PMID- 29350488
TI  - Fulminant adenovirus hepatitis with adenovirus-associated esophagitis
      complicating malignant lymphoma.

PMID- 29350489
TI  - Bioderived DNA Nanomachines for Potential Uses in Biosensing, Diagnostics, and
      Therapeutic Applications.
AB  - Beside its genomic properties, DNA is also recognized as a novel material in the
      field of nanoengineering. The specific bonding of base pairs can be used to
      direct the assembly of highly structured materials with specific nanoscale
      features such as periodic 2D arrays, 3D nanostructures, assembly of
      nanomaterials, and DNA nanomachines. In recent years, a variety of DNA
      nanomachines are developed because of their many potential applications in
      biosensing, diagnostics, and therapeutic applications. In this review, the fuel
      powered motors and secondary structure motors, whose working mechanisms are
      inspired or derived from natural phenomena and nanomachines, are discussed. The
      combination of DNA motors with other platforms is then discussed. In each section
      of these motors, their mechanisms and their usage in the biomedical field are
      described. Finally, it is believed that these DNA-based nanomachines and hybrid
      motifs will become an integral point-of-care diagnostics and smart, site-specific
      therapeutic delivery.

PMID- 29350490
TI  - Chronic exposure to high doses of selenium in the first trimester of pregnancy:
      Case report and brief literature review.
AB  - BACKGROUND: Obstetricians usually prescribe supplements during pregnancy without
      actual indication. The use of selenium during pregnancy has increased, due to its
      function in several antioxidant mechanisms. CASE: A pregnant woman received
      200,000 micrograms (MUg) per day of a selenium galenic formulation, since
      gestational week (g.w.) 7 to 12, due to a prescription error. The patient
      experienced nausea, vomiting, hand and foot paresthesia, followed by fatigue,
      loss of fingernails and hair. The woman was referred to our Fetal and Maternal
      Medicine Unit for surveillance. The mother's blood selenium levels went back to
      normal 13 weeks after arrest and the baby was born at term, without
      complications. Clinical evaluation and imaging studies were normal at one month
      of age. CONCLUSION: This is the first case of severe chronic selenium
      intoxication during the first trimester of pregnancy. In the present case, no
      consequences of congenital defects or pregnancy complications occurred. However,
      since vitamins, minerals, and food supplements may be harmful and prescription
      errors occur, obstetricians should avoid prescribing supplements in the absence
      of maternal deficiency.

PMID- 29350491
TI  - Reproductive toxic impact of subchronic treatment with combined butylparaben and
      triclosan in weanling male rats.
AB  - The effect of treatment with combined butylparaben and triclosan on male gonadal
      toxicity in weanling rats was investigated. All treated groups experienced
      atrophy in the ventral prostate and seminal vesicle, likewise significant
      depletion in the number and motility of sperm. Given individually or combined
      butylparaben and triclosan, significantly decreased testosterone, luteinizing
      hormone, and follicle-stimulating hormone levels. Individual treatment with
      tested compounds caused significant elevation in the E2 level, whereas combined
      treatment did not alter the E2 level. Testicular DNA damage was recorded in all
      treated groups. Moreover, the testicular malondialdehyde level was significantly
      elevated, along with a significant decrease in catalase enzyme activity in all
      treated groups. Superoxide dismutase enzyme activity was significantly decreased
      in the butylparaben-treated group, increased in the triclosan-treated group, and
      nonsignificantly changed the butylparaben-triclosan-treated group. The combined
      treatment produced an endocrine disturbance with a concomitant induction of
      testicular oxidative stress, which may represent a common mechanism of endocrine
      disruptor-mediated dysfunction.

PMID- 29350492
TI  - Clinical use of brain magnetic resonance imaging for neurological symptoms in
      people living with HIV.

PMID- 29350494
TI  - Sleep disruption in caregivers of pediatric stem cell recipients.
AB  - Parents/caregivers of hospitalized patients are at risk of sleep disruption. We
      performed a cross-sectional quantitative and qualitative evaluation of sleep in
      parents/caregivers of children undergoing hematopoietic stem cell transplant
      (HSCT; n = 17). Additionally, we explored the frequency of room entries for
      hospitalized patients undergoing HSCT (n = 189 nights). Twelve caregivers (71%)
      demonstrated significant sleep disturbance, 12 (71%) described sleep quality as
      poor, 15 (88%) averaged < 6 hours of sleep per night, 14 (82%) awakened at least
      four times per night. Patient rooms were entered a median of 12 times per night
      (interquartile range 10-15). Intervention studies to improve caregiver sleep
      during hospitalization are needed.

PMID- 29350493
TI  - Bleeding and thrombotic complications of pediatric liver transplant.
AB  - BACKGROUND: Pediatric patients undergoing liver transplant are at significant
      risk for bleeding and thrombotic complications due to the complex nature of
      rebalanced hemostasis in patients with liver disease. METHODS/OBJECTIVES: We
      reviewed records of 92 pediatric liver and multivisceral transplant cases at Duke
      University Medical Center between January 2009 and December 2015. The goal was to
      define the nature and incidence of bleeding and thrombotic complications in this
      cohort and define potential risk factors. RESULTS: There were 24 major bleeding
      events in 19 transplants (incidence 20.7%) and 30 thrombotic events in 23
      transplants (incidence 25%). Five of the 10 retransplantations were for vascular
      thrombotic complications. Thirty-day mortality was 4.9%, and three of these four
      deaths were due to vascular thrombosis. No bleeding events led to
      retransplantation or mortality. Prophylactic aspirin was associated with
      decreased risk of thrombosis without increased bleeding. Prophylactic heparin did
      not increase bleeding risk. Laboratory assays predicted events poorly, apparently
      failing to capture the nuanced and dynamic interplay between pro- and
      anticoagulant factors in the posttransplant patient. CONCLUSIONS: Both bleeding
      and thrombosis are frequent in this population, but only thrombotic complications
      contributed to retransplantation and mortality. A standardized approach to
      coagulation testing and antithrombotic therapy may be useful in predicting and
      reducing adverse outcomes. Alternative approaches to monitoring hemostasis need
      to be prospectively investigated in this complex patient population.

PMID- 29350495
TI  - The Current Landscape of 3D In Vitro Tumor Models: What Cancer Hallmarks Are
      Accessible for Drug Discovery?
AB  - Cancer prognosis remains a lottery dependent on cancer type, disease stage at
      diagnosis, and personal genetics. While investment in research is at an all-time
      high, new drugs are more likely to fail in clinical trials today than in the
      1970s. In this review, a summary of current survival statistics in North America
      is provided, followed by an overview of the modern drug discovery process,
      classes of models used throughout different stages, and challenges associated
      with drug development efficiency are highlighted. Then, an overview of the cancer
      hallmarks that drive clinical progression is provided, and the range of available
      clinical therapies within the context of these hallmarks is categorized.
      Specifically, it is found that historically, the development of therapies is
      limited to a subset of possible targets. This provides evidence for the
      opportunities offered by novel disease-relevant in vitro models that enable
      identification of novel targets that facilitate interactions between the tumor
      cells and their surrounding microenvironment. Next, an overview of the models
      currently reported in literature is provided, and the cancer biology they have
      been used to explore is highlighted. Finally, four priority areas are suggested
      for the field to accelerate adoption of in vitro tumour models for cancer drug
      discovery.

PMID- 29350496
TI  - Venoocclusive disease due to chemotherapy for pediatric acute lymphoblastic
      leukemia is associated with increased levels of plasminogen-activator inhibitor
      1.
AB  - We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease
      (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three
      episodes occurred during or just after the induction or reinduction phase of
      treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and
      pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and
      resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy.
      In all three episodes, the clinical diagnosis of SOS was associated with a
      significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced
      with patient clinical improvement. PAI-1 warrants study as a diagnostic marker
      for SOS in ALL.

PMID- 29350497
TI  - Sensitive and rapid determination of pyrethroids in human blood by gas
      chromatography-tandem mass spectrometry with ultrasound-assisted dispersive
      liquid-liquid microextraction.
AB  - In this study, a sensitive and fast procedure of ultrasonic-assisted dispersive
      liquid-liquid microextraction (UADLLME) coupled with gas chromatography-tandem
      mass spectrometry (GC-MS/MS) for the determination of major pyrethroid pesticides
      (permethrin, tetramethrin, bifenthrin, fenvalerate, flucythrinate, fluvalinate,
      fenpropathrin, deltamethrin, and cyhalothrin) in blood samples was developed.
      Response surface methodology (RSM) combined with Box-Behnken design (BBD) and
      ANOVA function was used to optimize key factors affecting the extraction
      efficiency of UADLLME procedure. Target compounds were analyzed by GC-MS/MS.
      Under the optimal conditions, good linearity (R2 >0.99) was achieved for all the
      analytes in the concentration range of 0.5 to 100 MUg L-1 . The recoveries for
      spiked samples at 3 concentration levels were between 70.2 and 91.8%, with
      relative standard deviations (RSD) lower than 10%. Very low limits of detection
      (LODs) and limits of quantification (LOQs) ranging from 0.01 to 0.1 MUg L-1 and
      from 0.03 to 0.3 MUg L-1 were achieved. This method was successfully applied to
      the determination of low concentration of pyrethroids in blood samples from real
      forensic cases. High sensitivity, fast determination, simplicity in operation,
      small sample volume, and low usage of organic solvents are the advantages of this
      method. This methodology is of important value for sensitive and quick
      determination of residue pesticides and metabolites, study of residue pesticides
      behavior in human body, as well as application in real forensic cases.

PMID- 29350498
TI  - Glioma-Targeted Delivery of a Theranostic Liposome Integrated with Quantum Dots,
      Superparamagnetic Iron Oxide, and Cilengitide for Dual-Imaging Guiding Cancer
      Surgery.
AB  - Herein, a theranostic liposome (QSC-Lip) integrated with superparamagnetic iron
      oxide nanoparticles (SPIONs) and quantum dots (QDs) and cilengitide (CGT) into
      one platform is constructed to target glioma under magnetic targeting (MT) for
      guiding surgical resection of glioma. Transmission electron microscopy and X-ray
      photoelectron spectroscopy confirm the complete coencapsulation of SPIONs and QDs
      in liposome. Besides, CGT is also effectively encapsulated into the liposome with
      an encapsulation efficiency of ~88.9%. QSC-Lip exhibits a diameter of 100 +/-
      1.24 nm, zeta potential of -17.10 +/- 0.11 mV, and good stability in several
      mediums. Moreover, each cargo shows a biphasic release pattern from QSC-Lip, a
      rapid initial release within initial 10 h followed by a sustained release.
      Cellular uptake of QSC-Lip is significantly enhanced by C6 cells under MT. In
      vivo dual-imaging studies show that QSC-Lip not only produces an obvious negative
      contrast enhancement effect on glioma by magnetic resonance imaging but also
      makes tumor emitting fluorescence under MT. The dual-imaging of QSC-Lip guides
      the accurate resection of glioma by surgery. Besides, CGT is also specifically
      distributed to glioma after administration of QSC-Lip under MT, resulting in an
      effective inhibition of tumors. The integrated liposome may be a potential
      carrier for theranostics of tumor.

PMID- 29350499
TI  - The importance of developing atherosclerosis in pseudoexfoliation glaucoma.
AB  - Background/Aim: Pseudoexfoliation syndrome (XPS) is an age-related systemic
      disorder characterized by increased production and accumulation of elastic
      microfibrillar material in different tissues of the body: skin, connective tissue
      portions of visceral organs, periphery blood vessels and the eye, as well. The
      aim of our study was to determine the significance of atherosclerotic changes in
      the carotid arteries in the development of XFS and pseudoexfoliation glaucoma
      (XFG). Methods: The study included 120 patients - 40 patients per each of the
      three defined groups: XFS group, XFG group and age- and sex-matched control
      subjects (control group) without XFG. Blood samples were collected from the
      patients before cataract surgery. Serum levels of total cholesterol, low-density
      lipoprotein - LDL, high density lipoprotein - HDL and triglycerides were analyzed
      by standard laboratory techniques. Standard ultrasonography of the carotid blood
      vessels was performed in all the participants. Results: Lipid's profile was
      disturbed in the patients with XFS and XFG with statistical significance p
      control group (p < 0.01). Systolic and diastolic pressure was elevated in the
      patients with XFS and XFG (p < 0.01). Resistance index was increased in the
      patients with XFG (p < 0.01). Intima-media thickness was prolonged in patients
      with XFG (p < 0.01). Conclusion: A disturbed lipid profile with elevated
      resistancy index and intima-media thickness and increased systolic and diastolic
      pressure were compulsory findings in patients with developed XFG. So, these
      factors could be considered as risk. It seems to be difficult to inhibit the
      process of pseudoexfolation production in the whole body, but it appears that
      with proper therapy (antihypertnesive, cardiotoncs, etc.) and adequate
      nourishing, the process of XFG development could be interrupted.

PMID- 29350500
TI  - Global Advisory Committee on Vaccine Safety, 6-7 December 2017.

PMID- 29350501
TI  - Creatinine-modified Child-Turcotte-Pugh score is a good predictor of a short-term
      survival in patients with bleeding from esophageal varices.
AB  - Background/Aim: Bleeding from esophageal varices is a significant factor in
      mortality of patients with terminal liver cirrhosis. This complication is a major
      health problem for recipients on the list for liver transplant. In that regard,
      studying predictors of variceal bleeding episode is very important. Also, it is
      important to find the best survival predictor among prognostic scores. The aim of
      the study was to compare validity of prognostic scores in assessment of survival
      in hospital-treated patients after bleeding from esophageal varices, and to
      compare validity of baseline Child-Turcotte-Pugh (CTP) and Modul for End-stage
      Liver Disease (MELD) scores with CTP creatinine modified (CTP-crea) I and II
      scores in assessment of survival in patients within a long-term follow-up period
      after the episode of bleeding from esophageal varices. Methods: The study
      included a total of 126 patients suffering from terminal liver cirrhosis submited
      to testing CTP score score I and II, MELD score, MELD Na score, integrated MELD
      score, MELD sodium (MESO) index, United Kingdom Model for End-Stage Liver Disease
      (UKELD) score and updated MELD score. Results: Patients with bleeding from
      esophageal varices most often had CTP score rank C (46,9%). CTP score rank B had
      37.5% patients, while the smallest percentage of patients had CTP rank A, 15.6%
      of them. Patients who have values of CTP score higher than 10.50 and bleeding
      from esophagus, have 3.2 times higher chance for death outcome compared to other
      patients. Patients who have values of CTP-crea I score higher than 10.50 and
      bleeding from esophagus, have 3.1 times higher chance for death out-come than
      other patients. Patients who have values of CTP-crea II score higher than 11.50
      and bleeding from esophagus, have 3,7 times higher chance for death outcome
      compared to other patients. Conclusion: Survival of patients with bleeding from
      esophageal varices in the short-term follow up can be predicted by following CTP
      score and creatinine modified CTP scores. Patients with bleeding from esophageal
      varices who have CTP score and CTP-crea I score higher than 10.5 and CTP-crea II
      score higher than 11.5, have statistically significantly higher risk from
      mortality within one-month follow-up compared to patients with bleeding from
      esophageal varices who have lower numerical values of scores of the CTP group.

PMID- 29350502
TI  - The influence of Dupuytren's disease fingers contracture degree on surgical
      treatment outcome.
AB  - Background/Aim: Dupuytren's disease is a progressive disease of the palmar and
      digital fascial structures, with functional limitations. There are no clear
      recommendations about the optimal time of surgical repair, concerning the hand
      impairment. The aim of our study was to investigate the relation between finger's
      contracture degree and success of surgical treatment of the Dupuytren's disease.
      Methods: This prospective analysis included 60 patients operated on due to
      Dupuytren's contracture. According to preoperative contracture degree of proximal
      interphalangeal (PIP) and metacarpophalangeal (MCP) joint, patients were divided
      into three groups: the group 1: < 15 degrees , the group 2: 15-30 degrees  and
      the group 3: > 30 degrees . All the patients underwent operation of partial
      palmar fasciectomy. Postoperative improvement was expressed with contracture
      reduction INDEX. Results: There were 60 patients with 85 fingers affected. The
      groups 1, 2 and 3 had 22 (37%), 37 (62%) and 26 (43%) fingers with MCP
      contracture and 32 (37.4%), 24 (28.2%) and 29 (34.1%) fingers with PIP
      contracture, respectively. Postoperative contractures of MCP joint in these
      groups were 0, 0.135 degrees  and 5 degrees , and of PIP joint 0, 2.08  degrees 
      and 16.89 degrees , respectively. After six months all MCP contractures resolved,
      while PIP joint contracture in the group 3 remained 13.62 degrees . The reduction
      INDEX was 98.85%, 97.62% and 75.52% in the groups 1, 2 and 3, respectively. There
      was a statistically significant difference in the INDEX value between the groups
      (p = 0.0001). Conclusion: The degree of PIP joint contracture is related to the
      outcome of surgical treatment of Dupuytren's disease. Optimal results are
      achieved when contracture degree is between 15 degrees  and 30 degrees . Surgical
      treatment of MCP joint contracture is successful regardless of the preoperative
      joint contracture degree.

PMID- 29350503
TI  - Presence of histopathological premalignant lesions and infection caused by high
      risk genotypes of human papillomavirus in patients with suspicious cytological
      and colposcopy results: A prospective study.
AB  - Background/Aim: In patients with premalignant cervical lesions, human
      papillomavirus (HPV) infection, at any moment, may be spontaneously eliminated,
      or may persist or transform cervical epithelium from a lower to a higher degree.
      Due to that, it is necessary to wisely select the patients who are at high risk
      of cancer development. The aim of the study was to establish the interdependence
      between a suspicious Papanicolaou (Pap) test and colposcopy with the infection
      caused by high-risk genotypes of human papillomavirus and the presence of
      premalignant cervical lesions. Methods: This prospective study used cytological,
      colposcopy, real-time polymerase chain reaction (PCR) of high-risk genotypes of
      human papillomavirus and histopathological analysis of cervical biopsy specimen.
      Out of 2,578 female patients sent to cytological analyses in Clinical Center of
      Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to
      submit their biopsy specimens due to a suspicious Pap test and atypical
      colposcopy results. Results: In the group of 80 (3.1%; n = 80/2,578) of the
      selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70%)
      of them had cervicitis, and 1/3 or 24 (30%) had cervical intraepithelial
      neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16
      in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of
      the total number of premalignant lesions Conclusion: Patients with suspicious
      Papanicolaou test, colposcopy results and infection which is caused by high-risk
      HPV infection (HPV 16 in particular) often have premalignant cervical lesions. In
      these cases, histopathological confirmation of lesions is mandatory, since it
      serves as a definitive diagnostic procedure.

PMID- 29350504
TI  - Age-related changes of superoxide dismutase activity in patients with
      schizophrenia.
AB  - Background/Aim: Superoxide dismutase (SOD) is the critical enzyme in the
      detoxification of superoxide radicals because those are the first species
      produced in the majority of biological free radical producing reactions.
      Inconsistent data are present about SOD activity in patients with schizophrenia.
      Numerous studies have shown that SOD has been elevated in chronic schizophrenic
      patients. However, decreased SOD activity was found in neuroleptic naive, first
      episode schizophrenic patients, in chronic-medicated patients and in chronic
      unmedicated patients. The aim of this study was to examine which of the following
      factors including age, gender, the onset of the disease, the duration, the number
      of episodes, heredity, psychopathologic symptoms and drug treatment could affect
      erythrocyte SOD activity in patients with schizophrenia. Methods: This study
      included 68 consecutive patients with schizophrenia (29 males and 39 females)
      ranging in age from 18 to 61 years, divided into two age groups (<34 years and
      >34 years). SOD activity was measured in erythrocyte hemolyzates by Ransod
      commercially available test. Results: In the group of patients younger than 34
      years SOD levels were significantly higher (1381+/-273 U/gHb, p=0.038) compared
      to the levels of the older group (1231+/-206 U/gHb). Gender and heredity did not
      induce any significant difference in SOD activity between younger and older
      subgroups. A significant difference in enzyme activity was found between the
      younger and older subgroups having the onset of the disease after 24 years of age
      (1408+/-217 U/gHb vs. 1252+/-213 U/gHb, p=0.031). The patients of the younger
      group who had more than one psychotic episode had significantly higher SOD
      activity (1492+/-298 U/gHb; p=0.009) than those who had only one episode (1256+/
      177 U/gHb), as well as than the older subgroup with more than one episode (1253+/
      231 U/gHb; p=0.014). Although the duration of the disease did not induce any
      significant difference in enzyme activity between younger and older subgroups, a
      significant negative correlation was obtained between SOD activity and the
      duration of the disease (r=-0.511, p<0.01). No significant differences were found
      in SOD activity between the subgroups with different PANSS scores. First
      generation antipsychotics were associated with elevated enzyme activity in both
      groups. Simultaneous treatment of patients with first generation antipsychotics
      and second generation antipsychotics induced a significant decrease in SOD
      activity in the younger group. Conclusion: Our results show that erythrocyte SOD
      activity is increased in the early phase of schizophrenia and that depends on age
      of onset of the disease, the number of psychotic episodes, the duration of the
      disease and medical treatment.

PMID- 29350505
TI  - Bridging the digital divide: mobile access to personal health records among
      patients with diabetes.
AB  - OBJECTIVES: Some patients lack regular computer access and experience a digital
      divide that causes them to miss internet-based health innovations. The diffusion
      of smartphones has increased internet access across the socioeconomic spectrum,
      and increasing the channels through which patients can access their personal
      health records (PHRs) could help bridge the divide in PHR use. We examined PHR
      use through a computer-based Web browser or mobile device. STUDY DESIGN: Cross
      sectional historical cohort analysis. METHODS: Among adult patients in the
      diabetes registry of an integrated healthcare delivery system, we studied the
      devices used to access their PHR during 2016. RESULTS: Among 267,208 patients
      with diabetes, 68.1% used the PHR in 2016; 60.6% of all log-ins were via computer
      and 39.4% were via mobile device. Overall, 63.9% used it from both a computer and
      mobile device, 29.6% used only a computer, and 6.5% used only a mobile device.
      After adjustment, patients who were black, Hispanic, or Asian; lived in lower
      socioeconomic status (SES) neighborhoods; or had lower engagement were all
      significantly more likely to use the PHR only from a mobile device (P <.05).
      Patients using the PHR only via mobile device used it less frequently.
      CONCLUSIONS: Mobile-ready PHRs may increase access among patients facing a
      digital divide in computer use, disproportionately reaching racial/ethnic
      minorities and lower SES patients. Nonetheless, even with a mobile-optimized and
      app-accessible PHR, differences in PHR use by race/ethnicity and SES remain.
      Continued efforts are needed to increase equitable access to PHRs among patients
      with chronic conditions.

PMID- 29350506
TI  - Electronic health record "super-users" and "under-users" in ambulatory care
      practices.
AB  - OBJECTIVES: This study explored variation in the extent of use of electronic
      health record (EHR)-based health information technology (IT) functionalities
      across US ambulatory care practices. Use of health IT functionalities in
      ambulatory care is important for delivering high-quality care, including that
      provided in coordination with multiple practitioners. STUDY DESIGN: We used data
      from the 2014 Healthcare Information and Management Systems Society Analytics
      survey. The responses of 30,123 ambulatory practices with an operational EHR were
      analyzed to examine the extent of use of EHR-based health IT functionalities for
      each practice. METHODS: We created a novel framework for classifying ambulatory
      care practices employing 7 domains of health IT functionality. Drawing from the
      survey responses, we created a composite "use" variable indicating the extent of
      health IT functionality use across these domains. "Super-user" practices were
      defined as having near-full employment of the 7 domains of health IT
      functionalities and "under-users" as those with minimal or no use of health IT
      functionalities. We used multivariable logistic regression to investigate how the
      odds of super-use and under-use varied by practice size, type, urban or rural
      location, and geographic region. RESULTS: Seventy-three percent of practices were
      not using EHR technologies to their full capability, and nearly 40% were
      classified as under-users. Under-user practices were more likely to be of smaller
      size, situated in the West, and located outside a metropolitan area. CONCLUSIONS:
      To achieve the broader benefits of the EHR and health IT, health systems and
      policy makers need to identify and address barriers to full use of health IT
      functionalities.

PMID- 29350507
TI  - Hospital participation in Meaningful Use and racial disparities in readmissions.
AB  - OBJECTIVES: To measure the impact of hospital participation in Meaningful Use
      (MU) on disparities in 30-day readmissions associated with race. STUDY DESIGN: A
      retrospective cohort study that compared the likelihood of 30-day readmission for
      Medicare beneficiaries discharged from hospitals participating in Stage 1 of MU
      with the likelihood of readmission for beneficiaries concurrently discharged from
      hospitals that were not participating in the initiative. METHODS: Inpatient
      claims for 2,414,205 Medicare beneficiaries from Florida, New York, and
      Washington State were used as the primary data source. The study period (2009
      2013) included at least 2 years of baseline data prior to each hospital
      initiating participation in MU. Estimates were derived with linear regression
      models that included hospital and time fixed effects. By including both hospital
      and time fixed effects, estimates were based on discharges from the same hospital
      in the same time period. RESULTS: MU participation among hospitals was not
      associated with a statistically significant change in readmissions for the
      broader Medicare population (percentage points [PP], 0.6; 95% CI, -0.2 to 1.4),
      but hospitals' participation in the initiative was associated with a lower
      likelihood of readmission for African American beneficiaries (PP, -0.9; 95% CI, 
      1.5 to -0.4). CONCLUSIONS: Hospital participation in MU reduced disparities in 30
      day readmissions for African American Medicare beneficiaries.

PMID- 29350508
TI  - The health information technology special issue: has IT become a mandatory part
      of health and healthcare?
AB  - The 7th annual Health Information Technology (IT) issue provides a window into
      how health IT tools are working well, how they may not be working as intended,
      and what we can do to continue making progress toward optimal use of technology
      to accomplish our shared goals: better health, better care experience, and lower
      per capita cost.

PMID- 29350509
TI  - Measuring overuse with electronic health records data.
AB  - OBJECTIVES: To measure overuse of low-value care using electronic health record
      (EHR) data and manual chart review and to evaluate whether certain low-value
      services are better captured using EHR data. STUDY DESIGN: We implemented
      algorithms to extract performance on 13 Choosing Wisely-identified healthcare
      services using EHR data at a large physician practice group between 2011 and
      2013. METHODS: We calculated rates of overuse using automated EHR extracts. We
      manually reviewed the charts for 200 cases of overuse for each measure to
      determine if they had clinical risk factors that could explain use of the low
      value service and then calculated adjusted rates of overuse. We explored trends
      in overuse for each low-value service in the 3-year duration using logistic
      regression. RESULTS: Unadjusted rates of overuse ranged from 0.2% to 92%.
      Automated EHR extracts and manual chart review identified explanatory risk
      factors for most measures, although the magnitude varied: for some measures (eg,
      bone densitometry exam for women younger than 65 years), manual chart review did
      not identify many additional risks (3.0%). In contrast, in patients who had sinus
      computed tomography or an antibiotic prescription for uncomplicated acute
      rhinosinusitis, manual chart review identified more explanatory risk factors
      (22.5%) than the automated EHR extract (9.5%). Adjusted rates of overuse ranged
      from 0.2% to 61.9%. Eight services demonstrated a statistically significant
      decrease in overuse over 3 years, while 1 increased significantly. CONCLUSIONS:
      The use of EHR data, both extracted and manually abstracted, provides an
      opportunity to more accurately and reliably identify overuse of low-value
      healthcare services.

PMID- 29350510
TI  - Electronic sharing of diagnostic information and patient outcomes.
AB  - OBJECTIVES: Hospital sharing of electronic health record (EHR) diagnostic data
      has the potential to improve communication across providers and improve patient
      outcomes. However, implementing EHR systems can be difficult for hospitals. This
      study uses Hospital Compare (HC) and American Hospital Association (AHA) Annual
      Information Technology Survey data to estimate the association between sharing
      EHR data and patient outcomes. STUDY DESIGN: Descriptive and multivariate linear
      regression analyses. METHODS: This study links 2 years of HC data on 30-day
      patient mortality and readmissions for heart failure (HF) and pneumonia with 2
      years of AHA data. The sample was restricted to hospitals included in both years
      in both sets of data. We estimated the associations between sharing EHR
      diagnostic data and patient outcomes with a multivariate linear regression
      analysis. Results were adjusted by hospital characteristics from the AHA annual
      survey. RESULTS: Hospitals' sharing of radiology report data with hospitals
      within their system was associated with significantly lower mortality scores for
      pneumonia (-0.22; P <.01). Conversely, hospital sharing of radiology report data
      with hospitals outside their system was associated with significantly higher HF
      mortality scores (0.26; P <.01). We found qualitatively similar results with
      sharing laboratory results through EHRs. CONCLUSIONS: Hospital sharing of EHR
      data with providers within their system is associated with better patient
      mortality, whereas sharing data with providers outside their system is associated
      with worsened patient mortality. Improving communication between hospitals using
      different EHR systems may be more crucial than simply expanding data sharing.

PMID- 29350511
TI  - A cost-effectiveness analysis of cardiology eConsults for Medicaid patients.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of electronic consultations
      (eConsults) for cardiology compared with traditional face-to-face consults. STUDY
      DESIGN: Cost-effectiveness analysis for a subset of Medicaid-insured patients in
      a cluster-randomized trial of eConsults versus the traditional face-to-face
      consultation process in a statewide federally qualified health center. METHODS: A
      total of 369 Medicaid patients were referred for cardiology consultations by
      primary care providers who were randomly assigned to use either eConsults or
      their usual face-to-face referral process. Primary care providers in the eConsult
      arm transmitted consults to cardiologists using a secure peer-to-peer
      communication platform in an electronic health record. Intention-to-treat
      analysis was used to assess the total cost of care and cost across 7 categories:
      inpatient, outpatient, emergency department, pharmacy, labs, cardiac procedures,
      and "all other." Costs are from the payer's perspective. RESULTS: Six months
      after the cardiology consult, patients in the eConsult group had significantly
      lower mean unadjusted total costs by $655 per patient, or lower mean costs by
      $466 per patient when adjusted for non-normality, compared with those in the face
      to-face arm. The eConsult group had a significantly lower cost by $81 per patient
      in the outpatient cardiac procedures category. CONCLUSIONS: These findings
      suggest that eConsults are associated with total cost savings to payers due
      principally to reductions in the cost of cardiac outpatient procedures.

PMID- 29350512
TI  - Electronic health record problem lists: accurate enough for risk adjustment?
AB  - OBJECTIVES: To determine whether comorbidity information derived from electronic
      health record (EHR) problem lists is accurate. STUDY DESIGN: Retrospective cohort
      study of 1596 men diagnosed with prostate cancer between 1998 and 2004 at 2
      Southern California Veterans Affairs Medical Centers with long-term follow-up.
      METHODS: We compared EHR problem list-based comorbidity assessment with manual
      review of EHR free-text notes in terms of sensitivity and specificity for
      identification of major comorbidities and Charlson Comorbidity Index (CCI)
      scores. We then compared EHR-based CCI scores with free-text-based CCI scores in
      prediction of long-term mortality. RESULTS: EHR problem list-based comorbidity
      assessment had poor sensitivity for detecting major comorbidities: myocardial
      infarction (8%), cerebrovascular disease (32%), diabetes (46%), chronic
      obstructive pulmonary disease (42%), peripheral vascular disease (31%), liver
      disease (1%), and congestive heart failure (23%). Specificity was above 94% for
      all comorbidities. Free-text-based CCI scores were predictive of long-term other
      cause mortality, whereas EHR problem list-based scores were not. CONCLUSIONS:
      Inaccuracies in EHR problem list-based comorbidity data can lead to incorrect
      determinations of case mix. Such data should be validated prior to application to
      risk adjustment.

PMID- 29350513
TI  - Racial/ethnic variation in devices used to access patient portals.
AB  - OBJECTIVES: We examined racial/ethnic variation in the devices used by patients
      to access medical records through an online patient portal. STUDY DESIGN:
      Retrospective, cross-sectional analysis. METHODS: Using data from 318,700 adults
      enrolled in an integrated delivery system between December 2012 and November
      2013, we examined: 1) online patient portal use that directly engages the
      electronic health record and 2) portal use over desktops/laptops only, mobile
      devices only, or both device types. The primary covariate was race/ethnicity (non
      Hispanic white, black, Hispanic, and Asian). Other covariates included age, sex,
      primary language, and neighborhood-level income and education. Portal use and
      devices used were assessed with multiple and multinomial logistic models,
      respectively. RESULTS: From December 2012 to November 2013, 56% of enrollees used
      the patient portal. Of these portal users, 62% used desktops/laptops only, 6%
      used mobile devices only, and 32% used both desktops/laptops and mobile devices.
      Black, Hispanic, and Asian enrollees had significantly lower odds of portal use
      than whites. Black and Hispanic portal users also were significantly more likely
      to use mobile devices only (relative risk ratio, 1.73 and 1.44, respectively) and
      both device types (1.21 and 1.07, respectively) than desktops/laptops only
      compared with whites. CONCLUSIONS: Although racial/ethnic minority enrollees were
      less likely to access the online patient portal overall, a greater proportion of
      black and Hispanic users accessed the patient portal with mobile devices than did
      non-Hispanic white users. The rapid spread of mobile devices among racial/ethnic
      minorities may help reduce variation in online patient portal use. Mobile device
      use may represent an opportunity for healthcare organizations to further engage
      black and Hispanic enrollees in online patient portal use.

PMID- 29350514
TI  - Hospitalized patients' and family members' preferences for real-time, transparent
      access to their hospital records.
AB  - OBJECTIVES: To better understand patient satisfaction and perceived engagement
      with traditional hospital-based communication and to elicit patient preferences
      for health information technologies that would lead to improved satisfaction and
      engagement. STUDY DESIGN: We performed a mixed-methods study involving
      qualitative interviews followed by a survey of hospitalized patients and their
      family members at a single large academic medical center. METHODS: We conducted
      semi-structured interviews with 41 patients and surveyed 267 patients or family
      members to elicit their perspectives on satisfaction with traditional hospital
      communication methods, information needed to more fully engage in the patients'
      medical care, and potential solutions for improved hospital-based communication.
      RESULTS: Qualitative interviews revealed patients' and family members'
      dissatisfaction with current hospital-based communication methods. They would
      prefer more information, in more flexible forms, with real-time digital access
      and the ability to share within their social and healthcare networks.
      Quantitative results from the survey supported these premises, with at least the
      majority of the 267 patients surveyed agreeing across each survey question.
      Furthermore, participants identified a "communications point person" as the
      individual who organizes, understands, and communicates about the patient's care,
      who was often a family member not available at the bedside during daily rounds.
      Potential solutions included improved transparency about hospital processes,
      creating systems that allow patients and family to help coordinate and double
      check their own health-related communications, and delivering hospital-based
      communications through digital media. CONCLUSIONS: These study findings provide
      empiric evidence to hospital decision-makers regarding patient and family
      preferences for 21st-century hospital-based communication systems.

PMID- 29350515
TI  - Rapid One-Pot Microwave Synthesis of Mixed-Linker Hybrid Zeolitic-Imidazolate
      Framework Membranes for Tunable Gas Separations.
AB  - The relatively slow and complex fabrication processes of polycrystalline metal
      organic framework (MOF) membranes often times restrict their way to
      commercialization, despite their potential for molecular separation applications.
      Herein, we report a rapid one-pot microwave synthesis of mixed-linker hybrid
      zeolitic-imidazolate framework (ZIF) membranes consisting of 2-methylimidazolate
      (ZIF-8 linker) and benzimidazolate (ZIF-7 linker) linkers, termed ZIF-7-8
      membranes. The fast-volumetric microwave heating in conjunction with a unique
      counter diffusion of metal and linker solutions enabled unprecedented rapid
      synthesis of well-intergrown ZIF-7-8 membranes in ~90 s, the fastest MOF membrane
      preparation up to date. Furthermore, we were able to tune the molecular sieving
      properties of the ZIF-7-8 membranes by varying the benzimidazole-to-2
      methylimidazole (bIm-to-mIm) linker ratio in the hybrid frameworks. The tuning of
      their molecular sieving properties led to the systematic change in the permeance
      and selectivity of various small gases. The unprecedented rapid synthesis of well
      intergrown ZIF-7-8 membranes with tunable molecular sieving properties is an
      important step forward for the commercial gas separation applications of ZIF
      membranes.

PMID- 29350516
TI  - Time-Dependent Density Functional Theory for Open Systems and Its Applications.
AB  - Photovoltaic devices, electrochemical cells, catalysis processes, light emitting
      diodes, scanning tunneling microscopes, molecular electronics, and related
      devices have one thing in common: open quantum systems where energy and matter
      are not conserved. Traditionally quantum chemistry is confined to isolated and
      closed systems, while quantum dissipation theory studies open quantum systems.
      The key quantity in quantum dissipation theory is the reduced system density
      matrix. As the reduced system density matrix is an O(M! * M!) matrix, where M is
      the number of the particles of the system of interest, quantum dissipation theory
      can only be employed to simulate systems of a few particles or degrees of
      freedom. It is thus important to combine quantum chemistry and quantum
      dissipation theory so that realistic open quantum systems can be simulated from
      first-principles. We have developed a first-principles method to simulate the
      dynamics of open electronic systems, the time-dependent density functional theory
      for open systems (TDDFT-OS). Instead of the reduced system density matrix, the
      key quantity is the reduced single-electron density matrix, which is an N * N
      matrix where N is the number of the atomic bases of the system of interest. As
      the dimension of the key quantity is drastically reduced, the TDDFT-OS can thus
      be used to simulate the dynamics of realistic open electronic systems and
      efficient numerical algorithms have been developed. As an application, we apply
      the method to study how quantum interference develops in a molecular transistor
      in time domain. We include electron-phonon interaction in our simulation and show
      that quantum interference in the given system is robust against nuclear vibration
      not only in the steady state but also in the transient dynamics. As another
      application, by combining TDDFT-OS with Ehrenfest dynamics, we study current
      induced dissociation of water molecules under scanning tunneling microscopy and
      follow its time dependent dynamics. Given the rapid development in ultrafast
      experiments with atomic resolution in recent years, time dependent simulation of
      open electronic systems will be useful to gain insight and understanding of such
      experiments. This Account will mainly focus on the practical aspects of the TDDFT
      OS method, describing the numerical implementation and demonstrating the method
      with applications.

PMID- 29350517
TI  - Cellphone-Enabled Microwell-Based Microbead Aggregation Assay for Portable
      Biomarker Detection.
AB  - Quantitative biomarker detection methods featured with rapidity, high accuracy,
      and label-free are demonstrated for the development of point-of-care (POC)
      technologies or "beside" diagnostics. Microbead aggregation via protein-specific
      linkage provides an effective approach for selective capture of biomarkers from
      the samples, and can directly readout the presence and amount of the targets.
      However, sensors or microfluidic analyzers that can accurately quantify the
      microbead aggregation are scared. In this work, we demonstrate a microwell-based
      microbeads analyzing system, by which online manipulations of microbeads
      including trapping, arraying, and rotations can be realized, providing a series
      of microfluidic approaches to layout the aggregated microbeads for further
      convenient characterizations. Prostate specific antigen is detected using the
      proposed system, demonstrating the limit of detection as low as 0.125 ng/mL (3.67
      pM). A two-step reaction kinetics model is proposed for the first time to explain
      the dynamic process of microbeads aggregation. The developed microbeads
      aggregation analysis system has the advantages of label-free detection, high
      throughput, and low cost, showing great potential for portable biomarker
      detection.

PMID- 29350518
TI  - Development of Self-Healing d-Gluconic Acetal-Based Supramolecular Ionogels for
      Potential Use as Smart Quasisolid Electrochemical Materials.
AB  - Formation of supramolecular ionic liquid (IL) gels (ionogels) induced by low
      molecular-mass gelators (LMMGs) is an efficient strategy to confine ILs, and the
      negligible influence of LMMGs on the electrochemical properties of ILs makes
      ionogels ideal quasisolid electrochemical materials. Furthermore, the stimuli
      responsive and self-healing characters of the supramolecular gel can be utilized
      for the potential development of smart electrochemical materials. However, the
      poor mechanical properties of supramolecular ionogels reported so far limit their
      practical applications. Herein, we investigated a series of efficient d-gluconic
      acetal-based gelators (Gn, PG16, and B8) that can harden a wide variety of ILs at
      low concentrations. It was shown that both alkyl chain length and the number of
      hydrogen bonding sites of a certain gelator, as well as the nature of the IL
      anion, significantly influenced the gelation abilities. The resulting ionogels
      were thermally reversible, and most of them were stable at room temperature.
      Interestingly, a PG16-based supramolecular ionogel showed rapid self-healing
      properties upon mechanical damage. Furthermore, the PG16-based ionogel
      demonstrated unprecedented performances including the favorable ionic
      conductivity, excellent mechanical strength, and enhanced viscoelasticity, which
      make it a great self-healing electrochemical material. The ionogel formation
      mechanism was proposed based on the analysis of Fourier transform infrared,
      1HNMR, and X-ray diffraction, indicating that a combination of hydrogen bonding,
      pi-pi stacking, and interactions between alkyl chains was responsible for the
      self-assembly of gelators in ILs. Overall, our present studies on exploring the
      structure-property relationship of gelators for the formation of practically
      useful supramolecular ionogels shed light for future development of more
      functionalized ionogels.

PMID- 29350519
TI  - Surface Functionalization for a Nontextured Liquid-Infused Surface with Enhanced
      Lifetime.
AB  - Liquid-infused surfaces (LISs) are a new class of self-cleaning surfaces having
      superior properties compared to other self-cleaning surfaces. One challenge
      regarding these is the eventual washing away or drainage of the lubricant,
      limiting their longevity. Presented here is a surface functionalization strategy
      to compatibilize the lubricant and surface, enhancing the ability of the
      lubricant to remain on the surface even during washing. The strategy used here is
      the grafting of a layer of polydimethylsiloxane (PDMS) to the surface, which
      stabilizes a layer of silicone oil. The effectiveness of this layer is studied as
      a function of PDMS molecular weight. The stable liquid layer can exist even in
      the absence of texture on the surface that is generally used to "lock" the
      lubricant in place. This strategy is shown to be effective on both flat and
      textured surfaces. One advantage of a flat surface is that the composite
      liquid/solid surface can be studied using optical techniques such as
      ellipsometry, which are difficult to employ in the presence of a rough solid
      surface. This method of surface compatibilization shows an enhanced lifetime when
      used on textured surfaces as well. This is a promising strategy for the enhanced
      longevity of LISs required for real-world applications.

PMID- 29350520
TI  - One-Step Synthesis of Co-Doped In2O3 Nanorods for High Response of Formaldehyde
      Sensor at Low Temperature.
AB  - Uniform and monodisperse Co-doped In2O3 nanorods were fabricated by a facile and
      environmentally friendly hydrothermal strategy that combined the subsequent
      annealing process, and their morphology, structure, and formaldehyde (HCHO) gas
      sensing performance were investigated systematically. Both pure and Co-doped
      In2O3 nanorods had a high specific surface area, which could offer abundant
      reaction sites to gas molecular diffusion and improve the response of the gas
      sensor. Results revealed that the In2O3/1%Co nanorods exhibited a higher response
      of 23.2 for 10 ppm of HCHO than that of the pure In2O3 nanorods by 4.5 times at
      130  degrees C. More importantly, the In2O3/1%Co nanorods also presented
      outstanding selectivity and long-term stability. The superior gas sensing
      properties were mainly attributed to the incorporation of Co, which suggested the
      important role of the amount of oxygen vacancies and adsorbed oxygen in enhancing
      HCHO sensing performance of In2O3 sensors.

PMID- 29350521
TI  - Facile and Highly Effective Synthesis of Controllable Lattice Sulfur-Doped
      Graphene Quantum Dots via Hydrothermal Treatment of Durian.
AB  - Recently, the biomass "bottom-up" approach for the synthesis of graphene quantum
      dots (GQDs) has attracted broad interest because of the outstanding features,
      including low-cost, rapid, and environmentally friendly nature. However, the low
      crystalline quality of products, substitutional doping with heteroatoms in
      lattice, and ambiguous reaction mechanism strongly challenge the further
      development of this technique. Herein, we proposed a facile and effective
      strategy to prepare controllable sulfur (S) doping in GQDs, occurring in a
      lattice substitution manner, by hydrothermal treatment of durian with platinum
      catalyst. S atoms in GQDs are demonstrated to exist in the thiophene structure,
      resulting in good optical and chemical stabilities, as well as ultrahigh quantum
      yield. Detailed mechanism of the hydrothermal reaction progress was investigated.
      High-efficiency reforming cyclization provided by platinum was evidenced by the
      coexistence of diversified sp2-fused heterocyclic compounds and thiophene
      derivatives. Moreover, we also demonstrated that saccharides in durian with small
      molecular weight (<1000 Da) is the main carbon source for the forming GQDs.
      Because of the desulfurizing process, controllable photoluminescence properties
      could be achieved in the as-prepared GQDs via tuning doping concentrations.

PMID- 29350522
TI  - Chemical Design of Both a Glutathione-Sensitive Dimeric Drug Guest and a Glucose
      Derived Nanocarrier Host to Achieve Enhanced Osteosarcoma Lung Metastatic
      Anticancer Selectivity.
AB  - Although nanomedicines have been pursued for nearly 20 years, fundamental
      chemical strategies that seek to optimize both the drug and drug carrier together
      in a concerted effort remain uncommon yet may be powerful. In this work, two
      block polymers and one dimeric prodrug molecule were designed to be coassembled
      into degradable, functional nanocarriers, where the chemistry of each component
      was defined to accomplish important tasks. The result is a poly(ethylene glycol)
      (PEG)-protected redox-responsive dimeric paclitaxel (diPTX)-loaded cationic
      poly(d-glucose carbonate) micelle (diPTX@CPGC). These nanostructures showed
      tunable sizes and surface charges and displayed controlled PTX drug release
      profiles in the presence of reducing agents, such as glutathione (GSH) and
      dithiothreitol (DTT), thereby resulting in significant selectivity for killing
      cancer cells over healthy cells. Compared to free PTX and diPTX, diPTX@CPGC
      exhibited improved tumor penetration and significant inhibition of tumor cell
      growth toward osteosarcoma (OS) lung metastases with minimal side effects both in
      vitro and in vivo, indicating the promise of diPTX@CPGC as optimized anticancer
      therapeutic agents for treatment of OS lung metastases.

PMID- 29350524
TI  - Development of a Multiplexed Microsphere PCR for Culture-Free Detection and Gram
      Typing of Bacteria in Human Blood Samples.
AB  - Bloodstream infection is a significant clinical problem, particularly in
      vulnerable patient groups such as those undergoing chemotherapy and bone marrow
      transplantation. Clinical diagnostics for suspected bloodstream infection remain
      centered around blood culture (highly variable timing, in the order of hours to
      days to become positive), and empiric use of broad-spectrum antibiotics is
      therefore employed for patients presenting with febrile neutropenia. Gram-typing
      provides the first opportunity to target therapy (e.g., combinations containing
      vancomycin or teicoplanin for Gram-positives; piperacillin-tazobactam or a
      carbapenem for Gram-negatives); however, current approaches require blood
      culture. In this study, we describe a multiplexed microsphere-PCR assay with flow
      cytometry readout, which can distinguish Gram-positive from Gram-negative
      bacterial DNA in a 3.5 h time period. The combination of a simple assay design
      (amplicon-dependent release of Gram-type specific Cy3-labeled oligonucleotides)
      and the Luminex-based readout (for quantifying each specific Cy3-labeled
      sequence) opens opportunities for further multiplexing. We demonstrate the
      feasibility of detecting common Gram-positive and Gram-negative organisms after
      spiking whole bacteria into healthy human blood prior to DNA extraction. Further
      development of DNA extraction methods is required to reach detection limits
      comparable to blood culture.

PMID- 29350525
TI  - Microporous Luminescent Metal-Organic Framework for a Sensitive and Selective
      Fluorescence Sensing of Toxic Mycotoxin in Moldy Sugarcane.
AB  - Food contamination by toxic mycotoxins not only causes a considerable loss in
      economy, but importantly poses a huge threat to human health through accidental
      ingestion. Hence, it is an ongoing and imperative need to develop a convenient,
      cost-effective method for the detection of the mycotoxin-infected agricultural
      commodities. To this end, we herein fabricated a novel metal-organic framework
      derived composite material that displays a strong solid-state emission in the
      visible region, by attaching a frequently used fluorescent label, fluorescein
      isothiocyanate (FITC), via guest adsorption. Significantly, owing to the inherent
      pH-responsive conformational changes of FITC, the resulting composite material
      provides, to the best of our knowledge, the first example of the sensitive and
      selective fluorescence sensing toward 3-nitropropionic acid, which, as a major
      naturally occurring mycotoxin in moldy sugarcane, has been closely linked to
      poisoning episodes in human beings and animals.

PMID- 29350523
TI  - Amphiphilic pi-Allyliridium C,O-Benzoates Enable Regio- and Enantioselective
      Amination of Branched Allylic Acetates Bearing Linear Alkyl Groups.
AB  - The first examples of amphiphilic reactivity in the context of enantioselective
      catalysis are described. Commercially available pi-allyliridium C,O-benzoates,
      which are stable to air, water and SiO2 chromatography, and are well-known to
      catalyze allyl acetate-mediated carbonyl allylation, are now shown to catalyze
      highly chemo-, regio- and enantioselective substitutions of branched allylic
      acetates bearing linear alkyl groups with primary amines.

PMID- 29350526
TI  - Folding Graphene Film Yields High Areal Energy Storage in Lithium-Ion Batteries.
AB  - We show that a high energy density can be achieved in a practical manner with
      freestanding electrodes without using conductive carbon, binders, and current
      collectors. We made and used a folded graphene composite electrode designed for a
      high areal capacity anode. The traditional thick graphene composite electrode,
      such as made by filtering graphene oxide to create a thin film and reducing it
      such as through chemical or thermal methods, has sluggish reaction kinetics.
      Instead, we have made and tested a thin composite film electrode that was folded
      several times using a water-assisted method; it provides a continuous electron
      transport path in the fold regions and introduces more channels between the
      folded layers, which significantly enhances the electron/ion transport kinetics.
      A fold electrode consisting of SnO2/graphene with high areal loading of 5 mg cm-2
      has a high areal capacity of 4.15 mAh cm-2, well above commercial graphite anodes
      (2.50-3.50 mAh cm-2), while the thickness is maintained as low as ~20 MUm. The
      fold electrode shows stable cycling over 500 cycles at 1.70 mA cm-2 and improved
      rate capability compared to thick electrodes with the same mass loading but
      without folds. A full cell of fold electrode coupled with LiCoO2 cathode was
      assembled and delivered an areal capacity of 2.84 mAh cm-2 after 300 cycles. This
      folding strategy can be extended to other electrode materials and rechargeable
      batteries.

PMID- 29350527
TI  - Shuttle Suppression by Polymer-Sealed Graphene-Coated Polypropylene Separator.
AB  - "Shuttle effect" of lithium polysulfides (LiPS) leads to a poor performance and a
      short cycle life of the Li-S battery, thus limiting their practical application.
      We demonstrate here that after coating polypropylene (PP) separator with a
      continuous monolayer graphene, the shuttle effect can be significantly suppressed
      by limiting the passage of long-chain LiPS. The graphene/PP separator can be
      further modified by sealing the big holes or pores on graphene with in situ
      polymerized nylon-66 via an interfacial polymerization reaction between diamine
      and adipoyl chloride supplied by the aqueous and oil phase, respectively, from
      each side of the membrane. With this engineered membrane, an initial specific
      capacity of 1128.4 mAh g-1 at 0.05C is achieved after test in a coin cell, higher
      than that of 983.2 mAh g-1 with pristine PP, along with increased Coulombic
      efficiency from 96.0 to 99.9% and enhanced cycling durability. Molecular dynamics
      simulations attest that the nanopores with appropriate size and structure are
      effective in acting as a "sieve" to selectively allow only Li+ ions to pass
      through but prevent LiPS from migrating to the anode, consequently alleviating
      the shuttle effect. Our method provides a facile solution toward the mitigated
      shuttle effect and eventually contributes to the high performance of Li-S
      battery.

PMID- 29350528
TI  - Proton and Carbon-13 Dynamic Nuclear Polarization of Methylated beta
      Cyclodextrins.
AB  - 1H and 13C dynamic nuclear polarizations have been studied in 13C-enriched beta
      cyclodextrins doped with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl free radical. 1H
      and 13C polarizations raised above 7.5 and 7%, respectively, and for both nuclear
      species, the transfer of polarization from the electron spins appears to be
      consistent with a thermal mixing scenario for a concentration of 9 13C nuclei per
      molecule. When the concentration is increased to 21 13C nuclei per molecule, a
      decrease in the spin-lattice relaxation and polarization buildup rates is
      observed. This reduction is associated with the bottleneck effect induced by the
      decrease in the number of electron spins per nucleus when both the nuclear spin
      lattice relaxation and the polarization occur through the electron non-Zeeman
      reservoir. 13C nuclear spin-lattice relaxation has been studied in the 1.8-340 K
      range, and the effects of internal molecular motions and of the free radicals on
      the relaxation are discussed. 13C hyperpolarization performances and room
      temperature spin-lattice relaxation times show that these are promising materials
      for future biomedical applications.

PMID- 29350529
TI  - Colorimetric DNAzyme Biosensor for Convenience Detection of Enterotoxin B
      Harboring Staphylococcus aureus from Food Samples.
AB  - In the present study, a colorimetric DNAzymes biosensor strategy was devised in
      combination with immunomagnetic separation for rapid and easy detection of
      enterotoxin B harboring Staphylococcus aureus from food and clinical samples. The
      method employs immunocapture of S. aureus and amplification of seb gene by
      DNAzyme complementary sequence integrated forward primer and with specific
      reverse primer. The DNAzyme sequence integrated dsDNA PCR products when treated
      with hemin and TMB (3,3',5,5'-tetramethylbenzidine) in the presence of H2O2
      produce colorimetric signal. A linear relationship of optical signal with the
      initial template of seb was obtained which could be monitored by visually or
      spectrophotrometrically for qualitative and quantitative detection. The limit of
      detection for the assay was approximately 102 CFU/mL of seb gene harboring
      target. This method is convenient compared to gel based and ELISA systems.
      Further, spiking studies and analysis on natural samples emphasized the
      robustness and applicability of developed method. Altogether, the established
      assay could be a reliable alternative, low-cost, viable detection tool for the
      routine investigation of seb from food and clinical sources.

PMID- 29350530
TI  - Structural Variation and Microrheological Properties of a Homogeneous
      Polysaccharide from Wheat Germ.
AB  - A novel polysaccharide (WGP) was purified from crude wheat germ polysaccharide by
      Sephacryl S-500HRgel filtration. The molecular weight of WGP was determined as
      4.89 * 106 Da and consisted of arabinose, xylose, glucose, and galactose.
      Methylation analysis and 1D/2D nuclear magnetic resonance was used to analyze the
      structural characterization of WGP. WGP was mainly a backbone composed of (1 ->
      4)-linked-beta-d-Xylp (19.01%) and (1 -> 3, 4)-linked-beta-d-Xylp (26.27%)
      residues, which was branched of (1 -> 5)-linked alpha-l-Araf (28.09%) and (1 ->
      3,6)-linked beta-d-Galp (12.11%) with beta-d-Glcp (14.52%) as terminal unit. The
      calculated values of Turbiscan stability indexes suggested that WGP (0.1-0.5
      mg/mL) is a stable system. Microrheology results showed that WGP can form gel
      behavior when the concentration of WGP ranges from 0.1 to 3 mg/mL. Results of in
      vitro assays showed that WGP could cause the proliferation of RAW264.7
      macrophages, upregulating the release of TNF-alpha and IL-8 in the lymphocytes.

PMID- 29350531
TI  - On the Electronic Structure of Cu Chlorophyllin and Its Breakdown Products: A
      Carbon K-Edge X-ray Absorption Spectroscopy Study.
AB  - Using near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, the carbon
      backbone of sodium copper chlorophyllin (SCC), a widely used chlorophyll
      derivative, and its breakdown products are analyzed to elucidate their electronic
      structure and physicochemical properties. Using various sample preparation
      methods and complementary spectroscopic methods (including UV/Vis, X-ray
      photoelectron spectroscopy), a comprehensive insight into the SCC breakdown
      process is presented. The experimental results are supported by density
      functional theory calculations, allowing a detailed assignment of characteristic
      NEXAFS features to specific C bonds. SCC can be seen as a model system for the
      large group of porphyrins; thus, this work provides a novel and detailed
      description of the electronic structure of the carbon backbone of those molecules
      and their breakdown products. The achieved results also promise prospective
      optical pump/X-ray probe investigations of dynamic processes in chlorophyll
      containing photosynthetic complexes to be analyzed more precisely.

PMID- 29350532
TI  - Design of Exceptionally Strong Organic Superbases Based on Aromatic Pnictogen
      Oxides: Computational DFT Analysis of the Oxygen Basicity in the Gas Phase and
      Acetonitrile Solution.
AB  - DFT B3LYP calculations convincingly showed that aromatic pnictogen oxides offer
      scaffolds suitable for tailoring powerful organic superbases exhibiting
      exceptional oxygen basicity in both the gas phase and polar aprotic acetonitrile
      solution. With their protonation enthalpies and pKa values, they surpass the
      basicity of classical proton sponges and related nitrogen bases. The most potent
      system is provided with two arsenic oxide moieties on the phenanthrene framework
      assisted by the two phosphazeno groups in the para-position to both basic
      centers. With its proton affinity PA = 300.5 kcal mol-1, the latter system breaks
      the gas-phase hyperbasicity threshold of 300 kcal mol-1, while its pKa = 54.8
      promotes it as an unprecedented superbase in acetonitrile. The origin of such a
      dramatic basicity enhancement is traced to a fine interplay between (a) steric
      repulsions of the two negatively charged oxygens destabilizing a neutral base,
      (b) favorable intramolecular [O-H...O]- hydrogen bonding in conjugate acids, and
      (c) efficient cationic resonance upon protonation supported by the electron
      donating substituents. Given the growing interest in highly basic compounds
      together with related basic catalysts and metal complexing agents, we hope that
      the results presented here will open a new avenue of research in these fields and
      direct attention toward utilizing aromatic pnictogen oxides in designing improved
      organic materials.

PMID- 29350533
TI  - Development of Pickering Emulsions Stabilized by Gliadin/Proanthocyanidins Hybrid
      Particles (GPHPs) and the Fate of Lipid Oxidation and Digestion.
AB  - This work attempted to engineer emulsions' interface using the special affinity
      between proline-rich gliadin and proanthocyanidins (PA), to develop surfactant
      free antioxidant Pickering emulsions with digestive-resistant properties. This
      binding interaction between gliadin and PA benefited the interfacial adsorption
      of the particles to corn oil droplets. Pickering droplets as building units
      assembled into an interconnected three-dimensional network structure, giving the
      emulsions viscoelasticity and ultrastability. Oxidative markers in Pickering
      emulsions were periodically monitored under thermally accelerated storage. Lipid
      digestion and oxidation fates were characterized using in vitro gastrointestinal
      (GI) models. The interfacial membrane constructed by antioxidant particles served
      as a valid barrier against lipid oxidation and digestion, in a PA dose-dependent
      manner. Briefly, lipid oxidation under storage and simulated GI tract was
      retarded. Free fatty acid (FFA) fraction released decreased by 55% from 87.9%
      (bulk oil) to 39.5% (Pickering emulsion), implying engineering interfacial
      architecture potentially benefited to fight obesity. This study opens a facile
      strategy to tune lipid oxidation and digestion profiles through the cooperation
      of the Pickering principle and the interfacial delivery of antioxidants.

PMID- 29350534
TI  - Discovery of Tetrahydroisoquinoline-Containing CXCR4 Antagonists with Improved in
      Vitro ADMET Properties.
AB  - CXCR4 is a seven-transmembrane receptor expressed by hematopoietic stem cells and
      progeny, as well as by >=48 different cancers types. CXCL12, the only chemokine
      ligand of CXCR4, is secreted within the tumor microenvironment, providing
      sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic
      elimination by (1) stimulating prosurvival signaling and (2) recruiting CXCR4+
      immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract
      and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can
      potentially obstruct CXCR4-mediated prosurvival signaling, recondition the CXCR4+
      leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+
      cancer cell metastasis. Current small molecule CXCR4 antagonists suffer from poor
      oral bioavailability and off-target liabilities. Herein, we report a series of
      novel tetrahydroisoquinoline-containing CXCR4 antagonists designed to improve
      intestinal absorption and off-target profiles. Structure-activity relationships
      regarding CXCR4 potency, intestinal permeability, metabolic stability, and
      cytochrome P450 inhibition are presented.

PMID- 29350535
TI  - Contact Charge Electrophoresis: Fundamentals and Microfluidic Applications.
AB  - Contact charge electrophoresis (CCEP) uses steady electric fields to drive the
      oscillatory motion of conductive particles and droplets between two or more
      electrodes. In contrast to traditional forms of electrophoresis and
      dielectrophoresis, CCEP allows for rapid and sustained particle motions driven by
      low-power dc voltages. These attributes make CCEP a promising mechanism for
      powering active components for mobile microfluidic technologies. This Feature
      Article describes our current understanding of CCEP as well as recent strategies
      to harness it for applications in microfluidics and beyond.

PMID- 29350536
TI  - Diagnostic accuracy of functional, imaging and biochemical tests for patients
      presenting with chest pain to the emergency department: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Non-invasive ischaemia tests and biomarkers are widely adopted to
      rule out acute coronary syndrome in the emergency department. Their diagnostic
      accuracy has yet to be precisely defined. METHODS: Medline, Cochrane Library
      CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1
      September 2016, end date 1 December 2016). Prospective studies (observational or
      randomised controlled trial) comparing functional/imaging or biochemical tests
      for patients presenting with chest pain to the emergency department were
      included. RESULTS: Overall, 77 studies were included, for a total of 49,541
      patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T
      protocols did not show significant differences in their ability to detect acute
      coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95%
      confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83
      (0.70-0.92), respectively. The addition of copeptin to troponin increased
      sensitivity and reduced specificity, without improving diagnostic accuracy. The
      diagnostic value of non-invasive tests for patients without troponin increase was
      tested. Coronary computed tomography showed the highest level of diagnostic
      accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along
      with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and
      specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary
      computed tomography but non-inferior to myocardial perfusion scintigraphy, while
      exercise testing showed the lower level of diagnostic accuracy. CONCLUSIONS: Fast
      and six-hour highly sensitive troponin T protocols provide an overall similar
      level of diagnostic accuracy to detect acute coronary syndrome. Among the non
      invasive ischaemia tests for patients without troponin increase, coronary
      computed tomography and myocardial perfusion scintigraphy showed the highest
      sensitivity and specificity.

PMID- 29350537
TI  - Cartilage Morphological and Histological Findings After Reconstruction of the
      Glenoid With an Iliac Crest Bone Graft.
AB  - BACKGROUND: The J-bone graft is presumably representative of iliac crest bone
      grafts in general and allows anatomic glenoid reconstruction in cases of bone
      defects due to recurrent traumatic anterior shoulder dislocations. As a side
      effect, these grafts have been observed to be covered by some soft, cartilage
      like tissue when arthroscopy has been indicated after such procedures. PURPOSE:
      To evaluate the soft tissue covering of J-bone grafts by use of magnetic
      resonance imaging (MRI) and histological analysis. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: Patients underwent MRI at 1 year after the J-bone
      graft procedures. Radiological data were digitally processed and evaluated by
      segmentation of axial images. Independent from the MRI analysis, 2 biopsy
      specimens of J-bone grafts were harvested for descriptive histological analysis.
      RESULTS: Segmentation of the images revealed that all grafts were covered by soft
      tissue. This layer had an average thickness of 0.87 mm compared with 1.96 mm at
      the adjacent native glenoid. Of the 2 biopsy specimens, one exhibited evident
      hyaline-like cartilage and the other presented patches of chondrocytes embedded
      in a glycosaminoglycan-rich extracellular matrix. CONCLUSION: J-bone grafts are
      covered by soft tissue that can differentiate into fibrous and potentially
      hyaline cartilage. This feature may prove beneficial for delaying the onset of
      dislocation arthropathy of the shoulder.

PMID- 29350538
TI  - Potential Second-Harmonic Ghost Bands in Fourier Transform Infrared (FT-IR)
      Difference Spectroscopy of Proteins.
AB  - Fourier transform infrared (FT-IR) difference absorption spectroscopy is a common
      method for studying the structural and dynamical aspects behind protein function.
      In particular, the 2800-1800 cm-1 spectral range has been used to obtain
      information about internal (deuterated) water molecules, as well as site-specific
      details about cysteine residues and chemically modified and artificial amino
      acids. Here, we report on the presence of ghost bands in cryogenic light-induced
      FT-IR difference spectra of the protein bacteriorhodopsin. The presence of these
      ghost bands can be particularly problematic in the 2800-1900 cm-1 region, showing
      intensities similar to O-D vibrations from water molecules. We demonstrate that
      they arise from second harmonics from genuine chromophore bands located in the
      1400-850 cm-1 region, generated by double-modulation artifacts caused from
      reflections of the IR beam at the sample and at the cryostat windows back to the
      interferometer (inter-reflections). The second-harmonic ghost bands can be
      physically removed by placing an optical filter of suitable cutoff in the beam
      path, but at the cost of losing part of the multiplexing advantage of FT-IR
      spectroscopy. We explored alternatives to the use of optical filters. Tilting the
      cryostat windows was effective in reducing the intensity of the second harmonic
      artifacts but tilting the sample windows was not, presumably by their close
      proximity to the focal point of the IR beam. We also introduce a simple numerical
      post-processing approach that can partially, but not fully, correct for second
      harmonic ghost bands in FT-IR difference spectra.

PMID- 29350540
TI  - Analytical Methods to Distinguish the Positive and Negative Spectra of Mineral
      and Environmental Elements Using Deep Ablation Laser-Induced Breakdown
      Spectroscopy (LIBS).
AB  - Environments affect mineral surfaces, and the surface contamination or alteration
      can provide potential information to understanding their regional environments.
      However, when investigating mineral surfaces, mineral and environmental elements
      appear mixed in data. This makes it difficult to determine their atomic
      compositions independently. In this research, we developed four analytical
      methods to distinguish mineral and environmental elements into positive and
      negative spectra based on depth profiling data using laser-induced breakdown
      spectroscopy (LIBS). The principle of the methods is to utilize how intensity
      varied with depth for creating a new spectrum. The methods were applied to five
      mineral samples exposed to four environmental conditions including seawater,
      crude oil, sulfuric acid, and air as control. The proposed methods are then
      validated by applying the resultant spectra to principal component analysis and
      data were classified by the environmental conditions and atomic compositions of
      mineral. By applying the methods, the atomic information of minerals and
      environmental conditions were successfully inferred in the resultant spectrum.

PMID- 29350539
TI  - Effectiveness and safety of CT-guided percutaneous radiofrequency ablation of
      adrenal metastases.
AB  - OBJECTIVE: The imaging-guided percutaneous radiofrequency (RF) ablation of
      adrenal metastases is a relatively new treatment procedure, compared to the more
      widespread application of the technique for the treatment of liver and renal
      cancers. The present study aims to evaluate the safety and efficacy of the CT
      guided percutaneous RF ablation of adrenal metastases in a cohort of patients.
      METHODS: 33 patients with 38 adrenal metastases who received percutaneous CT
      guided RF ablation between 2012 to 2015 were retrospectively reviewed. The
      average diameter of the treated adrenal metastases was 3.0 +/- 1.6 cm. The
      treatment outcomes, including presence of residual tumours, technical success
      rate, recurrence rate, and complications, were evaluated. Patients were followed
      up for every 3 months to monitor the progression of the disease. RESULTS:
      Postoperative CT images showed the lack of tumour enhancement in 30 tumours
      (30/38 tumours, technical success rate = 78.9%), and residual disease was found
      in 7 tumours (7/37 tumours, 18.9%). The rate of residual disease was
      significantly lower in the group with tumour size <3 cm than the group with
      tumour size >=3 cm (p = 0.025). The severe complication rate was 4.3%, and the
      mild complication rate was 48%, with intraoperative hypertensive crisis as the
      most frequently observed complication (27.3%). The follow-up data showed that
      76.3% of patients had recurrence-free survival in 27.4 months. CONCLUSION: The
      current study demonstrated that radiofrequency ablation is a relatively safe and
      effective treatment for controlling adrenal metastases, especially for patients
      with tumour size <3 cm. Advances in knowledge: Surgical resection of the adrenal
      metastases was advocated as one of the treatment options for patients. The
      present study showed that radiofrequency ablation is a relatively safe and
      effective treatment for controlling adrenal metastases.

PMID- 29350541
TI  - Using Cell Phone Technology to Investigate a Deliberate Bacillus anthracis
      Release Scenario.
AB  - Unusual biological events and outbreaks require rapid epidemiologic investigation
      and contact tracing procedures, allowing optimal handling of resources.
      Currently, these are resource intensive, time consuming, and extremely complex,
      requiring large teams of trained and prepared personnel. The goal of this study
      was to determine whether a technological alternative to the classic systems,
      based on the use of mobile phones and a unique algorithm, could perform a
      complete epidemiologic investigation in a setting of a bioterrorism scenario. The
      system was tested with 32 volunteers during a bioterrorism simulation drill, with
      quantitative assessment of key outcome measures: perform a complete analysis of
      the scenario, determine the fundamental biological attributes of the scenario,
      distinguish between related and unrelated cases, and identify possible exposed
      people among a known group of participants. The system fully achieved the
      objectives in just under 5 hours from the beginning of the simulation with only 3
      false-positive "exposed" participants, while identifying all 11 true-positive
      "exposed" participants (overall accuracy of 85%). We find the system advantageous
      over currently used tools in a way that could be integrated in conjunction with
      current outbreak epidemiologic investigation tools and syndromic surveillance
      efforts to shorten the response time of national authorities in handling adverse
      biological events.

PMID- 29350542
TI  - Preliminary investigation of social interactions and feeding behavior in captive
      group-housed Tasmanian devils (Sarcophilus Harrisii).
AB  - As the number of Tasmanian devils (Sarcophilus harrisii) in captivity increases,
      an understanding of captive social dynamics and behavior is becoming increasingly
      important. In the wild, devils are solitary, although sometimes, they congregate
      to feed on a large carcass. However, it is common to house devils in groups as a
      form of social enrichment. This study investigated how behavior at feeding time
      of captive Tasmanian devils varied in groups of different sizes. Observations
      were made of individually housed devils and devils in groups of two, three, five,
      and six, when presented with a carcass on which to feed. Total feeding duration
      ranged from 6.5 to 47.4 minutes per observation period (70 minutes). There was no
      significant interaction between feeding duration and group size during the
      experiment. Feeding duration varied daily and depended on carcass size. Social
      housing of Tasmanian devils enabled them to display dyadic and agonistic
      behaviors during feeding. Observing behaviors and learning from the outcomes of
      these interactions can improve husbandry techniques. Creating a captive
      environment that encourages natural behaviors may enhance survival in the wild
      following translocation.

PMID- 29350543
TI  - A Publicly Available Landscape Analysis Tool for Biodefense Policy.

PMID- 29350544
TI  - Erratum.

PMID- 29350545
TI  - Sensitive Multiplex Real-time RT-qPCR Assay for the Detection of Filoviruses.
AB  - Filoviruses are important etiological agents of emergent diseases with high
      mortality rates. Traditionally, filovirus fever diseases have primarily been a
      burden of African countries; however, global interconnectedness has increased the
      probability of the worldwide spread of filoviruses. Therefore, national
      healthcare organizations need tools for managing filovirus risk, including
      diagnostic kits based on real-time reverse transcription PCR (RT-qPCR), as this
      is the most suitable method for diagnosing filovirus fever diseases. Here we
      describe a real-time RT-qPCR assay for filovirus detection. This assay is a
      further development of our previously reported EBOV (Zaire)-Fl kit. Two sets
      (FiloA-Fl and FiloB-Fl) of real-time RT-qPCR assays for the detection of
      filoviruses were developed and evaluated using armored RNA phage particles (ARs)
      as positive controls. The limit of detection of the assay was 5x102 copies/ml of
      the AR-positive control for the FiloA-Fl set and 5x103 copies/ml of the AR
      positive control for the FiloB-Fl set. Our assay provides a rapid and sensitive
      tool for detecting filoviruses. The high specificity and sensitivity of the assay
      make it useful for clinical and epidemiologic investigations in the field of
      filovirus fever diseases and their etiological agents.

PMID- 29350546
TI  - 'We're like a gang, we stick together': experiences of ventricular assist device
      communities.
AB  - BACKGROUND: Ventricular assist devices (VADs) are a relatively new development in
      the management of advanced heart failure. In the UK, VAD recipients comprise a
      unique group of less than 200 patients. This is the first paper to explore the
      experience of VAD communities, the extent to which communities are developed
      around the device, and how these influence the experience of living with the VAD.
      METHODS: Qualitative interviews were conducted with 20 VAD recipients (implanted
      as a bridge to transplantation), 11 interviews also included the VAD recipients'
      partners. Interpretive phenomenology was employed as the theoretical basis
      guiding the analysis of the interviews. RESULTS: Four key themes emerged from the
      data: the existence of VAD communities; experiential knowledge and understanding;
      social comparisons; and the impacts of deaths within the VAD community. Many of
      the interviewees valued the VAD communities and the relationships they had formed
      with fellow recipients. The beneficial impacts of the VAD communities included
      offering recently implanted patients a realistic view of what to expect from life
      with a VAD; this could aid them in accepting and adapting to the changes imparted
      by the device. However, negative impacts of the VAD communities were also
      reported, in particular following deaths within the group, which were a source of
      distress for many of the interviewees. CONCLUSIONS: In general, the VAD
      communities appeared to be a beneficial source of support for the majority of
      interviewees. Consideration should be given to how these communities could be
      supported by clinicians.

PMID- 29350547
TI  - Regulation of Autophagy by Hepatitis C Virus for Its Replication.
AB  - Macroautophagy, hereafter autophagy, is a catabolic process that is important for
      maintaining cellular homeostasis. It can also be used by cells to remove
      intracellular microbial pathogens. However, the studies on hepatitis C virus
      (HCV) in recent years indicated that this virus could regulate this cellular
      pathway and use it to enhance its replication. HCV could temporally control the
      autophagic flux and use the autophagic membranes for the assembly of its RNA
      replication complex. In this report, we will discuss the biogenesis of
      autophagosomes induced by HCV and how HCV uses this autophagic pathway for its
      RNA replication.

PMID- 29350548
TI  - Use of helical tomotherapy in locally advanced and/or metastatic breast cancer
      for locoregional treatment.
AB  - OBJECTIVE: Helical tomotherapy (HT) is a new promising tool whose use remains to
      be studied. This work assesses its impact for local irradiation in terms of side
      effects, as well as tumour control in locally advanced (LABC) and metastatic
      breast cancer (MBC). METHODS: We retrospectively reviewed data of 66 patients
      with LABC and MBC. Patients received standard fractionated radiotherapy by HT,
      with or without concurrent systemic treatment. RESULTS: The median age was 60
      years (28-77). The median follow-up of the population was 35.9 months (10.6
      95.8). For 91% of patients, HT was concomitant with systemic treatments. Three
      patients experienced grade 3 skin toxicity and all had concurrent 5FU
      vinorelbine. One patient who was receiving concurrent treatment with trastuzumab
      pertuzumab had a decreased left ventricular ejection fraction by 14%. No late
      cardiac or lung toxicity was observed. A clinical benefit was observed in 75% of
      cases. At 2 months after HT, we observed tumour regression in 7/8 patients, as
      following: 1 complete, 4 partial responses, and 2 stable disease. The median
      survival for MBC group was 64.4 months (42.6-65.8) and 21.1 (6.1-36.1) months for
      LABC. CONCLUSION: This study suggests that the use of HT is well tolerated and
      feasible with a multimodal strategy that includes concurrent systemic treatments
      for patients with LABC and MBC. Advances in knowledge: The survival of LABC and
      MBC increases and new safe tools are needed to determine optimal strategies of
      treatment. To our knowledge, this is the first paper describing the use of HT for
      this population.

PMID- 29350549
TI  - Abiraterone acetate and its use in the treatment of metastatic prostate cancer: a
      review.
AB  - Abiraterone acetate, which targets enzymatic complexes playing a central role in
      steroidogenesis, demonstrated to increase survival significantly in both chemo
      naive and docetaxel pretreated, becoming one of the drugs of choice for
      metastatic castration-resistant prostate cancer. More recently, this agent in
      combination to androgen deprivation therapy demonstrated to be efficacious also
      in metastatic castration-sensitive prostate cancer. The present review is aimed
      to outline the clinical development of abiraterone acetate, the pivotal trials
      which led to its approval for the clinical practice, new evidence about its
      efficacy in metastatic castration-sensitive prostate cancer, its place in the
      therapeutic landscape of prostate cancer and future directions of development.

PMID- 29350550
TI  - Discrimination of Single Living Rat Pancreatic alpha, beta, delta, and Pancreatic
      Polypeptide (PP) Cells Using Raman Spectroscopy.
AB  - Primary pancreatic alpha, beta, delta, and pancreatic polypeptide (PP) cells are
      reliable cell models for diabetes research. However, the separation and
      purification of these cells in living conditions remains an obstacle for
      researchers. The interaction of visible light with cellular molecules can produce
      Raman scattering, which can be analyzed to obtain cellular intrinsic molecular
      fingerprints. It has been speculated that primary pancreatic alpha, beta, delta,
      and PP cells can be identified and separated from each other according to their
      spectral differences. To test this hypothesis, Raman spectra detection was
      performed on rat islet cells. Single islet cells identified by Raman scattering
      under living conditions were verified using immunohistochemistry. Thus, Raman
      data were acquired from a pure line of islet cells as a training sample and then
      used to establish the discriminant function. Then, using the principal component
      analysis-linear discriminate analysis (PCA-LDA) method, the four types of islet
      cells could be identified and discriminated by Raman spectroscopy. This study
      provides a label-free and noninvasive method for discriminating islet cell types
      in a randomly distributed mixed islet cell population via their physical
      properties rather than by using antibodies or fluorescence labeling.

PMID- 29350551
TI  - Hip and Knee Kinematics and Kinetics During Landing Tasks After Anterior Cruciate
      Ligament Reconstruction: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE:   To evaluate the current evidence concerning kinematic and kinetic
      strategies adopted during dynamic landing tasks by patients with anterior
      cruciate ligament reconstruction (ACLR). DATA SOURCES:   PubMed, Web of Science.
      STUDY SELECTION:   Original research articles that evaluated kinematics or
      kinetics (or both) during a landing task in those with a history of ACLR were
      included. DATA EXTRACTION:   Methodologic quality was assessed using the modified
      Downs and Black checklist. Means and standard deviations for knee or hip (or
      both) kinematics and kinetics were used to calculate Cohen d effect sizes and
      corresponding 95% confidence intervals between the injured limb of ACLR
      participants and contralateral or healthy matched limbs. Data were further
      stratified by landing tasks, either double- or single-limb landing. A random
      effects-model meta-analysis was used to calculate pooled effect sizes and 95%
      confidence intervals. DATA SYNTHESIS:   The involved limbs of ACLR patients
      demonstrated clinically and significantly lower knee-extension moments during
      double-legged landing compared with healthy contralateral limbs and healthy
      control limbs (Cohen d range = -0.81 to -1.23) and decreased vertical ground
      reaction forces when compared with healthy controls, regardless of task (Cohen d
      range = -0.39 to -1.75). CONCLUSIONS:   During single- and double-legged landing
      tasks, individuals with ACLR demonstrated meaningful reductions in injured-limb
      knee-extension moments and vertical ground reaction forces. These findings
      indicate potential unloading of the injured limb after ACLR, which may have
      significant implications for secondary ACL injury and long-term joint health.

PMID- 29350552
TI  - Role Strain, Part 2: Perceptions Among Athletic Trainers Employed in the
      Professional Practice Setting.
AB  - CONTEXT:   Athletic trainers (ATs) employed in the professional sport setting
      (ATPSSs) demonstrate moderate to high degrees of role strain. The experiences and
      perceptions of these ATs provide insight regarding the sources of role strain as
      well as ways to reduce it. OBJECTIVE:   To investigate the perceptions of ATPSSs
      regarding role strain. DESIGN:   Qualitative study. PATIENTS OR OTHER
      PARTICIPANTS:   From a purposeful sampling of 389 ATs employed in the 5 major
      sport leagues (Major League Baseball, Major League Soccer, National Basketball
      Association, National Football League, and National Hockey League), we identified
      34 participants willing to participate in phone interviews. Data Collection and
      Procedures:  Semistructured phone interviews. Inductive data analysis was based
      on a grounded theory approach. Credibility was addressed with member checks and a
      peer debriefing. RESULTS:   Three first-order emergent themes materialized from
      the data: (1) sources of role strain, (2) consequences of role strain, and (3)
      strategies to alleviate role strain in ATPSSs. Participants described the
      antecedents of role strain as emerging from the competing expectations of the
      professional athlete, the organization, and the sport league. Consequences of
      role strain included effects on direct patient care and work-life imbalance.
      Improving organizational factors such as inadequate staffing and poor
      communication within the organization were strategies described by participants
      for decreasing role strain in the professional sports setting. CONCLUSIONS:   Our
      participants discussed experiencing role strain, which was facilitated by trying
      to meet the competing demands placed on them with limited time and often with an
      inadequate support staff. Participant role strain affected health care and
      contributed to work-life imbalance. Participants described changing the
      organizational factors that contributed to role strain as a strategy to alleviate
      the perceived stress.

PMID- 29350553
TI  - Role Strain, Part 1: Experiences of Athletic Trainers Employed in the
      Professional Sports Setting.
AB  - CONTEXT:   The demands and expectations of athletic trainers employed in
      professional sports settings (ATPSSs) have increased over the years. Meeting
      these demands and expectations may predispose the athletic trainer to workplace
      stress and ultimately role strain. OBJECTIVE:   To investigate the concept of
      role strain among ATPSSs. DESIGN:   Sequential, explanatory mixed-methods study
      consisting of 2 phases: (1) population role-strain survey and (2) personal
      interviews. PATIENTS OR OTHER PARTICIPANTS:   From a purposeful sampling of 389
      athletic trainers employed in the 5 major sports leagues (Major League Baseball,
      Major League Soccer, National Basketball Association, National Football League,
      and National Hockey League), 152 individuals provided usable data (39% response
      rate). MAIN OUTCOME MEASURE(S):   A previously validated and reliable role-strain
      survey using a 5-point Likert scale (1 = never, 5 = nearly all the time) was
      administered. Measures of central tendency were used to identify the presence and
      degree of role strain; inferential statistics were calculated using analysis of
      variance to determine group differences in overall role strain and its
      subcomponents. RESULTS:   More than half of the participants (53.9%) experienced
      a moderate to high degree of role strain. Interrole conflict (2.99 +/- 0.77) and
      role overload (2.91 +/- 0.75) represented the most prominent components of role
      strain. Differences existed by sport leagues and employment. CONCLUSIONS:   Role
      strain existed at moderate to high levels (mean Role Strain Score > 2.70) among
      ATPSSs. Interrole conflict and role overload contributed the most to overall role
      strain. The ATPSSs experienced role strain to a higher degree than reported in
      other settings.

PMID- 29350554
TI  - Quadriceps Neuromuscular Function and Jump-Landing Sagittal-Plane Knee
      Biomechanics After Anterior Cruciate Ligament Reconstruction.
AB  - CONTEXT:   Aberrant biomechanics may affect force attenuation at the knee during
      dynamic activities, potentially increasing the risk of sustaining a knee injury
      or hastening the development of osteoarthritis after anterior cruciate ligament
      reconstruction (ACLR). Impaired quadriceps neuromuscular function has been
      hypothesized to influence the development of aberrant biomechanics. OBJECTIVE:  
      To determine the association between quadriceps neuromuscular function (strength,
      voluntary activation, and spinal-reflex and corticomotor excitability) and
      sagittal-plane knee biomechanics during jump landings in individuals with ACLR.
      DESIGN:   Cross-sectional study. SETTING:   Research laboratory. PATIENTS OR
      OTHER PARTICIPANTS:   Twenty-eight individuals with unilateral ACLR (7 men, 21
      women; age = 22.4 +/- 3.7 years, height = 1.69 +/- 0.10 m, mass = 69.4 +/- 10.1
      kg, time postsurgery = 52 +/- 42 months). MAIN OUTCOME MEASURE(S):   We
      quantified quadriceps spinal-reflex excitability via the Hoffmann reflex
      normalized to maximal muscle response (H : M ratio), corticomotor excitability
      via active motor threshold, strength as knee-extension maximal voluntary
      isometric contraction (MVIC), and voluntary activation using the central
      activation ratio (CAR). In a separate session, sagittal-plane kinetics (peak
      vertical ground reaction force [vGRF] and peak internal knee-extension moment)
      and kinematics (knee-flexion angle at initial contact, peak knee-flexion angle,
      and knee-flexion excursion) were collected during the loading phase of a jump
      landing task. Separate bivariate associations were performed between the
      neuromuscular and biomechanical variables. RESULTS:   In the ACLR limb, greater
      MVIC was associated with greater peak knee-flexion angle ( r = 0.38, P = .045)
      and less peak vGRF ( r = -0.41, P = .03). Greater CAR was associated with greater
      peak internal knee-extension moment (rho = -0.38, P = .045), and greater H : M
      ratios were associated with greater peak vGRF ( r = 0.45, P = .02). CONCLUSIONS: 
      Greater quadriceps MVIC and CAR may provide better energy attenuation during a
      jump-landing task. Individuals with greater peak vGRF in the ACLR limb possibly
      require greater spinal-reflex excitability to attenuate greater loading during
      dynamic movements.

PMID- 29350555
TI  - Outcomes of the Latarjet Procedure Compared With Bankart Repair for Recurrent
      Traumatic Anterior Shoulder Instability.
AB  - : Reference/Citation:  An VV, Sivakumar BS, Phan K, Trantalis J. A systematic
      review and meta-analysis of clinical and patient-reported outcomes following two
      procedures for recurrent traumatic anterior instability of the shoulder: Latarjet
      procedure vs. Bankart repair. J Shoulder Elbow Surg. 2016;25(5):853-863. CLINICAL
      QUESTION:   Are clinical and patient-reported outcomes different between the
      Latarjet and Bankart repair stabilization procedures when performed for recurrent
      traumatic anterior shoulder instability? DATA SOURCES:   Ovid MEDLINE, PubMed,
      Cochrane databases, American College of Physicians Journal Club, and Database of
      Abstracts of Review of Effectiveness were searched up to June 2015. The search
      terms used were Bankart AND Latarjet OR Bristow. STUDY SELECTION:   Criteria used
      to include studies that (1) were written in English; (2) compared the outcomes of
      any Latarjet procedure (Bristow-Latarjet, coracoid transfer, or modified Bristow)
      with Bankart repair (anatomic); (3) reported a minimum of 1 outcome of
      recurrence, redislocation, revision, or patient-reported outcome measure; and (4)
      reported original data. DATA EXTRACTION:   Data presented in any format (text,
      table, figure) were extracted from all included studies. The quality of each
      study was assessed using the Strengthening the Reporting of Observational Studies
      in Epidemiology (STROBE) checklist. Summary statistics were reported as relative
      risks and weighted mean differences. Fixed-effects (the assumed treatment effect
      was the same across studies) and random-effects (variations in treatment effect
      were assumed among studies) models were tested. Heterogeneity between trials was
      assessed using the chi2 statistic, and the amount (percentage) of variation
      across studies due to heterogeneity was calculated using the I 2 statistic.
      Forest plots were used to present pooled results. MAIN RESULTS:   After the
      initial search, 245 articles were identified. After we applied the inclusion
      criteria, a total of 8 studies reporting on 795 patients (Latarjet = 379, Bankart
      = 416) were included in this review. Using the National Health and Medical
      Research Council's level of evidence, the authors scored 7 of the studies at
      level III and 1 study at level II. All Latarjet procedures were performed using
      an open technique, whereas the Bankart procedure was performed open in 6 studies
      and arthroscopically in 2 studies. The demographics of the patients (age,
      proportion of males to females, proportion with surgery on the dominant side, and
      proportion of revisions) were similar between the 2 surgical procedures. Four
      groups reported that patients who underwent the Latarjet procedure had fewer
      recurrences than patients in the Bankart repair group (11.6% versus 21.1%,
      respectively), irrespective of whether the Bankart was performed open or
      arthroscopically. Similarly, 4 groups observed that the Latarjet procedure
      resulted in fewer postsurgical redislocations (5.0%) than the Bankart (9.5%)
      procedure, irrespective of whether the repair was open or arthroscopic. The
      authors of 7 studies noted no differences between the 2 procedures in revision
      rates (Latarjet: 3.4%, Bankart: 4.5%), and 8 studies demonstrated no differences
      in complications requiring reoperation (Latarjet: 5.0%, Bankart: 3.1%).
      Investigators in 7 studies used the Rowe score to measure patient-reported
      satisfaction and function; patients who underwent the Latarjet procedure reported
      better Rowe scores postsurgically than patients who underwent the Bankart repair
      (scores: 79.0 and 85.4, respectively). Researchers in 4 studies reported a loss
      of external-rotation range of motion, which was less in the Latarjet (11.5
      degrees ) compared with the Bankart (20.9 degrees ) procedure. Of the 5 groups
      that reported return to function, a trend suggested that a greater proportion of
      patients who underwent the Latarjet procedure returned to work, sport, and
      throwing activities compared with those who underwent the Bankart repair.
      CONCLUSIONS:   The Latarjet procedure produced fewer recurrences, better patient
      reported outcomes, and less restricted external-rotation motion than the Bankart
      repair.

PMID- 29350556
TI  - Rehabilitation of a Young Athlete With Extension-Based Low Back Pain Addressing
      Motor-Control Impairments and Central Sensitization.
AB  - OBJECTIVE:   To describe the conservative management of a young athlete with
      extension-based (EB) low back pain (LBP). BACKGROUND:   We present the case of a
      15-year-old female high school gymnast with a 4-year history of EB LBP. Magnetic
      resonance imaging revealed a healed spondylolysis and significant atrophy with
      fatty infiltrate of the lumbar multifidi muscles (LMM). She had several courses
      of outpatient orthopaedic rehabilitation that focused on core muscle
      strengthening (improving activation and strength of the LMM and transversus
      abdominus muscle in a neutral pelvic position) without long-lasting improvement.
      She was unable to tolerate higher levels of training or compete. DIFFERENTIAL
      DIAGNOSIS:   The LMM are rich in muscle spindles and provide continuous feedback
      to the central nervous system about body position. Atrophy and fatty infiltrate
      of the LMM can compromise neuromuscular function and contribute to dysfunctional
      movement patterns that place a greater demand on lumbar spine structures. Ongoing
      motor-control impairments perpetuate nociceptive input, leading to central
      sensitization. TREATMENT:   The athlete had difficulty controlling trunk
      extension during sport-specific activities; she moved early and to a greater
      extent in the lumbar spine. The aim of the treatment was to teach the athlete how
      to control her tendency to overload her lumbar spine when bending backward, thus
      reducing nociceptive input from lumbar spine structures and desensitizing the
      nervous system. UNIQUENESS:   Treating EB LBP by addressing motor-control
      impairments and cognitive-affective factors as opposed to core strengthening.
      CONCLUSIONS:   Activity modification, bracing, and traditional core-strengthening
      exercises may not be the most appropriate treatment for athletes experiencing EB
      LBP. Addressing cognitive-affective factors in addition to correcting maladaptive
      motor behavior and moving in a pain-free range reduces nociceptive input,
      desensitizes the nervous system, and allows athletes to gain control over their
      pain.

PMID- 29350557
TI  - Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) include alpha-linolenic acid (ALA;
      18:3 omega-3), stearidonic acid (SDA; 18:4 omega-3), eicosapentaenoic acid (EPA;
      20:5 omega-3), docosapentaenoic acid (DPA; 22:5 omega-3), and docosahexaenoic
      acid (DHA; 22:6 omega-3). In the past few decades, many epidemiological studies
      have been conducted on the myriad health benefits of omega-3 PUFAs. In this
      review, we summarized the structural features, properties, dietary sources,
      metabolism, and bioavailability of omega-3 PUFAs and their effects on
      cardiovascular disease, diabetes, cancer, Alzheimer's disease, dementia,
      depression, visual and neurological development, and maternal and child health.
      Even though many health benefits of omega-3 PUFAs have been reported in the
      literature, there are also some controversies about their efficacy and certain
      benefits to human health.

PMID- 29350558
TI  - Synbiotics for Improved Human Health: Recent Developments, Challenges, and
      Opportunities.
AB  - Research on combining pro- and prebiotics as synbiotics to enhance human and
      animal health has accelerated in the past 10 years, including many clinical
      trials that have assessed a diverse range of synbiotic formulations. In this
      review, we summarize these studies as well as the commercial applications of
      synbiotics that are available. In particular, we critically assess the claimed
      health benefits of synbiotic applications and the ecological and therapeutic
      factors to consider when designing synbiotics and discuss the implications of
      these concepts for future research in this field.

PMID- 29350559
TI  - Visualizing 3D Food Microstructure Using Tomographic Methods: Advantages and
      Disadvantages.
AB  - X-ray micro-computed tomography (micro-CT) provides the unique ability to capture
      intact internal microstructure data without significant preparation of the
      sample. The fundamentals of micro-CT technology are briefly described along with
      a short introduction to basic image processing, quantitative analysis, and
      derivative computational modeling. The applications and limitations of micro-CT
      in industries such as meat, dairy, postharvest, and bread/confectionary are
      discussed to serve as a guideline to the plausibility of utilizing the technique
      for detecting features of interest. Component volume fractions, their respective
      size/shape distributions, and connectivity, for example, can be utilized for
      product development, manufacturing process tuning and/or troubleshooting. In
      addition to determining structure-function relations, micro-CT can be used for
      foreign material detection to further ensure product quality and safety. In most
      usage scenarios, micro-CT in its current form is perfectly adequate for
      determining microstructure in a wide variety of food products. However, in low
      contrast and low-stability samples, emphasis is placed on the shortcomings of the
      current systems to set realistic expectations for the intended users.

PMID- 29350560
TI  - Formation, Structure, and Functionality of Interfacial Layers in Food Emulsions.
AB  - Emulsions, i.e., the dispersion of liquid droplets in a nonmiscible liquid phase,
      are overwhelmingly present in food products. In such systems, both liquid phases
      (generally, oil and water) are separated by a narrow region, the oil-water
      interface. Despite the fact that this interface is very thin (in the nanometer
      range), it represents a large surface area and controls to a great extent the
      physicochemical stability of emulsions. This review provides an overview of the
      aspects that govern the composition, structure, and mechanical properties of
      interfaces in food emulsions, taking into account the complexity of such systems
      (presence of numerous surface-active molecules, influence of processing steps,
      and dynamic evolution due to chemical changes). We also review methods that have
      conventionally, or recently, been used to study liquid-liquid interfaces at
      various scales. Finally, we focus on the link between interfacial properties and
      the physical, chemical, and digestive stability of emulsions at different levels
      and point out trends to control stability via interfacial engineering.

PMID- 29350561
TI  - Recent Past, Present, and Future of the Food Microbiome.
AB  - Sequencing technologies have deeply changed our approach to the study of food
      microbial communities. This review describes recent exploitations of high
      throughput sequencing applications to improve our knowledge of food microbial
      consortia. In the past 10 years, target amplicon sequencing has become routinely
      used in many food microbiology laboratories, providing a detailed picture of food
      associated microbiota. Metagenomics and metatranscriptomics approaches are still
      underexploited in food microbial ecology, despite their potential to uncover the
      functionality of complex communities. In a near future, sequencing technologies
      will surely advance our understanding of how to effectively use the invaluable
      microbial resources to improve food quality and safety.

PMID- 29350562
TI  - Enzymes in Lipid Modification.
AB  - This article reviews the application of enzymes in lipid modification. Lipases
      are the most established biocatalysts used for the synthesis of structured
      triacylglycerols, fats, and margarine and for the release of flavoring fatty
      acids for food applications. In addition, the various enzymes, such as P450
      monooxygenases, hydratases, lipoxygenases, and certain lyases, used for
      oxyfunctionalization and the phospholipases used for degumming are covered. Basic
      aspects of enzyme catalysis and the modern tools used for their discovery and
      improvement by protein engineering provide insight into how suitable biocatalysts
      can be identified and optimized for an application. In addition to isolated
      enzymes, whole-cell engineered microorganisms are also used for lipid
      modification. Thus, the polyunsaturated fatty acid EPA (eicosapentaenoic acid)
      can be produced in a yeast using sugar as a renewable resource.

PMID- 29350563
TI  - Dietary Advanced Glycosylation End-Products (dAGEs) and Melanoidins Formed
      through the Maillard Reaction: Physiological Consequences of their Intake.
AB  - The main purpose of this review is to clarify whether the consumption of food
      rich in melanoidins and dietary advanced glycosylation end-products (dAGEs) is
      harmful or beneficial for human health. There are conflicting results on their
      harmful effects in the literature, partly due to a methodological issue in how
      dAGEs are determined in food. Melanoidins have positive functions particularly
      within the gastrointestinal tract, whereas the intake of dAGEs has controversial
      physiological consequences. Most of the in vivo intervention trials were done
      comparing boiled versus roasted diet (low and high dAGE, respectively). However,
      these studies can be biased by different lipid oxidation and by different calorie
      density of foods in the two conditions. The attraction that humans have to cooked
      foods is linked to the benefits they have had during mankind's evolution. The
      goal for food technologists is to design low-energy-dense products that can
      satisfy humans' attraction to rewarding cooked foods.

PMID- 29350564
TI  - Role of MAdCAM-1-Expressing High Endothelial Venule-Like Vessels in Colitis
      Induced in Mice Lacking Sulfotransferases Catalyzing L-Selectin Ligand
      Biosynthesis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease histologically
      characterized by diffuse mononuclear cell infiltrates in colonic mucosa. These
      inflammatory cells are considered to be recruited via high endothelial venule
      (HEV)-like vessels displaying mucosal addressin cell adhesion molecule 1 (MAdCAM
      1), the ligand for alpha4beta7 integrin, and/or peripheral lymph node addressin
      (PNAd), an L-selectin ligand. 6- O-sulfation of N-acetylglucosamine in the
      carbohydrate moiety of PNAd is catalyzed exclusively by N-acetylglucosamine-6- O
      sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2. To determine the role of 6- O
      sulfation of N-acetylglucosamine on HEV-like vessels in UC, we used a chronic
      dextran sulfate sodium-induced colitis model using mice deficient in both
      GlcNAc6ST-1 and GlcNAc6ST-2. We found that more inflammatory cells, with
      expression of tumor necrosis factor alpha, were infiltrated in double knockout
      mouse colitis compared with that in wild-type mice. Moreover, the number of
      MAdCAM-1-positive vessels was increased in double knockout mouse colitis, and
      these vessels were bound by E-selectin*IgM chimeras that bind to unsulfated
      sialyl Lewis X (sLeX). These findings suggest that interactions between MAdCAM-1
      and alpha4beta7 integrin and/or unsulfated sLeX and L-selectin may become a
      dominant mechanism for inflammatory cell recruitment in the absence of 6-sulfo
      sLeX and contribute to more severe colitis phenotypes seen in double knockout
      mice.

PMID- 29350565
TI  - Safety and efficacy of denosumab in osteoporotic patients previously treated with
      other medications: a systematic review and meta-analysis.
AB  - INTRODUCTION: Denosumab is a monoclonal antibody that received approval by the
      FDA for the treatment of osteoporosis in 2010. Available higher level research
      evidence concerns the treatment of patients that have not received any anti
      osteoporotic medication in the past. Further investigation is warranted, since
      clinicians often face the challenge of administering the most efficacious drug in
      patients, pretreated with other medications. Areas covered: We conducted a
      systematic review and meta-analysis to evaluate the efficacy and safety of
      denosumab compared to other active anti-osteoporotic agents in patients formerly
      receiving other treatments. We searched MEDLINE, EMBASE, CENTRAL, the
      metaRegister of Controlled Trials (mRCT) and clinicaltrials.gov up to April 2017
      to identify eligible trials in patients with primary osteoporosis. Expert
      opinion: Our meta-analysis included 6 Randomised Controlled Trials encompassing
      2968 patients formerly treated with anti-osteoporotic medications. Quantitative
      data synthesis demonstrated superiority of denosumab in augmenting Bone Mineral
      Density in all skeletal sites studied compared to controls [treatment difference
      in total hip: 1.59% (95% CI 1.01, 2.17)], whereas the overall incidence of
      serious adverse events was not increased (OR 1.12, 95% CI 0.85 to 1.47, p =
      0.42). Future research geared towards the fracture incidence, quality of life and
      patient reported outcomes is warranted.

PMID- 29350566
TI  - ABP 501 for the treatment of rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease, which has a
      negative impact on the ability to perform activities daily. Tumour necrosis
      factor alpha (TNF) is a cytokine with diverse cellular effects, and a key
      regulator of the inflammatory response. ABP 501 is a biosimilar to adalimumab, a
      TNF inhibitor. Areas covered: In this review, we examined ABP 501, as a
      biosimilar candidate to adalimumab in the treatment of RA focusing on the
      available data. Current data indicate that ABP 501 is a highly similar
      alternative to adalimumab in terms of safety, efficacy, tolerability and
      immunogenicity. ABP 501 has already been approved by health authorities in Europe
      and the United States of America, as a subcutaneous (s.c.) therapy option for the
      treatment of patients with RA, but also for the full spectrum approved for its
      bio-originator adalimumab. Expert opinion: Current body of evidence suggests that
      all biologic activities have been demonstrated to be equivalent between ABP 501
      and the originator, including binding rates and affinity to TNF, and also the
      effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC).
      Therefore, it is fully expected to have same efficacy and safety in all
      indications.

PMID- 29350567
TI  - Pretreatment of ferulic acid attenuates inflammation and oxidative stress in a
      rat model of lipopolysaccharide-induced acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a fatal clinical condition that can
      be caused by pulmonary and non-pulmonary diseases. Oxidative stress and
      inflammation play key roles in the development of ARDS. In this study, we
      investigated whether ferulic acid (FA), an anti-oxidant, was beneficial for
      prophylaxis of ARDS. We established an ARDS rat model using lipopolysaccharide
      (LPS) administration. Lung injury was assessed by lung wet/dry ratio and broncho
      alveolar lavage fluid (BALF) analysis. Hematoxylin and eosin staining was
      performed to evaluate the histological changes of the lungs. Enzyme-linked
      immunosorbent assay (ELISA) and immunoblotting were performed to detect proteins
      in BALF and lung tissue, respectively. Pulmonary function was determined by
      testing the oxygen level in BALF. FA pretreatment significantly alleviated LPS
      induced pulmonary histological changes. FA reversed LPS-induced changes of lung
      wet/dry ratio, total protein in BALF, P(A-a)O2, and PaO2/FiO2. In addition, LPS
      dramatically up-regulated the secretion of interleukin (IL)-1beta, IL-6, tumor
      necrosis factor (TNF)-alpha, and IL-10 in BALF ( P < 0.01). However, pretreatment
      of FA significantly improved LPS-induced inflammation. We found that FA indeed
      reduced oxidative stress in the lungs by testing malondialdehyde level,
      myeloperoxidase level, and total anti-oxidant capacity. We also proved that FA
      inactivated multiple mitogen-activated protein kinase signaling pathways in the
      lungs. In conclusion, FA alleviated LPS-induced ARDS through its anti
      inflammatory and anti-oxidant activities.

PMID- 29350568
TI  - ABP 980: promising trastuzumab biosimilar for HER2-positive breast cancer.
AB  - INTRODUCTION: Approval of the HER2-targeted antibody trastuzumab dramatically
      improved outcomes for patients with HER2-positive breast cancer. Multiple
      trastuzumab biosimilars, including ABP 980, are in clinical development.
      Biosimilars are not identical to the reference biologic, but exhibit equivalence
      and safety in analytical and clinical studies. Areas covered: A brief
      introduction to trastuzumab, overview of trastuzumab biosimilars, and detailed
      review of ABP 980 preclinical and clinical studies are included. We searched
      PubMed and 2016-2017 ASCO and ESMO conference proceedings for 'ABP 980' or
      'trastuzumab biosimilar'. 'ABP 980 and breast cancer' or 'trastuzumab biosimilar
      and breast cancer' were used to search clinicaltrials.gov for phase III trials.
      Analytical studies of ABP 980 pharmacokinetics (PK) or pharmacodynamics (PD),
      phase I studies of ABP 980 safety and PK/PD, and phase III studies of clinical
      efficacy vs trastuzumab are included. Expert opinion: Questions remain regarding
      long-term impact of biosimilars on overall healthcare costs, insurance coverage
      of multiple approved biosimilars, and extensive clinical safety and efficacy
      follow-up. By producing a competitive market, trastuzumab biosimilars are
      anticipated to improve access to standard of care therapies, although real-world
      evidence remains to be obtained. Increased global access to HER2-targeted therapy
      may eventually alter the landscape of breast cancer and survival rates.

PMID- 29350569
TI  - Practice pearl: liraglutide and cardiovascular and renal events in type 2
      diabetes.
AB  - Review of: Marso S, Daniels G, Brown-Frandsen K, et al. Liraglutide and
      Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2016; 375: 311-322. Mann
      J, Orsted D, Brown-Frandsen K, et al. Liraglutide and Renal Outcomes in Type 2
      Diabetes. N Engl J Med 2017; 377: 839-848. This comprehensive research project,
      LEADER, led to two reports, one focusing on the effect of liraglutide on
      cardiovascular events, and the second one reporting on the renal effects on the
      same study population. The study group included 9340 patients with type 2
      diabetes. Patients were required to have type 2 diabetes and an age 50 with a
      previous cardiovascular problem or chronic heart failure, or an age of 60 with at
      least one cardiovascular risk factor. Patients were randomized to 1.8 mg (or the
      maximum tolerated dose) of liraglutide, or placebo. The median follow up was 3.8
      years. The primary cardiovascular outcome, a combined endpoint of death from
      cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, was
      seen in 13% (608 of 4668 patients) treated with liraglutide versus 14.9 % (694 of
      4672 patients) in the placebo patients (HR 0.87; 95% confidence interval [CI]
      0.78 to 0.97; P = 0.01 for superiority). Death from cardiovascular disease and
      death from any cause were also lower in the liraglutide group. The rates for
      nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart
      failure were not significantly reduced. In the renal report, the renal outcome
      was reduced in the liraglutide versus the placebo group (268 of 4668 versus 337
      out of 4672 in the placebo group; HR 0.78; CI 0.67 to 0.92; p = 0.003). This
      improvement was mainly driven by a lower rate of the new onset of persistent
      macroalbuminuria in the liraglutide patients (161 vs 215 patients; HR 0.74; 95%
      CI, 0.60 to 0.91; p = 0.004), while the rates of other renal adverse events were
      similar in both groups. When taken together these two reports are the first data
      to show that the glucagon-like peptide 1 (GLP-1) analogue liraglutide can reduce
      cardiovascular events and halt progression to macroalbuminuria in patients with
      Type 2 diabetes.

PMID- 29350570
TI  - Benefits of Laparoscopic Approach for Resection of Liver Tumors in Cirrhotic
      Patients.
AB  - INTRODUCTION: Liver resection in cirrhotic patients is associated with increased
      morbidity and mortality. The objective of this study was to compare short-term
      results of laparoscopic resection (LR) and open surgery (OS) for minor liver
      resection in patients with hepatocellular carcinoma (HCC) hepatocellularcarcinoma
      on nontumor cirrhotic liver (HCC/F4) and patients with colorectal cancer liver
      metastases (CRLMs) colorectal liver metastases on healthy liver (CRLM/F0).
      MATERIALS AND METHODS: Between January 2005 and December 2014, all patients
      undergoing liver resection (n = 754) were included in this study. Liver
      resections for cholangiocarcinoma or benign tumor, major liver resection (>=3
      segments), HCC on healthy liver, CRLM on cirrhotic liver, and liver resection
      with technically difficult accessibility (segments I, VII, and VIII) were
      excluded. The primary endpoint of the study was a validated composite endpoint
      (CEP), which included specific liver surgery complications (Clavien >=III),
      allowing comparison of the postoperative course after LR versus OR for HCC/F4
      patients and CRLM/F0 patients using propensity score (PS) analysis. Secondary
      endpoints were major postoperative morbidity according to the Clavien-Dindo
      classification (>=III) and intensive care unit (ICU) length of hospital stay
      (LOS) and overall LOS. The test group was defined as HCC/F4 patients operated by
      LR, and the control group was defined as HCC/F4 patients and CRLM/F0 patients
      operated by OS and CRLM/F0 patient operated by LR. RESULTS: Sixty patients
      (38.7%) underwent LR and 95 patients (61.3%) underwent OS. Surgery was performed
      for CRLM in 93 patients (60%) and for HCC in 62 patients (40%). No difference was
      demonstrated between HCC/F4 patients and CRLM/F0 patients in the LR group in
      terms of the CEP (7% versus 18.1%; P = .23), while a significant difference for
      the CEP was observed between HCC/F4 patients and CRLM/F0 patients after OS (50%
      versus 21%; P = .021). A higher rate of CEP was observed for HCC/F4 patients
      operated by OS compared to HCC/F4 patients operated by LR (50% versus 7.8%; P =
      .009). No significant difference in Clavien-Dindo score >=III was observed
      between HCC/F4 patients and CRLM/F0 patients operated by LR (10% versus 4.5%; P =
      .98). A higher postoperative ascites rate was observed for HCC/F4 patients
      operated by OS compared to CRLM/F0 patients operated by OS (25% versus 2.8%; P =
      .006). This difference was no longer observed when HCC/F4 patients were compared
      to CRLM/F0 operated by LR (7.8% versus 2.8%; P = .09). The postoperative
      mortality rate was 1.8% and was not correlated with nontumor liver or surgical
      approach. A shorter LOS was observed for HCC/F4 patients operated by LR compared
      to HCC/F4 patients operated by OS (7.53 versus 17.13; P = .011). CONCLUSION: The
      laparoscopic approach for malignant liver tumor is associated with a lower
      specific complication rate. LR for HCC/F4 could eliminate excess morbidity and
      decrease LOS in patients with cirrhotic liver.

PMID- 29350571
TI  - Intimate partner violence perpetration corresponds to a dorsal-ventral gradient
      in medial PFC reactivity to interpersonal provocation.
AB  - Intimate partner violence (IPV) perpetration is often preceded by perceived
      interpersonal provocations such as slights, insults, and rejections. Yet the
      neural mechanisms that link provocation to IPV remain unclear. In the context of
      interactions with strangers, the medial prefrontal cortex (MPFC) has been
      repeatedly shown to respond to provocation, with more dorsal activation
      associated with more aggressive reactions and more ventral activation associated
      with less aggressive reactions. We used functional brain imaging to test whether
      this dorsal-ventral MPFC reactivity gradient would also correlate with greater
      aggression towards an unexamined target: intimate partners. To do so, 61
      undergraduates (27.87% male, age range: 18-22) reported whether they had ever
      committed various acts of IPV perpetration (e.g., punching, hitting, shoving) and
      then were repeatedly provoked by a stranger while undergoing functional MRI
      (fMRI) scanning. Individuals with a disproportionately dorsal, rather than
      ventral, MPFC response were more likely to have perpetrated IPV and had
      perpetrated more kinds of IPV, even when controlling for gender. These findings
      provide further evidence that the dorsal-ventral MPFC gradient is a critical,
      biological indicator of whether an individual is more or less likely to react
      aggressively and suggest new avenues for understanding and potentially preventing
      IPV perpetration.

PMID- 29350572
TI  - Semantic language deficit developing following herpes simplex encephalitis:
      reorganization "cannibalising" language centers?
AB  - Herpes simplex virus encephalitis (HSVE) commonly presents with severe amnesia
      due to virus-mediated destruction of key regions in the temporal lobes, although
      language and executive impairment has been described. Little is known however of
      the long-term cognitive changes in these patients, including changes that may
      happen with cortical reorganization. We describe a patient with HSVE who
      presented with a highly unusual late-onset language syndrome, which may reflect
      distal cortical changes after her original injury.

PMID- 29350573
TI  - Feasibility and Acceptability of Screening for Adverse Childhood Experiences in
      Prenatal Care.
AB  - INTRODUCTION: Adverse childhood experiences (ACEs) are common among pregnant
      women and contribute to increased risk for negative perinatal outcomes, yet few
      clinicians screen prenatal patients for ACEs. The purpose of this study was to
      evaluate the feasibility and acceptability of screening for ACEs in standard
      prenatal care. METHODS: We evaluated a 4-month pilot (March 2016-June 2016) to
      screen pregnant women (at ~14-23 weeks of gestation) for ACEs and resiliency in
      two Kaiser Permanente Northern California medical centers (N = 480). We examined
      the acceptability of the screening to patients through telephone surveys (N =
      210) and to clinicians through surveys and focus groups (N = 26). RESULTS: Most
      eligible patients (78%) were screened. Patients who received the screening were
      significantly more likely to be non-Hispanic White, Asian, or of "Other" or
      "Unknown" race/ethnicity than African American or Hispanic race/ethnicity (p =
      0.02). Among those screened, 88% completed the questionnaires; 54% reported 0
      ACEs, 28% reported 1-2 ACEs, and 18% reported >=3 ACEs. Most patients were
      somewhat or very comfortable completing the questionnaires (91%) and discussing
      ACEs with their clinician (93%), and strongly or somewhat strongly agreed that
      clinicians should ask their prenatal patients about ACEs (85%). Clinicians
      reported significant pre- to postpilot increases in comfort discussing ACEs,
      providing education, and offering resources (ps < 0.01). Clinicians' willingness
      to screen for ACEs was contingent on adequate training, streamlined workflows,
      inclusion of resilience screening, and availability of mental health, parenting,
      and social work resources. CONCLUSION: ACEs screening as part of standard
      prenatal care is feasible and generally acceptable to patients. Women's health
      clinicians are willing to screen patients for ACEs when appropriately trained and
      adequate behavioral health referral resources are available.

PMID- 29350574
TI  - Dr. William Gerald Dyer.

PMID- 29350575
TI  - The neural substrates of improved phonological processing following successful
      treatment in a case of phonological alexia and agraphia.
AB  - Phonological deficits are common in aphasia after left-hemisphere stroke, and can
      have significant functional consequences for spoken and written language. While
      many individuals improve through treatment, the neural substrates supporting
      improvements are poorly understood. We measured brain activation during
      pseudoword reading in an individual through two treatment phases. Improvements
      were associated with greater activation in residual left dorsal language regions
      and bilateral regions supporting attention and effort. Gains were maintained,
      while activation returned to pre-treatment levels. This case demonstrates the
      neural support for improved phonology after damage to critical regions and that
      improvements may be maintained without markedly increased effort.

PMID- 29350576
TI  - Posterior reversible encephalopathy syndrome in stroke-prone spontaneously
      hypertensive rats on high-salt diet.
AB  - Stroke-prone spontaneously hypertensive rats (SHRSP) on high-salt diet are
      characterized by extremely high arterial pressures, and have been endorsed as a
      model for hypertensive small vessel disease and vascular cognitive impairment.
      However, rapidly developing malignant hypertension is a well-known cause of
      posterior reversible encephalopathy syndrome (PRES) in humans, associated with
      acute neurological deficits, seizures, vasogenic cerebral edema and
      microhemorrhages. In this study, we aimed to examine the overlap between human
      PRES and SHRSP on high-salt diet. In SHRSP, arterial blood pressure progressively
      increased after the onset of high-salt diet and seizure-like signs emerged within
      three to five weeks. MRI revealed progressive T2-hyperintense lesions suggestive
      of vasogenic edema predominantly in the cortical watershed and white matter
      regions. Histopathology confirmed severe blood-brain barrier disruption, white
      matter vacuolization and microbleeds that were more severe posteriorly.
      Hematological data suggested a thrombotic microangiopathy as a potential
      underlying mechanism. Unilateral common carotid artery occlusion protected the
      ipsilateral hemisphere from neuropathological abnormalities. Notably, all MRI and
      histopathological abnormalities were acutely reversible upon switching to regular
      diet and starting antihypertensive treatment. Altogether our data suggest that
      SHRSP on high-salt diet recapitulates the neurological, histopathological and
      imaging features of human PRES rather than chronic progressive small vessel
      disease.

PMID- 29350577
TI  - Serial Palliative Performance Scale Assessment in a University General Hospital:
      A Pilot Study.
AB  - BACKGROUND: Serial Palliative Performance Scale (PPS) assessments may predict
      functional decline and prognosis in cancer and noncancer patients and help with
      end-of-life decision making. OBJECTIVE: To evaluate the functional status of
      using serial PPS assessments of patients being assisted in collaboration with the
      palliative care team (PCT). DESIGN: Prospective cohort pilot study. MEASUREMENTS:
      The sample consisted of 64 cancer and noncancer inpatients being assisted in
      collaboration with the PCT during the period from 2012 to 2016 (included 12
      months). Patients' PPS scores were assessed in three sequential stages:
      prehospital, first PCT assessment, and outcome (discharge, transference to
      another unit or death). Functional performance was classified in categories as
      stable (PPS scores between 70% and 100%), transitional (PPS scores between 40%
      and 60%), and end of life (PPS scores between 10% and 30%). RESULTS: The mean PPS
      score during the three assessment stages (respectively, 60.5%, 38.9%, and 25.9%)
      was significantly different (p < 0.001). Cancer patients had higher PPS scores
      than noncancer patients; however, both groups exhibited a functional decline
      along the hospital stay. In both groups there was a negative correlation between
      the time frame between the different assessment stages and PPS scores
      (respectively, Pearson -0.4 and -0.6; p < 0.01). The survival curve of the first
      palliative assessment stage demonstrated earlier death in patients in the end-of
      life category. CONCLUSION: Serial PPS assessments are feasible and predicted
      functional decline in cancer and noncancer patients in this sample. Cancer
      patients exhibited higher initial functional scores but both cancer and noncancer
      patients declined in functionality along hospitalization. Earlier deaths occurred
      in the terminal PPS category than in the transitional PPS category.

PMID- 29350578
TI  - The impact of gender on asthma in the daily clinical practice.
AB  - OBJECTIVES: It is up-to-date to consider the potential gender impact on a
      disease. There are few data about gender difference in asthma. Therefore, the
      present cross-sectional study tested this hypothesis in a real-life setting to
      investigate possible difference between genders. METHODS: This study was cross
      sectional, considering 554 consecutive outpatients suspected of asthma, who were
      referred for a first specialist visit. Clinical and functional parameters were
      evaluated. RESULTS: Females with asthma could have a worse perception of asthma
      control, assessed by asthma control test (ACT), and more anxiety than asthmatic
      males. However, there was no difference regarding asthma control grading, asthma
      severity, and asthma medication use between genders; the differences in lung
      function were without clinical relevance. CONCLUSIONS: In the daily clinical
      practice, it is relevant to consider gender in the management of asthma.

PMID- 29350580
TI  - Development and Evaluation of a Yoga Intervention Program for Parkinson's
      Disease.
AB  - Preliminary research indicates that yoga could be a valuable tool for people
      suffering from Parkinson's disease (PD). However, little has been published about
      the process by which the yoga interventions were designed and evaluated. This
      study elaborates on the process of developing and testing a bi-weekly, 12-week
      yoga program to determine its safety and feasibility for people with PD. The lead
      yoga teacher used input from a focused literature review to design an initial
      draft of the intervention program. This draft was reviewed by a group of yoga
      experts ( n = 6) to develop the final intervention program. This 12-week
      intervention was implemented in 19 participants with PD (mean age 63 +/- 8, range
      49-75) via twice-weekly yoga classes. Through this comprehensive development
      process, a series of 24 individual 1-hour yoga sequences was created. These
      sequences included yoga postures (asana), breathing techniques (pranayama), and
      mindfulness meditation principles specifically chosen to address concerns unique
      to the PD population. The feasibility of the program was supported with excellent
      attendance: 90% of participants attended > 75% of the classes, with four
      participants attending 100%. No adverse events were reported. This development
      process produced a safe and enjoyable yoga program specific for the needs of
      people with PD. However, this methodology could serve as a template for future
      studies on how to develop safe and effective yoga interventions for other
      populations.

PMID- 29350579
TI  - Evaluation of respiratory motion-corrected cone-beam CT at end expiration in
      abdominal radiotherapy sites: a prospective study.
AB  - BACKGROUND: Cone beam computed tomography (CBCT) for radiotherapy image guidance
      suffers from respiratory motion artifacts. This limits soft tissue visualization
      and localization accuracy, particularly in abdominal sites. We report on a
      prospective study of respiratory motion-corrected (RMC)-CBCT to evaluate its
      efficacy in localizing abdominal organs and improving soft tissue visibility at
      end expiration. MATERIAL AND METHODS: In an IRB approved study, 11 patients with
      gastroesophageal junction (GEJ) cancer and five with pancreatic cancer underwent
      a respiration-correlated CT (4DCT), a respiration-gated CBCT (G-CBCT) near end
      expiration and a one-minute free-breathing CBCT scan on a single treatment day.
      Respiration was recorded with an external monitor. An RMC-CBCT and an uncorrected
      CBCT (NC-CBCT) were computed from the free-breathing scan, based on a respiratory
      model of deformations derived from the 4DCT. Localization discrepancy was
      computed as the 3D displacement of the GEJ region (GEJ patients), or gross tumor
      volume (GTV) and kidneys (pancreas patients) in the NC-CBCT and RMC-CBCT relative
      to their positions in the G-CBCT. Similarity of soft-tissue features was measured
      using a normalized cross correlation (NCC) function. RESULTS: Localization
      discrepancy from the end-expiration G-CBCT was reduced for RMC-CBCT compared to
      NC-CBCT in eight of eleven GEJ cases (mean +/- standard deviation, respectively,
      0.21 +/- 0.11 and 0.43 +/- 0.28 cm), in all five pancreatic GTVs (0.26 +/- 0.21
      and 0.42 +/- 0.29 cm) and all ten kidneys (0.19 +/- 0.13 and 0.51 +/- 0.25 cm).
      Soft-tissue feature similarity around GEJ was higher with RMC-CBCT in nine of
      eleven cases (NCC =0.48 +/- 0.20 and 0.43 +/- 0.21), and eight of ten kidneys
      (0.44 +/- 0.16 and 0.40 +/- 0.17). CONCLUSIONS: In a prospective study of motion
      corrected CBCT in GEJ and pancreas, RMC-CBCT yielded improved organ visibility
      and localization accuracy for gated treatment at end expiration in the majority
      of cases.

PMID- 29350581
TI  - Characteristics of Yoga Practice and Predictors of Practice Frequency.
AB  - Yoga is a globally popular mind-body practice used for health. The objective of
      this study was to characterize yoga practice and factors associated with
      frequency of practice. Yoga practitioners were sent invitations via email to
      participate in an online survey. Yoga characteristics and other sociodemographics
      were collected. Data from 309 consenting respondents were analyzed for patterns
      in practice characteristics (yoga techniques, location of practice, method of
      instruction, teacher status, and yoga type). Associations between characteristics
      of practice and yoga practice frequency were computed. The following
      characteristics were then analyzed as predictors of practice frequency in a
      regression model: location of practice, method of instruction, teacher status,
      yoga type, and techniques. Most respondents reported use of all three yoga
      techniques (movements, breathing, and meditation) and practiced an average of 4.5
      +/- 1.9 days a week. Key characteristics such as location of practice, method of
      instruction, and frequency significantly differed by teacher status and by yoga
      type (Viniyoga practitioners vs. other yoga styles). In our regression model,
      being a yoga teacher, being taught a one-on-one yoga practice by someone else,
      and regular use of movement were positively associated with increased practice
      frequency. Our analyses provide insight into how yoga factors such as teacher
      status, method of instruction, and use of tools relate to practice frequency.
      Understanding the relationships between practice characteristics and practice
      frequency may allow for the improved implementation of yoga for health.

PMID- 29350582
TI  - The repeated name penalty effect in children's natural reading: Evidence from eye
      tracking.
AB  - We report data from an eye tracking experiment on the repeated name penalty
      effect in 9-year-old children and young adults. The repeated name penalty effect
      is informative for the study of children's reading because it allows conclusions
      about children's ability to direct attention to discourse-level processing cues
      during reading. We presented children and adults simple three-sentence stories
      with a single referent, which was referred to by an anaphor-either a pronoun or a
      repeated name-downstream in the text. The anaphor was either near or far from the
      antecedent. We found a repeated name penalty effect in early processing for
      children as well as adults, suggesting that beginning readers are already
      susceptible to discourse-level expectations of anaphora during reading.
      Furthermore, children's reading was more influenced by the distance of anaphor
      and antecedent than adults', which we attribute to differences in reading fluency
      and the resulting cognitive load during reading.

PMID- 29350583
TI  - Morphological structure mediates the notional meaning of gender marking: Evidence
      from the gender-congruency effect in Hebrew speech production.
AB  - This study investigated the gender-congruency effect of animate nouns in Hebrew.
      The Picture-Word Interference paradigm was used to manipulate gender congruency
      between target pictures and spoken distractors. Naming latency revealed an
      inhibitory gender-congruency effect, as naming the pictures took longer in the
      presence of a gender-congruent distractor than with a distractor from a different
      gender category. The inhibitory effect was demonstrated for feminine
      (morphologically marked) nouns, across two stimulus-onset asynchronies (SOAs)
      (Experiments 1a and 1b), and masculine (morphologically unmarked) nouns
      (Experiment 2). The same pattern was observed when participants had to produce
      bare nouns (Experiment 1) or gender-marked noun phrases (Experiment 3). The
      inhibitory pattern of the effect resembles previous findings of bare nouns in a
      subset of Romance languages, including Italian and Spanish. These findings add to
      previous research which investigated the gender-congruency effect of inanimate
      nouns, where no effect of gender-congruent words was found. The results are
      discussed in relation to the null effect previously found for inanimate nouns.
      The comparison of the present and previous studies is motivated by a common
      linguistic distinction between animate and inanimate nouns in Hebrew, which
      ascribes grammatical gender specifications to derivational structures (for
      inanimate nouns) versus inflectional structures (for animate nouns). Given the
      difference in the notional meaning of gender specification for animate and
      inanimate nouns, the case of Hebrew exemplifies how language-specific
      characteristics, such as rich morphological structures, can be used by the
      linguistic system to express conceptual distinctions at the form-word level.

PMID- 29350584
TI  - Developing standard operating procedures for gene drive research in disease
      vector mosquitoes.
AB  - Numerous arthropod species represent potential targets for gene-drive-based
      population suppression or replacement, including those that transmit diseases,
      damage crops, or act as deleterious invasive species. Containment measures for
      gene drive research in arthropods have been discussed in the literature, but the
      importance of developing safe and effective standard operating procedures (SOPs)
      for these types of experiments has not been adequately addressed. Concisely
      written SOPs link safe work practices, containment measures, institutional
      training, and research-specific protocols. Here we discuss information to be
      considered by principal investigators, biosafety officers, and institutional
      biosafety committees as they work together to develop SOPs for experiments
      involving gene drive in arthropods, and describe various courses of action that
      can be used to maintain the effectiveness of SOPs through evaluation and
      revision. The information provided herein will be especially useful to
      investigators and regulatory personnel who may lack extensive experience working
      with arthropods under containment conditions.

PMID- 29350585
TI  - Isolation of active coagulant protein from the seeds of Strychnos potatorum - a
      potential water treatment agent.
AB  - The application of natural coagulants for decentralized water treatment is
      gaining importance as a part of global sustainable initiative. This study focuses
      on the isolation of active coagulation components responsible for water
      clarification with respect to Strychnos potatorum seeds. The active coagulant
      components, protein and polysaccharide, were successfully isolated, dialysed and
      subjected to gel permeation chromatography. The polysaccharide was isolated with
      the saline extraction method and characterized using FTIR and NMR spectroscopy.
      Protein was precipitated with 80% ammonium sulphate solution combined with
      dialysis and gel permeation chromatography using Sephadex G-50. SDS-PAGE revealed
      that the isolated protein has a molecular weight of 12 kDa. The small-scale
      coagulation assay suggests that the protein fraction has superior coagulation
      activity than the isolated polysaccharide residue. The active coagulant fractions
      reported in this study would be helpful in deploying cheaper and simple methods
      in scaling up the coagulant fraction from these seeds acting as a potential water
      treatment agent.

PMID- 29350586
TI  - Mass media representations of the evidence as a possible deterrent to
      recommending exercise for the treatment of depression: Lessons five years after
      the extraordinary case of TREAD-UK.
AB  - Exercise or physical activity are recommended options within stepped-care
      treatment models for depression. However, few physicians present these options to
      patients, in part because of the impression that the supporting evidence is weak
      or inconsistent. We speculate that the coocurrence of "counter-messaging" and
      deficient critical appraisal may lead to such impressions. We focus on TREAD-UK
      (ISRCTN16900744), the largest trial to investigate "whether physical activity can
      be an effective treatment for depression within primary care". In media
      statements, researchers declared that exercise was ineffective in lowering
      depression. We examined (a) the results of the trial, critiques, and rejoinders,
      (b) the impact on internet searches, and (c) whether TREAD-UK was critically
      appraised, as reflected in citing articles. We show that the results of TREAD-UK
      were misrepresented. The media campaign resulted in a fourfold increase in
      relevant internet searches. Of articles characterising the results, 57% adopted
      the interpretation that exercise failed to lower depression, whereas only 17%
      were critiques. We identify similarities to media portrayals of the OPERA
      (ISRCTN43769277), DEMO (NCT00103415), and DEMO-II trials (NCT00695552). We note a
      disconcerting trend of media campaigns that misrepresent the effects of exercise
      on depression and call for increased scrutiny in peer reviewing both pre- and
      post-publication.

PMID- 29350587
TI  - Recent advances in 3D bioprinting for the regeneration of functional cartilage.
AB  - The field of regeneration for functional cartilage has progressed tremendously.
      Conventional approaches for regenerating the damaged tissue based on integrated
      manufacturing are limited by their inability to produce precise and customized
      biomimetic tissues. On the other hand, 3D bioprinting is a promising technique
      with increased versatility because it can co-deliver cells and biomaterials with
      proper compositions and spatial distributions. In the present article, we review
      recent progress in the complete 3D printing process involved in functional
      cartilage regeneration, including printing techniques, biomaterials and cells. We
      also discuss the combination of 3D in vivo hybrid bioprinting with spheroids,
      gene delivery strategies and zonal cartilage design as a future direction of
      cartilage regeneration research.

PMID- 29350588
TI  - Arguments against the role of cortical spreading depression in migraine.
AB  - Cortical spreading depression (CSD) is a wave of increased electrocortical
      activity and vasodilation, followed by sustained decreased activity and prolonged
      vasoconstriction. Although the discovery of CSD has been ascribed to Leao, rather
      than vasoconstriction, he only observed a depression of neural activity combined
      with vasodilation, with much weaker stimulation than used by his followers. There
      is a longstanding belief that CSD underlies migraine aura, with its positive
      symptoms such as mosaic patterns and its negative symptoms such as scotoma, and a
      similar propagation speed and vasoreaction pattern. However, there are many
      arguments against this theory. CSD is difficult to evoke in man, and
      electroencephalography (EEG) readings are not flattened during migraine (as
      opposed to EEG during CSD). Moreover, in contrast to CSD, migraine can occur
      bilaterally, and is not accompanied by a disrupted blood-brain barrier, increased
      cerebral metabolism, or cerebral cell swelling. Calcitonin gene-related peptide,
      which is thought to be characteristic of migraine pain, is increased in the blood
      from the external jugular vein during migraine in humans, but not during CSD in
      cats or rats. Moreover, CSD does not explain the appearance of premonitory
      symptoms or allodynia, long before the actual onset of aura. In addition, there
      is a variation in the pain mechanisms of migraine and CSD, and in their reaction
      to transcranial magnetic stimulation and several pharmacologic interventions.
      Finally, the origin of putative CSD in migraine is currently unknown.

PMID- 29350589
TI  - Epidemiological Investigation and Genotype of Chlamydia Exposure in Pigeons in
      Three Provinces in Northern China.
AB  - Chlamydia is considered as one of the most widely prevalent zoonotic pathogens.
      It can spread from infected birds to human beings through direct or indirect
      contact with fecal shedding of Chlamydia. However, data concerning prevalence and
      genotypes of Chlamydia in pigeons are limited. In the present study, a total of
      963 serum samples was collected from Jilin Province, Liaoning Province, and Inner
      Mongolia Autonomous Region (IMAR) in China between August 2015 and December 2016
      and the seroprevalence for Chlamydia was analyzed by indirect hemagglutination
      assay test. The seroprevalence of Chlamydia was 20.4% (215/963) in total, at the
      cutoff 1:16, with the titers of 1:16 in 109, 1:64 in 49, 1:256 in 38, and 1:1024
      in 18. Samples from all six administrative cities were detected Chlamydia
      seropositive, ranging from 19.0% to 25.0%. Adult pigeons (23.5%) have a
      significant higher seroprevalence than juveniles (15.2%). Four PCR-positive
      samples represented Chlamydia psittaci genotype B. This is the first report of
      Chlamydia infection in pigeons in Liaoning Province and IMAR. The occurrence of
      C. psittaci genotype B in the droppings of pigeons suggests potential
      environmental contamination with C. psittaci and may raise a public health
      concern.

PMID- 29350590
TI  - Human genetics and molecular mechanisms of vein of Galen malformation.
AB  - Vein of Galen malformations (VOGMs) are rare developmental cerebrovascular
      lesions characterized by fistulas between the choroidal circulation and the
      median prosencephalic vein. Although the treatment of VOGMs has greatly benefited
      from advances in endovascular therapy, including technical innovation in
      interventional neuroradiology, many patients are recalcitrant to procedural
      intervention or lack accessibility to specialized care centers, highlighting the
      need for improved screening, diagnostics, and therapeutics. A fundamental
      obstacle to identifying novel targets is the limited understanding of VOGM
      molecular pathophysiology, including its human genetics, and the lack of an
      adequate VOGM animal model. Herein, the known human mutations associated with
      VOGMs are reviewed to provide a framework for future gene discovery. Gene
      mutations have been identified in 2 Mendelian syndromes of which VOGM is an
      infrequent but associated phenotype: capillary malformation-arteriovenous
      malformation syndrome ( RASA1) and hereditary hemorrhagic telangiectasia ( ENG
      and ACVRL1). However, these mutations probably represent only a small fraction of
      all VOGM cases. Traditional genetic approaches have been limited in their ability
      to identify additional causative genes for VOGM because kindreds are rare,
      limited in patient number, and/or seem to have sporadic inheritance patterns,
      attributable in part to incomplete penetrance and phenotypic variability. The
      authors hypothesize that the apparent sporadic occurrence of VOGM may frequently
      be attributable to de novo mutation or incomplete penetrance of rare transmitted
      variants. Collaboration among treating physicians, patients' families, and
      investigators using next-generation sequencing could lead to the discovery of
      novel genes for VOGM. This could improve the understanding of normal vascular
      biology, elucidate the pathogenesis of VOGM and possibly other more common
      arteriovenous malformation subtypes, and pave the way for advances in the
      diagnosis and treatment of patients with VOGM.

PMID- 29350591
TI  - Clip ligation for ruptured intracranial aneurysm in a child with Loeys-Dietz
      syndrome: case report.
AB  - The authors present the case of a pediatric patient with Loeys-Dietz syndrome
      (LDS) who underwent craniotomy for clip ligation of a ruptured intracranial
      aneurysm. To the authors' knowledge, this is the youngest reported patient with
      LDS who has been treated for a ruptured intracranial aneurysm. The patient
      presented with aneurysmal subarachnoid hemorrhage even though the results of
      surveillance screening were negative, and the aneurysm arose from the wall of the
      parent artery away from an arterial branch point. She was treated with open clip
      ligation and recovered well. The authors review the other reported cases of
      treated intracranial aneurysms in patients with LDS.

PMID- 29350592
TI  - Geographic proximity to specialized pediatric neurosurgical care in the
      contiguous United States.
AB  - OBJECTIVE Absent from an analysis of supply is consideration of the geographic
      distribution of pediatric neurosurgeons. Several patient socioeconomic metrics
      are known to be associated with outcome in pediatric neurosurgical diseases, such
      as hydrocephalus. The purpose of this study was to determine current geographic
      proximity to pediatric neurosurgical care using professional society databases.
      This study also sought to establish how socioeconomic factors are related to
      distance to care, using federal government-collected data. METHODS A list of
      currently practicing American Board of Pediatric Neurological Surgery (ABPNS)
      certified neurosurgeons was compiled (ABPNS group). A separate list of practicing
      members of the Joint Pediatric Section (JPS) of the American Association of
      Neurological Surgeons/Congress of Neurological Surgeons was prepared (JPS group).
      Current primary practice locations were collected from each professional society
      database for each ABPNS or JPS neurosurgeon and were charted using ArcGIS mapping
      software (ESRI, version 10.3) on a United States Census Bureau map. The straight
      distance from the centroid of each zip code tabulation area (ZCTA) to the nearest
      neurosurgeon was determined by group type of neurosurgeon (ABPNS vs ABPNS + JPS).
      ZCTA-level data on demographic and socioeconomic factors were acquired from the
      American Community Survey, including data in children and young adults (0-18 or 0
      24 years old) and the general population. These data were compared by distance to
      care and by groups of neurosurgeons (Pearson's chi-square analysis; the threshold
      of significance was set at 0.05). RESULTS Three hundred fifty-five practicing
      neurosurgeons providing pediatric care were located, of whom 215 surgeons were
      certified by the ABPNS and 140 were JPS members only. The analysis showed that 1
      pediatric neurosurgeon is in practice for every 289,799 persons up to the age of
      24 years. The average distance between a ZCTA and the nearest pediatric
      neurosurgeon is 63.3 miles (SE 0.3, range 0.0-499.7 miles). Geographic analysis
      showed that 27.1% of children live farther than 60 miles from an ABPNS-certified
      neurosurgeon and 19.7% from either an ABPNS-certified neurosurgeon or a JPS
      member. ZCTAs with children who live farther than 60 miles from a neurosurgeon
      providing pediatric care had a marginally higher rate of uninsured children, a
      higher percentage of families with children living below the federal poverty
      level, and a higher proportion of persons living in rural areas compared with
      ZCTAs with children who live within 60 miles of care (p < 0.005 for each
      finding). CONCLUSIONS The results of this study indicate that there is
      considerable variation in proximity to pediatric neurosurgical subspecialty care
      by geographic region. In addition, there is a relationship between distance to
      neurosurgical care and socioeconomic indicators. Optimization of access to
      pediatric neurosurgical care may involve strategies to overcome long geographic
      distances, particularly in rural and underserved areas. Such areas may have
      disproportionately lower socioeconomic levels, which may further limit access to
      care and affect outcomes. Both the total number of pediatric neurosurgeons per
      pediatric population and their geographic distribution could be important in
      determining appropriate subspecialty supply factors (e.g., the number of
      accredited pediatric neurosurgical fellowship training programs), as well as
      being important drivers of neurosurgical patient outcomes.

PMID- 29350593
TI  - The natural history of complete spinal cord injury: a pooled analysis of 1162
      patients and a meta-analysis of modern data.
AB  - OBJECTIVE The natural history of complete spinal cord injury (SCI) is poorly
      studied. The classically quoted rate of improvement or conversion for patients
      with American Spinal Injury Association (ASIA) grade A (ASIA A) injuries is 15%
      20%; however, data supporting this rate are very limited. In this paper, the
      authors conducted a meta-analysis of modern data reporting on ASIA A patients and
      evaluated factors affecting the natural history of the disease. METHODS The
      authors conducted a systematic literature review of all randomized clinical
      trials (RCTs) and observational studies of patients with traumatic SCI. The
      Embase, MEDLINE, PubMed, Scopus, CINAHL, and Cochrane databases were reviewed for
      all studies reporting on SCI and published after 1992. A meta-analysis was
      conducted using the DerSimonian and Laird (random-effects) model with a summary
      odds ratio analysis. RESULTS Eleven RCTs and 9 observational studies were
      included in the final analysis. Overall, the 20 included studies reported on 1162
      patients with ASIA A injuries. The overall conversion rate was 28.1%, with 327 of
      1162 patients improving to at least ASIA B. The overall rate of conversion noted
      in cervical spine injuries was 33.3%, whereas that in thoracic injuries was
      30.6%. Patients undergoing early surgery had a higher rate of conversion (46.1%)
      than patients undergoing late surgery (25%) (OR 2.31, 95% CI 1.08-4.96, p =
      0.03). CONCLUSIONS The overall rate of conversion of ASIA A SCIs from pooled data
      of prospective trials and observational series is 28.1%. This rate of conversion
      is higher than what is reported in the literature. Early surgery is predictive of
      a higher conversion rate. However, there are not enough data to provide
      conclusions pertaining to the efficacy of biological and medical therapies.

PMID- 29350594
TI  - Determinants of perioperative transfusion risk in patients with adult spinal
      deformity.
AB  - OBJECTIVE To determine predictors of perioperative allogeneic packed red blood
      cell (pRBC) transfusion requirement (total units transfused) in patients with
      adult spinal deformity (ASD). METHODS The authors retrospectively analyzed
      records of patients aged 18 years or older who underwent surgical correction of
      ASD that involved 4 or more spinal levels by the same spine surgeon between 2010
      and 2016. Data regarding patient characteristics, comorbidities, surgical
      factors, and perioperative transfusions (up to 10 days after surgery) were
      analyzed using a linear regression model. Significance was set at p < 0.05.
      RESULTS The authors analyzed 165 patients (118 women) with a mean (+/- SD) age of
      61 +/- 12 years. Three-column osteotomies were associated with a mean
      intraoperative transfusion volume of 1.74 additional units of pRBCs. Each unit of
      intraoperatively salvaged blood used was associated with a mean 0.39-U increase
      in postoperative transfusion volume (p = 0.031). Every unit of allogeneic blood
      transfused intraoperatively was associated with a mean 0.23-U decrease in
      postoperative transfusion volume (p = 0.001). A preoperative hemoglobin
      concentration of 11.5 g/dl or more was associated with significantly fewer units
      transfused intraoperatively; a preoperative hemoglobin concentration of 14.0 g/dl
      or more was associated with fewer units transfused postoperatively. A history of
      smoking and intraoperative antifibrinolytic use were associated with increased
      and decreased numbers of units transfused postoperatively, respectively.
      CONCLUSIONS Effective blood management is key to perioperative care of patients
      with ASD. Three-column osteotomies were associated with a greater number of units
      of blood transfused. When considering postoperative transfusion requirements,
      surgeons should note that intraoperative blood salvage might be inferior to
      intraoperative allogeneic blood transfusion. Using antifibrinolytics and
      increasing the preoperative hemoglobin concentration to 11.5 g/dl or more are
      strategies for decreasing the need for perioperative transfusion. A history of
      smoking is a risk factor for postoperative transfusion requirement (total units
      transfused).

PMID- 29350595
TI  - Motor network recovery in patients with chronic spinal cord compression: a
      longitudinal study following decompression surgery.
AB  - OBJECTIVE The authors used functional MRI to assess cortical reorganization of
      the motor network after chronic spinal cord compression and to characterize the
      plasticity that occurs following surgical intervention. METHODS A 3-T MRI scanner
      was used to acquire functional images of the brain in 22 patients with reversible
      cervical spinal cord compression and 10 control subjects. Controls performed a
      finger-tapping task on 3 different occasions (baseline, 6-week follow-up, and 6
      month follow-up), whereas patients performed the identical task before surgery
      and again 6 weeks and 6 months after spinal decompression surgery. RESULTS After
      surgical intervention, an increased percentage blood oxygen level-dependent
      signal and volume of activation was observed within the contralateral and
      ipsilateral motor network. The volume of activation of the contralateral primary
      motor cortex was associated with functional measures both at baseline (r = 0.55,
      p < 0.01) and 6 months after surgery (r = 0.55, p < 0.01). The percentage blood
      oxygen level-dependent signal of the ipsilateral supplementary motor area 6
      months after surgery was associated with increased function 6 months after
      surgery (r = 0.48, p < 0.01). CONCLUSIONS Plasticity of the contralateral and
      ipsilateral motor network plays complementary roles in maintaining neurological
      function in patients with spinal cord compression and may be critical in the
      recovery phase following surgery.

PMID- 29350596
TI  - Enhancement of antitumor activity by using 5-ALA-mediated sonodynamic therapy to
      induce apoptosis in malignant gliomas: significance of high-intensity focused
      ultrasound on 5-ALA-SDT in a mouse glioma model.
AB  - OBJECTIVE High invasiveness of malignant gliomas frequently causes early local
      recurrence of the tumor, resulting in extremely poor outcome. To control such
      recurrence, novel therapies targeted toward infiltrating glioma cells around the
      tumor border are required. Here, the authors investigated the antitumor activity
      of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic
      acid (5-ALA), on malignant gliomas to explore the possibility for clinical use of
      5-ALA-mediated SDT (5-ALA-SDT). METHODS In vitro cytotoxicity of 5-ALA-SDT was
      evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells.
      Treatment-related apoptosis was analyzed using flow cytometry and TUNEL staining.
      Intracellular reactive oxygen species (ROS) were measured and the role of ROS in
      treatment-related cytotoxicity was examined by analysis of the effect of
      pretreatment with the radical scavenger edaravone. Effects of 5-ALA-SDT with high
      intensity focused ultrasound (HIFU) on tumor growth, survival of glioma
      transplanted mice, and histological features of the mouse brains were
      investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell
      morphology, inducing cell shrinkage, vacuolization, and swelling. Flow cytometric
      analysis and TUNEL staining indicated that 5-ALA-SDT induced apoptotic cell death
      in all gliomas. The 5-ALA-SDT generated significantly higher ROS than in the
      control group, and inhibition of ROS generation by edaravone completely
      eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT
      with HIFU greatly prolonged survival of the tumor-bearing mice compared with that
      of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly
      necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor
      cells in the perifocus area around the target of the HIFU-irradiated field. The
      proliferative activity of the entire tumor was markedly decreased. Normal brain
      tissues around the ultrasonic irradiation field of HIFU remained intact.
      CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of
      ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT
      with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus
      area of the HIFU-irradiated field, whereas the surrounding brain tissue remained
      normal, resulting in longer survival of the HIFU-treated mice compared with that
      of untreated mice. These results suggest that 5-ALA-SDT with HIFU may present a
      less invasive and tumor-specific therapy, not only for a tumor mass but also for
      infiltrating tumor cells in malignant gliomas.

PMID- 29350597
TI  - Letter to the Editor. Rendering unto Caesar: mini-pterional and mini
      orbitozygomatic approaches.

PMID- 29350598
TI  - Diffusion tensor imaging and ventricle volume quantification in patients with
      chronic shunt-treated hydrocephalus: a matched case-control study.
AB  - OBJECTIVE The object of this study was to use diffusion tensor imaging (DTI) and
      tract-based spatial statistics (TBSS) to characterize the long-term effects of
      hydrocephalus and shunting on white matter integrity and to investigate the
      relationship of ventricular size and alterations in white matter integrity with
      headache and quality-of-life outcome measures. METHODS Patients with shunt
      treated hydrocephalus and age- and sex-matched healthy controls were recruited
      into the study and underwent anatomical and DTI imaging on a 3-T MRI scanner. All
      patients were clinically stable, had undergone CSF shunt placement before 2 years
      of age, and had a documented history of complaints of headaches. Outcome was
      scored based on the Headache Disability Inventory and the Hydrocephalus Outcome
      Questionnaire. Fractional anisotropy (FA) and other DTI-based measures (axial,
      radial, and mean diffusivity; AD, RD, and MD, respectively) were extracted in the
      corpus callosum and internal capsule with manual region-of-interest delineation
      and in other regions with TBSS. Paired t-tests, corrected with a 5% false
      discovery rate, were used to identify regions with significant differences
      between patients and controls. Within the patient group, linear regression models
      were used to investigate the relationship between FA or ventricular volume and
      outcome, as well as the effect of shunt-related covariates. RESULTS Twenty-one
      hydrocephalus patients and 21 matched controls completed the study, and their
      data were used in the final analysis. The authors found significantly lower FA
      for patients than for controls in 20 of the 48 regions, mostly posterior white
      matter structures, in periventricular as well as more distal tracts. Of these 20
      regions, 17 demonstrated increased RD, while only 5 showed increased MD and 3
      showed decreased AD. No areas of increased FA were observed. Higher FA in
      specific periventricular white matter tracts, tending toward FA in controls, was
      associated with increased ventricular size, as well as improved clinical outcome.
      CONCLUSIONS The study shows that TBSS-based DTI is a sensitive technique for
      elucidating changes in white matter structures due to hydrocephalus and chronic
      CSF shunting and provides preliminary evidence that DTI may be a valuable tool
      for tailoring shunt procedures to monitor ventricular size following shunting and
      achieve optimal outcome, as well as for guiding the development of alternate
      therapies for hydrocephalus.

PMID- 29350599
TI  - Prognostic factors for progression in atypical meningioma.
AB  - OBJECTIVE The optimal adjuvant management for atypical meningiomas remains
      controversial. The aim of this study was to review long-term outcomes to identify
      potential prognostic factors for disease progression. METHODS From August 1992 to
      August 2013, 70 patients with atypical meningioma were treated at the authors'
      institution. Pathology revision was performed based on WHO 2007 criteria.
      Patients with multiple tumors, neurofibromatosis Type 2, or inadequate imaging
      follow-up were not eligible. The authors performed pre- and postoperative serial
      measurements of tumor volume from MRI. Age, sex, tumor location, bone
      involvement, brain invasion, mitotic figures, preoperative disease volume, extent
      of resection, tumor growth rates, use of adjuvant postoperative radiation therapy
      (PORT), and residual tumor volume at the time of radiation therapy (RT) were
      assessed by univariate and multivariate analysis to determine their potential
      impact on disease progression. RESULTS Forty patients (57%) underwent gross-total
      resection (GTR) and 30 (43%) underwent subtotal resection (STR). PORT was
      delivered to 12 patients (30%) with a GTR and in only 4 (13%) with an STR. The 5
      year progression-free survival (PFS) rate for patients in the GTR group with or
      without PORT was 100% and 54.1%, respectively (p = 0.0058). PFS for patients in
      the STR group with or without PORT was 75% and 0%, respectively (p = 0.0026). On
      multivariate analysis, STR and PORT were the only independent significant
      prognostic factors for disease progression with hazard ratios of 5.4873 (95% CI
      2.19-13.72, p = 0.0003) and 0.0464 (95% CI 0.0059-0.364, p = 0.0035),
      respectively. Based on Youden's index statistic, a cutoff residual tumor volume
      of more than 8.76 cm3 at the time of RT was associated with worse PFS (13.6% vs
      56%, p = 0.0079). Before receiving RT, the median relative and absolute growth
      rates and tumor doubling time for patients were 124.2%/year, 4.8 cm3/year, and
      1.67 years, respectively. These indices changed after RT to 0.245%/year, -0.09
      cm3/year, and -0.005 year, respectively (p < 0.05). CONCLUSIONS In atypical
      meningioma, the use of PORT is associated with improved PFS even in patients who
      undergo GTR. Patients with residual tumor volume larger than 8.76 cm3 have an
      increased risk of disease progression and should be considered for early RT.

PMID- 29350600
TI  - Long-term outcome of pallidal stimulation for Meige syndrome.
AB  - OBJECTIVE Meige syndrome is characterized by blepharospasm and varied
      subphenotypes of craniocervical dystonia. Current literature on pallidal surgery
      for Meige syndrome is limited to case reports and a few small-scale studies. The
      authors investigated the clinical outcomes of deep brain stimulation (DBS) of the
      globus pallidus internus (GPi) in patients with Meige syndrome. METHODS Sixteen
      patients who underwent GPi DBS at the Tokyo Women's Medical University Hospital
      between 2002 and 2015 were included in this study. Burke-Fahn-Marsden Dystonia
      Rating Scale (BFMDRS) movement subscale (BFMDRS-M) scores (range 0-120) obtained
      at the following 3 time points were included in this analysis: before surgery, 3
      months after surgery, and at the most recent follow-up evaluation. RESULTS The
      patients' mean age (+/- SD) at symptom onset was 46.7 +/- 10.1 years, and the
      mean disease duration at the time of the authors' initial evaluation was 5.9 +/-
      4.1 years. In 12 patients, the initial symptom was blepharospasm, and the other 4
      patients presented with cervical dystonia. The mean postoperative follow-up
      period was 66.6 +/- 40.7 months (range 13-150 months). The mean total BFMDRS-M
      scores at the 3 time points were 16.3 +/- 5.5, 5.5 +/- 5.6 (66.3% improvement, p
      < 0.001), and 6.7 +/- 7.3 (58.9% improvement, p < 0.001). CONCLUSIONS The results
      indicate long-term efficacy for GPi DBS for the majority of patients with Meige
      syndrome.

PMID- 29350601
TI  - Brain tissue Abeta42 levels are linked to shunt response in idiopathic normal
      pressure hydrocephalus.
AB  - OBJECTIVE The authors conducted a study to test if the cortical brain tissue
      levels of soluble amyloid beta (Abeta) reflect the propensity of cortical Abeta
      aggregate formation and may be an additional factor predicting surgical outcome
      following idiopathic normal pressure hydrocephalus (iNPH) treatment. METHODS
      Highly selective ELISAs (enzyme-linked immunosorbent assays) were used to
      quantify soluble Abeta40, Abeta42, and neurotoxic Abeta oligomers/protofibrils,
      associated with Abeta aggregation, in cortical biopsy samples obtained in
      patients with iNPH (n = 20), sampled during ventriculoperitoneal (VP) shunt
      surgery. Patients underwent pre- and postoperative (3-month) clinical assessment
      with a modified iNPH scale. The preoperative CSF biomarkers and the levels of
      soluble and insoluble Abeta species in cortical biopsy samples were analyzed for
      their association with a favorable outcome following the VP shunt procedure,
      defined as a >= 5-point increase in the iNPH scale. RESULTS The brain tissue
      levels of Abeta42 were negatively correlated with CSF Abeta42 (Spearman's r = 
      0.53, p < 0.05). The Abeta40, Abeta42, and Abeta oligomer/protofibril levels in
      cortical biopsy samples were higher in patients with insoluble cortical Abeta
      aggregates (p < 0.05). The preoperative CSF Abeta42 levels were similar in
      patients responding (n = 11) and not responding (n = 9) to VP shunt treatment at
      3 months postsurgery. In contrast, the presence of cortical Abeta aggregates and
      high brain tissue Abeta42 levels were associated with a poor outcome following VP
      shunt treatment (p < 0.05). CONCLUSIONS Brain tissue measurements of soluble
      Abeta species are feasible. Since high Abeta42 levels in cortical biopsy samples
      obtained in patients with iNPH indicated a poor surgical outcome, tissue levels
      of Abeta species may be associated with the clinical response to shunt treatment.

PMID- 29350602
TI  - A novel approach to 32-channel peripheral nervous system myelin imaging in vivo,
      with single axon resolution.
AB  - OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the
      rat peripheral nervous system (PNS) has not been well described. Here, the
      authors have developed a highly stable platform for performing imaging of the
      tibial nerve in live rodents, thus allowing the capture of high-resolution, high
      magnification spectral images requiring long acquisition times. By further
      exploiting the qualities of the topically applied myelin dye Nile red, this
      technique is capable of visualizing the detailed microenvironment of peripheral
      nerve demyelination injury and recovery, while allowing us to obtain images of
      exogenous Schwann cell myelination in a living animal. METHODS The authors caused
      doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP
      rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs
      to the zone of injury. Prior to acquiring images of myelin recovery in these
      nerves, a tibial nerve window was constructed using a silicone hemitube, a fast
      drying silicone polymer, and a small coverslip. This construct was then affixed
      to a 3D-printed nerve stage, which in turn was affixed to an external
      fixation/microscope stage device. Myelin visualization was facilitated by the
      topical application of Nile red. RESULTS The authors reliably demonstrated
      intravital peripheral nerve myelin imaging with micron-level resolution and
      magnification, and minimal movement artifact. The detailed microenvironment of
      nerve remyelination can be vividly observed, while exogenously applied Schwann
      cells and skin-derived precursor Schwann cells can be seen myelinating axons.
      CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the
      living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable
      intravital peripheral nerve imaging, making possible high-definition spectral
      imaging with long acquisition times.

PMID- 29350603
TI  - Decision tree analysis in subarachnoid hemorrhage: prediction of outcome
      parameters during the course of aneurysmal subarachnoid hemorrhage using decision
      tree analysis.
AB  - OBJECTIVE The aim of this study was to create prediction models for outcome
      parameters by decision tree analysis based on clinical and laboratory data in
      patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS The database
      consisted of clinical and laboratory parameters of 548 patients with aSAH who
      were admitted to the Neurocritical Care Unit, University Hospital Zurich. To
      examine the model performance, the cohort was randomly divided into a derivation
      cohort (60% [n = 329]; training data set) and a validation cohort (40% [n = 219];
      test data set). The classification and regression tree prediction algorithm was
      applied to predict death, functional outcome, and ventriculoperitoneal (VP) shunt
      dependency. Chi-square automatic interaction detection was applied to predict
      delayed cerebral infarction on days 1, 3, and 7. RESULTS The overall mortality
      was 18.4%. The accuracy of the decision tree models was good for survival on day
      1 and favorable functional outcome at all time points, with a difference between
      the training and test data sets of < 5%. Prediction accuracy for survival on day
      1 was 75.2%. The most important differentiating factor was the interleukin-6 (IL
      6) level on day 1. Favorable functional outcome, defined as Glasgow Outcome Scale
      scores of 4 and 5, was observed in 68.6% of patients. Favorable functional
      outcome at all time points had a prediction accuracy of 71.1% in the training
      data set, with procalcitonin on day 1 being the most important differentiating
      factor at all time points. A total of 148 patients (27%) developed VP shunt
      dependency. The most important differentiating factor was hyperglycemia on
      admission. CONCLUSIONS The multiple variable analysis capability of decision
      trees enables exploration of dependent variables in the context of multiple
      changing influences over the course of an illness. The decision tree currently
      generated increases awareness of the early systemic stress response, which is
      seemingly pertinent for prognostication.

PMID- 29350604
TI  - Letter to the Editor. Is preoperative hypoalbuminemia really a risk factor
      associated with acute kidney injury and mortality after brain tumor surgery?

PMID- 29350605
TI  - In situ administration of abciximab for thrombus resolution during intracranial
      bypass surgery: case report.
AB  - Abciximab is a glycoprotein IIb/IIIa receptor antagonist that functions to
      prevent platelet aggregation, thus reducing thrombus initiation and propagation.
      It has been widely used during percutaneous endovascular interventions, such as
      aneurysm coil embolization, angioplasty, atherectomy, and stent placement, as
      both a preventative and a salvage therapy. The use of abciximab in cardiac and
      neurosurgical procedures has been associated with a reduced incidence of ischemic
      complications and a decreased need for repeated intervention. In these settings,
      abciximab has been delivered transarterially via a microcatheter or infused
      intravenously for systemic administration. The authors describe novel in situ
      delivery of abciximab as an agent to dissolve "white clots," which are composed
      primarily of platelets, during an intracranial superficial temporal artery to
      middle cerebral artery bypass in a 28-year-old woman with severe intracranial
      occlusive disease. Abciximab was able to resolve multiple platelet-based clots
      after unsuccessful attempts with conventional clot dispersal techniques, such as
      heparinized saline, tissue plasminogen activator, mechanical passage of a wire
      through the vessel lumen, and multiple takedowns and re-anastomosis. After
      abciximab was administered, patency was demonstrated intraoperatively using
      indocyanine green dye and confirmed postoperatively at 1 and 10 months via CT
      angiography. The in situ use of abciximab as an agent to disperse a thrombus
      during intracranial bypass surgery is novel and has not previously been described
      in the literature, and serves as an additional tool during intracranial vessel
      bypass surgery.

PMID- 29350607
TI  - Shaping the future of science publishing: The evolution of metrics.

PMID- 29350608
TI  - Acute transverse myelitis following scrub typhus: A case report and review of the
      literature.
AB  - Context Scrub typhus is an acute febrile disease caused by Orientia
      tsutsugamushi. The disease can usually involve the lungs, heart, liver, spleen
      and brain through hematogenous dissemination. However, very rarely, acute
      transverse myelitis in the spinal cord develops from scrub typhus. We present a
      case of acute transverse myelitis following scrub typhus with a review of the
      literature. Findings A 66-year-old male visited a hospital for general myalgia,
      mild headache, and fever in October. He was noted to have thick, black papule
      skin on his abdomen, which was highly suggestive of scrub typhus. To confirm the
      diagnosis, O. tsutsugamushi antibody titers were examined and detected highly in
      serum by an indirect fluorescence antibody assay. Doxycycline, the standard
      treatment for scrub typhus, was administered. However, after seven days of
      treatment, he rapidly developed weakness in the right leg, paresthesia in both
      lower limbs, and voiding difficulty. Spinal magnetic resonance imaging (MRI)
      revealed lesions with high signal intensity involving the spinal cord at the
      thoracolumbar junction. Paraparesis gradually improved following steroid pulse
      therapy for five days. At one-year follow-up, he could walk without cane.
      Conclusions Orientia tsutsugamushi causes scrub typhus, which can affect not only
      the brain, but also the spinal cord. Although acute transverse myelitis develops
      rarely from scrub typhus, this should be considered as differential diagnosis in
      patients of fever with neurological deficit in endemic areas.

PMID- 29350610
TI  - Research edition.

PMID- 29350609
TI  - Addressing food wastage in the framework of the UN Sustainable Development Goals.

PMID- 29350611
TI  - To Do No Harm: Humanitarian Aid in Conflict Demands Political Engagement.
AB  - Humanitarian aid in settings of conflict has always been fraught with challenges.
      In the absence of political engagement, however, manipulation by state
      authorities, however, have the potential to pervert aid intervention to inflict
      harm. South Sudan exemplifies how states may abuse the humanitarian response to
      retreat from public responsibility, divert funds to further violence and conflict
      and dictate the distribution of aid. Recent trends toward nationalist policies in
      the West that favor disengagement and limited military strikes have the very
      effect of allowing this abuse to transform humanitarian aid into a tool for harm.
      (Disaster Med Public Health Preparedness. 2018;12:567-568).

PMID- 29350612
TI  - The Effects of Betaine on the Nuclear Fractal Dimension, Chromatin Texture, and
      Proliferative Activity in Hepatocytes in Mouse Model of Nonalcoholic Fatty Liver
      Disease.
AB  - The effects of betaine on hepatocytes chromatin architecture changes were
      examined by using fractal and gray-level co-occurrence matrix (GLCM) analysis in
      methionine/choline-deficient (MCD) diet-induced, nonalcoholic fatty liver disease
      (NAFLD). Male C57BL/6 mice were divided into groups: (1) Control: standard diet;
      (2) BET: standard diet and betaine supplementation through drinking water
      (solution 1.5%); (3) MCD group: MCD diet for 6 weeks; (4) MCD+BET: fed with MCD
      diet + betaine for 6 weeks. Liver tissue was collected for histopathology,
      immunohistochemistry, and determination of fractal dimension and GLCM parameters.
      MCD diet induced diffuse micro- and macrovesicular steatosis accompanied with
      increased Ki67-positive hepatocyte nuclei. Steatosis and Ki67 immunopositivity
      were less prominent in the MCD+BET group compared with the MCD group. Angular
      second moment (ASM) and inverse difference moment (IDM) (textural homogeneity
      markers) were significantly increased in the MCD+BET group versus the MCD group
      (p<0.001), even though no difference between the MCD and the control group was
      evident. Heterogeneity parameters, contrast, and correlation were significantly
      increased in the MCD group versus the control (p<0.001). On the other hand,
      betaine treatment significantly reduced correlation, contrast, and entropy
      compared with the MCD group (p<0.001). Betaine attenuated MCD diet-induced NAFLD
      by reducing fat accumulation and inhibiting hepatocyte proliferation. Betaine
      supplementation increased nuclear homogeneity and chromatin complexity with
      reduction of entropy, contrast, and correlation.

PMID- 29350613
TI  - FGF mediated MAPK and PI3K/Akt Signals make distinct contributions to
      pluripotency and the establishment of Neural Crest.
AB  - Early vertebrate embryos possess cells with the potential to generate all
      embryonic cell types. While this pluripotency is progressively lost as cells
      become lineage restricted, Neural Crest cells retain broad developmental
      potential. Here, we provide novel insights into signals essential for both
      pluripotency and neural crest formation in Xenopus. We show that FGF signaling
      controls a subset of genes expressed by pluripotent blastula cells, and find a
      striking switch in the signaling cascades activated by FGF signaling as cells
      lose pluripotency and commence lineage restriction. Pluripotent cells display and
      require Map Kinase signaling, whereas PI3 Kinase/Akt signals increase as
      developmental potential is restricted, and are required for transit to certain
      lineage restricted states. Importantly, retaining a high Map Kinase/low Akt
      signaling profile is essential for establishing Neural Crest stem cells. These
      findings shed important light on the signal-mediated control of pluripotency and
      the molecular mechanisms governing genesis of Neural Crest.

PMID- 29350614
TI  - LIPG signaling promotes tumor initiation and metastasis of human basal-like
      triple-negative breast cancer.
AB  - Current understanding of aggressive human basal-like triple-negative breast
      cancer (TNBC) remains incomplete. In this study, we show endothelial lipase
      (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG
      is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG
      possesses a lipase-dependent function that supports cancer cell proliferation and
      a lipase-independent function that promotes invasiveness, stemness and
      basal/epithelial-mesenchymal transition features of TNBC. Mechanistically, LIPG
      executes its oncogenic function through its involvement in interferon-related
      DTX3L-ISG15 signaling, which regulates protein function and stability by
      ISGylation. We show that DTX3L, an E3-ubiquitin ligase, is required for
      maintaining LIPG protein levels in TNBC cells by inhibiting proteasome-mediated
      LIPG degradation. Inactivation of LIPG impairs DTX3L-ISG15 signaling, indicating
      the existence of DTX3L-LIPG-ISG15 signaling. We further reveal LIPG-ISG15
      signaling is lipase-independent. We demonstrate that DTX3L-LIPG-ISG15 signaling
      is essential for malignancies of TNBC cells. Targeting this pathway provides a
      novel strategy for basal-like TNBC therapy.

PMID- 29350615
TI  - Chimeras could help in the fight against leptospirosis.
AB  - Understanding the structure of an antigen can guide the design of improved
      antigen-based vaccines.

PMID- 29350617
TI  - Adolescents and e-cigarettes: Objects of concern may appear larger than they are.

PMID- 29350616
TI  - A disassembly-driven mechanism explains F-actin-mediated chromosome transport in
      starfish oocytes.
AB  - While contraction of sarcomeric actomyosin assemblies is well understood, this is
      not the case for disordered networks of actin filaments (F-actin) driving diverse
      essential processes in animal cells. For example, at the onset of meiosis in
      starfish oocytes a contractile F-actin network forms in the nuclear region
      transporting embedded chromosomes to the assembling microtubule spindle. Here, we
      addressed the mechanism driving contraction of this 3D disordered F-actin network
      by comparing quantitative observations to computational models. We analyzed 3D
      chromosome trajectories and imaged filament dynamics to monitor network behavior
      under various physical and chemical perturbations. We found no evidence of myosin
      activity driving network contractility. Instead, our observations are well
      explained by models based on a disassembly-driven contractile mechanism. We
      reconstitute this disassembly-based contractile system in silico revealing a
      simple architecture that robustly drives chromosome transport to prevent
      aneuploidy in the large oocyte, a prerequisite for normal embryonic development.

PMID- 29350619
TI  - Growth and lattice dynamics of ultrathin BaO films on Pt(0 0 1).
AB  - We report on the surface phonons of long-range ordered BaO thin films grown on
      Pt(0 0 1). In the thickness range between 4 and 28 ML, we find unstrained BaO(0 0
      1)-([Formula: see text]) bulk-like terminated films which coincide with a Pt(0 0
      1)-c([Formula: see text]) lattice periodicity. The dipole-active lattice
      vibrations were determined using high-resolution electron energy loss
      spectroscopy. For all BaO film thicknesses, a single Fuchs-Kliewer phonon
      polariton is observed. Its intensity increases and its frequency softens with
      increasing film thickness. These thickness-dependent properties and the spectral
      shape are quantitatively discussed on the basis of dielectric theory, where a
      proper modeling requires three components: the dielectric response of the BaO
      film itself, the plasmonic response of the metallic substrate, and a weak damping
      due to a defect-induced doping within the oxide film. For a full description,
      also the quantization of the phonon wavevector due to the confinement within the
      film of finite thickness has to be taken into account.

PMID- 29350620
TI  - Trions in bulk and monolayer materials: Faddeev equations and hyperspherical
      harmonics.
AB  - The negatively T - and positively T + charged trions in bulk and monolayer
      semiconductors are studied in the effective mass approximation within the
      framework of a potential model. The binding energies of trions in various
      semiconductors are calculated by employing the Faddeev equation with the Coulomb
      potential in 3D configuration space. Results of calculations of the binding
      energies for T - are consistent with previous computational studies, while the T
      + is unbound for all considered cases. The binding energies of trions in
      monolayer semiconductors are calculated using the method of hyperspherical
      harmonics by employing the Keldysh potential. It is shown that 2D T - and T +
      trions are bound and the binding energy of the positive trion is always greater
      than for the negative trion due to the heavier effective mass of holes. Our
      calculations demonstrate that screening effects play an important role in the
      formation of bound states of trions in 2D semiconductors.

PMID- 29350618
TI  - A call to end the epidemic of adolescent E-cigarette use.

PMID- 29350621
TI  - Electrodeposited binder-free NiCo2O4@carbon nanofiber as a high performance anode
      for lithium ion batteries.
AB  - Binder-free nickel cobaltite on a carbon nanofiber (NiCo2O4@CNF) anode for
      lithium ion batteries was prepared via a two-step procedure of electrospinning
      and electrodeposition. The CNF was obtained by annealing electrospun poly
      acrylonitrile (PAN) in nitrogen (N2). The NiCo2O4 nanostructures were then grown
      on the CNF by electrodeposition, followed by annealing in air. Experimental
      results showed that vertically aligned NiCo2O4 nanosheets had uniformly grown on
      the surface of the CNF, forming an interconnected network. The NiCo2O4@CNF
      possessed considerable lithium storage capacity and cycling stability. It
      exhibited a high reversible capacity of 778 mAhg-1 after 300 cycles at a current
      density of 0.25 C (1 C = 890 mAg-1) with an average capacity loss rate of 0.05%
      per cycle. The NiCo2O4@CNF had considerable rate capacities, delivering a
      capacity of 350 mAhg-1 at a current density of 2.0 C. The outstanding
      electrochemical performance can be mainly attributed to the following: (1) The
      nanoscale structure of NiCo2O4 could not only shorten the diffusion path of
      lithium ions and electrons but also increase the specific surface area, providing
      more active sites for electrochemical reactions. (2) The CNF with considerable
      mechanical strength and electrical conductivity could function as an anchor for
      the NiCo2O4 nanostructure and ensure an efficient electron transfer. (3) The
      porous structure resulted in a high specific surface area and an effective buffer
      for the volume changes during the repeated charge-discharge processes. Compared
      with a conventional hydrothermal method, electrodeposition could significantly
      simplify the preparation of NiCo2O4, with a shorter preparation period and lower
      energy consumption. This work provides an alternative strategy to obtain a high
      performance anode for lithium ion batteries.

PMID- 29350622
TI  - Beyond HRV: attractor reconstruction using the entire cardiovascular waveform
      data for novel feature extraction.
AB  - : Advances in monitoring technology allow blood pressure waveforms to be
      collected at sampling frequencies of 250-1000 Hz for long time periods. However,
      much of the raw data are under-analysed. Heart rate variability (HRV) methods, in
      which beat-to-beat interval lengths are extracted and analysed, have been
      extensively studied. However, this approach discards the majority of the raw
      data. OBJECTIVE: Our aim is to detect changes in the shape of the waveform in
      long streams of blood pressure data. APPROACH: Our approach involves extracting
      key features from large complex data sets by generating a reconstructed attractor
      in a three-dimensional phase space using delay coordinates from a window of the
      entire raw waveform data. The naturally occurring baseline variation is removed
      by projecting the attractor onto a plane from which new quantitative measures are
      obtained. The time window is moved through the data to give a collection of
      signals which relate to various aspects of the waveform shape. MAIN RESULTS: This
      approach enables visualisation and quantification of changes in the waveform
      shape and has been applied to blood pressure data collected from conscious
      unrestrained mice and to human blood pressure data. The interpretation of the
      attractor measures is aided by the analysis of simple artificial waveforms.
      SIGNIFICANCE: We have developed and analysed a new method for analysing blood
      pressure data that uses all of the waveform data and hence can detect changes in
      the waveform shape that HRV methods cannot, which is confirmed with an example,
      and hence our method goes 'beyond HRV'.

PMID- 29350623
TI  - Exploring the role of genome and structural ions in preventing viral capsid
      collapse during dehydration.
AB  - Even though viruses evolve mainly in liquid milieu, their horizontal transmission
      routes often include episodes of dry environment. Along their life cycle, some
      insect viruses, such as viruses from the Dicistroviridae family, withstand
      dehydrated conditions with presently unknown consequences to their structural
      stability. Here, we use atomic force microscopy to monitor the structural changes
      of viral particles of Triatoma virus (TrV) after desiccation. Our results
      demonstrate that TrV capsids preserve their genome inside, conserving their
      height after exposure to dehydrating conditions, which is in stark contrast with
      other viruses that expel their genome when desiccated. Moreover, empty capsids
      (without genome) resulted in collapsed particles after desiccation. We also
      explored the role of structural ions in the dehydration process of the virions
      (capsid containing genome) by chelating the accessible cations from the external
      solvent milieu. We observed that ion suppression helps to keep the virus height
      upon desiccation. Our results show that under drying conditions, the genome of
      TrV prevents the capsid from collapsing during dehydration, while the structural
      ions are responsible for promoting solvent exchange through the virion wall.

PMID- 29350624
TI  - Conductive bridge random access memory characteristics of SiCN based transparent
      device due to indium diffusion.
AB  - In this work, the transparent bipolar resistive switching characteristics of a
      SiCN-based ITO/SiCN/AZO structure due to In diffusion from ITO is studied. The
      SiCN based device is found to be 80% transparent in the visible wavelength
      region. This device, with AZO as both top and bottom electrodes, does not show
      any RRAM property due to deposition of the high quality O2-free SiCN film.
      Replacing the AZO top electrode with ITO in this device results in good resistive
      switching (RS) characteristics with a high on/off ratio and long retention.
      Replacing the SiCN film with ZrO2 also results in excellent RS characteristics
      due to the formation of an oxygen vacancies filament inside the ZrO2 film. A
      resistance ratio of on/off is found to be higher in the SiCN based device
      compared to that of the ZrO2 device. Diffusion of In from ITO into the SiCN film
      on application of high positive voltage during forming can be attributed to the
      occurrence of RS in the device, which is confirmed by the analyses of energy
      dispersive spectroscopy and secondary-ion mass spectrometry. This study shows a
      pathway for the fabrication of CBRAM based transparent devices for non-volatile
      memory application.

PMID- 29350625
TI  - Dynamically tunable interface states in 1D graphene-embedded photonic crystal
      heterostructure.
AB  - Optical interface states exhibit promising applications in nonlinear photonics,
      low-threshold lasing, and surface-wave assisted sensing. However, the further
      application of interface states in configurable optics is hindered by their
      limited tunability. Here, we demonstrate a new approach to generate dynamically
      tunable and angle-resolved interface states using graphene-embedded photonic
      crystal (GPC) heterostructure device. By combining the GPC structure design with
      in situ electric doping of graphene, a continuously tunable interface state can
      be obtained and its tuning range is as wide as the full bandgap. Moreover, the
      exhibited tunable interface states offer a possibility to study the
      correspondence between space and time characteristics of light, which is beyond
      normal incident conditions. Our strategy provides a new way to design
      configurable devices with tunable optical states for various advanced optical
      applications such as beam splitter and dynamically tunable laser.

PMID- 29350626
TI  - High mobility In<sub>0.75</sub>Ga<sub>0.25</sub>As quantum wells in an InAs
      phonon lattice.
AB  - InGaAs based devices are great complements to silicon for CMOS, as they provide
      an increased carrier saturation velocity, lower operating voltage and reduced
      power dissipation. In this work we show that&#13; In0.75Ga0.25As quantum wells
      with a high mobility, 15 000 to 20 000 cm2/V.s at ambient temperature, show&#13;
      an InAs-like phonon with an energy of 28.8 meV, frequency of 232 cm-1 that
      dominates the polar-optical mode scattering from ~&#13; 70 K to 300 K. The
      optical phonon frequency is insensitive to the carrier density modulated with a
      surface&#13; gate or LED illumination. We model the electron scattering
      mechanisms as a function of temperature and&#13; identify mechanisms that limit
      the electron mobility in In0.75Ga0.25As quantum wells. Background impurity&#13;
      scattering starts to dominate for temperatures <100 K. In the high mobility
      In0.75Ga0.25As quantum well,&#13; GaAs-like phonons do not couple to the electron
      gas unlike the case of In0.53Ga0.47As quantum wells.

PMID- 29350627
TI  - Franck Condon shift assessment in 2D MoS<sub>2</sub>.
AB  - Optical spectroscopy (OS) techniques are often coupled with first-principles
      density functional theoretical (DFT) calculations for determining the precise
      influence of defects on the electronic and structural properties of two
      dimensional (2D) TMDs. Such calculations are carried out presuming there is
      little or no effect of vibrational transitions on the observed electronic
      spectrum. However, if the effect of change in vibrational energy [Franck Condon
      (FC) shift] associated with such a transition is large, it could possibly lead to
      a different origin for the observed peak. One such instance is the attribution of
      the 0.75 eV cathodoluminescence peak by Fabbri et. al. [Nat. Commun. 7, 13044
      (2016)]. to an optical transition from an S vacancy level in the band gap, under
      the assumption that the FC shift is negligible. Here, by first principles
      constrained DFT calculations using hybrid HSE06 functional we show that this
      combined prediction of OS and DFT calculations is valid for 2D MoS2 since the FC
      shift associated with electronic transitions from a sulfur vacancy is, indeed,
      small ~28 meV. Based on our calculations we conclude that it is reasonable to
      make a direct connection between DFT calculations and optical spectroscopy
      techniques in this material, hence, establishing a one to one relation between
      defect related emission bands and electronic transitions from the defect levels.

PMID- 29350628
TI  - Inkjet printing and electrical characterisation of DNA - templated cadmium
      sulfide nanowires.
AB  - Cadmium sulfide can be templated on ?-DNA molecules to form an aqueous dispersion
      of CdS/?-DNA nanowires. Subsequent addition of ethylene glycol to 50% v/v is
      sufficient to formulate an ink suitable for printing using piezoelectric drop-on
      demand technology. Printed droplet arrays show a coffee-ring morphology of
      individual deposits by fluorescence and Raman microscopy, but upon increasing the
      number of layers of printed material by repeated printing over each droplet, the
      dry deposit approaches closer to a disc shape. It is also possible to print
      parallel tracks by reducing the droplet separation in the array until
      neighbouring droplets overlap before they dry. The droplets coalesce to form a
      strip of width roughly equal to the diameter of the droplets. Evaporation-driven
      capillary flow sends the nanowires to the edges of the strip and when dry they
      form parallel tracks of CdS/?-DNA nanowire bundles. Both droplets and tracks were
      printed onto Pt-on-glass interdigitated microelectrodes (10 ?m width, 10 ?m gap).
      The current-voltage characteristics of these two-terminal devices were
      approximately ohmic, but with some hysteresis. The conductance increased with
      temperature as a simple activated process with activation energies of 0.57 +/-
      0.02 eV (tracks) and 0.39 +/- 0.02 eV (droplets). The impedance spectra of the
      printed films were consistent with hopping between CdS grains.

PMID- 29350629
TI  - Conductive films of silver nanoparticles as novel susceptors for induction
      welding of thermoplastic composites.
AB  - In the present work, a conductive film of silver nanoparticles (nAg) as a novel
      heating element type, called susceptor, was developed and tested for induction
      welding of carbon fiber/polyphenylene sulfide (CF/PPS) thermoplastic composites,
      i.e., unidirectional pre-impregnated 16 plies of CF/PPS compression-molded in a
      quasi-isotropic stacking sequence. The nAg were synthesized, dispersed in
      deionized (DI) water and casted onto a pure PPS film, resulting in a conductive
      film upon the evaporation of DI water and thermal post-annealing. The thermal
      annealing at 250  degrees C significantly (by 7 orders) decreased the film's
      electrical resistivity from 9.4 * 103 down to 3.1 * 10-4 Omega cm. The new
      susceptors led to fast heating rates in induction welding when compared to the
      standard stainless steel mesh susceptors under similar welding conditions. Lap
      shear mechanical testing revealed that the apparent lap shear strength (LSS) is
      sensitive to the susceptors' resistivity and the input current. A relatively high
      LSS value was achieved for the specimens welded using the new susceptors which
      exceeded the value of those welded using stainless steel mesh susceptors (28.3
      MPa compared to 20 MPa). The weld interface and specimens' cross-section
      observation revealed that the nAg were dispersed and embedded into the resin upon
      welding. This study contains preliminary results that show high potential of
      nanoparticles as effective susceptors to further improve the mechanical
      performance of the joints in welding of thermoplastic composites.

PMID- 29350630
TI  - GaAs quantum dots in a GaP nanowire photodetector.
AB  - We report the structural, optical and electrical properties of GaAs quantum dots
      (QDs) embedded along GaP nanowires. The GaP nanowires contained p-i-n junctions
      with 15 consecutively grown GaAs QDs within the intrinsic region. The nanowires
      were grown by molecular beam epitaxy using the self-assisted vapor-liquid-solid
      process. The crystal structure of the NWs alternated between twinned ZB and WZ as
      the composition along the NW alternated between the GaP barriers and the GaAs
      QDs, respectively, leading to a polytypic structure with a periodic modulation of
      the NW sidewall facets. Photodetector devices containing QDs showed absorption
      beyond the bandgap of GaP in comparison to nanowires without QDs. Voltage
      dependent measurements suggested a field emission process of carriers from the
      QDs.

PMID- 29350631
TI  - Competition and coexistence of polar and non-polar states in Sr1-x Ca x TiO3: an
      investigation using pressure dependent Raman spectroscopy.
AB  - The competition and cooperation between ferroelectric and anti-ferro-distortion
      (AFD) instabilities are studied using pressure dependent Raman spectroscopy on
      polycrystalline powder samples of Sr1-x Ca x TiO3(x  =  0.0, 0.06, 0.25, 0.35).
      For x  =  0.0 composition, a broad polar mode is detected in the Raman spectra
      above 6 GPa, while for x  =  0.06 composition, the polar modes appear well above
      9 GPa where the AFD modes showed strong suppression. In x  =  0.25 and 0.35
      composition, the application of small pressure resulted in the appearance of
      strong AFD modes suppressing the polar modes. At elevated pressures, re-entrant
      polar modes are observed along with the broad AFD modes and some new peaks are
      also observed, signifying the lowering of local symmetry. The reappearance of
      polar modes is found to be related to pressure induced symmetry disorder at local
      level, suggesting its electronic origin. The re-entrant polar modes observed at
      higher pressure values are found to be significantly broad and asymmetric in
      nature, signifying the development of ferroelectric micro regions/nano domains
      coexisting with AFD. The lower symmetry at local length scale provides a
      conducive atmosphere for coexisting AFD and FE instabilities.

PMID- 29350632
TI  - Defect-selective dry etching for quick and easy probing of hexagonal boron
      nitride domains.
AB  - In this study, we demonstrate a new method to selectively etch the point defects
      or the boundaries of as-grown hexagonal boron nitride (hBN) films and flakes in
      situ on copper substrates using hydrogen and argon gases. The initial quality of
      the chemical vapor deposition-grown hBN films and flakes was confirmed by UV-vis
      absorption spectroscopy, atomic force microscopy, and transmission electron
      microscopy. Different gas flow ratios of Ar/H2 were then employed to etch the
      same quality of samples and it was found that etching with hydrogen starts from
      the point defects and grows epitaxially, which helps in confirming crystalline
      orientations. However, etching with argon is sensitive to line defects
      (boundaries) and helps in visualizing the domain size. Finally, based on this
      defect-selective dry etching technique, it could be visualized that the domains
      of a polycrystalline hBN monolayer merged together with many parts, even with
      those that grew from a single nucleation seed.

PMID- 29350633
TI  - Diagnostic imaging and intervention of the musculoskeletal system: state of the
      art.
AB  - The study of the musculoskeletal system has always been one of the most important
      application for diagnostic imaging in radiology (1-4).

PMID- 29350634
TI  - MRI of popliteo-meniscal fasciculi of the knee: a pictorial review.
AB  - The popliteomeniscal fascicules (PMFs) provide the attachment of the lateral
      meniscus to the popliteus musculotendinous region, forming the floor and the roof
      the popliteal hiatus. In the second half of 1900's, some anatomic studies claim
      the important function of the PMF as stabilizers of the lateral meniscus; these
      anatomical structures work in conjunction with the popliteus musculotendinous
      unit to prevent excessive lateral meniscal movement and possible meniscus
      subluxation. A correct diagnosis of the PMFs pathology is crucial to establish
      the suitable surgical treatment for each patient. MRI is a well-established
      imaging technique in the musculoskeletal system and the frequency of recognition
      of normal PMF in the normal knees is high in almost all MRI studies. At day, the
      gold standard for diagnosis is the arthroscopic evaluation that allows the direct
      visualization of the popliteo-meniscal ligaments at popliteal hiatus and
      evaluation of lateral meniscal movements. For this reason if unstable condition
      of meniscus was suspected, arthroscopic observation with probing into the
      popliteo-meniscal fascicle area is essential for the identification of the
      fascicle tears. Despite many treatments have being proposed in literature since
      now there is high recurrence of knee locking after repair and it is fundamental
      to develop new surgical techniques in order to achieve better outcome.

PMID- 29350635
TI  - Magnetic Resonance Imaging correlates of benign and malignant alterations of the
      spinal bone marrow.
AB  - BACKGROUND AND AIM OF THE WORK: Bone marrow (BM) abnormalities in the spine are a
      common, sometimes unexpected, finding on Magnetic Resonance Imaging (MRI), which
      is the most sensitive imaging modality to evaluate the marrow, and their
      interpretation can be difficult for the unexperienced radiologist. In this
      review, the MRI appearance of normal age-related BM changes, as well as the
      imaging features of benign and malignant diseases, are presented. DISCUSSION: A
      large variety of BM signal alterations has been identified and described,
      including normal variants, BM reconversion,  degenerative changes, infections,
      spondyloarthritis and osteonecrosis, trauma, neoplastic lesions (both primary or
      metastatic), post-radiation and chemotherapy sequelae. CONCLUSIONS: Knowledge of
      normal age-related BM appearance, normal variants and patterns of involvement in
      focal and diffuse bone diseases is essential, together with clinical and
      laboratory data, to narrow the list of the possible differential diagnoses. The
      radiologist should be familiar with these signal changes, as they can sometimes
      be discovered incidentally. In this context, it is equally important not to
      attribute pathological significance to benign alterations and to promptly detect
      signs of malignant diseases.

PMID- 29350636
TI  - Imaging of pediatric foot disorders.
AB  - Infants and children undergo imaging studies to evaluate a wide variety of
      congenital and acquired disorders. Imaging protocols have to consider the
      patient's comfort, level of anxiety, and smaller size. The first imaging study is
      usually made with plain radiographs. The routine radiographic examination of the
      foot includes the anteroposterior (AP), lateral, and oblique projections.
      Magnetic Resonance Imaging (RMI) provides excellent anatomic detail of cartilage,
      vasculature and soft tissue thanks to superior soft tissue contrast and spatial
      resolution, so is valuable in many cases. According to the clinical and objective
      signs, guided by the radiographs images, we can be oriented to perform Computed
      Tomography (CT), CT imaging or MRI imaging. CT imaging is useful to observe the
      bones but it has the disadvantage of using radiation and doesn't  adequately
      define the bone's non-ossified portions. On the contrary, MRI imaging is very
      useful in identifying the cartilaginous parts and vascular and soft tissues,
      thanks to its superior contrast and spatial resolution. Finally, it is important
      to orientate the diagnostic process keeping in mind the clinical sign of the
      patient and to use the most appropriate diagnostic technique.

PMID- 29350637
TI  - Clinical utility of eco-color-power Doppler ultrasonography and contrast enhanced
      magnetic resonance imaging for interpretation and quantification of joint
      synovitis: a review.
AB  - With the introduction of new biologics such as anti-TNF-alpha antibodies and
      other therapies in the treatment of inflammatory arthritis, capable of halting
      joint destruction and functional disability, there are new pressures on
      diagnostic and prognostic imaging. Early demonstration of pre-erosive
      inflammatory features and monitoring of the long-term effects of treatment are
      becoming increasingly important. Early detection of synovitis offers advantages
      in terms of allowing early instigation of therapy and may allow the
      identification of those patients displaying more aggressive disease who might
      benefit from early intervention with expensive DMARD therapy. Advanced imaging
      techniques such as ultrasound (US) and magnetic resonance imaging (MRI) have
      focussed on the demonstration and quantification of synovitis and allow early
      diagnosis of inflammatory arthropathies such as rheumatoid arthritis (RA) and
      psoriatic arthritis (PsA). Synovitis represents a potential surrogate measure of
      disease activity that can be monitored using either MRI or US; the techniques
      have, generally, focused on monitoring synovial volume or quality as assessed by
      its vascularity. However to achieve these goals, standardisation and validation
      of US and MRI are required to ensure accurate diagnosis, reproducibility and
      reliability. Each modality has different strengths and weaknesses and levels of
      validation. This article aims to increase the awareness of radiologists and
      rheumatologists about this field and to encourage them to participate and
      contribute to the ongoing development of these modalities. Without this
      collaboration, it is unlikely that these modalities will reach their full
      potential in the field of rheumatological imaging. This review is in two parts.
      The first part addresses the role of US and colour or power Doppler sonography
      (PDUS) in the detection and monitoring of synovitis in inflammatory
      arthropathies. The second part will look at advanced MR imaging and Dynamic
      contrast-enhanced MRI techniques and in particular how they are applied to the
      monitoring of the disease process.

PMID- 29350638
TI  - Weight-bearing MRI of the knee: a review of advantages and limits.
AB  - Standard knee imaging with MRI is usually performed with patient in recumbent
      position under non-weight-bearing conditions. Recently, magnetic resonance
      imaging systems to scan the knee joint under weight bearing conditions has been
      proposed as an approach to improve the clinical utility of musculoskeletal MRI.
      Imaging under loading can be useful to understand the natural motion behavior of
      the knee joint and to identify conditions that are challenging to diagnose by
      using standard position. We reviewed the literature on weight-bearing MR imaging
      of the knee to describe the current state of use of such MRI technologies,
      evaluating the advantages and the potential limitations of these technologies.

PMID- 29350639
TI  - Dynamic MRI in the evaluation of the spine: state of the art.
AB  - INTRODUCTION: Degenerative disease of the spine is a generic term encompassing a
      wide range of different disease processes, which leads to spinal instability;
      traumatic/neoplastic events can accelerate this aging process. Therefore, the
      dynamic nature of the spine and its mobility across multiple segments is
      difficult to depict with any single imaging modality. METHODS: A review of PubMed
      databases for articles published about kMRI in patients with cervical and lumbar
      spinal desease was performed. We focused on the physiopathological changes in the
      transition from supine to upright position in spine instability. DISCUSSION:
      Until a few years ago, X-ray was the only imaging modality for the spine in the
      upright position. Of the imaging techniques currently available, MRI provides the
      greatest range of information and the most accurate delineation of soft-tissue
      and osseous structures. Conventional MRI examinations of the spine usually are
      performed in supine position, in functional rest, but the lumbar spine
      instability is often shown only by upright standing. This can result in negative
      findings, even in the presence of symptoms. Regardless, the final result is
      distorted. To overcome this limitation, Kinetic MRI (kMRI) can image patients in
      a weight-bearing position and in flexed and extended positions, thus revealing
      abnormalities that are missed by traditional MRI studies. CONCLUSION: Despite
      some limitations, the upright MRI can be a complementary investigation to the
      traditional methods when there are negative results in conventional MRI in
      symptomatic patients or when surgical therapy is scheduled.

PMID- 29350640
TI  - Scapular fractures: a common diagnostic pitfall.
AB  - Scapular fractures are one of the most difficult fractures to diagnose on
      radiographs. Detection can be challenging because of the obscuration by the
      overlying structures or incomplete imaging due to difficult patient
      collaboration. Familiarity with imaging characteristics of these abnormalities
      will allow radiologists to better diagnose and characterize scapular fractures.
      Three-dimensional computed tomographic scans are considered the gold standard for
      scapular diagnoses. Treatment strategies differ depending on the type of scapular
      fractures, but the site and degree of displacement will determine whether
      surgical intervention should be considered. Complications can occur in fractures
      that are undiagnosed or improperly evaluated. The purpose of this article is to
      describe imaging features of traumatic scapular injury, and discuss the role of
      diagnostic imaging in clinical decision making after shoulder trauma.

PMID- 29350641
TI  - Traumatic fractures in adults: missed diagnosis on plain radiographs in the
      Emergency Department.
AB  - Radiography remains the imaging standard for fracture detection after trauma. The
      radiographic diagnosis of most fractures and dislocations poses little difficulty
      to radiologists: however, occasionally these injuries are quite subtle or even
      impossible to detect on radiographs. Missed diagnoses of fracture potentially
      have important consequences for patients, clinicians, and radiologists.
      Radiologists play a pivot role in the diagnostic assessment of the trauma
      patients: emergency radiologists who are more practiced at seeking out and
      discerning traumatic fractures can provide an invaluable service to their
      clinical colleagues by ensuring that patients do not endure delayed diagnoses.
      This is a narrative review article aims to highlight the spectrum of fractures in
      adults potentially missed on plain radiographs, the causes of error in diagnosis
      of fractures in the emergency setting and the key elements to reduce misdiagnosis
      of fractures.

PMID- 29350642
TI  - Acute and overuse elbow trauma: radio-orthopaedics overview.
AB  - The correct management of acute, subacute and overuse-related elbow pathologies
      represents a challenging diagnostic and therapeutic problem. While major trauma
      frequently requires a rapid surgical intervention, subluxation and minor trauma
      allow taking more time for diagnostics and planning the correct elective
      treatment after careful clinical and radiological investigation. In these
      conditions, communication between orthopaedic surgeon and radiologist allow to
      create a detailed radiology report, tailored to the patient's and surgeon's needs
      and optimal to plan proper management. Imaging technique as X-Ray, CT, US, MRI,
      CTA and MRA all belong to the radiologist's portfolio in elbow diagnostics.
      Detailed knowledge of elbow pathology and its classification and of the
      possibilities and limits of each imaging technique is of crucial importance to
      reach the correct diagnosis efficiently. The aim of this review is to present the
      most frequent elbow pathologies and suggest a suitable diagnostic approach for
      each of them.

PMID- 29350643
TI  - Calcaneal fractures: radiological and CT evaluation and classification systems.
AB  - BACKGROUND AND AIM OF THE WORK: The calcaneus, the more lower bone of the body,
      has the task of supporting the axial load from the weight of the body. Calcaneal
      fractures represent about 1-2% of all fractures and 60% of the tarsal bones
      fractures. The articular involvement has been associated with a poor functional
      outcome. The aim of this work is to describe the radiologic evaluation, the
      classification systems, the morphological preoperative diagnostic imaging
      features of calcaneal fractures, highlighting the correlation with the choice of
      treatment and predictive capacity for the fracture surgical outcome. METHODS: A
      PubMed search was performed for the terms Imaging calcaneus fracture, selecting
      articles in English language, published in the last two years, where
      preoperatively diagnostic imaging of fractures of the calcaneus are described. 
      Case reports have not been included. RESULTS: We have collected a number of data
      that provide important help in preoperative evaluation of calcaneal fractures,
      such as the new classification system created by Harnroongroj et al, the
      association of calcaneal fractures with fractures of other bone structures or
      soft tissue impairment, the use of calcaneotalar ratio in assessing the length of
      heel. CONCLUSIONS: These data suggest an approach geared to the specific choice
      of treatment and to improving patient outcomes.

PMID- 29350644
TI  - Talar fractures: radiological and CT evaluation and classification systems.
AB  - INTRODUCTION: The talus is the second largest bone of the foot. It is fundamental
      to ensure normal ankle-foot movements as it connects the leg and the foot. Talar
      fractures are usually due to high energy traumas (road accidents, high level
      falls). They are not common as they account for 3-5% of ankle and foot fractures
      and 0.85% of all body fractures. However, talar fractures not correctly diagnosed
      and treated can lead to avascular necrosis of the astragalus, pseudoarthrosis,
      early osteoarthrisis and ankle instability, declining the quality of life of
      patients. METHODS: A PubMed search was performed using the terms "talus" "talus
      AND radiology", "talar fractures", and "talar fractures classification",
      selecting articles published in the last 98 years. We selected articles about pre
      treatment and post-surgery talar fractures diagnostic imaging. We also selected
      articles about talar fractures complications and traumatic talar dislocations.
      Case reports have not been included. AIM OF THE WORK: to describe radiological
      evaluations, classification systems, and biomechanical patterns involved in talar
      fractures. Also we will briefly describe talar fractures complications and
      treatment option and strategies. CONCLUSIONS: This work suggests a radiological
      approach aimed to classify talar fractures and guide treatment strategies,
      improving patient outcomes.

PMID- 29350645
TI  - Developments in the management of bone metastases with interventional radiology.
AB  - Interventional radiology has known an exponential growth in the last years.
      Technological advances of the last decades, have made it possible to use new
      treatments on a larger scale, with safe and effective results. They could be
      considered as palliative treatments for painful lesions but also curative
      procedures, as single treatment or specially in combination with other techniques
      (surgery, radiation and oncology therapies, etc.).The main diffuse techniques are
      those of thermal ablation that destroy the target lesion through the heat;
      however there are also endovascular therapies that destroy the target tissue
      thanks to devascularization. Finally the is also the possibility to stabilize
      pathological fractures or impending fractures. In this paper all the most diffuse
      and effective techniques are reviewed and also a discussion of the main
      indications is done, with an analisys of the success and complications rates.

PMID- 29350646
TI  - Radiofrequency ablation of osteoid osteoma.
AB  - Osteoid osteoma is a benign bone neoplasm with a reported incidence of 2-3% among
      all bone primary tumors. Although it is a small and benign lesion, it is often
      cause of patient complaint and discomfort. It is generally characterized by a
      long lasting, unremitting pain that typically exacerbates at night, often leading
      to sleep deprivation and functional limitation of the skeletal segment involved,
      with a significant reduction of patient daily life activities and consequent
      worsening of the overall quality of life. Over decades, complete surgical
      resection has represented the only curative treatment for symptomatic patients.
      In the last years, new percutaneous ablation techniques, especially
      radiofrequency ablation, have been reported to be a safe and effective
      alternative to classical surgery, with a low complication and recurrence rate,
      and a significant reduction in hospitalization cost and duration. The aim of this
      article is to provide an overview about the radiofrequency thermal ablation
      procedure in the treatment of osteoid osteoma.

PMID- 29350647
TI  - Rotator cuff calcific tendinopathy: from diagnosis to treatment.
AB  - Rotator cuff calcific tendinopathy (RCCT) is a very common condition caused by
      the presence of calcific deposits in the rotator cuff (RC) or in the subacromial
      subdeltoid (SASD) bursa when calcification spreads around the tendons. The
      pathogenetic mechanism of RCCT is still unclear. It seems to be related to cell
      mediated disease in which metaplastic transformation of tenocytes into
      chondrocytes induces calcification inside the tendon of the RC. RCCT is a
      frequent finding in the RC that may cause significant shoulder pain and
      disability. It can be easily diagnosed with imaging studies as conventional
      radiography (CR) or ultrasound (US). Conservative management of RCCT usually
      involves rest, physical therapy, and oral NSAIDs administration. Imaging-guided
      treatments are currently considered minimally-invasive, yet effective methods to
      treat RCCT with about 80% success rate. Surgery remains the most invasive
      treatment option in chronic cases that fail to improve with other less invasive
      approaches.

PMID- 29350648
TI  - Imaging of metabolic bone disease.
AB  - Osteoporosis is the most important metabolic bone disease, with a wide
      distribution among the elderly. It is characterized by low bone mass and micro
      architectural deterioration of bone tissue, leading to enhanced bone fragility
      and a consequent increase in fracture risk. Identify bone weakening with an
      appropriate and accurate use of diagnostic imaging is of critical importance in
      the diagnosis and follow-up of osteoporotic patients. The aim of this review is
      to evaluate the detection rates of the different imaging modalities in the
      evaluation of bone strength, in the assessment of fracture risk and in the
      management of fragility fractures.

PMID- 29350649
TI  - Magnetic Resonance Imaging in degenerative disease of the lumbar spine: Fat
      Saturation technique and contrast medium.
AB  - PURPOSE: To examine both anterior and posterior elements of the lumbar spine in
      patients with low back pain using MRI T2-weighted sequences with Fat Saturation
      (FS) and contrast enhanced T1-weighted sequences with FS. MATERIALS AND METHODS:
      Two thousand eight hundred and twenty (2820) patients (1628 male, 1192 female,
      mean age 54) presenting low back pain underwent MRI standard examination
      (Sagittal T1w TSE and T2w TSE, axial T1 SE) with the addition of sagittal and
      axial T2w Fat Sat (FS) sequences. Among all the patients, 987 (35%) have been
      studied adding Contrast Enhanced (CE) T1w FS sequences after administration of
      contrast medium. RESULTS: Among 987 patients studied with contrast medium, we
      found: active-inflammatory intervertebral osteochondrosis in 646 (65%) patients;
      degenerative-inflammatory changes in facet joints (facet joint effusion,
      synovitis, synovial cysts) in 462 (47%); spondylolysis in 69 (7%); degenerative
      inflammatory changes of the flava, interspinous and supraspinous ligaments in 245
      (25%); inflammatory changes of posterior perispinal muscles in 84 (8%) patients.
      CONCLUSIONS: In patients with suspected no-disc-related low back pain, the
      implementation of T2w FS and CE T1w FS sequences to the standard MR protocol
      could allow a better identification of degenerative-inflammatory changes more
      likely associated to the pain.

PMID- 29350650
TI  - Clinical and instrumental assessment of herniated discs after nucleoplasty: a
      preliminary study.
AB  - BACKGROUND AND AIM: The therapy for low back pain boasts different approaches;
      one of these is nucleoplasty. We wanted to assess the effectiveness of
      nucleoplasty both by clinical response both by MR imaging evaluation, including
      even extrusions larger than one third of the spinal canal. METHODS: Fifty-seven
      patients were treated with nucleoplasty in our hospital, 11 of these patients
      accepted both clinical and MRI evaluation after six months from treatment. The
      clinical evaluation was performed with Visual Analogue Scale (VAS) of pain,
      scored before and after the procedure. MRI evaluation consisted of analysing some
      imaging parameters of disc protrusions before and after the treatment. RESULTS:
      In 10 out of 11 (91%) patients, VAS was reduced and only 1 out of 11 (9%) had the
      same pain after procedure. The mean of decrease of VAS score was 64%. In our
      population 8/11 (72%) patients had a herniation larger than 1/3 of the sagittal
      diameter of spinal canal and 100% of them had an improvement with a mean VAS
      reduction value of 75%. With MRI evaluation, the mean percentage of expulsion
      before and after treatment was respectively 40% and 34%. The expulsion decreased
      in 7/13 discs, remained equal in 4/13, and increased in 2/13 discs. Among the 9
      larger protrusions, 3 didn't change, 6 reduced with a decrease mean value of 13%.
      Other MRI parameters didn't change significantly. CONCLUSIONS: Our preliminary
      experience supports the success of coblation on pain relief, aiming to show
      progressively that this treatment is suitable even in case of great extrusions,
      which are generally treated only with surgical approach. It's not clear the
      usefulness of MRI control yet, even if in most of cases we could have found a
      certain reduction of expulsion degree.

PMID- 29350651
TI  - Birth of a new Journal section on Emergency Medicine.
AB  - Not available.

PMID- 29350652
TI  - Complications associated with brachioplasty: a literature review.
AB  - BACKGROUND: Paralleling the growth of bariatric surgery, the demand for post
      bariatric body-contouring surgery is increasing. Weight loss is the main cause,
      although not the only one, that drives patients to arm lift surgery. Several
      surgical techniques have been proposed over the years. Our aim was to consider
      the complications and outcomes according to the performed technique, through a
      wide review of the literature. METHODS: A search on PubMed/Medline was performed
      using "brachioplasty", "upper arm lifting", and "techniques" as key words.
      Embase, Medline (OvidSP), Web of Science, Scopus, PubMed publisher, Cochrane, and
      Google Scholar were searched as well. As inclusion criteria, we selected the
      clinical studies describing techniques of brachioplasty. We excluded the papers
      in which complications related to brachioplasty were not specified. We also
      excluded literature-review articles. RESULTS: We found 27 studies from 1995 to
      2015. Overall, 1065 patients were treated. Different techniques were applied.
      Complications were observed in 308/1065 patients (28.9%). The most frequent
      complications were hypertrophic scarring, seroma and hematoma. Surgical revision
      rate ranged from 0 to 21 percent. Nerve damage occurred in a modest percentage of
      patients (16/1065, 1.5%). No major complications, such as thromboembolism and
      sepsis, were observed. CONCLUSIONS: Brachioplasty is a safe surgical procedure.
      All the brachioplasty techniques showed positive outcomes, in term of patients'
      satisfaction and clinical results. Nevertheless, minor complications occurred in
      a high percentage of patients, regardless the performed surgical procedure.
      Patients should be informed about the possible formation of hypertrophic scars
      and nerve injuries.

PMID- 29350653
TI  - The law on artificial insemination: an italian anomaly.
AB  - The law on medically assisted procreation in Italy, from its entering into force,
      has undergone numerous amendments. This has been due to the fact that those
      citizens, directly affected by its imposed prohibitions, have not given in,
      bringing their requests before the courts, both nationally and internationally.
      Over the years, the courts through numerous rulings have significantly changed a
      law clearly incapable of protecting the rights of those involved. Currently Italy
      has an acceptable law on M.A.P. which is the result of the strong willing of
      citizens affected by problems of sterility or infertility. The aim of this paper
      is to present an historical summary of the troubled path which the issue, from
      every perspective, has faced and is still facing today. As well, it will document
      how, in Italy, the case-law and, therefore, the law's interpretation and
      application by the judges have contributed, in the end, to shaping a positive
      legislation.

PMID- 29350654
TI  - Autolytic debridement and management of bacterial load with an occlusive
      hydroactive deressing impregnated with polyhexamethylene biguanide.
AB  - BACKGROUND: Debridement and control of bacterial load are key-points of wound
      care. The aim of this study is to evaluate the effectiveness of autolytic
      debridement and management of bacterial load (bioburden) of an occlusive hydro
      active dressing impregnated with polyhexamethylene biguanide (PHMB). METHODS: We
      used an occlusive dressing of hydro-active for leg ulcers' treatment (TenderWet
      plus(r) - Hartmann).  Inclusion criteria were: presence of a fibrinous ulcer with
      multiple etiopathogenesis, in absence of clinical infection, no hypersecretion
      and diameter within 5 cm. Swab for bacterial bioburden control were made at start
      of the study, after 3 and 7 days. We made also a measurement of the amount of
      granulation tissue and of pain with VAS scale; bacterial bioburden control inside
      the dressing was made too. RESULTS: 28 leg ulcers were treated (12 venous, 5
      diabetic, 8 thraumatic, 3 mixed) in 25 patients. The ulcer has been completely
      covered with fibrin in almost all cases and the bacterial load was represented
      mainly by Staphylococcus aureus (80% of the cases) with a load within
      10.000UFC/plate in 81,5% of the cases. Control at 3 and 7 days have shown the
      appearance of granulaton tissue up to 67,8% of the wound surface. Bacterial
      bioburden (load) remained constant in 50% of the cases, decreased in 15%,
      increased in 35% of the cases. CONCLUSION: TenderWet-plus(r) has proven to be
      effective and quick in autolytic debridement and at the same time be able to
      handle the bacterial load in most cases. It can then be used for home treatment.

PMID- 29350655
TI  - BRASS score and complex discharge: a pilot study
AB  - AIMS: A highly functional continuity of patient care, which is linked to the
      reduction of the risk of long-term hospitalization, above all for 'at-risk'
      patients. Research into an objective, reliable instrument for redirecting
      individual results to organizational aims to extend the entire country, is a
      fundamental step to move from a reactive assistance approach to a pro-active one.
      METHODS: An observational and descriptive retrospective study was carried out
      July - November 2014 in two Italian state hospitals, completing the BRASS Index
      within 48/72 hours of admission. RESULTS: The study group consisted of 122
      inpatients. A correlation presented itself, albeit low (n=0.05191), between age
      and the number of 'revolving door' admissions; a medium correlation (n=0.485131)
      between age and risk band (according to BRASS). CONCLUSIONS: The BRASS Index is
      straightforward and swift, and can prove a valuable tool in directing nurses'
      attention to those patients most at risk of prolonged hospitalization.

PMID- 29350656
TI  - Italian version of Dyspnoea-12: cultural-linguistic validation, quantitative and
      qualitative content validity study.
AB  - BACKGROUND: Dyspnoea-12 is a valid and reliable scale to assess dyspneic symptom,
      considering its severity, physical and emotional components. However, it is not
      available in Italian version due to it was not yet translated and validated. For
      this reason, the aim of this study was to develop an Italian version Dyspnoea-12,
      providing a cultural and linguistic validation, supported by the quantitative and
      qualitative content validity. METHODS: This was a methodological study, divided
      into two phases: phase one is related to the cultural and linguistic validation,
      phase two is related to test the quantitative and qualitative content validity.
      Linguistic validation followed a standardized translation process. Quantitative
      content validity was assessed computing content validity ratio (CVR) and index (I
      CVIs and S-CVI) from expert panellists response. Qualitative content validity was
      assessed by the narrative analysis on the answers of three open-ended questions
      to the expert panellists, aimed to investigate the clarity and the pertinence of
      the Italian items. RESULTS: The translation process found a good agreement in
      considering clear the items in both the six involved bilingual expert translators
      and among the ten voluntary involved patients. CVR, I-CVIs and S-CVI were
      satisfactory for all the translated items. CONCLUSIONS: This study has
      represented a pivotal step to use Dyspnoea-12 amongst Italian patients. Future
      researches are needed to deeply investigate the Italian version of  Dyspnoea-12
      construct validity and its reliability, and to describe how dyspnoea components
      (i.e. physical and emotional) impact the life of patients with cardiorespiratory
      diseases.

PMID- 29350657
TI  - An ICET- A survey on Hypoparathyroidism in Patients with Thalassaemia Major and
      Intermedia: A preliminary report.
AB  - Hypoparathyroidism (HPT) is a rare disease with leading symptoms of hypocalcemia,
      associated with high serum phosphorus levels and absent or inappropriately low
      levels of parathyroid hormone (PTH). In patients with thalassemias it is mainly
      attributed to transfusional iron overload, and suboptimal iron chelation therapy.
      The main objectives of this survey were to provide data on the prevalence,
      demographic and clinical features of HPT in thalassemia major (TM) and intermedia
      (TI) patients living in different countries, and to assess its impact in clinical
      medical practice. A questionnaire was sent to all Thalassemia Centres
      participating to the International Network of Clinicians for Endocrinopathies in
      Thalassemia and Adolescence Medicine (ICET-A) Network.Seventeen centers, treating
      a total of 3023 TM and 739 TI patients, participated to the study. HPT was
      reported in 206 (6.8%) TM patients and 33 (4.4%) TI patients. In general, ages
      ranged from 10.5 to 57 years for the TM group and from 20 to 54 years for the TI
      group. Of the 206 TM patients and 33 TI patients with HPT, 117 (48.9%) had a
      serum ferritin level >2.500 ng/ml (54.3% TM and 15.1% TI patients) at the last
      observation. Hypocalcemia varied in its clinical presentation from an
      asymptomatic biochemical abnormality to a life-threatening condition, requiring
      hospitalization. Calcium and vitamin D metabolites are currently the cornerstone
      of therapy in HPT. In TM patients, HPT was preceded or followed by other
      endocrine and non-endocrine complications. Growth retardation and hypogonadism
      were the most common complications (53.3% and 67.4%, respectively). Although
      endocrine complications were more common in patients with TM, non-transfused or
      infrequently transfused patients with TI suffered a similar spectrum of
      complications but at a lower rate than their regularly transfused counterparts.In
      conclusion, although a large international registry would help to better define
      the prevalence, comorbidities and best treatment of HPT, through the result of
      this survey we hope to give a clearer understanding of the burden of this disease
      and its unmet needs. HPT requires lifelong therapy with vitamin D or metabolites
      and is often associated with complications and comorbidities.Therefore, it is
      important for endocrinologists and other physicians, who care for these patients,
      to be aware of recent advances of this disorder.

PMID- 29350658
TI  - Experience of Oesophageal atresia management in a tertiary Bangladeshi hospital.
AB  - OBJECTIVES: Background and aim: This study has been conducted to determine the
      clinical presentations and surgical outcome of patients with OA admitted in a
      tertiary level hospital in Bangladesh. METHODS: A prospective analysis was
      conducted for 32 patients with confirmed OA between July 2007 and June 2015. Of
      them surgical correction was done in 25 cases. The other 7, in whom surgery could
      not be done, were excluded from the study. RESULTS: Of the 25 cases, that had
      been operated, 15 were full term and 52% were more than 48 hours old. Type-C OA
      with TOF was the commonest type (96%). 24 cases were operated through Right
      Thoracotomy. Of them 52% were done by Single Lung (left) ventilation. 'Division
      of the fistula' with 'end to end anastomosis' was done in all of them. Only 1
      patient had a Gastric pull up surgery. Of the 25 cases, 16 survived (64%). In
      follow up all the patients were found thriving and showed no problem in
      swallowing. CONCLUSION: Our study which shows 64% survival is a great achievement
      for us but not satisfactory in international standard. However, the experience
      and encouragement that we are gathering, will guide us to achieve better result
      in near future.

PMID- 29350659
TI  - Thiopental is better than propofol for electroconvulsive therapy.
AB  - BACKGROUND AND AIM OF THE WORK: electroconvulsive therapy is a psychiatric
      procedure requiring general anesthesia. The choice of the hypnotic agent is
      important because the success of the intervention is associated to the occurrence
      and duration of motor convulsion. However, all available anesthetic agents have
      anti-convulsant activity. We compared the effect of thiopental and propofol on
      seizures. METHODS: We designed a retrospective study at Mood Disorders Unit of a
      teaching Hospital. Fifty-six consecutive patients undergoing electroconvulsive
      therapy were enrolled. Patients received fentanyl followed by either thiopental
      or propofol. We evaluated the incidence and the duration of seizure after
      electric stimulus at the first session of electroconvulsive therapy for each
      patient. Adverse perioperative effects were recorded. RESULTS: Patients were 60+/
      12.1 years old and 64% was female. There was a statistically significant higher
      number of patients who had motor convulsion activity in the thiopental group when
      compared to the propofol group (25 vs 13, p=0.023). Seizure duration was
      statistically significant longer in the thiopental group than in the propofol
      group (35 sec vs 11 sec, p=0.046). No hemodynamic instability, oxygen
      desaturation episodes, prolonged recovery time from anesthesia and adverse
      effects related to anesthesia were recorded. CONCLUSIONS: Thiopental induction
      has a favourable effect on seizure when compared to propofol in patients
      undergoing electroconvulsive therapy.

PMID- 29350660
TI  - Rest 2D speckle tracking echocardiography may be a sensitive but nonspecific test
      for detection of significant coronary artery disease.
AB  - AIMS: To detect the significance of coronary artery disease in the patients, who
      are suspected, was assumed to be one of the advantages of 2D STE, as a novel non
      invasive imaging modality with acceptable accuracy. METHODS: In this study, 216
      patients who were suspected to have coronary artery disease and candidate for
      coronary angiography, underwent rest two-dimensional speckle tracking
      echocardiography (2D STE) and negative global systolic longitudinal strain was
      evaluated. RESULTS: Negative global systolic left ventricular longitudinal strain
      under 18% in rest 2D-STE was significantly prevalent in patients with significant
      CAD in coronary angiography (P value<0.0001).Our results revealed sensitivity of
      91.1%, specificity of 63.0%, positive predictive value of 80.4%, negative
      predictive value of 81.0% and accuracy of 80.5% for rest 2D-STE in detection of
      significant CAD. CONCLUSION: Here in we showed that rest Two-dimensional speckle
      tracking echocardiography could be a sensitive but nonspecific imaging modality
      to determine significant coronary artery disease. Future studies with large size
      will reveal more detailed findings.

PMID- 29350661
TI  - Retrospective analysis of the effects of a highly standardized mixture of
      Berberis aristata, Silybum marianum, and monacolins K and KA in diabetic patients
      with dyslipidemia.
AB  - BACKGROUND: Berberine, an alkaloid with both glucose- and cholesterol-lowering
      action, is also characterized by an anti-diarrheal effect. Consequently,
      berberine-based therapies are recommended for diabetic patients with irritable
      bowel syndrome (IBS) or gut discomfort caused by metformin. AIM: As the anti
      glycemic and cholesterol-lowering action of berberine is improved by co
      administration with P-glycoprotein inhibitors and naturally derived statins, we
      have analyzed the effect of the food supplement Berberol(r)K (hereafter referred
      to as BSM) containing, berberine, silymarin, and a highly standardized red yeast
      rice containing monacolins K and KA in the ratio 1:1 but no secondary monacolins,
      dehydromonacolins, or citrinin (MonakopureTM-K20). METHODS: We retrospectively
      evaluated the effects of BSM in 59 diabetic patients with dyslipidemia and
      compared the results to those obtained in patients without treatment. Enrolled
      subjects had a diagnosis of IBS (and diarrhea), had diarrhea caused by metformin,
      or were statin intolerant. RESULTS: After 6 months of BSM treatment, significant
      reductions of approximately 5%, 23%, 31%, and 20% were observed in glycated
      hemoglobin (HbA1c), total cholesterol (TC), low density lipoprotein-cholesterol
      (LDL), and triglyceride (TG) levels, respectively, and only five of the 31
      treated subjects reported diarrhea compared with 22 of the 28 untreated patients.
      Regarding safety, treatment with BSM did not significant modify creatine
      phosphokinase (CPK), creatine, aspartate aminotransferase (AST) or alanine
      aminotransferase (ALT). CONCLUSION: BSM is a safe and effective food supplement
      likely useful as add-on therapy in diabetic subjects with dyslipidemia,
      especially if they are statin intolerant or with diarrhea caused by IBS or
      metformin.

PMID- 29350662
TI  - High protein intake in human/maternal milk fortification for <=1250 gr infants:
      intrahospital growth and neurodevelopmental outcome at two years.
AB  - BACKGROUND AND AIM OF THE STUDY: Extrauterine growth restriction and failure to
      thrive remain a major problem in Extremely Low Birth Weight infants. Nutritional
      support in preterm babies has the objective to improve the achieve rate of growth
      similar to those of the fetus in utero at the equivalent gestational age. The aim
      of the study was to evaluate feeding tolerance, intrahospital growth,
      neurological outcome and anthropometric data until 24 months of corrected age
      (mca) from different protein intake assumed by preterm babies <1250 g during
      their stay in NICU. METHODS: The study evaluates auxological/neurodevelopmental
      outcomes until 24 months of corrected age (mca) in preterm infants with different
      protein intake (control group-CG: 3,5g Kg?1 perday; intervention group-PSG: 4,8g
      Kg?1 per day). RESULTS: PSG group showed a significant higher length growth at 9
      mca (p 0,04) and hearing/language score of Griffiths Mental Development Score
      (GMDS) at 12 (p 0,03) and 18 mca  (p<0,05) comparing with CG. PSG-ELBW preterms
      showed an higher intrahospital head circumference (p 0,02) and length growth rate
      (p 0,04), greater Performance (p 0,04) and Hearing/Language (p 0,03) scores of
      GMDS at 3 and 12 mca. PSG-SGA preterms showed significantly higher scores in GMDS
      scores at 18 and 24 mca except for the locomotor domain. CONCLUSIONS:
      Supplemental enteral proteins lead to benefits of reduced postnatal growth
      restriction and better neurological outcome in preterm infants <1000 g and in
      those SGA <1250 g.

PMID- 29350663
TI  - Effectiveness of a tailored medical support to overcome the barriers to
      education, treatment and good metabolic control in children with type-1 diabetes
      from ethnic minorities.
AB  - AIM: To analyze the effectiveness of a tailored medical support to help children
      from ethnic minorities to achieve the same good metabolic control of
      autochthonous peers with type-1 diabetes (T1D). METHODS: Children <10 years of
      age belonging to ethnic minority (EM) families (Group 1) were compared with
      autochthonous peers (Group 2) who received the diagnosis of T1D in 2014-2016. The
      Protocol for minorities included other than the standard protocol: booklets
      translated in ethnic minority languages; weekly visits at home or at school;
      family-guides; clinic visits supported by professional interpreters. After twelve
      months of this approach, parents of ethnic minority children answered a short
      questionnaire concerning satisfaction about educational tools for diabetes
      management. RESULTS: From 1st January 2014 to December 31st 2016, 72 children
      received the diagnosis of T1D at the University Children Hospital of Parma,
      Italy. Nineteen children belonged to an EM family (26.38%), and were included in
      the Group 1. Twenty-one autochthonous peers were randomly recruited for the Group
      2. T1D was diagnosed at the same mean age in Group 1 (5.2+/-2.2) and in Group 2
      patients (5.7+/-2.4). Metabolic derangements at diagnosis were more severe in
      Group 1 than in Group 2 patients. However, patients of both Groups showed a
      similar decrease in HbA1c levels during the first 3 and 6 months post diagnosis.
      Patients did not differ in mean insulin doses at discharge and at follow up. The
      calls to the emergency toll-free telephone number were more numerous from the
      parents from Group 1 than from the parents of Group 2. Total cost to implement
      the tailored protocol in Group 1 was higher of 87% compared with the standard
      protocol used for Group 2 patients. Great majority of parents reported to be
      satisfied with the provided diabetes education program. CONCLUSIONS: The results
      of this study suggested that children from EM families can achieve the same good
      metabolic control of autochthonous peers with T1D, providing a cost-effective
      tailored support to their family members.

PMID- 29350664
TI  - Synovial cysts of the hip.
AB  - BACKGROUND: Synovial cysts of the hip are relatively rare lesions comparing to
      other joints. Patients are usually asymptomatic, but in some cases symptoms such
      as pain and/or compression of vessels or nerve could be present. Purpose of the
      study was to define clinical features and optimal management of synovial cyst of
      the hip joint through an accurate review of the literature. METHODS: We present
      three consecutive cases treated with three different therapeutic strategies:
      surgical excision, wait-and-see and needle aspiration. An accurate review of the
      literature has been performed to identify patients who had been treated for
      synovial cyst of the hip. RESULTS: Due to the rarity of the disease, there are no
      significant data in literature supporting the gold standard of treatment.
      Treatment of the synovial cyst depends on their size, symptoms and comorbidities.
      CONCLUSIONS: Most of the Authors recommend surgical treatment for symptomatic
      synovial cysts and needle aspiration as an option treatment in asymptomatic
      patients without vessel or nerve compression. In patients that referred symptoms
      in correspondence with the hip joint, not strictly related with radiograph
      findings, a CT or MRI examinations should be performed to exclude possible
      differential diagnosis.

PMID- 29350665
TI  - Laparoscopic gastric bypass with remnant gastrectomy in a super-super obese
      patient with gastric metaplasia: a surgical hazard?
AB  - The endoscopic inaccessibility of the gastric remnant after Roux-en-Y gastric
      bypass (RYGBP) for morbid obesity represents an important issue for patients with
      familiar history of gastric cancer (GC) or affected by premalignant lesions, such
      as intestinal metaplasia. If a different bariatric procedure is contraindicated,
      RYGBP with remnant gastrectomy represents a reasonable alternative, significantly
      reducing the risk of GC but potentially increasing postoperative morbidity. For
      this reason, only few cases have been reported in the recent Literature and none
      regarding a super-super obese patient. We present the case of a 55-year-old super
      super obese man with a family history of GC and antral gastritis with extensive
      intestinal metaplasia at preoperative upper endoscopy, who underwent laparoscopic
      RYGBP with remnant gastrectomy.

PMID- 29350666
TI  - Melanoma in situ mimicking a Lichen planus-like keratosis.
AB  - The incidence of melanoma has steadily increased over the past three decades.
      Melanoma in situ (MIS),  defined as melanoma that is limited to the epidermis,
      contributes to a disproportionately high percentage of this rising incidence.
      Amelanotic melanoma presents as an erythematous macule or plaque and may
      initially be misdiagnosed as an inflammatory disorder. We report a case of
      amelonatic MIS raised on non-sun-exposed skin, inducing a lichen planus-like
      keratosis as inflammatory reaction, which clinically masked the melanoma.

PMID- 29350667
TI  - The Schmidt Syndrome.
AB  - Addison's disease (AD) is a rare endocrine condition related to adrenal
      insufficiency. Autoimmune adrenalitis is commonly associated with autoimmune
      diseases. Autoimmune Addison's Disease (AAD) describes Autoimmune Polyendocrine
      Syndrome (APS) in 60% of patients with an important immunitary pathogenesis
      imprinting. We describes a case of Autoimmune Polyendocrine Syndrome
      charachterize by adrenal insufficiency and thyroid disease (Schmidt Syndrome). In
      this case report, Addison's disease had a slow onset in absence of the typical
      weight loss. In our considerations this is due to the concomitant hypothyroidism
      that masked some typical signs and also limited acute presentation.

PMID- 29350668
TI  - Concealed lung anatomy in Botticelli's masterpieces the primavera and the birth
      of venus.
AB  - Sandro Botticelli was one of the most esteemed painters and draughtsmen among
      Renaissance artists. Under the patronage of the De' Medici family, he was active
      in Florence during the flourishing of the Renaissance trend towards the
      reclamation of lost medical and anatomical knowledge of ancient times through the
      dissection of corpses. Combining the typical attributes of the elegant courtly
      style with hallmarks derived from the investigation and analysis of classical
      templates, he left us immortal masterpieces, the excellence of which
      incomprehensibly waned and was rediscovered only in the 1890s. Few know that it
      has already been reported that Botticelli concealed the image of a pair of lungs
      in his masterpiece, The Primavera. The present investigation provides evidence
      that Botticelli embedded anatomic imagery of the lung in another of his major
      paintings, namely, The Birth of Venus. Both canvases were most probably
      influenced and enlightened by the neoplatonic philosophy of the humanist
      teachings in the De' Medici's circle, and they represent an allegorical
      celebration of the cycle of life originally generated by the Divine Wind or
      Breath. This paper supports the theory that because of the anatomical knowledge
      to which he was exposed, Botticelli aimed to enhance the iconographical meaning
      of both the masterpieces by concealing images of the lung anatomy within them.

PMID- 29350669
TI  - An Osteological Museum inside the Varese Medical School? A proposal from the
      Medical, Antropological and Paleopatological point of view.
AB  - Not available.

PMID- 29350670
TI  - Medical Humanities. Recognition and reorganization within the Italian University.
AB  - Not available.

PMID- 29350671
TI  - Visits for alcohol-related problems in a large urban Emergency Department.
      Results of a 15-year survey.
AB  - Alcohol abuse is associated with a high burden of morbidity and mortality.
      Nevertheless, definitive epidemiological data on alcohol-related visits in the
      emergency department (ED) is substantially lacking. This study was aimed to
      analyze the epidemiological patterns and temporal trends of alcohol-related
      visits in the local ED, and assessing the healthcare burden of cases needing
      hospital admission. All patients visited for alcohol-related problems between the
      years 2002-2016 were anonymously identified from the hospital database. All cases
      were classified according to the main cause leading to ED, age and gender, time
      of presentation, disposition. Overall, 8014 cases were identified (2249 women and
      5765 men). Women were younger than men. The overall trend during the study period
      was characterized by a constant increase in the number of alcohol-related ED
      admissions. A significant number of subjects had multiple alcohol-related visits.
      A total number of 747 patients were visited twice, 259 three times and 107 four
      times. A mostly nocturnal pattern of ED presentation was observed in both
      genders, peaking between midnight and 2 AM, and an increased number of visits was
      recorded during the weekends. The vast majority of patients (64%) could be
      discharged within 6 hours, but a considerable number needed longer observation
      and treatment in the ED. Overall, 7551 patients were discharged from the ED,
      whilst 462 patients needed hospital admission, 179 for traumatic injuries and 283
      for non-traumatic causes. The decreasing age of subjects admitted to the ED with
      alcohol-related problems should now be regarded as a public healthcare issue.

PMID- 29350672
TI  - Rebounds after discharge from the emergency department for community-acquired
      pneumonia: focus on the usefulness of severity scoring systems.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is common cause of hospital
      admission and leading cause of morbidity and mortality. Severity scoring systems
      are used to predict risk profile, outcome and mortality, and to help decisions
      about management strategies. Aim of the work and Methods: To critically analyze
      pneumonia "rebound" cases, once discharged from the emergency department (ED) and
      afterwards admitted. We conducted an observational clinical study in the acute
      setting of a university teaching hospital, prospectively analyzing, in a 1 year
      period, demographic, medical, clinical and laboratory data, and the outcome.
      RESULTS: 249 patients were discharged home with diagnosis of CAP; 80 cases
      (32.1%) resulted in the high-intermediate risk class according to CURB-65 or CRB
      65. Twelve patients (4.8%) presented to the ED twice and were then admitted. At
      their first visit 5 were in the high-intermediate risk group; just 4 of them were
      in the non-low risk group at the time of their admission. The rebound cohort
      showed some peculiar abnormalities in laboratory parameters (coagulation and
      renal function) and severe chest X-rays characteristics. None died in 30 days.
      CONCLUSIONS: The power of CURB-65 to correctly predict mortality for CAP patients
      discharged home from the ED is not confirmed by our results; careful clinical
      judgement seems to be irreplaceable in the management process. Many patients with
      a high-intermediate risk according to CURB-65 can be safely treated as
      outpatients, according to adequate welfare conditions; we identified a subgroup
      of cases that should worth a special attention and, therefore, a brief
      observation period in the ED before the final decision to safely discharge or
      admit.

PMID- 29350673
TI  - Glyphosate ingestion causing multiple organ failure: a near-fatal case report.
AB  - A 55 years old man self-presented to our Emergency Department (ED) reporting an
      attempted suicide by cutting the left forearm veins and ingesting approximately
      200 mL of an herbicide (Myrtos(r), containing 36% of glyphosate as isopropylamine
      salt). Laboratory tests showed metabolic acidosis. Hydration with normal saline
      and alkalinization with sodium bicarbonate was started according to suggestion of
      the poison control center, since an antidote was unavailable. Cardiorespiratory
      condition gradually worsened, so that non-invasive positive pressure ventilation
      (NIPPV) was applied and infusion of fluids was established. Nevertheless, the
      patient deteriorated and he needed to be transferred to the Intensive Care Unit
      (ICU), where he underwent orotracheal intubation and invasive mechanical
      ventilation. Noradrenaline and adrenaline were infused and fluid resuscitation
      with crystalloids was incremented. An esophagogastroduodenoscopy (EGD) showed
      diffuse mucosal erosions of upper digestive tract. No signs of visceral
      perforation were found during ICU stay. In the following days, the clinical
      conditions improved and a new EGD showed marked improvement of erosive lesions.
      After 12 days of ICU stay, the patient was extubated and then transferred to the
      Psychiatric Unit, in good clinical conditions. Gliphosate ingestion is associated
      with rapid development of multiple organ failure (MOF). Since an effective
      antidote is unavailable, major attention should be placed to aggressive life
      support care and careful monitoring of complications.

PMID- 29350674
TI  - Takotsubo cardiomyopathy in an ultra-centenarian woman.
AB  - A 101 years-old woman was admitted to our Emergency Department (ED) for acute
      dyspnea which onset nearly two hours before presentation. She had been on
      hydrochlorothyazyde-amiloride therapy due to mild hypertension. No other relevant
      features were present in the clinical history. The old lady had never been
      admitted to the hospital, and she was still living alone. A few days before
      hospital admission, one of the daughters became ill, so that a caregiver was paid
      for assisting her 12/24. This new circumstance was reluctantly accepted by the
      old lady. At ED presentation the patient was dyspnoic but alert. The
      electrocardiogram showed a marked elevation of the ST segment in V2-V6 leads. The
      echocardiogram showed the typical apical ballooning, characteristic of takotsubo
      cardiomyopathy. Blood test only showed a significant increase of cardiac troponin
      I. Considering the very good conditions of the patient, a coronary angiography
      was performed, that demonstrated a coronary tree totally free of lesions, thus
      confirming the clinical suspicion of takotsubo syndrome. The patient was admitted
      to the Coronary Care Unit, where she had a very good clinical course, and was
      discharged on day 6th after presentation. After one month of follow-up the
      clinical course was uneventful and the lady remained in good clinical and
      lifestyle conditions as before presenting to the ED. This unique case attests
      that takotsubo cardiomyopathy can be also observed at extreme ages, and should
      hence be considered in the differential diagnosis of acute dyspnea and chest pain
      in extremely elderly patients.

PMID- 29350675
TI  - Cerebellar metastasis with the cavity of both components of lung adenosquamous
      cell carcinoma.

PMID- 29350676
TI  - An increase in high-density lipoprotein cholesterol concentration after
      initiation of insulin treatment is dose-dependent in newly diagnosed type 1
      diabetes. The results of the InLipoDiab1 study.

PMID- 29350678
TI  - PIK3R3 regulates PPARalpha expression to stimulate fatty acid beta-oxidation and
      decrease hepatosteatosis.
AB  - Phosphatidylinositol 3-kinase (PI3K) signaling plays an important role in the
      regulation of cellular lipid metabolism and non-alcoholic fatty liver disease
      (NAFLD). However, little is known about the role of the regulatory subunits of
      PI3K in lipid metabolism and NAFLD. In this study, we characterized the
      functional role of PIK3R3 in fasting-induced hepatic lipid metabolism. In this
      study, we showed that the overexpression of PIK3R3 promoted hepatic fatty acid
      oxidation via PIK3R3-induced expression of PPARalpha, thus improving the fatty
      liver phenotype in high-fat diet (HFD)-induced mice. By contrast, hepatic PIK3R3
      knockout in normal mice led to increased hepatic TG levels. Our study also showed
      that PIK3R3-induced expression of PPARalpha was dependent on HNF4alpha. The novel
      PIK3R3-HNF4alpha-PPARalpha signaling axis plays a significant role in hepatic
      lipid metabolism. As the activation of PIK3R3 decreased hepatosteatosis, PIK3R3
      can be considered a promising novel target for developing NAFLD and metabolic
      syndrome therapies.

PMID- 29350677
TI  - Critical effects of long non-coding RNA on fibrosis diseases.
AB  - The expression or dysfunction of long non-coding RNAs (lncRNAs) is closely
      related to various hereditary diseases, autoimmune diseases, metabolic diseases
      and tumors. LncRNAs were also recently recognized as functional regulators of
      fibrosis, which is a secondary process in many of these diseases and a primary
      pathology in fibrosis diseases. We review the latest findings on lncRNAs in
      fibrosis diseases of the liver, myocardium, kidney, lung and peritoneum. We also
      discuss the potential of disease-related lncRNAs as therapeutic targets for the
      clinical treatment of human fibrosis diseases.

PMID- 29350679
TI  - Proangiogenic functions of an RGD-SLAY-containing osteopontin icosamer peptide in
      HUVECs and in the postischemic brain.
AB  - Osteopontin (OPN) is a phosphorylated glycoprotein secreted into body fluids by
      various cell types. OPN contains arginine-glycine-aspartate (RGD) and serine
      leucine-alanine-tyrosine (SLAY) motifs that bind to several integrins and mediate
      a wide range of cellular processes. In the present study, the proangiogenic
      effects of a 20-amino-acid OPN peptide (OPNpt20) containing RGD and SLAY motifs
      were examined in human umbilical vein endothelial cells (HUVECs) and in a rat
      focal cerebral ischemia model. OPNpt20 exerted robust proangiogenic effects in
      HUVECs by promoting proliferation, migration and tube formation. These effects
      were significantly reduced in OPNpt20-RAA (RGD->RAA)-treated cells, but only
      slightly reduced in OPNpt20-SLAA (SLAY->SLAA)-treated cells. Interestingly, a
      mutant peptide without both motifs failed to induce these proangiogenic
      processes, indicating that the RGD motif is crucial and that SLAY also has a
      role. In OPNpt20-treated HUVEC cultures, AKT and ERK signaling pathways were
      activated, but activation of these pathways and tube formation were suppressed by
      anti-alphavbeta3 antibody, indicating that OPNpt20 stimulates angiogenesis via
      the alphavbeta3-integrin/AKT and ERK pathways. The proangiogenic function of
      OPNpt20 was further confirmed in a rat middle cerebral artery occlusion model.
      Total vessel length and vessel densities were markedly greater in OPNpt20-treated
      ischemic brains, accompanied by induction of proangiogenic markers. Together,
      these results demonstrate that the 20-amino-acid OPN peptide containing RGD and
      SLAY motifs exerts proangiogenic effects, wherein both motifs have important
      roles, and these effects appear to contribute to the neuroprotective effects of
      this peptide in the postischemic brain.

PMID- 29350680
TI  - Effects of microRNA-135a on the epithelial-mesenchymal transition, migration and
      invasion of bladder cancer cells by targeting GSK3beta through the Wnt/beta
      catenin signaling pathway.
AB  - This study investigated the effects of microRNA-135a (miR-135a) targeting of
      glycogen synthase kinase 3beta (GSK3beta) on the epithelial-mesenchymal
      transition (EMT), migration and invasion of bladder cancer (BC) cells by
      mediating the Wnt/beta-catenin signaling pathway. BC and adjacent normal tissues
      were collected from 165 BC patients. Western blotting and quantitative real-time
      PCR were used to detect the expression of GSK3beta, beta-catenin, cyclinD1, E
      cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to
      blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small
      interfering RNA (siRNA)-GSK3beta or miR-135a inhibitors+siRNA-GSK3beta groups.
      miR-135a, beta-catenin, cyclinD1 and vimentin expression increased, while
      GSK3beta and E-cadherin expression decreased in BC tissues compared with adjacent
      normal tissues. Compared with the blank and NC groups, the expression of miR
      135a, beta-catenin, cyclinD1 and vimentin was higher, and cell proliferation,
      migration, invasion and tumor growth were increased in the miR-135a mimics and
      siRNA-GSK3beta groups. These groups showed an opposite trend in GSK3beta and E
      cadherin expression and cell apoptosis. The miR-135a inhibitors group was
      inversely correlated with the blank and NC groups. It was concluded that miR-135a
      accelerates the EMT, invasion and migration of BC cells by activating the
      Wnt/beta-catenin signaling pathway through the downregulation of GSK3beta
      expression.

PMID- 29350681
TI  - AAV-9 mediated phosphatase-1 inhibitor-1 overexpression improves cardiac
      contractility in unchallenged mice but is deleterious in pressure-overload.
AB  - The downregulation of beta-adrenergic receptors (beta-AR) and decreased cAMP
      dependent protein kinase activity in failing hearts results in decreased
      phosphorylation and inactivation of phosphatase-inhibitor-1 (I-1), a distal
      amplifier element of beta-adrenergic signaling, leading to increased protein
      phosphatase 1 activity and dephosphorylation of key phosphoproteins, including
      phospholamban. Downregulated and hypophosphorylated I-1 likely contributes to
      beta-AR desensitization; therefore its modulation is a promising approach in
      heart failure treatment. Aim of our study was to assess the effects of adeno
      associated virus serotype 9 (AAV9) - mediated cardiac-specific expression of
      constitutively active inhibitor-1 (I-1c) and to investigate whether I-1c is able
      to attenuate the development of heart failure in mice subjected to transverse
      aortic constriction (TAC). 6-8 week old C57BL/6 N wild-type mice were subjected
      to banding of the transverse aorta (TAC). Two days later 2.8 * 1012 AAV-9 vector
      particles harbouring I-1c cDNA under transcriptional control of a human troponin
      T-promoter (AAV9/I-1c) were intravenously injected into the tail vein of these
      mice (n=12). AAV9 containing a Renilla luciferase reporter (AAV9/hRluc) was used
      as a control vector (n=12). Echocardiographic analyses were performed weekly to
      evaluate cardiac morphology and function. 4 weeks after TAC pressure- volume
      measurements were performed and animals were sacrificed for histological and
      molecular analyses. Both groups exhibited progressive contractile dysfunction and
      myocardial remodeling. Surprisingly, echocardiographic assessment and
      histological analyses showed significantly increased left ventricular hypertrophy
      in AAV9/I-1c treated mice compared to AAV9/hRluc treated controls as well as
      reduced contractility. Pressure-volume loops revealed significantly impaired
      contractility after AAV9/I-1c treatment. At the molecular level, hearts of AAV9/I
      1c treated TAC mice showed a hyperphosphorylation of the SR Ca2+-ATPase inhibitor
      phospholamban. In contrast, expression of AAV9/I-1c in unchallenged animals
      resulted in selective enhancement of phospholamban phosphorylation and augmented
      cardiac contractility. Our data suggest that AAV9-mediated cardiac-specific
      overexpression of I-1c, previously associated with enhanced calcium cycling,
      improves cardiac contractile function in unchallenged animals but failed to
      protect against cardiac remodeling induced by hemodynamic stress questioning the
      use of I-1c as a potential strategy to treat heart failure in conditions with
      increased afterload.

PMID- 29350682
TI  - Conditional replication of oncolytic viruses based on detection of oncogenic
      mRNA.
AB  - Recently, split intein-based detection sensors for RNA have been developed that
      can target custom sequences in a modular fashion. If multi-region, multi-sample
      sequencing were to be applied to a patient's cancer, truncal (that is, earliest
      occurring) mutations could be identified and could serve as targets for these
      sense-and-respond modules. The next step would be to utilize an effective vector
      for treatment. A hyper-virulent herpes simplex virus could possibly serve as this
      vector, with concurrent immunosuppression to allow for unhindered infection of
      the tumor regions. Given that, the oncogenic mutations could serve as molecular
      'kindling', with exogenous small molecule-mediated enhancement of replication
      after initial seeding of tumors and metastases. Then, a toxin may be induced to
      destroy the cancer entirely, ideally with a bystander effect.

PMID- 29350684
TI  - East of England regional retinopathy of prematurity service: lessons from the
      first year.

PMID- 29350683
TI  - CCAT1 stimulation of the symmetric division of NSCLC stem cells through
      activation of the Wnt signalling cascade.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related
      mortalities worldwide, yet this condition remains a poorly understood malignancy,
      and the subgroup of cancer stem cells (CSCs) leading to therapeutic resistance
      and adverse prognosis have not been well studied. CSCs frequently undergo
      symmetric division, which facilitates expansion of the stem cell pool,
      contributing to long-term relapse and therapy failure. CCAT1 could act as a miRNA
      sponge to influence downstream genes; however, its roles in NSCLC stem cell are
      unclear. We first identified activation of Wnt signalling in NSCLC. Analysis of
      the clinical data from a public database showed a significant decrease of the Wnt
      signalling repressor Let-7c. Using biological and informatics analyses, we
      hypothesized that CCAT1 stimulated the main factors of the Wnt signalling
      pathway, of which the three most deregulated genes were further confirmed by
      western blotting. Axitinib, a Wnt signalling inhibitor, effectively stimulated
      asymmetric division, similar to Let-7c. CCAT1 inhibition decreased the ratio of
      symmetric division of stem cells, and both Let-7c and Axitinib significantly
      abolished CCAT1 induction of symmetric division by inhibiting Wnt signalling.
      Restoration of Let-7c blocked the CCAT1 effects, forming the CCAT1/Let-7c/Wnt
      regulatory axis to control the division of lung cancer stem cells. Stimulation of
      stem cells to divide asymmetrically by delivering Let-7c or suppressive Axitinib
      could represent prospective strategies for curing lung cancer patients.

PMID- 29350685
TI  - Re-orchestration of blood flow by micro-circulations.
AB  - Haemoglobin Video Imaging (HVI) demonstrates conjunctival and episcleral blood
      flow in man with the resolution of a single erythrocyte. A new method for
      establishing vessel hierarchy in micro-circulations is described, which
      recognises either delivery or drainage vessels and references vessel order to the
      capillary. These tools have been used to characterise blood flow.Anterior ciliary
      arteries show pulsatile variation in diameter. The episcleral arterial circle
      that they supply has functional apices with pulsatile flow reversal. Perfusion
      fields overlap: a single delivery vessel may project to many drainage vessels and
      vice-versa. Some vascular pathways remained inactive throughout a 1 min
      angiogram.Small conjunctival delivery vessels have laminar flow, but advancing
      luminal constrictions are often observed within the blood column. Laminar flow is
      lost in low-order drainage vessels where erythrocytes aggregate, but quickly
      recovers, new striae being added to the blood column at each confluence. Aqueous
      forms a discrete column, which centralises in episcleral drainage vessels.There
      is strong evidence that the luminal constrictions in small delivery vessels
      propel blood by peristalsis: they form spontaneously, remote from bifurcations; a
      single vessel may have multiple constrictions; they truly narrow the lumen,
      rarely contributing volume to post-capillary venules; they can proceed faster
      than the vessel contents; they never enter the drainage system; the trailing
      edges of erythrocyte boluses usually taper. They are rhythmically aligned with
      cardiac systole.While blood is transported to the periphery by the heart, it is
      actively transferred through tissues by peristalsis in small delivery vessels.

PMID- 29350686
TI  - Fuchs endothelial corneal dystrophy and macular drusen: evidence for coincidence?

PMID- 29350687
TI  - Intraocular currents, Bernoulli's principle and non-drainage scleral buckling for
      rhegmatogenous retinal detachment.
AB  - For many years, it is not fully understood how non-drainage scleral buckling
      surgery brings about spontaneous reattachment of the detached retina when retinal
      breaks remain open at the end of surgery. Various explanations have been put
      forward, but none more interesting than the effect of fluid currents associated
      with eye movements. One such explanation involved the physics of the Bernoulli's
      principle. Daniel Bernoulli was an eighteenth century Swiss mathematician and he
      described an equation based on the conservation of energy. The sum of pressure
      energy, potential energy and kinetic energy remains constant. Bernoulli's
      equation usually applies to closed system such as the flow of fluid through
      pipes. When fluid flows through a constriction, the speed of fluid increases, the
      kinetic energy increases. If there was no change in elevation (potential energy),
      then the increase in kinetic energy must be accompanied by a decrease in pressure
      energy. In ophthalmic surgery, the Bernoulli's effect is the basis for venturi
      pumps that drive vitrectomy and phacoemulsification machines. This essay expounds
      on how Bernoulli's effect might be relevant to scleral buckling for retinal
      detachment repair. In the era when vitrectomy is increasing the primary surgical
      operation for retinal detachment, the pervasive advice is to emphasise the
      importance of patient adopting head posture and remaining still postoperatively.
      The exception is non-drainage scleral buckling surgery. Early postoperative
      mobilisation may be vital to achieve reattachment.

PMID- 29350688
TI  - Laws of physics help explain capillary non-perfusion in diabetic retinopathy.
AB  - The purpose is to use laws of physics to elucidate the mechanisms behind
      capillary non-perfusion in diabetic retinopathy. In diabetic retinopathy, loss of
      pericytes weakens capillary walls and the vessel dilates. A dilated capillary has
      reduced resistance to flow, therefore increased flow in that vessel and decreased
      in adjoining capillaries. A preferential shunt vessel is thus formed from the
      dilated capillary and the adjacent capillaries become non-perfused. We apply the
      laws of Laplace and Hagen-Poiseuille to better understand the phenomena that lead
      to capillary non-perfusion. These laws of physics can give a foundation for
      physical or mathematical models to further elucidate this field of study. The law
      of Laplace predicts that a weaker vessel wall will dilate, assuming constant
      transmural pressure. The Hagen-Poiseuille equation for flow and the Ostwald-de
      Waele relationship for viscosity predict that a dilated vessel will receive a
      higher portion of the fluid flow than the adjoining capillaries. Viscosity will
      decrease in the dilated vessel, furthering the imbalance and resulting in a patch
      of non-perfused capillaries next to the dilated 'preferential' shunt vessel.
      Physical principles support or inspire novel hypotheses to explain poorly
      understood phenomena in ophthalmology. This thesis of pericyte death and
      capillary remodelling, which was first proposed by Cogan and Kuwabara, already
      agrees with histological and angiographical observations in diabetic retinopathy.
      We have shown that it is also supported by classical laws of physics.

PMID- 29350689
TI  - Safety of intravitreal injection of ranibizumab in early pregnancy: a series of
      three cases.
AB  - PurposeRanibizumab is used in the treatment of choroidal neovascularization
      (CNV). Although systemic exposure to ranibizumab is low after ocular
      administration, its mechanism of action must be regarded as potentially
      teratogenic and embryo-fetotoxic. Women are advised to wait 3 months after the
      last dose of treatment with ranibizumab before conceiving. Little is known about
      the fetal side-effects of this drug.MethodsThree pregnant women were treated with
      ranibizumab. One patient had idiopathic CNV.ResultsAfter receiving injections at
      10 and 21 weeks after her last menstrual period (LMP), she gave birth to a
      healthy child. The second patient had myopic choroidal neovascularization (mCNV)
      and was treated by a single injection at 17 weeks post LMP. She gave birth to a
      healthy child after an uneventful pregnancy. The third patient had CNV secondary
      to a punctuate inner choroiditis. The injection was performed at 8 weeks post
      LMP. This patient presented a cholestasis of pregnancy at 36 weeks post LMP and
      gave birth at 38 weeks post LMP to a child that did not present any
      malformations.ConclusionsThis case series describes three women who underwent
      intravitreal ranibizumab treatment during pregnancy without showing any
      obstetric, embryofetal or neonatal complications.

PMID- 29350690
TI  - Fluidics and rheology in phaco surgery: what matters and what is the hype?
AB  - Rheology can be defined as the study of materials flow behaviour under applied
      deformation forces (stresses). Inside the eye during cataract surgery, transient
      or reversible deformation (elasticity) and permanent or irreversible deformation
      (flow) can both apply. Although the fluidics of modern phaco machines is an
      important part of this talk, there are a number of issues relating to flow and
      fluids in the eye during cataract surgery, which are unrelated to the machine,
      which can hinder or help the operating surgeon in removing a cataract. In
      addition, coping with the numerous complications, which can occur in the eye at
      the time of surgery, relies on an understanding of how fluidics and rheology can
      help to control the pressurised eye and bring the surgery to a successful
      conclusion.

PMID- 29350691
TI  - A novel mutation (LEU396ARG) in OPA1 is associated with a severe phenotype in a
      large dominant optic atrophy pedigree.

PMID- 29350692
TI  - Control and optimisation of fluid flow in glaucoma drainage device surgery.
AB  - Avoidance of hypotony in the early post-operative phase following glaucoma
      drainage device surgery is paramount, if serious complications are to be avoided.
      Current strategies of preventing early hypotony are either a valve mechanism, as
      those found in Ahmed Glaucoma Valve or flow restrictor as used in Baerveldt or
      Molteno implants. The Ahmed glaucoma valve has a pre-tensioned valve which opens
      and closes at the pre-determined level of intra-ocular pressure. Although the
      opening and closing pressure can be slightly inconsistent, coinciding with the
      change of material used in the plate construction, the reliability appears to
      have improved in recent years. Flow restrictor method, such as vicryl tie and
      Supramid suture stenting, used in non-valved implants utilised the Poissuille's
      equation in predicting the pressure gradient across the tube and thereby avoiding
      the risk of hypotony. Newer generations of glaucoma drainage devices such as Xen,
      Microshunt, and eyeWatch all use the same principle. However, most of these do
      not address the issue of unnecessary residual flow resistance once the bleb
      resistance has formed around the drainage tube or plate except for the EyeWatch
      device.

PMID- 29350693
TI  - Colorectal Cancer: A Collaborative Approach to Improve Education and Screening in
      a Rural Population?.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most commonly diagnosed cancer
      and second leading cause of cancer death for men and women in the United States.
      Although early detection and diagnosis greatly affect survival rates, only about
      half of the U.S. population participates in screening.?. OBJECTIVES: The purpose
      of this project was to implement community-based CRC education and screening.
      Outcomes included CRC knowledge, CRC screening kit return rate, and rate of
      positive screening results. ?. METHODS: Partnering with a community hospital, CRC
      educational sessions and free screening opportunities were provided for 193 local
      city government employees. CRC knowledge was assessed before and after education
      with the Knowledge Assessment Survey. A paired t test indicated significant
      improvement in mean CRC knowledge.?. FINDINGS: More than half of the participants
      elected to take home fecal immunochemical test kits. Of the 29 participants who
      submitted their screening kits for evaluation, eight had positive results and
      received referral recommendations. All participants were notified of their
      screening results. The community-based CRC project was effective in improving CRC
      knowledge and screening participation.

PMID- 29350694
TI  - Collaborative Practice Model: Improving the Delivery of Bad News.
AB  - Ideal bad news delivery requires skilled communication and team support. The
      literature has primarily focused on patient preferences, impact on care
      decisions, healthcare roles, and communication styles, without addressing
      systematic implementation. This article describes how an interdisciplinary team,
      led by advanced practice nurses, developed and implemented a collaborative
      practice model to deliver bad news on a unit that had struggled with
      inconsistencies. Using evidence-based practices, the authors explored current
      processes, role perceptions and expectations, and perceived barriers to
      developing the model, which is now the standard of care and an example of
      interprofessional team collaboration across the healthcare system. This model for
      delivering bad news can be easily adapted to meet the needs of other clinical
      units.?.

PMID- 29350695
TI  - Prechemotherapy Education: Reducing Patient Anxiety Through Nurse-Led Teaching
      Sessions?.
AB  - BACKGROUND: Patients with cancer experience stress surrounding diagnosis and
      treatment. Many cancer centers employ a nurse-led education session to alleviate
      patient anxiety and confusion.?. OBJECTIVES: The goal was to evaluate the effect
      of a nurse-led chemotherapy teaching session on patients' knowledge, anxiety, and
      preparedness for ?cancer-directed therapy.?. METHODS: After discussing treatment
      with their oncologist, participants completed a survey assessing their perceived
      understanding of various treatment topics. After, they underwent a teaching
      session with an oncology nurse. The survey was readministered when patients
      returned for their first and second treatment cycles.?. FINDINGS: Significant
      increases were observed in patients' understanding of their treatment schedule,
      potential adverse effects, and antiemetic medication regimen by the first cycle
      of therapy and a reduction in treatment-related anxiety by the second cycle of
      therapy.

PMID- 29350696
TI  - Cancer Anorexia and Cachexia: Screening in an Ambulatory Infusion Service and
      Nutrition Consultation?.
AB  - BACKGROUND: Cancer anorexia-cachexia syndrome compromises physical function and
      nutritional and emotional well-being. Systematic screening followed by nutrition
      referral for appropriate interventions is rare.?. OBJECTIVES: The purpose of this
      study was to pilot a screening process followed by nutritional assessment and
      intervention when warranted for patients with lung malignancies.?. METHODS: Adult
      patients with lung malignancies were invited to complete the 12-item
      Anorexia/Cachexia Scale (A/CS-12) on the day of chemotherapy initiation in
      ambulatory infusion. Those who scored at a preset threshold were referred to
      nutrition services for a comprehensive assessment and intervention plan. Those
      who scored better than the threshold completed the A/CS-12 at each infusion visit
      for as many as 16 weeks. ?. FINDINGS: 90 participants enrolled, and 46 scored in
      a moderate-to-severe-risk category; of those, 42 were referred to nutrition
      services.

PMID- 29350697
TI  - Antithrombotic Therapy: Evaluation of the Safety of Performing Core Needle Biopsy
      of the Breast Without Suspending Medication?.
AB  - BACKGROUND: Patients are increasingly presenting for outpatient breast biopsy
      while taking medically necessary antithrombotic therapy. Cessation of this
      medication prior to biopsy increases patients' risk of vascular complications. ?.
      OBJECTIVES: This article evaluates the safety of performing core needle biopsies
      of the breast in patients without suspending prescription antithrombotic therapy.
      ?. METHODS: In this retrospective chart review study, patients continued
      prescription antithrombotic therapy prior to and including the day of biopsy.
      Follow-up telephone assessment, relying on patient self-report, was completed on
      the same or next business day. The chart review included report of bleeding as a
      postprocedure complication.?. FINDINGS: None of the 42 women who completed core
      needle biopsy of the breast while on antithrombotic therapy reported
      postdischarge bleeding, and 2 reported hematoma, supporting the safety of
      continuing antithrombotic therapy in patients who undergo core needle biopsy of
      the breast.

PMID- 29350698
TI  - Identification and Management: Sinusoidal Obstruction Syndrome/Veno-Occlusive
      Disease Eelated to Hematopoietic Stem Cell Transplantation?.
AB  - BACKGROUND: Sinusoidal obstruction syndrome (SOS), also called hepatic veno
      occlusive disease (VOD), is a potentially life-threatening complication of
      hematopoietic stem cell transplantation (HSCT) that affects about 1 in 7 patients
      undergoing this procedure. SOS/VOD is caused by the conditioning regimens
      administered prior to HSCT; in some cases, SOS/VOD results from chemotherapy
      alone. SOS/VOD usually develops within three weeks following HSCT; however, it
      can have later onset. ?. OBJECTIVES: Clearly understanding how SOS/VOD develops
      may support prompt detection and treatment when the condition arises.?. METHODS:
      Research on identification and management of SOS/VOD is summarized, and data from
      clinical trials are reviewed.?. FINDINGS: This article describes the syndrome,
      risk factors, signs and symptoms, and appropriate supportive care and treatment.
      The authors also offer some practical tips for detecting SOS/VOD and providing
      patient care, as well as the latest information on treating and preventing this
      condition.

PMID- 29350699
TI  - Medical Cannabis: The Oncology Nurse's Role in Patient Education About the
      Effects of Marijuana on Cancer Palliation?.
AB  - BACKGROUND: Cannabis, also known as marijuana, is legal either medicinally or
      recreationally in 29 states and the District of Columbia, with a majority of the
      U.S. adult population now living in states where cannabis is legal for medicinal
      use. As an advocate for patient autonomy and informed choice, the oncology nurse
      has an ethical responsibility to educate patients about and support their use of
      cannabis for palliation.?. OBJECTIVES: This article aims to discuss the human
      endocannabinoid system as a basis for better understanding the palliative and
      curative nature of cannabis as a medicine, as well as review cannabis delivery
      methods and the emerging role of the oncology nurse in this realm.?. METHODS:
      This article examines the literature and uses a theoretical-conceptual method to
      explore the oncology nurse's role in supporting the use of medicinal cannabis by
      patients with cancer. ?. FINDINGS: The oncology nurse can play a pivotal role in
      supporting patients' use of cannabis for palliation.

PMID- 29350700
TI  - As a New Nurse Myself, How Can I Become a Mentor to New Nurse Colleagues?
AB  - I recently earned my baccalaureate nursing degree and passed the nursing boards.
      Soon, I hope to practice as a clinical oncology nurse. As a new RN, I frequently
      reflect on the people and situations that have influenced my growth so far as a
      nurse. I have been fortunate to work with many clinical mentors who have been
      pivotal in this regard. I realize that many small gestures from my mentors have
      been instrumental in helping me develop my competencies and build my confidence
      in practice. ?.

PMID- 29350701
TI  - Genetic Testing: How Genetics and Genomics Can Affect Healthcare Disparities?.
AB  - Advances in oncology care have transformed treatment approaches as genetics and
      genomics analyses promote implementation of personalized medicine. Genetics and
      genomics research in TP53 have demonstrated that some mutations are prevalent in
      minority populations. This has implications on personalized treatment approaches,
      particularly in early disease stages. The purpose of this article is to describe
      oncology nurses' role in applying these findings in practice to reduce
      disparities observed in cancer and survivorship care.?.

PMID- 29350702
TI  - Focus on Communities.
AB  - The opportunity for oncology nursing to have a broader influence in clinical care
      has never been more in sync with the times, buoyed by breakthroughs in
      diagnostics, precision treatments, and broader applications of interprofessional
      care. However, that influence is still encumbered by inequities in cancer care
      delivery to marginalized or underserved patients here in the United States and
      globally.

PMID- 29350703
TI  - Cancer Prevention and Detection: Application Across the Cancer Trajectory?.
AB  - Oncology nurses have many opportunities to implement cancer prevention and early
      detection recommendations across the cancer trajectory. Understanding the
      principles that guide the recommendations is important to providing comprehensive
      oncology care; many readily available resources can assist oncology nurses with
      this education. Guidelines for the prevention and early detection of malignancy
      are based on a comprehensive cancer risk assessment that includes past medical
      history, lifestyle factors, family history, and, in some cases, genetic testing.
      ?.

PMID- 29350704
TI  - Caregiver Cafe: Providing Education and Support to Family Caregivers of Patients
      With Cancer?.
AB  - BACKGROUND: The many burdens faced by caregivers of patients with cancer are well
      documented. Caregivers are asked to perform procedures, make assessments,
      coordinate care, and communicate with healthcare providers at an increasingly
      complex level. A caregiver quality improvement project, in the form of a
      Caregiver Cafe, was instituted at a National Cancer Institute-designated
      comprehensive cancer center.?. OBJECTIVES: The objectives of the cafe are to (a)
      provide respite and a place for caregivers to relax and be nurtured, (b) provide
      a place for caregivers to meet and support each other, (c) provide answers to
      caregiver questions, and (d) recommend appropriate caregiver resources.?.
      METHODS: The weekly Caregiver Cafe is led by an advanced practice nurse, and the
      format varies depending on the needs of the caregivers who attend.?. FINDINGS:
      Caregivers have verbalized the importance of the cafe in helping them cope with
      their loved ones' cancers and treatments, and many attend on a regular basis. The
      Caregiver Cafe provides support and information and a place to get away from it
      all.

PMID- 29350705
TI  - Direct-to-Consumer Genetic Testing: Helping Patients Make Informed Choices?.
AB  - Using direct-to-consumer genetic testing (DTCGT), individuals can order a genetic
      test, collect and submit a saliva sample, and obtain results about their genetic
      risk for a variety of traits and health conditions without involving a healthcare
      provider. Potential benefits of DTCGT include personal control over genetic
      information and health management decisions, whereas potential risks include
      misinterpretation of results, psychosocial distress, and lack of informed
      consent. Oncology nurses can provide education, support, and advocacy to enable
      patients to truly understand the positives and negatives associated with DTCGT.?.

PMID- 29350707
TI  - Symptom Self-Management: Strategies Used by Older Adults Receiving Treatment for
      Cancer?.
AB  - BACKGROUND: Older adults are at high risk for cancer treatment-related symptoms
      but often accept them as inevitable. This may have a negative impact on patient
      outcomes.?. OBJECTIVES: The purpose of this study is to examine symptom self
      management strategies used by older adults receiving cancer treatment, determine
      the effectiveness of these strategies, and examine relationships between symptom
      self-management and demographic and treatment characteristics.?. METHODS: 100
      adults aged 65 years or older from a community cancer center participated in this
      descriptive, exploratory study. Demographic, treatment, and self-management data
      were collected using an investigator-developed tool. Symptom presence was
      collected using part 1 of the Symptom Representation Questionnaire.?. FINDINGS:
      Participants reported an average of 7.15 symptoms and 3.36 self-management
      strategies used at home. Taste changes were managed most, followed by fatigue and
      bowel changes. On average, strategies used to manage symptoms were moderately
      effective.

PMID- 29350706
TI  - Symptom Burden and Self-Advocacy: Exploring the Relationship Among Female Cancer
      Survivors?.
AB  - BACKGROUND: Although patient self-advocacy is a critical component of patient
      centered care, the association between symptom burden and self-?advocacy has
      received little attention. ?. OBJECTIVES: This analysis evaluates the degree to
      which self-advocacy is associated with symptom burden among women with a history
      of cancer. ?. METHODS: Participants completed online or paper questionnaires.
      Descriptive statistics and ordinary least squares regression models were used to
      analyze the association between the three dimensions of self-advocacy and two
      dimensions of symptom burden. FINDINGS: Participants reported moderate levels of
      symptom burden. Fatigue, disturbed sleep, and memory problems were most common.
      Informed decision making was positively associated with symptom burden and
      participants' burden across the three most severe symptoms. Effective
      communication was negatively associated with total symptom burden and the degree
      to which symptoms interfered with daily life.

PMID- 29350708
TI  - Sleep-Wake Disturbance: A Systematic Review of Evidence-Based Interventions for
      Management in Patients With Cancer.
AB  - BACKGROUND: New or worsening sleep-wake disturbance (SWD) can occur throughout
      the cancer trajectory.?. OBJECTIVES: The purpose of this article is to critically
      review available empirical evidence supporting the efficacy of interventions for
      SWD, highlighting new evidence since the 2006 and 2009 Putting Evidence Into
      Practice (PEP) SWD publications.?. METHODS: A systematic review of studies
      published from 2009-2017 was conducted to identify effective interventions for
      cancer-related SWD. The PEP weight of evidence classification schema was used to
      categorize the strength of evidence.?. FINDINGS: Cognitive behavioral
      intervention/approach is the only intervention that is recommended for practice.
      Mindfulness-based stress reduction and exercise interventions are likely to be
      effective but require more evidence. Pharmacologic interventions, relaxation,
      imagery, meditation, acupuncture, yoga, massage, and psychoeducation have
      insufficient evidence.

PMID- 29350709
TI  - Pricks of Conscience: A Needle-Phobic Patient's Experience of Compassionate
      Nursing Care ?.
AB  - An oncology nurse's warmth, humor, and compassionate care have helped even the
      odds in my wife's decade-long battle with incurable cancer. Needle phobia and a
      complex chemotherapy regimen have made for a challenging course of treatment.
      However, working closely with us, my wife's care team has given us back the
      control that can so easily ebb with remission and relapse. ?.

PMID- 29350710
TI  - Exercise Intervention: Attrition, Compliance, Adherence, and Progression
      Following Hematopoietic Stem Cell Transplantation?.
AB  - BACKGROUND: Exercise is widely touted as an effective intervention to optimize
      health and well-being after high-dose chemotherapy and hematopoietic stem cell
      transplantation. ?. OBJECTIVES: This article reports attrition, compliance,
      adherence, and progression from the strength training arm of the single-blind
      randomized, controlled trial Strength Training to Enhance Early Recovery (STEER).
      ?. METHODS: 37 patients were randomized to the intervention and participated in a
      structured strength training program introduced during hospitalization and
      continued for six weeks after release. Research staff and patients maintained
      exercise logs to document compliance, adherence, and progression. ?. FINDINGS: No
      patients left the study because of burden. Patients were compliant with
      completion of exercise sessions, and their adherence was high; they also
      progressed on their exercise prescription. Because STEER balances intervention
      effectiveness with patient burden, the findings support the likelihood of
      successful translation into clinical practice.

PMID- 29350711
TI  - Precision Coordination: The Growing Role of the Nurse Coordinator in the Era of
      Personalized Medicine?.
AB  - Personalized medicine is expected to positively change the treatment of cancer,
      but early identification of patients who are most likely to benefit requires an
      integrated effort from interprofessional care providers. Centering care around a
      patient's needs is the main task for a nurse coordinator, who is considered the
      core person for communication among all interprofessional care providers. This
      article describes a perspective on the nurse coordinator role as implemented in
      the lung cancer clinic at King Abdulaziz Medical City in Riyadh, Saudi Arabia.?.

PMID- 29350712
TI  - Vaccination for Human Papillomavirus: Immunization Practices in the U.S. Military
AB  - Human papillomavirus (HPV) is the most common sexually transmitted infection and
      is a leading etiology for cancer. The Advisory Committee on Immunization
      Practices (ACIP) recommends routine vaccination of males and females aged 11-26
      years. Studies suggest that U.S. military service members have higher HPV
      incidence rates and lower vaccination rates compared to the national average.
      Although the U.S. military enforces many recommended vaccines, the HPV vaccine
      fails to make the list.

PMID- 29350713
TI  - Hyponatremia and SIADH: A Case Study for Nursing Consideration.
AB  - The leading cause of hyponatremia in patients with cancer is syndrome of
      inappropriate antidiuretic hormone secretion (SIADH); this oncologic emergency
      requires immediate intervention. Left untreated, it can result in increased
      mortality and morbidity. A sodium level less than 135 meq/L is an electrolyte
      irregularity and defined as hyponatremia. It is extremely critical that oncology
      nurses are knowledgeable and able to evaluate and determine when patients are in
      fluid and electrolyte crisis. Nurses should be aware of the specific cancers and
      treatments that put patients at risk for developing hyponatremia. This article
      presents a case study for nursing consideration.

PMID- 29350714
TI  - Health Literacy: Exploring Nursing Challenges to Providing Support and
      Understanding
AB  - BACKGROUND: As patient advocates, oncology nurses must attend to varying levels
      of health literacy among patients and families. However, little is known about
      nurses' experiences and comfort with health literacy assessment and providing
      health literacy support.?. OBJECTIVES: The purpose of this study is to explore
      nurse communication and patient health literacy.?. METHODS: A cross-sectional
      survey design (N = 74) was used to explore nurse communication challenges with
      low-literacy patients and to measure nurses' frequency of assisting with patient
      literacy needs, perceived degree of difficulty communicating with low-literacy
      populations, and perceived comfort with health literacy support.?. FINDINGS: A
      majority of the nurses reported communication challenges with patients who spoke
      English as a second language. Oncology nurses did not identify patient
      communication behaviors that indicated low health literacy. Nurses were least
      comfortable identifying low-literacy patients and assessing a patient's health
      literacy level. More experienced nurses reported more difficulty with low
      literacy populations than less experienced nurses. Providing health literacy
      support to patients should be a core nursing skill.

PMID- 29350715
TI  - Simulation of KTP Laser-Based Zenker Diverticulotomy with a Porcine Model and
      Laryngeal Dissection Station.
AB  - Zenker's diverticulum is a rare cause of progressive dysphagia that is treated
      surgically. KTP laser-based diverticulotomy is one effective treatment.
      Developing a simulation model is helpful for rare conditions. Pigs have a natural
      hypopharyngeal pouch similar to a diverticulum. We present a model for performing
      rigid endoscopic KTP laser diverticulotomy in a porcine model using a laryngeal
      dissection station. Eleven pigs were examined to confirm presence of the
      hypopharyngeal pouch. A specimen was mounted on the modified laryngeal dissection
      station and a KTP laser-based diverticulotomy was performed. Novel aspects
      include use of the laryngeal dissection station and application of the model for
      simulating rigid endoscopic KTP laser diverticulotomy. This model allows trainees
      to practice equipment setup, positioning of the laryngoscope to isolate the
      cricopharyngeal bar, tissue handling, laser safety techniques, and use of the KTP
      laser through the laryngoscope under microscopic visualization.

PMID- 29350716
TI  - Three-dimensional multiscale fiber matrices: development and characterization for
      increased HepG2 functional maintenance for bio-artificial liver application.
AB  - The development of a cell-growth substrate that provides a nature-like
      microenvironment, promotes cell adhesion, and maintains the cells' functional
      activities is a research focus in the field of tissue engineering. In the present
      study, three-dimensional micro-nano multiscale fiber-based substrates were
      developed by depositing biocompatible polycaprolactone (PCL)/PCL-Chitosan (C)/PCL
      C-Gelatin (G) electrospun nanofibers (NFs) on the outer surface of hollow fiber
      membranes (HFMs) in one step. A comparison study with regard to physico-chemical
      characterization, hemocompatibility, cytotoxicity, and cellular functionality was
      performed with the developed matrices. The PCL-C-G NFs-deposited HFMs-based
      matrix showed superior hemocompatibility for blood-contact applications. The
      cytotoxicity of these matrices was found to be minimal. HepG2 cells exhibited an
      exceptionally robust adherence and proliferated growth on the matrix with the
      formation of characteristic multi-cellular spheroids. Furthermore, cell
      functional activities such as albumin secretion, urea synthesis, and cytochrome
      P450 specific activity were measured for the developed matrices. The developed
      three-dimensional multiscale fibers-based matrix can be a potential membrane for
      bioreactor and bio-artificial liver applications.

PMID- 29350717
TI  - Fluoride-ion-binding promoted photoinduced charge separation in a self-assembled
      C60 alkyl cation bound bis-crown ether-oxoporphyrinogen supramolecule.
AB  - A bis-crown ether-oxoporphyrinogen was newly synthesized and self-assembled
      concurrently with C60 alkyl ammonium cations at the crown ether sites and F-
      anions (through hydrogen bonding) at the oxoporphyrinogen core. Ultrafast
      photoinduced charge transfer processes within the donor-acceptor conjugate were
      promoted by fluoride ion binding and this was established using various
      spectroscopic methods and transient absorption studies.

PMID- 29350718
TI  - Energy-efficient electrolytic hydrogen production assisted by coupling urea
      oxidation with a pH-gradient concentration cell.
AB  - An unprecedented asymmetric-electrolyte electrolyzer is proposed using an acidic
      cathode for the hydrogen evolution reaction (HER) and an alkaline anode for the
      urea oxidation reaction (UOR), which significantly decreases the electrical
      energy required for electrolytic hydrogen production.

PMID- 29350719
TI  - Ordered WO3-x nanorods: facile synthesis and their electrochemical properties for
      aluminum-ion batteries.
AB  - In this work, we have synthesized ordered WO3 nanorods via a facile hydrothermal
      process. And the series WO3-x nanorods with oxygen vacancies are obtained via a
      subsequent thermal reduction process. The formation mechanisms of WO3-x nanorods
      with different oxygen vacancies are proposed. And the electrochemical results
      reveal that the WO3-x nanorods exhibit the improved specific capacity due to the
      oxygen vacancies caused by the thermal reduction. More importantly, the reaction
      mechanism of the WO3-x nanorods as cathodes for aluminum-ion batteries has been
      proved.

PMID- 29350721
TI  - Complex molecular systems: a frontier of molecular science.

PMID- 29350722
TI  - Chemical decontamination of iPS cell-derived neural cell mixtures.
AB  - This report describes the design and evaluation of phosphorylated 7-ethyl-10
      hydroxycamptothecin (SN38-P), which selectively eliminates tumor-forming
      proliferative stem cells, including human induced pluripotent stem cells (hiPSCs)
      and neural stem cells, from iPSC-derived neural cell mixtures. Results of the
      present study demonstrate that simple phosphorylation of an anticancer drug can
      provide a safe, cost-effective, and chemically-defined tool for decontaminating
      hiPSC-derived neuron.

PMID- 29350723
TI  - Hot off the press.
AB  - A personal selection of 32 recent papers is presented covering various aspects of
      current developments in bioorganic chemistry and novel natural products such as
      illisimonin A from Illicium simonsii.

PMID- 29350724
TI  - Effects of point defects on the magnetoelectronic structures of MXenes from first
      principles.
AB  - "MXene", a new class of two dimensional materials, has attracted considerable
      research interest due to its unusual chemical bonding pattern as well as
      promising technological applications. Like other 2D materials, very recently,
      these classes of materials were also found to be prone to structural defects,
      thus altering the electronic and transport properties of the host. Using
      extensive first-principles based simulations, we investigated the structural and
      magnetoelectronic (i.e., magnetic and electronic) behaviour of the most probable
      point defects in these MXene systems, such as single vacancies and Schottky type
      double vacancies. Defect formation energies appeared to be strongly dependent
      upon local chemical bonding and the nature of reconstruction. Moreover, this
      layered material exhibited prominent metal to semiconductor or semiconductor to
      metal transition depending upon the type of the system or the defect. Moreover, a
      few of the defective MXenes become magnetic in nature due to the presence of
      unpaired electrons in the spin split d-orbitals. Thus, it is evident that
      intrinsic point defects in MXene can emerge as a potential tool to modulate the
      properties of 2D layered MXenes towards promising device applications.

PMID- 29350725
TI  - Effects of chemically heterogeneous nanoparticles on polymer dynamics: insights
      from molecular dynamics simulations.
AB  - The dispersion of solid nanoparticles within polymeric materials is widely used
      to enhance their performance. Many scientific and technological aspects of the
      resulting polymer nanocomposites have been studied, but the role of the
      structural and chemical heterogeneity of the nanoparticles has just started to be
      appreciated. For example, simulations of polymer films on planar heterogeneous
      surfaces revealed unexpected, non-monotonic activation energy to diffusion on
      varying the surface composition. Motivated by these intriguing results, here we
      simulate via molecular dynamics a different, fully three-dimensional system, in
      which the heterogeneous nanoparticles are incorporated in a polymer melt. The
      nanoparticles are roughly spherical assemblies of strongly and weakly attractive
      sites, in fractions of f and 1 - f, respectively. We show that the polymer
      diffusion is still characterized by a non-monotonic dependence of the activation
      energy on f. The comparison with the case of homogeneous nanoparticles clarifies
      that the effect of the heterogeneity increases on approaching the polymer glass
      transition.

PMID- 29350726
TI  - 3D assembly of Ti3C2-MXene directed by water/oil interfaces.
AB  - MXene is an emerging class of 2D materials exfoliated from ternary carbide and
      nitride ceramics. The exfoliation process, which is an acid etching approach,
      functionalizes the MXene surface with -OH, -O and -F groups. These functional
      groups offer significant opportunities for tuning the colloidal properties of the
      MXene nanoblocks; importantly, this tunability points the way towards a facile
      route for assembling these nanoblocks into 3D architectures that are in demand
      for many applications. This route, presented for the first time here, uses
      water/oil interfaces for assembling Ti3C2-MXene in 3D architectures. It shows
      that cetyl trimethylammonium bromide (CTAB) can be used to tune the hydrophilic
      hydrophobic balance of Ti3C2-MXene via the interaction of positively charged 
      N(CH3)3 and -O groups on the MXene surface. Crucially, it is found that this
      interaction can be controlled via the hydrogen ion concentration in the aqueous
      phase. Stable oil-in-water emulsions are the only product when the aqueous phase
      is neutral or basic. This understanding led us to fabricate a high internal phase
      Pickering emulsion with more than 70 vol% oil droplets and also a solid porous
      monolith based on this emulsion template.

PMID- 29350727
TI  - 'One-pot' sequential enzymatic modification of synthetic glycolipids in vesicle
      membranes.
AB  - beta(1,4)-Galactosyltransferase (beta4Gal-T1) and T. cruzi trans-sialidase (TcTS)
      have been used in a 'one-pot' cascade to provide vesicles (liposomes) with a
      trisaccharide coating. These soluble enzymes catalysed the transfer of galactose
      then sialic acid onto a synthetic N-acetylglucolipid embedded in the bilayers.
      Clustering of this substrate into microdomains increased the rate of sialylated
      lipid production, showing that an increase in beta4Gal-T1 activity is carried
      through the enzymatic cascade. These coatings modulated cell recognition.
      Hepatocellular carcinoma cells took up vesicles modified by beta4Gal-T1 alone
      more extensively than sialylated vesicles produced by 'one-pot' sequential
      enzymatic modification.

PMID- 29350729
TI  - In situ mechanical resonance behaviour of pristine and defective zinc blende GaAs
      nanowires.
AB  - The structural versatility of semiconducting gallium arsenide (GaAs) nanowires
      (NWs) provides an exciting direction for the engineering of their mechanical and
      dynamic properties. However, the dynamic behaviour of GaAs NWs remains
      unexplored. In this study, comprehensive in situ mechanical resonance tests were
      conducted to explore the dynamic behaviour of pristine and defective zinc blende
      GaAs NWs. The effects of stacking faults (SFs), amorphous shell, NW tapering and
      end-mass particles were investigated. The quality factors (QFs) of the GaAs NWs
      were found to be predominately governed by surface effects, which increased
      linearly with the volume to surface area ratio. Interestingly, SFs were found not
      to influence the QFs. To extract the mechanical properties, the Euler-Bernoulli
      beam theory was modified, to incorporate the core-shell model, NW tapering and
      end-mass particles. It was found that the core-shell model accurately predicts
      the mechanical properties of the pristine GaAs NWs, which exhibit significant
      stiffening at radii below 50 nm. Conversely, the mechanical properties of the
      defective NWs were influenced by the presence of SFs, causing a wide variance in
      the Young's modulus. Apart from establishing an understanding of the resonance
      behaviour of GaAs NWs, this research provides guidance for the design of NWs for
      their applications in dynamic nanomechanical devices with tailorable dynamic
      properties.

PMID- 29350728
TI  - Dual chain extension effect and antibacterial properties of biomolecules
      interleaved within LDH dispersed into PBS by in situ polymerization.
AB  - Nanocomposites based on poly(butylene succinate) (PBS) and hydrotalcite-type
      anionic clays (HTs) organo-modified with biomolecules characterized by
      antibacterial and/or antioxidant activities, such as l-ascorbic acid (ASA),
      phloretic acid (HPP), l-tyrosine (TYR) and l-tryptophan (TRP), have been prepared
      by in situ polymerization. From XRD analysis and rheology experiments in a molten
      polymer state, intercalated HT hybrid platelets acting here as a hybrid filler
      are found to be well dispersed into polymers while providing a chain extension
      effect on PBS. Moreover, the molecules, when hosted within a HT interlayer gap,
      do preserve their pristine antibacterial activity, both in HT and in the
      resulting PBS composites. In particular, under the experimental conditions
      tested, HT/ASA and HT/TYR present the best combination of both properties (chain
      extension effect and antibacterial), especially versus E. coli as high as 90 and
      97% of inhibition, respectively, using 2.5 wt% hybrid filler only. These findings
      open future applications for PBS associated with the hybrid HT filler as
      multifunctional materials in active packaging applications.

PMID- 29350730
TI  - Three dimensional porous SiC for lithium polysulfide trapping.
AB  - One of the key issues in lithium sulfur batteries is the fast capacity fade
      induced by the lithium polysulfide (LiPS) migration. Hence, a series of three
      dimensional (3D) porous SiC materials with active sp2 Si atoms have been designed
      for lithium polysulfide entrapping in Li-S batteries. The ZGM-SiC-1 and AGM-SiC-3
      have been confirmed to be thermodynamically and dynamically stable from the
      formation energy and phonon dispersion spectrum, meanwhile showing good
      mechanical properties. The moderate band gaps suggest fast electron transport
      during the charge-discharge cycles of the Li-S batteries, especially in ZGM-SiC
      1. The 3D porous ZGM-SiC-1 and AGM-SiC-3 display strong affinity to S8 and LiPS
      with the direct Si-S and Li-C interactions, which are comparable to the case of
      the N doped carbon host. As compared to the 3D pristine graphene monoliths and
      two dimensional SiC nanosheet, the entrapping of LiPS in the 3D porous SiC host
      is much stronger (ca. 2.5 eV to 3.5 eV), which is effective in inhibiting the
      shutter effect in Li-S batteries. Most interestingly, the extraordinarily strong
      adsorption of the S8 molecule indicates high sulfur loading in the 3D porous SiC
      host.

PMID- 29350731
TI  - The oxidation of sulfur(iv) by reaction with iron(iii): a critical review and
      data analysis.
AB  - The dependences on ionic strength of the hydrolysis constants of Fe3+ and of the
      first dissociation constant of sulfurous acid are briefly reviewed. The data are
      needed to derive from apparent stability constants reported in the literature the
      stability constants for the three iron-sulfito complexes defined by the
      equilibria (c1) FeOH2+ + HSO3- = FeSO3+ + H2O, (c2) FeSO3+ + HSO3- = Fe(SO3)2- +
      H+, (c3a) Fe(SO3)2- + HSO3- = Fe(SO3)3H2-, where Kc1 = 1982 +/- 518 dm3 mol-1,
      Kc2 = 0.72 +/- 0.08, Kc3a = 189 +/- 9 dm3 mol-1 (ionic strength MU = 0.1 mol dm
      3). The rapid formation of these complexes is followed by a slower decomposition
      leading to the formation of SO3- radicals; the associated rate coefficients are
      k1 = 0.19 s-1, k1a ~ 0.04 s-1, and k1b ~ 0.08 s-1, respectively. The subsequent
      reaction leads to dithionate and sulfate as products. Overall rates and product
      yields from a variety of studies of the slow reaction are found to be consistent
      with a mechanism, in which the production of dithionate occurs mainly by the
      reaction of SO3- with FeSO3+ and that of sulfate by the reaction of SO3- with
      FeOH2+ and/or Fe3+. The role of copper as a catalyst is also analyzed. Rate
      coefficients for individual reactions are estimated from the data at low pH (MU =
      1.0 mol dm-3) under conditions where the 1 : 1-complex is prevalent. They are
      extrapolated to lower ionic strengths for an analysis of the data obtained at
      higher pH to explore conditions when reactions of the higher complexes become
      important. The overall rate and the product yields of the reaction depend
      critically on the pH, the initial ratio of S(iv) to Fe(iii) and the ionic
      strength of the solution.

PMID- 29350732
TI  - Complete amplitude and phase control of light using broadband holographic
      metasurfaces.
AB  - Reconstruction of light profiles with amplitude and phase information, called
      holography, is an attractive optical technology with various significant
      applications such as three-dimensional imaging and optical data storage.
      Subwavelength spatial control of both amplitude and phase of light is an
      essential requirement for an ideal hologram. However, traditional holographic
      devices suffer from their restricted capabilities of incomplete modulation in
      both amplitude and phase of visible light; this results in sacrifice of optical
      information and undesirable occurrences of critical noises in holographic images.
      Herein, we have proposed a novel metasurface that is capable of completely
      controlling both the amplitude and phase profiles of visible light independently
      with subwavelength spatial resolution. The full, continuous, and broadband
      control of both amplitude and phase was achieved using X-shaped meta-atoms based
      on the expanded concept of the Pancharatnam-Berry phase. The first experimental
      demonstrations of the complete complex-amplitude holograms with subwavelength
      definition at visible wavelengths were achieved, and excellent performances with
      a remarkable signal-to-noise ratio as compared to those of traditional phase-only
      holograms were obtained. Extraordinary control capability with versatile
      advantages of our metasurface paves a way to an ideal holography, which is
      expected to be a significant advancement in the field of optical holography and
      metasurfaces.

PMID- 29350733
TI  - A catalyst-free intermolecular trans-iodoalkylation of alkynes.
AB  - We report the first catalyst-free and trans-selective iodoalkylation reaction of
      alkynes with a series of alpha-carbonyl compounds. This unprecedented three
      component iodoalkylation reaction is enabled by using
      (iodoethynyl)trimethylsilane as a radical initiator and iodide source. The 1,2
      difunctionalization affords alkenyl iodides, which are versatile building blocks
      for the construction of tri-substituted alkene derivatives.

PMID- 29350734
TI  - A nearly perfect spin filter and a spin logic gate based on a porphyrin/graphene
      hybrid material.
AB  - Although a lot of theoretical studies have designed perfect spin filters using
      inorganic/organic/organometallic materials, their fabrication methods are not
      experimentally feasible. This dilemma could be solved by a recent experiment,
      where porphyrins have been covalently coupled to graphene edges in a precise
      manner (Y. He et al., Nat. Chem., 2017, 9, 33-38). In particular, experimental
      results confirmed that the intrinsic features of porphyrins for metallation are
      preserved after dehydrogenative coupling to graphene edges, paving the way for
      realizing synthesizable spintronic devices. Inspired by this work, we report new
      M-porphyrin/graphene (M = Cr, Mn, Fe, and Co) hybrid systems with tunable
      functionalities on the basis of nonequilibrium Green's functions in combination
      with density functional theory. The Mn-porphyrin/graphene hybrid system exhibits
      an extremely high spin polarization coefficient in a parallel magnetic
      configuration. Our results also confirm that the magnetic configuration plays an
      important role in realizing a high-performance spin filter. The interesting spin
      transport properties in the parallel and antiparallel magnetic configurations
      also make the hybrid system a suitable candidate for realizing the AND logic
      operation.

PMID- 29350740
TI  - Full-dimensional analytical potential energy surface describing the gas-phase Cl
      + C2H6 reaction and kinetics study of rate constants and kinetic isotope effects.
AB  - Within the Born-Oppenheimer approximation a full-dimensional analytical potential
      energy surface, PES-2017, was developed for the gas-phase hydrogen abstraction
      reaction between the chlorine atom and ethane, which is a nine body system. This
      surface presents a valence-bond/molecular mechanics functional form dependent on
      60 parameters and is fitted to high-level ab initio calculations. This reaction
      presents little exothermicity, -2.30 kcal mol-1, with a low height barrier, 2.44
      kcal mol-1, and intermediate complexes in the entrance and exit channels. We
      found that the energetic description was strongly dependent on the ab initio
      level used and it presented a very flat topology in the entrance channel, which
      represents a theoretical challenge in the fitting process. In general, PES-2017
      reproduces the ab initio information used as input, which is merely a test of
      self-consistency. As a first test of the quality of the PES-2017, a theoretical
      kinetics study was performed in the temperature range 200-1400 K using two
      approaches, i.e. the variational transition-state theory and quasi-classical
      trajectory calculations, with spin-orbit effects. The rate constants show
      reasonable agreement with experiments in the whole temperature range, with the
      largest differences at the lowest temperatures, and this behaviour agrees with
      previous theoretical studies, thus indicating the inherent difficulties in the
      theoretical simulation of the kinetics of the title reaction. Different sources
      of error were analysed, such as the limitations of the PES and theoretical
      methods, recrossing effects, and the tunnelling effect, which is negligible in
      this reaction, and the manner in which the spin-orbit effects were included in
      this non-relativistic study. We found that the variation of spin-orbit coupling
      along the reaction path, and the influence of the reactivity of the excited
      Cl(2P1/2) state, have relative importance, but do not explain the whole
      discrepancy. Finally, the activation energy and the kinetics isotope effects
      reproduce the experimental information.

PMID- 29350741
TI  - Hybrid nanowires and nanoparticles of WO3 in a carbon aerogel for supercapacitor
      applications.
AB  - In the field of electrochemical energy storage, incorporation of metal oxides
      into porous carbon has attracted significant attention. Since each advantage of
      nanoparticles and nanowires of metal oxide has been distinguished for
      supercapacitor applications, a combination of the advantages of both structures
      together can meet a capacitive synergy. In this study, WO3 nanowires and
      nanoparticles were first incorporated into a carbon aerogel (CA) simultaneously
      via a facile and one-pot route. A comparative study on the capacitive properties
      of this novel hybrid structure and single nanoparticles in CA was conducted. The
      introduction of WO3 nanowires with diameter <40 nm provided an additional pair of
      redox peaks and improved the specific capacitance by 50% and the rate capacity by
      61%. The composite within the hybrid nanowires and nanoparticles exhibits an
      excellent cycling stability of only 2% decay in specific capacitance detected at
      50 mV s-1 for 1000 cycles. The individual contribution of nanowires and
      nanoparticles to the enhanced capacitance has been discussed, and the enhanced
      capacitive properties can be ascribed to the hybrid structure better for charge
      transport during the electrochemical process. More importantly, this route can be
      extended to incorporate nanowires of other metal oxides into mesoporous carbon,
      and enhanced capacitive properties can be expected.

PMID- 29350742
TI  - Direct observation of the topological spin configurations mediated by the
      substitution of rare-earth element Y in MnNiGa alloy.
AB  - The evolution of topological magnetic domains microscopically correlates the
      dynamic behavior of memory units in spintronic application. Nanometric bubbles
      with variation of spin configurations have been directly observed in a
      centrosymmetric hexagonal magnet (Mn0.5Ni0.5)65(Ga1-yYy)35 (y = 0.01) using
      Lorentz transmission electron microscopy. Magnetic bubbles instead of biskyrmions
      are generated due to the enhancement of quality factor Q caused by the
      substitution of rare-earth element Y. Furthermore, the bubble density and
      diversified spin configurations are systematically manipulated via combining the
      electric current with perpendicular magnetic fields. The magnetic bubble lattice
      at zero field is achieved after the optimized manipulation.

PMID- 29350743
TI  - Facile preparation of carbon-dot-supported nanoflowers for efficient photothermal
      therapy of cancer cells.
AB  - Herein, novel self-assembled red-emissive C-dots@Au nanoflowers were developed,
      and they demonstrated efficient photothermal properties under 750 nm laser
      irradiation. Moreover, C-dots@Au nanoflowers showed the ability of simultaneous
      photoacoustic and fluorescence imaging. Our study may provide a novel strategy
      for the efficient phototherapy of cancer cells based on C-dots.

PMID- 29350744
TI  - Preventing Mesh Pore Collapse by Designing Mesh Pores With Auxetic Geometries: A
      Comprehensive Evaluation Via Computational Modeling.
AB  - Pelvic organ prolapse (POP) meshes are exposed to predominately tensile loading
      conditions in vivo that can lead to pore collapse by 70-90%, decreasing overall
      porosity and providing a plausible mechanism for the contraction/shrinkage of
      mesh observed following implantation. To prevent pore collapse, we proposed to
      design synthetic meshes with a macrostructure that results in auxetic behavior,
      the pores expand laterally, instead of contracting when loaded. Such behavior can
      be achieved with a range of auxetic structures/geometries. This study utilized
      finite element analysis (FEA) to assess the behavior of mesh models with eight
      auxetic pore geometries subjected to uniaxial loading to evaluate their potential
      to allow for pore expansion while simultaneously providing resistance to tensile
      loading. Overall, substituting auxetic geometries for standard pore geometries
      yielded more pore expansion, but often at the expense of increased model
      elongation, with two of the eight auxetics not able to maintain pore expansion at
      higher levels of tension. Meshes with stable pore geometries that remain open
      with loading will afford the ingrowth of host tissue into the pores and improved
      integration of the mesh. Given the demonstrated ability of auxetic geometries to
      allow for pore size maintenance (and pore expansion), auxetically designed meshes
      have the potential to significantly impact surgical outcomes and decrease the
      likelihood of major mesh-related complications.

PMID- 29350745
TI  - TiO2 nanoparticles can selectively bind CXCL8 impacting on neutrophil chemotaxis.
AB  - The interaction between TiO2 nanoparticles (NPs) and inflammatory cytokines,
      including CXCL8, a clinically relevant pro-inflammatory chemokine was
      investigated. TiO2 is present in tissues adjacent to failing implanted Ti
      (titanium) devices. TiO2 NPs were shown to bind to CXCL8 in vitro, causing
      perturbation of quantification of CXCL8 by ELISA, in both simple and complex
      protein panels, in a dose-dependent manner. Binding between TiO2 NPs and CXCL8
      was demonstrated by protein gel electrophoresis. TiO2 NPs were also shown to
      inactivate the chemoattractant property of CXCL8 in a dose-dependent manner,
      suggesting that the binding between TiO2 NPs and CXCL8 is likely to be clinically
      relevant. The results of this study disputed the applicability of detection of
      CXCL8 by ELISA in systems where TiO2 NPs were present. Clinically, the disruption
      of chemotaxis of neutrophils in response to CXCL8 in the presence of TiO2 might
      mean a hampered immune response to inflammation in tissues containing TiO2 NPs.

PMID- 29350746
TI  - Positive view and increased likely uptake of follow-up testing with analysis of
      cell-free fetal DNA as alternative to invasive testing among Danish pregnant
      women.
AB  - INTRODUCTION: The aim of this study was to investigate the attitude (view, likely
      uptake and preferred strategy) towards cell-free fetal DNA (cfDNA) testing among
      pregnant women before a first-trimester risk assessment for trisomy 21
      (unselected women) and after obtaining a high risk. MATERIAL AND METHODS:
      Unselected and high-risk women attending first-trimester screening
      (Rigshospitalet, Copenhagen University Hospital) were invited to fill out the
      questionnaire Antenatal testing for Down syndrome as an online survey. RESULTS:
      The survey included 203 unselected and 50 high-risk women (response rates of
      74.8% and 84.7%, respectively). Nearly all considered cfDNA testing a positive
      development in antenatal care, and 97.2% would like it to be offered. Offering
      cfDNA testing as an alternative to invasive testing would increase the uptake of
      follow-up testing compared with invasive testing alone (98.8% vs. 90.7%, p <
      0.001). Women who would only accept follow up by cfDNA testing were more likely
      to continue an affected pregnancy (30.0% vs. 3.6%, p < 0.001) or have doubts
      about termination (50.0% vs. 32.1%, p < 0.001). CONCLUSIONS: Offering cfDNA
      testing would likely increase the uptake of follow-up testing without a
      corresponding rise in the termination rate of affected fetuses as some women test
      for information only. However, both unselected and high-risk women had
      overwhelmingly positive views underlining attention to avoid routinization.

PMID- 29350747
TI  - Low semen quality and experiences of masculinity and family building.
AB  - INTRODUCTION: Infertility is a concern for men and women. There is limited
      knowledge on how male factor infertility affects the couple in fertility
      treatment. The aim of this study was to explore how severe male factor
      infertility affects men's sense of masculinity, the couple's relationship and
      intentions about family formation. MATERIAL AND METHODS: Semi-structured
      qualitative interview study at the Fertility Clinic at Copenhagen University
      Hospital, Hvidovre, Denmark. Ten men with very poor semen quality initiating
      fertility treatment were interviewed between November 2014 and May 2015. Data
      were analyzed using qualitative content analysis. RESULTS: Three themes were
      identified: "Threatened masculinity", "Being the strong one: impact on the
      couple" and "Consideration of family building options: a chapter not willing to
      start". The men felt that they could not fulfill their role as a man. Some
      couples had conflicts and discussions because the women in general wanted to talk
      more about infertility than the men. The men focused on having a biological
      child. They wanted to focus on achieving biological parenthood and postpone
      consideration of other family building options such as adoption or the use of
      semen donation in order to become a parent. CONCLUSIONS: The consequence of
      severe male factor infertility was a threatened sense of masculinity. Fertility
      specialists and nurses should recognize the impact of male infertility and create
      space to give their patients an opportunity to verbalize their concerns and
      questions related to male factor infertility and the different challenges that
      the couple faces during the fertility treatment.

PMID- 29350748
TI  - Protective Effect of Chitosan Oligosaccharides Against Cyclophosphamide-Induced
      Immunosuppression and Irradiation Injury in Mice.
AB  - : Chitosan oligosaccharides (COS), hydrolyzed products of chitosan, was found to
      display various biological activities. Herein, we assessed the immunostimulatory
      activity of COS both in in vitro and in vivo studies. In vitro cytotoxicity
      studies to murine macrophage RAW264.7 revealed that COS is safe even at the
      maximum tested concentration of 1000 MUg/mL. It also stimulates the production of
      nitric oxide (NO) and tumor necrosis factor (TNF-alpha) and enhances the
      phagocytosis in COS-stimulated RAW264.7. We have shown that the COS could
      significantly (P < 0.05) restore the reduced immune organs indices, phagocytic
      index, lymphocyte proliferation, natural killer cell activity, and antioxidant
      enzyme activities in a cyclophosphamide-induced immunosuppressed mice model. COS
      can also improve the survival rate in irradiation injury mice and significantly
      (P < 0.05) increased the spleen indices and up-regulates the CD4+/CD8+ ratio in
      splenocytes. In sum, the aforementioned results suggest that COS might has the
      potential to be used as an immunostimulatory agent in patients with immune
      dysfunctions or be a model for functional food development. PRACTICAL
      APPLICATION: COS might has the potential to be used as an immunostimulatory agent
      in patients with immune dysfunctions or be a model for functional food
      development.

PMID- 29350749
TI  - Quality Characteristics of a Low-Fat Beef Patty Enriched by Polyunsaturated Fatty
      Acids and Vitamin D3.
AB  - : Olive and linseed oils have high contents of oleic acid and n-3 fatty acids
      (FA), respectively. Vitamin D3 , an essential nutrient, is in low contents in
      meat. This study investigated the potential application of olive and linseed
      oils' mixture as a backfat replacer, and vitamin D3 as a supplement, in order to
      develop a product enriched by polyunsaturated FAs and vitamin D3 . Two treatments
      were manufactured: conventional (C: 0% emulsion, 0 MUg vitamin D3 /100 g product)
      and modified (M: 10.9% emulsion/, 8.3 MUg vitamin D3 /100 g product). The quality
      characteristics and cooking effects on the FA and vitamin D3 contents were
      assessed. The sensory properties of cooked patties were not affected by olive and
      linseed oils' mixture (P > 0.05). The instrumental textural parameters were lower
      in cooked M patties (P < 0.01), except springiness (P = 0.766) that was not
      affected by formulation. The contents of alpha-linoleic acid in M patty were 19
      fold higher than those from C patty. The contents of n-3 and n-6 were higher in M
      patty (P < 0.05) than in C patty. Although cooking decreased the content of
      vitamin D3 in M patty (6.7 compared with 5.2 MUg/100 g product), considerable
      increments were achieved compared to C patty. PRACTICAL APPLICATION: There is an
      increasing demand of consumers for healthier meat products; therefore, the
      improvement of their nutritional profile without negatively affecting quality
      characteristics is key factor for meat sector. This study emphasizes the
      feasibility of using the combination of olive and linseed oils' mixture and
      vitamin D3 to yield new meat products with high contents of polyunsaturated fatty
      acids and vitamin D3 . The effectiveness of combination of oils mixture and
      vitamin D3 tested in this study is proven and the high contribution of vitamin D3
      and some fatty acids of nutritional interest identified.

PMID- 29350751
TI  - Review of the Comparative Susceptibility of Microbial Species to
      Photoinactivation Using 380-480 nm Violet-Blue Light.
AB  - Antimicrobial violet-blue light is an emerging technology designed for enhanced
      clinical decontamination and treatment applications, due to its safety, efficacy
      and ease of use. This systematized review was designed to compile the current
      knowledge on the antimicrobial efficacy of 380-480 nm light on a range of health
      care and food-related pathogens including vegetative bacteria, bacterial
      endospores, fungi and viruses. Data were compiled from 79 studies, with the
      majority focussing on wavelengths in the region of 405 nm. Analysis indicated
      that Gram-positive and Gram-negative vegetative bacteria are the most susceptible
      organisms, while bacterial endospores, viruses and bacteriophage are the least.
      Evaluation of the dose required for a 1 log10 reduction of key bacteria compared
      to population, irradiance and wavelength indicated that microbial titer and light
      intensity had little effect on the dose of 405 nm light required; however, linear
      analysis indicated organisms exposed to longer wavelengths of violet-blue light
      may require greater doses for inactivation. Additional research is required to
      ensure this technology can be used effectively, including: investigating
      inactivation of multidrug-resistant organisms, fungi, viruses and protozoa;
      further knowledge about the photodynamic inactivation mechanism of action; the
      potential for microbial resistance; and the establishment of a standardized
      exposure methodology.

PMID- 29350750
TI  - The Hepatoprotective Effect of Selenium-Enriched Yeast and Gum Arabic Combination
      on Carbon Tetrachloride-Induced Chronic Liver Injury in Rats.
AB  - : The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY)
      and Gum Arabic (GA) have been reported. This study aimed to determine the
      hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl4 )
      induced chronic liver injury in rats and to explore their synergistic mechanisms
      of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked
      as control, (B) was administered CCl4 , (C-E) were fed daily by GA, SY, and GA+SY
      respectively after mixing with basal diet, following CCl4 -intoxication. GA and
      SY combination significantly ameliorated CCl4 -induced reduction in serum total
      protein with elevation in aspartate transaminase (AST) and alanine transaminase
      (ALT) in addition to restoring the histopathological changes and hepatic content
      of hydroxyproline. GA and SY combination was also effective in reducing lipid
      peroxidation (MDA), consistent with an increase in total antioxidant capacity (T
      AOC), glutathione (GSH), superoxide dismutase (SOD) activities, indicating the
      suppression of liver oxidative stress. Furthermore, liver inflammation was
      ameliorated by GA and SY combination through inhibition of nuclear factor-kappa
      (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2(COX-2),
      monocyte chemotactic protein-1 (MCP-1), and toll-like receptor 4(TLR-4) over
      expression in the liver. Moreover, the up-regulation of proliferating cell
      nuclear antigen (PCNA) expression by GA and SY combination enhanced the
      regeneration of liver tissue after CCl4 -administration. The expression of
      Collagen1, alpha-smooth muscle actin (alpha-SMA), and transforming growth factor
      beta1 (TGFbeta1), was obviously ameliorated by GA and SY combination, suggesting
      the amelioration of profibrotic response of the liver. Taken together, our
      current study suggests that GA and SY combination exhibit a significant
      hepatoprotective activity, which more efficient than GA or SY alone. PRACTICAL
      APPLICATION: Chronic liver diseases are the serious health problems, which
      increase the morbidity and mortality in the world today. Selenium-enriched yeast
      (SY) and Gum Arabic (GA) combination might be potential dietary agents could
      obviously ameliorate chronic liver damage, higher than GA and SY alone. They act
      to suppress the inflammation and inhibit the profibrotic response as well as
      support the liver regeneration.

PMID- 29350752
TI  - Importance of Applying Condiments in a Commonly Consumed Food System for
      Understanding the Association Between Familiarity and Sensory Drivers of Liking:
      A Study Focused on Doenjang.
AB  - : Doenjang, a Korean traditional fermented soybean paste, is one of the most
      essential condiments in Korean cuisine. Condiments are rarely consumed as it is,
      and are generally applied to other foods. The objective of this study was to
      understand how sensory drivers of liking of Doenjang would be affected according
      to food forms in which it is evaluated: the original paste form compared with a
      normally consumed soup form, and to understand the association of familiarity of
      evaluated food form. Descriptive analysis and consumer acceptability test was
      performed in 2 consumption forms: the original paste form and the Doenjang soup
      from. For consumer liking test, elderly consumers who have more experience to
      traditional Deonjang were compared to the young in their response to Doenjang
      paste and soup. The descriptive analysis results showed that the characteristic
      sensory features of the Deonjang samples were little affected based on the food
      system in which it was evaluated. However, when the paste was applied in soup,
      the intensities of the characteristic sensory features were reduced.
      Acceptability and familiarity of traditional type Doenjang samples for the young
      and for the elderly consumers were very similar in paste, but it differed when
      the samples were evaluated in soup. Thus, expectation difference between the
      young and the elderly was better revealed in soup, a more common food form
      consumed in practice. The results of this study indicate the importance of
      understanding sensory drivers of liking for a condiment such as Doenjang in their
      commonly consumed forms. PRACTICAL APPLICATION: Compared to the original
      condiment form, expectation difference between the young and the elderly were
      better revealed in Deonjang soup, a food form normally consumed in practice.
      Thus, the results of this study reinforced the importance of investigating
      sensory drivers of liking for a condiment in a food form that is normally
      consumed in practice for accurate understanding on consumer preference.

PMID- 29350753
TI  - Impact of relaxation of the one-child policy on maternal mortality in Guangzhou,
      China.
AB  - OBJECTIVE: To assess the impact of the one-child policy in China on maternal
      mortality. METHODS: The present retrospective study included maternal death data
      from Guangdong, China, from January 1, 2006, to December 31, 2015; data from 2013
      were excluded because they were not available. Maternal deaths were divided into
      legal and illegal pregnancies based on adherence to the one-child policy. The
      maternal mortality ratio (MMR) was compared between the groups, temporal trends
      in the MMR were examined, and comparisons were made of the causes of death and
      access to maternity care. RESULTS: The final analysis included 847 520 live
      deliveries and 383 maternal deaths. The MMR among legal pregnancies declined
      moderately from 18.5 deaths per 100 000 live deliveries in 2006 to 12.2 deaths
      per 100 000 live deliveries in 2015 (P=0.029), whereas the MMR among illegal
      pregnancies declined dramatically from 1268.4 deaths per 100 000 live deliveries
      to 177.5 deaths per 100 000 live deliveries (P<0.001). The proportion of
      avoidable maternal deaths decreased and access to quality maternity care improved
      among illegal pregnancies during the study period. CONCLUSIONS: Maternal
      mortality among illegal pregnancies declined with relaxation of the one-child
      policy in China.

PMID- 29350754
TI  - Neurocognitive differences between inpatients and outpatients with
      symptomatically nonremitted schizophrenia: A cross-sectional study.
AB  - PURPOSE: We aimed to examine whether neurocognition in individuals with
      nonremitted schizophrenia differed between inpatients and outpatients. DESIGN AND
      METHODS: We recruited 59 inpatients and 41 patients with nonremitted
      schizophrenia (assessed with the Andreason criteria), and neurocognitive
      functions were compared between both, controlling for demographics, psychiatric
      symptoms. FINDINGS: Outpatients with nonremitted schizophrenia performed better
      on tests of processing speed, visual attention, and working memory than did
      inpatients with nonremitted. PRACTICE IMPLICATIONS: To facilitate discharge for
      nonremitted inpatients, nursing could focus on processing speed, e.g., arranging
      the environment such that patients do not need quick responses.

PMID- 29350755
TI  - Microbial and Chemical Shelf-Life of Vacuum Steam-Pasteurized Whole Flaxseed and
      Milled Flaxseed.
AB  - : Flaxseed is an oilseed with many health benefits. Flaxseed may be consumed raw
      or in processed form. In the raw form, there is a potential for microbial
      contamination. Several pasteurization methods have been used to reduce microbial
      contamination. However, such treatments may affect chemical properties of foods.
      In this study, vacuum steam-pasteurization was conducted on whole flaxseed and
      milled flaxseed using 4 different conditions (3 min at 75  degrees C, 3 min at 90
      degrees C, 9 min at 90  degrees C, and 3 min at 105  degrees C). Microbial and
      chemical shelf-life was monitored for 28 wk (36 wk for aerobic plate counts).
      Significant reduction (P < 0.05) in microbial counts (total aerobic plate counts,
      and yeast and mold counts) occurred after pasteurization and during storage of
      both whole flaxseed and milled flaxseed. Although both the moisture content and
      aw increased after pasteurization, they were similar to the unpasteurized samples
      during storage. Peroxide value, free fatty acid, headspace volatiles, fatty acid
      profiles, oil content, and secoisolariciresinol diglucoside (SDG) content were
      chemical indices measured. Only small changes were observed in the chemical
      indices after vacuum steam-pasteurization for both pasteurized whole flaxseed and
      milled flaxseed as compared to the unpasteurized flaxseed at most instances.
      Vacuum steam-pasteurization can be used as a safe alternative for the microbial
      reduction of low-moisture products, such as flaxseed, without significantly
      affecting chemical stability. PRACTICAL APPLICATION: Vacuum steam-pasteurization
      can be effectively used for the treatment of whole flaxseed and milled flaxseed
      to reduce spoilage microorganisms, such as total aerobes and yeasts and molds. In
      addition, this pasteurization method had minimal effects on several chemical
      shelf-life parameters with positive impact on SDG of the processed flaxseed.

PMID- 29350756
TI  - Cytocompatibility of Biodentine and iRoot FS with human periodontal ligament
      cells: an in vitro study.
AB  - AIM: To evaluate the cytocompatibility of Biodentine and iRoot FS with human
      periodontal ligament cells (hPDLCs). METHODOLOGY: Human periodontal ligament
      cells were characterized by flow cytometry and immunocytochemical analysis. Human
      periodontal ligament cell adhesion was assessed by scanning electron microscopy
      at day 3; proliferation by live/dead assay at days 1, 3 and 7; and osteogenic
      differentiation by alkaline phosphatase (ALP) activity staining, ALP
      quantification analysis and qRT-PCR at days 7 and 14. Data were analysed with
      anova and independent sample t-tests with SPSS 21.0. RESULTS: Both iRoot FS and
      Biodentine increased the adhesion of hPDLCs at day 3. Compared to Biodentine,
      iRoot FS positively increased hPDLC proliferation on days 3 (P = 0.03) and 7 (P =
      0.00). Osteogenic marker ALP was observed consistently in all samples, with iRoot
      FS having significantly higher ALP activity at day 14 (P = 0.00). Compared with
      Biodentine, iRoot FS significantly increased the mRNA level of ALP, COL1 and
      Runx2, and OCN increased only on day 14 (P < 0.05). CONCLUSIONS: iRoot FS had a
      positive effect on the adhesion, proliferation and biomineralization of hPDLCs
      compared with Biodentine.

PMID- 29350757
TI  - Hepatoprotective Effects of Sophoricoside against Fructose-Induced Liver Injury
      via Regulating Lipid Metabolism, Oxidation, and Inflammation in Mice.
AB  - : The dried fruit of Sophora japonica L. is a traditional Chinese herb tea rich
      in sophoricoside that is an isoflavone glycoside. The aim of current study was to
      investigate the hepatic protective effect of sophoricoside in high fructose (HF)
      diet fed mice. Healthy male mice were fed 30% fructose water and treated 80 and
      160 mg/kg.bw sophoricoside continuously for 8 wk. Our data showed that
      administration of sophoricoside at 80 and 160 mg/kg.bw observably decreased the
      body weight and liver weight in HF-fed mice. It was found that the treatment of
      sophoricoside decreased the hepatic cholesterol and triglyceride levels, and
      serum low-density lipoprotein-cholesterol and apolipoprotein-B levels, and
      elevated the serum high-density lipoprotein-cholesterol and apolipoprotein-A1
      levels. Moreover, the administration of sophoricoside decreased the HF-caused
      elevations of hepatic malonaldehyde, interleukin-1 and tumor necrosis factor
      alpha levels, while increased the HF-induced decreases of hepatic superoxide
      dismutase and glutathione peroxidase activities. Meanwhile, serum aspartate
      aminotransferase, alanine aminotransferase, and alkaline phosphatase activities
      were reduced by treatment of sophoricoside in HF-fed mice. Histopathology of
      hematoxylin and eosin (H&E) and oil red O staining of liver tissues also
      confirmed the beneficial effects of sophoricoside against liver injury induced by
      HF-diet in mice. These findings indicated that sophoricoside may be a novel
      natural isoflavone for alleviating HF-induced liver injury. PRACTICAL
      APPLICATION: Fruit of Sophora japonica L. is a traditional herb tea and it
      recently becomes popular in China. Sophoricoside is an isoflavone glycoside
      (Genistein-4'-O-beta-d-glucopyranoside) isolated from S. japonical L, and it
      possessed differential effects on the body health. The ingestion of sophoricoside
      or sophora fruit tea may be a novel strategy to prevent non-alcoholic fatty liver
      disease.

PMID- 29350758
TI  - Obesity and Pediatric Drug Development.
AB  - There is a lack of dosing guidelines for use in obese children. Moreover, the
      impact of obesity on drug safety and clinical outcomes is poorly defined. The
      paucity of information needed for the safe and effective use of drugs in obese
      patients remains a problem, even after drug approval. To assess the current
      incorporation of obesity as a covariate in pediatric drug development, the
      pediatric medical and clinical pharmacology reviews under the Food and Drug
      Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act
      (FDASIA) of 2012 were reviewed for obesity studies. FDA labels were also reviewed
      for statements addressing obesity in pediatric patients. Forty-five drugs studied
      in pediatric patients under the FDA Amendments Act were found to have statements
      and key words in the medical and clinical pharmacology reviews and labels related
      to obesity. Forty-four products were identified similarly with pediatric studies
      under FDASIA. Of the 89 product labels identified, none provided dosing
      information related to obesity. The effect of body mass index on drug
      pharmacokinetics was mentioned in only 4 labels. We conclude that there is little
      information presently available to provide guidance related to dosing in obese
      pediatric patients. Moving forward, regulators, clinicians, and the
      pharmaceutical industry should consider situations in drug development in which
      the inclusion of obese patients in pediatric trials is necessary to facilitate
      the safe and effective use of new drug products in the obese pediatric
      population.

PMID- 29350761
TI  - Laser-Assisted Endoscopic Stapedectomy: A Prospective Study.
AB  - Objective To improve the techniques required to perform a stapedotomy without
      prosthesis (stapedioplasty). Study Design New infrared lasers were evaluated for
      potential use in otological surgery in guinea pigs. A prospective human trial of
      34 primary stapes operations using the Argon ion laser was performed, with 11
      stapedioplasties and 23 conventional stapedotomies as controls. Methods Laser
      tissue interactions were evaluated for temporal bone and live guinea pig tissues,
      measuring crater histology and labyrinthine temperature elevations. Patients
      undergoing stapedioplasty had Argon ion laser cuts with endoscopic assistance
      made in the anterior crus and footplate to mobilize the posterior segment of the
      stapes while the anterior portion remained fixed. Results Diode laser (808-nm)
      vaporization craters and temperature elevations in the vestibule were suitable
      for clinical use. Overall, stapedioplasty patients' hearing was improved with air
      bone gap closure to a mean of 8.3 dB (SD +/- 9.8 dB). Conclusions Patients with
      anterior footplate otosclerosis are candidates for stapedioplasty preserving the
      annular ring and stapes tendon and eliminating prosthesis complications. High
      resolution small endoscopes, coupled with Argon ion or diode lasers promise to
      improve stapes visualization, enhancing the ability to perform minimally invasive
      surgery on the stapes footplate.

PMID- 29350759
TI  - Extreme rainfall affects assembly of the root-associated fungal community.
AB  - Global warming is resulting in increased frequency of weather extremes. Root
      associated fungi play important roles in terrestrial biogeochemical cycling
      processes, but the way in which they are affected by extreme weather is unclear.
      Here, we performed long-term field monitoring of the root-associated fungus
      community of a short rotation coppice willow plantation, and compared community
      dynamics before and after a once in 100 yr rainfall event that occurred in the UK
      in 2012. Monitoring of the root-associated fungi was performed over a 3-yr period
      by metabarcoding the fungal internal transcribed spacer (ITS) region. Repeated
      soil testing and continuous climatic monitoring supplemented community data, and
      the relative effects of environmental and temporal variation were determined on
      the root-associated fungal community. Soil saturation and surface water were
      recorded throughout the early growing season of 2012, following extreme rainfall.
      This was associated with a crash in the richness and relative abundance of
      ectomycorrhizal fungi, with each declining by over 50%. Richness and relative
      abundance of saprophytes and pathogens increased. We conclude that extreme
      rainfall events may be important yet overlooked determinants of root-associated
      fungal community assembly. Given the integral role of ectomycorrhizal fungi in
      biogeochemical cycles, these events may have considerable impacts upon the
      functioning of terrestrial ecosystems.

PMID- 29350762
TI  - Occurrence of Ochratoxins, Fumonisin B2 , Aflatoxins (B1 and B2 ), and Other
      Secondary Fungal Metabolites in Dried Date Palm Fruits from Egypt: A Mini-Survey.
AB  - : This study was conducted to investigate the natural co-occurrence of 295 fungal
      and bacterial metabolites in 28 samples of dried date palm fruits collected from
      different shops distributed in Assiut Governorate, Upper Egypt in 2016.
      Extraction and quantification of the target analytes were done using the "dilute
      and shoot" approach followed by liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) analysis. In total, 30 toxic fungal metabolites were detected. Among
      these metabolites, 4 types of ochratoxins including ochratoxin type A and B were
      quantified in 3 samples (11%) with a contamination range from 1.48 to 6070 MUg/kg
      for ochratoxin A and from 0.28 to 692 MUg/kg for ochratoxin B. In addition,
      fumonisin B2 was observed in 2 (7%) samples with contamination levels ranging
      from 4.99 to 16.2 MUg/kg. The simultaneous detection of fumonisin B2 in the same
      contaminated samples with ochratoxins indicates the fungal attack by Aspergillus
      niger species during storage. Only 1 sample was contaminated with aflatoxin B1
      (14.4 MUg/kg) and B2 (2.44 MUg/kg). The highest maximum concentration (90400
      MUg/kg) was for kojic acid that contaminated 43% of the samples. To the best of
      the authors' knowledge, this is the first report of the natural co-occurrence of
      fumonisin B2 and ochratoxin A and B in addition to a wide range of other fungal
      metabolites in date palm fruits. PRACTICAL APPLICATION: Mycotoxins are secondary
      metabolites produced by different fungi. These metabolites pose a potential risk
      on human health since they contaminate many food commodities. Among these, date
      palm fruits which are an integral part of diet in several countries. Therefore,
      detection of mycotoxins is a prerequisite to insure the safety of food. Here,
      different types of mycotoxins have been detected in levels that may have health
      hazard.

PMID- 29350764
TI  - The Protective Effect of Antarctic Krill Oil on Cognitive Function by Inhibiting
      Oxidative Stress in the Brain of Senescence-Accelerated Prone Mouse Strain 8
      (SAMP8) Mice.
AB  - : Alzheimer's disease (AD) is a common neurodegenerative disorder, and oxidative
      stress plays a vital role in its progression. Antarctic krill oil (AKO) is rich
      in polyunsaturated fatty acids, which has various biological activities, such as
      improving insulin sensitivity, alleviating inflammation and ameliorating
      oxidative stress. In this study, the protective effect of AKO against AD were
      investigated in senescence-accelerated prone mouse strain 8 (SAMP8) mice. Results
      showed that treatment with AKO could effectively ameliorate learning and memory
      deficits and ease the anxiety in SAMP8 mice by Morris water maze, Barnes maze
      test and open-field test. Further analysis indicated that AKO might reduce beta
      amyloid (Abeta) accumulation in hippocampus through decreasing the contents of
      malondialdehyde (MDA) and 7,8-dihydro-8-oxoguanine (8-oxo-G), increasing the
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the
      brain of SAMP8 mice. PRACTICAL APPLICATION: The results of Morris water maze,
      Barnes maze test and open-field test indicated that Antarctic krill oil (AKO)
      improved the cognitive function and anxiety of SAMP8 mice. AKO reduced the
      Abeta42 level in hippocampus of SAMP8 mice. AKO ameliorated oxidative stress in
      brain rather than in serum and liver of SAMP8 mice.

PMID- 29350765
TI  - Probability and correlates of nicotine dependence among smokers with and without
      major depressive disorder: Results from the national epidemiology survey on
      alcohol and related conditions.
AB  - PURPOSE: This study aims to use data from a nationally representative survey to
      examine the correlates of nicotine dependence among smokers with and without
      major depressive disorder. METHODS: Data were drawn from the Wave 1 of the
      National Epidemiology Survey on Alcohol and Related Conditions (NESARC, 2001
      2002). Logistic regression analyses taking into account the complex sampling
      design were used to examine the correlates of nicotine dependence. RESULTS: The
      typical correlates of nicotine dependence (odds > 1.44 or 1/1.44, effect size (d)
      > .2) were age, race, employment, weight, and the interaction effects of gender
      with age of first use, age at onset of daily smoking, and quantity of smoking.
      CONCLUSION AND PRACTICE IMPLICATIONS: This study will increase psychiatric
      nurses' understanding and awareness regarding the correlates of nicotine
      dependence.

PMID- 29350763
TI  - Molecular allergen profiling in horses by microarray reveals Fag e 2 from
      buckwheat as a frequent sensitizer.
AB  - BACKGROUND: Companion animals are also affected by IgE-mediated allergies, but
      the eliciting molecules are largely unknown. We aimed at refining an allergen
      microarray to explore sensitization in horses and compare it to the human IgE
      reactivity profiles. METHODS: Custom-designed allergen microarray was produced on
      the basis of the ImmunoCAP ISAC technology containing 131 allergens. Sera from 51
      horses derived from Europe or Japan were tested for specific IgE reactivity. The
      included horse patients were diagnosed for eczema due to insect bite
      hypersensitivity, chronic coughing, recurrent airway obstruction and urticaria or
      were clinically asymptomatic. RESULTS: Horses showed individual IgE-binding
      patterns irrespective of their health status, indicating sensitization. In
      contrast to European and Japanese human sensitization patterns, frequently
      recognized allergens were Aln g 1 from alder and Cyn d 1 from Bermuda grass,
      likely due to specific respiratory exposure around paddocks and near the ground.
      The most prevalent allergen for 72.5% of the tested horses (37/51) was the 2S
      albumin Fag e 2 from buckwheat, which recently gained importance not only in
      human but also in horse diet. CONCLUSION: In line with the One Health concept,
      covering human health, animal health and environmental health, allergen
      microarrays provide novel information on the allergen sensitization patterns of
      the companion animals around us, which may form a basis for allergen-specific
      preventive and therapeutic concepts.

PMID- 29350766
TI  - Untangling the complexity of limb-girdle muscular dystrophies.
AB  - The limb-girdle muscular dystrophies (LGMDs) are a group of genetically
      heterogeneous, autosomal inherited muscular dystrophies with a childhood to adult
      onset, manifesting with hip- and shoulder-girdle muscle weakness. When the term
      LGMD was first conceptualized in 1954, it was thought to be a single entity.
      Currently, there are 8 autosomal dominant (LGMD1A-1H) and 26 autosomal recessive
      (LGMD2A-2Z) variants according to the Online Mendelian Inheritance in Man
      database. In addition, there are other genetically identified muscular
      dystrophies with an LGMD phenotype not yet classified as LGMD. This highlights
      the entanglement of LGMDs, which represents an area in continuous expansion.
      Herein we aim to simplify the complexity of LGMDs by subgrouping them on the
      basis of the underlying defective protein and impaired function. Muscle Nerve 58:
      167-177, 2018.

PMID- 29350767
TI  - Revealing potential functions of VBNC bacteria in polycyclic aromatic
      hydrocarbons biodegradation.
AB  - : The bioremediation of polycyclic aromatic hydrocarbon (PAH)-contaminated sites
      is not running smoothly, because of the lower activity of PAH-degrading bacteria
      in actual bioremediation applications. The phenomenon of "viable but
      nonculturable" (VBNC) state may be a main limiting factor for their poor
      biodegradation capabilities of PAHs. Due to their abilities of entering into the
      VBNC state, most of bacterial populations with PAH-degradation potential remain
      unculturable. Resuscitation of VBNC bacteria will enhance the degradation
      capability of indigenous bacteria which will eventually obtain their better
      capabilities in environmental bioremediation. Although evidences have been
      presented indicating that resuscitation of VBNC bacteria in polychlorinated
      biphenyl (PCB)-contaminated environments not only significantly enhanced PCB
      degradation, but also obtained novel highly efficient PCB-degrading bacteria,
      scanty information is available on the VBNC bacteria in PAH-contaminated sites.
      VBNC bacteria, as a vast majority of potential microbial resource could be the
      repository of novel highly efficient PAH-biodegraders. Therefore, studies need to
      be done on resuscitation of VBNC bacteria to overcome key bottlenecks in
      bioremediation of PAH-contaminated sites. This mini-review provides a new insight
      into the potential functions of VBNC bacteria in PAHs biodegradation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: As the vast majority microbial resource,
      viable but nonculturable (VBNC) bacteria, which showed their potential functions
      in polycyclic aromatic hydrocarbons (PAHs) biodegradation, can be of great
      significance in environmental bioremediation. It is therefore important to
      resuscitate VBNC bacteria for their better capabilities. Meanwhile, preventing
      the indigenous functional community from entering into the VBNC state will also
      maintain the high activity of PAH-degrading bacteria in actual bioremediation
      applications. Undoubtedly, much more work needs to be done to reveal indigenous
      micro-organisms in the VBNC state from the perspective of environmental
      functions.

PMID- 29350768
TI  - Diet affects gut microbiota and modulates hospitalization risk differentially in
      an international cirrhosis cohort.
AB  - : The relative ranking of cirrhosis-related deaths differs between high-/middle
      income countries. Gut microbiome is affected in cirrhosis and is related to diet.
      Our aim was to determine the effect of differing dietary habits on gut microbiota
      and clinical outcomes. Outpatient compensated/decompensated patients with
      cirrhosis and controls from Turkey and the United States underwent dietary and
      stool microbiota analysis. Patients with cirrhosis were followed till 90-day
      hospitalizations. Shannon diversity and multivariable determinants (Cox and
      binary logistic) of microbial diversity and hospitalizations were studied
      within/between groups. Two hundred ninety-six subjects (157 U.S.: 48 controls, 59
      compensated, 50 decompensated; 139 Turkey: 46 controls, 50 compensated, 43
      decompensated) were included. Patients with cirrhosis between cohorts had similar
      Model for End-Stage Liver Disease (MELD) scores. American patients with cirrhosis
      had more men, greater rifaximin/lactulose use, and higher hepatitis C/alcohol
      etiologies. Coffee intake was higher in Americans whereas tea, fermented milk,
      and chocolate intake were higher in Turkey. The entire Turkish cohort had a
      significantly higher microbial diversity than Americans, which did not change
      between their controls and patients with cirrhosis. In contrast, microbial
      diversity changed in the U.S.-based cohort and was the lowest in decompensated
      patients. Coffee, tea, vegetable, chocolate, and fermented milk intake predicted
      a higher diversity whereas MELD score, lactulose use, and carbonated beverage use
      predicted a lower microbial diversity. The Turkish cohort had a lower risk of 90
      day hospitalizations. On Cox and binary logistic regression, microbial diversity
      was protective against 90-day hospitalizations, along with coffee/tea, vegetable,
      and cereal intake. CONCLUSION: In this study of patients with cirrhosis and
      healthy controls from the United States and Turkey, a diet rich in fermented
      milk, vegetables, cereals, coffee, and tea is associated with a higher microbial
      diversity. Microbial diversity was associated with an independently lower risk of
      90-day hospitalizations. (Hepatology 2018;68:234-247).

PMID- 29350769
TI  - Myotilinopathy unmasked by statin treatment: A case report.

PMID- 29350770
TI  - The effects of work factors on nurses' job satisfaction, quality of care and
      turnover intentions in oncology.
AB  - AIMS: We examined the effects of perceived supervisor support, value congruence
      and hospital nurse staffing on nurses' job satisfaction through the satisfaction
      of the three psychological needs for autonomy, competence and relatedness. Then,
      we examined the links between job satisfaction and quality of care as well as
      turnover intentions from the workplace. BACKGROUND: There is growing interest in
      the relationships between work factors and nurses' job satisfaction. However,
      minimal research has investigated the effects of perceived supervisor support,
      value congruence and staffing on nurses' job satisfaction and the psychological
      mechanisms by which these factors lead to positive outcomes. DESIGN: A cross
      sectional questionnaire was distributed in 11 oncology units between September
      2015 - February 2016. METHOD: Data were collected from a sample of 144 French
      nurses who completed measures of perceived supervisor support, value congruence,
      staffing adequacy, psychological need satisfaction, job satisfaction, quality of
      care and turnover intentions. RESULTS: The hypothesized model was tested with
      path analyses. Results revealed that psychological need satisfaction partially
      mediated the effects of perceived supervisor support, value congruence and
      hospital nurse staffing on job satisfaction. Moreover, job satisfaction was
      positively associated with quality of care and negatively linked to turnover
      intentions. CONCLUSION: Overall, these findings provide insight into the
      influence of perceived supervisor support, value congruence and staffing on
      nurses' attitudes and behaviours.

PMID- 29350771
TI  - Recombinant relaxin protects liver transplants from ischemia damage by hepatocyte
      glucocorticoid receptor: From bench-to-bedside.
AB  - : Hepatic ischemia-reperfusion injury (IRI) represents a major risk factor of
      early graft dysfunction and acute/chronic rejection as well as a key obstacle to
      expanding the donor pool in orthotopic liver transplantation (OLT). Although
      glucocorticoid receptor (GR) signaling may enhance cytoprotective programs,
      clinical use of glucocorticoid is limited because of adverse effects, whereas
      clinical relevance of GR-facilitated cytoprotection in OLT remains unknown. We
      aimed to evaluate the significance of hepatic GR in clinical OLT and verify the
      impact of recombinant human relaxin (rhRLX), which may function as a GR agonist
      in a tissue/disease-specific manner. Fifty-one OLT patients were recruited under
      an institutional research board (IRB) protocol. Liver biopsies were collected
      after cold storage (presurgery) and 2 hours postreperfusion (before abdominal
      closure), followed by western blotting-assisted hepatic analyses. Forty-three
      percent of OLTs failed to increase GR perioperatively under surgical stress. Post
      /pre-GR ratios at postoperative day 1 correlated negatively with serum aspartate
      aminotransferase (AST)/cleaved caspase-3 and positively with B-cell lymphoma
      extra large (Bcl-xL)/B-cell lymphoma 2 (Bcl-2) levels. In a murine OLT model with
      extended (18-hour) cold storage, treatment with rhRLX ameliorated ischemia
      reperfusion (IR) damage and improved survival while up-regulating hepatocyte GR
      and Bcl-xL/Bcl-2 expression in OLT. rhRLX-induced GR suppressed hepatocyte high
      mobility group box 1 (HMGB1) translocation/release, accompanied by decreased Toll
      like receptor 4 (TLR4)/receptor for advanced glycation end products (RAGE),
      suppressed interleukin 1 beta (IL1beta), chemokine (C-C motif) ligand 2 (CCL2), C
      X-C motif chemokine (CXCL)10, tumor necrosis factor alpha (TNFalpha), CXCL1, and
      CXCL2 levels, and attenuated neutrophil/macrophage accumulation in OLT.
      Inhibition of GR in hepatocyte culture and in OLT diminished rhRLX-mediated
      cytoprotection. CONCLUSION: This translational study underscores the role of
      rhRLX-GR signaling as a regulator of hepatocellular protection against IR stress
      in OLT. In the context of a recent phase III clinical trial demonstrating
      positive outcomes of rhRLX in patients with acute heart failure, studies on rhRLX
      for the management of IRI in OLT recipients are warranted. (Hepatology
      2018;68:258-273).

PMID- 29350772
TI  - Arsenite-induced histone H3 modification and its effects on EGR1 and FOS
      expression in HeLa cells.
AB  - It is evident that trivalent arsenicals do not have mutagenicity, but they are
      human carcinogens. Recently, epigenetic modification has been considered as one
      of the important causes of arsenical carcinogenicity. Here we examined global
      histone H3 modification by trivalent inorganic arsenite (iAs(III)) and its
      contribution to gene expression in HeLa cells. iAs(III) induced histone H3K9
      dimethylation (H3K9me2) and trimethylation (H3K9me3), histone H3S10
      phosphorylation (H3S10p), histone H3T11 phosphorylation (H3T11p) and histone
      H3K9S10 trimethyl-phosphorylation (H3K9me3S10p). Among these modifications,
      H3S10p, H3T11p and H3K9me3S10p were observed as a punctate signal in interphase
      cells, which seems to associate with remodeling of the chromatin structure at the
      specific locus. A chromatin immunoprecipitation assay was performed to examine
      histone H3 modifications around the FOS, EGR1 and IL8 promoters, as previous
      studies revealed some relation between histone H3 modification and induction of
      these genes. iAs(III) increased H3S10p and H3K9me3S10p in the FOS promoter around
      the SRE/ELK1 binding site (-400 to -200) and CRE-binding site (-50). In contrast,
      histone H3 around the EGR1 promoter of SRE/CRE-binding site (-200 to -50) was
      modified to H3S10p and H3K9me3S10p by iAs(III). Reporter gene assays with
      deletion mutants of the FOS and EGR1 promoters revealed that the around SRE/ELK1
      site is important for iAs(III)-mediated FOS induction, and SRE/CRE site for EGR1
      induction. Collectively, these results demonstrate that iAs(III) induces histone
      H3 modifications around the transcription factor binding sites of the FOS and
      EGR1 promoter, and these modifications seem to be important in transcriptional
      activation of these genes.

PMID- 29350773
TI  - Effect of titanium dioxide nanoparticles on glucose homeostasis after oral
      administration.
AB  - As food additives, titanium dioxide nanoparticles (TiO2 NPs) have been widely
      used in various products that are usually simultaneously consumed with a high
      content of sugar, thus necessitating research on the effect of TiO2 NPs on
      glucose homeostasis. We conducted an animal study to explore the effect of orally
      administrated TiO2 NPs on glucose absorption and metabolism in rats at 0, 2, 10
      and 50 mg kg-1 body weight day-1 for 30 and 90 days. The results showed that oral
      exposure to TiO2 NPs caused a slight and temporary hypoglycemic effect in rats at
      30 days post-exposure but recovered at 90 days post-exposure. Decreased levels of
      intestinal glucose absorption and increased levels of hepatic glucose metabolism
      may be responsible for the hypoglycemic effect. Remodeling of the villi in the
      small intestine that decreased the surface area available for glucose absorption
      and increased levels of hepatic glucose uptake, utilization and storage related
      to hepatocellular injury are supposed to be the mechanisms. Our results
      demonstrated that dietary intake of TiO2 NPs as food additives could affect the
      absorption and metabolism of glucose.

PMID- 29350774
TI  - Hepatitis B virus surface gene pre-S2 mutant as a high-risk serum marker for
      hepatoma recurrence after curative hepatic resection.
AB  - : Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular
      carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) is highly
      associated with HCC. This study analyzed the expression of the large form of
      surface protein in tumors and evaluated the LHBS with mutations within the pre-S2
      region as a high-risk recurrence marker in HCC patients after curative hepatic
      resection. By analyses using immunohistochemical staining (n = 12) and western
      blotting (n = 22), the HBV surface protein, which is mainly comprised of the
      major form of HBV surface antigen, was greatly diminished in the tumors. However,
      LHBS was not significantly decreased in tumorous regions, suggesting that LHBS
      maintains its expression in cancer development. A cohort of 175 patients with HBV
      related HCC who underwent curative hepatic resection was analyzed for pre-S gene
      mutations using Pre-S Gene Chip. Results of the multivariate regression analysis
      showed that the serum pre-S2 mutant level and the American Joint Committee on
      Cancer stage were the two main independent high-risk factors for recurrence. A
      Cox proportional hazards analysis also revealed a prediction model, which
      indicated the recurrence-free survival rate along with the time after surgery;
      this was developed and further validated in an independent HCC cohort. Receiver
      operating characteristic curve analysis revealed that the model showed close
      sensitivities in the main and validation cohorts (area under the curve values,
      0.741 and 0.704, respectively). CONCLUSION: Unlike the major HBV surface antigen,
      LHBS is mostly expressed in the tumorous regions of HBV-induced HCC, indicating
      that it plays a unique role in tumor progression; the relative level of pre-S2
      mutant in serum is, independently of tumor stage, an important high-risk marker
      for HCC recurrence after primary hepatic resection. (Hepatology 2018).

PMID- 29350775
TI  - Randomized trial of transcranial direct current stimulation for poststroke
      dysphagia.
AB  - OBJECTIVE: We evaluated whether transcranial direct current stimulation (tDCS) is
      able to enhance dysphagia rehabilitation following stroke. Besides relating
      clinical effects with neuroplastic changes in cortical swallowing processing, we
      aimed to identify factors influencing treatment success. METHODS: In this double
      blind, randomized study, 60 acute dysphagic stroke patients received
      contralesional anodal (1mA, 20 minutes) or sham tDCS on 4 consecutive days.
      Swallowing function was thoroughly assessed before and after the intervention
      using the validated Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) and
      clinical assessment. In 10 patients, swallowing-related brain activation was
      recorded applying magnetoencephalography before and after the intervention. Voxel
      based statistical lesion pattern analysis was also performed. RESULTS: Study
      groups did not differ according to demographic data, stroke characteristics, or
      baseline dysphagia severity. Patients treated with tDCS showed greater
      improvement in FEDSS than the sham group (1.3 vs 0.4 points, mean difference =
      0.9, 95% confidence interval [CI] = 0.4-1.4, p < 0.0005). Functional recovery was
      accompanied by a significant increase of activation (p < 0.05) in the
      contralesional swallowing network after real but not sham tDCS. Regarding
      predictors of treatment success, for every hour earlier that treatment was
      initiated, there was greater improvement on the FEDSS (adjusted odds ratio =
      0.99, 95% CI = 0.98-1.00, p < 0.05) in multivariate analysis. Stroke location in
      the right insula and operculum was indicative of worse response to tDCS (p <
      0.05). INTERPRETATION: Application of tDCS over the contralesional swallowing
      motor cortex supports swallowing network reorganization, thereby leading to
      faster rehabilitation of acute poststroke dysphagia. Early treatment initiation
      seems beneficial. tDCS may be less effective in right-hemispheric insulo
      opercular stroke. Ann Neurol 2018;83:328-340.

PMID- 29350776
TI  - The existential experience of everyday life with systemic lupus erythematosus.
AB  - AIM: To explore from the perspective of women the nature of basic existential
      conditions while living with systemic lupus erythematosus. BACKGROUND: Systemic
      lupus erythematosus has an unpredictable disease course and is documented to
      cause an existential rearrangement of life. The significance of changes in
      existential conditions and related experiences are unclear in the context of
      nursing and women with systemic lupus erythematosus. DESIGN: A qualitative design
      guided by Van Manen's hermeneutic-phenomenological methodology. METHOD:
      Individual in-depth interviews with 15 women diagnosed with systemic lupus
      erythematosus and of various ages, disease durations and severities were
      undertaken from September 2013 - October 2015. Data were analysed following van
      Manen's phenomenological approach and using drawing as an interpretive tool.
      FINDINGS: The main existential experience was interpreted as a person "moving
      with the waves of systemic lupus erythematosus" constituted by the themes
      "oscillating between presence and absence of systemic lupus erythematosus,"
      "recognizing space and bodily possibilities and limitations" and "being enriched
      through relationships and activities." When systemic lupus erythematosus was
      flaring, well-being was threatened and a laborious time to escape the feeling of
      a setback-in-life persisted long after the disease was medically under control.
      CONCLUSION: Daily life with systemic lupus erythematosus is conditioned by a
      prominent need to be in existential motion, related to the absence and presence
      of systemic lupus erythematosus. The experience of a setback-in-life by illness
      might challenge well-being and indicates that periods of disease flares or
      disturbing symptoms are critical time points to provide support.

PMID- 29350777
TI  - The pathology of lumbosacral lipomas: macroscopic and microscopic disparity have
      implications for embryogenesis and mode of clinical deterioration.
AB  - AIMS: Lumbosacral lipomas (LSL) are congenital disorders of the terminal spinal
      cord region that have the potential to cause significant spinal cord dysfunction
      in children. They are of unknown embryogenesis with variable clinical
      presentation and natural history. It is unclear whether the spinal cord
      dysfunction reflects a primary developmental dysplasia or whether it occurs
      secondarily to mechanical traction (spinal cord tethering) with growth. While
      different anatomical subtypes are recognised and classified according to
      radiological criteria, these subtypes correlate poorly with clinical prognosis.
      We have undertaken an analysis of surgical specimens in order to describe the
      spectrum of histological changes that occur and have correlated the histology
      with the anatomical type of LSL to determine if there are distinct histological
      subtypes. METHODS AND RESULTS: The histopathology was reviewed of 64 patients who
      had undergone surgical resection of LSL. The presence of additional tissues and
      cell types were recorded. LSLs were classified from pre-operative magnetic
      resonance imaging (MRI) scans according to Chapman classification. Ninety-five
      per cent of the specimens consisted predominantly of mature adipocytes with all
      containing thickened bands of connective tissue and peripheral nerve fibres, 91%
      of samples contained ectatic blood vessels with thickened walls, while 22%
      contained central nervous system (CNS) glial tissue. Additional tissue was
      identified of both mesodermal and neuroectodermal origin. CONCLUSIONS: Our
      analysis highlights the heterogeneity of tissue types within all samples, not
      reflected in the nomenclature. The diversity of tissue types, consistent across
      all subtypes, challenges currently held notions regarding the embryogenesis of
      LSLs and the assumption that clinical deterioration is due simply to tethering.

PMID- 29350778
TI  - Re: Folate status and autism spectrum disorders.

PMID- 29350779
TI  - Studying Infant Feeding and Growth: Timing is Everything.

PMID- 29350780
TI  - An evolutionary concept analysis of futility in health care.
AB  - AIM: To report a concept analysis of futility in health care. BACKGROUND: Each
      member of the healthcare team: the physician, the nurse, the patient, the family
      and all others involved perceive futility differently. The current evidence and
      knowledge in regard to futility in health care manifest a plethora of
      definitions, meanings and interpretations without consensus. DESIGN: Concept
      analysis. DATA SOURCES: Databases searched included Medline, Cumulative Index of
      Nursing and Allied Health Literature, Academic Search Premier, Cochrane Database
      of Systematic Reviews and PsycINFO. Search terms included "futil*," "concept
      analysis," "concept," "inefficacious," "non-beneficial," "ineffective" and
      "fruitless" from 1935-2016 to ensure a historical perspective of the concept. A
      total of 106 articles were retained to develop the concept. METHODS: Rogers'
      evolutionary concept analysis was used to evaluate the concept of futility from
      ancient medicine to the present. RESULTS: Seven antecedents (the patient/family
      autonomy, surrogate decision-making movement, the patient-family/physician
      relationship, physician authority, legislation and court rulings, catastrophic
      events and advancing medical technology) lead to four major attributes
      (quantitative, physiologic, qualitative, and disease-specific). Ultimately,
      futile care could lead to consequences such as litigation, advancing technology,
      increasing healthcare costs, rationing, moral distress and ethical dilemmas.
      CONCLUSION: Futility in health care demonstrates components of a cyclical process
      and a consensus definition is proposed. A framework is developed to clarify the
      concept and articulate relationships among attributes, antecedents and
      consequences. Further testing of the proposed definition and framework are
      needed.

PMID- 29350781
TI  - Effects of work environment and job characteristics on the turnover intention of
      experienced nurses: The mediating role of work engagement.
AB  - AIM: To assess turnover intention among experienced nurses and explore the
      effects of work environment, job characteristics and work engagement on turnover
      intention. BACKGROUND: The nursing shortage is an urgent concern in China. A high
      turnover rate of experienced nurses could have serious effects on the quality of
      care, costs and the efficiency of hospitals. It is crucial to explore the
      predictors of turnover intention and develop strategies tailored to experienced
      nurses. DESIGN: A descriptive, cross-sectional survey design. METHODS: A total of
      778 experienced nurses from seven hospitals was surveyed on their work
      engagement, job characteristics, work environment and turnover intention in March
      May 2017. Structural equation modelling was used to test a theoretical model and
      the hypotheses. RESULTS: The results showed that 35.9% of experienced nurses had
      high-level turnover intention. The final model explained 50% of the variance in
      experienced nurses' turnover intention and demonstrated that: (1) work
      environment was positively associated with higher work engagement and lower
      turnover intention and work engagement partially mediated the relationship
      between work environment and turnover intention; and (2) job characteristics were
      positively related to higher work engagement and lower turnover intention and
      work engagement fully mediated the relationship between job characteristics and
      turnover intention. CONCLUSIONS: The study confirms the intrinsic and extrinsic
      motivators on work engagement posited by job demands-resources model. Theory
      driven strategies to improve work environment, enhance job characteristics and
      promote wok engagement are needed to address the nursing shortage and high
      turnover intention among experienced nurses.

PMID- 29350782
TI  - Realism and Pragmatism in a mixed methods study.
AB  - AIM: A discussion of how adopting a Realist rather than Pragmatist methodology
      affects the conduct of mixed methods research. BACKGROUND: Mixed methods
      approaches are now extensively employed in nursing and other healthcare research.
      At the same time, realist methodology is increasingly used as philosophical
      underpinning of research in these areas. However, the standard philosophical
      underpinning of mixed methods research is Pragmatism, which is generally
      considered incompatible or at least at odds with Realism. This paper argues that
      Realism can be used as the basis of mixed methods research and that doing so
      carries advantages over using Pragmatism. A mixed method study into patient
      handover reports is used to illustrate how Realism affected its design and how it
      would have differed had a Pragmatist approach been taken. DESIGN: Discussion
      Paper. DATA SOURCES: Philosophers Index; Google Scholar. IMPLICATIONS FOR
      NURSING: Those undertaking mixed methods research should consider the use of
      Realist methodology with the addition of some insights from Pragmatism to do with
      the start and end points of enquiry. CONCLUSION: Realism is a plausible
      alternative methodology for those undertaking mixed methods studies.

PMID- 29350783
TI  - Malignant mesothelioma in situ.
AB  - AIMS: The existence of malignant mesothelioma in situ (MIS) is often postulated,
      but there are no accepted morphological criteria for making such a diagnosis.
      METHODS AND RESULTS: Here we report two cases that appear to be true MIS on the
      basis of in-situ genomic analysis. In one case the patient had repeated
      unexplained pleural unilateral effusions. Two thoracoscopies 9 months apart
      revealed only visually normal pleura. Biopsies from both thoracoscopies showed
      only a single layer of mildly reactive mesothelial cells. However, these cells
      had lost BRCA1-associated protein 1 (BAP1) and showed loss of cyclin-dependent
      kinase inhibitor 2 (CDKN2A) (p16) by fluorescence in-situ hybridisation (FISH).
      NF2 was not deleted by FISH but 28% of the mesothelial cells showed hyperploidy.
      Six months after the second biopsy the patient has persisting effusions but no
      evidence of pleural malignancy on imaging. The second patient presented with
      ascites and minimal omental thickening on imaging, but no visual evidence of
      tumour at laparoscopy. Omental biopsy showed a single layer of minimally atypical
      mesothelial cells with rare tiny foci of superficial invasion of fat. BAP1
      immunostain showed loss of nuclear BAP1 in all the surface mesothelial cells and
      the invasive cells. There was CDKN2A deletion, but no deletion of NF2 by FISH.
      CONCLUSIONS: These cases show that morphologically bland single-layered surface
      mesothelial proliferations with molecular alterations seen previously only in
      invasive malignant mesotheliomas exist, and presumably represent malignant MIS.
      More cases are need to understand the frequency of such changes and the time
      course over which invasive tumour develops.

PMID- 29350784
TI  - Novel cardiovascular magnetic resonance oxygenation approaches in understanding
      pathophysiology of cardiac diseases.
AB  - Cardiovascular magnetic resonance imaging (CMR) permits accurate phenotyping of
      many cardiac diseases. CMR's inherent advantages are its non-invasive nature,
      lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it
      is able to assess many aspects of cardiac anatomy, structure and function.
      Specifically, it can characterize myocardial tissue, myocardial function,
      myocardial mass, myocardial blood flow/perfusion, irreversible and reversible
      injury, all with a high degree of accuracy and reproducibility. Hence, CMR is a
      powerful tool in clinical and pre-clinical research. In recent years there have
      been novel advances in CMR myocardial tissue characterization. Oxygenation
      sensitive CMR (OS-CMR) is a novel non-invasive, contrast independent technique
      that permits direct quantification of myocardial tissue oxygenation, both at rest
      and during stress. In this review, we will address the principles of the OS-CMR
      technique, its recent advances and summarize the studies in the effects of
      oxygenation on cardiac diseases.

PMID- 29350785
TI  - The monocyte Fcgamma receptors FcgammaRI/gamma and FcgammaRIIA differ in their
      interaction with Syk and with Src-related tyrosine kinases.
AB  - There are important differences in signaling between the Fc receptor for
      immunoglobulin G (IgG) FcgammaRIIA, which uses the Ig tyrosine-activating motif
      (ITAM) within its own cytoplasmic domain, and FcgammaRI, which transmits signals
      by means of an ITAM located within the cytoplasmic domain of its associated gamma
      chain. For example, in transfected epithelial cells and COS-1 cells, FcgammaRIIA
      mediates phagocytosis of IgG-coated red blood cells more efficiently than does
      FcgammaRI/gamma, and enhancement of phagocytosis by Syk kinase is more pronounced
      for FcgammaRI/gamma than for FcgammaRIIA. In addition, structure/function studies
      indicate that the gamma-chain ITAM and the FcgammaRIIA ITAM have different
      requirements for mediating the phagocytic signal. To study the differences
      between FcgammaRIIA and FcgammaRI/gamma, we examined the interaction of
      FcgammaRIIA and the FcgammaRI/gamma chimera FcgammaRI-gamma-gamma (extracellular
      domain-transmembrane domain-cytoplasmic domain) with Syk kinase and with the Src
      related tyrosine kinases (SRTKs) Hck and Lyn in transfected COS-1 cells. Our data
      indicate that FcgammaRIIA interacts more readily with Syk than does FcgammaRI
      gamma-gamma and suggest that one consequence may be the greater phagocytic
      efficiency of FcgammaRIIA compared with FcgammaRI/gamma. Furthermore, individual
      SRTKs affect the efficiency of phagocytosis differently for FcgammaRI-gamma-gamma
      and FcgammaRIIA and also influence the ability of these receptors to interact
      with Syk kinase. Taken together, the data suggest that differences in signaling
      by FcgammaRIIA and FcgammaRI-gamma-gamma are related in part to interaction with
      Syk and Src kinases and that individual SRTKs play different roles in FcgammaR
      mediated phagocytosis.

PMID- 29350786
TI  - Multiple biological defects caused by calycosin-7-O-beta-d-glucoside in the
      nematode Caenorhabditis elegans are associated with the activation of oxidative
      damage.
AB  - Calycosin-7-O-beta-d-glucoside (CG) is an important active isoflavone compound in
      Radix Astragali that has many bioactivities. However, the toxicological effects
      and related toxicological mechanism of CG have been rarely documented. The
      purpose of the present study was to evaluate the toxicity effects of CG on the
      model organism Caenorhabditis elegans. Some characteristics of the nematode,
      including lifespan, movement behavior and reproductive capacity, were used to
      detect the toxic effects of CG on C. elegans. The results showed that CG could
      shorten the lifespan of C. elegans by up to 25.3% and severely damage the
      movement of N2 larvae compared with the control group. Moreover, CG could prolong
      the generation times and reduce the brood sizes. Furthermore, CG promoted the
      formation of reactive oxygen species (ROS), which caused oxidative stress,
      increased the mRNA expression of sod-1, sod-2, sod-3, sod-5, ctl-1, ctl-2 and ctl
      3, and induced the antioxidant enzymes activities of superoxide dismutase and
      catalase to scavenge free radicals. However, antioxidant treatment experiments
      showed that Trolox could reduce the level of ROS caused by CG to the normal state
      of the control. These results suggested that the generation and elimination of
      ROS could not restore normal homeostasis in C. elegans treated by CG. These
      findings indicated that the activation of oxidative damage is one of the most
      important toxic mechanisms of CG in C. elegans.

PMID- 29350787
TI  - Fathers' experiences with their preterm babies admitted to neonatal intensive
      care unit: A multi-method study.
AB  - AIM: The aim of this study was to investigate fathers' emotional experiences of
      their infant's preterm birth and subsequent stay in neonatal intensive care unit.
      BACKGROUND: When a baby is born preterm, there is also the premature interruption
      of the process of preparation for fatherhood. As a result, the impact on fathers
      of the preterm birth can bring negative consequences for the development of
      father-infant relationship. DESIGN: A multi-method approach was used which
      included ethnographic observation, semi-structured interviews with fathers, a
      self-report questionnaire and clinical information between September 2015-March
      2017. METHOD: Data were analysed using a mixed-method: a thematic analysis of
      data from the interviews and quantitative analyses to detect possible clusters of
      fathers' emotional experiences and associations between clusters and fathers'
      and/or infants' characteristics. RESULTS: Two clusters were identified. The
      "fathers-of-preterm-infants" touched their baby as soon as they were given the
      opportunity and without fear that they would harm their infant. They were struck
      by their baby's physical appearance. In contrast, the "preterm fathers" preferred
      not to touch their baby when first given the chance, for fear of
      breaking/damaging/infecting her/him. They were struck both by the baby's physical
      appearance and by the technology/equipment around her/him and were afraid that
      their infant would die. All the "fathers-of-preterm-infants", but only just over
      half of the "preterm fathers", were actively engaged in their infant's care.
      Clusters were associated with the infant's gestational age. CONCLUSION: Fathers
      of preterm infants should receive personalized support specifically addressed to
      them and based on the infant's gestational age.

PMID- 29350788
TI  - Reliability and validity of the Atopic Dermatitis Symptom Score (ADSS).
AB  - BACKGROUND: We have developed the Atopic Dermatitis Symptom Score (ADSS) by which
      patients or parents can easily assess and record AD symptoms on a daily basis in
      a smartphone application. The aim of this study was to evaluate the reliability
      and validity of the ADSS. METHODS: We enrolled 307 children and adolescents with
      AD. Parents or caregivers were asked to record daily symptoms of the patients
      (itching, sleep disturbance, erythema, dryness, oozing, and edema) using a scale
      of 0-4. Statistical analyses consisted of the test-retest reliability, concurrent
      validity, minimal clinically important difference (MCID), responsiveness, floor
      or ceiling effects, and screening accuracy. Receiver-operating characteristic
      analyses were conducted to evaluate the ADSS cutoff point for predicting severe
      AD (SCORing AD [SCORAD] >=40). RESULTS: Test-retest reliability between daytime
      and night-time ADSS was good (intraclass correlation coefficient, 0.82 [95% CI:
      0.70-0.90]). An increase in ADSS was significantly associated with an increase in
      SCORAD (r = 0.64, P < .0001) (concurrent validity). The MCID was 4.1 points for
      the ADSS. There was a significant association between changes in ADSS and SCORAD
      (r = 0.56, P < .0001), indicating good responsiveness. At the optimal ADSS cutoff
      value of 7.0, sensitivity, specificity, and positive and negative predictive
      values were 88.4%, 78.6%, 21.1%, and 99.1%, respectively (screening accuracy).
      CONCLUSIONS: The ADSS can be a useful tool for self-assessment of skin symptoms
      in children with AD.

PMID- 29350789
TI  - TCR modifications that enhance chain pairing in gene-modified T cells can augment
      cross-reactivity and alleviate CD8 dependence.
AB  - T cell receptor (TCR) gene-modified T cells are a promising immunotherapy but
      require refinement to improve clinical responses and limit off-target toxicities.
      A variety of TCR and gene-delivery vector modifications have been developed to
      enhance introduced TCR expression and limit introduced/endogenous TCR chain
      mispairing, improving target antigen recognition and minimizing mispairing
      induced cross-reactivity. Using our well-characterized HCV1406 TCR, we previously
      compared the impact of various chain pairing enhancing modifications on TCR
      expression and cognate antigen recognition. HCV1406 TCR is also natively cross
      reactive against naturally occurring altered peptide ligands (APLs), which was
      shown to be dependent on high TCR surface density. In this report, we observed in
      a Jurkat model that absent TCR chain pairing competition alleviated CD8-dependent
      APL recognition and induced novel cross-reactivity of HCV1406 TCR. We then
      compared chain pairing enhancing modifications' effects on TCR cross-reactivity
      in Jurkat and T cells, showing C-terminal leucine zippers and constant region
      murinization alleviated CD8 dependence and induced novel APL recognition. While
      modifications enhancing TCR chain pairing intend to avoid cross-reactivity by
      limiting mispairing with the endogenous TCR, these data suggest they may also
      enhance natural cross-reactivity and reduce dependence on CD8. These observations
      have significant implications on the design/implementation of TCR gene-modified T
      cells.

PMID- 29350790
TI  - Outcomes and complications of Baerveldt glaucoma drainage implants for the
      treatment of uveitis-related glaucoma.

PMID- 29350792
TI  - FcgammaRIIIB stimulation promotes beta1 integrin activation in human neutrophils.
AB  - The molecular stimuli involved in receptor-induced integrin activation are still
      poorly defined. We have investigated the role of receptors for the Fc portion of
      immunoglobulin G molecules (FcgammaR) on activation of integrins in human
      neutrophils. Cross-linking of FcgammaRIIA induced an increase in surface
      expression of beta2 integrins but had no effect on beta1 integrins. In contrast,
      cross-linking of FcgammaRIIIB not only increased beta2 integrins on the cell
      surface but also induced beta1 integrin activation, as indicated by an increase
      in binding to fibronectin and the appearance of an activation epitope detected by
      the monoclonal antibody 15/7. The FcgammaRIIIB-induced increase of beta2
      integrins required Src-family tyrosine kinases, Syk kinase, and
      phosphatidylinositol-3 kinase (PI-3K), as the corresponding, specific inhibitors,
      PP2, Piceatannol, and LY294002, completely blocked it. Contrary to this,
      FcgammaRIIIB-indued beta1 integrin activation was not blocked by PP2 or LY294002.
      It was, however, enhanced by Piceatannol. After FcgammaRIIIB cross-linking,
      colocalization of FcgammaRIIIB and active beta1 integrins was detected on the
      neutrophil membrane. These data show, for the first time, that cross-linking of
      FcgammaRIIIB induces an inside-out signaling pathway that leads to beta1 integrin
      activation. This activation is independent of Src-family kinases, and PI-3K and
      may be induced in part by the interaction of FcgammaRIIIB with beta1 integrins.

PMID- 29350793
TI  - Thymocyte stimulation by anti-TCR-beta, but not by anti-TCR-alpha, leads to
      induction of developmental transcription program.
AB  - Anti-T cell receptor (aTCR) antibody (Ab) stimulation of T cells results in TCR
      down-modulation and T cell activation. Differences in the effect of anti-alpha
      chain and beta-chain Ab have been reported on thymocytes. Anti-beta-chain Ab but
      not anti-alpha-chain reagents cause long-term TCR down-modulation. However, both
      types of Ab result in TCR cross-linking and activate early steps in signal
      transduction. In this study, we show that TCR iternalization and calcium flux,
      hallmarks of T cell activation, are similar with aValpha and aVbeta treatment.
      Therefore, we have compared the gene expression profiles of preselection
      thymocytes stimulated with these reagents. We find that aValpha treatment does
      not cause any significant change in gene expression compared with control culture
      conditions. In contrast, aVbeta stimulation results in numerous changes in gene
      expression. The alterations of expression of genes known to be expressed in
      thymocytes are similar to changes caused by positive thymic selection, suggesting
      that the expression of some of the genes without known roles in thymocyte
      development and of novel genes whose expression is found to be altered may also
      be involved in this process.

PMID- 29350791
TI  - Comparison of outpatient medically attended and community-level influenza-like
      illness-New York City, 2013-2015.
AB  - BACKGROUND: Surveillance of influenza-like illness (ILI) in the United States is
      primarily conducted through medical settings despite a significant burden of non
      medically attended ILI. OBJECTIVES: To assess consistency between surveillance
      for respiratory viruses in outpatient and community settings using ILI
      surveillance from the Centers for Disease Control and Prevention Influenza
      Incidence Surveillance Project (IISP) and the Mobile Surveillance for Acute
      Respiratory Infections (ARI) and Influenza-Like Illness in the Community (MoSAIC)
      Study. METHODS: The Influenza Incidence Surveillance Project conducts ILI
      surveillance in 3 primary care clinics in New York City, and MoSAIC conducts
      community-based ILI/ARI surveillance through text messaging among a cohort of New
      York City residents. Both systems obtain respiratory specimens from participants
      with ILI/ARI and test for multiple pathogens. We conducted a retrospective review
      of ILI cases in IISP and MoSAIC from January 2013 to May 2015 with descriptive
      analyses of clinical and laboratory data. RESULTS: Five-hundred twelve MoSAIC and
      669 IISP participants met an ILI criteria (fever with cough or sore throat) and
      were included. Forty percent of MoSAIC participants sought care; the majority
      primary care. Pathogens were detected in 63% of MoSAIC and 70% of IISP cases. The
      relative distribution of influenza and other respiratory viruses detected was
      similar; however, there were statistically significant differences in the
      frequency that were not explained by care seeking. CONCLUSIONS: Outpatient and
      community-based surveillance in the one found similar timing and relative
      distribution of respiratory viruses, but community surveillance in a single
      neighborhood may not fully capture the variations in ILI etiology that occur more
      broadly.

PMID- 29350794
TI  - The role of electrodiagnosis with long exercise test in mcardle disease.
AB  - INTRODUCTION: In this study we evaluated the role of an electrodiagnostic
      provocative test (long exercise test) in McArdle disease. METHODS: Twenty-five
      McArdle patients and 2 control groups underwent an electrodiagnostic protocol
      with long exercise test (LET), consisting of recording the compound muscle action
      potential (CMAP) before and after 5 minutes of isometric contraction. RESULTS:
      The LET disclosed a postexercise decrease in CMAP amplitude in 23 of 25 McArdle
      patients. The immediate and long-lasting decrease differentiated McArdle patients
      from controls. Patients with a normal LET demonstrated milder symptoms and/or
      residual myophosphorylase activity. DISCUSSION: The LET is a sensitive, safe, and
      noninvasive provocative test that may guide clinicians toward molecular analysis
      of the myophosphorylase gene. The abnormalities observed on LET point toward
      complex biochemical mechanisms determined by the absence of myophosphorylase,
      beyond simple glycolytic blockade (ionic pump dysfunction, sarcolemmal
      inexcitability). The normal LET in patients with milder symptoms indicates a
      relationship of the LET with clinical severity, thus identifying it as a
      potential outcome measure. Muscle Nerve, 2018.

PMID- 29350795
TI  - Phacoemulsification and primary implantation with bag-in-the-lens intraocular
      lens in children with unilateral and bilateral cataract.
AB  - PURPOSE: To report outcome in a paediatric cohort with cataract extraction and
      implantation of bag-in-the-lens intraocular lens (BIL-IOL). METHODS: Children
      younger than 16 years of age subjected to phacoemulsification with primary
      implantation of BIL-IOL during 2009 through 2013 were analysed retrospectively.
      Exclusion criteria were uveitis or <=6 months of follow-up. RESULTS: In total,
      109 eyes of 84 children were included; 40 unilateral and 44 bilateral cataracts.
      For all eyes, median age at surgery was 2.5 years (range 2 weeks to 14.1 years)
      and 16 children (24 eyes) were <=6 weeks. Coexisting systemic disease was more
      common in children with bilateral cataract (24 patients, 54.5%) compared to
      unilateral cataract (6 patients, 15.0%, p < 0.0001). Ocular comorbidity was more
      common in unilateral cataracts; n = 14 eyes (35.0%) compared to bilateral
      cataracts; n = 10 eyes (14.5%; p = 0.017). Median follow-up was 2.8 years (range
      7 months to 5.8 years). During the follow-up period, 15 (13.8%) eyes developed
      glaucoma and five (4.6%) eyes required treatment for visual axis opacification
      (VAO). Corrected distance visual acuity (CDVA) for bilateral cataracts at last
      follow-up was 0.42 +/- 0.45 (logMAR; mean+/-SD) with 35 (55.6%) eyes attaining a
      CDVA of >=0.5 (dec). For unilateral cataracts mean CDVA was significantly poorer;
      0.67 +/- 0.51 (p = 0.010) with 15 (37.5%) eyes attaining a CDVA of >=0.5.
      CONCLUSION: For children having cataract surgery with primary implantation of BIL
      IOL, VAO is rare and visual outcome overall good. Unilateral cataracts are
      associated with a higher proportion of ocular comorbidity and poorer visual
      outcome.

PMID- 29350796
TI  - "Risk management" is a verb.
AB  - To optimally demonstrate the value of risk management, our actions must show the
      benefits. The American Society for Healthcare Risk Management (ASHRM) board needs
      to provide support through tools and resources. ASHRM members must show through
      their actions the value of risk management. And ASHRM members need to show the
      organization where actions and activities should be focused in the future.
      Actions show the value of enterprise risk management.

PMID- 29350798
TI  - Catastrophic events: Are you prepared?

PMID- 29350797
TI  - Case law update.

PMID- 29350799
TI  - Platelet binding to monocytes increases the adhesive properties of monocytes by
      up-regulating the expression and functionality of beta1 and beta2 integrins.
AB  - Human monocytes adhere to activated platelets, resulting in the formation of
      platelet-monocyte complexes (PMC). Complex formation depends on the interaction
      between platelet-displayed P-selectin and the specific ligand for P-selectin on
      leukocytes, P-selectin glycoprotein ligand-1 (PSGL-1). We have recently shown
      that monocytes within PMC have increased adhesive capacity to the activated
      endothelium. To better understand the effect of platelet binding on the capacity
      of monocytes to adhere to activated endothelium, the P-selectin-PSGL-1
      interaction-induced changes in integrin functionality were studied. The binding
      of platelets to monocytes via P-selectin-PSGL-1 interactions was shown to
      increase expression and activity of alpha4 beta1 and alphaM beta2 integrin, with
      a concomitant decrease in L-selectin expression. Furthermore, the binding of
      platelets to monocytes resulted in increased monocyte adhesion to intercellular
      adhesion molecule-1, vascular cell adhesion molecule-1, and fibronectin. Platelet
      binding was also responsible for an increase in monocyte transendothelial
      migration. Similar effects were observed after engagement of PSGL-1 with specific
      antibodies or with P-selectin immunoglobulin protein. Our data suggest that
      platelets, by binding via P-selectin to PSGL-1 on monocytes, induce up-regulation
      and activation of beta1 and beta2 integrins and increased adhesion of monocytes
      to activated endothelium. Hence, monocytes within PMC are in a higher state of
      activation and may have, therefore, an increased atherogenic capacity.

PMID- 29350800
TI  - Acquisition, remission, and persistence of eczema, asthma, and rhinitis in
      children.
AB  - BACKGROUND: Allergic sensitization is associated with eczema, asthma, and
      rhinitis. However, it is unknown whether and how allergic sensitization is
      associated over time with acquisition, remission, and persistence of these
      diseases and their comorbidity. OBJECTIVE: To gain a better understanding of
      factors including allergic sensitization transitions that influence the temporal
      pattern of asthma, eczema, and rhinitis and their comorbidity during childhood.
      METHODS: In the Isle of Wight birth cohort, information on allergic sensitization
      to common allergens was collected at ages 4, 10, and 18 years along with asthma,
      rhinitis, and eczema status determined by clinical diagnosis. Logistic
      regressions were used to estimate subsequent and concurrent odds ratios of
      diseases transition with allergic sensitization transition status as the main
      independent variable. Two transition periods were considered, 4 to 10 years of
      age and 10 to 18 years of age. RESULTS: The odds of new diagnosis of allergic
      disease (no-yes) was increased among subjects with acquired or persistent
      allergic sensitization to common allergens compared to subjects with no
      sensitization (acquisition of sensitization odds ratio [OR]=3.22, P < .0001;
      persistence of sensitization, OR=6.33, P < .0001). The odds of remission of
      allergic diseases (yes-no) was lower among subjects with acquired or sustained
      allergic sensitization (acquisition, OR=0.18, P = .0001; persistence, OR=0.085, P
      < .0001), compared to subjects not sensitized. Subjects with acquired or
      persistent allergic sensitization were also had higher odds for persistence of
      disease (yes-yes) than subjects not sensitized (acquisition, OR=5.49, P = .0001;
      persistence, OR=11.79, P < .0001). CONCLUSION: Transition of allergic
      sensitizations to common allergens is a prognostic factor for subsequent or
      concurrent transition of eczema, asthma, and rhinitis. Prevention or reduction in
      allergic sensitization has a potential to lead to remission of these conditions.

PMID- 29350801
TI  - Interview with Dr. Stephen J. McSorley and Ms. Aparna Srinivasan regarding
      Pivotal Advance: Secondary exposure to LPS suppresses CD4+ T cells and
      exacerbates murine typhoid.

PMID- 29350802
TI  - Cellular reprogramming: A new way to understand aging mechanisms.
AB  - Increased life expectancy, due to the rise in life quality and the decline in
      mortality rates, is leading to a society in which the population aged 60 and over
      is growing more rapidly than the entire population. Although various models and
      model organisms have been employed to investigate the mechanism of aging, induced
      pluripotent stem cells (iPSCs) are useful candidates to study human aging and age
      related human diseases. This work discusses how iPSCs can be used as an
      alternative to the model organisms such as yeast, Caenorhabditis elegans,
      Drosophila melanogaster, or the mouse. The main focus is the reprogramming
      technology of somatic cells which is thought to provide an important perspective
      for rejuvenation strategies. The effects and relationships between aging and cell
      reprogramming are discussed, and studies related to aging and cell reprogramming
      are critically reviewed. We believe that for future studies, different parameters
      and detailed quantitative experiments should be performed in order to clearly
      understand the effect of aging on human cell reprogramming with respect to
      programming efficiency and differentiation capacity. This way, new insights will
      be provided to prevent or even reverse the aging process. WIREs Dev Biol 2018,
      7:e308. doi: 10.1002/wdev.308 This article is categorized under: Adult Stem
      Cells, Tissue Renewal, and Regeneration > Stem Cells and Aging Adult Stem Cells,
      Tissue Renewal, and Regeneration > Regeneration Adult Stem Cells, Tissue Renewal,
      and Regeneration > Stem Cells and Disease.

PMID- 29350803
TI  - Thrombectomy outcomes for acute stroke patients with anterior circulation tandem
      lesions: a clinical registry and an update of a systematic review with meta
      analysis.
AB  - BACKGROUND AND PURPOSE: Although mechanical thrombectomy (MT) appears to be
      superior in stroke patients with extracranial carotid disease (ECD) compared to
      thrombolysis alone, the impact of emergent carotid stenting during MT remains
      unclear. The MT outcomes were assessed in anterior stroke patients with ECD,
      especially when combined with carotid stenting. METHODS: A retrospective analysis
      of our registry was performed and an update of a systematic review and meta
      analysis of MT studies with or without stenting for anterior circulation stroke
      with ECD published between November 2010 and April 2017 was conducted. RESULTS:
      In our registry, 46 patients with ECD underwent MT. In the meta-analysis
      including 13 primary studies plus our prospective registry data (590 patients in
      total), the successful reperfusion rate (modified thrombolysis in cerebral
      infarction score >=2b) reached 75% [95% confidence interval (CI) 69%-81%]. The
      rate of symptomatic intracranial haemorrhage (sICH) was 8% (95% CI 6%-11%), 90
      day favourable outcome was achieved in 50% (95% CI 42%-59%) and mortality rate
      was 16% (95% CI 11%-22%). When using carotid stenting, rates of successful
      reperfusion, sICH, 90-day favourable outcome and mortality were 80% (95% CI 73%
      87%), 7% (95% CI 4%-12%), 53% (95% CI 43%-62%) and 14% (95% CI 9%-19%),
      respectively. CONCLUSIONS: Our data report an association between acute stenting
      and successful reperfusion rates in stroke patients with tandem lesion treated
      with MT. Further studies are warranted to determine the intracranial bleeding
      risk after MT and stenting according to the antiplatelet therapy.

PMID- 29350805
TI  - Is this primip a nullip? The daily abuse of language in obstetrics.

PMID- 29350806
TI  - Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced
      neurtrophil recruitment in vivo.
AB  - Angiotensin-II (Ang-II) has inflammatory activity and is involved in different
      diseases associated with the cardiovascular system. This study has evaluated the
      effect of boldine (B), and two phenanthrene alkaloids semisynthesized by us,
      secoboldine (SB) and boldine methine (BM), on Ang-II-induced neutrophil
      recruitment. Intraperitoneal administration of 1 nM Ang-II induced significant
      neutrophil accumulation, which was maximal at 4-8 h. BM inhibited neutrophil
      infiltration into the peritoneal cavity at 4 h and 8 h by 73% and 77%,
      respectively, SB at 8 h by 55%, and B had no effect on this response. Although BM
      inhibited the release of cytokine-inducible neutrophil
      chemoattractant/keratinocyte-derived chemokine, macrophage inflammatory protein-2
      (MIP-2), and platelet-activating factor (PAF) elicited by Ang-II, SB only reduced
      the release of MIP-2 after 4 h of its administration. Sixty-minute superfusion of
      the rat mesentery with 1 nM Ang-II induced a significant increase in the
      leukocyte-endothelial cell interactions and P-selectin up-regulation, which were
      inhibited by 1 MUM BM and SB. The generation of reactive oxygen species (ROS) in
      endothelial cells stimulated with Ang-II was inhibited significantly by the three
      alkaloids tested. BM also diminished Ang-II-induced interleukin-8 release from
      endothelial cells and blocked the PAF receptor on human neutrophils
      (concentration of the compound needed to produce 50% inhibition value: 28.2 MUM).
      Therefore, BM is a potent inhibitor of Ang-II-induced neutrophil accumulation in
      vivo. This effect appears to be mediated through inhibition of CXC chemokine and
      PAF release, ROS scavenging activity, and blockade of the PAF receptor. Thus, it
      may have potential therapeutic interest for the control of neutrophil recruitment
      that occurs in inflammation associated with elevated levels of Ang-II.

PMID- 29350808
TI  - Errata.

PMID- 29350807
TI  - MAIT cells and viruses.
AB  - Mucosal associated invariant T cells (MAIT cells) bear a T cell receptor (TCR)
      that specifically targets microbially derived metabolites. Functionally, they
      respond to bacteria and yeasts, which possess the riboflavin pathway, essential
      for production of such metabolites and which are presented on MR1. Viruses cannot
      generate these ligands, so a priori, they should not be recognized by MAIT cells
      and indeed this is true when considering recognition through the TCR. However,
      MAIT cells are distinctive in another respect, since they respond quite
      sensitively to non-TCR signals, especially in the form of inflammatory cytokines.
      Thus, a number of groups have shown that virus infection can be "sensed" by MAIT
      cells and a functional response invoked. Since MAIT cells are abundant in humans,
      especially in tissues such as the liver, the question has arisen as to whether
      this TCR-independent MAIT cell triggering by viruses plays any role in vivo. In
      this review, we will discuss the evidence for this phenomenon and some common
      features which emerge across different recent studies in this area.

PMID- 29350810
TI  - Errata.

PMID- 29350809
TI  - CTLA4, T cell function, and long term immunity: an interview with Dr. Mark K.
      Slifka.

PMID- 29350811
TI  - Ascorbate deficiency results in impaired neutrophil apoptosis and clearance and
      is associated with up-regulation of hypoxia-inducible factor 1alpha.
AB  - Some cells, including neutrophils, accumulate high intracellular ascorbate
      concentrations, which suggests that they have an important function in these
      cells. In this study we have used L-gulono-gamma-lactone oxidase (Gulo)-/- mice,
      which are unable to synthesize ascorbate, to generate ascorbate-deficient
      neutrophils and have used these to investigate the effect of ascorbate on
      neutrophil function. Peritoneal neutrophils from ascorbate-deficient animals had
      normal morphology and respiratory burst activity but failed to undergo
      spontaneous apoptosis, determined by morphology and the surface expression of
      phosphatidylserine. Initially, there was increased cell survival, but death
      eventually occurred by necrosis within 48 h. Neutrophils persisted in
      thioglycollate-induced inflammation in Gulo-/R mice with the later appearance of
      necrotic cells, suggesting that apoptosis was also affected in vivo. Also,
      ascorbate-deficient neutrophils were not recognized by macrophages in an in vitro
      assay for phagocytosis, providing further evidence for defective apoptosis and
      clearance. Neutrophils from Gulo-/- mice had elevated levels of hypoxia-inducible
      factor (HIF)-1alpha, a transcription factor regulated by Fe2+ -dependent
      hydroxylases which require ascorbate for optimal activity. HIF-1alpha has been
      shown previously to inhibit neutrophil apoptosis under hypoxic conditions. Our
      results suggest that in ascorbate deficiency, up-regulation of HIF-1alpha blocks
      neutrophil apoptosis under normoxic conditions and that this represents a novel
      and important function for vitamin C in inflammatory cells.

PMID- 29350812
TI  - A unified framework of plant adaptive strategies to drought: Crossing scales and
      disciplines.
AB  - Plant adaptation to drought has been extensively studied at many scales from
      ecology to molecular biology across a large range of model species. However, the
      conceptual frameworks underpinning the definition of plant strategies, and the
      terminology used across the different disciplines and scales are not analogous.
      'Drought resistance' for instance refers to plant responses as different as the
      maintenance of growth and productivity in crops, to the survival and recovery in
      perennial woody or grassland species. Therefore, this paper aims to propose a
      unified conceptual framework of plant adaptive strategies to drought based on a
      revised terminology in order to enhance comparative studies. Ecological
      strategies encapsulate plant adaptation to multidimensional variation in resource
      variability but cannot account for the dynamic and short-term responses to
      fluctuations in water availability. Conversely, several plant physiological
      strategies have been identified along the mono-dimensional gradient of water
      availability in a given environment. According to a revised terminology,
      dehydration escape, dehydration avoidance, dehydration tolerance, dormancy, and
      desiccation tolerance are clearly distinguishable. Their sequential expression is
      expressed as water deficit increases while cavitation tolerance is proposed here
      to be a major hydraulic strategy underpinning adaptive responses to drought of
      vascular plants. This continuum of physiological strategies can be interpreted in
      the context of the ecological trade-off between water-acquisition vs. water
      conservation, since growth maintenance is associated with fast water use under
      moderate drought while plant survival after growth cessation is associated with
      slow water use under severe drought. Consequently, the distinction between
      'drought resistance' and 'drought survival', is emphasized as crucial to ensure a
      correct interpretation of plant strategies since 'knowing when not to grow' does
      not confer 'drought resistance' but may well enhance 'drought survival'. This
      framework proposal should improve cross-fertilization between disciplines to help
      tackle the increasing worldwide challenges that drought poses to plant
      adaptation.

PMID- 29350814
TI  - IL-5-mediated eosinophil survival requires inhibition of GSK-3 and correlates
      with beta-catenin relocalization.
AB  - Interleukin (IL)-5 is a hematopoietic cytokine able to regulate differentiation,
      survival, and effector functions of eosinophils. It binds specifically to its
      receptor, which is composed of a cytokine-specific alpha-chain and a beta-chain
      shared with the receptors for IL-3 and the granulocyte macrophage-colony
      stimulating factor. The molecular mechanisms by which IL-5 modulates eosinophil
      survival remain unclear. In this study, we demonstrate that IL-5 withdrawal
      induces eosinophil apoptosis through a mitochondria-dependent pathway,
      independently of Fas receptor activation. The lipid kinase phosphatidylinositol-3
      kinase plays a crucial role in the maintenance of eosinophil survival, as
      inhibition of its activity results in apoptosis. IL-5 induces phosphorylation and
      thus, inhibition of the Forkhead transcription factor FOXO3a and glycogen
      synthase kinase 3 (GSK-3). We analyzed expression of FOXO3a-dependent
      transcriptional targets: Fas ligand or Bim (a proapoptotic Bcl-2 family member),
      but neither was detected in apoptotic eosinophils. We further show that GSK-3 is
      activated after IL-5 withdrawal, and inhibition of its activity rescues
      eosinophils from apoptosis. beta-catenin, a direct GSK-3 substrate, is present in
      the nucleus of IL-5-stimulated eosinophils, but it is translocated to the plasma
      membrane in the absence of cytokine in a GSK-3-dependent manner. This is the
      first report describing a potential role for GSK-3 and beta-catenin in regulating
      eosinophil survival and suggests a novel mechanism by which IL-5 inhibits the
      constitutive apoptotic program in these cells.

PMID- 29350816
TI  - Interview with Dr. Paul Guyre and Mr. Lehn Weaver regarding Pivotal Advance:
      Activation of cell surface Toll-like receptors causes shedding of the hemoglobin
      scavenger receptor CD163.

PMID- 29350817
TI  - In response to Faas et al.

PMID- 29350818
TI  - Aggregation of beta2 integrins activates human neutrophils through the IkappaB/NF
      kappaB pathway.
AB  - Neutrophils are now considered central to the pathogenesis of most forms of acute
      lung injury. Neutrophils do not cause damage while suspended in the bloodstream;
      however, a release of cytotoxic agents occurs when neutrophils are adherent to
      endothelium, epithelium, or extracellular matrix proteins in the interstitium.
      Such neutrophil adherence is mediated predominantly through beta2 integrins
      (CD11/CD18) on its surface. This study was undertaken to investigate whether the
      IkappaB/nuclear factor (NF)-kappaB cascade is involved in this beta2 integrin
      mediated activation of human neutrophils. beta2 Integrin Mac-1 (CD11b/CD18)
      aggregation was induced by antibody cross-linking of the integrins on the cell
      surface. beta2 Integrin aggregation induced interleukin-1beta and tumor necrosis
      factor-alpha production, which suggests the activation of neutrophils by beta2
      integrin. IkappaBalpha was markedly degraded at 1 h, and NF-kappaB-DNA-binding
      activity markedly increased 2 h after beta2 integrin aggregation, which activated
      IkappaB kinase activity at 1 h. beta2 Integrin-induced cytokine production was
      suppressed by MG132 or SN50 pretreatment, which blocked the activation of NF
      kappaB. These findings suggest that the activation of human neutrophils by beta2
      integrin aggregation is mediated through the activation of the IkappaB/NF-kappaB
      pathway.

PMID- 29350821
TI  - Interview with Dr. Andrew Issekutz regarding Pivotal Advance: Endothelial growth
      factors VEGF and bFGF differentially modulate monocyte and neutrophil recruitment
      to inflammation.

PMID- 29350820
TI  - Errata.

PMID- 29350822
TI  - Resveratrol Suppresses Rotenone-induced Neurotoxicity Through Activation of
      SIRT1/Akt1 Signaling Pathway.
AB  - Rotenone is a common pesticide and has been reported as one of the risk factors
      for Parkinson disease. Rotenone can cause neuronal death or apoptosis through
      inducing oxidative injury and inhibiting mitochondrial function. As a natural
      polyphenolic compound, resveratrol possesses the antioxidant capacity and
      neuroprotective effect. However, the mechanism underlying the neuroprotective
      effect of resveratrol against rotenone-induced neurotoxicity remains elusive.
      Here, we treated PC12 cells with rotenone to induce neurotoxicity, and the
      neurotoxic cells were subjected to resveratrol treatment. The CCK8 and LDH
      activity assays demonstrated that resveratrol could suppress neurotoxicity
      induced by rotenone (P < 0.01). The DCFH-DA assay indicated that resveratrol
      reduced the production of reactive oxygen species (ROS). JC-1 and Hoechst
      33342/PI staining revealed that resveratrol attenuated mitochondrial dysfunction
      and cell apoptosis. Moreover, resveratrol reversed rotenone-induced decrease in
      SIRT1 expression and Akt1 phosphorylation (P < 0.05). Furthermore, when the SIRT1
      and Akt1 activity was inhibited by niacinamide and LY294002, respectively, the
      neuroprotective effect of resveratrol was remarkably attenuated, which implied
      that SIRT1 and Akt1 could mediate this process and may be potential molecular
      targets for intervening rotenone-induced neurotoxicity. In summary, our study
      demonstrated that resveratrol reduced rotenone-induced oxidative damage, which
      was partly mediated through activation of the SIRT1/Akt1 signaling pathway. Our
      study launched a promising avenue for the potential application of resveratrol as
      a neuroprotective therapeutic agent in Parkinson disease. Anat Rec, 301:1115
      1125, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29350823
TI  - Interview with Dr. Philip Griebel regarding Pivotal Advance: Passively acquired
      membrane proteins alter the functional capacity of bovine polymorphonuclear
      cells.

PMID- 29350824
TI  - Rational design of MyD88 inhibitors-new pathways to inflammatory control: an
      interview with Dr. Claudio Sette.

PMID- 29350825
TI  - ANG II facilitated CD11+ Ly6Chi cells reprogramming into M1-like macrophage
      through Erk1/2 or p38-Stat3 pathway and involved in EAM.
AB  - Macrophage, a highly plastic population, is widely distributed. Macrophage
      functions are settled and acquired polarization programs in response to
      microenvironmental signals and involved in many inflammatory disorders, such as
      experimental autoimmune myocarditis (EAM). Phenotypic and functional changes in
      macrophage are considered as an important determinant of disease progression
      and/or regression. Angiotensin II (ANG II), as a powerful proinflammatory factor,
      plays critical roles in inflammatory diseases and macrophage recruitment. It
      remains unclear whether ANG II contributed to the functional skewing of cardiac
      infiltrated monocytes/macrophage and involved in EAM development. Therefore, the
      present work was to address the above questions. Our data showed that ANG II
      contributed to CD11b+ Ly6Chi (CD11b+ Ly6G- Ly6C+ ) cells reprogramming into M1
      like macrophage through Erk1/2 or p38/Stat3 pathway and the reprogramming M1-like
      cells promoted Th17 cells expansion; abrogation of ANG II-AT1 R axis
      significantly ameliorated cardiac injury. The present work first demonstrated a
      novel immune regulation role of ANG II; ANG II, as a powerful immune factor,
      promoted CD11b+ Ly6Chi inflammatory cells reprogramming into M1-like macrophage
      and involved in inflammatory disorders development; our results also indicated
      that ANG II may be a potential therapeutic target for inflammatory diseases.

PMID- 29350826
TI  - Dispersal and population state of an endangered island lizard following a
      conservation translocation.
AB  - Population size is widely used as a unit of ecological analysis, yet to estimate
      population size requires accounting for observed and latent heterogeneity
      influencing dispersion of individuals across landscapes. In newly established
      populations, such as when animals are translocated for conservation, dispersal
      and availability of resources influence patterns of abundance. We developed a
      process to estimate population size using N-mixture models and spatial models for
      newly established and dispersing populations. We used our approach to estimate
      the population size of critically endangered St. Croix ground lizards (Ameiva
      polops) five years after translocation of 57 individuals to Buck Island, an
      offshore island of St. Croix, United States Virgin Islands. Estimates of
      population size incorporated abiotic variables, dispersal limits, and operative
      environmental temperature available to the lizards to account for low species
      detection. Operative environmental temperature and distance from the
      translocation site were always important in fitting the N-mixture model
      indicating effects of dispersal and species biology on estimates of population
      size. We found that the population is increasing its range across the island by 5
      10% every six months. We spatially interpolated site-specific abundance from the
      N-mixture model to the entire island, and we estimated 1,473 (95% CI, 940-1,802)
      St. Croix ground lizards on Buck Island in 2013 corresponding to survey results.
      This represents a 26-fold increase since the translocation. We predicted the
      future dispersal of the lizards to all habitats on Buck Island, with the
      potential for the population to increase by another five times in the future.
      Incorporating biologically relevant covariates as explicit parameters in
      population models can improve predictions of population size and the future
      spread of species introduced to new localities.

PMID- 29350828
TI  - Differential expression of beta2 -integrins and cytokine production between
      gammadelta and alphabeta T cells in experimental autoimmune encephalomyelitis.
AB  - The expression of beta2 -integrins on gammadelta T cells in naive mice or those
      with experimental autoimmune encephalomyelitis (EAE) remains poorly
      characterized. We compared beta2 -integrin expression and cytokine production
      between gammadelta and alphabeta T cells over the acute course of EAE. We
      observed that unlike in alphabeta T cells, beta2 -integrin expression on
      gammadelta T cells increased significantly from baseline, peaked at Day 10, and
      remained unchanged in the draining lymph nodes or declined in the spleen and CNS
      by Day 15. In addition, IFN-gamma- and TNF-alpha-producing gammadelta T cells
      infiltrated the CNS rapidly and produced significantly more of these cytokines
      than alphabeta T cells throughout the course of EAE. These results suggest unique
      roles for beta2 -integrins in the trafficking of gammadelta versus alphabeta T
      cells during EAE and that gammadelta T cells infiltrate the CNS rapidly,
      producing cytokines, which modulate acute disease.

PMID- 29350829
TI  - TGF-beta down-regulates IL-1alpha-induced TLR2 expression in murine hepatocytes.
AB  - We have previously reported that the proinflammatory cytokine interleukin (IL)
      1alpha can up-regulate functional Toll-like receptor 2 (TLR2) expression in
      primary-cultured murine hepatocytes, and bacterial lipopeptide (BLP) is capable
      of signaling through TLR2 to induce serum amyloid A (SAA) expression in
      hepatocytes. In the present study, we investigated the effect of the anti
      inflammatory cytokine transforming growth factor-beta (TGF-beta) on TLR2
      expression in primary-cultured murine hepatocytes. At the mRNA and protein
      levels, TGF-beta up-regulated TLR2 expression but inhibited TLR2 expression
      induced by IL-1alpha at 24 h. BLP-induced SAA promoter activity could be
      augmented by pretreatment with IL-1alpha but not TGF-beta or the combination of
      TGF-beta and IL-1alpha. TLR2 promoter activity and nuclear factor (NF)-kappaB
      activation by IL-1alpha were inhibited by TGF-beta treatment. Pretreatment with
      TGF-beta strongly suppressed IL-1alpha-induced TLR2 promoter activity and NF
      kappaB activation, which was consistent with the down-regulation of type I IL-1
      receptor (IL-1RI) mRNA expression. IL-1alpha up-regulated IL-1RI mRNA, but it was
      inhibited by the treatment with TGF-beta. These results suggest that TGF-beta
      suppresses the induction of TLR2 expression by IL-1alpha through down-regulation
      of IL-1RI expression. These results also demonstrate the disparity between IL
      1alpha and TGF-beta in regulating TLR2-mediated SAA production in hepatocytes.

PMID- 29350830
TI  - Erratum.

PMID- 29350831
TI  - Randomized trial on extended versus modified right lobe grafts in living donor
      liver transplantation.
AB  - Despite advances in the practice of living donor liver transplantation (LDLT),
      the optimum surgical approach with respect to the middle hepatic vein (MHV) in
      right lobe LDLT remains undefined. We designed a randomized trial to compare the
      early postoperative outcomes in recipients and donors between extended right lobe
      grafts (ERGs; transection plane was maintained to the left of MHV and division of
      MHV performed beyond the segment VIII vein) and modified right lobe grafts (MRGs;
      transection plane was maintained to the right of MHV; the segment V and VIII
      drainage was reconstructed using a conduit of recipient portal vein). Eligible
      patients (n = 86) were prospectively randomized into the ERG arm (n = 43) and the
      MRG arm (n = 43) at the beginning of donor hepatectomy. The primary endpoint
      considered in this equivalence trial was patency of the MHV or the reconstructed
      "neo-MHV" in the recipient. The secondary endpoints included biochemical
      parameters, postoperative complications, mortality in recipients as well as
      donors and volume regeneration of remnant liver in donors, measured at 2 months.
      The patency of the MHV was comparable in the ERG and MRG arms (90.7% versus
      81.4%; difference, 9.3%; 95% confidence interval [CI], -5.8 to 24.4; z score,
      1.245; P = 0.21). Volume regeneration of the remnant liver in donors was
      significantly better in the MRG arm (111.3% versus 87.3%; mean difference, 24%;
      95% CI, 14.6-33.3; P < 0.001). The remaining secondary endpoints in donors and
      recipients were similar between the 2 arms. To conclude, MRG with reconstructed
      neo-MHV has comparable patency to native MHV in ERG and confers equivalent graft
      outflow in the recipient. Furthermore, it allows better remnant liver
      regeneration in the donor at 2 months. Liver Transplantation 24 888-896 2018
      AASLD.

PMID- 29350832
TI  - The developmental trinity of mind: Cognizance, executive control, and reasoning.
AB  - This paper summarizes research on how cognizance, that is, awareness of mental
      processes, interacts with executive control and reasoning from childhood to
      adolescence. Central positions are that (a) cognizance changes extensively with
      age; (b) it contributes to the formation of executive control, and (c) mediates
      between executive control and reasoning. Cognizance recycles with changes in
      executive and inferential possibilities in four developmental cycles: it
      registers their present state, yielding insight into their operation, allowing
      their better management; this catalyzes their transformation into the next level.
      Implications for theory of intellectual development and practical implications
      for education are discussed. This article is categorized under: Psychology >
      Development and Aging Neuroscience > Cognition Neuroscience > Development
      Philosophy > Consciousness.

PMID- 29350833
TI  - Platelets kill bacteria by bridging innate and adaptive immunity via platelet
      factor 4 and FcgammaRIIA.
AB  - : Essentials Human platelets specifically interact with IgG opsonized bacteria
      through FcgammaRIIA. Platelet factor 4 (PF4) binds to polyanions (P) and
      undergoes a conformational change. Anti-PF4/P IgG opsonizes PF4-coated Gram
      positive and Gram-negative bacteria. Platelets specifically kill E.coli opsonized
      with PF4 and human anti-PF4/P IgG. SUMMARY: Background Activated platelets
      release the chemokine platelet factor 4 (PF4) stored in their granules. PF4 binds
      to polyanions (P) on bacteria, undergoes a conformational change and exposes
      neoepitopes. These neoepitopes induce production of anti-PF4/P antibodies. As PF4
      binds to a variety of bacteria, anti-PF4/P IgG can bind and opsonize several
      bacterial species. Objective Here we investigated whether platelets are able to
      kill bacteria directly after recognizing anti-PF4/P IgG opsonized bacteria in the
      presence of PF4 via their FcgammaRIIA. Methods Using platelet-bacteria suspension
      co-culture experiments and micropatterns with immobilized viable bacteria, in
      combination with pharmacological inhibitors and human anti- PF4/P IgG we analyzed
      the role of platelet-mediated killing of bacteria. Results In the presence of
      PF4, human anti-PF4/P IgG and platelets, E. coli killing (> 50%) with colony
      forming units (CFU mL-1 ) 0.71 * 104 +/- 0.19 was observed compared with controls
      incubated only with anti-PF4/P IgG (CFU mL-1 3.4 * 104 +/- 0.38). Blocking of
      platelet FcgammaRIIA using mAb IV.3 (CFU mL-1 2.5 * 104 +/- 0.45), or integrin
      alphaIIbbeta3 (CFU mL-1 2.26 * 104 +/- 0.31), or disruption of cytoskeletal
      functions (CFU mL-1 2.7 * 104 +/- 0.4) markedly reduced E. coli killing by this
      mechanism. Our observation of E. coli killing by platelets on micropatterned
      arrays is compatible with the model that platelets kill bacteria by covering
      them, actively concentrating them into the area under their granulomere and then
      releasing antimicrobial substances of platelet alpha-granules site directed
      towards bacteria. Conclusion These findings collectively indicate that by
      bridging of innate and adaptive immune mechanisms, platelets and anti
      PF4/polyanion antibodies cooperate in an antibacterial host response.

PMID- 29350834
TI  - Proton-pump inhibitors elevate infection rate in cardiothoracic surgery patients
      by influencing PMN function in vitro and in vivo.
AB  - Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid
      suppressive agents that belong to the world's most sold medication. However, they
      are pronounced to have immunosuppressive aspects. In our study, a negative
      influence of PPI on functions of polymorphonuclear cells in vitro like
      phagocytosis, oxidative burst, chemotaxis, and killing activity was shown,
      whereas formation of neutrophil extracellular traps (NET)osis remained
      unaffected. Pantoprazole stimulation additionally reduced the production of the
      proinflammatory cytokine IL-1beta in whole blood assay as well as the production
      of IL-2 and IFN-gamma after whole blood stimulation with phytohaemagglutinin.
      Moreover, IFN-gamma feedback mechanisms and signaling by STAT-1 was impaired by
      PPI. Cardiac surgery is accompanied by developing systemic inflammatory response
      syndrome with immunosuppressive aspects. We exhibited reduced oxidative burst
      analyzing cardiac surgery patients' samples receiving or not receiving PPI.
      Furthermore, a higher rate of infections in patients receiving permanent PPI
      medication in retrospective analysis was uncovered. Patients undergoing cardiac
      surgery with cardiopulmonary bypass and regular PPI medication developed
      significant more infections retrospectively indicating a clinical impact of the
      immunosuppressive influence of PPI.

PMID- 29350835
TI  - Comment on "Neutrophils: are they hyperalgesic or anti-hyperalgesic?"

PMID- 29350836
TI  - Interview with Dr. Yoshiro Kobayashi regarding Pivotal Advance: A suppressive
      role of nitric oxide in MIP-2 production by macrophages upon coculturing with
      apoptotic cells.

PMID- 29350838
TI  - Toll-like receptors, endogenous ligands, and constitutive control (or, why I'm
      still standing at the podium): an interview with Dr. Jeffrey L. Platt.

PMID- 29350839
TI  - Endocannabinoids, cannabinoid receptors and inflammatory stress: an interview
      with Dr. Pal Pacher.

PMID- 29350840
TI  - A phase 3 trial of mometasone furoate sinus implants for chronic sinusitis with
      recurrent nasal polyps.
AB  - BACKGROUND: Topical intranasal corticosteroid sprays (INCSs) are standard
      treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient
      compliance and impaired access of drug to the sinus mucosa. A corticosteroid
      eluting sinus implant was designed to address these limitations in patients with
      recurrent polyposis after sinus surgery by delivering 1350 MUg of mometasone
      furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days.
      METHODS: A randomized, sham-controlled, double-blind trial was undertaken in 300
      adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were
      candidates for repeat surgery. Eligible patients were randomized (2:1) and
      underwent in-office bilateral placement of 2 implants or a sham procedure. All
      patients used the MF INCS 200 MUg once daily. Co-primary efficacy endpoints were
      the change from baseline in nasal obstruction/congestion score and bilateral
      polyp grade, as determined by an independent panel based on centralized, blinded
      videoendoscopy review. RESULTS: Patients treated with implants experienced
      significant reductions in both nasal obstruction/congestion score (p = 0.0074)
      and bilateral polyp grade (p = 0.0073) compared to controls. At day 90, implants
      were also associated with significant reductions in 4 of 5 prespecified secondary
      endpoints compared to control: proportion of patients still indicated for repeat
      sinus surgery (p = 0.0004), percent ethmoid sinus obstruction (p = 0.0007), nasal
      obstruction/congestion (p = 0.0248), and decreased sense of smell (p = 0.0470),
      but not facial pain/pressure (p = 0.9130). One patient experienced an implant
      related serious adverse event (epistaxis). CONCLUSION: Significant improvements
      over a range of subjective and objective endpoints, including a reduction in the
      need for sinus surgery by 61%, suggest that MF sinus implants may play an
      important role in management of recurrent NP.

PMID- 29350841
TI  - Epidemiology and molecular characterization of influenza viruses in Burkina Faso,
      sub-Saharan Africa.
AB  - BACKGROUND: The importance of influenza viruses in respiratory infections in sub
      Saharan Africa has been historically overlooked, including in Burkina Faso.
      OBJECTIVES: This study therefore aimed at evaluating the prevalence and seasonal
      occurrence of influenza viruses in children under 5 years old, at risk of
      influenza-related complications, presenting with influenza-like illness (ILI) or
      severe acute respiratory infection (SARI). The study also aimed at identifying
      the periods with increased influenza transmission for vaccination recommendations
      in Burkina Faso. METHODS: From January 2014 to December 2015, ILI and SARI (2015
      only) patients were recruited in six healthcare centers in Burkina Faso.
      Influenza A and B molecular detection and subtyping were performed. Clade
      clustering of a subset of A(H1N1)pdm09 and A(H3N2) strains was deduced by
      performing phylogenetic analyses on hemagglutinin gene sequences. Weekly
      surveillance data from FluNet (2011-2013; 2016) and this study (2014-2015) were
      used to identify periods of increased influenza activity. RESULTS: Influenza A
      and B viruses were detected in 15.1% (112 of 743) of ILI and 6.6% (12 of 181) of
      SARI patients. Overall, influenza A viruses were largely predominant (81 of 124,
      65.3%), with 69.1% of A(H3N2) and 30.9% of A(H1N1)pdm09 strains. Four waves of
      increased transmission were identified in 2014-2015, each dominated by different
      influenza subtypes and clades. Between 2011 and 2016, periods of increased
      influenza activity varied in their frequency, duration, and timing. CONCLUSION:
      Influenza A and B viruses were detected in a substantial number of ILI and SARI
      cases in Burkina Faso. Vaccination in September-October would likely protect the
      highest number of patients.

PMID- 29350842
TI  - From grey to green: Efficacy of eco-engineering solutions for nature-based
      coastal defence.
AB  - Climate change is increasing the threat of erosion and flooding along coastlines
      globally. Engineering solutions (e.g. seawalls and breakwaters) in response to
      protecting coastal communities and associated infrastructure are increasingly
      becoming economically and ecologically unsustainable. This has led to
      recommendations to create or restore natural habitats, such as sand dunes,
      saltmarsh, mangroves, seagrass and kelp beds, and coral and shellfish reefs, to
      provide coastal protection in place of (or to complement) artificial structures.
      Coastal managers are frequently faced with the problem of an eroding coastline,
      which requires a decision on what mitigation options are most appropriate to
      implement. A barrier to uptake of nature-based coastal defence is stringent
      evaluation of the effectiveness in comparison to artificial protection
      structures. Here, we assess the current evidence for the efficacy of nature-based
      vs. artificial coastal protection and discuss future research needs. Future
      projects should evaluate habitats created or restored for coastal defence for
      cost-effectiveness in comparison to an artificial structure under the same
      environmental conditions. Cost-benefit analyses should take into consideration
      all ecosystem services provided by nature-based or artificial structures in
      addition to coastal protection. Interdisciplinary research among scientists,
      coastal managers and engineers is required to facilitate the experimental trials
      needed to test the value of these shoreline protection schemes, in order to
      support their use as alternatives to artificial structures. This research needs
      to happen now as our rapidly changing climate requires new and innovative
      solutions to reduce the vulnerability of coastal communities to an increasingly
      uncertain future.

PMID- 29350843
TI  - Divergent expression and function of glucocorticoid receptor beta in human
      monocytes and T cells.
AB  - Glucocorticoid (GC) insensitivity is a significant problem in the treatment of
      immune-mediated diseases. The current study examined whether T cells and
      monocytes differed in their response to GC and the potential molecular basis for
      their variation in response to steroids. Functional studies revealed that
      dexamethasone (DEX) inhibited phorbol 12-myristate 13-acetate/ionomycin-induced
      tumor necrosis factor alpha and interleukin-6 production to a significantly
      lesser extent in monocytes than T cells. In parallel, a significantly longer
      period of time was required for DEX to induce the steroid-responsive gene,
      mitogen-activated protein kinase phosphatase-1 (MKP-1), in human monocytes as
      compared with T cells. It is interesting that such differences were not observed
      between murine T cells and monocytes. GC receptor beta (GCRbeta) is a splicing
      variant of the classic GCR, GCRalpha, which functions as a dominant-negative
      inhibitor of GCRalpha in humans, not mice (as mice do not express GCRbeta mRNA as
      a result of a difference in the murine GCR 9b exon sequence). It was found that
      human monocytes had a significantly higher level of GCRbeta than T cells.
      Furthermore, GCRbeta was found in the cytoplasm and nucleus of monocytes, and
      GCRbeta was localized to the nucleus of T cells. This raised the possibility that
      GCRbeta in the cytoplasm could affect GCRalpha cellular shuttling in response to
      DEX. Indeed, we found that DEX-induced nuclear translocation of GCRalpha was
      decreased in monocytes as compared with T cells. Specific RNA silencing of
      GCRbeta in human monocytes resulted in enhanced steroid-induced GCRalpha
      transactivation and transrepression. Our data suggest that GCRbeta contributes to
      variation in the GC responses of monocytes versus T cells.

PMID- 29350844
TI  - Unfair to ignore long-established line of published research.

PMID- 29350846
TI  - Vasoactive intestinal peptide, periodontal disease, and the innate immune
      response: an interview with Dr. John J. Taylor.

PMID- 29350847
TI  - Massive, sustained gammadelta T cell migration from the bovine skin in vivo.
AB  - In all species studied so far, gammadelta T cells are abundantly present in
      epithelia. The functions of these cells are largely unknown. Using a lymph duct
      cannulation method, which is only possible in large animals such as cattle, we
      show that large numbers of gammadelta T cells, but not alphabeta T cells, are
      constitutively present in pseudoafferent lymph draining bovine skin. The
      gammadelta T cells, which are present in pseudoafferent lymph, use Vgamma
      segments that are characteristic for bovine dermal gammadelta T cells, suggesting
      that these cells migrated from the skin. Further supporting the origin of these
      cells is the fact that fluorescent latex beads injected in the skin could be
      recovered in cells in the pseudoafferent lymph. The cannulation method is
      minimally invasive, and the lymph flow, which was sustained and remained
      essentially unaltered during 14 days, closely represents the in vivo situation.
      The gammadelta T cells could not be induced to produce IFN-gamma, TNF-alpha, and
      IL-10, and they did not express costimulatory molecules, IL-2 receptor, and MHC
      Class II molecules. The level of gammadelta T cell egress was 6.7 * 103
      gammadelta T cells per cm2 skin per hour, which is enough to deplete all
      gammadelta T cells from the skin within 46 h. As this massive gammadelta T cell
      migration was observed during 14 days, constant replenishment of these cells must
      take place. Our data suggest that gammadelta T cells in tissues fulfill more than
      exclusively local functions.

PMID- 29350848
TI  - Response to "Unfair to ignore long-established line of published research".

PMID- 29350849
TI  - The Shwartzman reaction repealed.

PMID- 29350850
TI  - Macrophage biology and immunology: man is not a mouse.

PMID- 29350852
TI  - TRAF6 distinctively mediates MyD88- and IRAK-1-induced activation of NF-kappaB.
AB  - MyD88 and IL-1R-associated kinase 1 (IRAK-1) play crucial roles as adaptor
      molecules in signal transduction of the TLR/IL-1R superfamily, and it is known
      that expression of these proteins leads to the activation of NF-kappaB in a TNFR
      associated factor 6 (TRAF6)-dependent manner. We found in this study, however,
      that a dominant-negative mutant of TRAF6, lacking the N-terminal RING and zinc
      finger domain, did not inhibit IRAK-1-induced activation of NF-kappaB in human
      embryonic kidney 293 cells, although the TRAF6 mutant strongly suppressed the
      MyD88-induced activation. The dominant-negative mutant of TRAF6 did not affect
      the IRAK-1-induced activation, regardless of the expression level of IRAK-1. In
      contrast, small interfering RNA silencing of TRAF6 expression inhibited MyD88
      induced and IRAK-1-induced activation, and supplementation with the TRAF6
      dominant-negative mutant did not restore the IRAK-1-induced activation.
      Expression of IRAK-1, but not MyD88, induced the oligomerization of TRAF6, and
      IRAK-1 and the TRAF6 dominant-negative mutant were associated with TRAF6. These
      results indicate that TRAF6 is involved but with different mechanisms in MyD88
      induced and IRAK-induced activation of NF-kappaB and suggest that TRAF6 uses a
      distinctive mechanism to activate NF-kappaB depending on signals.

PMID- 29350854
TI  - HMGB1 preconditioning: therapeutic application for a danger signalo.
AB  - High mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as
      a late mediator of lethality in sepsis and as an early mediator of inflammation
      following injury. In contrast to the proinflammatory role of HMGB1, recent
      evidence suggests beneficial applications of HMGB1 in injury states. One such
      application is the use of HMGB1 as a preconditioning stimulus. Preconditioning is
      a phenomenon whereby a low level of stressful stimuli confers protection against
      subsequent injury. Preconditioning has been demonstrated in multiple species, can
      be induced by various stimuli, and is applicable in different organ systems. Only
      with the recent introduction of the concept of endogenous molecules, such as
      HMGB1, as signals and mediators for inflammation during injury states has the use
      of endogenous molecules been investigated for this use. This review will focus on
      the use of endogenous molecules, specifically HMGB1, as a preconditioning
      stimulus and its mechanism of protection, as well as other protective
      applications for HMGB1.

PMID- 29350853
TI  - Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced
      inflammatory responses to influenza A/PR/8/34 in the absence and presence of
      Delta9 -tetrahydrocannabinol.
AB  - We have previously reported that Delta-9-tetrahydrocannabinol (Delta9 -THC)
      treated mice challenged with influenza virus A/PR/8/34 (PR8) developed increased
      viral hemagglutinin 1 (H1) mRNA levels and decreased monocyte and lymphocyte
      recruitment to the pulmonary airways when compared with mice challenged with PR8
      alone. The objective of the present study was to examine the role of cannabinoid
      (CB1 /CB2 ) receptors in mediating the effects of Delta9 -THC on immune and
      epithelial cell responses to PR8. In the current study, Delta9 -THC-treated CB1
      /CB2 receptor null (CB1-/- /CB2-/- ) and wild-type mice infected with PR8 had
      marked increases in viral H1 mRNA when compared with CB1-/- /CB2-/- and wild-type
      mice challenged with PR8 alone. However, the magnitude of the H1 mRNA levels was
      greatly reduced in CB1-/- /CB2-/- mice as compared with wild-type mice. In
      addition, Delta9 -THC-treated CB1-/- /CB2-/- mice infected with PR8 had increased
      CD4+ T cells and IFN-gamma in bronchoalveolar lavage fluid with greater pulmonary
      inflammation when compared with Delta9 -THC-treated wild-type mice infected with
      PR8. Delta9 -THC treatment of CB1-/- /CB2-/- mice in the presence or absence of
      PR8 challenge also developed greater amounts of mucous cell metaplasia in the
      affected bronchiolar epithelium. Collectively, the immune and airway epithelial
      cell responses to PR8 challenge in Delta9 -THC-treated CB1-/- /CB2-/- and wild
      type mice indicated the involvement of CB1 /CB2 receptor-dependent and 
      independent mechanisms.

PMID- 29350855
TI  - Measurement properties of gingival biotype evaluation methods.
AB  - BACKGROUND: There are numerous methods to measure the dimensions of the gingival
      tissue, but few have compared the effectiveness of one method over another.
      OBJECTIVE: This study aimed to describe a new method and to estimate the validity
      of gingival biotype assessment with the aid of computed tomography scanning
      (CTS). MATERIALS AND METHODS: In each patient different methods of evaluation of
      the gingival thickness were used: transparency of periodontal probe,
      transgingival, photography, and a new method of CTS). Intrarater and interrater
      reliability considering the categorical classification of the gingival biotype
      were estimated with Cohen's kappa coefficient, intraclass correlation coefficient
      (ICC), and ANOVA (P < .05). The criterion validity of the CTS was determined
      using the transgingival method as the reference standard. Sensitivity and
      specificity values were computed along with theirs 95% CI. RESULTS: Twelve
      patients were subjected to assessment of their gingival thickness. The highest
      agreement was found between transgingival and CTS (86.1%). The comparison between
      the categorical classifications of CTS and the transgingival method (reference
      standard) showed high specificity (94.92%) and low sensitivity (53.85%) for
      definition of a thin biotype. CONCLUSION: The new method of CTS assessment to
      classify gingival tissue thickness can be considered reliable and clinically
      useful to diagnose thick biotype.

PMID- 29350856
TI  - Interview with Dr. Nancy A. Lee and Dr. James J. Lee regarding Pivotal Advance:
      Eosinophil infiltration of solid tumors is an early and persistent inflammatory
      host response.

PMID- 29350858
TI  - Novel interferon-beta-induced gene expression in peripheral blood cells.
AB  - Type I IFNs are used for treating viral, neoplastic, and inflammatory disorders.
      The protein products encoded by IFN-stimulated genes (ISGs) likely mediate
      clinical effects of IFN in patients. Macroarray assays, used for studying ISG
      induction in IFN-treated patients, comprise genes identified predominantly
      through analysis of long-term cell lines. To discover genes induced selectively
      by IFN-beta in PBMC, we exposed whole blood to physiological concentrations of
      IFN-beta. PBMC were prepared, and RNA was extracted, reverse-transcribed, and
      hybridized to cDNA microarrays, and microarray analysis identified 39 ISGs and 20
      IFN-repressed genes (IRGs). Thirty-three ISGs were known previously, and six ISGs
      were novel. New ISGs included GTP cyclohydrolase 1; hypothetical protein
      LOC129607; hypothetical protein FLJ38348; leucine aminopeptidase 3; squalene
      epoxidase; and GTP-binding protein overexpressed in skeletal muscle. Twenty IRGs
      included IL-1beta and CXCL8, which had been identified earlier. CXCL1 was a novel
      IRG identified in the current study. PCR analysis demonstrated the regulation of
      six novel ISGs and CXCL1 as an IRG in PBMC and astrocytoma cells. Results were
      validated using RNA obtained ex vivo from blood of patients after injection with
      IFN-beta. Identification of new ISGs and IRGs in primary PBMC will enhance
      macroarray assays for monitoring IFN responsiveness.

PMID- 29350860
TI  - Macrophages, apoptotic cells and cholesterol-strategies for survival: an
      interview with Dr. Ira Tabas.

PMID- 29350862
TI  - Erratum.

PMID- 29350861
TI  - Expression of the heparan sulfate-degrading enzyme heparanase is induced in
      infiltrating CD4+ T cells in experimental autoimmune encephalomyelitis and
      regulated at the level of transcription by early growth response gene.
AB  - The heparan sulfate-cleaving enzyme heparanase (HPSE) plays an important role in
      remodeling of the basement membrane and extracellular matrix during inflammation.
      Inducible HPSE enzymatic activity has been reported in leukocytes; however,
      little is known of the molecular mechanisms that regulate HPSE gene expression
      during inflammatory disease. In this study, HPSE expression and regulation in the
      T cell-mediated disease model, experimental autoimmune encephalomyelitis (EAE),
      were investigated. Expression analysis showed that HPSE mRNA is induced in rat
      CD4+ antigen-specific T lymphocytes upon activation and correlates with the
      encephalitogenicity of the cells. Examination of the kinetics and cell type
      specific expression of HPSE throughout the progression of active EAE in rats,
      indicated that HPSE was highly expressed in CD4+ T cells infiltrating the central
      nervous system (CNS) during clinical disease. Little or no HPSE expression was
      observed in CD8+ T cells, macrophages, or astrocytes during disease progression.
      To investigate the mechanism of inducible HPSE gene regulation in T cells,
      studies were extended into human primary T cells. HPSE mRNA, protein, and
      enzymatic activity were induced upon activation. Functional analysis of the human
      HPSE promoter identified an EGR1 binding motif that contained high inducible
      activity and was transactivated by EGR1. Furthermore, the treatment of primary T
      lymphocytes with an EGR1 siRNA inhibited inducible HPSE mRNA expression. These
      data provide evidence to suggest that inducible HPSE expression in primary T
      lymphocytes is regulated at the transcriptional level by EGR1 and is important in
      facilitating CD4+ T cell infiltration into the CNS to promote EAE.

PMID- 29350863
TI  - Chemokine stromal cell-derived factor-1 induction by C/EBPbeta activation is
      associated with all-trans-retinoic acid-induced leukemic cell differentiation.
AB  - Stromal cell-derived factor-1 (SDF-1/CXCL12) is one of the essential chemokines,
      which mediates hematopoietic differentiations. However, the mechanism by which
      SDF-1 expression is regulated in granulocyte differentiation is poorly
      understood. Here, we suggest a novel mechanism by which all-trans-retinoic acid
      (ATRA) induces the expression of SDF-1 during the differentiation of
      promyelomonocytic leukemic U937 cells. Moreover, we also demonstrate that
      activation of transcription factor C/EBPbeta by ATRA regulates SDF-1 expression
      in U937 cells. In addition, we show that the cyclin-dependent kinase inhibitors
      p21WAF1/CIP1 and Pyk2 are up-regulated by SDF-1 and increased markedly by the
      costimulation of ATRA and SDF-1. Furthermore, ATRA and SDF-1alpha additively
      induce U937 cell differentiation. Indeed, silencing the expression of SDF-1
      inhibits ATRA-induced granulocyte differentiation significantly. Taken together,
      these results indicate that SDF-1alpha is involved in granulocyte differentiation
      in response to ATRA, mediated by the activation of the transcription factor
      C/EBPbeta.

PMID- 29350864
TI  - Putting the brakes on leukocyte chemotaxis: an interview with Dr. Ramesh K.
      Ganju.

PMID- 29350865
TI  - Interview with Dr. Heikki Rauvala regarding Pivotal Advance: Analysis of
      proinflammatory activity of highly purified eukaryotic recombinant HMGB1
      (amphoterin).

PMID- 29350867
TI  - Interview with Dr. Maurizio C. Capogrossi regarding Pivotal Advance: High
      mobility group box 1 protein-a cytokine with a role in cardiac repair.

PMID- 29350869
TI  - Interview with Dr. Lee-Ann Allen regarding Pivotal Advance: Francisella
      tularensis LVS evades killing by human neutrophils via inhibition of the
      respiratory burst and phagosome escape.

PMID- 29350868
TI  - Errata.

PMID- 29350871
TI  - Interview with Dr. Francisco Sanchez-Madrid regarding Pivotal Advance: CD69
      targeting differentially affects the course of collagen-induced arthritis.

PMID- 29350872
TI  - Errata.

PMID- 29350873
TI  - Test Procedures to Assess Somatosensory Abnormalities in Individuals with
      Peripheral Joint Pain: A Systematic Review of Psychometric Properties.
AB  - BACKGROUND: Test procedures that were developed to assess somatosensory
      abnormalities should possess optimal psychometric properties (PMPs) to be used in
      clinical practice. The aim of this systematic review was to evaluate the
      literature to assess the level of evidence for PMPs of test procedures
      investigated in individuals with peripheral joint pain (PJP). METHODS: A
      comprehensive electronic literature search was conducted in 7 databases from
      inception to March 2016. The Quality Appraisal for Reliability Studies (QAREL)
      checklist and the Consensus-based Standards for the Selection of Health Status
      Measurement Instruments (COSMIN) tool were used to assess risk for bias of the
      included studies. Level of evidence was evaluated based on the methodological
      quality and the quality of the measurement properties. RESULTS: Forty-one studies
      related to PJP were included. The majority of included studies were considered to
      be of insufficient methodological quality, and the level of evidence for PMPs
      varied across different test procedures. The level of evidence for PMPs varied
      across different test procedures in different types of PJP. Hand-held pressure
      algometry is the only test procedure that showed moderate positive evidence of
      intrarater reliability, agreement, and responsiveness, simultaneously, when it
      was investigated in patients with chronic knee osteoarthritis. CONCLUSIONS: This
      systematic review identified that the level of evidence for PMPs varied across
      different testing procedures to assess somatosensory abnormalities for different
      PJP populations. Further research with standardized protocols is recommended to
      further investigate the predictive ability and responsiveness of reported test
      procedures in order to warrant their extended utility in clinical practice.

PMID- 29350875
TI  - Highly dynamic wintering strategies in migratory geese: Coping with environmental
      change.
AB  - When and where to move is a fundamental decision to migratory birds, and the
      fitness-related costs and benefits of migratory choices make them subject to
      strong selective forces. Site use and migration routes are outcomes of
      opportunities in the surrounding landscape, and the optimal migration strategy
      may be conservative or explorative depending on the variability in the
      environment occupied by the species. This study applies 25 years of resighting
      data to examine development in winter migration strategy of pink-footed geese
      divided among Denmark, the Netherlands and Belgium, and analyse potential drivers
      of strategy change as well as individuals' likelihood to break with migratory
      tradition. Contrary with the general notion that geese are highly traditional in
      their winter site use, our results reveal that winter migration strategy is
      highly dynamic in this species, with an average annual probability of changing
      strategy of 54%. Strategy was not related to hunting pressure or winter
      temperature, but could be partly explained by a tracking of food resources in a
      landscape of rapid land use changes. The probability of individuals changing
      strategy from year to year varied considerably between birds, and was partly
      related to sex and age, with young males being the most likely to change. The
      annual probability of changing wintering strategy increased substantially from
      ~40% to ~60% during the study period, indicating an increasingly explorative
      behaviour. Our findings demonstrate that individual winter strategies are very
      flexible and able to change over time, suggesting that phenotypic plasticity and
      cultural transmission are important drivers of strategy choice in this species.
      Growing benefits from exploratory behaviours, including the ability to track
      rapid land use changes, may ultimately result in increased resilience to global
      change.

PMID- 29350876
TI  - Mechanism of Mer receptor tyrosine kinase inhibition of glomerular endothelial
      cell inflammation.
AB  - Endotoxin induces a variety of proinflammatory mediators and plays a crucial role
      in kidney inflammation. The receptor tyrosine kinase, Mer, diminishes renal
      inflammation by attenuating inflammatory responses. We previously reported that
      Mer is predominantly expressed on glomerular endothelial cells (GECs) and that
      Mer deficiency is associated with increased renal inflammation when mice are
      challenged with nephrotoxic serum. We consequently hypothesized that Mer
      signaling down-regulates LPS-driven inflammatory responses in GECs. To test this
      hypothesis, primary GECs were isolated from the kidneys of Mer-KO and wild-type
      (WT) control mice. LPS treatment induced Akt and STAT3 activation along with Bcl
      xl up-regulation in WT GECs; these responses were all increased in Mer-deficient
      GECs. In addition, STAT1 and ERK1/2 up-regulation and activation were observed in
      Mer-KO GECs exposed to LPS. In contrast, expression of the inhibitory signaling
      molecule, suppressor of cytokine signaling-3 (SOCS-3), was much higher in LPS
      stimulated WT than Mer-deficient GECs. Deficiency of Mer was also associated with
      significantly increased NF-kappaB expression and activation. These observations
      indicate that Mer functions as an intrinsic feedback inhibitor of inflammatory
      mediator-driven immune responses in GECs during kidney injury and suggest a new
      therapeutic strategy for glomerular diseases.

PMID- 29350878
TI  - Perfusion computed tomography in posterior circulation stroke: predictors and
      prognostic implications of focal hypoperfusion.
AB  - BACKGROUND AND PURPOSE: The aim was to determine the predictors of focal
      hypoperfusion on computed tomography (CT) perfusion (CTP) in patients with acute
      posterior circulation stroke and its association with long-term outcome. METHODS:
      Patients with posterior circulation stroke were selected from the Acute Stroke
      Registry and Analysis of Lausanne (ASTRAL) who underwent CTP within 24 h of
      stroke onset as part of the stroke imaging protocol. Hypoperfusion was defined as
      an area of visually well demarcated mean transit time prolongation corresponding
      to an arterial territory on standard reconstruction CTP imaging maps. Areas of
      hypoperfusion were assessed with the posterior circulation Acute Stroke Prognosis
      Early CT Score. Clinical and imaging associations with focal hypoperfusion were
      identified using multiple imputation analyses, and the adjusted functional
      outcome measured by the modified Rankin Scale at 3 and 12 months was determined.
      RESULTS: Of the 3595 consecutive patients from the ASTRAL registry between 2003
      and 2014, 1070 (29.7%) had a posterior circulation stroke and 436 of these
      (40.7%) patients had a good quality baseline CTP. 23.1% had early ischaemic
      changes and 37.4% had focal hypoperfusion. In multiple imputation analysis,
      visual field deficits, reduced level of consciousness, cardiac and multiple
      stroke mechanisms, significant vessel pathology and ischaemic changes visible on
      plain CT were associated with focal hypoperfusion. Focal hypoperfusion was
      independently associated with outcome at 12 months (odds ratio 2.04, 95%
      confidence interval 1.22-3.42, P < 0.01). CONCLUSIONS: In posterior circulation
      stroke patients undergoing acute CTP, multiple clinical, aetiological and
      radiological variables were associated with focal hypoperfusion. Patients with
      focal hypoperfusion had a worse 12-month outcome.

PMID- 29350877
TI  - Effects of human rhinovirus on epithelial barrier integrity and function in
      children with asthma.
AB  - BACKGROUND: Bronchial epithelial tight junctions (TJ) have been extensively
      assessed in healthy airway epithelium. However, no studies have yet assessed the
      effect of human rhinovirus (HRV) infection on the expression and resultant
      barrier function in epithelial tight junctions (TJ) in childhood asthma.
      OBJECTIVES: To investigate the impact of HRV infection on airway epithelial TJ
      expression and barrier function in airway epithelial cells (AECs) of children
      with and without asthma. Furthermore, to test the hypothesis that barrier
      integrity and function is compromised to a greater extent by HRV in AECs from
      asthmatic children. METHODS: Primary AECs were obtained from children with and
      without asthma, differentiated into air-liquid interface (ALI) cultures and
      infected with rhinovirus. Expression of claudin-1, occludin and zonula occluden-1
      (ZO-1) was assessed via qPCR, immunocytochemistry (ICC), in-cell western (ICW)
      and confocal microscopy. Barrier function was assessed by transepithelial
      electrical resistance (TER; RT ) and permeability to fluorescent dextran.
      RESULTS: Basal TJ gene expression of claudin-1 and occludin was significantly
      upregulated in asthmatic children compared to non-asthmatics; however, no
      difference was seen with ZO-1. Interestingly, claudin-1, occludin and ZO-1
      protein expression was significantly reduced in AEC of asthmatic children
      compared to non-asthmatic controls suggesting possible post-transcriptional
      inherent differences. HRV infection resulted in a transient dissociation of TJ
      and airway barrier integrity in non-asthmatic children. Although similar
      dissociation of TJ was observed in asthmatic children, a significant and
      sustained reduction in TJ expression concurrent with both a significant decrease
      in TER and an increase in permeability in asthmatic children was observed.
      CONCLUSION: This study demonstrates novel intrinsic differences in TJ gene and
      protein expression between AEC of children with and without asthma. Furthermore,
      it correlates directly the relationship between HRV infection and the resultant
      dissociation of epithelial TJ that causes a continued altered barrier function in
      children with asthma.

PMID- 29350874
TI  - Diversification of human NK cells: Lessons from deep profiling.
AB  - NK cells are innate lymphocytes with important roles in immunoregulation,
      immunosurveillance, and cytokine production. Originally defined on the functional
      basis of their "natural" ability to lyse tumor targets and thought to be a
      relatively homogeneous group of lymphocytes, NK cells possess a remarkable degree
      of phenotypic and functional diversity due to the combinatorial expression of an
      array of activating and inhibitory receptors. Diversification of NK cells is
      multifaceted: mechanisms of NK cell education that promote self-tolerance result
      in a heterogeneous repertoire that further diversifies upon encounters with viral
      pathogens. Here, we review the genetic, developmental, and environmental sources
      of NK cell diversity with a particular focus on deep profiling and single-cell
      technologies that will enable a more thorough and accurate dissection of this
      intricate and poorly understood lymphocyte lineage.

PMID- 29350879
TI  - Genetic and Chemical Diversity in Perovskia abrotanoides Kar. (Lamiaceae)
      Populations Based on ISSRs Markers and Essential Oils Profile.
AB  - Genetic and the essential oil composition variability among twelve Perovskia
      abrotanoides populations (PAbPs) growing wild in Iran were assessed by ISSR
      markers, GC-FID and GC/MS, respectively. Nine selected ISSR primers produced 119
      discernible bands, of them 96 (80.7%) being polymorphic. Genetic similarity
      values among populations ranged between 0.07 and 0.79 which indicated a high
      level of genetic variation. Polymorphic information content, resolving power and
      marker index generated by ISSR primers were, 0.31, 6.14, and 3.32, respectively.
      UPGMA grouped PAbPs into four main clusters. Altogether, 38 chemical compounds
      were identified in the oils, and a relatively high variation in their contents
      was found. Camphor (11.9 - 27.5%), 1,8-cineole (11.3 - 21.3%), alpha-bisabolol
      (0.0 - 13.1%), alpha-pinene (5.9 - 10.8%), and delta-3-carene (0.1 - 10.5%) were
      the major compounds. Oxygenated monoterpenes (32.1 - 35.8%) and monoterpene
      hydrocarbons (25.7 - 30.4%) were the main groups of compounds in the oils
      studied. Cluster analysis and principal-component analysis were used to
      characterize the samples according to oil components. Four main chemotypes were
      found to be Chemotype I (camphor/1,8-cineol), Chemotype II (1,8-cineole/camphor),
      Chemotype III (camphor/1,8-cineol/alpha-bisabolol), and Chemotype IV
      (camphor/delta-3-carene/alpha-bisabolol). The information, provided here on P.
      abrotanoides populations, will be useful to introduce this plant into
      agricultural systems.

PMID- 29350880
TI  - Temporal and Spatial Quantification of Pain- Related Small Fiber Functionality
      Assessed Using Laser Speckle Contrast Analysis.
AB  - BACKGROUND: This study aimed to establish a practical method for assessing pain
      symptomatology and develop criteria for quantifying small fiber functions using
      laser speckle contrast analysis (LASCA). METHODS: Axon flare responses, which
      reflect small fiber functions, were induced either by histamine or capsaicin
      applied to the volar surface of the skin of the left forearm. To inhibit small
      fiber function, local anesthetic cream was applied to the skin of right forearm.
      The effects on pain symptomatology (severity/timing) and axon flare responses
      (temporal/spatial characteristics) were measured using LASCA. To highlight the
      clinical relevance, this method was applied to 3 different types of patients with
      small fiber dysfunction. RESULTS: Forty-four forearms of 22 healthy volunteers
      were tested. Eutectic mixture local anesthetic cream reduced the severity and
      duration of pain, abolishing or prolonging the latency to reach 3-fold higher
      levels of basal skin microcirculation levels, and decreasing the area and
      intensity of flare responses. There were positive correlations between pain
      symptomatology and flare response characteristics in the control forearm. Similar
      results were confirmed in neuropathic pain patients. CONCLUSIONS: Pain-related
      small fiber functions and symptomatology (two-in-one method) can be assessed via
      histamine- or capsaicin-evoked axon flare responses in as little as 15 minutes.
      The reduction of small fiber functions are characterized by decrease in flare
      size/intensity at 5 minutes after stimulation and prolongation/abolishment of the
      latency to reach 3-fold higher levels of baseline skin microcirculation. LASCA
      may be applied in the clinic to aid early diagnosis, monitor disease progression,
      and objectively assess treatment efficacy in patients with neuropathic pain.

PMID- 29350881
TI  - Interferon-induced protein 35 inhibits endothelial cell proliferation, migration
      and re-endothelialization of injured arteries by inhibiting the nuclear factor
      kappa B pathway.
AB  - AIM: Endothelial recovery, or re-endothelialization, plays an important role in
      intimal hyperplasia and atherosclerosis after endothelial injury. Studying the
      mechanisms of re-endothelialization and strategies to promote efficient
      endothelial recovery are still needed. Interferon-induced protein 35 (IFI35) is
      an IFN-gamma-induced protein that plays important roles in the antivirus-related
      immune-inflammatory response. In this study, we tested whether overexpression
      IFI35 affects the proliferation and migration of endothelial cells (ECs) and re
      endothelialization. METHODS: Wire injury of the carotid artery was induced in
      C57BL/6 mice, which was followed by IFI35 or null adenovirus transduction. Evans
      blue staining and HE staining were performed to evaluate the re
      endothelialization rate and neointima formation. In vitro studies, primary human
      umbilical vein endothelial cells (HUVECs) were transfected with Ad-IFI35 or siRNA
      IFI35 to evaluate its potential roles in cell proliferation and migration.
      Furthermore, the potential mechanism relating inhibition of NF-kappaB/p65 pathway
      was elaborated by luciferase assay and IFI35 domain deletion assay. RESULTS: In
      IFI35 adenovirus-transduced mice, the re-endothelialization rates at days 3, 7
      were significantly reduced compared to those in null adenovirus-transduced mice
      (5% and 35%, vs 20% and 50%, respectively). Meanwhile, subsequent neointimal
      hyperplasia was obviously increased in IFI35 adenovirus-transduced mice. In vitro
      studies further indicated that IFI35 inhibits both EC proliferation and migration
      by inhibiting the NF-kappaB/p65 pathway. Subsequent studies demonstrated that
      IFI35 functionally interacted with Nmi through its NID1 domain and that knock
      down of Nmi significantly mitigated the inhibitory effect of IFI35 on EC
      proliferation and migration. CONCLUSION: Our study revealed a novel mechanism
      through which IFI35 affects the proliferation and migration of ECs as well as
      neointima formation, specifically through inhibition of the NF-kappaB/p65
      pathway. Thus, IFI35 is a promising target for the prevention and treatment of
      post-injury vascular intimal hyperplasia.

PMID- 29350882
TI  - Cardiac function on 3-D speckle tracking imaging and cytokines in Kawasaki
      disease.
AB  - BACKGROUND: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) tends to
      rise in acute phase Kawasaki disease (KD), but the cause of NT-proBNP elevation
      has not been clarified. In a previous study, cardiac function evaluated on 2-D
      echocardiography (2D-E) such as ejection fraction was normal, but this does not
      reflect subtle changes in cardiac dysfunction, and hence the association between
      cardiac function and NT-proBNP elevation is still controversial. The aim of this
      study was therefore to elucidate the influence of cardiac function on NT-proBNP
      elevation, by evaluating cardiac function via strain on 3-D speckle tracking
      imaging (3D-STI), in acute and subacute KD patients. Given that cytokines are
      also thought to induce NT-proBNP in acute phase KD, serum cytokines and cytokine
      receptors were measured at the same time. METHODS: Laboratory data and
      echocardiography in 52 KD patients in the acute and subacute phases were
      reviewed. RESULTS: Median NT-proBNP was significantly elevated in the acute phase
      compared with the subacute phase (356.5 pg/mL; IQR, 145-904 pg/mL vs 103.5 pg/mL;
      IQR, 59-150 pg/mL, P < 0.01). All cytokines were also significantly elevated in
      the acute phase compared with the subacute phase. Tumor necrosis factor (TNF)
      alpha, soluble TNF receptor (sTNFR)1, and sTNFR2 concentration were all
      significantly higher in the acute phase. Indices of cardiac function were not
      significant different between phases. NT-proBNP in the acute and subacute phases
      correlated with sTNFR1 (r = 0.63/0.43, P < 0.01), sTNFR2 (r = 0.50/0.31, P <
      0.05), and interleukin-6 (r = 0.58/0.43, P < 0.01). NT-proBNP did not correlate
      with global longitudinal strain (GLS) on 3D-STI. CONCLUSION: Although no
      correlation was seen between NT-proBNP and GLS on 3D-STI, correlations between NT
      proBNP and cytokines were clear. NT-proBNP might be a marker of inflammation in
      KD, but is not a marker of cardiac function.

PMID- 29350883
TI  - Peri-implant conditions and levels of advanced glycation end products among
      patients with different glycemic control.
AB  - BACKGROUND: A close relationship between poor glycemic control and peri-implant
      break down has been demonstrated. It is hypothesized that levels of advanced
      glycation end products (AGEs) in peri-implant sulcular fluid (PISF) are higher
      with increased glycemic levels in type 2 diabetes mellitus patients. PURPOSE: In
      the present study, we examined the clinical and radiographic peri-implant
      parameters and levels of AGEs among different glycemic levels in diabetic
      patients and assessed whether the levels of AGEs correlate with clinical peri
      implant parameters. MATERIALS AND METHODS: Ninety-three patients who participated
      in this study were divided into four groups; Group-1: HbA1c 6.1%-8%; Group-2:
      HbA1c 8.1%-10%; Group-3: HbA1c > 10%; Group-4: non-diabetic individuals with
      HbA1c < 6%. Peri-implant plaque index (PI), bleeding on probing (BOP), probing
      depth (PD) and crestal bone loss (CBL) were recorded. Levels of AGEs in PISF were
      quantified using enzyme-linked immunosorbent assay. Between-group comparison of
      means was verified with Kruskal-Wallis test and Pearson correlation coefficient
      for correlations of AGE levels with peri-implant parameters. RESULTS: Peri
      implant PI, BOP, PD, and CBL were significantly higher in group-1, -2, and -3 as
      compared to non-diabetic patients (P < .05). These parameters were significantly
      higher in group-2 and group-3 versus group-1 (P < .01). Mean PI, BOP, PD, and CBL
      were comparable between group-2 and group-3 patients (P > .05). Mean levels of
      AGEs in PISF were significantly higher in relation to higher levels of HbA1c
      levels. Significant positive correlations were found between AGEs and PD (P =
      .0221) and CBL (P = .0425); and significant negative correlation was found for PI
      (P = .0376) in patients with HbA1c levels >10%, respectively. CONCLUSIONS:
      Clinical and radiographic peri-implant parameters were poor and levels of AGEs
      were significantly high in patients with high glycemic levels. These findings
      suggest that AGEs may be considered as potential marker of inflammation in
      diabetic individuals with peri-implantitis.

PMID- 29350884
TI  - Management of Medically Refractory Central Poststroke Pain Using High-Frequency
      Spinal Cord Stimulation at 10 kHz.

PMID- 29350885
TI  - Unexpected impact of esterification on the antioxidant activity and
      (photo)stability of a eumelanin from 5,6-dihydroxyindole-2-carboxylic acid.
AB  - To inquire into the role of the carboxyl group as determinant of the properties
      of 5,6-dihydroxyindole melanins, melanins from aerial oxidation of 5,6
      dihydroxyindole-2-carboxylic acid (DHICA) and its DHICA methyl ester (MeDHICA)
      were comparatively tested for their antioxidant activity. MALDI MS spectrometry
      analysis of MeDHICA melanin provided evidence for a collection of intact
      oligomers. EPR analysis showed g-values almost identical and signal amplitudes
      (DeltaB) comparable to those of DHICA melanin, but spin density was one order of
      magnitude higher, with a different response to pH changes. Antioxidant assays
      were performed, and a model of lipid peroxidation was used to compare the
      protective effects of the melanins. In all cases, MeDHICA melanin performed
      better than DHICA melanin. This capacity was substantially maintained following
      exposure to air in aqueous buffer over 1 week or to solar simulator over 3 hr.
      Different from DHICA melanin, MeDHICA melanin was proved to be fairly soluble in
      different water-miscible organic solvents, suggesting its use in dermocosmetic
      applications.

PMID- 29350886
TI  - The cell biology and molecular genetics of Mullerian duct development.
AB  - The Mullerian ducts are part of the embryonic urogenital system. They give rise
      to mature structures that serve a critical function in the transport and
      development of the oocyte and/or embryo. In most vertebrates, both sexes
      initially develop Mullerian ducts during embryogenesis, but they regress in males
      under the influence of testis-derived Anti-Mullerian Hormone (AMH). A number of
      regulatory factors have been shown to be essential for proper duct development,
      including Bmp and Wnt signaling molecules, together with homeodomain
      transcription factors such as PAX2 and LIM1. Later in development, the fate of
      the ducts diverges between males and females and is regulated by AMH and Wnt
      signaling molecules (duct regression in males) and Hox genes (duct patterning in
      females). Most of the genes and molecular pathways known to be involved in
      Mullerian duct development have been elucidated through animal models, namely,
      the mouse and chicken. In addition, genetic analysis of humans with reproductive
      tract disorders has further defined molecular mechanisms of duct formation and
      differentiation. However, despite our current understanding of Mullerian duct
      development, some questions remain to be answered at the molecular genetic level.
      This article is categorized under: Early Embryonic Development > Development to
      the Basic Body Plan.

PMID- 29350887
TI  - Species-specific clinical characteristics of human coronavirus infection among
      otherwise healthy adolescents and adults.
AB  - Human coronavirus (HCoV) is a known cause of influenza-like illness (ILI). In a
      multisite, observational, longitudinal study of ILI among otherwise healthy
      adolescents and adults, 12% of subjects were PCR-positive for HCoV. The
      distribution of species was as follows: HCoV-OC43 (34%), HCoV-229E (28%), HCoV
      NL63 (22%), and HCoV-HKU1 (16%). We did not observe species-specific differences
      in the clinical characteristics of HCoV infection, with the exception of HCoV
      HKU1, for which the severity of gastrointestinal symptoms trended higher on the
      fourth day of illness.

PMID- 29350888
TI  - Identification of p90 Ribosomal S6 Kinase 2 as a Novel Host Protein in HBx
      Augmenting HBV Replication by iTRAQ-Based Quantitative Comparative Proteomics.
AB  - PURPOSE: The aim of this study was to screen for novel host proteins that play a
      role in HBx augmenting Hepatitis B virus (HBV) replication. EXPERIMENTAL DESIGN:
      Three HepG2 cell lines stably harboring different functional domains of HBx (HBx,
      HBx-Cm6, and HBx-Cm16) were cultured. ITRAQ technology integrated with LC-MS/MS
      analysis was applied to identify the proteome differences among these three cell
      lines. RESULTS: In brief, a total of 70 different proteins were identified among
      HepG2-HBx, HepG2-HBx-Cm6, and HepG2-HBx-Cm16 by double repetition. Several
      differentially expressed proteins, including p90 ribosomal S6 kinase 2 (RSK2),
      were further validated. RSK2 was expressed at higher levels in HepG2-HBx and
      HepG2-HBx-Cm6 compared with HepG2-HBx-Cm16. Furthermore, levels of HBV
      replication intermediates were decreased after silencing RSK2 in HepG2.2.15. An
      HBx-minus HBV mutant genome led to decreased levels of HBV replication
      intermediates and these decreases were restored to levels similar to wild-type
      HBV by transient ectopic expression of HBx. After silencing RSK2 expression, the
      levels of HBV replication intermediates synthesized from the HBx-minus HBV mutant
      genome were not restored to levels that were observed with wild-type HBV by
      transient HBx expression. CONCLUSION AND CLINICAL RELEVANCE: Based on iTRAQ
      quantitative comparative proteomics, RSK2 was identified as a novel host protein
      that plays a role in HBx augmenting HBV replication.

PMID- 29350889
TI  - Predictors of overweight and obesity among adults aged 50 years and above:
      Serbian national health survey.
AB  - Background/Aim: Obesity is a complex and multifactorial condition related to
      morbidity, mortality, poor quality of life and many other problems. The aim of
      the study was to determine the prevalence of overweight and obesity and factors
      associated with them (demographic, socioeconomic factors and lifestyle) in adults
      aged 50 years and above in Serbia. Methods: This cross-sectional study,
      representative for the population in Serbia, was carried out in one-year period,
      including 6,932 people aged 50 and over. Individuals were interviewed and
      anthropometrically examined. The association between overweight and obesity with
      demographic, socioeconomic and behavioral factors was analyzed using multivariate
      logistic regression. Results: Age, level of education and smoking were
      significantly associated with overweight and obesity, regardless of gender.
      Marital status was significantly associated with obesity, regardless of gender
      and with overweight only in women. Breakfast consumption habit was significantly
      associated with obesity only in men. There was no significant association of
      overweight and obesity with the type of settlement, alcohol consumption and
      physical activity, regardless of gender. Conclusion: The results of our study
      indicate the need for more intensive implementation of measures affecting the
      factors which contribute to overweight and obesity. Emphasis should be put on the
      population-based policies and programs that support environmental changes.

PMID- 29350890
TI  - Relationship between outpatient antibiotic use and the prevalence of bacterial
      infections in Montenegro.
AB  - Background/Aim: The overuse of antibiotics unnecessarily exposes patients to risk
      of side effects, encourages reconsultation for similar problems and enhances
      antimicrobial resistance. The use of antibiotics in the year 2011 in Montenegro
      was high (39.05 Defined Daily Dose - DDD/1,000 inhabitants/day), but it was not
      considered in relation to the frequency of bacterial diseases. The aim of our
      study was to determine the degree of conformance between the amount of outpatient
      antibiotic consumption and the reported prevalence of outpatient bacterial
      infections in the Republic of Montenegro. Methods: Data on the use of
      antibacterial drugs was obtained from the Agency for Medicines and Medical
      Devices of Montenegro for the year 2012. The amount of antibiotics was calculated
      using the Anatomic Therapeutic Chemical (ATC) DDD methodology. Data on the
      prevalence of outpatient infective disease was obtained from the Health
      Statistical Yearbook 2012 of Montenegro and it was expressed per 1,000
      inhabitants. Results: A total of 30.34 DDD/1,000 inhabitants/day of antibiotics
      in outpatients were prescribed in Montenegro in 2012, with penicillins being most
      frequently prescribed. Amoxicillin and amoxicillin with clavulanic acid were the
      most frequently used antibiotics. The prevalence of outpatient bacterial
      infections was 6,745 cases or 10.87/1,000. The most frequent infections were
      respiratory tract infections. Less than 50% of the prescribed amount of
      antibiotics were prescribed in accordance with national guidelines on treatment
      of bacterial infections. Conclusion: Use of antibiotics in Montenegro in 2012 was
      more than double than necessary according to prevalence of bacterial infections
      and average duration of treatment. The structure of antibiotics was not in full
      compliance with the national good practice guidelines, but it was in accordance
      with data on bacterial antibiotic resistance in outpatient practice. It is
      necessary to initiate measures to rationalize the use of antibiotics both in
      terms of quantity and in terms of the structure of the most used antibiotics.

PMID- 29350891
TI  - First experiences with the Fitmore(r) hip stem: Early results of the 16-month
      monitoring.
AB  - Background/Aim: Fitmore(r) hip stem belongs to the group of short stem prostheses
      with the metaphysar stabilization, with its shape and form that protects the bone
      mass in the greater trochanter region and the distal part of the femur. The aim
      of this paper was to present the early postoperative results in patients with
      implanted Fitmore(r) hip stem and point out some of the advantages. Methods: A
      series of 10 patients with implanted Fitmore(r) hip stem, was included in this
      study. The average age of the patients was 54.5 (48-65) years. There were 5 women
      and 5 men. The total monitoring time was 16 months. To rate the condition of the
      hip joint we used The Western Ontario and Mc Master Universities Arthritis Index
      (WOMAC) score. We also monitored the degree of hip pain, hip flexion, heterotopic
      ossification and indentation in the stem of the prosthesis. Results: After 12
      months of monitoring 9 (90%) of the patients had no pain in the thigh region, and
      only 1 (10%) experienced mild pain. The hip flexion rose from the average 89
      degrees  to postoperative 114 degrees . WOMAC score rose as well, from 49 to 94
      average points. Indentation in the stem was registered 3 months after the
      operation in 2 (20%) of the patients - in one of the patients the indentation was
      3 mm and in the other patient 5 mm. After the 16-month monitoring, the results
      were excellent. The monitoring period was short though it should be continued and
      the results should be presented after 5 and then after 10 years. Conclusion:
      Early results of the implantation Fitmore stem showed good bone ingrowth with
      excellent functional result.

PMID- 29350892
TI  - Risk factors for cardiovascular disease in children on chronic hemodialysis -
      Uremia related (non-traditional) risk factors, part II.

PMID- 29350893
TI  - Silent sinus syndrome: One more reason for an ophthalmologist to have a
      rhinologist as a good friend.

PMID- 29350894
TI  - An enigma of eosinophilic esophagitis.
AB  - Introduction: Eosinophilic esophagitis is a chronic immunogenic-antigen mediated
      disease of the esophagus, characterized by symptoms related to esophagus
      dysfunction, histologically defined by over 15 eosinophil counts seen in high
      power microscopic field, without gastroesophageal reflux disease. In adults, the
      most common clinical manifestations are dysphagia, reflux, chest pain,
      regurgitation and bolus impaction. Case report: We presented the case of a female
      patient, hospitalized for a serious form of pancreatitis with complications,
      which required artificial ventilation and enteral feeding, after the initial
      esophagoscopy verified reflux esophagitis. Further treatment cured the primary
      illness, and peroral feeding was reintroduced. However, dysphagia with
      regurgitation occurred, and endoscopic and radiological tests verified esophagus
      stenosis, which histopathologically corresponded to erosive esophagitis. Two
      months of treatment by a double dosage of proton pump inhibitors led to no
      regression of disorders, and the repeated biopsies from the stenotic segments
      resulted in over 30 eosinophil counts in the high-power microscopic field, which
      histologically corresponds to eosinophilic esophagitis. Subsequent therapy
      included fluticasone 880 MUg/day orally for a period of eight weeks, which led to
      complete regression of disorders, and endoscopic and histopathologic remission.
      Conclusion: In case of irresponsiveness to the conventional therapy by proton
      pump inhibitors, repeated esophagoscopy and histopathological analyses of
      esophagus mucosa biopsy can point to the diagnosis of eosinophilic esophagitis,
      and a good therapeutic response to topical corticosteroids can be regarded as the
      clinical confirmation of the diagnosis.

PMID- 29350895
TI  - Pastoral care and religious support as a part of treatment of religious patient
      with the severe form of osteoarthritis.
AB  - Introduction: Religious needs of patients are consistently being neglected in the
      clinical medicine. Pastoral care is a religious support which a religious patient
      receives from priests, chaplains, imams, rabbis or other religious authorities.
      Religious support, in terms of clinical medicine, is a spiritual support which
      religious patients obtain from religious and trained medical workers. The aim of
      this report was to present the effects of pastoral care and religious support in
      hospital treatment of a 73-year-old patient with the severe form of
      osteoarthritis. Case report: The 73- year-old, highly religious patient with
      severe form of osteoarthritis was admitted at the Clinic for Physical Medicine
      and Rehabilitation, Military Medical Academy in Belgrade, due to heterogeneous
      problems in the activities of daily living. The patient walked with difficulty
      using a stick, suffered pain, and was anxious and depressive. In order to
      objectively demonstrate effects of both pastoral care and religious support in
      this patient we performed multiple treatment with reversal design, in which the
      basic treatment consisting of hospital care, pharmacotherapy and physical therapy
      (the treatment A) was alternatively changed with the treatment that included
      combination of the basic treatment and religious support provided by religious
      physiatrist and physiotherapist (the treatment B) or combination of the basic
      treatment and pastoral care provided by military priest (the treatment C). The
      treatment A was applied three times and lasted two weeks, every time. Treatments
      B and C were applied once and lasted three weeks, each. The order of the
      treatments was: A->B->A->C->A. During the whole treatment period the patient's
      condition was assessed by several measuring scale: the level of depression by The
      Hamilton Rang Scale for Depression and The Zung Self Rating Depression Scale; the
      level of anxiety by The Zung Self Rating Anxiety Scale; the functional capability
      of patient by The Barthel Index and The Functional Independent Measure. Measuring
      was carried out on a daily basis. In statistical analysis two nonparametric
      statistic were used: the percentage of non-overlapping data (PND) and the
      percentage of data points exceeding the median (PEM). PND and PEM values below
      0.7 reflect questionable effectiveness of the treatment. The values between 0.7
      and 0.9 reflect moderate effects. The values above 0.9 are considered as a highly
      effective treatment. The anxiety of the patient was moderately to significantly
      reduced after introducing religious support (treatment B: mean and mean deviation
      = 50.1 +/- 10.89; variability = 4.598653; mean shift = 0.219626; PND = 0.6; PEM =
      0.9) and pastoral care (treatment C: mean and mean deviation = 53.5 +/- 5.90;
      variability = 9.062591; mean shift = 0.207407; PND = 0.9; PEM = 0.9). The
      patient's depression was reduced after introducing pastoral care (treatment C:
      mean and mean deviation = 51.3 +/- 4.66; variability = 10.99005; mean shift =
      0.08881; PND = 0; PEM = 0.9). On the contrary, the patient's functional
      capability was not significantly improved. Conclusion: In the highly religious
      patient with severe osteoarthritis pastoral care and religious support, applied
      along with the standard medical treatment of this condition, produced some
      beneficial effects on anxiety and depressive mood, but with no significant effect
      on patient's functional capability.

PMID- 29350896
TI  - Transverse colon volvulus in neurologicaly imparied patient as an emergency
      surgical condition: A case report.
AB  - Introduction: Transverse colon volvulus is an uncommon cause of bowel obstruction
      in general. Predisposing factors are mental retardation, dysmotility disorders,
      chronic constipation and congenital megacolon. Case report: We presented
      transverse colon volvulus in a 16-year-old boy with cerebral palsy. Chronic
      constipation in neurologicaly impaired patient was a risk factor predisposing to
      volvulus. The patient was admitted to the hospital with enormous abdominal
      distension and acute respiratory insufficiency. A boy was emergently taken to the
      operating room for exploratory laparotomy. During the surgery, a 360o clockwise
      volvulus of the transverse colon was found. After reduction of volvulus, an
      enormous transverse colon was resected and colostomy was formed. In the
      postoperative period, despite the good functioning of stoma and intraabdominal
      normotension, numerous and long lasting respiratory problems developed. The
      patient was discharged from our institution after 8 months. Conclusion: Though
      very rare in pediatric group, the possibility of a transverse colon volvulus must
      be considered in the differential diagnosis of acute large bowel obstruction.

PMID- 29350898
TI  - Identification of Individual Bacterial Cells through the Intermolecular
      Interactions with Peptide-Functionalized Solid-State Pores.
AB  - Bioinspired pore sensing for selective detection of flagellated bacteria was
      investigated. The Au micropore wall surface was modified with a synthetic peptide
      designed from toll-like receptor 5 (TLR5) to mimic the pathogen-recognition
      capability. We found that intermolecular interactions between the TLR5-derived
      recognition peptides and flagella induce ligand-specific perturbations in the
      translocation dynamics of Escherichia coli, which facilitated the discrimination
      between the wild-type and flagellin-deletion mutant (DeltafliC) by the resistive
      pulse patterns thereby demonstrating the sensing of bacteria at a single-cell
      level. These results provide a novel concept of utilizing weak intermolecular
      interactions as a recognition probes for single-cell microbial identification.

PMID- 29350897
TI  - Aortobifemoral reconstruction and renal transplantation in a patient with
      abdominal aortic aneurysm and occlusion of iliac arteries: A case report.
AB  - Introduction: Aortoiliac occlusive disease and abdominal aortic aneurysm in
      patients with renal insufficiency on hemodialysis can significantly influence the
      success of renal transplantation. In the recent past, advanced atherosclerosis
      was considered as contraindication for renal transplantation. Complicated
      creation of vascular anastomoses and progression of occlusive or aneurysmal
      disease were the main reasons. Case report: We presented a 52-year-old man with a
      5-year history of end-stage renal disease on haemodialysis. The patient was
      previously excluded from renal transplantation program because of severe
      aortoiliac atherosclerosis and abdominal aortic aneurysm. Resection of abdominal
      aortic aneurysm with occlusion of the iliac arteries and reconstruction with
      aortobifemoral synthetic grafts was performed and followed by cadaveric renal
      transplantation. Conclusion: Advanced atherosclerotic disease in aortoiliac
      segment requires elective vascular surgical reconstruction, as part of
      preparation for renal transplantation in patients with end-stage renal disease.

PMID- 29350899
TI  - Cyclam-Modified PEI for Combined VEGF siRNA Silencing and CXCR4 Inhibition To
      Treat Metastatic Breast Cancer.
AB  - Chemokine receptor CXCR4 plays an important role in cancer cell invasion and
      metastasis. Recent findings suggest that anti-VEGF therapies upregulate CXCR4
      expression, which contributes to resistance to antiangiogenic therapies. Here, we
      report the development of novel derivatives of polyethylenimine (PEI) that
      effectively inhibit CXCR4 while delivering anti-VEGF siRNA. PEI was alkylated
      with different amounts of a CXCR4-binding cyclam derivative to prepare PEI-C.
      Modification with the cyclam derivatives resulted in a considerable decrease in
      cytotoxicity when compared with unmodified PEI. All the PEI-C showed significant
      CXCR4 antagonism and the ability to inhibit cancer cell invasion. Polyplexes of
      PEI-C prepared with siVEGF showed effective silencing of the VEGF expression in
      vitro. In vivo testing in a syngeneic breast cancer model showed promising
      antitumor and antimetastatic activity of the PEI-C/siVEGF polyplexes. Our data
      demonstrate the feasibility of using PEI-C as a carrier for simultaneous VEGF
      silencing and CXCR4 inhibition for enhanced antiangiogenic cancer therapies.

PMID- 29350900
TI  - Fluorescent TPA@GQDs Probe for Sensitive Assay and Quantitative Imaging of
      Hydroxyl Radicals in Living Cells.
AB  - A fluorescent probe TPA@GQDs is fabricated by the conjugation of terephthalic
      acid (TPA) on the surface of graphene quantum dots (GQDs). The TPA@GQDs probe not
      only has favorable dispersibility but also exhibits excellent fluorescence
      stability over a wide pH range and high ionic strength and favorable
      antiphotobleaching ability. The great fluorescence enhancement of TPA@GQDs
      induced by the reaction between TPA and hydroxyl radicals makes the TPA@GQDs a
      powerful probe for the sensitive assay of hydroxyl radicals, giving rise to a low
      detection limit down to 12 nmol L-1. Meanwhile, the obtained fluorescent TPA@GQDs
      probe shows low cytotoxicity and favorable biocompatibility. Its potential in
      bioimaging is demonstrated by the quantitative fluorescent imaging of hydroxyl
      radicals in living HeLa cells under different circumstances, which enables the
      opportunities to study hydroxyl radicals dynamics in living cells.

PMID- 29350901
TI  - Adsorption and Diffusion of Lithium and Sodium on Defective Rhenium Disulfide: A
      First Principles Study.
AB  - Single-layer rhenium disulfide (ReS2) is a unique material with distinctive,
      anisotropic electronic, mechanical, and optical properties and has the potential
      to be used as an anode in alkali-metal-ion batteries. In this work, first
      principles calculations were performed to systematically evaluate the potential
      of monolayer pristine and defective ReS2 as anodes in lithium (Li)- and sodium
      (Na)-ion batteries. Our calculations suggest that there are several potential
      adsorption sites for Li and Na on pristine ReS2, owing to its low-symmetry
      structure. Additionally, the adsorption of Li and Na over pristine ReS2 is very
      strong with adsorption energies of -2.28 and -1.71 eV, respectively.
      Interestingly, the presence of point defects causes significantly stronger
      binding of the alkali-metal atoms with adsorption energies in the range -2.98 to 
      3.17 eV for Li and -2.66 to -2.92 eV for Na. Re single vacancy was found to be
      the strongest binding defect for Li adsorption, whereas S single vacancy was
      found to be the strongest for Na. The diffusion of these two alkali atoms over
      pristine ReS2 is anisotropic, with an energy barrier of 0.33 eV for Li and 0.16
      eV for Na. The energy barriers associated with escaping a double vacancy and
      single vacancy for Li atoms are significantly large at 0.60 eV for the double
      vacancy case and 0.51 eV for the single-vacancy case. Similarly, for Na, they are
      0.59 and 0.47 eV, respectively, which indicates slower migration and sluggish
      charging/discharging. However, the diffusion energy barrier over a Re single
      vacancy is found to be merely 0.42 eV for a Li atom and 0.28 eV for Na. Overall,
      S single and double vacancies can reduce the diffusion rate by 103-105 times for
      Li and Na ions, respectively. These results suggest that monolayer ReS2 with a Re
      single vacancy adsorbs Li and Na stronger than pristine ReS2, with negligible
      negotiation with the charging/discharging rate of the battery, and therefore they
      can be used as an anode in Li- and Na-ion batteries.

PMID- 29350902
TI  - Hierarchically Self-Assembled Supramolecular Host-Guest Delivery System for Drug
      Resistant Cancer Therapy.
AB  - In this report, a new star-like copolymer beta-CD- g-(PNIPAAm- b-POEGA) x,
      consisting of a beta-CD core, grafted with temperature-responsive poly( N
      isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol)
      acrylate) (POEGA) in a block copolymer of the arms, was used to deliver
      chemotherapeutics to drug resistant cancer cells and tumors. The first step of
      the self-assembly process involves the encapsulation of chemotherapeutics through
      host-guest inclusion complexation between the beta-cyclodextrin cavity and the
      anticancer drug. Next, the chain interaction of the PNIPAAm segment at elevated
      temperature drives the drug-loaded beta-CD- g-(PNIPAAm- b-POEGA) x/PTX inclusion
      complex to hierarchically self-assemble into nanosized supramolecular assemblies
      at 37  degrees C, whereas the presence of poly(ethylene glycol) (PEG) chains in
      the distal end of the star-like copolymer arms impart enhanced stability to the
      self-assembled structure. More interestingly, this supramolecular host-guest
      nanocomplex promoted the enhanced cellular uptake of chemotherapeutics in MDR-1
      up-regulated drug resistant cancer cells and exhibited high therapeutic efficacy
      for suppressing drug resistant tumor growth in an in vivo mouse model, due to the
      increased stability, improvement in aqueous solubility, enhanced cellular uptake,
      and partial membrane pump impairment by taking the advantage of PEGylation and
      supramolecular complex between this star-like copolymer and chemotherapeutics.
      This work signifies that temperature-sensitive PEGylated supramolecular
      nanocarriers with good biocompatibility are effective in combating MDR-1 mediated
      drug resistance in both in vitro and in vivo models, which is of significant
      importance for the advanced drug delivery platform designed to combat drug
      resistant cancer.

PMID- 29350903
TI  - Self-Assembly of Protein Crystals with Different Crystal Structures Using Tobacco
      Mosaic Virus Coat Protein as a Building Block.
AB  - In this work, a typical cylinder-shaped tobacco mosaic virus coat protein (TMVCP)
      is employed as an anisotropic building block to assemble into triclinic and
      hexagonal close-packed (HCP) protein crystals by introducing cysteine residues at
      the 1 and 3 sites and four histidine residues at the C-terminal, respectively.
      The engineered functional groups of cysteine and histidine in the TMVCP and the
      self-assembly conditions determine the thermodynamics and kinetics in the self
      assembly process for forming different crystal structures. The results show that
      the TMVCPs are thermodynamically driven to form triclinic crystals due to the
      formation of disulfide bonds between neighboring TMVCPs. On the other hand, the
      self-assembly of HCP crystals is kinetically directed by the strong metal
      histidine chelation. This work not only greatly expands TMVCP for fabricating
      promising nanomaterials but also represents an approach to adjusting the protein
      crystal structures by tuning the thermodynamics and kinetics during
      crystallization.

PMID- 29350904
TI  - Nanoplatform Assembled from a CD44-Targeted Prodrug and Smart Liposomes for Dual
      Targeting of Tumor Microenvironment and Cancer Cells.
AB  - The tumor microenvironment (TME) plays a critical role in tumor initiation,
      progression, invasion, and metastasis. Therefore, a therapy that combines
      chemotherapeutic drugs with a TME modulator could be a promising route for cancer
      treatment. This paper reports a nanoplatform self-assembled from a hyaluronic
      acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded
      thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME
      and cancer cells. Interestingly, the prodrug HA-PTX can self-assemble on both
      positively and negatively charged liposomes, forming hybrid nanoparticles (HNPs,
      100 nm). Triggered by mild hyperthermia, HA-PTX/MATT-LTSLs HNPs rapidly release
      their payloads into the extracellular environment, and the released HA-PTX
      quickly enters 4T1 cells through a CD44-HA affinity. The HNPs possess promoted
      tumor accumulation (1.6-fold), exhibit deep tumor penetration, and significantly
      inhibit the tumor growth (10-fold), metastasis (100%), and angiogenesis (10
      fold). Importantly, by targeting the TME and maintaining its integrity via
      inhibiting the expression and activity of matrix metalloproteinases (>5-fold),
      blocking the fibroblast activation by downregulating the TGF-beta1 expression (5
      fold) and suppressing the degradation of extracellular matrix, the HNPs allow for
      significant metastasis inhibition. Overall, these findings indicate that a
      prodrug of an HA-hydrophobic-active compound and liposomes can be self-assembled
      into a smart nanoplatform for the dual targeting of the TME and tumor cells and
      efficient combined treatment; additionally, the co-delivery of MATT and HA-PTX
      with the HNPs is a promising approach for the treatment of metastatic cancer.
      This study creates opportunities for fabricating multifunctional nanodevices and
      offers an efficient strategy for disease therapy.

PMID- 29350905
TI  - Ampulexins: A New Family of Peptides in Venom of the Emerald Jewel Wasp, Ampulex
      compressa.
AB  - The parasitoid wasp Ampulex compressa injects venom directly into the brain and
      subesophageal ganglion of the cockroach Periplaneta americana, inducing a 7 to 10
      day lethargy termed hypokinesia. Hypokinesia presents as a significant reduction
      in both escape response and spontaneous walking. We examined aminergic and
      peptidergic components of milked venom with HPLC and MALDI-TOF mass spectrometry.
      HPLC coupled with electrochemical detection confirmed the presence of dopamine in
      milked venom, while mass spectrometry revealed that the venom gland and venom sac
      have distinct peptide profiles, with milked venom predominantly composed of venom
      sac peptides. We isolated and characterized novel alpha-helical, amphipathic
      venom sac peptides that constitute a new family of venom toxins termed
      ampulexins. Injection of the most abundant venom peptide, ampulexin 1, into the
      subesophageal ganglion of cockroaches resulted in a short-term increase in escape
      threshold. Neither milked venom nor venom peptides interfered with growth of
      Escherichia coli or Bacillus thuringiensis on agar plates, and exposure to
      ampulexins or milked venom did not induce cell death in Chinese hamster ovary
      cells (CHO-K1) or Hi5 cells ( Trichoplusia ni).

PMID- 29350906
TI  - Targeted Construction of Light-Harvesting Metal-Organic Frameworks Featuring
      Efficient Host-Guest Energy Transfer.
AB  - Metal-organic frameworks (MOFs) have emerged as promising light-harvesting
      platforms for energy-transfer materials. However, the targeted construction of
      MOFs with desirable photophysical properties and pore structures is still a
      challenge. Herein, 1,1,2,2-tetrakis(4-(pyridin-4-yl)phenyl)ethene (tppe) is
      selected as the ligand for the construction of light-harvesting MOFs due to its
      highly emissive and rigid backbone, which could benefit the light-harvesting
      performance of the MOFs. Three MOFs (MOFs 1-3) were obtained on the basis of
      different metal centers (Zn2+ and Cd2+) and carboxylate building blocks. The
      complete structure characterization of the MOFs helps the illustration of the
      principles for structure tuning of this system. All three MOFs exhibit strong
      tppe-originated photoluminescence emission, with quantum yields as high as 47.6%.
      The fluorescence quantum yield and time-resolved fluorescence studies reveal that
      a remarkable energy-transfer efficiency (up to 96%) was achieved in this system.
      These results clearly indicate tppe-MOFs could be promising light-harvesting
      materials.

PMID- 29350907
TI  - Excitatory and Inhibitory Neuronal Circuits in the Spinal Cord and Their Role in
      the Control of Motor Neuron Function and Degeneration.
AB  - The complex neuronal networks of the spinal cord coordinate a wide variety of
      motor functions, including walking, running, and voluntary and involuntary
      movements. This is accomplished by different groups of neurons, called center
      pattern generators, which control left-right alternation and flexor-extensor
      patterns. These spinal circuits, located in the ventral horns, are formed by
      several neuronal types, and the specific function of most of them has been
      identified by means of studies in vivo and in the isolated spinal cord of mice
      harboring genetically induced ablation of specific neuronal populations. These
      studies have shown that the coordinated activity of several interneuron types,
      mainly GABAergic and glycinergic inhibitory neurons, have a crucial role in the
      modulation of motor neurons activity that finally excites the corresponding
      muscles. A pharmacological experimental approach by administering in the spinal
      cord agonists and antagonists of glutamate, GABA, glycine, and acetylcholine
      receptors to alter their synaptic action has also produced important results,
      linking the deficits in the synaptic function with the resulting motor
      alterations. These results have also increased the knowledge of the mechanisms of
      motor neuron degeneration, which is characteristic of diseases such as
      amyotrophic lateral sclerosis, and therefore open the possibility of designing
      new strategies for the prevention and treatment of these diseases.

PMID- 29350908
TI  - Light Modulation and Water Splitting Enhancement Using a Composite Porous GaN
      Structure.
AB  - On the basis of the laterally porous GaN, we designed and fabricated a composite
      porous GaN structure with both well-ordered lateral and vertical holes. Compared
      to the plane GaN, the composite porous GaN structure with the combination of the
      vertical holes can help to reduce UV reflectance and increase the saturation
      photocurrent during water splitting by a factor of ~4.5. Furthermore, we
      investigated the underlying mechanism for the enhancement of the water splitting
      performance using a finite-difference time-domain method. The results show that
      the well-ordered vertical holes can not only help to open the embedded pore
      channels to the electrolyte at both sides and reduce the migration distance of
      the gas bubbles during the water splitting reactions but also help to modulate
      the light field. Using this composite porous GaN structure, most of the incident
      light can be modulated and trapped into the nanoholes, and thus the electric
      fields localized in the lateral pores can increase dramatically as a result of
      the strong optical coupling. Our findings pave a new way to develop GaN
      photoelectrodes for highly efficient solar water splitting.

PMID- 29350909
TI  - Dual Drug Delivery System Based on Biodegradable Organosilica Core-Shell
      Architectures.
AB  - To overcome drug resistance, efficient cancer therapeutic strategies using a
      combination of small-molecule drugs and macromolecule drugs is highly desired.
      However, because of their significant differences in molecular weight and size,
      it is difficult to load them simultaneously in one vector and to release them
      individually. Here, a biodegradable organosilica-based core-shell-structured
      nanocapsule was designed and used as a dual stimuli-responsive drug vector to
      solve this problem. Biodegradable organosilica shell coated outside the
      macromolecule model drug "core" would be disrupted by high glutathione (GSH)
      levels inside tumor cells, resulting in the escape of the entrapped drugs. Small
      molecule drugs capping on the surface of the organosilica shell via pH-responsive
      imine bonds can be cut and released in the acidic lysosomal environment.
      Transmission electron microscopy has shown that the framework of the organosilica
      shell was dissolved and degraded after 8 h incubation with 5 mM GSH. Confocal
      imaging confirmed that small-molecule and macromolecular drugs were individually
      released from the nanoparticles because of the pH or redox-triggered degradation
      under the tumor microenvironment and thus led to the strong fluorescence recovery
      in the cytoplasm. As expected, these biodegradable organosilica nanoparticles
      could not release drugs into normal cells but could specifically release them
      into tumor cells owing to their tumor-triggered targeting capability. This system
      will serve as an efficient shuttle for multidrug delivery and also provide a
      potential strategy to overcome drug resistance.

PMID- 29350910
TI  - Highly Asymmetric Phase Behaviors of Polyhedral Oligomeric Silsesquioxane-Based
      Multiheaded Giant Surfactants.
AB  - This work reports the molecular design, synthesis, and systematic study on the
      bulk self-assembly behaviors of three series of polyhedral oligomeric
      silsesquioxane (POSS)-based multiheaded giant surfactants XDPOSS-PSn (X = 2, 3,
      and 4), which are composed of two, three, or four hydrophilic hydroxyl-group
      functionalized DPOSS cages attached via one junction point to a hydrophobic
      polystyrene (PS) chain. These series of hybrid polymeric amphiphiles with
      precisely defined chemical structure and controllable molecular architecture are
      synthesized by the sequential usage of "click" reactions. By tuning molecular
      weights of the PS tail, we established full phase diagrams of XDPOSS-PSn as a
      function of the volume fractions of PS chains (VfPS). We found that the self
      assembled structures were greatly influenced by the molecular architecture.
      Strikingly, our results showed that the lamellar morphology, which usually
      existed at relatively symmetric compositions in common diblock copolymers, became
      the thermodynamically stable phase in the 3DPOSS-PSn and 4DPOSS-PSn samples even
      at an asymmetric composition up to VfPS = 0.842, with the ratio between the
      thicknesses of PS and DPOSS lamellae up to 5.32. This unusual phenomenon induced
      by molecular architectural variation could be explained by the large cross
      sectional area of DPOSS cages at the nanophase-separated domain interface and
      high elastic deformation energy of clustered DPOSS cages which have relatively
      rigid conformation. The unique bulk self-assembly behaviors in our POSS-based
      multiheaded giant surfactants provide insights in developing hybrid nanomaterials
      toward unconventional nanostructures.

PMID- 29350912
TI  - Low Temperature-Derived 3D Hexagonal Crystalline Fe3O4 Nanoplates for Water
      Purification.
AB  - Fe3O4 nanoplates were fabricated by an anodic oxidation process and a subsequent
      water assisted crystallization process at low temperature, which was found to be
      very efficient and environmentally friendly. The as-prepared Fe3O4 nanoplates
      have hexagonal outlines with a thickness of about 20 nm. Tremendous grooves were
      distributed on the entire surfaces of the nanoplates, making the two-dimension
      nanoplates have a unique 3D morphology. Transmission electron microscopy results
      confirmed that the single-crystalline nature of the nanoplates was well
      maintained. Owing to the unique structures and porous morphologies, the as
      prepared 3D nanoplates show excellent ability for absorbing solar energy and
      absorbing organic pollutants, which can be utilized for cleaning up water.
      Moreover, the Fe3O4 nanoplates show good magnetic properties that enable them to
      be easily collected and recycled. We believe this study will inspire the
      application of Fe3O4 nanoplates with 3D structures in energy and environmental
      areas.

PMID- 29350911
TI  - A Programmable DNA Origami Platform for Organizing Intrinsically Disordered
      Nucleoporins within Nanopore Confinement.
AB  - Nuclear pore complexes (NPCs) form gateways that control molecular exchange
      between the nucleus and the cytoplasm. They impose a diffusion barrier to
      macromolecules and enable the selective transport of nuclear transport receptors
      with bound cargo. The underlying mechanisms that establish these permeability
      properties remain to be fully elucidated but require unstructured nuclear pore
      proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and
      GLFG. While physical modeling and in vitro approaches have provided a framework
      for explaining how the FG network contributes to the barrier and transport
      properties of the NPC, it remains unknown whether the number and/or the spatial
      positioning of different FG-domains along a cylindrical, ~40 nm diameter
      transport channel contributes to their collective properties and function. To
      begin to answer these questions, we have used DNA origami to build a cylinder
      that mimics the dimensions of the central transport channel and can house a
      specified number of FG-domains at specific positions with easily tunable design
      parameters, such as grafting density and topology. We find the overall morphology
      of the FG-domain assemblies to be dependent on their chemical composition,
      determined by the type and density of FG-repeat, and on their architectural
      confinement provided by the DNA cylinder, largely consistent with here presented
      molecular dynamics simulations based on a coarse-grained polymer model. In
      addition, high-speed atomic force microscopy reveals local and reversible FG
      domain condensation that transiently occludes the lumen of the DNA central
      channel mimics, suggestive of how the NPC might establish its permeability
      properties.

PMID- 29350913
TI  - Environmentally Triggerable Retinoic Acid-Inducible Gene I Agonists Using
      Synthetic Polymer Overhangs.
AB  - Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition
      receptor (PRR) that potently activates antiviral innate immunity upon recognition
      of 5' triphosphorylated double-stranded RNA (pppRNA). Accordingly, RNA ligands of
      the RIG-I pathway have recently emerged as promising antiviral agents, vaccine
      adjuvants, and cancer immunotherapeutics. However, RIG-I is expressed
      constitutively in virtually all cell types, and therefore administration of RIG-I
      agonists causes risk for systemic inflammation and possible dose-limiting
      toxicities. Here, we establish proof-of-concept and initial design criteria for
      pppRNA prodrugs capable of activating the RIG-I pathway in response to specific
      environmental stimuli. We show that covalent conjugation of poly(ethylene glycol)
      (PEG) to the 3' end of the complementary strand, i.e., on the same side but
      opposite strand as the 5' triphosphate group, can generate a synthetic overhang
      that prevents RIG-I activation. Additionally, conjugation of PEG through a
      cleavable linker-here, a reducible disulfide bond-allows for removal of the
      synthetic overhang and restoration of immunostimulatory activity. Furthermore, we
      demonstrate that blockade of RIG-I activation via synthetic overhangs is
      dependent on PEG molecular weight, with a critical molecular weight between 550
      and 1000 Da required to inhibit activity. Additionally, we demonstrate that
      blockade of RIG-I activity is conjugation site-dependent, as ligation of PEG to
      the opposite end of the RNA did not influence ligand activity. Collectively, this
      work demonstrates that conjugation of synthetic polymer overhangs to pppRNA
      through cleavable linkers is a viable strategy for the development of
      environmentally triggerable RIG-I-targeting prodrugs.

PMID- 29350914
TI  - Cys34 Adductomes Differ between Patients with Chronic Lung or Heart Disease and
      Healthy Controls in Central London.
AB  - Oxidative stress generates reactive species that modify proteins, deplete
      antioxidant defenses, and contribute to chronic obstructive pulmonary disease
      (COPD) and ischemic heart disease (IHD). To determine whether protein
      modifications differ between COPD or IHD patients and healthy subjects, we
      performed untargeted analysis of adducts at the Cys34 locus of human serum
      albumin (HSA). Biospecimens were obtained from nonsmoking participants from
      London, U.K., including healthy subjects (n = 20) and patients with COPD (n = 20)
      or IHD (n = 10). Serum samples were digested with trypsin and analyzed by liquid
      chromatography-high resolution mass spectrometry. Effects of air pollution on
      adduct levels were also investigated based on estimated residential exposures to
      PM2.5, O3 and NO2. For the 39 adducts with sufficient data, levels were
      essentially identical in blood samples collected from the same subjects on two
      consecutive days, consistent with the 28 day residence time of HSA. Multivariate
      linear regression revealed 21 significant associations, mainly with the
      underlying diseases but also with air-pollution exposures (p-value < 0.05).
      Interestingly, most of the associations indicated that adduct levels decreased
      with the presence of disease or increased pollutant concentrations. Negative
      associations of COPD and IHD with the Cys34 disulfide of glutathione and two
      Cys34 sulfoxidations, were consistent with previous results from smoking and
      nonsmoking volunteers and nonsmoking women exposed to indoor combustion of coal
      and wood.

PMID- 29350915
TI  - Dichloroimidazolidinedione-Activated Beckmann Rearrangement of Ketoximes for
      Accessing Amides and Lactams.
AB  - A novel protocol for the activation of the Beckmann rearrangement utilizing the
      readily available and economical geminal dichloroimidazolidinediones (DCIDs) on a
      substoichiometric scale (10 mol %) has been developed. A unique self-propagating
      mechanism for the substoichiometric dichloroimidazolidinedione-activated
      transformation was proposed and validated. The substrate scope of the developed
      protocol has been demonstrated by 23 examples with good to excellent yields
      (mostly 90-98%) in a short time (mostly 10-30 min), including a substrate for
      synthesizing the monomer of nylon-12 and a complicated steroidal substrate on a
      preparative scale. This research not only unveils for the first time the
      synthetic potential of substoichiometric amounts of dichloroimidazolidinediones
      in promoting chemical transformation but also offers yet another important
      illustration of the self-propagating cycle in the context of the Beckmann
      rearrangement activated by a structurally novel organic promoter.

PMID- 29350916
TI  - Rhombohedral to Cubic Conversion of GeTe via MnTe Alloying Leads to Ultralow
      Thermal Conductivity, Electronic Band Convergence, and High Thermoelectric
      Performance.
AB  - In this study, a series of Ge1-xMnxTe (x = 0-0.21) compounds were prepared by a
      melting-quenching-annealing process combined with spark plasma sintering (SPS).
      The effect of alloying MnTe into GeTe on the structure and thermoelectric
      properties of Ge1-xMnxTe is profound. With increasing content of MnTe, the
      structure of the Ge1-xMnxTe compounds gradually changes from rhombohedral to
      cubic, and the known R3m to Fm-3m phase transition temperature of GeTe moves from
      700 K closer to room temperature. First-principles density functional theory
      calculations show that alloying MnTe into GeTe decreases the energy difference
      between the light and heavy valence bands in both the R3m and Fm-3m structures,
      enhancing a multiband character of the valence band edge that increases the hole
      carrier effective mass. The effect of this band convergence is a significant
      enhancement in the carrier effective mass from 1.44 m0 (GeTe) to 6.15 m0
      (Ge0.85Mn0.15Te). In addition, alloying with MnTe decreases the phonon relaxation
      time by enhancing alloy scattering, reduces the phonon velocity, and increases Ge
      vacancies all of which result in an ultralow lattice thermal conductivity of 0.13
      W m-1 K-1 at 823 K. Subsequent doping of the Ge0.9Mn0.1Te compositions with Sb
      lowers the typical very high hole carrier concentration and brings it closer to
      its optimal value enhancing the power factor, which combined with the ultralow
      thermal conductivity yields a maximum ZT value of 1.61 at 823 K (for
      Ge0.86Mn0.10Sb0.04Te). The average ZT value of the compound over the temperature
      range 400-800 K is 1.09, making it the best GeTe-based thermoelectric material.

PMID- 29350918
TI  - Entrapped Styrene Butadiene Polymer Chains by Sol-Gel-Derived Silica
      Nanoparticles with Hierarchical Raspberry Structures.
AB  - A sol-gel transformation of liquid silica precursor to solid silica particles was
      carried out in a one-pot synthesis way, where a solution of styrene butadiene
      elastomer was present. The composites, thus produced, offered remarkable
      improvements of mechanical and dynamic mechanical performances compared to
      precipitated silica. The morphological analysis reveals that the alkoxy-based
      silica particles resemble a raspberry structure when the synthesis of the silica
      was carried out in the presence of polymer molecules and represent a much more
      open silica-network structure. However, in the absence of the polymer, the
      morphology of the silica particles is found to be different. It is envisaged that
      the special morphology of the in situ synthesized silica particles contributes to
      the superior reinforcement effects, which are associated with a strong silica
      rubber interaction by rubber chains trapped inside the raspberry-like silica
      aggregates. Therefore, the interfaces are characterized in detail by low-field
      solid-state 1H NMR spectroscopy, 29Si solid-state NMR spectroscopy, and energy
      dispersive X-ray spectroscopy. Low-field 1H NMR-based double-quantum experiments
      provide a quantitative information about the cross-link density of the silica
      filled rubber composites and about the influence of silane coupling agent on the
      chemical cross-link density of the network and correlates well with equilibrium
      swelling measurements. The special microstructure of the alkoxy-based silica was
      found to be associated with the interaction between alkoxy-based silica and
      rubber chains as a consequence of particle growth in the presence of rubber
      chains.

PMID- 29350919
TI  - Pair Distribution Function Analysis of Structural Disorder by Nb5+ Inclusion in
      Ceria: Evidence for Enhanced Oxygen Storage Capacity from Under-Coordinated
      Oxide.
AB  - Partial substitution of Ce4+ by Nb5+ is possible in CeO2 by coinclusion of Na+ to
      balance the charge, via hydrothermal synthesis in sodium hydroxide solution. Pair
      distribution function analysis using reverse Monte Carlo refinement reveals that
      the small pentavalent substituent resides in irregular coordination positions in
      an average fluorite lattice, displaced away from the ideal cubic coordination
      toward four oxygens. This results in under-coordinated oxygen, which explains
      significantly enhanced oxygen storage capacity of the materials of relevance to
      redox catalysis used in energy and environmental applications.

PMID- 29350920
TI  - Crystal Structures and Human Leukemia Cell Apoptosis Inducible Activities of
      Parthenolide Analogues Isolated from Piptocoma rufescens.
AB  - The molecular structures of three parthenolide analogues, (-)-goyazensolide (1),
      (-)-15-deoxygoyazensolide (2), and (-)-ereglomerulide (3), isolated from the
      leaves of Piptocoma rufescens in a previous study were determined by X-ray
      analysis, and the absolute configuration of (-)-goyazensolide (1) was confirmed
      crystallographically using Cu Kalpha radiation at low temperature. Compounds 1-3,
      (+)-rufesolide A (4), and commercial parthenolide were found to be growth
      inhibitory toward MOLM-13 and EOL-1 human acute myeloid leukemia cells using
      PKC412 (midostaurin) as the positive control, with 1-3 being more active than
      parthenolide. Also, compounds 1-4 exhibited synergistic effects when tested with
      PKC412, but parthenolide did not show this type of activity. At a concentration
      lower than 2.0 MUM, both 1 and 2 induced approximately 50% of the cells to become
      apoptotic at a late stage of the cell cycle, but no similar apoptotic effects
      were observed for 3, 4, or parthenolide. Leukemia cell apoptosis was induced by
      these compounds through the activation of caspase-3 and the inhibition of NF
      kappaB, as indicated by immunoblotting analysis, and compounds 1 and 2 seem to be
      promising leads for development as potential antileukemic agents.

PMID- 29350917
TI  - Oxygen Activation and Energy Conservation by Cytochrome c Oxidase.
AB  - This review focuses on the type A cytochrome c oxidases (C cO), which are found
      in all mitochondria and also in several aerobic bacteria. C cO catalyzes the
      respiratory reduction of dioxygen (O2) to water by an intriguing mechanism, the
      details of which are fairly well understood today as a result of research for
      over four decades. Perhaps even more intriguingly, the membrane-bound C cO
      couples the O2 reduction chemistry to translocation of protons across the
      membrane, thus contributing to generation of the electrochemical proton gradient
      that is used to drive the synthesis of ATP as catalyzed by the rotary ATP
      synthase in the same membrane. After reviewing the structure of the core subunits
      of C cO, the active site, and the transfer paths of electrons, protons, oxygen,
      and water, we describe the states of the catalytic cycle and point out the few
      remaining uncertainties. Finally, we discuss the mechanism of proton
      translocation and the controversies in that area that still prevail.

PMID- 29350922
TI  - Computing Curvature Sensitivity of Biomolecules in Membranes by Simulated
      Buckling.
AB  - Membrane curvature sensing, where the binding free energies of membrane
      associated molecules depend on the local membrane curvature, is a key factor to
      modulate and maintain the shape and organization of cell membranes. However, the
      microscopic mechanisms are not well understood, partly due to absence of
      efficient simulation methods. Here, we describe a method to compute the curvature
      dependence of the binding free energy of a membrane-associated probe molecule
      that interacts with a buckled membrane, which has been created by lateral
      compression of a flat bilayer patch. This buckling approach samples a wide range
      of curvatures in a single simulation, and anisotropic effects can be extracted
      from the orientation statistics. We develop an efficient and robust algorithm to
      extract the motion of the probe along the buckled membrane surface, and evaluate
      its numerical properties by extensive sampling of three coarse-grained model
      systems: local lipid density in a curved environment for single-component
      bilayers, curvature preferences of individual lipids in two-component membranes,
      and curvature sensing by a homotrimeric transmembrane protein. The method can be
      used to complement experimental data from curvature partition assays and provides
      additional insight into mesoscopic theories and molecular mechanisms for
      curvature sensing.

PMID- 29350921
TI  - The Semireduced Mechanism for Nitric Oxide Reduction by Non-Heme Diiron
      Complexes: Modeling Flavodiiron Nitric Oxide Reductases.
AB  - Flavodiiron nitric oxide reductases (FNORs) are a subclass of flavodiiron
      proteins (FDPs) capable of preferential binding and subsequent reduction of NO to
      N2O. FNORs are found in certain pathogenic bacteria, equipping them with
      resistance to nitrosative stress, generated as a part of the immune defense in
      humans, and allowing them to proliferate. Here, we report the spectroscopic
      characterization and detailed reactivity studies of the diiron dinitrosyl model
      complex [Fe2(BPMP)(OPr)(NO)2](OTf)2 for the FNOR active site that is capable of
      reducing NO to N2O [Zheng et al., J. Am. Chem. Soc. 2013, 135, 4902-4905]. Using
      UV-vis spectroscopy, cyclic voltammetry, and spectro-electrochemistry, we show
      that one reductive equivalent is in fact sufficient for the quantitative
      generation of N2O, following a semireduced reaction mechanism. This reaction is
      very efficient and produces N2O with a first-order rate constant k > 102 s-1.
      Further isotope labeling studies confirm an intramolecular N-N coupling
      mechanism, consistent with the rapid time scale of the reduction and a very low
      barrier for N-N bond formation. Accordingly, the reaction proceeds at -80 
      degrees C, allowing for the direct observation of the mixed-valent product of the
      reaction. At higher temperatures, the initial reaction product is unstable and
      decays, ultimately generating the diferrous complex [Fe2(BPMP)(OPr)2](OTf) and an
      unidentified ferric product. These results combined offer deep insight into the
      mechanism of NO reduction by the relevant model complex [Fe2(BPMP)(OPr)(NO)2]2+
      and provide direct evidence that the semireduced mechanism would constitute a
      highly efficient pathway to accomplish NO reduction to N2O in FNORs and in
      synthetic catalysts.

PMID- 29350923
TI  - CASSCF Calculations Reveal Competitive Chair (Pericyclic) and Boat
      (Pseudopericyclic) Transition States for the [3,3] Sigmatropic Rearrangement of
      Allyl Esters.
AB  - (10,8)CASPT2/6-31G**//(10,8)CASSCF/6-31G** and CCSD(T)/cc-pVDZ//(10,8)-CASSCF/6
      31G** calculations have been performed on the potential surface for the [3,3]
      sigmatropic allyl ester rearrangements of cis-3-penten-2-yl acetate (16) to trans
      3-penten-2-yl acetate (17) and 3-buten-2-yl acetate (21) to trans-2-buten-1-yl
      acetate (22). The results are compared to DFT (B3LYP/6-31G**) calculations on the
      known 16 -> 17 rearrangement that reported it to be concerted and
      pseudopericyclic through a boat-shaped transition structure ( Birney, D. M. et
      al. J. Am. Chem. Soc. 2009 , 131 , 528 - 537 ). The CASSCF calculations, on the
      other hand, uncovered competitive concerted pathways for both the 16 -> 17 and 21
      -> 22 rearrangements, though it was necessary to apply certain approximations in
      the former case. While one CASSCF pathway in each case involves a boat-shaped
      transition structure, similar to the one located through DFT calculations, the
      other pathway involves a chair-shaped transition structure. Preference for chair
      or boat is shown to be method dependent. Moreover, examination of the CASSCF
      active-space orbitals clearly confirms that the boat-shaped transition structures
      are pseudopericyclic but significantly also established that the chair-shaped
      transition structures are clearly pericyclic. Conclusions based on these results,
      and regarding our understanding of pericyclic vs pseudopericyclic reactions, are
      proffered.

PMID- 29350924
TI  - Influences of Bifunctional PNP-Pincer Ligands on Low Valent Cobalt Complexes
      Relevant to CO2 Hydrogenation.
AB  - Pincer ligated coordination complexes bearing bifunctional sites have been at the
      center of recent developments in reversible hydrogenation catalysis, especially
      in cases utilizing base metals. The influence of bifunctional ligands on low
      valent cobalt complexes is detailed here using comparisons between the PNP-pincer
      ligands MeN[CH2CH2(PR2)]2 and HN[CH2CH2(PR2)]2 (R = iPr, Cy). Comparative
      catalytic studies of CO2 hydrogenation show that cobalt(I) precatalysts bearing
      the tertiary amine ligand dramatically outperform those bearing the secondary
      amine pincer ligand. Despite strong similarities between the precatalyst ground
      state structure and the redox potentials of the two systems, ligand
      bifunctionality was found to be detrimental to catalyst productivity. The
      enhanced stability imparted by the MeN[CH2CH2(PR2)]2 ligand also enabled
      isolation and characterization of a zero-valent cobalt dicarbonyl species, which
      was used to study the catalytically active oxidation state of cobalt in CO2
      hydrogenation.

PMID- 29350925
TI  - Exposure to Dietary Methyl-Mercury Solely during Embryonic and Juvenile
      Development Halves Subsequent Reproductive Success in Adult Zebra Finches.
AB  - Long-term exposure to methyl-mercury has deleterious effects on avian
      reproduction. However, little is known about whether exposure to mercury solely
      during embryonic and juvenile development can have long-lasting effects on
      subsequent reproductive performance as adults. Birds that hatch on contaminated
      sites but disperse elsewhere will be exposed only during development. Hence, it
      is important to understand the reproductive consequences of avian exposure to
      methyl-mercury during early life. Accordingly, in this experiment, domesticated
      zebra finches ( Taeniopygia guttata) were exposed to dietary methyl-mercury (1.20
      MUg/g wet weight) from conception through independence (50 days post-hatching).
      Following maturity, developmentally exposed and control finches were paired
      within treatment groups and allowed to breed repeatedly for 8 months.
      Developmentally exposed pairs hatched 32% fewer eggs and produced 50% fewer
      independent juveniles despite transferring only traces of mercury into their
      offspring. This is the first example of mercury-related reproductive declines in
      birds not exposed to mercury during breeding. The magnitude of reproductive
      decline was similar to that of zebra finches exposed to methyl-mercury during the
      breeding process. Bird populations breeding in contaminated habitats may suffer
      from a 2-fold fitness cost of mercury exposure; adult exposure compromises
      parents' reproduction, while offspring exposure results in reduced reproduction
      in the next generation.

PMID- 29350926
TI  - Concentrations and Migratabilities of Hazardous Elements in Second-Hand
      Children's Plastic toys.
AB  - About 200 second-hand plastic toys sourced in the UK have been analyzed by X-ray
      fluorescence spectrometry for hazardous elements (As, Ba, Cd, Cr, Hg, Pb, Sb, Se)
      and Br as a proxy for brominated flame retardants. Each element was detected in
      >20 toys or components thereof with the exception of As, Hg, and Se, with the
      frequent occurrence of Br, Cd, and Pb and at maximum concentrations of about
      16000, 20000, and 5000 MUg g-1, respectively, of greatest concern from a
      potential exposure perspective. Migration was evaluated on components of 26 toys
      under simulated stomach conditions (0.07 M HCl) with subsequent analysis by
      inductively coupled plasma spectrometry. In eight cases, Cd or Pb exceeded their
      migration limits as stipulated by the current EU Toy Safety Directive (17 and 23
      MUg g-1, respectively), with Cd released from yellow and red Lego bricks
      exceeding its limit by 1 order of magnitude. Two further cases were potentially
      noncompliant based on migratable Cr, with one item also containing >250 MUg g-1
      migratable Br. While there is no retroactive regulation on second-hand toys,
      consumers should be aware that old, mouthable, plastic items may present a source
      of hazardous element exposure to infants.

PMID- 29350927
TI  - Synthesis and Pharmacological Characterization of C4beta-Amide-Substituted 2
      Aminobicyclo[3.1.0]hexane-2,6-dicarboxylates. Identification of (1 S,2 S,4 S,5
      R,6 S)-2-Amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic
      Acid (LY2794193), a Highly Potent and Selective mGlu3 Receptor Agonist.
AB  - Multiple therapeutic opportunities have been suggested for compounds capable of
      selective activation of metabotropic glutamate 3 (mGlu3) receptors, but small
      molecule tools are lacking. As part of our ongoing efforts to identify potent,
      selective, and systemically bioavailable agonists for mGlu2 and mGlu3 receptor
      subtypes, a series of C4beta-N-linked variants of (1 S,2 S,5 R,6 S)-2-amino
      bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 1 (LY354740) were prepared and
      evaluated for both mGlu2 and mGlu3 receptor binding affinity and functional
      cellular responses. From this investigation we identified (1 S,2 S,4 S,5 R,6 S)-2
      amino-4-[(3-methoxybenzoyl)amino]bicyclo[3.1.0]hexane-2,6-dicarboxylic acid 8p
      (LY2794193), a molecule that demonstrates remarkable mGlu3 receptor selectivity.
      Crystallization of 8p with the amino terminal domain of hmGlu3 revealed critical
      binding interactions for this ligand with residues adjacent to the glutamate
      binding site, while pharmacokinetic assessment of 8p combined with its effect in
      an mGlu2 receptor-dependent behavioral model provides estimates for doses of this
      compound that would be expected to selectively engage and activate central mGlu3
      receptors in vivo.

PMID- 29350928
TI  - A Comparative Investigation of Proton Conductivities for Two Metal-Organic
      Frameworks under Water and Aqua-Ammonia Vapors.
AB  - Our investigation on the proton conductivities of two water-stable isostructural
      3D Co(II) MOFs, {[Co3(DMPhIDC)2(H2O)6].2H2O}n (1) [DMPhH3IDC = 2-(3,4
      dimethylphenyl)-imidazole-4,5-dicarboxylic acid] and {[Co3(m
      BrPhIDC)2(H2O)6].2H2O} (2) [m-BrPhH3IDC = 2-(m-bromophenyl)-imidazole-4,5
      dicarboxylic acid], under water or aqua-ammonia vapor shows that the optimized
      proton conductivities of both 1 and 2 under aqua-ammonia vapor are 4.41 * 10-3
      S.cm-1 and 5.07 * 10-4 S.cm-1 (at aqua-ammonia vapor from 1.5 M NH3.H2O solution
      and 100  degrees C), respectively, which are approximately 1 order of magnitude
      greater than those maximum values (8.91 * 10-4 S.cm-1 and 7.64 * 10-5 S.cm-1)
      under water vapor (at 98% RH and 100  degrees C). The plausible proton pathways
      and mechanisms of the MOFs have been proposed in terms of the structural
      analyses, activation energy calculations, water and NH3 vapor absorptions, and
      PXRD determinations.

PMID- 29350929
TI  - Veterinary Drugs in the Environment: Current Knowledge and Challenges for the
      Future.

PMID- 29350930
TI  - Curtin-Hammett-Driven Intramolecular Cyclization of Heteroenyne-Allenes to
      Phenanthridine-Fused Quinazoliniminiums.
AB  - Intramolecular cyclization of the heteroenyne-allene 2-((biphenyl-2
      ylimino)methyleneamino)benzonitrile 1 to phenanthridine-fused quinazoliniminium
      salt PQ in the presence of a Lewis acid at room temperature involves formation of
      two new bonds: a C-C bond and a C-N bond. In this article, density functional
      theory (B3LYP and M06-2X) was employed in conjunction with 6-311G* basis set to
      gain insights into the mechanism of this cyclization reaction. The solvent
      effects were considered using Polarizable Continuum Model with nitromethane as
      the solvent. Our calculations show that C-C bond formation precedes the C-N bond
      formation. Precisely, the mechanism involves initial protonation of 1 at Nalpha
      and Nbeta of the carbodiimide to form rapidly equilibrating conformers of the
      tautomers 2a,b and 3a,b. The Curtin-Hammett principle is invoked to determine the
      course of the reaction from these protonated species, which predicts that the
      intramolecular Friedel-Crafts type N-acylation (C-C bond formation) occurs
      between the protonated carbodiimide and biphenyl ring of the isomer 3b to form
      phenanthridinium cation 6b via transition state TS3b6b. Once 6b is formed, it
      converts to its most stable tautomers 8R and 9a. Once again, the Curtin-Hammett
      principle suggests that intramolecular nucleophilic attack is preferred from the
      tautomer 8R, where phenanthridine N-atom (Nbeta) attacks the protonated nitrile
      group (C-N bond formation) and results in the formation of intermediate 11 via
      TS8R11. 11 then tautomerizes to the most stable cation 13. The coordination of
      the latter with the chloride anion yields the phenanthridine-fused heterocyclic
      salt PQ with overall release of energy. The pathways involving protonation at the
      nitrile (Ngamma) of 1 were found to be energetically unfavorable and thus
      insignificant to the mechanism of cyclization.

PMID- 29350931
TI  - Multiscale and Multistep Ordering of Flow-Induced Nucleation of Polymers.
AB  - Flow-induced crystallization (FIC) is a typical nonequilibrium phase transition
      and a core industry subject for the largest group of commercially useful
      polymeric materials: semicrystalline polymers. A fundamental understanding of FIC
      can benefit the research of nonequilibrium ordering in matter systems and help to
      tailor the ultimate properties of polymeric materials. Concerning the
      crystallization process, flow can accelerate the kinetics by orders of magnitude
      and induce the formation of oriented crystallites like shish-kebab, which are
      associated with the major influences of flow on nucleation, that is, raised
      nucleation density and oriented nuclei. The topic of FIC has been studied for
      more than half a century. Recently, there have been many developments in
      experimental approaches, such as synchrotron radiation X-ray scattering,
      ultrafast X-ray detectors with a time resolution down to the order of
      milliseconds, and novel laboratory devices to mimic the severe flow field close
      to real processing conditions. By a combination of these advanced methods, the
      evolution process of FIC can be revealed more precisely (with higher time
      resolution and on more length scales) and quantitatively. The new findings are
      challenging the classical interpretations and theories that were mostly derived
      from quiescent or mild-flow conditions, and they are triggering the
      reconsideration of FIC foundations. This review mainly summarizes experimental
      results, advances in physical understanding, and discussions on the multiscale
      and multistep nature of oriented nuclei induced by strong flow. The multiscale
      structures include segmental conformation, packing of conformational ordering,
      deformation on the whole-chain scale, and macroscopic aggregation of
      crystallites. The multistep process involves conformation transition, isotropic
      nematic transition, density fluctuation (or phase separation), formation of
      precursors, and shish-kebab crystallites, which are possible ordering processes
      during nucleation. Furthermore, some theoretical progress and modeling efforts
      are also included.

PMID- 29350932
TI  - Dinuclear Ag(I) Complex Designed for Highly Efficient Thermally Activated Delayed
      Fluorescence.
AB  - The dinuclear Ag(I) complex has been designed to show thermally activated delayed
      fluorescence (TADF) of high efficiency. Strongly electron-donating terminal
      ligands are introduced to destabilize the d orbitals of the Ag+ ions.
      Consequently, the orbitals distinctly contribute to the HOMO, whereas the LUMO is
      localized on the bridging ligand. This ensures charge transfer character of the
      lowest excited singlet S1 and triplet T1 states. Accordingly, a small energy gap
      DeltaE(S1-T1) is obtained, being essential for TADF behavior. Photophysical
      investigations show that at ambient temperature the complex exhibits TADF
      reaching a quantum yield of PhiPL = 70% with the decay time of only tau = 1.9
      MUs, manifesting one of the fastest TADF decays observed so far. Such an
      outstanding TADF efficiency is based on a small value of DeltaE(S1-T1) = 480 cm-1
      combined with a large transition rate of k(S1 -> S0) = 2.2 * 107 s-1.

PMID- 29350933
TI  - Reproducing the Ensemble Average Polar Solvation Energy of a Protein from a
      Single Structure: Gaussian-Based Smooth Dielectric Function for Macromolecular
      Modeling.
AB  - Typically, the ensemble average polar component of solvation energy
      (DeltaGpolarsolv) of a macromolecule is computed using molecular dynamics (MD) or
      Monte Carlo (MC) simulations to generate conformational ensemble and then
      single/rigid conformation solvation energy calculation is performed on each
      snapshot. The primary objective of this work is to demonstrate that Poisson
      Boltzmann (PB)-based approach using a Gaussian-based smooth dielectric function
      for macromolecular modeling previously developed by us (Li et al. J. Chem. Theory
      Comput. 2013, 9 (4), 2126-2136) can reproduce that ensemble average
      (DeltaGpolarsolv) of a protein from a single structure. We show that the Gaussian
      based dielectric model reproduces the ensemble average
      DeltaGpolarsolv(?DeltaGpolarsolv?) from an energy-minimized structure of a
      protein regardless of the minimization environment (structure minimized in vacuo,
      implicit or explicit waters, or crystal structure); the best case, however, is
      when it is paired with an in vacuo-minimized structure. In other minimization
      environments (implicit or explicit waters or crystal structure), the traditional
      two-dielectric model can still be selected with which the model produces correct
      solvation energies. Our observations from this work reflect how the ability to
      appropriately mimic the motion of residues, especially the salt bridge residues,
      influences a dielectric model's ability to reproduce the ensemble average value
      of polar solvation free energy from a single in vacuo-minimized structure.

PMID- 29350934
TI  - A Molecular Electron Density Theory Study of the Reactivity and Selectivities in
      [3 + 2] Cycloaddition Reactions of C,N-Dialkyl Nitrones with Ethylene
      Derivatives.
AB  - The zw-type [3 + 2] cycloaddition (32CA) reactions of C,N-dialkyl nitrones with a
      series of ethylenes of increased electrophilic character have been studied within
      the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p)
      computational level. Both, reactivity and selectivities are rationalized
      depending on the polar character of the reaction. Due to the strong nucleophilic
      character of C,N-dialkyl nitrones, the corresponding zw-type 32CA reactions are
      accelerated with the increased electrophilic character of the ethylene, which
      also plays a crucial role in the reaction mechanism, thus determining the regio-
      and stereoselectivities experimentally observed. While, in the 32CA reactions
      with nucleophilic ethylenes, the reaction begins with the formation of the C-C
      single bond, determining the ortho regioselectivity, in the 32CA reactions with
      strong electrophilic ethylenes, the reaction begins with the formation of the C-O
      single bond involving the beta-conjugated carbon of the ethylene, determining the
      meta regioselectivity. The present MEDT study also provides an explanation for
      the unexpected ortho regioselectivity experimentally found in the 32CA reactions
      involving weak electrophilic ethylenes such as ethyl acrylate and acrylonitrile.

PMID- 29350935
TI  - Reconfigurable Skyrmion Logic Gates.
AB  - Magnetic skyrmion, a nanosized spin texture with topological property, has become
      an area of significant interest due to the scientific insight that it can provide
      and also its potential impact on applications such as ultra-low-energy and ultra
      high-density logic gates. In the quest for the reconfiguration of single logic
      device and the implementation of the complete logic functions, a novel
      reconfigurable skyrmion logic (RSL) is proposed and verified by micromagnetic
      simulations. Logic functions including AND, OR, NOT, NAND, NOR, XOR, and XNOR are
      implemented in the ferromagnetic (FM) nanotrack by virtue of various effects
      including spin orbit torque, skyrmion Hall effect, skyrmion-edge repulsions, and
      skyrmion-skyrmion collision. Different logic functions can be selected in an RSL
      by applying voltage to specific region(s) of the device, changing the local
      anisotropy energy of FM film. Material properties and geometrical scaling studies
      suggest RSL gates fit for energy-efficient computing as well as provide the
      guidelines for the design and optimization of this new logic family.

PMID- 29350937
TI  - Light Stops at Exceptional Points.
AB  - Almost twenty years ago, light was slowed down to less than 10^{-7} of its vacuum
      speed in a cloud of ultracold atoms of sodium. Upon a sudden turn-off of the
      coupling laser, a slow light pulse can be imprinted on cold atoms such that it
      can be read out and converted into a photon again. In this process, the light is
      stopped by absorbing it and storing its shape within the atomic ensemble.
      Alternatively, the light can be stopped at the band edge in photonic-crystal
      waveguides, where the group speed vanishes. Here, we extend the phenomenon of
      stopped light to the new field of parity-time (PT) symmetric systems. We show
      that zero group speed in PT symmetric optical waveguides can be achieved if the
      system is prepared at an exceptional point, where two optical modes coalesce.
      This effect can be tuned for optical pulses in a wide range of frequencies and
      bandwidths, as we demonstrate in a system of coupled waveguides with gain and
      loss.

PMID- 29350938
TI  - Cyclotron Orbits of Composite Fermions in the Fractional Quantum Hall Regime.
AB  - We study a bilayer GaAs hole system that hosts two distinct many-body phases at
      low temperatures and high perpendicular magnetic fields. The higher-density (top)
      layer develops a Fermi sea of composite fermions (CFs) in its half-filled lowest
      Landau level, while the lower-density (bottom) layer forms a Wigner crystal (WC)
      as its filling becomes very small. Owing to the interlayer interaction, the CFs
      in the top layer feel the periodic Coulomb potential of the WC in the bottom
      layer. We measure the magnetoresistance of the top layer while changing the
      bottom-layer density. As the WC layer density increases, the resistance peaks
      separating the adjacent fractional quantum Hall states in the top layer change
      nonmonotonically and attain maximum values when the cyclotron orbit of the CFs
      encloses one WC lattice point. These features disappear at T=275  mK when the WC
      melts. The observation of such geometric resonance features is unprecedented and
      surprising as it implies that the CFs retain a well-defined cyclotron orbit and
      Fermi wave vector even deep in the fractional quantum Hall regime, far from half
      filling.

PMID- 29350939
TI  - Mirror Anomaly in Dirac Semimetals.
AB  - We demonstrate that, apart from the chiral anomaly, Dirac semimetals possess
      another quantum anomaly, which we call the mirror anomaly and which manifests in
      a singular response of the Dirac semimetal to an applied magnetic field. Namely,
      the anomalous Hall conductivity exhibits step-function singularities when the
      field is rotated. We show that this phenomenon is closely analogous to the parity
      anomaly of (2+1)-dimensional Dirac fermions, but with mirror symmetry, which we
      demonstrate emerges near any Dirac point at a time reversal invariant momentum,
      replacing the parity symmetry.

PMID- 29350940
TI  - Experimental Verification of a Jarzynski-Related Information-Theoretic Equality
      by a Single Trapped Ion.
AB  - Most nonequilibrium processes in thermodynamics are quantified only by
      inequalities; however, the Jarzynski relation presents a remarkably simple and
      general equality relating nonequilibrium quantities with the equilibrium free
      energy, and this equality holds in both the classical and quantum regimes. We
      report a single-spin test and confirmation of the Jarzynski relation in the
      quantum regime using a single ultracold ^{40}Ca^{+} ion trapped in a harmonic
      potential, based on a general information-theoretic equality for a temporal
      evolution of the system sandwiched between two projective measurements. By
      considering both initially pure and mixed states, respectively, we verify, in an
      exact and fundamental fashion, the nonequilibrium quantum thermodynamics relevant
      to the mutual information and Jarzynski equality.

PMID- 29350941
TI  - Immotile Active Matter: Activity from Death and Reproduction.
AB  - Unlike equilibrium atomic solids, biofilms-soft solids composed of bacterial
      cells-do not experience significant thermal fluctuations at the constituent
      level. However, living cells stochastically reproduce and die, provoking a
      mechanical response. We investigate the mechanical consequences of cellular death
      and reproduction by measuring surface-height fluctuations of biofilms containing
      two mutually antagonistic strains of Vibrio cholerae that kill one another on
      contact via the type VI secretion system. While studies of active matter
      typically focus on activity via constituent mobility, here, activity is mediated
      by reproduction and death events in otherwise immobilized cells. Biofilm surface
      topography is measured in the nearly homeostatic limit via white light
      interferometry. Although biofilms are far from equilibrium systems, measured
      surface-height fluctuation spectra resemble the spectra of thermal permeable
      membranes but with an activity-mediated effective temperature, as predicted by
      Risler, Peilloux, and Prost [Phys. Rev. Lett. 115, 258104 (2015)PRLTAO0031
      900710.1103/PhysRevLett.115.258104]. By comparing the activity of killer strains
      of V. cholerae with that of genetically modified strains that cannot kill each
      other and validating with individual-based simulations, we demonstrate that
      extracted effective temperatures increase with the amount of death and
      reproduction and that death and reproduction can fluidize biofilms. Together,
      these observations demonstrate the unique physical consequences of activity
      mediated by death and reproduction events.

PMID- 29350942
TI  - Shrinking of Rapidly Evaporating Water Microdroplets Reveals their Extreme
      Supercooling.
AB  - The fast evaporative cooling of micrometer-sized water droplets in a vacuum
      offers the appealing possibility to investigate supercooled water-below the
      melting point but still a liquid-at temperatures far beyond the state of the art.
      However, it is challenging to obtain a reliable value of the droplet temperature
      under such extreme experimental conditions. Here, the observation of morphology
      dependent resonances in the Raman scattering from a train of perfectly uniform
      water droplets allows us to measure the variation in droplet size resulting from
      evaporative mass losses with an absolute precision of better than 0.2%. This
      finding proves crucial to an unambiguous determination of the droplet
      temperature. In particular, we find that a fraction of water droplets with an
      initial diameter of 6379+/-12  nm remain liquid down to 230.6+/-0.6  K. Our
      results question temperature estimates reported recently for larger supercooled
      water droplets and provide valuable information on the hydrogen-bond network in
      liquid water in the hard-to-access deeply supercooled regime.

PMID- 29350943
TI  - Single-Atom Transistor as a Precise Magnetic Field Sensor.
AB  - Feshbach resonances, which allow for tuning the interactions of ultracold atoms
      with an external magnetic field, have been widely used to control the properties
      of quantum gases. We propose a scheme for using scattering resonances as a probe
      for external fields, showing that by carefully tuning the parameters it is
      possible to reach a 10^{-5}  G (or nT) level of precision with a single pair of
      atoms. We show that, for our collisional setup, it is possible to saturate the
      quantum precision bound with a simple measurement protocol.

PMID- 29350945
TI  - Controlled-phase Gate for Photons Based on Stationary Light.
AB  - We propose a method to induce strong effective interactions between photons
      mediated by an atomic ensemble. To achieve this, we use the so-called stationary
      light effect to enhance the interaction. Regardless of the single-atom coupling
      to light, the interaction strength between the photons can be enhanced by
      increasing the total number of atoms. For sufficiently many atoms, the setup can
      be viable as a controlled-phase gate for photons. We derive analytical
      expressions for the fidelities for two modes of gate operation: deterministic and
      heralded conditioned on the presence of two photons at the output.

PMID- 29350946
TI  - Electrical Control of Structural and Physical Properties via Strong Spin-Orbit
      Interactions in Sr_{2}IrO_{4}.
AB  - Electrical control of structural and physical properties is a long-sought, but
      elusive goal of contemporary science and technology. We demonstrate that a
      combination of strong spin-orbit interactions (SOI) and a canted
      antiferromagnetic Mott state is sufficient to attain that goal. The
      antiferromagnetic insulator Sr_{2}IrO_{4} provides a model system in which strong
      SOI lock canted Ir magnetic moments to IrO_{6} octahedra, causing them to rigidly
      rotate together. A novel coupling between an applied electrical current and the
      canting angle reduces the Neel temperature and drives a large, nonlinear lattice
      expansion that closely tracks the magnetization, increases the electron mobility,
      and precipitates a unique resistive switching effect. Our observations open new
      avenues for understanding fundamental physics driven by strong SOI in condensed
      matter, and provide a new paradigm for functional materials and devices.

PMID- 29350947
TI  - 4f Crystal Field Ground State of the Strongly Correlated Topological Insulator
      SmB_{6}.
AB  - We investigated the crystal-electric field ground state of the 4f manifold in the
      strongly correlated topological insulator SmB_{6} using core-level nonresonant
      inelastic x-ray scattering. The directional dependence of the scattering function
      that arises from higher multipole transitions establishes unambiguously that the
      Gamma_{8} quartet state of the Sm f^{5}  J=5/2 configuration governs the ground
      state symmetry and, hence, the topological properties of SmB_{6}. Our findings
      contradict the results of density functional calculations reported so far.

PMID- 29350948
TI  - Evolution of Temporal Coherence in Confined Exciton-Polariton Condensates.
AB  - We study the influence of spatial confinement on the second-order temporal
      coherence of the emission from a semiconductor microcavity in the strong coupling
      regime. The confinement, provided by etched micropillars, has a favorable impact
      on the temporal coherence of solid state quasicondensates that evolve in our
      device above threshold. By fitting the experimental data with a microscopic
      quantum theory based on a quantum jump approach, we scrutinize the influence of
      pump power and confinement and find that phonon-mediated transitions are enhanced
      in the case of a confined structure, in which the modes split into a discrete
      set. By increasing the pump power beyond the condensation threshold, temporal
      coherence significantly improves in devices with increased spatial confinement,
      as revealed in the transition from thermal to coherent statistics of the emitted
      light.

PMID- 29350949
TI  - Collective Longitudinal Polarization in Relativistic Heavy-Ion Collisions at Very
      High Energy.
AB  - We study the polarization of particles in relativistic heavy-ion collisions at
      very high energy along the beam direction within a relativistic hydrodynamic
      framework. We show that this component of the polarization decreases much slower
      with center-of-mass energy compared to the transverse component, even in the
      ideal longitudinal boost-invariant scenario with nonfluctuating initial state,
      and that it can be measured by taking advantage of its quadrupole structure in
      the transverse momentum plane. In the ideal longitudinal boost-invariant
      scenario, the polarization is proportional to the gradient of temperature at the
      hadronization and its measurement can provide important information about the
      cooling rate of the quark-gluon plasma around the critical temperature.

PMID- 29350950
TI  - Local Melting Attracts Grain Boundaries in Colloidal Polycrystals.
AB  - We find that laser-induced local melting attracts and deforms grain boundaries in
      2D colloidal crystals. When a melted region in contact with the edge of a crystal
      grain recrystallizes, it deforms the grain boundary-this attraction is driven by
      the multiplicity of deformed grain boundary configurations. Furthermore, the
      attraction provides a method to fabricate artificial colloidal crystal grains of
      arbitrary shape, enabling new experimental studies of grain boundary dynamics and
      ultimately hinting at a novel approach for fabricating materials with designer
      microstructures.

PMID- 29350951
TI  - High-Fidelity Preservation of Quantum Information During Trapped-Ion Transport.
AB  - A promising scheme for building scalable quantum simulators and computers is the
      synthesis of a scalable system using interconnected subsystems. A prerequisite
      for this approach is the ability to faithfully transfer quantum information
      between subsystems. With trapped atomic ions, this can be realized by
      transporting ions with quantum information encoded into their internal states.
      Here, we measure with high precision the fidelity of quantum information encoded
      into hyperfine states of a ^{171}Yb^{+} ion during ion transport in a
      microstructured Paul trap. Ramsey spectroscopy of the ion's internal state is
      interleaved with up to 4000 transport operations over a distance of 280  MUm each
      taking 12.8  MUs. We obtain a state fidelity of 99.9994( _{-7}^{+6})% per ion
      transport.

PMID- 29350952
TI  - Fast Data Sorting with Modified Principal Component Analysis to Distinguish
      Unique Single Molecular Break Junction Trajectories.
AB  - A simple and fast analysis method to sort large data sets into groups with shared
      distinguishing characteristics is described and applied to single molecular break
      junction conductance versus electrode displacement data. The method, based on
      principal component analysis, successfully sorts data sets based on the
      projection of the data onto the first or second principal component of the
      correlation matrix without the need to assert any specific hypothesis about the
      expected features within the data. This is an improvement on the current
      correlation matrix analysis approach because it sorts data automatically, making
      it more objective and less time consuming, and our method is applicable to a wide
      range of multivariate data sets. Here the method is demonstrated on two systems.
      First, it is demonstrated on mixtures of two molecules with identical anchor
      groups and similar lengths, but either a pi (high conductance) or a sigma (low
      conductance) bridge. The mixed data are automatically sorted into two groups
      containing one molecule or the other. Second, it is demonstrated on break
      junction data measured with the pi bridged molecule alone. Again, the method
      distinguishes between two groups. These groups are tentatively assigned to
      different geometries of the molecule in the junction.

PMID- 29350953
TI  - Charged Polaron Polaritons in an Organic Semiconductor Microcavity.
AB  - We report strong coupling between light and polaron optical excitations in a
      doped organic semiconductor microcavity at room temperature. Codepositing MoO_{3}
      and the hole transport material 4, 4^{'}-cyclohexylidenebis[N, N-bis(4
      methylphenyl)benzenamine] introduces a large hole density with a narrow linewidth
      optical transition centered at 1.8 eV and an absorption coefficient exceeding
      10^{4}  cm^{-1}. Coupling this transition to a Fabry-Perot cavity mode yields
      upper and lower polaron polariton branches that are clearly resolved in angle
      dependent reflectivity with a vacuum Rabi splitting hOmega_{R}>0.3  eV. This
      result establishes a path to electrically control polaritons in organic
      semiconductors and may lead to increased polariton-polariton Coulombic
      interactions that lower the threshold for nonlinear phenomena such as polariton
      condensation and lasing.

PMID- 29350954
TI  - Invariance of Topological Indices Under Hilbert Space Truncation.
AB  - We show that the topological index of a wave function, computed in the space of
      twisted boundary phases, is preserved under Hilbert space truncation, provided
      the truncated state remains normalizable. If truncation affects the boundary
      condition of the resulting state, the invariant index may acquire a different
      physical interpretation. If the index is symmetry protected, the truncation
      should preserve the protecting symmetry. We discuss implications of this
      invariance using paradigmatic integer and fractional Chern insulators, Z_{2}
      topological insulators, and spin-1 Affleck-Kennedy-Lieb-Tasaki and Heisenberg
      chains, as well as its relation with the notion of bulk entanglement. As a
      possible application, we propose a partial quantum tomography scheme from which
      the topological index of a generic multicomponent wave function can be extracted
      by measuring only a small subset of wave function components, equivalent to the
      measurement of a bulk entanglement topological index.

PMID- 29350955
TI  - Rate Dependence of Elementary Rearrangements and Spatiotemporal Correlations in
      the 3D Flow of Soft Solids.
AB  - We use a combination of confocal microscopy, rheology, and molecular dynamics
      simulations to investigate jammed emulsions under shear, by analyzing the 3D
      droplets rearrangements in the shear frame. Our quantitative analysis of local
      dynamics reveals elementary nonaffine rearrangements that underlie the onset of
      the flow at small strains. We find that the mechanism of unjamming and the upturn
      in the material flow curve are associated to a qualitative change in
      spatiotemporal correlations of such rearrangements with the applied shear rate.
      At high shear rates, droplet clusters follow coordinated, stringlike motion.
      Conversely, at low shear rates, the elementary nonaffine rearrangements exhibit
      longer-ranged correlations, with complex spatiotemporal patterns. The 3D
      microscopic details provide novel insights into the specific features of the
      material flow curve, common to a large class of technologically relevant soft
      disordered solids and new fundamental ingredients for constitutive models.

PMID- 29350956
TI  - Negative-Mass Instability of the Spin and Motion of an Atomic Gas Driven by
      Optical Cavity Backaction.
AB  - We realize a spin-orbit interaction between the collective spin precession and
      center-of-mass motion of a trapped ultracold atomic gas, mediated by spin- and
      position-dependent dispersive coupling to a driven optical cavity. The collective
      spin, precessing near its highest-energy state in an applied magnetic field, can
      be approximated as a negative-mass harmonic oscillator. When the Larmor
      precession and mechanical motion are nearly resonant, cavity mediated coupling
      leads to a negative-mass instability, driving exponential growth of a correlated
      mode of the hybrid system. We observe this growth imprinted on modulations of the
      cavity field and estimate the full covariance of the resulting two-mode state by
      observing its transient decay during subsequent free evolution.

PMID- 29350957
TI  - Relativistic Fluid Dynamics Far From Local Equilibrium.
AB  - Fluid dynamics is traditionally thought to apply only to systems near local
      equilibrium. In this case, the effective theory of fluid dynamics can be
      constructed as a gradient series. Recent applications of resurgence suggest that
      this gradient series diverges, but can be Borel resummed, giving rise to a
      hydrodynamic attractor solution which is well defined even for large gradients.
      Arbitrary initial data quickly approaches this attractor via nonhydrodynamic mode
      decay. This suggests the existence of a new theory of far-from-equilibrium fluid
      dynamics. In this Letter, the framework of fluid dynamics far from local
      equilibrium for a conformal system is introduced, and the hydrodynamic attractor
      solutions for resummed Baier-Romatschke-Son-Starinets-Stephanov theory, kinetic
      theory in the relaxation time approximation, and strongly coupled N=4 super Yang
      Mills theory are identified for a system undergoing Bjorken flow.

PMID- 29350958
TI  - Double-Weyl Phonons in Transition-Metal Monosilicides.
AB  - We employed ab initio calculations to identify a class of crystalline materials
      of MSi (M=Fe, Co, Mn, Re, Ru) having double-Weyl points in both their acoustic
      and optical phonon spectra. They exhibit novel topological points termed "spin-1
      Weyl point" at the Brillouin zone center and "charge-2 Dirac point" at the zone
      corner. The corresponding gapless surface phonon dispersions are two helicoidal
      sheets whose isofrequency contours form a single noncontractible loop in the
      surface Brillouin zone. In addition, the global structure of the surface bands
      can be analytically expressed as double-periodic Weierstrass elliptic functions.

PMID- 29350959
TI  - Under-the-Tunneling-Barrier Recollisions in Strong-Field Ionization.
AB  - A new pathway of strong-laser-field-induced ionization of an atom is identified
      which is based on recollisions under the tunneling barrier. With an amended
      strong-field approximation, the interference of the direct and the under-the
      barrier recolliding quantum orbits are shown to induce a measurable shift of the
      peak of the photoelectron momentum distribution. The scaling of the momentum
      shift is derived relating the momentum shift to the tunneling delay time
      according to the Wigner concept. This allows us to extend the Wigner concept for
      the quasistatic tunneling time delay into the nonadiabatic domain. The obtained
      corrections to photoelectron momentum distributions are also relevant for state
      of-the-art accuracy of strong-field photoelectron spectrograms in general.

PMID- 29350960
TI  - Enhanced Electromagnetic Corrections to the Rare Decay B_{s,d}->MU^{+}MU^{-}.
AB  - We investigate electromagnetic corrections to the rare B-meson leptonic decay
      B_{s,d}->MU^{+}MU^{-} from scales below the bottom-quark mass m_{b}. Contrary to
      QCD effects, which are entirely contained in the B-meson decay constant, we find
      that virtual photon exchange can probe the B-meson structure, resulting in a
      "nonlocal annihilation" effect. We find that this effect gives rise to a
      dynamical enhancement by a power of m_{b}/Lambda_{QCD} and by large logarithms.
      The impact of this novel effect on the branching ratio of B_{s,d}->MU^{+}MU^{-}
      is about 1%, of the order of the previously estimated nonparametric theoretical
      uncertainty, and four times the size of previous estimates of next-to-leading
      order QED effects due to residual scale dependence. We update the standard model
      (SM) prediction to B[over -](B_{s}->MU^{+}MU^{-})_{SM}=(3.57+/-0.17)*10^{-9}.

PMID- 29350961
TI  - Electron Correlation from the Adiabatic Connection for Multireference Wave
      Functions.
AB  - An adiabatic connection (AC) formula for the electron correlation energy is
      derived for a broad class of multireference wave functions. The AC expression
      recovers dynamic correlation energy and assures a balanced treatment of the
      correlation energy. Coupling the AC formalism with the extended random phase
      approximation allows one to find the correlation energy only from reference one-
      and two-electron reduced density matrices. If the generalized valence bond
      perfect pairing model is employed a simple closed-form expression for the
      approximate AC formula is obtained. This results in the overall M^{5} scaling of
      the computation cost making the method one of the most efficient multireference
      approaches accounting for dynamic electron correlation also for the strongly
      correlated systems.

PMID- 29350963
TI  - Observation of the Quantum Hall Effect in Confined Films of the Three-Dimensional
      Dirac Semimetal Cd_{3}As_{2}.
AB  - The magnetotransport properties of epitaxial films of Cd_{3}As_{2}, a paradigm
      three-dimensional Dirac semimetal, are investigated. We show that an energy gap
      opens in the bulk electronic states of sufficiently thin films and, at low
      temperatures, carriers residing in surface states dominate the electrical
      transport. The carriers in these states are sufficiently mobile to give rise to a
      quantized Hall effect. The sharp quantization demonstrates surface transport that
      is virtually free of parasitic bulk conduction and paves the way for novel
      quantum transport studies in this class of topological materials. Our results
      also demonstrate that heterostructuring approaches can be used to study and
      engineer quantum states in topological semimetals.

PMID- 29350962
TI  - High-Speed Device-Independent Quantum Random Number Generation without a
      Detection Loophole.
AB  - Quantum mechanics provides the means of generating genuine randomness that is
      impossible with deterministic classical processes. Remarkably, the
      unpredictability of randomness can be certified in a manner that is independent
      of implementation devices. Here, we present an experimental study of device
      independent quantum random number generation based on a detection-loophole-free
      Bell test with entangled photons. In the randomness analysis, without the
      independent identical distribution assumption, we consider the worst case
      scenario that the adversary launches the most powerful attacks against the
      quantum adversary. After considering statistical fluctuations and applying an 80 
      Gb*45.6  Mb Toeplitz matrix hashing, we achieve a final random bit rate of 114 
      bits/s, with a failure probability less than 10^{-5}. This marks a critical step
      towards realistic applications in cryptography and fundamental physics tests.

PMID- 29350964
TI  - Generation of High-Power High-Intensity Short X-Ray Free-Electron-Laser Pulses.
AB  - X-ray free-electron lasers combine a high pulse power, short pulse length, narrow
      bandwidth, and high degree of transverse coherence. Any increase in the photon
      pulse power, while shortening the pulse length, will further push the frontier on
      several key x-ray free-electron laser applications including single-molecule
      imaging and novel nonlinear x-ray methods. This Letter shows experimental results
      at the Linac Coherent Light Source raising its maximum power to more than 300% of
      the current limit while reducing the photon pulse length to 10 fs. This was
      achieved by minimizing residual transverse-longitudinal centroid beam offsets and
      beam yaw and by correcting the dispersion when operating over 6 kA peak current
      with a longitudinally shaped beam.

PMID- 29350965
TI  - Publisher's Note: Enhancing Coherent Light-Matter Interactions through
      Microcavity-Engineered Plasmonic Resonances [Phys. Rev. Lett. 119, 233901
      (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.233901.

PMID- 29350966
TI  - Improved Limits on Axionlike-Particle-Mediated P, T-Violating Interactions
      between Electrons and Nucleons from Electric Dipole Moments of Atoms and
      Molecules.
AB  - In the presence of P, T-violating interactions, the exchange of axionlike
      particles between electrons and nucleons in atoms and molecules induces electric
      dipole moments (EDMs) of atoms and molecules. We perform calculations of such
      axion-exchange-induced atomic EDMs using the relativistic Hartree-Fock-Dirac
      method including electron core polarization corrections. We present analytical
      estimates to explain the dependence of these induced atomic EDMs on the axion
      mass and atomic parameters. From the experimental bounds on the EDMs of atoms and
      molecules, including ^{133}Cs, ^{205}Tl, ^{129}Xe, ^{199}Hg, ^{171}Yb^{19}F,
      ^{180}Hf^{19}F^{+}, and ^{232}Th^{16}O, we constrain the P, T-violating scalar
      pseudoscalar nucleon-electron and electron-electron interactions mediated by a
      generic axionlike particle of arbitrary mass. Our limits improve on existing
      laboratory bounds from other experiments by many orders of magnitude for
      m_{a}?10^{-2}  eV. We also place constraints on CP violation in certain types of
      relaxion models.

PMID- 29350967
TI  - Chiral Topological Superconductors Enhanced by Long-Range Interactions.
AB  - We study the phase diagram and edge states of a two-dimensional p-wave
      superconductor with long-range hopping and pairing amplitudes. New topological
      phases and quasiparticles different from the usual short-range model are
      obtained. When both hopping and pairing terms decay with the same exponent, one
      of the topological chiral phases with propagating Majorana edge states gets
      significantly enhanced by long-range couplings. On the other hand, when the long
      range pairing amplitude decays more slowly than the hopping, we discover new
      topological phases where propagating Majorana fermions at each edge pair
      nonlocally and become gapped even in the thermodynamic limit. Remarkably, these
      nonlocal edge states are still robust, remain separated from the bulk, and are
      localized at both edges at the same time. The inclusion of long-range effects is
      potentially applicable to recent experiments with magnetic impurities and islands
      in 2D superconductors.

PMID- 29350968
TI  - Spin Switching via Quantum Dot Spin Valves.
AB  - We develop a theory for spin transport and magnetization dynamics in a quantum
      dot spin valve, i.e., two magnetic reservoirs coupled to a quantum dot. Our
      theory is able to take into account effects of strong correlations. We
      demonstrate that, as a result of these strong correlations, the dot gate voltage
      enables control over the current-induced torques on the magnets and, in
      particular, enables voltage-controlled magnetic switching. The electrical
      resistance of the structure can be used to read out the magnetic state. Our model
      may be realized by a number of experimental systems, including magnetic scanning
      tunneling microscope tips and artificial quantum dot systems.

PMID- 29350969
TI  - Noise of a Chargeless Fermi Liquid.
AB  - We construct a Fermi liquid theory to describe transport in a superconductor
      quantum dot-normal metal junction close to the singlet-doublet (parity changing)
      transition of the dot. Though quasiparticles do not have a definite charge in
      this chargeless Fermi liquid, in the case of particle-hole symmetry, a mapping to
      the Anderson model unveils a hidden U(1) symmetry and a corresponding
      pseudocharge. In contrast to other correlated Fermi liquids, the back scattering
      noise reveals an effective charge equal to the charge of Cooper pairs, e^{*}=2e.
      In addition, we find a strong suppression of noise when the linear conductance is
      unitary, even for its nonlinear part.

PMID- 29350970
TI  - Exact Boson-Fermion Duality on a 3D Euclidean Lattice.
AB  - The idea of statistical transmutation plays a crucial role in descriptions of the
      fractional quantum Hall effect. However, a recently conjectured duality between a
      critical boson and a massless two-component Dirac fermion extends this notion to
      gapless systems. This duality sheds light on highly nontrivial problems such as
      the half-filled Landau level, the superconductor-insulator transition, and
      surface states of strongly coupled topological insulators. Although this boson
      fermion duality has undergone many consistency checks, it has remained unproven.
      We describe the duality in a nonperturbative fashion using an exact UV mapping of
      partition functions on a 3D Euclidean lattice.

PMID- 29350971
TI  - Rating Nasolabial Aesthetics in Unilateral Cleft Lip and Palate Patients: Cropped
      Versus Full-Face Images.
AB  - OBJECTIVE: To determine if cropping facial images affects nasolabial aesthetics
      assessments in unilateral cleft lip patients and to evaluate the effect of facial
      attractiveness on nasolabial evaluation. DESIGN: Two cleft surgeons and one cleft
      orthodontist assessed standardized frontal photographs 4 times; nasolabial
      aesthetics were rated on cropped and full-face images using the Cleft Aesthetic
      Rating Scale, and total facial attractiveness was rated on full-face images with
      and without the nasolabial area blurred using a 5-point Likert scale. SETTING:
      Cleft Palate Craniofacial Unit of a University Medical Center. PATIENTS:
      Inclusion criteria: nonsyndromic unilateral cleft lip and an available frontal
      view photograph around 10 years of age. EXCLUSION CRITERIA: a history of facial
      trauma and an incomplete cleft. Eighty-one photographs were available for
      assessment. MAIN OUTCOME MEASURES: Differences in mean CARS scores between
      cropped versus full-face photographs and attractive versus unattractive rated
      patients were evaluated by paired t test. RESULTS: Nasolabial aesthetics are
      scored more negatively on full-face photographs compared to cropped photographs,
      regardless of facial attractiveness. (Mean CARS score, nose: cropped = 2.8, full
      face = 3.0, P < .001; lip: cropped = 2.4, full-face = 2.7, P < .001; nose and
      lip: cropped = 2.6, full-face = 2.8, P < .001). CONCLUSION: Aesthetic outcomes of
      the nasolabial area are assessed significantly more positively when using cropped
      images compared to full-face images. For this reason, cropping images, revealing
      the nasolabial area only, is recommended for aesthetical assessments.

PMID- 29350972
TI  - Extracorporeal Life Support in Immunocompromised Patients with Severe Acute
      Respiratory Distress Syndrome. Decide Wisely, Early, and in a Personalized Way.

PMID- 29350973
TI  - Epithelial Progenitor Cells Take Center Stage in Lung Transplantation.

PMID- 29350974
TI  - Use of Simulation-Based Training to Aid in Implementing Complex Health
      Technology.
AB  - Clinicians are adult learners in a complex environment that historically does not
      invest in training in a way that is conducive to these types of learners. Adult
      learners are independent, self-directed, and goal oriented. In today's fast-paced
      clinical setting, a practical need exists for nurses and clinicians to master the
      technology they use on a daily basis, especially as medical devices have become
      more interconnected and complex. As hospitals look to embrace new technologies,
      medical device companies must provide clinical end-user training. This should be
      a required part of the selection process when considering the purchase of any
      complex medical technology. However, training busy clinicians in a traditional
      classroom setting can be difficult and costly. A simple, less expensive solution
      is online simulation training. This interactive training provides a virtual,
      "hands-on" end-user experience in advance of implementing new equipment. Online
      simulation training ensures knowledge retention and comprehension and, most
      importantly, that the training leads to end-user satisfaction and the ability to
      confidently operate new equipment. A review of the literature revealed that
      online simulation, coupled with the use of adult learning principles and
      experiential learning, may enhance the experience of clinical end users.

PMID- 29350975
TI  - Master the Fundamentals Before Getting Creative and Fancy.

PMID- 29350976
TI  - Ten Questions With ....

PMID- 29350978
TI  - Nurses Underscore Value of Collaboration when Implementing Health Technology.

PMID- 29350979
TI  - Dispelling Confusion Among Various Electrosurgery Technologies.

PMID- 29350980
TI  - Taking the Temperature of Clinical Technology Efficiency.

PMID- 29350981
TI  - ST91 Working Group Strives toward More Stringent Guidelines for Processing
      Endoscopes.

PMID- 29350982
TI  - 'Everyone in Healthcare Is a Risk Manager': Achieving Risk-Savvy Cultures.

PMID- 29350983
TI  - CTO Foresees Future of CMMS-Enabled 'True Interoperability'.

PMID- 29350984
TI  - Conquering the Complexity of Sterilization Instructions for Use.

PMID- 29350985
TI  - Collaboration Fuels Success of Infusion Management Interoperability Initiative.

PMID- 29350986
TI  - Overcoming User-Centered Challenges with Complex Health Technology.

PMID- 29350987
TI  - Wonder Women: A New Type of Healthcare Technology Professional.

PMID- 29350988
TI  - Thing Two and Thing One.

PMID- 29350992
TI  - Using Data to Influence Choice.

PMID- 29350993
TI  - Frontlines: Captivated by the Career.

PMID- 29350995
TI  - A Review of Analytical Methods for the determination of Clopidogrel in
      Pharmaceuticals and Biological Matrices.
AB  - P2Y12 belongs to a group of G protein-coupled (GPCR) purinergic receptors and is
      a receptor for adenosine diphosphate (ADP). The P2Y12 receptor is involved in
      platelet aggregation and acts as a biological target for treating
      thromboembolisms and other clotting disorders. The use of Clopidogrel (CLO) has
      improved the morbidity and mortality endpoints including cardiovascular death,
      recurrent myocardial infarction (MI) and stroke at 30 days after percutaneous
      coronary intervention (PCI). CLO is one such drug that specifically and
      irreversibly inhibits the P2Y12 subtype of ADP receptor. This review delivers a
      detail description of various analytical methods published for the estimation of
      CLO and its combinations in pharmaceuticals and biological matrices. The review
      highlights the basic as well as advanced techniques performed for estimating CLO.
      The most commonly used assay techniques were UV and Visible spectrophotometry,
      high performance liquid chromatography (HPLC), high performance thin layer
      chromatography (HPTLC), micellar liquid chromatography (MLC), micellar electro
      kinetic chromatography (MEKC) and liquid chromatography-tandem mass spectrometry
      (LC-MS/MS). Despite other analytical methods employed for the assay of CLO, the
      review reveals that the technique of HPLC with UV detection was widely used.

PMID- 29350996
TI  - Conduct Disorder and Neighborhood Effects.
AB  - There has been a considerable amount of scholarly attention to the relationship
      between neighborhood effects and conduct disorder, particularly in recent years.
      Having said this, it has been nearly two decades since a comprehensive synthesis
      of this literature has been conducted. Relying on a detailed and comprehensive
      search strategy and inclusion criteria, this article offers a systematic and
      interdisciplinary review of 47 empirical studies that have examined neighborhood
      effects and conduct disorder. Described results suggest that there are generally
      robust linkages between adverse neighborhood factors and conduct disorder and
      externalizing behavior problems, as 67 of the 93 (72.04%) effect sizes derived
      from these studies yielded statistically significant neighborhood effects. The
      review also identifies salient mediating and moderating influences. It discusses
      study limitations and directions for future research as well.

PMID- 29350997
TI  - Realizing the Mass Public Benefit of Evidence-Based Psychological Therapies: The
      IAPT Program.
AB  - Empirically supported psychological therapies have been developed for many mental
      health conditions. However, in most countries only a small proportion of the
      public benefit from these advances. The English Improving Access to Psychological
      Therapies (IAPT) program aims to bridge the gap between research and practice by
      training over 10,500 new psychological therapists in empirically supported
      treatments and deploying them in new services for the treatment of depression and
      anxiety disorders. Currently IAPT treats over 560,000 patients per year, obtains
      clinical outcome data on 98.5% of these individuals, and places this information
      in the public domain. Around 50% of patients treated in IAPT services recover,
      and two-thirds show worthwhile benefits. The clinical and economic arguments on
      which IAPT is based are presented, along with details of the service model, how
      the program was implemented, and recent findings about service organization.
      Limitations and future directions are outlined.

PMID- 29351000
TI  - Age Effects on Cerebral Oxygenation and Behavior in Children with Sleep
      disordered Breathing.
AB  - RATIONALE: Childhood sleep-disordered breathing ranges in severity from primary
      snoring to obstructive sleep apnea and is associated with behavioral and
      neurocognitive deficits. It remains unknown why children with primary snoring,
      who do not experience peripheral oxygen desaturation or sleep fragmentation,
      experience similar daytime deficits as those with obstructive sleep apnea or why
      effects are age-dependent. OBJECTIVES: To examine cerebral tissue oxygenation and
      oxygen extraction as an explanation for daytime deficits in children with primary
      snoring. METHODS: Children referred for suspected sleep-disordered breathing and
      nonsnoring control subjects underwent overnight polysomnography with near
      infrared spectroscopy. Children were categorized into 3- to 6-year (n = 87) and 7
      to 12-year (n = 72) old groups, and according to the obstructive apnea-hypopnea
      index into primary snoring (<=1 event/h), mild (>1-5 events/h), and
      moderate/severe obstructive sleep apnea (>5 events/h). Cognitive and behavioral
      performance were assessed. MEASUREMENTS AND MAIN RESULTS: In the 3- to 6-year
      group, there were no differences in cerebral oxygenation or oxygen extraction
      between severity groups. In the 7- to 12-year group, cerebral oxygenation was
      significantly lower, although these differences were small, in control subjects
      versus primary snoring during quiet wakefulness before sleep onset, N1, and REM.
      Oxygen extraction was significantly higher in control subjects versus primary
      snoring during N1 sleep, with no differences between primary snoring and
      obstructive sleep apnea groups. Cerebral oxygenation was not associated with
      cognitive performance in either age group or behavior in the 3- to 6-year group;
      however, it was associated with behavior in the school-aged children.
      CONCLUSIONS: Children with sleep-disordered breathing are able to maintain
      cerebral oxygenation, and the small changes observed are not related to cognitive
      deficits. However, in older children these differences were related to behavioral
      measures.

PMID- 29350998
TI  - Overexpression of the neuronal human (pro)renin receptor mediates angiotensin II
      independent blood pressure regulation in the central nervous system.
AB  - Despite advances in antihypertensive therapeutics, at least 15-20% of
      hypertensive patients have resistant hypertension through mechanisms that remain
      poorly understood. In this study, we provide a new mechanism for the regulation
      of blood pressure (BP) in the central nervous system (CNS) by the (pro)renin
      receptor (PRR), a recently identified component of the renin-angiotensin system
      that mediates ANG II formation in the CNS. Although PRR also mediates ANG II
      independent signaling, the importance of these pathways in BP regulation is
      unknown. Here, we developed a unique transgenic mouse model overexpressing human
      PRR (hPRR) specifically in neurons (Syn-hPRR). Intracerebroventricular infusion
      of human prorenin caused increased BP in Syn-hPRR mice. This BP response was
      attenuated by a NADPH oxidase (NOX) inhibitor but not by antihypertensive agents
      that target the renin-angiotensin system. Using a brain-targeted genetic
      knockdown approach, we found that NOX4 was the key isoform responsible for the
      prorenin-induced elevation of BP in Syn-hPRR mice. Moreover, inhibition of ERK
      significantly attenuated the increase in NOX activity and BP induced by human
      prorenin. Collectively, our findings indicate that an ANG II-independent, PRR
      mediated signaling pathway regulates BP in the CNS by a PRR-ERK-NOX4 mechanism.
      NEW & NOTEWORTHY This study characterizes a new transgenic mouse model with
      overexpression of the human (pro)renin receptor in neurons and demonstrated a
      novel angiotensin II-independent mechanism mediated by human prorenin and the
      (pro)renin receptor in the central regulation of blood pressure.

PMID- 29351001
TI  - Precision Medicine in Asthma: Integrating Imaging and Inflammatory Biomarkers.

PMID- 29351002
TI  - Protective effect of the standardized leaf extract of Ginkgo biloba (EGb761)
      against hypertension-induced renal injury in rats.
AB  - BACKGROUND: Ginkgo biloba leaves extract has been widely used worldwide to
      protect against oxidative stress-induced cell damage and improves blood
      circulation. METHODS: The potential protective role of the standardized leaf
      extract of Ginkgo biloba (EGb761) on hypertension-induced renal injury was
      investigated in rats. Hypertension was induced in rats by L-NAME. RESULT:
      Repeated treatment with EGb761 produced progressive reductions in the systolic,
      diastolic and mean arterial blood pressure. Also, EGb761 increased the
      progressive reductions in blood pressure induced by losartan. Hypertension
      induced marked elevation of renal malondialdehyde (MDA) and nitrite levels and
      reduction of reduced glutathione (GSH) level were inhibited by EGb761. In
      addition, hypertension-induced increases in tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta)) levels in renal
      tissues were inhibited by EGb761. Also, treatment with EGb761 inhibited
      hypertension-induced decrease in endothelial nitric oxide synthase (eNOS) protein
      expression and increase in the protein expressions of inducible NO synthase
      (iNOS), TNF-alpha, IL-6 and IL-1B in the kidney tissues. EGb761 enhanced losartan
      effects on renal tissues oxidative stress, nitrite, and inflammatory markers
      levels and on protein expressions of eNOS, iNOS, TNF-alpha, IL-6 and IL-1B.
      effects. CONCLUSIONS: These results indicate that EGb761 has the ability to
      protect against hypertension-induced renal injury.

PMID- 29351003
TI  - The Yin and Yang of endothelium-derived vasodilator factors.

PMID- 29350999
TI  - Sex differences in abdominal aortic aneurysms.
AB  - Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality
      rate in the instance of rupture. AAA is a multifactorial disease, and the
      etiology is still not fully understood. AAA is more likely to occur in men, but
      women have a greater risk of rupture and worse prognosis. Women are reportedly
      protected against AAA possibly by premenopausal levels of estrogen and are, on
      average, diagnosed at older ages than men. Here, we review the present body of
      research on AAA pathophysiology in humans, animal models, and cultured cells,
      with an emphasis on sex differences and sex steroid hormone signaling.

PMID- 29351004
TI  - Duchenne muscular dystrophy: an updated review of common available therapies.
AB  - BACKGROUND AND PURPOSE: Duchenne muscular dystrophy (DMD) is a lethal progressive
      pediatric muscle disorder and genetically inherited as an X-linked disease that
      caused by mutations in the dystrophin gene. DMD leads to progressive muscle
      weakness, degeneration, and wasting; finally, follows with the premature demise
      in affected individuals due to respiratory and/or cardiac failure typically by
      age of 30. For decades, scientists tried massively to find an effective therapy
      method, but there is no absolute cure currently for patients with DMD,
      nevertheless, recent advanced progressions on the treatment of DMD will be
      hopeful in the future. Several promising gene therapies are currently under
      investigation. These include gene replacement, exon skipping, suppression of stop
      codons. More recently, a promising gene editing tool referred to as CRISPR/Cas9
      offers exciting perspectives for restoring dystrophin expression in patients with
      DMD. This review intents to briefly describe these methods and comment on their
      advances. Since DMD is a genetic disorder, it should be treated by replacing the
      deficient DMD copy with a functional one. However, there are different types of
      mutations in this gene, so such therapeutic approaches are highly mutation
      specific and thus are personalized. Therefore, DMD has arisen as a model of
      genetic disorder for understanding and overcoming of the challenges of developing
      personalized genetic medicines, consequently, the lessons learned from these
      approaches will be applicable to many other disorders. CONCLUSIONS: This review
      provides an update on the recent gene therapies for DMD that aim to compensate
      for dystrophin deficiency and the related clinical trials.

PMID- 29351005
TI  - An integrated operational definition and conceptual model of asthma self
      management in teens.
AB  - OBJECTIVES: A previous definition of adolescent asthma self-management was
      derived from interviews with clinicians/researchers and published literature;
      however, it did not incorporate perspectives of teens or parents. Therefore, we
      conducted in-depth interviews with teens and parents and synthesized present
      findings with the prior analysis to develop a more encompassing definition and
      model. METHODS: Focal concepts were qualitatively extracted from 14-day self
      management voice-diaries (n = 14) and 1-hour interviews (n = 42) with teens and
      parents (28 individuals) along with concepts found in the previous
      clinical/research oriented analysis. Conceptual structure and relationships were
      identified and key findings synthesized to develop a revised definition and model
      of adolescent asthma self-management. RESULTS: There were two primary self
      management constructs: processes of self-management and tasks of self-management.
      Self-management was defined as the iterative process of assessing, deciding, and
      responding to specific situations in order to achieve personally important
      outcomes. Clinically relevant asthma self-management tasks included monitoring
      asthma, managing active issues through pharmacologic and non-pharmacologic
      strategies, preventing future issues, and communicating with others as needed.
      Self-management processes were reciprocally influenced by intrapersonal factors
      (both cognitive and physical), interpersonal factors (family, social and physical
      environments), and personally relevant asthma and non-asthma outcomes.
      CONCLUSION: This is the first definition of asthma self-management incorporating
      teen, parent, clinician, and researcher perspectives, which suggests that self
      management processes and behaviors are influenced by individually variable
      personal and interpersonal factors, and are driven by personally important
      outcomes. Clinicians and researchers should investigate teens' symptom
      perceptions, medication beliefs, current approaches to symptom management,
      relevant outcomes, and personal priorities.

PMID- 29351006
TI  - Associations between microalbuminuria and parameters of flow-mediated
      vasodilatation obtained by continuous measurement approaches.
AB  - The associations between microalbuminuria and various parameters of flow-mediated
      vasodilatation (FMD) are not completely understood. We retrospectively analyzed
      265 consecutive patients who underwent coronary angiography and in whom we could
      measure FMD and the urine albumin-creatinine ratio (UACR). Using 15 continuous
      measurement approaches, we measured FMD as the magnitude of the percentage change
      in the brachial artery diameter from baseline to peak (bFMD), the maximum FMD
      rate calculated as the maximal slope of dilation (FMD-MDR), and the integrated
      FMD response calculated as the area under the dilation curve during the 60- and
      120-s dilation periods (FMD-AUC60 and FMD-AUC120). We divided the patients into
      two groups according to UACR: normoalbuminuria (NOR, n = 211) and
      microalbuminuria (MIC, n = 54). The MIC group showed a significantly higher
      percentage of coronary artery disease than the NOR group. FMD-AUC60 and FMD
      AUC120, but not FMD-MDR, in the MIC group were significantly lower than those in
      the NOR group. On the other hand, bFMD in the MIC group tended to be lower than
      that in the NOR group, but this difference was not significant. A multiple
      regression analysis indicated that FMD-AUC120 and diabetes mellitus were
      predictors of MIC. Finally, we defined the cut-off value of FMD-AUC120 for the
      presence of MIC in all patients as 8.4 mm x second (sensitivity 0.640,
      specificity 0.588) by a receiver-operating characteristic curve analysis. In
      conclusion, this study provides more definitive evidence for the association of
      microalbuminuria with endothelial dysfunction. FMD-AUC120 may be a superior
      marker for MIC.

PMID- 29351007
TI  - Timing of Renal Support and Outcome of Septic Shock and Acute Respiratory
      Distress Syndrome. A Post Hoc Analysis of the AKIKI Randomized Clinical Trial.
AB  - RATIONALE: The optimal strategy for initiation of renal replacement therapy (RRT)
      in patients with severe acute kidney injury in the context of septic shock and
      acute respiratory distress syndrome (ARDS) is unknown. OBJECTIVES: To examine the
      effect of an early compared with a delayed RRT initiation strategy on 60-day
      mortality according to baseline sepsis status, ARDS status, and severity.
      METHODS: Post hoc analysis of the AKIKI (Artificial Kidney Initiation in Kidney
      Injury) trial. MEASUREMENTS AND MAIN RESULTS: Subgroups were defined according to
      baseline characteristics: sepsis status (Sepsis-3 definition), ARDS status
      (Berlin definition), Simplified Acute Physiology Score 3 (SAPS 3), and Sepsis
      related Organ Failure Assessment (SOFA). Of 619 patients, 348 (56%) had septic
      shock and 207 (33%) had ARDS. We found no significant influence of the baseline
      sepsis status (P = 0.28), baseline ARDS status (P = 0.94), and baseline severity
      scores (P = 0.77 and P = 0.46 for SAPS 3 and SOFA, respectively) on the
      comparison of 60-day mortality according to RRT initiation strategy. A delayed
      RRT initiation strategy allowed 45% of patients with septic shock and 46% of
      patients with ARDS to escape RRT. Urine output was higher in the delayed group.
      Renal function recovery occurred earlier with the delayed RRT strategy in
      patients with septic shock or ARDS (P < 0.001 and P = 0.003, respectively). Time
      to successful extubation in patients with ARDS was not affected by RRT strategy
      (P = 0.43). CONCLUSIONS: Early RRT initiation strategy was not associated with
      any improvement of 60-day mortality in patients with severe acute kidney injury
      and septic shock or ARDS. Unnecessary and potentially risky procedures might
      often be avoided in these fragile populations. Clinical trial registered with
      www.clinicaltrials.gov (NCT 01932190).

PMID- 29351008
TI  - Delay to Colectomy and Survival for Patients Diagnosed with Colon Cancer.
AB  - BACKGROUND: A long wait-time for colectomy for colon cancer should theoretically
      affect survival but, to date, the association between delay to colectomy and
      survival remains unresolved. METHODS: We studied 4,685 patients who underwent a
      colectomy for colon cancer between 1990 and 2012. Wait-time was defined as the
      number of days between diagnosis and colectomy. Cox regression models were used
      to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for
      all-cause mortality. RESULTS: The number of patients in the wait-time group of 1
      21 days was 3,529 (75.3%), 22-42 days was 842 (18.0%), 43-84 days was 253 (5.4%),
      and >84 days was 61 (1.3%). When compared to patients undergoing surgery in the
      first week after diagnosis, there was no increased risk of death until wait time
      >84 days (HR = 1.47; 95% CI, 1.02-2.11; p =.038). Patients in the wait time >84
      day group tended to be older, traveled further for colectomy, and had tumors with
      a lower histologic grade. CONCLUSIONS: Colectomy for colon cancer performed up to
      3 months following diagnosis is not associated with adverse long-term survival.
      These data provide a framework to address concerns over prolonged wait-times and
      direct efforts for timely surgery in patients with colon cancer.

PMID- 29351009
TI  - Life-History Traits Evolved Jointly with Climatic Niche and Disturbance Regime in
      the Genus Leucadendron (Proteaceae).
AB  - Organisms have evolved a diversity of life-history strategies to cope with
      variation in their environment. Persistence as adults and/or seeds across
      recruitment events allows species to dampen the effects of environmental
      fluctuations. The evolution of life cycles with overlapping generations should
      thus permit the colonization of environments with uncertain recruitment. We
      tested this hypothesis in Leucadendron (Proteaceae), a genus with high functional
      diversity native to fire-prone habitats in the South African fynbos. We analyzed
      the joint evolution of life-history traits (adult survival and seed-bank
      strategies) and ecological niches (climate and fire regime), using comparative
      methods and accounting for various sources of uncertainty. In the fynbos, species
      with canopy seed banks that are unable to survive fire as adults display
      nonoverlapping generations. In contrast, resprouters with an underground seed
      bank may be less threatened by extreme climatic events and fire intervals, given
      their iteroparity and long-lasting seed bank. Life cycles with nonoverlapping
      generations indeed jointly evolved with niches with less exposure to frost but
      not with those with less exposure to drought. Canopy seed banks jointly evolved
      with niches with more predictable fire return, compared to underground seed
      banks. The evolution of extraordinary functional diversity among fynbos plants
      thus reflects, at least in part, the diversity of both climates and fire regimes
      in this region.

PMID- 29351010
TI  - Using Human Vision to Detect Variation in Avian Coloration: How Bad Is It?
AB  - Assessing variation in animal coloration is difficult, as animals differ in their
      visual system properties. This has led some to propose that human vision can
      never be used to evaluate coloration, yet many studies have a long history of
      relying on human vision. To reconcile these views, we compared the reflectance
      spectra of preserved avian plumage elements with two measures that are human
      biased: RGB values from digital photographs and the corresponding reflectance
      spectra from a field guide. We measured 73 plumage elements across 14 bird
      species. The field guide reflectance spectra were drastically different from that
      of the actual birds, particularly for blue elements. However, principal component
      analyses on all three data sets indicated remarkably similar data structure. We
      conclude that human vision can detect much of the variation in coloration in the
      visible range, providing fodder for subsequent studies in ecology, evolution,
      behavior, and visual ecology.

PMID- 29351011
TI  - A Migratory Divide in the Painted Bunting (Passerina ciris).
AB  - In the painted bunting (Passerina ciris), a North American songbird, populations
      on the Atlantic coast and interior southern United States are known to be
      allopatric during the breeding season, but efforts to map connectivity with
      wintering ranges have been largely inconclusive. Using genomic and morphological
      data from museum specimens and banded birds, we found evidence of three
      genetically differentiated painted bunting populations with distinct wintering
      ranges and molt-migration phenologies. In addition to confirming that the
      Atlantic coast population remains allopatric throughout the annual cycle, we
      identified an unexpected migratory divide within the interior breeding range.
      Populations breeding in Louisiana winter on the Yucatan Peninsula and are
      parapatric with other interior populations that winter in mainland Mexico and
      Central America. Across the interior breeding range, genetic ancestry is also
      associated with variation in wing length, suggesting that selection may be
      promoting morphological divergence in populations with different migration
      strategies.

PMID- 29351012
TI  - Extreme Climate-Induced Life-History Plasticity in an Amphibian.
AB  - Age-specific survival and reproduction are closely linked to fitness and
      therefore subject to strong selection that typically limits their variability
      within species. Furthermore, adult survival rate in vertebrate populations is
      typically less variable over time than other life-history traits, such as
      fecundity or recruitment. Hence, adult survival is often conserved within a
      population over time, compared to the variation in survival found across taxa. In
      stark contrast to this general pattern, we report evidence of extreme short-term
      variation of adult survival in Rose's mountain toadlet (Capensibufo rosei), which
      is apparently climate induced. Over 7 years, annual survival rate varied between
      0.04 and 0.92, and 94% of this variation was explained by variation in breeding
      season rainfall. Preliminary results suggest that this variation reflects
      adaptive life-history plasticity to a degree thus far unrecorded for any
      vertebrate, rather than direct rainfall-induced mortality. In wet years, these
      toads appeared to achieve increased reproduction at the expense of their own
      survival, whereas in dry years, their survival increased at the expense of
      reproduction. Such environmentally induced plasticity may reflect a diversity of
      life-history strategies not previously appreciated among vertebrates.

PMID- 29351013
TI  - Leaf Form Evolution in Viburnum Parallels Variation within Individual Plants.
AB  - Few studies have critically evaluated how morphological variation within
      individual organisms corresponds to variation within and among species.
      Subindividual variation in plants facilitates such studies because their
      indeterminate modular growth generates multiple serially homologous structures
      along growing axes. Focusing on leaf form, we evaluate how subindividual trait
      variation relates to leaf evolution across Viburnum, a clade of woody
      angiosperms. In Viburnum we infer multiple independent origins of wide/lobed
      leaves with toothed margins from ancestors with elliptical, smooth-margined
      leaves. We document leaf variation along the branches of individual plants of 28
      species and among populations across the wide range of Viburnum dentatum. We
      conclude that when novel leaf forms evolved in Viburnum, they were intercalated
      at the beginning of the seasonal leaf sequence, which then generated a repeated
      spectrum of leaf forms along each branch (seasonal heteroblasty). We hypothesize
      that the existence of such a spectrum then facilitated additional evolutionary
      shifts, including reversions to more ancestral forms. We argue that the recurrent
      production of alternative phenotypes provides opportunities to canalize the
      production of particular forms and that this phenomenon has played an important
      role in generating macroscale patterns.

PMID- 29351014
TI  - Coinfection Timing Drives Host Population Dynamics through Changes in Virulence.
AB  - Infections of one host by multiple parasites are common, and several studies have
      found that the order of parasite invasion can affect both within-host competition
      and disease severity. However, it is unclear to what extent coinfection timing
      might be important to consider when modeling parasite impacts on host
      populations. Using a model system of two viruses infecting barley, we found that
      simultaneous infections of the two viruses were significantly more damaging to
      hosts than sequential coinfections. While priority effects were evident in within
      host concentrations of sequential coinfections, priority did not influence any
      parameters (such as virulence or transmission rate) that affect host population
      dynamics. We built a susceptible-infected model to examine whether the observed
      difference in coinfection virulence could impact host population dynamics under a
      range of scenarios. We found that coinfection timing can have an important but
      context-dependent effect on projected host population dynamics. Studies that
      examine only simultaneous coinfections could inflate disease impact predictions.

PMID- 29351015
TI  - Temperature-Dependent Growth and Fission Rate Plasticity Drive Seasonal and
      Geographic Changes in Body Size in a Clonal Sea Anemone.
AB  - The temperature-size rule is a commonly observed pattern where adult body size is
      negatively correlated with developmental temperature. In part, this may occur as
      a consequence of allometric scaling, where changes in the ratio of surface area
      to mass limit oxygen diffusion as body size increases. As oxygen demand increases
      with temperature, a smaller body should be favored as temperature increases. For
      clonal animals, small changes in growth and/or fission rate can rapidly alter the
      average body size of clonal descendants. Here I test the hypothesis that the
      clonal sea anemone Diadumene lineata is able to track an optimal body size
      through seasonal temperature changes using fission rate plasticity. Individuals
      from three regions (Florida, Georgia, and Massachusetts) across the species'
      latitudinal range were grown in a year-long reciprocal common garden experiment
      mimicking seasonal temperature changes at three sites. Average body size was
      found to be smaller and fission rates higher in warmer conditions, consistent
      with the temperature-size rule pattern. However, seasonal size and fission
      patterns reflect a complex interaction between region-specific thermal reaction
      norms and the local temperature regime. These details provide insight into both
      the range of conditions required for oxygen limitation to contribute to a
      negative correlation between body size and temperature and the role that fission
      rate plasticity can play in tracking a rapidly changing optimal phenotype.

PMID- 29351016
TI  - Patterns of Local Community Composition Are Linked to Large-Scale Diversification
      and Dispersal of Clades.
AB  - At any location, a group of organisms may be represented by several clades. What
      determines which clades will dominate local communities in terms of their species
      richness? Here, this relatively neglected question is addressed by analyzing 166
      local assemblages of snakes distributed globally. For most regions, local
      assemblages are dominated by clades with higher global-scale diversification
      rates and more frequent dispersal into each region, and not by clades that have
      been present in that region longer. This result contrasts with many other studies
      of local richness (in other organisms), which show strong impacts of regional
      colonization time on overall local species richness of clades. Furthermore, even
      though local assemblages are assembled independently on different continents,
      most regions have converged on similar patterns of proportional richness.
      Specifically, a few rapidly diversifying clades dominate most communities around
      the world. The high diversification rates of these clades are then linked to
      their high dispersal rates. Similar patterns may occur in many groups, such as
      plants, frogs, salamanders, birds, and mammals.

PMID- 29351017
TI  - Temperature-Dependent Species Interactions Shape Priority Effects and the
      Persistence of Unequal Competitors.
AB  - The order of species arrival at a site can determine the outcome of competitive
      interactions when early arrivers alter the environment or deplete shared
      resources. These priority effects are predicted to be stronger at high
      temperatures, as higher vital rates caused by warming allow early arrivers to
      more rapidly impact a shared environment. We tested this prediction using a pair
      of congeneric aphid species that specialize on milkweed plants. We manipulated
      temperature and arrival order of the two aphid species and measured aphid
      population dynamics and milkweed survival and defensive traits. We found that
      warming increased the impact of aphids on the quantity and quality of milkweed,
      which amplified the importance of priority effects by increasing the competitive
      exclusion of the inferior competitor when it arrived late. Warming also enhanced
      interspecific differences in dispersal, which could alter relative arrival times
      at a regional scale. Our experiment provides a first link between temperature
      dependent trophic interactions, priority effects, and dispersal. This study
      suggests that the indirect and cascading effects of temperature observed here may
      be important determinants of diversity in the temporally and spatially complex
      landscapes that characterize ecological communities.

PMID- 29351018
TI  - The Behavior and Reproductive Physiology of a Solitary Progressive Provisioning
      Vespid Wasp: Evidence for a Solitary-Cycle Origin of Reproductive Castes.
AB  - The emergence of queens and workers from solitary antecedents mark a major
      evolutionary transition in the history of life. The solitary progressive
      provisioning wasp Synagris cornuta, a member of the subfamily Eumeninae (basal to
      eusocial vespid wasps), alternates between behavioral states characterized as
      queenlike and worker-like. Akin to a queen in eusocial wasps, a S. cornuta female
      initiates construction of a cell into which she oviposits and then, similar to a
      worker, cares for the brood as it develops. The ovarian groundplan (OGP)
      hypothesis for caste origins predicts that these behavioral states are associated
      with cyclical changes in ovarian status, where females performing queenlike tasks
      have eggs and those performing worker-like tasks possess only small oocytes. Our
      findings show strong support for the OGP hypothesis: the ovaries of S. cornuta
      females undergo differential oogenesis depending on the behavioral phase: the
      largest oocyte in the ovaries of females building a cell progresses faster
      compared to that of females attending brood. Yet contrary to the OGP hypothesis,
      neither juvenile hormone nor ecdysteroids is associated with the reproductive
      cycle. Finally, the cuticular hydrocarbon profile showed no link with ovarian
      status, suggesting that fertility signals evolved subsequent to the emergence of
      group living.

PMID- 29351019
TI  - Keystone Individuals Alter Ecological and Evolutionary Consumer-Resource
      Dynamics.
AB  - Intraspecific variation is central to our understanding of evolution and ecology,
      but these fields generally consider either the mean trait value or its variance.
      Alternatively, the keystone individual concept from behavioral ecology posits
      that a single individual with an extreme phenotype can have disproportionate and
      irreplaceable effects on group dynamics. Here, I generalize this concept to
      include nonbehavioral traits and broader ecological and evolutionary dynamics. I
      test for the effects of individuals with extreme phenotypes on the ecology and
      evolution of a gall-forming fly and its natural enemies that select for opposite
      gall sizes. Specifically, I introduce a putatively keystone predator-attracting
      individual gall-maker, hypothesizing that the presence of such an individual
      should (1) increase gall maker population-level mortality, (2) cause consumer
      communities to be dominated by species that are most attracted to the keystone
      individual, (3) increase selection for traits conferring defense against the most
      common consumer, and (4) weaken patterns of stabilizing selection. I find support
      for both the ecological and evolutionary consequences of single individuals with
      extreme phenotypes, suggesting that they can be considered keystone individuals.
      I discuss the generality of the keystone individual concept, suggesting likely
      consequences for ecology and evolution.

PMID- 29351020
TI  - A Dynamic State Model of Migratory Behavior and Physiology to Assess the
      Consequences of Environmental Variation and Anthropogenic Disturbance on Marine
      Vertebrates.
AB  - Integrating behavior and physiology is critical to formulating new hypotheses on
      the evolution of animal life-history strategies. Migratory capital breeders
      acquire most of the energy they need to sustain migration, gestation, and
      lactation before parturition. Therefore, when predicting the impact of
      environmental variation on such species, a mechanistic understanding of the
      physiology of their migratory behavior is required. Using baleen whales as a
      model system, we developed a dynamic state variable model that captures the
      interplay among behavioral decisions, energy, reproductive needs, and the
      environment. We applied the framework to blue whales (Balaenoptera musculus) in
      the eastern North Pacific Ocean and explored the effects of environmental and
      anthropogenic perturbations on female reproductive success. We demonstrate the
      emergence of migration to track prey resources, enabling us to quantify the trade
      offs among capital breeding, body condition, and metabolic expenses. We predict
      that periodic climatic oscillations affect reproductive success less than
      unprecedented environmental changes do. The effect of localized, acute
      anthropogenic impacts depended on whales' behavioral response to the disturbance;
      chronic, but weaker, disturbances had little effect on reproductive success.
      Because we link behavior and vital rates by modeling individuals' energetic
      budgets, we provide a general framework to investigate the ecology of migration
      and assess the population consequences of disturbance, while identifying critical
      knowledge gaps.

PMID- 29351021
TI  - Coupling, Reinforcement, and Speciation.
AB  - During the process of speciation, populations may diverge for traits and at their
      underlying loci that contribute barriers to gene flow. These barrier traits and
      barrier loci underlie individual barrier effects, by which we mean the
      contribution that a barrier locus or trait-or some combination of barrier loci or
      traits-makes to overall isolation. The evolution of strong reproductive isolation
      typically requires the origin of multiple barrier effects. Critically, it also
      requires the coincidence of barrier effects; for example, two barrier effects,
      one due to assortative mating and the other due to hybrid inviability, create a
      stronger overall barrier to gene flow if they coincide than if they distinguish
      independent pairs of populations. Here, we define "coupling" as any process that
      generates coincidence of barrier effects, resulting in a stronger overall barrier
      to gene flow. We argue that speciation research, both empirical and theoretical,
      needs to consider both the origin of barrier effects and the ways in which they
      are coupled. Coincidence of barrier effects can occur either as a by-product of
      selection on individual barrier effects or of population processes, or as an
      adaptive response to indirect selection. Adaptive coupling may be accompanied by
      further evolution that enhances individual barrier effects. Reinforcement,
      classically viewed as the evolution of prezygotic barriers to gene flow in
      response to costs of hybridization, is an example of this type of process.
      However, we argue for an extended view of reinforcement that includes coupling
      processes involving enhancement of any type of additional barrier effect as a
      result of an existing barrier. This view of coupling and reinforcement may help
      to guide development of both theoretical and empirical research on the process of
      speciation.

PMID- 29351022
TI  - A Survey of Orthodontic Treatment in Team Care for Patients With Syndromic
      Craniosynostosis in Japan.
AB  - OBJECTIVE: To understand the actual condition of orthodontic treatment in team
      care for patients with syndromic craniosynostosis (SCS) in Japan. DESIGN: A
      nationwide collaborative survey. SETTING: Twenty-four orthodontic clinics in
      Japan. PATIENTS: A total of 246 patients with SCS. MAIN OUTCOME MEASURE:
      Treatment history was examined based on orthodontic records using common survey
      sheets. RESULTS: Most patients first visited the orthodontic clinic in the
      deciduous or mixed dentition phase. Midface advancement was performed without
      visiting the orthodontic clinic in about a quarter of the patients, and more than
      a half of the patients underwent "surgery-first" midface advancement. First-phase
      orthodontic treatment was carried out in about a half of the patients, and
      maxillary expansion and protraction were performed. Tooth extraction was required
      in about two-thirds of patients, and the extraction of maxillary teeth was
      required in most patients. Tooth abnormalities were found in 37.8% of patients,
      and abnormalities of maxillary molars were frequently (58.3%) found in patients
      who had undergone midface surgery below the age of 6 years. CONCLUSIONS: Many
      patients underwent "surgery-first" midface advancement, and visiting the
      orthodontic clinic at least before advancement was considered desirable. First
      phase orthodontic treatment should be performed considering the burden of care.
      Midface advancement below the age of 6 years had a high risk of injury to the
      maxillary molars. This survey is considered useful for improving orthodontic
      treatment in team care of patients with SCS.

PMID- 29351023
TI  - Does Talking on a Cell Phone, With a Passenger, or Dialing Affect Driving
      Performance? An Updated Systematic Review and Meta-Analysis of Experimental
      Studies.
AB  - Objective An up-to-date meta-analysis of experimental research on talking and
      driving is needed to provide a comprehensive, empirical, and credible basis for
      policy, legislation, countermeasures, and future research. Background The effects
      of cell, mobile, and smart phone use on driving safety continues to be a
      contentious societal issue. Method All available studies that measured the
      effects of cell phone use on driving were identified through a variety of search
      methods and databases. A total of 93 studies containing 106 experiments met the
      inclusion criteria. Coded independent variables included conversation target
      (handheld, hands-free, and passenger), setting (laboratory, simulation, or on
      road), and conversation type (natural, cognitive task, and dialing). Coded
      dependent variables included reaction time, stimulus detection, lane positioning,
      speed, headway, eye movements, and collisions. Results The overall sample had
      4,382 participants, with driver ages ranging from 14 to 84 years ( M = 25.5, SD =
      5.2). Conversation on a handheld or hands-free phone resulted in performance
      costs when compared with baseline driving for reaction time, stimulus detection,
      and collisions. Passenger conversation had a similar pattern of effect sizes.
      Dialing while driving had large performance costs for many variables. Conclusion
      This meta-analysis found that cell phone and passenger conversation produced
      moderate performance costs. Drivers minimally compensated while conversing on a
      cell phone by increasing headway or reducing speed. A number of additional meta
      analytic questions are discussed. Application The results can be used to guide
      legislation, policy, countermeasures, and future research.

PMID- 29351024
TI  - Does Unilateral Cleft Lip and Palate Affect the Maxillary Sinus Volume?
AB  - OBJECTIVE: The purposes of this study were to evaluate and compare the maxillary
      sinus volume (MSV) of patients with a unilateral cleft lip and palate (UCLP)
      between the cleft side and noncleft side and between adolescent patients with
      UCLP and a control (noncleft) group using cone beam computed tomography (CBCT).
      METHODS: CBCT images of 44 UCLP patients (29 males and 15 females, with a mean
      [SD] age of 13.5 [5.0] years) and 44 (22 males and 22 females, with a mean [SD]
      age 14.9 [4.2] years) age- and sex-matched controls were evaluated in this study.
      Each maxillary sinus was assessed 3-dimensionally, segmented, and its volume was
      calculated. RESULTS: There were no statistically significant differences between
      the age and gender distributions of the groups. There was a statistically
      significant difference in the MSVs of the cleft (10996.78+/-3522.89 mm3) versus
      the noncleft side (10382.3+/-3416.2 mm3; P < .05)] but no significant difference
      between the MSVs of the right and left sides ( P > .05). In the intergroup
      comparison, the mean MSVs of the UCLP patients (10701.52+/-3369.33 mm3) were
      significantly smaller than those of the control group (16054.08 +/- 5293.96 mm3;
      P < .001). CONCLUSIONS: The MSVs of the UCLP patients showed a statistically
      significant decrease compared to those of the controls ( P < .001). There was
      also a significant difference in the MSVs of the cleft and noncleft sides of the
      UCLP patients ( P < .05).

PMID- 29351025
TI  - 3D Assessment of Nasolabial Appearance in Patients With Complete Unilateral Cleft
      Lip and Palate.
AB  - OBJECTIVE: Rhinoplasty in patients with complete unilateral cleft lip and palate
      (UCLP) is challenging, and the surgical outcome of the nose is complicated to
      evaluate. The aim of this study was to assess the nasolabial appearance of
      patients with UCLP compared with a control group. DESIGN: Cross-sectional study.
      SETTING: Riga Cleft Lip and Palate Centre, Latvia. PARTICIPANTS: All consecutive
      35 patients born between 1994 and 2004 with nonsyndromic complete UCLP were
      included. Of 35 patients, 29 came for checkup; the mean age was 14.7 years (range
      10-18). In the control group, 35 noncleft participants at 10 years of age were
      included. INTERVENTIONS: Nasolabial appearance was evaluated from 3-dimensional
      images using a 3-dimensional stereo-photogrammetric camera setup (3dMDface
      System), the results being analysed statistically. RESULTS: In UCLP group, a
      statistically significant difference between cleft and noncleft side was found
      only in alar wing length ( P < .05). The difference of nasolabial anthropometric
      distances in the control group between the left and right side was not
      significant. The difference between the UCLP group and the control group was
      significant in all anthropometric distances except the lateral lip length to
      cupid's bow. CONCLUSIONS: The nasolabial appearance with acceptable symmetry
      after cleft lip and reconstructive surgery of the nose was achieved. Symmetry of
      the nasolabial appearance in patients with UCLP differed from those in the
      control group. The 3D photographs with a proposed set of anthropometric landmarks
      for evaluation of nasolabial appearance seems to be a convenient, accurate, and
      noninvasive way to follow and evaluate patients after surgery.

PMID- 29351026
TI  - The Influences of Child Intelligibility and Rate on Caregiver Responses to
      Toddlers With and Without Cleft Palate.
AB  - OBJECTIVE: The purpose of this study was to investigate the influences of child
      speech intelligibility and rate on caregivers' linguistic responses. DESIGN: This
      study compared the language use of children with cleft palate with or without
      cleft lip (CP+/-L) and their caregivers' responses. Descriptive analyses of
      children's language and caregivers' responses and a multilevel analysis of
      caregiver responsivity were conducted to determine whether there were differences
      in children's productive language and caregivers' responses to different types of
      child utterances. SETTING: Play-based caregiver-child interactions were video
      recorded in a clinic setting. PARTICIPANTS: Thirty-eight children (19 toddlers
      with nonsyndromic repaired CP+/-L and 19 toddlers with typical language
      development) between 17 and 37 months old and their primary caregivers
      participated. MAIN OUTCOME MEASURES: Child and caregiver measures were obtained
      from transcribed and coded video recordings and included the rate, total number
      of words, and number of different words spoken by children and their caregivers,
      intelligibility of child utterances, and form of caregiver responses. RESULTS:
      Findings from this study suggest caregivers are highly responsive to toddlers'
      communication attempts, regardless of the intelligibility of those utterances.
      However, opportunities to respond were fewer for children with CP+/-L.
      Significant differences were observed in children's intelligibility and
      productive language and in caregivers' use of questions in response to
      unintelligible utterances of children with and without CP+/-L. CONCLUSIONS: This
      study provides information about differences in children with CP+/-L's language
      use and caregivers' responses to spoken language of toddlers with and without
      CP+/-L.

PMID- 29351027
TI  - Custom-Made Palatal Shield Use in Cleft Palate and Fistula Repair: A Potential
      Benefit for Fast Postoperative Recovery.
AB  - OBJECTIVE: To review our experience with a polymethylmethacrylate (PMMA)
      protective shield used as an adjunct to protect the newly restored palate in wide
      bilateral cleft and complex fistula closure without diet restrictions. DESIGN:
      Clinical cohort study. SETTING: Division of Plastic Surgery and Maxillary
      Surgery. PATIENTS: A selection of 22 cleft palate children undergoing (tertiary)
      palatal fistula repair (n = 16) or closure of a complex wide primary palatal
      defect (n = 6). INTERVENTIONS: One month prior to surgery, a plaster model of the
      palate was made adding a 5- to 8-mm-thick layer of dental putty to the level of
      the dental arch. On top of the putty, a 1.5-mm-thick PMMA shield was created to
      cover the postoperative elevated and restored palate. MAIN OUTCOME MEASURES:
      Fistula recurrence rate, postoperative complications, days of hospitalization.
      RESULTS: All patients maintained durable and safe palatal closure without fistula
      recurrence within the follow-up period, varying from 1 until 4 years. Recovery
      was fast, with a mean duration of hospitalization of 1.5 days. All patients could
      directly resume their normal diet. CONCLUSIONS: A PMMA shield has been shown to
      be a safe and helpful adjunct in complex fistula repair and late anterior palate
      repair.

PMID- 29351028
TI  - Female and Male Differences in Academic Achievement in Individuals With Cleft: A
      Population-Based Register Study.
AB  - OBJECTIVE: The focus of this study was to determine if there is any significant
      difference in academic achievement for girls and boys with a cleft compared to
      the general population of Swedish students at graduation from compulsory school.
      DESIGN: A retrospective population-based study using data obtained from the
      Swedish Medical Birth Register that was linked to the Swedish School-Grade
      Register. PARTICIPANTS: Two hundred seventy girls and 241 boys with cleft palate
      (CP), 222 girls and 429 boys with cleft lip (CL), and 299 girls and 531 boys with
      cleft lip and palate (CLP) were compared with the compulsory school population
      comprising 609,397 girls and 640,007 boys. MAIN OUTCOME MEASURES: (1) Odds of
      receiving the lowest grade and reduced odds in receiving high grades in
      Mathematics, English, and Swedish. (2) grade point average (GPA). RESULTS: In all
      3 subject grades, for boys with cleft there was no difference when compared to
      the male population. Girls with cleft were similar to their peers with a few
      exceptions. Girls with CLP had lower Math grades, and girls with CP had lower
      Math, English, and Swedish grades. Girls with CP and CLP achieved a significantly
      lower GPA in comparison to the female population and boys with CP and CL achieved
      lower GPAs in comparison to the male population. CONCLUSIONS: This study
      indicates that educational outcomes for girls with cleft are more negatively
      affected than for boys with cleft.

PMID- 29351029
TI  - Factors Associated With Adherence to Nasoalveolar Molding (NAM) by Caregivers of
      Infants Born With Cleft Lip and Palate.
AB  - OBJECTIVE: Identify factors associated with adherence to nasoalveolar molding
      (NAM) therapy. DESIGN: Retrospective case-control study. SETTING: Tertiary
      referral center. PATIENTS, PARTICIPANTS: Infants with cleft lip, with or without
      cleft palate, referred for NAM. One hundred thirty-five patients met criteria.
      MAIN OUTCOME MEASURE(S): Adherence to NAM therapy, defined as continuous use of
      the appliance and attendance of NAM adjustment visits. RESULTS: Female sex (OR =
      2.85, 95% CI 1.21-6.74), bilateral cleft (OR = 2.88, 95% CI 1.29-6.46), and
      travel distance (OR = 1.01, 95% CI 1.00-1.01) were independent predictors of
      nonadherence. Bilateral clefts (OR = 8.35, 95% CI 2.72-25.64) and public-payer
      insurance (OR = 3.67, 95% CI 1.13-11.91) for male patients were significantly
      associated with nonadherence, in our sex-stratified multivariate model. The
      majority of the families (58%) had public health insurance. Males comprised 77.0%
      of the cohort. CONCLUSIONS: NAM treatment adherence is impaired by bilateral
      clefts, female sex, increased travel distance, and public insurance. Further
      studies are warranted to investigate how these factors affect adherence, and to
      develop interventions to improve adherence in families at risk due to economic or
      psychosocial barriers.

PMID- 29351030
TI  - Vocal Loudness as Contributory to the Occurrence of Obligatory Posterior Nasal
      Turbulence.
AB  - Two cases are presented that show increased loudness as contributory to the
      occurrence of audible posterior nasal turbulence as an obligatory symptom. Case 1
      was an 18-month-old boy with repaired cleft palate who exhibited sporadic
      posterior nasal turbulence with velar flutter that was associated with increased
      loudness. Case 2 was a 4-year-old boy with repaired cleft palate who exhibited
      relatively frequent posterior nasal turbulence with velar flutter that was
      associated with pervasive and excessive loudness. Following 3 therapy sessions,
      loudness was reduced and audible nasal turbulence was eliminated. Clinical
      implications are discussed.

PMID- 29351032
TI  - Speech and Language Performance of US-Born and Internationally Adopted Toddlers
      With Cleft Lip and Palate.

PMID- 29351031
TI  - Strengths and Difficulties Questionnaire (SDQ): Informant Agreement Between
      Children Born With Cleft Lip and/or Palate and Their Parents.
AB  - OBJECTIVE: Informant discrepancies on psychological measures may affect the
      assessment, classification, and treatment of children's mental health.
      Concordance between different informants has been shown to be low to moderately
      correlated. The present study examined the agreement between children with cleft
      lip and/or palate (CL/P) and their parents. DESIGN: Cross-sectional data from 7
      consecutive birth cohorts based on routine psychological assessments at age 10
      with comparisons to national reference groups. SETTING: Centralized and
      multidisciplinary treatment setting. PARTICIPANTS: 323 children age 10, born with
      CL/P and their parents (participation rate: 89%). OUTCOME MEASURES: Strengths and
      Difficulties Questionnaire (SDQ). RESULTS: Children born with CL/P and their
      parents tend to follow similar patterns of disagreement on the SDQ as reported in
      the general population, with children reporting more symptoms than their parents,
      and boys having more problems than girls on most subscales. Child and parent
      reports were low to moderately correlated, and not affected by the child's gender
      or the presence of conditions additional to the cleft. CONCLUSIONS: Differences
      between informants on the SDQ reflect different perspectives of the child's
      adjustment, and both informants are important in the assessment of mental health.
      Children with CL/P and their parents do not significantly differ from children
      and parents in the general population on their agreement of the child's
      psychological adjustment. As with the general population, clinical assessments
      should be based on a mixture of both informants' reports.

PMID- 29351033
TI  - Closing the Loop on Centralization of Cleft Care in the United Kingdom.
AB  - OBJECTIVE: We highlight a major study that investigated the impact of
      reconfigured cleft care in the United Kingdom some 15 years after centralization.
      We argue that centralization as an intervention has a major impact on outcomes.
      SETTING: Audit clinics held in Cleft Centers in the United Kingdom. PATIENTS,
      PARTICIPANTS: Five-year-olds born between April 1, 2005, and March 31, 2007, with
      nonsyndromic unilateral cleft lip and palate. INTERVENTIONS: Centralization of
      cleft care. MAIN OUTCOME MEASURE(S): We collected routine clinical measures
      (speech recordings, hearing, photographs, models, oral health, psychosocial
      factors) in a very similar way to a previous survey. RESULTS: We identified 359
      eligible children and recruited 268 (74.7%) to the study. Overall, their outcomes
      were better post-centralization. There have been marked improvements in
      dentoalveolar arch relationships and in speech whereas the prevalence of dental
      caries and hearing loss are unchanged. CONCLUSIONS: Centralized cleft care has
      changed UK outcomes considerably and there is no argument for returning to a
      dispersed model of treatment.

PMID- 29351034
TI  - Postoperative Complications Following LeFort 1 Maxillary Advancement Surgery in
      Cleft Palate Patients: A 5-Year Retrospective Study.
AB  - OBJECTIVE: To investigate the postoperative complication rates of LeFort 1
      maxillary advancement surgery in cleft patients when performed by a single
      surgeon over a 5-year period. DESIGN: A retrospective case note review of 79
      cleft palate patients. SETTING: All surgery was performed by a single oral and
      maxillofacial surgeon in a tertiary care center. PARTICIPANTS: All cleft palate
      patients over 17 years of age who opted for surgical correction of maxillary
      hypoplasia with a LeFort 1 between 2010 and 2015. Patients required full surgical
      and clinical records. INTERVENTIONS: Complete surgical advancement of the maxilla
      ranging from 2.0 to 18.0 mm performed by conventional osteotomies (87%) or
      distraction osteogenesis (13%). MAIN OUTCOME MEASURE(S): Postoperative patient-
      and clinician-reported complications at set-interval follow-up appointments.
      RESULTS: Twenty-one patients (26.58%) reported no complications; 11 postoperative
      complications were identified in the remaining cohort. Temporary paresthesia of
      the infraorbital nerve was the most common complication (53.16%) followed by
      infection (13.92%). Other complications included relapse (11.39%), maxillary
      instability (6.33%), velopharyngeal impairment (6.33%), nasal obstruction
      (5.06%), chronic sinusitis (3.80%), bony dehiscence (1.27%), gingival necrosis
      (1.27%), partial necrosis of the maxilla (1.27%), and loss of tooth vitality
      (1.27%). CONCLUSIONS: LeFort 1 maxillary advancement surgery in cleft palate
      patients is associated with a wide range of postoperative complications, most
      commonly temporary paresthesia of the infraorbital nerve. Detailed, informed
      consent is essential prior to surgery.

PMID- 29351035
TI  - Conscious Perception of Facial Asymmetry in a Unilateral Cleft Lip Model.
AB  - OBJECTIVE: Lip asymmetry after a unilateral cleft lip repair can be perceived as
      an unsatisfactory result. The objective of this study is to determine the degree
      of upper lip asymmetry and/or nasal alar hooding required for recognition of
      asymmetry in a simulated model of unilateral cleft lip. DESIGN: A model of
      unilateral cleft lip was created using digital morphing software to simulate
      asymmetries in vermilion height and nasal hooding in photographs of children.
      Volunteers were shown photographs for different time intervals and with varying
      degrees of asymmetry. Ability to detect facial asymmetry was recorded and
      analyzed. SETTING: This study was conducted by surveying layperson volunteers in
      public community settings. PARTICIPANTS: 108 layperson volunteers were randomly
      surveyed. MAIN OUTCOME MEASURES: The primary outcome measure was a reported lip
      or nose asymmetry by the volunteers. Proportions and corresponding 95% confidence
      intervals were obtained to estimate the probability of reporting an asymmetry at
      3- and 10-second intervals. RESULTS: After 3- and 10-second exposure, labial
      asymmetry was perceived by >=50% of subjects at 2 mm (62%, P = .001) and 1 mm
      (89%, P < .0001), respectively. Nasal asymmetry was detected by <50% of subjects
      at 3 seconds, but >=50% perceived a 3-mm alteration at 10 seconds (64%, P <
      .0001). Photographs with combined nasal and labial modification did not lower the
      threshold for asymmetry perception compared to either deformity alone.
      CONCLUSIONS: This study is the first to determine a predictable millimeter
      threshold for perceived asymmetry in cleft lip deformity using a digital model.

PMID- 29351036
TI  - Crouzon with Acanthosis Nigricans and Odontogenic Tumors: A Rare Form of
      Syndromic Craniosynostosis.
AB  - Crouzon syndrome with acanthosis nigricans (CAN) is caused by a mutation in the
      fibroblast growth factor receptor ( FGFR) 3 gene that presents clinically as
      Crouzonoid craniofacial features in association with other anomalies such as
      acanthosis nigricans and benign odontogenic tumors. Diagnosis through the use of
      genetic mutational analysis is critical, as it alerts the surgeon to the need for
      careful screening for jaw tumors so that timely treatment in the form of
      curettage or segmental resection can be provided.

PMID- 29351037
TI  - Lingual Pressure During Dingman-Assisted Cleft Palate Repair: An Investigatory
      Case Series.
AB  - BACKGROUND: A variety of palatoplasty techniques are used for cleft palate
      repair, almost all involving a device called the Dingman-Grabb mouth gag
      ("Dingman") to push the tongue and cheeks out of the way of the operating field.
      There have been numerous case reports of complications hypothesized to be due to
      the gag, such as lingual edema and airway obstruction. The purpose of this study
      is to introduce a technique for monitoring lingual pressure during Dingman
      assisted palatoplasty and present preliminary data from a small series. METHODS:
      Patients with a cleft palate who underwent palatoplasty with the assistance of a
      Dingman-Grabb retractor at the Mount Sinai Hospital were eligible. Patients
      underwent a palatoplasty while having their lingual pressure monitored using a 23
      gauge needle inserted into the tongue and connected to a pressure monitor.
      RESULTS: Three patients were included. Patients 1 and 2 experienced a rapid rise
      in lingual pressure over the course of the first 45 minutes of the palatoplasty
      before plateauing until the conclusion of the operation when the Dingman was
      released. Patient 3 plateaued almost immediately by minute 1 and then had a rise
      in lingual pressure during the latter half of the operation, reaching a peak
      pressure immediately before the end of the operation. CONCLUSIONS: The present
      study describes an easy method to monitor lingual pressure that succeeded in
      measuring such changes throughout 3 palatoplasties and confirming the acute rise
      in lingual pressure and the potential danger posed to the tongue and the airway
      through the use of the Dingman.

PMID- 29351038
TI  - Early Reading Abilities of Bilingual Children With Nonsyndromic Orofacial Clefts.
AB  - OBJECTIVE: To investigate the early reading abilities, and related cognitive
      linguistic processes, in bilingual children with nonsyndromic cleft lip and/or
      palate (CL/P), and to identify deficits that might be amenable to intervention.
      DESIGN AND PARTICIPANTS: Bilingual participants with CL/P aged 5 to 6 years who
      were English-dominant ( n=17) or Mandarin-dominant ( n=18) were recruited using
      consecutive sampling from a national cleft treatment center and matched pairwise
      to a sample of typically developing (TD) children on language dominance, age, and
      socioeconomic status. All participants were assessed in English on single-word
      reading accuracy using the Wide Range Achievement Test (4th Ed), and key
      cognitive-linguistic factors associated with reading development: phonological
      awareness, rapid automatized naming (RAN), receptive and expressive vocabulary,
      and verbal short-term and working memory. RESULTS: CL/P and TD groups were
      compared within language dominance group (Mandarin or English) for all measures.
      The Mandarin-dominant CL/P group had significantly poorer reading accuracy and
      phonological awareness than their TD peers. Additionally, regardless of language
      dominance, faster RAN correlated significantly with better reading accuracy in
      both the CL/P groups but not the TD groups. CONCLUSIONS: Children with CL/P who
      are learning English as a second language are at greater risk of reading
      difficulties. Furthermore, the cognitive-linguistic processes underlying early
      reading in bilingual children with CL/P differ from those of their TD peers.
      Routine screening and tailored intervention is advisable.

PMID- 29351039
TI  - Resorbable Plates in Secondary Cleft Nasal Reconstruction.
AB  - OBJECTIVE: The authors report on the use and complications of alloplastic
      resorbable plates and compare their use to autologous cartilage grafts in
      secondary cleft nasal reconstruction. DESIGN: Institutional review board (IRB)
      approved retrospective chart review. SETTING: Texas Cleft-Craniofacial Center at
      the McGovern Medical School at the University of Texas Health Sciences Center at
      Houston. PATIENTS: Patients with unilateral or bilateral cleft lip nasal
      deformity who have undergone secondary correction of their nasal deformity with
      at least 1-year follow-up. INTERVENTIONS: During their reconstruction, some
      patients had cartilage grafts used for support, whereas others were reconstructed
      using resorbable plates. MAIN OUTCOME MEASURE(S): Complications (exposure,
      infection, malposition, hematoma/seroma) and rates of tertiary revisions.
      RESULTS: 197 patients underwent secondary cleft nasal reconstruction, with 30
      patients in the resorbable plate group and 32 in the cartilage graft group. Age
      at surgery was 8.5+/-4.1 years with resorbable plates and 11.0+/-4.8 years with
      cartilage graft ( P = .03). Infection rate in the resorbable plate group and
      cartilage graft group were 0% and 3.25% ( P = 1). Extrusion occurred in 3 of the
      absorbable plate group and 2 patients with cartilage graft ( P = .67). Additional
      surgery was recorded in 43.3% of the resorbable plate group versus 53.1% of the
      cartilage graft group ( P = .459). CONCLUSION: The data provide evidence that the
      use of alloplastic resorbable plate in the pediatric population is a safe
      alternative to autologous septal cartilage in secondary cleft nasal
      reconstruction. There is no statistical difference in short-term complications or
      the incidence of additional nasal surgery.

PMID- 29351040
TI  - Respiratory Polysomnographic Findings in Patients Treated Primarily for
      Unilateral Cleft Lip and Palate.
AB  - Cleft lip and palate (CLP) is the most common congenital craniofacial
      abnormality. Obstructive sleep apnea syndrome (OSAS) is a highly prevalent but
      underdiagnosed disease and is frequently associated with craniofacial anomalies.
      There are few studies describing the sleep breathing pattern of children with
      CLP. This study sought to characterize the respiratory profile of 23 children
      with unilateral cleft lip and palate, aged 7-12 years, who had undergone cleft
      lip and nasal repair at age 3-4 months and palatoplasty at 12-15 months, with a
      particular focus on evaluating the presence of OSAS in children with CLP.
      Polysomnography was performed and findings were analyzed descriptively. We found
      a mean and median for apnea/hypopnea index (AHI) of 1.11/h (SD = 0.78) and 0.9/h,
      respectively. The mean obstructive apnea index (OAI) was 0.27/h (SD = 0.38) and
      the median, 0.1/h. Nearly 30% of patients had an AHI above 1.4 events/h. There
      was no significant oxyhemoglobin desaturation in the study group. In this group,
      the prevalence of OSAS was higher than in noncleft populations when compared to
      the normality values adopted. This sample of patients with unilateral cleft lip
      and palate exhibited an increased prevalence of OSAS during the mixed dentition
      stage. Although the results showed that OSAS was mild, we advise closer
      observation of these patients. Polysomnography is recommended for the assessment
      of children with airway abnormalities, to individualize the extent of treatment.

PMID- 29351041
TI  - A New Technique in Alveolar Cleft Bone Grafting for Dental Implant Placement in
      Patients With Cleft Lip and Palate.
AB  - OBJECTIVE: To evaluate 2 iliac corticocancellous-block grafting techniques for
      dental implant placement in residual alveolar clefts. DESIGN: Nonrandomized
      prospective clinical trial between March 2010 and December 2014. SETTING:
      National Hospital of Odonto-Stomatology, Hanoi, Vietnam. PARTICIPANTS: Thirty-two
      patients (23 female, 9 male; mean age, 21.28 years; range, 16-31 years) with
      unilateral complete alveolar cleft after reconstructive surgery for cleft lip and
      palate (CLP). INTERVENTIONS: Harvested iliac crest bone was cut into 2
      corticocancellous blocks. The smaller block was adapted against the sutured nasal
      mucoperiosteum and overlaid with cancellous bone; the larger one overlapped the
      labial cleft margin and was fixed with screws. Endosteal dental implants were
      placed after 4 to 6 months, and final restorations were delivered 6 months later.
      MAIN OUTCOME MEASURES: Flap statuses were assessed clinically. Bone formation was
      assessed using the Enemark scale. Cone-beam computed tomography was used for
      graft height and width measurements. Implant health was assessed by the Misch
      criteria. RESULTS: The mean postgrafting follow-up period was 36.7 +/- 10.4
      (range, 18-53) months. Three patients (9.4%) showed flap dehiscence but no
      infection 7 days after bone grafting. Twenty-nine patients (90.6%) had 75% to
      100% bone fill (Enemark score of 1). The mean graft height and width were 11.4 +/
      2.4 and 6.1 +/- 1.0 mm, respectively. Sufficient bone for implant placement was
      noted in 29 patients (90.6%); the others required partially fixed prostheses. All
      implants functioned for at least 18 months. CONCLUSION: The proposed technique is
      reliable to reconstruct the alveolar cleft for implant placement in CLP patients.

PMID- 29351042
TI  - Secondary Alveolar Bone Grafting in Patients Born With Unilateral Cleft Lip and
      Palate: A 20-Year Follow-up.
AB  - OBJECTIVE: To identify factors of oral health important for the final outcome,
      after secondary alveolar bone grafting in patients born with unilateral cleft lip
      and palate and compare occlusal radiographs with cone beam computed tomography
      (CBCT) in assessment of alveolar bone height. DESIGN: Observational follow-up
      study. SETTING: Cleft Lip and Palate Team, Craniofacial Center, Uppsala
      University Hospital, Sweden. PATIENTS: 40 nonsyndromic, Caucasian patients with
      unilateral complete cleft lip and palate. INTERVENTIONS: Clinical examination,
      CBCT, and occlusal radiographs. MAIN OUTCOME MEASUREMENTS: Alveolar bone height
      was evaluated according to Bergland index at a 20-year follow-up. RESULTS: The
      alveolar bone height in the cleft area was significantly reduced compared to a
      previously reported 10-year follow-up in the same cohort by total ( P = .045) and
      by subgroup with dental restoration ( P = .0078). This was positively correlated
      with the gingival bleeding index (GBI) ( r = 0.51, P = .0008) and presence of
      dental restorations in the cleft area ( r = 0.45, P = .0170). There was no
      difference in the Bergland index generated from scoring the alveolar bone height
      on occlusal radiographs as with the equivalent index on CBCT. CONCLUSION:
      Patients rehabilitated with complex dental restoration seems to be at higher risk
      for progression of bone loss in the cleft area. Supportive periodontal therapy
      should be implemented after complex dental restorations in cleft patients.
      Conventional occlusal radiographs provide an adequate image for evaluating
      postoperative bone height in clinical follow-up.

PMID- 29351043
TI  - Congenital Midline Upper Lip Sinuses: 3 Rare Cases.
AB  - Congenital sinuses of the upper lip are rare congenital malformations. There have
      been only 40 cases described in the literature. We report 3 cases of congenital
      midline upper lip sinus in Caucasian children. Two of those lesions were
      associated with other anomalies (complete cleft palate and hemifacial macrosomia
      or submucous cleft palate with bifid uvula). The pathophysiology remains
      unexplained yet. Congenital upper lip sinuses can be considered as possible
      microforms of cleft-lips. Associated anomalies are frequent and must be sought.
      The treatment is a full excision of the sinus tract and of the skin around the
      punctum in order to avoid risks of recurrence.

PMID- 29351044
TI  - Comparison of Reliability of Categorical and Continuous Scales for Radiographic
      Assessments of Bone Infill Following Secondary Alveolar Bone Grafting.
AB  - OBJECTIVES: To investigate examiner reliability of scoring intraoral radiographs
      of bone infill following secondary bone grafting using a categorical scale
      (modified Kindelan Index) and a 10-cm visual analog scale (VAS). To investigate
      the level of clinical experience on the reliability of these assessments. DESIGN:
      Retrospective study involving 10 clinicians of varying clinical experience who
      were blind to the patient's identity. SETTING: All grafting was carried out
      within the New Zealand public hospital service. PATIENTS: Fifty-eight grafts (48
      UCLP and 5 BCLP) were assessed with 14 duplicated radiographs randomly added to
      the sample, making a total of 72 radiographs for assessment. MAIN OUTCOME
      MEASURES: Weighted kappa was used for intra- and interrater examiner reliability
      for the categorical scale and correlations for the VAS. RESULTS: Relatively poor
      intrarater examiner agreement for categorical scoring (median 0.46) was found.
      Clinicians with greater experience generally recording higher intrarater weighted
      kappa. The intrarater correlations for the continuous scale (median 0.89) suggest
      better consistency regardless of the level of experience. The interrater
      relationships were generally low, with an average of weighted kappa of 0.25 while
      the overall average VAS correlation was 0.49. For the majority of scorers, there
      was a relationship between the VAS and the Kindelan Index, with lower VAS scores
      related to worse Kindelan scores. CONCLUSIONS: The use of a VAS produced better
      intra- and interexaminer reliability than the categorical Kindelan Index and was
      more consistent despite the level of clinical experience. Further evaluation of
      the validity of the VAS for the assessment of bone infill is warranted.

PMID- 29351045
TI  - Gender Views and Relationships in Families of Children With Craniofacial
      Differences.
AB  - OBJECTIVE: Gender values and beliefs are known to influence family functioning.
      The aim of the current study was to describe the association between views about
      gender and family functioning within families with a child with a craniofacial
      difference (CFD). DESIGN: Participants included 74 dyads composed of children (8
      18 years old) with CFD (n = 36 female), including cleft lip/palate, and a parent
      (n = 56 female). Children and caregivers both completed the activities subscale
      of the Occupations, Activities, and Traits-Attitudes Measure (C/OAT-AM). Children
      completed selected items from the Parent Perception Inventory (PPI). Caregivers
      completed the nurturance subscale of the Parenting Dimensions Inventory-Short
      Form (PDI-S) and the Parenting Stress Scale (PSS). SETTING: Participants were
      recruited from an outpatient program at an academic medical center. RESULTS:
      There were no significant relationships among the participant demographics and
      the study variables, with the exception that more complex CFD diagnoses were
      correlated with increased parenting stress. General linear modeling showed that
      parents with more flexible gender attitudes reported more nurturing parenting
      behaviors. There was also a positive association between parental flexibility in
      gender views and child-reported parent-child relationship quality. An interaction
      showed that the relationship between parental flexibility in gender views and
      child-reported relationship quality was stronger for females and nonsignificant
      for males. CONCLUSIONS: Caregivers with more flexible gender attitudes perceived
      themselves as more nurturing and were seen more positively by their daughters
      with a CFD. This pattern may inform parenting interventions for CFD populations.

PMID- 29351046
TI  - Young Adults' Experience of Appearance-Altering Orthognathic Surgery: A
      Longitudinal Interpretative Phenomenologic Analysis.
AB  - OBJECTIVE: To gain an experiential account of the processes of change associated
      specifically with orthognathic surgery. DESIGN: A qualitative design was used.
      Semistructured interviews were carried out with 7 participants approximately 1
      week before and 6-8 weeks after surgery. The data were analyzed using
      interpretative phenomenologic analysis (IPA). SETTING: Participants were
      recruited from a NHS Dental Hospital. PARTICIPANTS: Patients aged 16 to 25 years
      scheduled to undergo orthognathic surgery on both the upper and lower jaws were
      purposively sought to participate. Seven participants aged between 18 and 25
      years and who had undergone a bimaxillary osteotomy completed interviews (5
      females and 2 males). RESULTS: Themes were identified in connection with the
      overall journey of treatment being a rite of passage; the treatment's role in
      raising awareness about the anomalies in appearance; the initial shock at the
      changes that followed surgery; the uncertainty about treatment; the impact of
      actual negative reactions of others; and the role of significant others in the
      decision-making process. CONCLUSIONS: Participants described undergoing a much
      more complex process of adjustment to change in appearance than has been
      identified elsewhere within the literature, and the study highlights the nuanced
      fashion in which both medical and parental communication influence patient
      expectation and experience of surgery. There is a need to improve communication
      between clinicians, families, and young adults seeking orthognathic surgery.
      Further studies are needed to investigate the processes associated with seeking
      to change facial appearance resulting from other forms of dentofacial condition.

PMID- 29351047
TI  - Otologic Disease Following Palatoplasty In International Cleft Palate Cohort.
AB  - OBJECTIVE: Study the prevalence of otologic disease in a pediatric post
      palatoplasty population with no prior ear tube placement in resource-deprived
      countries and assess patient characteristics associated with these abnormal
      results. DESIGN: Retrospective data review. PARTICIPANTS: Ecuadorian and Chinese
      children identified during humanitarian cleft lip and palate repair trips with
      cleft palates undergoing palatoplasty from 2007 to 2010. INTERVENTIONS:
      Tympanometry and otoacoustic emission (OAE) testing performed following
      palatoplasty. Patients' parents administered surveys regarding perceived hearing
      deficits. MAIN OUTCOME MEASURES: Age, gender, Veau classification, follow-up
      time, laterality, and country of origin were evaluated for possible association
      with type B tympanogram, "Refer" Otoacoustic results, and presence of hearing
      difficulty as identified by a parent. Significant predictors were further
      evaluated with multivariate analysis. RESULTS: The cohorts included 237 patients
      (129 Ecuadorian, 108 Chinese); mean age: 3.9 years; mean follow-up: 4.2 years.
      Thirty-nine percent scored type B, 38% failed OAE testing, and 8% of parents
      noted hearing deficits. The country of origin and a younger age were identified
      as predictive variables regarding type B tympanogram. Follow-up time, country of
      origin, and bilateral OAE "Refer" results all significantly predicted parental
      questionnaire results. Subsequent multivariable analysis further demonstrated
      effect modification between the 2 variables of age at palatoplasty and country of
      origin when predicting type B vs type A tympanometry. CONCLUSION: Without
      otologic intervention, cleft palate children in resource-deprived settings suffer
      type B tympanometry and failed OAE results with similar to increased incidences
      to other studied cleft palate populations with otologic interventions available.

PMID- 29351048
TI  - Academic-Community Partnership Educating Children About Weather-Related Disaster
      Preparedness.
AB  - Children are a population that has an increased risk of harm during any disaster
      events. This risk can be decreased by educating children in disaster preparedness
      skills. This article outlines a basic modifiable curriculum for teaching weather
      related disaster preparedness to children ages 10-13, and shares how this was
      accomplished at an elementary school in North Alabama through a collaboration
      between the school and a local college of nursing.

PMID- 29351049
TI  - School Nursing EBP Clinical Guidelines: What They Are and Are Not, and Why They
      Matter.
AB  - Quality school nursing practice should be evidence-based. However registered
      nurses in autonomous school nursing practice have limited capacities to access,
      synthesize, and implement the best evidence into practice. Clinical guidelines
      are important tools to reduce barriers to evidence-based practice (EBP) and
      support the delivery of high-quality school nursing care. The purpose of this
      article is to outline what EBP clinical guidelines are, are not, and why they
      matter.

PMID- 29351050
TI  - Hidden Medical Devices in the School Setting: What the School Nurse Needs to Know
      About the Safe Use of Baclofen Pumps.
AB  - One of the "hidden" medical devices in the school setting is the baclofen pump,
      which is used for the treatment of spasticity. The goals of spasticity treatment
      are to decrease muscle tone, deformity, and pain in order to maximize function
      and ease of care for both child and caregiver. The use of an intrathecal baclofen
      pump, often for children with cerebral palsy, spinal cord injury, brain injury,
      or stroke, has been effective in spasticity treatment. It is important for school
      nurses to be aware of the safety implications associated with this type of
      device. The Specialized Health Needs Interagency Collaboration (SHNIC) program at
      the Kennedy Krieger Institute has complied education and materials that explain
      the use of baclofen pumps in children with spasticity and the role of the school
      nurse in providing staff training, developing emergency care plans, and creating
      a safe school environment for children with special health needs.

PMID- 29351051
TI  - Voluntary ambulation using voluntary upper limb muscle activity and Hybrid
      Assistive Limb(r) (HAL(r)) in a patient with complete paraplegia due to chronic
      spinal cord injury: A case report.
AB  - CONTEXT: We sought to describe our experience with the Hybrid Assistive Limb(r)
      (HAL(r)) for active knee extension and voluntary ambulation with remaining muscle
      activity in a patient with complete paraplegia after spinal cord injury.
      FINDINGS: A 30-year-old man with complete paraplegia used the HAL(r) for 1 month
      (10 sessions) using his remaining muscle activity, including hip flexor and upper
      limb activity. Electromyography was used to evaluate muscle activity of the
      gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in
      synchronization with the Vicon motion capture system. A HAL(r) session included a
      knee extension session with the hip flexor and voluntary gait with upper limb
      activity. After using the HAL(r) for one month, the patient's manual muscle hip
      flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the
      left knee, and from 0/5 to 1/5 for the extension of both knees.
      CONCLUSION/CLINICAL RELEVANCE: Knee extension sessions with HAL(r), and hip
      flexor and upper-limb-triggered HAL(r) ambulation seem a safe and feasible option
      in a patient with complete paraplegia due to spinal cord injury.

PMID- 29351052
TI  - Particulate Coral Hydroxyapatite Sheltered by Titanium Mesh for Localized
      Alveolar Rehabilitation After Onlay Graft Failure: A Case Report.
AB  - Reconstruction of bone loss in the alveolar ridge has long been challenging.
      Autologous bone grafts are considered as the "golden standard," while little
      research has focused on how to repair pronounced alveolar bone defects after
      autologous bone graft failure. The aim of this study was to detail a method based
      on the titanium mesh technique coupled with particulate coral hydroxyapatite to
      solve the onlay graft failure. With bone deficiency in the No. 11 and No. 24-25
      regions, we harvested 2 autologous bone blocks for reconstruction. Two weeks
      after transplantation, the graft in the No. 11 region had healed uneventfully,
      while the graft in the anterior mandible became infected because of soft tissue
      dehiscence. After removal of the failed autologous bone block, pure coral
      hydroxyapatite stabilized within titanium mesh was used for alveolar
      rehabilitation. Six months later, the width of the local alveolar bone was
      evaluated. After the titanium mesh was removed, a biopsy was performed to study
      bone regeneration by micro computerized tomography and histology, following by a
      standard Straumann implant insertion. Although there was wound dehiscence 14 days
      after bone augmentation, repeated local rinsing and anti-inflammation therapy
      controlled the inflammatory reaction. The total horizontal bone gain was 4.2 +/-
      0.5 mm. Micro computerized tomography revealed that the closer the coral
      hydroxyapatite was to the host bone, the more was resorbed and the more bone
      regenerated. Histology showed mature lamellar bone structures, with evident
      residual coral hydroxyapatite. A 3-year follow-up revealed stable bone around the
      dental implant and successful function of the implant-born prosthesis. This study
      proposes that the method of particulate coral hydroxyapatite sheltered by
      titanium mesh is a promising solution in handling alveolar bone augmentation
      failure. More cases are needed for further research to form an efficient
      treatment procedure.

PMID- 29351053
TI  - Patient Variability Seldom Assessed in Cost-effectiveness Studies.
AB  - BACKGROUND: Cost-effectiveness analysis (CEA) estimates can vary substantially
      across patient subgroups when patient characteristics influence preferences,
      outcome risks, treatment effectiveness, life expectancy, or associated costs.
      However, no systematic review has reported the frequency of subgroup analysis in
      CEA, what type of heterogeneity they address, and how often heterogeneity
      influences whether cost-effectiveness ratios exceed or fall below conventional
      thresholds. METHODS: We reviewed the CEA literature cataloged in the Tufts
      Medical Center CEA Registry, a repository describing cost-utility analyses
      published through 2016. After randomly selecting 200 of 642 articles published in
      2014, we ascertained whether each study reported subgroup results and collected
      data on the defining characteristics of these subgroups. We identified whether
      any of the CEA subgroup results crossed conventional cost-effectiveness
      benchmarks (e.g., $100,000 per QALY) and compared characteristics of studies with
      and without subgroup-specific findings. RESULTS: Thirty-eight studies (19%)
      reported patient subgroup results. Articles reporting subgroup analyses were more
      likely to be US-based, government funded (v. drug industry- or nonprofit
      foundation-funded) studies, with a focus on primary or secondary (v. tertiary)
      prevention (P < 0.05 for comparisons). One or more patient characteristics were
      used to stratify CEA results 68 times within the 38 studies, with most
      stratifications using one characteristic (n = 47), most commonly age (n = 35).
      Among the 23 stratifications reported alongside average ratios in US studies, 13
      produced subgroup ratios that crossed a conventional CEA ratio benchmark.
      CONCLUSIONS: Most CEAs do not report any subgroup results, and those that do most
      often stratify only by patient age. Over half of the subgroup analyses reported
      could lead to different value-based decision making for at least some patients.

PMID- 29351054
TI  - Xyloglucans fucosylation defects do not alter plant boundary domain definition.
AB  - The CUP-SHAPED COTYLEDON (CUC) transcription factors play a fundamental role in
      plant morphogenesis by defining boundary domains throughout plant development.
      Despite their central roles in plant development, little is known about the CUC
      molecular network. In a recent work, we identified a role for MUR1, a protein
      involved in the production of GDP-L-Fucose, in this network and showed that
      fucose per se is required for proper boundary definition in various developmental
      contexts. Which pathway involving fucose is required to determine boundary is not
      yet known. Here, we use a previously described mutant and transgenic line with
      reduced fucosylated xyloglucans (XyG) to explore one such pathway. By
      quantitatively comparing leaf shape, we show that defects in XyG fucosylation do
      not impact leaf serrations development suggesting that fucose absence in XyG does
      not impact boundary development in mur1-1 mutant. Thus another - not yet
      identified - pathway or fucosylated compound contribute to boundary domain
      definition.

PMID- 29351055
TI  - Are pre-terms born timely and right immunized? Results of an Italian cohort
      study.
AB  - The aim of this study is to evaluate the vaccination coverage at 24 months of
      chronological age in a sample of preterm infants discharged by the Neonatal
      Intensive Care Unit (NICU) of the Bari Policlinico University General Hospital in
      Italy. The list of infants preterm born discharged during 2013 by the NICU was
      obtained by hospital database. Vaccination status of each subject at 24 months of
      chronological age was acquired by the Apulian Regional Vaccination Register
      (GIAVA). 159 preterm borns were enrolled in this study. 98.1% received the 1st
      dose of hexavalent vaccine and 98.7% the 1st dose of pneumococcal conjugate
      vaccine. The 8.8% of hexavalent vaccinations were performed during
      hospitalization. The percentage of immunized subjects decreased to 91.2% and
      87.3% for the 2nd and 3rd dose of hexavalent vaccine and to 90.6% and 86.1% for
      the 2nd and 3rd dose of pneumococcal conjugate vaccine. Coverage for MMR, MEN C
      and Varicella vaccines were, respectively 76.4%, 86.0% and 80.9%. Pre-terms
      received the vaccinations later than the age recommended by public health
      guidelines. Age at the immunization, for all vaccines, seems to increase for
      lower gestational age and birth weight and for higher length of hospitalization.
      This study shows a high risk of vaccine delay among pre-terms born. There is a
      strong need to improve specific vaccination strategies for this group.
      Neonatologists might play a key role in informing parents about the vaccination
      schedule at the moment of NICU discharge and during follow-up, also preparing
      correct time schedule.

PMID- 29351056
TI  - Remediation of Radiation-Induced Cognitive Dysfunction through Oral
      Administration of the Neuroprotective Compound NSI-189.
AB  - Clinical management of primary and secondary central nervous system (CNS)
      malignancies frequently includes radiotherapy to forestall tumor growth and
      recurrence after surgical resection. While cranial radiotherapy remains
      beneficial, adult and pediatric brain tumor survivors suffer from a wide range of
      debilitating and progressive cognitive deficits. Although this has been
      recognized as a significant problem for decades, there remains no clinical
      recourse for the unintended neurocognitive sequelae associated with these types
      of cancer treatments. In previous work, multiple mechanisms have been identified
      that contribute to radiation-induced cognitive dysfunction, including the
      inhibition of neurogenesis caused by the depletion of radiosensitive populations
      of stem and progenitor cells in the hippocampus. To explore the potential
      neuroprotective properties of a pro-neurogenic compound NSI-189, Long-Evans rats
      were subjected to a clinically relevant fractionated irradiation protocol
      followed by four weeks of NSI-189 administered daily by oral gavage. Animals were
      then subjected to five different behavioral tasks followed by an analysis of
      neurogenesis, hippocampal volume and neuroinflammation. Irradiated cohorts
      manifested significant behavioral decrements on all four spontaneous exploration
      tasks. Importantly, NSI-189 treatment resulted in significantly improved
      performance in four of these tasks: novel place recognition, novel object
      recognition, object in place and temporal order. In addition, there was a trend
      of improved performance in the contextual phase of the fear conditioning task.
      Importantly, enhanced cognition in the NSI-189-treated cohort was found to
      persist one month after the cessation of drug treatment. These neurocognitive
      benefits of NSI-189 coincided with a significant increase in neurogenesis and a
      significant decrease in the numbers of activated microglia compared to the
      irradiated cohort that was given vehicle alone. The foregoing changes were not
      accompanied by major changes in hippocampal volume. These data demonstrate that
      oral administration of a pro-neurogenic compound exhibiting anti-inflammatory
      indications could impart long-term neurocognitive benefits in the irradiated
      brain.

PMID- 29351057
TI  - Global Gene Expression Response in Mouse Models of DNA Repair Deficiency after
      Gamma Irradiation.
AB  - In the event of an improvised nuclear device or "dirty bomb" in a highly
      populated area, potentially hundreds of thousands of people will require
      screening to ensure that exposed individuals receive appropriate treatment. For
      this reason, there is a need to develop tools for high-throughput radiation
      biodosimetry. Gene expression represents an emerging approach to biodosimetry and
      could potentially provide an estimate of both absorbed dose and individual
      radiation-induced injury. Since approximately 2-4% of humans are thought to be
      radiosensitive, and would suffer greater radiological injury at a given dose than
      members of the general population, it is of interest to explore the potential
      impact of such sensitivity on the biodosimetric gene expression signatures being
      developed. In this study, we used wild-type mice and genetically engineered mouse
      models deficient in two DNA repair pathways that can contribute to radiation
      sensitivity to estimate the maximum effect of differences in radiosensitivity. We
      compared gene expression in response to a roughly equitoxic (LD50/30) dose of
      gamma rays in wild-type C57BL/6 (8 Gy) and DNA double-strand break repair
      deficient Atm-/- (4 Gy) and Prkdcscid (3 Gy) mutants of C57BL/6. Overall, 780
      genes were significantly differentially expressed in wild-type mice one day
      postirradiation, 232 in Atm-/- and 269 in Prkdcscid. Upstream regulators
      including TP53 and NFkappaB were predicted to be activated by radiation exposure
      in the wild-type mice, but not in either of the DNA repair-deficient mutant
      strains. There was also a significant muting of the apparent inflammatory
      response triggered by radiation in both mutant strains. These differences
      impacted the ability of gene expression signatures developed in wild-type mice to
      detect potentially fatal radiation exposure in the DNA repair-deficient mice,
      with the greatest impact on Atm-/- mice. However, the inclusion of mutant mice in
      gene selection vastly improved performance of the classifiers.

PMID- 29351059
TI  - Nematode Thelazia callipaeda is spreading across Europe. The first survey of red
      foxes from Slovakia.
AB  - Canine thalaziosis caused by the spirurid nematode Thelazia callipaeda has
      started to spread across Western and Central Europe during the last decade. In
      Slovakia, the first autochthonous cases of this infection were recorded in 2016
      in four dogs from the south-eastern part of the country. In August 2017 other
      autochthonous case, again from the same locality, was reported. Seeing that red
      foxes are considered the main reservoir hosts for T. callipaeda, their
      examination could provide an integrated view of the real parasite distribution.
      Within the present study, 523 red foxes were examined by necropsy, and T.
      callipaeda nematodes were recovered from the conjunctival sacs of 7 animals,
      which represents an overall positivity of 1.3%. Six infected foxes originated in
      eastern Slovakia, which is consistent with the area where positive dogs were
      recently found. Also, single positive red fox was found in north-western
      Slovakia. Regarding morphology and morphometry, the specimens recovered from the
      foxes in this study were evaluated as larger in size when compared to nematodes
      isolated from Slovak dogs as well as dogs and foxes from other studies. BLAST
      analyses of the cox1 gene showed that all specimens isolated from Slovak red
      foxes were identified as haplotype 1 which circulated also in other European
      countries. Considering that majority of the infected animals, dogs and foxes,
      came from Kosice region, we can presume that this area might become endemic in a
      short period of time.

PMID- 29351060
TI  - Nematode parasites of Duttaphrynus stomaticus (Lutken, 1864) (Amphibia: Anura)
      with description of a new species of Rhabdias Stiles and Hassall, 1905 (Nematoda:
      Rhabdiasidae) from Dehradun (Uttarakhand), India.
AB  - Rhabdias stomatica sp. nov. from the lungs of Duttaphrynus stomaticus (Lutken,
      1864) from Dehradun, Uttarakhand, India is described and illustrated. Rhabdias
      stomatica sp. nov. is the 16th species described from the Oriental
      biogeographical region and the 8th species from India. The new species is
      differentiated from the closely related Oriental species in having 4 weakly
      developed lips, a trapezoidal shaped buccal cavity, different position of nerve
      ring and in the esophagus/body length ratio. In addition, to the new species
      found in the lungs, mature specimens of Aplectana macintoshii (Stewart, 1914)
      Travassos, 1931 and larvae representing two unidentified species of nematode were
      found in the large intestine of the D. stomaticus.

PMID- 29351058
TI  - Development and Characterization of an In Vitro Model for Radiation-Induced
      Fibrosis.
AB  - Radiation-induced fibrosis (RIF) is a major side effect of radiotherapy in cancer
      patients with no effective therapeutic options. RIF involves excess deposition
      and aberrant remodeling of the extracellular matrix (ECM) leading to stiffness in
      tissues and organ failure. Development of preclinical models of RIF is crucial to
      elucidate the molecular mechanisms regulating fibrosis and to develop therapeutic
      approaches. In addition to radiation, the main molecular perpetrators of fibrotic
      reactions are cytokines, including transforming growth factor-beta (TGF-beta). We
      hypothesized that human oral fibroblasts would develop an in vitro fibrotic
      reaction in response to radiation and TGF-beta. We demonstrate here that
      fibroblasts exposed to radiation followed by TGF-beta exhibit a fibrotic
      phenotype with increased collagen deposition, cell proliferation, migration and
      invasion. In this in vitro model of RIF (RIFiv), the early biological processes
      involved in fibrosis are demonstrated, along with increased levels of several
      molecules including collagen 1alpha1, collagen XIalpha1, integrin-alpha2 and
      cyclin D1 mRNA in irradiated cells. A clinically relevant antifibrotic agent,
      pentoxifylline, and a curcumin analogue both mitigated collagen deposition in
      irradiated fibroblast cultures. In summary, we have established an in vitro model
      for RIF that facilitates the elucidation of molecular mechanisms in radiation
      induced fibrosis and the development of effective therapeutic approaches.

PMID- 29351061
TI  - The first case of Leporacarus gibbus infestation in a rabbit from Poland.
AB  - This case report presents asymptomatic infestation with Leporacarus gibbus
      (formerly Listrophorus gibbus) in a pet rabbit. This is the first report of L.
      gibbus infestation in a pet rabbit from Poland. Previously, infestation in Poland
      had been detected only in hares.

PMID- 29351062
TI  - Phylogeny and cocoon production in the parasitic leech Myzobdella lugubris Leidy,
      1851 (Hirudinidae, Piscicolidae).
AB  - Myzobdella lugubris is a commensal leech on crustaceans and a parasite to fishes,
      surviving predominantly in brackish waters throughout North America. Specimens in
      this study were collected within the tidal zone of the Delaware River basin (New
      Jersey and Pennsylvania). To compare regional M. lugubris specimens, defined
      characters were scored after dorsal and ventral dissections, and phylogenetic
      relationships were resolved using cytochrome c oxidase subunit 1 (CO1), 12S
      ribosomal RNA (rDNA) and 18S rDNA gene fragments. Variance between regional
      populations was low, suggesting recent dispersal events and/or strong
      evolutionary constraints. The reproductive biology of M. lugubris was explored by
      quantitative analysis of secreted cocoons. Specimens produced 32.67 +/- 4.50
      cocoons with fertilization ratios of 88.1% and hatching times of 48 +/- 7 days at
      17 degrees C under laboratory conditions. At 22 degrees C, 46 +/- 28 cocoons were
      produced with fertilization ratios of 70.27% and hatching times of 28 +/- 5 days.
      Surprisingly, each cocoon supported only one embryo, which is unusual among
      oligochaetes.

PMID- 29351063
TI  - Morphological and molecular characterization of Seuratascaris numidica (Seurat,
      1917) (Ascaridida: Ascarididae).
AB  - Seuratascaris numidica (Seurat, 1917) is a specialized nematode species
      parasitizing amphibians only. In the present study, the detailed morphology of
      this poorly known species was studied using light and scanning electron
      microscopy based on the newly material collected from Hoplobatrachus chinensis
      (Osbeck) (Amphibia: Anura) in China. We found that the relative length of
      intestinal caecum in our male specimens (representing 68.4-71.1% of oesophageal
      length) is slighter longer than the previously reported data (not over 60.0% of
      oesophageal length). Our SEM observations also revealed the presence of ca. 64-76
      small conical denticles on each lip. In addition, Angusticaecum wuyiensis Wang,
      1981, collected from Rana schmackeri Boettger (Amphibia: Anura) from Wuyi
      Mountain in Fujian Province, China was considered as a new synonym of S.
      numidica. The ITS and cox1 sequences of S. numidica were also sequenced for the
      first time and there is no nucleotide variability detected in both regions. The
      present supplementary morphological and molecular data (especially the ITS and
      cox1 sequences) obtained herein is extremely important and useful to determine
      the morphological variability, population genetics and phylogenetic position of
      S. numidica in the future.

PMID- 29351064
TI  - Molecular target analysis of stearoyl-CoA desaturase genes of protozoan
      parasites.
AB  - Protozoan parasites can synthesize polyunsaturated fatty acids. They possess
      stearoyl-CoA desaturase to convert stearate into oleate and linoleate. Stearoyl
      CoA desaturase are the key enzymes required for the synthesis of unsaturated
      fatty acids. It seems attractive to evaluate the possibility of using unsaturated
      fatty acid biosynthesis pathways as drug targets. In this study, the authors
      investigate codon usage bias, base composition variations and protein sequence in
      ten available complete stearoyl-CoA desaturase gene sequences from Toxoplasma
      gondii, Neospora caninum etc. The results show that fatty acid desaturase genes
      GC content high of parasitic protozoa genes, GC content up to 63.37%, while fatty
      acid desaturase genes of parasitic protozoa prefers to use codon ending with G/C.
      In addition, the expected curve was also drawn to reveal the relationship of ENC
      and GC3s when the codon usage was only subjected to the nucleotide composition
      constraint. The genes lied on the expected curve in ENC-plot, indicating
      nucleotide composition constraint played a role in the condon usage pattern.
      Protein analysis, we find that all proteins are stearoyl-CoA desaturase, have
      sites of iron-binding active centers and contain three conserved His-rich motifs.
      If stearoyl-CoA desaturase is unusual to these parasites, it provides basis as a
      promising target for the development of selective chemical intervention.
      Therefore, the Bioinformatics analysis of protein and codon can help improve the
      work of genetic engineering and drug screening.

PMID- 29351065
TI  - Measurement of binding strength between prey proteins interacting with Toxoplasma
      gondii SAG1 and SAG2 using isothermal titration calorimetry (ITC).
AB  - Following the outcome from a previously performed yeast two-hybrid experiment,
      the binding strength between T. gondii SAG1 and SAG2 and their respective prey
      proteins were further confirmed in this study. The sag1, sag2 and their prey
      genes were amplified and cloned into a pGEMT vector. To express the recombinant
      proteins, the fragments were then subcloned into a pRSETA vector and transformed
      into E. coli BL21 (DE3) cells. The recombinant proteins were expressed optimally
      at 37 degrees C and 1mM of IPTG. The 6X His-tag fusion proteins were purified,
      dialyzed and concentrated. To confirm the expressed proteins, the recombinant
      proteins were analysed by SDS-PAGE and Western blot. As expected, the size of
      SAG1, SAG2, HLY and HZF protein were 32, 23, 28 and 37 kDa, respectively. The
      purified proteins were loaded onto a MicroCal Auto-iTC200 calorimeter from
      MicroCalTM to quantify binding strength. ITC results indicated there was a
      typical binding curve for interactions between SAG1 and HLY protein. However,
      there was an atypical binding curve obtained for interactions between SAG2 and
      HZF protein. By observing the data obtained from the ITC assay, both of the human
      proteins (HLY and HZF) were demonstrated to bind to their respective SAG1 and
      SAG2 proteins.

PMID- 29351066
TI  - Contamination of swimming pools and hot tubs biofilms with Acanthamoeba.
AB  - The members of Acanthamoeba genus are ubiquitous amoeba which could be a
      pathogenic parasite. The amoeba is resistant to the common chlorine concentration
      that used for disinfecting the swimming pool water. Therefore, the pools can be
      suitable environments for the survival and multiplication of the amoeba. In this
      cross sectional study, 10 indoor recreational water centers from different
      regions of Tabriz city were selected and sampling was done from fixed and
      floating biofilms of the swimming pools and hot tubs. The samples were cultured
      and monitored for the presence of amoeba cyst or trophozoite. For molecular
      identification of Acanthamoeba, PCR (polymerase chain reaction) and sequencing
      were conducted based on genus specific fragment of 18S ribosomal DNA (Rns).
      Acanthamoeba contamination was observed in 6 centers of 10 recreational centers.
      Based on the amoeba isolation from fixed and floating biofilms, 2 (20%) swimming
      pools, and 5 (50%) hot tubs were contaminated. Based on the type of the sample,
      the highest contamination was found in the hot tub water (40%) and the least was
      found in the swimming pools water (10%) and fixed biofilms of the swimming pools
      (10%). Out of 8 isolates, 5 (62.5%) were shown expected product in PCR
      amplification. Sequence analysis showed that Acanthamoeba isolates belonged to
      the T3 and T4 genotypes. The study revealed a high degree of contamination in the
      indoor recreational water centers in Tabriz city. So, it is essential to pay
      closer attention to the hygiene of swimming pools and hot tubs.

PMID- 29351067
TI  - Changes in the incidence of intestinal giardiosis in Mexican population during
      five years (2011-2015).
AB  - Giardiosis is a parasitic disease caused by the protozoan Giardia intestinalis,
      which is distributed worldwide. Most of the data on the prevalence of giardiosis
      in Mexico comes from research, but it is also necessary to study the data
      provided by the Mexican Health Ministry and issued by the General Directorate of
      Epidemiology. The aim of this work was analyse the national surveillance data for
      human giardiosis in order to update the epidemiological data of this disease in
      Mexico. A retrospective observational analysis of giardiosis (from January 2011
      to December 2015) was performed in the annual reports emitted by the GDE in
      Mexico. The cases were classified by year, state, age group, gender and seasons
      of the year. During the period of 2011-2015, a reduction of 38.51% was observed
      in the total number of new cases of giardiosis reported in the whole country The
      states of Sinaloa, Yucatan, and Chiapas presented the highest number of new cases
      reported during the analysed period. Giardiosis rates were always higher among
      women in all age groups, but the maximum incidence was observed in both sexes in
      the age group of 1-4 years old (the most susceptible group). On the other hand,
      the number of cases increased dramatically in southern states during warmer
      months. Giardiosis is influenced by ambient temperature changes along the year,
      although this study suggests that tends to decrease in all the analysed states
      and could be related to the overall improvement of hygienic practices within the
      Mexican population.

PMID- 29351068
TI  - A new species of Aplectana (Nematoda, Cosmocercidae) in Goniurosaurus
      bawanglingensis (Squamata, Eublepharidae), from Hainan Province, China.
AB  - Aplectana hainanensis sp. nov. (Ascaridida, Cosmocercidae) from the intestines of
      Goniurosaurus bawanglingensis (Squamata, Eublepharidae) is described and
      illustrated. Aplectana hainanensis sp. nov. represents the 52nd species assigned
      to the genus and the 5th species reported from the Sino-Japanese region. It is
      easily separated from the 4 species previously reported from the region by the
      distribution pattern of male caudal papillae: A. macintoshii has an irregular
      pattern; A. hylae has no precloacal papillae; A. fujianae has 1 pair of
      precloacal papillae; A paucipapillosa has 3 pairs of precloacal papillae;
      Aplectana hainanensis sp. nov. has 7 pairs of precloacal papillae.

PMID- 29351069
TI  - Metazoan parasite fauna of migrating common garfish, Belone belone (L.), in the
      Baltic Sea.
AB  - A total of 35 common garfish, Belone belone (Linnaeus, 1761), were studied for
      metazoan parasites on their spawning grounds in the western Baltic Sea. Nine
      parasite species were found, and six new locality records could be established
      for German coastal waters (Axine belones, Monogenea; Proteocephalus sp., Cestoda;
      Anisakis simplex (s.s.), Contracaecum rudolphii A and Hysterothylacium aduncum,
      Nematoda; Echinorhynchus gadi, Acanthocephala). For the first time, the marine
      ectoparasite A. belones was recorded from the gills of garfish inside the Baltic
      Sea, indicating its ability to survive the spawning migration as well as the
      brackish water conditions at its reproduction grounds. This is alike the
      endohelminth A. simplex (s.s.), that was identified by molecular analyses of the
      internal transcribed spacer (ITS-1, 5.8S, ITS-2) region. Almost all isolated
      metazoans were parasites commonly recorded from the northeast Atlantic Ocean and
      the North Sea. The lower number of typical generalist Baltic Sea parasites
      indicates the rapid migration of common garfish onto the spawning grounds,
      reducing the access and uptake of these species.

PMID- 29351070
TI  - A serological study of antibodies to Anaplasma phagocytophilum and Borrelia
      burgdorferi sensu lato in the sera of healthy individuals collected two decades
      apart.
AB  - Sera collected from healthy individuals from the general population in the Czech
      Republic during repeated cross-sectional surveys were analyzed. Samples collected
      in the same six districts in two time periods, 1978-1989 and 2001, were compared.
      The study subjects were divided into six age categories between 10 and 59 years.
      Overall, 434 samples from 1978-1989 and 270 samples from 2001 were screened for
      Anaplasma phagocytophilum (AP) and Borrelia burgdorferi sensu lato (BB). The anti
      AP positivity rates were 13.1% and 11.5% in the first and second period,
      respectively, and did not differ significantly between the periods (P = 0.559).
      The anti-BB antibodies were detected in 33.9% and 14.8% of study subjects,
      respectively. The positivity rates were significantly lower in the second period
      (P<0.001). No considerable changes were observed in the sex distribution of
      positive findings between the two periods. The highest positivity rates of anti
      AP antibodies were found in the 10-14 year age group: 16.0% in 1978-1989 and
      16.7% in 2001. The age distribution of the anti-AP antibody positivity rates did
      not change substantially (P = 0.872). In 1978-1989, the lowest anti-BB antibody
      positivity rate (26.7%) was found in the 10-14 year age group, with a gradual
      increase with age to 41.1% in 50-59 year-olds. In 2001, the positivity rate in
      the 10-14 year age group was 26.2% and was not significantly different from that
      in the first period (P = 0.955). However, the positivity rates in the older age
      groups 15-59 years decreased significantly (P<0.001) and varied between 8.3% and
      15.1%.

PMID- 29351071
TI  - A frequent roundworm Baylisascaris transfuga in overpopulated brown bears (Ursus
      arctos) in Slovakia: a problem worthy of attention.
AB  - The genus Baylisascaris (order Ascaridida) includes numerous relatively host
      specific nematodes, which are common in intestines of wild mammals. Some of them
      may have impact on veterinary and public health, as their larvae have the
      potential to cause visceral, ocular, and/or neural larva migrans in a wide range
      of mammals, birds, and humans. Baylisascaris transfuga is a parasite occurring in
      a range of bear species throughout the world. We present the current data on B.
      transfuga occurrence in brown bears from a relatively restricted territory of the
      Polana Protected Landscape Area in Central Slovakia, obtained by traditional
      methods (faecal examination, morphology). Species affiliation was confirmed by
      employing molecular markers generating nuclear 28S and mitochondrial cox1
      sequences in adult worms. Based on 17 examined samples (15 excrements and two
      intestines of young bear females), the occurrence of B. transfuga in the surveyed
      area was assessed as 52.9%. Both bear females were infected with adult and
      juvenile worms. Due to the high density of bears in the locality, the high
      infection rate with ascarids, and the huge number of eggs produced by the
      parasites, it is apparent that the respective environment, including the
      inhabited areas, might be markedly contaminated by Baylisascaris eggs. The
      ability of B. transfuga to serve as a zoonotic agent has not been unambiguously
      proved; however, this attribute should be considered and subjected to further
      research.

PMID- 29351072
TI  - Scanning electron microscopy study of Strabax monstrosus von Nordmann, 1864
      (Copepoda: Chondracanthidae) from Tunisian waters and histopathological study of
      its effects on host.
AB  - Strabax monstrosus von Nordmann, 1864 (Copepoda: Chondracanthidae) is an
      ectoparasite and it was recently recorded from small red scorpionfish, Scorpaena
      notata Rafinesque, and red scorpionfish, Scorpaena scrofa L., collected from
      Tunisian coastal waters. Copepod females were found deeply embedded in the
      branchial cavity reaching the cardiac region with their mouth-parts. Observations
      of females and males using scanning electron microscopy showed a number of
      morphological features that have been previously overlooked or incompletely
      presented. In this study, we report for the first time the fine structures of
      appendages, mouthparts, external genital organs (nuptial organs), and other
      structures of male and female Strabax monstrosus. Histopathological study showed
      lesions in the cardiac region of the host fish which is the target site of the
      parasite. The presently reported finding is the first record of Strabax
      monstrosus from Scorpaena notata and Scorpaena scrofa collected from Tunisian
      waters.

PMID- 29351073
TI  - Molecular and serological investigation of infectious diseases in captive and
      free-range crab-eating fox (Cerdocyon thous - Linnaeus, 1776) from northeastern
      Brazil.
AB  - The aim of this study was to detect DNA and antibodies anti-Leishmania spp.,
      Neospora caninum and Toxoplasma gondii in captive and free-range crab-eating fox
      (Cerdocyon thous) from northeastern Brazil. Twenty-five crab-eating foxes from
      different states of northeastern Brazil were sampled by this study. Blood samples
      were collected by cephalic or jugular vein punctures. The whole blood was
      submitted to PCR, and the sera samples to the serological analysis as follows:
      MAT for T. gondii, NAT for N. caninum, and ELISA for L. chagasi. The frequence of
      antibodies anti-T. gondii was 50% and 29.41% for free-range and captive wild
      canids, respectively. The frequence of antibodies anti-N. caninum observed by
      this study was 62.50% and 23.52% for free-range and captive wild canids,
      respectively. The frequence of antibodies anti-L. chagasi was 4.0% for captive
      wild canids. Co-infections cases were identified as follows: one captive wild
      canid seropositive for T. gondii and L. chagasi and two free-range animals
      seropositive for T. gondii and N. caninum. All PCR assays performed were negative
      for the pathogens analyzed. This study describes the presence of antibodies anti
      T. gondii, N. caninum e L. chagasi in wild canids from northeastern Brazil and
      highlights the necessity of further studies on infectious diseases in free-range
      and captive wild canids.

PMID- 29351074
TI  - Two nematode species from freshwater and marine fishes in Thailand, including
      Ascarophis scatophagi sp. nov. (Cystidicolidae) from Scatophagus argus
      (Scatophagidae).
AB  - One new and one known species of parasitic nematodes are reported from Thailand
      for the first time: Falcaustra kaverii (Karve et Naik,1951) (Kathlaniidae) from
      the intestine of the freshwater fish Poropuntius deauratus (Valenciennes)
      (Cyprinidae) (new host record) and Ascarophis scatophagi sp. nov.
      (Cystidicolidae) from the intestine of the marine fish Scatophagus argus
      (Linnaeus) (Scatophagidae). The morphology of both these species was studied with
      the use of light (LM) and scanning electron microscopy (SEM) (the latter method
      used for F. kaverii for the first time). The new species (A. scatophagi) is
      mainly characterized by nonfilamented, markedly elongate-oval eggs (size 42-45 *
      18 MUm), spicules 555-642 MUm and 105-150 MUm long, the muscular/glandular
      oesophagus length ratio (1:13-34), bifurcate deirids, the length of the female
      tail (159-249 MUm) and cephalic structures typical of the nominotypical subgenus
      Ascarophis. Representatives of Falcaustra Lane, 1915 and Ascarophis van Beneden,
      1871 were not previously reported from fishes in Thai waters.

PMID- 29351075
TI  - Pathological and molecular studies of the renal trematode Paratanaisia bragai in
      Indian peafowls (Pavo cristatus).
AB  - Endoparasitic diseases are commonly encountered in free-ranging birds. Although
      not all endoparasites cause disease, persistent infection with large numbers of
      parasites almost always affects normal physiological functions, leading to
      deleterious effects on the host. This paper describes the anatomopathological
      alterations caused by the renal trematode Paratanaisia bragai in Indian peafowl
      (n = 3) and examines the phylogeny of these and related parasites. Peafowl from
      forests in and around the Bareilly region, Uttar Pradesh, India, were necropsied,
      and microscopic and molecular investigations were performed. The peafowl were
      confirmed to be infected with P. bragai. Significant gross pathological lesions
      suggested nephrosis, and microscopic findings indicated a mild-to-moderate degree
      of nephrosis caused by the parasites in the tissue. The parasites were identified
      as P. bragai by histomorphological analysis of adult and eggs in the ureters, and
      the identification was confirmed by PCR and phylogenetic analysis. Nucleotide
      sequencing of the PCR products from the renal trematodes recovered from Indian
      peafowl revealed a close association with P. bragai from Columbiformes in the
      United Kingdom and Spain. The pathology and molecular epidemiology of parasitic
      diseases affecting peafowl is not well understood in India. This is the first
      report from India and the second report worldwide to document P. bragai infection
      in peafowl.

PMID- 29351076
TI  - Parasites in stray dogs from Italy: prevalence, risk factors and management
      concerns.
AB  - Parasites are among the most common pathogens recorded in dogs. High prevalence
      rates are usually reported in stray and shelter dogs, as these animals are less
      likely to be tested and treated. In this study a survey was carried out on
      intestinal and lung parasites of stray dogs at the moment of the admission in a
      shelter in Central Italy. In the period June 2014-June 2015, 262 individual
      faecal samples were examined. Twelve parasitic taxa were detected. Helminths were
      more prevalent than protozoa (61.8% and 25.6%, respectively). Ancylostomatidae
      showed the higher prevalence (40.5%), followed by Giardia duodenalis (21.4%),
      Toxocara canis (20.6%) and Trichuris vulpis (17.6%). Angiostrongylus vasorum was
      the most prevalent lungworm (12.6%), Crenosoma vulpis being recorded just in one
      dog. G. duodenalis had a high prevalence, probably because of the diagnostic
      techniques adopted, actually the most sensitive available for its detection.
      Nevertheless, the zoonotic potential of this parasite in dogs appears reduced, as
      all the isolates were identified as C (24.0%) and D (76.0%) dog specific
      assemblages. Taeniidae constituted a high potential zoonotic risk, as from the
      eggs it is impossible to exclude they were Echinococcus granulosus, the most
      relevant zoonotic parasite in Europe. The present study underline the importance
      of stray dogs control, aimed at preventing or minimizing parasitic spread and
      zoonotic transmission.

PMID- 29351077
TI  - Molecular and morphological characterisation of Rhabdias picardiae Junker,
      Lhermitte-Vallarino et Bain, 2010 (Nematoda: Rhabdiasidae) from Delaland's River
      Frog, Amietia delalandii (Dumeril et Bibron, 1841) (Amphibia: Pyxicephalidae) in
      South Africa.
AB  - Rhabdias picardiae previously known from the Guttural Toad, Sclerophrys
      gutturalis (Bufonidae) is described from a new host, Delaland's River Frog,
      Amietia delalandii (Pyxicephalidae). The species identification is confirmed by
      analysis of the COI gene sequence and morphological comparison with the original
      description. Morphological details of apical structures in adult parasitic R.
      picardiae, namely, the shape and position of lips, the number and position of
      external labial papillae, and the buccal capsule morphology are described using
      light and scanning electron microscopy. The buccal capsule width and length, the
      distance from anterior end to nerve ring and excretory pore, and ratios of
      distance to vulva to body length and body length to width were identified as less
      variable metrical characters in the studied sample of 30 specimens. Adult
      specimens demonstrated differences in the position of lips in relation to the
      oral opening and position of the buccal capsule in relation to the oesophagus
      depending on the size (age) of worms. The infective larvae of R. picardiae are
      described for the first time and characterised by two lateral alae consisting of
      two ridges, triangular pseudolabia with rounded tops, and presence of
      ornamentation on the rounded tail tip.

PMID- 29351078
TI  - Asymmetric peptidomimetics containing L-tartaric acid core inhibit the aspartyl
      peptidase activity and growth of Leishmania amazonensis promastigotes.
AB  - Aspartyl-type peptidases are promising chemotherapeutic targets in protozoan
      parasites. In the present work, we identified an aspartyl peptidase activity from
      the soluble extract of Leishmania amazonensis promastigotes, which cleaved the
      fluorogenic peptide 7-methoxycoumarin-4-acetyl-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg
      Leu-Lys(DNP)-D-Arg-amide (cathepsin D substrate) under acidic pH conditions at 37
      degrees C, showing a KM of 0.58 MUM and Vmax of 129.87 fluorescence arbitrary
      units/s mg protein. The leishmanial aspartyl peptidase activity was blocked by
      pepstatin A (IC50 = 6.8 MUM) and diazo-acetyl-norleucinemetilester (IC50 = 10.2
      MUM), two classical aspartyl peptidase inhibitors. Subsequently, the effects of 6
      asymmetric peptidomimetics, containing L-tartaric acid core, were tested on both
      aspartyl peptidase and growth of L. amazonensis promastigotes. The
      peptidomimetics named 88, 154 and 158 promoted a reduction of 50% on the
      leishmanial aspartyl peptidase activity at concentrations ranging from 40 to 85
      MUM, whereas the peptidomimetic 157 was by far the most effective, presenting
      IC50 of 0.04 MUM. Furthermore, the peptidomimetics 157 and 154 reduced the
      parasite proliferation in a dose-dependent manner, displaying IC50 values of 33.7
      and 44.5 MUM, respectively. Collectively, the peptidomimetic 157 was the most
      efficient compound able to arrest both aspartyl peptidase activity and
      leishmanial proliferation, which raises excellent perspectives regarding its use
      against this human pathogenic protozoan.

PMID- 29351079
TI  - Syphacia muris infection in rats attenuates colorectal carcinogenesis through
      oxidative stress and gene expression alterations. Implications for modulatory
      effects by Bryostatin-1.
AB  - Accumulating evidence suggest that some infectious agents may interfere in the
      natural progression of neoplasia. This study examined the association between
      chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine
      (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable
      therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan,
      Bugulane ritina, was investigated against this combined effect.DMH administration
      has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal
      carcinogenesis, while the S. muris infection combined with DMH has significantly
      increased the total numbers of ACF. Nonetheless, treatment with Bryostatin-1
      after infection has significantly reduced the ACF numbers particularly larger
      ones. This inhibition was concomitant with significant inhibition in the
      immunohistochemical levels of the ki67, Caspase-3 and IgM levels in colorectal
      epithelium, as well as serum levels of IgM and IgG. Additionally, treatment with
      Bryostatin-1 after S. muris + DMH has modulated enzymatic antioxidative markers
      levels of superoxide dismutase and catalase as well as the non-enzymatic
      antioxidant markers levels of reduced glutathione, lipid peroxidation, nitric
      oxide and total antioxidant capacity. Further, treatment with Bryostatin-1 has
      down-regulated the mRNA expression levels of COX-2 and APC genes in colorectal
      mucosa. In conclusion, infection with S. muris during colorectal carcinogenesis
      has significantly modulated the oxidative stress markers in the colorectum, while
      treatment with Bryostatin-1 has exerted significant curative potential. A
      mechanism could be explained that Bryostatin-1 treatment has reduced oxidative
      stress markers activities along with affecting host to parasite immunity possibly
      leading to changes in the COX-2 and APC expression, retarding cellular
      proliferation and subsequently reducing the colorectal carcinogenesis events.

PMID- 29351080
TI  - Ultrastructure of digenean trematode eggs (Platyhelminthes: Neoophora): A review
      emphasizing new comparative data on four European Microphalloidea.
AB  - Despite their tremendous diversity and their medical and veterinary importance,
      details of egg ultrastructure among the digenean trematodes has been studied
      rather little. The available literature is spread over several decades and
      several species, but has not been adequately reviewed to reveal patterns of
      similarity and divergence. We present this review to synthesize and analyse what
      is known from the available literature reporting studies using both transmission
      electron microscopy (TEM) and scanning electron microscopy (SEM). To support our
      general review of existing literature, we also have synthesized our own
      previously published descriptions, and present herein our new previously
      unpublished data. From these new electron micrographs, we provide a comparative
      analysis of the intrauterine eggs of four digenean species, representing four
      genera and three families of the superfamily Microphalloidea, collected from four
      different host wildlife species in four European countries: 1) Mediogonimus
      jourdanei (Prosthogonimidae) from Myodes glareolus (Mammalia: Rodentia),
      collected in France; 2) Maritrema feliui (Microphallidae) from Crocidura russula
      (Mammalia: Soricimorpha), collected in Spain; 3) Brandesia turgida
      (Pleurogenidae) from Pelophylax ridibundus (Amphibia: Anura: Ranidae), collected
      in Russia; and 4) Prosotocus confusus (Pleurogenidae) from Rana lessonae
      (Amphibia: Anura: Ranidae), collected in Belarus. All were studied by preparing
      whole worms by various techniques for TEM, so that eggs could be studied in situ
      within the uterus of the parent worm. Based on the literature review and the new
      data presented here, we describe basic similarities in patterns of embryogenesis
      and egg formation among all trematode species, but substantial variations in
      timing of larvigenesis, sculpturing of egg shell surfaces, and some other
      features, especially including accessory cocoon coverings outside the egg shells
      of B. turgida and P. confusus. In the future, many more studies are needed to
      explore egg ultrastructure in other digenean taxa, to explore potential
      phylogenetic patterns in egg development and structure, and to correlate
      structure with function in the life cycle.

PMID- 29351081
TI  - Characterization of phosphate transporter(s) and understanding their role in
      Leishmania donovani parasite.
AB  - Inorganic phosphate (Pi) is shown to be involved in excretion of methylglyoxal
      (MG) in the promastigote form of Leishmania donovani parasite. Absence of Pi
      leads to its accumulation inside the parasite. Accumulation of MG is toxic to the
      parasite and utilizes glyoxylase as well as excretory pathways for its
      detoxification. In addition, Pi is also reported to regulate activities of
      ectoenzymes and energy metabolism (glucose to pyruvate) etc. Thus, it is known to
      cumulatively affect the growth of Leishmania parasite. Hence the transporters,
      which allow the movement of Pi across the membrane, can prove to be a crucial
      drug target. Therefore, we characterized two phosphate transporters in Leishmania
      (i) H+ dependent myo-inositol transporter (LdPHO84), and (ii) Na+ dependent
      transporter (LdPHO89), based on similar studies done previously on other lower
      organisms and trypanosomatids. We tried to understand the secondary structure of
      these two proteins and confirm modulation in their expression with the change in
      Pi concentration outside. Moreover, their modes of action were also measured in
      the presence of specific inhibitors (LiF, CCCP). Further analysis on the
      physiological role of these transporters in various stages of the parasite life
      cycle needs to be entrenched.

PMID- 29351082
TI  - Prevalence of endoparasitic infections of birds in zoo gardens in Serbia.
AB  - This report represents the prevalence of endoparasitic infections of birds in
      zoological gardens in Serbia. Coprological examination conducted during 2015 and
      2016, involved samples from 318 individual birds belonging to 112 species, in
      three zoo gardens (Belgrade, Palic and Bor). Individual faeces samples were
      analysed by the flotation method in salt solution. The presence of endoparasites
      was established in 51.96% (Belgrade), 46.16% (Palic) and 16.66% (Bor) of the
      tested birds. We diagnosed coccidian oocysts, eggs of Capillaria spp, Heterakis
      spp, Trichostrongylus spp, Ascaridia spp, Syngamus trachea and eggs of yet
      unidentified trematode. There were no detection of parasites from the class of
      cestodes. Prevalence of infection with coccidia, depending on location, was in
      the ranges between 8.33% and 32.84%, capillariosis 2.77% and 29.41%, heterakiosis
      2.56% and 12.74%, trichostrongylidosis 5.55% and 25.64%, askaridiosis 10.25% and
      10.78%, syngamosis 2.94% and trematodes of unknown etiology 2.45%. Coinfections
      with two or three parasitic species were detected in Belgrade and Palic Zoo
      Gardens, while quadruple infection was established in birds of Belgrade Zoo
      Garden. Obtained results can be used in establishing programs for health
      protection of endangered bird species.

PMID- 29351083
TI  - Transcriptional analysis of immune-relevant genes in the mucus of Labeo rohita,
      experimentally infected with Argulus siamensis.
AB  - The knowledge of mucosa-associated molecular events that occur during infections
      is scarce despite the well-established importance of mucus in fish immunity.
      Using qRT-PCR, we analyzed the immune gene expression patterns in mucus of Labeo
      rohita experimentally infected with an ectoparasite Argulus siamensis. Mucus
      samples were collected at 0 h, 12 h, 24 h, 3 d, 7 d, 15 d, and 30 d post
      challenge of L. rohita with metanauplii of A. siamensis. All interleukins studied
      herein (IL 6, IL 15, and IL 1beta) showed significant upregulation of expression
      levels in mucus of A. siamensis-infected fish compared to control samples.
      Further, the expression levels of molecules involved in pathogen recognition,
      toll like receptor 22, and pathogen presentation, beta2 microglobulin, were found
      to be significantly upregulated in experimental samples until 7 d post challenge
      compared to control samples. The upregulated expression of lysozyme G at all time
      points post infection indicated the early activation of acute phase responses in
      mucus of infected L. rohita. Moreover, the expression levels of natural killer
      cell enhancing factor B were found to be higher in infected fish than they were
      in the control fish. The early upregulation of the immune genes observed herein
      reinforces the role of mucus as the first line of defense against pathogenic
      assault; furthermore, it expands our understanding of mucosal-immune responses to
      A. siamensis infection, which can aid development of immunological interventions.

PMID- 29351084
TI  - Evaluation of analytical performance of a chemiluminescence enzyme immunoassay
      (CLEIA) for cTnI using the automated AIA-CL2400 platform.

PMID- 29351085
TI  - How to Prepare Interprofessional Teams in Two Weeks: An Innovative Education
      Program Nested in Telehealth.
AB  - PROBLEM: Preparing health professional students for interprofessional
      collaborative practice, especially at a distance where provider shortages prevail
      remains difficult. APPROACH: A two-week interprofessional education (IPE)
      immersion experience preparing students from 11 disciplines and four universities
      was implemented. Week-one, using online technology, students develop/present an
      interprofessional careplan for a complex patient. Students then meet face-to-face
      to conduct group interviews with two standardized patient dyads. Week-two,
      students develop a website for use of the patient dyads. Websites are presented
      to faculty and fellow students via an online virtual meeting space. OUTCOMES: To
      date, 594 students have participated demonstrating capacity to: 1.effectively
      engage in interprofessional care,  2. utilize Telehealth to impact care and break
      down barriers of isolation, and 3. implement skills to advance healthcare.
      CONCLUSION: IPE combined with Telehealth technology provides future providers
      with knowledge and skills for interprofessional care regardless of geographic
      barriers. Next Step: Integrate more technology using mobile devices and enhance
      the evaluation process.

PMID- 29351086
TI  - Active phytoconstituents for diabetes management: A review.

PMID- 29351087
TI  - A depth-encoding PET detector using light sharing and single-ended readout with
      SiPMs.
AB  - Detectors with depth encoding capability and good timing resolution are required
      to develop a high-performance whole-body or total-body PET scanner. In this work,
      depth-encoding PET detectors using light sharing between two discrete crystals
      and single-ended readout with SiPMs were manufactured and evaluated. The
      detectors consisted of two unpolished LYSO crystals of 3*3*20 mm3 with different
      coupling materials between them and were read out by Hamamatsu 3*3 mm2 SiPMs with
      one-to-one coupling. The ratio of the energy of one SiPM to the total energy of
      two SiPMs is used to measure the depth of interaction (DOI). Detector with
      different coupling materials in between the crystals were measured in singles
      mode to find detectors that can provide good DOI resolution. The DOI resolution
      and energy resolution of three types of detectors were measured and the timing
      resolution was measured for the detector with the best DOI and energy resolution.
      The optimum detector with 5 mm optical glue, 9 mm triangle ESR and 6 mm rectangle
      ESR in between the unpolished crystals provides a DOI resolution of 2.65 mm, an
      energy resolution of 10.0% and a timing resolution of 427 ps for events of E>400
      keV. The detectors simultaneously provide good DOI and timing resolution, and
      show great promise to the development of high performance whole body and total
      body PET scanners.

PMID- 29351088
TI  - Fraction-variant beam orientation optimization for non-coplanar IMRT.
AB  - Conventional beam orientation optimization (BOO) algorithms for IMRT assume that
      the same set of beam angles is used for all treatment fractions. In this paper we
      present a BOO formulation based on group sparsity that simultaneously optimizes
      non-coplanar beam angles for all fractions, yielding a fraction-variant (FV)
      treatment plan. Beam angles are selected by solving a multi-fraction fluence map
      optimization problem involving 500-700 candidate beams per fraction, with an
      additional group sparsity term that encourages most candidate beams to be
      inactive. The optimization problem is solved using the fast iterative shrinkage
      thresholding algorithm. Our FV BOO algorithm is used to create five-fraction
      treatment plans for digital phantom, prostate, and lung cases as well as a 30
      fraction plan for a head and neck case. A homogeneous PTV dose coverage is
      maintained in all fractions. The treatment plans are compared with fraction
      invariant plans that use a fixed set of beam angles for all fractions. The FV
      plans reduced OAR mean dose and D 2 values on average by 3.3% and 3.8% of the
      prescription dose, respectively. Notably, mean OAR dose was reduced by 14.3% of
      prescription dose (rectum), 11.6% (penile bulb), 10.7% (seminal vesicle), 5.5%
      (right femur), 3.5% (bladder), 4.0% (normal left lung), 15.5% (cochleas), and
      5.2% (chiasm). D 2 was reduced by 14.9% of prescription dose (right femur), 8.2%
      (penile bulb), 12.7% (proximal bronchus), 4.1% (normal left lung), 15.2%
      (cochleas), 10.1% (orbits), 9.1% (chiasm), 8.7% (brainstem), and 7.1% (parotids).
      Meanwhile, PTV homogeneity defined as D 95/D 5 improved from .92 to .95 (digital
      phantom), from .95 to .98 (prostate case), and from .94 to .97 (lung case), and
      remained constant for the head and neck case. Moreover, the FV plans are
      dosimetrically similar to conventional plans that use twice as many beams per
      fraction. Thus, FV BOO offers the potential to reduce delivery time for non
      coplanar IMRT.

PMID- 29351090
TI  - Parasitic Infections of the Skin and Subcutaneous Tissues.
AB  - A variety of arthropods, protozoa, and helminths infect the skin and subcutaneous
      tissues and may be identified by anatomic pathologists in standard cytology and
      histology preparations. The specific organisms seen vary greatly with the
      patient's exposure history, including travel to or residence in endemic
      countries. Arthropods are the most commonly encountered parasites in the skin and
      subcutaneous tissues and include Sarcoptes scabei, Demodex species, Tunga
      penetrans, and myiasis-causing fly larvae. Protozoal parasites such as Leishmania
      may also be common in some settings. Helminths are less often seen, and include
      round worms (eg, Dirofilaria spp.), tapeworms (eg, Taenia solium, Spirometra
      spp.), and flukes (eg, Schistosoma spp.). This review covers the epidemiologic
      and histopathologic features of common parasitic infections of the skin and
      subcutaneous tissues.

PMID- 29351089
TI  - Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar,
      and Solid.
AB  - Papillary thyroid carcinomas are the most common endocrine cancer and are usually
      associated with good survival. However, some variants of papillary thyroid
      carcinomas may behave more aggressively than classic papillary thyroid
      carcinomas. The tall cell variant of papillary thyroid carcinoma is the most
      common aggressive variant of papillary thyroid carcinoma. The aggressive behavior
      has been ascribed to the histologic subtype and/or to the clinicopathologic
      features, an issue that remains controversial. The columnar variant of papillary
      thyroid carcinoma can be aggressive, particularly in older patients, with larger
      tumors showing a diffusely infiltrative growth pattern and extrathyroidal
      extension. A papillary thyroid carcinoma is designated as solid/trabecular
      variant when all or nearly all of a tumor not belonging to any of the other
      variants has a solid, trabecular, or nested (insular) appearance. This tumor must
      be distinguished from poorly differentiated thyroid carcinoma which has the same
      growth pattern but lacks nuclear features of papillary thyroid carcinoma and may
      show tumor necrosis and high mitotic activity. New to the fourth edition of the
      WHO Classification of Tumours of Endocrine Organs, the hobnail variant of
      papillary thyroid carcinoma is a moderately differentiated papillary thyroid
      carcinoma variant with aggressive clinical behavior and significant mortality.
      All of these variants are histologically unique and important to recognize due to
      their aggressive behavior.

PMID- 29351091
TI  - Circadian Rhythms Disturbances in Alzheimer Disease: Current Concepts, Diagnosis,
      and Management.
AB  - The purpose of this review is to provide an overview of the research regarding
      circadian rhythms in Alzheimer disease (AD). Furthermore, this paper explores the
      role of melatonin in the pathogenesis of AD and the limitation of trials
      addressing circadian rhythms disturbances in the AD population. A literature
      search using Medline with PubMed and Embase was carried out identifying papers
      focusing on circadian rhythms in AD. Sleep disorders and especially circadian
      rhythm disturbances are very common in the elderly population but definitely more
      pronounced in patients with AD. The lack of trials evaluating the management of
      circadian rhythms disorders in the elderly population and especially in AD should
      be considered of the utmost importance. Although there is a better understanding
      about the pathophysiology of AD and its relationship with circadian disorders,
      further studies in human models need to be conducted.

PMID- 29351093
TI  - Coronary intervention for chronic total occlusions: what should the guidelines
      say?

PMID- 29351092
TI  - Political Ideology, Confidence in Science, and Participation in Alzheimer Disease
      Research Studies.
AB  - BACKGROUND: Americans' confidence in science varies based on their political
      ideology. This ideological divide has potentially important effects on citizens'
      engagement with and participation in clinical studies of Alzheimer disease (AD).
      METHODS: A probability sample of 1583 Americans was surveyed about their
      willingness to participate in longitudinal AD research and about their political
      attitudes. These survey results were compared with a survey of 382 participants
      in a longitudinal AD study at the Knight Alzheimer Disease Research Center.
      RESULTS: Among Americans, more conservative ideology decreases willingness to
      participate in a hypothetical longitudinal cohort study of AD both directly and
      through its negative effect on confidence in science. The Knight Alzheimer
      Disease Research Center study participants expressed more liberal ideology and
      greater confidence in science than Americans in general. Of the survey
      respondents opposed to participation, over a quarter changed to neutral or
      positive if the study returned their research results to them. CONCLUSIONS AND
      RELEVANCE: Clinical studies of AD are likely biased toward participants who are
      more liberal and have higher confidence in science than the general population.
      This recruitment bias may be reduced by lowering the trust demanded of
      participants through measures such as returning research results to participants.

PMID- 29351095
TI  - The Effect of Ketorolac on Thoracolumbar Posterolateral Fusion: A Systematic
      Review and Meta-Analysis.
AB  - STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: The purpose of this
      study was to evaluate the effect of postoperative ketorolac administration (ie,
      dosage and duration of use) on pseudarthrosis following thoracolumbar
      posterolateral spinal fusions. SUMMARY OF BACKGROUND DATA: Ketorolac is a
      nonsteroidal anti-inflammatory drug often administered for pain control after
      spine surgery. The main concern with ketorolac is the risk of pseudarthrosis
      following fusion. MATERIALS AND METHODS: A systematic search of multiple medical
      reference databases was conducted for studies detailing postoperative ketorolac
      use in lumbar fusion and scoliosis surgery in adult and pediatric patients,
      respectively. Meta-analysis was performed using the random-effects model for
      heterogeneity as this study analyzes heterogenous patient populations undergoing
      variable approaches to fusion and variable numbers of levels with variable means
      of detection of pseudarthrosis. Outcome measure was pseudarthrosis. RESULTS:
      Overall, 6 studies totaling 1558 patients were reviewed. Pseudarthrosis was
      observed in 119 (7.6%) patients. Pseudarthrosis were observed in adults with
      ketorolac administered for >2 days [odds ratio (OR), 3.44, 95% confidence
      interval (95% CI), 1.87-6.36; P<0.001], adults with doses of >=120 mg/d (OR,
      2.93, 95% CI, 1.06-8.12; P=0.039), and adults with ketorolac administered for >2
      days and at doses >=120 mg/d (OR, 4.75, 95% CI, 2.34-9.62; P<0.001). Ketorolac
      use in smokers was associated with pseudarthrosis (OR, 8.71, 95% CI, 2.23-34.0;
      P=0.002). CONCLUSION: Ketorolac, when administered for >2 days and/or at a dose
      of >=120 mg/d, is associated with pseudarthrosis in adults after posterolateral
      lumbar fusion. Ketorolac use in smokers is also associated with pseudarthrosis.

PMID- 29351094
TI  - Clinical and molecular characterization of nine Chinese patients affected by
      hypofibrinogenemia or dysfibrinogenemia.
AB  - : Congential fibrinogen deficiency is a rare bleeding disorder caused by various
      mutations in three fibrinogen genes. It can be subdivided into four categories:
      afibrinogenemia, hypofibrinogenemia, hypodysfibrinogenemia and dysfbrinogenemia.
      This study was to elucidate the molecular defects in nine unrelated Chinese
      patients with hypofibrinogenemia or dysfibrinogenemia. Three fibrinogen genes
      were amplified by PCR and screened for variants. The identified variants were
      analyzed by bioinformatics prediction and molecular modeling analysis. Genetic
      screening disclosed seven different missense mutations, four of which were novel.
      All of the mutations were expected to impair the protein function/structure as
      assessed by bioinformatics prediction. This study has increased our knowledge of
      the mutational spectrum underlying fibrinogen deficiency.

PMID- 29351096
TI  - Discrepancies in the Definition of "Outpatient" Surgeries and Their Effect on
      Study Outcomes Related to ACDF and Lumbar Discectomy Procedures: A Retrospective
      Analysis of 45,204 Cases.
AB  - STUDY DESIGN: This is a retrospective study. OBJECTIVE: To study the differences
      in definition of "inpatient" and "outpatient" [stated status vs. actual length of
      stay (LOS)], and the effect of defining populations based on the different
      definitions, for anterior cervical discectomy and fusion (ACDF) and lumbar
      discectomy procedures in the American College of Surgeons National Surgical
      Quality Improvement Program (ACS-NSQIP) database. SUMMARY OF BACKGROUND DATA:
      There has been an overall trend toward performing ACDF and lumbar discectomy in
      the outpatient setting. However, with the possibility of patients who underwent
      outpatient surgery staying overnight or longer at the hospital under
      "observation" status, the distinction of "inpatient" and "outpatient" is not
      clear. MATERIALS AND METHODS: Patients who underwent ACDF or lumbar discectomy in
      the 2005-2014 ACS-NSQIP database were identified. Outpatient procedures were
      defined in 1 of 2 ways: either as being termed "outpatient" or hospital LOS=0.
      Differences in definitions were studied. Further, to evaluate the effect of the
      different definitions, 30-day outcomes were compared between "inpatient" and
      "outpatient" and between LOS>0 and LOS=0 for ACDF patients. RESULTS: Of the 4123
      "outpatient" ACDF patients, 919 had LOS=0, whereas 3204 had LOS>0. Of the 13,210
      "inpatient" ACDF patients, 337 had LOS=0, whereas 12,873 had LOS>0. Of the 15,166
      "outpatient" lumbar discectomy patients, 8968 had LOS=0, whereas 6198 had LOS>0.
      Of the 12,705 "inpatient" lumbar discectomy patients, 814 had LOS=0, whereas
      11,891 had LOS>0. On multivariate analysis of ACDF patients, when comparing
      "inpatient" with "outpatient" and "LOS>0" with "LOS=0" there were differences in
      risks for adverse outcomes based on the definition of outpatient status.
      CONCLUSIONS: When evaluating the ACS-NSQIP population, ACDF and lumbar discectomy
      procedures recorded as "outpatient" can be misleading and often did not correlate
      with same day discharge. These findings have significant impact on the
      interpretation of existing studies and define an area that needs clarification
      for future studies. LEVEL OF EVIDENCE: Level 3.

PMID- 29351097
TI  - Effect of Epidural Infusion Bolus Delivery Rate on the Duration of Labor
      Analgesia: A Randomized Clinical Trial.
AB  - BACKGROUND: Programmed intermittent boluses of local anesthetic have been shown
      to be superior to continuous infusions for maintenance of labor analgesia. High
      rate epidural boluses increase delivery pressure at the catheter orifice and may
      improve drug distribution in the epidural space. We hypothesized that high-rate
      drug delivery would improve labor analgesia and reduce the requirement for
      provider-administered supplemental boluses for breakthrough pain. METHODS:
      Nulliparous women with a singleton pregnancy at a cervical dilation of less than
      or equal to 5 cm at request for neuraxial analgesia were eligible for this
      superiority-design, double-blind, randomized controlled trial. Neuraxial
      analgesia was initiated with intrathecal fentanyl 25 MUg. The maintenance
      epidural solution was bupivacaine 0.625 mg/ml with fentanyl 1.95 MUg/ml.
      Programmed (every 60 min) intermittent boluses (10 ml) and patient controlled
      bolus (5 ml bolus, lockout interval: 10 min) were administered at a rate of 100
      ml/h (low-rate) or 300 ml/h (high-rate). The primary outcome was percentage of
      patients requiring provider-administered supplemental bolus analgesia. RESULTS:
      One hundred eight women were randomized to the low- and 102 to the high-rate
      group. Provider-administered supplemental bolus doses were requested by 44 of 108
      (40.7%) in the low- and 37 of 102 (36.3%) in the high-rate group (difference 
      4.4%; 95% CI of the difference, -18.5 to 9.1%; P = 0.67). Patient
      requested/delivered epidural bolus ratio and the hourly bupivacaine consumption
      were not different between groups. No subject had an adverse event. CONCLUSIONS:
      Labor analgesia quality, assessed by need for provider- and patient-administered
      supplemental analgesia and hourly bupivacaine consumption was not improved by
      high-rate epidural bolus administration.

PMID- 29351099
TI  - Commentary.

PMID- 29351098
TI  - Prognostic Factors Change Over Time After Hepatectomy for Colorectal Liver
      Metastases: A Multi-institutional, International Analysis of 1099 Patients.
AB  - OBJECTIVE: To evaluate the changing impact of genetic and clinicopathologic
      factors on conditional overall survival (CS) over time in patients with
      resectable colorectal liver metastasis. BACKGROUND: CS estimates account for the
      changing likelihood of survival over time and may reveal the changing impact of
      prognostic factors as time accrues from the date of surgery. METHODS: CS analysis
      was performed in 1099 patients of an international, multi-institutional cohort.
      Three-year CS (CS3) estimates at the "xth" year after surgery were calculated as
      follows: CS3 = CS (x + 3)/CS (x). The standardized difference (d) between CS3
      rates was used to estimate the changing prognostic power of selected variables
      over time. A d < 0.1 indicated very small differences between groups, 0.1 <= d <
      0.3 indicated small differences, 0.3 <= d < 0.5 indicated moderate differences,
      and d >= 0.5 indicated strong differences. RESULTS: According to OS estimates
      calculated at the time of surgery, the presence of BRAF and KRAS mutations, R1
      margin status, resected extrahepatic disease, patient age, primary tumor lymph
      node metastasis, tumor number, and carcinoembryonic antigen levels independently
      predicted worse survival. However, when temporal changes in the prognostic impact
      of these variables were considered using CS3 estimates, BRAF mutation dominated
      prognosis during the first year (d = 0.48), whereas surgeon-related variables
      (ie, surgical margin and resected extrahepatic disease) determined prognosis
      thereafter (d >= 0.5). Traditional clinicopathologic factors affected survival
      constantly, but only to a moderate degree (0.3 <= d < 0.5). CONCLUSIONS: The
      impact of genetic, surgery-related, and clinicopathologic factors on OS and CS3
      changed dramatically over time. Specifically, BRAF mutation status dominated
      prognosis in the first year, whereas positive surgical margins and resected
      extrahepatic disease determined prognosis thereafter.

PMID- 29351100
TI  - Sudden Unexpected Death From Unusually Large Primary Cardiac B-cell Lymphoma.
AB  - Primary cardiac lymphomas represent approximately 1% to 2% of primary cardiac
      neoplasms and 5% of malignant cardiac neoplasms. Here we present a case of sudden
      unexpected death of a middle-aged male resulting from an unusually large cardiac
      B-cell lymphoma. The neoplasm infiltrated the myocardium of the right atrium and
      ventricle and, to a lesser extent, the wall of the left atrium and pulmonary
      trunk. Extensive infiltration of the heart by the primary cardiac lymphoma,
      combined with the complete lack of symptoms, makes this case unusual.

PMID- 29351101
TI  - A Case Report of Sudden Death From Intracardiac Leiomyomatosis.
AB  - Sudden death resulting from intracardiac leiomyomatosis is rare. In this case, a
      50-year-old woman was found to have intracardiac leiomyomatosis, which originated
      in veins in the broad ligament. Tumor filled the entire inferior vena cava and
      extended into the right heart where it had embolized and occluded the right main
      pulmonary artery. The mechanism of death was sudden right heart failure.

PMID- 29351103
TI  - Retraction Re: Expression of Concern. Am J Phys Med Rehabil 2017;96:761.

PMID- 29351102
TI  - Fatal Sickling Triggered by Massive Foreign Particle Embolism: A Case Report of
      Unrecognized Indwelling Venous Catheter Drug Abuse in Sickle Cell Disease.
AB  - Sickle cell disease (SCD) manifests itself with vaso-occlusive episodes leading
      to infarction. Placement of intravascular catheters provides a useful route for
      management of pain crises as well as other complications. However, catheter
      misuse is a commonly unrecognized problem, which can have lethal consequences. We
      present a case of fatal splenic sequestration/hyperhemolysis secondary to foreign
      body pulmonary and systemic embolization due to intravenous administration of
      hydromorphone pills in a young woman with SCD. Morphological identification of
      the embolized particles (crospovidone, microcrystalline cellulose, and
      hydrophilic polymer) was key in understanding the mechanism of death. Foreign
      particle deposition induced a granulomatous inflammatory response that resulted
      in obliteration and distortion of the microvasculature, thus triggering sickling
      with subsequent organ damage. Despite clinical evidence of asplenia and
      microscopic white pulp fibrosis with Gamna-Gandy body formation, unexpectedly for
      the patient's age, the spleen was enlarged by entrapped sickle cells. The
      findings support the possibility that loss of function can coexist with increased
      splenic activity under certain circumstances, an overlooked clinical phenotype of
      SCD. This case illustrates the teaching value of classic autopsy in addition to
      its crucial role in understanding the natural history of complex heterogeneous
      diseases.

PMID- 29351104
TI  - Frequency of blood pressure and estimated glomerular filtration rate monitoring
      in patients affected by hypertension: a retrospective study with 176 565 patients
      in Germany.
AB  - OBJECTIVE: The aim of this study was to analyze the frequency of blood pressure
      (BP) and estimated glomerular filtration rate (eGFR) monitoring in hypertension
      patients followed in primary care practices in Germany. PATIENTS AND METHODS:
      This study included patients who had received at least two hypertension diagnoses
      (ICD-10: I10) in 2016. The primary outcome of this study was the frequency of BP
      and eGFR monitoring in patients with hypertension in the year 2016. The impact of
      the different demographic and clinical variables on the likelihood of receiving
      at least two BP and at least one eGFR tests was analyzed using multivariate
      logistic regression models. These two cutoff values were selected on the basis of
      the recommendations of the European Society of Hypertension and the European
      Society of Cardiology. RESULTS: This study included 176 565 patients, 53.0% of
      whom were women. The mean age was 68.2 years (SD=13.3 years). The mean number of
      BP tests was 1.9 (SD=3.1), whereas the mean number of eGFR tests was 0.2 (SD=0.8)
      in 2016. Only 33.7 and 9.1% of the population received at least two BP tests and
      one eGFR test, respectively. Older age (>60 years), comorbidities (particularly
      diabetes, hyperlipidemia, and renal insufficiency), and the number of
      antihypertensive treatments were associated with higher odds of receiving at
      least two BP and at least one eGFR tests, whereas the duration of hypertension
      was associated negatively with these odds. CONCLUSION: The frequency of BP and
      eGFR monitoring was low in Germany in 2016. Several demographic and clinical
      variables had a significant impact on this frequency.

PMID- 29351105
TI  - Stem cell modeling of lipid genetics.
AB  - PURPOSE OF REVIEW: To summarize recent advances with respect to the use of human
      pluripotent stem cells to study the genetics of blood lipid traits. RECENT
      FINDINGS: Human pluripotent stem cell models have been used to elucidate the
      mechanisms by which genes contribute to dyslipidemia, to discover new lipid
      related DNA variants and genes, and to perform drug screens. SUMMARY: In addition
      to enabling a better understanding of the genetic basis of lipid metabolism,
      human pluripotent stem cells are identifying potential therapeutic targets as
      well as potential therapies.

PMID- 29351106
TI  - The role of patient registries for rare genetic lipid disorders.
AB  - PURPOSE OF REVIEW: We review the role, utility and current status of patient
      registries for rare genetic lipid disorders. RECENT FINDINGS: The creation and
      maintenance of rare genetic lipid disorder patient registries is critical for
      disease monitoring, improving clinical best practice, facilitating research and
      enabling the development of novel therapeutics. An open-source disease registry
      platform, termed the Rare Disease Registry Framework, has been developed,
      optimized and deployed for homozygous familial hypercholesterolemia. A global
      disease-specific registry for lipoprotein lipase deficiency (LPLD), GENetherapy
      In the mAnagement of Lipoprotein Lipase deficiency, has been established with the
      aim of enrolling 20-40% of LPLD patients worldwide and will study the natural
      history of LPLD as well as therapeutic response to the gene therapy alipogene
      tiparvovec. Similarly, a registry for lysosomal acid lipase deficiency patients
      in Europe and the United States is studying the clinical outcomes of the enzyme
      replacement therapy sebelipase alfa. SUMMARY: There are currently few disease
      specific rare lipid disorder patient registries. The very nature of rare genetic
      lipid disorders would suggest that larger national or international registries
      are necessary to capture clinical data on a sufficient number of patients to
      provide insight into the prevalence and natural history of these conditions.
      Furthermore, these registries can help to identify and address deficiencies in
      current diagnostic and management practices, and facilitate clinical trials of
      new therapies.

PMID- 29351107
TI  - Update on skin and soft tissue infections.

PMID- 29351108
TI  - Neuroimaging in neurodevelopmental disorders: focus on resting-state fMRI
      analysis of intrinsic functional brain connectivity.
AB  - PURPOSE OF REVIEW: Resting-state fMRI assessment of instrinsic functional brain
      connectivity (rs-fcMRI) in autism spectrum disorders (ASD) allows assessment of
      participants with a wide range of functioning levels, and collection of multisite
      databases that facilitate large-scale analysis. These heterogeneous multisite
      data present both promise and methodological challenge. Herein, we provide an
      overview of recent (1 October 2016-1 November 2017) empirical research on ASD rs
      fcMRI, focusing on work that helps clarify how best to leverage the power of
      these data. RECENT FINDINGS: Recent research indicates that larger samples,
      careful atlas selection, and attention to eye status of participants will improve
      the sensitivity and power of resting-state fMRI analyses conducted using
      multisite data. Use of bandpass filters that extend into a slightly higher
      frequency range than typical defaults may prevent loss of disease-relevant
      information. Connectivity-based parcellation as an approach to region of interest
      analyses may allow for improved understanding of functional connectivity
      disruptions in ASD. Treatment approaches using rs-fcMRI to determine target
      engagement, predict treatment, or facilitate neurofeedback demonstrate promise.
      SUMMARY: Rs-fcMRI data have great promise for biomarker identification and
      treatment development in ASD; however, ongoing methodological development and
      evaluation is crucial for progress.

PMID- 29351109
TI  - Coordination of the Environmental influences on Child Health Outcomes program: so
      the whole is greater than the sum of its parts.
AB  - PURPOSE OF REVIEW: The Environmental influences on Child Health Outcomes (ECHO)
      program's mission is to enhance the health of children for generations to come.
      In this manuscript, we describe the structure of the ECHO Coordinating Center
      (ECHO-CC) and its role in developing the infrastructure for the ECHO program.
      RECENT FINDINGS: The ECHO-CC supports ECHO's mission by developing the framework
      of the ECHO program, coordinating multiple levels of membership in the ECHO
      community, developing ECHO policies and procedures, and fostering communication
      and engagement inside and outside of ECHO. SUMMARY: The ECHO-CC has used a number
      of innovative methods for organization, communication, and engagement to enable
      the ECHO program to become greater than the sum of its parts.

PMID- 29351110
TI  - Low cholesterol, impulsivity and violence revisited.
AB  - PURPOSE OF REVIEW: To summarize the recent findings on the association of
      cholesterol levels with impulsivity and violence. RECENT FINDINGS: Several
      authors have recently highlighted the importance of confounding factors that mask
      the association between cholesterol and impulsivity or violent behaviour. In
      particular, demographic factors and presence of psychiatric disorders can play a
      role in the discrepancies present in literature. Men seem to be more sensitive to
      low cholesterol levels as the association between low cholesterol levels and
      aggression is found mostly in men. Cholesterol may play a role as a moderator of
      the serotonergic function and interact with associations between relevant gene
      variants and impulsivity. Lowering cholesterol levels with statins brings about
      several changes in the serotonergic system, nerve cell membrane microviscosity
      and behaviour, and needs to be done with precaution in susceptible individuals.
      Cholesterol levels could serve as a biological risk marker for violence and
      suicidal tendencies in psychiatric patients with depression and schizophrenia.
      SUMMARY: Future studies should consider the potential nonlinearity in the
      association of cholesterol levels with impulsivity, and dependence of the
      association on gender, psychiatric condition, and environmental factors.

PMID- 29351112
TI  - Dimensional Variations in the Soft Tissue Profile After Removal of Implant
      Supported Fixed Interim Restorations: A Pilot Clinical Study.
AB  - PURPOSE: To measure dimensional changes of the periimplant soft tissue profile
      after removal of a single implant fixed interim restorations using digital
      impression procedures. MATERIALS AND METHODS: Ten participants presenting with
      single implant-supported fixed interim restorations (ISFIRs) on the maxillary
      esthetic zone. A 2-step silicone impression was made of the maxillary arch with
      the ISFIRs. The experimental procedure was obtained by making digital impressions
      of the gingival contours immediately after ISFIR removal. The control procedure
      was formed by fabricating definitive casts from the conventional impression using
      the ISFIRs as a customized impression transfer and making digital impressions of
      these definitive casts. Both images of paired groups were digitally overlapped on
      the computer, and their profiles were measured at the coronal, midlevel gingiva
      in the buccolingual and mesiodistal width. RESULTS: Statistically significant
      differences between the ISFIR emergence profile width and the unsupported soft
      tissue profile width were observed at the midlevel gingiva in the buccolingual
      dimension (1.35 mm) and at the coronal (0.51 mm) and midlevel gingiva (1.29 mm)
      in the mesiodistal dimension. CONCLUSIONS: A digital impression, as used in this
      pilot study, does not capture accurately the desired soft tissue dimensions
      immediately after removal of the ISFIR.

PMID- 29351111
TI  - Novel Bronchoscopic Management of Airway Bleeding With Absorbable Gelatin and
      Thrombin Slurry.
AB  - BACKGROUND: Airway bleeding, either spontaneous or as a result of bronchoscopy,
      is associated with significant morbidity and mortality. Multiple bronchoscopic
      techniques are available to achieve complete hemostasis or as a bridge to
      definitive therapies. METHODS: We report our experience on the feasibility of
      endobronchial instillation of an absorbable gelatin and thrombin slurry (GTS) for
      the treatment of spontaneous hemoptysis and procedure-related bleeding. RESULTS:
      We identified 13 cases in which GTS was used for endobronchial hemostasis when
      standard bronchoscopic measures like cold saline, epinephrine, and in some cases
      balloon occlusion were not successful. GTS was delivered through the working
      channel of the bronchoscope in 10 cases and through the distal port of a
      bronchial blocker in the remaining 3 cases. Median age was 69 years (range, 52 to
      79 y). Eight cases corresponded to spontaneous hemoptysis and 5 cases to
      diagnostic or therapeutic procedures. Bleeding was considered severe in 9 (70%)
      cases. All but 1 case were associated with malignancy. Hemostasis was achieved in
      10 (77%) cases by using standard measures in addition to GTS. No patient adverse
      events at 30 days or damage to the equipment were identified. CONCLUSIONS:
      Bronchoscopic instillation of an absorbable GTS is feasible and may be used in
      cases of spontaneous or procedure-related bleeding in addition to conventional
      measures. It can be delivered through the working channel of the bronchoscope or
      through the distal port available in some bronchial blockers. Controlled studies
      are necessary to determine the safety and efficacy of this novel technique.

PMID- 29351113
TI  - Fatigue Failure of External Hexagon Connections on Cemented Implant-Supported
      Crowns.
AB  - PURPOSE: To evaluate the probability of survival and failure modes of different
      external hexagon connection systems restored with anterior cement-retained single
      unit crowns. The postulated null hypothesis was that there would be no
      differences under accelerated life testing. MATERIALS AND METHODS: Fifty-four
      external hexagon dental implants (~4 mm diameter) were used for single cement
      retained crown replacement and divided into 3 groups: (3i) Full OSSEOTITE, Biomet
      3i (n = 18); (OL) OEX P4, Osseolife Implants (n = 18); and (IL) Unihex, Intra
      Lock International (n = 18). Abutments were torqued to the implants, and
      maxillary central incisor crowns were cemented and subjected to step-stress
      accelerated life testing in water. Use-level probability Weibull curves and
      probability of survival for a mission of 100,000 cycles at 200 N (95% 2-sided
      confidence intervals) were calculated. Stereo and scanning electron microscopes
      were used for failure inspection. RESULTS: The beta values for 3i, OL, and IL
      (1.60, 1.69, and 1.23, respectively) indicated that fatigue accelerated the
      failure of the 3 groups. Reliability for the 3i and OL (41% and 68%,
      respectively) was not different between each other, but both were significantly
      lower than IL group (98%). Abutment screw fracture was the failure mode
      consistently observed in all groups. CONCLUSION: Because the reliability was
      significantly different between the 3 groups, our postulated null hypothesis was
      rejected.

PMID- 29351114
TI  - Sexual and reproductive issues and inflammatory bowel disease: a neglected topic
      in men.
AB  - There has been considerable literature on sexual issues in women with
      inflammatory bowel disease (IBD), but relatively little attention has been paid
      to these aspects in men. To review the available literature and to provide the
      best management of sexual and reproductive issues in male patients with IBD. The
      scientific literature on sexual and reproductive issues in men with IBD was
      reviewed. Several factors, including surgical and medication treatments, disease
      activity, lifestyle, and psychological factors, may play a role in the
      development of infertility and sexual dysfunction and may negatively impact
      pregnancy outcomes. Proctocolectomy with ileal pouch-anal anastomosis increases
      the risk of erectile and ejaculatory dysfunction by up to 26%. A treatment with
      sildenafil can be effective. Sperm banking should be advised to young men with
      IBD before surgery. Both sulfasalazine and methotrexate may be responsible for
      reversible sexual dysfunction and infertility. Furthermore, sulfasalazine should
      be switched to mesalazine at least 4 months before conception because of a higher
      risk of congenital malformations in pregnancies fathered by men treated with this
      drug. Psychotropic drugs, frequently used in IBD, may cause sexual dysfunction up
      to 80%. Last but not the least, voluntary childlessness occurs frequently, mainly
      because of concerns about medication safety in pregnancy and fear of transmitting
      disease. Accurate counseling, and where necessary, psychological support can
      decrease any misperceptions and fears. Close collaboration between the
      gastroenterologist and the patient is recommended for the best management of
      these relevant, neglected aspects in men with IBD.

PMID- 29351116
TI  - Treatment of Postpartum Depression: Recommendations for the Clinician.
AB  - Postpartum depression is a significant public health problem affecting almost
      600,000 US women every year. It may arise de novo in the postpartum period or
      continue from pregnancy. A number of evidence-based psychotherapies and medical
      treatments exist for major depression and postpartum depression. The obstetrical
      team has many opportunities to identify high risk and depressed women and refer
      them to mental health professionals or begin treatment with antidepressant
      medication. Careful assessment of risk factors for postpartum depression during
      pregnancy and monitoring depressive symptoms during pregnancy and the postpartum
      period will lead to better outcomes for women and their families.

PMID- 29351115
TI  - Synergistic increase in cardiovascular risk in diabetes mellitus with
      nonalcoholic fatty liver disease: a meta-analysis.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been linked to an
      increased risk of cardiovascular disease (CVD). To explore the impact of diabetes
      mellitus (DM) as a cardiovascular risk factor, this meta-analysis quantitatively
      assessed the association of NAFLD and CVD in diabetic patients. METHODS: PubMed,
      EMBASE, and the Cochrane Library database were analyzed until the end of March
      2017. Original studies analyzing the association between NAFLD and cardiovascular
      risk factors in the diabetic population were included. The available data related
      to outcome were extracted for the effect estimate using a random-effects model.
      The quality of the included studies was assessed using the Newcastle-Ottawa
      Quality Assessment Scale. RESULTS: Of the 770 initially identified studies, 11
      studies involving 8346 patients were finally included. The Newcastle-Ottawa
      Quality Assessment Scale scores suggested that the studies included were of high
      quality. The pooled effects estimate showed that diabetic patients with NAFLD
      showed a two times increased risk for CVD compared with patients without NAFLD
      (odds ratio=2.20, 95% confidence interval: 1.67-2.90). Subgroup analysis also
      yielded a markedly increased risk, with odds ratio (95% confidence interval)
      values of 2.28 (1.61-3.23) and 1.90 (1.48-2.45) in cross-sectional and cohort
      studies, respectively. CONCLUSION: This is the first meta-analysis investigating
      the relationship between NAFLD and CVD independent of the impact of DM. Our
      findings suggested that NAFLD increases the risk of CVD in populations with
      comparable DM profiles. Diabetic patients diagnosed with NAFLD might benefit from
      a more early cardiovascular risk assessment, thereby reducing CVD morbidity and
      mortality.

PMID- 29351117
TI  - Associations of Comorbid Anxiety With Medication Adherence and Psychiatric
      Symptomatology in a Population of Nonadherent Bipolar Disorder Subjects.
AB  - This analysis was conducted on baseline data from 178 nonadherent bipolar
      disorder subjects in a randomized controlled trial. Medication adherence was
      measured with Tablets Routine Questionnaire as percentage of days with missed
      doses. Inclusion criteria required at least 20% nonadherence. Medication
      adherence, symptomatology, and functioning in individuals with and without a
      comorbid anxiety disorder were compared. There were 78.9% of subjects who had at
      least one or more current anxiety disorder, with the most common being
      posttraumatic stress disorder, panic disorder, and generalized anxiety disorder.
      The percentage of days with missed doses over the past month was significantly
      lower in those with anxiety disorders compared with those without (40.1% vs
      50.5%, p = 0.03). Those with comorbid anxiety disorders and those with greater
      number of anxiety disorder diagnoses had significantly worse mean scores on the
      Montgomery-Asberg Depression Rating Scale, Brief Psychiatric Rating Scale,
      Clinical Global Impression-Bipolar Version, and Global Assessment of Functioning.

PMID- 29351118
TI  - Multiple Eyelid Cysts (Apocrine and Eccrine Hidrocystomas, Trichilemmal Cyst, and
      Hybrid Cyst) in a Patient With a Prolactinoma.
AB  - A 53-year-old man presented with smooth-domed, variegated cysts (polycystic
      disease) of all 4 eyelids, worse on the left side. Some of the cysts were clear,
      while others were creamy-white colored. In addition, multiple, very fine
      vesicopapules were noted along the eyelid margins. Histopathologic examination
      revealed a trichilemmal cyst, several pure apocrine hidrocystomas displaying
      multiple chambers, a hybrid cyst, and many small eccrine cysts of the deep
      dermis. The apocrine lesions, including the small ones at the eyelid margins,
      predominated. Smooth muscle actin sometimes positively stained outer
      myoepithelial cells in some of the apocrine cysts, which helped to distinguish
      them from eccrine cysts. Most noteworthy was the fact that the patient had been
      diagnosed with a prolactinoma 20 years earlier. There is only 1 previous report
      of multiple apocrine cysts and an antecedent prolactinoma in the dermatologic
      literature. This syndrome should be separated from that of Schopf-Schulz
      Passarge, which manifests multiple small eyelid apocrine cysts and other
      ectodermal dysplasias without any association with neoplasia, and from that of
      focal dermal hypoplasia (Goltz-Gorlin) syndrome with apocrine cysts but again
      without neoplasia.

PMID- 29351119
TI  - Conjunctival Dirofilariasis Causing Symptoms for 1 Day.

PMID- 29351120
TI  - Grading Using Ki-67 Index and Mitotic Rate Increases the Prognostic Accuracy of
      Pancreatic Neuroendocrine Tumors.
AB  - OBJECTIVES: To measure the usefulness of Ki-67 proliferative index (Ki-67 index)
      as a prognostic variable for grading pancreatic neuroendocrine tumors. METHODS: A
      multi-institutional prospective database comprising 350 patients. Grading based
      on mitotic activity (<2 mitoses/10 high-power fields, 2-20 and >20) and Ki-67
      index (<3% per 10 high-power fields, 3%-20% and >20%). Final grade selected based
      on higher grade of either variable. RESULTS: Most patients were in the less than
      3% (n = 158) and 3% to 20% Ki-67 category (n = 107), with a minority being high
      grade (Ki-67 > 20%, n = 27). Discordance between Ki-67 and mitotic rate was noted
      in 58 patients. On multivariate analysis, final-grade (grade 2: P = 0.010, hazard
      ratio [HR], 1.2; grade 3: P = 0.002; HR, 2.8), Ki-67, mitotic rate, and lymph
      node status were significant prognostic markers for overall survival (OS). For
      disease-free survival (DFS), only final-grade (grade 2: P = 0.05; HR, 1.4; grade
      3: P = 0.009; HR, 2.3), Ki-67, mitotic rate, and margin status significantly
      predicted DFS. Ki-67 was a better model for OS and mitotic rate for DFS. Overall
      combined final grade was the best model based on HR. CONCLUSION: Ki-67 is a
      strong prognostic factor for OS and DFS and should be included in all pancreatic
      neuroendocrine tumor pathology.

PMID- 29351121
TI  - Serum Immunoglobulin G4 in Discriminating Autoimmune Pancreatitis From Pancreatic
      Cancer: A Diagnostic Meta-analysis.
AB  - OBJECTIVE: Differentiation between autoimmune pancreatitis (AIP) and pancreatic
      cancer (PC) is a clinical challenge. Emerging published data on the accuracy of
      serum immunoglobulin G4 (IgG4) for the differential diagnosis between AIP and PC
      are inconsistent. The objective of our study was to perform a meta-analysis
      evaluating the clinical utility of serum IgG4 in the differential diagnosis
      between AIP and PC. METHODS: We performed a systematic literature search of
      multiple electronic databases. The methodological quality of each study was
      assessed according to the Quality Assessment of Diagnostic Accuracy Studies
      checklist. Random-effects model was used to summarize the diagnostic odds ratio
      and other measures of accuracy. RESULTS: Eleven studies comprising 523 AIP
      patients and 771 PC patients were included in the meta-analysis. The summary
      estimates for serum IgG4 in distinguishing AIP from PC were as follows:
      diagnostic odds ratio, 57.30 (95% confidence interval [CI], 23.17-141.67);
      sensitivity, 0.72 (95% CI, 0.68-0.76); specificity, 0.93 (95% CI, 0.91-0.94). The
      area under the curve of serum IgG4 in distinguishing AIP from PC was 0.9200.
      CONCLUSIONS: Our meta-analysis found that serum IgG4 has high specificity and
      relatively low sensitivity in the differential diagnosis between AIP and PC.
      Therefore, serum IgG4 is useful in distinguishing AIP from PC.

PMID- 29351122
TI  - How to Reliably Assess Nodal Status in Distal Pancreatectomy for Adenocarcinoma.
AB  - OBJECTIVES: The optimal number of lymph nodes that need to be analyzed to
      reliably assess nodal status in distal pancreatectomy for adenocarcinoma is still
      unknown. METHODS: Two hundred seventy-eight patients who underwent distal
      pancreatectomy for adenocarcinoma were retrieved from a retrospective French
      nationwide database. The relations between the number of analyzed lymph nodes and
      the nodal status of the tumor were studied. The beta-binomial law was used to
      estimate the probability of being truly node negative depending on the number of
      analyzed lymph nodes. Cox proportional hazard model was used for the survival
      analysis. RESULTS: The median number of analyzed lymph nodes was 15. There was a
      positive correlation between the number of positive lymph nodes and the number of
      lymph nodes analyzed. The curve reached a plateau at approximately 25 lymph
      nodes. The beta binomial model demonstrated that an analysis of 21 negative lymph
      nodes shows a probability to be truly N0 at 95%. N+ status was associated with
      survival, but the number of lymph node analyzed was not. CONCLUSION: At least 21
      lymph nodes should be analyzed to ensure a reliable assessment of the nodal
      status, but this number may be hard to reach in distal pancreatectomy.

PMID- 29351123
TI  - Accuracy of 18F-NaF PET/CT in bone metastasis detection and its effect on patient
      management in patients with breast carcinoma.
AB  - OBJECTIVE: Determination of the accuracy of sodium fluorine-18-fluoride (F-NaF)
      PET/computed tomography (CT) for the evaluation of bone metastases, and the
      impact on patient management in breast cancer patients. PATIENTS AND METHODS:
      Patients with breast cancer, referred for F-NaF PET/CT between February 2014 and
      June 2016, were included in a database. Baseline characteristics, clinical
      indication, definitive diagnosis according to follow-up data, as well as changes
      in patient management were recorded. Follow-up was performed during a period of
      at least 6 months using histopathologic, medical imaging, biochemical, and
      clinical data. RESULTS: A total of 118 patients were included in the study.
      Indications for F-NaF PET/CT included primary staging (12%), follow-up (31%),
      bone pain (52%), abnormal laboratory findings (5%), and evaluation of equivocal
      osseous lesions on other imaging modalities (3%). Bone metastases were found in
      42%, whereas 53% of the scans were negative and 5% yielded equivocal results.
      Correlation with the reference standard yielded a sensitivity of 0.96, a
      specificity of 0.91, a positive predictive value of 0.89, a negative predictive
      value of 0.97, and an accuracy of 0.93. In 25% of the patients, the scan results
      led to alterations in patient management. F-NaF PET/CT for the evaluation of bone
      pain showed no explanation in 29%, benign pathology in 66%, and bone metastases
      in 5%. CONCLUSION: In the present cohort of patients with breast cancer, F-NaF
      PET/CT detected bone metastases in 42% with an accuracy of 0.93. The scan results
      led to a change in patient management in 25%. In the evaluation of bone pain, an
      explanation for pain was found in 71% of the scans.

PMID- 29351124
TI  - Feasibility assessment of yttrium-90 liver radioembolization imaging using
      amplitude-based gated PET/CT.
AB  - PURPOSE: The usage of PET/computed tomography (CT) to monitor hepatocellular
      carcinoma patients following yttrium-90 (Y) radioembolization has increased.
      Respiratory motion causes liver movement, which can be corrected using gating
      techniques at the expense of added noise. This work examines the use of amplitude
      based gating on Y-PET/CT and its potential impact on diagnostic integrity.
      PATIENTS AND METHODS: Patients were imaged using PET/CT following Y
      radioembolization. A respiratory band was used to collect respiratory cycle data.
      Patient data were processed as both standard and motion-corrected images. Regions
      of interest were drawn and compared using three methods. Activity concentrations
      were calculated and converted into dose estimates using previously determined and
      published scaling factors. Diagnostic assessments were performed using a binary
      scale created from published Y-PET/CT image interpretation guidelines. RESULTS:
      Estimates of radiation dose were increased (P<0.05) when using amplitude-gating
      methods with Y PET/CT imaging. Motion-corrected images show increased noise, but
      the diagnostic determination of success, using the Kao criteria, did not change
      between static and motion-corrected data. CONCLUSION: Amplitude-gated PET/CT
      following Y radioembolization is feasible and may improve Y dose estimates while
      maintaining diagnostic assessment integrity.

PMID- 29351125
TI  - Central inhibition of granulocyte-macrophage colony-stimulating factor is
      analgesic in experimental neuropathic pain.
AB  - With less than 50% of patients responding to the current standard of care and
      poor efficacy and selectivity of current treatments, neuropathic pain continues
      to be an area of considerable unmet medical need. Biological therapeutics such as
      monoclonal antibodies (mAbs) provide better intrinsic selectivity; however,
      delivery to the central nervous system (CNS) remains a challenge. Granulocyte
      macrophage colony-stimulating factor (GM-CSF) is well described in inflammation
      induced pain, and early-phase clinical trials evaluating its antagonism have
      exemplified its importance as a peripheral pain target. Here, we investigate the
      role of this cytokine in a murine model of traumatic nerve injury and show that
      deletion of the GM-CSF receptor or treatment with an antagonizing mAb alleviates
      pain. We also demonstrate enhanced analgesic efficacy using an engineered
      construct that has greater capacity to penetrate the CNS. Despite observing GM
      CSF receptor expression in microglia and astrocytes, the gliosis response in the
      dorsal horn was not altered in nerve injured knockout mice compared with wild
      type littermate controls as evaluated by ionized calcium binding adapter molecule
      1 (Iba1) and glial fibrillary acidic protein, respectively. Functional analysis
      of glial cells revealed that pretreatment with GM-CSF potentiated
      lipopolysaccharide-induced release of proinflammatory cytokines. In summary, our
      data indicate that GM-CSF is a proinflammatory cytokine that contributes to
      nociceptive signalling through driving spinal glial cell secretion of
      proinflammatory mediators. In addition, we report a successful approach to
      accessing CNS pain targets, providing promise for central compartment delivery of
      analgesics.

PMID- 29351126
TI  - Incidence and Risk Factors for Falls in Women With End-Stage Hip Osteoarthritis.
AB  - BACKGROUND AND PURPOSE: Fall-induced injuries and resulting deaths are a serious
      health problem among older adults. The most common risk factors for falls in
      older adults are muscle weakness, gait deficiencies, and balance deficits.
      Patients with end-stage hip osteoarthritis (OA) also have many hip dysfunctions,
      and these all have the potential to increase the risk of falls. However, the
      incidence and risk factors for falls in patients with end-stage hip OA remain
      unclear. The aim of this study was to determine the incidence of falls in women
      with end-stage hip OA and to identify risk factors for falls in this patient
      population. METHODS: This study was a cross-sectional analysis. One hundred fifty
      three women with end-stage hip OA (mean age = 64.0 years) and 112 age-matched
      healthy women (mean age = 64.1 years) were analyzed using available data. All
      participants were examined for the number and circumstances of falls in the past
      year. The circumstances of falls included the location, time, direction, cause,
      and injury. We examined the outcome of hip function, ambulatory ability, physical
      activity, and limping severity in women with end-stage hip OA. Multivariate
      logistic regression analysis was used to identify factors influencing falls in
      women with hip OA. RESULTS: The incidence of at least 1 fall in the past year was
      significantly higher in women with end-stage hip OA (30.1%) than in healthy women
      (12.5%) (P < .001). Falls in women with end-stage hip OA were most often caused
      by tripping and falling forward during the daytime. The majority of falls (65.2%)
      resulted in injuries and 13.0% resulted in fractures. The occurrence of a fall
      significantly correlated with limping (odds ratio = 3.26, 95% confidence interval
      = 1.49-7.14, P = .003) and knee extensor muscle strength (odds ratio = 0.22, 95%
      confidence interval = 0.05-0.85, P = .029). CONCLUSIONS: Women with end-stage hip
      OA have an increased risk of falls and fall-induced injuries. The prevention of
      falls in this vulnerable population should be a priority among health care
      practitioners. In particular, women who are limping and have reduced lower knee
      extensor strength should take care to avoid falls.

PMID- 29351127
TI  - Four Months of Wearing a Balance Orthotic Improves Measures of Balance and
      Mobility Among a Cohort of Community-Living Older Adults.
AB  - BACKGROUND AND PURPOSE: The Centers for Disease Control and Prevention estimated
      that there were 29 million falls and 7 million injuries in 2014 in the United
      States. Falls, decreased balance, and mobility disability are common in older
      adults and often result in loss of independence. Finding interventions to address
      these issues is important, as this age group is growing exponentially. Prior
      studies indicate balance and mobility can be improved by the balance-based torso
      weighting (BBTW) assessment implemented through wear of a balance orthotic (BO).
      This study sought to determine the impact of wearing a BO on balance, mobility,
      and fall risk over time. METHODS: This quasiexperimental, 1-group pre-/posttest
      study investigated the effect of 4 months of daily wear (4 hours per day) of a BO
      on mobility, balance, and falls efficacy in 30 older adults living in a
      retirement community with limited mobility defined by a Short Physical
      Performance Battery (SPPB) score range between 4 and 9 out of a maximum of 12
      points. Pre- and posttreatment tests included the Timed Up and Go (TUG),
      Functional Gait Assessment (FGA), Falls Efficacy Scale (FES), and SPPB.
      Participants received the BBTW assessment, consisting of individualized
      assessment of 3-dimensional balance loss, and treatment with a strategically
      weighted and fitted BO to control balance loss. The BO was worn twice a day for 2
      hours (4 hours per day) for 4 months. Participants continued regular activity and
      no other interventions were provided. All posttests were conducted after 4 months
      and at least 8 hours after removal of the BO. Subitems from the SPPB (gait speed
      [GS], 5-time sit-to-stand [FTSST], and tandem stance time [TST]) were analyzed as
      separate outcome measures. Data were analyzed with paired t tests with a
      Bonferroni correction (SPPB, GS, FGA, and FES) when statistical assumptions were
      met. Data that did not meet the statistical assumptions of the paired t test
      (FTSST, TST, and TUG) were analyzed with Wilcoxon signed rank tests with a
      Bonferroni correction. RESULTS AND DISCUSSION: Twenty-four subjects, average age
      87 (5.7) years, completed the study. Paired t tests indicated that mean group
      scores on the SPPB, GS, and FGA significantly improved from pre- to posttests.
      The SPPB improved by 1.3 points (P = .001). GS improved by 0.09 m/s (P = .004)
      and both mean values improved beyond fall risk cutoffs. The FGA also improved by
      2.6 points (P = .001). There were no significant changes in FES scores (P =
      .110). Wilcoxon signed rank tests indicated median group scores of the FTSST
      significantly improved from pre- to posttests by 7.4 seconds (P = .002) and
      median TUG times improved by 3.5 seconds (P = .004). There were no changes in TST
      (P = .117). CONCLUSIONS: This study suggests that wearing a BO for 4 hours per
      day for 4 months results in improvements in functional assessments related to
      fall risk (SPPB, GS, FGA, TUG, and FTSST) in a group of older adult participants
      with limited mobility.

PMID- 29351128
TI  - Fluid Removal With Ultrasound Guided Protocol Improves the Efficacy and Safety of
      Dehydration in Post-Resuscitated Critically Ill Patients: A Quasi-Experimental,
      Before and After Study.
AB  - Fluid overload is associated with increased morbidity and mortality in critically
      ill patients. However, researches rarely study the precise start or end point of
      fluid removal and no protocol was developed to control the fluid removal process.
      We hypothesized that individualized fluid removal with ultrasound-guided protocol
      could improve the efficacy and safety of fluid removal in post-resuscitated
      critically ill patients. A quasi-experimental, before and after trial was
      conducted to identify the benefits of ultrasound-guided fluid removal. Fluid
      removal was performed either following the doctor's experience in Control group,
      or abiding the ultrasound guided protocol in Ultrasound group. The study end
      points were the start time, end time, length of fluid removal, and the
      complications related to fluid removal. A total of 85 subjects were finally
      analyzed in this study. The fluid removal was started earlier, completed quicker
      and ended earlier (21.0 +/- 14.6 h vs. 35.1 +/- 26.5 h, 49.8 +/- 32.6 vs. 93.0 +/
      42.8 h, 69.0 +/- 32.2 h vs. 126.4 +/- 52.5 h, P < 0.05) in Ultrasound group than
      in Control. The subjects had more daily negative fluid balance and urine output (
      990.4 +/- 636.1 mL vs. -723.6 +/- 549.5 mL, 2425.8 +/- 886.7 mL vs. 1560.7 +/-
      1125.3 mL, P < 0.05) in Ultrasound group. The time of lung B-lines to reduce to
      zero was shorter and B-line at the end point was less (49.5 +/- 36.6 h vs. 75.6
      +/- 58.8 h, 0[1] vs. 0[0], P < 0.05) in Ultrasound group. The length of intensive
      care unit stay in shock subgroup had a tendency to shorten (96.1 +/- 61.5 h vs.
      174.6 +/- 132.0 h, P > 0.05) in Ultrasound group. We concluded that fluid removal
      with individualized ultrasound-guided protocol improves the efficacy and safety
      of dehydration in critically ill patients.

PMID- 29351129
TI  - Impact of Pulmonary Rehabilitation on Exercise Tolerance and Quality of Life in
      Patients With Idiopathic Pulmonary Fibrosis: A SYSTEMATIC REVIEW AND META
      ANALYSIS.
AB  - BACKGROUND: Patients with pulmonary fibrosis are living longer and present with
      an increasing number of comorbidities over time. Pulmonary rehabilitation, as a
      nonpharmacological approach, may be promising in these patients, although there
      is limited information on the impact of pulmonary rehabilitation on exercise
      tolerance and quality of life. Thus, conducting a systematic review and meta
      analysis, the purpose of this study was to determine the effects of pulmonary
      rehabilitation on exercise tolerance and quality of life in patients with
      idiopathic pulmonary fibrosis. METHODS: We searched MEDLINE, Cochrane Library,
      Embase, Scielo, PEDro, and CINAHL (from the earliest date available to June 2016)
      for trials. Study selection included randomized controlled trials (RCTs) that
      examined the effects of pulmonary rehabilitation in patients with idiopathic
      pulmonary fibrosis. Two reviewers selected studies independently. Data were
      extracted from published RCTs. Study quality was evaluated using the PEDro scale.
      Weighted mean differences, standard mean differences, and 95% CIs were
      calculated. RESULTS: We analyzed data from 5 RCTs comparing a pulmonary
      rehabilitation group with a control group. Pulmonary rehabilitation improved
      exercise tolerance weighted mean differences (44 m; 95% CI, 5.3-82.8) compared
      with no exercise. The meta-analyses also showed significant improvement in
      symptoms, impact, and total score from the St George's Respiratory Questionnaire
      for participants in pulmonary rehabilitation compared with control. No serious
      adverse events were reported. CONCLUSION: Pulmonary rehabilitation is effective
      in increasing exercise tolerance and improving quality of life in patients with
      idiopathic pulmonary fibrosis.

PMID- 29351130
TI  - Comparative Effectiveness of Low-Volume Time-Efficient Resistance Training Versus
      Endurance Training in Patients With Heart Failure.
AB  - PURPOSE: Cardiorespiratory fitness is positively related to heart failure (HF)
      prognosis, but lack of time and low energy are barriers for adherence to
      exercise. We, therefore, compared the effect of low-volume time-based resistance
      exercise training (TRE) with aerobic moderate-intensity cycling (AMC) on maximal
      and submaximal exercise capacity, health-related quality of life, and vascular
      function. METHODS: Twenty-eight HF patients (New York Heart Association class I
      II) performed AMC (n = 14) or TRE (n = 14). Maximal and submaximal exercise
      capacity, health-related quality of life, and vascular function were evaluated
      before and after a 6-wk training intervention with 3 training sessions per week.
      The AMC group and the TRE group trained for 45 and 25 min per training session,
      respectively. During the training sessions, the TRE and AMC groups trained at 60
      +/- 4% and 59 +/- 2% (mean +/- standard deviation) of (Equation is included in
      full-text article.)O2peak, respectively. RESULTS: The energy expenditure was
      significantly greater in AMC than in TRE (P < .05). The (Equation is included in
      full-text article.)O2peak and Wattpeak increased in AMC group (P < .001) and TRE
      group (P = .001), with no differences between groups. Six-minute walk distance
      also increased in both groups (AMC, P = .006 and TRE, P = .036), with no
      difference between groups. Health-related quality of life improved equally in the
      2 groups, whereas vascular function did not change in either group. CONCLUSION:
      These results demonstrate that AMC and TRE equally improved exercise capacity and
      health-related quality of life in lower New York Heart Association-stage HF
      patients, despite less time required as well as lower energy expenditure during
      TRE than during AMC. Therefore, TRE might represent a time-efficient exercise
      modality for improving adherence to exercise in patients with class I-II HF.

PMID- 29351131
TI  - Quality of life on long-term parenteral nutrition: can it be an indication for
      intestinal transplantation?
AB  - PURPOSE OF REVIEW: Long-term outcomes in patients with intestinal failure and
      following intestine transplantation have improved significantly over the last
      decade. With these improvements, listing criteria for intestine transplantation
      are reevaluated and the role of quality of life (QoL) in patients' outcome is
      increasingly studied and emphasized. Here, we review the recent literature on QoL
      before and after intestine transplantation and discuss whether QoL should be
      considered as a listing criterion for intestine transplantation. RECENT FINDINGS:
      Patients on home parenteral nutrition, experience lower QoL compared with healthy
      population and equal or lower QoL than patients with other chronic diseases.
      After transplantation, QoL improves and is comparable in some QoL domains to that
      of the general population. These findings are limited by heterogeneous study
      designs and sample size. Although QoL improves after intestine transplantation,
      long-term survival of patients receiving HPN surpass postintestine
      transplantation survival. Poor QoL is not associated with an increased mortality
      in patients receiving HPN. SUMMARY: Current survival outcomes of intestine
      transplantation do not justify poor QoL as a single listing criterion for
      intestine transplantation. However, intestine transplantation should be
      considered in patients with unique circumstances of extremely poor QoL. This
      approach may change once postintestine transplantation patient survival will
      further improve.

PMID- 29351132
TI  - A Mixed-Methods Approach to Humanistic Interprofessional Faculty Development.
AB  - INTRODUCTION: This study evaluated the effectiveness of the Mentoring and
      Professionalism in Training (MAP-IT) program, a longitudinal, interprofessional
      faculty development curriculum designed to enhance clinicians' humanistic
      mentoring skills, specifically nurses and physicians. METHODS: During 2014 to
      2016, two consecutive cohorts of nurses and physicians completed the MAP-IT
      program. Participants included 169 high potential mentors (HPMs) and 61
      facilitator leaders. Each 10-month program consisted of small group work,
      experiential learning, and critical reflection aimed at enhancing humanistic
      mentoring skills. Throughout the program, facilitator leaders served as mentors
      for the HPMs. Both quantitative and qualitative data were collected to measure
      changes in skill levels specific to humanistic teaching practices, as well as
      overall evaluation of the program's curriculum and logistics. Quantitative data
      were analyzed using the Wilcoxon signed-rank test, descriptive statistics, and
      Fisher exact test, as appropriate. Qualitative data assessing the overall impact
      and applicability of the program to the clinical setting were analyzed using
      content analysis methodology. RESULTS: Across cohorts, HPMs demonstrated
      significant increases in perceptions of humanistic teaching skills. During
      objective structured teaching simulations, significant increases were also found
      in HPMs' self-reported mentoring skills and their skills as rated by a
      standardized RN/MD. Qualitative analyses revealed themes of the program to be
      skill development and application, mentorship, humanism, mindfulness, self-care,
      and acknowledgment of overlapping interprofessional roles. DISCUSSION: Utilizing
      an interprofessional education approach, the MAP-IT program was determined to be
      a feasible strategy to positively impact the personal and professional
      development of nurses and physicians.

PMID- 29351133
TI  - Using Clinical Questions Asked by Primary Care Providers Through eConsults to
      Inform Continuing Professional Development.
AB  - INTRODUCTION: Continuing professional development (CPD) offerings should address
      the educational needs of health care providers. Innovative programs, such as
      electronic consultations (eConsults), provide unique educational opportunities
      for practice-based needs assessment. The purpose of this study is to assess
      whether CPD offerings match the needs of physicians by coding and comparing
      session content to clinical questions asked through eConsults. METHODS: This
      study analyzes questions asked by primary care providers between July 2011 and
      January 2015 using a service that allows specialists to provide consultation over
      a secure web-based server. The content of these questions was compared with the
      CPD courses offered in the area in which these primary care providers are
      practicing over a similar period (2012-2014). The clinical questions were
      categorized by the content area. The percentage of questions asked about each
      content area was calculated for each of the 12 specialties consulted. CPD course
      offerings were categorized using the same list of content areas. Percentage of
      minutes dedicated to each content area was calculated for each specialty. The
      percentage of questions asked and the percentage of CPD course minutes for each
      content area were compared. RESULTS: There were numerous congruencies and
      discrepancies between the proportion of questions asked about a given content
      area and the CPD minutes dedicated to it. DISCUSSION: Traditional needs
      assessment may underestimate the need to address topics that are frequently the
      subject of eConsults. Planners should recognize eConsult questions as a valuable
      source of practice-associated challenges that can identify professional
      development needs of physicians.

PMID- 29351134
TI  - Carotid Doppler sonography: additional tool to assess hemodynamic improvement
      after transcatheter aortic valve implantation.
AB  - PURPOSE: The aim of our study was to assess the arterial cerebral blood flow
      variations in patients with aortic valve stenosis, immediately after the
      transcatheter aortic valve implantation (TAVI). METHODS: The study population
      includes 62 consecutive patients who underwent TAVI for aortic valve stenosis
      (95%) and sugical bioprosthesis degeneration (5%). Carotid Doppler examination
      was performed recording blood flow, systolic peak velocity, time average mean
      velocity and mean acceleration time at baseline, after balloon aortic
      valvuloplasty, and within 10 min after the device release. RESULTS: A significant
      improvement of blood flow was recorded at the end of the procedure (from 315.05
      +/- 141.72 to 538.67 +/- 277.46 ml/min; P < 0.00001). The systolic peak velocity
      and the time average mean velocity increased from 52.27 +/- 14.29 to 78.89 +/-
      20.48 cm/s (P < 0.00001) and from 12.24 +/- 4.74 to 21.21 +/- 9 cm/s (P <
      0.00001), respectively. Consensually, the mean acceleration time decreased from
      0.22 +/- 0.02 to 0.03 +/- 0.02 s (P < 0.00001) after the procedure. CONCLUSION:
      Monitoring of Doppler measurements may be a useful and noninvasive method to
      assess acutely the improvement of hemodynamic flow after TAVI, specifically for
      the cerebral district.

PMID- 29351136
TI  - Trends and Variability in the Use of Total Shoulder Arthroplasty for Medicare
      Patients.
AB  - INTRODUCTION: As policies are implemented to encourage high-quality care, it is
      important to identify any persistent limitations to the uniform delivery of
      anatomic and reverse total shoulder arthroplasty (TSA). The study's goal was to
      assess current TSA use and identify predictors of geographic variability.
      METHODS: We used data from 2012 through 2014 that was obtained from public
      Medicare databases to identify the case volume, locations, and names of surgeons
      performing >10 TSAs annually. We also recorded regional characteristics of the
      Medicare population, including demographic characteristics and health factors.
      RESULTS: From 2012 through 2014, the number of surgeons performing >10 TSAs
      annually increased from 824 to 1,060-an increase ranging from 0.75 to 0.95 TSAs
      per 1,000 beneficiaries. In 2012, there were 59 hospital referral regions with no
      TSAs performed; the number of regions decreased to 35 by 2014 (P = 0.009). The
      use of TSA varied widely across regions (range, 0.1 to 6.4 per 1,000
      beneficiaries). A larger proportion of white patients and a smaller proportion of
      patients eligible for Medicaid were independent predictors for increased use of
      TSA. Despite this finding, 74.4% and 96.9% of the US population resided within 50
      km and 200 km, respectively, of a surgeon performing at least 20 TSAs in Medicare
      patients annually. DISCUSSION: TSA utilization in the Medicare population is
      increasing across the country. Although notable geographic disparities in the use
      of TSA persist, increased TSA utilization has provided greater access to surgeons
      with high-volume TSA caseloads. CONCLUSION: Substantial geographic variation in
      TSA use remains, largely due to socioeconomic factors.

PMID- 29351135
TI  - Angiography and Embolization in the Management of Bleeding Pelvic Fractures.
AB  - The use, timing, and priority of angioembolization in the management of bleeding
      pelvic fractures remain ambiguous. The most common vessels for angioembolization
      are, in decreasing order, the internal iliac artery and its branches, the
      superior gluteal artery, the obturator artery, and the internal pudendal artery.
      Technical success rates for this treatment option range from 74% to 100%. The
      fracture patterns most commonly requiring angioembolization are the Young and
      Burgess lateral compression and anterior-posterior compression types and Tile
      type C. Mortality rates after angioembolization of 16% to 50% have been reported,
      but deaths are usually related to concomitant injuries. The sensitivity and
      specificity of contrast-enhanced CT in detecting the need for angioembolization
      range from 60% to 90% and 92% to 100%, respectively. Angioembolization can be
      effective in the management of bleeding pelvic fractures, but as with any
      treatment, the risks of complications must be considered. Availability of
      angioembolization and institutional expertise/preference for the alternative
      strategy of pelvic packing influence its use.

PMID- 29351137
TI  - Early Response to Warfarin Initiation and the Risk of Venous Thromboembolism
      After Total Joint Arthroplasty.
AB  - BACKGROUND: Venous thromboembolism chemoprophylaxis with warfarin is common after
      total joint arthroplasty. Early response to warfarin initiation has been
      theorized to engender a transient increase in the risk of venous thromboembolism.
      We hypothesized that a rapid rise in the international normalized ratio is a risk
      factor for venous thromboembolism after total joint arthroplasty. METHODS: This
      study was a retrospective analysis of Medicare patients undergoing elective total
      joint arthroplasty who were given nomogram-dosed warfarin for venous
      thromboembolism prophylaxis. Logistic regression was used to assess the
      relationship between the postoperative rate of change in the international
      normalized ratio and the occurrence of symptomatic venous thromboembolism within
      30 days postoperatively. RESULTS: The study included 948 patients (715 total knee
      arthroplasty, 233 total hip arthroplasty), of whom 4.4% experienced symptomatic
      venous thromboembolism within 30 days postoperatively. The change in the
      international normalized ratio from postoperative day 1 to postoperative day 2
      was significantly greater in the symptomatic venous thromboembolism group
      compared with the group that did not have venous thromboembolism (increase of
      0.70 versus 0.46; P = 0.008). Regression analysis showed that a higher rate of
      change in the international normalized ratio was associated with increased risk
      of symptomatic venous thromboembolism (odds ratio, 2.59 per unit of change in the
      international normalized ratio; 95% confidence interval, 1.51-4.38; P = 0.001).
      CONCLUSION: A rapid rise in the international normalized ratio after warfarin
      initiation in total joint arthroplasty patients is associated with increased risk
      of symptomatic venous thromboembolism. This novel finding identifies a population
      at risk for this complication. Further study of the early effects of warfarin
      therapy is warranted. LEVEL OF EVIDENCE: Level III.

PMID- 29351138
TI  - The Effect of Melatonin Upon Postacute Withdrawal Among Males in a Residential
      Treatment Program (M-PAWS): A Randomized, Double-blind, Placebo-controlled Trial.
AB  - OBJECTIVE: Assess the effect of melatonin (5 mg) compared with placebo as an
      adjuvant treatment along with current behavioral and pharmacotherapy for 28 days
      on weekly self-reported severity of anxiety, depression, stress, and sleep
      complaints, and also how sleep is affecting daily life in males 18 years of age
      and older in recovery from substance use at a residential program in south
      western Pennsylvania. BACKGROUND: Individuals in recovery experience a variety of
      symptoms including, but are not limited to, anxiety, depression, sleep
      difficulties, and stress. In the U.S., melatonin is a readily available
      nutraceutical that is used to alleviate sleep difficulties. Studies also suggest
      that melatonin may also have anxiolytic and antidepressive actions alone, as well
      as in those with co-morbid insomnia. Observation of clinicians treating
      individuals during and/or post drug cessation indicated that melatonin is
      commonly provided specifically to alleviate sleep difficulties with little
      evidence regarding efficacy in this population. The paucity of evidence as well
      as observation of clinical practices provided the rationale for this randomized
      clinical trial. METHODS: A single-center, randomized, double-blind, placebo
      controlled, parallel-group trial was conducted. Seventy individuals were
      enrolled, block-randomized with an allocation ratio of 1:1. Intention-to-treat
      analysis was performed for all primary outcome measures. Primary outcome measures
      were assessed with the Generalized Anxiety Disorder Scale (GAD-7), Personal
      Health Questionnaire Depression Scale (PHQ-8), Perceived Stress Scale (PSS-14),
      and Pittsburgh Sleep Symptom Questionnaire-Insomnia (PSSQ-1). Secondary outcome
      measures were to acquire participant characteristics, determine adherence, and
      document adverse events. RESULTS: No statistically significant between-group
      differences were detected for baseline characteristics. Even though the
      proportion of individuals reporting an adverse event between groups was not
      significantly different, the frequency of reported adverse events was greater in
      the melatonin group. Intention-to-treat analysis for all the measured outcomes
      revealed no statistically significant between-group differences for same day
      comparisons. CONCLUSIONS: The diversity of medication regimens, and also the
      services provided by the residential treatment site add to the complexity of
      assessing the efficacy of melatonin on the measured outcomes. Given these
      limitations, there exists insufficient evidence to suggest that the effect of
      melatonin and placebo on the outcomes were significantly different.

PMID- 29351140
TI  - Does Performing Preplacement Workplace Hair Drug Testing Influence US Department
      of Transportation Random and Postaccident Urine Drug Test Positivity Rates?
AB  - BACKGROUND: Does performing pre-employment hair drug testing subsequently affect
      the prevalence of positive random and postaccident urine drug tests? METHODS:
      This cross-sectional study was designed to evaluate the prevalence of positive
      postaccident and random workplace urine drug tests for companies that perform pre
      employment hair and urine drug testing to companies that only perform pre
      employment urine drug testing. RESULTS: Fisher exact test of independence
      indicated no significant difference between pre-employment hair drug testing and
      overall US Department of Transportation random and postaccident urine drug test
      positivity rates. CONCLUSIONS: The analysis failed to reject the null hypothesis,
      suggesting that pre-employment hair drug testing had no effect upon random and
      postaccident urine drug test positivity rates.

PMID- 29351139
TI  - A Pilot Randomized Controlled Trial of a Phone-based Intervention for Smoking
      Cessation and Relapse Prevention in the Postpartum Period.
AB  - OBJECTIVES: To pilot-test a Phone-based Postpartum Continuing Care (PPCC)
      protocol developed from existing evidence-based approaches to address both
      postpartum smoking relapse among low-income women who quit smoking during
      pregnancy and postpartum smoking increase among those who had cut down. METHODS:
      One hundred thirty low-income pregnant women who were current or recently quit
      tobacco smokers were recruited at their first prenatal appointment and randomized
      to either a Control (standard care) or Experimental (standard care + PPCC) group.
      An intent-to-treat analysis was conducted on biochemically verified data from 6
      in-person interviews during pregnancy and postpartum. Feasibility with regard to
      recruitment, randomization, assessment, and implementation of PPCC were assessed,
      along with acceptability among the target population. RESULTS: PPCC was found to
      be feasible and acceptable to some participants, but not all. There were no
      significant differences in tobacco products per day at 6 months postpartum
      between groups; however, effect sizes differed at 6 weeks compared with 6 months
      postpartum. Similarly, there were no significant differences between groups in
      cessation rate (24% in each group) and past 90-day tobacco use (59 vs 55 days,
      for Control and Experimental groups, respectively). CONCLUSIONS: The PPCC
      intervention did not differentially reduce tobacco use postpartum compared with a
      controlled comparison group, though it was found to be acceptable among a
      subpopulation of low-income pregnant women and feasible with regard to
      recruitment, randomization, assessment procedures, and implementation. Further
      research is needed to identify an intervention that significantly improves
      smoking relapse rates postpartum.

PMID- 29351141
TI  - An Exploration of Emergency Physicians' Attitudes Toward Patients With Substance
      Use Disorder.
AB  - OBJECTIVES: Much is known about some healthcare professionals' attitudes toward
      patients with substance use disorders, but few studies have specifically looked
      at emergency department (ED) physicians. Individuals with substance use disorders
      are more likely to be people who chronically, frequently use the ED, and thus ED
      physicians are in a unique position to provide early identification and
      intervention for people struggling with addiction. The purpose of this study was
      to understand ED physicians' attitudes toward patients with substance use
      disorder with the aim of decreasing stigma and improving the care of ED patients
      with substance use disorder. METHODS: An anonymous Qualtrics survey was emailed
      to 115 emergency physicians in the Johns Hopkins Health System. The survey
      contained (1) demographics and (2) the medical condition regard scale,
      http://links.lww.com/JAM/A67. Participants were offered a $10 Amazon gift card to
      complete the survey. RESULTS: The response rate was 50% (n = 58) and the
      completion rate was 43% (n = 50). Physicians had lower regard for patients with
      substance use disorders than other medical conditions with behavioral components.
      Of note, 54% of respondents indicated that they at least "somewhat agree" that
      they "prefer not to work with patients with substance use who have pain."
      CONCLUSIONS: A significant portion of our study population had low regard for
      patients with substance use. Future research is needed to determine significant
      contributing factors and develop interventions to mitigate negative attitudes
      among ED physicians toward patients with substance use disorder.

PMID- 29351142
TI  - Worldwide end-of-life practice for patients in ICUs.
AB  - PURPOSE OF REVIEW: Published data and practice recommendations on end-of-life
      (EOL) generally reflect Western practice frameworks. Understanding worldwide
      practices is important because improving economic conditions are promoting rapid
      expansion of intensive care services in many previously disadvantaged regions,
      and increasing migration has promoted a new cultural diversity previously
      predominantly unicultural societies. This review explores current knowledge of
      similarities and differences in EOL practice between regions and possible causes
      and implications of these differences. RECENT FINDINGS: Recent observational and
      survey data shows a marked variability in the practice of withholding and
      withdrawing life sustaining therapy worldwide. Some evidence supports the view
      that culture, religion, and socioeconomic factors influence EOL practice, and
      individually or together account for differences observed. There are also likely
      to be commonly desired values and expectations for EOL practice, and recent
      attempts at establishing where worldwide consensus may lie have improved our
      understanding of shared values and practices. SUMMARY: Awareness of differences,
      understanding their likely complex causes, and using this knowledge to inform
      individualized care at EOL is likely to improve the quality of care for patients.
      Further research should clarify the causes of EOL practice variability, monitor
      trends, and objectively evaluate the quality of EOL practice worldwide.

PMID- 29351143
TI  - Nutrition in the ICU: new trends versus old-fashioned standard enteral feeding?
AB  - PURPOSE OF REVIEW: The narrative review aims to summarize the relevant studies
      from the last 2 years and provide contextual information to understand findings.
      RECENT FINDINGS: Recent ICU studies have provided insight in the pathophysiology
      and time course of catabolism, anabolic resistance, and metabolic and endocrine
      derangements interacting with the provision of calories and proteins.Early
      provision of high protein intake and caloric overfeeding may confer harm.
      Refeeding syndrome warrants caloric restriction and to identify patients at risk
      phosphate monitoring is mandatory.Infectious complications of parenteral
      nutrition are associated with overfeeding. In recent studies enteral nutrition is
      no longer superior over parenteral nutrition.Previously reported benefits of
      glutamine, selenium, and fish oil seem to have vanished in recent studies;
      however, studies on vitamin C, thiamine, and corticosteroid combinations show
      promising results. SUMMARY: Studies from the last 2 years will have marked impact
      on future nutritional support strategies and practice guidelines for critical
      care nutrition as they challenge several old-fashioned concepts.

PMID- 29351144
TI  - Cardiac dysfunction in critical illness.
AB  - PURPOSE OF REVIEW: Sepsis and septic shock are prevalent conditions that are
      likely to increase in prevalence in the future. Given the high mortality and
      morbidity associated with sepsis and sepsis-induced cardiac dysfunction, we must
      continue to make advances in knowledge of the complex physiologic interactions
      and how we may target specific mediators for potential therapeutic options in the
      future. RECENT FINDINGS: Multiple biomarkers have been discovered, which when
      assayed in sepsis-induced cardiomyopathy predict morbidity and mortality. With
      increased sensitivity of echocardiography, we can diagnose subclinical cardiac
      dysfunction, which may have future implications for slowing or preventing
      progressive dysfunction. SUMMARY: Sepsis-induced cardiomyopathy is the result of
      complicated interactions between the pathogen, the body's response to infection,
      and iatrogenic injury. Interplay between inflammatory, metabolic, and adrenergic
      systems results in direct and indirect myocardial injury leading to decreases in
      both systolic and diastolic cardiac function. As the interactions are further
      elucidated with additional research into other proteins and mediators, new
      treatment options can be researched. VIDEO ABSTRACT.

PMID- 29351147
TI  - Foreword.

PMID- 29351145
TI  - Recent evidence on early mobilization in critical-Ill patients.
AB  - PURPOSE OF REVIEW: To examine the benefits of early mobilization and summarize
      the results of most recent clinical studies examining early mobilization in
      critically ill patients followed by a presentation of recent developments in the
      field. RECENT FINDINGS: Early mobilization of ICU patients, defined as
      mobilization within 72 h of ICU admission, is still uncommon. In medical and
      surgical critically ill patients, mobilization is well tolerated even in
      intubated patients. In neurocritical care, evidence to support early mobilization
      is either lacking (aneurysmal subarachnoid hemorrhage), or the results are
      inconsistent (e.g. stroke). Successful implementation of early mobilization
      requires a cultural change; preferably based on an interprofessional approach
      with clearly defined responsibilities and including a mobilization scoring
      system. Although the evidence for the majority of the technical tools is still
      limited, the use of a bed cycle ergometer and a treadmill with strap system has
      been promising in smaller trials. SUMMARY: Early mobilization is well tolerated
      and feasible, resulting in improved outcomes in surgical and medical ICU
      patients. Implementation of early mobilization can be challenging and may need a
      cultural change anchored in an interprofessional approach and integrated in a
      patient-centered bundle. Scoring systems should be integrated to define daily
      goals and used to verify patients' achievements or identify barriers immediately.

PMID- 29351150
TI  - Foreword.

PMID- 29351148
TI  - Women's Health Outpatient Care Teams: Focus on Advanced Practice Providers.
AB  - Team-based care in the outpatient women's health setting has the potential to
      help alleviate the demand for women's health care providers and to deliver
      improved quality of care to the growing population of US women. Although teamwork
      is necessary in the current health care system, most of the current obstetrics
      and gynecology and advanced practice provider (APP) workforce were not trained
      for collaborative practice. Core competencies for building an effective
      outpatient women's health care team are explained and current evidence regarding
      the specific role of APPs in women's health care is reviewed.

PMID- 29351151
TI  - Hepatitis C in Pregnancy in the Era of Direct-acting Antiviral Treatment:
      Potential Benefits of Universal Screening and Antepartum Therapy.
AB  - Hepatitis C in pregnancy is on the rise, and new direct-acting antiviral agents
      are available that cure the disease. Published recommendations need to be
      reviewed and clinically evaluated for the care of pregnant women who are at risk
      for or have chronic hepatitis C. Available evidence and some of the medical and
      ethical reasons to consider universal screening and antepartum therapy for
      hepatitis C during pregnancy are presented. Universal screening and proactive
      treatment during pregnancy is on the horizon, and these measures should be
      quickly evaluated for safety and implemented if appropriate.

PMID- 29351152
TI  - Ebola Infection in Pregnancy: A Global Perspective and Lessons Learned.
AB  - The 2014 to 2016 Ebola outbreak, primarily based in 3 West African countries, had
      far-reaching global effects. Importantly, the crisis highlighted large gaps in
      reproductive health services in affected countries and inadequate health care
      system preparedness for obstetrical patients in the setting of highly contagious
      infectious diseases. We aim to review Ebola virus effects with a focus on the
      obstetrical implications in the context of this recent Ebola outbreak, discuss
      the lessons learned following this outbreak and propose current measures specific
      to obstetrics that should be considered in preparation for the next concerning
      emergent infectious disease.

PMID- 29351154
TI  - Predictors of Health-related Quality of Life in Irritable Bowel Syndrome Patients
      Compared With Healthy Individuals.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) reduces health-related quality of life
      (HRQOL). It is unclear how having IBS modifies the impact of gastrointestinal
      (GI), psychosocial, and somatic symptom variables on HRQOL compared with healthy
      controls (HCs). AIMS: (1) Determine psychosocial, somatic, and physical status
      variables most predictive of HRQOL in IBS and HCs and (2) determine if IBS status
      modifies relationships between predictive factors and HRQOL. METHODS: IBS
      patients and HCs completed validated questionnaires measuring GI symptoms,
      psychosocial/somatic variables, and physical [physical component score (PCS)] and
      mental [mental component score (MCS)] HRQOL via the Short-Form-36. Associations
      between these variables and HRQOL were evaluated with multiple linear
      regressions. Variables were standardized to determine the strongest predictors of
      HRQOL. Statistical significance level was 0.01. RESULTS: Mean HRQOL was higher in
      417 HCs versus 290 IBS subjects (PCS: 55.6 vs. 48.6, P<0.001; MCS: 53.7 vs. 44.8,
      P<0.001). The GI symptom measures were negatively associated with PCS in IBS, but
      only usual severity was associated with MCS (P<0.01). In all subjects,
      psychosocial and somatic measures were associated with MCS and not PCS excluding
      GI symptom anxiety, which correlated with both (P<0.01). The strongest predictor
      of MCS was perceived stress in IBS and depression symptoms in HCs. GI symptom
      anxiety was the strongest predictor of PCS in both. Greater perceived stress and
      somatic symptom severity and less mindfulness was linked to larger reductions in
      HRQOL for IBS compared with HCs (P<0.01). CONCLUSIONS: GI symptom severity and
      anxiety correlate with PCS, whereas psychosocial/somatic measures parallel MCS.
      However, HRQOL is comparable in IBS and HCs when perceived stress, somatic
      symptom severity, and mindfulness are at optimal levels. These findings may have
      important implications in the management of IBS.

PMID- 29351155
TI  - Inpatient Outcomes for Gastrointestinal Bleeding Associated With Percutaneous
      Coronary Intervention.
AB  - GOALS: The goal of this study was to evaluate the impact of inpatient outcomes of
      gastrointestinal bleeding (GIB) related to percutaneous coronary intervention
      (PCI). BACKGROUND: With all-cause mortality increasing in patients undergoing
      PCIs, outcomes for GIB associated with PCI may be adversely impacted. STUDY:
      Using the National Inpatient Sample (2007 to 2012), we performed a nested case
      control study assessing inpatient outcomes including incidence and mortality for
      PCI-related GIB hospitalizations. Multivariate logistic regression analyses were
      performed to determine significant predictors for GIB incidence and mortality.
      RESULTS: A total of 9332 (1.2%) of PCI hospitalizations were complicated by GIB
      with the age-adjusted incidence rate increasing 13% from 2007 (11.3 GIB per 1000
      PCI) to 2012 (12.8). Patients >=75 years of age experienced the steepest incline
      in GIB incidence, which increased 31% during the study period. Compared with non
      GIB patients, mean length of stay (9.4 d vs. 3.3 d) and median cost of care
      ($29,236 vs. $17,913) was significantly higher. Significant demographic risk
      factors for GIB included older age and comorbid risk factors included gastritis
      or duodenitis, and Helicobacter pylori infection.In total, 1044 (11%) of GIB
      patients died during hospitalization with the GIB mortality rate increasing 30%
      from 2007 (95 deaths per 1000 GIB) to 2012 (123). Older age had the strongest
      association with inpatient mortality. CONCLUSIONS: Inpatient incidence and
      mortality for PCI-related GIB has been increasing particularly with a large
      increase in incidence among older patients. A multidisciplinary approach focused
      on risk-stratifying patients may improve preventable causes of GIB.

PMID- 29351156
TI  - Liquid Nitrogen Spray Cryotherapy is Associated With Less Postprocedural Pain
      Than Radiofrequency Ablation in Barrett's Esophagus: A Multicenter Prospective
      Study.
AB  - GOALS AND BACKGROUND: Two common endoscopic therapies for eradication of
      dysplastic Barrett's esophagus are radiofrequency ablation (RFA) and liquid
      nitrogen spray cryotherapy (LNC). There is no data comparing postprocedural pain.
      This study aimed to compare the incidence of postprocedural pain between the 2
      ablation modalities. METHODS: This is a multicenter prospective study in which
      pain intensity scores and the presence of dysphagia were assessed immediately
      before and after treatment, 48 hours posttreatment and at 3 weeks posttreatment
      using validated instruments. RESULTS: Of 94 patients, 35 underwent LNC and 59
      underwent RFA [36 with focal radiofrequency ablation (RFA-F) and 23 with
      circumferential radiofrequency ablation (RFA-C)]. Immediately posttreatment,
      patients in the LNC group reported an average Numeric Pain Scale score that was
      lower than in the RFA groups [LNC 0.41 vs. RFA-F 1.18 (P=0.026), LNC 0.41 vs. RFA
      C 1.38 (P=0.010)]. These differences persisted at 48 hours posttreatment [LNC
      0.76 vs. RFA-F 1.77 (P=0.013), LNC 0.76 vs. RFA-C 1.73 (P=0.018)]. The odds of
      pain after RFA were at least 5 times greater than after LNC [immediately
      posttreatment odds ratio, 5.26 (95% confidence interval, 1.85-14.29) and 48 h
      posttreatment odds ratio, 5.56 (95% confidence interval, 2.27-14.29)]. There was
      no difference in dysphagia after treatment in either group, at any time point
      (P=0.429). CONCLUSION: LNC was associated with less postprocedural pain when
      compared with RFA. These results help inform patients and physicians about the
      expected symptoms after ablative endotherapy.

PMID- 29351157
TI  - Association Between Cotinine-verified Smoking Status and Risk of Colorectal
      Neoplasia.
AB  - GOALS: We evaluated the association of urinary cotinine-verified smoking status
      with the risk of colorectal neoplasia (CRN). BACKGROUND: Many studies have
      reported the association between the risk of CRN and smoking status, based on
      self-reported questionnaires. Although self-reported smoking status may be
      inaccurate, to our knowledge, no study has yet assessed the association between
      objective biomarkers of tobacco exposure and the risk of CRN. STUDY: A cross
      sectional study was conducted on 96,806 asymptomatic examinees who underwent
      colonoscopy and urinary cotinine measurements as part of a health check-up.
      Cotinine-verified current smokers were participants having a urinary cotinine
      level >=50 ng/mL. RESULTS: The mean participant age was 38.4 years, and the
      proportion of cotinine-verified current smokers was 23.0%. Cotinine-verified
      current smoking was an independent risk factor for CRN [adjusted odds ratio
      (AOR), 1.49; 95% confidence interval (CI), 1.42-1.56] and advanced CRN (ACRN)
      (AOR, 1.79; 95% CI, 1.57-2.05). Moreover, the risk of CRN and ACRN increased with
      increasing cotinine levels. Among self-reported never smokers, cotinine-verified
      current smokers had a higher risk of CRN (AOR, 1.77; 95% CI, 1.57-2.00) and ACRN
      (AOR, 1.94; 95% CI, 1.37-2.74) than cotinine-verified never smokers did, whereas
      among self-reported current smokers, cotinine-verified never smokers had a lower
      risk of CRN (AOR, 0.78; 95% CI, 0.70-0.87) and ACRN (AOR, 0.71; 95% CI, 0.52
      0.98) than cotinine-verified current smokers did. CONCLUSIONS: Cotinine-captured
      smoking status and metabolic variation exhibit associations with CRN more
      accurately and objectively than self-reporting does, providing clearer evidence
      for the role of tobacco in the development of CRN.

PMID- 29351158
TI  - Physical Performance Measures of Flexibility, Hip Strength, Lower Limb Power and
      Trunk Endurance in Healthy Navy Cadets: Normative Data and Differences Between
      Sex and Limb Dominance.
AB  - The objectives were to provide normative data on commonly used physical
      performance tests that may be associated with musculoskeletal injuries in Navy
      cadets, and assess for sex and limb dominance differences. A large cohort of Navy
      cadets were assessed for physical performance tests of flexibility (ankle
      dorsiflexion range of motion and sit and reach), isometric hip strength, lower
      limb power (single leg hop), and trunk endurance (plank and side plank tests).
      Besides providing normative data tables, sex and limb dominance differences were
      assessed by a two-way mixed ANOVA. A total of 545 Brazilian Navy cadets (394
      males) representing 79% of the cadets in the Academy participated. Normative
      reference values were reported as mean+/-SD, 95%CI and percentiles. For tests of
      muscle strength, power and endurance, males performed better than females
      (p<0.001). For flexibility tests, females achieved greater distances than males
      for the sit and reach test (p<0.001), but no difference for ankle dorsiflexion
      (p=0.51). Overall, there were no clinically relevant differences between limbs.
      In conclusion, normative data for commonly used physical performance tests were
      provided. Although no clinically relevant side-to-side differences were found,
      males presented higher values for lower limb strength and power, as well as trunk
      endurance than females, while females demonstrated increased flexibility.
      Valuable normative data are provided to professionals who work with young, active
      populations from the injury prevention or rehabilitation perspective; as the
      current study may help professionals to identify athletes or cadets whose
      performance is outside the normative values and may be at risk for injury.

PMID- 29351159
TI  - The Physical Characteristics by Sex and Age for Custody Assistants from a Law
      Enforcement Agency.
AB  - Custody assistants (CAs) are a position within a law enforcement agency who are
      responsible for assisting officers with maintaining security in correctional
      facilities. Unlike other positions, CAs may not be required to complete physical
      testing prior to being hired. This lack of testing could influence the
      characteristics of CAs who attend academy training. Therefore, retrospective
      analysis of performance test data for 108 officers (69 males, 39 females) was
      conducted. The tests included: grip strength for both hands; number of push-ups
      and sit-ups in 60 seconds; 201 m (220 yard) and 2.4 km runs; and maximal aerobic
      capacity (VO2max) estimated from the 2.4 km run. Data were stratified by sex and
      age (<=24 years, 25-29 years, 30-34 years, >=35 years). Independent samples t
      tests (p < 0.05) calculated differences between males and females. To compare age
      groups, a one-way ANOVA with Bonferroni post hoc was utilized (p < 0.05). Males
      scored significantly higher than females in hand grip, push-ups, and sit-ups,
      were faster over the 201 m and 2.4 km runs, and had a higher VO2max (p <= 0.001
      0.024). There were no significant differences in performance tests across the age
      groups for either males or females. To better tolerate the rigors of physical
      training, female CAs should attempt to improve their fitness prior to academy as
      they often need to complete the same tasks as the males. Age did not appear to
      influence the physical characteristics of CAs, although all CAs should attempt to
      develop the fitness qualities needed for their occupation.

PMID- 29351160
TI  - Acute Cardiorespiratory and Metabolic Effects of a Sandbag Resistance Exercise
      Protocol.
AB  - Ratamess, NA, Kang, J, Kuper, JD, O'Grady, EA, Ellis, NL, Vought, IT, Culleton,
      E, Bush, JA, and Faigenbaum, AD. Acute cardiorespiratory and metabolic effects of
      a sandbag resistance exercise protocol. J Strength Cond Res 32(6): 1491-1502,
      2018-The purpose of this study was to examine the acute cardiorespiratory and
      metabolic effects of a sandbag (SB) resistance exercise protocol and compare the
      responses to time-matched treadmill running protocols. Eight healthy, resistance
      trained men (21.1 +/- 1.0 years; 86.1 +/- 7.8 kg) completed 4 protocols of equal
      duration in random sequence: (a) SB, (b) treadmill running at 60% of V[Combining
      Dot Above]O2 reserve (60V[Combining Dot Above]O2R), (c) treadmill running at 80%
      of V[Combining Dot Above]O2 reserve (80V[Combining Dot Above]O2R), and (d) a
      control protocol. The SB protocol was 16 minutes in duration and consisted of 3
      circuits of 8 multiple-joint exercises (with 11-, 20-, or 48-kg SBs) performed
      for as many repetitions as possible for 20 seconds followed by a 10-second rest
      interval before beginning the next exercise. Two minutes of rest was allowed
      between circuits. Breath-by-breath oxygen consumption (V[Combining Dot Above]O2)
      and heart rate (HR) were recorded throughout each protocol and for 30 minutes
      postexercise (PE) and blood lactate was determined before and immediately after
      each protocol. Blood lactate was significantly higher after SB compared with
      60V[Combining Dot Above]O2R and 80V[Combining Dot Above]O2R. Mean and peak HR in
      SB was significantly higher than 60V[Combining Dot Above]O2R but not different
      from 80V[Combining Dot Above]O2R. Mean V[Combining Dot Above]O2 and energy
      expenditure (EE) in SB was significantly lower than 60V[Combining Dot Above]O2R
      and 80V[Combining Dot Above]O2R during each protocol but significantly higher
      after SB compared with 60V[Combining Dot Above]O2R and 80V[Combining Dot
      Above]O2R PE. Compared with 60V[Combining Dot Above]O2R and 80V[Combining Dot
      Above]O2R, respiratory exchange ratio was significantly higher during SB and
      through 5 minutes PE, but was significantly lower at 25-30 minutes PE after SB.
      Sandbag, as performed in this study, provides a superior metabolic stimulus to
      treadmill running during the PE period; however, the SB results demonstrate
      inferior EE compared with running at 60V[Combining Dot Above]O2R and
      80V[Combining Dot Above]O2R.

PMID- 29351161
TI  - Effects of Contrast Strength vs. Plyometric Training on Lower Limb Explosive
      Performance, Ability to Change Direction and Neuromuscular Adaptation in Soccer
      Players.
AB  - The aim was to compare the effects of two differing 8-week in-season strength
      training programs (contrast strength training [CST] vs. plyometric training [PT])
      on selected performance tests (5 and 40m sprints, S 4 X 5 m change of direction
      test, squat (SJ) and countermovement (CMJ) jumps , leg peak power on a cycle
      ergometer force-velocity test, 1-repetition maximal (1-RM) half squat, and
      electromyographic [EMG] activity of the vastus lateralis, vastus medialis and
      rectus femoris muscles during vertical jump tests). Forty male soccer players
      (age = 15.8 +/- 0.4 years; body mass = 58.8 +/- 6.3 kg; body height = 1.74 +/-
      0.06 m; body fat = 10.5 +/- 1.9 %) were divided between a contrast strength (CSG,
      n = 14), plyometric (PG, n = 14) and control groups (CG, n = 12). Both training
      programs enhanced sprint performance (p<0.001 in 5m; p<=0.05 in 40m) and change
      of direction test scores (p<0.001) relative to controls. PG and CSG increased SJ
      height relative to the CG, with a slightly greater response in CSG compared to PG
      (p<=0.05). The majority of CMJ scores increased significantly in both CSG and PG
      relative to the CG, with no inter-group differences in training response. The
      majority of force-velocity scores increased significantly in the CSG relative to
      PG and CG. The EMG parameters also increased in the CSG relative to both PG and
      CG. In summary, most measures of athletic performance in male soccer players were
      enhanced after CST and PT. However, the improvement of physical performance was
      better with eight weeks of CST than with PT. Thus, coaches should be encouraged
      to include CST as an element of in-season conditioning.

PMID- 29351162
TI  - Potentiation Effects of the French Contrast Method on Vertical Jumping Ability.
AB  - Hernandez-Preciado, JA, Baz, E, Balsalobre-Fernandez, C, Marchante, D, and Santos
      Concejero, J. Potentiation effects of the French contrast method on the vertical
      jumping ability. J Strength Cond Res 32(7): 1909-1914, 2018-This study examined
      the acute effects of the potentiation protocol known as French Contrast Method on
      the vertical jumping ability measured using a countermovement jump (CMJ). Thirty
      one athletes participated in this study (intervention group n = 17 and control
      group n = 14). The CMJ height was measured using the iOS application My Jump 2.0
      before and after the French Contrast protocol, which consisted of 3 sets of
      isometric partial squats, drop jumps, dynamic half-squats, and hurdle jumps. The
      CMJ height improved from its baseline values by 5.1 +/- 1.1% (p < 0.001, effect
      size [ES] = 0.27) after the first set, by 6.8 +/- 1.8% (p < 0.001, ES = 0.41)
      after the second set, and by 8.5 +/- 2.9% (p < 0.001, ES = 0.44) after the third
      set. The maximal potentiation value was an increase of 11 +/- 6.3% (p < 0.001).
      The control group decreased its CMJ height from the baseline levels, reaching a
      significant decrement of -2.1 +/- 1.6% (p = 0.047). These findings suggest that
      the French Contrast Method is a valid strategy to improve the vertical jumping
      ability. This method can be used after the warm-up as a conditioning activity to
      acutely enhance the lower body's force and power production.

PMID- 29351163
TI  - Comparison of the Force-, Velocity- and Power-Time Curves Between the Concentric
      Only and Eccentric-Concentric Bench Press Exercises.
AB  - The aim of this study was to compare the temporal and mechanical variables
      between the concentric-only and eccentric-concentric bench press (BP) variants.
      Twenty-one men (age: 22.0+/-4.2 years, body mass: 73.4+/-7.7 kg, height: 177.2+/
      8.0 cm; one-repetition maximum [1RM]: 1.12+/-0.12 kg?kg) were evaluated during
      the concentric-only and eccentric-concentric BP variants using 80% 1RM. Temporal
      (concentric phase duration, propulsive phase duration, and time to reach the
      maximum values of force, velocity, and power) and mechanical variables (force,
      velocity, and power), determined using a linear velocity transducer, were
      compared between both BP variants. All temporal variables were significantly
      lower during the eccentric-concentric BP compared to the concentric-only BP (P <
      0.05; effect size [ES] range: 0.80-2.52). Maximum force as well as the mean
      values of velocity and power were significantly higher for the eccentric
      concentric BP compared to the concentric-only BP (all P < 0.001; ES range: 2.87
      3.58). However, trivial to small differences between both BP variants were
      observed for mean force (ES: 0.00-0.36) as well as for maximum velocity (ES:
      0.40) and power (ES: 0.41). The stretch-shortening cycle (i.e., eccentric
      concentric BP) mainly enhanced force production at the early portion of the
      concentric phase, but this potentiation effect gradually reduced over the latter
      part of the movement. Finally, force was higher for the concentric-only BP during
      49% of the concentric phase duration. These results suggest that both BP variants
      should be included during resistance training programs in order to optimize force
      output at different points of the concentric phase.

PMID- 29351164
TI  - Body Mass Index Versus Body Fat Percentage in Prospective National Football
      League Athletes: Overestimation of Obesity Rate in Athletes at the National
      Football League Scouting Combine.
AB  - Provencher, MT, Chahla, J, Sanchez, G, Cinque, ME, Kennedy, NI, Whalen, J, Price,
      MD, Moatshe, G, and LaPrade, RF. Body mass index versus body fat percentage in
      prospective national football league athletes: overestimation of obesity rate in
      athletes at the national football league scouting combine. J Strength Cond Res
      32(4): 1013-1019, 2018-Obesity has been previously noted as a major issue in the
      National Football League (NFL), where it has been shown that 97% of all players
      demonstrate a body mass index (BMI) of >=25.0 with a reported obesity rate of 56%
      (BMI >= 30.0). However, BMI does not take into account body composition by mass,
      and may overestimate prevalence of obesity. The purposes of this study were (a)
      to determine the validity of BMI as a measure of body fat percentage and obesity
      in athletes at the NFL Combine, (b) to define the obesity rate based on body fat
      percentage compared with BMI, and (c) to determine the relationship between draft
      status and body composition. It was hypothesized that the rate of obesity, as
      measured by air displacement plethysmography (ADP), would be less than the rate
      of obesity as measured using BMI. Athletes who competed at the 2010 through 2016
      NFL Combines were included in this study. Air displacement plethysmograph testing
      at the Combine was performed through BOD POD Body Composition Tracking System
      with collection of the following metrics: body fat percentage (%), and compared
      with BMI based on weight and height. In addition, the metrics were evaluated for
      differences over the 7-year study period to determine temporal changes and to
      determine draft status based on position relative to BOD POD calculations. A
      total of 1,958 NFL Combine participants completed ADP body composition testing.
      Based on BMI (>=30.0), the obesity rate was 53.4% versus an 8.9% obesity rate
      when using ADP. Drafted players demonstrated a significantly lower body fat
      percentage than undrafted players (p <= 0.05), with the exception of quarterbacks
      and running backs. All 8 positions of play, with the exception of defensive
      linemen, demonstrated a decrease in body fat percentage between 2010 and 2017.
      However, total body mass by position of play remained relatively constant with no
      significant change noted in any position. In conclusion, the obesity rate in
      prospective athletes at the NFL Combine was overestimated when calculated based
      on the BMI. Body fat percentage was more valid for determining an NFL player
      candidate's true body composition. Drafted players demonstrated a significantly
      lower body fat percentage in 6 of 8 positions compared with undrafted players.
      This is important to recognize for a strength and conditioning professional to
      use the correct metric when evaluating NFL players who could have been
      erroneously categorized in the obese population by their BMI. Furthermore, a
      higher percentage of fat translates to lower chances of becoming drafted.

PMID- 29351165
TI  - Relationship Between Maximum Pull-up Repetitions and First Repetition Mean
      Concentric Velocity.
AB  - Beckham, GK, Olmeda, JJ, Flores, AJ, Echeverry, JA, Campos, AF, and Kim, SB.
      Relationship between maximum pull-up repetitions and first repetition mean
      concentric velocity. J Strength Cond Res 32(7): 1831-1837, 2018-Mean concentric
      velocity (MCV) of exercise execution has been used by strength and conditioning
      professionals to improve exercise technique, provide accurate feedback, and
      predict exercise 1 repetition maximum. There is still limited research on
      velocity-based training and currently only one research study on the pull-up
      exercise. The primary purpose of this research was to determine whether the
      maximum number of pull-ups an individual can perform can be predicted by the MCV
      of a single pull-up repetition. Forty-nine healthy men and women were recruited
      who reported they could do at least 2 pull-ups. Each subject performed a
      standardized warm-up, then a single pull-up repetition, followed by one set of
      pull-up repetitions to failure. The GymAware PowerTool, a linear position
      transducer, was used to measure the MCV of each pull-up repetition. Both the MCV
      of the single repetition and first repetition of the set to failure were
      recorded, and the greater of the 2 was used in later analysis. Weighted least
      squares linear regression was used to estimate the relationship between the
      single-repetition MCV and maximum amount of pull-up repetitions. We observed a
      statistically significant linear relationship between the maximum number of pull
      ups and the MCV of a single pull-up repetition (y = -6.661 + 25.556x, R = 0.841).
      Prediction of the maximum pull-up number by a single repetition rather than
      testing the maximal pull-up number may improve efficiency and effectiveness of
      exercise testing batteries for military, police, and other populations.

PMID- 29351167
TI  - Can Caffeine Intake Improve Neuromuscular and Technical-Tactical Performance
      During Judo Matches?
AB  - This study aimed to verify the effect of caffeine intake on blood lactate
      concentrations and neuromuscular and technical-tactical performance during
      simulated judo matches. Fourteen male judo athletes received capsules containing
      caffeine or placebo and were evaluated in both conditions. Before the baseline
      and 1 hour after the caffeine/placebo intake, athletes performed the
      countermovement jump test (CMJ), handgrip strength, judogi grip strength test
      (JGST), and blood samples were collected. Subsequently, the athletes were
      submitted to three 5 minute matches with 15 minute intervals. All neuromuscular
      tests were performed and blood samples were taken during the matches' intervals.
      Significant interaction between condition and time (p = 0.01) was found for blood
      lactate concentrations. No interaction between condition and time was verified
      for CMJ performance (p > 0.05), handgrip strength (p > 0.05), JGST performance (p
      = 0.32) and number of attacks (p = 0.97). However, for all variables a
      significant decrease was observed throughout time (p < 0.05). According to
      clinical results (magnitude-based inference), we identified post-match 2 and post
      match 3 showed higher effect (most likely positive effect) regarding delta
      caffeine - placebo than other moments (pre-match and post-match 1) for blood
      lactate. Caffeine increased the estimated glycolytic contribution over the
      matches; however, it did not induce improvements in neuromuscular performance or
      number of attacks.

PMID- 29351166
TI  - Neuromuscular, Biochemical, Endocrine, and Mood Responses to Small-Sided Games'
      Training in Professional Soccer.
AB  - William, S, Turner, AN, Weston, M, Russell, M, Johnston, MJ, and Kilduff, LP.
      Neuromuscular, biochemical, endocrine, and mood responses to small-sided games'
      training in professional soccer. J Strength Cond Res 32(9): 2569-2576, 2018-The
      24-hour responses to small-sided games' (SSGs) soccer training were
      characterized. Professional soccer players (n = 16) performed SSG's (4vs4 +
      goalkeepers; 6 * 7-minutes, 2-minute interset recovery) with performance (peak
      power output [PPO] and jump height [JH]), physiological (blood creatine kinase
      [CK], lactate, salivary testosterone, and cortisol), and mood measures collected
      before (baseline), and after (immediately; 0, +2, and +24 hours). For PPO and JH,
      possibly small-moderate reductions occurred at 0 hour (-1.1 W.kg; +/-0.9 W.kg, 
      3.2 cm; +/-1.9 cm, respectively), before returning to baseline at +2 hours
      (trivial), and declining thereafter (small-moderate effect) at +24 hours (-0.9
      W.kg; +/-0.8 W.kg, -2.5 cm; +/-1.2 cm, respectively). Lactate increased at 0
      hours (likely large; +1.3 mmol.L; +/-0.5 mmol.L), reduced at +2 hours (likely
      small; -0.5 mmol.L; +/-0.2 mmol.L), and returned to baseline at 24 hours
      (trivial). A very likely small increase in CK occurred at 0 hour (+97 MU.L; +/-28
      MU.L), persisting for +24 hours (very likely small; +94 MU.L; +/-49 MU.L).
      Possibly small increases in testosterone (+20 pg.ml; +/-29 pg.ml) occurred at 0
      hour, before likely moderate declines at +2 hours (-61 pg.ml; +/-21 pg.ml)
      returning to baseline at +24 hours (trivial). For cortisol, possibly small
      decreases occurred at 0 hour (-0.09 MUg.dl; +/-0.16 MUg.dl), before likely large
      decreases at +2 hours (-0.39 MUg.dl; +/-0.12 MUg.dl), which persisted for 24
      hours (likely small; -0.12 MUg.dl; +/-0.11 MUg.dl). Mood was disturbed by SSG's
      at 0 hour (likely moderate; +13.6 AU, +/-5.6 AU) and +2 hours (likely small; +7.9
      AU; +/-5.0 AU), before returning to baseline at +24 hours (trivial). The movement
      demands of SSG's result in a bimodal recovery pattern of neuromuscular function
      and perturbations in physiological responses and mood for up to 24 hours.
      Accordingly, when programming soccer training, SSG's should be periodized
      throughout the competitive week with submaximal technical/tactical activities.

PMID- 29351168
TI  - Coregulation of endoplasmic reticulum stress and oxidative stress in neuropathic
      pain and disinhibition of the spinal nociceptive circuitry.
AB  - The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum
      (ER) lumen leads to ER stress, which is related to cellular reactive oxygen
      species production. Neuropathic pain may result from spinal dorsal horn (SDH) ER
      stress. In this study, we examined the cause-effect relationship between ER
      stress and neuropathic pain using the spinal nerve ligation (SNL) rat model. We
      showed that ER stress was mutually promotive with oxidative stress during the
      process. We also tested the hypothesis that spinal sensitization arose from
      reduced activities of GABA-ergic interneurons and that spinal sensitization was
      mediated by SDH ER stress. Other important findings in this study including the
      following: (1) nociceptive behavior was alleviated in SNL rat as long as
      tauroursodeoxycholic acid injections were repeated to inhibit ER stress; (2)
      inducing SDH ER stress in healthy rat resulted in mechanical hyperalgesia; (3)
      blocking protein disulfide isomerase pharmacologically reduced ER stress and
      nociceptive behavior in SNL rat; (4) cells in the dorsal horn with elevated ER
      stress were mainly neurons; and (5) whole-cell recordings made in slide
      preparations revealed significant inhibition of GABA-ergic interneuron activity
      in the dorsal horn with ER stress vs in the healthy dorsal horn. Taken together,
      results of the current study demonstrate that coregulation of ER stress and
      oxidative stress played an important role in neuropathic pain process. Inhibiting
      SDH ER stress could be a potential novel strategy to manage neuropathic pain.

PMID- 29351169
TI  - Professionals underestimate patients' pain: a comprehensive review.
AB  - Pain assessment by patients is the rule in clinical trials but may not be in
      clinical practice. We examined studies comparing assessment of pain by patients
      and professionals in clinical practice using published studies (1990-2016; >=20
      patients), in English, in an institutional setting, comparing pain assessment
      within 24 hours by patients and health care professionals. A difference of at
      least 10% of the maximum score was considered significant. We judged quality on
      sampling method, blinding, and study size. Eighty studies (20,496 patients)
      provided data from a range of settings and locations; most (51%) used unbiased
      sampling, and most (68%) were blind or probably blind. Nine studies with >=500
      patients involved 58% of patients; 60 with <200 patients involved 25%. Large
      studies were more likely to use comprehensive or random sampling and blinding of
      patients and professionals. Underestimation of pain by professionals compared
      with patients was reported by 62/80 studies (78%); there was no difference in 17
      (21%) and overestimation in 1 (1%). Underestimation was reported in 75% of large
      studies (>500 patients), 91% of mid-sized studies (200-400), and 78% of small
      studies (<200). High-quality studies (blind, comprehensive, or random sampling,
      >200 patients) consistently reported underestimation (10/11; 91%). The extent of
      underestimation tended to increase with pain severity. Professionals consistently
      tend to underestimate pain compared with assessment by patients. This tendency is
      more pronounced with more severe pain, and the extent of underestimation can be
      large. It is likely that this contributes to undertreatment of pain.

PMID- 29351170
TI  - Risk of preterm birth following late pregnancy exposure to NSAIDs or COX-2
      inhibitors.
AB  - Pregnant women may take nonsteroidal antiinflammatory drugs (NSAIDs), selective
      cyclooxygenase (COX)-2 inhibitors, or biological agents to relieve symptoms or
      manage disease flares in late pregnancy. We aimed to quantify the risk of
      prematurity associated with late pregnancy exposure to nonselective NSAIDs,
      selective COX-2 inhibitors, and biological agents. Using data from Quebec
      Pregnancy Cohort, we performed a population-based cohort study. We included all
      women who were covered by the Quebec Drug Plan and had a singleton live birth
      between January 1, 1998 and December 31, 2009. Late pregnancy exposure was
      defined as having filled at least 1 prescription for nonselective NSAIDs,
      selective COX-2 inhibitors, or biological agents in the 3 months before delivery.
      Prematurity was defined as <37 weeks of gestation. Crude and adjusted odds ratios
      (OR) were obtained using generalized estimation equation models. Covariates
      included maternal autoimmune diseases, demographics, concomitant drug use,
      history of pregnancy complications, and other comorbidities. A total of 156,531
      pregnancies met inclusion criteria and were considered for analyses. In the 3
      months before delivery, 391 pregnancies were exposed to nonselective NSAIDs, 55
      to COX-2 inhibitors, and 12 to biological agents. After adjustment for maternal
      autoimmune diseases, concomitant medication use, and other risk factors, COX-2
      inhibitor use in late pregnancy was associated with a 2.46-fold increased risk of
      prematurity (adjusted OR, 2.46; 95% confidence interval, 1.28-4.72) compared to
      nonuse; only late pregnancy exposure to celecoxib was found to increase the risk
      (adjusted OR, 3.41; 95% confidence interval, 1.29-9.02). In conclusion, celecoxib
      use during late pregnancy may increase the risk of prematurity.

PMID- 29351171
TI  - Spinal PKC/ERK signal pathway mediates hyperalgesia priming.
AB  - Chronic pain can be initiated by one or more acute stimulations to sensitize
      neurons into the primed state. In the primed state, the basal nociceptive
      thresholds of the animal are normal, but in response to another hyperalgesic
      stimulus, the animal develops enhanced and prolonged hyperalgesia. The exact
      mechanism of how primed state is formed is not completely understood. Here we
      showed that spinal PKC/ERK signal pathway is required for neuronal plasticity
      change, hyperalgesic priming formation and the development of chronic
      hyperalgesia using acid-induced muscle pain (AIMP) model in mice. We discovered
      that pERK-positive neurons in the amygdala, spinal cord and dorsal root ganglion
      (DRG) were significantly increased after 1st acid injection. Inhibition of the
      pERK activity intrathecally, but not intracerebroventricularly or intramuscularly
      before 1st acid injection prevented the development of chronic pain induced by
      2nd acid injection which suggests hyperalgesic priming signal is stored at spinal
      cord level. Furthermore, intrathecal injection of PKC but not PKA blocker
      prevented the development of chronic pain and PKC agonist was sufficient to
      induce prolonged hyperalgesia response after acid injection. We also found that
      mTOR-dependent protein synthesis was required for the priming establishment. To
      test whether hyperalgesic priming leads to synaptic plasticity change, we
      recorded fEPSPs from spinal cord slices and found enhanced LTP in mice received
      one acid injection. This LTP enhancement was prevented by inhibition of ERK.
      These findings show that the activation of PKC/ERK signal pathway and downstream
      protein synthesis is required for hyperalgesic priming and the consolidation of
      pain singling.

PMID- 29351172
TI  - Systematic review and meta-analysis of genetic risk factors for neuropathic pain.
AB  - Neuropathic pain (NP) is an increasingly common chronic pain state and a major
      health burden, affecting approximately 7% to 10% of the general population.
      Emerging evidence suggests that genetic factors could partially explain
      individual susceptibility to NP and the estimated heritability in twins is 37%.
      The aim of this study was to systematically review and summarize the studies in
      humans that have investigated the influence of genetic factors associated with
      NP. We conducted a comprehensive literature search and performed meta-analyses of
      all the potential genetic variants associated with NP. We reviewed 29 full-text
      articles and identified 28 genes that were significantly associated with NP,
      mainly involved in neurotransmission, immune response, and metabolism. Genetic
      variants in HLA genes, COMT, OPRM1, TNFA, IL6, and GCH1, were found to have an
      association with NP in more than one study. In the meta-analysis, polymorphisms
      in HLA-DRB1*13 (odds ratio [OR], 2.96; confidence interval [CI], 1.93-4.56), HLA
      DRB1*04 (OR, 1.40; CI, 1.02-1.93), HLA-DQB1*03 (OR, 2.86; CI, 1.57-5.21), HLA
      A*33 (OR, 2.32; CI, 1.42-3.80), and HLA-B*44 (OR, 3.17; CI, 2.22-4.55) were
      associated with significantly increased risk of developing NP, whereas HLA-A*02
      (OR, 0.64; CI, 0.47-0.87) conferred reduced risk and neither rs1799971 in OPRM1
      (OR, 0.55; CI, 0.27-1.11) nor rs4680 in COMT (OR, 0.95; CI, 0.81-1.13) were
      significantly associated with NP. These findings demonstrate an important and
      specific contribution of genetic factors to the risk of developing NP. However,
      large-scale replication studies are required to validate these candidate genes.
      Our review also highlights the need for genome-wide association studies with
      consistent case definition to elucidate the genetic architecture underpinning NP.

PMID- 29351173
TI  - BSN Preparation for RNs: The Time Is Now!
AB  - Some nurse executives and academic nurse leaders believe that the issue of
      educational entry into professional nursing practice is an "old" issue. Nursing
      is the only healthcare profession that still does not require the minimum of a
      baccalaureate degree (BSN). It is time for nurse leaders to act: eliminate the
      multiple educational levels and require a minimum BSN degree for professional
      nurse practice.

PMID- 29351174
TI  - The Evolving Science of Patient and Family Engagement: An Interview With Dr Karen
      Drenkard.
AB  - Patient- and family-centered care is a central tenet of nursing practice. This
      concept has evolved to include patient partnerships, patient engagement, and
      patient activation. This column differentiates these concepts and describes the
      core principles embedded in the overriding intention of ensuring that patients
      (and their families or significant others) are orchestrators of their health and
      their care plans. In this interview, Karen Drenkard, PhD, RN, FAAN, NEA-BC, CNO,
      of the GetWellNetwork, discusses work by the O'Neil Center as a leader in this
      area.

PMID- 29351175
TI  - 2017 National Magnet Nurses of the Year(r).
AB  - The Magnet Recognition Program(r) recognizes healthcare organizations for quality
      patient care, nursing excellence, and innovations in professional nursing
      practice. Consumers rely on the Magnet designation as the ultimate credential for
      high-quality nursing. The ANCC National Magnet Nurse of the Year(r) awards were
      created in 2010 to recognize the outstanding contributions of clinical nurses for
      innovation, consultation, leadership, and professional risk taking.

PMID- 29351176
TI  - Technological Complexity and Emergence of the Entanglement.
AB  - As systems evolve over time, their natural tendency is to become increasingly
      more complex. Studies in the field of complex systems have generated new
      perspectives on the application of management strategies in health systems. Much
      of this research appears as a natural extension of the cross-disciplinary field
      of systems theory. This article is the 3rd in a series of articles that focus on
      why technological complexity is increasing and strategies nurse administrators
      can use to successfully implement change in the face of it.

PMID- 29351177
TI  - Units of Distinction: Creating a Blueprint for Recognition of High-Performing
      Medical-Surgical Nursing Units.
AB  - BACKGROUND: Hospital medical-surgical (M/S) nursing units are responsible for up
      to 28 million encounters annually, yet receive little attention from professional
      organizations and national initiatives targeted to improve quality and
      performance. OBJECTIVE: We sought to develop a framework recognizing high
      performing units within our large hospital system. METHODS: This was a
      retrospective data analysis of M/S units throughout a 168-hospital system.
      Measures represented patient experience, employee engagement, staff scheduling,
      nursing-sensitive patient outcomes, professional practices, and clinical process
      measures. RESULTS: Four hundred ninety units from 129 hospitals contributed
      information to test the framework. A manual scoring system identified the top 5%
      and recognized them as a "Unit of Distinction." Secondary analyses with machine
      learning provided validation of the proposed framework. CONCLUSIONS: Similar to
      external recognition programs, this framework and process provide a holistic
      evaluation useful for meaningful recognition and lay the groundwork for
      benchmarking in improvement efforts.

PMID- 29351178
TI  - Using Time-Referenced Data to Assess Medication Administration Performance and
      Quality.
AB  - OBJECTIVE: This study tests the feasibility of using a large (big) clinical data
      set to test the ability to extract time-referenced data related to medication
      administration to identify late doses and as-needed (PRN) administration patterns
      by RNs in an inpatient setting. METHODS: The study is a secondary analysis of a
      set of data using bar-code medication administration time stamps (n = 3043812)
      for 50883 patients admitted to a single, urban, 525-bed hospital in 11 inpatient
      units by 714 nurses between April 1, 2013, and March 31, 2015. RESULTS: The large
      majority of scheduled medications (43.3%) were administered between 9 to 10 AM
      and 9 to 10 PM accounting for the most amount of delayed doses. On average,
      patients received 8.9 medications per day, and nurses administered 19.7
      medications per shift. The average full-time nurse administered 3414 medications
      per year. CONCLUSIONS: The findings support use of time-referenced data to
      identify clinical processes and performance in administering scheduled and PRN
      medications.

PMID- 29351179
TI  - Measuring Care Coordination in the Pediatric Cardiology Ambulatory Setting.
AB  - The role of ambulatory nursing is diverse, and the impact on patient outcomes is
      difficult to measure. The concept of care coordination is an important focus for
      the ambulatory nurse. We describe the efforts to implement the Cardiac Care
      Coordination Measurement Tool to document and quantify care coordination
      activities in a pediatric cardiac ambulatory setting.

PMID- 29351180
TI  - One-Stage versus Two-Stage Repair of Asymmetric Bilateral Cleft Lip: A 20-Year
      Retrospective Study of Clinical Outcome.
AB  - BACKGROUND: Both one- and two-stage approaches have been widely used for patients
      with asymmetric bilateral cleft lip. There are insufficient long-term outcome
      data for comparison of these two methods. The purpose of this retrospective study
      was to compare the clinical outcome over the past 20 years. METHODS: The senior
      author's (L.J.L.) database was searched for patients with asymmetric bilateral
      cleft lip from 1995 to 2015. Qualified patients were divided into two groups: one
      stage and two-stage. The postoperative photographs of patients were evaluated
      subjectively by surgical professionals and laypersons. Ratios of the nasolabial
      region were calculated for objective analysis. Finally, the revision procedures
      in the nasolabial area were reviewed. Statistical analyses were performed.
      RESULTS: A total of 95 consecutive patients were qualified for evaluation.
      Average follow-up was 13.1 years. A two-stage method was used in 35 percent of
      the patients, and a one-stage approach was used in 65 percent. All underwent
      primary nasal reconstruction. Among the satisfaction rating scores, the one-stage
      repair was rated significantly higher than two-stage reconstruction (p = 0.0001).
      Long-term outcomes of the two-stage patients and the unrepaired mini-microform
      deformities were unsatisfactory according to both professional and
      nonprofessional evaluators. The revision rate was higher in patients with a
      greater-side complete cleft lip and palate as compared with those without palatal
      involvement. CONCLUSIONS: The results suggested that one-stage repair provided
      better results with regard to achieving a more symmetric and smooth lip and nose
      after primary reconstruction. The revision rate was slightly higher in the two
      stage patient group. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29351181
TI  - Cleft Palate Repair: Description of an Approach, Its Evolution, and Analysis of
      Postoperative Fistulas.
AB  - BACKGROUND: Fistulas following cleft palate repair impair speech, health, and
      hygiene and occur in up to 35 percent of cases. The authors detail the evolution
      of a surgical approach to palatoplasty; assess the rates, causes, and predictive
      factors of fistulas; and examine the temporal association of modifications to
      fistula rates. METHODS: Consecutive patients (n = 146) undergoing palatoplasty
      during the first 6 years of practice were included. The technique of repair was
      based on cleft type, and a common surgical approach was used for all repairs.
      RESULTS: The fistula rate was 2.4 percent (n = 125) after primary repair and 0
      percent (n = 21) after secondary repair. All complications occurred in patients
      with type III or IV clefts. Cleft width and cleft-to-total palatal width ratio
      were associated with fistulas, whereas syndromes, age, and adoption were not.
      Most complications could also be attributed to technical factors. During the
      first 2 years, modifications were made around specific anatomical features,
      including periarticular bony hillocks, maxillopalatine suture, velopalatine pits,
      and tensor insertion. The fistula rate declined by one-half in subsequent years.
      CONCLUSIONS: The authors describe a surgical approach to cleft palate repair, its
      evolution, and surgically relevant anatomy. Fistulas were associated with
      increasing cleft severity but could also be attributed to technical factors. A
      reduction in frequency and severity of fistulas was consistent with a learning
      curve and may in part be associated with modifications to the surgical approach.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29351182
TI  - The Management of Partial Zone II Intrasynovial Flexor Tendon Lacerations: A
      Literature Review of Biomechanics, Clinical Outcomes, and Complications.
AB  - BACKGROUND: Penetrating trauma or lacerations within zone II of the flexor sheath
      may result in partial tendon injury. The proper management of this injury is
      controversial; the literature contains differing indications for surgical
      treatment and postoperative rehabilitation. METHODS: A literature review of the
      Cochrane, MEDLINE, and PubMed databases was performed using the following search
      criteria: partial, flexor, tendon, and laceration. All English language studies
      that evaluated biomechanical strength, complications, and outcomes after partial
      tendon injury in human and animal studies were included and reviewed by two of
      the authors. RESULTS: Animal and cadaveric biomechanical studies have
      demonstrated that partial lacerations involving up to 95 percent of the tendon
      cross-sectional area can safely tolerate loads generated through unresisted,
      active finger flexion. Suture tenorrhaphy of partial tendon injury is associated
      with decreased tendon tensile strength, increased resistance, and decreased
      tendon gliding. Complications of nonsurgical management include triggering and
      entrapment, which can be managed by tendon beveling or pulley release. Late
      rupture is extremely uncommon (one report). CONCLUSIONS: Partial tendon
      lacerations involving 90 percent of the cross-sectional area can be safely
      treated without surgical repair and immediate protected active motion.
      Indications for exploration and treatment include concern for complete injury,
      triggering of the involved digit, or entrapment of the tendon. Surgical treatment
      for tendon triggering or entrapment with less than 75 percent cross-sectional
      injury is beveling of the tendon edges and injuries greater than 75 percent
      should be repaired with a noncircumferential, simple epitendinous suture. All
      patients should be allowed to perform early protected active motion after
      surgery.

PMID- 29351183
TI  - The Effect of Impactful Articles on Clinical Practice in the United States:
      Corticosteroid Injection for Patients with Lateral Epicondylitis.
AB  - BACKGROUND: Following publication of high-level evidence demonstrating that it is
      not an effective treatment for lateral epicondylitis, a reduction in the
      corticosteroid injection rate would be expected. The authors aimed to clarify
      current clinical practice pattern for lateral epicondylitis and identify factors
      that influence the introduction of evidence into clinical practice. METHODS: In
      this administrative claims analysis, the authors used 2009 to 2015 Truven
      MarketScan data to extract claims for corticosteroid injection, physical therapy,
      platelet-rich plasma injection, and surgery for lateral epicondylitis. The
      authors performed multivariable analysis using a generalized estimating equation
      model to identify the variables that potentially affect the odds of receiving a
      given treatment. RESULTS: Among 711,726 claims, the authors found that the odds
      of receiving a corticosteroid injection increased slightly after publication of
      contradictory evidence (OR, 1.7; 95 percent CI, 1.04 to 1.11 in 2015). Being male
      (OR, 1.21; 95 percent CI, 1.19 to 1.23), older (OR, 1.16; 95 percent CI, 1.13 to
      1.19), and having managed care insurance (OR, 1.15; 95 percent CI, 1.13 to 1.18)
      significantly contributed to increased odds of receiving corticosteroid
      injections. Patients seen at facilities in the South (OR, 1.33; 95 percent CI,
      1.30 to 1.36 compared with the Northeast) and by plastic/orthopedic surgeons (OR,
      2.48; 95 percent CI, 2.43 to 2.52) also had increased odds of receiving
      corticosteroid injection. CONCLUSIONS: Corticosteroid injection use did not
      decrease after publication of impactful articles, regardless of provider
      specialty or other patient-related factors. This finding emphasizes that there
      are various barriers for even high-level evidence to overcome the inertia of
      current practice.

PMID- 29351184
TI  - Cleft-Palate Repair: Does Hospital Case-Volume Impact Outcomes or Cost?
AB  - BACKGROUND: How hospital case-volume affects operative outcomes and cost
      continues to grow in importance. The purpose of this study was to examine the
      relationship of case volume with operative outcomes and cost in cleft palate
      repair. METHODS: Subjects undergoing cleft palate repair between 2004 and 2015
      were identified in the Pediatric Health Information System. Outcomes were
      compared between two groups: those undergoing treatment at a high-volume
      institution, and those undergoing treatment at a low-volume institution. Primary
      outcomes were as follows: any complication, prolonged length of stay, and
      increased total cost. RESULTS: Over 20,000 patients (n = 20,320) from 49
      institutions met inclusion criteria. On univariate analysis, those subjects who
      underwent treatment at a high-volume institution had a lower rate of overall
      complications (3.4 percent versus 5.1 percent; p < 0.001), and lower rates of
      prolonged length of stay (4.5 percent versus 5.8 percent; p < 0.001) and
      increased total cost (48.6 percent versus 50.9 percent; p = 0.002). In
      multivariate regression analyses, subjects treated in high-volume centers were
      less likely to experience any complication (OR, 0.678; p < 0.001) and were less
      likely to have an extended length of stay (OR, 0.82; p = 0.005). Subjects
      undergoing palate repair at a high-volume institution were no less likely to
      incur increased total cost (OR, 1.01; p = 0.805). CONCLUSION: In institutions
      performing a high volume of cleft palate repairs, subjects had significantly
      decreased odds of experiencing a complication or prolonged length of stay.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29351185
TI  - Brief Report: Lead Levels in Selected Electronic Cigarettes from Canada and the
      United States.
AB  - Few published studies have investigated the presence of lead in the e-liquid of
      electronic nicotine delivery systems (ENDS). Lead inhalation is associated with
      increased risk of stroke, heart disease, and other diseases. This study used a
      novel application of graphite furnace technology to compare the concentration of
      lead between e-liquids of different packaging and product designs using e-liquids
      that are or were commercially available in the United States and Canada. Eleven
      nicotine-free disposable ENDS devices and 12 bottled refill solutions that
      contained nicotine were purchased from retailers in Canada and the United States
      between 2015 and 2017. E-liquids extracted from the disposable products and
      individual containers were analyzed for lead content by graphite furnace using
      atomic absorption detection. The lead concentration of open-wick ENDS devices
      ranged from 25.2 ppb to 838.4 ppb, with a standard deviation of 187.4 ppb. None
      of the bottled e-liquids contained quantifiable levels of lead. This study found
      that quantifiable levels of lead are present in certain disposable e-cigarette
      devices, and there is evidence from this study that the design of ENDS devices
      may contribute to lead exposure. These findings suggest that lead testing should
      be incorporated into future chemical analyses of ENDS devices.

PMID- 29351186
TI  - Multiple Fano-Like MIM Plasmonic Structure Based on Triangular Resonator for
      Refractive Index Sensing.
AB  - In this paper, we present a Fano metal-insulator-metal (MIM) structure based on
      an isosceles triangular cavity resonator for refractive index sensing
      applications. Due to the specific feeding scheme and asymmetry introduced in the
      triangular cavity, the resonator exhibits four sharp Fano-like resonances. The
      behavior of the structure is analyzed in detail and its sensing capabilities
      demonstrated through the responses for various refractive indices. The results
      show that the sensor has very good sensitivity and maximal figure of merit (FOM)
      value of 3.2 * 105. In comparison to other similar sensors, the proposed one has
      comparable sensitivity and significantly higher FOM, which clearly demonstrates
      its high sensing potential.

PMID- 29351187
TI  - High Proportions of Multidrug-Resistant Acinetobacter spp. Isolates in a District
      in Western India: A Four-Year Antibiotic Susceptibility Study of Clinical
      Isolates.
AB  - The purpose of the study was to determine the proportions of multidrug-resistant
      (MDR) Acinetobacter spp. isolates from the district of Nashik in Western India
      during the period from 2011-2014. Antibacterial susceptibility testing of
      isolates from inpatients and outpatients was performed using Kirby-Bauer disc
      diffusion method to determine inhibitory zone diameters. Proportions of non
      susceptible isolates were calculated from the antibacterial susceptibility data.
      MDR was defined as an isolate being non-susceptible to at least one antibacterial
      agent in at least three antibacterial categories. The change in proportions of
      MDR isolates; extended-spectrum beta-lactamase (ESBL)-producing isolates; and non
      susceptible isolates to specific antibacterial categories over calendar time was
      investigated by logistic regression. The proportions of MDR and ESBL-producing
      isolates ranged from 89.4% to 95.9% and from 87.9% to 94.0%; respectively. The
      proportions of non-susceptible isolates to aminoglycosides; carbapenems;
      antipseudomonal penicillins/beta-lactamase inhibitors; cephalosporins; folate
      pathway inhibitors; or penicillins/beta-lactamase inhibitors exceeded 77.5%.
      Proportions of fluoroquinolone and tetracycline non-susceptible isolates ranged
      from 65.3% to 83.3% and from 71.3% to 75.9%; respectively. No changes in trends
      were observed over time; except for a decreasing trend in fluoroquinolone non
      susceptible isolates (OR = 0.75 (95% CI, 0.62-0.91)). Significantly higher
      proportions of non-susceptible; MDR and ESBL-producing isolates were found among
      isolates from the respiratory system compared to isolates from all other specimen
      types (p < 0.05). High proportions of MDR Acinetobacter spp. isolates were
      observed in the period from 2011-2014. Antimicrobial stewardship programmes are
      needed to prevent the emergence and spread of antibiotic resistance.

PMID- 29351189
TI  - The Role of Cadaverine Synthesis on Pneumococcal Capsule and Protein Expression.
AB  - Invasive infections caused by Streptococcus pneumoniae, a commensal in the
      nasopharynx, pose significant risk to human health. Limited serotype coverage by
      the available polysaccharide-based conjugate vaccines coupled with increasing
      incidence of antibiotic resistance complicates therapeutic strategies. Bacterial
      physiology and metabolism that allows pathogens to adapt to the host are a
      promising avenue for the discovery of novel therapeutics. Intracellular polyamine
      concentrations are tightly regulated by biosynthesis, transport and degradation.
      We previously reported that deletion of cadA, a gene that encodes for lysine
      decarboxylase, an enzyme that catalyzes cadaverine synthesis results in an
      attenuated phenotype. Here, we report the impact of cadA deletion on pneumococcal
      capsule and protein expression. Our data show that genes for polyamine
      biosynthesis and transport are downregulated in ?cadA. Immunoblot assays show
      reduced capsule in ?cadA. Reduced capsule synthesis could be due to reduced
      transcription and availability of precursors for synthesis. The capsule is the
      predominant virulence factor in pneumococci and is critical for evading
      opsonophagocytosis and its loss in ?cadA could explain the reported attenuation
      in vivo. Results from this study show that capsule synthesis in pneumococci is
      regulated by polyamine metabolism, which can be targeted for developing novel
      therapies.

PMID- 29351191
TI  - Anionic Water Cluster Polymers [(H2O)18(OH)2]n2n- Is Stabilized by Bis(2,2'
      bipyridine) Cupric Chloride [Cu(bipy)2Cl].
AB  - Anionic water clusters have long been studied to infer properties of the bulk
      hydrated electron. In particular, the question of whether the excess electron is
      on the surface of the cluster or in the interior of the clusters has been the
      subject of much speculation. The successes of solid-state physics are built on
      exploiting the regularity of atomic arrangements in crystal. Describing the
      crystalline order of solids is relatively straightforward. Here we report the
      crystal structure of an anionic water cluster polymer [(H2O)18(OH)2]n2n- moiety
      that is stabilized by bis(2,2'-bipyridine) cupric chloride [Cu(bipy)2Cl]- host.

PMID- 29351188
TI  - Proangiogenic Effect of Metformin in Endothelial Cells Is via Upregulation of
      VEGFR1/2 and Their Signaling under Hyperglycemia-Hypoxia.
AB  - Cardiovascular disease is the leading cause of morbidity/mortality worldwide.
      Metformin is the first therapy offering cardioprotection in type 2 diabetes and
      non-diabetic animals with unknown mechanism. We have shown that metformin
      improves angiogenesis via affecting expression of growth factors/angiogenic
      inhibitors in CD34+ cells under hyperglycemia-hypoxia. Now we studied the direct
      effect of physiological dose of metformin on human umbilical vein endothelial
      cells (HUVEC) under conditions mimicking hypoxia-hyperglycemia. HUVEC migration
      and apoptosis were studied after induction with euglycemia or hyperglycemia
      and/or CoCl2 induced hypoxia in the presence or absence of metformin. HUVEC mRNA
      was assayed by whole transcript microarrays. Genes were confirmed by qRT-PCR,
      proteins by western blot, ELISA or flow cytometry. Metformin promoted HUVEC
      migration and inhibited apoptosis via upregulation of vascular endothelial growth
      factor (VEGF) receptors (VEGFR1/R2), fatty acid binding protein 4 (FABP4),
      ERK/mitogen-activated protein kinase signaling, chemokine ligand 8, lymphocyte
      antigen 96, Rho kinase 1 (ROCK1), matrix metalloproteinase 16 (MMP16) and tissue
      factor inhibitor-2 under hyperglycemia-chemical hypoxia. Therefore, metformin's
      dual effect in hyperglycemia-chemical hypoxia is mediated by direct effect on
      VEGFR1/R2 leading to activation of cell migration through MMP16 and ROCK1
      upregulation, and inhibition of apoptosis by increase in phospho-ERK1/2 and
      FABP4, components of VEGF signaling cascades.

PMID- 29351192
TI  - Seed Endophyte Microbiome of Crotalaria pumila Unpeeled: Identification of Plant
      Beneficial Methylobacteria.
AB  - Metal contaminated soils are increasing worldwide. Metal-tolerant plants growing
      on metalliferous soils are fascinating genetic and microbial resources. Seeds can
      vertically transmit endophytic microorganisms that can assist next generations to
      cope with environmental stresses, through yet poorly understood mechanisms. The
      aims of this study were to identify the core seed endophyte microbiome of the
      pioneer metallophyte Crotalaria pumila throughout three generations, and to
      better understand the plant colonisation of the seed endophyte Methylobacterium
      sp. Cp3. Strain Cp3 was detected in C. pumila seeds across three successive
      generations and showed the most dominant community member. When inoculated in the
      soil at the time of flowering, strain Cp3 migrated from soil to seeds. Using
      confocal microscopy, Cp3-mCherry was demonstrated to colonise the root cortex
      cells and xylem vessels of the stem under metal stress. Moreover, strain Cp3
      showed genetic and in planta potential to promote seed germination and seedling
      development. We revealed, for the first time, that the seed microbiome of a
      pioneer plant growing in its natural environment, and the colonisation behaviour
      of an important plant growth promoting systemic seed endophyte. Future
      characterization of seed microbiota will lead to a better understanding of their
      functional contribution and the potential use for seed-fortification
      applications.

PMID- 29351193
TI  - Restricted Social Engagement among Adults Living with Chronic Conditions.
AB  - Background: Social engagement is key to health and quality of life. Little is
      known about social engagement patterns of middle-aged and older adults who live
      with one or more chronic illnesses. This study investigated social engagement
      restrictions among middle-aged and older adults with chronic conditions and
      factors associated with these restrictions. Methods: Cross-sectional
      representative data from the National Council on Aging Chronic Care Survey were
      examined for relationships between social engagement restrictions and chronic
      conditions, health status, support, quality of life implications, self-care
      barriers, caregiving, and demographics. Associations were tested using bivariate
      analyses and binary logistic regression. Results: Participants were 793 middle
      aged (age 44-64) and older adults (age 65+) with one or more chronic conditions.
      Factors associated with social engagement restrictions included having higher
      education, receiving care, having more physician visits and hospitalizations,
      being disabled, being unemployed, and having higher Emotional and Physical
      Problems Scale scores. Conclusions: Findings reveal the prevalence of social
      engagement restrictions among middle-aged and older adults with chronic
      conditions. Results highlight the importance of promoting research, assessments,
      and interventions to increase social engagement among this aging population.

PMID- 29351195
TI  - Seeing Context through Metaphor: Using Communications Research to Bring a Social
      Determinants Perspective to Public Thinking about Child Abuse and Neglect.
AB  - Human beings think in metaphor and reason through analogy. The metaphors through
      which we think influence how we understand and feel about social issues as well
      as the actions that we see as appropriate and important. Metaphors can be used to
      increase understanding of how issues work and increase the salience of a given
      issue, build support for programs and policies necessary to address the issue,
      and instigate demand for change and civic action. In this paper, we use a mixed
      methods research design, including brief qualitative interviews, experimental
      surveys, and focus groups, to test the ability of different metaphors to
      influence public understanding of the social determinants of child abuse and
      neglect in the UK. We find one metaphor in particular that improves people's
      understanding of the social causes of child maltreatment and increases support
      for structural solutions. This metaphor can be used to build support for
      preventative public health solutions.

PMID- 29351196
TI  - A Case Report of Disseminated Canine Histiocytic Sarcoma in Trinidad and Tobago.
AB  - Ocular histiocytic sarcomas (as a presenting part of disseminated histiocytic
      sarcoma) are not commonly diagnosed. A 10-year-old female intact Rottweiler
      presented to the School of Veterinary Medicine, Trinidad with buphthalmia and
      pain in the left eye. The cornea of the left eye appeared diffusely opaque with a
      conjunctival mucopurulent ocular discharge. A thorough ophthalmic assessment
      identified an intraocular proliferative tumor to which a unilateral enucleation
      was performed, however the animal died soon after. Post mortem examination and
      light microscopy revealed that the intraocular lesion with visceral macro
      metastases was in fact a histiocytic sarcoma. Further to this, immune-phenotyping
      was performed to confirm the diagnosis of disseminated histiocytic sarcoma. This
      is the first time such a tumor has been diagnosed in Trinidad and Tobago.

PMID- 29351194
TI  - Involvement of Bax and Bcl-2 in Induction of Apoptosis by Essential Oils of Three
      Lebanese Salvia Species in Human Prostate Cancer Cells.
AB  - Prostate cancer is one of the most common forms of cancer in men, and research to
      find more effective and less toxic drugs has become necessary. In the frame of
      our ongoing program on traditionally used Salvia species from the Mediterranean
      Area, here we report the biological activities of Salvia aurea, S. judaica and S.
      viscosa essential oils against human prostate cancer cells (DU-145). The cell
      viability was measured by 3(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium
      bromide (MTT) test and lactate dehydrogenase (LDH) release was used to quantify
      necrosis cell death. Genomic DNA, caspase-3 activity, expression of cleaved
      caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) proteins were
      analyzed in order to study the apoptotic process. The role of reactive oxygen
      species in cell death was also investigated. We found that the three essential
      oils, containing caryophyllene oxide as a main constituent, are capable of
      reducing the growth of human prostate cancer cells, activating an apoptotic
      process and increasing reactive oxygen species generation. These results suggest
      it could be profitable to further investigate the effects of these essential oils
      for their possible use as anticancer agents in prostate cancer, alone or in
      combination with chemotherapy agents.

PMID- 29351197
TI  - Announcing the 2018 Toxins Travel Awards for Post-Doctoral Fellows.
AB  - This year we enjoyed a large number of very highy meritorious applications for
      our annual Toxins Travel Awards.[...].

PMID- 29351198
TI  - Superoxide Dismutase Mimetic GC4419 Enhances the Oxidation of Pharmacological
      Ascorbate and Its Anticancer Effects in an H2O2-Dependent Manner.
AB  - Lung cancer, together with head and neck cancer, accounts for more than one
      fourth of cancer deaths worldwide. New, non-toxic therapeutic approaches are
      needed. High-dose IV vitamin C (aka, pharmacological ascorbate; P-AscH-)
      represents a promising adjuvant to radiochemotherapy that exerts its anti-cancer
      effects via metal-catalyzed oxidation to form H2O2. Mn(III)-porphyrins possessing
      superoxide dismutase (SOD) mimetic activity have been shown to increase the rate
      of oxidation of AscH-, enhancing the anti-tumor effects of AscH- in several
      cancer types. The current study demonstrates that the Mn(II)-containing
      pentaazamacrocyclic selective SOD mimetic GC4419 may serve as an AscH-/O2*-
      oxidoreductase as evidenced by the increased rate of oxygen consumption, steady
      state concentrations of ascorbate radical, and H2O2 production in complete cell
      culture media. GC4419, but not CuZnSOD, was shown to significantly enhance the
      toxicity of AscH- in H1299, SCC25, SQ20B, and Cal27 cancer cell lines. This
      enhanced cancer cell killing was dependent upon the catalytic activity of the SOD
      mimetic and the generation of H2O2, as determined using conditional
      overexpression of catalase in H1299T cells. GC4419 combined with AscH- was also
      capable of enhancing radiation-induced cancer cell killing. Currently, AscH- and
      GC4419 are each being tested separately in clinical trials in combination with
      radiation therapy. Data presented here support the hypothesis that the
      combination of GC4419 and AscH- may provide an effective means by which to
      further enhance radiation therapy responses.

PMID- 29351199
TI  - Biofilm-Forming Potential of Staphylococcus aureus Isolated from Clinical
      Mastitis Cases in New Zealand.
AB  - Biofilm formation is of growing concern in human and animal health. However, it
      is still unclear how biofilms are related to mastitis infections in dairy cattle.
      In this study, a comparison between two tests for biofilm formation and the
      association between biofilm and the presence of genes associated with biofilm
      formation were investigated for 92 Staphylococcus aureus isolates from clinical
      mastitis cases. Congo red agar (CRA) and microtitre test assay (MTA) in vitro
      phenotypic tests were used to evaluate biofilm formation. The presence of icaA,
      icaD, and bap genes associated with biofilm formation was confirmed using the
      polymerase chain reaction. Results show that most of the S. aureus isolates,
      though not possessing one of the biofilm-forming genes, were able to produce
      biofilms. MTA was more frequently positive in identifying biofilm-forming
      isolates than CRA.

PMID- 29351200
TI  - Comparing Nutrient Removal from Membrane Filtered and Unfiltered Domestic
      Wastewater Using Chlorella vulgaris.
AB  - The nutrient removal efficiency of Chlorella vulgaris cultivated in domestic
      wastewater was investigated, along with the potential to use membrane filtration
      as a pre-treatment tool during the wastewater treatment process. Chlorella
      vulgaris was batch cultivated for 12 days in a bubble column system with two
      different wastewater treatments. Maximum uptake of 94.18% ammonium (NH4-N) and
      97.69% ortho-phosphate (PO4-P) occurred in 0.2 MUm membrane filtered primary
      wastewater. Membrane filtration enhanced the nutrient uptake performance of C.
      vulgaris by removing bacteria, protozoa, colloidal particles and suspended
      solids, thereby improving light availability for photosynthesis. The results of
      this study suggest that growing C. vulgaris in nutrient rich membrane filtered
      wastewater provides an option for domestic wastewater treatment to improve the
      quality of the final effluent.

PMID- 29351201
TI  - In Vivo Characterisation of Five Strains of Bovine Viral Diarrhoea Virus 1
      (Subgenotype 1c).
AB  - Bovine viral diarrhoea virus 1 (BVDV-1) is strongly associated with several
      important diseases of cattle, such as bovine respiratory disease, diarrhoea and
      haemoragic lesions. To date many subgenotypes have been reported for BVDV-1,
      currently ranging from subgenotype 1a to subgenotype 1u. While BVDV-1 has a world
      wide distribution, the subgenotypes have a more restricted geographical
      distribution. As an example, BVDV-1 subgenotypes 1a and 1b are frequently
      detected in North America and Europe, while the subgenotype 1c is rarely
      detected. In contrast, BVDV-1 subgenotype 1c is by far the most commonly reported
      in Australia. Despite this, uneven distribution of the biological importance of
      the subgenotypes remains unclear. The aim of this study was to characterise the
      in vivo properties of five strains of BVDV-1 subgenotype 1c in cattle infection
      studies. No overt respiratory signs were reported in any of the infected cattle
      regardless of strain. Consistent with other subgenotypes, transient pyrexia and
      leukopenia were commonly identified, while thrombocytopenia was not. The quantity
      of virus detected in the nasal secretions of transiently infected animals
      suggested the likelihood of horizontal transmission was very low. Further studies
      are required to fully understand the variability and importance of the BVDV-1
      subgenotype 1c.

PMID- 29351203
TI  - TTX-Bearing Planocerid Flatworm (Platyhelminthes: Acotylea) in the Ryukyu
      Islands, Japan.
AB  - Polyclad flatworms comprise a highly diverse and cosmopolitan group of marine
      turbellarians. Although some species of the genera Planocera and Stylochoplana
      are known to be tetrodotoxin (TTX)-bearing, there are few new reports. In this
      study, planocerid-like flatworm specimens were found in the sea bottom off the
      waters around the Ryukyu Islands, Japan. The bodies were translucent with brown
      reticulate mottle, contained two conical tentacles with eye spots clustered at
      the base, and had a slightly frilled-body margin. Each specimen was subjected to
      TTX extraction followed by liquid chromatography with tandem mass spectrometry
      analysis. Mass chromatograms were found to be identical to those of the TTX
      standards. The TTX amounts in the two flatworm specimens were calculated to be
      468 and 3634 MUg. Their external morphology was found to be identical to that of
      Planocera heda. Phylogenetic analysis based on the sequences of the 28S rRNA gene
      and cytochrome-c oxidase subunit I gene also showed that both specimens clustered
      with the flatworms of the genus Planocera (Planocera multitentaculata and
      Planocera reticulata). This fact suggests that there might be other Planocera
      species that also possess highly concentrated TTX, contributing to the
      toxification of TTX-bearing organisms, including fish.

PMID- 29351202
TI  - Antimicrobial Peptides: Diversity, Mechanism of Action and Strategies to Improve
      the Activity and Biocompatibility In Vivo.
AB  - Antibiotic resistance is projected as one of the greatest threats to human health
      in the future and hence alternatives are being explored to combat resistance.
      Antimicrobial peptides (AMPs) have shown great promise, because use of AMPs leads
      bacteria to develop no or low resistance. In this review, we discuss the
      diversity, history and the various mechanisms of action of AMPs. Although many
      AMPs have reached clinical trials, to date not many have been approved by the US
      Food and Drug Administration (FDA) due to issues with toxicity, protease cleavage
      and short half-life. Some of the recent strategies developed to improve the
      activity and biocompatibility of AMPs, such as chemical modifications and the use
      of delivery systems, are also reviewed in this article.

PMID- 29351205
TI  - Influence of Grapevine Cultivar on the Second Generations of Lobesia botrana and
      Eupoecilia ambiguella.
AB  - Grapevine cultivar can affect susceptibility to Lobesia botrana and Eupoecilia
      ambiguella with important implications on control strategies. A four-year study
      was carried out in north-eastern Italy on 10 cultivars (Cabernet Sauvignon,
      Carmenere, Chardonnay, Merlot, Refosco dal Peduncolo Rosso, Rhine Riesling,
      Sauvignon Blanc, Terrano, Tocai Friulano and Verduzzo Friulano) grown in the same
      vineyard to assess whether the cultivar affects second-generation population
      levels of the two vine moths and L. botrana larval age composition. The influence
      of bunch traits measured at the peak of egg hatching on demographic parameters
      was also evaluated. Over the four years, L. botrana significantly prevailed over
      E. ambiguella in nine cultivars. Chardonnay and Tocai Friulano were the most
      infested cultivars and Merlot was the least infested. At the sampling date, the
      age composition of L. botrana varied with cultivar, with the larvae being
      significantly older on Chardonnay and younger on Carmenere, Merlot and Verduzzo
      Friulano. Older larval age was significantly associated with higher bunch
      compactness. Larval infestation was not significantly influenced by either bunch
      compactness or berry volume, which suggested a more important role for contact
      and volatile substances mostly originating from the berries. These results allow
      for the improvement of Integrated Pest Management strategy against vine moths.

PMID- 29351206
TI  - Antibody Biomimetic Material Made of Pyrrole for CA 15-3 and Its Application as
      Sensing Material in Ion-Selective Electrodes for Potentiometric Detection.
AB  - This work reports a very simple approach for creating a synthetic antibody
      against any protein of interest and its application in potentiometric
      transduction. The selected protein was Breast Cancer Antigen (CA 15-3), which is
      implicated in breast cancer disease and used to follow-up breast cancer patients
      during treatment. The new material with antibody-like properties was obtained by
      molecular-imprinting technology, prepared by electropolymerizing pyrrol (Py, 5.0
      * 10-3 mol/L) around Breast Cancer Antigen (CA 15-3) (100 U/mL) on a fluorine
      doped tin oxide (FTO) conductive glass support. Cyclic voltammetry was employed
      for this purpose. All solutions were prepared in 4-(2-Hydroxyethyl)-1
      piperazineethanesulfonic acid (HEPES) buffer, of pH 6.5. The biomarker was
      removed from the imprinted sites by chemical action of ethanol. The biomimetic
      material was then included in poly vinyl chloride (PVC) plasticized membranes to
      act as potentiometric ionophore, having or not a lipophilic ionic additive added.
      The corresponding selective electrodes were evaluated by calibration curves (in
      buffer and in synthetic serum) and by selectivity testing. The best analytical
      performance was obtained by selective electrodes including the plastic antibody
      and no lipophilic additive. The average limits of detection were 1.07 U/mL of CA
      15-3, with a linear response from 1.44 to 13.2 U/mL and a cationic slope of 44.5
      mV/decade. Overall, the lipophilic additives yielded no advantage to the overall
      potentiometric performance. The application of the MIP-based electrodes to the
      analysis of spiked synthetic serum showed precise and accurate results.

PMID- 29351207
TI  - Diabetic Retinopathy Screening: A Systematic Review on Patients' Non-Attendance.
AB  - Diabetic Retinopathy is a microvascular complication of diabetes, that can go
      undetected and unnoticed until irreversible damage and even blindness has
      occurred. Effective screening for diabetic retinopathy has been proven to reduce
      the risk of sight loss. The National Health Service (NHS) which provides
      healthcare for all UK citizens, implemented systematic retinal screening for
      diabetic retinopathy in England in 2003, with the aim of identifying and treating
      all patients with sight threatening retinopathy. Crucial to this is patients
      partaking in the programme. Therefore, increasing screening uptake has been a
      major focus of the programme. This review explores the views of people living
      with diabetes who do not attend retinal screening, their characteristics,
      concerns, experiences of retinal screening and their understanding of the risks
      of diabetic retinopathy. All studies that satisfied the study inclusion criteria
      on 'patients' non-attendance at retinal screening', between 2003 to 2017 were
      included after extensive database search. A total of 16 studies were included in
      the review. Findings showed that socio-economic deprivation was a major risk
      factor for non-attendance, about 11.5-13.4% of the screened population had sight
      threatening retinopathy (STDR), repeated nonattendance was linked to sight
      threatening diabetic retinopathy, and that certain factors, could be barriers or
      incentives for screening uptake. Some of those factors are modifiable whilst
      others are not.

PMID- 29351204
TI  - mTOR Cross-Talk in Cancer and Potential for Combination Therapy.
AB  - The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in
      sensing and integrating a variety of exogenous cues to regulate cellular growth
      and metabolism, in both physiological and pathological conditions. mTOR functions
      through two functionally and structurally distinct multi-component complexes,
      mTORC1 and mTORC2, which interact with each other and with several elements of
      other signaling pathways. In the past few years, many new insights into mTOR
      function and regulation have been gained and extensive genetic and
      pharmacological studies in mice have enhanced our understanding of how mTOR
      dysfunction contributes to several diseases, including cancer. Single-agent mTOR
      targeting, mostly using rapalogs, has so far met limited clinical success;
      however, due to the extensive cross-talk between mTOR and other pathways,
      combined approaches are the most promising avenues to improve clinical efficacy
      of available therapeutics and overcome drug resistance. This review provides a
      brief and up-to-date narrative on the regulation of mTOR function, the relative
      contributions of mTORC1 and mTORC2 complexes to cancer development and
      progression, and prospects for mTOR inhibition as a therapeutic strategy.

PMID- 29351208
TI  - Preservation Method and Phosphate Buffered Saline Washing Affect the Acute
      Myeloid Leukemia Proteome.
AB  - Acute myeloid leukemia (AML) primary cells can be isolated from peripheral blood,
      suspended with media containing bovine serum and cryoprotectant, and stored in
      liquid nitrogen before being processed for proteomic analysis by mass
      spectrometry (MS). The presence of bovine serum and human blood proteins in AML
      samples can hamper the identifications of proteins, and thereby reduce the
      proteome coverage of the study. Herein, we have established the effect of
      phosphate buffered saline (PBS) washing on AML patient samples stored in media.
      Although PBS washes effectively removed serum and blood contaminants, the saline
      wash resulted in cell burst and remarkable protein material loss. We also
      compared different methods to preserve the AML proteome from THP-1 and Molm-13
      cell lines before MS analysis: (1) stored in media containing bovine serum and
      dimethyl sulfoxide (DMSO); (2) stored as dried cell pellets; and (3) stored as
      cell lysates in 4% sodium dodecyl sulfate (SDS). MS analysis of differently
      preserved AML cell samples shows that preservation with DMSO produce a high
      number of fragile cells that will burst during freezing and thawing. Our studies
      encourage the use of alternative preservation methods for future MS analysis of
      the AML proteome.

PMID- 29351210
TI  - A High Sensitivity Electric Field Microsensor Based on Torsional Resonance.
AB  - This paper proposes a high sensitivity electric field microsensor (EFM) based on
      torsional resonance. The proposed microsensor adopts torsional shutter, which is
      composed of shielding electrodes and torsional beams. The movable shielding
      electrodes and the fixed sensing electrodes are fabricated on the same plane and
      interdigitally arranged. Push-pull electrostatic actuation method is employed to
      excite the torsional shutter. Simulation results proved that the torsional
      shutter has higher efficiency of charge induction. The optimization of structure
      parameters was conducted to improve its efficiency of charge induction further. A
      micromachining fabrication process was developed to fabricate the EFM.
      Experiments were conducted to characterize the EFM. A good linearity of 0.15% was
      achieved within an electrostatic field range of 0-50 kV/m, and the uncertainty
      was below 0.38% in the three roundtrip measurements. A high sensitivity of 4.82
      mV/(kV/m) was achieved with the trans-resistance of 100 MOmega, which is improved
      by at least one order of magnitude compared with previously reported EFMs. The
      efficiency of charge induction for this microsensor reached 48.19 pA/(kV/m).

PMID- 29351211
TI  - Wide-Field Fluorescence Microscopy of Real-Time Bioconjugation Sensing.
AB  - We apply wide-field fluorescence microscopy to measure real-time attachment of
      photosynthetic proteins to plasmonically active silver nanowires. The observation
      of this effect is enabled, on the one hand, by sensitive detection of
      fluorescence and, on the other hand, by plasmonic enhancement of protein
      fluorescence. We examined two sample configurations with substrates being a bare
      glass coverslip and a coverslip functionalized with a monolayer of streptavidin.
      The different preparation of the substrate changes the observed behavior as far
      as attachment of the protein is concerned as well as its subsequent
      photobleaching. For the latter substrate the conjugation process is measurably
      slower. The described method can be universally applied in studying protein
      nanostructure interactions for real-time fluorescence-based sensing.

PMID- 29351209
TI  - The Prognostic Significance of Histone Demethylase UTX in Esophageal Squamous
      Cell Carcinoma.
AB  - The dysregulation of the ubiquitously transcribed TPR gene on the X chromosome
      (UTX) has been reported to be involved in the oncogenesis of several types of
      cancers. However, the expression and significance of UTX in esophageal squamous
      cell carcinoma (ESCC) remains largely undetermined. Immunohistochemistry was
      performed in 106 ESCC patients, and correlated with clinicopathological features
      and survival. The functional role of UTX in ESCC cells was determined by UTX
      mediated siRNA. Univariate analyses showed that high UTX expression was
      associated with superior overall survival (OS, p = 0.011) and disease-free
      survival (DFS, p = 0.01). UTX overexpression was an independent prognosticator in
      multivariate analysis for OS (p = 0.013, hazard ratio = 1.996) and DFS (p =
      0.009, hazard ratio = 1.972). The 5-year OS rates were 39% and 61% in patients
      with low expression and high expression of UTX, respectively. Inhibition of
      endogenous UTX in ESCC cells increased cell viability and BrdU incorporation, and
      decreased the expression of epithelial marker E-cadherin. Immunohistochemically,
      UTX expression was also positively correlated with E-cadherin expression. High
      UTX expression is independently associated with a better prognosis in patients
      with ESCC and downregulation of UTX increases ESCC cell growth and decreases E
      cadherin expression. Our results suggest that UTX may be a novel therapeutic
      target for patients with ESCC.

PMID- 29351212
TI  - Changes in the Expression of AQP4 and AQP9 in the Hippocampus Following Eclampsia
      Like Seizure.
AB  - Eclampsia is a hypertensive disorder of pregnancy that is defined by the new
      onset of grand mal seizures on the basis of pre-eclampsia. Until now, the
      mechanisms underlying eclampsia were poorly understood. Brain edema is considered
      a leading cause of eclamptic seizures; aquaporins (AQP4 and AQP9), the glial
      water channel proteins mainly expressed in the nervous system, play an important
      role in brain edema. We studied AQP4 and AQP9 expression in the hippocampus of
      pre-eclamptic and eclamptic rats in order to explore the molecular mechanisms
      involved in brain edema. Using our previous animal models, we found several
      neuronal deaths in the hippocampal CA1 and CA3 regions after pre-eclampsia and
      that eclampsia induced more neuronal deaths in both areas by Nissl staining. In
      the current study, RT-PCR and Western blotting data showed significant
      upregulation of AQP4 and AQP9 mRNA and protein levels after eclamptic seizures in
      comparison to pre-eclampsia and at the same time AQP4 and AQP9 immunoreactivity
      also increased after eclampsia. These findings showed that eclamptic seizures
      induced cell death and that upregulation of AQP4 and AQP9 may play an important
      role in this pathophysiological process.

PMID- 29351215
TI  - Multi-Sensor Data Integration Using Deep Learning for Characterization of Defects
      in Steel Elements.
AB  - Nowadays, there is a strong demand for inspection systems integrating both high
      sensitivity under various testing conditions and advanced processing allowing
      automatic identification of the examined object state and detection of threats.
      This paper presents the possibility of utilization of a magnetic multi-sensor
      matrix transducer for characterization of defected areas in steel elements and a
      deep learning based algorithm for integration of data and final identification of
      the object state. The transducer allows sensing of a magnetic vector in a single
      location in different directions. Thus, it enables detecting and characterizing
      any material changes that affect magnetic properties regardless of their
      orientation in reference to the scanning direction. To assess the general
      application capability of the system, steel elements with rectangular-shaped
      artificial defects were used. First, a database was constructed considering
      numerical and measurements results. A finite element method was used to run a
      simulation process and provide transducer signal patterns for different defect
      arrangements. Next, the algorithm integrating responses of the transducer
      collected in a single position was applied, and a convolutional neural network
      was used for implementation of the material state evaluation model. Then,
      validation of the obtained model was carried out. In this paper, the procedure
      for updating the evaluated local state, referring to the neighboring area
      results, is presented. Finally, the results and future perspective are discussed.

PMID- 29351213
TI  - Cyclin B3 Deficiency Impairs Germline Stem Cell Maintenance and Its
      Overexpression Delays Cystoblast Differentiation in Drosophila Ovary.
AB  - It is well known that cyclinB3 (cycB3) plays a key role in the control of cell
      cycle progression. However, whether cycB3 is involved in stem cell fate
      determination remains unknown. The Drosophila ovary provides an exclusive model
      for studying the intrinsic and extrinsic factors that modulate the fate of
      germline stem cells (GSCs). Here, using this model, we show that DrosophilacycB3
      plays a new role in controlling the fate of germline stem cells (GSC). Results
      from cycB3 genetic analyses demonstrate that cycB3 is intrinsically required for
      GSC maintenance. Results from green fluorescent protein (GFP)-transgene reporter
      assays show that cycB3 is not involved in Dad-mediated regulation of Bmp
      signaling, or required for dpp-induced bam transcriptional silencing. Double
      mutants of bam and cycB3 phenocopied bam single mutants, suggesting that cycB3
      functions in a bam-dependent manner in GSCs. Deficiency of cycB3 fails to cause
      apoptosis in GSCs or influence cystoblast (CB) differentiation into oocytes.
      Furthermore, overexpression of cycB3 dramatically increases the CB number in
      Drosophila ovaries, suggesting that an excess of cycB3 function delays CB
      differentiation. Given that the cycB3 gene is evolutionarily conserved, from
      insects to humans, cycB3 may also be involved in controlling the fate of GSCs in
      humans.

PMID- 29351214
TI  - Synthesis and Evaluation of the Antioxidant Activity of Lipophilic Phenethyl
      Trifluoroacetate Esters by In Vitro ABTS, DPPH and in Cell-Culture DCF Assays.
AB  - Polyphenols are natural compounds showing a variety of health-promoting effects.
      Unfortunately, due to low lipid solubility, their applications in the
      pharmaceutical, food, and cosmetic industries are limited. With the aim of
      obtaining novel lipophilic derivatives, the present study reports the synthesis
      of a series of phenethyl trifluoroacetate esters containing up to two hydroxyl
      groups in the aromatic ring. Experimental logP values confirmed a greater
      lipophilicity of the novel compounds compared to the parent compounds. The
      radical scavenging capacity of all phenethyl trifluoroacetate esters was
      evaluated by in vitro assays (ABTS, DPPH) and in cultured cells (L6 myoblasts and
      THP-1 leukemic monocytes) using 2',7'-dichlorodihydrofluorescein diacetate. These
      data revealed that the esters showed a good antioxidant effect that was strictly
      dependent on the grade of hydroxylation of the phenyl ring. The lack of toxicity,
      evaluated by the MTT assay and proliferation curves, makes these
      trifluoroacetates attractive derivatives for pharmaceutical, food, and cosmetic
      applications.

PMID- 29351216
TI  - In Silico and In Vitro Study of the Bromelain-Phytochemical Complex Inhibition of
      Phospholipase A2 (Pla2).
AB  - Phospholipase A2 (Pla2) is an enzyme that induces inflammation, making Pla2
      activity an effective approach to reduce inflammation. Therefore, investigating
      natural compounds for this Pla2 inhibitory activity has important therapeutic
      potential. The objective of this study was to investigate the potential in
      bromelain-phytochemical complex inhibitors via a combination of in silico and in
      vitro methods. Bromelain-amenthoflavone displays antagonistic effects on Pla2.
      Bromelian-asiaticoside and bromelain-diosgenin displayed synergistic effects at
      high concentrations of the combined compounds, with inhibition percentages of
      more than 70% and 90%, respectively, and antagonistic effects at low
      concentrations. The synergistic effect of the bromelain-asiaticoside and
      bromelain-diosgenin combinations represents a new application in treating
      inflammation. These findings not only provide significant quantitative data, but
      also provide an insight on valuable implications for the combined use of
      bromelain with asiaticoside and diosgenin in treating inflammation, and may help
      researchers develop more natural bioactive compounds in daily foods as anti
      inflammatory agent.

PMID- 29351217
TI  - Nitrogen-Containing Functional Groups-Facilitated Acetone Adsorption by ZIF-8
      Derived Porous Carbon.
AB  - Nitrogen-doped porous carbon (ZC) is prepared by modification with ammonia for
      increasing the specific surface area and surface polarity after carbonization of
      zeolite imidazole framework-8 (ZIF-8). The structure and properties of these ZCs
      were characterized by Transmission electron microscopy, X-ray diffraction, N2
      sorption, X-ray photoelectron spectroscopy and Fourier transform infrared
      spectroscopy. Through static adsorption tests of these carbons, the sample
      obtained at 600  degrees C was selected as an excellent adsorbent, which
      exhibited an excellent acetone capacity of 417.2 mg g-1 (25  degrees C) with a
      very large surface area and high-level nitrogen doping (13.55%). The
      microporosity, surface area and N-containing groups of the materials, pyrrolic-N,
      pyridinic-N, and oxidized-N groups in particular, were found to be the
      determining factors for acetone adsorption by means of molecular simulation with
      density functional theory. These findings indicate that N-doped microporous
      carbon materials are potential promising adsorbents for acetone.

PMID- 29351219
TI  - Investigating Binge Eating Using Ecological Momentary Assessment: The Importance
      of an Appropriate Sampling Frequency.
AB  - With great interest, we read the recently published review on emotion regulation
      in binge eating disorder (BED) by Dingemans et al. [1].[...].

PMID- 29351218
TI  - Transparent Fingerprint Sensor System for Large Flat Panel Display.
AB  - In this paper, we introduce a transparent fingerprint sensing system using a thin
      film transistor (TFT) sensor panel, based on a self-capacitive sensing scheme. An
      armorphousindium gallium zinc oxide (a-IGZO) TFT sensor array and associated
      custom Read-Out IC (ROIC) are implemented for the system. The sensor panel has a
      200 * 200 pixel array and each pixel size is as small as 50 MUm * 50 MUm. The
      ROIC uses only eight analog front-end (AFE) amplifier stages along with a
      successive approximation analog-to-digital converter (SAR ADC). To get the
      fingerprint image data from the sensor array, the ROIC senses a capacitance,
      which is formed by a cover glass material between a human finger and an electrode
      of each pixel of the sensor array. Three methods are reviewed for estimating the
      self-capacitance. The measurement result demonstrates that the transparent
      fingerprint sensor system has an ability to differentiate a human finger's ridges
      and valleys through the fingerprint sensor array.

PMID- 29351220
TI  - Assessment of Validity and Reproducibility of the Zinc-Specific Dietary Intake
      Questionnaire Conducted for Young Polish Female Respondents.
AB  - One of the brief methods enabling the assessment of the zinc intake and
      identification of individuals characterized by insufficient zinc intake, is zinc
      specific food frequency questionnaire. The aim of the study was to assess the
      validity and reproducibility of the elaborated zinc-specific food frequency
      questionnaire ZINC-FFQ (Zinc INtake Calculation-Food Frequency Questionnaire) in
      a group of young Polish female respondents. The validity was assessed in
      comparison with 3-day dietary records, while reproducibility was assessed for the
      ZINC-FFQ filled in twice (FFQ1 and FFQ2-six weeks apart). Bland-Altman indexes in
      the assessment of validity were 5.5% (FFQ1) and 6.7% (FFQ2), while in assessment
      of reproducibility it was 3.3%. In the assessment of reproducibility, 83% of
      respondents were classified into the same category of zinc intake adequacy and
      72% of respondents were classified into the same tertile, that contributed to
      weighted kappa statistic of 0.65 (substantial agreement). It may be concluded,
      that ZINC-FFQ is characterized by a validity on a satisfactory and
      reproducibility on a very good level, in a group of young Polish female
      respondents, and may be applied to indicate individuals characterized by the risk
      of insufficient intake.

PMID- 29351221
TI  - Mechanical Structural Design of a MEMS-Based Piezoresistive Accelerometer for
      Head Injuries Monitoring: A Computational Analysis by Increments of the Sensor
      Mass Moment of Inertia.
AB  - This work focuses on the proof-mass mechanical structural design improvement of a
      tri-axial piezoresistive accelerometer specifically designed for head injuries
      monitoring where medium-G impacts are common; for example, in sports such as
      racing cars or American Football. The device requires the highest sensitivity
      achievable with a single proof-mass approach, and a very low error (<1%) as the
      accuracy for these types of applications is paramount. The optimization method
      differs from previous work as it is based on the progressive increment of the
      sensor proof-mass mass moment of inertia (MMI) in all three axes. Three different
      designs are presented in this study, where at each step of design evolution, the
      MMI of the sensor proof-mass gradually increases in all axes. The work
      numerically demonstrates that an increment of MMI determines an increment of
      device sensitivity with a simultaneous reduction of cross-axis sensitivity in the
      particular axis under study. This is due to the linkage between the external
      applied stress and the distribution of mass (of the proof-mass), and therefore of
      its mass moment of inertia. Progressively concentrating the mass on the axes
      where the piezoresistors are located (i.e., x- and y-axis) by increasing the MMI
      in the x- and y-axis, will undoubtedly increase the longitudinal stresses applied
      in that areas for a given external acceleration, therefore increasing the
      piezoresistors fractional resistance change and eventually positively affecting
      the sensor sensitivity. The final device shows a sensitivity increase of about
      80% in the z-axis and a reduction of cross-axis sensitivity of 18% respect to
      state-of-art sensors available in the literature from a previous work of the
      authors. Sensor design, modelling, and optimization are presented, concluding the
      work with results, discussion, and conclusion.

PMID- 29351222
TI  - Association between Work Related Stress and Health Related Quality of Life: The
      Impact of Socio-Demographic Variables. A Cross Sectional Study in a Region of
      Central Italy.
AB  - The aim of this work is investigate relationship between health-related quality
      of life and work-related stress and the impact of gender, education level, and
      age on this relationship. A cross-sectional study was conducted among workers of
      various setting in Rome and Frosinone. Work-related stress was measured with a
      demand-control questionnaire and health-related functioning by SF (short form)-12
      health survey. There were 611 participants. Men reported high mental composite
      summary (MCS) and physical composite summary (PCS). In multivariate analysis age,
      gender (p < 0.001) and job demand (0.045) predicted low PCS. Low MCS predicted
      poor PCS. Job demand and educational level resulted negatively associated with
      MCS. In an analysis stratified for age, gender, and educational level, gender and
      age resulted effect modifier for MCS, gender and education level for PCS. In
      women increase of decision latitude predict (p = 0.001) an increase in MCS; a low
      job demand predict high MCS in male (p <= 0.001). In younger workers, a lower
      level of job demand predicted high MCS (<0.001). For PCS, gender and education
      level resulted effect modifier. In women, high decision latitude predicted higher
      PCS (p = 0.001) and lower level of job demand results in higher PCS (p <= 0.001).
      Higher educational level resulted predictor of low PCS. Management of risk about
      work-related stress should consider socio-demographic factors.

PMID- 29351223
TI  - A Novel Walking Detection and Step Counting Algorithm Using Unconstrained
      Smartphones.
AB  - Recently, with the development of artificial intelligence technologies and the
      popularity of mobile devices, walking detection and step counting have gained
      much attention since they play an important role in the fields of equipment
      positioning, saving energy, behavior recognition, etc. In this paper, a novel
      algorithm is proposed to simultaneously detect walking motion and count steps
      through unconstrained smartphones in the sense that the smartphone placement is
      not only arbitrary but also alterable. On account of the periodicity of the
      walking motion and sensitivity of gyroscopes, the proposed algorithm extracts the
      frequency domain features from three-dimensional (3D) angular velocities of a
      smartphone through FFT (fast Fourier transform) and identifies whether its holder
      is walking or not irrespective of its placement. Furthermore, the corresponding
      step frequency is recursively updated to evaluate the step count in real time.
      Extensive experiments are conducted by involving eight subjects and different
      walking scenarios in a realistic environment. It is shown that the proposed
      method achieves the precision of 93.76 % and recall of 93.65 % for walking
      detection, and its overall performance is significantly better than other well
      known methods. Moreover, the accuracy of step counting by the proposed method is
      95.74 % , and is better than both of the several well-known counterparts and
      commercial products.

PMID- 29351224
TI  - N-Dimensional LLL Reduction Algorithm with Pivoted Reflection.
AB  - The Lenstra-Lenstra-Lovasz (LLL) lattice reduction algorithm and many of its
      variants have been widely used by cryptography, multiple-input-multiple-output
      (MIMO) communication systems and carrier phase positioning in global navigation
      satellite system (GNSS) to solve the integer least squares (ILS) problem. In this
      paper, we propose an n-dimensional LLL reduction algorithm (n-LLL), expanding the
      Lovasz condition in LLL algorithm to n-dimensional space in order to obtain a
      further reduced basis. We also introduce pivoted Householder reflection into the
      algorithm to optimize the reduction time. For an m-order positive definite
      matrix, analysis shows that the n-LLL reduction algorithm will converge within
      finite steps and always produce better results than the original LLL reduction
      algorithm with n > 2. The simulations clearly prove that n-LLL is better than the
      original LLL in reducing the condition number of an ill-conditioned input matrix
      with 39% improvement on average for typical cases, which can significantly reduce
      the searching space for solving ILS problem. The simulation results also show
      that the pivoted reflection has significantly declined the number of swaps in the
      algorithm by 57%, making n-LLL a more practical reduction algorithm.

PMID- 29351225
TI  - A Composite Photocatalyst Based on Hydrothermally-Synthesized Cu2ZnSnS4 Powders.
AB  - A novel composite photocatalyst based on Cu2ZnSnS4 (CZTS) powders was synthesized
      and investigated for use as a photocatalyst. CZTS powders were first made using a
      conventional hydrothermal method and were then used to grow silver nanoparticles
      hybridized onto the CZTS under various conditions through a microwave-assisted
      hydrothermal process. After the obtained samples were subsequently mixed with 1T
      2H MoS2, the three synthesized component samples were characterized using X-ray
      diffractometry (XRD), scanning electron microscopy, transmission electron
      microscopy (FE-SEM, FE-TEM), UV-visible spectroscopy (UV-Vis), Brunauer-Emmet
      Teller (BET), photoluminescence spectroscopy (PL), and X-ray photoelectron
      spectroscopy (XPS). The resulting samples were also used as photocatalysts for
      the degradation of methylene blue (MB) under a 300 W halogen lamp simulating
      sunlight with ~5% UV light. The photodegradation ability was greatly enhanced by
      the addition of Ag and 1T-2H MoS2. Excellent photodegradation of MB was obtained
      under visible light. The effects of material characteristics on the
      photodegradation were investigated and discussed.

PMID- 29351228
TI  - Erratum: Lydia Visser et al. Characterization of the Microenvironment of Nodular
      Lymphocyte Predominant Hodgkin Lymphoma, Int. J. Mol. Sci. 2016, 17, 2127.
AB  - The authors regret to have made a mistake in publishing this paper [1] with an
      incorrect author list [...].

PMID- 29351227
TI  - Differential Association of Cx37 and Cx40 Genetic Variants in Atrial Fibrillation
      with and without Underlying Structural Heart Disease.
AB  - Atrial fibrillation (AF) appears in the presence or absence of structural heart
      disease. The majority of foci causing AF are located near the ostia of pulmonary
      veins (PVs), where cardiomyocytes and vascular smooth muscle cells interdigitate.
      Connexins (Cx) form gap junction channels and participate in action potential
      propagation. Genetic variants in genes encoding Cx40 and Cx37 affect their
      expression or function and may contribute to PV arrhythmogenicity. DNA was
      obtained from 196 patients with drug-resistant, symptomatic AF with and without
      structural heart disease, who were referred for percutaneous catheter ablation.
      Eighty-nine controls were matched for age, gender, hypertension, and BMI.
      Genotyping of the Cx40 -44G > A, Cx40 +71A > G, Cx40 -26A > G, and Cx37 1019C > T
      polymorphisms was performed. The promoter A Cx40 polymorphisms (-44G > A and +71A
      > G) showed no association with non-structural or structural AF. Distribution of
      the Cx40 promoter B polymorphism (-26A > G) was different in structural AF when
      compared to controls (p = 0.03). There was no significant difference with non
      structural AF (p = 0.50). The distribution of the Cx37 1019C > T polymorphism was
      different in non-structural AF (p = 0.03) but not in structural AF (p = 0.08)
      when compared to controls. Our study describes for the first time an association
      of drug-resistant non-structural heart disease AF with the Cx37 1019C > T gene
      polymorphism. We also confirmed the association of the Cx40 - 26G > A
      polymorphism in patients with AF and structural disease.

PMID- 29351229
TI  - Joint Bearing and Range Estimation of Multiple Objects from Time-Frequency
      Analysis.
AB  - Direction-of-arrival (DOA) and range estimation is an important issue of sonar
      signal processing. In this paper, a novel approach using Hilbert-Huang transform
      (HHT) is proposed for joint bearing and range estimation of multiple targets
      based on a uniform linear array (ULA) of hydrophones. The structure of this ULA
      based on micro-electro-mechanical systems (MEMS) technology, and thus has
      attractive features of small size, high sensitivity and low cost, and is suitable
      for Autonomous Underwater Vehicle (AUV) operations. This proposed target
      localization method has the following advantages: only a single snapshot of data
      is needed and real-time processing is feasible. The proposed algorithm transforms
      a very complicated nonlinear estimation problem to a simple nearly linear one via
      time-frequency distribution (TFD) theory and is verified with HHT. Theoretical
      discussions of resolution issue are also provided to facilitate the design of a
      MEMS sensor with high sensitivity. Simulation results are shown to verify the
      effectiveness of the proposed method.

PMID- 29351226
TI  - Curcumin Attenuates on Carbon Tetrachloride-Induced Acute Liver Injury in Mice
      via Modulation of the Nrf2/HO-1 and TGF-beta1/Smad3 Pathway.
AB  - This study aimed to investigate the protective effect of curcumin against carbon
      tetrachloride (CCl4)-induced acute liver injury in a mouse model, and to explain
      the underlying mechanism. Curcumin at doses of 50, 100 and 200 mg/kg/day were
      administered orally once daily for seven days prior to CCl4 exposure. At 24 h,
      curcumin-attenuated CCl4 induced elevated serum transaminase activities and
      histopathological damage in the mouse's liver. Curcumin pre-treatment at 50, 100
      and 200 mg/kg significantly ameliorated CCl4-induced oxidative stress,
      characterized by decreased malondialdehyde (MDA) formations, and increased
      superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH)
      content, followed by a decrease in caspase-9 and -3 activities. Curcumin pre
      treatment significantly decreased CCl4-induced inflammation. Furthermore,
      curcumin pre-treatment significantly down-regulated the expression of TGF-beta1
      and Smad3 mRNAs (both p < 0.01), and up-regulated the expression of nuclear
      factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (both p < 0.01) in the
      liver. Inhibition of HO-1 attenuated the protective effect of curcumin on CCl4
      induced acute liver injury. Given these outcomes, curcumin could protect against
      CCl4-induced acute liver injury by inhibiting oxidative stress and inflammation,
      which may partly involve the activation of Nrf2/HO-1 and inhibition of TGF
      beta1/Smad3 pathways.

PMID- 29351230
TI  - Comparison of Antioxidative Effects of Insect Tea and Its Raw Tea (Kuding Tea)
      Polyphenols in Kunming Mice.
AB  - Kudingcha is a traditional Chinese tea, and insect tea is a special drink
      produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea
      polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity
      polyphenols extracted by centrifuge precipitation. The present study was designed
      to compare the antioxidative effects of insect tea polyphenols (ITP) and its raw
      tea (Kuding tea) polyphenols (KTP) on d-galactose-induced oxidation in Kunming
      (KM) mice. KM mice were treated with ITP (200 mg/kg) and KTP (200 mg/kg) by
      gavage, and vitamin C (VC, 200 mg/kg) was also used as a positive control by
      gavage. After determination in serum, liver and spleen, ITP-treated mice showed
      higher superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and
      glutathione (GSH) activities and lower nitric oxide (NO), malonaldehyde (MDA)
      activities than VC-treated mice, KTP-treated mice and untreated oxidation mice
      (control group). By H&E section observation, the mice induced by d-galactose
      induced oxidation showed more changes than normal mice, and oxidative damage
      appeared in liver and spleen tissues; ITP, VC and KTP improved oxidative damage
      of liver and spleen tissues, and the effects of ITP were better than VC and KTP.
      Using quantitative polymerase chain reaction (qPCR) and western blot experiments,
      it was observed that ITP could increase the mRNA and protein expression of
      neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS),
      manganese superoxide dismutase (Mn-SOD), cupro/zinc superoxide dismutase (Cu/Zn
      SOD), catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor erythroid 2 related
      factor 2 (Nrf2), gamma glutamylcysteine synthetase (gamma-GCS), and
      NAD(P)H:quinone oxidoreductase 1 (NQO1) and reduce inducible nitric oxide
      synthase (iNOS) expression in liver and spleen tissues compared to the control
      group. These effects were stronger than for VC and KTP. Both ITP and KTP had good
      antioxidative effects, and after the transformation of insects, the effects of
      ITP were better than that of KTP and even better than VC. Thus, ITP can be used
      as an antioxidant and anti-ageing functional food.

PMID- 29351231
TI  - Molecular Network-Based Identification of Competing Endogenous RNAs in Thyroid
      Carcinoma.
AB  - RNAs may act as competing endogenous RNAs (ceRNAs), a critical mechanism in
      determining gene expression regulations in many cancers. However, the roles of
      ceRNAs in thyroid carcinoma remains elusive. In this study, we have developed a
      novel pipeline called Molecular Network-based Identification of ceRNA (MNIceRNA)
      to identify ceRNAs in thyroid carcinoma. MNIceRNA first constructs micro RNA
      (miRNA)-messenger RNA (mRNA)long non-coding RNA (lncRNA) networks from miRcode
      database and weighted correlation network analysis (WGCNA), based on which to
      identify key drivers of differentially expressed RNAs between normal and tumor
      samples. It then infers ceRNAs of the identified key drivers using the long non
      coding competing endogenous database (lnCeDB). We applied the pipeline into The
      Cancer Genome Atlas (TCGA) thyroid carcinoma data. As a result, 598 lncRNAs, 1025
      mRNAs, and 90 microRNA (miRNAs) were inferred to be differentially expressed
      between normal and thyroid cancer samples. We then obtained eight key driver
      miRNAs, among which hsa-mir-221 and hsa-mir-222 were key driver RNAs identified
      by both miRNA-mRNA-lncRNA and WGCNA network. In addition, hsa-mir-375 was
      inferred to be significant for patients' survival with 34 associated ceRNAs,
      among which RUNX2, DUSP6 and SEMA3D are known oncogenes regulating cellular
      proliferation and differentiation in thyroid cancer. These ceRNAs are critical in
      revealing the secrets behind thyroid cancer progression and may serve as future
      therapeutic biomarkers.

PMID- 29351232
TI  - Dietary Acid Load and Potassium Intake Associate with Blood Pressure and
      Hypertension Prevalence in a Representative Sample of the German Adult
      Population.
AB  - Diets rich in fruits and vegetables, like the Dietary Approaches to Stop
      Hypertension (DASH)-diet, are usually characterized by high potassium intake and
      reduced dietary acid load, and have been shown to reduce blood pressure (BP).
      However, the relevance of potential renal acid load (PRAL) for BP has not been
      compared with the relevance to BP of urinary biomarker (K-urine)- and dietary
      food frequency questionnaire (K-FFQ)-based estimates of potassium intake in a
      general adult population sample. For 6788 participants (aged 18-79 years) of the
      representative German Health-Interview and Examination Survey for Adults (DEGS1),
      associations of PRAL, K-urine, and K-FFQ with BP and hypertension prevalence were
      cross-sectionally examined in multivariable linear and logistic regression
      models. PRAL was significantly associated with higher systolic BP (p = 0.0002)
      and higher hypertension prevalence (Odds ratio [OR] high vs. low PRAL = 1.45, p =
      0.0004) in models adjusted for age, sex, body mass index (BMI), estimated sodium
      intake, kidney function, relevant medication, and further important covariates.
      Higher estimates of K-FFQ and K-urine were related to lower systolic BP (p = 0.04
      and p < 0.0001) and lower hypertension prevalence (OR = 0.82, p = 0.04 and OR =
      0.77, p = 0.02) as well as a lower diastolic BP (p = 0.03 and p = 0.0003). Our
      results show, for the first time in a comparative analysis of a large
      representative population sample, significant relationships of BP and
      hypertension prevalence with questionnaire- and biomarker-based estimates of
      potassium intake and with an estimate of dietary acid load.

PMID- 29351233
TI  - Postpartum Women's Perspectives of Engaging with a Dietitian and Exercise
      Physiologist via Video Consultations for Weight Management: A Qualitative
      Evaluation.
AB  - Optimising weight status after childbirth is important. Video consultations are
      an unexplored opportunity to deliver real-time support to postpartum women to
      improve lifestyle behaviours. This study aims to provide insight into postpartum
      women's perspectives of engaging with a dietitian and exercise physiologist
      through video consultations for tailored nutrition and exercise care. A
      qualitative study using individual telephone interviews (13-36 min) was
      undertaken. 21 women (body mass index (BMI): 28.1 +/- 3.8 kg/m2; age: 32.3 +/-
      3.0 years; parity: 1.6 +/- 0.9 children) who had completed the 8 week "Video
      coaching to assist lifestyle (VITAL) change for mums" intervention participation
      included up to five video consultations with a dietitian and exercise
      physiologist. The interviews were audiorecorded and transcribed. Thematic data
      analysis was conducted by an independent researcher using NVIVO11. Themes
      relating to the video consultation experience included feeling that they did not
      differ from other consultations, they were convenient, and the length of time and
      flexible options were appropriate; however there was a desire for increased
      contact frequency. The dietitian and exercise physiologist were perceived to
      increase the participants' knowledge and confidence to improve health behaviours.
      The approach to setting realistic and tailored goals was well received. Tailored
      advice from a dietitian and exercise physiologist received via video
      consultations is acceptable for postpartum women and offers a viable alternative
      to in-person care.

PMID- 29351234
TI  - Contribution of the Ratio of Tocopherol Homologs to the Oxidative Stability of
      Commercial Vegetable Oils.
AB  - The antioxidant activity of tocopherols in vegetable oils was shown to chiefly
      depend on the amount and the tocopherol homolog present. However, the most
      effective ratio of tocopherol homologs with regard to the antioxidant capacity
      has not been elucidated so far. The present study analyzed the effect of
      different tocopherol concentrations, homologs and ratios of homologs on markers
      of lipid oxidation in the most commonly consumed vegetable oils (canola,
      sunflower, soybean oil) stored in a 12 h light/dark cycle at 22 +/- 2  degrees C
      for 56 days under retail/household conditions. After 56 days of storage, the
      alpha-tocopherol-rich canola and sunflower oil showed the strongest rise in lipid
      peroxides, yielding 25.1 +/- 0.03 meq O2/kg (+25.3-fold) and 24.7 +/- 0.05 meq
      O2/kg (+25.0-fold), respectively. ESR experiments, excluding effects of the oils'
      matrices and other minor constituents, confirmed that a food representative
      tocopherol ratio of (gamma + delta)/alpha = 4.77, as represented in soybean oil,
      led to a more pronounced delay of lipid oxidation than a lower ratio in canola
      (1.39) and sunflower oil (0.06). An optimum (gamma + delta)/alpha -tocopherol
      ratio contributing to the oxidative quality of vegetable oils extending their
      shelf life has to be investigated.

PMID- 29351235
TI  - Quadrilateral Micro-Hole Array Machining on Invar Thin Film: Wet Etching and
      Electrochemical Fusion Machining.
AB  - Ultra-precision products which contain a micro-hole array have recently shown
      remarkable demand growth in many fields, especially in the semiconductor and
      display industries. Photoresist etching and electrochemical machining are widely
      known as precision methods for machining micro-holes with no residual stress and
      lower surface roughness on the fabricated products. The Invar shadow masks used
      for organic light-emitting diodes (OLEDs) contain numerous micro-holes and are
      currently machined by a photoresist etching method. However, this method has
      several problems, such as uncontrollable hole machining accuracy, non-etched
      areas, and overcutting. To solve these problems, a machining method that combines
      photoresist etching and electrochemical machining can be applied. In this study,
      negative photoresist with a quadrilateral hole array pattern was dry coated onto
      30-um-thick Invar thin film, and then exposure and development were carried out.
      After that, photoresist single-side wet etching and a fusion method of wet
      etching-electrochemical machining were used to machine micro-holes on the Invar.
      The hole machining geometry, surface quality, and overcutting characteristics of
      the methods were studied. Wet etching and electrochemical fusion machining can
      improve the accuracy and surface quality. The overcutting phenomenon can also be
      controlled by the fusion machining. Experimental results show that the proposed
      method is promising for the fabrication of Invar film shadow masks.

PMID- 29351236
TI  - Trends in Resistance to Extended-Spectrum Cephalosporins and Carbapenems among
      Escherichia coli and Klebsiella spp. Isolates in a District in Western India
      during 2004-2014.
AB  - Surveillance data on the level of resistant bacteria is needed to inform
      strategies to reduce the development and spread of antibiotic resistance. The aim
      of this study was to determine the non-susceptibility trends to extended-spectrum
      cephalosporins and carbapenems among Escherichia coli and Klebsiella spp.
      isolates from the district of Nashik in Western India during the period 2004
      2014. Antibacterial susceptibility testing of clinical isolates was performed
      using Kirby-Bauer disc diffusion method to determine inhibitory zone diameters.
      The change in proportions of non-susceptible bacteria over calendar time was
      investigated with spline transformations in a logistic regression model. For the
      extended-spectrum cephalosporins, the proportions of non-susceptible E. coli and
      Klebsiella spp. isolates were above 78.4% and 84.9% throughout the study period,
      respectively. E. coli and Klebsiella spp. isolates exhibited carbapenem non
      susceptibility levels as high as 76.9% and 84.1% respectively. The proportions of
      extended-spectrum betalactamase (ESBL)-producing isolates ranged from 38.3-85.9%
      in E. coli and from 45.1-93.1% in Klebsiella spp. Significantly higher
      proportions of non-susceptible and ESBL-producing isolates were found among
      isolates from inpatients compared to isolates from outpatients for both E. coli
      and Klebsiella spp. (p < 0.050). The high proportions of non-susceptible isolates
      observed show that there is great need to focus on optimal use of antibiotics to
      reduce the development of antibiotic resistance.

PMID- 29351237
TI  - Bioengineering of rFVIIa Biopharmaceutical and Structure Characterization for
      Biosimilarity Assessment.
AB  - Eptacog alfa (NovoSeven(r)) is a vitamin K-dependent recombinant Factor VIIa
      produced by genetic engineering from baby hamster kidney (BHK) cells as a single
      peptide chain of 406 residues. After activation, it consists of a light chain
      (LC) of 152 amino and a heavy chain (HC) of 254 amino acids. Recombinant FVIIa
      undergoes many post-translational modifications (PTMs). The first ten glutamic
      acids of the N-terminal moiety are gamma-carboxylated, Asn145 and Asn322 are N
      glycosylated, and Ser52 and Ser60 are O-glycosylated. A head-to-head
      biosimilarity study was conducted for the originator and the first biosimilar
      AryoSevenTM to evaluate comparable bioengineering. Physicochemical properties
      were analyzed based on mass spectrometry, including intact mass, PTMs and higher
      order structure. Both biotherapeutics exhibit a batch-to-batch variability in
      their N-glycan profiles. N-Glycopeptide analysis with UHPLC-QTOF-MSE confirmed N
      glycosylation sites as well as two different O-glycopeptide sites. Ser60 was
      found to be O-fucosylated and Ser52 had O-glucose or O-glucose-(xylose)1,2 motifs
      as glycan variants. Ion mobility spectrometry (TWIMS) and NMR spectroscopy data
      affirm close similarity of the higher-order structure of both biologicals.
      Potency of the biodrugs was analyzed by a coagulation assay demonstrating
      comparable bioactivity. Consequently, careful process optimization led to a
      stable production process of the biopharmaceuticals.

PMID- 29351240
TI  - Machine Learning and Infrared Thermography for Fiber Orientation Assessment on
      Randomly-Oriented Strands Parts.
AB  - The use of fiber reinforced materials such as randomly-oriented strands has grown
      in recent years, especially for manufacturing of aerospace composite structures.
      This growth is mainly due to their advantageous properties: they are lighter and
      more resistant to corrosion when compared to metals and are more easily shaped
      than continuous fiber composites. The resistance and stiffness of these materials
      are directly related to their fiber orientation. Thus, efficient approaches to
      assess their fiber orientation are in demand. In this paper, a non-destructive
      evaluation method is applied to assess the fiber orientation on laminates
      reinforced with randomly-oriented strands. More specifically, a method called
      pulsed thermal ellipsometry combined with an artificial neural network, a machine
      learning technique, is used in order to estimate the fiber orientation on the
      surface of inspected parts. Results showed that the method can be potentially
      used to inspect large areas with good accuracy and speed.

PMID- 29351238
TI  - Telomeres: Implications for Cancer Development.
AB  - Telomeres facilitate the protection of natural ends of chromosomes from
      constitutive exposure to the DNA damage response (DDR). This is most likely
      achieved by a lariat structure that hides the linear telomeric DNA through
      protein-protein and protein-DNA interactions. The telomere shortening associated
      with DNA replication in the absence of a compensatory mechanism culminates in
      unmasked telomeres. Then, the subsequent activation of the DDR will define the
      fate of cells according to the functionality of cell cycle checkpoints.
      Dysfunctional telomeres can suppress cancer development by engaging replicative
      senescence or apoptotic pathways, but they can also promote tumour initiation.
      Studies in telomere dynamics and karyotype analysis underpin telomere crisis as a
      key event driving genomic instability. Significant attainment of telomerase or
      alternative lengthening of telomeres (ALT)-pathway to maintain telomere length
      may be permissive and required for clonal evolution of genomically-unstable cells
      during progression to malignancy. We summarise current knowledge of the role of
      telomeres in the maintenance of chromosomal stability and carcinogenesis.

PMID- 29351241
TI  - Molecular Characterization and Expression Profiles of Sp-uchl3 and Sp-uchl5
      during Gonad Development of Scylla paramamosain.
AB  - Ubiquitin C-terminal hydrolases (UCHLs) are a subset of deubiquitinating enzymes,
      and are involved in numerous physiological processes. However, the role of UCHLs
      during gonad development has not been studied in crustaceans. In this study, we
      have first cloned and analyzed expression profiling of Sp-uchl3 and Sp-uchl5
      genes from mud crab Scylla paramamosain. The full-length cDNA of Sp-uchl3 is of
      1804 bp. Its expression level in the ovary was significantly higher than in other
      tissues (p < 0.01), and during gonadal development, its expression in both O1 and
      O5 stages was significantly higher than in the other three stages of ovaries (p <
      0.05), while in T3 it was higher than in the former two stages of testes (p <
      0.05). Meanwhile, the full-length cDNA of Sp-UCHL5 is 1217 bp. The expression
      level in the ovary was significantly higher than in other tissues (p < 0.01). Its
      expression in ovaries was higher than in testes during gonadal development (p <
      0.05). The expression level in the O5 stage was the highest, followed by the O3
      stage in ovarian development, and with no significant difference in the testis
      development (p > 0.05). These results provide basic data showing the role of Sp
      UCHL3 and Sp-UCHL5 in the gonad development of the crab.

PMID- 29351243
TI  - Awake versus Asleep Deep Brain Stimulation Surgery: Technical Considerations and
      Critical Review of the Literature.
AB  - Advancements in neuroimaging have led to a trend toward direct, image-based
      targeting under general anesthesia without the use of microelectrode recording
      (MER) or intraoperative test stimulation, also referred to as "asleep" deep brain
      stimulation (DBS) surgery. Asleep DBS, utilizing imaging in the form of
      intraoperative computed tomography (iCT) or magnetic resonance imaging (iMRI),
      has demonstrated reliable targeting accuracy of DBS leads implanted within the
      globus pallidus and subthalamic nucleus while also improving clinical outcomes in
      patients with Parkinson's disease. In lieu, of randomized control trials,
      retrospective comparisons between asleep and awake DBS with MER have shown
      similar short-term efficacy with the potential for decreased complications in
      asleep cohorts. In lieu of long-term outcome data, awake DBS using MER must
      demonstrate more durable outcomes with fewer stimulation-induced side effects and
      lead revisions in order for its use to remain justifiable; although patient
      specific factors may also be used to guide the decision regarding which technique
      may be most appropriate and tolerable to the patient.

PMID- 29351244
TI  - School Contextual Features of Social Disorder and Mental Health Complaints-A
      Multilevel Analysis of Swedish Sixth-Grade Students.
AB  - This study addressed school-contextual features of social disorder in relation to
      sixth-grade students' experiences of bullying victimization and mental health
      complaints. It investigated, firstly, whether the school's concentrations of
      behavioural problems were associated with individual students' likelihood of
      being bullied, and secondly, whether the school's concentrations of behavioural
      problems and bullying victimization predicted students' emotional and
      psychosomatic health complaints. The data were derived from the Swedish National
      Survey of Mental Health among Children and Young People, carried out among sixth
      grade students (approximately 12-13 years old) in Sweden in 2009. The analyses
      were based on information from 59,510 students distributed across 1999 schools.
      The statistical method used was multilevel modelling. While students' own
      behavioural problems were associated with an elevated risk of being bullied,
      attending a school with a higher concentration of students with behavioural
      problems also increased the likelihood of being bullied. Attending a school with
      higher levels of bullying victimization and behavioural problems predicted more
      emotional and psychosomatic complaints, even when adjusting for their individual
      level analogues. The findings indicate that school-level features of social
      disorder influence bullying victimization and mental health complaints among
      students.

PMID- 29351242
TI  - "Vessels in the Storm": Searching for Prognostic and Predictive Angiogenic
      Factors in Colorectal Cancer.
AB  - High expectations are placed upon anti-angiogenic compounds for metastatic
      colorectal cancer (mCRC), the first malignancy for which such type of treatment
      has been approved. Indeed, clinical trials have confirmed that targeting the
      formation of new vessels can improve in many cases clinical outcomes of mCRC
      patients. However, current anti-angiogenic drugs are far from obtaining the
      desirable or expected curative results. Many are the factors probably involved in
      such disappointing results, but particular attention is currently focused on the
      validation of biomarkers able to improve the direction of treatment protocols.
      Because clinical studies have clearly demonstrated that serum or tissue
      concentration of some angiogenic factors is associated with the evolution of the
      disease of mCRC patients, they are currently explored as potential biomarkers of
      prognosis and of tumor response to therapy. However, the complex biology
      underlying CRC -induced angiogenesis is a hurdle in finding rapid solutions. The
      aim of this review was to explore molecular mechanisms that determine the
      formation of tumor-associated vessels during CRC progression, and to discuss the
      potential role of angiogenic factors as diagnostic, prognostic and predictive
      biomarkers in CRC.

PMID- 29351245
TI  - Exposure to Ambient Air Particles Increases the Risk of Mental Disorder: Findings
      from a Natural Experiment in Beijing.
AB  - Epidemiology studies indicated that air pollution has been associated with
      adverse neurological effects in human. Moreover, the secretion of glucocorticoid
      (GC) affects the mood regulation, and the negative feedback of hippocampal
      glucocorticoid receptors (GR) inhibits the GC secretion. Meanwhile, the over
      secretion of GC can interfere the immune system and induce neurotoxicity. In the
      present study, the human test showed that the secretion of the cortisol in plasma
      was elevated after exposure in heavy air pollution. In the mouse model, we found
      that breathing the highly polluted air resulted in the negative responses of the
      mood-related behavioral tests and morphology of hippocampus, as well as the over
      secretion of GC in plasma, down regulation of GR, and up-regulation of cytokine
      and chemokine in the hippocampus. When considering the interrelated trends
      between the hippocampal GR, inflammatory factors, and plasmatic GC, we speculated
      that PM2.5 exposure could lead to the increased secretion of GC in plasma by
      decreasing the expression of GR in hippocampus, which activated the inflammation
      response, and finally induced neurotoxicity, suggesting that PM2.5 exposure
      negatively affects mood regulation. When combined with the results of the human
      test, it indicated that exposure to ambient air particles increased the risk of
      mental disorder.

PMID- 29351246
TI  - Addition of Berberine to Preservation Solution in an Animal Model of Ex Vivo
      Liver Transplant Preserves Mitochondrial Function and Bioenergetics from the
      Damage Induced by Ischemia/Reperfusion.
AB  - Liver transplantation is a therapeutic regimen to treat patients with non
      malignant end-stage liver diseases and malignant tumors of hepatic origin. The
      ischemia/reperfusion (I/R) injury in liver transplantation is associated with
      disruption of mitochondrial function in the hepatic parenchyma. Several studies
      have been conducted in animal models to identify pharmacological therapeutic
      strategies to minimize the injury induced by the cold/warm I/R in liver
      transplantation. Most of these studies were conducted in unrealistic conditions
      without the potential to be translated to clinical usage. Berberine (BBR) is a
      pharmacological compound with a potential protective effect of the mitochondrial
      function in the context of I/R. For the future clinical application of these
      pharmacological strategies, it is essential that a close resemblance exists
      between the methodology used in the animals models and real life. In this study,
      we have demonstrated that the addition of BBR to the preservation solution in an
      I/R setting preserves mitochondrial function and bioenergetics, protecting the
      liver from the deleterious effects caused by I/R. As such, BBR has the potential
      to be used as a pharmacological therapeutic strategy.

PMID- 29351247
TI  - B Type and Complex A/B Type Epicatechin Trimers Isolated from Litchi pericarp
      Aqueous Extract Show High Antioxidant and Anticancer Activity.
AB  - Litchi (Litchi chinensis Sonn.) fruit is known for its rich source of phenolics.
      Litchi pericarp contains high levels of epicatechin that may form oligomers of
      various lengths. Except for several A or B type epicatechin dimers, other soluble
      oligomers have rarely been identified in the pericarp. Here, bioassay-guided
      column fractionation was applied to isolate bioactive phenolics from aqueous
      pericarp extract. A fraction (S3) was obtained by two rounds of Sephadex LH-20
      column chromatography, and showed higher antioxidant activity and inhibition on
      the proliferation of human lung cancer cells (A549) than Litchi anthocyanins. S3
      was further separated to isolate fractions P1-P4, which all showed higher
      antioxidant activity than vitamin C. P3 showed 32.9% inhibition on A549 cells at
      30 MUg/mL, higher than other fractions and cis-Dichlorodiamineplatinum (DDP, 0.5
      MUg/mL), but not as high as the combination of the four fractions. Using HPLC-Q
      TOF-MS/MS, one B-type and complex A/B type epicatechin trimers were identified in
      P3; another B-type and two A/B-type trimers were identified in P4. P1 and P2,
      containing epicatechin and proanthocyanidin B2, respectively, showed no cell
      inhibition at 30 MUg/mL. It is the first time that the two B type trimers of
      epicatechins (Litchitannin B1 and B2), have been found in Litchi species. The
      identified proanthocyanidins were detected in the pericarp of the young fruit,
      and the levels of the compounds decreased as the fruit developed, correlating to
      the decreasing patterns of the expression of LcLAR and LcANR, two key genes in
      the catechin biosynthesis pathway.

PMID- 29351248
TI  - A Comprehensive Study of a Micro-Channel Heat Sink Using Integrated Thin-Film
      Temperature Sensors.
AB  - A micro-channel heat sink is a promising cooling method for high power integrated
      circuits (IC). However, the understanding of such a micro-channel device is not
      sufficient, because the tools for studying it are very limited. The details
      inside the micro-channels are not readily available. In this letter, a micro
      channel heat sink is comprehensively studied using the integrated temperature
      sensors. The highly sensitive thin film temperature sensors can accurately
      monitor the temperature change in the micro-channel in real time. The outstanding
      heat dissipation performance of the micro-channel heat sink is proven in terms of
      maximum temperature, cooling speed and heat resistance. The temperature profile
      along the micro-channel is extracted, and even small temperature perturbations
      can be detected. The heat source formed temperature peak shifts towards the flow
      direction with the increasing flow rate. However, the temperature non-uniformity
      is independent of flow rate, but solely dependent on the heating power. Specific
      designs for minimizing the temperature non-uniformity are necessary. In addition,
      the experimental results from the integrated temperature sensors match the
      simulation results well. This can be used to directly verify the modeling
      results, helping to build a convincing simulation model. The integrated sensor
      could be a powerful tool for studying the micro-channel based heat sink.

PMID- 29351250
TI  - A GPS Phase-Locked Loop Performance Metric Based on the Phase Discriminator
      Output.
AB  - We propose a novel GPS phase-lock loop (PLL) performance metric based on the
      standard deviation of tracking error (defined as the discriminator's estimate of
      the true phase error), and explain its advantages over the popular phase jitter
      metric using theory, numerical simulation, and experimental results. We derive an
      augmented GPS phase-lock loop (PLL) linear model, which includes the effect of
      coherent averaging, to be used in conjunction with this proposed metric. The
      augmented linear model allows more accurate calculation of tracking error
      standard deviation in the presence of additive white Gaussian noise (AWGN) as
      compared to traditional linear models. The standard deviation of tracking error,
      with a threshold corresponding to half of the arctangent discriminator pull-in
      region, is shown to be a more reliable/robust measure of PLL performance under
      interference conditions than the phase jitter metric. In addition, the augmented
      linear model is shown to be valid up until this threshold, which facilitates
      efficient performance prediction, so that time-consuming direct simulations and
      costly experimental testing can be reserved for PLL designs that are much more
      likely to be successful. The effect of varying receiver reference oscillator
      quality on the tracking error metric is also considered.

PMID- 29351249
TI  - Utilizing Dietary Micronutrient Ratios in Nutritional Research May be More
      Informative than Focusing on Single Nutrients.
AB  - The 2015 US dietary guidelines advise the importance of good dietary patterns for
      health, which includes all nutrients. Micronutrients are rarely, if ever,
      consumed separately, they are not tissue specific in their actions and at the
      molecular level they are multitaskers. Metabolism functions within a seemingly
      random cellular milieu however ratios are important, for example, the ratio of
      adenosine triphosphate to adenosine monophosphate, or oxidized to reduced
      glutathione. Health status is determined by simple ratios, such as the waist hip
      ratio, or ratio of fat mass to lean mass. Some nutrient ratios exist and remain
      controversial such as the omega-6/omega-3 fatty acid ratio and the
      sodium/potassium ratio. Therefore, examining ratios of micronutrients may convey
      more information about how diet and health outcomes are related. Summarized
      micronutrient intake data, from food only, from the National Health and Nutrition
      Examination Survey, were used to generate initial ratios. Overall, in this
      preliminary analysis dietary ratios of micronutrients showed some differences
      between intakes and recommendations. Principles outlined here could be used in
      nutritional epidemiology and in basic nutritional research, rather than focusing
      on individual nutrient intakes. This paper presents the concept of micronutrient
      ratios to encourage change in the way nutrients are regarded.

PMID- 29351251
TI  - Compatibility with Panax notoginseng and Rehmannia glutinosa Alleviates the
      Hepatotoxicity and Nephrotoxicity of Tripterygium wilfordii via Modulating the
      Pharmacokinetics of Triptolide.
AB  - Tripterygium wilfordii (TW) and the representative active component triptolide
      show positive therapeutic effect on the autoimmune disorders and simultaneously
      ineluctable hepatotoxicity and nephrotoxicity. Combinational application of Panax
      notoginseng (PN) and Rehmannia glutinosa (RG) weakens the toxicity of TW
      according the clinical application of traditional Chinese medicine. This article
      was aimed at the mechanism of decreasing toxicity of TW by the combinational
      application of PN and RG. Biochemical and pathohistological analysis were
      utilized to assess the toxicity on liver and kidney in rats administrated with
      TW, TW-PN, TW-RG and TW-PN-RG for 3 and 7 days. Meanwhile, the pharmacokinetics
      profiling of triptolide and wilforlide A was determined based on the plasma
      concentration analyzed by ultra-high performance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS). TW-induced alkaline phosphatase (ALP), the marker
      for liver injury, was enhanced from 22.83 +/- 1.29 to 40.73 +/- 1.42 King's
      unit/100 mL (p < 0.01) at day 7. TW-PN-RG decreased the serum ALP of TW-treated
      rats at 30.15 +/- 1.27 King's unit/100 mL (p < 0.01). For nephrotoxicity, TW
      pronouncedly elevated serum creatinine (SCr) in rats from 20.33 +/- 1.77 to 49.82
      +/- 2.35 MUmol/L (p < 0.01). However, rats treated with TW-PN-RG showed lower SCr
      at 30.48 +/- 1.98 MUmol/L (p < 0.01). Moreover, TW-PN-RG significantly decreased
      the TW-induced elevation of total bilirubin (T-BIL), alanine amino transferase
      (ALT), aspartate amino transferase (AST), blood urea nitrogen (Bun), and reversed
      the TW-resulted pathohistological characteristics of liver and kidney. The
      delayed time to reach Cmax (Tmax) and reduced maximum concentration (Cmax) and
      area under plasma concentration-time curve (AUC) of triptolide and wilforlide A
      were explored in rats with combinational formulas. Synergism of PN and RG
      obviously prolonged the half-life (t1/2) and apparent volume of distribution
      (Vd), but exerted no action on the clearance rate. The compatibility of TW, PN
      and RG influences intracorporal process of both triptolide and wilforlide A on
      the steps of absorption and tissue distribution contributing to less toxicity of
      TW on liver and kidney.

PMID- 29351252
TI  - Comparison of Binding Affinities of Water-Soluble Calixarenes with the
      Organophosphorus Nerve Agent Soman (GD) and Commonly-Used Nerve Agent Simulants.
AB  - The formation of inclusion complexes of the water-soluble p
      sulfonatocalix[n]arenes, where n = 4 or 6, with the Chemical Warfare Agent (CWA)
      GD, or Soman, and commonly used dialkyl methylphosphonate simulants has been
      studied by experimental solution NMR methods and by Molecular Mechanics (MMFF)
      and semi-empirical (PM6) calculations. Complex formation in non-buffered and
      buffered solutions is driven by the hydrophobic effect, and complex stoichiometry
      determined as 1:1 for all host:guest pairs. Low affinity complexes (Kassoc < 100
      M-1) are observed for all guests, attributed to poor host-guest complementarity
      and the role of buffer cation species accounts for the low affinity of the
      complexes. Comparison of CWA and simulant behavior adds to understanding of CWA
      simulant correlations and the challenges of simulant selection.

PMID- 29351254
TI  - Bridge Structure Deformation Prediction Based on GNSS Data Using Kalman-ARIMA
      GARCH Model.
AB  - Bridges are an essential part of the ground transportation system. Health
      monitoring is fundamentally important for the safety and service life of bridges.
      A large amount of structural information is obtained from various sensors using
      sensing technology, and the data processing has become a challenging issue. To
      improve the prediction accuracy of bridge structure deformation based on data
      mining and to accurately evaluate the time-varying characteristics of bridge
      structure performance evolution, this paper proposes a new method for bridge
      structure deformation prediction, which integrates the Kalman filter,
      autoregressive integrated moving average model (ARIMA), and generalized
      autoregressive conditional heteroskedasticity (GARCH). Firstly, the raw
      deformation data is directly pre-processed using the Kalman filter to reduce the
      noise. After that, the linear recursive ARIMA model is established to analyze and
      predict the structure deformation. Finally, the nonlinear recursive GARCH model
      is introduced to further improve the accuracy of the prediction. Simulation
      results based on measured sensor data from the Global Navigation Satellite System
      (GNSS) deformation monitoring system demonstrated that: (1) the Kalman filter is
      capable of denoising the bridge deformation monitoring data; (2) the prediction
      accuracy of the proposed Kalman-ARIMA-GARCH model is satisfactory, where the mean
      absolute error increases only from 3.402 mm to 5.847 mm with the increment of the
      prediction step; and (3) in comparision to the Kalman-ARIMA model, the Kalman
      ARIMA-GARCH model results in superior prediction accuracy as it includes partial
      nonlinear characteristics (heteroscedasticity); the mean absolute error of five
      step prediction using the proposed model is improved by 10.12%. This paper
      provides a new way for structural behavior prediction based on data processing,
      which can lay a foundation for the early warning of bridge health monitoring
      system based on sensor data using sensing technology.

PMID- 29351253
TI  - The Role of Sugar Transporter Genes during Early Infection by Root-Knot
      Nematodes.
AB  - Although pathogens such as nematodes are known to hijack nutrients from host
      plants, the mechanisms whereby nematodes obtain sugars from plants remain largely
      unknown. To determine the effects of nematode infection on host plant sugar
      allocation, soluble sugar (fructose, glucose, sucrose) content was investigated
      using high-performance liquid chromatography with refractive index detection and
      was found to increase significantly in tomato (Solanum lycopersicum, Sl) leaves
      and roots during early infection by root-knot nematodes (RKNs). To further
      analyze whether sugar transporters played a role in this process, the expression
      levels of sucrose transporter (SUT/SUC), Sugars Will Eventually be Exported
      Transporter (SWEET), tonoplast monosaccharide transporter (TMT), and vacuolar
      glucose transporter (VGT) gene family members were examined by qRT-PCR analysis
      after RKN infection. The results showed that three SlSUTs, 17 SlSWEETs, three
      SlTMTs, and SlVGT1 were upregulated in the leaves, whereas three SlSUTs, 17
      SlSWEETs, two SlTMTs, and SlVGT1 were induced in the roots. To determine the
      function of the sugar transporters in the RKN infection process, we examined post
      infection responses in the Atsuc2 mutant and pAtSUC2-GUS lines. beta
      glucuronidase expression was strongly induced at the infection sites, and RKN
      development was significantly arrested in the Atsuc2 mutant. Taken together, our
      analyses provide useful information for understanding the sugar transporter
      responses during early infection by RKNs in tomato.

PMID- 29351255
TI  - Game-Theoretical Design of an Adaptive Distributed Dissemination Protocol for
      VANETs.
AB  - Road safety applications envisaged for Vehicular Ad Hoc Networks (VANETs) depend
      largely on the dissemination of warning messages to deliver information to
      concerned vehicles. The intended applications, as well as some inherent VANET
      characteristics, make data dissemination an essential service and a challenging
      task in this kind of networks. This work lays out a decentralized stochastic
      solution for the data dissemination problem through two game-theoretical
      mechanisms. Given the non-stationarity induced by a highly dynamic topology,
      diverse network densities, and intermittent connectivity, a solution for the
      formulated game requires an adaptive procedure able to exploit the environment
      changes. Extensive simulations reveal that our proposal excels in terms of number
      of transmissions, lower end-to-end delay and reduced overhead while maintaining
      high delivery ratio, compared to other proposals.

PMID- 29351256
TI  - Immobilization of Staphylococcus aureus Sortase A on Chitosan Particles and Its
      Applications in Peptide-to-Peptide Ligation and Peptide Cyclization.
AB  - Chitosan macro-particles prepared by the neutralization method were applied to
      Sortase A (SrtA) immobilization using glutaraldehyde as a crosslinking agent. The
      particles were characterized by Fourier transform infrared spectroscopy (FTIR)
      and scanning electron microscopy (SEM). Response surface methodology (RSM) was
      employed to optimize the immobilization process. An average specific activity of
      3142 U (mg protein)-1 was obtained under optimized immobilization conditions
      (chitosan concentration 3%, SrtA concentration 0.5 mg.mL-1, glutaraldehyde
      concentration 0.5%, crosslinking and immobilization at 20  degrees C,
      crosslinking for 3 h, and an immobilization time of 8 h). The transpeptidase
      activity of immobilized SrtA was proved by a peptide-to-peptide ligation with a
      conversion yield approximately at 80%, and the immobilized catalyst was
      successfully reused for five cycles without obvious activity loss. Moreover, the
      scale-up capability of using immobilized SrtA to catalyze a head-to-tail peptide
      cyclization was investigated in a batch reaction and the conversion yield was
      more than 95% when using 20 mg of peptide as a substrate.

PMID- 29351257
TI  - Modifications in the Consumption of Energy, Sugar, and Saturated Fat among the
      Mexican Adult Population: Simulation of the Effect When Replacing Processed Foods
      that Comply with a Front of Package Labeling System.
AB  - A Mexican Committee of Nutrition Experts (MCNE) from the National Institute of
      Public Health (INSP), free from conflict of interest, established food content
      standards to place the front-of-package (FOP) logo on foods that meet these
      nutrition criteria. The objectives were to simulate the effect on nutrient intake
      in the Mexican adult population (20-59 years old) after replacing commonly
      consumed processed foods with those that meet the FOP nutrition-labeling
      criteria. Twenty-four hour dietary recalls were collected from the 2012 Mexican
      National Health and Nutrition Survey (n = 2164 adults). A food database from the
      INSP was used. Weighted medians and 25-75 inter-quartile ranges (IQR) of energy
      and nutrient intake were calculated for all subjects by sociodemographic
      characteristics before and after replacing foods. Significant decreases were
      observed in energy (-5.4%), saturated fatty acids (-18.9%), trans-fatty acids (
      20%), total sugar (-36.8%) and sodium (-10.7%) intake and a significant increase
      in fiber intake (+15.5%) after replacing foods, using the MCNE nutrition
      criteria. Replacing commonly consumed processed foods in the diet with foods that
      meet the FOP nutrition-labeling criteria set by the MCNE can lead to improvements
      in energy and nutrient intake in the Mexican adult population.

PMID- 29351258
TI  - A Polymer Optical Fiber Temperature Sensor Based on Material Features.
AB  - This paper presents a polymer optical fiber (POF)-based temperature sensor. The
      operation principle of the sensor is the variation in the POF mechanical
      properties with the temperature variation. Such mechanical property variation
      leads to a variation in the POF output power when a constant stress is applied to
      the fiber due to the stress-optical effect. The fiber mechanical properties are
      characterized through a dynamic mechanical analysis, and the output power
      variation with different temperatures is measured. The stress is applied to the
      fiber by means of a 180 degrees  curvature, and supports are positioned on the
      fiber to inhibit the variation in its curvature with the temperature variation.
      Results show that the sensor proposed has a sensitivity of 1.04 * 10-3  degrees C
      1, a linearity of 0.994, and a root mean squared error of 1.48  degrees C, which
      indicates a relative error of below 2%, which is lower than the ones obtained for
      intensity-variation-based temperature sensors. Furthermore, the sensor is able to
      operate at temperatures up to 110  degrees C, which is higher than the ones
      obtained for similar POF sensors in the literature.

PMID- 29351259
TI  - Dietary Fatty Acids Alter Lipid Profiles and Induce Myocardial Dysfunction
      without Causing Metabolic Disorders in Mice.
AB  - Oversupply of bulk saturated fatty acids (SFA) induces metabolic disorders and
      myocardial dysfunction. We investigated whether, without causing metabolic
      disorders, the uptake of individual dietary SFA species alters lipid profiles and
      induces myocardial dysfunction. C57BL/6 mice were fed various customized long
      chain SFA diets (40% caloric intake from SFA), including a beef tallow (HBD),
      cocoa butter (HCD), milk fat (HMD) and palm oil diet (HPD), for 6 months. An
      isocaloric fat diet, containing medium-chain triglycerides, served as a control
      (CHD). Long-term intake of dietary long-chain SFA differentially affected the
      fatty acid composition in cardiac phospholipids. All long-chain SFA diets
      increased the levels of arachidonic acid and total SFA in cardiac phospholipids.
      The preferential incorporation of individual SFA into the cardiac phospholipid
      fraction was dependent on the dietary SFA species. Cardiac ceramide content was
      elevated in all mice fed long-chain SFA diets, while cardiac hypertrophy was only
      presented in mice fed HMD or HPD. We have demonstrated that the intake of long
      chain SFA species differentially alters cardiac lipid profiles and induces
      cardiac dysfunction, without causing remarkable metabolic disorders.

PMID- 29351261
TI  - Three-Dimensional Terahertz Coded-Aperture Imaging Based on Single Input Multiple
      Output Technology.
AB  - As a promising radar imaging technique, terahertz coded-aperture imaging (TCAI)
      can achieve high-resolution, forward-looking, and staring imaging by producing
      spatiotemporal independent signals with coded apertures. In this paper, we
      propose a three-dimensional (3D) TCAI architecture based on single input multiple
      output (SIMO) technology, which can reduce the coding and sampling times sharply.
      The coded aperture applied in the proposed TCAI architecture loads either
      purposive or random phase modulation factor. In the transmitting process, the
      purposive phase modulation factor drives the terahertz beam to scan the divided
      3D imaging cells. In the receiving process, the random phase modulation factor is
      adopted to modulate the terahertz wave to be spatiotemporally independent for
      high resolution. Considering human-scale targets, images of each 3D imaging cell
      are reconstructed one by one to decompose the global computational complexity,
      and then are synthesized together to obtain the complete high-resolution image.
      As for each imaging cell, the multi-resolution imaging method helps to reduce the
      computational burden on a large-scale reference-signal matrix. The experimental
      results demonstrate that the proposed architecture can achieve high-resolution
      imaging with much less time for 3D targets and has great potential in
      applications such as security screening, nondestructive detection, medical
      diagnosis, etc.

PMID- 29351260
TI  - Fatty Acid Based Microemulsions to Combat Ophthalmia Neonatorum Caused by
      Neisseria gonorrhoeae and Staphylococcus aureus.
AB  - The bacterial species Neisseria gonorrhoeae (N. gonorrhoeae) and Staphylococcus
      aureus (S. aureus) are amongst the main microorganisms that cause ophthalmia
      neonatorum. The current treatment involves the use of various antibiotics such as
      ciprofloxacin, cephalosporin, ceftriaxone and cefotaxime. However, this treatment
      strategy is becoming more ineffective due to the antibiotic resistance in N.
      gonorrhoeae. The current study explores the potential use of fatty acid based
      microemulsions (ME) to prevent N. gonorrhoeae and S. aureus infections in new
      borns' eyes without harmful side effects such as corneal or conjunctiva
      irritation. Pseudo-ternary phase diagrams were constructed to evaluate
      microemulsion regions and six different alpha-linolenic acid based microemulsions
      were prepared. The prepared formulations were characterized for alpha-linolenic
      acid content, size, transparency, zeta potential, Polarized light Microscopy,
      antimicrobial activity and ex vivo ocular toxicity. The mean droplet size of the
      ME formulations was in the range of 190.4 to 350.5 nm and polydispersity index
      (PDI) values were in the range of 0.102 to 0.561. All formulations were found
      stable upon storage for at least 8 weeks. In addition, self-diffusion
      coefficients determined by nuclear magnetic resonance (NMR) reflected that the
      diffusability of water increased at higher than 30% w/w water, while that of
      fatty acids and surfactants was in reverse. The antimicrobial efficacy of
      microemulsions was determined against N. gonorrhoeae and S. aureus. It was
      concluded that all microemulsions have strong antimicrobial effects against N.
      gonorrhoeae and S. aureus. Finally, bovine corneal opacity permeability (BCOP)
      and hen's egg chorioallantoic (HET-CAM) tests results showed that all
      microemulsion formulations were not strong ocular irritants.

PMID- 29351262
TI  - IMU-to-Segment Assignment and Orientation Alignment for the Lower Body Using Deep
      Learning.
AB  - Human body motion analysis based on wearable inertial measurement units (IMUs)
      receives a lot of attention from both the research community and the and
      industrial community. This is due to the significant role in, for instance,
      mobile health systems, sports and human computer interaction. In sensor based
      activity recognition, one of the major issues for obtaining reliable results is
      the sensor placement/assignment on the body. For inertial motion capture (joint
      kinematics estimation) and analysis, the IMU-to-segment (I2S) assignment and
      alignment are central issues to obtain biomechanical joint angles. Existing
      approaches for I2S assignment usually rely on hand crafted features and shallow
      classification approaches (e.g., support vector machines), with no agreement
      regarding the most suitable features for the assignment task. Moreover,
      estimating the complete orientation alignment of an IMU relative to the segment
      it is attached to using a machine learning approach has not been shown in
      literature so far. This is likely due to the high amount of training data that
      have to be recorded to suitably represent possible IMU alignment variations. In
      this work, we propose online approaches for solving the assignment and alignment
      tasks for an arbitrary amount of IMUs with respect to a biomechanical lower body
      model using a deep learning architecture and windows of 128 gyroscope and
      accelerometer data samples. For this, we combine convolutional neural networks
      (CNNs) for local filter learning with long-short-term memory (LSTM) recurrent
      networks as well as generalized recurrent units (GRUs) for learning time dynamic
      features. The assignment task is casted as a classification problem, while the
      alignment task is casted as a regression problem. In this framework, we
      demonstrate the feasibility of augmenting a limited amount of real IMU training
      data with simulated alignment variations and IMU data for improving the
      recognition/estimation accuracies. With the proposed approaches and final models
      we achieved 98.57% average accuracy over all segments for the I2S assignment task
      (100% when excluding left/right switches) and an average median angle error over
      all segments and axes of 2 . 91 for the I2S alignment task.

PMID- 29351263
TI  - Twenty-Nine New Limonoids with Skeletal Diversity from the Mangrove Plant,
      Xylocarpus moluccensis.
AB  - Twenty-nine new limonoids-named xylomolins A1-A7, B1-B2, C1-C2, D-F, G1-G5, H-I,
      J1-J2, K1-K2, L1-L2, and M-N, were isolated from the seeds of the mangrove plant,
      Xylocarpus moluccensis. Compounds 1-13 are mexicanolides with one double bond or
      two conjugated double bonds, while 14 belongs to a small group of mexicanolides
      with an oxygen bridge between C1 and C8. Compounds 15-19 are khayanolides
      containing a Delta8,14 double bond, whereas 20 and 21 are rare khayanolides
      containing a Delta14,15 double bond and Delta8,9, Delta14,15 conjugated double
      bonds, respectively. Compounds 22 and 23 are unusual limonoids possessing a (Z)
      bicyclo[5.2.1]dec-3-en-8-one motif, while 24 and 25 are 30-ketophragmalins with
      Delta8,9, Delta14,15 conjugated double bonds. Compounds 26 and 27 are phragmalin
      8,9,30-ortho esters, whereas 28 and 29 are azadirone and andirobin derivatives,
      respectively. The structures of these compounds, including absolute
      configurations of 15-19, 21-23, and 26, were established by HRESIMS, extensive 1D
      and 2D NMR investigations, and the comparison of experimental electronic circular
      dichroism (ECD) spectra. The absolute configuration of 1 was unequivocally
      established by single-crystal X-ray diffraction analysis, obtained with Cu Kalpha
      radiation. The diverse cyclization patterns of 1-29 reveal the strong flexibility
      of skeletal plasticity in the limonoid biosynthesis of X. moluccensis. Compound
      23 exhibited weak antitumor activity against human triple-negative breast MD-MBA
      231 cancer cells with an IC50 value of 37.7 MUM. Anti-HIV activities of 1, 3, 8,
      10, 11, 14, 20, 23-25, and 27 were tested in vitro. However, no compounds showed
      potent inhibitory activity.

PMID- 29351264
TI  - Identification of Cyclic Dipeptides from Escherichia coli as New Antimicrobial
      Agents against Ralstonia Solanacearum.
AB  - Ralstonia solanacearum is a causative agent of bacterial wilt in many important
      crops throughout the world. How to control bacterial wilt caused by R.
      solanacearum is a major problem in agriculture. In this study, we aim to isolate
      the biocontrol agents that have high efficacy in the control of bacterial wilt.
      Three new bacterial strains with high antimicrobial activity against R.
      solanacearum GMI1000 were isolated and identified. Our results demonstrated that
      these bacteria could remarkably inhibit the disease index of host plant infected
      by R. solanacearum. It was indicated that strain GZ-34 (CCTCC No. M 2016353)
      showed an excellent protective effect to tomato under greenhouse conditions.
      Strain GZ-34 was characterized as Escherichia coli based on morphology,
      biochemistry, and 16S rRNA analysis. We identified that the main antimicrobial
      compounds produced by E. coli GZ-34 were cyclo(l-Pro-d-Ile) and cyclo(l-Pro-l
      Phe) using electrospray ionization mass spectrometry (ESI-MS) and nuclear
      magnetic resonance (NMR) analysis. The two active compounds also interfered with
      the expression levels of some pathogenicity-contributors of R. solanacearum.
      Furthermore, cyclo(l-Pro-l-Phe) effectively inhibited spore formation of
      Magnaporthe grisea, which is a vital pathogenesis process of the fungal pathogen,
      suggesting cyclic dipeptides from E. coli are promising potential antimicrobial
      agents with broad-spectrum activity to kill pathogens or interfere with their
      pathogenesis.

PMID- 29351265
TI  - Development of Antimicrobial Biocomposite Films to Preserve the Quality of Bread.
AB  - This study focused on the development of gelatin-based films with incorporation
      of microcrystalline cellulose as reinforcement material. Clove (Syzygium
      aromaticum), nutmeg (Myristica fragrans), and black pepper (Piper nigrum)
      oleoresins containing antimicrobial compounds of natural origin were incorporated
      into the films. The mechanical, thermal, optical, and structural properties, as
      well as color, seal strength and permeability to water vapor, light, and oil of
      the films were determined. Adding oleoresins to the gelatin matrix increased the
      elongation of the material and significantly diminished its permeability to water
      vapor and oil. Evaluation of the potential use of films containing different
      oleoresins as bread packaging material was influenced by the film properties. The
      biocomposite film containing oleoresin from black pepper was the most effective
      packaging material for maintaining bread's quality characteristics.

PMID- 29351266
TI  - From Extraction of Local Structures of Protein Energy Landscapes to Improved
      Decoy Selection in Template-Free Protein Structure Prediction.
AB  - Due to the essential role that the three-dimensional conformation of a protein
      plays in regulating interactions with molecular partners, wet and dry
      laboratories seek biologically-active conformations of a protein to decode its
      function. Computational approaches are gaining prominence due to the labor and
      cost demands of wet laboratory investigations. Template-free methods can now
      compute thousands of conformations known as decoys, but selecting native
      conformations from the generated decoys remains challenging. Repeatedly, research
      has shown that the protein energy functions whose minima are sought in the
      generation of decoys are unreliable indicators of nativeness. The prevalent
      approach ignores energy altogether and clusters decoys by conformational
      similarity. Complementary recent efforts design protein-specific scoring
      functions or train machine learning models on labeled decoys. In this paper, we
      show that an informative consideration of energy can be carried out under the
      energy landscape view. Specifically, we leverage local structures known as basins
      in the energy landscape probed by a template-free method. We propose and compare
      various strategies of basin-based decoy selection that we demonstrate are
      superior to clustering-based strategies. The presented results point to further
      directions of research for improving decoy selection, including the ability to
      properly consider the multiplicity of native conformations of proteins.

PMID- 29351267
TI  - Motorcycle That See: Multifocal Stereo Vision Sensor for Advanced Safety Systems
      in Tilting Vehicles.
AB  - Advanced driver assistance systems, ADAS, have shown the possibility to
      anticipate crash accidents and effectively assist road users in critical traffic
      situations. This is not the case for motorcyclists, in fact ADAS for motorcycles
      are still barely developed. Our aim was to study a camera-based sensor for the
      application of preventive safety in tilting vehicles. We identified two road
      conflict situations for which automotive remote sensors installed in a tilting
      vehicle are likely to fail in the identification of critical obstacles.
      Accordingly, we set two experiments conducted in real traffic conditions to test
      our stereo vision sensor. Our promising results support the application of this
      type of sensors for advanced motorcycle safety applications.

PMID- 29351269
TI  - Bipolar or monopolar transurethral resection for benign prostatic hyperplasia?
AB  - INTRODUCTION: Transurethral resection is currently considered as standard
      endoscopic treatment for lower urinary tract obstruction due to benign
      hyperplasia under 80 cc. Monopolar resection loops has been traditionally used
      but bipolar energy has recently displaced precedent technology. The purpose of
      this summary is to evaluate the efficacy and safety of both technologies.
      METHODS: To answer this question we used Epistemonikos, the largest database of
      systematic reviews in health, which is maintained by screening multiple
      information sources, including MEDLINE, EMBASE, Cochrane, among others. We
      extracted data from the systematic reviews, reanalyzed data of primary studies,
      conducted a meta-analysis and generated a summary of findings table using the
      GRADE approach. RESULTS AND CONCLUSIONS: We identified 13 systematic reviews
      including 32 primary studies, among them 31 randomized trials. We concluded
      although there may be no difference in terms of efficacy among both techniques,
      the use of bipolar energy reduces the incidence of transurethral resection
      syndrome and probably reduces the risk of bleeding that requires red blood cell
      transfusion.

PMID- 29351268
TI  - Use of Different Methods of Intramedullary Nailing for Fixation of Distal Radius
      Fractures: A Retrospective Analysis of Clinical and Radiological Outcomes.
AB  - BACKGROUND We aimed to evaluate the clinical and radiologic outcomes of using
      Sonoma WRx versus Micronail intramedullary nailing for the fixation of distal
      radius fractures. MATERIAL AND METHODS A total of 68 patients with primarily
      extra-articular and simple intra-articular fractures of the distal radius who
      underwent intramedullary distal radius fixation using Sonoma WRx (n=39) or
      Micronail (n=29) intramedullary nails were enrolled in the study. The clinical
      outcome measures included the range of motion (ROM), visual analog scale (VAS),
      functional outcomes (patient-reported Disabilities of the Arm, Shoulder and Hand
      [DASH] score and clinician-based Gartland-Werley score), radiographic scores
      (Stewart score), and parameters related to the quality of radiographic reduction
      and complications (radial inclination, volar tilt, radial height, and radio-ulnar
      variance). RESULTS Significantly higher DASH (15.0+/-3.3 vs. 8.3+/-1.5, p<0.001)
      and Gartland-Werley (4.9+/-5.4 vs. 2.9+/-4.2, p=0.029) scores, longer scopy time
      (21.0+/-3.9 min vs. 15.8+/-2.5 min, p<0.001), lower ROM for wrist extension
      (69.5+/-4.4 degrees  vs. 77.1+/-7.6 degrees , p<0.001), higher ROM for wrist
      supination (81.9+/-5.1 degrees  vs. 78.7+/-3.1 degrees , p<0.001), and higher
      complications rates (37.9% vs. 15.4%, p=0.034) were noted in the Micronail group
      compared to those in the Sonoma WRx group. CONCLUSIONS Our findings revealed that
      Sonoma WRx and Micronail implants were equally effective and useful minimally
      invasive options for treating distal radius fractures. Further, we consider
      Sonoma WRx superior in terms of shorter operative time, lower complication rates,
      and better functional outcome scores.

PMID- 29351270
TI  - Is mytomicyn better than 5-fluorouracil as antimetabolite in trabeculectomy for
      glaucoma?
AB  - INTRODUCTION: Trabeculectomy is considered the standard for glaucoma surgery.
      Postoperative scarring is one the factors associated with surgery failure.
      Different antimetabolites have been used in order to reduce this risk,
      particularly 5-fluorouracil and mitomycin C. Although both are considered
      effective, it is not clear if they are different in terms of success of
      trabeculectomy and adverse effects. METHODS: To answer this question we used
      Epistemonikos, the largest database of systematic reviews in health, which is
      maintained by screening multiple information sources, including MEDLINE, EMBASE,
      Cochrane, among others. We extracted data from the systematic reviews, reanalyzed
      data of primary studies, conducted a meta-analysis and generated a summary of
      findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified
      four systematic reviews including 17 studies overall, of which 12 were randomized
      trials. We concluded mitomycin C might be more effective in reducing intraocular
      pressure and increasing qualified success compared to 5-fluorouracil. However,
      its use might be associated to a higher risk of complications.

PMID- 29351271
TI  - Risk factors for low birth weight according to the multiple logistic regression
      model. A retrospective cohort study in Jose Maria Morelos municipality, Quintana
      Roo, Mexico.
AB  - INTRODUCTION: Low birth weight has been an enigma for science over time. There
      have been many researches on its causes and its effects. Low birth weight is an
      indicator that predicts the probability of a child surviving. In fact, there is
      an exponential relationship between weight deficit, gestational age, and
      perinatal mortality. Multiple logistic regression is one of the most expressive
      and versatile statistical instruments available for the analysis of data in both
      clinical and epidemiology settings, as well as in public health. OBJECTIVE: To
      assess in a multivariate fashion the importance of 17 independent variables in
      low birth weight (dependent variable) of children born in the Mayan municipality
      of Jose Maria Morelos, Quintana Roo, Mexico. METHODS: Analytical observational
      epidemiological cohort study with retrospective temporality. Births that met the
      inclusion criteria occurred in the "Hospital Integral Jose Maria Morelos" of the
      Ministry of Health corresponding to the Maya municipality of Jose Maria Morelos
      during the period from August 1, 2014 to July 31, 2015. The total number of
      newborns recorded was 1,147; 84 of which (7.32%) had low birth weight. To
      estimate the independent association between the explanatory variables (potential
      risk factors) and the response variable, a multiple logistic regression analysis
      was performed using the IBM SPSS Statistics 22 software. RESULTS: In ascending
      numerical order values of odds ratio > 1 indicated the positive contribution of
      explanatory variables or possible risk factors: "unmarried" marital status
      (1.076, 95% confidence interval: 0.550 to 2.104); age at menarche <= 12 years
      (1.08, 95% confidence interval: 0.64 to 1.84); history of abortion(s) (1.14, 95%
      confidence interval: 0.44 to 2.93); maternal weight < 50 kg (1.51, 95% confidence
      interval: 0.83 to 2.76); number of prenatal consultations <= 5 (1.86, 95%
      confidence interval: 0.94 to 3.66); maternal age >= 36 years (3.5, 95% confidence
      interval: 0.40 to 30.47); maternal age <= 19 years (3.59, 95% confidence
      interval: 0.43 to 29.87); number of deliveries = 1 (3.86, 95% confidence
      interval: 0.33 to 44.85); personal pathological history (4.78, 95% confidence
      interval: 2.16 to 10.59); pathological obstetric history (5.01, 95% confidence
      interval: 1.66 to 15.18); maternal height < 150 cm (5.16, 95% confidence
      interval: 3.08 to 8.65); number of births >= 5 (5.99, 95% confidence interval:
      0.51 to 69.99); and smoking (15.63, 95% confidence interval: 1.07 to 227.97).
      CONCLUSIONS: Four of the independent variables (personal pathological history,
      obstetric pathological history, maternal stature <150 centimeters and smoking)
      showed a significant positive contribution, thus they can be considered as clear
      risk factors for low birth weight. The use of the logistic regression model in
      the Mayan municipality of Jose Maria Morelos, will allow estimating the
      probability of low birth weight for each pregnant woman in the future, which will
      be useful for the health authorities of the region.

PMID- 29351272
TI  - Current applications of multiparameter flow cytometry in plasma cell disorders.
AB  - This corrects the article DOI: 10.1038/bcj.2017.90.

PMID- 29351273
TI  - Understanding the legal trade of cattle and camels and the derived risk of Rift
      Valley Fever introduction into and transmission within Egypt.
AB  - Rift Valley Fever (RVF) is a mosquito-borne zoonosis, which may cause significant
      losses for the livestock sector and have serious public health implications.
      Egypt has been repeatedly affected by RVF epidemics, mainly associated to the
      importation of animals from sub-Saharan countries, where the disease is endemic.
      The objective of our study was the improvement of the surveillance and control
      strategies implemented in Egypt. In order to do that, first we evaluated the
      legal trade of live animals into and within Egypt. Then, we assessed the risk of
      Rift Valley Fever virus (RVFV) transmission within the country using a multi
      criteria evaluation approach. Finally, we combined the animal trade and the risk
      of RVFV transmission data to identify those areas and periods in which the
      introduction of RVFV is more likely. Our results indicate that the main risk of
      RVFV introduction is posed by the continuous flow of large number of camels
      coming from Sudan. The risk of RVFV transmission by vectors is restricted to the
      areas surrounding the Nile river, and does not vary significantly throughout the
      year. Imported camels are taken to quarantines, where the risk of RVFV
      transmission by vectors is generally low. Then, they are taken to animal markets
      or slaughterhouses, many located in populated areas, where the risk of RVFV
      transmission to animals or humans is much higher. The measures currently
      implemented (quarantines, vaccination or testing) seem to have a limited effect
      in reducing the risk of RVFV introduction, and therefore other (risk-based)
      surveillance strategies are proposed.

PMID- 29351274
TI  - DNA polymerase IV primarily operates outside of DNA replication forks in
      Escherichia coli.
AB  - In Escherichia coli, damage to the chromosomal DNA induces the SOS response,
      setting in motion a series of different DNA repair and damage tolerance pathways.
      DNA polymerase IV (pol IV) is one of three specialised DNA polymerases called
      into action during the SOS response to help cells tolerate certain types of DNA
      damage. The canonical view in the field is that pol IV primarily acts at
      replisomes that have stalled on the damaged DNA template. However, the results of
      several studies indicate that pol IV also acts on other substrates, including
      single-stranded DNA gaps left behind replisomes that re-initiate replication
      downstream of a lesion, stalled transcription complexes and recombination
      intermediates. In this study, we use single-molecule time-lapse microscopy to
      directly visualize fluorescently labelled pol IV in live cells. We treat cells
      with the DNA-damaging antibiotic ciprofloxacin, Methylmethane sulfonate (MMS) or
      ultraviolet light and measure changes in pol IV concentrations and cellular
      locations through time. We observe that only 5-10% of foci induced by DNA damage
      form close to replisomes, suggesting that pol IV predominantly carries out non
      replisomal functions. The minority of foci that do form close to replisomes
      exhibit a broad distribution of colocalisation distances, consistent with a
      significant proportion of pol IV molecules carrying out postreplicative TLS in
      gaps behind the replisome. Interestingly, the proportion of pol IV foci that form
      close to replisomes drops dramatically in the period 90-180 min after treatment,
      despite pol IV concentrations remaining relatively constant. In an SOS
      constitutive mutant that expresses high levels of pol IV, few foci are observed
      in the absence of damage, indicating that within cells access of pol IV to DNA is
      dependent on the presence of damage, as opposed to concentration-driven
      competition for binding sites.

PMID- 29351276
TI  - Static length changes of cochlear outer hair cells can tune low-frequency
      hearing.
AB  - The cochlea not only transduces sound-induced vibration into neural spikes, it
      also amplifies weak sound to boost its detection. Actuators of this active
      process are sensory outer hair cells in the organ of Corti, whereas the inner
      hair cells transduce the resulting motion into electric signals that propagate
      via the auditory nerve to the brain. However, how the outer hair cells modulate
      the stimulus to the inner hair cells remains unclear. Here, we combine
      theoretical modeling and experimental measurements near the cochlear apex to
      study the way in which length changes of the outer hair cells deform the organ of
      Corti. We develop a geometry-based kinematic model of the apical organ of Corti
      that reproduces salient, yet counter-intuitive features of the organ's motion.
      Our analysis further uncovers a mechanism by which a static length change of the
      outer hair cells can sensitively tune the signal transmitted to the sensory inner
      hair cells. When the outer hair cells are in an elongated state, stimulation of
      inner hair cells is largely inhibited, whereas outer hair cell contraction leads
      to a substantial enhancement of sound-evoked motion near the hair bundles. This
      novel mechanism for regulating the sensitivity of the hearing organ applies to
      the low frequencies that are most important for the perception of speech and
      music. We suggest that the proposed mechanism might underlie frequency
      discrimination at low auditory frequencies, as well as our ability to selectively
      attend auditory signals in noisy surroundings.

PMID- 29351277
TI  - Ex-ante assessment of different vaccination-based control schedules against the
      peste des petits ruminants virus in sub-Saharan Africa.
AB  - BACKGROUND: Peste des petits ruminants (PPR) is a highly contagious and
      widespread viral infection of small ruminants (goats and sheep), causing heavy
      economic losses in many developing countries. Therefore, its progressive control
      and global eradication by 2030 was defined as a priority by international
      organizations addressing animal health. The control phase of the global strategy
      is based on mass vaccination of small ruminant populations in endemic regions or
      countries. It is estimated that a 70% post-vaccination immunity rate (PVIR) is
      needed in a given epidemiological unit to prevent PPR virus spread. However,
      implementing mass vaccination is difficult and costly in smallholder farming
      systems with scattered livestock and limited facilities. Regarding this,
      controlling PPR is a special challenge in sub-Saharan Africa. In this study, we
      focused on this region to assess the effect of several variables of PVIR in two
      contrasted smallholder farming systems. METHODS: Using a seasonal matrix
      population model of PVIR, we estimated its decay in goats reared in sub-humid
      areas, and sheep reared in semi-arid areas, over a 4-year vaccination program.
      Assuming immunologically naive and PPR-free epidemiological unit, we assessed the
      ability of different vaccination scenarios to reach the 70% PVIR throughout the
      program. The tested scenarios differed in i) their overall schedule, ii) their
      delivery month and iii) their vaccination coverage. RESULTS: In sheep reared in
      semi-arid areas, the vaccination month did affect the PVIR decay though it did
      not in goats in humid regions. In both cases, our study highlighted i) the
      importance of targeting the whole eligible population at least during the two
      first years of the vaccination program and ii) the importance of reaching a
      vaccination coverage as high as 80% of this population. This study confirmed the
      relevance of the vaccination schedules recommended by international
      organizations.

PMID- 29351275
TI  - A mathematical model for IL-6-mediated, stem cell driven tumor growth and
      targeted treatment.
AB  - Targeting key regulators of the cancer stem cell phenotype to overcome their
      critical influence on tumor growth is a promising new strategy for cancer
      treatment. Here we present a modeling framework that operates at both the
      cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell
      driven tumor growth and targeted treatment with anti-IL6 antibodies. Our
      immediate goal is to quantify the influence of IL-6 on cancer stem cell self
      renewal and survival, and to characterize the subsequent impact on tumor growth
      dynamics. By including the molecular details of IL-6 binding, we are able to
      quantify the temporal changes in fractional occupancies of bound receptors and
      their influence on tumor volume. There is a strong correlation between the model
      output and experimental data for primary tumor xenografts. We also used the model
      to predict tumor response to administration of the humanized IL-6R monoclonal
      antibody, tocilizumab (TCZ), and we found that as little as 1mg/kg of TCZ
      administered weekly for 7 weeks is sufficient to result in tumor reduction and a
      sustained deceleration of tumor growth.

PMID- 29351278
TI  - Analysis of the tonsillar microbiome in young adults with sore throat reveals a
      high relative abundance of Fusobacterium necrophorum with low diversity.
AB  - Fusobacterium necrophorum (Fn), a gram-negative anaerobe, is increasingly
      implicated as an etiologic agent in older adolescents and young adults with sore
      throat. Inadequately treated Fn pharyngitis may result in suppurative
      complications such as peritonsillar abscess and Lemierre's syndrome. Data from
      the literature suggest that the incidence of life-threating complications in
      these age groups from Fn pharyngitis (Lemierre's syndrome) in the United States
      exceeds those associated with group A beta-hemolytic streptococcal (GAS)
      pharyngitis (acute rheumatic fever). Using real-time PCR, we previously reported
      about a 10% prevalence of Fn in asymptomatic medical students and about 20% in
      students complaining of sore throat at a university student health clinic (p =
      0.009). In this study, a comprehensive microbiome analysis of the same study
      samples confirms that Fn pharyngitis was more common than GAS pharyngitis.
      Eighteen patients were found to have Fn OTU values exceeding an arbitrary cutoff
      value of 0.1, i.e. greater than 10% of total sequences, with five subjects
      reaching values above 0.7. By contrast only 9 patients had GAS OTU values greater
      than 0.1 and none exceeded 0.6. When the data were analyzed using five separate
      assessments of alpha diversity, in each case for Fn there were statistically
      significant differences between Fn positive_high (OTU abundance > 0.1) vs
      control, Fn positive_high vs Fn negative (OTU abundance = 0), Fn positive_high vs
      Fn positive_low (OTU abundance > 0 and < 0.1). When the data were analyzed using
      three beta diversity indexes (Bray-Curtis, weighted unifrac, and unweighted
      unifrac), there were statistically significant differences between Fn
      positive_high (OTU abundance >= 0.1) vs control for all three. Statistically
      significant differences remained if we chose somewhat different OTU abundance
      cutoffs of 0.05 or 0.15. We conclude that Fn appears to play a dominant role in
      bacterial pharyngitis in the older adolescent and young adult age groups and that
      the development of a productive mucosal infection with Fn is linked to a
      significant decrease in the diversity of the associated tonsillar microbiome.

PMID- 29351279
TI  - Corrective binaural processing for bilateral cochlear implant patients.
AB  - Although bilateral cochlear implant users receive input to both ears, they
      nonetheless have relatively poor localization abilities in the horizontal plane.
      This is likely because of the two binaural cues, they have good sensitivity to
      interaural differences of level (inter-aural level differences, or ILDs), but not
      those of time (inter-aural time differences; ITDs). Here, localization
      performance is assessed in six bilateral cochlear implant patients when
      instantaneous ITDs are measured and converted to ILDs, a strategy that results in
      larger-than-typical ILDs. The added ILDs are corrective, in that they are derived
      from individual listener performance across both frequency and azimuth, so that
      they are small where a listener performs well, and increase as performance
      deviates from ideal. Results show significantly improved localization performance
      as a result of this strategy, with two of the six listeners achieving levels of
      performance typically observed in NH listeners.

PMID- 29351280
TI  - A generic framework for individual-based modelling and physical-biological
      interaction.
AB  - The increased availability of high-resolution ocean data globally has enabled
      more detailed analyses of physical-biological interactions and their consequences
      to the ecosystem. We present IBMlib, which is a versatile, portable and
      computationally effective framework for conducting Lagrangian simulations in the
      marine environment. The purpose of the framework is to handle complex individual
      level biological models of organisms, combined with realistic 3D oceanographic
      model of physics and biogeochemistry describing the environment of the organisms
      without assumptions about spatial or temporal scales. The open-source framework
      features a minimal robust interface to facilitate the coupling between individual
      level biological models and oceanographic models, and we provide application
      examples including forward/backward simulations, habitat connectivity
      calculations, assessing ocean conditions, comparison of physical circulation
      models, model ensemble runs and recently posterior Eulerian simulations using the
      IBMlib framework. We present the code design ideas behind the longevity of the
      code, our implementation experiences, as well as code performance benchmarking.
      The framework may contribute substantially to progresses in representing,
      understanding, predicting and eventually managing marine ecosystems.

PMID- 29351281
TI  - Automatic labeling of molecular biomarkers of immunohistochemistry images using
      fully convolutional networks.
AB  - This paper addresses the problem of quantifying biomarkers in multi-stained
      tissues based on the color and spatial information of microscopy images of the
      tissue. A deep learning-based method that can automatically localize and quantify
      the regions expressing biomarker(s) in any selected area on a whole slide image
      is proposed. The deep learning network, which we refer to as Whole Image (WI)
      Net, is a fully convolutional network whose input is the true RGB color image of
      a tissue and output is a map showing the locations of each biomarker. The WI-Net
      relies on a different network, Nuclei (N)-Net, which is a convolutional neural
      network that classifies each nucleus separately according to the biomarker(s) it
      expresses. In this study, images of immunohistochemistry (IHC)-stained slides
      were collected and used. Images of nuclei (4679 RGB images) were manually labeled
      based on the expressing biomarkers in each nucleus (as p16 positive, Ki-67
      positive, p16 and Ki-67 positive, p16 and Ki-67 negative). The labeled nuclei
      images were used to train the N-Net (obtaining an accuracy of 92% in a test set).
      The trained N-Net was then extended to WI-Net that generated a map of all
      biomarkers in any selected sub-image of the whole slide image acquired by the
      scanner (instead of classifying every nucleus image). The results of our method
      compare well with the manual labeling by humans (average F-score of 0.96). In
      addition, we carried a layer-based immunohistochemical analysis of cervical
      epithelium, and showed that our method can be used by pathologists to
      differentiate between different grades of cervical intraepithelial neoplasia by
      quantitatively assessing the percentage of proliferating cells in the different
      layers of HPV positive lesions.

PMID- 29351282
TI  - A four-component model of the action potential in mouse detrusor smooth muscle
      cell.
AB  - BACKGROUND AND HYPOTHESIS: Detrusor smooth muscle cells (DSMCs) of the urinary
      bladder are electrically connected to one another via gap junctions and form a
      three dimensional syncytium. DSMCs exhibit spontaneous electrical activity,
      including passive depolarizations and action potentials. The shapes of
      spontaneous action potentials (sAPs) observed from a single DSM cell can vary
      widely. The biophysical origins of this variability, and the precise components
      which contribute to the complex shapes observed are not known. To address these
      questions, the basic components which constitute the sAPs were investigated. We
      hypothesized that linear combinations of scaled versions of these basic
      components can produce sAP shapes observed in the syncytium. METHODS AND RESULTS:
      The basic components were identified as spontaneous evoked junction potentials
      (sEJP), native AP (nAP), slow after hyperpolarization (sAHP) and very slow after
      hyperpolarization (vsAHP). The experimental recordings were grouped into two
      sets: a training data set and a testing data set. A training set was used to
      estimate the components, and a test set to evaluate the efficiency of the
      estimated components. We found that a linear combination of the identified
      components when appropriately amplified and time shifted replicated various AP
      shapes to a high degree of similarity, as quantified by the root mean square
      error (RMSE) measure. CONCLUSIONS: We conclude that the four basic components
      sEJP, nAP, sAHP, and vsAHP-identified and isolated in this work are necessary and
      sufficient to replicate all varieties of the sAPs recorded experimentally in
      DSMCs. This model has the potential to generate testable hypotheses that can help
      identify the physiological processes underlying various features of the sAPs.
      Further, this model also provides a means to classify the sAPs into various shape
      classes.

PMID- 29351283
TI  - Decreased MiR-17 in glioma cells increased cell viability and migration by
      increasing the expression of Cyclin D1, p-Akt and Akt.
AB  - BACKGROUND: The activating mutations of micro RNA (miR)-17 have been revealed in
      tumors such as human non-Hodgkin's lymphoma and T cell leukemia. However, it is
      unclear about the role of miR-17 in glioma cells. The current study aimed to
      investigate effects of miR-17 mimics or inhibitor on the viability and migration
      of rat glioma C6 cells, and explore possible mechanisms. METHODS: The expression
      of miR-17 in rat glioma C6 cells and normal brain tissue was detected by
      quantitative PCR. Protein expression of Cyclin D1 in rat glioma C6 cells and
      normal brain tissue was measured by Western Blot. Glioma C6 cells were
      transfected with MiR-17 mimics or inhibitor. Cells that were not transfected
      (Lipofectamine only) and cells that were transfected with nonsense RNA negative
      control served as control. MTT assay was utilized to detect cell viability, and
      cell wound scratch assay was utilized to examine the migration index. In
      addition, protein expression of Cyclin D1, p-Akt and Akt in MiR-17 mimics or
      inhibitor-transfected glioma C6 cells was detected by Western Blot. This study
      had been approved by the Medical Ethics Committee of the First Affiliated
      Hospital of Soochow University. All applicable international, national, and/or
      institutional guidelines for the care and use of animals were followed. RESULTS:
      The expression of miR-17 was significantly lower, whereas the expression of
      Cyclin D1 was significantly higher in glioma C6 cells compared to normal brain
      tissue. MiR-17 mimics decreased the viability and migration of glioma C6 cells
      markedly at 48 h. In addition, MiR-17 inhibitor increased the viability and
      migration of glioma C6 cells at 24 and 48 h. The protein expression of Cyclin D1,
      p-Akt and Akt in glioma C6 cells decreased after transfection with miR-17 mimics
      for 72 h, and increased after transfection with miR-17 inhibitor for 72 h.
      CONCLUSIONS: The reduced miR-17 levels in glioma cells increased cell viability
      and migration, which correlates with increased expression of Cyclin D1, p-Akt and
      Akt.

PMID- 29351284
TI  - Magnetic resonance angiography with compressed sensing: An evaluation of moyamoya
      disease.
AB  - Compressed sensing (CS) reconstructions of under-sampled measurements generate
      missing data based on assumptions of image sparsity. Non-contrast time-of-flight
      MR angiography (TOF-MRA) is a good candidate for CS based acceleration, as MRA
      images feature bright trees of sparse vessels over a well-suppressed anatomical
      background signal. A short scan time derived from CS is beneficial for patients
      of moyamoya disease (MMD) because of the frequency of MR scans. The purpose of
      this study was to investigate the reliability of TOF-MRA with CS in the
      evaluation of MMD. Twenty-two patients were examined using TOF-MRA with CS (CS
      TOF) and parallel imaging (PI-TOF). The acceleration factors were 3 (CS3) and 5
      (CS5) for CS-TOF, and 3 (PI3) for PI-TOF. Two neuroradiologists evaluated the MMD
      grading according to stenosis/occlusion scores using the modified Houkin's
      system, and the visibility of moyamoya vessels (MMVs) using a 3-point scale.
      Concordance was calculated with Cohen's kappa. The numbers of MMVs in the basal
      ganglia were compared using Bland-Altman analysis and Wilcoxon's signed-rank
      tests. MRA scan times were 4:07, 3:53, and 2:42 for PI3, CS3, and CS5,
      respectively. CS-reconstruction completed within 10 minutes. MMD grading and MMV
      visibility scales showed excellent correlation (kappa > .966). Although the
      number of MMVs was significantly higher in CS3 than in PI3 (p < .0001) and CS5 (p
      < .0001), Bland-Altman analysis showed a good agreement between PI3, CS3, and
      CS5. Compressed sensing can accelerate TOF-MRA with improved visualization of
      small collaterals in equivalent time (CS3) or equivalent results in a shorter
      scan time (CS5).

PMID- 29351285
TI  - Wine yeast phenomics: A standardized fermentation method for assessing
      quantitative traits of Saccharomyces cerevisiae strains in enological conditions.
AB  - This work describes the set up of a small scale fermentation methodology for
      measuring quantitative traits of hundreds of samples in an enological context. By
      using standardized screw cap vessels, the alcoholic fermentation kinetics of
      Saccharomyces cerevisiae strains were measured by following their weight loss
      over the time. This dispositive was coupled with robotized enzymatic assays for
      measuring metabolites of enological interest in natural grape juices. Despite the
      small volume used, kinetic parameters and fermentation end products measured are
      similar with those observed in larger scale vats. The vessel used also offers the
      possibility to assay 32 volatiles compounds using a headspace solid-phase micro
      extraction coupled to gas chromatography and mass spectrometry. The vessel
      shaking applied strongly impacted most of the phenotypes investigated due to
      oxygen transfer occuring in the first hours of the alcoholic fermentation. The
      impact of grape must and micro-oxygenation was investigated illustrating some
      relevant genetic x environmental interactions. By phenotyping a wide panel of
      commercial wine starters in five grape juices, broad phenotypic correlations
      between kinetics and metabolic end products were evidentiated. Moreover, a
      multivariate analysis illustrates that some grape musts are more able than others
      to discriminate commercial strains since some are less robust to environmental
      changes.

PMID- 29351287
TI  - A novel association rule mining approach using TID intermediate itemset.
AB  - Designing an efficient association rule mining (ARM) algorithm for multilevel
      knowledge-based transactional databases that is appropriate for real-world
      deployments is of paramount concern. However, dynamic decision making that needs
      to modify the threshold either to minimize or maximize the output knowledge
      certainly necessitates the extant state-of-the-art algorithms to rescan the
      entire database. Subsequently, the process incurs heavy computation cost and is
      not feasible for real-time applications. The paper addresses efficiently the
      problem of threshold dynamic updation for a given purpose. The paper contributes
      by presenting a novel ARM approach that creates an intermediate itemset and
      applies a threshold to extract categorical frequent itemsets with diverse
      threshold values. Thus, improving the overall efficiency as we no longer needs to
      scan the whole database. After the entire itemset is built, we are able to obtain
      real support without the need of rebuilding the itemset (e.g. Itemset list is
      intersected to obtain the actual support). Moreover, the algorithm supports to
      extract many frequent itemsets according to a pre-determined minimum support with
      an independent purpose. Additionally, the experimental results of our proposed
      approach demonstrate the capability to be deployed in any mining system in a
      fully parallel mode; consequently, increasing the efficiency of the real-time
      association rules discovery process. The proposed approach outperforms the extant
      state-of-the-art and shows promising results that reduce computation cost,
      increase accuracy, and produce all possible itemsets.

PMID- 29351286
TI  - Socio-economic determinants of physical activity across the life course: A
      "DEterminants of DIet and Physical ACtivity" (DEDIPAC) umbrella literature
      review.
AB  - BACKGROUND: To date, the scientific literature on socioeconomic correlates and
      determinants of physical activity behaviours has been dispersed throughout a
      number of systematic reviews, often focusing on one factor (e.g. education or
      parental income) in one specific age group (e.g. pre-school children or adults).
      The aim of this umbrella review is to provide a comprehensive and systematic
      overview of the scientific literature from previously conducted research by
      summarising and synthesising the importance and strength of the evidence related
      to socioeconomic correlates and determinants of PA behaviours across the life
      course. METHODS: Medline, Embase, ISI Web of Science, Scopus and SPORTDiscus were
      searched for systematic literature reviews and meta-analyses of observational
      studies investigating the association between socioeconomic determinants of PA
      and PA itself (from January 2004 to September 2017). Data extraction evaluated
      the importance of determinants, strength of evidence, and methodological quality
      of the selected papers. The full protocol is available from PROSPERO
      (PROSPERO2014:CRD42015010616). RESULTS: Nineteen reviews were included. Moderate
      methodological quality emerged. For adults, convincing evidence supports a
      relationship between PA and socioeconomic status (SES), especially in relation to
      leisure time (positive relationship) and occupational PA (negative relationship).
      Conversely, no association between PA and SES or parental SES was found for pre
      school, school-aged children and adolescents. CONCLUSIONS: Available evidence on
      the socioeconomic determinants of PA behaviour across the life course is probable
      (shows fairly consistent associations) at best. While some evidence is available
      for adults, less was available for youth. This is mainly due to a limited
      quantity of primary studies, weak research designs and lack of accuracy in the PA
      and SES assessment methods employed. Further PA domain specific studies using
      longitudinal design and clear measures of SES and PA assessment are required.

PMID- 29351289
TI  - The rumour spectrum.
AB  - Rumour is an old social phenomenon used in politics and other public spaces. It
      has been studied for only hundred years by sociologists and psychologists by
      qualitative means. Social media platforms open new opportunities to improve
      quantitative analyses. We scanned all scientific literature to find relevant
      features. We made a quantitative screening of some specific rumours (in French
      and in English). Firstly, we identified some sources of information to find them.
      Secondly, we compiled different reference, rumouring and event datasets. Thirdly,
      we considered two facets of a rumour: the way it can spread to other users, and
      the syntagmatic content that may or may not be specific for a rumour. We found 53
      features, clustered into six categories, which are able to describe a rumour
      message. The spread of a rumour is multi-harmonic having different frequencies
      and spikes, and can survive several years. Combinations of words (n-grams and
      skip-grams) are not typical of expressivity between rumours and news but study of
      lexical transition from a time period to the next goes in the sense of
      transmission pattern as described by Allport theory of transmission. A rumour can
      be interpreted as a speech act but with transmission patterns.

PMID- 29351290
TI  - Land-use change in oil palm dominated tropical landscapes-An agent-based model to
      explore ecological and socio-economic trade-offs.
AB  - Land-use changes have dramatically transformed tropical landscapes. We describe
      an ecological-economic land-use change model as an integrated, exploratory tool
      used to analyze how tropical land-use change affects ecological and socio
      economic functions. The model analysis seeks to determine what kind of landscape
      mosaic can improve the ensemble of ecosystem functioning, biodiversity, and
      economic benefit based on the synergies and trade-offs that we have to account
      for. More specifically, (1) how do specific ecosystem functions, such as carbon
      storage, and economic functions, such as household consumption, relate to each
      other? (2) How do external factors, such as the output prices of crops, affect
      these relationships? (3) How do these relationships change when production
      inefficiency differs between smallholder farmers and learning is incorporated? We
      initialize the ecological-economic model with artificially generated land-use
      maps parameterized to our study region. The economic sub-model simulates
      smallholder land-use management decisions based on a profit maximization
      assumption. Each household determines factor inputs for all household fields and
      decides on land-use change based on available wealth. The ecological sub-model
      includes a simple account of carbon sequestration in above-ground and below
      ground vegetation. We demonstrate model capabilities with results on household
      consumption and carbon sequestration from different output price and farming
      efficiency scenarios. The overall results reveal complex interactions between the
      economic and ecological spheres. For instance, model scenarios with heterogeneous
      crop-specific household productivity reveal a comparatively high inertia of land
      use change. Our model analysis even shows such an increased temporal stability in
      landscape composition and carbon stocks of the agricultural area under dynamic
      price trends. These findings underline the utility of ecological-economic models,
      such as ours, to act as exploratory tools which can advance our understanding of
      the mechanisms underlying the trade-offs and synergies of ecological and economic
      functions in tropical landscapes.

PMID- 29351288
TI  - Environmental enteric dysfunction pathways and child stunting: A systematic
      review.
AB  - BACKGROUND: Environmental enteric dysfunction (EED) is commonly defined as an
      acquired subclinical disorder of the small intestine, characterized by villous
      atrophy and crypt hyperplasia. EED has been proposed to underlie stunted growth
      among children in developing countries. A collection of biomarkers, organized
      into distinct domains, has been used to measure different aspects of EED. Here,
      we examine whether these hypothesized relationships, among EED domains and
      between each domain and stunting, are supported by data from recent studies.
      METHODOLOGY: A systematic literature search was conducted using PubMed, MEDLINE,
      EMBASE, Web of Science, and CINAHL between January 1, 2010 and April 20, 2017.
      Information on study objective, design, population, location, biomarkers, and
      results were recorded, as well as qualitative and quantitative definitions of
      EED. Biomarkers were organized into five EED domains, and the number of studies
      that support or do not support relationships among domains and between each
      domain with stunting were summarized. RESULTS: There was little evidence to
      support the pathway from intestinal permeability to microbial translocation and
      from microbial translocation to stunting, but stronger support existed for the
      link between intestinal inflammation and systemic inflammation and for intestinal
      inflammation and stunting. There was conflicting evidence for the pathways from
      intestinal damage to intestinal permeability and intestinal damage to stunting.
      CONCLUSIONS: These results suggest that certain EED biomarkers may require
      reconsideration, particularly those most difficult to measure, such as microbial
      translocation and intestinal permeability. We discuss several issues with
      currently used biomarkers and recommend further analysis of pathogen-induced
      changes to the intestinal microbiota as a pathway leading to stunting.

PMID- 29351291
TI  - Allometric biomass equations for 12 tree species in coniferous and broadleaved
      mixed forests, Northeastern China.
AB  - Understanding forest carbon budget and dynamics for sustainable resource
      management and ecosystem functions requires quantification of above- and below
      ground biomass at individual tree species and stand levels. In this study, a
      total of 122 trees (9-12 per species) were destructively sampled to determine
      above- and below-ground biomass of 12 tree species (Acer mandshuricum, Acer mono,
      Betula platyphylla, Carpinus cordata, Fraxinus mandshurica, Juglans mandshurica,
      Maackia amurensis, P. koraiensis, Populus ussuriensis, Quercus mongolica, Tilia
      amurensis and Ulmus japonica) in coniferous and broadleaved mixed forests of
      Northeastern China, an area of the largest natural forest in the country. Biomass
      allocation was examined and biomass models were developed using diameter as
      independent variable for individual tree species and all species combined. The
      results showed that the largest biomass allocation of all species combined was on
      stems (57.1%), followed by coarse root (21.3%), branch (18.7%), and foliage
      (2.9%). The log-transformed model was statistically significant for all biomass
      components, although predicting power was higher for species-specific models than
      for all species combined, general biomass models, and higher for stems, roots,
      above-ground biomass, and total tree biomass than for branch and foliage biomass.
      These findings supplement the previous studies on this forest type by additional
      sample trees, species and locations, and support biomass research on forest
      carbon budget and dynamics by management activities such as thinning and
      harvesting in the northeastern part of China.

PMID- 29351293
TI  - Fibroblast growth factor receptor 1 amplification in laryngeal squamous cell
      carcinoma.
AB  - Fibroblast growth factor receptor 1 (FGFR1) has been noted to be amplified in a
      variety of squamous cell carcinomas (SCCa) of the head, neck, and lung and
      increased copy number (CN) is a predictor of poor outcomes. FGFR1 is a
      therapeutic target for lung SCCa and inhibition therapy is currently in clinical
      trials. Absolute quantification of FGFR1 from formalin fixed paraffin embedded
      (FFPE) tissue of laryngeal SCCa was examined in this retrospective study. A
      droplet digital polymerase chain reaction (ddPCR) was used for absolute
      quantitation of the FGFR1 gene CN. Of the 74 samples analyzed, FGFR1 CN analysis
      revealed 54% of samples had CN greater than 2 copies/cell (1.8-2.2 copies/cell),
      and 38% had CN values greater than 3. The mean and standard deviation FGFR1 CN
      was 4.17 +/- 1.46 CN for African American patients (n = 41) and 3.78 +/-1.85 CN
      for Caucasian patients (n = 31). Further, 60.9% of specimens from African
      Americans demonstrated increased FGFR1 CN compared to 48.4% of Caucasians. Two
      SCCA samples from Native American demonstrated increased FGFR1 CN (4.19 and 3.01
      CN). The level of FGFR1 amplification did not correlate with tumor stage, lymph
      node staging, or metastasis. In this population, the proportion of patient
      samples with an FGFR1 amplification was three times higher than in reported for
      SCCA of the head and neck. Further, increased FGFR1 CN was observed in two racial
      groups not previously reported: African Americans and Native Americans. However,
      FGFR1 amplification is not prognostic in laryngeal squamous cell carcinomas.

PMID- 29351292
TI  - Allocation of distinct organ fates from a precursor field requires a shift in
      expression and function of gene regulatory networks.
AB  - A common occurrence in metazoan development is the rise of multiple
      tissues/organs from a single uniform precursor field. One example is the anterior
      forebrain of vertebrates, which produces the eyes, hypothalamus, diencephalon,
      and telencephalon. Another instance is the Drosophila wing disc, which generates
      the adult wing blade, the hinge, and the thorax. Gene regulatory networks (GRNs)
      that are comprised of signaling pathways and batteries of transcription factors
      parcel the undifferentiated field into discrete territories. This simple model is
      challenged by two observations. First, many GRN members that are thought to
      control the fate of one organ are actually expressed throughout the entire
      precursor field at earlier points in development. Second, each GRN can
      simultaneously promote one of the possible fates choices while repressing the
      other alternatives. It is therefore unclear how GRNs function to allocate tissue
      fates if their members are uniformly expressed and competing with each other
      within the same populations of cells. We address this paradigm by studying fate
      specification in the Drosophila eye-antennal disc. The disc, which begins its
      development as a homogeneous precursor field, produces a number of adult
      structures including the compound eyes, the ocelli, the antennae, the maxillary
      palps, and the surrounding head epidermis. Several selector genes that control
      the fates of the eye and antenna, respectively, are first expressed throughout
      the entire eye-antennal disc. We show that during early stages, these genes are
      tasked with promoting the growth of the entire field. Upon segregation to
      distinct territories within the disc, each GRN continues to promote growth while
      taking on the additional roles of promoting distinct primary fates and repressing
      alternate fates. The timing of both expression pattern restriction and expansion
      of functional duties is an elemental requirement for allocating fates within a
      single field.

PMID- 29351294
TI  - A HAD family phosphatase CSP-6 regulates the circadian output pathway in
      Neurospora crassa.
AB  - Circadian clocks are ubiquitous in eukaryotic organisms where they are used to
      anticipate regularly occurring diurnal and seasonal environmental changes.
      Nevertheless, little is known regarding pathways connecting the core clock to its
      output pathways. Here, we report that the HAD family phosphatase CSP-6 is
      required for overt circadian clock output but not for the core oscillation. The
      loss of function Deltacsp-6 deletion mutant is overtly arrhythmic on race tubes
      under free running conditions; however, reporter assays confirm that the
      FREQUENCY-WHITE COLLAR COMPLEX core circadian oscillator is functional,
      indicating a discrete block between oscillator and output. CSP-6 physically
      interacts with WHI-2, Deltawhi-2 mutant phenotypes resemble Deltacsp-6, and the
      CSP-6/WHI-2 complex physically interacts with WC-1, all suggesting that WC-1 is a
      direct target for CSP-6/WHI-2-mediated dephosphorylation and consistent with
      observed WC-1 hyperphosphorylation in Deltacsp-6. To identify the source of the
      block to output, known clock-controlled transcription factors were screened for
      rhythmicity in Deltacsp-6, identifying loss of circadian control of ADV-1, a
      direct target of WC-1, as responsible for the loss of overt rhythmicity. The CSP
      6/WHI-2 complex thus participates in the clock output pathway by regulating WC-1
      phosphorylation to promote proper transcriptional/translational activation of adv
      1/ADV-1; these data establish an unexpected essential role for post-translational
      modification parallel to circadian transcriptional regulation in the early steps
      of circadian output.

PMID- 29351295
TI  - Effects of a population-based, person-centred and integrated care service on
      health, wellbeing and self-management of community-living older adults: A
      randomised controlled trial on Embrace.
AB  - OBJECTIVE: To evaluate the effects of the population-based, person-centred and
      integrated care service 'Embrace' at twelve months on three domains comprising
      health, wellbeing and self-management among community-living older people.
      METHODS: Embrace supports older adults to age in place. A multidisciplinary team
      provides care and support, with intensity depending on the older adults' risk
      profile. A randomised controlled trial was conducted in fifteen general practices
      in the Netherlands. Older adults (>=75 years) were included and stratified into
      three risk profiles: Robust, Frail and Complex care needs, and randomised to
      Embrace or care as usual (CAU). Outcomes were recorded in three domains. The
      EuroQol-5D-3L and visual analogue scale, INTERMED for the Elderly Self
      Assessment, Groningen Frailty Indicator and Katz-15 were used for the domain
      'Health.' The Groningen Well-being Indicator and two quality of life questions
      measured 'Wellbeing.' The Self-Management Ability Scale and Partners in Health
      scale for older adults (PIH-OA) were used for 'Self-management.' Primary and
      secondary outcome measurements differed per risk profile. Data were analysed with
      multilevel mixed-model techniques using intention-to-treat and complete case
      analyses, for the whole sample and per risk profile. RESULTS: 1456 eligible older
      adults participated (49%) and were randomized to Embrace (n(T0) = 747, n(T1) =
      570, mean age 80.6 years (SD 4.5), 54.2% female) and CAU (n(T0) = 709, n(T1) =
      561, mean age 80.8 years (SD 4.7), 55.6% female). Embrace participants showed a
      greater-but clinically irrelevant-improvement in self-management (PIH-OA
      Knowledge subscale effect size [ES] = 0.14), and a greater-but clinically
      relevant-deterioration in health (ADL ES = 0.10; physical ADL ES = 0.13) compared
      to CAU. No differences in change in wellbeing were observed. This picture was
      also found in the risk profiles. Complete case analyses showed comparable
      results. CONCLUSIONS: This study found no clear benefits to receiving person
      centred and integrated care for twelve months for the domains of health,
      wellbeing and self-management in community-living older adults.

PMID- 29351297
TI  - A fast combination method in DSmT and its application to recommender system.
AB  - In many applications involving epistemic uncertainties usually modeled by belief
      functions, it is often necessary to approximate general (non-Bayesian) basic
      belief assignments (BBAs) to subjective probabilities (called Bayesian BBAs).
      This necessity occurs if one needs to embed the fusion result in a system based
      on the probabilistic framework and Bayesian inference (e.g. tracking systems), or
      if one needs to make a decision in the decision making problems. In this paper,
      we present a new fast combination method, called modified rigid coarsening (MRC),
      to obtain the final Bayesian BBAs based on hierarchical decomposition
      (coarsening) of the frame of discernment. Regarding this method, focal elements
      with probabilities are coarsened efficiently to reduce computational complexity
      in the process of combination by using disagreement vector and a simple
      dichotomous approach. In order to prove the practicality of our approach, this
      new approach is applied to combine users' soft preferences in recommender systems
      (RSs). Additionally, in order to make a comprehensive performance comparison, the
      proportional conflict redistribution rule #6 (PCR6) is regarded as a baseline in
      a range of experiments. According to the results of experiments, MRC is more
      effective in accuracy of recommendations compared to original Rigid Coarsening
      (RC) method and comparable in computational time.

PMID- 29351296
TI  - Hybrid genome assembly and annotation of Paenibacillus pasadenensis strain R16
      reveals insights on endophytic life style and antifungal activity.
AB  - Bacteria of the Paenibacillus genus are becoming important in many fields of
      science, including agriculture, for their positive effects on the health of
      plants. However, there are little information available on this genus compared to
      other bacteria (such as Bacillus or Pseudomonas), especially when considering
      genomic information. Sequencing the genomes of plant-beneficial bacteria is a
      crucial step to identify the genetic elements underlying the adaptation to life
      inside a plant host and, in particular, which of these features determine the
      differences between a helpful microorganism and a pathogenic one. In this study,
      we have characterized the genome of Paenibacillus pasadenensis, strain R16,
      recently investigated for its antifungal activities and plant-associated
      features. An hybrid assembly approach was used integrating the very precise reads
      obtained by Illumina technology and long fragments acquired with Oxford Nanopore
      Technology (ONT) sequencing. De novo genome assembly based solely on Illumina
      reads generated a relatively fragmented assembly of 5.72 Mbp in 99 ungapped
      sequences with an N50 length of 544 Kbp; hybrid assembly, integrating Illumina
      and ONT reads, improved the assembly quality, generating a genome of 5.75 Mbp,
      organized in 6 contigs with an N50 length of 3.4 Mbp. Annotation of the latter
      genome identified 4987 coding sequences, of which 1610 are hypothetical proteins.
      Enrichment analysis identified pathways of particular interest for the endophyte
      biology, including the chitin-utilization pathway and the incomplete siderophore
      pathway which hints at siderophore parasitism. In addition the analysis led to
      the identification of genes for the production of terpenes, as for example
      farnesol, that was hypothesized as the main antifungal molecule produced by the
      strain. The functional analysis on the genome confirmed several plant-associated,
      plant-growth promotion, and biocontrol traits of strain R16, thus adding insights
      in the genetic bases of these complex features, and of the Paenibacillus genus in
      general.

PMID- 29351298
TI  - Construction of an infectious horsepox virus vaccine from chemically synthesized
      DNA fragments.
AB  - Edward Jenner and his contemporaries believed that his variolae vaccinae
      originated in horses and molecular analyses show that modern vaccinia virus
      (VACV) strains share common ancestry with horsepox virus (HPXV). Given concerns
      relating to the toxicity of modern VACV vaccines, we asked whether an HPXV-based
      vaccine might provide a superior alternative. Since HPXV may be extinct and the
      only specimen of HPXV that has been identified is unavailable for investigation,
      we explored whether HPXV could be obtained by large-scale gene synthesis. Ten
      large (10-30 kb) fragments of DNA were synthesized based on the HPXV sequence
      along with two 157 nt VACV terminal sequences, and were recombined into a live
      synthetic chimeric HPXV (scHPXV) in cells infected with Shope fibroma virus
      (SFV). Sequencing of the 212 kbp scHPXV confirmed it encoded a faithful copy of
      the input DNA. We believe this is the first complete synthesis of a poxvirus
      using synthetic biology approaches. This scHPXV produced smaller plaques,
      produced less extracellular virus and exhibited less virulence in mice than VACV,
      but still provided vaccine protection against a lethal VACV challenge.
      Collectively, these findings support further development of scHPXV as a novel
      replication-proficient smallpox vaccine.

PMID- 29351299
TI  - What influences where they seek care? Caregivers' preferences for under-five
      child healthcare services in urban slums of Malawi: A discrete choice experiment.
AB  - Access to and utilisation of quality healthcare promotes positive child health
      outcomes. However, to be optimally utilised, the healthcare system needs to be
      responsive to the expectations of the population it serves. Health systems in
      many sub-Saharan African countries, including Malawi, have historically focused
      on promoting access to health services by the rural poor. However, in the context
      of increasing urbanisation and consequent proliferation of urban slums, promoting
      health of children under five years of age in these settings is a public health
      imperative. We conducted a discrete choice experiment to determine the relative
      importance of health facility factors in seeking healthcare for childhood
      illnesses in urban slums of Malawi. Caregivers of children under five years of
      age were presented with choice cards that depicted two hypothetical health
      facilities using six health facility attributes: availability of medicines and
      supplies, thoroughness of physical examination of the child, attitude of health
      workers, cost, distance, and waiting time. Caregivers were asked to indicate the
      health facility they would prefer to use. A mixed logit model was used to
      estimate the relative importance of and willingness to pay (WTP) for health
      facility attributes. Attributes with greatest influence on choice were:
      availability of medicines and supplies (beta = 0.842, p<0.001) and thorough
      examination of the child (beta = 0.479, p <0.001) with WTP of MK3698.32 ($11)
      (95% CI: $8-$13) and MK2049.13 ($6) (95% CI: $3-$9) respectively. Respondents
      were willing to pay 1.8 and 2.4 times more for medicine availability over
      thorough examination and positive attitude of health workers respectively.
      Therefore, strengthening health service delivery system through investment in
      sustained availability of essential medicines and supplies, sufficient and
      competent health workforce with positive attitude and clinical discipline to
      undertake thorough examination, and reductions in waiting times have the
      potential to improve child healthcare utilization in the urban slums.

PMID- 29351300
TI  - Empirical validation of an agent-based model of wood markets in Switzerland.
AB  - We present an agent-based model of wood markets and show our efforts to validate
      this model using empirical data from different sources, including interviews,
      workshops, experiments, and official statistics. Own surveys closed gaps where
      data was not available. Our approach to model validation used a variety of
      techniques, including the replication of historical production amounts, prices,
      and survey results, as well as a historical case study of a large sawmill
      entering the market and becoming insolvent only a few years later. Validating the
      model using this case provided additional insights, showing how the model can be
      used to simulate scenarios of resource availability and resource allocation. We
      conclude that the outcome of the rigorous validation qualifies the model to
      simulate scenarios concerning resource availability and allocation in our study
      region.

PMID- 29351301
TI  - Investigation of the proton relay system operative in human cystosolic
      aminopeptidase P.
AB  - Aminopeptidase P, a metalloprotease, targets Xaa-Proline peptides for cleavage [1
      4]. There are two forms of human AMPP, a membrane-bound form (hmAMPP) and a
      soluble cytosolic form (hcAMPP)[5]. Similar to the angiotensin-I-converting
      enzyme, AMPP plays an important role in the catabolism of inflammatory and
      vasoactive peptides, known as kinins. The plasma kinin, bradykinin, was used as
      the substrate to conduct enzymatic activity analyses and to determine the
      Michaelis constant (Km) of 174 MUM and the catalytic rate constant (kcat) of 10.8
      s-1 for hcAMPP. Significant differences were observed in the activities of Y527F
      and R535A hcAMPP mutants, which displayed a 6-fold and 13.5-fold for decrease in
      turnover rate, respectively. Guanidine hydrochloride restored the activity of
      R535A hcAMPP, increasing the kcat/Km 20-fold, yet it had no impact on the
      activities of the wild-type or Y527F mutant hcAMPPs. Activity restoration by
      guanidine derivatives followed the order guanidine hydrochloride >> methyl
      guanidine > amino-guanidine > N-ethyl-guanidine. Overall, the results indicate
      the participation of R535 in the hydrogen bond network that forms a proton relay
      system. The quaternary structure of hcAMPP was determined by using analytical
      ultracentrifugation (AUC). The results show that alanine replacement of Arg535
      destabilizes the hcAMPP dimer and that guanidine hydrochloride restores the
      native monomer-dimer equilibrium. It is proposed that Arg535 plays an important
      role in hcAMMP catalysis and in stabilization of the catalytically active dimeric
      state.

PMID- 29351302
TI  - Extension of the viral ecology in humans using viral profile hidden Markov
      models.
AB  - When human samples are sequenced, many assembled contigs are "unknown", as
      conventional alignments find no similarity to known sequences. Hidden Markov
      models (HMM) exploit the positions of specific nucleotides in protein-encoding
      codons in various microbes. The algorithm HMMER3 implements HMM using a reference
      set of sequences encoding viral proteins, "vFam". We used HMMER3 analysis of
      "unknown" human sample-derived sequences and identified 510 contigs distantly
      related to viruses (Anelloviridae (n = 1), Baculoviridae (n = 34), Circoviridae
      (n = 35), Caulimoviridae (n = 3), Closteroviridae (n = 5), Geminiviridae (n =
      21), Herpesviridae (n = 10), Iridoviridae (n = 12), Marseillevirus (n = 26),
      Mimiviridae (n = 80), Phycodnaviridae (n = 165), Poxviridae (n = 23),
      Retroviridae (n = 6) and 89 contigs related to described viruses not yet assigned
      to any taxonomic family). In summary, we find that analysis using the HMMER3
      algorithm and the "vFam" database greatly extended the detection of viruses in
      biospecimens from humans.

PMID- 29351303
TI  - Automated inverse optimization facilitates lower doses to normal tissue in
      pancreatic stereotactic body radiotherapy.
AB  - PURPOSE: Inverse planning is trial-and-error iterative process. This work
      introduces a fully automated inverse optimization approach, where the treatment
      plan is closely tailored to the unique patient anatomy. The auto-optimization is
      applied to pancreatic stereotactic body radiotherapy (SBRT). MATERIALS AND
      METHODS: The automation is based on stepwise reduction of dose-volume histograms
      (DVHs). Five uniformly spaced points, from 1% to 70% of the organ at risk (OAR)
      volumes, are used. Doses to those DVH points are iteratively decreased through
      multiple optimization runs. With each optimization run the doses to the OARs are
      decreased, while the dose homogeneity over the target is increased. The iterative
      process is terminated when a pre-specified dose heterogeneity over the target is
      reached. Twelve pancreatic cases were retrospectively studied. Doses to the
      target, maximum doses to duodenum, bowel, stomach, and spinal cord were
      evaluated. In addition, mean doses to liver and kidneys were tallied. The auto
      optimized plans were compared to the actual treatment plans, which are based on
      national protocols. RESULTS: The prescription dose to 95% of the planning target
      volume (PTV) is the same for the treatment and the auto-optimized plans. The
      average difference for maximum doses to duodenum, bowel, stomach, and spinal cord
      are -4.6 Gy, -1.8 Gy, -1.6 Gy, and -2.4 Gy respectively. The negative sign
      indicates lower doses with the auto-optimization. The average differences in the
      mean doses to liver and kidneys are -0.6 Gy, and -1.1 Gy to -1.5 Gy respectively.
      CONCLUSIONS: Automated inverse optimization holds great potential for
      personalization and tailoring of radiotherapy to particular patient anatomies. It
      can be utilized for normal tissue sparing or for an isotoxic dose escalation.

PMID- 29351304
TI  - Evolutionary algorithm based heuristic scheme for nonlinear heat transfer
      equations.
AB  - In this paper, a hybrid heuristic scheme based on two different basis functions
      i.e. Log Sigmoid and Bernstein Polynomial with unknown parameters is used for
      solving the nonlinear heat transfer equations efficiently. The proposed technique
      transforms the given nonlinear ordinary differential equation into an equivalent
      global error minimization problem. Trial solution for the given nonlinear
      differential equation is formulated using a fitness function with unknown
      parameters. The proposed hybrid scheme of Genetic Algorithm (GA) with Interior
      Point Algorithm (IPA) is opted to solve the minimization problem and to achieve
      the optimal values of unknown parameters. The effectiveness of the proposed
      scheme is validated by solving nonlinear heat transfer equations. The results
      obtained by the proposed scheme are compared and found in sharp agreement with
      both the exact solution and solution obtained by Haar Wavelet-Quasilinearization
      technique which witnesses the effectiveness and viability of the suggested
      scheme. Moreover, the statistical analysis is also conducted for investigating
      the stability and reliability of the presented scheme.

PMID- 29351305
TI  - Gender stereotypes and education: A comparative content analysis of Malaysian,
      Indonesian, Pakistani and Bangladeshi school textbooks.
AB  - Using government secondary school English language textbooks from Malaysia,
      Indonesia, Pakistan and Bangladesh, we conducted a quantitative content analysis
      in order to identify gender stereotypes in school education. In total, 21
      categories of exclusion and quality of representation were used to study gender
      stereotypes. Our analysis confirms a pro-male bias in textbooks: the aggregate
      female share is 40.4% in textual and pictorial indicators combined. Female
      occupations are mostly traditional and less prestigious while the characters are
      predominantly introverted and passive in terms of personality traits. Women are
      also shown to be mostly involved in domestic and in-door activities while men
      have a higher presence in professional roles. Systematic underrepresentation of
      females is evident regardless of whether we look at the text or pictures. A cross
      country analysis shows that the female share in picture content is only 35.2% in
      Malaysia and Bangladesh. Overall, the proportion of female to male characters
      (text and pictures combined) is balanced in Malaysia and Indonesia (44.4% and
      44.1% respectively) while this share is only 24.4% and 37.3% in Pakistani and
      Bangladeshi textbooks respectively. The finding of underrepresentation of women
      in Pakistani textbooks, in terms of quality and quantity, is robust to the
      selection of province-, grade- and subject-specific textbooks, as well as the
      range and type of categories used.

PMID- 29351306
TI  - An approach to localization for ensemble-based data assimilation.
AB  - Localization techniques are commonly used in ensemble-based data assimilation
      (e.g., the Ensemble Kalman Filter (EnKF) method) because of insufficient ensemble
      samples. They can effectively ameliorate the spurious long-range correlations
      between the background and observations. However, localization is very expensive
      when the problem to be solved is of high dimension (say 106 or higher) for
      assimilating observations simultaneously. To reduce the cost of localization for
      high-dimension problems, an approach is proposed in this paper, which
      approximately expands the correlation function of the localization matrix using a
      limited number of principal eigenvectors so that the Schur product between the
      localization matrix and a high-dimension covariance matrix is reduced to the sum
      of a series of Schur products between two simple vectors. These eigenvectors are
      actually the sine functions with different periods and phases. Numerical
      experiments show that when the number of principal eigenvectors used reaches 20,
      the approximate expansion of the correlation function is very close to the exact
      one in the one-dimensional (1D) and two-dimensional (2D) cases. The new approach
      is then applied to localization in the EnKF method, and its performance is
      evaluated in assimilation-cycle experiments with the Lorenz-96 model and single
      assimilation experiments using a barotropic shallow water model. The results
      suggest that the approach is feasible in providing comparable assimilation
      analysis with far less cost.

PMID- 29351307
TI  - Doxycycline modulates VEGF-A expression: Failure of doxycycline-inducible
      lentivirus shRNA vector to knockdown VEGF-A expression in transgenic mice.
AB  - Vascular endothelial growth factor-A (VEGF-A) is the master regulator of
      angiogenesis, vascular permeability and growth. However, its role in mature blood
      vessels is still not well understood. To better understand the role of VEGF-A in
      the adult vasculature, we generated a VEGF-A knockdown mouse model carrying a
      doxycycline (dox)-regulatable short hairpin RNA (shRNA) transgene, which silences
      VEGF-A. The aim was to find the critical level of VEGF-A reduction for vascular
      well-being in vivo. In vitro, the dox-inducible lentiviral shRNA vector decreased
      VEGF-A expression efficiently and dose-dependently in mouse endothelial cells and
      cardiomyocytes. In the generated transgenic mice plasma VEGF-A levels decreased
      shortly after the dox treatment but returned back to normal after two weeks. VEGF
      A expression decreased shortly after the dox treatment only in some tissues.
      Surprisingly, increasing the dox exposure time and dose led to elevated VEGF-A
      expression in some tissues of both wildtype and knockdown mice, suggesting that
      dox itself has an effect on VEGF-A expression. When the effect of dox on VEGF-A
      levels was further tested in naive/non-transduced cells, the dox administration
      led to a decreased VEGF-A expression in endothelial cells but to an increased
      expression in cardiomyocytes. In conclusion, the VEGF-A knockdown was achieved in
      a dox-regulatable fashion with a VEGF-A shRNA vector in vitro, but not in the
      knockdown mouse model in vivo. Dox itself was found to regulate VEGF-A expression
      explaining the unexpected results in mice. The effect of dox on VEGF-A levels
      might at least partly explain its previously reported beneficial effects on
      myocardial and brain ischemia. Also, this effect on VEGF-A should be taken into
      account in all studies using dox-regulated vectors.

PMID- 29351308
TI  - Skin transcriptome reveals the dynamic changes in the Wnt pathway during
      integument morphogenesis of chick embryos.
AB  - Avian species have a unique integument covered with feathers. Skin morphogenesis
      is a successive and complex process. To date, most studies have focused on a
      single developmental point or stage. Fewer studies have focused on whole
      transcriptomes based on the time-course of embryo integument development. To
      analyze the global changes in gene expression profiles, we sequenced the
      transcriptome of chicken embryo skin samples from day 6 to day 21 of incubation
      and identified 5830 differentially expressed genes (DEGs). Hierarchical
      clustering showed that E6 to E14 is the critical period of feather follicle
      morphogenesis. According to Kyoto Encyclopedia of Genes and Genomes (KEGG)
      pathway analysis of the DEGs, two kinds of Wnt signaling pathways (a canonical
      pathway and a non-canonical pathway) changed during feather follicle and feather
      morphogenesis. The gene expression level of inhibitors and ligands related to the
      Wnt signaling pathway varied significantly during embryonic development. The
      results revealed a staggered phase relationship between the canonical pathway and
      the non-canonical pathway from E9 to E14. These analyses shed new light on the
      gene regulatory mechanism and provided fundamental data related to integument
      morphogenesis of chickens.

PMID- 29351309
TI  - A modified elliptical formula to estimate kidney collagen content in a model of
      chronic kidney disease.
AB  - The extent of scarring or renal interstitial collagen deposition in chronic
      kidney disease (CKD) can only be ascertained by highly invasive, painful and
      sometimes risky, tissue biopsy. Interestingly, while CKD-related abnormalities in
      kidney size can often be visualized using ultrasound, not only does the ellipsoid
      formula used today underestimate true renal size, but the calculated renal size
      does not inform tubulointerstitial collagen content. We used coronal kidney
      sections from healthy mice and mice with kidney disease to develop a new formula
      for estimating renal parenchymal area. While treating the kidney as an ellipse
      with the major axis (a) the polar distance, this technique involves extending the
      minor axis (b) into the renal pelvis to obtain a new minor axis, be. The
      calculated renal parenchymal area is remarkably similar to the true or measured
      area. Biochemically determined kidney collagen content revealed a strong and
      positive correlation with the calculated renal parenchymal area. Picrosirius red
      staining for tubulointerstitial collagen also correlated with calculated renal
      parenchymal area. The extent of renal scarring, i.e. kidney interstitial collagen
      content, can now be computed by making just two axial measurements which can
      easily be accomplished via noninvasive imaging of this organ.

PMID- 29351310
TI  - Healthy ageing at work- Efficacy of group interventions on the mental health of
      nurses aged 45 and older: Results of a randomised, controlled trial.
AB  - OBJECTIVE: This multicentre, randomised controlled trial (RCT) aimed to evaluate
      the efficacy of a small-group intervention promoting successful ageing at work in
      older nurses (aged >=45). METHOD: A sample of 115 nurses aged >=45 from 4 trial
      sites in Germany were randomly assigned to either the intervention group (IG),
      that received a small-group intervention of seven weekly sessions of 120 min with
      a booster session after six weeks or to a wait-list control condition (WLC).
      Outcomes were measured via validated self-report questionnaires at baseline (T1)
      and at post-treatment (T2). Primary outcomes were mental health-related well
      being and mental health-related quality of life (QOL). The secondary outcomes
      included mental health-related and work-related measures. RESULTS: The intention
      to treat (ITT) analysis showed significant positive effects of the intervention
      on mental health. A significant small effect (d = 0.3) in favour of the IG was
      found for psychological health-related quality of life. Positive small effects (d
      = 0.24 to d = 0.31) were also found for work related mental strain. CONCLUSIONS:
      Our small-group intervention based on a theory of successful ageing for nurses
      aged >=45 was found to be effective with regard to improvements of psychological
      health related quality of life and other mental health-related outcomes. Thus,
      our study shows that the ageing workforce can be reached through specifically
      designed preventive interventions. The components of our intervention could be
      easily adapted to the belongings of other professions. Our results suggest that
      these components should be evaluated in various settings outside the healthcare
      sector.

PMID- 29351311
TI  - The quality of voluntary medical male circumcision done by mid-level workers in
      Tshwane District, South Africa: A retrospective analysis.
AB  - BACKGROUND: Voluntary medical male circumcision (VMMC) reduces the acquisition of
      human immunodeficiency virus (HIV) in heterosexual men by up to 60%. One HIV
      infection is averted for every 5 to 15 VMMCs. To conduct VMMCs in large
      populations, large numbers of trained healthcare professionals are needed.
      Countries in Sub-Saharan Africa have a high burden of HIV and a shortage of
      healthcare professionals, creating a healthcare conundrum. To bridge this gap,
      South Africa launched a new cadre of mid-level medical worker called Clinical
      Associates (CA). We assessed the ability of CAs to perform circumcisions of
      adequate quality and their subsequent usefulness to meet the demands of VMMCs in
      a population with a high HIV burden. METHODS: We conducted a retrospective
      analysis, reviewing patient files (n = 4850) of surgical VMMCs conducted over a
      16-month period. Patient files were sourced from clinics and hospitals that
      provided free VMMCs in Tshwane district in South Africa. FINDINGS: Clinical
      associates performed 88.66% of the circumcisions and doctors performed the
      remaining 11.34% (p < 0.001). The number of adverse events did not differ between
      the two groups. Data on intra-operative adverse events were available for 4 738
      patients. Of these, 341 (7.2%) experienced intra-operative adverse events. For
      the whole sample, 44 (8.1%, n = 543) adverse events occurred during circumcisions
      done by doctors and 297 (7.1%, n = 4195) occurred during circumcisions done by
      CAs (p = 0.385). Clinical associates performed circumcisions in shorter times
      (duration: 14.63 minutes) compared to doctors (duration: 15.25 minutes, t = 
      7.46; p < 0.001). Recorded pain, bleeding, swelling, infection and wound
      destruction did not differ between clients circumcised by CAs and doctors. This
      study is limited by the use of data from a single district. CONCLUSIONS: Clinical
      associates contribute to the demands for high numbers of VMMCs in Tshwane
      district, South Africa. Clinical associates perform VMMCs at a clinical standard
      that is comparable to circumcisions performed by doctors.

PMID- 29351312
TI  - Prognostic relevance of elevated pulmonary arterial pressure assessed non
      invasively: Analysis in a large patient cohort with invasive measurements in near
      temporal proximity.
AB  - BACKGROUND: The clinical relevance of non-invasively derived pulmonary arterial
      pressure (PAP) by Doppler echocardiography (DE) has been questioned in the past.
      However, transthoracic echocardiography is used as a cornerstone examination for
      patients with dyspnea and suspected pulmonary hypertension (PH). This study aimed
      to evaluate the prognostic value of non-invasive assessed PAP in a large
      population of patients with known or suspected cardiopulmonary disease. METHODS:
      The analyses are based on data of patients of a tertiary cardiology center that
      received right heart catheterization (RHC) as well as non-invasively assessed PAP
      by DE within five days, and includes serological and clinical parameters in a
      retrospective follow-up for up to eight years. RESULTS: Of 1,237 patients,
      clinical follow-up was possible in 1,038 patients who were included in the
      statistical analysis. The mean-follow up time was 1,002 days. The composite
      endpoint of heart transplantation (HTx) or death occurred in n = 308 patients.
      Elevated PAP measured non-invasively as well as invasively had significant
      prognostic impact (hazard ratio (HR) 2.32; 95% confidence interval (CI) 1.78
      3.04; chi2 = 37.9; p<0.001 versus HR 2.84; 95%CI 2.11-3.82; chi2 = 51.9; p<0.001,
      respectively). By multivariate analysis, NYHA functional class, N-terminal pro
      brain natriuretic peptide, cardiac troponin T, left ventricular ejection
      fraction, and right ventricular dysfunction remained independently predictive.
      Incremental prognostic information in a multimodal approach was highly relevant.
      CONCLUSIONS: In this comprehensive study, elevated pulmonary arterial pressure
      measured by DE offers similar prognostic information on survival or need for HTx
      as right heart catheterization. Furthermore, the addition of functional capacity
      and serological biomarkers delivered incremental prognostic information.

PMID- 29351313
TI  - Effectiveness and safety of early medication abortion provided in pharmacies by
      auxiliary nurse-midwives: A non-inferiority study in Nepal.
AB  - BACKGROUND: Expanding access to medication abortion through pharmacies is a
      promising avenue to reach women with safe and convenient care, yet no pharmacy
      provision interventions have been evaluated. This observational non-inferiority
      study investigated the effectiveness and safety of mifepristone-misoprostol
      medication abortion provided at pharmacies, compared to government-certified
      public health facilities, by trained auxiliary nurse-midwives in Nepal. METHODS:
      Auxiliary nurse-midwives were trained to provide medication abortion through
      twelve pharmacies and public facilities as part of a demonstration project in two
      districts. Eligible women were <=63 days pregnant, aged 16-45, and had no medical
      contraindications. Between 2014-2015, participants (n = 605) obtained 200 mg
      mifepristone orally and 800 MUg misoprostol sublingually or intravaginally 24
      hours later, and followed-up 14-21 days later. The primary outcome was complete
      abortion without manual vacuum aspiration; the secondary outcome was complication
      requiring treatment. We assessed risk differences by facility type with
      multivariable logistic mixed-effects regression. RESULTS: Over 99% of enrolled
      women completed follow-up (n = 600). Complete abortions occurred in 588 (98.0%)
      cases, with ten incomplete abortions and two continuing pregnancies. 293/297
      (98.7%) pharmacy participants and 295/303 (97.4%) public facility participants
      had complete abortions, with an adjusted risk difference falling within the pre
      specified 5 percentage-point non-inferiority margin (1.5% [-0.8%, 3.8%]). No
      serious adverse events occurred. Five (1.7%) pharmacy and two (0.7%) public
      facility participants experienced a complication warranting treatment (aRD, 0.8%
      [-1.0%-2.7%]). CONCLUSIONS: Early mifepristone-misoprostol abortion was as
      effective and safe when provided by trained auxiliary nurse-midwives at
      pharmacies as at government-certified health facilities. Findings support policy
      expanding provision through registered pharmacies by trained auxiliary nurse
      midwives to improve access to safe care.

PMID- 29351314
TI  - Species richness of Eurasian Zephyrus hairstreaks (Lepidoptera: Lycaenidae:
      Theclini) with implications on historical biogeography: An NDM/VNDM approach.
AB  - AIM: A database based on distributional records of Eurasian Zephyrus hairstreaks
      (Lepidoptera: Lycaenidae: Theclini) was compiled to analyse their areas of
      endemism (AoEs), species richness and distribution patterns, to explore their
      locations of past glacial refugia and dispersal routes. METHODS: Over 2000
      Zephyrus hairstreaks occurrences are analysed using the NDM/VNDM algorithm, for
      the recognition of AoEs. Species richness was calculated by using the option
      'Number of different classes' to count the different classes of a variable
      presented in each 3.0 degrees *3.0 degrees  grid cell, and GIS software was used
      to visualize distribution patterns of endemic species. RESULTS: Centres of
      species richness of Zephyrus hairstreaks are situated in the eastern Qinghai
      Tibet Plateau (EQTP), Hengduan Mountain Region (HDMR) and the Qinling Mountain
      Region (QLMR). Latitudinal gradients in species richness show normal distribution
      with the peak between 25 degrees  N and 35 degrees  N in the temperate zone,
      gradually decreasing towards the poles. Moreover, most parts of central and
      southern China, especially the area of QLMR-EQTP-HDMR, were identified as AoEs
      that may have played a significant role as refugia during Quaternary global
      cooling. There are four major distributional patterns of Zephyrus hairstreaks in
      Eurasia: Sino-Japanese, Sino-Himalayan, high-mountain and a combined distribution
      covering all three patterns. CONCLUSIONS: Zephyrus hairstreaks probably
      originated at least 23-24 Myr ago in E. Asia between 25 degrees  N to 35 degrees 
      N in the temperate zone. Cenozoic orogenies caused rapid speciation of this tribe
      and extrusion of the Indochina block resulted in vicariance between the Sino
      Japanese and the Sino-Himalayan patterns. The four distribution patterns provided
      two possible dispersal directions: Sino-Japanese dispersal and Sino-Himalayan
      dispersal.

PMID- 29351315
TI  - Large-scale mapping of bioactive peptides in structural and sequence space.
AB  - Health-enhancing potential bioactive peptide (BP) has driven an interest in food
      proteins as well as in the development of predictive methods. Research in this
      area has been especially active to use them as components in functional foods.
      Apparently, BPs do not have a given biological function in the containing
      proteins and they do not evolve under independent evolutionary constraints. In
      this work we performed a large-scale mapping of BPs in sequence and structural
      space. Using well curated BP deposited in BIOPEP database, we searched for exact
      matches in non-redundant sequences databases. Proteins containing BPs, were used
      in fold-recognition methods to predict the corresponding folds and BPs
      occurrences were mapped. We found that fold distribution of BP occurrences
      possibly reflects sequence relative abundance in databases. However, we also
      found that proteins with 5 or more than 5 BP in their sequences correspond to
      well populated protein folds, called superfolds. Also, we found that in well
      populated superfamilies, BPs tend to adopt similar locations in the protein fold,
      suggesting the existence of hotspots. We think that our results could contribute
      to the development of new bioinformatics pipeline to improve BP detection.

PMID- 29351316
TI  - Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness
      behavior, and anhedonia.
AB  - BACKGROUND: Peripheral innate immune response may induce sickness behavior
      through activating microglia, excessive cytokines production, and
      neuroinflammation. Dexmedetomidine (Dex) has anti-inflammatory effect. We
      investigated the effects of Dex on lipopolysaccharide (LPS)-induced
      neuroinflammation and sickness behavior in mice. MATERIALS AND METHODS: BALB/c
      mice were intraperitoneally (i.p.) injected with Dex (50 ug/kg) or vehicle. One
      hour later, the mice were injected (i.p.) with Escherichia coli LPS (0.33 mg/kg)
      or saline (n = 6 in each group). We analyzed the food and water intake, body
      weight loss, and sucrose preference of the mice for 24h. We also determined
      microglia activation and cytokines expression in the brains of the mice. In
      vitro, we determine cytokines expression in LPS-treated BV-2 microglial cells
      with or without Dex treatment. RESULTS: In the Dex-pretreated mice, LPS-induced
      sickness behavior (anorexia, weight loss, and social withdrawal) were attenuated
      and microglial activation was lower than vehicle control. The mRNA expression of
      TNF-alpha, MCP-1, indoleamine 2, 3 dioxygenase (IDO), caspase-3, and iNOS were
      increased in the brain of LPS-challenged mice, which were reduced by Dex but not
      vehicle. CONCLUSION: Dexmedetomidine diminished LPS-induced neuroinflammation in
      the mouse brain and modulated the cytokine-associated changes in sickness
      behavior.

PMID- 29351317
TI  - HAfTs are novel lncRNA transcripts from aflatoxin exposure.
AB  - The transcriptome can reveal insights into precancer biology. We recently
      conducted RNA-Seq analysis on liver RNA from male rats exposed to the carcinogen,
      aflatoxin B1 (AFB1), for 90 days prior to liver tumor onset. Among >1,000
      differentially expressed transcripts, several novel, unannotated Cufflinks
      assembled transcripts, or HAfTs (Hepatic Aflatoxin Transcripts) were found. We
      hypothesized PCR-cloning and RACE (rapid amplification of cDNA ends) could
      further HAfT identification. Sanger data was obtained for 6 transcripts by PCR
      and 16 transcripts by 5'- and 3'-RACE. BLAST alignments showed, with two
      exceptions, HAfT transcripts were lncRNAs, >200nt without apparent long open
      reading frames. Six rat HAfT transcripts were classified as 'novel' without
      RefSeq annotation. Sequence alignment and genomic synteny showed each rat lncRNA
      had a homologous locus in the mouse genome and over half had homologous loci in
      the human genome, including at least two loci (and possibly three others) that
      were previously unannotated. While HAfT functions are not yet clear, coregulatory
      roles may be possible from their adjacent orientation to known coding genes with
      altered expression that include 8 HAfT-gene pairs. For example, a unique rat
      HAfT, homologous to Pvt1, was adjacent to known genes controlling cell
      proliferation. Additionally, PCR and RACE Sanger sequencing showed many
      alternative splice variants and refinements of exon sequences compared to
      Cufflinks assembled transcripts and gene prediction algorithms. Presence of
      multiple splice variants and short tandem repeats found in some HAfTs may be
      consequential for secondary structure, transcriptional regulation, and function.
      In summary, we report novel, differentially expressed lncRNAs after exposure to
      the genotoxicant, AFB1, prior to neoplastic lesions. Complete cloning and
      sequencing of such transcripts could pave the way for a new set of sensitive and
      early prediction markers for chemical hepatocarcinogens.

PMID- 29351319
TI  - Speech, stone tool-making and the evolution of language.
AB  - The 'technological hypothesis' proposes that gestural language evolved in early
      hominins to enable the cultural transmission of stone tool-making skills, with
      speech appearing later in response to the complex lithic industries of more
      recent hominins. However, no flintknapping study has assessed the efficiency of
      speech alone (unassisted by gesture) as a tool-making transmission aid. Here we
      show that subjects instructed by speech alone underperform in stone tool-making
      experiments in comparison to subjects instructed through either gesture alone or
      'full language' (gesture plus speech), and also report lower satisfaction with
      their received instruction. The results provide evidence that gesture was likely
      to be selected over speech as a teaching aid in the earliest hominin tool-makers;
      that speech could not have replaced gesturing as a tool-making teaching aid in
      later hominins, possibly explaining the functional retention of gesturing in the
      full language of modern humans; and that speech may have evolved for reasons
      unrelated to tool-making. We conclude that speech is unlikely to have evolved as
      tool-making teaching aid superior to gesture, as claimed by the technological
      hypothesis, and therefore alternative views should be considered. For example,
      gestural language may have evolved to enable tool-making in earlier hominins,
      while speech may have later emerged as a response to increased trade and more
      complex inter- and intra-group interactions in Middle Pleistocene ancestors of
      Neanderthals and Homo sapiens; or gesture and speech may have evolved in parallel
      rather than in sequence.

PMID- 29351318
TI  - Invasive bacterial disease trends and characterization of group B streptococcal
      isolates among young infants in southern Mozambique, 2001-2015.
AB  - BACKGROUND: Maternal group B streptococcal (GBS) vaccines under development hold
      promise to prevent GBS disease in young infants. Sub-Saharan Africa has the
      highest estimated disease burden, although data on incidence and circulating
      strains are limited. We described invasive bacterial disease (IBD) trends among
      infants <90 days in rural Mozambique during 2001-2015, with a focus on GBS
      epidemiology and strain characteristics. METHODS: Community-level birth and
      mortality data were obtained from Manhica's demographic surveillance system. IBD
      cases were captured through ongoing surveillance at Manhica district hospital.
      Stored GBS isolates from cases underwent serotyping by multiplex PCR,
      antimicrobial susceptibility testing, and whole genome sequencing. RESULTS: There
      were 437 IBD cases, including 57 GBS cases. Significant declines in overall IBD,
      neonatal mortality, and stillbirth rates were observed (P<0.0001), but not for
      GBS (P = 0.17). In 2015, GBS was the leading cause of young infant IBD (2.7 per
      1,000 live births). Among 35 GBS isolates available for testing, 31 (88.6%) were
      highly related serotype III isolates within multilocus sequence types (STs) 17
      (68.6%) or 109 (20.0%). All seven ST109 isolates (21.9%) had elevated minimum
      inhibitory concentration (MIC) to penicillin (>=0.12 MUg/mL) associated with
      penicillin-binding protein (PBP) 2x substitution G398A. Epidemiologic and
      molecular data suggest this is a well-established clone. CONCLUSION: A notable
      young infant GBS disease burden persisted despite improvements in overall
      maternal and neonatal health. We report an established strain with pbp2x point
      mutation, a first-step mutation associated with reduced penicillin susceptibility
      within a well-known virulent lineage in rural Mozambique. Our findings further
      underscores the need for non-antibiotic GBS prevention strategies.

PMID- 29351320
TI  - Coiled-coil formation of the membrane-fusion K/E peptides viewed by electron
      paramagnetic resonance.
AB  - The interaction of the complementary K (Ac-(KIAALKE)3-GW-NH2) and E (Ac
      (EIAALEK)3-GY-NH2) peptides, components of the zipper of an artificial membrane
      fusion system (Robson Marsden H. et al. Angew Chemie Int Ed. 2009) is
      investigated by electron paramagnetic resonance (EPR). By frozen solution
      continuous-wave EPR and double electron-electron resonance (DEER), the distance
      between spin labels attached to the K- and to the E-peptide is measured. Three
      constructs of spin-labelled K- and E-peptides are used in five combinations for
      low temperature investigations. The K/E heterodimers are found to be parallel, in
      agreement with previous studies. Also, K homodimers in parallel orientation were
      observed, a finding that was not reported before. Comparison to room-temperature,
      solution EPR shows that the latter method is less specific to detect this peptide
      peptide interaction. Combining frozen solution cw-EPR for short distances (1.8 nm
      to 2.0 nm) and DEER for longer distances thus proves versatile to detect the
      zipper interaction in membrane fusion. As the methodology can be applied to
      membrane samples, the approach presented suggests itself for in-situ studies of
      the complete membrane fusion process, opening up new avenues for the study of
      membrane fusion.

PMID- 29351321
TI  - Methylglyoxal produces more changes in biochemical and biophysical properties of
      human IgG under high glucose compared to normal glucose level.
AB  - Hyperglycaemia triggers increased production of methylglyoxal which can cause
      gross modification in proteins' structure vis-a-vis function though advanced
      glycation end products (AGEs). The AGEs may initiate vascular and nonvascular
      pathologies. In this study, we have examined the biochemical and biophysical
      changes in human IgG under normal and high glucose after introducing
      methylglyoxal into the assay mixture. This non-enzymatic reaction mainly engaged
      lysine residues as indicated by TNBS results. The UV results showed
      hyperchromicity in modified-IgG samples while fluorescence data supported AGEs
      formation during the course of reaction. Shift in amide I and amide II band
      position indicated perturbations in secondary structure. Increase carbonyl
      content and decrease in sulfhydryl suggests that the modification is accompanied
      by oxidative stress. All modified-IgG samples showed more thermostability than
      native IgG; the highest Tm was shown by IgG-high glucose-MGO variant. Results of
      ANS, Congo red and Thioflavin T dyes clearly suggest increase in hydrophobic
      patches and aggregation, respectively. SEM and TEM images support aggregates
      generation in modified-IgG samples.

PMID- 29351322
TI  - Influence of multiplicative stochastic variation on translational elongation
      rates.
AB  - Experimental data indicate that stochastic effects exerted at the level of
      translation contribute substantially to the variation in abundance of proteins
      expressed at moderate to high levels. This study analyzes the theoretical
      consequences of fluctuations in residue-specific elongation rates during
      translation. A simple analytical framework shows that rate variation during
      elongation gives rise to protein production rates that consist of sums of
      products of random variables. Simulations show that because the contribution to
      total variation of products of random variables greatly exceeds that of sums of
      random variables, the overall distribution exhibits approximately log-normal
      behavior. Empirical fits of the data can be satisfied by either sums of log
      normal distributions, or sums of log-normal and log-logistic distributions.
      Elongation rate stochastic variation offers an accounting for a major component
      of biological variation. The analysis provided here highlights a probability
      distribution that is a natural extension of the Poisson and has broad
      applicability to many types of multiplicative noise processes.

PMID- 29351323
TI  - Fire forbids fifty-fifty forest.
AB  - Recent studies have interpreted patterns of remotely sensed tree cover as
      evidence that forest with intermediate tree cover might be unstable in the
      tropics, as it will tip into either a closed forest or a more open savanna state.
      Here we show that across all continents the frequency of wildfires rises sharply
      as tree cover falls below ~40%. Using a simple empirical model, we hypothesize
      that the steepness of this pattern causes intermediate tree cover (30-60%) to be
      unstable for a broad range of assumptions on tree growth and fire-driven
      mortality. We show that across all continents, observed frequency distributions
      of tropical tree cover are consistent with this hypothesis. We argue that
      percolation of fire through an open landscape may explain the remarkably
      universal rise of fire frequency around a critical tree cover, but we show that
      simple percolation models cannot predict the actual threshold quantitatively. The
      fire-driven instability of intermediate states implies that tree cover will not
      change smoothly with climate or other stressors and shifts between closed forest
      and a state of low tree cover will likely tend to be relatively sharp and
      difficult to reverse.

PMID- 29351324
TI  - Abnormal network flow detection based on application execution patterns from Web
      of Things (WoT) platforms.
AB  - In this paper, we present a research work on a novel methodology of identifying
      abnormal behaviors at the underlying network monitor layer during runtime based
      on the execution patterns of Web of Things (WoT) applications. An execution
      pattern of a WoT application is a sequence of profiled time delays between the
      invocations of involved Web services, and it can be obtained from WoT platforms.
      We convert the execution pattern to a time sequence of network flows that are
      generated when the WoT applications are executed. We consider such time sequences
      as a whitelist. This whitelist reflects the valid application execution patterns.
      At the network monitor layer, our applied RETE algorithm examines whether any
      given runtime sequence of network flow instances does not conform to the
      whitelist. Through this approach, it is possible to interpret a sequence of
      network flows with regard to application logic. Given such contextual
      information, we believe that the administrators can detect and reason about any
      abnormal behaviors more effectively. Our empirical evaluation shows that our RETE
      based algorithm outperforms the baseline algorithm in terms of memory usage.

PMID- 29351326
TI  - Increased natural reproduction and genetic diversity one generation after
      cessation of a steelhead trout (Oncorhynchus mykiss) conservation hatchery
      program.
AB  - Spatial and temporal fluctuations in productivity and abundance confound
      assessments of captive propagation programs aimed at recovery of Threatened and
      Endangered populations. We conducted a 17 year before-after-control-impact
      experiment to determine the effects of a captive rearing program for anadromous
      steelhead trout (Oncorhynchus mykiss) on a key indicator of natural spawner
      abundance (naturally produced nests or 'redds'). The supplemented population
      exhibited a significant (2.6-fold) increase in redd abundance in the generation
      following supplementation. Four non-supplemented (control) populations monitored
      over the same 17 year period exhibited stable or decreasing trends in redd
      abundance. Expected heterozygosity in the supplemented population increased
      significantly. Allelic richness increased, but to a lesser (non-significant)
      degree. Estimates of the effective number of breeders increased from a harmonic
      mean of 24.4 in the generation before supplementation to 38.9 after
      supplementation. Several non-conventional aspects of the captive rearing program
      may have contributed to the positive response in the natural population.

PMID- 29351325
TI  - Impact of educational interventions on adolescent attitudes and knowledge
      regarding vaccination: A pilot study.
AB  - BACKGROUND: Current immunisation levels in England currently fall slightly below
      the threshold recommended by the World Health Organization, and the three-year
      trend for vaccination uptake is downwards. Attitudes towards vaccination can
      affect future decisions on whether or not to vaccinate, and this can have
      significant public health implications. Interventions can impact future
      vaccination decisions, and these interventions can take several forms. Relatively
      little work has been reported on the use of vaccination interventions in young
      people, who form the next generation of individuals likely to make vaccination
      decisions. METHOD: We investigated the impact of two different types of
      educational intervention on attitudes towards vaccination in young people in
      England. A cohort of young people (n = 63) was recruited via a local school. This
      group was divided into three sub-groups; one (n = 21) received a presentation
      based intervention, one (n = 26) received an interactive simulation-based
      intervention, and the third (n = 16) received no intervention. Participants
      supplied information on (1) their attitudes towards vaccination, and (2) their
      information needs and views on personal choice concerning vaccination, at three
      time points: immediately before and after the intervention, and after six months.
      RESULTS: Neither intervention had a significant effect on participants' attitudes
      towards vaccination. However, the group receiving the presentation-based
      intervention saw a sustained uplift in confidence about information needs, which
      was not observed in the simulation-based intervention group. DISCUSSION: Our
      findings with young people are consistent with previous work on vaccination
      interventions aimed at adults, which have shown limited effectiveness, and which
      can actually reduce intention to vaccinate. Our findings on the most effective
      mode of delivery for the intervention should inform future discussion in the
      growing "games for health" domain, which proposes the use of interactive digital
      resources in healthcare education.

PMID- 29351327
TI  - A novel risk classification system for 30-day mortality in children undergoing
      surgery.
AB  - A simple, objective and accurate way of grouping children undergoing surgery into
      clinically relevant risk groups is needed. The purpose of this study, is to
      develop and validate a preoperative risk classification system for postsurgical
      30-day mortality for children undergoing a wide variety of operations. The
      National Surgical Quality Improvement Project-Pediatric participant use file data
      for calendar years 2012-2014 was analyzed to determine preoperative variables
      most associated with death within 30 days of operation (D30). Risk groups were
      created using classification tree analysis based on these preoperative variables.
      The resulting risk groups were validated using 2015 data, and applied to neonates
      and higher risk CPT codes to determine validity in high-risk subpopulations. A
      five-level risk classification was found to be most accurate. The preoperative
      need for ventilation, oxygen support, inotropic support, sepsis, the need for
      emergent surgery and a do not resuscitate order defined non-overlapping groups
      with observed rates of D30 that vary from 0.075% (Very Low Risk) to 38.6% (Very
      High Risk). When CPT codes where death was never observed are eliminated or when
      the system is applied to neonates, the groupings remained predictive of death in
      an ordinal manner.

PMID- 29351328
TI  - Joint modeling of correlated binary outcomes: The case of contraceptive use and
      HIV knowledge in Bangladesh.
AB  - Recent advances in statistical methods enable the study of correlation among
      outcomes through joint modeling, thereby addressing spillover effects. By joint
      modeling, we refer to simultaneously analyzing two or more different response
      variables emanating from the same individual. Using the 2011 Bangladesh
      Demographic and Health Survey, we jointly address spillover effects between
      contraceptive use (CUC) and knowledge of HIV and other sexually transmitted
      diseases. Jointly modeling these two outcomes is appropriate because certain
      types of contraceptive use contribute to the prevention of HIV and STDs and the
      knowledge and awareness of HIV and STDs typically lead to protection during
      sexual intercourse. In particular, we compared the differences as they pertained
      to the interpretive advantage of modeling the spillover effects of joint modeling
      HIV and CUC as opposed to addressing them separately. We also identified risk
      factors that determine contraceptive use and knowledge of HIV and STDs among
      women in Bangladesh. We found that by jointly modeling the correlation between
      HIV knowledge and contraceptive use, the importance of education decreased. The
      HIV prevention program had a spillover effect on CUC: what seemed to be impacted
      by education can be partially contributed to one's exposure to HIV knowledge. The
      joint model revealed a less significant impact of covariates as opposed to both
      separate models and standard models. Additionally, we found a spillover effect
      that would have otherwise been undiscovered if we did not jointly model. These
      findings further suggested that the simultaneous impact of correlated outcomes
      can be adequately addressed for the commonality between different responses and
      deflate, which is otherwise overestimated when examined separately.

PMID- 29351329
TI  - Radiocarbon dating uncertainty and the reliability of the PEWMA method of time
      series analysis for research on long-term human-environment interaction.
AB  - Statistical time-series analysis has the potential to improve our understanding
      of human-environment interaction in deep time. However, radiocarbon dating-the
      most common chronometric technique in archaeological and palaeoenvironmental
      research-creates challenges for established statistical methods. The methods
      assume that observations in a time-series are precisely dated, but this
      assumption is often violated when calibrated radiocarbon dates are used because
      they usually have highly irregular uncertainties. As a result, it is unclear
      whether the methods can be reliably used on radiocarbon-dated time-series. With
      this in mind, we conducted a large simulation study to investigate the impact of
      chronological uncertainty on a potentially useful time-series method. The method
      is a type of regression involving a prediction algorithm called the Poisson
      Exponentially Weighted Moving Average (PEMWA). It is designed for use with count
      time-series data, which makes it applicable to a wide range of questions about
      human-environment interaction in deep time. Our simulations suggest that the
      PEWMA method can often correctly identify relationships between time-series
      despite chronological uncertainty. When two time-series are correlated with a
      coefficient of 0.25, the method is able to identify that relationship correctly
      20-30% of the time, providing the time-series contain low noise levels. With
      correlations of around 0.5, it is capable of correctly identifying correlations
      despite chronological uncertainty more than 90% of the time. While further
      testing is desirable, these findings indicate that the method can be used to test
      hypotheses about long-term human-environment interaction with a reasonable degree
      of confidence.

PMID- 29351330
TI  - Use of influenza antivirals in patients hospitalized in Hong Kong, 2000-2015.
AB  - OBJECTIVES: We aimed to describe patterns in the usage of antivirals to treat
      influenza virus infection in hospitals in Hong Kong from 2000 through 2015.
      METHODS: We analyzed centralized electronic health records that included
      dispensation information and diagnosis codes. Information collected on admissions
      included patient age, sex, admission year and month, and medications dispensed,
      and were matched with the first 15 discharge diagnosis codes. We divided monthly
      admission episodes by relevant population denominators to obtain admission rates,
      and stratified analyses by drug type, age group, and diagnosis codes. RESULTS:
      Amantadine was used for influenza treatment in the early 2000s but changed with
      recommendations to avoid its use in 2006, and is now mainly used to treat
      Parkinson's disease. Oseltamivir usage increased substantially in 2009 and is now
      commonly used, with almost 40,000 hospitalizations treated with oseltamivir in
      the years 2012 through 2015, 66% of which was in persons >=65 years of age.
      During the entire study period, of the 98,253 admission episodes in which
      oseltamivir was dispensed, 40,698 (41%) included a diagnosis code for influenza,
      and 80,283 (82%) included any diagnosis code for respiratory illness.
      CONCLUSIONS: The amount of oseltamivir used from 2012-15 was comparable to a
      separate ecological estimate of around 13,000 influenza-associated
      hospitalizations per year on average. We did not have access to individual
      patient laboratory testing data.

PMID- 29351331
TI  - The association between previous and future severe exacerbations of chronic
      obstructive pulmonary disease: Updating the literature using robust statistical
      methodology.
AB  - BACKGROUND: There is minimal evidence on the extent to which the occurrence of a
      severe acute exacerbation of COPD that results in hospitalization affects the
      subsequent disease course. Previous studies on this topic did not generate
      causally-interpretable estimates. Our aim was to use corrected methodology to
      update previously reported estimates of the associations between previous and
      future exacerbations in these patients. METHODS: Using administrative health data
      in British Columbia, Canada (1997-2012), we constructed a cohort of patients with
      at least one severe exacerbation, defined as an episode of inpatient care with
      the main diagnosis of COPD based on international classification of diseases
      (ICD) codes. We applied a random-effects 'joint frailty' survival model that is
      particularly developed for the analysis of recurrent events in the presence of
      competing risk of death and heterogeneity among individuals in their rate of
      events. Previous severe exacerbations entered the model as dummy-coded time
      dependent covariates, and the model was adjusted for several observable patient
      and disease characteristics. RESULTS: 35,994 individuals (mean age at baseline
      73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe
      exacerbations during follow-up. The first event was associated with a hazard
      ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations.
      This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to
      1.18 (95%CI 1.12-1.25) for the third event. The first two severe exacerbations
      that occurred during follow-up were also significantly associated with increased
      risk of all-cause mortality. There was substantial heterogeneity in the
      individual-specific rate of severe exacerbations. Even after adjusting for
      observable characteristics, individuals in the 97.5th percentile of exacerbation
      rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th
      percentile. CONCLUSIONS: Using robust statistical methodology that controlled for
      heterogeneity in exacerbation rates among individuals, we demonstrated potential
      causal associations among past and future severe exacerbations, albeit the
      magnitude of association was noticeably lower than previously reported. The
      prevention of severe exacerbations has the potential to modify the disease
      trajectory.

PMID- 29351332
TI  - Impedance spectroscopy of single bacterial nanofilament reveals water-mediated
      charge transfer.
AB  - For decades respiratory chain and photosystems were the main firing field of the
      studies devoted to mechanisms of electron transfer in proteins. The concept of
      conjugated lateral electron and transverse proton transport during cellular
      respiration and photosynthesis, which was formulated in the beginning of 1960-s,
      has been confirmed by thousands of experiments. However, charge transfer in
      recently discovered bacterial nanofilaments produced by various electrogenic
      bacteria is regarded currently outside of electron and proton conjugation
      concept. Here we report the new study of charge transfer within nanofilaments
      produced by Shewanella oneidensis MR-1 conducted in atmosphere of different
      relative humidity (RH). We utilize impedance spectroscopy and DC (direct current)
      transport measurements to find out the peculiarities of conductivity and Raman
      spectroscopy to analyze the nanofilaments' composition. Data analysis
      demonstrates that apparent conductivity of nanofilaments has crucial sensitivity
      to humidity and contains several components including one with unusual behavior
      which we assign to electron transport. We demonstrate that in the case of
      Shewanella oneidensis MR-1 charge transfer within these objects is strongly
      mediated by water. Basing on current data analysis of conductivity we conclude
      that the studied filaments of Shewanella oneidensis MR-1 are capable of hybrid
      (conjugated) electron and ion conductivity.

PMID- 29351333
TI  - Simultaneous quantification of four antiretroviral drugs in breast milk samples
      from HIV-positive women by an ultra-high performance liquid chromatography tandem
      mass spectrometry (UPLC-MS/MS) method.
AB  - The primary strategy to avoid mother-to-child transmission of human
      immunodeficiency virus (HIV) through breastfeeding is administration of highly
      active antiretroviral therapy (HAART) to HIV-positive pregnant women. Because
      significant changes in the pharmacokinetics of antiretroviral (ARV) drugs occur
      during pregnancy, quantifying HAART and the viral load in breast milk in this
      population is essential. Here, we developed an analytical assay for the
      simultaneous quantification of four ARV drugs in breast milk using ultra
      performance liquid chromatography coupled to tandem mass spectrometry. We
      validated this method following Mexican and international guidelines. ARV drugs.
      We extracted the ARV drugs from 200 MUL samples of breast milk and detected these
      drugs in a triple quadrupole mass spectrometer with positive electrospray
      ionization. The validated concentration ranges (ng/mL) for zidovudine,
      lamivudine, lopinavir, and ritonavir were 12.5-750, 50-2500, 100-5000 and 5 to
      250, respectively. Additionally, the absolute recovery percentages (and matrix
      effects) were 91.4 (8.39), 88.78 (28.75), 91.38 (11.77) and 89.78 (12.37),
      respectively. We determined that ARV drugs are stable for 24 h at 8 degrees C and
      24 degrees C for 15 days at -80 degrees C. This methodology had the capacity for
      simultaneous detection; separation; and accurate, precise quantification of ARV
      drugs in human breast milk samples according to Mexican standard laws and United
      States Food and Drug Administration guidelines.

PMID- 29351334
TI  - Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy
      membranes.
AB  - PURPOSE: To characterize the relationship between endothelin-1 and fibrosis in
      epiretinal membranes in proliferative diabetic retinopathy and explore the role
      of endothelial-mesenchymal transition in these membranes. METHODS: Membranes were
      obtained from eyes undergoing pars plana vitrectomy for complicated proliferative
      diabetic retinopathy or idiopathic epiretinal membrane. Through standard
      immunohistochemical techniques, we labeled membranes to explore the distribution
      of endothelin-1 and endothelin receptor B, comparing proliferative diabetic
      retinopathy and idiopathic epiretinal membranes. In addition, membranes were also
      labeled with markers for fibroblasts, endothelial, and glial cells and studied
      with confocal laser scanning microscopy. The intensity of endothelin-1 labeling
      was quantified using standard image analysis software. RESULTS: Fourteen
      membranes were included in the analysis, nine from eyes with proliferative
      diabetic retinopathy and five idiopathic membranes. Flatmount diabetic membranes
      showed co-localization of endothelin-1 with S100A4 and CD31. Immunohistochemistry
      and quantitative analysis of cross-sectional membranes showed significantly
      higher endothelin-1 labeling in proliferative diabetic retinopathy membranes
      compared to idiopathic membranes (p<0.05). Diabetic membranes showed more
      elements staining positive for S100A4 compared to idiopathic membranes.
      CONCLUSION: Epiretinal membrane formation in proliferative diabetic retinopathy
      involves higher tissue levels of endothelin-1 and fibroblastic activity.
      Furthermore, endothelin-1, endothelial and fibroblastic staining appear to be
      correlated, suggestive of endothelial-to-mesenchymal transition in proliferative
      diabetic retinopathy.

PMID- 29351335
TI  - The effects of an acute exercise bout on GH and IGF-1 in prediabetic and healthy
      African Americans: A pilot study investigating gene expression.
AB  - : The incidence of pre-diabetes (PD) and Type-2 Diabetes Mellitus (T2D) is a
      worldwide epidemic. African American (AA) individuals are disproportionately more
      likely to become diabetic than other ethnic groups. Over the long-term, metabolic
      complications related to diabetes result in significant alterations in growth
      hormone (GH) and insulin-like growth factor-1 (IGF-1). Considering the limited
      exercise-related studies in the area of gene expression changes with disease
      progression, the objective of this study was to examine differences in exercise
      induced gene expression related to the GH and IGF-1 pathways in peripheral blood
      mononuclear cells (PBMCs) of healthy (CON) and PD AA individuals. DESIGN: Ten
      subjects [5 PD (age = 35+/-9.3 yr, BMI = 32.1+/-4.0, FBG = 101.8+/-1.3 mg/dl) and
      5 CON (age = 31+/-9.4 yr, BMI = 29.4+/-5.2, FBG = 82.8+/-9.7 mg/dl)] had blood
      drawn for RNA isolation prior to exercise (Pre), immediately following acute
      moderate intensity exercise on a treadmill (Post-1), 6-hours post (Post-6), and
      24-hours post (Post-24). Isolation of mRNA from PBMCs was performed using ficoll
      separation, while the profiling of mRNA expression was performed using Illumina
      beadchip arrays with standard protocols. Scan results were statistically analyzed
      for a specific list of genes related to GH and IGF-1. GH and IGF-1 protein levels
      were also assessed in each sample. To address issues of normality, all GH and IGF
      1 data were log-transformed prior to analysis. Statistical significance was set
      at p<0.05. RESULTS: Group differences for GH2 variant 2 (p = 0.070) and GH2
      variant 3 (p = 0.059) were coupled with significant alterations in IGF-1 mRNA
      over time (p = 0.024). A significant interaction between group and time was
      observed for GHRH mRNA (p = 0.008). No group differences were observed in GH AUC
      (p = 0.649), DeltaGH (p = 0.331), GHrec (p = 0.294), or IGF-1 AUC (p = 0.865),
      representing a similar exercise-induced GH and IGF-1 response for both groups.
      CONCLUSIONS: Analysis of GH and IGF-1 related-gene expression indicates that mild
      elevations in fasting blood glucose and exercise-induced alterations in gene
      expression are impacted by the prediabetic state.

PMID- 29351336
TI  - Chemotactic drift speed for bacterial motility pattern with two alternating
      turning events.
AB  - Bacterial chemotaxis is one of the most extensively studied adaptive responses in
      cells. Many bacteria are able to bias their apparently random motion to produce a
      drift in the direction of the increasing chemoattractant concentration. It has
      been recognized that the particular motility pattern employed by moving bacteria
      has a direct impact on the efficiency of chemotaxis. The linear theory of
      chemotaxis pioneered by de Gennes allows for calculation of the drift velocity in
      small gradients for bacteria with basic motility patterns. However, recent
      experimental data on several bacterial species highlighted the motility pattern
      where the almost straight runs of cells are interspersed with turning events
      leading to the reorientation of the cell swimming directions with two distinct
      angles following in strictly alternating order. In this manuscript we generalize
      the linear theory of chemotaxis to calculate the chemotactic drift speed for the
      motility pattern of bacteria with two turning angles. By using the experimental
      data on motility parameters of V. alginolyticus bacteria we can use our theory to
      relate the efficiency of chemotaxis and the size of bacterial cell body. The
      results of this work can have a straightforward extension to address most general
      motility patterns with alternating angles, speeds and durations of runs.

PMID- 29351337
TI  - A portable prototype magnetometer to differentiate ischemic and non-ischemic
      heart disease in patients with chest pain.
AB  - BACKGROUND: Magnetocardiography (MCG) is a non-invasive technique used to measure
      and map cardiac magnetic fields. We describe the predictive performance of a
      portable prototype magnetometer designed for use in acute and routine clinical
      settings. We assessed the predictive ability of the measurements derived from the
      magnetometer for the ruling-out of healthy subjects and patients whose chest pain
      has a non-ischemic origin from those with ischemic heart disease (IHD). METHODS:
      MCG data were analyzed from a technical performance study, a pilot clinical
      study, and a young healthy reference group. Participants were grouped to enable
      differentiation of those with IHD versus non-IHD versus controls: Group A (70 IHD
      patients); Group B (69 controls); Group C (37 young healthy volunteers). Scans
      were recorded in an unshielded room. Between-group differences were explored
      using analysis of variance. The ability of 10 candidate MCG predictors to predict
      normal/abnormal cases was analyzed using logistic regression. Predictive
      performance was internally validated using repeated five-fold cross-validation.
      RESULTS: Three MCG predictors showed a significant difference between patients
      and age-matched controls (P<0.001); eight predictors showed a significant
      difference between patients and young healthy volunteers (P<0.001). Logistic
      regression comparing patients with controls yielded a specificity of 35.0%,
      sensitivity of 95.4%, and negative predictive value for the ruling-out of IHD of
      97.8% (area under the curve 0.78). CONCLUSION: This analysis represents a
      preliminary indication that the portable magnetometer can help rule-out healthy
      subjects and patients whose chest pain has a non-ischemic origin from those with
      IHD.

PMID- 29351338
TI  - Stockouts of HIV commodities in public health facilities in Kinshasa: Barriers to
      end HIV.
AB  - Stockouts of HIV commodities increase the risk of treatment interruption,
      antiretroviral resistance, treatment failure, morbidity and mortality. The study
      objective was to assess the magnitude and duration of stockouts of HIV medicines
      and diagnostic tests in public facilities in Kinshasa, Democratic Republic of the
      Congo. This was a cross-sectional survey involving visits to facilities and
      warehouses in April and May 2015. All zonal warehouses, all public facilities
      with more than 200 patients on antiretroviral treatment (ART) (high-burden
      facilities) and a purposive sample of facilities with 200 or fewer patients (low
      burden facilities) in Kinshasa were selected. We focused on three adult ART
      formulations, cotrimoxazole tablets, and HIV diagnostic tests. Availability of
      items was determined by physical check, while stockout duration until the day of
      the survey visit was verified with stock cards. In case of ART stockouts, we
      asked the pharmacist in charge what the facility coping strategy was for patients
      needing those medicines. The study included 28 high-burden facilities and 64 low
      burden facilities, together serving around 22000 ART patients. During the study
      period, a national shortage of the newly introduced first-line regimen Tenofovir
      Lamivudine-Efavirenz resulted in stockouts of this regimen in 56% of high-burden
      and 43% of low-burden facilities, lasting a median of 36 (interquartile range 29
      90) and 44 days (interquartile range 24-90) until the day of the survey visit,
      respectively. Each of the other investigated commodities were found out of stock
      in at least two low-burden and two high-burden facilities. In 30/41 (73%) of
      stockout cases, the commodity was absent at the facility but present at the
      upstream warehouse. In 30/57 (54%) of ART stockout cases, patients did not
      receive any medicines. In some cases, patients were switched to different ART
      formulations or regimens. Stockouts of HIV commodities were common in the visited
      facilities. Introduction of new ART regimens needs additional planning.

PMID- 29351339
TI  - Brain functional BOLD perturbation modelling for forward fMRI and inverse
      mapping.
AB  - PURPOSE: To computationally separate dynamic brain functional BOLD responses from
      static background in a brain functional activity for forward fMRI signal analysis
      and inverse mapping. METHODS: A brain functional activity is represented in terms
      of magnetic source by a perturbation model: chi = chi0 +deltachi, with deltachi
      for BOLD magnetic perturbations and chi0 for background. A brain fMRI experiment
      produces a timeseries of complex-valued images (T2* images), whereby we extract
      the BOLD phase signals (denoted by deltaP) by a complex division. By solving an
      inverse problem, we reconstruct the BOLD deltachi dataset from the deltaP
      dataset, and the brain chi distribution from a (unwrapped) T2* phase image. Given
      a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal
      correlation analysis. RESULTS: Through a high-field (7T) and high-resolution
      (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD
      perturbation model for fMRI phase signal separation (P + deltaP) and
      reconstructing intrinsic brain magnetic source (chi and deltachi). We also
      provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in
      support of single-subject fMRI study. Our experiments show that the deltachi
      depicted functional map reveals bidirectional BOLD chi perturbations during the
      task performance. CONCLUSIONS: The BOLD perturbation model allows us to separate
      fMRI phase signal (by complex division) and to perform inverse mapping for pure
      BOLD deltachi reconstruction for intrinsic functional chi mapping. The full brain
      chi reconstruction (from unwrapped fMRI phase) provides a new brain tissue image
      that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD
      deltachi response through an automatic function/structure co-localization.

PMID- 29351340
TI  - Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail
      suspension-induced skeletal muscle atrophy.
AB  - BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine. Whether systemic IL
      6 affects atrogene expression and disuse-induced skeletal muscle atrophy is
      unclear. METHODS: Tail-suspended mice were used as a disuse-induced muscle
      atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy
      beta-methylbutyrate (HMB) and vitamin D to the mice and examined the effects on
      atrogene expression and muscle atrophy. RESULTS: Serum IL-6 levels were elevated
      in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1)
      expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL
      6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus
      muscle, and ameliorated atrophy in the mice. CONCLUSION: Systemic IL-6 affects
      MuRF1 expression and disuse-induced muscle atrophy.

PMID- 29351341
TI  - Labeling for Big Data in radiation oncology: The Radiation Oncology Structures
      ontology.
AB  - PURPOSE: Leveraging Electronic Health Records (EHR) and Oncology Information
      Systems (OIS) has great potential to generate hypotheses for cancer treatment,
      since they directly provide medical data on a large scale. In order to gather a
      significant amount of patients with a high level of clinical details, multicenter
      studies are necessary. A challenge in creating high quality Big Data studies
      involving several treatment centers is the lack of semantic interoperability
      between data sources. We present the ontology we developed to address this issue.
      METHODS: Radiation Oncology anatomical and target volumes were categorized in
      anatomical and treatment planning classes. International delineation guidelines
      specific to radiation oncology were used for lymph nodes areas and target
      volumes. Hierarchical classes were created to generate The Radiation Oncology
      Structures (ROS) Ontology. The ROS was then applied to the data from our
      institution. RESULTS: Four hundred and seventeen classes were created with a
      maximum of 14 children classes (average = 5). The ontology was then converted
      into a Web Ontology Language (.owl) format and made available online on Bioportal
      and GitHub under an Apache 2.0 License. We extracted all structures delineated in
      our department since the opening in 2001. 20,758 structures were exported from
      our "record-and-verify" system, demonstrating a significant heterogeneity within
      a single center. All structures were matched to the ROS ontology before
      integration into our clinical data warehouse (CDW). CONCLUSION: In this study we
      describe a new ontology, specific to radiation oncology, that reports all
      anatomical and treatment planning structures that can be delineated. This
      ontology will be used to integrate dosimetric data in the Assistance Publique
      Hopitaux de Paris CDW that stores data from 6.5 million patients (as of February
      2017).

PMID- 29351343
TI  - Minority race and male sex as risk factors for non-beneficial gastrostomy tube
      placements after stroke.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are widely used for
      enteral feeding after stroke; however, PEG tubes placed in patients in whom death
      is imminent are considered non-beneficial. AIM: We sought to determine whether
      placement of non-beneficial PEG tubes differs by race and sex. DESIGN AND
      SETTING/PARTICIPANTS: In this retrospective cohort study, inpatient admissions
      for stroke patients who underwent palliative/withdrawal of care, were discharged
      to hospice, or died during the hospitalization, were identified from the
      Nationwide Inpatient Sample between 2007 and 2011. Logistic regression was used
      to evaluate the association between race and sex with PEG placement. RESULTS: Of
      36,109 stroke admissions who underwent palliative/withdrawal of care, were
      discharge to hospice, or experienced in-hospital death, a PEG was placed in 2,258
      (6.3%). Among PEG recipients 41.1% were of a race other than white, while only
      22.0% of patients without PEG were of a minority race (p<0.001). The proportion
      of men was higher among those with compared to without a PEG tube (50.0% vs.
      39.2%, p<0.001). Minority race was associated with PEG placement compared to
      whites (OR 1.75, 95% CI 1.57-1.96), and men had 1.27 times higher odds of PEG
      compared to women (95% CI 1.16-1.40). Racial differences were most pronounced
      among women: ethnic/racial minority women had over 2-fold higher odds of a PEG
      compared to their white counterparts (OR 2.09, 95% CI 1.81-2.41), while male
      ethnic/racial minority patients had 1.44 increased odds of a PEG when compared to
      white men (95% CI 1.24-1.67, p-value for interaction <0.001). CONCLUSION:
      Minority race and male sex are risk factors for non-beneficial PEG tube
      placements after stroke.

PMID- 29351344
TI  - The morphing of geographical features by Fourier transformation.
AB  - This paper presents a morphing model of vector geographical data based on Fourier
      transformation. This model involves three main steps. They are conversion from
      vector data to Fourier series, generation of intermediate function by combination
      of the two Fourier series concerning a large scale and a small scale, and reverse
      conversion from combination function to vector data. By mirror processing, the
      model can also be used for morphing of linear features. Experimental results show
      that this method is sensitive to scale variations and it can be used for vector
      map features' continuous scale transformation. The efficiency of this model is
      linearly related to the point number of shape boundary and the interceptive value
      n of Fourier expansion. The effect of morphing by Fourier transformation is
      plausible and the efficiency of the algorithm is acceptable.

PMID- 29351345
TI  - To IMPRES or to EXPRES? Exploiting comparative judgments to measure and visualize
      implicit and explicit preferences.
AB  - We introduce an adaptation of the affect misattribution procedure (AMP), called
      the implicit preference scale (IMPRES). Participants who complete the IMPRES
      indicate their preference for one of two, simultaneously presented Chinese
      ideographs. Each ideograph is preceded by a briefly presented prime stimulus that
      is irrelevant to the task. Participants are hypothesized to prefer the ideograph
      that is preceded by the prime they prefer. In the present research, the IMPRES
      was designed to capture racial attitudes (preferences for white versus black
      faces) and age-related attitudes (preferences for young versus old faces).
      Results suggest that (a) the reliability of the IMPRES is similar (or even
      better) than the reliability of the AMP and (b) that the IMPRES and the AMP
      correlate significantly. However, neither the AMP nor the IMPRES were found to
      predict attitude-related outcome behavior (i.e., the preparedness to donate money
      to a charity benefiting ethnic minorities vs. the elderly). Further research is
      thus necessary to establish the validity of the IMPRES. Finally, we demonstrated
      that, unlike the AMP, the IMPRES allows for an in-depth assessment of
      unanticipated response patterns and/or extreme observations using
      multidimensional scaling algorithms.

PMID- 29351342
TI  - A homozygous missense variant in VWA2, encoding an interactor of the Fraser
      complex, in a patient with vesicoureteral reflux.
AB  - Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common
      cause (40-50%) of chronic kidney disease (CKD) in children. About 40 monogenic
      causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases
      can be explained by mutations in these 40 genes. To identify additional monogenic
      causes of CAKUT, we performed whole exome sequencing (WES) and homozygosity
      mapping (HM) in a patient with CAKUT from Indian origin and consanguineous
      descent. We identified a homozygous missense mutation (c.1336C>T, p.Arg446Cys) in
      the gene Von Willebrand factor A domain containing 2 (VWA2). With
      immunohistochemistry studies on kidneys of newborn (P1) mice, we show that Vwa2
      and Fraser extracellular matrix complex subunit 1 (Fras1) co-localize in the
      nephrogenic zone of the renal cortex. We identified a pronounced expression of
      Vwa2 in the basement membrane of the ureteric bud (UB) and derivatives of the
      metanephric mesenchyme (MM). By applying in vitro assays, we demonstrate that the
      Arg446Cys mutation decreases translocation of monomeric VWA2 protein and
      increases translocation of aggregated VWA2 protein into the extracellular space.
      This is potentially due to the additional, unpaired cysteine residue in the
      mutated protein that is used for intermolecular disulfide bond formation. VWA2 is
      a known, direct interactor of FRAS1 of the Fraser-Complex (FC). FC-encoding genes
      and interacting proteins have previously been implicated in the pathogenesis of
      syndromic and/or isolated CAKUT phenotypes in humans. VWA2 therefore constitutes
      a very strong candidate in the search for novel CAKUT-causing genes. Our results
      from in vitro experiments indicate a dose-dependent neomorphic effect of the
      Arg446Cys homozygous mutation in VWA2.

PMID- 29351347
TI  - Correction: Nitrogen uptake and assimilation in proliferating embryogenic
      cultures of Norway spruce-Investigating the specific role of glutamine.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0181785.].

PMID- 29351346
TI  - The Congenital Heart Disease Genetic Network Study: Cohort description.
AB  - The Pediatric Cardiac Genomics Consortium (PCGC) designed the Congenital Heart
      Disease Genetic Network Study to provide phenotype and genotype data for a large
      congenital heart defects (CHDs) cohort. This article describes the PCGC cohort,
      overall and by major types of CHDs (e.g., conotruncal defects) and subtypes of
      conotrucal heart defects (e.g., tetralogy of Fallot) and left ventricular outflow
      tract obstructions (e.g., hypoplastic left heart syndrome). Cases with CHDs were
      recruited through ten sites, 2010-2014. Information on cases (N = 9,727) and
      their parents was collected through interviews and medical record abstraction.
      Four case characteristics, eleven parental characteristics, and thirteen parent
      reported neurodevelopment outcomes were summarized using counts and frequencies
      and compared across CHD types and subtypes. Eleven percent of cases had a genetic
      diagnosis. Among cases without a genetic diagnosis, the majority had conotruncal
      heart defects (40%) or left ventricular outflow tract obstruction (21%). Across
      CHD types, there were significant differences (p<0.05) in the distribution of all
      four case characteristics (e.g., sex), four parental characteristics (e.g.,
      maternal pregestational diabetes), and five neurodevelopmental outcomes (e.g.,
      learning disabilities). Several characteristics (e.g., sex) were also
      significantly different across CHD subtypes. The PCGC cohort is one of the
      largest CHD cohorts available for the study of genetic determinants of risk and
      outcomes. The majority of cases do not have a genetic diagnosis. This description
      of the PCGC cohort, including differences across CHD types and subtypes, provides
      a reference work for investigators who are interested in collaborating with or
      using publically available resources from the PCGC.

PMID- 29351349
TI  - Survey research with a random digit dial national mobile phone sample in Ghana:
      Methods and sample quality.
AB  - INTRODUCTION: Generating a nationally representative sample in low and middle
      income countries typically requires resource-intensive household level sampling
      with door-to-door data collection. High mobile phone penetration rates in
      developing countries provide new opportunities for alternative sampling and data
      collection methods, but there is limited information about response rates and
      sample biases in coverage and nonresponse using these methods. We utilized data
      from an interactive voice response, random-digit dial, national mobile phone
      survey in Ghana to calculate standardized response rates and assess
      representativeness of the obtained sample. MATERIALS AND METHODS: The survey
      methodology was piloted in two rounds of data collection. The final survey
      included 18 demographic, media exposure, and health behavior questions. Call
      outcomes and response rates were calculated according to the American Association
      of Public Opinion Research guidelines. Sample characteristics, productivity, and
      costs per interview were calculated. Representativeness was assessed by comparing
      data to the Ghana Demographic and Health Survey and the National Population and
      Housing Census. RESULTS: The survey was fielded during a 27-day period in
      February-March 2017. There were 9,469 completed interviews and 3,547 partial
      interviews. Response, cooperation, refusal, and contact rates were 31%, 81%, 7%,
      and 39% respectively. Twenty-three calls were dialed to produce an eligible
      contact: nonresponse was substantial due to the automated calling system and
      dialing of many unassigned or non-working numbers. Younger, urban, better
      educated, and male respondents were overrepresented in the sample. CONCLUSIONS:
      The innovative mobile phone data collection methodology yielded a large sample in
      a relatively short period. Response rates were comparable to other surveys,
      although substantial coverage bias resulted from fewer women, rural, and older
      residents completing the mobile phone survey in comparison to household surveys.
      Random digit dialing of mobile phones offers promise for future data collection
      in Ghana and may be suitable for other developing countries.

PMID- 29351348
TI  - Interactions of 2'-O-methyl oligoribonucleotides with the RNA models of the 30S
      subunit A-site.
AB  - Synthetic oligonucleotides targeting functional regions of the prokaryotic rRNA
      could be promising antimicrobial agents. Indeed, such oligonucleotides were
      proven to inhibit bacterial growth. 2'-O-methylated (2'-O-Me)
      oligoribonucleotides with a sequence complementary to the decoding site in 16S
      rRNA were reported as inhibitors of bacterial translation. However, the binding
      mode and structures of the formed complexes, as well as the level of selectivity
      of the oligonucleotides between the prokaryotic and eukaryotic target, were not
      determined. We have analyzed three 2'-O-Me oligoribonucleotides designed to
      hybridize with the models of the prokaryotic rRNA containing two neighboring
      aminoglycoside binding pockets. One pocket is the paromomycin/kanamycin binding
      site corresponding to the decoding site in the small ribosomal subunit and the
      other one is the close-by hygromycin B binding site whose dynamics has not been
      previously reported. Molecular dynamics (MD) simulations, as well as isothermal
      titration calorimetry, gel electrophoresis and spectroscopic studies have shown
      that the eukaryotic rRNA model is less conformationally stable (in terms of
      hydrogen bonds and stacking interactions) than the corresponding prokaryotic one.
      In MD simulations of the eukaryotic construct, the nucleotide U1498, which plays
      an important role in correct positioning of mRNA during translation, is flexible
      and spontaneously flips out into the solvent. In solution studies, the 2'-O-Me
      oligoribonucleotides did not interact with the double stranded rRNA models but
      all formed stable complexes with the single-stranded prokaryotic target. 2'-O-Me
      oligoribonucleotides with one and two mismatches bound less tightly to the
      eukaryotic target. This shows that at least three mismatches between the 2'-O-Me
      oligoribonucleotide and eukaryotic rRNA are required to ensure target
      selectivity. The results also suggest that, in the ribosome environment, the
      strand invasion is the preferred binding mode of 2'-O-Me oligoribonucleotides
      targeting the aminoglycoside binding sites in 16S rRNA.

PMID- 29351350
TI  - Visualized analysis of developing trends and hot topics in natural disaster
      research.
AB  - This study visualized and analyzed the developing trends and hot topics in
      natural disaster research. 19694 natural disaster-related articles (January 1900
      to June 2015) are indexed in the Web of Science database. The first step in this
      study is using complex networks to visualize and analyze these articles.
      CiteSpace and Gephi were employed to generate a countries collaboration network
      and a disciplines collaboration network, and then attached hot topics to
      countries and disciplines, respectively. The results show that USA, China, and
      Italy are the three major contributors to natural disaster research. "Prediction
      model", "social vulnerability", and "landslide inventory map" are three hot
      topics in recent years. They have attracted attention not only from large
      countries like China but also from small countries like Panama and Turkey.
      Comparing two hybrid networks provides details of natural disaster research.
      Scientists from USA and China use image data to research earthquakes. Indonesia
      and Germany collaboratively study tsunamis in the Indian Ocean. However,
      Indonesian studies focus on modeling and simulations, while German research
      focuses on early warning technology. This study also introduces an activity index
      (AI) and an attractive index (AAI) to generate time evolution trajectories of
      some major countries from 2000 to 2013 and evaluate their trends and performance.
      Four patterns of evolution are visible during this 14-year period. China and
      India show steadily rising contributions and impacts, USA and England show
      relatively decreasing research efforts and impacts, Japan and Australia show
      fluctuating activities and stable attraction, and Spain and Germany show
      fluctuating activities and increasing impacts.

PMID- 29351351
TI  - Comparing performance on the MNREAD iPad application with the MNREAD acuity
      chart.
AB  - Our purpose was to compare reading performance measured with the MNREAD Acuity
      Chart and an iPad application (app) version of the same test for both normally
      sighted and low-vision participants. Our methods included 165 participants with
      normal vision and 43 participants with low vision tested on the standard printed
      MNREAD and on the iPad app version of the test. Maximum Reading Speed, Critical
      Print Size, Reading Acuity, and Reading Accessibility Index were compared using
      linear mixed-effects models to identify any potential differences in test
      performance between the printed chart and the iPad app. Our results showed the
      following: For normal vision, chart and iPad yield similar estimates of Critical
      Print Size and Reading Acuity. The iPad provides significantly slower estimates
      of Maximum Reading Speed than the chart, with a greater difference for faster
      readers. The difference was on average 3% at 100 words per minute (wpm), 6% at
      150 wpm, 9% at 200 wpm, and 12% at 250 wpm. For low vision, Maximum Reading
      Speed, Reading Accessibility Index, and Critical Print Size are equivalent on the
      iPad and chart. Only the Reading Acuity is significantly smaller (I. E., better)
      when measured on the digital version of the test, but by only 0.03 logMAR (p =
      0.013). Our conclusions were that, overall, MNREAD parameters measured with the
      printed chart and the iPad app are very similar. The difference found in Maximum
      Reading Speed for the normally sighted participants can be explained by
      differences in the method for timing the reading trials.

PMID- 29351352
TI  - The retinal locus of fixation in simulations of progressing central scotomas.
AB  - Patients with central scotoma use a preferred retinal locus (PRL) of fixation to
      perform visual tasks. Some of the conditions that cause central scotoma are
      progressive, and as a consequence, the PRL needs to be adjusted throughout the
      progression. The present study investigates the peripheral locus of fixation in
      subjects under a simulation of progressive central scotoma. Five normally sighted
      subjects participated in the study. A foveally centered mask of varying size was
      presented to simulate the scotoma. Initially, subjects developed a peripheral
      locus of fixation under simulation of a 6 degrees  scotoma, which was used as a
      baseline. The progression was simulated in two separate conditions: a gradual
      progression and an abrupt progression. In the gradual progression, the diameter
      of the scotoma increased by a fixed amount of either 1 degrees  or 2 degrees  of
      visual angle, thus scotomas of 8 degrees , 10 degrees , and 11 degrees  of visual
      angle were simulated. In the abrupt progression, the diameter was adjusted
      individually to span the area of the visual field used by the current peripheral
      locus of fixation. Subjects located the peripheral locus of fixation along the
      same meridian under simulation of scotoma progression. Furthermore, no
      differences between the fixation stability of the baseline locus of fixation and
      the incremental progression locus of fixation were found whereas, in abrupt
      progression, the fixation stability decreased significantly. These results
      provide first insight into fixation behavior in a progressive scotoma and may
      contribute to the development of training tools for patients with progressive
      central maculopathies.

PMID- 29351353
TI  - The Contributions of Phonological Awareness, Alphabet Knowledge, and Letter
      Writing to Name Writing in Children With Specific Language Impairment and
      Typically Developing Children.
AB  - Purpose: Name writing is one aspect of emergent writing that has been used to
      understand emergent literacy development. Name-writing skills and the
      relationship of name writing to other emergent literacy skills have not been
      studied extensively in children with specific language impairment (SLI). Children
      with SLI consistently demonstrate delays in phonological awareness (PA), alphabet
      knowledge (AK), print awareness, and emergent writing. The purpose of this study
      was to examine the contributions of PA, AK, and letter writing to name writing in
      children with SLI and typically developing (TD) children. Method: Participants
      were 65 children (22 SLI, 43 TD) with an average age of 53 months. Participants
      completed the Assessment of Literacy and Language (Lombardino, Lieberman, &
      Brown, 2005), a letter-writing task, and a name-writing task. Results: Data were
      analyzed using correlation and mediation modeling. Mediation modeling, a more
      sophisticated analysis, revealed that PA, AK, and letter writing, in serial, were
      mediating variables for language status on name writing. Conclusion: Phonemic
      awareness, AK, and letter writing help to explain the relationship between
      language status and name writing. These skills should be integrated during
      treatment, using a horizontal approach with developmentally appropriate
      activities, particularly for children with SLI.

PMID- 29351354
TI  - The Effects of Intensive Speech Treatment on Conversational Intelligibility in
      Spanish Speakers With Parkinson's Disease.
AB  - Purpose: The purpose of this study was to examine the effects of intensive speech
      treatment on the conversational intelligibility of Castilian Spanish speakers
      with Parkinson's disease (PD), as well as on the speakers' self-perceptions of
      disability. Method: Fifteen speakers with a medical diagnosis of PD participated
      in this study. Speech recordings were completed twice before treatment,
      immediately posttreatment, and at a 1-month follow-up session. Conversational
      intelligibility was assessed in 2 ways-transcription accuracy scores and
      intelligibility ratings on a 9-point Likert scale. The Voice Handicap Index
      (Nunez-Batalla et al., 2007) was administered as a measure of self-perceived
      disability. Results: Group data revealed that transcription accuracy and median
      ease-of-understanding ratings increased significantly immediately posttreatment,
      with gains maintained at the 1-month follow-up. The functional subscale of the
      Voice Handicap Index decreased significantly posttreatment, suggesting a decrease
      in perceived communication disability after speech treatment. Conclusion: These
      findings support the implementation of intensive voice treatment to improve
      conversational intelligibility in Spanish speakers with PD with dysarthria as
      well as to improve the speakers' perception of their daily communicative
      capabilities. Clinical and theoretical considerations are discussed.

PMID- 29351355
TI  - Physicians Join Frontline Efforts to Curb Gun Injuries, Deaths.

PMID- 29351356
TI  - EphA2/Ephrin-A1 Mediate Corneal Epithelial Cell Compartmentalization via ADAM10
      Regulation of EGFR Signaling.
AB  - Purpose: Progenitor cells of the limbal epithelium reside in a discrete area
      peripheral to the more differentiated corneal epithelium and maintain tissue
      homeostasis. What regulates the limbal-corneal epithelial boundary is a major
      unanswered question. Ephrin-A1 ligand is enriched in the limbal epithelium,
      whereas EphA2 receptor is concentrated in the corneal epithelium. This reciprocal
      pattern led us to assess the role of ephrin-A1 and EphA2 in limbal-corneal
      epithelial boundary organization. Methods: EphA2-expressing corneal epithelial
      cells engineered to express ephrin-A1 were used to study boundary formation in
      vitro in a manner that mimicked the relative abundance of these juxtamembrane
      signaling proteins in the limbal and corneal epithelium in vivo. Interaction of
      these two distinct cell populations following initial seeding into discrete
      culture compartments was assessed by live cell imaging. Immunofluoresence and
      immunoblotting was used to evaluate the contribution of downstream growth factor
      signaling and cell-cell adhesion systems to boundary formation at sites of
      heterotypic contact between ephrin-A1 and EphA2 expressing cells. Results: Ephrin
      A1-expressing cells impeded and reversed the migration of EphA2-expressing
      corneal epithelial cells upon heterotypic contact formation leading to
      coordinated migration of the two cell populations in the direction of an ephrin
      A1-expressing leading front. Genetic silencing and pharmacologic inhibitor
      studies demonstrated that the ability of ephrin-A1 to direct migration of EphA2
      expressing cells depended on an a disintegrin and metalloproteinase domain
      containing protein 10 (ADAM10) and epidermal growth factor receptor (EGFR)
      signaling pathway that limited E-cadherin-mediated adhesion at heterotypic
      boundaries. Conclusions: Ephrin-A1/EphA2 signaling complexes play a key role in
      limbal-corneal epithelial compartmentalization and the response of these tissues
      to injury.

PMID- 29351357
TI  - Changes in Axial Length and Progression of Visual Field Damage in Glaucoma.
AB  - Purpose: To investigate the relationship between axial length (AL) elongation and
      progression of primary open-angle glaucoma (POAG). Methods: AL was measured twice
      over a 5.1 +/- 0.76 (mean +/- standard deviation: SD) year period in 125 eyes of
      72 patients with POAG. The eyes were divided into not long (AL < 26 mm, 80 eyes)
      and long (>26 mm, 45 eyes) groups. During this period, patients' visual fields
      (VFs) were measured with the Humphrey Field Analyzer 12.4 +/- 7.5 times and
      intraocular pressure (IOP) was measured with Goldmann applanation tonometry 27.0
      +/- 7.5 times. The relationship between the mean total deviation (mTD)
      progression rates in the whole field and superior and inferior hemifield, as well
      as in 10 VF sectors, and the variables of age, mean IOP, SD of IOP, AL,
      difference in AL (?AL), and mTD value at baseline was examined. Results: There
      was a significant difference between AL at baseline and AL at repeat measurement
      (P < 0.0001). ?AL was 0.035 +/- 0.10 mm. An increase in ?AL was significantly
      related to AL at baseline (P = 0.027), but not to age, mean IOP, and SD of IOP.
      ?AL was related to the progression of mTD in the inferior hemifield (slower mTD
      progression was associated with increased ?AL), but not in the whole field or
      superior hemifield. Increased ?AL was related to slower progression rates in 2 of
      10 sectors, both in the inferior hemifield. Conclusions: The main finding was
      that an increase in AL was significantly related to slower VF progression in the
      inferior hemifield.

PMID- 29351358
TI  - Microfluidics-Based Subretinal Chemical Neuromodulation of Photoreceptor
      Degenerated Retinas.
AB  - Purpose: Retinal prostheses can restore rudimentary vision in cases of
      photoreceptor degeneration through electrical stimulation, but face difficulties
      achieving high spatial resolution because electrical current is an inherently
      unnatural stimulus. We investigated the therapeutic feasibility of using
      patterned delivery of the glutamate neurotransmitter, a primary agent of natural
      synaptic communication of the retina, as a biomimetic chemical alternative to
      electrical current for neuromodulation of photoreceptor degenerate retina.
      Methods: We injected small quantities of the neurotransmitter glutamate into the
      subretina of 20 explanted photoreceptor degenerated S334ter-3 rat retinas using
      glass micropipettes and a prototype multiport microfluidic device to accomplish
      single- and multisite stimulation in vitro. The effects of chemical stimulation
      were characterized by recording neural responses from retinal ganglion cells
      (RGCs) using a multielectrode array. Results: Subretinally injected exogenous
      glutamate activates RGCs, despite the substantial anatomic and physiologic
      changes caused by retinal remodeling, eliciting robust neural responses. The
      presence of excitatory and inhibitory RGC responses provides evidence that
      exogenous glutamate differentially activated neurons presynaptic to RGCs, likely
      inner retinal neurons belonging to the OFF and ON pathways. We also demonstrate
      that glutamate injections can evoke focal RGC responses with spatial resolutions
      comparable to or better than current generation electrical prostheses and, when
      applied at multiple sites simultaneously with the multiport microfluidic device,
      can produce spatially patterned neural responses. Conclusions: These significant
      results establish that chemical stimulation of degenerated retinas with
      neurotransmitters is an effective neuromodulation strategy with the potential of
      restoring high-resolution visual perception in patients rendered blind through
      photoreceptor degeneration.

PMID- 29351360
TI  - Collection of Wet-Origin Footwear Impressions on Various Surfaces Using an
      Electrostatic Dust Print Lifter.
AB  - Electrostatic dust print lift method is known to be able to recover only dry
      origin footwear impression. However, the wet-origin footwear impression could
      also be recovered using this method. As the amount of dust accumulated before
      deposition of the wet-origin footwear impression increased, the intensity of the
      footwear impression lifted with this method became stronger. If the footwear
      impression is not affected by moisture after it is made, the 28-h old wet-origin
      footwear impression could be recovered using this method. The intensity of the
      lifted footwear impression did not decrease significantly even when the number of
      sequential steps increased as long as the shoe sole is wet. However, when the
      moisture on the shoe sole depleted, the intensity of the footwear impression
      decreased sharply. This method has the advantage of being able to enhance the
      footwear impression without being affected by the footwear impressions deposited
      in the past.

PMID- 29351361
TI  - Pathways of nitric oxide metabolism and operation of phytoglobins in legume
      nodules: missing links and future directions.
AB  - The interaction between legumes and rhizobia leads to the establishment of a
      beneficial symbiotic relationship. Recent advances in legume - rhizobium
      symbiosis revealed that various reactive oxygen and nitrogen species including
      nitric oxide (NO) play important roles during this process. Nodule development
      occurs with a transition from a normoxic environment during the establishment of
      symbiosis to a microoxic environment in functional nodules. Such oxygen dynamics
      are required for activation and repression of various NO production and
      scavenging pathways. Both the plant and bacterial partners participate in the
      synthesis and degradation of NO. However, the pathways of NO production and
      degradation as well as their cross-talk and involvement in the metabolism are
      still a matter of debate. The plant-originated reductive pathways are known to
      contribute to the NO production in nodules under hypoxic conditions. Non
      symbiotic hemoglobin (phytoglobin) (Pgb) possesses high NO oxygenation capacity,
      buffers and scavenges NO. Its operation, through a respiratory cycle called Pgb
      NO cycle, leads to the maintenance of redox and energy balance in nodules. The
      role of Pgb/NO cycle under fluctuating NO production from soil needs further
      investigation for complete understanding of NO regulatory mechanism governing
      nodule development to attain optimal food security under changing environment.

PMID- 29351359
TI  - CYR61/CCN1 Regulates Sclerostin Levels and Bone Maintenance.
AB  - CYR61/CCN1 is a matricellular protein that resides in the extracellular matrix,
      but serves regulatory rather than structural roles. CYR61/CCN1 is found in
      mineralized tissues and has been shown to influence bone healing in vivo and
      osteogenic differentiation in vitro. In this study we generated Cyr61 bone
      specific knockout mice to examine the physiological role of CYR61/CCN1 in bone
      development and maintenance in vivo. Extensive analysis of Cyr61 conditional
      knockout mice showed a significant decrease in both trabecular and cortical bone
      mass as compared to WT littermates. Our data suggest that CYR61/CCN1 exerts its
      effects on mature osteoblast/osteocyte function to modulate bone mass.
      Specifically, changes were observed in osteocyte/osteoblast expression of RankL,
      VegfA, and Sost. The increase in RankL expression was correlated with a
      significant increase in osteoclast number; decreased VegfA expression was
      correlated with a significant decrease in bone vasculature; increased Sost
      expression was associated with decreased Wnt signaling, as revealed by decreased
      Axin2 expression and increased adiposity in the bone marrow. Although the
      decreased number of vascular elements in bone likely contributes to the low bone
      mass phenotype in Cyr61 conditional knockout mice, this cannot explain the
      observed increase in osteoclasts and the decrease in Wnt signaling. We conducted
      in vitro assays using UMR-106 osteosarcoma cells to explore the role CYR61/CCN1
      plays in modulating Sost mRNA and protein expression in osteocytes and
      osteoblasts. Overexpression of CYR61/CCN1 can suppress Sost expression in both
      control and Cyr61 knockout cells, and blocking Sost with siRNA can rescue Wnt
      responsiveness in Cyr61 knockout cells in vitro. Overall, our data suggest that
      CYR61/CCN1 modulates mature osteoblast and osteocyte function to regulate bone
      mass through angiogenic effects as well as by modulating Wnt signaling, at least
      in part through the Wnt antagonist Sost. (c) 2018 American Society for Bone and
      Mineral Research.

PMID- 29351362
TI  - Analysis of the Effect of Cyclophosphamide and Methotrexate on Chrysomya
      megacephala (Diptera: Calliphoridae).
AB  - Forensic entomotoxicology investigates the effects of chemical substances in the
      development of scavenger insects and the reflection on estimating the minimum
      postmortem interval (PMI). To evaluate the impact of the chemotherapeutic drugs
      cyclophosphamide (CF) and methotrexate (MTX) on the postembryonic development of
      Chrysomya megacephala, controlled experiments were performed by rearing the
      larvae on spiked minced beef with different concentrations of these drugs. The
      results indicated that CF significantly decreased their developmental rate up to
      28 h but had no significant effect on larval and adult sizes, survival rate, and
      sex ratio, whereas MTX decreased larval and adult sizes, survival rate, and there
      was a deviation in the expected sex ratio toward females in MTX-exposed larvae
      but had no significant impact on developmental rate. These negative interference
      factors should be considered in cases of suspected death of people that have
      undergone chemotherapy.

PMID- 29351363
TI  - Carers' experiences of home enteral feeding: A survey exploring medicines
      administration challenges and strategies.
AB  - WHAT IS KNOWN AND OBJECTIVES: The use of enteral tube feeding at home is becoming
      more widespread, with patients ranging in age and diseases. Dysphagia and
      swallowing difficulties can compromise nutritional intake and the administration
      of oral medications, affecting therapeutic outcomes negatively. Carers'
      experiences of medicines administration and medicines optimization have not been
      explored fully. The objectives of this study were to identify issues carers
      experience in medicines administration; the strategies they have developed to
      cope; and suggestions to improve the medicines administration process. METHODS:
      An online survey was promoted nationally; 42 carers completed it. Descriptive
      statistical analysis was applied, as well as thematic analysis of open-ended
      responses. Results were compared against the 4 principles of medicines
      optimization. RESULTS AND DISCUSSION: 93% of respondents administered medications
      with enteral feeding tubes, but only 62% had received advice from healthcare
      professionals and only 8% had received written information on how to do so.
      Responses identified 5 medicines administration issues experienced by carers; 4
      strategies they developed to cope; and 3 main areas of suggestions to improve
      medicines administration via enteral feeding at home. WHAT IS NEW AND CONCLUSION:
      The 4 principles of medicines optimization have not previously been applied to
      enteral feeding. We present a novel account of carers' experiences, for example
      coping with ill-suited formulations and a lack of training and support, which
      should inform better practice (Principle 1). Carers sometimes experience
      suboptimal choice of medicines (Principle 2). Carers' practices are not always
      well-informed and may affect therapeutic outcomes and safety (Principle 3). There
      is scope for improvement in carer training, education and support to better
      support medicines optimization (Principle 4).

PMID- 29351364
TI  - The Ethical Foundations of Risk Analysis.
AB  - In the field of risk analysis, the normative value systems underlying accepted
      methodology are rarely explicitly discussed. This perspective provides a critique
      of the various ethical frameworks that can be used in risk assessments and risk
      management decisions. The goal is to acknowledge philosophical weaknesses that
      should be considered and communicated in order to improve the public acceptance
      of the work of risk analysts.

PMID- 29351365
TI  - A novel technique for collateral interruption to maximize portal venous flow in
      pediatric liver transplantation.

PMID- 29351366
TI  - Living donor liver transplantation for hepatocellular carcinoma: To expand
      (beyond Milan) or downstage (to Milan)?

PMID- 29351367
TI  - Accurate understanding of infertility risk among families of adolescent males
      newly diagnosed with cancer.
AB  - OBJECTIVE: To examine patient and parent understanding of infertility risk
      (relative to oncologists' risk ratings) among adolescents newly diagnosed with
      cancer, and to identify background factors related to inaccurate
      reporting/estimating. METHODS: Male patients (N = 137; aged 13-21) and their
      parents completed self-report questionnaires. Those who reported a fertility
      related conversation with their provider (N = 102 adolescents, N = 74 parents)
      reported their infertility risk (ie, what oncologist had communicated) and all
      participants' estimated risk (ie, personal belief). Reports/estimates were
      compared with oncologists' ratings to assess relative accuracy, and regression
      analyses assessed potentially related background factors. RESULTS: Participants'
      agreement of their risk reports with the oncologist was poor (kappa = .079/.122
      for adolescents/parents), resulting in most adolescents (59.8%) and parents
      (58.7%) inaccurately reporting risk. Older adolescents were less likely to
      overreport risk (OR = 0.69; 95% CI, 0.49-0.97) and parents of sons with the
      highest Tanner stage were less likely to underreport (OR = 0.28; 95% CI, 0.08
      0.92). Risk estimates were also in poor agreement with oncologists' ratings among
      adolescents (kappa = .040) and parents (kappa = .088). Accordingly, incongruent
      estimates occurred in most adolescents (63.7%) and parents (62.2%), although all
      reported fertility-related conversations with their providers. CONCLUSIONS: Most
      adolescents and parents inaccurately reported infertility risk, and more poorly
      estimated risk. Research is needed to identify additional factors associated with
      accurate understanding of cancer-related infertility risk. Providers should be
      supported with user-friendly educational tools to promote awareness of
      infertility risk.

PMID- 29351368
TI  - Benefit finding and diurnal cortisol after prostate cancer: The mediating role of
      positive affect.
AB  - OBJECTIVE: Benefit finding (BF) has exhibited a salutary effect on psychological
      adjustment to cancer. However, few studies have examined its relationship with
      physiology or have examined BF in men with cancer. This study investigated
      whether BF is associated with hypothalamic-pituitary-adrenal axis activity (ie,
      diurnal salivary cortisol) in men treated for prostate cancer. Positive affect
      (PA) is proposed as a potential pathway linking BF to diurnal salivary cortisol.
      METHODS: A sample of 66 men treated for localized prostate cancer within the
      prior 2 years completed questionnaires and collected salivary cortisol 3 times
      per day over 3 consecutive days. Hierarchical linear modeling was used for
      estimating the effects of BF and PA on cortisol responses as measured by diurnal
      slope and area under the curve (AUCg). Confidence intervals for indirect effects
      were estimated using the Monte Carlo method for mediation testing. RESULTS: BF
      was significantly associated with diurnal cortisol slope, controlling for body
      mass index and age (B = -.12, P = .03), such that greater BF was associated with
      steeper cortisol slope. Analyses revealed that PA mediated the effect of BF on
      cortisol slope (Monte Carlo estimation 95% CI = -0.087, -0.001); negative affect
      did not mediate this relationship. BF was not significantly associated with AUCg.
      CONCLUSIONS: Deriving more benefit from one's experience with prostate cancer is
      associated with a healthier diurnal cortisol rhythm. Through its potential to
      enhance PA, the relationship of BF and physiological processes underscores the
      health relevant value of BF in prostate cancer survivors.

PMID- 29351369
TI  - Heparin but not tissue plasminogen activator improves outcomes in donation after
      circulatory death liver transplantation in a porcine model.
AB  - Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after
      circulatory death (DCD) liver transplantation and result in high morbidity and
      graft loss. Many DCD grafts are discarded out of fear for this complication. In
      theory, microvascular thrombi deposited during donor warm ischemia might be
      implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the
      administration of either heparin or the fibrinolytic drug tissue plasminogen
      activator (TPA) as means to improve DCD liver graft quality and potentially avoid
      ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided
      among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional
      perfusion; no pre-arrest heparinization but TPA given during regional perfusion;
      and pre-arrest heparinization but no TPA during regional perfusion. In liver
      tissue sampled 1 hour after CA, fibrin deposition was not detected, even when
      heparin was not given prior to arrest. Although it was not useful to prevent
      microvascular clot formation, pre-arrest heparin did offer cytoprotective effects
      during CA and beyond, reflected in improved flows during regional perfusion and
      better biochemical, functional, and histological parameters during
      posttransplantation follow-up. In conclusion, this study demonstrates the lack of
      impact of TPA use in porcine DCD liver transplantation and adds to the
      controversy over whether the use of TPA in human DCD liver transplantation really
      offers any protective effect. On the other hand, when it is administered prior to
      CA, heparin does offer anti-inflammatory and other cytoprotective effects that
      help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018
      AASLD.

PMID- 29351370
TI  - Avoid rejecting livers from donation after circulatory death donors based on
      donor age alone.

PMID- 29351371
TI  - Implementation of Standardized Clinical Processes for TPMT Testing in a Diverse
      Multidisciplinary Population: Challenges and Lessons Learned.
AB  - Although thiopurine S-methyltransferase (TPMT) genotyping to guide thiopurine
      dosing is common in the pediatric cancer population, limited data exist on TPMT
      testing implementation in diverse, multidisciplinary settings. We established
      TPMT testing (genotype and enzyme) with clinical decision support,
      provider/patient education, and pharmacist consultations in a tertiary medical
      center and collected data over 3 years. During this time, 834 patients underwent
      873 TPMT tests (147 (17%) genotype, 726 (83%) enzyme). TPMT tests were most
      commonly ordered for gastroenterology, rheumatology, dermatology, and
      hematology/oncology patients (661 of 834 patients (79.2%); 580 outpatient vs. 293
      inpatient; P < 0.0001). Thirty-nine patients had both genotype and enzyme tests
      (n = 2 discordant results). We observed significant differences between TPMT test
      use and characteristics in a diverse, multispecialty environment vs. a pediatric
      cancer setting, which led to unique implementation needs. As pharmacogenetic
      implementations expand, disseminating lessons learned in diverse, real-world
      environments will be important to support routine adoption.

PMID- 29351372
TI  - A Preclinical Population Pharmacokinetic Model for Anti-CD20/CD3 T-Cell-Dependent
      Bispecific Antibodies.
AB  - CD20 is a cell-surface receptor expressed by healthy and neoplastic B cells and
      is a well-established target for biologics used to treat B-cell malignancies.
      Pharmacokinetic (PK) and pharmacodynamic (PD) data for the anti-CD20/CD3 T-cell
      dependent bispecific antibody BTCT4465A were collected in transgenic mouse and
      nonhuman primate (NHP) studies. Pronounced nonlinearity in drug elimination was
      observed in the murine studies, and time-varying, nonlinear PK was observed in
      NHPs, where three empirical drug elimination terms were identified using a mixed
      effects modeling approach: i) a constant nonsaturable linear clearance term (7
      mL/day/kg); ii) a rapidly decaying time-varying, linear clearance term (t1/2  =
      1.6 h); and iii) a slowly decaying time-varying, nonlinear clearance term (t1/2 
      = 4.8 days). The two time-varying drug elimination terms approximately track with
      time scales of B-cell depletion and T-cell migration/expansion within the central
      blood compartment. The mixed-effects NHP model was scaled to human and
      prospective clinical simulations were generated.

PMID- 29351373
TI  - A Facile Space-Confined Solid-Phase Sulfurization Strategy for Growth of High
      Quality Ultrathin Molybdenum Disulfide Single Crystals.
AB  - Single-crystal transition metal dichalcogenides (TMDs) and TMD-based
      heterojunctions have recently attracted significant research and industrial
      interest owing to their intriguing optical and electrical properties. However,
      the lack of a simple, low-cost, environmentally friendly, synthetic method and a
      poor understanding of the growth mechanism post a huge challenge to implementing
      TMDs in practical applications. In this work, we developed a novel approach for
      direct formation of high-quality, monolayer and few-layer MoS2 single crystal
      domains via a single-step rapid thermal processing of a sandwiched reactor with
      sulfur and molybdenum (Mo) film in a confined reaction space. An all-solid-phase
      growth mechanism was proposed and experimentally/theoretically evidenced by
      analyzing the surface potential and morphology mapping. Compared with the
      conventional chemical vapor deposition approaches, our method involves no
      complicated gas-phase reactant transfer or reactions and requires very small
      amount of solid precursors [e.g., Mo (~3 MUg)], no carrier gas, no pretreatment
      of the precursor, no complex equipment design, thereby facilitating a simple, low
      cost, and environmentally friendly growth. Moreover, we examined the symmetry,
      defects, and stacking phase in as-grown MoS2 samples using simultaneous second
      harmonic-/sum-frequency-generation (SHG/SFG) imaging. For the first time, we
      observed that the SFG (peak intensity/position) polarization can be used as a
      sensitive probe to identify the orientation of TMDs' crystallographic axes.
      Furthermore, we fabricated ferroelectric programmable Schottky junction devices
      via local domain patterning using the as-grown, single-crystal monolayer MoS2,
      revealing their great potential in logic and optoelectronic applications. Our
      strategy thus provides a simple, low-cost, and scalable path toward a wide
      variety of TMD single crystal growth and novel functional device design.

PMID- 29351375
TI  - [Possibilities of using sodium hyaluronate in pharmaceutical and medical fields].
AB  - Sodium hyaluronate represents a contemporary biomaterial with broad use in
      different pharmaceutical and medical fields. It is a physiological
      glycosaminoglycan, which occurs primarily in the extracellular matrix, synovial
      fluid, cartilage, epidermis and vitreous body. It plays a critical role as a
      signalling molecule in immunological processes, cell motility and wound healing,
      and it possesses antioxidant activity. It is used in many fields of medicine if
      supplementation of hyaluronan is needed or in the cases of preventive and
      therapeutic interventions. Thanks to its moisturizing, regenerative and
      protective effects it is used in cosmetics as well.Key words: sodium hyaluronate
      hyaluronic acid hyaluronan derivatives of sodium hyaluronate dosage forms
      medicinal use.

PMID- 29351374
TI  - Fast Dynamic Docking Guided by Adaptive Electrostatic Bias: The MD-Binding
      Approach.
AB  - Engineering chemical entities to modify how pharmaceutical targets function, as
      it is done in drug design, requires a good understanding of molecular recognition
      and binding. In this context, the limitations of statically describing
      bimolecular recognition, as done in docking/scoring, call for insightful and
      efficient dynamical investigations. On the experimental side, the
      characterization of dynamical binding processes is still in its infancy. Thus,
      computer simulations, particularly molecular dynamics (MD), are compelled to play
      a prominent role, allowing a deeper comprehension of the binding process and its
      causes and thus a more informed compound selection, making more significant the
      computational contribution to drug discovery (Carlson, H. A. Curr. Opin. Chem.
      Biol. 2002, 6, 447-452). Unfortunately, MD-based approaches cannot yet describe
      complex events without incurring prohibitive time and computational costs. Here,
      we present a new method for fully and dynamically simulating drug-target-complex
      formations, tested against a real world and pharmaceutically relevant benchmark
      set. The method, based on an adaptive, electrostatics-inspired bias, envisions a
      campaign of trivially parallel short MD simulations and a strategy to identify a
      near native binding pose from the sampled configurations. At an affordable
      computational cost, this method provided predictions of good accuracy also when
      the starting protein conformation was different from that of the crystal complex,
      a known hurdle for traditional molecular docking (Lexa, K. W.; Carlson, H. A. Q.
      Rev. Biophys. 2012, 45, 301-343). Moreover, along the observed binding routes, it
      identified some key features also found by much more computationally expensive
      plain-MD simulations. Overall, this methodology represents significant progress
      in the description of binding phenomena.

PMID- 29351376
TI  - [Cholinesterase activity assays and their use in the diagnosis of various
      pathological states including poisoning by neurotoxic agents].
AB  - Cholinesterases are enzymes important for some nerve transmissions where the
      enzyme acetylcholinesterase plays a crucial role. The second enzyme,
      butyrylcholinesterase, is not necessary for the neurotransmission but it is
      involved in some detoxification reactions. A survey of literature, a discussion
      of diagnostic importance and the methods for an activity assay are presented in
      this review article. Liver failures, exposure to neurotoxic compounds, genetic
      dispositions are outlined here. In the field of assays, spectrophotometric,
      colorimetric and electrochemical tests are discussed.Key words:
      acetylcholinesterase butyrylcholinesterase poisoning liver function test
      pesticide nerve agent Alzheimer disease pathological state.

PMID- 29351377
TI  - [Specifics of some calcium salts in intravenous therapy of hypocalcemia and their
      further use].
AB  - Hypocalcemia is a serious condition which has a major impact on the transmission
      of nerve impulses, contraction and relaxation of muscles (including myocardial)
      and pathological secretion of some hormones. The basic causal treatment is the
      parenteral administration of calcium, namely calcium gluconate, calcium chloride
      or calcium gluceptate. Parenteral formulations of these compounds must meet
      pharmacopoeial requirements, including the aluminum content limit. Each of these
      molecules has its specific properties that predict their clinical use. In
      addition to hypocalcemia, they are used to influence a variety of other
      conditions, such as fluoride or oxalic acid poisoning, decreased myocardial
      contractility caused by overdose of calcium intake blockers or beta blockers.
      They are also used as part of parenteral nutrition AIO or as an ancillary
      treatment for acute allergic conditions, itchy dermatitis, weeping and
      generalized eczema, continuous renal replacement therapy, seizure convulsion,
      laryngospasm, bronchospasm and altered mental status. The role of calcium
      replacement in septic patients remains unclear and requires further study.
      Although it may appear that calcium chloride infusion solutions provide greater
      and more highly ionized amounts of calcium, gluconate salts are preferred due to
      considerably less irritation of the vessel wall and better compatibility with
      other nutrients in parenteral nutrition.Key words: hypocalcemia calcium gluconate
      calcium chloride aluminum parenteral nutrition.

PMID- 29351378
TI  - [Simplicia and medical containers from the Jesuit pharmacy in Telc].
AB  - The Jesuit pharmacy in Telc was founded after 1657 within the premises of the
      Jesuit cloister; it survived the dissolution of Jesuits in 1773 and thanks to its
      purchase by the last pharmacist Ignac Lyro it was relocated to one of the houses
      in the square. During the stocktaking of the property and its sale, a detailed
      inventory of pharmacy equipment was recorded, including cabinets, laboratory
      tools, ingredients or drugs. The inventory is divided into parts of ingredients
      and prepared medications, the last lists recording the tools and containers for
      its preparation, production and preservation. The ingredients contain various
      parts of plants, minerals, precious stones or even parts of animals. The list is
      written mainly in the alphabetical order, in some cases with specified types of
      groups. Every item is provided with information about its price and quantity.
      Many ingredients originated from overseas countries, the areas of Jesuit
      missionary activities. Of the former rich equipment, only three pharmacy cabinets
      and a few containers, mainly veneer boxes and ceramic drug jars, have survived.
      All these parts together with the inventory give us a comparatively clear notion
      about the equipment and even facilities of the Jesuit apothecary in Telc, which
      sold items from different parts of the world. The Jesuit convent seems to be an
      important centre for town inhabitants not only in the 18th century; its legacy
      has remained in the local pharmacy till today.Key words: pharmacy Societas Jesus
      18th century medications medical containers.

PMID- 29351379
TI  - [Synergistic effect of azole antimycotics (clotrimazole and fluconazole) and
      natural substances].
AB  - Nowadays the treatment of fungal infections is difficult due to increasing
      resistance of fungal pathogens to antimycotics. The efficacy of antimycotics can
      be increased by a proper combination of commercial drugs and natural substances.
      The 100% antimycotic activity was found using susceptibility testing of Candida
      albicans yeasts on clotrimazole alone and in combination with tea tree oil, or
      with a multicomponent preparation containing cannabis oil and various essential
      oils and in combination with propolis tincture. Combination of natural substances
      with fluconazole seems to be also prospective. Fluconazole alone achieved an
      antifungal activity of 80.95% but natural active substances increased its
      efficacy by 9.55-14.25%.Key words: Candida albicans fluconazole clotrimazole
      natural active substances synergism.

PMID- 29351380
TI  - The Clinical Impact of Different Adherence Behaviors in Patients with Severe
      Chronic Obstructive Pulmonary Disease.

PMID- 29351381
TI  - Frontal assessment battery (FAB) performance following traumatic brain injury
      hospitalized in an acute care setting.
AB  - The Frontal Assessment Battery (FAB) has been shown to be useful in several
      clinical settings. The aim of the present study was to examine the performance of
      patients with traumatic brain injury (TBI) on the FAB and to predict their acute
      outcome. The FAB was administered to 89 patients with mild (27 = uncomplicated
      and 39 = complicated) and moderate (n = 23) TBI during hospitalization in an
      acute care setting. The length of stay in days (LOS), Glasgow Outcome Scale
      Revised score (GOSE) and Disability Rating Scale (DRS) score were collected.
      Results showed no significant differences between the three groups on the FAB
      score, but age and education were significantly associated with the FAB score.
      Parietal lesions were associated with lower total FAB score, and with the
      Similarities, Motor series and Conflicting instructions subscales, while frontal
      lesions were associated with lower performance on the Motor series and
      Conflicting instructions subscales. Total FAB score was significantly correlated
      with all outcome measures, and together the FAB total score and the Glasgow Coma
      Scale (GCS) score explained 30.8% of the variance in the DRS score. The FAB may
      be useful clinically to acutely assess frontal and parietal lobe functions at
      bedside in patients with TBI and, in combination with the GCS score to measure
      TBI severity, can enable clinicians to predict early outcome.

PMID- 29351382
TI  - Team versus individual sport participation as a modifying factor in the
      development of post-concussion syndrome after first concussion: A pilot study.
AB  - Identification of modifying factors that influence the development of post
      concussion syndrome (PCS) following sport-related concussion (SRC) has drawn
      considerable interest. In this pilot study, we investigate the effect of team vs.
      individual sport participation on the development of PCS in a sample of 136 high
      school and college student-athletes. Controlling for several confounding
      variables, we employed a binary logistic regression and chi-squared test. Results
      of this pilot study indicate that participation in team versus individual sport
      is not a significant factor in the development of PCS. The identification of
      other forms of protective mechanisms is discussed.

PMID- 29351383
TI  - Muscular performance and body composition changes following multi-joint versus
      combined multi- and single-joint exercises in aging adults.
AB  - The aim of the present study was to compare muscular performance and body
      composition changes following low-volume resistance-training programs consisting
      of multi-joint (MJ) exercises (cable chest press and seated row) versus a
      combination of multi- and single-joint (MJ+SJ) exercises (cable chest press,
      seated row, biceps curl, and triceps extension). Thirty untrained healthy aging
      adults were randomly assigned to 3 groups: MJ (n = 11), MJ+SJ (n = 11), and
      control (n = 8). Twelve-repetition maximums (12-RMs) for the cable chest press
      and seated row, localized muscular endurance for the elbow flexors handgrip
      strength, and body composition were assessed before and after the 8-week training
      program. All comparisons were analyzed via a mixed-model analysis with repeated
      measures (group * time) and the Bonferroni post hoc test (p < 0.05). The MJ and
      MJ+SJ groups increased performance in the 12-RM cable chest press (MJ = 61.5% +/-
      24.6% and MJ+SJ = 71.1% +/- 25.6%), 12-RM seated row (MJ = 46.4% +/- 26.3% and
      MJ+SJ = 51.5% +/- 21.0%), localized muscular endurance (MJ = 24.7% +/- 16.7% and
      MJ+SJ = 37.0% +/- 11.4%), and handgrip strength (MJ = 9.3% +/- 10.4% and MJ+SJ =
      16.6% +/- 25.3%) after the intervention. Body composition (i.e., trunk and upper
      limb fat and lean mass) did not change for any groups. No significant differences
      were observed between the MJ versus the MJ+SJ protocols after the intervention
      for any variables. In conclusion, for aging adults, either MJ or MJ+SJ low-volume
      resistance training resulted in similar increases in 12-RM, localized muscular
      endurance, and handgrip strength, without changes in body composition after 8
      weeks of training.

PMID- 29351384
TI  - Association With Deviant Peers Across Adolescence: Subtypes, Developmental
      Patterns, and Long-Term Outcomes.
AB  - Indices of deviant peer group involvement are inconsistent and confound type,
      frequency, and severity of deviant peer behaviors. These measurement approaches
      thus obfuscate potential meaningful differences in deviant peer involvement in
      terms of subtypes, developmental patterns, and long-term outcomes. The current
      study employed latent class analysis to derive subtypes of deviant peer
      involvement and examined relations to substance use disorder in adulthood, a
      common outcome of deviant peer involvement. Youth (76% Caucasian) completed
      assessments across four time points: ages 10-12 years (Time 1; N = 775, 71%
      male), 12-14 years (Time 2; n = 649, 72% male), 16 years (Time 3; n = 613, 73%
      male), and 22 years (Time 4; n = 425, 71% male). At Times 1 to 3, participants
      completed an interview assessing deviant peer involvement. At Time 4,
      participants completed a structured interview assessing substance use disorder.
      Classes of youth with different profiles of deviant peer associations were
      derived at Times 1, 2, and 3. Classes varied by type (conduct problems vs.
      substance use) and severity of deviant peer behavior. Youth reported higher
      levels of involvement with deviant peers across adolescence, suggesting that some
      of these deviant peer behaviors may be normative. Earlier involvement with
      deviant peers and involvement with groups defined by severe conduct problems and
      substance use were related to the greatest risk for substance use disorder at
      Time 4. Type and severity of peer deviant behavior differentially relate to long
      term risk for substance use disorder and should be included in screening and
      assessment for risk across adolescence.

PMID- 29351385
TI  - Development of a recombinase polymerase amplification assay for Vibrio
      parahaemolyticus detection with an internal amplification control.
AB  - A novel RPA-IAC assay using recombinase polymerase and an internal amplification
      control (IAC) for Vibrio parahaemolyticus detection was developed. Specific
      primers were designed based on the coding sequence for the toxR gene in V.
      parahaemolyticus. The recombinase polymerase amplification (RPA) reaction was
      conducted at a constant low temperature of 37  degrees C for 20 min. Assay
      specificity was validated by using 63 Vibrio strains and 10 non-Vibrio bacterial
      species. In addition, a competitive IAC was employed to avoid false-negative
      results, which co-amplified simultaneously with the target sequence. The
      sensitivity of the assay was determined as 3 * 103 CFU/mL, which is decidedly
      more sensitive than the established PCR method. This method was then used to test
      seafood samples that were collected from local markets. Seven out of 53 different
      raw seafoods were detected as V. parahaemolyticus-positive, which were consistent
      with those obtained using traditional culturing method and biochemical assay.
      This novel RPA-IAC assay provides a rapid, specific, sensitive, and more
      convenient detection method for V. parahaemolyticus.

PMID- 29351387
TI  - Letter to the editor: Low-carb meal plan and postmeal exercise.

PMID- 29351388
TI  - Retraction.

PMID- 29351386
TI  - Protective effect of C-peptide on experimentally induced diabetic nephropathy and
      the possible link between C-peptide and nitric oxide.
AB  - Diabetic nephropathy one of the major microvascular diabetic complications.
      Besides hyperglycemia, other factors contribute to the development of diabetic
      complications as the proinsulin connecting peptide, C-peptide. We described the
      role of C-peptide replacement therapy on experimentally induced diabetic
      nephropathy, and its potential mechanisms of action by studying the role of
      nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its
      production by NG-nitro-l-arginine methyl ester (L-NAME). Renal injury markers
      measured were serum urea, creatinine, tumor necrosis factor alpha, and
      angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal
      tissue. In conclusion, diabetic induction resulted in islet degenerations and
      decreased insulin secretion with its metabolic consequences and subsequent renal
      complications. C-Peptide deficiencies in diabetes might have contributed to the
      metabolic and renal error, since C-peptide treatment to the diabetic rats
      completely corrected these errors. The beneficial effects of C-peptide are
      partially antagonized by L-NAME coadministration, indicating that NO partially
      mediates C-peptide effects.

PMID- 29351389
TI  - Proliferation of hepatic stellate cells, mediated by YAP and TAZ, contributes to
      liver repair and regeneration after liver ischemia-reperfusion injury.
AB  - Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding
      motif (TAZ) are key regulators of cell proliferation and organ size; however,
      their physiological contribution after liver injury has not been fully
      understood. In this study, we sought to determine the role of YAP and TAZ during
      liver recovery after ischemia-reperfusion (I/R). A murine model of partial (70%)
      I/R was used to induce liver injury and study the reparative and regenerative
      response. After liver injury, there was marked activation and proliferation of
      hepatic stellate cells. The Hippo pathway components, large tumor suppressor 1
      (LATS1) and its adapter protein, Mps one binder 1 (MOB1), were inactivated during
      liver repair, and YAP and TAZ were activated selectively in hepatic stellate
      cells. Concurrently, the expression of connective tissue growth factor and
      survivin, both of which are YAP and TAZ target genes, were upregulated. Hepatic
      stellate cell expansion and concomitant activation of YAP and TAZ occurred only
      in the injured liver and were not observed in the nonischemic liver. Treatment of
      mice with verteporfin, an inhibitor of YAP and TAZ, decreased hepatic stellate
      cell proliferation, survivin, and cardiac ankyrin repeat protein expression.
      These changes were associated with a significant decrease in hepatocyte
      proliferation. The data suggest that liver repair and regeneration after I/R
      injury are dependent on hepatic stellate cell proliferation, which is mediated by
      YAP and TAZ. NEW & NOTEWORTHY This study is the first to assess the proliferation
      of hepatic stellate cells (HSCs) after ischemia-reperfusion (I/R) injury and
      their role in the reparative and regenerative process. Here we show that the
      Hippo pathway is inactivated after I/R and that Yes-associated
      protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) activation
      is detected in HSC. HSC proliferation and expansion are prominent during liver
      recovery after I/R injury. Inhibition of YAP/TAZ activation with verteporfin
      reduces HSC proliferation and target gene expression and attenuates hepatocyte
      proliferation.

PMID- 29351391
TI  - The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic
      epithelial wound healing.
AB  - The intestinal epithelium constitutes an innate barrier which, upon injury,
      undergoes self-repair processes known as restitution. Although bile acids are
      known as important regulators of epithelial function in health and disease, their
      effects on wound healing processes are not yet clear. Here we set out to
      investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and
      ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T84 cell
      monolayers grown on transparent, permeable supports was assessed over 48 h with
      or without bile acids. Cell migration was measured in Boyden chambers. mRNA and
      protein expression were measured by RT-PCR and Western blotting. DCA (50-150 uM)
      significantly inhibited wound closure in cultured epithelial monolayers and
      attenuated cell migration in Boyden chamber assays. DCA also induced nuclear
      accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064
      (10 uM), inhibited wound closure. Both DCA and GW4064 attenuated the expression
      of CFTR Cl- channels, whereas inhibition of CFTR activity with either CFTR-inh
      172 (10 uM) or GlyH-101 (25 uM) also prevented wound healing. Promoter/reporter
      assays revealed that FXR-induced downregulation of CFTR is mediated at the
      transcriptional level. In contrast, UDCA (50-150 uM) enhanced wound healing in
      vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted
      mucosal healing in an in vivo mouse model. In conclusion, these studies suggest
      bile acids are important regulators of epithelial wound healing and are therefore
      good targets for development of new drugs to modulate intestinal barrier function
      in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid,
      inhibits colonic epithelial wound healing, an effect which appears to be mediated
      by activation of the nuclear bile acid receptor, FXR, with subsequent
      downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid
      promotes wound healing, suggesting it may provide an alternative approach to
      prevent the losses of barrier function that are associated with mucosal
      inflammation in IBD patients.

PMID- 29351390
TI  - Vagally mediated gastric effects of brain stem alpha2-adrenoceptor activation in
      stressed rats.
AB  - Chronic stress exerts vagally dependent effects to disrupt gastric motility;
      previous studies have shown that, among other nuclei, A2 neurons are involved in
      mediating these effects. Several studies have also shown robust in vitro and in
      vivo effects of alpha2-adrenoceptor agonists on vagal motoneurons. We have
      demonstrated previously that brainstem vagal neurocircuits undergo remodeling
      following acute stress; however, the effects following brief periods of chronic
      stress have not been investigated. Our aim, therefore, was to test the hypothesis
      that different types of chronic stress influence gastric tone and motility by
      inducing plasticity in the response of vagal neurocircuits to alpha2
      adrenoreceptor agonists. In rats that underwent 5 days of either homotypic or
      heterotypic stress loading, we applied the alpha2-adrenoceptor agonist, UK14304,
      either by in vitro brainstem perfusion to examine its ability to modulate
      GABAergic synaptic inputs to vagal motoneurons or in vivo brainstem
      microinjection to observe actions to modulate antral tone and motility. In
      neurons from naive rats, GABAergic currents were unresponsive to exogenous
      application of UK14304. In contrast, GABAergic currents were inhibited by UK14304
      in all neurons from homotypic and, in a subpopulation of neurons, heterotypic
      stressed rats. In control rats, UK14304 microinjection inhibited gastric tone and
      motility via withdrawal of vagal cholinergic tone; in heterotypic stressed rats,
      the larger inhibition of antrum tone was due to a concomitant activation of
      peripheral nonadrenergic, noncholinergic pathways. These data suggest that stress
      induces plasticity in brainstem vagal neurocircuits, leading to an upregulation
      of alpha2-mediated responses. NEW & NOTEWORTHY Catecholaminergic neurons of the
      A2 area play a relevant role in stress-related dysfunction of the gastric antrum.
      Brief periods of chronic stress load induce plastic changes in the actions of
      adrenoceptors on vagal brainstem neurocircuits.

PMID- 29351392
TI  - Young mice expel the tapeworm Hymenolepis diminuta and are protected from colitis
      by triggering a memory response with worm antigen.
AB  - Infection with helminth parasites reduces the severity of concomitant
      inflammatory disease in adult mice. There is an alarming increase of inflammatory
      bowel disease (IBD) in children. It is important to determine whether helminth
      therapy would be of value in pediatric IBD and whether triggering immunological
      memory to the worm would be anticolitic. Three-week-old (young) and eight-week
      old (adult) Balb/c mice were infected with H. diminuta, and infectivity and T
      helper 2 (Th2) immunity were assessed. Other mice received H. diminuta with or
      without a crude worm extract ( HdE) 28-42 days postinfection (dpi) with or
      without dinitrobenzene sulphonic acid [DNBS, 1.5 mg (young) or 3 mg (adults),
      ir], and colitis was assessed 72 h later. Infected young mice developed Th2
      immunity and expelled H. diminuta; expulsion was delayed by ~2 days compared with
      adult mice. Colitis, as gauged by macroscopic disease and histopathology scores,
      was less severe in young mice infected 10 days, but not 8 days, before DNBS.
      Protection against DNBS-induced colitis was accompanied by an increased capacity
      to make interleukin (IL)-4 and IL-10. Mice infected with H. diminuta were not
      protected from DNBS-colitis when challenged 28 days later; however, injection of
      these mice with HdE coincident with DNBS resulted in less disease and increased
      splenic IL-4 and IL-10. Using a boost (500 MUg HdE, 28 dpi) and repeat HdE (100
      MUg, 42 dpi) regimen with infected mice suppressed DNBS-colitis, as did adoptive
      transfer of splenic CD4+ T cells from infected mice with low-dose HdE challenge.
      Should these data translate to IBD, then helminth therapy could be of value in
      pediatric-onset IBD, and defining the antigen(s) that elicit antihelminth
      immunological memory could serve as an anticolitic approach in previously
      infected individuals. NEW & NOTEWORTHY This study demonstrates that juvenile mice
      are protected from colitis by infection with the tapeworm Hymenolepis diminuta
      and that using worm antigen to trigger an immunological memory response in
      previously infected mice can be used to limit the severity of colitis.

PMID- 29351394
TI  - Bile acid profiles within the enterohepatic circulation in a diabetic rat model
      after bariatric surgeries.
AB  - Bile acids (BAs), which are synthesized in the liver and cycled in the
      enterohepatic circulation, have been recognized as signaling molecules by
      activating their receptors in the intestine and liver. Serum taurine-conjugated
      BAs have been shown to be elevated after bariatric surgeries although the
      postoperative BA profiles within the enterohepatic circulation have not been
      investigated. Clarification of these profiles could help explain the mechanisms
      by which bariatric surgery leads to BA profile alterations and subsequent
      metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy
      (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet
      and streptozotocin. The weight loss and antidiabetic effects were evaluated
      postsurgery. BA profiles in the systemic serum and within the enterohepatic
      circulation were analyzed, together with the expression of related BA
      transporters and enzymes at week 12 after surgery. Compared with sham, SG induced
      sustained weight loss, and both DJB and SG significantly improved glucose
      tolerance and insulin sensitivity with enhanced glucagon-like peptide 1
      secretion. Similar to changes in the serum, BAs, especially taurine-conjugated
      species, were also elevated in the enterohepatic circulation (bile and portal
      vein) after DJB and SG. In addition, the expression of key BA transporters and
      conjugational enzymes was elevated postoperatively, whereas the enzymes
      responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated
      BA levels in the systemic serum and enterohepatic circulation, especially taurine
      conjugated species, which likely indicates increased ileal reabsorption and
      hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have
      been implicated as potential mediators of the weight-independent effects of
      bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass
      and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species
      in the enterohepatic circulation, likely through the promotion of ileal
      reabsorption and hepatic conjugation rather than BA synthesis. These findings
      will improve our understanding of BA metabolism after bariatric surgery and their
      subsequent metabolic effects.

PMID- 29351393
TI  - Liver tissue metabolically transformed by alcohol induces immune recognition of
      liver self-proteins but not in vivo inflammation.
AB  - Precision-cut liver slices (PCLSs) provide a novel model for studies of alcoholic
      liver disease (ALD). This is relevant, as in vivo ethanol exposure does not
      appear to generate significant liver damage in ethanol-fed mice, except in the
      National Institute on Alcohol Abuse and Alcoholism binge model of ALD. Previous
      studies have shown that the two metabolites of ethanol consumption,
      malondialdhyde (MDA) and acetaldehyde (AA), combine to form MDA-AA (MAA) adducts,
      which have been correlated with the development and progression of ALD. In this
      study, murine PCLSs were incubated with ethanol and examined for the production
      of MAA adducts. PCLSs were homogenized, and homogenates were injected into
      C57BL/6 mice. PCLSs from control-, pair-, and ethanol-fed animals served as
      targets in in situ cytotoxic assays using primed T cells from mice hyperimmunized
      with control or ethanol-exposed PCLS homogenates. A CD45.1/CD45.2 passive
      transfer model was used to determine whether T cells from the spleens of mice
      hyperimmunized with PCLS ethanol-exposed homogenates trafficked to the liver.
      PCLSs incubated with ethanol generated MAA-modified proteins in situ. Cytotoxic
      (CD8+) T cells from immunized mice killed naive PCLSs from control- and pair-fed
      mice in vitro, a response that was blunted in PCLSs from ethanol-fed mice.
      Furthermore, CD45.1 CD8+ T cells from hyperimmunized mice trafficked to the liver
      but did not initiate liver damage. This study demonstrates that exposure to liver
      tissue damaged by ethanol mediates robust immune responses to well-characterized
      alcohol metabolites and native liver proteins in vitro. Moreover, although these
      proinflammatory T cells traffic to the liver, these responses appear to be
      dampened in vivo by locally acting pathways. NEW & NOTEWORTHY This study shows
      that the metabolites of ethanol and lipid breakdown produce malondialdehyde
      acetaldehyde adducts in the precision-cut liver slice model system. Additionally,
      precision-cut liver slices exposed to ethanol and harboring malondialdehyde
      acetaldehyde adducts generate liver-specific antibody and T cell responses in the
      spleens of naive mice that could traffic to the liver.

PMID- 29351396
TI  - Mechanisms of repetitive retrograde contractions in response to sustained
      esophageal distension: a study evaluating patients with postfundoplication
      dysphagia.
AB  - Repetitive retrograde contractions (RRCs) in response to sustained esophageal
      distension are a distinct contractility pattern observed with functional luminal
      imaging probe (FLIP) panometry that are common in type III (spastic) achalasia.
      RRCs are hypothesized to be indicative of either impaired inhibitory innervation
      or esophageal outflow obstruction. We aimed to apply FLIP panometry to patients
      with postfundoplication dysphagia (a model of esophageal obstruction) to explore
      mechanisms behind RRCs. Adult patients with dysphagia after Nissen fundoplication
      ( n = 32) or type III achalasia ( n = 25) were evaluated with high-resolution
      manometry (HRM) and upper endoscopy with FLIP. HRM studies were assessed for
      outflow obstruction and spastic features: premature contractility,
      hypercontractility, and impaired deglutitive inhibition during multiple-rapid
      swallows. FLIP studies were analyzed to determine the esophagogastric junction
      (EGJ)-distensibility index and contractility pattern, including RRCs. Barium
      esophagram was evaluated when available. RRCs were present in 8/32 (25%)
      fundoplication and 19/25 (76%) achalasia patients ( P < 0.001). EGJ outflow
      obstruction was detected in 21 (67%) fundoplication patients by HRM, FLIP, or
      esophagram [6 (29%) had RRCs]. On HRM, none of the fundoplication patients had
      premature contractility, whereas 3/4 with defective inhibition on multiple-rapid
      swallows and 2/4 with hypercontractility had RRCs. Regression analysis
      demonstrated HRM with spastic features, but not esophageal outflow obstruction,
      as a predictor for RRCs. RRCs in response to sustained esophageal distension
      appear to be a manifestation of spastic esophageal motility. Although future
      study to further clarify the significance of RRCs is needed, RRCs on FLIP
      panometry should prompt evaluation for a major motor disorder. NEW & NOTEWORTHY
      Repetitive retrograde contractions (RRCs) are a common response to sustained
      esophageal distension among spastic achalasia patients when evaluated with the
      functional luminal imaging probe. We evaluated patients with postfundoplication
      dysphagia, i.e., patients with suspected mechanical obstruction, and found that
      RRCs occasionally occurred among postfundoplication patients, but often in
      association with manometric features of esophageal neuromuscular imbalance. Thus,
      RRCs appear to be a manifestation of spastic esophageal dysmotility, likely from
      neural imbalance resulting in excess excitation.

PMID- 29351397
TI  - Acute small intestinal inflammation results in persistent lymphatic alterations.
AB  - Inflammatory bowel disease (IBD) has a complex pathophysiology with limited
      treatments. Structural and functional changes in the intestinal lymphatic system
      have been associated with the disease, with increased risk of IBD occurrence
      linked to a history of acute intestinal injury. To examine the potential role of
      the lymphatic system in inflammation recurrence, we evaluated morphological and
      functional changes in mouse mucosal and mesenteric lymphatic vessels, and within
      the mesenteric lymph nodes during acute ileitis caused by a 7-day treatment with
      dextran sodium sulfate (DSS). We monitored whether the changes persisted during a
      14-day recovery period and determined their potential consequences on dendritic
      cell (DC) trafficking between the mucosa and lymphoid tissues. DSS administration
      was associated with marked lymphatic abnormalities and dysfunctions exemplified
      by lymphangiectasia and lymphangiogenesis in the ileal mucosa and mesentery,
      increased mesenteric lymphatic vessel leakage, and lymphadenopathy.
      Lymphangiogenesis and lymphadenopathy were still evident after recovery from
      intestinal inflammation and correlated with higher numbers of DCs in mucosal and
      lymphatic tissues. Specifically, a deficit in CD103+ DCs observed during acute
      DSS in the lamina propria was reversed and further enhanced during recovery. We
      concluded that an acute intestinal insult caused alterations of the mesenteric
      lymphatic system, including lymphangiogenesis, which persisted after resolution
      of inflammation. These morphological and functional changes could compromise DC
      function and movement, increasing susceptibility to further gastrointestinal
      disease. Elucidation of the changes in mesenteric and intestinal lymphatic
      function should offer key insights for new therapeutic strategies in
      gastrointestinal disorders such as IBD. NEW & NOTEWORTHY Lymphatic integrity
      plays a critical role in small intestinal homeostasis. Acute intestinal insult in
      a mouse model of acute ileitis causes morphological and functional changes in
      mesenteric and intestinal lymphatic vessels. While some of the changes
      significantly regressed during inflammation resolution, others persisted,
      including lymphangiogenesis and altered dendritic cell function and movement,
      potentially increasing susceptibility to the recurrence of gastrointestinal
      inflammation.

PMID- 29351395
TI  - Macrophage colony-stimulating factor increases hepatic macrophage content, liver
      growth, and lipid accumulation in neonatal rats.
AB  - Signaling via the colony-stimulating factor 1 receptor (CSF1R) controls the
      survival, differentiation, and proliferation of macrophages. Mutations in CSF1 or
      CSF1R in mice and rats have pleiotropic effects on postnatal somatic growth. We
      tested the possible application of pig CSF1-Fc fusion protein as a therapy for
      low birth weight (LBW) at term, using a model based on maternal dexamethasone
      treatment in rats. Neonatal CSF1-Fc treatment did not alter somatic growth and
      did not increase the blood monocyte count. Instead, there was a substantial
      increase in the size of liver in both control and LBW rats, and the treatment
      greatly exacerbated lipid droplet accumulation seen in the dexamethasone LBW
      model. These effects were reversed upon cessation of treatment. Transcriptional
      profiling of the livers supported histochemical evidence of a large increase in
      macrophages with a resident Kupffer cell phenotype and revealed increased
      expression of many genes implicated in lipid droplet formation. There was no
      further increase in hepatocyte proliferation over the already high rates in
      neonatal liver. In conclusion, treatment of neonatal rats with CSF1-Fc caused an
      increase in liver size and hepatic lipid accumulation, due to Kupffer cell
      expansion and/or activation rather than hepatocyte proliferation. Increased liver
      macrophage numbers and expression of endocytic receptors could mitigate defective
      clearance functions in neonates. NEW & NOTEWORTHY This study is based on
      extensive studies in mice and pigs of the role of CSF1/CSF1R in macrophage
      development and postnatal growth. We extended the study to neonatal rats as a
      possible therapy for low birth weight. Unlike our previous studies in mice and
      pigs, there was no increase in hepatocyte proliferation and no increase in
      monocyte numbers. Instead, neonatal rats treated with CSF1 displayed reversible
      hepatic steatosis and Kupffer cell expansion.

PMID- 29351398
TI  - Visceral hypersensitivity induced by optogenetic activation of the amygdala in
      conscious rats.
AB  - In vivo optogenetics identifies brain circuits controlling behaviors in conscious
      animals by using light to alter neuronal function and offers a novel tool to
      study the brain-gut axis. Using adenoviral-mediated expression, we aimed to
      investigate whether photoactivation with channelrhodopsin (ChR2) or
      photoinhibition with halorhodopsin (HR3.0) of fibers originating from the central
      nucleus of the amygdala (CeA) at the bed nucleus of the stria terminalis (BNST)
      had any effect on colonic sensitivity. We also investigated whether there was any
      deleterious effect of the adenovirus on the neuronal population or the neuronal
      phenotype within the CeA-BNST circuitry activated during the optogenetic
      stimulation. In male rats, the CeA was infected with vectors expressing ChR2 or
      HR3.0 and fiber optic cannulae were implanted on the BNST. After 8-10 wk, the
      response to graded, isobaric colonic distension was measured with and without
      laser stimulation of CeA fibers at the BNST. Immunohistochemistry and histology
      were used to evaluate vector expression, neuronal integrity, and neurochemical
      phenotype. Photoactivation of CeA fibers at the BNST with ChR2 induced colonic
      hypersensitivity, whereas photoinhibition of CeA fibers at the BNST with HR3.0
      had no effect on colonic sensitivity. Control groups treated with virus
      expressing reporter proteins showed no abnormalities in neuronal morphology,
      neuronal number, or neurochemical phenotype following laser stimulation. Our
      experimental findings reveal that optogenetic activation of discrete brain nuclei
      can be used to advance our understanding of complex visceral nociceptive
      circuitry in a freely moving rat model. NEW & NOTEWORTHY Our findings reveal that
      optogenetic technology can be employed as a tool to advance understanding of the
      brain-gut axis. Using adenoviral-mediated expression of opsins, which were
      activated by laser light and targeted by fiber optic cannulae, we examined
      central nociceptive circuits mediating visceral pain in a freely moving rat.
      Photoactivation of amygdala fibers in the stria terminalis with channelrhodopsin
      induced colonic hypersensitivity, whereas inhibition of the same fibers with
      halorhodopsin did not alter colonic sensitivity.

PMID- 29351400
TI  - Corrigendum.

PMID- 29351399
TI  - Corrigendum.

PMID- 29351401
TI  - Corrigendum.

PMID- 29351402
TI  - Poststroke delusions: What about the neuroanatomical and neurofunctional basis?
AB  - Delusion is a belief about yourself, people, or events that has no accordance
      with reality. Although it is known that stroke could cause various psychiatric
      and psychological effects, including depression, anxiety, and aggressiveness,
      psychotic symptoms, especially delusions, are rather uncommon. The most
      investigated poststroke delusions are paranoid type, nihilistic, and Fregoli
      syndrome. We will describe two patients showing delusion symptoms (Cotard-like
      and erotomanic ones) that occurred after a stroke involving the right temporal
      lobe, the basal ganglia and insular region, persisting for a long period after
      the stroke onset. We have, therefore, supposed that the simultaneous involvement
      of these brain areas could be involved in the neuroanatomical basis of delusions,
      as also demonstrated by the neurofunctional evaluation.

PMID- 29351403
TI  - Project on the Good Physician: Further Evidence for the Validity of a Moral
      Intuitionist Model of Virtuous Caring.
AB  - THEORY: In the Project on the Good Physician, the authors propose a moral
      intuitionist model of virtuous caring that places the virtues of Mindfulness,
      Empathic Compassion, and Generosity at the heart of medical character education.
      HYPOTHESES: Hypothesis 1a: The virtues of Mindfulness, Empathic Compassion, and
      Generosity will be positively associated with one another (convergent validity).
      Hypothesis 1b: The virtues of Mindfulness and Empathic Compassion will explain
      variance in the action-related virtue of Generosity beyond that predicted by Big
      Five personality traits alone (discriminant validity). Hypothesis 1c: Virtuous
      students will experience greater well-being ("flourishing"), as measured by four
      indices of well-being: life meaning, life satisfaction, vocational identity, and
      vocational calling (predictive validity). Hypothesis 1d: Students who self-report
      higher levels of the virtues will be nominated by their peers for the Gold
      Humanism Award (predictive validity). Hypothesis 2a-2c: Neuroticism and Burnout
      will be positively associated with each other and inversely associated with
      measures of virtue and well-being. METHOD: The authors used data from a 2011
      nationally representative sample of U.S. medical students (n = 499) in which
      medical virtues (Mindfulness, Empathic Compassion, and Generosity) were measured
      using scales adapted from existing instruments with validity evidence. RESULTS:
      Supporting the predictive validity of the model, virtuous students were
      recognized by their peers to be exemplary doctors, and they were more likely to
      have higher ratings on measures of student well-being. Supporting the
      discriminant validity of the model, virtues predicted prosocial behavior
      (Generosity) more than personality traits alone, and students higher in the
      virtue of Mindfulness were less likely to be high in Neuroticism and Burnout.
      CONCLUSIONS: Data from this descriptive-correlational study offered additional
      support for the validity of the moral intuitionist model of virtuous caring.
      Applied to medical character education, medical school programs should consider
      designing educational experiences that intentionally emphasize the cultivation of
      virtue.

PMID- 29351404
TI  - Type 2 diabetes impairs the ability of skeletal muscle pericytes to augment
      postischemic neovascularization in db/db mice.
AB  - Peripheral artery disease is an atherosclerotic occlusive disease that causes
      limb ischemia and has few effective noninterventional treatments. Stem cell
      therapy is promising, but concomitant diabetes may limit its effectiveness. We
      evaluated the therapeutic potential of skeletal muscle pericytes to augment
      postischemic neovascularization in wild-type and type 2 diabetic (T2DM) mice.
      Wild-type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice
      underwent unilateral femoral artery excision to induce limb ischemia. Twenty-four
      hours after ischemia induction, CD45-CD34-CD146+ skeletal muscle pericytes or
      vehicle controls were transplanted into ischemic hindlimb muscles. At
      postoperative day 28, pericyte transplantation augmented blood flow recovery in
      wild-type mice (79.3 +/- 5% vs. 61.9 +/- 5%; P = 0.04), but not in T2DM mice
      (48.6% vs. 46.3 +/- 5%; P = 0.51). Pericyte transplantation augmented collateral
      artery enlargement in wild-type (26.7 +/- 2 MUm vs. 22.3 +/- 1 MUm, P = 0.03),
      but not T2DM mice (20.4 +/- 1.4 MUm vs. 18.5 +/- 1.2 MUm, P = 0.14). Pericyte
      incorporation into collateral arteries was higher in wild-type than in T2DM mice
      ( P = 0.002). Unexpectedly, pericytes differentiated into Schwann cells in vivo.
      In vitro, Insulin increased Nox2 expression and decreased tubular formation
      capacity in human pericytes. These insulin-induced effects were reversed by N
      acetylcysteine antioxidant treatment. In conclusion, T2DM impairs the ability of
      pericytes to augment neovascularization via decreased collateral artery
      enlargement and impaired engraftment into collateral arteries, potentially via
      hyperinsulinemia-induced oxidant stress. While pericytes show promise as a unique
      form of stem cell therapy to increase postischemic neovascularization,
      characterizing the molecular mechanisms by which T2DM impairs their function is
      essential to achieve their therapeutic potential.

PMID- 29351405
TI  - Acute downregulation of miR-199a attenuates sepsis-induced acute lung injury by
      targeting SIRT1.
AB  - MicroRNA-199a (miR-199a) is a novel gene regulator with an important role in
      inflammation and lung injury. However, its role in the pathogenesis of sepsis
      induced acute respiratory distress syndrome (ARDS) is currently unknown. Our
      study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of
      action. First, we found that LPS could upregulate miR-199a in alveolar
      macrophages. Downregulation of miR-199a inhibited the upregulation of
      inflammatory cytokines in alveolar macrophages and induced the remission of
      histopathologic changes, the reduction of proinflammatory cytokines, and the
      upregulation of apoptosis protein expression in an ARDS lung, showing a
      protective role for miR-199a. We further identified sirtuin 1 (SIRT1) as a direct
      target of miR-199a in alveolar macrophages, and the expression of SIRT1 was
      negatively correlated with the level of miR-199a. The protective role of miR-199a
      downregulation in LPS-stimulated alveolar macrophages and sepsis-induced ARDS
      could be attenuated by SIRT1 inhibitor. Taken together, these results indicate
      that downregulation of miR-199a might protect lung tissue against sepsis-induced
      ARDS by upregulation of SIRT1 through the suppression of excessive inflammatory
      responses and the inhibition of cellular apoptosis in lung tissue, suggesting its
      potential therapeutic effects on sepsis-induced ARDS.

PMID- 29351406
TI  - Interleukin-6 promotes a sustained loss of endothelial barrier function via Janus
      kinase-mediated STAT3 phosphorylation and de novo protein synthesis.
AB  - Vascular leakage is a hallmark of the inflammatory response. Acute changes in
      endothelial permeability are due to posttranslational changes in intercellular
      adhesion and cytoskeleton proteins. However, little is known about the mechanisms
      leading to long-term changes in vascular permeability. Here, we show that
      interleukin-6 (IL-6) promotes an increase in endothelial monolayer permeability
      that lasts over 24 h and demonstrate that activation of Src and MEK/ERK pathways
      is required only for short-term increases in permeability, being dispensable
      after 2 h. In contrast, Janus kinase (JAK)-mediated STAT3 phosphorylation at Y705
      (but not S727) and de novo synthesis of RNA and proteins are required for the
      sustained permeability increases. Loss of junctional localization of VE-cadherin
      and ZO-1 is evident several hours after the maximal IL-6 response, thus
      suggesting that these events are a consequence of IL-6 signaling, but not a cause
      of the increased permeability. Understanding the mechanisms involved in
      sustaining vascular permeability may prove crucial to allow us to directly target
      vascular leakage and minimize tissue damage, thus reducing the rates of mortality
      and chronic sequelae of excessive edema. Targeting endothelial-specific
      mechanisms regulating barrier function could provide a new therapeutic strategy
      to prevent vascular leakage while maintaining the immune response and other
      beneficial aspects of the inflammatory response that are required for bacterial
      clearance and tissue repair.

PMID- 29351407
TI  - PEDF expression affects the oxidative and inflammatory state of choroidal
      endothelial cells.
AB  - Age-related macular degeneration (AMD) is the leading cause of vision loss among
      the elderly population, and is associated with severe macular degeneration and
      choroidal neovascularization (CNV). Although the pathogenesis of AMD is
      associated with choroidal dysfunction and CNV, the detailed underlying mechanisms
      remain unresolved. Altered production of pigment epithelium-derived factor
      (PEDF), a neuroprotective and antiangiogenic factor, contributes to CNV.
      Furthermore, exogenous PEDF mitigates angiogenesis in preclinical CNV models. How
      PEDF expression affects choroidal endothelial cell (ChEC) function is unknown.
      Here we isolated ChECs from PEDF+/+ and PEDF-deficient (PEDF-/-) mice and
      determined the impact of PEDF expression on the proangiogenic and pro
      inflammatory properties of ChECs. We showed that PEDF expression significantly
      affects the proliferation, migration, adhesion, and oxidative and inflammatory
      state of ChECs. The PEDF-/- ChECs were, however, more sensitive to H2O2 challenge
      and exhibited increased rate of apoptosis and oxidative stress. We also observed
      a significant increase in production of cytokines with a primary role in
      inflammation and angiogenesis including vascular endothelial growth factor (VEGF)
      and osteopontin, and a reprograming of chemokines and cytokines expression
      profiles in PEDF-/- ChECs. Collectively, our results indicate that PEDF
      expression has a significant impact on oxidative and inflammatory properties of
      ChECs, whose alteration could contribute to pathogenesis of chronic inflammatory
      diseases including exudative AMD.

PMID- 29351408
TI  - Choroid plexus epithelial cells express the adhesion protein P-cadherin at cell
      cell contacts and syntaxin-4 in the luminal membrane domain.
AB  - The choroid plexus epithelial cells (CPECs) belong to a small group of polarized
      cells, where the Na+-K+-ATPase is expressed in the luminal membrane. The basic
      polarity of the cells is, therefore, still debated. We investigated the
      subcellular distribution of an array of proteins known to play fundamental roles
      either in establishing and maintaining basic cell polarity or in the polarized
      delivery and recycling of plasma membrane proteins. Immunofluorescence
      histochemical analysis was applied to determine the subcellular localization of
      apical and basolateral membrane determinants. Mass spectrometry analysis of CPECs
      isolated by fluorescence-activated cell sorting was applied to determine the
      expression of specific forms of the proteins. CPECs mainly express the cell
      adhesive P-cadherin, which is localized to the lateral membranes. Proteins
      belonging to the Crumbs and partitioning defective (Par) protein complexes were
      all localized to the luminal membrane domain. Par-1 and the Scribble complex were
      localized to the basolateral membrane domain. Lethal(2) giant larvae homolog 2
      (Lgl2) labeling was preferentially observed in the luminal membrane domain.
      Phosphatidylinositol 3,4,5-trisphosphate (PIP3) was immunolocalized to the
      basolateral membrane domain, while phosphatidylinositol 4,5-bisphosphate (PIP2)
      staining was most prominent in the luminal membrane domain along with the PIP3
      phosphatase, Pten. The apical target-SNARE syntaxin-3 and the basolateral target
      SNARE syntaxin-4 were both localized to the apical membrane domain in CPECs,
      which lack cellular expression of the clathrin adaptor protein AP-1B for
      basolateral protein recycling. In conclusion, the CPECs are conventionally
      polarized, but express P-cadherin at cell-cell contacts, and Lgl2 and syntaxin-4
      in the luminal plasma membrane domain.

PMID- 29351409
TI  - Pharmacological activation of PPARgamma inhibits hypoxia-induced proliferation
      through a caveolin-1-targeted and -dependent mechanism in PASMCs.
AB  - Previously, we and others have demonstrated that activation of peroxisome
      proliferator-activated receptor gamma (PPARgamma) by specific pharmacological
      agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary
      hypertension (CHPH) by suppressing the proliferation and migration in distal
      pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial
      effects of PPARgamma are mediated by targeting the intracellular calcium
      homeostasis and store-operated calcium channel (SOCC) proteins, including the
      main caveolae component caveolin-1. However, other than the caveolin-1 targeted
      mechanism, in this study, we further uncovered a caveolin-1 dependent mechanism
      within the activation of PPARgamma by the specific agonist GW1929. First,
      effective knockdown of caveolin-1 by small-interfering RNA (siRNA) markedly
      abolished the upregulation of GW1929 on PPARgamma expression at both mRNA and
      protein levels; Then, in HEK293T, which has previously been reported with low
      endogenous caveolin-1 expression, exogenous expression of caveolin-1
      significantly enhanced the upregulation of GW1929 on PPARgamma expression
      compared with nontransfection control. In addition, inhibition of PPARgamma by
      either siRNA or pharmacological inhibitor T0070907 led to increased
      phosphorylation of cellular mitogen-activated protein kinases ERK1/2 and p38. In
      parallel, GW1929 dramatically decreased the expression of the proliferative
      regulators (cyclin D1 and PCNA), whereas it increased the apoptotic factors (p21,
      p53, and mdm2) in hypoxic PASMCs. Furthermore, these effects of GW1929 could be
      partially reversed by recovery of the drug treatment. In combination, PPARgamma
      activation by GW1929 reversibly drove the cell toward an antiproliferative and
      proapoptotic phenotype in a caveolin-1-dependent and -targeted mechanism.

PMID- 29351410
TI  - Hypoxia selectively upregulates cation channels and increases cytosolic [Ca2+] in
      pulmonary, but not coronary, arterial smooth muscle cells.
AB  - Ca2+ signaling, particularly the mechanism via store-operated Ca2+ entry (SOCE)
      and receptor-operated Ca2+ entry (ROCE), plays a critical role in the development
      of acute hypoxia-induced pulmonary vasoconstriction and chronic hypoxia-induced
      pulmonary hypertension. This study aimed to test the hypothesis that chronic
      hypoxia differentially regulates the expression of proteins that mediate SOCE and
      ROCE [stromal interacting molecule (STIM), Orai, and canonical transient receptor
      potential channel TRPC6] in pulmonary (PASMC) and coronary (CASMC) artery smooth
      muscle cells. The resting cytosolic [Ca2+] ([Ca2+]cyt) and the stored [Ca2+] in
      the sarcoplasmic reticulum were not different in CASMC and PASMC. Seahorse
      measurement showed a similar level of mitochondrial bioenergetics (basal
      respiration and ATP production) between CASMC and PASMC. Glycolysis was
      significantly higher in PASMC than in CASMC. The amplitudes of cyclopiazonic acid
      induced SOCE and OAG-induced ROCE in CASMC are slightly, but significantly,
      greater than in PASMC. The frequency and the area under the curve of Ca2+
      oscillations induced by ATP and histamine were also larger in CASMC than in
      PASMC. Na+/Ca2+ exchanger-mediated increases in [Ca2+]cyt did not differ
      significantly between CASMC and PASMC. The basal protein expression levels of
      STIM1/2, Orai1/2, and TRPC6 were higher in CASMC than in PASMC, but hypoxia (3%
      O2 for 72 h) significantly upregulated protein expression levels of STIM1/STIM2,
      Orai1/Orai2, and TRPC6 and increased the resting [Ca2+]cyt only in PASMC, but not
      in CASMC. The different response of essential components of store-operated and
      receptor-operated Ca2+ channels to hypoxia is a unique intrinsic property of
      PASMC, which is likely one of the important explanations why hypoxia causes
      pulmonary vasoconstriction and induces pulmonary vascular remodeling, but causes
      coronary vasodilation.

PMID- 29351412
TI  - Expression of CTGF/CCN2 in response to LPA is stimulated by fibrotic
      extracellular matrix via the integrin/FAK axis.
AB  - Fibrosis is a common feature of several chronic diseases and is characterized by
      exacerbated accumulation of ECM. An understanding of the cellular and molecular
      mechanisms involved in the development of this condition is crucial for designing
      efficient treatments for those pathologies. Connective tissue growth factor
      (CTGF/CCN2) is a pleiotropic protein with strong profibrotic activity. In this
      report, we present experimental evidence showing that ECM stimulates the
      synthesis of CTGF in response to lysophosphatidic acid (LPA).The integrin/focal
      adhesion kinase (FAK) signaling pathway mediates this effect, since CTGF
      expression is abolished by the use of the Arg-Gly-Asp-Ser peptide and also by an
      inhibitor of FAK autophosphorylation at tyrosine 397. Cilengitide, a specific
      inhibitor of alphav integrins, inhibits the expression of CTGF mediated by LPA or
      transforming growth factor beta1. We show that ECM obtained from decellularized
      myofibroblast cultures or derived from activated fibroblasts from muscles of the
      Duchenne muscular dystrophy mouse model ( mdx) induces the expression of CTGF.
      This effect is dependent on FAK phosphorylation in response to its activation by
      integrin. We also found that the fibrotic ECM inhibits skeletal muscle
      differentiation. This novel regulatory mechanism of CTGF expression could be
      acting as a positive profibrotic feedback between the ECM and CTGF, revealing a
      novel concept in the control of fibrosis under chronic damage.

PMID- 29351411
TI  - Disruption of the lens circulation causes calcium accumulation and precipitates
      in connexin mutant mice.
AB  - The lens is an avascular organ whose function and survival depend on an internal
      circulation system. Cx46fs380 mice model a human autosomal dominant cataract
      caused by a mutant lens connexin. In these mice, fiber cell connexin levels and
      gap junction coupling are severely decreased. The present studies were conducted
      to examine components of the lens circulation system that might be altered and
      contribute to the pathogenesis of cataracts. Lenses from wild-type mice and
      Cx46fs380 heterozygotes and homozygotes were studied at 2 months of age.
      Cx46fs380-expressing lens fiber cells were depolarized. Cx46fs380 lenses had
      increased intracellular hydrostatic pressure and concentrations of Na+ and Ca2+.
      The activity of epithelial Na+-K+-ATPase was decreased in Cx46fs380 lenses. All
      of these changes were more severe in homozygous than in heterozygous Cx46fs380
      lenses. Cx46fs380 cataracts were stained by Alizarin red, a dye used to detect
      insoluble Ca2+. These data suggest that the lens internal circulation was
      disrupted by expression of Cx46fs380, leading to several consequences including
      accumulation of Ca2+ to levels so high that precipitates formed. Similar Ca2+
      containing precipitates may contribute to cataract formation due to other genetic
      or acquired etiologies.

PMID- 29351413
TI  - Mitochondrial content is preserved throughout disease progression in the mdx
      mouse model of Duchenne muscular dystrophy, regardless of taurine
      supplementation.
AB  - Mitochondrial dysfunction is a pathological feature of Duchenne muscular
      dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterized by
      progressive muscle wasting and weakness. Mitochondria are a source of cellular
      ATP involved in Ca2+ regulation and apoptotic signaling. Ameliorating aberrant
      mitochondrial function has therapeutic potential for reducing DMD disease
      severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28 days,
      which stabilizes after 8 wk. The amino acid taurine is implicated in
      mitochondrial health and function, with endogenous concentrations low when
      measured during the cycle of peak muscle damage in mdx mice. Using whole soleus
      and extensor digitorum longus (EDL) muscle homogenates from 28- and 70-day mdx
      mice, we found that there was no change in native state mitochondrial complexes
      using blue native-PAGE. NADH:ubiquinone oxidotreductase subunit-A9 (NDUFA9)
      protein abundance was lower in soleus muscle of 28- and 70-day mdx mice and EDL
      muscle of 70-day mdx mice compared with same muscles in WT (C57/BL10ScSn)
      animals. There were age-dependent increases in both NDUFA9 protein abundance and
      citrate synthase activity in soleus muscles of mdx and wild-type mice. There was
      no change in abundances of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and
      mitochondrial dynamics protein 49 (MiD49). Taurine administration essentially did
      not affect any measurements of mitochondria. Collectively, these findings suggest
      mitochondrial content and dynamics are not reduced in the mdx mouse regardless of
      disease severity. We also elucidate that taurine affords no significant benefit
      to mitochondrial content or dynamics in the mdx mouse at either 28 or 70 days.

PMID- 29351414
TI  - The murine choroid plexus epithelium expresses the 2Cl-/H+ exchanger ClC-7 and
      Na+/H+ exchanger NHE6 in the luminal membrane domain.
AB  - The choroid plexus epithelium within the brain ventricles secretes the majority
      of the cerebrospinal fluid (CSF). The luminal Na+-K+-ATPase acts in concert with
      a host of other transport proteins to mediate efficient fluid secretion across
      the epithelium. The CSF contains little protein buffer, but the pH value seems
      nonetheless maintained within narrow limits, even when faced with acid-base
      challenges. The involvement of choroid plexus acid-base transporters in CSF pH
      regulation is highlighted by the expression of several acid-base transporters in
      the epithelium. The aim of the present study was to identify novel acid-base
      transporters expressed in the luminal membrane of the choroid plexus epithelium
      to pave the way for systematic investigations of each candidate transporter in
      the regulation of CSF pH. Mass spectrometry analysis of proteins from epithelial
      cells isolated by fluorescence-activated cell sorting identified the Cl-/H+
      exchangers ClC-3, -4, -5, and -7 in addition to known choroid plexus acid-base
      transporters. RT-PCR on FACS isolated epithelial cells confirmed the expression
      of the corresponding mRNAs, as well as Na+/H+ exchanger NHE6 mRNA. Both NHE6 and
      ClC-7 were immunolocalized to the luminal plasma membrane domain of the choroid
      plexus epithelial cells. Dynamic imaging of intracellular pH and membrane
      potential changes in isolated choroid plexus epithelial cells demonstrated Cl-
      gradient-driven changes in intracellular pH and membrane potential that are
      consistent with Cl-/H+ exchange. In conclusion, we have detected for the first
      time NHE6 and ClC-7 in the choroid plexus, which are potentially involved in pH
      regulation of the CSF.

PMID- 29351415
TI  - AMP-activated protein kinase and adenosine are both metabolic modulators that
      regulate chloride secretion in the shark rectal gland ( Squalus acanthias).
AB  - The production of endogenous adenosine during secretagogue stimulation of CFTR
      leads to feedback inhibition limiting further chloride secretion in the rectal
      gland of the dogfish shark (Squalus acanthias). In the present study, we examined
      the role of AMP-kinase (AMPK) as an energy sensor also modulating chloride
      secretion through CFTR. We found that glands perfused with forskolin and
      isobutylmethylxanthine (F + I), potent stimulators of chloride secretion in this
      ancient model, caused significant phosphorylation of the catalytic subunit Thr172
      of AMPK. These findings indicate that AMPK is activated during energy-requiring
      stimulated chloride secretion. In molecular studies, we confirmed that the
      activating Thr172 site is indeed present in the alpha-catalytic subunit of AMPK
      in this ancient gland, which reveals striking homology to AMPKalpha subunits
      sequenced in other vertebrates. When perfused rectal glands stimulated with F + I
      were subjected to severe hypoxic stress or perfused with pharmacologic inhibitors
      of metabolism (FCCP or oligomycin), phosphorylation of AMPK Thr172 was further
      increased and chloride secretion was dramatically diminished. The pharmacologic
      activation of AMPK with AICAR-inhibited chloride secretion, as measured by short
      circuit current, when applied to the apical side of shark rectal gland monolayers
      in primary culture. These results indicate that that activated AMPK, similar to
      adenosine, transmits an inhibitory signal from metabolism, that limits chloride
      secretion in the shark rectal gland.

PMID- 29351416
TI  - Acute and chronic resistance training downregulates select LINE-1 retrotransposon
      activity markers in human skeletal muscle.
AB  - Herein, we examined if acute or chronic resistance exercise affected markers of
      skeletal muscle long interspersed nuclear element-1 (LINE-1) retrotransposon
      activity. In study 1, 10 resistance-trained college-aged men performed three
      consecutive daily back squat sessions, and vastus lateralis biopsies were taken
      before (Pre), 2 h following session 1 (Post1), and 3 days following session 3
      (Post2). In study 2, 13 untrained college-aged men performed a full-body
      resistance training program (3 days/wk), and vastus lateralis biopsies were taken
      before ( week 0) and ~72 h following training cessation ( week 12). In study 1,
      LINE-1 mRNA decreased 42-48% at Post1 and 2 ( P < 0.05), and reverse
      transcriptase (RT) activity trended downward at Post2 (-37%, P = 0.067). In study
      2, LINE-1 mRNA trended downward at week 12 (-17%, P = 0.056) while LINE-1
      promoter methylation increased (+142%, P = 0.041). Open reading frame (ORF)2p
      protein expression (-24%, P = 0.059) and RT activity (-26%, P = 0.063) also
      trended downward by week 12. Additionally, changes in RT activity versus
      satellite cell number were inversely associated ( r = -0.725, P = 0.008). Follow
      up in vitro experiments demonstrated that 48-h treatments with lower doses (1 MUM
      and 10 MUM) of efavirenz and nevirapine (non-nucleoside RT inhibitors) increased
      myoblast proliferation ( P < 0.05). However, we observed a paradoxical decrease
      in myoblast proliferation with higher doses (50 MUM) of efavirenz and
      delavirdine. This is the first report suggesting that resistance exercise
      downregulates markers of skeletal muscle LINE-1 activity. Given our discordant in
      vitro findings, future research is needed to thoroughly assess whether LINE-1
      mediated RT activity enhances or blunts myoblast, or primary satellite cell,
      proliferative capacity.

PMID- 29351417
TI  - Zinc regulates vascular endothelial cell activity through zinc-sensing receptor
      ZnR/GPR39.
AB  - Zn2+ is an essential element for cell survival/growth, and its deficiency is
      linked to many disorders. Extracellular Zn2+ concentration changes participate in
      modulating fundamental cellular processes such as proliferation, secretion, ion
      transport, and cell signal transduction in a mechanism that is not well
      understood. Here, we hypothesize that the Zn2+-sensing receptor ZnR/G protein
      coupled receptor 39 (GPR39), found in tissues where dynamic Zn2+ homeostasis
      takes place, enables extracellular Zn2+ to trigger intracellular signaling
      pathways regulating key cell functions in vascular cells. Thus, we investigated
      how extracellular Zn2+ regulates cell viability, proliferation, motility,
      angiogenesis, vascular tone, and inflammation through ZnR/GPR39 in endothelial
      cells. Knockdown of GPR39 through siRNA largely abolished Zn2+-triggered cellular
      activity changes, Ca2+ responses, as well as the downstream activation of Galphaq
      PLC pathways. Extracellular Zn2+ promoted vascular cell survival/growth through
      activation of cAMP and Akt as well as overexpressing of platelet-derived growth
      factor-alpha receptor and vascular endothelial growth factor A. It also enhanced
      cell adhesion and mobility, endothelial tubule formation, and cytoskeletal
      reorganization. Such effects from extracellular Zn2+ were not observed in GPR39-/
      endothelial cells. Zn2+ also regulated inflammation-related key molecules such
      as heme oxygenase-1, selectin L, IL-10, and platelet endothelial cell adhesion
      molecule 1, as well as vascular tone-related prostaglandin I2 synthase and nitric
      oxide synthase-3. In sum, extracellular Zn2+ regulates endothelial cell activity
      in a ZnR/GPR39-dependent manner and through the downstream Galphaq-PLC pathways.
      Thus, ZnR/GPR39 may be a therapeutic target for regulating endothelial activity.

PMID- 29351419
TI  - Maternal nutrient restriction in guinea pigs as an animal model for studying
      growth-restricted offspring with postnatal catch-up growth.
AB  - We determined the impact of moderate maternal nutrient restriction (MNR) in
      guinea pigs with fetal growth restriction (FGR) on offspring body and organ
      weights, hypothesizing that FGR-MNR animals will show catch-up growth but with
      organ-specific differences. Guinea pig sows were fed ad libitum (Control) or 70%
      of the control diet from 4 weeks preconception, switching to 90% at midpregnancy
      (MNR). Control newborns >95 g [appropriate for gestational age (AGA); n = 37] and
      MNR newborns <85 g (FGR; n = 37) were monitored until neonatal (~25 days) or
      adult (~110 days) necropsy. Birth weights and body/organ weights at necropsy were
      used to calculate absolute and fractional growth rates (FRs). FGR-MNR birth
      weights were decreased ~32% compared with the AGA-Controls. FGR-MNR neonatal
      whole body FRs were increased ~36% compared with Controls indicating catch-up
      growth, with values negatively correlated to birth weights indicating the degree
      of FGR leads to greater catch-up growth. However, the increase in organ FRs in
      the FGR-MNR neonates compared with Controls was variable, being similar for the
      brain and kidneys indicating comparable catch-up growth to that of the whole body
      and twofold increased for the liver but negligible for the heart indicating
      markedly increased and absent catch-up growth, respectively. While FGR-MNR body
      and organ weights were unchanged from the AGA-Controls by adulthood, whole body
      growth rates were increased. These findings confirm early catch-up growth in FGR
      MNR guinea pigs but with organ-specific differences and enhanced growth rates by
      adulthood, which are likely to have implications for structural alterations and
      disease risk in later life.

PMID- 29351418
TI  - Red blood cell antibody-induced anemia causes differential degrees of tissue
      hypoxia in kidney and brain.
AB  - Moderate anemia is associated with increased mortality and morbidity, including
      acute kidney injury (AKI), in surgical patients. A red blood cell (RBC)-specific
      antibody model was utilized to determine whether moderate subacute anemia could
      result in tissue hypoxia as a potential mechanism of injury. Cardiovascular and
      hypoxic cellular responses were measured in transgenic mice capable of expressing
      hypoxia-inducible factor-1alpha (HIF-1alpha)/luciferase activity in vivo.
      Antibody-mediated anemia was associated with mild intravascular hemolysis (6 h)
      and splenic RBC sequestration ( day 4), resulting in a nadir hemoglobin
      concentration of 89 +/- 13 g/l on day 4. At this time point, renal tissue oxygen
      tension (PtO2) was decreased in anemic mice relative to controls (13.1 +/- 4.3
      vs. 20.8 +/- 3.7 mmHg, P < 0.001). Renal tissue hypoxia was associated with an
      increase in HIF/luciferase expression in vivo ( P = 0.04) and a 20-fold relative
      increase in renal erythropoietin mRNA transcription ( P < 0.001) but no increase
      in renal blood flow ( P = 0.67). By contrast, brain PtO2 was maintained in anemic
      mice relative to controls (22.7 +/- 5.2 vs. 23.4 +/- 9.8 mmHg, P = 0.59) in part
      because of an increase in internal carotid artery blood flow (80%, P < 0.001) and
      preserved cerebrovascular reactivity. Despite these adaptive changes, an increase
      in brain HIF-dependent mRNA levels was observed (erythropoietin: P < 0.001; heme
      oxygenase-1: P = 0.01), providing evidence for subtle cerebral tissue hypoxia in
      anemic mice. These data demonstrate that moderate subacute anemia causes
      significant renal tissue hypoxia, whereas adaptive cerebrovascular responses
      limit the degree of cerebral tissue hypoxia. Further studies are required to
      assess whether hypoxia is a mechanism for acute kidney injury associated with
      anemia.

PMID- 29351420
TI  - Fourth ventricular thyrotropin induces satiety and increases body temperature in
      rats.
AB  - Besides its well-known action to stimulate thyroid hormone release, thyrotropin
      mRNA is expressed within the brain, and thyrotropin and its receptor have been
      shown to be present in brain areas that control feeding and gastrointestinal
      function. Here, the hypothesis that thyrotropin acts on receptors in the
      hindbrain to alter food intake and/or gastric function was tested. Fourth
      ventricular injections of thyrotropin (0.06, 0.60, and 6.00 ug) were given to
      rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle.
      Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest
      dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In
      contrast, subcutaneous administration of corresponding thyrotropin doses had no
      effect on nutrient intake. The highest effective dose of fourth ventricular
      thyrotropin (6 ug) did not produce a conditioned flavor avoidance in a
      standardized two-bottle test, nor did it affect water intake or gastric emptying
      of glucose. Thyrotropin injected in the fourth ventricle produced a small but
      significant increase in rectal temperature and lowered plasma levels of tri
      iodothyronin but did not affect plasma levels of thyroxine. In addition, there
      was a tendency toward a reduction in blood glucose 2 h after fourth ventricular
      thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin
      specifically inhibits food intake, increases core temperature, and lowers plasma
      levels of tri-iodothyronin but does not affect gastromotor function.

PMID- 29351421
TI  - Increased insulin clearance in mice with double deletion of glucagon-like peptide
      1 and glucose-dependent insulinotropic polypeptide receptors.
AB  - To establish whether incretin hormones affect insulin clearance, the aim of this
      study was to assess insulin clearance in mice with genetic deletion of receptors
      for both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic
      polypeptide (GIP), so called double incretin receptor knockout mice (DIRKO).
      DIRKO ( n = 31) and wild-type (WT) C57BL6J mice ( n = 45) were intravenously
      injected with d-glucose (0.35 g/kg). Blood was sampled for 50 min and assayed for
      glucose, insulin, and C-peptide. Data were modeled to calculate insulin
      clearance; C-peptide kinetics was established after human C-peptide injection.
      Assessment of C-peptide kinetics revealed that C-peptide clearance was 1.66 +/-
      0.10 10-3 1/min. After intravenous glucose administration, insulin clearance
      during first phase insulin secretion was markedly higher in DIRKO than in WT mice
      (0.68 +/- 0.06 10-3 l/min in DIRKO mice vs. 0.54 +/- 0.03 10-3 1/min in WT mice,
      P = 0.02). In contrast, there was no difference between the two groups in insulin
      clearance during second phase insulin secretion ( P = 0.18). In conclusion, this
      study evaluated C-peptide kinetics in the mouse and exploited a mathematical
      model to estimate insulin clearance. Results showed that DIRKO mice have higher
      insulin clearance than WT mice, following intravenous injection of glucose. This
      suggests that incretin hormones reduce insulin clearance at physiological,
      nonstimulated levels.

PMID- 29351424
TI  - Clocking skin sodium.

PMID- 29351422
TI  - Body mass-specific Na+-K+-ATPase activity in the medullary thick ascending limb:
      implications for species-dependent urine concentrating mechanisms.
AB  - In general, the mammalian whole body mass-specific metabolic rate correlates
      positively with maximal urine concentration (Umax) irrespective of whether or not
      the species have adapted to arid or mesic habitat. Accordingly, we hypothesized
      that the thick ascending limb (TAL) of a rodent with markedly higher whole body
      mass-specific metabolism than rat exhibits a substantially higher TAL metabolic
      rate as estimated by Na+-K+-ATPase activity and Na+-K+-ATPase alpha1-gene and
      protein expression. The kangaroo rat inner stripe of the outer medulla exhibits
      significantly higher mean Na+-K+-ATPase activity (~70%) compared with two rat
      strains (Sprague-Dawley and Munich-Wistar), extending prior studies showing rat
      activity exceeds rabbit. Furthermore, higher expression of Na+-K+-ATPase alpha1
      protein (~4- to 6-fold) and mRNA (~13-fold) and higher TAL mitochondrial volume
      density (~20%) occur in the kangaroo rat compared with both rat strains. Rat TAL
      Na+-K+-ATPase alpha1-protein expression is relatively unaffected by body
      hydration status or, shown previously, by dietary Na+, arguing against
      confounding effects from two unavoidably dissimilar diets: grain-based diet
      without water (kangaroo rat) or grain-based diet with water (rat). We conclude
      that higher TAL Na+-K+-ATPase activity contributes to relationships between whole
      body mass-specific metabolic rate and high Umax. More vigorous TAL Na+-K+-ATPase
      activity in kangaroo rat than rat may contribute to its steeper Na+ and urea
      axial concentration gradients, adding support to a revised model of the urine
      concentrating mechanism, which hypothesizes a leading role for vigorous active
      transport of NaCl, rather than countercurrent multiplication, in generating the
      outer medullary axial osmotic gradient.

PMID- 29351425
TI  - Source of dietary sucrose influences development of leptin resistance in male and
      female rats.
AB  - Male rats offered 30% sucrose solution in addition to chow develop leptin
      resistance without an increase in energy intake or body fat. This study tested
      whether the leptin resistance was dependent on the physical form of the sucrose.
      Sprague-Dawley rats were offered a sucrose-free (NS) diet, a 66.6% of energy as
      sucrose (HS) diet, or the NS diet + 30% sucrose solution (LS). Sucrose intake of
      LS rats equaled that of HS rats, but total carbohydrate intake exceeded that of
      HS rats. After 33 days, male and female LS rats were resistant to the inhibitory
      effect of peripherally administered leptin on food intake. LS rats drank small,
      frequent meals of sucrose during light and dark periods, whereas HS rats consumed
      more meals during the dark than the light period and remained responsive to
      leptin. Diet did not affect daily energy intake or insulin sensitivity. There was
      a small increase in body fat in the female rats. Leptin sensitivity was restored
      within 5 days of withdrawal from sucrose in male LS rats. This rapid reversal
      suggested that leptin resistance was associated with the metabolic impact of
      drinking sucrose. An experiment was carried out to test whether activity of the
      hexosamine biosynthetic pathway and glycation of leptin signaling proteins were
      increased in LS rats, but the results were equivocal. A final experiment
      determined that female LS rats were leptin-resistant within 18 days of access to
      sucrose solution and that the small, but significant, increase in body fat was
      associated with increased adipocyte glucose utilization and insulin
      responsiveness, which may have been secondary to adipocyte leptin resistance.

PMID- 29351423
TI  - Role of TRPV1 in acupuncture modulation of reflex excitatory cardiovascular
      responses.
AB  - We have shown that acupuncture, including manual and electroacupuncture (MA and
      EA), at the P5-6 acupoints stimulates afferent fibers in the median nerve (MN) to
      modulate sympathoexcitatory cardiovascular reflexes through central regulation of
      autonomic function. However, the mechanisms underlying acupuncture activation of
      these sensory afferent nerves and their cell bodies in the dorsal root ganglia
      (DRG) are unclear. Transient receptor potential vanilloid type 1 (TRPV1) is
      present in sensory nerve fibers distributed in the general region of acupoints
      like ST36 and BL 40 located in the hindlimb. However, the contribution of TRPV1
      to activation of sensory nerves by acupuncture, leading to modulation of pressor
      responses, has not been studied. We hypothesized that TRPV1 participates in
      acupuncture's activation of sensory afferents and their associated cell bodies in
      the DRG to modulate pressor reflexes. Local injection of iodoresiniferatoxin
      (Iodo-RTX; a selective TRPV1 antagonist), but not 5% DMSO (vehicle), into the P6
      acupoint on the forelimb reversed the MA's inhibition of pressor reflexes induced
      by gastric distension (GD). Conversely, inhibition of GD-induced
      sympathoexcitatory responses by EA at P5-6 was unchanged after administration of
      Iodo-RTX into P5-6. Single-unit activity of Group III or IV bimodal afferents
      sensitive to both mechanical and capsaicin stimuli responded to MA stimulation at
      P6. MA-evoked activity was attenuated significantly ( P < 0.05) by local
      administration of Iodo-RTX ( n = 12) but not by 5% DMSO ( n = 12) into the region
      of the P6 acupoint in rats. Administration of Iodo-RTX into P5-6 did not reduce
      bimodal afferent activity evoked by EA stimulation ( n = 8). Finally, MA at P6
      and EA at P5-6 induced phosphorylation of extracellular signal-regulated kinases
      (ERK; an intracellular signaling messenger involved in cellular excitation) in
      DRG neurons located at C7-8 spinal levels receiving MN inputs. After TRPV1 was
      knocked down in the DRG at these spinal levels with intrathecal injection of
      TRPV1-siRNA, expression of phosphorylated ERK in the DRG neuron was reduced in MA
      treated, but not EA-treated animals. These data suggest that TRPV1 in Group III
      and IV bimodal sensory afferent nerves contributes to acupuncture inhibition of
      reflex increases in blood pressure and specifically plays an important role
      during MA but not EA.

PMID- 29351426
TI  - Effects of heat and cold on health, with special reference to Finnish sauna
      bathing.
AB  - Environmental stress such as extremely warm or cold temperature is often
      considered a challenge to human health and body homeostasis. However, the human
      body can adapt relatively well to heat and cold environments, and recent studies
      have also elucidated that particularly heat stress might be even highly
      beneficial for human health. Consequently, the aim of the present brief review is
      first to discuss general cardiovascular and other responses to acute heat stress,
      followed by a review of beneficial effects of Finnish sauna bathing on general
      and cardiovascular health and mortality as well as dementia and Alzheimer's
      disease risk. Plausible mechanisms included are improved endothelial and
      microvascular function, reduced blood pressure and arterial stiffness, and
      possibly increased angiogenesis in humans, which are likely to mediate the health
      benefits of sauna bathing. In addition to heat exposure with physiological
      adaptations, cold stress-induced physiological responses and brown fat activation
      on health are also discussed. This is important to take into consideration, as
      sauna bathing is frequently associated with cooling periods in cold(er)
      environments, but their combination remains poorly investigated. We finally
      propose, therefore, that possible additive effects of heat- and cold-stress
      induced adaptations and effects on health would be worthy of further
      investigation.

PMID- 29351427
TI  - Role of PTP1B in POMC neurons during chronic high-fat diet: sex differences in
      regulation of liver lipids and glucose tolerance.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of leptin
      receptor signaling and may contribute to leptin resistance in diet-induced
      obesity. Although PTP1B inhibition has been suggested as a potential weight loss
      therapy, the role of specific neuronal PTP1B signaling in cardiovascular and
      metabolic regulation and the importance of sex differences in this regulation are
      still unclear. In this study, we investigated the impact of proopiomelanocortin
      (POMC) neuronal PTP1B deficiency in cardiometabolic regulation in male and female
      mice fed a high-fat diet (HFD). When compared with control mice (PTP1B
      flox/flox), male and female mice deficient in POMC neuronal PTP1B (PTP1B
      flox/flox/POMC-Cre) had attenuated body weight gain (males: -18%; females: -16%)
      and fat mass (males: -33%; female: -29%) in response to HFD. Glucose tolerance
      was improved by 40%, and liver lipid accumulation was reduced by 40% in
      PTP1B/POMC-Cre males but not in females. When compared with control mice,
      deficiency of POMC neuronal PTP1B did not alter mean arterial pressure (MAP) in
      male or female mice (males: 112 +/- 1 vs. 112 +/- 1 mmHg in controls; females:
      106 +/- 3 vs. 109 +/- 3 mmHg in controls). Deficiency of POMC neuronal PTP1B also
      did not alter MAP response to acute stress in males or females compared with
      control mice (males: Delta32 +/- 0 vs. Delta29 +/- 4 mmHg; females: Delta22 +/- 2
      vs. Delta27 +/- 4 mmHg). These data demonstrate that POMC-specific PTP1B
      deficiency improved glucose tolerance and attenuated diet-induced fatty liver
      only in male mice and attenuated weight gain in males and females but did not
      enhance the MAP and HR responses to a HFD or to acute stress.

PMID- 29351428
TI  - Control of appetite, blood glucose, and blood pressure during melanocortin-4
      receptor activation in normoglycemic and diabetic NPY-deficient mice.
AB  - Although central melanocortin 4 receptor (MC4R) blockade abolishes the central
      nervous system (CNS)-mediated anorexogenic, antidiabetic, and cardiovascular
      actions of leptin, chronic MC4R stimulation fails to completely mimic the effects
      of leptin. Because neuropeptide Y (NPY) and MC4R exert opposite effects on
      cardiovascular and metabolic functions, we tested the role of NPY in offsetting
      the long-term actions of MC4R activation. Wild-type (WT) and NPY-deficient (NPY-/
      ) mice were implanted with telemetry probes for measuring mean arterial pressure
      (MAP) and heart rate (HR) 24 h/day. After the mice recovered from surgery and
      stable baseline measurements, the MC3/4R agonist melanotan II (MTII, 120 MUg.kg
      1.day-1 iv) was infused for 7 days followed by a recovery period. No major
      differences between groups were observed at baseline except for slightly higher
      food intake and HR in NPY-/- mice (4.3 +/- 0.2 vs. 3.4 +/- 0.2 g/day and 567 +/-
      14 vs. 522 +/- 13 beats/min). Chronic MTII infusion reduced food intake in both
      groups while causing transient increases in MAP and HR only in WT mice (peaks of
      11 +/- 3 mmHg and 126 +/- 13 beats/min). To examine whether NPY deficiency would
      amplify the antidiabetic effects of MC4R activation, diabetes was induced with
      streptozotocin (STZ) 1 wk before baseline measurements were taken, and the same
      experimental protocol was followed. In WT and NPY-/- mice, STZ-induced diabetes
      led to similar hyperphagia, hyperglycemia, and weight loss, which were not
      reversed by chronic MTII treatment. Our results demonstrate that chronic MC4R
      activation, even in NPY-deficient mice, does not mimic chronic antidiabetic,
      cardiovascular, or metabolic actions of leptin, and that NPY is not essential for
      hyperphagia or cardiovascular changes associated with diabetes.

PMID- 29351430
TI  - Dynamic changes in nitric oxide synthase expression are involved in seawater
      acclimation of rainbow trout Oncorhynchus mykiss.
AB  - Recent research has shown that nitric oxide (NO) produced by nitric oxide
      synthases (NOS) is an inhibitor of ion transporter activity and a modulator of
      epithelial ion transport in fish, but little is known on changes in the NOS/NO
      system during osmotic stress. We hypothesized that the NOS/NO system responds to
      salinity changes as an integrated part of the acclimation process. Expression and
      localization of nos1/Nos1 and nos2/Nos2 were investigated in gill, kidney, and
      intestine of freshwater (FW)- and seawater (SW)-transferred trout using
      quantitative PCR, Western blotting, and immunohistochemistry, along with
      expressional changes of major ion transporters in the gill. The classical
      branchial ion transporters showed expected expressional changes upon SW transfer,
      there among a rapid decrease in Slc26a6 mRNA, coding a branchial Cl-/[Formula:
      see text] exchanger. There was a major downregulation of nos1/ nos2/Nos2
      expression in the gill during SW acclimation. A significant decrease in plasma
      nitrite supported an overall decreased Nos activity and NO production. In the
      middle intestine, Nos1 was upregulated during SW acclimation, whereas no changes
      in nos/Nos expression were observed in the posterior intestine and the kidney.
      Nos1 was localized along the longitudinal axis of the gill filament, beneath
      smooth muscle fibers of the intestine wall and in blood vessel walls of the
      kidney. Nos2 was localized within the epithelium adjacent to the gill filament
      axis and in hematopoietic tissues of the kidney. We conclude that downregulation
      of branchial NOS is integrated to the SW acclimation process likely to avoid the
      inhibitory effects of NO on active ion extrusion.

PMID- 29351429
TI  - Removal of interscapular brown adipose tissue increases aortic stiffness despite
      normal systemic glucose metabolism in mice.
AB  - Brown adipose tissue (BAT) is considered protective against obesity and related
      cardiometabolic dysfunction. Indeed, activation of BAT improves glucose
      homeostasis and attenuates cardiovascular disease development. However, whether a
      reduction in BAT mass perturbs metabolic function and increases risk for
      cardiovascular disease remains largely unknown. To address this question,
      C57BL/6J male mice underwent a sham procedure or surgical bilateral excision of
      interscapular BAT (iBATx) and were fed a normal chow or a Western diet for 18 wk,
      creating four groups ( n = 10/group). Mice were housed at 25 degrees C. As
      expected, the Western diet increased final body weight and adiposity; however,
      contrary to our hypothesis, iBATx did not potentiate adiposity independent of
      diet. Furthermore, iBATx did not affect indexes of glycemic control (HbA1c,
      fasting glucose and insulin, and glucose area under the curve during a glucose
      tolerance test) and produced minimal-to-no effects on lipid homeostasis. The
      absence of metabolic disturbances with iBATx was not attributed to regrowth of
      iBAT or a "browning" or proliferative compensatory response of other BAT depots.
      Notably, iBATx caused an increase in aortic stiffness in normal chow-fed mice
      only, which was associated with an increase in aortic uncoupling protein-1.
      Collectively, we demonstrated that, at 25 degrees C (i.e., limited thermal stress
      conditions), a substantial reduction in BAT mass via iBATx does not disrupt
      systemic glucose metabolism, challenging the current dogma that preservation of
      BAT is obligatory for optimal metabolic function. However, iBATx caused aortic
      stiffening in lean mice, hence supporting the existence of an interplay between
      iBAT and aortic stiffness, independent of alterations in glucose homeostasis.

PMID- 29351431
TI  - Feasibility of phase-contrast cine magnetic resonance imaging for measuring blood
      flow in the sheep fetus.
AB  - Phase-contrast cine MRI (PC-MRI) is the gold-standard non-invasive technique for
      measuring vessel blood flow and has previously been applied in the human fetal
      circulation. We aimed to assess the feasibility of using PC-MRI to define the
      distribution of the fetal circulation in sheep. Fetuses were catheterized at 119
      120 days gestation (term, 150 days) and underwent MRI at 123 days gestation under
      isoflurane anesthesia, ventilated at a FiO2 of 1.0. PC-MRI was performed using a
      fetal arterial blood pressure catheter signal for cardiac triggering. Blood flows
      were measured in the major fetal vessels, including the main pulmonary artery,
      ascending and descending aorta, superior vena cava, ductus arteriosus, left and
      right pulmonary arteries, umbilical vein, ductus venosus, and common carotid
      artery; and were indexed to estimated fetal weight. The combined ventricular
      output, pulmonary blood flow and flow across the foramen ovale were calculated
      from vessel flows. Intra-observer, inter-observer agreement and reproducibility
      were assessed. Blood flow measurements were successfully obtained in 61 out of 74
      vessels (82.4%) interrogated in 9 fetuses. There was good intra-observer
      (R=0.998, P<0.0001; ICC=0.997) and inter-observer agreement (R=0.996, P<0.0001;
      ICC=0.996). Repeated MRI measurements showed good reproducibility (R=0.989,
      P=0.0002; ICC=0.990). We conclude that PC-MRI using fetal catheters for gating
      triggers is feasible in the major vessels of late gestation fetal sheep. This
      approach may provide a useful new tool for assessing the circulatory
      characteristics of fetal sheep models of human disease, including fetal growth
      restriction and congenital heart disease.

PMID- 29351433
TI  - beta-Nitrostyrene derivatives attenuate LPS-mediated acute lung injury via the
      inhibition of neutrophil-platelet interactions and NET release.
AB  - Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are
      high-mortality and life-threatening diseases that are associated with neutrophil
      activation and accumulation within lung tissue. Emerging evidence indicates that
      neutrophil-platelet aggregates (NPAs) at sites of injury increase acute
      inflammation and contribute to the development of ALI. Although numerous studies
      have increased our understanding of the pathophysiology of ALI, there is still a
      lack of innovative and useful treatments that reduce mortality, emphasizing that
      there is an urgent need for novel treatment strategies. In this study, a new
      series of small compounds of beta-nitrostyrene derivatives (BNSDs) were
      synthesized, and their anti-inflammatory bioactivities on neutrophils and
      platelets were evaluated. The new small compound C7 modulates neutrophil function
      by inhibiting superoxide generation and elastase release. Compound C7 elicits
      protective effects on LPS-induced paw edema and acute lung injury via the
      inhibition of neutrophil accumulation, proinflammatory mediator release, platelet
      aggregation, myeloperoxidase activity, and neutrophil extracellular trap (NET)
      release. NET formation was identified as the bridge for the critical interactions
      between neutrophils and platelets by confocal microscopy and flow cytometry. This
      research provides new insights for elucidating the complicated regulation of
      neutrophils and platelets in ALI and sheds further light on future drug
      development strategies for ALI/ARDS and acute inflammatory diseases.

PMID- 29351432
TI  - Diurnal pattern in skin Na+ and water content is associated with salt-sensitive
      hypertension in ETB receptor-deficient rats.
AB  - Impairment in the ability of the skin to properly store Na+ nonosmotically
      (without water) has recently been hypothesized as contributing to salt-sensitive
      hypertension. Our laboratory has shown that endothelial production of endothelin
      1 (ET-1) is crucial to skin Na+ handling. Furthermore, it is well established
      that loss of endothelin type B receptor (ETB) receptor function impairs Na+
      excretion by the kidney. Thus we hypothesized that rats lacking functional ETB
      receptors (ETB-def) will have a reduced capacity of the skin to store Na+ during
      chronic high-salt (HS) intake. We observed that ETB-def rats exhibited salt
      sensitive hypertension with an approximate doubling in the diurnal amplitude of
      mean arterial pressure compared with genetic control rats on a HS diet. Two weeks
      of HS diet significantly increased skin Na+ content relative to water; however,
      there was no significant difference between control and ETB-def rats.
      Interestingly, HS intake led to a 19% increase in skin Na+ and 16% increase in
      water content (relative to dry wt.) during the active phase (zeitgeber time 16)
      versus inactive phase (zeitgeber time 4, P < 0.05) in ETB-def rats. There was no
      significant circadian variation in total skin Na+ or water content of control
      rats fed normal or HS. These data indicate that ETB receptors have little
      influence on the ability to store Na+ nonosmotically in the skin during long-term
      HS intake but, rather, appear to regulate diurnal rhythms in skin Na+ content and
      circadian blood pressure rhythms associated with a HS diet.

PMID- 29351434
TI  - Cub domain-containing protein 1 negatively regulates TGF-beta signaling and
      myofibroblast differentiation.
AB  - Fibroblasts are thought to be the prime cell type for producing and secreting
      extracellular matrix (ECM) proteins in the connective tissue. The profibrotic
      cytokine transforming growth factor-beta1 (TGF-beta1) activates and
      transdifferentiates fibroblasts into alpha-smooth muscle actin (alpha-SMA)
      expressing myofibroblasts, which exhibit increased ECM secretion, in particular
      collagens. Little information, however, exists about cell-surface molecules on
      fibroblasts that mediate this transdifferentiation process. We recently
      identified, using unbiased cell-surface proteome analysis, Cub domain-containing
      protein 1 (CDCP1) to be strongly downregulated by TGF-beta1. CDCP1 is a
      transmembrane glycoprotein, the expression and role of which has not been
      investigated in lung fibroblasts to date. Here, we characterized, in detail, the
      effect of TGF-beta1 on CDCP1 expression and function, using immunofluorescence,
      FACS, immunoblotting, and siRNA-mediated knockdown of CDCP1. CDCP1 is present on
      interstitial fibroblasts, but not myofibroblasts, in the normal and idiopathic
      pulmonary fibrosis lung. In vitro, TGF-beta1 decreased CDCP1 expression in a time
      dependent manner by impacting mRNA and protein levels. Knockdown of CDCP1
      enhanced a TGF-beta1-mediated cell adhesion of fibroblasts. Importantly, CDCP1
      depleted cells displayed an enhanced expression of profibrotic markers, such as
      collagen V or alpha-SMA, which was found to be independent of TGF-beta1. Our data
      show, for the very first time that loss of CDCP1 contributes to fibroblast to
      myofibroblast differentiation via a potential negative feedback loop between
      CDCP1 expression and TGF-beta1 stimulation.

PMID- 29351436
TI  - Therapeutic attenuation of the epithelial sodium channel with a SPLUNC1-derived
      peptide in airway diseases.

PMID- 29351435
TI  - Effects of cigarette smoke on pulmonary endothelial cells.
AB  - Cigarette smoking is the leading cause of preventable disease and death in the
      United States. Cardiovascular comorbidities associated with both active and
      secondhand cigarette smoking indicate the vascular toxicity of smoke exposure.
      Growing evidence supports the injurious effect of cigarette smoke on pulmonary
      endothelial cells and the roles of endothelial cell injury in development of
      acute respiratory distress syndrome (ARDS), emphysema, and pulmonary
      hypertension. This review summarizes results from studies of humans, preclinical
      animal models, and cultured endothelial cells that document toxicities of
      cigarette smoke exposure on pulmonary endothelial cell functions, including
      barrier dysfunction, endothelial activation and inflammation, apoptosis, and
      vasoactive mediator production. The discussion is focused on effects of cigarette
      smoke-induced endothelial injury in the development of ARDS, emphysema, and
      vascular remodeling in chronic obstructive pulmonary disease.

PMID- 29351438
TI  - Systematic reviews of the literature: a better way of addressing basic science
      controversies.

PMID- 29351437
TI  - Metabolic reprogramming in the pathogenesis of chronic lung diseases, including
      BPD, COPD, and pulmonary fibrosis.
AB  - The metabolism of nutrient substrates, including glucose, glutamine, and fatty
      acids, provides acetyl-CoA for the tricarboxylic acid cycle to generate energy,
      as well as metabolites for the biosynthesis of biomolecules, including
      nucleotides, proteins, and lipids. It has been shown that metabolism of glucose,
      fatty acid, and glutamine plays important roles in modulating cellular
      proliferation, differentiation, apoptosis, autophagy, senescence, and
      inflammatory responses. All of these cellular processes contribute to the
      pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia,
      chronic obstructive pulmonary disease, and pulmonary fibrosis. Recent studies
      demonstrate that metabolic reprogramming occurs in patients with and animal
      models of chronic lung diseases, suggesting that metabolic dysregulation may
      participate in the pathogenesis and progression of these diseases. In this
      review, we briefly discuss the catabolic pathways for glucose, glutamine, and
      fatty acids, and focus on how metabolic reprogramming of these pathways impacts
      cellular functions and leads to the development of these chronic lung diseases.
      We also highlight how targeting metabolic pathways can be utilized in the
      prevention and treatment of these diseases.

PMID- 29351439
TI  - Role of reactive oxygen species and sulfide-quinone oxoreductase in hydrogen
      sulfide-induced contraction of rat pulmonary arteries.
AB  - Application of H2S ("sulfide") elicits a complex contraction in rat pulmonary
      arteries (PAs) comprising a small transient contraction (phase 1; Ph1) followed
      by relaxation and then a second, larger, and more sustained contraction (phase 2;
      Ph2). We investigated the mechanisms causing this response using isometric
      myography in rat second-order PAs, with Na2S as a sulfide donor. Both phases of
      contraction to 1,000 MUM Na2S were attenuated by the pan-PKC inhibitor Go6983 (3
      MUM) and by 50 MUM ryanodine; the Ca2+ channel blocker nifedipine (1 MUM) was
      without effect. Ph2 was attenuated by the mitochondrial complex III blocker
      myxothiazol (1 MUM), the NADPH oxidase (NOX) blocker VAS2870 (10 MUM), and the
      antioxidant TEMPOL (3 mM) but was unaffected by the complex I blocker rotenone (1
      MUM). The bath sulfide concentration, measured using an amperometric sensor,
      decreased rapidly following Na2S application, and the peak of Ph2 occurred when
      this had fallen to ~50 MUM. Sulfide caused a transient increase in NAD(P)H
      autofluorescence, the offset of which coincided with development of the Ph2
      contraction. Sulfide also caused a brief mitochondrial hyperpolarization
      (assessed using tetramethylrhodamine ethyl ester), followed immediately by
      depolarization and then a second more prolonged hyperpolarization, the onset of
      which was temporally correlated with the Ph2 contraction. Sulfide application to
      cultured PA smooth muscle cells increased reactive oxygen species (ROS)
      production (recorded using L012); this was absent when the mitochondrial
      flavoprotein sulfide-quinone oxoreductase (SQR) was knocked down using small
      interfering RNA. We propose that the Ph2 contraction is largely caused by SQR
      mediated sulfide metabolism, which, by donating electrons to ubiquinone,
      increases electron production by complex III and thereby ROS production.

PMID- 29351440
TI  - JQ1 is a potential therapeutic option for COPD patients with agrin
      overexpression.
AB  - Chronic obstructive pulmonary disease (COPD) is one of the leading causes of
      morbidity and death worldwide. It is characterized by chronic pulmonary
      inflammation and obstructed airflow from the lungs. To date, there is no
      effective treatment for COPD. The activation of the agrin (AGRN-YAP pathway can
      promote heart regeneration. Because agrin can induce only mild cardiomyocyte
      proliferation compared with ERBB2 pathway activation, it might exert pleiotropic
      effects, such as mitigation of innate inflammation, immune response, and
      fibrosis. Previously, we demonstrated that several common pathological gene
      regulatory programs such as innate inflammatory and profibrotic transcriptional
      networks were shared by COPD and heart failure. In this study, we show that agrin
      is inversely correlated with COPD development and progression and may exert its
      effects by suppressing innate inflammation and profibrotic signaling pathways.
      BET inhibitor JQ1, in line with our previous findings, is a promising therapeutic
      option in the treatment of patients with COPD. Nevertheless, wet laboratory
      experiments and clinical trials are needed before its application in clinical
      practice.

PMID- 29351441
TI  - Vx-809/Vx-770 treatment reduces inflammatory response to Pseudomonas aeruginosa
      in primary differentiated cystic fibrosis bronchial epithelial cells.
AB  - Cystic fibrosis patients exhibit chronic Pseudomonas aeruginosa respiratory
      infections and sustained proinflammatory state favoring lung tissue damage and
      remodeling, ultimately leading to respiratory failure. Loss of cystic fibrosis
      transmembrane conductance regulator (CFTR) function is associated with MAPK
      hyperactivation and increased cytokines expression, such as interleukin-8
      [chemoattractant chemokine (C-X-C motif) ligand 8 (CXCL8)]. Recently, new
      therapeutic strategies directly targeting the basic CFTR defect have been
      developed, and ORKAMBI (Vx-809/Vx-770 combination) is the only Food and Drug
      Administration-approved treatment for CF patients homozygous for the F508del
      mutation. Here we aimed to determine the effect of the Vx-809/Vx-770 combination
      on the induction of the inflammatory response by fully differentiated primary
      bronchial epithelial cell cultures from CF patients carrying F508del mutations,
      following exposure to P. aeruginosa exoproducts. Our data unveiled that CFTR
      functional rescue with Vx-809/Vx-770 drastically reduces CXCL8 (as well as CXCL1
      and CXCL2) transcripts and p38 MAPK phosphorylation in response to P. aeruginosa
      exposure through a CFTR-dependent mechanism. These results suggest that ORKAMBI
      has anti-inflammatory properties that could decrease lung inflammation and
      contribute to the observed beneficial impact of this treatment in CF patients.

PMID- 29351442
TI  - Measurements of pulmonary gas exchange efficiency using expired gas and oximetry:
      results in normal subjects.
AB  - We are developing a novel, noninvasive method for measuring the efficiency of
      pulmonary gas exchange in patients with lung disease. The patient wears an
      oximeter, and we measure the partial pressures of oxygen and carbon dioxide in
      inspired and expired gas using miniature analyzers. The arterial Po2 is then
      calculated from the oximeter reading and the oxygen dissociation curve, using the
      end-tidal Pco2 to allow for the Bohr effect. This calculation is only accurate
      when the oxygen saturation is <94%, and therefore, these normal subjects breathed
      12.5% oxygen. When the procedure is used in patients with hypoxemia, they breathe
      air. The Po2 difference between the end-tidal and arterial values is called the
      "oxygen deficit." Preliminary data show that this index increases substantially
      in patients with lung disease. Here we report measurements of the oxygen deficit
      in 20 young normal subjects (age 19 to 31 yr) and 11 older normal subjects (47 to
      88 yr). The mean value of the oxygen deficit in the young subjects was 2.02 +/-
      3.56 mmHg (means +/- SD). This mean is remarkably small. The corresponding value
      in the older group was 7.53 +/- 5.16 mmHg (means +/- SD). The results are
      consistent with the age-related trend of the traditional alveolar-arterial
      difference, which is calculated from the calculated ideal alveolar Po2 minus the
      measured arterial Po2. That measurement requires an arterial blood sample. The
      present study suggests that this noninvasive procedure will be valuable in
      assessing the degree of impaired gas exchange in patients with lung disease.

PMID- 29351443
TI  - Not simply the lesser of two evils.

PMID- 29351444
TI  - Activated human T lymphocytes inhibit TGFbeta-induced fibroblast to myofibroblast
      differentiation via prostaglandins D2 and E2.
AB  - In pulmonary fibrosis (PF), fibroblasts and myofibroblasts proliferate and
      deposit excessive extracellular matrix in the interstitium, impairing normal lung
      function. Because most forms of PF have a poor prognosis and limited treatment
      options, PF represents an urgent unmet need for novel, effective therapeutics.
      Although the role of immune cells in lung fibrosis is unclear, recent studies
      suggest that T lymphocyte (T cell) activation may be impaired in PF patients.
      Furthermore, we have previously shown that activated T cells can produce
      prostaglandins with anti-scarring potential. Here, we test the hypothesis that
      activated T cells directly inhibit myofibroblast differentiation using a
      coculture system. Coculture with activated primary blood-derived T cells, from
      both healthy human donors and PF patients, inhibited transforming growth factor
      beta-induced myofibroblast differentiation in primary human lung fibroblasts
      isolated from either normal or PF lung tissue. Coculture supernatants contained
      anti-fibrotic prostaglandins D2 and E2, and the inhibitory effect of coculture on
      myofibroblast differentiation was largely reversed when prostaglandin production
      was abrogated either by resting the T cells before coculture or via specific
      pharmacological inhibitors. Moreover, coculture conditions induced COX-2 in HLFs
      but not in T cells, suggesting that T cells deliver an activating signal to HLFs,
      which in turn produce anti-fibrotic prostaglandins. We show for the first time
      that coculture with activated primary human T lymphocytes strongly inhibits
      myofibroblast differentiation, revealing a novel cell-to-cell communication
      network with therapeutic implications for fibrotic lung diseases.

PMID- 29351445
TI  - Impact of HIV infection on alpha1-antitrypsin in the lung.
AB  - Emphysema is one of the most common lung diseases in HIV+ individuals. The
      pathogenesis of HIV-associated emphysema remains unclear; however, radiographic
      distribution and earlier age of presentation of emphysema in the lungs of HIV+
      patients are similar to deficiency of alpha1-antitrypsin (A1AT), a key elastase
      inhibitor in the lung. Reduced levels of circulating A1AT in HIV+ patients
      suggest a potential mechanism for emphysema development. In the present study we
      asked if A1AT levels and activity in the bronchoalveolar lavage fluid (BALF)
      differ in HIV+ and HIV- patients with and without emphysema. A1AT levels were
      measured by ELISA in plasma and BALF from a cohort of 21 HIV+ and 29 HIV-
      patients with or without emphysematous changes on chest CT scan. To analyze A1AT
      function, we measured elastase activity in the BALF and assessed oxidation and
      polymerization of A1AT by Western blotting. Total A1AT was increased in the BALF,
      but not in the plasma, of HIV+ compared with HIV- patients, regardless of the
      presence or absence of emphysema. However, antielastase activity was decreased in
      BALF from HIV+ patients, suggesting impaired A1AT function. Higher levels of the
      oxidized form of A1AT were detected in BALF from HIV+ than HIV- patients, which
      may account for the decreased antielastase activity. These findings suggest that,
      in the lungs of HIV+ patients, posttranslational modifications of A1AT produce a
      "functional deficiency" of this critical elastase inhibitor, which may contribute
      to emphysema development.

PMID- 29351447
TI  - Cigarette smoke dampens antiviral signaling in small airway epithelial cells by
      disrupting TLR3 cleavage.
AB  - Cigarette smokers and people exposed to second-hand smoke are at an increased
      risk for pulmonary viral infections, and yet the mechanism responsible for this
      heightened susceptibility is not understood. To understand the effect of
      cigarette smoke on susceptibility to viral infection, we used an air-liquid
      interface culture system and exposed primary human small airway epithelial cells
      (SAEC) to whole cigarette smoke, followed by treatment with the viral mimetic
      polyinosinic polycytidylic acid (poly I:C) or influenza A virus (IAV). We found
      that prior smoke exposure strongly inhibited production of proinflammatory
      (interleukin-6 and interleukin-8) and antiviral [interferon-gamma-induced protein
      10 (IP-10) and interferons] mediators in SAECs in response to poly I:C and IAV
      infection. Impaired antiviral responses corresponded to increased infection with
      IAV. This was associated with a decrease in phosphorylation of the key antiviral
      transcription factor interferon response factor 3 (IRF3). Here, we found that
      cigarette smoke exposure inhibited activation of Toll-like receptor 3 (TLR3) by
      impairing TLR3 cleavage, which was required for downstream phosphorylation of
      IRF3 and production of IP-10. These results identify a novel mechanism by which
      cigarette smoke exposure impairs antiviral responses in lung epithelial cells,
      which may contribute to increased susceptibility to respiratory infections.

PMID- 29351448
TI  - Extracellular oxidation in cystic fibrosis airway epithelium causes enhanced
      EGFR/ADAM17 activity.
AB  - The EGF receptor (EGFR)/a disintegrin and metalloproteinase 17 (ADAM17) signaling
      pathway mediates the shedding of growth factors and secretion of cytokines and is
      involved in chronic inflammation and tissue remodeling. Since these are hallmarks
      of cystic fibrosis (CF) lung disease, we hypothesized that CF transmembrane
      conductance regulator (CFTR) deficiency enhances EGFR/ADAM17 activity in human
      bronchial epithelial cells. In CF bronchial epithelial CFBE41o- cells lacking
      functional CFTR (iCFTR-) cultured at air-liquid interface (ALI) we found enhanced
      ADAM17-mediated shedding of the EGFR ligand amphiregulin (AREG) compared with
      genetically identical cells with induced CFTR expression (iCFTR+). Expression of
      the inactive G551D-CFTR did not have this effect, suggesting that active CFTR
      reduces EGFR/ADAM17 activity. This was confirmed in CF compared with normal
      differentiated primary human bronchial epithelial cells (HBEC-ALI). ADAM17
      mediated AREG shedding was tightly regulated by the EGFR/MAPK pathway. Compared
      with iCFTR+ cells, iCFTR- cells displayed enhanced apical presentation and
      phosphorylation of EGFR, in accordance with enhanced EGFR/ADAM17 activity in CFTR
      deficient cells. The nonpermeant natural antioxidant glutathione (GSH) strongly
      inhibited AREG release in iCFTR and in primary HBEC-ALI, suggesting that ADAM17
      activity is directly controlled by extracellular redox potentials in
      differentiated airway epithelium. Furthermore, the fluorescent redox probe
      glutaredoxin 1-redox-sensitive green fluorescent protein
      glycosylphosphatidylinositol (Grx1-roGFP-GPI) indicated more oxidized conditions
      in the extracellular space of iCFTR- cells, consistent with the role of CFTR in
      GSH transport. Our data suggest that in CFTR-deficient airway epithelial cells a
      more oxidized state of the extracellular membrane, likely caused by defective GSH
      secretion, leads to enhanced activity of the EGFR/ADAM17 signaling axis. In CF
      lungs this could contribute to tissue remodeling and hyperinflammation.

PMID- 29351446
TI  - Mechanisms and consequences of oxidative stress in lung disease: therapeutic
      implications for an aging populace.
AB  - The rapid expansion of the elderly population has led to the recent epidemic of
      age-related diseases, including increased incidence and mortality of chronic and
      acute lung diseases. Numerous studies have implicated aging and oxidative stress
      in the pathogenesis of various pulmonary diseases; however, despite recent
      advances in these fields, the specific contributions of aging and oxidative
      stress remain elusive. This review will discuss the consequences of aging on lung
      morphology and physiology, and how redox imbalance with aging contributes to lung
      disease susceptibility. Here, we focus on three lung diseases for which aging is
      a significant risk factor: acute respiratory distress syndrome (ARDS), chronic
      obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF).
      Preclinical and clinical development for redox- and senescence-altering
      therapeutic strategies are discussed, as well as scientific advancements that may
      direct current and future therapeutic development. A deeper understanding of how
      aging impacts normal lung function, redox balance, and injury-repair processes
      will inspire the development of new therapies to prevent and/or reverse age
      associated pulmonary diseases, and ultimately increase health span and longevity.
      This review is intended to encourage basic, clinical, and translational research
      that will bridge knowledge gaps at the intersection of aging, oxidative stress,
      and lung disease to fuel the development of more effective therapeutic strategies
      for lung diseases that disproportionately afflict the elderly.

PMID- 29351449
TI  - Personalized medicine in CF: from modulator development to therapy for cystic
      fibrosis patients with rare CFTR mutations.
AB  - Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting
      ~1 in 3,500 of the Caucasian population. CF is caused by mutations in the CF
      transmembrane conductance regulator (CFTR) gene. To date, more than 2,000 CFTR
      mutations have been identified, which produce a wide range of phenotypes. The
      CFTR protein, a chloride channel, is normally expressed on epithelial cells
      lining the lung, gut, and exocrine glands. Mutations in CFTR have led to
      pleiotropic effects in CF patients and have resulted in early morbidity and
      mortality. Research has focused on identifying small molecules, or modulators,
      that can restore CFTR function. In recent years, two modulators, ivacaftor
      (Kalydeco) and lumacaftor/ivacaftor (Orkambi), have been approved by the U.S.
      Food and Drug Administration to treat CF patients with certain CFTR mutations.
      The development of these modulators has served as proof-of-concept that targeting
      CFTR by modulators is a viable therapeutic option. Efforts to discover new
      modulators that could deliver a wider and greater clinical benefit are still
      ongoing. However, traditional randomized controlled trials (RCTs) require large
      numbers of patients and become impracticable to test the modulators' efficacy in
      CF patients with CFTR mutations at frequencies much lower than 1%, suggesting the
      need for personalized medicine in these CF patients.

PMID- 29351450
TI  - Cardiac vanilloid receptor-1 afferent depletion enhances stellate ganglion
      neuronal activity and efferent sympathetic response to cardiac stress.
AB  - Afferent fibers expressing the vanilloid receptor 1 (VR1) channel have been
      implicated in cardiac nociception; however, their role in modulating reflex
      responses to cardiac stress is not well understood. We evaluated this role in
      Yorkshire pigs by percutaneous epicardial application of resiniferatoxin (RTX), a
      toxic activator of the VR1 channel, resulting in the depletion of cardiac VR1
      expressing afferents. Hemodynamics, epicardial activation recovery intervals, and
      in vivo activity of stellate ganglion neurons (SGNs) were recorded in control and
      RTX-treated animals. Stressors included inferior vena cava or aortic occlusion
      and rapid right ventricular pacing (RVP) to induce dyssynchrony and ischemia. In
      the epicardium, stellate ganglia, and dorsal root ganglia, immunostaining for the
      VR1 channel, calcitonin gene-related peptide, and substance P was significantly
      diminished by RTX. RTX-treated animals exhibited higher basal systolic blood
      pressures and contractility than control animals. Reflex responses to epicardial
      bradykinin and capsaicin were mitigated by RTX. Cardiovascular reflex function,
      as assessed by inferior vena cava or aortic occlusion, was similar in RTX-treated
      versus control animals. RTX-treated animals exhibited resistance to hemodynamic
      collapse induced by RVP. Activation recovery interval shortening during RVP, a
      marker of cardiac sympathetic outflow, was greater in RTX-treated animals and
      exhibited significant delay in returning to baseline values after cessation of
      RVP. The basal firing rate of SGNs and firing rates in response to RVP were also
      greater in RTX-treated animals, as was the SGN network activity in response to
      cardiac stressors. These data suggest that elimination of cardiac nociceptive
      afferents reorganizes the central-peripheral nervous system interaction to
      enhance cardiac sympathetic outflow. NEW & NOTEWORTHY Our work demonstrates a
      role for cardiac vanilloid receptor-1-expressing afferents in reflex processing
      of cardiovascular stress. Current understanding suggests that elimination of
      vanilloid receptor-1 afferents would decrease reflex cardiac sympathetic outflow.
      We found, paradoxically, that sympathetic outflow to the heart is instead
      enhanced at baseline and during cardiac stress.

PMID- 29351452
TI  - Role of intracellular angiotensin II.
AB  - It has become clear that the vasoactive peptide angiotensin II, like other so
      called intracrines, can act in the intracellular space. Evidence has accumulated
      indicating that such angiotensin II activity can be upregulated in disease states
      and cause pathology. Indeed, other intracrines appear to be involved in disease
      pathogenesis as well. At the same time, nitric oxide, potentially a cell
      protective factor, has been shown to be upregulated by intracellular angiotensin
      II. Recently data have been developed indicating that other potentially
      protective factors are directly upregulated at neuronal nuclei by angiotensin II.
      This led to the suggestion that intracellular angiotensin II is cell protective
      and not pathological. Here, the data on both sides of this issue and a possible
      resolution are discussed. In summary, there is evidence for both protective and
      pathological actions of intracellular angiotensin, just as there is abundant
      evidence derived from whole animal physiology to indicate that angiotensin-driven
      signaling cascades, including angiotensin II type 2 receptor- and Mas receptor
      mediated events, can mitigate the effects of the angiotensin II/angiotensin II
      type 1 receptor axis (25). This mitigation does not negate the physiological and
      pathological importance of angiotensin II/angiotensin II type 1 receptor action
      but does expand our understanding of the workings of both intracellular and
      extracellular angiotensin II.

PMID- 29351453
TI  - Superoxide inhibition restores endothelium-dependent dilatation in aging arteries
      by enhancing impaired adherens junctions.
AB  - Endothelium-dependent, nitric oxide-mediated dilatation is impaired in aging
      arteries. The dysfunction reflects increased production of reactive oxygen
      species (ROS), is reversed by inhibiting superoxide with superoxide dismutase
      (SOD) mimics, and is assumed to reflect superoxide-mediated inactivation of
      nitric oxide. However, the dysfunction also reflects Src-dependent degradation
      and loss of vascular-endothelial (VE)-cadherin from adherens junctions, resulting
      in a selective impairment in the ability of the junctions to amplify endothelial
      dilatation. Experiments therefore tested the hypothesis that SOD mimics might
      restore endothelial dilation in aging arteries by inhibiting Src and protecting
      endothelial adherens junctions. Tail arteries from young and aging Fisher 344
      rats were processed for functional (pressure myograph), biochemical (immunoblot),
      and morphological (immunofluorescence) analyses. Cell-permeable SOD mimics
      [manganese(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) or tempol] did
      not affect acetylcholine-induced dilatation in young arteries but increased
      responses and restored normal dilator function in aging arteries. In aging
      arteries, MnTMPyP decreased Src activity (immunoblots of Tyr416 phosphorylated
      compared with total Src), increased the intensity and width of VE-cadherin
      staining at endothelial junctions, and increased VE-cadherin levels in Triton X
      100-insoluble lysates, which represents the junctional protein. Because of aging
      induced junctional disruption, inhibiting VE-cadherin clustering at adherens
      junctions with a function-blocking antibody does not affect acetylcholine-induced
      dilatation in aging arteries. However, the antibody prevented SOD mimics from
      restoring acetylcholine-induced dilatation in aging arteries. Therefore, SOD
      mimics improve impaired adherens junctions in aging endothelium, which is
      essential for SOD mimics to restore endothelium-dependent dilatation in aging
      arteries. The results suggest an important new pathological role for ROS in aging
      endothelium, namely, disruption of adherens junctions. NEW & NOTEWORTHY Aging
      induced endothelial dysfunction is reversed by SOD mimics. This study
      demonstrates that they improve impaired adherens junctions in aging endothelium
      and that their restoration of endothelial dilatation is dependent on increased
      junctional activity. The results suggest a novel role for oxygen radicals in
      vascular aging, namely, disruption of adherens junctions.

PMID- 29351454
TI  - Detrimental effects of 2-arachidonoylglycerol on whole blood platelet aggregation
      and on cerebral blood flow after a focal ischemic insult in rats.
AB  - 2-Arachidonoylglycerol (2-AG) is a major modulator of blood flow and platelet
      aggregation and a potential neuroprotectant. The present study investigated, for
      the first time, the effects of 2-AG on cerebral blood flow (CBF) in the first
      critical hours during middle cerebral artery occlusion (MCAO) and on platelet
      aggregation in rats. Adult male Sprague-Dawley rats ( n = 30) underwent permanent
      MCAO under isoflurane anesthesia and were randomly assigned to receive either 2
      AG (6 mg/kg iv), monoacylglycerol lipase inhibitor JZL-184 (10 mg/kg iv), or
      vehicle ( n = 6 rats/group) treatment. CBF and cardiovascular responses were
      measured, by a blinded investigator, for up to 4 h. In separate experiments,
      platelet aggregation by 2-AG (19-300 uM) was assessed by whole blood aggregometry
      ( n = 40). 2-AG and JZL-184 significantly increased the severity of the CBF
      deficit versus vehicle (20.2 +/- 8.8% and 22.7 +/- 6.4% vs. 56.4 +/- 12.1% of pre
      MCAO baseline, respectively, P < 0.05) but had no effect on blood pressure or
      heart rate. While JZL-184 significantly increased the number of thrombi after
      MCAO, this did not reach significance by 2-AG. 2-AG induced platelet aggregation
      in rat whole blood in a similar manner to arachidonic acid and was significantly
      reduced by the cyclooxygenase inhibitors indomethacin and flurbiprofen and the
      thromboxane receptor antagonist ICI 192,605 ( P < 0.05). This is the first study
      showing that 2-AG increases the severity of the CBF deficit during MCAO, and
      further interrogation confirmed 2-AG-induced platelet aggregation in rats. These
      findings are important because 2-AG had previously been shown to exert
      neuroprotective actions and therefore force us to reevaluate the circumstances
      under which 2-AG is beneficial. NEW & NOTEWORTHY 2-Arachidonoylglycerol (2-AG)
      has neuroprotective properties; however, the present study revealed that 2-AG
      increases the severity of the cerebral blood flow deficit during middle cerebral
      artery occlusion in rats. Further interrogation showed that 2-AG induces platelet
      aggregation in rats. These findings force us to reevaluate the circumstances
      under which 2-AG is beneficial.

PMID- 29351455
TI  - Thrombosis and systemic and cardiac oxidative stress and DNA damage induced by
      pulmonary exposure to diesel exhaust particles and the effect of nootkatone
      thereon.
AB  - Adverse cardiovascular effects of particulate air pollution persist even at lower
      concentrations than those of the current air quality limit. Therefore,
      identification of safe and effective measures against particle-induced
      cardiovascular toxicity is needed. Nootkatone is a sesquiterpenoid in grapefruit
      with diverse bioactivities including anti-inflammatory and antioxidant effects.
      However, its protective effect on the cardiovascular injury induced by diesel
      exhaust particles (DEPs) has not been studied before. We assessed the possible
      protective effect of nootkatone (90 mg/kg) administered by gavage 1 h before
      intratracheal instillation of DEPs (30 MUg/mouse). Twenty-four hours after the
      intratracheal administration of DEPs, various thrombotic and cardiac parameters
      were assessed. Nootkatone inhibited the prothrombotic effect induced by DEPs in
      pial arterioles and venules in vivo and platelet aggregation in whole blood in
      vitro. Also, nootkatone prevented the shortening of activated partial
      thromboplastin time and prothrombin time induced by DEPs. Nootkatone inhibited
      the increase of plasma concentration of fibrinogen, plasminogen activator
      inhibitor-1, interleukin-6, and lipid peroxidation induced by DEPs.
      Immunohistochemically, hearts showed an analogous increase in glutathione and
      nuclear factor erythroid-derived 2-like 2 expression by cardiac myocytes and
      endothelial cells after DEP exposure, and these effects were enhanced in mice
      treated with nootkatone + DEPs. Likewise, heme oxygenase-1 was increased in mice
      treated with nootkatone + DEPs compared with those treated with DEPs or
      nootkatone + saline. The DNA damage caused by DEPs was prevented by nootkatoone
      pretreatment. In conclusion, nootkatoone alleviates DEP-induced thrombogenicity
      and systemic and cardiac oxidative stress and DNA damage, at least partly,
      through nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1
      activation. NEW & NOTEWORTHY Nootkatoone, a sesquiterpenoid found in grapefruit,
      alleviates the thrombogenicity and systemic and cardiac oxidative stress and DNA
      damage in mice exposed to diesel exhaust particles. Nootkatone-induced boosting
      of nuclear factor erythroid-derived 2-like 2 and heme oxygenase-1 levels in the
      heart of mice exposed to diesel exhaust particles suggests that its protective
      effect is, at least partly, mediated through nuclear factor erythroid-derived 2
      like 2 and heme oxygenase-1 activation.

PMID- 29351457
TI  - Important role of endothelium-dependent hyperpolarization in the pulmonary
      microcirculation in male mice: implications for hypoxia-induced pulmonary
      hypertension.
AB  - Endothelium-dependent hyperpolarization (EDH) plays important roles in the
      systemic circulation, whereas its role in the pulmonary circulation remains
      largely unknown. Furthermore, the underlying mechanisms of pulmonary hypertension
      (PH) also remain to be elucidated. We thus aimed to elucidate the role of EDH in
      pulmonary circulation in general and in PH in particular. In isolated perfused
      lung and using male wild-type mice, endothelium-dependent relaxation to
      bradykinin (BK) was significantly reduced in the presence of Nomega-nitro-l
      arginine by ~50% compared with those in the presence of indomethacin, and the
      combination of apamin plus charybdotoxin abolished the residual relaxation,
      showing the comparable contributions of nitric oxide (NO) and EDH in the
      pulmonary microcirculation under physiological conditions. Catalase markedly
      inhibited EDH-mediated relaxation, indicating the predominant contribution of
      endothelium-derived H2O2. BK-mediated relaxation was significantly reduced at day
      1 of hypoxia, whereas it thereafter remained unchanged until day 28. EDH-mediated
      relaxation was diminished at day 2 of hypoxia, indicating a transition from EDH
      to NO in BK-mediated relaxation before the development of hypoxia-induced PH.
      Mechanistically, chronic hypoxia enhanced endothelial NO synthase expression and
      activity associated with downregulation of caveolin-1. Nitrotyrosine levels were
      significantly higher in vascular smooth muscle of pulmonary microvessels under
      chronic hypoxia than under normoxia. A similar transition of the mediators in BK
      mediated relaxation was also noted in the Sugen hypoxia mouse model. These
      results indicate that EDH plays important roles in the pulmonary microcirculation
      in addition to NO under normoxic conditions and that impaired EDH-mediated
      relaxation and subsequent nitrosative stress may be potential triggers of the
      onset of PH. NEW & NOTEWORTHY This study provides novel evidence that both
      endothelium-dependent hyperpolarization and nitric oxide play important roles in
      endothelium-dependent relaxation in the pulmonary microcirculation under
      physiological conditions in mice and that hypoxia first impairs endothelium
      dependent hyperpolarization-mediated relaxation, with compensatory upregulation
      of nitric oxide, before the development of hypoxia-induced pulmonary
      hypertension.

PMID- 29351451
TI  - Guidelines for experimental models of myocardial ischemia and infarction.
AB  - Myocardial infarction is a prevalent major cardiovascular event that arises from
      myocardial ischemia with or without reperfusion, and basic and translational
      research is needed to better understand its underlying mechanisms and
      consequences for cardiac structure and function. Ischemia underlies a broad range
      of clinical scenarios ranging from angina to hibernation to permanent occlusion,
      and while reperfusion is mandatory for salvage from ischemic injury, reperfusion
      also inflicts injury on its own. In this consensus statement, we present
      recommendations for animal models of myocardial ischemia and infarction. With
      increasing awareness of the need for rigor and reproducibility in designing and
      performing scientific research to ensure validation of results, the goal of this
      review is to provide best practice information regarding myocardial ischemia
      reperfusion and infarction models. Listen to this article's corresponding podcast
      at ajpheart.podbean.com/e/guidelines-for-experimental-models-of-myocardial
      ischemia-and-infarction/.

PMID- 29351458
TI  - Differences in L-type Ca2+ channel activity partially underlie the regional
      dichotomy in pumping behavior by murine peripheral and visceral lymphatic
      vessels.
AB  - We identified a regional dichotomy in murine lymphatic contractile function with
      regard to vessel location within the periphery or visceral cavity. All vessels
      isolated from peripheral regions [cervical, popliteal, inguinal, axillary, and
      internodal inguinal axillary (Ing-Ax)] developed robust contractions with maximal
      ejection fractions (EFs) of 50-80% in our ex vivo isobaric myograph experiments.
      Conversely, vessels isolated from the visceral cavity (mesenteric, thoracic duct,
      and iliac) demonstrated maximal EFs of <=10%. Using pressure myography, sharp
      electrode membrane potential recordings, and Ca2+ imaging, we assessed the role
      of L-type Ca2+ channels in this contractile dichotomy. Ing-Ax membrane potential
      revealed a ~2-s action potential (AP) cycle (resting -35 mV, spike -5 mV, and
      plateau -11 mV) with a plateau phase that was significantly lengthened by the L
      type Ca2+ channel agonist Bay K8644 (BayK; 100 nM). APs recorded from mesenteric
      vessels, however, displayed a slower upstroke and an elongated time over
      threshold. BayK (100 nM) increased the mesenteric AP upstroke velocity and
      plateau duration but also significantly hyperpolarized the vessel. Contractions
      of vessels from both regions were preceded by Ca2+ flashes, detected with a
      smooth muscle-specific endogenous Ca2+ reporter, that typically were coordinated
      over the length of the vessel. Similar to the membrane potential recordings, Ca2+
      flashes in mesenteric vessels were weaker and had a slower rise time but were
      longer lasting than those in Ing-Ax vessels. BayK (100 nM) significantly
      increased the Ca2+ transient amplitude and duration in both vessels and decreased
      time to peak Ca2+ in mesenteric vessels. However, a higher concentration (1 MUM)
      of BayK was required to produce even a modest increase in EF in visceral
      lymphatics, which remained at <20%. NEW & NOTEWORTHY Lymphatic collecting vessels
      isolated from murine peripheral tissues, but not from the visceral cavities,
      display robust contractile behavior similar to lymphatic vessels from other
      animal models and humans. These differences are partially explained by L-type
      Ca2+ channel activity as revealed by the first measurements of murine lymphatic
      action potentials and contraction-associated Ca2+ transients.

PMID- 29351460
TI  - Macrophage-dependent impairment of alpha2-adrenergic autoreceptor inhibition of
      Ca2+ channels in sympathetic neurons from DOCA-salt but not high-fat diet-induced
      hypertensive rats.
AB  - DOCA-salt and obesity-related hypertension are associated with inflammation and
      sympathetic nervous system hyperactivity. Prejunctional alpha2-adrenergic
      receptors (alpha2ARs) provide negative feedback to norepinephrine release from
      sympathetic nerves through inhibition of N-type Ca2+ channels. Increased neuronal
      norepinephrine release in DOCA-salt and obesity-related hypertension occurs
      through impaired alpha2AR signaling; however, the mechanisms involved are
      unclear. Mesenteric arteries are resistance arteries that receive sympathetic
      innervation from the superior mesenteric and celiac ganglia (SMCG). We tested the
      hypothesis that macrophages impair alpha2AR-mediated inhibition of Ca2+ channels
      in SMCG neurons from DOCA-salt and high-fat diet (HFD)-induced hypertensive rats.
      Whole cell patch-clamp methods were used to record Ca2+ currents from SMCG
      neurons maintained in primary culture. We found that DOCA-salt, but not HFD
      induced, hypertension caused macrophage accumulation in mesenteric arteries,
      increased SMCG mRNA levels of monocyte chemoattractant protein-1 and tumor
      necrosis factor-alpha, and impaired alpha2AR-mediated inhibition of Ca2+ currents
      in SMCG neurons. alpha2AR dysfunction did not involve changes in alpha2AR
      expression, desensitization, or downstream signaling factors. Oxidative stress
      impaired alpha2AR-mediated inhibition of Ca2+ currents in SMCG neurons and
      resulted in receptor internalization in human embryonic kidney-293T cells.
      Systemic clodronate-induced macrophage depletion preserved alpha2AR function and
      lowered blood pressure in DOCA-salt rats. HFD caused hypertension without obesity
      in Sprague-Dawley rats and hypertension with obesity in Dahl salt-sensitive rats.
      HFD-induced hypertension was not associated with inflammation in SMCG and
      mesenteric arteries or alpha2AR dysfunction in SMCG neurons. These results
      suggest that macrophage-mediated alpha2AR dysfunction in the mesenteric
      circulation may only be relevant to mineralocorticoid-salt excess. NEW &
      NOTEWORTHY Here, we identify a contribution of macrophages to hypertension
      development through impaired alpha2-adrenergic receptor (alpha2AR)-mediated
      inhibition of sympathetic nerve terminal Ca2+ channels in DOCA-salt hypertensive
      rats. Impaired alpha2AR function may involve oxidative stress-induced receptor
      internalization. alpha2AR dysfunction may be unique to mineralocorticoid-salt
      excess, as it does not occur in obesity-related hypertension.

PMID- 29351456
TI  - Guidelines for measuring cardiac physiology in mice.
AB  - Cardiovascular disease is a leading cause of death, and translational research is
      needed to understand better mechanisms whereby the left ventricle responds to
      injury. Mouse models of heart disease have provided valuable insights into
      mechanisms that occur during cardiac aging and in response to a variety of
      pathologies. The assessment of cardiovascular physiological responses to injury
      or insult is an important and necessary component of this research. With
      increasing consideration for rigor and reproducibility, the goal of this
      guidelines review is to provide best-practice information regarding how to
      measure accurately cardiac physiology in animal models. In this article, we
      define guidelines for the measurement of cardiac physiology in mice, as the most
      commonly used animal model in cardiovascular research. Listen to this article's
      corresponding podcast at http://ajpheart.podbean.com/e/guidelines-for-measuring
      cardiac-physiology-in-mice/ .

PMID- 29351459
TI  - Guidelines for authors and reviewers on antibody use in physiology studies.
AB  - Antibody use is a critical component of cardiovascular physiology research, and
      antibodies are used to monitor protein abundance (immunoblot analysis) and
      protein expression and localization (in tissue by immunohistochemistry and in
      cells by immunocytochemistry). With ongoing discussions on how to improve
      reproducibility and rigor, the goal of this review is to provide best practice
      guidelines regarding how to optimize antibody use for increased rigor and
      reproducibility in both immunoblot analysis and immunohistochemistry approaches.
      Listen to this article's corresponding podcast at
      http://ajpheart.podbean.com/e/guidelines-on-antibody-use-in-physiology-studies/ .

PMID- 29351461
TI  - Exercise training induces eNOS coupling and restores relaxation in coronary
      arteries of heart failure rats.
AB  - Exercise training (ET) has emerged as a nonpharmacological therapy for
      cardiovascular diseases because of its helpful milieu for improving vascular
      function. The aim of the present study was to assess whether ET reverses the
      alterations in vascular reactivity observed in heart failure (HF)-related
      coronary arteries and to elucidate the molecular mechanisms involved in these
      adjustments. Male Wistar rats were subjected to either coronary artery ligation
      or sham operation. Four weeks after the surgery, rats were divided into two
      groups: untrained HF (UHF) and exercise-trained HF (THF). ET was conducted on a
      treadmill for 8 wk. An untrained SO group was included in the study as a normal
      control. ET restored the impaired acetylcholine (ACh)- and sodium nitroprusside
      induced relaxation in coronary arteries to levels of the control. Oxidative
      stress and reduced nitric oxide (NO) production were observed in UHF, whereas ET
      restored both parameters to the levels of the control. Expression levels of
      endothelial NO synthase (eNOS) and soluble guanylyl cyclase subunits were
      increased in coronary arteries of UHF rats but reduced in THF rats.
      Tetrahydrobiopterin restored ACh-induced NO production in the UHF group,
      indicating that eNOS was uncoupled. ET increased the eNOS dimer-to-monomer ratio
      and expression of GTP cyclohydrolase 1, thus increasing NO bioavailability. Taken
      together, these findings demonstrate that ET reverses the dysfunction of the
      NO/soluble guanylyl cyclase pathway present in coronary arteries of HF rats.
      These effects of ET are associated with increased GTP cyclohydrolase 1
      expression, restoration of NO bioavailability, and reduced oxidative stress
      through eNOS coupling. NEW & NOTEWORTHY The present study provides a molecular
      basis for the exercise-induced improvement in coronary arteries function in heart
      failure. Increasing the expression of GTP cyclohydrolase 1, the rate-limiting
      enzyme in the de novo biosynthesis of tetrahydrobiopterin, exercise training
      couples endothelial nitric oxide synthase, reduces oxidative stress, and
      increases nitric oxide bioavailability and sensitivity in coronary arteries of
      heart failure rats.

PMID- 29351462
TI  - Maximal strength training-induced improvements in forearm work efficiency are
      associated with reduced blood flow.
AB  - Maximal strength training (MST) improves work efficiency. However, since blood
      flow is greatly dictated by muscle contractions in arms during exercise and
      vascular conductance is lower, it has been indicated that arms rely more upon
      adapting oxygen extraction than legs in response to the enhanced work efficiency.
      Thus, to investigate if metabolic and vascular responses are arm specific, we
      used Doppler-ultrasound and a catheter placed in the subclavian vein to measure
      blood flow and the arteriovenous oxygen difference during steady-state work in
      seven young men [24 +/- 3 (SD) yr] following 6 wk of handgrip MST. As expected,
      MST improved maximal strength (49 +/- 9 to 62 +/- 10 kg) and the rate of force
      development (923 +/- 224 to 1,086 +/- 238 N/s), resulting in a reduced submaximal
      oxygen uptake (30 +/- 9 to 24 +/- 10 ml/min) and concomitantly increased work
      efficiency (9.3 +/- 2.5 to 12.4 +/- 3.9%) (all P < 0.05). In turn, the work
      efficiency improvement was associated with reduced blood flow (486 +/- 102 to 395
      +/- 114 ml/min), mediated by a lower blood velocity (43 +/- 8 to 32 +/- 6 cm/s)
      (all P < 0.05). Conduit artery diameter and the arteriovenous oxygen difference
      remained unaltered. The maximal work test revealed an increased time to
      exhaustion (949 +/- 239 to 1,102 +/- 292 s) and maximal work rate (both P < 0.05)
      but no change in peak oxygen uptake. In conclusion, despite prior indications of
      metabolic and vascular limb-specific differences, these results reveal that
      improved work efficiency after small muscle mass strength training in the upper
      extremities is accompanied by a blood flow reduction and coheres with what has
      been documented for lower extremities. NEW & NOTEWORTHY Maximal strength training
      increases skeletal muscle work efficiency. Oxygen extraction has been indicated
      to be the adapting component with this increased work efficiency in arms.
      However, we document that decreased blood flow, achieved by blood velocity
      reduction, is the adapting mechanism responding to the improved aerobic
      metabolism in the forearm musculature.

PMID- 29351463
TI  - Intermediary metabolism and fatty acid oxidation: novel targets of electron
      transport chain-driven injury during ischemia and reperfusion.
AB  - Cardiac ischemia-reperfusion (I/R) damages the electron transport chain (ETC),
      causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at
      complex I during ischemia protects the ETC and decreases cardiac injury. In the
      present study, we used an unbiased proteomic approach to analyze the extent of
      ETC-driven mitochondrial injury during I/R. Isolated-perfused mouse (C57BL/6)
      hearts underwent 25-min global ischemia (37 degrees C) and 30-min reperfusion. In
      treated hearts, amobarbital (2 mM) was given for 1 min before ischemia to rapidly
      and reversibly block the ETC at complex I. Mitochondria were isolated at the end
      of reperfusion and subjected to unbiased proteomic analysis using tryptic
      digestion followed by liquid chromatography-mass spectrometry with isotope tags
      for relative and absolute quantification. Amobarbital treatment decreased cardiac
      injury and protected respiration. I/R decreased the content ( P < 0.05) of
      multiple mitochondrial matrix enzymes involved in intermediary metabolism
      compared with the time control. The contents of several enzymes in fatty acid
      oxidation were decreased compared with the time control. Blockade of ETC during
      ischemia largely prevented the decreases. Thus, after I/R, not only the ETC but
      also multiple pathways of intermediary metabolism sustain damage initiated by the
      ETC. If these damaged mitochondria persist in the myocyte, they remain a potent
      stimulus for ongoing injury and the transition to cardiomyopathy during prolonged
      reperfusion. Modulation of ETC function during early reperfusion is a key
      strategy to preserve mitochondrial metabolism and to decrease persistent
      mitochondria-driven injury during longer periods of reperfusion that predispose
      to ventricular dysfunction and heart failure. NEW & NOTEWORTHY Ischemia
      reperfusion (I/R) damages mitochondria, which could be protected by reversible
      blockade of the electron transport chain (ETC). Unbiased proteomics with isotope
      tags for relative and absolute quantification analyzed mitochondrial damage
      during I/R and found that multiple enzymes in the tricarboxylic acid cycle, fatty
      acid oxidation, and ETC decreased, which could be prevented by ETC blockade.
      Strategic ETC modulation can reduce mitochondrial damage and cardiac injury.

PMID- 29351465
TI  - Emerging potential benefits of modulating NAD+ metabolism in cardiovascular
      disease.
AB  - Nicotinamide adenine dinucleotide (NAD+) and related metabolites are central
      mediators of fuel oxidation and bioenergetics within cardiomyocytes.
      Additionally, NAD+ is required for the activity of multifunctional enzymes,
      including sirtuins and poly(ADP-ribose) polymerases that regulate
      posttranslational modifications, DNA damage responses, and Ca2+ signaling. Recent
      research has indicated that NAD+ participates in a multitude of processes
      dysregulated in cardiovascular diseases. Therefore, supplementation of NAD+
      precursors, including nicotinamide riboside that boosts or repletes the NAD+
      metabolome, may be cardioprotective. This review examines the molecular
      physiology and preclinical data with respect to NAD+ precursors in heart failure
      related cardiac remodeling, ischemic-reperfusion injury, and arrhythmias. In
      addition, alternative NAD+-boosting strategies and potential systemic effects of
      NAD+ supplementation with implications on cardiovascular health and disease are
      surveyed.

PMID- 29351466
TI  - Telomerase reverse transcriptase protects against angiotensin II-induced
      microvascular endothelial dysfunction.
AB  - A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease
      by reducing nitric oxide (NO) levels, leading to loss of NO's vasodilator and
      anti-inflammatory effects. Although primarily studied in larger conduit arteries,
      excess ROS release and a corresponding loss of NO also occur in smaller
      resistance arteries of the microcirculation, but the underlying mechanisms and
      therapeutic targets have not been fully characterized. We examined whether either
      of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or
      telomerase RNA component (TERC), affect microvascular ROS production and peak
      vasodilation at baseline and in response to in vivo administration to angiotensin
      II (ANG II). We report that genetic loss of TERT [maximal dilation: 52.0 +/- 6.1%
      with vehicle, 60.4 +/- 12.9% with Nomega-nitro-l-arginine methyl ester (l-NAME),
      and 32.2 +/- 12.2% with polyethylene glycol-catalase (PEG-Cat) ( P < 0.05), means
      +/- SD, n = 9-19] but not TERC [maximal dilation: 79 +/- 5% with vehicle, 10.7 +/
      9.8% with l-NAME ( P < 0.05), and 86.4 +/- 8.4% with PEG-Cat, n = 4-7] promotes
      flow-induced ROS formation. Moreover, TERT knockout exacerbates the microvascular
      dysfunction resulting from in vivo ANG II treatment, whereas TERT overexpression
      is protective [maximal dilation: 88.22 +/- 4.6% with vehicle vs. 74.0 +/- 7.3%
      with ANG II (1,000 ng.kg-1.min-1) ( P = not significant), n = 4]. Therefore, loss
      of TERT but not TERC may be a key contributor to the elevated microvascular ROS
      levels and reduced peak dilation observed in several cardiovascular disease
      pathologies. NEW & NOTEWORTHY This study identifies telomerase reverse
      transcriptase (TERT) but not telomerase RNA component as a key factor regulating
      endothelium-dependent dilation in the microcirculation. Loss of TERT activity
      leads to microvascular dysfunction but not conduit vessel dysfunction in first
      generation mice. In contrast, TERT is protective in the microcirculation in the
      presence of prolonged vascular stress. Understanding the mechanism of how TERT
      protects against vascular stress represents a novel target for the treatment of
      vascular disorders.

PMID- 29351468
TI  - GABAergic contribution to the muscle mechanoreflex-mediated heart rate responses
      at the onset of exercise in humans.
AB  - Previous studies have indicated that central GABAergic mechanisms are involved in
      the heart rate (HR) responses at the onset of exercise. On the basis of previous
      research that showed similar increases in HR during passive and active cycling,
      we reasoned that the GABAergic mechanisms involved in the HR responses at the
      exercise onset are primarily mediated by muscle mechanoreceptor afferents.
      Therefore, in this study, we sought to determine whether central GABA mechanisms
      are involved in the muscle mechanoreflex-mediated HR responses at the onset of
      exercise in humans. Twenty-eight healthy subjects (14 men and 14 women) aged
      between 18 and 35 yr randomly performed three bouts of 5-s passive and active
      cycling under placebo and after oral administration of diazepam (10 mg), a
      benzodiazepine that produces an enhancement in GABAA activity. Beat-to-beat HR
      (electrocardiography) and arterial blood pressure (finger photopletysmography)
      were continuously measured. Electromyography of the vastus lateralis was obtained
      to confirm no electrical activity during passive trials. HR increased from rest
      under placebo and further increased after administration of diazepam in both
      passive (change: 12 +/- 1 vs. 17 +/- 1 beats/min, P < 0.01) and active (change:
      14 +/- 1 vs. 18 +/- 1 beats/min, P < 0.01) cycling. Arterial blood pressure
      increased from rest similarly during all conditions ( P > 0.05). Importantly, no
      sex-related differences were found in any variables during experiments. These
      findings demonstrate, for the first time, that the GABAergic mechanisms
      significantly contribute to the muscle mechanoreflex-mediated HR responses at the
      onset of exercise in humans. NEW & NOTEWORTHY We found that passive and voluntary
      cycling evokes similar increases in heart rate and that these responses were
      enhanced after diazepam administration, a benzodiazepine that enhances GABAA
      activity. These findings suggest that the GABAergic system may contribute to the
      muscle mechanoreflex-mediated vagal withdrawal at the onset of exercise in
      humans.

PMID- 29351464
TI  - Vitamin D and regulation of vascular cell function.
AB  - Vitamin D deficiency is linked to pathogenesis of many diseases including
      cardiovascular, cancer, and various eye diseases. In recent years, important
      roles for vitamin D in regulation of immune function, inflammation, angiogenesis,
      and aging have been demonstrated. Thus, vitamin D and its analogs have been
      evaluated for the treatment of various types of cancer and chronic diseases. We
      have previously shown that the active form of vitamin D [1,25(OH)2D3] is a potent
      inhibitor of angiogenesis. This activity is consistent with the important role
      proposed for vitamin D and its analogs in the mitigation of tumor growth through
      inhibition of angiogenesis. Here, we review the important nutritional value of
      vitamin D and the abnormalities linked to its deficiency. We will explore its
      potential role as a regulator of angiogenesis and vascular cell function and the
      role vitamin D receptor (VDR) expression plays in these activities during
      vascular development and neovascularization. Our studies have established an
      important role for 1,25(OH)2D3 and VDR in the regulation of perivascular
      supporting cell function. In addition, the interaction of 1,25(OH)2D3 and VDR is
      essential for these activities and inhibition of neovascularization. Delineating
      the signaling pathways involved and identification of genes that are the target
      of 1,25(OH)2D3 regulation in vascular cells will allow us to identify novel
      pathways that are targets for regulation of vascular function and angiogenesis.

PMID- 29351467
TI  - From ionic to cellular variability in human atrial myocytes: an integrative
      computational and experimental study.
AB  - Variability refers to differences in physiological function between individuals,
      which may translate into different disease susceptibility and treatment efficacy.
      Experiments in human cardiomyocytes face wide variability and restricted tissue
      access; under these conditions, computational models are a useful complementary
      tool. We conducted a computational and experimental investigation in
      cardiomyocytes isolated from samples of the right atrial appendage of patients
      undergoing cardiac surgery to evaluate the impact of variability in action
      potentials (APs) and subcellular ionic densities on Ca2+ transient dynamics.
      Results showed that 1) variability in APs and ionic densities is large, even
      within an apparently homogenous patient cohort, and translates into +/-100%
      variation in ionic conductances; 2) experimentally calibrated populations of
      models with wide variations in ionic densities yield APs overlapping with those
      obtained experimentally, even if AP characteristics of the original generic model
      differed significantly from experimental APs; 3) model calibration with AP
      recordings restricts the variability in ionic densities affecting upstroke and
      resting potential, but redundancy in repolarization currents admits substantial
      variability in ionic densities; and 4) model populations constrained with
      experimental APs and ionic densities exhibit three Ca2+ transient phenotypes,
      differing in intracellular Ca2+ handling and Na+/Ca2+ membrane extrusion. These
      findings advance our understanding of the impact of variability in human atrial
      electrophysiology. NEW & NOTEWORTHY Variability in human atrial electrophysiology
      is investigated by integrating for the first time cellular-level and ion channel
      recordings in computational electrophysiological models. Ion channel calibration
      restricts current densities but not cellular phenotypic variability. Reduced
      Na+/Ca2+ exchanger is identified as a primary mechanism underlying diastolic Ca2+
      fluctuations in human atrial myocytes.

PMID- 29351469
TI  - Inhibition of mTOR protects the blood-brain barrier in models of Alzheimer's
      disease and vascular cognitive impairment.
AB  - An intact blood-brain barrier (BBB) limits entry of proinflammatory and
      neurotoxic blood-derived factors into the brain parenchyma. The BBB is damaged in
      Alzheimer's disease (AD), which contributes significantly to the progression of
      AD pathologies and cognitive decline. However, the mechanisms underlying BBB
      breakdown in AD remain elusive, and no interventions are available for treatment
      or prevention. We and others recently established that inhibition of the
      mammalian/mechanistic target of rapamycin (mTOR) pathway with rapamycin yields
      significant neuroprotective effects, improving cerebrovascular and cognitive
      function in mouse models of AD. To test whether mTOR inhibition protects the BBB
      in neurological diseases of aging, we treated hAPP(J20) mice modeling AD and low
      density lipoprotein receptor-null (LDLR-/-) mice modeling vascular cognitive
      impairment with rapamycin. We found that inhibition of mTOR abrogates BBB
      breakdown in hAPP(J20) and LDLR-/- mice. Experiments using an in vitro BBB model
      indicated that mTOR attenuation preserves BBB integrity through upregulation of
      specific tight junction proteins and downregulation of matrix metalloproteinase-9
      activity. Together, our data establish mTOR activity as a critical mediator of
      BBB breakdown in AD and, potentially, vascular cognitive impairment and suggest
      that rapamycin and/or rapalogs could be used for the restoration of BBB
      integrity. NEW & NOTEWORTHY This report establishes mammalian/mechanistic target
      of rapamycin as a critical mediator of blood-brain barrier breakdown in models of
      Alzheimer's disease and vascular cognitive impairment and suggests that drugs
      targeting the target of rapamycin pathway could be used for the restoration of
      blood-brain barrier integrity in disease states.

PMID- 29351470
TI  - Increased (pro)renin receptor expression in the subfornical organ of hypertensive
      humans.
AB  - The central nervous system plays an important role in essential hypertension in
      humans and in animal models of hypertension through modulation of sympathetic
      activity and Na+ and body fluid homeostasis. Data from animal models of
      hypertension suggest that the renin-angiotensin system in the subfornical organ
      (SFO) of the brain is critical for hypertension development. We recently reported
      that the brain (pro)renin receptor (PRR) is a novel component of the brain renin
      angiotensin system and could be a key initiator of the pathogenesis of
      hypertension. Here, we examined the expression level and cellular distribution of
      PRR in the SFO of postmortem human brains to assess its association with the
      pathogenesis of human hypertension. Postmortem SFO tissues were collected from
      hypertensive and normotensive human subjects. Immunolabeling for the PRR and a
      retrospective analysis of clinical data were performed. We found that human PRR
      was prominently expressed in most neurons and microglia, but not in astrocytes,
      in the SFO. Importantly, PRR levels in the SFO were elevated in hypertensive
      subjects. Moreover, PRR immunoreactivity was significantly correlated with
      systolic blood pressure but not body weight, age, or diastolic blood pressure.
      Interestingly, this correlation was independent of antihypertensive drug therapy.
      Our data indicate that PRR in the SFO may be a key molecular player in the
      pathogenesis of human hypertension and, as such, could be an important focus of
      efforts to understand the neurogenic origin of hypertension. NEW & NOTEWORTHY
      This study provides evidence that, in the subfornical organ of the human brain,
      the (pro)renin receptor is expressed in neurons and microglia cells but not in
      astrocytes. More importantly, (pro)renin receptor immunoreactivity in the
      subfornical organ is increased in hypertensive humans and is significantly
      correlated with systolic blood pressure.

PMID- 29351471
TI  - When higher cholesterol is better: membrane cholesterol loss and endothelial Ca2+
      signaling.

PMID- 29351472
TI  - Role of lysyl oxidase on microvascular function.

PMID- 29351473
TI  - Sympathetically mediated cardiac responses to isolated muscle metaboreflex
      activation following exercise are modulated by body position in humans.
AB  - Isolated muscle metaboreflex activation with posthandgrip exercise ischemia (PEI)
      increases sympathetic nerve activity and partially maintains the exercise-induced
      increase in blood pressure, but a smaller heart rate (HR) response occurs. The
      cardiopulmonary baroreceptors, mechanically sensitive receptors that respond to
      changes in central blood volume and pressure, are strongly associated with
      changes in body position and upon activation elicit reflex sympathoinhibition.
      Here, we tested the hypothesis that postural changes modulate the sympathetically
      mediated cardiac response to PEI in humans. Beat-to-beat HR (electrocardiography)
      and blood pressure (finger photoplethysmography) were continuously measured, and
      cardiac function was assessed by echocardiography in 13 healthy men (21 +/- 3
      yr). After a 15-min rest period, 90-s static handgrip at 40% maximum voluntary
      contraction was performed followed by 3 min of PEI. Four trials were randomly
      conducted during either seated or supine position with and without beta1
      adrenergic blockade (25 mg atenolol). During PEI under control conditions, HR
      remained elevated from baseline in the seated [change (Delta): 4 +/- 1 beats/min]
      but not in the supine (change: -1 +/- 1 beats/min) position. Similarly, stroke
      volume and cardiac output were increased from baseline in the seated (?13.0 +/-
      2.4 ml and ?1.1 +/- 0.2 l/min, respectively) but not in the supine (?2.5 +/- 2.9
      ml and ?0.13 +/- 0.20 l/min, respectively) position. During beta1-adrenergic
      blockade, HR, stroke volume, and cardiac output remained unchanged in both
      conditions. We conclude that sympathetically mediated cardiac responses to PEI
      are influenced by changes in body position. These findings indicated that muscle
      metaboreflex and cardiopulmonary baroreflex have an interactive influence on the
      neural control of cardiovascular function in humans. NEW & NOTEWORTHY In the
      present study, we demonstrated that muscle metaboreflex activation increases
      heart rate, stroke volume, and cardiac output in the seated position but not in
      the supine position and not after beta1-adrenergic blockade. These findings
      indicate that sympathetically mediated cardiac responses to isolated muscle
      metaboreflex activation after exercise are modulated by central blood volume
      mobilization.

PMID- 29351474
TI  - The heart in lack of oxygen? A revisited method to improve cardiac performance ex
      vivo.

PMID- 29351475
TI  - Effect of heart rate reduction in pulmonary arterial hypertension.

PMID- 29351476
TI  - Human EndoC-betaH1 beta-cells form pseudoislets with improved glucose sensitivity
      and enhanced GLP-1 signaling in the presence of islet-derived endothelial cells.
AB  - Three-dimensional (3D) pseudoislets (PIs) can be used for the study of insulin
      producing beta-cells in free-floating islet-like structures similar to that of
      primary islets. Previously, we demonstrated the ability of islet-derived
      endothelial cells (iECs) to induce PIs using murine insulinomas, where PI
      formation enhanced insulin production and glucose responsiveness. In this report,
      we examined the ability of iECs to spontaneously induce the formation of free
      floating 3D PIs using the EndoC-betaH1 human beta-cell line murine MS1 iEC.
      Within 14 days, the coculturing of both cell types produced fully humanized EndoC
      betaH1 PIs with little to no contaminating murine iECs. The size and shape of
      these PIs were similar to primary human islets. iEC-induced PIs demonstrated
      reduced dysregulated insulin release under low glucose levels and higher insulin
      secretion in response to high glucose and exendin-4 [a glucagon-like peptide-1
      (GLP-1) analog] compared with monolayer cells cultured alone. Interestingly, iEC
      PIs were also better at glucose sensing in the presence of extendin-4 compared
      with PIs generated on a low-adhesion surface plate in the absence of iECs and
      showed an overall improvement in cell viability. iEC-induced PIs exhibited
      increased expression of key genes involved in glucose transport, glucose sensing,
      beta-cell differentiation, and insulin processing, with a concomitant decrease in
      glucagon mRNA expression. The enhanced responsiveness to exendin-4 was associated
      with increased protein expression of GLP-1 receptor and phosphokinase A. This
      rapid coculture system provides an unlimited number of human PIs with improved
      insulin secretion and GLP-1 responsiveness for the study of beta-cell biology.

PMID- 29351477
TI  - Mathematical analysis of circadian disruption and metabolic re-entrainment of
      hepatic gluconeogenesis: the intertwining entraining roles of light and feeding.
AB  - The circadian rhythms influence the metabolic activity from molecular level to
      tissue, organ, and host level. Disruption of the circadian rhythms manifests to
      the host's health as metabolic syndromes, including obesity, diabetes, and
      elevated plasma glucose, eventually leading to cardiovascular diseases.
      Therefore, it is imperative to understand the mechanism behind the relationship
      between circadian rhythms and metabolism. To start answering this question, we
      propose a semimechanistic mathematical model to study the effect of circadian
      disruption on hepatic gluconeogenesis in humans. Our model takes the light-dark
      cycle and feeding-fasting cycle as two environmental inputs that entrain the
      metabolic activity in the liver. The model was validated by comparison with data
      from mice and rat experimental studies. Formal sensitivity and uncertainty
      analyses were conducted to elaborate on the driving forces for hepatic
      gluconeogenesis. Furthermore, simulating the impact of Clock gene knockout
      suggests that modification to the local pathways tied most closely to the feeding
      fasting rhythms may be the most efficient way to restore the disrupted glucose
      metabolism in liver.

PMID- 29351478
TI  - Pentose phosphate pathway activity parallels lipogenesis but not antioxidant
      processes in rat liver.
AB  - The pentose phosphate pathway (PPP) is widely assumed to play a key role in both
      reductive biosynthesis and protection from oxidative stress because it is the
      major source of NADPH. However, little is known about the activity of the PPP in
      fatty liver, which is characterized by both oxidative stress and lipogenesis.
      This study was designed to test whether the PPP is active in parallel with
      lipogenesis and antioxidant processes in the fatty liver of whole animals. Eight-
      and 16-wk-old obese Zucker diabetic fatty rats and their lean littermates
      received [U-13C3]glycerol, and 13C labeling patterns of glucose and triglycerides
      were analyzed for the assessment of hepatic PPP activity and the potentially
      related processes simultaneously. Oxidative stress, antioxidant activity, and
      NADPH-producing enzymes in the liver were further examined. Both PPP activity and
      lipogenesis increased in the fatty liver of young obese Zucker rats but decreased
      together in older obese Zucker rats. As expected, lipid peroxidation measured by
      malondialdehyde increased in the fatty liver of obese Zucker rats at both ages.
      However, evidence for antioxidant processes such as [glutathione] or activities
      of glutathione reductase, glutathione peroxidase, and catalase was not altered.
      Hepatic PPP activity paralleled lipogenesis but was dissociated from biomarkers
      of oxidative stress or antioxidant processes. In summary, NADPH from the PPP was
      presumably consumed for reductive biosynthesis rather than antioxidant defense in
      the fatty liver.

PMID- 29351479
TI  - Using [2H]water to quantify the contribution of de novo palmitate synthesis in
      plasma: enabling back-to-back studies.
AB  - An increased contribution of de novo lipogenesis (DNL) may play a role in cases
      of dyslipidemia and adipose accretion; this suggests that inhibition of fatty
      acid synthesis may affect clinical phenotypes. Since it is not clear whether
      modulation of one step in the lipogenic pathway is more important than another,
      the use of tracer methods can provide a deeper level of insight regarding the
      control of metabolic activity. Although [2H]water is generally considered a
      reliable tracer for quantifying DNL in vivo (it yields a homogenous and
      quantifiable precursor labeling), the relatively long half-life of body water is
      thought to limit the ability of performing repeat studies in the same subjects;
      this can create a bottleneck in the development and evaluation of novel
      therapeutics for inhibiting DNL. Herein, we demonstrate the ability to perform
      back-to-back studies of DNL using [2H]water. However, this work uncovered special
      circumstances that affect the data interpretation, i.e., it is possible to obtain
      seemingly negative values for DNL. Using a rodent model, we have identified a
      physiological mechanism that explains the data. We show that one can use
      [2H]water to test inhibitors of DNL by performing back-to-back studies in higher
      species [i.e., treat nonhuman primates with platensimycin, an inhibitor of fatty
      acid synthase]; studies also demonstrate the unsuitability of [13C]acetate.

PMID- 29351480
TI  - Mechanistically different effects of fat and sugar on insulin resistance,
      hypertension, and gut microbiota in rats.
AB  - Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first
      manifestations of diet-induced metabolic alterations leading to Type 2 diabetes,
      while hypertension is the deadliest risk factor of cardiovascular disease. The
      roles of dietary fat and fructose in the development of IR, IGT, and hypertension
      are controversial. We tested the long-term effects of an excess of fat or sucrose
      (fructose/glucose) on healthy male Wistar-Kyoto (WKY) rats. Fat affects IR and
      IGT earlier than fructose through low-grade systemic inflammation evidenced by
      liver inflammatory infiltration, increased levels of plasma IL-6, PGE2, and
      reduced levels of protective short-chain fatty acids without triggering
      hypertension. Increased populations of gut Enterobacteriales and Escherichia coli
      may contribute to systemic inflammation through the generation of
      lipopolysaccharides. Unlike fat, fructose induces increased levels of
      diacylglycerols (lipid mediators of IR) in the liver, urine F2-isoprostanes
      (markers of systemic oxidative stress), and uric acid, and triggers hypertension.
      Elevated populations of Enterobacteriales and E. coli were only detected in rats
      given an excess of fructose at the end of the study. Dietary fat and fructose
      trigger IR and IGT in clearly differentiated ways in WKY rats: early low-grade
      inflammation and late direct lipid toxicity, respectively; gut microbiota plays a
      role mainly in fat-induced IR, and hypertension is independent of inflammation
      mediated IR. The results provide evidence that suggests that the combination of
      fat and sugar is potentially more harmful than fat or sugar alone when taken in
      excess.

PMID- 29351481
TI  - Regulation of glucose metabolism in nondiabetic, metabolically obese normal
      weight Asians.
AB  - Type 2 diabetes in Asia occurs largely in the absence of obesity. The
      metabolically obese normal-weight (MONW) phenotype refers to lean subjects with
      metabolic dysfunction that is typically observed in people with obesity and is
      associated with increased risk for diabetes. Previous studies evaluated MONW
      subjects who had greater body mass index (BMI) or total body fat than respective
      control groups, making interpretation of the results difficult. We evaluated
      insulin sensitivity (hyperinsulinemic-euglycemic clamp); insulin secretion (mixed
      meal with oral minimal modeling); intra-abdominal, muscle, and liver fat contents
      (magnetic resonance); and fasting and postprandial glucose and insulin
      concentrations in 18 MONW subjects and 18 metabolically healthy controls matched
      for age (43 +/- 3 and 40 +/- 3 yr; P = 0.52), BMI (both 22 +/- 1 kg/m2; P =
      0.69), total body fat (17 +/- 1 and 16 +/- 1 kg; P = 0.33), and sex (9 men and 9
      women in each group). Compared with controls, MONW subjects had an approximately
      twofold greater visceral adipose tissue volume and an approximately fourfold
      greater intrahepatic fat content (but similar muscle fat), 20-30% lower glucose
      disposal rates and insulin sensitivity, and 30-40% greater insulin secretion
      rates (all P < 0.05). The disposition index, fasting glucose, and HbA1c
      concentrations were not different between groups, whereas postprandial glucose
      and insulin concentrations were ~15% and ~65% greater, respectively, in MONW than
      control subjects (both P < 0.05). We conclude that the MONW phenotype is
      associated with accumulation of fat in the intra-abdominal area and the liver,
      profound insulin resistance, but also a robust beta-cell insulin secretion
      response that compensates for insulin resistance and helps maintain glucose
      homeostasis.

PMID- 29351482
TI  - Suppression of gut dysbiosis reverses Western diet-induced vascular dysfunction.
AB  - Vascular dysfunction represents a critical preclinical step in the development of
      cardiovascular disease. We examined the role of the gut microbiota in the
      development of obesity-related vascular dysfunction. Male C57BL/6J mice were fed
      either a standard diet (SD) ( n = 12) or Western diet (WD) ( n = 24) for 5 mo,
      after which time WD mice were randomized to receive either unsupplemented
      drinking water or water containing a broad-spectrum antibiotic cocktail (WD +
      Abx) ( n = 12/group) for 2 mo. Seven months of WD caused gut dysbiosis, increased
      arterial stiffness (SD 412.0 +/- 6.0 vs. WD 458.3 +/- 9.0 cm/s, P < 0.05) and
      endothelial dysfunction (28% decrease in max dilation, P < 0.05), and reduced l
      NAME-inhibited dilation. Vascular dysfunction was accompanied by significant
      increases in circulating LPS-binding protein (LBP) (SD 5.26 +/- 0.23 vs. WD 11 +/
      0.86 ug/ml, P < 0.05) and interleukin-6 (IL-6) (SD 3.27 +/- 0.25 vs. WD 7.09 +/-
      1.07 pg/ml, P < 0.05); aortic expression of phosphorylated nuclear factor-kappaB
      (p-NF-kappaB) ( P < 0.05); and perivascular adipose expression of NADPH oxidase
      subunit p67phox ( P < 0.05). Impairments in vascular function correlated with
      reductions in Bifidobacterium spp. Antibiotic treatment successfully abrogated
      the gut microbiota and reversed WD-induced arterial stiffness and endothelial
      dysfunction. These improvements were accompanied by significant reductions in
      LBP, IL-6, p-NF-kappaB, and advanced glycation end products (AGEs), and were
      independent from changes in body weight and glucose tolerance. These results
      indicate that gut dysbiosis contributes to the development of WD-induced vascular
      dysfunction, and identify the gut microbiota as a novel therapeutic target for
      obesity-related vascular abnormalities.

PMID- 29351483
TI  - Prenatal exposure to diesel exhaust PM2.5 causes offspring beta cell dysfunction
      in adulthood.
AB  - Environmental stressors that encounter in early-life and cause abnormal fetal
      and/or neonatal development may increase susceptibility to non-communicable
      diseases such as diabetes. Maternal exposure to ambient fine particulate matter
      (PM2.5) is associated with various fetal abnormalities, suggesting that it may
      program offspring's susceptibility to diabetes. In the present study, we
      therefore examined whether maternal exposure to diesel exhaust PM2.5 (DEP), one
      of the major sources of ambient PM2.5 in urban areas, programs adult offspring's
      glucose metabolism. Female C57Bl/6J mice were intratracheally instilled with DEP
      or vehicle throughout a 7-wk preconceptional period, gestation, and lactation,
      and the glucose homeostasis of their adult male offspring was assessed.
      Intraperitoneal glucose tolerance test (IPGTT) revealed that the maternal
      exposure to DEP significantly impaired adult male offspring's glucose tolerance.
      Unexpectedly, it did not influence their insulin sensitivity, whereas it
      significantly decreased their glucose-induced insulin secretion (GIIS). This
      deficit in insulin secretion was corroborated by their significant decrease in
      arginine-induced insulin secretion. Histological analysis demonstrated that the
      deficit in insulin secretion was accompanied by the decrease in pancreatic islet
      and beta cell sizes. To differentiate the effects of maternal exposure to DEP
      before birth and during lactation, some offspring were cross-fostered once born.
      We did not observe any significant effect of cross-fostering on the glucose
      homeostasis of adult male offspring and the function and morphology of their beta
      cells. Prenatal exposure to DEP programs the morphology and function of beta
      cells and thus homeostatic regulation of glucose metabolism in adult male
      offspring.

PMID- 29351484
TI  - The serum metabolomics signature of type 2 diabetes is obscured in Alzheimer's
      disease.
AB  - There is evidence for systemic metabolic impairment in Alzheimer's disease (AD),
      and type 2 diabetes (T2D) increases AD risk. Although studies analyzing blood
      metabolomics signatures have shown differences between cognitively healthy (CH)
      and AD subjects, these signatures have not been compared with individuals with
      T2D. We utilized untargeted analysis platforms (primary metabolism and complex
      lipids) to characterize the serum metabolome of 126 overnight-fasted elderly
      subjects classified into four groups based upon AD status (CH or AD) and T2D
      status [nondiabetic (ND) or T2D]. Cognitive diagnosis groups were a priori
      weighted equally with T2D subjects. We hypothesized that AD subjects would
      display a metabolic profile similar to cognitively normal elderly individuals
      with T2D. However, partial least squares-discriminant analysis (PLS-DA) modeling
      resulted in poor classification across the four groups (<50% classification
      accuracy of test subjects). Binary classification of AD vs. CH was poor, but
      binary classification of T2D vs. ND was good, providing >79.5% and >76.9%
      classification accuracy for held-out samples using primary metabolism and complex
      lipids, respectively. When modeling was limited to CH subjects, T2D
      discrimination improved for the primary metabolism platform (>89.5%) and remained
      accurate for complex lipids (>73% accuracy). Greater abundances of glucose, fatty
      acids (C20:2), and phosphatidylcholines and lower abundances of glycine,
      maleimide, octanol, and tryptophan, cholesterol esters, phosphatidylcholines, and
      sphingomyelins were identified in CH subjects with T2D relative to those without
      T2D. In contrast, T2D was not accurately discriminated within AD subjects.
      Results herein suggest that AD may obscure the typical metabolic phenotype of
      T2D.

PMID- 29351485
TI  - Insulin signaling displayed a differential tissue-specific response to low-dose
      dihydrotestosterone in female mice.
AB  - Hyperandrogenemia and hyperinsulinemia are believed to play prominent roles in
      polycystic ovarian syndrome (PCOS). We explored the effects of low-dose
      dihydrotestosterone (DHT), a model of PCOS, on insulin signaling in metabolic and
      reproductive tissues in a female mouse model. Insulin resistance in the energy
      storage tissues is associated with type 2 diabetes. Insulin signaling in the
      ovaries and pituitary either directly or indirectly stimulates androgen
      production. Energy storage and reproductive tissues were isolated and molecular
      assays were performed. Livers and white adipose tissue (WAT) from DHT mice
      displayed lower mRNA and protein expression of insulin signaling intermediates.
      However, ovaries and pituitaries of DHT mice exhibited higher expression levels
      of insulin signaling genes/proteins. Insulin-stimulated p-AKT levels were blunted
      in the livers and WAT of the DHT mice but increased or remained the same in the
      ovaries and pituitaries compared with controls. Glucose uptake decreased in liver
      and WAT but was unchanged in pituitary and ovary of DHT mice. Plasma membrane
      GLUTs were decreased in liver and WAT but increased in ovary and pituitary of DHT
      mice. Skeletal muscle insulin-signaling genes were not lowered in DHT mice
      compared with control. DHT mice did not display skeletal muscle insulin
      resistance. Insulin-stimulated glucose transport increased in skeletal muscles of
      DHT mice compared with controls. DHT mice were hyperinsulinemic. However, the
      differential mRNA and protein expression pattern was independent of
      hyperinsulinemia in cultured hepatocytes and pituitary cells. These findings
      demonstrate a differential effect of DHT on the insulin-signaling pathway in
      energy storage vs. reproductive tissues independent of hyperinsulinemia.

PMID- 29351486
TI  - Different physiological roles of insulin receptors in mediating nutrient
      metabolism in zebrafish.
AB  - Insulin, the most potent anabolic hormone, is critical for somatic growth and
      metabolism in vertebrates. Type 2 diabetes, which is the primary cause of
      hyperglycemia, results from an inability of insulin to signal glycolysis and
      gluconeogenesis. Our previous study showed that double knockout of insulin
      receptor a ( insra) and b ( insrb) caused beta-cell hyperplasia and lethality
      from 5 to 16 days postfertilization (dpf) (Yang BY, Zhai G, Gong YL, Su JZ, Han
      D, Yin Z, Xie SQ. Sci Bull (Beijing) 62: 486-492, 2017). In this study, we
      characterized the physiological roles of Insra and Insrb, in somatic growth and
      fueling metabolism, respectively. A high-carbohydrate diet was provided for
      insulin receptor knockout zebrafish from 60 to 120 dpf to investigate phenotype
      inducement and amplification. We observed hyperglycemia in both insra-/- fish and
      insrb-/- fish. Impaired growth hormone signaling, increased visceral adiposity,
      and fatty liver were detected in insrb-/- fish, which are phenotypes similar to
      the lipodystrophy observed in mammals. More importantly, significantly diminished
      protein levels of P-PPARalpha, P-STAT5, and IGF-1 were also observed in insrb-/-
      fish. In insra-/- fish, we observed increased protein content and decreased lipid
      content of the whole body. Taken together, although Insra and Insrb show
      overlapping roles in mediating glucose metabolism through the insulin-signaling
      pathway, Insrb is more prone to promoting lipid catabolism and protein synthesis
      through activation of the growth hormone-signaling pathway, whereas Insra
      primarily acts to promote lipid synthesis via glucose utilization.

PMID- 29351487
TI  - Contribution of parasympathetic muscarinic augmentation of insulin secretion to
      olanzapine-induced hyperinsulinemia.
AB  - Atypical antipsychotic drugs have been associated with the development of obesity
      and diabetes. In particular, olanzapine can induce peripheral insulin resistance
      and compensatory hyperinsulinemia independent of weight gain or psychiatric
      disease. To determine if this compensatory increase in insulin is mediated by
      parasympathetic muscarinic stimulation, we randomized 15 healthy subjects 2:1 to
      receive double-blind olanzapine or placebo for 9 days under diet- and activity
      controlled inpatient conditions. Before and after 7 days of study drug
      administration, subjects underwent frequently sampled intravenous glucose
      tolerance tests with either saline or atropine infused on subsequent days to
      assess insulin secretion and hepatic insulin extraction in the absence or
      presence of muscarinic blockade. We found that olanzapine led to an increase in
      the acute insulin response to glucose, which was not seen with placebo, and was
      attenuated in the olanzapine group by atropine. Deconvolution of C-peptide data
      confirmed an increase in insulin secretion with olanzapine, which was blocked by
      atropine, with a modest reduction in hepatic insulin extraction with olanzapine.
      These results support the contribution of muscarinic augmentation of insulin
      secretion to olanzapine-induced hyperinsulinemia, and provide a mechanism for the
      compensatory hyperinsulinemia that normally serves to prevent deterioration of
      glucose tolerance under conditions of metabolic challenge.

PMID- 29351488
TI  - Measurement of postprandial glucose fluxes in response to acute and chronic
      endurance exercise in healthy humans.
AB  - The effect of endurance exercise on enhancing insulin sensitivity and glucose
      flux has been well established with techniques such as the hyperinsulinemic
      clamp. Although informative, such techniques do not emulate the physiological
      postprandial state, and it remains unclear how exercise improves postprandial
      glycaemia. Accordingly, combining mixed-meal tolerance testing and the triple
      stable isotope glucose tracer approach, glucose fluxes [rates of meal glucose
      appearance (Ra), disposal (Rd), and endogenous glucose production (EGP)] were
      determined following acute endurance exercise (1 h cycling; ~70% Vo2max) and 4 wk
      of endurance training (cycling 5 days/wk). Training was associated with a modest
      increase in Vo2max (~7%, P < 0.001). Postprandial glucose and insulin responses
      were reduced to the same extent following acute and chronic training.
      Interestingly, this was not accompanied by changes to rates of meal Ra, Rd, or
      degree of EGP suppression. Glucose clearance (Rd relative to prevailing glucose)
      was, however, enhanced with acute and chronic exercise. Furthermore, the duration
      of EGP suppression was shorter with acute and chronic exercise, with EGP
      returning toward fasting levels more rapidly than pretraining conditions. These
      findings suggest that endurance exercise influences the efficiency of the
      glucoregulatory system, where pretraining rates of glucose disposal and
      production were achieved at lower glucose and insulin levels. Notably, there was
      no influence of chronic training over and above that of a single exercise bout,
      providing further evidence that glucoregulatory benefits of endurance exercise
      are largely attributed to the residual effects of the last exercise bout.

PMID- 29351489
TI  - Cooperative function of Pdx1 and Oc1 in multipotent pancreatic progenitors
      impacts postnatal islet maturation and adaptability.
AB  - The transcription factors pancreatic and duodenal homeobox 1 (Pdx1) and onecut1
      (Oc1) are coexpressed in multipotent pancreatic progenitors (MPCs), but their
      expression patterns diverge in hormone-expressing cells, with Oc1 expression
      being extinguished in the endocrine lineage and Pdx1 being maintained at high
      levels in beta-cells. We previously demonstrated that cooperative function of
      these two factors in MPCs is necessary for proper specification and
      differentiation of pancreatic endocrine cells. In those studies, we observed a
      persistent decrease in expression of the beta-cell maturity factor MafA. We
      therefore hypothesized that Pdx1 and Oc1 cooperativity in MPCs impacts postnatal
      beta-cell maturation and function. Here our model of Pdx1-Oc1 double
      heterozygosity was used to investigate the impact of haploinsufficiency for both
      of these factors on postnatal beta-cell maturation, function, and adaptability.
      Examining mice at postnatal day (P) 14, we observed alterations in pancreatic
      insulin content in both Pdx1 heterozygotes and double heterozygotes. Gene
      expression analysis at this age revealed significantly decreased expression of
      many genes important for glucose-stimulated insulin secretion (e.g., Glut2,
      Pcsk1/2, Abcc8) exclusively in double heterozygotes. Analysis of P14 islets
      revealed an increase in the number of mixed islets in double heterozygotes. We
      predicted that double-heterozygous beta-cells would have an impaired ability to
      respond to stress. Indeed, we observed that beta-cell proliferation fails to
      increase in double heterozygotes in response to either high-fat diet or placental
      lactogen. We thus report here the importance of cooperation between regulatory
      factors early in development for postnatal islet maturation and adaptability.

PMID- 29351492
TI  - Moyamoya (????): When cerebral arteries go up in smoke.

PMID- 29351491
TI  - Pneumococcal meningitis trends after pneumococcal conjugate vaccine introduction
      in Colombia: An interrupted time-series analysis.
AB  - Colombia introduced mass pneumococcal conjugate vaccination at the end of 2011.
      Using 2005-2015 surveillance data, we conducted a retrospective interrupted time
      series analysis. A significant trend towards reduced monthly was observed in the
      post-vaccination period (2012-2015) compared with the expected rate, reaching in
      2015 a reduction of 90.5% of pneumococcal meningitis. This trend was not observed
      for control diseases.

PMID- 29351490
TI  - Significant improvement in cardiometabolic health in healthy nonobese individuals
      during caloric restriction-induced weight loss and weight loss maintenance.
AB  - Calorie restriction (CR) triggers benefits for healthspan including decreased
      risk of cardiometabolic disease (CVD). In an ancillary study to CALERIE 2, a 24
      mo 25% CR study, we assessed the cardiometabolic effects of CR in 53 healthy,
      nonobese (BMI: 22-28 kg/m2) men ( n = 17) and women ( n = 36). The aim of this
      study was to investigate whether CR can reduce risk factors for CVD and insulin
      resistance in nonobese humans and, moreover, to assess whether improvements are
      exclusive to a period of weight loss or continue during weight maintenance.
      According to the energy balance method, the 25% CR intervention ( n = 34)
      produced 16.5 +/- 1.5% (mean +/- SE) and 14.8 +/- 1.5% CR after 12 and 24 mo
      (M12, M24), resulting in significant weight loss (M12 -9 +/- 0.5 kg, M24 -9 +/-
      0.5 kg, P < 0.001). Weight was maintained in the group that continued their
      habitual diet ad libitum (AL, n = 19). In comparison to AL, 24 mo of CR decreased
      visceral (-0.5 +/- 0.01 kg, P < 0.0001) and subcutaneous abdominal adipose tissue
      (-1.9 +/- 0.2kg, P < 0.001) as well as intramyocellular lipid content (-0.11 +/-
      0.05%, P = 0.031). Furthermore, CR decreased blood pressure (SBP -8 +/- 3 mmHg, P
      = 0.005; DBP -6 +/- 2 mmHg, P < 0.001), total cholesterol (-13.6 +/- 5.3 mg/dl, P
      = 0.001), and LDL-cholesterol (-12.9 +/- 4.4 mg/dl, P = 0.005), and the 10-yr
      risk of CVD-disease was reduced by 30%. Homeostasis model assessment of insulin
      resistance (HOMA-IR) decreased during weight loss in the CR group (-0.46 +/-
      0.15, P = 0.003), but this decrease was not maintained during weight maintenance
      (-0.11 +/- 0.15, P = 0.458). In conclusion, sustained CR in healthy, nonobese
      individuals is beneficial in improving risk factors for cardiovascular and
      metabolic disease such as visceral adipose tissue mass, ectopic lipid
      accumulation, blood pressure, and lipid profile, whereas improvements in insulin
      sensitivity were only transient.

PMID- 29351493
TI  - Test-retest reliability of the unsupported upper-limb exercise test (UULEX) and 6
      min peg board ring test (6PBRT) in healthy adult individuals.
AB  - BACKGROUND: The unsupported upper-limb exercise (UULEX) and 6-min peg board ring
      tests (6PBRTs) have been developed to measure peak unsupported arm exercise
      capacity and arm endurance, respectively, in individuals with chronic obstructive
      pulmonary disease. These tests are valid and reproducible in this population;
      however, the reproducibility of healthy adults is currently unknown. OBJECTIVE:
      To determine the within-day test-retest reliability of the UULEX and 6PBRT in
      healthy adults. METHOD: The study included 41 healthy adults, aged 38.3 +/- 17.9
      years old, who performed both tests, twice each on the same day, with a 30-min
      rest in between. Before and immediately after the tests, blood pressure (BP),
      heart rate (HR), perception of exertion, and arm fatigue were measured. Time to
      perform the test and number of rings moved were recorded for the UULEX and 6PBRT,
      respectively. RESULTS: The UULEX was reproducible on Bland-Altman analysis with
      lower and upper limits of agreement: 2.40 and -2.49 min, respectively (bias = 
      0.05; p = 0.817) and intraclass correlation coefficient (ICC) = 0.85 (p < 0.0001)
      for time in minutes for the first and second tests. The 6PBRT was not
      reproducible on Bland-Altman analysis with lower and upper limits of agreement of
      31.64 and -114.54 (bias = -41.45; p < 0.0001) and ICC = 0.91 (p < 0.0001) for the
      number of rings moved. CONCLUSION: UULEX is a reliable test in healthy adults.
      Only one test is adequate when measuring peak unsupported arm exercise capacity
      using the UULEX in healthy adults, while more than two tests may be needed to
      measure arm endurance using the 6PBRT.

PMID- 29351494
TI  - Factors Associated with Sarcopenia in Patients with Colorectal Cancer.
AB  - Introduction; Sarcopenia are frequently observed in cancer patients and was
      associated with poor prognosis. Objectives; to determine the association of
      nutritional status, body composition, and clinic parameters with sarcopenia in
      patients with colorectal cancer (CRC). Methods; We conducted a cross-sectional
      study of 197 patients with CRC. The sarcopenia elements, including lumbar
      skeletal muscle index (SMI), handgrip strength, and gait speed were measured. The
      SMI was assessed by computed tomography at third lumbar vertebra. Phase angle
      (PA), serum albumin (SAlb), muscle attenuation (MA), and the scored patient
      generated subjective global assessment (PG-SGA) were also evaluated. Univariate
      and multivariate analysis of factors associated with sarcopenia were performed.
      Results; Sarcopenia was present in 29 of 195 patients (15%) and was significantly
      correlated with advance age, lower body mass index (BMI), SAlb, PA, MA, higher PG
      SGA score, and malnutrition (PG-SGA B). In univariate analysis, age, BMI, SAlb,
      PA, MA, PG-SGA score, and malnutrition (PG-SGA B) were associated with
      sarcopenia. Multivariable analysis revealed that BMI, SAlb, PA, MA, and PG-SGA
      score were independent predictors of sarcopenia. Conclusion; BMI, SAlb, PA, MA,
      and PG-SGA score were independent predictors of sarcopenia in patients with CRC.

PMID- 29351495
TI  - Implementing Prehospital Evidence-Based Guidelines: A Systematic Literature
      Review.
AB  - OBJECTIVE: As prehospital research advances, more evidence-based guidelines
      (EBGs) are implemented into emergency medical services (EMS) practice. However,
      incomplete or suboptimal prehospital EBG implementation may hinder improvement in
      patient outcomes. To inform future efforts, this study's objective was to review
      existing evidence pertaining to prehospital EBG implementation methods. METHODS:
      This study was a systematic literature review and evaluation following the
      Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)
      methodology. PubMed, EMBASE, Scopus, and Google Advanced Search were searched
      without language or publication date filters for articles addressing prehospital
      EBG implementation. Conference proceedings, textbooks, and non-English articles
      were excluded. GRADE was applied to the remaining articles independently by three
      of five study investigators. Study characteristics and salient findings from the
      included articles are reported. RESULTS: The systematic literature review
      identified 1,367 articles, with 41 meeting inclusion criteria. Most articles
      described prehospital EBG implementation (n = 24, 59%), or implementation
      barriers (n = 13, 32%). Common study designs were statement documents (n = 12,
      29%), retrospective cohort studies (n = 12, 29%), and cross-sectional studies (n
      = 9, 22%). Using GRADE, evidence quality was rated low (n = 18, 44%), or very low
      (n = 23, 56%). Salient findings from the articles included: (i) EBG adherence and
      patient outcomes depend upon successful implementation, (ii) published studies
      generally lack detailed implementation methods, (iii) EBG implementation takes
      longer than planned (mostly for EMS education), (iv) EMS systems' heterogeneity
      affects EBG implementation, and (v) multiple barriers limit successful
      implementation (e.g., financial constraints, equipment purchasing, coordination
      with hospitals, and regulatory agencies). This review found no direct evidence
      for best prehospital EBG implementation practices. There were no studies
      comparing implementation methods or implementation in different prehospital
      settings (e.g., urban vs. rural, advanced vs. basic life support). CONCLUSIONS:
      While prehospital EBG implementation barriers are well described, there is a
      paucity of evidence for optimal implementation methods. For scientific advances
      to reach prehospital patients, EBG development efforts must translate into EMS
      practice. Future research should consider comparing implementation methodologies
      in different prehospital settings, with a goal of defining detailed, reproducible
      best practices.

PMID- 29351496
TI  - Implementation of a Prehospital Protocol Change For Asthmatic Children.
AB  - BACKGROUND: Respiratory distress due to asthma is a common reason for pediatric
      emergency medical services (EMS) transports. Timely initiation of asthma
      treatment, including glucocorticoids, improves hospital outcomes. The impact of
      EMS-administered glucocorticoids on hospital-based outcomes for pediatric asthma
      patients is unknown. OBJECTIVE: The objective of this study was to evaluate the
      effect of an evidence-based pediatric EMS asthma protocol update, inclusive of
      oral glucocorticoid administration, on time to hospital discharge. METHODS: This
      was a retrospective cohort study of children (2-18 years) with an acute asthma
      exacerbation transported by an urban EMS system to 10 emergency departments over
      2 years. The investigators implemented an EMS protocol update one year into the
      study period requiring glucocorticoid administration for all patients, with the
      major change being inclusion of oral dexamethasone (0.6 mg/kg, max. dose = 10
      mg). Protocol implementation included mandatory paramedic training. Data was
      abstracted from linked prehospital and hospital records. Continuous data were
      compared before and after the protocol change with the Mann-Whitney test, and
      categorical data were compared with the Pearson chi2 test. RESULTS: During the
      study period, 482 asthmatic children met inclusion criteria. After the protocol
      change, patients were more likely to receive a prehospital glucocorticoid (11%
      vs. 18%, p = 0.02). Median total hospital time after the protocol change
      decreased from 6.1 hours (95% CI: 5.4-6.8) to 4.5 hours (95% CI: 4.2-4.8), p <
      0.001. Total care time, defined as time from ambulance arrival to hospital
      discharge, also decreased [6.6 hours (95% CI: 5.8-7.3) vs. 5.2 hours (95% CI: 4.8
      5.6), p = 0.01]. Overall, patients were less likely to be admitted to the
      hospital (30% vs. 21%, p = 0.02) after the change. Those with more severe
      exacerbations were less likely to be admitted to a critical care unit (82% vs.
      44%, p = 0.02) after the change, rather than an acute care floor. CONCLUSIONS:
      Prehospital protocol change for asthmatic children is associated with shorter
      total hospital and total care times. This protocol change was also associated
      with decreased hospitalization rates and less need for critical care in those
      hospitalized. Further study is necessary to determine if other factors also
      contributed.

PMID- 29351497
TI  - Screen Targeting Lung and Prostate Cancer Oncogene Identifies Novel Inhibitors of
      RGS17 and Problematic Chemical Substructures.
AB  - Regulator of G protein signaling (RGS) proteins temporally regulate
      heterotrimeric G protein signaling cascades elicited by G protein-coupled
      receptor activation and thus are essential for cell homeostasis. The
      dysregulation of RGS protein expression has been linked to several pathologies,
      spurring discovery efforts to identify small-molecule inhibitors of these
      proteins. Presented here are the results of a high-throughput screening (HTS)
      campaign targeting RGS17, an RGS protein reported to be inappropriately
      upregulated in several cancers. A screen of over 60,000 small molecules led to
      the identification of five hit compounds that inhibit the RGS17-Galphao protein
      protein interaction. Chemical and biochemical characterization demonstrated that
      three of these hits inhibited the interaction through the decomposition of parent
      compound into reactive products under normal chemical library storage/usage
      conditions. Compound substructures susceptible to decomposition are reported and
      the decomposition process characterized, adding to the armamentarium of tools
      available to the screening field, allowing for the conservation of resources in
      follow-up efforts and more efficient identification of potentially decomposed
      compounds. Finally, analogues of one hit compound were tested, and the results
      establish the first ever structure-activity relationship (SAR) profile for a
      small-molecule inhibitor of RGS17.

PMID- 29351498
TI  - High-power diode laser on management of drug-induced gingival overgrowth: Report
      of two cases and long-term follow-up.
AB  - BACKGROUND: Drug-induced gingival overgrowth (DIGO) is attributed mainly to the
      prolonged use of calcium channel blocking agents, anticonvulsants, and anti
      calcineurin inhibitors . The management of DIGO depends on the severity of the
      disease and includes surgical intervention and plaque control. Compared to
      conventional surgical treatment, the recent literature data have shown that
      gingivectomy using a high-power laser (HPL) is a short and easy procedure, which
      results in minimal postoperative discomfort and greater patient accep- tance.
      OBJECTIVE AND METHODS: The purpose of this study was to report two cases of
      recurrent DIGO treated surgically using HPL (lambda 808nm, 1.5W). RESULTS:
      Minimal bleeding and discomfort were observed during surgery, and patients
      reported no pain or bleeding after the procedure. After 1 year of follow-up,
      patients presented a minimal increase of gingival volume, indicating that laser
      technology can improve the efficiency and prognosis of DIGO. CONCLUSIONS: The HPL
      was able to preventing hemorrhage and improving the patient's collaboration with
      the treatment and quality of life.

PMID- 29351499
TI  - Graduate speech-language pathology students' initial self-perceptions of skills
      critical for interprofessional practice.
AB  - Interprofessional collaborative practice is critical for quality service
      delivery. Given the limited research on speech-language pathology (SLP) students'
      interprofessional knowledge and skills, this investigation assessed graduate SLP
      students' self-perceived interprofessional competence and their perceptions of
      roles of other professionals. Fifty-eight SLP students completed two validated
      surveys at the beginning of the first or second semester of graduate school.
      Collectively, the students rated themselves positively on communication,
      teamwork, attitudes toward interprofessional learning, and professional
      relationships. They rated the interactions of other professionals negatively. No
      significant differences were found between first- and second-semester students on
      communication, teamwork, and attitudes toward interprofessional learning. First
      semester students rated interprofessional interactions and personal
      interprofessional relationships more positively than second-semester students.
      Overall, the students rated other professionals positively. These data describe
      the initial self-perceived interprofessional competencies of SLP students early
      in their master's program, providing direction in designing interprofessional
      experiences for SLP students and practicing clinicians.

PMID- 29351501
TI  - Pediatric Anaphylaxis in the Prehospital Setting: Incidence, Characteristics, and
      Management.
AB  - OBJECTIVE: Although hospital presentations for pediatric anaphylaxis have been
      described in the literature, a minimal amount is known regarding the incidence,
      characteristics, and management of pediatric anaphylaxis presenting to emergency
      medical services (EMS). METHODS: We performed a retrospective observational study
      of pediatrics (<=16 years) presenting to EMS in Victoria, Australia. Patients
      with suspected anaphylaxis were included if they were treated with epinephrine
      before or after EMS arrival. We used descriptive statistics to compare baseline
      characteristics and linear regression to assess trends in incidence over time.
      RESULTS: Between July 2008 and June 2016, we identified 2,137 pediatric
      anaphylaxis presentations. Overall, 59% were male and 70% had pre-existing
      anaphylaxis. The age-adjusted incidence increased over the study period, from
      11.8 presentations per 100,000 person-years in 2008-09 to 38.7 in 2015-16 (p for
      trend < 0.001). Common suspected allergens included nuts (52%) and dairy/milk
      formula (17%). In total, 1,333 (62%) patients received epinephrine via an
      autoinjector, and 51 (2%) from a doctor before EMS arrival. When compared to
      patients receiving epinephrine after EMS arrival, patients treated prior were
      more likely to present with vital signs within normal limits, including heart
      rate (66% vs. 84%, p < 0.001), systolic blood pressure (77% vs. 93%, p < 0.001)
      and respiratory rate (79% vs. 91%, p < 0.001). The most common EMS interventions
      were intramuscular epinephrine (45%) and inhaled salbutamol (14%). Three out-of
      hospital cardiac arrests were observed, two of whom received endotracheal
      intubation. CONCLUSION: The incidence of prehospital pediatric anaphylaxis is
      increasing significantly. Despite this, most patients are hemodynamically stable
      on presentation and few require emergency treatments beyond the administration of
      intramuscular epinephrine.

PMID- 29351500
TI  - Differential Learning as a Key Training Approach to Improve Creative and Tactical
      Behavior in Soccer.
AB  - PURPOSE: The aim of this study was to identify the effects of a differential
      learning program, embedded in small-sided games, on the creative and tactical
      behavior of youth soccer players. Forty players from under-13 (U13) and under-15
      (U15) were allocated into control and experimental groups and were tested using a
      randomized pretest to posttest design using small-sided games situations. METHOD:
      The experimental group participated in a 5-month differential-learning program
      embodied in small-sided games situations, while the control group participated in
      a typical small-sided games training program. In-game creativity was assessed
      through notational analyses of the creative components, and the players'
      positional data were used to compute tactical-derived variables. RESULTS: The
      findings suggested that differential learning facilitated the development of
      creative components, mainly concerning attempts (U13, small; U15, small),
      versatility (U13, moderate; U15, small), and originality (U13, unclear; U15,
      small) of players' actions. Likewise, the differential-learning approach provided
      a decrease in fails during the game in both experimental groups (moderate).
      Moreover, differential learning seemed to favor regularity in pitch-positioning
      behavior for the distance between players' dyads (U13, small; U15, small), the
      distance to the team target (U13, moderate; U15, small), and the distance to the
      opponent target (U13, moderate; U15, small). CONCLUSIONS: The differential
      learning program stressed creative and positional behavior in both age groups
      with a distinct magnitude of effects, with the U13 players demonstrating higher
      improvements over the U15 players. Overall, these findings confirmed that the
      technical variability promoted by differential learning nurtures regularity of
      positioning behavior.

PMID- 29351502
TI  - Malignant Melanoma: How Do We Meet the Needs of Young People and Their Families?

PMID- 29351503
TI  - Prehospital Intubation: Further Confounders in Trial Results.

PMID- 29351504
TI  - A systematic literature review of physiotherapy and rehabilitation approaches to
      lower-limb amputation.
AB  - BACKGROUND: Successful use of prostheses after lower-limb amputation (LLA)
      depends on undergoing physiotherapy and rehabilitation both physically and
      psychologically. The aim of this systematic literature review is to
      systematically review the scientific evidence regarding prosthetic rehabilitation
      and physiotherapy after LLA. METHODS: A systematic literature search was
      conducted using PubMed, Web of Science, Cochrane, CINAHL, EMBASE, SCOPUS, and EMB
      Reviews databases on December 31, 2015. Studies with the search keywords were
      identified and independently assessed by reviewers. The search yielded 403
      potentially relevant articles after the removal of duplicates. Of these, only
      nine articles met the inclusion criteria. All studies were original articles, one
      of which was a randomized controlled study. Different measurement methods were
      used and positive results in terms of functional status, weight-lifting capacity
      with prosthesis, walking and balance ability, and acute care process were gained
      with a physiotherapy program. Conventional methods still possess high importance;
      however, it is safe to say that virtual reality and software-based programs for
      rehabilitation are increasingly being developed and getting more and more
      support. DISCUSSION: LLA rehabilitation is a topic that requires the focus of
      current and future studies; evidence-based studies are required on the approaches
      to rehabilitation for specific LLA groups.

PMID- 29351505
TI  - Helping, mediating, and gaining recognition: The everyday identity work of
      Romanian health social workers.
AB  - Health social work is a field with challenges, opportunities, and ways of
      professing social work that may vary between different national contexts. In this
      article, we look at how Romanian health social workers construct their
      professional identity through their everyday identity work. Drawing on a
      qualitative study based on interviews with 21 health social workers working in
      various organizational contexts, we analyze what health social workers say they
      do and how this shapes their self-conception as professionals. Four main themes
      emerged from participants' descriptions: being a helping professional, being a
      mediator, gaining recognition, and contending with limits. Through these themes,
      participants articulated the everyday struggles and satisfactions specific to
      working as recently recognized professionals in Romanian health and welfare
      systems not always supportive of their work.

PMID- 29351506
TI  - Scaling Constraints in Junior Tennis: The Influence of Net Height on Skilled
      Players' Match-Play Performance.
AB  - PURPOSE: The net height in tennis (0.91 m) is approximately 50% of a professional
      tennis player's height. Children are also expected to play with this net height,
      even though it is approximately 70% of the average 10-year-old's height. This
      study examined the immediate effect of lowering net height on the performance
      characteristics of skilled junior tennis players aged 10 years and younger.
      METHOD: Sixteen players were matched in 8 pairs of even tennis ability and same
      sex. Each pair played 25-min singles matches in 4 conditions that varied in net
      height (0.91 m, 0.78 m, 0.65 m, and 0.52 m). Match-play characteristics were
      analyzed via video replay. RESULTS: Results showed that lowering the net height
      to 0.65 m and 0.52 m led to players adopting a more attacking style of play, as
      evidenced by a significant increase in the number of winners without a
      commensurate increase in errors and more shots struck inside the baseline. Lower
      nets also led to a greater percentage of successful first serves. The lowest net
      (0.52 m), however, reduced rally length significantly and therefore decreased
      hitting opportunities. CONCLUSION: These results offer support for equipment
      scaling to enhance match-play performance for skilled junior tennis players. We
      propose that current net height recommendations for junior tennis should be
      revised.

PMID- 29351507
TI  - "I Smoke Like This to Suppress These Issues That Are Flaws of My Character":
      Challenges and Facilitators of Cessation Among Smokers With Bipolar Disorder.
AB  - OBJECTIVE: Smokers with bipolar disorder (BD) have low rates of successful
      quitting, yet no prior studies have evaluated the process of quitting among these
      smokers in the context of a current quit attempt. To facilitate development of
      more effective interventions, we conducted a qualitative exploration of
      challenges and facilitators of quitting in an intervention study for smokers with
      BD. METHODS: Participants were adult daily smokers with BD (n = 10) who completed
      a 10-week smoking cessation intervention consisting of Acceptance and Commitment
      Therapy (ACT) and nicotine patch. We administered semistructured interviews
      focused on the quitting process at the end of treatment and used inductive
      content analysis to extract themes. RESULTS: Emergent themes representing
      challenges of quitting included social impediments, lack of awareness, avoidance,
      maladaptive beliefs, ambivalence, benefits of smoking, and difficulties with
      nicotine replacement. Themes representing change facilitators included positive
      treatment effects (ACT-specific, nonspecific, and nicotine patch-related), coping
      behaviors, reasons to quit, changes in self-perception, and social benefits.
      CONCLUSIONS: Results suggest a need for assistance with obtaining social support
      and handling social impediments, interrupting the automaticity of smoking,
      expanding the behavioral repertoire to handle aversive internal states that tend
      to be avoided by smoking, preventing maladaptive beliefs from interfering with
      quitting, taking meaningful action toward change while experiencing ambivalence,
      either replacing the benefits of smoking or accepting their loss, and
      troubleshooting difficulties with nicotine replacement. Findings regarding
      facilitators of quitting supported previous quantitative findings that the ACT
      intervention impacted theory-based targets and highlighted the importance of the
      counseling relationship.

PMID- 29351508
TI  - Gaze Behavior of Gymnastics Judges: Where Do Experienced Judges and Gymnasts Look
      While Judging?
AB  - : Gymnastics judges and former gymnasts have been shown to be quite accurate in
      detecting errors and accurately judging performance. PURPOSE: The purpose of the
      current study was to examine if this superior judging performance is reflected in
      judges' gaze behavior. METHOD: Thirty-five judges were asked to judge 21 gymnasts
      who performed a skill on the vault in a video-based test. Classifying 1 sample on
      2 different criteria, judging performance and gaze behavior were compared between
      judges with a higher license level and judges with a lower license level and
      between judges who were able to perform the skill (specific motor experience
      [SME]) and those who were not. RESULTS: The results revealed better judging
      performance among judges with a higher license level compared with judges with a
      lower license level and more fixations on the gymnast during the whole skill and
      the landing phase, specifically on the head and arms of the gymnast. Specific
      motor experience did not result in any differences in judging performance;
      however, judges with SME showed similar gaze patterns to those of judges with a
      high license level, with 1 difference in their increased focus on the gymnasts'
      feet. CONCLUSION: Superior judging performance seems to be reflected in a
      specific gaze behavior. This gaze behavior appears to partly stem from judges'
      own sensorimotor experiences for this skill and reflects the gymnasts'
      perspective onto the skill.

PMID- 29351509
TI  - Social safety in jeopardy due to gendered masculinity.

PMID- 29351510
TI  - Scapular focused interventions to improve shoulder pain and function in adults
      with subacromial pain: A systematic review and meta-analysis.
AB  - The relationship between subacromial pain syndrome (SAPS) and altered scapular
      movement has been previously reported. The purpose of this review was to
      determine the effect of interventions that focus on addressing scapular
      components to improve shoulder pain, function, shoulder range of motion (ROM),
      and muscle strength in adults with SAPS. Databases searched in September 2016
      were: PubMed, the Cochrane Central Register of Controlled Trials [Central],
      EMBASE [via Ovid] and PEDro. All studies selected for this review were randomized
      controlled trials. In total, six studies met the inclusion criteria and were
      included in the meta-analyses. In adults with SAPS, scapular focused
      interventions significantly improved pain with activities (MD [95% CI] = -0.88 [
      1.19 to -0.58], I2 43%) and shoulder function (-11.31 [-17.20 to -5.41] I2 65%)
      in the short term. No between-group difference in shoulder pain and function were
      found at follow up (4 weeks). A between-group difference in shoulder abduction
      ROM in the short term only was found (12.71 [7.15 to 18.26] degrees , I2 36%). No
      between-group difference in flexion ROM, supraspinatus muscle strength,
      pectoralis minor length or forward shoulder posture were found. In conclusion, in
      adults with SAPS, scapular focused interventions can improve short-term shoulder
      pain and function.

PMID- 29351511
TI  - Chemogenetic Tools for Causal Cellular and Neuronal Biology.
AB  - Chemogenetic technologies enable selective pharmacological control of specific
      cell populations. An increasing number of approaches have been developed that
      modulate different signaling pathways. Selective pharmacological control over G
      protein-coupled receptor signaling, ion channel conductances, protein
      association, protein stability, and small molecule targeting allows modulation of
      cellular processes in distinct cell types. Here, we review these chemogenetic
      technologies and instances of their applications in complex tissues in vivo and
      ex vivo.

PMID- 29351514
TI  - The ACE2/Angiotensin-(1-7)/MAS Axis of the Renin-Angiotensin System: Focus on
      Angiotensin-(1-7).
AB  - The renin-angiotensin system (RAS) is a key player in the control of the
      cardiovascular system and hydroelectrolyte balance, with an influence on organs
      and functions throughout the body. The classical view of this system saw it as a
      sequence of many enzymatic steps that culminate in the production of a single
      biologically active metabolite, the octapeptide angiotensin (ANG) II, by the
      angiotensin converting enzyme (ACE). The past two decades have revealed new
      functions for some of the intermediate products, beyond their roles as substrates
      along the classical route. They may be processed in alternative ways by enzymes
      such as the ACE homolog ACE2. One effect is to establish a second axis through
      ACE2/ANG-(1-7)/MAS, whose end point is the metabolite ANG-(1-7). ACE2 and other
      enzymes can form ANG-(1-7) directly or indirectly from either the decapeptide ANG
      I or from ANG II. In many cases, this second axis appears to counteract or
      modulate the effects of the classical axis. ANG-(1-7) itself acts on the receptor
      MAS to influence a range of mechanisms in the heart, kidney, brain, and other
      tissues. This review highlights the current knowledge about the roles of ANG-(1
      7) in physiology and disease, with particular emphasis on the brain.

PMID- 29351516
TI  - In the Shadow of Giants: Challenges and Opportunities for the New Editor of
      Physiological Reviews.

PMID- 29351515
TI  - Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate
      Disease: Current Knowledge and Emerging Concepts.
AB  - The benefits of exercise on the heart are well recognized, and clinical studies
      have demonstrated that exercise is an intervention that can improve cardiac
      function in heart failure patients. This has led to significant research into
      understanding the key mechanisms responsible for exercise-induced cardiac
      protection. Here, we summarize molecular mechanisms that regulate exercise
      induced cardiac myocyte growth and proliferation. We discuss in detail the
      effects of exercise on other cardiac cells, organelles, and systems that have
      received less or little attention and require further investigation. This
      includes cardiac excitation and contraction, mitochondrial adaptations, cellular
      stress responses to promote survival (heat shock response, ubiquitin-proteasome
      system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein
      response, DNA damage response), extracellular matrix, inflammatory response, and
      organ-to-organ crosstalk. We summarize therapeutic strategies targeting known
      regulators of exercise-induced protection and the challenges translating findings
      from bench to bedside. We conclude that technological advancements that allow for
      in-depth profiling of the genome, transcriptome, proteome and metabolome,
      combined with animal and human studies, provide new opportunities for
      comprehensively defining the signaling and regulatory aspects of cell/organelle
      functions that underpin the protective properties of exercise. This is likely to
      lead to the identification of novel biomarkers and therapeutic targets for heart
      disease.

PMID- 29351517
TI  - Caregiver Difficulties Scale (CDS): Translation and Psychometric Evaluation Among
      Iranian Mothers of Cerebral Palsy Children.
AB  - The aim of this study was to investigate of psychometric properties of the
      Caregiver Difficulties Scale (CDS) for Iranian caregivers of children with
      cerebral palsy (CP). After a forward-backward translation, the Persian version of
      CDS (P-CDS) was administered to 151 Iranian mothers of CP children. The
      confirmatory factor analysis (CFA) was applied to measure the factor structure of
      P-CDS. The reliability was evaluated by examining internal consistency and test
      retest method over a 2-week period using Cronbach's alpha and the intraclass
      correlation coefficient (ICC), respectively. The construct validity was assessed
      by measuring the association between the scores of the P-CDS and Caregiver Burden
      Scale (CBS), World Health Organization Quality of Life (WHOQOL-BREF), the Beck
      Depression Index (BDI II), and the Fatigue Severity Scale (FSS). The fit indices
      showed that the original model of CDS was relatively adequate (chi2/df = 2.03,
      CFI = 0.90, TLI = 0.88 and RMSEA = 0.08). All domains of P-CDS met the minimum
      reliability standards (Cronbach'salpha and ICC > 0.7). All subscales of P-CDS
      were positively correlated with the CBS, BDI-II and FSS and negatively correlated
      with the WHOQOL-BREF. The results showed that P-CDS is a valid and reliable
      measure for assessing the burden of care in Iranian mothers of CP children.

PMID- 29351519
TI  - Websites Related to Volume 32, Issue 1.

PMID- 29351518
TI  - "I'm still dad": The Impact of Scleroderma on being a Father.
AB  - The purpose of this study was to describe the experiences of fathers with
      scleroderma. Ten fathers with scleroderma were interviewed by telephone.
      Interviews were tape-recorded and transcribed verbatim. Two key themes emerged
      related to the emotional impact of the illness and the day to day realities of
      the illness with the unpredictability and rareness of the illness leading to
      ongoing feelings of isolation and fear of mortality. The negative influences of
      being a father with scleroderma included the inability of the fathers to
      participate in physical activities with their children such as outdoor sports and
      throwing balls. Being able to spend quality time with the child was a positive
      influence of the illness.

PMID- 29351521
TI  - Corrigendum.

PMID- 29351520
TI  - Beyond Clinical Complexity: Nonmedical Barriers to Nursing Home Care for Rural
      Residents.
AB  - We conducted a qualitative content analysis of barriers to nursing home admission
      for rural residents. Data came from semi-structured interviews with 23 rural
      hospital discharge planners across five states (Georgia, Idaho, Minnesota,
      Pennsylvania, and Wisconsin). From those, we identified four themes around
      nonmedical barriers to rural nursing home placement with particular salience in
      rural areas: financial issues, transportation, nursing home availability and
      infrastructure, and timeliness. We also identified policy and programmatic
      interventions across four themes: loosen bureaucratic requirements, improve
      communication between facilities, increase rural long-term care capacity, and
      address underlying social determinants of health.

PMID- 29351522
TI  - Evolution of AO Fracture Treatment Part 1: the Internal Fixator.
AB  - Surgical fracture treatment has undergone an extensive evolution in the past
      decades. In the early days achieving solid healing in anatomically reduced
      position was the primary and nearly exclusive goal of fracture treatment. Since
      mainly Lambotte, Danis and Muller in Europe the focus of surgical fracture
      treatment shifted to achieving early recovery of the function of the injured limb
      with safe healing. Considering the shortcomings of the early fracture treatment
      helps understanding the evolution of surgical fracture treatment. The evolution
      of the biomechanical and biological principles of AO plate fixation are discussed
      as a model.

PMID- 29351513
TI  - Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa.
AB  - Because of the compartmentalization of disciplines that shaped the academic
      landscape of biology and biomedical sciences in the past, physiological systems
      have long been studied in isolation from each other. This has particularly been
      the case for the immune system. As a consequence of its ties with pathology and
      microbiology, immunology as a discipline has largely grown independently of
      physiology. Accordingly, it has taken a long time for immunologists to accept the
      concept that the immune system is not self-regulated but functions in close
      association with the nervous system. These associations are present at different
      levels of organization. At the local level, there is clear evidence for the
      production and use of immune factors by the central nervous system and for the
      production and use of neuroendocrine mediators by the immune system. Short-range
      interactions between immune cells and peripheral nerve endings innervating immune
      organs allow the immune system to recruit local neuronal elements for fine tuning
      of the immune response. Reciprocally, immune cells and mediators play a
      regulatory role in the nervous system and participate in the elimination and
      plasticity of synapses during development as well as in synaptic plasticity at
      adulthood. At the whole organism level, long-range interactions between immune
      cells and the central nervous system allow the immune system to engage the rest
      of the body in the fight against infection from pathogenic microorganisms and
      permit the nervous system to regulate immune functioning. Alterations in
      communication pathways between the immune system and the nervous system can
      account for many pathological conditions that were initially attributed to strict
      organ dysfunction. This applies in particular to psychiatric disorders and
      several immune-mediated diseases. This review will show how our understanding of
      this balance between long-range and short-range interactions between the immune
      system and the central nervous system has evolved over time, since the first
      demonstrations of immune influences on brain functions. The necessary
      complementarity of these two modes of communication will then be discussed.
      Finally, a few examples will illustrate how dysfunction in these communication
      pathways results in what was formerly considered in psychiatry and immunology to
      be strict organ pathologies.

PMID- 29351523
TI  - Treatment of Geriatric Proximal Humerus Fractures: Indications and Outcome.
AB  - Treatment algorithms of proximal humerus fractures are still controversially
      discussed. The enthusiasm towards operative treatment after the introduction of
      locking implants, has not been justified by the functional results in the elderly
      population. The majority of those fractures in the geriatric patients can be
      successfully treated conservatively. Thorough clinical and radiological
      examination for fracture analysis, dynamic stability control with the use of an
      image intensifier, and meticulous reduction, in addition with the appropriate
      orthesis for its retention and rehabilitation, are the keys for the successful
      treatment of the proximal humerus fracture in the elderly patient. The present
      review reports on the main treatment aspects of proximal humerus fractures in the
      geriatric population and proposes a treatment algorithm.

PMID- 29351524
TI  - [Results of Surgically Treated Patients for Hip Fracture - Complications,
      Mortality].
AB  - PURPOSE OF THE STUDY Our main objective was to evaluate the mortality and
      complications of patients following surgical treatment of hip fractures and to
      identify the associated risk factors for postoperative mortality. MATERIAL AND
      METHODS We retrospectively reviewed all patients over the age of 50 who underwent
      surgical treatment for femoral neck and peritrochanteric fractures at our
      institution in 2003 and 2013. Mortality was compared between subgroups classified
      by age, gender, fracture type, method of treatment. Correlation between mortality
      and postoperative complications, time to surgery, and blood transfusion need were
      evaluated. Chi-square was used for categorical variables and two-tailed student's
      t-test for continuous variables. Survival curves were compared by the log-rank
      test. Mortality rates were adjusted for patient age and compared to the mortality
      rates of Prague's population in the given years. RESULTS Altogether 425 patients
      were surgically treated for proximal femoral fracture in 2013, while 229 patients
      were treated in 2003. The overall 1-year mortality decreased by 10% over the
      study period (38% in 2003 and 28% in 2013), despite the higher average age in
      2013. Survival was better in all subgroups broken down by diagnosis and method of
      treatment, statistically relevant in the subgroup of femoral neck fractures,
      notwithstanding the method of treatment and in the subgroup treated with total
      hip arthroplasty. The strongest prognostic factor for survival was the advanced
      age. The mortality rate rises significantly over the age of 75. The largest age
      group was between 85-89 years, with 1-year mortality rate of 32%. The annual
      mortality of the general population in Prague aged 85-89 years was 13% and has
      improved only by 1% in the decade. The reoperative rate was 4% and did not affect
      mortality. There was no significant relationship between mortality and
      complications or delay of surgery for up to 4 days. DISCUSSION The factors that
      might have contributed to better survival are the introduction of guidelines for
      hip fracture care to our unit, better prophylaxis of venous thromboembolism,
      improvement of surgical skills due to the growing volume of these cases, and a
      higher rate of discharges to aftercare units. CONCLUSIONS Mortality has
      significantly decreased between 2003 and 2013 (p < 0.001). We didn't find a
      correlation between mortality and delay of surgery up to 4 days. That means that
      a complicated operation such as hip arthroplasty could be postponed and operated
      in more comfortable conditions (in superaseptic OR) by orthopedic surgeons.
      Although we haven't identified any modifiable risk factor, we believe that the
      reasons for better survival are multifactorial as discussed. Key words: hip
      fracture, proximal femoral fracture, mortality, complications, time to surgery.

PMID- 29351525
TI  - Impact of Single Center Treatment on Ewing Sarcoma 10-Year Long Term Survival
      Rates.
AB  - PURPOSE OF THE STUDY Ewing sarcomas (ES) are the second most common solid
      malignant bone tumors in both, children and adolescents, and systemic
      chemotherapy protocols were established during the last 3 decades which proved to
      be a successful approach in addition to local treatment. The purpose of the
      present study is (i) to provide survival rates and prognostic factors for
      patients with ES which received treatment in a single center and (ii) to compare
      data with results of multicenter studies. MATERIALS AND METHODS Patients (n = 38)
      were treated by the same surgeon whereas surgery was combined with radiotherapy
      in 55.3% of the patients (n = 21). Median age at diagnosis was 17.5 years (4.7
      60) and the median follow-up time for all patients was 8.2 years (9.8 years for
      survivors, 3.2 years for non-survivors). RESULTS The survival rate for metastasis
      free sarcoma decreases from 90.5% to 50% for patients diagnosed with disseminated
      disease stage. Patients with a good response to chemotherapy survived in 83.3% of
      the cases. In addition, a higher OS was found for patients younger than 15 years
      (82.4%) when compared to patients older than 15 years (73.3%). In contrast,
      multicenter studies reported lower survival rates for metastasis free (~60%) and
      metastasis stages (< 40%). DISCUSSION The survival rates in the present single
      center study are higher than the rates reported from multi-center studies
      although same chemotherapy protocols were used and no substantially difference
      are apparent for patient population. CONCLUSIONS Based on the present data we re
      emphasize that patients with Ewing sarcoma receive appropriate treatment in a
      large and qualified center particularly considering the survival rates. In
      addition, our data underline that a close collaboration between the oncological
      team and the experienced surgeon is crucial for patient's care. Key words: Ewing
      sarcoma, survival rate, single center, prognostic factors, chemotherapy, surgery,
      multi center, single center.

PMID- 29351526
TI  - Evaluation of the Quality of Life and Psychiatric Symptoms of Patients with
      Primary Coxarthrosis after Total Hip Arthroplasty.
AB  - PURPOSE OF THE STUDY In this study, it was aimed to examine the preoperative and
      postoperative quality of life and psychiatric symptoms of the patients with
      primary coxarthrosis after total hip arthroplasty. MATERIAL AND METHODS 150
      patients undergone total hip arthroplasty were involved in this study. The socio
      demographical data form prepared by the researchers was utilized before and after
      the operation in order to demonstrate disease-related socio-demographical
      characteristics of the patient. The Quality of Life Scale Short Form (SF-36),
      Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Harris Hip Score
      (HHS) and Visual Analog Scale (VSA) were implemented in the preoperative period
      and at 6th and 12th week after the operation. RESULTS Of the patients involved in
      study, 28.7% were male and 71.3% were female. Their mean age was 58.34+/-11.92
      year. While statistically significant differences were found between the
      preoperative and postoperative periods in terms of physical function, physical
      role limitation, emotional role limitation, energy, social function, pain, and
      general health subscales of SF-36, no significant differences were found relating
      mental health subscale. In BAI, BDI, VAS, and HHS comparison, statistically
      significant differences were found between the preoperative and postoperative
      periods, except for BAI. CONCLUSIONS In this study, it was determined that
      primary coxarthrosis affects significantly the quality of the patients' lives in
      a negative way and can be accompanied by mental symptoms. After total hip
      arthroplasty, significant improvement was observed in quality of life, depression
      and pain scores. Key words: total hip prosthesis, quality of life, mental
      symptoms.

PMID- 29351527
TI  - [Treatment of Extensive Chondral Defects of the Patella after Patellar
      Dislocation].
AB  - PURPOSE OF THE STUDY Patellar dislocation is a fairly frequent knee joint injury
      in young patients. In most cases, this injury can be treated conservatively or
      surgically. In many cases, patellar cartilage or lateral femoral condyle or both
      these parts of articular surface are injured, and in conservative treatment this
      chondral damage very often remains undiagnosed. The purpose of this study is to
      evaluate the outcomes of treatment in patients who underwent surgery for patellar
      dislocation and in whom extensive traumatic cartilage lesions of the patella were
      found. MATERIAL AND METHODS The authors carry out a retrospective evaluation of
      outcomes in 34 patients from the period 2005-2014, in whom extensive chondral
      defect of the posterior side of the patella after its traumatic dislocation with
      the mean size of 4.1 cm2 (the maximum size was 28x18 mm) was found, namely in 21
      women and 13 men aged 13-28 years. The patients were indicated for arthroscopic
      surgery based on the clinical examination which revealed a clear traumatic
      patellar dislocation. In 2 radiographs only, an osteochondral fragment was found,
      and in these patients a CT scan of the injured knee was made. The patients were
      retrospectively broken down into 3 sub-groups by the method of treatment of the
      chondral defect. The mean size of the defect in the debridement group was 2.7 cm2
      compared to 4.6 cm2 in the group with cartilage fixation. In group I reinsertion
      through MiniSynthes 2.0 screws (5 patients) was performed, in group II
      reinsertion of the chondral fragment was done using transosseous PDS sutures (19
      patients), in group III debridement of injured cartilage was carried out (10
      patients). RESULTS The patients were assessed postoperatively using Kujala score
      and IKDC score. The mean age of patients at the time of injury was 19.6 years,
      with mean follow-up of 30.2 months. No group reported limitations of range of
      motion at the time of evaluation. Knee pain under load was present in 3 patients
      in group I, in 1 patient in group II and in 7 patients in group III. No patient
      suffered from another patellar dislocation. The mean Kujala score was 84.7 (group
      I), 89.3 (group II), and 78.5 (group III). The IKDC was 84.6 in group I, 87.2 in
      group II, and 74.3 in group III. At the time of evaluation, pre-injury activities
      were resumed by 72% of patients from group I, 82% of patients from group II, and
      69% of patients from group III. DISCUSSION Treatment of primary patellar
      dislocation is still subject to discussions on whether to pursue conservative or
      surgical treatment. The main topic of studies is the subsequent rate of patellar
      re-dislocation and the rate of cartilage damage in patellofemoral joint, examined
      is also the scope of performed surgery, while only very few papers focus on
      treating the injured cartilage of the patella. Despite numerous studies, the
      optimal method of treatment of this injury has been identified as yet.
      CONCLUSIONS Where a serious, extensive fragment of patellar cartilage is found,
      the fixation of cartilage with the use of transosseous PDS sutures brings very
      good and good results, without the necessity of another surgery, while the
      simultaneous treatment of medial patellar retinacula considerably decreases the
      risk of patellar re-dislocation, thus reducing the risk of further damage to
      cartilage of patelofemoral joint. The use of transosseous suture fixation is
      considered by the authors to be more appropriate than the use of screws, mostly
      because no further surgery to remove fixation screws is necessary. Key words:
      acute patellar dislocations, chondral lesions, chondral repair, arthroscopy.

PMID- 29351528
TI  - Cement Augmentation of the Cervical Spine - a Technique Enhancing Stability of
      Anterior Cervical Plating.
AB  - PURPOSE OF THE STUDY The aim of this study is to describe a new technique for
      cement augmentation of primary anterior cervical screw fixation in the sub-axial
      cervical spine. MATERIAL AND METHODS Seven patients underwent anterior cervical
      spine surgery for trauma (two) or tumor infiltration (five) between 2008 and
      2015. The tumor cases underwent corpectomy and anterior plating, with the trauma
      cases undergoing anterior cervical decompression and fusion using iliac crest
      bone graft. All surgeries were performed through the standard anterior approach.
      0.2-0.25 ml of Kyphon cement were introduced into the screw holes before the
      screws were locked into the plate of the anterior construct. Karnofsky Index,
      Spinal Instability Neoplastic score (SINS) were calculated and radiographic
      follow-up performed. RESULTS Median follow-up was 7 months (range 7 weeks-39
      months). There were no complications from cement leakage or construct failure
      during the follow-up period. There were no wound infections or approach-related
      complications. We did not have to re-operate on any patient, cervical spine
      remained stable until the end of follow up. DISCUSSION Until now a limited number
      of papers on cement augmentation of cervical spine mainly dealt with revision
      surgeries, when cement was used as rescue technique to re-establish stability of
      previous fixation or cement augmentation was performed in form of vertebroplasty
      following plate fixation. Our technique intends to prevent revision surgeries and
      to anchor all screws in holes which are evenly filled with bone cement.
      CONCLUSIONS This technique of cement augmentation is a useful adjunct in those
      few patients where a secondary posterior surgery would be high-risk due to the
      general health of the patient, or when life expectancy is limited. We have shown
      that anterior alone reconstruction of the cervical spine with cement augmentation
      of screws did provide sufficient and sufficiently long stability of the cervical
      spine which prevented catastrophic collapse and quadriplegia in patients in poor
      general condition. Key words: cement augmentation, cervical spine, corpectomy,
      tumor, stabilization, fusion.

PMID- 29351529
TI  - [Arthrodesis of the First Metatarsophalangeal Joint by Locking Plate].
AB  - PURPOSE OF THE STUDY The authors in their paper evaluate a group of patients who
      underwent arthrodesis of the first metatarsophalangeal joint using a locking
      plate. MATERIAL AND METHODS In the period 2010-2015, we performed surgery in 51
      patients (56 forefeet), of which in 5 cases bilaterally and in 46 cases
      unilaterally, in 38 women and 13 men. The mean age was 57.8 years, the mean
      follow-up was 3.1 years. The indications for surgery were hallux rigidus in 23
      patients, hallux valgus in 15 patients, hallux varus in 3 patients, and hallux
      erectus in 2 patients. In 4 patients the surgery was performed for valgus
      deformity associated with rheumatoid arthritis, 9 patients were indicated for a
      failure of the prior surgical intervention. In all 56 forefeet, the anatomic, low
      profile titanium plate Variable Angle LCP 1st MTP Fusion Plate 2.4/2.7 was used.
      RESULTS According to Gainor s score the surgical outcomes were assessed as
      excellent in 46 patients who underwent surgery (90%), good in 4 patients (8%),
      fair in 1 patient (2%), and poor in 0 patient (0%). In 53 forefeet, the control
      radiographs showed solid bone union. In 2 patients and 3 forefeet, non-union of
      the arthrodesis occurred. In 2 forefeet, revision arthrodesis was performed,
      after which solid bone union followed. Malpositioned union was reported in 5
      forefeet, of which in 4 cases into valgosity and in 1 case into dorsiflexion.
      DISCUSSION Numerous fixation materials can be used for arthrodesis of the first
      metatarsophalangeal joint. The use of the least stable Kirschner wires (cerclage)
      is being abandoned and substituted with a more stable fixation by screws, memory
      staples and locking plates. The achievement of excellent results requires proper
      positioning of the arthrodesis. Impingement syndrome between the big toe and the
      second toe can result in painful callosities formation, too large dorsiflexion
      can lead to a hallux hammertoe, with reduced big toe support function, to
      metatarsalgia. CONCLUSIONS The arthrodesis is indicated in patients with Grade
      III and IV hallux rigidus, with severe hallux valgus, hallux varus, and in
      patients in whom the previous surgeries failed. We tend to prefer stable
      arthrodesis. Fixation by anatomic LCP plate facilitates early rehabilitation,
      loading and early return to work and sports activities. Key words: arthrodesis,
      metatarsophalangeal joint, hallux rigidus, hallux valgus.

PMID- 29351530
TI  - [Tibio-Calcaneal Arthrodesis with Vertically Placed Tricortical Bone Graft after
      Traumatic Talar Extrusion - a Case Report].
AB  - The aim of this publication is to present a case report of a 38-year-old patient
      with traumatic astragalectomy and resultant foot reconstruction surgery using a
      combination of talus compensation by vertically placed tricortical autograft and
      pantalar arthrodesis with a retrograde calcaneotibial nail (hindfoot nail). The
      advantage of this treatment is based on a solid, stable osteosynthesis, while
      maintaining the length of the limb. Key words: traumatic talar extrusion,
      tibiocalcaneal arthrodesis, hindfoot nail, bone graft, pantalar arthrodesis.

PMID- 29351531
TI  - Flexor Hallucis Longus Transfer for Foot Drop without Functioning Tibialis
      Posterior.
AB  - For a foot drop resulting from peroneal nerve palsy transferring the tibialis
      posterior tendon is a standard surgical treatment. The situation of foot drop
      with no functioning tibialis posterior presents a challenge. We describe a case
      of successful flexor hallucis longus transfer in such a case. Key words: foot
      drop, flexor hallucis longus, peroneal nerve palsy; tendon transfer.

PMID- 29351532
TI  - Proximal Femoral Fractures and Anticoagulation Therapy - When Is Surgery Safe?
AB  - Patients presenting with proximal femur fractures are at high risk of developing
      DVT and pulmonary embolism. Many of these patients suffer from additional
      anticoagulant treatment. Patients on anticoagulation treatment are complex to
      manage, especially regarding timing of surgery due to implemented quality control
      recommendations. The present review analyses the present data timing of surgery
      and perioperative surgical considerations on anticoagulation treatment in this
      patients group.

PMID- 29351533
TI  - Intramedullary Nailing of Metaphyseal Fractures of the Lower Extremity.
AB  - Intramedullary nailing is a worldwide accepted technique for stabilization of
      fractures of long bones. Technique, instruments and implants primarily have been
      developed for the fixation of short (transverse and oblique) diaphyseal
      fractures. First generation nails were hollow and slotted, which gave them some
      elasticity. When the tip of the nail passed the fracture gap, picked up the
      opposite fracture fragment and was driven further down, the longitudinal axis of
      the bone was restored and the extremity realigned. Bone length was restored by
      closure of the fracture gap. The tight connection between the deformable hollow
      nail and the inner cortex at the isthmus realized a press-fit, which achieved a
      very stable bone-implant construct. The nail had the function of a weight
      shearing implant. Interlocked nails represent the second-generation nails. They
      changed the spectrum of indications for nailing considerably. Not only short
      middle-third shaft fractures, but shaft fractures of all types (from transverse
      to comminuted) and all localizations can be stabilized with an interlocked nail.
      Due to interlocking, length and rotation are controlled. The nail bridges the
      area of instability, being a weight-bearing implant. Small diameter, solid nails
      formed the next generation of nail implants. They were conceived for the
      provisional treatment of fractures with an enhanced risk of postoperative
      infection such as open fractures or closed fractures with severe soft tissue
      damage. They were increasingly used for minimal invasive treatment of closed
      fractures without soft tissue damage as well, as reaming was not necessary and
      endosteal blood supply less damaged. Nevertheless, it became clear that they were
      connected with a higher incidence of implant failure and revision surgery.
      Another development was the creation of nails with multiple and angular stable
      interlocking options. Major advantage is that high stability is obtained in the
      fracture fragment, in which multiple interlocking is used. This property gives
      the possibility of nailing fractures close to a joint with a short fracture
      segment (24). Nevertheless, intramedullary nailing of metaphyseal fractures
      remains controversial. Major complications to be avoided are malalignment,
      delayed union, nonunion and implant failure due to suboptimal fracture reduction
      (23).

PMID- 29351534
TI  - Cemented Hemiarthroplasties Are Associated with a Higher Mortality Rate after
      Femoral Neck Fractures in Elderly Patients.
AB  - PURPOSE OF THE STUDY The postoperative outcomes of total hip replacement and
      hemiarthroplasty after femoral neck fractures in elderly patients were analysed
      to determine general and local complications as well as morbidity and mortality
      rates in order to detect risk profiles and assess the best individual treatment
      option. MATERIALS AND METHODS One hundred sixty-one femoral neck fractures among
      patients aged >= 65 years treated with cemented hemiarthroplasty (HA) or
      uncemented total hip arthroplasty (THA) between January 2005 and October 2013
      were evaluated. In the presence of articular pathologies as well as a fracture
      type Garden III or IV, the indication for joint replacement was given. Criteria
      for performing hemiarthroplasty were previously limited mobility. Freely and
      fully mobilised patients and patients with manifested osteoarthritis received a
      cementless THA. A comparison of the observed complications was made,
      differentiating between general and surgery-specific hip-related complications.
      Furthermore, the mortality rates were analysed in relation to the respective
      surgical treatment. RESULTS Seventy cemented HA and ninety-one uncemented THA
      were performed. There was a high complication rate of approximately 19% in both
      surgical intervention groups. The patients were more likely to develop general
      complications (HA 12.8%; THA 10.8%) even though cardiopulmonary complications
      occurred more frequently in the cemented HA group. Four patients died after
      cemented hemiarthroplasty due to thromboembolic events (5.7% mortality rate),
      whereas no deaths occurred after total hip replacement. Surgery-specific
      complications rates were 7.8% in THA and 5.7% in HA patients. CONCLUSIONS THA in
      eldery patients with femoral neck fractures is associated with a higher
      complication rate, mostly of general medical entity. After cemented HA, our study
      reveals a high mortality rate due to thromboembolic events. For patients with
      multimorbidity in particular, these findings therefore suggest that uncemented
      THA should be considered to prevent lethal complications. Key words: femoral neck
      fracture; total hip arthroplasty; hemiarthroplasty; complications.

PMID- 29351535
TI  - [Occurrence and Progression of Early Radiolucent Lines around Total Knee
      Arthroplasty].
AB  - PURPOSE OF THE STUDY Radiolucent (RL) lines may appear around the total knee
      arthroplasty (TKA); they occur much more frequently under the tibial component
      than under the femoral one. The RL lines are gaps between the TKA and the cement,
      or between the cement and the bone bed. They are clearly visible immediately
      after the surgery or may appear later. They constitute pathology of the interface
      and are subject to research mainly due to their potential association with
      aseptic loosening. The aim of this study was to assess how often they are clearly
      visible on the first postoperative radiograph in everyday clinical practice, how
      they develop during the following two years, and to compare the results with the
      available professional literature. Another aim was to assess the relation between
      RL lines and the alignment of components, the patient's habitus and clinical
      outcomes of the surgery. MATERIAL AND METHODS The group included 62 patients with
      a total number of 69 TKA implants, of which 28 were men (45.2%) and 34 women
      (54.8%) aged 46 to 79 years of age. The occurrence of RL lines was monitored on
      the first postoperative radiograph and subsequently at a one-year interval during
      the following 2 years. The location of RL lines and the placement of components
      were assessed radiographically in terms of the concept by Meneghini et al. The
      evaluation of surgical outcomes was done using the Knee Society Score (KSS), and
      the habitus was assessed with the BMI index. Subjective evaluation of the
      surgical outcome was done using the 4-point satisfaction scale. RESULTS The first
      postoperative radiographs showed a RL line at 9 (0.8%) locations in 9 (13.0%)
      TKAs. The control radiographs made 1 year after the surgery showed a RL line at
      42 (3.8%) locations in 29 (42.0%) TKAs. During the last check conducted 2 years
      after the surgery, a RL line was detected at 60 (5.4%) locations in 33 (47.8%)
      TKAs. Throughout the follow-up period, progression of the existing RL line
      occurred at 6 locations in 6 (8.7%) TKAs. On the very contrary, the RL line
      disappeared at 8 locations in 6 (8.7%) TKAs. An association was found between the
      RL line occurrence and postoperative limb axis (a higher risk was posed by the
      varus deformity). Moreover, the frequency of RL lines increased with the growing
      BMI value. No relation was found between the KSS and satisfaction with the
      surgery and the occurrence of RL lines. DISCUSSION AND CONCLUSIONS The occurrence
      of RL lines corresponds roughly with the frequency stated in literature. Some
      lines show progression, other disappear. So far, we have been unable to
      distinguish the predictively significant RL lines from the insignificant ones.
      Important will undoubtedly also be the size of surface of RL lines and their
      cause. More frequent RL lines were observed in the postoperative varus deformity
      of TKA and with the growing BMI value. The RL lines under the anterior part of
      the femoral component showed a tendency to progress. In order to avoid them we
      recommend modifying the cementing technique. Clinically significant is the fact
      that the RL lines occurrence correlates neither with subjective nor with clinical
      outcomes of the surgery. Key words: total knee arthroplasty; total knee
      replacement; radiolucent lines; progression; alignment; Knee Society Score; BMI.

PMID- 29351536
TI  - [Osteochondritis Dissecans in Children - Treated with Arthroscopic Drilling].
AB  - PURPOSE OF STUDY Osteochondritis dissecans (OCHD) is an increasingly diagnosed
      disease among adolescent patients. It is a condition affecting subchondral bone
      and the lining cartilage. If left untreated, it can cause destruction of
      cartilage of the affected joint leading to early development of arthrosis. Mostly
      affected joints are knees and ankles, but affected elbow and other joints have
      been described too. The purpose of our study is to present the patients diagnosed
      and treated surgically at our clinic with arthroscopic drilling in the period
      2010-2015, and subsequently the clinical findings obtained at follow-up checks
      after the surgery. MATERIAL AND METHODS Between 2010 and 2015, a total of 34
      patients (36 joints) underwent surgical treatment at our clinic. Their age ranged
      from 6 to 19 years at the time of surgery, 17 girls and 17 boys underwent the
      surgery. All the patients were treated with transarticular antegrade arthroscopic
      drilling. Each patient was diagnosed based on the clinical finding, radiographs,
      or MRI. The patients were followed after 6 weeks, thereafter 3, 6, and 12 months
      after the surgery. Each patient was evaluated based on the clinical findings
      (presence of swelling, range of motion, and pain according to VAS), and
      radiographs. RESULTS The preoperative VAS was 2.9 and dropped down to 1.5 at the
      first follow-up visit. None of the patients complained of pain at 1-year follow
      up. 34 (out of 36) patients suffered joint swelling preoperatively, 6 weeks after
      the surgery only 9 patients presented with ongoing swelling, at 1-year follow-up
      no patient reported this problem. The X-ray findings showed regression in 35 of
      36 patients one year after the surgery. One female patient underwent redo surgery
      because of an ongoing restriction of movement and X-ray finding persistence.
      DISCUSSION Majority of patients with OCHD can be treated conservatively. Physical
      activity modification and temporary immobilization are commonly used treatment
      methods of this condition. If conservative treatment is unsuccessful, arthroscopy
      should be considered. Stable lesions have a high chance of spontaneous healing
      without surgery. There is a variety of arthroscopic treatment methods. Mostly
      transarticular transchondral drilling is used to treat this condition. CONCLUSION
      Treatment of OCHD with arthroscopic drilling shows promising results in our
      cohort of patients. We recommend to use arthroscopic drilling in patients in
      stage I to III according to X-ray when 3 months of conservative treatment do not
      improve the clinical symptoms, swelling and restriction of movement. Antegrade
      drilling is the most frequently used treatment method in OCHD at our clinic, we
      consider this technique a simple and effective, with short surgical time needed.
      Key words: osteochondritis dissecans, treatment, arthroscopy, drilling.

PMID- 29351537
TI  - [Influence of Enhanced Recovery Regime on Early Outcomes of Total Knee
      Arthroplasty].
AB  - PURPOSE OF THE STUDY Our study compared early outcomes of total knee arthroplasty
      performed in conventional and enhanced perioperative care regimes, i.e. without
      the use of Redon drain, with intensified perioperative analgesia and more
      frequent and intensive rehabilitation regime in the latter. MATERIAL AND METHODS
      The prospective study included 194 patients (76 men and 118 women) implanted with
      primary knee endoprosthesis. The mean age was 68.8 (44.7 - 88.0 years). The
      patients were divided into two groups - the "enhanced" and "conventional"
      procedures. In the first group, Redon suction drain was not inserted at the end
      of the surgery, and the patients commenced passive knee mobility exercise of the
      operated knee immediately after being brought back from the operating theatre.
      The general anaesthesia was supplemented by a combined femoral nerve block and
      wound infiltration with local anaesthetics. The second group comprised the
      patients who underwent conventional surgery, i.e. with the use of drain, without
      femoral nerve block, with no wound infiltration with local anaesthetics, and
      without immediate post-operative mobilization of the joint. The evaluation was
      carried out using regular clinical tools (subjective evaluation, objective
      examination, questionnaire and Knee Society Score (KSS)). Standard statistical
      methods were applied to data processing. RESULTS The patients under the
      "conventional regime" showed a significantly sharper drop in haemoglobin and
      haematocrit levels, higher consumption of blood transfusion and analgesics during
      the first three days after the surgery. The patients under the "enhanced regime"
      showed a better range of joint motion at hospital discharge, flexion in
      particular (p = 0.001). During the hospital stay no frequent swelling, secretion
      or wound reddening was reported in any of the monitored groups. In the
      "conventional" group, however, haematomas were more frequently present. The
      postoperative checks did not reveal any differences in satisfaction of the
      patients with the surgery. At the first follow-up examination at the outpatient
      department the "conventional" group patients more often reported knee pain and a
      feeling of a swollen knee. Nonetheless, their statements did not correspond with
      the VAS score. In the period between the 6th and 12th months following the
      surgery, the differences in the range of motion disappeared. The KSS showed a
      noticeable improvement in both the groups as against the preoperative values. In
      the "enhanced" group patients, the score increased dramatically at the beginning,
      whereas in the "conventional" group, the score was growing slowly and gradually
      until the last follow-up check after the surgery. The "conventional" group
      patients more frequently reported infectious complications (surface and deep
      wound infections: 4 vs. 2 patients) requiring a revision surgery (p = 0.024).
      DISCUSSION Recently, attention has been drawn to the rapid recovery approach,
      which eliminated postoperative immobilization and enabled the patient to start
      exercising already on the day of the surgery, with some patients even walking
      independently. The individual enhanced recovery regimes differ in details but
      mostly result in achieving the aim much sooner when compared to the conventional
      approaches. The patients under the enhanced recovery regimes can accomplish
      better functional outcomes in the first few months after the surgery than the
      patients undergoing the surgery under the conventional regime. The routine use of
      Redon drains in TKA is obviously unnecessary; it tends to be associated with a
      higher blood loss and a higher risk of prosthetic joint infection. CONCLUSIONS
      The TKA implant without suction drains combined with intensified perioperative
      analgesia and intensive postoperative rehabilitation is a safe way to earlier
      recovery of the function of the operated knee, or, by extension, the lower limb.
      The described approach is not associated with a higher risk of perioperative
      complications (bleeding, healing disorders or early infections). Patients also
      benefit from lower blood losses. Based on the results of our study, we recommend
      performing the TKA surgeries routinely without drains, with perioperative
      analgesia and immediate postoperative joint mobilization. Key words: total knee
      arthroplasty; perioperative care; rapid recovery; drainage; active movement;
      postoperative outcomes; pain; infection.

PMID- 29351538
TI  - [Bacteriuria and Symptomatic Urinary Tract Infections during Antimicrobial
      Prophylaxis in Patients with Short-Term Urinary Catheters - Prospective
      Randomised Study in Patients after Joint Replacement Surgery].
AB  - PURPOSE OF THE STUDY A very serious complication following joint replacement
      surgery is periprosthetic joint infection that can be caused by a urinary tract
      infection. Insertion of an indwelling urinary catheter constitutes a risk factor
      that may result in urinary tract infections. The aim of this prospective
      randomised study was to compare the occurrence of significant bacteriuria and
      symptomatic urinary tract infections during antibiotic prophylaxis at the time of
      removal of an indwelling urinary catheter by cotrimoxazole in two doses and with
      no administration of antibiotics. We also monitored the incidence of potential
      periprosthetic infection following the endoprosthesis implantation. The findings
      of preoperative urine tests were compared with the declared negative preoperative
      examination. MATERIAL AND METHODS The study included patients indicated for a
      total hip or knee replacement with a negative urine culture as a part of the
      preoperative testing. Where leukocyteria was detected, urine culture by mid
      stream clean catch urine was obtained. The second part included patients, in whom
      an indwelling urinary catheter had to be inserted postoperatively for urine
      retention and/or monitoring of fluid balance and who were divided into two groups
      on a rota basis. No antibiotics were administered to the first group, whereas
      Cotrimoxazol 960 mg tablets p.o. was administered to the second group, 14 and 2
      hours before the removal of the catheter. The urine culture test was performed 4
      hours after the removal of the indwelling urinary catheter, in both the groups.
      The test was repeated after 14 days and a questionnaire was filled in to report
      urinary tract complications. Considered as significant bacteriuria by urinalysis
      was the laboratory finding of > 10x4 CFU/ml in case of a single pathogen or >
      10x5 in case of multiple pathogens. The results were statistically processed by
      Fischer's exact test with the level of significance = 0.05. RESULTS In the first
      part of the study leukocyturia was detected by a test strip in 112 of the total
      of 478 patients. In 10 women, significant bacteriuria was found. Altogether 50
      women and 50 men were randomly assigned to the second part of the study. The
      indwelling urinary catheter was in place for 4 days on average. In men, no
      statistically significant difference was detected in significant bacteriuria
      findings, in women a statistically significant difference of p = 0.00162 was
      found after the removal and after 14 days the borderline of statistical
      significance of p = 0.0507 was achieved, but no symptomatic urinary tract
      infection was present. In the period from 20 to 32 months following the total
      joint replacement, no periprosthetic infection caused by urinary tract infection
      was reported. DISCUSSION There is enough evidence to prove the correlation
      between the symptomatic urinary tract infection and periprosthetic infection. On
      the other hand, asymptomatic bacteriuria is a common finding in patients before
      the planned hip of knee joint replacement and its treatment is not recommended.
      No consensus has been achieved as yet regarding the method of antibiotic
      prophylaxis for an inserted urinary catheter. Antibiotics are administered
      throughout the period of catheterisation by an indwelling urinary catheter,
      during its removal, or are not administered at all. In our study antibiotics were
      administered during the removal of an indwelling urinary catheter and a
      statistically significant difference was found in women. It concerned, however,
      only a higher incidence of asymptomatic bacteriuria not treated by antibiotics,
      which in the next follow-up period did not lead to periprosthetic infection.
      CONCLUSIONS Despite the negative pre-operative urine culture, frequent incidence
      of leukocyturia and symptomatic urinary infections were detected in a fairly high
      number of cases. Therefore, we recommend asking the patients during the hospital
      admission process specifically about the urinary infection symptoms. The results
      of our study show that antibiotic prophylaxis during the removal of indwelling
      urinary catheters placed for a short-term is unnecessary. Key words:
      endoprosthesis, urinary catheter, bacteriuria, urinary tract infection.

PMID- 29351539
TI  - [Correlation between the Arthroscopic and MRI Findings in Patients Active in
      Sports with Clinically Suspected Acetabular Labral Tear - Prospective Study
      Results].
AB  - PURPOSE OF THE STUDY The aim of our prospective study was to establish
      correlation between the arthro-MRI and arthroscopic findings in patients active
      in sports clinically suspected of having a hip labral tear. We sought to identify
      the benefits of arthro-MRI for clinical practice prior to the considered hip
      arthroscopy. MATERIAL AND METHODS The prospective study included 34 patients with
      hip pain and clinically suspected of having a labral tear. The group consisted of
      19 men (55.9%) and 15 women (44.1%) of the mean age of 32.2 years (18 to 50
      years). All our patients were active athletes, either professional (12; 35.3%) or
      recreational (22; 64.7%). Included in the study were exclusively patients aged 18
      50 with hip pain lasting longer than 3 months, not responding to conservative
      therapy, with normal X-ray findings, or FAI syndrome. The patients underwent
      arthro-MRI and subsequently also hip arthroscopy, namely within no more than 3
      months. The description of findings was translated into simple numerical scales,
      assessed using Spearman s rank correlation coefficient. We also examined the
      specificity, sensitivity, positive and negative predictive values and the odds
      ratio at various cut-off values of the scale for arthro-MRI. The statistical
      significance was set at the alpha level = 5%. The quality of tests was also
      evaluated using the ROC curve. RESULTS In hips assessed by the radiologist as
      reliably with no pathological finding (MRI type 1) the negative predictive value
      achieves 83.3% and the positive predictive value of 85.7%, with 96.0% sensitivity
      and 55.6% specificity. When evaluating the reliably negative finding together
      with the likely negative finding (MRI type 2) as against the pathological and
      certainly pathological findings (MRI type 3 and 4), the negative predictive value
      is 57.1%, the positive predictive value 95.0%, the specificity 88.9% and the
      sensitivity 76.0%. DISCUSSION In our study, the values achieved were comparable
      to or better than those reported by foreign authors in their studies establishing
      correlations between the arthro-MRI and intraoperative findings. Significantly
      higher was primarily the negative predictive value. CONCLUSIONS The results of
      our study indicate that the arthro-MRI performed as a part of preoperative
      examination prior to hip arthroscopy has adequate specificity and sensitivity in
      patients with suspected labral tear. Based on this examination a decision can be
      made as to whether to perform arthroscopy. Our study also shows that it is
      essential to have a highly competent radiologist to evaluate the arthro-MRI
      results. Key words: hip arthroscopy, labral tears, arthro-MRI, hip joint,
      predictive value of tests, sensitivity and specificity, minimally invasive
      surgical procedures/methods.

PMID- 29351540
TI  - [Our Experience with the Total Replacement of the First Metatarsophalangeal Joint
      by Medin PH-flex].
AB  - PURPOSE OF THE STUDY: The first metatarsophalangeal (MTP) joint replacement ranks
      among the treatment methods of patients with hallux rigidus. The paper aims to
      evaluate the short-term to mid-term outcomes and to present clinical experience
      with our Medin PH-flex implant. MATERIAL AND METHODS In the period from January
      2011 to 2016 we performed total replacement of the first MTP joint in 31
      patients, in 4 cases bilaterally. In total, 35 implants were evaluated. The mean
      age of the patient at the time of surgery was 57.7 years (39-72 years). The
      surgery was conducted in 29 women and 2 men. The patients were evaluated using
      the AOFAS score (American Orthopaedic Foot and Ankle Society score), the
      radiographs were assessed as to the potential occurrence of radiolucent lines,
      with major stress put on the assessment of the mobility in MTP joint and its
      position. The pain was assessed based on the VAS score. RESULTS Prior to the
      joint replacement surgery, the mean AOFAS score in patients was 55.6 (35-65).
      Postoperatively, the mean AOFAS score was 80.8 (65-95). The pain suffered by
      patients was evaluated with the use of the Pain Visual Analogue Scale (VAS
      score). The preoperative mean VAS score was 5 (2-8), whereas the postoperative
      score improved to mean VAS 2 (0-4). The range of motion was clinically assessed
      with a goniometer. The mean range of motion of plantar flexion and dorsiflexion
      was 16.00 degrees  (5-35 degrees ) and 28.60 degrees  (10-55 degrees ),
      respectively. The mean range of motion was 36 degrees  (15-60 degrees ). No
      intraoperative complications were observed. In all the patients, the surgical
      wound healed per primam. In 2 female - (5.7 %) of the whole group of patients who
      underwent surgery a deep infection occurred, namely 10 and 21 months following
      the implantation. In both the female patients their condition was managed by
      joint revision operation and by a simple removal of the implant. DISCUSSION Joint
      replacement related matters were repeatedly discussed in professional literature.
      There are many papers published in the literature on this topic. A whole range of
      the first MTP joint implants of different shapes have been developed, with
      extremely different clinical results. CONCLUSIONS An appropriately chosen type of
      the implant, a fitting indication and a correctly applied implantation technique
      can lead to the desired good outcome. The first MTP joint replacement should be
      indicated after careful consideration since the management of a potential joint
      replacement failure can often be very technically challenging and quite
      mutilating for the patient. The mid-term outcomes of the Medin a.s. first MTP
      implant seem to be promising. It will, however, be necessary to wait for long
      term outcomes in order to evaluate the final benefits of this type of implant in
      patients with hallux rigidus. Key words: hallux rigidus, arthroplasty of the MTP
      joint, hemiarthroplasty, silicone implant.

PMID- 29351541
TI  - Middle Term Results of Simple Open Hip Reduction of Irreducible DDH - What Is the
      Cut-off Age to Safely Perform It with Lower Complications?
AB  - PURPOSE OF THE STUDY When developmental dysplasia of the hip (DDH) is irreducible
      by conservative means, then surgical open hip reduction is the choice. When done
      before walking age simple open hip reduction (SOHR) is most often enough to
      stabilize the hip. We tested the hypothesis that simple open hip reduction gives
      enough stability even in severe Tonnis 4 grades of dislocation. We tried to find
      what is the cut-off age to safely perform SOHR with lower complications. MATERIAL
      AND METHODS From 193 open hip reductions (OHR) of irreducible DDH in 123 children
      for the period 1995-2010 year with X-ray follow up of at least 8 years and full
      documentation we investigated 75 SOHR. Mean age at follow-up was 13 years and 5
      months for the whole group and 8 years and 3 months for the SOHR patients. Age at
      operation - 7 months to 7.5 years for all patients with OHR, with average OR age
      for SOHR - 18 months. The traditional surgical technique of open hip reduction
      was performed through lateral Murphy's approach but with sparing the attachment
      of the piriformis muscle with the underlying blood supply to the epiphysis during
      circumferential capsulotomy. We used McKay clinical criteria, radiological
      classifications of Tonnis, Severin, Herring-Mose and Kalamchi & MacEwen. RESULTS
      When analyzing the results, there came up a strong statistical correlation
      between bilaterality and Tonnis grade 4. The final CE angle of Wiberg was on
      average 28o. According to Severin classification: 74% were excellent and 10% good
      or 84 % successful results. But according to Herring-Mose sphericity scoring -
      60% were good and 30% fair. Mose's fair is a potential cam-type femoro-acetabular
      impingement (FAI). Clinically according to McKay criteria - 10% excellent and 54%
      good, or 64% of the operated hips were clinically acceptable, which correlates
      more with the radiological results according to Mose than with Severin. Avascular
      necrosis (AVN) of the femoral head (FH) according to Kalamchi was: Type I - 6%,
      Type II - 12 %, Type III - 0%, Type IV - 8 %. Types II and IV represent 20 % of
      the operated hips. The presence of ossific nucleus in the femoral epiphysis on
      initial X-ray didn't have a statistical impact on AVN frequency. When analyzing
      the impact of severity of dislocation and trying to find the cut-off age for
      fewer complications, there came up a strong statistical significance between AVN
      IV type appearance in Tonnis grade 4 hips when age at operation was above 9
      months. CONCLUSIONS The thorough capsuloplasty after FH reduction in the
      acetabular socket is enough for stability even in Tonnis 4. When OR age is below
      9 months severe AVN is lower and Herring-Mose FH sphericity scoring is higher.
      Key words: DDH, simple open hip reduction, avascular necrosis of femoral head.

PMID- 29351542
TI  - Carpal Tunnel Syndrome Surgery Anti-Adhesion Gel Is Effective?
AB  - PURPOSE OF THE STUDY The purpose of the current study is to assess the efficacy
      of anti-adhesion gel on the symptom severity and functional outcomes after mini
      incision open surgery for carpal tunnel syndrom (CTS). MATERIAL AND METHODS A
      total of 200 CTS patients (154 women, 46 men) were included in this study. Group
      I (n = 100; 78 women, 22 men) did not receive local administration of anti
      adhesion gel, while anti-adhesion gel consisting of hyaluronic acid
      carboxymethylcellulose (Seprafilm(r), SanofiBiosurgery, Bridgewater, NJ, USA) was
      locally applied to patients in Group II (n = 100; 76 women, 24 men). All patients
      recruited in this study had received conservative treatment comprised of non
      steroidal antiinflammatory drugs, steroid injection, replacement of vitamin B and
      stabilization with splints. Cases that did not benefit from these therapeutic
      options during one year were assigned as candidates for surgical treatment.
      RESULTS There was no significant difference between two groups in terms of mean
      age, gender distribution, preoperative and postoperative Boston questionnaire
      (BQ) scores, difference of BQ scores after the operation, and the presence of the
      disease on the left or right side. According to postoperative 1. Year results,
      there was no significant difference between two groups. CONCLUSIONS Results of
      the current study demonstrated that use of anti-adhesion gel during mini incision
      open surgery for CTS did not bring about significant advantages in terms of
      functional or symptomatic outcomes. Further, controlled trials on larger series
      are warranted to understand the beneficial effects of anti-adhesive materials
      during the surgical treatment of CTS. Key words: anti-adhesion gel, Boston
      questionnaire, carpal tunnel syndrome.

PMID- 29351543
TI  - [Severe Lower Extremity Infections Treated with Hip Disarticulation - Case
      Series].
AB  - Hip disarticulation is a major ablative procedure with serious risks as well as
      consequences for the patient, performed rarely for a lower extremity infection.
      According to literature, the mortality rate in these procedures reaches up to
      60%. Unfavourable prognostic factors are emergency surgeries without adequate
      preparation of the patient and surgeries indicated for an ischemic terrain
      infection. The authors present four cases of hip disarticulation for severe lower
      extremity infection. In one patient, the procedure was performed urgently for
      necrotising fasciitis in the lower extremity extending up to the groin area, in
      the other three patients for non-healing femoral stump infection following the
      lower extremity amputation for vascular causes, of which two cases got
      complicated by the presence of TKA. Two of the patients treated surgically for
      stump infection died two months after the surgery due to respiratory
      complications. The two surviving patients underwent the last check one year
      following the surgery, they are both capable of independent locomotion with two
      underarm crutches and use the prosthesis only rarely. In the discussion, the
      factors influencing the mortality rate of the procedure, the principles of
      surgical and antimicrobial therapy, and the use of the negative-pressure wound
      therapy are analysed. The underlying principles of the care for patients with
      severe infections of the musculoskeletal system are infection focus debridement
      with the removal of foreign material, antibiotic (anti-infective) therapy
      targeted based on the cultivation results, wound management aimed to prevent
      contamination with nosocomial strains, and multidisciplinary cooperation -
      orthopaedist/surgeon, infectious disease physician, intensive care specialist,
      nutrition and rehabilitation specialist, nursing and prosthetic care providers.
      Key words: hip disarticulation, infection, necrotizing fasciitis.

PMID- 29351544
TI  - Long-Term Exposure to Fine Particulate Matter, Blood Pressure, and Incident
      Hypertension in Taiwanese Adults.
AB  - BACKGROUND: Long-term exposure to particulate matter (PM) air pollution may
      increase blood pressure and the risk of hypertension. However, epidemiological
      evidence is scarce and inconsistent. OBJECTIVES: We investigated the associations
      between long-term exposure to PM with an aerodynamic diameter <2.5MUm (PM2.5),
      blood pressure, and incident hypertension in a large Taiwanese cohort. METHODS:
      We studied 361,560 adults >=18y old from a large cohort who participated in a
      standard medical examination program during 2001 to 2014. Among this group,
      125,913 nonhypertensive participants were followed up. A satellite-based
      spatiotemporal model was used to estimate the 2-y average PM2.5 concentrations at
      each participant's address. Multivariable linear regression was used in the cross
      sectional data analysis with the 361,560 participants to investigate the
      associations between PM2.5 and systolic blood pressure (SBP), diastolic blood
      pressure (DBP), and pulse pressure (PP), and Cox proportional hazard regression
      was used in the cohort data analysis with the 125,913 participants to investigate
      the associations between PM2.5 and incident hypertension. RESULTS: Each 10-MUg/m3
      increment in the 2-y average PM2.5 concentration was associated with increases of
      0.45 mmHg [95% confidence interval (CI): 0.40, 0.50], 0.07 mmHg (95% CI: 0.04,
      0.11), and 0.38 mmHg (95% CI: 0.33, 0.42) in SBP, DBP, and PP, respectively,
      after adjusting for a wide range of covariates and possible confounders. Each 10
      MUg/m3 increment in the 2-y average PM2.5 concentration was associated with an
      increase of 3% in the risk of developing hypertension [hazard ratio=1.03 (95% CI:
      1.01, 1.05)]. Stratified and sensitivity analyses yielded similar results.
      CONCLUSIONS: Long-term exposure to PM2.5 air pollution is associated with higher
      blood pressure and an increased risk of hypertension. These findings reinforce
      the importance of air pollution mitigation strategies to reduce the risk of
      cardiovascular disease. https://doi.org/10.1289/EHP2466.

PMID- 29351545
TI  - Love Song Blues: DEHP Alters Courtship Vocalizations in Mice.

PMID- 29351546
TI  - Accessing an Expanded Exposure Science Module at the Comparative Toxicogenomics
      Database.
AB  - SUMMARY: The Comparative Toxicogenomics Database (CTD; http://ctdbase.org) is a
      free resource that provides manually curated information on chemical, gene,
      phenotype, and disease relationships to advance understanding of the effect of
      environmental exposures on human health. Four core content areas are
      independently curated: chemical-gene interactions, chemical-disease and gene
      disease associations, chemical-phenotype interactions, and environmental exposure
      data (e.g., effects of chemical stressors on humans). Since releasing exposure
      data in 2015, we have vastly increased our coverage of chemicals and
      disease/phenotype outcomes; greatly expanded access to exposure content; added
      search capability by stressors, cohorts, population demographics, and measured
      outcomes; and created user-specified displays of content. These enhancements aim
      to facilitate human studies by allowing comparisons among experimental parameters
      and across studies involving specified chemicals, populations, or outcomes.
      Integration of data among CTD's four content areas and external data sets, such
      as Gene Ontology annotations and pathway information, links exposure data with
      over 1.8 million chemical-gene, chemical-disease and gene-disease interactions.
      Our analysis tools reveal direct and inferred relationships among the data and
      provide opportunities to generate predictive connections between environmental
      exposures and population-level health outcomes. https://doi.org/10.1289/EHP2873.

PMID- 29351547
TI  - Mortality and continuity of care - Definitions matter! A cohort study in
      diabetics.
AB  - OBJECTIVE: To demonstrate that when investigating the relevance of continuity of
      care for patient outcomes, different definitions can lead to contradicting
      results. METHODS: We used claims data from the regional public health insurer of
      Lower Austria covering the period from 2008 to 2011. The study sample included
      subjects with repeated dispensings of anti-diabetic drugs. The continuity of care
      index was calculated firstly based on a patient's contacts with general
      practitioners (primary COCI) and secondly based on contacts at all medical
      disciplines (total COCI). The association of the two continuity of care measures
      with mortality was assessed in separate univariable and multivariable Cox
      regression models. RESULTS: Our study sample consisted of 51,717 patients with a
      median observation time of 3.65 years. The data showed that a high total COCI was
      associated with increased mortality, while there was no association between
      primary COCI and mortality. CONCLUSIONS: Measures of continuity of care are
      highly sensitive to the type of medical disciplines taken into account. The
      continuity of care index calculated from contacts at all medical disciplines
      might measure diversity rather than continuity of care.

PMID- 29351548
TI  - Common cuckoos (Cuculus canorus) affect the bacterial diversity of the eggshells
      of their great reed warbler (Acrocephalus arundinaceus) hosts.
AB  - The common cuckoo (Cuculus canorus) is an avian brood parasite, laying its eggs
      in the nests of other bird species, where these hosts incubate the parasitic
      eggs, feed and rear the nestlings. The appearance of a cuckoo egg in a host nest
      may change the bacterial community in the nest. This may have consequences on the
      hatchability of host eggs, even when hosts reject the parasitic egg, typically
      within six days after parasitism. The present study revealed the bacterial
      community of cuckoo eggshells and those of the great reed warbler (Acrocephalus
      arundinaceus), one of the main hosts of cuckoos. We compared host eggs from non
      parasitized clutches, as well as host and cuckoo eggs from parasitized clutches.
      As incubation may change bacterial assemblages on eggshells, we compared these
      egg types in two stages: the egg-laying stage, when incubation has not been
      started, and the mid-incubation stage (ca. on days 5-7 in incubation), where heat
      from the incubating female dries eggshells. Our results obtained by the 16S rRNA
      gene sequencing technique showed that fresh host and cuckoo eggs had partially
      different bacterial communities, but they became more similar during incubation
      in parasitized nests. Cluster analysis revealed that fresh cuckoo eggs and
      incubated host eggs in unparasitized nests (where no cuckoo effect could have
      happened) were the most dissimilar from the other groups of eggs. Cuckoo eggs did
      not reduce the hatchability of great reed warbler eggs. Our results on the cuckoo
      great reed warbler relationship supported the idea that brood parasites may
      change bacterial microbiota in the host nest. Further studies should reveal how
      bacterial communities of cuckoo eggshells may vary by host-specific races
      (gentes) of cuckoos.

PMID- 29351549
TI  - Weeds and ground-dwelling predators' response to two different weed management
      systems in glyphosate-tolerant cotton: A farm-scale study.
AB  - The use of glyphosate, as a post-emergence broad-spectrum herbicide in
      genetically modified glyphosate-tolerant (GT) cotton, supposes a big change in
      weed management programs with respect to a conventional regime. Thus, alterations
      in arable flora and arthropod fauna must be considered when evaluating their
      potential impacts. A 3-year farm-scale study was conducted in a 2-ha GT cotton
      crop, in southern Spain, to compare the effects of conventional and glyphosate
      herbicide regimes on weed abundance and diversity and their consequences for
      ground-dwelling predators. Surveys reveal that weed density was relatively low
      within all treatments with a few dominant species, with significantly higher weed
      densities and modifications of the floristic composition in glyphosate-treated
      plots that led to an increase in the abundance of Portulaca oleracea and to a
      reduction in plant diversity. The activity-density of the main predatory
      arthropod taxa (spiders, ground beetles, rove beetles and earwigs) varied among
      years, but no significant differences were obtained between conventional and
      glyphosate herbicide regimes. However, significant differences between treatments
      were obtained for ground beetles species richness and diversity, being higher
      under the glyphosate herbicide regime, and a positive correlation with weed
      density could be established for both parameters. The implications of these
      findings to weed control in GT cotton are discussed.

PMID- 29351551
TI  - Periodontal health status and lung function in two Norwegian cohorts.
AB  - RATIONALE AND OBJECTIVES: The oral cavity is united with the airways, and thus
      poor oral health may affect respiratory health. However, data on the interaction
      of periodontal and respiratory health is limited. We aimed to evaluate whether
      periodontal health status, assessed by the Community Periodontal Index (CPI), was
      related to lung function among young and middle-aged adults in two Norwegian
      cohorts. METHODS: Periodontal health status and lung function were measured among
      656 participants in the Norwegian part of the European Community Respiratory
      Health Survey (ECHRS III) and the RHINESSA offspring study. Each participant was
      given a CPI-index from 0 to 4 where higher values reflect poorer periodontal
      status. The association between CPI and lung function was estimated with linear
      regression adjusting for age, gender, smoking, body mass index, exercise,
      education, use of antibiotics, inhaled medication and corrected for clustering
      within families. MAIN RESULTS: Participants with CPI 3-4 had significantly lower
      FEV1/FVC ratio compared to participants with CPI 0, b (95% CI) = -0.032 (-0.055, 
      0.009). Poorer periodontal health was associated with a significant decrease in
      the FEV1/FVC ratio with an adjusted regression coefficient for linear trend b
      (95% CI) = -0.009 (-0.015, -0.004) per unit increase in CPI. This negative
      association remained when excluding asthmatics and smokers (-0.014 (-0.022, 
      0,006)). CONCLUSIONS: Poorer periodontal health was associated with increasing
      airways obstruction in a relatively young, healthy population. The oral cavity is
      united with the airways and our findings indicate an opportunity to influence
      respiratory health by improving oral health.

PMID- 29351550
TI  - Differential actions of PPAR-alpha and PPAR-beta/delta on beige adipocyte
      formation: A study in the subcutaneous white adipose tissue of obese male mice.
AB  - BACKGROUND AND AIMS: Obesity compromises adipocyte physiology. PPARs are
      essential to adipocyte plasticity, but its isolated role in the browning
      phenomenon is not clear. This study aimed to examine whether activation of PPAR
      alpha or PPAR-beta/delta could induce beige cell depots in the subcutaneous white
      adipose tissue of diet-induced obese mice. MATERIAL AND METHODS: Sixty animals
      were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat
      diet (HF, 50% lipids) for ten weeks. Then each group was re-divided to begin the
      treatments that lasted 4 weeks, totalizing six groups: C, C-alpha (C plus PPAR
      alpha agonist, 2.5 mg/kg BM), C-beta (C plus PPAR-beta/delta agonist, 1 mg/kg
      BM), HF, HF-alpha (HF plus PPAR-alpha agonist), HF-beta (HF plus PPAR-beta/delta
      agonist). RESULTS: HF animals presented with overweight, glucose intolerance and
      subcutaneous white adipocyte hypertrophy. Both treatments significantly
      attenuated these parameters. Browning, verified by UCP1 positive beige cells and
      enhanced body temperature, was just observed in PPAR-alpha treated groups. PPAR
      alpha agonism also elicited an enhanced gene expression of the thermogenesis
      effector UCP1, the beige-selective gene TMEM26 and the PRDM16, an essential gene
      for brown-like phenotype maintenance in the beige adipocytes when compared to
      their counterparts. The enhanced CIDEA and the reduced UCP1 gene levels might
      justify the white phenotype predominance after the treatment with the PPAR
      beta/delta agonist. CONCLUSIONS: This work provides evidence that the PPAR
      beta/delta agonist ameliorated metabolic disorders through enhanced beta
      oxidation and better tolerance to glucose, whereas the PPAR-alpha agonism was
      confirmed as a promising therapeutic target for treating metabolic diseases via
      beige cell induction and enhanced thermogenesis.

PMID- 29351552
TI  - In-situ recording of ionic currents in projection neurons and Kenyon cells in the
      olfactory pathway of the honeybee.
AB  - The honeybee olfactory pathway comprises an intriguing pattern of convergence and
      divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information
      on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this
      information reliably, PNs employ relatively high spiking frequencies with complex
      patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB).
      This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l
      ALT). PNs from both tracts transmit information from a wide range of similar
      odors, but with distinct differences in coding properties. In the MBs, PNs form
      synapses with many Kenyon cells (KC) that encode odors in a spatially and
      temporally sparse way. The transformation from complex information coding to
      sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic
      neuronal properties as well as GABAergic inhibition are thought to contribute to
      this change in odor representation. In the present study, we identified intrinsic
      neuronal properties promoting coding differences between PNs and KCs using in
      situ patch-clamp recordings in the intact brain. We found very prominent K+
      currents in KCs clearly differing from the PN currents. This suggests that odor
      coding differences between PNs and KCs may be caused by differences in their
      specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs
      did not reveal any differences at a qualitative level.

PMID- 29351553
TI  - Hierarchical and hybrid energy storage devices in data centers: Architecture,
      control and provisioning.
AB  - Recently, a new approach has been introduced that leverages and over-provisions
      energy storage devices (ESDs) in data centers for performing power capping and
      facilitating capex/opex reductions, without performance overhead. To fully
      realize the potential benefits of the hierarchical ESD structure, we propose a
      comprehensive design, control, and provisioning framework including (i) designing
      power delivery architecture supporting hierarchical ESD structure and hybrid ESDs
      for some levels, as well as (ii) control and provisioning of the hierarchical ESD
      structure including run-time ESD charging/discharging control and design-time
      determination of ESD types, homogeneous/hybrid options, ESD provisioning at each
      level. Experiments have been conducted using real Google data center workloads
      based on realistic data center specifications.

PMID- 29351554
TI  - Field data-based mathematical modeling by Bode equations and vector fitting
      algorithm for renewable energy applications.
AB  - The power system always has several variations in its profile due to random load
      changes or environmental effects such as device switching effects when generating
      further transients. Thus, an accurate mathematical model is important because
      most system parameters vary with time. Curve modeling of power generation is a
      significant tool for evaluating system performance, monitoring and forecasting.
      Several numerical techniques compete to fit the curves of empirical data such as
      wind, solar, and demand power rates. This paper proposes a new modified
      methodology presented as a parametric technique to determine the system's
      modeling equations based on the Bode plot equations and the vector fitting (VF)
      algorithm by fitting the experimental data points. The modification is derived
      from the familiar VF algorithm as a robust numerical method. This development
      increases the application range of the VF algorithm for modeling not only in the
      frequency domain but also for all power curves. Four case studies are addressed
      and compared with several common methods. From the minimal RMSE, the results show
      clear improvements in data fitting over other methods. The most powerful features
      of this method is the ability to model irregular or randomly shaped data and to
      be applied to any algorithms that estimating models using frequency-domain data
      to provide state-space or transfer function for the model.

PMID- 29351555
TI  - Omega-3 fatty acid desaturase gene family from two omega-3 sources, Salvia
      hispanica and Perilla frutescens: Cloning, characterization and expression.
AB  - Omega-3 fatty acid desaturase (omega-3 FAD, D15D) is a key enzyme for alpha
      linolenic acid (ALA) biosynthesis. Both chia (Salvia hispanica) and perilla
      (Perilla frutescens) contain high levels of ALA in seeds. In this study, the
      omega-3 FAD gene family was systematically and comparatively cloned from chia and
      perilla. Perilla FAD3, FAD7, FAD8 and chia FAD7 are encoded by single-copy (but
      heterozygous) genes, while chia FAD3 is encoded by 2 distinct genes. Only 1 chia
      FAD8 sequence was isolated. In these genes, there are 1 to 6 transcription start
      sites, 1 to 8 poly(A) tailing sites, and 7 introns. The 5'UTRs of PfFAD8a/b
      contain 1 to 2 purine-stretches and 2 pyrimidine-stretches. An alternative splice
      variant of ShFAD7a/b comprises a 5'UTR intron. Their encoded proteins harbor an
      FA_desaturase conserved domain together with 4 trans-membrane helices and 3
      histidine boxes. Phylogenetic analysis validated their identity of dicot
      microsomal or plastidial omega-3 FAD proteins, and revealed some important
      evolutionary features of plant omega-3 FAD genes such as convergent evolution
      across different phylums, single-copy status in algae, and duplication events in
      certain taxa. The qRT-PCR assay showed that the omega-3 FAD genes of two species
      were expressed at different levels in various organs, and they also responded to
      multiple stress treatments. The functionality of the ShFAD3 and PfFAD3 enzymes
      was confirmed by yeast expression. The systemic molecular and functional features
      of the omega-3 FAD gene family from chia and perilla revealed in this study will
      facilitate their use in future studies on genetic improvement of ALA traits in
      oilseed crops.

PMID- 29351556
TI  - Testosterone-induced benign prostatic hyperplasia rat and dog as facile models to
      assess drugs targeting lower urinary tract symptoms.
AB  - Benign prostatic hyperplasia (BPH) is an age-related disease, affecting a
      majority of elderly men worldwide. Medical management of BPH is an alternative to
      surgical treatment of this disease. Currently, alpha1-adrenergic receptor (alpha1
      AR) antagonists are among the first line drugs to treat BPH by reducing the
      tension of urinary track and thus the obstructive symptoms in voiding. In drug
      development, old male dogs with spontaneous BPH are considered the golden
      standard of the animal models. However, old dogs (>6 years) are expensive and not
      all old dogs develop BPH. So it is necessary to develop more accessible animal
      models for drug efficacy evaluation. Here we describe the development of
      testosterone-induced BPH models in both rats and young adult dogs and their
      applications in the in vivo evaluation of alpha1-AR antagonist. The BPH rats and
      dogs induced by chronic testosterone treatment have significantly increased
      micturition frequency and reduced mean voided volume, very similar to the
      clinical symptoms of BPH patients. Silodosin, an alpha1-AR antagonist,
      significantly reduces the urinary frequency and increases the voided volume in
      BPH model animals in a dose-dependent manner. The results demonstrate that
      testosterone-induced BPH rat and dog models might provide a more efficient way to
      evaluate micturition behavior in anti-BPH drug studies.

PMID- 29351557
TI  - Effects of night-time and weekend admissions on in-hospital mortality in acute
      myocardial infarction patients in Japan.
AB  - BACKGROUND: Patients admitted to hospital during off-hours may experience poorer
      quality of care and clinical outcomes. However, few studies have examined the
      variations in clinical processes and outcomes across admission times and days of
      the week in acute myocardial infarction (AMI) patients. This study aimed to
      comparatively analyze the effect of weekend and weekday admissions stratified by
      admission time on in-hospital mortality in AMI patients. METHODS AND RESULTS:
      Using a large nationwide administrative database, we analyzed 103,908 AMI
      patients admitted to 639 Japanese acute care hospitals between April 2011 and
      March 2015. We divided patients into the following 4 groups: weekday daytime
      admissions, weekday night-time admissions, weekend daytime admissions, and
      weekend night-time admissions. A hierarchical logistic regression model was used
      to comparatively examine in-hospital mortality among the groups after adjusting
      for age, sex, ambulance use, Killip class, comorbidities, and the number of
      cardiologists in the admitting hospital. In addition, we also calculated and
      compared the adjusted odds ratios of various AMI therapies among the groups. The
      in-hospital mortality rate of weekend daytime admissions was higher than those
      admitted during other times (weekday daytime: 6.8%; weekday night-time; 6.5%,
      weekend daytime; 7.6%; weekend night-time: 6.6%; P < 0.001), even after adjusting
      for the covariates (adjusted odds ratio for weekend daytime admissions: 1.10; 95%
      confidence interval: 1.03-1.19). The prescription rates of guideline-based
      medications provided on the first day of admission were higher in night-time
      admissions than in daytime admissions. CONCLUSIONS: In-hospital mortality rates
      were higher in AMI patients admitted during weekend daytime hours when compared
      with patients admitted during other times. Furthermore, patients admitted during
      daytime hours had lower prescription rates of guideline-based medications. Our
      findings indicate that weekend daytime admissions may be a potential target for
      improvement in the Japanese healthcare system.

PMID- 29351558
TI  - Analysis of 500 anterior cruciate ligament reconstructions from a private
      institutional register.
AB  - PURPOSE: The aims of this study are to describe the epidemiological
      characteristics of anterior cruciate ligament reconstructions in a private
      hospital in Brazil and to determine trends in medical practice for comparison
      with previous studies. METHODS: We retrospectively reviewed the anterior cruciate
      ligament institutional register to obtain data from all patients who underwent
      primary anterior cruciate ligament reconstruction from July 2014 to June 2016.
      Descriptive statistics were used to summarize the sample. Specific statistical
      tests were used to assess associations between the meniscal lesion and other
      variables. RESULTS: During the study period, 72.6% out of 500 patients were male.
      The mean age at surgery was 35.1 years. The mean age was higher among females
      than among males (37.3 +/- 12.1 vs 34.3 +/- 10.8 years). The median time from
      injury to surgery was 44 days. The most common femoral and tibial fixations used
      were suspensory fixation (60.8%) and interference screw (96%), respectively. The
      most commonly used graft was hamstring tendon (70.2%), followed by bone-patellar
      tendon-bone (28.8%). A meniscal lesion was noted in 44.8% of cases. Partial
      meniscectomy was performed in 69.5% of meniscal lesions, and meniscal repair was
      performed in 14.1% of lesions. The mean length of hospital stay was 1.4 days. The
      proportion of men in the group of patients with an associated meniscal lesion was
      higher than that in the group of patients without a meniscal lesion (p = 0.007).
      CONCLUSIONS: In this study, we identified that the vast majority of surgeries
      were performed in male patients in all age groups, and patients older than 30
      years and with a short time from injury to surgery predominated. Concerning
      surgical technique, we noted a low rate of meniscal repair and a higher
      preference for the use of hamstring graft and suspensory fixation on the femoral
      side.

PMID- 29351559
TI  - Characterisation of ictal and interictal states of epilepsy: A system dynamic
      approach of principal dynamic modes analysis.
AB  - Epilepsy is a brain disorder characterised by the recurrent and unpredictable
      interruptions of normal brain function, called epileptic seizures. The present
      study attempts to derive new diagnostic indices which may delineate between ictal
      and interictal states of epilepsy. To achieve this, the nonlinear modeling
      approach of global principal dynamic modes (PDMs) is adopted to examine the
      functional connectivity of the temporal and frontal lobes with the occipital
      brain segment using an ensemble of paediatric EEGs having the presence of
      epileptic seizure. The distinct spectral characteristics of global PDMs are found
      to be in line with the neural rhythms of brain dynamics. Moreover, we find that
      the linear trends of associated nonlinear functions (ANFs) associated with the
      2nd and 4th global PDMs (representing delta, theta and alpha bands) of Fp1-F3 may
      differentiate between ictal and interictal states of epilepsy. These findings
      suggest that global PDMs and their associated ANFs may offer potential utility as
      diagnostic neural measures for ictal and interictal states of epilepsy.

PMID- 29351560
TI  - The correlation of background parenchymal enhancement in the contralateral breast
      with patient and tumor characteristics of MRI-screen detected breast cancers.
AB  - PURPOSE: Higher background parenchymal enhancement (BPE) could be used for
      stratification of MRI screening programs since it might be related to a higher
      breast cancer risk. Therefore, the purpose of this study is to correlate BPE to
      patient and tumor characteristics in women with unilateral MRI-screen detected
      breast cancer who participated in an intermediate and high risk screening
      program. As BPE in the affected breast may be difficult to discern from enhancing
      cancer, we assumed that BPE in the contralateral breast is a representative
      measure for BPE in women with unilateral breast cancer. MATERIALS AND METHODS:
      This retrospective study was approved by our local institutional board and a
      waiver for consent was granted. MR-examinations of women with unilateral breast
      cancers screen-detected on breast MRI were evaluated by two readers. BPE in the
      contralateral breast was rated according to BI-RADS. Univariate analyses were
      performed to study associations. Observer variability was computed. RESULTS:
      Analysis included 77 breast cancers in 76 patients (age: 48+/-9.8 years),
      including 62 invasive and 15 pure ductal carcinoma in-situ cases. A negative
      association between BPE and tumor grade (p<=0.016) and a positive association
      with progesterone status (p<=0.021) was found. The correlation was stronger when
      only considering invasive disease. Inter-reader agreement was substantial.
      CONCLUSION: Lower BPE in the contralateral breast in women with unilateral breast
      cancer might be associated to higher tumor grade and progesterone receptor
      negativity. Great care should be taken using BPE for stratification of patients
      to tailored screening programs.

PMID- 29351561
TI  - Preconception use of cART by HIV-positive pregnant women increases the risk of
      infants being born small for gestational age.
AB  - BACKGROUND: The benefits of combination anti-retroviral therapy (cART) in HIV
      positive pregnant women (improved maternal health and prevention of mother to
      child transmission [pMTCT]) currently outweigh the adverse effects due to cART.
      As the variety of cART increases, however, the question arises as to which type
      of cART is safest for pregnant women and women of childbearing age. We studied
      the effect of timing and exposure to different classes of cART on adverse birth
      outcomes in a large HIV cohort in the Netherlands. MATERIALS AND METHODS: We
      included singleton HEU infants registered in the ATHENA cohort from 1997 to 2015.
      Multivariate logistic regression analysis for single and multiple pregnancies was
      used to evaluate predictors of small for gestational age (SGA, birth weight <10th
      percentile for gestational age), low birth weight and preterm delivery. RESULTS:
      A total of 1392 children born to 1022 mothers were included. Of these, 331
      (23.8%) children were SGA. Women starting cART before conception had an increased
      risk of having a SGA infant compared to women starting cART after conception (OR
      1.35, 95% CI 1.03-1.77, p = 0.03). The risk for SGA was highest in women who
      started a protease inhibitor-(PI) based regimen prior to pregnancy, compared with
      women who initiated PI-based cART during pregnancy. While the association of
      preterm delivery and preconception cART was significant in univariate analysis,
      on multivariate analysis only a non-significant trend was observed (OR 1.39, 95%
      CI 0.94-1.92, p = 0.06) in women who had started cART before compared to after
      conception. In multivariate analysis, the risk of low birth weight (OR 1.34, 95%
      CI 0.94-1.92, p = 0.11) was not significantly increased in women who had started
      cART prior to conception compared to after conception. CONCLUSION: In our cohort
      of pregnant HIV-positive women, the use of cART prior to conception, most notably
      a PI-based regimen, was associated with intrauterine growth restriction resulting
      in SGA. Data showed a non-significant trend in the risk of PTD associated with
      preconception use of cART compared to its use after conception. More studies are
      needed with regard to the mechanisms taking place in the placenta during fetal
      growth in pregnant HIV-positive women using cART. It will only be with this
      knowledge that we can begin to understand the potential impact of HIV and cART on
      the fetus, in order to be able to determine the optimal individualised drug
      regimen for HIV-infected women of childbearing age.

PMID- 29351562
TI  - Clinical and ultrasonographic features associated to response to intraarticular
      corticosteroid injection. A one year follow up prospective cohort study in knee
      osteoarthritis patient with joint effusion.
AB  - OBJECTIVES: Intraarticular injection is used for pain relief in knee
      osteoarthritis (OA), but there is not a well defined profile of patient who could
      get more benefit from it. The purpose of this study was to evaluate the frequency
      of pain relief at one year after corticosteroids intraarticular injection and to
      identify clinical factors associated to response in patients with knee
      osteoarthritis with joint effusion. METHODS: One-year prospective cohort study of
      patients with knee OA with joint effusion confirmed by ultrasound. An
      intraarticular injection was performed following a clinical protocol.
      Anthropometric measurements, laboratory parameters, clinical severity, ultrasound
      parameters and radiological severity were collected. Response regarding pain and
      presence of synovial fluid on ultrasound at one month and at one year were
      evaluated. Clinical responder were consider in subjects with enough improvement
      to carry out normal daily activities with pain VAS<40mm. RESULTS: One hundred and
      thirty-two patients were included.A significant number of patients (61.4%)
      improved pain at one year following the protocol established in this study. Pain
      and ultrasound synovial fluid at one month appeared to predict the response at
      one year. The Lequesne index and the percentage of body fat were independently
      associated to pain at one year while the Lequesne index and ultrasound synovial
      hypertrophy were independently related to the presence of synovial fluid at one
      year. CONCLUSIONS: The status regarding pain or ultrasound synovial fluid at one
      month after an intraarticular joint injection appeared to predict the status at
      one year in patients with knee osteoarthritis and synovial effusion.

PMID- 29351563
TI  - A consensus linkage map of lentil based on DArT markers from three RIL mapping
      populations.
AB  - BACKGROUND: Lentil (Lens culinaris ssp. culinaris Medikus) is a diploid (2n = 2x
      = 14), self-pollinating grain legume with a haploid genome size of about 4 Gbp
      and is grown throughout the world with current annual production of 4.9 million
      tonnes. MATERIALS AND METHODS: A consensus map of lentil (Lens culinaris ssp.
      culinaris Medikus) was constructed using three different lentils recombinant
      inbred line (RIL) populations, including "CDC Redberry" x "ILL7502" (LR8),
      "ILL8006" x "CDC Milestone" (LR11) and "PI320937" x "Eston" (LR39). RESULTS: The
      lentil consensus map was composed of 9,793 DArT markers, covered a total of
      977.47 cM with an average distance of 0.10 cM between adjacent markers and
      constructed 7 linkage groups representing 7 chromosomes of the lentil genome. The
      consensus map had no gap larger than 12.67 cM and only 5 gaps were found to be
      between 12.67 cM and 6.0 cM (on LG3 and LG4). The localization of the SNP markers
      on the lentil consensus map were in general consistent with their localization on
      the three individual genetic linkage maps and the lentil consensus map has longer
      map length, higher marker density and shorter average distance between the
      adjacent markers compared to the component linkage maps. CONCLUSION: This high
      density consensus map could provide insight into the lentil genome. The consensus
      map could also help to construct a physical map using a Bacterial Artificial
      Chromosome library and map based cloning studies. Sequence information of DArT
      may help localization of orientation scaffolds from Next Generation Sequencing
      data.

PMID- 29351564
TI  - Steatosis in South African women: How much and why?
AB  - BACKGROUND: Globally, steatosis is the commonest type of liver pathology and is
      closely associated with obesity and the metabolic syndrome. Obesity is common in
      urban African females but no data is available on hepatic fat content in this
      population group when compared to other ethnic groups. The aim of this study was
      therefore to compare hepatic fat content in woman from different ethnic groups in
      South Africa and to characterise the principle determinants of liver fat.
      MATERIALS AND METHODS: A convenience sample of 106 (48 Indian, 29 African and 29
      Caucasian) female volunteers aged 20-60 years and having no history of
      cardiometabolic disorders were recruited. Hepatic fat was determined from CT
      scans using the liver-spleen attenuation ratio (LAR), which decreases with
      increasing levels of hepatic fat. Anthropometric and cardiometabolic parameters
      were measured with insulin resistance determined using the HOMA index and
      dysglycaemia defined as fasting glucose >=5.60 mmol/L. RESULTS: The African
      subjects had significantly lower hepatic fat content (LAR as median
      [interquartile range]: 1.35 [1.28, 1.41]) than the Indian (1.22 [1.10, 1.35];
      p<0.005) and Caucasian (1.27 [1.16, 1.33]; p<0.05) females even though they had
      significantly higher BMIs than both groups (p<0.0005 and p<0.05, respectively).
      Linear regression showed that: subcutaneous abdominal fat was a significant
      (unstandardised beta = 0.007; p = 0.03) negative, whilst insulin resistance (beta
      = -0.97; p = 0.01) and dysglycaemia (beta = -3.58; p = 0.01) were significant
      positive determinants of liver fat; higher hepatic fat levels in subjects with
      the metabolic syndrome were explained by insulin resistance and dysglycaemia.
      DISCUSSION: African ethnicity is associated with low liver fat content.
      Subcutaneous abdominal fat protects against steatosis, possibly by acting as a
      triglyceride reservoir. Insulin resistance and dysglycaemia lead to greater
      hepatic fat deposition and explain higher liver fat levels in subjects with the
      metabolic syndrome. These observations must be further investigated in
      longitudinal surveys.

PMID- 29351566
TI  - Patterns in reef fish assemblages: Insights from the Chagos Archipelago.
AB  - Understanding the drivers of variability in the composition of fish assemblages
      across the Indo-Pacific region is crucial to support coral reef ecosystem
      resilience. Whilst numerous relationships and feedback mechanisms between the
      functional roles of coral reef fishes and reef benthic composition have been
      investigated, certain key groups, such as the herbivores, are widely suggested to
      maintain reefs in a coral-dominated state. Examining links between fishes and
      reef benthos is complicated by the interactions between natural processes,
      disturbance events and anthropogenic impacts, particularly fishing pressure. This
      study examined fish assemblages and associated benthic variables across five
      atolls within the Chagos Archipelago, where fishing pressure is largely absent,
      to better understand these relationships. We found high variability in fish
      assemblages among atolls and sites across the archipelago, especially for key
      groups such as a suite of grazer-detritivore surgeonfish, and the parrotfishes
      which varied in density over 40-fold between sites. Differences in fish
      assemblages were significantly associated with variable levels of both live and
      recently dead coral cover and rugosity. We suggest these results reflect
      differing coral recovery trajectories following coral bleaching events and a
      strong influence of 'bottom-up' control mechanisms on fish assemblages. Species
      level analyses revealed that Scarus niger, Acanthurus nigrofuscus and Chlorurus
      strongylocephalos were key species driving differences in fish assemblage
      structure. Clarifying the trophic roles of herbivorous and detritivorous reef
      fishes will require species-level studies, which also examine feeding behaviour,
      to fully understand their contribution in maintaining reef resilience to climate
      change and fishing impacts.

PMID- 29351565
TI  - SUMO targeting of a stress-tolerant Ulp1 SUMO protease.
AB  - SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation
      and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO
      conjugates rapidly increase in response to cellular stress, including nutrient
      starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other
      proteotoxic stressors. Nevertheless, little is known about the regulation and
      targeting of SUMO proteases during stress. To this end we have undertaken a
      detailed comparison of the SUMO-binding activity of the budding yeast protein
      Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces
      marxianus, KmUlp1. We find that the catalytic UD domains of both ScUlp1 and
      KmUlp1 show a high degree of sequence conservation, complement a ulp1Delta mutant
      in vivo, and process a SUMO precursor in vitro. Next, to compare the SUMO
      trapping features of both SUMO proteases we produced catalytically inactive
      recombinant fragments of the UD domains of ScUlp1 and KmUlp1, termed ScUTAG and
      KmUTAG respectively. Both ScUTAG and KmUTAG were able to efficiently bind a
      variety of purified SUMO isoforms and bound immobilized SUMO1 with nanomolar
      affinity. However, KmUTAG showed a greatly enhanced ability to bind SUMO and SUMO
      modified proteins in the presence of oxidative, temperature and other stressors
      that induce protein misfolding. We also investigated whether a SUMO-interacting
      motif (SIM) in the UD domain of KmULP1 that is not conserved in ScUlp1 may
      contribute to the SUMO-binding properties of KmUTAG. In summary, our data reveal
      important details about how SUMO proteases target and bind their sumoylated
      substrates, especially under stress conditions. We also show that the robust pan
      SUMO binding features of KmUTAG can be exploited to detect and study SUMO
      modified proteins in cell culture systems.

PMID- 29351567
TI  - Whole thorax irradiation of non-human primates induces persistent nuclear damage
      and gene expression changes in peripheral blood cells.
AB  - We investigated the cytogenetic and gene expression responses of peripheral blood
      cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax
      irradiated with a single dose of 10 Gy. In this model, partial irradiation of
      NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the
      study of late radiation-induced lung injury, while avoiding acute radiation
      syndromes related to hematopoietic and gastrointestinal injury. A transient drop
      in circulating lymphocytes and platelets was seen by 9 days, followed by
      elevations in respiratory rate, circulating neutrophils, lymphocytes, and
      monocytes at 60-100 days, corresponding to computed tomography (CT) and
      histologic evidence of pneumonitis, and elective euthanasia of four animals. To
      evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy
      WTLI, we used the cytokinesis-block micronucleus (CBMN) assay to measure
      chromosomal aberrations as post-mitotic micronuclei in blood samples collected up
      to 8 months after irradiation. Regression analysis showed significant induction
      of micronuclei in NHP blood cells that persisted with a gradual decline over the
      8-month study period, suggesting long-term DNA damage in blood lymphocytes after
      WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We
      isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30
      days after irradiation. We identified 1187 transcripts that were significantly
      changed across the 30-day time course. From changes in gene expression, we
      identified biological processes related to immune responses, which persisted
      across the 30-day study. Response to oxygen-containing compounds and bacteria
      were implicated by gene-expression changes at the earliest day 2 and latest, day
      30 time-points. Gene expression changes suggest a persistent altered state of the
      immune system, specifically response to infection, for at least a month after
      WTLI.

PMID- 29351569
TI  - Neighborhood disadvantage and body mass index: a study of residential relocation.
AB  - Natural experiments, such as longitudinal observational studies which follow-up
      residents as they relocate, provide a strong basis to infer causation between the
      neighborhood environment and health. This study examined whether changes in the
      level of neighborhood disadvantage were associated with changes in body mass
      index (BMI) following residential relocation. This analysis included data from
      928 residents who relocated between 2007 and 2013, across four waves of the
      HABITAT study in Brisbane, Australia. Neighborhood disadvantage was measured
      using a census-derived composite index. For individual-level data participants
      self-reported their height, weight, education, occupation and household income.
      Data were analyzed using multilevel (hybrid) linear models. Women residing in
      less disadvantaged neighborhoods had a lower BMI, but there was no association
      among men. Neighborhood disadvantage was not associated with within-individual
      changes in BMI among men or women when moving to a new neighborhood. Despite a
      growing body of literature suggesting an association between neighborhood
      disadvantage and BMI, the current study suggests that this association may not be
      causal among mid-older aged adults. Observing associations between neighborhood
      socioeconomic disadvantage and BMI over the life course, including the impact of
      residential relocation in the younger years remains a priority for future
      research.

PMID- 29351568
TI  - Habits and beliefs related to food supplements: Results of a survey among Italian
      students of different education fields and levels.
AB  - The increasing availability of food supplements, aggressive media advertising,
      and common beliefs that these substances have only positive effects on health and
      sport performance indicate a need for continuous monitoring of this phenomenon.
      The aim of this study was to investigate the habits and beliefs related to diet
      supplementation among medical, health professional, and other university/high
      school students by means of a cross-sectional anonymous survey online. Among the
      respondents aware of supplements, 37.4% were taking or had taken them in the
      past. Food supplement use was more common among university students (in
      particular, those in health professional graduate courses) than high school
      students. Individual sport practice, rather than team sport, was associated with
      higher likelihood of food supplement use. Multivitamins were most commonly used,
      while weight-loss formulations were the least popular. Strikingly, filling
      nutrient gaps was statistically not considered the main reason for taking food
      supplements. Instead, they were used to enhance mental performance or enhance
      well-being. There was statistical evidence that students not enrolled in health
      or medical professional studies strongly agreed more often than medical students
      that taking food supplements prevents illness. These results indicate a striking
      difference between the evidence-based and personal reasons for food supplement
      use. Arguably, it calls for an improvement in education about diet
      supplementation and a change in attitude of health care providers to its
      implementation.

PMID- 29351570
TI  - Joint adolescent-adult early phase clinical trials to improve access to new drugs
      for adolescents with cancer: proposals from the multi-stakeholder platform
      ACCELERATE.

PMID- 29351571
TI  - The barriers and facilitators for recognising distress in people with severe
      dementia on general hospital wards.
AB  - Introduction: psychological symptoms and delirium are common, but underreported
      in people with dementia on hospital wards. Unrecognised and untreated symptoms
      can manifest as distress. Identifying distress accurately therefore could act as
      a trigger for better investigation and treatment of the underlying causes. The
      challenges faced by healthcare professionals to recognise and report distress are
      poorly understood. Methods: semi-structured interviews with a purposive sample of
      25 healthcare professionals working with older people in general hospitals were
      conducted. Interviews were analysed generating themes that describe the
      facilitators and barriers of recognising and caring for distress in dementia.
      Results: regardless of training or experience all participants had a similar
      understanding of distress, and identified it as a term that is easily understood
      and communicated. All participants believed they recognised distress innately.
      However, the majority also believed it was facilitated by experience, being
      familiar with their patients and listening to the concerns of the person's usual
      carers. Barriers to distress recognition included busy ward environments, and
      that some people may lack the skill to identify distress in hypoactive patients.
      Conclusion: distress may be a simple and easily identified marker of unmet need
      in people with dementia in hospital. However, modifiable and unmodifiable
      barriers are suggested that reduce the chance of distress being identified or
      acted on. Improving our understanding of how distress is identified in this
      environment, and in turn developing systems that overcome these barriers, may
      improve the accuracy with which distress is identified on hospital wards.

PMID- 29351572
TI  - Differential Susceptibility in Ambient Particle-Related Risk of First-Ever
      Stroke: Findings From a National Case-Crossover Study.
AB  - Different populations may respond differently to exposure to ambient fine
      particulate matter, defined as particulate matter with an aerodynamic diameter
      less than or equal to 2.5 MUm (PM2.5); however, less is known about the
      distribution of susceptible individuals among the entire population. We conducted
      a time-stratified case-crossover study to assess associations between stroke risk
      and exposure to PM2.5. During 2013-2015, 1,356 first-ever stroke events were
      derived from a large representative sample, the China National Stroke Screening
      Survey (CNSSS) database. Daily PM2.5 average exposures with a spatial resolution
      of 0.1 degrees  were estimated using a data assimilation approach combining
      satellite measurements, air model simulations, and monitoring values. The
      distribution of susceptibility was derived according to individual-specific
      associations with PM2.5 modified by different combinations of individual-level
      characteristics and their joint frequencies among all of the CNSSS participants
      (n = 1,292,010). We found that first-ever stroke was statistically significantly
      associated with PM2.5 (per 10-MUg/m3 increment of exposure, odds ratio = 1.049,
      95% confidence interval (CI): 1.038, 1.061). This association was modified by
      demographic (e.g., sex), lifestyle (e.g., overweight/obesity), and medical
      history (e.g., diabetes) variables. The combined association with PM2.5 varied
      from 0.966 (95% CI: 0.920, 1.013) to 1.145 (95% CI: 1.080, 1.215) per 10-MUg/m3
      increment in different subpopulations. We found that most of the CNSSS
      participants were at increased risk of PM2.5-related stroke, while only a small
      proportion were highly susceptible.

PMID- 29351573
TI  - Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung
      cancer.
AB  - Background: Various programed death ligand 1 (PD-L1) immunohistochemistry (IHC)
      assays have been developed and used in clinical trials in association with
      different drugs. In order to harmonize and make PD-L1 testing in non-small-cell
      lung cancer (NSCLC) widely available, we conducted a multicenter study comparing
      PD-L1 standardized assays and laboratory-developed tests (LDTs). Methods: IHC
      with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263)
      was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using
      Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark
      Ultra (2 centers) platforms. For each matching platform, 22C3, 28-8 and SP263
      assays were performed. For nonmatching platforms and other antibodies, LDTs were
      developed in each center. A total of 35 stainings were performed for each case
      across different platforms and antibodies. PD-L1 staining was assessed in tumor
      cells and immune cells by seven trained thoracic pathologists. For statistical
      analysis, 1%, 50% and 1%, 5%, 10% expression thresholds were used for tumor cells
      and immune cells, respectively. Results: 28-8, 22C3 and SP263 assays were highly
      concordant for tumor cells staining across the five Dako or Ventana platforms.
      Among 27 LDTs developed in 7 centers on Dako, Ventana and Leica platforms, 14
      (51.8%) demonstrated similar concordance when compared with reference assays for
      tumor cell staining. Clone SP263 achieved the highest concordance rate across all
      platforms. Lower concordance was observed for immune cells staining when using a
      four categories scale. Conclusion: 28-8, 22C3 and SP263 assays had close
      analytical performance for tumor cell staining across seven centers. Some LDTs on
      Dako, Ventana and Leica platforms achieved similar concordance, but caution is
      warranted for their validation. These LDTs will be further validated in order to
      provide recommendations for the use of assays and LDT for PD-L1 testing in NSCLC.

PMID- 29351575
TI  - Waterlogging tolerance, tissue nitrogen and oxygen transport in the forage legume
      Melilotus siculus: a comparison of nodulated and nitrate-fed plants.
AB  - Background and Aims: Soil waterlogging adversely impacts most plants. Melilotus
      siculus is a waterlogging-tolerant annual forage legume, but data were lacking
      for the effects of root-zone hypoxia on nodulated plants reliant on N2 fixation.
      The aim was to compare the waterlogging tolerance and physiology of M. siculus
      reliant on N2 fixation or with access to NO3-. Methods: A factorial experiment
      imposed treatments of water level (drained or waterlogged), rhizobia (nil or
      inoculated) and mineral N supply (nil or 11 mm NO3-) for 21 d on plants in pots
      of vermiculite in a glasshouse. Nodulation, shoot and root growth and tissue N
      were determined. Porosity (gas volume per unit tissue volume) and respiration
      rates of root tissues and nodules, and O2 microelectrode profiling across
      nodules, were measured in a second experiment. Key Results: Plants inoculated
      with the appropriate rhizobia, Ensifer (syn. Sinorhizobium) medicae, formed
      nodules. Nodulated plants grew as well as plants fed NO3-, both in drained and
      waterlogged conditions. The growth and total N content of nodulated plants
      (without any NO3- supplied) indicated N2 fixation. Respiration rates (mass basis)
      were highest in nodules and root tips and lowest in basal root tissues. Secondary
      aerenchyma (phellem) formed along basal root parts and a thin layer of this
      porous tissue also covered nodules, which together enhanced gas-phase diffusion
      of O2 to the nodules; O2 was below detection within the infected zone of the
      nodule interior. Conclusions: Melilotus siculus reliant on N2 fixation grew well
      both in drained and waterlogged conditions, and had similar tissue N
      concentrations. In waterlogged conditions the relatively high respiration rates
      of nodules must rely on O2 movement via the aerenchymatous phellem in hypocotyl,
      roots and the outer tissue layers of nodules.

PMID- 29351574
TI  - Self-Reported Knowledge, Correct Knowledge and use of UK Drinking Guidelines
      Among a Representative Sample of the English Population.
AB  - Aims: Promotion of lower risk drinking guidelines is a commonly used public
      health intervention with various purposes, including communicating alcohol
      consumption risks, informing drinkers' decision-making and, potentially, changing
      behaviour. UK drinking guidelines were revised in 2016. To inform potential
      promotion of the new guidelines, we aimed to examine public knowledge and use of
      the previous drinking guidelines, including by population subgroup. Methods: A
      demographically representative, cross-sectional online survey of 2100 adults
      living in England in July 2015 (i.e. two decades after adoption of previous
      guidelines and prior to introduction of new guidelines). Univariate and
      multivariate logistic regressions examined associations between demographic
      variables, alcohol consumption (AUDIT-C), smoking, and knowledge of health
      conditions and self-reported knowledge and use of drinking guidelines.
      Multinomial logistic regression examined the same set of variables in relation to
      accurate knowledge of drinking guidelines (underestimation, accurate-estimation,
      overestimation). Results: In total, 37.8% of drinkers self-reported knowing their
      own-gender drinking guideline, of whom 66.2% gave an accurate estimate. Compared
      to accurate estimation, underestimation was associated with male gender, lower
      education and AUDIT-C score, while overestimation was associated with smoking.
      Few (20.8%) reported using guidelines to monitor drinking at least sometimes.
      Drinking guideline use was associated with higher education, overestimating
      guidelines and lower AUDIT-C. Correctly endorsing a greater number of health
      conditions as alcohol-related was associated with self-reported knowledge of
      guidelines, but was not consistently associated with accurate estimation or use
      to monitor drinking. Conclusions: Two decades after their introduction, previous
      UK drinking guidelines were not well known or used by current drinkers. Those who
      reported using them tended to overestimate recommended daily limits. SHORT
      SUMMARY: We examined public knowledge and use of UK drinking guidelines just
      before new guidelines were released (2016). Despite previous guidelines being in
      place for two decades, only one in four drinkers accurately estimated these, with
      even fewer using guidelines to monitor drinking. Approximately 8% of drinkers
      overestimated maximum daily limits.

PMID- 29351576
TI  - Nivolumab-associated bone marrow necrosis.

PMID- 29351577
TI  - Effects of excess thromboxane A2 on placental development and nutrient
      transporters in a Mus musculus model of fetal growth restriction.
AB  - Hypertensive disease of pregnancy (HDP) with placental insufficiency is the most
      common cause of fetal growth restriction (FGR) in the developed world. Despite
      the known negative consequences of HDP both to the mother and fetus, little is
      known about the longitudinal placental changes that occur as HDP progresses in
      pregnancy. This is because longitudinal sampling of human placentae during each
      gestation is impossible. Therefore, using a mouse model of thromboxane A2-analog
      infusion to mimic human HDP in the last trimester, we calculated placental
      efficiencies based on fetal and placental weights; quantified spongiotrophoblast
      and labyrinth thicknesses and vascular density within these layers; examined
      whether hypoxia signaling pathway involving vascular endothelial growth factor A
      (VEGFA) and its receptors (VEGFR1, VEGFR2) and matrix metalloproteinases (MMPs)
      contributed to vascular change; and examined nutrient transporter abundance
      including glucose transporters 1 and 3 (GLUT1, GLUT3), neutral amino acid
      transporters 1, 2, and 4 (SNAT1, SNAT2, and SNAT4), fatty acid transporters 2 and
      4 (FATP2, FATP4), and fatty acid translocase (CD36) from embryonic day 15.5 to 19
      in a 20-day C57Bl/6J mouse gestation. We conclude that early-to-mid gestation
      hypertensive placentae show compensatory mechanisms to preserve fetal growth by
      increasing placental efficiencies and maintaining abundance of important nutrient
      transporters. As placental vascular network diminishes over late hypertension,
      placental efficiency diminishes and fetal growth fails. Neither hypoxia signaling
      pathway nor MMPs mediated the vascular diminution in this model. Hypertensive
      placentae surprisingly exhibit a sex-differential expression of nutrient
      transporters in late gestation despite showing fetal growth failure in both
      sexes.

PMID- 29351578
TI  - Circulating tumour DNA analyses reveal novel resistance mechanisms to CDK
      inhibition in metastatic breast cancer.

PMID- 29351579
TI  - Lack of Methyl-CpG Binding Protein 2 (MeCP2) Affects Cell Fate Refinement During
      Embryonic Cortical Development.
AB  - During differentiation, neurons progressively restrict their fate repressing the
      expression of specific genes. Here we describe the involvement in such
      developmental steps of the methyl-CpG binding protein 2 (MeCP2), an epigenetic
      factor that participates to chromatin folding and transcriptional regulation. We
      previously reported that, due to transcriptional impairments, the maturation of
      Mecp2 null neurons is delayed. To evaluate whether this could stem from altered
      progenitors proliferation and differentiation, we investigated whether lack of
      Mecp2 affects these features both in vitro and in vivo. We show that in Mecp2
      null embryonic cortexes the expression of genes defining the identity of
      proliferating neuroprogenitors is enriched and that their permanence in the G1
      phase is prolonged. Moreover, the number of cells transitioning from a stage of
      maturation to a more mature one is increased in Mecp2 null embryonic cortices, in
      line with the central role of G1 for cell identity refinement. We thus suggest
      that, possibly due to the lack of proper transcriptional control normally exerted
      by Mecp2, fate refinement is impaired in developing null cells. We propose that
      the maturation delay affecting the developing Mecp2 null cortex originates, at
      least in part, from deranged mechanisms of cell fate refinement.

PMID- 29351580
TI  - Maternal nutrient restriction impairs young adult offspring ovarian signaling
      resulting in reproductive dysfunction and follicle loss.
AB  - Reproductive abnormalities are included as health complications in offspring
      exposed to poor prenatal nutrition. We have previously shown in a rodent model
      that offspring born to nutrient restriction during pregnancy are born small,
      enter puberty early, and display characteristics of early ovarian aging as
      adults. The present study investigated whether key proteins involved in follicle
      recruitment and growth mediate ovarian follicle loss. Pregnant rats were
      randomized to a standard diet throughout pregnancy and lactation (CON), or a
      calorie-restricted (50% of control) diet (UN) during pregnancy. Offspring
      reproductive phenotype was investigated at postnatal days 4, 27, and 65. Maternal
      UN resulted in young adult (P65) irregular estrous cyclicity due to persistent
      estrus, a significant loss of antral follicles, corpora lutea, and an increase in
      atretic follicles. This decrease in growing follicles in UN offspring appears to
      be due to increased apoptosis as seen by immunopositive staining of pro-apoptotic
      factor CASP3 (caspase 3) in ovaries of young adult offspring. UN prepubertal
      offspring had reduced expression levels of Fshr in antral follicles, which may
      contribute to a decrease in PI3K/AKT activation evident as a decrease in pAKT
      immunolocalization in prepubertal antral follicles. Moreover, neonatal ovaries of
      UN offspring show decreased levels of immunopositive staining for AMHR2 (anti
      mullerian hormone receptor 2). Collectively, these data demonstrate that maternal
      UN during pregnancy impacts ovarian function in offspring as early as P65 and
      provides a model for understanding the mechanisms driving early life UN-induced
      follicle loss and reproductive dysfunction.

PMID- 29351512
TI  - Physiology of Astroglia.
AB  - Astrocytes are neural cells of ectodermal, neuroepithelial origin that provide
      for homeostasis and defense of the central nervous system (CNS). Astrocytes are
      highly heterogeneous in morphological appearance; they express a multitude of
      receptors, channels, and membrane transporters. This complement underlies their
      remarkable adaptive plasticity that defines the functional maintenance of the CNS
      in development and aging. Astrocytes are tightly integrated into neural networks
      and act within the context of neural tissue; astrocytes control homeostasis of
      the CNS at all levels of organization from molecular to the whole organ.

PMID- 29351581
TI  - Unifying control over the body: consciousness and cross-cueing in split-brain
      patients.

PMID- 29351582
TI  - SCO2 mutations cause early-onset axonal Charcot-Marie-Tooth disease associated
      with cellular copper deficiency.
AB  - Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome
      c oxidase (COX) assembly protein, have been reported in several cases with fatal
      infantile cardioencephalomyopathy with COX deficiency. Significantly expanding
      the known phenotypic spectrum, we identified compound heterozygous variants in
      SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot
      Marie-Tooth disease type 4. Different from previously described cases, our
      patients developed predominantly motor neuropathy, they survived infancy, and
      they have not yet developed the cardiomyopathy that causes death in early infancy
      in reported patients. Both of our patients harbour missense mutations near the
      conserved copper-binding motif (CXXXC), including the common pathogenic variant
      E140K and a novel change D135G. In addition, each patient carries a second
      mutation located at the same loop region, resulting in compound heterozygote
      changes E140K/P169T and D135G/R171Q. Patient fibroblasts showed reduced levels of
      SCO2, decreased copper levels and COX deficiency. Given that another Charcot
      Marie-Tooth disease gene, ATP7A, is a known copper transporter, our findings
      further underline the relevance of copper metabolism in Charcot-Marie-Tooth
      disease.

PMID- 29351583
TI  - Travelers' Diarrhea in Thailand: A Quantitative Analysis Using TaqMan(r) Array
      Card.
AB  - Background: Travelers' diarrhea (TD) is a common illness experienced by travelers
      from developed countries who visit developing countries. Recent questionnaire
      based surveillance studies showed that approximately 6%-16% of travelers
      experienced TD while visiting Thailand; however, a majority of TD information was
      limited mainly to US military populations. Methods: A TD surveillance study was
      conducted at Bumrungrad International Hospital in 2012-2014 in Bangkok, Thailand.
      Enteropathogens were identified using conventional methods and the TaqMan(r)
      array card (TAC), which uses real-time polymerase chain reaction for the
      simultaneous detection of multiple pathogens. Analyses to determine pathogen
      disease and symptoms association were performed to elucidate the clinical
      relevance of each enteropathogen. Results: TAC identified more pathogens per
      sample than conventional methods. Campylobacter spp. were the most prevalent,
      followed by the diarrheagenic Escherichia coli and norovirus GII. These agents
      had significant pathogen-disease associations as well as high attributable
      fractions among diarrheal cases. A wide range of pathogen loads for Campylobacter
      spp. was associated with TD, while heat-labile toxin enterotoxigenic Escherichia
      coli was associated with an increased pathogen load. Most cases were associated
      with inflammatory diarrhea, while Campylobacter spp. and Shigella spp. were
      associated with dysentery. Conclusions: A pan-molecular diagnostic method such as
      TAC produces quantifiable and comparable results of all tested pathogens, thereby
      reducing the variability associated with multiple conventional methods. This
      allows better determination of the clinical relevance of each diarrhea etiologic
      agent, as well as their geographical relevance in Thailand.

PMID- 29351586
TI  - Computational deconvolution of transcriptomics data from mixed cell populations.
AB  - Summary: Gene expression analyses of bulk tissues often ignore cell type
      composition as an important confounding factor, resulting in a loss of signal
      from lowly abundant cell types. In this review, we highlight the importance and
      value of computational deconvolution methods to infer the abundance of different
      cell types and/or cell type-specific expression profiles in heterogeneous samples
      without performing physical cell sorting. We also explain the various
      deconvolution scenarios, the mathematical approaches used to solve them and the
      effect of data processing and different confounding factors on the accuracy of
      the deconvolution results. Contact: katleen.depreter@ugent.be. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29351585
TI  - Core Differences in Synaptic Signaling Between Primary Visual and Dorsolateral
      Prefrontal Cortex.
AB  - Neurons in primary visual cortex (V1) are more resilient than those in
      dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's
      disease. The current study compared glutamate and neuromodulatory actions in
      macaque V1 to those in dlPFC, and found striking regional differences. V1
      neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA
      receptor contributions, while dlPFC depends primarily on NMDA receptors.
      Neuromodulatory actions also differed between regions. In V1, cAMP signaling
      increased neuronal firing, and the phosphodiesterase PDE4A was positioned to
      regulate cAMP effects on glutamate release from axons. HCN channels in V1 were
      classically located on distal dendrites, and enhanced cell firing. These data
      contrast with dlPFC, where PDE4A and HCN channels are concentrated in thin
      spines, and cAMP-HCN signaling gates inputs and weakens firing. These regional
      differences may explain why V1 neurons are more resilient than dlPFC neurons to
      the challenges of age and disease.

PMID- 29351584
TI  - The Roles of Left Versus Right Anterior Temporal Lobes in Semantic Memory: A
      Neuropsychological Comparison of Postsurgical Temporal Lobe Epilepsy Patients.
AB  - The presence and degree of specialization between the anterior temporal lobes
      (ATLs) is a key issue in debates about the neural architecture of semantic
      memory. Here, we comprehensively assessed multiple aspects of semantic cognition
      in a large group of postsurgical temporal lobe epilepsy (TLE) patients with left
      versus right anterior temporal lobectomy (n = 40). Both subgroups showed deficits
      in expressive and receptive verbal semantic tasks, word and object recognition,
      naming and recognition of famous faces and perception of faces and emotions.
      Graded differences in performance between the left and right groups were
      secondary to the overall mild semantic impairment; primarily, left resected TLE
      patients showed weaker performance on tasks that required naming or accessing
      semantic information from a written word. Right resected TLE patients were
      relatively more impaired at recognizing famous faces as familiar, although this
      effect was observed less consistently. These findings unify previous partial,
      inconsistent results and also align directly with fMRI and transcranial magnetic
      stimulation results in neurologically intact participants. Taken together, these
      data support a model in which the 2 ATLs act as a coupled bilateral system for
      the representation of semantic knowledge, and in which graded hemispheric
      specializations emerge as a consequence of differential connectivity to
      lateralized speech production and face perception regions.

PMID- 29351587
TI  - Heat exposure induces oxidative stress and DNA damage in the male germ line.
AB  - The reproductive consequences of global warming are not currently understood. In
      order to address this issue, we have examined the reproductive consequences of
      exposing male mice to a mild heat stress. For this purpose, adult male mice were
      exposed to an elevated ambient temperature of 35 degrees C under two exposure
      models. The first involved acute exposure for 24 h, followed by recovery periods
      between 1 day and 6 weeks. The alternative heating regimen involved a daily
      exposure of 8 h for periods of 1 or 2 weeks. In our acute model, we identified
      elevated sperm mitochondrial ROS generation (P < 0.05), increased sperm membrane
      fluidity (P < 0.05), DNA damage in the form of single-strand breaks (P < 0.001),
      and oxidative DNA damage (P < 0.05), characteristic of an oxidative stress
      cascade. This DNA damage was detected in pachytene spermatocytes (P < 0.001) and
      round spermatids (P < 0.001) isolated from testes after 1 day heat recovery.
      Despite these lesions, the spermatozoa of heat-treated mice exhibited no
      differences in their ability to achieve hallmarks of capacitation or to fertilize
      the oocyte and support development of embryos to the blastocyst stage (all P >
      0.05). Collectively, our acute heat stress model supports the existence of heat
      susceptible stages of germ cell development, with the round spermatids being most
      perturbed and spermatogonial stem cells exhibiting resistance to this insult.
      Such findings were complemented by our chronic heat stress model, which further
      supported the vulnerability of the round spermatid population.

PMID- 29351589
TI  - Reply to the letter to the editor 'Concurrent cisplatin and radiotherapy versus
      cetuximab and radiotherapy, an unsolved problem' by Guler et al.

PMID- 29351590
TI  - Characteristics and evolution of the ecosystem of software tools supporting
      research in molecular biology.
AB  - Daily work in molecular biology presently depends on a large number of
      computational tools. An in-depth, large-scale study of that 'ecosystem' of Web
      tools, its characteristics, interconnectivity, patterns of usage/citation,
      temporal evolution and rate of decay is crucial for understanding the forces that
      shape it and for informing initiatives aimed at its funding, long-term
      maintenance and improvement. In particular, the long-term maintenance of these
      tools is compromised because of their specific development model. Hundreds of
      published studies become irreproducible de facto, as the software tools used to
      conduct them become unavailable. In this study, we present a large-scale survey
      of >5400 publications describing Web servers within the two main bibliographic
      resources for disseminating new software developments in molecular biology. For
      all these servers, we studied their citation patterns, the subjects they address,
      their citation networks and the temporal evolution of these factors. We also
      analysed how these factors affect the availability of these servers (whether they
      are alive). Our results show that this ecosystem of tools is highly
      interconnected and adapts to the 'trendy' subjects in every moment. The servers
      present characteristic temporal patterns of citation/usage, and there is a
      worrying rate of server 'death', which is influenced by factors such as the
      server popularity and the institutions that hosts it. These results can inform
      initiatives aimed at the long-term maintenance of these resources.

PMID- 29351588
TI  - Sorghum root-system classification in contrasting P environments reveals three
      main rooting types and root-architecture-related marker-trait associations.
AB  - Background and Aims: Roots facilitate acquisition of macro- and micronutrients,
      which are crucial for plant productivity and anchorage in the soil. Phosphorus
      (P) is rapidly immobilized in the soil and hardly available for plants.
      Adaptation to P scarcity relies on changes in root morphology towards rooting
      systems well suited for topsoil foraging. Root-system architecture (RSA) defines
      the spatial organization of the network comprising primary, lateral and stem
      derived roots and is important for adaptation to stress conditions. RSA
      phenotyping is a challenging task and essential for understanding root
      development. Methods: In this study, 19 traits describing RSA were analysed in a
      diversity panel comprising 194 sorghum genotypes, fingerprinted with a 90-k
      single-nucleotide polymorphism (SNP) array and grown under low and high P
      availability. Key Results: Multivariate analysis was conducted and revealed three
      different RSA types: (1) a small root system; (2) a compact and bushy rooting
      type; and (3) an exploratory root system, which might benefit plant growth and
      development if water, nitrogen (N) or P availability is limited. While several
      genotypes displayed similar rooting types in different environments, others
      responded to P scarcity positively by developing more exploratory root systems,
      or negatively with root growth suppression. Genome-wide association studies
      revealed significant quantitative trait loci (P < 2.9 * 10-6) on chromosomes SBI
      02, SBI-03, SBI-05 and SBI-09. Co-localization of significant and suggestive (P <
      5.7 * 10-5) associations for several traits indicated hotspots controlling root
      system development on chromosomes SBI-02 and SBI-03. Conclusions: Sorghum
      genotypes with a compact, bushy and shallow root system provide potential
      adaptation to P scarcity in the field by allowing thorough topsoil foraging,
      while genotypes with an exploratory root system may be advantageous if N or water
      is the limiting factor, although such genotypes showed highest P uptake levels
      under the artificial conditions of the present study.

PMID- 29351591
TI  - Could seasonally deteriorating environments favour the evolution of autogamous
      selfing and a drought escape physiology through indirect selection? A test of the
      time limitation hypothesis using artificial selection in Clarkia.
AB  - Background and Aims: The evolution of selfing from outcrossing may be the most
      common transition in plant reproductive systems and is associated with a variety
      of ecological circumstances and life history strategies. The most widely
      discussed explanation for these associations is the reproductive assurance
      hypothesis - the proposition that selfing is favoured because it increases female
      fitness when outcross pollen receipt is limited. Here an alternative explanation,
      the time limitation hypothesis, is addressed, one scenario of which proposes that
      selfing may evolve as a correlated response to selection for a faster life cycle
      in seasonally deteriorating environments. Methods: Artificial selection for
      faster maturation (early flowering) or for low herkogamy was performed on Clarkia
      unguiculata (Onagraceae), a largely outcrossing species whose closest relative,
      C. exilis, has evolved higher levels of autogamous selfing. Direct responses to
      selection and correlated evolutionary changes in these traits were measured under
      greenhouse conditions. Direct responses to selection on early flowering and
      correlated evolutionary changes in the node of the first flower, herkogamy,
      dichogamy, gas exchange rates and water use efficiency (WUE) were measured under
      field conditions. Key Results: Lines selected for early flowering and for low
      herkogamy showed consistent, statistically significant responses to direct
      selection. However, there was little or no evidence of correlated evolutionary
      changes in flowering date, floral traits, gas exchange rates or WUE. Conclusions:
      These results suggest that the maturation rate and mating system have evolved
      independently in Clarkia and that the time limitation hypothesis does not explain
      the repeated evolution of selfing in this genus, at least through its indirect
      selection scenario. They also suggest that the life history and physiological
      components of drought escape are not genetically correlated in Clarkia, and that
      differences in gas exchange physiology between C. unguiculata and C. exilis have
      evolved independently of differences in mating system and life history.

PMID- 29351593
TI  - Usefulness of the Serial Measurement of Vi Antibodies.

PMID- 29351592
TI  - Outcome after long-segment tracheal resection: study of 52 cases.
AB  - OBJECTIVES: Resection of long-segment trachea is challenging, and although 50% of
      adult trachea can be removed, anastomotic complications arise proportionally.
      Different release manoeuvres have been described to gain length and reduce
      tension at the suture line. The aim of the study was to evaluate the outcome when
      different release manoeuvres have been utilized during resection and
      reconstruction of the trachea. METHODS: From January 2005 to December 2015, 52
      patients with long segments of trachea >=40 mm requiring resection and
      reconstruction were treated at our institute. Demographic, operative and
      postoperative data were retrospectively analysed. RESULTS: Fifty-two patients
      with long-segment tracheal disorders >=40 mm were analysed in this stud.
      Transient swallowing and phonation dysfunction occurred in 17 (32.2%) patients,
      exclusively in patients who underwent laryngeal release. Swallowing dysfunction
      was Grade I in all patients, except 2 who suffered Grade II dysphagia and were
      relieved in the early postoperative period. Forty-five (86.5%) patients were
      symptom free, and 7 (13.4%) patients were symptomatic (dyspnoea on exertion
      and/or stridor) and required reintervention. Four (7.6%) patients responded to 1
      or 2 sessions of bronchoscopic dilatation, and 3 patients were left with
      permanent tracheostomies. Patients with neoplastic pathology were followed up
      without any neoplastic recurrence. CONCLUSIONS: Long-segment resection and
      reconstruction of the trachea utilizing one or more release manoeuvres can be
      safely done, with low complication rates. Although swallowing and phonation
      dysfunction after laryngeal release were commonly encountered (almost one-third
      of patients), they were mild, transient, self-limited and recovered within 2-3
      weeks of the early postoperative period.

PMID- 29351594
TI  - Seroefficacy of Vi Polysaccharide-Tetanus Toxoid Typhoid Conjugate Vaccine
      (Typbar TCV).
AB  - Background: Salmonella Typhi is the major cause of enteric fever in lower-income
      countries. New conjugate vaccines show promise as public health interventions,
      but there are no efficacy data available from endemic areas. Methods: Data were
      obtained from a previously published phase 3 randomized controlled trial
      comparing Vi polysaccharide-tetanus toxoid conjugate vaccine (Vi-TT) with Vi
      polysaccharide vaccine (Vi-PS) in participants aged 2-45 years. An additional
      open-label arm administered Vi-TT to children aged 6-23 months. The proportion of
      participants with presumed clinical or subclinical infection ("seroincidence")
      was determined using mixture models and compared using relative risks (RRs).
      Results: Of 387 participants, 81 (21%) were classified as having presumed typhoid
      infection during the 2-year postvaccination period. Seroincidence was lower in
      participants randomized to Vi-TT rather than Vi-PS among those aged 2-45 years
      (RR, 0.372; 95% confidence interval [CI], .235-.588; P < .001) and those aged 2
      15 years (RR, 0.424; 95% CI, .231-.778; P = .004). There was no difference in
      seroincidence for Vi-TT between those aged 2-45 years and those aged 6-23 months
      (RR, 1.073; 95% CI, .563-2.046; P = .83). Vaccine seroefficacy was 85% (95% CI,
      80%-88%). Conclusion: This is the first field estimate of the seroefficacy of a
      Vi-TT vaccine and shows that Typbar TCV substantially reduces the number of
      serologically defined clinical or subclinical infections in infants, children,
      and adults. These results support the recent World Health Organization
      recommendations for deployment of typhoid conjugate vaccines in high-burden
      areas.

PMID- 29351595
TI  - Propensity-matched comparison between minimally invasive and conventional
      sternotomy in aortic valve resuspension.
AB  - OBJECTIVES: The aim of the study was to compare the results of David procedure
      through conventional or minimally invasive approach. METHODS: A propensity
      matched comparison in patients undergoing a minimally invasive (partial upper
      sternotomy, n = 103) or complete sternotomy (n = 103) David procedure from 1991
      to 2016 was performed. Patients were 57 +/- 14 years old on average in both
      groups. The David technique was modified by generating a neosinus (P < 0.01) in
      99 (96%) patients (minimally invasive group) and in 42 (41%) patients (complete
      sternotomy group), respectively. The average follow-up time was 3 +/- 2 years
      (minimally invasive group) and 8 +/- 4 years (complete sternotomy group).
      RESULTS: There was only 1 in-hospital death (in the full sternotomy group, P =
      0.5). The applied quantity of packed red blood cells (pRBC) was significantly
      higher in the complete sternotomy group (3.4 +/- 4 vs 1 +/- 0.5, P < 0.01). There
      were no late deaths in the minimally invasive group but 14 died during a longer
      follow-up period in the full sternotomy group (P < 0.01). Freedom from
      reoperation or aortic valve insufficiency >=2 degrees  was 95% vs 93% (minimally
      invasive versus complete sternotomy group) at 5 years and 95% vs 79% at 10 years
      (P < 0.01). CONCLUSIONS: The minimally invasive aortic valve reimplantation
      procedure for selected patients with aortic root aneurysm and aortic valve
      incompetence is a durable procedure with minor valve-related morbidity and
      mortality at the mid-term follow-up. The intra- and perioperative application of
      pRBC was significantly lower in the minimally invasive group. However, comparison
      of long-term follow-up data in both groups is necessary to evaluate valve
      function.

PMID- 29351596
TI  - Freedom Solo(r) versus Trifecta(r) bioprostheses: clinical and haemodynamic
      evaluation after propensity score matching.
AB  - OBJECTIVES: The goal of this study was to compare the stentless Freedom Solo(r)
      (FS) and the stented Trifecta(r) (TF) aortic bioprostheses with regard to
      haemodynamic profile, left ventricular mass regression and early and late
      postoperative outcomes and survival. METHODS: A longitudinal cohort study of
      consecutive patients undergoing aortic valve replacement (2009-16) with either
      the FS or TF at 1 centre was performed. Local databases and national records were
      queried. Prosthesis haemodynamics and left ventricular dimensions were obtained
      from postoperative echocardiograms. After propensity score matching (21
      covariates), the Kaplan-Meier and competing risk analyses were performed for
      survival and the combined outcome of structural valve deterioration and
      endocarditis, respectively. Haemodynamics and mass regression were assessed by a
      mixed-effects model including propensity score as a covariate. RESULTS: From a
      total sample of 397 patients with the FS and 525 TF bioprostheses with a median
      follow-up time of 4.0 (2.2-6.0) and 2.4 (1.4-3.7) years, respectively, a matched
      sample of 329 pairs was obtained. Matched groups showed no differences in
      survival (hazard ratio = 1.04, 95% confidence interval = 0.69-1.56) or cumulative
      hazards of combined outcome (subdistribution hazard ratio = 0.54, 95% confidence
      interval = 0.21-1.39). Although the TF showed an improved haemodynamic profile,
      no difference was found in mass regression. Patients with TF bioprostheses had
      higher rates of prolonged mechanical ventilation, whereas patients with the FS
      bioprosthesis showed higher rates of thrombocytopenia. CONCLUSIONS: The TF showed
      an improved haemodynamic profile compared to the FS, but this did not translate
      into further reverse remodelling. Postoperative outcomes and survival rates were
      comparable for both bioprostheses. Long-term follow-up is needed for comparisons
      with classical bioprosthesis models.

PMID- 29351598
TI  - Smooth muscle cells of intracranial vessels: from development to disease.
AB  - Cerebrovascular diseases that cause ischaemic or haemorrhagic stroke with
      subsequent loss of life or functional capacity due to damage of the brain tissue
      are among the leading causes of human suffering and economic burden inflicted by
      diseases in the developed world. Diseases affecting intracranial vessels are
      significant contributors to ischaemic and haemorrhagic strokes. Brain
      arteriovenous malformations, which are a collection of abnormal blood vessels
      connecting arteries to veins, are the most common cause of intracranial
      haemorrhage in children and young adults. Saccular intracranial aneurysms, which
      are pathological saccular dilations mainly occurring at bifurcations of the large
      intracranial arteries near the circle of Willis, are highly prevalent in the
      middle-aged population, causing significant anxiety and concern; their rupture,
      although rare, is a significant cause of intracranial haemorrhage in those past
      middle age that is associated with a very sinister prognosis. Cerebral small
      vessel disease, which comprise all pathological processes affecting vessels <500
      microns in diameter, account for the majority of intracerebral haemorrhages and
      ~25% of ischaemic strokes and 45% of dementias in the elderly. In this review, we
      summarize the developmental, structural, and functional features of intracranial
      vessels. We then describe the role of smooth muscle cells in brain arteriovenous
      malformations, intracranial aneurysms, and small-vessel diseases, and discuss how
      the peculiar ontogeny, structure, and function of intracranial vessels are
      related to the development of these diseases.

PMID- 29351597
TI  - A systematic review of health promotion interventions to increase breast cancer
      screening uptake: from the last 12 years.
AB  - Background: The outcome of breast cancer treatment largely depends on the timing
      of detection. The health promotion interventions have an immense contribution to
      early detection and improved survival. Therefore, this review aimed to provide
      evidence on the efficacy of the health promotion interventions to increase the
      uptake of breast cancer screening and to develop effective interventions
      targeting women. Methods: Online databases (PubMed/MEDLINE/PubMed Central,
      Ovid/MEDILINE, EMBASE, Web of Science and Google Scholar) were searched for
      studies published between January 2005 and January 2017. A quality coding system
      was assessed using Cochrane checklists for randomized controlled trial (RCT) and
      Downs and Black checklists for non-RCT. The score was rated for the included
      articles by each researcher independently and the average score is given
      accordingly. This study was registered in PROSPERO as [PROSPERO 2017:
      CRD42017060488]. Results: The review dovetailed 22 studies. Thirteen studies
      (59.10%) were conducted in the Unite States, 4 in Iran (18.18%), 2 in India
      (9.09%) and 1 each in Turkey, Saudi Arabia and Israel. The interventions were
      classified as 'individual-based', 'community-based', 'group-based teachings and
      training' and 'behavioral model based'. The majority of the studies showed
      favorable outcomes after health promotion interventions, including improvements
      in women's view of breast screening, breast self-examination and knowledge of
      breast screening. Conclusion: The review confirmed that most of the health
      promotion interventions targeting women boosted the breast screening in one or
      another way. However, the limited quality of the included studies showed that
      further research is needed to improve the trials in the next future.

PMID- 29351599
TI  - ST-segment elevation myocardial infarction caused by aortic pseudoaneurysm
      following surgical mitral valvuloplasty.
AB  - Pseudoaneurysm is one of the complications after arterial cannulation. We report
      the case of a patient with ST-segment elevation myocardial infarction due to
      aortic pseudoaneurysm after surgical mitralvalvuloplasty. Careful evaluation
      should be performed in cases of ST-segment elevation myocardial infarction
      following cardiac surgery, even after several months.

PMID- 29351600
TI  - GTC: how to maintain huge genotype collections in a compressed form.
AB  - Motivation: Nowadays, genome sequencing is frequently used in many research
      centers. In projects, such as the Haplotype Reference Consortium or the Exome
      Aggregation Consortium, huge databases of genotypes in large populations are
      determined. Together with the increasing size of these collections, the need for
      fast and memory frugal ways of representation and searching in them becomes
      crucial. Results: We present GTC (GenoType Compressor), a novel compressed data
      structure for representation of huge collections of genetic variation data. It
      significantly outperforms existing solutions in terms of compression ratio and
      time of answering various types of queries. We show that the largest of publicly
      available database of about 60 000 haplotypes at about 40 million SNPs can be
      stored in <4 GB, while the queries related to variants are answered in a fraction
      of a second. Availability and implementation: GTC can be downloaded from
      https://github.com/refresh-bio/GTC or http://sun.aei.polsl.pl/REFRESH/gtc.
      Contact: sebastian.deorowicz@polsl.pl. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29351601
TI  - What causes health inequality? A systematic review on the relative importance of
      social causation and health selection.

PMID- 29351602
TI  - The integrity and organization of the human AIPL1 functional domains is critical
      for its role as a HSP90-dependent co-chaperone for rod PDE6.

PMID- 29351603
TI  - The unexpected function of a Flavin-dependent oxidoreductase from Variovorax
      paradoxus TBEA6.
AB  - 3,3'-Thiodipropionic acid (TDP) is used as an additive in food and cosmetic
      industry and as precursor substrate for biotechnical polythioester production.
      Its catabolism was investigated in Variovorax paradoxus TBEA6 previous to this
      study. It was reported that the insertion of the transposon Tn5::mob into a gene
      showing high homology to flavin-dependent oxidoreductases (fox) resulted in
      impaired growth with TDP. Therefore, it was assumed that the initial cleavage of
      TDP is catalyzed by an FAD-dependent oxidoreductase (Fox, VPARA_05580).
      Accordingly, fox was heterologously expressed as a thioredoxin fusion protein.
      Analytical size exclusion chromatography revealed a homodimeric structure and the
      presence of the cofactor FAD. In vitro experiments showed that FoxTBEA6 is a D-2
      hydroxy acid specific dehydrogenase and that its activity is enhanced in presence
      of either Ni2+, Co2+ or Zn2+. Cleavage of TDP by FoxTBEA6 was not observed. The
      findings are contrary to restricted growth with TDP of the transposon mutants and
      the previously published deletion mutant V. paradoxus TBEA6 Deltafox. In this
      study, this contradiction was investigated by generation of additional deletion
      mutants, in which partial or complete deletion of fox did not affect utilization
      of TDP, and the mapping of single nucleotide polymorphisms (SNPs) in V. paradoxus
      TBEA6 Deltafox.

PMID- 29351604
TI  - Evaluation of results-based financing in the Republic of the Congo: a comparison
      group pre-post study.
AB  - Results-based financing (RBF) has been advocated and increasingly scaled up in
      low- and middle-income countries to increase utilization and quality of key
      primary care services, thereby reducing maternal and child mortality rates. This
      pilot RBF study in the Republic of the Congo from 2012 to 2014 used a quasi
      experimental research design. The authors conducted pre- and post-household
      surveys and gathered health facility services data from both intervention and
      comparison groups. Using a difference-in-differences approach, the study
      evaluated the impact of RBF on maternal and child health services. The household
      survey found statistically significant improvements in quality of services
      regarding the availability of medicines, perceived quality of care, hygiene of
      health facilities and being respected at the reception desk. The health facility
      survey showed no adverse effects and significantly favourable impacts on:
      curative visits, patient referral, children receiving vitamin A, HIV testing of
      pregnant women and assisted deliveries. These improvements, in relative terms,
      ranged from 42% (assisted deliveries) to 155% (children receiving vitamin A).
      However, the household survey found no statistically significant impacts on the
      five indicators measuring the use of maternal health services, including the
      percentage of pregnant women using prenatal care, 3+ prenatal care, postnatal
      care, assisted delivery, and family planning. Surprisingly, RBF was found to be
      associated with a reduction of coverage of the third diphtheria, pertussis, and
      tetanus immunization among children in the household survey. From the health
      facility survey, no association was found between RBF and full immunization among
      children. Overall, the study shows a favourable impact of an RBF programme on
      most, but not all, targeted maternal and child health services. Several aspects
      of programme implementation, such as timely disbursement of incentives,
      monitoring health facility performance, and transparency of using funds could be
      further strengthened to maximize RBF's impact.

PMID- 29351605
TI  - Association analyses of East Asian individuals and trans-ancestry analyses with
      European individuals reveal new loci associated with cholesterol and triglyceride
      levels.

PMID- 29351606
TI  - Analysis of metal tolerance in Rhizobium leguminosarum strains isolated from an
      ultramafic soil.
AB  - Natural habitats containing high amounts of heavy metals provide a valuable
      source of bacteria adapted to deal with metal toxicity. A functional analysis of
      the population of legume endosymbiotic bacteria in an ultramafic soil was
      undertaken by studying a collection of Rhizobium leguminosarum bv viciae (Rlv)
      isolates obtained using pea as trap plant. One of the isolates, Rlv UPM1137, was
      selected on the basis of its higher tolerance to nickel and cobalt and presence
      of inducible mechanisms for such tolerance. A random transposon mutagenesis of
      Rlv UPM1137 allowed the generation of 14 transposant derivatives with increased
      nickel sensitivity; five of these transposants were also more sensitive to
      cobalt. Sequencing of the insertion sites revealed that one of the transposants
      (D2250) was affected in a gene homologous to the cation diffusion facilitator
      gene dmeF first identified in the metal-resistant bacterium Cupriavidus
      metallidurans CH34. The symbiotic performance of D2250 and two other transposants
      bearing single transposon insertions was unaffected under high-metal conditions,
      suggesting that, in contrast to previous observations in other Rlv strain, metal
      tolerance in UPM1137 under symbiotic conditions might be supported by functional
      redundancy between several mechanisms.

PMID- 29351607
TI  - Sector-wide or disease-specific? Implications of trends in development assistance
      for health for the SDG era.
AB  - The record of the Millennium Development Goals broadly reflects the trade-offs of
      disease-specific financing: substantial progress in particular areas, facilitated
      by time-bound targets that are easy to measure and communicate, which shifted
      attention and resources away from other areas, masked inequalities and
      exacerbated fragmentation. In many ways, the Sustainable Development Goals
      reflect a profound shift towards a more holistic, system-wide approach. To inform
      responses to this shift, this article builds upon existing work on aggregate
      trends in donor financing, bringing together what have largely been disparate
      analyses of sector-wide and disease-specific financing approaches. Looking across
      the last 26 years, the article examines how international donors have allocated
      development assistance for health (DAH) between these two approaches and how
      attempts to bridge them have fared in practice. Since 1990, DAH has
      overwhelmingly favoured disease-specific earmarks over health sector support,
      with the latter peaking in 1998. Attempts to integrate system strengthening
      elements into disease-specific funding mechanisms have varied by disease, and
      more integrated funding platforms have failed to gain traction. Health sector
      support largely remains an unfulfilled promise: proportionately low amounts
      (albeit absolute increases) which have been inconsistently allocated, and the
      overall approach inconsistently applied in practice. Thus, the expansive
      orientation of the Sustainable Development Goals runs counter to trends over the
      last several decades. Financing proposals and efforts to adapt global health
      institutions must acknowledge and account for the persistent challenges in the
      financing and implementation of integrated, cross-sector policies. National and
      subnational experimentation may offer alternatives within and beyond the health
      sector.

PMID- 29351609
TI  - Inequity in contraceptive care between refugees and other migrant women?: a
      retrospective study in Dutch general practice.
AB  - Background: Female refugees are at high risk of reproductive health problems
      including unmet contraceptive needs. In the Netherlands, the general practitioner
      (GP) is the main entrance to the healthcare system and plays a vital role in the
      prescription of contraceptives. Little is known about contraceptive care in
      female refugees in primary care. Objective: To get insight into GP care related
      to contraception in refugees and other migrants compared with native Dutch women.
      Methods: A retrospective descriptive study of patient records of refugees, other
      migrants and native Dutch women was carried out in five general practices in the
      Netherlands. The prevalence of discussions about contraception and prescriptions
      of contraceptives over the past 6 years was compared in women of reproductive age
      (15-49 years). Results: In total, 104 refugees, 58 other migrants and 162 native
      Dutch women were included. GPs in our study (2 male, 3 female) discussed
      contraceptives significantly less often with refugees (51%) and other migrants
      (66%) than with native Dutch women (84%; P < 0.001 and P = 0.004, respectively).
      Contraceptives were less often prescribed to refugees (34%) and other migrants
      (55%) than to native Dutch women (79%; P < 0.001 and P = 0.001). Among refugees
      from Sub-Saharan Africa, contraception was significantly less often discussed
      (28.9%) compared with refugees from other regions (67.8%; P < 0.001). More
      refugees and other migrants had experienced unwanted pregnancies (14%
      respectively 9%) and induced abortions (12% respectively 7%) than native Dutch
      women (4% respectively 4%). Conclusion: Contraceptives were significantly less
      often discussed with and prescribed to refugees and other migrant women compared
      with native Dutch women. More research is needed to elicit the reproductive
      health needs and preferences of migrant women regarding GP's care and experiences
      in discussing these issues. Such insights are vital in order to provide equitable
      reproductive healthcare to every woman regardless of her background.

PMID- 29351608
TI  - Feasibility of drugs in Brugada syndrome: Authors' reply.

PMID- 29351610
TI  - Orthotopic branched endovascular aortic arch repair in patients who cannot
      undergo classical surgery.
AB  - OBJECTIVES: Our goal was to assess the results after orthotopic branched
      endovascular aortic arch repair using a new double-branch endoprosthesis in
      patients with thoracic aortic disease affecting the aortic arch who cannot
      undergo classical surgery. METHODS: Within a 4-year period, 15 patients with
      thoracic aortic disease affecting the aortic arch were treated with the Bolton
      Relay plus double-branch endoprosthesis (Bolton Medical, Sunrise, FL, USA). We
      assessed clinical outcome, occurrence of endoleaks and the need for secondary
      interventions. The median logistic EuroSCORE I level was 13.6 (4.2; 22.8).
      RESULTS: The in-hospital mortality rate was 6.7%. A disabling stroke was observed
      in 1 (6.7%) patient, whereas non-disabling strokes occurred in 2 (13.3%)
      patients. Type I and III endoleaks occurred in 6.7%. The median follow-up period
      was 263 (1st quartile 84; 2nd quartile 564) days. Four patients died during the
      follow-up period. Aortic-related survival was 100%. CONCLUSIONS: Orthotopic
      branched endovascular aortic arch repair using the Bolton Relay Plus double
      branch endoprosthesis is a safe and feasible technique enriching the
      armamentarium to treat patients with thoracic aortic disease who cannot undergo
      classical surgery. Aortic-related survival is excellent, and the occurrence of
      disabling stroke and endoleaks warranting treatment is low. Further studies are
      needed to assess the long-term durability of this new method.

PMID- 29351611
TI  - THE AUTHORS REPLY.

PMID- 29351613
TI  - The beginning at the end: non-invasive assessment of post-transplant coronary
      allograft vasculopathy at the microcirculatory level.

PMID- 29351612
TI  - A mutational signature associated with alcohol consumption and prognostically
      significantly mutated driver genes in esophageal squamous cell carcinoma.
AB  - Background: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at an
      advanced and incurable stage. Information on driver genes and prognosticators in
      ESCC remains incomplete. The objective was to elucidate significantly mutated
      genes (SMGs), mutational signatures, and prognosticators in ESCC. Patients and
      methods: Three MutSig algorithms (i.e. MutSigCV, MutSigCL and MutSigFN) and
      '20/20+' ratio-metric were employed to identify SMGs. Nonnegative matrix
      factorization was used to decipher mutational signatures. Kaplan-Meier survival
      analysis, multivariate Cox and logistic regression models were applied to analyze
      association between mutational features and clinical parameters. Results: We
      identified 26 SMGs, including 8 novel (NAV3, TENM3, PTCH1, TGFBR2, RIPK4, PBRM1,
      USP8 and BAP1) and 18 that have been previously reported. Three mutational
      signatures were identified to be prevalent in ESCC including clocklike C>T at
      CpG, APOBEC overactive C>T at TpCp[A/T], and a signature featured by T>C
      substitution. The T>C mutational signature was significantly correlated with
      alcohol consumption (OR: 3.59; 95% CI: 2.30-5.67; P < 0.001). This alcohol
      consumption signature was also observed in liver cancer and head and neck
      squamous cell carcinoma, and its mutational activity was substantially higher in
      samples with mutations in TP53. Survival analysis revealed that TENM3 mutations
      (HR: 5.54; CI: 2.68-11.45; P < 0.001) and TP53 hotspot mutation p.R213* (HR:
      3.37; CI: 1.73-8.06; P < 0.001) were significantly associated with shortened
      survival outcome. The association remained statistically significant after
      controlling for age, gender, TNM stage and tumor grade. Conclusions: We have
      uncovered several new SMGs in ESCC and defined an alcohol consumption related
      mutational signature. TENM3 mutations and the TP53 hotspot mutation p.R213* are
      independent prognosticators for poor survival in ESCC.

PMID- 29351615
TI  - 18F-fluorodeoxyglucose positron emission/computed tomography and computed
      tomography angiography in prosthetic heart valve endocarditis: from guidelines to
      clinical practice.
AB  - The timely diagnosis of prosthetic heart valve endocarditis remains challenging
      yet of utmost importance. 18F-fluorodeoxyglucose (18 F-FDG) positron
      emission/computed tomography (PET/CT) and cardiac computed tomography angiography
      (CTA) were recently introduced as additional diagnostic tools in the most recent
      ESC guidelines on infective endocarditis. However, how to interpret PET/CT
      findings with regard to what is to be considered abnormal, what the potential
      confounders may be, as well as which patients benefit most from these additional
      imaging techniques and how to best perform them in these often-complex patients,
      remains unclear. This review focusses on factors regarding patient selection and
      image acquisition that need to be taken into account when employing 18F-FDG
      PET/CT and CTA in daily clinical practice, and the importance of a
      multidisciplinary Endocarditis Team herein. Furthermore, it emphasizes the need
      for standardized acquisition protocols and image interpretation, especially now
      that these techniques are starting to be widely embraced by the cardiovascular
      society.

PMID- 29351614
TI  - A Membrane G-Protein-Coupled Estrogen Receptor Is Necessary but Not Sufficient
      for Sex Differences in Zebra Finch Auditory Coding.
AB  - Estradiol acts as a neuromodulator in brain regions important for cognition and
      sensory processing. Estradiol also shapes brain sex differences but rarely have
      these concepts been considered simultaneously. In male and female songbirds,
      estradiol rapidly increases within the auditory forebrain during song exposure
      and enhances local auditory processing. We tested whether G-protein-coupled
      estrogen receptor 1 (GPER1), a membrane-bound estrogen receptor, is necessary and
      sufficient for neuroestrogen regulation of forebrain auditory processing in male
      and female zebra finches (Taeniopygia guttata). At baseline, we observed that
      females had elevated single-neuron responses to songs vs males. In males, narrow
      spiking (NS) neurons were more responsive to conspecific songs than broad-spiking
      (BS) neurons, yet cell types were similarly auditory responsive in females.
      Following acute inactivation of GPER1, auditory responsiveness and coding were
      suppressed in male NS yet unchanged in female NS and in BS of both sexes. By
      contrast, GPER1 activation did not mimic previously established estradiol actions
      in either sex. Lastly, the expression of GPER1 and its coexpression with an
      inhibitory neuron marker were similarly abundant in males and females, confirming
      anatomical similarity in the auditory forebrain. In this study, we found: (1) a
      role for GPER1 in regulating sensory processing and (2) a sex difference in
      auditory processing of complex vocalizations in a cell type-specific manner.
      These results reveal sex specificity of a rapid estrogen signaling mechanism in
      which neuromodulation accounts and/or compensates for brain sex differences,
      dependent on cell type, in brain regions that are anatomically similar in both
      sexes.

PMID- 29351617
TI  - Haemodynamic deterioration due to intra-aortic balloon counterpulsation in
      takotsubo cardiomyopathy.

PMID- 29351616
TI  - Deficient Glucagon Response to Hypoglycemia During a Mixed Meal in Total
      Pancreatectomy/Islet Autotransplantation Recipients.
AB  - Context: Total pancreatectomy and intrahepatic islet autotransplantation (TP/IAT)
      is performed to alleviate severe abdominal pain, avoid narcotic use, maintain
      islet function, and avoid diabetes in patients with chronic pancreatitis.
      However, many TP/IAT recipients complain of postprandial hypoglycemia. Objective:
      This study was designed to discover the mechanisms of this problem. Design:
      Participants consumed a triple-isotope mixed meal. Setting: This study was
      performed in a hospital research unit. Participants: We studied 10 TP/IAT
      recipients and 10 age- and body mass index-matched control subjects. Seven of 10
      recipients had a history of postprandial hypoglycemia. Interventions:
      Participants were given a [1-13C]-labeled mixed meal and two tracer infusions
      ([6,6-2H2]- and [6-3H]-glucose). Main Outcome Measures: Glucose kinetics and
      concentrations of regulatory hormones were determined. Results: Immediately after
      the meal, peak glucose was elevated in recipients compared with control subjects
      [266 +/- 20 mg/dL (14.8 +/- 1.1 mmol/L) vs 185 +/- 13 mg/dL (10.3 +/- 0.7
      mmol/L); P = 0.01]. However, mean Delta glucose for TP/IAT recipients between
      minutes 240 and 360 postprandially was significantly lower than for control
      subjects (P < 0.05); six of the seven recipients with a history of hypoglycemia
      experienced abnormally low postprandial Delta glucose. Delta Glucagon remained
      unchanged (minutes 240 to 360; P = 0.58) in TP/IAT recipients despite abnormal
      decreases in postprandial glucose. Radioisotopic studies revealed that meal
      appearance, glucose disappearance, and endogenous glucose production in TP/IAT
      recipients were not different from control subjects. Conclusion: Initially high
      glucose levels followed by hypoglycemia with an absent glucagon response is a
      mechanistic sequence that contributes to postprandial hypoglycemia after TP/IAT.

PMID- 29351618
TI  - Maintenance hormonal therapy after treatment with medroxyprogesterone acetate for
      patients with atypical polypoid adenomyoma.
AB  - Background: As atypical polypoid adenomyoma (APA) has been reported to be a
      hormone-related tumor, we aimed to analyze the efficacy and safety of maintenance
      hormonal therapy after fertility-preserving treatment of these patients with
      medroxyprogesterone acetate (MPA). Methods: Data were retrospectively analyzed
      from patients with APA who were treated with a fertility-preserving regimen
      including MPA between October 2001 and December 2011. Eighteen patients were
      treated with MPA and 14 (77.8%) achieved either a complete or a partial response
      after the planned treatment. Five patients took progestin for maintenance
      therapy. Results: Eighteen patients were treated for a mean observation period of
      96.7 months. While taking the maintenance therapy, no patient had APA relapse.
      One patient developed well-differentiated endometrioid adenocarcinoma 18 months
      after she stopped taking maintenance progestin. Eleven patients without
      maintenance therapy underwent hysterectomy, andnine of them developed well
      differentiated endometrial cancer. Through univariate analysis, there was a
      significant difference in time to hysterectomy between patients with and without
      maintenance therapy (P = 0.015). Through multivariate analysis, body mass index
      (BMI), menstrual status before protocol therapy, maintenance treatment, and
      pregnancy were found to be significantly associated with a lower risk of
      hysterectomy. No patient had a recurrence of APA after hysterectomy during the
      observation period (median, 54 months; range, 2-148 months). Conclusion: No
      patient showed progression while receiving hormonal therapy, including initial
      protocol therapy. Maintenance hormonal therapy after treatment with MPA was
      highly effective and safe, particularly in patients with BMI ?24 kg/m2 and
      irregular menstruation cycle.

PMID- 29351619
TI  - Repairing folding-defective alpha-sarcoglycan mutants by CFTR correctors, a
      potential therapy for limb-girdle muscular dystrophy 2D.
AB  - Limb-girdle muscular dystrophy type 2D (LGMD2D) is a rare autosomal-recessive
      disease, affecting striated muscle, due to mutation of SGCA, the gene coding for
      alpha-sarcoglycan. Nowadays, more than 50 different SGCA missense mutations have
      been reported. They are supposed to impact folding and trafficking of alpha
      sarcoglycan because the defective polypeptide, although potentially functional,
      is recognized and disposed of by the quality control of the cell. The secondary
      reduction of alpha-sarcoglycan partners, beta-, gamma- and delta-sarcoglycan,
      disrupts a key membrane complex that, associated to dystrophin, contributes to
      assure sarcolemma stability during muscle contraction. The complex deficiency is
      responsible for muscle wasting and the development of a severe form of dystrophy.
      Here, we show that the application of small molecules developed to rescue
      DeltaF508-CFTR trafficking, and known as CFTR correctors, also improved the
      maturation of several alpha-sarcoglycan mutants that were consequently rescued at
      the plasma membrane. Remarkably, in myotubes from a patient with LGMD2D,
      treatment with CFTR correctors induced the proper re-localization of the whole
      sarcoglycan complex, with a consequent reduction of sarcolemma fragility.
      Although the mechanism of action of CFTR correctors on defective alpha
      sarcoglycan needs further investigation, this is the first report showing a
      quantitative and functional recovery of the sarcoglycan-complex in human
      pathologic samples, upon small molecule treatment. It represents the proof of
      principle of a pharmacological strategy that acts on the sarcoglycan maturation
      process and we believe it has a great potential to develop as a cure for most of
      the patients with LGMD2D.

PMID- 29351620
TI  - Correlates of atherosclerotic cardiovascular disease risk in older Colorado
      firefighters.
AB  - Background: It has been documented that cardiovascular disease is the leading
      cause of mortality in on-duty firefighters and little is known about the
      association between cardiorespiratory fitness and 10-year risk of atherosclerotic
      cardiovascular disease (ASCVD). Aims: To estimate the probability of 10-year
      ASCVD risk and its association with per cent body fat (%BF), metabolic syndrome
      (MetS) and physical fitness in Colorado firefighters. Methods: Ten-year ASCVD
      risk was calculated using the newly developed pooled cohort equations in
      firefighters. Logistic regression was conducted to examine the association of 10
      year ASCVD risk (<5 versus >=5%) with estimated maximum volume of oxygen (VO2
      max), %BF and MetS. Results: Out of 294 firefighters, 9% had a 10-year ASCVD risk
      >5%. In the unadjusted models, %BF (odds ratio [OR] = 1.13, P < 0.01), VO2 max
      (OR = 2.87, P < 0.05) and MetS (OR = 2.66, P < 0.05) were significantly
      associated with 10-year ASCVD risk. In the adjusted model, only %BF (OR = 1.17, P
      < 0.01) was significantly associated with 10-year ASCVD risk. Conclusions: Among
      Colorado firefighters, %BF, but not cardiorespiratory fitness, was independently
      associated with 10-year ASCVD.

PMID- 29351622
TI  - Antimicrobial Peptide Resistance Mechanism Contributes to Staphylococcus aureus
      Infection.
AB  - Antimicrobial peptides (AMPs) constitute an important part of innate host
      defense. Possibly limiting the therapeutic potential of AMPs is the fact that
      bacteria have developed AMP resistance mechanisms during their co-evolution with
      humans. However, there is no direct evidence that AMP resistance per se is
      important during an infection. Here we show that the Staphylococcus aureus Pmt
      ABC transporter defends the bacteria from killing by important human AMPs and
      elimination by human neutrophils. By showing that Pmt contributes to virulence
      during skin infection in an AMP-dependent manner, we provide evidence that AMP
      resistance plays a key role in bacterial infection.

PMID- 29351621
TI  - Familial paroxysmal kinesigenic dyskinesia is associated with mutations in the
      KCNA1 gene.

PMID- 29351623
TI  - Development of sugar chain-binding single-chain variable fragment antibody to
      adult T-cell leukemia cells using glyco-nanotechnology and phage display method.
AB  - Adult T-cell leukemia (ATL) is an intractable blood cancer caused by the
      infection of human T-cell leukemia virus type-1, and effective medical treatment
      is required. It is known that the structure and expression levels of cell surface
      sugar chains vary depending on cell states such as inflammation and cancer. Thus,
      it is expected that the antibody specific for ATL cell surface sugar chain would
      be an effective diagnostic tool and a strong candidate for the development of an
      anti-ATL drug. Here, we developed a stable sugar chain-binding single-chain
      variable fragment antibody (scFv) that can bind to ATL cells using a fibre-type
      Sugar Chip and phage display method. The fiber-type Sugar Chips were prepared
      using O-glycans released from ATL cell lines. The scFv-displaying phages derived
      from human B cells (diversity: 1.04 * 108) were then screened using the fiber
      type Sugar Chips, and an O-glycan-binding scFv was obtained. The flow cytometry
      analysis revealed that the scFv predominantly bound to ATL cell lines. The sugar
      chain-binding properties of the scFv was evaluated by array-type Sugar Chip
      immobilized with a library of synthetic glycosaminoglycan disaccharide
      structures. Highly sulphated disaccharide structures were found to have high
      affinity to scFv.

PMID- 29351624
TI  - Takotsubo Cardiomyopathy Associated With Work-Place Bullying.
AB  - Background: Takotsubo cardiomyopathy (TC) is a condition of transient left
      ventricular dysfunction precipitated by acute physical or emotional stress. The
      pathogenesis of TC is not well understood, but it is known to predominantly
      affect postmenopausal women in the context of physical or emotional triggers.
      Aims: To describe a case of TC with an association to a never previously
      described work place stressor of bullying. Case Report: A 48-year-old female
      lawyer developed acute chest pain after experiencing significant emotional
      distress at a workplace meeting. She had experienced 18 months of increasing work
      related mental stress in a new managerial role. She was initially thought to have
      a non-ST-elevation myocardial infarction (NSTEMI) with widespread T wave
      inversion on electrocardiogram and elevated serial troponin. However, a diagnosis
      of TC was subsequently made given the characteristic apical ballooning morphology
      of the left ventricle found on echocardiogram, normal coronary arteries on
      angiography and a normal echocardiogram 3 weeks later. This case report describes
      TC in a younger demographic and a link with workplace bullying. Conclusions:
      Chronic workplace bullying has the potential for serious physical harm by
      precipitating Takotsubo cardiomyopathy.

PMID- 29351625
TI  - Physical activity, weight and functional limitations in elderly Spanish people:
      the National Health Survey (2009-2014).
AB  - Background: The purpose of this study was to analyze physical activity (PA),
      functional limitations, weight status, self-perceived health status and disease
      or chronic health problems in older people aged 65 and over using the European
      Health Survey in Spain (EHSS) conducted one in 2009 and one in 2014. Methods:
      This study included 12,546 older people, 6026 [2330 men and 3696 women; age
      (Mean, SD) =75.61 +/- 7.11 years old] in 2009 and 6520 [2624 men and 3896 women;
      age (Mean, SD) =75.90 +/- 7.59 years old] in 2014. The sample was divided into
      three age groups: 65-74 years old, 75-84 years old and >=85 years old. Results:
      In 2014, participants exhibited lower values for moderate PA, and self-perceived
      health status compared to 2009. Moreover, in 2014 more people with disease or
      chronic health problems, and severe difficulty walking 500 m without assistance
      were found and severe difficulty going up and down 12 stairs than people in 2009.
      In relation to weight status there were no significant differences between older
      people in 2009 and 2014. Conclusions: From 2009 to 2014, the PA levels of Spanish
      older people have decreased, while the BMI has not increased. That fact is in
      consonance with a worst perception of health status in 2014 and with an increase
      of their disease levels. The current data highlight the importance of
      incorporating exercise programmes at an early stage of ageing in order to
      preserve physical performance, and to prevent the negative consequences of
      ageing.

PMID- 29351626
TI  - Neuroendovascular Fellowship Training: Self-Assessment of a Program Accredited by
      the Committee on Advanced Subspecialty Training.
AB  - The University at Buffalo's neuroendovascular fellowship is one of the longest
      running fellowship programs in North America. The burgeoning neurointerventional
      workforce and the rapid growth in the neurointerventional space on the heels of
      groundbreaking clinical trials prompted us to assess the fellowship's academic
      impact and its graduates' perceptions and productivity. An anonymized web-based
      survey was sent to all former neuroendovascular fellows with specific questions
      pertaining to current practice, research and funding, and perceptions about the
      fellowship's impact on their skills, competitiveness, and compensation.
      Additionally, the h-index was calculated to assess the academic productivity of
      each graduated fellow. Among 50 former fellows, 42 (84%) completed the survey.
      The fellows came from various countries, ethnic backgrounds, and specialties
      including neurosurgery (n = 39, 93%), neurology (n = 2, 5%), and neuroradiology
      (n = 1, 2%). Twenty (48%) respondents were currently chairs or directors of their
      practice. Most (n = 30, 71%) spent at least 10% of their time on research
      activities, with 27 (64%) receiving research funding. The median h-index of all
      50 former fellows was 14. The biggest gains from the fellowship were reported to
      be improvement in endovascular skills (median = 10 on a scale of 0-10 [highest])
      and increase in competitiveness for jobs in vascular neurosurgery (median = 10),
      followed by increase in academic productivity (median = 8), and knowledge of
      vascular disease (median = 8). In an era with open calls for moratoriums on
      endovascular fellowships, concerns over market saturation, and pleas to improve
      training, fellowship programs perhaps merit a more objective assessment. The
      effectiveness of a fellowship program may best be measured by the academic impact
      and leadership roles of former fellows.

PMID- 29351628
TI  - 'A new staging system for cardiac transthyretin amyloidosis': is it already on
      the verge of obsolescence?

PMID- 29351629
TI  - Housing conditions and risk of physical function limitations: a prospective study
      of community-dwelling older adults.
AB  - Background: Poor housing conditions have been associated with an increased risk
      of morbidity and mortality in old age. Methods: Prospective cohort of 1602 older
      adults followed from 2012 to 2015. Poor conditions were defined as living in a
      walk-up building, lacking piped hot water or heating, feeling frequently cold at
      home, lacking a bathtub/shower, a refrigerator, a washing machine, an own room or
      a landline. Frailty was assessed with the Fried criteria, lower extremities
      performance with the Short Physical Performance Battery (SPPB), and disability in
      instrumental activities of daily living (IADL) with the Lawton and Brody
      questionnaire. Results: During follow-up, 55 individuals (4.2%) developed frailty
      and 107 (7.2%) IADL disability. Mean (SD) SPPB values at baseline and at follow
      up were 8.5 (2.5) and 8.6 (2.4), respectively. After multivariate adjustment,
      participants who lived in homes with >=1 poor conditions showed a higher risk of
      frailty (odds ratio [OR] = 2.02; 95% confidence interval [95% CI]: 1.09-3.75) and
      transportation disability (OR = 3.50; 95% CI: 1.38-8.88). Lacking heating and
      feeling frequently cold were associated with an increased risk of exhaustion (OR
      = 2.34; 95% CI: 1.00-5.48) and transportation disability (OR = 3.31; 95% CI: 1.07
      10.2), respectively. Conclusions: Prevention programs targeting functional
      limitations in older adults should ensure that they live in suitable housing
      conditions.

PMID- 29351627
TI  - Repair kinetics of DNA double-strand breaks and incidence of apoptosis in mouse
      neural stem/progenitor cells and their differentiated neurons exposed to ionizing
      radiation.
AB  - Neuronal loss leads to neurodegenerative disorders, including Alzheimer's
      disease, Parkinson's disease and Huntington's disease. Because of their long
      lifespans, neurons are assumed to possess highly efficient DNA repair ability and
      to be able to protect themselves from deleterious DNA damage such as DNA double
      strand breaks (DSBs) produced by intrinsic and extrinsic sources. However, it
      remains largely unknown whether the DSB repair ability of neurons is more
      efficient compared with that of other cells. Here, we investigated the repair
      kinetics of X-ray-induced DSBs in mouse neural cells by scoring the number of
      phosphorylated 53BP1 foci post irradiation. We found that p53-independent
      apoptosis was induced time dependently during differentiation from neural
      stem/progenitor cells (NSPCs) into neurons in culture for 48 h. DSB repair in
      neurons differentiated from NSPCs in culture was faster than that in mouse
      embryonic fibroblasts (MEFs), possibly due to the higher DNA-dependent protein
      kinase activity, but it was similar to that in NSPCs. Further, the incidence of
      p53-dependent apoptosis induced by X-irradiation in neurons was significantly
      higher than that in NSPCs. This difference in response of X-ray-induced apoptosis
      between neurons and NSPCs may reflect a difference in the fidelity of non
      homologous end joining or a differential sensitivity to DNA damage other than
      DSBs.

PMID- 29351630
TI  - Prevalence and trends of transfusion-transmittable infections among blood donors
      in Southwest China.
AB  - Background: The high prevalence of transfusion-transmitted infections (TTIs) is
      causing serious harm to human health worldwide. The aim of this research was to
      assess the prevalence and influencing factors of TTIs in Southwest China.
      Methods: A retrospective study of blood donor records from January 2008 to
      December 2015 was conducted. All samples were screened for HBV, HCV, HIV and
      syphilis. The donor's data was recorded and analyzed statistically using SPSS
      software. Results: We revealed that the prevalence of TTIs showed a decreasing
      trend from 2.39 to 1.98%, and this was slightly lower than that in other regions
      of China. Syphilis infection was the most serious issue among blood donors in
      Southwest China, which demonstrated a significantly higher rate than that in
      other areas of China. The high infection rate of the female and farmer groups in
      rural regions is worth noting. The logistic regression model showed that age,
      occupation and donor category was the influential factors for TTIs. Conclusions:
      The overall prevalence of TTIs demonstrated a decreasing trend from 2008 to 2015
      in Southwest China, but there is still a sufficient threat to blood safety, and
      more efforts are needed to further guarantee blood safety in China.

PMID- 29351631
TI  - Atypical radiological presentation of pulmonary invasion of diffuse large B-cell
      lymphoma mimicking Pneumocystis jiroveci pneumonia.

PMID- 29351632
TI  - Presenteeism in academic employees-occupational and individual factors.
AB  - Background: There is growing evidence that presenteeism can be damaging for
      individuals and organizations. It is, therefore, important to identify the
      prevalence of working while sick in different working environments and the
      factors that contribute to such behaviour. Aims: To examine the prevalence of
      self-reported presenteeism in academic staff working in UK universities and
      colleges and the extent to which job demands, control, support and work
      engagement are risk factors. Methods: Scales from the Health and Safety Executive
      Management Standards Indicator Tool were used to measure job demands, control and
      support from managers and co-workers. Work engagement was assessed using a
      validated measure and the frequency of self-reported presenteeism was measured.
      The effects of demands, control, support and engagement on presenteeism were
      examined with ordinal regression analysis. Results: The study sample comprised
      6874 people working in academic roles in UK colleges and universities (59%
      female). Most respondents (88%) reported working while sick at least sometimes.
      The risk factors for presenteeism were job demands, control, support from
      managers and work engagement. Conclusions: The findings of this study indicate
      that presenteeism is commonplace in UK colleges and universities. Some of the
      features of the job that might encourage employees to work while sick are
      highlighted, whereas engagement in work was an additional risk factor.

PMID- 29351634
TI  - Commentary: How Should Hospitals Respond to Surgeons' Requests to Schedule
      Overlapping Surgeries?

PMID- 29351633
TI  - Evolutionary Genetics of Cytoplasmic Incompatibility Genes cifA and cifB in
      Prophage WO of Wolbachia.
AB  - The bacterial endosymbiont Wolbachia manipulates arthropod reproduction to
      facilitate its maternal spread through host populations. The most common
      manipulation is cytoplasmic incompatibility (CI): Wolbachia-infected males
      produce modified sperm that cause embryonic mortality, unless rescued by embryos
      harboring the same Wolbachia. The genes underlying CI, cifA and cifB, were
      recently identified in the eukaryotic association module of Wolbachia's prophage
      WO. Here, we use transcriptomic and genomic approaches to address three important
      evolutionary facets of the cif genes. First, we assess whether or not cifA and
      cifB comprise a classic toxin-antitoxin operon in wMel and show that the two
      genes exhibit striking, transcriptional differences across host development. They
      can produce a bicistronic message despite a predicted hairpin termination element
      in their intergenic region. Second, cifA and cifB strongly coevolve across the
      diversity of phage WO. Third, we provide new domain and functional predictions
      across homologs within Wolbachia, and show that amino acid sequences vary
      substantially across the genus. Finally, we investigate conservation of cifA and
      cifB and find frequent degradation and loss of the genes in strains that no
      longer induce CI. Taken together, we demonstrate that cifA and cifB exhibit
      complex transcriptional regulation in wMel, provide functional annotations that
      broaden the potential mechanisms of CI induction, and report recurrent erosion of
      cifA and cifB in non-CI strains, thus expanding our understanding of the most
      widespread form of reproductive parasitism.

PMID- 29351635
TI  - Reversibility of severe mitral valve regurgitation after left ventricular assist
      device implantation: single-centre observations from a real-life population of
      patients.
AB  - OBJECTIVES: This study evaluates the impact of untreated preoperative severe
      mitral valve regurgitation (MR) on outcomes after left ventricular assist device
      (LVAD) implantation. METHODS: Of the 234 patients who received LVAD therapy in
      our centre during a 6-year period, we selected those who had echocardiographic
      images of good quality and excluded those who underwent mitral valve replacement
      prior to or mitral valve repair during LVAD placement. The 128 patients selected
      were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none
      to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic
      echocardiography preoperatively [15 (7-28) days before LVAD implantation; median
      (interquartile range)] and postoperatively up to the last available follow-up
      [501 (283-848) days after LVAD]. We collected mortality, complications and
      clinical status indicators of the patient cohort. RESULTS: We observed a
      significant decrease in the severity of MR after LVAD implantation (severe MR 51%
      pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between
      groups in terms of right heart failure, rate of urgent heart transplantation,
      pump thrombosis or ventricular arrhythmias. There was no difference in 1-year
      survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and
      B, respectively, P = 0.97). CONCLUSIONS: Preoperative severe MR resolves in the
      majority of patients early on after LVAD implantation and is not associated with
      worse clinical outcomes or intermediate-term survival.

PMID- 29351636
TI  - Effectiveness of Respiratory Syncytial Virus Immunoprophylaxis in Reducing
      Bronchiolitis Hospitalizations Among High-Risk Infants.
AB  - We sought to determine the real-world effectiveness of respiratory syncytial
      virus (RSV) immunoprophylaxis in a population-based cohort to inform policy. The
      study population included infants born during 1996-2008 and enrolled in the
      Kaiser Permanente Northern California integrated health-care delivery system.
      During the RSV season (November-March), the date of RSV immunoprophylaxis
      administration and the following 30 days were defined as RSV immunoprophylaxis
      protected period(s), and all other days were defined as unprotected period(s).
      Numbers of bronchiolitis hospitalizations were determined using International
      Classification of Diseases, Ninth Revision, codes during RSV season. We used a
      proportional hazards model to estimate risk of bronchiolitis hospitalization when
      comparing infants' protected period(s) with unprotected period(s). Infants who
      had ever received RSV immunoprophylaxis had a 32% decreased risk of bronchiolitis
      hospitalization (adjusted hazard ratio = 0.68, 95% confidence interval: 0.46,
      1.00) when protected periods were compared with unprotected periods. Infants with
      chronic lung disease (CLD) had a 52% decreased risk of bronchiolitis
      hospitalization (adjusted hazard ratio = 0.48, 95% confidence interval: 0.25,
      0.94) when protected periods were compared with unprotected periods. Under the
      new 2014 American Academy of Pediatrics (AAP) guidelines, 48% of infants eligible
      for RSV immunoprophylaxis on the basis of AAP guidelines in place at birth would
      no longer be eligible, but nearly all infants with CLD would remain eligible. RSV
      immunoprophylaxis is effective in decreasing hospitalization. This association is
      greatest for infants with CLD, a group still recommended for receipt of RSV
      immunoprophylaxis under the new AAP guidelines.

PMID- 29351637
TI  - Prospective Multicenter Assessment of All-Cause Mortality Following Surgery for
      Adult Cervical Deformity.
AB  - BACKGROUND: Surgical treatments for adult cervical spinal deformity (ACSD) are
      often complex and have high complication rates. OBJECTIVE: To assess all-cause
      mortality following ACSD surgery. METHODS: ACSD patients presenting for surgical
      treatment were identified from a prospectively collected multicenter database.
      Clinical and surgical parameters and all-cause mortality were assessed. RESULTS:
      Of 123 ACSD patients, 120 (98%) had complete baseline data (mean age, 60.6 yr).
      The mean number of comorbidities per patient was 1.80, and 80% had at least 1
      comorbidity. Surgical approaches included anterior only (15.8%), posterior only
      (50.0%), and combined anterior/posterior (34.2%). The mean number of vertebral
      levels fused was 8.0 (standard deviation [SD] = 4.5), and 23.3% had a 3-column
      osteotomy. Death was reported for 11 (9.2%) patients at a mean of 1.1 yr (SD =
      0.76 yr; range = 7 d to 2 yr). Mean follow-up for living patients was 1.2 yr (SD
      = 0.64 yr). Causes of death included myocardial infarction (n = 2),
      pneumonia/cardiopulmonary failure (n = 2), sepsis (n = 1), obstructive sleep
      apnea/narcotics (n = 1), subsequently diagnosed amyotrophic lateral sclerosis (n
      = 1), burn injury related to home supplemental oxygen (n = 1), and unknown (n =
      3). Deceased patients did not significantly differ from alive patients based on
      demographic, clinical, or surgical parameters assessed, except for a higher major
      complication rate (excluding mortality; 63.6% vs 22.0%, P = .006). CONCLUSION:
      All-cause mortality at a mean of 1.2 yr following surgery for ACSD was 9.2% in
      this prospective multicenter series. Causes of death were reflective of the
      overall high level of comorbidities. These findings may prove useful for
      treatment decision making and patient counseling in the context of the
      substantial impact of ACSD.

PMID- 29351638
TI  - A rare case of granulomatosis with polyangiitis-induced burnout cardiomyopathy:
      role of combined viability and metabolic imaging.

PMID- 29351639
TI  - Call to Action: Prevention of Mother-to-Child Transmission of Hepatitis B in
      Africa.
AB  - Hepatitis B virus (HBV) is a significant public health issue that has not been
      adequately addressed, especially in the high-prevalence region of Africa. Despite
      the incorporation of HBV vaccines into the Expanded Program on Immunization,
      children continue to be infected with HBV through maternal-to-child transmission
      (MTCT). The addition of a birth dose of HBV vaccine would be a cost-effective
      method to reduce MTCT. Birth-dose HBV vaccine policies have been adopted in the
      Western Pacific region but not yet in Africa. Even better protection against HBV
      MTCT can be achieved by treatment of pregnant women with high HBV viral loads
      with tenofovir. Tenofovir is already widely used in prevention of HIV MTCT
      (PMTCT) programs. We suggest that existing HIV PMTCT programs could be expanded
      to deliver care for HBV-infected pregnant women. With appropriate adoption of
      birth-dose vaccination policies and expansion of PMTCT programs, elimination of
      HBV MTCT in Africa is achievable.

PMID- 29351640
TI  - Emergency fast Bentall operation.
AB  - We herein report an emergency technique of composite Bentall operation using a
      fast release valve. The technique was successfully performed in 2 emergency cases
      after failed supracoronary ascending aortic replacement in acute Type A aortic
      dissection. The speed and ease of execution are the main advantages of the
      procedure.

PMID- 29351641
TI  - RE: "INVITED COMMENTARY: EXPOSURE BIOMARKERS INDICATE MORE THAN JUST EXPOSURE".

PMID- 29351642
TI  - Caregiver-Provided Physical Therapy Home Programs for Children with Motor Delay:
      A Scoping Review.
AB  - Background: Caregiver-provided physical therapy home programs (PTHP) play an
      important role in enhancing motor outcomes in pediatric patient populations.
      Purpose: This scoping review systematically mapped clinical trials of caregiver
      provided PTHP that were aimed at enhancing motor outcomes in children who have or
      who are at risk for motor delay, with the purpose of (1) describing trial
      characteristics; (2) assessing methodologic quality; and (3) examining the
      reporting of caregiver-related components. Data Sources: Physiotherapy Evidence
      Database (PEDro), Cochrane CENTRAL, PubMed, Scopus, ScienceDirect, ProQuest
      Central, CINAHL, LILACS, and OTseeker were searched up to July 31, 2017. Study
      Selection: Two reviewers independently assessed study eligibility. Randomized or
      quasi-randomized controlled trials on PTHP administered by parents, other family
      members, friends, or informal caregivers to children who had or who were at risk
      for motor delay were included. Data Extraction: Two reviewers independently
      appraised trial quality on the PEDro scale and extracted data. Data Synthesis:
      Twenty-four articles representing 17 individual trials were identified.
      Populations and interventions investigated were heterogeneous. Most of the trials
      had important research design limitations and methodological issues that could
      limit usefulness in ascertaining the effectiveness of caregiver-provided PTHP.
      Few (4 of 17) trials indicated involvement of caregivers in the PTHP planning,
      assessed how the caregivers learned from the training or instructions provided,
      or carried out both. Limitations: Included studies were heterogeneous, and
      unpublished data were excluded. Conclusions: Although caregiver-provided PTHP are
      important in addressing motor outcomes in this population, there is a lack of
      evidence at the level of clinical trials to guide practice. More research is
      urgently needed to determine the effectiveness of care-giver-provided PTHP.
      Future studies should address the many important issues identified in this
      scoping review to improve the usefulness of the trial results.

PMID- 29351643
TI  - Genetic dissection of the fuzzless seed trait in Gossypium barbadense.
AB  - Cotton fibres are single-celled trichomes arising from the epidermal cells of the
      seed coat and may be either long (lint) or very short (fuzz). The dominant
      fuzzless N1 of Gossypium hirsutum is a defective allele of the At-subgenome
      homoeolog of MYB25-like, but the genetic components underlying the recessive
      fuzzless trait from G. barbadense (Gb) are unknown. We have identified five
      genetic loci, including a major contributing locus containing MYB25-like_Dt,
      associated with Gb fuzzless seeds based on genotyping of fuzzy and fuzzless near
      isogenic lines (NILs) from an interspecies cross (G. barbadense * G. hirsutum).
      At 3 d post-anthesis when fuzz fibres are initiating, expression of MYB25-like_Dt
      was significantly lower in fuzzless NILs than in fuzzy seeded NILs, while higher
      MYB25-like_Dt expression was associated with more seed fuzz across different
      cotton genotypes. Phenotypic and genotypic analysis of MYB25-like homoeoalleles
      in cottons showing different fibre phenotypes and their crossing progeny
      indicated that both MYB25-like_At and MYB25-like_Dt are associated with lint
      development, and that fuzz development is mainly determined by the expression
      level of MYB25-like_Dt at ~3 d post-anthesis. Expression of Gb fuzzless seeds
      depends on genetic background and interactions amongst the multiple loci
      identified. MYB25-like_Dt is one of the best candidates for N2.

PMID- 29351644
TI  - The role of skeletal muscle in the pathophysiology and management of knee
      osteoarthritis.
AB  - The role of skeletal muscle in the pathophysiology of knee OA is poorly
      understood. To date, the majority of literature has focused on the association of
      muscle strength with OA symptoms, disease onset and progression. However,
      deficits or improvements in skeletal muscle strength do not fully explain the
      mechanisms behind outcome measures in knee OA, such as pain, function and
      structural disease. This review aims to summarize components of skeletal muscle,
      providing a holistic view of skeletal muscle mechanisms that includes muscle
      function, quality and composition and their interactions. Similarly, the role of
      skeletal muscle in the management of knee OA will be discussed.

PMID- 29351645
TI  - DOSIMETRY DURING PERCUTANEOUS CORONARY INTERVENTIONS OF CHRONIC TOTAL OCCLUSIONS.
AB  - Percutaneous coronary interventions (PCI) of coronary chronic total occlusions
      (CTO) increase the risk of high radiation exposure for both the patient and the
      cardiologist. This study evaluated the maximum dose to the patients' skin (MSD)
      and the exposure of the cardiologists during CTO-PCI. Moreover, the efficiency of
      radioprotective drapes to reduce cardiologist exposure was assessed. Patient dose
      was measured during 31 procedures; dose to the cardiologist's extremities were
      measured during 65 procedures, among which 31 were performed with radioprotective
      drapes. The MSD was high (median: 1254 mGy; max: 6528 mGy), and higher than 2 Gy
      for 33% of the patients. The dose to the cardiologists' extremities per procedure
      was also of concern (median: 25-465 MUSv), particularly to the left eye (median:
      68 MUSv; max: 187 MUSv). Radioprotective drapes reduced the exposure to
      physician's upper limbs and eyes; especially to the left side (from -28 to -49%).

PMID- 29351646
TI  - Effect of a Postpartum Training Program on the Prevalence of Diastasis Recti
      Abdominis in Postpartum Primiparous Women: A Randomized Controlled Trial.
AB  - Background: Diastasis recti abdominis affects a significant number of women
      during the prenatal and postnatal period. Objective: The objective was to
      evaluate the effect of a postpartum training program on the prevalence of
      diastasis recti abdominis. Design: The design was a secondary analysis of an
      assessor-masked randomized controlled trial. Methods: One hundred seventy-five
      primiparous women (mean age = 29.8 +/- 4.1 years) were randomized to an exercise
      or control group. The interrectus distance was palpated using finger widths, with
      a cutoff point for diastasis as >=2 finger widths. Measures were taken 4.5 cm
      above, at, and 4.5 cm below the umbilicus. The 4-month intervention started 6
      weeks postpartum and consisted of a weekly, supervised exercise class focusing on
      strength training of the pelvic floor muscles. In addition, the women were asked
      to perform daily pelvic floor muscle training at home. The control group received
      no intervention. Analyses were based on intention to treat. The Mantel-Haenszel
      test (relative risk [RR] ratio) and the chi-square test for independence were
      used to evaluate between-group differences on categorical data. Results: At 6
      weeks postpartum, 55.2% and 54.5% of the participants were diagnosed with
      diastasis in the intervention and control groups, respectively. No significant
      differences between groups in prevalence were found at baseline (RR: 1.01 [0.77
      1.32]), at 6 months postpartum (RR: 0.99 [0.71-1.38]), or at 12 months postpartum
      (RR: 1.04 [0.73-1.49]). Limitations: The interrecti distance was palpated using
      finger widths, and the sample included women with and without diastasis.
      Conclusions: A weekly, postpartum, supervised exercise program, including
      strength training of the pelvic floor and abdominal muscles, in addition to daily
      home training of the pelvic floor muscles, did not reduce the prevalence of
      diastasis.

PMID- 29351647
TI  - Minimally Invasive Lateral Retroperitoneal Approach for Resection of
      Extraforaminal Lumbar Plexus Schwannomas: Operative Techniques and Literature
      Review.
AB  - BACKGROUND: Traditional approaches for retroperitoneal lumbar plexus schwannomas
      involve anterior open or laparoscopic resection. For select tumors, the lateral
      retroperitoneal approach provides a minimally invasive alternative. OBJECTIVE: To
      describe a minimally invasive lateral transpsoas approach for the resection of
      retroperitoneal schwannomas. METHODS: A lateral retroperitoneal transpsoas
      approach was used to resect a 3.1 * 2.7 * 4.1 cm schwannoma embedded within the
      psoas muscle. A minimally invasive retractor system allows for appropriate
      visualization and complete resection with the aid of the microscope. The patient
      tolerated the procedure without complication and was discharged on postoperative
      day 2 in good condition at her neurological baseline. RESULTS: The lateral
      retroperitoneal approach provides a minimally invasive alternative for select
      retroperitoneal schwannomas. In theory, this procedure allows for faster recovery
      and less blood loss compared to traditional open anterior approaches. For a
      subset of tumors, anterior laparoscopy may provide better access, but the lateral
      approach is well known to most neurosurgeons who perform lateral interbody
      fusions and can be easily tailored to extraforaminal tumor resection. CONCLUSION:
      Retroperitoneal schwannomas pose a challenge due to their deep location. The
      lateral retroperitoneal approach provides a useful alternative for resection of a
      subset of retroperitoneal schwannomas.

PMID- 29351648
TI  - Transarterial Onyx Embolization of Intracranial Dural Fistulas: A Prospective
      Cohort, Systematic Review, and Meta-Analysis.
AB  - BACKGROUND: Onyx is important embolic material in the endovascular treatment of
      intracranial dural arteriovenous fistula (DAVF). However, its impact on DAVF
      occlusion rates, morbidity, mortality, and complication rates is not fully
      examined. OBJECTIVE: To improve understanding of safety and effectiveness
      profiles associated with transarterial endovascular treatment using Onyx for
      intracranial DAVF. METHODS: We analyzed data from our prospective clinical
      registry and conducted a systematic review of all previous transarterial
      embolization studies using Onyx published between January 2005 and December 2015
      in MEDLINE and EMBASE. RESULTS: In the prospective study, 41 transarterial
      procedures were performed in 33 consecutive patients harboring 36 DAVFs. Complete
      initial exclusion was obtained in 32 of 36 (88.9%) fistulas; 31 fistulas were
      followed up showing 4 (12.9%) recurrences. Procedure-related morbidity and
      mortality were 3% and 0%, respectively. The literature review identified 19
      studies involving a total of 425 patients with 463 DAVFs. Meta-analysis,
      including our registry data, showed an initial complete occlusion rate of 82%
      (95% confidence interval [CI]: 74%, 88%; I2, 70.6%), and recurrence rate at
      midterm of 2% (95% CI: 0%, 5%; I2, 21.5%). Pooled postoperative neurological
      deficit, procedure-related morbidity, and mortality rates were 4% (95% CI: 2%,
      6%; I2, 0%), 3% (95% CI: 1%, 5%; I2, 0%), and 0%, respectively. CONCLUSION: This
      meta-analysis suggests that transarterial embolization with Onyx is a safe
      treatment modality for DAVFs. Although Onyx showed a low recurrence rate at
      midterm, the long-term risk is poorly addressed in our study and should warrant a
      longer follow-up.

PMID- 29351649
TI  - Sex-dependent interactions between leptin, wasting and humoral immunity in two
      ethnic communities of school-aged children differentially exposed to Schistosoma
      haematobium.
AB  - Background: Leptin is a nutritional hormone whose production is generally higher
      in females. We investigated how leptin is associated with sex dimorphism during
      urinary schistosomiasis in relation with wasting. Methods: A cross-sectional
      study was carried out in three villages in northern Senegal. Ninety-eight school
      aged children belonging to the Fulani or Wolof villages were enrolled. We
      performed parasitic diagnosis and anthropometric measurement to evaluate
      nutritional status. We collected peripheral blood to determine the amount of
      circulating leptin and immunoglobulin G (IgG), IgG4 and IgE directed to soluble
      worm antigen preparation (SWAP). Results: The prevalence of Schistosoma
      haematobium infection was higher among boys regardless of ethnic group, but
      exposure to parasites did not exacerbate malnutrition. The greater ability of
      girls to produce leptin was not altered by schistosomiasis and was recovered in
      both ethnic groups. However, while the usual correlation between leptin and fat
      storage was preserved in Fulani girls, it was disrupted in Fulani boys, who
      displayed a remarkable susceptibility for wasting. Finally, we observed that
      leptin was negatively associated with the level of antibodies in Wolof boys.
      Conclusions: Leptin can be disconnected from body fat and may exert a sex
      dependent influence on host immune response to S. haematobium infection in
      Senegalese children.

PMID- 29351650
TI  - Are evidence-based, community-engaged energy balance interventions enough for
      extremely vulnerable populations?
AB  - Well-documented associations between lifestyle behaviors and disease outcomes
      necessitate evidence-based health promotion interventions. To enhance potential
      efficacy and effectiveness, interventionists increasingly respond to community
      priorities, employ comprehensive theoretical frameworks, invest heavily to ensure
      cultural fit, implement evidence-based programming, and deploy research gold
      standards. We describe a project that followed all of these recommended
      strategies, but did not achieve desired outcomes. This community-based
      participatory research (CBPR) energy balance (diet and physical activity)
      intervention, conducted in Appalachian Kentucky among 900+ residents, employed a
      wait list control cluster randomized design. We engaged faith institutions, took
      an intergenerational approach, and modified two existing evidence-based
      interventions to enhance cultural relevance. Despite these efforts, fruit and
      vegetable consumption and physical activity did not change from baseline to post
      test or differed significantly between intervention and wait list control groups.
      Barriers to engaging in optimal energy balance focused more on motivation and
      attitude than on structural and material barriers. The complex interplay of
      psychosocial, structural, and physiological processes offers significant
      challenges to groups with entrenched health challenges.

PMID- 29351651
TI  - RADIOTHERAPY PROTON BEAM PROFILOMETRY WITH scCVD DIAMOND DETECTOR IN SINGLE
      PARTICLE MODE.
AB  - Proton radiotherapy requires precise knowledge of the volumetric dose
      distribution. In proton beam delivery systems, based on narrow pencil beams, a
      contribution from small doses in low-intensity regions, consisting mainly of
      scattered protons, may have not negligible influence on total dose delivered to
      patient. Insufficient information about dose profile can cause underestimation of
      dose and potential delivery of inflated dose during hadrontherapy treatment.
      Presented work aims to verify applicability of diamond detectors, produced by
      Chemical Vapor Deposition method, for therapeutic proton beam profilometry at
      large fields. This requires the capability of measuring the core of the beam
      intensity profile (wide dynamic range) as well as its lateral spread (very high
      sensitivity) with a single device.

PMID- 29351652
TI  - Early Results in Flow Diverter Sizing by Computational Simulation: Quantification
      of Size Change and Simulation Error Assessment.
AB  - BACKGROUND: Sizing of flow diverters (FDs) stent in the treatment of intracranial
      aneurysms is a challenging task due to the change of stent length after
      implantation. OBJECTIVE: To quantify the size change and assess the error in
      length prediction in 82 simulated FD deployments. METHODS: Eighty-two consecutive
      patients treated with FDs were retrospectively analyzed. Implanted FD length was
      measured from angiographic images and compared to the nominal sizes of the
      implanted device. Length change was obtained by subtracting the nominal length
      from the real length and dividing by the nominal length. Implanted devices were
      simulated on 3-dimensional models of each patient. Simulation error was obtained
      by subtracting real length from simulated length and dividing by the real length
      of the FD. Subanalysis was done using ANOVA. Statistical significance was set to
      P < .05, and bootstrap resampling was used. RESULTS: When assessing the length
      change of the FD after implantation, changes of 30% in average and up to 80% with
      reference to the nominal length of the device were observed. The simulation
      results showed a lower error of 3.52% in average with a maximum of 30%. Paired t
      test showed nonsignificant differences between measured and real length (P = .07,
      with the mean of differences at 0.45 mm, 95% confidence interval [-0.950 0.038]).
      CONCLUSION: Nominal length is not an accurate sizing metric when choosing the
      size of an FD irrespective of the brand and manufacturer. Good estimation of the
      final length of the stent after deployment as expressed by an error of 3.5% in
      average.

PMID- 29351653
TI  - CALIBRATION OF GAFCHROMIC EBT3 FILM FOR DOSIMETRY OF SCANNING PROTON PENCIL BEAM
      (PBS).
AB  - Gafchromic EBT3 films are applied in proton radiotherapy for 2D dose mapping
      because they demonstrate spatial resolution well below 1 mm. However, the film
      response must be corrected in order to reach the accuracy of dose measurements
      required for the clinical use. The in-house developed AnalyseGafchromic software
      allows to analyze and correct the measured response using triple channel dose
      calibration, statistical scan-to-scan fluctuations as well as experimentally
      determined dose and LET dependence. Finally, the optimized protocol for
      evaluation of response of Gafchromic EBT3 films was applied to determine 30 * 40
      cm2 dose profiles of the scanning therapy unit at the Cyclotron Centre Bronowice,
      CCB in Krakow, Poland.

PMID- 29351654
TI  - What is the role of imaging in the clinical diagnosis of osteoarthritis and
      disease management?
AB  - While OA is predominantly diagnosed on the basis of clinical criteria, imaging
      may aid with differential diagnosis in clinically suspected cases. While plain
      radiographs are traditionally the first choice of imaging modality, MRI and US
      also have a valuable role in assessing multiple pathologic features of OA,
      although each has particular advantages and disadvantages. Although modern
      imaging modalities provide the capability to detect a wide range of osseous and
      soft tissue (cartilage, menisci, ligaments, synovitis, effusion) OA-related
      structural damage, this extra information has not yet favourably influenced the
      clinical decision-making and management process. Imaging is recommended if there
      are unexpected rapid changes in clinical outcomes to determine whether it relates
      to disease severity or an additional diagnosis. On developing specific
      treatments, imaging serves as a sensitive tool to measure treatment response.
      This narrative review aims to describe the role of imaging modalities to aid in
      OA diagnosis, disease progression and management. It also provides insight into
      the use of these modalities in finding targeted treatment strategies in clinical
      research.

PMID- 29351655
TI  - ESTABLISHING DIAGNOSTIC REFERENCE LEVELS FOR CARDIAC COMPUTED TOMOGRAPHY
      ANGIOGRAPHY IN SAUDI ARABIA.
AB  - Cardiac computed tomography angiography (CCTA) is a commonly used diagnostic
      imaging tool for cardiovascular disease. Despite constant improvements to imaging
      technologies, the radiation dose to patients remains a concern when using this
      procedure. Diagnostic reference levels (DRLs) are used as a trigger to identify
      and alert individual facilities that are using high doses during CT. This study
      aims to assess patient radiation dose and establish new national DRLs (NDRL)
      associated with CCTA in Saudi clinical practices. A structured booklet survey was
      designed for recording patient and scanning protocols during CCTA procedures. The
      data were collected retrospectively from the participating centres. NDRLs for
      CCTA were defined as the 75th and 25th of volumetric CT dose index (CTDIvol) and
      dose length product (DLP). Specific DRLs based on two main ECG-gating modes were
      also proposed. Data sets related to 197 CCTAs with a mean weight of 77 kg were
      analysed in detail. The DRL values for CTDIvol and DLP for prospective gating
      mode and retrospective gating mode were 29 and 62 mGy and 393 and 1057 mGy cm,
      respectively. NDRLs for CCTA in Saudi Arabia are comparable or slightly lower
      than European DRLs due to the current use of dose-saving technology. There are
      major variations in patient doses during CCTA due to differences in CT scanners,
      scanning modes and departmental CCTA protocols.

PMID- 29351656
TI  - Evaluation of a new neutron energy spectrum unfolding code based on an Adaptive
      Neuro-Fuzzy Inference System (ANFIS).
AB  - The purpose of the present study was to reconstruct the energy spectrum of a poly
      energetic neutron source using an algorithm developed based on an Adaptive Neuro
      Fuzzy Inference System (ANFIS). ANFIS is a kind of artificial neural network
      based on the Takagi-Sugeno fuzzy inference system. The ANFIS algorithm uses the
      advantages of both fuzzy inference systems and artificial neural networks to
      improve the effectiveness of algorithms in various applications such as modeling,
      control and classification. The neutron pulse height distributions used as input
      data in the training procedure for the ANFIS algorithm were obtained from the
      simulations performed by MCNPX-ESUT computational code (MCNPX-Energy engineering
      of Sharif University of Technology). Taking into account the normalization
      condition of each energy spectrum, 4300 neutron energy spectra were generated
      randomly. (The value in each bin was generated randomly, and finally a
      normalization of each generated energy spectrum was performed). The randomly
      generated neutron energy spectra were considered as output data of the developed
      ANFIS computational code in the training step. To calculate the neutron energy
      spectrum using conventional methods, an inverse problem with an approximately
      singular response matrix (with the determinant of the matrix close to zero)
      should be solved. The solution of the inverse problem using the conventional
      methods unfold neutron energy spectrum with low accuracy. Application of the
      iterative algorithms in the solution of such a problem, or utilizing the
      intelligent algorithms (in which there is no need to solve the problem), is
      usually preferred for unfolding of the energy spectrum. Therefore, the main
      reason for development of intelligent algorithms like ANFIS for unfolding of
      neutron energy spectra is to avoid solving the inverse problem. In the present
      study, the unfolded neutron energy spectra of 252Cf and 241Am-9Be neutron sources
      using the developed computational code were found to have excellent agreement
      with the reference data. Also, the unfolded energy spectra of the neutron sources
      as obtained using ANFIS were more accurate than the results reported from
      calculations performed using artificial neural networks in previously published
      papers.

PMID- 29351657
TI  - Characterization of the Spatial and Temporal Distribution of Nipah Virus
      Spillover Events in Bangladesh, 2007-2013.
AB  - Nipah virus is a zoonotic virus harbored by bats and lethal to humans. Bat-to
      human spillovers occur every winter in Bangladesh. However, there is significant
      heterogeneity in the number of spillovers detected by district and year that
      remains unexplained. We analyzed data from all 57 spillovers during 2007-2013 and
      found that temperature differences explained 36% of the year-to-year variation in
      the total number of spillovers each winter and that distance to surveillance
      hospitals explained 45% of spatial heterogeneity. Interventions to prevent human
      infections may be most important during colder winters. Further work is needed to
      understand how dynamics of bat infections explains spillover risk.

PMID- 29351658
TI  - Intensive versus conventional blood pressure monitoring in a general practice
      population. The Blood Pressure Reduction in Danish General Practice trial: a
      randomized controlled parallel group trial.
AB  - Objective: To compare the effect of a conventional to an intensive blood pressure
      monitoring regimen on blood pressure in hypertensive patients in the general
      practice setting. Design: Randomized controlled parallel group trial with 12
      month follow-up. Setting: One hundred and ten general practices in all regions of
      Denmark. Participants: One thousand forty-eight patients with essential
      hypertension. Intervention: Conventional blood pressure monitoring ('usual
      group') continued usual ad hoc blood pressure monitoring by office blood pressure
      measurements, while intensive blood pressure monitoring ('intensive group')
      supplemented this with frequent home blood pressure monitoring and 24-hour
      ambulatory blood pressure monitoring. Primary outcome measures: Mean day- and
      night-time systolic and diastolic 24-hour ambulatory blood pressure. Secondary
      outcome measures: Change in systolic and diastolic office blood pressure and
      change in cardiovascular risk profile. Results: Of the patients, 515 (49%) were
      allocated to the usual group, and 533 (51%) to the intensive group. The
      reductions in day- and night-time 24-hour ambulatory blood pressure were similar
      (usual group: 4.6 +/- 13.5/2.8 +/- 82 mmHg; intensive group: 5.6 +/- 13.0/3.5 +/-
      8.2 mmHg; P = 0.27/P = 0.20). Cardiovascular risk scores were reduced in both
      groups at follow-up, but more so in the intensive than in the usual group (P =
      0.02). Conclusion: An intensive blood pressure monitoring strategy led to a
      similar blood pressure reduction to conventional monitoring. However, the
      intensive strategy appeared to improve patients' cardiovascular risk profile
      through other effects than a reduction of blood pressure. Trial registration:
      Clinical Trials NCT00244660.

PMID- 29351659
TI  - Smoking status and survival among a national cohort of lung and colorectal cancer
      patients.
AB  - Introduction: The purpose of this study was to explore the association of smoking
      status and clinically relevant duration of smoking cessation with long-term
      survival after lung cancer (LC) or colorectal cancer (CRC) diagnosis. We compared
      survival of patients with LC and CRC who were never-smokers, long-term, medium
      term, and short-term quitters, and current smokers around diagnosis. Methods: We
      studied 5,575 patients in Cancer Care Outcomes Research and Surveillance
      (CanCORS), a national, prospective observational cohort study, who provided
      smoking status information approximately 5 months after LC or CRC diagnosis.
      Smoking status was categorized as: never-smoker, quit > 5 years prior to
      diagnosis, quit between 1-5 years prior to diagnosis, quit less than 1 year
      before diagnosis, and current smoker. We examined the relationship between
      smoking status around diagnosis with mortality using Cox regression models.
      Results: Among participants with LC, never-smokers had lower mortality risk
      compared with current smokers (HR 0.71 95% CI 0.57 to 0.89). Among participants
      with CRC, never smokers had a lower mortality risk as compared to current smokers
      (HR 0.79, 95% CI 0.64 to 0.99). Conclusions: Among both LC and CRC patients,
      current smokers at diagnosis have higher mortality than never-smokers. This
      effect should be further studied in the context of tumor biology. However,
      smoking cessation around the time of diagnosis did not affect survival in this
      sample. Implications: The results from our analysis of patients in the Cancer
      Care Outcomes Research and Surveillance (CanCORS) consortium, a large,
      geographically diverse cohort, show that both lung and colorectal cancer patients
      who were actively smoking at diagnosis have worse survival as compared to never
      smokers. While current smoking is detrimental to survival, cessation upon
      diagnosis may not mitigate this risk.

PMID- 29351660
TI  - Behavior change is not one size fits all: psychosocial phenotypes of childhood
      obesity prevention intervention participants.
AB  - Variability in individuals' responses to interventions may contribute to small
      average treatment effects of childhood obesity prevention interventions. But,
      neither the causes of this individual variability nor the mechanism by which it
      influences behavior are clear. We used qualitative methods to characterize
      variability in students' responses to participating in a childhood obesity
      prevention intervention and psychosocial characteristics related to the behavior
      change process. We interviewed 18 students participating in a school-based
      curriculum and policy behavior change intervention. Descriptive coding, summary,
      and case-ordered descriptive meta-matrices were used to group participants by
      their psychosocial responses to the intervention and associated behavior changes.
      Four psychosocial phenotypes of responses emerged: (a) Activated-successful
      behavior-changers with strong internal supports; (b) Inspired-motivated, but not
      fully successful behavior-changers with some internal supports, whose taste
      preferences and food environment overwhelmed their motivation; (c) Reinforced
      already practiced target behaviors, were motivated, and had strong family
      support; and (d) Indifferent-uninterested in behavior change and only did target
      behaviors if family insisted. Our findings contribute to the field of behavioral
      medicine by suggesting the presence of specific subgroups of participants who
      respond differently to behavior change interventions and salient psychosocial
      characteristics that differentiate among these phenotypes. Future research should
      examine the utility of prospectively identifying psychosocial phenotypes for
      improving the tailoring of nutrition behavior change interventions.

PMID- 29351661
TI  - Estimation of Measurement Uncertainty in Quantitation of Benzoylecgonine (BZE)
      and 11-nor-Delta9-THC-9-carboxylic acid (THCA).
AB  - Calculating measurement uncertainty is a helpful exercise for identifying
      components or steps in a forensic analytical procedure that contribute to
      measurement variance. In this study, we used a bottom up approach to identify
      components in our procedures that contribute to measurement variance in our
      Department of Defense (DoD) Drug Demand Reduction Program (DDRP) Gas
      Chromatography Mass Spectroscopy (GCMS) analytical procedures for benzoylecgonine
      (BZE) and the THC metabolite, 11-nor-Delta9-THC-9-carboxylic acid (THCA) at 125%
      the DDRP concentration threshold (cutoff). Each assay was run 10 times over 30
      days, each assay containing five calibrators and five samples (125%). Measurement
      uncertainty was estimated to be +/-7.6 and +/-0.6 ng/mL, for the BZE and THCA
      methods, respectively (alpha = 0.05). In both assays, method precision and the
      preparation of calibrator and samples were major contributors to measurement
      uncertainty. While this exercise will help with evaluating assay performance from
      a Quality Assurance perspective, these estimates should not be applied in
      interpreting DDRP test results. DDRP cut offs are already inherently conservative
      being above the Limit of Quantitation and were developed taking into
      consideration variability in assay performance across instruments and
      laboratories within the DDRP drug testing system.

PMID- 29351662
TI  - The Versatile Tanycyte: A Hypothalamic Integrator of Reproduction and Energy
      Metabolism.
AB  - The fertility and survival of an individual rely on the ability of the periphery
      to promptly, effectively, and reproducibly communicate with brain neural networks
      that control reproduction, food intake, and energy homeostasis. Tanycytes, a
      specialized glial cell type lining the wall of the third ventricle in the median
      eminence of the hypothalamus, appear to act as the linchpin of these processes by
      dynamically controlling the secretion of neuropeptides into the portal
      vasculature by hypothalamic neurons and regulating blood-brain and blood
      cerebrospinal fluid exchanges, both processes that depend on the ability of these
      cells to adapt their morphology to the physiological state of the individual. In
      addition to their barrier properties, tanycytes possess the ability to sense
      blood glucose levels, and play a fundamental and active role in shuttling
      circulating metabolic signals to hypothalamic neurons that control food intake.
      Moreover, accumulating data suggest that, in keeping with their putative descent
      from radial glial cells, tanycytes are endowed with neural stem cell properties
      and may respond to dietary or reproductive cues by modulating hypothalamic
      neurogenesis. Tanycytes could thus constitute the missing link in the loop
      connecting behavior, hormonal changes, signal transduction, central neuronal
      activation and, finally, behavior again. In this article, we will examine these
      recent advances in the understanding of tanycytic plasticity and function in the
      hypothalamus and the underlying molecular mechanisms. We will also discuss the
      putative involvement and therapeutic potential of hypothalamic tanycytes in
      metabolic and fertility disorders.

PMID- 29351663
TI  - Mini-review: Can non-human leucocyte antigen genes determine susceptibility to
      severe dengue syndromes?
AB  - Dengue viral infections are endemic or epidemic in virtually all tropical
      countries. Among individuals infected with the dengue virus, severe dengue
      syndromes (i.e., dengue haemorrhagic fever and dengue shock syndromes) tend to
      affect only some and this may be due to a combination of host genetic
      susceptibility and viral factors. In this review article we analyse and discuss
      the present knowledge of non-human leucocyte antigen host genetic susceptibility
      to severe dengue syndromes. The relevance of genetic polymorphisms in the
      pathways of antigen recognition, uptake, processing and presentation, activation
      of interferon alpha responses, mast cell and complement activation and T cell
      activation and dengue disease severity has been reviewed and analysed.

PMID- 29351664
TI  - Lipoma arborescens-a rare cause of bilateral ankle tenosynovitis.

PMID- 29351665
TI  - Swiss consumers' willingness to pay and attitudes regarding dual-purpose poultry
      and eggs.
AB  - Chick culling is an efficient and cost-effective method in modern poultry
      farming, but it raises ethical concerns. Dual-purpose poultry (DP), in which
      males are fattened and females are used for egg production, is currently the most
      realistic alternative to culling, as in ovo sexing is not yet viable for
      practical application. Consumers' acceptance of DP products and their willingness
      to pay (WTP) for them have not been studied yet, and we expect that both aspects
      are closely related to the acceptance of and WTP for products from systems
      claiming beyond-conventional animal welfare, such as organic products. Results
      from a survey conducted among 402 consumers at 8 Swiss supermarkets revealed that
      the practice of chick culling was largely unknown (75% of respondents).
      Generally, respondents' knowledge about poultry production was low. The DP
      alternative was preferred to chick culling, but no preference emerged between DP
      and in ovo sexing. Furthermore, the WTP for DP products was proportionally lower
      for chicken than for eggs, probably because of the different price elasticity
      between these products. A regression analysis was used to determine the factors
      influencing consumers' WTP for DP products. Consumers' WTP was positively related
      to knowledge about poultry production, habits tied to purchasing organic or free
      range poultry products, and familiarity with DP products. Therefore, a
      combination of the DP alternative with an organic label is recommended.

PMID- 29351666
TI  - Intraoperative Identification and Preservation of Verbal Memory in Diffuse
      Gliomas: A Matched-Pair Cohort Study.
AB  - BACKGROUND: Recent glioma surgery series with intraoperative electrical
      stimulation (IES) language mapping have demonstrated high rates of postoperative
      memory impairment, raising a question regarding the efficacy of this approach to
      preserve memory. OBJECTIVE: To evaluate if intraoperative identification and
      preservation of verbal memory sites with IES mapping in diffuse gliomas in
      eloquent areas consistently protect patients from long-term postoperative decline
      in short-term memory. METHODS: A cohort of 16 subjects with diffuse low-grade or
      anaplastic gliomas that were operated with IES and intraoperative evaluation of
      language and verbal memory (cohort A) was matched by tumor side, pathology, and
      radiotherapy with a cohort of 16 subjects that were operated with IES and
      evaluation of language (cohort B). Detailed neuropsychological assessment was
      performed before and 6 mo after surgery. RESULTS: Intraoperative memory mapping
      was a strong predictor of verbal memory prognosis. In cohort A, 4 patients
      (26.7%) had a decline of at least one of the 4 short-term memory tests evaluated.
      In cohort B, 11 patients (73.3%) had a decline of at least one of the 4 tests.
      This difference was statistically significant in multivariate analysis (P = .022;
      odds ratio = 9.88; 95% confidence interval = 1.39-70.42). CONCLUSION: Verbal
      memory areas identified intraoperatively with the current paradigm are critically
      involved in verbal memory, as memory impairment can be significantly reduced by
      adapting the resection to avoid those memory areas. Incorporation of verbal
      memory evaluation in stimulation mapping protocols might assist in reducing
      postoperative sequelae and preserving the patient's quality of life.

PMID- 29351667
TI  - What to expect and when: benznidazole toxicity in chronic Chagas' disease
      treatment.
AB  - Background: Benznidazole is one of the two most effective antiparasitic drugs for
      Chagas' disease treatment. However, knowledge about its toxicity profile is
      mostly based on post-marketing observational studies. Objectives: Our study
      combines data from two prospective clinical trials designed to assess the safety
      of the drug newly produced by ELEA Laboratories (Abarax(r)). Methods: Eligible
      participants were selected using a consecutive sampling strategy in the CINEBENZ
      and BIOMARCHA studies between 2013 and 2016 (EUDRACT 2011-002900-34 and 2012
      002645-38, respectively, and clinicaltrials.gov NCT01755403 and NCT01755377,
      respectively). Enrolled subjects received treatment with 5 mg/kg/day benznidazole
      orally in two divided doses for 8 weeks and were followed up fortnightly.
      Results: We observed 305 adverse reactions in 85 of 99 participants (85.9%). Each
      patient had a median of three adverse reactions, 89.5% were mild and the median
      duration was 12 days. Most adverse reactions appeared in the first month of
      treatment except arthritis and peripheral neuropathy. Twenty-six patients did not
      complete treatment: 2 were withdrawn, 1 for ectopic pregnancy and 1 for epilepsy
      relapse due to cysticercosis; 2 were lost to follow-up; and 22 were owing to
      adverse reactions, two of them severe. We observed some unexpected adverse
      reactions that have not been described previously, such as psychiatric symptoms,
      erectile dysfunction, menstrual cycle alterations and lung infiltration.
      Conclusions: There is a very high frequency of adverse reactions to benznidazole.
      Most adverse reactions are mild, but the treatment burden is significant and
      unexpected reactions are not rare. Severe reactions are uncommon, but they can be
      life-threatening. Further studies are necessary to optimize treatment.

PMID- 29351668
TI  - Evaluation of the rapid carbapenem inactivation method (rCIM): a phenotypic
      screening test for carbapenemase-producing Enterobacteriaceae.
AB  - Objectives: Fast and accurate diagnostic tests to identify carbapenemase
      producing Enterobacteriaceae (CPE) are mandatory for proper antimicrobial therapy
      and implementing infection control measures. Here, we have developed a rapid
      Carbapenem Inactivation Method (rCIM) for CPE detection. Methods: The rCIM
      consists of the incubation of a potential carbapenemase producer with meropenem
      discs and use of the resulting supernatant to challenge a susceptible indicator
      strain. Growth of the indicator strain is monitored using a nephelometer. The
      performances of the rCIM were compared with the CIM and Carba NP tests using a
      collection of 113 well-characterized carbapenem-resistant enterobacterial
      isolates, including 85 carbapenemase producers and 28 non-carbapenemase
      producers. In addition, rCIM was compared with the Carba NP test and PCR
      sequencing in a prospective analysis of 101 carbapenem-resistant enterobacterial
      isolates addressed to the French National Reference Center for Antimicrobial
      Resistance in July 2017. Results and discussion: The rCIM correctly identified
      84/85 carbapenemase producers and 28/28 non-carbapenemase producers, yielding a
      sensitivity of 99% and a specificity of 100%, slightly higher than the CIM and
      Carba NP test. In the prospective validation study, the rCIM showed a sensitivity
      and specificity of 97% and 95%, respectively. Two cephalosporinase-hyperproducing
      Enterobacter cloacae gave false-positive results, whereas an IMI-17-producing
      Enterobacter asburiae gave a false-negative result. The result was, however,
      positive when the isolate was grown on selective antibiotic-containing media.
      Conclusions: The rCIM is a rapid (less than 3 h), cheap and accurate test for the
      detection of CPEs, which can be implemented in low-resource settings, making it a
      useful tool for microbiology laboratories.

PMID- 29351669
TI  - How Pairwise Coevolutionary Models Capture the Collective Residue Variability in
      Proteins?
AB  - Global coevolutionary models of homologous protein families, as constructed by
      direct coupling analysis (DCA), have recently gained popularity in particular due
      to their capacity to accurately predict residue-residue contacts from sequence
      information alone, and thereby to facilitate tertiary and quaternary protein
      structure prediction. More recently, they have also been used to predict fitness
      effects of amino-acid substitutions in proteins, and to predict evolutionary
      conserved protein-protein interactions. These models are based on two currently
      unjustified hypotheses: 1) correlations in the amino-acid usage of different
      positions are resulting collectively from networks of direct couplings; and 2)
      pairwise couplings are sufficient to capture the amino-acid variability. Here, we
      propose a highly precise inference scheme based on Boltzmann-machine learning,
      which allows us to systematically address these hypotheses. We show how
      correlations are built up in a highly collective way by a large number of
      coupling paths, which are based on the proteins three-dimensional structure. We
      further find that pairwise coevolutionary models capture the collective residue
      variability across homologous proteins even for quantities which are not imposed
      by the inference procedure, like three-residue correlations, the clustered
      structure of protein families in sequence space or the sequence distances between
      homologs. These findings strongly suggest that pairwise coevolutionary models are
      actually sufficient to accurately capture the residue variability in homologous
      protein families.

PMID- 29351670
TI  - Comparison of two methods for determination of intestinal villus to crypt ratios
      and documentation of early age-associated ratio changes in broiler chickens,.
AB  - The determination of intestinal villus to crypt ratios (VCR) is a common method
      utilized to evaluate effects of various diet regimens on gut microanatomy and for
      the histologic quantification of intestinal responses to disease processes. Two
      methods for the determination of small intestinal VCR were compared in early age
      chickens. A standard method for VCR determination based on 10 villus and crypt
      length measurements in the jejunal region of the small intestine was employed for
      the calculation of villus to crypt length ratio (VCLR). That method was compared
      to a new approach based on a single histomorphometric determination of the crypt
      and total mucosal areas using image analysis software. Subtraction of the crypt
      area from the total area provided the villus area and allowed for the subsequent
      calculation of villus to crypt area ratio (VCAR). At 4 and 18 h posthatch, VCLR
      was higher than that of VCAR, but there was no significant difference between
      VCLR and VCAR at 0 h (hatch) and at 168 h (d 7) posthatch. Nevertheless, the
      pattern of age-associated changes for VCLR and VCAR were comparable throughout
      the early posthatch period. Furthermore, the new method used in determining VCAR
      is subject to less human error, allows for an appreciable reduction in the number
      of measurements required, and facilitates a larger intestinal segment evaluation.
      Standard linear measurements require the selection of variable numbers of villi
      and crypts, whereas the area method only requires selection of a single region
      that incorporates numerous villi and crypts of variable sizes in providing a less
      subjective approach. This is particularly advantageous in studies on intestinal
      disease conditions resulting in marked multifocal variation in villus stature.
      This study further documented age-associated changes occurring in the VCR of the
      small intestine during the early posthatch period. Across the 2 methods used for
      VCR determination, a major and highly significant reduction in the VCR was
      observed to occur between 18 h and 168 h posthatch.

PMID- 29351672
TI  - High treatment success rate among multidrug-resistant tuberculosis patients in
      Myanmar, 2012-2014: a retrospective cohort study.
AB  - Background: Since 2011, Myanmar has adopted domiciliary care for multidrug
      resistant tuberculosis (MDR-TB) patients and implemented several patient-support
      measures such as community-based directly observed treatment, nutritional support
      and financial incentives for patients and providers. We assessed treatment
      outcomes among MDR-TB patients registered for treatment in the Yangon and
      Mandalay Regions of Myanmar during 2012-2014 and factors associated with
      unfavourable treatment outcomes. Methods: We performed a retrospective cohort
      study involving secondary analysis of routine programmatic data extracted from
      the electronic MDR-TB treatment registries. We calculated the adjusted risk ratio
      (aRR) and 95% confidence interval (CI). Results: Of 2185 MDR-TB patients (75% HIV
      tested, 14% HIV positive with 70% of them receiving antiretroviral therapy), 1746
      (80%) were successfully treated (cured and treatment completed) and 20% had
      unfavourable outcomes (14% died, 3% lost to follow-up, 2% failure and 1% not
      evaluated). Compared with young patients (<25 y), patients 25-54 y of age (aRR
      2.0 [95% CI 1.3 to 2.9]) and >55 y (aRR 3.2 [95% CI 2.1 to 4.8]) were more likely
      to have unfavourable outcomes. HIV-positive patients (especially not receiving
      ART; aRR 2.2 [95% CI 1.4 to 3.6]) and patients with 'unknown HIV status' (aRR 1.9
      [95% CI 1.5-2.4]) had a higher risk of unfavourable outcomes compared with HIV
      negative patients. Conclusions: Treatment success was high and deaths accounted
      for three-fourths of unfavourable outcomes. Joint care and management of MDR-TB
      and HIV co-infected patients should be strengthened.

PMID- 29351671
TI  - A novel non-invasive method for evaluating electroencephalograms on laying hens.
AB  - The use of electroencephalograms (EEG) to study the avian brain relative to
      behavior was conducted as early as the 1960's. EEG readings, combined with visual
      cues, provide the ability to elucidate and correlate behaviors to neurological
      and physiological changes in a chicken. The use of EEG recordings in animal
      models require access to the brain to implant electrodes. Having the ability to
      observe EEG activity on sensible birds without surgical implantation could
      broaden the research in this area and give further insight related to the hen's
      state of awareness. The development, construction, and implementation of a
      minimally invasive EEG electrode placement method is described. After
      implementation, test animals were exposed to extreme environmental stressors as
      part of a concurrent depopulation methods study and EEG placement withstood the
      condition changes and corresponding animal physical activity. Sixteen white
      commercial laying hens had three monopolar 32-gauge needle electrodes inserted
      subcutaneously and secured to their head and body. Electrodes were attached to a
      pre-amplifier which transferred EEG signals to a laptop based recording system.
      Once the electrodes were in place, the hens were placed in individual
      treatment/observation chamber then various environmental stressors were applied.
      Verification that the observed brainwave activity was neural and not muscular was
      done using a photic stimulation validation test. Behavior observations were
      recorded to correlate sensible and insensible brainwave activity. The validation
      test and behavior observations demonstrated the method was successful in
      measuring EEG in sensible laying hens. The use of a non-surgical method for
      recording EEG will broaden research capabilities and enhance the understanding of
      a hen's response its environment, eliminate the need for invasive surgical
      procedures, and minimizes the confounding components of anesthesia, brain
      surgery, and recovery. With further refinements, the method could open new
      avenues in avian behavioral and physiological research.

PMID- 29351674
TI  - Erratum.

PMID- 29351675
TI  - Quality in Spine Surgery.
AB  - Health care is expensive in the United States. There is an increasing focus on
      value rather than volume. Accurately measuring quality is a critically important
      step in determining value of care delivered. This article discusses the trials
      and techniques of measuring quality in spine surgery. A detailed analysis of
      advantages and disadvantages of various measures of quality, including process
      measurements, patient-reported outcome measurements, and safety measurements is
      included-from a historical perspective through modern practice.

PMID- 29351676
TI  - Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines
      on the Treatment of Adults with Vestibular Schwannomas: Introduction and Methods.

PMID- 29351677
TI  - Use of Risk Model for Assessment of Residents' Perception of Complexity of
      Surgical Steps: Example of Modular Component Steps of Lumbar Spinal Fusion
      Surgery.
AB  - BACKGROUND: Quality improvement projects increasingly emphasize standardization
      of surgical work flow to optimize operative room efficiency. Removing special
      cause variability resulting from nonsurgical waste is an obvious target; however,
      resident surgical education must be maintained, even in the setting of process
      improvement. OBJECTIVE: To describe the impact of resident-identified "risky" or
      "uncomfortable" procedural steps on operative time during transforaminal lumbar
      interbody fusion (TLIF). METHODS: TLIF procedure steps were defined. An 8 2-part
      questions survey regarding comfort level and perceived risk assessment at each
      step was developed and completed by junior (17) and senior residents (10), and by
      faculty (6) from orthopedic, and neurological surgery. A risk matrix was
      constructed defining 2 zones: a "danger zone"; responses were high risk (3-5) and
      low comfort (1-3), and a "safe zone"; responses were low risk (1-2) and high
      comfort (4-5). One-tailed Chi-square with Yates correction was performed.
      RESULTS: Risk matrix analysis showed a statistical difference among "danger zone"
      respondents between junior resident and faculty groups for exposure, pedicle
      screw placement, neural decompression, interbody placement, posterolateral
      fusion, and hemostasis. A radar graph identifies percent of respondents who fall
      within the "danger zone". CONCLUSION: Resident perception of surgical complexity
      can be evaluated for procedural steps using a risk matrix survey. For TLIF,
      residents may assign more risk and may be less comfortable performing steps in a
      training-level-dependent manner. Identification of particular high-risk or
      uncomfortable steps should prompt strict faculty oversight to improve patient
      safety, monitor resident education, and reduce operative time.

PMID- 29351673
TI  - The Barrow Neurological Institute Grading Scale as a Predictor for Delayed
      Cerebral Ischemia and Outcome After Aneurysmal Subarachnoid Hemorrhage: Data From
      a Nationwide Patient Registry (Swiss SOS).
AB  - BACKGROUND: The Barrow Neurological Institute (BNI) scale is a novel quantitative
      scale measuring maximal subarachnoid hemorrhage (SAH) thickness to predict
      delayed cerebral ischemia (DCI). This scale could replace the Fisher score, which
      was traditionally used for DCI prediction. OBJECTIVE: To validate the BNI scale.
      METHODS: All patient data were obtained from the prospective aneurysmal SAH
      multicenter registry. In 1321 patients, demographic data, BNI scale, DCI, and
      modified Rankin Scale (mRS) score up to the 1-yr follow-up (1FU) were available
      for descriptive and univariate statistics. Outcome was dichotomized in favorable
      (mRS 0-2) and unfavorable (mRS 3-6). Odds ratios (OR) for DCI of Fisher 3
      patients (n = 1115, 84%) compared to a control cohort of Fisher grade 1, 2, and 4
      patients (n = 206, 16%) were calculated for each BNI grade separately. RESULTS:
      Overall, 409 patients (31%) developed DCI with a high DCI rate in the Fisher 3
      cohort (34%). With regard to the BNI scale, DCI rates went up progressively from
      26% (BNI 2) to 38% (BNI 5) and corresponding OR for DCI increased from 1.9 (1.0
      3.5, 95% confidence interval) to 3.4 (2.1-5.3), respectively. BNI grade 5
      patients had high rates of unfavorable outcome with 75% at discharge and 58% at
      1FU. Likelihood for unfavorable outcome was high in BNI grade 5 patients with OR
      5.9 (3.9-8.9) at discharge and OR 6.6 (4.1-10.5) at 1FU. CONCLUSION: This
      multicenter external validation analysis confirms that patients with a higher BNI
      grade show a significantly higher risk for DCI; high BNI grade was a predictor
      for unfavorable outcome at discharge and 1FU.

PMID- 29351678
TI  - Endoscopic Transcranial Duraplasty for Rhinoliquorrhea: A Cadaveric Study.
AB  - BACKGROUND: Repair of the anterior skull base for cerebrospinal fluid leak
      requires either endoscopic endonasal approach or open transcranial approach.
      OBJECTIVE: To present a less invasive surgical procedure for sealing of the
      entire anterior fossa floor for traumatic rhinoliquorrhea. METHODS: Cadaver study
      in 3 head specimens. Endoscopic placement of a furled bovine pericardial patch
      bilaterally along the sphenoid ridge and planum in guidewire technique. Unfurling
      and spreading of the patch under endoscope assistance. RESULTS: Patch placement
      was feasible in all 3 specimens without visible injuries to the frontal lobes.
      Dissection and preservation of the olfactory tracts was only possible for 50% of
      olfactory tracts. CONCLUSION: Endoscopic transcranial keyhole duraplasty is a
      promising concept for traumatic rhinoliquorrhea.

PMID- 29351679
TI  - Landmarks for Identifying the Suprascapular Foramen Anteriorly: Application to
      Anterior Neurotization and Decompressive Procedures.
AB  - BACKGROUND: Additional landmarks for identifying the suprascapular nerve at its
      entrance into the suprascapular foramen from an anterior approach would be useful
      to the surgeon. OBJECTIVE: To identify landmarks for the identification of this
      hidden site within an anterior approach. METHODS: In 8 adult cadavers (16 sides),
      lines were used to connect the superior angle of the scapula, the acromion, and
      the coracoid process tip thus creating an anatomic triangle. The suprascapular
      nerve's entrance into the suprascapular foramen was documented regarding its
      position within this anatomical triangle. Depths from the skin surface and
      specifically from the medial-most point of the clavicular attachment of the
      trapezius to the suprascapular nerve's entrance into the suprascapular foramen
      were measured using calipers and a ruler. The clavicle was then fractured and
      retracted superiorly to verify the position of the nerve's entrance into the
      suprascapular foramen. RESULTS: From the trapezius, the nerve's entrance into the
      foramen was 3 to 4.2 cm deep (mean, 3.5 cm). The mean distance from the tip of
      the corocoid process to the suprascapular foramen was 3.8 cm. The angle best used
      to approach the suprascapular foramen from the surface was 15 degrees  to 20
      degrees . CONCLUSION: Based on our study, an anterior suprascapular approach to
      the suprascapular nerve as it enters the suprascapular foramen can identify the
      most medial fibers of the trapezius attachment onto the clavicle and insert a
      finger at an angle of 15 degrees  to 20 degrees  laterally and advanced to an
      average depth of 3.5 cm.

PMID- 29351680
TI  - Tentative Stacking Technique with Tandem Clipping and Bypass for an MCA Aneurysm:
      3-Dimensional Operative Video.

PMID- 29351681
TI  - Keyhole Contralateral Interhemispheric Endoscopic-Assisted Resection of an
      Ependymoma of the Third Ventricle.

PMID- 29351682
TI  - Radial Artery Fascial Flow-Through Free Flap for Combined Revascularization in
      Moyamoya Disease.
AB  - BACKGROUND: Free flaps are commonly used by other surgical subspecialties for
      soft tissue reconstruction and revascularization. Cranial applications of these
      flaps have been limited to only a single case report. OBJECTIVE: To present a new
      technique for combined revascularization in moyamoya disease using a flow-through
      free flap. METHODS: Data were obtained from an Institutional Review Board
      approved, prospectively maintained database with informed consent from the
      patient. RESULTS: A 28-yr-old patient presented with progressive stenosis of the
      proximal anterior cerebral artery resulting in ischemic infarcts. Direct
      revascularization of the anterior cerebral artery territory and indirect
      revascularization of the middle cerebral artery with a large vascularized fascial
      pedicle was performed. CONCLUSION: Flow-through free flaps offer a unique
      combination of revascularization and a large vascularized pedicle. This technique
      highlights the application of these flaps for revascularization in moyamoya
      disease and the value of multidisciplinary collaboration. Revascularization will
      likely play an increasing role in the open surgical treatment of cerebrovascular
      disease. We believe that flow-through free flaps will be a contribution to the
      future of revascularization in neurosurgery.

PMID- 29351683
TI  - Novel Bilateral Extracavitary Approach for Thoracolumbar Decompression.
AB  - BACKGROUND: Bilateral extracavitary approach (BECA) is an option for
      decompression cases that require a more extended ventral approach. The clear
      advantage is increased accessibility to the most ventral aspects of the spine
      from a bilateral perspective. OBJECTIVE: To assess the safety and efficacy of
      thoracic and thoracolumbar decompression and/or reconstruction from BECA.
      METHODS: A retrospective chart review was performed reviewing all patients who
      underwent BECA for thoracolumbar decompression from 2003 to 2012 at our
      institution. We recorded patient baseline characteristics, physical exam,
      surgical indications, perioperative interventions, and outcomes. RESULTS: We
      performed 82 lateral extracavitary approaches and 10 BECAs. BECA indications
      included neoplasm, infection, and kyphotic deformity. Average patient age was 58
      yr; 80% of BECA patients were male. Estimated blood loss was typically 1 to 3 L.
      Average length of stay postoperative was 12 d. Two patients required revisions;
      one for infection and one for revision of misplaced hardware. Eight patients
      improved at least one grade on the American Spinal Injury Association Impairment
      Scale (ASIA) or was originally ASIA E. Two patients declined 1 to 2 ASIA grades.
      Average length of follow-up was 16.8 mo. CONCLUSION: BECA is an efficient
      technique with acceptable complication rates and similar risks to unilateral
      approaches. It should be considered when extensive bilateral decompression and/or
      reconstruction of the anterior thoracic or thoracolumbar spine is required.

PMID- 29351684
TI  - Endoscopic Occipital Transtentorial Approach for Pineal Region Tumor.

PMID- 29351685
TI  - Extended Retrosigmoid Craniotomy and Clip Occlusion of a Petrosal Tentorial Dural
      Arteriovenous Fistula (Type 5): Operative Video.

PMID- 29351686
TI  - Basilar Artery Ectasia Causing Trigeminal Neuralgia: An Evolved Technique of
      Transpositional Suture-Pexy.
AB  - BACKGROUND: Microvascular decompression for patients with trigeminal neuralgia
      (TGN) is widely accepted as one of the modalities of treatment. The standard
      approach has been retrosigmoid suboccipital craniotomy with placement of a Teflon
      pledget to cushion the trigeminal nerve from the offending artery, or cauterize
      and divide the offending vein(s). However, in cases of severe compression caused
      by a large artery, the standard decompression technique may not be effective.
      OBJECTIVE: To describe a unique technique of vasculopexy of the ectatic basilar
      artery to the tentorium in a patient with TGN attributed to a severely ectatic
      and tortuous basilar artery. A case series of patients who underwent this
      technique of vasculopexy for arterial compression is presented. METHODS: The
      patient underwent a subtemporal transtentorial approach and the basilar artery
      was mobilized away from the trigeminal nerve. A suture was then passed through
      the wall of the basilar artery (tunica media) and secured to the tentorial edge,
      to keep the artery away from the nerve. RESULTS: The neuralgia was promptly
      relieved after the operation, with no complications. A postoperative magnetic
      resonance imaging scan showed the basilar artery to be away from the trigeminal
      root. In a series of 7 patients who underwent this technique of vasculopexy, no
      arterial complications were noted at short- or long-term follow-up. CONCLUSION:
      Repositioning and vasculopexy of an ectatic basilar artery for the treatment of
      TGN is safe and effective. This technique can also be used for other neuropathies
      that result from direct arterial compression.

PMID- 29351687
TI  - Intraoperative Transpedicular Onyx Injection to Reduce Vascularity of a Thoracic
      Hemangiopericytoma After Unsuccessful Preoperative Endovascular Embolization: a
      Technical Report.
AB  - BACKGROUND AND IMPORTANCE: Hemangiopericytoma is a rare vascular tumor with
      central nervous system involvement representing only 1% of central nervous system
      tumors. They rarely affect the vertebral column. Complete surgical resection is
      the treatment of choice for hemangiopericytoma given their high rates of local
      recurrence. However, the high vascularity of such tumors with the risk of massive
      bleeding during surgery represents a significant challenge to surgeons.
      Therefore, preoperative endovascular embolization via the transarterial route has
      been advocated. CLINICAL PRESENTATION: In the current study, we present a case of
      a T12 hemangiopericytoma that was managed by a 2-stage surgical resection, with
      the use of intraoperative transpedicular onyx injection to reduce intraoperative
      blood loss following an unsuccessful trial of preoperative endovascular
      embolization. CONCLUSION: Preoperative endovascular embolization is not feasible
      in some cases due to the location of the segmental or radiculomedullary arteries
      in relation to tumor feeders and, rarely, small size of these arterial feeders.
      Percutaneous injection of onyx is an option. In this case report, we discuss
      direct intraoperative injection via a transpedicular route as a safe and
      effective method for decreasing the vascularity of some lesions and improving
      intraoperative blood loss.

PMID- 29351688
TI  - Three-Hand Endoscopic Endonasal Transsphenoidal Surgery: Experience With an
      Anatomy-Preserving Mononostril Approach Technique.
AB  - BACKGROUND: Variations on the endoscopic transsphenoidal approach present unique
      surgical techniques that have unique effects on surgical outcomes, extent of
      resection (EOR), and anatomical complications. OBJECTIVE: To analyze the learning
      curve and perioperative outcomes of the 3-hand endoscopic endonasal mononostril
      transsphenoidal technique. METHODS: Prospective case series and retrospective
      data analysis of patients who were treated with the 3-hand transsphenoidal
      technique between January 2007 and May 2015 by a single neurosurgeon. Patient
      characteristics, preoperative presentation, tumor characteristics, operative
      times, learning curve, and postoperative outcomes were analyzed. Volumetric EOR
      was evaluated, and a logistic regression analysis was used to assess predictors
      of EOR. RESULTS: Two hundred seventy-five patients underwent an endoscopic
      transsphenoidal surgery using the 3-hand technique. One hundred eighteen patients
      in the early group had surgery between 2007 and 2010, while 157 patients in the
      late group had surgery between 2011 and 2015. Operative time was significantly
      shorter in the late group (161.6 min) compared to the early group (211.3 min, P =
      .001). Both cohorts had similar EOR (early group 84.6% vs late group 85.5%, P =
      .846) and postoperative outcomes. The learning curve showed that it took 54 cases
      to achieve operative proficiency with the 3-handed technique. Multivariate
      modeling suggested that prior resections and preoperative tumor size are
      important predictors for EOR. CONCLUSION: We describe a 3-hand, mononostril
      endoscopic transsphenoidal technique performed by a single neurosurgeon that has
      minimal anatomic distortion and postoperative complications. During the learning
      curve of this technique, operative time can significantly decrease, while EOR,
      postoperative outcomes, and complications are not jeopardized.

PMID- 29351689
TI  - Microvascular Decompression for Patients With Hemifacial Spasm Associated With
      Common Trunk Anomaly of the Cerebellar Arteries-Case Study and Review of
      Literature.
AB  - BACKGROUND: Few previous studies have described the origin of both anterior and
      posterior inferior cerebellar arteries from one vessel as a common trunk anomaly.
      No previous studies have clearly described the aforementioned anomaly depending
      on intraoperative endoscopic visualization. OBJECTIVE: To evaluate the
      association of a common trunk anomaly with hemifacial spasm, which makes
      microvascular decompression more challenging. METHODS: All patients with common
      trunk anomaly associated with hemifacial spasm who received surgical treatment
      between 2006 and 2015 in our institution were identified in our prospectively
      collected database. Detection of the common trunk anomaly was performed using the
      intraoperative high-definition endoscopic inspection and confirmed by a
      retrospective review of the obtained operative videos. RESULTS: Out of 248 cases
      of hemifacial spasm, 21 cases with a common trunk anomaly were detected, with an
      incidence rate of 8.5%. In 6 cases, the spasm was caused by more than 1 offending
      vessel "complex compression." In 19 cases, total recovery occurred on follow-up,
      while in 1 case, 90% recovery occurred. One patient was spasm-free immediately
      after surgery, but died 3 wk after operation from herpes encephalitis.
      CONCLUSION: Common trunk anomaly in hemifacial spasm is rare. The surgical
      technique is mostly identical to decompression with normally arising vessels.
      However, in case of a bifurcation situated close to the compression site where
      the offending vessel cannot be transposed freely, an extensive cushioning along
      the trunk and the offending vessels with teflon pledgets should be performed. The
      presence of a common trunk anomaly does not affect the surgical results.

PMID- 29351690
TI  - The Transcondylar Approach to Access Symptomatic Arachnoid Cysts of the
      Hypoglossal Canal.
AB  - BACKGROUND AND IMPORTANCE: A direct transcondylar approach to treat symptomatic
      arachnoid cysts of the hypoglossal canal has not yet been described in the
      literature. CLINICAL PRESENTATION: Here, we present a skull base approach in 2
      female patients (68 and 38 yr) with progressive dysphagia, dysarthria, half-sided
      weakness, and atrophy of the tongue due to an arachnoid cyst of the hypoglossal
      canal. After patient informed consent, both patients were successfully operated
      on without complications using a transcondylar approach, and their symptoms
      improved 3 mo after surgery; in both patients, resection of the cyst was
      confirmed using magnetic resonance imaging. Review of the literature revealed 4
      surgically treated cases of hypoglossal cysts operated on through a paramedian
      suboccipital craniotomy from a medial to lateral surgical corridor. CONCLUSION:
      This is the first description of the transcondylar surgical approach to safely
      operate on symptomatic arachnoid cysts located in the hypoglossal canal. The
      isolated transcondylar approach is useful in selective cases when the pathology
      is located within the hypoglossal canal only and the skull base anatomy allows a
      direct approach.

PMID- 29351691
TI  - OUT-OF-FIELD DOSES IN CHILDREN TREATED FOR LARGE ARTERIOVENOUS MALFORMATIONS
      USING HYPOFRACTIONATED GAMMA KNIFE RADIOSURGERY AND INTENSITY-MODULATED RADIATION
      THERAPY.
AB  - The purpose of this study was to measure out-of-field organ doses in two
      anthropomorphic child phantoms for the treatment of large brain arteriovenous
      malformations (AVMs) using hypofractionated gamma knife (GK) radiosurgery and to
      compare these with an alternative treatment using intensity-modulated radiation
      therapy (IMRT). Target volume was identical in size and shape in all cases.
      Radiophotoluminescent (RPL), thermoluminescent (TL) and optically stimulated
      luminescent (OSL) dosimeters were used for out-of-field dosimetry during GK
      treatment and a good agreement within 1-2% between results was shown. In
      addition, the use of multiple dosimetry systems strengthens the reliability of
      the findings. The number of GK isocentres was confirmed to be important for the
      magnitude of out-of-field doses. Measured GK doses for the same distance from the
      target, when expressed per target dose and isocentre, were comparable in both
      phantoms. GK out-of-field doses averaged for both phantoms were evaluated to be
      120 mGy/Gy for eyes then sharply reduced to 20 mGy/Gy for mandible and slowly
      reduced up to 0.8 mGy/Gy for testes. Taking into account the fractionation
      regimen used to treat AVM patients, the total treatment organ doses to the out-of
      field organs were calculated and compared with IMRT. The eyes were better spared
      with GK whilst for more distant organs doses were up to a factor of 2.8 and 4
      times larger for GK compared to IMRT in 5-year and 10-year old phantoms,
      respectively. Presented out-of-field dose values are specific for the
      investigated AVM case, phantoms and treatment plans used for GK and IMRT, but
      provide useful information about out-of-field dose levels and emphasise their
      importance.

PMID- 29351692
TI  - Homonymous Hemianopia in Children and Adolescents: An MRI Study.
AB  - AIM:  Diagnosing homonymous hemianopia (HH) in children can be difficult due to
      inability to comply with perimetry. Therefore, HH can often only be suspected by
      magnetic resonance imaging (MRI) showing lesions to the retrochiasmatic visual
      pathways. The aim of our retrospective observational cross-sectional study was to
      improve the radiologic detection of HH. METHODS:  MRIs of 21 subjects (5-17 years
      old) with ophthalmologically confirmed HH (14 complete, 7 incomplete hemianopias)
      were analyzed. In addition, we asked four questions looking at everyday problems
      possibly related to the HH. The questions asked for (1) problems in avoiding
      objects/people, (2) bumping into objects/people, (3) difficulties in judging
      stairs, and (4) difficulties in grasping objects. RESULTS:  We found
      neuroanatomical correlates of the HH in all 21 participants, with the optic
      radiation being involved in almost all participants (20/21). Everyday problems
      possibly related to the HH were reported for all nine patients with
      postneonatally acquired complete hemianopias. In contrast, no such problems were
      reported for seven patients with incomplete HH (7/7) and for 3/5 patients with
      complete hemianopias due to pre-, peri- or neonatally acquired brain lesions.
      INTERPRETATION:  A dedicated radiologic analysis of the retrochiasmatic optic
      pathway should routinely be performed in children with brain lesions to identify
      children with HH. Early onset and incomplete HH are predictors for successful
      compensation.

PMID- 29351693
TI  - Editor's Commentary.

PMID- 29351694
TI  - Treatment Outcomes for Right-Sided Endocarditis in Intravenous Drug Users: A
      Systematic Review and Analysis of Outcomes in a Tertiary Centre.
AB  - BACKGROUND: The increasing prevalence of intravenous drug users (IVDU) has
      resulted in higher incidence of right-sided infective endocarditis (RSIE).
      However, treatment guidelines for RSIE in IVDU are not well defined. The aim is
      to evaluate efficacy of different treatment strategies in reducing mortality and
      to describe treatment outcomes. METHODS: We systematically reviewed the
      literature using PubMed, Cochrane, CENTRAL, OvidEMBASE, Web of Science, and
      Medline databases to include prospective studies that compare mortality rates
      among IVDU with RSIE receiving isolated medical treatment versus those receiving
      medical-surgical treatment. In conjunction, analysis of 27 RSIE patients
      (including IVDU) treated at authors' institution was done to supplement the
      findings. Kaplan-Meier survival rates following hospital admission and cumulative
      incidence estimates for hospital re-admission were obtained. RESULTS: A total of
      nine studies (all with low or marginal risk of bias) met inclusion criteria. The
      prevalence of RSIE among IVDU with infective endocarditis varied from 34% to
      100%. Seven studies compared medical versus medical-surgical therapy with less
      than 30% needing surgery. Mortality was higher in patients receiving surgical
      therapy. There were 27 RSIE (16 non-IVDU and 11 IVDU) analyzed at the authors'
      institution. Survival at 30 days, 1 year, and 3 years were 89%, 82%, and 78%,
      respectively, and repeat hospitalization for recurrent endocarditis were 8%, 17%,
      and 23%, respectively. CONCLUSIONS: There is paucity around optimal RSIE
      management strategy for IVDU that can decrease mortality. Surgical management of
      RSIE may be associated with increased mortality over medical management mainly
      due to advanced surgical indications.

PMID- 29351695
TI  - Reasons for Failure of Systemic-to-Pulmonary Artery Shunts in Neonates.
AB  - BACKGROUND:  Systemic-to-pulmonary artery shunt placement is an established
      palliative procedure for congenital heart disease. Although it is thought to be a
      simple operation, it is associated with significant morbidity and mortality.
      METHODS:  Data for all neonates who underwent surgery for a systemic-to-pulmonary
      artery shunt between 2000 and 2016 were reviewed. The study endpoints were shunt
      failure and shunt-related mortality. Shunt failure was defined as a shunt
      dysfunction because of thrombosis or stenosis requiring intervention or
      reoperation; shunt mortality was defined as death because of a shunt dysfunction.
      RESULTS:  A total of 305 shunts (central shunt, n = 135; Blalock-Taussig shunt, n
      = 170) were implanted in 280 patients. The median patients' age at the time of
      surgery was 9 days (1-31 days). The median shunt size was 3.5 mm (3-4 mm). Twenty
      four patients (8%) were diagnosed with a shunt failure, with a median time of 7
      days (0-438 days). Freedom from shunt failure at 1 year was 91.6% +/- 2%. A shunt
      related mortality was ascertained for 12 patients (4%). Freedom from shunt
      related mortality at 1 year was 96% +/- 1%. Perioperative platelet transfusion (p
      = 0.01), central shunt (p = 0.02), 3-mm shunt size (p = 0.02), and postoperative
      extra corporeal membrane oxygenation (ECMO) (p < 0.01) were identified as risk
      factors for shunt failure. Platelet transfusion (p = 0.04) and postoperative ECMO
      (p < 0.01) were further identified as risk factors for shunt mortality.
      CONCLUSION:  Based on these data, we recommend implanting a modified Blalock
      Taussig shunt of at least 3.5 mm in neonates. Perioperative platelet transfusion
      and postoperative ECMO increase the risk of shunt failure.

PMID- 29351696
TI  - Risk of Primary Spontaneous Pneumothorax According to Chest Configuration.
AB  - BACKGROUND: We compared the chest configurations of patients with primary
      spontaneous pneumothorax (PSP) and age-sex-matched controls to determine the
      presence of chest wall deformities in patients with PSP. METHODS: We
      retrospectively enrolled 166 male patients with PSP (age, 18-19 years) and 85 age
      sex-matched controls without PSP, who simultaneously underwent chest computed
      tomography (CT) and radiography at one of two institutes. After correcting for
      height, the following thoracic parameters were comparatively evaluated between
      the two groups: maximal internal transverse (T) and anteroposterior (W) diameters
      of the chest, maximal internal lung height (H), Haller index (T/W), and T/Height,
      T/H, W/Height, W/H, and H/Height ratios. RESULTS: Patients were taller than the
      control subjects (176.5 cm +/- 5.9 cm versus 174.4 cm +/- 5.6 cm; p = 0.007).
      After controlling for height, the patient group exhibited lower T and W and
      greater H and Haller index values than the control group (T: 95% confidence
      interval [CI], 24.8-25.2 cm versus 25.9-26.5; W: 95% CI, 8.9-9.2 cm versus 10.1
      10.6 cm; H: 95% CI, 25.2-25.9 cm versus 23.4-24.4 cm; and Haller index, 95% CI,
      2.7-2.9 versus 2.4-2.6; all, p < 0.001). The patient group also exhibited lower
      T/Height, T/H, W/Height, and W/H ratios and greater H/Height ratio than the
      control group. CONCLUSIONS: Patients with PSP have an anteroposteriorly flatter,
      laterally narrower, and craniocaudally taller thorax than subjects without PSP,
      suggesting that chest configuration is associated with the development of
      pneumothorax.

PMID- 29351697
TI  - Roles of Transit-Time Flow Measurement for Coronary Artery Bypass Surgery.
AB  - Transit-time flow measurement (TTFM) has been increasingly applied to detect
      graft failure during coronary artery bypass grafting (CABG), because TTFM is less
      invasive, more reproducible, and less time consuming. Many authors have attempted
      to validate TTFM and to gain the clear cutoff values and algorithm in TTFM to
      predict graft failure. The TTFM technology has also been shown to be a useful
      tool to investigate CABG graft flow characteristics and coronary circulation
      physiology. It is important to recognize the practical roles of TTFM in the
      cardiac operating room by review and summarize the literatures.

PMID- 29351698
TI  - Endoscopic mucosal resection of rectal squamous cell papilloma.

PMID- 29351699
TI  - Endoscopic submucosal tunnel dissection for early squamous cell carcinoma of the
      esophagus.

PMID- 29351700
TI  - Successful treatment of an impacted lithotripter basket in the common bile duct
      with intracorporeal electrohydraulic lithotripsy.

PMID- 29351701
TI  - A rare cause of small-bowel bleeding: haemorrhagic small-bowel lymphangioma
      diagnosed by antegrade double-balloon enteroscopy.

PMID- 29351702
TI  - Endoscopic ultrasonography-guided obliteration of a left inferior phrenic artery
      pseudoaneurysm in a patient with alcoholic chronic pancreatitis.

PMID- 29351703
TI  - A wormy surprise: ERCP for intrabiliary drainage of a hydatid cyst.

PMID- 29351704
TI  - Safety of cold snare polypectomy for duodenal adenomas in familial adenomatous
      polyposis: a prospective exploratory study.
AB  - BACKGROUND:  Cold snare polypectomy (CSP) to remove multiple duodenal adenomas
      (MDAs) in patients with familial adenomatous polyposis (FAP) could be an
      effective and less invasive method than more extensive surgery. The aim of the
      present study was to determine the safety of this procedure. METHODS:  This
      prospective exploratory study included 10 consecutive patients with FAP and MDAs
      who underwent CSP for as many as 50 duodenal adenomas. The primary outcome was
      the incidence of severe adverse events. RESULTS:  10 patients were enrolled and
      underwent 332 CSPs from June 2016 to January 2017. The median procedure time was
      33 minutes (range 25 - 53), and the median number of polyps removed during a
      single session was 35 (range 10 - 50). Most of the removed polyps were <= 10 mm.
      None of the 10 patients experienced a severe adverse event. One patient developed
      arterial bleeding during the procedure, but it was easily managed using
      hemoclips. CONCLUSIONS:  CSP for MDAs in patients with FAP was safe. The long
      term efficacy of this procedure should be investigated.

PMID- 29351705
TI  - Percutaneous-endoscopic rendezvous procedure for the management of bile duct
      injuries after cholecystectomy: short- and long-term outcomes.
AB  - BACKGROUND:  Bile duct injury (BDI) remains a daunting complication of
      laparoscopic cholecystectomy. In patients with complex BDI, a percutaneous
      endoscopic rendezvous procedure may be required to establish bile duct
      continuity. The aim of this study was to assess short- and long-term outcomes of
      the rendezvous procedure. METHODS:  All consecutive patients with BDI referred to
      our tertiary referral center between 1995 and 2016 were analyzed. A rendezvous
      procedure was performed when endoscopic or radiologic intervention failed, and
      when deemed feasible by a dedicated multidisciplinary team including
      hepatopancreaticobiliary surgeons, gastrointestinal endoscopists, and
      interventional radiologists. Classification of BDI, technical success of the
      rendezvous procedure, procedure-related adverse events, and outcomes were
      assessed. RESULTS:  Among a total of 812 patients, rendezvous was performed in 47
      (6 %), 31 (66 %) of whom were diagnosed with complete transection of the bile
      duct (Amsterdam type D/Strasberg type E injury). The primary success rate of
      rendezvous was 94 % (44 /47 patients). Overall morbidity was 18 % (10 /55
      procedures). No life-threatening adverse events or 90-day mortality occurred.
      After a median follow-up of 40 months (interquartile range 23 - 54 months),
      rendezvous was the final successful treatment in 26 /47 patients (55 %). In 14
      /47 patients (30 %), rendezvous acted as a bridge to surgery, with
      hepaticojejunostomy being chosen either primarily or secondarily to treat
      refractory or relapsing stenosis. CONCLUSIONS: In experienced hands, rendezvous
      was a safe procedure, with a long-term success rate of 55 %. When endoscopic or
      transhepatic interventions fail to restore bile duct continuity in patients with
      BDI, rendezvous should be considered, either as definitive treatment or as a
      bridge to elective surgery.

PMID- 29351707
TI  - [Crying Retina Sign].

PMID- 29351706
TI  - MicroRNAs and Target Genes in Pituitary Adenomas.
AB  - Pituitary adenomas account for the top three primary intracranial tumors in terms
      of total incidence rates. The clinical symptoms presented by the disease are
      often characterized by a series of systemic endocrine disorders, severe
      occupational lesions, and even some malignant features, and therefore early
      diagnosis and predicting recurrence would be instructive for clinical treatment
      of pituitary adenomas. An increasing number of specific microRNA (miRNA)
      expression signatures have been identified in pituitary, and miRNAs are related
      with the pituitary tumorigenesis, dysfunction, neurodegeneration, and metastatic
      non-functioning pituitary carcinoma. Here, this paper reviews the effects of
      aberrant miRNA expression in human pituitary adenomas and summarizes some
      corresponding target genes and biological significance over the last 7 years
      (2010-2017).

PMID- 29351708
TI  - Eyelid Reconstruction: Pediculated versus Non-Pediculated.
AB  - BACKGROUND: To compare the functional and cosmetic outcome of pediculated versus
      free anterior and posterior lamella reconstruction after large eyelid defects due
      to malignancy excision. PATIENTS AND METHODS: A retrospective study over 2 years
      with 12 patients matching the criterion of pediculated versus non-pediculated
      transplants out of a cohort of 124 tumor excisions. The mean age was 76 +/- 8
      years of the 7 male and 5 female patients. In the majority of cases, more than
      half of the eyelid was excised. The posterior lamella was always reconstructed
      with tarsal tissue, and the anterior lamella mostly with an upper eyelid skin
      graft. The postoperative follow-up time was between 2 months and 1 year. RESULTS:
      Nodular basal cell carcinoma was the prevailing histology (6 patients). The
      reconstruction techniques included a Hughes procedure (four patients) or a free
      tarsal graft with a pediculated skin flap (four patients), respectively. In the
      remaining four patients, a combination of pediculated/free anterior AND posterior
      lamellae was performed. Four patients had a one-stage and eight patients a 2nd
      stage procedure with a mean time until tarsoconjunctival flap reopening of 16 +/-
      2 days. CONCLUSIONS: No difference was found in the final functional outcome in
      pediculted versus free grafts. The cosmetic result was better in anterior lamella
      reconstructions with a pediculated flap, which usually allows a one-stage
      procedure. The 2nd stage procedure could be performed after 2 weeks without any
      complications.

PMID- 29351709
TI  - [Validation of the Screening for Complex PTSD (SkPTBS) - Revision].
AB  - BACKGROUND: The aim was to develop further a screening instrument for complex
      posttraumatic stress disorder (cPTSD). The screening for cPTSD (SkPTBS) tests a)
      potential traumatic experiences, b) influential features and risk factors, and c)
      symptoms of cPTSD. The SkPTBS by Dorr et al. (2016) was revised according to the
      current ICD-11 criteria set proposal for cPTSD and is explored in its revised
      edition. METHOD: Impacts of long-lasting interpersonal trauma were tested in
      inpatients of psychosomatic rehabilitation and in patients consulting a
      university outpatient center for trauma therapy. Patients filled out the
      screening at the beginning of their treatment (N=525, among these n=359
      rehabilitation patients and n=157 in the outpatient center, mean age 48 years,
      68% female). Later diagnosed complex PTSD as well as results of the SCID and the
      Interview for complex PTSD (IkPTBS) served as primary validation criteria.
      RESULTS: 88 patients (17%) were diagnosed with complex PTSD. Metric SkPTBS items
      were selective and the scale had an internal reliability of Cronbachs alpha=0.91.
      The one-dimensional factor structure was replicated. SkPTBS correlated moderately
      with posttraumatic symptoms measured by IES-15, with dissociative symptoms (DES
      Taxon), depressive symptoms (in BDI-II, PHQ-9), and global symptom severity (in
      SCL-90-R). Finally, norms for different groups of age, diagnosis and treatment
      settings were developed. CONCLUSION: The SkPTBS revision is a feasible and brief
      instrument to identify patients at risk for complex PTSD. It is provided freely
      and can be applied for diagnostic and therapeutic purposes.

PMID- 29351710
TI  - [Implementation of an Internet-Based Self-Help for Patients Waiting for
      Outpatient Psychotherapy - First Results].
AB  - INTRODUCTION: Numerous studies prove the efficacy of internet-based self-help
      programs, but integration into the health-care system was rarely investigated.
      The present study addresses the implementation of an internet-based self-help
      program into routine care of patients with depressive symptoms waiting for
      psychotherapy at the university outpatient center. MATERIAL AND METHODS: Patients
      waiting for outpatient psychotherapy were randomly assigned to either a control
      group or an intervention group that received access to the internet-based program
      Deprexis during the waiting period. Depressive symptoms were assessed before and
      after waiting. Additionally, expectations and program use of participants were
      exploratively examined. RESULTS: Only half of the patients who were informed
      about the study were interested in participation. Participants used about half of
      the modules in the program Deprexis. Depressive symptoms were reduced in both
      groups during the waiting time. However, the symptom improvements were not
      significant. DISCUSSION: Integration of internet-based self-help programs into
      the German health-care system should include support by a psychotherapist.
      Preferences of participants should also be considered to enhance adherence and
      efficacy of the program. CONCLUSION: Internet-based self-help programs for use in
      the waiting time for outpatient psychotherapy of patients with depression should
      involve guidance.

PMID- 29351711
TI  - [Beck Anxiety Inventory German Version - A Reliable, Valid, Patientfriendly
      Instrument for Measuring Clinical Anxiety].
AB  - The Beck Anxiety Inventory (BAI) is available in German. Apart from data in its
      manual, there are no further reports on the psychometric properties of this
      questionnaire and on its suitability for clinical use in Germany. This study
      therefore offers an independent investigation into the psychometrics as well as
      the clinical characteristics of the BAI. Three samples with n=145, n=90, and
      n=174 comprised inpatients diagnosed with anxiety disorders and treated in a
      large psychosomatic hospital. In addition to the BAI, the clinician rating
      Hamilton Anxiety Scale (HamA), the State-Trait-Anxiety Inventory (STAI) as well
      as the two anxiety subscales of the Symptom Checklist 90 (SCL 90) were used to
      establish convergent validity. For divergent validity, patients filled out
      questionnaires measuring the motivational construct of Action versus State
      Orientation as well as the motivational scale of the Freiburg Personality
      Inventory (FPI). The Beck Depression Inventory II (BDI II) and a single item
      targeting a patient's psychotherapy goal achievement complemented the measures.
      Data collection times were admission to inpatient treatment, discharge from the
      hospital, and 6-month follow-up. For a subsample of patients, additional data
      from the weeks prior to hospital admission allowed for a test of the nonspecific
      Hope for Success in the absence of therapy. The inpatient intervention consisted
      of approximately 6 weeks of cognitive-behavioral psychotherapy. The German BAI is
      considered to be unidimensional. It is a homogeneous, reliable (3-day test
      retest) inventory with excellent item characteristics. The data suggested good
      convergent validity with other anxiety measures, and divergent validity. However,
      the BAI and the BDI-II exhibited a midrange correlation with each other, which
      was an unexpected result. Groups of patients with different diagnoses could be
      differentiated. The questionnaire shows sensitivity to specific and nonspecific
      change. Goal attainment goes along with BAI results. In conclusion, the BAI is a
      psychometrically sound inventory; it is brief, user-friendly and therefore
      appropriate for use in inpatient and outpatient psychotherapy settings.

PMID- 29351712
TI  - [Immigrated Physicians: Chances and Challenges].
AB  - BACKGROUND AND OBJECTIVE: In the health care infrastructure of Germany a demand
      for physicians with immigrant background exists. The situation of immigrated
      physicians is largely unexplored so far. In the framework of a pilot study
      stressors and resources of physicians with immigrant background have been
      explored concerning their migration-related experiences at German hospitals, and
      within the medical team. METHODS: As part of a qualitative analysis 8 physicians
      with immigrant background have been interviewed (problem-centered interview) from
      July to September 2014. The respondents stemmed from countries of the European
      Union and of non-EU countries. They have worked for 1-4,5 years in different
      German hospitals. RESULTS: Stressors and challenges derived from a lack in German
      language skills, different medical skills, cooperation in the team, and from
      dealing with a new health care system. Perceived discrimination by colleagues and
      patients represented a particular burden. In the meantime physicians with
      immigrant background disposed resources on different levels as on
      communicational, medical, social and organizational levels. DISCUSSION: The
      results highlight the particular demands that physicians with immigrant
      background face. Future research should explore potentials of stressors and
      resources for physicians with immigrant background by using quantitative methods;
      in terms of a multi-perspective approach German colleagues and patients should be
      included.

PMID- 29351713
TI  - [Living with Localized Prostate Cancer - Decision-Making and Coping with the
      Illness].
AB  - BACKGROUND: Men diagnosed with localized prostate cancer must make a choice
      between treatment strategies that differ considerably in their side effects and
      have different long-term requirements for coping with the disease. The aim of
      this study was to describe how men perceive their treatment decision
      retrospectively and which coping strategies they use. MATERIAL & METHODS: Fifteen
      men (age mean=67.13+/-9.38 years) diagnosed with localized prostate cancer
      participated in three focus groups, grouped according to the treatment strategies
      radical prostatectomy, radiotherapy, and active surveillance. An interview guide
      structured the focus group discussions. In analogy to the structured interview,
      the material was deductively sorted in a first step; in a second step, sub
      categories were developed inductively from the material. RESULTS: The content
      analysis revealed four particularly relevant topics: (1) The communication of the
      diagnosis and the associated reactions. (2) The decision-making process and the
      perceived time pressure. (3) The coping strategies, which showed a broad spectrum
      ranging from distraction and information search to lifestyle changes. (4) The
      perception of the disease over time. In particular men under active surveillance
      highlighted the importance of deceleration in their decision making and the role
      of lifestyle changes. DISCUSSION: The time of the diagnosis is still very much
      present even a long time after the diagnosis has been communicated. It is
      possible that a decrease in time pressure and deceleration would lead to more men
      deciding in favor of an observational strategy. Lifestyle changes could
      especially help men who choose active surveillance to overcome the feeling of
      "doing nothing" and gain a sense of control. CONCLUSION:  In view of the variety
      of possible treatment strategies, an ethic of action is required that meets the
      need for an individual and preference-sensitive decision.

PMID- 29351714
TI  - [Prevalence and Phenomenology of Psychotic-Like Symptoms in Borderline
      Personality Disorders - Associations with Suicide Attempts and Use of Psychiatric
      Inpatient Treatment].
AB  - BACKGROUND: Psychotic-like symptoms are found in a subgroup of borderline
      patients (BPD). Reported prevalence is heterogeneous (up to 50% affected).
      Investigations in Germany have not been conducted so far. Furthermore, the
      precise phenomenology of the psychotic symptoms and the effects on suicidal
      behavior and the use of inpatient psychiatric treatment are unclear. OBJECTIVES:
      The aim of the study was to investigate prevalence rates and phenomenology of
      psychotic-like symptoms. Associations between the latter and suicidality as well
      as the use of inpatient psychiatric treatment were examined. Further influencing
      factors were taking into account. METHODS: Psychotic-like symptoms were assessed
      with the Structured Clinical Interview-I in 95 BPD patients. To investigate the
      associations between psychotic-like symptoms and suicidality as well as the use
      of inpatient psychiatric treatment, correlation and regression analyzes were
      calculated, considering severity of PTSD, BPD and depression. RESULTS: 36% of the
      patients reported alterations of perception and 21% delusions, both multiform and
      long lasting. The number of suicide attempts was associated with delusions,
      alterations of perception and severity of PTSD, BPS, and depression. Only
      delusions and severity of PTSD explained together 25.8% of the variance for the
      prediction of the number of suicide attempts. Age of initial hospitalization
      showed fewer and number of hospitalizations no associations at all. DISCUSSION:
      Psychotic-like symptoms should not be trivialized, which may happen by using
      terms such as pseudo-hallucinations or transient paranoid ideas, and may be
      particularly associated with suicidal tendencies complicating the clinical
      course.

PMID- 29351715
TI  - The Impact of Migration Background on the Health Outcomes of Preschool Children:
      Linking a Cross-Sectional Survey to the School Entrance Health Examination
      Database in Bavaria, Germany.
AB  - AIM OF THE STUDY: This study investigated the impact of migration background on
      the health outcomes of preschool children from families of various social status
      levels. METHODS: During the school entrance health examination
      (Schuleingangsuntersuchung (SEU)) from October 2012 to August 2013, the parents
      of 5052 preschool children (62% response rate) participated in a cross-sectional
      health survey within the framework of health-monitoring units (Gesundheits
      Monitoring-Einheiten (GME)) in Bavaria, Germany. They were handed a self
      administered questionnaire with questions relating to the language spoken at home
      and other socio-demographic characteristics. By applying the record linkage
      method, 3747 participants were correctly linked to the corresponding data of the
      SEU. Based on the merged dataset, 4 definitions of migration background were
      explored regarding demographic indicators, the parents' mother tongue, and the
      language spoken at home. The association between migration background and health
      outcomes of preschool children was analyzed using multivariable logistic
      regression models separately. The risk estimates were presented for the study
      population and stratified into high, medium, and low social status. The models
      were repeated for each of the 4 migration background variables. RESULTS: The
      results show significant associations between migration background and health
      outcomes of preschool children (except in pronunciation). A migration background
      had the strongest impact on the development of word/sentence formation disorder.
      Compared to non-migrant preschool children, migrant children had twice the
      chances for full vaccination coverage (OR [95% CI]: 2.4 [1.9-3.1]) but only half
      the chance to participate in all health examinations from U1 to U9 (0.5 [0.4
      0.6]). These children were also at two-fold increased risk to be overweight/obese
      (2.2 [1.7-2.8]). Moreover, preschool children with double-sided migration from
      medium social status families faced the highest risk for word/sentence formation
      disorder (9.5 [5.6-16.1] with SEU definition and 23.3 [10.3-52.6] with GME
      definition of a migration background). CONCLUSIONS: Future prevention programs at
      the preschool level should focus on children with double-sided migration from
      medium social status families. With respect to social and cultural integration,
      the definition of migration background based on the language spoken at home
      should be appropriate for future SEUs.

PMID- 29351717
TI  - Prediction of Protein Configurational Entropy (Popcoen).
AB  - A knowledge-based method for configurational entropy prediction of proteins is
      presented; this methodology is extremely fast, compared to previous approaches,
      because it does not involve any type of configurational sampling. Instead, the
      configurational entropy of a query fold is estimated by evaluating an artificial
      neural network, which was trained on molecular-dynamics simulations of ~1000
      proteins. The predicted entropy can be incorporated into a large class of protein
      software based on cost-function minimization/evaluation, in which configurational
      entropy is currently neglected for performance reasons. Software of this type is
      used for all major protein tasks such as structure predictions, proteins design,
      NMR and X-ray refinement, docking, and mutation effect predictions. Integrating
      the predicted entropy can yield a significant accuracy increase as we show
      exemplarily for native-state identification with the prominent protein software
      FoldX. The method has been termed Popcoen for Prediction of Protein
      Configurational Entropy. An implementation is freely available at
      http://fmc.ub.edu/popcoen/ .

PMID- 29351716
TI  - Effect of metformin on glycaemic control in patients with type 1 diabetes: A meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: For type 1 diabetes (T1D) patients, adding metformin to insulin
      therapies is thought to improve blood glucose levels, but current evidence does
      not support this clinical benefit. Additional data from large clinical trials are
      now available; therefore, we conducted a meta-analysis of studies on assessing
      the efficacy and adverse effects of metformin. METHODS: We searched the MEDLINE,
      EMBASE, and Cochrane Library databases for data from randomized controlled
      trials. We performed statistical analyses by using Review Manager 5.2. RESULTS:
      Thirteen randomized controlled trials that compared metformin versus placebo met
      our inclusion criteria and were included in the study. The final meta-analysis
      included a total of 1183 participants with T1D. Metformin was associated with
      reductions in BMI (-1.14, 95% CI -2.05 to -0.24, P = .01), insulin requirements (
      0.47, 95% CI -0.70 to -0.23, P = .0001), total cholesterol (-0.23, 95% CI -0.34
      to -0.12, P < .0001), and low-density lipoprotein cholesterol (-0.20, 95% CI 
      0.29 to -0.11, P < .0001) in T1D patients. No clear evidence indicated that
      metformin improved HbA1c, triglyceride, or high-density lipoprotein cholesterol
      levels. A safety analysis showed that metformin slightly increased the risk of
      severe hypoglycaemia (1.23, 95% CI 1.00 to 1.52, P = .05) and mainly
      gastrointestinal adverse events (2.67, 95% CI 2.06 to 3.45, P < .00001). No
      evidence showed that metformin increased diabetic ketoacidosis events.
      CONCLUSIONS: Compared with placebo, metformin was not associated with glycaemic
      control in T1D patients. Although it exhibited other benefits, such as lower BMI
      and reduced insulin requirements, total cholesterol, and low-density lipoprotein
      cholesterol, negative outcomes, such as gastrointestinal adverse effects and
      severe hypoglycaemia, should also be considered in the use of metformin for T1D
      patients.

PMID- 29351718
TI  - "Good versus Good Enough?" Empirical Tests of Methane Leak Detection Sensitivity
      of a Commercial Infrared Camera.
AB  - Methane, a key component of natural gas, is a potent greenhouse gas. A key
      feature of recent methane mitigation policies is the use of periodic leak
      detection surveys, typically done with optical gas imaging (OGI) technologies.
      The most common OGI technology is an infrared camera. In this work, we
      experimentally develop detection probability curves for OGI-based methane leak
      detection under different environmental and imaging conditions. Controlled single
      blind leak detection tests show that the median detection limit (50% detection
      likelihood) for FLIR-camera based OGI technology is about 20 g CH4/h at an
      imaging distance of 6 m, an order of magnitude higher than previously reported
      estimates of 1.4 g CH4/h. Furthermore, we show that median and 90% detection
      likelihood limit follows a power-law relationship with imaging distance. Finally,
      we demonstrate that real-world marginal effectiveness of methane mitigation
      through periodic surveys approaches zero as leak detection sensitivity improves.
      For example, a median detection limit of 100 g CH4/h is sufficient to detect the
      maximum amount of leakage that is possible through periodic surveys. Policy
      makers should take note of these limits while designing equivalence metrics for
      next-generation leak detection technologies that can trade sensitivity for cost
      without affecting mitigation priorities.

PMID- 29351719
TI  - Synergistic and Antagonistic Interactions among the Particulate Matter Components
      in Generating Reactive Oxygen Species Based on the Dithiothreitol Assay.
AB  - We assessed the interactions among the particulate matter (PM) components in
      generating the reactive oxygen species (ROS) based on a dithiothreitol (DTT)
      assay. We started with the standard solutions of known redox-active substances,
      i.e., quinones (9,10-phenanthraquinone, 1,2-naphthoquinone, 1,4-naphthoquinone,
      and 5-hydroxy-1,4-naphthoquinone) and metals [Fe (II), Mn (II), and Cu (II)].
      Both DTT consumption and hydroxyl radical (.OH) generation were measured in the
      DTT assay. The interactions of Fe were additive with quinones in DTT consumption
      but strongly synergistic in .OH generation. Cu showed antagonistic interactions
      with quinones in both DTT consumption and .OH generation. Mn interacted
      synergistically with quinones in DTT oxidation but antagonistically in .OH
      generation. The nature of the interactions of these metals (Fe, Mn, and Cu) with
      ambient humic-like substances (HULIS) resembled that with quinones, although the
      intensity of interactions were weaker in DTT consumption than .OH generation.
      Finally, we demonstrated that the DTT consumption capability of ambient PM can be
      well explained by HULIS, three transition metals (Fe, Mn, and Cu), and their
      interactions, but .OH generation involves a contribution (~50%) from additional
      compounds (aliphatic species or metals other than Fe, Mn, and Cu) present in the
      hydrophilic PM fraction. The study highlights the need to account for the
      interactions between organic compounds and metals, while apportioning the
      relative contributions of chemical components in the PM oxidative potential.

PMID- 29351720
TI  - Structural Interconversion in Alzheimer's Amyloid-beta(16-35) Peptide in an
      Aqueous Solution.
AB  - Structural properties of Abeta(16-35) fragment are investigated as a model for
      the amyloid-beta peptide excluding its coil-inducing terminals. Our replica
      exchange molecular dynamics simulations using all-atom and explicit aqueous
      solvation widely reduce any structural bias. The principal folding pathway shows
      direct conversion of coil to beta-sheet, without the long proposed helix
      intermediates. Our principal component analysis indicates that the fragment is
      also intrinsically disordered, as the full amyloid-beta peptide. Thus, the
      observed folding mechanism lacks free-energy barriers and any peaks in the
      thermal capacity.

PMID- 29351721
TI  - Myeloperoxidase and Neurological Disorder: A Crosstalk.
AB  - Myeloperoxidase (MPO) is a protein present in azurophilic granules, macrophages,
      and neutrophils that are released into extracellular fluid (ECF) during
      inflammation. MPO releases hypochlorous acid (HOCl) and other chlorinated
      species. It is derived from hydrogen peroxide (H2O2) showing response during
      inflammatory conditions and plays a role in the immune defense against pathogens.
      MPO may show unwanted effects by indirectly increasing the formation of reactive
      nitrogen species (RNS), reactive oxygen species (ROS), and tumor necrosis factor
      alpha (TNF-alpha) leading to inflammation and oxidative stress. As
      neuroinflammation is one of the inevitable biological components among most of
      neurological disorders, MPO and its receptor may be explored as candidates for
      future clinical interventions. The purpose of this review is to provide an
      overview of the pathophysiological characteristics of MPO and further explore the
      possibilities to target it for clinical use. Targeting MPO is promising and may
      open an avenue to act as a biomarker for diagnosis with defined risk
      stratification in patients with various neurological disorders.

PMID- 29351722
TI  - Evaluation of matrix effects on TOF-SIMS data of leu-enkephalin and 1,2-dioleoyl
      sn-glycero-3-phosphocholine mixed samples.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is one of the most
      powerful methods to analyze biomolecules in biological tissues and cells because
      it provides detailed chemical structure information and chemical images with a
      high spatial resolution. However, in terms of quantitative analysis, there are
      issues such as matrix effects that often cause secondary ion intensity changes
      regardless of the actual concentration in a sample. For instance, the intensity
      of secondary ions related to peptides is generally suppressed when lipids
      coexist. Since the evaluation of biomolecules is crucial to understand biological
      phenomena, it is required to analyze peptides or lipids without matrix effects.
      Therefore, the mechanism of matrix effects regarding peptides and lipids in TOF
      SIMS was investigated in this study. Leu-enkephalin (YGGFL, molecular weight of
      555.3 Da) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC, C44H84NO8P,
      molecular weight 785.6 Da) were employed to prepare model samples. Model samples
      contain different weight ratios of these two molecules. The intensity of
      secondary ions related to the peptide or the lipid was compared with control
      samples containing pure leu-enkephalin or DOPC. As a result, it is indicated that
      the intensity of DOPC related secondary ions is strongly enhanced by coexisting
      leu-enkephalin, while the intensity of leu-enkephalin related secondary ions is
      suppressed by coexisting DOPC especially in a low concentration range of the
      peptide.

PMID- 29351724
TI  - The role of extracellular matrix components in angiogenesis and fibrosis:
      Possible implication for Systemic Sclerosis.
AB  - Extracellular matrix (ECM) plays a crucial role in the regulation of both
      physiological and pathological angiogenesis. ECM homeostasis and function is
      ensuring by the tightly regulation of the different ECM components including,
      collagens, proteoglycans and a variety of different glycoproteins. An altered
      expression of the above ECM molecules as well as an imbalance between the action
      of matrix remodeling enzymes and their tissue inhibitors is known to be
      responsible for impaired angiogenesis and fibrosis. Systemic Sclerosis (SSc) is
      an autoimmune disease characterized by micro-angiopathy, failure of reparative
      angiogenesis, and excessive fibrosis of the skin and various internal organs,
      dues to an increased production of ECM. A comprehensive search through
      Medline/PubMed and Scopus was performed for English-language original papers,
      using the keywords related to ECM components and SSc. This review will analyze
      the role played by ECM components in the deregulation of angiogenic mechanisms
      and in the persistence of a pro-fibrotic phenotype, during SSc. A better
      knowledge of these processes might provide information about molecules, which
      could be considered targets for future pro-angiogenic and/or anti-fibrotic
      therapies.

PMID- 29351725
TI  - Daylight-Mediated Photodynamic Therapy With Methyl Aminolevulinate in Actinic
      Keratosis Treatment.
AB  - BACKGROUND: Research has shown daylight-mediated photodynamic therapy (PDT) for
      the treatment of actinic keratosis (AK) to be effective, tolerable, and
      convenient, with excellent patient satisfaction and cosmesis. Although success
      has been demonstrated in areas with similar latitudes to Switzerland and
      Scandinavia, this treatment has not been studied in a Canadian population.
      OBJECTIVES: The purpose of this study is to investigate the effectiveness,
      safety, and patient satisfaction of daylight-mediated methyl 5-aminolevulinate
      (MAL)-PDT to make recommendations for its use in Canadian practice. METHODS: A
      retrospective chart review of patients who received treatment of daylight
      mediated MAL-PDT for the indication of AK at the Institute of Cosmetic and Laser
      Surgery in Oakville, Ontario, between 2009 and 2016. RESULTS: A total of 112
      patients were included, consisting of 94 males and 18 females with a mean age of
      63.79 years. A total of 177 sites were treated among all patients, mostly
      consisting of the face (n = 92) and scalp (n = 55). A total of 13.4% of patients
      experienced side effects, the most common being redness (n = 4) and scabbing (n =
      4). Of the 42 patients who expressed their level of satisfaction, 83.3% reported
      being happy with the treatment, chi2(1) = 18.67, P <= .05; 6.3% of patients were
      noted to be completely clear, 86.6% had a good response, 0.9% had a mild
      response, and 0% had no response, chi2(1) = 101.04, P <= .05. CONCLUSIONS:
      Daylight-mediated MAL-PDT is a suitable treatment option for AK lesions in a
      Canadian population due to the demonstrated efficacy, patient satisfaction,
      tolerability, and convenience.

PMID- 29351726
TI  - Paper Tools and Periodic Tables: Newlands and Mendeleev Draw Grids.
AB  - This essay elaborates on Ursula Klein's methodological concept of "paper tools"
      by drawing on several examples from the history of the periodic table. Moving
      from John A. R. Newlands's "Law of Octaves," to Dmitrii Mendeleev's first drafts
      of his periodic system in 1869, to Mendeleev's chemical speculations on the place
      of the ether within his classification, one sees that the ways in which the
      scientists presented the balance between empirical data and theoretical
      manipulation proved crucial for the chemical community's acceptance or rejection
      of their proposed innovations. This negotiated balance illustrates an
      underemphasised feature of Klein's conceptualisation of the ways in which a paper
      tool generates new knowledge.

PMID- 29351727
TI  - Report of a review of the induction and refresher scheme placement report tools.
AB  - GPs undertaking the Induction and Refresher (I&R) Scheme in England spend a
      period of between 4 weeks and 6 months in placements in a General Practice
      setting. During this time they have to complete a number of workplace-based
      assessments, and their Educational Supervisor is required to complete a report
      which confirms that they have demonstrated an adequate level of competence to
      enable them to be accepted by NHS England onto the National Medical Performers
      List without conditions. This report describes a process (using an online survey
      completed by Educational Supervisors) of reviewing and improving the end-of
      placement report forms to make them clearer and easier to use. The word pictures
      used in the revised forms could be adapted to become a competency framework for
      members of the primary care workforce.

PMID- 29351728
TI  - Corrigendum.

PMID- 29351729
TI  - The Brief Assessment of Family Functioning Scale (BAFFS): a three-item version of
      the General Functioning Scale of the Family Assessment Device.
AB  - The purpose of the present study is to compare results from the 12-item General
      Functioning Scale (GF-FAD) of the Family Assessment Device (FAD) to a three-item
      version, the Brief Assessment of Family Functioning Scale (BAFFS), designed to be
      used when brevity is especially important. We used principal components analysis
      of the GF-FAD, followed by multiple sample confirmatory factor analyses to test
      the robustness of the BAFFS in different samples. The BAFFS correlated highly
      with the GF-FAD, and demonstrated good concurrent validity with another measure
      of global marital functioning, the Dyadic Adjustment Scale-4 in a help-seeking
      sample. Like the 12-item version, the BAFFS moderately correlated with an
      objective, interview-based rating of family functioning, the McMaster Clinical
      Rating Scale. The BAFFS appears to serve as a good proxy for the GF-FAD when an
      ultra-brief family assessment measure is needed. Clinical or methodological
      significance of this article: This article introduces an ultra-brief measure of
      general family functioning that can easily be used in routine clinical practice.
      The measure can be used to track change over time, and to get a quick "snap shot"
      of how family members perceive the general emotional climate in their family.

PMID- 29351730
TI  - Population structure of Venturia inaequalis, a causal agent of apple scab, in
      response to heterogeneous apple tree cultivation.
AB  - BACKGROUND: Tracking newly emergent virulent populations in agroecosystems
      provides an opportunity to increase our understanding of the co-evolution
      dynamics of pathogens and their hosts. On the one hand host plants exert
      selective pressure on pathogen populations, thus dividing them into
      subpopulations of different virulence, while on the other hand they create an
      opportunity for secondary contact between the two divergent populations on one
      tree. The main objectives of the study were to explore whether the previously
      reported structure between two Venturia inaequalis population types, virulent or
      avirulent towards Malus x domestica cultivars carrying Rvi6 gene, is maintained
      or broken several years after the first emergence of new virulent strains in
      Poland, and to investigate the relationship between 'new' and 'native'
      populations derived from the same commercial orchards. For this purpose, we
      investigated the genetic structure of populations of the apple scab fungus,
      occurring on apple tree cultivars containing Rvi6, Rvi1 or Rvi17 resistance gene
      or no resistance at all, based on microsatellite data obtained from 606 strains
      sampled in 10 orchards composed of various host cultivars. RESULTS: Application
      of genetic distance inferring and clustering methods allowed us to observe clear
      genetic distinctness of the populations virulent towards cultivars carrying Rvi6
      gene from the Rvi6-avirulent populations and substructures within the Rvi6-group
      as a consequence of independent immigration events followed by rare, long
      distance dispersals. We did not observe such a structuring effect of other genes
      determining apple scab resistance on any other populations, which in turn were
      genetically homogenous. However, in two orchards the co-occurrence of strains of
      different virulence pattern on the same trees was detected, blurring the genetic
      boundaries between populations. CONCLUSIONS: Among several resistance genes
      studied, only Rvi6 exerted selective pressure on pathogens populations: those
      virulent toward Rvi6 hosts show unique and clear genetic and virulence pattern.
      For the first time in commercial Malus x domestica orchards, we reported
      secondary contacts between populations virulent and avirulent toward Rvi6 hosts.
      These two populations, first diverged in allopatry, second came into contact and
      subsequently began interbreeding, in such way that they show unambiguous
      footprints of gene flow today.

PMID- 29351723
TI  - Mitochondrial Uncoupling Proteins: Subtle Regulators of Cellular Redox Signaling.
AB  - SIGNIFICANCE: Mitochondria are the energetic, metabolic, redox, and information
      signaling centers of the cell. Substrate pressure, mitochondrial network
      dynamics, and cristae morphology state are integrated by the protonmotive force
      Deltap or its potential component, DeltaPsi, which are attenuated by proton
      backflux into the matrix, termed uncoupling. The mitochondrial uncoupling
      proteins (UCP1-5) play an eminent role in the regulation of each of the mentioned
      aspects, being involved in numerous physiological events including redox
      signaling. Recent Advances: UCP2 structure, including purine nucleotide and fatty
      acid (FA) binding sites, strongly support the FA cycling mechanism: UCP2 expels
      FA anions, whereas uncoupling is achieved by the membrane backflux of protonated
      FA. Nascent FAs, cleaved by phospholipases, are preferential. The resulting
      Deltap dissipation decreases superoxide formation dependent on Deltap. UCP
      mediated antioxidant protection and its impairment are expected to play a major
      role in cell physiology and pathology. Moreover, UCP2-mediated aspartate,
      oxaloacetate, and malate antiport with phosphate is expected to alter metabolism
      of cancer cells. CRITICAL ISSUES: A wide range of UCP antioxidant effects and
      participations in redox signaling have been reported; however, mechanisms of UCP
      activation are still debated. Switching off/on the UCP2 protonophoretic function
      might serve as redox signaling either by employing/releasing the extra capacity
      of cell antioxidant systems or by directly increasing/decreasing mitochondrial
      superoxide sources. Rapid UCP2 degradation, FA levels, elevation of purine
      nucleotides, decreased Mg2+, or increased pyruvate accumulation may initiate UCP
      mediated redox signaling. FUTURE DIRECTIONS: Issues such as UCP2 participation in
      glucose sensing, neuronal (synaptic) function, and immune cell activation should
      be elucidated. Antioxid. Redox Signal. 29, 667-714.

PMID- 29351732
TI  - Nutrient depletion and TOR inhibition induce 18S and 25S ribosomal RNAs resistant
      to a 5'-phosphate-dependent exonuclease in Candida albicans and other yeasts.
AB  - BACKGROUND: Messenger RNA (mRNA) represents a small percentage of RNAs in a cell,
      with ribosomal RNA (rRNA) making up the bulk of it. To isolate mRNA from
      eukaryotes, typically poly-A selection is carried out. Recently, a 5'-phosphate
      dependent, 5'->3' processive exonuclease called Terminator has become available.
      It will digest only RNA that has a 5'-monophosphate end and therefore it is very
      useful to eliminate most of rRNAs in cell. RESULTS: We have found that in the
      pathogenic yeast Candida albicans, while 18S and 25S components isolated from
      yeast in robust growth phase are easily eliminated by Terminator, those isolated
      from cells in the nutritionally diminished stationary phase, become resistant to
      digestion by this enzyme. Additional digestions with alkaline phosphatase,
      tobacco pyrophosphatase combined with Terminator point toward the 5'-prime end of
      18S and 25S as the source of this resistance. Inhibition of TOR by rapamycin also
      induces resistance by these molecules. We also find that these molecules are
      incorporated into the ribosome and are not just produced incidentally. Finally,
      we show that three other yeasts show the same behavior. CONCLUSIONS: Digestion of
      RNA by Terminator has revealed 18S and 25S rRNA molecules different from the
      accepted processed ones seen in ribosome generation. The reason for these
      molecules and the underlying mechanism for their formation is unknown. The
      preservation of this behavior across these yeasts suggests a useful biological
      role for it, worthy of further inquiry.

PMID- 29351731
TI  - A chelicerate-specific burst of nonclassical Dscam diversity.
AB  - BACKGROUND: The immunoglobulin (Ig) superfamily receptor Down syndrome cell
      adhesion molecule (Dscam) gene can generate tens of thousands of isoforms via
      alternative splicing, which is essential for both nervous and immune systems in
      insects. However, further information is required to develop a comprehensive view
      of Dscam diversification across the broad spectrum of Chelicerata clades, a basal
      branch of arthropods and the second largest group of terrestrial animals.
      RESULTS: In this study, a genome-wide comprehensive analysis of Dscam genes
      across Chelicerata species revealed a burst of nonclassical Dscams, categorised
      into four types-mDscam, sDscamalpha, sDscambeta, and sDscamgamma-based on their
      size and structure. Although the mDscam gene class includes the highest number of
      Dscam genes, the sDscam genes utilise alternative promoters to expand protein
      diversity. Furthermore, we indicated that the 5' cassette duplicate is inversely
      correlated with the sDscam gene duplicate. We showed differential and sDscam-
      biased expression of nonclassical Dscam isoforms. Thus, the Dscam isoform
      repertoire across Chelicerata is entirely dominated by the number and expression
      levels of nonclassical Dscams. Taken together, these data show that Chelicerata
      evolved a large conserved and lineage-specific repertoire of nonclassical Dscams.
      CONCLUSIONS: This study showed that arthropods have a large diversified
      Chelicerata-specific repertoire of nonclassical Dscam isoforms, which are
      structurally and mechanistically distinct from those of insects. These findings
      provide a global framework for the evolution of Dscam diversity in arthropods and
      offer mechanistic insights into the diversification of the clade-specific Ig
      superfamily repertoire.

PMID- 29351734
TI  - EOGD: the Euplotes octocarinatus genome database.
AB  - BACKGROUND: Euplotes, a ciliated protozoan, is a useful unicellular model
      organism. Studies on Euplotes have provided excellent insights into various basic
      biological principles. We have recently sequenced the macronuclear genome of the
      common freshwater species Euplotes octocarinatus to provide novel insights into
      Euplotes genetics and molecular biology. RESULTS: In this study, we present the
      E. octocarinatus Genome Database (EOGD), a functional annotation and analysis
      platform for the global study of the Euplotes genome. EOGD includes macronuclear
      genomic and transcriptomic data, predicted gene models, coding sequences, protein
      sequences, and functional annotations. The GBrowser and BLAST tools are embedded
      in EOGD to enable the search, visualization and analysis of E. octocarinatus
      genomic and transcriptomic data. CONCLUSIONS: EOGD is a useful resource for the
      research community, particularly for researchers who conduct genome-scale
      analysis and molecular biology studies of Euplotes or other ciliates. EOGD will
      be continuously updated to integrate more datasets and analytical tools. EOGD is
      freely available at http://ciliates.ihb.ac.cn/database/home/#eo .

PMID- 29351733
TI  - Glutamate synthases from conifers: gene structure and phylogenetic studies.
AB  - BACKGROUND: Plants synthesize glutamate from ammonium by the combined activity of
      the enzymes glutamine synthetase (GS) and glutamate synthase (GOGAT) through the
      glutamate synthase cycle. In plants, there are two forms of glutamate synthases
      that differ in their electron donors, NADH-GOGAT (EC 1.4.1.14) and Fd-GOGAT (EC
      1.4.7.1), which have differential roles either in primary ammonia assimilation or
      in the reassimilation of ammonium from different catabolic processes. Glutamate
      synthases are complex iron-sulfur flavoproteins containing functional domains
      involved in the control and coordination of their catalytic activities in annual
      plants. In conifers, partial cDNA sequences for GOGATs have been isolated and
      used for gene expression studies. However, knowledge of the gene structure and of
      phylogenetic relationships with other plant enzymes is quite scant. RESULTS:
      Technological advances in conifer megagenomes sequencing have made it possible to
      obtain full-length cDNA sequences encoding Fd- and NADH-GOGAT from maritime pine,
      as well as BAC clones containing sequences for NADH-GOGAT and Fd-GOGAT genes. In
      the current study, we studied the genomic organization of pine GOGAT genes, the
      size of their exons/introns, copy numbers in the pine genome and relationships
      with other plant genes. Phylogenetic analysis was performed, and the degree of
      preservation and dissimilarity of key domains for the catalytic activities of
      these enzymes in different taxa were determined. CONCLUSIONS: Fd- and NADH-GOGAT
      are encoded by single-copy genes in the maritime pine genome. The Fd-GOGAT gene
      is extremely large spanning more than 330 kb and the presence of very long
      introns highlights the important contribution of LTR retrotransposons to the gene
      size in conifers. In contrast, the structure of the NADH-GOGAT gene is similar to
      the orthologous genes in angiosperms. Our phylogenetic analysis indicates that
      these two genes had different origins during plant evolution. The results provide
      new insights into the structure and molecular evolution of these essential genes.

PMID- 29351735
TI  - Assessing the effect of a partly unobserved, exogenous, binary time-dependent
      covariate on survival probabilities using generalised pseudo-values.
AB  - BACKGROUND: Investigating the impact of a time-dependent intervention on the
      probability of long-term survival is statistically challenging. A typical example
      is stem-cell transplantation performed after successful donor identification from
      registered donors. Here, a suggested simple analysis based on the exogenous donor
      availability status according to registered donors would allow the estimation and
      comparison of survival probabilities. As donor search is usually ceased after a
      patient's event, donor availability status is incompletely observed, so that this
      simple comparison is not possible and the waiting time to donor identification
      needs to be addressed in the analysis to avoid bias. It is methodologically
      unclear, how to directly address cumulative long-term treatment effects without
      relying on proportional hazards while avoiding waiting time bias. METHODS: The
      pseudo-value regression technique is able to handle the first two issues; a novel
      generalisation of this technique also avoids waiting time bias. Inverse
      probability-of-censoring weighting is used to account for the partly unobserved
      exogenous covariate donor availability. RESULTS: Simulation studies demonstrate
      unbiasedness and satisfying coverage probabilities of the new method. A real data
      example demonstrates that study results based on generalised pseudo-values have a
      clear medical interpretation which supports the clinical decision making process.
      CONCLUSIONS: The proposed generalisation of the pseudo-value regression technique
      enables to compare survival probabilities between two independent groups where
      group membership becomes known over time and remains partly unknown. Hence,
      cumulative long-term treatment effects are directly addressed without relying on
      proportional hazards while avoiding waiting time bias.

PMID- 29351736
TI  - Studying medical communication with video vignettes: a randomized study on how
      variations in video-vignette introduction format and camera focus influence
      analogue patients' engagement.
AB  - BACKGROUND: Video vignettes are used to test the effects of physicians'
      communication on patient outcomes. Methodological choices in video-vignette
      development may have far-stretching consequences for participants' engagement
      with the video, and thus the ecological validity of this design. To supplement
      the scant evidence in this field, this study tested how variations in video
      vignette introduction format and camera focus influence participants' engagement
      with a video vignette showing a bad news consultation. METHODS: Introduction
      format (A = audiovisual vs. B = written) and camera focus (1 = the physician
      only, 2 = the physician and the patient at neutral moments alternately, 3 = the
      physician and the patient at emotional moments alternately) were varied in a
      randomized 2 * 3 between-subjects design. One hundred eighty-one students were
      randomly assigned to watch one of the six resulting video-vignette conditions as
      so-called analogue patients, i.e., they were instructed to imagine themselves
      being in the video patient's situation. Four dimensions of self-reported
      engagement were assessed retrospectively. Emotional engagement was additionally
      measured by recording participants' electrodermal and cardiovascular activity
      continuously while watching. Analyses of variance were used to test the effects
      of introduction format, camera focus and their interaction. RESULTS: The
      audiovisual introduction induced a stronger blood pressure response during
      watching the introduction (p = 0.048, [Formula: see text]= 0.05) and the
      consultation part of the vignette (p = 0.051, [Formula: see text]= 0.05), when
      compared to the written introduction. With respect to camera focus, results
      revealed that the variant focusing on the patient at emotional moments evoked a
      higher level of electrodermal activity (p = 0.003, [Formula: see text]= 0.06),
      when compared to the other two variants. Furthermore, an interaction effect was
      shown on self-reported emotional engagement (p = 0.045, [Formula: see text]=
      0.04): the physician-only variant resulted in lower emotional engagement if the
      vignette was preceded by the audiovisual introduction. No effects were shown on
      the other dimensions of self-reported engagement. CONCLUSIONS: Our findings imply
      that using an audiovisual introduction combined with alternating camera focus
      depicting patient's emotions results in the highest levels of emotional
      engagement in analogue patients. This evidence can inform methodological
      decisions during the development of video vignettes, and thereby enhance the
      ecological validity of future video-vignettes studies.

PMID- 29351737
TI  - Identifying genome-wide immune gene variation underlying infectious disease in
      wildlife populations - a next generation sequencing approach in the gopher
      tortoise.
AB  - BACKGROUND: Infectious disease is the single greatest threat to taxa such as
      amphibians (chytrid fungus), bats (white nose syndrome), Tasmanian devils (devil
      facial tumor disease), and black-footed ferrets (canine distemper virus, plague).
      Although understanding the genetic basis to disease susceptibility is important
      for the long-term persistence of these groups, most research has been limited to
      major-histocompatibility and Toll-like receptor genes. To better understand the
      genetic basis of infectious disease susceptibility in a species of conservation
      concern, we sequenced all known/predicted immune response genes (i.e., the
      immunomes) in 16 Florida gopher tortoises, Gopherus polyphemus. All tortoises
      produced antibodies against Mycoplasma agassizii (an etiologic agent of
      infectious upper respiratory tract disease; URTD) and, at the time of sampling,
      either had (n = 10) or lacked (n = 6) clinical signs. RESULTS: We found several
      variants associated with URTD clinical status in complement and lectin genes,
      which may play a role in Mycoplasma immunity. Thirty-five genes deviated from
      neutrality according to Tajima's D. These genes were enriched in functions
      relating to macromolecule and protein modifications, which are vital to immune
      system functioning. CONCLUSIONS: These results are suggestive of genetic
      differences that might contribute to disease severity, a finding that is
      consistent with other mycoplasmal diseases. This has implications for management
      because tortoises across their range may possess genetic variation associated
      with a more severe response to URTD. More generally: 1) this approach
      demonstrates that a broader consideration of immune genes is better able to
      identify important variants, and; 2) this data pipeline can be adopted to
      identify alleles associated with disease susceptibility or resistance in other
      taxa, and therefore provide information on a population's risk of succumbing to
      disease, inform translocations to increase genetic variation for disease
      resistance, and help to identify potential treatments.

PMID- 29351738
TI  - Oscillometric blood pressure by age and height for non overweight children and
      adolescents in Lubumbashi, Democratic Republic of Congo.
AB  - BACKGROUND: The diagnosis of hypertension in children is complex because based on
      normative values by sex, age and height, and these values vary depending on the
      environment. Available BP references used, because of the absence of local data,
      do not correspond to our pediatric population. Accordingly, our study aimed to
      provide the BP threshold for children and adolescents in Lubumbashi (DRC) and to
      compare them with German (KIGGS study), Polish (OLAF study) and Chinese (CHNS
      study) references. METHODS: We conducted a cross-sectional study among 7523
      school-children aged 3 to 17 years. The standardized BP measurements were
      obtained using a validated oscillometric device (Datascope Accutor Plus). After
      excluding overweight and obese subjects according to the IOTF definition (n =
      640), gender-specific SBP and DBP percentiles, which simultaneously accounted for
      age and height by using an extension of the LMS method, namely GAMLSS, were
      tabulated. RESULTS: The 50th, 90th and 95th percentiles of SBP and DBP for 3373
      boys and 3510 girls were tabulated simultaneously by age and height (5th, 25th,
      50th, 75th and 95th height percentile). Before 13 years the 50th and 90th
      percentiles of SBP for boys were higher compared with those of KIGGS and OLAF,
      and after they became lower: the difference for adolescents aged 17 years was
      respectively 8 mmHg (KIGGS) and 4 mmHg (OLAF). Concerning girls, the SBP 50th
      percentile was close to that of OLAF and KIGGS studies with differences that did
      not exceed 3 mmHg; whereas the 90th percentile of girls at different ages was
      high. Our oscillometric 50th and 90th percentiles of SBP and DBP were very high
      compared to referential ausculatory percentiles of the CHNS study respectively
      for boys from 8 to 14 mmHg and 7 to 13 mmHg; and for girls from 10 to 16 mmHg and
      11 to 16 mmHg. CONCLUSIONS: The proposed BP thresholds percentiles enable early
      detection and treatment of children and adolescents with high BP and develop a
      local program of health promotion in schools and family.

PMID- 29351739
TI  - A study of the association of rs12040273 with susceptibility and severity of
      coronary artery disease in a Chinese Han population.
AB  - BACKGROUND: The single nucleotide polymorphism (SNP) rs12040273, a variant of UDP
      N-acetylgalactosamine, polypeptide GalNAc-transferase 2, has recently been
      reported to be significantly associated with development of carotid artery intima
      media thickness (IMT) in a Chinese population based on a genome-wide association
      study. Because IMT is a potent marker of coronary artery disease (CAD), the aim
      of this study was to evaluate the relation of rs12040273 to susceptibility and
      severity of CAD in a Chinese Han population. METHODS: We performed a hospital
      based case-control study. Three hundred and thirty-one individuals (199 CAD
      patients and 112 non-CAD controls) undergoing coronary angiography were
      consecutively enrolled in the study. The Gensini score results were used to
      assess the severity of CAD. The method of polymerase chain reaction-ligase
      detection reaction (PCR-LDR) was used to distinguish different genotypes at
      rs12040273. RESULTS: The distribution of genotypes at rs12040273 was comparable
      between CAD patients and non-CAD controls (P > 0.05). The frequencies of the
      genotypes were also not significantly associated with the risk of CAD and its
      severity assessed by the Gensini score method, with the OR of 1.38 (95% CI = 0.80
      2.40, P = 0.24) and 1.14 (95% CI = 0.69-1.86, P = 0.60) respectively. However,
      stratified analysis showed that the serum HDL-C levels of subjects with the CC
      genotype were significantly higher than those with CT/TT genotypes in non-CAD
      controls (P = 0.002). CONCLUSION: Our results suggest that the rs12040273
      variants might not be associated with the susceptibility of CAD or its severity
      in a Chinese Han population. Moreover, the CC genotype could be associated with
      elevated serum HDL-C levels.

PMID- 29351740
TI  - Population size may shape the accumulation of functional mutations following
      domestication.
AB  - BACKGROUND: Population genetics theory predicts an important role of differences
      in the effective population size (N e ) among species on shaping the accumulation
      of functional mutations by regulating the selection efficiency. However, this
      correlation has never been tested in domesticated animals. RESULTS: Here, we
      synthesized 62 whole genome data in eight domesticated species (cat, dog, pig,
      goat, sheep, chicken, cattle and horse) and compared domesticates with their wild
      (or ancient) relatives. Genes with significantly different selection pressures
      (revealed by nonsynonymous/synonymous substitution rate ratios, Ka/Ks or omega)
      between domesticated (Domega) and wild animals (Womega) were determined by
      likelihood-ratio tests. Species-level effective population sizes (N e ) were
      evaluated by the pairwise sequentially Markovian coalescent (PSMC) model, and
      Domega/Womega were calculated for each species to evaluate the changes in
      accumulation of functional mutations after domestication relative to pre
      domestication period. Correlation analysis revealed that the most recent (~
      10.000 years ago) N e (s) are positively correlated with Domega/Womega. This
      result is consistent with the corollary of the nearly neutral theory, that higher
      N e could boost the efficiency of positive selection, which might facilitate the
      overall accumulation of functional mutations. In addition, we also evaluated the
      accumulation of radical and conservative mutations during the domestication
      transition as: Dradical/Wradical and Dconservative/Wconservative, respectively.
      Surprisingly, only Dradical/Wradical ratio exhibited a positive correlation with
      N e (p < 0.05), suggesting that domestication process might magnify the
      accumulation of radical mutations in species with larger N e . CONCLUSIONS: Our
      results confirm the classical population genetics theory prediction and highlight
      the important role of species' N e in shaping the patterns of accumulation of
      functional mutations, especially radical mutations, in domesticated animals. The
      results aid our understanding of the mechanisms underlying the accumulation of
      functional mutations after domestication, which is critical for understanding the
      phenotypic diversification associated with this process.

PMID- 29351741
TI  - Risk factors for Mycobacterium ulcerans infection (Buruli Ulcer) in Togo ? a case
      control study in Zio and Yoto districts of the maritime region.
AB  - BACKGROUND: Buruli ulcer (BU) is a neglected mycobacterial skin infection caused
      by Mycobacterium ulcerans. This disease mostly affects poor rural populations,
      especially in areas with low hygiene standards and sanitation coverage. The
      objective of this study was to identify these risk factors in the districts of
      Zio and Yoto of the Maritime Region in Togo. METHODS: We conducted a case-control
      study in Zio and Yoto, two districts proved BU endemic from November 2014 to May
      2015. BU cases were diagnosed according to the WHO clinical case definition at
      the Centre Hospitalier Regional de Tsevie (CHR Tsevie) and confirmed by Ziehl
      Neelsen (ZN) microscopy and IS2404 polymerase chain reaction (PCR). For each
      case, up to two controls matched by sex and place of residence were recruited.
      Socio-demographic, environmental or behavioral data were collected and
      conditional logistic regression analysis was used to identify and compare risk
      factors between BU cases and controls. RESULTS: A total of 83 cases and 128
      controls were enrolled. The median age was 15 years (range 3-65 years).
      Multivariate conditional logistic regression analysis after adjustment for
      potential confounders identified age (< 10 years (OR =11.48, 95% CI = 3.72-35.43)
      and 10-14 years (OR = 3.63, 95% CI = 1.22-10.83)), receiving insect bites near a
      river (OR = 7.8, 95% CI = 1.48-41.21) and bathing with water from open borehole
      (OR = 5.77, (1.11-29.27)) as independent predictors of acquiring BU infection.
      CONCLUSIONS: This study identified age, bathing with water from open borehole and
      receiving insect bites near a river as potential risk of acquiring BU infection
      in Zio and Yoto districts of the Maritime Region in south Togo.

PMID- 29351742
TI  - HERV-W group evolutionary history in non-human primates: characterization of ERV
      W orthologs in Catarrhini and related ERV groups in Platyrrhini.
AB  - BACKGROUND: The genomes of all vertebrates harbor remnants of ancient retroviral
      infections, having affected the germ line cells during the last 100 million
      years. These sequences, named Endogenous Retroviruses (ERVs), have been
      transmitted to the offspring in a Mendelian way, being relatively stable
      components of the host genome even long after their exogenous counterparts went
      extinct. Among human ERVs (HERVs), the HERV-W group is of particular interest for
      our physiology and pathology. A HERV-W provirus in locus 7q21.2 has been coopted
      during evolution to exert an essential role in placenta, and the group expression
      has been tentatively linked to Multiple Sclerosis and other diseases. Following
      up on a detailed analysis of 213 HERV-W insertions in the human genome, we now
      investigated the ERV-W group genomic spread within primate lineages. RESULTS: We
      analyzed HERV-W orthologous loci in the genome sequences of 12 non-human primate
      species belonging to Simiiformes (parvorders Catarrhini and Platyrrhini),
      Tarsiiformes and to the most primitive Prosimians. Analysis of HERV-W orthologous
      loci in non-human Catarrhini primates revealed species-specific insertions in the
      genomes of Chimpanzee (3), Gorilla (4), Orangutan (6), Gibbon (2) and especially
      Rhesus Macaque (66). Such sequences were acquired in a retroviral fashion and, in
      the majority of cases, by L1-mediated formation of processed pseudogenes. There
      were also a number of LTR-LTR homologous recombination events that occurred
      subsequent to separation of Catarrhini sub-lineages. Moreover, we retrieved 130
      sequences in Marmoset and Squirrel Monkeys (family Cebidae, Platyrrhini
      parvorder), identified as ERV1-1_CJa based on RepBase annotations, which appear
      closely related to the ERV-W group. Such sequences were also identified in
      Atelidae and Pitheciidae, representative of the other Platyrrhini families. In
      contrast, no ERV-W-related sequences were found in genome sequence assemblies of
      Tarsiiformes and Prosimians. CONCLUSIONS: Overall, our analysis now provides a
      detailed picture of the ERV-W sequences colonization of the primate lineages
      genomes, revealing the exact dynamics of ERV-W locus formations as well as novel
      insights into the evolution and origin of the group.

PMID- 29351743
TI  - Phosphate signaling through alternate conformations of the PstSCAB phosphate
      transporter.
AB  - BACKGROUND: Phosphate is an essential compound for life. Escherichia coli employs
      a signal transduction pathway that controls the expression of genes that are
      required for the high-affinity acquisition of phosphate and the utilization of
      alternate sources of phosphorous. These genes are only expressed when
      environmental phosphate is limiting. The seven genes for this signaling pathway
      encode the two-component regulatory proteins PhoB and PhoR, as well as the high
      affinity phosphate transporter PstSCAB and an auxiliary protein called PhoU. As
      the sensor kinase PhoR has no periplasmic sensory domain, the mechanism by which
      these cells sense environmental phosphate is not known. This paper explores the
      hypothesis that it is the alternating conformations of the PstSCAB transporter
      which are formed as part of the normal phosphate transport cycle that signal
      phosphate sufficiency or phosphate limitation. RESULTS: We tested two variants of
      PstB that are predicted to lock the protein in either of two conformations for
      their signaling output. We observed that the pstBQ160K mutant, predicted to
      reside in an inward-facing, open conformation signaled phosphate sufficiency
      whereas the pstBE179Q mutant, predicted to reside in an outward-facing, closed
      conformation signaled phosphate starvation. Neither mutant showed phosphate
      transport. CONCLUSIONS: These results support the hypothesis that the alternating
      conformations of the PstSCAB transporter are sensed by PhoR and PhoU. This
      sensory mechanism thus controls the alternate autokinase and phospho-PhoB
      phosphatase activities of PhoR, which ultimately control the signaling state of
      the response regulator PhoB.

PMID- 29351744
TI  - Risk factors for first-time acute myocardial infarction patients in Trinidad.
AB  - BACKGROUND: The relative importance of coronary artery disease (CAD) risk varies
      globally. The aim of this study was to determine CAD risk factors for acute
      myocardial infarction (AMI) among patients in public health care institutions in
      Trinidad using a case-control type study design. METHODS: The sample comprised
      251 AMI patients hospitalized between March 1, 2011 and April 30, 2012 and 464
      age- and sex-matched non-AMI patients with no terminal or life-threatening
      illness and who did not undergo treatment for CAD. SPSS version 19 was used for
      data analysis that included chi-square tests, unadjusted and adjusted odds ratios
      (OR) and conditional multiple binary logistic regression. RESULTS: There was no
      difference in age between AMI and non-AMI patients (p = 0.551). Chi-square test
      revealed that clinical and lifestyle variables including stressful life,
      diabetes, hypertension, hypercholesterolaemia, ischaemic heart disease (IHD), a
      family history of IHD (p <= 0.001), smoking (p = 0.007) and alcohol consumption
      (p = 0.013) were associated with AMI; sex (p = 0.441), ethnicity (p = 0.366), age
      group (p = 0.826) and renal failure (p = 0.487) were not. Both unadjusted and
      adjusted (for age) ORs showed that the odds of hypertension, IHD and alcohol
      consumption were greater among AMI patients than among non-AMI patients for
      males; diabetes and IHD for females; and that the odds of a stressful life was
      greater among non-AMI patients and were the same for both groups with respect to
      sex, age > 45 years, hypercholesterolemia, renal insufficiency, and family
      history of IHD. Conditional multiple logistic regression showed that smoking [OR:
      0.274, p <= 0.001, 95% CI for OR (0.140, 0.537)], a stressful life [OR: 2.697, p
      <= 0.001, 95% CI for OR (1.585, 4.587)], diabetes [OR: 0.530, p = 0.020, 95% CI
      for OR (0.310, 0.905)], hypertension [OR: 0.48, p = 0.10. 95% CI for OR (0.275,
      0.837)] and IHD [OR: 0.111, p <= 0.001, 95% CI for OR (0.057, 0.218)] were the
      only useful AMI predictors. CONCLUSIONS: Smoking, diabetes, hypertension, IHD and
      decrease stress are useful AMI predictors.

PMID- 29351746
TI  - Concomitant glenohumeral injuries in Neer type II distal clavicle fractures.
AB  - BACKGROUND: To identify the prevalence of concomitant glenohumeral injuries in
      surgically treated Neer type II distal clavicle fractures and relate its clinical
      importance. METHODS: Between 11/2011 and 11/2015 41 patients, suffering from a
      displaced and unstable distal clavicle fracture were included. 20 patients (group
      1) received surgical treatment by means of plate osteosynthesis in combination
      with an arthroscopically assisted coraco-clavicular ligament augmentation. In
      group 2 (n = 21 patients) the fracture was treated by hooked plating solely, and
      diagnostic arthroscopy was conducted during hardware retrieval after the fracture
      had healed. All arthroscopies were performed in a standardized fashion, images
      were blinded retrospectively, and evaluated by two independent investigators.
      RESULTS: In total, concomitant glenohumeral pathologies were found in 26.8% of
      cases (41 patients, mean age 43.6 +/- 16.6 years). In Group 1 (n = 20,
      arthroscopically assisted fracture treatment) the prevalence was 25%, in Group 2
      (n = 21, diagnostic arthroscopy during implant removal) 28.5% (p = 0.75).
      Concomitant glenohumeral injuries included Labrum- and SLAP-tears, partial and
      full thickness rotator cuff tears as well as lesions to the biceps pulley system.
      Concomitant injuries were addressed in 2 patients of group 1 (10%, 2* labrum
      repair) and in 3 patients of group 2 (14.3%, of Group 2 (2* arthroscopic cuff
      repair of full thickness tear, 1* subpectoral biceps tenodesis in an type IV SLAP
      lesion, p = 0.68). CONCLUSION: The present study could clarify the acute and for
      the first time mid-term implication and clinical relevance of concomitant
      glenohumeral injuries. They have been observed in averaged 27% of Neer type II
      distal clavicle fractures at these two times. However, the findings of this study
      show that not all concomitant lesions remain symptomatic. While lesions are still
      present after fracture healing, it's treatment may be depicted upon symptoms at
      the time of implant removal. In turn, early diagnosis and treatment of
      concomitant injuries seems reasonable, as untreated injuries can remain
      symptomatic for more than 6 months after the fracture and recovery may be
      delayed.

PMID- 29351745
TI  - The associations between weight-related anthropometrics during childhood and lung
      function in late childhood: a retrospective cohort study.
AB  - BACKGROUND: An association between body weight in childhood and subsequent lung
      function and asthma has been suggested, but few longitudinal studies exist. Our
      aim was to explore whether weight-related anthropometric measurements through
      childhood were associated with lung function in late childhood. METHODS: From an
      original nested case-control study, a cohort study was conducted, where lung
      function was measured in 463 children aged 12.8 years, and anthropometry was
      measured at several ages from birth through 12.8 years of age. Associations
      between anthropometrics and lung function were analysed using multiple linear and
      fractional polynomial regression analysis. RESULTS: Birthweight and body mass
      index (BMI; kg/m2) at different ages through childhood were positively associated
      with forced vital capacity in percent of predicted (FVC %) and forced expiratory
      volume in the first second in percent of predicted (FEV1%) at 12.8 years of age.
      BMI, waist circumference, waist-to-height ratio and skinfolds at 12.8 years of
      age and the change in BMI from early to late childhood were positively associated
      with FVC % and FEV1% and negatively associated with FEV1/FVC and forced
      expiratory flow at 25-75% of FVC/FVC. Interaction analyses showed that positive
      associations between anthropometrics other than BMI and lung function were mainly
      found in girls. Inverse U-shaped associations were found between BMI at the ages
      of 10.8/11.8 (girls/boys) and 12.8 years (both genders) and FVC % and FEV1% at
      12.8 years of age. CONCLUSIONS: Weight-related anthropometrics through childhood
      may influence lung function in late childhood. These findings may be
      physiological or associated with air flow limitation. Inverse U-shaped
      associations suggest a differential impact on lung function in normal-weight and
      overweight children. TRIAL REGISTRATION: This study was observational without any
      health care intervention for the participants. Therefore, no trial registration
      number is available.

PMID- 29351747
TI  - Combination of Pelargonium sidoides and Coptis chinensis root inhibits nuclear
      factor kappa B-mediated inflammatory response in vitro and in vivo.
AB  - BACKGROUND: Pelargonium sidoides (PS) and Coptis chinensis root (CR) have
      traditionally been used to treat various diseases, including respiratory and
      gastrointestinal infections, dysmenorrhea, and hepatic disorders. The present
      study was conducted to evaluate the anti-inflammatory effects of a combination of
      PS and CR in vitro and in vivo. METHODS: The in vitro effects of PS + CR on the
      induction of inflammation-related proteins were evaluated in lipopolysaccharide
      (LPS)-stimulated RAW 264.7 cells. The levels of nitric oxide (NO) and of
      inflammatory cytokines and prostaglandin E2 (PGE2) were measured using the Griess
      reagent and enzyme-linked immunosorbent assay (ELISA) methods, respectively. The
      expression of inflammation-related proteins was confirmed by Western blot.
      Additionally, the effects of PS + CR on paw edema volume, skin thickness, and
      numbers of infiltrated inflammatory cells, mast cells, COX-2-, iNOS-, and TNF
      alpha-immunoreactive cells in dorsum and ventrum pedis skin were evaluated in a
      rat model of carrageenan (CA)-induced paw edema. RESULTS: PS + CR significantly
      reduced production of NO, PGE2 and three pro-inflammatory cytokines (tumor
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6) and also
      decreased levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
      (COX-2). Treatment with PS + CR significantly reduced the protein expression
      levels of LPS-stimulated nuclear factor kappa B (NF-kappaB) and phosphorylated
      inhibitor of NF-kappaB (p-I-kappaBalpha). Additionally, PS + CR significantly
      inhibited the increases in paw swelling, skin thickness, infiltrated inflammatory
      cells, mast cell degranulation, COX-2-, iNOS-, and TNF-alpha-immunoreactive cells
      in the rat model of CA-induced acute edematous paw. CONCLUSIONS: These results
      demonstrate that PS + CR exhibits anti-inflammatory properties through decreasing
      the production of pro-inflammatory mediators (NO, PGE2, TNF-alpha, IL-1beta, and
      IL-6), suppressing NF-kappaB signaling in LPS-induced RAW 264.7 cells.
      Additionally, the results of the CA-induced rat paw edema assay revealed an anti
      edema effect of PS + CR. Furthermore, it is suggested that PS + CR also inhibits
      acute edematous inflammation by suppressing mast cell degranulation and
      inflammatory mediators (COX-2, iNOS, and TNF-alpha). Thus, PS + CR may be a
      potential candidate for the treatment of various inflammatory diseases, and it
      may also contribute to a better understanding of the molecular mechanisms
      underlying inflammatory response regulation.

PMID- 29351748
TI  - A comparative study of three conservative treatments in patients with lumbar
      spinal stenosis: lumbar spinal stenosis with acupuncture and physical therapy
      study (LAP study).
AB  - BACKGROUND: Although the efficiency of conservative management for lumbar spinal
      stenosis (LSS) has been examined, different conservative management approaches
      have not been compared. We have performed the first comparative trial of three
      types of conservative management (medication with acetaminophen, exercise, and
      acupuncture) in Japanese patients with LSS. METHODS: Patients with L5 root
      radiculopathy associated with LSS who visited our hospital for surgical treatment
      were enrolled between December 2011 and January 2014. In this open-label study,
      patients were assigned to three treatment groups (medication, exercise,
      acupuncture) according to the visit time. The primary outcomes were Zurich
      claudication questionnaire (ZCQ) scores before and after 4 weeks of treatment.
      Least square mean analysis was used to assess the following dependent variables
      in the treatment groups: changes in symptom severity and physical function scores
      of the ZCQ and the ZCQ score of patient's satisfaction after treatment. RESULTS:
      Thirty-eight, 40, and 41 patients were allocated to the medication, exercise, and
      acupuncture groups, respectively. No patient underwent surgical treatment during
      the study period. The symptom severity scores of the ZCQ improved significantly
      after treatment in the medication (p = 0.048), exercise (p = 0.003), and
      acupuncture (p = 0.04) groups. The physical function score improved significantly
      in the acupuncture group (p = 0.045) but not in the medication (p = 0.20) and
      exercise (p = 0.29) groups. The mean reduction in the ZCQ score for physical
      function was significantly greater for acupuncture than for exercise. The mean
      ZCQ score for treatment satisfaction was significantly greater for acupuncture
      than for medication. CONCLUSIONS: Acupuncture was significantly more effective
      than physical exercise according to the physical function score of the ZCQ and
      than medication according to the satisfaction score. The present study provides
      new important information that will aid decision making in LSS treatment. TRIAL
      REGISTRATION: This study was registered with the UMIN Clinical Trials Registry (
      UMIN000006957 ).

PMID- 29351749
TI  - Meta-analysis of serum C-reactive protein and cartilage oligomeric matrix protein
      levels as biomarkers for clinical knee osteoarthritis.
AB  - BACKGROUND: The roles of C-reactive protein (CRP) and cartilage oligomeric matrix
      protein (COMP) in knee osteoarthritis (KOA) remain controversial, thus the
      present study is aimed to explore the relationships between CRP, COMP, and the
      incidence/progression of KOA. METHODS: A systematic search was conducted on
      PubMed and Embase until September, 2016 for all the relevant studies. The pooled
      mean difference (MD) with its 95% confidence interval (95% CI) based on fixed
      effects model or random effects model was calculated to assess the potential role
      of CRP and COMP in the incidence or progression of KOA. Heterogeneity was
      evaluated by Cochran's Q and I2 tests. When P < 0.05 or I2 > 50%, a random
      effects model was chosen, otherwise, a fixed effects model was used. Moreover,
      the role of CRP in different degrees of pain was also analyzed. Sensitivity
      analysis was performed to evaluate the strength of the meta-analysis. RESULTS:
      Fourteen studies were enrolled in the meta-analysis. No difference was found
      between baseline CRP and CRP levels in the last follow-up period of KOA (MD = -
      0.09, 95% CI: -0.30, 0.13). Pooled data showed higher CRP concentration in
      patients with incident KOA when compared with controls (MD = 0.33, 95% CI: 0.04,
      0.63). Moreover, higher serum COMP levels were found in patients with incident
      KOA (MD = 1.69, 95% CI: 0.61, 2.76) Additionally, significant higher CRP
      concentration was observed in KOA patients with highest degree of pain (MD =
      1.60, 95% CI: 0.52, 2.67). CONCLUSION: CRP and COMP serum levels were both
      associated with the incidence of KOA. Patients with a higher CRP and COMP
      concentration might have an increased probability of developing KOA. However,
      higher CRP serum levels was not related with KOA progression. Furthermore, KOA
      patients with more pain had higher CRP concentrations.

PMID- 29351750
TI  - Associations of land, cattle and food security with infant feeding practices
      among a rural population living in Manyara, Tanzania.
AB  - BACKGROUND: Livelihoods strategies and food security experiences can positively
      and negatively affect infant and young child feeding (IYCF) practices. This study
      contributes to this literature by exploring how variation in household economics
      among rural farmers in Tanzania relates to IYCF patterns over the first 8 months
      of an infant's life. METHODS: These data were produced from a longitudinal study
      in which a cohort of mother-infant dyads was followed from birth to 24 months. In
      addition to baseline maternal, infant, and household characteristics, mothers
      were queried twice weekly and monthly about infant feeding practices and diet.
      Weekly and monthly datasets were merged and analyzed to assess infant feeding
      patterns through the first 8 months. Standard statistical methods including
      survival and logistic regression analyses were used. RESULTS: Aside from
      breastfeeding initiation, all other IYCF practices were suboptimal in this
      cohort. Land and cattle ownership were associated with the early introduction of
      non-breastmilk food items. Food insecurity also played a role in patterning and
      inadequate complementary feeding was commonplace. CONCLUSIONS: Health promotion
      programs are needed to delay the introduction of animal milks and grain-based
      porridge, and to achieve a minimum acceptable diet after 6 months of age among
      smallholder farmers in rural Tanzania. Results highlight that livelihoods-based
      health promotion interventions, built from a flexible and integrated design, may
      be an important strategy to address community-level variation in infant feeding
      practices and promote optimal IYCF practices.

PMID- 29351751
TI  - Social determinants of male health: a case study of Leeds, UK.
AB  - BACKGROUND: The social determinants of health have a disproportionate impact on
      mortality in men. A study into the state of health of the male population in
      Leeds was undertaken to guide public health commissioning decisions. This paper
      reports on the data relating to the social lives of men. METHODS: A cross
      sectional study was undertaken, comprising descriptive analysis of data relating
      to educational attainment, housing, employment (including benefit claimants),
      marital status and relationships. Data was considered for the whole city and
      localised at the Middle Super Output Area (MSOA) level and mapped against the
      Index of Deprivation. RESULTS: Boys' educational attainment was found to be
      lagging behind girls' from their earliest assessments (Early Years Foundation
      Stage Profile, 46% vs. 60%, P = 0.00) to GCSEs (53% vs. 63%, P = 0.00), leaving
      many men with no qualifications. There were 68% more men than women identified as
      being unemployed, with more men claiming benefits. Men living in social housing
      are more likely to be housed in high-rise flats. Almost 50% of men aged 16-64 are
      single, with 2254 lone fathers. CONCLUSIONS: There appears to be a lack of
      sex/gender analysis of current cross city data. In areas of deprivation a complex
      picture of multiple social problems emerges, with marked gender differences in
      the social determinants of health, with males seeming to be more negatively
      affected. There is a need for more focused planning for reaching out and
      targeting boys and men in the most deprived inner city areas, so that greater
      efficiency in service delivery can be obtained.

PMID- 29351752
TI  - Prevalence of gingivitis and calculus in 12-year-old Puerto Ricans: a cross
      sectional study.
AB  - BACKGROUND: Gingivitis is a common oral health problem. Untreated gingivitis may
      progress to periodontitis, a common cause of tooth loss. The prevalence of
      gingivitis and calculus among Puerto Rican children is unknown. Understanding
      this prevalence can support early public health preventative strategies. This
      study aims to estimate the prevalence of gingivitis and calculus among 12-year
      old Puerto Ricans by health region and to explore differences in distribution by
      school type (proxy for socio-economic status) and gender. METHODS: A probability
      based sample of 113 schools was selected proportional to enrollment size and
      stratified by health region, school type, and gender. Two trained examiners
      evaluated the presence of gingivitis and both supragingival and subgingival
      dental calculus. Gingivitis was defined as the presence of gingival bleeding upon
      gentle probing (BOP) in at least one site, and the extent of the problem was
      classified according to the percentage of teeth whose gingiva presented BOP
      (limited: 25-49% of the teeth tested; extensive: >50% of teeth tested). Logistic
      and linear regression models, adjusted for health regions, were used to compare
      gingivitis and calculus prevalence and extent between genders and school types.
      RESULTS: Gingivitis was found in 80.41% of the 1586 children evaluated. Urban
      public schoolchildren had a slightly higher prevalence (83.24%) compared to
      private (79.15%, p = 0.16); those in rural-public (77.59%) and private schools
      had similar prevalence (p = 0.15). Extensive gingivitis was present in 60.81% of
      all children. The mean percentage of sites presenting BOP (BOP%) was 17.79%.
      Rural and urban public schoolchildren presented significantly higher BOP%
      compared to children from private schools (p = 0.0005, p = 0.002, respectively).
      Dental calculus was detected in 61.59% of the sample, boys presenting
      significantly higher (p = 0.005) total and supragingival calculus. Rural-public
      schoolchildren had a significantly higher prevalence of subgingival calculus
      compared to private schoolchildren (p = 0.02). CONCLUSIONS: Gingivitis prevalence
      is higher among 12-year-old Puerto Ricans compared to data reported for U.S.
      adolescents. Public schoolchildren presented significantly higher BOP% sites
      compared to private schoolchildren. Boys presented a significantly higher total
      and supragingival calculus prevalence than girls. Oral health disparities related
      to gender and school type were identified by this study. Studies exploring the
      reasons for these disparities are recommended.

PMID- 29351753
TI  - Mesenchymal stem cells show functional defect and decreased anti-cancer effect
      after exposure to chemotherapeutic drugs.
AB  - BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic
      applications to improve the functions of bone, cardiac, nervous tissue as well as
      to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the
      non-hematopoietic stromal cells of the bone marrow and are important for the
      maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of
      leukemia extensively damage the stromal cells and alter their gene expression
      profiles. METHODS: We determined the changes in adipogenic, osteogenic
      differentiation, phenotypic and gene expression in MSC during treatment with
      chemotherapeutic drugs cytarabine, daunorubicin and vincristine. We also tested
      anti-cancer effects of drug treated MSC on leukemia cells. RESULTS: Treatment
      with the chemotherapeutic drugs resulted in functional defects in MSC, leading to
      reduced proliferation, osteogenic and adipogenic differentiation. The drug
      treated MSC also showed decreased expression of cell surface receptors, and the
      changes in proliferation, phenotype and differentiation defect was partially
      reversible after withdrawing the drugs from the cells. The drug treated MSC
      showed increased expression of cytokines, IL6, FGF2 and TNFA but reduced levels
      of differentiation markers SOX9 and ACTC1. Drug treated MSC also contributed to
      reduced anti-cancer effects in leukemia cells. CONCLUSIONS: Chemotherapeutic drug
      treatment altered the phenotype, osteogenic and adipogenic differentiation
      potential of MSC and modified the gene expression profile of the cells to render
      them more chemoprotective of the leukemic cells. Thus, additional therapeutic
      efforts to target the stromal cell population will help in preventing
      chemoresistance, disease relapse in leukemia and to maintain a healthy bone
      marrow stroma.

PMID- 29351754
TI  - Chronic airflow obstruction in Tanzania - a cross-sectional study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease is a global problem and
      available data from sub-Saharan Africa is very limited. METHODS: A cross
      sectional facility-based pilot study among patients and visitors to an urban and
      a rural primary healthcare facility was conducted in coastal Tanzania. The
      primary outcome was the prevalence of chronic airflow obstruction. RESULTS: The
      final analysis included 598 participants with valid post-bronchodilator
      spirometry. Applying ATS/ERS spirometric criteria, chronic airflow obstruction
      was found in n = 24 (4%, CI95 2.7-5.9) participants and in n = 30 (5%, CI95 3.5
      7.1) applying GOLD spirometric criteria. To analyse risk factors for chronic
      airflow obstruction including those not meeting ATS/ERS or GOLD criteria, FEF25
      75 and FEV1% predicted was analysed in participants without evidence of pulmonary
      restriction among those exposed or not exposed to risk factors (n = 552). FEV1%
      predicted, but in particular FEF25-75 decreased with increasing symptom severity
      of shortness of breath as well as limitations in daily activities of
      participants. Cooking in general and cooking with biomass fuels vs. gas or
      electricity was associated with significantly lower FEF25-75, but not with lower
      FEV1% predicted. Participants having refrained from taking a job because of
      shortness of breath exhibited lower FEF25-75 (p < 0.01). A history of prior
      active TB was the most relevant risk factor associated with a decrease in FEF25
      75 as well as FEV1% predicted. CONCLUSION: This study demonstrated a relevant
      prevalence of chronic airflow obstruction in primary healthcare attendants and
      healthy visitors of a Tanzanian hospital. Using the baseline data provided,
      larger and population-based studies are needed to validate these findings. TB may
      have more impact on development of chronic airway obstruction than smoking in
      Africa. Due to the influence of age on the GOLD definition of chronic airflow
      obstruction, studies should report results using both ATS/ERS and GOLD
      definitions and include age-stratified analysis. Analysis of FEV1 and in
      particular FEF25-75 may yield additional information on risk factors and earlier
      stages of chronic airflow obstruction.

PMID- 29351755
TI  - Bone mineral density at the hip and its relation to fat mass and lean mass in
      adolescents: the Tromso Study, Fit Futures.
AB  - BACKGROUND: Positive association between body weight and bone mass is well
      established, and the concept of body mass index (BMI) is associated with higher
      areal bone mineral density (aBMD) and reduced fracture risk. BMI, that comprises
      both fat mass (FM) and lean mass (LM) may contribute to peak bone mass
      achievement in different ways. This study explored the influence of body
      composition in terms of total body LM and FM on hip aBMD-values in adolescence.
      METHODS: In 2010/2011, 93% of the region's first-year upper-secondary school
      students (15-17 years old) in Tromso, Norway attended the Tromso Study, Fit
      Futures. Areal BMD at femoral neck (aBMDFN) and total hip (aBMDTH) (g/cm2), total
      body LM and FM (g) were measured by dual energy X-ray absorptiometry (DXA).
      Height and weight were measured, and BMI calculated. Lifestyle variables were
      collected by self-administered questionnaires and interviews, including questions
      on time spent on leisure time physical activity. Stratified analyses of
      covariance and regression models included 395 girls and 363 boys. Crude results
      were adjusted for age, height, sexual maturation, physical activity levels,
      vitamin D levels, calcium intake, alcohol consumption and smoking habits.
      RESULTS: Unadjusted distribution indicated higher aBMD-levels at higher LM-levels
      in both genders (p < 0.001), but higher aBMD at higher FM-levels were found only
      in girls (p < 0.018). After multiple adjustments, aBMDFN-levels in girls were
      associated by 0.053 g/cm2 and 0.032 g/cm2 per standard deviation (SD) change in
      LM and FM (p < 0.001). Corresponding values in boys were 0.072 and 0.025 (p <
      0.001). The high LM groups accounted for the highest aBMD-levels, while aBMD
      levels at the LM/FM-combinations indicated different patterns in girls compared
      to boys. The adjusted odds ratio (95% CI) for low levels of aBMDFN was 6.6
      (3.4,13.0) in boys, compared to 2.8 (1.6,4.9) in girls per SD lower LM.
      CONCLUSIONS: LM and FM should be regarded as strong predictors for bone mass and
      hence bone strength in adolescents. A gender specific difference indicated that
      high lean mass is of crucial importance prominently in boys. In adolescents with
      low lean mass, especially in girls, high fat mass may partially ameliorate the
      effect of deficient lean mass levels.

PMID- 29351756
TI  - Disability due to knee pain and somatising tendency in Japanese adults.
AB  - BACKGROUND: Knee pain is common and related to knee osteoarthritis. However,
      there is a discrepancy between knee pain and radiographic osteoarthritis. In the
      general population, knee pain is associated with psychological and cognitive
      factors, which would be one explanation for the discrepancy. Limited evidence
      demonstrates that somatization is associated with knee pain. This study examined
      the association between disability due to knee pain and a high somatising
      tendency. METHODS: Japanese adults (aged 20-64 years) who had experienced knee
      pain in the past four weeks were included in this study (n = 14,695, 50% women).
      Data were extracted from a large internet survey. Somatising tendency was
      assessed using the Somatic Symptom Scale-8 (SSS-8). Disability due to knee pain
      was categorized into three levels: 1) knee pain without difficulty with
      activities of daily living (ADL), 2) knee pain with ADL difficulty but without
      requiring sick leave, and 3) knee pain requiring sick leave. The association
      between >= high somatising tendency (SSS-8 score >= 12) as well as very high
      somatising tendency (SSS-8 score >= 16) and disability due to knee pain was
      examined using logistic regression models adjusted for age, sex, body mass index,
      depressive symptoms, education level, regular exercise, chronicity of knee pain
      (>=3 months), osteoarthritis, rheumatoid arthritis, and fibromyalgia. RESULTS:
      Greater disability due to knee pain was associated with a higher odds ratio for
      >= high somatising tendency (adjusted odds ratio (aOR) = 2.36 [2.10-2.66] in
      group 2 vs. group 1, aOR = 3.23 [2.66-3.92] in group 3 vs. group 1). Stronger
      associations were found for a very high somatising tendency (aOR = 2.80 [2.42
      3.23] in group 2 vs. group 1, aOR = 4.51 [3.64-5.58] in group 3 vs. group 1).
      CONCLUSIONS: Somatization may play a role in disability due to knee pain in the
      general adult population with knee pain, similar to the role of somatization in
      low back pain.

PMID- 29351757
TI  - Major depressive disorder and access to health services among people who use
      illicit drugs in Vancouver, Canada.
AB  - BACKGROUND: People who use illicit drugs (PWUD) are commonly diagnosed with major
      depressive disorder (MDD). However, little is known about whether PWUD living
      with MDD experience additional barriers to accessing health services compared to
      those without MDD. We sought to identify whether MDD symptoms were associated
      with perceived barriers to accessing health services among people who use illicit
      drugs (PWUD) in Vancouver, Canada. METHODS: Data were collected through
      prospective cohorts of PWUD in Vancouver, Canada between 2005 and 2016. Using
      multiple logistic regression, we examined the relationship between MDD symptoms,
      defined as a Centre for Epidemiologic Studies Depression (CES-D) scale total
      score of >=16, and barriers to access health services. We also used descriptive
      statistics to examine common barriers among participants who reported any
      barriers. RESULTS: Among a total of 1529 PWUD, including 521 (34.1%) females, 415
      (27.1%) reported barriers to accessing health services, and 956 (62.5%) reported
      MDD symptoms at baseline. In multiple logistic regression analyses, after
      adjusting for a range of potential confounders, MDD symptoms (adjusted odds ratio
      [AOR] = 1.40; 95% confidence interval [CI]: 1.03-1.92) were positively and
      significantly associated with barriers to accessing health services. Among those
      who reported MDD symptoms and barriers to access, commonly reported barriers
      included: long wait lists/times (38.1%); and treated poorly by health care
      professionals (30.0%). CONCLUSION: These findings show that the likelihood of
      experiencing barriers to accessing health services was higher among PWUD with MDD
      symptoms compared to their counterparts. Policies and interventions tailored to
      address these barriers are urgently needed for this subpopulation of PWUD.

PMID- 29351758
TI  - Autophagy promotes metastasis and glycolysis by upregulating MCT1 expression and
      Wnt/beta-catenin signaling pathway activation in hepatocellular carcinoma cells.
AB  - BACKGROUND: Autophagy is a dynamic physiological process that can generate energy
      and nutrients for cell survival during stress. Autophagy can regulate the
      migration and invasive ability in cancer cells. However, the connection between
      autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays
      an important role in lactic acid transport and H+ clearance in cancer cells, and
      Wnt/beta-catenin signaling can increase cancer cell glycolysis. We investigated
      whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by
      activating the Wnt/beta-catenin signaling pathway, accompanied by MCT1
      upregulation. METHODS: Autophagic activity was evaluated using western blotting,
      immunoblotting, and transmission electron microscopy. The underlying mechanisms
      of autophagy activation on HCC cell glycolysis were studied via western blotting,
      and Transwell, lactate, and glucose assays. MCT1 expression was detected using
      quantitative reverse transcription-PCR (real-time PCR), western blotting, and
      immunostaining of HCC tissues and the paired adjacent tissues. RESULTS: Autophagy
      promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/beta-catenin
      signaling pathway activation mediated the effect of autophagy on HCC cell
      glycolysis. beta-Catenin downregulation inhibited the autophagy-induced
      glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was
      highly expressed in HCC tissues, and high MCT1 expression correlated positively
      with the expression of microtubule-associated protein light chain 3 (LC3).
      CONCLUSION: Activation of autophagy can promote metastasis and glycolysis in HCC
      cells, and autophagy induces MCT1 expression by activating Wnt/beta-catenin
      signaling. Our study describes the connection between autophagy and glucose
      metabolism in HCC cells and may provide a potential therapeutic target for HCC
      treatment.

PMID- 29351759
TI  - Tracheal intubation in critically ill patients: a comprehensive systematic review
      of randomized trials.
AB  - BACKGROUND: We performed a systematic review of randomized controlled studies
      evaluating any drug, technique or device aimed at improving the success rate or
      safety of tracheal intubation in the critically ill. METHODS: We searched PubMed,
      BioMed Central, Embase and the Cochrane Central Register of Clinical Trials and
      references of retrieved articles. Finally, pertinent reviews were also scanned to
      detect further studies until May 2017. The following inclusion criteria were
      considered: tracheal intubation in adult critically ill patients; randomized
      controlled trial; study performed in Intensive Care Unit, Emergency Department or
      ordinary ward; and work published in the last 20 years. Exclusion criteria were
      pre-hospital or operating theatre settings and simulation-based studies. Two
      investigators selected studies for the final analysis. Extracted data included
      first author, publication year, characteristics of patients and clinical
      settings, intervention details, comparators and relevant outcomes. The risk of
      bias was assessed with the Cochrane Collaboration's Risk of Bias tool. RESULTS:
      We identified 22 trials on use of a pre-procedure check-list (1 study), pre
      oxygenation or apneic oxygenation (6 studies), sedatives (3 studies),
      neuromuscular blocking agents (1 study), patient positioning (1 study), video
      laryngoscopy (9 studies), and post-intubation lung recruitment (1 study). Pre
      oxygenation with non-invasive ventilation (NIV) and/or high-flow nasal cannula
      (HFNC) showed a possible beneficial role. Post-intubation recruitment improved
      oxygenation, while ramped position increased the number of intubation attempts
      and thiopental had negative hemodynamic effects. No effect was found for use of a
      checklist, apneic oxygenation (on oxygenation and hemodynamics),
      videolaryngoscopy (on number and length of intubation attempts), sedatives and
      neuromuscular blockers (on hemodynamics). Finally, videolaryngoscopy was
      associated with severe adverse effects in multiple trials. CONCLUSIONS: The
      limited available evidence supports a beneficial role of pre-oxygenation with NIV
      and HFNC before intubation of critically ill patients. Recruitment maneuvers may
      increase post-intubation oxygenation. Ramped position increased the number of
      intubation attempts; thiopental had negative hemodynamic effects and
      videolaryngoscopy might favor adverse events.

PMID- 29351760
TI  - Glycaemic control targets after traumatic brain injury: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Optimal glycaemic targets in traumatic brain injury (TBI) remain
      unclear. We performed a systematic review and meta-analysis of randomised
      controlled trials (RCTs) comparing intensive with conventional glycaemic control
      in TBI requiring admission to an intensive care unit (ICU). METHODS: We
      systematically searched MEDLINE, EMBASE and the Cochrane Central Register of
      Controlled Trials to November 2016. Outcomes of interest included ICU and in
      hospital mortality, poor neurological outcome, the incidence of hypoglycaemia and
      infective complications. Data were analysed by pairwise random effects models
      with secondary analysis of differing levels of conventional glycaemic control.
      RESULTS: Ten RCTs, involving 1066 TBI patients were included. Three studies were
      conducted exclusively in a TBI population, whereas in seven trials, the TBI
      population was a sub-cohort of a mixed neurocritical or general ICU population.
      Glycaemic targets with intensive control ranged from 4.4 to 6.7 mmol/L, while
      conventional targets aimed to keep glucose levels below thresholds of 8.4-12
      mmol/L. Conventional versus intensive control showed no association with ICU or
      hospital mortality (relative risk (RR) (95% CI) 0.93 (0.68-1.27), P = 0.64 and
      1.07 (0.84-1.36), P = 0.62, respectively). The risk of a poor neurological
      outcome was higher with conventional control (RR (95% CI) = 1.10 (1.001-1.24), P
      = 0.047). However, severe hypoglycaemia occurred less frequently with
      conventional control (RR (95% CI) = 0.22 (0.09-0.52), P = 0.001). CONCLUSIONS:
      This meta-analysis of intensive glycaemic control shows no association with
      reduced mortality in TBI. Intensive glucose control showed a borderline
      significant reduction in the risk of poor neurological outcome, but markedly
      increased the risk of hypoglycaemia. These contradictory findings should motivate
      further research.

PMID- 29351762
TI  - Inclusion of edaphic predictors for enhancement of models to determine
      distribution of soil-transmitted helminths: the case of Zimbabwe.
AB  - BACKGROUND: Reliable mapping of soil-transmitted helminth (STH) parasites
      requires rigorous statistical and machine learning algorithms capable of
      integrating the combined influence of several determinants to predict
      distributions. This study tested whether combining edaphic predictors with
      relevant environmental predictors improves model performance when predicting the
      distribution of STH, Ascaris lumbricoides and hookworms at a national scale in
      Zimbabwe. METHODS: Geo-referenced parasitological data obtained from a 2010/2011
      national survey indicating a confirmed presence or absence of STH among school
      children aged 10-15 years was used to calibrate ten species distribution models
      (SDMs). The performance of SDMs calibrated with a set of environmental and
      edaphic variables was compared to that of SDMs calibrated with environmental
      variables only. Model performance was evaluated using the true skill statistic
      and receiver operating characteristic curve. RESULTS: Results show a significant
      improvement in model performance for both A. lumbricoides and hookworms for all
      ten SDMs after edaphic variables were combined with environmental variables in
      the modelling of the geographical distribution of the two STHs at national scale.
      Using the top three performing models, a consensus prediction was developed to
      generate the first continuous maps of the potential distribution of the two STHs
      in Zimbabwe. CONCLUSIONS: The findings from this study demonstrate significant
      model improvement if relevant edaphic variables are included in model calibration
      resulting in more accurate mapping of STH. The results also provide spatially
      explicit information to aid targeted control of STHs in Zimbabwe and other
      countries with STH burden.

PMID- 29351761
TI  - Selective serotonin reuptake inhibitor use and breast cancer survival: a
      population-based cohort study.
AB  - BACKGROUND: Nearly 50% of breast cancer patients suffer from depression or
      anxiety. Selective serotonin reuptake inhibitors (SSRIs), the first-line
      pharmacological treatment for depression, have been implicated in breast cancer
      development through increased prolactin levels and tamoxifen metabolism
      inhibition. Previous studies of breast cancer progression have focused on
      tamoxifen users, or have been limited by their small sample size and methodology.
      Therefore, we used UK population-based data to more robustly investigate the
      association between SSRI use and cancer-specific mortality. METHODS: A cohort of
      patients with newly-diagnosed breast cancer between 1998 and 2012 was selected
      from English cancer registries and linked to prescription records from the
      Clinical Practice Research Datalink, and to death records from the Office for
      National Statistics. We used Cox regression models to calculate hazard ratios
      (HRs) comparing mortality between post-diagnostic SSRI users and non-users (using
      time-dependant covariates), after adjusting for demographics, comorbidities and
      pre-diagnosis use of hormone replacement therapy or oral contraceptives. We
      conducted several additional analyses to assess causality. RESULTS: Our cohort
      included 23,669 breast cancer patients, of which 2672 used SSRIs and 3053 died
      due to their breast cancer during follow-up. After adjustment, SSRI users had
      higher breast cancer-specific mortality than non-users (HR = 1.27; 95% confidence
      interval (CI) 1.16, 1.40). However, this association was attenuated when
      restricting to patients with a prior history of depression (HR = 1.14; 95% CI
      0.98, 1.33), and when comparing to users of other antidepressant medications (HR
      = 1.06; 95% CI 0.93, 1.20). There was some evidence of higher mortality among
      long-term SSRI users, even when restricting to patients with prior depression (HR
      = 1.54; 95% CI 1.03, 2.29). CONCLUSIONS: In this large breast cancer cohort, SSRI
      use was associated with a 27% increase in breast cancer mortality. The cause of
      this is unknown; however, confounding by indication seems likely as it was
      largely attenuated when restricting to patients with prior depression, or when
      comparing SSRIs to other antidepressant medications. Clinicians should not be
      unduly concerned when prescribing SSRIs to breast cancer patients, but the
      increase in mortality among long-term SSRI users warrants further investigation.

PMID- 29351763
TI  - An overview of the impact of rare disease characteristics on research
      methodology.
AB  - BACKGROUND: About 30 million individuals in the United States are living with a
      rare disease, which by definition have a prevalence of 200,000 or fewer cases in
      the United States ([National Organization for Rare Disorders], [About NORD],
      [2016]). Disease heterogeneity and geographic dispersion add to the difficulty of
      completing robust studies in small populations. Improving the ability to conduct
      research on rare diseases would have a significant impact on population health.
      The purpose of this paper is to raise awareness of methodological approaches that
      can address the challenges to conducting robust research on rare diseases.
      APPROACH: We conducted a landscape review of available methodological and
      analytic approaches to address the challenges of rare disease research. Our
      objectives were to: 1. identify algorithms for matching study design to rare
      disease attributes and the methodological approaches applicable to these
      algorithms; 2. draw inferences on how research communities and infrastructure can
      contribute to the efficiency of research on rare diseases; and 3. to describe
      methodological approaches in the rare disease portfolio of the Patient-Centered
      Outcomes Research Institute (PCORI), a funder promoting both rare disease
      research and research infrastructure. RESULTS: We identified three algorithms for
      matching study design to rare disease or intervention characteristics (Gagne,
      et.al, BMJ 349:g6802, 2014); (Gupta, et.al, J Clin Epidemiol 64:1085-1094, 2011);
      (Cornu, et. al, Orphet J Rare Dis 8:48,2012) and summarized the applicable
      methodological and analytic approaches. From this literature we were also able to
      draw inferences on how an effective research infrastructure can set an agenda,
      prioritize studies, accelerate accrual, catalyze patient engagement and terminate
      poorly performing studies. Of the 24 rare disease projects in the PCORI
      portfolio, 11 are randomized controlled trials (RCTs) using standard designs.
      Thirteen are observational studies using case-control, prospective cohort, or
      natural history designs. PCORI has supported the development of 9 Patient-Powered
      Research Networks (PPRNs) focused on rare diseases. CONCLUSION: Matching research
      design to attributes of rare diseases and interventions can facilitate the
      completion of RCTs that are adequately powered. An effective research
      infrastructure can improve efficiency and avoid waste in rare disease research.
      Our review of the PCORI research portfolio demonstrates that it is feasible to
      conduct RCTs in rare disease. However, most of these studies are using standard
      RCT designs. This suggests that use of a broader array of methodological
      approaches to RCTs --such as adaptive trials, cross-over trials, and early escape
      designs can improve the productivity of robust research in rare diseases.

PMID- 29351764
TI  - Quantification and kinetics of viral RNA transcripts produced in Orthohantavirus
      infected cells.
AB  - BACKGROUND: Rodent borne viruses of the Orthohantavirus genus cause hemorrhagic
      fever with renal syndrome among people in Eurasia, and hantavirus cardiopulmonary
      syndrome in the Americas. At present, there are no specific treatments or
      efficient vaccines against these diseases. Improved understanding of viral
      transcription and replication may instigate targeted treatment of Orthohantavirus
      infections. For this purpose, we investigated the kinetics and levels of viral
      RNA transcription during an ongoing infection in-vitro. METHODS: Vero E6 cells
      were infected with Puumala Orthohantavirus (strain Kazan) before cells and
      supernatants were collected at different time points post infection for the
      detection of viral RNAs. A plasmid containing primer binding sites of the three
      Orthohantavirus segments small (S), medium (M) and large (L) was constructed and
      standard curves were generated to calculate the copy numbers of the individual
      transcripts in the collected samples. RESULTS: Our results indicated a rapid
      increase in the copy number of viral RNAs after 9 h post infection. At peak days,
      2-6 days after infection, the S- and M-segment transcripts became thousand and
      hundred-fold more abundant than the copy number of the L-segment RNA,
      respectively. The presence of viral RNA in the cell culture media was detected at
      later time-points. CONCLUSIONS: We have developed a method to follow RNA
      transcription in-vitro after synchronous infection of Vero cells. The obtained
      results may contribute to the understanding of the viral replication, and may
      have implications in the development of antiviral drugs targeting transcription
      or replication of negative stranded RNA viruses.

PMID- 29351765
TI  - Retrospective analysis of insulin responses to standard dosed oral glucose tests
      (OGTs) via naso-gastric tubing towards definition of an objective cut-off value.
AB  - BACKGROUND: Insulin dysregulation (ID) with basal or postprandial
      hyperinsulinemia is one of the key findings in horses and ponies suffering from
      the equine metabolic syndrome (EMS). Assessment of ID can easily be performed in
      clinical settings by the use of oral glucose challenge tests. Oral glucose test
      (OGT) performed with 1 g/kg bodyweight (BW) glucose administered via naso-gastric
      tube allows the exact administration of a defined glucose dosage in a short time.
      However, reliable cut-off values have not been available so far. Therefore, the
      aim of the study was to describe variations in insulin response to OGT via naso
      gastric tubing and to provide a clinical useful cut-off value for ID when using
      the insulin quantification performed with an equine-optimized insulin enzyme
      linked immunosorbent assay. RESULTS: Data visualization revealed no clear
      separation in the serum insulin concentration of insulin sensitive and insulin
      dysregulated horses during OGT. Therefore, a model based clustering method was
      used to circumvent the use of an arbitrary limit for categorization. This method
      considered all data-points for the classification, taking into account the
      individual insulin trajectory during the OGT. With this method two clusters were
      differentiated, one with low and one with high insulin responses during OGT. The
      cluster of individuals with low insulin response was consistently detected,
      independently of the initialization parameters of the algorithm. In this cluster
      the 97.5% quantile of insulin is 110 uLU/mL at 120 min. We suggest using this
      insulin concentration of 110 uLU/mL as a cut-off value for samples obtained at
      120 min in OGT. CONCLUSION: OGT performed with 1 g/kg BW glucose and
      administration via naso-gastric tubing can easily be performed under clinical
      settings. Application of the cut-off value of 110 uLU/mL at 120 min allows
      assessment of ID in horses.

PMID- 29351766
TI  - Efficacy and safety of Sofosbuvir-containing regimens in patients co-infected
      with chronic hepatitis C virus and human immunodeficiency virus: a meta-analysis.
AB  - BACKGROUND: The treatment of hepatitis C virus (HCV) in HCV/human
      immunodeficiency virus (HIV) co-infected patients remains complex. This present
      meta-analysis evaluated the efficacy and safety of Sofosbuvir (SOF) for treatment
      in HCV/HIV co-infected patients using the most recent and available data.
      METHODS: A systematic search of the published data was conducted in PubMed
      Medline, EMBASE and Cochrane databases. Eligible studies were clinical trials,
      case-control studies or prospective cohort studies aiming at assessing the
      efficacy and safety of the SOF-containing regimens in patients co-infected with
      HCV and HIV. Heterogeneity of results was assessed and a pooled analysis was
      performed using random effects model with maximum likelihood estimate and 95%
      confidence intervals (95%CI). Subgroup analysis and assessment of publication
      bias through Egger's test were also performed. STATA 13.0 software was used to
      analyze the data. RESULTS: Seven studies (n = 1167 co-infected patients) were
      included in this analysis. The pooled estimate of sustained virological response
      at 12 weeks (SVR12) was 94.0% (95%CI: 92.0%-95.0%). Subgroup analysis showed that
      the treatment-naive patients had higher SVR12 compared with patients that were
      treated before (chi2 = 21.39, P < 0.01). The pooled incidence of any adverse
      events (AEs) was 79.6% (95%CI: 77.1%-82.1%). Publication bias did not exist.
      CONCLUSION: The results of this study showed that the treatment response of SOF
      containing regimens in patients co-infected with HIV and HCV was satisfied.
      Attention should be paid to the high rates of AEs.

PMID- 29351767
TI  - Leading for the long haul: a mixed-method evaluation of the Sustainment
      Leadership Scale (SLS).
AB  - BACKGROUND: Despite our progress in understanding the organizational context for
      implementation and specifically the role of leadership in implementation, its
      role in sustainment has received little attention. This paper took a mixed-method
      approach to examine leadership during the sustainment phase of the Exploration,
      Preparation, Implementation, Sustainment (EPIS) framework. Utilizing the
      Implementation Leadership Scale as a foundation, we sought to develop a short,
      practical measure of sustainment leadership that can be used for both applied and
      research purposes. METHODS: Data for this study were collected as a part of a
      larger mixed-method study of evidence-based intervention, SafeCare(r),
      sustainment. Quantitative data were collected from 157 providers using web-based
      surveys. Confirmatory factor analysis was used to examine the factor structure of
      the Sustainment Leadership Scale (SLS). Qualitative data were collected from 95
      providers who participated in one of 15 focus groups. A framework approach guided
      qualitative data analysis. Mixed-method integration was also utilized to examine
      convergence of quantitative and qualitative findings. RESULTS: Confirmatory
      factor analysis supported the a priori higher order factor structure of the SLS
      with subscales indicating a single higher order sustainment leadership factor.
      The SLS demonstrated excellent internal consistency reliability. Qualitative
      analyses offered support for the dimensions of sustainment leadership captured by
      the quantitative measure, in addition to uncovering a fifth possible factor,
      available leadership. CONCLUSIONS: This study found qualitative and quantitative
      support for the pragmatic SLS measure. The SLS can be used for assessing
      leadership of first-level leaders to understand how staff perceive leadership
      during sustainment and to suggest areas where leaders could direct more attention
      in order to increase the likelihood that EBIs are institutionalized into the
      normal functioning of the organization.

PMID- 29351768
TI  - Overweight in adult cats: a cross-sectional study.
AB  - BACKGROUND: Overweight in cats is a major risk factor for diabetes mellitus and
      has also been associated with other disorders. Overweight and obesity are
      believed to be increasing problems in cats, as is currently seen in people, with
      important health consequences. The objectives of the present study were to
      determine the prevalence of overweight in cats from two different cohorts in a
      cross-sectional study design and to assess associations between overweight and
      diagnoses, and between overweight and demographic and environmental factors. Data
      were obtained from medical records for cats (n = 1072) visiting an academic
      medical center during 2013-2015, and from a questionnaire on insured cats (n =
      1665). From the medical records, information on body condition score, breed, age,
      sex, neutering status, and diagnosis was obtained. The questionnaire included
      questions relating to the cat's body condition, breed, age, sex, neutering
      status, outdoor access, activity level, and diet. Data were analyzed by
      multivariable logistic regression. RESULTS: The prevalence of overweight was 45%
      in the medical records cohort and 22% in the questionnaire cohort, where owners
      judged their pet's body condition. Overweight cats in the medical records cohort
      were more likely to be diagnosed with lower urinary tract disease, diabetes
      mellitus, respiratory disease, skin disorders, locomotor disease, and trauma.
      Eating predominantly dry food, being a greedy eater, and inactivity were factors
      associated with an increased risk of overweight in the final model in the
      questionnaire cohort. In both cohorts, the Birman and Persian breeds, and
      geriatric cats, were less likely to be overweight, and male cats were more likely
      to be overweight. CONCLUSIONS: The prevalence of overweight cats (45%) as
      assessed by trained personnel was high and in the same range as previously
      reported. Birman and Persian cats had a lower risk of overweight. The association
      with dry food found in adult, neutered cats is potentially important because this
      type of food is commonly fed to cats worldwide, and warrants further attention.
      Drawbacks related to the study design need to be acknowledged when interpreting
      the results, such as a potential for selection bias for cats visiting an animal
      hospital, and an information bias for questionnaire data. The high occurrence of
      overweight in cats needs to be addressed because it negatively affects their
      health.

PMID- 29351770
TI  - "I struggle to count my blessings": recovery after hip fracture from the
      patients' perspective.
AB  - BACKGROUND: Recovery outlooks of physical functioning and quality of life after
      hip fracture have not changed significantly over the past 25 years. Previous
      research has mainly dealt with causalities and acute treatment, while the
      recovery process from the patients' perspective has been less comprehensively
      described. Expanded knowledge of what the patients consider important in their
      recovery process may have important consequences for how these patients are
      treated in the future and thereby on future patient outcomes. The aim presently
      is therefore to explore how elderly patients with hip fracture enrolled in an
      ongoing RCT have experienced their recovery process. METHOD: The study was
      qualitative in design. Eight frail elderly in recovery after hip fracture (aged
      69-91) were interviewed in their home four months after their fracture. The
      interviews covered issues related to their experiences of facilitators and
      barriers throughout the different stages in the recovery process. The patients
      were already enrolled in an ongoing randomized controlled trial, examining the
      effects of habitual functional training during their short term stays at nursing
      homes. The patients were chosen strategically according to age, gender, and
      participation in rehabilitation. The interviews were recorded, transcribed and
      subjected to a method of systematic text condensation inspired by Giorgi's
      phenomenological method. RESULTS: The results revealed that the patients'
      experiences of the recovery process fell into three main themes: "Feeling
      vulnerable", "A span between self-reliance and dependency" and "Disruption from a
      normal life". The feeling of gloominess and vulnerability persisted throughout.
      Being in recovery was also experienced as a tension between self-reliance and
      dependency; a disrupted life where loss of mobility and the impact of age was
      profoundly present. CONCLUSION: Being in recovery after hip fracture was
      experienced as a life breaking event. Based on these findings, increased focus on
      individualized treatment to each patient through each stage of the recovery
      process should be emphasized.

PMID- 29351769
TI  - Protocol to disseminate a hospital-site controlled intervention using audit and
      feedback to implement guidelines concerning inappropriate treatment of
      asymptomatic bacteriuria.
AB  - BACKGROUND: Antimicrobial stewardship to combat the spread of antibiotic
      resistant bacteria has become a national priority. This project focuses on
      reducing inappropriate use of antimicrobials for asymptomatic bacteriuria (ASB),
      a very common condition that leads to antimicrobial overuse in acute and long
      term care. We previously conducted a successful intervention, entitled "Kicking
      Catheter Associated Urinary Tract Infection (CAUTI): the No Knee-Jerk Antibiotics
      Campaign," to decrease guideline-discordant ordering of urine cultures and
      antibiotics for ASB. The current objective is to facilitate implementation of a
      scalable version of the Kicking CAUTI campaign across four geographically diverse
      Veterans Health Administration facilities while assessing what aspects of an
      antimicrobial stewardship intervention are essential to success and
      sustainability. METHODS: This project uses an interrupted time series design with
      four control sites. The two main intervention tools are (1) an evidence-based
      algorithm that distills the guidelines into a streamlined clinical pathway and
      (2) case-based audit and feedback to train clinicians to use the algorithm. Our
      conceptual framework for the development and implementation of this intervention
      draws on May's General Theory of Implementation. The intervention is directed at
      providers in acute and long-term care, and the goal is to reduce inappropriate
      screening for and treatment of ASB in all patients and residents, not just those
      with urinary catheters. The start-up for each facility consists of centrally-led
      phone calls with local site champions and baseline surveys. Case-based audit and
      feedback will begin at a given site after the start-up period and continue for 12
      months, followed by a sustainability assessment. In addition to the clinical
      outcomes, we will explore the relationship between the dose of the intervention
      and clinical outcomes. DISCUSSION: This project moves from a proof-of-concept
      effectiveness study to implementation involving significantly more sites, and
      uses the General Theory of Implementation to embed the intervention into normal
      processes of care with usual care providers. Aspects of implementation that will
      be explored include dissemination, internal and external facilitation, and
      organizational partnerships. "Less is More" is the natural next step from our
      prior successful Kicking CAUTI intervention, and has the potential to improve
      patient care while advancing the science of implementation.

PMID- 29351771
TI  - Characterization of Salmonella enterica from invasive bloodstream infections and
      water sources in rural Ghana.
AB  - BACKGROUND: Non-typhoidal Salmonella (NTS) cause the majority of bloodstream
      infections in Ghana, however the mode of transmission and source of invasive NTS
      in Africa are poorly understood. This study compares NTS from water sources and
      invasive bloodstream infections in rural Ghana. METHODS: Blood from hospitalised,
      febrile children and samples from drinking water sources were analysed for
      Salmonella spp. Strains were serotyped to trace possible epidemiological links
      between human and water-derived isolates.. Antibiotic susceptibility testing was
      performed, RESULTS: In 2720 blood culture samples, 165 (6%) NTS were isolated. S.
      Typhimurium (70%) was the most common serovar followed by S. Enteritidis (8%) and
      S. Dublin (8%). Multidrug resistance (MDR) was found in 95 (58%) NTS isolates,
      including five S. Enteritidis. One S. Typhimurium showed reduced fluroquinolone
      susceptibility. In 511 water samples, 19 (4%) tested positive for S. enterica
      with two isolates being resistant to ampicillin and one isolate being resistant
      to cotrimoxazole. Serovars from water samples were not encountered in any of the
      clinical specimens. CONCLUSION: Water analyses demonstrated that common drinking
      water sources were contaminated with S. enterica posing a potential risk for
      transmission. However, a link between S. enterica from water sources and patients
      could not be established, questioning the ability of water-derived serovars to
      cause invasive bloodstream infections.

PMID- 29351772
TI  - Effect of an interactive E-learning tool for delirium on patient and nursing
      outcomes in a geriatric hospital setting: findings of a before-after study.
AB  - BACKGROUND: Education of healthcare workers is a core element of multicomponent
      delirium strategies to improve delirium care and, consequently, patient outcomes.
      However, traditional educational strategies are notoriously difficult to
      implement. E-learning is hypothesised to be easier and more cost effective, but
      research evaluating effectiveness of delirium education through e-learning is
      scarce at present. Aim is to determine the effect of a nursing e-learning tool
      for delirium on: (1) in-hospital prevalence, duration and severity of delirium or
      mortality in hospitalized geriatric patients, and (2) geriatric nurses' knowledge
      and recognition regarding delirium. METHODS: A before-after study in a sample of
      patients enrolled pre-intervention (non-intervention cohort (NIC); n = 81) and
      post-intervention (intervention cohort (IC); n = 79), and nurses (n = 17) of a
      geriatric ward (university hospital). The intervention included an information
      session about using the e-learning tool, which consisted of 11 e-modules
      incorporating development of knowledge and skills in the prevention, detection
      and management of delirium, and the completion of a delirium e-learning tool
      during a three-month period. Key patient outcomes included in-hospital prevalence
      and duration of delirium (Confusion Assessment Method), delirium severity
      (Delirium Index) and mortality (in-hospital; 12 months post-admission); key nurse
      outcomes included delirium knowledge (Delirium Knowledge Questionnaire) and
      recognition (Case vignettes). Logistic regression and linear mixed models were
      used to analyse patient data; Wilcoxon Signed Rank tests, McNemar's or paired t
      tests for nursing data. RESULTS: No significant difference was found between the
      IC and NIC for in-hospital prevalence (21.5% versus 25.9%; p = 0.51) and duration
      of delirium (mean 4.2 +/- SD 4.8 days versus 4.9 +/- SD 4.8 days; p = 0.38). A
      trend towards a statistically significant lower delirium severity (IC versus NIC:
      difference estimate - 1.59; p = 0.08) was noted for delirious IC patients in a
      linear mixed model. No effect on patient mortality and on nurses' delirium
      knowledge (p = 0.43) and recognition (p = 1.0) was found. CONCLUSION: Our study,
      the first in its area to investigate effects of delirium e-learning on patient
      outcomes, demonstrated no benefits on both geriatric patients and nurses. Further
      research is needed to determine whether delirium e-learning nested within a
      larger educational approach inclusive of enabling and reinforcing strategies,
      would be effective. TRIAL REGISTRATION: ISRCTN ( 82,293,702 , 27/06/2017).

PMID- 29351773
TI  - Treatment of long-segment Barrett's adenocarcinoma by complete circular
      endoscopic submucosal dissection: a case report.
AB  - BACKGROUND: We present the first description of en bloc endoscopic submucosal
      dissection (ESD) for total circumferential Barrett's adenocarcinoma,
      predominantly of the long-segment Barrett's esophagus (LSBE), with a 2-year
      follow-up and management strategies for esophageal stricture prevention. CASE
      PRESENTATION: A 59-year-old man was diagnosed with LSBE and Barrett's
      adenocarcinoma by esophagogastroduodenoscopy (EGD). A 55-mm-long circumferential
      tumor was completely resected by ESD. Histopathology revealed a well
      differentiated adenocarcinoma within the LSBE superficial muscularis mucosa. For
      post-ESD stricture prevention, the patient underwent an endoscopic triamcinolone
      injection administration, oral prednisolone administration, and preemptive
      endoscopic balloon dilatation. Two years later, there is no evidence of
      esophageal stricture or recurrence. CONCLUSIONS: ESD appears to be a safe,
      effective option for total circumferential Barrett's adenocarcinoma in LSBE.

PMID- 29351774
TI  - Inflammatory bowel disease (IBD) in horses: a retrospective study exploring the
      value of different diagnostic approaches.
AB  - BACKGROUND: Diagnosing IBD in horses is challenging and requires a multimodal
      approach, since no conclusive diagnostic test is available. The objectives of
      this study were to provide an overview of population characteristics, results of
      applied diagnostic tests, treatment modalities and outcome in a large group of
      horses thought to have IBD and that were presented to four large equine referral
      hospitals, and to provide an exploratory investigation of possible associations
      between results of applied diagnostic tests, applied treatment modalities and
      outcome. A retrospective case series was performed across four large equine
      referral hospitals. Seventy-eight horses, thought to have IBD were included. Case
      history, clinical findings, diagnostic test results including oral glucose
      tolerance test (OGTT) and enteral biopsies (both duodenal and rectal), applied
      therapy and outcome were studied. A Chi-Square test was used to identify
      associations between results of diagnostic tests, treatment and outcome. P-values
      < 0.05 were considered significant. RESULTS: Lethargy, diarrhoea, recurrent colic
      and weight loss were recorded in respectively 21,8%; 14,1%; 28,2% and 78,2% of
      cases. Over 70% of horses thought to have IBD had an abnormal OGTT. Only weight
      loss was significantly associated with aberrant enteral biopsy results, but not
      with abnormal OGTT results or low blood total protein. There was no association
      between an aberrant biopsy result and a disturbed OGTT. There was no association
      between either OGTT results or enteral biopsy results and a low blood total
      protein content, presence of gastric ulcer disease or an aberrant endoscopic
      aspect of the duodenal entrance. CONCLUSIONS: Weight loss is a highly prevalent
      symptom in IBD suspected horses. Enteral biopsies may be a useful diagnostic aid
      in the work-up of horses thought to suffer from IBD, however further research is
      required to demonstrate their true diagnostic value. Until more standardized
      scientific research is available, one should be careful with the interpretation
      of enteral biopsy results There is a need for better standardization of enteral
      biopsy procedures and the histopathological scoring of biopsies.

PMID- 29351775
TI  - Vaccine resistant pseudorabies virus causes mink infection in China.
AB  - BACKGROUND: Pseudorabies, a highly contagious infectious disease of swine is
      caused by pseudorabies virus (PRV). PRV can cause fatal infection in other animal
      species. RESULTS: We report a deadly outbreak of pseudorabies that killed 87.2%
      (3522/4028) minks in a farm in 2014 in Shandong Province, China. PRV was isolated
      by using Vero cell culture and detected in mink samples by PCR from minks died
      during the outbreak. Epidemiological analysis indicated that 5.8% of minks
      (33/566) were PCR positive to PRV in Shandong Province. Phylogenetic analysis
      indicated that the PRV strains isolated from minks in this study were in the same
      clade with the Chinese porcine PRV isolates, which are resistant to the PRV
      vaccine. CONCLUSIONS: We demonstrated that pseudorabies virus caused an outbreak
      of minks in a farm in Shandong Province of China and the virus has a very high
      infection rate in minks in Shandong Province, which is a challenge for the fur
      industry in China.

PMID- 29351776
TI  - Readmission rates in not-for-profit vs. proprietary hospitals before and after
      the hospital readmission reduction program implementation.
AB  - BACKGROUND: The Patient Protection and Affordable Care Act established the
      Hospital Readmission Reduction Program (HRRP) to penalize hospitals with
      excessive 30-day hospital readmissions of Medicare enrollees for specific
      conditions. This policy was aimed at increasing the quality of care delivered to
      patients and decreasing the amount of money paid for potentially preventable
      hospital readmissions. While it has been established that the number of 30-day
      hospital readmissions decreased after program implementation, it is unknown
      whether this effect occurred equally between not-for-profit and proprietary
      hospitals. The aim of this study was to determine whether or not the HRRP
      decreased readmission rates equally between not-for-profit and proprietary
      hospitals between 2010 and 2012. METHODS: Data on readmissions came from the
      Dartmouth Atlas and hospital ownership data came from the Centers for Medicare
      and Medicaid Services. Data were joined using the Medicare provider number. Using
      a difference-in-differences approach, bivariate and regression analyses were
      conducted to compare readmission rates between not-for-profit and proprietary
      hospitals between 2010 and 2012 and were adjusted for hospital characteristics.
      RESULTS: In 2010, prior to program implementation, unadjusted readmission rates
      for proprietary and not-for-profit hospitals were 16.16% and 15.78%,
      respectively. In 2012, following program implementation, 30-day readmission rates
      dropped to 15.76% and 15.29% for proprietary and not-for-profit hospitals. The
      data suggest that the implementation of the Hospital Readmission Reduction
      Program had similar effects on not-for-profit and proprietary hospitals with
      respect to readmission rates, even after adjusting for confounders. CONCLUSIONS:
      Although not-for-profit hospitals had lower 30-day readmission rates than
      proprietary hospitals in both 2010 and 2012, they both decreased after the
      implementation of the HRRP and the decreases were not statistically significantly
      different. Thus, this study suggests that the Hospital Readmission Reduction
      Program was equally effective in reducing readmission rates, despite ownership
      status.

PMID- 29351777
TI  - Are minor alleles more likely to be risk alleles?
AB  - BACKGROUND: Genome-wide association studies (GWASs) have revealed relationships
      between over 57,000 genetic variants and diseases. However, unlike Mendelian
      diseases, complex diseases arise from the interplay of multiple genetic and
      environmental factors. Natural selection has led to a high tendency of risk
      alleles to be enriched in minor alleles in Mendelian diseases. Therefore, an
      allele that was previously advantageous or neutral may later become harmful,
      making it a risk allele. METHODS: Using data in the NHGRI-EBI Catalog and the
      VARIMED database, we investigated whether (1) GWASs more easily detect risk
      alleles and (2) facilitate evolutionary insights by comparing risk allele
      frequencies of different diseases. We conducted computer simulations of P-values
      for association tests when major and minor alleles were risk alleles. We compared
      the expected proportion of SNVs whose risk alleles were minor alleles with the
      observed proportion. RESULTS: Our statistical results revealed that risk alleles
      were enriched in minor alleles, especially for variants with low minor allele
      frequencies (MAFs < 0.1). Our computer simulations revealed that > 50% risk
      alleles were minor alleles because of the larger difference in the power of GWASs
      to differentiate between minor and major alleles, especially with low MAFs or
      when the number of controls exceeds the number of cases. However, the observed
      ratios between minor and major alleles in low MAFs (< 0.1) were much larger than
      the expected ratios of GWAS's power imbalance, especially for diseases whose
      average risk allele frequencies were low, such as myopia, sudden cardiac arrest,
      and systemic lupus erythematosus. CONCLUSIONS: Minor alleles are more likely to
      be risk alleles in the published GWASs on complex diseases. One reason is that
      minor alleles are more easily detected as risk alleles in GWASs. Even when
      correcting for the GWAS's power imbalance, minor alleles are more likely to be
      risk alleles, especially in some diseases whose average risk allele frequencies
      are low. These analyses serve as a starting point for future studies on
      quantifying the degree of negative natural selection in various complex diseases.

PMID- 29351778
TI  - A qualitative analysis of men's involvement in maternal and child health as a
      policy intervention in rural Central Malawi.
AB  - BACKGROUND: Men's involvement in maternal and child health presents an
      opportunity for the advancement of maternal and child nutrition as men often play
      a key role in decision-making particularly regarding women's reproductive health.
      While most research on men's involvement in maternal and child health has focused
      on men's participation in antenatal care, this study focuses specifically on
      men's involvement in maternal and child nutrition. The purpose of the study is to
      explore how men's involvement is conceptualised in rural Central Malawi,
      highlighting the key factors influencing men's involvement in maternal and child
      health. METHODS: Focus group discussions and in-depth interviews were conducted
      with 26 informants and 44 community members. Critical policy was used as the
      theoretical framework to inform the analysis of research findings. RESULTS: In
      this study, we identified several factors that facilitate men's involvement in
      maternal and child health, but we also identified several barriers. Facilitators
      of men's involvement included: recognition by men of the impact of their
      involvement, pride, advocacy, incentives and disincentives and male champions.
      Barriers included socio-cultural beliefs, stigmatisation and opportunity costs.
      The study also found that there were several limitations that had unintended
      consequences on desired programme outcomes. These included: discriminating
      against women, marginalisation of married women and reinforcing men's decision
      making roles. CONCLUSION: The study findings highlight the importance of
      involving men in maternal and child health for improved nutrition outcomes. We
      emphasise the need for nutrition policy-makers to be aware that gender dynamics
      are changing. It is no longer just women who are involved in nutrition
      activities, therefore policy-makers need to revise their approach to ensure that
      they consider men's role in nutrition.

PMID- 29351779
TI  - The effect of twin-to-twin delivery time intervals on neonatal outcome for second
      twins.
AB  - BACKGROUND: The objective was to examine the effect of twin-to-twin delivery
      intervals on neonatal outcome for second twins. METHODS: This was a
      retrospective, hospital-based study, performed at a university teaching hospital
      in Western Sweden. Twin deliveries between 2008 and 2014 at >=32 + 0 weeks of
      gestation, where the first twin was delivered vaginally, were included. Primary
      outcome was a composite outcome of metabolic acidosis, Apgar < 4 at 5 min or
      peri/neonatal mortality in the second twin. Secondary outcome was a composite
      outcome of neonatal morbidity. RESULTS: A total of 527 twin deliveries were
      included. The median twin-to-twin delivery interval time was 19 min (range 2-399
      min) and 68% of all second twins were delivered within 30 min. Primary outcome
      occurred in 2.6% of the second twins. Median twin-to-twin delivery interval was
      34 min (8-78 min) for the second twin with a primary outcome, and 19 min (2-399
      min) for the second twin with no primary outcome (p = 0.028). Second twins
      delivered within a twin-to-twin interval of 0-30 min had a higher pH in umbilical
      artery blood gas than those delivered after 30 min (pH 7.23 and pH 7.20, p < 
      0.0001). Secondary outcome was not associated with twin-to-twin delivery interval
      time. The combined vaginal-cesarean delivery rate was 6.6% (n = 35) and the rate
      was higher with twin-to-twin delivery interval >  30 min (p <  0.0001).
      CONCLUSIONS: An association, but not necessarily a causality, between twin-to
      twin delivery interval and primary outcome was seen. An upper time limit on twin
      to-twin delivery time intervals may be justified. However, the optimal time
      interval needs further studies.

PMID- 29351780
TI  - FANCM and RECQL genetic variants and breast cancer susceptibility: relevance to
      South Poland and West Ukraine.
AB  - BACKGROUND: FANCM and RECQL have recently been reported as breast cancer
      susceptibility genes and it has been suggested that they should be included on
      gene panel tests for breast cancer predisposition. However, the clinical value of
      testing for mutations in RECQL and FANCM remains to be determined. In this study,
      we have characterised the spectrum of FANCM and RECQL mutations in women affected
      with breast or ovarian cancer from South-West Poland and West Ukraine. METHODS:
      We applied Hi-Plex, an amplicon-based enrichment method for targeted massively
      parallel sequencing, to screen the coding exons and proximal intron-exon
      junctions of FANCM and RECQL in germline DNA from unrelated women affected with
      breast cancer (n = 338) and ovarian cancer (n = 89) from Poland (n = 304) and
      Ukraine (n = 123). These women were at high-risk of carrying a genetic
      predisposition to breast and/or ovarian cancer due to a family history and/or
      early-onset disease. RESULTS: Among 427 women screened, we identified one carrier
      of the FANCM:c.1972C > T nonsense mutation (0.23%), and two carriers of the
      frameshift insertion FANCM:c.1491dup (0.47%). None of the variants we observed in
      RECQL were predicted to be loss-of-function mutations by standard variant effect
      prediction tools. CONCLUSIONS: Our study of the Polish and Ukrainian populations
      has identified a carrier frequency of truncating mutations in FANCM consistent
      with previous reports. Although initial reports suggesting that mutations in
      RECQL could be associated with increased breast cancer risk included women from
      Poland and identified the RECQL:c.1667_1667 + 3delAGTA mutation in 0.23-0.35% of
      breast cancer cases, we did not observe any carriers in our study cohort.
      Continued screening, both in research and diagnostic settings, will enable the
      accumulation of data that is needed to establish the clinical utility of
      including RECQL and FANCM on gene panel tests.

PMID- 29351781
TI  - MINDMAP: establishing an integrated database infrastructure for research in
      ageing, mental well-being, and the urban environment.
AB  - BACKGROUND: Urbanization and ageing have important implications for public mental
      health and well-being. Cities pose major challenges for older citizens, but also
      offer opportunities to develop, test, and implement policies, services,
      infrastructure, and interventions that promote mental well-being. The MINDMAP
      project aims to identify the opportunities and challenges posed by urban
      environmental characteristics for the promotion and management of mental well
      being and cognitive function of older individuals. METHODS: MINDMAP aims to
      achieve its research objectives by bringing together longitudinal studies from 11
      countries covering over 35 cities linked to databases of area-level environmental
      exposures and social and urban policy indicators. The infrastructure supporting
      integration of this data will allow multiple MINDMAP investigators to safely and
      remotely co-analyse individual-level and area-level data. Individual-level data
      is derived from baseline and follow-up measurements of ten participating cohort
      studies and provides information on mental well-being outcomes, sociodemographic
      variables, health behaviour characteristics, social factors, measures of frailty,
      physical function indicators, and chronic conditions, as well as blood derived
      clinical biochemistry-based biomarkers and genetic biomarkers. Area-level
      information on physical environment characteristics (e.g. green spaces,
      transportation), socioeconomic and sociodemographic characteristics (e.g.
      neighbourhood income, residential segregation, residential density), and social
      environment characteristics (e.g. social cohesion, criminality) and national and
      urban social policies is derived from publically available sources such as
      geoportals and administrative databases. The linkage, harmonization, and analysis
      of data from different sources are being carried out using piloted tools to
      optimize the validity of the research results and transparency of the
      methodology. DISCUSSION: MINDMAP is a novel research collaboration that is
      combining population-based cohort data with publicly available datasets not
      typically used for ageing and mental well-being research. Integration of various
      data sources and observational units into a single platform will help to explain
      the differences in ageing-related mental and cognitive disorders both within as
      well as between cities in Europe, the US, Canada, and Russia and to assess the
      causal pathways and interactions between the urban environment and the individual
      determinants of mental well-being and cognitive ageing in older adults.

PMID- 29351782
TI  - Stakeholders' perspectives on facilitators of and barriers to the utilisation of
      and access to maternal health services in Eritrea: a qualitative study.
AB  - BACKGROUND: Wars affect maternal health services by destroying health systems.
      Eritrea experienced two wars with neighbouring Ethiopia. Despite this, the
      maternal mortality ratio (MMR) in Eritrea fell by 69% from 1590 per 100,000 live
      births in 1990 to 501 in 2015. This study aimed to examine facilitators of and
      barriers to the utilisation of and access to maternal health services in Eritrea.
      METHODS: Using in-depth interviews and field observations for data collection,
      this qualitative study was conducted in five healthcare facilities in Asmara, the
      capital of Eritrea, in February and March 2016. The participants were: women (n =
      40), husbands (n = 5), healthcare providers (n = 10), and decision makers (n =
      5). RESULTS: There were two perceived facilitators of utilisation of and access
      to maternal health services: health education (related to the WHO health service
      delivery building blocks) and improvement in gender equality driven by the role
      played by Eritrean women as combatants during the War of Independence (1961
      1991). The only perceived barrier was poor quality of care due to lack of
      ultrasound machines, short clinic opening hours, and shortage of healthcare
      workers (related to the WHO health workforce building block). CONCLUSION: This
      study assessed women and their husbands/partners' perceptions and the possible
      effects of contemporary Eritrean culture and the history of war on the
      utilisation of and access to maternal health services in the country. As well, we
      examined healthcare providers' and decision makers' perspectives. The two key
      facilitators of women's utilisation of and access to maternal health services
      were health education and women's empowerment driven by their role as combatants
      during the War of Independence. One main barrier was poor quality of care due to
      lack of ultrasound machines, short clinic opening hours, and a shortage of
      healthcare workers. As only a limited number of qualitative studies have been
      published about maternal health services in war-affected sub-Saharan African
      countries, our findings regarding health education and women's empowerment could
      be considered in other war-affected countries similar to Eritrea. Nevertheless,
      further research is needed to investigate our findings - particularly regarding
      female empowerment driven by women's role in combat in relation to their maternal
      health.

PMID- 29351783
TI  - Simple citrate anticoagulation protocol for low flux haemodialysis.
AB  - BACKGROUND: For patients unable to receive heparin anticoagulation during
      haemodialysis, saline flushes to reduce circuit clotting are often the norm.
      Regional citrate anticoagulation (RCA) although effective is not used by many
      centres including in Singapore. We wanted to demonstrate the superiority and
      safety of a simple regional citrate anticoagulation regime, compared to saline
      flushes, for heparin-free low flux haemodialysis. METHODS: This is a prospective,
      open label, cross over study on 25 sequential haemodialysis sessions for
      inpatients receiving heparin-free haemodialysis. Patients were allocated either
      to regional citrate anticoagulation or standard heparin free haemodialysis and
      subsequently cross over to the alternate method. RCA was carried out using a
      protocol derived from previous studies. Assessment of anticoagulation was
      performed using visual inspection of clot formation in dialysis circuits and post
      filter ionized calcium (iCa2+) using point-of-care Ionized calcium device at
      stipulated intervals. Intravenous Calcium gluconate replacement was given to
      patients receiving citrate adjusting the rate according to pre-filter iCa2+.
      Laboratory analyses of electrolytes were also assessed at the start and end of
      the RCA sessions. RESULTS: There were no clots in the RCA arm, with 79% (n = 19)
      in the saline flush arm having some clot, including 1 clotted circuit. Post
      filter iCa2+ at various time points were within acceptable range. Electrolyte
      readings in the RCA group were all within normal limits except for 4 cases of
      total Calcium:iCa2+ ratio > 2.5. CONCLUSION: RCA is confirmed to be superior to
      saline flushes for circuit patency. We have a simple and safe protocol that can
      be followed for low flux haemodialysis. The study was approved by Singapore
      National Health Group domain-specific ethnical committee. NHG DSRB reference
      number 2014/01037. TRIAL REGISTRATION: Trial registration number: ISRCTN69952745
      (registration date 8/11/17).

PMID- 29351784
TI  - Predictors of quality of life among inpatients in forensic mental health:
      implications for occupational therapists.

PMID- 29351785
TI  - Theorizing the complexity of HIV disclosure in vulnerable populations: a grounded
      theory study.
AB  - BACKGROUND: HIV disclosure is an important step in delivering the right care to
      people. However, many people with an HIV positive status choose not to disclose.
      This considerably complicates the delivery of adequate health care. METHODS: We
      conducted a grounded theory study to develop a theoretical model explaining how
      local contexts impact on HIV disclosure and what the mechanisms are that
      determine whether people choose to disclose or not. We conducted in-depth
      interviews among 23 people living with HIV, 8 health workers and 5 family and
      community members, and 1 community development worker in Achham, Nepal. Data were
      analysed using constant-comparative method, performing three levels of open,
      axial, and selective coding. RESULTS: Our theoretical model illustrates how two
      dominant systems to control HIV, namely a community self-coping and a public
      health system, independently or jointly, shape contexts, mechanisms and outcomes
      for HIV disclosure. CONCLUSION: This theoretical model can be used in
      understanding processes of HIV disclosure in a community where HIV is
      concentrated in vulnerable populations and is highly stigmatized, and in
      determining how public health approaches would lead to reduced stigma levels and
      increased HIV disclosure rates.

PMID- 29351786
TI  - Factors associated with intended use of a maternity waiting home in Southern
      Ethiopia: a community-based cross-sectional study.
AB  - BACKGROUND: Although Ethiopia is scaling up Maternity Waiting Homes (MWHs) to
      reduce maternal and perinatal mortality, women's use of MWHs varies markedly
      between facilities. To maximize MWH utilization, it is essential that
      policymakers are aware of supportive and inhibitory factors. This study had the
      objective to describe factors and perceived barriers associated with potential
      utilization of an MWH among recently delivered and pregnant women in Southern
      Ethiopia. METHODS: A community-based cross-sectional study was conducted between
      March and November 2014 among 428 recently delivered and pregnant women in the
      Eastern Gurage Zone, Southern Ethiopia, where an MWH was established for high
      risk pregnant women to await onset of labour. The structured questionnaire
      contained questions regarding possible determinants and barriers. Logistic
      regression with 95% Confidence Intervals (CI) was used to examine association of
      selected variables with potential MWH use. RESULTS: While only thirty women
      (7.0%) had heard of MWHs prior to the study, 236 (55.1%), after being explained
      the concept, indicated that they intended to stay at such a structure in the
      future. The most important factors associated with intended MWH use in the
      bivariate analysis were a woman's education (secondary school or higher vs. no
      schooling: odds ratio [OR] 6.3 [95% CI 3.46 to 11.37]), her husband's education
      (secondary school or higher vs. no schooling: OR 5.4 [95% CI 3.21 to 9.06]) and
      envisioning relatively few barriers to MWH use (OR 0.32 [95% CI 0.25 to 0.39]).
      After adjusting for possible confounders, potential users had more frequently
      suffered complications in previous childbirths (adjusted odds ratio [aOR] 4.0
      [95% CI 1.13 to 13.99]) and envisioned fewer barriers to MWH use (aOR 0.3 [95% CI
      0.23 to 0.38]). Barriers to utilization included being away from the household
      (aOR 18.1 [95% CI 5.62 to 58.46]) and having children in the household cared for
      by the community during a woman's absence (aOR 9.3 [95% CI 2.67 to 32.65]).
      CONCLUSIONS: Most respondents had no knowledge about MWHs. Having had
      complications during past births and envisioning few barriers were factors found
      to be positively associated with intended MWH use. Unless community awareness of
      preventive maternity care increases and barriers for women to stay at MWHs are
      overcome, these facilities will continue to be underutilized, especially among
      marginalized women.

PMID- 29351787
TI  - SCL20A2 mutation presenting with acute ischemic stroke: a case report.
AB  - BACKGROUND: Primary familial brain calcification (PFBC) is a rare disorder
      characterized by distinctive bilateral brain calcification and variable clinical
      presentations. However, cerebrovascular attack was rarely reported in PFBC
      patients. We here reported a SLC20A2 mutation patient presenting with acute
      ischemic stroke. CASE PRESENTATION: A 56 years old man was transferred to our
      hospital because of 6 days of melena and 3 days of somnolence, agitation and mood
      changes. Computed tomography (CT) scan showed symmetrical calcifications in
      bilateral basal ganglia, caudate nucleus, thalami, subcortical white matter and
      cerebellum, which is consistent with PFBC. Brain magnetic resonance imaging (MRI)
      revealed acute ischemic stroke in bilateral basal ganglia and periventricular
      regions. Mutational analysis identified a SLC20A2 gene mutation c.344C > T
      (p.Thr115Met) in exon 3. One of his daughters had also suffered from brain
      calcification. MR perfusion imaging revealed hypoperfusion in bilateral basal
      ganglia, prefrontal and temporal lobe. After treatment, he discharged with a
      favorable functional outcome but cognitive impairment. CONCLUSIONS: Ischemic
      stroke can occur in PFBC patients, which may be associated with hypoperfusion and
      calcification of arteries. And hypoperfusion in frontotemporal lobar may be
      related with their cognitive impairment.

PMID- 29351788
TI  - Elevated inflammatory cytokines in aqueous cytokine profile in HIV-1 infected
      patients with cataracts in Uganda.
AB  - BACKGROUND: Cataracts occur earlier among HIV-infected adults and this is
      attributed to various intraocular inflammatory processes that result in early
      degeneration. In this study we purposed to investigate whether HIV infected
      individuals with cataracts develop heightened intraocular inflammatory processes
      compared to their HIV negative counterparts by determining the concentration of 8
      cytokines in the aqueous humour of HIV-positive adults with cataracts and their
      HIV-negative counterparts. METHODS: A cross-sectional study was conducted among
      consecutive adults with cataracts that were operated in an ophthalmology surgical
      camp in western Uganda. We determined levels of Granulocyte macrophage
      stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour
      necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4),
      interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a
      multiplexed cytokine analysis. Data was entered in the SPSS version 10 and
      analyzed using STATA statistical software version 7.0. Categorical and continuous
      variables were compared using the chi2 test, Fisher's exact test and the
      Student's t-test. Bonferroni correction was used to cater for multiple comparison
      of p values for the various cytokines. RESULTS: The 50 adults that underwent
      cataract surgery were outdoor peasants with similar exposure hours to UV
      radiation. The HIV-positive patients were younger {median age 43 years (SD
      11.741)} compared to the HIV -negative patients {median age 66.5 years (SD
      21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells
      /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory
      cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive
      individuals (p = 0.001, 0.030, < 0.001 respectively). HIV-positive individuals on
      ART also showed significantly higher levels of GM-CSF, IL-8 and IL - 10 (p =
      0.002, 0.021, < 0.001 respectively). TNF-a and IL-4 were significantly higher
      among those with a CD4+ T cell count greater than 200cells/mm3 compared to those
      with CD4+ T cell count less than 200 cells/mm3 (p = 0.022, 0.032 respectively).
      CONCLUSION: Cataracts among HIV-positive adults were associated with higher
      intraocular inflammation relative to the healthy elderly individuals with
      cataracts. There is need to explore the potential role of intra-ocular anti
      inflammatory agents in the management of cataracts among HIV positive patients.

PMID- 29351789
TI  - Prevention of severe infectious complications after colorectal surgery using
      preoperative orally administered antibiotic prophylaxis (PreCaution): study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Colorectal surgery is frequently complicated by surgical site
      infections (SSIs). The most important consequences of SSIs are prolonged
      hospitalization, an increased risk of surgical reintervention and an increase in
      mortality. Perioperative intravenously administered antibiotic prophylaxis is the
      standard of care to reduce the risk of SSIs. In the last few decades,
      preoperative orally administered antibiotics have been suggested as additional
      prophylaxis to further reduce the risk of infection, but are currently not part
      of routine practice in most hospitals. The objective of this study is to evaluate
      the efficacy of a preoperative orally administered antibiotic prophylaxis (Pre
      OP) in addition to intravenously administered perioperative antibiotic
      prophylaxis to reduce the incidence of deep SSIs and/or mortality after elective
      colorectal surgery. METHODS/DESIGN: The PreCaution trial is designed as a
      multicenter, double-blind, randomized, placebo-controlled clinical trial that
      will be carried out in The Netherlands. Adult patients who are scheduled for
      elective colorectal surgery are eligible to participate. In total, 966 patients
      will be randomized to receive the study medication. This will either be Pre-OP, a
      solution that consists of tobramycin and colistin sulphate, or a placebo
      solution. The study medication will be administered four times daily during the 3
      days prior to surgery. Perioperative intravenously administered antibiotic
      prophylaxis will be administered to all patients in accordance with national
      infection control guidelines. The primary endpoint of the study is the cumulative
      incidence of deep SSIs and/or mortality within 30 days after surgery. Secondary
      endpoints include both infectious and non-infectious complications of colorectal
      surgery, and will be evaluated 30 days and/or 6 months after surgery. DISCUSSION:
      To date, conclusive evidence on the added value of preoperative orally
      administered antibiotic prophylaxis in colorectal surgery is lacking. The
      PreCaution trial should determine the effects of orally administered antibiotics
      in preventing infectious complications in elective colorectal surgery. TRIAL
      REGISTRATION: Netherlands Trial Register, ID: NTR6113 . Registered on 11 October
      2016; EudraCT 2015-005736-17.

PMID- 29351790
TI  - Development of a framework to improve the process of recruitment to randomised
      controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised)
      framework.
AB  - BACKGROUND: Research has shown that recruitment to trials is a process that
      stretches from identifying potentially eligible patients, through eligibility
      assessment, to obtaining informed consent. The length and complexity of this
      pathway means that many patients do not have the opportunity to consider
      participation. This article presents the development of a simple framework to
      document, understand and improve the process of trial recruitment. METHODS: Eight
      RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial,
      feasibility or pilot study. Part of the QRI required mapping the patient
      recruitment pathway using trial-specific screening and recruitment logs. A
      content analysis compared the logs to identify aspects of the recruitment pathway
      and process that were useful in monitoring and improving recruitment. Findings
      were synthesised to develop an optimised simple framework that can be used in a
      wide range of RCTs. RESULTS: The eight trials recorded basic information about
      patients screened for trial participation and randomisation outcome. Three trials
      systematically recorded reasons why an individual was not enrolled in the trial,
      and further details why they were not eligible or approached, or declined
      randomisation. A framework to facilitate clearer recording of the recruitment
      process and reasons for non-participation was developed: SEAR - Screening, to
      identify potentially eligible trial participants; Eligibility, assessed against
      the trial protocol inclusion/exclusion criteria; Approach, the provision of oral
      and written information and invitation to participate in the trial, and
      Randomised or not, with the outcome of randomisation or treatment received.
      CONCLUSIONS: The SEAR framework encourages the collection of information to
      identify recruitment obstacles and facilitate improvements to the recruitment
      process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely
      to add most value in trials where recruitment problems are anticipated or
      evident. Further work to test it more widely is recommended.

PMID- 29351791
TI  - Efficacy of electrical acupuncture on vascular cognitive impairment with no
      dementia: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Vascular cognitive impairment with no dementia (VCIND), manifested
      mainly as mild impairment of concentration and executive function, is the early
      phase of vascular dementia (VD). Currently, there is no specific treatment for
      VCIND. We hypothesize that electrical acupuncture can improve the mental and
      motor functions of patients with VCIND. Thus, we designed this randomized
      controlled trial to test this hypothesis by comparing the therapeutic effect of
      electrical acupuncture versus sham acupuncture in patients with VCIND.
      METHOD/DESIGN: In this single-center 3-year study, 120 eligible patients will be
      recruited and randomly assigned to receive electrical acupuncture treatment (n =
      60) or sham acupuncture (n = 60) for 8 consecutive weeks (24 sessions in total),
      with the same acupoint prescription (DU20, EX-HN3, DU24, DU17, DU26, EX-HN1, HT7,
      PC6, GB20, SP6). The primary assessment is the Montreal Cognitive Assessment. The
      secondary assessments are the Modified Barthel Index and Event-Related Potential.
      All outcomes will be assessed at baseline, endpoint, and follow-up at 8 and 24
      weeks after the end of treatment. DISCUSSION: If the outcome confirms the
      effectiveness and safety of electrical acupuncture in treating VCIND, this
      treatment is expected to be promoted in clinical practice to treat such patients.
      TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR-IIR
      17011513 ; Registered on 27 May 2017.

PMID- 29351792
TI  - Successful recruitment to trials: findings from the SCIMITAR+ Trial.
AB  - BACKGROUND: Randomised controlled trials (RCT) can struggle to recruit to target
      on time. This is especially the case with hard to reach populations such as those
      with severe mental ill health. The SCIMITAR+ trial, a trial of a bespoke smoking
      cessation intervention for people with severe mental ill health achieved their
      recruitment ahead of time and target. This article reports strategies that helped
      us to achieve this with the aim of aiding others recruiting from similar
      populations. METHODS: SCIMITAR+ is a multi-centre pragmatic two-arm parallel
      group RCT, which aimed to recruit 400 participants with severe mental ill health
      who smoke and would like to cut down or quit. The study recruited primarily in
      secondary care through community mental health teams and psychiatrists with a
      smaller number of participants recruited through primary care. Recruitment opened
      in October 2015 and closed in December 2016, by which point 526 participants had
      been recruited. We gathered information from recruiting sites on strategies which
      led to the successful recruitment in SCIMITAR+ and in this article present our
      approach to trial management along with the strategies employed by the recruiting
      sites. RESULTS: Alongside having a dedicated trial manager and trial management
      team, we identified three main themes that led to successful recruitment. These
      were: clinicians with a positive attitude to research; researchers and clinicians
      working together; and the use of NHS targets. The overriding theme was the
      importance of relationships between both the researchers and the recruiting
      clinicians and the recruiting clinicians and the participants. CONCLUSIONS: This
      study makes a significant contribution to the limited evidence base of real-world
      cases of successful recruitment to RCTs and offers practical guidance to those
      planning and conducting trials. Building positive relationships between
      clinicians, researchers and participants is crucial to successful recruitment.

PMID- 29351793
TI  - Retinal complications of gout: a case report and review of the literature.
AB  - BACKGROUND: There have been few reported findings of posterior segment
      complications of gout. While exudative lesions, an increased risk of macular
      degeneration, and vascular occlusions have been previously reported, to our
      knowledge, refractile macular lesions have not been reported in a patient with
      chronic uncontrolled gout. CASE PRESENTATION: Highly refractile, crystal-like
      lesions were found in the macula of a 62 year old male patient with chronically
      uncontrolled gout. The lesions appeared at the termination of retinal arterioles
      and were located at the level of the retinal pigment epithelium. The lesions did
      not stain with fluorescein and were associated with larger areas geographic
      atrophy. Review of the patient's blood tests revealed well-controlled
      vasculopathic risk factors. Fundus appearance and best-corrected visual acuity
      remained stable over 12 months of follow-up during which the uric acid levels
      were well controlled. CONCLUSION: Retinopathy may be associated with chronically
      uncontrolled gout and patients with visual complaints should undergo a dilated
      examination in addition to the typical anterior segment slit-lamp exam.

PMID- 29351794
TI  - Metabolic syndrome severity is significantly associated with future coronary
      heart disease in Type 2 diabetes.
AB  - BACKGROUND: The severity of the metabolic syndrome (MetS) is significantly
      associated with future coronary heart disease (CHD) among individuals without
      baseline Type 2 diabetes. However, the validity of assessing MetS severity among
      individuals with diabetes is unknown. OBJECTIVE: To assess for differences in
      MetS severity by timing of Type 2 diabetes diagnosis and to assess for
      associations between MetS severity and future CHD among individuals with
      diabetes. METHODS: We analyzed data from participants of the Atherosclerosis Risk
      in Communities study, including 1419 with- and 7241 without diabetes, followed
      during 4 visits and adjudicated CHD diagnoses over a 20-year period. We used Cox
      regression techniques to assess hazard ratios (HR) of CHD based on a sex- and
      race/ethnicity-specific MetS-severity Z-score (standard MetS score) and a similar
      MetS-severity score formulated without incorporating glucose as a component of
      MetS (no-glucose MetS score). RESULTS: For both the standard- and no-glucose MetS
      severity scores, scores were highest in the baseline-diabetes group, lowest in
      the never-diabetes group and intermediate in the incident-diabetes groups. Among
      participants with diabetes, increasing MetS-severity score at baseline was
      associated with incident CHD, using both the standard MetS score (HR 1.29, 95%
      confidence interval [CI] 1.21, 1.39) and the no-glucose score (HR 1.42, CI 1.24,
      1.62) (both p < 0.001). For the baseline-diabetes group, this relationship
      remained significant when Visit 2 Hemoglobin-A1c was included in the model, both
      for the standard MetS score (HR 1.21, CI 1.09, 1.34; p < 0.001) and the no
      glucose score (HR 1.25, CI 1.04, 1.51; p = 0.02). CONCLUSIONS: MetS severity
      appears to provide an estimate of metabolic disarray in the setting of diabetes
      and is predictive of future CHD events beyond HbA1c. Identifying MetS severity
      among individuals with diabetes may help in identifying those at higher risk, who
      could then receive further preventative treatment.

PMID- 29351795
TI  - Malaria knowledge and bed net use in three transmission settings in southern
      Africa.
AB  - BACKGROUND: Insecticide-treated nets (ITNs) reduce malaria morbidity and
      mortality in endemic areas. Despite increasing availability, the use of ITNs
      remains limited in some settings. Poor malaria knowledge is a barrier to the
      widespread use of ITNs. The goal of this study was to assess the levels of
      malaria knowledge and evaluate factors associated with bed net use among
      individuals residing in three regions of southern Africa with different levels of
      malaria transmission and control. METHODS: A cross-sectional study was conducted
      on a sample of 7535 residents recruited from 2066 households in Mutasa District,
      Zimbabwe (seasonal malaria transmission), Choma District, Zambia (low
      transmission) and Nchelenge District, Zambia (high transmission), between March
      2012 and March 2017. A standardized questionnaire was used to collect data on
      demographics, malaria-related knowledge and use of preventive measures.
      Multivariate logistic regression analyses were used to assess determinants of bed
      net use. RESULTS: Most of the 3836 adult participants correctly linked mosquito
      bites to malaria (85.0%), mentioned at least one malaria symptom (95.5%) and knew
      of the benefit of sleeping under an ITN. Bed net ownership and use were highest
      in Choma and Nchelenge Districts and lowest in Mutasa District. In multivariate
      analyses, knowledge of ITNs was associated with a 30-40% increased likelihood of
      bed net use after adjusting for potential confounders across all sites. Other
      factors significantly associated with bed net use were age, household size and
      socioeconomic status, although the direction, strength and size of association
      varied by study site. Importantly, participants aged 5-14 years had reduced odds
      of sleeping under a bed net compared to children younger than 5 years.
      CONCLUSION: Relevant knowledge of ITNs translated into the expected preventive
      behaviour of sleeping under a bed net, underscoring the need for continued health
      messaging on malaria prevention. The implementation and delivery of malaria
      control and elimination interventions needs to consider socioeconomic equity
      gaps, and target school-age children to ensure access to and improve utilization
      of ITNs.

PMID- 29351796
TI  - The Jun/miR-22/HuR regulatory axis contributes to tumourigenesis in colorectal
      cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is a severe health problem worldwide.
      Clarifying the mechanisms for the deregulation of oncogenes and tumour
      suppressors in CRC is vital for its diagnosis, treatment, prognosis and
      prevention. Hu antigen R (HuR), which is highly upregulated in CRC, functions as
      a pivotal oncogene to promote CRC progression. However, the underlying cause of
      its dysregulation is poorly understood. METHODS: In CRC tissue sample pairs, HuR
      protein levels were measured by Western blot and immunohistochemical (IHC)
      staining, respectively. HuR mRNA levels were also monitored by qRT-PCR. Combining
      meta-analysis and microRNA (miRNA) target prediction software, we predicted
      miRNAs that targeted HuR. Pull-down assay, Western blot and luciferase assay were
      utilized to demonstrate the direct binding of miR-22 on HuR's 3'-UTR. The
      biological effects of HuR and miR-22 were investigated both in vitro by CCK-8,
      EdU and Transwell assays and in vivo by a xenograft mice model. JASPAR and
      SABiosciences were used to predict transcriptional factors that could affect miR
      22. Luciferase assay was used to explore the validity of putative Jun binding
      sites for miR-22 regulation. ChIP assay was performed to test the Jun's occupancy
      on the C17orf91 promoter. RESULTS: We observed a significant upregulation of HuR
      in CRC tissue pairs and confirmed the oncogenic function of HuR both in vitro and
      in vivo. We found that an important tumour-suppressive miRNA, miR-22, was
      significantly downregulated in CRC tissues and inversely correlated with HuR in
      both CRC tissues and CRC cell lines. We demonstrated that miR-22 directly bound
      to the 3'-UTR of HuR and led to inhibition of HuR protein, which repressed CRC
      proliferation and migration in vitro and decelerated CRC xenografted tumour
      growth in vivo. Furthermore, we found that the onco-transcription factor Jun
      could inhibit the transcription of miR-22. CONCLUSIONS: Our findings highlight
      the critical roles of the Jun/miR-22/HuR regulatory axis in CRC progression and
      may provide attractive potential targets for CRC prevention and treatment.

PMID- 29351797
TI  - Evaluating the impact of a quality management intervention on post-abortion
      contraceptive uptake in private sector clinics in western Kenya: a pre- and post
      intervention study.
AB  - BACKGROUND: Integration of family planning counselling and method provision into
      safe abortion services is a key component of quality abortion care. Numerous
      barriers to post-abortion family planning (PAFP) uptake exist. This study aimed
      to evaluate the effect of a quality management intervention for providers on PAFP
      uptake. METHODS: We conducted a pre- and post-intervention study between November
      2015 and July 2016 in nine private clinics in Western Kenya. We collected
      baseline and post-intervention data using in-person interviews on the day of
      procedure, and follow-up telephone interviews to measure contraceptive uptake in
      the 2 weeks following abortion. We also conducted semi-structured interviews with
      providers. The intervention comprised a 1-day orientation, a counselling job
      aide, and enhanced supervision visits. The primary outcome was the proportion of
      clients receiving any method of PAFP (excluding condoms) within 14 days of
      obtaining an abortion. Secondary outcomes were the proportion of clients
      receiving PAFP counselling, and the proportion of clients receiving long-acting
      reversible contraception (LARC) within 14 days of the service. We used chi
      squared tests and multivariate logistic regression to determine whether there
      were significant differences between baseline and post-intervention, adjusting
      for potential confounding factors and clustering at the clinic level. RESULTS:
      Interviews were completed with 769 women, and 54% (414 women) completed a follow
      up telephone interview. Reported quality of counselling and satisfaction with
      services increased between baseline and post-intervention. Same-day uptake of
      PAFP was higher at post-intervention compared to baseline (aOR 1.94, p < 0.001),
      as was same-day uptake of LARC (aOR 1.72, p < 0.001). There was no overall
      increase in uptake of PAFP 2 weeks following abortion. Providers reported mixed
      opinions about the effectiveness of the intervention but most reported that the
      supervision visits helped them improve the quality of their services.
      CONCLUSIONS: A quality management intervention was successful in improving the
      quality of PAFP counselling and provision. Uptake of same-day PAFP, including
      LARC, increased, but there was no increase in overall uptake of PAFP 2 weeks
      after the abortion.

PMID- 29351798
TI  - Comparative salivary proteomics analysis of children with and without dental
      caries using the iTRAQ/MRM approach.
AB  - BACKGROUND: Dental caries is a major worldwide oral disease afflicting a large
      proportion of children. As an important host factor of caries susceptibility,
      saliva plays a significant role in the occurrence and development of caries. The
      aim of the present study was to characterize the healthy and cariogenic salivary
      proteome and determine the changes in salivary protein expression of children
      with varying degrees of active caries, also to establish salivary proteome
      profiles with a potential therapeutic use against dental caries. METHODS: In this
      study, unstimulated saliva samples were collected from 30 children (age 10-12
      years) with no dental caries (NDC, n = 10), low dental caries (LDC, n = 10), and
      high dental caries (HDC, n = 10). Salivary proteins were extracted, reduced,
      alkylated, trypsin digested and labeled with isobaric tags for relative and
      absolute quantitation, and then they were analyzed with GO annotation, biological
      pathway analysis, hierarchical clustering analysis, and protein-protein
      interaction analysis. Targeted verifications were then performed using multiple
      reaction monitoring mass spectrometry. RESULTS: A total of 244 differentially
      expressed proteins annotated with GO annotation in biological processes, cellular
      component and molecular function were identified in comparisons among children
      with varying degrees of active caries. A number of caries-related proteins as
      well as pathways were identified in this study. As compared with caries-free
      children, the most significantly enriched pathways involved by the up-regulated
      proteins in LDC and HDC were the ubiquitin mediated proteolysis pathway and
      African trypanosomiasis pathway, respectively. Subsequently, we selected 53
      target proteins with differential expression in different comparisons, including
      mucin 7, mucin 5B, histatin 1, cystatin S and cystatin SN, basic salivary proline
      rich protein 2, for further verification using MRM assays. Protein-protein
      interaction analysis of these proteins revealed complex protein interaction
      networks, indicating synergistic action of salivary proteins in caries resistance
      or cariogenicity. CONCLUSIONS: Overall, our results afford new insight into the
      salivary proteome of children with dental caries. These findings might have
      bright prospect in future in developing novel biomimetic peptides with preventive
      and therapeutic benefits for childhood caries.

PMID- 29351799
TI  - Effect of the replacement of dietary vegetable oils with a low dose of
      extravirgin olive oil in the Mediterranean Diet on cognitive functions in the
      elderly.
AB  - BACKGROUND: Numerous studies have investigated the role of the monounsaturated
      fatty acid and other dietary factors in the prevention of cognitive decline but
      the short-term effect of a low dose of extravirgin olive oil on cognitive
      performances in the elderly have not still been investigated. Our aim was to
      investigate whether the replacement of all vegetable oils with a lower amount of
      extravirgin olive oil, in the contest of a Mediterranean Diet, would improve
      cognitive performances, among elderly Italian individuals. METHODS: 180 elderly
      individuals were randomly assigned to these treatment groups for 1 year: (1)
      MedDiet plus extravirgin OO, 20-30 g/day; (2) control MedDiet. The cognitive sub
      test of ADAScale was used to detect cognitive decline progression over 12 months.
      RESULTS: ADAS-cog score variation after 1 year, adjusted for food groups which
      were different between groups, was - 1.6 +/- 0.4 and - 3.0 +/- 0.4 in the MedDiet
      and MedDiet plus extravirgin OO groups, respectively (p = 0.024). Extravirgin OO
      intake was 30 g +/- 12 and 26 g +/- 6 in the MedDiet and MedDiet plus extravirgin
      OO groups, respectively (p = 0.044). CONCLUSIONS: We demonstrated the higher
      short-term improvement of cognitive functions scores in individuals of the
      MedDiet plus low dose of extravirgin olive oil rather than MedDiet alone.
      Extravirgin olive oil is the best quality oil and may have a neuroprotective
      effect.

PMID- 29351800
TI  - Drug resistance genes: pvcrt-o and pvmdr-1 polymorphism in patients from malaria
      endemic South Western Coastal Region of India.
AB  - BACKGROUND: Malaria is highly prevalent in many parts of India and is mostly
      caused by the parasite species Plasmodium vivax followed by Plasmodium
      falciparum. Chloroquine (CQ) is the first-line treatment for blood stage P. vivax
      parasites, but cases of drug resistance to CQ have been reported from India. One
      of the surveillance strategies which is used to monitor CQ drug resistance, is
      the analysis of single nucleotide polymorphisms (SNPs) of the associated gene
      markers. Susceptibility to CQ can also be determined by copy number assessment of
      multidrug resistant gene (mdr-1). The current study has examined the prevalence
      of SNPs in P. vivax orthologs of P. falciparum chloroquine resistant and multi
      drug resistant genes (pvcrt-o and pvmdr-1, respectively) and pvmdr-1 copy number
      variations in isolates from the highly endemic Mangaluru city near the South
      Western Coastal region of India. METHODS: A total of 140 blood samples were
      collected from P. vivax infected patients attending Wenlock Hospital Mangaluru
      during July 2014 to January 2016. Out of these 140 samples, sequencing was
      carried out for 54 (38.5%) and 85 (60.7%) isolates for pvcrt-o and pvmdr-1,
      respectively. Single nucleotide polymorphisms (SNPs) in the pvcrt-o and pvmdr-1
      genes were analysed by direct sequencing method, while copy number variations of
      60 isolates (42. 8%) were determined by real time PCR. RESULTS: Out of 54
      clinical isolates analysed for pvcrt-o, three (5.6%) showed K10 insertion and the
      rest had wild type sequence. This is the first report to show K10 insertion in P.
      vivax isolates from India. Further, out of 85 clinical isolates of P. vivax
      analysed for mutations in pvmdr-1 gene, only one isolate had wild type sequence
      (~ 1%) while the remaining (99%) carried mutant alleles. Seven non-synonymous
      mutations with two novel mutations (I946V and Y1028C) were observed. Of all the
      observed mutations in pvmdr-1 gene, T958M was most highly prevalent (present in
      90% of samples) followed by F1076L (76%), and Y976F (7%). Amplification of pvmdr
      1 gene was observed in 31.6% of the isolates, out of 60 amplified. CONCLUSION:
      The observed variations both in pvmdr-1 and pvcrt-o genes indicate a trend
      towards parasite acquiring CQ resistance in this endemic area.

PMID- 29351801
TI  - High expression of TMEM40 is associated with the malignant behavior and
      tumorigenesis in bladder cancer.
AB  - BACKGROUND: Bladder cancer (BCa) is one of the most common cancers in the urinary
      system among the world. Previous studies suggested that TMEM40 expression level
      was significantly associated with clinicopathological parameters including
      histological grade, clinical stage and pT status of bladder cancer. However, the
      molecular mechanism of TMEM40 in BCa remains poorly understood. METHODS: Real
      time quantitative RT-PCR (qRT-PCR) and western blot (WB) were used to examine the
      expression levels of TMEM40 in BCa tissues, paired non-cancer tissues and cell
      lines. A series of experiments, including CCK-8, wound healing, flow cytometry,
      transwell and EdU assays were performed to assess the effects of TMEM40 on cell
      proliferation, cell cycle and apoptosis, migration and invasion. In addition,
      tumor growth was evaluated in vivo using a xenogenous subcutaneously implant
      model. All statistical analyses were executed by using the SPSS 20.0 software.
      All experimental data from three independent experiments were analyzed by
      Student's t test and results were expressed as mean +/- standard deviation.
      RESULTS: In this study, we identified the role of TMEM40 in the tumorigenesis of
      bladder cancer and found that it was upregulated in bladder cancer tissues and
      cell lines, compared with their normal counterparts. The results demonstrated
      that effective silence of TMEM40 expression suppressed cell proliferation,
      blocked G1-to-S cell cycle transition, and inhibited cell migration and invasion
      in human bladder 5637 and EJ cell lines. Consistently, in vivo data showed that
      TMEM40 silencing could dramatically decreased tumor growth. Further study
      revealed that TMEM40 knockdown resulted in accumulation of p53 and p21 protein
      and decrease of c-MYC and cyclin D1 protein. CONCLUSION: These data suggest that
      TMEM40 represents a potential oncogene, which exert a crucial role in the
      proliferation and apoptosis via the p53 signaling pathway in BCa, thus probably
      serve as a novel candidate biomarker and a potential therapeutic target for
      patients with BCa.

PMID- 29351802
TI  - Objectively measured active transportation to school and other destinations among
      10-13 year olds.
AB  - BACKGROUND: Descriptive data on active transportation in children focuses on the
      trip to school and has relied on subjective reports. The purpose of this study
      was to use objective measures to describe total active transportation and active
      transportation to common destinations within children. METHODS: This was a
      descriptive study of 388 children aged 10-13 years from Kingston, Ontario,
      Canada. Participants wore a Garmin GPS watch during waking hours for seven days.
      Personal Activity Measurement Location System software used the GPS data to
      identify trips, time spent in each trip and the trip modality (walking, bicycle
      or vehicle). Google Maps software was used to identify trip destinations.
      RESULTS: A total of 8875 trips were identified. Most (69%) trips were made by
      vehicle; 25% were made by walking and 6% by bicycle. Mean time spent in active
      transportation was 10.3 min/day (95% CI: 7.4, 14.5). Time spent in active
      transportation was higher for boys (12.1 min/day [95% CI: 8.8, 17.0) than for
      girls (8.5 min/day [95% CI: 6.1, 12.0]) and increased from 7.7 min/day (95% CI:
      5.5, 11.1) at age 10 to 14.3 min/day (95% CI: 10.3, 19.9) at age 13. Time spent
      in active transportation was lower in the winter by comparison to the other
      seasons. The four most common active transportation destinations were the
      participant's home, school, other people's homes, and parks or greenspace with
      69%, 39%, 37% and 32% of participants walking or bicycling to these destinations
      at least once over the 7-day measurement period. CONCLUSION: Over 65% of trips
      made and time spent travelling occurred in a vehicle. When active transportation
      was used, the most common destinations were home, school, other people's homes,
      and parks.

PMID- 29351803
TI  - Psychometric properties and measurement equivalence of the Multidimensional
      Fatigue Syndrome Inventory- Short Form (MFSI-SF) amongst breast cancer and
      lymphoma patients in Singapore.
AB  - BACKGROUND: Currently, several fatigue measurement instruments are available to
      evaluate and measure cancer-related fatigue. Amongst them, Multidimensional
      Fatigue Syndrome Inventory-Short Form (MFSI-SF) is a self-reported instrument and
      a multidimensional scale that aims to capture the global, somatic, affective,
      cognitive and behavioural symptoms of fatigue. This study examines the
      psychometric properties and measurement equivalence of the English and Chinese
      versions of MFSI-SF in breast cancer and lymphoma patients in Singapore. METHODS:
      Patients were recruited from National Cancer Centre Singapore. Validity,
      reliability and responsiveness of MFSI-SF were evaluated in this study.
      Convergent validity was evaluated by correlating total and subscales of MFSI-SF
      to known related constructs in EORTC QLQ-C30. Known group validity was assessed
      based on patients' cancer stage, pain, insomnia and depression symptoms.
      Reliability was evaluated by Cronbach's alpha. Responsiveness analyses were
      performed with patients who have undergone at least one cycle of chemotherapy.
      Multiple regression was used to compare the total and subscale scores of MSFI-SF
      between the two language versions. RESULTS: Data from 246 (160 English and 86
      Chinese version) breast cancer and lymphoma patients were included in the study.
      Moderate to high correlations were observed between correlated MFSI-SF subscales
      and EORTC QLQ-C30 domains (|r| = 0.524 to 0.774) except for a poor correlation (r
      = 0.394) observed between MFSI-SF vigour subscale and EORTC QLQ-C30 role
      functioning subscale. Total MFSI-SF scores could differentiate between patients
      with higher depression, pain and insomnia status. Internal consistency of MFSI-SF
      was also high (alpha = 0.749 to 0.944). Moderate correlation was observed between
      change in total MFSI-SF score and change in fatigue symptom scale score and
      global QoL score on EORTC QLQ-C30 (|r| = 0.478 and 0.404 respectively). Poor
      correlations were observed between change in scores of hypothesised subscales
      (|r| = 0.202 to 0.361) except for a moderate correlation between change in MFSI
      SF emotional fatigue score and change in EORTC QLQ-C30 emotional functioning
      domain score. Measurement equivalence was established for all subscales and total
      MFSI-SF score except for the emotional and vigour subscales. CONCLUSIONS: This
      study supports the use of MFSI-SF as a reasonably valid scale with good internal
      consistency for measuring fatigue levels in the Singapore cancer population.

PMID- 29351804
TI  - A metastasized hepatocellular carcinoma in the capsule of an undescended testis
      in the right inguinal area: report of a rare case.
AB  - BACKGROUND: Hepatocellular Carcinoma (HCC) is the most common primary carcinoma
      of the liver, which mainly metastasizes through the portal vein system. CASE
      PRESENTATION: Here, we report an extremely rare case in which HCC metastasized to
      the capsule of an undescended testis in the right inguinal area of the patient. A
      tumor approximately 8.8 * 7.0 cm in size was found in the patient's liver during
      a health check-up. Initially, it was considered a metastatic tumor because the
      patient was found to have cryptorchidism, which had been left untreated before he
      presented to our hospital. The patient underwent a radical orchiectomy via
      inguinal approach, and the resected testis in the right inguinal region was
      examined via microscopy. The cancer cells were arranged in nests and showed
      abundant red or clear cytoplasm and marked nuclear atypia. Immunohistochemical
      staining showed that the tumor cells were positive for CK, CK8/18, AFP,
      hepatocyte, GCP3, but negative for PLAP, CD10, CD30, CD34, and vimentin.
      CONCLUSION: According to these findings, the tumor in the inguinal region was
      considered a metastatic HCC arising from the liver, rather than a seminoma that
      had originated in the undescended testis. We suggest that during the diagnosis of
      malignancies, metastatic tumors should always be considered in the differential
      diagnosis even if the original presentation is at rare metastatic sites or
      concurrent with other disease(s).

PMID- 29351805
TI  - Neuroprotection by chitosan nanoparticles in oxidative stress-mediated injury.
AB  - OBJECTIVE: Oxidative stress is a critical component of nervous system secondary
      injury. Oxidative stress produces toxic chemical byproducts including reactive
      aldehydes that traverse intact membranes and attack neighboring healthy cells.
      This secondary damage often leads to further patho-biochemical cascades that
      exacerbate the original insult. In this work, we investigate the therapeutic
      effects of chitosan nanoparticles on cell cultures exposed to oxidative stress.
      RESULTS: We found chitosan nanoparticles can rescue BV-2 glial cells from death,
      but only for cells undergoing necrosis. Necrosis occurred when cultures were
      challenged with high concentrations of H2O2 (> 110 MUM) whereas a slow and
      progressive loss of cultures was observed in more dilute (50-100 MUM) peroxide
      applications. In the latter case, the primary mode of cell death was apoptosis.
      These studies revealed that while rescue of H2O2 challenged cultures was achieved
      for necrotic cell death, no such sparing was observed in apoptotic cells. Based
      on the current and cumulative data regarding the membrane fusogenic properties of
      chitosan, we conclude that chitosan neuroprotection arises from its membrane
      sealing effects. Consistent with this hypothesis is the observation that
      apoptotic cells did not exhibit early stage membrane damage. These in vitro
      results elucidate mechanisms by which membrane fusogens may provide therapeutic
      benefit.

PMID- 29351806
TI  - Isolated septic arthritis of hip joint: a rare presentation of melioidosis. A
      case report.
AB  - BACKGROUND: Despite, Sri Lanka lies in the melioidosis endemic belt between 5
      degrees N and 10 degrees N surrounded by countries known to have endemic
      melioidosis for many years, comparatively fewer cases of melioidosis infection
      have been reported in Sri Lanka. Melioidosis has a wide spectrum of clinical
      presentation, ranging from severe pneumonia to abscess formation in various
      organs. Isolated septic arthritis, which is a rare but well-recognized
      manifestation of melioidosis, could be the sole presenting problem in some
      patients with melioidosis. CASE PRESENTATION: We report a middle aged diabetic
      female who has been on azathioprine for autoimmune hepatitis, presenting with
      pain and swelling of left hip joint. Investigations confirmed the clinical
      suspicion of septic arthritis, but all relevant microbiological investigations
      failed to isolate a causative organism. Due to the history of diabetes, possible
      immunosuppression with azathioprine, and failure to recognise the possible
      causative organism by initial investigations prompted us to investigate for
      melioidosis. Diagnosis of melioidosis was made by presence high titre of
      antibodies to melioidin antigen, and rapid response to appropriate treatment. The
      patient was treated with intravenous imipenem 1000 mg 6 hourly and oral
      cotrimoxazole (1920 mg 12 hourly) for 4 weeks followed by eradication therapy
      with cotrimoxazole and doxycycline. CONCLUSION: Given that melioidosis-induced
      septic arthritis share common features with septic arthritis due to other common
      pyogenic bacteria, differentiation of these two conditions is extremely
      difficult. Therefore, melioidosis needs to be considered as a possibility, when a
      patient with risk factors for melioidosis such as diabetes or immunosuppression
      presents with isolated septic arthritis. This case report has been presented to
      raise the awareness of an unusual presentation of melioidosis; isolated septic
      arthritis.

PMID- 29351807
TI  - Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men
      exposed to anabolic androgenic steroids.
AB  - OBJECTIVE: The primary aim of this study was to investigate the association
      between the vitamin D receptor polymorphisms rs2228570 (Fok1) and rs731236 (TaqI)
      and LH and FSH levels in relation to anabolic androgenic steroid (AAS) use.
      RESULTS: Two cohorts were analyzed. Cohort 1 comprised healthy volunteers given
      single supra-physiological doses of 500 mg testosterone (n = 25). Cohort 2
      comprised 45 self-reporting AAS users. Healthy volunteers homozygous for the C
      allele of the Fok1 polymorphism exhibited 30% higher LH levels than T-carriers at
      baseline (p = 0.04) and twice the levels 14 days after testosterone
      administration (p = 0.01). AAS users homozygous for the C-allele had four times
      higher LH levels than TT-individuals (p < 0.05). FSH levels were not associated
      with Fok1 polymorphism, nor were LH and FSH levels associated with the TaqI
      polymorphism. In conclusion, there is an association between LH levels and the
      Fok1 VDR polymorphism and this difference is even more pronounced in AAS users
      and subjects with suppressed LH levels.

PMID- 29351808
TI  - Clinicopathologic features of colorectal carcinoma: features predicting higher T
      stage and nodal metastasis.
AB  - OBJECTIVES: A rising frequency of colorectal carcinoma has been noted in recent
      years in Pakistan. In the present study, we aimed to evaluate clinicopathologic
      features of colorectal carcinoma in our population so that protocols could be
      developed to stratify patients that may require further biomarker/molecular
      testing. Furthermore, histological features which predict higher T and N stage
      were also evaluated. RESULTS: Median age at diagnosis was 54.5 (19-85) years. 79%
      cases were of conventional adenocarcinoma while 13% cases were of mucinous
      carcinoma. Most of the cases were at T3 stage (81%), while 27 and 68% of cases
      revealed lymphovascular invasion and nodal metastasis respectively. Mucinous and
      signet ring tumors were associated with a higher N stage. Pre-existing polyp was
      associated with lower T and N stage. We found a high proportion of our cases to
      present at advanced T-stage. Tumor grade and lymphovascular invasion were found
      to be associated with higher N-stage while tumor infiltrating lymphocytes was
      associated with lower T and N-stage. Moreover, a high frequency of mucinous
      differentiation may be linked to microsatellite instability in our cases of
      colorectal carcinoma; therefore, we suggest that microsatellite instability
      testing in colorectal carcinoma should be evaluated in our setup.

PMID- 29351809
TI  - Axonal transport in a peripheral diabetic neuropathy model: sex-dimorphic
      features.
AB  - BACKGROUND: Disruption of axonal transport plays a pivotal role in diabetic
      neuropathy. A sex-dimorphism exists in the incidence and symptomatology of
      diabetic neuropathy; however, no studies so far have addressed sex differences in
      axonal motor proteins expression in early diabetes as well as the possible
      involvement of neuroactive steroids. Interestingly, recent data point to a role
      for mitochondria in the sexual dimorphism of neurodegenerative diseases.
      Mitochondria have a fundamental role in axonal transport by producing the motors'
      energy source, ATP. Moreover, neuroactive steroids can also regulate
      mitochondrial function. METHODS: Here, we investigated the impact of short-term
      diabetes in the peripheral nervous system of male and female rats on key motor
      proteins important for axonal transport, mitochondrial function, and neuroactive
      steroids levels. RESULTS: We show that short-term diabetes alters mRNA levels and
      axoplasm protein contents of kinesin family member KIF1A, KIF5B, KIF5A and Myosin
      Va in male but not in female rats. Similarly, the expression of peroxisome
      proliferator-activated receptor gamma co-activator-1alpha, a subunit of the
      respiratory chain complex IV, ATP levels and the key regulators of mitochondrial
      dynamics were affected in males but not in females. Concomitant analysis of
      neuroactive steroid levels in sciatic nerve showed an alteration of testosterone,
      dihydrotestosterone, and allopregnanolone in diabetic males, whereas no changes
      were observed in female rats. CONCLUSIONS: These findings suggest that sex
      specific decrease in neuroactive steroid levels in male diabetic animals may
      cause an alteration in their mitochondrial function that in turn might impact in
      axonal transport, contributing to the sex difference observed in diabetic
      neuropathy.

PMID- 29351810
TI  - Identify Down syndrome transcriptome associations using integrative analysis of
      microarray database and correlation-interaction network.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) have previously been emerged as key
      players in a series of biological processes. Dysregulation of lncRNA is
      correlated to human diseases including neurological disorders. Here, we developed
      a multi-step bioinformatics analysis to study the functions of a particular Down
      syndrome-associated gene DSCR9 including the lncRNAs. The method is named
      correlation-interaction-network (COIN), based on which a pipeline is implemented.
      Co-expression gene network analysis and biological network analysis results are
      presented. METHODS: We identified the regulation function of DSCR9, a lncRNA
      transcribed from the Down syndrome critical region (DSCR) of chromosome 21, by
      analyzing its co-expression genes from over 1700 sets and nearly 60,000 public
      Affymetrix human U133-Plus 2 transcriptional profiling microarrays. After proper
      evaluations, a threshold is chosen to filter the data and get satisfactory
      results. Microarray data resource is from EBI database and protein-protein
      interaction (PPI) network information is incorporated from the most complete
      network databases. PPI integration strategy guarantees complete information
      regarding DSCR9. Enrichment analysis is performed to identify significantly
      correlated pathways. RESULTS: We found that the most significant pathways
      associated with the top DSCR9 co-expressed genes were shown to be involved in
      neuro-active ligand-receptor interaction (GLP1R, HTR4, P2RX2, UCN3, and UTS2R),
      calcium signaling pathway (CACNA1F, CACNG4, HTR4, P2RX2, and SLC8A3), neuronal
      system (KCNJ5 and SYN1) by the KEGG, and GO analysis. The A549 and U251 cell
      lines with stable DSCR9 overexpression were constructed. We validated 10 DSCR9 co
      expression genes by qPCR in both cell lines with over 70% accuracy. CONCLUSIONS:
      DSCR9 was highly correlated with genes that were known as important factors in
      the developments and functions of nervous system, indicating that DSCR9 may
      regulate neurological proteins regarding Down syndrome and other neurological
      related diseases. The pipeline can be properly adjusted to other applications.

PMID- 29351811
TI  - Rate and determinants of non-adherence to a gluten-free diet and nutritional
      status assessment in children and adolescents with celiac disease in a tertiary
      Brazilian referral center: a cross-sectional and retrospective study.
AB  - BACKGROUND: Compliance with a gluten-free diet (GFD) is difficult at all ages but
      particularly for teenagers due to social, cultural, economic, and practical
      pressures. The multidisciplinary team responsible for the treatment of patients
      with celiac disease and give support to their parents plays a special role on
      strengthening GFD and assessing the nutritional and physical health. METHODS: A
      cross-sectional and retrospective study including patients under 20 years of age,
      with biopsy-confirmed CD, followed regularly at the Department of Pediatrics,
      Division of Gastroenterology, Hospital das Clinicas, University of Sao Paulo,
      School of Medicine, Sao Paulo, Brazil, were surveyed using a questionnaire and
      serologic test applied between November 2011 and February 2012. A retrospective
      chart review of these patients was performed to collect the anthropometric data
      along with the results of the serologic test performed at the time of diagnosis
      and after at least 1 year of treatment with a GFD. RESULTS: We evaluated 35
      patients aged between 2.4 and 19.9 years. Of these 68.6% were female, 88.6% had
      the typical form of the disease and 51.4% had other comorbidities. The mean age
      at diagnosis was 5.4 years. Despite dietary guidance, 20% reported non-adherence
      to the diet. Most children recovered the weight and height deficit after 5 years
      of treatment, and in some children, excessive weight gain became a concern.
      CONCLUSION: The majority of transgressions occurred intentionally at home or at
      parties. There was a risk of excessive weight gain, especially in the first two
      years of treatment. More alternatives and easier access to low cost gluten-free
      foods, increasing the discussion about the benefits of adhering to a GFD among
      patients, families, and the general population, besides the acquisition of self
      management skills, are crucial to fostering independent children and adolescents
      who have the knowledge and tools to manage life with CD.

PMID- 29351812
TI  - A hybrid protein containing MSP1a repeats and Omp7, Omp8 and Omp9 epitopes
      protect immunized BALB/c mice against anaplasmosis.
AB  - Anaplasma marginale (A. marginale) has a remarkable impact on livestock
      production, and an effective vaccine is not currently available due to the
      inexistence of a small animal model. Recently, BALB/c mice were successfully
      infected with A. marginale, resulting in an acute and persistent anaplasmosis
      infection. Here, we designed a hybrid protein containing repeats of polypeptide
      1a from major surface protein-1 complex (MSP1a) repeats and common epitopes of
      outer membrane proteins (OMPs) OMP7, OMP8 and OMP9 expressed in Escherichia coli.
      Our proof-of-concept assessed vaccinal effectiveness against a challenge with
      live bacteria. The MSP1a/OMP7/8/9 immunized BALB/C mice exhibited a strong
      reduction in rickettsemia and had no signs of anaplasmosis or hepatic lesions. In
      contrast, the non-immunized mice exhibited signs of anaplasmosis and a body
      weight loss associated with increases in monocyte and neutrophil counts.
      Furthermore, the non-immunized mice displayed atrophies with chronic inflammatory
      infiltrates in the spleen and increased binucleation and hydropic degeneration in
      the hepatocytes. Our findings demonstrated that immunization with our hybrid
      protein induced a strong reduction in rickettsemia and conferred protection
      against anaplasmosis. Therefore, given the strong evidence of the protective
      effect against anaplasmosis, hybrid protein designs are potential candidates for
      the rational design of vaccinal subunits.

PMID- 29351813
TI  - Integrated biogeography of planktonic and sedimentary bacterial communities in
      the Yangtze River.
AB  - BACKGROUND: Bacterial communities are essential to the biogeochemical cycle in
      riverine ecosystems. However, little is presently known about the integrated
      biogeography of planktonic and sedimentary bacterial communities in large rivers.
      RESULTS: This study provides the first spatiotemporal pattern of bacterial
      communities in the Yangtze River, the largest river in Asia with a catchment area
      of 1,800,000 km2. We find that sedimentary bacteria made larger contributions
      than planktonic bacteria to the bacterial diversity of the Yangzte River
      ecosystem with the sediment subgroup providing 98.8% of 38,906 operational
      taxonomic units (OTUs) observed in 280 samples of synchronous flowing water and
      sediment at 50 national monitoring stations covering a 4300 km reach. OTUs within
      the same phylum displayed uniform seasonal variations, and many phyla
      demonstrated autumn preference throughout the length of the river. Seasonal
      differences in bacterial communities were statistically significant in water,
      whereas bacterial communities in both water and sediment were geographically
      clustered according to five types of landforms: mountain, foothill, basin,
      foothill-mountain, and plain. Interestingly, the presence of two huge dams
      resulted in a drastic fall of bacterial taxa in sediment immediately downstream
      due to severe riverbed scouring. The integrity of the biogeography is
      satisfactorily interpreted by the combination of neutral and species sorting
      perspectives in meta-community theory for bacterial communities in flowing water
      and sediment. CONCLUSIONS: Our study fills a gap in understanding of bacterial
      communities in one of the world's largest river and highlights the importance of
      both planktonic and sedimentary communities to the integrity of bacterial
      biogeographic patterns in a river subject to varying natural and anthropogenic
      impacts.

PMID- 29351814
TI  - SETDB1 prevents TET2-dependent activation of IAP retroelements in naive embryonic
      stem cells.
AB  - BACKGROUND: Endogenous retroviruses (ERVs), which are responsible for 10% of
      spontaneous mouse mutations, are kept under control via several epigenetic
      mechanisms. The H3K9 histone methyltransferase SETDB1 is essential for ERV
      repression in embryonic stem cells (ESCs), with DNA methylation also playing an
      important role. It has been suggested that SETDB1 protects ERVs from TET
      dependent DNA demethylation, but the relevance of this mechanism for ERV
      expression remains unclear. Moreover, previous studies have been performed in
      primed ESCs, which are not epigenetically or transcriptionally representative of
      preimplantation embryos. RESULTS: We use naive ESCs to investigate the role of
      SETDB1 in ERV regulation and its relationship with TET-mediated DNA
      demethylation. Naive ESCs show an increased dependency on SETDB1 for ERV
      silencing when compared to primed ESCs, including at the highly mutagenic
      intracisternal A particles (IAPs). We find that in the absence of SETDB1, TET2
      activates IAP elements in a catalytic-dependent manner. Surprisingly, TET2 does
      not drive changes in DNA methylation levels at IAPs, suggesting that it regulates
      these retrotransposons indirectly. Instead, SETDB1 depletion leads to a TET2
      dependent loss of H4R3me2s, which is indispensable for IAP silencing during
      epigenetic reprogramming. CONCLUSIONS: Our results demonstrate a novel and
      unexpected role for SETDB1 in protecting IAPs from TET2-dependent histone
      arginine demethylation.

PMID- 29351815
TI  - Ready-to-use protein G-conjugated gold nanorods for biosensing and biomedical
      applications.
AB  - BACKGROUND: Gold nanorods (GNRs) display unique capacity to absorb and scatter
      near infrared light, which arises from their peculiar composition of surface
      plasmon resonances. For this reason, GNRs have become an innovative material of
      great hope in nanomedicine, in particular for imaging and therapy of cancer, as
      well as in photonic sensing of biological agents and toxic compounds for e.g.
      biomedical diagnostics, forensic analysis and environmental monitoring. As the
      use of GNRs is becoming more and more popular, in all these contexts, there is
      emerging a latent need for simple and versatile protocols for their modification
      with targeting units that may convey high specificity for any analyte of interest
      of an end-user. RESULTS: We introduce protein G-coated GNRs as a versatile
      solution for the oriented immobilization of antibodies in a single step of
      mixing. We assess this strategy against more standard covalent binding of
      antibodies, in terms of biocompatibility and efficiency of molecular recognition
      in buffer, serum and plasma, in the context of the development of a direct
      immunoenzymatic assay. In both cases, we estimate an average of around 30 events
      of molecular recognition per particle. In addition, we disclose a convenient
      protocol to store these particles for months in a freezer, without any
      detrimental effect. CONCLUSIONS: The biocompatibility and efficiency of molecular
      recognition is similar in either case of GNRs that are modified with antibodies
      by covalent binding or oriented immobilization through protein G. However,
      protein G-coated GNRs are most attractive for an end-user, owing to their unique
      versatility and ease of bioconjugation with antibodies of her/his choice.

PMID- 29351817
TI  - Standard Method Performance Requirements (SMPRs(r)) and Corresponding AOAC First
      and Final Action Official MethodsSM.

PMID- 29351816
TI  - Effects of gut-derived endotoxin on anxiety-like and repetitive behaviors in male
      and female mice.
AB  - BACKGROUND: Gut dysbiosis is observed in several neuropsychiatric disorders
      exhibiting increases in anxiety behavior, and recent work suggests links between
      gut inflammation and such disorders. One source of this inflammation may be
      lipopolysaccharide (LPS), a toxic component of gram-negative bacteria. Here, we
      (1) determine whether oral gavage of LPS, as a model of gut-derived endotoxemia,
      affects anxiety-like and/or repetitive behaviors; (2) test whether these changes
      depend on TLR4 signaling; and (3) test the extent to which gut-derived endotoxin
      and TLR4 antagonism affects males and females differently. METHODS: In experiment
      1, male wild-type (WT) and Tlr4-/- mice were tested for locomotor, anxiety-like,
      and repetitive behaviors in an automated open field test apparatus, 2 h after
      oral gavage of LPS or saline. In experiment 2, male and female WT mice received
      an oral gavage of LPS and an injection of one or two TLR4 antagonists that target
      different TLR4 signaling pathways ((+)-naloxone and LPS derived from R.
      sphaeroides (LPS-RS)). Univariate and multivariate analyses were used to identify
      effects of treatment, sex, and genotype and their interaction. RESULTS: In
      experiment 1, oral gavage of LPS increased anxiety-like behavior in male WT mice
      but not in Tlr4-/- mice. In experiment 2, oral gavage of LPS increased anxiety
      like and decreased repetitive behaviors in WT mice of both sexes. Neither
      antagonist directly blocked the effects of orally administered LPS. However,
      treatment with (+)-naloxone, which blocks the TRIF pathway of TLR4, had opposing
      behavioral effects in males and females (independent of LPS treatment). We also
      identified sex differences in the expression of interleukin-6, a pro-inflammatory
      cytokine, in the gut both in basal conditions and in response to LPS. CONCLUSION:
      In spite of the ubiquitous nature of LPS in the gut lumen, this is the first
      study to demonstrate that intestinally derived LPS can initiate behavioral
      aspects of the sickness response. While an increased enteric load of LPS
      increases anxiety-like behavior in both sexes, it likely does so via sex-specific
      mechanisms. Similarly, TLR4 signaling may promote baseline expression of
      repetitive behavior differently in males and females. This study lays the
      groundwork for future interrogations into connections between gut-derived
      endotoxin and behavioral pathology in males and females.

PMID- 29351818
TI  - Obstructive Sleep Apnea in Patients With Congenital Central Hypoventilation
      Syndrome Ventilated by Diaphragm Pacing Without Tracheostomy.
AB  - STUDY OBJECTIVES: To determine presence of obstructive sleep apnea (OSA) in
      patients with congenital central hypoventilation syndrome (CCHS) ventilated by
      diaphragm pacing (DP) without tracheostomy, and to determine if OSA can be
      improved by DP setting changes. METHODS: We reviewed polysomnography (PSG)
      results of 15 patients with CCHS from October 2001 to April 2014, age 15.4 +/-
      7.8 years, body mass index 22.0 +/- 6.0 kg/m2, and 60% female. RESULTS: Of the 22
      PSG results obtained for the 15 patients with CCHS, 9 were performed with
      tracheostomy capped, and 13 were performed after patients underwent
      decannulation. OSA was present on 6 of 9 tests in patients with tracheostomy
      capped, including 3 patients with immediate, severe OSA necessitating that the
      studies be completed with tracheostomy uncapped. OSA was present on 2 of 13 tests
      in patients in whom decannulation had been performed. Hypoventilation was seen on
      only one test without OSA. On 2 of 5 tests showing OSA, OSA improved by
      decreasing DP amplitude settings; apnea-hypopnea index decreased from 11.1 +/-
      2.5 to 1.8 +/- 2.5 events/h; PETCO2 decreased from 57.5 +/- 3.5 to 38.5 +/- 0.7
      torr; SpO2 increased from 76.5 +/- 0.7% to 93.0 +/- 7.1%. OSA improved in one
      patient with slight increase in respiratory rate. Settings were manipulated in 4
      tests showing OSA; no changes were attempted in the remaining study. One patient
      was placed on bilevel positive airway pressure with temporary suspension of DP.
      Age (P < .119), previous adenotonsillectomy (P < .211), and body mass index (P <
      .112) did not significantly contribute to OSA. CONCLUSIONS: OSA occurs in
      patients with CCHS ventilated by DP. However, decreasing DP amplitude settings
      can lessen upper airway obstruction without compromising gas exchange.

PMID- 29351819
TI  - Patient-Reported Outcomes in Older Adults With Obstructive Sleep Apnea Treated
      With Continuous Positive Airway Pressure Therapy.
AB  - STUDY OBJECTIVES: Although continuous positive airway pressure (CPAP) therapy is
      regarded as the gold standard treatment for obstructive sleep apnea (OSA) in
      adults, outcomes in older patients are limited. This study examines the effect of
      CPAP therapy in older adults with OSA (older than 60 years) compared to younger
      adults (age 18 to 60 years) to inform the current standard of practice. METHODS:
      We performed a retrospective study with a convenience sample to compare responses
      to CPAP treatment in older versus younger adults with OSA using validated,
      patient-reported outcomes (PROs). A total of 532 patients were analyzed at
      baseline and at 3, 6, and 12 months after CPAP initiation. The effects of CPAP
      adherence and OSA severity on PRO scores were measured in each age group.
      RESULTS: Patients older than 60 years had higher apnea-hypopnea indices but lower
      Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), and Patient Health
      Questionnaire-9 (PHQ-9) scores and higher Functional Outcomes of Sleep
      Questionnaire (FOSQ) scores at baseline compared to patients age 18 to 60 years.
      At 1 year after CPAP initiation, significant and comparable improvements in ESS,
      FSS, PHQ-9, and FOSQ scores were observed in patients older than 60 years
      relative to younger patients. When stratifying by OSA severity, change between
      age groups was significantly different only for PHQ-9 in patients with mild OSA,
      with greater improvements observed in younger patients. CONCLUSIONS: This study
      adds to the limited data on treatment outcomes with CPAP therapy in older adults
      with OSA. Patients older than 60 years achieve improvement in sleepiness,
      fatigue, depressive symptoms, and quality of life analogous to that of younger
      adults.

PMID- 29351820
TI  - Restless Legs Syndrome in Iranian People With Type 2 Diabetes Mellitus: The Role
      in Quality of Life and Quality of Sleep.
AB  - STUDY OBJECTIVES: To investigate the prevalence of restless legs syndrome (RLS)
      in patients with type 2 diabetes mellitus (T2DM) and explore its role in quality
      of life (QoL) and quality of sleep of these patients. METHODS: This is a cross
      sectional study performed on 210 Iranian people with T2DM. The diagnosis of RLS
      was established based on the essential diagnostic criteria for RLS recommended by
      the National Institutes of Health. Sleep quality and QoL were assessed in all
      participants using Pittsburgh Sleep Quality Index and EuroQol five-dimension
      questionnaire, respectively. Regression models were used for final analysis of
      data. RESULTS: The prevalence of RLS was 19.5%; of whom 38.1% had poor quality of
      sleep. Male sex, being single, body mass index (BMI), and RLS were associated
      with poor quality of sleep. Patients with RLS were almost three times as likely
      as the patients without RLS to have poor sleep quality. Moreover, being female,
      BMI value, level of glycosylated hemoglobine (HbA1C), and RLS were associated
      with lower QoL. RLS lowers the score of QoL even more than BMI and HbA1C. In
      addition, the QoL and sleep quality of this population of patients with diabetes
      have not been affected by the severity of RLS as well as presence or absence of
      neuropathy. CONCLUSIONS: RLS has an independent and significant role in sleep
      quality and QoL in the patients with diabetes. Neuropathy with RLS does not
      confer any additive burden on QoL and sleep quality of this population of
      patients with diabetes.

PMID- 29351821
TI  - Reliability of the American Academy of Sleep Medicine Rules for Assessing Sleep
      Depth in Clinical Practice.
AB  - STUDY OBJECTIVES: The American Academy of Sleep Medicine has published manuals
      for scoring polysomnograms that recommend time spent in non-rapid eye movement
      sleep stages (stage N1, N2, and N3 sleep) be reported. Given the well-established
      large interrater variability in scoring stage N1 and N3 sleep, we determined the
      range of time in stage N1 and N3 sleep scored by a large number of technologists
      when compared to reasonably estimated true values. METHODS: Polysomnograms of 70
      females were scored by 10 highly trained sleep technologists, two each from five
      different academic sleep laboratories. Range and confidence interval (CI =
      difference between the 5th and 95th percentiles) of the 10 times spent in stage
      N1 and N3 sleep assigned in each polysomnogram were determined. Average values of
      times spent in stage N1 and N3 sleep generated by the 10 technologists in each
      polysomnogram were considered representative of the true values for the
      individual polysomnogram. Accuracy of different technologists in estimating delta
      wave duration was determined by comparing their scores to digitally determined
      durations. RESULTS: The CI range of the ten N1 scores was 4 to 39 percent of
      total sleep time (% TST) in different polysomnograms (mean CI +/- standard
      deviation = 11.1 +/- 7.1 % TST). Corresponding range for N3 was 1 to 28 % TST
      (14.4 +/- 6.1 % TST). For stage N1 and N3 sleep, very low or very high values
      were reported for virtually all polysomnograms by different technologists.
      Technologists varied widely in their assignment of stage N3 sleep, scoring that
      stage when the digitally determined time of delta waves ranged from 3 to 17
      seconds. CONCLUSIONS: Manual scoring of non-rapid eye movement sleep stages is
      highly unreliable among highly trained, experienced technologists. Measures of
      sleep continuity and depth that are reliable and clinically relevant should be a
      focus of clinical research.

PMID- 29351822
TI  - Influence of Obstructive Sleep Apnea in the Functional Aspects of Patients With
      Osteoarthritis.
AB  - STUDY OBJECTIVES: It has been demonstrated in recent studies that obstructive
      sleep apnea (OSA) is the most prevalent sleep disorder in patients with
      osteoarthritis (OA), and thus the current study aimed to investigate the
      influence of OSA on knee extensor torque, pain, stiffness, and physical function
      in men with low-grade knee OA. METHODS: The study included 60 male volunteers,
      aged 40 to 70 years, allocated into four groups: Group 1 (G1) Control (n = 15):
      without OA and without OSA; Group 2 (G2) (n = 15): with OA and without OSA; Group
      3 (G3) (n = 15): without OA and with OSA; and Group 4 (G4) (n = 15) with OA and
      with OSA. All volunteers were examined using knee radiographs and
      polysomnography, responded to the Western Ontario McMaster Osteoarthritis Index
      (WOMAC) questionnaire, and completed a test on an isokinetic dynamometer to
      evaluate peak isometric knee extensor torque, both concentric and eccentric (90
      degrees /s and 180 degrees /s). RESULTS: Regarding the data from the WOMAC
      questionnaire (for pain, stiffness, and physical function), it was observed that
      G4 showed higher values compared to G1 or G3. For the concentric isometric and
      isokinetic peak knee extensor torque, lower values were observed in G4 compared
      to G1 or G3. CONCLUSIONS: Patients who have knee OA in the early grades, when
      associated with OSA, have higher changes of the peak extensor torque, pain,
      stiffness, and physical function, compared with patients who did not have OSA.
      CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Identifier:
      NCT01422967, Title: Changes Of Sleep on the Sensoriomotor and Cytokine In
      Patients With Osteoarthritis, URL:
      https://clinicaltrials.gov/ct2/show/NCT01422967.

PMID- 29351824
TI  - Nurse Practitioners and Physician Assistants Are Important to the Sleep Team.

PMID- 29351823
TI  - Nurse Practitioners and Physician Assistants Are Qualified to Perform Home Sleep
      Apnea Test Clinical Evaluations.

PMID- 29351825
TI  - CPAP Adherence and Readmission: Marker of Health or Cost-Effective Tool?

PMID- 29351826
TI  - Nonadherence to CPAP Associated With Increased 30-Day Hospital Readmissions.
AB  - STUDY OBJECTIVES: The primary objective of this study was to determine if
      nonadherence to continuous positive airway pressure (CPAP) is associated with
      increased 30-day all-cause, cardiovascular-cause, and pulmonary-cause hospital
      readmissions. METHODS: Retrospective cohort study at a Veterans Affairs hospital
      of patients with obstructive sleep apnea (OSA) who were hospitalized from January
      1, 2007 to December 31, 2015. Odds ratio of 30-day readmission was calculated for
      all-cause, cardiovascular-cause, and pulmonary-cause readmissions. Logistic
      regression model was used to evaluate odds of nonadherent versus adherent group
      while adjusting for age, sex, body mass index, living situation, race,
      comorbidities, and medication adherence. RESULTS: Out of 2,077 records reviewed,
      345 patients (183 adherent and 162 nonadherent) met our inclusion criteria. The
      adherent group had a total of 215 initial admissions, and the nonadherent group
      had a total of 268 index admissions. Thirty-day all-cause readmission rate was
      significantly higher in the nonadherent group, with an adjusted odds ratio (OR)
      of 3.52 (95% confidence interval [CI], 2.04-6.08, P < .001). Thirty-day
      cardiovascular-cause readmission rate was significantly higher in the nonadherent
      group, with an adjusted OR of 2.31 (95% CI, 1.11-4.78, P = .024). Difference in
      30-day pulmonary-cause readmissions was not statistically significant, with an
      adjusted OR of 3.66 (95% CI, 0.41-32.76, P = .25). CONCLUSIONS: Nonadherence to
      CPAP is associated with increased 30-day all-cause and cardiovascular-cause
      readmission in patients with OSA. Ensuring CPAP adherence is crucial in
      addressing general and cardiovascular-related healthcare utilization and
      morbidity in patients with OSA. COMMENTARY: A commentary on this article appears
      in this issue on page 161.

PMID- 29351828
TI  - Activity During Sleep Measured by a Sheet-Shaped Body Vibrometer and the Severity
      of Atopic Dermatitis in Adults: A Comparison With Wrist Actigraphy.
AB  - STUDY OBJECTIVES: To use a sheet-shaped body vibrometer (SBV) for measuring sleep
      in adult patients with atopic dermatitis (AD) of various severities and to
      compare the results with those measured by wrist actigraphy (WA). METHODS:
      Simultaneous measurements of activity during sleep by WA and the SBV were
      performed in 20 outpatients with AD for 5 to 10 days. The mean activity count per
      minute (ACT) and sleep efficiency (SE) were obtained using each device. The
      severity of AD was evaluated by the severity scoring of AD (SCORAD), serum thymus
      and activation-regulated chemokine (TARC) level, serum total immunoglobulin E
      level, and peripheral eosinophil count. RESULTS: The ACT measured by WA was
      correlated with SCORAD (Spearman correlation coefficient [rs] = .64, P = .002)
      and TARC (rs = .60, P = .005). The ACT obtained by the SBV was significantly
      correlated with TARC (rs = .58, P = .008) and ACT obtained by WA (rs = .63, P =
      .003). SE obtained by WA resulted in lower values compared with SE obtained by
      the SBV (69.7 +/- 9.4% versus 82.9 +/- 9.3%, P < .001), although SE obtained by
      WA was highly correlated with SE obtained by the SBV (rs = .82, P < .001). Bland
      Altman plots revealed that SE measured by WA always had lower values in all the
      patients. CONCLUSIONS: Activity during sleep, presumably composed of scratching
      and other motions, is more vigorous in patients with severe adult AD. This was
      successfully demonstrated by the SBV and WA assessment. However, we consider that
      ACT measured by WA is more suited for the scratch evaluation and SE measured by
      the SBV is preferable for the sleep evaluation.

PMID- 29351827
TI  - Nocturnal REM Sleep Without Atonia Is a Diagnostic Biomarker of Pediatric
      Narcolepsy.
AB  - STUDY OBJECTIVES: Compare nocturnal REM sleep without atonia (nRWA) and REM sleep
      behavior disorder (RBD) between pediatric patients with and without narcolepsy
      and determine if the nRWA index is a valid diagnostic biomarker for narcolepsy.
      METHODS: Retrospective cohort study of children ages 6 to 18 years who completed
      a nocturnal polysomnogram (PSG) and Multiple Sleep Latency Test (MSLT). Our study
      sample included 11 patients with narcolepsy type 1 (NT1), 6 with narcolepsy type
      2 (NT2), 12 with idiopathic hypersomnia (IH), and 11 with subjective hypersomnia
      (sHS). We compared group nRWA indices (epochs of RWA/total stage R sleep epochs)
      from the nocturnal PSGs and analyzed nRWA index receiver operating curve (ROC)
      statistics for narcolepsy diagnosis. RESULTS: The median nRWA index of patients
      with NT1 was 15 to 30 times higher compared to sHS and IH (Ps < .005) but similar
      to that of the NT2 group (P = .46). RBD was present in 25% of patients with
      narcolepsy (NT1 and NT2). In comparing those with and without narcolepsy, the
      nRWA index area under the curve was 0.87 (0.6), 95% confidence interval (CI) =
      0.75 to 0.99, P < .001. The threshold of having >= 1% of stage R sleep epochs
      with nRWA yielded a sensitivity of 88.2%, 95% CI = 63.6-98.5 and specificity of
      60.9%, 95% CI = 38.5 to 80.3 for diagnosis of narcolepsy. In contrast, a
      threshold of >= 8% yielded a specificity of 95.7%, 95% CI = 78.1 to 99.9 and
      sensitivity of 52.9%, 95% CI = 27.8 to 77. CONCLUSIONS: The nRWA index is a very
      good diagnostic biomarker of pediatric narcolepsy. Depending on the clinical
      cutoffs utilized, this biomarker can identify more children/adolescents with
      narcolepsy using just the PSG or reduce false-positive diagnostic results.

PMID- 29351829
TI  - Inhibition of dynamin-related protein 1 has neuroprotective effect comparable
      with therapeutic hypothermia in a rat model of cardiac arrest.
AB  - Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, it has been
      proven that inhibition of Drp1 by mdivi-1 improves survival and attenuates
      cerebral ischemic injury after cardiac arrest. In this study, we compared the
      effects of Drp1 inhibition with therapeutic hypothermia on post-resuscitation
      neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4
      groups: mdivi-1 treatment group (n = 39), hypothermic group (n = 38),
      normothermic group (n = 41), and sham group (n = 12). The rats in the mdivi-1
      treatment group were received intravenously 1.2 mg/kg of mdivi-1 at 1 minute
      after the return of spontaneous circulation (ROSC). In rats in hypothermia group,
      rapid cooling was initiated at 5 minutes after resuscitation, and the core
      temperature was maintained to 33 +/- 0.5 degrees C for 2 hours. The results
      showed that both Drp1 inhibition and therapeutic hypothermia increased 3-day
      survival time (all P <0.05) and improved neurologic function up to 72 hours post
      cardiac arrest. In addition, both Drp1 inhibition and therapeutic hypothermia
      decreased cell injury, apoptosis in hippocampal cornu ammonis 1 region and brain
      mitochondrial dysfunction including adenosine triphosphate production, reactive
      oxygen species and mitochondrial membrane potential after cardiac arrest.
      Moreover, therapeutic hypothermia decreased mitochondrial Drp1 expression and
      mitochondrial fission after cardiac arrest. In conclusion, inhibition of Drp1 has
      a similar effect to therapeutic hypothermia on neurologic outcome after
      resuscitation in this cardiac arrest rat model, and the neuroprotective effects
      of therapeutic hypothermia are associated with inhibition of mitochondrial
      fission.

PMID- 29351830
TI  - Anticoagulation for Portal Vein Thrombosis in Cirrhosis: Selection of Appropriate
      Patients.

PMID- 29351831
TI  - An Unexpected Cause of Recurrent Melena.

PMID- 29351832
TI  - Reply.

PMID- 29351833
TI  - Hepatic Mass in a Patient With Bladder Cancer History.

PMID- 29351834
TI  - Reply.

PMID- 29351835
TI  - Anticoagulation for Portal Vein Thrombosis in Liver Cirrhosis: Not Only
      Recanalize the Portal Vein.

PMID- 29351836
TI  - Interrogating Interactions and Modifications of Histones in Live Cells.
AB  - In this issue of Cell Chemical Biology, new methods are reported to interrogate
      histone interactions and modifications. Kleiner et al. (2018) develop a chemical
      proteomics platform for profiling of direct, context-dependent histone-protein
      interactions in living cells, and Delachat et al. (2018) engineer fluorescent
      sensors for coexisting histone modifications in live stem cells.

PMID- 29351837
TI  - Try Me: Promiscuous Inhibitors Still Allow for Selective Targeted Protein
      Degradation.
AB  - In this issue of Cell Chemical Biology, Bondeson et al. (2018), Burslem et al.
      (2018), and Huang et al. (2018) systematically characterize proteolysis-targeting
      chimeras (PROTACs) regarding their specificity and general advantages of targeted
      proteolysis of cellular proteins and provide interesting insights into possible
      future developments.

PMID- 29351838
TI  - The mediating effect of coping style on personality and mental health among
      elderly Chinese empty-nester: A cross-sectional study.
AB  - BACKGROUND: Mental health is a growing concern among older people all over the
      world. China has a rapidly aging population, and the number of elderly empty
      nesters, who have no children or whose children have already left home, is on the
      rise. These older adults live alone or with a spouse. Therefore, we should be
      concerned about these empty-nester, especially their mental health, due to its
      vital role. METHODS: This cross-sectional study was performed from March to
      December 2015. The participants were 350 empty-nest elderly adults from Chifeng
      City in Inner Mongolia. Data were collected with the Elderly Mental Health
      Questionnaire, the Eysenck Personality Questionnaire-Revised Short Scale for
      Chinese (EPQ-RSC) and the Simplified Coping Style Questionnaire. For the
      analyses, correlations, regressions, and structural equation models were used.
      Bootstrapping was performed to confirm the mediation effect. RESULTS: The mean
      age of the study population was 70.33 +/- 6.67 years. Mental health showed
      significant correlations with extraversion, neuroticism, and coping style (all
      P<0.01). Extraversion, neuroticism, and psychoticism were the independent
      variables, while mental health was the dependent variable in the linear
      regression model with stepwise analysis. Extraversion and neuroticism were
      entered into the regression equation. All standardized coefficients (beta) were
      significant (all P<0.01) in the model, and bootstrapping indicated that the
      mediating role of coping style was statistically significant. CONCLUSION: Coping
      style partially mediated the relationship between the personality and mental
      health of the empty-nest elderly. Consequently, to improve the mental health of
      the empty-nest elderly, coping style should be the focus.

PMID- 29351839
TI  - Activating and Repressing IRE1alpha: The Hsp47 and BiP Tug of War.
AB  - In this issue of Molecular Cell, Sepulveda et al. (2018) discovered an
      interesting role of Hsp47 in regulating the unfolded protein response (UPR)
      wherein Hsp47 binds to IRE1alpha and displaces BiP, thereby activating the
      IRE1alpha arm of the UPR pathway by a previously undetermined mechanism.

PMID- 29351840
TI  - Membrane Protein Dislocation by the Rhomboid Pseudoprotease Dfm1: No Pore Needed?
AB  - Defective ER-resident membrane proteins need to be ejected into the cytoplasm in
      order to be degraded by the proteasome, but the exact mechanism remains unclear.
      In this issue of Molecular Cell, Neal et al. (2018) reveal that the rhomboid
      pseudoprotease Dfm1 defines the central ERAD component for membrane protein
      dislocation.

PMID- 29351841
TI  - No Excess Baggage: New Life Starts with a Clean Slate.
AB  - A new mechanism for clearing protein damage from maturing oocytes has been
      described in a recent study by Bohnert and Kenyon (2017), who demonstrated that
      sperm-secreted hormones activate a vascular H+-ATPase pump that acidifies
      lysosomes and thus restores protein homeostasis.

PMID- 29351843
TI  - Cellular Handling of Protein Aggregates by Disaggregation Machines.
AB  - Both acute proteotoxic stresses that unfold proteins and expression of disease
      causing mutant proteins that expose aggregation-prone regions can promote protein
      aggregation. Protein aggregates can interfere with cellular processes and deplete
      factors crucial for protein homeostasis. To cope with these challenges, cells are
      equipped with diverse folding and degradation activities to rescue or eliminate
      aggregated proteins. Here, we review the different chaperone disaggregation
      machines and their mechanisms of action. In all these machines, the coating of
      protein aggregates by Hsp70 chaperones represents the conserved, initializing
      step. In bacteria, fungi, and plants, Hsp70 recruits and activates Hsp100
      disaggregases to extract aggregated proteins. In the cytosol of metazoa, Hsp70 is
      empowered by a specific cast of J-protein and Hsp110 co-chaperones allowing for
      standalone disaggregation activity. Both types of disaggregation machines are
      supported by small Hsps that sequester misfolded proteins.

PMID- 29351842
TI  - Maintaining a Healthy Proteome during Oxidative Stress.
AB  - Some of the most challenging stress conditions that organisms encounter during
      their lifetime involve the transient accumulation of reactive oxygen and chlorine
      species. Extremely reactive to amino acid side chains, these oxidants cause
      widespread protein unfolding and aggregation. It is therefore not surprising that
      cells draw on a variety of different strategies to counteract the damage and
      maintain a healthy proteome. Orchestrated largely by direct changes in the thiol
      oxidation status of key proteins, the response strategies involve all layers of
      protein protection. Reprogramming of basic biological functions helps decrease
      nascent protein synthesis and restore redox homeostasis. Mobilization of
      oxidative stress-activated chaperones and production of stress-resistant non
      proteinaceous chaperones prevent irreversible protein aggregation. Finally, redox
      controlled increase in proteasome activity removes any irreversibly damaged
      proteins. Together, these systems pave the way to restore protein homeostasis and
      enable organisms to survive stress conditions that are inevitable when living an
      aerobic lifestyle.

PMID- 29351844
TI  - Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of
      the Unfolded Protein Response Transducer IRE1alpha.
AB  - Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic
      signaling network known as the unfolded protein response (UPR). IRE1alpha is a
      major UPR transducer, determining cell fate under ER stress. We used an
      interactome screening to unveil several regulators of the UPR, highlighting the
      ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated
      that Hsp47 instigates IRE1alpha signaling through a physical interaction. Hsp47
      directly binds to the ER luminal domain of IRE1alpha with high affinity,
      displacing the negative regulator BiP from the complex to facilitate IRE1alpha
      oligomerization. The regulation of IRE1alpha signaling by Hsp47 is evolutionarily
      conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency
      sensitized cells and animals to experimental ER stress, revealing the
      significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47
      adjusts IRE1alpha signaling by fine-tuning the threshold to engage an adaptive
      UPR.

PMID- 29351845
TI  - A Precise Cdk Activity Threshold Determines Passage through the Restriction
      Point.
AB  - At the restriction point (R), mammalian cells irreversibly commit to divide. R
      has been viewed as a point in G1 that is passed when growth factor signaling
      initiates a positive feedback loop of Cdk activity. However, recent studies have
      cast doubt on this model by claiming R occurs prior to positive feedback
      activation in G1 or even before completion of the previous cell cycle. Here we
      reconcile these results and show that whereas many commonly used cell lines do
      not exhibit a G1 R, primary fibroblasts have a G1 R that is defined by a precise
      Cdk activity threshold and the activation of cell-cycle-dependent transcription.
      A simple threshold model, based solely on Cdk activity, predicted with more than
      95% accuracy whether individual cells had passed R. That a single measurement
      accurately predicted cell fate shows that the state of complex regulatory
      networks can be assessed using a few critical protein activities.

PMID- 29351846
TI  - Dual Strategies for Argonaute2-Mediated Biogenesis of Erythroid miRNAs Underlie
      Conserved Requirements for Slicing in Mammals.
AB  - While Slicer activity of Argonaute is central to RNAi, conserved roles of slicing
      in endogenous regulatory biology are less clear, especially in mammals.
      Biogenesis of erythroid Dicer-independent mir-451 involves Ago2 catalysis, but
      mir-451-KO mice do not phenocopy Ago2 catalytic-dead (Ago2-CD) mice, suggesting
      other needs for slicing. Here, we reveal mir-486 as another dominant erythroid
      miRNA with atypical biogenesis. While it is Dicer dependent, it requires slicing
      to eliminate its star strand. Thus, in Ago2-CD conditions, miR-486-5p is
      functionally inactive due to duplex arrest. Genome-wide analyses reveal miR-486
      and miR-451 as the major slicing-dependent miRNAs in the hematopoietic system.
      Moreover, mir-486-KO mice exhibit erythroid defects, and double knockout of mir
      486/451 phenocopies the cell-autonomous effects of Ago2-CD in the hematopoietic
      system. Finally, we observe that Ago2 is the dominant-expressed Argonaute in
      maturing erythroblasts, reflecting a specialized environment for processing
      slicing-dependent miRNAs. Overall, the mammalian hematopoietic system has evolved
      multiple conserved requirements for Slicer-dependent miRNA biogenesis.

PMID- 29351848
TI  - A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination.
AB  - Erroneous DNA repair by heterologous recombination (Ht-REC) is a potential threat
      to genome stability, but evidence supporting its prevalence is lacking. Here we
      demonstrate that recombination is possible between heterologous sequences and
      that it is a source of chromosomal alterations in mitotic and meiotic cells.
      Mechanistically, we find that the RTEL1 and HIM-6/BLM helicases and the BRCA1
      homolog BRC-1 counteract Ht-REC in Caenorhabditis elegans, whereas mismatch
      repair does not. Instead, MSH-2/6 drives Ht-REC events in rtel-1 and brc-1
      mutants and excessive crossovers in rtel-1 mutant meioses. Loss of vertebrate
      Rtel1 also causes a variety of unusually large and complex structural variations,
      including chromothripsis, breakage-fusion-bridge events, and tandem duplications
      with distant intra-chromosomal insertions, whose structure are consistent with a
      role for RTEL1 in preventing Ht-REC during break-induced replication. Our data
      establish Ht-REC as an unappreciated source of genome instability that underpins
      a novel class of complex genome rearrangements that likely arise during
      replication stress.

PMID- 29351847
TI  - Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and
      Oncogenic Function.
AB  - Sustained energy starvation leads to activation of AMP-activated protein kinase
      (AMPK), which coordinates energy status with numerous cellular processes
      including metabolism, protein synthesis, and autophagy. Here, we report that AMPK
      phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the
      interaction between EZH2 and SUZ12, another core component of the polycomb
      repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of
      histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor
      suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed
      tumor cell growth both in cell culture and mouse xenografts. Pathologically,
      immunohistochemical analyses uncovered a positive correlation between AMPK
      activity and pT311-EZH2, and higher pT311-EZH2 correlates with better survival in
      both ovarian and breast cancer patients. Our finding suggests that AMPK agonists
      might be promising sensitizers for EZH2-targeting cancer therapies.

PMID- 29351850
TI  - Systematic Gene-to-Phenotype Arrays: A High-Throughput Technique for Molecular
      Phenotyping.
AB  - We have developed a highly parallel strategy, systematic gene-to-phenotype arrays
      (SGPAs), to comprehensively map the genetic landscape driving molecular
      phenotypes of interest. By this approach, a complete yeast genetic mutant array
      is crossed with fluorescent reporters and imaged on membranes at high density and
      contrast. Importantly, SGPA enables quantification of phenotypes that are not
      readily detectable in ordinary genetic analysis of cell fitness. We benchmark
      SGPA by examining two fundamental biological phenotypes: first, we explore
      glucose repression, in which SGPA identifies a requirement for the Mediator
      complex and a role for the CDK8/kinase module in regulating transcription.
      Second, we examine selective protein quality control, in which SGPA identifies
      most known quality control factors along with U34 tRNA modification, which acts
      independently of proteasomal degradation to limit misfolded protein production.
      Integration of SGPA with other fluorescent readouts will enable genetic
      dissection of a wide range of biological pathways and conditions.

PMID- 29351849
TI  - The Dfm1 Derlin Is Required for ERAD Retrotranslocation of Integral Membrane
      Proteins.
AB  - Endoplasmic reticulum (ER)-associated degradation (ERAD) removes misfolded
      proteins from the ER membrane and lumen by the ubiquitin-proteasome pathway.
      Retrotranslocation of ubiquitinated substrates to the cytosol is a universal
      feature of ERAD that requires the Cdc48 AAA-ATPase. Despite intense efforts, the
      mechanism of ER exit, particularly for integral membrane (ERAD-M) substrates, has
      remained unclear. Using a self-ubiquitinating substrate (SUS), which undergoes
      normal retrotranslocation independently of known ERAD factors, and the new SPOCK
      (single plate orf compendium kit) micro-library to query all yeast genes, we
      found the rhomboid derlin Dfm1 was required for retrotranslocation of both HRD
      and DOA ERAD pathway integral membrane substrates. Dfm1 recruited Cdc48 to the ER
      membrane with its unique SHP motifs, and it catalyzed substrate extraction
      through its conserved rhomboid motifs. Surprisingly, dfm1Delta can undergo rapid
      suppression, restoring wild-type ERAD-M. This unexpected suppression explained
      earlier studies ruling out Dfm1, and it revealed an ancillary ERAD-M
      retrotranslocation pathway requiring Hrd1.

PMID- 29351851
TI  - Visualizing Dynamics of Cell Signaling In Vivo with a Phase Separation-Based
      Kinase Reporter.

PMID- 29351852
TI  - EGFR-Induced and PKCepsilon Monoubiquitylation-Dependent NF-kappaB Activation
      Upregulates PKM2 Expression and Promotes Tumorigenesis.

PMID- 29351853
TI  - Cardiac biomarkers as sensitive tools to evaluate the impact of xenobiotics on
      amphibians: the effects of anionic surfactant linear alkylbenzene sulfonate
      (LAS).
AB  - Amphibian populations have been experiencing a drastic decline worldwide. Aquatic
      contaminants are among the main factors responsible for this decline, especially
      in the aquatic environment. The linear alkylbenzene sulfonate (LAS) is of
      particular concern, since it represents 84% of the anionic surfactants' trade. In
      Brazil, the maximal LAS concentration allowed in fresh waters is 0.5mgL-1, but
      its potential harmful effects in amphibians remain unknown. Therefore, this study
      aimed to analyze the effects of a sublethal concentration of LAS (0.5mgL-1) for
      96h on sensitive cardiac biomarkers of bullfrog tadpoles, Lithobates catesbeianus
      (Shaw, 1802). For this, we measured the activity level (AL - % of animals), in
      situ heart rate (fH - bpm), relative ventricular mass (RVM - % of body mass), in
      vitro myocardial contractility and cardiac histology of the ventricles. Tadpoles'
      AL and fH decreased in LAS group. In contrast, the RVM increased, as a result of
      a hypertrophy of the myocardium, which was corroborated by the enlargement of the
      nuclear measures and the increase of myocytes' diameters. These cellular effects
      resulted in an elevation of the in vitro contractile force of ventricle strips.
      Acceleration in the contraction (TPT - ms) also occurred, although no alterations
      in the time to relaxation (THR -ms) were observed. Therefore, it can be concluded
      that even when exposed to an environmentally safe concentration, this surfactant
      promotes several alterations in the cardiac function of bullfrog tadpoles that
      can impair their development, making them more susceptible to predators and less
      competitive in terms of reproduction success. Thus, LAS concentrations that are
      considered safe by Brazilian by regulatory agencies must be revised in order to
      minimize a drastic impact over amphibian populations. This study demonstrates the
      relevance of employing cardiac biomarkers at different levels (e.g.,
      morphological, physiological and cellular) to evaluate effects of xenobiotics in
      tadpoles.

PMID- 29351854
TI  - Electric field induced charging of colloidal particles in a nonpolar liquid.
AB  - HYPOTHESIS: Colloidal particles in a pure nonpolar solvent are expected to be in
      a state of dynamic equilibrium where a particle's charge fluctuates around a
      stable mean value. However, we find that PHSA-coated PMMA microparticles in
      dodecane gain positive charge over time. We hypothesize that this phenomenon is
      prompted by the high electric field (~1 V/um) that is applied in these
      measurements. Hence, we expect the reaction rate at which charge builds up on the
      particle to change when modifying the measurement parameters. EXPERIMENTS: Single
      elementary charging and discharging events can be resolved by measuring the
      charge of PHSA-coated PMMA particles with optical trapping electrophoresis. With
      this technique, the influence of the electric field amplitude and frequency,
      particle size, electrode material and acquired charge can be investigated.
      FINDINGS: The rate of the charging phenomenon is proportional to the amplitude of
      the applied electric field and the charging stops when the voltage is switched
      off. We propose a reaction mechanism where the particle sheds negatively charged
      ions. This mechanism can account for all the experimental observations of the
      electric field induced charging phenomenon.

PMID- 29351855
TI  - The relationship of circulating fibroblast growth factor 21 levels with incident
      atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.
AB  - BACKGROUND AND AIMS: Elevated circulating levels of fibroblast growth factor 21
      (FGF21) are associated with multiple cardiovascular disease (CVD) risk factors
      and incident events. Previous small cross-sectional studies, mainly in Chinese
      populations, have suggested FGF21 may play a role in the development of atrial
      fibrillation (AF). We therefore investigated the relationship of FGF21 levels
      with incident AF in participants free of clinically apparent CVD at baseline in a
      large, multi-ethnic cohort. METHODS: A total of 5729 participants of four major
      ethnic groups (Caucasian, African American, Hispanic American, and Chinese
      American) from the Multi-Ethnic Study of Atherosclerosis (MESA), who were free of
      AF and had plasma FGF21 levels measured by ELISA at the baseline exam, were
      included in the analysis. Participants were followed up for incident AF over a
      median period of 12.9 years. Cox proportional hazards regression analysis was
      used. RESULTS: Among the 5729 participants, 778 participants developed incident
      AF. Participants with incident AF had significantly higher baseline FGF21 levels
      than those without incident AF (median = 166.0 and 142.8 pg/mL, p < 0.001). After
      adjusting for possible confounders, including demographic, socioeconomic and
      lifestyle factors, traditional CVD risk factors and circulating inflammatory
      markers, higher baseline FGF21 levels did not predict incident AF over the follow
      up period. There was no effect modification by sex or ethnicity. CONCLUSIONS:
      Baseline FGF21 levels were not associated with the development of AF in an
      ethnically diverse population followed long-term. Our findings do not support an
      important role of FGF21 in AF development.

PMID- 29351857
TI  - Psychometric properties of outcome measures evaluating decline in gait in
      cerebellar ataxia: A systematic review.
AB  - Cerebellar ataxia often results in impairment in ambulation secondary to gait
      pattern dysfunction and compensatory gait adjustments. Pharmaceutical and therapy
      based interventions with potential benefit for gait in ataxia are starting to
      emerge, however evaluation of such interventions is hampered by the lack of
      outcome measures that are responsive, valid and reliable for measurement of gait
      decline in cerebellar ataxia. This systematic review aimed for the first time to
      evaluate the psychometric properties of gait and walking outcomes applicable to
      individuals with cerebellar ataxia. Only studies evaluating straight walking were
      included. A comprehensive search of three databases (MEDLINE, CINAHL and EMBASE)
      identified 53 studies meeting inclusion criteria. Forty-nine were rated as 'poor'
      as assessed by the COnsensus-based Standards for the selection of health
      Measurement INstruments checklist. The primary objective of most studies was to
      explore changes in gait related to ataxia, rather than to examine psychometric
      properties of outcomes. This resulted in methodologies not specific for
      psychometric assessment. Thirty-nine studies examined validity, 11 examined
      responsiveness and 12 measured reliability. Review of the data identified double
      and single support and swing percentage of the gait cycle, velocity, step length
      and the Scale for Assessment and Rating of Ataxia (SARA) gait item as the most
      valid and responsive measures of gait in cerebellar ataxia. However, further
      evaluation to establish their reliability and applicability for use in clinical
      trials is clearly warranted. We recommend that inter-session reliability of gait
      outcomes should be evaluated to ensure changes are reflective of intervention
      effectiveness in cerebellar ataxia.

PMID- 29351856
TI  - High density lipoprotein with apolipoprotein C-III is associated with carotid
      intima-media thickness among generally healthy individuals.
AB  - BACKGROUND AND AIMS: About 6-7% of high density lipoprotein (HDL) has a protein
      called apolipoprotein (apo) C-III that regulates lipoprotein metabolism and can
      provoke an inflammatory response. HDL without apoC-III is inversely associated
      with coronary heart disease (CHD), whereas HDL with apoC-III is directly
      associated with CHD. We investigated how the presence of apoC-III affects the
      association between HDL and early stages of atherosclerosis measured as carotid
      intima-media thickness (cIMT). METHODS: We examined the cross-sectional
      associations between the apoA-I concentrations of HDL subspecies with and without
      apoC-III and cIMT measured by high resolution B-mode carotid ultrasonography
      among 847 participants from the European multi-center Relationship between
      Insulin Sensitivity and Cardiovascular disease (RISC) study. RESULTS: HDL with
      and without apoC-III demonstrated significantly opposite associations with both
      cIMT indexes (p-heterogeneity of associations comparing the two subspecies was
      0.002 for cIMT at common carotid artery (cIMT at CCA) and 0.006 for the maximum
      cIMT in any carotid segment (cIMT max)). Compared to the lowest quintile, the
      highest quintile of apoA-I in HDL without apoC-III was associated with 3.7% lower
      cIMT at CCA (p-trend = 0.01) or 7.3% lower cIMT max (p-trend = 0.003), while the
      highest quintile of apoA-I in HDL with apoC-III was associated with 4.4% higher
      cIMT at CCA (p-trend = 0.001) or 7.9% higher cIMT max (p-trend = 0.002). Total
      apoA-I as well as total HDL cholesterol was not associated with cIMT whereas
      higher levels of total apoC-III and apoC-III contained in HDL were significantly
      associated with higher cIMT (p-trend<0.01). CONCLUSIONS: HDL apoC-III is a
      promising target for atherosclerosis prevention and treatment.

PMID- 29351858
TI  - Determination of semicarbazide in fish by molecularly imprinted stir bar sorptive
      extraction coupled with high performance liquid chromatography.
AB  - A novel molecularly imprinted stir bar (MI-SB) for sorptive extraction of
      semicarbazide (SEM) was prepared in present paper. The coating of the stir bar
      was characterized by scanning electron microscopy, Fourier-transform infrared
      spectroscopy, dynamic adsorption and static adsorption tests. The saturated
      adsorption of MI-SB was about 4 times over that of non-imprinted stir bar (NI
      SB). The selectivity of MI-SB for SEM was much better than NI-SB. A method to
      determine SEM was established by coupling MI-SB sorptive extraction with HPLC-UV.
      The liner range was 1-100ng/mL for SEM with a correlation coefficient of 0.9985.
      The limit of detection was about 0.59ng/mL, which was below the minimum required
      performance limit of SEM in meat products regulated by European Union. The method
      was applied to the determination of SEM in fish samples with satisfactory
      results.

PMID- 29351859
TI  - Structural and immunological characterization of hydroxyl radical modified human
      IgG: Clinical correlation in rheumatoid arthritis.
AB  - Structural alterations in proteins under oxidative stress have been widely
      implicated in the immuno-pathology of various disorders. This study has evaluated
      the extent of damage in the conformational characteristics of IgG by hydroxyl
      radical (OH) and studied its implications in the immuno-pathology of rheumatoid
      arthritis (RA). Using various biophysical and biochemical techniques, changes in
      aromatic microenvironment of the IgG and the protein aggregation became evident
      after treatment with OH. The SDS-PAGE study confirmed the protein aggregation
      while far ultraviolet circular dichroism spectroscopy (Far-UV CD) and fourier
      transform infrared spectroscopy (FTIR) inferred towards the alterations in
      secondary structure of IgG under OH stress. Dynamic light scattering showed that
      the modification increased the hydrodynamic radius and polydispersity of IgG. The
      free arginine and lysine content reduced upon modification. OH induced
      aggregation was confirmed by enhanced thioflavin-T (ThT) fluorescence and red
      shift in the congo red (CR) absorbance. The study on experimental animals
      reiterates the earlier findings of enhanced immunogenicity of OH treated IgG (OH
      IgG) compared to that of native IgG. OH-IgG strongly interacted with the
      antibodies derived from the serum of 80 rheumatoid arthritis (RA) patients. The
      overwhelming and strong tendency of OH-IgG to bind the antibodies derived from
      the serum of RA patients points towards the modification of IgG under patho
      physiological conditions in RA that generate neo-epitopes and eventually cause
      the generation of auto antibodies that circulate in the patient sera. Further
      studies on this aspect may possibly lead to the development of a biomarker for
      RA.

PMID- 29351860
TI  - Microtubule dynamics: moving toward a multi-scale approach.
AB  - Microtubule self-assembly dynamics serve to facilitate many vital cellular
      functions, such as chromosome segregation during mitosis and synaptic plasticity.
      However, the detailed atomistic basis of assembly dynamics has remained an
      unresolved puzzle. A key challenge is connecting together the vast range of
      relevant length-time scales, events happening at time scales ranging from
      nanoseconds, such as tubulin molecular interactions (A-nm), to minutes-hours,
      such as the cellular response to microtubule dynamics during mitotic progression
      (MUm). At the same time, microtubule interactions with associated proteins and
      binding agents, such as anti-cancer drugs, can strongly affect this dynamic
      process through atomic-level mechanisms that remain to be elucidated. New high
      resolution technologies for investigating these interactions, including cryo
      electron microscopy (EM) techniques and total internal reflection fluorescence
      (TIRF) microscopy, are yielding important new insights. Here, we focus on recent
      studies of microtubule dynamics, both theoretical and experimental, and how these
      findings shed new light on this complex phenomenon across length-time scales,
      from A to MUm and from nanoseconds to minutes.

PMID- 29351861
TI  - Improving implementation of evidence based practice for people with psychosis
      through training the wider workforce: Results of the GOALS feasibility randomised
      controlled trial.
AB  - BACKGROUND AND OBJECTIVES: There is a pressing need to improve access to evidence
      based practice for people with psychosis. The primary aim of this study was to
      assess clinical feasibility of a manualised, evidence-based CBT intervention
      (GOALS) targeting a personalised recovery goal, delivered by the frontline
      workforce, following brief training. Secondly, we aimed to conduct preliminary
      statistical analyses of key outcomes and costs. METHODS: The GOALS study is a
      feasibility randomised controlled trial (ISRCTN 73188383). 75 participants with
      current psychosis were recruited and randomly allocated to receive either
      treatment as usual alone or with GOALS therapy. RESULTS: Brief training enabled
      frontline staff to deliver the therapy according to protocol and 74% of therapy
      participants partially or fully achieved their goals. There were significant
      improvements with a moderate effect size of 0.56 on goal attainment. However,
      preliminary statistical analyses found no significant differences between groups
      on our primary outcome of activity levels or other secondary outcomes Health
      economic analysis found that point estimates of costs, controlling for baseline
      costs, implied savings (even including intervention costs), but the difference
      was not statistically significant. LIMITATIONS: The study was designed as a
      feasibility RCT, and therefore the results of secondary estimates of efficacy
      effects should be treated with caution. CONCLUSIONS: This approach holds promise
      in supporting people with psychosis to reach personal recovery goals, cost
      effectively.

PMID- 29351862
TI  - Social capital, socioeconomic status, and depression in community-living elderly.
AB  - A growing body of evidence has suggested that social capital is an upstream
      social determinant of mental health. We investigated the association of cognitive
      social capital, including interpersonal trust and reciprocity, with depressive
      symptoms in the elderly. We also explored the mediating role of cognitive social
      capital in the association between socioeconomic status (SES) and depressive
      symptoms and the moderating effect of SES on the relationship between social
      capital and depressive symptoms. Data from the 2012 Korea Welfare Panel Study
      (KOWEPS) was analyzed for 5969 participants aged 60 years or older. Cognitive
      components of social capital, including interpersonal trust and reciprocity, were
      evaluated using single-item questionnaires. Socioeconomic and health-related
      characteristics were investigated and depressive symptoms were evaluated by an 11
      item version of the Center for Epidemiologic Studies Depression Scale. Low
      interpersonal trust and reciprocity levels were significantly associated with
      depressive symptoms in the elderly. Reciprocity level mediated the association
      between household income level and depressive symptoms. We did not observe any
      significant moderating effect of SES on the association between cognitive social
      capital and depressive symptoms. A significant association between cognitive
      social capital and depressive symptoms in Korean elderly was found. We elucidated
      how SES interacted with depressive symptoms through the mediation pathway of
      cognitive social capital using a representative sample of the Korean elderly
      population.

PMID- 29351863
TI  - Size congruity influences visual search via the target template.
AB  - In numerical comparison experiments, participants are presented with two digits
      that vary in numerical and physical size, and they select the numerically (or
      physically) larger (or smaller) of the two digits. Response times are typically
      faster when numerical and physical size are congruent than when they are
      incongruent, which is called the size congruity effect (SCE). Although numerical
      size is unlikely to be a guiding feature in visual search, recent studies have
      nevertheless observed the SCE in the visual search paradigm. To explain this
      puzzling fact, we hypothesized that the incongruity between a target's numerical
      and physical size affects visual search primarily when an attended item is
      compared to the target template in visual short-term memory. In three
      experiments, participants searched for a target whose numerical and physical size
      were distinct from non-target distractors. The SCE and shallow search slopes in
      Experiment 1 suggest that the target's physical size captured attention, and only
      then did incongruent numerical size interfere with the response. Instructing
      participants to attend to physical size in Experiment 2 abolished the SCE,
      suggesting that participants did not analyze the target's numerical size when
      they could be confident that physical size was a reliable target cue. Presenting
      each of two possible target digits in blocks as in Experiment 3 enabled
      participants to load the visual features of shape and physical size into their
      target template, and once again the SCE was abolished. The three experiments show
      that the SCE in visual search can be reduced or eliminated by restricting the
      target template based on specific physical features and thus discouraging
      participants from analyzing the target's numerical size.

PMID- 29351864
TI  - Prolonging the response movement inhibits the feed-forward motor program in the
      sustained attention to response task.
AB  - Despite widespread use in clinical and experimental contexts, debate continues
      over whether or not the Sustained Attention to Response Task (SART) successfully
      measures sustained attention. Altering physical aspects of the response movement
      required to SART stimuli may help identify whether performance is a better
      measure of perceptual decoupling, or response strategies and motor inhibition.
      Participants completed a SART where they had to manually move a mouse cursor to
      respond to stimuli, and another SART where this extra movement was not required,
      as in a typical SART. Additionally, stimuli were located at either a close or a
      far distance away. Commission errors were inversely related to distance in the
      manual movement condition, as the farther distance led to longer response times
      which gave participants more time to inhibit prepotent responses and thus prevent
      commission errors. Self-reported measures of mental demand and fatigue suggested
      there were no differences in mental demands between the manual and automatic
      condition; instead the differences were primarily in physical demands. No
      differences were found for task-unrelated thoughts between the manual and
      automatic condition. The movement effect combined with participants' subjective
      reports are evidence for time dependent action stopping, not greater cognitive
      engagement. These findings support a response strategy perspective as opposed to
      a perceptual decoupling perspective, and have implications for authors
      considering using the SART. Applied implications of this research are also
      discussed.

PMID- 29351866
TI  - Bioanalysis of a panel of neurotransmitters and their metabolites in plasma
      samples obtained from pediatric patients with neuroblastoma and Wilms' tumor.
AB  - This paper details the quantitative analysis of neurotransmitters, including
      dopamine (DA), norepinephrine (NE), epinephrine (E), and serotonin (5-HT), along
      with their respective precursors and metabolites in children with solid tumors:
      Wilms' tumor (WT) and neuroblastoma (NB). A panel of neurotransmitters was
      determined with the use of dispersive liquid-liquid microextraction (DLLME)
      technique combined with liquid-chromatography mass spectrometry (LC-MS/MS) in
      plasma samples obtained from a group of pediatric subjects with solid tumors and
      a control group of healthy children. Next, statistical univariate analysis (t
      test) and multivariate analysis (Principal Component Analysis) were performed
      using chromatographic data. The levels of tyrosine (Tyr) and tryptophan (Trp)
      (the precursors of analyzed neurotransmitters) as well as 3,4
      dihydroxyphenylacetic acid (DOPAC) (a product of metabolism of DA) were
      significantly higher in the plasma samples obtained from pediatric patients with
      WT than in the samples taken from the control group. Moreover, statistically
      significant differences were observed between the levels of 5-HT and homovanillic
      acid (HVA) in the plasma samples from pediatric patients with solid tumors and
      the control group. However, elevated levels of these analytes did not facilitate
      a clear distinction between pediatric patients with WT and those with NB.
      Nonetheless, the application of advanced statistical tools allowed the healthy
      controls to be differentiated from the pediatric oncological patients. The
      identification and quantification of a panel of neurotransmitters as potential
      prognostic factors in selected childhood malignancies may provide clinically
      relevant information about ongoing metabolic alterations, and it could
      potentially serve as an adjunctive strategy in the effective diagnosis and
      treatment of solid tumors in children.

PMID- 29351865
TI  - Interventions to support effective communication between maternity care staff and
      women in labour: A mixed-methods systematic review.
AB  - OBJECTIVES: the objectives of this review were (1) to assess whether
      interventions to support effective communication between maternity care staff and
      healthy women in labour with a term pregnancy could improve birth outcomes and
      experiences of care; and (2) to synthesize information related to the feasibility
      of implementation and resources required. DESIGN: a mixed-methods systematic
      review. SETTING AND PARTICIPANTS: studies which reported on interventions aimed
      at improving communication between maternity care staff and healthy women during
      normal labour and birth, with no apparent medical or obstetric complications, and
      their family members were included. 'Maternity care staff' included medical
      doctors (e.g. obstetricians, anaesthetists, physicians, family doctors,
      paediatricians), midwives, nurses and other skilled birth attendants providing
      labour, birth and immediate postnatal care. Studies from all birth settings (any
      country, any facility including home birth, any resource level) were included.
      FINDINGS: two papers met the inclusion criteria. One was a step wedge randomised
      controlled trial conducted in Syria, and the other a sub-analysis of a randomised
      controlled trial from the United Kingdom. Both studies aimed to assess effects of
      communication training for maternity care staff on women's experiences of labour
      care. The study from Syria reported that a communication skills training
      intervention for resident doctors was not associated with higher satisfaction
      reported by women. In the UK study, patient-actors' (experienced midwives)
      perceptions of safety and communication significantly improved for postpartum
      haemorrhage scenarios after training with patient-actors in local hospitals,
      compared with training using manikins in simulation centres, but no differences
      were identified for other scenarios. Both studies had methodological limitations.
      KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: the review identified a lack of
      evidence on impact of interventions to support effective communication between
      maternity care staff and healthy women during labour and birth. Very low quality
      evidence was found on effectiveness of communication training of maternity care
      staff. Robust studies which are able to identify characteristics of interventions
      to support effective communication in maternity care are urgently needed.
      Consideration also needs to be given to how organisations prepare, monitor and
      sustain interventions to support effective communication, which reflect outcomes
      of priority for women, local culture and context of labour and birth care.

PMID- 29351867
TI  - Electrosynthesized MIPs for transferrin: Plastibodies or nano-filters?
AB  - Molecularly imprinted polymer (MIP) nanofilms for transferrin (Trf) have been
      synthesized on gold surfaces by electro-polymerizing the functional monomer
      scopoletin in the presence of the protein target or around pre-adsorbed Trf. As
      determined by atomic force microscopy (AFM) the film thickness was comparable
      with the molecular dimension of the target. The target (re)binding properties of
      the electro-synthesized MIP films was evaluated by cyclic voltammetry (CV) and
      square wave voltammetry (SWV) through the target-binding induced permeability
      changes of the MIP nanofilms to the ferricyanide redox marker, as well as by
      surface plasmon resonance (SPR) and surface enhanced infrared absorption
      spectroscopy (SEIRAS) of the immobilized protein molecules. For Trf a linear
      concentration dependence in the lower micromolar range and an imprinting factor
      of ~5 was obtained by SWV and SPR. Furthermore, non-target proteins including the
      iron-free apo-Trf were discriminated by pronounced size and shape specificity.
      Whilst it is generally assumed that the rebinding of the target or of cross
      reacting proteins exclusively takes place at the polymer here we considered also
      the interaction of the protein molecules with the underlying gold transducers. We
      demonstrate by SWV that adsorption of proteins suppresses the signal of the redox
      marker even at the bare gold surface and by SEIRAS that the treatment of the MIP
      with proteinase K or NaOH only partially removes the target protein. Therefore,
      we conclude that when interpreting binding of proteins to directly MIP-covered
      gold electrodes the interactions between the protein and the gold surface should
      also be considered.

PMID- 29351868
TI  - An aptamer nanopore-enabled microsensor for detection of theophylline.
AB  - This paper reports an aptamer-based nanopore thin film sensor for detecting
      theophylline in the buffer solution and complex fluids including plant extracts
      and serum samples. Compared to antibody-based detection, aptamer-based detection
      offers many advantages such as low cost and high stability at elevated
      temperatures. Experiments found that this type of sensor can readily detect
      theophylline at a concentration as low as 0.05uM, which is much lower than the
      detection limit of current lab-based equipment such as liquid chromatography
      (LC). Experiments also found that the aptamer-based sensor has good specificity,
      selectivity, and reasonable reusability with a significantly improved dynamic
      detection range. By using the same nanopore thin film sensors as the reference
      sensors to further mitigate the non-specific binding effect, the theophylline in
      plant extracts and serum has been detected. Only a small amount (~1MUL) of plant
      extracts or serum samples is required to measure theophylline. Its low cost and
      ease-of-operation make this type of sensor suitable for point-of-care application
      to monitor the theophylline level of patients in real time.

PMID- 29351869
TI  - Allosteric kissing complex-based electrochemical biosensor for sensitive,
      regenerative and versatile detection of proteins.
AB  - Herein, an allosteric kissing complex-based electrochemical biosensor was
      ingeniously proposed for the simple, sensitive, regenerative and versatile
      detection of proteins. Two hairpins (Hp1 and Hp2) were designed and the Hp1 was
      immobilized on the electrode surface, which could form a kissing complex with Hp2
      through the apical loop-loop or kissing interaction of the RNA-RNA base
      sequences. The Hp2 possesses the appended single-stranded tails on each end,
      which hybridize with the recognition element-conjugated DNA strands to construct
      a protein responsive switch of Hp2 scaffold. After kissing complex formation
      between the Hp2 scaffold and the immobilized Hp1, the streptavidin-labeled
      alkaline phosphatase (SA-ALP) can be introduced onto the electrode surface for
      the generation of electrochemical signal. In the presence of target protein, its
      binding to the recognition elements linked onto the Hp2 scaffold endows the
      steric strain to open the Hp2 stem, propagated by the disruption of the kissing
      complex structure, resulting into a decreased electrochemical signal related with
      the protein quantification. Also, the Hp1 immobilized electrode can be directly
      regenerated after protein-induced kissing complex dissociation. The current
      kissing complex-based electrochemical biosensing strategy can be easily extended
      for the detection toward different protein targets of interest by simply changing
      the recognition elements conjugated onto the Hp2 scaffold. The sensitive and
      selective detection toward proteins could be achieved with the detection limits
      toward Anti-Dig antibody and thrombin of about 1ng/mL and 10pM, respectively. The
      developed kissing complex-based protein biosensing strategy should be a
      beneficial supplement in current biosensor field, providing a promising means for
      the applications in bioanalysis, disease diagnostics, and clinical biomedicine.

PMID- 29351870
TI  - De novo generation in an in vivo rat model and biomechanical characterization of
      autologous transplants for ligament and tendon reconstruction.
AB  - BACKGROUND: Surgical reconstruction of ligaments and tendons is frequently
      required in clinical practice. The commonly used autografts, allografts, or
      synthetic transplants present limitations in terms of availability,
      biocompatibility, cost, and mechanical properties that tissue bioengineering aims
      to overcome. It classically combines an exogenous extracellular matrix with
      cells, but this approach remains complex and expensive. Using a rat model, we
      tested a new bioengineering strategy for the in vivo and de novo generation of
      autologous grafts without the addition of extracellular matrix or cells, and
      analyzed their biomechanical and structural properties. METHODS: A silicone
      perforated tubular implant (PTI) was designed and implanted in the spine of male
      Wistar rats to generate neo-transplants. The tensile load to failure, stiffness,
      Young modulus, and ultrastructure of the generated tissue were determined at 6
      and 12weeks after surgery. The feasibility of using the transplant that was
      generated in the spine as an autograft for reconstruction of medial collateral
      ligaments (MCL) and Achilles tendons was also tested. FINDINGS: Use of the PTI
      resulted in de novo transplant generation. Their median load to failure and Young
      modulus increased between 6 and 12weeks (respectively 12N vs 34N and 48MPa vs
      178MPa). At 12weeks, the neo-transplants exhibited collagen bundles (mainly type
      III) parallel to their longitudinal axis and elongated fibroblasts. Six weeks
      after their transfer to replace the MCL or the Achilles tendon, the transplants
      were still present, with their ends healed at their insertion point.
      INTERPRETATION: This animal study is a first step in the design and validation of
      a new bioengineering strategy to develop autologous transplants for ligament and
      tendon reconstructions.

PMID- 29351871
TI  - Systemic signaling in response to wounding and pathogens.
AB  - Plants possess systemic signaling networks that allow the perception of local
      stresses to be translated into plant-wide responses. Although information can be
      propagated via a variety of molecules such as hormones and RNAs moving within the
      bulk flow of the phloem or in the transpiration stream, the vasculature also
      appears to be a major pathway whereby extremely rapid signals move bi
      directionally throughout the plant. In these cases, the movement mechanisms are
      not dependent on redistribution through bulk flow. For example, self-reinforcing
      systems based around changes in Ca2+ and reactive oxygen species, coupled to
      parallel electrical signaling events appear able to generate waves of information
      that can propagate at hundreds of MUm/s. These signals then elicit distant
      responses that prime the plant for a more effective defense or stress response in
      unchallenged tissues. Although ion channels, Ca2+, reactive oxygen species and
      associated molecular machineries, such as the NADPH oxidases, have been
      identified as likely important players in this propagation system, the precise
      nature of these signaling networks remains to be defined. Critically, whether
      different stimuli are using the same rapid, systemic signaling network, or
      whether multiple, parallel pathways for signal propagation are operating to
      trigger specific systemic outputs remains a key open question.

PMID- 29351873
TI  - Biochar amendment for batch composting of nitrogen rich organic waste: Effect on
      degradation kinetics, composting physics and nutritional properties.
AB  - Composting is an efficient technology to reduce pathogenic bodies and stabilize
      the organic matter in organic wastes. This research work investigates an effect
      of biochar as amendment to improve the composting efficiency and its effect on
      degradation kinetics, physical and nutritional properties. Biochar (2.5, 5 and
      10% (w/w)) were added into a mixture of Hydrilla verticillata, cow dung and
      sawdust having ratio of 8:1:1 (control), respectively. Biochar addition resulted
      in advanced thermophilic temperatures (59  degrees C) and could improve the
      physical properties of composting process. Owing to addition of 5% biochar as a
      bulking agent in composting mixture, the final product from composting, total
      nitrogen increased by 45% compared to the other trials, and air-filled porosity
      decreased by 39% and was found to be within recommended range from literature
      studies. Considering temperature, degradation rate and nitrogen transformation
      the amendment of 5% biochar is recommended for Hydrilla verticillata composting.

PMID- 29351872
TI  - Low cortical iron and high entorhinal cortex volume promote cognitive functioning
      in the oldest-old.
AB  - The aging brain is characterized by an increased presence of neurodegenerative
      and vascular pathologies. However, there is substantial variation regarding the
      relationship between an individual's pathological burden and resulting cognitive
      impairment. To identify correlates of preserved cognitive functioning at highest
      age, the relationship between beta-amyloid plaque load, presence of small vessel
      cerebrovascular disease (SVCD), iron-burden, and brain atrophy was investigated.
      Eighty cognitively unimpaired participants (44 oldest-old, aged 85-96 years; 36
      younger-old, aged 55-80 years) were scanned by integrated positron emission
      tomography-magnetic resonance imaging for assessing beta regional amyloid plaque
      load (18F-flutemetamol), white matter hyperintensities as an indicator of SVCD
      (fluid-attenuated inversion recovery-magnetic resonance imaging), and iron load
      (quantitative susceptibility mapping). For the oldest-old group, lower cortical
      volume, increased beta-amyloid plaque load, prevalence of SVCD, and lower
      cognitive performance in the normal range were found. However, compared to normal
      old, cortical iron burden was lower in the oldest-old. Moreover, only in the
      oldest-old, entorhinal cortex volume positively correlated with beta-amyloid
      plaque load. Our data thus indicate that the co-occurrence of aging-associated
      neuropathologies with reduced quantitative susceptibility mapping measures of
      cortical iron load constitutes a lower vulnerability to cognitive loss.

PMID- 29351874
TI  - Phenol preparation from catalytic pyrolysis of palm kernel shell at low
      temperatures.
AB  - In the present study, the characteristics of phenol preparation from palm kernel
      shell (PKS) pyrolysis at the temperature range of 265-320  degrees C were
      investigated using TG-FTIR-MS analyses, based on the analysis about the
      decomposition characteristics of PKS comparing to other biomass samples. The GC
      MS analysis was subsequently employed to qualitatively and quantitatively
      characterize the phenol in bio-oils from PKS catalytic pyrolysis at 265-320 
      degrees C. Two significant weight loss peaks with the closer values were observed
      in DTG curve of PKS that differentiated with other samples, which was mainly
      attributed to the content and especially the structural characteristics of lignin
      in the PKS. Phenol was mainly in bio-oils from decomposition of the "first weight
      loss peak" during PKS pyrolysis at 265-320  degrees C. The relative content in
      bio-oil, selectivity in phenolic compounds, and mass yield of phenol from PKS
      catalytic pyrolysis with CaO could reach to 83.21 area%, 100%, and 0.0075 g/(g
      biomass), respectively.

PMID- 29351875
TI  - Trunk and pelvic dynamics during transient turns among individuals with
      unilateral traumatic lower limb amputation.
AB  - Prior work has identified alterations in trunk-pelvic dynamics with lower limb
      amputation (LLA) during in-line walking; however, evaluations of other ambulatory
      tasks are limited. Turns are ubiquitous in daily life but can be challenging for
      individuals with LLA, prompting additional or unique proximal compensations when
      changing direction, which over time may lead to development of low back pain. We
      hypothesized such proximal kinematic differences between persons with and without
      LLA would exist in the sagittal and frontal planes. Three-dimensional trunk and
      pelvic kinematics, translational and rotational momenta, and coordination
      phase/variability were compared among eight persons with unilateral LLA (4 with
      transfemoral amputation and 4 with transtibial amputation), and five uninjured
      controls, who performed 90-degree turns to the left (n = 10) and right (n = 10).
      Participants self-selected the turn strategy (i.e., step vs. spin) and pivot limb
      in response to verbal cues regarding when and which direction to turn.
      Coordination variability and translational angular momenta did not differ between
      groups in either turn type. During spin turns, frontal rotational angular momenta
      were larger and frontal trunk-pelvis range of motion was smaller among persons
      with vs. without LLA. During step turns, pelvis leading transverse coordination
      was more frequent, frontal trunk rotational angular momentum was smaller, and
      sagittal pelvis range of motion was larger among persons with vs. without LLA.
      Altered and task-dependent modulation of trunk-pelvic dynamics among persons with
      LLA provides additional support for a potential link between repeated exposures
      to altered trunk-pelvic dynamics with elevated low back pain risk.

PMID- 29351876
TI  - Vital signs analysis algorithm detects inflammatory response in premature infants
      with late onset sepsis and necrotizing enterocolitis.
AB  - BACKGROUND: Nonspecific clinical signs and suboptimal diagnostic tests limit
      accurate identification of late onset sepsis (LOS) and necrotizing enterocolitis
      (NEC) in premature infants, resulting in significant morbidity and antibiotic
      overuse. An infant's systemic inflammatory response may be identified earlier
      than clinical suspicion through analysis of multiple vital signs by a
      computerized algorithm (RALIS). AIM: To evaluate the revised RALIS algorithm for
      detection of LOS and NEC in preterm infants. METHODS: In this nested case-control
      study, VS data (heart rate, respiratory rate, temperature, desaturations,
      bradycardias) were extracted from medical records of infants 23-32 weeks
      gestation. RALIS generated an output, with score >= 5 triggering an alert.
      Patient episodes were classified based on culture, radiograph, and antibiotic
      data into categories: LOS, expanded LOS, NEC, and controls. Paired t-tests,
      linear regression and cross-validation analyses were used to evaluate the
      relationship between RALIS alert and LOS/NEC. RESULTS: Among 155 infants with 161
      episodes, there were 41 expanded LOS (+blood, CSF, urine, respiratory culture),
      31 LOS (+blood, CSF, urine), 9 NEC, and 93 controls. RALIS alert was 43.1 +/- 79
      h before culture in LOS (p = .012). There was a significant association between
      RALIS alert and LOS/NEC (beta = 0.72, p < .0001). Sensitivity and specificity for
      LOS/NEC were 84% and 80%, (PPV = 63%; NPV = 93%). The regression model
      demonstrated an AUC of 89.9%. CONCLUSIONS: For infants <=32 weeks, RALIS detects
      systemic inflammatory responses in LOS and NEC in the first month of life. The
      algorithm can identify infection earlier than clinical suspicion, even for NEC
      with negative cultures. RALIS has high NPV to rule-out LOS and NEC, and may,
      after prospective validation, aid in antibiotic treatment decisions.

PMID- 29351878
TI  - Kinetic studies of the AOP radical-based oxidative and reductive destruction of
      pesticides and model compounds in water.
AB  - Absolute second-order rate constants for hydroxyl radical (HO) reaction with four
      organophosphorus pesticides, malathion, parathion, fenthion and ethion, and a
      suite of model compounds of structure (EtO)2P(S)-X (where X = Cl, F, SH, SEt,
      OCH2CF3, OEt, NH2, and CH3) were measured using electron pulse radiolysis and
      transient absorption techniques. Specific values were determined for these four
      pesticides as k = (3.89 +/- 0.28) x 109, (2.20 +/- 0.15) x 109, (2.02 +/- 0.15) x
      109 and (2.93 +/- 0.10) x 109 M-1 s-1, respectively, at 20 +/- 2  degrees C. The
      corresponding Bronsted plot for all these compounds demonstrated that the HO
      oxidation reaction mechanism for the pesticides was consistent with the model
      compounds, attributed to initial HO-adduct formation at the P(S) moiety. For
      malathion, steady-state 60Co radiolysis and 31P NMR analyses showed that hydroxyl
      radical-induced oxidation produces the far more potent isomalathion, but only
      with an efficiency of 4.9 +/- 0.3%. Analogous kinetic measurements for the
      hydrated electron induced reduction of these pesticides gave specific rate
      constants of k = (3.38 +/- 0.14) x 109, (1.38 +/- 0.10) x 109, (1.19 +/- 0.12) x
      109 and (1.20 +/- 0.06) x 109 M-1 s-1, respectively, for malathion, parathion,
      fenthion and ethion. Model compound measurements again supported a single
      reduction reaction mechanism, proposed to be electron addition at the PS bond to
      form the radical anion. These results demonstrate, for the first time, that the
      radical-based treatment of organophosphorus contaminated waters may present a
      potential toxicological risk if advanced oxidative processes are used.

PMID- 29351877
TI  - REST, a master transcriptional regulator in neurodegenerative disease.
AB  - The restrictive element-1 silencing transcription factor)/NRSF (neuron
      restrictive silencing factor (NRSF) is a transcriptional repressor which acts via
      epigenetic remodeling to silence target genes. Emerging evidence indicates that
      REST is a master transcriptional regulator of neuron-specific genes not only in
      neurogenesis and neuronal differentiation, but also in differentiated neurons
      during the critical period in postnatal brain development, where it plays a role
      in fine-tuning of genes involved in synaptic plasticity, and in normal aging,
      where it promotes neuroprotection by repressing genes involved in oxidative
      stress and beta-amyloid toxicity. This review focuses on recent findings that
      dysregulation of REST and REST-dependent epigenetic remodeling provide a central
      mechanism critical to the progressive neurodegeneration associated with
      neurologic disorders and diseases including global ischemia, stroke, epilepsy,
      Alzheimer's and Huntington's disease.

PMID- 29351879
TI  - The importance of monochromatic lights in the production of phenolic acids and
      flavonoids in shoot cultures of Aronia melanocarpa, Aronia arbutifolia and Aronia
      * prunifolia.
AB  - Shoot cultures of Aronia melanocarpa, A. arbutifolia and A. * prunifolia were
      maintained on Murashige and Skoog medium with 1 mg/l each of BA and NAA under
      monochromatic lights (far-red, red, blue lights, UV-A-irradiation), in darkness,
      and under white light (control). HPLC-DAD analyses of 19 phenolic acids and 11
      flavonoids in methanolic extracts from the shoots revealed in all of them the
      presence of three depsides (chlorogenic, neochlorogenic and rosmarinic acids),
      protocatechuic acid, four flavonoid glycosides (cynaroside, quercitrin,
      hyperoside and rutoside), and additionally, in A. arbutifolia, 3,4
      dihydroxyphenylacetic acid. Depending on light quality, the total amounts of
      these metabolites increased 1.8-5.9 times, reaching maximum values under blue
      light: 527.40 and 144.61 mg 100 g-1 DW (A. melanocarpa), 543.27 and 85.82 mg 100
      g-1 DW (A. arbutifolia) and 1615.18 and 220.65 mg 100 g-1 DW (A. * prunifolia),
      respectively. The maximum total amounts were 1.3-3.6 times higher than under
      white light. The quantities of individual metabolites changed from 1.2 to 11.0
      times, with high amounts of neochlorogenic acid and quercitrin in A. melanocarpa
      (243.35 and 75.64 mg 100 g-1 DW), and of chlorogenic and rosmarinic acids and
      quercitrin in A. arbutifolia (236.52, 219.35 and 51.01 mg 100 g-1 DW). Extremely
      high amounts of depsides (418.83, 644.68, 548.86 mg 100 g-1 DW) and quercitrin
      (165.88 mg 100 g-1 DW) were produced in cultures of the hybrid - A. * prunifolia.
      The results are potentially useful for practical applications. This is the first
      report documented the importance of light quality on the production of phenolic
      acids and flavonoids in three aronia in vitro cultures.

PMID- 29351880
TI  - Preparation and characterization of biocompatible silver nanoparticles using
      pomegranate peel extract.
AB  - The potential application of any nanoparticles, including silver nanoparticles
      (AgNPs), strongly depends on their stability against aggregation. In the current
      study, an aqueous extract of pomegranate peel was used as a stabilizer during
      synthesis of AgNPs. Nanoparticles have been prepared by the chemical reduction
      method from an aqueous solution of silver nitrate in the presence of sodium
      borohydride as a reducing agent. The AgNPs were characterized by dynamic light
      scattering (DLS), zeta-potential measurements, UV-Vis spectroscopy and
      transmission electron microscopy (TEM). The antibacterial efficiency of AgNPs
      against Escherichia coli was investigated. The size, polydispersity index, FWHM,
      and colloidal stability of nanoparticles in dispersion depends on the extract
      concentrations. In the presence of pomegranate peel extract, the nanoparticles
      suspension shows colloidal stability at least for a week. Our studies show that
      synthesized AgNPs with the above described procedure were stable at pH = 3-12 and
      in the temperature range of 25-85  degrees C. Additionally, AgNPs exhibit
      antibacterial properties, especially at the lowest amount of extract to silver
      ratio (KExtract/Ag).

PMID- 29351882
TI  - Surface characterization of arsenopyrite during chemical and biological
      oxidation.
AB  - The surface properties of arsenopyrite during chemical and biological oxidation
      were investigated by synchrotron X-ray diffraction (S-XRD), X-ray absorption near
      edge structure (XANES) and scanning electron microscope (SEM), accompanying with
      leaching behaviors elucidation. The moderate thermophile S. thermosulfidooxdians
      was used as the bioleaching microorganism. Leaching experiments showed that only
      16.26% and 44.37% of total arsenic extractions were obtained for sterile acid and
      culture medium controls, whereas 79.20% of total arsenic was recovered at the end
      of bioleaching. SEM indicated that new products were layered on the surface of
      arsenopyrite after chemical and biological oxidation. As displayed in S-XRD
      patterns, scorodite and elemental sulfur were formed after acid leaching, while
      only elemental sulfur was detected in the residue leached by acid culture medium.
      During bioleaching, elemental sulfur was produced from day 4 and jarosite was
      produced from day 9. The results of iron and arsenic L-edge XANES were in good
      consistence with S-XRD. The accumulation of scorodite and jarosite on
      arsenopyrite surface should be the main reason for the hindered dissolution of
      arsenopyrite during acid leaching and bioleaching. These studies are pretty
      meaningful for better understanding the oxidation mechanism of arsenopyrite and
      evaluating arsenic risk to the environment.

PMID- 29351881
TI  - Phonotactic processing deficit following left-hemisphere stroke.
AB  - The neural basis of speech processing is still a matter of great debate.
      Phonotactic knowledge-knowledge of the allowable sound combinations in a language
      remains particularly understudied. The purpose of this study was to investigate
      the brain regions crucial to phonotactic knowledge in left-hemisphere stroke
      survivors. Results were compared to areas in which gray matter anatomy related to
      phonotactic knowledge in healthy controls. 44 patients with chronic left
      hemisphere stroke, and 32 controls performed an English-likeness rating task on
      60 auditory non-words of varying phonotactic regularities. They were asked to
      rate on a 1-5 scale, how close each non-word sounded to English. Patients'
      performance was compared to that of healthy controls, using mixed effects
      modeling. Multivariate lesion-symptom mapping and voxel-based morphometry were
      used to find the brain regions important for phonotactic processing in patients
      and controls respectively. The results showed that compared to controls, stroke
      survivors were less sensitive to phonotactic regularity differences. Lesion
      symptom mapping demonstrated that a loss of sensitivity to phonotactic
      regularities was associated with lesions in left angular gyrus and posterior
      middle temporal gyrus. Voxel-based morphometry also revealed a positive
      correlation between gray matter density in left angular gyrus and sensitivity to
      phonotactic regularities in controls. We suggest that the angular gyrus is used
      to compare the incoming speech stream to internal predictions based on the
      frequency of sound sequences in the language derived from stored lexical
      representations in the posterior middle temporal gyrus.

PMID- 29351883
TI  - Titanium dioxide nanoparticle exposure reduces algal biomass and alters algal
      assemblage composition in wastewater effluent-dominated stream mesocosms.
AB  - A 5-week mesocosm experiment was conducted to investigate the toxicity of
      titanium dioxide nanoparticles (TiO2NPs) to periphytic algae in an
      environmentally-realistic scenario. We used outdoor experimental streams to
      simulate the characteristics of central Texas streams receiving large discharges
      of wastewater treatment plant effluent during prolonged periods of drought. The
      streams were continually dosed and maintained at two concentrations. The first
      represents an environmentally relevant concentration of 0.05 mg L-1 (low
      concentration). The second treatment of 5 mg L-1 (high concentration) was
      selected to represent a scenario where TiO2NPs are used for photocatalytic
      degradation of pharmaceuticals in wastewater. Algal cell density, chlorophyll-a,
      ash-free dry mass, algal assemblage composition, and Ti accumulation were
      determined for the periphyton in the riffle sections of each stream. The high
      concentration treatment of TiO2NPs significantly decreased algal cell density,
      ash-free dry mass, and chlorophyll-a, and altered algal assemblage composition.
      Decreased abundance of three typically pollution-sensitive taxa and increased
      abundance of two genera associated with heavy metal sorption and organic
      pollution significantly contributed to algal assemblage composition changes in
      response to TiO2NPs. Benefits of the use of TiO2NPs in wastewater treatment
      plants will need to be carefully weighed against the demonstrated ability of
      these NPs to cause large changes in periphyton that would likely propagate
      significant effects throughout the stream ecosystem, even in the absence of
      direct toxicity to higher trophic level organisms.

PMID- 29351884
TI  - Crucial role of chelatable iron in silver nanoparticles induced DNA damage and
      cytotoxicity.
AB  - Damage to mitochondria and subsequent ROS leakage is a commonly accepted
      mechanism of nanoparticle toxicity. However, malfunction of mitochondria results
      in generation of superoxide anion radical (O2*-), which due to the relatively low
      chemical reactivity is rather unlikely to cause harmful effects triggered by
      nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles
      (AgNPs) resulted in generation of H2O2 instead of O2*-, as measured by ROS
      specific mitochondrial probes. Moreover, addition of a selective iron chelator
      diminished AgNPs toxicity. Altogether these results suggest that O2*- generated
      during NPs induced mitochondrial collapse is rapidly dismutated to H2O2, which in
      the presence of iron ions undergoes a Fenton reaction to produce an extremely
      reactive hydroxyl radical (*OH). Clarification of the mechanism of NPs-dependent
      generation of *OH and demonstration of the crucial role of iron ions in NPs
      toxicity will facilitate our understanding of NPs toxicity and the design of safe
      nanomaterials.

PMID- 29351885
TI  - Repetitive TMS to augment cognitive processing therapy in combat veterans of
      recent conflicts with PTSD: A randomized clinical trial.
AB  - BACKGROUND: The objective was to test whether repetitive Transcranial Magnetic
      Stimulation (rTMS) just prior to Cognitive Processing Therapy (CPT) would
      significantly improve the clinical outcome compared to sham rTMS prior to CPT in
      veterans with PTSD. METHODS: Veterans 18-60 years of age with current combat
      related PTSD symptoms were randomized, using a 1:1 ratio in a parallel design, to
      active (rTMS+CPT) versus sham (sham+CPT) rTMS just prior to weekly CPT for 12-15
      sessions. Blinded raters evaluated veterans at baseline, after the 5th and 9th
      treatments, and at 1, 3, and 6 months post-treatment. Clinician Administered PTSD
      Scale (CAPS) was the primary outcome measure with the PTSD Checklist (PCL) as a
      secondary outcome measure. The TMS coil (active or sham) was positioned over the
      right dorsolateral prefrontal cortex (110% MT, 1Hz continuously for 30min, 1800
      pulses/treatment). RESULTS: Of the 515 individuals screened for the study, 103
      participants were randomized to either active (n = 54) or sham rTMS (n = 49).
      Sixty-two participants (60%) completed treatment and 59 (57%) completed the 6
      month assessment. The rTMS+CPT group showed greater symptom reductions from
      baseline on both CAPS and PCL across CPT sessions and follow-up assessments, t(df
      >= 325) <= -2.01, p <= 0.023, one-tailed and t(df >= 303) <= -2.14, p <= 0.017,
      one-tailed, respectively. LIMITATIONS: Participants were predominantly male and
      limited to one era of conflicts as well as those who could safely undergo rTMS.
      CONCLUSIONS: The addition of rTMS to CPT compared to sham with CPT produced
      significantly greater PTSD symptom reduction early in treatment and was sustained
      up to six months post-treatment.

PMID- 29351886
TI  - Self-harm among the homeless population in Ireland: A national registry-based
      study of incidence and associated factors.
AB  - BACKGROUND: Self-harm is a strong predictor of future suicide, but little is
      known about self-harm among the homeless population. The study aim was to
      estimate the incidence of self-harm among the homeless population and to assess
      factors associated with self-harm. METHODS: Data on self-harm presentations to 34
      hospital emergency departments in Ireland were collected by the National Self
      Harm Registry Ireland (NSHRI). Index presentations between 2010 and 2014 were
      included for the homeless and fixed residence populations. Incidence rates of
      self-harm were calculated using NSHRI data and census estimates. Factors
      associated with self-harm and repeated self-harm were analysed by multivariable
      adjusted logistic regression. RESULTS: The age-standardised incidence rate of
      self-harm was 30 times higher among the homeless (5572 presentations per 100,000)
      compared with those with a fixed residence (187 presentations per 100,000).
      Homeless people had significantly higher odds of being male (OR 1.86, 95%CI 1.56
      2.23), presenting with self-cutting (vs. overdose, OR 2.15, 95%CI 1.74-2.66) and
      having psychiatric admission (vs. general admission, OR 2.43, 95%CI 1.66-3.57).
      Homeless people had higher odds of self-harm repetition within 12 months (vs.
      fixed residence, OR 1.46, 95%CI 1.21-1.77). The odds of repetition were
      significantly increased among homeless who engaged in self-cutting (vs. overdose,
      OR 1.76, 95%CI 1.17-2.65) and did not receive psychiatric review at index
      presentation (vs. reviewed, OR 1.54, 95%CI 1.05-2.26). LIMITATIONS: The study
      only reflects self-harm presenting to hospital, and assumes no change in
      homelessness status after index presentation. Residual confounding may affect the
      results. CONCLUSION: There is a disproportionate burden of self-harm among the
      homeless. Targeted preventive actions are warranted.

PMID- 29351887
TI  - Synthesis and anti-tumor activity of EF24 analogues as IKKbeta inhibitors.
AB  - EF24 is an IKKbeta inhibitor (IC50: 72 MUM) containing various anti-tumor
      activities. In this study, a series of EF24 analogs targeting IKKbeta were
      designed and synthesized. Several IKKbeta inhibitors with better activities than
      EF24 were screened out and B3 showed best IKKbeta inhibitory (IC50: 6.6 MUM).
      Molecular docking and dynamic simulation experiments further confirmed this
      inhibitory effect. B3 obviously suppressed the viability of Hela229, A549, SGC
      7901 and MGC-803 cells. Then, in SGC-7901 and MGC-803 cells, B3 blocked the NF
      kappaB signal pathway by inhibiting IKKbeta phosphorylation, and followed
      arrested the cell cycle at G2/M phase by suppressing the Cyclin B1 and Cdc2 p34
      expression, induced the cell apoptosis by down-regulating Bcl-2 protein and up
      regulating cleaved-caspase3. Moreover, B3 significantly reduced tumor growth and
      suppressed the IKKbeta-NF-kappaB signal pathway in SGC-7901 xenograft model. In
      total, this study present a potential IKKbeta inhibitor as anti-tumor precursor.

PMID- 29351888
TI  - Distribution and availability of mercury and methylmercury in different waters
      from the Rio Madeira Basin, Amazon.
AB  - Waters from the Amazon Basin have distinct physicochemical characteristics that
      can be optically classified as "black", "clear" and "white". We studied the
      distribution of total-Hg (THg) and methyl-Hg (MeHg) in these waters and
      respective suspended solids, sediment, phytoplankton, zooplankton, and benthic
      macroinvertebrates (BM) in the Madeira River Basin. Compared with the other types
      of water, the more acidic "black" kind had the highest THg and MeHg
      concentrations. The trend (black > clear > white) occurred for the concentrations
      of THg and MeHg in sediments and in the biotic compartment (plankton,
      macroinvertebrates). Organic Hg accounted for a small percentage (0.6-0.4%) of
      the THg in sediments but was highest in water (17-15%). For plankton and BM, the
      biota sediment accumulation factor (BSAFs) of MeHg (53-125) were greater than
      those of THg (4.5-15); however, the BSAF trend according to water type (black >
      clear > white) was only significant for MeHg. Sediment THg is correlated with all
      forms of Hg in biotic and abiotic matrices. The results indicate that water
      acidity in the Amazon is an important chemical characteristic in assessing Hg
      contamination of sediments and bioaccumulation in the aquatic food web. The
      differences in the BSAFs between THg and MeHg support the use of this factor for
      evaluating the bioaccumulation potential of sediment-bound Hg. The results add
      information critical to assessing environmental and health risks related to Hg
      methylation and potential fish-MeHg contamination, especially in tropical aquatic
      environments.

PMID- 29351890
TI  - Evolutionary mechanisms studied through protein fitness landscapes.
AB  - Biology has, and continues to be, shaped by evolutionary mechanisms. Within the
      past decade, local fitness landscapes have become experimentally tractable and
      are providing new perspectives on evolutionary mechanisms. Powered by next
      generation sequencing, the impacts of all individual amino acid substitutions on
      function have been quantified for dozens of proteins. These fitness maps have
      been utilized to investigate the biophysical underpinnings of existing protein
      function as well as the appearance and enhancement of new protein functions. This
      review highlights emerging trends from this rapidly growing area of research,
      including an expanded understanding of the biophysical mechanisms underlying
      existing and new protein function, the roles epistasis and adaptation play in
      shaping evolution, and the prediction of disease-causing alleles in humans.

PMID- 29351889
TI  - Disentangling the effects of low pH and metal mixture toxicity on
      macroinvertebrate diversity.
AB  - One of the primary goals of biological assessment of streams is to identify which
      of a suite of chemical stressors is limiting their ecological potential. Elevated
      metal concentrations in streams are often associated with low pH, yet the effects
      of these two potentially limiting factors of freshwater biodiversity are rarely
      considered to interact beyond the effects of pH on metal speciation. Using a
      dataset from two continents, a biogeochemical model of the toxicity of metal
      mixtures (Al, Cd, Cu, Pb, Zn) and quantile regression, we addressed the relative
      importance of both pH and metals as limiting factors for macroinvertebrate
      communities. Current environmental quality standards for metals proved to be
      protective of stream macroinvertebrate communities and were used as a starting
      point to assess metal mixture toxicity. A model of metal mixture toxicity
      accounting for metal interactions was a better predictor of macroinvertebrate
      responses than a model considering individual metal toxicity. We showed that the
      direct limiting effect of pH on richness was of the same magnitude as that of
      chronic metal toxicity, independent of its influence on the availability and
      toxicity of metals. By accounting for the direct effect of pH on
      macroinvertebrate communities, we were able to determine that acidic streams
      supported less diverse communities than neutral streams even when metals were
      below no-effect thresholds. Through a multivariate quantile model, we untangled
      the limiting effect of both pH and metals and predicted the maximum diversity
      that could be expected at other sites as a function of these variables. This
      model can be used to identify which of the two stressors is more limiting to the
      ecological potential of running waters.

PMID- 29351891
TI  - Overexpression of a wheat (Triticum aestivum L.) bZIP transcription factor gene,
      TabZIP6, decreased the freezing tolerance of transgenic Arabidopsis seedlings by
      down-regulating the expression of CBFs.
AB  - The basic leucine zipper (bZIP) proteins play important roles against abiotic
      stress in plants, including cold stress. However, most bZIPs involved in plant
      freezing tolerance are positive regulators. Only a few bZIPs function negatively
      in cold stress response. In this study, TabZIP6, a Group C bZIP transcription
      factor gene from common wheat (Triticum aestivum L.), was cloned and
      characterized. The transcript of TabZIP6 was strongly induced by cold treatment
      (4  degrees C). TabZIP6 is a nuclear-localized protein with transcriptional
      activation activity. Arabidopsis plants overexpressing TabZIP6 showed decreased
      tolerance to freezing stress. Microarray as well as quantitative real-time PCR
      (qRT-PCR) analysis showed that CBFs and some key COR genes, including COR47 and
      COR15B, were down-regulated by cold treatment in TabZIP6-overexpressing
      Arabidopsis lines. TabZIP6 was capable of binding to the G-box motif and the CBF1
      and CBF3 promoters in yeast cells. A yeast two-hybrid assay revealed that
      TabZIP6, as well as the other two Group S bZIP proteins involved in cold stress
      tolerance in wheat, Wlip19 and TaOBF1, can form homodimers by themselves and
      heterodimers with each other. These results suggest that TabZIP6 may function
      negatively in the cold stress response by binding to the promoters of CBFs, and
      thereby decreasing the expression of downstream COR genes in TabZIP6
      overexpressing Arabidopsis seedlings.

PMID- 29351892
TI  - Identification and functional analysis of cassava DELLA proteins in plant disease
      resistance against cassava bacterial blight.
AB  - Gibberellin (GA) is an essential plant hormone in plant growth and development as
      well as various stress responses. DELLA proteins are important repressors of GA
      signal pathway. GA and DELLA have been extensively investigated in several model
      plants. However, the in vivo roles of GA and DELLA in cassava, one of the most
      important crops and energy crops in the tropical area, are unknown. In this
      study, systematic genome-wide analysis identified 4 MeDELLAs in cassava, as
      evidenced by the evolutionary tree, gene structures and motifs analyses. Gene
      expression analysis found that 4 MeDELLAs were commonly regulated by flg22 and
      Xanthomonas axonopodis pv manihotis (Xam). Through overexpression in Nicotiana
      benthamiana, we found that 4 MeDELLAs conferred improved disease resistance
      against cassava bacterial blight. Through virus-induced gene silencing (VIGS) in
      cassava, we found that MeDELLA-silenced plants exhibited decreased disease
      resistance, with less callose deposition and lower transcript levels of defense
      related genes. This is the first study identifying MeDELLAs as positive
      regulators of disease resistance against cassava bacterial blight.

PMID- 29351893
TI  - A Clinical Decision Support Engine Based on a National Medication Repository for
      the Detection of Potential Duplicate Medications: Design and Evaluation.
AB  - BACKGROUND: A computerized physician order entry (CPOE) system combined with a
      clinical decision support system can reduce duplication of medications and thus
      adverse drug reactions. However, without infrastructure that supports patients'
      integrated medication history across health care facilities nationwide,
      duplication of medication can still occur. In Taiwan, the National Health
      Insurance Administration has implemented a national medication repository and Web
      based query system known as the PharmaCloud, which allows physicians to access
      their patients' medication records prescribed by different health care facilities
      across Taiwan. OBJECTIVE: This study aimed to develop a scalable, flexible, and
      thematic design-based clinical decision support (CDS) engine, which integrates a
      national medication repository to support CPOE systems in the detection of
      potential duplication of medication across health care facilities, as well as to
      analyze its impact on clinical encounters. METHODS: A CDS engine was developed
      that can download patients' up-to-date medication history from the PharmaCloud
      and support a CPOE system in the detection of potential duplicate medications.
      When prescribing a medication order using the CPOE system, a physician receives
      an alert if there is a potential duplicate medication. To investigate the impact
      of the CDS engine on clinical encounters in outpatient services, a clinical
      encounter log was created to collect information about time, prescribed drugs,
      and physicians' responses to handling the alerts for each encounter. RESULTS: The
      CDS engine was installed in a teaching affiliate hospital, and the clinical
      encounter log collected information for 3 months, during which a total of 178,300
      prescriptions were prescribed in the outpatient departments. In all,
      43,844/178,300 (24.59%) patients signed the PharmaCloud consent form allowing
      their physicians to access their medication history in the PharmaCloud. The rate
      of duplicate medication was 5.83% (1843/31,614) of prescriptions. When
      prescribing using the CDS engine, the median encounter time was 4.3 (IQR 2.3-7.3)
      min, longer than that without using the CDS engine (median 3.6, IQR 2.0-6.3 min).
      From the physicians' responses, we found that 42.06% (1908/4536) of the potential
      duplicate medications were recognized by the physicians and the medication orders
      were canceled. CONCLUSIONS: The CDS engine could easily extend functions for
      detection of adverse drug reactions when more and more electronic health record
      systems are adopted. Moreover, the CDS engine can retrieve more updated and
      completed medication histories in the PharmaCloud, so it can have better
      performance for detection of duplicate medications. Although our CDS engine
      approach could enhance medication safety, it would make for a longer encounter
      time. This problem can be mitigated by careful evaluation of adopted solutions
      for implementation of the CDS engine. The successful key component of a CDS
      engine is the completeness of the patient's medication history, thus further
      research to assess the factors in increasing the PharmaCloud consent rate is
      required.

PMID- 29351894
TI  - The Use of Technology in Identifying Hospital Malnutrition: Scoping Review.
AB  - BACKGROUND: Malnutrition is a condition most commonly arising from the inadequate
      consumption of nutrients necessary to maintain physiological health and is
      associated with the development of cardiovascular disease, osteoporosis, and
      sarcopenia. Malnutrition occurring in the hospital setting is caused by
      insufficient monitoring, identification, and assessment efforts. Furthermore, the
      ability of health care workers to identify and recognize malnourished patients is
      suboptimal. Therefore, interventions focusing on the identification and treatment
      of malnutrition are valuable, as they reduce the risks and rates of malnutrition
      within hospitals. Technology may be a particularly useful ally in identifying
      malnutrition due to scalability, timeliness, and effectiveness. In an effort to
      explore the issue, this scoping review synthesized the availability of
      technological tools to detect and identify hospital malnutrition. OBJECTIVE: Our
      objective was to conduct a scoping review of the different forms of technology
      used in addressing malnutrition among adults admitted to hospital to (1) identify
      the extent of the published literature on this topic, (2) describe key findings,
      and (3) identify outcomes. METHODS: We designed and implemented a search strategy
      in 3 databases (PubMed, Scopus, and CINAHL). We completed a descriptive numerical
      summary and analyzed study characteristics. One reviewer independently extracted
      data from the databases. RESULTS: We retrieved and reviewed a total of 21
      articles. We categorized articles by the computerized tool or app type:
      malnutrition assessment (n=15), food intake monitoring (n=5), or both (n=1).
      Within those categories, we subcategorized the different technologies as either
      hardware (n=4), software (n=13), or both (n=4). An additional subcategory under
      software was cloud-based apps (n=1). Malnutrition in the acute hospital setting
      was largely an unrecognized problem, owing to insufficient monitoring,
      identification, and initial assessments of identifying both patients who are
      already malnourished and those who are at risk of malnourishment. Studies went on
      to examine the effectiveness of health care workers (nurses and doctors) with a
      knowledge base focused on clinical care and their ability to accurately and
      consistently identify malnourished geriatric patients within that setting.
      CONCLUSIONS: Most articles reported effectiveness in accurately increasing
      malnutrition detection and awareness. Computerized tools and apps may also help
      reduce health care workers' workload and time spent assessing patients for
      malnutrition. Hospitals may also benefit from implementing malnutrition
      technology through observing decreased length of stay, along with decreased
      foregone costs related to missing malnutrition diagnoses. It is beneficial to
      study the impact of these technologies to examine possible areas of improvement.
      A future systematic review would further contribute to the evidence and
      effectiveness of the use of technologies in assessing and monitoring hospital
      malnutrition.

PMID- 29351895
TI  - A Tailored Web-Based Intervention to Improve Parenting Risk and Protective
      Factors for Adolescent Depression and Anxiety Problems: Postintervention Findings
      From a Randomized Controlled Trial.
AB  - BACKGROUND: Depression and anxiety disorders in young people are a global health
      concern. Parents have an important role in reducing the risk of these disorders,
      but cost-effective, evidence-based interventions for parents that can be widely
      disseminated are lacking. OBJECTIVE: This study aimed to examine the
      postintervention effects of the Partners in Parenting (PiP) program on parenting
      risk and protective factors for adolescent depression and anxiety, and on
      adolescent depression and anxiety symptoms. METHODS: A two-arm randomized
      controlled trial was conducted with 359 parent-adolescent dyads, recruited
      primarily through schools across Australia. Parents and adolescents were assessed
      at baseline and 3 months later (postintervention). Parents in the intervention
      condition received PiP, a tailored Web-based parenting intervention designed
      following Persuasive Systems Design (PSD) principles to target parenting factors
      associated with adolescents' risk for depression and anxiety problems. PiP
      comprises a tailored feedback report highlighting each parent's strengths and
      areas for improvement, followed by a set of interactive modules (up to nine) that
      is specifically recommended for the parent based on individually identified areas
      for improvement. Parents in the active-control condition received a standardized
      package of five Web-based factsheets about adolescent development and well-being.
      Parents in both conditions received a 5-min weekly call to encourage progress
      through their allocated program to completion. Both programs were delivered
      weekly via the trial website. The primary outcome measure at postintervention was
      parent-reported changes in parenting risk and protective factors, which were
      measured using the Parenting to Reduce Adolescent Depression and Anxiety Scale
      (PRADAS). Secondary outcome measures were the adolescent-report PRADAS, the
      parent- and child-report Short Mood and Feelings Questionnaire (depressive
      symptoms), and parent- and child-report Spence Children's Anxiety Scale (anxiety
      symptoms). RESULTS: Parents in the intervention condition completed a mean of
      73.7% of their intended personalized PiP program. A total of 318 parents (88.6%,
      318/359) and 308 adolescents (92.8%, 308/332) completed the postintervention
      assessment. Attrition was handled using mixed model of repeated measures analysis
      of variance. As hypothesized, we found a significant condition-by-time
      interaction on the PRADAS, with a medium effect size, Cohen d=0.57, 95% CI 0.34
      0.79. No significant differences between conditions were found at
      postintervention on any of the secondary outcome measures, with adolescent
      depressive (parent-report only) and anxiety (both parent- and adolescent-report)
      symptoms decreasing significantly from baseline to postintervention in both
      conditions. CONCLUSIONS: The fully automated PiP intervention showed promising
      short-term effects on parenting behaviors that are associated with adolescents'
      risk for depression and anxiety. Long-term follow-up is required to ascertain
      whether these effects translate into reduced adolescent depression and anxiety
      problems. The intervention may be useful as a low-cost universal public health
      program to increase parenting practices believed to benefit adolescents' mental
      health. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry:
      ACTRN12615000328572; https://www.anzctr.org.au/
      Trial/Registration/TrialReview.aspx? id=368274 (Archived by WebCite at
      http://www.webcitation.org/6qgsZ3Aqj).

PMID- 29351896
TI  - Internet Exposure Associated With Canadian Parents' Perception of Risk on
      Childhood Immunization: Cross-Sectional Study.
AB  - BACKGROUND: There is a large presence of provaccination and antivaccination
      content on the Internet. The Internet has been identified as an important source
      for parents to seek and share vaccine information. There are concerns that
      parental fears or hesitancy on childhood immunizations are increasing due to the
      popularity of social media and exposure to online antivaccination sentiment. No
      other studies have investigated the association between seeking vaccine
      information online and Canadian parents' perception of risk on childhood
      immunization. OBJECTIVE: We aimed to investigate the potential association
      between seeking vaccine information on the Internet and Canadian parents'
      perception of risk on childhood immunization in order to quantify the perceived
      association and increase our understanding on the impact of the Internet to help
      guide public health interventions. METHODS: We analyzed this association in two
      population samples: a self-selecting Web-based sample of Canadian parents
      recruited through Facebook (n=966) and a population-based sample of parents
      recruited by random digit dialing (RDD; n=951). The outcome was parental
      perception of vaccine safety on a seven-point ordinal scale from "not safe" to
      "extremely safe." An ordinal regression model was used to investigate if Internet
      information seeking on childhood vaccination predicted parental perception of
      vaccine safety. RESULTS: After adjusting for income level, Internet reliability,
      age of parent, and region, the odds of perceiving vaccines as less safe rather
      than more safe were 1.6 times higher (95% CI 1.3-2.1) for parents who used the
      Internet to search for vaccination information compared to parents who did not
      search the Internet in the Web-based sample, and 2.0 times higher (95% CI 1.6
      2.5) in the population-based RDD sample. CONCLUSIONS: The results suggest the
      Internet is significantly associated with Canadian parents' negative perception
      of vaccine risk. Governmental and scientific sectors should consider the
      development and implementation of Web-based vaccine interventions to promote
      confidence in immunization.

PMID- 29351898
TI  - Young People's, Parents', and Professionals' Views on Required Components of
      Mobile Apps to Support Self-Management of Juvenile Arthritis: Qualitative Study.
AB  - BACKGROUND: There is growing evidence that supporting self-management of Juvenile
      Arthritis can benefit both patients and professionals. Young people with Juvenile
      Arthritis and their healthy peers increasingly use mobile technologies to access
      information and support in day-to-day life. Therefore, a user-led, rigorously
      developed and evaluated mobile app could be valuable for facilitating young
      people's self-management of Juvenile Arthritis. OBJECTIVE: The objective of this
      study was to seek the views of young people with Juvenile Arthritis, their
      parents or carers, and health care professionals (HCPs) as to what should be
      included in a mobile app to facilitate young people's self-management of chronic
      Juvenile Arthritis. METHODS: A qualitative approach was adopted with a purposeful
      sample of 9 young people aged 10-18 years with Juvenile Arthritis, 8 parents or
      carers, and 8 HCPs involved in their care. Data were gathered through semi
      structured focus group and individual interviews with young people and their
      parents or carers and HCPs. Interview discussion was facilitated through
      demonstration of four existing health apps to explore participants' views on
      strengths and limitations of these, barriers and facilitators to mobile app use,
      preferred designs, functionality, levels of interaction, and data sharing
      arrangements. Data were analyzed using the framework approach. RESULTS: Analysis
      revealed three interlinked, overarching themes: (1) purpose, (2) components and
      content, and (3) social support. Despite some differences in emphasis on
      essential content, general agreement was found between young people with Juvenile
      Arthritis their parents or carers, and professionals that a mobile app to aid
      self-management would be useful. Underpinning the themes was a prerequisite that
      young people are enabled to feel a sense of ownership and control of the app, and
      that it be an interactive, engaging resource that offers developmentally
      appropriate information and reminders, as well as enabling them to monitor their
      symptoms and access social support. CONCLUSIONS: Findings justify and pave the
      way for a future feasibility study into the production and preliminary testing of
      such an app. This would consider issues such as compatibility with existing
      technologies, costs, age, and cross-gender appeal as well as resource
      implications.

PMID- 29351897
TI  - Transitions Between Circulatory States After Out-of-Hospital Cardiac Arrest:
      Protocol for an Observational, Prospective Cohort Study.
AB  - BACKGROUND: The post cardiac arrest syndrome (PCAS) is responsible for the
      majority of in-hospital deaths following cardiac arrest (CA). The major elements
      of PCAS are anoxic brain injury and circulatory failure. OBJECTIVE: This study
      aimed to investigate the clinical characteristics of circulatory failure and
      inflammatory responses after out-of-hospital cardiac arrest (OHCA) and to
      identify patterns of circulatory and inflammatory responses, which may predict
      circulatory deterioration in PCAS. METHODS: This study is a single-center cohort
      study of 50 patients who receive intensive care after OHCA. The patients are
      followed for 5 days where detailed information from circulatory variables,
      including measurements by pulmonary artery catheters (PACs), is obtained in high
      resolution. Blood samples for inflammatory and endothelial biomarkers are taken
      at inclusion and thereafter daily. Every 10 min, the patients will be assessed
      and categorized in one of three circulatory categories. These categories are
      based on mean arterial pressure; heart rate; serum lactate concentrations;
      superior vena cava oxygen saturation; and need for fluid, vasoactive medications,
      and other interventions. We will analyze predictors of circulatory failure and
      their relation to inflammatory biomarkers. RESULTS: Patient inclusion started in
      January 2016. CONCLUSIONS: This study will obtain advanced hemodynamic data with
      high resolution during the acute phase of PCAS and will analyze the details in
      circulatory state transitions related to circulatory failure. We aim to identify
      early predictors of circulatory deterioration and favorable outcome after CA.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT02648061;
      https://clinicaltrials.gov/ct2/show/NCT02648061 (Archived by WebCite at
      http://www.webcitation.org/6wVASuOla).

PMID- 29351899
TI  - Web-Based Survey Application to Collect Contextually Relevant Geographic Data
      With Exposure Times: Application Development and Feasibility Testing.
AB  - BACKGROUND: Although studies that characterize the risk environment by linking
      contextual factors with individual-level data have advanced infectious disease
      and substance use research, there are opportunities to refine how we define
      relevant neighborhood exposures; this can in turn reduce the potential for
      exposure misclassification. For example, for those who do not inject at home,
      injection risk behaviors may be more influenced by the environment where they
      inject than where they live. Similarly, among those who spend more time away from
      home, a measure that accounts for different neighborhood exposures by weighting
      each unique location proportional to the percentage of time spent there may be
      more correlated with health behaviors than one's residential environment.
      OBJECTIVE: This study aimed to develop a Web-based application that interacts
      with Google Maps application program interfaces (APIs) to collect contextually
      relevant locations and the amount of time spent in each. Our analysis examined
      the extent of overlap across different location types and compared different
      approaches for classifying neighborhood exposure. METHODS: Between May 2014 and
      March 2017, 547 participants enrolled in a Baltimore HIV care and prevention
      study completed an interviewer-administered Web-based survey that collected
      information about where participants were recruited, worked, lived, socialized,
      injected drugs, and spent most of their time. For each location, participants
      gave an address or intersection which they confirmed using Google Map and Street
      views. Geographic coordinates (and hours spent in each location) were joined to
      neighborhood indicators by Community Statistical Area (CSA). We computed a
      weighted exposure based on the proportion of time spent in each unique location.
      We compared neighborhood exposures based on each of the different location types
      with one another and the weighted exposure using analysis of variance with
      Bonferroni corrections to account for multiple comparisons. RESULTS: Participants
      reported spending the most time at home, followed by the location where they
      injected drugs. Injection locations overlapped most frequently with locations
      where people reported socializing and living or sleeping. The least time was
      spent in the locations where participants reported earning money and being
      recruited for the study; these locations were also the least likely to overlap
      with other location types. We observed statistically significant differences in
      neighborhood exposures according to the approach used. Overall, people reported
      earning money in higher-income neighborhoods and being recruited for the study
      and injecting in neighborhoods with more violent crime, abandoned houses, and
      poverty. CONCLUSIONS: This analysis revealed statistically significant
      differences in neighborhood exposures when defined by different locations or
      weighted based on exposure time. Future analyses are needed to determine which
      exposure measures are most strongly associated with health and risk behaviors and
      to explore whether associations between individual-level behaviors and
      neighborhood exposures are modified by exposure times.

PMID- 29351900
TI  - Employees' Perspectives on the Facilitators and Barriers to Engaging With Digital
      Mental Health Interventions in the Workplace: Qualitative Study.
AB  - BACKGROUND: Prevalence rates of work-related stress, depression, and anxiety are
      high, resulting in reduced productivity and increased absenteeism. There is
      evidence that these conditions can be successfully treated in the workplace, but
      take-up of psychological treatments among workers is low. Digital mental health
      interventions delivered in the workplace may be one way to address this
      imbalance, but although there is evidence that digital mental health is effective
      at treating stress, depression, and anxiety in the workplace, uptake of and
      engagement with these interventions remains a concern. Additionally, there is
      little research on the appropriateness of the workplace for delivering these
      interventions or on what the facilitators and barriers to engagement with digital
      mental health interventions in an occupational setting might be. OBJECTIVE: The
      aim of this research was to get a better understanding of the facilitators and
      barriers to engaging with digital mental health interventions in the workplace.
      METHODS: Semistructured interviews were held with 18 participants who had access
      to an occupational digital mental health intervention as part of a randomized
      controlled trial. The interviews were transcribed, and thematic analysis was used
      to develop an understanding of the data. RESULTS: Digital mental health
      interventions were described by interviewees as convenient, flexible, and
      anonymous; these attributes were seen as being both facilitators and barriers to
      engagement in a workplace setting. Convenience and flexibility could increase the
      opportunities to engage with digital mental health, but in a workplace setting
      they could also result in difficulty in prioritizing time and ensuring a temporal
      and spatial separation between work and therapy. The anonymity of the Internet
      could encourage use, but that benefit may be lost for people who work in open
      plan offices. Other facilitators to engagement included interactive and
      interesting content and design features such as progress trackers and reminders
      to log in. The main barrier to engagement was the lack of time. The perfect
      digital mental health intervention was described as a website that combined a
      short interactive course that was accessed alongside time-unlimited information
      and advice that was regularly updated and could be dipped in and out of.
      Participants also wanted access to e-coaching support. CONCLUSIONS: Occupational
      digital mental health interventions may have an important role in delivering
      health care support to employees. Although the advantages of digital mental
      health interventions are clear, they do not always fully translate to
      interventions delivered in an occupational setting and further work is required
      to identify ways of minimizing potential barriers to access and engagement. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02729987;
      https://clinicaltrials.gov/ct2/show/NCT02729987?term=NCT02729987& rank=1
      (Archived at WebCite at http://www.webcitation.org/6wZJge9rt).

PMID- 29351901
TI  - XIAP Regulation by MNK Links MAPK and NFkappaB Signaling to Determine an
      Aggressive Breast Cancer Phenotype.
AB  - Hyperactivation of the NFkappaB pathway is a distinct feature of inflammatory
      breast cancer (IBC), a highly proliferative and lethal disease. Gene expression
      studies in IBC patient tissue have linked EGFR (EGFR/HER2)-mediated MAPK
      signaling to NFkappaB hyperactivity, but the mechanism(s) by which this occurs
      remain unclear. Here, we report that the X-linked inhibitor of apoptosis protein
      (XIAP) plays a central role in linking these two pathways. XIAP overexpression
      correlated with poor prognoses in breast cancer patients and was frequently
      observed in untreated IBC patient primary tumors. XIAP drove constitutive
      NFkappaB transcriptional activity, which mediated ALDH positivity (a marker of
      stem-like cells), in vivo tumor growth, and an IBC expression signature in
      patient-derived IBC cells. Using pathway inhibitors and mathematical models, we
      defined a new role for the MAPK interacting (Ser/Thr)-kinase (MNK) in enhancing
      XIAP expression and downstream NFkappaB signaling. Furthermore, targeted XIAP
      knockdown and treatment with a MNK inhibitor decreased tumor cell migration in a
      dorsal skin fold window chamber murine model that allowed for intravital imaging
      of local tumor growth and migration. Together, our results indicate a novel role
      for XIAP in the molecular cross-talk between MAPK and NFkappaB pathways in
      aggressive tumor growth, which has the potential to be therapeutically
      exploited.Significance: Signaling by the MNK kinase is essential in inflammatory
      breast cancer, and it can be targeted to inhibit XIAP-NFkappaB signaling and the
      aggressive phenotype of this malignancy. Cancer Res; 78(7); 1726-38. (c)2018
      AACR.

PMID- 29351902
TI  - Targeting the SphK1/S1P/S1PR1 Axis That Links Obesity, Chronic Inflammation, and
      Breast Cancer Metastasis.
AB  - Although obesity with associated inflammation is now recognized as a risk factor
      for breast cancer and distant metastases, the functional basis for these
      connections remain poorly understood. Here, we show that in breast cancer
      patients and in animal breast cancer models, obesity is a sufficient cause for
      increased expression of the bioactive sphingolipid mediator sphingosine-1
      phosphate (S1P), which mediates cancer pathogenesis. A high-fat diet was
      sufficient to upregulate expression of sphingosine kinase 1 (SphK1), the enzyme
      that produces S1P, along with its receptor S1PR1 in syngeneic and spontaneous
      breast tumors. Targeting the SphK1/S1P/S1PR1 axis with FTY720/fingolimod
      attenuated key proinflammatory cytokines, macrophage infiltration, and tumor
      progression induced by obesity. S1P produced in the lung premetastatic niche by
      tumor-induced SphK1 increased macrophage recruitment into the lung and induced
      IL6 and signaling pathways important for lung metastatic colonization.
      Conversely, FTY720 suppressed IL6, macrophage infiltration, and S1P-mediated
      signaling pathways in the lung induced by a high-fat diet, and it dramatically
      reduced formation of metastatic foci. In tumor-bearing mice, FTY720 similarly
      reduced obesity-related inflammation, S1P signaling, and pulmonary metastasis,
      thereby prolonging survival. Taken together, our results establish a critical
      role for circulating S1P produced by tumors and the SphK1/S1P/S1PR1 axis in
      obesity-related inflammation, formation of lung metastatic niches, and breast
      cancer metastasis, with potential implications for prevention and
      treatment.Significance: These findings offer a preclinical proof of concept that
      signaling by a sphingolipid may be an effective target to prevent obesity-related
      breast cancer metastasis. Cancer Res; 78(7); 1713-25. (c)2018 AACR.

PMID- 29351903
TI  - Integrative Genomic Analysis Predicts Causative Cis-Regulatory Mechanisms of the
      Breast Cancer-Associated Genetic Variant rs4415084.
AB  - Previous genome-wide association studies (GWAS) have identified several common
      genetic variants that may significantly modulate cancer susceptibility. However,
      the precise molecular mechanisms behind these associations remain largely
      unknown; it is often not clear whether discovered variants are themselves
      functional or merely genetically linked to other functional variants. Here, we
      provide an integrated method for identifying functional regulatory variants
      associated with cancer and their target genes by combining analyses of expression
      quantitative trait loci, a modified version of allele-specific expression that
      systematically utilizes haplotype information, transcription factor (TF)-binding
      preference, and epigenetic information. Application of our method to a breast
      cancer susceptibility region in 5p12 demonstrates that the risk allele rs4415084
      T correlates with higher expression levels of the protein-coding gene
      mitochondrial ribosomal protein S30 (MRPS30) and lncRNA RP11-53O19.1 We propose
      an intergenic SNP rs4321755, in linkage disequilibrium (LD) with the GWAS SNP
      rs4415084 (r2 = 0.988), to be the predicted functional SNP. The risk allele
      rs4321755-T, in phase with the GWAS rs4415084-T, created a GATA3-binding motif
      within an enhancer, resulting in differential GATA3 binding and chromatin
      accessibility, thereby promoting transcription of MRPS30 and RP11-53O19.1. MRPS30
      encodes a member of the mitochondrial ribosomal proteins, implicating the role of
      risk SNP in modulating mitochondrial activities in breast cancer. Our
      computational framework provides an effective means to integrate GWAS results
      with high-throughput genomic and epigenomic data and can be extended to
      facilitate rapid functional characterization of other genetic variants modulating
      cancer susceptibility.Significance: Unification of GWAS results with information
      from high-throughput genomic and epigenomic profiles provides a direct link
      between common genetic variants and measurable molecular perturbations. Cancer
      Res; 78(7); 1579-91. (c)2018 AACR.

PMID- 29351904
TI  - ERalpha-Mediated Nuclear Sequestration of RSK2 Is Required for ER+ Breast Cancer
      Tumorigenesis.
AB  - Although ribosomal protein S6 kinase A3 (RSK2) activation status positively
      correlates with patient responses to antiestrogen hormonal therapies, the
      mechanistic basis for these observations is unknown. Using multiple in vitro and
      in vivo models of estrogen receptor-positive (ER+) breast cancer, we report that
      ERalpha sequesters active RSK2 into the nucleus to promote neoplastic
      transformation and facilitate metastatic tumor growth. RSK2 physically interacted
      with ERalpha through its N terminus to activate a proneoplastic transcriptional
      network critical to the ER+ lineage in the mammary gland, thereby providing a
      gene signature that effectively stratified patient tumors according to ERalpha
      status. ER+ tumor growth was strongly dependent on nuclear RSK2, and transgenic
      mice engineered to stably express nuclear RSK2 in the mammary gland developed
      high-grade ductal carcinoma in situ Mammary cells isolated from the transgenic
      model and introduced systemically successfully disseminated and established
      metastatic lesions. Antiestrogens disrupted the interaction between RSK2 and
      ERalpha, driving RSK2 into the cytoplasm and impairing tumor formation. These
      findings establish RSK2 as an obligate participant of ERalpha-mediated
      transcriptional programs, tumorigenesis, and divergent patient responses to
      antiestrogen therapies.Significance: Nuclear accumulation of active RSK drives a
      protumorigenic transcriptional program and renders ER+ breast cancer susceptible
      to endocrine-based therapies. Cancer Res; 78(8); 2014-25. (c)2018 AACR.

PMID- 29351905
TI  - Cancer treatment in childhood and testicular function: the importance of the
      somatic environment.
AB  - Testicular function and future fertility may be affected by cancer treatment
      during childhood. Whilst survival of the germ (stem) cells is critical for
      ensuring the potential for fertility in these patients, the somatic cell
      populations also play a crucial role in providing a suitable environment to
      support germ cell maintenance and subsequent development. Regulation of the
      spermatogonial germ-stem cell niche involves many signalling pathways with
      hormonal influence from the hypothalamo-pituitary-gonadal axis. In this review,
      we describe the somatic cell populations that comprise the testicular germ-stem
      cell niche in humans and how they may be affected by cancer treatment during
      childhood. We also discuss the experimental models that may be utilized to
      manipulate the somatic environment and report the results of studies that
      investigate the potential role of somatic cells in the protection of the germ
      cells in the testis from cancer treatment.

PMID- 29351906
TI  - EDC IMPACT: Molecular effects of developmental FM 550 exposure in Wistar rat
      placenta and fetal forebrain.
AB  - Firemaster 550 (FM 550) is a flame retardant (FR) mixture that has become one of
      the most commonly used FRs in foam-based furniture and baby products. Human
      exposure to this commercial mixture, composed of brominated and organophosphate
      components, is widespread. We have repeatedly shown that developmental exposure
      can lead to sex-specific behavioral effects in rats. Accruing evidence of
      endocrine disruption and potential neurotoxicity has raised concerns regarding
      the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of
      action remains unclear. Additionally, we observed significant, and in some cases
      sex-specific, accumulation of FM 550 in placental tissue following gestational
      exposure. Because the placenta is an important source of hormones and
      neurotransmitters for the developing brain, it may be a critical target of
      toxicity to consider in the context of developmental neurotoxicity. Using a
      mixture of targeted and exploratory approaches, the goal of the present study was
      to identify possible mechanisms of action in the developing forebrain and
      placenta. Wistar rat dams were orally exposed to FM 550 (0, 300 or 1000 ug/day)
      for 10 days during gestation and placenta and fetal forebrain tissue collected
      for analysis. In placenta, evidence of endocrine, inflammatory and
      neurotransmitter signaling pathway disruption was identified. Notably, 5-HT
      turnover was reduced in placental tissue and fetal forebrains indicating that 5
      HT signaling between the placenta and the embryonic brain may be disrupted. These
      findings demonstrate that environmental contaminants, like FM 550, have the
      potential to impact the developing brain by disrupting normal placental
      functions.

PMID- 29351907
TI  - Energy Connections and Misconnections across Chemistry and Biology.
AB  - Despite the number of university students who take courses in multiple science
      disciplines, little is known about how they connect concepts between disciplines.
      Energy is a concept that underlies all scientific phenomena and, as such,
      provides an appropriate context in which to investigate student connections and
      misconnections across disciplines. In this study, university students
      concurrently enrolled in introductory chemistry and biology were interviewed to
      explore their perceptions of the integration of energy both within and across the
      disciplines, and how they attempted to accommodate and reconcile different
      disciplinary approaches to energy, to inform future, interdisciplinary course
      reform. Findings suggest that, while students believed energy to be important to
      the scientific world and to the disciplines of biology and chemistry, the extent
      to which it was seen as central to success in their courses varied. Differences
      were also apparent in students' descriptions of the molecular-level mechanisms by
      which energy transfer occurs. These findings reveal a disconnect between how
      energy is understood and used in introductory science course work and uncovers
      opportunities to make stronger connections across the disciplines. We recommend
      that instructors engage in interdisciplinary conversations and consider the
      perspectives and goals of other disciplines when teaching introductory science
      courses.

PMID- 29351908
TI  - Enhancing Conceptual Knowledge of Energy in Biology with Incorrect
      Representations.
AB  - Energy is an important concept in all natural sciences, and a challenging one for
      school science education. Students' conceptual knowledge of energy is often low,
      and they entertain misconceptions. Educational research in science and
      mathematics suggests that learning through depictive representations and learning
      from errors, based on the theory of negative knowledge, can potentially foster
      students' knowledge of abstract concepts such as energy. Thus, we propose here an
      instructional approach that combines these two strategies to foster conceptual
      knowledge of energy. It involves inserting an error in a biological energy flow
      diagram, an error that we derived from two prevalent misconceptions about energy:
      1) plants get some of their energy from the soil or 2) energy cycles in an
      ecosystem. The approach's effect on students' conceptual knowledge of energy was
      tested in an intervention study with pre-post design and 304 ninth grade students
      (M = 14.79 years). Students who successfully identified and explained the error
      achieved larger gains in conceptual knowledge than students learning with a
      correct diagram. Thus, the proposed instructional approach holds promise for
      improving energy teaching.

PMID- 29351909
TI  - Arrows in Biology: Lack of Clarity and Consistency Points to Confusion for
      Learners.
AB  - In this article, we begin to unpack the phenomenon of representational competence
      by exploring how arrow symbols are used in introductory biology textbook figures.
      Out of 1214 figures in an introductory biology textbook, 632 (52%) of them
      contained arrows that were used to represent many different concepts or
      processes. Analysis of these figures revealed little correlation between arrow
      style and meaning. A more focused study of 86 figures containing 230 arrows from
      a second textbook showed the same pattern of inconsistency. Interviews with
      undergraduates confirmed that arrows in selected textbook figures were confusing
      and did not readily convey the information intended by the authors. We also
      present findings from an online survey in which subjects were asked to infer
      meaning of different styles of arrows in the absence of context. Few arrow styles
      had intrinsic meaning to participants, and illustrators did not always use those
      arrows for the meanings expected by students. Thus, certain styles of arrows
      triggered confusion and/or incorrect conceptual ideas. We argue that 1)
      illustrators need to be more clear and consistent when using arrow symbols, 2)
      instructors need to be cognizant of the level of clarity of representations used
      during instruction, and 3) instructors should help students learn how to
      interpret representations containing arrows.

PMID- 29351910
TI  - Visual Literacy in Bloom: Using Bloom's Taxonomy to Support Visual Learning
      Skills.
AB  - Vision and Change identifies science communication as one of the core
      competencies in undergraduate biology. Visual representations are an integral
      part of science communication, allowing ideas to be shared among and between
      scientists and the public. As such, development of scientific visual literacy
      should be a desired outcome of undergraduate instruction. We developed the
      Visualization Blooming Tool (VBT), an adaptation of Bloom's taxonomy specifically
      focused on visual representations, to aid instructors in designing instruction
      and assessments to target scientific visual literacy in undergraduate
      instruction. In this article, we identify the need for the VBT, describe its
      development, and provide concrete examples of its application to a curriculum
      redesign effort in undergraduate biochemistry.

PMID- 29351911
TI  - Does Context Matter? Convergent and Divergent Findings in the Cross-Institutional
      Evaluation of Graduate Teaching Assistant Professional Development Programs.
AB  - Graduate teaching assistants (GTAs) play important instructional roles in
      introductory science courses, yet they often have little training in pedagogy.
      The most common form of teaching professional development (PD) for GTAs is a
      presemester workshop held at the course, department, or college level. In this
      study, we compare the effectiveness of presemester workshops at three
      northeastern research universities, each of which incorporated scientific
      teaching as the pedagogical content framework. The comparison of GTA PD program
      outcomes at three different institutions is intended to test theoretical
      assertions about the key role of contextual factors in GTA PD efficacy. Pretest
      and posttest surveys were used to assess changes in GTA teaching self-efficacy
      and anxiety following the workshops, and an objective test was used to assess
      pedagogical knowledge. Analysis of pretest/posttest data revealed statistically
      significant gains in GTA teaching self-efficacy and pedagogical knowledge and
      reductions in teaching anxiety across sites. Changes in teaching anxiety and self
      efficacy, but not pedagogical knowledge, differed by training program. Student
      ratings of GTAs at two sites showed that students had positive perceptions of
      GTAs in all teaching dimensions, and relatively small differences in student
      ratings of GTAs were observed between institutions. Divergent findings for some
      outcome variables suggest that program efficacy was influenced as hypothesized by
      contextual factors such as GTA teaching experience.

PMID- 29351912
TI  - A Longitudinal Study of How Quality Mentorship and Research Experience Integrate
      Underrepresented Minorities into STEM Careers.
AB  - African Americans, Latinos, and Native Americans are historically
      underrepresented minorities (URMs) among science, technology, engineering, and
      mathematics (STEM) degree earners. Viewed from a perspective of social influence,
      this pattern suggests that URMs do not integrate into the STEM academic community
      at the same rate as non-URM students. Estrada and colleagues recently showed that
      Kelman's tripartite integration model of social influence (TIMSI) predicted URM
      persistence into science fields. In this paper, we longitudinally examine the
      integration of URMs into the STEM community by using growth-curve analyses to
      measure the development of TIMIS's key variables (science efficacy, identity, and
      values) from junior year through the postbaccalaureate year. Results showed that
      quality mentorship and research experience occurring in the junior and senior
      years were positively related to student science efficacy, identity, and values
      at that same time period. Longitudinal modeling of TIMSI further shows that,
      while efficacy is important, and perhaps a necessary predictor of moving toward a
      STEM career, past experiences of efficacy may not be sufficient for maintaining
      longer-term persistence. In contrast, science identity and values do continue to
      be predictive of STEM career pathway persistence up to 4 years after graduation.

PMID- 29351914
TI  - High-resolution transcription maps reveal the widespread impact of roadblock
      termination in yeast.
AB  - Transcription termination delimits transcription units but also plays important
      roles in limiting pervasive transcription. We have previously shown that
      transcription termination occurs when elongating RNA polymerase II (RNAPII)
      collides with the DNA-bound general transcription factor Reb1. We demonstrate
      here that many different DNA-binding proteins can induce termination by a similar
      roadblock (RB) mechanism. We generated high-resolution transcription maps by the
      direct detection of RNAPII upon nuclear depletion of two essential RB factors or
      when the canonical termination pathways for coding and non-coding RNAs are
      defective. We show that RB termination occurs genomewide and functions
      independently of (and redundantly with) the main transcription termination
      pathways. We provide evidence that transcriptional readthrough at canonical
      terminators is a significant source of pervasive transcription, which is
      controlled to a large extent by RB termination. Finally, we demonstrate the
      occurrence of RB termination around centromeres and tRNA genes, which we suggest
      shields these regions from RNAPII to preserve their functional integrity.

PMID- 29351915
TI  - Chronic hip pain.

PMID- 29351916
TI  - Pathways Impacted by Genomic Alterations in Pulmonary Carcinoid Tumors.
AB  - Purpose: Pulmonary carcinoid tumors account for up to 5% of all lung malignancies
      in adults, comprise 30% of all carcinoid malignancies, and are defined
      histologically as typical carcinoid (TC) and atypical carcinoid (AC) tumors. The
      role of specific genomic alterations in the pathogenesis of pulmonary carcinoid
      tumors remains poorly understood. We sought to identify genomic alterations and
      pathways that are deregulated in these tumors to find novel therapeutic targets
      for pulmonary carcinoid tumors.Experimental Design: We performed integrated
      genomic analysis of carcinoid tumors comprising whole genome and exome
      sequencing, mRNA expression profiling and SNP genotyping of specimens from normal
      lung, TC and AC, and small cell lung carcinoma (SCLC) to fully represent the lung
      neuroendocrine tumor spectrum.Results: Analysis of sequencing data found
      recurrent mutations in cancer genes including ATP1A2, CNNM1, MACF1, RAB38, NF1,
      RAD51C, TAF1L, EPHB2, POLR3B, and AGFG1 The mutated genes are involved in
      biological processes including cellular metabolism, cell division cycle, cell
      death, apoptosis, and immune regulation. The top most significantly mutated genes
      were TMEM41B, DEFB127, WDYHV1, and TBPL1 Pathway analysis of significantly
      mutated and cancer driver genes implicated MAPK/ERK and amyloid beta precursor
      protein (APP) pathways whereas analysis of CNV and gene expression data suggested
      deregulation of the NF-kappaB and MAPK/ERK pathways. The mutation signature was
      predominantly C>T and T>C transitions with a minor contribution of T>G
      transversions.Conclusions: This study identified mutated genes affecting cancer
      relevant pathways and biological processes that could provide opportunities for
      developing targeted therapies for pulmonary carcinoid tumors. Clin Cancer Res;
      24(7); 1691-704. (c)2018 AACR.

PMID- 29351913
TI  - The RIG-I-like receptor LGP2 inhibits Dicer-dependent processing of long double
      stranded RNA and blocks RNA interference in mammalian cells.
AB  - In vertebrates, the presence of viral RNA in the cytosol is sensed by members of
      the RIG-I-like receptor (RLR) family, which signal to induce production of type I
      interferons (IFN). These key antiviral cytokines act in a paracrine and autocrine
      manner to induce hundreds of interferon-stimulated genes (ISGs), whose protein
      products restrict viral entry, replication and budding. ISGs include the RLRs
      themselves: RIG-I, MDA5 and, the least-studied family member, LGP2. In contrast,
      the IFN system is absent in plants and invertebrates, which defend themselves
      from viral intruders using RNA interference (RNAi). In RNAi, the endoribonuclease
      Dicer cleaves virus-derived double-stranded RNA (dsRNA) into small interfering
      RNAs (siRNAs) that target complementary viral RNA for cleavage. Interestingly,
      the RNAi machinery is conserved in mammals, and we have recently demonstrated
      that it is able to participate in mammalian antiviral defence in conditions in
      which the IFN system is suppressed. In contrast, when the IFN system is active,
      one or more ISGs act to mask or suppress antiviral RNAi. Here, we demonstrate
      that LGP2 constitutes one of the ISGs that can inhibit antiviral RNAi in mammals.
      We show that LGP2 associates with Dicer and inhibits cleavage of dsRNA into
      siRNAs both in vitro and in cells. Further, we show that in differentiated cells
      lacking components of the IFN response, ectopic expression of LGP2 interferes
      with RNAi-dependent suppression of gene expression. Conversely, genetic loss of
      LGP2 uncovers dsRNA-mediated RNAi albeit less strongly than complete loss of the
      IFN system. Thus, the inefficiency of RNAi as a mechanism of antiviral defence in
      mammalian somatic cells can be in part attributed to Dicer inhibition by LGP2
      induced by type I IFNs. LGP2-mediated antagonism of dsRNA-mediated RNAi may help
      ensure that viral dsRNA substrates are preserved in order to serve as targets of
      antiviral ISG proteins.

PMID- 29351917
TI  - A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma.
AB  - Purpose: The classification of medulloblastoma into WNT, SHH, group 3, and group
      4 subgroups has become of critical importance for patient risk stratification and
      subgroup-tailored clinical trials. Here, we aimed to develop a simplified,
      clinically applicable classification approach that can be implemented in the
      majority of centers treating patients with medulloblastoma.Experimental Design:
      We analyzed 1,577 samples comprising previously published DNA methylation
      microarray data (913 medulloblastomas, 457 non-medulloblastoma tumors, 85 normal
      tissues), and 122 frozen and formalin-fixed paraffin-embedded medulloblastoma
      samples. Biomarkers were identified applying stringent selection filters and
      Linear Discriminant Analysis (LDA) method, and validated using DNA methylation
      microarray data, bisulfite pyrosequencing, and direct-bisulfite
      sequencing.Results: Using a LDA-based approach, we developed and validated a
      prediction method (EpiWNT-SHH classifier) based on six epigenetic biomarkers that
      allowed for rapid classification of medulloblastoma into the clinically relevant
      subgroups WNT, SHH, and non-WNT/non-SHH with excellent concordance (>99%) with
      current gold-standard methods, DNA methylation microarray, and gene signature
      profiling analysis. The EpiWNT-SHH classifier showed high prediction capacity
      using both frozen and formalin-fixed material, as well as diverse DNA methylation
      detection methods. Similarly, we developed a classifier specific for group 3 and
      group 4 tumors, based on five biomarkers (EpiG3-G4) with good discriminatory
      capacity, allowing for correct assignment of more than 92% of tumors. EpiWNT-SHH
      and EpiG3-G4 methylation profiles remained stable across tumor primary,
      metastasis, and relapse samples.Conclusions: The EpiWNT-SHH and EpiG3-G4
      classifiers represent a new simplified approach for accurate, rapid, and cost
      effective molecular classification of single medulloblastoma DNA samples, using
      clinically applicable DNA methylation detection methods. Clin Cancer Res; 24(6);
      1355-63. (c)2018 AACR.

PMID- 29351918
TI  - Personalized Chemosensitivity Assays for Mesothelioma: Are They Worth the Effort?
AB  - Cell lines formed from an individual's tumor can be used to predict response to
      specific therapies and determine genomic predictors. For mesothelioma, where
      chemotherapy remains the backbone of current therapeutic paradigms, such assays
      could be used to treat patients with the most effective agents specific to their
      "chemical profile." Clin Cancer Res; 24(7); 1513-5. (c)2018 AACRSee related
      article by Schunselaar et al., p. 1761.

PMID- 29351919
TI  - High Yield of Pathogenic Germline Mutations Causative or Likely Causative of the
      Cancer Phenotype in Selected Children with Cancer.
AB  - Purpose: In many children with cancer and characteristics suggestive of a genetic
      predisposition syndrome, the genetic cause is still unknown. We studied the yield
      of pathogenic mutations by applying whole-exome sequencing on a selected cohort
      of children with cancer.Experimental Design: To identify mutations in known and
      novel cancer-predisposing genes, we performed trio-based whole-exome sequencing
      on germline DNA of 40 selected children and their parents. These children were
      diagnosed with cancer and had at least one of the following features: (1)
      intellectual disability and/or congenital anomalies, (2) multiple malignancies,
      (3) family history of cancer, or (4) an adult type of cancer. We first analyzed
      the sequence data for germline mutations in 146 known cancer-predisposing genes.
      If no causative mutation was found, the analysis was extended to the whole
      exome.Results: Four patients carried causative mutations in a known cancer
      predisposing gene: TP53 and DICER1 (n = 3). In another 4 patients, exome
      sequencing revealed mutations causing syndromes that might have contributed to
      the malignancy (EP300-based Rubinstein-Taybi syndrome, ARID1A-based Coffin-Siris
      syndrome, ACTB-based Baraitser-Winter syndrome, and EZH2-based Weaver syndrome).
      In addition, we identified two genes, KDM3B and TYK2, which are possibly involved
      in genetic cancer predisposition.Conclusions: In our selected cohort of patients,
      pathogenic germline mutations causative or likely causative of the cancer
      phenotype were found in 8 patients, and two possible novel cancer-predisposing
      genes were identified. Therewith, our study shows the added value of sequencing
      beyond a cancer gene panel in selected patients, to recognize childhood cancer
      predisposition. Clin Cancer Res; 24(7); 1594-603. (c)2018 AACR.

PMID- 29351920
TI  - Exceptional Response to Pembrolizumab in a Metastatic, Chemotherapy/Radiation
      Resistant Ovarian Cancer Patient Harboring a PD-L1-Genetic Rearrangement.
AB  - Purpose: Ovarian carcinoma no longer responsive to surgery and chemotherapy
      remains an incurable disease. Alternative therapeutic options remain desperately
      needed.Patients and Methods: We describe a heavily pretreated patient with
      ovarian cancer with recurrent disease experiencing a remarkable clinical response
      to treatment with the anti-PD1 immune checkpoint inhibitor pembrolizumab. The
      clinical, pathological, and genomic characteristics of this exceptional ovarian
      cancer responder were carefully investigated using immunohistochemistry (IHC),
      quantitative multiplex fluorescence methods (i.e., automated quantitative
      analysis, AQUA) and whole-exome sequencing (WES) techniques.Results: The patient
      harbored a recurrent/metastatic radiation and chemotherapy-resistant high-grade
      ovarian carcinoma with clear cell features. While progressing on any standard
      treatment modality, she demonstrated a remarkable complete response to the anti
      PD1 immune checkpoint inhibitor pembrolizumab. WES results were notable for the
      presence a relative low number of mutations (tumor mutation load/Mb = 4.31, total
      mutations = 164) and a peculiar structural variant disrupting the 3' region of
      the PD-L1 gene causing aberrant PD-L1 surface expression as confirmed by IHC and
      AQUA technology. Heavy infiltration of the PD-L1-mutated and PD-L1-overexpressing
      tumor with T-cell lymphocytes (i.e., CD4+/CD8+ TIL), CD68+ macrophages, and CD20+
      B cells was detected in the surgical specimen strongly suggesting immune evasion
      as a key mechanism of tumor growth and survival. Patient's complete clinical
      responses remain unchanged at the time of the writing of this report with no
      significant side effects reported to date.Conclusions: Anti-PD1 inhibitors may
      represent a novel treatment option for recurrent/metastatic human tumors
      refractory to salvage treatment harboring PD-L1 gene structural variations
      causing aberrant PD-L1 expression. Clin Cancer Res; 24(14); 3282-91. (c)2018
      AACRSee related commentary by Lheureux, p. 3233.

PMID- 29351921
TI  - Inhibitory Effects of Endogenous Linoleic Acid and Glutaric Acid on the Renal
      Glucuronidation of Berberrubine in Mice and on Recombinant Human UGT1A7, 1A8, and
      1A9.
AB  - Berberrubine (BRB) has a strong lipid-lowering effect and can be extensively
      metabolized into berberrubine-9-O-beta-d-glucuronide (BRBG) in vivo. Recently,
      pharmacokinetics studies showed that the production of BRBG was significantly
      decreased in the urine of mice fed with a high-fat diet (HFD), indicating a
      decreased glucuronidation capacity. Based on the UDP-glucuronosyltransferase
      (UGT) isoform identification, hepatic and renal microsomal incubation,
      glucuronidation was examined to suggest the metabolism of BRB in liver and
      kidneys. The results showed that the renal UGT activity for metabolizing BRB
      markedly decreased, which may be highly related to the decreased expression and
      activity of renal Ugt1a7c. Surprisingly, in vitro studies revealed neither BRB
      nor BRBG inhibited the renal UGT activity. By employing an integrated strategy of
      metabolomics and pharmacokinetics, we identified and confirmed for the first time
      the inhibitory effect of some potential endogenous molecules on the renal
      glucuronidation of C57BL/6J mice, such as glutaric acid (GA) and linoleic acid
      (LA). By employing recombinant human UGTs, we found that GA and LA efficiently
      affect the activity of recombinant human UGT1A7, 1A9, and 1A8 at their normal or
      abnormal physiologic levels in vivo. GA (2 mM) markedly inhibited the activity of
      UGT1A7 by 89.4% and UGT1A9 by 32.8%. The inhibition rates reached 99.3% for
      UGT1A9, 48.3% for UGT1A7, and 46.8% for UGT1A8 with LA at 200 MUM. It has been
      suggested that the endogenous molecules have the potential to affect the
      efficiency of glucuronidation, which might be a key factor contributing to
      individual differences in drug metabolism.

PMID- 29351923
TI  - Association of Surgeons in Training responds to GMC erasure case.

PMID- 29351922
TI  - Activation of Constitutive Androstane Receptor Ameliorates Renal Ischemia
      Reperfusion-Induced Kidney and Liver Injury.
AB  - Acute kidney injury (AKI) is associate with high mortality. Despite evidence of
      AKI-induced distant organ injury, a relationship between AKI and liver injury has
      not been clearly established. The goal of this study is to investigate whether
      renal ischemia-reperfusion (IR) can affect liver pathophysiology. We showed that
      renal IR in mice induced fatty liver and compromised liver function through the
      downregulation of constitutive androstane receptor (CAR; -90.4%) and inhibition
      of hepatic very-low-density lipoprotein triglyceride (VLDL-TG) secretion (
      28.4%). Treatment of mice with the CAR agonist 1,4-bis[2-(3,5
      dichloropyridyloxy)] benzene (TCPOBOP) prevented the development of AKI-induced
      fatty liver and liver injury, which was associated with the attenuation of AKI
      induced inhibition of VLDL-TG secretion. The hepatoprotective effect of TCPOBOP
      was abolished in CAR-/- mice. Interestingly, alleviation of fatty liver by
      TCPOBOP also improved the kidney function, whereas CAR ablation sensitized mice
      to AKI-induced kidney injury and lethality. The serum concentrations of
      interleukin-6 (IL-6) were elevated by 27-fold after renal IR, but were normalized
      in TCPOBOP-treated AKI mice, suggesting that the increased release of IL-6 from
      the kidney may have mediated the AKI responsive liver injury. Taken together, our
      results revealed an interesting kidney-liver organ cross-talk in response to AKI.
      Given the importance of CAR in the pathogenesis of renal IR-induced fatty liver
      and impaired kidney function, fatty liver can be considered as an important risk
      factor for kidney injury, and a timely management of hepatic steatosis by CAR
      activation may help to restore kidney function in patients with AKI or kidney
      transplant.

PMID- 29351926
TI  - BET 1: Is routine irrigation of a cutaneous abscess necessary?
AB  - A short cut review was carried out to establish whether the addition of
      irrigation of the abscess cavity improved outcomes after incision and drainage of
      a cutaneous abscess. One paper presented the best evidence to answer the clinical
      question. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of this paper are
      tabulated. It is concluded that in adult patients with cutaneous abscesses
      routine irrigation during incision and drainage does not improve clinical
      outcomes.

PMID- 29351924
TI  - A man with sudden loss of consciousness.

PMID- 29351927
TI  - BET 2: Is early chemical thromboprophylaxis safe in patients with blunt trauma
      solid organ injury (SOI) undergoing non-operative management (NOM)?
AB  - A short cut review was carried out to establish whether chemical
      thromboprophylaxis was a safe early intervention in patients with solid organ
      injury that is being managed non-operatively. Eight papers presented the best
      evidence to answer the clinical question. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of these papers are tabulated. It is concluded that there is
      inadequate evidence assessing safety of low molecular weight heparin (LMWH)
      within 24 hours of trauma. The current available evidence does suggest that
      administration of LMWH within 48 hours is safe in non-operative management of
      patients who have sustained solid organ injury from blunt trauma.

PMID- 29351928
TI  - Mapping and Quantification of Over 2000 O-linked Glycopeptides in Activated Human
      T Cells with Isotope-Targeted Glycoproteomics (Isotag).
AB  - Post-translational modifications (PTMs) on proteins often function to regulate
      signaling cascades, with the activation of T cells during an adaptive immune
      response being a classic example. Mounting evidence indicates that the
      modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), the only
      mammalian glycan found on nuclear and cytoplasmic proteins, helps regulate T cell
      activation. Yet, a mechanistic understanding of how O-GlcNAc functions in T cell
      activation remains elusive, partly because of the difficulties in mapping and
      quantifying O-GlcNAc sites. Thus, to advance insight into the role of O-GlcNAc in
      T cell activation, we performed glycosite mapping studies via direct glycopeptide
      measurement on resting and activated primary human T cells with a technique
      termed Isotope Targeted Glycoproteomics. This approach led to the identification
      of 2219 intact O-linked glycopeptides across 1045 glycoproteins. A significant
      proportion (>45%) of the identified O-GlcNAc sites lie near or coincide with a
      known phosphorylation site, supporting the potential for PTM crosstalk.
      Consistent with other studies, we find that O-GlcNAc sites in T cells lack a
      strict consensus sequence. To validate our results, we employed gel shift assays
      based on conjugating mass tags to O-GlcNAc groups. Notably, we observed that the
      transcription factors c-JUN and JUNB show higher levels of O-GlcNAc glycosylation
      and higher levels of expression in activated T cells. Overall, our findings
      provide a quantitative characterization of O-GlcNAc glycoproteins and their
      corresponding modification sites in primary human T cells, which will facilitate
      mechanistic studies into the function of O-GlcNAc in T cell activation.

PMID- 29351929
TI  - Prevalence of invehicle smoking and secondhand smoke exposure in Uruguay.
AB  - INTRODUCTION: Protection from secondhand smoke (SHS) is one of the fundamental
      principles of the WHO Framework Convention for Tobacco Control. Objective data on
      SHS exposure in vehicles in South America is scarce. This study aimed to estimate
      prevalence of smoking inside vehicles. METHODS: The point prevalence of smoking
      in vehicles was observed, and a method for estimating smoking prevalence was
      piloted. RESULTS: We observed 10 011 vehicles. In 219 (2.2%; 95% CI 1.91 to 2.49)
      of them, smoking was observed, and in 29.2% of these, another person was exposed
      to SHS. According to the 'expansion factor' we constructed, direct observation
      detected one of six to one to nine vehicles in which smoking occurred. The
      observed prevalence of smoking in vehicles (2.2%) could reflect a real prevalence
      between 12% and 19%. In 29.2% (95% CI 23.6 to 35.5) and 4.6% (95% CI 2.2 to 8.3)
      of vehicles in which smoking was observed, another adult or a child,
      respectively, was exposed to SHS. CONCLUSIONS: Smoking was estimated to occur in
      12%-19% of vehicles, with involuntary exposure in one of three of vehicles
      observed. These data underscore a need for new public policies to eliminate SHS
      in vehicles to protect public health.

PMID- 29351930
TI  - Effect of the Smoke-Free Illinois Act on casino admissions and revenue.
AB  - OBJECTIVE: As part of the Smoke-Free Illinois Act, smoking on the gambling floors
      of all commercial casinos in Illinois became prohibited. This study examined the
      effects of the Smoke-Free Illinois Act on casino admissions per-capita and real
      per-capita adjusted gross receipts using 18 years of data (10 years before and 8
      years after the Illinois law went into effect). METHODS: We employed a difference
      in-difference regression technique using monthly data for the states of Illinois,
      Indiana, Iowa and Missouri and control for numerous determinants expected to
      affect casino admissions and revenue. RESULTS: The Smoke-free Illinois Act was
      found not to be a statistically significant determinant of per-capita casino
      admissions and of real per-capita gross adjusted receipts in all the models we
      estimated. CONCLUSIONS: The estimates from this study clearly indicated that the
      Illinois law that banned smoking in casinos has had no significant negative
      economic consequences for casinos in terms of per-capita admissions or revenues.

PMID- 29351931
TI  - Stent-assisted coil embolization on down-the-barrel view with spring-shaped
      microcatheter in patient with M1 ultrawide necked circumferential aneurysm.
AB  - Herein, we describe a technique for stent-assisted coil embolization with a
      spring-shaped microcatheter in a patient with an M1 ultrawide-necked
      circumferential aneurysm in the middle cerebral artery (MCA). A 49-year-old man
      was referred for treatment of an incidentally detected M1 large-circumference
      aneurysm on magnetic resonance angiography. Subsequent digital subtraction
      angiography revealed an 18.2*16.5 mm ultrawide-necked circumferential aneurysm on
      the distal M1 portion of the left MCA, and we planned stent-assisted coil
      embolization using a spring-shaped microcatheter. After we deployed the stent, we
      performed coil embolization under the down-the-barrel view by pulling out the
      microcatheter little by little. Using this technique, we could fill the coil mass
      evenly into the aneurysmal sac around the stent. And there were no immediate or
      delayed complications after the procedure. Stent-assisted coiling using a spring
      shaped microcatheter is a useful and safe technique for treating ultrawide-necked
      circumferential aneurysm or fusiform aneurysms.

PMID- 29351932
TI  - Megaduodenum in a 59-year-old man: a very late postoperative complication after
      duodenal atresia.
AB  - Intestinal malformations are common defects of the newborn, treated in
      experienced centres. Reports on long-term follow-up and associated complications
      are scarce, possibly leading to misinterpretation of clinical signs and symptoms
      in adulthood. To prevent treatment errors, it is important that physicians are
      aware of long-term complications of intestinal malformations.

PMID- 29351933
TI  - Vanadium allergy following total knee arthroplasty.
AB  - Allergic reactions to metals following joint arthroplasty represent a rare and
      poorly understood phenomenon. Much is still unknown regarding the natural history
      of this complication, and how it can best be prevented and managed. We present a
      case of a 68-year-old woman who underwent a left total knee arthroplasty for
      treatment of osteoarthritis. After an initial uneventful postoperative course,
      she developed a troublesome erythematous rash both around the incision site and
      over her trunk. Blood testing revealed no evidence of infection and clinically
      her prosthesis was functioning well. Skin patch testing revealed positive results
      for vanadium (+) and palladium (+). Her cutaneous symptoms are currently being
      managed conservatively and have shown a partial response to topical steroids.
      Revision surgery remains a long-term treatment option should conservative therapy
      fail; however, it would require a custom-made prosthesis as no standard tibial
      component is free from vanadium.

PMID- 29351934
TI  - Continuous subcutaneous levetiracetam in end-of-life care.
AB  - Seizures constitute a determining aspect in quality of life and are frequently
      challenging in palliative care-a field where treatment has yet to be
      standardised. Levetiracetam-a new generation anticonvulsant-has proved efficacy
      both through oral, as well as intravenous administration in the general
      population. This case reports on the use of continuous subcutaneous levetiracetam
      to effectively control seizures in a terminally ill patient without patent oral
      route.

PMID- 29351936
TI  - Intravitreal bevacizumab for postviral fever retinitis: a novel approach for
      early resolution of macular oedema.
AB  - Severe macular oedema causing marked loss of vision is seen in cases of retinitis
      developing postviral fever. The use of antivascular endothelial growth factor
      agents for macular oedema and submacular fluid secondary to viral retinitis has
      not been studied or well established in the past. We report a case series of two
      patients of postviral retinitis with severe macular oedema resistant to steroid
      therapy, treated with intravitreal bevacizumab. The patients showed significant
      symptomatic improvement in the visual acuity. The retinitis lesions resolved
      slowly and macular oedema regressed. Bevacizumab appears to be a safe and useful
      agent to manage macular oedema subsequent to postviral retinitis. An early
      resolution of macular oedema helps in the preservation of visual acuity which
      left untreated can cause severe visual loss.

PMID- 29351935
TI  - An adult case with shigellosis-associated encephalopathy.
AB  - A 45-year-old man was presented at the emergency department with altered
      neurological status and a 1-day history of diarrhoea and fever. The patient's
      sexual history revealed multiple male partners. As bacterial meningitis or viral
      encephalitis was suspected, treatment was started accordingly. Cerebrospinal
      fluid investigations only showed a slight increase of leucocytes, and
      microbiological studies remained negative. Stool culture revealed Shigella
      flexneri, after which Shigella-associated encephalopathy was suspected. The
      patient recovered quickly with antibiotic treatment. The incidence of Shigella
      infections in the Western world is rising due to sexual transmission among men
      who have sex with men. Shigella-induced encephalopathy is a notorious
      complication among children with a severe form known as the Ekiri syndrome,
      though rarely seen in adults. This is the second report of encephalopathy in an
      adult with S. flexneri enteric infection.

PMID- 29351937
TI  - Anterior choroidal artery infarction.

PMID- 29351938
TI  - Unusual skin mass (primary cutaneous mucinous carcinoma).
AB  - Primary mucinous carcinoma of the skin is a rare malignant tumour of sweat gland
      origin. Diagnostic concerns include its deceptively benign appearance in some
      cases and the difficulty in differentiating it from secondary mucinous carcinoma
      of skin metastasising from a primary source elsewhere. A case of a 75-year-old
      man is reported who presented with a slowly growing painless mass near the
      lateral canthus of the right eye for about 2 years. Clinically, a diagnosis of
      basal cell carcinoma was made whereas histopathology revealed mucinous carcinoma
      of the skin. The primary source of the tumour could not be found on detailed
      physical examination and laboratory investigations. Immunohistochemistry,
      performed later, was consistent with primary cutaneous mucinous carcinoma.

PMID- 29351939
TI  - Retroperitoneal bile leak after laparoscopic cholecystectomy.
AB  - Bile duct injury (BDI) is a well-recognised complication of laparoscopic
      cholecystectomy (LC). Following a BDI, bile usually leaks into the peritoneal
      space and causes biliary peritonitis. This manifests as non-specific abdominal
      pain and fever occurring several days after the surgery. It can be managed by
      laparoscopic washout with or without bile duct repair. We present a rare case of
      retroperitoneal bile leak post-LC. The mechanism of injury here was likely
      partial avulsion from excessive traction of the cystic duct during intraoperative
      cholangiogram. Diagnosing retroperitoneal bile leak can be difficult because it
      is extremely rare and the presenting symptoms can be similar to an
      intraperitoneal bile leak. A high index of clinical suspicion is required. In
      cases of suspected bile leak, any mismatch between the exploratory laparoscopic
      findings and imaging findings should alert surgeons to consider the rare
      possibility of a retroperitoneal bile leak.

PMID- 29351940
TI  - Angiodysplastic Sturge Weber syndrome.

PMID- 29351941
TI  - Moyamoya tipping point: fatal bilateral MCA territory infarction following
      cocaine abuse.

PMID- 29351942
TI  - Abnormal deep dorsal vein resulting in veno-occlusive erectile dysfunction.
AB  - A 59-year-old man with a 6-year history of erectile dysfunction presented to the
      andrology outpatient clinic. Multimodality assessment with ultrasound, MRI
      venography and fluoroscopic venography demonstrated an aberrant emissary vein
      arising from the corporal bodies causing venogenic erectile dysfunction.
      Selective coil embolisation of the collateral vein resulted in an almost
      immediate and sustained improvement in his erections.

PMID- 29351943
TI  - Role of modified Eloesser flap in the treatment of bronchopleural fistula caused
      by pulmonary coccidioidomycosis.

PMID- 29351944
TI  - Sacral bone cyst treatment resulting in paraplegia.

PMID- 29351946
TI  - Popliteal artery entrapment syndrome: an approach to diagnosis and management.

PMID- 29351945
TI  - Concurrent endocrine neoplasias in dogs and cats: a retrospective study (2004
      2014).
AB  - Multiple endocrine neoplasia (MEN) is a well-known syndrome in human medicine,
      whereas only a few cases of concurrent endocrine neoplasias have been reported in
      dogs and cats. The aim of this study was to evaluate the prevalence of concurrent
      endocrine neoplasias in dogs and cats at our clinic, identify possible breed and
      sex predispositions and investigate similarities with MEN syndromes in humans.
      Postmortem reports of 951 dogs and 1155 cats that died or were euthanased at the
      Clinic for Small Animal Internal Medicine, University of Zurich, between 2004 and
      2014 were reviewed, and animals with at least two concurrent endocrine neoplasias
      and/or hyperplasias were included. Twenty dogs and 15 cats met the inclusion
      criteria. In dogs, the adrenal glands were most commonly affected. Multiple
      tumours affecting the adrenal glands and the association of these tumours with
      pituitary adenomas were the most common tumour combinations. Only one dog had a
      combination resembling human MEN type 1 syndrome (pituitary adenoma and
      insulinoma). In cats, the thyroid glands were most commonly affected and there
      were no similarities to human MEN syndromes. The prevalence of concurrent
      endocrine neoplasia was 2.1 per cent in dogs and 1.3 per cent in cats and MEN
      like syndromes are very rare in these species.

PMID- 29351947
TI  - Advancing adherence research in sport injury prevention.

PMID- 29351948
TI  - Order from chaos: unravelling the determinants of mixed martial arts performance
      (PhD Academy Award).

PMID- 29351949
TI  - PT and OT Helper Golf Elbow: a mobile app user guide for getting a grip on medial
      epicondylalgia.

PMID- 29351950
TI  - Use of event-specific tertiles to analyse the relationship between serum
      androgens and athletic performance in women.

PMID- 29351951
TI  - Hyperandrogenism controversy in elite women's sport: an examination and critique
      of recent evidence.

PMID- 29351952
TI  - Bright Spots, physical activity investments that work: Choose to Move: scaling up
      a physical activity model for older adults.

PMID- 29351953
TI  - Developing consensus on clinical assessment of acute lateral ankle sprain
      injuries: protocol for an international and multidisciplinary modified Delphi
      process.

PMID- 29351954
TI  - Bright spots, physical activity investments that work: Indigenous Marathon
      Foundation.

PMID- 29351956
TI  - What counts as 'the evidence'? A need for an urgent review of injury risk in
      school rugby.

PMID- 29351955
TI  - Mitigating risk of injury in alpine skiing in the Pyeongchang 2018 Paralympic
      Winter Games: the time is now!

PMID- 29351957
TI  - Understanding and removing barriers to physical activity: one key in addressing
      child obesity.

PMID- 29351958
TI  - Recent data from radiofrequency denervation trials further emphasise that
      treating nociception is not the same as treating pain.

PMID- 29351959
TI  - Diagnosis and Significance of Pulmonary Microvascular Disease in Diabetes.
AB  - OBJECTIVE: To determine whether pulmonary microvascular disease is detectable in
      subjects with diabetes and associated with diminished exercise capacity using a
      novel echocardiographic marker quantifying the pulmonary transit of agitated
      contrast bubbles (PTAC). RESEARCH DESIGN AND METHODS: Sixty participants (40 with
      diabetes and 20 control subjects) performed cardiopulmonary (maximal oxygen
      consumption [VO2peak]) and semisupine bicycle echocardiography exercise tests
      within a 1-week period. Pulmonary microvascular disease was assessed using PTAC
      (the number of bubbles traversing the pulmonary circulation to reach the left
      ventricle, categorized as low PTAC or high PTAC). Echocardiographic measures of
      cardiac output, pulmonary artery pressures, and biventricular function were
      obtained during exercise. RESULTS: Subjects with diabetes and control subjects
      were of similar age (44 +/- 13 vs. 43 +/- 13 years, P = 0.87) and sex composition
      (70% vs. 65% male, P = 0.7). At peak exercise, low PTAC was present in more
      participants with diabetes than control subjects (41% vs. 12.5%, chi2P = 0.041)
      and, in particular, in more subjects with diabetes with microvascular
      complications compared with both those without complications and control subjects
      (55% vs. 26% vs. 13%, chi2P = 0.02). When compared with high PTAC, low PTAC was
      associated with a 24% lower VO2peak (P = 0.006), reduced right ventricular
      function (P = 0.015), and greater pulmonary artery pressures during exercise (P =
      0.02). CONCLUSIONS: PTAC is reduced in diabetes, particularly in the presence of
      microvascular pathology in other vascular beds, suggesting that it may be a
      meaningful indicator of pulmonary microvascular disease with important
      consequences for cardiovascular function and exercise capacity.

PMID- 29351960
TI  - The Impact of Diabetes on Breast Cancer Treatments and Outcomes: A Population
      Based Study.
AB  - OBJECTIVE: Women with breast cancer and diabetes face worse outcomes than those
      with breast cancer without diabetes; however, the contribution of comorbidity to
      these disparities remains unclear. We evaluated the impact of diabetes on receipt
      of cancer treatments as well as mortality while accounting for other
      comorbidities. RESEARCH DESIGN AND METHODS: Ontario administrative databases were
      used to compare the rate of receipt of breast cancer treatments between women
      with and without diabetes. We also performed adjusted cause-specific hazard
      models to account for comorbidities when evaluating differences in treatments
      received and mortality outcomes between the two groups. RESULTS: Women with
      diabetes and stage III breast cancer were slightly less likely to receive
      chemotherapy (relative risk [RR] 0.93 [95% CI 0.89-0.97]), although this
      difference was not significant when we adjusted for comorbidities (adjusted
      hazard ratio [aHR] 1.03 [95% CI 0.93-1.13]). We saw similar trends for receipt of
      guideline-adherent radiotherapy (RR 0.97 [0.95-0.99], aHR 0.98 [0.94-1.02]). All
      cause mortality was increased in women with diabetes after adjusting for
      comorbidities (aHR 1.16 [1.06-1.27]), but breast cancer-specific mortality was
      not increased overall. Women with a longer duration of diabetes and those with
      preexisting cardiovascular disease had increased all-cause and cancer-specific
      mortality. CONCLUSIONS: Although cancer treatments received were similar between
      women with and without diabetes, breast cancer-specific mortality remains higher
      among women with diabetes who have longer diabetes duration or preexisting
      cardiovascular disease. This study uncovers new information about key risk
      factors for poorer prognosis in women with diabetes and breast cancer.

PMID- 29351961
TI  - Occupational Therapy Intervention Improves Glycemic Control and Quality of Life
      Among Young Adults With Diabetes: the Resilient, Empowered, Active Living with
      Diabetes (REAL Diabetes) Randomized Controlled Trial.
AB  - OBJECTIVE: To assess the efficacy of a manualized occupational therapy (OT)
      intervention (Resilient, Empowered, Active Living with Diabetes [REAL Diabetes])
      to improve glycemic control and psychosocial well-being among ethnically diverse
      young adults with low socioeconomic status (SES) who have type 1 or type 2
      diabetes. RESEARCH DESIGN AND METHODS: Eighty-one young adults (age 22.6 +/- 3.5
      years; hemoglobin A1c [HbA1c] = 10.8%/95 mmol/mol +/- 1.9%/20.8 mmol/mol) were
      randomly assigned to the REAL Diabetes intervention group (IG) or an attention
      control group (CG) over 6 months. IG participants received biweekly sessions
      guided by a manual composed of seven content modules; CG participants received
      standardized educational materials and biweekly phone calls. Blinded assessors
      collected data at baseline and 6 months. The primary outcome was HbA1c; secondary
      outcomes included diabetes self-care, diabetes-related quality of life (QOL),
      diabetes distress, depressive symptoms, and life satisfaction. Change scores were
      analyzed using Wilcoxon rank sum tests. RESULTS: Intent-to-treat analyses showed
      that IG participants showed significant improvement in HbA1c (-0.57%/6.2 mmol/mol
      vs. +0.36%/3.9 mmol/mol, P = 0.01), diabetes-related QOL (+0.7 vs. +0.15, P =
      0.04), and habit strength for checking blood glucose (+3.9 vs. +1.7, P = 0.05) as
      compared with CG participants. There was no statistically significant effect
      modification by sex, ethnicity, diabetes type, recruitment site, or SES. No study
      related serious adverse events were reported. CONCLUSIONS: The REAL Diabetes
      intervention improved blood glucose control and diabetes-related QOL among a
      typically hard-to-reach population, thus providing evidence that a structured OT
      intervention may be beneficial in improving both clinical and psychosocial
      outcomes among individuals with diabetes.

PMID- 29351963
TI  - The exon junction complex: structural insights into a faithful companion of
      mammalian mRNPs.
AB  - During splicing, the exon junction complex (EJC) is deposited upstream of exon
      exon boundaries. The EJC and its peripheral bound proteins play an essential role
      in mediating mRNA export, translation and turnover. However, the exact sequence
      of EJC assembly and the involved factors during splicing remain elusive. Recently
      published structures of the human C* spliceosome clarified the position of the
      EJC at this phase of splicing and have given insight into previously unidentified
      interactions between the EJC and spliceosomal proteins. Here, these new
      observations are presented and the significance for EJC assembly is discussed.
      Furthermore, the vast landscape of EJC interacting proteins and their manifold
      functions are described. Finally, the factors involved in EJC disassembly and
      recycling are recapitulated. This review aims to integrate structural,
      biochemical and physiological data to obtain a comprehensive picture of EJC
      components during the lifetime of the EJC.

PMID- 29351964
TI  - Chitinase-like proteins as regulators of innate immunity and tissue repair:
      helpful lessons for asthma?
AB  - Chitinases and chitinase-like proteins (CLPs) belong to the glycoside hydrolase
      family 18 of proteins. Chitinases are expressed in mammals and lower organisms,
      facilitate chitin degradation, and hence act as host-defence enzymes. Gene
      duplication and loss-of-function mutations of enzymatically active chitinases
      have resulted in the expression of a diverse range of CLPs across different
      species. CLPs are genes that are increasingly associated with inflammation and
      tissue remodelling not only in mammals but also across distant species. While the
      focus has remained on understanding the functions and expression patterns of CLPs
      during disease in humans, studies in mouse and lower organisms have revealed
      important and overlapping roles of the CLP family during physiology, host defence
      and pathology. This review will summarise recent insights into the regulatory
      functions of CLPs on innate immune pathways and discuss how these effects are not
      only important for host defence and tissue injury/repair after pathogen invasion,
      but also how they have extensive implications for pathological processes involved
      in diseases such as asthma.

PMID- 29351962
TI  - RNA helicases in RNA decay.
AB  - RNA molecules have the tendency to fold into complex structures or to associate
      with complementary RNAs that exoribonucleases have difficulties processing or
      degrading. Therefore, degradosomes in bacteria and organelles as well as exosomes
      in eukaryotes have teamed-up with RNA helicases. Whereas bacterial degradosomes
      are associated with RNA helicases from the DEAD-box family, the exosomes and
      mitochondrial degradosome use the help of Ski2-like and Suv3 RNA helicases.

PMID- 29351965
TI  - Cost-effectiveness of Cognitive Behavioral Therapy for Depressed Youth Declining
      Antidepressants.
AB  - BACKGROUND AND OBJECTIVES: Adolescents with depression identified in primary care
      settings often have limited treatment options beyond antidepressant (AD) therapy.
      We assessed the cost-effectiveness of a brief cognitive behavioral therapy (CBT)
      program among depressed adolescents who declined or quickly stopped using ADs.
      METHODS: A total of 212 youth with depression were randomly assigned to treatment
      as usual (TAU) or TAU plus brief individual CBT. Clinical outcomes included
      depression-free days (DFDs) and estimated quality-adjusted life-years (QALYs).
      Costs were adjusted to 2008 US dollars. Incremental cost-effectiveness ratios
      (ICERs) comparing CBT to TAU were calculated over 12- and 24-month follow-up
      periods. RESULTS: Youth randomly assigned to CBT had 26.8 more DFDs (P = .044)
      and 0.067 more QALYs (P = .044) on average compared with TAU over 12 months.
      Total costs were $4976 less (P = .025) by the end of the 24-month follow-up among
      youth randomly assigned to CBT. Total costs per DFD were -$51 (ICER = -$51; 95%
      confidence interval [CI]: -$394 to $9) at 12 months and -$115 (ICER = -$115; 95%
      CI: -$1090 to -$6) at 24 months. Total costs per QALY were -$20 282 (ICER = -$20
      282; 95% CI: -$156 741 to $3617) at 12 months and -$45 792 (ICER = -$45 792; 95%
      CI: -$440 991 to -$2731) at 24 months. CONCLUSIONS: Brief primary care CBT among
      youth declining AD therapy is cost-effective by widely accepted standards in
      depression treatment. CBT becomes dominant over TAU over time, as revealed by a
      statistically significant cost offset at the end of the 2-year follow-up.

PMID- 29351967
TI  - Veterinary salaries in the UK are stagnating or in decline, surveys show.

PMID- 29351966
TI  - Why are vet salaries so stubbornly flat?

PMID- 29351969
TI  - Avian influenza cases confirmed in Dorset.

PMID- 29351970
TI  - Government pledges to reduce the ocean's plastic.
AB  - Georgina Mills explains how prime minister Theresa May has committed to reducing
      the UK's plastic waste, in a bid to save the world's marine wildlife.

PMID- 29351972
TI  - Cobalt deficiency in illthriven lambs.

PMID- 29351973
TI  - Claw condition and claw health in dairy cows: how important is access to pasture?

PMID- 29351975
TI  - Porcine circovirus type 3: a threat to the pig industry?

PMID- 29351976
TI  - Being your own vet.

PMID- 29351977
TI  - Unanticipated hyperkalaemia.

PMID- 29351978
TI  - Death notice.

PMID- 29351979
TI  - When is the right time?
AB  - Veterinary medicine is veering further towards prolongation of life at all costs,
      without the safeguard of being able to robustly measure quality of life. Jacky
      Reid, Andrea Nolan and Marian Scott discuss major steps forward in the ability to
      measure changes in health-related quality of life.

PMID- 29351980
TI  - How to improve your salary.

PMID- 29351983
TI  - Partial tandem duplication of KMT2A (MLL) may predict a subset of myelodysplastic
      syndrome with unique characteristics and poor outcome.

PMID- 29351984
TI  - Venetoclax induced a complete response in a patient with immunoglobulin light
      chain amyloidosis plateaued on cyclophosphamide, bortezomib and dexamethasone.

PMID- 29351982
TI  - Prevalence and characteristics of metabolic syndrome in adults from the French
      childhood leukemia survivors' cohort: a comparison with controls from the French
      population.
AB  - The prevalence of the metabolic syndrome among adults from the French LEA
      childhood acute leukemia survivors' cohort was prospectively evaluated
      considering the type of anti-leukemic treatment received, and compared with that
      of controls. The metabolic profile of these patients was compared with that of
      controls. A total of 3203 patients from a French volunteer cohort were age- and
      sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4
      years; females: 51%). Metabolic syndrome was defined according to the National
      Cholesterol Education Program's Adult Treatment Panel III criteria. Metabolic
      syndrome was found in 10.3% of patients (mean follow-up duration: 16.3+/-0.2
      years) and 4.5% of controls, (OR=2.49; P<0.001). Patients transplanted with total
      body irradiation presented the highest risk (OR=6.26; P<0.001); the other
      treatment groups also showed a higher risk than controls, including patients
      treated with chemotherapy only. Odd Ratios were 1.68 (P=0.005) after chemotherapy
      only, 2.32 (P=0.002) after chemotherapy and cranial irradiation, and 2.18
      (P=0.057) in patients transplanted without irradiation. Total body irradiation
      recipients with metabolic syndrome displayed a unique profile compared with
      controls: smaller waist circumference (91 vs 99.6 cm; P=0.01), and increased
      triglyceride levels (3.99 vs 1.5 mmol/L; P<0.001), fasting glucose levels (6.2 vs
      5.6 mmol/L; P=0.049), and systolic blood pressure (137.9 vs 132.8 mmHg; P=0.005).
      By contrast, cranial irradiation recipients with metabolic syndrome had a larger
      waist circumference (109 vs 99.6 cm; P=0.007) than controls. Regardless of the
      anti-leukemic treatment, metabolic syndrome risk was higher among childhood
      leukemia survivors. Its presentation differed depending on the treatment type,
      thus suggesting a divergent pathophysiology. This study is registered at
      clinicaltrials.gov identifier: 01756599.

PMID- 29351985
TI  - Tocilizumab, tacrolimus and methotrexate for the prevention of acute graft-versus
      host disease: low incidence of lower gastrointestinal tract disease.
AB  - We conducted a phase 2 study in which patients undergoing allogeneic
      hematopoietic stem cell transplantation received tocilizumab in addition to
      standard immune suppression with tacrolimus and methotrexate for graft-versus
      host disease prophylaxis. Thirty-five patients were enrolled between January 2015
      and June 2016. The median age of the cohort was 66 (range: 22-76). All patients
      received busulfan-based conditioning, and were transplanted with human leukocyte
      antigen-matched related or matched unrelated bone marrow or peripheral stem cell
      grafts. The cumulative incidences of grades II-IV and III-IV acute graft-versus
      host disease were 14% (95% CI 5-30) and 3% (95% CI 0-11) at day 100, and 17% (95%
      CI 7-31) and 6% (95% CI 1-16) at day 180, respectively. Notably, there were no
      cases of graft-versus-host disease of the lower gastrointestinal tract within the
      first 100 days. A comparison to 130 matched controls who only received tacrolimus
      and methotrexate demonstrated a lower cumulative incidence of grades II-IV acute
      graft-versus-host disease (17% versus 45%, P=0.003) and a significant increase in
      grades II-IV acute graft-versus-host disease-free survival at six months (69%
      versus 42%, P=0.001) with tocilizumab, tacrolimus and methotrexate, which was the
      primary endpoint of the study. Immune reconstitution was preserved in patients
      treated with tocilizumab, tacrolimus and methotrexate, as T-cell and B-cell
      subsets recovered to near normal levels by 6-12 months post-transplantation. We
      conclude that tocilizumab has promising activity in preventing acute graft-versus
      host disease, particularly in the lower gastrointestinal tract, and warrants
      examination in a randomized setting.

PMID- 29351986
TI  - A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced
      relapsed/refractory Hodgkin lymphoma.
AB  - JAK2 constitutive activation/overexpression is common in classical Hodgkin
      lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing
      JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial
      in Hodgkin lymphoma. In this phase II study we assessed the safety and efficacy
      of ruxolitinib, an oral JAK1/2 inhibitor, in patients with relapsed/refractory
      Hodgkin lymphoma. The primary objective was overall response rate according to
      the International Harmonization Project 2007 criteria. Thirty-three patients with
      advanced disease (median number of prior lines of treatment: 5; refractory: 82%)
      were included; nine (27.3%) received at least six cycles of ruxolitinib and six
      (18.2%) received more than six cycles. The overall response rate after six cycles
      was 9.4% (3/32 patients). All three responders had partial responses; another 11
      patients had transient stable disease. Best overall response rate was 18.8% (6/32
      patients). Rapid alleviation of B-symptoms was common. The median duration of
      response was 7.7 months, median progression-free survival 3.5 months (95% CI: 1.9
      4.6), and the median overall survival 27.1 months (95% CI: 14.4-27.1). Forty
      adverse events were reported in 14/33 patients (42.4%). One event led to
      treatment discontinuation, while 87.5% of patients recovered without sequelae.
      Twenty-five adverse events were grade 3 or higher. These events were mostly
      anemia (n=11), all considered related to ruxolitinib. Other main causes of grade
      3 or higher adverse events included lymphopenia and infections. Of note, no cases
      of grade 4 neutropenia or thrombocytopenia were observed. Ruxolitinib shows signs
      of activity, albeit short-lived, beyond a simple anti-inflammatory effect. Its
      limited toxicity suggests that it has the potential to be combined with other
      therapeutic modalities. ClinicalTrials.gov: NCT01877005.

PMID- 29351987
TI  - CD83 is a new potential biomarker and therapeutic target for Hodgkin lymphoma.
AB  - Chemotherapy and hematopoietic stem cell transplantation are effective treatments
      for most Hodgkin lymphoma patients, however there remains a need for better tumor
      specific target therapy in Hodgkin lymphoma patients with refractory or relapsed
      disease. Herein, we demonstrate that membrane CD83 is a diagnostic and
      therapeutic target, highly expressed in Hodgkin lymphoma cell lines and Hodgkin
      and Reed-Sternberg cells in 29/35 (82.9%) Hodgkin lymphoma patient lymph node
      biopsies. CD83 from Hodgkin lymphoma tumor cells was able to trogocytose to
      surrounding T cells and, interestingly, the trogocytosing CD83+T cells expressed
      significantly more programmed death-1 compared to CD83-T cells. Hodgkin lymphoma
      tumor cells secreted soluble CD83 that inhibited T-cell proliferation, and anti
      CD83 antibody partially reversed the inhibitory effect. High levels of soluble
      CD83 were detected in Hodgkin lymphoma patient sera, which returned to normal in
      patients who had good clinical responses to chemotherapy confirmed by positron
      emission tomography scans. We generated a human anti-human CD83 antibody, 3C12C,
      and its toxin monomethyl auristatin E conjugate, that killed CD83 positive
      Hodgkin lymphoma cells but not CD83 negative cells. The 3C12C antibody was tested
      in dose escalation studies in non-human primates. No toxicity was observed, but
      there was evidence of CD83 positive target cell depletion. These data establish
      CD83 as a potential biomarker and therapeutic target in Hodgkin lymphoma.

PMID- 29351988
TI  - Confirmation of intersubunit connectivity and topology of designed protein
      complexes by native MS.
AB  - Computational protein design provides the tools to expand the diversity of
      protein complexes beyond those found in nature. Understanding the rules that
      drive proteins to interact with each other enables the design of protein-protein
      interactions to generate specific protein assemblies. In this work, we designed
      protein-protein interfaces between dimers and trimers to generate dodecameric
      protein assemblies with dihedral point group symmetry. We subsequently analyzed
      the designed protein complexes by native MS. We show that the use of ion mobility
      MS in combination with surface-induced dissociation (SID) allows for the rapid
      determination of the stoichiometry and topology of designed complexes. The
      information collected along with the speed of data acquisition and processing
      make SID ion mobility MS well-suited to determine key structural features of
      designed protein complexes, thereby circumventing the requirement for more time-
      and sample-consuming structural biology approaches.

PMID- 29351989
TI  - Iterative random forests to discover predictive and stable high-order
      interactions.
AB  - Genomics has revolutionized biology, enabling the interrogation of whole
      transcriptomes, genome-wide binding sites for proteins, and many other molecular
      processes. However, individual genomic assays measure elements that interact in
      vivo as components of larger molecular machines. Understanding how these high
      order interactions drive gene expression presents a substantial statistical
      challenge. Building on random forests (RFs) and random intersection trees (RITs)
      and through extensive, biologically inspired simulations, we developed the
      iterative random forest algorithm (iRF). iRF trains a feature-weighted ensemble
      of decision trees to detect stable, high-order interactions with the same order
      of computational cost as the RF. We demonstrate the utility of iRF for high-order
      interaction discovery in two prediction problems: enhancer activity in the early
      Drosophila embryo and alternative splicing of primary transcripts in human
      derived cell lines. In Drosophila, among the 20 pairwise transcription factor
      interactions iRF identifies as stable (returned in more than half of bootstrap
      replicates), 80% have been previously reported as physical interactions.
      Moreover, third-order interactions, e.g., between Zelda (Zld), Giant (Gt), and
      Twist (Twi), suggest high-order relationships that are candidates for follow-up
      experiments. In human-derived cells, iRF rediscovered a central role of H3K36me3
      in chromatin-mediated splicing regulation and identified interesting fifth- and
      sixth-order interactions, indicative of multivalent nucleosomes with specific
      roles in splicing regulation. By decoupling the order of interactions from the
      computational cost of identification, iRF opens additional avenues of inquiry
      into the molecular mechanisms underlying genome biology.

PMID- 29351990
TI  - Saa3 is a key mediator of the protumorigenic properties of cancer-associated
      fibroblasts in pancreatic tumors.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of
      abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts
      (CAFs). It is generally accepted that CAFs stimulate tumor progression and might
      be implicated in drug resistance and immunosuppression. Here, we have compared
      the transcriptional profile of PDGFRalpha+ CAFs isolated from genetically
      engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to
      identify genes potentially implicated in their protumorigenic properties. We
      report that the most differentially expressed gene, Saa3, a member of the serum
      amyloid A (SAA) apolipoprotein family, is a key mediator of the protumorigenic
      activity of PDGFRalpha+ CAFs. Whereas Saa3-competent CAFs stimulate the growth of
      tumor cells in an orthotopic model, Saa3-null CAFs inhibit tumor growth. Saa3
      also plays a role in the cross talk between CAFs and tumor cells. Ablation of
      Saa3 in pancreatic tumor cells makes them insensitive to the inhibitory effect of
      Saa3-null CAFs. As a consequence, germline ablation of Saa3 does not prevent PDAC
      development in mice. The protumorigenic activity of Saa3 in CAFs is mediated by
      Mpp6, a member of the palmitoylated membrane protein subfamily of the peripheral
      membrane-associated guanylate kinases (MAGUK). Finally, we interrogated whether
      these observations could be translated to a human scenario. Indeed, SAA1, the
      ortholog of murine Saa3, is overexpressed in human CAFs. Moreover, high levels of
      SAA1 in the stromal component correlate with worse survival. These findings
      support the concept that selective inhibition of SAA1 in CAFs may provide
      potential therapeutic benefit to PDAC patients.

PMID- 29351991
TI  - Differing roles of CD1d2 and CD1d1 proteins in type I natural killer T cell
      development and function.
AB  - MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T
      cells. Differences in the antigen-binding clefts of the CD1 family members
      determine the conformation and size of the lipids that are presented, although
      the factors that shape CD1 diversity remain unclear. In mice, two homologous
      genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the
      development and function of natural killer T (NKT) cells. However, it remains
      unclear whether both CD1d isoforms are equivalent in their antigen presentation
      capacity and functions. Here, we report that CD1d2 molecules are expressed in the
      thymus of some mouse strains, where they select functional type I NKT cells.
      Intriguingly, the T cell antigen receptor repertoire and phenotype of CD1d2
      selected type I NKT cells in CD1D1-/- mice differed from CD1d1-selected type I
      NKT cells. The structures of CD1d2 in complex with endogenous lipids and a
      truncated acyl-chain analog of alpha-galactosylceramide revealed that its A'
      pocket was restricted in size compared with CD1d1. Accordingly, CD1d2 molecules
      could not present glycolipid antigens with long acyl chains efficiently, favoring
      the presentation of short acyl chain antigens. These results indicate that the
      two CD1d molecules present different sets of self-antigen(s) in the mouse thymus,
      thereby impacting the development of invariant NKT cells.

PMID- 29351992
TI  - Involvement of Aryl hydrocarbon receptor in myelination and in human nerve sheath
      tumorigenesis.
AB  - Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor
      involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform
      into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to
      existing therapies. These tumors are primarily composed of Schwann cells. In
      addition to neurofibromatosis type 1 (NF1) gene inactivation, further genetic
      lesions are required for malignant transformation. We have quantified the mRNA
      expression levels of AHR and its associated genes in 38 human samples. We report
      that AHR and the biosynthetic enzymes of its endogenous ligand are overexpressed
      in human biopsies of PNFs and MPNSTs. We also detect a strong nuclear AHR
      staining in MPNSTs. The inhibition of AHR by siRNA or antagonists, CH-223191 and
      trimethoxyflavone, induces apoptosis in human MPNST cells. Since AHR
      dysregulation is observed in these tumors, we investigate AHR involvement in
      Schwann cell physiology. Hence, we studied the role of AHR in myelin structure
      and myelin gene regulation in Ahr-/- mice during myelin development. AHR ablation
      leads to locomotion defects and provokes thinner myelin sheaths around the axons.
      We observe a dysregulation of myelin gene expression and myelin developmental
      markers in Ahr-/- mice. Interestingly, AHR does not directly bind to myelin gene
      promoters. The inhibition of AHR in vitro and in vivo increased beta-catenin
      levels and stimulated the binding of beta-catenin on myelin gene promoters. Taken
      together, our findings reveal an endogenous role of AHR in peripheral myelination
      and in peripheral nerve sheath tumors. Finally, we suggest a potential
      therapeutic approach by targeting AHR in nerve tumors.

PMID- 29351993
TI  - Fluorine-donating electrolytes enable highly reversible 5-V-class Li metal
      batteries.
AB  - Lithium metal has gravimetric capacity ~10* that of graphite which incentivizes
      rechargeable Li metal batteries (RLMB) development. A key factor that limits
      practical use of RLMB is morphological instability of Li metal anode upon
      electrodeposition, reflected by the uncontrolled area growth of solid-electrolyte
      interphase that traps cyclable Li, quantified by the Coulombic inefficiency (CI).
      Here we show that CI decreases approximately exponentially with increasing
      donatable fluorine concentration of the electrolyte. By using up to 7 m of Li
      bis(fluorosulfonyl)imide in fluoroethylene carbonate, where both the solvent and
      the salt donate F, we can significantly suppress anode porosity and improve the
      Coulombic efficiency to 99.64%. The electrolyte demonstrates excellent
      compatibility with 5-V LiNi0.5Mn1.5O4 cathode and Al current collector beyond 5
      V. As a result, an RLMB full cell with only 1.4* excess lithium as the anode was
      demonstrated to cycle above 130 times, at industrially significant loading of
      1.83 mAh/cm2 and 0.36 C. This is attributed to the formation of a protective LiF
      nanolayer, which has a wide bandgap, high surface energy, and small Burgers
      vector, making it ductile at room temperature and less likely to rupture in
      electrodeposition.

PMID- 29351994
TI  - Full molecular trajectories of RNA polymerase at single base-pair resolution.
AB  - In recent years, highly stable optical tweezers systems have enabled the
      characterization of the dynamics of molecular motors at very high resolution.
      However, the motion of many motors with angstrom-scale dynamics cannot be
      consistently resolved due to poor signal-to-noise ratio. Using an acousto-optic
      deflector to generate a "time-shared" dual-optical trap, we decreased low
      frequency noise by more than one order of magnitude compared with conventional
      dual-trap optical tweezers. Using this instrument, we implemented a protocol that
      synthesizes single base-pair trajectories, which are used to test a Large State
      Space Hidden Markov Model algorithm to recover their individual steps. We then
      used this algorithm on real transcription data obtained in the same instrument to
      fully uncover the molecular trajectories of Escherichia coli RNA polymerase. We
      applied this procedure to reveal the effect of pyrophosphate on the distribution
      of dwell times between consecutive polymerase steps.

PMID- 29351995
TI  - Enucleated cells reveal differential roles of the nucleus in cell migration,
      polarity, and mechanotransduction.
AB  - The nucleus has long been postulated to play a critical physical role during cell
      polarization and migration, but that role has not been defined or rigorously
      tested. Here, we enucleated cells to test the physical necessity of the nucleus
      during cell polarization and directed migration. Using enucleated mammalian cells
      (cytoplasts), we found that polarity establishment and cell migration in one
      dimension (1D) and two dimensions (2D) occur without the nucleus. Cytoplasts
      directionally migrate toward soluble (chemotaxis) and surface-bound (haptotaxis)
      extracellular cues and migrate collectively in scratch-wound assays. Consistent
      with previous studies, migration in 3D environments was dependent on the nucleus.
      In part, this likely reflects the decreased force exerted by cytoplasts on
      mechanically compliant substrates. This response is mimicked both in cells with
      nucleocytoskeletal defects and upon inhibition of actomyosin-based contractility.
      Together, our observations reveal that the nucleus is dispensable for
      polarization and migration in 1D and 2D but critical for proper cell mechanical
      responses.

PMID- 29351997
TI  - Spatiotemporal organization of exocytosis emerges during neuronal shape change.
AB  - Neurite elongation and branching in developing neurons requires plasmalemma
      expansion, hypothesized to occur primarily via exocytosis. We posited that
      exocytosis in developing neurons and nonneuronal cells would exhibit distinct
      spatiotemporal organization. We exploited total internal reflection fluorescence
      microscopy to image vesicle-associated membrane protein (VAMP)-pHluorin-mediated
      exocytosis in mouse embryonic cortical neurons and interphase melanoma cells, and
      developed computer-vision software and statistical tools to uncover
      spatiotemporal aspects of exocytosis. Vesicle fusion behavior differed between
      vesicle types, cell types, developmental stages, and extracellular environments.
      Experiment-based mathematical calculations indicated that VAMP2-mediated vesicle
      fusion supplied excess material for the plasma membrane expansion that occurred
      early in neuronal morphogenesis, which was balanced by clathrin-mediated
      endocytosis. Spatial statistics uncovered distinct spatiotemporal regulation of
      exocytosis in the soma and neurites of developing neurons that was modulated by
      developmental stage, exposure to the guidance cue netrin-1, and the brain
      enriched ubiquitin ligase tripartite motif 9. In melanoma cells, exocytosis
      occurred less frequently, with distinct spatial clustering patterns.

PMID- 29351996
TI  - Altered chemomechanical coupling causes impaired motility of the kinesin-4 motors
      KIF27 and KIF7.
AB  - Kinesin-4 motors play important roles in cell division, microtubule organization,
      and signaling. Understanding how motors perform their functions requires an
      understanding of their mechanochemical and motility properties. We demonstrate
      that KIF27 can influence microtubule dynamics, suggesting a conserved function in
      microtubule organization across the kinesin-4 family. However, kinesin-4 motors
      display dramatically different motility characteristics: KIF4 and KIF21 motors
      are fast and processive, KIF7 and its Drosophila melanogaster homologue Costal2
      (Cos2) are immotile, and KIF27 is slow and processive. Neither KIF7 nor KIF27 can
      cooperate for fast processive transport when working in teams. The mechanistic
      basis of immotile KIF7 behavior arises from an inability to release adenosine
      diphosphate in response to microtubule binding, whereas slow processive KIF27
      behavior arises from a slow adenosine triphosphatase rate and a high affinity for
      both adenosine triphosphate and microtubules. We suggest that evolutionarily
      selected sequence differences enable immotile KIF7 and Cos2 motors to function
      not as transporters but as microtubule-based tethers of signaling complexes.

PMID- 29351999
TI  - MLL1 Promotes IL-7 Responsiveness and Survival during B Cell Differentiation.
AB  - B lymphocyte differentiation is an exquisitely regulated homeostatic process
      resulting in continuous production of appropriately selected B cells. Relatively
      small changes in gene expression can result in deregulation of this process,
      leading to acute lymphocytic leukemia (ALL), immune deficiency, or autoimmunity.
      Translocation of MLL1 (KMT2A) often results in a pro-B cell ALL, but little is
      known about its role in normal B cell differentiation. Using a Rag1-cre mouse
      knock-in to selectively delete Mll1 in developing lymphocytes, we show that B
      cell, but not T cell, homeostasis depends on MLL1. Mll1-/- B progenitors fail to
      differentiate efficiently through the pro- to pre-B cell transition, resulting in
      a persistent reduction in B cell populations. Cells inefficiently transit the pre
      BCR checkpoint, despite normal to higher levels of pre-BCR components, and
      rearranged IgH expression fails to rescue this differentiation block. Instead of
      IgH-rearrangement defects, we find that Mll1-/- pre-B cells exhibit attenuated
      RAS/MAPK signaling downstream of the pre-BCR, which results in reduced survival
      in physiologic levels of IL-7. Genome-wide expression data illustrate that MLL1
      is connected to B cell differentiation and IL-7-dependent survival through a
      complex transcriptional network. Overall, our data demonstrate that wild-type
      MLL1 is a regulator of pre-BCR signaling and B cell differentiation and further
      suggest that targeting its function in pro-B cell ALL may be more broadly
      effective than previously anticipated.

PMID- 29351998
TI  - Detection of Experimental and Clinical Immune Complexes by Measuring SHIP-1
      Recruitment to the Inhibitory FcgammaRIIB.
AB  - Fc gamma receptors (FcgammaR) are involved in multiple aspects of immune cell
      regulation, are central to the success of mAb therapeutics, and underpin the
      pathology of several autoimmune diseases. However, reliable assays capable of
      accurately measuring FcgammaR interactions with their physiological ligands, IgG
      immune complexes (IC), are limited. A method to study and detect IC interactions
      with FcgammaRs was therefore developed. This method, designed to model the
      signaling pathway of the inhibitory FcgammaRIIB (CD32B), used NanoLuc Binary
      Interaction Technology to measure recruitment of the Src homology 2 domain
      containing inositol phosphatase 1 to the ITIM of this receptor. Such recruitment
      required prior cross-linking of an ITAM-containing activatory receptor, and
      evoked luciferase activity in discrete clusters at the cell surface,
      recapitulating the known biology of CD32B signaling. The assay detected varying
      forms of experimental IC, including heat-aggregated IgG, rituximab-anti-idiotype
      complexes, and anti-trinitrophenol-trinitrophenol complexes in a sensitive manner
      (<=1 MUg/ml), and discriminated between complexes of varying size and isotype.
      Proof-of-concept for the detection of circulating ICs in autoimmune disease was
      provided, as responses to sera from patients with systemic lupus erythematosus
      and rheumatoid arthritis were detected in small pilot studies. Finally, the
      method was translated to a stable cell line system. In conclusion, a rapid and
      robust method for the detection of IC was developed, which has numerous potential
      applications including the monitoring of IC in autoimmune diseases and the study
      of underlying FcgammaR biology.

PMID- 29352000
TI  - Mesenchymal Stem Cells Recruit CCR2+ Monocytes To Suppress Allergic Airway
      Inflammation.
AB  - Mesenchymal stem cells (MSC) exert immune modulatory properties and previous
      studies demonstrated suppressive effects of MSC treatment in animal models of
      allergic airway inflammation. However, the underlying mechanisms have not been
      fully elucidated. We studied the role of MSC in immune activation and subsequent
      recruitment of monocytes in suppressing airway hyperresponsiveness and airway
      inflammation using a mouse model of allergic airway inflammation. MSC
      administration prior to or after allergen challenge inhibited the development of
      airway inflammation in allergen-sensitized mice. This was accompanied by an
      influx of CCR2-positive monocytes, which were localized around injected MSC in
      the lungs. Notably, IL-10-producing monocytes and/or macrophages were also
      increased in the lungs. Systemic administration of liposomal clodronate or a CCR2
      antagonist significantly prevented the suppressive effects of MSC. Activation of
      MSC by IFN-gamma leading to the upregulation of CCL2 expression was essential for
      the suppressive effects, as administration of wild-type MSC into IFN-gamma
      deficient recipients, or IFN-gamma receptor-deficient or CCL2-deficient MSC into
      wild-type mice failed to suppress airway inflammation. These results suggest that
      MSC activation by IFN-gamma, followed by increased expression of CCL2 and
      recruitment of monocytes to the lungs, is essential for suppression by MSC in
      allergen-induced airway hyperresponsiveness and airway inflammation.

PMID- 29352001
TI  - KEAP1 Editing Using CRISPR/Cas9 for Therapeutic NRF2 Activation in Primary Human
      T Lymphocytes.
AB  - Oxidant stress modifies T lymphocyte activation and function. Previous work
      demonstrated that murine T cell-specific kelch like-ECH-associated protein 1
      (Keap1) deletion enhances antioxidant capacity and protects from experimental
      acute kidney injury. In this study, we used CRISPR technology to develop
      clinically translatable human T cell-specific KEAP1 deletion. Delivery of KEAP1
      exon 2 specific Cas9:guide RNA in Jurkat T cells led to significant (~70%)
      editing and upregulation of NRF2-regulated antioxidant genes NADPH dehydrogenase
      quinone 1 (NQO1) (up to 11-fold), heme oxygenase 1 (HO1) (up to 11-fold), and
      GCLM (up to 2-fold). In primary human T cells, delivery of KEAP1 exon 2 target
      site 2-specific ATTO 550-labeled Cas9:guide RNA edited KEAP1 in ~40% cells and
      significantly (p <= 0.04) increased NQO1 (16-fold), HO1 (9-fold), and GCLM (2
      fold) expression. To further enrich KEAP1-edited cells, ATTO 550-positive cells
      were sorted 24 h after electroporation. Assessment of ATTO 550-positive cells
      showed KEAP1 editing in ~55% cells. There was no detectable off-target cleavage
      in the top three predicted genes in the ATTO 550-positive cells. Gene expression
      analysis found significantly (p <= 0.01) higher expression of NQO1 mRNA in ATTO
      550-positive cells compared with control cells. Flow cytometric assessment showed
      increased (p <= 0.01) frequency of CD4-, CD25-, and CD69-expressing KEAP1 edited
      cells whereas frequency of CD8- (p <= 0.01) and IL-17- (p <= 0.05) expressing
      cells was reduced compared with control cells. Similar experimental conditions
      resulted in significant KEAP1 editing, increased antioxidant gene expression, and
      frequency of CD69 and IL-10 positive cells in highly enriched KEAP1-edited
      regulatory T cells. KEAP1-edited T cells could potentially be used for treating
      multiple human diseases.

PMID- 29352002
TI  - Intestinal Epithelial Cell-Derived LKB1 Suppresses Colitogenic Microbiota.
AB  - Dysregulation of the immune barrier function of the intestinal epithelium can
      often result in dysbiosis. In this study we report a novel role of intestinal
      epithelial cell (IEC)-derived liver kinase B1 (LKB1) in suppressing colitogenic
      microbiota. IEC-specific deletion of LKB1 (LKB1DeltaIEC) resulted in an increased
      susceptibility to dextran sodium sulfate (DSS)-induced colitis and a definitive
      shift in the composition of the microbial population in the mouse intestine.
      Importantly, transfer of the microbiota from LKB1DeltaIEC mice was sufficient to
      confer increased susceptibility to DSS-induced colitis in wild-type recipient
      mice. Collectively, the data indicate that LKB1 deficiency in intestinal
      epithelial cells nurtures the outgrowth of colitogenic bacteria in the commensal
      community. In addition, LKB1 deficiency in the intestinal epithelium reduced the
      production of IL-18 and antimicrobial peptides in the colon. Administration of
      exogenous IL-18 restored the expression of antimicrobial peptides, corrected the
      outgrowth of several bacterial genera, and rescued the LKB1DeltaIEC mice from
      increased sensitivity to DSS challenge. Taken together, our study reveals an
      important function of LKB1 in IECs for suppressing colitogenic microbiota by IL
      18 expression.

PMID- 29352004
TI  - Therapeutic Application of an Extract of Helicobacter pylori Ameliorates the
      Development of Allergic Airway Disease.
AB  - Epidemiological and experimental studies have shown that exposure to the gastric
      bacterium Helicobacter pylori, especially in early life, prevents the development
      of asthma. Recent mouse studies have shown that this protective effect does not
      require live bacteria and that treatment with an extract of H. pylori in neonates
      prevents the development of airway inflammation and goblet cell metaplasia. In
      the current study, the effect of administration of an extract of H. pylori was
      assessed in a therapeutic study design with application of the extract just prior
      to allergen challenge. C57BL/6 mice were sensitized and challenged with OVA or
      house dust mite. Treatment with H. pylori extract just prior to the challenge
      significantly reduced airway inflammation, as assessed in bronchoalveolar lavage
      fluid and lung tissue, and reduced airway remodeling, as assessed by goblet cell
      quantification. These effects were apparent in the OVA model and in the house
      dust mite model. Injection of H. pylori extract reduced the processing of
      allergen by dendritic cells in the lungs and mediastinal lymph node. Bone marrow
      derived dendritic cells exposed to H. pylori extract were affected with regard to
      their ability to process Ag. These data show that application of H. pylori
      extract after sensitization effectively inhibits allergic airway disease.

PMID- 29352003
TI  - Gene Expression Signatures Characterized by Longitudinal Stability and
      Interindividual Variability Delineate Baseline Phenotypic Groups with Distinct
      Responses to Immune Stimulation.
AB  - Human immunity exhibits remarkable heterogeneity among individuals, which
      engenders variable responses to immune perturbations in human populations.
      Population studies reveal that, in addition to interindividual heterogeneity,
      systemic immune signatures display longitudinal stability within individuals, and
      these signatures may reliably dictate how given individuals respond to immune
      perturbations. We hypothesize that analyzing relationships among these signatures
      at the population level may uncover baseline immune phenotypes that correspond
      with response outcomes to immune stimuli. To test this, we quantified global gene
      expression in peripheral blood CD4+ cells from healthy individuals at baseline
      and following CD3/CD28 stimulation at two time points 1 mo apart. Systemic CD4+
      cell baseline and poststimulation molecular immune response signatures (MIRS)
      were defined by identifying genes expressed at levels that were stable between
      time points within individuals and differential among individuals in each state.
      Iterative differential gene expression analyses between all possible phenotypic
      groupings of at least three individuals using the baseline and stimulated MIRS
      gene sets revealed shared baseline and response phenotypic groupings, indicating
      the baseline MIRS contained determinants of immune responsiveness. Furthermore,
      significant numbers of shared phenotype-defining sets of determinants were
      identified in baseline data across independent healthy cohorts. Combining the
      cohorts and repeating the analyses resulted in identification of over 6000
      baseline immune phenotypic groups, implying that the MIRS concept may be useful
      in many immune perturbation contexts. These findings demonstrate that patterns in
      complex gene expression variability can be used to define immune phenotypes and
      discover determinants of immune responsiveness.

PMID- 29352005
TI  - Differential Expression of CD8+ T Cell Cytotoxic Effector Molecules in Blood and
      Gastrointestinal Mucosa in HIV-1 Infection.
AB  - We previously reported that CD8+ T cells in human gastrointestinal mucosa exhibit
      reduced perforin expression and weak or impaired cytotoxic capacity compared with
      their counterparts in blood. Nevertheless, these cells degranulate and express
      cytokines and chemokines in response to cognate Ag. In addition to weak
      expression of perforin, earlier studies suggested differential regulation of
      perforin and granzymes (Gzms), with GzmA and B expressed by significantly higher
      percentages of mucosal CD8+ T cells than perforin. However, this topic has not
      been fully explored. The goal of this study was to elucidate the expression and
      coexpression patterns of GzmA, B, and K in conjunction with perforin in
      rectosigmoid CD8+ T cells during HIV-1 infection. We found that expression of
      both perforin and GzmB, but not GzmA or GzmK, was reduced in mucosa compared with
      blood. A large fraction of rectosigmoid CD8+ T cells either did not express Gzms
      or were single-positive for GzmA. Rectosigmoid CD8+ T cells appeared skewed
      toward cytokine production rather than cytotoxic responses, with cells expressing
      multiple cytokines and chemokines generally lacking in perforin and Gzm
      expression. These data support the interpretation that perforin and Gzms are
      differentially regulated, and display distinct expression patterns in blood and
      rectosigmoid T cells. These studies may help inform the development of strategies
      to combat HIV-1 and other mucosal pathogens.

PMID- 29352006
TI  - Machine learning in cardiovascular medicine: are we there yet?
AB  - Artificial intelligence (AI) broadly refers to analytical algorithms that
      iteratively learn from data, allowing computers to find hidden insights without
      being explicitly programmed where to look. These include a family of operations
      encompassing several terms like machine learning, cognitive learning, deep
      learning and reinforcement learning-based methods that can be used to integrate
      and interpret complex biomedical and healthcare data in scenarios where
      traditional statistical methods may not be able to perform. In this review
      article, we discuss the basics of machine learning algorithms and what potential
      data sources exist; evaluate the need for machine learning; and examine the
      potential limitations and challenges of implementing machine in the context of
      cardiovascular medicine. The most promising avenues for AI in medicine are the
      development of automated risk prediction algorithms which can be used to guide
      clinical care; use of unsupervised learning techniques to more precisely
      phenotype complex disease; and the implementation of reinforcement learning
      algorithms to intelligently augment healthcare providers. The utility of a
      machine learning-based predictive model will depend on factors including data
      heterogeneity, data depth, data breadth, nature of modelling task, choice of
      machine learning and feature selection algorithms, and orthogonal evidence. A
      critical understanding of the strength and limitations of various methods and
      tasks amenable to machine learning is vital. By leveraging the growing corpus of
      big data in medicine, we detail pathways by which machine learning may facilitate
      optimal development of patient-specific models for improving diagnoses,
      intervention and outcome in cardiovascular medicine.

PMID- 29352007
TI  - Outcomes in anticoagulated patients with atrial fibrillation and with mitral or
      aortic valve disease.
AB  - OBJECTIVE: To assess stroke/systemic embolism, major bleeding and other outcomes,
      and treatment effect of apixaban versus warfarin, in patients with atrial
      fibrillation (AF) and different types of valvular heart disease (VHD), using data
      from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in
      Atrial Fibrillation trial. METHODS: There were 14 793 patients with known VHD
      status, categorised as having moderate or severe mitral regurgitation (MR)
      (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324);
      patients with moderate or severe mitral stenosis were excluded from the trial.
      Baseline characteristics, efficacy and safety outcomes were compared between each
      type and no significant VHD. Treatment effect was assessed using an adjusted
      model. RESULTS: Patients with MR or AR had similar rates of stroke/systemic
      embolism and bleeding compared with patients without MR or AR, respectively.
      Patients with AS had significantly higher event rates (presented as rate per 100
      patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted
      HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI
      1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and
      intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than
      patients without AS. The superiority of apixaban over warfarin on stroke/systemic
      embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to
      1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus
      without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96;
      interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to
      1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the
      primary and secondary efficacy and safety outcomes, there was no evidence of a
      different effect of apixaban over warfarin in patients with any VHD subcategory.
      CONCLUSIONS: In anticoagulated patients with AF, AS is associated with a higher
      risk of stroke/systemic embolism, bleeding and death. The efficacy and safety
      benefits of apixaban compared with warfarin were consistent, regardless of
      presence of MR, AR or AS. CLINICAL TRIAL REGISTRATION: ARISTOTLE clinical trial
      number NCT00412984.

PMID- 29352009
TI  - Cardiovascular health: a global primordial need.

PMID- 29352008
TI  - Incidence, predictors and clinical outcomes of residual stenosis after aortic
      valve-in-valve.
AB  - OBJECTIVE: We aimed to analyse the incidence of prosthesis-patient mismatch (PPM)
      and elevated gradients after aortic valve in valve (ViV), and to evaluate
      predictors and associations with clinical outcomes of this adverse event.
      METHODS: A total of 910 aortic ViV patients were investigated. Elevated residual
      gradients were defined as >=20 mm Hg. PPM was identified based on the indexed
      effective orifice area (EOA), measured by echocardiography, and patient body mass
      index (BMI). Moderate and severe PPM (cases) were defined by European Association
      of Cardiovascular Imaging (EACVI) criteria and compared with patients without PPM
      (controls). RESULTS: Moderate or greater PPM was found in 61% of the patients,
      and severe in 24.6%. Elevated residual gradients were found in 27.9%. Independent
      risk factors for the occurrence of lower indexed EOA and therefore severe PPM
      were higher gradients of the failed bioprosthesis at baseline (unstandardised
      beta -0.023; 95% CI -0.032 to -0.014; P<0.001), a stented (vs a stentless)
      surgical bioprosthesis (unstandardised beta -0.11; 95% CI -0.161 to -0.071;
      P<0.001), higher BMI (unstandardised beta -0.01; 95% CI -0.013 to -0.007;
      P<0.001) and implantation of a SAPIEN/SAPIEN XT/SAPIEN 3 transcatheter device
      (unstandardised beta -0.064; 95% CI -0.095 to -0.032; P<0.001). Neither severe
      PPM nor elevated gradients had an association with VARC II-defined outcomes or 1
      year survival (90.9% severe vs 91.5% moderate vs 89.3% none, P=0.44).
      CONCLUSIONS: Severe PPM and elevated gradients after aortic ViV are very common
      but were not associated with short-term survival and clinical outcomes. The long
      term effect of poor post-ViV haemodynamics on clinical outcomes requires further
      evaluation.

PMID- 29352011
TI  - Persistently high incidence of postcoronary bypass atrial fibrillation: possible
      mechanisms.

PMID- 29352010
TI  - Genetics of syndromic and non-syndromic mitral valve prolapse.
AB  - Mitral valve prolapse (MVP) is a common condition that affects 2%-3% of the
      general population. MVP is thought to include syndromic forms such as Marfan
      syndrome and non-syndromic MVP, which is the most frequent form. Myxomatous
      degeneration and fibroelastic deficiency (FED) are regarded as two different
      forms of non-syndromic MVP. While FED is still considered a degenerative disease
      associated with ageing, frequent familial clustering has been demonstrated for
      myxomatous MVP. Familial and genetic studies led to the recognition of reduced
      penetrance and large phenotypic variability, and to the identification of
      prodromal or atypical forms as a part of the complex spectrum of the disease.
      Whereas autosomal dominant mode is the common inheritance pattern, an X linked
      form of non-syndromic MVP was recognised initially, related to Filamin-A gene,
      encoding for a cytoskeleton protein involved in mechanotransduction. This
      identification allowed a comprehensive description of a new subtype of MVP with a
      unique association of leaflet prolapse and paradoxical restricted motion in
      diastole. In autosomal dominant forms, three loci have been mapped to chromosomes
      16p11-p12, 11p15.4 and 13q31-32. Although deciphering the underlying genetic
      defects is still a work in progress, DCHS1 mutations have been identified
      (11p15.4) in typical myxomatous disease, highlighting new molecular pathways and
      pathophysiological mechanisms leading to the development of MVP. Finally, a large
      international genome-wide association study demonstrated the implication of
      frequent variants in MVP development and opened new directions for future
      research. Hence, this review focuses on phenotypic, genetic and
      pathophysiological aspects of MVP.

PMID- 29352012
TI  - Public transport policy, social engagement and mental health in older age: a
      quasi-experimental evaluation of free bus passes in England.
AB  - BACKGROUND: Social engagement and social isolation are key determinants of mental
      health in older age, yet there is limited evidence on how public policies may
      contribute to reducing isolation, promoting social engagement and improving
      mental health among older people. This study examines the impact of the
      introduction of an age-friendly transportation policy, free bus passes, on the
      mental health of older people in England. METHODS: We use an instrumental
      variable (IV) approach that exploits eligibility criteria for free bus passes to
      estimate the impact of increased public transportation use on depressive
      symptoms, loneliness, social isolation and social engagement. RESULTS:
      Eligibility for the free bus travel pass was associated with an 8% (95% CI 6.4%
      to 9.6%) increase in the use of public transportation among older people. The IV
      model suggests that using public transport reduces depressive symptoms by 0.952
      points (95% CI -1.712 to -0.192) on the Center for Epidemiologic Studies
      Depression Scale. IV models also suggest that using public transport reduces
      feelings of loneliness (beta -0.794, 95% CI -1.528 to -0.061), increases
      volunteering at least monthly (beta 0.237, 95% CI 0.059 to 0.414) and increases
      having regular contact with children (beta 0.480, 95% CI 0.208 to 0.752) and
      friends (beta 0.311, 95% CI 0.109 to 0.513). CONCLUSION: Free bus travel is
      associated with reductions in depressive symptoms and feelings of loneliness
      among older people. Transportation policies may increase older people's social
      engagement and consequently deliver significant benefits to mental health.

PMID- 29352013
TI  - Call for a new epidemiological approach to disaster response.

PMID- 29352014
TI  - Effectiveness of comprehensive social support interventions among elderly
      patients with tuberculosis in communities in China: a community-based trial.
AB  - BACKGROUND: With the increasing of ageing population, tuberculosis in the elderly
      brings a challenge for the tuberculosis (TB) control in China. Enough social
      support can promote the treatment adherence and outcome of the elderly patients
      with TB. Exploring effective interventions to improve the social support of
      patients is of great significance for TB management and control. METHODS: A
      community-based, repeated measurement trial was conducted. Patients with TB >65
      years of age were allocated into the intervention or control group. Patients in
      the intervention group received comprehensive social support interventions, while
      those in the control group received health education alone. The social support
      level of patients was measured at baseline and at the first, third and sixth
      months during the intervention to assess the effectiveness of comprehensive
      social support interventions. RESULTS: A total of 201 patients were recruited
      into the study. Compared with the control group, social support for patients in
      the intervention group increased significantly over time (betagroup*time=0.61,
      P<0.01) in the following three dimensions: objective support
      (betagroup*time=0.15, P<0.05), subjective support (betagroup*time=0.32, P<0.05)
      and support utilisation (betagroup*time=0.16, P<0.05). The change in the scores
      in the control group was not statistically significant. CONCLUSIONS: The
      intervention programme in communities, including health education, psychotherapy
      and family and community support interventions, can improve the social support
      for elderly patients with TB compared with single health education. TRIAL
      REGISTRATION NUMBER: ChiCTR-IOR-16009232.

PMID- 29352016
TI  - Je ne regrette rien?

PMID- 29352015
TI  - Sox2 is required for olfactory pit formation and olfactory neurogenesis through
      BMP restriction and Hes5 upregulation.
AB  - The transcription factor Sox2 is necessary to maintain pluripotency of embryonic
      stem cells, and to regulate neural development. Neurogenesis in the vertebrate
      olfactory epithelium persists from embryonic stages through adulthood. The role
      Sox2 plays for the development of the olfactory epithelium and neurogenesis
      within has, however, not been determined. Here, by analysing Sox2 conditional
      knockout mouse embryos and chick embryos deprived of Sox2 in the olfactory
      epithelium using CRISPR-Cas9, we show that Sox2 activity is crucial for the
      induction of the neural progenitor gene Hes5 and for subsequent differentiation
      of the neuronal lineage. Our results also suggest that Sox2 activity promotes the
      neurogenic domain in the nasal epithelium by restricting Bmp4 expression. The
      Sox2-deficient olfactory epithelium displays diminished cell cycle progression
      and proliferation, a dramatic increase in apoptosis and finally olfactory pit
      atrophy. Moreover, chromatin immunoprecipitation data show that Sox2 directly
      binds to the Hes5 promoter in both the PNS and CNS. Taken together, our results
      indicate that Sox2 is essential to establish, maintain and expand the neuronal
      progenitor pool by suppressing Bmp4 and upregulating Hes5 expression.

PMID- 29352017
TI  - Keeping it real: MRX-Sae2 clipping of natural substrates.
AB  - The yeast Mre11-Rad50-Xrs2 (MRX) complex and Sae2 function together to initiate
      DNA end resection, an essential early step in homology-dependent repair of DNA
      double-strand breaks (DSBs). In this issue of Genes & Development, Wang and
      colleagues (pp. 2331-2336) and Reginato and colleagues (pp. 2325-2330) report
      that a variety of physiological protein blocks, including Ku, RPA, and
      nucleosomes, stimulate MRX-Sae2 endonuclease cleavage in vitro. These studies
      have important implications for how cells deal with a range of barriers to end
      resection and highlight the crucial role of Sae2 in activating MRX cleavage at
      the correct cell cycle stage.

PMID- 29352018
TI  - Oncohistones: drivers of pediatric cancers.
AB  - One of the most striking results in the area of chromatin and cancer in recent
      years has been the identification of recurrent mutations in histone genes in
      pediatric cancers. These mutations occur at high frequency and lead to the
      expression of mutant histones that exhibit oncogenic features. Thus, they are
      termed oncohistones. Thus far, mutations have been found in the genes encoding
      histone H3 and its variants. The expression of the oncohistones affects the
      global chromatin landscape through mechanisms that have just begun to be
      unraveled. In this review, we provide an overview of histone mutations that have
      been identified and discuss the possible mechanisms by which they contribute to
      tumor development. We further discuss the targeted therapies that have been
      proposed to treat cancers expressing oncohistones.

PMID- 29352021
TI  - Proportion of women presenters at medical grand rounds at major academic centres
      in Canada: a retrospective observational study.
AB  - OBJECTIVE: To assess the proportion of women who presented research or medical
      grand rounds at five major academic hospitals in Canada. DESIGN: A cross
      sectional study. SETTING: Five major university-affiliated hospitals in Toronto
      and Calgary. RESULTS: Overall, at all sites and types of academic rounds, there
      were an average of 17% fewer women presenting than men (P<0.001). There were an
      average of 32% and 21% more men presenting at the city-wide grand rounds in
      cities A and B, respectively (P<0.001, P=0.002). There were more male speakers at
      four out of five types of rounds. The proportion of women presenting on average
      was proportional to the Canadian workforce, but on average, below the proportion
      of female residents and medical students (median ratio 1.1, 0.7 and 0.8,
      respectively). CONCLUSION: Our study demonstrated a lower proportion of females
      in an important outlet for academic recognition and role modelling. This provides
      a possible contributing factor to the under-representation of women in academic
      medicine and an area that can be systematically targeted to promote equity.

PMID- 29352022
TI  - Of mice and mental health: facilitating dialogue and seeing further.
AB  - The science of mental life is critical for understanding both how we function,
      and impairments in our functioning. However, understanding the causal mechanisms
      underlying mental health disorders and developing new treatments are challenges
      too great to be solved by any individual approach. There is a growing awareness
      that translational research-from laboratory to patient and back again to animal
      models-will be critical for the improved understanding and treatment of mental
      health disorders. The motivation and intention to pursue translational approaches
      is therefore strong in mental health research, but critically, opportunities for
      interaction between basic scientists and clinicians are relatively limited, and
      vary depending on the institution in which researchers are working. This has
      promoted the development of a 'culture gap' between basic and clinical scientists
      that limits interaction and sharing of knowledge. Here, we provide 14 examples of
      contemporary translational research and call for an increased collaborative
      approach to mental health research that spans clinical diagnoses, levels of
      analysis and bridges between basic to clinical mental health sciences, including,
      but not limited to, psychology and neuroscience. What is needed is an inclusive
      and integrated approach, bringing together scientists working at all levels of
      enquiry with clinicians providing insights on what works (and what does not). To
      stimulate the much-needed innovation in therapeutic techniques, an analysis of
      component parts is critical. Our approach suggests simplifying complex behaviours
      into distinct psychological components. Asking collaboratively driven scientific
      questions about dysfunction will also benefit our fundamental understanding of
      mental life.This article is part of a discussion meeting issue 'Of mice and
      mental health: facilitating dialogue between basic and clinical neuroscientists'.

PMID- 29352019
TI  - Opposing roles of TGFbeta and BMP signaling in prostate cancer development.
AB  - SMAD4 constrains progression of Pten-null prostate cancer and serves as a common
      downstream node of transforming growth factor beta (TGFbeta) and bone
      morphogenetic protein (BMP) pathways. Here, we dissected the roles of TGFbeta
      receptor II (TGFBR2) and BMP receptor II (BMPR2) using a Pten-null prostate
      cancer model. These studies demonstrated that the molecular actions of TGFBR2
      result in both SMAD4-dependent constraint of proliferation and SMAD4-independent
      activation of apoptosis. In contrast, BMPR2 deletion extended survival relative
      to Pten deletion alone, establishing its promoting role in BMP6-driven prostate
      cancer progression. These analyses reveal the complexity of TGFbeta-BMP signaling
      and illuminate potential therapeutic targets for prostate cancer.

PMID- 29352023
TI  - Monoamine abnormalities in the SAPAP3 knockout model of obsessive-compulsive
      disorder-related behaviour.
AB  - Obsessive-compulsive disorder (OCD) is a leading cause of illness-related
      disability, but the neural mechanisms underlying OCD symptoms are unclear. One
      potential mechanism of OCD pathology is monoamine dysregulation. Because of the
      difficulty of studying monoamine signalling in patients, animal models offer a
      viable alternative to understanding this aspect of OCD pathophysiology. We used
      HPLC to characterize post-mortem monoamine levels in lateral orbitofrontal cortex
      (OFC), medial OFC, medial prefrontal cortex and dorsal and ventral striatum of
      SAPAP-3 knockout (KO) mice, a well-validated model of compulsive-like behaviours
      in OCD. As predicted from previous studies, excessive grooming was significantly
      increased in SAPAP-3 KO mice. Overall levels of the serotonin metabolite 5
      hydroxyindoleacetic acid (HIAA) and the ratio of 5HIAA/serotonin (serotonin
      turnover) were increased in all cortical and striatal regions examined. In
      addition, dihydroxyphenylacetic acid/dopamine ratio was increased in lateral OFC,
      and HVA/dopamine ratio was increased in lateral and medial OFC. No baseline
      differences in serotonin or dopamine tissue content were observed. These data
      provide evidence of monoaminergic dysregulation in a translational model of OCD
      symptoms and are consistent with aberrant cortical and striatal serotonin and
      dopamine release/metabolism in SAPAP-3 KO mice. These results are guiding ongoing
      experiments using circuit and cell-type specific manipulations of dopamine and
      serotonin to determine the contributions of these monoaminergic systems to
      compulsive behaviours, and serve here as a touchstone for an expanded discussion
      of these techniques for precise circuit dissection.This article is part of the
      discussion meeting issue 'Of mice and mental health: facilitating dialogue
      between basic and clinical neuroscientists'.

PMID- 29352024
TI  - Neuropharmacology of compulsive eating.
AB  - Compulsive eating behaviour is a transdiagnostic construct observed in certain
      forms of obesity and eating disorders, as well as in the proposed construct of
      'food addiction'. Compulsive eating can be conceptualized as comprising three
      elements: (i) habitual overeating, (ii) overeating to relieve a negative
      emotional state, and (iii) overeating despite adverse consequences.
      Neurobiological processes that include maladaptive habit formation, the emergence
      of a negative affect, and dysfunctions in inhibitory control are thought to drive
      the development and persistence of compulsive eating behaviour. These complex
      psychobehavioural processes are under the control of various neuropharmacological
      systems. Here, we describe the current evidence implicating these systems in
      compulsive eating behaviour, and contextualize them within the three elements. A
      better understanding of the neuropharmacological substrates of compulsive eating
      behaviour has the potential to significantly advance the pharmacotherapy for
      feeding-related pathologies.This article is part of a discussion meeting issue
      'Of mice and mental health: facilitating dialogue between basic and clinical
      neuroscientists'.

PMID- 29352025
TI  - State-of-the-art and future directions for extinction as a translational model
      for fear and anxiety.
AB  - Through advances in both basic and clinical scientific research, Pavlovian fear
      conditioning and extinction have become an exemplary translational model for
      understanding and treating anxiety disorders. Discoveries in associative and
      neurobiological mechanisms underlying extinction have informed techniques for
      optimizing exposure therapy that enhance the formation of inhibitory associations
      and their consolidation and retrieval over time and context. Strategies that
      enhance formation include maximizing prediction-error correction by violating
      expectancies, deepened extinction, occasional reinforced extinction, attentional
      control and removal of safety signals/behaviours. Strategies that enhance
      consolidation include pharmacological agonists of NMDA (i.e. d-cycloserine) and
      mental rehearsal. Strategies that enhance retrieval include multiple contexts,
      retrieval cues, and pharmacological blockade of contextual encoding. Stimulus
      variability and positive affect are posited to influence the formation and the
      retrieval of inhibitory associations. Inhibitory regulation through affect
      labelling is considered a complement to extinction. The translational value of
      extinction will be increased by more investigation of elements central to
      extinction itself, such as extinction generalization, and interactions with other
      learning processes, such as instrumental avoidance reward learning, and with
      other clinically relevant cognitive-emotional processes, such as self-efficacy,
      threat appraisal and emotion regulation, will add translational value. Moreover,
      framing fear extinction and related processes within a developmental context will
      increase their clinical relevance.This article is part of a discussion meeting
      issue 'Of mice and mental health: facilitating dialogue between basic and
      clinical neuroscientists'.

PMID- 29352026
TI  - Addictive behaviour in experimental animals: prospects for translation.
AB  - Since the introduction of intravenous drug self-administration methodology over
      50 years ago, experimental investigation of addictive behaviour has delivered an
      enormous body of data on the neural, psychological and molecular mechanisms of
      drug reward and reinforcement and the neuroadaptations to chronic use. Whether or
      not these behavioural and molecular studies are viewed as modelling the
      underpinnings of addiction in humans, the discussion presented here highlights
      two areas-the impact of drug-associated conditioned stimuli-or drug cues-on drug
      seeking and relapse, and compulsive cocaine seeking. The degree to which these
      findings translate to the clinical state of addiction is considered in terms of
      the underlying neural circuitry and also the ways in which this understanding has
      helped develop new treatments for addiction. The psychological and neural
      mechanisms underlying drug memory reconsolidation and extinction established in
      animal experiments show particular promise in delivering new treatments for
      relapse prevention to the clinic.This article is part of a discussion meeting
      issue 'Of mice and mental health: facilitating dialogue between basic and
      clinical neuroscientists'.

PMID- 29352029
TI  - Dissociable temporal effects of bupropion on behavioural measures of emotional
      and reward processing in depression.
AB  - Antidepressants remediate negative biases in emotional processing early in
      treatment, prior to mood improvement. However, the effects on reward processing
      potentially relevant to the treatment of anhedonia are less clear. Here we
      investigate the early and sustained effects of the dopamine and noradrenaline
      reuptake inhibitor bupropion on behavioural measures of emotional and reward
      processing in currently depressed individuals. Forty-six currently depressed
      patients and 42 healthy controls participated in a repeated measures study,
      during which open-label bupropion was administered to only the patient group over
      a six week period without a placebo group. All participants completed the
      Emotional Test Battery and a probabilistic instrumental learning task at week 0,
      week 2 and week 6. Currently depressed patients displayed negative biases in
      emotional processing and blunted response bias for high-probability wins compared
      to the healthy controls at baseline. Bupropion was found to reduce the negative
      biases in emotional processing early in treatment, including a significant
      decrease in the percentage misclassification of other face emotions as sad and
      the number of negative self-referent words falsely recalled between baseline and
      week 2. Conversely, bupropion was found to initially further reduce the response
      bias for high-probability wins between baseline and week 2. This effect reversed
      with six weeks' bupropion treatment and reward processing was normalized compared
      to the healthy controls. Early in treatment, bupropion acts to reduce negative
      biases in emotional processing but exacerbates impaired reward processing. The
      beneficial actions of bupropion on reward processing then occur later in
      treatment. Such dissociation in the temporal effects of bupropion on emotional
      and reward processing has implications for the treatment of the different symptom
      domains of negative affect and anhedonia in depression.This article is part of a
      discussion meeting issue 'Of mice and mental health: facilitating dialogue
      between basic and clinical neuroscientists'.

PMID- 29352028
TI  - The mysteries of remote memory.
AB  - Long-lasting memories form the basis of our identity as individuals and lie
      central in shaping future behaviours that guide survival. Surprisingly, however,
      our current knowledge of how such memories are stored in the brain and retrieved,
      as well as the dynamics of the circuits involved, remains scarce despite seminal
      technical and experimental breakthroughs in recent years. Traditionally, it has
      been proposed that, over time, information initially learnt in the hippocampus is
      stored in distributed cortical networks. This process-the standard theory of
      memory consolidation-would stabilize the newly encoded information into a lasting
      memory, become independent of the hippocampus, and remain essentially
      unmodifiable throughout the lifetime of the individual. In recent years, several
      pieces of evidence have started to challenge this view and indicate that long
      lasting memories might already ab ovo be encoded, and subsequently stored in
      distributed cortical networks, akin to the multiple trace theory of memory
      consolidation. In this review, we summarize these recent findings and attempt to
      identify the biologically plausible mechanisms based on which a contextual memory
      becomes remote by integrating different levels of analysis: from neural circuits
      to cell ensembles across synaptic remodelling and epigenetic modifications. From
      these studies, remote memory formation and maintenance appear to occur through a
      multi-trace, dynamic and integrative cellular process ranging from the synapse to
      the nucleus, and represent an exciting field of research primed to change quickly
      as new experimental evidence emerges.This article is part of a discussion meeting
      issue 'Of mice and mental health: facilitating dialogue between basic and
      clinical neuroscientists'.

PMID- 29352027
TI  - The thalamus in drug addiction: from rodents to humans.
AB  - Impairments in response inhibition and salience attribution (iRISA) have been
      proposed to underlie the clinical symptoms of drug addiction as mediated by
      cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the
      iRISA model comes from neuroimaging research that has focused on cortical and
      striatal influences with less emphasis on the role of the thalamus. Here, we
      highlight the importance of the thalamus in drug addiction, focusing on animal
      literature findings on thalamic nuclei in the context of drug-seeking, structural
      and functional changes of the thalamus as measured by imaging studies in human
      drug addiction, particularly during drug cue and non-drug reward processing, and
      response inhibition tasks. Findings from the animal literature suggest that the
      paraventricular nucleus of the thalamus, the lateral habenula and the mediodorsal
      nucleus may be involved in the reinstatement, extinction and expression of drug
      seeking behaviours. In support of the iRISA model, the human addiction imaging
      literature demonstrates enhanced thalamus activation when reacting to drug cues
      and reduced thalamus activation during response inhibition. This pattern of
      response was further associated with the severity of, and relapse in, drug
      addiction. Future animal studies could widen their field of focus by
      investigating the specific role(s) of different thalamic nuclei in different
      phases of the addiction cycle. Similarly, future human imaging studies should aim
      to specifically delineate the structure and function of different thalamic
      nuclei, for example, through the application of advanced imaging protocols at
      higher magnetic fields (7 Tesla).This article is part of a discussion meeting
      issue 'Of mice and mental health: facilitating dialogue between basic and
      clinical neuroscientists'.

PMID- 29352030
TI  - The daunting polygenicity of mental illness: making a new map.
AB  - An epochal opportunity to elucidate the pathogenic mechanisms of psychiatric
      disorders has emerged from advances in genomic technology, new computational
      tools and the growth of international consortia committed to data sharing. The
      resulting large-scale, unbiased genetic studies have begun to yield new
      biological insights and with them the hope that a half century of stasis in
      psychiatric therapeutics will come to an end. Yet a sobering picture is coming
      into view; it reveals daunting genetic and phenotypic complexity portending
      enormous challenges for neurobiology. Successful exploitation of results from
      genetics will require eschewal of long-successful reductionist approaches to
      investigation of gene function, a commitment to supplanting much research now
      conducted in model organisms with human biology, and development of new
      experimental systems and computational models to analyse polygenic causal
      influences. In short, psychiatric neuroscience must develop a new scientific map
      to guide investigation through a polygenic terra incognitaThis article is part of
      a discussion meeting issue 'Of mice and mental health: facilitating dialogue
      between basic and clinical neuroscientists'.

PMID- 29352031
TI  - Can we use mice to study schizophrenia?
AB  - The validity of rodent models for the study of psychiatric disorders is
      controversial. Despite great efforts from academic institutions and
      pharmaceutical companies, as of today, no major therapeutic intervention has been
      developed for the treatment of psychiatric disorders based on mechanistic
      insights from rodent models. Here, we argue that despite these historical
      shortcomings, rodent studies are nevertheless instrumental for identifying
      neuronal circuit mechanisms underlying behaviours that are affected in
      psychiatric disorders. Focusing on schizophrenia, we will give four examples of
      rodent models that were generated based on genetic and environmental risk factors
      or pathophysiological evidence as entry points. We will then discuss how circuit
      analysis in these specific examples can be used for testing hypotheses about
      neuronal mechanisms underlying symptoms of schizophrenia, which will then guide
      the development of new therapies.This article is part of a discussion meeting
      issue 'Of mice and mental health: facilitating dialogue between basic and
      clinical neuroscientists'.

PMID- 29352032
TI  - The surprising subtleties of changing fear memory: a challenge for translational
      science.
AB  - Current pharmacological and psychological treatments for disorders of emotional
      memory only dampen the affective response while leaving the original fear memory
      intact. Under adverse circumstances, these original memories regain prominence,
      causing relapses in many patients. The (re)discovery in neuroscience that after
      reactivation consolidated fear memories may return to a transient labile state,
      requiring a process of restabilization in order to persist, offers a window of
      opportunity for modifying fear memories with amnestic agents. This process, known
      as memory reconsolidation, opens avenues for developing a revolutionary treatment
      for emotional memory disorders. The reconsolidation intervention challenges the
      dominant pharmacological and psychological models of treatment: it is only
      effective when the amnestic drug is given in conjunction with memory reactivation
      during a specific time window, and a modification of cognitive processes is a
      boundary condition for changing fear. Notwithstanding the dramatic effects of
      targeting memory reconsolidation in the laboratory (i.e. proof of principle), the
      greatest hurdle to overcome is that the success of the manipulation depends on
      subtle differences in the reactivation procedure. These experimental parameters
      cannot be easily controlled in clinical practice. In harnessing the clinical
      potential of memory reconsolidation, a heuristic for bi-directionally translating
      behavioural neuroscience and clinical science is proposed.This article is part of
      a discussion meeting issue 'Of mice and mental health: facilitating dialogue
      between basic and clinical neuroscientists'.

PMID- 29352033
TI  - Data-driven criteria to assess fear remission and phenotypic variability of
      extinction in rats.
AB  - Fear conditioning is widely employed to examine the mechanisms that underlie
      dysregulations of the fear system. Various manipulations are often used following
      fear acquisition to attenuate fear memories. In rodent studies, freezing is often
      the main output measure to quantify 'fear'. Here, we developed data-driven
      criteria for defining a standard benchmark that indicates remission from
      conditioned fear and for identifying subgroups with differential treatment
      responses. These analyses will enable a better understanding of individual
      differences in treatment responding.This article is part of a discussion meeting
      issue 'Of mice and mental health: facilitating dialogue between basic and
      clinical neuroscientists'.

PMID- 29352034
TI  - Translational new approaches for investigating mood disorders in rodents and what
      they may reveal about the underlying neurobiology of major depressive disorder.
AB  - Mood disorders represent one of society's most costly and challenging health
      burdens. The drug treatments used today were initially discovered serendipitously
      in the 1950s. Animal models were then developed based on the ability of these
      drugs to alter specific behaviours. These models have played a major role in the
      development of the second generation of antidepressants. However, their use has
      been heavily criticized, particularly in relation to whether they recapitulate
      similar underlying biology to the psychiatric disorder they are proposed to
      represent. This article considers our work in the field of affective bias and the
      development of a translational research programme to try to develop and validate
      better animal models. We discuss whether the new data that have arisen from these
      studies support an alternative perspective on the underlying neurobiological
      processes that lead to major depressive disorder (MDD). Specifically, this
      article will consider whether a neuropsychological mechanism involving affective
      biases plays a causal role in the development of MDD and its associated emotional
      and behavioural symptoms. These animal studies also raise the possibility that
      neuropsychological mechanisms involving affective biases are a precursor to,
      rather than a consequence of, the neurotrophic changes linked to MDD.This article
      is part of a discussion meeting issue 'Of mice and mental health: facilitating
      dialogue between basic and clinical neuroscientists'.

PMID- 29352037
TI  - Preface.

PMID- 29352035
TI  - Using mouse transgenic and human stem cell technologies to model genetic
      mutations associated with schizophrenia and autism.
AB  - Solid progress has occurred over the last decade in our understanding of the
      molecular genetic basis of neurodevelopmental disorders, and of schizophrenia and
      autism in particular. Although the genetic architecture of both disorders is far
      more complex than previously imagined, many key loci have at last been
      identified. This has allowed in vivo and in vitro technologies to be refined to
      model specific high-penetrant genetic loci involved in both disorders. Using the
      DISC1/NDE1 and CYFIP1/EIF4E loci as exemplars, we explore the opportunities and
      challenges of using animal models and human-induced pluripotent stem cell
      technologies to further understand/treat and potentially reverse the worst
      consequences of these debilitating disorders.This article is part of a discussion
      meeting issue 'Of mice and mental health: facilitating dialogue between basic and
      clinical neuroscientists'.

PMID- 29352036
TI  - Multiple memory systems, multiple time points: how science can inform treatment
      to control the expression of unwanted emotional memories.
AB  - Memories that have strong emotions associated with them are particularly
      resilient to forgetting. This is not necessarily problematic, however some
      aspects of memory can be. In particular, the involuntary expression of those
      memories, e.g. intrusive memories after trauma, are core to certain psychological
      disorders. Since the beginning of this century, research using animal models
      shows that it is possible to change the underlying memory, for example by
      interfering with its consolidation or reconsolidation. While the idea of
      targeting maladaptive memories is promising for the treatment of stress and
      anxiety disorders, a direct application of the procedures used in non-human
      animals to humans in clinical settings is not straightforward. In translational
      research, more attention needs to be paid to specifying what aspect of memory (i)
      can be modified and (ii) should be modified. This requires a clear
      conceptualization of what aspect of memory is being targeted, and how different
      memory expressions may map onto clinical symptoms. Furthermore, memory processes
      are dynamic, so procedural details concerning timing are crucial when
      implementing a treatment and when assessing its effectiveness. To target
      emotional memory in its full complexity, including its malleability, science
      cannot rely on a single method, species or paradigm. Rather, a constructive
      dialogue is needed between multiple levels of research, all the way 'from mice to
      mental health'.This article is part of a discussion meeting issue 'Of mice and
      mental health: facilitating dialogue between basic and clinical neuroscientists'.

PMID- 29352038
TI  - Microenvironment-induced CD44v6 promotes early disease progression in chronic
      lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) outgrowth depends on signals from the
      microenvironment. We have previously found that in vitro reconstitution of this
      microenvironment induces specific variant isoforms of the adhesion molecule CD44,
      which confer human CLL with high affinity to hyaluronan (HA). Here, we determined
      the in vivo contribution of standard CD44 and its variants to leukemic B-cell
      homing and proliferation in Tcl1 transgenic mice with a B-cell-specific CD44
      deficiency. In these mice, leukemia onset was delayed and leukemic infiltration
      of spleen, liver, and lungs, but not of bone marrow, was decreased. Competitive
      transplantation revealed that CLL homing to spleen and bone marrow required
      functional CD44. Notably, enrichment of CD44v6 variants particularly in spleen
      enhanced CLL engraftment and proliferation, along with increased HA binding. We
      recapitulated CD44v6 induction in the human disease and revealed the involvement
      of MAPK and NF-kappaB signaling upon CD40 ligand and B-cell receptor stimulation
      by in vitro inhibition experiments and chromatin immunoprecipitation assays. The
      investigation of downstream signaling after CD44v6-HA engagement uncovered the
      activation of extracellular signal-regulated kinase and p65. Consequently, anti
      CD44v6 treatment reduced leukemic cell proliferation in vitro in human and mouse,
      confirming the general nature of the findings. In summary, we propose a CD44-NF
      kappaB-CD44v6 circuit in CLL, allowing tumor cells to gain HA binding capacity
      and supporting their proliferation.

PMID- 29352042
TI  - The Enduring Importance and Challenge of Commutability.

PMID- 29352039
TI  - Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium
      falciparum.
AB  - Effective vaccines against malaria caused by Plasmodium falciparum are still
      lacking, and the molecular mechanism of the host-parasite interaction is not
      fully understood. Here we demonstrate that the interaction of RAP2, a parasite
      secreted rhoptry protein that functions in the parasitophorous vacuole formation
      stage of the invasion, and CD147 on the host erythrocyte is essential for
      erythrocyte invasion by P falciparum and is independent from all previously
      identified interactions involved. Importantly, the blockade of the CD147-RAP2
      interaction by HP6H8, a humanized CD147 antibody, completely abolished the
      parasite invasion with both cure and preventative functions in a humanized mouse
      model. Together with its long half-life on human red blood cells and its safety
      profile in cynomolgus monkeys, HP6H8 is the first antibody that offers an
      advantageous approach by targeting a more conserved late-stage parasite ligand
      for preventing as well as treating severe malaria.

PMID- 29352043
TI  - Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA
      from Patients with Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND: Cell-free DNA (cfDNA) is known to provide potential biomarkers for
      predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma
      (PDAC) has not been fully evaluated. The aim of this study was to evaluate the
      clinical applicability of quantitative analysis of multiplex KRAS mutations in
      cell-free DNA from patients with PDAC. METHODS: A total of 106 patients with PDAC
      were enrolled in this prospective study. The concentration and fraction of KRAS
      mutations were determined through multiplex detection of KRAS mutations in plasma
      samples by use of a droplet digital PCR kit (Bio-Rad). RESULTS: KRAS mutations
      were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS
      mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/MUL
      and a median fractional abundance of 0.415%. Multivariable analyses demonstrated
      that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20-3.63]
      and KRAS fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for
      progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05
      3.67) also had prognostic implications for overall survival. Subgroup analyses
      showed that KRAS mutation concentration and fractional abundance significantly
      affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when
      combined with the cancer biomarker CA19-9, the KRAS mutation concentration in
      cfDNA showed additive benefits for the prediction of overall survival.
      CONCLUSIONS: This study demonstrates that multiplex detection of KRAS mutations
      in plasma cfDNA is clinically relevant, providing a potential candidate biomarker
      for prognosis of PDAC.

PMID- 29352044
TI  - Resolution of Spurious Immunonephelometric IgG Subclass Measurement Discrepancies
      by LC-MS/MS.
AB  - BACKGROUND: The Binding Site immunonephelometric (IN) IgG subclass reagents
      (IgG1, IgG2, IgG3, IgG, BSIN) are used for assessment of both immunodeficiency
      and IgG4-related disease (IgG4-RD). In our laboratory, suspected analytic errors
      were noted in patients with increases in IgG4: The sum of the individual IgG
      subclasses was substantially greater than the measured total IgG concentrations
      (unlike samples with normal IgG4), and the IgG4 concentration was always less
      than the IgG2 concentration. METHODS: We developed a tryptic digest LC-MS/MS
      method to quantify IgG1, IgG2, IgG3, and IgG4 in serum. Samples with IgG4
      concentrations ranging from <0.03 g/L to 32 g/L were reanalyzed by LC-MS/MS, and
      a subset was also reanalyzed by Siemens IN (SIN) subclass measurements. RESULTS:
      Multivariate linear regression identified 3 subclass tests with multiple
      predictors of the measured subclass concentration. For these 3 subclasses, the
      predominant predictors were (in terms of LC-MS/MS IgG subclass measurement
      coefficients) BSIN IgG1 = 0.89.IgG1 + 0.4.IgG4; BSIN IgG2 = 0.94.IgG4 +
      0.89.IgG2; and SIN IgG2 = 0.72.IgG2 + 0.24.IgG4. CONCLUSIONS: There is apparent
      IgG4 cross-reactivity with select IN subclass measurements affecting tests from
      both vendors tested. These findings can be explained either by direct cross
      reactivity of the IN reagents with the IgG4 subclass or unique physicochemical
      properties of IgG4 that permit nonspecific binding of IgG4 heavy chain to other
      IgG immunoglobulin heavy chains. Irrespective of the mechanism, the observed
      intermethod discrepancies support the use of LC-MS/MS as the preferred method for
      measurement of IgG subclasses when testing patients with suspected IgG4-RD.

PMID- 29352041
TI  - Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial
      Arrhythmogenesis.
AB  - RATIONALE: Atrial fibrillation (AF) is the most common arrhythmia, and advanced
      age is an inevitable and predominant AF risk factor. However, the mechanisms that
      couple aging and AF propensity remain unclear, making targeted therapeutic
      interventions unattainable. OBJECTIVE: To explore the functional role of an
      important stress response JNK (c-Jun N-terminal kinase) in sarcoplasmic reticulum
      Ca2+ handling and consequently Ca2+-mediated atrial arrhythmias. METHODS AND
      RESULTS: We used a series of cutting-edge electrophysiological and molecular
      techniques, exploited the power of transgenic mouse models to detail the
      molecular mechanism, and verified its clinical applicability in parallel studies
      on donor human hearts. We discovered that significantly increased activity of the
      stress response kinase JNK2 (JNK isoform 2) in the aged atria is involved in
      arrhythmic remodeling. The JNK-driven atrial proarrhythmic mechanism is supported
      by a pathway linking JNK, CaMKII (Ca2+/calmodulin-dependent kinase II), and
      sarcoplasmic reticulum Ca2+ release RyR2 (ryanodine receptor) channels. JNK2
      activates CaMKII, a critical proarrhythmic molecule in cardiac muscle. In turn,
      activated CaMKII upregulates diastolic sarcoplasmic reticulum Ca2+ leak mediated
      by RyR2 channels. This leads to aberrant intracellular Ca2+ waves and enhanced AF
      propensity. In contrast, this mechanism is absent in young atria. In JNK
      challenged animal models, this is eliminated by JNK2 ablation or CaMKII
      inhibition. CONCLUSIONS: We have identified JNK2-driven CaMKII activation as a
      novel mode of kinase crosstalk and a causal factor in atrial arrhythmic
      remodeling, making JNK2 a compelling new therapeutic target for AF prevention and
      treatment.

PMID- 29352045
TI  - Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range
      and Receptive Field Organization of Mouse Retinal Ganglion Cells.
AB  - In the mammalian retina, horizontal cells receive glutamatergic inputs from many
      rod and cone photoreceptors and return feedback signals to them, thereby changing
      photoreceptor glutamate release in a light-dependent manner. Horizontal cells
      also provide feedforward signals to bipolar cells. It is unclear, however, how
      horizontal cell signals also affect the temporal, spatial, and contrast tuning in
      retinal output neurons, the ganglion cells. To study this, we generated a
      genetically modified mouse line in which we eliminated the light dependency of
      feedback by deleting glutamate receptors from mouse horizontal cells. This
      genetic modification allowed us to investigate the impact of horizontal cells on
      ganglion cell signaling independent of the actual mode of feedback in the outer
      retina and without pharmacological manipulation of signal transmission. In
      control and genetically modified mice (both sexes), we recorded the light
      responses of transient OFF-alpha retinal ganglion cells in the intact retina.
      Excitatory postsynaptic currents (EPSCs) were reduced and the cells were tuned to
      lower temporal frequencies and higher contrasts, presumably because photoreceptor
      output was attenuated. Moreover, receptive fields of recorded cells showed a
      significantly altered surround structure. Our data thus suggest that horizontal
      cells are responsible for adjusting the dynamic range of retinal ganglion cells
      and, together with amacrine cells, contribute to the center/surround organization
      of ganglion cell receptive fields in the mouse.SIGNIFICANCE STATEMENT Horizontal
      cells represent a major neuronal class in the mammalian retina and provide
      lateral feedback and feedforward signals to photoreceptors and bipolar cells,
      respectively. The mode of signal transmission remains controversial and,
      moreover, the contribution of horizontal cells to visual processing is still
      elusive. To address the question of how horizontal cells affect retinal output
      signals, we recorded the light responses of transient OFF-alpha retinal ganglion
      cells in a newly generated mouse line. In this mouse line, horizontal cell
      signals were no longer modulated by light. With light response recordings, we
      show that horizontal cells increase the dynamic range of retinal ganglion cells
      for contrast and temporal changes and contribute to the center/surround
      organization of their receptive fields.

PMID- 29352047
TI  - Patients with Desmoplastic Melanoma May Respond to PD-1 Blockade.
AB  - PD-1 blockade achieved responses in 70% of patients with desmoplastic melanoma in
      a retrospective analysis.

PMID- 29352049
TI  - REV-ERB Agonists Block Autophagy in Cancer Cells.
AB  - Disruption of the circadian clock components reduces cancer cell viability in
      vitro and in vivo.

PMID- 29352048
TI  - Fusion-Negative Rhabdomyosarcoma Can Arise from Endothelial Cells.
AB  - Aberrant myogenic activation in endothelial cells can drive fusion-negative
      rhabdomyosarcoma (FN-RMS).

PMID- 29352046
TI  - Local Corticotropin-Releasing Factor Signaling in the Hypothalamic
      Paraventricular Nucleus.
AB  - Corticotropin-releasing factor (CRF) neurons in the hypothalamic paraventricular
      nucleus (PVN) initiate hypothalamic-pituitary-adrenal axis activity through the
      release of CRF into the portal system as part of a coordinated neuroendocrine,
      autonomic, and behavioral response to stress. The recent discovery of neurons
      expressing CRF receptor type 1 (CRFR1), the primary receptor for CRF, adjacent to
      CRF neurons within the PVN, suggests that CRF also signals within the
      hypothalamus to coordinate aspects of the stress response. Here, we characterize
      the electrophysiological and molecular properties of PVN-CRFR1 neurons and
      interrogate their monosynaptic connectivity using rabies virus-based tracing and
      optogenetic circuit mapping in male and female mice. We provide evidence that CRF
      neurons in the PVN form synapses on neighboring CRFR1 neurons and activate them
      by releasing CRF. CRFR1 neurons receive the majority of monosynaptic input from
      within the hypothalamus, mainly from the PVN itself. Locally, CRFR1 neurons make
      GABAergic synapses on parvocellular and magnocellular cells within the PVN. CRFR1
      neurons resident in the PVN also make long-range glutamatergic synapses in
      autonomic nuclei such as the nucleus of the solitary tract. Selective ablation of
      PVN-CRFR1 neurons in male mice elevates corticosterone release during a stress
      response and slows the decrease in circulating corticosterone levels after the
      cessation of stress. Our experiments provide evidence for a novel intra-PVN
      neural circuit that is activated by local CRF release and coordinates autonomic
      and endocrine function during stress responses.SIGNIFICANCE STATEMENT The
      hypothalamic paraventricular nucleus (PVN) coordinates concomitant changes in
      autonomic and neuroendocrine function to organize the response to stress. This
      manuscript maps intra-PVN circuitry that signals via CRF, delineates CRF receptor
      type 1 neuron synaptic targets both within the PVN and at distal targets, and
      establishes the role of this microcircuit in regulating hypothalamic-pituitary
      adrenal axis activity.

PMID- 29352050
TI  - LXR Agonism Depletes MDSCs to Promote Antitumor Immunity.
AB  - LXR activation reduces immunosuppressive MDSCs to activate antitumor cytotoxic T
      cells.

PMID- 29352051
TI  - Long-Term Cognitive Functioning in Testicular Germ-Cell Tumor Survivors.
AB  - BACKGROUND: Treatment for cancer may lead to development of cognitive
      difficulties in cancer survivors. This study aimed to evaluate long-term
      cognitive functioning (CogF) in germ-cell tumor (GCT) survivors. SUBJECTS,
      MATERIALS, AND METHODS: GCT survivors (n = 155) from the National Cancer
      Institute of Slovakia completed the Functional Assessment of Cancer Therapy
      Cognitive Function at a median of 10 years of follow-up (range: 5-32). The study
      group consisted of survivors receiving a cisplatin-based chemotherapy,
      radiotherapy to the retroperitoneal lymph nodes, or both, whereas the control
      group included survivors treated with orchiectomy only. RESULTS: Of the total
      survivors, 138 received treatment beyond orchiectomy and 17 controls had
      orchiectomy alone. Any treatment resulted in significantly greater cognitive
      difficulties on the overall cognitive function score. Treatment with radiotherapy
      was associated with cognitive declines in overall cognitive functioning and in
      subscales for perceived cognitive impairment and cognitive impairment perceived
      by others (both p < .05). The burden of chemotherapy plus radiotherapy or
      radiotherapy versus controls resulted in the impairment in all cognitive
      functioning domains (all p < .05). Overall long-term cognitive impairment was
      independent of age in the multivariable analysis. CONCLUSION: This prospective
      study shows that GCT survivors suffer from a long-term CogF impairment. These
      results may help guide clinicians' decisions in treatment and follow-up of GCTs.
      IMPLICATIONS FOR PRACTICE: In this study, long-term survivors of germ-cell tumors
      have reported cognitive impairment after curative treatment with radiotherapy and
      chemotherapy compared with controls who had treatment with orchiectomy only.
      These data provide an argument against the use of adjuvant radiotherapy for stage
      I seminoma. Unnecessary overtreatment with chemotherapy and additional
      radiotherapy after chemotherapy should be avoided.

PMID- 29352053
TI  - Two Doctors, One Patient, and a Common Goal.

PMID- 29352054
TI  - Increased blood-brain barrier permeability in contralateral hemisphere predicts
      worse outcome in acute ischemic stroke after reperfusion therapy.
AB  - AIMS: We sought to investigate the risk factors of blood-brain barrier (BBB)
      disruption, and its potential impact on 90-day clinical outcome in acute ischemic
      stroke (AIS) patients after reperfusion therapy. METHODS: Consecutive acute
      anterior circulation AIS patients imaged with computed tomographic perfusion
      (CTP) before reperfusion therapy were included. Tmax >6 s was used for the
      volumetric measurement of the hypoperfusion area. BBB permeability (BBBP) was
      calculated as the average relative permeability-surface area product (rPS) within
      the hypoperfusion region (rPShypo-i) and its contralateral mirror region (rPShypo
      c) on CTP-derived PS color maps. Modified Rankin Scale (mRS) score was obtained
      at 90-day post-stroke. RESULTS: A total of 187 patients were included, among whom
      the median age was 73 (61-80) years and 76 (40.6%) were women. Median baseline
      NIHSS score was 12 (7- 16). Ninety-eight (52.4%) patients had mRS score >2.
      Increased rPShypo-i and rPShypo-c were both independently associated with males
      and large infarct volume. The increased rPShypo-i was also independently
      associated with a history of atrial fibrillation and high NIHSS score.
      Multivariable analysis showed higher rPShypo-c was independently associated with
      higher mRS (OR: 1.064, 95% CI 1.011 to 1.121; P=0.018). CONCLUSION: BBBP in both
      the hypoperfusion region and its contralateral mirror region are associated with
      stroke severity, but only increased BBBP in the contralateral mirror
      hypoperfusion region relates to worse outcome after reperfusion therapy.

PMID- 29352052
TI  - Estrogen Receptor-Positive Breast Cancer: Exploiting Signaling Pathways
      Implicated in Endocrine Resistance.
AB  - : Advancements in molecular profiling and endocrine therapy (ET) have led to more
      focused clinical attention on precision medicine. These advances have expanded
      our understanding of breast cancer (BC) pathogenesis and hold promising
      implications for the future of therapy. The estrogen receptor-alpha is a
      predominant endocrine regulatory protein in the breast and in estrogen-induced
      BC. Successful targeting of proteins and genes within estrogen receptor (ER)
      nuclear and nonnuclear pathways remains a clinical goal. Several classes of
      antiestrogenic agents are available for patients with early, advanced, or
      metastatic BC, including selective ER modulators, aromatase inhibitors, and a
      selective ER degrader. Clinical development is focused upon characterizing the
      efficacy and tolerability of inhibitors that target the phosphatidylinositol 3
      kinase (PI3K)/akt murine thymoma viral oncogene (AKT)/mammalian target of
      rapamycin inhibitor (mTOR) signaling pathway or the cyclin-dependent kinase 4/6
      (CDK4/6) cell cycle pathway in women with hormone receptor-positive, human
      epidermal growth receptor 2-negative BC who have demonstrated disease recurrence
      or progression. De novo and acquired resistance remain a major challenge for
      women with BC receiving antiestrogenic therapy. Therefore, sequential combination
      of targeted ET is preferred in these patients, and the ever-increasing
      understanding of resistance mechanisms may better inform the selection of future
      therapy. This review describes the intricate roles of the PI3K/AKT/mTOR and
      CDK4/6 pathways in intracellular signaling and the use of endocrine and endocrine
      based combination therapy in BC. IMPLICATIONS FOR PRACTICE: The foundational
      strategy for treating hormone receptor-positive, human epidermal growth receptor
      2-negative, advanced breast cancer includes the use of endocrine therapy either
      alone or in combination with targeted agents. The use of combination therapy aims
      to downregulate cell-signaling pathways with the intent of minimizing cellular
      "crosstalk," which can otherwise result in continued tumorigenesis or progression
      through redundant pathways. This review provides the clinician with the molecular
      rationale and clinical evidence for these treatments and refers to evidence-based
      guidelines to inform the decision-making process.

PMID- 29352055
TI  - Concomitant conus medullaris arteriovenous shunts and sacral dural arteriovenous
      fistulas: pathophysiological links related to the venous drainage of the lesions
      in a series of five cases.
AB  - BACKGROUND: Spinal cord arteriovenous shunts (scAVSs) are a group of lesions
      located in the spinal cord itself or in the surrounding structures. The most
      common scAVSs are spinal dural arteriovenous fistulas (sDAVFs), which are
      acquired lesions. The pathogenesis of sDAVFs involves thrombosis and venous
      hypertension as trigger factors. Intradural scAVSs such as spinal cord
      arteriovenous nidus type malformations (AVMs) and pial arteriovenous fistulas are
      less common than sDAVFs and are considered to have a so-called 'congenital'
      origin. The association between different concomitant scAVSs is very rare and the
      association of sDAVFs with intradural scAVSs has been described in only a few
      case reports. METHODS: We describe a case series of five patients presenting with
      a conus medullaris AVS associated with a lower lumbar or sacral DAVF. RESULTS:
      Three of our patients were <30 years old at presentation. In four of these five
      cases the intradural scAVS drained caudally, engorging the epidural plexus in the
      same location as the sDAVF. In only one case, who presented with thrombosis of
      the drainage of the main compartment of a conus medullaris pial AVF, was the
      location of the DAVF opposite to the location of the residual drainage.
      CONCLUSION: We discuss the pathophysiological link between scAVS and sDAVF on the
      basis of the rarity of the DAVF, the uncommon association between scAVS and
      sDAVF, the presence of sDAVF in young patients, and the venous hypertension
      created by the venous drainage towards the sacral area responsible for
      angiogenesis creating the dural shunt.

PMID- 29352056
TI  - Relationship between adverse events and antiplatelet drug resistance in
      neurovascular intervention: a meta-analysis.
AB  - BACKGROUND: This meta-analysis aimed to evaluate the association between
      antiplatelet resistance and the risk of procedure-related complications in
      neurovascular interventions. METHODS: We identified relevant articles by
      searching electronic databases and reviewed the reference lists of selected
      papers. The risk of adverse events between antiplatelet responders and
      hyporesponders during neurointervention was compared in eligible clinical
      studies. Risk ratios (RRs) and 95% CIs were pooled using a random-effects meta
      analysis. RESULTS: Of 2134 potentially relevant studies, our search identified 15
      studies enrolling a total of 2365 patients. Pooled RRs showed thromboembolic
      events (TEE) were more frequent in hyporesponders (RR 2.634, 95% CI 1.465 to
      4.734). However, hemorrhagic complications did not differ between the two groups
      (RR 1.236, 95% CI 0.642 to 2.380). In subgroup analysis, hyporesponders showed a
      higher prevalence of TEE with standard antiplatelet medication, but there was no
      obvious difference in TEE between the two arms when using a modified antiplatelet
      medication (RR 3.645, 95% CI 1.537 to 8.646; and RR 1.877, 95% CI 0.749 to
      4.751). Studies using stent placement for aneurysms showed a higher TEE rate in
      hyporesponders (RR 3.221, 95% CI 1.899 to 5.464). CONCLUSION: Antiplatelet
      resistance was significantly associated with TEE in neurointervention, and this
      adverse event was associated with individually-intensified antiplatelet
      medication as well as the type of neurointerventional procedure. Our findings
      support the use of antiplatelet resistance assays and tailored antiplatelet
      medications in neurovascular stent placement as a management strategy to reduce
      thromboembolic risk.

PMID- 29352058
TI  - To be or not 2b? To see or not 2c? Alas, the clock is ticking on TICI.

PMID- 29352057
TI  - Feasibility, complications, morbidity, and mortality results at 6 months for
      aneurysm treatment with the Flow Re-Direction Endoluminal Device: report of SAFE
      study.
AB  - BACKGROUND AND PURPOSE: Flow diverters are increasingly used for the treatment of
      intracranial aneurysms. Evaluation of the first devices available for clinical
      use showed high efficacy of this treatment although safety results were worse
      compared with coiling or balloon-assisted coiling. The Safety and Efficacy
      Analysis of FRED Embolic Device in Aneurysm Treatment (SAFE) trial is a single
      arm, multicenter, prospective study conducted to precisely analyze the safety and
      efficacy of the FRED and FRED Jr devices. METHODS: Unruptured and recanalized
      aneurysms located in the anterior circulation treated with FRED and FRED Jr were
      prospectively included. Adverse events were independently evaluated by a Clinical
      Event Committee with a vascular neurosurgeon and an interventional
      neuroradiologist. Primary safety outcome measures were morbidity and mortality
      rates at 6 months after treatment. RESULTS: A total of 103 patients/aneurysms
      were included in 13 interventional neuroradiology (INR) centers. Aneurysm
      locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%),
      cavernous ICA in 15 (14.6%), anterior cerebral artery or anterior communicating
      artery in nine (8.7%), and middle cerebral artery in eight (7.8%). Aneurysms were
      small (<10 mm) in 71 patients (68.9%). Treatment was successfully performed in
      98/103 patients (95.1%). Thromboembolic (TE) complications occurred in 5/103
      patients (4.9%), intraoperative rupture in 2/103 patients (1.9%), delayed
      aneurysm rupture in 1/103 patient (1.0%), and delayed hematoma occurred in 1/103
      patient (1.0%). Six-months' mortality and morbidity rates were 1/102 (1.0%) and
      2/102 (2.0%), respectively. CONCLUSIONS: Aneurysm treatment with the FRED device
      is safe with low mortality (1.0%) and morbidity (2.0%). CLINICAL TRIAL
      REGISTRATION: NCT02921698.

PMID- 29352059
TI  - Increased blood pressure variability after endovascular thrombectomy for acute
      stroke is associated with worse clinical outcome.
AB  - BACKGROUND AND PURPOSE: Blood pressure variability has been found to contribute
      to worse outcomes after intravenous tissue plasminogen activator, but the
      association has not been established after intra-arterial therapies. METHODS: We
      retrospectively reviewed patients with an ischemic stroke treated with intra
      arterial therapies from 2005 to 2015. Blood pressure variability was measured as
      standard deviation (SD), coefficient of variation (CV), and successive variation
      (SV). Ordinal logistic regression models were fitted to the outcome of the
      modified Rankin Scale (mRS) with univariable predictors of systolic blood
      pressure variability. Multivariable ordinal logistic regression models were
      fitted to the outcome of mRS with covariates that showed independent predictive
      ability (P<0.1). RESULTS: There were 182 patients of mean age 63.2 years and
      51.7% were female. The median admission National Institutes of Health Stroke
      Scalescore was 16 and 47.3% were treated with intravenous tissue plasminogen
      activator. In a univariable ordinal logistic regression analysis, systolic SD,
      CV, and SV were all significantly associated with a 1-point increase in the
      follow-up mRS (OR 2.30-4.38, all P<0.002). After adjusting for potential
      confounders, systolic SV was the best predictor of a 1-point increase in mRS at
      follow-up (OR 2.63-3.23, all P<0.007). CONCLUSIONS: Increased blood pressure
      variability as measured by the SD, CV, and SV consistently predict worse
      neurologic outcomes as measured by follow-up mRS in patients with ischemic stroke
      treated with intra-arterial therapies. The SV is the strongest and most
      consistent predictor of worse outcomes at all time intervals.

PMID- 29352060
TI  - The 100 most cited articles in the endovascular management of intracranial
      aneurysms.
AB  - INTRODUCTION: Endovascular interventions for intracranial aneurysms have evolved
      substantially over the past several decades. A citation rank list is used to
      measure the scientific and/or clinical impact of an article. Our objective was to
      identify and analyze the characteristics of the 100 most cited articles in the
      field of endovascular therapy for intracranial aneurysms. METHODS: We performed a
      retrospective bibliometric analysis between July and August 2017. Articles were
      searched on the Science Citation Index Expanded database using Web of Science in
      order to identify the most cited articles in the endovascular therapy of
      intracranial aneurysms since 1945. Using selected key terms ('intracranial
      aneurysm', 'aneurysm', 'aneurysmal subarachnoid', 'endovascular', 'coiling',
      'stent-assisted', 'balloon-assisted', 'flow-diversion') yielded a total of 16 314
      articles. The top 100 articles were identified and analyzed to extract relevant
      information, including citation count, authorship, article type, subject matter,
      institution, country of origin, and year of publication. RESULTS: Citations for
      the top 100 articles ranged from 133 to 1832. All articles were cited an average
      of 27 times per year. There were 45 prospective studies, including 7 level-II
      randomized controlled trials. Most articles were published in the 2000s (n=53),
      and the majority constituted level III or level IV evidence. Half of the top 100
      articles arose from the USA. CONCLUSION: This study provides a comprehensive
      overview of the most cited articles in the endovascular management of
      intracranial aneurysms. It recognizes the contributions made by key authors and
      institutions, providing an important framework to an enhanced understanding of
      the evidence behind the endovascular treatment of aneurysms.

PMID- 29352061
TI  - What to do about fibrin rich 'tough clots'? Comparing the Solitaire stent
      retriever with a novel geometric clot extractor in an in vitro stroke model.
AB  - BACKGROUND: Despite advances in revascularization tools for large vessel
      occlusion presenting as acute ischemic stroke, a significant subset of clots
      remain recalcitrant to current strategies. We assessed the effectiveness of a
      novel thrombectomy device that was specifically designed to retrieve resistant
      fibrin rich clots, the geometric clot extractor (GCE; Neuravi, Galway, Ireland),
      in an in vitro cerebrovascular occlusion stroke model. METHODS: After introducing
      fibrin rich clot analogues into the middle cerebral artery of the model, we
      compared the rates of recanalization between GCE and Solitaire flow restoration
      stent retriever (SR; Medtronic, Minneapolis, Minnesota, USA; control group)
      cases. A maximum of three passes of each device was allowed. If the SR failed to
      recanalize the vessel after three passes, one pass of the GCE was allowed (rescue
      cases). RESULTS: In a total of 26 thrombectomy cases (13 GCE, 13 SR), successful
      recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was
      achieved 100% of the time in the GCE cases with an average of 2.13 passes per
      case. This rate was significantly higher compared with the Solitaire
      recanalization rate (7.7%, P<0.0001) with an average of three passes per case.
      After SR failure (in 92% of cases), successful one pass GCE rescue recanalization
      was achieved 66% of the time (P<0.005). CONCLUSION: Application of the GCE in
      this experimental stroke model to retrieve typically recalcitrant fibrin rich
      clots resulted in higher successful recanalization rates than the SR.

PMID- 29352062
TI  - Critical role of angiographic acquisition modality and reconstruction on
      morphometric and haemodynamic analysis of intracranial aneurysms.
AB  - BACKGROUND: Subtracted 3-D rotational angiography (3DRA) and cone-beam computed
      tomography angiography (CBCT-A) are often used in assessing cerebral aneurysm
      shape and haemodynamic profile. We sought to evaluate the effect of imaging
      modality, reconstruction parameters, and kernel selection on patient-derived
      aneurysm morphology and computational fluid dynamic (CFD) analysis to assess its
      potential contribution to inter-study variability. METHODS: Four patients (five
      aneurysms) underwent concurrent 3DRA followed by high-resolution CBCT-A. Six
      models were reconstructed per aneurysm: 3DRA reconstructed with 0.28 and 0.14 mm
      voxel sizes (large and small volume of interest (VOI) respectively), and two
      kernel types (normal/smooth). CBCT-A was reconstructed over small VOI using
      normal/sharp kernel. Maximal dome dimension, neck diameter and dome/neck ratio
      were evaluated in 3D. Wall shear stress (WSS) magnitude was evaluated on the
      entire aneurysm dome and in the 5% dome areas covered by lowest (LWSS) and
      highest (HWSS) WSS. Parameters were evaluated with pairwise t-test analysis.
      RESULTS: Smaller VOI reconstructions resulted in smaller Dmax (P value=0.03) and
      Dmax/neck (P value=0.006) and in larger LWSS (P value=0.03). Use of sharp kernel
      led to narrower neck (P value=0.04) and higher Dmax/neck values (P value=0.02).
      CBCT-A resulted in statistically different aneurysm shape (up to 24% difference)
      and haemodynamics (up to 97% difference) compared with 3DRA. CONCLUSION: The
      choice of catheter 3D angiographic modality and reconstruction kernel has a
      critical impact on derived aneurysm morphological and haemodynamic analysis. The
      resultant variability can confound and obscure underlying differences within
      patient populations and between studies performed at different centres using
      divergent techniques, compromising the accuracy of quantitative aneurysm
      analysis.

PMID- 29352064
TI  - GIF Transcriptional Coregulators Control Root Meristem Homeostasis.
AB  - In the root meristem, the quiescent center (QC) is surrounded by stem cells,
      which in turn generate the different cell types of the root. QC cells rarely
      divide under normal conditions but can replenish damaged stem cells. In the
      proximal meristem, the daughters of stem cells, which are referred to as transit
      amplifying cells, undergo additional rounds of cell division prior to
      differentiation. Here, we describe the functions of GRF-INTERACTING FACTORs
      (GIFs), including ANGUSTIFOLIA3 (AN3), in Arabidopsis thaliana roots. GIFs have
      been shown to interact with GRF transcription factors and SWI/SNF chromatin
      remodeling complexes. We found that combinations of GIF mutants cause the loss of
      QC identity. However, despite their QC impairment, GIF mutants have a
      significantly enlarged root meristem with additional lateral root cap layers. We
      show that the increased expression of PLETHORA1 (PLT1) is at least partially
      responsible for the large root meristems of an3 mutants. Furthermore, we found
      that GIFs are necessary for maintaining the precise expression patterns of key
      developmental regulators and that AN3 complexes bind directly to the promoter
      regions of PLT1 as well as SCARECROW We propose that AN3/GIFs participate in
      different pathways that control QC organization and the size of the meristem.

PMID- 29352063
TI  - Arabidopsis thaliana FANCD2 Promotes Meiotic Crossover Formation.
AB  - Fanconi anemia (FA) is a human autosomal recessive disorder characterized by
      chromosomal instability, developmental pathologies, predisposition to cancer, and
      reduced fertility. So far, 19 genes have been implicated in FA, most of them
      involved in DNA repair. Some are conserved across higher eukaryotes, including
      plants. The Arabidopsis thaliana genome encodes a homolog of the Fanconi anemia
      D2 gene (FANCD2) whose function in DNA repair is not yet fully understood. Here,
      we provide evidence that AtFANCD2 is required for meiotic homologous
      recombination. Meiosis is a specialized cell division that ensures reduction of
      genomic content by half and DNA exchange between homologous chromosomes via
      crossovers (COs) prior to gamete formation. In plants, a mutation in AtFANCD2
      results in a 14% reduction of CO numbers. Genetic analysis demonstrated that
      AtFANCD2 acts in parallel to both MUTS HOMOLOG4 (AtMSH4), known for its role in
      promoting interfering COs and MMS AND UV SENSITIVE81 (AtMUS81), known for its
      role in the formation of noninterfering COs. AtFANCD2 promotes noninterfering COs
      in a MUS81-independent manner and is therefore part of an uncharted meiotic CO
      promoting mechanism, in addition to those described previously.

PMID- 29352066
TI  - The Plant Cell Welcomes Assistant Features Editors.

PMID- 29352065
TI  - A Role for MINIYO and QUATRE-QUART2 in the Assembly of RNA Polymerases II, IV,
      and V in Arabidopsis.
AB  - RNA polymerases IV and V (Pol IV and Pol V) are required for the generation of
      noncoding RNAs in RNA-directed DNA methylation (RdDM). Their subunit compositions
      resemble that of Pol II. The mechanism and accessory factors involved in their
      assembly remain largely unknown. In this study, we identified mutant alleles of
      MINIYO (IYO), QUATRE-QUART2 (QQT2), and NUCLEAR RNA POLYMERASE B11/D11/E11
      (NRPB/D/E11) that cause defects in RdDM in Arabidopsis thaliana We found that Pol
      IV-dependent small interfering RNAs and Pol V-dependent transcripts were greatly
      reduced in the mutants. NRPE1, the largest subunit of Pol V, failed to associate
      with other Pol V subunits in the iyo and qqt2 mutants, suggesting the involvement
      of IYO and QQT2 in Pol V assembly. In addition, we found that IYO and QQT2 were
      mutually dependent for their association with the NRPE3 subassembly prior to the
      assembly of Pol V holoenzyme. Finally, we show that IYO and QQT2 are similarly
      required for the assembly of Pol II and Pol IV. Our findings reveal IYO and QQT2
      as cofactors for the assembly of Pol II, Pol IV, and Pol V and provide
      mechanistic insights into how RNA polymerases are assembled in plants.

PMID- 29352067
TI  - Sandwich-Cultured Hepatocytes for Mechanistic Understanding of Hepatic
      Disposition of Parent Drugs and Metabolites by Transporter-Enzyme Interplay.
AB  - Functional interplay between transporters and drug-metabolizing enzymes is
      currently one of the hottest topics in the field of drug metabolism and
      pharmacokinetics. Uptake transporter-enzyme interplay is important to determine
      intrinsic hepatic clearance based on the extended clearance concept. Enzyme and
      efflux transporter interplay, which includes both sinusoidal (basolateral) and
      canalicular efflux transporters, determines the fate of metabolites formed in the
      liver. As sandwich-cultured hepatocytes (SCHs) maintain metabolic activities and
      form a canalicular network, the whole interplay between uptake and efflux
      transporters and drug-metabolizing enzymes can be investigated simultaneously. In
      this article, we review the utility and applicability of SCHs for mechanistic
      understanding of hepatic disposition of both parent drugs and metabolites. In
      addition, the utility of SCHs for mimicking species-specific disposition of
      parent drugs and metabolites in vivo is described. We also review application of
      SCHs for clinically relevant prediction of drug-drug interactions caused by drugs
      and metabolites. The usefulness of mathematical modeling of hepatic disposition
      of parent drugs and metabolites in SCHs is described to allow a quantitative
      understanding of an event in vitro and to develop a more advanced model to
      predict in vivo disposition.

PMID- 29352068
TI  - Maternal-Fetal Disposition and Metabolism of Retrorsine in Pregnant Rats.
AB  - Pyrrolizidine alkaloids (PAs) are extensively synthesized by plants, are commonly
      present in herbs and foodstuffs, and exhibit hepatotoxicity requiring metabolic
      activation by cytochrome P450 3A to form the electrophilic metabolites-pyrrolic
      esters. PAs also cause embryo toxicity, but the metabolic profiles of PAs in
      fetus and placenta have been far from clear. In this study, we determined the
      basal metabolic activation of retrorsine (RTS) in rat maternal liver, placenta,
      and fetal liver in vitro and examined the fetal toxicity and bioactivation of RTS
      in vivo. Detection of microsomal RTS metabolites in vitro showed that the basal
      metabolic activity of fetal liver and placenta to RTS was much weaker than that
      of maternal liver. In addition, a higher rate of pyrrolic ester formation was
      found in normal male fetal liver compared with that of female pups. In vivo
      exposure to RTS caused fetal growth retardation, as well as placental and fetal
      liver injury. Little difference in serum RTS was observed in dams and fetuses,
      but the content of pyrrole-protein adduction in the fetal liver was much lower
      than that in maternal liver, which was consistent with basal metabolic activity.
      Unexpectedly, compared with basal metabolism in fetal liver, exposure to RTS
      during middle and late pregnancy caused an opposite gender difference in RTS
      metabolism and CYP3A expression in the fetal liver. For the first time, our study
      showed that RTS can permeate the placenta barrier and entering fetal circulation,
      whereas the intrauterine pyrrolic metabolite was generated mainly by fetal liver
      but not transported from the maternal circulation. Induction of CYP3A by RTS was
      gender-dependent in the fetal liver, which was probably responsible for RTS
      induced fetal hepatic injury, especially for female pups.

PMID- 29352069
TI  - Identification of Ketene-Reactive Intermediate of Erlotinib Possibly Responsible
      for Inactivation of P450 Enzymes.
AB  - Erlotinib (ELT), a tyrosine kinase inhibitor, is widely used for the treatment of
      nonsmall cell lung cancer in clinic. Unfortunately, severe drug-induced liver
      injury and other adverse effects occurred during the treatment. Meanwhile, ELT
      has been reported to be a mechanism-based inactivator of cytochrome P450(CYPs)
      3A4 and 3A5. The objectives of this study were to identify ketene intermediate of
      ELT and investigate the association of the acetylenic bioactivation with the
      enzyme inactivation caused by ELT. A ketene intermediate was detected in human
      microsomal incubations of ELT, using 4-bromobenzylamine as a trapping agent. CYPs
      3A4 and 3A5 mainly contributed to the bioactivation of ELT. Microsomal incubation
      study showed that the ketene intermediate covalently modified the enzyme protein
      at lysine residues and destroyed the structure of heme. The vinyl and ethyl
      analogs of ELT showed minor enzyme inhibitory effect (less than 20%), whereas ELT
      inactivated more than 60% of the enzyme. The present study provided a novel
      bioactivation pathway of ELT and facilitated the understanding of the mechanisms
      of ELT-induced mechanism-based enzyme inactivation and liver injury.

PMID- 29352070
TI  - Review of extraocular muscle biopsies and utility of biopsy in extraocular muscle
      enlargement.
AB  - AIMS: To review the distribution of pathology in extraocular muscle (EOM)
      biopsies performed at a tertiary orbital centre, identify clinical and imaging
      features which are associated with benign or malignant diseases and indicate when
      biopsy is necessary for EOM enlargement. METHODS: Retrospective case series
      including 93 patients with EOM enlargement who underwent an EOM biopsy. Clinical,
      radiological and histopathological information was recorded from the medical
      records. Statistical analysis was used to compare variables between patients with
      malignant and benign biopsies. RESULTS: The median age of subjects was 61.1
      years. Forty-eight cases (52%) were benign and 45 (48%) were malignant. Those
      with malignant pathology were significantly older (P<0.0001). Males were more
      likely affected by a benign disease and females by a malignancy (P=0.029). A
      history of malignancy (P<0.0001) and diplopia (P=0.029) were significant factors
      in predicting a malignancy. Pain (P=0.005) and eyelid erythema (P=0.001) were
      more likely in benign conditions. Idiopathic orbital inflammation was the most
      common benign diagnosis and lymphoma the most common malignancy. CONCLUSIONS:
      Biopsy is warranted in those with an atypical presentation of EOM enlargement or
      suspected of having a malignancy. Some features such as age, gender, pain,
      diplopia, history of malignancy and eyelid erythema may help indicate a
      particular diagnosis; however, clinical features and imaging findings are often
      not pathognomonic of each disease.

PMID- 29352071
TI  - Worsening Renal Function in Patients With Acute Heart Failure Undergoing
      Aggressive Diuresis Is Not Associated With Tubular Injury.
AB  - BACKGROUND: Worsening renal function (WRF) in the setting of aggressive diuresis
      for acute heart failure treatment may reflect renal tubular injury or simply
      indicate a hemodynamic or functional change in glomerular filtration. Well
      validated tubular injury biomarkers, N-acetyl-beta-d-glucosaminidase, neutrophil
      gelatinase-associated lipocalin, and kidney injury molecule 1, are now available
      that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal
      Optimization Strategies Evaluation-Acute Heart Failure) provides an experimental
      platform for the study of mechanisms of WRF during aggressive diuresis for acute
      heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic
      therapy in all patients. We sought to determine whether tubular injury biomarkers
      are associated with WRF in the setting of aggressive diuresis and its association
      with prognosis. METHODS: Patients in the multicenter ROSE-AHF trial with baseline
      and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was
      defined as a >=20% decrease in glomerular filtration rate estimated with cystatin
      C. RESULTS: Consistent with protocol-driven aggressive dosing of loop diuretics,
      participants received a median 560 mg IV furosemide equivalents (interquartile
      range, 300-815 mg), which induced a urine output of 8425 mL (interquartile range,
      6341-10 528 mL) over the 72-hour intervention period. Levels of N-acetyl-beta-d
      glucosaminidase and kidney injury molecule 1 did not change with aggressive
      diuresis (both P>0.59), whereas levels of neutrophil gelatinase-associated
      lipocalin decreased slightly (-8.7 ng/mg; interquartile range, -169 to 35 ng/mg;
      P<0.001). WRF occurred in 21.2% of the population and was not associated with an
      increase in any marker of renal tubular injury: neutrophil gelatinase-associated
      lipocalin (P=0.21), N-acetyl-beta-d-glucosaminidase (P=0.46), or kidney injury
      molecule 1 (P=0.22). Increases in neutrophil gelatinase-associated lipocalin, N
      acetyl-beta-d-glucosaminidase, and kidney injury molecule 1 were paradoxically
      associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile
      increase; 95% confidence interval, 0.69-0.91; P=0.001). CONCLUSIONS: Kidney
      tubular injury does not appear to have an association with WRF in the context of
      aggressive diuresis of patients with acute heart failure. These findings
      reinforce the notion that the small to moderate deteriorations in renal function
      commonly encountered with aggressive diuresis are dissimilar from traditional
      causes of acute kidney injury.

PMID- 29352072
TI  - Sex and Race Differences in Lifetime Risk of Heart Failure With Preserved
      Ejection Fraction and Heart Failure With Reduced Ejection Fraction.
AB  - BACKGROUND: Lifetime risk of heart failure has been estimated to range from 20%
      to 46% in diverse sex and race groups. However, lifetime risk estimates for the 2
      HF phenotypes, HF with preserved ejection fraction (HFpEF) and HF with reduced
      ejection fraction (HFrEF), are not known. METHODS: Participant-level data from 2
      large prospective cohort studies, the CHS (Cardiovascular Health Study) and MESA
      (Multiethnic Study of Atherosclerosis), were pooled, excluding individuals with
      prevalent HF at baseline. Remaining lifetime risk estimates for HFpEF (EF >=45%)
      and HFrEF (EF <45%) were determined at different index ages with the use of a
      modified Kaplan-Meier method with mortality and the other HF subtype as competing
      risks. RESULTS: We included 12 417 participants >45 years of age (22.2% blacks,
      44.8% men) who were followed up for median duration of 11.6 years with 2178
      overall incident HF events with 561 HFrEF events and 726 HFpEF events. At the
      index age of 45 years, the lifetime risk for any HF through 90 years of age was
      higher in men than women (27.4% versus 23.8%). Among HF subtypes, the lifetime
      risk for HFrEF was higher in men than women (10.6% versus 5.8%). In contrast, the
      lifetime risk for HFpEF was similar in men and women. In race-stratified
      analyses, lifetime risk for overall HF was higher in nonblacks than blacks (25.9%
      versus 22.4%). Among HF subtypes, the lifetime risk for HFpEF was higher in
      nonblacks than blacks (11.2% versus 7.7%), whereas that for HFrEF was similar
      across the 2 groups. Among participants with antecedent myocardial infarction
      before HF diagnosis, the remaining lifetime risks for HFpEF and HFrEF were up to
      2.5-fold and 4-fold higher, respectively, compared with those without antecedent
      myocardial infarction. CONCLUSIONS: Lifetime risks for HFpEF and HFrEF vary by
      sex, race, and history of antecedent myocardial infarction. These insights into
      the distribution of HF risk and its subtypes could inform the development of
      targeted strategies to improve population-level HF prevention and control.

PMID- 29352073
TI  - Right Ventricular Myofilament Functional Differences in Humans With Systemic
      Sclerosis-Associated Versus Idiopathic Pulmonary Arterial Hypertension.
AB  - BACKGROUND: Patients with systemic sclerosis (SSc)-associated pulmonary arterial
      hypertension (PAH) have a far worse prognosis than those with idiopathic PAH
      (IPAH). In the intact heart, SSc-PAH exhibits depressed rest and reserve right
      ventricular (RV) contractility compared with IPAH. We tested whether this
      disparity involves underlying differences in myofilament function. METHODS:
      Cardiac myocytes were isolated from RV septal endomyocardial biopsies from
      patients with SSc-PAH, IPAH, or SSc with exertional dyspnea but no resting PAH
      (SSc-d); control RV septal tissue was obtained from nondiseased donor hearts (6-7
      per group). Isolated myocyte passive length-tension and developed tension-calcium
      relationships were determined and correlated with in vivo RV function and
      reserve. RV septal fibrosis was also examined. RESULTS: Myocyte passive stiffness
      from length-tension relations was similarly increased in IPAH and SSc-PAH
      compared with control, although SSc-PAH biopsies had more interstitial fibrosis.
      More striking disparities were found between active force-calcium relations.
      Compared with controls, maximal calcium-activated force (Fmax) was 28% higher in
      IPAH but 37% lower in SSc-PAH. Fmax in SSc-d was intermediate between control and
      SSc-PAH. The calcium concentration required for half-maximal force (EC50) was
      similar between control, IPAH, and SSc-d but lower in SSc-PAH. This disparity
      disappeared in myocytes incubated with the active catalytic subunit of protein
      kinase A. Myocyte Fmax directly correlated with in vivo RV contractility assessed
      by end-systolic elastance (R2 =0.46, P=0.002) and change in end-systolic
      elastance with exercise (R2 =0.49, P=0.008) and was inversely related with
      exercise-induced chamber dilation (R2 =0.63, P<0.002), which also was a marker of
      depressed contractile reserve. CONCLUSIONS: A primary defect in human SSc-PAH
      resides in depressed sarcomere function, whereas this is enhanced in IPAH. These
      disparities correlate with in vivo RV contractility and contractile reserve and
      are consistent with worse clinical outcomes in SSc-PAH. The existence of
      sarcomere disease before the development of resting PAH in patients with SSc-d
      suggests that earlier identification and intervention may prove useful.

PMID- 29352074
TI  - Aldosterone, SGK1, and ion channels in the kidney.
AB  - Hyperaldosteronism, a common cause of hypertension, is strongly connected to Na+,
      K+, and Mg2+ dysregulation. Owing to its steroidal structure, aldosterone is an
      active transcriptional modifier when bound to the mineralocorticoid receptor (MR)
      in cells expressing the enzyme 11beta-hydroxysteroid dehydrogenase 2, such as
      those comprising the aldosterone-sensitive distal nephron (ASDN). One such up
      regulated protein, the ubiquitous serum and glucocorticoid regulated kinase 1
      (SGK1), has the capacity to modulate the surface expression and function of many
      classes of renal ion channels, including those that transport Na+ (ENaC), K+
      (ROMK/BK), Ca2+ (TRPV4/5/6), Mg2+ (TRPM7/6), and Cl- (ClC-K, CFTR). Here, we
      discuss the mechanisms by which ASDN expressed channels are up-regulated by SGK1,
      while highlighting newly discovered pathways connecting aldosterone to
      nonselective cation channels that are permeable to Mg2+ (TRPM7) or Ca2+ (TRPV4).

PMID- 29352076
TI  - Intestinal dysbiosis and permeability: the yin and yang in alcohol dependence and
      alcoholic liver disease.
AB  - Alcohol dependence and alcoholic liver disease represent a major public health
      problem with substantial morbidity and mortality. By yet incompletely understood
      mechanisms, chronic alcohol abuse is associated with increased intestinal
      permeability and alterations of the gut microbiota composition, allowing
      bacterial components, bacteria, and metabolites to reach the portal and the
      systemic circulation. These gut-derived bacterial products are recognized by
      immune cells circulating in the blood or residing in remote organs such as the
      liver leading to the release of pro-inflammatory cytokines which are considered
      important mediators of the liver-gut-brain communication. Although circulating
      cytokines are likely not the sole factors involved, they can induce liver
      inflammation/damage and reach the central nervous system where they favor
      neuroinflammation which is associated with change in mood, cognition, and
      drinking behavior. In this review, the authors focus on the current evidence
      describing the changes that occur in the intestinal microbiota with chronic
      alcohol consumption in conjunction with intestinal barrier breakdown and
      inflammatory changes sustaining the concept of a gut-liver-brain axis in the
      pathophysiology of alcohol dependence and alcoholic liver disease.

PMID- 29352075
TI  - O-Linked beta-N-acetylglucosamine (O-GlcNAc) modification: a new pathway to
      decode pathogenesis of diabetic retinopathy.
AB  - The incidence of diabetes continues to rise among all ages and ethnic groups
      worldwide. Diabetic retinopathy (DR) is a complication of diabetes that affects
      the retinal neurovasculature causing serious vision problems, including
      blindness. Its pathogenesis and severity is directly linked to the chronic
      exposure to high glucose conditions. No treatments are currently available to
      stop the development and progression of DR. To develop new and effective
      therapeutic approaches, it is critical to better understand how hyperglycemia
      contributes to the pathogenesis of DR at the cellular and molecular levels. We
      propose alterations in O-GlcNAc modification of target proteins during diabetes
      contribute to the development and progression of DR. The O-GlcNAc modification is
      regulated through hexosamine biosynthetic pathway. We showed this pathway is
      differentially activated in various retinal vascular cells under high glucose
      conditions perhaps due to their selective metabolic activity. O-GlcNAc
      modification can alter protein stability, activity, interactions, and
      localization. By targeting the same amino acid residues (serine and threonine) as
      phosphorylation, O-GlcNAc modification can either compete or cooperate with
      phosphorylation. Here we will summarize the effects of hyperglycemia-induced O
      GlcNAc modification on the retinal neurovasculature in a cell-specific manner,
      providing new insight into the role of O-GlcNAc modification in early loss of
      retinal pericytes and the pathogenesis of DR.

PMID- 29352077
TI  - Whole-Genome Sequencing of Suppressor DNA Mixtures Identifies Pathways That
      Compensate for Chromosome Segregation Defects in Schizosaccharomyces pombe.
AB  - Suppressor screening is a powerful method to identify genes that, when mutated,
      rescue the temperature sensitivity of the original mutation. Previously, however,
      identification of suppressor mutations has been technically difficult. Due to the
      small genome size of Schizosaccharomyces pombe, we developed a spontaneous
      suppressor screening technique, followed by a cost-effective sequencing method.
      Genomic DNAs of 10 revertants that survived at the restrictive temperature of the
      original temperature sensitive (ts) mutant were mixed together as one sample
      before constructing a library for sequencing. Responsible suppressor mutations
      were identified bioinformatically based on allele frequency. Then, we isolated a
      large number of spontaneous extragenic suppressors for three ts mutants that
      exhibited defects in chromosome segregation at their restrictive temperature.
      Screening provided new insight into mechanisms of chromosome segregation: loss of
      Ufd2 E4 multi-ubiquitination activity suppresses defects of an AAA ATPase, Cdc48.
      Loss of Wpl1, a releaser of cohesin, compensates for the Eso1 mutation, which may
      destabilize sister chromatid cohesion. The segregation defect of a ts histone H2B
      mutant is rescued if it fails to be deubiquitinated by the SAGA complex, because
      H2B is stabilized by monoubiquitination.

PMID- 29352078
TI  - The Highly Divergent Mitochondrial Genomes Indicate That the Booklouse,
      Liposcelis bostrychophila (Psocoptera: Liposcelididae) Is a Cryptic Species.
AB  - The booklouse, Liposcelis bostrychophila is an important storage pest worldwide.
      The mitochondrial (mt) genome of an asexual strain (Beibei, China) of the L.
      bostrychophila comprises two chromosomes; each chromosome contains approximate
      half of the 37 genes typically found in bilateral animals. The mt genomes of two
      sexual strains of L. bostrychophila, however, comprise five and seven
      chromosomes, respectively; each chromosome contains one to six genes. To
      understand mt genome evolution in L. bostrychophila, and whether L.
      bostrychophila is a cryptic species, we sequenced the mt genomes of six strains
      of asexual L. bostrychophila collected from different locations in China,
      Croatia, and the United States. The mt genomes of all six asexual strains of L.
      bostrychophila have two chromosomes. Phylogenetic analysis of mt genome sequences
      divided nine strains of L. bostrychophila into four groups. Each group has a
      distinct mt genome organization and substantial sequence divergence (48.7-87.4%)
      from other groups. Furthermore, the seven asexual strains of L. bostrychophila,
      including the published Beibei strain, are more closely related to two other
      species of booklice, L. paeta and L. sculptilimacula, than to the sexual strains
      of L. bostrychophila Our results revealed highly divergent mt genomes in the
      booklouse, L. bostrychophila, and indicate that L. bostrychophila is a cryptic
      species.

PMID- 29352079
TI  - Identification and Validation of a New Source of Low Grain Cadmium Accumulation
      in Durum Wheat.
AB  - Cadmium (Cd) is a heavy metal that has no known biological function and is toxic
      for many living organisms. The maximum level of Cd concentration allowed in the
      international market for wheat grain is 0.2 mg kg-1 Because phenotyping for Cd
      uptake is expensive and time consuming, molecular markers associated with genes
      conferring low Cd uptake would expedite selection and lead to the development of
      durum cultivars with reduced Cd concentrations. Here, we identified single
      nucleotide polymorphisms (SNPs) associated with a novel low Cd uptake locus in
      the durum experimental line D041735, which has hexaploid common wheat in its
      pedigree. Genetic analysis revealed a single major QTL for Cd uptake on
      chromosome arm 5BL within a 0.3 cM interval flanked by SNP markers. Analysis of
      the intervening sequence revealed a gene with homology to an aluminum-induced
      protein as a candidate gene. Validation and allelism tests revealed that the low
      Cd uptake gene identified in this study is different from the closely linked Cdu1
      B gene, which also resides on 5BL. This study therefore showed that the durum
      experimental line D041735 contains a novel low Cd uptake gene that was likely
      acquired from hexaploid wheat.

PMID- 29352080
TI  - Functional Analysis of Cancer-Associated DNA Polymerase epsilon Variants in
      Saccharomyces cerevisiae.
AB  - DNA replication fidelity relies on base selectivity of the replicative DNA
      polymerases, exonucleolytic proofreading, and postreplicative DNA mismatch repair
      (MMR). Ultramutated human cancers without MMR defects carry alterations in the
      exonuclease domain of DNA polymerase epsilon (Polepsilon). They have been
      hypothesized to result from defective proofreading. However, modeling of the most
      common variant, Polepsilon-P286R, in yeast produced an unexpectedly strong
      mutator effect that exceeded the effect of proofreading deficiency by two orders
      of magnitude and indicated the involvement of other infidelity factors. The in
      vivo consequences of many additional Polepsilon mutations reported in cancers
      remain poorly understood. Here, we genetically characterized 13 cancer-associated
      Polepsilon variants in the yeast system. Only variants directly altering the DNA
      binding cleft in the exonuclease domain elevated the mutation rate. Among these,
      frequently recurring variants were stronger mutators than rare variants, in
      agreement with the idea that mutator phenotype has a causative role in
      tumorigenesis. In nearly all cases, the mutator effects exceeded those of an
      exonuclease-null allele, suggesting that mechanisms distinct from loss of
      proofreading may drive the genome instability in most ultramutated tumors. All
      mutator alleles were semidominant, supporting the view that heterozygosity for
      the polymerase mutations is sufficient for tumor development. In contrast to the
      DNA binding cleft alterations, peripherally located variants, including a highly
      recurrent V411L, did not significantly elevate mutagenesis. Finally, the analysis
      of Polepsilon variants found in MMR-deficient tumors suggested that the majority
      cause no mutator phenotype alone but some can synergize with MMR deficiency to
      increase the mutation rate.

PMID- 29352082
TI  - Clostridial Strain-Specific Characteristics Associated with Necrotizing
      Enterocolitis.
AB  - We aimed at identifying potential bacterial factors linking clostridia with
      necrotizing enterocolitis (NEC). We compared the phenotypic traits, stress
      responses, cellular cytotoxicity, and inflammatory capabilities of the largest
      collection of Clostridium butyricum and Clostridium neonatale strains isolated
      from fecal samples of NEC preterm neonates (PN) and control PNs. When strain
      characteristics were used as explanatory variables, a statistical discriminant
      analysis allowed the separation of NEC and control strains into separate groups.
      Strains isolated from NEC PN were characterized by a higher viability at 30
      degrees C (P = 0.03) and higher aerotolerance (P = 0.01), suggesting that NEC
      strains may have a competitive and/or survival advantage in the environmental
      gastrointestinal tract conditions of NEC PN. Heat-treated NEC bacteria induced
      higher production of interleukin-8 in Caco-2 cells (P = 0.03), suggesting
      proinflammatory activity. In vitro, bacteria, bacterial components, and fecal
      filtrates showed variable cytotoxic effects affecting the cellular network and/or
      cell viability, without specific association with NEC or control samples.
      Altogether, our data support the existence of a specific clostridial strain
      signature associated with NEC.IMPORTANCE Clostridia are part of the commensal
      microbiota in preterm neonates (PN). However, microbiota analyses by culture and
      metagenomics have linked necrotizing enterocolitis (NEC) and intestinal
      colonization with clostridial species. Nevertheless, little is known about the
      specific characteristics that may be shared by clostridia associated with NEC
      compared to commensal clostridia. Therefore, our goal was to identify specific
      bacterial factors linking clostridial strains with NEC. We report the existence
      of a specific bacterial signature associated with NEC and propose that activation
      of the innate immune response may be a unifying causative mechanism for the
      development of NEC independent of a specific pathogenic organism. The present
      study provides new insights into NEC pathophysiology that are needed for better
      diagnostics and strategies for implementing prevention of the disease.

PMID- 29352081
TI  - Pseudomonas aeruginosa Biofilm Antibiotic Resistance Gene ndvB Expression
      Requires the RpoS Stationary-Phase Sigma Factor.
AB  - Chronic, biofilm-based bacterial infections are exceptionally difficult to
      eradicate due to the high degree of antibiotic recalcitrance exhibited by cells
      in biofilm communities. In the opportunistic pathogen Pseudomonas aeruginosa,
      biofilm recalcitrance is multifactorial and arises in part from the preferential
      expression of resistance genes in biofilms compared to exponential-phase
      planktonic cells. One such mechanism involves ndvB, which we have previously
      shown to be expressed specifically in biofilms. In this study, we investigated
      the regulatory basis of this lifestyle-specific expression by developing an
      unstable green fluorescent protein (GFP) transcriptional reporter to observe the
      expression pattern of ndvB We found that in addition to its expression in
      biofilms, ndvB was upregulated in planktonic cells as they enter stationary
      phase. The transcription of ndvB in both growth phases was shown to be dependent
      on the stationary-phase sigma factor RpoS, and mutation of a putative RpoS
      binding site in the ndvB promoter abolished the activity of the promoter in
      stationary-phase cells. Overall, we have expanded our understanding of the
      temporal expression of ndvB in P. aeruginosa and have uncovered a regulatory
      basis for its growth phase-dependent expression.IMPORTANCE Bacterial biofilms are
      more resistant to antibiotics than free-living planktonic cells, and
      understanding the mechanistic basis of this resistance can inform treatments of
      biofilm-based infections. In addition to chemical and structural barriers that
      can inhibit antibiotic entry, the upregulation of specific genes in biofilms
      contributes to the resistance. We investigated this biofilm-specific gene
      induction by examining expression patterns of ndvB, a gene involved in biofilm
      resistance of the opportunistic pathogen Pseudomonas aeruginosa We characterized
      ndvB expression in planktonic and biofilm growth conditions with an unstable
      green fluorescent protein (GFP) reporter and found that the expression of ndvB in
      biofilms is dependent on the stationary-phase sigma factor RpoS. Overall, our
      results support the physiological similarity between biofilms and stationary
      phase cells and suggest that the induction of some stationary-phase genes in
      biofilms may contribute to their increased antibiotic resistance.

PMID- 29352083
TI  - Polyphosphate-accumulating Bacteria: Potential Contributors to Mineral
      Dissolution in the Oral Cavity.
AB  - Bacteria that accumulate polyphosphate have previously been shown to dynamically
      influence the solubility of phosphatic minerals in marine settings and
      wastewater. Here we show that dental plaque, saliva, and carious lesions, all
      contain abundant polyphosphate-accumulating bacteria. Saturation state modeling
      results, informed by phosphate uptake experiments using the model organism
      Lactobacillus rhamnosus, which is known to inhabit advanced carious-lesions,
      suggest that polyphosphate accumulation can lead to undersaturated conditions
      with respect to hydroxyapatite under some oral cavity conditions. The cell
      densities of polyphosphate-accumulating bacteria we observed in some regions of
      oral biofilms are comparable to those that produce undersaturated conditions
      (i.e., those that thermodynamically favor mineral dissolution) in our phosphate
      uptake experiments with L. rhamnosus These results suggest that the localized
      generation of undersaturated conditions by polyphosphate-accumulating bacteria
      constitutes a new potential mechanism of tooth dissolution that may augment the
      effects of metabolic acid production.IMPORTANCE Dental caries is a serious public
      health issue that can have negative impacts on overall quality of life and oral
      health. The role of oral bacteria in the dissolution of dental enamel and dentin
      that can result in carious lesions, has long been solely ascribed to metabolic
      acid production. Here we show that certain oral bacteria may act as a dynamic
      shunt for phosphate in dental biofilms via the accumulation of a polymer known as
      polyphosphate - potentially mediating phosphate-dependent conditions such as
      caries (dental decay).

PMID- 29352084
TI  - Detection of Human Bocavirus Species 2 and 3 in Bivalve Shellfish in Italy.
AB  - Human bocavirus (HBoV) has been shown to be a common cause of respiratory
      infections and gastroenteritis in children. Recently, HBoVs have been detected in
      sewage and river waters in Italy and worldwide. However, studies on their
      presence in other water environments and in bivalve mollusks are not yet
      available. In this study, 316 bivalve shellfish samples collected in three
      Italian regions over a 6-year period (2012 to 2017) were analyzed by nested PCR
      and sequencing using broad-range primer pairs targeting the capsid proteins VP1
      and VP2 of HBoV. The virus was detected in 27 samples (8.5% of the total
      samples), and a statistically significant difference was found within the three
      regions. A further 13 samples, collected in geographic and temporal proximity to
      positive samples, were included in the study to assess the spread of HBoV in
      shellfish production areas at the time of contamination. Twelve of these
      additional samples were found to be positive for HBoV. All positive samples in
      this study were characterized as HBoV species 2 (17 samples; 8 different
      sequences) or species 3 (22 samples; 4 different sequences). This study reports
      the occurrence of HBoV in bivalve shellfish and shows evidence of considerable
      spatial spread of the virus throughout shellfish production areas. Further
      studies are needed to elucidate both the role of HBoV as an agent of
      gastroenteritis and the risk for foodborne transmission of this virus.IMPORTANCE
      Human bocavirus is recognized as an important cause of acute respiratory tract
      infections and has recently been considered an etiological agent of
      gastroenteritis in the pediatric population. Our findings document that HBoVs are
      detected in bivalve shellfish with a relevant prevalence and suggest that an
      assessment of the risk for foodborne transmission of these viruses should be
      undertaken.

PMID- 29352085
TI  - Expression of Genes Involved in Bacteriocin Production and Self-Resistance in
      Lactobacillus brevis 174A Is Mediated by Two Regulatory Proteins.
AB  - We have previously shown that the lactic acid bacterium Lactobacillus brevis
      174A, isolated from Citrus iyo fruit, produces a bacteriocin designated brevicin
      174A, which is comprised of two antibacterial polypeptides (designated brevicins
      174A-beta and 174A-gamma). We have also found a gene cluster, composed of eight
      open reading frames (ORFs), that contains genes for the biosynthesis of brevicin
      174A, self-resistance to its own bacteriocin, and two transcriptional regulatory
      proteins. Some lactic acid bacterial strains have a system to start the
      production of bacteriocin at an adequate stage of growth. Generally, the system
      consists of a membrane-bound histidine protein kinase (HPK) that senses a
      specific environmental stimulus and a corresponding response regulator (RR) that
      mediates the cellular response. We have previously shown that although the HPK-
      and RR-encoding genes are not found on the brevicin 174A biosynthetic gene
      cluster in the 174A strain, two putative regulatory genes, designated breD and
      breG, are in the gene cluster. In the present study, we demonstrate that the
      expression of brevicin 174A production and self-resistance is positively
      controlled by two transcriptional regulatory proteins, designated BreD and BreG.
      BreD is expressed together with BreE as the self-resistance determinant of L.
      brevis 174A. DNase I footprinting analysis and a promoter assay demonstrated that
      BreD binds to the breED promoter as a positive autoregulator. The present study
      also demonstrates that BreG, carrying a transmembrane domain, binds to the common
      promoter of breB and breC, encoding brevicins 174A-beta and 174A-gamma,
      respectively, for positive regulation.IMPORTANCE The problem of the appearance of
      bacteria that are resistant to practical antibiotics and the increasing demand
      for safe foods have increased interest in replacing conventional antibiotics with
      bacteriocin produced by the lactic acid bacteria. This antibacterial substance
      can inhibit the growth of pathogenic bacteria without side effects on the human
      body. The bacteriocin that is produced by a Citrus iyo-derived Lactobacillus
      brevis strain inhibits the growth of pathogenic bacteria such as Listeria
      monocytogenes, Staphylococcus aureus, and Streptococcus mutans In general, lactic
      acid bacterial strains have a system to start the production of bacteriocin at an
      adequate stage of growth, which is called a quorum-sensing system. The system
      consists of a membrane-bound histidine protein kinase that senses a specific
      environmental stimulus and a corresponding response regulator that mediates the
      cellular response. The present study demonstrates that the expression of the
      genes encoding bacteriocin biosynthesis and the self-resistance determinant is
      positively controlled by two transcriptional regulatory proteins.

PMID- 29352086
TI  - Temporal and Spatial Distribution of the Acetic Acid Bacterium Communities
      throughout the Wooden Casks Used for the Fermentation and Maturation of Lambic
      Beer Underlines Their Functional Role.
AB  - Few data have been published on the occurrence and functional role of acetic acid
      bacteria (AAB) in lambic beer production processes, mainly due to their difficult
      recovery and possibly unknown role. Therefore, a novel aseptic sampling method,
      spanning both the spatial and temporal distributions of the AAB and their
      substrates and metabolites, was combined with a highly selective medium and
      matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) as a high-throughput dereplication method followed by comparative
      gene sequencing for their isolation and identification, respectively. The AAB
      (Acetobacter species more than Gluconobacter species) proliferated during two
      phases of the lambic beer production process, represented by Acetobacter
      orientalis during a few days in the beginning of the fermentation and Acetobacter
      pasteurianus from 7 weeks until 24 months of maturation. Competitive exclusion
      tests combined with comparative genomic analysis of all genomes of strains of
      both species available disclosed possible reasons for this successive dominance.
      The spatial analysis revealed that significantly higher concentrations of acetic
      acid (from ethanol) and acetoin (from lactic acid) were produced at the tops of
      the casks, due to higher AAB counts and a higher metabolic activity of the AAB
      species at the air/liquid interface during the first 6 months of lambic beer
      production. In contrast, no differences in AAB species diversity occurred
      throughout the casks.IMPORTANCE Lambic beer is an acidic beer that is the result
      of a spontaneous fermentation and maturation process. Acidic beers are currently
      attracting attention worldwide. Part of the acidity of these beers is caused by
      acetic acid bacteria (AAB). However, due to their difficult recovery, they were
      never investigated extensively regarding their occurrence, species diversity, and
      functional role in lambic beer production. In the present study, a framework was
      developed for their isolation and identification using a novel aseptic sampling
      method in combination with matrix-assisted laser desorption ionization-time of
      flight mass spectrometry as a high-throughput dereplication technique followed by
      accurate molecular identification. The sampling method applied enabled us to take
      spatial differences into account regarding both enumerations and metabolite
      production. In this way, it was shown that more AAB were present and more acetic
      acid was produced at the air/liquid interface during a major part of the lambic
      beer production process. Also, two different AAB species were encountered,
      namely, Acetobacter orientalis at the beginning and Acetobacter pasteurianus in a
      later stage of the production process. This developed framework could also be
      applied for other fermentation processes.

PMID- 29352087
TI  - Subtype-Specific Selection for Resistance to Fluoroquinolones but Not to
      Tetracyclines Is Evident in Campylobacter jejuni Isolates from Beef Cattle in
      Confined Feeding Operations in Southern Alberta, Canada.
AB  - Campylobacter jejuni was longitudinally isolated from beef cattle housed in four
      confined feeding operations (CFOs) in Southern Alberta, Canada, over 18 months.
      All of the cattle were administered a variety of antimicrobial agents (AMAs)
      nontherapeutically and metaphylactically during their time in the CFOs. In total,
      7,966 C. jejuni isolates were recovered from cattle. More animals were colonized
      by the bacterium after >60 days in the CFO (interim) than were individuals upon
      entry at the CFO (arrival). Subtyping and resistance to seven AMAs were
      determined for 1,832 (23.0%) and 1,648 (20.7%) isolates, respectively. Increases
      in the proportion of isolates resistant to tetracycline were observed at all four
      CFOs between sample times and to ciprofloxacin and nalidixic acid at one or more
      CFOs. The vast majority of isolates resistant to tetracycline carried tetO,
      whereas ciprofloxacin resistance was predominantly attributed to mutations in the
      gyrA gene. Although considerable diversity was observed, a majority of C. jejuni
      isolates belonged to one of five predominant subtype clusters. There was no
      difference in subtype diversity by CFO, but the population structure differed
      between sample times. Selection for resistance to ciprofloxacin and nalidixic
      acid was subtype dependent, whereas selection for resistance to tetracycline was
      not. The findings indicate that a proportion of cattle entering CFOs carry
      resistant C. jejuni subtypes, and the characteristics of beef cattle CFOs
      facilitate transmission/proliferation of diverse subtypes, including those
      resistant to AMAs, which coupled with the densities of CFOs likely contribute to
      the high rates of cattle-associated campylobacteriosis in Southern
      Alberta.IMPORTANCE A small proportion of cattle entering a CFO carry
      Campylobacter jejuni, including subtypes resistant to AMAs. The large numbers of
      cattle arriving from diverse locations at the CFOs and intermingling within the
      CFOs over time, coupled with the high-density housing of animals, the high rates
      of transmission of C. jejuni subtypes among animals, and the extensive use of
      AMAs merge to create an ideal situation where the proliferation of diverse
      antimicrobial-resistant C. jejuni subtypes is facilitated. Considering that
      Southern Alberta reports high rates of campylobacteriosis in the human population
      and that many of these clinical cases are due to C. jejuni subtypes associated
      with cattle, it is likely that the characteristics of beef cattle CFOs favor the
      propagation of clinically relevant C. jejuni subtypes, including those resistant
      to medically important AMAs, which constitute a risk to human health.

PMID- 29352088
TI  - An Archaeal Fluoride-Responsive Riboswitch Provides an Inducible Expression
      System for Hyperthermophiles.
AB  - Robust genetic systems for the hyperthermophilic Thermococcales have facilitated
      the overexpression of native genes, enabled the addition of sequences encoding
      secretion signals, epitope, and affinity tags to coding regions, and aided the
      introduction of sequences encoding new proteins in these fast-growing
      fermentative heterotrophs. However, tightly controlled and easily manipulated
      systems facilitating regulated gene expression are limited for these hosts. Here,
      we describe an alternative method for regulatory control reliant on a cis-encoded
      functional riboswitch in the model archaeon Thermococcus kodakarensis Despite the
      hyperthermophilic growth temperatures, the proposed structure of the riboswitch
      conforms to a fluoride-responsive riboswitch encoded in many bacteria and
      similarly functions to regulate a component-conserved fluoride export pathway.
      Deleting components of the fluoride export pathway generates T. kodakarensis
      strains with increased fluoride sensitivity. The mechanism underlying regulated
      expression suggested that the riboswitch-encoding sequences could be utilized as
      a tunable expression cassette. When appended to a reporter gene, the riboswitch
      mediated control system provides fluoride-dependent tunable regulatory potential,
      offering an alternative system for regulating gene expression. Riboswitch
      regulated expression is thus ubiquitous in extant life and can be exploited to
      generate regulated expression systems for hyperthermophiles.IMPORTANCE Gene
      expression is controlled by a myriad of interconnected mechanisms that interpret
      metabolic states and environmental cues to balance cell physiology. Transcription
      regulation in Archaea is known to employ both typical repressors-operators and
      transcription activators to regulate transcription initiation in addition to the
      regulation afforded by chromatin structure. It was perhaps surprising that the
      presumed ancient mechanism of riboswitch-mediated regulation is found in Bacteria
      and Eukarya, but seemingly absent in Archaea We demonstrate here that a fluoride
      responsive riboswitch functions to regulate a detoxification pathway in the
      hyperthermophilic archaeon Thermococcus kodakarensis The results obtained define
      a universal role for riboswitch-mediated regulation, adumbrate the presence of
      several riboswitch-regulated genes in Thermococcus kodakarensis, demonstrate the
      utility of RNA-based regulation at high temperatures, and provide a novel
      riboswitch-regulated expression system to employ in hyperthermophiles.

PMID- 29352089
TI  - Cryptic Production of trans-3-Hydroxyproline in Echinocandin B Biosynthesis.
AB  - Echinocandins are antifungal nonribosomal hexapeptides produced by fungi. Two of
      the amino acids are hydroxy-l-prolines: trans-4-hydroxy-l-proline and, in most
      echinocandin structures, (trans-2,3)-3-hydroxy-(trans-2,4)-4-methyl-l-proline. In
      the case of echinocandin biosynthesis by Glarea lozoyensis, both amino acids are
      found in pneumocandin A0, while in pneumocandin B0 the latter residue is replaced
      by trans-3-hydroxy-l-proline (3-Hyp). We have recently reported that all three
      amino acids are generated by the 2-oxoglutarate-dependent proline hydroxylase
      GloF. In echinocandin B biosynthesis by Aspergillus species, 3-Hyp derivatives
      have not been reported. Here we describe the heterologous production and kinetic
      characterization of HtyE, the 2-oxoglutarate-dependent proline hydroxylase from
      the echinocandin B biosynthetic cluster in Aspergillus pachycristatus
      Surprisingly, l-proline hydroxylation with HtyE resulted in an even higher
      proportion (~30%) of 3-Hyp than that with GloF. This suggests that the
      selectivity for methylated 3-Hyp in echinocandin B biosynthesis is due solely to
      a substrate-specific adenylation domain of the nonribosomal peptide synthetase.
      Moreover, we observed that one product of HtyE catalysis, 3-hydroxy-4-methyl-l
      proline, is slowly further oxidized at the methyl group, giving 3-hydroxy-4
      hydroxymethyl-l-proline, upon prolonged incubation with HtyE. This dihydroxylated
      amino acid has been reported as a building block of cryptocandin, an echinocandin
      produced by CryptosporiopsisIMPORTANCE Secondary metabolites from bacteria and
      fungi are often produced by sets of biosynthetic enzymes encoded in distinct gene
      clusters. Usually, each enzyme catalyzes one biosynthetic step, but multiple
      reactions are also possible. Pneumocandins A0 and B0 are produced by the fungus
      Glarea lozoyensis They belong to the echinocandin family, a group of nonribosomal
      cyclic lipopeptides that exhibit a strong antifungal activity. Chemical
      derivatives are important drugs for the treatment of systemic fungal infections.
      We have recently shown that in the biosynthesis of pneumocandins A0 and B0, three
      hydroxyproline building blocks are provided by one proline hydroxylase. Here we
      demonstrate that the proline hydroxylase from echinocandin B biosynthesis in
      Aspergillus pachycristatus produces the same hydroxyprolines, with an increased
      proportion of trans-3-hydroxyproline. However, echinocandin B biosynthesis does
      not require trans-3-hydroxyproline; its formation remains cryptic. While one can
      only speculate on the evolutionary background of this unexpected finding, proline
      hydroxylation in G. lozoyensis and A. pachycristatus provides an unusual insight
      into peptide antibiotic biosynthesis-namely, the complex interplay between the
      selectivity of a hydroxylase and the substrate specificity of a nonribosomal
      peptide synthetase.

PMID- 29352090
TI  - Production of Ophthalmic Acid Using Engineered Escherichia coli.
AB  - Ophthalmic acid (OA; l-gamma-glutamyl-l-2-aminobutyryl-glycine) is an analog of
      glutathione (GSH; l-gamma-glutamyl-l-cysteinyl-glycine) in which the cysteine
      moiety is replaced by l-2-aminobutyrate. OA is a useful peptide for the
      pharmaceutical and/or food industries. Herein, we report a method for the
      production of OA using engineered Escherichia coli cells. yggS-deficient E. coli,
      which lacks the highly conserved pyridoxal 5'-phosphate-binding protein YggS and
      naturally accumulates OA, was selected as the starting strain. To increase the
      production of OA, we overexpressed the OA biosynthetic enzymes glutamate-cysteine
      ligase (GshA) and glutathione synthase (GshB), desensitized the product
      inhibition of GshA, and eliminated the OA catabolic enzyme gamma
      glutamyltranspeptidase. The production of OA was further enhanced by the deletion
      of miaA and ridA with the aim of increasing the availability of ATP and
      attenuating the unwanted degradation of amino acids, respectively. The final
      strain developed in this study successfully produced 277 MUmol/liter of OA in 24
      h without the formation of by-products in a minimal synthetic medium containing 1
      mM each glutamate, 2-aminobutyrate, and glycine.IMPORTANCE Ophthalmic acid (OA)
      is a peptide that has the potential for use in the pharmaceutical and/or food
      industries. An efficient method for the production of OA would allow us to expand
      our knowledge about its physiological functions and enable the
      industrial/pharmaceutical application of this compound. We demonstrated the
      production of OA using Escherichia coli cells in which OA biosynthetic enzymes
      and degradation enymes were engineered. We also showed that unique approaches,
      including the use of a DeltayggS mutant as a starting strain, the establishment
      of an S495F mutation in GshA, and the deletion of ridA or miaA, facilitated the
      efficient production of OA in E. coli.

PMID- 29352092
TI  - Incident Heart Failure in Patients With Rheumatoid Arthritis: A Nationwide Cohort
      Study.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease
      associated with a wide range of comorbidities, including cardiovascular disease,
      but its association with heart failure (HF) is not fully clear. We investigated
      the risk of incident HF in a nationwide cohort of patients with RA. METHODS AND
      RESULTS: The study comprised the entire Danish population aged >=18 years
      followed from January 1, 2008 until first hospitalization for HF, emigration,
      December 31, 2012, or death. Information on comorbidity, medication, and
      socioeconomic status was identified by individual-level linkage of administrative
      registers. Patients with a rheumatologist diagnosis of RA between 1978 and 2008
      were included. The primary study outcome was incident HF defined as first
      hospital admission for HF. Incidence rates of HF per 1000 person-years were
      calculated and incidence rate ratios adjusted for age, sex, calendar year,
      comorbidity, medications, socioeconomic status, smoking, and alcohol consumption
      were estimated. A total of 4 305 225 subjects with no history of HF were eligible
      for analysis at the study start. Of these subjects, 24 343 developed RA and 50
      623 were hospitalized for HF. Overall incidence rates of incident HF were 2.43
      and 6.64 for the reference population (n=49 879) and patients with RA (n=744),
      respectively. Correspondingly, the fully adjusted incidence rate ratio for
      incident HF was increased in patients with RA with incidence rate ratio 1.30 (95%
      confidence interval, 1.17-1.45). CONCLUSIONS: In this cohort study, RA was
      associated with an increased hospitalization for HF. These findings add
      significantly to the existing evidence of RA as a clinically relevant risk factor
      for HF.

PMID- 29352091
TI  - Precursors of human CD4+ cytotoxic T lymphocytes identified by single-cell
      transcriptome analysis.
AB  - CD4+ cytotoxic T lymphocytes (CD4-CTLs) have been reported to play a protective
      role in several viral infections. However, little is known in humans about the
      biology of CD4-CTL generation, their functional properties, and heterogeneity,
      especially in relation to other well-described CD4+ memory T cell subsets. We
      performed single-cell RNA sequencing in more than 9000 cells to unravel CD4-CTL
      heterogeneity, transcriptional profile, and clonality in humans. Single-cell
      differential gene expression analysis revealed a spectrum of known transcripts,
      including several linked to cytotoxic and costimulatory function that are
      expressed at higher levels in the TEMRA (effector memory T cells expressing
      CD45RA) subset, which is highly enriched for CD4-CTLs, compared with CD4+ T cells
      in the central memory (TCM) and effector memory (TEM) subsets. Simultaneous T
      cell antigen receptor (TCR) analysis in single cells and bulk subsets revealed
      that CD4-TEMRA cells show marked clonal expansion compared with TCM and TEM cells
      and that most of CD4-TEMRA were dengue virus (DENV)-specific in donors with
      previous DENV infection. The profile of CD4-TEMRA was highly heterogeneous across
      donors, with four distinct clusters identified by the single-cell analysis. We
      identified distinct clusters of CD4-CTL effector and precursor cells in the TEMRA
      subset; the precursor cells shared TCR clonotypes with CD4-CTL effectors and were
      distinguished by high expression of the interleukin-7 receptor. Our
      identification of a CD4-CTL precursor population may allow further investigation
      of how CD4-CTLs arise in humans and, thus, could provide insights into the
      mechanisms that may be used to generate durable and effective CD4-CTL immunity.

PMID- 29352093
TI  - Excessive Daytime Sleepiness Independently Predicts Increased Cardiovascular Risk
      After Myocardial Infarction.
AB  - BACKGROUND: Excessive daytime sleepiness (EDS), a common symptom among patients
      with sleep-disordered breathing, is closely associated with the development of
      cardiovascular diseases, but its long-term prognostic value is not completely
      understood. The aim of this study was to investigate whether EDS would be an
      independent prognostic factor after myocardial infarction. METHODS AND RESULTS:
      We prospectively recruited 112 post-myocardial infarction patients. The Epworth
      Sleepiness Scale was completed before polysomnography, and EDS was defined as a
      score >=11. After exclusion of 8 patients who accepted treatment with continuous
      positive airway pressure, 104 patients were followed up for 48 months. The
      primary composite end point was major adverse cardiac events. Patients with EDS
      had higher rates of major adverse cardiac events (48.4% versus 27.4%, chi2=5.27,
      P=0.022) and reinfarction (29.0% versus 5.5%, chi2=13.51, P=0.0002) compared with
      those without EDS. In the Cox proportional hazards model, patients with EDS had
      2.15 times (95% confidence interval, 1.08-4.18; P=0.030) higher crude risk of
      major adverse cardiac events, with prognostic significance persisting after
      adjusting for age, diabetes mellitus, depression, left ventricular ejection
      fraction, apnea-hypopnea index, and nocturnal nadir oxygen saturation (hazard
      ratio: 2.13, 95% confidence interval, 1.04-4.26, P=0.039). Furthermore, among
      participants with moderate to severe sleep-disordered breathing, the presence of
      EDS was associated with higher risk of major adverse cardiac events than those
      without EDS, after adjusting for age and nadir oxygen saturation (hazard ratio:
      3.17, 95% confidence interval, 1.22-7.76, P=0.019). CONCLUSIONS: EDS may be an
      independent prognostic factor of adverse outcome in post-myocardial infarction
      patients with moderate to severe sleep-disordered breathing. Evaluation of EDS
      may shed new light on risk stratification and identify treatment responders for
      this patient population.

PMID- 29352094
TI  - Auditory brainstem function in microcephaly related to Zika virus infection.
AB  - OBJECTIVE: To study the effect of prenatal Zika virus (ZV) infection on brainstem
      function reflected in brainstem auditory evoked potentials (BAEPs). METHODS: In a
      cross-sectional study in 19 children (12 girls) with microcephaly related to ZV
      infection, aged between 12 and 62 weeks, the brainstem function was examined
      through BAEPs. The latencies of wave peaks I, III, and V of the left and right
      ears (n = 37) were standardized according to normative data, and compared between
      them by 2-tailed t test. The confounding variables (cephalic perimeter at the
      born and chronological age) were correlated with the normalized latencies using
      Pearson test. RESULTS: All patients showed, in general, clear waveforms, with
      latencies within 3 SDs of the normative values. However, statistically increased
      latencies of waves I and III (I > III, p = 0.031) were observed, relative to wave
      V (p < 0.001), the latter being closer to respective normative value. The latency
      of wave I was observed to increase with age (r = 0.45, p = 0.005). The waves, in
      turn, did not depend on cephalic perimeter. CONCLUSIONS: These results are
      consistent with the functional normality of the brainstem structure and its lack
      of correlation with microcephaly, suggesting that the disruption produced by the
      ZV infection does not act in the cell proliferation phase, but mostly in the
      processes of neuronal migration and differentiation in the telencephalon.

PMID- 29352095
TI  - Electrophysiologic testing aids diagnosis and subtyping of myoclonus.
AB  - OBJECTIVE: To determine the contribution of electrophysiologic testing in the
      diagnosis and anatomical classification of myoclonus. METHODS: Participants with
      a clinical diagnosis of myoclonus were prospectively recruited, each undergoing a
      videotaped clinical examination and battery of electrophysiologic tests. The
      diagnosis of myoclonus and its subtype was reviewed after 6 months in the context
      of the electrophysiologic findings and specialist review of the videotaped
      clinical examination. RESULTS: Seventy-two patients with myoclonus were
      recruited. Initial clinical anatomical classification included 25 patients with
      cortical myoclonus, 7 with subcortical myoclonus, 2 with spinal myoclonus, and 15
      with functional myoclonic jerks. In 23 cases, clinical anatomical classification
      was not possible because of the complexity of the movement disorder.
      Electrophysiologic testing was completed in 66, with agreement of myoclonus in 60
      (91%) and its subtype in 28 (47%) cases. Subsequent clinical review by a movement
      disorder specialist agreed with the electrophysiologic findings in 52 of 60; in
      the remaining 8, electrophysiologic testing was inconclusive. CONCLUSIONS:
      Electrophysiologic testing is an important additional tool in the diagnosis and
      anatomical classification of myoclonus, also aiding in decision-making regarding
      therapeutic management. Further development of testing criteria is necessary to
      optimize its use in clinical practice.

PMID- 29352096
TI  - Does cigarette smoking do nothing but harm?

PMID- 29352097
TI  - Defining response profiles after alemtuzumab: Rare paradoxical disease
      exacerbation.

PMID- 29352098
TI  - DNA damage response: Selected review and neurologic implications.

PMID- 29352100
TI  - Education Research: Physician identification and patient satisfaction on an
      academic neurology inpatient service.
AB  - OBJECTIVE: To determine the relationship between neurology inpatient satisfaction
      and (1) number of physicians involved in the patient's care and (2) patients'
      ability to identify their physicians. METHODS: A 10-item questionnaire addressing
      patient satisfaction and identification of physicians on the care team was
      administered to patients admitted to an academic, tertiary care, inpatient
      neurology service from May 1 to October 31, 2012. We hypothesized higher
      satisfaction among patients having fewer physicians on the care team and among
      patients able to identify their physicians. RESULTS: A total of 652 patients were
      enrolled. An average of 3.9 (range 3-8) physicians were involved in each
      patient's care. Patients were able to correctly identify on average 2.4 (60.7%)
      physicians involved in their care. Patients who were very satisfied correctly
      identified a larger percentage of physicians involved in their care (63.8% vs
      50.7%, p < 0.001), were more likely to identify a physician who knew them best
      (94.3% vs 43.6%, p < 0.001) and who was "in charge" of their care (94.1% vs
      57.6%, p < 0.001), and were more likely to have private insurance (82.8% vs
      70.5%, p < 0.001) and fewer physicians involved in their care (3.84 vs 4.06, p =
      0.02). CONCLUSIONS: Neurology inpatients' ability to identify physicians involved
      in their care is associated with patient satisfaction. Strategies to enhance
      patient satisfaction might target improving physician identification, reducing
      actual or perceived disparities in care based on payer status, and reducing
      handoffs or conducting handoffs at the bedside.

PMID- 29352099
TI  - Smoking and Parkinson disease: Evidence for gene-by-smoking interactions.
AB  - OBJECTIVE: To investigate whether cigarette smoking interacts with genes involved
      in individual susceptibility to xenobiotics for the risk of Parkinson disease
      (PD). METHODS: Two French population-based case-control studies (513 patients,
      1,147 controls) were included as a discovery sample to examine gene-smoking
      interactions based on 3,179 single nucleotide polymorphisms (SNPs) in 289 genes
      involved in individual susceptibility to xenobiotics. SNP-by-cigarette smoking
      interactions were tested in the discovery sample through an empirical Bayes (EB)
      approach. Nine SNPs were selected for replication in a population-based case
      control study from California (410 patients, 845 controls) with standard logistic
      regression and the EB approach. For SNPs that replicated, we performed pooled
      analyses including the discovery and replication datasets and computed pooled
      odds ratios and confidence intervals (CIs) using random-effects meta-analysis.
      RESULTS: Nine SNPs interacted with smoking in the discovery dataset and were
      selected for replication. Interactions of smoking with rs4240705 in the RXRA gene
      and rs1900586 in the SLC17A6 gene were replicated. In pooled analyses (logistic
      regression), the interactions between smoking and rs4240705-G and rs1900586-G
      were 1.66 (95% CI 1.28-2.14, p = 1.1 * 10-4, p for heterogeneity = 0.366) and
      1.61 (95% CI 1.17-2.21, p = 0.003, p for heterogeneity = 0.616), respectively.
      For both SNPs, while smoking was significantly less frequent in patients than
      controls in AA homozygotes, this inverse association disappeared in G allele
      carriers. CONCLUSIONS: We identified and replicated suggestive gene-by-smoking
      interactions in PD. The inverse association of smoking with PD was less
      pronounced in carriers of minor alleles of both RXRA-rs4240705 and SLC17A6
      rs1900586. These findings may help identify biological pathways involved in the
      inverse association between smoking and PD.

PMID- 29352101
TI  - Activation of disease during therapy with alemtuzumab in 3 patients with multiple
      sclerosis.
AB  - OBJECTIVE: To report 3 patients with multiple sclerosis showing severe activation
      of disease during immunotherapy with alemtuzumab. METHODS: Retrospective case
      series. RESULTS: Patient 1, a 21-year-old woman, developed severe cognitive
      impairment, sight deterioration, severe gait ataxia, urinary retention, and
      extensive progression of cerebral lesion load, including new lesions that
      exhibited gadolinium ring enhancement and dominance of CD19/20-positive B
      lymphocytes, 6 months after induction of alemtuzumab. Patient 2, a 28-year-old
      man, developed left-sided hemihypesthesia and ~60 new cerebral and spinal lesions
      including lesions with gadolinium ring enhancement 6 months after induction of
      alemtuzumab. Patient 3, a 37-year-old woman, developed ataxia and numbness of the
      left thigh, 16 new gadolinium-positive supratentorial lesions, and partly ring
      enhancing and dominance of CD19/20-positive B lymphocytes 6 months after
      induction of alemtuzumab. CONCLUSION: This is a case series reporting severe
      activation of disease during immunotherapy with alemtuzumab. All patients showed
      onset of symptoms 6 months after induction of alemtuzumab, strikingly similar MRI
      lesion morphology, and unexpected high total B cell count, which may suggest a B
      cell-mediated activation of disease. Whether this is due to different rates of B-
      and T cell repopulation has to be the subject of further research. Moreover,
      further effects on the interactions between the adaptive and innate immunity as
      well as between B and T cell lineages might explain the observed disease
      activation.

PMID- 29352102
TI  - Teenage-onset progressive myoclonic epilepsy due to a familial C9orf72 repeat
      expansion.
AB  - BACKGROUND: The progressive myoclonic epilepsies (PME) are a heterogeneous group
      of disorders in which a specific diagnosis cannot be made in a subset of
      patients, despite exhaustive investigation. C9orf72 repeat expansions are
      emerging as an important causal factor in several adult-onset neurodegenerative
      disorders, in particular frontotemporal lobar degeneration and amyotrophic
      lateral sclerosis. An association with PME has not been reported previously.
      OBJECTIVE: To identify the causative mutation in a Belgian family where the
      proband had genetically unexplained PME. RESULTS: We report a 33-year old woman
      who had epilepsy since the age of 15 and then developed progressive cognitive
      deterioration and multifocal myoclonus at the age of 18. The family history
      suggested autosomal dominant inheritance of psychiatric disorders, epilepsy, and
      dementia. Thorough workup for PME including whole exome sequencing did not reveal
      an underlying cause, but a C9orf72 repeat expansion was found in our patient and
      affected relatives. Brain biopsy confirmed the presence of characteristic p62
      positive neuronal cytoplasmic inclusions. CONCLUSION: C9orf72 mutation analysis
      should be considered in patients with PME and psychiatric disorders or dementia,
      even when the onset is in late childhood or adolescence.

PMID- 29352103
TI  - Dynamic cycling of t-SNARE acylation regulates platelet exocytosis.
AB  - Platelets regulate vascular integrity by secreting a host of molecules that
      promote hemostasis and its sequelae. Given the importance of platelet exocytosis,
      it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and
      syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated
      with platelet membranes and redistributed into cholesterol-dependent lipid rafts
      when platelets are activated. Using metabolic labeling and hydroxylamine (HA)/HCl
      treatment, we showed that both contain thioester-linked acyl groups. Mass
      spectrometry mapping further showed that syntaxin-11 was modified on cysteine
      275, 279, 280, 282, 283, and 285, and SNAP-23 was modified on cysteine 79, 80,
      83, 85, and 87. Interestingly, metabolic labeling studies showed incorporation of
      [3H]palmitate into the t-SNAREs increased although the protein levels were
      unchanged, suggesting that acylation turns over on the two t-SNAREs in resting
      platelets. Exogenously added fatty acids did compete with [3H]palmitate for t
      SNARE labeling. To determine the effects of acylation, we measured aggregation,
      ADP/ATP release, as well as P-selectin exposure in platelets treated with the
      acyltransferase inhibitor cerulenin or the thioesterase inhibitor palmostatin B.
      We found that cerulenin pretreatment inhibited t-SNARE acylation and platelet
      function in a dose- and time-dependent manner whereas palmostatin B had no
      detectable effect. Interestingly, pretreatment with palmostatin B blocked the
      inhibitory effects of cerulenin, suggesting that maintaining the acylation state
      is important for platelet function. Thus, our work shows that t-SNARE acylation
      is actively cycling in platelets and suggests that the enzymes regulating protein
      acylation could be potential targets to control platelet exocytosis in vivo.

PMID- 29352104
TI  - A PH-like domain of the Rab12 guanine nucleotide exchange factor DENND3 binds
      actin and is required for autophagy.
AB  - Rab GTPases are key regulators of membrane trafficking, and many are activated by
      guanine nucleotide exchange factors bearing a differentially expressed in normal
      and neoplastic cells (DENN) domain. By activating the small GTPase Rab12, DENN
      domain-containing protein 3 (DENND3) functions in autophagy. Here, we identified
      a structural domain (which we name PHenn) containing a pleckstrin homology
      subdomain that binds actin and is required for DENND3 function in autophagy. We
      found that a hydrophobic patch on an extended beta-turn of the PHenn domain
      mediates an intramolecular interaction with the DENN domain of DENND3. We also
      show that DENND3 binds actin through a surface of positively charged residues on
      the PHenn domain. Substitutions that blocked either DENN or actin binding
      compromised the role of DENND3 in autophagy. These results provide new
      mechanistic insight into the structural determinants regulating DENND3 in
      autophagy and lay the foundation for future investigations of the DENN protein
      family.

PMID- 29352105
TI  - An ornithine omega-aminotransferase required for growth in the absence of
      exogenous proline in the archaeon Thermococcus kodakarensis.
AB  - Aminotransferases are pyridoxal 5'-phosphate-dependent enzymes that catalyze
      reversible transamination reactions between amino acids and alpha-keto acids, and
      are important for the cellular metabolism of nitrogen. Many bacterial and
      eukaryotic omega-aminotransferases that use l-ornithine (Orn), l-lysine (Lys), or
      gamma-aminobutyrate (GABA) have been identified and characterized, but the
      corresponding enzymes from archaea are unknown. Here, we examined the activity
      and function of TK2101, a gene annotated as a GABA aminotransferase, from the
      hyperthermophilic archaeon Thermococcus kodakarensis We overexpressed the TK2101
      gene in T. kodakarensis and purified and characterized the recombinant protein
      and found that it displays only low levels of GABA aminotransferase activity.
      Instead, we observed a relatively high omega-aminotransferase activity with l-Orn
      and l-Lys as amino donors. The most preferred amino acceptor was 2-oxoglutarate.
      To examine the physiological role of TK2101, we created a TK2101 gene-disruption
      strain (DeltaTK2101), which was auxotrophic for proline. Growth comparison with
      the parent strain KU216 and the biochemical characteristics of the protein
      strongly suggested that TK2101 encodes an Orn aminotransferase involved in the
      biosynthesis of l-Pro. Phylogenetic comparisons of the TK2101 sequence with
      related sequences retrieved from the databases revealed the presence of several
      distinct protein groups, some of which having no experimentally studied member.
      We conclude that TK2101 is part of a novel group of Orn aminotransferases that
      are widely distributed at least in the genus Thermococcus, but perhaps also
      throughout the Archaea.

PMID- 29352106
TI  - Cholesterol binding to a conserved site modulates the conformation, pharmacology,
      and transport kinetics of the human serotonin transporter.
AB  - The serotonin transporter (SERT) is important for reuptake of the
      neurotransmitter serotonin from the synaptic cleft and is also the target of most
      antidepressants. It has previously been shown that cholesterol in the membrane
      bilayer affects the conformation of SERT. Although recent crystal structures have
      identified several potential cholesterol-binding sites, it is unclear whether any
      of these potential cholesterol sites are occupied by cholesterol and functionally
      relevant. In the present study, we focus on the conserved cholesterol site 1
      (CHOL1) located in a hydrophobic groove between TM1a, TM5, and TM7. By molecular
      dynamics simulations, we demonstrate a strong binding of cholesterol to CHOL1 in
      a membrane bilayer environment. In biochemical experiments, we find that
      cholesterol depletion induces a more inward-facing conformation favoring
      substrate analog binding. Consistent with this, we find that mutations in CHOL1
      with a negative impact on cholesterol binding induce a more inward-facing
      conformation, and, vice versa, mutations with a positive impact on cholesterol
      binding induce a more outward-facing conformation. This shift in transporter
      conformation dictated by the ability to bind cholesterol in CHOL1 affects the
      apparent substrate affinity, maximum transport velocity, and turnover rates.
      Taken together, we show that occupation of CHOL1 by cholesterol is of major
      importance in the transporter conformational equilibrium, which in turn dictates
      ligand potency and serotonin transport activity. Based on our findings, we
      propose a mechanistic model that incorporates the role of cholesterol binding to
      CHOL1 in the function of SERT.

PMID- 29352107
TI  - Mycolyltransferase from Mycobacterium tuberculosis in covalent complex with
      tetrahydrolipstatin provides insights into antigen 85 catalysis.
AB  - Mycobacterium tuberculosis antigen 85 (Ag85) enzymes catalyze the transfer of
      mycolic acid (MA) from trehalose monomycolate to produce the mycolyl
      arabinogalactan (mAG) or trehalose dimycolate (TDM). These lipids define the
      protective mycomembrane of mycobacteria. The current model of substrate binding
      within the active sites of Ag85s for the production of TDM is not sterically and
      geometrically feasible; additionally, this model does not account for the
      production of mAG. Furthermore, this model does not address how Ag85s limit the
      hydrolysis of the acyl-enzyme intermediate while catalyzing acyl transfer. To
      inform an updated model, we obtained an Ag85 acyl-enzyme intermediate structure
      that resembles the mycolated form. Here, we present a 1.45-A X-ray crystal
      structure of M. tuberculosis Ag85C covalently modified by tetrahydrolipstatin
      (THL), an esterase inhibitor that suppresses M. tuberculosis growth and mimics
      structural attributes of MAs. The mode of covalent inhibition differs from that
      observed in the reversible inhibition of the human fatty-acid synthase by THL.
      Similarities between the Ag85-THL structure and previously determined Ag85C
      structures suggest that the enzyme undergoes structural changes upon acylation,
      and positioning of the peptidyl arm of THL limits hydrolysis of the acyl-enzyme
      adduct. Molecular dynamics simulations of the modeled mycolated-enzyme form
      corroborate the structural analysis. From these findings, we propose an
      alternative arrangement of substrates that rectifies issues with the previous
      model and suggest a direct role for the beta-hydroxy of MA in the second half
      reaction of Ag85 catalysis. This information affords the visualization of a
      complete mycolyltransferase catalytic cycle.

PMID- 29352108
TI  - DeSUMOylation of MKK7 kinase by the SUMO2/3 protease SENP3 potentiates
      lipopolysaccharide-induced inflammatory signaling in macrophages.
AB  - Protein SUMOylation has been reported to play a role in innate immune response,
      but the enzymes, substrates, and consequences of the specific inflammatory
      signaling events are largely unknown. Reactive oxygen species (ROS) are
      abundantly produced during macrophage activation and required for Toll-like
      receptor 4 (TLR4)-mediated inflammatory signaling. Previously, we demonstrated
      that SENP3 is a redox-sensitive SUMO2/3 protease. To explore any links between
      reversible SUMOylation and ROS-related inflammatory signaling in macrophage
      activation, we generated mice with Senp3 conditional knock-out in myeloid cells.
      In bacterial lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation
      models, we found that SENP3 deficiency markedly compromises the activation of
      TLR4 inflammatory signaling and the production of proinflammatory cytokines in
      macrophages exposed to LPS. Moreover, Senp3 conditional knock-out mice were
      significantly less susceptible to septic shock. Of note, SENP3 deficiency was
      associated with impairment in JNK phosphorylation. We found that MKK7, which
      selectively phosphorylates JNK, is a SENP3 substrate and that SENP3-mediated
      deSUMOylation of MKK7 may favor its binding to JNK. Importantly, ROS-dependent
      SENP3 accumulation and MKK7 deSUMOylation rapidly occurred after LPS stimulation.
      In conclusion, our findings indicate that SENP3 potentiates LPS-induced TLR4
      signaling via deSUMOylation of MKK7 leading to enhancement in JNK phosphorylation
      and the downstream events. Therefore this work provides novel mechanistic
      insights into redox regulation of innate immune responses.

PMID- 29352109
TI  - Role of B and T Lymphocyte Attenuator in Renal Transplant Recipients with Biopsy
      Proven Acute Rejection.
AB  - BACKGROUND Acute rejection is a common predisposing cause of allograft
      dysfunction in kidney transplantation. Recently, the B and T lymphocyte
      attenuator (BTLA)/herpes virus entry mediator (HVEM)/lymphotoxin (LIGHT)/CD160
      pathway was found to be potentially involved in the regulation of T cell
      activation. This could mean that this pathway is involved in graft rejection in
      kidney transplantation; the present study aimed to explore this possibility.
      MATERIAL AND METHODS The expression of BTLA, HVEM, LIGHT and CD160 on peripheral
      CD4+, CD8+ and CD19+ lymphocytes were analyzed by flow cytometry in recipients
      with biopsy-proven acute rejection (BPAR) or stable allograft function, as well
      as in healthy volunteers. Moreover, we performed HE staining and
      immunohistochemical staining to assess the expression of BTLA and HVEM in kidney
      samples from recipients with BPAR and patients who underwent the surgery of
      radical nephrectomy. RESULTS We observed the significantly lower expression of
      BTLA on CD4+ T cells in recipients from the BPAR group than in recipients from
      the stable group. The expression of BTLA on CD8+ T cells among recipients both
      from the BPAR and stable group was statistically increased than that in the
      healthy volunteers. A significant difference in the expression of CD160 in the
      stable group was found when compared with the BPAR group or control group.
      Moreover, there was no significance in the expression of HVEM, LIGHT or CD160 on
      other subtypes of T cells between the 3 groups or in the expression of BTLA on
      CD4+ T cells between the BPAR and control group. CONCLUSIONS The findings
      indicate that the BTLA/HVEM pathway does be involved in pathogenesis of acute
      rejection following kidney transplantation, as well as the induction of
      transplant tolerance. This pathway may therefore be a useful target for therapy
      against acute rejection after kidney transplantation.

PMID- 29352110
TI  - Melatonin inhibits apoptotic cell death induced by Vibrio vulnificus VvhA via
      melatonin receptor 2 coupling with NCF-1.
AB  - Melatonin, an endogenous hormone molecule, has a variety of biological functions,
      but a functional role of melatonin in the infection of Gram-negative bacterium
      Vibrio vulnificus has yet to be described. In this study, we investigated the
      molecular mechanism of melatonin in the apoptosis of human intestinal epithelial
      (HCT116) cells induced by the hemolysin (VvhA) produced by V. vulnificus.
      Melatonin (1 MUM) significantly inhibited apoptosis induced by the recombinant
      protein (r) VvhA, which had been inhibited by the knockdown of MT2. The rVvhA
      recruited caveolin-1, NCF-1, and Rac1 into lipid rafts to facilitate the
      production of ROS responsible for the phosphorylation of PKC and JNK.
      Interestingly, melatonin recruited NCF-1 into non-lipid rafts to prevent ROS
      production via MT2 coupling with Galphaq. Melatonin inhibited the JNK-mediated
      phosphorylation of c-Jun responsible for Bax expression, the release of
      mitochondrial cytochrome c, and caspase-3/-9 activation during its promotion of
      rVvhA-induced apoptotic cell death. In addition, melatonin inhibited JNK-mediated
      phosphorylation of Bcl-2 responsible for the release of Beclin-1 and Atg5
      expression during its promotion of rVvhA-induced autophagic cell death. These
      results demonstrate that melatonin signaling via MT2 triggers recruitment of NCF
      1 into non-lipid rafts to block ROS production and JNK-mediated apoptotic and
      autophagic cell deaths induced by rVvhA in intestinal epithelial cells.

PMID- 29352111
TI  - Hepatic SMARCA4 predicts HCC recurrence and promotes tumour cell proliferation by
      regulating SMAD6 expression.
AB  - Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is
      typically diagnosed at advanced stages. Identification and characterisation of
      genes within amplified and deleted chromosomal loci can provide new insights into
      the pathogenesis of cancer and lead to new approaches for diagnosis and therapy.
      In our previous study, we found a recurrent region of copy number amplification
      at 19p13.2 in hepatocellular carcinoma (HCC). In the present study, we performed
      integrated copy number analysis and expression profiling at this locus and a
      putative cancer gene, SMARCA4/BRG1, was uncovered in this region. BRG1 is a part
      of the large ATP-dependent chromatin remodelling complex SWI/SNF. The function of
      BRG1 in various cancers is unclear, including its role in HCC tumorigenesis.
      Here, we found that BRG1 is upregulated in HCC and that its level significantly
      correlates with cancer progression in HCC patients. Importantly, we also found
      that nuclear expression of BRG1 predicts early recurrence for HCC patients.
      Furthermore, we demonstrated that BRG1 promotes HCC cell proliferation in vitro
      and in vivo. BRG1 was observed not only to facilitate S-phase entry but also to
      attenuate cell apoptosis. Finally, we discovered that one of the mechanisms by
      which BRG1 promotes cell proliferation is the upregulation of SMAD6. These
      findings highlight the important role of BRG1 in the regulation of HCC
      proliferation and provide valuable information for cancer prognosis and
      treatment.

PMID- 29352112
TI  - Direct cell-cell contact between mature osteoblasts and osteoclasts dynamically
      controls their functions in vivo.
AB  - Bone homeostasis is regulated by communication between bone-forming mature
      osteoblasts (mOBs) and bone-resorptive mature osteoclasts (mOCs). However, the
      spatial-temporal relationship and mode of interaction in vivo remain elusive.
      Here we show, by using an intravital imaging technique, that mOB and mOC
      functions are regulated via direct cell-cell contact between these cell types.
      The mOBs and mOCs mainly occupy discrete territories in the steady state,
      although direct cell-cell contact is detected in spatiotemporally limited areas.
      In addition, a pH-sensing fluorescence probe reveals that mOCs secrete protons
      for bone resorption when they are not in contact with mOBs, whereas mOCs
      contacting mOBs are non-resorptive, suggesting that mOBs can inhibit bone
      resorption by direct contact. Intermittent administration of parathyroid hormone
      causes bone anabolic effects, which lead to a mixed distribution of mOBs and
      mOCs, and increase cell-cell contact. This study reveals spatiotemporal
      intercellular interactions between mOBs and mOCs affecting bone homeostasis in
      vivo.

PMID- 29352113
TI  - Polo-like kinase 4 mediates epithelial-mesenchymal transition in neuroblastoma
      via PI3K/Akt signaling pathway.
AB  - Neuroblastoma (NB) is the most common malignant tumor in infancy and most common
      extracranial solid tumor in childhood. With the improvement of diagnosis and
      treatment, the survival rate of patients with low-risk and intermediate-risk NB
      can reach up to 90%. In contrast, for high-risk NBs, the long-term survival rate
      is still <40% because of heterogeneity of this tumor. The pathogenesis of NB is
      still not explicit, therefore it is of great significance to explore the
      mechanism of NB tumorigenesis and discover new therapeutic targets for NB. Polo
      like kinase 4 (PLK4), one of the polo-like kinase family members, is an important
      regulator of centriole replication. The aberrant expression of PLK4 was found in
      several cancers and a recent study has unraveled a novel function of PLK4 as a
      mediator of invasion and metastasis in Hela and U2OS cells. However, the function
      of PLK4 in NB development and progression remains to be elucidated. The study
      showed the expression level of PLK4 in NB tissues was remarkably upregulated and
      high expression of PLK4 was negatively correlated with clinical features and
      survival, which suggested that PLK4 could be a potential tumor-promoting factor
      of NB. Functional studies indicated downregulation of PLK4 suppressed migration
      and invasion and promoted apoptosis in NB cells. Further experiments showed that
      downregulation of PLK4 in NB cells inhibited EMT through the PI3K/Akt signaling
      pathway. Animal experiments demonstrated that the downregulation of PLK4 in SK-N
      BE(2) cells dramatically suppressed tumorigenesis and metastasis. PLK4 may be a
      promising therapeutic target for NB.

PMID- 29352114
TI  - Binding of NUFIP2 to Roquin promotes recognition and regulation of ICOS mRNA.
AB  - The ubiquitously expressed RNA-binding proteins Roquin-1 and Roquin-2 are
      essential for appropriate immune cell function and postnatal survival of mice.
      Roquin proteins repress target mRNAs by recognizing secondary structures in their
      3'-UTRs and by inducing mRNA decay. However, it is unknown if other cellular
      proteins contribute to target control. To identify cofactors of Roquin, we used
      RNA interference to screen ~1500 genes involved in RNA-binding or mRNA
      degradation, and identified NUFIP2 as a cofactor of Roquin-induced mRNA decay.
      NUFIP2 binds directly and with high affinity to Roquin, which stabilizes NUFIP2
      in cells. Post-transcriptional repression of human ICOS by endogenous Roquin
      proteins requires two neighboring non-canonical stem-loops in the ICOS 3'-UTR.
      This unconventional cis-element as well as another tandem loop known to confer
      Roquin-mediated regulation of the Ox40 3'-UTR, are bound cooperatively by Roquin
      and NUFIP2. NUFIP2 therefore emerges as a cofactor that contributes to mRNA
      target recognition by Roquin.

PMID- 29352117
TI  - Suppressing autophagy: a strategy by Escherichia coli O157:H7 for its survival on
      host epithelial cells.

PMID- 29352115
TI  - STIL balancing primary microcephaly and cancer.
AB  - Cell division and differentiation are two fundamental physiological processes
      that need to be tightly balanced to achieve harmonious development of an organ or
      a tissue without jeopardizing its homeostasis. The role played by the centriolar
      protein STIL is highly illustrative of this balance at different stages of life
      as deregulation of the human STIL gene expression has been associated with either
      insufficient brain development (primary microcephaly) or cancer, two conditions
      resulting from perturbations in cell cycle and chromosomal segregation. This
      review describes the recent advances on STIL functions in the control of
      centriole duplication and mitotic spindle integrity, and discusses how
      pathological perturbations of its finely tuned expression result in chromosomal
      instability in both embryonic and postnatal situations, highlighting the concept
      that common key factors are involved in developmental steps and tissue
      homeostasis.

PMID- 29352116
TI  - The Chemical Fluctuation Theorem governing gene expression.
AB  - Gene expression is a complex stochastic process composed of numerous enzymatic
      reactions with rates coupled to hidden cell-state variables. Despite advances in
      single-cell technologies, the lack of a theory accurately describing the gene
      expression process has restricted a robust, quantitative understanding of gene
      expression variability among cells. Here we present the Chemical Fluctuation
      Theorem (CFT), providing an accurate relationship between the environment-coupled
      chemical dynamics of gene expression and gene expression variability. Combined
      with a general, accurate model of environment-coupled transcription processes,
      the CFT provides a unified explanation of mRNA variability for various
      experimental systems. From this analysis, we construct a quantitative model of
      transcription dynamics enabling analytic predictions for the dependence of mRNA
      noise on the mRNA lifetime distribution, confirmed against stochastic simulation.
      This work suggests promising new directions for quantitative investigation into
      cellular control over biological functions by making complex dynamics of
      intracellular reactions accessible to rigorous mathematical deductions.

PMID- 29352118
TI  - PI3K/mTOR inhibition promotes the regression of experimental vascular
      malformations driven by PIK3CA-activating mutations.
AB  - Somatic activating mutations within the PIK3CA gene have been recently detected
      in sporadic lymphatic and venous malformations, and in vascular malformations
      (VM) associated to overgrowth syndromes, such as CLOVES and Klippel-Trenaunay
      syndrome. Although VM are often limited to specific tissue areas and can be well
      treated, in extended or recurrent lesions novel therapeutic approaches are
      needed. We generated a mouse model of VM by local expression of PIK3CA-activating
      mutation in endothelial cells. PIK3CA-driven lesions are characterized by large
      areas of hemorrhage, hyperplastic vessels, infiltrates of inflammatory cells, and
      elevated endothelial cell density. Such vascular lesions are ameliorated by
      administration of dual PI3K/mTOR inhibitor, BEZ235, and mTOR inhibitor,
      Everolimus. Unexpectedly, the expression of PIK3CA-activating mutations in human
      endothelial cells results in both increased proliferation rates and senescence.
      Moreover, active forms of PIK3CA strongly promote the angiogenic sprouting.
      Treatment with PI3K/mTOR inhibitors restores normal endothelial cell
      proliferation rate and reduces the amount of senescent cells, whereas treatment
      with Akt inhibitor is less effective. Our findings reveal that PIK3CA mutations
      have a key role in the pathogenesis of VM and PIK3CA-driven experimental lesions
      can be effectively treated by PI3K/mTOR inhibitors.

PMID- 29352119
TI  - Parturition in baboons (PAPIO SPP.).
AB  - The Old World non-human primates (NHP) - baboons (Papio spp.) share similarities
      with humans regarding fetal and placental development and some pregnancy-related
      complications. Information about the mechanism of birth and complications arising
      during parturition in these species is relatively sparse. In this manuscript, we
      add information from a series of pathological and observational cases to
      highlight insights and selected complications of birth in Papio spp, based on
      video-recording of the delivery process, X-ray, MRI, and ultrasound evaluations
      in pregnant baboons. Additionally, we abstracted pathology records obtained from
      perinatal loss in a large baboon colony during a 17 year period. The presented
      cases provide important information for the management of pregnancy and delivery
      in Papio spp.

PMID- 29352120
TI  - Light induced assembly and self-sorting of silica microparticles.
AB  - To tailor the properties of colloidal materials, precise control over the self
      assembly of their constituents is a prerequisite. Here, we govern the assembly of
      silica particles by functionalization with supramolecular moieties which interact
      with each other via directional and reversible hydrogen bonding. Through a
      generally applicable synthesis protocol, two different types of self
      complementary hydrogen bonding moieties, BTA- and UPy-derivatives, are anchored
      to silica particles. Their self-assembly is initiated by the UV-induced removal
      of a photolabile protecting group, allowing the formation of hydrogen bonds
      between tethered molecules. The light-induced assembly of BTA- and UPy-decorated
      colloids in single-component dispersions and colloidal self-sorting in mixed
      dispersions is studied. Furthermore, we demonstrate that UPy-colloids can
      dissasemble upon addition of traces of a competitive binder (NaPy). This work
      provides further insight into the utility of supramolecular handles to
      orchestrate the assembly of micron-sized colloids via non-oligonucleotide
      hydrogen-bonding units.

PMID- 29352121
TI  - Efficient differentiation of human pluripotent stem cells into skeletal muscle
      cells by combining RNA-based MYOD1-expression and POU5F1-silencing.
AB  - Direct generation of skeletal muscle cells from human pluripotent stem cells
      (hPSCs) would be beneficial for drug testing, drug discovery, and disease
      modelling in vitro. Here we show a rapid and robust method to induce myogenic
      differentiation of hPSCs by introducing mRNA encoding MYOD1 together with siRNA
      mediated knockdown of POU5F1 (also known as OCT4 or OCT3/4). This integration
      free approach generates functional skeletal myotubes with sarcomere-like
      structure and a fusion capacity in several days. The POU5F1 silencing facilitates
      MYOD1 recruitment to the target promoters, which results in the significant
      activation of myogenic genes in hPSCs. Furthermore, deep sequencing transcriptome
      analyses demonstrated that POU5F1-knockdown upregulates the genes associated with
      IGF- and FGF-signaling and extracellular matrix that may also support myogenic
      differentiation. This rapid and direct differentiation method may have potential
      applications in regenerative medicine and disease therapeutics for muscle
      disorders such as muscular dystrophy.

PMID- 29352122
TI  - Comparative transcriptomic and proteomic analysis of Arthrobacter sp. CGMCC 3584
      responding to dissolved oxygen for cAMP production.
AB  - Arthrobacter sp. CGMCC 3584 is able to produce high yields of extracellular
      cyclic adenosine monophosphate (cAMP), which plays a vital role in the field of
      treatment of disease and animal food, during aerobic fermentation. However, the
      molecular basis of cAMP production in Arthrobacter species is rarely explored.
      Here, for the first time, we report the comparative transcriptomic and proteomic
      study of Arthrobacter cells to elucidate the higher productivity of cAMP under
      high oxygen supply. We finally obtained 14.1% and 19.3% of the Arthrobacter
      genome genes which were up-regulated and down-regulated notably, respectively,
      with high oxygen supply, and identified 54 differently expressed proteins. Our
      results revealed that high oxygen supply had two major effects on metabolism:
      inhibition of glycolysis, pyruvate metabolism, nitrogen metabolism, and amino
      acid metabolism (histidine, branched-chain amino acids and glutamate metabolism);
      enhancement of the tricarboxylic acid cycle and purine metabolism. We also found
      that regulation of adenylate cyclase and phosphodiesterase was not significant
      under high oxygen supply, suggesting efficient cAMP export might be important in
      cAMP production. These findings may contribute to further understanding of
      capacities of Arthrobacter species and would be highly useful in genetic
      regulation for desirable production.

PMID- 29352123
TI  - Tumor Tissue Detection using Blood-Oxygen-Level-Dependent Functional MRI based on
      Independent Component Analysis.
AB  - Accurate delineation of gliomas from the surrounding normal brain areas helps
      maximize tumor resection and improves outcome. Blood-oxygen-level-dependent
      (BOLD) functional MRI (fMRI) has been routinely adopted for presurgical mapping
      of the surrounding functional areas. For completely utilizing such imaging data,
      here we show the feasibility of using presurgical fMRI for tumor delineation. In
      particular, we introduce a novel method dedicated to tumor detection based on
      independent component analysis (ICA) of resting-state fMRI (rs-fMRI) with
      automatic tumor component identification. Multi-center rs-fMRI data of 32 glioma
      patients from three centers, plus the additional proof-of-concept data of 28
      patients from the fourth center with non-brain musculoskeletal tumors, are fed
      into individual ICA with different total number of components (TNCs). The best
      fitted tumor-related components derived from the optimized TNCs setting are
      automatically determined based on a new template-matching algorithm. The success
      rates are 100%, 100% and 93.75% for glioma tissue detection for the three
      centers, respectively, and 85.19% for musculoskeletal tumor detection. We propose
      that the high success rate could come from the previously overlooked ability of
      BOLD rs-fMRI in characterizing the abnormal vascularization, vasomotion and
      perfusion caused by tumors. Our findings suggest an additional usage of the rs
      fMRI for comprehensive presurgical assessment.

PMID- 29352124
TI  - HBV infection potentiates resistance to S-phase arrest-inducing chemotherapeutics
      by inhibiting CHK2 pathway in diffuse large B-cell lymphoma.
AB  - A considerable number of diffuse large B-cell lymphoma (DLBCL) patients are
      infected with hepatitis B virus (HBV), which is correlated with their poor
      outcomes. However, the role of HBV infection in DLBCL treatment failure remains
      poorly understood. Here, our data demonstrated that HBV infection was closely
      associated with poorer clinical prognosis independent of its hepatic dysfunction
      in germinal center B-cell type (GCB type) DLBCL patients. Interestingly, we found
      that DLBCL cells expressing hepatitis B virus X protein (HBX) did not exhibit
      enhanced cell growth but did show reduced sensitivity to methotrexate (MTX) and
      cytarabine (Ara-C), which induced S-phase arrest. Mechanism studies showed that
      HBX specifically inhibited the phosphorylation of checkpoint kinase 2 (CHK2, a
      key DNA damage response protein). CHK2 depletion similarly conferred resistance
      to the S-phase arrest-inducing chemotherapeutics, consistent with HBX
      overexpression in DLBCL cells. Moreover, overexpression of wild-type CHK2 rather
      than its unphosphorylated mutant (T68A) significantly restored the reduced
      chemosensitivity in HBX-expressing cells, suggesting that HBV infection conferred
      resistance to chemotherapeutics that induced S-phase arrest by specifically
      inhibiting the activation of CHK2 response signaling in DLBCL.

PMID- 29352125
TI  - Biomolecular regulation, composition and nanoarchitecture of bone mineral.
AB  - Tough natural nanocomposites like bone, nacre and sea sponges contain within
      their hierarchy, a mineral (phosphate, silicate or carbonate) phase that
      interacts with an organic phase. In bone, the role of mineral ultrastructure
      (organization, morphology, composition) is crucial to the mechanical and
      biological properties of the tissue. Better understanding of mineral interaction
      with the organic matrix, in particular non-collagenous proteins, osteocalcin (OC)
      and osteopontin (OPN), can lead to better design of biomimetic materials. Using
      small angle x-ray scattering (SAXS) and wavelength dispersive spectroscopy (WDS)
      on single (OC-/- and OPN-/-) and double (OC-OPN-/-;-/-) genetic knockout mice
      bones, we demonstrate that both osteocalcin and osteopontin have specific roles
      in the biomolecular regulation of mineral in bone and together they are major
      determinants of the quality of bone mineral. Specifically, for the first time, we
      show that proteins osteocalcin and osteopontin regulate bone mineral crystal size
      and organization in a codependent manner, while they independently determine
      crystal shape. We found that OC is more dominant in the regulation of the
      physical properties of bone mineral, while OPN is more dominant in the regulation
      of the mineral composition.

PMID- 29352126
TI  - Role of subcortical structures on cognitive and social function in schizophrenia.
AB  - Subcortical regions have a pivotal role in cognitive, affective, and social
      functions in humans, and the structural and functional abnormalities of the
      regions have been associated with various psychiatric disorders. Although
      previous studies focused on the neurocognitive and socio-functional consequences
      of prefrontal and tempolo-limbic abnormalities in psychiatric disorders, those of
      subcortical structures remain largely unknown. Recently, MRI volume alterations
      in subcortical structures in patients with schizophrenia have been replicated in
      large-scale meta-analytic studies. Here we investigated the relationship between
      volumes of subcortical structures and neurocognitive and socio-functional indices
      in a large sample of patients with schizophrenia. First, we replicated the
      results of meta-analyses: the regional volumes of the bilateral hippocampus,
      amygdala, thalamus and nucleus accumbens were significantly smaller for patients
      (N = 163) than for healthy controls (HCs, N = 620). Second, in the patient group,
      the right nucleus accumbens volume was significantly correlated with the Digit
      Symbol Coding score, which is known as a distinctively characteristic index of
      cognitive deficits in schizophrenia. Furthermore, the right thalamic volume was
      significantly correlated with social function scores. In HCs, no significant
      correlation was found. The results from this large-scale investigation shed light
      upon the role of specific subcortical nuclei on cognitive and social functioning
      in schizophrenia.

PMID- 29352127
TI  - Structural Covariance of Gray Matter Volume in HIV Vertically Infected
      Adolescents.
AB  - Human immunodeficiency virus (HIV) infection significantly affect
      neurodevelopmental and behavioral outcomes. We investigated whether alterations
      of gray matter organization and structural covariance networks with vertical HIV
      infection adolescents exist, by using the GAT toolbox. MRI data were analysed
      from 25 HIV vertically infected adolescents and 33 HIV-exposed-uninfected control
      participants. The gray matter volume (GMV) was calculated, and structural brain
      networks were reconstructed from gray matter co-variance. Gray matter losses were
      pronounced in anterior cingulate cortex (ACC), right pallidum, right occipital
      lobe, inferior parietal lobe, and bilateral cerebellum crus. The global brain
      network measures were not significantly different between the groups; however,
      the nodal alterations were most pronounced in frontal, temporal, basal ganglia,
      cerebellum, and temporal lobes. Brain hubs in the HIV-infected subjects increased
      in number and tended to shift to sensorimotor and temporal areas. In the HIV
      infected subjects, decreased GMVs in ACC and bilateral cerebellum were related to
      lower Mini-Mental State Examination scores; the CD4 counts were positively
      related to the GMVs in ACC and sensorimotor areas. These findings suggest that
      focally reduced gray matter, disrupted nodal profiles of structural wirings, and
      a shift in hub distribution may represent neuroanatomical biomarkers of HIV
      infection on the developing brain.

PMID- 29352129
TI  - Molecular characterization of the grape seeds extract's effect against chemically
      induced liver cancer: In vivo and in vitro analyses.
AB  - The purpose of this study was to investigate the anti-cancer property of grape
      seed extract (GSE) during early stages of developing liver cancer using a two
      stage carcinogenic model combining diethylnitrosamine (DEN) and 2-Acetyl
      Aminofluorene (2-AAF). Administration of GSE at doses 25, 50 and 100 mg/kg per
      day started at the beginning of promotion periods and continued for 14 weeks. GSE
      dramatically inhibited pre-neoplastic foci formation as well as significantly
      decreased the number and the area of placental glutathione-S-transferase in
      livers of DEN-2AAF-treated rats by approximately 4 & 10 fold deductions,
      respectively. GSE's effects were associated with induced apoptosis, reduced cell
      proliferation, decreased oxidative stress and down regulation of histone
      deacetylase activity and inflammation makers, such as cyclooxygenase 2, inducible
      nitric oxide synthase, nuclear factor-kappa B-p65 and p- phosphorylated tumor
      necrosis factor receptor expressions in liver. GSE treatment also decreased the
      viability of HepG2 cells and induced early and late apoptosis through activating
      caspase-3 and Bax. Furthermore, GSE induced G2/M and G1/S cell cycle arrest. The
      present study provides evidence that the GSE's anticancer effect is mediated
      through the inhibition of cell proliferation, induction of apoptosis, modulating
      oxidative damage and suppressing inflammatory response.

PMID- 29352130
TI  - Equal status in Ultimatum Games promotes rational sharing.
AB  - Experiments on the Ultimatum Game (UG) repeatedly show that people's behaviour is
      far from rational. In UG experiments, a subject proposes how to divide a pot and
      the other can accept or reject the proposal, in which case both lose everything.
      While rational people would offer and accept the minimum possible amount, in
      experiments low offers are often rejected and offers are typically larger than
      the minimum, and even fair. Several theoretical works have proposed that these
      results may arise evolutionarily when subjects act in both roles and there is a
      fixed interaction structure in the population specifying who plays with whom. We
      report the first experiments on structured UG with subjects playing
      simultaneously both roles. We observe that acceptance levels of responders
      approach rationality and proposers accommodate their offers to their environment.
      More precisely, subjects keep low acceptance levels all the time, but as
      proposers they follow a best-response-like approach to choose their offers. We
      thus find that status equality promotes rational sharing while the influence of
      structure leads to fairer offers compared to well-mixed populations. Our results
      are far from what is observed in single-role UG experiments and largely different
      from available predictions based on evolutionary game theory.

PMID- 29352128
TI  - Phosphorylation of the Transient Receptor Potential Ankyrin 1 by Cyclin-dependent
      Kinase 5 affects Chemo-nociception.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase that is upregulated
      during inflammation, and can subsequently modulate sensitivity to nociceptive
      stimuli. We conducted an in silico screen for Cdk5 phosphorylation sites within
      proteins whose expression was enriched in nociceptors and identified the chemo
      responsive ion channel Transient Receptor Potential Ankyrin 1 (TRPA1) as a
      possible Cdk5 substrate. Immunoprecipitated full length TRPA1 was shown to be
      phosphorylated by Cdk5 and this interaction was blocked by TFP5, an inhibitor
      that prevents activation of Cdk5. In vitro peptide-based kinase assay revealed
      that four of six TRPA1 Cdk5 consensus sites acted as substrates for Cdk5, and
      modeling of the ankyrin repeats disclosed that phosphorylation would occur at
      characteristic pockets within the (T/S)PLH motifs. Calcium imaging of trigeminal
      ganglion neurons from genetically engineered mice overexpressing or lacking the
      Cdk5 activator p35 displayed increased or decreased responsiveness, respectively,
      to stimulation with the TRPA1 agonist allylisothiocyanate (AITC). AITC-induced
      chemo-nociceptive behavior was also heightened in vivo in mice overexpressing p35
      while being reduced in p35 knockout mice. Our findings demonstrate that TRPA1 is
      a substrate of Cdk5 and that Cdk5 activity is also able to modulate TRPA1 agonist
      induced calcium influx and chemo-nociceptive behavioral responses.

PMID- 29352132
TI  - Design of non-equiatomic medium-entropy alloys.
AB  - High-entropy alloys have attracted much attention due to their unique
      microstructures and excellent properties. Since their invention more than ten
      years ago, research attention has been mainly focused on the study of
      multicomponent alloys with equiatomic or near-equiatomic compositions. Here we
      propose a novel design of non-equiatomic medium-entropy alloys that contain one
      matrix element and several equiatomic alloying elements. To verify the utility of
      this new design, a series of Co-free Fex(CrNiAl)100-x (at.%, 25 <= x <= 65)
      medium-entropy alloys were designed from the much-studied FeNiCrCoAl high-entropy
      alloy. Detailed characterization reveals that the alloys exhibit novel two-phase
      microstructures consisting of B2-ordered nanoprecipitates and BCC-disordered
      matrix. As the alloys deviate far from equiatomic composition, the structure of
      the nanoprecipitates transfers from a spinodal-like intertwined structure to a
      nanoparticle dispersed structure. Previous parametric approaches to predict phase
      formation rules for high-entropy alloys are unable to describe the phase
      separation behaviors in the studied alloys. Our findings provide a new route to
      design medium-entropy alloys and also demonstrate a strategy for designing
      nanostructured alloys from multicomponent alloy systems through simple variations
      in non-equiatomic compositions.

PMID- 29352131
TI  - Early impoverished environment delays the maturation of cerebral cortex.
AB  - The influence of exposure to impoverished environments on brain development is
      unexplored since most studies investigated how environmental impoverishment
      affects adult brain. To shed light on the impact of early impoverishment on
      developmental trajectories of the nervous system, we developed a protocol of
      environmental impoverishment in which dams and pups lived from birth in a
      condition of reduced sensory-motor stimulation. Focusing on visual system, we
      measured two indexes of functional development, that is visual acuity, assessed
      by using Visual Evoked Potentials (VEPs), and VEP latency. In addition, we
      assessed in the visual cortex levels of Insulin-Like Growth Factor 1 (IGF-1) and
      myelin maturation, together with the expression of the GABA biosynthetic enzyme
      GAD67. We found that early impoverishment strongly delays visual acuity and VEP
      latency development. These functional changes were accompanied by a significant
      reduction of IGF-1 protein and GAD67 expression, as well as by delayed
      myelination of nerve fibers, in the visual cortex of impoverished pups. Thus,
      exposure to impoverished living conditions causes a significant alteration of
      developmental trajectories leading to a prominent delay of brain maturation.
      These results underscore the significance of adequate levels of environmental
      stimulation for the maturation of central nervous system.

PMID- 29352133
TI  - Molecular and physiological roles of the adaptor protein CARD9 in immunity.
AB  - CARD9 is a caspase recruitment domain-containing signaling protein that plays a
      critical role in innate and adaptive immunity. It has been widely demonstrated
      that CARD9 adaptor allows pattern recognition receptors to induce NF-kappaB and
      MAPK activation, which initiates a "downstream" inflammation cytokine cascade and
      provides effective protection against microbial invasion, especially fungal
      infection. Here our aim is to update existing paradigms and summarize the most
      recent findings on the CARD9 signaling pathway, revealing significant mechanistic
      insights into the pathogenesis of CARD9 deficiency. We also discuss the effect of
      CARD9 genetic mutations on the in vivo immune response, and highlight clinical
      advances in non-infection inflammation.

PMID- 29352134
TI  - Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces
      pyroptosis in human A459 lung adenocarcinoma cells.
AB  - In order to exploit the rich reservoir of marine cold-adapted bacteria as a
      source of bioactive metabolites, ethyl acetate crude extracts of thirteen polar
      marine bacteria were tested for their antiproliferative activity on A549 lung
      epithelial cancer cells. The crude extract from Pseudoalteromonas haloplanktis
      TAC125 was the most active in inhibiting cell proliferation. Extensive bioassay
      guided purification and mass spectrometric characterization allowed the
      identification of 4-hydroxybenzoic acid (4-HBA) as the molecule responsible for
      this bioactivity. We further demonstrate that 4-HBA inhibits A549 cancer cell
      proliferation with an IC50 value <= 1 MUg ml-1, and that the effect is specific,
      since the other two HBA isomers (i.e. 2-HBA and 3-HBA) were unable to inhibit
      cell proliferation. The effect of 4-HBA is also selective since treatment of
      normal lung epithelial cells (WI-38) with 4-HBA did not affect cell viability.
      Finally, we show that 4-HBA is able to activate, at the gene and protein levels,
      a specific cell death signaling pathway named pyroptosis. Accordingly, the
      treatment of A549 cells with 4-HBA induces the transcription of (amongst others)
      caspase-1, IL1beta, and IL18 encoding genes. Studies needed for the elucidation
      of mode of action of 4-HBA will be instrumental in depicting novel details of
      pyroptosis.

PMID- 29352137
TI  - Iron Biogeochemistry in the High Latitude North Atlantic Ocean.
AB  - Iron (Fe) is an essential micronutrient for marine microbial organisms, and low
      supply controls productivity in large parts of the world's ocean. The high
      latitude North Atlantic is seasonally Fe limited, but Fe distributions and source
      strengths are poorly constrained. Surface ocean dissolved Fe (DFe) concentrations
      were low in the study region (<0.1 nM) in summer 2010, with significant
      perturbations during spring 2010 in the Iceland Basin as a result of an eruption
      of the Eyjafjallajokull volcano (up to 2.5 nM DFe near Iceland) with
      biogeochemical consequences. Deep water concentrations in the vicinity of the
      Reykjanes Ridge system were influenced by pronounced sediment resuspension, with
      indications for additional inputs by hydrothermal vents, with subsequent lateral
      transport of Fe and manganese plumes of up to 250-300 km. Particulate Fe formed
      the dominant pool, as evidenced by 4-17 fold higher total dissolvable Fe compared
      with DFe concentrations, and a dynamic exchange between the fractions appeared to
      buffer deep water DFe. Here we show that Fe supply associated with deep winter
      mixing (up to 103 nmol m-2 d-1) was at least ca. 4-10 times higher than
      atmospheric deposition, diffusive fluxes at the base of the summer mixed layer,
      and horizontal surface ocean fluxes.

PMID- 29352136
TI  - GPhenoVision: A Ground Mobile System with Multi-modal Imaging for Field-Based
      High Throughput Phenotyping of Cotton.
AB  - Imaging sensors can extend phenotyping capability, but they require a system to
      handle high-volume data. The overall goal of this study was to develop and
      evaluate a field-based high throughput phenotyping system accommodating high
      resolution imagers. The system consisted of a high-clearance tractor and sensing
      and electrical systems. The sensing system was based on a distributed structure,
      integrating environmental sensors, real-time kinematic GPS, and multiple imaging
      sensors including RGB-D, thermal, and hyperspectral cameras. Custom software was
      developed with a multilayered architecture for system control and data
      collection. The system was evaluated by scanning a cotton field with 23 genotypes
      for quantification of canopy growth and development. A data processing pipeline
      was developed to extract phenotypes at the canopy level, including height, width,
      projected leaf area, and volume from RGB-D data and temperature from thermal
      images. Growth rates of morphological traits were accordingly calculated. The
      traits had strong correlations (r = 0.54-0.74) with fiber yield and good broad
      sense heritability (H2 = 0.27-0.72), suggesting the potential for conducting
      quantitative genetic analysis and contributing to yield prediction models. The
      developed system is a useful tool for a wide range of breeding/genetic,
      agronomic/physiological, and economic studies.

PMID- 29352135
TI  - Blocking Zika virus vertical transmission.
AB  - The outbreak of the Zika virus (ZIKV) has been associated with increased
      incidence of congenital malformations. Although recent efforts have focused on
      vaccine development, treatments for infected individuals are needed urgently.
      Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C
      (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective
      against ZIKV both in vitro and in vivo. Here, we show that SOF protected human
      neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated
      cell death and importantly restored the antiviral immune response in NPCs. In
      vivo, SOF treatment post-infection (p.i.) decreased viral burden in an
      immunodeficient mouse model. Finally, we show for the first time that acute SOF
      treatment of pregnant dams p.i. was well-tolerated and prevented vertical
      transmission of the virus to the fetus. Taken together, our data confirmed SOF
      mediated sparing of human neural cell types from ZIKV-mediated cell death in
      vitro and reduced viral burden in vivo in animal models of chronic infection and
      vertical transmission, strengthening the growing body of evidence for SOF anti
      ZIKV activity.

PMID- 29352138
TI  - miR-663 sustains NSCLC by inhibiting mitochondrial outer membrane
      permeabilization (MOMP) through PUMA/BBC3 and BTG2.
AB  - Treatment of lung cancer is an unmet need as it accounts for the majority of
      cancer deaths worldwide. The development of new therapies urges the
      identification of potential targets. MicroRNAs' expression is often deregulated
      in cancer and their modulation has been proposed as a successful strategy to
      interfere with tumor cell growth and spread. We recently reported on an unbiased
      high-content approach to identify miRNAs regulating cell proliferation and
      tumorigenesis in non-small cell lung cancer (NSCLC). Here we studied the
      oncogenic role of miR-663 in NSCLC biology and analyzed the therapeutic potential
      of miR-663 targeting. We found that miR-663 regulates apoptosis by controlling
      mitochondrial outer membrane permeabilization (MOMP) through the expression of
      two novel direct targets PUMA/BBC3 and BTG2. Specifically, upon miR-663 knockdown
      the BH3-only protein PUMA/BBC3 directly activates mitochondrial depolarization
      and cell death, while BTG2 accumulation further enhances this effect by
      triggering p53 mitochondrial localization. Moreover, we show that miR-663
      depletion is sufficient to elicit cell death in NSCLC cells and to impair tumor
      growth in vivo.

PMID- 29352139
TI  - Mitochondrial glutamine metabolism via GOT2 supports pancreatic cancer growth
      through senescence inhibition.
AB  - Cellular senescence, which leads to a cell cycle arrest of damaged or
      dysfunctional cells, is an important mechanism to restrain the malignant
      progression of cancer cells. Because metabolic changes underlie many cell-fate
      decisions, it has been suggested that cell metabolism might play key roles in
      senescence pathways. Here, we show that mitochondrial glutamine metabolism
      regulates senescence in human pancreatic ductal adenocarcinoma (PDAC) cells.
      Glutamine deprivation or inhibition of mitochondrial aspartate transaminase
      (GOT2) results in a profound induction of senescence and a suppression of PDAC
      growth. Glutamine carbon flow through GOT2 is required to create NADPH and to
      maintain the cellular redox state. We found that elevated reactive oxygen species
      levels by GOT2 knockdown lead to the cyclin-dependent kinase inhibitor p27
      mediated senescence. Importantly, PDAC cells exhibit distinct dependence on this
      pathway, whereas knockdown of GOT2 did not induce senescence in non-transformed
      cells. The essentiality of GOT2 in senescence regulation of PDAC, which is
      dispensable in their normal counterparts, may have profound implications for the
      development of strategies to treat these refractory cancers.

PMID- 29352140
TI  - Ultra-high Photoresponsivity in Suspended Metal-Semiconductor-Metal Mesoscopic
      Multilayer MoS2 Broadband Detector from UV-to-IR with Low Schottky Barrier
      Contacts.
AB  - The design, fabrication, and characterization of ultra-high responsivity
      photodetectors based on mesoscopic multilayer MoS2 is presented, which is a less
      explored system compared to direct band gap monolayer MoS2 that has received
      increasing attention in recent years. The device architecture is comprised of a
      metal-semiconductor-metal (MSM) photodetector, where Mo was used as the contact
      metal to suspended MoS2 membranes. The photoresponsivity [Formula: see text] was
      measured to be ~1.4 * 104 A/W, which is > 104 times higher compared to prior
      reports, while the detectivity D* was computed to be ~2.3 * 1011 Jones at 300 K
      at an optical power P of ~14.5 pW and wavelength lambda of ~700 nm. In addition,
      the dominant photocurrent mechanism was determined to be the photoconductive
      effect (PCE), while a contribution from the photogating effect was also noted
      from trap-states that yielded a wide spectral photoresponse from UV-to-IR (400 nm
      to 1100 nm) with an external quantum efficiency (EQE) ~104. From time-resolved
      photocurrent measurements, a decay time tau d ~ 2.5 ms at 300 K was measured from
      the falling edge of the photogenerated waveform after irradiating the device with
      a stream of incoming ON/OFF white light pulses.

PMID- 29352141
TI  - Pressure effect on impurity local vibrational mode and phase transitions in n
      type iron-doped indium phosphide.
AB  - The evolution of iron local vibrational mode (Fe LVM) and phase transitions in n
      type iron-doped indium phosphide (InP:Fe) were investigated at ambient
      temperature. In-situ angle-dispersive X-ray diffraction measurements revealed
      that InP:Fe starts to transform from zinc-blende (ZB) to rock-salt (RS) structure
      around 8.2(2) GPa and completes around 16.0(2) GPa. The Raman shift of both
      transverse and longitudinal optical modes increases monotonically with increasing
      pressure, while their intensities become indiscernible at 11.6(2) GPa, suggesting
      that the pressure-induced phase transition is accompanied by significant
      metallization. In contrast, originally absent at ambient pressure, the Raman
      shift of Fe LVM appears at ~420 cm-1 near 1.2 GPa and exhibits a dome shape
      behavior with increasing pressure, reaching a maximum value of ~440 cm-1 around 5
      GPa, with an apparent kink occurring around the ZB-RS transition pressure of
      ~8.5(2) GPa. The Fe K-edge X-ray absorption near edge structure (XANES) confirmed
      the tetrahedral site occupation of Fe3+ with a crystal field splitting parameter
      Delta t  = 38 kJ.mole-1. Our calculations indicate that the energy parameters
      governing the phase transition are Deltat = 0.49 and Delta o  = 1.10 kJ.mole-1,
      respectively, both are much smaller than Delta t  = 38 kJ.mole-1 at ambient.

PMID- 29352142
TI  - FBXL10 contributes to the development of diffuse large B-cell lymphoma by
      epigenetically enhancing ERK1/2 signaling pathway.
AB  - Epigenetic modifiers have emerged as critical factors governing the biology of
      different cancers. Herein we show that FBXL10 (also called KDM2B or JHDM1B), an
      important member of Polycomb repressive complexes, is overexpressed in human
      diffuse large B-cell lymphoma (DLBCL) tissues and the derived cell lines.
      Knocking down FBXL10 by specific short hairpin RNAs in DLBCL cells inhibits cell
      proliferation and induces apoptosis in vitro. Moreover, FBXL10 depletion in DLBCL
      cells abrogates tumor growth in mouse xenograft models. Through the analysis of
      RNA sequencing, we find that one of the key derepressed genes by depletion of
      FBXL10 is DUSP6, encoding a phosphatase for ERK1/2. Mechanistically FBXL10
      maintains the silencing of DUSP6 expression via recruitment of Polycomb group
      proteins and deposition of repressive histone modifications at the DUSP6
      promoter. Consistently, FBXL10 is required for ERK1/2 phosphorylation in DLBCL
      cells. Furthermore, we show that ERK1/2 activation and the proliferation rate of
      FBXL10-depleted cells can be rescued by downregulation of DUSP6 expression. These
      findings indicate that FBXL10 may be a promising therapeutic target in DLBCL and
      establish a link of epigenetic regulators to kinase signaling pathways.

PMID- 29352143
TI  - Ribosomal protein uS7/Rps5 serine-223 in protein kinase-mediated phosphorylation
      and ribosomal small subunit maturation.
AB  - Cellular translation should be precisely controlled in response to extracellular
      cues. However, knowledge is limited concerning signal transduction-regulated
      translation. In the present study, phosphorylation was identified in the 40S
      small subunit ribosomal protein uS7 (Yjr123w/previously called as Rps5) by Ypk1
      and Pkc1, AGC family protein kinases in yeast Saccharomyces cerevisiae. Serine
      residue 223 (Ser223) of uS7 in the conserved C-terminal region was crucial for
      this phosphorylation event. S223A mutant uS7 caused severe reduction of small
      ribosomal subunit production, likely due to compromised interaction with Rio2,
      resulting in both reduced translation and reduced cellular proliferation.
      Contrary to optimal culture conditions, heat stressed S223A mutant cells
      exhibited increased heat resistance and induced heat shock proteins. Taken
      together, an intracellular signal transduction pathway involving Ypk1/Pkc1 seemed
      to play an important role in ribosome biogenesis and subsequent cellular
      translation, utilizing uS7 as a substrate.

PMID- 29352144
TI  - Pressure assisted enhancement in superconducting properties of Fe substituted
      NbSe2 single crystal.
AB  - The impact of hydrostatic pressure (P) up to 1 GPa on T c , J c and the nature of
      the pinning mechanism in FexNbSe2 single crystals have been investigated within
      the framework of the collective theory. We found that the pressure can induce a
      transition from the regime where pinning is controlled by spatial variation in
      the critical transition temperature (deltaT c ) to the regime controlled by
      spatial variation in the mean free path (deltal). Furthermore, T c and low field
      J c are slightly induced, although the J c drops more rapidly at high fields than
      at ambient P. The pressure effect enhances the anisotropy and reduces the
      coherence length, resulting in weak interaction of the vortex cores with the
      pinning centers. Moreover, the P can induce the density of states, which, in
      turn, leads to enhance in T c with increasing P. P enhances the T c with the
      rates of dT c /dP of 0.86, 1.35 and 1.47 K/GPa for FexNbSe2, respectively. The
      magnetization data are used to establish a vortex phase diagram. The nature of
      the vortices has been determined from the scaling behaviour of the pinning force
      density extracted from the J c -H isotherms and demonstrates the point pinning
      mechanism.

PMID- 29352145
TI  - Integrating modality-specific expectancies for the deployment of spatial
      attention.
AB  - The deployment of spatial attention is highly sensitive to stimulus
      predictability. Despite evidence for strong crossmodal links in spatial
      attentional systems, it remains to be elucidated how concurrent but divergent
      predictions for targets in different sensory modalities are integrated. In a
      series of behavioral studies, we investigated the processing of modality-specific
      expectancies using a multimodal cueing paradigm in which auditory cues predicted
      the location of visual or tactile targets with modality-specific cue
      predictability. The cue predictability for visual and tactile targets was
      manipulated independently. A Bayesian ideal observer model with a weighting
      factor was applied to trial-wise individual response speed to investigate how the
      two probabilistic contexts are integrated. Results showed that the degree of
      integration depended on the level of predictability and on the divergence of the
      modality-specific probabilistic contexts (Experiments 1-2). However, when the two
      probabilistic contexts were matched in their level of predictability and were
      highly divergent (Experiment 3), higher separate processing was favored,
      especially when visual targets were processed. These findings suggest that
      modality-specific predictions are flexibly integrated according to their
      reliability, supporting the hypothesis of separate modality-specific attentional
      systems that are however linked to guarantee an efficient deployment of spatial
      attention across the senses.

PMID- 29352146
TI  - Effects of Renal Denervation on Cardiac Structural and Functional Abnormalities
      in Patients with Resistant Hypertension or Diastolic Dysfunction.
AB  - The aim of the present study is to systematically evaluate the impact of RDN on
      cardiac structure and function in patients with resistant hypertension (RH) or
      diastolic dysfunction. We retrieved Pubmed, Embase and Cocharane Library
      databases, from inception to April 1st, 2016. Studies reporting left ventricular
      mass (LVMI) or left ventricular (LV) diastolic function (reflected by the ratio
      of mitral inflow velocity to annular relaxation velocity [E/e']) responses to RDN
      were included. Two randomized controlled trials (RCTs), 3 controlled studies and
      11 uncontrolled studies were finally identified. In observational studies, there
      was a reduction in LVMI, E/e' and N-terminal pro B-type natriuretic peptide (BNP)
      at 6 months, compared with pre-RDN values. LV ejection fraction (LVEF) elevated
      at 6 months following RDN. In RCTs, however, no significant change in LVMI, E/e',
      BNP, left atrial volume index or LVEF was observed at 12 months, compared with
      pharmaceutical therapy. In summary, both LV hypertrophy and cardiac function
      improved at 6 months after RDN. Nonetheless, current evidence failed to show that
      RDN was superior to intensive (optimal) drug therapy in improving cardiac
      remodeling and function.

PMID- 29352148
TI  - Stochastic optimization of broadband reflecting photonic structures.
AB  - Photonic crystals (PCs) are built to control the propagation of light within
      their structure. These can be used for an assortment of applications where custom
      designed devices are of interest. Among them, one-dimensional PCs can be produced
      to achieve the reflection of specific and broad wavelength ranges. However, their
      design and fabrication are challenging due to the diversity of periodic
      arrangement and layer configuration that each different PC needs. In this study,
      we present a framework to design high reflecting PCs for any desired wavelength
      range. Our method combines three stochastic optimization algorithms (Random
      Search, Particle Swarm Optimization and Simulated Annealing) along with a reduced
      space-search methodology to obtain a custom and optimized PC configuration. The
      optimization procedure is evaluated through theoretical reflectance spectra
      calculated by using the Equispaced Thickness Method, which improves the
      simulations due to the consideration of incoherent light transmission. We prove
      the viability of our procedure by fabricating different reflecting PCs made of
      porous silicon and obtain good agreement between experiment and theory using a
      merit function. With this methodology, diverse reflecting PCs can be designed for
      any applications and fabricated with different materials.

PMID- 29352147
TI  - Pre-conception maternal erythrocyte saturated to unsaturated fatty acid ratio
      predicts pregnancy after natural cycle frozen embryo transfer.
AB  - The environment for embryo implantation and fetal growth and development is
      affected by maternal nutritional, metabolic and health status. The aim of this
      prospective, cohort study was to test whether plasma metabolic and inflammatory
      biomarkers can predict pregnancy resulting from in vitro fertilisation (IVF).
      Women with a natural menstrual cycle undergoing frozen embryo transfer (FET) were
      recruited and fasting baseline blood samples were collected a mean of 3.4 days
      prior to the luteinising hormone (LH) surge and a non-fasting blood sample was
      taken on the day of FET. Ongoing pregnancy was defined by positive fetal
      heartbeat on ultrasound scan at day 45 post LH surge. Thirty-six pregnancies
      resulted from FET in 143 women. In an overall stepwise multivariable analysis,
      erythrocyte saturated to unsaturated fatty acid ratio was positively associated
      with ongoing pregnancy. A similar model incorporating day of FET covariates found
      that erythrocyte saturated to unsaturated fatty acid ratio, erythrocyte fatty
      acid average chain length and plasma log-triglycerides predicted ongoing
      pregnancy. In conclusion, a higher peri-conceptional saturated to unsaturated
      fatty acid ratio predicted ongoing pregnancy after natural cycle frozen embryo
      transfer and may reflect a maternal nutritional status that facilitates pregnancy
      success in this assisted conception scenario.

PMID- 29352149
TI  - Spin Hall-induced auto-oscillations in ultrathin YIG grown on Pt.
AB  - We experimentally study nanowire-shaped spin-Hall nano-oscillators based on
      nanometer-thick epitaxial films of Yttrium Iron Garnet grown on top of a layer of
      Pt. We show that, although these films are characterized by significantly larger
      magnetic damping in comparison with the films grown directly on Gadolinium
      Gallium Garnet, they allow one to achieve spin current-driven auto-oscillations
      at comparable current densities, which can be an indication of the better
      transparency of the interface to the spin current. These observations suggest a
      route for improvement of the flexibility of insulator-based spintronic devices
      and their compatibility with semiconductor technology.

PMID- 29352150
TI  - Identification and quantification of plasma calciprotein particles with distinct
      physical properties in patients with chronic kidney disease.
AB  - Calciprotein particles (CPP) are solid-phase calcium-phosphate bound to serum
      protein fetuin-A and dispersed as colloids in the blood. Recent clinical studies
      indicated that serum CPP levels were increased with decline of renal function and
      associated with inflammation and vascular calcification. However, CPP assays used
      in these studies measured only a part of CPP over a certain particle size and
      density. Here we show that such CPP are mostly artifacts generated during
      processing of serum samples in vitro. The native CPP in fresh plasma are smaller
      in size and lower in density than those artifactual CPP, composed of fetuin-A
      carrying amorphous and/or crystalline calcium-phosphate, and increased primarily
      with serum phosphate levels. We have identified several physicochemical factors
      that promote aggregation/dissolution of CPP and transition of the calcium
      phosphate from the amorphous phase to the crystalline phase in vitro, including
      addition of anti-coagulants, composition of buffer for sample dilution, the
      number of freeze-thaw cycles, the speed for sample freezing, and how many hours
      the samples were left at what temperature. Therefore, it is of critical
      importance to standardize these factors during sample preparation in clinical
      studies on CPP and to investigate the biological activity of the native CPP.

PMID- 29352152
TI  - Selection and validation of reference genes for qRT-PCR analysis of gene
      expression in Microsporum canis growing under different adhesion-inducing
      conditions.
AB  - Dermatophytes are the group of filamentous fungi infecting keratinized structures
      such as skin, hair, and nails. Knowledge about genes and molecular mechanisms
      responsible for pathogenicity, as well as other biological properties of
      Microsporum canis is still relatively poor. The qRT-PCR is a reliable technique
      for quantifying gene expression across various biological processes, and choosing
      a set of suitable reference genes to normalize the expression data is a crucial
      step of this technique. We investigated the suitability of nine candidate
      reference genes: beta-act, beta-tub, adp-rf, ef1-alpha, sdha, rpl2, mbp1, psm1,
      and rGTPa for gene expression analysis in the dermatophyte M. canis in response
      to different carbon sources, phosphate levels, and pH shifts - factors that are
      extremely important and necessary for growth of dermatophyte in the host tissue.
      The transcription stability of these genes was evaluated using NormFinder,
      geNorm, BestKeeper, and RefFinder software. Regarding expression stability, mbp1,
      beta-act, and sdha were the most stable housekeeping genes which we recommend for
      future qRT-PCR studies on M. canis strains. To the best of our knowledge this is
      the first study on selection and validation of reference genes for qRT-PCR data
      normalization in M. canis growth in culture media which promote adhesion-inducing
      conditions.

PMID- 29352151
TI  - Effects of genetic variants on platelet reactivity and one-year clinical outcomes
      after percutaneous coronary intervention: A prospective multicentre registry
      study.
AB  - Clopidogrel is the mainstay for antiplatelet treatment after percutaneous
      coronary intervention (PCI). The relationship of platelet reactivity and genetic
      polymorphism with clinical outcomes with newer-generation drug-eluting stents is
      unclear. We analysed 4,587 patients for the most powerful single-nucleotide
      polymorphisms (CYP2C19, CYP2C9, ABCB1, PON1, and P2Y12) related to on-treatment
      platelet reactivity (OPR). The optimal cut-off value of high OPR for major
      adverse thrombotic events was 266. CYP2C19 was significantly associated with high
      OPR and the number of CYP2C19*R (*2 or *3) alleles was proportional to the
      increased risk of high OPR. Death, myocardial infarction (MI), stroke, stent
      thrombosis, and bleeding events were assessed during a 1-year follow-up period.
      Primary endpoints were death and non-fatal MI. The cumulative 1-year incidence of
      death and stent thrombosis was significantly higher in patients with
      CYP2C19*2/*2, CYP2C19*2/*3, and CYP2C19*3/*3 (Group 3) than in patients with
      CYP2C19*1/*1 (Group 1). Multivariate Cox proportional hazard model showed that
      cardiac death risk was significantly higher in Group 3 than in Group 1 (hazard
      ratio 2.69, 95% confidence interval 1.154-6.263, p = 0.022). No association was
      reported between bleeding and OPR. Thus, CYP2C19 may exert a significant impact
      on the prognosis of PCI patients even in the era of newer-generation drug-eluting
      stents.

PMID- 29352153
TI  - Biology-Culture Co-evolution in Finite Populations.
AB  - Language is the result of two concurrent evolutionary processes: biological and
      cultural inheritance. An influential evolutionary hypothesis known as the moving
      target problem implies inherent limitations on the interactions between our two
      inheritance streams that result from a difference in pace: the speed of cultural
      evolution is thought to rule out cognitive adaptation to culturally evolving
      aspects of language. We examine this hypothesis formally by casting it as as a
      problem of adaptation in time-varying environments. We present a mathematical
      model of biology-culture co-evolution in finite populations: a generalisation of
      the Moran process, treating co-evolution as coupled non-independent Markov
      processes, providing a general formulation of the moving target hypothesis in
      precise probabilistic terms. Rapidly varying culture decreases the probability of
      biological adaptation. However, we show that this effect declines with population
      size and with stronger links between biology and culture: in realistically sized
      finite populations, stochastic effects can carry cognitive specialisations to
      fixation in the face of variable culture, especially if the effects of those
      specialisations are amplified through cultural evolution. These results support
      the view that language arises from interactions between our two major inheritance
      streams, rather than from one primary evolutionary process that dominates
      another.

PMID- 29352154
TI  - Resting state brain networks in the prairie vole.
AB  - Resting state functional magnetic resonance imaging (rsfMRI) has shown the
      hierarchical organization of the human brain into large-scale complex networks,
      referred as resting state networks. This technique has turned into a promising
      translational research tool after the finding of similar resting state networks
      in non-human primates, rodents and other animal models of great value for
      neuroscience. Here, we demonstrate and characterize the presence of resting
      states networks in Microtus ochrogaster, the prairie vole, an extraordinary
      animal model to study complex human-like social behavior, with potential
      implications for the research of normal social development, addiction and
      neuropsychiatric disorders. Independent component analysis of rsfMRI data from
      isoflurane-anestethized prairie voles resulted in cortical and subcortical
      networks, including primary motor and sensory networks, but also included
      putative salience and default mode networks. We further discuss how future
      research could help to close the gap between the properties of the large scale
      functional organization and the underlying neurobiology of several aspects of
      social cognition. These results contribute to the evidence of preserved resting
      state brain networks across species and provide the foundations to explore the
      use of rsfMRI in the prairie vole for basic and translational research.

PMID- 29352155
TI  - Conflict-sensitive neurons gate interocular suppression in human visual cortex.
AB  - Neural suppression plays an important role in cortical function, including
      sensory, memory, and motor systems. It remains, however, relatively poorly
      understood. A paradigmatic case arises when conflicting images are presented to
      the two eyes. These images can compete for awareness, and one is usually strongly
      suppressed. The mechanisms that resolve such interocular conflict remain unclear.
      Suppression could arise solely from "winner-take-all" competition between neurons
      responsive to each eye. Alternatively, suppression could also depend upon neurons
      detecting interocular conflict. Here, we provide physiological evidence in human
      visual cortex for the latter: suppression depends upon conflict-sensitive
      neurons. We recorded steady-state visual evoked potentials (SSVEP), and used the
      logic of selective adaptation. The amplitude of SSVEP responses at
      intermodulation frequencies strengthened as interocular conflict in the stimulus
      increased, suggesting the presence of neurons responsive to conflict. Critically,
      adaptation to conflict both reduced this SSVEP effect, and increased the amount
      of conflict needed to produce perceptual suppression. The simplest account of
      these results is that interocular-conflict-sensitive neurons exist in human
      cortex: adaptation likely reduced the responsiveness of these neurons which in
      turn raised the amount of conflict required to produce perceptual suppression.
      Similar mechanisms may be used to resolve other varieties of perceptual conflict.

PMID- 29352156
TI  - Comprehensive reduction of amino acid set in a protein suggests the importance of
      prebiotic amino acids for stable proteins.
AB  - Modern organisms commonly use the same set of 20 genetically coded amino acids
      for protein synthesis with very few exceptions. However, earlier protein
      synthesis was plausibly much simpler than modern one and utilized only a limited
      set of amino acids. Nevertheless, few experimental tests of this issue with
      arbitrarily chosen amino acid sets had been reported prior to this report. Herein
      we comprehensively and systematically reduced the size of the amino acid set
      constituting an ancestral nucleoside kinase that was reconstructed in our
      previous study. We eventually found that two convergent sequences, each comprised
      of a 13-amino acid alphabet, folded into soluble, stable and catalytically active
      structures, even though their stabilities and activities were not as high as
      those of the parent protein. Notably, many but not all of the reduced-set amino
      acids coincide with those plausibly abundant in primitive Earth. The inconsistent
      amino acids appeared to be important for catalytic activity but not for
      stability. Therefore, our findings suggest that the prebiotically abundant amino
      acids were used for creating stable protein structures and other amino acids with
      functional side chains were recruited to achieve efficient catalysis.

PMID- 29352157
TI  - Prevalence of parenthood in wheelchair-dependent persons with long-term spinal
      cord injury in the Netherlands.
AB  - STUDY DESIGN: Multicenter  cross-sectional study. OBJECTIVES: To determine the
      prevalence of parenthood in long-term wheelchair-dependent persons who sustained
      a spinal cord injury (SCI) during their reproductive years. Secondary aims were
      to (1) explore patient-specific and disease-related factors associated with
      parenthood after SCI; and (2) quantify fertility aids used by men with SCI.
      SETTING: Eight specialized SCI rehabilitation centers in the Netherlands.
      METHODS: Questionnaires and physical examination were applied in 255 persons with
      SCI. Prevalence rates of parenthood among the general Dutch population were used
      for comparison. Logistic regression analyses were used to explore factors
      associated with parenthood after SCI. RESULTS: Prevalence of parenthood in SCI
      was 50% in men and 45% in women, which was significantly (P < 0.05) lower than
      rates in the general population (74% in men and 81% in women). Among the parents
      with SCI, most (66% of males and 72% of females) of them had children after SCI.
      Parenting children after SCI was associated with partnership (OR = 14.5, P < .001
      [men]; OR = 3.7, P = .05 [women]), normal micturition (OR = 4.9, P = .02 [men]),
      incomplete lesion (OR = 5.4, P = .03 [women]), and paraplegia (OR = 7.3, P = .02
      [women]). The most frequently used methods for ejaculation and fertilization were
      electroejaculation (29%) and intracytoplasmatic sperm injection (23%).
      CONCLUSIONS: Prevalence of parenthood in SCI persons is low. However, half of the
      persons with SCI do become parents, with most doing so following SCI. Demographic
      and disease-related factors may contribute to this.

PMID- 29352158
TI  - Fabrication of multiple nanopores in a SiNx membrane via controlled breakdown.
AB  - This paper reports a controlled breakdown (CBD) method to fabricate multiple
      nanopores in a silicon nitride (SiNx) membrane with control over both nanopore
      count and nanopore diameter. Despite the stochastic process of the breakdown, we
      found that the nanopores created via CBD, tend to be of the same diameter. We
      propose a membrane resistance model to explain and control the multiple nanopores
      forming in the membrane. We prove that the membrane resistance can reflect the
      number of nanopores in the membrane and that the diameter of the nanopores is
      controlled by the exposure time and strength of the electric field. This
      controllable multiple nanopore formation via CBD avoids the utilization of
      complicated instruments and time-intensive manufacturing. We anticipate CBD has
      the potential to become a nanopore fabrication technique which, integrated into
      an optical setup, could be used as a high-throughput and multichannel
      characterization technique.

PMID- 29352159
TI  - 3,3'-Diaminobenzidine staining interferes with PCR-based DNA analysis.
AB  - 3,3'-Diaminobenzidine (DAB) is a widely used chromogen in histological staining
      methods and stained tissue is often used in downstream molecular analyses such as
      quantitative PCR (qPCR). Using microdissected muscle fibers from sequential
      muscle sections stained by DAB-dependent and -independent methods, we show that
      DAB exerts a strong inhibitory effect on qPCR-based mitochondrial DNA
      quantification. This effect introduces a significant bias in the estimation of
      mitochondrial DNA copy number and deletion levels between DAB-positive and 
      negative fibers. We reproduce our findings in microdissected neurons from human
      brain tissue, suggesting a general effect of DAB staining on PCR analyses
      independent of the underlying tissue or cell type. Using an exogenous DNA
      template added to tissue samples we provide evidence that DAB-staining
      predominantly interferes with the tissue-derived DNA template rather than
      inhibiting DNA polymerase activity. Our results suggest that DAB-based staining
      is incompatible with PCR-based quantification methods and some of the previously
      reported results employing this approach should be reconsidered.

PMID- 29352160
TI  - The 'forma specialis' issue in Fusarium: A case study in Fusarium solani f. sp.
      pisi.
AB  - The Fusarium solani species complex (FSSC) has been studied intensively but its
      association with legumes, particularly under European agro-climatic conditions,
      is still poorly understood. In the present study, we investigated phylogenetic
      relationships and aggressiveness of 79 isolates of the FSSC collected from pea,
      subterranean clover, white clover and winter vetch grown under diverse agro
      climatic and soil conditions within Temperate and Mediterranean Europe. The
      isolates were characterized by sequencing tef1 and rpb2 loci and by greenhouse
      aggressiveness assays. The majority of the isolates belonged to two lineages: the
      F. pisi comb. nov. lineage (formerly F. solani f. sp. pisi) mainly accommodating
      German and Swiss isolates, and the Fusisporium (Fusarium) solani lineage
      accommodating mainly Italian isolates. Based on the results of aggressiveness
      tests on pea, most of the isolates were classified as weakly to moderately
      aggressive. In addition, using one model strain, 62 accessions of 10 legume
      genera were evaluated for their potential to host F. pisi, the species known
      mainly as a pathogen of pea. A total of 58 accessions were colonized, with 25 of
      these being asymptomatic hosts. These results suggest a broad host range for F.
      pisi and challenge the forma specialis naming system in Fusarium.

PMID- 29352161
TI  - The action of a negative allosteric modulator at the dopamine D2 receptor is
      dependent upon sodium ions.
AB  - Sodium ions (Na+) allosterically modulate the binding of orthosteric agonists and
      antagonists to many class A G protein-coupled receptors, including the dopamine
      D2 receptor (D2R). Experimental and computational evidences have revealed that
      this effect is mediated by the binding of Na+ to a conserved site located beneath
      the orthosteric binding site (OBS). SB269652 acts as a negative allosteric
      modulator (NAM) of the D2R that adopts an extended bitopic pose, in which the
      tetrahydroisoquinoline moiety interacts with the OBS and the indole-2-carboxamide
      moiety occupies a secondary binding pocket (SBP). In this study, we find that the
      presence of a Na+ within the conserved Na+-binding pocket is required for the
      action of SB269652. Using fragments of SB269652 and novel full-length analogues,
      we show that Na+ is required for the high affinity binding of the
      tetrahydroisoquinoline moiety within the OBS, and that the interaction of the
      indole-2-carboxamide moiety with the SBP determines the degree of Na+
      sensitivity. Thus, we extend our understanding of the mode of action of this
      novel class of NAM by showing it acts synergistically with Na+ to modulate the
      binding of orthosteric ligands at the D2R, providing opportunities for fine
      tuning of modulatory effects in future allosteric drug design efforts.

PMID- 29352162
TI  - A prolonged run-in period of standard subcutaneous microdialysis ameliorates
      quality of interstitial glucose signal in patients after major cardiac surgery.
AB  - We evaluated a standard subcutaneous microdialysis technique for glucose
      monitoring in two critically ill patient populations and tested whether a
      prolonged run-in period improves the quality of the interstitial glucose signal.
      20 surgical patients after major cardiac surgery (APACHE II score: 10.1 +/- 3.2)
      and 10 medical patients with severe sepsis (APACHE II score: 31.1 +/- 4.3) were
      included in this investigation. A microdialysis catheter was inserted in the
      subcutaneous adipose tissue of the abdominal region. Interstitial fluid and
      arterial blood were sampled in hourly intervals to analyse glucose
      concentrations. Subcutaneous adipose tissue glucose was prospectively calibrated
      to reference arterial blood either at hour 1 or at hour 6. Median absolute
      relative difference of glucose (MARD), calibrated at hour 6 (6.2 (2.6; 12.4) %)
      versus hour 1 (9.9 (4.2; 17.9) %) after catheter insertion indicated a
      significant improvement in signal quality in patients after major cardiac surgery
      (p < 0.001). Prolonged run-in period revealed no significant improvement in
      patients with severe sepsis, but the number of extreme deviations from the blood
      plasma values could be reduced. Improved concurrence of glucose readings via a 6
      hour run-in period could only be achieved in patients after major cardiac
      surgery.

PMID- 29352163
TI  - Word Mode: a crowding-free reading protocol for individuals with macular disease.
AB  - Central retinal loss through macular disease markedly reduces the ability to read
      largely because identification of a word using peripheral vision is negatively
      influenced by nearby text, a phenomenon termed visual crowding. Here, we present
      a novel peripheral reading protocol, termed Word Mode, that eliminates crowding
      by presenting each word in isolation but in a position that mimics its natural
      position in the line of text being read, with each new word elicited using a self
      paced button press. We used a gaze-contingent paradigm to simulate a central
      scotoma in four normally-sighted observers, and measured oral reading speed for
      text positioned 7.5 degrees  in the inferior field. Compared with reading whole
      sentences, our crowding-free protocol increased peripheral reading speeds by up
      to a factor of seven, resulted in significantly fewer reading errors and
      fixations per sentence, and reduced both the critical print size and the text
      size required for spot reading by 0.2-0.3 logMAR. We conclude that the level of
      reading efficiency afforded by the crowding-free reading protocol Word Mode may
      return reading as a viable activity to many individuals with macular disease.

PMID- 29352164
TI  - Determinants of breast size in Asian women.
AB  - Breast size as a risk factor of breast cancer has been studied extensively with
      inconclusive results. Here we examined the associations between breast size and
      breast cancer risk factors in 24,353 Asian women aged 50 to 64 years old enrolled
      in a nationwide mammography screening project conducted between October 1994 and
      February 1997. Information on demographic and reproductive factors was obtained
      via a questionnaire. Breast size was ascertained as bust line measured at study
      recruitment and total breast area measured from a mammogram. The average bust
      line and total breast area was 91.2 cm and 102.3 cm2, respectively. The two
      breast measurements were moderately correlated (Spearman correlation coefficient
      = 0.65). Age, BMI, marital and working status were independently associated with
      bust line and total breast area. In the multivariable analyses, the most
      pronounced effects were observed for BMI (24.2 cm difference in bust line and
      39.4 cm2 in breast area comparing women with BMI >=30 kg/m2 to BMI <20 kg/m2).
      Ethnicity was a positive predictor for total breast area, but not bust line.

PMID- 29352165
TI  - Construction of full-length Japanese reference panel of class I HLA genes with
      single-molecule, real-time sequencing.
AB  - Human leukocyte antigen (HLA) is a gene complex known for its exceptional
      diversity across populations, importance in organ and blood stem cell
      transplantation, and associations of specific alleles with various diseases. We
      constructed a Japanese reference panel of class I HLA genes (ToMMo HLA panel),
      comprising a distinct set of HLA-A, HLA-B, HLA-C, and HLA-H alleles, by single
      molecule, real-time (SMRT) sequencing of 208 individuals included in the 1070
      whole-genome Japanese reference panel (1KJPN). For high-quality allele
      reconstruction, we developed a novel pipeline, Primer-Separation Assembly and
      Refinement Pipeline (PSARP), in which the SMRT sequencing and additional short
      read data were used. The panel consisted of 139 alleles, which were all extended
      from known IPD-IMGT/HLA sequences, contained 40 with novel variants, and captured
      more than 96.5% of allelic diversity in 1KJPN. These newly available sequences
      would be important resources for research and clinical applications including
      high-resolution HLA typing, genetic association studies, and analyzes of cis
      regulatory elements.

PMID- 29352166
TI  - Epstein-Barr virus encoded latent membrane protein 1 suppresses necroptosis
      through targeting RIPK1/3 ubiquitination.
AB  - Necroptosis is an alternative programmed cell death pathway that is unleashed in
      the absence of apoptosis and mediated by signaling complexes containing receptor
      interating protein kinase 1 (RIPK1) and RIPK3. This form of cell death has
      recently been implicated in host defense system to eliminate pathogen-infected
      cells. However, only a few viral species such as herpes simplex virus (HSV) and
      cytomegalovirus (CMV) have evolved mechanisms inhibiting necroptosis to overcome
      host antiviral defense, which is important for successful pathogenesis. Here, we
      show that the gamma-herpesvirus Epstein-Barr virus (EBV) blocks necroptosis in
      EBV-infected human nasopharyngeal epithelial cells and nasopharyngeal carcinoma
      cells. Our findings indicate that EBV-encoded latent membrane protein 1 (LMP1),
      which lacks an RIP homotypic interaction motif (RHIM) domain, has mechanisms
      distinct from RHIM signaling competition to inhibit this necroptotic pathway.
      Intriguingly, LMP1 interacts directly with both RIPK1 and RIPK3 through its C
      terminal activation region. More importantly, LMP1 can modulate the post
      translational modification of the two receptor-interacting proteins. We then show
      that LMP1-mediated promotion of K63-polyubiquitinated RIPK1, suppression of RIPK1
      protein expression and inhibition of K63-polyubiquitinated RIPK3 induced a switch
      in cell fate from necroptotic death to survival. These findings provide direct
      evidence for the suppression of necroptosis by EBV and define a mechanism of LMP1
      to interrupt the initiation process of necroptosis before necrosome formation.

PMID- 29352167
TI  - SREBP1c mediates the effect of acetaldehyde on Cidea expression in Alcoholic
      fatty liver Mice.
AB  - Cell death inducing DNA fragmentation factor-alpha-like A (Cidea) is a member of
      cell death-inducing DFF45-like effector (CIDE) protein. The initial function of
      CIDE is the promotion of cell death and DNA fragmentation in mammalian cells.
      Cidea was recently reported to play critical roles in the development of hepatic
      steatosis. The purpose of present study is to determine the effect of chronic
      alcohol intake on Cidea expression in the livers of mice with alcoholic fatty
      liver disease. Cidea expression was significantly increased in the liver of
      alcohol-induced fatty liver mice. While, knockdown of Cidea caused lipid droplets
      numbers reduction. Next, we detected the activity of ALDH2 reduction and the
      concentration of serum acetaldehyde accumulation in our alcohol-induced fatty
      liver mice. Cidea expression was elevated in AML12 cells exposed to 100uM
      acetaldehyde. Interestingly, Dual-luciferase reporter gene assay showed that 100
      uM acetaldehyde led to the activation of Cidea reporter gene plasmid which
      containing SRE element. What's more, the knockdown of SREBP1c suppressed
      acetaldehyde-induced Cidea expression. Overall, our findings suggest that Cidea
      is highly associated with alcoholic fatty liver disease and Cidea expression is
      specifically induced by acetaldehyde, and this up-regulation is most likely
      mediated by SREBP1c.

PMID- 29352169
TI  - Chaski, a novel Drosophila lactate/pyruvate transporter required in glia cells
      for survival under nutritional stress.
AB  - The intercellular transport of lactate is crucial for the astrocyte-to-neuron
      lactate shuttle (ANLS), a model of brain energetics according to which neurons
      are fueled by astrocytic lactate. In this study we show that the Drosophila
      chaski gene encodes a monocarboxylate transporter protein (MCT/SLC16A) which
      functions as a lactate/pyruvate transporter, as demonstrated by heterologous
      expression in mammalian cell culture using a genetically encoded FRET nanosensor.
      chaski expression is prominent in the Drosophila central nervous system and it is
      particularly enriched in glia over neurons. chaski mutants exhibit defects in a
      high energy demanding process such as synaptic transmission, as well as in
      locomotion and survival under nutritional stress. Remarkably, locomotion and
      survival under nutritional stress defects are restored by chaski expression in
      glia cells. Our findings are consistent with a major role for intercellular
      lactate shuttling in the brain metabolism of Drosophila.

PMID- 29352168
TI  - Epigenetic control of influenza virus: role of H3K79 methylation in interferon
      induced antiviral response.
AB  - Influenza virus stablishes a network of virus-host functional interactions, which
      depends on chromatin dynamic and therefore on epigenetic modifications. Using an
      unbiased search, we analyzed the epigenetic changes at DNA methylation and post
      translational histone modification levels induced by the infection. DNA
      methylation was unaltered, while we found a general decrease on histone
      acetylation, which correlates with transcriptional inactivation and may cooperate
      with the impairment of cellular transcription that causes influenza virus
      infection. A particular increase in H3K79 methylation was observed and the use of
      an inhibitor of the specific H3K79 methylase, Dot1L enzyme, or its silencing,
      increased influenza virus replication. The antiviral response was reduced in
      conditions of Dot1L downregulation, since decreased nuclear translocation of NF
      kB complex, and IFN-beta, Mx1 and ISG56 expression was detected. The data
      suggested a control of antiviral signaling by methylation of H3K79 and
      consequently, influenza virus replication was unaffected in IFN pathway
      compromised, Dot1L-inhibited cells. H3K79 methylation also controlled replication
      of another potent interferon-inducing virus such as vesicular stomatitis virus,
      but did not modify amplification of respiratory syncytial virus that poorly
      induces interferon signaling. Epigenetic methylation of H3K79 might have an
      important role in controlling interferon-induced signaling against viral
      pathogens.

PMID- 29352170
TI  - Plasma proteomic study of acute mountain sickness susceptible and resistant
      individuals.
AB  - Although extensive studies have focused on the development of acute mountain
      sickness (AMS), the exact mechanisms of AMS are still obscure. In this study, we
      used isobaric tags for relative and absolute quantitation (iTRAQ) proteomic
      analysis to identify novel AMS-associated biomarkers in human plasma. After 9
      hours of hypobaric hypoxia the abundance of proteins related to tricarboxylic
      acid (TCA) cycle, glycolysis, ribosome, and proteasome were significantly reduced
      in AMS resistant (AMS-) group, but not in AMS susceptible (AMS+) group. This
      suggested that AMS- individuals could reduce oxygen consumption via repressing
      TCA cycle and glycolysis, and reduce energy consumption through decreasing
      protein degradation and synthesis compared to AMS+ individuals after acute
      hypoxic exposure. The inflammatory response might be decreased resulting from the
      repressed TCA cycle. We propose that the ability for oxygen consumption reduction
      may play an important role in the development of AMS. Our present plasma
      proteomic study in plateau of the Han Chinese volunteers gives new data to
      address the development of AMS and potential AMS correlative biomarkers.

PMID- 29352172
TI  - Hemoglobin catalyzes CoA degradation and thiol addition to flavonoids.
AB  - In the presence of CoA, cell-free extracts prepared from porcine liver was found
      to convert 7,8-dihydroxyflavone (DHF) to a pantetheine conjugate, which was a
      novel flavonoid. We purified a 7,8-DHF-converting enzyme from the extracts, and
      identified it as hemoglobin (Hb). The purified Hb showed the following two
      activities: (i) degradation of CoA into pantetheine through hydrolytic cleavage
      to yield pantetheine and 3'-phospho-adenosine-5'-diphosphate (ADP) independently
      of heme, and (ii) addition of a thiol (e.g., pantetheine, glutathione and
      cysteine) to 7,8-DHF through C-S bond formation. Human Hb also exhibited the
      above flavonoid-converting activity. In addition, heme-containing enzymes such as
      peroxidase and catalase added each of pantetheine, glutathione and cysteine to
      the flavonoid, although no pantetheine conjugates were synthesized when CoA was
      used as a substrate. These findings indicated that the thiol-conjugating activity
      is widely observed in heme-containing proteins. On the other hand, only Hb
      catalyzed the hydrolysis of CoA, followed by the thiol conjugation to synthesize
      the pantetheine conjugate. To the best of our knowledge, this is the first report
      showing that Hb has the catalytic ability to convert naturally occurring
      bioactive compounds, such as dietary flavonoids, to the corresponding conjugates
      in the presence of thiol donors or CoA.

PMID- 29352171
TI  - A urine-dependent human urothelial organoid offers a potential alternative to
      rodent models of infection.
AB  - Murine models describe a defined host/pathogen interaction for urinary tract
      infection, but human cell studies are scant. Although recent human urothelial
      organoid models are promising, none demonstrate long-term tolerance to urine, the
      natural substrate of the tissue and of the uropathogens that live there. We
      developed a novel human organoid from progenitor cells which demonstrates key
      structural hallmarks and biomarkers of the urothelium. After three weeks of
      transwell culture with 100% urine at the apical interface, the organoid
      stratified into multiple layers. The apical surface differentiated into enlarged
      and flattened umbrella-like cells bearing characteristic tight junctions,
      structures resembling asymmetric unit membrane plaques, and a glycosaminoglycan
      layer. The apical cells also expressed cytokeratin-20, a spatial feature of the
      mammalian urothelium. Urine itself was necessary for full development, and
      undifferentiated cells were urine-tolerant despite the lack of membrane plaques
      and a glycosaminoglycan layer. Infection with Enterococcus faecalis revealed the
      expected invasive outcome, including urothelial sloughing and the formation of
      intracellular colonies similar to those previously observed in patient cells.
      This new biomimetic model could help illuminate invasive behaviours of
      uropathogens, and serve as a reproducible test bed for disease formation,
      treatment and resolution in patients.

PMID- 29352173
TI  - Maize chlorotic mottle virus exhibits low divergence between differentiated
      regional sub-populations.
AB  - Maize chlorotic mottle virus has been rapidly spreading around the globe over the
      past decade. The interactions of maize chlorotic mottle virus with Potyviridae
      viruses causes an aggressive synergistic viral condition - maize lethal necrosis,
      which can cause total yield loss. Maize production in sub-Saharan Africa, where
      it is the most important cereal, is threatened by the arrival of maize lethal
      necrosis. We obtained maize chlorotic mottle virus genome sequences from across
      East Africa and for the first time from Ecuador and Hawaii, and constructed a
      phylogeny which highlights the similarity of Chinese to African isolates, and
      Ecuadorian to Hawaiian isolates. We used a measure of clustering, the adjusted
      Rand index, to extract region-specific SNPs and coding variation that can be used
      for diagnostics. The population genetics analysis we performed shows that the
      majority of sequence diversity is partitioned between populations, with diversity
      extremely low within China and East Africa.

PMID- 29352174
TI  - Mechanical phenotyping of K562 cells by the Micropipette Aspiration Technique
      allows identifying mechanical changes induced by drugs.
AB  - Mechanical properties of living cells can be used as reliable markers of their
      state, such as the presence of a pathological state or their differentiation
      phase. The mechanical behavior of cells depends on the organization of their
      cytoskeletal network and the main contribution typically comes from the
      actomyosin contractile system, in both suspended and adherent cells. In the
      present study, we investigated the effect of a pharmaceutical formulation (OTC -
      Ossitetraciclina liquida 20%) used as antibiotic, on the mechanical properties of
      K562 cells by using the Micropipette Aspiration Technique (MAT). This formulation
      has been shown to increase in a time dependent way the inflammation and toxicity
      in terms of apoptosis in in vitro experiments on K562 and other types of cells.
      Here we show that by measuring the mechanical properties of cells exposed to OTC
      for different incubation times, it is possible to infer modifications induced by
      the formulation to the actomyosin contractile system. We emphasize that this
      system is involved in the first stages of the apoptotic process where an increase
      of the cortical tension leads to the formation of blebs. We discuss the possible
      relation between the observed mechanical behavior of cells aspirated inside a
      micropipette and apoptosis.

PMID- 29352175
TI  - Magnetic Vortices as Efficient Nano Heaters in Magnetic Nanoparticle
      Hyperthermia.
AB  - Magnetic vortices existing in soft magnetic nanoparticles with sizes larger than
      the single-domain diameter can be efficient nano-heaters in biomedical
      applications. Using micromagnetic numerical simulation we prove that in the
      optimal range of particle diameters the magnetization reversal of the vortices in
      spherical iron and magnetite nanoparticles is possible for moderate amplitudes of
      external alternating magnetic field, H0 < 100 Oe. In contrast to the case of
      superparamagnetic nanoparticles, for the vortex configuration the hysteresis loop
      area increases as a function of frequency. Therefore, high values of the specific
      absorption rate, on the order of 1000 W/g, can be obtained at frequencies f = 0.5
      1.0 MHz. Because the diameter D of a non single-domain particle is several times
      larger than the diameter d of a superparamagnetic particle, the volume of heat
      generation for the vortex turns out to be (D/d)3 times larger. This shows the
      advantage of vortex configurations for heat generation in alternating magnetic
      field in biomedical applications.

PMID- 29352176
TI  - Renal scattered tubular-like cells confer protective effects in the stenotic
      murine kidney mediated by release of extracellular vesicles.
AB  - To test the hypothesis that intrinsic renal scattered tubular cells (STC-like
      cells) contribute to repairing injured tubular epithelial cells (TEC) by
      releasing extracellular vesicle (EV). EV released from primary cultured pig STC
      like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced
      injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like
      cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury,
      oxidative stress and mitochondrial function were assessed. Transfer of
      mitochondria from STC-like cells to TEC was assessed using Mito-trackers, and
      their viability by mitochondrial membrane potential assays. STC-like cells
      derived EV were intra-arterially injected into mice 2 weeks after induction of
      unilateral renal artery stenosis. Two weeks later, renal hemodynamics were
      studied using magnetic-resonance-imaging, and renal fibrosis assessed ex-vivo.
      Cultured STC-like cells released EV that were uptaken by TEC. A protective effect
      conferred by STC-like cells in AMA-induced TEC injury was partly mimicked by
      their EV. Furthermore, STC-like cells-EV carried and transferred mitochondrial
      material to injured TEC, which partly restored mitochondrial function. In vivo,
      STC-like cells-derived EV engrafted in the stenotic kidney, and improved its
      perfusion and oxygenation. STC-like cells-EV exert protective effects on injured
      tubular cells in vitro and in vivo, partly by transferring STC-like cells
      mitochondria, which remain at least partly functional in recipient TEC.

PMID- 29352177
TI  - Photonic spin Hall effect enabled refractive index sensor using weak
      measurements.
AB  - In this work, we theoretically propose an optical biosensor (consists of a BK7
      glass, a metal film, and a graphene sheet) based on photonic spin Hall effect
      (SHE). We establish a quantitative relationship between the spin-dependent shift
      in photonic SHE and the refractive index of sensing medium. It is found that, by
      considering the surface plasmon resonance effect, the refractive index variations
      owing to the adsorption of biomolecules in sensing medium can effectively change
      the spin-dependent displacements. Remarkably, using the weak measurement method,
      this tiny spin-dependent shifts can be detected with a desirable accuracy so that
      the corresponding biomolecules concentration can be determined.

PMID- 29352178
TI  - Compositional Bias in Naive and Chemically-modified Phage-Displayed Libraries
      uncovered by Paired-end Deep Sequencing.
AB  - Understanding the composition of a genetically-encoded (GE) library is
      instrumental to the success of ligand discovery. In this manuscript, we
      investigate the bias in GE-libraries of linear, macrocyclic and chemically post
      translationally modified (cPTM) tetrapeptides displayed on the M13KE platform,
      which are produced via trinucleotide cassette synthesis (19 codons) and NNK
      randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector
      {L} (extension and ligation of synthetic DNA into the vector), naive libraries
      {N} (transformation of the ligated vector into the bacteria followed by
      expression of the library for 4.5 hours to yield a "naive" library), and
      libraries chemically modified by aldehyde ligation and cysteine macrocyclization
      {M} characterized by paired-end deep sequencing, detected a significant drop in
      diversity in {L} -> {N}, but only a minor compositional difference in {S} -> {L}
      and {N} -> {M}. Libraries expressed at the N-terminus of phage protein pIII
      censored positively charged amino acids Arg and Lys; libraries expressed between
      pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias
      towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde
      ligation and cysteine macrocyclization unveiled censorship of sequences with
      Ser/Phe. Analogous analysis can be used to explore library diversity in new
      display platforms and optimize cPTM of these libraries.

PMID- 29352179
TI  - Growth and remodeling play opposing roles during postnatal human heart valve
      development.
AB  - Tissue growth and remodeling are known to govern mechanical homeostasis in
      biological tissue, but their relative contributions to homeostasis remain
      unclear. Here, we use mechanical models, fueled by experimental findings, to
      demonstrate that growth and remodeling have different effects on heart valve
      stretch homeostasis during physiological postnatal development. Two developmental
      stages were considered: early-stage (from infant to adolescent) and late-stage
      (from adolescent to adult) development. Our models indicated that growth and
      remodeling play opposing roles in preserving tissue stretch and with time. During
      early-stage development, excessive tissue stretch was decreased by tissue growth
      and increased by remodeling. In contrast, during late-stage development tissue
      stretch was decreased by remodeling and increased by growth. Our findings
      contribute to an improved understanding of native heart valve adaptation
      throughout life, and are highly relevant for the development of tissue-engineered
      heart valves.

PMID- 29352180
TI  - Relationship between serum cortisol level and degree of false lumen thrombosis in
      patients with uncomplicated type B aortic dissection.
AB  - Partial thrombosis of the false lumen in uncomplicated type B aortic dissection
      (uTBAD) is associated with an increased late mortality risk. Whether the serum
      cortisol level can affect false lumen thrombosis in patients with uTBAD has not
      been well characterized. This study was performed on 87 patients with uTBAD. A
      curve-fitting method was used to analyze the relationship between serum cortisol
      and partial thrombosis of false lumen. Univariate and multivariate logistic
      regression analyses were used to identify false lumen partial thrombosis
      associated serum cortisol. Curve-fitting's result revealed a characteristic U
      shape, and 14.0 ug/dL was considered as the cutoff point for serum cortisol. The
      results of univariate and multivariate logistic regression analyses suggested
      that when trisecting the serum cortisol level into three parts, the low and high
      levels of serum cortisol could significantly affect the occurrence of false lumen
      partial thrombosis compared with the middle level. The odds ratio value of the
      low and high levels of serum cortisol was 6.12 and 4.65, respectively, in the
      univariate analysis, and 24.32 and 3.93, respectively, in the multivariate
      analysis. Low or high levels of serum cortisol might influence the natural result
      of uTBAD through affecting the false lumen thrombosis.

PMID- 29352181
TI  - SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia.
AB  - T-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median
      survival of the patients of less than two years. Besides characteristic
      chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT
      pathway members, and epigenetic regulators. We here performed a targeted mutation
      analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection
      of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations
      were identified in 30 of the 40 genes, 18 being recurrently mutated. We
      identified recurrently mutated genes previously unknown to be mutated in T-PLL,
      which are SAMHD1, HERC1, HERC2, PRDM2, PARP10, PTPRC, and FOXP1. SAMHD1 regulates
      cellular deoxynucleotide levels and acts as a potential tumor suppressor in other
      leukemias. We observed destructive mutations in 18% of cases as well as deletions
      in two further cases. Taken together, we identified additional genes involved in
      JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair
      (SAMHD1, PARP10, HERC1, and HERC2) as being recurrently mutated in T-PLL. Thus,
      our study considerably extends the picture of pathways involved in molecular
      pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with ~20%
      of T-PLL affected by destructive lesions likely as major player in T-PLL
      pathogenesis.

PMID- 29352182
TI  - Chloroplast genomic resources for phylogeny and DNA barcoding: a case study on
      Fritillaria.
AB  - The genus Fritillaria comprises approximately 130 perennial herbaceous species.
      In the Pharmacopoeia of the People's Republic of China, the bulbs of 11
      Fritillaria species are used in Chinese herbal medicines. However, the
      traditional methods of morphological classification cannot accurately identify
      closely related species of Fritillaria. Previous studies have attempted to
      identify these species with universal molecular markers, but insufficient
      phylogenetic signal was available. In this study, the complete chloroplast
      genomes of eight Fritillaria species were compared. The length of the eight
      Fritillaria chloroplast genomes ranges from 151,009 bp to 152,224 bp. A total of
      136 SSR loci were identified, including 124 polymorphic SSR loci. For large
      repeat sequences, 108 repeat loci and four types of repeats were observed. Ten
      highly variable regions were identified as potential molecular markers. These
      SSRs, large repeat sequences and highly variable regions provide important
      information for the development of genetic markers and DNA fingerprints.
      Phylogenetic analyses showed that the topological structures of all data sets
      (except the IR regions) were in complete agreement and well resolved. Overall,
      this study provides comprehensive chloroplast genomic resources, which will be
      valuable for future studies of evolution and species identification in
      Fritillaria.

PMID- 29352183
TI  - Environmental enrichment increases transcriptional and epigenetic differentiation
      between mouse dorsal and ventral dentate gyrus.
AB  - Early life experience influences stress reactivity and mental health through
      effects on cognitive-emotional functions that are, in part, linked to gene
      expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus
      (DG) is a major site for experience-dependent plasticity associated with
      sustained transcriptional alterations, potentially mediated by epigenetic
      modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and
      transcriptome data sets from mouse dorsal and ventral DG. We find genome-wide
      transcriptional and methylation differences between dorsal and ventral DG,
      including at key developmental transcriptional factors. Peripubertal
      environmental enrichment increases hippocampal volume and enhances dorsal DG
      specific differences in gene expression. Enrichment also enhances dorsal-ventral
      differences in DNA methylation, including at binding sites of the transcription
      factor NeuroD1, a regulator of adult neurogenesis. These results indicate a
      dorsal-ventral asymmetry in transcription and methylation that parallels well
      known functional and anatomical differences, and that may be enhanced by
      environmental enrichment.

PMID- 29352184
TI  - Expression and relevance of the G protein-gated K+ channel in the mouse
      ventricle.
AB  - The atrial G protein-gated inwardly rectifying K+ (GIRK) channel is a critical
      mediator of parasympathetic influence on cardiac physiology. Here, we probed the
      details and relevance of the GIRK channel in mouse ventricle. mRNAs for the
      atrial GIRK channel subunits (GIRK1, GIRK4), M2 muscarinic receptor (M2R), and
      RGS6, a negative regulator of atrial GIRK-dependent signaling, were detected in
      mouse ventricle at relatively low levels. The cholinergic agonist carbachol (CCh)
      activated small GIRK currents in adult wild-type ventricular myocytes that
      exhibited relatively slow kinetics and low CCh sensitivity; these currents were
      absent in ventricular myocytes from Girk1-/- or Girk4-/- mice. While loss of GIRK
      channels attenuated the CCh-induced shortening of action potential duration and
      suppression of ventricular myocyte excitability, selective ablation of GIRK
      channels in ventricle had no effect on heart rate, heart rate variability, or
      electrocardiogram parameters at baseline or after CCh injection. Additionally,
      loss of ventricular GIRK channels did not impact susceptibility to ventricular
      arrhythmias. These data suggest that the mouse ventricular GIRK channel is a
      GIRK1/GIRK4 heteromer, and show that while it contributes to the cholinergic
      suppression of ventricular myocyte excitability, this influence does not
      substantially impact cardiac physiology or ventricular arrhythmogenesis in the
      mouse.

PMID- 29352185
TI  - Genetic fingerprinting of salmon louse (Lepeophtheirus salmonis) populations in
      the North-East Atlantic using a random forest classification approach.
AB  - Caligid sea lice represent a significant threat to salmonid aquaculture
      worldwide. Population genetic analyses have consistently shown minimal population
      genetic structure in North Atlantic Lepeophtheirus salmonis, frustrating efforts
      to track louse populations and improve targeted control measures. The aim of this
      study was to test the power of reduced representation library sequencing (IIb-RAD
      sequencing) coupled with random forest machine learning algorithms to define
      markers for fine-scale discrimination of louse populations. We identified 1286
      robustly supported SNPs among four L. salmonis populations from Ireland, Scotland
      and Northern Norway. Only weak global structure was observed based on the full
      SNP dataset. The application of a random forest machine-learning algorithm
      identified 98 discriminatory SNPs that dramatically improved population
      assignment, increased global genetic structure and resulted in significant
      genetic population differentiation. A large proportion of SNPs found to be under
      directional selection were also identified to be highly discriminatory. Our data
      suggest that it is possible to discriminate between nearby L. salmonis
      populations given suitable marker selection approaches, and that such differences
      might have an adaptive basis. We discuss these data in light of sea lice adaption
      to anthropogenic and environmental pressures as well as novel approaches to track
      and predict sea louse dispersal.

PMID- 29352186
TI  - Glycolysis promotes caspase-3 activation in lipid rafts in T cells.
AB  - Resting T cells undergo a rapid metabolic shift to glycolysis upon activation in
      the presence of interleukin (IL)-2, in contrast to oxidative mitochondrial
      respiration with IL-15. Paralleling these different metabolic states are striking
      differences in susceptibility to restimulation-induced cell death (RICD);
      glycolytic effector T cells are highly sensitive to RICD, whereas non-glycolytic
      T cells are resistant. It is unclear whether the metabolic state of a T cell is
      linked to its susceptibility to RICD. Our findings reveal that IL-2-driven
      glycolysis promotes caspase-3 activity and increases sensitivity to RICD. Neither
      caspase-7, caspase-8, nor caspase-9 activity is affected by these metabolic
      differences. Inhibition of glycolysis with 2-deoxyglucose reduces caspase-3
      activity as well as sensitivity to RICD. By contrast, IL-15-driven oxidative
      phosphorylation actively inhibits caspase-3 activity through its
      glutathionylation. We further observe active caspase-3 in the lipid rafts of
      glycolytic but not non-glycolytic T cells, suggesting a proximity-induced model
      of self-activation. Finally, we observe that effector T cells during influenza
      infection manifest higher levels of active caspase-3 than naive T cells.
      Collectively, our findings demonstrate that glycolysis drives caspase-3 activity
      and susceptibility to cell death in effector T cells independently of upstream
      caspases. Linking metabolism, caspase-3 activity, and cell death provides an
      intrinsic mechanism for T cells to limit the duration of effector function.

PMID- 29352187
TI  - Reduction in hepatic secondary bile acids caused by short-term antibiotic-induced
      dysbiosis decreases mouse serum glucose and triglyceride levels.
AB  - Antibiotic-caused changes in intestinal flora (dysbiosis) can have various
      effects on the host. Secondary bile acids produced by intestinal bacteria are
      ligands for specific nuclear receptors, which regulate glucose, lipid, and drug
      metabolism in the liver. The present study aimed to clarify the effect of changes
      in secondary bile acids caused by antibiotic-induced dysbiosis on the host
      physiology, especially glucose, lipid, and drug metabolism. After oral
      administration of non-absorbable antibiotics for 5 days, decreased amounts of
      secondary bile acid-producing bacteria in faeces and a reduction in secondary
      bile acid [lithocholic acid (LCA) and deoxycholic acid (DCA)] levels in the liver
      were observed. Serum glucose and triglyceride levels were also decreased, and
      these decreases were reversed by LCA and DCA supplementation. Quantitative
      proteomics demonstrated that the expression levels of proteins involved in
      glycogen metabolism, cholesterol, bile acid biosynthesis, and drug metabolism
      (Cyp2b10, Cyp3a25, and Cyp51a1) were altered in the liver in dysbiosis, and these
      changes were reversed by LCA and DCA supplementation. These results suggested
      that secondary bile acid-producing bacteria contribute to the homeostasis of
      glucose and triglyceride levels and drug metabolism in the host, and have
      potential as therapeutic targets for treating metabolic disease.

PMID- 29352189
TI  - Mechanical behavior of a soft hydrogel reinforced with three-dimensional printed
      microfibre scaffolds.
AB  - Reinforcing hydrogels with micro-fibre scaffolds obtained by a Melt
      Electrospinning Writing (MEW) process has demonstrated great promise for
      developing tissue engineered (TE) constructs with mechanical properties
      compatible to native tissues. However, the mechanical performance and
      reinforcement mechanism of the micro-fibre reinforced hydrogels is not yet fully
      understood. In this study, FE models, implementing material properties measured
      experimentally, were used to explore the reinforcement mechanism of fibre
      hydrogel composites. First, a continuum FE model based on idealized scaffold
      geometry was used to capture reinforcement effects related to the suppression of
      lateral gel expansion by the scaffold, while a second micro-FE model based on
      micro-CT images of the real construct geometry during compaction captured the
      effects of load transfer through the scaffold interconnections. Results
      demonstrate that the reinforcement mechanism at higher scaffold volume fractions
      was dominated by the load carrying-ability of the fibre scaffold
      interconnections, which was much higher than expected based on testing scaffolds
      alone because the hydrogel provides resistance against buckling of the scaffold.
      We propose that the theoretical understanding presented in this work will assist
      the design of more effective composite constructs with potential applications in
      a wide range of TE conditions.

PMID- 29352188
TI  - Efficient scalable production of therapeutic microvesicles derived from human
      mesenchymal stem cells.
AB  - Microvesicles (MVs) released by cells are involved in a multitude of
      physiological events as important mediators of intercellular communication. MVs
      derived from mesenchymal stem cells (MSCs) contain various paracrine factors from
      the cells that primarily contribute to their therapeutic efficacy observed in
      numerous clinical trials. As nano-sized and bi-lipid layered vesicles retaining
      therapeutic potency equivalent to that of MSCs, MSC-derived MVs have been in
      focus as ideal medicinal candidates for regenerative medicine, and are preferred
      over MSC infusion therapy with their improved safety profiles. However, technical
      challenges in obtaining sufficient amounts of MVs have limited further progress
      in studies and clinical application. Of the multiple efforts to reinforce the
      therapeutic capacity of MSCs, few studies have reportedly examined the scale-up
      of MSC-derived MV production. In this study, we successfully amplified MV
      secretion from MSCs compared to the conventional culture method using a simple
      and efficient 3D-bioprocessing method. The MSC-derived MVs produced in our
      dynamic 3D-culture contained numerous therapeutic factors such as cytokines and
      micro-RNAs, and showed their therapeutic potency in in vitro efficacy evaluation.
      Our results may facilitate diverse applications of MSC-derived MVs from the bench
      to the bedside, which requires the large-scale production of MVs.

PMID- 29352190
TI  - Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via
      regulation of VEGF secretion.
AB  - Vascularization deficiency caused a lot of diseases, such as diabetes ulcer and
      myocardial infarction. Mesenchymal stem cells (MSCs), with the self-renewal and
      multipotent differentiation capacities, have been used for many diseases
      treatment through regulation microenvironment. Numerous studies reported that
      MSCs transplantation could largely improve cutaneous wound healing via paracrine
      secretion of growth factors. However, whether MSCs take part in the angiogenesis
      process directly remains elusive. Previous study proved that autophagy inhibited
      immunosuppressive function of MSCs and prevented the degradation of MSCs function
      in inflammatory and senescent microenvironment. Here, we proved that autophagy
      determines the therapeutic effect of MSCs in cutaneous wound healing through
      promoting endothelial cells angiogenesis and demonstrated that the paracrine of
      vascular endothelial growth factor (VEGF) in MSCs was required in wound site. We
      further revealed that autophagy enhanced the VEGF secretion from MSCs through ERK
      phosphorylation directly. Collectively, we put forward that autophagy mediated
      paracrine of VEGF plays a central role in MSCs cured cutaneous wound healing and
      may provide a new therapeutic method for angiogenesis-related diseases.

PMID- 29352191
TI  - Oral administration of Proteus mirabilis damages dopaminergic neurons and motor
      functions in mice.
AB  - Recently, studies on the relationship between gut dysbiosis and Parkinson's
      disease (PD) have increased, but whether a specific gut bacterium may cause PD
      remains unexplored. Here, we report, for the first time, that a specific gut
      bacterium directly induces PD symptoms and dopaminergic neuronal damage in the
      mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus
      mirabilis, markedly and commonly increased in PD mouse models. Administration of
      P. mirabilis isolated from PD mice significantly induced motor deficits,
      selectively caused dopaminergic neuronal damage and inflammation in substantia
      nigra and striatum, and stimulated alpha-synuclein aggregation in the brain as
      well as in the colon. We found that lipopolysaccharides, a virulence factor of P.
      mirabilis, may be associated in these pathological changes via gut leakage and
      inflammatory actions. Our results suggest a role of P. mirabilis on PD
      pathogenesis in the brain.

PMID- 29352192
TI  - Full-Wave Electromagnetic Optimisation of Corrugated Metallic Reectors Using a
      Multigrid Approach.
AB  - A multigrid optimisation strategy is introduced to design passive metallic
      reflectors with corrugated shapes. The strategy is based on using genetic
      algorithms at multiple grids and shaping the metal sheets, starting from coarse
      details to fine tunings. This corresponds to a systematic expansion of the
      related optimisation space, which is explored more efficiently in comparison to a
      brute-force optimisation without using grid. By employing the multilevel fast
      multipole algorithm to analyse the electromagnetic problems corresponding to
      optimisation trials, we obtain accurately designed reflectors that provide
      focussing abilities with very high performances at single and multiple locations.
      The designed reflectors are also resistant to fabrication errors with less
      complex corrugations and simplified reflection mechanisms compared to those found
      by no-grid optimisation trials.

PMID- 29352193
TI  - Degree of severity of molar incisor hypomineralization and its relation to dental
      caries.
AB  - Molar incisor hypomineralization is a developmental defect of dental enamel
      associated with rapid caries progression. In order to discover whether molar
      incisor hypomineralization predisposes to dental caries, a cross-sectional cohort
      study was conducted in a sample of 414 children aged between eight and nine
      years. It was found that 24.2% of the children presented molar incisor
      hypomineralization. Of these, 72% had a mild form and 28% a severe form. Caries
      prevalence was greater among the children with severe form (60.7%) than in those
      with mild form (43.1%) or no molar incisor hypomineralization (45.5%). The caries
      indices were higher in out molar incisor hypomineralization (1.18) or with mild
      form (1.08). The tooth-surface caries ratio was significantly higher in surfaces
      with severe hypomineralization than in those with no hypomineralization or mild
      hypomineralization. A linear regression model showed that cariogenic food intake
      and the presence of severe molar incisor hypomineralization were significantly
      associated with DMFS. Consequently, an association was found to exist between
      dental caries and the presence of surfaces affected by severe molar incisor
      hypomineralization, which should be considered a risk factor within the
      multifactorial etiology of caries.

PMID- 29352194
TI  - Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus
      cells by inducing autophagy in a model of intervertebral disc degeneration.
AB  - Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence
      and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6
      exerts potent anti-senescent and anti-apoptotic effects in models of age-related
      degenerative disease. However, it is not known whether sirt6 protects against
      IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced
      in senescent human NP cells. Sirt6 overexpression protected against apoptosis and
      both replicative and stress-induced premature senescence. Sirt6 also activated NP
      cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine
      (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and
      anti-apoptotic effects of sirt6, which regulated the expression of degeneration
      associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the
      data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by
      triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel
      therapeutic target for IDD treatment.

PMID- 29352196
TI  - Hyper-hippocampal glycogen induced by glycogen loading with exhaustive exercise.
AB  - Glycogen loading (GL), a well-known type of sports conditioning, in combination
      with exercise and a high carbohydrate diet (HCD) for 1 week enhances individual
      endurance capacity through muscle glycogen supercompensation. This exercise-diet
      combination is necessary for successful GL. Glycogen in the brain contributes to
      hippocampus-related memory functions and endurance capacity. Although the effect
      of HCD on the brain remains unknown, brain supercompensation occurs following
      exhaustive exercise (EE), a component of GL. We thus employed a rat model of GL
      and examined whether GL increases glycogen levels in the brain as well as in
      muscle, and found that GL increased glycogen levels in the hippocampus and
      hypothalamus, as well as in muscle. We further explored the essential components
      of GL (exercise and/or diet conditions) to establish a minimal model of GL
      focusing on the brain. Exercise, rather than a HCD, was found to be crucial for
      GL-induced hyper-glycogen in muscle, the hippocampus and the hypothalamus.
      Moreover, EE was essential for hyper-glycogen only in the hippocampus even
      without HCD. Here we propose the EE component of GL without HCD as a condition
      that enhances brain glycogen stores especially in the hippocampus, implicating a
      physiological strategy to enhance hippocampal functions.

PMID- 29352195
TI  - Association between modified CHA2DS2-VASc Score with Ankle-Brachial index < 0.9.
AB  - The ankle-brachial index (ABI) is a reliable diagnostic examination for
      peripheral arterial occlusive disease (PAOD). We previously reported CHADS2 score
      was significantly correlated with PAOD. However, the association between CHA2DS2
      VASc score and ABI < 0.9 is not evaluated in the literature. The aim of the
      present study was to investigate whether CHA2DS2-VASc score has a strong
      association with PAOD. We enrolled 1482 patients in this study. PAOD was defined
      as ABI < 0.9 in either leg. Vascular disease in CHA2DS2-VASc score was modified
      as vascular disease except PAOD. Of the 1482 subjects, the prevalence of ABI <
      0.9 was 5.6%. Multivariate analysis showed that the increased age, decreased
      estimated glomerular filtration rate and increased modified CHA2DS2-VASc score
      (OR, 1.764; p < 0.001) were independent associated with ABI < 0.9. In addition,
      the percentage of ABI < 0.9 in patients with modified CHA2DS2-VASc score of 0, 1,
      and <2 were 0%, 0.9%, and 0.7%, respectively (All < 1%). Our study demonstrated
      modified CHA2DS2-VASc score was significantly associated with ABI < 0.9.
      Calculation of modified CHA2DS2-VASc score might be useful in identifying
      patients with PAOD and in stratifying the risk of PAOD in non-AF patients.

PMID- 29352197
TI  - Phylogenetic and Functional Structure of Wintering Waterbird Communities
      Associated with Ecological Differences.
AB  - Ecological differences may be related to community component divisions between
      Oriental (west) and Sino-Japanese (east) realms, and such differences may result
      in weak geographical breaks in migratory species that are highly mobile. Here, we
      conducted comparative phylogenetic and functional structure analyses of wintering
      waterbird communities in southern China across two realms and subsequently
      examined possible climate drivers of the observed patterns. An analysis based on
      such highly migratory species is particularly telling because migration is bound
      to reduce or completely eliminate any divergence between communities.
      Phylogenetic and functional structure of eastern communities showed over
      dispersion while western communities were clustered. Basal phylogenetic and
      functional turnover of western communities was significant lower than that of
      eastern communities. The break between eastern and western communities was masked
      by these two realms. Geographic patterns were related to mean temperature changes
      and temperature fluctuations, suggesting that temperature may filter waterbird
      lineages and traits, thus underlying geographical community divisions. These
      results suggest phylogenetic and functional divisions in southern China,
      coinciding with biogeography. This study shows that temperature fluctuations
      constitute an essential mechanism shaping geographical divisions that have
      largely gone undetected previously, even under climate change.

PMID- 29352198
TI  - oriD structure controls RepD initiation during rolling-circle replication.
AB  - Bacterial antibiotic resistance is often carried by circular DNA plasmids that
      are copied separately from the genomic DNA and can be passed to other bacteria,
      spreading the resistance. The chloramphenicol-resistance plasmid pC221 from
      Staphylococcus aureus is duplicated by a process called asymmetric rolling circle
      replication. It is not fully understood how the replication process is regulated
      but its initiation requires a plasmid-encoded protein called RepD that nicks one
      strand of the parent plasmid at the double-stranded origin of replication (oriD).
      Using magnetic tweezers to control the DNA linking number we found RepD nicking
      occurred only when DNA was negatively supercoiled and that binding of a non
      nicking mutant (RepDY188F) stabilized secondary structure formation at oriD.
      Quenched-flow experiments showed the inverted complementary repeat sequence,
      ICRII, within oriD was most important for rapid nicking of intact plasmids. Our
      results show that cruciform formation at oriD is an important control for
      initiation of plasmid replication.

PMID- 29352199
TI  - Prevention of Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome.
AB  - Smith-Lemli-Opitz Syndrome (SLOS) is a recessive human disease caused by
      defective cholesterol (CHOL) synthesis at the level of DHCR7 (7
      dehydrocholesterol reductase), which normally catalyzes the conversion of 7
      dehydrocholesterol (7DHC) to CHOL. Formation and abnormal accumulation of 7DHC
      and 7DHC-derived oxysterols occur in SLOS patients and in rats treated with the
      DHCR7 inhibitor AY9944. The rat SLOS model exhibits progressive and irreversible
      retinal dysfunction and degeneration, which is only partially ameliorated by
      dietary CHOL supplementation. We hypothesized that 7DHC-derived oxysterols are
      causally involved in this retinal degeneration, and that blocking or reducing
      their formation should minimize the phenotype. Here, using the SLOS rat model, we
      demonstrate that combined dietary supplementation with CHOL plus antioxidants
      (vitamins E and C, plus sodium selenite) provides better outcomes than dietary
      CHOL supplementation alone with regard to preservation of retinal structure and
      function and lowering 7DHC-derived oxysterol formation. These proof-of-principle
      findings provide a translational, pre-clinical framework for designing clinical
      trials using CHOL-antioxidant combination therapy as an improved therapeutic
      intervention over the current standard of care for the treatment of SLOS.

PMID- 29352200
TI  - Meta-analysis of soil mercury accumulation by vegetables.
AB  - Mercury pollution in soil poses serious risks to human health through consumption
      of contaminated vegetables. We used a meta-analysis to examine the mercury
      enrichment ability of different vegetables and the main factors affecting mercury
      uptake. We drew the following conclusions. (1) Plants with a lower
      bioconcentration factor (BCF) include cowpea, long bean, and radish, whereas
      plants with a higher BCF include green pepper, spinach, cabbage, and Chinese
      cabbage. (2) Leaf and cucurbit have the highest and lowest capacity,
      respectively, for mercury enrichment. (3) When soil pH is <6.5, mercury level
      uptake by the plant increases, whereas it decreases when the pH is >7.5, meaning
      that increased soil pH reduces mercury uptake in soil. (4) When soil organic
      matter (SOM) is lower than 20 g/kg, tuber plants have the highest and eggplant
      has the lowest mercury adsorption capacity, respectively. When SOM is 20-30 g/kg,
      cucurbit has the lowest and leaf the highest adsorption capacity, respectively.
      When SOM is higher than 30 g/kg, however, eggplant has the highest mercury
      adsorption capacity, but there were no significant differences among the five
      types of vegetables. We argue that this meta-analysis aids in selecting
      vegetables suitable for absorption of heavy metals from polluted soil.

PMID- 29352202
TI  - Publisher Correction: Correction of a Disease Mutation using CRISPR/Cas9-assisted
      Genome Editing in Japanese Black Cattle.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29352203
TI  - Advanced Modified Polyacrylonitrile Membrane with Enhanced Adsorption Property
      for Heavy Metal Ions.
AB  - Advanced modified polyacrylonitrile (PAN) membrane with high adsorption property
      for heavy metal ions was designed and fabricated for the first time. The
      introduced diazoresin-ethylenediaminetetraacetic acid (DR-EDTA) layer could
      effectively absorb the metal ion, such as Cu2+, Pb2+, Hg2+ in the waste water.
      The effects of layers, metal ion concentration, pH, temperature and cycle time
      were investigated. The results showed that the adsorption isotherms for Cu2+ were
      well fitted by Langmuir model. The maximum adsorption capacity of the modified
      membrane for Cu2+ was approximately 47.6 mg/g. In addition, the prepared PAN-(DR
      EDTA)3 membrane could be regenerated more than 720 h based on their
      adsorption/desorption cycles. The results demonstrated that the modified PAN
      membrane could be used as effective adsorbents for heavy metal removal from waste
      water.

PMID- 29352201
TI  - Cross-species transcriptional analysis reveals conserved and host-specific
      neoplastic processes in mammalian glioma.
AB  - Glioma is a unique neoplastic disease that develops exclusively in the central
      nervous system (CNS) and rarely metastasizes to other tissues. This feature
      strongly implicates the tumor-host CNS microenvironment in gliomagenesis and
      tumor progression. We investigated the differences and similarities in glioma
      biology as conveyed by transcriptomic patterns across four mammalian hosts: rats,
      mice, dogs, and humans. Given the inherent intra-tumoral molecular heterogeneity
      of human glioma, we focused this study on tumors with upregulation of the
      platelet-derived growth factor signaling axis, a common and early alteration in
      human gliomagenesis. The results reveal core neoplastic alterations in mammalian
      glioma, as well as unique contributions of the tumor host to neoplastic
      processes. Notable differences were observed in gene expression patterns as well
      as related biological pathways and cell populations known to mediate key elements
      of glioma biology, including angiogenesis, immune evasion, and brain invasion.
      These data provide new insights regarding mammalian models of human glioma, and
      how these insights and models relate to our current understanding of the human
      disease.

PMID- 29352204
TI  - Local structure, nucleation sites and crystallization behavior and their effects
      on magnetic properties of Fe81Si x B10P8-xCu1 (x = 0~8).
AB  - In this work, an attempt has been made to reveal critical factors dominating the
      crystallization and soft magnetic properties of Fe81Si x B10P8-xCu1 (x = 0, 2, 4,
      6 and 8) alloys. Both melt spun and annealed alloys are characterized by
      differential scanning calorimetry, X-ray diffractometry, Mossbauer spectroscopy,
      transmission electron microscopy, positron annihilation lifetime spectroscopy and
      magnetometry. The changes in magnetic interaction between Fe atoms and chemical
      homogeneity can well explain the variation of magnetic properties of Fe81Si x
      B10P8-xCu1 amorphous alloys. The density of nucleation sites in the amorphous
      precursors decreases in the substitution of P by Si. Meanwhile, the precipitated
      nanograins gradually coarsen, but the inhibiting effect of P on grain growth
      diminishes causing the increase of the crystallinity. Moreover, various site
      occupancies of Si are observed in the nanocrystallites and the Si occupancy in
      bcc Fe decreases the average magnetic moment of nanograins. Without sacrificing
      amorphous forming ability, we can obtain FeSiBPCu nanocrystalline alloy with
      excellent soft magnetic properties by optimizing the content of Si and P in the
      amorphous precursors.

PMID- 29352205
TI  - 2,5-Hexanedione induces dopaminergic neurodegeneration through integrin
      alphaMbeta2/NADPH oxidase axis-mediated microglial activation.
AB  - Recent study demonstrated that chronic exposure to solvents increases the risk of
      Parkinson's disease (PD), the second most common neurodegenerative disorder
      characterized by progressive dopaminergic neurodegeneration in the substantia
      nigra (SN). n-Hexane, a widely used organic solvent, displays central-peripheral
      neurotoxicity, which is mainly mediated by its active metabolite, 2,5-hexanedione
      (HD). However, whether HD exposure contributes to PD remains unclear. In this
      study, we found that rats exposed to HD displayed progressive dopaminergic
      neurodegeneration in the nigrostriatal system. Microglial activation was also
      detected in HD-treated rats, which occurred prior to degeneration of dopaminergic
      neurons. Moreover, depletion of microglia markedly reduced HD-induced
      dopaminergic neurotoxicity. Mechanistic study revealed an essential role of
      microglial integrin alphaMbeta2-NADPH oxidase (NOX2) axis in HD-elicited
      neurotoxicity. HD activated NOX2 by inducing membrane translocation of NOX2
      cytosolic subunit, p47phox. Integrin alphaMbeta2 was critical for HD-induced NOX2
      activation since inhibition or genetic deletion of alphaMbeta2 attenuated NOX2
      generated superoxide and p47phox membrane translocation in response to HD. Src
      and Erk, two downstream signals of alphaMbeta2, were recognized to bridge
      HD/alphaMbeta2-mediated NOX2 activation. Finally, pharmacological inhibition of
      alphaMbeta2-NOX2 axis attenuated HD-induced microglial activation and
      dopaminergic neurodegeneration. Our findings revealed that HD exposure damaged
      nigrostriatal dopaminergic system through alphaMbeta2-NOX2 axis-mediated
      microglial activation, providing, for the first time, experimental evidence for n
      hexane exposure contributing to the etiology of PD.

PMID- 29352206
TI  - Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models
      of crystal-mediated inflammation.
AB  - This study assesses the efficacy and exposure-response relationship of omega-3
      carboxylic acids (OM-3 CA) in models of crystal-based inflammation. Human THP-1
      macrophages and primary peripheral blood mononuclear cells exposed to multiple
      inflammatory crystal types were used to determine the anti-inflammatory potential
      of omega-3 (OM-3) fatty acids in vitro. Anti-inflammatory effects of OM-3 CA in
      vivo were tested in rat monosodium urate (MSU) crystal air pouch and rat knee
      intra-articular MSU injection models. Acute treatment with the OM-3 fatty acid
      docosahexaenoic acid suppressed MSU-, cholesterol crystal-, and calcium
      pyrophosphate crystal-mediated interleukin-1beta (IL-1beta) production in vitro.
      In vivo, OM-3 CA dose-dependently reduced crystal-mediated cell migration,
      exudate volume, and levels of IL-1beta and prostaglandin E2. Following intra
      articular injection of MSU, treatment with OM-3-CA (1 mL/kg) and indomethacin (1
      mg/kg) resulted in similar mean reductions in pain (23% and 41%, respectively)
      and swelling (58% and 50%, respectively), compared with controls. Additionally,
      in complex formulations of OM-3 fatty acids, high levels of palmitic acid could
      reduce the in vivo effect on crystal-mediated IL-1beta elevation. OM-3 CA has a
      broadly efficacious anti-inflammatory effect with a strong exposure-response
      relationship that could be beneficial in prevention and treatment of crystal
      arthritis, with potential applications in other IL-1beta-mediated diseases.

PMID- 29352207
TI  - Ethanol sensitizes hepatocytes for TGF-beta-triggered apoptosis.
AB  - : Alcohol abuse is a global health problem causing a substantial fraction of
      chronic liver diseases. Abundant TGF-beta-a potent pro-fibrogenic cytokine-leads
      to disease progression. Our aim was to elucidate the crosstalk of TGF-beta and
      alcohol on hepatocytes. Primary murine hepatocytes were challenged with ethanol
      and TGF-beta and cell fate was determined. Fluidigm RNA analyses revealed
      transcriptional effects that regulate survival and apoptosis. Mechanistic
      insights were derived from enzyme/pathway inhibition experiments and modulation
      of oxidative stress levels. To substantiate findings, animal model specimens and
      human liver tissue cultures were investigated. RESULTS: On its own, ethanol had
      no effect on hepatocyte apoptosis, whereas TGF-beta increased cell death.
      Combined treatment led to massive hepatocyte apoptosis, which could also be
      recapitulated in human HCC liver tissue treated ex vivo. Alcohol boosted the TGF
      beta pro-apoptotic gene signature. The underlying mechanism of pathway crosstalk
      involves SMAD and non-SMAD/AKT signaling. Blunting CYP2E1 and ADH activities did
      not prevent this effect, implying that it was not a consequence of alcohol
      metabolism. In line with this, the ethanol metabolite acetaldehyde did not mimic
      the effect and glutathione supplementation did not prevent the super-induction of
      cell death. In contrast, blocking GSK-3beta activity, a downstream mediator of
      AKT signaling, rescued the strong apoptotic response triggered by ethanol and TGF
      beta. This study provides novel information on the crosstalk between ethanol and
      TGF-beta. We give evidence that ethanol directly leads to a boost of TGF-beta's
      pro-apoptotic function in hepatocytes, which may have implications for patients
      with chronic alcoholic liver disease.

PMID- 29352208
TI  - Abnormal Speech Motor Control in Individuals with 16p11.2 Deletions.
AB  - Speech and motor deficits are highly prevalent (>70%) in individuals with the 600
      kb BP4-BP5 16p11.2 deletion; however, the mechanisms that drive these deficits
      are unclear, limiting our ability to target interventions and advance treatment.
      This study examined fundamental aspects of speech motor control in participants
      with the 16p11.2 deletion. To assess capacity for control of voice, we examined
      how accurately and quickly subjects changed the pitch of their voice within a
      trial to correct for a transient perturbation of the pitch of their auditory
      feedback. When compared to controls, 16p11.2 deletion carriers show an over
      exaggerated pitch compensation response to unpredictable mid-vocalization pitch
      perturbations. We also examined sensorimotor adaptation of speech by assessing
      how subjects learned to adapt their sustained productions of formants (speech
      spectral peak frequencies important for vowel identity), in response to
      consistent changes in their auditory feedback during vowel production. Deletion
      carriers show reduced sensorimotor adaptation to sustained vowel identity changes
      in auditory feedback. These results together suggest that 16p11.2 deletion
      carriers have fundamental impairments in the basic mechanisms of speech motor
      control and these impairments may partially explain the deficits in speech and
      language in these individuals.

PMID- 29352209
TI  - Evaluating street view exposure measures of visible green space for health
      research.
AB  - Urban green space, or natural environments, are associated with multiple physical
      and mental health outcomes. Several proposed pathways of action for these
      benefits (e.g., stress reduction and attention restoration) require visual
      perception of green space; however, existing green space exposure measures
      commonly used in epidemiological studies do not capture street-scale exposures.
      We downloaded 254 Google Street View (GSV) panorama images from Portland, Oregon
      and calculated percent of green in each image, called Green View Index (GVI). For
      these locations we also calculated satellite-based normalized difference
      vegetation index (NDVI), % tree cover, % green space, % street tree buffering,
      distance to parks, and several neighborhood socio-economic variables.
      Correlations between the GVI and other green space measures were low (-0.02 to
      0.50), suggesting GSV-based measures captured unique information about green
      space exposures. We further developed a GVI:NDVI ratio, which was associated with
      the amount of vertical green space in an image. The GVI and GVI:NDVI ratio were
      weakly related to neighborhood socioeconomic status and are therefore less
      susceptible to confounding in health studies compared to other green space
      measures. GSV measures captured unique characteristics of the green space
      environment and offer a new approach to examine green space and health
      associations in epidemiological research.

PMID- 29352210
TI  - Distribution and the origin of invasive apple snails, Pomacea canaliculata and P.
      maculata (Gastropoda: Ampullariidae) in China.
AB  - Species of Pomacea, commonly known as apple snails, are native to South America,
      and have become widely distributed agricultural and environmental pests in
      southern China since their introduction in the 1980s. However, only since 2010
      have researchers recognized that at least two species, P. canaliculata and P.
      maculata, are present in China. Although impacts of apple snails have been
      extensively documented, confusion still persists regarding current distributions
      and origin of the species in China. To resolve this confusion, we used
      phylogenetic and phylogeographic methods to analyze 1464 mitochondrial COI
      sequences, including 349 new sequences from samples collected in southern China
      and 1115 publicly available sequences from snails collected in the native and
      introduced ranges. Pomacea canaliculata was found at all sampled localities,
      while P. maculata was found at only five sampled localities in the Sichuan basin
      and Zhejiang province. Our data indicate that Chinese populations of P.
      canaliculata share an Argentinian origin, consistent with multiple introductions
      of this species elsewhere in Asia. In addition, just a single lineage of P.
      maculata is established in China, which shares with populations in Brazil.

PMID- 29352212
TI  - Rare mutations in apoptosis related genes APAF1, CASP9, and CASP3 contribute to
      human neural tube defects.

PMID- 29352211
TI  - HDL nanoparticles targeting sonic hedgehog subtype medulloblastoma.
AB  - Medulloblastoma is the most common paediatric malignant brain cancer and there is
      a need for new targeted therapeutic approaches to more effectively treat these
      malignant tumours, which can be divided into four molecular subtypes. Here, we
      focus on targeting sonic hedgehog (SHH) subtype medulloblastoma, which accounts
      for approximately 25% of all cases. The SHH subtype relies upon cholesterol
      signalling for tumour growth and maintenance of tumour-initiating cancer stem
      cells (CSCs). To target cholesterol signalling, we employed biomimetic high
      density lipoprotein nanoparticles (HDL NPs) which bind to the HDL receptor,
      scavenger receptor type B-1 (SCARB1), depriving cells of natural HDL and their
      cholesterol cargo. We demonstrate uptake of HDL NPs in SCARB1 expressing
      medulloblastoma cells and depletion of cholesterol levels in cancer cells. HDL
      NPs potently blocked proliferation of medulloblastoma cells, as well as hedgehog
      driven Ewing sarcoma cells. Furthermore, HDL NPs disrupted colony formation in
      medulloblastoma and depleted CSC populations in medulloblastoma and Ewing
      sarcoma. Altogether, our findings provide proof of principle for the development
      of a novel targeted approach for the treatment of medulloblastoma using HDL NPs.
      These findings present HDL-mimetic nanoparticles as a promising therapy for sonic
      hedgehog (SHH) subtype medulloblastoma and possibly other hedgehog-driven
      cancers.

PMID- 29352214
TI  - Handheld magnetic probe with permanent magnet and Hall sensor for identifying
      sentinel lymph nodes in breast cancer patients.
AB  - The newly developed radioisotope-free technique based on magnetic nanoparticle
      detection using a magnetic probe is a promising method for sentinel lymph node
      biopsy. In this study, a novel handheld magnetic probe with a permanent magnet
      and magnetic sensor is developed to detect the sentinel lymph nodes in breast
      cancer patients. An outstanding feature of the probe is the precise positioning
      of the sensor at the magnetic null point of the magnet, leading to highly
      sensitive measurements unaffected by the strong ambient magnetic fields of the
      magnet. Numerical and experimental results show that the longitudinal detection
      length is approximately 10 mm, for 140 MUg of iron. Clinical tests were
      performed, for the first time, using magnetic and blue dye tracers-without
      radioisotopes-in breast cancer patients to demonstrate the performance of the
      probe. The nodes were identified through transcutaneous and ex-vivo measurements,
      and the iron accumulation in the nodes was quantitatively revealed. These results
      show that the handheld magnetic probe is useful in sentinel lymph node biopsy and
      that magnetic techniques are widely being accepted as future standard methods in
      medical institutions lacking nuclear medicine facilities.

PMID- 29352213
TI  - Cucumber mosaic virus coat protein induces the development of chlorotic symptoms
      through interacting with the chloroplast ferredoxin I protein.
AB  - Cucumber mosaic virus (CMV) infection could induce mosaic symptoms on a wide
      range of host plants. However, there is still limited information regarding the
      molecular mechanism underlying the development of the symptoms. In this study,
      the coat protein (CP) was confirmed as the symptom determinant by exchanging the
      CP between a chlorosis inducing CMV-M strain and a green-mosaic inducing CMV-Q
      strain. A yeast two-hybrid analysis and bimolecular fluorescence complementation
      revealed that the chloroplast ferredoxin I (Fd I) protein interacted with the CP
      of CMV-M both in vitro and in vivo, but not with the CP of CMV-Q. The severity of
      chlorosis was directly related to the expression of Fd1, that was down-regulated
      in CMV-M but not in CMV-Q. Moreover, the silencing of Fd I induced chlorosis
      symptoms that were similar to those elicited by CMV-M. Subsequent analyses
      indicated that the CP of CMV-M interacted with the precursor of Fd I in the
      cytoplasm and disrupted the transport of Fd I into chloroplasts, leading to the
      suppression of Fd I functions during a viral infection. Collectively, our
      findings accentuate that the interaction between the CP of CMV and Fd I is the
      primary determinant for the induction of chlorosis in tobacco.

PMID- 29352215
TI  - Magnetically sensitive nanodiamond-doped tellurite glass fibers.
AB  - Traditional optical fibers are insensitive to magnetic fields, however many
      applications would benefit from fiber-based magnetometry devices. In this work,
      we demonstrate a magnetically sensitive optical fiber by doping nanodiamonds
      containing nitrogen vacancy centers into tellurite glass fibers. The fabrication
      process provides a robust and isolated sensing platform as the magnetic sensors
      are fixed in the tellurite glass matrix. Using optically detected magnetic
      resonance from the doped nanodiamonds, we demonstrate detection of local magnetic
      fields via side excitation and longitudinal collection. This is a first step
      towards intrinsically magneto-sensitive fiber devices with future applications in
      medical magneto-endoscopy and remote mineral exploration sensing.

PMID- 29352216
TI  - Black-legged kittiwakes as messengers of Atlantification in the Arctic.
AB  - Climate warming is rapidly altering marine ecosystems towards a more temperate
      state on the European side of the Arctic. However, this "Atlantification" has
      rarely been confirmed, as long-term datasets on Arctic marine organisms are
      scarce. We present a 19-year time series (1982-2016) of diet samples from black
      legged kittiwakes as an indicator of the changes in a high Arctic marine
      ecosystem (Kongsfjorden, Svalbard). Our results highlight a shift from Arctic
      prey dominance until 2006 to a more mixed diet with high contribution of Atlantic
      fishes. Capelin, an Atlantic species, dominated the diet composition in 2007,
      marking a shift in the food web. The occurrence of polar cod, a key Arctic fish
      species, positively correlated with sea ice index, whereas Atlantic species
      demonstrated the opposite correlation indicating that the diet shift was likely
      connected with recent climate warming. Kittiwakes, which gather available fish
      and zooplankton near the sea surface to feed their chicks, can act as messengers
      of ecosystem change. Changes in their diet reveal that the Kongsfjord system has
      drifted in an Atlantic direction over the last decade.

PMID- 29352217
TI  - Bedside assessment of regional cerebral perfusion using near-infrared
      spectroscopy and indocyanine green in patients with atherosclerotic occlusive
      disease.
AB  - This pilot study aimed to investigate the utility of near-infrared
      spectroscopy/indocyanine green (NIRS/ICG) for examining patients with occlusive
      cerebrovascular disease. Twenty-nine patients with chronic-stage atherosclerotic
      occlusive cerebrovascular disease were included. The patients were monitored
      using NIRS at the bedside. Using ICG time-intensity curves, the affected-to
      unaffected side ratios were calculated for several parameters, including the
      maximum ICG concentration (DeltaICGmax), time to peak (TTP), rise time (RT), and
      blood flow index (BFI = DeltaICGmax/RT), and were compared to the affected-to
      unaffected side ratios of the regional cerebral blood flow (rCBF) and regional
      oxygen extraction fraction (rOEF) obtained using positron emission tomography
      with 15O-labeled gas. The BFI ratio showed the best correlation with the rCBF
      ratio among these parameters (r = 0.618; P = 0.0004), and the RT ratio showed the
      best correlation with the rOEF ratio (r = 0.593; P = 0.0007). The patients were
      further divided into reduced rCBF or elevated rOEF groups, and the analysis
      revealed significant related differences. The present results advance the
      measurement of ICG kinetics using NIRS as a useful tool for the detection of
      severely impaired perfusion with reduced rCBF or elevated rOEF. This method may
      be applicable as a monitoring tool for patients with acute ischemic stroke.

PMID- 29352218
TI  - Nutritional deficiencies and bone metabolism after endobarrier in obese type 2
      patients with diabetes.
AB  - Endobarrier(r) is a minimally invasive, reversible endoscopic treatment for
      obesity. It provokes malabsorption along 60 cm of the small intestine, which can
      contribute to the development of vitamin deficiencies and to changes in bone
      mineral density (BMD). To determine the prevalence of nutrient deficiencies,
      changes in body composition and BMD during the first year after Endobarrier(r)
      placement. Twenty-one patients with type 2 diabetes met inclusion criteria.
      Levels of vitamins, micro and macronutrients were assessed prior and at 1, 3 and
      12 months post-operatively. DEXA was performed before and 12 months after
      implant. Nineteen patients completed the 12 months follow-up. Vitamin D
      deficiency was the most prevalent finding before Endobarrier(r) implant. The
      percentage of patients with severe deficiency decreased from 19 to 5% at 12
      months after supplementation. Microcytic anaemia was initially present in 9.5% of
      patients and increased to 26.3% at 12 months. Low ferritin and vitamin B12 levels
      were observed in 14.2 and 4.8% of patients before the implant and worsened to 42
      and 10.5%. Low concentrations of magnesium and phosphorus were also common but
      improved along the study. A significant but not clinically relevant decrease in
      BMD of 4.14 +/- 4.0% at the femoral neck was observed at 12 months without
      changes in osteocalcin levels. Vitamin deficiencies are common after
      Endobarrier(r) implant. It is therefore important to screen patients prior to and
      at regular intervals after the implant, and to encourage adherence to diet
      counselling and supplementation.

PMID- 29352219
TI  - New alkylresorcinol metabolites in spot urine as biomarkers of whole grain wheat
      and rye intake in a Swedish middle-aged population.
AB  - BACKGROUND/OBJECTIVES: Studies on the health effects of whole grains typically
      use self-reported intakes which are prone to large measurement errors. Dietary
      biomarkers that can provide an objective measure of intake are needed. New
      alkylresorcinol (AR) metabolites (3,5-dihydroxycinnamic acid (DHCA), 2-(3,5
      dihydroxybenzamido)acetic acid (DHBA-glycine) and 5-(3,5-dihydroxyphenyl)
      pentanoic acid (DHPPTA)) in 24 h urine samples have been suggested as biomarkers
      for whole grain (WG) wheat and rye intake but remain to be evaluated in spot
      urine samples. SUBJECTS/METHODS: The reproducibility of the new AR metabolites
      (DHCA, DHBA-glycine and DHPPTA) was investigated in 4 repeated samples over a
      period of 2 wk in spot urine from 40 Swedish men and women enroled in the SCAPIS
      study, after adjustment of creatinine. Metabolite concentrations were correlated
      with total whole grain intake estimated during the same period. RESULTS: The
      medium-term reproducibility determined for DHCA, DHPPTA and DHBA-glycine varied
      from moderate to excellent (intra-class correlation coefficient = 0.35-0.67).
      Moreover, DHCA and DHBA-glycine were independently associated with self-reported
      total WG intake (beta = 0.18, P = 0.08 and beta = 0.18, P = 0.02, respectively)
      and all metabolites except for DHPPA were higher among women. CONCLUSIONS: This
      study supports the idea of using AR metabolites in one or several spot urine
      samples as biomarkers of whole grain intake. These findings need to be confirmed
      in different populations.

PMID- 29352220
TI  - SOCE induced calcium overload regulates autophagy in acute pancreatitis via
      calcineurin activation.
AB  - Acute pancreatitis (AP) is an acute inflammatory process of the pancreas that is
      characterized by inflammation, edema, vacuolization and necrosis, which has
      significant morbidity and lethality. The pathogenesis of AP has not been
      established completely. An early and critical feature of AP is the aberrant
      signaling of Calcium (Ca2+) within the pancreatic acinar cell, termed Ca2+
      overload. Store-operated Ca2+ (SOC) channels are the principal Ca2+ influx
      channels that contribute to Ca2+ overload in pancreatic acinar cells. Store
      operated Ca2+ entry (SOCE) has been proved to be a key pathogenic step in AP
      development that leads to trypsin activation, inflammation and vacuolization.
      However, the molecular mechanisms are still poorly understood. By establishing
      Ca2+ overload model and mouse AP model using caerulein, we found that caerulein
      triggered SOCE via inducing interaction between STIM1 and Orai1, which activated
      calcineurin (CaN); CaN activated the nuclear factor of activated T cells (NFAT)
      and transcription factor EB (TFEB), thus promoting the transcriptional activation
      of multiple chemokines genes and autophagy-associated genes respectively. To the
      best of our knowledge, this is the first evidence showing that SOCE activates
      TFEB via CaN activation, which may have noticeable longer-term effects on
      autophagy and vacuolization in AP development. Our findings reveal the role for
      SOCE/CaN in AP development and provide potential targets for AP treatment.

PMID- 29352221
TI  - Role of METTL20 in regulating beta-oxidation and heat production in mice under
      fasting or ketogenic conditions.
AB  - METTL20 is a seven-beta-strand methyltransferase that is localised to the
      mitochondria and tri-methylates the electron transfer flavoprotein (ETF) beta
      subunit (ETFB) at lysines 200 and 203. It has been shown that METTL20 decreases
      the ability of ETF to extract electrons from medium-chain acyl-coenzyme A (CoA)
      dehydrogenase (MCAD) and glutaryl-CoA dehydrogenase in vitro. METTL20-mediated
      methylation of ETFB influences the oxygen consumption rate in permeabilised
      mitochondria, suggesting that METTL20-mediated ETFB methylation may also play a
      regulatory role in mitochondrial metabolism. In this study, we generated Mettl20
      knockout (KO) mice to uncover the in vivo functions of METTL20. The KO mice were
      viable, and a loss of ETFB methylation was confirmed. In vitro enzymatic assays
      revealed that mitochondrial ETF activity was higher in the KO mice than in wild
      type mice, suggesting that the KO mice had higher beta-oxidation capacity.
      Calorimetric analysis showed that the KO mice fed a ketogenic diet had higher
      oxygen consumption and heat production. A subsequent cold tolerance test
      conducted after 24 h of fasting indicated that the KO mice had a better ability
      to maintain their body temperature in cold environments. Thus, METTL20 regulates
      ETF activity and heat production through lysine methylation when beta-oxidation
      is highly activated.

PMID- 29352222
TI  - Artificial chameleon skin that controls spectral radiation: Development of
      Chameleon Cool Coating (C3).
AB  - Chameleons have a diagnostic thermal protection that enables them to live under
      various conditions. Our developed special radiative control therefore is inspired
      by the chameleon thermal protection ability by imitating its two superposed
      layers as two pigment particles in one coating layer. One particle imitates a
      chameleon superficial surface for color control (visible light), and another
      particle imitates a deep surface to reflect solar irradiation, especially in the
      near-infrared region. Optical modeling allows us to optimally design the particle
      size and volume fraction. Experimental evaluation shows that the desired spectral
      reflectance, i.e., low in the VIS region and high in NIR region, can be achieved.
      Comparison between the measured and calculated reflectances shows that control of
      the particle size and dispersion/aggregation of particle cloud is important in
      improving the thermal-protection performance of the coating. Using our developed
      coating, the interior temperature decreases and the cooling load is reduced while
      keeping the dark tone of the object.

PMID- 29352223
TI  - ZEB1 confers chemotherapeutic resistance to breast cancer by activating ATM.
AB  - Although zinc finger E-box binding homeobox 1 (ZEB1) has been identified as a key
      factor in the regulation of breast cancer differentiation and metastasis, its
      potential role in modulating tumor chemoresistance has not been fully understood.
      Here, through the study of specimens from a large cohort of human breast cancer
      subjects, we showed that patients with tumors that expressed high levels of ZEB1
      responded poorly to chemotherapy. Moreover, ZEB1 expression was positively
      correlated with expression of B-cell lymphoma-extra large (Bcl-xL) and cyclin D1,
      which are key components of tumor chemoresistant mechanisms. At the molecular
      level, ectopic expression of ZEB1 impaired the responsiveness of breast cancer
      cells to genotoxic drug treatment, such as epirubicin (EPI). During this process,
      ZEB1 transcriptionally activated the expression of ataxia-telangiectasia mutated
      (ATM) kinase by forming a ZEB1/p300/PCAF complex on its promoter, leading to
      increased homologous recombination (HR)-mediated DNA damage repair and the
      clearance of DNA breaks. Using a nude mouse xenograft model, we further confirmed
      that ectopic expression of ZEB1 decreased breast cancer responsiveness to EPI
      treatment in vivo. Collectively, our findings suggest that ZEB1 is a crucial
      determinant of chemotherapeutic resistance in breast cancer.

PMID- 29352224
TI  - Study of an Oxygen Supply and Oxygen Saturation Monitoring System for Radiation
      Therapy Associated with the Active Breathing Coordinator.
AB  - In this study, we designed an oxygen supply and oxygen saturation monitoring
      (OSOSM) system. This OSOSM system can provide a continuous supply of oxygen and
      monitor the peripheral capillary oxygen saturation (SpO2) of patients who accept
      radiotherapy and use an active breathing coordinator (ABC). A clinical test with
      27 volunteers was conducted. The volunteers were divided into two groups based on
      the tendency of SpO2 decline in breath-holding without the OSOSM system: group A
      (12 cases) showed a decline in SpO2 of less than 2%, whereas the decline in SpO2
      in group B (15 cases) was greater than 2% and reached up to 6% in some cases. The
      SpO2 of most volunteers declined during rest. The breath-holding time of group A
      without the OSOSM system was significantly longer than that of group B (p < 0.05)
      and was extended with the OSOSM system by 26.6% and 27.85% in groups A and B,
      respectively. The SpO2 recovery time was reduced by 36.1%, and the total rest
      time was reduced by 27.6% for all volunteers using the OSOSM system. In summary,
      SpO2 declines during breath-holding and rest time cannot be ignored while
      applying an ABC. This OSOSM system offers a simple and effective way to monitor
      SpO2 variation and overcome SpO2 decline, thereby lengthening breath-holding time
      and shortening rest time.

PMID- 29352225
TI  - A humanized mouse model of liver fibrosis following expansion of transplanted
      hepatic stellate cells.
AB  - Hepatic stellate cells (HSCs) are major contributors to liver fibrosis, as
      hepatic injuries may cause their transdifferentiation into myofibroblast-like
      cells capable of producing excessive extracellular matrix proteins. Also, HSCs
      can modulate engraftment of transplanted hepatocytes and contribute to liver
      regeneration. Therefore, understanding the biology of human HSCs (hHSCs) is
      important, but effective methods have not been available to address their fate in
      vivo. To investigate whether HSCs could engraft and repopulate the liver, we
      transplanted GFP-transduced immortalized hHSCs into immunodeficient NOD/SCID
      mice. Biodistribution analysis with radiolabeled hHSCs showed that after
      intrasplenic injection, the majority of transplanted cells rapidly translocated
      to the liver. GFP-immunohistochemistry demonstrated that transplanted hHSCs
      engrafted alongside hepatic sinusoids. Prior permeabilization of the sinusoidal
      endothelial layer with monocrotaline enhanced engraftment of hHSCs. Transplanted
      hHSCs remained engrafted without relevant proliferation in the healthy liver.
      However, after CCl4 or bile duct ligation-induced liver damage, transplanted
      hHSCs expanded and contributed to extracellular matrix production, formation of
      bridging cell-septae and cirrhosis-like hepatic pseudolobules. CCl4-induced
      injury recruited hHSCs mainly to zone 3, whereas after bile duct ligation, hHSCs
      were mainly in zone 1 of the liver lobule. Transplanted hHSCs neither
      transdifferentiated into other cell types nor formed tumors in these settings. In
      conclusion, a humanized mouse model was generated by transplanting hHSCs, which
      proliferated during hepatic injury and inflammation, and contributed to liver
      fibrosis. The ability to repopulate the liver with transplanted hHSCs will be
      particularly significant for mechanistic studies of cell-cell interactions and
      fibrogenesis within the liver.

PMID- 29352226
TI  - Spatio-temporal characteristics of urban air pollutions and their causal
      relationships: Evidence from Beijing and its neighboring cities.
AB  - China has been suffering from serious air pollution for years in response to the
      rapid industrialization and urbanization. Notably Beijing is one of the most
      polluted capitals in the world. Hence, the focus of the study area is on Beijing.
      In the first stage, we analyze spatial and temporal characteristics of air
      pollution of the 6 cities while in the second stage the Granger causality test is
      applied to investigate whether air pollution of a city is affected by its
      neighbors, and vice versa. The findings are the following. Overall, AQI values
      are high in winter and early spring while low in summer and autumn. Among the 6
      cities, Baoding is the major contributor to air pollution in this entire area.
      Besides, Granger causality test results show that there is a unidirectional
      relationship running from Baoding to Beijing and a bidirectional relationship
      between Beijing and Tianjin. In other words, apart from local air pollutants, for
      example, exhaust gas, air quality of Beijing is affected by air pollution of
      Tianjin, and vice versa. However, regarding the relationship between Beijing and
      Baoding, air quality of Beijing is just affected by air pollution of Baoding,
      since Baoding is much polluted than Beijing.

PMID- 29352228
TI  - Dual Band Metamaterial Antenna For LTE/Bluetooth/WiMAX System.
AB  - A compact metamaterial inspired antenna operate at LTE, Bluetooth and WiMAX
      frequency band is introduced in this paper. For the lower band, the design
      utilizes an outer square metallic strip forcing the patch to radiate as an
      equivalent magnetic-current loop. For the upper band, another magnetic current
      loop is created by adding metamaterial structure near the feed line on the patch.
      The metamaterial inspired antenna dimension of 42 * 32 mm2 compatible to wireless
      devices. Finite integration technique based CST Microwave Studio simulator has
      been used to design and numerical investigation as well as lumped circuit model
      of the metamaterial antenna is explained with proper mathematical derivation. The
      achieved measured dual band operation of the conventional antenna are
      sequentially, 0.561~0.578 GHz, 2.346~2.906 GHz, and 2.91~3.49 GHz, whereas the
      metamaterial inspired antenna shows dual-band operation from 0.60~0.64 GHz,
      2.67~3.40 GHz and 3.61~3.67 GHz, respectively. Therefore, the metamaterial
      antenna is applicable for LTE and WiMAX applications. Besides, the measured
      metamaterial antenna gains of 0.15~3.81 dBi and 3.47~3.75 dBi, respectively for
      the frequency band of 2.67~3.40 GHz and 3.61~3.67 GHz.

PMID- 29352227
TI  - LY2087101 and dFBr share transmembrane binding sites in the (alpha4)3(beta2)2
      Nicotinic Acetylcholine Receptor.
AB  - Positive allosteric modulators (PAMs) of nicotinic acetylcholine receptors
      (nAChRs) have potential therapeutic application in neuropathologies associated
      with decrease in function or loss of nAChRs. In this study, we characterize the
      pharmacological interactions of the nAChRs PAM, LY2087101, with the alpha4beta2
      nAChR using mutational and computational analyses. LY2087101 potentiated ACh
      induced currents of low-sensitivity (alpha4)3(beta2)2 and high-sensitivity
      (alpha4)2(beta2)3 nAChRs with similar potencies albeit to a different maximum
      potentiation (potentiation I max  = ~840 and 450%, respectively). Amino acid
      substitutions within the alpha4 subunit transmembrane domain [e.g. alpha4Leu256
      and alpha4Leu260 within the transmembrane helix 1 (TM1); alpha4Phe316 within the
      TM3; and alpha4Gly613 within TM4] significantly reduced LY2087101 potentiation of
      (alpha4)3(beta2)2 nAChR. The locations of these amino acid residues and LY2087101
      computational docking analyses identify two LY2087101 binding sites: an
      intrasubunit binding site within the transmembrane helix bundle of alpha4 subunit
      at the level of alpha4Leu260/alpha4Phe316 and intersubunit binding site at the
      alpha4:alpha4 subunit interface at the level of alpha4Leu256/alpha4Ile315 with
      both sites extending toward the extracellular end of the transmembrane domain. We
      also show that desformylflustrabromine (dFBr) binds to these two sites identified
      for LY2087101. These results provide structural information that are pertinent to
      structure-based design of nAChR allosteric modulators.

PMID- 29352229
TI  - Expression dynamics of miRNAs and their targets in seed germination conditions
      reveals miRNA-ta-siRNA crosstalk as regulator of seed germination.
AB  - Seed germination paves the way for the dormant embryo to establish itself as a
      new plant marking the first critical step in postembryonic plant growth and
      development. Germination starts with the uptake of water (imbibition), followed
      by induction of transcription, translation, energy metabolism, and cell division
      processes. Although small RNAs have been implicated in many developmental
      processes, their role during seed germination stages and conditions remained
      elusive. Here we show that seed germination conditions, like imbibition and
      temperature, dynamically regulate the expression of many developmentally
      important miRNAs and their targets. We have identified 58 miRNAs belonging to 30
      different families at different seed germination conditions. Amongst these, 15
      miRNAs and their targets were significantly differentially expressed in
      Arabidopsis seeds in dry and 12 h, 24 h and 48 h of imbibition. Interestingly,
      differential expression of miR390, which targets trans-acting siRNA locus (TAS3)
      derived transcripts, resulted in alteration of tasiR-ARF mediated regulation of
      expression of target AUXIN RESPONSE FACTORs (ARF2/3/4). Our results suggest that
      the dynamic expression of several miRNAs, their targets, and a crosstalk between
      miRNA and ta-siRNA pathways contribute to the regulation of seed germination in
      Arabidopsis thaliana.

PMID- 29352230
TI  - Histology, immunohistochemistry, and in situ hybridization reveal overlooked
      Ebola virus target tissues in the Ebola virus disease guinea pig model.
AB  - Survivors of Ebola virus infection may become subclinically infected, but whether
      animal models recapitulate this complication is unclear. Using histology in
      combination with immunohistochemistry and in situ hybridization in a
      retrospective review of a guinea pig confirmation-of-virulence study, we
      demonstrate for the first time Ebola virus infection in hepatic oval cells, the
      endocardium and stroma of the atrioventricular valves and chordae tendinae,
      satellite cells of peripheral ganglia, neurofibroblasts and Schwann cells of
      peripheral nerves and ganglia, smooth muscle cells of the uterine myometrium and
      vaginal wall, acini of the parotid salivary glands, thyroid follicular cells,
      adrenal medullary cells, pancreatic islet cells, endometrial glandular and
      surface epithelium, and the epithelium of the vagina, penis and, prepuce. These
      findings indicate that standard animal models for Ebola virus disease are not as
      well-described as previously thought and may serve as a stepping stone for future
      identification of potential sites of virus persistence.

PMID- 29352231
TI  - The Direction of Tumour Growth in Glioblastoma Patients.
AB  - Generating MR-derived growth pattern models for glioblastoma multiforme (GBM) has
      been an attractive approach in neuro-oncology, suggesting a distinct pattern of
      lesion spread with a tendency in growing along the white matter (WM) fibre
      direction for the invasive component. However, the direction of growth is not
      much studied in vivo. In this study, we sought to study the dominant directions
      of tumour expansion/shrinkage pre-treatment. We examined fifty-six GBMs at two
      time-points: at radiological diagnosis and as part of the pre-operative planning,
      both with contrast-enhanced T1-weighted MRIs. The tumour volumes were semi
      automatically segmented. A non-linear registration resulting in a deformation
      field characterizing the changes between the two time points was used together
      with the segmented tumours to determine the dominant directions of tumour change.
      To compute the degree of alignment between tumour growth vectors and WM fibres,
      an angle map was calculated. Our results demonstrate that tumours tend to grow
      predominantly along the WM, as evidenced by the dominant vector population with
      the maximum alignments. Our findings represent a step forward in investigating
      the hypothesis that tumour cells tend to migrate preferentially along the WM.

PMID- 29352232
TI  - The silent healer: miR-205-5p up-regulation inhibits epithelial to mesenchymal
      transition in colon cancer cells by indirectly up-regulating E-cadherin
      expression.
AB  - EMT represents the dominant program within advanced stages of colon cancer, where
      cells acquire migratory characteristics in order to invade secondary tissues and
      form metastasis. Where the majority of the therapeutic strategies are
      concentrated on the reduction of the tumor mass through different apoptotic
      mechanisms, the present study advocates an important role for miR-205-5p in
      impairment of colon cancer cells migration and restoration of the epithelial
      phenotype. Upon identification of a homogenous downregulated profile for miR-205
      5p in colon adenocarcinoma patients, functional studies demonstrated that
      experimental upregulation of this sequence is able to significantly raise the
      levels of E-cadherin through direct inhibition of ZEB1. Moreover, the elevation
      in CDH1 expression was translated into functional parameters where cells lost
      their invasion and migratory characteristics and formed homogenous clusters
      through adhesion interactions. Survival analysis of colon adenocarcinoma patients
      revealed that low levels of miR-205-5p are associated with an unfavorable
      prognostic compared to those with increased expression, demonstrating the
      possible clinical utility of miR-205-5p replacement. Exogenous administration of
      miRNA mimics was not associated with significant changes in cell viability or
      inflammatory pathways. Therefore, the proposed strategy is aiming towards
      inhibition of metastasis and limitation of the tumor borders in advanced stages
      patients in order to prolong the survival time and to increase the efficiency of
      the current therapeutic strategies.

PMID- 29352233
TI  - Hearing capacities and morphology of the auditory system in Serrasalmidae
      (Teleostei: Otophysi).
AB  - Like all otophysan fishes, serrasalmids (piranhas and relatives) possess a
      Weberian apparatus that improves their hearing capacities. We compared the
      hearing abilities among eight species of serrasalmids having different life
      history traits: herbivorous vs. carnivorous and vocal vs. mute species. We also
      made 3D reconstructions of the auditory system to detect potential morphological
      variations associated with hearing ability. The hearing structures were similar
      in overall shape and position. All the species hear in the same frequency range
      and only slight differences were found in hearing thresholds. The eight species
      have their range of best hearing in the lower frequencies (50-900 Hz). In vocal
      serrasalmids, the range of best hearing covers the frequency spectrum of their
      sounds. However, the broad overlap in hearing thresholds among species having
      different life-history traits (herbivorous vs. carnivorous and vocal vs. non
      vocal species) suggests that hearing ability is likely not related to the
      capacity to emit acoustic signals or to the diet, i.e. the ability to detect
      sounds is not associated with a given kind of food. The inner ear appears to be
      highly conservative in this group suggesting that it is shaped by phylogenetic
      history or by other kinds of constraints such as predator avoidance.

PMID- 29352234
TI  - Bi-exponential 3D-T1rho mapping of whole brain at 3 T.
AB  - Detection of multiple relaxation pools using MRI is useful in a number of neuro
      pathologies including multiple sclerosis (MS), Alzheimer's, and stroke. In this
      study we evaluate the feasibility of using T1rho imaging for the detection of bi
      exponential decays in the human brain. A prospective T1rho imaging study was
      performed on model relaxation phantoms (eggs) and 7 healthy volunteers. The data
      was fitted using a single pool and a 2-pool model to estimate mono- and bi
      exponential T1rho maps, respectively. Bi-exponential decays were identified in
      the gray matter (GM) and white matter (WM) of the brain with 40.5% of GM, and
      65.1% of WM pixels showing two T1rho relaxation pools (significance level P <
      0.05). Detection of T1rho based bi-exponential decays in the brain provides
      complimentary information to T2 based contrast regarding the in vivo micro
      environment in the brain.

PMID- 29352235
TI  - Systems modeling accurately predicts responses to genotoxic agents and their
      synergism with BCL-2 inhibitors in triple negative breast cancer cells.
AB  - Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which
      accounts for 15-20% of this disease and is currently treated with genotoxic
      chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the
      process of mitochondrial outer membrane permeabilization (MOMP), which is
      required for the activation of the mitochondrial apoptosis pathway in response to
      genotoxic agents. We previously developed a deterministic systems model of BCL2
      protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo
      mitochondrial apoptosis. Here we determined whether DR_MOMP predicts responses of
      TNBC cells to genotoxic agents and the re-sensitization of resistant cells by
      BCL2 inhibitors. Using absolute protein levels of BAX, BAK, BCL2, BCL(X)L and
      MCL1 as input for DR_MOMP, we found a strong correlation between model
      predictions and responses of a panel of TNBC cells to 24 and 48 h cisplatin (R2 =
      0.96 and 0.95, respectively) and paclitaxel treatments (R2 = 0.94 and 0.95,
      respectively). This outperformed single protein correlations (best performer
      BCL(X)L with R2 of 0.69 and 0.50 for cisplatin and paclitaxel treatments,
      respectively) and BCL2 proteins ratio (R2 of 0.50 for cisplatin and 0.49 for
      paclitaxel). Next we performed synergy studies using the BCL2 selective
      antagonist Venetoclax /ABT199, the BCL(X)L selective antagonist WEHI-539, or the
      MCL1 selective antagonist A-1210477 in combination with cisplatin. In silico
      predictions by DR_MOMP revealed substantial differences in treatment responses of
      BCL(X)L, BCL2 or MCL1 inhibitors combinations with cisplatin that were
      successfully validated in cell lines. Our findings provide evidence that DR_MOMP
      predicts responses of TNBC cells to genotoxic therapy, and can aid in the choice
      of the optimal BCL2 protein antagonist for combination treatments of resistant
      cells.

PMID- 29352236
TI  - Control of neural crest induction by MarvelD3-mediated attenuation of JNK
      signalling.
AB  - Tight junctions are required for the formation of tissue barriers and function as
      suppressors of signalling mechanisms that control gene expression and cell
      behaviour; however, little is known about the physiological and developmental
      importance of such signalling functions. Here, we demonstrate that depletion of
      MarvelD3, a transmembrane protein of tight junctions, disrupts neural crest
      formation and, consequently, development of neural crest-derived tissues during
      Xenopus embryogenesis. Using embryos and explant cultures combined with a small
      molecule inhibitor or mutant mRNAs, we show that MarvelD3 is required to
      attenuate JNK signalling during neural crest induction and that inhibition of JNK
      pathway activation is sufficient to rescue the phenotype induced by MarvelD3
      depletion. Direct JNK stimulation disrupts neural crest development, supporting
      the importance of negative regulation of JNK. Our data identify the junctional
      protein MarvelD3 as an essential regulator of early vertebrate development and
      neural crest induction and, thereby, link tight junctions to the control and
      timing of JNK signalling during early development.

PMID- 29352237
TI  - Wearable Sweat Rate Sensors for Human Thermal Comfort Monitoring.
AB  - We propose watch-type sweat rate sensors capable of automatic natural ventilation
      by integrating miniaturized thermo-pneumatic actuators, and experimentally verify
      their performances and applicability. Previous sensors using natural ventilation
      require manual ventilation process or high-power bulky thermo-pneumatic actuators
      to lift sweat rate detection chambers above skin for continuous measurement. The
      proposed watch-type sweat rate sensors reduce operation power by minimizing
      expansion fluid volume to 0.4 ml through heat circuit modeling. The proposed
      sensors reduce operation power to 12.8% and weight to 47.6% compared to previous
      portable sensors, operating for 4 hours at 6 V batteries. Human experiment for
      thermal comfort monitoring is performed by using the proposed sensors having
      sensitivity of 0.039 (pF/s)/(g/m2h) and linearity of 97.9% in human sweat rate
      range. Average sweat rate difference for each thermal status measured in three
      subjects shows (32.06 +/- 27.19) g/m2h in thermal statuses including
      'comfortable', 'slightly warm', 'warm', and 'hot'. The proposed sensors thereby
      can discriminate and compare four stages of thermal status. Sweat rate
      measurement error of the proposed sensors is less than 10% under air velocity of
      1.5 m/s corresponding to human walking speed. The proposed sensors are applicable
      for wearable and portable use, having potentials for daily thermal comfort
      monitoring applications.

PMID- 29352238
TI  - Molting site fidelity accounts for colony elimination of the Formosan
      subterranean termites (Isoptera: Rhinotermitidae) by chitin synthesis inhibitor
      baits.
AB  - Site fidelity by molting termites in Formosan subterranean termite, Coptotermes
      formosanus Shiraki colonies is a new addition to our understanding of lower
      termites' behavior and biology. Our previous studies indicated that workers moved
      to the central nest to molt in the presence of eggs and reproductives. The
      current study showed that noviflumuron-affected workers also return to the
      central nest and died in the vicinity of reproductives and eggs. The aversion to
      the dead and decaying workers caused reproductives and brood to leave the
      original central nest site in a colony and refuge at newer sites every few days
      in response to newly dead workers near them. Because mortality was an event
      observed only in workers undergoing molting under the effect of noviflumuron- a
      CSI, the death of molting individuals was observed only around reproductives and
      brood. This study reveals a previously undiscovered behavior of molting termites
      and the mechanics behind a successful arsenal; noviflumuron baits used against
      subterranean termites.

PMID- 29352239
TI  - Elucidating the mechanism of the considerable mechanical stiffening of DNA
      induced by the couple Zn2+/Calix[4]arene-1,3-O-diphosphorous acid.
AB  - The couple Calix[4]arene-1,3-O-diphosphorous acid (C4diP) and zinc ions (Zn2+)
      acts as a synergistic DNA binder. Silicon NanoTweezer (SNT) measurements show an
      increase in the mechanical stiffness of DNA bundles by a factor of >150, at Zn2+
      to C4diP ratios above 8, as compared to Zinc alone whereas C4diP alone decreases
      the stiffness of DNA. Electroanalytical measurements using 3D printed devices
      demonstrate a progression of events in the assembly of C4diP on DNA promoted by
      zinc ions. A mechanism at the molecular level can be deduced in which C4diP
      initially coordinates to DNA by phosphate-phosphate hydrogen bonds or in the
      presence of Zn2+ by Zn2+ bridging coordination of the phosphate groups. Then, at
      high ratios of Zn2+ to C4diP, interdigitated dimerization of C4diP is followed by
      cross coordination of DNA strands through Zn2+/C4diP inter-strand interaction.
      The sum of these interactions leads to strong stiffening of the DNA bundles and
      increased inter-strand binding.

PMID- 29352241
TI  - Short Tandem Repeat analysis after Whole Genome Amplification of single B
      lymphoblastoid cells.
AB  - To allow multiple genetic analyses on a single cell, whole genome amplification
      (WGA) is required. Unfortunately, studies comparing different WGA methods for
      downstream human identification Short Tandem Repeat (STR) analysis remain absent.
      Therefore, the aim of this work was to assess the performance of four
      commercially available WGA kits for downstream human identification STR profiling
      on a B-lymphoblastoid cell line. The performance was assessed using an input of
      one or three micromanipulated cells. REPLI-g showed a very low dropout rate, as
      it was the only WGA method in this study that could provide a complete STR
      profile in some of its samples. Although Ampli1, DOPlify and PicoPLEX did not
      detect all selected STR markers, they seem suitable for genetic identification in
      single-cell applications.

PMID- 29352240
TI  - Transcriptome Analysis in Spleen Reveals Differential Regulation of Response to
      Newcastle Disease Virus in Two Chicken Lines.
AB  - Enhancing genetic resistance of chickens to Newcastle Disease Virus (NDV)
      provides a promising way to improve poultry health, and to alleviate poverty and
      food insecurity in developing countries. In this study, two inbred chicken lines
      with different responses to NDV, Fayoumi and Leghorn, were challenged with LaSota
      NDV strain at 21 days of age. Through transcriptome analysis, gene expression in
      spleen at 2 and 6 days post-inoculation was compared between NDV-infected and
      control groups, as well as between chicken lines. At a false discovery rate
      <0.05, Fayoumi chickens, which are relatively more resistant to NDV, showed fewer
      differentially expressed genes (DEGs) than Leghorn chickens. Several interferon
      stimulated genes were identified as important DEGs regulating immune response to
      NDV in chicken. Pathways predicted by IPA analysis, such as "EIF-signaling",
      "actin cytoskeleton organization nitric oxide production" and "coagulation
      system" may contribute to resistance to NDV in Fayoumi chickens. The identified
      DEGs and predicted pathways may contribute to differential responses to NDV
      between the two chicken lines and provide potential targets for breeding chickens
      that are more resistant to NDV.

PMID- 29352242
TI  - PTRE-seq reveals mechanism and interactions of RNA binding proteins and miRNAs.
AB  - RNA binding proteins (RBP) and microRNAs (miRNAs) often bind sequences in 3'
      untranslated regions (UTRs) of mRNAs, and regulate stability and translation
      efficiency. With the identification of numerous RBPs and miRNAs, there is an
      urgent need for new technologies to dissect the function of the cis-acting
      elements of RBPs and miRNAs. We describe post-transcriptional regulatory element
      sequencing (PTRE-seq), a massively parallel method for assaying the target
      sequences of miRNAs and RBPs. We use PTRE-seq to dissect sequence preferences and
      interactions between miRNAs and RBPs. The binding sites for these effector
      molecules influenced different aspects of the RNA lifecycle: RNA stability,
      translation efficiency, and translation initiation. In some cases, post
      transcriptional control is modular, with different factors acting independently
      of each other, while in other cases factors show specific epistatic interactions.
      The throughput, flexibility, and reproducibility of PTRE-seq make it a valuable
      tool to study post-transcriptional regulation by 3'UTR elements.

PMID- 29352243
TI  - Nucleolin and ErbB2 inhibition reduces tumorigenicity of ErbB2-positive breast
      cancer.
AB  - ErbB2, a member of the ErbB family of receptor tyrosine kinases, is an essential
      player in the cell's growth and proliferation signaling pathways. Amplification
      or overexpression of ErbB2 is observed in ~30% of breast cancer patients, and
      often drives cellular transformation and cancer development. Recently, we have
      shown that ErbB2 interacts with the nuclear-cytoplasmic shuttling protein
      nucleolin, an interaction which enhances cell transformation in vitro, and
      increases mortality risk and disease progression rate in human breast cancer
      patients. Given these results, and since acquired resistance to anti-ErbB2
      targeted therapy is a major obstacle in treatment of breast cancer, we have
      examined the therapeutic potential of targeting the ErbB2-nucleolin complex. The
      effect of the nucleolin-specific inhibitor GroA (AS1411) on ErbB2-positive breast
      cancer was tested in vivo, in a mouse xenograft model for breast cancer; as well
      as in vitro, alone and in combination with the ErbB2 kinase-inhibitor tyrphostin
      AG-825. Here, we show that in vivo treatment of ErbB2-positive breast tumor
      xenografts with GroA reduces tumor size and leads to decreased ErbB2-mediated
      signaling. Moreover, we found that co-treatment of breast cancer cell lines with
      GroA and the ErbB2 kinase-inhibitor tyrphostin AG-825 enhances the anti-cancer
      effects exerted by GroA alone in terms of cell viability, mortality, migration,
      and invasiveness. We, therefore, suggest a novel therapeutic approach, consisting
      of combined inhibition of ErbB2 and nucleolin, which has the potential to improve
      breast cancer treatment efficacy.

PMID- 29352244
TI  - A very large perpendicular magnetic anisotropy in Pt/Co/MgO trilayers fabricated
      by controlling the MgO sputtering power and its thickness.
AB  - The perpendicular magnetic anisotropy (PMA) properties of Pt/Co/MgO trilayers are
      investigated as a function of the MgO sputtering power (PMgO) and its thickness
      (tMgO), both of which are important parameters affecting the degree of oxygen
      interpenetration into Co during sputtering. A strong PMA is achieved at small
      values of PMgO and tMgO, where the oxygen interpenetration into Co is expected to
      be small. The range of oxygen interpenetration is relatively extended in such a
      way that it affects both the Pt/Co and Co/MgO interfaces. The PMA properties of
      as-deposited samples are improved by post-annealing for temperatures up to 400 
      degrees C examined in this study, probably due to the diffusion of the
      interpenetrated oxygen atoms toward the Co/MgO interface. In a structure of Pt/Co
      (0.6 nm)/MgO (2 nm), which is fabricated at PMgO = 50 W and then annealed at 400 
      degrees C, a huge saturation field is achieved (over 40 kOe) indicating a very
      strong PMA. Between the two interfaces of Pt/Co and Co/MgO, the PMA is mainly due
      to the former in the as-deposited state, but the contribution of the latter
      increases with the increase in the annealing temperature.

PMID- 29352245
TI  - AV2 protein of tomato leaf curl Palampur virus promotes systemic necrosis in
      Nicotiana benthamiana and interacts with host Catalase2.
AB  - Tomato leaf curl Palampur virus (ToLCPalV) is a whitefly-transmitted, bipartite
      begomovirus. Here, we demonstrated that ectopic expression of AV2 from a Potato
      virus X (PVX)-based vector accelerated systemic necrosis and reactive oxygen
      species (ROS) accumulation in Nicotiana benthamiana. Furthermore, 10 amino acids
      from N-terminal region of AV2 were found to be associated with the systemic
      necrosis symptom/phenotype. Mutational studies of ToLCPalV infectious clones
      lacking the AV2 revealed that AV2 is essential for the systemic movement of DNA
      A, symptom severity and viral DNA accumulation. In a yeast two-hybrid assay,
      Catalase2 (Cat2) was found to associate with AV2 protein. Further, silencing of
      Cat2 resulted in appearance of necrotic lesions on N. benthamiana and these
      plants were highly susceptible to ToLCPalV infection in comparison to control
      plants. Infection ToLCPalV on Solanum lycopersicum resulted in downregulation of
      Cat2 transcripts, followed by accumulation of ROS and stress marker transcripts.
      The AV2 protein also suppressed virus-induced gene silencing (VIGS) of the
      Phytoene desaturase (PDS) gene. Our results show that AV2 is essential for the
      pathogenicity, systemic movement and suppression of gene silencing in the host.
      Altogether, our findings suggest that interactions between AV2 and Cat2 might
      play a crucial role in the establishment of ToLCPalV infection.

PMID- 29352246
TI  - U-box ubiquitin ligase PPIL2 suppresses breast cancer invasion and metastasis by
      altering cell morphology and promoting SNAI1 ubiquitination and degradation.
AB  - Metastasis is the leading cause of breast cancer fatalities. To develop new
      therapeutic strategies, the mechanisms underlying breast cancer invasion and
      metastasis need to be further investigated. Peptidylprolyl isomerase
      (cyclophilin)-like 2 (PPIL2) is a U-box-type E3 ubiquitin ligase belonging to the
      cyclophilin family. Proteins within this family are the major cytosolic binding
      proteins of the immunosuppressant drug cyclosporine A (CsA). Although PPIL2 has
      been reported to potentially be involved in cell migration, its role in breast
      cancer is still unclear. Herein, we demonstrate that PPIL2 suppressed metastasis
      in a breast cancer model by altering cell morphology and suppressing the
      epithelial-mesenchymal transition (EMT) process. Moreover, elevated PPIL2
      inhibited EMT and breast cancer invasion by interacting with the classical EMT
      transcription factor, SNAI1, to enhance its ubiquitin-dependent degradation.
      Furthermore, PPIL2 protein level and stability was upregulated after CsA
      treatment, indicating that PPIL2 might be involved in CsA-mediated repression of
      EMT in breast cancer. Analysis of tissue samples taken from breast cancer
      patients showed a significant correlation between the expression of PPIL2 and the
      degree of cancer invasion and metastasis. In summary, these results would shed
      light on a potential clinical use of CsA in breast cancer patients.

PMID- 29352247
TI  - High content analysis identifies unique morphological features of reprogrammed
      cardiomyocytes.
AB  - Direct reprogramming of fibroblasts into cardiomyocytes is a promising approach
      for cardiac regeneration but still faces challenges in efficiently generating
      mature cardiomyocytes. Systematic optimization of reprogramming protocols
      requires scalable, objective methods to assess cellular phenotype beyond what is
      captured by transcriptional signatures alone. To address this question, we
      automatically segmented reprogrammed cardiomyocytes from immunofluorescence
      images and analyzed cell morphology. We also introduce a method to quantify
      sarcomere structure using Haralick texture features, called SarcOmere Texture
      Analysis (SOTA). We show that induced cardiac-like myocytes (iCLMs) are highly
      variable in expression of cardiomyocyte markers, producing subtypes that are not
      typically seen in vivo. Compared to neonatal mouse cardiomyocytes, iCLMs have
      more variable cell size and shape, have less organized sarcomere structure, and
      demonstrate reduced sarcomere length. Taken together, these results indicate that
      traditional methods of assessing cardiomyocyte reprogramming by quantifying
      induction of cardiomyocyte marker proteins may not be sufficient to predict
      functionality. The automated image analysis methods described in this study may
      enable more systematic approaches for improving reprogramming techniques above
      and beyond existing algorithms that rely heavily on transcriptome profiling.

PMID- 29352249
TI  - Guided cracking of electrodes by stretching prism-patterned membrane electrode
      assemblies for high-performance fuel cells.
AB  - Guided cracks were successfully generated in an electrode using the concentrated
      surface stress of a prism-patterned Nafion membrane. An electrode with guided
      cracks was formed by stretching the catalyst-coated Nafion membrane. The
      morphological features of the stretched membrane electrode assembly (MEA) were
      investigated with respect to variation in the prism pattern dimension (prism
      pitches of 20 MUm and 50 MUm) and applied strain (S ~ 0.5 and 1.0). The behaviour
      of water on the surface of the cracked electrode was examined using environmental
      scanning electron microscopy. Guided cracks in the electrode layer were shown to
      be efficient water reservoirs and liquid water passages. The MEAs with and
      without guided cracks were incorporated into fuel cells, and electrochemical
      measurements were conducted. As expected, all MEAs with guided cracks exhibited
      better performance than conventional MEAs, mainly because of the improved water
      transport.

PMID- 29352248
TI  - Combined use of EpCAM and FRalpha enables the high-efficiency capture of
      circulating tumor cells in non-small cell lung cancer.
AB  - Circulating tumor cells (CTCs) provide a new approach for auxiliary diagnosis,
      therapeutic effect evaluation, and prognosis prediction for cancer patients. The
      epithelial cell adhesion molecule (EpCAM)-based separation method (CellSearch)
      showed good clinical use in multiple types of cancer. Nevertheless, some non
      small cell lung cancer (NSCLC) tumor cells have a lower expression of EpCAM and
      are less frequently detected by CellSearch. Here, we present a highly sensitive
      immunomagnetic separation method to capture CTCs based on two cell surface
      markers for NSCLC, EpCAM and Folate receptor alpha (FRalpha). Our method has been
      demonstrated to be more efficient in capturing NSCLC cells (P < 0.01) by
      enriching three types of CTCs: EpCAM+/FRalpha-/low, EpCAM-/low/FRalpha+, and
      EPCAM+/FRalpha+. In 41 NSCLC patients, a significantly higher CTC capture rate
      (48.78% vs. 73.17%) was obtained, and by using a cutoff value of 0 CTC per 2 ml
      of blood, the sensitivities were 53.66% and 75.61% and the specificities were
      100% and 90% for anti-EpCAM-MNs or a combination of anti-EpCAM-MNs and anti
      FRalpha-MNs, respectively. Compared with the tumor-specific LT-PCR based on
      FRalpha, our method can isolate intact FRalpha+ CTCs, and it is advantageous for
      additional CTC-related downstream analysis. Our results provide a new method to
      increase the CTC capture efficiency of NSCLC.

PMID- 29352250
TI  - Multi-species coexistence in Lotka-Volterra competitive systems with crowding
      effects.
AB  - Classical Lotka-Volterra (LV) competition equation has shown that coexistence of
      competitive species is only possible when intraspecific competition is stronger
      than interspecific competition, i.e., the species inhibit their own growth more
      than the growth of the other species. Note that density effect is assumed to be
      linear in a classical LV equation. In contrast, in wild populations we can
      observed that mortality rate often increases when population density is very
      high, known as crowding effects. Under this perspective, the aggregation models
      of competitive species have been developed, adding the additional reduction in
      growth rates at high population densities. This study shows that the coexistence
      of a few species is promoted. However, an unsolved question is the coexistence of
      many competitive species often observed in natural communities. Here, we build an
      LV competition equation with a nonlinear crowding effect. Our results show that
      under a weak crowding effect, stable coexistence of many species becomes
      plausible, unlike the previous aggregation model. An analysis indicates that
      increased mortality rate under high density works as elevated intraspecific
      competition leading to the coexistence. This may be another mechanism for the
      coexistence of many competitive species leading high species diversity in nature.

PMID- 29352251
TI  - Differential effects of SUMO1 and SUMO3 on PKR activation and stability.
AB  - Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is a serine/threonine
      kinase that exerts its own phosphorylation and the phosphorylation of the alpha
      subunit of the protein synthesis initiation factor eIF-2alpha. PKR was identified
      as a target of SUMOylation and the triple PKR-SUMO deficient mutant on Lysine
      residues K60-K150-K440 has reduced PKR activity. We report that SUMO1 and SUMO3
      expression exert differential effects on PKR localization, activation and
      stability. SUMO1 or SUMO3 did not alter the repartition of PKR in the cytoplasm
      and the nucleus. However, in SUMO3-expressing cells PKR was found more
      concentrated around the perinuclear membrane and was recruited from small
      speckles to nuclear dots. Interestingly, SUMO1 expression alone resulted in PKR
      and eIF-2alpha activation, whereas SUMO3 reduced PKR and eIF-2alpha activation
      upon viral infection or dsRNA transfection. In addition, encephalomyocarditis
      virus (EMCV) enhanced PKR conjugation to SUMO1 and SUMO3 but only SUMO3
      expression promoted caspase-dependent EMCV-induced PKR degradation. Furthermore,
      the higher EMCV-induced PKR activation by SUMO1 was correlated with an inhibition
      of EMCV. Importantly SUMO1, by inducing PKR activation in the absence of viral
      infection, and SUMO3, by counteracting both PKR activation and stability upon
      viral infection, shed a new light on the differential effects of SUMO-modified
      PKR.

PMID- 29352252
TI  - Towards an experimental classification system for membrane active peptides.
AB  - Mature proteins can act as potential sources of encrypted bioactive peptides
      that, once released from their parent proteins, might interact with diverse
      biomolecular targets. In recent work we introduced a systematic methodology to
      uncover encrypted intragenic antimicrobial peptides (IAPs) within large protein
      sequence libraries. Given that such peptides may interact with membranes in
      different ways, resulting in distinct observable outcomes, it is desirable to
      develop a predictive methodology to categorize membrane active peptides and
      establish a link to their physicochemical properties. Building upon previous
      work, we explored the interaction of a range of IAPs with model membranes probed
      by differential scanning calorimetry (DSC) and circular dichroism (CD)
      techniques. The biophysical data were submitted to multivariate statistical
      methods and resulting peptide clusters were correlated to peptide structure and
      to their antimicrobial activity. A re-evaluation of the physicochemical
      properties of the peptides was conducted based on peptide cluster memberships.
      Our data indicate that membranolytic peptides produce characteristic thermal
      transition (DSC) profiles in model vesicles and that this can be used to
      categorize novel molecules with unknown biological activity. Incremental
      expansion of the model presented here might result in a unified experimental
      framework for the prediction of novel classes of membrane active peptides.

PMID- 29352253
TI  - Tracking the Evolution of Transiently Transfected Individual Cells in a
      Microfluidic Platform.
AB  - Transient gene expression (TGE) technology enables the rapid production of large
      amount of recombinant proteins, without the need of fastidious screening of the
      producing cells required for stable transfection (ST). However, several barriers
      must be overcome before reaching the production yields using ST. For optimizing
      the production yields from suspended cells using TGE, a better understanding of
      the transfection conditions at the single cell level are required. In this study,
      a universal droplet microfluidic platform was used to assess the heterogeneities
      of CHO-S population transiently transfected with cationic liposomes (CL)
      (lipoplexes) complexed with GFP-coding plasmid DNA (pDNA). A single cell analysis
      of GFP production kinetics revealed the presence of a subpopulation producing
      higher levels of GFP compared with the main population. The size of high
      producing (HP) cells, their relative abundance, and their specific productivity
      were dependent on the charge and the pDNA content of the different lipoplexes:
      HPs showed increased cell size in comparison to the average population,
      lipoplexes with positive charge produced more HPs, and lipoplexes carrying a
      larger amount of pDNA yielded a higher specific productivity of HPs. This study
      demonstrates the potential for time-resolved single-cell measurements to explain
      population dynamics from a microscopic point of view.

PMID- 29352254
TI  - Author Correction: Long-term carbon sink in Borneo's forests halted by drought
      and vulnerable to edges.
AB  - The original version of this Article contained an error in the third sentence of
      the abstract and incorrectly read "Here, using long-term plot monitoring records
      of up to half a century, we find that intact forests in Borneo gained 0.43 Mg C
      ha-1 year-1 (95% CI 0.14-0.72, mean period 1988-2010) above-ground live biomass",
      rather than the correct "Here, using long-term plot monitoring records of up to
      half a century, we find that intact forests in Borneo gained 0.43 Mg C ha-1 year
      1 (95% CI 0.14-0.72, mean period 1988-2010) in above-ground live biomass carbon".
      This has now been corrected in both the PDF and HTML versions of the Article.

PMID- 29352255
TI  - Offline stimulation of human parietal cortex differently affects resting EEG
      microstates.
AB  - The interference effects of transcranial magnetic stimulation (TMS) on several
      electroencephalographic (EEG) measures in both temporal and frequency domains
      have been reported. We tested the hypothesis whether the offline external
      inhibitory interference, although focal, could result in a global reorganization
      of the functional brain state, as assessed by EEG microstates. In 16 healthy
      subjects, we inhibited five parietal areas and used a pseudo stimulation (Sham)
      at rest. The EEG microstates were extracted before and after each stimulation.
      The canonical A, B, C and D templates were found before and after all stimulation
      conditions. The Sham, as well as the stimulation of a ventral site did not modify
      any resting EEG microstates' topography. On the contrary, interfering with
      parietal key-nodes of both dorsal attention (DAN) and default mode networks
      (DMN), we observed that the microstate C clearly changes, whereas the other three
      topographies are not affected. These results provide the first causal evidence of
      a microstates modification following magnetic interference. Since the microstate
      C has been associated to the activity in regions belonging to the cingulo
      opercular network (CON), the regional specificity of such inhibition seems to
      support the theory of a link between CON and both DAN and DMN at rest.

PMID- 29352256
TI  - Time management in a co-housed social rodent species (Arvicanthis niloticus).
AB  - Sociality has beneficial effects on fitness, and timing the activities of animals
      may be critical. Social cues could influence daily rhythmic activities via direct
      effects on the circadian clock or on processes that bypass it (masking), but
      these possibilities remain incompletely addressed. We investigated the effects of
      social cues on the circadian body temperature (Tb) rhythms in pairs of co-housed
      and isolated grass rats, Arvicanthis niloticus (a social species), in constant
      darkness (DD). Cohabitation did not induce synchronization of circadian Tb
      rhythms. However, socio-sexual history did affect circadian properties:
      accelerating the clock in sexually experienced males and females in DD and
      advancing rhythm phase in the females in a light-dark cycle. To address whether
      synchronization occurs at an ultradian scale, we analyzed Tb and activity rhythms
      in pairs of co-housed sisters or couples in DD. Regardless of pair type, co
      housing doubled the percentage of time individuals were simultaneously active
      without increasing individual activity levels, suggesting that activity bouts
      were synchronized by redistribution over 24 h. Together, our laboratory findings
      show that social cues affect individual "time allocation" budgets via mechanisms
      at multiple levels of biological organization. We speculate that in natural
      settings these effects could be adaptive, especially for group-living animals.

PMID- 29352257
TI  - Robust phenotype prediction from gene expression data using differential
      shrinkage of co-regulated genes.
AB  - Discovery of robust diagnostic or prognostic biomarkers is a key to optimizing
      therapeutic benefit for select patient cohorts - an idea commonly referred to as
      precision medicine. Most discovery studies to derive such markers from high
      dimensional transcriptomics datasets are weakly powered with sample sizes in the
      tens of patients. Therefore, highly regularized statistical approaches are
      essential to making generalizable predictions. At the same time, prior knowledge
      driven approaches have been successfully applied to the manual interpretation of
      high-dimensional transcriptomics datasets. In this work, we assess the impact of
      combining two orthogonal approaches for the discovery of biomarker signatures,
      namely (1) well-known lasso-based regression approaches and its more recent
      derivative, the group lasso, and (2) the discovery of significant upstream
      regulators in literature-derived biological networks. Our method integrates both
      approaches in a weighted group-lasso model and differentially weights gene sets
      based on inferred active regulatory mechanism. Using nested cross-validation as
      well as independent clinical datasets, we demonstrate that our approach leads to
      increased accuracy and generalizable results. We implement our approach in a
      computationally efficient, user-friendly R package called creNET. The package can
      be downloaded at
      https://github.com/kouroshz/creNethttps://github.com/kouroshz/creNet and is
      accompanied by a parsed version of the STRING DB data base.

PMID- 29352258
TI  - Atomic structure and passivated nature of the Se-treated GaAs(111)B surface.
AB  - We have systematically studied the atomic structure and electronic properties of
      the Se-treated GaAs(111)B surface using scanning tunneling microscopy, reflection
      high-energy electron diffraction, x-ray photoelectron spectroscopy, and first
      principles calculations. We have found that Se atoms substitute [Formula: see
      text] monolayer of As atoms at the outermost layer of the ideal (111)B surface.
      Charge transfer from Se to As eliminates all of unsaturated dangling bonds, so
      that the surface is electronically stabilized, leaving no surface states in the
      mid-gap region.

PMID- 29352259
TI  - Plasma MCP-1 and Cognitive Decline in Patients with Alzheimer's Disease and Mild
      Cognitive Impairment: A Two-year Follow-up Study.
AB  - Monocyte chemoattractant protein-1 (MCP-1, also known as chemokine CCL2) is a
      vital chemokine that mediates inflammation in Alzheimer's disease (AD). We
      analyzed the associations between the baseline plasma MCP-1 level, longitudinal
      cognitive changes, and genetic effects of CCL2 rs1024611 and its receptor, CC
      chemokine receptor 2 (CCR2) rs1799864, in AD. In total, 310 AD patients and 66
      mild cognitive impairment (MCI) patients were followed for 2 years, and 120
      controls were recruited at baseline for comparison. After adjusting for
      covariates using one-way analysis of covariance, AD patients had higher plasma
      MCP-1 levels compared with MCI patients and controls, and severe AD patients had
      the highest levels. After adjusting for covariates using generalized estimating
      equation analysis, the results showed that the baseline MCP-1 level was
      significantly correlated with changes in the two-year Mini-Mental Status
      Examination (p = 0.046). The A allele of CCR2 rs1799864 was associated with a
      higher MCP-1 level in AD and MCI patients. In conclusion, plasma MCP-1 might
      reflect the risk and disease course of AD. A higher plasma MCP-1 level is
      associated with greater severity and faster cognitive decline. Additionally, the
      CCR2 polymorphism may play a role in the regulation of MCP-1/CCR2 signaling in
      AD.

PMID- 29352260
TI  - Effect of in vitro storage duration on measured mechanical properties of brain
      tissue.
AB  - Accurate characterization of the mechanical properties of brain tissue is
      essential for understanding the mechanisms of traumatic brain injuries and
      developing protective gears or facilities. However, how storage conditions might
      affect the mechanical properties of brain tissue remains unclear. The objective
      of this study is to investigate the effect of in vitro storage duration on the
      mechanical performance of brain tissue since measurements are usually carried out
      in vitro. Differential Scanning Calorimetry (DSC) measurements and uniaxial
      compression mechanical experiments are carried out. The results indicate that,
      for brain tissue stored at 1  degrees C without any liquid medium, the bio
      molecular interactions and the mechanical strength of both white and grey matter
      deteriorate with prolonged storage duration. Transmission Electron Microscopy
      (TEM) results reveal the degeneration of myelin sheaths and the vacuolization of
      cristae with prolonged storage duration, suggesting that the in vitro storage
      duration should be carefully controlled. The findings from this study might
      facilitate the development of guidelines and standards for the in vitro storage
      of brain tissue.

PMID- 29352261
TI  - Insight into the role of PIKK family members and NF-kB in DNAdamage-induced
      senescence and senescence-associated secretory phenotype of colon cancer cells.
AB  - Senescence of cancer cells is an important outcome of treatment of many cancer
      types. Cell senescence is a permanent cell cycle arrest induced by stress
      conditions, including DNA damage. DNA damage activates DNA damage response (DDR),
      which involves members of the phosphatidylinositol 3-kinase-related kinase (PIKK)
      superfamily: protein kinases ATM, ATR, and DNA-PKcs. The so-far collected data
      indicate that ATM, with its downstream targets CHK2, p53, and p21, is the key
      protein involved in DDR-dependent senescence. It was also documented that the so
      called senescence-associated secretory phenotype-SASP relies on ATM/CHK2, and not
      on p53 signaling. Moreover, genotoxic agents used in cancer treatment can
      activate NF-kappaB, which also induces transcription of SASP genes. In this
      paper, we have studied the involvement of three PIKK family members in colon
      cancer cell senescence and connection between DNA-damage-induced senescence and
      NF-kappaB-regulated SASP in p53-proficient and p53-deficient colon cancer cells
      treated with doxorubicin. We showed that doxorubicin induced cell senescence in
      both p53+/+ and p53-/- HCT116 cells, proving that this process is p53
      independent. Senescence was successfully abrogated by a PIKK inhibitor, caffeine,
      or by simultaneous silencing of three PIKKs by specific siRNAs. By silencing
      individual members of PIKK family and analyzing common markers of senescence, the
      level of p21 and SA-beta-Gal activity, we came to the conclusion that ATR kinase
      is crucial for the onset of senescence as, in contrast to ATM and DNA-PKsc, it
      could not be fully substituted by other PIKKs. Moreover, we showed that in case
      of silencing the three PIKKs, there was no SASP reduction accompanying the
      decrease in the level of p21 and SA-beta-Gal (Senescence-Associated-beta
      Galactosidase) activity; whereas knocking down the NF-kappaB component, p65,
      abrogated SASP, but did not affect other markers of senescence, proving that DNA
      damage regulated senescence independently and NF-kappaB evoked SASP.

PMID- 29352262
TI  - Microbial regulation of the L cell transcriptome.
AB  - L cells are an important class of enteroendocrine cells secreting hormones such
      as glucagon like peptide-1 and peptide YY that have several metabolic and
      physiological effects. The gut is home to trillions of bacteria affecting host
      physiology, but there has been limited understanding about how the microbiota
      affects gene expression in L cells. Thus, we rederived the reporter mouse strain,
      GLU-Venus expressing yellow fluorescent protein under the control of the
      proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and
      conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to
      transcriptomic profiling. We observed that the microbiota exerted major effects
      on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota
      suppressed biological processes related to vesicle localization and synaptic
      vesicle cycling in Lpos cells from ileum. This finding was corroborated by
      electron microscopy of Lpos cells showing reduced numbers of vesicles as well as
      by demonstrating decreased intracellular GLP-1 content in primary cultures from
      ileum of CONV-R compared with GF GLU-Venus mice. By analysing Lpos cells
      following colonization of GF mice we observed that the greatest transcriptional
      regulation was evident within 1 day of colonization. Thus, the microbiota has a
      rapid and pronounced effect on the L cell transcriptome, predominantly in the
      ileum.

PMID- 29352263
TI  - Mammalian endoreplication emerges to reveal a potential developmental timer.
AB  - Among the most intriguing and relevant questions in physiology is how developing
      tissues correctly coordinate proliferation with differentiation. Endoreplication,
      in a broad sense, is a consequence of a cell division block in the presence of an
      active cell cycle, and it typically occurs as cells differentiate terminally to
      fulfill a specialised function. Until recently, endoreplication was thought to be
      a rare variation of the cell cycle in mammals, more common in invertebrates and
      plants. However, in the last years, endoreplication has been uncovered in various
      tissues in mammalian organisms, including human. A recent report showing that
      cells in the mammary gland become binucleate at lactation sheds new insight into
      the importance of mammalian polyploidisation. We here propose that
      endoreplication is a widespread phenomenon in mammalian developing tissues that
      results from an automatic, robust and simple self-limiting mechanism coordinating
      cell multiplication with differentiation. This mechanism might act as a
      developmental timer. The model has implications for homeostasis control and
      carcinogenesis.

PMID- 29352264
TI  - Cell autonomous role of iASPP deficiency in causing cardiocutaneous disorders.
AB  - Desmosome components are frequently mutated in cardiac and cutaneous disorders in
      animals and humans and enhanced inflammation is a common feature of these
      diseases. Previous studies showed that inhibitor of Apoptosis Stimulating p53
      Protein (iASPP) regulates desmosome integrity at cell-cell junctions and
      transcription in the nucleus, and its deficiency causes cardiocutaneous disorder
      in mice, cattle, and humans. As iASPP is a ubiquitously expressed shuttling
      protein with multiple functions, a key question is whether the observed
      cardiocutaneous phenotypes are caused by loss of a cell autonomous role of iASPP
      in cardiomyocytes and keratinocytes specifically or by a loss of iASPP in other
      cell types such as immune cells. To address this, we developed cardiomyocyte
      specific and keratinocyte-specific iASPP-deficient mouse models and show that the
      cell-type specific loss of iASPP in cardiomyocytes or keratinocytes is sufficient
      to induce cardiac or cutaneous disorders, respectively. Additionally,
      keratinocyte-specific iASPP-deficient mice have delayed eyelid development and
      wound healing. In keratinocytes, junctional iASPP is critical for stabilizing
      desmosomes and iASPP deficiency results in increased and disorganized cell
      migration, as well as impaired cell adhesion, consistent with delayed wound
      healing. The identification of a cell autonomous role of iASPP deficiency in
      causing cardiocutaneous syndrome, impaired eyelid development and wound healing
      suggests that variants in the iASPP gene also may contribute to polygenic heart
      and skin diseases.

PMID- 29352265
TI  - Type I IFN operates pyroptosis and necroptosis during multidrug-resistant A.
      baumannii infection.
AB  - Multidrug-resistant Acinetobacter baumannii, a common pathogen responsible for
      nosocomial infections, is the main cause for outbreaks of infectious diseases,
      such as pneumonia, meningitis, and bacteremia, especially among critically ill
      patients. Epidemic A. baumannii is a growing public health concern as it is
      resistant to all existing antimicrobial agents, thereby necessitating the
      development of new therapeutic approaches to mount an effective immune response
      against this bacterial pathogen. In this study, we identified a critical role for
      type I interferon (IFN) in epigenetic regulation during A. baumannii infection
      and established a central role for it in multiple cell death pathways. A.
      baumannii infection induced mixed cell death constituted of apoptosis,
      pyroptosis, and necroptosis. Mechanically, A. baumannii triggered TRIF-dependent
      type I IFN production, which in turn induced the expression of genes Zbp1, Mlkl,
      caspase-11, and Gsdmd via KAT2B-mediated and P300-mediated H3K27ac modification,
      leading to NLRP3 inflammasome activation, and potentially contributed to GSDMD
      mediated pyroptosis and MLKL-dependent necroptosis. Our study offers novel
      insights into the mechanisms of type I IFN and provides potential therapeutic
      targets for infectious and inflammatory diseases.

PMID- 29352266
TI  - Correspondence: T cells are compromised in tetracycline transactivator transgenic
      mice.

PMID- 29352267
TI  - Differential susceptibility of striatal, hippocampal and cortical neurons to
      Caspase-6.
AB  - Active cysteinyl protease Caspase-6 is associated with early Alzheimer and
      Huntington diseases. Higher entorhinal cortex and hippocampal Caspase-6 levels
      correlate with lower cognitive performance in aged humans. Caspase-6 induces
      axonal degeneration in human primary neuron cultures and causes inflammation and
      neurodegeneration in mouse hippocampus, and age-dependent memory impairment. To
      assess whether Caspase-6 causes damage to another neuronal system, a transgenic
      knock-in mouse overexpressing a self-activated form of Caspase-6 five-fold in the
      striatum, the area affected in Huntington disease, and 2.5-fold in the
      hippocampus and cortex, was generated. Detection of Tubulin cleaved by Caspase-6
      confirmed Caspase-6 activity. The Caspase-6 expressing mice and control
      littermates were subjected to behavioral tests to assess Huntington disease
      relevant psychiatric, motor, and cognitive deficits. Depression was excluded with
      the forced swim and sucrose consumption tests. Motor deficits were absent in the
      nesting, clasping, rotarod, vertical pole, gait, and open field analyzes.
      However, Caspase-6 mice developed age-dependent episodic and spatial memory
      deficits identified by novel object recognition, Barnes maze and Morris water
      maze assays. Neuron numbers were maintained in the striatum, hippocampus, and
      cortex. Microglia and astrocytes were increased in the hippocampal stratum
      lacunosum molecular and in the cortex, but not in the striatum. Synaptic mRNA
      profiling identified two differentially expressed genes in transgenic
      hippocampus, but none in striatum. Caspase-6 impaired synaptic transmission and
      induced neurodegeneration in hippocampal CA1 neurons, but not in striatal medium
      spiny neurons. These data revealed that active Caspase-6 in the striatal medium
      spiny neurons failed to induce inflammation, neurodegeneration or behavioral
      abnormalities, whereas active Caspase-6 in the cortex and hippocampus impaired
      episodic and spatial memories, and induced inflammation, neuronal dysfunction,
      and neurodegeneration. The results indicate age and neuronal subtype-dependent
      Caspase-6 toxicity and highlight the importance of targeting the correct neuronal
      subtype to identify underlying molecular mechanisms of neurodegenerative
      diseases.

PMID- 29352268
TI  - Cylindromatosis mediates neuronal cell death in vitro and in vivo.
AB  - The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key
      regulator of cell proliferation and inflammation. A genome-wide siRNA screen
      linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis;
      however, the exact mechanisms of CYLD-mediated cell death remain unknown.
      Therefore, we investigated the precise role of CYLD in models of neuronal cell
      death in vitro and evaluated whether CYLD deletion affects brain injury in vivo.
      In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented
      RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death.
      Similar protective effects were achieved by siRNA silencing of RIP1 or RIP3 or by
      pharmacological inhibition of RIP1 with necrostatin-1. In vivo, CYLD knockout
      mice were protected from trauma-induced brain damage compared to wild-type
      littermate controls. These findings unravel the mechanisms of CYLD-mediated cell
      death signaling in damaged neurons in vitro and suggest a cell death-mediating
      role of CYLD in vivo.

PMID- 29352269
TI  - Phosphorylation by protein kinase A disassembles the caspase-9 core.
AB  - Caspases, the cysteine proteases which facilitate the faithful execution of
      apoptosis, are tightly regulated by a number of mechanisms including
      phosphorylation. In response to cAMP, PKA phosphorylates caspase-9 at three sites
      preventing caspase-9 activation, and suppressing apoptosis progression.
      Phosphorylation of caspase-9 by PKA at the functionally relevant site Ser-183
      acts as an upstream block of the apoptotic cascade, directly inactivating caspase
      9 by a two-stage mechanism. First, Ser-183 phosphorylation prevents caspase-9
      self-processing and directly blocks substrate binding. In addition, Ser-183
      phosphorylation breaks the fundamental interactions within the caspase-9 core,
      promoting disassembly of the large and small subunits. This occurs despite Ser
      183 being a surface residue distal from the interface between the large and small
      subunits. This phosphorylation-induced disassembly promotes the formation of
      ordered aggregates around 20 nm in diameter. Similar aggregates of caspase-9 have
      not been previously reported. This two-stage regulatory mechanism for caspase-9
      has likewise not been reported previously but may be conserved across the
      caspases.

PMID- 29352270
TI  - Non-canonical Wnt induces chondrocyte de-differentiation through Frizzled 6 and
      DVL-2/B-raf/CaMKIIalpha/syndecan 4 axis.
AB  - Dysregulation of Wnt signaling has been implicated in developmental defects and
      in the pathogenesis of many diseases such as osteoarthritis; however, the
      underlying mechanisms are poorly understood. Here, we report that non-canonical
      Wnt signaling induced loss of chondrocyte phenotype through activation of Fz
      6/DVL-2/SYND4/CaMKIIalpha/B-raf/ERK1/2 cascade. We show that in response to Wnt
      3a, Frizzled 6 (Fz-6) triggers the docking of CaMKIIalpha to syndecan 4 (SYND4)
      and that of B-raf to DVL-2, leading to the phosphorylation of B-raf by
      CaMKIIalpha and activation of extracellular signal-regulated kinase 1 and 2
      (ERK1/2) signaling, which leads to chondrocyte de-differentiation. We demonstrate
      that CaMKIIalpha associates and phosphorylates B-raf in vitro and in vivo. Our
      study reveals the mechanism by which non-canonical Wnt activates ERK1/2 signaling
      that induces loss of chondrocyte phenotype, and demonstrates a direct functional
      relationship between CaMKIIalpha and B-raf during chondrocyte de-differentiation.
      The identification of Fz-6, SYND4, and B-raf as novel physiological regulators of
      chondrocyte phenotype may provide new potential anti-osteoarthritic targets.

PMID- 29352271
TI  - Sex disparity in cancer: roles of microRNAs and related functional players.
AB  - A sexual dimorphism at the cellular level has been suggested to play a role in
      cancer onset and progression. In particular, very recent studies have unraveled
      striking differences between cells carrying XX or XY chromosomes in terms of
      response to stressful stimuli, indicating the presence of genetic and epigenetic
      differences determining sex-specific metabolic or phenotypic traits. Although
      this field of investigation is still in its infancy, available data suggest a key
      role of sexual chromosomes in determining cell life or death. In particular,
      cells carrying XX chromosomes exhibit a higher adaptive potential and survival
      behavior in response to microenvironmental variations with respect to XY cells.
      Cells from females also appear to be equipped with more efficient epigenetic
      machinery than the male counterpart. In particular, the X chromosome contains an
      unexpected high number of microRNAs (miRs), at present 118, in comparison with
      only two miRs localized on chromosome Y, and an average of 40-50 on the
      autosomes. The regulatory power of these small non-coding RNAs is well
      recognized, as 30-50% of all protein-coding genes are targeted by miRs and their
      role in cell fate has been well demonstrated. In addition, several further
      insights, including DNA methylation patterns that are different in males and
      females, claim for a significant gender disparity in cancer and in the immune
      system activity against tumors. In this brief paper, we analyze the state of the
      art of our knowledge on the implication of miRs encoded on sex chromosomes, and
      their related functional paths, in the regulation of cell homeostasis and depict
      possible perspectives for the epigenetic research in the field.

PMID- 29352273
TI  - Binder-free sheet-type all-solid-state batteries with enhanced rate capabilities
      and high energy densities.
AB  - All-solid-state batteries using inorganic solid electrolytes are considered
      promising energy storage systems because of their safety and long life. Stackable
      and compact sheet-type all-solid-state batteries are urgently needed for
      industrial applications such as smart grids and electric vehicles. A binder is
      usually indispensable to the construction of sheet-type batteries; however, it
      can decrease the power and cycle performance of the battery. Here we report the
      first fabrication of a binder-free sheet-type battery. The key to this
      development is the use of volatile poly(propylene carbonate)-based binders; used
      to fabricate electrodes, solid electrolyte sheets, and a stacked three-layered
      sheet, these binders can also be removed by heat treatment. Binder removal leads
      to enhanced rate capability, excellent cycle stability, and a 2.6-fold increase
      in the cell-based-energy-density over previously reported sheet-type batteries.
      This achievement is the first step towards realizing sheet-type batteries with
      high energy and power density.

PMID- 29352272
TI  - Nuclear p53-mediated repression of autophagy involves PINK1 transcriptional down
      regulation.
AB  - p53 is a transcription factor that is implicated in the control of both apoptotic
      and autophagic cell death. This tumor suppressor elicits both pro-autophagic and
      anti-autophagic phenotypes depending of its intracellular localization. The
      ability of p53 to repress autophagy has been exclusively associated to its
      cytoplasmic localization. Here, we show that transcriptional activity of p53 also
      contributes to autophagy down-regulation. Thus, nuclear p53 controls PINK1, a key
      protein involved in the control of mitophagy, by repressing its promoter
      activity, protein and mRNA levels, ex-vivo and in vivo. We establish that
      deletion of an identified p53 responsive element on PINK1 promoter impacts p53
      mediated PINK1 transcriptional repression and we demonstrate a p53-PINK1 physical
      interaction by chromatin immunoprecipitation. Accordingly, we show that only
      nuclear p53 accounts for its ability to repress PINK1 gene transcription.
      Further, we demonstrate ex-vivo and in vivo that p53 invalidation in human cells
      increases LC3 maturation as well as optineurin and NDP52 autophagy receptors
      expression and down-regulates TIM23, TOM20 and HSP60 mitophagy markers.
      Importantly, this phenotype is mimicked by TP53 invalidation in mice brain.
      Finally, by combining pharmacological and genetic approaches, we show that the
      p53-mediated negative regulation of autophagy is PINK1-dependent. Thus pifithrin
      alpha-mediated blockade of p53 transcriptional activity enhances LC3 maturation
      and reduces p62, TIM23, TOM20 and HSP60 protein levels. This pifithrin-alpha
      associated pro-mitophagy phenotype is fully abolished by PINK1 depletion. This
      data unravels a novel pathway by which nuclear p53 can repress
      autophagy/mitophagy that could underlie important dysfunctions in both
      neurodegenerative and cancer diseases.

PMID- 29352274
TI  - Compliance-Free, Digital SET and Analog RESET Synaptic Characteristics of Sub
      Tantalum Oxide Based Neuromorphic Device.
AB  - A two terminal semiconducting device like a memristor is indispensable to emulate
      the function of synapse in the working memory. The analog switching
      characteristics of memristor play a vital role in the emulation of biological
      synapses. The application of consecutive voltage sweeps or pulses (action
      potentials) changes the conductivity of the memristor which is considered as the
      fundamental cause of the synaptic plasticity. In this study, a neuromorphic
      device using an in-situ growth of sub-tantalum oxide switching layer is
      fabricated, which exhibits the digital SET and analog RESET switching with an
      electroforming process without any compliance current (compliance free). The
      process of electroforming and SET is observed at the positive sweeps of +2.4 V
      and +0.86 V, respectively, while multilevel RESET is observed with the
      consecutive negative sweeps in the range of 0 V to -1.2 V. The movement of oxygen
      vacancies and gradual change in the anatomy of the filament is attributed to
      digital SET and analog RESET switching characteristics. For the Ti/Ta2O3-x/Pt
      neuromorphic device, the Ti top and Pt bottom electrodes are considered as
      counterparts of the pre-synaptic input terminal and a post-synaptic output
      terminal, respectively.

PMID- 29352275
TI  - Dexamethasone induced miR-155 up-regulation in differentiating 3T3-L1
      preadipocytes does not affect adipogenesis.
AB  - Dexamethasone is a synthetic glucocorticoid that is widely used as an adipogenic
      inducer in both murine and human in vitro models. Glucocorticoids have been shown
      to regulate early transcriptional events in adipogenesis. MicroRNAs (miRNAs) have
      been also implicated in the regulation of preadipocyte differentiation; however,
      the effects of glucocorticoids on miRNA expression levels during this process
      have not been studied. In this study we investigated the effects of
      glucocorticoids on the expression levels of miR-155 in differentiating 3T3-L1
      preadipocytes. We found that miR-155 levels were up-regulated (2.4-fold) by
      glucocorticoids in differentiating 3T3-L1 preadipocytes, and this enhancement was
      abolished in the presence of RU486, a glucocorticoid receptor antagonist. In
      contrast, treatment with rosiglitazone, another adipogenic inducer decreased the
      expression levels of miR-155 in these cells. Further, our data show that
      endogenous miR-155 is unlikely to be involved in adipogenesis as we show that
      both dexamethasone and rosiglitazone induced adipogenesis to similar levels.
      Furthermore, using miR-155 inhibitor, we showed that the dexamethasone mediated
      miR-155 enhancement did not alter adipogenesis. Our data show that dexamethasone
      but not rosiglitazone increases miR-155 expression and that the increased
      expression of miR-155 is not involved in the dexamethasone-mediated adipogenesis
      in the 3T3-L1 model.

PMID- 29352276
TI  - Arrhythmogenic drugs can amplify spatial heterogeneities in the electrical
      restitution in perfused guinea-pig heart: An evidence from assessments of
      monophasic action potential durations and JT intervals.
AB  - Non-uniform shortening of the action potential duration (APD90) in different
      myocardial regions upon heart rate acceleration can set abnormal repolarization
      gradients and promote arrhythmia. This study examined whether spatial
      heterogeneities in APD90 restitution can be amplified by drugs with clinically
      proved proarrhythmic potential (dofetilide, quinidine, procainamide, and
      flecainide) and, if so, whether these effects can translate to the appropriate
      changes of the ECG metrics of ventricular repolarization, such as JT intervals.
      In isolated, perfused guinea-pig heart preparations, monophasic action potentials
      and volume-conducted ECG were recorded at progressively increased pacing rates.
      The APD90 measured at distinct ventricular sites, as well as the JTpeak and JTend
      values were plotted as a function of preceding diastolic interval, and the
      maximum slopes of the restitution curves were determined at baseline and upon
      drug administration. Dofetilide, quinidine, and procainamide reverse rate
      dependently prolonged APD90 and steepened the restitution curve, with effects
      being greater at the endocardium than epicardium, and in the right ventricular
      (RV) vs. the left ventricular (LV) chamber. The restitution slope was increased
      to a greater extent for the JTend vs. the JTpeak interval. In contrast,
      flecainide reduced the APD90 restitution slope at LV epicardium without producing
      effect at LV endocardium and RV epicardium, and reduced the JTpeak restitution
      slope without changing the JTend restitution. Nevertheless, with all agents,
      these effects translated to the amplified epicardial-to-endocardial and the LV-to
      RV non-uniformities in APD90 restitution, paralleled by the increased JTend vs.
      JTpeak difference in the restitution slope. In summary, these findings suggest
      that arrhythmic drug profiles are partly attributable to the accentuated regional
      heterogeneities in APD90 restitution, which can be indirectly determined through
      ECG assessments of the JTend vs. JTpeak dynamics at variable pacing rates.

PMID- 29352277
TI  - Influence of early stress on memory reconsolidation: Implications for post
      traumatic stress disorder treatment.
AB  - Post-traumatic stress disorder (PTSD) is a common consequence of exposure to a
      life-threatening event. Currently, pharmacological treatments are limited by high
      rates of relapse, and novel treatment approaches are needed. We have recently
      demonstrated that propranolol, a beta-adrenergic antagonist, inhibited aversive
      memory reconsolidation in animals. Following this, in an open-label study 70% of
      patients with PTSD treated with propranolol during reactivation of traumatic
      memory exhibited full remission. However, the reason why 30% of these patients
      did not respond positively to propranolol treatment is still unclear. One of the
      major candidates as factor of treatment resistance is the patient's early-life
      traumatic history. To test the role of this factor, mice with pre- or postnatal
      stress are being tested in fear conditioning and in a new behavioral task, the
      "city-like", specifically designed as a mouse model of PTSD. After reactivation
      of the traumatic event, mice received propranolol injection to block the
      noradrenergic system during memory reconsolidation. Results show that, in the
      "city-like" test, control mice strongly avoided the shock compartment but also
      the compartments containing cues associated with the electric shocks. Injection
      of propranolol after reactivation greatly reduced the memory of the traumatic
      event, but this effect was not present when mice had received pre- or postnatal
      stress. Moreover, propranolol produced only a very weak effect in the fear
      conditioning test, and never changed the corticosterone level whatever the
      behavioral experiment. Taken together our results suggest that our new
      behavioural paradigm is well adapted to PTSD study in mice, and that early stress
      exposure may have an impact on propranolol PTSD treatment outcome. These data are
      critical to understanding the effect of propranolol treatment, in order to
      improve the therapeutic protocol currently used in humans.

PMID- 29352278
TI  - Factors associated with cervical precancerous lesions among women screened for
      cervical cancer in Addis Ababa, Ethiopia: A case control study.
AB  - BACKGROUND: Cervical cancer is the second most prevalent cancer among women in
      the developing countries including Ethiopia. Precancerous lesions can be
      developed and risk to the development of cervical cancer over time. Early
      identification of the precancerous lesion and its risk factor is paramount in
      preventing cervical cancer. However, the determinants of cervical precancerous
      lesions are not well documented in Ethiopia. Therefore, this study is conducted
      to determine factors associated with cervical precancerous lesion among women
      screened for cervical cancer. METHODS: A hospital-based unmatched case-control
      study was conducted in selected health facilities in Addis Ababa from March to
      April 2016. Data were collected from 114 cases and 229 controls using an
      interviewer-administered questionnaire, entered to Epi Info version 7, and
      exported to SPSS version 20 for analysis. Odds ratios with its 95% confidence
      intervals and two-tailed P-value were calculated. Variables with P-value <= 0.2
      in the bivariate analysis were included in the multivariate logistic regression
      model. RESULTS: Women aged 40-49 years had 2.4-fold higher odds of precancerous
      lesions compared to those aged 30-39 (Adjusted Odds Ratio = 2.4, 95% Confidence
      Interval: 1.27-4.54). Women having history of sexually transmitted infections
      were significantly associated with cervical precancerous lesion compared to their
      counterparts (Adjusted Odds Ratio = 3.20, 95% Confidence Interval: 1.26-8.10).
      Similarly, those women who had two or more lifetime sexual partners (Adjusted
      Odds Ratio = 2.17 95% Confidence Interval: 1.01-4.67), and women whose husbands
      had two or more lifetime sexual partners (Adjusted Odds Ratio = 3.03, 95%
      Confidence Interval: 1.25, 7.33) had higher odds of cervical precancerous
      lesions. CONCLUSIONS: Older age, history of multiple sexual partners and sexual
      transmitted infections were associated with increased risk of precancerous
      lesion. Therefore, women with higher risk of precancerous lesions should be
      encouraged to be screened more frequently for cervical cancer.

PMID- 29352279
TI  - Girls in the boat: Sex differences in rowing performance and participation.
AB  - Men outperform women in many athletic endeavors due to physiological and
      anatomical differences (e.g. larger and faster muscle); however, the observed sex
      differences in elite athletic performance are typically larger than expected, and
      may reflect sex-related differences in opportunity or incentives. As collegiate
      rowing in the United States has been largely incentivized for women over the last
      20 years, but not men, the purpose of this study was to examine sex differences
      in elite rowing performance over that timeframe. Finishing times from grand
      finale races for collegiate championship on-water performances (n = 480) and
      junior indoor performances (n = 1,280) were compared between men and women across
      20 years (1997-2016), weight classes (heavy vs. lightweight) and finishing place.
      Participation of the numbers of men and women rowers were also quantified across
      years. Men were faster than women across all finishing places, weight classes and
      years of competition and performance declined across finishing place for both men
      and women (P<0.001). Interestingly, the reduction in performance time across
      finishing place was greater (P<0.001) for collegiate men compared to women in the
      heavyweight division. This result is opposite to other sports (e.g. running and
      swimming), and to lightweight rowing in this study, which provides women fewer
      incentives than in heavyweight rowing. Correspondingly, participation in
      collegiate rowing has increased by ~113 women per year (P<0.001), with no change
      (P = 0.899) for collegiate men. These results indicate that increased
      participation and incentives within collegiate rowing for women vs. men
      contribute to sex differences in athletic performance.

PMID- 29352280
TI  - Leisure-time physical activity and prevalence of non-communicable pathologies and
      prescription medication in Spain.
AB  - Our aims were to describe physical activity (PA) behaviour in Spain and to
      examine its association with the prevalence of some of the major non-communicable
      diseases and with the use of prescription medication. Individualized secondary
      data retrieved from the 2014 European Health Interview Survey (EHIS) for Spain
      were used to conduct a cross-sectional epidemiological study (n = 18926). PA was
      assessed by two different measures: a specific designed variable for EHIS and a
      leisure time PA frequency-based query of the national survey. Diseases analyzed
      were hypertension, diabetes, hypercholesterolemia, depression and anxiety. The
      use of prescription medication was also included in the study. Weighted
      percentages were computed and contingency tables were calculated to describe PA
      by levels of the traits and sociodemographic characteristics. Chi-square test was
      used to compare percentages between groups and weighted logistic regression
      models were used to assess the relationship between PA and the prevalence of the
      disease. About 73% of the Spanish population performs no PA at all or only
      occasionally during their leisure time, and only one third meets minimum PA
      international guidelines (>= 150min/week). Men are considerably more active than
      women and less PA is observed as the education level decreases and as age
      increases. The risk of the diseases evaluated was up to three times higher among
      inactive individuals. This study provides national population-based estimations
      highlighting the impact of PA in Spain, not only in the prevalence of some of the
      major non-communicable diseases but also in reducing prescription medication, and
      the potential sex and socioeconomic influence.

PMID- 29352281
TI  - Differential DNA methylation and transcription profiles in date palm roots
      exposed to salinity.
AB  - As a salt-adaptive plant, the date palm (Phoenix dactylifera L.) requires a
      suitable mechanism to adapt to the stress of saline soils. There is growing
      evidence that DNA methylation plays an important role in regulating gene
      expression in response to abiotic stresses, including salinity. Thus, the present
      study sought to examine the differential methylation status that occurs in the
      date palm genome when plants are exposed to salinity, and to identify salinity
      responsive genes that are regulated by DNA methylation. To achieve these, whole
      genome bisulfite sequencing (WGBS) was employed and mRNA was sequenced from
      salinity-treated and untreated roots. The WGBS analysis included 324,987,795 and
      317,056,091 total reads of the control and the salinity-treated samples,
      respectively. The analysis covered about 81% of the total genomic DNA with about
      40% of mapping efficiency of the sequenced reads and an average read depth of 17
      fold coverage per DNA strand, and with a bisulfite conversion rate of around 99%.
      The level of methylation within the differentially methylated regions (DMRs) was
      significantly (p < 0.05, FDR <= 0.05) increased in response to salinity
      specifically at the mCHG and mCHH sequence contexts. Consistently, the mass
      spectrometry and the enzyme-linked immunosorbent assay (ELISA) showed that there
      was a significant (p < 0.05) increase in the global DNA methylation in response
      to salinity. mRNA sequencing revealed the presence of 6,405 differentially
      regulated genes with a significant value (p < 0.001, FDR <= 0.05) in response to
      salinity. Integration of high-resolution methylome and transcriptome analyses
      revealed a negative correlation between mCG methylation located within the
      promoters and the gene expression, while a positive correlation was noticed
      between mCHG/mCHH methylation rations and gene expression specifically when
      plants grew under control conditions. Therefore, the methylome and transcriptome
      relationships vary based on the methylated sequence context, the methylated
      region within the gene, the protein-coding ability of the gene, and the salinity
      treatment. These results provide insights into interplay among DNA methylation
      and gene expression, and highlight the effect of salinity on the nature of this
      relationship, which may involve other genetic and epigenetic players under salt
      stress conditions. The results obtained from this project provide the first draft
      map of the differential methylome and transcriptome of date palm when exposed to
      an abiotic stress.

PMID- 29352282
TI  - An energy-efficient failure detector for vehicular cloud computing.
AB  - Failure detectors are one of the fundamental components for maintaining the high
      availability of vehicular cloud computing. In vehicular cloud computing, lots of
      RSUs are deployed along the road to improve the connectivity. Many of them are
      equipped with solar battery due to the unavailability or excess expense of wired
      electrical power. So it is important to reduce the battery consumption of RSU.
      However, the existing failure detection algorithms are not designed to save
      battery consumption RSU. To solve this problem, a new energy-efficient failure
      detector 2E-FD has been proposed specifically for vehicular cloud computing. 2E
      FD does not only provide acceptable failure detection service, but also saves the
      battery consumption of RSU. Through the comparative experiments, the results show
      that our failure detector has better performance in terms of speed, accuracy and
      battery consumption.

PMID- 29352283
TI  - Using a model comparison approach to describe the assembly pathway for histone
      H1.
AB  - Histones H1 or linker histones are highly dynamic proteins that diffuse
      throughout the cell nucleus and associate with chromatin (DNA and associated
      proteins). This binding interaction of histone H1 with the chromatin is thought
      to regulate chromatin organization and DNA accessibility to transcription factors
      and has been proven to involve a kinetic process characterized by a population
      that associates weakly with chromatin and rapidly dissociates and another
      population that resides at a binding site for up to several minutes before
      dissociating. When considering differences between these two classes of
      interactions in a mathematical model for the purpose of describing and
      quantifying the dynamics of histone H1, it becomes apparent that there could be
      several assembly pathways that explain the kinetic data obtained in living cells.
      In this work, we model these different pathways using systems of reaction
      diffusion equations and carry out a model comparison analysis using FRAP
      (fluorescence recovery after photobleaching) experimental data from different
      histone H1 variants to determine the most feasible mechanism to explain histone
      H1 binding to chromatin. The analysis favors four different chromatin assembly
      pathways for histone H1 which share common features and provide meaningful
      biological information on histone H1 dynamics. We show, using perturbation
      analysis, that the explicit consideration of high- and low-affinity associations
      of histone H1 with chromatin in the favored assembly pathways improves the
      interpretation of histone H1 experimental FRAP data. To illustrate the results,
      we use one of the favored models to assess the kinetic changes of histone H1
      after core histone hyperacetylation, and conclude that this post-transcriptional
      modification does not affect significantly the transition of histone H1 from a
      weakly bound state to a tightly bound state.

PMID- 29352284
TI  - Sensitive detection of fluorescence in western blotting by merging images.
AB  - The western blotting technique is widely used to analyze protein expression
      levels and protein molecular weight. The chemiluminescence method is mainly used
      for detection due to its high sensitivity and ease of manipulation, but it is
      unsuitable for detailed analyses because it cannot be used to detect multiple
      proteins simultaneously. Recently, more attention has been paid to the
      fluorescence detection method because it is more quantitative and is suitable for
      the detection of multiple proteins simultaneously. However, fluorescence
      detection can be limited by poor image resolution and low detection sensitivity.
      Here, we describe a method to detect fluorescence in western blots using
      fluorescence microscopy to obtain high-resolution images. In this method, filters
      and fluorescent dyes are optimized to enhance detection sensitivity to a level
      similar to that of the chemiluminescence method.

PMID- 29352285
TI  - Deep neural networks show an equivalent and often superior performance to
      dermatologists in onychomycosis diagnosis: Automatic construction of
      onychomycosis datasets by region-based convolutional deep neural network.
AB  - Although there have been reports of the successful diagnosis of skin disorders
      using deep learning, unrealistically large clinical image datasets are required
      for artificial intelligence (AI) training. We created datasets of standardized
      nail images using a region-based convolutional neural network (R-CNN) trained to
      distinguish the nail from the background. We used R-CNN to generate training
      datasets of 49,567 images, which we then used to fine-tune the ResNet-152 and VGG
      19 models. The validation datasets comprised 100 and 194 images from Inje
      University (B1 and B2 datasets, respectively), 125 images from Hallym University
      (C dataset), and 939 images from Seoul National University (D dataset). The AI
      (ensemble model; ResNet-152 + VGG-19 + feedforward neural networks) results
      showed test sensitivity/specificity/ area under the curve values of (96.0 / 94.7
      / 0.98), (82.7 / 96.7 / 0.95), (92.3 / 79.3 / 0.93), (87.7 / 69.3 / 0.82) for the
      B1, B2, C, and D datasets. With a combination of the B1 and C datasets, the AI
      Youden index was significantly (p = 0.01) higher than that of 42 dermatologists
      doing the same assessment manually. For B1+C and B2+ D dataset combinations,
      almost none of the dermatologists performed as well as the AI. By training with a
      dataset comprising 49,567 images, we achieved a diagnostic accuracy for
      onychomycosis using deep learning that was superior to that of most of the
      dermatologists who participated in this study.

PMID- 29352286
TI  - Echogenic foci with comet-tail artifact in resected thyroid nodules: Not an
      absolute predictor of benign disease.
AB  - The purpose of this study was to evaluate the frequency of echogenic foci with
      comet-tail artifact in histologically proven thyroid nodules, and to determine
      the types of echogenic foci with comet-tail artifact that are associated with
      malignancy. We retrospectively analyzed the sonographic findings of echogenic
      foci with comet-tail artifact, present in thyroid nodules in 63 patients who
      underwent surgery for thyroid nodules at our institution between January 2016 and
      September 2016. The sonographic findings (appearance and background of echogenic
      foci, shape of comet-tail artifact) in benign and malignant nodules were
      compared. Seventy-one (7.4%) nodules with ultrasound finding of echogenic foci
      with comet-tail artifact were encountered in 962 thyroid nodules of 556 patients;
      25 of these were benign, and 46 were malignant. Among the echogenic foci with
      comet-tail artifact categories, those (11/11, 100%) freely distributed in cystic
      components were all in benign nodules, whereas those (48/67, 71.6%) any part of
      echogenic foci or comet-tail artifact associated with solid components, were more
      common in malignant nodules (P < 0.001). There was no statistically significant
      difference in the appearance of echogenic foci and the shape of comet-tail
      between the benign and malignant nodules (P = 0.139, P = 0.626, respectively).
      Echogenic foci with comet-tail artifact freely distributed in cystic component
      may predict a benign nodule; those associated with solid components cannot be
      considered a benign finding.

PMID- 29352287
TI  - IFNgamma inhibits G-CSF induced neutrophil expansion and invasion of the CNS to
      prevent viral encephalitis.
AB  - Emergency hematopoiesis facilitates the rapid expansion of inflammatory immune
      cells in response to infections by pathogens, a process that must be carefully
      regulated to prevent potentially life threatening inflammatory responses. Here,
      we describe a novel regulatory role for the cytokine IFNgamma that is critical
      for preventing fatal encephalitis after viral infection. HSV1 encephalitis (HSE)
      is triggered by the invasion of the brainstem by inflammatory monocytes and
      neutrophils. In mice lacking IFNgamma (GKO), we observed unrestrained increases
      in G-CSF levels but not in GM-CSF or IL-17. This resulted in uncontrolled
      expansion and infiltration of apoptosis-resistant, degranulating neutrophils into
      the brainstem, causing fatal HSE in GKO but not WT mice. Excessive G-CSF in GKO
      mice also induced granulocyte derived suppressor cells, which inhibited T-cell
      proliferation and function, including production of the anti-inflammatory
      cytokine IL-10. Unexpectedly, we found that IFNgamma suppressed G-CSF signaling
      by increasing SOCS3 expression in neutrophils, resulting in apoptosis. Depletion
      of G-CSF, but not GM-CSF, in GKO mice induced neutrophil apoptosis and reinstated
      IL-10 secretion by T cells, which restored their ability to limit innate
      inflammatory responses resulting in protection from HSE. Our studies reveals a
      novel, complex interplay among IFNgamma, G-CSF and IL-10, which highlights the
      opposing roles of G-CSF and IFNgamma in regulation of innate inflammatory
      responses in a murine viral encephalitis model and reveals G-CSF as a potential
      therapeutic target. Thus, the antagonistic G-CSF-IFNgamma interactions emerge as
      a key regulatory node in control of CNS inflammatory responses to virus
      infection.

PMID- 29352288
TI  - Phospholipid scramblase 1 interacts with influenza A virus NP, impairing its
      nuclear import and thereby suppressing virus replication.
AB  - Transcription and replication of the influenza A virus (IAV) genome occur in the
      nucleus of infected cells and are carried out by the viral ribonucleoprotein
      complex (vRNP). As a major component of the vRNP complex, the viral nucleoprotein
      (NP) mediates the nuclear import of the vRNP complex via its nuclear localization
      signals (NLSs). Clearly, an effective way for the host to antagonize IAV
      infection would be by targeting vRNP nuclear import. Here, we identified
      phospholipid scramblase 1 (PLSCR1) as a binding partner of NP by using a yeast
      two-hybrid (Y2H) screen. The interaction between NP and PLSCR1 in mammalian cells
      was demonstrated by using co-immunoprecipitation and pull-down assays. We found
      that the stable overexpression of PLSCR1 suppressed the nuclear import of NP,
      hindered the virus life cycle, and significantly inhibited the replication of
      various influenza subtypes. In contrast, siRNA knockdown or CRISPR/Cas9 knockout
      of PLSCR1 increased virus propagation. Further analysis indicated that the
      inhibitory effect of PLSCR1 on the nuclear import of NP was not caused by
      affecting the phosphorylation status of NP or by stimulating the interferon (IFN)
      pathways. Instead, PLSCR1 was found to form a trimeric complex with NP and
      members of the importin alpha family, which inhibited the incorporation of
      importin beta, a key mediator of the classical nuclear import pathway, into the
      complex, thus impairing the nuclear import of NP and suppressing virus
      replication. Our results demonstrate that PLSCR1 negatively regulates virus
      replication by interacting with NP in the cytoplasm and preventing its nuclear
      import.

PMID- 29352289
TI  - Electroacupuncture at Guanyuan (CV 4), Zusanli (ST 36) and Baihui (DU 20)
      regulate the aging-related changes in gene expression profile of the hippocampus
      in sub-acutely aging rats.
AB  - To investigate the molecular mechanisms of sub-acutely aging and demonstrate the
      effect of electroacupuncture (EA) at the Guanyuan (CV 4), Zusanli (ST 36) and
      Baihui (DU 20) acupoint on the sub-acutely aging brain, cDNA microarrays and
      bioinformatics analyses were carried out. Thirty Sprague-Dawley (SD) male rats
      were selected and randomly divided into three groups: the control group (C), the
      sub-acutely aging model group (M) and the electroacupuncture group (M+EA). Sub
      acutely aging model rats were obtained by D-galactose s.c. injection continuously
      for 40 days. Total RNA was extracted from the hippocampus area of brains in three
      groups for cDNA microarrays. The data of different groups were compared and
      analyzed by differential expression analysis, Gene ontology (GO) term enrichment,
      Kyoto Encyclopedia of Genes Genomes (KEGG) pathway enrichment and quantitative
      real-time PCR. According to the results, 4052 DE genes were identified in our
      study. Among them, there were 3079 differentially expressed (DE) genes between
      group M and group C, and these genes are associated with the aging of rats.
      Moreover, 983 genes were expressed differently in group M+EA compared with group
      M, revealing that points stimuli could regulate gene expression in brain with
      aging. Gene ontology (GO) term enrichment and KEGG enrichment were performed to
      further classify the differential expression genes. Important GO terms and KEGG
      pathways connected with sub-acutely aging EA effects were identified. At last, 3
      significant differentially expressed genes were selected for real-time
      quantitative PCR to clarify the cDNA microarray results. In conclusion, the cDNA
      microarray data first compared and analyzed the differences of gene expression
      profile in the hippocampus of rats in different groups, which contribute to our
      knowledge on the molecular mechanisms of EA towards sub-acutely aging.

PMID- 29352290
TI  - Correction: Association of physical capacity with heart rate variability based on
      a short-duration measurement of resting pulse rate in older adults with obesity.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189150.].

PMID- 29352291
TI  - Correction: Shared acoustic codes underlie emotional communication in music and
      speech-Evidence from deep transfer learning.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179289.].

PMID- 29352293
TI  - Correction: Properties of halogenated and sulfonated porphyrins relevant for the
      selection of photosensitizers in anticancer and antimicrobial therapies.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185984.].

PMID- 29352292
TI  - RNA-Seq of Kaposi's sarcoma reveals alterations in glucose and lipid metabolism.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of Kaposi's
      sarcoma (KS). It is endemic in a number of sub-Saharan African countries with
      infection rate of >50%. The high prevalence of HIV-1 coupled with late
      presentation of advanced cancer staging make KS the leading cancer in the region
      with poor prognosis and high mortality. Disease markers and cellular functions
      associated with KS tumorigenesis remain ill-defined. Several studies have
      attempted to investigate changes of the gene profile with in vitro infection of
      monoculture models, which are not likely to reflect the cellular complexity of
      the in vivo lesion environment. Our approach is to characterize and compare the
      gene expression profile in KS lesions versus non-cancer tissues from the same
      individual. Such comparisons could identify pathways critical for KS formation
      and maintenance. This is the first study that utilized high throughput RNA-seq to
      characterize the viral and cellular transcriptome in tumor and non-cancer
      biopsies of African epidemic KS patients. These patients were treated anti
      retroviral therapy with undetectable HIV-1 plasma viral load. We found remarkable
      variability in the viral transcriptome among these patients, with viral latency
      and immune modulation genes most abundantly expressed. The presence of KSHV also
      significantly affected the cellular transcriptome profile. Specifically, genes
      involved in lipid and glucose metabolism disorder pathways were substantially
      affected. Moreover, infiltration of immune cells into the tumor did not prevent
      KS formation, suggesting some functional deficits of these cells. Lastly, we
      found only minimal overlaps between our in vivo cellular transcriptome dataset
      with those from in vitro studies, reflecting the limitation of in vitro models in
      representing tumor lesions. These findings could lead to the identification of
      diagnostic and therapeutic markers for KS, and will provide bases for further
      mechanistic studies on the functions of both viral and cellular genes that are
      involved.

PMID- 29352294
TI  - Seasonal variation in environmental DNA detection in sediment and water samples.
AB  - The use of aquatic environmental DNA (eDNA) to detect the presence of species
      depends on the seasonal activity of the species in the sampled habitat. eDNA may
      persist in sediments for longer than it does in water, and analysing sediment
      could potentially extend the seasonal window for species assessment. Using the
      great crested newt as a model, we compare how detection probability changes
      across the seasons in eDNA samples collected from both pond water and pond
      sediments. Detection of both aquatic and sedimentary eDNA varied through the
      year, peaking in the summer (July), with its lowest point in the winter
      (January): in all seasons, detection probability of eDNA from water exceeded that
      from sediment. Detection probability of eDNA also varied between study areas, and
      according to great crested newt habitat suitability and sediment type. As aquatic
      and sedimentary eDNA show the same seasonal fluctuations, the patterns observed
      in both sample types likely reflect current or recent presence of the target
      species. However, given the low detection probabilities found in the autumn and
      winter we would not recommend using either aquatic or sedimentary eDNA for year
      round sampling without further refinement and testing of the methods.

PMID- 29352295
TI  - Correction: Stakeholders' views and experiences of care and interventions for
      addressing frailty and pre-frailty: A meta-synthesis of qualitative evidence.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180127.].

PMID- 29352296
TI  - Correction: Right-wing authoritarianism and stereotype-driven expectations
      interact in shaping intergroup trust in one-shot vs multiple-round social
      interactions.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0190142.].

PMID- 29352297
TI  - Correction: Cardiovascular Effect of Incretin-Based Therapy in Patients with Type
      2 Diabetes Mellitus: Systematic Review and Meta-Analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0153502.].

PMID- 29352298
TI  - Hexokinase II may be dispensable for CD4 T cell responses against a virus
      infection.
AB  - Activation of CD4 T cells leads to their metabolic reprogramming which includes
      enhanced glycolysis, catalyzed through hexokinase enzymes. Studies in some
      systems indicate that the HK2 isoform is the most up regulated isoform in
      activated T cells and in this report the relevance of this finding is evaluated
      in an infectious disease model. Genetic ablation of HK2 was achieved in only T
      cells and the outcome was evaluated by measures of T cell function. Our results
      show that CD4 T cells from both HK2 depleted and WT animals displayed similar
      responses to in vitro stimulation and yielded similar levels of Th1, Treg or Th17
      subsets when differentiated in vitro. A modest increase in the levels of
      proliferation was observed in CD4 T cells lacking HK2. Deletion of HK2 led to
      enhanced levels of HK1 indicative of a compensatory mechanism. Finally, CD4 T
      cell mediated immuno-inflammatory responses to a virus infection were similar
      between WT and HK2 KO animals. The observations that the expression of HK2
      appears non-essential for CD4 T cell responses against virus infections is of
      interest since it suggests that targeting HK2 for cancer therapy may not have
      untoward effects on CD4 T cell mediated immune response against virus infections.

PMID- 29352299
TI  - Bunyavirus requirement for endosomal K+ reveals new roles of cellular ion
      channels during infection.
AB  - In order to multiply and cause disease a virus must transport its genome from
      outside the cell into the cytosol, most commonly achieved through the endocytic
      network. Endosomes transport virus particles to specific cellular destinations
      and viruses exploit the changing environment of maturing endocytic vesicles as
      triggers to mediate genome release. Previously we demonstrated that several
      bunyaviruses, which comprise the largest family of negative sense RNA viruses,
      require the activity of cellular potassium (K+) channels to cause productive
      infection. Specifically, we demonstrated a surprising role for K+ channels during
      virus endosomal trafficking. In this study, we have used the prototype
      bunyavirus, Bunyamwera virus (BUNV), as a tool to understand why K+ channels are
      required for progression of these viruses through the endocytic network. We
      report three major findings: First, the production of a dual fluorescently
      labelled bunyavirus to visualize virus trafficking in live cells. Second, we show
      that BUNV traffics through endosomes containing high [K+] and that these K+ ions
      influence the infectivity of virions. Third, we show that K+ channel inhibition
      can alter the distribution of K+ across the endosomal system and arrest virus
      trafficking in endosomes. These data suggest high endosomal [K+] is a critical
      cue that is required for virus infection, and is controlled by cellular K+
      channels resident within the endosome network. This highlights cellular K+
      channels as druggable targets to impede virus entry, infection and disease.

PMID- 29352300
TI  - 5-aminosalicylic acid improves lipid profile in mice fed a high-fat cholesterol
      diet through its dual effects on intestinal PPARgamma and PPARalpha.
AB  - Obesity is associated with a series of metabolic complications, including
      dyslipidemia and insulin resistance (IR) that lack effective therapies. In recent
      years, intestinal inflammation has been suggested to contribute to obesity
      related metabolic syndrome and targeting gut inflammation with 5-ASA improves
      diet induced IR, however, its role in dyslipidemia is unknown and has never been
      explored. In the present study, we reported for the first time that
      administration of 5-ASA for 12 weeks significantly improved lipid profile by
      repressing plasma triglycerides and free cholesterol levels in mice fed high-fat
      cholesterol diet (HFC). In addition, liver lipids were significantly reduced by 5
      ASA treatment in HFC-fed mice. Mechanistically, anti-inflammatory genes
      peroxisome proliferator-activated receptor-gamma (Ppargamma) and M2 marker, such
      as Mrc1 and Ym1, were remarkably upregulated, while pro-inflammation gene
      monocyte chemoattractant protein-1 (Mcp-1) were downregulated in small intestine
      of mice treated by 5-ASA. Further, 5-ASA improved gastrointestinal barrier by
      increasing the expression of the tight junction marker ZO-1. 5-ASA also enhanced
      cholesterol translocation by elevating genes expression of Npc1l1 and Abcg5/8.
      Moreover, mice fed HFC 5-ASA expressed increased Pparalpha in small intestinal
      and its target genes function in lipid oxidation and hydrolysis were remarkable
      elevated. Taken together, we reported a novel role of 5-ASA which may serve as a
      therapy target intestinal inflammation induced dyslipidemia.

PMID- 29352302
TI  - Correction: Identification of soil P fractions that are associated with P loss
      from surface runoff under various cropping systems and fertilizer rates on sloped
      farmland.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179275.].

PMID- 29352301
TI  - Crystal structure of a UDP-GlcNAc epimerase for surface polysaccharide
      biosynthesis in Acinetobacter baumannii.
AB  - With new strains of Acinetobacter baumannii undergoing genomic analysis, it has
      been possible to define regions of genomic plasticity (RGPs), encoding specific
      adaptive elements. For a selected RGP from a community-derived isolate of A.
      baumannii, we outline sequences compatible with biosynthetic machinery of surface
      polysaccharides, specifically enzymes utilized in the dehydration and conversion
      of UDP-N-acetyl-D-glucosamine (UDP-D-GlcNAc). We have determined the crystal
      structure of one of these, the epimerase Ab-WbjB. This dehydratase belongs to the
      'extended' short-chain dehydrogenase/reductase (SDR) family, related in fold to
      previously characterised enzymes CapE and FlaA1. Our 2.65A resolution structure
      of Ab-WbjB shows a hexamer, organised into a trimer of chain pairs, with coenzyme
      NADP+ occupying each chain. Specific active-site interactions between each
      coenzyme and a lysine quaternary group of a neighbouring chain interconnect
      adjacent dimers, so stabilising the hexameric form. We show UDP-GlcNAc to be a
      specific substrate for Ab-WbjB, with binding evident by ITC (Ka = 0.23 MUmol-1).
      The sequence of Ab-WbjB shows variation from the consensus active-site motifs of
      many SDR enzymes, demonstrating a likely catalytic role for a specific threonine
      sidechain (as an alternative to tyrosine) in the canonical active site chemistry
      of these epimerases.

PMID- 29352305
TI  - Correction: Functional implications of hexameric assembly of RraA proteins from
      Vibrio vulnificus.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0190064.].

PMID- 29352304
TI  - Using daily text messages to improve adherence to infant micronutrient powder
      (MNP) packets in rural western China: A cluster-randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of daily text messages as a means to
      improve caregivers' adherence to infant micronutrient powder (MNP) in rural
      Shaanxi Province of China. METHODOLOGY: 638 infants aged 6-11 months in 234
      villages were involved in a cluster-randomized controlled trial (RCT). All
      caregivers were given free infant MNP packets at baseline in April 2013 and the
      follow-up survey was in July 2013. We randomly assigned 318 infants in 117
      villages to treatment group (receiving daily text message) and 320 infants in the
      other 117 villages as control group. RESULTS: On average, daily text messages
      increased the number of MNP packets fed (marginal effect = 4.63; 95% confidence
      interval (CI) = 0.16, 9.10). The text message is more likely to increase the
      consumption of MNP packets if the primary caregiver was the mother (marginal
      effect = 12.19; 95% CI = 0.69, 23.68). Receiving the text message appears to
      significantly increase the likelihood of full adherence when the primary
      caregiver can either check (odds ratio = 2.93; 95% CI = 1.34, 6.40) or knows how
      to send (odds ratio = 3.26; 95% CI = 1.53, 6.97) text messages. CONCLUSION: Daily
      text messages improved the consumption of infant MNP packets. However, the impact
      was not large enough to increase the probability of caregivers being fully
      adherent to the feeding instruction, which is to feed 5-7 packets per week as
      recommended. In addition, when the mother is the caregiver and when the caregiver
      can check or knows how to send text messages there is greater adherence by the
      primary caregivers. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN44149146.

PMID- 29352303
TI  - Perfusion decellularization of a human limb: A novel platform for composite
      tissue engineering and reconstructive surgery.
AB  - Muscle and fasciocutaneous flaps taken from autologous donor sites are currently
      the most utilized approach for trauma repair, accounting annually for 4.5 million
      procedures in the US alone. However, the donor tissue size is limited and the
      complications related to these surgical techniques lead to morbidities, often
      involving the donor sites. Alternatively, recent reports indicated that
      extracellular matrix (ECM) scaffolds boost the regenerative potential of the
      injured site, as shown in a small cohort of volumetric muscle loss patients.
      Perfusion decellularization is a bioengineering technology that allows the
      generation of clinical-scale ECM scaffolds with preserved complex architecture
      and with an intact vascular template, from a variety of donor organs and tissues.
      We recently reported that this technology is amenable to generate full composite
      tissue scaffolds from rat and non-human primate limbs. Translating this platform
      to human extremities could substantially benefit soft tissue and volumetric
      muscle loss patients providing tissue- and species-specific grafts. In this proof
      of-concept study, we show the successful generation a large-scale, acellular
      composite tissue scaffold from a full cadaveric human upper extremity. This
      construct retained its morphological architecture and perfusable vascular
      conduits. Histological and biochemical validation confirmed the successful
      removal of nuclear and cellular components, and highlighted the preservation of
      the native extracellular matrix components. Our results indicate that perfusion
      decellularization can be applied to produce human composite tissue acellular
      scaffolds. With its preserved structure and vascular template, these
      biocompatible constructs, could have significant advantages over the currently
      implanted matrices by means of nutrient distribution, size-scalability and
      immunological response.

PMID- 29352307
TI  - Aerial ULV control of Aedes aegypti with naled (Dibrom) inside simulated rural
      village and urban cryptic habitats.
AB  - We conducted aerial fixed wing ultra low volume (ULV) spray trials with naled to
      investigate penetration of exposed and simulated cryptic habitat within opened
      buildings, partially sealed buildings, and outdoor locations targeting sentinel
      adult Aedes aegypti mosquitoes in north central Florida. Mortality was observed
      in open and closed buildings and outdoors, even in mosquitoes placed in cryptic
      habitats. Observations on the impact of building type, mosquito exposure method
      such as placement in cryptic habitat, and spray nozzle size on mosquito mortality
      are described and analyzed.

PMID- 29352306
TI  - Prognostic and predictive role of EGFR pathway alterations in biliary cancer
      patients treated with chemotherapy and anti-EGFR.
AB  - The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy
      did not improve survival in biliary tract carcinoma (BTC) patients. Multiple
      mechanisms might be involved in the resistance to anti-EGFR. Here, we explored
      the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase
      domain (TKD), and its amplification status. EGFR mutational status of exons 12,
      18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was
      evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH). Kaplan-Meier
      curves were calculated using the log-rank test. Six patients had mutations in
      exon 12 of EGFR ECD and 7 in EGFR TKD. Neither EGFR ECD nor TKD mutations
      affected progression free survival (PFS) or overall survival (OS) in the entire
      population. In the panitumumab plus GEMOX (P-GEMOX) arm, ECD mutated patients had
      a worse OS, while EGFR TKD mutated patients had a trend towards shorter PFS and
      OS. Overall, the presence of mutations in EGFR or in its transducers did not
      affect PFS or OS, while the extrahepatic cholangiocarcinoma (ECC) mutated
      patients had a worse prognosis compared to WT. Nineteen out of 37 tumors were
      EGFR amplified, but the amplification did not correlate with survival. ECC EGFR
      amplified patients had improved OS, whereas the amplification significantly
      correlated with poor PFS (p = 0.03) in gallbladder carcinoma patients. The high
      molecular heterogeneity is a predominant feature of BTC: the alterations found in
      this work seem to have a prognostic impact rather than a predictive role towards
      anti-EGFR therapy.

PMID- 29352308
TI  - High-efficiency production of human serum albumin in the posterior silk glands of
      transgenic silkworms, Bombyx mori L.
AB  - Human serum albumin (HSA) is an important biological preparation with a variety
      of biological functions in clinical applications. In this study, the mRNA of a
      fusion transposase derived from the pESNT-PBase plasmid and a pBHSA plasmid
      containing the HSA gene under the control of a fibroin light chain (FL) promoter
      were co-injected into fertilized eggs. Fifty-six transgenic silkworm pedigrees
      expressing theexogenous recombinant HSA (rHSA) in the posterior silk glands
      (PSGs) with stable inheritance were successfully obtained. The SDS-PAGE and
      Western blot results confirmed that the rHSA was secreted into the transgenic
      silkworm cocoon, and the rHSA could be easily extracted with phosphate-buffered
      saline (PBS). In our research, the isolated highest amount rHSA constituted up to
      29.1% of the total soluble protein of the cocoon shell, indicating that the
      transgenic silkworm produced an average of 17.4 MUg/mg of rHSA in the cocoon
      shell. The production of soluble rHSA in the PSGs by means of generating
      transgenic silkworms is a novel approach, whereby a large amount of virus-free
      and functional HSA can be produced through the simple rearing of silkworms.

PMID- 29352309
TI  - Correction: Early postnatal vocalizations predict sociability and spatial memory
      in C57BL/6J mice: Individual differences in behavioral traits emerge early in
      development.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186798.].

PMID- 29352311
TI  - Decreased alpha-cell mass and early structural alterations of the exocrine
      pancreas in patients with type 1 diabetes: An analysis based on the nPOD
      repository.
AB  - BACKGROUND AND AIMS: Abnormal glucagon secretion and functional alterations of
      the exocrine pancreas have been described in patients with type 1 diabetes (T1D),
      but their respective anatomical substrata have seldom been investigated. Our aim
      was to develop an automated morphometric analysis process to characterize the
      anatomy of alpha-cell and exocrine pancreas in patients with T1D, using the
      publicly available slides of the Network for Pancreatic Organ Donors (nPOD).
      MATERIALS AND METHODS: The ratio of beta- and alpha-cell area to total tissue
      area were quantified in 75 patients with T1D (thereafter patients) and 66 control
      subjects (thereafter controls), on 2 insulin-stained and 4 glucagon-stained
      slides from both the head and the tail of the pancreas. The beta- and alpha-cell
      masses were calculated in the 66 patients and the 50 controls for which the
      pancreas weight was available. Non-exocrine-non-endocrine tissue area (i.e. non
      acinar, non-insular tissue) to total tissue area ratio was evaluated on both
      insulin- and glucagon-stained slides. Results were expressed as mean +/-SD.
      RESULTS: An automated quantification method was set up using the R software and
      was validated by quantification of beta-cell mass, a well characterized
      parameter. beta-cell mass was 29.6+/-112 mg in patients and 628 +/-717 mg in
      controls (p<0.0001). alpha-cell mass was 181+/-176 mg in patients and 349 +/
      241mg in controls (p<0.0001). Non-exocrine-non-endocrine area to total tissue
      area ratio was 39+/-9% in patients and 29+/- 10% in controls (p<0.0001) and
      increased with age in both groups, with no correlation with diabetes duration in
      patients. CONCLUSION: The absolute alpha-cell mass was lower in patients compared
      to controls, in proportion to the decrease in pancreas weight observed in
      patients. Non-exocrine-non-endocrine area to total tissue area ratio increased
      with age in both groups but was higher in patients at all ages.

PMID- 29352310
TI  - Leishmania proteophosphoglycans regurgitated from infected sand flies accelerate
      dermal wound repair and exacerbate leishmaniasis via insulin-like growth factor 1
      dependent signalling.
AB  - Leishmania parasites are transmitted to vertebrate hosts by female phlebotomine
      sand flies as they bloodfeed by lacerating the upper capillaries of the dermis
      with their barbed mouthparts. In the sand fly midgut secreted
      proteophosphoglycans from Leishmania form a biological plug known as the
      promastigote secretory gel (PSG), which blocks the gut and facilitates the
      regurgitation of infective parasites. The interaction between the wound created
      by the sand fly bite and PSG is not known. Here we nanoinjected a sand fly
      egested dose of PSG into BALB/c mouse skin that lead to the differential
      expression of 7,907 transcripts. These transcripts were transiently up-regulated
      during the first 6 hours post-wound and enriched for pathways involved in
      inflammation, cell proliferation, fibrosis, epithelial cell differentiation and
      wound remodelling. We found that PSG significantly accelerated wound healing in
      vitro and in mice; which was associated with an early up-regulation of
      transcripts involved in inflammation (IL-1beta, IL-6, IL-10, TNFalpha) and
      inflammatory cell recruitment (CCL2, CCL3, CCL4, CXCL2), followed 6 days later by
      enhanced expression of transcripts associated with epithelial cell proliferation,
      fibroplasia and fibrosis (FGFR2, EGF, EGFR, IGF1). Dermal expression of IGF1 was
      enhanced following an infected sand fly bite and was acutely responsive to the
      deposition of PSG but not the inoculation of parasites or sand fly saliva.
      Antibody blockade of IGF1 ablated the gel's ability to promote wound closure in
      mouse ears and significantly reduced the virulence of Leishmania mexicana
      infection delivered by an individual sand fly bite. Dermal macrophages recruited
      to air-pouches on the backs of mice revealed that IGF1 was pivotal to the PSG's
      ability to promote macrophage alternative activation and Leishmania infection.
      Our data demonstrate that through the regurgitation of PSG Leishmania exploit the
      wound healing response of the host to the vector bite by promoting the action of
      IGF1 to drive the alternative activation of macrophages.

PMID- 29352313
TI  - Correction: Timing and rate of spheno-occipital synchondrosis closure and its
      relationship to puberty.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183305.].

PMID- 29352312
TI  - A role for domain I of the hepatitis C virus NS5A protein in virus assembly.
AB  - The NS5A protein of hepatitis C virus (HCV) plays roles in both virus genome
      replication and assembly. NS5A comprises three domains, of these domain I is
      believed to be involved exclusively in genome replication. In contrast, domains
      II and III are required for the production of infectious virus particles and are
      largely dispensable for genome replication. Domain I is highly conserved between
      HCV and related hepaciviruses, and is highly structured, exhibiting different
      dimeric conformations. To investigate the functions of domain I in more detail,
      we conducted a mutagenic study of 12 absolutely conserved and surface-exposed
      residues within the context of a JFH-1-derived sub-genomic replicon and
      infectious virus. Whilst most of these abrogated genome replication, three
      mutants (P35A, V67A and P145A) retained the ability to replicate but showed
      defects in virus assembly. P35A exhibited a modest reduction in infectivity,
      however V67A and P145A produced no infectious virus. Using a combination of
      density gradient fractionation, biochemical analysis and high resolution confocal
      microscopy we demonstrate that V67A and P145A disrupted the localisation of NS5A
      to lipid droplets. In addition, the localisation and size of lipid droplets in
      cells infected with these two mutants were perturbed compared to wildtype HCV.
      Biophysical analysis revealed that V67A and P145A abrogated the ability of
      purified domain I to dimerize and resulted in an increased affinity of binding to
      HCV 3'UTR RNA. Taken together, we propose that domain I of NS5A plays multiple
      roles in assembly, binding nascent genomic RNA and transporting it to lipid
      droplets where it is transferred to Core. Domain I also contributes to a change
      in lipid droplet morphology, increasing their size. This study reveals novel
      functions of NS5A domain I in assembly of infectious HCV and provides new
      perspectives on the virus lifecycle.

PMID- 29352314
TI  - Proactive vs. reactive car driving: EEG evidence for different driving strategies
      of older drivers.
AB  - Aging is associated with a large heterogeneity in the extent of age-related
      changes in sensory, motor, and cognitive functions. All these functions can
      influence the performance in complex tasks like car driving. The present study
      aims to identify potential differences in underlying cognitive processes that may
      explain inter-individual variability in driving performance. Younger and older
      participants performed a one-hour monotonous driving task in a driving simulator
      under varying crosswind conditions, while behavioral and electrophysiological
      data were recorded. Overall, younger and older drivers showed comparable driving
      performance (lane keeping). However, there was a large difference in driving lane
      variability within the older group. Dividing the older group in two subgroups
      with low vs. high driving lane variability revealed differences between the two
      groups in electrophysiological correlates of mental workload, consumption of
      mental resources, and activation and sustaining of attention: Older drivers with
      high driving lane variability showed higher frontal Alpha and Theta activity than
      older drivers with low driving lane variability and-with increasing crosswind-a
      more pronounced decrease in Beta activity. These results suggest differences in
      driving strategies of older and younger drivers, with the older drivers using
      either a rather proactive and alert driving strategy (indicated by low driving
      lane variability and lower Alpha and Beta activity), or a rather reactive
      strategy (indicated by high driving lane variability and higher Alpha activity).

PMID- 29352315
TI  - Correction: Musicians have better memory than nonmusicians: A meta-analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186773.].

PMID- 29352316
TI  - KANSL1 variation is not a major contributing factor in self-limited focal
      epilepsy syndromes of childhood.
AB  - BACKGROUND: KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS),
      characterized by dysmorphic features and intellectual disability; amiable
      personality, congenital malformations and seizures also commonly occur. The
      epilepsy phenotypic spectrum in KdVS is broad, but most individuals have focal
      seizures with some having a phenotype resembling the self-limited focal
      epilepsies of childhood (SFEC). We hypothesized that variants in KANSL1
      contribute to pathogenesis of SFEC. MATERIALS AND METHODS: We screened KANSL1 for
      single nucleotide variants in 90 patients with SFEC. We then screened a cohort of
      208 patients with two specific SFEC syndromes, childhood epilepsy with
      centrotemporal spikes (CECTS) and atypical childhood epilepsy with centrotemporal
      spikes (ACECTS) for KANSL1 variants. The second cohort was also used to evaluate
      minor allelic variants that appeared overrepresented in the initial cohort.
      RESULTS: One variant, p.Lys104Thr, was predicted damaging and appeared
      overrepresented in our 90-patient cohort compared to Genome Aggregation Database
      (gnomAD) allele frequency (0.217 to 0.116, with no homozygotes in gnomAD).
      However, there was no difference in p.Lys104Thr allele frequency in the follow-up
      CECTS/ACECTS cohort and controls. Four rare KANSL1 variants of uncertain
      significance were identified in the CECTS/ACECTS cohort. DISCUSSION: Our data do
      not support a major role for KANSL1 variants in pathogenesis of SFEC.

PMID- 29352317
TI  - Optic flow detection is not influenced by visual-vestibular congruency.
AB  - Optic flow patterns generated by self-motion relative to the stationary
      environment result in congruent visual-vestibular self-motion signals.
      Incongruent signals can arise due to object motion, vestibular dysfunction, or
      artificial stimulation, which are less common. Hence, we are predominantly
      exposed to congruent rather than incongruent visual-vestibular stimulation. If
      the brain takes advantage of this probabilistic association, we expect observers
      to be more sensitive to visual optic flow that is congruent with ongoing
      vestibular stimulation. We tested this expectation by measuring the motion
      coherence threshold, which is the percentage of signal versus noise dots,
      necessary to detect an optic flow pattern. Observers seated on a hexapod motion
      platform in front of a screen experienced two sequential intervals. One interval
      contained optic flow with a given motion coherence and the other contained noise
      dots only. Observers had to indicate which interval contained the optic flow
      pattern. The motion coherence threshold was measured for detection of laminar and
      radial optic flow during leftward/rightward and fore/aft linear self-motion,
      respectively. We observed no dependence of coherence thresholds on vestibular
      congruency for either radial or laminar optic flow. Prior studies using similar
      methods reported both decreases and increases in coherence thresholds in response
      to congruent vestibular stimulation; our results do not confirm either of these
      prior reports. While methodological differences may explain the diversity of
      results, another possibility is that motion coherence thresholds are mediated by
      neural populations that are either not modulated by vestibular stimulation or
      that are modulated in a manner that does not depend on congruency.

PMID- 29352318
TI  - Temozolomide-induced increase of tumorigenicity can be diminished by targeting of
      mitochondria in in vitro models of patient individual glioblastoma.
AB  - Glioblastoma multiforme (GBM) is a highly heterogeneous and aggressive brain
      tumor with a dismal prognosis. Development of resistance towards cytostatic drugs
      like the GBM standard drug temozolomide is a severe problem in GBM treatment. One
      potential source of GBM relapse could be so called cancer stem like cells (CSCs).
      These represent an undifferentiated subpopulation of cells with high potential
      for tumor initiation. Furthermore, it has been shown that differentiated GBM
      cells can regain CSC properties when exposed to continuous temozolomide treatment
      in vitro. In this study, treatment of several primary GBM cell lines with
      clinically relevant doses of temozolomide increased their tumorigenicity as
      determined by colony formation assays in soft agar. Increased tumorigenicity is a
      known property of CSCs. Hence, therapy options that specifically target CSCs are
      under investigation. CSCs appear to be particularly dependent on mitochondria
      biogenesis which may represent a useful target for CSC elimination. Toxicity
      towards mitochondria is a known side effect of several antibiotics. Thus,
      addition of antibiotics like doxycycline may represent a useful tool to inhibit
      CSCs in GBM. Here, we show that combining temozolomide treatment of primary GBM
      cells with doxycycline could counteract the increase of tumorigenicity induced by
      temozolomide treatment.

PMID- 29352319
TI  - Activation of PI3K, Akt, and ERK during early rotavirus infection leads to V
      ATPase-dependent endosomal acidification required for uncoating.
AB  - The cellular PI3K/Akt and/or MEK/ERK signaling pathways mediate the entry process
      or endosomal acidification during infection of many viruses. However, their roles
      in the early infection events of group A rotaviruses (RVAs) have remained
      elusive. Here, we show that late-penetration (L-P) human DS-1 and bovine NCDV RVA
      strains stimulate these signaling pathways very early in the infection.
      Inhibition of both signaling pathways significantly reduced production of viral
      progeny due to blockage of virus particles in the late endosome, indicating that
      neither of the two signaling pathways is involved in virus trafficking. However,
      immunoprecipitation assays using antibodies specific for pPI3K, pAkt, pERK and
      the subunit E of the V-ATPase co-immunoprecipitated the V-ATPase in complex with
      pPI3K, pAkt, and pERK. Moreover, Duolink proximity ligation assay revealed direct
      association of the subunit E of the V-ATPase with the molecules pPI3K, pAkt, and
      pERK, indicating that both signaling pathways are involved in V-ATPase-dependent
      endosomal acidification. Acidic replenishment of the medium restored uncoating of
      the RVA strains in cells pretreated with inhibitors specific for both signaling
      pathways, confirming the above results. Isolated components of the outer capsid
      proteins, expressed as VP4-VP8* and VP4-VP5* domains, and VP7, activated the
      PI3K/Akt and MEK/ERK pathways. Furthermore, psoralen-UV-inactivated RVA and CsCl
      purified RVA triple-layered particles triggered activation of the PI3K/Akt and
      MEK/ERK pathways, confirming the above results. Our data demonstrate that
      multistep binding of outer capsid proteins of L-P RVA strains with cell surface
      receptors phosphorylates PI3K, Akt, and ERK, which in turn directly interact with
      the subunit E of the V-ATPase to acidify the late endosome for uncoating of RVAs.
      This study provides a better understanding of the RVA-host interaction during
      viral uncoating, which is of importance for the development of strategies aiming
      at controlling or preventing RVA infections.

PMID- 29352320
TI  - High-level production and purification in a functional state of an extrasynaptic
      gamma-aminobutyric acid type A receptor containing alpha4beta3delta subunits.
AB  - The inhibitory gamma-aminobutyric acid type A receptors are implicated in
      numerous physiological processes, including cognition and inhibition of
      neurotransmission, rendering them important molecular targets for many classes of
      drugs. Functionally, the entire GABAAR family of receptors can be subdivided into
      phasic, fast acting synaptic receptors, composed of alpha-, beta- and gamma
      subunits, and tonic extrasynaptic receptors, many of which contain the delta
      subunit in addition to alpha- and beta-subunits. Whereas the subunit arrangement
      of the former group is agreed upon, that of the alphabetadelta GABAARs remains
      unresolved by electrophysiological and pharmacological research. To resolve such
      issues will require biophysical techniques that demand quantities of receptor
      that have been previously unavailable. Therefore, we have engineered a stable
      cell line with tetracycline inducible expression of human alpha4-, beta3- and N
      terminally Flag-tagged delta-subunits. This cell line achieved a specific
      activity between 15 and 20 pmol [3H]muscimol sites/mg of membrane protein, making
      it possible to obtain 1 nmole of purified alpha4beta3delta GABAAR from sixty 15
      cm culture dishes. When induced, these cells exhibited agonist-induced currents
      with characteristics comparable to those previously reported for this receptor
      and a pharmacology that included strong modulation by etomidate and the delta
      subunit-specific ligand, DS2. Immunoaffinity purification and reconstitution in
      CHAPS/asolectin micelles resulted in the retention of equilibrium allosteric
      interactions between the separate agonist, anesthetic and DS2 sites. Moreover,
      all three subunits retained glycosylation. The establishment of this well
      characterized cell line will allow molecular level studies of tonic receptors to
      be undertaken.

PMID- 29352321
TI  - Inflammatory-linked changes in CpG island methylation of three opioid peptide
      genes in a rat model for pain.
AB  - Expression of the opioid peptide genes proopiomelanocortin (Pomc), proenkephalin
      (Penk), and prodynorphin (Pdyn), in immune cells plays a key role in endogenous
      pain control. In a rat model of painful unilateral paw inflammation, we isolated
      cells from popliteal lymph nodes and evaluated the role of CpG island C5
      methylation on the transcriptional activation of those genes. Using methylated
      DNA immunoprecipitation, we sorted gDNA into methylated (me) and non-me fractions
      and then determined the CpG island methylation status of each fraction via
      quantitative Real Time-PCR (qRT-PCR). In silico analysis by MethPrimer software
      identified one CpG island in Pdyn and three each in Pomc and Penk. No substantial
      changes in C5-methylation of any gene were observed. In conclusion, the CpG
      island methylation status does not seem to be a key regulator of opioid gene
      activation in immune cells during peripheral tissue inflammation.

PMID- 29352322
TI  - qPortal: A platform for data-driven biomedical research.
AB  - Modern biomedical research aims at drawing biological conclusions from large,
      highly complex biological datasets. It has become common practice to make
      extensive use of high-throughput technologies that produce big amounts of
      heterogeneous data. In addition to the ever-improving accuracy, methods are
      getting faster and cheaper, resulting in a steadily increasing need for scalable
      data management and easily accessible means of analysis. We present qPortal, a
      platform providing users with an intuitive way to manage and analyze quantitative
      biological data. The backend leverages a variety of concepts and technologies,
      such as relational databases, data stores, data models and means of data
      transfer, as well as front-end solutions to give users access to data management
      and easy-to-use analysis options. Users are empowered to conduct their
      experiments from the experimental design to the visualization of their results
      through the platform. Here, we illustrate the feature-rich portal by simulating a
      biomedical study based on publically available data. We demonstrate the
      software's strength in supporting the entire project life cycle. The software
      supports the project design and registration, empowers users to do all-digital
      project management and finally provides means to perform analysis. We compare our
      approach to Galaxy, one of the most widely used scientific workflow and analysis
      platforms in computational biology. Application of both systems to a small case
      study shows the differences between a data-driven approach (qPortal) and a
      workflow-driven approach (Galaxy). qPortal, a one-stop-shop solution for
      biomedical projects offers up-to-date analysis pipelines, quality control
      workflows, and visualization tools. Through intensive user interactions,
      appropriate data models have been developed. These models build the foundation of
      our biological data management system and provide possibilities to annotate data,
      query metadata for statistics and future re-analysis on high-performance
      computing systems via coupling of workflow management systems. Integration of
      project and data management as well as workflow resources in one place present
      clear advantages over existing solutions.

PMID- 29352323
TI  - Identification of a molecular marker tightly linked to bacterial wilt resistance
      in tomato by genome-wide SNP analysis.
AB  - KEY MESSAGE: Genotyping of disease resistance to bacterial wilt in tomato by a
      genome-wide SNP analysis Bacterial wilt caused by Ralstonia pseudosolanacearum is
      one of the destructive diseases in tomato. The previous studies have identified
      Bwr-6 (chromosome 6) and Bwr-12 (chromosome 12) loci as the major quantitative
      trait loci (QTLs) contributing to resistance against bacterial wilt in tomato
      cultivar 'Hawaii7996'. However, the genetic identities of two QTLs have not been
      uncovered yet. In this study, using whole-genome resequencing, we analyzed genome
      wide single-nucleotide polymorphisms (SNPs) that can distinguish a resistant
      group, including seven tomato varieties resistant to bacterial wilt, from a
      susceptible group, including two susceptible to the same disease. In total, 5259
      non-synonymous SNPs were found between the two groups. Among them, only 265 SNPs
      were located in the coding DNA sequences, and the majority of these SNPs were
      located on chromosomes 6 and 12. The genes that both carry SNP(s) and are near
      Bwr-6 and Bwr-12 were selected. In particular, four genes in chromosome 12 encode
      putative leucine-rich repeat (LRR) receptor-like proteins. SNPs within these four
      genes were used to develop SNP markers, and each SNP marker was validated by a
      high-resolution melting method. Consequently, one SNP marker, including a
      functional SNP in a gene, Solyc12g009690.1, could efficiently distinguish tomato
      varieties resistant to bacterial wilt from susceptible varieties. These results
      indicate that Solyc12g009690.1, the gene encoding a putative LRR receptor-like
      protein, might be tightly linked to Bwr-12, and the SNP marker developed in this
      study will be useful for selection of tomato cultivars resistant to bacterial
      wilt.

PMID- 29352325
TI  - Obesity was associated with worse neurological outcome among Japanese patients
      with out-of-hospital cardiac arrest.

PMID- 29352324
TI  - Efficient genome-wide genotyping strategies and data integration in crop plants.
AB  - KEY MESSAGE: Next-generation sequencing (NGS) has revolutionized plant and animal
      research by providing powerful genotyping methods. This review describes and
      discusses the advantages, challenges and, most importantly, solutions to
      facilitate data processing, the handling of missing data, and cross-platform data
      integration. Next-generation sequencing technologies provide powerful and
      flexible genotyping methods to plant breeders and researchers. These methods
      offer a wide range of applications from genome-wide analysis to routine screening
      with a high level of accuracy and reproducibility. Furthermore, they provide a
      straightforward workflow to identify, validate, and screen genetic variants in a
      short time with a low cost. NGS-based genotyping methods include whole-genome re
      sequencing, SNP arrays, and reduced representation sequencing, which are widely
      applied in crops. The main challenges facing breeders and geneticists today is
      how to choose an appropriate genotyping method and how to integrate genotyping
      data sets obtained from various sources. Here, we review and discuss the
      advantages and challenges of several NGS methods for genome-wide genetic marker
      development and genotyping in crop plants. We also discuss how imputation methods
      can be used to both fill in missing data in genotypic data sets and to integrate
      data sets obtained using different genotyping tools. It is our hope that this
      synthetic view of genotyping methods will help geneticists and breeders to
      integrate these NGS-based methods in crop plant breeding and research.

PMID- 29352326
TI  - Noninvasive pulse contour analysis for determination of cardiac output in
      patients with chronic heart failure.
AB  - BACKGROUND: Determination of cardiac output (CO) is essential in diagnosis and
      management of heart failure (HF). The gold standard to obtain CO is invasive
      assessment via thermodilution (TD). Noninvasive pulse contour analysis (NPCA) is
      supposed as a new method of CO determination. However, a validation of this
      method in HF is pending and performed in the present study. METHODS: Patients
      with chronic-stable HF and reduced left ventricular ejection fraction (LVEF <=
      45%; HF-REF) underwent right heart catheterization including TD. NPCA using the
      CNAP Monitor (V5.2.14, CNSystems Medizintechnik AG) was performed simultaneously.
      Three standardized TD measurements were compared with simultaneous auto
      calibrated NPCA CO measurements. RESULTS: In total, 84 consecutive HF-REF
      patients were enrolled prospectively in this study. In 4 patients (5%), TD was
      not successful and for 22 patients (26%, 18 with left ventricular assist device),
      no NPCA signal could be obtained. For the remaining 58 patients, Bland-Altman
      analysis revealed a mean bias of + 1.92 L/min (limits of agreement +/- 2.28
      L/min, percentage error 47.4%) for CO. With decreasing cardiac index, as
      determined by the gold standard of TD, there was an increasing gap between CO
      values obtained by TD and NPCA (r = - 0.75, p < 0.001), resulting in a systematic
      overestimation of CO in more severe HF. TD-CI classified 52 (90%) patients to
      have a reduced CI (< 2.5 L/min/m2), while NPCA documented a reduced CI in 18
      patients (31%) only. CONCLUSIONS: In HF-REF patients, auto-calibrated NPCA
      systematically overestimates CO with decrease in cardiac function. Therefore, to
      date, NPCA cannot be recommended in this cohort.

PMID- 29352327
TI  - LIMK/cofilin pathway and Slingshot are implicated in human colorectal cancer
      progression and chemoresistance.
AB  - Cofilin phospho-regulation is important for actin filament turnover and is
      implicated in cancer. Phosphorylation of cofilin is mediated by LIM kinases
      (LIMKs) and dephosphorylation by Slingshot phosphatases (SSH). LIMKs and SSH
      promote cancer cell invasion and metastasis and represent novel anti-cancer
      targets. However, little is known regarding LIMK/cofilin and SSH in human
      colorectal cancer (CRC). In this study, we aimed to address their expression and
      significance in human CRC. We evaluated expression of non-phosphorylated (active)
      and phosphorylated cofilin, LIMK1, LIMK2, and SSH1 by immunohistochemistry in 143
      human CRC samples in relation to clinicopathologic parameters, response of
      metastatic disease to chemotherapy, and epithelial-mesenchymal transition (EMT)
      markers beta-catenin, E-cadherin, and ZEB. We show that active cofilin, LIMK1,
      LIMK2, and SSH1 are overexpressed in human CRC and are associated with tumor
      progression parameters. SSH1 is an independent predictor of lymph node metastasis
      by multivariate analysis. LIMK1 and SSH1 expression is also higher in non
      responders to chemotherapy, and SSH1 is shown by multivariate analysis to
      independently predict response of metastatic disease to chemotherapy. Active
      cofilin, LIMK1, LIMK2, and SSH1 also correlated with the EMT markers examined. In
      addition, immunofluorescence analysis showed increased expression of active
      cofilin, LIMK1, LIMK2, and SSH1 in HT29 colon cancer cells resistant to 5
      fluorouracil compared to parental HT29 cells. Our results suggest that F-actin
      regulators LIMK/cofilin pathway and SSH1 are associated with CRC progression and
      chemoresistance representing promising tumor biomarkers and therapeutic targets
      in CRC.

PMID- 29352328
TI  - Attenuation of serotonin-induced itch by sumatriptan: possible involvement of
      endogenous opioids.
AB  - Serotonin (5-hydroxytryptamine or 5-HT) is a neurotransmitter in itch and
      impaired serotonin signaling has been linked to a variety of itch conditions.
      Intradermal injection of 5-HT induces scratching behavior in mice through
      stimulation of 5-HT receptors. Previous studies have demonstrated that selective
      5-HT1B/1D receptors agonists, including sumatriptan, inhibits neurotransmission.
      We have also reported that sumatriptan suppresses chloroquine-induced itch.
      Therefore, we investigated if sumatriptan has inhibitory effects on serotonin
      induced itch in mice. Here, we show that intradermal and intraperitoneal
      administration of sumatriptan significantly reduce 5-HT-induced scratching
      behavior in mice. While intradermal injection of GR-127935, a selective 5-HT1B/1D
      receptors antagonist, reverses the anti-pruritic effects of sumatriptan. In
      addition, we show that intradermal and intraperitoneal naltrexone (NTX), a non
      specific opioid receptor antagonist, and methylnaltrexone (MNTX), a peripherally
      acting opioid receptor antagonist, significantly decrease the 5-HT-induced
      scratching behavior. Additionally, combined treatment with sub-effective doses of
      sumatriptan and an opioid receptor antagonist, naltrexone, decreases 5-HT-evoked
      scratching responses. We conclude that sumatriptan inhibits 5-HT-induced itch by
      activating the peripheral 5-HT1B/1D receptors. Moreover, peripheral opioid
      receptors have a role in serotonin-induced itch, and anti-pruritic effects of
      sumatriptan seem to involve the opioid system. These data suggest that 5-HT1B/1D
      receptors agonists maybe useful to treat a variety of pathologic itch conditions
      with impaired serotonergic system.

PMID- 29352329
TI  - The Advantages of Bilateral Osteotomy Over Unilateral Osteotomy for Osteoporotic
      Bone Healing.
AB  - Most models of osteoporotic bone fractures are performed unilaterally (UL). We
      investigated healing of tibia osteotomy performed either UL or bilaterally (BL)
      in ovariectomized rats. Behavior of animals and muscle structure were assessed.
      Three-month-old female Sprague-Dawley rats were ovariectomized (n = 32). After 10
      weeks, half the rats underwent UL osteotomy of tibia metaphysis (right limb) with
      plate osteosynthesis. The other rats were osteotomized BL. Half of the rats in
      each group received either standard pain treatment with carprofen (5 mg/kg body
      weight (BW), 1x/day for 2 days) or carprofen and buprenorphine (5 mg/kg BW,
      1x/day and 0.03 mg/kg BW, 2x/day for 5 days) after osteotomy. The UL rats started
      to load the injured limb from day 27 +/- 9; BL rats did this from day 4 +/- 4
      onward. The UL rats more frequently loaded only one hind limb; BL rats more often
      loaded both hind limbs. Osteotomy was not bridged in 20% of UL rats and in 4% of
      BL rats. Callus volume and bone volume fraction were lower in UL group. Weight
      and fiber size of UL-intact limb muscles were enhanced, compared to the
      osteotomized limb and those in BL group. Most of the other parameters which
      assess physiology, activity, body posture, head, or coat were not different. The
      effect of two pain therapies was not significant on any variable studied. Welfare
      of the animals was acceptable in all rats. In UL rats, bone healing was delayed.
      The more advanced healing in BL rats suggested a positive effect of earlier
      loading. In studies on bone healing, it is advisable to perform BL osteotomy.

PMID- 29352331
TI  - Transanal total mesorectal excision: is it necessary in the era of robots?
AB  - Transanal total mesorectal excision (taTME) has been proposed to overcome the
      limitations of laparoscopic TME. The robotic surgical platform has already
      established its benefits in providing superior ergonomics, and the purported
      advantages of taTME may play less important a role in the era of robots.

PMID- 29352330
TI  - Relationship between power-duration parameters and mechanical and anthropometric
      properties of the thigh in elite cyclists.
AB  - PURPOSE: The curvature constant (W') and asymptote (critical power; CP) of the
      power-duration relationship are important parameters for explaining cycling
      performance. Short-duration endurance cycling events rely more heavily on the W';
      however, the full mechanistic underpinning of this parameter is yet to be
      determined. Evidence suggests both muscle volume and muscle strength may
      contribute to the magnitude of W'. Therefore, the present study investigated the
      relationship between power-duration parameters (CP and W') and (1) anthropometric
      and (2) mechanical properties of thigh muscles in a sample of elite cyclists.
      METHODS: Eleven elite male cyclists had gross thigh volume (TVOL), quadriceps
      muscle volume (QVOL), vastus lateralis (VL) muscle pennation angle (PA) and VL
      muscle thickness (MT) measured. Additionally, maximum torque production of the
      knee extensors (FMAX) was assessed. The relationship between these anthropometric
      and mechanical measures and both the CP and W' were determined. RESULTS: W'
      showed a very strong positive and significant relationship with FMAX (r = 0.87, p
      < 0.001) and a large positive and significant relationship with TVOL (r = 0.60, p
      =  0.05). No other anthropometric characteristics were related to the W'. The CP
      was not associated with any mechanical or anthropometric parameter. CONCLUSION:
      In addition to muscle size, the maximal evocable force of a muscle (group)
      appears to be linked to the magnitude of the W' in elite cyclists.

PMID- 29352332
TI  - Effects of continuous or intermittent low-magnitude high-frequency vibration on
      fracture healing in sheep.
AB  - PURPOSE: Vibration therapy has been shown to improve fracture healing. In this
      study, we investigated the effects of continuous or different intermittent
      vibration regimens on fracture healing in sheep models on the basis of
      radiographs, mechanical, and biochemical testing. METHODS: The 63 right-hind
      metatarsals from 63 sheep (12-month-old) were osteotomized; followed by surgical
      fixation with a steel plate. Two weeks after the surgery, the sheep with right
      hind metatarsal fractures were randomly divided into seven groups (n=9/group):
      control (no vibration treated), continuous vibration (CV), one, three, five,
      seven and 14-day intermittent vibration (named IV-1, -3, -5, -7, and -14,
      respectively) groups, which represented a cycle of the successive n-day vibration
      and successive n-day break. Vibration stimulation (F=35 Hz, a=0.25 g) lasted 15
      minutes each treatment. After eight weeks with/without vibration treatment, the
      sheep were euthanized with intravenous anesthetic. The callus formation,
      mechanical properties, and biochemical compositions of fracture metatarsals were
      analyzed. RESULTS: In CV and IV-7 groups, X-ray images showed an increased callus
      volume around the fracture area. The bone elastic modulus and the concentrations
      of Ca, P, and Ca/P ratio of the area at 15 and 25 mm away from the fracture
      centerline were higher in CV and IV-7 groups compared with the other groups.
      CONCLUSIONS: Our results demonstrate that both CV and IV-7 vibration patterns
      showed better improvement of fracture healing.

PMID- 29352333
TI  - Long-term results of custom cementless-stem total hip arthroplasty performed in
      hip fusion.
AB  - INTRODUCTION: Due to complex anatomical considerations, results of cementless
      stem total hip arthroplasty (THA) in hip fusion remain controversial compared
      with conventional THA. We therefore aimed to analyse 3D anatomy of the fused hip
      based on pre-operative computed tomography (CT) scans, functional outcomes based
      on the Harris Hip Score (HHS) and the Hip Disability and Osteoarthritis Outcome
      Score (HOOS), modifications of hip anatomy based on post-operative standardised
      radiography, and determine complication rate and long-term survival based on
      Kaplan-Meier analysis. METHODS: We retrospectively studied 23 hips that underwent
      conversion of a fused hip to THA using a 3D CT scan-based custom titanium (Ti
      alloy hypoxyapetite (HA)-coated stem. The mean follow-up was 15 (9-22) years.
      Femur anteversion ranged from -29 degrees  to 80 degrees . RESULTS: HHS improved
      from 59 to 89 points and average range of motion (ROM) was 88 degrees  for
      flexion. Back pain decreased in 62%, and knee pain decreased in 42%. The mean
      post-operative leg-length discrepancy was 7.8 mm. No intra-operative
      complications occurred. One aseptic stem loosening for mechanical failure was
      observed. The Kaplan-Meier survivorship considering revision for any reasons as
      the end point was 95.6% [95% confidence interval (CI) 92.4-98.8] at 15 years.
      CONCLUSION: Custom cementless stems may be an interesting solution to address the
      particular anatomical features of hip fusion at the time of THA, with an
      excellent survival rate at 15 years.

PMID- 29352334
TI  - Long-Term Follow-Up of Retromuscular Incisional Hernia Repairs: Recurrence and
      Quality of Life: Reply.

PMID- 29352335
TI  - Important Research Elements in Aiding Training: Reply.

PMID- 29352336
TI  - Who was Dr. William C. Baum?
AB  - The first discovery of primary hyperaldosteronism secondary to an aldosterone
      secreting adrenal adenoma has been credited solely to Dr. Jerome Conn, an
      endocrinologist at the University of Michigan and for whom, Conn syndrome was
      named. Dr. William Baum, a urologist at the University of Michigan, however, was
      instrumental in the appropriate operation and historical aldosteronoma resection.
      Despite Dr. Baum's important role in this discovery, he was never included as an
      author in any of the subsequent papers describing Conn syndrome and, few today
      would recognize his name. So, who was Dr. Baum and what happened? This historical
      article aims to revisit the history surrounding the discovery of aldosteronoma as
      a cause of Conn's syndrome and to catalog the life and involvement of Dr. William
      C. Baum in that discovery.

PMID- 29352337
TI  - Impact of Hepatitis B Carrier Status on the Outcomes of Surgical Treatment of
      Colorectal Liver Metastases.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a lower
      incidence of colorectal liver metastases. We explored the impact of HBV carrier
      status on outcomes of surgical treatment of colorectal liver metastases. METHODS:
      A retrospective analysis was conducted for consecutive patients undergoing liver
      resection for colorectal liver metastases from 2000 to 2016. HBV carriers were
      matched with controls by propensity scoring. RESULTS: 304 patients with known HBV
      carrier status who underwent resection of colorectal liver metastases were
      studied. From the 21 (6.9%) hepatitis B carriers, a more prolonged prothrombin
      time (12.1 vs. 11.3 s, OR 1.42, p = 0.027) was observed, and fewer major
      resections were performed (19.0 vs. 47.3%, OR 0.262, p = 0.018). After 1:5
      propensity score matching, they were compared with 105 controls with similar
      liver function, tumour status and receiving similar treatments. Patients with
      chronic hepatitis B enjoyed better median disease-free survival (15.8 vs. 9.20
      month, p = 0.032). Overall survivals (50.0 vs. 43.6 month, p = 0.15) were
      similar. Operating time (227 vs. 240 min, OR 1.00, p = 0.33), blood loss (0.50
      vs. 0.37 L, OR 1.15, p = 0.62), hospital stay (6 vs. 6 day, OR 1.02, p = 0.48),
      operative morbidity (9.5 vs. 16.2%, OR 0.545, p = 0.44) and mortality (0 vs.
      1.0%, OR 1.62, p = 0.77) were comparable. The use of antiviral agents did not
      affect survival of HBV carriers. CONCLUSIONS: Chronic HBV infection confers
      oncological benefit to surgical treatment of colorectal liver metastases. Given
      satisfactory liver reserve, HBV carrier status did not affect operative morbidity
      or mortality.

PMID- 29352338
TI  - Predictive Factors for Lymph Node Metastasis in Submucosal Invasive Colorectal
      Carcinoma: A New Proposal of Depth of Invasion for Radical Surgery.
AB  - BACKGROUND: Patients with lymph node metastasis (LNM) in submucosal invasive
      colorectal carcinoma (SM cancer) require additional surgical treatment after
      endoscopic dissection. However, because additional radical resection after
      endoscopic local resection may be unnecessary for cases without LNM, more
      specific criteria are required in order to diminish the incidence of further
      radical resection after endoscopic dissection. METHODS: A total of 492 patients
      with biopsy-proven SM cancer who underwent curative surgery between January 2008
      and December 2012 were collected and were divided into LNM group and no LNM
      group. The cutoff value for the depth of submucosal invasion was analyzed by a
      receiver operating characteristic (ROC) curve. In this retrospective study, the
      association between LNM and clinicopathologic factors was analyzed by logistic
      regression analysis. RESULTS: The depth of submucosal invasion of 1900 MUm was
      determined as the cutoff value by ROC curve. Significant, independent predictive
      factors for LNM included the depth of submucosal invasion >1900 MUm (odds ratio
      [OR] 7.5; 95% confidence interval [CI] 3.1-18.3; p < 0.001), venous invasion (OR
      2.4; 95% CI 1.1-5.5; p = 0.03), and poorly differentiated/mucinous adenocarcinoma
      (OR 6.3; 95% CI 1.3-30.8; p = 0.02). CONCLUSIONS: Our study demonstrates that the
      depth of submucosal invasion (>1900 MUm), vascular invasion and poorly
      differentiated/mucinous carcinoma were predictive factors of LNM in patients with
      SM cancer. These predictors may help to reduce the incidence of unnecessary
      surgery after endoscopic resection.

PMID- 29352340
TI  - Angiotensin-(1-7)-induced Mas receptor activation attenuates atherosclerosis
      through a nitric oxide-dependent mechanism in apolipoproteinE-KO mice.
AB  - Angiotensin (Ang)-(1-7) ameliorates vascular injury by increasing nitric oxide
      (NO) bioavailability. Evidence that Ang-(1-7) attenuates the development of
      atherosclerosis through a NO-dependent mechanism is still missing. Moreover, it
      has been postulated that Ang-(1-7) may mediate its effects by other mechanisms
      than Mas receptor activation. To investigate Ang-(1-7)-dependent Mas receptor
      function, we treated apoE-KO and apoE/Mas-KO mice chronically with Ang-(1-7) (82
      MUg/kg per hour) or saline for 6 weeks. Flow-mediated dilation (FMD), a measure
      for NO-dependent vasodilation and the most accepted prognostic marker for the
      development of atherosclerosis, was measured in vivo. Chronic Ang-(1-7) treatment
      improved FMD and attenuated the development of atherosclerosis in apolipoproteinE
      (apoE)-KO but not in apoE/Mas-KO mice. These effects were accompanied by
      increased aortic nitrite and cGMP levels. To test whether Ang-(1-7) modulates
      atherosclerosis through a NO-dependent mechanism, apoE-KO mice were treated with
      the NO synthase inhibitor L-NAME (20 mg/kg/day) in the presence or absence of Ang
      (1-7). L-NAME treatment reduced aortic nitrite content and increased blood
      pressure and exaggerated atherosclerosis compared to untreated apoE-KO mice. In L
      NAME-treated apoE-KO mice, chronic Ang-(1-7) treatment did not increase aortic
      nitrite content and consequently showed no effect on blood pressure and the
      development of atherosclerosis. The present study proves that Ang-(1-7) mediates
      its protective vascular effects through Mas receptor activation. Moreover, Ang-(1
      7)-mediated NO generation is essential for improving vascular function and
      prevents atherosclerosis in apoE-KO mice.

PMID- 29352341
TI  - [Technology for vulnerable older adults and their relatives : Possibilities and
      limits].

PMID- 29352339
TI  - Effect of Time to Operation on Value of Care in Acute Care Surgery.
AB  - BACKGROUND: As reimbursement models evolve, there is increasing emphasis on
      maximizing value-based care for inpatient conditions. We hypothesized that longer
      intervals between admission and surgery would be associated with worse outcomes
      and increased costs for acute care surgery patients, and that these associations
      would be strongest among patients with high-risk conditions. METHODS: We
      performed a 5-year retrospective analysis of three risk cohorts: appendectomy
      (low-risk for morbidity and mortality, n = 618), urgent hernia repair
      (intermediate-risk, n = 80), and laparotomy for intra-abdominal sepsis with
      temporary abdominal closure (sTAC; high-risk, n = 102). Associations between the
      interval from admission to surgery and outcomes including infectious
      complications, mortality, length of stay, and hospital charges were assessed by
      regression modeling. RESULTS: Median intervals between admission and surgery for
      appendectomy, hernia repair, and sTAC were 9.3, 13.5, and 8.1 h, respectively,
      and did not significantly impact infectious complications or mortality. For
      appendectomy, each 1 h increase from admission to surgery was associated with
      increased hospital LOS by 1.1 h (p = 0.002) and increased intensive care unit
      (ICU) LOS by 0.3 h (p = 0.011). For hernia repair, each 1 h increase from
      admission to surgery was associated with increased antibiotic duration by 1.6 h
      (p = 0.007), increased hospital LOS by 3.3 h (p = 0.002), increased ICU LOS by
      1.5 h (p = 0.001), and increased hospital charges by $1918 (p < 0.001). For sTAC,
      each 1 h increase from admission to surgery was associated with increased
      antibiotic duration by 5.0 h (p = 0.006), increased hospital LOS by 3.9 h (p =
      0.046), increased ICU LOS by 3.5 h (p = 0.040), and increased hospital charges by
      $3919 (p = 0.002). CONCLUSIONS: Longer intervals from admission to surgery were
      associated with prolonged antibiotic administration, longer hospital and ICU
      length of stay, and increased hospital charges, with strongest effects among high
      risk patients. To improve value of care for acute care surgery patients,
      operations should proceed as soon as resuscitation is complete.

PMID- 29352342
TI  - ?

PMID- 29352346
TI  - The Evolution of Breast Reduction Publications: A Bibliometric Analysis.
AB  - OBJECTIVE: This study aims to make a bibliometric analysis of the studies on
      breast reduction (BR) between the years 1980 and 2016 and identify important
      studies through trend topics as well as active authors, countries, universities,
      scientific journals, and citation and co-citation analyses about BR. BACKGROUND:
      Although BR looks like one of the cosmetic surgeries performed in order to
      restore the woman's appearance, in fact it is a reconstructive surgery that
      eliminates back pain, stance disorder, headache, shoulder pain, back and cervical
      disk hernia, difficulty in breathing, hollowness caused by bra straps, hygiene
      problems under breasts (e.g., rash or fungal infections), and limitations in some
      daily activities. However, the related literature has little information about
      the publications on this issue. METHODS: Bibliometric analysis was performed by
      downloading all the documents published between 1980 and 2016 from Thomson
      Reuters Web of Science (WoS; Thomson Reuters, New York, NY, USA), using the
      keywords including "breast reduction", "gigantomastia", "reduction mammaplasty",
      and "reduction mammoplasty". RESULTS: There was a total of 1427 publications in
      the WoS database. Of these publications, 869 (60.90%) were research articles. The
      top three research areas of these publications were surgery with 1178 (82.55%)
      publications, oncology with 78 (5.47%) publications, and obstetrics gynecology
      with 67 (4.70%) publications. The top three countries that contributed to the
      literature most were the USA (515), England (147), and Turkey (83), respectively;
      the top university that contributed most was Harvard University, and the top two
      authors who contributed most were Drew PJ and Iwuagwu OC (13; 0.91%). The top
      cited publication was "A Simplified Vertical Reduction Mammaplasty: Shortening
      the Learning Curve" written by Hall-Findlay, EJ in 1999. The journals with top
      numbers of publications were Plastic and Reconstructive Surgery (483; 33.85%),
      Annals of Plastic Surgery (164; 11.50%) and Aesthetic Plastic Surgery (147;
      10.30%) respectively. CONCLUSION: Despite the fact that the BR literature is
      contributed by developed countries, developing countries, particularly Turkey and
      Brazil, also had significant contributions to the literature. LEVEL OF EVIDENCE
      V: This journal requires that authors assign a level of evidence to each article.
      For a full description of these evidence-based medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 29352347
TI  - Autologous cell-based therapy for treatment of large bone defects: from bench to
      bedside.
AB  - OBJECTIVES: Reconstruction of long segmental bone defects is demanding for
      patients and surgeons, and associated with long-term treatment periods and
      substantial complication rates in addition to high costs. While defects up to 4-5
      cm length might be filled up with autologous bone graft, heterologous bone from
      cadavers, or artificial bone graft substitutes, current options to reconstruct
      bone defects greater than 5 cm consist of either vascularized free bone
      transfers, the Masquelet technique or the Ilizarov distraction osteogenesis.
      Alternatively, autologous cell transplantation is an encouraging treatment option
      for large bone defects as it eliminates problems such as limited autologous bone
      availability, allogenic bone immunogenicity, and donor-site morbidity, and might
      be used for stabilizing loose alloplastic implants. METHODS: The authors show
      different cell therapies without expansion in culture, with ex vivo expansion and
      cell therapy in local bone defects, bone healing and osteonecrosis. Different
      kinds of cells and scaffolds investigated in our group as well as in vivo
      transfer studies and BMC used in clinical phase I and IIa clinical trials of our
      group are shown. RESULTS: Our research history demonstrated the great potential
      of various stem cell species to support bone defect healing. It was clearly shown
      that the combination of different cell types is superior to approaches using
      single cell types. We further demonstrate that it is feasible to translate
      preclinically developed protocols from in vitro to in vivo experiments and follow
      positive convincing results into a clinical setting to use autologous stem cells
      to support bone healing.

PMID- 29352348
TI  - Metarhizium anisopliae s.l. modulation of lipid metabolism during tick infection
      is independent of AMPK and ERK pathways.
AB  - Despite the importance of fat body in metabolism of arthropods, studies in ticks
      are scarce. This study evaluated the lipid composition and activation of
      extracellular signal-regulated protein kinase (ERK) and AMP-activated protein
      kinase (AMPK) enzymes in Rhipicephalus microplus fat body after infection with
      different isolates of the fungus Metarhizium anisopliae sensu lato (Metschnikoff,
      1879) Sorokin, 1883. The isolates CG 32, GC 112, GC 148, GC 347, and GC 629 were
      inoculated as viable or non-viable conidia in the ticks. The engorged females
      were dissected, and their fat bodies were collected 24 and 48 h after infection.
      The lipid composition was assessed by thin layer chromatography, and enzyme
      activation was detected by Western blotting with antibodies against p-AMPK and p
      ERK. The study showed increased levels of triacylglycerol 24 and 48 h and fatty
      acid after 48 h after inoculation with different isolates of viable fungi in the
      tick's hemocoel. Detection of the active form of ERK was demonstrated only after
      inoculation with non-viable conidia of all isolates tested. The active form of
      AMPK, only isolate CG 112 was able to activate with viable or non-viable conidia,
      whereas isolates CG 32 and CG 629 were able to activate with non-viable conidia.
      This study provides the first report about changes in important metabolic
      pathways in ticks infected with entomopathogenic fungi and suggests that the
      lipid content is modulated by non-usual pathways. However, further studies may be
      necessary for a better elucidation of this interaction.

PMID- 29352349
TI  - Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm
      infants and use in determination of haemodynamic significance of patent ductus
      arteriosus.
AB  - : This study aimed to investigate factors affecting N-terminal pro-B-type
      natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to
      predict haemodynamically significant patent ductus arteriosus (HsPDA).
      Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and
      heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected
      age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational
      age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and
      haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had
      higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p <
      0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and
      day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen
      day 3 NTproBNP value of >= 287 pmol/L for the prediction of day 3 HsPDA correctly
      classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only
      modest ability to predict severe BPD. Chronological but not gestational age
      affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence
      NTproBNP but creatinine level was positively correlated. CONCLUSION: Day 3
      NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in
      future trial design. What is Known: * NTproBNP is a cardiac hormone used to
      diagnose and monitor cardiac dysfunction in adults and has been shown to be
      higher in premature infants with haemodynamically significant ductus arteriosus
      (HsPDA). What is new: * NTproBNP is highly predictive of ultrasound-defined HsPDA
      and may be a useful tool for further triage * Early NTproBNP higher in infants
      who develop severe BPD and with renal impairment but not affected by gestational
      age, recent exposure to hypoxia or haemoglobin levels while late levels
      unexpectedly higher in those without BPD or HsPDA.

PMID- 29352350
TI  - Groundwater quality assessment in semi-arid regions using integrated approaches:
      the case of Grombalia aquifer (NE Tunisia).
AB  - As many arid and semi-arid regions in the Mediterranean Basin, the Grombalia
      coastal aquifer (NE Tunisia) is affected by severe groundwater exploitation and
      contamination. Therefore, quality assessments are becoming increasingly important
      as the long-term protection of water resources is at stake. Multidisciplinary
      investigations, like the one presented in this paper, are particularly effective
      in identifying the different origins of mineralization within an aquifer and
      investigating the impact of anthropogenic activities on groundwater quality. An
      integrated assessment, focused on the combined use of geostatistical, geochemical
      and isotopic (delta18O, delta2H and 3H) tools, was performed in the Grombalia
      aquifer between February and March 2014. The overall goal was to study the main
      processes controlling aquifer salinization, with special focus to nitrate
      contamination. Results indicate a persisting deterioration of water quality over
      the whole basin except the south-eastern zone juxtaposing the recharge area of
      the aquifer. Nitrate contents exceed the drinking water standard (50 mg/l) in 70%
      of groundwater samples, mainly due to the excessive use of fertilizers and urban
      activities. Stable isotope measurements showed the contribution of modern
      rainwater to aquifer recharge and proved the presence of evaporation contributing
      to the salinity increase. Tritium values of groundwater samples suggested two
      hypotheses: the existence of mixture between old and recent water or/and the
      existence of two recharge periods of the aquifer, pre- and post-nuclear weapons
      test. Principal component analysis confirmed the geochemical interpretation,
      highlighting that water-rock interaction evaporation effect and intensive
      anthropogenic activities constitute the main processes controlling the regional
      groundwater mineralization.

PMID- 29352351
TI  - Levodopa-induced dyskinesia in Parkinson's disease: still no proof? A meta
      analysis.
AB  - We investigated whether there is a linear relationship between levodopa (LD) dose
      and treatment duration, and the development of levodopa-induced dyskinesia (LID)
      among patients with early untreated Parkinson's disease (PD). We performed a meta
      analysis of randomized-controlled trials (RCTs) comparing LD monotherapy to any
      other antiparkinsonian treatment in early PD patients. Meta-regressions were
      conducted including as covariates the effects of LD dose, treatment duration, and
      age. We further proceeded in subgroup analyses based on the type of medications
      in the non-LD monotherapy (control) group and on whether patients in the control
      group received additional levodopa or not. Thirteen eligible RCTs were included,
      which revealed a significantly higher risk for dyskinesia in patients initially
      treated with LD monotherapy compared to any other treatment (OR = 2.82). None of
      the subsequent meta-regressions revealed any significant relationship with dose,
      treatment duration or age. Patients treated on LD monotherapy or MAOIota plus LD
      were at a greater risk to develop LID than patients who received DA only or DA
      plus supplemental LD. The increased heterogeneity compromised the robustness of
      the results. The alleged correlation between LID and LD dose and treatment
      duration cannot be verified based on the data available so far. Well-designed,
      large-scale, long-term, RCTs on drug-naive PD patients could allow the better
      comprehension of the pattern of the association between LID and LD treatment
      parameters.

PMID- 29352352
TI  - Morphology, Structure, and Optical Properties of Semiconductor Films with GeSiSn
      Nanoislands and Strained Layers.
AB  - The dependences of the two-dimensional to three-dimensional growth (2D-3D)
      critical transition thickness on the composition for GeSiSn films with a fixed Ge
      content and Sn content from 0 to 16% at the growth temperature of 150  degrees S
      have been obtained. The phase diagrams of the superstructure change during the
      epitaxial growth of Sn on Si and on Ge(100) have been built. Using the phase
      diagram data, it becomes possible to identify the Sn cover on the Si surface and
      to control the Sn segregation on the superstructure observed on the reflection
      high-energy electron diffraction (RHEED) pattern. The multilayer structures with
      the GeSiSn pseudomorphic layers and island array of a density up to 1.8 * 1012 cm
      2 have been grown with the considering of the Sn segregation suppression by the
      decrease of GeSiSn and Si growth temperature. The double-domain (10 * 1)
      superstructure related to the presence of Sn on the surface was first observed in
      the multilayer periodic structures during Si growth on the GeSiSn layer. The
      periodical GeSiSn/Si structures demonstrated the photoluminescence in the range
      of 0.6-0.85 eV corresponding to the wavelength range of 1.45-2 MUm. The
      calculation of the band diagram for the structure with the pseudomorphic
      Ge0.315Si0.65Sn0.035 layers allows assuming that photoluminescence peaks
      correspond to the interband transitions between the X valley in Si or the Delta4
      valley in GeSiSn and the subband of heavy holes in the GeSiSn layer.

PMID- 29352353
TI  - Regarding loads after spinal fusion, every level should be seen separately: a
      musculoskeletal analysis.
AB  - INTRODUCTION: The number of spinal fusion surgeries is steadily increasing and
      biomechanical consequences are still in debate. The aim of this study is to
      provide biomechanical insights into the sagittal balance of the spine and to
      compare spinal load before and after spinal fusion. METHOD: The joint reaction
      forces of 52 patients were analyzed in proximo-distal and antero-posterior
      direction from the levels T12-L1 to L5-S1 using musculoskeletal simulations.
      RESULTS: In 104 simulations, pre-surgical forces were equal to post-surgical. The
      levels L4-L5 and T12-L1, however, showed increased spinal forces compression
      forces with higher sagittal displacement. Improved restauration of sagittal
      balance was accompanied by lower spinal load. AP shear stress, interestingly
      decreased with sagittal imbalance. CONCLUSION: Imbalanced spines have a risk of
      increased compression forces at Th12-L1. L4-L5 always has increased spinal loads.
      These slides can be retrieved under Electronic Supplementary Material.

PMID- 29352354
TI  - Answer to the Letter to the Editor of P. Kumar et al. concerning "Clinical and
      radiological factors related to the presence of motor deficit in lumbar disc
      prolapse: a prospective analysis of 70 consecutive cases with neurological
      deficit" by V. Krishnan et al. [Eur Spine J (2017) 26:2642-2649].

PMID- 29352356
TI  - Assessment of noise level and noise propagation generated by light-lift
      helicopters in mountain natural environments.
AB  - The use of helicopter rises discussion about environmental noise propagation
      especially when it operates in proximity of environmentally sensitive areas
      (ESAs) for an extended period because of its potential implications in wildlife
      behaviours. In order to support decisions on helicopter logging operation
      management in proximity of ESAs, this study focused on (i) analysing the noise
      spectrum of a light-lift helicopter during logging operations and on (ii)
      assessing the noise propagation in the surrounding environments. This study
      investigated a helicopter logging operation for wood fuel extraction in the
      eastern part of the Italian Alps. The potential disturbance area covered for the
      entire helicopter logging operation was evaluated by a specific GIS application
      according to hearing sensitivity of the most sensitive wildlife species in the
      study area (different strigiform species). The noise level at the ground appeared
      to be affected by the location regardless both the use of equivalent continuous
      sound pressures level dB(A) (LAeq) and the single-event level (SEL) noise
      metrics. The lowest values were recorded when the helicopter was flown over the
      sound meter level located under the forest canopy, while the highest was recorded
      when the helicopter was unhooking the loads at the landing. The GIS application
      highlighted the consistent of the exceeded noise area (weighted to strigiform
      hearing range and sensitivity) for the lower frequency bands (0.016-0.250 kHz). A
      more restricted exceeded noise area concerned instead the most sensitive
      frequency bands" for the strigiform (1-2 kHz). Graphical abstract ?.

PMID- 29352355
TI  - Physiological responses to salt stress of salt-adapted and directly salt (NaCl
      and NaCl+Na2SO4 mixture)-stressed cyanobacterium Anabaena fertilissima.
AB  - Soil salinity in nature is generally mixed type; however, most of the studies on
      salt toxicity are performed with NaCl and little is known about sulfur type of
      salinity (Na2SO4). Present study discerns the physiologic mechanisms responsible
      for salt tolerance in salt-adapted Anabaena fertilissima, and responses of
      directly stressed parent cells to NaCl and NaCl+Na2SO4 mixture. NaCl at 500 mM
      was lethal to the cyanobacterium, whereas salt-adapted cells grew luxuriantly.
      Salinity impaired gross photosynthesis, electron transport activities, and
      respiration in parent cells, but not in the salt-adapted cells, except a marginal
      increase in PSI activity. Despite higher Na+ concentration in the salt mixture,
      equimolar NaCl appeared more inhibitive to growth. Sucrose and trehalose content
      and antioxidant activities were maximal in 250 mM NaCl-treated cells, followed by
      salt mixture and was almost identical in salt-adapted (exposed to 500 mm NaCl)
      and control cells, except a marginal increase in ascorbate peroxidase activity
      and an additional fourth superoxide dismutase isoform. Catalase isoform of 63 kDa
      was induced only in salt-stressed cells. Salinity increased the uptake of
      intracellular Na+ and Ca2+ and leakage of K+ in parent cells, while cation level
      in salt-adapted cells was comparable to control. Though there was differential
      increase in intracellular Ca2+ under different salt treatments, ratio of Ca2+/Na+
      remained the same. It is inferred that stepwise increment in the salt
      concentration enabled the cyanobacterium to undergo priming effect and acquire
      robust and efficient defense system involving the least energy.

PMID- 29352357
TI  - An Investigation of the Post-laryngectomy Swallow Using Videofluoroscopy and
      Fiberoptic Endoscopic Evaluation of Swallowing (FEES).
AB  - This study investigates the post-laryngectomy swallow. Presence and degree of
      residue on the post-laryngectomy swallow as observed on videofluoroscopy and FEES
      is described. In addition, videofluoroscopy and FEES are assessed for reliability
      and inter-instrument agreement. 30 laryngectomy subjects underwent dysphagia
      evaluation using simultaneous videofluoroscopy and FEES. These were reviewed post
      examination by three expert raters using a rating scale designed for this
      purpose. Raters were blinded to subject details, type of laryngectomy surgery,
      pairing of FEES and videofluoroscopy examinations and the scores of other raters.
      There was a finding of residue in 78% of videofluoroscopy ratings, and 83% of
      FEES ratings. Comparison of the tools indicated poor inter-rater reliability and
      poor inter-instrument agreement. Dysphagia is an issue post laryngectomy as
      measured by patient self-report and by instrumental evaluation. However,
      alternative dysphagia rating tools and dysphagia evaluation tools are required to
      enable accurate identification and intervention for underlying swallow physiology
      post laryngectomy.

PMID- 29352358
TI  - Daily Fantasy Sports Players: Gambling, Addiction, and Mental Health Problems.
AB  - Studies point to a relationship between fantasy sports/daily fantasy sports (DFS)
      play and gambling behavior. However, little is known about the nature of those
      relationships, particularly regarding the development of gambling problems. This
      study investigates the nature, frequency, and preferences of gambling behavior as
      well as problem gambling severity and comorbid conditions among DFS players. Data
      were collected from an epidemiologic survey of 3634 New Jersey residents on
      gambling and leisure activities. Participants were contacted by phone (land-line
      and cell) and online to obtain a representative, cross-sectional sample of non
      institutionalized adults, aged 18 years or older. Excluding non-gamblers, the
      remaining 2146 participants, included in these analyses, indicated they had
      either played DFS (n = 299) or had gambled but not played DFS (1847) in the past
      year. Univariate comparisons and multiple logistic regression analyses were
      performed to identify the most significant characteristics and predictors of DFS
      players. Overall, a higher number of gambling activities, high frequency
      gambling, male gender, and reports of suicidal thoughts in the past year were
      most predictive of DFS players. Being Hispanic (vs. Caucasian) and/or single (vs.
      married or living with a partner) also doubled the odds of DFS play. Findings
      suggest that DFS players are characterized by high gambling frequency and problem
      severity and comorbid problems, notably suicidal ideation. Future research should
      examine the motivations and possible etiological sub-types of DFS players and the
      nature and course of DFS play, particularly in relation to gambling behavior and
      the development of gambling and other problems.

PMID- 29352359
TI  - Unilateral Lichtenstein tension-free mesh hernia repair and testicular perfusion:
      a prospective control study.
AB  - PURPOSE: Compare testicular perfusion between the herniated and the healthy side
      pre- and post-surgery. MATERIALS AND METHODS: Our study was done on patients with
      unilateral inguinal hernia. A Doppler ultrasound study was performed in the
      healthy and herniated side before surgery and 3 months after it. RESULTS: 31
      patients were included, 74.2% on the right and 25.8% on the left side. When
      comparing the pre-surgical values of testicular resistance index from the healthy
      side with those on the herniated side, there was a significant difference at the
      spermatic cord levels (0.73 +/- 0.11 and 0.81 +/- 0.13, p = 0.018) and the extra
      testicular level (0.66 +/- 0.92 and 0.74 +/- 0.10, p = 0.032), but a significant
      difference was not present at the intra-testicular level (0.62 +/- 0.07 and 0.65
      +/- 0.08). Three months after the surgery, there were no statistically
      significant differences at any of the levels studied. CONCLUSION: There are no
      intra-testicular perfusion differences caused by the presence of hernia, nor
      during post-surgery.

PMID- 29352360
TI  - Quality of life in obstructive sleep apnea is related to female gender and
      comorbid insomnia.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is a common sleep disorder affecting
      health-related quality of life (QoL), and OSA severity is not a reliable
      indicator for QoL. The aim of this study was (1) to evaluate the impact of gender
      on QoL and (2) to identify the predictors of QoL in OSA patients. METHODS: World
      Health Organization Quality of Life Scale short form (WHOQOL-Bref) was used for
      evaluating QoL in OSA patients undergoing polysomnography in sleep laboratory of
      a university hospital. RESULTS: Out of 197 patients (age 50.4 +/- 12.1 years, AHI
      38.5 +/- 28.4/h), 139 (70.6%) were men and 79.2% had moderate-to-severe OSA.
      Female gender, increased BMI, higher Epworth sleepiness score (ESS), and lower
      oxygen saturations were associated significantly with poor QoL in terms of all
      domains (physical, psychological, social relationship, and environmental) of
      WHOQOL-Bref questionnaire. The indicators of OSA severity (AHI and ODI)
      correlated negatively only with the physical domain. The subjects with comorbid
      insomnia and OSA had lower physical and social scores than subjects with no
      insomnia, and women with insomnia had significantly worse QoL scores in all
      domains than the others. In the multivariate linear regression analysis, female
      gender, comorbid insomnia, increased sleepiness, and higher BMI were
      significantly associated with poor QoL. CONCLUSIONS: Female gender, comorbid
      insomnia, and daytime sleepiness were the outstanding factors affecting health
      related QoL negatively in OSA. Besides, the impact of OSA on QoL may be explained
      by the presence of daytime sleepiness rather than OSA severity.

PMID- 29352361
TI  - The modified Ravitch approach for the management of severe anterior flail chest
      with bilateral sternochondral dislocations: a case report.
AB  - The management of flail chest continues to evolve as scientific evidence and
      surgical experience accumulates. Flail chest injuries that span the sternum
      present a rare and complicated injury pattern that can be challenging to manage
      both medically and surgically. Our patient is a 69-year-old involved in a high
      speed motor vehicle crash with respiratory failure secondary to an anterior flail
      chest. Tomographic examination confirmed a sternal fracture with bilateral
      sternochondral dislocations and multiple rib fractures. The rib fractures created
      a lateral flail segment which extended towards the right side. An open Pectus
      exposure with a right anterolateral extension (modified Ravitch approach) and
      osteosynthesis plates accomplished stabilization of the chest wall, and
      contributed to weaning from mechanical ventilation.

PMID- 29352362
TI  - A Preliminary Examination of the Link Between Maternal Experiential Avoidance and
      Parental Accommodation in Anxious and Non-anxious Children.
AB  - Studies point to parental experiential avoidance (EA) as a potential correlate of
      maladaptive parenting behaviors associated with child anxiety. However, research
      has not examined the relationship between EA and parental accommodation of child
      anxiety, nor the extent to which parental negative beliefs about child anxiety
      help explain such a relationship. In a sample of mothers (N = 45) of anxious and
      non-anxious children, the present study investigated the potential link between
      maternal EA and accommodation of child anxiety and whether this link may be
      indirectly accounted for via maternal negative beliefs about child anxiety. EA
      was significantly and positively associated with accommodation of child anxiety,
      but when negative beliefs about child anxiety were incorporated into the model
      this direct effect was no longer significant. Findings highlight the contribution
      of parental emotions and cognitions to behaviors that may exacerbate child
      anxiety, and may inform treatment and prevention efforts with families of anxious
      youth.

PMID- 29352363
TI  - [Preclinical emergency medicine-thinking outside the box is worth it!]

PMID- 29352364
TI  - [Accidental central venous administation of 0.1 % chlorhexidine mouthwash].
AB  - Medication errors are frequent and a serious safety concern. Chlorhexidine (CHX)
      is used daily in healthcare as a disinfectant. Its accidental intravascular
      injection is scarcely described. Serious complications, such as acute respiratory
      distress syndrome (ARDS) could be a consequence. We describe a case of central
      venous administration of 0.1% CHX mouthwash, its potential complications and
      possibilities of treatment. In contrast to another case report our patient had no
      detectable adverse side effects. The immediate hemofiltration and cleansing of
      the i. v. line may have contributed to this favorable outcome.

PMID- 29352365
TI  - [Anesthesia problem cards-indispensable yet problematic : Nationwide survey on
      experiences from clinical practice].
AB  - BACKGROUND: Anesthetic procedures may lead to severe and potentially life
      threatening complications (e. g. difficult airway, allergic reactions, malignant
      hyperthermia). Most complications can be avoided in future anesthetic procedures
      with adequate preparation (e. g. awake intubation, trigger-free anesthesia). In
      Germany, anesthesia problem cards were introduced two decades ago to identify
      patients at risk and to increase patient safety by creating a standardized
      documentation system for anesthesia-related complications. The purpose of our
      study was to evaluate the utility and problems of anesthesia problem cards in
      clinical practice. MATERIAL AND METHODS: All registered members of the German
      Society of Anesthesiology and Intensive Care Medicine (DGAI) and the Professional
      Association of German Anesthesiologists (BDA) (n = 19,042) were invited to
      participate in an online survey on patient safety. A subsection of the survey
      focused specifically on anesthesia problem cards and their utility in clinical
      practice (e. g. field of application, issuing procedures, benefits and problems).
      RESULTS: The survey subsection on anesthesia problem cards was completed by 1783
      participants. Most agreed that anesthesia problem cards are a useful tool to
      increase patient safety (n = 1502; 84.2%) and that they are routinely issued
      after the occurrence of anesthesia-related complications (n = 1664, 93.4%). One
      of the major problems noted was that patients frequently forget to bring their
      anesthesia problem cards when presenting for the preanesthetic assessment. This
      was observed by 1457 participants (81.7%). Furthermore, the information provided
      on anesthesia problem cards may be inadequately phrased (n = 874; 49.0%) or
      illegible (n = 833; 46.7%). In addition, the space for individual comments or
      problem solutions is insufficient (n = 811; 45.5%). Replacements for lost
      anesthesia problem cards with identical informational content can be issued in
      only 41.9% (n = 747) of the participants' departments. CONCLUSION: Anesthesia
      problem cards are considered a useful tool to increase patient safety and are
      frequently issued in clinical practice; however, in the document's current form
      its full potential for risk minimization cannot be exploited. Structural changes
      are required to increase documentation quality and reproducibility. Concerning
      its informational content, the spectrum of included complications and their
      individual solutions need to be expanded to meet the requirements of modern
      anesthetic practice.

PMID- 29352366
TI  - A new class of CEST experiment based on selecting different magnetization
      components at the start and end of the CEST relaxation element: an application to
      1H CEST.
AB  - Chemical exchange saturation transfer (CEST) experiments are becoming
      increasingly popular for investigating biomolecular exchange dynamics with rates
      on the order of approximately 50-500 s-1 and a rich toolkit of different methods
      has emerged over the past few years. Typically, experiments are based on the
      evolution of longitudinal magnetization, or in some cases two-spin order, during
      a fixed CEST relaxation delay, with the same class of magnetization prepared at
      the start and selected at end of the CEST period. Here we present a pair of TROSY
      based pulse schemes for recording amide and methyl 1H CEST profiles where
      longitudinal magnetization at the start evolves to produce two-spin order that is
      then selected at the completion of the CEST element. This selection process
      subtracts out contributions from 1H-1H cross-relaxation on the fly that would
      otherwise complicate analysis of the data. It also obviates the need to record
      spin-state selective CEST profiles as an alternative to eliminating NOE effects,
      leading to significant improvements in sensitivity. The utility of the approach
      is demonstrated on a sample of a cavity mutant of T4 lysozyme that undergoes
      chemical exchange between conformations where the cavity is free and occupied.

PMID- 29352367
TI  - Continuous manufacturing of co-crystals: challenges and prospects.
AB  - The last decade has witnessed extensive growth in the field of co-crystallization
      for mitigating the solubility and dissolution-related issues of poorly soluble
      drugs. This is largely because co-crystals can modify the physicochemical
      properties of drugs without any covalent modification in the drug molecules. The
      US Food and Drug Administration (FDA) now considers drug products that are
      designed to contain a new co-crystal, analogous to new polymorph of the active
      pharmaceutical ingredient (API). This positive change in regulatory perspective
      coupled with successful commercialization of valsartan-sacubitril co-crystal
      (Entresto, Novartis) has now brought co-crystals into focus, in both industries
      as well as academia. Co-crystal prediction, screening, and synthesis have been
      reported in literature; however, co-crystal production at a larger scale needs
      further investigations. With this aim, the article describes various continuous
      methods for co-crystal production, along with in-line monitoring during co
      crystal production, emphasizing on process analytical technology (PAT). In
      addition, the scale-up issues of continuous and batch co-crystallization and
      other suitable techniques for pharmaceutical scale up are detailed. Quality
      control aspects and regulatory viewpoint crucial for commercial success are
      elaborated in the future perspective.

PMID- 29352368
TI  - Endocrine therapy and related issues in hormone receptor-positive early breast
      cancer: a roundtable discussion by the breast cancer therapy expert group
      (BCTEG).
AB  - PURPOSE: Management of breast cancer is a rapidly evolving field, and, although
      evidence-based guidelines are available for clinicians to provide direction on
      critical issues in patient care, clinicians often left to address these issues in
      the context of community practice situations with their patients. These include
      the patient's comorbid conditions, actual versus perceived benefit of treatments,
      patient's compliance as well as financial/reimbursement issues, and long-term
      tolerability of therapy. METHODS: A meeting of global oncology experts was
      convened in January 2017 with the belief that there is a gap in clinical practice
      guidance on several fundamental issues in breast cancer care, particularly in the
      community setting, where oncologists may encounter multiple tumor types. The goal
      was to discuss some of the most important questions in this area and provide some
      guidance for practicing oncologists. RESULTS: Topics addressed included risk of
      contralateral breast cancer recurrence in patients with estrogen receptor
      positive early breast cancer who have undergone 5 years of adjuvant endocrine
      therapy, adverse events associated with endocrine therapy and their management,
      emergent data on adjuvant bisphosphonate therapy and its apparent benefit in
      reducing breast cancer recurrence, recent findings of extended adjuvant endocrine
      therapy trials, and the use of currently available genomic biomarker tests as a
      means of further informing treatment decisions. CONCLUSIONS: A summary of the
      discussion on these topics and several 'expert opinion statements' are provided
      herein in an effort to convey the collective insights of the panel as it relates
      to current standard practice.

PMID- 29352369
TI  - Analysis of the succession of structure of the bacteria community in soil from
      long-term continuous cotton cropping in Xinjiang using high-throughput
      sequencing.
AB  - The present study aimed to identify the structural succession of the bacteria
      community in soil during long-term continuous cotton cropping and its
      relationship with continuous cropping obstacles in Xinjiang, China. High
      throughput sequencing was used to analyze and compare the composition of the
      bacterial community in the soil at the cotton root zone after years of continuous
      cotton cropping and crop rotation over 30 years of cultivation. Cotton
      cultivation increased the structural diversity of the bacterial community, among
      which the populations of Actinobacteria, Acidobacteria, Firmicutes, Nitrospirae,
      and Chloroflexi changed considerably. A 0-year sample and samples after
      continuous short- and long-term cropping, along with some with crop rotation,
      were gathered into three individual clusters. The findings of the rotation sample
      were similar to those of the sample of continuous long-term cropping. Cropping is
      the main cause of changes in the structure of the bacteria community; however,
      the new structure formed under continued duress of both long-term cotton
      cultivation and the associated farming methods gradually stabilizes after 10
      years of repeated fluctuations. Crop rotation can lead to the rapid recovery of
      some species of soil bacteria.

PMID- 29352370
TI  - Integrating Behavioral Health Services into Primary Care: Spotlight on the
      Primary Care Behavioral Health (PCBH) Model of Service Delivery.

PMID- 29352372
TI  - Improving PET Quantification of Small Animal [68Ga]DOTA-Labeled PET/CT Studies by
      Using a CT-Based Positron Range Correction.
AB  - PURPOSE: Image quality of positron emission tomography (PET) tracers that emits
      high-energy positrons, such as Ga-68, Rb-82, or I-124, is significantly affected
      by positron range (PR) effects. PR effects are especially important in small
      animal PET studies, since they can limit spatial resolution and quantitative
      accuracy of the images. Since generators accessibility has made Ga-68 tracers
      wide available, the aim of this study is to show how the quantitative results of
      [68Ga]DOTA-labeled PET/X-ray computed tomography (CT) imaging of neuroendocrine
      tumors in mice can be improved using positron range correction (PRC). PROCEDURES:
      Eighteen scans in 12 mice were evaluated, with three different models of tumors:
      PC12, AR42J, and meningiomas. In addition, three different [68Ga]DOTA-labeled
      radiotracers were used to evaluate the PRC with different tracer distributions:
      [68Ga]DOTANOC, [68Ga]DOTATOC, and [68Ga]DOTATATE. Two PRC methods were evaluated:
      a tissue-dependent (TD-PRC) and a tissue-dependent spatially-variant correction
      (TDSV-PRC). Taking a region in the liver as reference, the tissue-to-liver ratio
      values for tumor tissue (TLRtumor), lung (TLRlung), and necrotic areas within the
      tumors (TLRnecrotic) and their respective relative variations (DeltaTLR) were
      evaluated. RESULTS: All TLR values in the PRC images were significantly different
      (p < 0.05) than the ones from non-PRC images. The relative differences of the
      tumor TLR values, respect to the case with no PRC, were DeltaTLRtumor 87 +/- 41 %
      (TD-PRC) and 85 +/- 46 % (TDSV-PRC). TLRlung decreased when applying PRC, being
      this effect more remarkable for the TDSV-PRC method, with relative differences
      respect to no PRC: DeltaTLRlung = - 45 +/- 24 (TD-PRC), - 55 +/- 18 (TDSV-PRC).
      TLRnecrotic values also decreased when using PRC, with more noticeable
      differences for TD-PRC: DeltaTLRnecrotic = - 52 +/- 6 (TD-PRC), - 48 +/- 8 (TDSV
      PRC). CONCLUSION: The PRC methods proposed provide a significant quantitative
      improvement in [68Ga]DOTA-labeled PET/CT imaging of mice with neuroendocrine
      tumors, hence demonstrating that these techniques could also ameliorate the
      deleterious effect of the positron range in clinical PET imaging.

PMID- 29352371
TI  - Innate and adaptive T cells in influenza disease.
AB  - Influenza is a major global health problem, causing infections of the respiratory
      tract, often leading to acute pneumonia, life-threatening complications and even
      deaths. Over the last seven decades, vaccination strategies have been utilized to
      protect people from complications of influenza, especially groups at high risk of
      severe disease. While current vaccination regimens elicit strain-specific
      antibody responses, they fail to generate cross-protection against seasonal,
      pandemic and avian viruses. Moreover, vaccines designed to generate influenza
      specific T-cell responses are yet to be optimized. During natural infection,
      viral replication is initially controlled by innate immunity before adaptive
      immune responses (T cells and antibody-producing B cells) achieve viral clearance
      and host recovery. Adaptive T and B cells maintain immunological memory and
      provide protection against subsequent infections with related influenza viruses.
      Recent studies also shed light on the role of innate T-cells (MAIT cells,
      gammadelta cells, and NKT cells) in controlling influenza and linking innate and
      adaptive immune mechanisms, thus making them attractive targets for vaccination
      strategies. We summarize the current knowledge on influenza-specific innate MAIT
      and gammadelta T cells as well as adaptive CD8+ and CD4+ T cells, and discuss how
      these responses can be harnessed by novel vaccine strategies to elicit cross
      protective immunity against different influenza strains and subtypes.

PMID- 29352374
TI  - Quantification of myocardial blood flow and myocardial flow reserve with SPECT
      imaging technique.

PMID- 29352373
TI  - Sleep Interventions Designed to Improve Athletic Performance and Recovery: A
      Systematic Review of Current Approaches.
AB  - BACKGROUND: Athletes experience various situations and conditions that can
      interfere with their sleep, which is crucial for optimal psychological and
      physiological recovery as well as subsequent performance. Conventional sleep
      screening and intervention approaches may not be efficacious for athletes given
      their lifestyle, the demands of training and travel associated with
      interstate/international competition. OBJECTIVES: The present systematic review
      aimed to summarize and evaluate sleep intervention studies targeting subsequent
      performance and recovery in competitive athletes. Based on the findings, a
      secondary aim was to outline a possible sleep intervention for athletes,
      including recommendations for content, mode of delivery and evaluation. METHODS:
      A systematic review was conducted based on the PRISMA guidelines in May 2016 with
      an update completed in September 2017. Ten studies met our inclusion criteria
      comprising a total of 218 participants in the age range of 18-24 years with
      athletes from various sports (e.g., swimming, soccer, basketball, tennis). A
      modified version of the quality assessment scale developed by Abernethy and
      Bleakley was used to evaluate the quality of the studies. RESULTS: The included
      studies implemented several sleep interventions, including sleep extension and
      napping, sleep hygiene, and post-exercise recovery strategies. Evidence suggests
      that sleep extension had the most beneficial effects on subsequent performance.
      Consistent with previous research, these results suggest that sleep plays an
      important role in some, but not all, aspects of athletes' performance and
      recovery. CONCLUSION: Future researchers should aim to conduct sleep
      interventions among different athlete populations, compare results, and further
      establish guidelines and intervention tools for athletes to address their
      specific sleep demands and disturbances.

PMID- 29352376
TI  - In reply: Is sugammadex alone enough to cause anaphylaxis?

PMID- 29352375
TI  - [Aspects of liaison psychiatry care of patients in a university pain clinic].
AB  - BACKGROUND: Owing to a rise of psychosomatic comorbidities, the treatment of
      psychological disorders, which may negatively impact prognosis and therapy, is
      increasingly becoming a focus of attention for pain outpatient clinics. AIM: This
      study investigates and discusses the advantages of liaison psychiatric care in a
      university pain clinic. METHODS: In this retrospective study, we investigated all
      patients who presented to an anaesthesiologically led pain clinic between January
      and June 2014. The psychiatric history was taken by the liaison psychiatrist of
      the pain clinic. RESULTS: In the period investigated, 485 patients were treated
      as outpatients. A psychiatric diagnosis was present 351 patients (72.4%). The
      distribution of the diagnoses was comparable with that of a consultation service.
      Adaptation and affective disorders dominated. The patients were preferentially
      treated with new generation antidepressants. CONCLUSION: The constant presence of
      a liaison psychiatrist allows for timely, specialised care of pain patients in
      terms of a multimodal therapeutic approach.

PMID- 29352377
TI  - Difference of acute dissociation and 1-day culture on the electrophysiological
      properties of rat dorsal root ganglion neurons.
AB  - The dissociated dorsal root ganglion (DRG) neurons with or without culture were
      widely used for investigation of their electrophysiological properties. The
      culture procedures, however, may alter the properties of these neurons and the
      effects are not clear. In the present study, we recorded the action potentials
      (AP) and the voltage-gated Na+, K+, and Ca2+ currents with patch clamp technique
      and measured the mRNA of Nav1.6-1.9 and Cav2.1-2.2 with real-time PCR technique
      from acutely dissociated and 1-day (1-d) cultured DRG neurons. The effects of the
      nerve growth factor (NGF) on the expression of Nav1.6-1.9 and Cav2.1-2.2 were
      evaluated. The neurons were classified as small (DRG-S), medium (DRG-M), and
      large (DRG-L), according to their size frequency distribution pattern. We found 1
      d culture increased the AP size but reduced the excitability, and reduced the
      voltage-gated Na+ and Ca2+ currents and their corresponding mRNA expression in
      all types of neurons. The lack of NGF in the culture medium may contribute to the
      reduced Na+ and Ca2+ current, as the application of NGF recovered some of the
      reduced transcripts (Nav1.9, Cav2.1, and Cav2.2). 1-d culture showed neuron-type
      specific effects on some of the AP properties: it increased the maximum AP
      depolarizing rate (MDR) and hyperpolarized the resting membrane potential (RP) in
      DRG-M and DRG-L neurons, but slowed the maximum AP repolarizing rate (MRR) in DRG
      S neurons. In conclusion, the 1-d cultured neurons had different properties with
      those of the acutely dissociated neurons, and lack of NGF may contribute to some
      of these differences.

PMID- 29352378
TI  - Can histogram analysis of MR images predict aggressiveness in pancreatic
      neuroendocrine tumors?
AB  - OBJECTIVES: To evaluate MRI derived whole-tumour histogram analysis parameters in
      predicting pancreatic neuroendocrine neoplasm (panNEN) grade and aggressiveness.
      METHODS: Pre-operative MR of 42 consecutive patients with panNEN >1 cm were
      retrospectively analysed. T1-/T2-weighted images and ADC maps were analysed.
      Histogram-derived parameters were compared to histopathological features using
      the Mann-Whitney U test. Diagnostic accuracy was assessed by ROC-AUC analysis;
      sensitivity and specificity were assessed for each histogram parameter. RESULTS:
      ADCentropy was significantly higher in G2-3 tumours with ROC-AUC 0.757;
      sensitivity and specificity were 83.3 % (95 % CI: 61.2-94.5) and 61.1 % (95 % CI:
      36.1-81.7). ADCkurtosis was higher in panNENs with vascular involvement, nodal
      and hepatic metastases (p= .008, .021 and .008; ROC-AUC= 0.820, 0.709 and 0.820);
      sensitivity and specificity were: 85.7/74.3 % (95 % CI: 42-99.2 /56.4-86.9),
      36.8/96.5 % (95 % CI: 17.2-61.4 /76-99.8) and 100/62.8 % (95 % CI: 56.1-100/44.9
      78.1). No significant differences between groups were found for other histogram
      derived parameters (p >.05). CONCLUSIONS: Whole-tumour histogram analysis of ADC
      maps may be helpful in predicting tumour grade, vascular involvement, nodal and
      liver metastases in panNENs. ADCentropy and ADCkurtosis are the most accurate
      parameters for identification of panNENs with malignant behaviour. KEY POINTS: *
      Whole-tumour ADC histogram analysis can predict aggressiveness in pancreatic
      neuroendocrine neoplasms. * ADC entropy and kurtosis are higher in aggressive
      tumours. * ADC histogram analysis can quantify tumour diffusion heterogeneity. *
      Non-invasive quantification of tumour heterogeneity can provide adjunctive
      information for prognostication.

PMID- 29352379
TI  - Magnetic resonance with diffusion-weighted imaging improves assessment of focal
      liver lesions in patients with potentially resectable pancreatic cancer on CT.
AB  - PURPOSE: To investigate added value of MRI to preoperative staging MDCT for
      evaluation of focal liver lesions (FLLs) in potentially resectable pancreatic
      ductal adenocarcinomas (PDACs). MATERIALS AND METHODS: In patients with
      potentially resectable PDACs after staging MDCT (n=167), characteristics of FLLs
      were scored as benign, indeterminate or metastases on an MDCT set and combined
      MDCT and MRI set by two readers, independently. Size of hepatic lesions was
      measured and detection rate of hepatic metastasis unsuspected by MDCT and
      diagnostic yield of MRI for FLLs were assessed. RESULTS: Reader-averaged figure
      of-merit (FOM) of the combined set was significantly higher than that of MDCT
      alone (0.94 vs. 0.86, p=.028). In the negative-on-CT group, the diagnostic yield
      of MRI was 1.5-2.3% (2/133 and 3/133 for readers 1 and 2, respectively). In the
      indeterminate-on-CT group, MRI yield was 10.5-13.6% (2/19 and 3/22) and in
      patients with suspicious-metastasis-on-CT, 8.3-26.7% (1/12 and 4/15). All lesions
      with false-positive and false-negative CT findings were <=1 cm. CONCLUSION: In
      potentially resectable PDACs, addition of MRI with DWI can provide significantly
      better diagnostic performance in characterization of focal liver lesions,
      especially for small-sized (<= 1 cm) MDCT-indeterminate or suspicious metastasis
      lesions, aiding in determination of appropriate operation candidates. KEY POINTS:
      * Addition of MRI provides better diagnostic performance in characterization of
      liver lesions. * Combined interpretation of MRI and MDCT provided less frequent
      indeterminate liver lesions. * Diagnostic yield of MRI was high in CT
      indeterminate or suspicious metastatic lesions. * Operation candidates can be
      determined with greater confidence in potentially resectable PDACs.

PMID- 29352380
TI  - Integrated prediction of lesion-specific ischaemia from quantitative coronary CT
      angiography using machine learning: a multicentre study.
AB  - OBJECTIVES: We aimed to investigate if lesion-specific ischaemia by invasive
      fractional flow reserve (FFR) can be predicted by an integrated machine learning
      (ML) ischaemia risk score from quantitative plaque measures from coronary
      computed tomography angiography (CTA). METHODS: In a multicentre trial of 254
      patients, CTA and invasive coronary angiography were performed, with FFR in 484
      vessels. CTA data sets were analysed by semi-automated software to quantify
      stenosis and non-calcified (NCP), low-density NCP (LD-NCP, < 30 HU), calcified
      and total plaque volumes, contrast density difference (CDD, maximum difference in
      luminal attenuation per unit area) and plaque length. ML integration included
      automated feature selection and model building from quantitative CTA with a
      boosted ensemble algorithm, and tenfold stratified cross-validation. RESULTS:
      Eighty patients had ischaemia by FFR (FFR <= 0.80) in 100 vessels. Information
      gain for predicting ischaemia was highest for CDD (0.172), followed by LD-NCP
      (0.125), NCP (0.097), and total plaque volumes (0.092). ML exhibited higher area
      under-the-curve (0.84) than individual CTA measures, including stenosis (0.76),
      LD-NCP volume (0.77), total plaque volume (0.74) and pre-test likelihood of
      coronary artery disease (CAD) (0.63); p < 0.006. CONCLUSIONS: Integrated ML
      ischaemia risk score improved the prediction of lesion-specific ischaemia by
      invasive FFR, over stenosis, plaque measures and pre-test likelihood of CAD. KEY
      POINTS: * Integrated ischaemia risk score improved prediction of ischaemia over
      quantitative plaque measures * Integrated ischaemia risk score showed higher
      prediction of ischaemia than standard approach * Contrast density difference had
      the highest information gain to identify lesion-specific ischaemia.

PMID- 29352381
TI  - Myocardial perfusion in patients with suspected coronary artery disease:
      comparison between 320-MDCT and rubidium-82 PET.
AB  - OBJECTIVES: Despite advances in non-invasive myocardial perfusion imaging (MPI)
      evaluation, computed tomography (CT) multiphase MPI protocols have not yet been
      compared with the highly accurate rubidium-82 positron emission tomography
      (82RbPET) MPI. Thus, this study aimed to evaluate agreement between 82RbPET and
      320-detector row CT (320-CT) MPI using a multiphase protocol in suspected CAD
      patients. METHODS: Forty-four patients referred for MPI evaluation were
      prospectively enrolled and underwent dipyridamole stress 82RbPET and multiphase
      320-CT MPI (five consecutive volumetric acquisitions during stress). Statistical
      analyses were performed using the R software. RESULTS: There was high agreement
      for recognizing summed stress scores >= 4 (kappa 0.77, 95% CI 0.55-0.98, p <
      0.001) and moderate for detecting SDS >= 2 (kappa 0.51, 95% CI 0.23-0.80, p <
      0.001). In a per segment analysis, agreement was high for the presence of
      perfusion defects during stress and rest (kappa 0.75 and 0.82, respectively) and
      was moderate for impairment severity (kappa 0.58 and 0.65, respectively). The 320
      CT protocol was safe, with low radiation burden (9.3 +/- 2.4 mSv). CONCLUSIONS:
      There was a significant agreement between dipyridamole stress 320-CT MPI and
      82RbPET MPI in the evaluation of suspected CAD patients of intermediate risk. The
      multiphase 320-CT MPI protocol was feasible, diagnostic and with relatively low
      radiation exposure. KEY POINTS: * Rubidium-82 PET and 320-MDCT can perform MPI
      studies for CAD investigation. * There is high agreement between rubidium-82 PET
      and 320-MDCT for MPI assessment. * Multiphase CT perfusion protocols are feasible
      and with low radiation. * Multiphase CT perfusion protocols can identify image
      artefacts.

PMID- 29352382
TI  - Hibernation of masses suspected to be remnant tumors after surgical resection of
      retroperitoneal liposarcoma is related to improved overall survival.
AB  - BACKGROUND: Although complete surgical resection is considered the best treatment
      for retroperitoneal liposarcoma, it is related to a high local recurrence rate.
      This study analyzed patterns of recurrence of retroperitoneal liposarcoma.
      METHODS: Records of patients who experienced recurrence after surgery for
      retroperitoneal liposarcoma from January 2000 to May 2017 were analyzed. Site,
      number, and characteristics of recurrent mass on computed tomography were
      serially collected. If a mass did not change size, it was considered a
      hibernating mass. Potential prognostic factors for overall survival were
      calculated using Kaplan-Meier survival log-rank tests. RESULTS: A total of 74
      patients, 28 within 6 months and 46 after 6 months, were detected as having a
      recurrence-suspected mass after surgery. Hibernation of a recurrence-suspected
      mass was found in 19 patients, 12 within 6 months and 7 after 6 months. While the
      presence of hibernation was not related to overall survival (P = 0.245), it was
      significantly related to improved survival in patients with a mass detected
      within 6 months (P = 0.022). Hibernation was not related to improved survival in
      patients with a mass detected after 6 months (P = 0.056). CONCLUSIONS:
      Hibernation of a recurrence-suspected mass was related to improvement of overall
      survival in patients with a mass detected within 6 months. This specific patient
      group should be monitored with care to see if the size of the mass increases.
      When a mass seemed to be hibernating, a favorable prognosis could be expected.

PMID- 29352384
TI  - Prenatal exposure to PCB and dioxin.

PMID- 29352383
TI  - Dietary patterns, their covariates, and associations with severity of depressive
      symptoms among university students in Lebanon: a cross-sectional study.
AB  - PURPOSE: The study aims to identify dietary patterns in university students in
      Lebanon, to determine their associations with socio-demographic, lifestyle, and
      stress factors, and to assess the link between identified dietary patterns and
      severity of depressive symptoms, controlling for multiple confounders. METHODS:
      Four hundred and fifty-seven private university students were surveyed.
      Information about dietary intake, socio-demographic and lifestyle factors,
      physical activity, and depressive symptoms were collected by the 73-item food
      frequency questionnaire, background questionnaire, International Physical
      Activity Questionnaire-Short Form, and Patient Health Questionnaire (PHQ-9),
      respectively. Dietary patterns were identified by exploratory factor analysis.
      Multiple linear regression analyses were conducted to (1) identify covariates
      that were independently associated with dietary patterns and (2) examine the
      independent associations between each of the dietary patterns and severity of
      depressive symptoms. RESULTS: Five dietary patterns were identified: "traditional
      Lebanese", "Western fast food", "dairy", "Lebanese fast food" and "fruits".
      Higher scores of traditional Lebanese and fruits patterns were found to be
      associated with more meals per day, frequent breakfast consumption, and non
      smoking. Higher Western fast food diet scores were shown to be associated with
      male gender, fewer meals per day, less frequent breakfast consumption, more
      frequent snacking, and alcohol consumption. Higher scores of the dairy pattern
      were found to be positively associated with hypertension, non-smoking, and
      frequency of alcohol consumption. Higher Lebanese fast food pattern scores were
      found to be associated with higher frequency of meal intake while watching TV and
      alcohol consumption. None of the five dietary patterns showed a significant
      association with severity of depressive symptoms after controlling for
      confounders. CONCLUSION: Severity of depressive symptoms showed no independent
      association with the identified dietary patterns.

PMID- 29352385
TI  - Outer Wall Segmentation of Abdominal Aortic Aneurysm by Variable Neighborhood
      Search Through Intensity and Gradient Spaces.
AB  - Aortic aneurysm segmentation remains a challenge. Manual segmentation is a time
      consuming process which is not practical for routine use. To address this
      limitation, several automated segmentation techniques for aortic aneurysm have
      been developed, such as edge detection-based methods, partial differential
      equation methods, and graph partitioning methods. However, automatic segmentation
      of aortic aneurysm is difficult due to high pixel similarity to adjacent tissue
      and a lack of color information in the medical image, preventing previous work
      from being applicable to difficult cases. This paper uses uses a variable
      neighborhood search that alternates between intensity-based and gradient-based
      segmentation techniques. By alternating between intensity and gradient spaces,
      the search can escape from local optima of each space. The experimental results
      demonstrate that the proposed method outperforms the other existing segmentation
      methods in the literature, based on measurements of dice similarity coefficient
      and jaccard similarity coefficient at the pixel level. In addition, it is shown
      to perform well for cases that are difficult to segment.

PMID- 29352386
TI  - Glucose homeostasis in major depression and schizophrenia: a comparison among
      drug-naive first-episode patients.
AB  - There is evidence for insulin resistance in drug-naive first-episode
      schizophrenia (Sz) patients. We have tested whether impaired insulin homeostasis
      is also present in first-episode patients with major depression (MD) and if this
      can be discerned from stress-related and medication effects. Homeostatic model
      assessment of insulin resistance (HOMA-IR) was determined in a cross-sectional
      cohort study of acute first-episode drug-naive patients with MD (n = 18) or Sz (n
      = 24), and healthy controls (C, n = 43). Morning cortisol and catecholamine
      metabolites were assessed to control for hormonal stress axis activation.
      Subjects were matched for sex, age, body mass index and waist-hip ratio to
      exclude the possibility that overweight and visceral adiposity were potential
      confounding factors. HOMA-IR did not differ between MD and controls, but was
      increased in Sz compared to MD (p = 0.002) and controls (p = 0.012).
      Catecholamine metabolites were elevated in both patient groups, indicating
      presence of hormonal stress axis activation. However, diagnosis-related changes
      of HOMA-IR were independent from this. Impaired insulin sensitivity was absent in
      MD, but specifically related to the early disease course of Sz. Thus, considering
      previous studies in this field, MD may be related to impaired glucose/insulin
      homeostasis in the long-term but not in early disease stages.

PMID- 29352387
TI  - Current Perspectives on Erythema Multiforme.
AB  - Recognition and timely adequate treatment of erythema multiforme remain a major
      challenge. In this review, current diagnostic guidelines, potential pitfalls, and
      modern/novel treatment options are summarized with the aim to help clinicians
      with diagnostic and therapeutic decision-making. The diagnosis of erythema
      multiforme, that has an acute, self-limiting course, is based on its typical
      clinical picture of targetoid erythematous lesions with predominant acral
      localization as well as histological findings. Clinically, erythema multiforme
      can be differentiated into isolated cutaneous and combined mucocutaneous forms.
      Atypical erythema multiforme manifestations include lichenoid or granulomatous
      lesions as well as lesional infiltrates of T cell lymphoma and histiocytes.
      Herpes simplex virus infection being the most common cause, other infectious
      agents like-especially in children-Mycoplasma pneumoniae, hepatitis C virus,
      Coxsackie virus, and Epstein Barr virus may also trigger erythema multiforme. The
      second most frequently identified cause of erythema multiforme is drugs. In
      different studies, e.g., allopurinol, phenobarbital, phenytoin, valproic acid,
      antibacterial sulfonamides, penicillins, erythromycin, nitrofurantoin,
      tetracyclines, chlormezanone, acetylsalicylic acid, statins, as well as different
      TNF-alpha inhibitors such as adalimumab, infliximab, and etanercept were reported
      as possible implicated drugs. Recently, cases of erythema multiforme associated
      with vaccination, immunotherapy for melanoma, and even with topical drugs like
      imiquimod have been described. In patients with recurrent herpes simplex virus
      associated erythema multiforme, the topical prophylactic treatment with acyclovir
      does not seem to prevent further episodes of erythema multiforme. In case of
      resistance to one virostatic drug, the switch to an alternative drug, and in
      patients non-responsive to virostatic agents, the use of dapsone as well as new
      treatment options, e.g., JAK-inhibitors or apremilast, might be considered.

PMID- 29352389
TI  - Detailed T1-Weighted Profiles from the Human Cortex Measured in Vivo at 3 Tesla
      MRI.
AB  - Studies into cortical thickness in psychiatric diseases based on T1-weighted MRI
      frequently report on aberrations in the cerebral cortex. Due to limitations in
      image resolution for studies conducted at conventional MRI field strengths (e.g.
      3 Tesla (T)) this information cannot be used to establish which of the cortical
      layers may be implicated. Here we propose a new analysis method that computes one
      high-resolution average cortical profile per brain region extracting
      myeloarchitectural information from T1-weighted MRI scans that are routinely
      acquired at a conventional field strength. To assess this new method, we acquired
      standard T1-weighted scans at 3 T and compared them with state-of-the-art ultra
      high resolution T1-weighted scans optimised for intracortical myelin contrast
      acquired at 7 T. Average cortical profiles were computed for seven different
      brain regions. Besides a qualitative comparison between the 3 T scans, 7 T scans,
      and results from literature, we tested if the results from dynamic time warping
      based clustering are similar for the cortical profiles computed from 7 T and 3 T
      data. In addition, we quantitatively compared cortical profiles computed for V1,
      V2 and V7 for both 7 T and 3 T data using a priori information on their relative
      myelin concentration. Although qualitative comparisons show that at an individual
      level average profiles computed for 7 T have more pronounced features than 3 T
      profiles the results from the quantitative analyses suggest that average cortical
      profiles computed from T1-weighted scans acquired at 3 T indeed contain
      myeloarchitectural information similar to profiles computed from the scans
      acquired at 7 T. The proposed method therefore provides a step forward to study
      cortical myeloarchitecture in vivo at conventional magnetic field strength both
      in health and disease.

PMID- 29352388
TI  - Cutaneous Granulomatosis: a Comprehensive Review.
AB  - Cutaneous granulomatosis is a heterogeneous group of diseases, characterized by a
      skin inflammatory reaction triggered by a wide variety of stimuli, including
      infections, foreign bodies, malignancy, metabolites, and chemicals. From a
      pathogenic point of view, they are divided into non-infectious and infectious
      granulomas. Pathophysiological mechanisms are still poorly understood. Non
      infectious granulomatous skin diseases include granuloma annulare, necrobiosis
      lipoidica, rheumatic nodules, foreign body granulomas, cutaneous sarcoidosis, and
      interstitial granulomatous dermatitis. Necrobiosis lipoidica is more frequent in
      diabetic patients. Infectious granulomas of the skin are caused by mycobacteria,
      in particular Mycobacterium tuberculosis or atypical mycobacteria; parasites,
      such as Leishmania; or fungi. Pathogenic mechanisms of M. tuberculosis-related
      granuloma are discussed. From a clinical point of view, it is useful to divide
      cutaneous granulomatosis into localized and more disseminated forms, although
      this distinction can be sometimes artificial. Three types of localized
      granulomatous lesions can be distinguished: palisaded granulomas (granuloma
      annulare, necrobiosis lipoidica, and rheumatoid nodules), foreign body
      granulomas, and infectious granulomas, which are generally associated with
      localized infections. Disseminated cutaneous granulomas can be divided into
      infectious, in particular tuberculosis, and non-infectious forms, among which
      sarcoidosis and interstitial granulomatous dermatitis. From a histological point
      of view, the common denominator is the presence of a granulomatous inflammatory
      infiltrate in the dermis and/or hypodermis; this infiltrate is mainly composed of
      macrophages grouped into nodules having a nodular, palisaded or interstitial
      architecture. Finally, we propose which diagnostic procedure should be performed
      when facing a patient with a suspected cutaneous granulomatosis.

PMID- 29352390
TI  - A Spatial Registration Toolbox for Structural MR Imaging of the Aging Brain.
AB  - During aging the brain undergoes a series of structural changes, in size, shape
      as well as tissue composition. In particular, cortical atrophy and ventricular
      enlargement are often present in the brain of elderly individuals. This poses
      serious challenges in the spatial registration of structural MR images. In this
      study, we addressed this open issue by proposing an enhanced framework for MR
      registration and segmentation. Our solution was compared with other approaches
      based on the tools available in SPM12, a widely used software package.
      Performance of the different methods was assessed on 229 T1-weighted images
      collected in healthy individuals, with age ranging between 55 and 90 years old.
      Our method showed a consistent improvement as compared to other solutions,
      especially for subjects with enlarged lateral ventricles. It also provided a
      superior inter-subject alignment in cortical regions, with the most marked
      improvement in the frontal lobe. We conclude that our method is a valid
      alternative to standard approaches based on SPM12, and is particularly suitable
      for the processing of structural MR images of brains with cortical atrophy and
      ventricular enlargement. The method is integrated in our software toolbox MRTool,
      which is freely available to the scientific community.

PMID- 29352391
TI  - Functional recovery by application of human dedifferentiated fat cells on
      cerebral infarction mice model.
AB  - Elderly people whose daily activities have declined due to a cerebrovascular
      disorder may suffer from dysphagia and may find oral hygiene difficult.
      Therefore, it is important to establish an effective therapy for the underlying
      cerebrovascular disorder. Dedifferentiated fat cells (DFAT) were obtained from
      mature adipocytes isolated from human buccal adipose pads in a ceiling culture.
      DFAT expressed the neural markers Nestin and SOX2. Flow cytometric analysis
      revealed that the cells had properties similar to mesenchymal stem cells.
      Although the transplantation of DFAT did not change the infarction area and
      volume ratios in a murine cerebral infarction model, functional recovery was
      observed in behavioral tests. Furthermore, DFAT administered to mice were later
      detected in cerebral infarctions. It therefore appears that transplanted DFAT
      affect the brain after infarction and contribute to the promotion of functional
      recovery. This finding may provide new cell replacement therapy options for
      treating disorders of the central nervous system.

PMID- 29352392
TI  - Impact of dexamethasone concentration on cartilage tissue formation from human
      synovial derived stem cells in vitro.
AB  - Human synovial mesenchymal stem cells (hSMSCs) are a promising cell source for
      cartilage regeneration because of their superior chondrogenic potential in vitro.
      This study aimed to further optimize the conditions for inducing chondrogenesis
      of hSMSCs, focusing on the dose of dexamethasone in combination with transforming
      growth factor-beta3 (TGFbeta3) and/or bone morphogenetic protein-2 (BMP2). When
      hSMSCs-derived aggregates were cultured with TGFbeta3, dexamethasone up to 10 nM
      promoted chondrogenesis, but attenuated it with heterogeneous tissue formation
      when used at concentrations over than 100 nM. On the other hands, BMP2-induced
      chondrogenesis was remarkably disturbed in the presence of more than 10 nM
      dexamethasone along with unexpected adipogenic differentiation. In the presence
      of both TGFbeta3 and BMP2, dexamethasone dose dependently promoted cartilaginous
      tissue formation as judged by tissue volume, proteoglycan content, and type 2
      collagen expression, whereas few adipocytes were detected in the formed tissue
      when cultures were supplemented with over 100 nM dexamethasone. Even in
      chondrogenic conditions, dexamethasone thus affected hSMSCs differentiation not
      only toward chondrocytes, but also towards adipocytes dependent on the dose and
      combined growth factor. These findings have important implications regarding the
      use of glucocorticoids in in vitro tissue engineering for cartilage regeneration
      using hSMSCs.

PMID- 29352394
TI  - Scarce evidence of ozone effect on recent health and productivity of alpine
      forests-a case study in Trentino, N. Italy.
AB  - We investigated the significance of tropospheric ozone as a factor explaining
      recent tree health (in terms of defoliation) and productivity (in terms of basal
      area increment, BAI) in 15 ICP Forests level I and one level II plots in alpine
      forests in Trentino (N. Italy). Mean daily ozone summer concentrations varied
      between 30 and 72 parts per billion (ppb) leading to large exceedance of
      concentration-based critical levels set to protect forest trees. Phytoxic ozone
      dose (POD0) estimated at the level II plot over the period 1996-2009 was 31-61
      mmol m-2 projected leaf area (PLA). The role of ozone was investigated taking
      into account other site and environmental factors. Simple linear regression,
      multiple linear regression (MLR, to study mean periodical defoliation and mean
      periodical BAI), and linear mixed models (LMM, to study annual defoliation data)
      were used. Our findings suggest that-regardless of the metric adopted
      tropospheric ozone is not a significant factor in explaining recent status and
      trends of defoliation and BAI in the alpine region examined. Both defoliation and
      BAI are in turn driven by biotic/abiotic damage, nutritional status, DBH (assumed
      as a proxy for age), and site characteristics. These results contrast with
      available ozone-growth dose response relationships (DRRs) and other observational
      studies. This may be due to a variety of concurrent reasons: (i) DRRs developed
      for individual saplings under controlled condition are not necessarily valid for
      population of mature trees into real forest ecosystems; (ii) some observational
      studies may have suffered from biased design; and (iii) since alpine forests have
      been exposed to high ozone levels (and other oxidative stress) over decades,
      possible acclimation mechanisms cannot be excluded.

PMID- 29352393
TI  - Eco-friendly pheromone dispensers-a green route to manage the European grapevine
      moth?
AB  - The development of environmentally sustainable control strategies to fight insect
      pests is a key challenge nowadays. Pheromone-mediated mating disruption (MD) is
      based on the release of synthetic sex attractants into a crop, interfering with
      mate finding of a given pest species. However, a limited number of research items
      have been published on the optimization of MD strategies against the European
      grapevine moth, Lobesia botrana, as well as on the use of biodegradable
      dispensers to reduce waste production in vineyards, despite the high economic
      importance of this pest. Therefore, the present study evaluated the efficacy of
      the MD products Isonet(r) L TT and the biodegradable Isonet(r) L TT BIO, applied
      at various densities, in reducing L. botrana damage on grapevine in comparison to
      an untreated control and the reference MD product Isonet(r) L. Experiments were
      conducted in three different areas of grapevine cultivation, located in Central
      and Northern Italy, over three different years. Our MD approach allowed a
      reliable control of the three generations of L. botrana during the whole grape
      growing season, leading to a significant reduction in the infested flower
      clusters and bunches, as well as in the number of nests per flower cluster and
      bunch, if compared to the untreated control. The performances of Isonet(r) L TT
      BIO, Isonet(r) LTT, and Isonet(r) L did not differ in terms of infested flower
      clusters/bunches, as well as nests per flower cluster/bunch. This was confirmed
      in all experimental sites over 3 years of field experiments. Overall, the present
      research provides useful information for the optimization of MD programs against
      L. botrana, highlighting the interesting potential of biodegradable pheromone
      dispensers that can be easily applied at low densities in vineyards, reducing the
      use of chemical pesticides to control moth pests.

PMID- 29352396
TI  - The Association Between the Intersection of Immigrant Status and Insurance with
      Adverse Birth Outcomes Among Mexican Women Residing in the San Joaquin Valley: A
      Mediation Analysis of Late Initiation or No Prenatal Care.
AB  - Latinos are the largest growing population and have the highest fertility rates
      in the US. In response, this study assessed if late initiation of or no prenatal
      care (PNC) mediated the relationship among adverse birth outcomes and
      interactions between immigrant and insurance status. This study used cross
      sectional data (2002-2004) limited to 109,399 women of Mexican ethnicity who had
      singleton births in the San Joaquin Valley, California. We conducted hierarchical
      mediation analyses. US-born Mexican women who used private or public insurance
      for PNC were more likely to have infants born at low-birth weight and premature
      compared to Mexican first generation immigrant women. Nonetheless, initiation of
      late or no PNC positively mediated the relationship between infants born
      premature to Mexican first generation immigrant women who used public insurance
      (ab/se(ab) = 2.123, p = .034). Findings from this study support acculturation
      theory and the need for multilevel approaches to address PNC among women of
      Mexican ethnicity.

PMID- 29352397
TI  - Bio-prospectus of cadmium bioadsorption by lactic acid bacteria to mitigate
      health and environmental impacts.
AB  - Foodstuffs and water are the key sources of cadmium biomagnifiaction. The
      available strategies to mitigate this problem are unproductive and expensive for
      practical large-scale use. Biological decontamination of metals through
      environmental microbes has been known since long time, whereas lactic acid
      bacteria (LAB) have not been extensively studied for this purpose. The LAB are
      known for maintaining homeostasis and suppression of pathogens in humans and
      animals. They also play a vital role in bioremediation of certain heavy metals.
      Recently in-vivo research findings strongly complement the in-vitro results in
      relation to decreased total body cadmium burden in animal model. This review
      summarizes the currently available information on impact of toxic metal (Cd) on
      human and animal health as well as cadmium sequestration through microbes placed
      broadly, whereas preeminent attention grabbed on LAB-cadmium interaction to
      explore their possible role in bioremediation of cadmium from foods and
      environment to safeguard human as well as environment health.

PMID- 29352395
TI  - Association between CRP genetic diversity and bipolar disorder comorbid
      complications.
AB  - BACKGROUND: Chronic low-grade inflammation is believed to contribute, at least in
      a subset of patients, to the development of bipolar disorder (BD). In this
      context, the most investigated biological marker is the acute phase response
      molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply
      studied in various pathological settings, little is known in BD. METHODS: 568 BD
      patients along with 163 healthy controls (HC) were genotyped for the following
      single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29)
      T/A, 3'-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The
      statistical analysis was performed using Chi-square testing and consisted of
      comparisons of allele/genotype frequencies between patients and controls and
      within patient sub-groups according to BD clinical phenotypes and the presence of
      thyroid disorders. RESULTS: We found that the frequencies of the studied SNPs
      were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier
      state was significantly more frequent: (i) in BD patients with thyroid disorders
      than in those without (pc = 0.046), especially among females (pc = 0.01) and
      independently of lithium treatment, (ii) in BD patients with rapid cycling than
      in those without (pc = 0.004). CONCLUSIONS: Overall, our findings suggest the
      possibility that CRP genetic diversity may contribute to the development of auto
      immune comorbid disorders and rapid cycling, both proxy of BD severity. Such
      findings, if replicated, may allow to predict complex clinical presentations of
      the disease, a possible step towards precision medicine in psychiatry.

PMID- 29352398
TI  - Efficient biosynthesis of L-phenylglycine by an engineered Escherichia coli with
      a tunable multi-enzyme-coordinate expression system.
AB  - Whole-cell catalysis with co-expression of two or more enzymes in a single host
      as a simple low-cost biosynthesis method has been widely studied and applied but
      hardly with regulation of multi-enzyme expression. Here we developed an efficient
      whole-cell catalyst for biosynthesis of L-phenylglycine (L-Phg) from
      benzoylformic acid through co-expression of leucine dehydrogenase from Bacillus
      cereus (BcLeuDH) and NAD+-dependent mutant formate dehydrogenase from Candida
      boidinii (CbFDHA10C) in Escherichia coli with tunable multi-enzyme-coordinate
      expression system. By co-expressing one to four copies of CbFDHA10C and
      optimization of the RBS sequence of BcLeuDH in the expression system, the ratio
      of BcLeuDH to CbFDH in E. coli BL21/pETDuet-rbs 4 leudh-3fdh A10C was finally
      regulated to 2:1, which was the optimal one determined by enzyme-catalyzed
      synthesis. The catalyst activity of E. coli BL21/pETDuet-rbs 4 leudh-3fdh A10C
      was 28.4 mg L-1 min-1 g-1 dry cell weight for L-Phg production using whole-cell
      transformation, it's was 3.7 times higher than that of engineered E. coli without
      enzyme expression regulation. Under optimum conditions (pH 8.0 and 35  degrees
      C), 60 g L-1 benzoylformic acid was completely converted to pure chiral L-Phg in
      4.5 h with 10 g L-1 dry cells and 50.4 g L-1 ammonium formate, and with
      enantiomeric excess > 99.9%. This multi-enzyme-coordinate expression system
      strategy significantly improved L-Phg productivity and demonstrated a novel low
      cost method for enantiopure L-Phg production.

PMID- 29352399
TI  - Predictors of Retention in an Alcohol and Risky Sex Prevention Program for
      Homeless Young Adults.
AB  - Homeless young adults are at risk for alcohol and other drug (AOD) use and risky
      sexual behavior. Interventions are needed to help these young people reduce their
      risky behavior, but this population is often difficult to engage and retain in
      services. We offered a four-session AOD and risky sex reduction program to 100
      participants and examined if retention in the program was predicted by a number
      of factors: demographics, homelessness severity, other service use, AOD
      behaviors, mental health symptoms, sexual risk behaviors, and readiness to change
      AOD and condom use. Nearly half (48%) of participants completed all sessions. In
      bivariate analyses, participants were significantly less likely to be retained in
      the program if they had slept outdoors in the past month, engaged in more alcohol
      and marijuana use, experienced more alcohol-related consequences, and received
      the program in an urban drop-in center (as opposed to a drop-in center near the
      beach). When controlling for all significant bivariate relationships, only
      sleeping outdoors and receipt of the program in the urban setting predicted fewer
      sessions completed. The most endorsed reasons for program non-completion were
      being too busy to attend and inconvenient day/time of the program. Findings can
      help outreach staff and researchers better prepare methods to engage higher risk
      homeless youth and retain them in services. Finding unique ways to help youth
      overcome barriers related to location of services appears especially necessary,
      perhaps by bringing services to youth where they temporarily reside or offering
      meaningful incentives for program attendance.

PMID- 29352400
TI  - Project Date SMART: a Dating Violence (DV) and Sexual Risk Prevention Program for
      Adolescent Girls with Prior DV Exposure.
AB  - : This study assessed the initial feasibility, acceptability, and efficacy of an
      intervention aimed at reducing dating violence and sexual risk behavior in a
      sample of adolescent girls (ages 14-17) with prior exposure to physical dating
      violence (DV). One hundred and nine girls were randomly assigned to Date SMART
      (Skills to Manage Aggression in Relationships for Teens) or a Knowledge-only (KO)
      comparison group. Both intervention arms consisted of six, weekly 2-h sessions
      and one "booster" session 6 weeks later. Based on principles of cognitive
      behavioral therapy, the Date SMART intervention was designed to target common
      underlying skills deficits linked to both DV and sexual risk behavior in
      adolescent females: depression, self-regulation deficits, and interpersonal
      skills deficits. Assessments were administered at four time points (baseline, 3,
      6, and 9 months). The Date SMART group was effective as reducing sexual DV
      involvement across the 9-month follow-up period. Both groups evidenced clinically
      meaningful reductions in physical, emotional, and digital DV involvement, total
      time in dating relationships, as well as reductions in depression. Findings
      indicate that delivering a DV and sexual risk prevention intervention to DV
      affected adolescent girls is feasible and well-received. Furthermore, a skills
      based approach that addresses the co-occurrence of DV and sexual risk behavior
      may be particularly useful for promoting reductions of sexual DV among high-risk
      adolescent girls. A future, large-scale trial with an inactive comparison
      condition is needed to evaluate the efficacy of Date SMART further. TRIAL
      REGISTRATION: Clinical Trials, NCT01326195, and http://www.clinicaltrials.gov.

PMID- 29352402
TI  - Erratum to: Accessory navicular bone: when ankle pain does not originate from the
      ankle.

PMID- 29352401
TI  - Does Giving Parents Their Choice of Interventions for Child Behavior Problems
      Improve Child Outcomes?
AB  - Empowering consumers to be active decision-makers in their own care is a core
      tenet of personalized, or precision medicine. Nonetheless, there is a dearth of
      research on intervention preferences in families seeking interventions for a
      child with behavior problems. Specifically, the evidence is inconclusive as to
      whether providing parents with choice of intervention improves child/youth
      outcomes (i.e., reduces externalizing problems). In this study, 129 families
      presenting to community mental health clinics for child conduct problems were
      enrolled in a doubly randomized preference study and initially randomized to
      choice or no-choice conditions. Families assigned to the choice condition were
      offered their choice of intervention from among three different formats of the
      Parent Management Training-Oregon Model/PMTO (group, individual clinic, home
      based) and services-as-usual (child-focused therapy). Those assigned to the no
      choice condition were again randomized, to one of the four intervention
      conditions. Intent-to-treat analyses revealed partial support for the effect of
      parental choice on child intervention outcomes. Assignment to the choice
      condition predicted teacher-reported improved child hyperactivity/inattention
      outcomes at 6 months post-treatment completion. No main effect of choice on
      parent reported child outcomes was found. Moderation analyses indicated that
      among parents who selected PMTO, teacher report of hyperactivity/inattention was
      significantly improved compared with parents selecting SAU, and compared with
      those assigned to PMTO within the no-choice condition. Contrary to hypotheses,
      teacher report of hyperactivity/inattention was also significantly improved for
      families assigned to SAU within the no-choice condition, indicating that within
      the no-choice condition, SAU outperformed the parenting interventions.
      Implications for prevention research are discussed.

PMID- 29352403
TI  - Micronized Zaleplon Delivery via Orodispersible Film and Orodispersible Tablets.
AB  - The following research study focuses on improving the solubility of zaleplon (BCS
      class II drug) via micronization technique in order to enhance its oral delivery
      in orodispersible formulations. Zaleplon along with a surfactant solution was
      micronized by ultrasonication. The micronization process reduced the particle
      size of the crystalline drug about six-fold from its original size of 155.5 MUm.
      The micronized zalepon dispersion was lyophilized to allow for a change in the
      state of matter (to a powder). The superior dissolution parameters (Q5, Q30, IDR,
      MDR, MDT, DE, and RDR) of zaleplon in microcrystalline form over the original
      crystalline form in in vitro dissolution studies had unraveled that micronization
      technique is an efficient tool in enhancing drug solubility. The micronized
      zaleplon solid dispersion (after lyophilization) was loaded into orodispersible
      tablet (ODT) and orodispersible film (ODF) formulations. The positive quality of
      ODT with adequate hardness and smooth texture was attributing to the presence of
      Pearlitol Flash(r) as a ready to use ODT platform. On the other hand, the ODF
      loaded with micronized zaleplon and prepared with Lycoat(r) RS 720 (as a film
      former) ensured adequate tensile strength. The disintegration time of ODT and ODF
      was 30 +/- 5 and 35 +/- 5 s, respectively. Thus, the orodispersible formulations
      containing micronized zaleplon have a strong potential for rapid disintegration
      following superior absorption in solution state through oral cavity into the
      blood stream, envisaging better oral delivery.

PMID- 29352404
TI  - Mechanisms Linking Obesity and Thyroid Cancer Development and Progression in
      Mouse Models.
AB  - Recent compelling epidemiological studies indicate a strong association of
      obesity with thyroid cancer. Obesity has been shown to promote thyroid cancer
      progression and exacerbate poor outcome in thyroid cancer patients. However, the
      molecular mechanisms by which obesity increases thyroid cancer risk and
      facilitates cancer progression are not completely understood. Obesity induces
      complex pathological changes including hyperglycemia, hyperinsulinemia,
      hyperlipidemia, oxidative stress, adipokines, and inflammatory responses. These
      changes can affect the development and progression of cancer through highly
      complex interactions in vivo. The deleterious effect of obesity may differ
      according to the different cancer types. In view of the increased incidence of
      thyroid cancer in parallel with the widespread occurrence of obesity in the past
      decades, it is imperative to clarify how obesity affects thyroid carcinogenesis.
      This review focuses on molecular mechanisms by which obesity aggravates thyroid
      carcinogenesis as elucidated by mouse models of thyroid cancer.

PMID- 29352405
TI  - Virus Particle Detection by Convolutional Neural Network in Transmission Electron
      Microscopy Images.
AB  - A new computational method for the detection of virus particles in transmission
      electron microscopy (TEM) images is presented. Our approach is to use a
      convolutional neural network that transforms a TEM image to a probabilistic map
      that indicates where virus particles exist in the image. Our proposed approach
      automatically and simultaneously learns both discriminative features and
      classifier for virus particle detection by machine learning, in contrast to
      existing methods that are based on handcrafted features that yield many false
      positives and require several postprocessing steps. The detection performance of
      the proposed method was assessed against a dataset of TEM images containing
      feline calicivirus particles and compared with several existing detection
      methods, and the state-of-the-art performance of the developed method for
      detecting virus was demonstrated. Since our method is based on supervised
      learning that requires both the input images and their corresponding annotations,
      it is basically used for detection of already-known viruses. However, the method
      is highly flexible, and the convolutional networks can adapt themselves to any
      virus particles by learning automatically from an annotated dataset.

PMID- 29352406
TI  - Does biopsy needle traversing through central portion of lesion increase the risk
      of hemoptysis during percutaneous transthoracic needle biopsy?
AB  - PURPOSE: To evaluate whether traversal through the central part of a pulmonary
      lesion by a biopsy needle, and other factors, increases the risk of hemoptysis in
      patients undergoing CT-guided percutaneous transthoracic needle biopsy (PTNB).
      MATERIALS AND METHODS: From July 2012 to November 2016, 227 patients undergoing
      233 procedures were recruited as our study population. Patients were classified
      according to the occurrence of hemoptysis. Radiological assessments were
      performed by reviewing multiplanar reconstructed CT images. Other factors
      complicating PTNB-related hemoptysis were classified into (1) patient-related
      variables: age, gender, presence of emphysema; (2) lesion-related variables:
      size, location, distance to pleura, characteristics, presence of and degree of
      enhancement, histopathology of biopsy results; and (3) procedure-related
      variables: lesion depth, patient's body position. RESULTS: Twenty-two cases
      (9.4%) experienced hemoptysis. Univariate analysis revealed that subsolid lesions
      (p = 0.031) and lesion depth > 1 cm (p = 0.049) were risk factors. Traversal
      through the central part of the lesion by the biopsy needle was not a risk
      factor. CONCLUSION: Traversal through the central part of the lesion by the
      biopsy needle is not a risk factor of PTNB-related hemoptysis, but subsolid
      lesions and lesion depth > 1 cm increase the risk of hemoptysis.

PMID- 29352407
TI  - [Rhegmatogenous retinal detachment : Epidemiology and risk factors].
AB  - The incidence of rhegmatogenous retinal detachment in the European population is
      approximately 10 cases per 100,000 inhabitants per year and reaches a peak in the
      6th and 7th decades of life, mostly in atemporal association with posterior
      vitreous body detachment. Known risk factors include myopia and higher axial
      length of the eye, male gender, previous trauma and vitreoretinal degeneration or
      dystrophy. In recent years, an increase in the risk of rhegmatogenous retinal
      detachment following cataract surgery was also found, especially after capsule
      rupture and vitreous body loss. In contrast to clear lens extraction (CLE), the
      refractive intervention of laser in situ keratomileusis (LASIK) does not seem to
      increase the risk of rhegmatogenous retinal detachment. Retinal detachment
      stabilizes during physical protection and posturing but progresses through bodily
      activity and during interruptions in patients with macula-on retinal detachment.

PMID- 29352408
TI  - [Placoid chorioretinal foci of inflammation in combination with prominent hili].

PMID- 29352410
TI  - First detection of murine herpesvirus 68 in adult Ixodes ricinus ticks.
AB  - Murine herpesvirus 68 (MHV-68) is a natural pathogen that infects murid rodents,
      which serves as hosts for Ixodes ricinus ticks. For the first time, MHV-68 was
      detected in immature I. ricinus ticks feeding on Lacerta viridis lizards trapped
      in Slovakia, which supports the idea that ticks can acquire the virus from
      feeding on infected hosts. The recent discovery of MHV-68 infection and MHV-68 M3
      gene transcripts in Dermacentor reticulatus ticks collected in Slovakia also
      supports this suggestion. Here, for the first time, we report MHV-68 infection,
      which was detected by nested PCR, in I. ricinus adults collected from the
      vegetation, and the viral load in infected ticks was determined by quantitative
      PCR. The viral incidence in ticks was 38.1% (21/55), and the viral load varied
      from 1.5 * 103 to 2.85 * 104 genome copies per tick. These results suggest that
      the I. ricinus ticks became infected with MHV-68 from biting infected rodents;
      thus, I. ricinus ticks may play a role in the spread of this virus in nature.

PMID- 29352411
TI  - The impact of using an upper-limb prosthesis on the perception of real and
      illusory weight differences.
AB  - Little is known about how human perception is affected using an upper-limb
      prosthesis. To shed light on this topic, we investigated how using an upper-limb
      prosthesis affects individuals' experience of object weight. First, we examined
      how a group of upper-limb amputee prosthetic users experienced real mass
      differences and illusory weight differences in the context of the 'size-weight'
      illusion. Surprisingly, the upper-limb prosthetic users reported a markedly
      smaller illusion than controls, despite equivalent perceptions of a real mass
      difference. Next, we replicated this dissociation between real and illusory
      weight perception in a group of nonamputees who lifted the stimuli with an upper
      limb myoelectric prosthetic simulator, again noting that the prosthetic users
      experienced illusory, but not real, weight differences as being weaker than
      controls. These findings not only validate the use of a prosthetic simulator as
      an effective tool for investigating perception and action but also highlight a
      surprising dissociation between the perception of real and illusory weight
      differences.

PMID- 29352409
TI  - Recent perspectives on the molecular basis of biofilm formation by Pseudomonas
      aeruginosa and approaches for treatment and biofilm dispersal.
AB  - Pseudomonas aeruginosa, a Gram-negative, rod-shaped bacterium causes widespread
      diseases in humans. This bacterium is frequently related to nosocomial infections
      such as pneumonia, urinary tract infections (UTIs) and bacteriaemia especially in
      immunocompromised patients. The current review focuses on the recent perspectives
      on biofilms formation by these bacteria. Biofilms are communities of
      microorganisms in which cells stick to each other and often adhere to a surface.
      These adherent cells are usually embedded within a self-produced matrix of
      extracellular polymeric substance (EPS). Pel, psl and alg operons present in P.
      aeruginosa are responsible for the biosynthesis of extracellular polysaccharide
      which plays an important role in cell surface interactions during biofilm
      formation. Recent studies suggested that cAMP signalling pathway, quorum-sensing
      pathway, Gac/Rsm pathway and c-di-GMP signalling pathway are the main mechanism
      that leads to the biofilm formation. Understanding the bacterial virulence
      depends on a number of cell-associated and extracellular factors and is very
      essential for the development of potential drug targets. Thus, the review focuses
      on the major genes involved in the biofilm formation, the state of art update on
      the biofilm treatment and the dispersal approaches such as targeting adhesion and
      maturation, targeting virulence factors and other strategies such as small
      molecule-based inhibitors, phytochemicals, bacteriophage therapy, photodynamic
      therapy, antimicrobial peptides and natural therapies and vaccines to curtail the
      biofilm formation by P. aeruginosa.

PMID- 29352412
TI  - Management regime is the most important factor influencing ectomycorrhizal
      species community in Norway spruce forests after windthrow.
AB  - Ectomycorrhizal (ECM) fungi, as symbionts of many tree species in temperate
      forests, are thought to play an important role in forest regeneration processes
      after large disturbances. Their reaction to different disturbance and management
      regimes was studied in spruce forests (Lariceto-Piceetum) 10 years after a severe
      windthrow in the Tatra National Park (Slovak Republic). ECM community structure
      was compared between different "management types"-cleared area (EXT), area
      affected by wildfire (FIRE), uncleared area left for natural development (NEX),
      and mature forest as a control (REF). Based on Illumina sequencing of soil
      samples, we determined that the percentage of sequences assigned to ECM fungi
      decreased with increasing disturbance and management intensity (REF -> NEX -> EXT
      -> FIRE). Similarly, the total number of ECM species per each of ten sampling
      points per plot (100 ha) differed between managed (EXT-11 species, FIRE-9) and
      unmanaged (NEX-16, REF-14) treatments. On the other hand, the percentage of
      sequences belonging to ericoid mycorrhizal fungi increased. Management type
      significantly influenced the composition of the ECM community, while vegetation
      and soil characteristics explained less data variation. The ECM species
      assemblage of the unmanaged site (NEX) was the most similar to the mature forest,
      while that of the burnt site was the most different. Thelephora terrestris
      dominated in all treatments affected by windthrow, accompanied by Tylospora
      fibrillosa (NEX) and Tylospora asterophora (EXT and FIRE). Management regime was
      also the most important factor affecting ECM species composition on the roots of
      spruce seedlings assessed by Sanger sequencing.

PMID- 29352414
TI  - Transthoracic echocardiographic evaluation of the heart and great vessels.
AB  - PURPOSE: Transthoracic examination of the heart and great vessels is an essential
      skill that allows the anesthesiologist to evaluate cardiac function. In this
      article, we describe a pragmatic technique to obtain the essential views to
      evaluate normal or abnormal cardiac function and to appreciate great vessel
      anatomy and physiology. PRINCIPAL FINDINGS: The cardiac anatomy and function can
      be described using standard parasternal, apical, and subcostal views. These
      windows can also be used to assess the aorta, pulmonary artery, and vena cavae;
      however, other transthoracic and abdominal windows can be used to complete the
      evaluation of the great vessels. CONCLUSIONS: The integration of the
      echocardiographic information particularly from the heart and great vessels with
      the case story, physical examination, laboratory data, and other relevant
      clinical information should become the way of the future, and this will benefit
      the patients under our care.

PMID- 29352415
TI  - Point-of-care ultrasound: a protean opportunity for perioperative care.

PMID- 29352416
TI  - Point-of-care ultrasound in pediatric anesthesiology and critical care medicine.
AB  - Ultrasound has increasingly become a clinical asset in the hands of the
      anesthesiologist and intensivist who cares for children. Though many applications
      for ultrasound parallel adult modalities, children as always are not simply small
      adults and benefit from the application of ultrasound to their management in
      various ways. Body composition and size are important factors that affect
      ultrasound performance in the child, as are the pathologies that may uniquely
      afflict children and aspects of procedures unique to this patient population.
      Ultrasound simplifies vascular access and other procedures by visualizing
      structures smaller than those in adults. Maturation of the thoracic cage presents
      challenges for the clinician performing pulmonary ultrasound though a greater
      proportion of the thorax can be seen. Moreover, ultrasound may provide unique
      solutions to sizing the airway and assessing it for cricothyroidotomy. Though
      cardiac ultrasound and neurosonology have historically been performed by well
      developed diagnostic imaging services, emerging literature stresses the utility
      of clinician ultrasound in screening for pathology and providing serial
      observations for monitoring clinical status. Use of ultrasound is growing in
      clinical areas where time and diagnostic accuracy are crucial. Implementation of
      ultrasound at the bedside will require institutional support of education and
      credentialing. It is only natural that the pediatric anesthesiologist and
      intensivist will lead the incorporation of ultrasound in the future practice of
      these specialties.

PMID- 29352417
TI  - Can we prevent significant brain desaturation during defibrillator testing by
      increasing the brain saturation reserve?

PMID- 29352418
TI  - Effect of Patient Experience on Bypassing a Primary Care Gatekeeper: a
      Multicenter Prospective Cohort Study in Japan.
AB  - BACKGROUND: To discuss how best to implement the gatekeeping functionality of
      primary care; identifying the factors that cause patients to bypass their primary
      care gatekeepers when seeking care should be beneficial. OBJECTIVE: To examine
      the association between patient experience with their primary care physicians and
      bypassing them to directly obtain care from higher-level healthcare facilities.
      DESIGN AND METHODS: This prospective cohort study was conducted in 13 primary
      care clinics in Japan. We assessed patient experience of primary care using the
      Japanese version of Primary Care Assessment Tool (JPCAT), which comprises six
      domains: first contact, longitudinality, coordination, comprehensiveness
      (services available), comprehensiveness (services provided), and community
      orientation. The primary outcome was the patient bypassing their usual primary
      care physician to seek care at a hospital, with this occurring at least once in a
      year. We used a Bayesian hierarchical model to adjust clustering within clinics
      and individual covariates. KEY RESULTS: Data were analyzed from 205 patients for
      whom a physician at a clinic served as their usual primary care physician. The
      patient follow-up rate was 80.1%. After adjustment for patients' sociodemographic
      and health status characteristics, the JPCAT total score was found to be
      inversely associated with patient bypass behavior (odds ratio per 1 SD increase,
      0.44; 95% credible interval, 0.21-0.88). The results of various sensitivity
      analyses were consistent with those of the primary analysis. CONCLUSIONS: We
      found that patient experience of primary care in Japan was inversely associated
      with bypassing a primary care gatekeeper to seek care at higher-level healthcare
      facilities, such as hospitals. Our findings suggest that primary care providers'
      efforts to improve patient experience should help to ensure appropriate use of
      healthcare services under loosely regulated gatekeeping systems; further studies
      are warranted.

PMID- 29352419
TI  - A Systematic Review of Interventions to Follow-Up Test Results Pending at
      Discharge.
AB  - BACKGROUND: Patients are frequently discharged from the hospital before all test
      results have been finalized. Thirty to 40% of tests pending at discharge (TPADs)
      return potentially actionable results that could necessitate change in the
      patients' management, often unbeknownst to their physicians. Delayed follow-up of
      TPADs can lead to patient harm. We sought to synthesize the existing literature
      on interventions intended to improve the management of TPADs, including
      interventions designed to enhance documentation of TPADs, increase physician
      awareness when TPAD results finalize post-discharge, decrease adverse events
      related to missed TPADs, and increase physician satisfaction with TPAD
      management. METHODS: We searched Medline, EMBASE, CINAHL, Cochrane Database of
      Systematic Reviews, Cochrane Database of Controlled Clinical Trials and Medline
      (January 1, 2000-November 10, 2016) for randomized controlled trials and
      prospective, controlled observational studies that evaluated interventions to
      improve follow-up of TPADs for adult patients discharged from acute care
      hospitals or emergency department settings. From each study we extracted
      characteristics of the intervention being evaluated and its impact on TPAD
      management. RESULTS: Nine studies met the criteria for inclusion. Six studies
      evaluated electronic discharge summary templates with a designated field for
      documenting TPADs, and three of six of these studies reported a significant
      improvement in documentation of TPADs in discharge summaries in pre- and post
      intervention analysis. One study reported that auditing discharge summaries and
      providing feedback to physicians were associated with improved TPAD documentation
      in discharge summaries. Two studies found that email alerts when TPADs were
      finalized improved physicians' awareness of the results and documentation of
      their follow-up actions. Of the four studies that assessed patient morbidity, two
      showed a positive effect; however, none specifically measured the impact of their
      interventions on downstream patient harm due to delayed follow-up of TPADs. Three
      studies surveyed physicians' attitudes towards the interventions, of which two
      studies reported improved physician satisfaction with TPAD management with the
      implementation of an enhanced discharge template and a notification system when
      TPADs finalize. DISCUSSION: Discharge summary templates, educational
      interventions for discharging physicians, and email alerts when TPAD results are
      finalized show promise in improving management of TPADs. Given the complexity of
      the processes necessary to ensure follow-up of TPADs, rigorous evaluations of
      multifaceted interventions (e.g., improved discharge documentation of TPADs
      combined with email alerts when results become available) is needed.

PMID- 29352420
TI  - Diagnosis and Management of Hepatitis C Infection in Primary Care Settings.
AB  - Hepatitis C virus (HCV) infection is a significant health problem worldwide, and
      is the leading cause of cirrhosis, hepatocellular carcinoma, and liver
      transplantation in the United States. The management of HCV has changed
      significantly over the last 5 years, as treatments have become simpler and more
      efficacious. Medication efficacy is now greater than 90%, with a high barrier to
      resistance and few side effects. This review is a collaboration between primary
      care and hepatology providers to explore all aspects of HCV management: acute
      versus chronic HCV infection, transmission and testing, and diagnosis and
      treatment. Specific medications for the treatment of HCV infection are
      considered, and patient and medication factors including genotype, liver disease
      status, and comorbidities affecting medication choice are discussed. This is a
      new era for the management of HCV infection, and interested primary care
      physicians, family doctors, and general internists can be at the forefront of
      diagnosis, management, and treatment of HCV.

PMID- 29352421
TI  - Predictors of Insulin Initiation in Patients with Type 2 Diabetes: An Analysis of
      the Look AHEAD Randomized Trial.
AB  - BACKGROUND: The decision to initiate insulin in patients with type 2 diabetes is
      a challenging escalation of care that requires an individualized approach.
      However, the sociodemographic and clinical factors affecting insulin initiation
      are not well understood. OBJECTIVE: We sought to identify patient factors that
      were independent predictors of insulin initiation among participants in the Look
      AHEAD (Action for Health in Diabetes) clinical trial. DESIGN: Retrospective
      analysis of a randomized clinical trial. PARTICIPANTS: Beginning in 2001, Look
      AHEAD enrolled ambulatory U.S. adults with type 2 diabetes who were overweight or
      obese and had a primary healthcare provider. Participants were randomized (1:1)
      to an intensive lifestyle intervention, or diabetes support and education. This
      study examined 3913 participants across the two trial arms who were not using
      insulin at baseline. MAIN MEASURES: We used Cox proportional hazards models to
      estimate the association between participant characteristics and time to insulin
      initiation. We performed time-varying adjustment for HbA1c measured eight times
      over the 10-year study period, as well as for multiple clinical and socioeconomic
      factors. KEY RESULTS: A total of 1087 participants (27.8%) initiated insulin
      during a median follow-up of 8.0 years. Age was inversely associated with insulin
      initiation (adjusted hazard ratio [aHR] 0.88 per 10 years, P = 0.025). The risk
      of insulin initiation was greater with a higher number of diabetes complications
      (P < 0.001 for trend); chronic kidney disease and cardiovascular disease were
      independently associated with insulin initiation. There was a lower risk of
      insulin initiation in black (aHR 0.77, P = 0.008) and Hispanic participants (aHR
      0.66, P < 0.001) relative to white participants. Socioeconomic factors were not
      associated with insulin initiation. CONCLUSIONS: Patient age, race/ethnicity, and
      diabetes complications may influence insulin initiation in type 2 diabetes,
      independent of glycemic control. Future work is needed to understand the drivers
      of racial differences in antihyperglycemic treatment, and to identify patients
      who benefit most from insulin.

PMID- 29352423
TI  - Understanding and Addressing Hair Disorders in Transgender Individuals.
AB  - In the United States, an increasing number of individuals are identifying as
      transgender. Males at birth who identify as females are called male-to-female
      (MTF) transgender individuals or trans women, and females at birth who identify
      as males are called female-to-male (FTM) transgender individuals or trans men.
      The transgender patient population possess unique health concerns disparate from
      those of the general populace. Exogenous hormone therapy for transgender patients
      leads to changes in the distribution and pattern of hair growth. Exogenous
      testosterone can lead to male pattern hair loss and hirsutism, while estrogen
      therapy usually results in decreased facial and body hair growth and density. A
      thorough understanding of the hormonal treatments that may be used in transgender
      individuals as well the unique and complex biologic characteristics of the hair
      follicle is required for appropriate diagnosis, counseling and treatment of
      patients. The aim of this article is to provide a framework for understanding
      hair disorders in transgender individuals and effective treatment options.

PMID- 29352424
TI  - Cannabinoid CB1 and CB2 Receptors, and Monoacylglycerol Lipase Gene Expression
      Alterations in the Basal Ganglia of Patients with Parkinson's Disease.
AB  - Previous studies suggest that the endocannabinoid system plays an important role
      in the neuropathological basis of Parkinson's disease (PD). This study was
      designed to detect potential alterations in the cannabinoid receptors CB1 (CB1r)
      and CB2 (A isoform, CB2Ar), and in monoacylglycerol lipase (MAGL) gene expression
      in the substantia nigra (SN) and putamen (PUT) of patients with PD.
      Immunohistochemical studies were performed to identify precise CB2r cellular
      localization in the SN of control and PD patients. To ensure the validity and
      reliability of gene expression data, the RNA integrity number (RIN) was
      calculated. CB1r, CB2Ar, and MAGL gene expressions were evaluated by real-time
      polymerase chain reaction (real-time PCR) using Taqman assays.
      Immunohistochemical experiments with in situ proximity ligation assay (PLA) were
      used to detect the precise cellular localization of CB2r in neurons, astrocytes,
      and/or microglia. All RIN values from control and PD postmortem brain samples
      were > 6. CB1r gene expression was unchanged in the SN but significantly higher
      in the PUT of patients with PD. CB2Ar gene expression was significantly increased
      (4-fold) in the SN but decreased in the PUT, whereas MAGL gene expression was
      decreased in the SN and increased in the PUT. Immunohistochemical analyses
      revealed that CB2r co-localize with astrocytes but not with neurons or microglial
      cells in the SN. The results of the present study suggest that CB1r, CB2r, and
      MAGL are closely related to the neuropathological processes of PD. Therefore, the
      pharmacological modulation of these targets could represent a new potential
      therapeutic tool for the management of PD.

PMID- 29352425
TI  - Safety and Efficacy of Nanocurcumin as Add-On Therapy to Riluzole in Patients
      With Amyotrophic Lateral Sclerosis: A Pilot Randomized Clinical Trial.
AB  - The objective of present study was to assess the safety and efficacy of
      nanocurcumin as an anti-inflammatory and antioxidant agent in adults with
      amyotrophic lateral sclerosis (ALS). We conducted a 12-month, double-blind,
      randomized, placebo-controlled trial at a neurological referral center in Iran.
      Eligible patients with a definite or probable ALS diagnosis were randomly
      assigned to receive either nanocurcumin (80 mg daily) or placebo in a 1:1 ratio.
      A computerized random number generator was used to prepare the randomization
      list. All patients and research investigators were blinded to treatment
      allocation. The primary outcome was survival, and event was defined to be death
      or mechanical ventilation dependency. Analysis was by intention-to-treat and
      included all patients who received at least one dose of study drug. A total of 54
      patients were randomized to receive either nanocurcumin (n = 27) or placebo (n =
      27). After 12 months, events occurred in 1 patient (3.7%) in the nanocurcumin
      group and in 6 patients (22.2%) in the placebo group. Kaplan-Meier analysis
      revealed a significant difference between the study groups regarding their
      survival curves (p = 0.036). No significant between-group differences were
      observed for any other outcome measures. No serious adverse events or treatment
      related deaths were detected. No patients withdrew as a result of drug adverse
      events. The results suggest that nanocurcumin is safe and might improve the
      probability of survival as an add-on treatment in patients with ALS, especially
      in those with existing bulbar symptoms. Future studies with larger sample sizes
      and of longer duration are needed to confirm these findings.

PMID- 29352426
TI  - Commentary to: "The Effects of Coenzyme Q10 Supplementation on Blood Pressures
      Among Patients with Metabolic Diseases: A Systematic Review and Meta-analysis of
      Randomized Controlled Trials".

PMID- 29352427
TI  - Preserved in vitro immunoreactivity in children receiving long-term
      immunosuppressive therapy due to inflammatory bowel disease or autoimmune
      hepatitis.
AB  - BACKGROUND: Children with inflammatory bowel disease (IBD) or autoimmune
      hepatitis (AIH) are at risk for severe infections. This is partially a result of
      their chronic disease condition but, moreover, a side effect of their
      immunosuppressive therapy. Currently, vaccinations with live vaccines are
      regarded as contraindicated under immunosuppressive therapy, mainly because of
      concerns about side effects and a lack of data showing an adequate immune
      reaction. As there is no systematic study on the individual immunoreactivity
      under immunosuppressive therapy in this patient group, we analyzed the lymphocyte
      subgroups and immunoreactivity of lymphocytes in children with IBD or AIH with
      and without immunosuppressive therapy in vitro. METHODS: We collected whole blood
      samples from 17 children with IBD or AIH on high-level immunosuppression (IS)
      (group 1) and 8 on low-level IS (group 2) in comparison with 6 patients without
      systemic IS (group 3). After Ficoll separation of peripheral mononuclear cells,
      the samples were analyzed by flow cytometry to determine the lymphocyte
      subgroups. Furthermore, we stimulated the isolated lymphocytes with
      phytohemagglutinin (PHA), tetanus antigen, and adenovirus antigen and measured
      their proliferation by incorporation of H3-thymidine detected in a beta counter.
      The statistical evaluation was performed by Kruskal-Wallis test and Mann-Whitney
      U test using a bilateral level of significance of alpha = 5%. RESULTS: Patients
      with low- or high-level IS showed no significant difference in the number of
      lymphocytes or T cells. Interestingly, IS did not influence the lymphocyte
      proliferation assay significantly regarding median reaction to PHA, tetanus
      antigen, or adenovirus antigen between the three groups. However, comparing all
      immunosuppressed patients to the patients without IS, there was a significant
      difference towards stimulation with tetanus antigen. CONCLUSIONS: Contrary to
      expectations of a strong influence of IS therapy on the immunoreactivity, this
      study showed only minor differences between the groups with high-level, low
      level, and no IS. Particularly, the in vitro reactivity to adenovirus antigen was
      nearly the same in all three groups. We assume that-provided a normal
      distribution and count of lymphocyte subgroups-patients with moderate
      immunosuppression might be capable of raising an effective immune response to
      inactivated and live vaccines.

PMID- 29352429
TI  - Deciphering the Environmental Impacts on Rice Quality for Different Rice
      Cultivated Areas.
AB  - BACKGROUND: Rice (Oryza sativa L.) is cultivated in a wide range of climatic
      conditions, and is one of mankind's major staple foods. The interaction of
      environmental factors with genotype effects major agronomic traits such as yield,
      quality, and resistance in rice. However, studies on the environmental factors
      affecting agronomic traits are often difficult to conduct because most
      environmental factors are dynamic and constantly changing. RESULTS: A series of
      recombinant inbred lines (RILs) derived from an indica/japonica cross were
      planted into four typical rice cultivated areas arranging from latitude N22
      degrees  to N42 degrees . The environmental data from the heading to mature (45
      days) stages were recorded for each RIL in the four areas. We determined that
      light, temperature, and humidity significantly affected the milling quality and
      cooking quality overall the four areas. Within each area, these environmental
      factors mainly affected the head rice ratio, grain length, alkali consumption,
      and amylose and protein content. Moreover, the effect of these environmental
      factors dynamically changed from heading to mature stage. Compared to light and
      humidity, temperature was more stable and predictable, and night temperature
      showed a stronger correlation efficiency to cooking quality than day temperature,
      and the daily temperature range had contrary effects compared to day and night
      temperature on grain quality. CONCLUSIONS: The present study evaluated the
      critical phase during the grain filling stage by calculating the dynamic changes
      of correlation efficiency between the quality traits and climate parameters. Our
      findings suggest that the sowing date could be adjusted to improve rice quality
      so as to adjust for environmental changes.

PMID- 29352428
TI  - Hnf4alpha is involved in the regulation of vertebrate LC-PUFA biosynthesis:
      insights into the regulatory role of Hnf4alpha on expression of liver fatty acyl
      desaturases in the marine teleost Siganus canaliculatus.
AB  - Long-chain polyunsaturated fatty acid (LC-PUFA) biosynthesis is an important
      metabolic pathway in vertebrates, especially fish, considering they are the major
      source of n-3 LC-PUFA in the human diet. However, most fish have only limited
      capability for biosynthesis of LC-PUFA. The rabbitfish (Siganus canaliculatus) is
      able to synthesize LC-PUFA as it has all the key enzyme activities required
      including Delta6Delta5 Fads2, Delta4 Fads2, Elovl5, and Elovl4. We previously
      reported a direct interaction between the transcription factor Hnf4alpha and the
      promoter regions of Delta4 and Delta6Delta5 Fads2, which suggested that Hnf4alpha
      was involved in the transcriptional regulation of fads2 in rabbitfish. For
      functionally investigating it further, a full-length cDNA of 1736-bp-encoding
      rabbitfish Hnf4alpha with 454 amino acids was cloned, which was highly expressed
      in intestine, followed by liver and eyes. Similar to the expression
      characteristics of its target genes Delta4 and Delta6Delta5 fads2, levels of
      hnf4alpha mRNA in liver and eyes were higher in fish reared at low salinity than
      those reared in high salinity. After the rabbitfish primary hepatocytes were,
      respectively, incubated with alverine, benfluorex or BI6015, which were
      anticipated agonists or antagonist for Hnf4alpha, the mRNA level of Delta6Delta5
      and Delta4 fads2 displayed a similar change tendency with that of hnf4alpha mRNA.
      Furthermore, when the mRNA level of hhf4alpha was knocked down using siRNA, the
      expression of Delta6Delta5 and Delta4 fads2 also decreased. Together, these data
      suggest that Hnf4alpha is involved in the transcriptional regulation of LC-PUFA
      biosynthesis, specifically, by targeting Delta4 and Delta6Delta5 fads2 in
      rabbitfish.

PMID- 29352430
TI  - Correction to: Clinical Surveillance After Macroscopically Complete Surgery for
      Low-Grade Appendiceal Mucinous Neoplasms (LAMN) with or Without Limited
      Peritoneal Spread: Long-Term Results in a Prospective Series.
AB  - In the original article Massimo Milione's last name was spelled incorrectly. It
      is correct as reflected here. The original article has also been updated.

PMID- 29352431
TI  - Analysis and Comparison of the 8th Edition American Joint Committee on Cancer
      (AJCC) Nodal Staging System in Cutaneous and Oral Squamous Cell Cancer of the
      Head and Neck.
AB  - BACKGROUND: The American Joint Committee on Cancer (AJCC) uses the same nodal
      staging system for cutaneous and mucosal squamous cell carcinoma of the head and
      neck in its 8th edition (AJCC 8) despite differences in the etiology, risk
      factors, and clinical behavior of the two diseases. This study aims to evaluate
      the performance of the AJCC 8 nodal staging system by direct comparison of
      cutaneous (cSCC) versus oral squamous cell carcinoma (oSCC) patients. METHODS:
      Patients with metastatic cSCC (N = 382) and oSCC (N = 325) were identified from a
      prospective database (years 1987-2016). Multivariable analysis was performed
      using Cox proportional hazards competing risk model. To assess staging system
      performance, an explained variation measure (proportion of variation explained,
      PVE) as well as a discrimination measure (Harrell's concordance index, C-index)
      were used. RESULTS: Inclusion of extranodal extension (ENE) in AJCC 8 increased
      the proportion of patients in N3b category (48.7% in cSCC, 40.3% in oSCC). AJCC 8
      stratified poorly with regards to risk of death from cSCC and oSCC and showed
      limited monotonicity of the nodal categories. Estimates of model performance
      revealed modest predictive capacity for overall survival (OS) and disease
      specific survival (DSS) in oSCC (Harrell's C of 0.66 in both) and weak predictive
      capacity in cSCC (Harrell's C of 0.58 and 0.61, respectively). CONCLUSIONS: The
      AJCC 8 nodal staging system performs poorly in terms of stratifying survival by N
      category, especially in cSCC. The data indicate that cSCC merits an independent
      nodal staging system from that for mucosal SCC.

PMID- 29352432
TI  - Effect of Membrane Composition on Receptor Association: Implications of Cancer
      Lipidomics on ErbB Receptors.
AB  - The association of single transmembrane receptors, such as the ErbB receptors is
      a key event in initiating cell signaling networks. The interactions between these
      receptors have been well characterized for both ligand-driven and pre-formed
      dimers. However, the role of the membrane in modulating association is less well
      understood and assumes greater importance in light of altered membrane
      composition in diseased states. Here, we discuss how membrane composition has
      been observed to induce both structural and dynamic differences in receptor
      association. Computational studies, especially those using coarse-grain
      simulations have been successful in predicting the role of the membrane and
      calculating the related free energy landscapes. Membrane perturbations and
      differences in lipid chain order, related to the lipophobic effect, have been
      shown to play a large role in driving membrane protein association. Further, we
      review lipid compositions reported in diseased conditions and its effect on
      transmembrane receptor association, focusing on the ErbB growth factor receptor
      dimers in cancer. Understanding the role of the membrane in receptor association
      will provide general design principles driving receptor organization, as well as
      help to identify novel therapeutic strategies.

PMID- 29352433
TI  - Development and clinical application of Vertebral Metrics: using a stereo vision
      system to assess the spine.
AB  - The biomechanical changes in the spinal column are considered to be the main
      responsible for rachialgia. Although radiological techniques use ionizing
      radiation, they are the most applied tools to assess the biomechanics of the
      spine. To face this problem, non-invasive techniques must be developed. Vertebral
      Metrics is an ionizing radiation-free instrument designed to detect the 3D
      position of each vertebrae in a standing position. Using a stereo vision system
      combined with low intensity UV light, recognition is achieved with software
      capable of distinguishing fluorescent marks. The fluorescent marks are the skin
      projection of the vertex of the spinal processes. This paper presents a major
      development of Vertebral Metrics and its evaluation. It performs a scan in less
      than 45 s with a resolution on the order of 1 mm, in each spatial direction,
      therefore, allowing an accurate analysis of the spine. The instrument was applied
      to patients without associated pathology. Statistically significant differences
      between consecutive scans were not found. A positive correlation between the 3D
      positions of each vertebra and the homologous position of the other vertebrae was
      observed. Using Vertebral Metrics, innovative results can be obtained. It can be
      used in areas such as orthopedics, neurosurgery, and rehabilitation. Graphical
      abstract ?.

PMID- 29352434
TI  - Author Correction to: Gene Patents in Canada: Is There a New Legal Landscape?
AB  - An error was subsequently identified in the article, and the following correction
      should be noted.

PMID- 29352435
TI  - Outcome of hip and knee periprosthetic joint infections caused by pathogens
      resistant to biofilm-active antibiotics: results from a prospective cohort study.
AB  - BACKGROUND: Periprosthetic joint infections (PJI) caused by pathogens, for which
      no biofilm-active antibiotics are available, are often referred to as difficult
      to-treat (DTT). However, it is unclear whether the outcome of DTT PJI is worse
      than those of non-DTT PJI. We evaluated the outcome of DTT and non-DTT PJI in a
      prospective cohort treated with a two-stage exchange according to a standardized
      algorithm. METHODS: Patients with hip and knee PJI from 2013 to 2015 were
      prospectively included and followed up for >= 2 years. DTT PJI was defined as
      growth of microorganism(s) resistant to all available biofilm-active antibiotics.
      The Kaplan-Meier survival analysis was used to compare the probability of
      infection-free survival between DTT and non-DTT PJI and the 95% confidence
      interval (95% CI) was calculated. RESULTS: Among 163 PJI, 30 (18.4%) were
      classified as DTT and 133 (81.6%) as non-DTT. At a mean follow-up of 33 months
      (range 24-48 months), the overall treatment success was 82.8%. The infection-free
      survival rate at 2 years was 80% (95% CI 61-90%) for DTT PJI and 84% (95% CI 76
      89%) for non-DTT PJI (p = 0.61). The following mean values were longer in DTT PJI
      than in non-DTT PJI: hospital stay (45 vs. 28 days; p < 0.001), prosthesis-free
      interval (89 vs. 58 days; p < 0.001) and duration of antimicrobial treatment (151
      vs. 117 days; p = 0.003). CONCLUSIONS: The outcome of DTT and non-DTT PJI was
      similar (80-84%), however, at the cost of longer hospital stay, longer prosthesis
      free interval and longer antimicrobial treatment. It remains unclear whether
      patients undergoing two-stage exchange with a long interval need biofilm-active
      antibiotics. Further studies need to evaluate the outcome in patients treated
      with biofilm-active antibiotics undergoing short vs. long interval.

PMID- 29352436
TI  - Posterolateral tibial plateau fractures, how to buttress? Reversed L
      posteromedial or the posterolateral approach: a comparative cadaveric study.
AB  - INTRODUCTION: The selection of a surgical approach for buttressing posterolateral
      tibial plateau fractures is controversial. OBJECTIVE: This study compared the
      surgical exposure area between the reversed L posteromedial approach (R-PM) and
      the posterolateral (PL) approach using the lateral plateau width as a metric.
      MATERIALS AND METHODS: Twenty lower extremities from fresh frozen cadavers were
      included. The R-PM approach was used first and the boundary of the posterior
      tibial cortex exposure was marked with metal pins. With the same specimens, the
      PL approach was then performed and the exposure area was marked. After removing
      all soft tissue, an imaginary line was drawn from the lateral plateau rim
      anterior to the fibular head (L) to the posteromedial ridge of the tibia (M).
      Additional metal pins were used to indicate bony reference landmarks at the joint
      line on the posterior tibial plateau, including the lateral tibial spine (S), the
      lateral boundary with the PM approach (LPM) and the lateral boundary with the PL
      approach (LPL). All distances were measured using S as the reference point.
      RESULTS: The average distance from S to L, referred to as the lateral plateau
      width (A), was 32.62 mm. The average distances from S to LPM (B) and from S to
      LPL measured as a percentage of A were 43.72 and 81.41%, respectively. The
      average R-PM approach blind distance from LPM to LPL (C) as a percentage of the
      lateral plateau width was 58.45%, while the distance LPL to L (D), which
      represents the invisible blind distance with both approaches, was 15.37% of that
      width. CONCLUSIONS: The PL approach provides better access for buttressing the
      posterolateral tibial plateau fracture than the R-PM approach. With the R-PM
      approach, the blind area on the lateral plateau which can be accessed only by the
      PL approach starts approximately at 43.72% and ends at 81.41% of the lateral
      tibial plateau width. When a fracture is located in this zone, the posterolateral
      approach is recommended.

PMID- 29352437
TI  - Cost Effectiveness of Treatments for Chronic Constipation: A Systematic Review.
AB  - BACKGROUND: Chronic constipation (CC) has a significant impact on patients'
      quality of life and imposes an economic burden on individuals and the healthcare
      system. Treatment options include dietary changes, lifestyle modifications, fibre
      supplements, stool softeners, and laxatives. OBJECTIVE: We undertook this
      systematic review to comprehensively evaluate the cost effectiveness of
      treatments for CC. METHODS: We searched ten common databases to identify economic
      evaluations published to 13 June 2017. Abstract and full-text review were
      completed in duplicate. The quality of the included studies was assessed using
      the Consensus on Health Economic Criteria. Data extracted included costs and
      outcomes of treatments for CC and cost-effectiveness methods. A narrative
      synthesis was completed. RESULTS: From the 4338 unique citations identified, 79
      proceeded to full-text review, with 10 studies forming the final dataset. Eight
      different definitions of CC were used to define the study populations. Study
      designs used were decision-tree models (4), Markov model (1), and retrospective
      (1) and prospective (4) studies. Quality-adjusted life-years (QALY) were reported
      in five studies; other outcomes included, discontinuation of laxative treatment
      and frequency of bowel movements. The majority of studies stated that their
      results were from a payer perspective; however, some of these studies only
      considered treatment costs, a subset of costs included in the payer perspective.
      Lifestyle advice, dietary treatments and abdominal massage were each compared
      with current care with laxatives, while polyethylene glycol (PEG) and senna-fibre
      combination were each compared with lactulose. Two studies compared newer
      treatments in patients who had not responded to laxatives: prucalopride was
      compared with continuing laxatives, and linaclotide was compared with
      lubiprostone. All of the interventions were reported by the study authors to be
      cost effective, with the exception of abdominal massage. CONCLUSIONS: A
      consistent definition of CC is needed and the QALY should be used to capture the
      diverse symptoms of CC. Further analysis is needed comparing all available
      treatments for patients who have not responded to laxatives. Overall, results
      from economic evaluations appear to align with stepwise practice guidelines.

PMID- 29352438
TI  - The Art of Innovation: an Interview with Yuman Fong, MD.

PMID- 29352439
TI  - Single-Incision Laparoscopic Transgastric Underrunning and Closure of Cameron
      Ulcers in Acute Gastrointestinal Bleeding.
AB  - INTRODUCTION: Endoscopic therapy remains the cornerstone of hemostasis for
      gastrointestinal bleeding. In situations where hemostasis cannot be achieved via
      endoscopic or radiological methods, surgery is necessary. Traditional open
      surgery for bleeding gastric ulcers can be very morbid and unsuitable especially
      in hemodynamically unstable patients in extremis. We describe a minimally
      invasive, transgastric approach for underrunning and closure of Cameron ulcers.
      METHODS: Our patient is a 75-year-old Chinese lady, who presented to the
      emergency department with fresh melena. She was hemodynamically unstable with
      severe metabolic acidosis. CT angiography revealed blood clots within the
      stomach, with no active blush. On urgent gastroscopy, large blood clots obscured
      the site of hemorrhage. A Mallory-Weiss tear was noted. Our patient subsequently
      underwent a successful single-incision laparoscopic transgastric (SLT)
      underrunning and closure of two Cameron ulcers. RESULTS: Our patient had an
      uneventful recovery and subsequently underwent a successful laparoscopic para
      esophageal hernia repair on postoperative day 9. CONCLUSION: A SLT approach is a
      suitable minimally invasive option for the surgical management of hemostasis and
      closure of bleeding gastric ulcers not amenable to endoscopic or radiological
      interventions.

PMID- 29352440
TI  - The Limitations of Standard Clinicopathologic Features to Accurately Risk
      Stratify Prognosis after Resection of Intrahepatic Cholangiocarcinoma.
AB  - BACKGROUND: The ability to provide accurate prognostic data after hepatectomy for
      intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and
      validate a nomogram to predict survival, as well as investigate the clinical
      implications of underestimating patients' risk of recurrence. METHODS: Patients
      undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major
      hepatobiliary centers were included. Variables significant on multivariable
      analysis were used to construct a nomogram to predict disease-free survival
      (DFS). The nomogram assigned a score to each variable included in the model and
      calculated the risk of recurrence. RESULTS: Eight hundred ninety-seven patients
      are included in the analytic cohort. On multivariable Cox regression analysis,
      tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR
      1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25
      2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p
      < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09
      1.83; p = 0.008) were independent adverse risk factors associated with decreased
      DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000
      bootstrapping resamples) and the plot comparing predicted and actuarial DFS
      demonstrated a good calibration of the model. A subset of patients (n = 282) had
      a DFS worse than predicted (DeltaPredicted DFS - Actuarial DFS > 6 months).
      Moreover, underestimation of a recurrence risk was more common among patients
      with clinicopathologic features traditionally considered "favorable." CONCLUSION:
      A nomogram based on standard clinicopathologic characteristics was suboptimal in
      its ability to predict accurately risk of recurrence among patients with ICC
      after curative-intent liver resection. Particularly, the risk of underestimating
      patient risk of recurrence was highest among patients with historically favorable
      characteristics. Over one third of patients recurred > 6 months earlier than the
      DFS predicted by the nomogram.

PMID- 29352442
TI  - Laparoscopic and Endoscopic Cooperative Surgery Versus Endoscopic Submucosal
      Dissection for the Treatment of Low-Risk Tumors of the Duodenum.
AB  - BACKGROUND: There have been no comparative studies of endoscopic submucosal
      dissection (ESD) and laparoscopic and endoscopic cooperative surgery (LECS) for
      patients with duodenal tumors regarding surgical outcomes. The aim of this study
      is to compare the safety and feasibility of short-term surgical outcomes of ESD
      and LECS for patients with low-risk tumors of the duodenum. METHODS: This was a
      single-center retrospective study of 68 consecutive patients with low-risk tumors
      of the duodenum who received surgical treatments. ESD (n = 50) was performed
      between 2000 and 2013 and LECS (n = 18) was performed between 2014 and 2017.
      RESULTS: The overall incidence of perioperative complications was significantly
      higher in the ESD group (28%) than in the LECS group (0%) (P = 0.014). In the ESD
      group, eight patients with intraoperative perforation of duodenum (16%) were
      repaired with metal clips. Postoperative duodenal hemorrhage occurred in three
      patients (6%). Postoperative duodenal stricture requiring endoscopically guided
      balloon dilation was observed in two patients (4%). Postoperative bile leakage
      was found in one patient (2%). The size of resected lesion was significantly
      larger in the LECS group (26.5 mm) than in the ESD group (14.5 mm) (P = 0.003).
      In LECS group, all 18 patients underwent curative resection; however, the
      curative resection rate was 52% in ESD group (P = 0.001). CONCLUSION: LECS for
      patients with low-risk tumors of the duodenum is a safe, feasible, and ideal
      alternative to ESD with regard to short-term surgical outcomes. TRIAL
      REGISTRATION: UMIN000021200 ( http://www.umin.ac.jp/ctr/ ).

PMID- 29352441
TI  - Utility of Tumor Burden Score to Stratify Prognosis of Patients with
      Hepatocellular Cancer: Results of 4759 Cases from ITA.LI.CA Study Group.
AB  - BACKGROUND: Dichotomous models like Milan Criteria represent the routinely used
      tools for predicting the outcome of patients with hepatocellular carcinoma (HCC).
      However, a paradigm shift from a dichotomous to continuous prognostic
      stratification should represent a good strategy for improving the prediction
      process. Recently, the tumor burden score (TBS) has been proposed for selecting
      patients with colorectal liver metastases. To date, TBS has not been validated in
      a large HCC population. The main objective of this study was to evaluate the
      prognostic power of TBS in an HCC population treated with different curative and
      palliative modalities. METHODS: Prospectively collected data from consecutive HCC
      patients managed in 24 institutions participating in the ITA.LI.CA group between
      Jan 2002 and Mar 2015 were analyzed (n = 4759). A sub-analysis focused on 3909
      patients with the radiological evidence of vascular invasion or metastatic
      disease was also performed. RESULTS: TBS demonstrated the best discriminative
      ability when compared to MC and other tumor-specific scores. At multivariable Cox
      regression analysis, TBS was an independent risk factor of overall survival, with
      a 6% increased risk for patient death for each point increase in TBS. At survival
      analysis, when TBS >= 8 was connected with MELD >= 15 and alpha-fetoprotein >=
      1000 ng/mL, patients presenting all these three risk factors presented the worst
      results (p value < 0.0001). CONCLUSIONS: Survival prediction of HCC patients was
      very well done using TBS model, even stratifying the population in relation to
      the presence of metastases and/or vascular invasion. TBS model was the best in
      terms of discriminatory ability and goodness of fit when compared with other
      continuous or binary variables. Its incorporation in a model composed by tumor-
      and liver function-related variables further increases its survival prediction.

PMID- 29352443
TI  - Baculovirus-based gene silencing of Humanin for the treatment of pituitary
      tumors.
AB  - Pituitary tumors are the most common primary intracranial neoplasms. Humanin (HN)
      and Rattin (HNr), a rat homolog of HN, are short peptides with a cytoprotective
      action. In the present study, we aimed to evaluate whether endogenous HNr plays
      an antiapoptotic role in pituitary tumor cells. Thus, we used RNA interference
      based on short-hairpin RNA (shRNA) targeted to HNr (shHNr). A plasmid including
      the coding sequences for shHNr and dTomato fluorescent reporter gene was
      developed (pUC-shHNr). Transfection of somatolactotrope GH3 cells with pUC-shHNr
      increased apoptosis, suggesting that endogenous HNr plays a cytoprotective role
      in pituitary tumor cells. In order to evaluate the effect of blockade of
      endogenous HNr expression in vivo, we constructed a recombinant baculovirus (BV)
      encoding shHNr (BV-shHNr). In vitro, BV-shRNA was capable of transducing more
      than 80% of GH3 cells and decreased HNr mRNA. Also, BV-shHNr increased apoptosis
      in transduced GH3 cells. Intratumor injection of BV-shHNr to nude mice bearing
      s.c. GH3 tumors increased the number of apoptotic cells, delayed tumor growth and
      enhanced survival rate, suggesting that endogenous HNr may be involved in
      pituitary tumor progression. These preclinical data suggests that the silencing
      of HN expression could have a therapeutic impact on the treatment of pituitary
      tumors.

PMID- 29352444
TI  - Activation of the Anti-Aging and Cognition-Enhancing Gene Klotho by CRISPR-dCas9
      Transcriptional Effector Complex.
AB  - Multiple lines of evidence show that the anti-aging and cognition-enhancing
      protein Klotho fosters neuronal survival, increases the anti-oxidative stress
      defense, and promotes remyelination of demyelinated axons. Thus, upregulation of
      the Klotho gene can potentially alleviate the symptoms and/or prevent the
      progression of age-associated neurodegenerative diseases such as Alzheimer's
      disease and demyelinating diseases such as multiple sclerosis. Here we used a
      CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho
      promoter region for efficient transcriptional activation of the Klotho gene. We
      tested the sgRNAs within the - 1 to - 300 bp of the Klotho promoter region and
      identified two sgRNAs that can effectively enhance Klotho gene transcription. We
      examined the transcriptional activation of the Klotho gene using three different
      systems: a Firefly luciferase (FLuc) and NanoLuc luciferase (NLuc) coincidence
      reporter system, a NLuc knock-in in Klotho 3'-UTR using CRISPR genomic editing,
      and two human cell lines: neuronal SY5Y cells and kidney HK-2 cells that express
      Klotho endogenously. The two sgRNAs enhanced Klotho expression at both the gene
      and protein levels. Our results show the feasibility of gene therapy for
      targeting Klotho using CRISPR technology. Enhancing Klotho levels has a
      therapeutic potential for increasing cognition and treating age-associated
      neurodegenerative, demyelinating and other diseases, such as chronic kidney
      disease and cancer.

PMID- 29352445
TI  - Effect of Sevoflurane Anesthesia on Brain Is Mediated by lncRNA HOTAIR.
AB  - Postoperative cognitive dysfunction in elderly patients has been related to
      neurodegenerative disorders and mortality. Sevoflurane anesthesia has been
      implicated in both postoperative cognitive dysfunction and neurotoxicity. Given
      the advantages of using inhaled anesthetics like sevoflurane, it is important to
      understand how their usage results in neurotoxicity and subsequently devise ways
      to circumvent or attenuate the anesthetic-mediated induction in neurotoxicity.
      Long noncoding RNAs (LncRNAs) are a group of > 200 bp long RNAs and show specific
      spatiotemporal expression profiles. Several recent reports suggest that lncRNAs
      are involved in responses of the central nervous system (CNS) following acute
      injuries. However, their role in sevoflurane anesthesia-mediated cognitive
      dysfunction has not been studied. RNA immunoprecipitation (RIP) combined with qRT
      PCR detection of six different lncRNAs showed that the HOTAIR lncRNAs were
      significantly more bound to both Sin3A and coREST, both corepressors of the RE-1
      silencing transcription factor, within rat hippocampus following sevoflurane
      anesthesia compared with sham. Sevoflurane inhalation resulted in significant
      inhibition of brain-derived neurotrophic factor (BDNF) and cognitive impairment.
      Treatment with a combination of siRNAs targeting HOTAIR rescued BDNF expression
      and improved cognitive responses. Taken together, our results suggest that
      sevoflurane-mediated brain function impairment is at least in part mediated by
      the HOTAIR lncRNA.

PMID- 29352446
TI  - Mycobacterium marinum Infection in Zebrafish and Microglia Imitates the Early
      Stage of Tuberculous Meningitis.
AB  - Mycobacterium tuberculosis (M. tuberculosis) invading and activating microglia
      causes the most serious subtypes of tuberculosis called tubercular meningitis.
      However, the developmental process of tubercular meningitis, especially the early
      phase, is poorly understood due to lacking well-established and well-accepted
      visible models in vitro and in vivo. Here, consistent with one recent report, we
      found Mycobacterium marinum (M. marinum) invade the zebrafish brain and
      subsequently cause granuloma-like structures. We further showed that M. marinum,
      which shares similar characteristics with M. tuberculosis, can invade microglia
      and replicate in microglia, which subsequently promote the secretion of pro
      inflammatory cytokines such as IL-1beta, IL-6, and TNF-alpha. M. marinum
      infection in microglia can also promote autophagy, which conversely limits the
      replication of M. marinum. Thus, pharmacological activation of autophagy by
      rapamycin could prevent M. marinum replication. Our study provides in vivo and in
      vitro models to study underlying pathogenic mechanisms of tubercular meningitis
      by using M. marinum. Our results also showed that activation of autophagy could
      be a meaningful way to prevent tubercular meningitis.

PMID- 29352447
TI  - Long-term endocrine effects and trends in body mass index changes in patients
      with childhood-onset brain tumors.
AB  - As survival rates have improved owing to advances in management strategies for
      pediatric brain tumors, long-term complications such as endocrine dysfunction,
      have emerged as a major issue. This study investigated the long-term endocrine
      effects of childhood-onset brain tumors in a large number of patients. This study
      included 151 patients with brain tumors diagnosed between January 1995 and
      December 2016. The following data were retrospectively reviewed: tumor location,
      tumor histology, endocrine abnormalities, hypothalamic involvement on brain
      imaging, treatment modalities, and trends in body mass index. The mean age at
      diagnosis of patients with sellar/suprasellar (SE/SUP-SE) tumors and
      supra/infratentorial (ST/IT) tumors was 9.9 +/- 4.5 and 6.5 +/- 4.2 years,
      respectively. In patient with prepubertal age at diagnosis, height standard
      deviation score was lower in patients with SE/SUP-SE tumors at diagnosis (P =
      0.031), which was lower in patients with ST/IT tumors at the final visit (P <
      0.001). The prevalence of combined pituitary hormone deficiencies was higher
      among patients with SE/SUP-SE tumors than in those with ST/IT tumors (81.7 vs.
      36.1%, P < 0.001). Among 98 non-obese patients with SE/SUP-SE tumors, 36.7%
      developed obesity. The prevalence of combined pituitary hormone deficiencies and
      obesity was higher in patients with SE/SUP-SE tumors than in those with tumors in
      other locations; growth impairment was more severe in patients with ST/IT tumors.

PMID- 29352448
TI  - Mesenchymal Stem Cell Deformability and Implications for Microvascular
      Sequestration.
AB  - Mesenchymal stem cells (MSCs) have received considerable attention in
      regenerative medicine, particularly in light of prospects for targeted delivery
      by intra-arterial injection. However, little is known about the mechanics of MSC
      sequestration in the microvasculature and the yield pressure (PY), above which
      MSCs will pass through microvessels of a given diameter. The objectives of the
      current study were to delineate the dependency of PY on cell size and the
      heterogeneity of cell mechanical properties and diameters (DCELL) of cultured
      MSCs. To this end the transient filtration test was employed to elucidate the
      mean filtration pressure (<PY>) for an ensemble of pores of a given size (DPORE)
      similar to in vivo microvessels. Cultured MSCs had a log-normal distribution of
      cell diameters (DCELL) with a mean of 15.8 +/- 0.73 SD MUm. MSC clearance from
      track-etched polycarbonate filters was studied for pore diameters of 7.3-15.4
      MUm. The pressure required to clear cells from filters with 30-85 * 103 pores
      rose exponentially with the ratio lambda = DCELL/DPORE for 1.1 <= lambda <= 2.2.
      The clearance of cells from each filter was characterized by a log-normal
      distribution in PY, with a mean filtration pressure of 0.02 <= <PY> <= 6.7 cmH2O.
      For lambda <= 1.56, the yield pressure (PY) was well represented by the cortical
      shell model of a cell with a viscous interior encapsulated by a shell under
      cortical tension tau0 = 0.99 +/- 0.42 SD dyn/cm. For lambda > 1.56, the <PY>
      characteristic of the cell population rose exponentially with lambda. Analysis of
      the mean filtration pressure (<PY>) of each sample suggested that the larger
      diameter cells that skewed the distribution of DCELL contributed to about 20% of
      the mean filtration pressure. Further, if all cells had the same deformability
      (i.e., PY as a function of lambda) as the average cell population, then <PY>
      would have risen an order of magnitude above the average from fivefold at lambda
      = 1.56 to 200-fold at lambda = 2.1. Comparison of <PY> to published microvascular
      pressures suggested that <PY> may exceed microvessel pressure drops for lambda
      exceeding 2.1, and rise 14-fold above capillary pressure drop at lambda = 3
      leading to 100% sequestration. However, due to the large variance of in vivo
      microvascular pressures entrapment of MSCs may be mitigated. Thus it is suggested
      that selecting fractions of the MSC population according to cell deformability
      may permit optimization of entrapment at sites targeted for tissue regeneration.

PMID- 29352449
TI  - Continuous Exposure to Microplastics Does Not Cause Physiological Effects in the
      Cultivated Mussel Perna perna.
AB  - The environmental impact of microplastics is a challenging theme, especially
      under realistic experimental conditions. We investigated physiological responses
      to 0.1-1.0 MUm PVC particles intake by the mussel Perna perna after a relative
      long-term exposure (90 days) at a less extreme concentration compared with
      previous studies (0.125 g/L). Microplastic intake was inferred by the presence of
      PVC in the feces of mussels, and physiological damages were assessed through
      ingestion rate, assimilation efficiency, growth rate, cellular and molecular
      biomarkers (lysosomal integrity, lipid peroxidation, and DNA damage), and
      condition index. All physiological responses showed nonsignificant effects of the
      microplastics on the exposed mussels. We suggest that, despite the experimental
      concentration of microplastics, mussels were able to acclimate to the exposure
      through their abilities for long-term recovery and tolerance to stresses. These
      data have positive implications for environmental health and in terms of human
      food resource because mussel farming is a worldwide practice that heavily relies
      on plastic materials, increasing the chances of microplastic exposure and mussels
      contamination.

PMID- 29352450
TI  - Carrier-mediated uptake of clonidine in cultured human lung cells.
AB  - The lung is a preferential organ site for accumulation of lipophilic basic amine
      drugs, so-called pneumophilic drugs and belonging to various pharmacological
      classes, which can result in lung toxicity. In order to investigate the mechanism
      involved in such pulmonary accumulation of drugs, uptake of clonidine, used here
      as a prototypical basic amine drug, was characterized in cultured human lung
      cells. Clonidine accumulation in lung alveolar A549 cells was found to be
      temperature- and pH-dependent; it was saturable, with a Michaelis-Menten affinity
      constant (Km) value of 569.4 MUM. Various pneumophilic drugs, including
      amitriptyline, verapamil, propranolol, chlorpromazine, imipramine, and quinidine,
      markedly cis-inhibited clonidine uptake in A549 cells, in a dose-dependent manner
      for at least some of them. They additionally trans-stimulated clonidine efflux
      from A549 cells, thus suggesting that they are substrates for the putative
      clonidine transporter. In addition to alveolar A549 cells, bronchial epithelial
      BEAS-2B cells as well as lung endothelial HULEC-5a cells were found to exhibit
      clonidine accumulation abrogated by amitriptyline, verapamil, and chlorpromazine.
      Taken together, these data likely provided evidence for carrier-mediated uptake
      of clonidine in human lung cells. This carrier, which remains to be molecularly
      identified, interacts with various pneumophilic drugs, suggesting that it may
      contribute to lung accumulation of these drugs in a notable way.

PMID- 29352451
TI  - Involvement of Tsukushi in diverse developmental processes.
AB  - Tsukushi (TSK) is a small signaling molecule which takes part in different
      developmental processes of multiple vertebrate organisms. The diverse activity of
      TSK depends on its ability to bind various intermediate molecules from different
      major signaling pathways. Interactions of TSK with BMP, FGF, TGF-beta and Wnt
      pathways have already been confirmed. In this review, we will introduce the
      latest information regarding the involvement of TSK in developmental events. We
      suggest a fine tuning role for TSK in multiple signaling cascades. Also, we
      recommend further studies on the developmental role of TSK to fully reveal its
      potential.

PMID- 29352452
TI  - The determinants of reduced dietary intake in hospitalised colorectal cancer
      patients.
AB  - PURPOSE: Patients with colorectal cancer (CRC) often experience malnutrition and
      weight loss, largely resulting from reduced dietary intake. The aim of this study
      was to identify determinants of reduced dietary intake in order to facilitate
      early recognition of malnutrition and optimise nutritional treatment. METHODS:
      Data from nutritionDay, an international 1-day survey investigating patient,
      disease and food profiles, were used. To identify determinants of dietary intake,
      defined as normal vs. reduced in the last week, univariate and multivariate
      logistic regressions were performed. RESULTS: Of 1131 hospitalised CRC patients,
      54% reported reduced dietary intake. Patient- and disease-related characteristics
      significantly associated with reduced dietary intake were female gender (odds
      ratio (OR) 1.38), cancer stage III (OR 1.52) or IV (OR 1.70) vs. I, performance
      status 2 (OR 1.56), 3 (OR 2.37) or 4 (OR 4.15) vs. 0, duration since hospital
      admission of >= 4 days (OR 4-7 days, 1.91; 8-21 days, 1.97; > 21 days, 1.92) vs.
      < 4 days, and unintentional weight loss (OR 2.56). Additionally, higher symptom
      scores of pain, weakness, depression, tiredness and lack of appetite were
      associated with reduced intake. CONCLUSIONS: Patient- and disease-related
      determinants for reduced dietary intake were being female, higher cancer stage,
      worse performance status, duration since hospital admission >= 4 days and
      unintentional weight loss. Furthermore, multiple symptoms were associated with a
      reduced dietary intake. Future trials should assess whether early recognition of
      patients at risk of malnutrition and the combination of treating symptoms and
      dietary advice result in improved intake and treatment-related outcomes.

PMID- 29352453
TI  - Measuring surgical safety during minimally invasive surgical procedures: a
      validation study.
AB  - BACKGROUND: During the implementation of new interventions (i.e., surgical
      devices and technologies) in the operating room, surgical safety might be
      compromised. Current safety measures are insufficient in detecting safety hazards
      during this process. The aim of the study was to observe whether surgical teams
      are capable of measuring surgical safety, especially with regard to the
      introduction of new interventions. METHODS: A Surgical Safety Questionnaire was
      developed that had to be filled out directly postoperative by three surgical team
      members. A potential safety concern was defined as at least one answer between
      (strongly) disagree and indifferent. The validity of the questionnaire was
      assessed by comparison with the results from video analysis. Two different
      observers annotated the presence and effect of surgical flow disturbances during
      40 laparoscopic hysterectomies performed between November 2010 and April 2012.
      RESULTS: The surgeon reported a potential safety concern in 16% (85/520
      questions). With respect to the scrub nurse and anesthesiologist, this was both
      9% (46/520). With respect to the preparation, functioning, and ease of use of the
      devices in 37.5-47.5% (15-19/40 procedures) a potential safety concern was
      reported by one or more team members. During procedures after which a potential
      safety concern was reported, surgical flow disturbances lasted a higher
      percentage of the procedure duration [9.3 +/- 6.2 vs. 2.9 +/- 3.7% (mean +/- SD),
      p < .001]. After procedures during which a new instrument or device was used,
      more potential safety concerns were reported (51.2 vs. 23.1%, p < .001).
      CONCLUSIONS: Potential safety concerns were especially reported during procedures
      in which a relatively high percentage of the duration consisted of surgical flow
      disturbances and during procedures in which a new instrument or device was used.
      The Surgical Safety Questionnaire can act as a validated tool to evaluate and
      maintain surgical safety during minimally invasive procedures, especially during
      the introduction of a new intervention.

PMID- 29352454
TI  - Decreased opioid consumption and enhance recovery with the addition of IV
      Acetaminophen in colorectal patients: a prospective, multi-institutional,
      randomized, double-blinded, placebo-controlled study (DOCIVA study).
AB  - BACKGROUND: We hypothesized that administration of IV acetaminophen alone would
      reduce the opioid consumption in post-operative colorectal surgery and reduce the
      side effects of narcotics. METHODS: Patients were randomized to receive either IV
      acetaminophen or placebo in addition to opioid PCA. Primary endpoints evaluated
      were opioid consumption and pain visual analogue scale score (PVASS) during first
      48 h post-operatively. Secondary endpoints evaluated were time of return of GI
      function (ROGIF), time to diet ordered (TTDO), length of hospital stay (LOHS),
      and occurrence of ileus. RESULTS: 105 patients were enrolled and 97 remained in
      the study after exclusion (control group n = 50; study group n = 47). Mean +/-
      SEs of opioid consumption in the study group was 21.5 +/- 1.8 mg of morphine
      equivalent (ME) and 35.0 +/- 3.3 mg ME at 24 and 48 h, respectively, versus 36.4
      +/- 4.1 mg ME and 59.7 +/- 6.7 mg ME in the control group (p = 0.002 and 0.002).
      PVASS levels were lower in the study group at all intervals at 3, 8, 24, and 48 h
      (p = 0.02, 0.006, < 0.01, and 0.02). ROGIF, TTDO, and LOHS were also found to be
      lower in the study group (p <= 0.01, < 0.01, and 0.002). The rate of ileus was
      reduced by using IV acetaminophen (22% vs 2.1%; p = 0.004). CONCLUSIONS: IV
      acetaminophen helps to reduce opioid consumption for patients undergoing
      colorectal surgery. Additionally, there appears to be a shortened length of
      hospital stay, better pain control, reduced time to return of bowel function, and
      lower rate of post-operative ileus in patients receiving IV acetaminophen.

PMID- 29352455
TI  - Clinical features in a series of 258 Japanese pediatric patients with thrombotic
      microangiopathy.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) includes hemolytic uremic syndrome
      (HUS) and thrombotic thrombocytopenic purpura (TTP). This study examined the
      epidemiological characteristics of pediatric patients with TMA classified
      according to etiology. METHODS: The survey evaluated 258 Japanese pediatric
      patients diagnosed with TMA between 2012 and 2015. RESULTS: The primary diseases
      responsible for TMA were categorized as TTP (15 cases), Shiga toxin-producing
      Escherichia coli-associated HUS (STEC-HUS) (166 cases), atypical HUS (aHUS) (40
      cases), and secondary TMA (27 cases). The remaining 10 cases were unable to be
      classified to one of the four categories of the primary disease. Renal
      replacement therapy was required in the acute phase in 103 patients with TMA,
      including 65 with STEC-HUS, 22 with aHUS, two with TTP, 10 with secondary TMA,
      and four unclassified cases. The last observational findings were normal renal
      function in 95 patients and chronic kidney disease (CKD) stage 1 in 62. For 31
      patients, chronic renal insufficiency (CKD stage 2-5) persisted, including four
      patients with end-stage kidney disease (CKD stage 5). Seventeen patients suffered
      recurrence of TMA, and eight patients died. CONCLUSION: This study clarified
      differences in the relative proportions of primary diseases between patients from
      Japan and North America and Europe. The difference may be attributable to the
      lower estimated incidence of STEC-HUS in Japan.

PMID- 29352456
TI  - Recombinant growth hormone treatment, osteoporosis and fractures, more
      complicated than it seems!

PMID- 29352457
TI  - Geographic vocal variation and perceptual discrimination abilities in male
      Australian sea lions.
AB  - Vocal characteristics can vary among and within populations. In species with
      geographic variation in the structure of vocalizations, individuals may have the
      ability to discriminate between calls from local and non-local individuals. The
      ability to distinguish differences in acoustic signals is likely to have a
      significant influence on the outcome of social interactions between individuals,
      including potentially mate selection and breeding success. Pinnipeds (seals, fur
      seals, sea lions and walruses) are highly vocal yet the Australian sea lion
      (Neophoca cinerea) is the only eared seal known to show geographic vocal
      variation in male barks. Barks are produced in many social interactions and
      encode sufficient information for both individual and colony identity to be
      discriminable. Yet until now, whether males could themselves discriminate these
      bark differences was unclear. We performed playback experiments in four breeding
      colonies to investigate whether males can discriminate local from non-local
      barks. Overall, males responded more strongly to barks from their own colony
      compared to barks from other colonies regardless of whether those other colonies
      were close or distant. Competition for females is high in Australian sea lions,
      but mating periods are asynchronous across colonies. The ability to correctly
      assess whether a male is from the same colony, thus representing a potential
      competitor for mates, or merely a visitor from elsewhere, may influence how males
      interact with others. Given the high cost of fighting, the ability to discern
      competitors may influence the nature of male-male interactions and ultimately
      influence how they allocate reproductive effort.

PMID- 29352458
TI  - Polyhydroxybutyrate (PHB) Synthesis by Spirulina sp. LEB 18 Using Biopolymer
      Extraction Waste.
AB  - The reuse of waste as well as the production of biodegradable compounds has for
      years been the object of studies and of global interest as a way to reduce the
      environmental impact generated by unsustainable exploratory processes. The
      conversion of linear processes into cyclical processes has environmental and
      economic advantages, reducing waste deposition and reducing costs. The objective
      of this work was to use biopolymer extraction waste in the cultivation of
      Spirulina sp. LEB 18, for the cyclic process of polyhydroxybutyrate (PHB)
      synthesis. Concentrations of 10, 15, 20, 25, and 30% (v/v) of biopolymer
      extraction waste were tested. For comparison, two assays were used without
      addition of waste, Zarrouk (SZ) and modified Zarrouk (ZM), with reduction of
      nitrogen. The assays were carried out in triplicate and evaluated for the
      production of microalgal biomass and PHB. The tests with addition of waste
      presented a biomass production statistically equal to ZM (0.79 g L-1) (p < 0.1).
      The production of PHB in the assay containing 25% of waste was higher when
      compared to the other cultivations, obtaining 10.6% (w/w) of biopolymer. From the
      results obtained, it is affirmed that the use of PHB extraction waste in the
      microalgal cultivation, aiming at the synthesis of biopolymers, can occur in a
      cyclic process, reducing process costs and the deposition of waste, thus favoring
      the preservation of the environment.

PMID- 29352459
TI  - Web-Based Training Methods for Behavioral Health Providers: A Systematic Review.
AB  - There has been an increase in the use of web-based training methods to train
      behavioral health providers in evidence-based practices. This systematic review
      focuses solely on the efficacy of web-based training methods for training
      behavioral health providers. A literature search yielded 45 articles meeting
      inclusion criteria. Results indicated that the serial instruction training method
      was the most commonly studied web-based training method. While the current review
      has several notable limitations, findings indicate that participating in a web
      based training may result in greater post-training knowledge and skill, in
      comparison to baseline scores. Implications and recommendations for future
      research on web-based training methods are discussed.

PMID- 29352460
TI  - Pelvic floor muscle function and quality of life in postmenopausal women with and
      without pelvic floor dysfunction.
AB  - INTRODUCTION: This study aims to compare pelvic floor muscle (PFM) function in
      postmenopausal women with and without pelvic floor dysfunction (PFD) and the
      relation between PFM function and quality of life. MATERIAL AND METHODS: A case
      control study with 216 postmenopausal women with (n = 126) and without (n = 90)
      PFD. PFM function was assessed by digital vaginal palpation using the PERFECT
      scale. Specific quality of life was evaluated using the King's Health
      Questionnaire for women with urinary incontinence and the Prolapse Quality-of
      Life Questionnaire for women with pelvic organ prolapse. We analyzed women with
      PFD into two categories: Oxford's grade <=2 or >=3 using a chi-squared test.
      RESULTS: Out of 126 womem with PFD 44 (34.9%) presented stress urinary
      incontinence, 21 (16.6%) had pelvic organ prolapse and 61 (48.4%) had urinary
      incontinence + pelvic organ prolapse. Strength had a median value 2 (0-5) in all
      women studied and most of them had insufficient strength, reduced endurance and
      repetition without statistical difference between groups. Incontinent women with
      strength <=2 had worse perception of general health domain of King's Health
      Questionnaire (p = 0.007). No association was found between PFM function and
      Prolapse Quality-of-Life Questionnaire. CONCLUSIONS: PFM function assessed by
      bidigital palpation in postmenopausal women was not sufficiently sensitive to
      differentiate between women with vs. women without PFM dysfunction and was not
      related with specific quality of life in women with urinary incontinence and
      pelvic organ prolapse, respectively. These data should be used to reinforce the
      widespread recommendation that PFM training is essencial in PFD treatment.

PMID- 29352461
TI  - Clinical and microbiological evaluation of the effect of Lactobacillus reuteri in
      the treatment of mucositis and peri-implantitis: A triple-blind randomized
      clinical trial.
AB  - BACKGROUND AND OBJECTIVE: Oral probiotics appear to improve the treatment of
      periodontal diseases but there is limited evidence on their efficacy in the
      treatment of peri-implant diseases. The objective of the present study was to
      evaluate, clinically and microbiologically, the effect of the oral probiotic,
      Lactobacillus reuteri Prodentis, as adjuvant to non-surgical mechanical therapy
      in implants with mucositis or peri-implantitis, placed in patients with a history
      of periodontal disease. MATERIAL AND METHODS: A randomized, controlled, parallel
      design, triple-blind prospective clinical study was designed. Patients included
      in the study were partially edentulous and had implants with mucositis or peri
      implantitis. Implants with radiographic bone loss of >=5 mm and/or >=50% of the
      implant length were excluded, and only one implant per patient was included.
      After non-surgical mechanical therapy, subjects were randomly assigned to take
      either 1 probiotic lozenge or 1 placebo lozenge every day for 30 days. Clinical
      measurements were taken in the whole mouth (general plaque index and general
      bleeding on probing) and at the implant site (probing pocket depth, plaque index
      and bleeding on probing) at baseline and 30 and 90 days Microbiological
      examination (to identify Aggregatibacter actinomycetemcomitans, Tannerella
      forsythia, Porphyromonas gingivalis, Treponema denticola, Prevotella intermedia,
      Peptostreptococcus micros, Fusobacterium nucleatum, Campylobacter rectus and
      Eikenella corrodens) was performed at the same study time points that clinical
      measurements were made. RESULTS: A total of 44 patients - 22 with mucositis and
      22 with peri-implantitis - randomly received treatment with either probiotic or
      placebo. The probiotic L. reuteri, together with mechanical therapy, produced an
      additional improvement over treatment with mechanical therapy alone, both in the
      general clinical parameters of patients with mucositis (bleeding on probing) and
      at the level of implants with mucositis (probing pocket depth) or peri
      implantitis (bleeding on probing and probing pocket depth). However, L. reuteri
      had a very limited effect on the peri-implant microbiota because the only
      parameter in which a significant decrease was found was the bacterial load of P.
      gingivalis in implants with mucositis (P = .031). CONCLUSION: The administration
      of a daily lozenge of L. reuteri for 30 days, together with mechanical
      debridement of the whole mouth, improved the clinical parameters of implants with
      mucositis or peri-implantitis over a period of at least 90 days, but the
      microbiological effect was much more limited. Probiotics provide an alternative
      therapeutic approach to consider in the prevention and treatment of peri-implant
      diseases, but further long-term prospective studies with standardized variables
      are needed.

PMID- 29352463
TI  - Temperature dependency of intraguild predation between native and invasive crabs.
AB  - Environmental factors such as temperature can affect the geographical
      distribution of species directly by exceeding physiological tolerances, or
      indirectly by altering physiological rates that dictate the sign and strength of
      species interactions. Although the direct effects of environmental conditions are
      relatively well studied, the effects of environmentally mediated species
      interactions have garnered less attention. In this study, we examined the
      temperature dependency of size-structured intraguild predation (IGP) between
      native blue crabs (Callinectes sapidus, the IG predator) and invasive green crabs
      (Carcinus maenas, the IG prey) to evaluate how the effect of temperature on
      competitive and predatory rates may influence the latitudinal distribution of
      these species. In outdoor mesocosm experiments, we quantified interactions
      between blue crabs, green crabs, and shared prey (mussels) at three temperatures
      reflective of those across their range, using two size classes of blue crab. At
      low temperatures, green crabs had a competitive advantage and IGP by blue crabs
      on green crabs was low. At high temperatures, size-matched blue and green crabs
      were competitively similar, large blue crabs had a competitive advantage, and IGP
      on green crabs was high. We then used parameter values generated from these
      experiments (temperature- and size-dependent attack rates and handling times) in
      a size-structured IGP model in which we varied IGP attack rate, maturation rate
      of the blue crab from the non-predatory to predatory size class, and resource
      carrying capacity at each of the three temperatures. In the model, green crabs
      were likely to competitively exclude blue crabs at low temperature, whereas blue
      crabs were likely to competitively and consumptively exclude green crabs at
      higher temperatures, particularly when resource productivities and rates of IGP
      were high. While many factors may play a role in delimiting species ranges, our
      results suggest that temperature-dependent interactions can influence local
      coexistence and are worth considering when developing mechanistic species
      distribution models and evaluating responses to environmental change.

PMID- 29352462
TI  - Effect of methyl salicylate in combination with 1-methylcyclopropene on
      postharvest quality and decay caused by Botrytis cinerea in tomato fruit.
AB  - BACKGROUND: Postharvest diseases result in major losses in fruits. Tomato is
      susceptible to postharvest rot caused by Botrytis cinerea and is regarded as a
      good model system to study postharvest disease and quality deterioration in
      fruit. To develop a safe and effective technique to alleviate disease and
      maintain fruit quality, the effects of methyl salicylate (MeSA) and 1
      methylcyclopropene (1-MCP) either separately or combined on quality and gray mold
      caused by B. cinerea in tomato fruit were investigated. RESULTS: The results
      showed that application of MeSA (0.05 mmol L-1 ) delayed fruit ripening and
      reduced gray mold. Compared with MeSA treatment, 1-MCP (0.5 uL L-1 ) effectively
      delayed fruit ripening. Further, MeSA combined with 1-MCP treatment was more
      effective in inhibiting fungal decay during storage than MeSA treatment alone.
      The combined treatment not only enhanced pathogenesis-related protein 1 (PR1)
      expression, activities of defense enzymes and total phenolic content but also
      inhibited the increase in electrical conductivity and malondialdehyde content.
      The combined treatment was also more effective in retaining firmness, color
      change and titratable acidity content than MeSA treatment alone. CONCLUSION: MeSA
      combined with 1-MCP treatment was a useful technique to maintain quality and
      alleviate gray mold in postharvest tomato fruit during storage. (c) 2018 Society
      of Chemical Industry.

PMID- 29352465
TI  - Efficacy of local phytotherapy in the nonsurgical treatment of periodontal
      disease: A systematic review.
AB  - Herbal drugs are commonly used in the treatment of several diseases, including
      periodontitis. So far, no systematic review had evaluated the evidence regarding
      the efficacy of these agents in the treatment of periodontal disease. Therefore,
      the purpose of this review was to evaluate the effect of local application of
      phytotherapic agents as adjuncts to scaling and root planing (SRP), compared to
      SRP alone, on clinical parameters of chronic periodontal patients. Only
      randomized controlled trials of at least 3 months follow-up, of SRP alone in
      association with local phytotherapic agents were included. MEDLINE (PubMed),
      Google Scholar and LILACS databases were searched for articles published up to
      October 2016. Random-effects meta-analyses were conducted for clinical attachment
      level and probing pocket depth (PPD) change after treatment. Of 1861 papers
      potentially relevant, 7 were included. All studies showed that periodontal
      treatment in association with local phytotherapic delivery promotes a significant
      PPD reduction and the majority of them showed clinical attachment level gain. The
      local use of phytotherapy as an adjunct to SRP may promote additional benefits in
      PPD reduction and clinical attachment level gain. However, these results must be
      interpreted with caution due to the small sample size, high risk of bias and
      heterogeneity of the studies.

PMID- 29352464
TI  - Origin of heterogeneous spiking patterns from continuously distributed ion
      channel densities: a computational study in spinal dorsal horn neurons.
AB  - KEY POINTS: Distinct spiking patterns may arise from qualitative differences in
      ion channel expression (i.e. when different neurons express distinct ion
      channels) and/or when quantitative differences in expression levels qualitatively
      alter the spike generation process. We hypothesized that spiking patterns in
      neurons of the superficial dorsal horn (SDH) of spinal cord reflect both
      mechanisms. We reproduced SDH neuron spiking patterns by varying densities of KV
      1- and A-type potassium conductances. Plotting the spiking patterns that emerge
      from different density combinations revealed spiking-pattern regions separated by
      boundaries (bifurcations). This map suggests that certain spiking pattern
      combinations occur when the distribution of potassium channel densities straddle
      boundaries, whereas other spiking patterns reflect distinct patterns of ion
      channel expression. The former mechanism may explain why certain spiking patterns
      co-occur in genetically identified neuron types. We also present algorithms to
      predict spiking pattern proportions from ion channel density distributions, and
      vice versa. ABSTRACT: Neurons are often classified by spiking pattern. Yet, some
      neurons exhibit distinct patterns under subtly different test conditions, which
      suggests that they operate near an abrupt transition, or bifurcation. A set of
      such neurons may exhibit heterogeneous spiking patterns not because of
      qualitative differences in which ion channels they express, but rather because
      quantitative differences in expression levels cause neurons to operate on
      opposite sides of a bifurcation. Neurons in the spinal dorsal horn, for example,
      respond to somatic current injection with patterns that include tonic, single,
      gap, delayed and reluctant spiking. It is unclear whether these patterns reflect
      five cell populations (defined by distinct ion channel expression patterns),
      heterogeneity within a single population, or some combination thereof. We
      reproduced all five spiking patterns in a computational model by varying the
      densities of a low-threshold (KV 1-type) potassium conductance and an
      inactivating (A-type) potassium conductance and found that single, gap, delayed
      and reluctant spiking arise when the joint probability distribution of those
      channel densities spans two intersecting bifurcations that divide the parameter
      space into quadrants, each associated with a different spiking pattern. Tonic
      spiking likely arises from a separate distribution of potassium channel
      densities. These results argue in favour of two cell populations, one
      characterized by tonic spiking and the other by heterogeneous spiking patterns.
      We present algorithms to predict spiking pattern proportions based on ion channel
      density distributions and, conversely, to estimate ion channel density
      distributions based on spiking pattern proportions. The implications for
      classifying cells based on spiking pattern are discussed.

PMID- 29352466
TI  - Experimental evidence that density dependence strongly influences plant invasions
      through fragmented landscapes.
AB  - Populations of range expanding species encounter patches of both favorable and
      unfavorable habitat as they spread across landscapes. Theory shows that
      increasing patchiness slows the spread of populations modeled with continuously
      varying population density when dispersal is not influence by the environment or
      individual behavior. However, as is found in uniformly favorable landscapes,
      spread remains driven by fecundity and dispersal from low density individuals at
      the invasion front. In contrast, when modeled populations are composed of
      discrete individuals, patchiness causes populations to build up to high density
      before dispersing past unsuitable habitat, introducing an important influence of
      density dependence on spread velocity. To test the hypothesized interaction
      between habitat patchiness and density dependence, we simultaneously manipulated
      these factors in a greenhouse system of annual plants spreading through
      replicated experimental landscapes. We found that increasing the size of gaps and
      amplifying the strength of density dependence both slowed spread velocity, but
      contrary to predictions, the effect of amplified density dependence was similar
      across all landscape types. Our results demonstrate that the discrete nature of
      individuals in spreading populations has a strong influence on how both landscape
      patchiness and density dependence influence spread through demographic and
      dispersal stochasticity. Both finiteness and landscape structure should be
      critical components to theoretical predictions of future spread for range
      expanding native species or invasive species colonizing new habitat.

PMID- 29352467
TI  - Systematic misclassification of gestational age by ultrasound biometry:
      implications for clinical practice and research methodology in the Nordic
      countries.
AB  - Historically, pregnancy dating has been based on self-reported information on the
      first day of the last menstrual period. In the 1970s, ultrasound biometry was
      introduced as an alternative for pregnancy dating and is now the leading method
      in Nordic countries. The use of ultrasound led to a reduction of post-term births
      and fewer inductions, and is considered more precise than last menstrual period
      based methods for pregnancy dating. Nevertheless, differences in early growth and
      specific situations, such as maternal obesity, can render its estimates less
      precise, leading to gestational age misclassification. Clinical implications of
      ultrasound dating include effect on timely induction in case of post-term
      pregnancies, treatment with corticosteroids in cases of anticipated preterm
      delivery and decision on viability in cases of extreme prematurity. Furthermore,
      gestational age misclassification may influence the numbers and the magnitude of
      some adverse perinatal outcomes, closely related to gestational age, which are
      recorded in the Nordic birth registers.

PMID- 29352468
TI  - Developmental plasticity of GABAergic neurotransmission to brainstem motoneurons.
AB  - KEY POINTS: Critical homeostatic behaviours such as suckling, swallowing and
      breathing depend on the precise control of tongue muscle activity. Perinatal
      nicotine exposure has multiple effects on baseline inhibitory GABAergic
      neurotransmission to hypoglossal motoneurons (XIIMNs), consistent with
      homeostatic compensations directed at maintaining normal motoneuron output.
      Developmental nicotine exposure (DNE) alters how GABAergic neurotransmission is
      modulated by acute activation of nicotinic acetylcholine receptors, which may
      provide insight into mechanisms by which nicotine exposure alters motor function
      under conditions that result in increased release of GABA, such as hypoxia, or
      endogenous acetylcholine, as occurs in the transition from NREM to REM sleep, or
      in response to exogenous nicotine. ABSTRACT: Nicotinic acetylcholine receptor
      (nAChR) signalling regulates neuronal differentiation and synaptogenesis. Here we
      test the hypothesis that developmental nicotine exposure (DNE) disrupts the
      development of GABAergic synaptic transmission to hypoglossal motoneurons
      (XIIMNs). GABAergic spontaneous and miniature inhibitory postsynaptic currents
      (sIPSCs/mIPSCs) were recorded from XIIMNs in brainstem slices from control and
      DNE rat pups of either sex, 1-5 days old, at baseline and following acute
      stimulation of nAChRs with nicotine. At baseline, sIPSCs were less frequent and
      smaller in DNE cells (consistent with decreased action potential-mediated GABA
      release), and mIPSCs were more frequent (consistent with increased vesicular GABA
      release from presynaptic terminals). Acute nicotine challenge increased sIPSC
      frequency in both groups, though the increase was greater in DNE cells. Acute
      nicotine challenge did not change the frequency of mIPSCs in either group, though
      mIPSC amplitude increased significantly in DNE cells, but not control cells.
      Stimulation of postsynaptic GABAA receptors with muscimol caused a significantly
      greater chloride current in DNE cells than in control cells. The increased
      quantal release of GABA, coupled with the rise in the strength of postsynaptic
      inhibition may be homeostatic adjustments to the decreased action-potential
      mediated input from GABAergic interneurons. However, this will exaggerate
      synaptic inhibition under conditions where the release of GABA (e.g. hypoxia) or
      ACh (sleep-wake transitions) is increased. These findings reveal a mechanism that
      may explain why DNE is associated with deficits in the ability to respond
      appropriately to chemosensory stimuli or to changes in neuromodulation secondary
      to changes in central nervous system state.

PMID- 29352469
TI  - Amoxicillin-current use in swine medicine.
AB  - Amoxicillin has become a major antimicrobial substance in pig medicine for the
      treatment and control of severe, systemic infections such as Streptococcus suis.
      The minimum inhibitory concentration 90% (MIC 90) is 0.06 MUg amoxicillin/ml, and
      the proposed epidemiological cut-off value (ECOFF) is 0.5 MUg/ml, giving only
      0.7% of isolates above the ECOFF or of reduced susceptibility. Clinical
      breakpoints have not been set for amoxicillin against porcine pathogens yet,
      hence the use of ECOFFs. It has also been successfully used for bacterial
      respiratory infections caused by Actinobacillus pleuropneumoniae and Pasteurella
      multocida. The ECOFF for amoxicillin against A. pleuropneumoniae is also 0.5
      MUg/ml demonstrating only a reduced susceptibility in 11.3% of isolates.
      Similarly, P. multocida had an ECOFF of 1.0 MUg/ml and a reduced susceptibility
      in only 2.6% of isolates. This reduced susceptibility disappears when combined
      with the beta-lactamase inhibitor, clavulanic acid, demonstrating that it is
      primarily associated with beta-lactamase production. In contrast, amoxicillin is
      active against Escherichia coli and Salmonella species but using ECOFFs of 8.0
      and 4.0 MUg/ml, respectively, reduced susceptibility can be seen in 70.9% and
      67.7% of isolates. These high levels of reduced susceptibility are primarily due
      to beta-lactamase production also, and most of this resistance can be overcome by
      the combination of amoxicillin with clavulanic acid. Currently, amoxicillin alone
      is considered an extremely valuable antimicrobial in both human and animal
      medicine and remains in the critically important category of antibiotics
      alongside the fluoroquinolones and macrolides by the World Health Organization as
      well as the third- and fourth-generation cephalosporins, but these cephalosporins
      show marked resistance to basic beta-lactamase production and are only destroyed
      by the extended-spectrum beta-lactamases. Amoxicillin alone and in combination
      with clavulanic acid are currently classed together in Category 2 in the European
      Union. By reviewing the pharmacodynamic data and comparing this with
      pharmacokinetic data from healthy and infected animals and clinical trial data,
      it can be seen that the product has a good efficacy against S. suis and A.
      pleuropneumoniae, in spite of usage over many years. However, it may be much less
      efficacious on its own against E. coli, due to reduced susceptibility and
      resistance associated with beta-lactamase production, which is largely overcome
      by the use of clavulanic acid. It is felt that this differentiation may be useful
      in future classification of amoxicillin alone, in comparison with its combined
      use with clavulanic acid and thereby preserve the use of the more critically
      important antibiotics in veterinary medicine and reducing the risk of their
      resistance being transmitted to human.

PMID- 29352470
TI  - A laser optical method for predicting adulteration of clover honey.
AB  - BACKGROUND: The authenticity of honey is of great importance for commercial and
      health reasons, because adulteration of bee honey with cheaper sweetening
      materials is sometimes carried out for financial gain. The objectives of this
      study were to evaluate clover honey quality according to physicochemical
      characteristics, to measure light transmission through honey samples using a
      visible laser technique (He-Ne laser at 632.8 nm) and to predict types of
      adulterants of clover honey according to the transmission intensity of the laser
      beam through the sample. RESULTS: The transmission intensity of pure clover honey
      was 3520 lx. Addition of water or sugar solution at various concentrations led to
      increased transmission intensities in the range 4720-6980 lx, while addition of
      glucose honey led to increased transmission intensities in the range 3570-4120
      lx. However, addition of starch suspension or black honey led to decreased
      transmission intensities in the ranges 3440-120 and 2770-85 lx respectively. The
      physicochemical properties of pure clover honey were within the standard limits.
      The light microscope image of pollen in the honey indicated that the pollen came
      from the clover plant. CONCLUSION: The transmission intensity method using
      visible laser light to predict the type of adulteration of clover honey can be
      considered a fast and accurate method. (c) 2018 Society of Chemical Industry.

PMID- 29352471
TI  - How do passion for video games and needs frustration explain time spent gaming?
AB  - Research applying self-determination theory and the dualistic model of passion
      (DMP) has shown video games may satisfy basic psychological needs (i.e.,
      competence, autonomy, and relatedness) and be identified as a passion. The DMP
      distinguishes between healthy or harmonious passion and problematic or obsessive
      passion (OP), with the latter reflecting an overreliance towards one's passion to
      obtain needs satisfaction. The experience of daily obstructions to needs
      satisfaction, or needs frustration (NF), may facilitate such an overreliance.
      This study explored how NF and both types of passion explain the amount of time
      that university students spend gaming. The overall association between NF and
      time spent gaming was not significant. However, for video game users with low
      levels of OP for gaming, there was a significant negative association between NF
      and time spent gaming. Additionally, evidence of a mutually reinforcing
      association between NF and OP for gaming indicates that a vicious cycle exists,
      whereby a strong OP for gaming predicts and is reinforced by greater NF. The
      theoretical implications are discussed.

PMID- 29352472
TI  - The bioequivalence of a single intravenous administration of the anesthetic
      alfaxalone in cyclodextrin versus alfaxalone in cyclodextrin plus preservatives
      in cats.
AB  - To demonstrate the bioequivalence of alfaxalone in cyclodextrin (Reference
      Product) to a formulation of alfaxalone in cyclodextrin also containing the
      preservatives ethanol, chlorocresol, and benzethonium chloride (Test Product)
      when administered for the purpose of inducing anesthesia in the cat. Blinded,
      single-dose, randomized, two-period, two-sequence, cross-over bioequivalence
      study with a 7-day washout period between treatments. Twenty-four (12 neutered
      males and 12 intact females), healthy, adult cats weighing 4.1+/-0.9 kg. Cats
      were administered 5 mg/kg IV of alfaxalone in the Reference or Test Product using
      a randomized cross-over design. One-milliliter venous blood samples were
      collected at predetermined time points to 12 hr after drug administration to
      determine alfaxalone plasma concentration over time. Alfaxalone concentrations
      were determined by a validated analytical testing method using HPLC-MS/MS. Plasma
      profiles of alfaxalone concentration against time were analyzed by
      noncompartmental analysis. The pivotal variables for bioequivalence were AUClast
      and Cmax . Equivalence was achieved if the 90% confidence interval for AUClast
      and Cmax fell into the asymmetric +/-20% interval (0.80-1.25). Physiological
      variables, quality of anesthesia visual analog scale (VAS) scoring and anesthetic
      event times were recorded. ANOVA or ANCOVA (single time point), RMANOVA or
      RMANCOVA (multiple time point) was used for normally distributed data. GLIMMIX
      was used for nonnormally distributed data. VAS scores were analyzed as for blood
      bioequivalence data. Variables were evaluated for safety and assessed at alpha =
      0.10. Cmax and AUClast for Reference and Test Products were statistically
      bioequivalent. No physiological variables except for a drug by time interaction
      for respiratory rate differed between treatment groups, and this difference was
      not clinically relevant. No anesthetic event times or VAS scores for quality of
      anesthesia were different between treatment groups. Neither formulation caused
      pain upon injection. The Reference and Test Products are pharmaceutically
      bioequivalent formulations when administered as a single intravenous
      administration for the purpose of induction of anesthesia in cats.

PMID- 29352473
TI  - The impact of MK-467 on plasma drug concentrations, sedation and cardiopulmonary
      changes in sheep treated with intramuscular medetomidine and atipamezole for
      reversal.
AB  - The effect of MK-467, a peripheral alpha2 -adrenoceptor antagonist, on plasma
      drug concentrations, sedation and cardiopulmonary changes induced by
      intramuscular (IM) medetomidine was investigated in eight sheep. Additionally,
      the interactions with atipamezole (ATI) used for reversal were also evaluated.
      Each animal was treated four times in a randomized prospective crossover design
      with 2-week washout periods. Medetomidine (MED) 30 MUg/kg alone or combined in
      the same syringe with MK-467 300 MUg/kg (MMK) was injected intramuscular,
      followed by ATI 150 MUg/kg (MED + ATI and MMK + ATI) or saline intramuscular 30
      min later. Plasma was analysed for drug concentrations, and sedation was
      subjectively assessed with a visual analogue scale. Systemic haemodynamics and
      blood gases were measured before treatments and at intervals thereafter. With MK
      467, medetomidine plasma concentrations were threefold higher prior to ATI, which
      was associated with more profound sedation and shorter onset. No significant
      differences were observed in early cardiopulmonary changes between treatments.
      Atipamezole reversed the medetomidine-related cardiopulmonary changes after both
      treatments. Sedation scores decreased more rapidly when MK-467 was included. In
      this study, MK-467 appeared to have a pronounced effect on the plasma
      concentration and central effects of medetomidine, with minor cardiopulmonary
      improvement.

PMID- 29352474
TI  - Pharmacokinetics of single-dose sildenafil administered orally in clinically
      healthy dogs: Effect of feeding and dose proportionality.
AB  - Basic information related to the pharmacokinetics of sildenafil in dogs is
      scarce. This study aimed to describe the pharmacokinetic properties of oral
      sildenafil and determine the effect of feeding and dose proportionality. The
      effect of feeding on pharmacokinetics of sildenafil (1 mg/kg) was investigated
      using a crossover study with six dogs. In addition, the dose proportionality of
      sildenafil ranging 1-4 mg/kg was evaluated using five dogs in the fasted states.
      The plasma concentrations of sildenafil were determined using high-performance
      liquid chromatography, and pharmacokinetic parameters were calculated using a
      noncompartmental analysis. Sildenafil administrations were well tolerated in all
      studies. Feeding reduced the area under the curve extrapolated to infinity
      (AUCinf ) and the maximum plasma concentration (Cmax ) significantly. The
      elimination half-life (T1/2 ) did not differ between the fasted and the fed
      states. For dose proportionality, nonproportional increases in AUCinf and Cmax at
      1-4 mg/kg doses were detected by a power model analysis.

PMID- 29352475
TI  - Characteristics of proanthocyanidins in leaves of Chamaecyparis obtusa var.
      formosana as strong alpha-glucosidase inhibitors.
AB  - BACKGROUND: In recent decades, there has been a growing demand for natural
      products with a view to using them as alpha-glucosidase inhibitors for reducing
      postprandial hyperglycemia. In this study, the hot water extract (HWE) from
      Chamaecyparis obtusa var. formosana (Hayata) Rehder (Cupressaceae) leaves and its
      soluble fractions were screened for alpha-glucosidase inhibition properties. The
      n-butanol-soluble fraction of HWE was further fractionated into 14 subfractions
      (B1-B14) using a Sephadex LH-20 column. The alpha-glucosidase-inhibitory
      activities and proanthocyanidin contents of all subfractions were determined. The
      structural characteristics of proanthocyanidins in proanthocyanidin-rich
      fractions were also elucidated. RESULTS: HWE produced a dose-dependent inhibition
      of alpha-glucosidase at low dose. Its IC50 value was 1.4 ug mL-1 , showing high
      inhibitory activity. Subfractions B7-B14 displayed powerful alpha-glucosidase
      inhibitory activities with IC50 values ranging between 1 and 0.015 ug mL-1 and
      contained abundant proanthocyanidins exceeding 300 mg g-1 . The proanthocyanidins
      with higher mean degree of polymerization (mDP), higher proportions of
      procyanidin dimer (A1 or A2) and (epi)afzelechin of extension units and a lower
      proportion of epicatechin of terminal units displayed high alpha-glucosidase
      inhibitory activities. CONCLUSION: Proanthocyanidins in HWE were viewed as
      potential natural alpha-glucosidase inhibitors for decreasing postprandial
      hyperglycemia. The results indicated that specific structural characteristics of
      proanthocyanidins would be required for alpha-glucosidase-inhibitory activity.
      (c) 2018 Society of Chemical Industry.

PMID- 29352476
TI  - Pharmacokinetic profiles of the active metamizole metabolites after four
      different routes of administration in healthy dogs.
AB  - Metamizole (MT), an analgesic and antipyretic drug, is rapidly hydrolyzed to the
      active primary metabolite 4-methylaminoantipyrine (MAA) and relatively active
      secondary metabolite 4-aminoantipyrine (AA). The aim of this study was to assess
      the pharmacokinetic profiles of MAA and AA after dose of 25 mg/kg MT by
      intravenous (i.v.), intramuscular (i.m.), oral (p.o.), and rectal (RC) routes in
      dogs. Six dogs were randomly allocated to an open, single-dose, four-treatment,
      four-phase, unpaired, crossover study design. Blood was collected at
      predetermined times within 24 hr, and plasma was analyzed by a validated HPLC-UV
      method. Plasma concentrations of MAA and AA after i.v., i.m., p.o., and RC
      administrations of MT were detectable from 5 (i.v. and i.m.) or 30 (p.o. and RC)
      min to 24 hr in all dogs. The highest concentrations of MAA were found in the
      i.v., then i.m., p.o., and RC groups. Plasma concentrations of AA were similar
      for i.v., i.m., and RC, and the concentrations were approximately double those in
      the PO groups. The AUCEV/IV ratio for MAA was 0.75 +/- 0.11, 0.59 +/- 0.08, and
      0.32 +/- 0.05, for i.m., p.o., and RC, respectively. The AUCEV/IV ratio for AA
      was 1.21 +/- 0.33, 2.17 +/- 0.62, and 1.08 +/- 0.19, for i.m., p.o., and RC,
      respectively. Although further studies are needed, rectal administration seems to
      be the least suitable route of administration for MT in the dog.

PMID- 29352477
TI  - Benzodiazepines for antipsychotic-induced tardive dyskinesia.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a disfiguring movement disorder, often of
      the orofacial region, frequently caused by using antipsychotic drugs. A wide
      range of strategies have been used to help manage TD, and for those who are
      unable to have their antipsychotic medication stopped or substantially changed,
      the benzodiazepine group of drugs have been suggested as a useful adjunctive
      treatment. However, benzodiazepines are very addictive. OBJECTIVES: To determine
      the effects of benzodiazepines for antipsychotic-induced tardive dyskinesia in
      people with schizophrenia, schizoaffective disorder, or other chronic mental
      illnesses. SEARCH METHODS: On 17 July 2015 and 26 April 2017, we searched the
      Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial
      registers), inspected references of all identified studies for further trials and
      contacted authors of each included trial for additional information. SELECTION
      CRITERIA: We included all randomised controlled trials (RCTs) focusing on people
      with schizophrenia (or other chronic mental illnesses) and antipsychotic-induced
      TD that compared benzodiazepines with placebo, no intervention, or any other
      intervention for the treatment of TD. DATA COLLECTION AND ANALYSIS: We
      independently extracted data from the included studies and ensured that they were
      reliably selected, and quality assessed. For homogenous dichotomous data, we
      calculated random effects, risk ratio (RR), and 95% confidence intervals (CI). We
      synthesised continuous data from valid scales using mean differences (MD). For
      continuous outcomes, we preferred endpoint data to change data. We assumed that
      people who left early had no improvement. MAIN RESULTS: The review now includes
      four trials (total 75 people, one additional trial since 2006, 21 people)
      randomising inpatients and outpatients in China and the USA. Risk of bias was
      mostly unclear as reporting was poor. We are uncertain about all the effects as
      all evidence was graded at very low quality. We found no significant difference
      between benzodiazepines and placebo for the outcome of 'no clinically important
      improvement in TD' (2 RCTs, 32 people, RR 1.12, 95% CI 0.60 to 2.09, very low
      quality evidence). Significantly fewer participants allocated to clonazepam
      compared with phenobarbital (as active placebo) experienced no clinically
      important improvement (RR 0.44, 95% CI 0.20 to 0.96, 1 RCT, 21 people, very low
      quality evidence). For the outcome 'deterioration of TD symptoms,' we found no
      clear difference between benzodiazepines and placebo (2 RCTs, 30 people, RR 1.48,
      95% CI 0.22 to 9.82, very low quality evidence). All 10 participants allocated to
      benzodiazepines experienced any adverse event compared with 7/11 allocated to
      phenobarbital (RR 1.53, 95% CI 0.97 to 2.41, 1 RCT, 21 people, very low quality
      evidence). There was no clear difference in the incidence of participants leaving
      the study early for benzodiazepines compared with placebo (3 RCTs, 56 people, RR
      2.73, 95% CI 0.15 to 48.04, very low quality evidence) or compared with
      phenobarbital (as active placebo) (no events, 1 RCT, 21 people, very low quality
      evidence). No trials reported on social confidence, social inclusion, social
      networks, or personalised quality of life, which are outcomes designated
      important by patients. No trials comparing benzodiazepines with placebo or
      treatment as usual reported on adverse effects. AUTHORS' CONCLUSIONS: There is
      only evidence of very low quality from a few small and poorly reported trials on
      the effect of benzodiazepines as an adjunctive treatment for antipsychotic
      induced TD. These inconclusive results mean routine clinical use is not indicated
      and these treatments remain experimental. New and better trials are indicated in
      this under-researched area; however, as benzodiazepines are addictive, we feel
      that other techniques or medications should be adequately evaluated before
      benzodiazepines are chosen.

PMID- 29352478
TI  - Effects of neuroimmune axis modulation by aprepitant on antipruritic and global
      disease severity in patients with cutaneous T-cell lymphoma.

PMID- 29352479
TI  - Contrasting effects of specialist and generalist herbivores on resistance
      evolution in invasive plants.
AB  - Invasive alien plants are likely to be released from specialist herbivores and at
      the same time encounter biotic resistance from resident generalist herbivores in
      their new ranges. The Shifting Defense hypothesis predicts that this will result
      in evolution of decreased defense against specialist herbivores and increased
      defense against generalist herbivores. To test this, we performed a comprehensive
      meta-analysis of 61 common garden studies that provide data on resistance and/or
      tolerance for both introduced and native populations of 32 invasive plant
      species. We demonstrate that introduced populations, relative to native
      populations, decreased their resistance against specialists, and increased their
      resistance against generalists. These differences were significant when
      resistance was measured in terms of damage caused by the herbivore, but not in
      terms of performance of the herbivore. Furthermore, we found the first evidence
      that the magnitude of resistance differences between introduced and native
      populations depended significantly on herbivore origin (i.e., whether the test
      herbivore was collected from the native or non-native range of the invasive
      plant). Finally, tolerance to generalists was found to be higher in introduced
      populations, while neither tolerance to specialists nor that to simulated
      herbivory differed between introduced and native plant populations. We conclude
      that enemy release from specialist herbivores and biotic resistance from
      generalist herbivores have contrasting effects on resistance evolution in
      invasive plants. Our results thus provide strong support for the Shifting Defense
      hypothesis.

PMID- 29352481
TI  - Aprepitant did not modify global disease activity in cutaneous T-cell lymphomas.

PMID- 29352480
TI  - Temporal heterogeneity increases with spatial heterogeneity in ecological
      communities.
AB  - Heterogeneity is increasingly recognized as a foundational characteristic of
      ecological systems. Under global change, understanding temporal community
      heterogeneity is necessary for predicting the stability of ecosystem functions
      and services. Indeed, spatial heterogeneity is commonly used in alternative
      stable state theory as a predictor of temporal heterogeneity and therefore an
      early indicator of regime shifts. To evaluate whether spatial heterogeneity in
      species composition is predictive of temporal heterogeneity in ecological
      communities, we analyzed 68 community data sets spanning freshwater and
      terrestrial systems where measures of species abundance were replicated over
      space and time. Of the 68 data sets, 55 (81%) had a weak to strongly positive
      relationship between spatial and temporal heterogeneity, while in the remaining
      communities the relationship was weak to strongly negative (19%). Based on a
      mixed model analysis, we found a significant but weak overall positive
      relationship between spatial and temporal heterogeneity across all data sets
      combined, and within aquatic and terrestrial data sets separately. In addition,
      lifespan and successional stage were negatively and positively related to
      temporal heterogeneity, respectively. We conclude that spatial heterogeneity may
      be a predictor of temporal heterogeneity in ecological communities, and that this
      relationship may be a general property of many terrestrial and aquatic
      communities.

PMID- 29352482
TI  - Influence of pharmacogenetic polymorphisms and demographic variables on metformin
      pharmacokinetics in an admixed Brazilian cohort.
AB  - AIMS: To identify pharmacogenetic and demographic variables that influence the
      systemic exposure to metformin in an admixed Brazilian cohort. METHODS: The
      extreme discordant phenotype was used to select 106 data sets from nine metformin
      bioequivalence trials, comprising 256 healthy adults. Eleven single-nucleotide
      polymorphisms in SLC22A1, SLC22A2, SLC47A1 SLC47A2 and in transcription factor
      SP1 were genotyped and a validated panel of ancestry informative markers was used
      to estimate the individual proportions of biogeographical ancestry. Two-step
      (univariate followed by multivariate) regression modelling was developed to
      identify covariates associated with systemic exposure to metformin, accessed by
      the area under the plasma concentration-time curve, between 0 and 48 h (AUC0-48h
      ), after single oral doses of metformin (500 or 1000 mg). RESULTS: The individual
      proportions of African, Amerindian and European ancestry varied widely, as
      anticipated from the structure of the Brazilian population The dose-adjusted, log
      transformed AUC0-48h 's (ng h ml-1  mg-1 ) differed largely in the two groups at
      the opposite ends of the distribution histogram, namely 0.82, 0.79-0.85 and 1.08,
      1.06-1.11 (mean, 95% confidence interval; P = 6.10-26 , t test). Multivariate
      modelling revealed that metformin AUC0-48h increased with age, food and carriage
      of rs12208357 in SLC22A1 but was inversely associated with body surface area and
      individual proportions of African ancestry. CONCLUSIONS: A pharmacogenetic marker
      in OCT1 (SLC22A1 rs12208357), combined with demographic covariates (age, body
      surface area and individual proportion of African ancestry) and a food effect
      explained 29.7% of the variability in metformin AUC0-48h .

PMID- 29352483
TI  - Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis
      bullosa and epidermolysis bullosa acquisita.
AB  - Type VII collagen (COL7), a major component of anchoring fibrils in the epidermal
      basement membrane zone, has been characterized as a defective protein in
      dystrophic epidermolysis bullosa and as an autoantigen in epidermolysis bullosa
      acquisita. Although COL7 is produced and secreted by both epidermal keratinocytes
      and dermal fibroblasts, the role of COL7 with regard to the epidermis is rarely
      discussed. This review focuses on COL7 physiology and pathology as it pertains to
      epidermal keratinocytes. We summarize the current knowledge of COL7 production
      and trafficking, its involvement in keratinocyte dynamics, and epidermal
      carcinogenesis in COL7 deficiency and propose possible solutions to unsolved
      issues in this field.

PMID- 29352485
TI  - Nonclassical monocytes: are they the next therapeutic targets in multiple
      sclerosis?

PMID- 29352484
TI  - Melatonin ameliorates Abeta42 -induced alteration of betaAPP-processing
      secretases via the melatonin receptor through the Pin1/GSK3beta/NF-kappaB pathway
      in SH-SY5Y cells.
AB  - Melatonin is involved in the physiological regulation of the beta-amyloid
      precursor protein (betaAPP)-cleaving secretases which are responsible for
      generation of the neurotoxic amyloid beta (Abeta) peptide, one of the hallmarks
      of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the
      underlying mechanisms of this regulation under pathological conditions. We
      establish that melatonin prevents Abeta42 -induced downregulation of a
      disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well
      as upregulation of beta-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1)
      in SH-SY5Y cell cultures. We also demonstrate that the intrinsic mechanisms of
      the observed effects occurred via regulation of nuclear factor kappa-light-chain
      enhancer of activated B cells (NF-kappaB) and glycogen synthase kinase (GSK)
      3beta as melatonin reversed Abeta42 -induced upregulation and nuclear
      translocation of NF-kappaBp65 as well as activation of GSK3beta via its receptor
      activation. Furthermore, specific blocking of the NF-kappaB and GSK3beta pathways
      partially abrogated the Abeta42 -induced reduction in the BACE1 and PS1 levels.
      In addition, GSK3beta blockage affected alpha-secretase cleavage and modulated
      nuclear translocation of NF-kappaB. Importantly, our study for the first time
      shows that peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is a
      crucial target of melatonin. The compromised levels and/or genetic variation of
      Pin1 are associated with age-dependent tau and Abeta pathologies and neuronal
      degeneration. Interestingly, melatonin alleviated the Abeta42 -induced reduction
      of nuclear Pin1 levels and preserved the functional integrity of this isomerase.
      Our findings illustrate that melatonin attenuates Abeta42 -induced alterations of
      betaAPP-cleaving secretases possibly via the Pin1/GSK3beta/NF-kappaB pathway.

PMID- 29352486
TI  - Adverse effects of amphotericin B in children; a retrospective comparison of
      conventional and liposomal formulations.
AB  - AIMS: Lipid formulations of amphotericin B, rather than conventional amphotericin
      (c-amB), are increasingly used despite limited data comparing these preparations
      in children. Data on the incidence of adverse effects with amphotericin B at
      standard doses are scarce. This study aimed to compare the adverse effects
      associated with standard doses of c-amB and liposomal amphotericin (l-amB) in
      children. METHODS: Children admitted to the Royal Children's Hospital Melbourne
      and treated with c-amB or l-amB between January 2010 and September 2013 were
      included. Clinical and laboratory data were retrospectively extracted from
      medical records to compare amphotericin-related infusion reactions,
      nephrotoxicity (glomerulotoxicity and tubulopathy) and hepatotoxicity. RESULTS:
      Seventy-six children received c-amB and 39 received l-amB. Standard drug
      administration (recommended dose and infusion time) occurred in 74% (56/76) of
      patients on c-amB and 85% (33/39) on l-amB. In these 89 children, infusion
      related reactions were similar for both c-amB and l-amB (23% (13/56) vs. 9%
      (3/33); P = 0.15); none occurred in children aged <90 days. There was no
      difference in amphotericin-associated glomerulotoxicity (c-amB 14% (8/56) vs. l
      amB 21% (7/33); P = 0.40) or in the median maximum potassium requirements (c-amB
      3.1 vs. l-amB 2.3 mmol kg-1  d-1 ; P = 0.29). Hepatotoxicity occurred more
      frequently with l-amB than c-amB (83% (24/29) vs. 56% (20/36); P = 0.032).
      CONCLUSIONS: When appropriately administered, l-amB was associated with more
      hepatotoxicity than c-amB, with no difference in infusion-related reactions or
      nephrotoxicity. Differences in adverse effects between the preparations is not as
      marked in children as reported in adults.

PMID- 29352487
TI  - Disaccharide combinations and the expression of enolase3 and plasma membrane Ca2+
      ATPase isoform in sturgeon sperm cryopreservation.
AB  - Acipenser sinensis and Acipenser dabryanus are critically endangered species, so
      germplasm conservation via cryopreservation of sperm is necessary. Disaccharides
      can act as membrane-impermeable cryoprotectants, and enolase3 (ENO3) and plasma
      membrane Ca2+ ATPase isoform (PMCA2) are proteins associated with sperm quality.
      We considered seven characteristics of sperm quality in cultured brood stock from
      A. sinensis and A. dabryanus. We tested use of sucrose or trehalose alone and in
      combination at different concentrations for cryopreservation of A. dabryanus
      sperm. A low concentration of sucrose plus trehalose (S15 T15 ) was optimal.
      Mixing of the extender with sucrose, lactose, or trehalose alone or with pairwise
      mixtures revealed that a mixture of lactose and trehalose (L15 T15 ) gave the
      best results for both A. sinensis and A. dabryanus. Enolase3 and PMCA2 expression
      levels were measured in cryopreserved A. sinensis sperm via Western blotting.
      Relative ENO3 and PMCA2 expression levels were examined, and the relationship
      between disaccharide composition, sperm quality and protein expression was
      explored in A. sinensis. The results showed that relative ENO3 and PMCA2
      expression levels were the highest at L15 T15 in cryopreserved A. sinensis sperm.
      There were significant positive correlations between ENO3 expression and
      percentage membrane integrity, and between PMCA2 expression and sperm motility
      parameters (percentage of motile sperm, curvilinear velocity, straight-line
      velocity and average path velocity; p < .05) in cryopreserved A. sinensis sperm.
      Our results indicate the optimal disaccharide combination and concentrations for
      cryopreservation of A. sinensis and A. dabryanus sperm and suggest that ENO3 and
      PMCA2 expression levels could serve as a valuable indicator of sperm quality in
      A. sinensis.

PMID- 29352489
TI  - Prospective questionnaire study showed that higher self-efficacy predicted longer
      exclusive breastfeeding by the mothers of late preterm infants.
AB  - AIM: An important variable that influences breastfeeding outcomes is how
      confident a woman feels about her ability to breastfeed successfully at an early
      stage. We investigated breastfeeding self-efficacy in the mothers of late preterm
      infants. METHODS: This was a prospective, comparative study that focused on
      mothers who had delivered babies at 34 + 0 to 36 + 6 weeks and were recruited in
      2012-2015 from a neonatal intensive care unit and a postnatal ward at a Swedish
      university hospital. The Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF)
      was used to psychometrically assess the mothers at 40 weeks of postmenstrual age
      (n = 148) and at three months of corrected age (n = 114). RESULTS: The BSES-SF
      scores were higher in the 87% of mothers that exclusively breastfed when their
      babies reached 40 weeks (57.1 out of 70) than those who did not (41.4, p <
      0.001), indicating better self-efficacy. The figures remained higher in the 68%
      of exclusive breastfeeding mothers at three months of corrected age (60.9 versus
      51.7). CONCLUSION: Self-efficacy was an important predictor of the length of
      breastfeeding in mothers of late preterm infants, and the BSES-SF can be used to
      detect low self-efficacy that could lead to early breastfeeding cessation.

PMID- 29352488
TI  - Understanding intratumor heterogeneity by combining genome analysis and
      mathematical modeling.
AB  - Cancer is composed of multiple cell populations with different genomes. This
      phenomenon called intratumor heterogeneity (ITH) is supposed to be a fundamental
      cause of therapeutic failure. Therefore, its principle-level understanding is a
      clinically important issue. To achieve this goal, an interdisciplinary approach
      combining genome analysis and mathematical modeling is essential. For example, we
      have recently performed multiregion sequencing to unveil extensive ITH in
      colorectal cancer. Moreover, by employing mathematical modeling of cancer
      evolution, we demonstrated that it is possible that this ITH is generated by
      neutral evolution. In this review, we introduce recent advances in a research
      field related to ITH and also discuss strategies for exploiting novel findings on
      ITH in a clinical setting.

PMID- 29352490
TI  - Oral lichenoid reaction showing multiple ulcers associated with anti-programmed
      death cell receptor-1 treatment: A report of two cases and published work review.
AB  - Anti-programmed cell death receptor-1 (PD-1) antibodies represent an effective
      treatment opinion for advanced melanoma and non-small-cell lung cancer, as well
      as other cancerous entities. Immune checkpoint inhibitors such as anti-PD-1
      antibody result in a unique side-effect profile, commonly described as immune
      related adverse events (irAE). These irAE affect the skin, gastrointestinal
      tract, liver, endocrine system and other organ systems. We report two cases of
      oral lichenoid reaction showing multiple ulcers associated with nivolumab
      treatment. Both patients presented with multiple ulcers covered with fibrinous
      plaque over the entire oral mucosa, lips and tongue. Histopathological
      examination of ulceration showed epithelial necrosis and subepidermal clefts with
      dense band-like layers of lymphohistiocytic infiltrate within the upper dermis.
      Nivolumab was interrupted in both cases. Case 1 responded well to topical
      corticosteroids. Case 2 required oral corticosteroids, however, nivolumab could
      be restarted without recurrence of oral ulcers. We provide a comprehensive review
      of reported cases of lichenoid reaction showing multiple oral ulcers associated
      with anti-PD-1 therapy to date. Early recognition and management may improve
      treatment, avoid discontinuation of life-saving therapy and maintain quality of
      life in these patients.

PMID- 29352491
TI  - Continuous glucose monitoring in pregnant women with Type 1 diabetes: benefits
      for mothers, using pumps or pens, and their babies.
AB  - AIMS: To review the current literature on the use of continuous glucose
      monitoring during pregnancy in women with Type 1 diabetes. METHODS: We searched
      the literature for randomized controlled trials using continuous glucose
      monitoring during pregnancy in women with Type 1 diabetes. RESULTS: Three
      randomized trials were found and discussed in this review. One UK study found a
      reduction in large-for-gestational-age infants; however, only masked continuous
      glucose monitoring was used in that study. A Danish study used intermittent real
      time continuous glucose monitoring and found no differences. The present authors
      conducted the CONCEPTT trial, in which pregnant women and women planning
      pregnancy were randomized to receive continuous glucose monitoring or standard
      care. We found a greater drop in HbA1c , more time spent in the target range, and
      a reduction in some adverse neonatal outcomes in women using continuous glucose
      monitoring. Numbers-needed-to-treat to prevent a large-for-gestational-age
      infant, a neonatal intensive care unit admission for >24 h, and a neonatal
      hypoglycaemia event were low. These findings were seen in both injection and pump
      users and across all countries. Possible reasons for differences in study
      findings are discussed. In addition, several issues need further study. Glycaemic
      variability and differences in dietary intake may also have played a role.
      Despite excellent glycaemic control, babies continue to be large. More research
      is needed to understand the role of glucose targets and the dynamic placental
      processes involved in fetal growth. CONCLUSIONS: The use of continuous glucose
      monitoring in women with Type 1 diabetes in pregnancy is associated with improved
      glycaemic control and neonatal outcomes. Further research examining the glycaemic
      and non-glycaemic variables involved in fetal growth and the cost-benefit of
      using continuous glucose monitoring in pregnancy is warranted.

PMID- 29352492
TI  - Variability of pulsed energy outputs from three dermatology lasers during
      multiple simulated treatments.
AB  - BACKGROUND: Dermatology laser treatments are undertaken at regional departments
      using lasers of different powers and wavelengths. In order to achieve good
      outcomes, there needs to be good consistency of laser output across different
      weeks as it is custom and practice to break down the treatments into individual
      fractions. Departments will also collect information from test patches to help
      decide on the most appropriate treatment parameters for individual patients.
      OBJECTIVES: The objective of these experiments is to assess the variability of
      the energy outputs from a small number of lasers across multiple weeks at
      realistic parameters. METHODS: The energy outputs from 3 lasers were measured at
      realistic treatment parameters using a thermopile detector across a period of 6
      weeks. RESULTS: All lasers fired in single-pulse mode demonstrated good
      repeatability of energy output. In spite of one of the lasers being scheduled for
      a dye canister change in the next 2 weeks, there was good energy matching between
      the two devices with only a 4%-5% variation in measured energies. CONCLUSIONS:
      Based on the results presented, clinical outcomes should not be influenced by
      variability in the energy outputs of the dermatology lasers used as part of the
      treatment procedure.

PMID- 29352493
TI  - Effect of dietary manipulation and vaccination of turkey breeder hens on
      immunoglobulin levels of yolk, yolk sac and neonate poults.
AB  - Two hundred turkey breeder hens and 24 viable toms of 30-35 weeks age of small
      white variety were distributed into two treatment groups having four replicates
      of 25 hens and three toms in each treatment. First four replicates were offered a
      turkey breeder diet (Diet A) (Nutrient requirements of poultry, 1994, National
      Academic Press, Washington, DC) and the rest four replicates were maintained on a
      higher plane of nutrition (Diet B) for 8-week duration. After 6 weeks of
      experimental feeding, two replicates from each treatment groups were vaccinated
      with ND (R2 B) vaccine. Yolk sac of embryo from birds fed Diet B had a
      significantly higher (p < .05) IgG, IgM level and HI titre (log 2) than those fed
      Diet A. HI titre values of embryonic yolk sac from the vaccinated birds fed Diet
      B were significantly higher (p < .05) than that of the control groups. In
      addition, HI titre values were significantly higher (p < .05) in the day-old
      poults of the birds fed Diet B than that of those fed Diet A. There was
      significantly (p < .01) positive correlation between serum IgG and IgM of the
      breeder birds and day-old chicks. Similarly, there was significantly (p < .05)
      positive correlation between yolk IgG and IgM after 1-month experimental feeding
      and yolk sac IgG and IgM. Positive correlation (p < .05) also existed between
      yolk sac IgM and day-old chick serum IgM. Furthermore, the HI titres of breeder
      birds' serum at 14 days post-vaccination were positively correlated with their
      egg yolk after 10 and 15 days post-vaccination, yolk sac and day-old chicks.
      Thus, the study envisaged that a higher immunity in neonate poults from turkey
      breeders maintained on a higher plane of nutrition may be elicited as there was
      maternal transfer of antibodies from the serum of breeder birds to their
      offsprings through their yolk sac.

PMID- 29352494
TI  - The effects of late gestation nutrient restriction of dams on beef heifer intake,
      metabolites and hormones during an ad libitum feeding trial.
AB  - This study's objective was to determine if nutrient restriction during late
      gestation affected beef heifer feed intake, body weight (BW) gain and endocrine
      regulation during a 10-week feeding trial. During the last 100 days of gestation,
      control (CON) dams were fed to increase body condition score (BCS). Whereas,
      nutrient-restricted dams (NR) and NR dams protein supplemented 3 days/week (NRS)
      were fed to decrease BCS by 1.2. After parturition, all cow-calf pairs were moved
      to a common pasture and fed in excess of requirements until weaning. At 15 months
      of age, heifers were randomly sorted into two pens and adjusted to a commercial
      total mixed ration over a 2-week period. Blood samples and BW were taken at the
      initiation of feeding and on a biweekly basis for the duration of the feeding
      trial. Feed intake was monitored for 10 weeks using a GrowSafe System. After 10
      weeks, an intravenous glucose tolerance test (IVGTT) was performed on 21 randomly
      subsampled heifers. During the feeding trial, NR heifers consumed more feed than
      CON and NRS heifers. Heifers from NR dams tended to increase BW compared to NRS
      and CON heifers when adjusted for initial BW. Heifers from NR and NRS dams had a
      greater increase in BCS compared to heifers from CON dams. Plasma glucose and
      insulin concentrations during the feeding trial increased in NR heifers compared
      to the other groups beginning at 2 and 4 weeks respectively. Plasma leptin
      concentrations were increased in the NR and NRS heifers compared to the CON
      heifers beginning at week 4 of feeding. During the IVGTT at the conclusion of the
      feeding challenge, plasma glucose and insulin were increased in NR heifers
      compared to other treatment groups. These results show that nutrient restriction
      during late gestation alters appetite and endocrine regulation in heifer
      offspring.

PMID- 29352495
TI  - Ultrasonographic-based predictive factors influencing successful return to racing
      after superficial digital flexor tendon injuries in flat racehorses: A
      retrospective cohort study in 469 Thoroughbred racehorses in Hong Kong.
AB  - BACKGROUND: Superficial digital flexor tendon (SDFT) injury is an important
      health and welfare concern in racehorses. It is generally diagnosed with
      ultrasonography, but predictive ultrasonographic features have not been reported.
      OBJECTIVES: To determine ultrasonographic features of forelimb SDFT injury at
      initial presentation in Thoroughbred racehorses that could predict a successful
      return to racing (completing >=5 races). STUDY DESIGN: Retrospective cohort
      study. METHODS: Digitised ultrasonographic images of 469 horses with forelimb
      SDFT injuries from the Hong Kong Jockey Club (2003-2014) were evaluated, using a
      previously validated ultrasonographic scoring system. Six ultrasonographic
      parameters were evaluated (type and extent of the injury, location, echogenicity,
      cross-sectional area and longitudinal fibre pattern of the maximal injury zone
      [MIZ]), as well as horse signalment, retirement date and number of races before
      and after injury. Data were analysed by generalised linear regression with
      significance at P<0.05. RESULTS: Cases were divided into two groups: 1) For cases
      of SDFT tendonitis with core lesions, cross-sectional area at the MIZ was the
      most significant factor determining a successful return to racing (P = 0.03). If
      the lesion was <50% of the total cross-sectional area, horses had 29-35%
      probability of successfully racing again, but if it was >=50% this decreased to
      11-16%. 2) For cases of SDFT tendonitis without a core lesion, longitudinal fibre
      pattern at the MIZ best predicted a successful return to racing (P = 0.002); if
      the affected longitudinal fibre pattern was <75% of the total, horses had 49-99%
      probability of successfully return to racing, but if it was >=75% this decreased
      to 14%. MAIN LIMITATIONS: Prognostic information may not be applicable to other
      breeds/disciplines. CONCLUSIONS: This is the first study to describe
      ultrasonographic features of forelimb SDFT injuries at initial presentation that
      were predictive of successful return to racing. The outcomes will assist with
      early, evidence-based decisions on prognosis in Thoroughbred racehorses.

PMID- 29352496
TI  - Microcystic adnexal carcinoma with sebaceous differentiation: Three cases.
AB  - Microcystic adnexal carcinoma (MAC) is a low-grade malignant tumor of the skin.
      Histologically, this tumor shows a biphasic pattern, with cords and nests of
      basaloid cells, as well as keratin horn cysts. This biphasic histological
      appearance has been interpreted by some authors as a sign of double eccrine and
      folliculosebaceous-apocrine differentiation, whereas some other authors defend a
      solely eccrine differentiation. In this context, sebaceous differentiation in MAC
      would support the first option. However, there are only 3 cases of MAC with
      sebaceous differentiation in the literature, and all of them were reported before
      adipophilin was available, which in the appropriate context (eg, testing clear
      cells for sebaceous vs eccrine differentiation) is very useful. In this study, we
      present 3 cases of MAC with focal sebaceous differentiation confirmed by
      immunoexpression of adipophilin in the sebaceous foci.

PMID- 29352497
TI  - Redox potential: An intrinsic parameter of the rumen environment.
AB  - The ruminal ecosystem is a fermentative milieu which is interesting to discuss in
      terms of its redox status as a reflection of an intense bacterial activity. The
      objective of this systematic literature review is to quantitatively analyze data
      collected on redox potential (Eh) in the rumen and to explore relationship
      between ruminal Eh, nature of the diet fed to ruminants, and ruminal fermentation
      parameters. Data obtained from 15 studies comprising 24 different diets was used
      in the analysis. Studies included in the data file were selected based on the
      criteria of: (i) the nature of the reference electrode was specified, (ii) the
      ruminal Eh was recorded simultaneously to pH, (iii) animal body weight (BW) and
      dry matter intake (DMI) were reported and (iv) the composition of the diet was
      precisely described. Results showed a high variability in ruminal Eh values.
      However, all recorded values are markedly negative reflecting the absence of
      oxygen and the strong reducing power of the rumen environment. The main factors
      contributing to the variation were the method of Eh measurement and the nature of
      the diet fed to ruminants. Redox potential was positively correlated with DMI and
      proportion of concentrate in the diet, and tended to be positively correlated
      with soluble carbohydrates content. In contrast, it was negatively correlated
      with neutral detergent fibre from forages. The hierarchical ascendant
      classification discriminated two groups of diets leading to significant change in
      ruminal Eh level. Ruminal Eh was negatively correlated with pH, total volatile
      fatty acids produced and proportion of acetate, and positively correlated with
      proportion of propionate. This review revealed Eh to be dependent on the diet
      composition and DMI, at least within the range of diets included in the database.

PMID- 29352498
TI  - Autofocusing-based phase correction.
AB  - PURPOSE: Phase artifacts due to B0 inhomogeneity can severely degrade the quality
      of MR images. The artifacts are particularly prominent in long-TE scans and
      usually appear as ghosting and blur. We propose a retrospective phase correction
      method based on autofocusing. The proposed method uses raw data acquired with
      standard imaging sequences, and does not rely on navigators or external measures
      of field inhomogeneity. METHODS: We formulate and solve the optimization problem,
      where we seek the latent phase offsets that are associated with an optimal value
      of the image quality measure that is evaluated in the spatial domain. As a
      quality measure we use entropy computed on spatial image gradients. We propose
      two types of objective function, both compatible with parallel imaging and
      accelerated image acquisition. RESULTS: We evaluate the method on both synthetic
      and real data. In real data case we evaluate the performance on a range of
      sequences and images acquired with different acceleration factors. The
      experimental results demonstrate that our method is capable of minimizing
      ghosting artifacts and that the quality of the output images is similar to
      navigator-based reconstructions. CONCLUSION: The presented technique can be
      alternative to or complement navigator-based methods, and is able to improve
      images with severe phase artifacts from all standard imaging sequences. Magn
      Reson Med 80:958-968, 2018. (c) 2018 International Society for Magnetic Resonance
      in Medicine.

PMID- 29352499
TI  - 2016 measles outbreak in Japan: A report of two cases with reappraisal of
      histological features.

PMID- 29352500
TI  - Characterization of skin blister fluids from children with Epstein-Barr virus
      associated lymphoproliferative disease.
AB  - Epstein-Barr virus (EBV)-associated T- or natural killer (NK)-cell
      lymphoproliferative disease (LPD) is a heterogeneous group of disorders
      characterized by chronic proliferation of EBV-infected lymphocytes. Patients may
      present with severe skin manifestations, including hypersensitivity to mosquito
      bites (HMB) and hydroa vacciniforme (HV)-like eruption, which are characterized
      by blister formation and necrotic ulceration. Skin biopsy specimens show
      inflammatory reactions comprising EBV-infected lymphocytes. However, blister
      fluids have not been fully assessed in patients with this disease. Blister fluids
      were collected from three patients with EBV-associated LPD: two with HMB and one
      with HV. Immunophenotyping of blister lymphocytes and measurement of tumor
      necrosis factor (TNF)-alpha in blister fluids were performed. The patients with
      HMB and HV exhibited markedly increased percentages of NK and gammadelta T cells,
      respectively, in both peripheral blood and blister fluids. These NK and
      gammadelta T cells strongly expressed the activation marker human leukocyte
      antigen-DR and were considered to be cellular targets of EBV infections. TNF
      alpha was highly elevated in all blister fluids. Severe local skin reactions of
      EBV-associated LPD may be associated with infiltrating EBV-infected lymphocytes
      and a high TNF-alpha concentration in blister fluids.

PMID- 29352501
TI  - Predictors of beef calf temperament at weaning and its impact on temperament at
      breeding and reproductive performance.
AB  - Two experiments were conducted to determine (i) factors influencing calf
      temperament at weaning, (ii) association between heifer-calf temperament at
      weaning and temperament at breeding and (iii) effect of heifer-calf temperament
      on pregnancy rate per artificial insemination (P/AI). In experiment 1, beef cows
      and their calves (n = 285) from three farms were used. Sire docility estimated
      progeny difference (EPD) score, birth type (normal or assisted), calf gender,
      calf behaviour (during 1st 4 weeks) and calf health status (until weaning) were
      recorded. Cows and calves were assigned a temperament score (0-calm; 1
      excitable), and all cows were given a body condition score (BCS, 1-9; 1
      emaciated; 9-obese) at weaning. Calf's illness (p < .05), low sire docility EPD
      score (p < .05), altered gait (p < .05), altered resting behaviour (p < .01),
      reduced/no play behaviour (p < .05) and cow excitable temperament (p < .001)
      increased calf excitable temperament at weaning. In experiment 2, replacement
      heifer-calves (n = 758) from 12 farms were assigned a temperament score at
      weaning and later at breeding. Blood from 40 calves at weaning and 31 heifers at
      initiation of synchronization (same animals) was collected by coccygeal
      venipuncture for determination of circulating cortisol and substance P
      concentrations. Heifers were assigned a BCS and reproductive tract score (RTS, 1
      5; 1-immature, acyclic; 5-mature, cyclic), synchronized for fixed time AI,
      observed for oestrus and were artificially inseminated. Cortisol concentrations
      were increased in excitable heifer-calves compared to calm heifer-calves at
      weaning (p < .05), and substance P was increased in excitable compared to calm
      females both at weaning and breeding (p < .05). Low sire EPD docility score (p <
      .01), heifer-calf excitable temperament at weaning increased excitable
      temperament at breeding (p < .01). Controlling for BCS categories (p < .01),
      oestrous expression (p < .0001) and temperament at breeding by oestrous
      expression (p < .05), the calf's excitable temperament at weaning (p < .001)
      reduced P/AI (Calm, 62.7 (244/389) vs. Excitable, 53.4% (197/369); p < .01). In
      conclusion, selection of docile cows and sires with greater docility EPD score
      should be given consideration to reduce calf excitement. Temperament in beef
      female can be detected earlier in their life and could be used as a tool in the
      selection process and to improve their performances.

PMID- 29352502
TI  - Case of relapsing remitting neuro-Sweet disease mimicking immunoglobulin G4
      related disease.

PMID- 29352503
TI  - In vivo effects of MU-opioid receptor agonist/delta-opioid receptor antagonist
      peptidomimetics following acute and repeated administration.
AB  - BACKGROUND AND PURPOSE: Agonists at MU-opioid receptors (MU-receptors) are used
      for pain management but produce adverse effects including tolerance, dependence
      and euphoria. The co-administration of a MU-receptor agonist with a delta-opioid
      receptor (delta-receptor) antagonist has been shown to produce antinociception
      with reduced development of some side effects. We characterized the effects of
      three MU-receptor agonist/delta-receptor antagonist peptidomimetics in vivo after
      acute and repeated administration to determine if this profile provides a viable
      alternative to traditional opioid analgesics. EXPERIMENTAL APPROACH: Three MU
      receptor agonist / delta-receptor antagonist peptidomimetics, AAH8, AMB46 and
      AMB47, and morphine were evaluated for the development of tolerance and
      dependence after 5 days of twice daily treatment with escalating doses of drug
      (10-50 mg.kg-1 ). Antinociceptive effects were measured in the warm water tail
      withdrawal assay before and after repeated drug treatment. Physical dependence
      was evaluated by naltrexone-precipitated withdrawal jumping. The rewarding
      effects of AAH8 were evaluated using a conditioned place preference (CPP) assay
      with twice daily conditioning sessions performed for 5 days. KEY RESULTS:
      Morphine, AAH8, AMB47 and AMB46 all demonstrated acute antinociceptive effects,
      but repeated administration only produced tolerance in animals treated with
      morphine and AMB46. Injection of naltrexone precipitated fewer jumps in mice
      treated repeatedly with AAH8 as compared with morphine, AMB47 or AMB46.
      Conditioning with morphine, but not AAH8, produced significant CPP. CONCLUSIONS
      AND IMPLICATIONS: AAH8 may be a better alternative than traditional opioid
      analgesics, producing antinociception with less development of tolerance and
      dependence and may be less rewarding than morphine.

PMID- 29352504
TI  - Trophic niche, capture efficiency and venom profiles of six sympatric ant-eating
      spider species (Araneae: Zodariidae).
AB  - The arms race between specialist predators and their prey has resulted in the
      evolution of a variety of specific adaptations. In venomous predators, this can
      include venom composition, particularly if predators are specialized on dangerous
      prey. Here, we performed an integrative study using six species of highly
      specialized ant-eating spiders of the genus Zodarion to investigate their
      phylogeny, realized trophic niche, efficacy in the capture of various ant species
      and venom composition. Data on natural diet obtained by next-generation
      sequencing and field observations showed that the six Zodarion species exploit
      different ant species. Their phylogeny, based on mitochondrial and nuclear genes,
      correlated with the composition of their natural prey, indicating that closely
      related Zodarion species specialize on similar ant species. Prey-capture
      parameters differed among Zodarion species suggesting prey-specific efficacy.
      Similarly, the venom profiles of both low and high molecular compounds differed
      among species. Only the profiles of low molecular compounds were correlated with
      capture efficacy parameters, suggesting that the venom of Zodarion spiders
      contains prey-specific components. Our study suggests that Iberian Zodarion
      spiders are specialized on particular ant species.

PMID- 29352505
TI  - p53-independent Noxa induction by cisplatin is regulated by ATF3/ATF4 in head and
      neck squamous cell carcinoma cells.
AB  - The platinum-based DNA damaging agent cisplatin is used as a standard therapy for
      locally advanced head and neck squamous cell carcinoma (HNSCC). However, the
      mechanisms underpinning the cytotoxic effects of this compound are not entirely
      elucidated. Cisplatin produces anticancer effects primarily via activation of the
      DNA damage response, followed by inducing BCL-2 family dependent mitochondrial
      apoptosis. We have previously demonstrated that cisplatin induces the expression
      of proapoptotic BCL-2 family protein, Noxa, that can bind to the prosurvival BCL
      2 family protein, MCL-1, to inactivate its function and induce cell death. Here,
      we show that the upregulation of Noxa is critical for cisplatin-induced apoptosis
      in p53-null HNSCC cells. This induction is regulated at the transcriptional
      level. With a series of Noxa promoter-luciferase reporter assays, we find that
      the CRE (cAMP response element) in the promoter is critical for the Noxa
      induction by cisplatin treatment. Among the CREB/ATF transcription factors, ATF3
      and ATF4 are induced by cisplatin, and downregulation of ATF3 or ATF4 reduced
      cisplatin-induced Noxa. ATF3 and ATF4 bind to and cooperatively activate the Noxa
      promoter. Furthermore, ERK1 is involved in cisplatin-induced ATF4 and Noxa
      induction. In conclusion, ATF3 and ATF4 are important regulators that induce Noxa
      by cisplatin treatment in a p53-independent manner.

PMID- 29352506
TI  - Patterns of burns and scalds in Mongolian children: a hospital-based prospective
      study.
AB  - OBJECTIVE: To describe the circumstances of burn injury occurrence among
      Mongolian children and the products involved. METHODS: Study participants were
      children aged 15 years and younger who were admitted to the Burn Unit of the
      National Trauma Orthopedic Research Center from August 2015 to July 2016. We
      collected data on participant demographics and the aetiology and clinical
      features of their burn injuries, and we analysed the data based on the NOMESCO
      Classification model. FINDINGS: Of 906 children, 83% were aged 0-3 years, 66%
      were injured around the cooking area in the traditional tent-like dwelling called
      a ger or a detached house where no specified kitchen exists, and 28% were injured
      in a kitchen. Burn injuries resulted mostly from exposure to overflowing hot
      liquids (93%). Electric pots and electric kettles were the products most
      frequently involved in causing burn injuries (41% and 14%, respectively). Of 601
      major burn injuries, 52% were due to electric pots. Moreover, burn injuries
      inflicted by electric pots were most likely to be major burn injuries (83%).
      Children typically fell into electric pots, while electric kettles were often
      pulled down by children. CONCLUSION: Burn injuries among Mongolian children
      mainly occurred in cooking area of a ger involving electric pots. The current
      practice of cooking on the floor should be reconsidered for child burn
      prevention.

PMID- 29352507
TI  - Nuclear and membrane estrogen receptor antagonists induce similar mTORC2
      activation-reversible changes in synaptic protein expression and actin
      polymerization in the mouse hippocampus.
AB  - AIMS: Estrogens play pivotal roles in hippocampal synaptic plasticity through
      nuclear receptors (nERs; including ERalpha and ERbeta) and the membrane receptor
      (mER; also called GPR30), but the underlying mechanism and the contributions of
      nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is
      involved in actin cytoskeleton polymerization and long-term memory, but whether
      mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs is
      unclear. METHODS: We treated animals with nER antagonists (MPP/PHTPP) or the mER
      antagonist (G15) alone or in combination with A-443654, an activator of mTORC2.
      Then, we examined the changes in hippocampal SRC-1 expression, mTORC2 signaling
      (rictor and phospho-AKTSer473), actin polymerization (phospho-cofilin and
      profilin-1), synaptic protein expression (GluR1, PSD95, spinophilin, and
      synaptophysin), CA1 spine density, and synapse density. RESULTS: All of the
      examined parameters except synaptophysin expression were significantly decreased
      by MPP/PHTPP and G15 treatment. MPP/PHTPP and G15 induced a similar decrease in
      most parameters except p-cofilin, GluR1, and spinophilin expression. The ER
      antagonist-induced decreases in these parameters were significantly reversed by
      mTORC2 activation, except for the change in SRC-1, rictor, and synaptophysin
      expression. CONCLUSIONS: nERs and mER contribute similarly to the changes in
      proteins and structures associated with synaptic plasticity, and mTORC2 may be a
      novel target of hippocampal-dependent dementia such as Alzheimer's disease as
      proposed by previous studies.

PMID- 29352508
TI  - Inhibition of BRD4 attenuates cardiomyocyte apoptosis via NF-kappaB pathway in a
      rat model of myocardial infarction.
AB  - BACKGROUND: Myocardial infarction (MI) remains the most common cause of heart
      failure (HF) worldwide. For almost 50 years, HF has been recognized as a
      determinant of adverse prognosis after MI, but efforts to promote myocardial
      repair have failed to be translated into clinical therapies. AIMS: In this study,
      we investigated the effects of BRD4 on cardiac function and the underlying
      mechanism. MATERIAL AND METHODS: The in vivo rat model of AMI and in vitro
      neonatal cardiomyocytes were established and cultured respectively, the BRD4 and
      NPPA/NPPB expression levels were detected by qPCR and Western blot, and
      interaction of BRD4 with acetylation RelA or NPPA/B promoters were examined by co
      immunoprecipitation and chromatin immunoprecipitation assays, respectively.
      RESULTS: We found that BRD4 protein expression was significantly increased in
      cardiomyocytes of MI rat model and cardiomyocytes under hypoxia, accompanied by
      the expression of natriuretic peptide A (NPPA) and natriuretic peptide B (NPPB).
      Functionally, knockdown of BRD4 greatly downregulated the NPPA and NPPB in vivo
      and in vitro, improved the hemodynamic and biometric parameters in rat with heart
      failure, as well as decreased the apoptosis occurrence. In vitro studies further
      demonstrated that BRD4 bound with acetylated RelA to enhance the activation of NF
      kappab signaling, which resulted in activation of NPPA and NPPB transcriptions.
      CONCLUSIONS: Taken together, our findings suggest that inhibition of BRD4
      attenuated cardiomyocyte apoptosis via NF-kappaB pathway in myocardial
      infarction, and this study sheds light on developing new strategies to overcome
      myocardial damage.

PMID- 29352510
TI  - Identification of a novel HLA-C*12 allele, HLA-C*12:221.
AB  - HLA-C*12:221 differs from C*12:02:03 by a single nucleotide substitution at
      position 367 of exon 3.

PMID- 29352509
TI  - Molecular evidence to suggest pigeon-type Chlamydia psittaci in association with
      an equine foal loss.
AB  - Chlamydia psittaci is an important avian pathogen with spillover from infected
      wild and domesticated birds also posing a risk to human health. We recently
      reported a case of C. psittaci equine placentitis associated with further
      spillover to humans. Molecular typing of this case revealed it belonged to the
      6BC clade of C. psittaci, a globally distributed highly virulent set of strains,
      typically linked to infection spillover from parrots. Equine chlamydiosis
      associated with C. psittaci infection has previously been reported elsewhere in
      countries where parrots are not endemic, however, raising questions over the
      identity of infecting C. psittaci strains and the potential infection reservoirs.
      In this study, we describe the detection and molecular characterization of C.
      psittaci in a case of equine abortion in southern Queensland. Equine placenta and
      fresh liver and lung tissue from the necropsied foetus were positive by C.
      psittaci-specific qPCR. Chlamydia psittaci-specific multilocus sequence typing
      and ompA genotyping were used to further characterize the detected equine strains
      and an additional strain obtained from a dove from a different geographic region
      presenting with psittacosis. Molecular typing of this case revealed that the
      infecting equine strains were closely related to the C0sittaci detected in dove,
      all belonging to an evolutionary lineage of C. psittaci strains typically
      associated with infections of pigeons globally. This finding suggests a broader
      diversity of C. psittaci strains may be detected in horses and in association
      with reproductive loss, highlighting the need for an expansion of surveillance
      studies globally to understand the epidemiology of equine chlamydiosis and the
      associated zoonotic risk.

PMID- 29352511
TI  - Draft genome and reference transcriptomic resources for the urticating pine
      defoliator Thaumetopoea pityocampa (Lepidoptera: Notodontidae).
AB  - The pine processionary moth Thaumetopoea pityocampa (Lepidoptera: Notodontidae)
      is the main pine defoliator in the Mediterranean region. Its urticating larvae
      cause severe human and animal health concerns in the invaded areas. This species
      shows a high phenotypic variability for various traits, such as phenology,
      fecundity and tolerance to extreme temperatures. This study presents the
      construction and analysis of extensive genomic and transcriptomic resources,
      which are an obligate prerequisite to understand their underlying genetic
      architecture. Using a well-studied population from Portugal with peculiar
      phenological characteristics, the karyotype was first determined and a first
      draft genome of 537 Mb total length was assembled into 68,292 scaffolds (N50 =
      164 kb). From this genome assembly, 29,415 coding genes were predicted. To
      circumvent some limitations for fine-scale physical mapping of genomic regions of
      interest, a 3X coverage BAC library was also developed. In particular, 11 BACs
      from this library were individually sequenced to assess the assembly quality.
      Additionally, de novo transcriptomic resources were generated from various
      developmental stages sequenced with HiSeq and MiSeq Illumina technologies. The
      reads were de novo assembled into 62,376 and 63,175 transcripts, respectively.
      Then, a robust subset of the genome-predicted coding genes, the de novo
      transcriptome assemblies and previously published 454/Sanger data were clustered
      to obtain a high-quality and comprehensive reference transcriptome consisting of
      29,701 bona fide unigenes. These sequences covered 99% of the cegma and 88% of
      the busco highly conserved eukaryotic genes and 84% of the busco arthropod gene
      set. Moreover, 90% of these transcripts could be localized on the draft genome.
      The described information is available via a genome annotation portal
      (http://bipaa.genouest.org/sp/thaumetopoea_pityocampa/).

PMID- 29352512
TI  - TRPV1 antagonists that cause hypothermia, instead of hyperthermia, in rodents:
      Compounds' pharmacological profiles, in vivo targets, thermoeffectors recruited
      and implications for drug development.
AB  - AIM: Thermoregulatory side effects hinder the development of transient receptor
      potential vanilloid-1 (TRPV1) antagonists as new painkillers. While many
      antagonists cause hyperthermia, a well-studied effect, some cause hypothermia.
      The mechanisms of this hypothermia are unknown and were studied herein. METHODS:
      Two hypothermia-inducing TRPV1 antagonists, the newly synthesized A-1165901 and
      the known AMG7905, were used in physiological experiments in rats and mice. Their
      pharmacological profiles against rat TRPV1 were studied in vitro. RESULTS:
      Administered peripherally, A-1165901 caused hypothermia in rats by either
      triggering tail-skin vasodilation (at thermoneutrality) or inhibiting
      thermogenesis (in the cold). A-1165901-induced hypothermia did not occur in rats
      with desensitized (by an intraperitoneal dose of the TRPV1 agonist
      resiniferatoxin) sensory abdominal nerves. The hypothermic responses to A-1165901
      and AMG7905 (administered intragastrically or intraperitoneally) were absent in
      Trpv1-/- mice, even though both compounds evoked pronounced hypothermia in
      Trpv1+/+ mice. In vitro, both A-1165901 and AMG7905 potently potentiated TRPV1
      activation by protons, while potently blocking channel activation by capsaicin.
      CONCLUSION: TRPV1 antagonists cause hypothermia by an on-target action: on TRPV1
      channels on abdominal sensory nerves. These channels are tonically activated by
      protons and drive the reflectory inhibition of thermogenesis and tail-skin
      vasoconstriction. Those TRPV1 antagonists that cause hypothermia further inhibit
      these cold defences, thus decreasing body temperature. SIGNIFICANCE: TRPV1
      antagonists (of capsaicin activation) are highly unusual in that they can cause
      both hyper- and hypothermia by modulating the same mechanism. For drug
      development, this means that both side effects can be dealt with simultaneously,
      by minimizing these compounds' interference with TRPV1 activation by protons.

PMID- 29352514
TI  - An integrative review exploring the physical and psychological harm inherent in
      using restraint in mental health inpatient settings.
AB  - In Western society, policy and legislation seeks to minimize restrictive
      interventions, including physical restraint; yet research suggests the use of
      such practices continues to raise concerns. Whilst international agreement has
      sought to define physical restraint, diversity in the way in which countries use
      restraint remains disparate. Research to date has reported on statistics
      regarding restraint, how and why it is used, and staff and service user
      perspectives about its use. However, there is limited evidence directly exploring
      the physical and psychological harm restraint may cause to people being cared for
      within mental health inpatient settings. This study reports on an integrative
      review of the literature exploring available evidence regarding the physical and
      psychological impact of restraint. The review included both experimental and
      nonexperimental research papers, using Cooper's (1998) five-stage approach to
      synthesize the findings. Eight themes emerged: Trauma/retraumatization; Distress;
      Fear; Feeling ignored; Control; Power; Calm; and Dehumanizing conditions. In
      conclusion, whilst further research is required regarding the physical and
      psychological implications of physical restraint in mental health settings,
      mental health nurses are in a prime position to use their skills and knowledge to
      address the issues identified to eradicate the use of restraint and better meet
      the needs of those experiencing mental illness.

PMID- 29352513
TI  - Morbid obesity and type 2 diabetes alter intestinal fatty acid uptake and blood
      flow.
AB  - AIMS: Bariatric surgery is the most effective treatment to tackle morbid obesity
      and type 2 diabetes, but the mechanisms of action are still unclear. The
      objective of this study was to investigate the effects of bariatric surgery on
      intestinal fatty acid (FA) uptake and blood flow. MATERIALS AND METHODS: We
      recruited 27 morbidly obese subjects, of whom 10 had type 2 diabetes and 15 were
      healthy age-matched controls. Intestinal blood flow and fatty acid uptake from
      circulation were measured during fasting state using positron emission tomography
      (PET). Obese subjects were re-studied 6 months after bariatric surgery. The
      mucosal location of intestinal FA retention was verified in insulin resistant
      mice with autoradiography. RESULTS: Compared to lean subjects, morbidly obese
      subjects had higher duodenal and jejunal FA uptake (P < .001) but similar
      intestinal blood flow (NS). Within 6 months after bariatric surgery, obese
      subjects had lost 24% of their weight and 7/10 diabetic subjects were in
      remission. Jejunal FA uptake was further increased (P < .03). Conversely,
      bariatric surgery provoked a decrease in jejunal blood flow (P < .05) while
      duodenal blood flow was preserved. Animal studies showed that FAs were taken up
      into enterocytes, for the most part, but were also transferred, in part, into the
      lumen. CONCLUSIONS: In the obese, the small intestine actively takes up FAs from
      circulation and FA uptake remains higher than in controls post-operatively.
      Intestinal blood flow was not enhanced before or after bariatric surgery,
      suggesting that enhanced intestinal FA metabolism is not driven by intestinal
      perfusion.

PMID- 29352515
TI  - Principles of alemtuzumab immunoablation in hematopoietic cell transplantation
      for non-malignant diseases in children: A review.
AB  - Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly
      immunosuppressive with the ability to deplete T and B cells (in addition to other
      immune cell lines). A growing understanding of the PKs, dosing, and timing of
      administration of alemtuzumab has allowed for the study of its use as a
      conditioning agent for allogeneic HCT. The highly immunosuppressive properties of
      the drug are particularly appealing in the setting of non-malignant HCT, where
      GVHD provides no clinical benefit and relapse of malignancy is not applicable. In
      addition, the degree of immune suppression achieved with alemtuzumab has allowed
      for a reduction in the intensity of myeloablative cytotoxic agents included in
      some HCT conditioning regimens, allowing for fewer acute and late toxicities.
      This review paper will provide a comprehensive summary of the mechanism of
      action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in
      various allogeneic HCT protocols for non-malignant conditions and a summary of
      the data regarding its use for GVHD therapy. The goal of this review was to
      provide an understanding as to how alemtuzumab might be safely incorporated into
      HCT conditioning regimens for children with non-malignant disease, allowing for
      expanded access to curative HCT therapy.

PMID- 29352516
TI  - Successful hematopoietic cell transplantation following cardiac transplantation
      in two pediatric patients.
AB  - We report two patients who underwent cardiac transplantation at a young age and
      subsequently required a HCT for varied indications. Despite the challenges
      associated with HCT following cardiac transplant, including need for altered
      immunosuppression, toxicities related to chemotherapy exposure, and infection
      risks, both patients are currently alive and well. There is a paucity of such
      successful cases documented in the literature, and these cases highlight the
      critical importance of an experienced, multidisciplinary team when caring for
      this patient population.

PMID- 29352517
TI  - Micro-ribonucleic acid-binding site variants of type 2 diabetes candidate loci
      predispose to gestational diabetes mellitus in Chinese Han women.
AB  - AIMS/INTRODUCTION: Emerging evidence has suggested that the genetic background of
      gestational diabetes mellitus (GDM) was analogous to type 2 diabetes mellitus. In
      contrast to type 2 diabetes mellitus, the genetic studies for GDM were limited.
      Accordingly, the aim of the present study was to extensively explore the
      influence of micro-ribonucleic acid-binding single-nucleotide polymorphisms
      (SNPs) in type 2 diabetes mellitus candidate loci on GDM susceptibility in
      Chinese. MATERIALS AND METHODS: A total of 839 GDM patients and 900 controls were
      enrolled. Six micro-ribonucleic acid-binding SNPs were selected from 30 type 2
      diabetes mellitus susceptibility loci and genotyped using TaqMan allelic
      discrimination assays. RESULTS: The minor allele of three SNPs, PAX4 rs712699 (OR
      1.366, 95% confidence interval 1.021-1.828, P = 0.036), KCNB1 rs1051295 (OR
      1.579, 95% confidence interval 1.172-2.128, P = 0.003) and MFN2 rs1042842 (OR
      1.398, 95% confidence interval 1.050-1.862, P = 0.022) were identified to
      significantly confer higher a risk of GDM in the additive model. The association
      between rs1051295 and increased fasting plasma glucose (b = 0.006, P = 0.008), 3
      h oral glucose tolerance test plasma glucose (b = 0.058, P = 0.025) and
      homeostatic model assessment of insulin resistance (b = 0.065, P = 0.017) was
      also shown. Rs1042842 was correlated with higher 3-h oral glucose tolerance test
      plasma glucose (b = 0.056, P = 0.028). However, no significant correlation
      between the other included SNPs (LPIN1 rs1050800, VPS26A rs1802295 and NLRP3
      rs10802502) and GDM susceptibility were observed. CONCLUSIONS: The present
      findings showed that micro-ribonucleic acid-binding SNPs in type 2 diabetes
      mellitus candidate loci were also associated with GDM susceptibility, which
      further highlighted the similar genetic basis underlying GDM and type 2 diabetes
      mellitus.

PMID- 29352518
TI  - Ropivacaine preperitoneal wound infusion for pain relief and prevention of
      incisional hyperalgesia after laparoscopic colorectal surgery: a randomized,
      triple-arm, double-blind controlled evaluation vs intravenous lidocaine infusion,
      the CATCH study.
AB  - AIM: The abdominal incision for specimen extraction could trigger postoperative
      pain after laparoscopic colorectal resections (LCRs). Continuous wound infusion
      (CWI) of ropivacaine may be a valuable option for postoperative analgesia. This
      study was undertaken to evaluate the potential benefits of ropivacaine CWI on
      pain relief, metabolic stress reaction, prevention of wound hyperalgesia and
      residual incisional pain after LCR. A subgroup with intravenous lidocaine
      infusion (IVL) was added to discriminate between the peripheral and systemic
      effects of local anaesthetic infusions. METHOD: Patients were randomly allocated
      to three subgroups: CWI (0.2% ropivacaine 10 ml/h for 48 h); IVL (lidocaine 1.5%
      at 4 ml/h for 48 h); control group. RESULTS: In all, 95 patients were randomized
      (86 patients analysed). Postoperative pain intensity did not differ significantly
      between groups. Within the first 24 h after surgery, morphine requirement was
      significantly lower in the CWI group compared with the IVL group, but there was
      no significant difference compared with the control group (P = 0.02 and P = 0.15,
      respectively). The area of hyperalgesia did not differ significantly between
      subgroups, nor did the hyperalgesia ratio which was 1.2 cm (0.0-6.7) vs 1.9 cm
      (0.4-4.0) vs 2.0 cm (0.5-7.0) in the CWI, IVL and control groups respectively (P
      = 0.35). The number of patients reporting residual incisional pain after 3 months
      (3/26 vs 4/23 vs 4/23 in the CWI, IVL and control groups respectively) did not
      differ significantly between the groups, nor did their metabolic stress
      reactions. CONCLUSION: Ropivacaine CWI at the site of the abdominal incision did
      not provide any significant benefit either on analgesia or on the prevention of
      wound hyperalgesia after LCR.

PMID- 29352519
TI  - Nafamostat mesilate attenuates inflammation and apoptosis and promotes locomotor
      recovery after spinal cord injury.
AB  - AIM: Spinal cord injury (SCI) leads to severe neural damage for which there is
      currently no effective treatment. Exploration of the neuroprotective effect among
      clinically approved drugs will speed up clinical translation of SCI. Nafamostat
      mesilate (NM) as a synthetic serine protease inhibitor has been used clinically
      in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim
      of this study was to confirm the efficacy of NM in ameliorating SCI. METHODS:
      Intraperitoneal administration of NM was performed on a contusion SCI model in
      Wistar rat. Hematoxylin and eosin staining (H&E staining) and Luxol fast blue
      (LFB) staining were used to observe the histological lesions. Apoptosis was
      examined by TUNEL staining, Annexin V-FITC/PI, caspase-3, and Bcl-2. Cytokines
      and neurotrophins were tested by Western blot. Locomotion recovery assessed by
      hindlimb BBB score and the inclined plane test. RESULTS: Nafamostat mesilate
      treatment significantly improved locomotion recovery as assessed by hindlimb BBB
      scores and the inclined plane test. H&E staining and LFB staining showed a
      significant increase in spared tissue in both gray matter and white matter. NM
      decreased the expression of the proinflammatory cytokines TNF-alpha and IL-6. In
      addition, apoptosis was also significantly decreased, as shown by TUNEL staining
      and Annexin V-FITC/PI and by Western blotting for caspase-3 and Bcl-2 expression.
      Due to the mechanism of action of NM as a serine protease inhibitor, the drug
      decreased thrombin expression in the damaged spinal cord. Furthermore, NM
      increased the expression of neurotrophins (NT-3, BDNF, and NGF). CONCLUSIONS:
      Upon NM treatment, the functional and histological outcomes were improved, and
      microenvironment upon SCI was modulated. As a clinically approved drug, NM holds
      promise for clinical use after spinal cord injury.

PMID- 29352520
TI  - Ipragliflozin improves mitochondrial abnormalities in renal tubules induced by a
      high-fat diet.
AB  - AIMS/INTRODUCTION: Complete mechanisms of renoprotective effects of sodium
      glucose cotransporter 2 (SGLT2) inhibitors have not been elucidated yet.
      Mitochondrial biogenesis is regulated by membrane GTPases, such as optic atrophy
      factor 1 and mitofusion 2. Here, we investigated whether SGLT2 inhibition in mice
      fed with a high-fat diet (HFD) improved mitochondrial morphology and restored
      mitochondrial biogenesis-related molecules. MATERIALS AND METHODS: Mice were fed
      a control diet or HFD with or without ipragliflozin treatment. After 16 weeks,
      the kidneys were taken out and utilized for the analysis. RESULTS: HFD-fed mice
      treated with ipragliflozin showed increased caloric intake and ate more food than
      the control HFD-fed mice. Body and kidney weights, and blood glucose levels were
      not altered by ipragliflozin treatment in HFD-fed mice. Histological analysis
      showed that, compared with control mice, HFD-fed mice displayed tubular
      vacuolation, dilatation and epithelial cell detachment; ipragliflozin ameliorated
      these alterations. Furthermore, ultrastructural analysis showed that the tubule
      mitochondria of HFD-fed mice exhibited significant damage. Again, ipragliflozin
      reversed the damage to a normal state, and restored optic atrophy factor 1 and
      mitofusion 2 levels in HFD-fed mice. Increased urine 8-hydroxydeoxyguanosine
      levels in HFD-fed mice were suppressed by ipragliflozin as well. In vitro
      experiments using HK-2 cells revealed that either high glucose or high palmitate
      suppressed optic atrophy factor 1 and mitofusion 2 levels. Suppression of SGLT2
      by a specific small interfering ribonucleic acid or ipragliflozin restored these
      GTPase levels to their normal values. CONCLUSIONS: SGLT2 inhibition might act
      directly on tubular cells and protect kidney tubular cells from mitochondrial
      damage by metabolic insults regardless of blood glucose levels or improvement in
      bodyweight reduction.

PMID- 29352521
TI  - Microdenervation of the spermatic cord for post-vasectomy pain syndrome.
AB  - OBJECTIVE: To evaluate the outcomes of patients who underwent microdenervation of
      the spermatic cord (MDSC) for post-vasectomy pain syndrome (PVPS) at our
      institution. METHODS: A retrospective study of all patients who underwent MDSC
      for PVPS by a single surgeon between March 2002 and October 2016 was performed.
      Pain was documented using the numerical rating scale (NRS). Spermatic cord block
      (SCB) was performed on all patients, and success was defined as NRS score <=1 for
      >4 h. All patients had failed medical therapy prior to MDSC. All previous
      procedures for PVPS had been performed elsewhere. Surgical success was defined as
      a postoperative NRS score of <=1. RESULTS: A total of 27 patients with 28 scrotal
      units underwent MDSC for PVPS. The median (1st quartile; 3rd quartile) follow-up
      was 10 (2; 16.5) months. The median (range) duration of pain prior to surgery was
      57 (8-468) months. Pain was bilateral in 14 (52%), left-sided in eight (30%) and
      right-sided in five patients (19%). Data on SCB were available for 23 patients,
      with a success rate of 96%. The median (range) preoperative pain NRS score was 7
      (2-10). The median (range) pain score after SCB on the NRS scale was 0 (0-5). The
      median (range) postoperative pain score on the NRS was 0 (0-9). Overall success
      was achieved in 20 of 28 testicular units (71%). Patients with involvement of
      multiple structures in the scrotum (i.e. testis, epididymis, spermatic cord) had
      a success rate of 81% and were more likely to have a successful surgery (P <
      0.001). Five patients had failed a prior epididymectomy and three had failed a
      vaso-vasostomy for PVPS; this had no correlation with the success of MDSC (P =
      0.89). CONCLUSION: The MDSC procedure is a reasonably successful, durable and
      valuable approach for PVPS, especially when pain involves multiple structures in
      the scrotum (testis, epididymis, spermatic cord). MDSC was equally efficacious in
      patients who had previously failed a procedure for PVPS. No patient had a
      worsening NRS score after MDSC. This is the largest study to date evaluating MDSC
      for the treatment of PVPS.

PMID- 29352523
TI  - Unilateral incompatibility is linked to reduced pollen expression of a farnesyl
      pyrophosphate synthase.

PMID- 29352524
TI  - Effects of Physical Activity and Sedentary Behavior on Brain Response to High
      Calorie Food Cues in Young Adults.
AB  - OBJECTIVE: Physical activity (PA) promotes weight maintenance, potentially
      because of its beneficial effects on feeding behavior regulation via diminished
      food cue reactivity within brain reward regions. This study examined how levels
      of PA and sedentary behavior (SB) relate to brain responses to food cues.
      METHODS: Participants (22 lean, 18 with obesity) completed three to five PA
      recalls over 2 months. Average minutes per day of moderate to vigorous PA (MVPA)
      and SB were calculated. Participants completed a functional magnetic resonance
      imaging session, viewing food and nonfood images following glucose ingestion.
      Region of interest (ROI) analysis examined associations between MVPA and brain
      percent signal change in response to food versus nonfood images, controlling for
      obesity and sex. Secondary analysis examined associations between SB and brain
      responses to food cues. RESULTS: Greater MVPA was associated with decreased food
      cue reactivity after glucose across brain ROIs (beta = -0.00057, P = 0.005),
      controlling for obesity and sex. Greater SB was associated with increased food
      cue reactivity after glucose across brain ROIs in unadjusted analyses (beta =
      0.00041, P = 0.026). CONCLUSIONS: PA may have beneficial effects on brain
      regulation of feeding behavior after caloric intake in lean individuals and
      individuals with obesity.

PMID- 29352525
TI  - An MRM-Based Cytokeratin Marker Assay as a Tool for Cancer Studies: Application
      to Lung Cancer Pleural Effusions.
AB  - PURPOSE: The goal of this work was to develop an LC-MRM assay for the
      quantitative analysis of a set of established and diagnostically important
      cytokeratin (CK) markers used in cancer diagnosis, prognosis, and therapy
      monitoring. Second, the potential of this assay in lung cancer diagnosis through
      pleural effusion (PE) analysis was examined. EXPERIMENTAL DESIGN: A multiplexed
      MRM assay was developed for 17 CKs and their select caspase-cleaved fragments.
      Isotope-labeled standard peptides were used for high assay specificity and
      absolute peptide quantitation; with robust standard-flow LC coupled to a latest
      generation triple-quadrupole instrument for high sensitivity. The potential
      clinical applicability was demonstrated by the analysis of 118 PE samples.
      RESULTS: The MRM assay was evaluated for endogenous detection, linearity,
      precision, upper and lower limits of quantification, selectivity, reproducibility
      and peptide stability, and is generally applicable to any epithelial cancer
      study. A set of 118 patients with known pathologies allowed us to define the
      range of CK levels in clinical PE samples. Specific CKs were able to
      differentiate cancer-related PEs from those caused by benign ailments. In
      addition, they allowed to differentiate between PEs from subjects with small cell
      lung cancer versus non-small cell lung carcinoma, and to further differentiate
      the latter into its two subtypes, adenocarcinoma and squamous cell carcinoma.
      CONCLUSION AND CLINICAL RELEVANCE: An MRM-based CK assay for carcinoma studies
      can differentiate between the three lung cancer histological types using less
      invasive PE sampling providing potential therapy-guiding information on patients
      that are inoperable.

PMID- 29352527
TI  - Decline in suicide mortality after psychiatric hospitalization for depression in
      Finland between 1991 and 2014.

PMID- 29352526
TI  - ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a complex disease of the
      central nervous system. As new drugs are becoming available, knowledge on
      diagnosis and treatment must continuously evolve. There is therefore a need for a
      reference tool compiling current data on benefit and safety, to aid professionals
      in treatment decisions and use of resources across Europe. The European Committee
      of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European
      Academy of Neurology (EAN) have joined forces to meet this need. The objective
      was to develop an evidence-based clinical practice guideline for the
      pharmacological treatment of people with MS to guide healthcare professionals in
      the decision-making process. METHODS: This guideline has been developed using the
      GRADE methodology and following the recently updated EAN recommendations for
      guideline development. Clinical questions were formulated in PICO format
      (patient, intervention, comparator, outcome) and outcomes were prioritized
      according to their relevance to clinical practice. An exhaustive literature
      search up to December 2016 was performed for each question and the evidence is
      presented narratively and, when possible, combined in a meta-analysis using a
      random-effects model. The quality of evidence for each outcome was rated into
      four categories - very high, high, low and very low - according to the risk of
      bias. GRADE evidence profiles were created using GRADEprofiler (GRADEpro)
      software (Version 3.6). The recommendations with assigned strength (strong, weak)
      were formulated based on the quality of evidence and the risk-benefit balance.
      Consensus between the panellists was reached by use of the modified nominal group
      technique. RESULTS: A total of 10 questions have been agreed, encompassing
      treatment efficacy, response criteria, strategies to address suboptimal response
      and safety concerns and treatment strategies in MS and pregnancy. The guideline
      takes into account all disease-modifying drugs approved by the European Medicine
      Agency at the time of publication. A total of 20 recommendations were agreed by
      the guideline working group members after three rounds of consensus.

PMID- 29352528
TI  - WPA Scientific Sections activities in the triennium 2014-2017.

PMID- 29352530
TI  - Psychotherapies for depression in low- and middle-income countries: a meta
      analysis.
AB  - Most psychotherapies for depression have been developed in high-income Western
      countries of North America, Europe and Australia. A growing number of randomized
      trials have examined the effects of these treatments in non-Western countries. We
      conducted a meta-analysis of these studies to examine whether these
      psychotherapies are effective and to compare their effects between studies from
      Western and non-Western countries. We conducted systematic searches in
      bibliographical databases and included 253 randomized controlled trials, of which
      32 were conducted in non-Western countries. The effects of psychotherapies in non
      Western countries were large (g=1.10; 95% CI: 0.91-1.30), with high heterogeneity
      (I2 =90; 95% CI: 87-92). After adjustment for publication bias, the effect size
      dropped to g=0.73 (95% CI: 0.51-0.96). Subgroup analyses did not indicate that
      adaptation to the local situation was associated with the effect size.
      Comparisons with the studies in Western countries showed that the effects of the
      therapies were significantly larger in non-Western countries, also after
      adjusting for characteristics of the participants, the treatments and the
      studies. These larger effect sizes in non-Western countries may reflect true
      differences indicating that therapies are indeed more effective; or may be
      explained by the care-as-usual control conditions in non-Western countries, often
      indicating that no care was available; or may be the result of the relative low
      quality of many trials in the field. This study suggests that psychotherapies
      that were developed in Western countries may or may not be more effective in non
      Western countries, but they are probably no less effective and can therefore also
      be used in these latter countries.

PMID- 29352531
TI  - Bridging the dichotomy of actual versus aspirational digital health.

PMID- 29352529
TI  - Measuring and improving the quality of mental health care: a global perspective.
AB  - Mental disorders are common worldwide, yet the quality of care for these
      disorders has not increased to the same extent as that for physical conditions.
      In this paper, we present a framework for promoting quality measurement as a tool
      for improving quality of mental health care. We identify key barriers to this
      effort, including lack of standardized information technology-based data sources,
      limited scientific evidence for mental health quality measures, lack of provider
      training and support, and cultural barriers to integrating mental health care
      within general health environments. We describe several innovations that are
      underway worldwide which can mitigate these barriers. Based on these experiences,
      we offer several recommendations for improving quality of mental health care.
      Health care payers and providers will need a portfolio of validated measures of
      patient-centered outcomes across a spectrum of conditions. Common data elements
      will have to be developed and embedded within existing electronic health records
      and other information technology tools. Mental health outcomes will need to be
      assessed more routinely, and measurement-based care should become part of the
      overall culture of the mental health care system. Health care systems will need a
      valid way to stratify quality measures, in order to address potential gaps among
      subpopulations and identify groups in most need of quality improvement. Much more
      attention should be devoted to workforce training in and capacity for quality
      improvement. The field of mental health quality improvement is a team sport,
      requiring coordination across different providers, involvement of consumer
      advocates, and leveraging of resources and incentives from health care payers and
      systems.

PMID- 29352534
TI  - Increasing equity in access to mental health care: a critical first step in
      improving service quality.

PMID- 29352533
TI  - Complex PTSD and its correlates amongst female Yazidi victims of sexual slavery
      living in post-ISIS camps.

PMID- 29352535
TI  - Hikikomori: experience in Japan and international relevance.

PMID- 29352536
TI  - Schizotypy, schizotypic psychopathology and schizophrenia.

PMID- 29352532
TI  - The impact of severe mental disorders and psychotropic medications on sexual
      health and its implications for clinical management.
AB  - Sexual dysfunction often accompanies severe psychiatric illness and can be due to
      both the mental disorder itself and the use of psychotropic treatments. Many
      sexual symptoms resolve as the mental state improves, but treatment-related
      sexual adverse events tend to persist over time, and are unfortunately under
      recognized by clinicians and scarcely investigated in clinical trials. Treatment
      emergent sexual dysfunction adversely affects quality of life and may contribute
      to reduce treatment adherence. There are important differences between the
      various compounds in the incidence of adverse sexual effects, associated with
      differences in mechanisms of action. Antidepressants with a predominantly
      serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and
      mood stabilizers with hormonal effects are often linked to moderate or severe
      sexual dysfunction, including decreased libido, delayed orgasm, anorgasmia, and
      sexual arousal difficulties. Severe mental disorders can interfere with sexual
      function and satisfaction, while patients wish to preserve a previously
      satisfactory sexual activity. In many patients, a lack of intimate relationships
      and chronic deterioration in mental and physical health can be accompanied by
      either a poor sexual life or a more frequent risky sexual behaviour than in the
      general population. Here we describe the influence of psychosis and antipsychotic
      medications, of depression and antidepressant drugs, and of bipolar disorder and
      mood stabilizers on sexual health, and the optimal management of patients with
      severe psychiatric illness and sexual dysfunction.

PMID- 29352537
TI  - Chance of response to an antidepressant: what should we say to the patient?

PMID- 29352538
TI  - The promise and challenges of drug repurposing in psychiatry.

PMID- 29352541
TI  - Exploiting routine data for international benchmarking of quality in mental
      health care.

PMID- 29352539
TI  - Income inequality and depression: a systematic review and meta-analysis of the
      association and a scoping review of mechanisms.
AB  - Most countries have witnessed a dramatic increase of income inequality in the
      past three decades. This paper addresses the question of whether income
      inequality is associated with the population prevalence of depression and, if so,
      the potential mechanisms and pathways which may explain this association. Our
      systematic review included 26 studies, mostly from high-income countries. Nearly
      two-thirds of all studies and five out of six longitudinal studies reported a
      statistically significant positive relationship between income inequality and
      risk of depression; only one study reported a statistically significant negative
      relationship. Twelve studies were included in a meta-analysis with dichotomized
      inequality groupings. The pooled risk ratio was 1.19 (95% CI: 1.07-1.31),
      demonstrating greater risk of depression in populations with higher income
      inequality relative to populations with lower inequality. Multiple studies
      reported subgroup effects, including greater impacts of income inequality among
      women and low-income populations. We propose an ecological framework, with
      mechanisms operating at the national level (the neo-material hypothesis),
      neighbourhood level (the social capital and the social comparison hypotheses) and
      individual level (psychological stress and social defeat hypotheses) to explain
      this association. We conclude that policy makers should actively promote actions
      to reduce income inequality, such as progressive taxation policies and a basic
      universal income. Mental health professionals should champion such policies, as
      well as promote the delivery of interventions which target the pathways and
      proximal determinants, such as building life skills in adolescents and provision
      of psychological therapies and packages of care with demonstrated effectiveness
      for settings of poverty and high income inequality.

PMID- 29352542
TI  - Mental health of children living in war zones: a risk and protection perspective.

PMID- 29352543
TI  - A paradigm shift in psychiatric classification: the Hierarchical Taxonomy Of
      Psychopathology (HiTOP).

PMID- 29352540
TI  - Insight in schizophrenia spectrum disorders: relationship with behavior, mood and
      perceived quality of life, underlying causes and emerging treatments.
AB  - Poor insight in schizophrenia is prevalent across cultures and phases of illness.
      In this review, we examine the recent research on the relationship of insight
      with behavior, mood and perceived quality of life, on its complex roots, and on
      the effects of existing and emerging treatments. This research indicates that
      poor insight predicts poorer treatment adherence and therapeutic alliance, higher
      symptom severity and more impaired community function, while good insight
      predicts a higher frequency of depression and demoralization, especially when
      coupled with stigma and social disadvantage. This research also suggests that
      poor insight may arise in response to biological, experiential,
      neuropsychological, social-cognitive, metacognitive and socio-political factors.
      Studies of the effects of existing and developing treatments indicate that they
      may influence insight. In the context of earlier research and historical models,
      these findings support an integrative model of poor insight. This model suggests
      that insight requires the integration of information about changes in internal
      states, external circumstances, others' perspectives and life trajectory as well
      as the multifaceted consequences and causes of each of those changes. One
      implication is that treatments should, beyond providing education, seek to assist
      persons with schizophrenia to integrate the broad range of complex and
      potentially deeply painful experiences which are associated with mental illness
      into their own personally meaningful, coherent and adaptive picture.

PMID- 29352544
TI  - Improving quality of mental health care in low-resource settings: lessons from
      PRIME.

PMID- 29352545
TI  - WPA-WHO Africa Mental Health Forum - recommendations and position statement.

PMID- 29352546
TI  - Correction.

PMID- 29352547
TI  - The value of polygenic analyses in psychiatry.

PMID- 29352548
TI  - Prediction of psychosis across protocols and risk cohorts using automated
      language analysis.
AB  - Language and speech are the primary source of data for psychiatrists to diagnose
      and treat mental disorders. In psychosis, the very structure of language can be
      disturbed, including semantic coherence (e.g., derailment and tangentiality) and
      syntactic complexity (e.g., concreteness). Subtle disturbances in language are
      evident in schizophrenia even prior to first psychosis onset, during prodromal
      stages. Using computer-based natural language processing analyses, we previously
      showed that, among English-speaking clinical (e.g., ultra) high-risk youths,
      baseline reduction in semantic coherence (the flow of meaning in speech) and in
      syntactic complexity could predict subsequent psychosis onset with high accuracy.
      Herein, we aimed to cross-validate these automated linguistic analytic methods in
      a second larger risk cohort, also English-speaking, and to discriminate speech in
      psychosis from normal speech. We identified an automated machine-learning speech
      classifier - comprising decreased semantic coherence, greater variance in that
      coherence, and reduced usage of possessive pronouns - that had an 83% accuracy in
      predicting psychosis onset (intra-protocol), a cross-validated accuracy of 79% of
      psychosis onset prediction in the original risk cohort (cross-protocol), and a
      72% accuracy in discriminating the speech of recent-onset psychosis patients from
      that of healthy individuals. The classifier was highly correlated with previously
      identified manual linguistic predictors. Our findings support the utility and
      validity of automated natural language processing methods to characterize
      disturbances in semantics and syntax across stages of psychotic disorder. The
      next steps will be to apply these methods in larger risk cohorts to further test
      reproducibility, also in languages other than English, and identify sources of
      variability. This technology has the potential to improve prediction of psychosis
      outcome among at-risk youths and identify linguistic targets for remediation and
      preventive intervention. More broadly, automated linguistic analysis can be a
      powerful tool for diagnosis and treatment across neuropsychiatry.

PMID- 29352549
TI  - ICD-11 sessions in the 17th World Congress of Psychiatry.

PMID- 29352550
TI  - Improving the quality of global mental health care requires universal agreement
      on minimum national investment.

PMID- 29352551
TI  - Prevention of child maltreatment: strategic targeting of a curvilinear
      relationship between adversity and psychiatric impairment.

PMID- 29352552
TI  - "If you can't measure it, you can't manage it" - essential truth, or costly myth?

PMID- 29352553
TI  - Why measuring quality of mental health care is still an unmet challenge and how
      to meet it.

PMID- 29352554
TI  - Compulsive sexual behaviour disorder in the ICD-11.

PMID- 29352555
TI  - Mental health policies in Commonwealth countries.

PMID- 29352557
TI  - WPA scientific publications in the triennium 2014-2017.

PMID- 29352558
TI  - Order of operations in using expanded measurement to promote treatment quality
      improvement.

PMID- 29352559
TI  - Reward-related cognitive vulnerability to bipolar spectrum disorders.

PMID- 29352560
TI  - Mental health quality improvement goes global.

PMID- 29352556
TI  - What causes psychosis? An umbrella review of risk and protective factors.
AB  - Psychosis is a heterogeneous psychiatric condition for which a multitude of risk
      and protective factors have been suggested. This umbrella review aimed to
      classify the strength of evidence for the associations between each factor and
      psychotic disorders whilst controlling for several biases. The Web of Knowledge
      database was searched to identify systematic reviews and meta-analyses of
      observational studies which examined associations between socio-demographic,
      parental, perinatal, later factors or antecedents and psychotic disorders, and
      which included a comparison group of healthy controls, published from 1965 to
      January 31, 2017. The literature search and data extraction followed PRISMA and
      MOOSE guidelines. The association between each factor and ICD or DSM diagnoses of
      non-organic psychotic disorders was graded into convincing, highly suggestive,
      suggestive, weak, or non-significant according to a standardized classification
      based on: number of psychotic cases, random-effects p value, largest study 95%
      confidence interval, heterogeneity between studies, 95% prediction interval,
      small study effect, and excess significance bias. In order to assess evidence for
      temporality of association, we also conducted sensitivity analyses restricted to
      data from prospective studies. Fifty-five meta-analyses or systematic reviews
      were included in the umbrella review, corresponding to 683 individual studies and
      170 putative risk or protective factors for psychotic disorders. Only the ultra
      high-risk state for psychosis (odds ratio, OR=9.32, 95% CI: 4.91-17.72) and Black
      Caribbean ethnicity in England (OR=4.87, 95% CI: 3.96-6.00) showed convincing
      evidence of association. Six factors were highly suggestive (ethnic minority in
      low ethnic density area, second generation immigrants, trait anhedonia, premorbid
      IQ, minor physical anomalies, and olfactory identification ability), and nine
      were suggestive (urbanicity, ethnic minority in high ethnic density area, first
      generation immigrants, North-African immigrants in Europe, winter/spring season
      of birth in Northern hemisphere, childhood social withdrawal, childhood trauma,
      Toxoplasma gondii IgG, and non-right handedness). When only prospective studies
      were considered, the evidence was convincing for ultra-high-risk state and
      suggestive for urbanicity only. In summary, this umbrella review found several
      factors to be associated with psychotic disorders with different levels of
      evidence. These risk or protective factors represent a starting point for further
      etiopathological research and for the improvement of the prediction of psychosis.

PMID- 29352561
TI  - Psychosis-risk criteria in the general population: frequent misinterpretations
      and current evidence.

PMID- 29352563
TI  - Proper placement of colorectal self-expandable metal stents with the help of a
      thin colonoscope - a video vignette.

PMID- 29352562
TI  - CBS mutations are good predictors for B6-responsiveness: A study based on the
      analysis of 35 Brazilian Classical Homocystinuria patients.
AB  - BACKGROUND: Classical homocystinuria (HCU) is a monogenic disease caused by the
      deficient activity of cystathionine beta-synthase (CbetaS). The objective of this
      study was to identify the CBS mutations in Brazilian patients with HCU. METHODS:
      gDNA samples were obtained for 35 patients (30 families) with biochemically
      confirmed diagnosis of HCU. All exons and exon-intron boundaries of CBS gene were
      sequenced. Gene expression analysis by qRT-PCR was performed in six patients.
      Novel missense point mutations were expressed in E. coli by site-directed
      mutagenesis. RESULTS: Parental consanguinity was reported in 16 families, and
      pyridoxine responsiveness in five (15%) patients. Among individuals from the same
      family, all presented the same phenotype. Both pathogenic mutations were
      identified in 29/30 patients. Twenty-one different mutations were detected in
      nine exons and three introns; being six common mutations. Most prevalent were
      p.Ile278Thr (18.2%), p.Trp323Ter (11.3%), p.Thr191Met (11.3%), and c.828+1G>A
      (11.3%). Eight novel mutations were found [c.2T>C, c.209+1delG, c.284T>C,
      c.329A>T, c.444delG, c.864_868delGAG c.989_991delAGG, and c.1223+5G>T]. Enzyme
      activity in E. coli-expressed mutations was 1.5% for c.329A>T and 17.5% for
      c.284T>C. qRT-PCR analysis revealed reduced gene expression in all evaluated
      genotypes: [c.209+1delG; c.572C>T]; [c.2T>C; c.828+1G>A]; [c.828+1G>A;
      c.1126G>A]; [c.833T>C; c.989_991delAGG]; [c.1058C>T; c.146C>T]; and [c.444delG;
      c.444delG]. The expected phenotype according to the genotype (pyridoxine
      responsiveness) matched in all cases. CONCLUSIONS: Most patients studied were
      pyridoxine nonresponsive and presented early manifestations, suggesting severe
      phenotypes. Many private mutations were observed, but the four most prevalent
      mutations together accounted for over 50% of mutated alleles. A good genotype
      phenotype relationship was observed within families and for the four most common
      mutations.

PMID- 29352564
TI  - Optical metabolic imaging of irradiated rat heart exposed to ischemia-reperfusion
      injury.
AB  - Whole thoracic irradiation (WTI) is known to cause deterioration in cardiac
      function. Whether irradiation predisposes the heart to further ischemia and
      reperfusion (IR) injury is not well known. The aim of this study is to examine
      the susceptibility of rat hearts to IR injury following a single fraction of 15
      Gy WTI and to investigate the role of mitochondrial metabolism in the
      differential susceptibility to IR injury. After day 35 of irradiation, ex vivo
      hearts from irradiated and nonirradiated rats (controls) were exposed to 25-min
      global ischemia followed by 60-min IR, or hearts were perfused without IR for the
      same protocol duration [time controls (TC)]. Online fluorometry of metabolic
      indices [redox state: reduced nicotinamide adenine dinucleotide (NADH), oxidized
      flavin adenine dinucleotide (FAD), and NADH/FAD redox ratio] and functional
      variables [systolic left ventricular pressure (LVP), diastolic LVP (diaLVP),
      coronary flow (CF), and heart rate were recorded in the beating heart; developed
      LVP (dLVP) and rate pressure product (RPP)] were derived. At the end of each
      experimental protocol, hearts were immediately snap frozen in liquid N2 for later
      three-dimensional imaging of the mitochondrial redox state using optical
      cryoimaging. Irradiation caused a delay in recovery of dLVP and RPP after IR when
      compared to nonirradiated hearts but recovered to the same level at the end of
      reperfusion. CF in the irradiated hearts recovered better than the control hearts
      after IR injury. Both fluorometry and 3-D cryoimaging showed that in WTI and
      control hearts, the redox ratio increased during ischemia (reduced) and decreased
      on reperfusion (oxidized) when compared to their respective TCs; however, there
      was no significant difference in the redox state between WTI and controls. In
      conclusion, our results show that although irradiation of rat hearts compromised
      baseline cardiovascular function, it did not alter cardiac mitochondrial redox
      state and induce greater susceptibility of these hearts to IR injury.

PMID- 29352565
TI  - Quality of Life in Nonmelanoma Skin Cancer.

PMID- 29352566
TI  - In-Hospital Cerebrovascular Outcomes of Patients With Atrial Fibrillation and
      Cancer (from the National Inpatient Sample Database).
AB  - Limited data are available regarding the impact of cancer on cerebrovascular
      accidents in patients with atrial fibrillation (AF). We queried the Nationwide
      Inpatient Survey Database to identify patients who have diagnostic code for AF.
      We performed a 1:1 propensity matching based on the CHA2DS2VASc score and other
      risk factors between patients with AF who had lung, breast, colon, and esophageal
      cancer, and those who did not (control). The final cohort included a total of
      31,604 patients. The primary outcome of in-hospital cerebrovascular accidents
      (CVA) was lower in the cancer group than in the control group (4% vs 7%, p <
      0.001), but with only a weak association (f = -0.067). In-hospital mortality was
      higher in the cancer group than in the control group (18% vs 11%, p < 0.001; f = 
      0.099). A subgroup analysis according to cancer type showed similar results with
      a weak association with lower CVA in breast cancer (4% vs 7%; f = -0.066, p <
      0.001), lung cancer (4% vs 6%; f = -0.062, p < 0.001), colon cancer (4% vs 6%; f
      = -0.062, p < 0.001), and esophageal cancer (3% vs 7%; f = -0.095, p < 0.001)
      compared with the control groups. A weak association with higher in-hospital
      mortality was demonstrated in lung cancer (20% vs 11%; f = -0.127, p < 0.001),
      colon cancer (16% vs 11%; f = -0.076, p < 0.001), and esophageal cancer (20% vs
      12%; f = -0.111, p < 0.001) compared with the control groups, but no significant
      difference between breast cancer and control groups in mortality (11% vs 11%; f =
      -0.002, p = 0.888). In conclusion, in patients with AF, cancer diagnosis may not
      add a predictive role for in-hospital CVA beyond the CHADS2VASc score.

PMID- 29352567
TI  - Asymptomatic Ascending Aorta Aneurysm With Severe Aortic Regurgitation Caused by
      Multiple Intimal-Medial Tears Unassociated With Aortic Dissection.
AB  - A 62-year-old man was found to have an asymptomatic ascending aortic aneurysm
      (6.6 cm) associated with severe aortic regurgitation. Operative resection of the
      wall of the aneurysm disclosed its cause to be multiple healed intimal-medial
      tears without dissection involving a previously normal aorta. The concept of an
      intimal-medial tear unassociated with aortic dissection is a poorly recognized
      entity and these tears appear to be asymptomatic and after the aortic tearing
      lead to aneurysmal formation.

PMID- 29352568
TI  - Dual energy computed tomography should be a first line preoperative localization
      imaging test for primary hyperparathyroidism patients.
AB  - BACKGROUND: The objective of this study was to evaluate the performance of dual
      energy computed tomography (DECT) for preoperative parathyroid tumor (PT)
      localization in primary hyperparathyroid (PHP) patients. METHODS: A retrospective
      review was carried out of the medical records of all PHP patients who underwent
      ultrasound (US), Tc-99m sestamibi noncontrast single photon emission computed
      tomography (CT-MIBI), DECT and parathyroidectomy at a single center. RESULTS: The
      sensitivities and accuracies for preoperative PT localization in the 97 patient
      study population were: US 40% and 93%, CT-MIBI 64.0% and 97%, and DECT 84% and
      96%, respectively. In the one third of the study population that did not localize
      preoperatively with CT-MIBI and US, DECT correctly localized a PT in 21 cases
      (66%). DE-CT and US correctly localized a PT in 86% of cases, and only 5 (8%) of
      the cases that were accurately localized by a combination of CT-MIBI and US were
      not identified by DE-CT. CONCLUSIONS: DECT should be utilized as a first line
      preoperative PT localization study in PHP patients, and is also a sensitive
      salvage localization test.

PMID- 29352569
TI  - Patient navigation reduces time to care for patients with breast symptoms and
      abnormal screening mammograms.
AB  - INTRODUCTION: Concern has been raised about delays for patients presenting with
      breast symptoms in Canada. Our objective was to determine if our Rapid Access
      Breast Clinic (RABC) improved care for patients presenting with breast symptoms
      compared to the traditional system (TS). METHODS: A retrospective chart review
      tabulated demographic, surgical, pathology and radiologic information. Wait times
      to care were determined for patients presenting with symptomatic and screen
      detected breast problems. RESULTS: Time from presentation to surgeon evaluation
      was shorter in the RABC group for patients with breast symptoms (81 vs 35 days, p
      < .0001) and abnormal screens (72 vs 40 days, p = .092). Cancer patients with
      abnormal screens had shorter wait times than patients with breast symptoms in the
      TS (47 vs 70 days, p = .036). CONCLUSION: Coordination of imaging and clinical
      care reduces wait times in patients with both abnormal screening mammograms and
      symptomatic breast presentations and should be expanded in our province.

PMID- 29352570
TI  - The NLRP3 inflammasome and the emerging role of colchicine to inhibit
      atherosclerosis-associated inflammation.
AB  - Atherosclerosis is considered a chronic inflammatory disease of the arterial
      wall. Recently, compelling evidence has arisen for the role of monocytes and
      neutrophils and a particular protein complex that resides within these cells -
      the NLRP3 inflammasome - in atherosclerosis-associated inflammation. It is now
      also known that cholesterol crystals are present through all stages of
      atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory
      cells to produce interleukin 1beta and interleukin 18 - key mediators in the
      inflammatory cascade that drive plaque progression and instability. In this
      review, we describe the role of monocytes/macrophages and neutrophils in
      atherosclerosis, outline mechanisms of activation of the NLRP3 inflammasome in
      the setting of atherosclerosis-associated inflammation and discuss potential
      therapies that specifically target the NLRP3 inflammasome and/or its downstream
      mediators in atherosclerosis, with a particular focus on the emerging role of
      colchicine.

PMID- 29352571
TI  - A Significant Treatable Cause of Hearing Loss in Our Time.

PMID- 29352573
TI  - Hinfinity control for uncertain linear system over networks with Bernoulli data
      dropout and actuator saturation.
AB  - This paper investigates the Hinfinity control problems for uncertain linear
      system over networks with random communication data dropout and actuator
      saturation. The random data dropout process is modeled by a Bernoulli distributed
      white sequence with a known conditional probability distribution and the actuator
      saturation is confined in a convex hull by introducing a group of auxiliary
      matrices. By constructing a quadratic Lyapunov function, effective conditions for
      the state feedback-based Hinfinity controller and the observer-based Hinfinity
      controller are proposed in the form of non-convex matrix inequalities to take the
      random data dropout and actuator saturation into consideration simultaneously,
      and the problem of non-convex feasibility is solved by applying cone
      complementarity linearization (CCL) procedure. Finally, two simulation examples
      are given to demonstrate the effectiveness of the proposed new design techniques.

PMID- 29352572
TI  - Phase I combination study of the PARP inhibitor veliparib plus carboplatin and
      gemcitabine in patients with advanced ovarian cancer and other solid
      malignancies.
AB  - OBJECTIVE: Determine the maximum tolerated dose (MTD) and recommended phase II
      dose (RP2D) of veliparib combined with carboplatin and gemcitabine in patients
      with advanced ovarian cancer and other nonhematologic malignancies. METHODS: In
      this phase I study, patients with metastatic or unresectable solid tumors and <=2
      prior chemotherapy regimens received veliparib combined with carboplatin area
      under the curve (AUC) 4 on day 1 and gemcitabine 800mg/m2 on days 1 and 8 of a 21
      day cycle for maximum 10cycles, followed by optional veliparib maintenance
      therapy. Veliparib dosing commenced twice-daily (BID) continuously on day 1 of
      cycle 2; granulocyte colony-stimulating factor was permitted. Dose escalation
      used a Bayesian continual reassessment method. Safety, tolerability, and efficacy
      were evaluated. RESULTS: Seventy-five patients were enrolled (ovarian cancer,
      n=54; breast cancer, n=12). Thirty-six patients with ovarian cancer (67%) had
      known germline BRCA mutations. Most common treatment-related adverse events
      (TRAEs; >=60%) were thrombocytopenia, neutropenia, nausea, and anemia. Most
      common grade 3/4 TRAEs (>=40%) were neutropenia and thrombocytopenia. Dose
      limiting toxicities were thrombocytopenia and neutropenia. The MTD/RP2D was
      established at veliparib 250mg with carboplatin AUC 4 plus gemcitabine 800mg/m2.
      Responses were observed in 69% of patients with BRCA-deficient ovarian cancer
      (45% partial, 24% complete responses). Five patients remained on veliparib (80
      310mg BID) for >34cycles. CONCLUSIONS: Veliparib plus carboplatin/gemcitabine is
      tolerated, with a safety profile similar to carboplatin and gemcitabine alone.
      Combination therapy demonstrated promising preliminary antitumor activity in
      platinum-sensitive ovarian cancer patients with germline BRCA mutations. Trial
      registration ID: NCT01063816.

PMID- 29352574
TI  - Mismatch repair status as a beneficial predictor of fluorouracil-based adjuvant
      chemotherapy for pancreatic cancer.
AB  - BACKGROUND: Prior studies have indicated that patients with colorectal cancer
      with deficient mismatch repair have particular clinicopathologic features that
      distinguish them from patients with tumors with proficient mismatch repair.
      However, the effect of the mismatch repair status on outcomes after adjuvant
      chemotherapy for pancreatic cancer is still unknown. METHODS: Pancreatic cancer
      patients who underwent R0 resection between January 2013 and December 2015 at
      Fudan University Shanghai Cancer Center were included in this study. Mismatch
      repair status was determined by immunohistochemistry of mismatch repair proteins.
      Prognostic factors for deficient mismatch repair and proficient mismatch repair
      tumors were analyzed using Cox models. RESULTS: In total, 442 of 590 patients met
      the inclusion criteria, and their mismatch repair status was determined; the
      study group consisted of 75 patients with deficient mismatch repair and 367
      patients with proficient mismatch repair. Among the 147 patients who underwent
      surgery alone, patients with deficient mismatch repair tumors had a better
      overall survival than patients with proficient mismatch repair tumors (hazard
      ratio = 0.555 [95% confidence interval 0.331-0.931]; P = .026). Compared with
      patients who underwent surgery, 161 patients who received gemcitabine-based
      adjuvant chemotherapy had improvements in both disease-free survival and overall
      survival, regardless of mismatch repair status. However, 5-fluorouracil-based
      adjuvant chemotherapy yielded a favorable disease-free survival in the proficient
      mismatch repair group but conferred no survival advantage in the deficient
      mismatch repair group (hazard ratio = 0.930 [95% confidence interval 0.497
      1.743]; P = .821). CONCLUSION: Mismatch repair status in pancreatic cancer
      patients is not only a prognostic indicator but also a potential guiding factor
      for the use of 5-fluorouracil-based adjuvant chemotherapy.

PMID- 29352575
TI  - Double plication for spring-mediated intestinal lengthening of a defunctionalized
      Roux limb.
AB  - BACKGROUND: Spring-mediated distraction enterogenesis has been shown to increase
      the length of an intestinal segment. The goal of this study is to use suture
      plication to confine a spring within an intestinal segment while maintaining
      luminal patency to the rest of the intestine. METHODS: Juvenile mini-Yucatan pigs
      underwent placement of nitinol springs within a defunctionalized Roux limb of
      jejunum. A 20 French catheter was passed temporarily, and sutures were used to
      plicate the intestinal wall around the catheter at both ends of the encapsulated
      spring. Uncompressed springs placed in plicated segments and springs placed in
      nonplicated segments served as controls. The intestine was examined approximately
      3 weeks after spring placement. RESULTS: In the absence of plication, springs
      passed through the intestine within a week. Double plication allowed the spring
      to stay within the Roux limb for 3 weeks. Compared to uncompressed springs that
      showed no change in the length of plicated segments, compressed springs caused a
      significant 1.7-fold increase in the length of plicated segments. CONCLUSIONS:
      Intestinal plication is an effective method to confine endoluminal springs. The
      confined springs could lengthen intestine that maintains luminal patency. This
      approach may be useful to lengthen intestine in patients with short bowel
      syndrome. LEVEL OF EVIDENCE: Level I Experimental Study.

PMID- 29352576
TI  - Corrigendum to "Landscape determinants of spatio-temporal patterns of aerosol
      optical depth in the two most polluted metropolitans in the United States" [Sci.
      Total Environ. 609 (2017) 1556-1565].

PMID- 29352577
TI  - Erector spinae plane block for analgesia after lower segment caesarean section:
      Case report.
AB  - Effective postoperative analgesia after emergency caesarean section is important
      because it provides early recovery, ambulation and breast-feeding. The ultrasound
      guided erector spinae plane block has been orginally described for providing
      thoracic analgesia at the T5 transverse process by Forero et al. We performed
      post-operative bilateral erector spinae plane blocks with 20ml bupivacaine 0.25%
      at the level of the T9 transverse process in a pregnant woman after caesarean
      section. In this report, we described that bilateral erector spinae plane block
      at T9 level provides effective and long-lasting postoperative analgesia for lower
      abdominal surgery.

PMID- 29352578
TI  - A physiotherapist-led exercise and education program for preventing recurrence of
      low back pain: a randomised controlled pilot trial.
AB  - BACKGROUND: Before beginning a large and complex trial it is considered good
      practice to run a pilot study to assess the feasibility and acceptability so that
      quality is maintained and resources are not wasted. OBJECTIVE: To assesses the
      feasibility and acceptability of procedures for TOPS: Trial Of Prevention
      Strategies for low back pain. DESIGN: Randomised controlled pilot trial. METHODS:
      This is a trial of an 8 week, physiotherapist-led group exercise and education
      program for preventing recurrence of low back pain (LBP) in those recently
      recovered from LBP. We assessed the feasibility of recruitment and data
      collection procedures, acceptability of the trial interventions and loss-to
      follow up. RESULTS: The feasibility of recruitment, acceptability of the
      intervention and feasibility of physical activity data-collection procedures were
      all below anticipated levels. We enrolled 12 participants over 44 weeks, the
      adherence rate for the intervention group was 63% and valid physical activity
      data were obtained for 67% of the measurements. Follow-up methods for collection
      of LBP recurrence were successful with this information able to be collected for
      100% of participants. CONCLUSION: In response to the pilot, modifications were
      made to the main trial protocol. We will increase recruitment by relaxing
      inclusion criteria and expanding recruitment sites to include workplaces,
      community centres and via social media. We will facilitate compliance by
      expanding treatment sites to provide more options for participants to access the
      program and we will limit missing data by checking the validity of baseline
      physical activity measures prior to enrolment. TRIAL REGISTRATION: The study was
      prospectively registered with the Australian and New Zealand Clinical Trials
      Registry (ref: ACTRN12614000706673).

PMID- 29352579
TI  - Informed consent in physiotherapy practice: it is not what is said but how it is
      said.
AB  - This paper discusses the concept of informed consent in the context of
      contemporary biomedical ethics. A change in UK law regarding what information
      should be provided to patients has brought to the fore the role of
      physiotherapists in the process of gaining informed consent. It is important that
      physiotherapists are aware of how this change in the law will affect their
      practice. For an individual to consent, they need to have both the capacity and
      freedom to exercise rational thought. These concepts are challenged in
      contemporary biomedical ethics. An individual's ability to make rational
      decisions has been increasingly questioned by empirical evidence from behavioural
      psychology. In addition, the concept of freedom in contemporary neoliberal
      societies has also been critically examined. Liberal paternalism has been
      advocated by some as a means of helping patients to make better decisions about
      their care. Actualised as a 'nudge', liberal paternalism has been influential in
      a number of health policies, and has recently been discussed as a means of
      gaining consent from patients for assessments and treatments. Physiotherapists
      engage directly with patients and, through this engagement, construct a
      therapeutic environment that aims to build mutual trust. This paper questions the
      legitimacy of informed consent, and presents the argument that, through
      communicative actions, physiotherapists nudge patients into consenting to
      assessments and treatments.

PMID- 29352580
TI  - Individual student characteristics and attainment in pre registration
      physiotherapy: a retrospective multi site cohort study.
AB  - INTRODUCTION: Worldwide there is a desire to diversify the physiotherapy
      workforce. However, limited research indicates that some student characteristics
      linked to under-representation in pre registration physiotherapy education have
      lower attainment and greater attrition. This study explored the relationship
      between individual characteristics and success of students in pre registration
      physiotherapy education within South East England. DESIGN: A retrospective multi
      site cohort study including pre registration physiotherapy programmes in the
      South East of England. Anonymised data included background information (age,
      gender, ethnicity, socio-economic status) and outcomes (assessment marks, type of
      award and classification of degree). Analysis involved Bayesian regression models
      and ordinal logistic regression to examine the association of student
      characteristics on outcomes. RESULTS: Data from 1851 student records were
      collected from four institutions. There were significantly lower assessment
      scores for Asian (-11% 95% CI: -13.1 to -9.2), Black (-7%, 95% CI: -9.7 to -4.5)
      and Other/Mixed ethnicity groups (-5%, 95% CI: -7.1 to -2.4), most notable in
      clinical and observed assessments, compared to their White British colleagues.
      All BME groups also demonstrated worse odds for a one step lower overall award or
      no award (Black OR: 3.35, Asian OR: 3.97, Other OR: 2.03). Associations of
      learning disability, age and non-traditional entry routes with assessment scores
      and/or degree classification were also noted. CONCLUSION: These findings suggest
      significant attainment gaps in pre registration physiotherapy education in this
      specific geographical region, particularly for non-White ethnic and disability
      groups. The association with assessment type challenges educators to look beyond
      a purely student deficit model to explore all factors that may lead to
      inequality.

PMID- 29352581
TI  - Facile gas chromatography-tandem mass spectrometry stable isotope dilution method
      for the quantification of sesquiterpenes in grape.
AB  - Sesquiterpenes are a widespread class of compounds of increasing interest found
      in grapes and wines, amongst many other natural sources. Due to a lack of
      standards and the complexity of the mass spectra fragmentation, accurate
      quantification of these low concentration compounds had not previously been
      accomplished. The current paper presents a new method for the concurrent
      quantification of several sesquiterpenes. The multivariate method optimisation is
      presented. Synthesised isotopic standards were utilised in conjunction with solid
      phase microextraction (SPME) and gas chromatography-tandem mass spectrometry (GC
      MS/MS) to perform a standard isotope dilution assay (SIDA). The method was
      successfully applied to several grape must samples of four different cultivar. To
      the best of our knowledge this was the first time some of these sesquiterpenes
      were quantified in grape.

PMID- 29352582
TI  - A microfluidic distributor combining minimal volume, minimal dispersion and
      minimal sensitivity to clogging.
AB  - A new type of microfluidic flow distributor (referred to as the mixed mode or MM
      distributor) is proposed. Its performance characteristics are determined using
      computational fluid dynamics (CFD), both in the absence and the presence of
      clogging, which is an important problem in microfluidic systems. A comparison is
      made with two existing, well-performing distributor types: the bifurcating (BF)
      distributor and an optimized diverging distributor, the so-called radially
      interconnected (RI) distributor. It was found that, in the absence of clogging,
      the MM-distributor produces only a little more dispersion than the bifurcating
      (BF) distributor, but much less than the radially interconnected (RI)
      distributor. The dispersion in an MM-distributor also follows a similar
      dependency on its width (power ? 2) as the BF-distributor. The dispersion in the
      RI-distributor on the other hand displays a very disadvantageous 4th-order
      dependency on its width, prohibiting its use to distribute the flow across wide
      beds (order of millimeters or centimeters). These observations hold independently
      of the flow rate. With increasing degree of clogging, the MM-distributor rapidly
      becomes advantageous over the BF-distributor, owing to the fluid contact zones
      that are provided after each bifurcation step. This means that overall, and when
      the occurrence of clogging cannot be excluded, the MM-type distributor seems to
      offer the best possible compromise between the ability to cope with local
      clogging events and the dispersion in the absence of clogging.

PMID- 29352584
TI  - Discussion.

PMID- 29352583
TI  - Description and analysis of hospital pharmacies in Madagascar.
AB  - OBJECTIVE: Madagascar's health care system has operated without formal hospital
      pharmacies for more than two decades. The gradual integration of pharmacists in
      public hospitals since 2012 will allow the structuring of this field. This study
      was conducted to characterize the current situation regarding all aspects
      relating to the general functioning of hospital pharmacies and the services
      provided. METHODS: This qualitative research used semi-structured interviews.
      Interviewees' perceptions about the general organization and functioning of
      hospital pharmacies and details on services provided were collected. The 16
      interviewees were Ministry of Health staff members involved in hospital pharmacy,
      hospital directors, medical staff members and hospital pharmacy managers.
      Interviews were recorded, translated into French if conducted in Malagasy, and
      fully transcribed. Verbatim transcripts were coded according to the themes of
      hospital pharmacy and topical content analysis was performed. RESULTS: The
      principal issue perceived by interviewees was the heterogeneity of the system in
      terms of technical and financing management, with a main impact on the restocking
      of pharmaceutical products. The drug supply chain is not under control: no
      internal procedure has been established for the selection of pharmaceutical
      products, the quantification of needs is complex, stock management is difficult
      to supervise, a standard prescription protocol is lacking, dispensing is
      performed by unqualified staff, no pharmaceutical preparation is manufactured in
      the hospitals and administration occurs without pharmaceutical support.
      CONCLUSIONS: Progressive structuring of efficient hospital pharmacy services
      using the Basel statements for the future of hospital pharmacy is urgently needed
      to improve health care in Madagascar.

PMID- 29352585
TI  - Adjuvant chemotherapy improves survival in patients with completely resected T3N0
      non-small cell lung cancer invading the chest wall.
AB  - OBJECTIVE: Adjuvant chemotherapy prolongs survival in patients with non-small
      cell lung cancer with N1 disease or tumors larger than 4 cm. Patients with T3N0
      disease due to chest wall invasion often receive adjuvant chemotherapy because
      their disease is classified as stage II non-small cell lung cancer. This study
      evaluated whether chemotherapy improves survival after complete resection of T3N0
      non-small cell lung cancer with invasion of the chest wall. METHODS: Patients who
      underwent complete resection of N0 non-small cell lung cancer with invasion of
      the chest wall were identified in the National Cancer Database. We performed
      propensity matching of patients who received adjuvant chemotherapy and patients
      who did not and examined survival. RESULTS: We identified 2326 eligible patients;
      1050 patients (45%) received adjuvant chemotherapy, and 1276 patients (55%) did
      not. Patients who received chemotherapy after surgery had significantly better
      median survival than patients who did not (71 vs 39 months, P < .001). We
      identified 772 matched pairs. In the matched cohort, patients who received
      chemotherapy after surgery also had significantly better median survival (68 vs
      39 months without chemotherapy, P < .001). CONCLUSIONS: In this large database
      study, adjuvant chemotherapy significantly improved survival in patients with T3
      (chest wall) N0 non-small cell lung cancer after complete resection. Further
      studies are required to confirm our findings.

PMID- 29352587
TI  - Discussion.

PMID- 29352586
TI  - The impact of enhanced recovery after surgery (ERAS) protocol compliance on
      morbidity from resection for primary lung cancer.
AB  - OBJECTIVE: The adoption of Enhanced Recovery After Surgery programs in thoracic
      surgery is relatively recent with limited outcome data. This study aimed to
      determine the impact of an Enhanced Recovery After Surgery pathway on morbidity
      and length of stay in patients undergoing lung resection for primary lung cancer.
      METHODS: This prospective cohort study collected data on consecutive patients
      undergoing lung resection for primary lung cancer between April 2012 and June
      2014 at a regional referral center in the United Kingdom. All patients followed a
      standardized, 15-element Enhanced Recovery After Surgery protocol. Key data
      fields included protocol compliance with individual elements, pathophysiology,
      and operative factors. Thirty-day morbidity was taken as the primary outcome
      measure and classified a priori according to the Clavien-Dindo system. Logistic
      regression models were devised to identify independent risk factors for morbidity
      and length of stay. RESULTS: A total of 422 consecutive patients underwent lung
      resection over a 2-year period, of whom 302 (71.6%) underwent video-assisted
      thoracoscopic surgery. Lobectomy was performed in 297 patients (70.4%).
      Complications were experienced by 159 patients (37.6%). The median length of stay
      was 5 days (range, 1-67), and 6 patients (1.4%) died within 30 days of surgery.
      There was a significant inverse relationship between protocol compliance and
      morbidity after adjustment for confounding factors (odds ratio, 0.72; 95%
      confidence interval, 0.57-0.91; P < .01). Age, lobectomy or pneumonectomy, more
      than 1 resection, and delayed mobilization were independent predictors of
      morbidity. Age, lack of preoperative carbohydrate drinks, planned high dependency
      unit/intensive therapy unit admission, delayed mobilization, and open approach
      were independent predictors of delayed discharge (length of stay >5 days).
      CONCLUSIONS: Increased compliance with an Enhanced Recovery After Surgery pathway
      is associated with improved clinical outcomes after resection for primary lung
      cancer. Several elements, including early mobilization, appear to be more
      influential than others.

PMID- 29352588
TI  - Pulmonary reinterventions after complete unifocalization and repair in infants
      and young children with tetralogy of Fallot with major aortopulmonary
      collaterals.
AB  - BACKGROUND: Our institutional approach to tetralogy of Fallot (TOF) with major
      aortopulmonary collaterals (MAPCAs) emphasizes unifocalization and augmentation
      of the reconstructed pulmonary arterial (PA) circulation and complete
      intracardiac repair in infancy, usually in a single procedure. This approach
      yields a high rate of complete repair with excellent survival and low right
      ventricular (RV) pressure. However, little is known about remodeling of the
      unifocalized and reconstructed pulmonary circulation or about reinterventions on
      the reconstructed PAs or the RV outflow tract conduit. METHODS: We reviewed
      patients who underwent complete repair of TOF with MAPCAs at our center at <2
      years of age, either as a single-stage procedure or after previous procedures.
      Outcomes included freedom from conduit or PA intervention after repair, which
      were assessed by Cox regression and Kaplan-Meier analysis. RESULTS: The study
      cohort included 272 patients. There were 6 early deaths and a median of follow-up
      of 3.6 years after complete repair. Reinterventions on the pulmonary circulation
      were performed in 134 patients, including conduit interventions in 101 patients,
      branch PA interventions in 101, and closure of residual MAPCAs in 9. The first
      conduit reintervention consisted of surgical conduit replacement in 77 patients,
      transcatheter pulmonary valve replacement with a Melody valve in 14, and
      angioplasty or bare metal stenting in 10. Surgical PA reinterventions were
      performed in 46 patients and transcatheter reinterventions in 75 (both in 20).
      Most PA reinterventions involved a single lung, and most transcatheter
      reinterventions a single vessel. Freedom from conduit replacement or
      transcatheter pulmonary valve replacement was 70 +/- 3% at 5 years and was
      shorter in patients with smaller initial conduit size. Freedom from any PA
      reintervention was 64 +/- 3% at 5 years, with the greatest rate during the first
      year. On multivariable analysis, factors associated with longer freedom from any
      PA reintervention included lower postrepair RV:aortic pressure ratio and larger
      original conduit size. CONCLUSIONS: We were able to obtain follow-up data for the
      majority of patients, which demonstrated freedom from PA reintervention for two
      thirds of patients. The time course of and risk factors for conduit
      reintervention in this cohort appeared similar to previously reported findings in
      patients who received RV-PA conduits in early childhood for other anomalies.
      Relative to the severity of baseline pulmonary vascular anatomy in TOF with
      MAPCAs, reinterventions on the reconstructed PAs were uncommon after repair
      according to our approach, and major reinterventions were rare. Nevertheless, PA
      reinterventions are an important aspect of the overall management strategy.

PMID- 29352589
TI  - May the new suggested lower borderline limit of sweat chloride impact the
      diagnostic process for cystic fibrosis?

PMID- 29352590
TI  - Allergic Proctocolitis Is a Risk Factor for Functional Gastrointestinal Disorders
      in Children.
AB  - OBJECTIVE: To test the hypothesis that allergic proctocolitis, a cause of self
      limiting rectal bleeding in infants, can predispose to the development of
      functional gastrointestinal disorders (FGIDs) later in childhood. STUDY DESIGN:
      We studied a cohort of 80 consecutive patients diagnosed with allergic
      proctocolitis. Their sibling or matched children presenting to the same hospital
      for minor trauma served as controls. Parents of the patients with allergic
      proctocolitis and controls participated in a telephone interview every 12 months
      until the child was at least 4 years old. At that time, they were asked to
      complete the parental Questionnaire on Pediatric Gastrointestinal Symptoms, Rome
      III version. RESULTS: Sixteen of the 160 subjects (10.0%) included in the study
      met the Rome III criteria for FGIDs. Among the 80 patients with allergic
      proctocolitis, 12 (15.0%) reported FGIDs, compared with 4 of 80 (5.0%) controls
      (P = .035). After adjustment for age and sex, the OR for FGIDs in allergic
      proctocolitis group was 4.39 (95% CI, 1.03-18.68). FGIDs were significantly
      associated with iron deficiency anemia, duration of hematochezia, and younger age
      at presentation. In a multivariate analysis, only the duration of hematochezia
      was significantly associated with the development of FGIDs (OR, 3.14; 95% CI,1.72
      5.74). CONCLUSIONS: We have identified allergic proctocolitis as a new risk
      factor for the development of FGIDs in children. Our data suggest that not only
      infection, but also a transient early-life allergic inflammatory trigger may
      induce persistent digestive symptoms, supporting the existence of
      "postinflammatory" FGIDs.

PMID- 29352591
TI  - Potential Pitfalls in Applying Screening Criteria in Infants at Risk of Peanut
      Allergy.

PMID- 29352592
TI  - Development and validation of an ICD-10-based disability predictive index for
      patients admitted to hospitals with trauma.
AB  - BACKGROUND: There was no established disability predictive measurement for
      patients with trauma that could be used in administrative claims databases. The
      aim of the present study was to develop and validate a diagnosis-based disability
      predictive index for severe physical disability at discharge using the
      International Classification of Diseases, 10th revision (ICD-10) coding. METHODS:
      This retrospective observational study used the Diagnosis Procedure Combination
      database in Japan. Patients who were admitted to hospitals with trauma and
      discharged alive from 01 April 2010 to 31 March 2015 were included. Pediatric
      patients under 15 years old were excluded. Data for patients admitted to
      hospitals from 01 April 2010 to 31 March 2013 was used for development of a
      disability predictive index (derivation cohort), while data for patients admitted
      to hospitals from 01 April 2013 to 31 March 2015 was used for the internal
      validation (validation cohort). The outcome of interest was severe physical
      disability defined as the Barthel Index score of <60 at discharge. Trauma-related
      ICD-10 codes were categorized into 36 injury groups with reference to the
      categorization used in the Global Burden of Diseases study 2013. A multivariable
      logistic regression analysis was performed for the outcome using the injury
      groups and patient baseline characteristics including patient age, sex, and
      Charlson Comorbidity Index (CCI) score in the derivation cohort. A score
      corresponding to a regression coefficient was assigned to each injury group. The
      disability predictive index for each patient was defined as the sum of the
      scores. The predictive performance of the index was validated using the receiver
      operating characteristic curve analysis in the validation cohort. RESULTS: The
      derivation cohort included 1,475,158 patients, while the validation cohort
      included 939,659 patients. Of the 939,659 patients, 235,382 (25.0%) were
      discharged with severe physical disability. The c-statistics of the disability
      predictive index was 0.795 (95% confidence interval [CI] 0.794-0.795), while that
      of a model using the disability predictive index and patient baseline
      characteristics was 0.856 (95% CI 0.855-0.857). CONCLUSIONS: Severe physical
      disability at discharge may be well predicted with patient age, sex, CCI score,
      and the diagnosis-based disability predictive index in patients admitted to
      hospitals with trauma.

PMID- 29352594
TI  - Systematic review of uterine artery embolisation practice guidelines: are all the
      guidelines on the same page?
AB  - AIM: To evaluate the degree of concordance amongst the currently available
      guidelines informing the use of uterine artery embolisation (UAE), and identify
      any inconsistencies present. MATERIALS AND METHODS: Standards of practice and
      quality improvement guidelines were retrieved through a search of PubMed and
      EMBASE. Additional sets of guidelines were retrieved directly from the websites
      of known obstetrics and gynaecology and radiological associations. RESULTS:
      Eleven guidelines were retrieved from organisations located in Europe, North
      America, and Australia. Two main points of divergence were identified in the
      presented guidance: firstly, on whether submucosal, subserosal, and/or
      pedunculate fibroids should be considered a relative contraindication to UAE;
      secondly, on whether UAE should be recommended as an option in patients desiring
      future fertility. CONCLUSIONS: The guidelines reviewed generally suggest UAE to
      be a safe and effective option for fibroid treatment that can be offered as an
      alternative to surgical management; however, the number of differing
      interpretations arising from an apparently similar pool of evidence raises
      questions about the objectivity of practice guidelines. Although practice
      guidelines are understood to be a synthesis of clinical evidence and expert
      opinion, a systematic approach to presenting evidence is necessary to clearly
      distinguish empirically versus experientially informed guidance.

PMID- 29352593
TI  - Pre-admission proteinuria impacts risk of non-recovery after dialysis-requiring
      acute kidney injury.
AB  - Renal recovery after dialysis-requiring acute kidney injury (AKI-D) is an
      important clinical and patient-centered outcome. Here we examined whether the pre
      admission proteinuria level independently influences risk for non-recovery after
      AKI-D in a community-based population. All adult members of Kaiser Permanente
      Northern California who experienced AKI-D between January 1, 2009 and September
      30, 2015 were included. Pre-admission proteinuria levels were determined by
      dipstick up to four years before the AKI-D hospitalization and the outcome was
      renal recovery (survival and dialysis-independence four weeks and more) at 90
      days after initiation of renal replacement therapy. We used multivariable
      logistic regression to adjust for baseline estimated glomerular filtration rate
      (eGFR), age, sex, ethnicity, short-term predicted risk of death, comorbidities,
      and medication use. Among 5,347 adults with AKI-D, the mean age was 66 years, 59%
      were men, and 50% were white. Compared with negative/trace proteinuria, the
      adjusted odds ratios for non-recovery (continued dialysis-dependence or death)
      were 1.47 (95% confidence interval 1.19-1.82) for 1+ proteinuria and 1.92 (1.54
      2.38) for 2+ or more proteinuria. Among survivors, the crude probability of
      recovery ranged from 83% for negative/trace proteinuria with baseline eGFR over
      60 mL/min/1.73m2 to 25% for 2+ or more proteinuria with eGFR 15-29 mL/min/1.73m2.
      Thus, the pre-AKI-D level of proteinuria is a graded, independent risk factor for
      non-recovery and helps to improve short-term risk stratification for patients
      with AKI-D.

PMID- 29352595
TI  - Axillary tumour burden in women with one abnormal node on ultrasound compared to
      women with multiple abnormal nodes.
AB  - AIM: To determine if the number of abnormal nodes seen on preoperative axillary
      ultrasound (AUS) is a predictor of the number of positive nodes at histology for
      women with needle-biopsy-proven positive nodes. MATERIALS AND METHODS: This
      prospective multicentre cohort study included consecutive patients with early
      breast cancer who had needle-biopsy-proven positive nodes on AUS and underwent
      axillary lymph node dissection (ALND) between October 2015 and July 2016. The
      number of abnormal nodes at preoperative AUS was recorded by breast radiologists
      or radiographers. RESULTS: One hundred and twenty-three patients were included in
      the study. The median age of the women was 62 (range 30-93) years. Fifty-four of
      the 123 (44%) women had one abnormal node, whereas 69 (56%) had multiple abnormal
      nodes on AUS. Forty of the 123 (33%) women had two or fewer nodes with metastases
      at histology after ALND. Tumours <=20 mm (p<0.001) and one abnormal node on AUS
      (p<0.001) were associated with two or fewer nodes with metastases at ALND. Both
      remained significant in logistic regression analysis. The likelihood of at least
      three metastases based on the combination of these two factors had 95%
      sensitivity (79 of 83), 35% specificity (14 of 40), a negative predictive value
      of 78% (14 of 18), and a positive predictive value of 75% (79 of 105).
      CONCLUSION: Among women with needle-biopsy-proven positive nodes, around three in
      four women (78%) with an invasive tumour <=2 cm and one abnormal node on AUS have
      two or fewer positive nodes at ALND. These women are overtreated by upfront ALND
      and can be offered sentinel node biopsy (SNB).

PMID- 29352596
TI  - Thirty-day readmissions following parathyroidectomy: Evidence from the National
      Readmissions Database, 2013-2014.
AB  - PURPOSE: Parathyroidectomy is one of the most common procedures performed in the
      United States, and are increasingly being performed safely in the outpatient
      setting. However, complications from surgery can be life-threatening, and thus an
      understanding of who may be at risk is essential. We analyzed and compared the
      risk factors for patients readmitted within 30 days following inpatient
      parathyroidectomy for primary or secondary hyperparathyroidism. MATERIALS AND
      METHODS: We reviewed the National Readmissions Database from 2013 to 2014 for
      patients who received inpatient parathyroidectomy for primary or secondary
      hyperparathyroidism. The primary outcome was non-elective readmission within 30
      days. Multivariate logistic regression was used to analyze risk factor odds
      ratios for readmission. RESULTS: 7171 patients underwent inpatient
      parathyroidectomies in 2013 and 2014. 59.89% of parathyroidectomies were
      performed for primary hyperparathyroidism, with a 5.6% readmission rate. Most
      common causes of readmission were septicemia (13.69%), hypocalcemia (12.86%),
      heart failure (10.79%) and renal failure (9.54%). Having Medicare (OR: 1.71,
      CI:1.14-2.59, p = .01), Medicaid (OR: 3.24, CI: 2.03-5.17, p < .001), and self
      paying (OR: 2.43, CI: 1.11-5.32, p = .02), were associated with increased odds of
      readmission for those with primary hyperparathyroidism. 21.99% of
      parathyroidectomies were performed for secondary hyperparathyroidism, with a
      19.4% readmission rate. Most common causes of readmission were hypocalcemia
      (22.88%), hungry bone syndrome (14.38%), electrolyte disorders (13.73%), and
      renal failure (11.11%). CONCLUSION: Patients with secondary hyperparathyroidism
      are older, poorer and have more comorbidities than patients with primary
      hyperparathyroidism, and are more likely to be readmitted within 30 days of
      parathyroidectomy.

PMID- 29352598
TI  - WHO consultation on ETEC and Shigella burden of disease, Geneva, 6-7th April
      2017: Meeting report.
AB  - According to the 2015 Global Burden of Disease Study, diarrhea ranked ninth among
      causes of death for all ages, and fourth among children under 5 years old,
      accounting for an estimated 499,000 deaths in this young age group. It was also
      the second most common cause of years lived with disability (2.39 billion YLDs).
      The goal of the WHO/UNICEF Integrated Global Action Plan for the Prevention and
      Control of Pneumonia and Diarrhea (GAPPD) is to reduce deaths from diarrhea in
      children under 5 years of age to less than 1 per 1000 live births, by 2025.
      Development of new and improved vaccines against diarrheal infections is a
      fundamental element of the strategy towards achieving this goal. Enterotoxigenic
      Escherichia coli (ETEC) and Shigella are enteropathogens that cause significant
      global mortality and morbidity, particularly in low- and middle-income countries.
      In 2016, WHO's Product Development for Vaccines Advisory Committee (PDVAC)
      recommended that the WHO's Initiative for Vaccine Research (IVR) engage in this
      area, based on PDVAC's criteria of prioritizing the development of vaccines
      against pathogens that will address a major unmet public health need, and for
      which clinical candidates with a good probability of technical success are in the
      pipeline. As a first step, WHO's IVR convened global subject matter experts to
      discuss the current global ETEC and Shigella disease burden estimates, including
      the current understanding of the long-term indirect effects of ETEC and Shigella
      infection, and how these data may affect future decision making on vaccine
      development for both pathogens. The available global burden estimates for ETEC
      and Shigella differ with respect to the relative importance of these two
      pathogens. The mortality estimates vary between iterations published by the same
      group, as well as between estimates of different groups, although the uncertainty
      intervals are broad and overlapping. These variances are attributable to
      differences in the data available and incorporated in the models; the methods
      used to detect the pathogens; the modelling methodologies; and, to actual changes
      in the total number of diarrheal deaths over time. The changes in the most
      recently reported mortality estimates for these pathogens, as compared to
      previous iterations, has led to debate as to whether investment in development of
      stand-alone vaccines, rather than combined vaccines, is warranted from cost
      effectiveness and vaccine impact perspectives. Further work will be needed to
      understand better the variances and uncertainties in the reported mortality
      estimates to support investment decision making, and ultimately policy
      recommendations for vaccine use. In addition, a comprehensive assessment of the
      value proposition for vaccines against these pathogens is needed and will be
      strengthened if the long-term health consequences associated with diarrhea and
      dysentery due to these pathogens are better defined.

PMID- 29352599
TI  - [Detection of Chlamydia abortus in bovine reproductive losses in the province of
      La Pampa, Argentina].
AB  - Reproductive losses linked to an infectious etiology in bovine cattle are a major
      economic concern worldwide. In Argentina, more than 50% of abortion cases have
      unknown causes. Species belonging to Chlamydiaceae family are frequent etiologic
      agents of abortion around the world; however, there is yet no information on
      their prevalence in Argentina. The objective of this work was to identify
      Chlamydia spp., and particularly C. abortus in reproductive losses from bovine
      cattle in La Pampa, Argentina. Real time PCR targeting Chlamydiaceae-specific DNA
      fragments was performed on 251 samples obtained from bovine abortions and
      stillborns, and ArrayTube was used for species identification on positive
      samples. Chlamydiaceae DNA was detected in 12 samples of aborted fetuses (4.78%),
      83.33% (10/12) accounting for abortions and 16.66% (2/12) for stillborns. C.
      abortus was detected by ArrayTube in 5 cases (1.99% of all samples, and 41.67% of
      Chlamydiaceae positive samples). This study shows the first detection of
      Chlamydiaceae and C. abortus DNA on reproductive losses of bovine cattle in
      Argentina, and the described prevalence value (4.78%) should be taken as baseline
      value due to the type of samples analyzed. Detection of genetic material from
      Chlamydiaceae not matching any of the studied species could be due to
      intraspecies variants or local species not yet described. Further research on
      Chlamydia infections in bovine cattle in Argentina is imperative to describe
      their range, to analyze their economic and zoonotic implications and to make
      recommendations about prevention and control measures.

PMID- 29352600
TI  - Placental control of metabolic adaptations in the mother for an optimal pregnancy
      outcome. What goes wrong in gestational diabetes?
AB  - As pregnancy progresses the placental syncytiotrophoblast increasingly assumes
      control of maternal glucose homeostasis through the release and counter-balancing
      effects of placental lactogen (PL) and placental variant growth hormone (GH-V).
      While local actions of these hormones on placental growth and function are likely
      to exist, each also exerts indirect actions to ensure fetal nutritional
      availability through modulation of the maternal insulin/insulin-like growth
      factor axis. Peripheral insulin resistance results from the increasing levels of
      GH-V in the maternal circulation and is counter-balanced by an increase in
      insulin availability through an expansion of maternal pancreatic beta-cell mass.
      GH-V also increases maternal IGF-1 synthesis leading to enhanced placental growth
      and nutrient transporter activity. Maternal obesity and the presence of diabetes
      in pregnancy is associated with a disrupted balance in the placental expression
      of PL and GH-V. Several parallel mechanisms are likely to contribute to the
      increasing maternal beta-cell mass as gestation progresses, including a
      reactivation of beta-cell proliferation, an expansion of subsequent
      differentiation of resident beta-cell progenitors, and alpha-to beta-cell trans
      differentiation. Each of these pathways could potentially be modulated during
      pregnancy to increase beta-cell mass and prevent the onset of gestational
      diabetes.

PMID- 29352597
TI  - Potential drug targets in the Mycobacterium tuberculosis cytochrome P450 system.
AB  - The Mycobacterium tuberculosis genome encodes twenty cytochrome P450 enzymes,
      most or all of which appear to have specific physiological functions rather than
      being devoted to the removal of xenobiotics. However, in many cases their
      specific functions remain obscure. Considerable spectroscopic, biophysical,
      crystallographic, and catalytic information is available on nine of these
      cytochrome P450 enzymes, although gaps exist in our knowledge of even these
      enzymes. The available evidence indicates that at least three of the better
      characterized enzymes are promising targets for antituberculosis drug discovery.
      This review summarizes the information on the nine relatively well-characterized
      cytochrome P450 enzymes, with a particular emphasis on CYP121, CYP125, and CYP142
      from Mycobacterium tuberculosis and Mycobacterium smegmatis.

PMID- 29352601
TI  - Regulating needs: Exploring the role of insulin-like growth factor-2 signalling
      in materno-fetal resource allocation.
AB  - During pregnancy, the fetus requires nutrients supplied by the mother to grow and
      develop. However, the mother also requires sufficient resources to support the
      pregnancy, as well as, to maintain her health. Failure to regulate resource
      allocation between the mother and fetus can lead to pregnancy complications with
      immediate and life-long consequences for maternal and offspring health. This
      review explores the role of insulin-like growth factor (IGF)-2 in regulating
      materno-fetal resource allocation, particularly via its regulation of placental
      development and function.

PMID- 29352602
TI  - A Rare Cause of Pyogenic Flexor Tenosynovitis: Nocardia nova.
AB  - Infection complicates approximately 5% of open trigger digit releases. Both
      superficial and deep infections may occur. We present a unique case of a cactus
      farmer who underwent an uneventful thumb trigger finger release and subsequently
      developed pyogenic flexor tenosynovitis and acute carpal tunnel syndrome
      resulting from Nocardia nova infection.

PMID- 29352603
TI  - Increased Single-Nephron GFR in Normal Adults: Too Much of a Good Thing . . . or
      Maybe Not?

PMID- 29352604
TI  - A New Era of Renal Denervation Trials for Patients With Hypertension?

PMID- 29352605
TI  - A New Treatment Option for Highly Sensitized Patients Awaiting Kidney
      Transplantation.

PMID- 29352606
TI  - More From SPRINT (Systolic Blood Pressure Intervention Trial): A Closer Look at
      the Price of Intensive Blood Pressure Control.

PMID- 29352607
TI  - Integrated lung tissue mechanics one piece at a time: Computational modeling
      across the scales of biology.
AB  - The lung is a delicately balanced and highly integrated mechanical system. Lung
      tissue is continuously exposed to the environment via the air we breathe, making
      it susceptible to damage. As a consequence, respiratory diseases present a huge
      burden on society and their prevalence continues to rise. Emergent function is
      produced not only by the sum of the function of its individual components but
      also by the complex feedback and interactions occurring across the biological
      scales - from genes to proteins, cells, tissue and whole organ - and back again.
      Computational modeling provides the necessary framework for pulling apart and
      putting back together the pieces of the body and organ systems so that we can
      fully understand how they function in both health and disease. In this review, we
      discuss models of lung tissue mechanics spanning from the protein level (the
      extracellular matrix) through to the level of cells, tissue and whole organ, many
      of which have been developed in isolation. This is a vital step in the process
      but to understand the emergent behavior of the lung, we must work towards
      integrating these component parts and accounting for feedback across the scales,
      such as mechanotransduction. These interactions will be key to unlocking the
      mechanisms occurring in disease and in seeking new pharmacological targets and
      improving personalized healthcare.

PMID- 29352608
TI  - Differences in lung injury after IMRT or proton therapy assessed by 18FDG PET
      imaging.
AB  - BACKGROUND AND PURPOSE: To compare lung injury among non-small cell lung cancer
      (NSCLC) patients treated with IMRT or proton therapy as revealed by 18F-FDG post
      treatment uptake and to determine factors predictive for clinically symptomatic
      radiation pneumonitis. MATERIAL AND METHODS: For 83 patients treated with IMRT or
      proton therapy, planning CT and follow up 18F-FDG PET-CT were analyzed. Post
      treatment PET-CT was aligned with planning CT to establish a voxel-to-voxel
      correspondence between PET and planning dose images. 18F-FDG uptake as a function
      of radiation dose to normal lung was obtained for each patient. PET image-derived
      parameters as well as demographic, clinical, treatment and dosimetric patient
      characteristics were correlated with clinical symptoms of pneumonitis. RESULTS:
      The dose distributions for the two modalities were significantly different; V5
      was higher for IMRT, whereas V60 was higher for protons. The mean lung dose (MLD)
      was similar for the two modalities. The slope of linear 18F-FDG-uptake - dose
      response did not differ significantly between the two modalities. The MLD, slope,
      and 95th percentile of SUV were identified as three major factors associated with
      radiation pneumonitis. CONCLUSIONS: Despite significantly different dose
      distributions for IMRT and for protons, the slope of the SUV-dose linear
      regression line previously shown to be associated with RP did not differ between
      IMRT and protons. Patients who developed radiation pneumonitis had statistically
      significantly higher MLD and higher slope regardless of treatment modality.

PMID- 29352609
TI  - Induction of mitophagy in the HEI-OC1 auditory cell line and activation of the
      Atg12/LC3 pathway in the organ of Corti.
AB  - Autophagy is a highly evolutionary conserved quality control defense mechanism
      within cells, which has also been implicated in cell death processes. In the
      mammalian inner ear, autophagy has been shown to play a role during early
      morphogenesis as well as in adult cochlear hair cells exposed to ototoxic
      insults. Mitophagy, a selective autophagic cell process targeting mitochondria,
      hasn't been studied in the inner ear so far. On this work, we searched for
      molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1
      (HEI-OC1) cells as well as in the organ of Corti (OC). We first tested for the
      expression of Pink1/Park2 mRNA in 5-day-old C57BL/6 mice's cochleae using RT-PCR.
      We focused on the induction of mitophagy in HEI-OC1 cells as well as in the OC
      and investigated a possible mitophagic potential of the aminoglycoside agent
      gentamicin. The induction of mitophagy in HEI-OC1 cells was detected by
      objectivizing the translocation of fluorescence-tagged LC3 to mitochondria using
      confocal microscopy after a 6-h incubation with a well-described mitochondrial
      uncoupler and mitophagy-inducing agent: carbonyl cyanide m-chlorophenyl hydrazone
      (CCCP). Incubation with gentamicin generated no mitochondrial translocation of
      LC3. Protein levels of COXIV, Atg5/12 and LC3 were evaluated by an immunoblot
      analysis after a 24-h CCCP treatment as well as gentamicin. We demonstrated
      mitophagy after CCCP exposure in HEI-OC1 cells by showing a downregulation of
      COXIV. A downregulation of COXIV could also be visualized in the OC after CCCP. A
      significant oxygen consumption rate (OCR) changed in cells treated with CCCP as
      well as significant morphological changes of mitochondria by electron microscopy
      (EM) strengthen this assumption. Gentamicin exposure generated no impact on OCR
      or mitochondrial morphological changes by EM. Finally, we demonstrated changes in
      the expression of Atg12 and LC3 proteins in both the OC and HEI-OC1 cells after
      CCCP exposure but not after gentamicin. Our data indicate that gentamicin had no
      impact in the activation of mitophagy-neither in the HEI-OC1 cell line nor in the
      OC. Therefore, we speculate that mitophagic-independent mechanisms may underly
      aminoglycoside ototoxicity.

PMID- 29352610
TI  - Neural representation of octave illusion in the human cortex revealed with
      functional magnetic resonance imaging.
AB  - The auditory "octave illusion" arises when dichotic tones, presented one octave
      apart, alternate rapidly between the ears. This study aimed to explore the link
      between the perception of illusory pitches and brain activity during presentation
      of dichotic tones. We conducted a behavioral study of how participants perceived
      binaural dichotic tones of octave illusions and classified them, based on the
      reported percepts, in an illusion (ILL) group, without an illusion (non-ILL)
      group, and others. We recorded brain activity using functional magnetic resonance
      imaging and analyzed the activation due to dichotic illusion tones. The
      activation in the bilateral planum polare in the auditory cortex was
      significantly larger in the ILL group than in the non-ILL group. In the right
      premotor cortex, the non-ILL group showed a significantly larger activation than
      did the ILL group, suggesting that the sensation of the meter to the stimulus
      sound was significant in the non-ILL but not in the ILL group. The results
      indicated that the activity in these areas was related to the occurrence of
      octave illusions. The nonsignificant sensation of the meter to the stimulus sound
      in the ILL group may be consistent with the perception of octave illusion.

PMID- 29352611
TI  - High Blood Pressure Guidelines: Welcomed Advice, But Let's Not Lose the Patient
      Amid the Numbers.

PMID- 29352612
TI  - Biogeographical patterns of bacterial and archaeal communities from distant
      hypersaline environments.
AB  - Microorganisms are globally distributed but new evidence shows that the microbial
      structure of their communities can vary due to geographical location and
      environmental parameters. In this study, 50 samples including brines and
      sediments from Europe, Spanish-Atlantic and South America were analysed by
      applying the operational phylogenetic unit (OPU) approach in order to understand
      whether microbial community structures in hypersaline environments exhibited
      biogeographical patterns. The fine-tuned identification of approximately 1000
      OPUs (almost equivalent to "species") using multivariate analysis revealed
      regionally distinct taxa compositions. This segregation was more diffuse at the
      genus level and pointed to a phylogenetic and metabolic redundancy at the higher
      taxa level, where their different species acquired distinct advantages related to
      the regional physicochemical idiosyncrasies. The presence of previously
      undescribed groups was also shown in these environments, such as Parcubacteria,
      or members of Nanohaloarchaeota in anaerobic hypersaline sediments. Finally, an
      important OPU overlap was observed between anoxic sediments and their overlaying
      brines, indicating versatile metabolism for the pelagic organisms.

PMID- 29352614
TI  - WHO is in and WHO is out of the mouth, salivary glands, and jaws sections of the
      4th edition of the WHO classification of head and neck tumours.
AB  - This review of changes to the 4th edition of the WHO classification of head and
      neck tumours focuses on their impact on the surgical care of diseases that affect
      the salivary glands, jaws, and oral cavity. Updates to the chapter on the
      salivary glands include the addition of secretory carcinoma and sclerosing
      polycystic adenosis. The odontogenic cysts are back, and the odontogenic
      keratocyst is listed among them, as it has now lost its brief and confusing
      designation as a neoplasm. The newly-defined sclerosing odontogenic carcinoma and
      primordial odontogenic tumour have been added. Oropharyngeal tumours have been
      separated from those of the oral cavity, which reflects the importance of HPV in
      carcinoma of the tonsils. The problems of grading oral epithelial dysplasia
      persist.

PMID- 29352615
TI  - Gene Circuits for Dynamically Regulating Metabolism.
AB  - Gene circuits are a functional innovation in synthetic biology for engineering
      cellular behavior. Recent advances have demonstrated that gene circuits can be
      exploited for dynamically controlling pathway redirection and pathway balance to
      produce valuable chemicals. The next frontier is to engineer robust, sensitive,
      and efficient circuits that adapt to changing conditions.

PMID- 29352613
TI  - mRNA Translation Gone Awry: Translation Fidelity and Neurological Disease.
AB  - Errors during mRNA translation can lead to a reduction in the levels of
      functional proteins and an increase in deleterious molecules. Advances in next
      generation sequencing have led to the discovery of rare genetic disorders, many
      caused by mutations in genes encoding the mRNA translation machinery, as well as
      to a better understanding of translational dynamics through ribosome profiling.
      We discuss here multiple neurological disorders that are linked to errors in tRNA
      aminoacylation and ribosome decoding. We draw on studies from genetic models,
      including yeast and mice, to enhance our understanding of the translational
      defects observed in these diseases. Finally, we emphasize the importance of tRNA,
      their associated enzymes, and the inextricable link between accuracy and
      efficiency in the maintenance of translational fidelity.

PMID- 29352616
TI  - Assessing Advanced Airway Management Performance in a National Cohort of
      Emergency Medical Services Agencies.
AB  - STUDY OBJECTIVE: Although often the focus of quality improvement efforts,
      emergency medical services (EMS) advanced airway management performance has few
      national comparisons, nor are there many assessments with benchmarks accounting
      for differences in agency volume or patient mix. We seek to assess variations in
      advanced airway management and conventional intubation performance in a national
      cohort of EMS agencies. METHODS: We used EMS data from ESO Solutions, a national
      EMS electronic health record system. We identified EMS emergency responses with
      attempted advanced airway management (conventional intubation, rapid sequence
      intubation, sedation-assisted intubation, supraglottic airway insertion, and
      cricothyroidotomy). We also separately examined cases with initial conventional
      intubation. We determined EMS agency risk-standardized advanced airway management
      and initial conventional intubation success rates by using mixed-effects
      regression models, fitting agency as a random intercept, adjusting for patient
      age, sex, race, cardiac arrest, or trauma status, and use of rapid sequence or
      sedation-assisted intubation, and accounting for reliability variations from EMS
      agency airway volume. We assessed changes in agency advanced airway management
      and initial conventional intubation performance rank after risk and reliability
      adjustment. We also identified high and low performers (reliability-adjusted and
      risk-standardized success confidence intervals falling outside the mean).
      RESULTS: During 2011 to 2015, 550 EMS agencies performed 57,209 advanced airway
      management procedures. Among 401 EMS agencies with greater than or equal to 10
      advanced airway management procedures, there were a total of 56,636 procedures.
      Median reliability-adjusted and risk-standardized EMS agency advanced airway
      management success was 92.9% (interquartile range 90.1% to 94.8%; minimum 58.2%;
      maximum 99.0%). There were 56 advanced airway management low-performing and 38
      high-performing EMS agencies. Among 342 agencies with greater than or equal to 10
      initial conventional intubations, there were a total of 37,360 initial
      conventional intubations. Median reliability-adjusted and risk-standardized EMS
      agency initial conventional intubation success was 77.3% (interquartile range
      70.9% to 83.6%; minimum 47.1%; maximum 95.8%). There were 64 initial conventional
      intubation low-performing and 45 high-performing EMS agencies. CONCLUSION: In
      this national series, EMS advanced airway management and initial conventional
      intubation performance varied widely. Reliability adjustment and risk
      standardization may influence EMS airway management performance assessments.

PMID- 29352618
TI  - Point Shear Wave Elastography of the Spleen: Its Role in Patients with Portal
      Hypertension.
AB  - The goals of the study described here were to evaluate the feasibility and
      reproducibility of measuring spleen stiffness (SS) using point shear wave
      elastography in a series of cirrhotic patients and to investigate whether SS,
      liver stiffness (LS) and other non-invasive parameters are correlated with the
      presence of esophagogastric varices (EVs). Fifty-four cirrhotic patients with low
      grade EVs or without EVs at esophago-gastro-duodenoscopy were enrolled. They
      underwent abdominal ultrasound and Doppler ultrasound of hepatic vessels
      simultaneously with p-SWE of the liver and spleen. In 42 patients, the accuracy
      of LS and SS, as well as of platelet count and spleen longitudinal diameter, in
      predicting the presence of EVs was evaluated. The technical success was 90.74%
      for LS (49/54 patients) and 77.78% for SS (42/54 patients). Inter-observer
      agreement for SS measurement was high. Both LS and SS correlated with esophago
      gastro-duodenoscopy: LS had the highest accuracy in predicting the presence of
      EVs (area under the receiver operating characteristic curve [AUROC] = 0.913); SS
      had the lowest accuracy (AUROC = 0.675); platelet count and spleen diameter had
      intermediate accuracy (AUROC = 0.731 and 0.729, respectively). SS did not have an
      advantage over LS in predicting low-grade EVs and cannot be proposed as a useful
      tool in the diagnostic process of cirrhotic patients who require screening
      esophago-gastro-duodenoscopy.

PMID- 29352619
TI  - Quantitative Evaluation of Enzyme-Induced Porcine Articular Cartilage
      Degeneration Based on Observation of Entire Cartilage Layer Using Ultrasound.
AB  - Enzyme-induced articular cartilage degeneration resembling osteoarthritis was
      evaluated using a newly defined acoustic parameter, the "averaged magnitude
      ratio" (AMR), which has been suggested as an indicator of articular cartilage
      degeneration. In vitro experiments were conducted on porcine cartilage samples
      digested with trypsin for 2 h (n = 10) and 4 h (n = 13) and healthy control
      samples (n = 13). AMR was determined with 15- and 25-MHz ultrasound, and the
      integrated reflection coefficient (IRC) and apparent integrated backscattering
      coefficient (AIB) were also calculated for comparison. The Young's modulus of
      superficial cartilage was measured using atomic force microscopy. Performance of
      the AMR differs between 15 and 25 MHz, possibly because of frequency-related
      attenuation and resolution of ultrasound. At the proper settings, AMR exhibited a
      competence similar to that of IRC and AIB in detecting cartilage degeneration and
      could also detect differences in deeper positions. Furthermore, AMR has the
      advantages of being easy to measure and requiring no reference material.

PMID- 29352617
TI  - High frequency of C9orf72 hexanucleotide repeat expansion in amyotrophic lateral
      sclerosis patients from two founder populations sharing the same risk haplotype.
AB  - We characterized the C9orf72 hexanucleotide repeat expansion (RE) mutation in
      amyotrophic lateral sclerosis (ALS) patients of 2 distinct origins, Ashkenazi and
      North Africa Jews (AJ, NAJ), its frequency, and genotype-phenotype correlations.
      In AJ, 80% of familial ALS (fALS) and 11% of sporadic ALS carried the RE, a total
      of 12.9% of all AJ-ALS compared to 0.3% in AJ controls (odds ratio [OR] = 44.3, p
      < 0.0001). In NAJ, 10% of fALS and 9% of sporadic ALS carried the RE, a total of
      9.1% of all NAJ-ALS compared to 1% in controls (OR = 9.9, p = 0.0006). We
      identified a risk haplotype shared among all ALS patients, although an
      association with age at disease onset, fALS, and dementia were observed only in
      AJ. Variations were identified downstream the repeats. The risk haplotype and
      these polymorphisms were at high frequencies in alleles with 8 repeats or more,
      suggesting sequence instability. The different genotype-phenotype correlations
      and OR, together with the large range in age at onset, suggest that other
      modifiers and risk factors may affect penetrance and phenotype in ALS.

PMID- 29352620
TI  - Family caregivers' facilitation of daily adult prescription medication use.
AB  - OBJECTIVE: To describe ways family members assist adult patients with
      prescription medications at home, during medical visits and at the pharmacy.
      METHODS: Online survey of 400 adults (caregivers) who help another adult (care
      recipient) with prescription medication use. Regression modeled the contribution
      of caregiver communication during recipients' medical visits, evaluation of
      physicians' medication communication and discussions with the dispensing
      pharmacist on caregivers' assistance with home medication management. RESULTS:
      Female (68%) family members (94%) assisted care recipients with multimorbidity
      (mean 2.9 conditions) and polypharmacy (mean 3.2 prescriptions). On average,
      caregivers performed 3 visit communication behaviors (e.g., notetaking) and
      implemented 2.6 home medication management strategies (e.g., filling/monitoring
      pill boxes). Communication-related variables explained 17% of home medication
      management assistance; including caregivers' visit communication (std. beta
      0.31), physicians' medication communication (std. beta 0.15) and pharmacist
      discussions (std. beta 0.10). The final model included recipients' multimorbidity
      and caregiver education (std. betas 0.21 and 0.13) explaining 22% of caregiver
      assistance with home medication management. CONCLUSION: Caregivers' assistance
      with safe and effective home medication use crosses care contexts and is
      facilitated by clinician and pharmacist communication. PRACTICE IMPLICATIONS:
      Support for caregiver engagement in healthcare conversations can contribute to
      patient adherence and family-centered, high quality care.

PMID- 29352621
TI  - Associations between callous-unemotional traits and various types of involvement
      in school bullying among adolescents in Taiwan.
AB  - PURPOSE: This study examined associations between callous-unemotional (CU) traits
      and involvement in school bullying among 613 Taiwanese adolescents. METHODS: CU
      traits were determined using the self-reported Chinese versions of the Inventory
      of Callous and Unemotional Traits (C-ICUT) and the School Bullying Experience
      Questionnaire (C-SBEQ). The study used logistic regression analysis to assess
      associations between CU traits and types of involvement in school bullying, with
      controls for the effect of age, sex, and residential background. RESULTS: Higher
      levels of the callous trait were positively associated with greater risk of being
      a victim of physical bullying and belongings snatch, or a perpetrator of verbal,
      relational and physical bullying and belongings snatch. Higher levels of the
      unemotional trait were positively associated with greater risk of being a victim
      of verbal and relational bullying. The uncaring trait had no significant
      associations with any type of bullying involvement. CONCLUSION: The role played
      by CU traits should, therefore, be examined when developing programs to detect
      and prevent school bullying.

PMID- 29352622
TI  - Anaesthesia for Caesarean section in a patient with Parkinson's disease.
AB  - Parkinson's disease is prevalent worldwide but mainly affects the elderly and is
      rarely seen in women of child-bearing age. The clinical signs and symptoms, the
      physiological changes of pregnancy, and drug interactions, pose unique challenges
      for the anaesthetic management of patients with Parkinson's disease who present
      for delivery. A 36-year-old primigravid woman at 36 weeks' gestation, with
      Parkinson's disease, presented for pre-anaesthesia assessment prior to elective
      caesarean section. Her Parkinson's disease had been diagnosed four years
      previously and was treated with Sinemet (levodopa/carbidopa) and pramipexole.
      Despite maximum allowable drug doses in pregnancy, she reported disease
      progression, with right-sided weakness in the upper and lower limbs and an
      altered gait. Spinal anaesthesia for elective Caesarean section was performed in
      the sitting position, using 0.5% hyperbaric bupivacaine, morphine 150 ug and
      fentanyl 25 ug. The anaesthesia and Caesarean section were uneventful. She was
      discharged home with a healthy baby on the fourth postoperative day.

PMID- 29352623
TI  - Effect of method of anesthesia on the reproductive and obstetric outcomes of
      heterotopic pregnancies.
AB  - BACKGROUND: Anesthesia is commonly used for surgical termination of the
      extrauterine component of heterotopic pregnancy. We sought to evaluate the
      effects of general and regional anesthesia during salpingectomy on reproductive
      and obstetric outcomes of heterotopic pregnancies. METHODS: A two-center,
      retrospective cohort study was conducted, and 49 heterotopic pregnancies were
      included. Baseline characteristics, reproductive and obstetric outcomes were
      compared between the general anesthesia and regional anesthesia groups. RESULTS:
      Baseline characteristics were comparable for age, weeks of gestation at
      diagnosis, and duration of anesthesia. No significant difference was found in
      pregnancy outcome, perinatal outcome or neonatal weight (P >0.05). The rate of
      miscarriage in the general anesthesia group was 23.5% versus the regional
      anesthesia group 15.6% (P >0.05). CONCLUSION: With respect to reproductive and
      obstetric outcomes, this retrospective study found no difference between general
      anesthesia and regional anesthesia used for early heterotopic pregnancy.

PMID- 29352624
TI  - Anesthetic management of two parturients with cerebral palsy and prior selective
      dorsal rhizotomy.
AB  - Selective dorsal rhizotomy is a surgical spine procedure used to reduce
      spasticity in patients with upper motor neuron dysfunction caused by conditions
      such as cerebral palsy. The optimal anesthetic approach for obstetric patients
      who have undergone a selective dorsal rhizotomy is unknown. The use and efficacy
      of neuraxial anesthesia in these patients has not been described. We describe the
      use of neuraxial anesthesia in two patients with prior selective dorsal
      rhizotomy. Unless contraindicated for other reasons, a neuraxial anesthetic
      approach appears to be an effective option in patients with a history of a
      selective dorsal rhizotomy.

PMID- 29352625
TI  - Unilateral repetitive tibial nerve stimulation improves neurogenic claudication
      and bilateral F-wave conduction in central lumbar spinal stenosis.
AB  - BACKGROUND: Repetitive electrical nerve stimulation of the lower limb may improve
      neurogenic claudication in patients with lumbar spinal stenosis (LSS) as
      originally described by Tamaki et al. We tested if this neuromodulation technique
      affects the F-wave conduction on both sides to explore the underlying physiologic
      mechanisms. METHODS: We studied a total of 26 LSS patients, assigning 16 to a
      study group receiving repetitive tibial nerve stimulation at the ankle (RTNS) on
      one leg, and 10 to a group without RTNS. RTNS conditioning consisted of a 0.3-ms
      duration square-wave pulse with an intensity 20% above the motor threshold,
      delivered at a rate of 5 Hz for 5 min. All patients underwent the walking test
      and the F-wave and M-wave studies for the tibial nerve on both sides twice; once
      as the baseline, and once after either the 5-min RTNS or 5-min rest. RESULTS:
      Compared to the baselines, a 5-min RTNS increased claudication distance (176 +/-
      96 m vs 329 +/- 133 m; p = 0.0004) and slightly but significantly shortened F
      wave minimal onset latency (i.e., increased F-wave conduction velocity) not only
      on the side receiving RTNS (50.7 +/- 4.0 ms vs 49.2 +/- 4.2 ms; p = 0.00081) but
      also on the contralateral side (50.1 +/- 4.6 ms vs 47.9 +/- 4.2 ms; p = 0.011). A
      5-min rest in the group not receiving RTNS neither had a significant change on
      claudication distance nor on any F-wave measurements. The M response remained
      unchanged in both groups. CONCLUSIONS: The present study verified a beneficial
      effect of unilaterally applied RTNS of a mild intensity on neurogenic
      claudication and bilateral F-wave conduction. Our F-wave data suggest that this
      type of neuromodulation could be best explained by an RTNS-induced widespread
      sympathetic tone reduction with vasodilation, which partially counters a walking
      induced further decline in nerve blood flow in LSS patients who already have
      ischemic cauda equina.

PMID- 29352626
TI  - Differences between sexes in the standard and advanced dimensioning of lateral
      meniscal allografts.
AB  - BACKGROUND: There are many different methods of meniscal allograft measurements,
      which depend on individual tissue bank procedures. Due to the lack of a
      standardised method of dimensioning, measurement results may vary between
      individual cases. Consequently, allograft may be mismatched to the patient's knee
      anatomy. The purpose of this study was to measure four meniscal dimensions - two
      standard and two specific - and then compare them between sexes. METHODS:
      Fourteen cadaveric lateral menisci (seven male and seven female) were scanned
      using a microtomography scanner. The obtained three-dimensional (3-D) models of
      each meniscus were analysed, taking into account four dimensions: circumference,
      width, central meniscal concavity, and total meniscal volume. The computer
      researcher was not informed of the original data of the meniscal samples until
      the calculations were completed. RESULTS: No statistical between-sex differences
      were found in the standard dimensions. The specific dimensions, in turn,
      presented statistically significant between-sex differences (P>0.05). The mean
      difference between male and female total volume of the meniscus was equal to
      36.59%, and the mean difference between male and female central meniscal
      concavity surface was equal to 31.22%. CONCLUSION: This study found that sex
      should be taken into account as an important factor during a matching procedure
      performed by tissue bank staff.

PMID- 29352627
TI  - Indications and limits of stereoelectroencephalography (SEEG).
AB  - Epilepsy surgery is now an accepted treatment to achieve seizure control in
      carefully selected patients, both children and adults, suffering from drug
      resistant focal epilepsy. Although surgical strategies can often be defined on
      the basis of non-invasive diagnostic procedures, and despite the recent advances
      in this field, an increasing number of more complex cases requires invasive EEG
      (iEEG) to provide precise information on the localization of the epileptogenic
      zone (EZ), its relationships with eloquent cortex (EC), and the feasibility of a
      tailored surgical resection. Stereoelectroencephalography (SEEG) is one of the
      iEEG techniques currently used in the presurgical work-up, and it is well
      distinguished from other invasive techniques, such as subdural grids and strips.
      SEEG depth electrodes enable exploration of deeply located structures and
      lesions, and of buried cortex, which are not easily assessable by subdural or
      other iEEG methods. Simultaneous recording of SEEG signals from deep and
      superficial brain structures allows, when the position of each electrode is
      precisely determined, delineation of a three-dimensional, spatial and temporal
      organization of epileptic activities. In the following chapter we discuss some
      specific indications (temporal or extra-temporal, lesional or non-lesional
      epilepsies) as well as the limits of the SEEG technique, with respect to some
      epileptological issues during presurgical evaluation.

PMID- 29352628
TI  - Non-invasive mechanical ventilation in myotonic dystrophy type 1? Hypoventilation
      versus quality of life perspective.

PMID- 29352629
TI  - An in silico comparative dosimetric study of postmastectomy locoregional
      irradiation using intensity-modulated vs 3-dimensional conventional radiotherapy.
AB  - An in silico dosimetric evaluation of intensity-modulated radiation therapy
      (IMRT) vs 3-dimensional conventional radiation therapy (3D-CRT) treatment plans
      in postmastectomy radiation therapy (PMRT) to the chest wall and regional
      lymphatics was conducted. Twenty-five consecutive patients with breast cancer
      referred for locoregional PMRT, stages T2-4 with N1-3, were planned to receive 50
      Gy in 25 fractions with IMRT. Additionally, a 3D-CRT plan was generated using
      identical contours for the clinical target volumes (CTV), planning target volumes
      (PTV), and organs at risk (OAR). Treatment plans were assessed using dose-volume
      histogram (DVH) parameters of D98, D95, D50, D2, and homogeneity index for
      individual CTVs and PTVs. OARs evaluated were ipsilateral and contralateral
      lungs, heart, spinal cord, and opposite breast. Most DVH parameters pertaining to
      CTVs and PTVs significantly favored IMRT. V20 for ipsilateral and contralateral
      lungs, D33 of heart and maximum dose to spinal cord favored IMRT (all p < 0.001).
      The mean dose to the opposite breast was significantly lesser with 3D-CRT (5.8 +/
      1.8 Gy vs 2.0 +/- 1.0 Gy, p < 0.001). Thus, except for the mean dose to the
      opposite breast, the compliance to DVH constraints applied to PTV and OARs were
      significantly better with IMRT. At a median follow-up of 76 months (7-91), none
      had locoregional failure or pulmonary or cardiac morbidity. For PMRT, requiring
      comprehensive irradiation to both chest wall and regional lymphatics, IMRT offers
      superior dosimetric advantages over 3D-CRT. This was also corroborated by long
      term outcomes in these patients treated with IMRT.

PMID- 29352630
TI  - Surgical damage to the lymphatic system promotes tumor growth via impaired
      adaptive immune response.
AB  - BACKGROUND: Both lymph nodes (LNs) and lymphatic channels from primary sites to
      regional LNs are critical for initiation of adaptive immunity. However, as LNs
      are common metastatic sites in skin cancers, LN biopsies or dissections are
      frequently performed. In addition, reconstructive skin flaps after tumor
      resection may damage lymphatic flow from primary sites to regional LNs.
      OBJECTIVE: This study was designed to investigate the effect on tumor progression
      by such surgeries. METHODS: We developed a mouse model that simulates LNs
      dissection or skin flap that blocks lymphatic flow from primary sites to regional
      LNs and monitored tumor progression. RESULTS: As a poor immunogenic tumor line,
      the growth of inoculated B16F10 melanoma into syngeneic C57BL/6 mice was not
      affected by these surgeries. However, the growth of the same cell line in
      allogenic Balb/c mice was accelerated while immune cell infiltration (CD4+ and
      CD8+ T cells) into the tumor was reduced by these surgeries. In addition, both
      cytotoxicity against B16F10 melanoma and numbers of apoptotic tumor cells were
      diminished by these surgeries. Similarly, tumor growth of the immunogenic MC38
      cell line in syngeneic C57BL/6 mice was accelerated and immune cell infiltration
      and apoptotic tumor cells were reduced by these surgeries. CONCLUSION: These
      results strongly indicate that surgical damage of the lymphatic system may
      promote tumor progression via impaired adaptive immune response.

PMID- 29352631
TI  - We could learn much more from 1918 pandemic-the (mis)fortune of research relying
      on original death certificates.
AB  - PURPOSE: The analysis of historical death certificates has enormous potential for
      understanding how the health of populations was shaped by diseases and epidemics
      and by the implementation of specific interventions. In Brazil, the systematic
      archiving of mortality records was initiated only in 1944-hence the analysis of
      death registers before this time requires searching for these documents in public
      archives, notaries, parishes, and especially ancient cemeteries, which are often
      the only remaining source of information about these deaths. This article
      describes an effort to locate original death certificates in Brazil and document
      their organization, accessibility, and preservation. METHODS: To this end, we
      conducted an exploratory study in 19 of the 27 Brazilian states, focusing on the
      period surrounding the 1918 influenza pandemic (1913-1921). We included 55
      cemeteries, 22 civil archives, and one military archive. RESULTS: Apart from few
      exceptions, the results show the absence of a curatorial policy for the
      organization, access or even physical preservation of this material, frequently
      leading to unavailability, deterioration, and ultimately its complete loss.
      CONCLUSIONS: This study indicates the need to promote the preservation of a
      historical heritage that is a key to understanding historical epidemiological
      patterns and human responses to global health threats.

PMID- 29352632
TI  - Superior Vena Cava Syndrome Following Mitral Valve Repair.

PMID- 29352634
TI  - Factors influencing the recycling rate under the volume-based waste fee system in
      South Korea.
AB  - Since the early 2000s, the Republic of Korea (South Korea) has maintained its top
      rank status for its municipal solid waste (MSW) recycling rate among OECD
      (Organization for Economic Cooperation and Development) member countries. The
      volume-based waste fee system (VWF) has been considered to be the major factor
      contributing to the high recycling performance, and extant research has verified
      the positive relationship between VWF adoption and the MSW recycling rate.
      Nevertheless, there exists a gap in the literature, as past research has focused
      more on testing the positive effects of VWF rather than on investigating the
      determinants of recycling rates after the adoption of VWF. The current study
      seeks to address this gap by investigating the various factors that affect
      recycling rates under the VWF system. More specifically, using data from 16
      regions in South Korea over a period of 11 years, this study empirically tests
      the effects of VWF pricing, the citizen cost burden ratio for the VWF system, and
      pro-environmental behavior related to VWF on the recycling rate. The findings
      indicate that economic incentives such as cost savings on VWF plastic bag
      purchases and reduced burden from paying VWF expenses result in higher recycling
      rates. The findings also demonstrate that pro-environmental behavior in the VWF
      context positively affects the recycling rate.

PMID- 29352636
TI  - Beyond cut-off values for hypertension... individualize interventions.

PMID- 29352633
TI  - Current concerns and perspectives on Zika virus co-infection with arboviruses and
      HIV.
AB  - Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and
      sub-tropical regions has a complicated impact on the immunopathogenesis of other
      endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human
      immunodeficiency virus (HIV). The consequences of the possible co-infections with
      these viruses have specifically shown significant impact on the treatment and
      vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and
      Asian lineages that causes neurological complications in infected humans. Many of
      DENV and CHIKV endemic regions have been experiencing outbreaks of ZIKV
      infection. Intriguingly, the mosquitoes, Aedes Aegypti and Aedes Albopictus, can
      simultaneously transmit all the combinations of ZIKV, DENV, and CHIKV to the
      humans. The co-circulation of these viruses leads to a complicated immune
      response due to the pre-existence or co-existence of ZIKV infection with DENV and
      CHIKV infections. The non-vector transmission of ZIKV, especially, via sexual
      intercourse and placenta represents an additional burden that may hander the
      treatment strategies of other sexually transmitted diseases such as HIV.
      Collectively, ZIKV co-circulation and co-infection with other viruses have
      inevitable impact on the host immune response, diagnosis techniques, and vaccine
      development strategies for the control of these co-infections.

PMID- 29352635
TI  - [Palytoxin poisoning with soft coral from a tank in France: 3 cases reports].

PMID- 29352637
TI  - The ability of topical and systemic statins to increase osteogenesis around
      dental implants: a systematic review of histomorphometric outcomes in animal
      studies.
AB  - The purpose of this systematic review was to evaluate the quantitative
      histomorphometric outcomes of animal studies investigating statins as a pro
      osteogenic agent to enhance the osseointegration of dental implants. Some animal
      studies have suggested a beneficial action of statins on bone tissue. Electronic
      and manual literature searches, without date or language restriction, were
      performed by two independent review authors up to February 2017. Eligibility
      criteria included animal trials quantitatively analysing the pro-osteogenic
      effect of statins on dental implants. The quality of the included studies was
      assessed using the ARRIVE guidelines. The search and selection process yielded 12
      studies, published between 2004 and 2015. The experimental animals models used
      were rats and dogs. The statins used in the studies were simvastatin and
      fluvastatin, which were administered locally or systemically, or applied to the
      implant surface. All of the selected studies showed a statistically significant
      positive effect of statins on bone formation around implants. The mean quality
      assessment score (ARRIVE) of the studies was 11.5+/-2.27 out of a possible total
      of 25 points. The histomorphometric data from available preclinical studies
      suggest a positive effect of statins on increasing osteogenesis around dental
      implants.

PMID- 29352639
TI  - Indirect glyphosate detection based on ninhydrin reaction and surface-enhanced
      Raman scattering spectroscopy.
AB  - Glyphosate is one of the most commonly-used and non-selective herbicides in
      agriculture, which may directly pollute the environment and threaten human
      health. A simple and effective approach to assessment of its damage to the
      natural environment is thus quite necessary. However, traditional chromatography
      based detection methods usually suffer from complex pretreatment procedures.
      Herein, we propose a simple and sensitive method for the determination of
      glyphosate by combining ninhydrin reaction and surface-enhanced Raman scattering
      (SERS) spectroscopy. The product (purple color dye, PD) of the ninhydrin reaction
      is found to SERS-active and directly correlate with the glyphosate concentration.
      The limit of detection of the proposed method for glyphosate is as low as 1.43*10
      8mol.L-1 with a relatively wider linear concentration range (1.0*10-7-1.0*10
      4mol.L-1), which demonstrates its great potential in rapid, highly sensitive
      concentration determination of glyphosate in practical applications for safety
      assessment of food and environment.

PMID- 29352638
TI  - The evaluation of the hydrophilic-hydrophobic interactions and their effect in
      water-methanol solutions: A study in terms of the thermodynamic state functions
      in the frame of the transition state theory.
AB  - Aqueous solutions of amphiphilic molecules are characterized by the competition
      between hydrophilic and hydrophobic interactions. These interactions have a
      different energetic dependence with the temperature. Whereas hydrophilic
      interactions have been well characterized, a complete theory for the hydrophobic
      ones is still lacking as well as the comprehension of the effect that the solvent
      exerts on the solute and vice versa. In this paper from the measured relaxation
      time, we evaluated the thermodynamic state functions of water-methanol solutions
      in the frame of the transition state theory. In particular we study the behavior
      of the Gibbs free energy, enthalpy and entropy of water, methanol and some of
      their solutions as a function of both temperature and water molar fraction. Our
      results indicate that the temperature of about 280 K represents a crossover
      between two regions dominated by hydrophobicity (high T) and hydrophilicity (low
      T).

PMID- 29352640
TI  - Recent advancements in bioremediation of dye: Current status and challenges.
AB  - The rampant industrialization and unchecked growth of modern textile production
      facilities coupled with the lack of proper treatment facilities have proliferated
      the discharge of effluents enriched with toxic, baleful, and carcinogenic
      pollutants including dyes, heavy metals, volatile organic compounds, odorants,
      and other hazardous materials. Therefore, the development of cost-effective and
      efficient control measures against such pollution is imperative to safeguard
      ecosystems and natural resources. In this regard, recent advances in
      biotechnology and microbiology have propelled bioremediation as a prospective
      alternative to traditional treatment methods. This review was organized to
      address bioremediation as a practical option for the treatment of dyes by
      evaluating its performance and typical attributes. It further highlights the
      current hurdles and future prospects for the abatement of dyes via biotechnology
      based remediation techniques.

PMID- 29352641
TI  - Can You Do Health Disparities Research with Publicly Available Datasets?
AB  - RATIONALE AND OBJECTIVES: Given the growing importance of identifying and
      reducing health disparities, it is important for radiologist researchers to
      engage in this space to promote evidence-based imaging disparities policy.
      However, researchers are often hindered by access to appropriate data to perform
      quality research. MATERIALS AND METHODS: This paper reviews existing publicly
      available data sets that may be useful for performing imaging disparities
      research. RESULTS: Multiple data sources are publicly available and have been
      used by previous researchers to examine imaging disparities. CONCLUSIONS: This
      paper provides an overview of publicly available data sources that radiologists
      can use for imaging disparities research. Appropriate use of these data sources
      will require researchers to carefully consider the overall research question and
      level of analysis.

PMID- 29352642
TI  - LGALS4, CEACAM6, TSPAN8, and COL1A2: Blood Markers for Colorectal Cancer
      Validation in a Cohort of Subjects With Positive Fecal Immunochemical Test
      Result.
AB  - BACKGROUND: A noninvasive blood test for the early detection of colorectal cancer
      (CRC) is highly required. We evaluated a panel of 4 mRNAs as putative markers of
      CRC. MATERIALS AND METHODS: We tested LGALS4, CEACAM6, TSPAN8, and COL1A2,
      referred to as the CELTiC panel, using quantitative reverse transcription
      polymerase chain reaction, on subjects with positive fecal immunochemical test
      (FIT) results and undergoing colonoscopy. Using a nonparametric test and
      multinomial logistic model, FIT-positive subjects were compared with CRC patients
      and healthy individuals. RESULTS: All the genes of the CELTiC panel displayed
      statistically significant differences between the healthy subjects (n = 67), both
      low-risk (n = 36) and high-risk/CRC (n = 92) subjects, and those in the negative
      colonoscopy, FIT-positive group (n = 36). The multinomial logistic model revealed
      LGALS4 was the most powerful marker discriminating the 4 groups. When assessing
      the diagnostic values by analysis of the areas under the receiver operating
      characteristic curves (AUCs), the CELTiC panel reached an AUC of 0.91
      (sensitivity, 79%; specificity, 94%) comparing normal subjects to low-risk
      subjects, and 0.88 (sensitivity, 75%; specificity, 87%) comparing normal and high
      risk/CRC subjects. The comparison between the normal subjects and the negative
      colonoscopy, FIT-positive group revealed an AUC of 0.93 (sensitivity, 82%;
      specificity, 97%). CONCLUSION: The CELTiC panel could represent a useful tool for
      discriminating subjects with positive FIT findings and for the early detection of
      precancerous adenomatous lesions and CRC.

PMID- 29352643
TI  - Assessment of a source position checking tool for the quality assurance of
      transfer tubes used in HDR 192Ir brachytherapy treatments.
AB  - PURPOSE: The determination of source positions before treatment is an essential
      part of the quality assurance (QA) associated with high dose rate brachytherapy
      treatments. The purpose of this study was to design and commission a tool to
      allow the quantification of source positions across multiple transfer tube types.
      METHODS AND MATERIALS: A bespoke flexi-adapter jig, three transfer tube adapters,
      and a film piercing pointer were designed and built for source position QA across
      three transfer tube types-the standard, 6 French, and gynae transfer tubes. The
      jig was calibrated against a manufacturer source position check tool, and
      intratube and intertube source position variations investigated across a total of
      40 transfer tubes, using strips of Gafchromic film irradiated at multiple
      positions 20 mm apart with a microSelectron V3 afterloader (Elekta, Holland). The
      performance of the jig in localizing the nominal dwell positions relative to the
      manufacturer check tool was assessed. Associated expanded uncertainties were
      quantified in line with the International Organization for Standardization
      Guidelines. RESULTS: The mean expanded uncertainty associated with the use of the
      jig was 0.4 +/- 0.0 mm (k = 1). The performance of the jig was 0.3 +/- 0.0 mm,
      while the intratube and intertube source positional variations were observed to
      be within +/-1.0 mm across most transfer tubes. CONCLUSIONS: A bespoke flexi
      adapter jig capable of allowing source position measurements to be carried out on
      various transfer tube types has been designed. Measurement results highlight the
      need for routine QA of all transfer tubes in clinical use.

PMID- 29352644
TI  - Metastatic Brain Disease from Non-small Cell Lung Cancer - Getting Back to the
      Drawing Board.

PMID- 29352645
TI  - Diversity oriented synthesis of chromene-xanthene hybrids as anti-breast cancer
      agents.
AB  - A diverse library of chromene-xanthene hybrids were synthesized through
      intramolecular Friedel-Crafts reaction of the arenoxy carbinols. Examples include
      first incorporation of amino acid tyrosine into xanthene skeletons with polar
      functionalities. A careful structural evaluation revealed that tyrosine crafted
      chromene-xanthene hybrids exhibited good activities against breast cancer cell
      lines MCF-7, MDA-MB-231. The lead compound 16 displays significant cell cycle
      arrest at G1 phase and induces apoptosis in MDA-MB-231 cells.

PMID- 29352646
TI  - Synthesis and biological evaluation of anti-cancer agents that selectively
      inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2
      protein.
AB  - Compound JCC76 selectively inhibited the proliferation of human epidermal growth
      factor 2 (Her2) over-expressed breast cancer cells. In the current study, a
      ligand based structural optimization was performed to generate new analogs, and
      we identified derivatives 16 and 17 that showed improved activity and selectivity
      against Her2 positive breast cancer cells. A structure activity relationship
      (SAR) was summarized. Compounds 16 and 17 were also examined by western blot
      assay to check their effect on Her2 protein. The results reveal that the
      compounds could decrease the Her2 protein, which explains their selectivity to
      Her2 over-expressed breast cancer cells. Furthermore, the compounds inhibited the
      chaperone activity of small chaperone protein that could stabilize Her2 protein.

PMID- 29352648
TI  - Learning diversity in nurse education and practice - Current challenges,
      contemporary perspectives and innovative solutions.

PMID- 29352647
TI  - IFN-gamma and TNF-alpha Pre-licensing Protects Mesenchymal Stromal Cells from the
      Pro-inflammatory Effects of Palmitate.
AB  - The use of mesenchymal stromal cell (MSC) therapy for the treatment of type 2
      diabetes (T2D) and T2D complications is promising; however, the investigation of
      MSC function in the setting of T2D has not been thoroughly explored. In our
      current study, we investigated the phenotype and function of MSCs in a simulated
      in vitro T2D environment. We show that palmitate, but not glucose, exposure
      impairs MSC metabolic activity with moderate increases in apoptosis, while
      drastically affecting proliferation and morphology. In co-culture with peripheral
      blood mononuclear cells (PBMCs), we found that MSCs not only lose their normal
      suppressive ability in high levels of palmitate, but actively support and enhance
      inflammation, resulting in elevated PBMC proliferation and pro-inflammatory
      cytokine release. The pro-inflammatory effect of MSCs in palmitate was partially
      reversed via palmitate removal and fully reversed through pre-licensing MSCs with
      interferon-gamma and tumor necrosis factor alpha. Thus, palmitate, a specific
      metabolic factor enriched within the T2D environment, is a potent modulator of
      MSC immunosuppressive function, which may in part explain the depressed potency
      observed in MSCs isolated from T2D patients. Importantly, we have also identified
      a robust and durable pre-licensing regimen that protects MSC immunosuppressive
      function in the setting of T2D.

PMID- 29352649
TI  - Optimal use of peri-operative human chorionic gonadotrophin concentrations to
      identify persistent ectopic pregnancy after laparoscopic salpingostomy: a
      retrospective cohort study.
AB  - The aim of this study was to improve clinical decision-making for the
      identification of persistent ectopic pregnancy after linear salpingostomy. The
      study identified 854 laparoscopic salpingostomies performed between 2011 and
      2016; 794 had a human chorionic gonadotrophin (HCG) <10 mIU/ml documented in the
      electronic medical record within 1 month after surgery ('successes'). Sixty (7%)
      received either methotrexate or repeat surgery for persistent ectopic pregnancy
      ('failures'). Five hundred and seventeen, including 46 'failures', had two or
      more immediate post-operative HCG measurements available. The most clinically
      useful prediction rule was calculated by dividing the difference between the
      first and second post-operative HCG values by the first post-operative HCG value
      (i.e. [HCG1 - HCG2]/HCG1). When this ratio exceeded 0.75, it reliably ruled out
      persistent ectopic with a negative predictive value = 99%. When this ratio was
      less than 0.2, it identified persistent ectopics with a positive predictive value
      = 88%. It appears that this simple arithmetic calculation involving two early
      post-operative HCG values may allow for efficient triage of patients before post
      operative day 5. If validated in prospective studies, this could help minimize
      the risk, inconvenience and expense of requiring several weeks of frequent follow
      up to rule in/rule out persistent ectopic pregnancy.

PMID- 29352650
TI  - Cryptococcus gattii genotype VGIIa infection imported from Vancouver Island to
      Japan.
AB  - A 71-year-old Japanese man with travel history to the Vancouver Island, Canada
      was diagnosed the pulmonary and central nervous system infections caused by
      Cryptococcus gattii genotype VGIIa. This is the first imported case of
      Cryptococcus gattii genotype VGIIa infection from endemic area of North America
      to Japan. He was recovery with no residual neurological dysfunction by early
      resection of brain mass and antifungal therapy. Early surgical resection of
      cerebellar cryptococcoma may shorten the length of induction therapy with
      antifungal drugs.

PMID- 29352652
TI  - Commentary on "Predictors of Change in the Ankle Brachial Index with Exercise".

PMID- 29352651
TI  - Catheter Injected Bone Marrow Mesenchymal Stem Cells Induce Efficacious Occlusion
      of Arteriovenous Nidus in a Swine Model.
AB  - OBJECTIVES: Arteriovenous malformations (AVMs) are complex vascular lesions.
      Surgical excision is the treatment of choice, but is often not achievable. Embolo
      sclerotherapy alone is associated with high recurrence rates. This study tested
      the hypothesis that seeding hydrogel conditioned bone marrow derived
      mesenchymatous stem cells (BM-MSCs) in an AVM nidus model induces solid
      microvascular occlusion through endoluminal tissue growth. METHODS: AVMs were
      modelled as arteriovenous microvascular nidus, using swine rete mirabile, a
      plexiform intracranial structure composed of arterial microvessels that
      extensively anastomose. A right carotid-jugular fistula was created to generate
      high flow in the rete, and bone marrow was aspirated. At day 14, cultured BM-MSCs
      marked with a red fluorochrome were incorporated into a hyaluronic acid hydrogel,
      and injected through a catheter into the rete mirabile, using femoral access. In
      specific groups microsphere embolisation immediately preceded gel injection. At
      day 28, the swine were euthanased and the rete mirabile harvested for qualitative
      and quantitative analysis of microvessel lumen occlusion. RESULTS: Actual
      transfer of PKH26 labelled cells in rete was confirmed. In a first phase of the
      study, five swine died as a result of neurological events, prompting reductions
      of the injected volumes. Twenty-three animals survived until day 28. Injection of
      BM-MSC loaded hydrogel (n=6) significantly increased the occlusion rate compared
      with injection of acellular hydrogel (n=7) (10% [range, 10-12%] vs. 26% [range,
      20-41%], p=.016). Injection of BM-MSC loaded hydrogel immediately after
      microspheres (n=6) enhanced the occlusion rate compared with embolic microspheres
      alone (n=6) (50% [range 46-56%] vs. 22% [range, 15-27%] p=.045). Microsphere
      injection resulted in vascular luminal thrombus formation. Injection of BM-MSCs
      induced endoluminal growth of vascular smooth muscle cells with cell
      proliferation and a dense collagen rich extracellular matrix. CONCLUSION: The
      luminal occlusion pattern of a microvascular AVM like structure can be changed
      from thrombus to solid cellular accumulation. The possibility of injecting living
      cells in a microvascular network, in a chronic survival model, provides new tools
      for research and treatment of AVMs and other microvascular diseases.

PMID- 29352653
TI  - Commentary on "Catheter Injected Bone Marrow Mesenchymal Stem Cells Induce
      Efficacious Occlusion of Arteriovenous Nidus in a Chronic Swine Model".

PMID- 29352654
TI  - Resistance training during a 12-week protein supplemented VLCD treatment enhances
      weight-loss outcomes in obese patients.
AB  - BACKGROUND: This investigation evaluated the efficacy by which resistance
      training enhances body composition, metabolic, and functional outcomes for obese
      patients undergoing a 12-week medically supervised hypocaloric treatment.
      METHODS: This was a single-blind, randomized, parallel-group prospective trial.
      Morbidly obese patients were prescribed a 12-week proprietary very low calorie
      diet (VLCD) treatment (Optifast(r)) with supplemental protein (1120 kcals/day)
      and were placed in one of two groups for 14 weeks: 1) Standard Treatment Control
      (CON) (n = 5) or 2) Resistance Training (RT) (n = 6). Both groups underwent a
      pedometer-based walking program; however only RT performed resistance training 3
      days/week for 12 weeks. Body composition, resting energy expenditure (REE),
      neuromuscular function, and serum biomarkers were measured at weeks 0, 6, and 13.
      RESULTS: Both groups exhibited a significant loss of total body mass (TBM) (CON: 
      19.4 +/- 2.3 kg, p = 0.0009 vs. RT: -15.8 +/- 1.5 kg, p = 0.0002) and fat mass
      (FM) (CON: -14.7 +/- 1.8 kg, p = 0.0002 vs. RT: -15.1 +/- 2.1 kg, p = 0.0002)
      with no group differences. CON lost 4.6 +/- 0.8 kg (p = 0.004) of lean mass (LM)
      while RT demonstrated no changes. Group differences were found for the relative
      proportion of total weight-loss due to FM-loss (CON: 75.6 +/- 3.4% vs. RT: 96.0
      +/- 6.0%, p = 0.03) and LM-loss (CON: 24.4 +/- 3.2% vs. RT: 4.0 +/- 6.5%, p =
      0.03). CON demonstrated a 328.6 +/- 72.7 kcal/day (-14.3 +/- 2.4%) (p = 0.02)
      decrease in REE while RT exhibited a non-significant decrease of 4.6 +/- 1.6% (p
      = 0.78). RT demonstrated greater improvements in all measures of contractile
      function and strength when compared to CON (p < 0.05). At post-treatment, RT
      exhibited greater serum free fatty acids (p = 0.01), glycerol (p = 0.003), and
      beta-hydroxybutyrate (p = 0.005) than CON. CONCLUSION: Resistance training was
      advantageous for weight-loss composition by preservation of LM without
      compromising overall weight- or fat-loss in morbidly obese men and women
      undergoing a protein supplemented VLCD. These changes accompanied positive
      adaptations for resting metabolism and muscular function.

PMID- 29352656
TI  - Smoking status and diet quality.

PMID- 29352655
TI  - Legume consumption and risk of all-cause, cardiovascular, and cancer mortality in
      the PREDIMED study.
AB  - BACKGROUND & AIMS: Limited prospective studies have examined the association
      between legumes consumption and mortality, whereas scarce, if at all, previous
      studies have evaluated such associations taking into consideration specific grain
      legumes. We aimed to investigate the association between total legumes
      consumption and grain legumes species (dry beans, chickpeas, lentils, and fresh
      peas) with all-cause, cardiovascular disease (CVD), cancer and other-cause
      mortality among elderly Mediterranean individuals at high CVD risk. METHODS: We
      prospectively assessed 7216 participants from the PREvencion con DIeta
      MEDiterranea study. Dietary intake was assessed at baseline and yearly during
      follow-up by using a validated food frequency questionnaire. RESULTS: During a
      median follow-up of 6.0 years, 425 total deaths, 103 CVD deaths, 169 cancer
      deaths and 153 due to other-causes deaths occurred. Hazard ratios (HRs) [95%
      confidence interval (CI)] of CVD mortality were 1.52 (1.02-2.89) (P-trend =
      0.034) and 2.23 (1.32-3.78) (P-trend = 0.002) for the 3rd tertile of total
      legumes and dry beans consumption, respectively, compared with the 1st tertile.
      When comparing extreme tertiles, higher total legumes and lentils consumption was
      associated with 49% (HR: 0.51; 95% CI: 0.31-0.84; P-trend = 0.009) and 37% (HR:
      0.63; 95% CI: 0.40-0.98; P-trend = 0.049) lower risk of cancer mortality. Similar
      associations were observed for CVD death in males and for cancer death in males,
      obese and diabetic participants. CONCLUSIONS: These findings support the benefits
      of legumes consumption for cancer mortality prevention which may be
      counterbalanced by their higher risk for CVD mortality. TRIAL REGISTRATION: The
      trial is registered at http://www.controlled-trials.com (ISRCTN35739639).
      Registration date: 5th October 2005.

PMID- 29352657
TI  - Electroencephalographic monitoring for seizure identification and prognosis in
      term neonates.
AB  - Seizures represent a manifestation of neurological disease in the neonatal
      period. Historically, neonatal seizures were identified by direct clinical
      observation. However, since most seizures are electroencephalographic (EEG)-only
      (subclinical, non-convulsive) and clinical manifestations may be subtle, many
      clinicians place increasing importance on EEG data including conventional EEG or
      amplitude-integrated EEG to identify seizures in neonates. Beyond seizure
      identification, the EEG is a robust source of information about brain function
      that can be useful for neurobehavioral prognostication in some neonates. This
      review summarizes the available data regarding EEG for neonatal seizure diagnosis
      and brain function assessment.

PMID- 29352658
TI  - Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse
      obstructed kidney: Special references to HIF-1 dependent gene expression of
      profibrogenic molecules.
AB  - The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1)
      in the development of renal fibrosis in mouse obstructive nephropathy. We used
      mice with floxed HIF-1alpha alleles and tamoxifen-inducible Cre/ERT2 recombinase
      under ubiquitin C promoter to induce global HIF-1alpha deletion. Following
      tamoxifen administration, mice were subjected to unilateral ureteral obstruction
      (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and
      interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl
      hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at
      3 and 7 days but not at 14 days after UUO. Various factors promoting fibrosis
      were up-regulated during the development of fibrosis. HIF-1 dependent gene
      expression of profibrotic molecules, plasminogen activator inhibitor 1,
      connective tissue growth factor, lysyl oxidase like 2 and transglutaminase 2 was
      observed in the obstructed kidney but such HIF-1 dependency was limited to the
      early onset of renal fibrosis. Global HIF-1 deletion tended to attenuate
      interstitial collagen I deposition at 3 days but had no effects thereafter. It is
      suggested that HIF-1 dependent profibrogenic mechanisms are operating at the
      early onset of renal fibrosis but its contribution declines with the progression
      in mouse UUO model.

PMID- 29352659
TI  - Microwave ablation provides better survival than liver resection for
      hepatocellular carcinoma in patients with borderline liver function: application
      of ALBI score to patient selection.
AB  - BACKGROUND: Studies comparing microwave ablation (MWA) and liver resection are
      lacking. This study evaluates the survival of patients with hepatocellular
      carcinoma (HCC) treated with liver resection or MWA and the role of Albumin
      Bilirubin (ALBI) score in patient selection for treatments. METHODS: This is a
      retrospective analysis of patients who received curative liver resection or MWA
      for HCC. Propensity score matching was used at a 1:1 ratio. The value of ALBI
      grade for patient selection was evaluated. Overall and disease-free survival were
      compared between two groups. RESULTS: Of the 442 patients underwent MWA or liver
      resection for HCC during the study period, 63 patients received MWA and 379
      patients received liver resection. Propensity scoring matching analysis resulted
      in 63 matched pairs for further analysis. Subgroup analysis according to the ALBI
      grade was performed. Liver resection offered better overall and disease-free
      survivals in patients with ALBI grade 1. MWA provided a significantly better
      overall survival (p = 0.025) and a trend towards better disease-free survival (p
      = 0.39) in patients with ALBI grade 2 or 3. CONCLUSIONS: Liver resection offered
      superior disease-free survival to MWA in patients with HCC. The ALBI grade could
      identify patients with worse liver function who might gain survival advantage
      from MWA.

PMID- 29352660
TI  - Clinical significance of MUC13 in pancreatic ductal adenocarcinoma.
AB  - BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack
      of an effective early diagnostic biomarker. This study elucidates significance of
      MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in
      tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and
      analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT
      PCR, computational and submicron scale mass-density fluctuation analyses, ROC and
      Kaplan Meir curve analyses. RESULTS: MUC13 expression was detected in 100%
      pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS =
      5.8; AUC >0.8, P < 0.0001), 94.6% of pancreatic ductal adenocarcinoma (PDAC)
      samples (MCS = 9.7, P < 0.0001) as compared to low expression in tumor adjacent
      tissues (MCS = 4, P < 0.001) along with faint or no expression in normal
      pancreatic tissues (MCS = 0.8; AUC >0.8; P < 0.0001). Nuclear MUC13 expression
      positively correlated with nodal metastasis (P < 0.05), invasion of cancer to
      peripheral tissues (P < 0.5) and poor patient survival (P < 0.05; prognostic AUC
      = 0.9). Submicron scale mass density and artificial intelligence based algorithm
      analyses also elucidated association of MUC13 with greater morphological disorder
      (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and
      poor patient survival. CONCLUSION: This study provides significant information
      regarding MUC13 expression/subcellular localization in PanCa samples and
      supporting the use anti-MUC13 MAb for the development of PanCa
      diagnostic/prognostic test.

PMID- 29352661
TI  - Mechanistic insights into the genetics of affective psychosis from Prader-Willi
      syndrome.
AB  - Schizophrenia and bipolar disorder are common, severe, and disabling psychotic
      disorders, which are difficult to research. We argue that the genetically
      determined neurodevelopmental disorder Prader-Willi syndrome (PWS), which is
      associated with a high risk of affective psychotic illness, can provide a window
      into genetic mechanisms and associated neural pathways. People with PWS can all
      show non-psychotic psychopathology and problem behaviours, but the prevalence of
      psychotic illness differs markedly by genetic subtype; people with PWS due to
      chromosome 15 maternal uniparental disomy have higher prevalence of psychotic
      illness compared with patients with PWS due to 15q11-13 deletions of paternal
      origin. On the basis of this observation and the neural differences between
      genetic subtypes, we hypothesise that the combined effects of the absent
      expression of specific maternally imprinted genes at 15q11-13, and excess
      maternally imprinted or paternally expressed genes on chromosome 15, affect the
      gamma-aminobutyric acid-glutamatergic pathways and associated neural networks
      that underpin mood regulation and sensory processing, resulting in psychotic
      illness. We propose a model of potential mechanisms of psychosis in PWS, which
      might be relevant in the general population, and should inform future research.

PMID- 29352662
TI  - Distinct progression patterns of brain disease in infantile and juvenile
      gangliosidoses: Volumetric quantitative MRI study.
AB  - BACKGROUND: GM1-gangliosidosis and GM2-gangliosidosis (Tay-Sachs disease and
      Sandhoff disease) are unrelenting heritable neurodegenerative conditions of
      lysosomal ganglioside accumulation. Although progressive brain atrophy is
      characteristic, longitudinal quantification of specific brain structures has not
      been systematically studied. OBJECTIVES: The goal of this longitudinal study has
      been to quantify and track brain MRI volume changes, including specific structure
      volume changes, at different times in disease progression of childhood
      gangliosidoses, and to explore quantitative brain MRI volumetry (qMRI) as a non
      invasive marker of disease progression for future treatment trials. METHODS:
      Brain qMRI studies were performed in 14 patients with gangliosidoses (9
      infantile, 5 juvenile) yearly. Cerebellar cortex and white matter, caudate,
      putamen, corpus callosum, ventricles, total brain, and intracranial volumes were
      measured, as well as total brain volume. Age-matched controls were available for
      the patients with the juvenile phenotype. RESULTS: The infantile phenotype of all
      gangliosidoses showed a consistent pattern of macrocephaly and rapidly increasing
      intracranial MRI volume with both (a) brain tissue volume (cerebral cortex and
      other smaller structures) and (b) ventricular volume (P<0.01 for all). In
      contrast to apparent enlargement of the total brain volume, and chiefly the
      enlarged cerebral cortex, a subset of smaller brain substructures generally
      decreased in size: the corpus callosum, caudate and putamen became smaller with
      time. The volume of cerebellar cortex also decreased in patients with infantile
      GM1-gangliosidosis and juvenile GM1- and GM2-gangliosidosis; however, infantile
      GM2-gangliosidosis cerebellar cortex was the exception, increasing in size.
      Elevated intracranial pressure (estimated by lumbar spinal pressure) was a common
      finding in infantile disease and showed continued increases as the disease
      progressed, yet lacked MRI signs of hydrocephalus except for increasing
      ventricular size. Notably, in patients with juvenile gangliosidosis, macrocephaly
      and elevated intracranial pressure were absent and total brain volume decreased
      with time compared to controls (P=0.004). CONCLUSIONS: The disease course of
      infantile versus juvenile gangliosidoses is clearly distinguished by the rate of
      brain disease progression as characterized by qMRI. Assessments by qMRI represent
      a robust non-invasive method for monitoring CNS changes in the clinical course of
      gangliosidoses and is ideally suited to monitor effects of novel CNS-directed
      therapies in future clinical trials.

PMID- 29352663
TI  - Early versus delayed closure of bladder exstrophy: A National Surgical Quality
      Improvement Program Pediatric analysis.
AB  - INTRODUCTION: Delayed closure of bladder exstrophy has become more popular;
      however, there is limited the evidence of its success. Existing literature
      focuses on intermediate and long-term outcomes, and short-term postoperative
      outcomes are limited by the small number of cases and varying follow-up methods.
      OBJECTIVE: The objectives of the current study were to: 1) compare 30-day
      complications after early and delayed closure of bladder exstrophy, and 2)
      evaluate practice patterns of bladder exstrophy closure. STUDY DESIGN: The
      National Surgical Quality Improvement Program Pediatric (NSQIPP) database from
      2012 to 2015 was reviewed for all cases of bladder exstrophy closure. Early
      closure was defined as surgery at age 0-3 days, and delayed closure was defined
      as age 4-120 days at time of surgery. Demographic, clinical, and peri-operative
      characteristics were collected, as were postoperative complications,
      readmissions, and re-operations up to 30 days. Descriptive statistics were
      performed, and multivariate linear and logistic regression analyses were
      performed for salient complications. RESULTS: Of 128 patients undergoing bladder
      exstrophy closure, 62 were included for analysis, with 44 (71%) undergoing
      delayed closure. Mean anesthesia and operative times were greater in the delayed
      closure group, and were associated with more concurrent procedures, including
      inguinal hernia repairs and osteotomies. The delayed closure group had a higher
      proportion of 30-day complications, due to a high rate of blood transfusion (57%
      vs 11%). Wound dehiscence occurred in 6/44 (14%) delayed closures, as compared
      with 0/18 (0%) early closures. When compared with prior published reports of
      national data from 1999 to 2010, delayed closure was performed more frequently in
      this cohort (71% vs 27%). DISCUSSION: The NSQIPP provides standardized reporting
      of peri-operative characteristics and 30-day complications, allowing a comparison
      of early to delayed closure of bladder exstrophy across multiple institutions.
      Assessing short-term risks in conjunction with long-term follow-up is crucial for
      determining optimal management of this rare but complex condition. CONCLUSION:
      Delayed closure of bladder exstrophy is performed frequently, yet it carries a
      high rate of 30-day complications worthy of further investigation. This can be
      useful in counseling patients and families, and to understand practice patterns
      across the country.

PMID- 29352664
TI  - Oral corticosteroids reduce length of hospital stay for preschool children with
      virus-associated wheeze.

PMID- 29352665
TI  - Complementary and alternative medicine (CAM) practices and dietary patterns in
      children with inflammatory bowel disease in Singapore and Malaysia.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) has been
      associated with adverse effects and self-imposed dietary restrictions. The
      prevalence of its use in Asian children with inflammatory bowel disease (IBD) is
      unknown. We aimed to determine the prevalence, types, and factors associated with
      the use of CAM among children with IBD from Singapore and Malaysia, and to
      ascertain if dietary restriction was prevalent in patients who used CAM. METHODS:
      A cross-sectional study was conducted in which parents of children with IBD
      attending two tertiary pediatric IBD referral centres in Singapore and Malaysia
      were interviewed. Data about demographics, conventional treatment, complementary
      therapies and dietary patterns were collected in a questionnaire. RESULTS: Of 64
      children with IBD interviewed, 83% (n = 53) reported the use of CAM (Singapore
      [90%] vs. Malaysia [76%]; p = 0.152). The median number of CAM agents used was
      two (range 1-10). The three most common types of CAM used were probiotics (64%),
      vitamin and mineral supplements (55%), and food-based therapies (36%). Among
      individual CAM categories, the use of food-based therapies was correlated
      significantly with nationality (r = 0.497, p < 0.001), history of weight loss due
      to IBD (r = 0.340, p = 0.013) and avoidance of certain foods to prevent a relapse
      (r = 0.289, p = 0.036). Parents who rated their child's disease activity as more
      severe were less likely to use CAM (r = -0.257, p = 0.041). Fifty-nine percent of
      CAM users reported physician awareness of their CAM use. The overall self
      perceived efficacy of CAM in improving IBD symptoms was 34%. Of the dietary
      patterns explored, only intake of dairy products was associated with CAM use (r =
      0.306, p = 0.019). CONCLUSION: Use of CAM is prevalent in children with IBD in
      Malaysia and Singapore. Further studies to elucidate reasons influencing CAM use,
      dietary patterns and efficacy of commonly used CAM would be required.

PMID- 29352666
TI  - Handling, processing and disposal of stem cell products in Europe: A survey by
      the cellular therapy and immunobiology working party of the European Society for
      Blood and Marrow Transplantation.
AB  - BACKGROUND: There is considerable heterogeneity in processing of stem cells for
      hematopoietic stem cell transplantation across Europe. The Foundation for the
      Accreditation of Cellular Therapy (FACT)-Joint Accreditation Committee
      International Society for Cellular Therapy and European Society for Blood and
      Marrow Transplantation (EBMT) (JACIE) standards provide minimum guidelines that,
      however, leave room for significant variations in practices at the individual
      transplantation center (TC). METHODS: To better understand the extent of
      heterogeneity in storage conditions, quality controls (QCs), graft processing and
      disposal, a questionnaire was developed, reviewed by the Cellular Therapy and
      Immunobiology Working Party (CTIWP) and sent to all EBMT TCs. RESULTS: In this
      study, 288 TCs from 46 countries (32 European, 14 associated) responded to the
      survey. Long-term storage is performed mainly either in liquid nitrogen or in the
      vapor phase of liquid nitrogen with 10% dimethyl sulfoxide (DMSO; 58% of
      centers). In case of microbiological contamination, most TCs make a case-by-case
      decision in collaboration with the clinicians. CD34+ counts are performed
      routinely either before and/or after thawing. Some centers perform additional
      QCs. DMSO is generally not removed (83%) and the graft is thawed at the bedside
      (68%) in a water bath (78%). There is heterogeneity between the centers regarding
      duration of storage and graft disposal. DISCUSSION: Overall, this survey
      demonstrates that the majority of responding TCs uses standardized procedures
      (intracenter standardization). However, significant intercenter variations
      persist, which warrant further standardization and investigations on clinical and
      financial consequences. Additionally, efforts should be undertaken to provide
      more specific international guidelines on storage duration and graft disposal,
      which may also have an important impact on health care services worldwide.

PMID- 29352667
TI  - An intriguing link between human leukocyte antigen G, T-regulatory cells and
      neutrophil gelatinase-associated lipocalin in immune tolerance induction.

PMID- 29352668
TI  - The effect of single and repeated prefrontal intermittent theta burst stimulation
      on cortical reactivity and working memory.
AB  - BACKGROUND: With an increasing interest in the use of theta burst stimulation
      (TBS) as a cognitive enhancer and a potential therapeutic tool for psychiatric
      disorders, there is a need to identify optimal parameters of TBS in the
      prefrontal cortex. OBJECTIVE/HYPOTHESIS: This study examined the effect of two
      blocks of prefrontal intermittent TBS (iTBS) on cortical reactivity and working
      memory performance, compared to one block of iTBS and sham stimulation. We
      hypothesized that greater cortical effects would be obtained with two blocks of
      iTBS. METHODS: Eighteen healthy participants attended three experimental sessions
      and received either sham, one block or two blocks of iTBS with a 15-min interval.
      Concurrent transcranial magnetic stimulation with electroencephalography (TMS
      EEG) was used to assess the change in cortical reactivity via TMS-evoked
      potentials. Working memory performance was assessed using the N-back task.
      Cluster-based permutation statistics and two-way ANOVAs were used for
      neurophysiological and behavioural data, respectively. RESULTS: Both single and
      two blocks of iTBS resulted in a significant increase in the amplitude of TMS
      evoked N100 and P200. No significant differences were observed between active
      conditions in either neurophysiological changes or working memory performance,
      and both failed to improve working memory performance relative to sham.
      CONCLUSIONS: Two blocks of iTBS did not result in stronger measured effects as
      compared to one block of iTBS. Future studies are needed to identify the optimal
      stimulation pattern in order to achieve a desired effect. It is also important to
      establish the best approach in quantifying neuromodulatory effects targeting the
      prefrontal cortex.

PMID- 29352669
TI  - TMS of primary motor cortex with a biphasic pulse activates two independent sets
      of excitable neurones.
AB  - BACKGROUND: Biphasic pulses produced by most commercially available TMS machines
      have a cosine waveform, which makes it difficult to study the interaction between
      the two phases of stimulation. OBJECTIVE: We used a controllable pulse TMS (cTMS)
      device delivering quasi-rectangular pulse outputs to investigate whether
      monophasic are more effective than biphasic pulses. METHODS: Temporally symmetric
      ("biphasic") or highly asymmetric ("monophasic") charge-balanced biphasic stimuli
      were used to target the hand area of motor cortex in the anterior-posterior (AP)
      or posterior-anterior (PA) initial current direction. RESULTS: We observed the
      lowest motor thresholds and shortest motor evoked potential (MEP) latencies with
      initial PA pulses, and highest thresholds and longest latencies with AP pulses.
      Increasing pulse symmetry tended to increase threshold with a PA direction
      whereas it lowered thresholds and shortened latencies with an AP direction.
      Furthermore, it steepened the MEP input-output curve with both directions.
      CONCLUSIONS: "Biphasic" TMS pulses can be viewed as two monophasic pulses of
      opposite directions, each stimulating a different set of interneurons with
      different thresholds (PA < AP). At threshold, the reverse phase of an initially
      PA pulse increases threshold compared with "monophasic" stimulation. At higher
      intensities, the reverse phase begins to activate AP-sensitive neurones and
      increase the effectiveness of stimulation above that of a "monophasic" PA pulse.
      "Biphasic" stimulation with initially AP pulses is dominated at threshold by
      activation produced by the lower threshold reverse (PA) phase. SIGNIFICANCE: The
      effects of biphasic stimulation are best understood as the summed output of two
      independent sets of directionally selective neural populations.

PMID- 29352670
TI  - Poor outcomes of out-of-hospital cardiac arrest at dinnertime in the elderly:
      Diurnal and seasonal variations.
AB  - PURPOSE: To investigate differences in chronological variations in
      characteristics and outcomes of out-of-hospital cardiac arrests (OHCAs) between
      elderly and non-elderly patients. METHODS: We retrospectively analyzed bystander
      witnessed OHCAs without prehospital involvement of physicians between January
      2007 and December 2014 in Japan. We considered the following time periods: night
      time (23:00-5:59) and non-night-time; we further divided non-night-time into
      dinnertime (18:00-20:29) and other non-night-time. Subsequently, we analyzed
      chronological variations in factors associated with OHCA survival using
      univariate and multivariable logistic regression analyses for unmatched and
      propensity-matched pairs, respectively. RESULTS: For elderly (>=65 years old, N =
      201,073) and non-elderly (>=10, <65 years old, N = 57,124) OHCA patients,
      survival rates were lower during night-time than during non-night-time (elderly,
      2.8% vs 1.6%; non-elderly, 9.8% vs 7.7%). The trend for incidences of bystander
      witnessed OHCA in the elderly showed three peaks associated with breakfast-time,
      lunchtime, and dinnertime. However, a transient but considerable decrease in
      survival rates was observed at dinnertime (1.9% at dinnertime and 3.0% during
      other non-night-time). OHCAs in the elderly at dinnertime were characterized by
      low proportions of presumed cardiac etiologies and shockable initial rhythm.
      However,even after adjusting for these and other factors associated with
      survival,survival rates were significantly lower at dinnertime than during other
      non-night-time for elderly OHCA patients (adjusted odds ratio, 1.29; 95%
      confidence interval, 1.18-1.41, with dinnertime as reference). This difference
      was significant even after propensity matching with significant augmentation in
      winter. CONCLUSIONS: Dinnertime, particularly in winter, is associated with lower
      survival in elderly OHCA patients.

PMID- 29352671
TI  - Does a major football event affect obstetric emergency attendances? A prospective
      observational study during Euro 2016.

PMID- 29352672
TI  - Physician expertise and cultural issues may play role in the results of
      ultrasound guided inter-scalene brachial plexus block.

PMID- 29352674
TI  - The effect of vertical split-flow patient management on emergency department
      throughput and efficiency.
AB  - BACKGROUND: To address emergency department overcrowding operational research
      seeks to identify efficient processes to optimize flow of patients through the
      emergency department. Vertical flow refers to the concept of utilizing and
      assigning patients virtual beds rather than to an actual physical space within
      the emergency department to care of low acuity patients. The aim of this study is
      to evaluate the impact of vertical flow upon emergency department efficiency and
      patient satisfaction. METHODS: Prospective pre/post-interventional cohort study
      of all intend-to-treat patients presenting to the emergency department during a
      two-year period before and after the implementation of a vertical flow model.
      RESULTS: In total 222,713 patient visits were included in the analysis with
      107,217 patients presenting within the pre-intervention and 115,496 in the post
      intervention groups. The results of the regression analysis demonstrate an
      improvement in throughput across the entire ED patient population, decreasing
      door to departure time by 17 min (95% CI 15-18) despite an increase in patient
      volume. No statistically significant difference in patient satisfaction scores
      were found between the pre- and post-intervention. CONCLUSIONS: Initiation of a
      vertical split flow model was associated with improved ED efficiency.

PMID- 29352673
TI  - Chest pain in a young female.
AB  - Acute Coronary Syndrome (ACS) is a common diagnosis in the emergency department
      (ED), the most severe manifestation of which is ST elevation on electrocardiogram
      (ECG). ST elevation reflects obstruction of flow through the coronary arteries,
      most commonly due to coronary atherosclerotic plaque rupture. However,
      alternative causes of coronary obstruction causing ST elevation are possible.
      Spontaneous coronary artery dissection (SCAD) is an unusual cause of ST elevation
      in ED patients which providers may encounter in patients without traditional
      atherosclerosis risk factors. Patients presenting with SCAD as a cause of ST
      elevation require unique management from traditional ACS. Here we report a case
      of a 43 year old female presenting with chest pain and unusual ECG findings
      including accelerated idioventricular rhythm followed by subtle ST segment
      elevation and resolution of abnormalities. This case illustrates subtle clinical
      and ECG findings suggestive of SCAD which emergency physicians should consider
      when evaluating patients for ACS in the absence of traditional clinical
      presentations. Such considerations may prompt physicians to avoid therapy for
      coronary plaque rupture which is not indicated in patients with SCAD.

PMID- 29352675
TI  - Impact of intestinal mannitol on hyperammonemia, oxidative stress and severity of
      hepatic encephalopathy in the ED.
AB  - : Hyperammonemia results from hepatic inability to remove nitrogenous products
      generated by protein metabolism of intestinal microbiota, which leads to hepatic
      encephalopathy (HE) in chronic liver disease (CLD). In ammonium neurotoxicity,
      oxidative stress (OxS) plays a pathogenic role. Our objective was to evaluate if
      intestinal mannitol is as effective and safe as conventional treatment for
      diminishing hyperammonemia, OxS, and HE in patients with CLD. MATERIAL AND
      METHODS: We included 30 patients with HE classified by "Haven Criteria for
      Hepatic Encephalopathy". They were randomized into two groups: 1) Mannitol Group
      (MG) with mannitol 20% administered into the intestine by an enema, 2)
      conventional group (CG) with lactulose 40 g enema both substances were diluted in
      800 mL of double distilled solution every 6 h; all patients received neomycin. We
      evaluated ammonia concentration, plasma oxidative stress, HE severity, intestinal
      discomfort and adverse effects. RESULTS: Hyperammonemia (171 +/- 104 vs 79 +/- 49
      MUmol ammonia/L, p < 0.01), and oxidative stress (MDA 29 vs 27%, formazan 15 vs
      11%, carbonyls 16 vs 9% and dityrosines 10 vs 5%) were reduced in MG and CG
      respectively. The HE severity decreased by two degrees compared to baseline
      values in both groups. Intestinal discomfort and electrolyte plasma alterations
      were less frequent (p < 0.05) in MG than CG. CONCLUSIONS: Intestinal mannitol is
      as effective and safe as conventional treatment for reducing hyperammonemia,
      oxidative stress, and hepatic encephalopathy of CLD patients in the emergency
      room. Likewise, mannitol is better tolerated than conventional treatment.

PMID- 29352677
TI  - Surface structure and tribology of legless squamate reptiles.
AB  - Squamate reptiles (around 10,000 species of snakes and lizards) comprise a myriad
      of distinct terrestrial vertebrates. The diversity within this biological group
      offers a great opportunity for customized bio-inspired solutions that address a
      variety of current technological problems especially within the realm of surface
      engineering and tribology. One subgroup within squamata is of interest in that
      context, namely the legless reptiles (mainly snakes and few lizards). The promise
      of that group lies within their functional adaptation as manifested in optimized
      surface designs and locomotion that is distinguished by economy of effort even
      when functioning within hostile tribological environments. Legless reptiles are
      spread over a wide range in the planet, this geographical diversity demands
      customized response to local habitats. Customization, in turn, is facilitated
      through specialized surface design features. In legless reptiles, micro elements
      of texture, their geometry and topological layout advance mitigation of
      frictional effects both in locomotion and in general function. Lately, the
      synergy between functional traits and intrinsic surface features has emerged as
      focus of research across disciplines. Many investigations have sought to
      characterize the structural as well as the tribological response of legless
      species from an engineering point of view. Despite the sizable amount of data
      that have accumulated in the literature over the past two decades or so, no
      effort to review the available information, whence this review. This manuscript,
      therefore, endeavors to assess available data on surface metrology and
      tribological behavior of legless reptiles and to define aspects of that
      performance necessary to formulate an advanced paradigm for bio-inspired surface
      engineering.

PMID- 29352676
TI  - Cardiorespiratory dynamics of rescuers during cardiopulmonary resuscitation in a
      hypoxic environment.
AB  - OBJECTIVE: We had previously experienced a case involving prolonged
      cardiopulmonary resuscitation (CPR) on Mt. Fuji (3776 m), demanding strenuous
      work by the rescuers. The objective of this study was to compare the effect of
      compression-only and conventional CPR on oxygen saturation of rescuers in a
      hypoxemic environment. METHODS: Changes in percutaneous arterial oxygen
      saturation (SpO2) and heart rate during CPR action were measured in a hypobaric
      chamber with barometric pressure adjusted to be equivalent to 3700 m above sea
      level (630-640 hPa). Thirty-three volunteers performed CPR with or without
      breaths using a CPR mannequin. RESULTS: In a 3700-m-equivalent environment, SpO2
      was reduced only when CPR was performed without breaths (P < .05, one-way
      analysis of variance (ANOVA) post hoc Tukey test). Heart rate increased during
      CPR regardless of the presence or absence of breaths. Mean scores on the Borg
      scale, a subjective measure of fatigue, after CPR action in the 3700-m-equivalent
      environment were significantly higher (15 +/- 2) than scores after CPR performed
      at sea level (11 +/- 2, P < .01, paired t-test). No lethal dysrhythmia was found
      in subjects with a wearable electrode shirt. CONCLUSIONS: Prolonged CPR at high
      altitude exerts a significant physical effect upon the condition of rescuers.
      Compression-only CPR at high altitude may deteriorate rescuer oxygenation,
      whereas CPR with breaths might ameliorate such deterioration.

PMID- 29352678
TI  - E-Bike-Related Trauma in Children and Adults.
AB  - BACKGROUND: Electric bike (e-bike) usage is growing worldwide, and so is the e
      bike-related injury rate. OBJECTIVE: This study was undertaken to characterize e
      bike-related injuries. METHODS: Data of all e-bike-related injuries presenting to
      our level I trauma center between 2014 and 2016 were collected and analyzed.
      Adult and pediatric (<18 years of age) e-bike-related injuries were then analyzed
      separately and compared. RESULTS: Forty-eight patients suffering from e-bike
      related injuries presented to our trauma center between January 1, 2014 and
      December 31, 2016. Seventeen (35%) patients were <18 years of age and 40 (85%)
      were male. The overall most common mechanism of injury was falling off the e-bike
      in 24 patients (50%), followed by collision with a static object in 9 patients
      (18.8%). Head (38%) and facial (33%) injuries were most common in children. In
      adult patients, orthopedic trauma was predominant, with extremity fractures in 35
      (73%) followed by significant lacerations in 14 patients (29%). Severe trauma
      (Injury Severity Score >15) was found in 17 (35%) patients. The duration of
      hospital stay was 10.8 +/- 6 days, 12 patients (25%) required a stay in the
      intensive care unit, and 21 patients (43.7%) required surgery. Compared to
      adults, children (<18 years of age) had significantly more head and face injuries
      (p = 0.05). CONCLUSION: Our study suggests that e-bike-related trauma may involve
      serious injuries and have typical injury patterns that resemble those seen in
      motorcycle-related injuries. Children are more likely to suffer head and face
      injuries because of their higher head to body ratio. We suggest that these
      injuries should therefore be triaged appropriately, preferably to a medical
      facility with proper trauma capabilities.

PMID- 29352680
TI  - Correction to Lancet Glob Health 2018; 6: e180-92.

PMID- 29352679
TI  - Inter-sexual habitat and isotopic niche segregation of the endangered Monteiro's
      storm-petrel during breeding.
AB  - At-sea distribution and trophic ecology of small seabird species (i.e.<100 g) is
      far less known when compared to their larger relatives. We studied the habitat
      use (spatial ecology) and isotopic niches (trophic ecology) of the endangered
      Monteiro's storm-petrel Hydrobates monteiroi during the incubation and chick
      rearing periods of 2013. There was a sexual foraging segregation of Monteiro's
      storm-petrels during the breeding period (tracking data) but also during the non
      breeding stage (stable isotope analysis). Females took advantage of their longer
      wings to forage over the shallower Mid-Atlantic ridge (MAR) north of Azores,
      under colder and windier regimes when compared to males, who mostly exploited
      northern deep waters comparatively closer to the breeding colony. Between-sex
      differences in the spatial distribution were more obvious during the incubation
      period, with the overlap in their distribution increasing during the chick
      rearing phase. There was also an isotopic segregation between sexes both during
      the previous breeding and the non-breeding stages, with females exhibiting a
      narrower, lower level isotopic niche when compared to males. Though the
      distribution patterns reported here should be useful for the at-sea conservation
      of this endangered species, future research should focus on (1) performing year
      round tracking to map the species' distribution during the non-breeding period
      and (2) gathering multi-year tracking information to understand the effect of
      inter-annual environmental stochasticity on the foraging choices and trophic
      habits of the species.

PMID- 29352681
TI  - No Consensus for Femoral Head Impaction Technique in Surgeon Education Materials
      From Orthopedic Implant Manufacturers.
AB  - BACKGROUND: Prior studies indicate that one factor that may contribute to total
      hip arthroplasty failure due to mechanically assisted crevice corrosion at the
      femoral head-trunnion junction is the method of femoral head fixation. METHODS:
      Up-to-date on-line surgical technique guides describing fixation of the
      prosthetic femoral head of common implants of the 4 largest manufacturers as well
      as 2 minor manufacturers were identified. The information given regarding
      preparation and fixation of the femoral head was evaluated and compared. RESULTS:
      A total of 24 surgical technique guides were evaluated. Most guides (22/24)
      addressed fixation technique; of these, 19 of 22 suggested cleaning and 20 of 22
      suggested drying the trunnion prior to affixing the femoral head. The manner of
      fixation, however, varied widely and there was no single technique advocated.
      CONCLUSION: The majority of surgeon education materials do not specify a single
      technique for assembly of the head femoral component in total hip arthroplasty.
      If the method of fixation is indeed important, efforts should be made to identify
      the best technique, and improve and unify the surgical technique instructions.

PMID- 29352682
TI  - Are Allogeneic Transfusions Decreasing in Total Knee Arthroplasty Patients?
      National Inpatient Sample 2009-2013.
AB  - BACKGROUND: Allogeneic transfusions are commonly used for substantial blood loss
      in total knee arthroplasty (TKA), but have been associated with adverse effects
      and increased costs. The purpose of this study is to provide a detailed
      description of (1) trends of allogeneic blood transfusion; (2) risk factors and
      adverse events; and (3) discharge disposition, length-of-stay (LOS), and
      cost/charge analysis for primary TKA patients who received an allogeneic blood
      transfusion from 2009-2013. METHODS: A cohort of 3,217,056 primary TKA patients
      was identified from the National Inpatient Sample database from 2009-2013.
      Demographic, clinical, economic, and discharge data were analyzed for patients
      who received allogeneic blood products, and for those who did not receive any
      type of blood transfusion. Other parameters analyzed include risk factors,
      adverse events, discharge disposition, and costs/charges. RESULTS: There was a
      significant decline in use of allogeneic transfusion from 2009-2013 incidence
      (13.9%-7.3%; P < .001). All comorbidities examined were associated with
      significantly increased risk of receiving allogeneic transfusion with exception
      of patients with AIDS, metastatic cancer, and peptic ulcer disease. Allogeneic
      transfusion was associated with worse outcomes during hospitalization. Patients
      also had a greater likelihood of discharge to short-term care, greater LOS, and
      greater median costs/charges. Among TKA patients who received an allogeneic
      transfusion, costs varied based on hospital ownership and characteristics,
      primary-payer, region, and bed-size. CONCLUSION: Given the poor outcomes and
      higher costs associated with allogeneic transfusions, efforts must be undertaken
      to minimize this risky practice. With the projected increase in demand for TKAs,
      orthopedists must understand effective blood management strategies.

PMID- 29352683
TI  - Discharge to Inpatient Rehab Does Not Result in Improved Functional Outcomes
      Following Primary Total Knee Arthroplasty.
AB  - BACKGROUND: Monitored rehabilitation has long been considered an essential part
      of the recovery process in total knee arthroplasty (TKA). However, the optimal
      setting for rehabilitation remains uncertain. We sought to determine whether
      inpatient rehabilitation settings result in improved functional and patient
      reported outcomes after primary TKA. METHODS: All patients undergoing primary TKA
      from May 2007 to February 2011 were identified from our institutional total joint
      registry. Propensity score matching was then performed, resulting in a final
      cohort of 1213 matched pairs for discharge destination to either home or a
      rehabilitation facility (inpatient rehab or skilled nursing facility). Length of
      stay, need for manipulation, 6-month complications, and 2-year Western Ontario
      and McMaster Universities Osteoarthritis Index, Lower Extremity Activity Scale,
      12-item Short Form Health Survey, and Hospital for Special Surgery knee
      expectations surveys were compared. RESULTS: Patients discharged to a rehab
      facility were noted to have a shorter hospital length of stay (5.0 vs 5.4 days).
      Patients discharged to inpatient rehabilitation reported more fractures at 6
      months postoperatively. However, no differences in manipulation rates, 2-year
      outcome scores, or changes in outcome scores were found between the 2 groups.
      CONCLUSION: Inpatient rehabilitation settings did not result in lower
      complications at 6 months or improved functional or patient-reported outcomes at
      2 years compared to discharge directly to home when patients are propensity
      matched for age, living situation, comorbidities, baseline functional status, and
      insurance status. This finding has important cost implications and calls into
      question whether the healthcare system should allow otherwise healthy patients to
      use inpatient rehabilitation services postoperatively after primary TKA.

PMID- 29352684
TI  - Long-Term Outcome of Hip Arthroplasty in the Setting of Pigmented Villonodular
      Synovitis.
AB  - BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare, benign, painful
      proliferation of the synovium previously treated successfully with total hip
      arthroplasty (THA). Published results come from small series; therefore, the
      purpose of this study is to investigate the outcomes of THA in the setting of
      PVNS. METHODS: We identified 25 patients with histologically confirmed, diffuse
      PVNS who underwent THA between 1971 and 2013. Mean follow-up and age was 10 years
      and 39 years. Before arthroplasty, 16 patients (64%) had at least 1 surgical
      procedure (mean, 1; range, 1-3) to treat PVNS. Twenty (80%) patients had "active"
      disease and underwent synovectomy. No constrained acetabular components were
      used. RESULTS: The 10-year disease free-survival was 100%. Recurrence occurred in
      1 patient at 24 years postoperatively. Nineteen patients (76%) sustained a
      complication (most commonly component loosening (n = 12 [48%]), and 16 required
      revision surgery. The 10-year revision-free survival was 66% for conventional
      polyethylene implants and 100% for highly cross-linked polyethylene devices. Mean
      Harris Hip Score improved significantly from 48 (range, 23-69) preoperatively to
      78 (range, 47-96) postoperatively (P < .001). CONCLUSION: THA in the setting of
      PVNS improves patient function with a low rate of local recurrence. Complication
      and revision rates are high in this series likely owing to the young and active
      patient population and the use of conventional polyethylene. Modern bearings
      theoretically reduce the risk of revision.

PMID- 29352685
TI  - Factors Associated With Posterior Cruciate Ligament Tightness During Cruciate
      Retaining Total Knee Arthroplasty.
AB  - BACKGROUND: The purpose of our study was to identify factors affecting posterior
      cruciate ligament (PCL) tightness during cruciate-retaining total knee
      arthroplasty. METHODS: A total of 225 varus osteoarthritic knees that underwent
      cruciate-retaining total knee arthroplasty were included in this study. When the
      flexion gap was tighter than the extension gap after all bone resection and the
      lift-off sign was positive during surgery, the PCL was released. The association
      between PCL release and potential risk factors, such as age, gender, body mass
      index, preoperative range of motion, anterior cruciate ligament status,
      preoperative hip-knee-ankle angle (HKA), decrease in posterior condylar offset,
      and also change in tibial posterior slope angle (TPSA) from preoperative to
      postoperative measurement, was evaluated by univariate and multivariate logistic
      regression analyses. RESULTS: The PCL was released in 68 of 225 knees (30.2%).
      According to the univariate logistic regression analysis, preoperative knee
      flexion angle (odds ratio [OR], 0.98), anterior cruciate ligament status (OR,
      3.94), the decrease in medial (OR, 0.73) and lateral posterior condylar offset
      (OR, 0.76), preoperative HKA (OR, 1.1), preoperative (OR, 1.15) and postoperative
      TPSA (OR, 0.77), and the decrease in TPSA (OR, 1.23) were associated with PCL
      release. Multivariable stepwise logistic regression analysis demonstrated that
      preoperative HKA (P < .001), postoperative TPSA (P = .02), and the decrease in
      TPSA (P < .001) were independently associated with PCL release. CONCLUSION: Many
      factors are associated with PCL tightness. The change in TPSA between
      preoperative and postoperative measurements was a higher risk factor than
      postoperative TPSA.

PMID- 29352686
TI  - Interobserver and Intraobserver Reliability of Computed Tomography-Based Three
      Dimensional Preoperative Planning for Primary Total Knee Arthroplasty.
AB  - BACKGROUND: Preoperative planning is an important factor for total knee
      arthroplasty (TKA). The aim of this study is to document the interobserver and
      intraobserver reliability of computed tomography (CT)-based 3-dimensional (3D)
      preoperative planning for primary TKA. METHODS: Twenty knees (10 with
      osteoarthritis and 10 with rheumatoid arthritis) were studied independently by 6
      orthopedic surgeons using a CT-based 3D planning system. The measurements were
      made twice at more than 3-week intervals without any knowledge of their own
      previous measurements or those of the others. We assessed the femoral and tibial
      component sizes and the alignment of the femoral component. RESULTS: The
      interobserver and intraobserver agreements for femoral component size were 44.3%
      and 62.5% with exact size, and increased to 90.7% and 99.2% within one size
      difference; the intraclass correlation coefficients (ICCs) were 0.919 and 0.936,
      respectively. The interobserver and intraobserver agreements for tibial component
      size were 57.0% and 66.7% with exact size, and increased to 87.3% and 90.0%
      within one size difference; the ICCs were 0.909 and 0.924, respectively. The ICCs
      for femoral and tibial size were better in rheumatoid arthritis than in
      osteoarthritis. Interobserver ICC for femoral valgus angle was 0.807, and 0.893
      for intraobserver reliability. Interobserver ICC of the femoral external rotation
      angle was 0.463, and 0.622 for intraobserver reliability. CONCLUSION: CT-based 3D
      preoperative planning for primary TKA has clinical implications for predicting
      appropriate size and alignment of the component in patients with osteoarthritis
      and rheumatoid arthritis.

PMID- 29352687
TI  - What Influence Does the Time of Year Have on Postoperative Complications
      Following Total Knee Arthroplasty?
AB  - BACKGROUND: The time of year might influence the occurrence of surgical
      complications. Therefore, this study investigated correlations between the time
      of-year and 30-day postoperative complication rates following primary total knee
      arthroplasty (TKA). Specifically, we determined (1) postoperative complication
      rates across all quarters; and (2) time-of-year influence on complications using
      univariate and multivariate regression analyses. METHODS: CPT code 27447
      identified 147,473 TKAs from the NSQIP database. Readmissions, reoperations, as
      well as medical and surgical complications occurring within 30 postoperative days
      were assessed. All TKAs were divided into 4 cohorts based on the quarter-of-the
      year (Q1-Q4) during which the surgery was performed. Chi-Square, ANOVA, linear
      regression, as well as univariate and multivariate analyses were performed to
      compare complication rates. A P < .05 was set for statistical significance.
      RESULTS: Q3 had a higher risk of superficial infection when compared to Q1 (OR
      1.37; 95% CI 1.12-1.69; P = .002). There was a lower risk of pneumonia between Q2
      and Q1 (OR: 0.7; 95% CI 0.54-0.90; P = .007) as well as Q4 and Q1 (OR 0.76; 95%
      CI 0.6-0.96; P = .017). Blood transfusion was lower in Q2, Q3, and Q4 compared to
      Q1 (P = .02, P < .001, and P < .001). CONCLUSION: This study provides a baseline
      analysis correlating the time of year and outcomes of TKA. However, since
      seasonality and weather can vary greatly in the United States by geographic
      region and time of year, future studies should be performed at a more granular
      level using hospital-specific data correlating weather and region to TKA
      outcomes.

PMID- 29352689
TI  - Morbidity and Safety of Iliac Crest Reference Array Pins in Navigated Total Hip
      Arthroplasty: A Prospective Cohort Study.
AB  - BACKGROUND: Navigated total hip arthroplasty (THA) can employ intra-osseous pins
      through a separate incision to secure reference arrays to the iliac crest. This
      study is the first to investigate the consequences of pin use in THA in vivo.
      METHODS: A prospective, consecutive series of 43 patients presenting for
      navigated THA were included. Two temporary 125 * 4 mm Schanz screws were inserted
      into the iliac crest for the attachment of a reference array. Telephone follow-up
      occurred at 6 and 12 weeks post-operatively. Patients were asked about pain,
      interference with daily activities, how often the wound was noticed, and duration
      of discomfort. Patient body mass index was recorded. RESULTS: The follow-up rate
      was 100%. Pin site pain at any time post-operatively was reported by 24 patients
      (56%). This improved to 30%, 9%, and 2% at 3, 6, and 12 weeks, respectively. On
      average, pain lasted for 16 days total. The most common complaints after pain
      were clothing discomfort (23%), pain when wearing a belt (12%), or pain when
      mobilizing (9%). For the majority (98%) of patients, all symptoms had resolved by
      12 weeks. There was no nerve injury, pin site fracture, infection, or screw
      breakage. Patients with body mass index greater than 30 kg/m2 were up to 3 times
      more likely to experience pin site pain (P = .05), and had a longer duration of
      pain (P = .04). CONCLUSION: Surgeons and patients should be aware that using
      navigational pins for array fixation carries low complication rates but often
      will cause pain and irritation that resolves in the short term.

PMID- 29352688
TI  - The Association Between Readmission and Patient Experience in a Total Hip
      Arthroplasty Population.
AB  - BACKGROUND: Our goal was to determine whether readmissions within 30 or 90 days
      following discharge are associated with Hospital Consumer Assessment of
      Healthcare Providers and Systems (HCAHPS) scores for total hip arthroplasty (THA)
      patients. METHODS: HCAHPS surveys from all patients who underwent THA between
      January 2016 and September 2016 in our institution were analyzed. Readmissions,
      demographics, baseline joint pain, joint function, and Veterans RAND-12 scores
      were collected. Statistical analyses involved Pearson's chi-squared tests for
      categorical variables and Student's t-tests for continuous variables.
      Multivariable logistic regression models were used to determine whether 30-day or
      90-day readmissions were independently associated with HCAHPS scores. RESULTS: A
      total of 1868 patients were identified, the survey was sent to 969 patients and
      578 completed the survey (59.6%). Eight patients (1.4%) were readmitted within 30
      days, and 28 patients (4.8%) within 90 days. These patients were more likely to
      undergo revision THA (P < .001). For the 30-day readmission cohort, 4 of 8
      patients (50.0%) rated the hospital a 9 or 10 out of 10 compared to 466 of 567
      patients (82.2%) of the non-readmitted cohort (P = .019). Thirty-day readmissions
      were associated with significantly lower likelihood of rating the hospital a 9 or
      10 out of 10 (odds ratio 0.18). CONCLUSIONS: Our results demonstrate a
      significant negative association between readmission and HCAHPS scores under
      several dimensions of the survey including nurse communication, doctor
      communication, pain management, and global satisfaction with the hospital
      experience.

PMID- 29352690
TI  - Diagnostic Utility of Histological Analysis for Detecting Ongoing Infection
      During Two-Stage Revision Arthroplasty in Patients With Inflammatory Arthritis.
AB  - BACKGROUND: Surgeons often rely on intra-operative histology (frozen sections
      [FS]) to determine the next step in surgical management during the second stage
      (re-implantation surgery) of 2-stage revision arthroplasty. The purpose of the
      study is to assess the accuracy of permanent sections (PS) and FS in the
      diagnosis of persistent infection during re-implantation in patients with an
      inflammatory arthritis. METHODS: From 2001 to 2016, 47 planned second-stage
      revision total hip arthroplasty and total knee arthroplasty in patients with
      inflammatory arthritis were identified. Revisions were classified as having
      persistent infection if they were Musculoskeletal Infection Society positive at
      the time of second stage. PS or FS was considered to be positive for infection
      when at least one of the specimens demonstrated an acute inflammation. Receiver
      operating characteristic analysis was performed to obtain the diagnostic
      parameters. RESULTS: There were 9 (19%) persistent infections. Both PS and FS had
      very high specificity (PS = FS = 94.7%). Sensitivity of PS was higher than FS,
      although not statistically significant (PS = 88.9%, FS = 55.6%, P = .083).
      Overall, PS had a better diagnostic utility than FS (area under the curve: PS vs
      FS = 0.92 vs 0.75, P = .045). Four specimens had discrepancies between PS and FS
      histology. In all 4 instances, the specimens were read as positive (infected) by
      PS, but negative by FS. CONCLUSION: Histological analysis is recommended at the
      time of re-implantation surgery even in patients with inflammatory arthritis. PS
      had a better diagnostic utility than FS suggesting that areas of acute
      inflammation may be scattered and may not always be captured in the specimens
      taken for FS.

PMID- 29352691
TI  - Adopting an early invasive strategy for non-ST-elevation myocardial infarction:
      Analysis of the Portuguese Registry on Acute Coronary Syndromes.
AB  - INTRODUCTION: In patients with non-ST-elevation myocardial infarction (NSTEMI),
      the best timing for coronary angiography is not definitely established, although
      it is recognized that in high-risk patients it should be performed within the
      first 24 hours. The aim of this work was to describe the evolution over time of
      the use of an invasive strategy in the treatment of NSTEMI and in-hospital
      mortality. METHODS: We performed a retrospective analysis of patients admitted
      with NSTEMI included in the Portuguese Registry on Acute Coronary Syndromes
      (ProACS) between 2002 and 2015. The annual proportion of patients undergoing
      coronary angiography and the time from admission to coronary angiography were
      assessed, as were changes in mortality and length of stay. RESULTS: A total of 18
      639 patients with NSTEMI were included in the ProACS registry between 2002 and
      2015. Over this period there were significant increases in the proportion of
      patients undergoing coronary angiography (from 52.0 to 83.6%) and angioplasty
      (from 23.3 to 53.0%), as well as in the proportion of patients who underwent
      coronary angiography within 24 hours of admission (from 21.0 to 48.1%). In
      hospital mortality decreased in those aged over 74 years (from 9.5 to 3.7%) and
      in males. CONCLUSIONS: The progressive adoption of an invasive strategy,
      particularly an early one (within 24 hours), was accompanied by a reduction in in
      hospital mortality. Since coronary angiography is performed late (>24 hours) in
      half of NSTEMI patients, these patients could benefit from initiatives similar to
      Stent for Life.

PMID- 29352692
TI  - CKD-EPI versus Cockcroft-Gault formula for predicting contrast-induced
      nephropathy following percutaneous coronary intervention in patients without
      significant renal impairment.
AB  - INTRODUCTION: Individuals with glomerular filtration rate (GFR) >=60 ml/min/1.73
      m2 estimated by the Cockcroft-Gault formula (CG) who undergo percutaneous
      coronary intervention (PCI) frequently develop contrast-induced nephropathy
      (CIN). This study aimed to assess whether individuals with significant renal
      impairment assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD
      EPI) formula, but not by CG, more often develop CIN following PCI than those
      without renal impairment by either formula. METHODS: In this cross-sectional
      study analyzing patients with baseline CG GFR >=60 ml/min/1.73 m2 before PCI,
      subjects were divided into two groups according to CIN occurrence. Baseline CKD
      EPI GFR was calculated for all patients. RESULTS: We analyzed 140 patients.
      Baseline GFR was 87.5+/-21.3 and 77.1+/-15.0 ml/min/1.73 m2 for CG and CKD-EPI,
      respectively. CIN occurred in 84.6% of individuals with baseline CKD-EPI GFR <60
      ml/min/1.73 m2 vs. 51.1% of those without. Males and those with higher body mass
      index were more likely to present baseline CKD-EPI GFR <60 ml/min/1.73 m2
      (p=0.021). Non-ionic contrast agent use and baseline CKD-EPI GFR >=60 ml/min/1.73
      m2 were protective factors against CIN. Greater amounts of contrast agent and
      acute coronary syndrome were associated with higher CIN risk. In subjects with
      serum creatinine <1.0 mg/dl, GFR was more likely to be overestimated by CG, but
      not by CKD-EPI (sensitivity 100.0%; specificity 52.0%). CONCLUSION: In patients
      undergoing PCI without renal dysfunction by CG, a finding of CKD-EPI GFR <60 ml/
      min/1.73 m2 was associated with a higher probability of CIN, especially among men
      and those with higher body mass index.

PMID- 29352693
TI  - The association between estimated glomerular filtration rate, albuminuria, and
      risk of cardiovascular hospitalizations and all-cause mortality among patients
      with type 2 diabetes.
AB  - AIMS: We evaluated the simultaneous effects of all clinically recognized
      categories of albuminuria and estimated glomerular filtration rate (eGFR) on
      cardiovascular disease (CVD) and mortality METHODS: We conducted a longitudinal
      observational study of 16,678 type 2 diabetes (T2D) patients. From the first
      serum creatinine value from 2006 to 2012 and a urine-albumin creatinine ratio
      (UACR) recorded within 6months, we applied baseline Kidney Disease: Improving
      Global Outcomes (KDIGO) categories of eGFR and albuminuria. We followed patients
      for up to 11years to calculate adjusted incidence per 1000person-years (p-y) of
      first CVD hospitalization and all-cause mortality. RESULTS: Over 98,069p-y of
      follow-up, CVD hospitalization risk was greater for each higher eGFR and
      albuminuria category. In eGFR category G2 (60-89mL/min/1.73m2), adjusted
      incidence per 1000p-y was 14.1 (95% CI 12.9-15.5), 19.8 (17.2-22.8), and 22.8
      (17.4-30.0) for normoalbuminuria, microalbuminuria and macroalbuminuria,
      respectively. For eGFR category G3a (45-59), rates were 26.7 (22.3-32.0), 40.3
      (32.2-50.5), and 44.1 (28.8-67.4), respectively. Adjusted risk of all-cause
      mortality followed a similar pattern. CONCLUSIONS: Our data underscore the
      importance of including detailed eGFR and UACR values in assessing CVD risk. High
      albuminuria and low eGFR is a potent predictor of CVD and death.

PMID- 29352694
TI  - Age, age at diagnosis and diabetes duration are all associated with vascular
      complications in type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes (T2DM) is increasingly diagnosed in younger patients.
      The trajectory of complications in patients diagnosed at a younger or older age
      is not well understood. We examine the associations between age, age at diagnosis
      and diabetes duration and vascular complications in patients with T2DM. METHODS:
      A cross-sectional study of pre-specified demographic and clinical data, from 3419
      adults with T2DM participating in the Australian National Diabetes Audit (2015).
      Factors associated with diabetes complications were analysed using logistic
      regression. RESULTS: Mean (+/-SD) current age was 62.9+/-12.5years, age at
      diagnosis was 49.4+/-12.3years and mean diabetes duration was 13.5+/-9.4years.
      Macrovascular complications were more prevalent in patients who were older at
      diabetes diagnosis whereas microvascular complications were more prevalent in
      patients who were younger at diabetes diagnosis. Age, age at diagnosis and
      diabetes duration were all independently associated with increased risk of
      macrovascular complications after adjustment for sex, smoking, BMI and
      microvascular complications (all p<0.001). In contrast, only diabetes duration
      was independently associated with microvascular complications after adjustment
      for sex, smoking, BMI and macrovascular complications (p<0.001). CONCLUSIONS:
      Age, age at diagnosis, and diabetes duration were all independently associated
      with macrovascular complications whereas only diabetes duration was independently
      associated with microvascular complications.

PMID- 29352695
TI  - Truly anatomic coracoclavicular ligament reconstruction with 2 Endobutton devices
      for acute Rockwood type V acromioclavicular joint dislocations.
AB  - BACKGROUND: Truly anatomic coracoclavicular ligament reconstruction (TACCR)
      according to the original insertions is a creative new method for the treatment
      of severe acromioclavicular separation. This research analyzed the clinical and
      radiologic results of TACCR in 25 patients with at least 2-year follow-up.
      METHODS: The study enrolled 25 patients with Rockwood type V acromioclavicular
      joint dislocations who underwent TACCR using 2 Endobutton (Smith & Nephew Inc.,
      Andover, MA, USA) devices from May 2013 to October 2015. Patients were assessed
      with clinical and radiologic follow-up at 3, 6, 12, 18, and 24 months
      postoperatively. The clinical assessments consisted of the visual analog scale
      and the Constant score. The radiographic evaluations were performed by
      measurements of the coracoclavicular distance. RESULTS: The mean follow-up was 34
      +/- 6.8 months (range, 24-48 months). The visual analog scale and Constant scores
      revealed significant advancements from 5 +/- 0.9 (range, 4-7) and 45 +/- 5.6
      (range, 30-54) scores preoperatively to 0 +/- 0.5 (range, 0-2) and 95 +/- 2.9
      (range, 91-98) scores at 24 months postoperatively, respectively. The
      coracoclavicular distance significantly decreased from 23 +/- 5.4 mm (range, 16
      34 mm) preoperatively to 8 +/- 0.9 mm (range, 7-10 mm) at the final follow-up.
      CONCLUSIONS: TACCR represents a safe, reliable and creative surgical technique
      that yields good to excellent clinical and radiologic outcomes in the treatment
      of severe acromioclavicular separation.

PMID- 29352696
TI  - Safety and Efficacy of Prostatic Artery Chemoembolization for Prostate Cancer
      Initial Experience.
AB  - PURPOSE: To evaluate outcome of prostatic artery chemoembolization for patients
      with prostate cancer (PCa). MATERIALS AND METHODS: This single-center prospective
      cohort study was conducted between August 2013 and July 2016 in 20 patients with
      PCa who underwent chemoembolization. Mean patient age was 67.5 years +/- 6.4.
      Gleason score was 6-10, and staging was T2N0M0. Fifteen patients refused
      prostatectomy and 5 wanted to stop hormonal therapy because of side effects. For
      chemoembolization, Chelidonium majus mother tincture 1 mL was slowly injected
      into the prostatic arteries. Docetaxel 1 mL and 150-300 MUm Embosphere (Merit
      Medical Systems, Inc, South Jordan, Utah) microspheres 0.5 mL were thoroughly
      mixed, and the mixture was slowly injected by the same route. Embolization of
      prostatic arteries was finished with 150-300 MUm Embosphere microspheres.
      Technical success was defined as bilateral prostatic artery embolization.
      Biochemical failure was defined as prostate specific antigen (PSA) decrease to <
      2 ng/mL followed by recurrence when PSA increased to > 2 ng/mL within 1 month
      after success. RESULTS: Technical success was 80.0% (16/20 patients). Biochemical
      failure was 18.7% (3/16 patients). There was 1 short-term biochemical recurrence
      at 4 months and 2 midterm recurrences (12-18 months). Biochemical success at 12
      18 months was 62.5% (10/16 patients). Adverse events (31.3%) included a small
      area (2 cm2) of bladder wall ischemia, which was removed by surgery (n = 1);
      transient acute urinary retention (n = 1) and urinary urgency (n = 1) for 1 week;
      sexual dysfunction (n = 2), which completely recovered after 10 and 12 months,
      respectively. CONCLUSIONS: Prostatic artery chemoembolization allowed a
      biochemical response in patients with localized PCa and is a promising treatment.

PMID- 29352697
TI  - Venous Ports in Infants.
AB  - PURPOSE: To evaluate technical success and the incidences of, and risk factors
      for, mechanical and infectious complications of venous port placement in infants.
      MATERIALS AND METHODS: This was a retrospective single-institution cohort study
      of port placement in infants (age < 1 y) from January 2006 through June 2016
      (mean age, 7.5 mo +/- 3.3; mean weight, 8.1 kg +/- 1.9). Age, weight, sex, side
      of placement, tip position, and indication for placement (chemotherapy vs other)
      were recorded. Total catheter-days (CDs), mechanical complications, and central
      catheter-associated bloodstream infections (CCABSIs) were identified. RESULTS:
      During the study years, 64 ports were placed in 64 infants, with a technical
      success rate of 100%. The mean catheter life was 321 days (total range, 4-1,917
      d; interquartile range [IQR], 107-421 d). There were 13 CCABSI events (0.63 per
      1,000 CDs); of these, 8 (12.5% among 64 patients) required port removal for
      infection. There was an increase in CCABSIs in patients with left-sided port
      placement (relative risk [RR], 3.22; 95% confidence interval [CI], 1.02-10.14; P
      = .05). There were 8 mechanical complications of the port reservoir or catheter
      (0.39 per 1,000 CDs). Of these, 2 (3.1%) required removal. Patients in the lowest
      weight quartile were at an increased risk of mechanical complications (RR, 4.37;
      95% CI, 1.09-17.48; P = .04). CONCLUSIONS: Venous ports can be placed with a high
      rate of technical success in infants. Left-sided ports and low weight are
      associated with increased infectious and mechanical complications, respectively.

PMID- 29352698
TI  - Gastric Varices Bleed at Lower Portosystemic Pressure Gradients than Esophageal
      Varices.
AB  - PURPOSE: To quantify and compare portosystemic pressure gradients (PSGs) between
      bleeding esophageal varices (EV) and gastric varices (GV). MATERIALS AND METHODS:
      In a single-center, retrospective study, 149 patients with variceal bleeding (90
      men, 59 women, mean age 52 y) with EV (n = 69; 46%) or GV (n = 80; 54%) were
      selected from 320 consecutive patients who underwent successful transjugular
      intrahepatic portosystemic shunt (TIPS) creation from 1998 to 2016. GV were
      subcategorized using the Sarin classification as gastroesophageal varices (GEV)
      (n = 57) or isolated gastric varices (IGV) (n = 23). PSG before TIPS was measured
      from the main portal vein to the right atrium. PSGs were compared across EV, GEV,
      and IGV groups using 1-way analysis of variance. RESULTS: Overall mean baseline
      PSG was 21 mm Hg +/- 6. PSG was significantly higher in patients with EV versus
      GV (23 mm Hg vs 19 mm Hg; P < .001). Mean PSG was highest among EV (23 mm Hg)
      with lower PSGs identified for GEV (20 mm Hg) and IGV (16 mm Hg); this difference
      was statistically significant (P < .001). Among 95 acute bleeding cases, a
      similar pattern was evident (EV 23 mm Hg vs GEV mm Hg 20 vs IGV 17 mm Hg; P <
      .001). At baseline PSG < 12 mm Hg, 13% (3/23) of IGV bled versus 9% (5/57) of GEV
      and 3% (2/69) of EVs (P = .169). Mean final PSG after TIPS was 8 mm Hg (IGV 6 mm
      Hg vs EV and GEV 8 mm Hg; P = .005). CONCLUSIONS: GV bleed at lower PSGs than EV.
      EV, GEV, and IGV bleeding is associated with successively lower PSGs. These
      findings highlight distinct physiology, anatomy, and behavior of GV compared with
      EV.

PMID- 29352699
TI  - Computed tomography (CT) assessment of the membranous septal anatomy prior to
      transcatheter aortic valve replacement (TAVR) with the balloon-expandable SAPIEN
      3 valve.
AB  - OBJECTIVES: The lower limit of the membranous septum (MS) is considered an
      anatomic landmark for the emergence of the Bundle of His into the left ventricle.
      Computed tomography (CT) assessment of MS anatomy may provide useful information
      about the risk of conduction abnormalities following transcatheter aortic valve
      replacement (TAVR). METHODS AND RESULTS: The study included 102 consecutive
      patients undergoing TAVR with the Edwards Sapien 3 (S3) valve. Using pre-TAVR CT
      and post-procedure angiography we evaluated for the presence of calcium in the
      left ventricular outflow tract (LVOT), calcium depth (CD), implantation depth
      (ID) and MS length. The MS length minus the prosthesis ID was calculated (Delta
      MSID). Outcomes included new left bundle branch block (LBBB) or permanent
      pacemaker (PPM) within 30days. Seventeen patients (17%) received a PPM and 28
      (27%) developed new LBBB following TAVR. Mean (+/-SD) MS length and delta MSID
      were 7.5mm (2) and 0.9mm (4.5), respectively. Twenty-one patients (20%) had
      calcium in the device landing zone and the mean (SD) CD was 6.8mm (+/-4). Calcium
      in the device landing zone (37% versus 16%, p=0.02) and implantation depth (6mm
      (4-8) versus 4mm (4-5), p=0.02) predicted new conduction abnormalities after
      TAVR. CONCLUSIONS: The presence of calcium in the device landing zone is
      associated with increased risk of conduction abnormalities after TAVR with S3. In
      such cases, a more aortic deployment of the prosthesis may be warranted.

PMID- 29352700
TI  - High sensitivity troponin in the management of tachyarrhythmias.
AB  - BACKGROUND: The introduction of the highly sensitive troponin (hs-trop) assays
      into clinical practice has allowed for the more rapid diagnosis or exclusion of
      type 1 myocardial infarctions (T1MI) by clinicians, in addition type 2 myocardial
      infarctions (T2MI) are now more frequently detected. Tachyarrhythmias are one of
      the common causes of T2MI, the medium and long term outcome for this cohort of
      T2MI is yet to be clarified. METHODS: Retrospective review of consecutive
      patients admitted with a diagnosis of either (a) non ST-elevation myocardial
      infarction (NSTEMI) or (b) tachyarrhythmia was performed. Data were collected on
      patient demographics and investigations. Patient mortality status was recorded
      through the Personal Demographics Service (PDS) via NHS Digital. RESULTS: A total
      of 704 patients were eligible for inclusion to the study. 264 patients were
      included in the study with a final discharge diagnosis of NSTEMI and 440 patients
      with a final discharge diagnosis of tachyarrhythmia. There was a significantly
      higher peak troponin in NSTEMI patients compared to the tachyarrhythmia troponin
      positive group (4552ng/L vs 571ng/L, p<0.001). Mortality was significantly higher
      in the troponin positive tachyarrhythmia patients than the troponin negative
      patients (54 vs 34, 26.2% vs 14.5%, log rank p=0.003), furthermore, the mortality
      of NSTEMI and troponin positive tachyarrhythmia patients was similar (55 vs 54,
      20.8% vs 26.2%, log rank p=0.416). Only one patient (0.14%) was given a formal
      diagnosis of T2MI. CONCLUSIONS: These data suggest that troponin positive
      tachyarrhythmia is not a benign diagnosis, and has a mortality rate similar to
      NSTEMI. Formal labeling as T2MI is rare in real life practice. More investigation
      into the detection and management of T2MI and troponin positive arrhythmia
      patients is now warranted.

PMID- 29352701
TI  - Bailout surgical explantation of a transcatheter valve-in-valve for subacute
      thrombosis: When there is no time for anticoagulation: Case report and literature
      review.
AB  - Trancatheter heart valve (THV) thrombosis is effectively treated with
      anticoagulation but alternative therapies are required when a faster gradient
      reduction is needed. Open heart surgery has been rarely performed due to the high
      perioperative mortality and only five cases have been described so far. Here we
      describe a case of emergent surgical explantation for THV thrombosis after a
      valve-in-valve. A 67years old man underwent transcatheter aortic valve
      implantation for a failed surgical bioprosthesis Epic 21mm (St. Jude Medical; St.
      Paul, Minnesota, US). A CoreValve 23mm (Medtronic, Minneapolis, Minnesota, US)
      was implanted through femoral access under conscious sedation without
      complications. Mean transvalvular gradient was effectively reduced (33mmHg vs
      16mmHg) with no more than mild residual aortic regurgitation. After 8days the
      patient was discharged on dual antiplatelet therapy but was readmitted to the
      intensive care unit for pulmonary oedema 13days later. Echocardiography showed a
      raised transvalvular mean gradient (mean gradient change from discharge=15mmHg)
      without aortic regurgitation. Heart Team decided for emergent open heart surgery
      for the hemodynamic instability. On direct inspection THV was well positioned
      inside the surgical bioprosthesis but two cusps were covered by thrombus which
      markedly restricted their mobility. The THV and the former surgical valve were
      explanted and a new larger stented bioprosthesis was implanted. Thrombosis of the
      THV was confirmed on microscopic examination which showed no signs of
      inflammation or degeneration. The patient was discharged after 1month and the
      3month follow up showed stable transvalvular gradients.

PMID- 29352702
TI  - Inotuzumab ozogamicin in older patients with acute lymphoblastic leukaemia:
      premises and promises.

PMID- 29352703
TI  - Inotuzumab ozogamicin in combination with low-intensity chemotherapy for older
      patients with Philadelphia chromosome-negative acute lymphoblastic leukaemia: a
      single-arm, phase 2 study.
AB  - BACKGROUND: Inotuzumab ozogamicin, an anti-CD22 monoclonal antibody bound to a
      toxin, calicheamicin, has shown single-agent activity in relapsed or refractory
      acute lymphoblastic leukaemia. We aimed to assess the activity and safety of
      inotuzumab ozogamicin in combination with low-intensity chemotherapy in older
      patients with acute lymphoblastic leukaemia. METHODS: We did a single-arm, phase
      2 study at the MD Anderson Cancer Center (Houston, TX, USA). Eligible patients
      were aged 60 years or older and had newly diagnosed, Philadelphia chromosome
      negative, acute lymphoblastic leukaemia, and an Eastern Cooperative Oncology
      Group performance status of 3 or lower. The induction chemotherapy regimen used
      was mini-hyper-CVD (a lower intensity version of the conventional hyper-CVAD).
      Odd-numbered cycles (1,3, 5, and 7) comprised intravenous cyclophosphamide (150
      mg/m2 every 12 h on days 1-3) and oral or intravenous dexamethasone (20 mg per
      day on days 1-4 and days 11-14); no anthracycline was administered. Intravenous
      vincristine (2 mg flat dose) was given on days 1 and 8. Even-numbered cycles
      comprised intravenous methotrexate (250 mg/m2 on day 1) and intravenous
      cytarabine (0.5 g/m2 given every 12 h on days 2 and 3). Intravenous inotuzumab
      ozogamicin was given on day 3 of the first four cycles at the dose of 1.3-1.8
      mg/m2 at cycle 1, followed by 1.0 -1.3 mg/m2 in subsequent cycles. Maintenance
      therapy with dose-reduced POMP (purinethol [6-mercaptopurine], oncovin
      [vincristine sulfate], methotrexate, and prednisone) was given for 3 years. The
      primary endpoint of this study was progression-free survival at 2 years. Analyses
      were by intention to treat. The study is ongoing, recruiting patients for an
      approved expansion phase with a modified treatment plan by protocol amendment.
      The trial is registered with ClinicalTrials.gov, number NCT01371630. FINDINGS:
      Between Nov 12, 2011, and April 22, 2017, 52 patients with a median age of 68
      years (IQR 64-72) were enrolled. With a median follow-up of 29 months (IQR 13
      48), 2-year progression-free survival was 59% (95% CI 43-72). The most frequent
      grade 3-4 adverse events were prolonged thrombocytopenia (42 [81%] patients),
      infections during induction (27 [52%]) and consolidation chemotherapy (36 [69%]),
      hyperglycaemia (28 [54%]), hypokalaemia (16 [31%]), increased aminotransferases
      (ten [19%]), hyperbilirubinaemia (nine [17%]), and haemorrhage (seven [15%]).
      Veno-occlusive disease occurred in four (8%) patients. Six (12%) patients died
      from adverse events that were deemed treatment related (five [10%] from sepsis
      and one [2%] from veno-occlusive disease). INTERPRETATION: Inotuzumab ozogamicin
      plus mini-hyper-CVD chemotherapy is a safe and active first-line therapy option
      in older patients with newly diagnosed acute lymphoblastic leukaemia and could
      represent a new therapy for this population. Randomised, phase 3 trials to
      evaluate the efficacy of this combination compared with the current standard of
      care in this setting, combination chemotherapy without inotuzumab ozogamicin, are
      warranted. FUNDING: MD Anderson Cancer Center.

PMID- 29352705
TI  - The long road towards a safe and effective treatment of chronic Chagas disease.

PMID- 29352704
TI  - Treatment of adult chronic indeterminate Chagas disease with benznidazole and
      three E1224 dosing regimens: a proof-of-concept, randomised, placebo-controlled
      trial.
AB  - BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this
      study, we investigated the safety and efficacy of three oral E1224 (a water
      soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult
      chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double
      blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with
      confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in
      Bolivia. Patients were randomised with a computer-generated randomisation list,
      which was stratified by centre and used a block size of ten. Patients were
      randomly assigned (1:1:1:1:1) to five oral treatment groups: high-dose E1224
      (duration 8 weeks, total dose 4000 mg), low-dose E1224 (8 weeks, 2000 mg), short
      dose E1224 (4 weeks + 4 weeks placebo, 2400 mg), benznidazole (60 days, 5 mg/kg
      per day), or placebo (8 weeks, E1224-matched tablets). Double-blinding was
      limited to the E1224 and placebo arms, and assessors were masked to all treatment
      allocations. The primary efficacy endpoint was parasitological response to E1224
      at the end of treatment, assessed by PCR. The secondary efficacy endpoints were
      parasitological response to benznidazole at end of treatment, assessed by PCR;
      sustainability of parasitological response until 12 months; parasite clearance
      and changes in parasite load; incidence of conversion to negative response in
      conventional and non-conventional (antigen trypomastigote chemiluminescent ELISA
      [AT CL-ELISA]) serological response; changes in levels of biomarkers; and
      complete response. The primary analysis population consisted of all randomised
      patients by their assigned treatment arms. This trial is registered with
      ClinicalTrials.gov, number NCT01489228. FINDINGS: Between July 19, 2011, and July
      26, 2012, we screened 560 participants with confirmed Chagas disease, of whom 231
      were enrolled and assigned to high-dose E1224 (n=45), low-dose E1224 (n=48),
      short-dose E1224 (n=46), benznidazole (n=45), or placebo (n=47). Parasite
      clearance was observed with E1224 during the treatment phase, but no sustained
      response was seen with low-dose and short-dose regimens, whereas 13 patients
      (29%, 95% CI 16.4-44.3) had sustained response with the high-dose regimen
      compared with four (9%, 2.4-20.4) in the placebo group (p<0.0001). Benznidazole
      had a rapid and sustained effect on parasite clearance, with 37 patients (82%,
      67.9-92.0) with sustained response at 12-month follow-up. After 1 week of
      treatment, mean quantitative PCR repeated measurements showed a significant
      reduction in parasite load in all treatment arms versus placebo. Parasite levels
      in the low-dose and short-dose E1224 groups gradually returned to placebo levels.
      Both treatments were well tolerated. Reversible, dose-dependent liver enzyme
      increases were seen with E1224 and benznidazole. 187 (81%) participants developed
      treatment-emergent adverse events and six (3%) developed treatment-emergent
      serious adverse events. Treatment-emergent adverse events were headaches, nausea,
      pruritus, peripheral neuropathy, and hypersensitivity. INTERPRETATION: E1224 is
      the first new chemical entity developed for Chagas disease in decades. E1224
      displayed a transient, suppressive effect on parasite clearance, whereas
      benznidazole showed early and sustained efficacy until 12 months of follow-up.
      Despite PCR limitations, our results support increased diagnosis and access to
      benznidazole standard regimen, and provide a development roadmap for novel
      benznidazole regimens in monotherapy and in combinations with E1224. FUNDING:
      Drugs for Neglected Diseases initiative.

PMID- 29352706
TI  - Environmental conditions in health care facilities in low- and middle-income
      countries: Coverage and inequalities.
AB  - Safe environmental conditions and the availability of standard precaution items
      are important to prevent and treat infection in health care facilities (HCFs) and
      to achieve Sustainable Development Goal (SDG) targets for health and water,
      sanitation, and hygiene. Baseline coverage estimates for HCFs have yet to be
      formed for the SDGs; and there is little evidence describing inequalities in
      coverage. To address this, we produced the first coverage estimates of
      environmental conditions and standard precaution items in HCFs in low- and middle
      income countries (LMICs); and explored factors associated with low coverage. Data
      from monitoring reports and peer-reviewed literature were systematically
      compiled; and information on conditions, service levels, and inequalities
      tabulated. We used logistic regression to identify factors associated with low
      coverage. Data for 21 indicators of environmental conditions and standard
      precaution items were compiled from 78 LMICs which were representative of 129,557
      HCFs. 50% of HCFs lack piped water, 33% lack improved sanitation, 39% lack
      handwashing soap, 39% lack adequate infectious waste disposal, 73% lack
      sterilization equipment, and 59% lack reliable energy services. Using nationally
      representative data from six countries, 2% of HCFs provide all four of water,
      sanitation, hygiene, and waste management services. Statistically significant
      inequalities in coverage exist between HCFs by: urban-rural setting, managing
      authority, facility type, and sub-national administrative unit. We identified
      important, previously undocumented inequalities and environmental health
      challenges faced by HCFs in LMICs. The information and analyses provide evidence
      for those engaged in improving HCF conditions to develop evidence-based policies
      and efficient programs, enhance service delivery systems, and make better use of
      available resources.

PMID- 29352707
TI  - Prenatal exposure to lead in France: Cord-blood levels and associated factors:
      Results from the perinatal component of the French Longitudinal Study since
      Childhood (Elfe).
AB  - BACKGROUND: As a result of the ban on lead in gasoline on 2nd January 2000, the
      French population's exposure to lead has decreased in recent years. However,
      because of the acknowledged harmful cognitive effects of lead even at low levels,
      lead exposure remains a major public health issue. In France, few biomonitoring
      data are available for exposure to lead in pregnant women and newborn. The
      purpose of the perinatal component of the French human biomonitoring (HBM)
      program was to describe levels of various biomarkers of exposure to several
      environmental pollutants, including lead, among mother-baby pairs. In this paper,
      we aimed to describe the distribution of cord blood lead levels (CBLL) in French
      mother-baby pairs, and to estimate the contribution of the main lead exposure
      risk factors to these levels. METHOD: A total of 1968 mother-baby pairs selected
      from the participants of the perinatal component of the French HBM program were
      included in the study on lead. Lead levels were analyzed in cord blood collected
      at child delivery by inductively coupled plasma-mass spectrometry (ICP-MS). The
      data collected included biological sample, socio-demographic characteristics,
      environmental and occupational exposure, and information on dietary factors.
      RESULTS: CBLL were quantified for 99.5% of the sample. The CBLL geometric mean
      was 8.30 MUg/l (95% CI [7.94-8.68]) with a 95th percentile of 24.3 MUg/l (95% CI
      [20.7-27.1]). Factors significantly associated with CBLL were tap water
      consumption, alcohol consumption, shellfish consumption, vegetable consumption,
      bread consumption, smoking, and the mother being born in countries where lead is
      often used. CONCLUSION: This study provides the first reference value for CBLL in
      a random sample of mother-baby pairs not particularly exposed to high levels of
      lead (24.3 MUg/l). A substantial decrease in CBLL over time was observed, which
      confirms the decrease of exposure to lead among the general population. CBLL
      observed in this French study were in the range of those found in recent surveys
      conducted in other countries.

PMID- 29352708
TI  - A systematic review and discussion of symptom specific cognitive behavioural
      approaches to delusions and hallucinations.
AB  - Studies on cognitive behavioural therapy for psychosis (CBTp) have developed from
      evaluating generic approaches to focusing on specific symptoms. The evidence for
      targeted studies on delusions and hallucinations was reviewed. We included
      randomized controlled trials (RCTs) examining the effect of individualized CBT
      based interventions focusing either on delusions or on hallucinations. Twelve
      suitable RCTs were identified. Four RCTs focused on delusions, of which three
      took a focused approach targeting mechanisms assumed causal to persecutory
      delusions. Eight RCTs focused on hallucinations, a common component of these
      studies being a focus on the perceived power imbalance between the voice(s) and
      the voice-hearer, to reduce distress and dysfunction. Only three RCTS were
      powered adequately; the remainder were pilot trials. All trials reported effect
      sizes against treatment-as-usual above d=0.4 on at least one primary outcome at
      post-therapy, with several effects in the large range. Effects on the primary
      outcome were maintained for five of the seven studies that had significant
      outcomes and reported a follow-up comparison, but most of the follow-up periods
      were brief. Although targeted studies are still in their infancy, the results are
      promising with a tendency towards higher effects compared to the small-to
      moderate range found for generic CBTp. In clinical practice, CBTp will need to
      continue including a range of approaches that can be adapted to patients in a
      flexible manner according to the primary goals and prevalent combination of
      symptoms. However, symptom-focused and causal-interventionist approaches are
      informative research strategies to evaluate the efficacy of separate components
      or mechanisms of generic CBTp.

PMID- 29352709
TI  - Analysis of gut microbiota diversity and auxiliary diagnosis as a biomarker in
      patients with schizophrenia: A cross-sectional study.
AB  - With the advent of sequencing technology, characterization of schizophrenia with
      underlying probing of gut microbiome can provide abundant clues for diagnosis and
      prognosis of schizophrenia. In this study, we first compared the difference of
      gut microbiota between schizophrenia patients and healthy controls by 16S rRNA
      sequencing. We further explored whether gut microbiota can be used as a biomarker
      to assist in the diagnosis of schizophrenia. We restricted inclusion criteria
      strictly to control confounding bias. Finally, we investigated differences in
      fecal microbiota between 64 schizophrenia patients and 53 healthy controls. At
      the phylum level, we found that the abundance of Proteobacteria in the
      schizophrenia patients was significantly increased. At the genus level, the
      relative abundance of Succinivibrio, Megasphaera, Collinsella, Clostridium,
      Klebsiella and Methanobrevibacter was significantly higher whereas the abundance
      of Blautia, Coprococcus, Roseburia was decreased compared to health controls. The
      receiver operating characteristic curve analysis demonstrated that 12 significant
      microbiota biomarkers were capable of being used as diagnostic factors for
      distinguishing the schizophrenia cohort from those in the control cohort (AUC =
      0.837). We performed PICRUSt analysis and found that several metabolic pathways
      differed significantly between healthy controls and schizophrenia patients,
      including vitamin B6 and fatty acid. In conclusion, there are some difference of
      gut microbiota between schizophrenia patients and healthy controls and the
      insights from this study could be used to develop microbiota-based diagnosis for
      schizophrenia.

PMID- 29352710
TI  - Changes in HepG2 spheroid behavior induced by differences in the gap distance
      between spheroids in a micropatterned culture system.
AB  - Micropatterning is a promising technique for modulating culture environments. In
      this study, we investigated the effect of spheroid separation distance on their
      properties in a micropatterned chip of HepG2 spheroids. The basic chip design
      consisted of 37 collagen spots (300 MUm in diameter) in a hexagonal arrangement
      on a glass substrate; the region without collagen-spots was modified by
      polyethylene glycol to create the non-adhesive surface. Three similar chips were
      fabricated with gap distances between collagen-spots of 500, 1000, and 1500 MUm.
      HepG2 cells adhered on the collagen spots and then formed spheroids via cell
      proliferation. Although the albumin secretion activities of HepG2 spheroids were
      almost the same in all chips, inhibition of spheroid growth and anaerobic
      metabolism were intensified when the gap distance was less than 1000 MUm.
      Additionally, such phenomena which are induced by interference effects between
      spheroids, were more pronounced at the inside region of the chip than at the
      outside region. However, the interference effect between spheroids was nearly
      avoided when the gap distance was at least 1500 MUm. Furthermore, the
      concentration of dissolved oxygen between neighboring spheroids decreased as the
      gap distance decreased, indicating that the spheroids competed for oxygen and
      became hypoxic in a way that depended on the spheroid separation distance. These
      results indicate that the spheroid separation distance is an important factor
      that can modulate the spheroid properties.

PMID- 29352711
TI  - Gold cleaning methods for preparation of cell culture surfaces for self-assembled
      monolayers of zwitterionic oligopeptides.
AB  - Self-assembled monolayers (SAMs) have been used to elucidate interactions between
      cells and material surface chemistry. Gold surfaces modified with oligopeptide
      SAMs exhibit several unique characteristics, such as cell-repulsive surfaces,
      micropatterns of cell adhesion and non-adhesion regions for control over cell
      microenvironments, and dynamic release of cells upon external stimuli under
      culture conditions. However, basic procedures for the preparation of oligopeptide
      SAMs, including appropriate cleaning methods of the gold surface before
      modification, have not been fully established. Because gold surfaces are readily
      contaminated with organic compounds in the air, cleaning methods may be critical
      for SAM formation. In this study, we examined the effects of four gold cleaning
      methods: dilute aqua regia, an ozone water, atmospheric plasma, and UV
      irradiation. Among the methods, UV irradiation most significantly improved the
      formation of oligopeptide SAMs in terms of repulsion of cells on the surfaces. We
      fabricated an apparatus with a UV light source, a rotation table, and HEPA
      filter, to treat a number of gold substrates simultaneously. Furthermore, UV
      cleaned gold substrates were capable of detaching cell sheets without serious
      cell injury. This may potentially provide a stable and robust approach to
      oligopeptide SAM-based experiments for biomedical studies.

PMID- 29352712
TI  - Evaluating new bio-hydrogen producers: Clostridium perfringens strain JJC,
      Clostridium bifermentans strain WYM and Clostridium sp. strain Ade.TY.
AB  - Three newly discovered H2 producing bacteria namely Clostridium perfringens
      strain JJC, Clostridium bifermentans strain WYM and Clostridium sp. strain Ade.TY
      originated from landfill leachate sludge have demonstrated highly efficient H2
      production. The maximum H2 production attained from these isolates are in the
      descending order of strain C. perfringens strain JJC > C. bifermentans strain WYM
      > Clostridium sp. strain Ade.TY with yield of 4.68 +/- 0.12, 3.29 +/- 0.11, and
      2.87 +/- 0.10 mol H2/mol glucose, respectively. The result has broken the
      conventional theoretical yield of 4 mol H2/mol glucose. These isolates were
      thermodynamically favourable with Gibbs free energy between -33 and -35 kJ/mol
      (under process conditions: pH 6, 37  degrees C and 5 g/L glucose). All three
      isolates favour butyrate pathway for H2 production with the ratio of acetate and
      butyrate of 0.77, 0.65 and 0.80 for strain JJC, WYM and Ade.TY, respectively.
      This study reported provides a new insight on the potential of unique bacteria in
      H2 production.

PMID- 29352713
TI  - Clinical Variables Associated With Overall Survival in Metastatic Castration
      Resistant Prostate Cancer Patients Treated With Sipuleucel-T Immunotherapy.
AB  - BACKGROUND: Sipuleucel-T is an autologous cell-based cancer immunotherapy for men
      with asymptomatic or minimally symptomatic metastatic castration-resistant
      prostate cancer (mCRPC). Its approval by the Food and Drug Administration was
      based on demonstration of an overall survival (OS) benefit in randomized placebo
      controlled phase III trials. However, treatment was associated with a prostate
      specific antigen (PSA) decline in only a small minority of patients.
      Understanding the clinical factors that are associated with OS could help guide
      treatment decisions, including patient selection and the timing of sipuleucel-T
      relative to other therapies. PATIENTS AND METHODS: We retrospectively identified
      94 mCRPC patients treated with sipuleucel-T from April 2010 to April 2016. The
      Kaplan-Meier method was used to estimate the distribution of OS. Univariate and
      multivariate Cox proportional hazard modeling was used to identify the prognostic
      factors for OS. RESULTS: With a median follow-up of 24.9 months, the median OS
      was 34.9 months. On multivariate analysis, Eastern Cooperative Oncology Group
      performance status, pretreatment PSA doubling time, and previous abiraterone
      and/or enzalutamide were significant prognostic factors for OS. CONCLUSION: A
      poorer baseline performance status, faster disease pace measured by the PSA
      doubling time, and previous novel androgen signaling inhibitor exposure could be
      important prognostic considerations for the treatment of mCRPC patients with
      sipuleucel-T. Further studies are needed to validate these findings.

PMID- 29352714
TI  - Effect of Single-agent Daily Prednisone on Outcomes and Toxicities in Metastatic
      Castration-resistant Prostate Cancer: Pooled Analysis of Prospective Studies.
AB  - The clinical effect of prednisone in metastatic castration-resistant prostate
      cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of
      randomized controlled trials that had or had not administered single-agent
      prednisone. Randomized controlled trials with a control arm that included single
      agent placebo (or no anticancer therapy) or single-agent prednisone (with or
      without placebo) were eligible for analysis. Patients receiving prednisone
      combined with other agents in the control arm were excluded. The trial
      characteristics, baseline demographic data, overall survival (OS), progression
      free survival (PFS), prostate-specific antigen (PSA) response, Response
      Evaluation Criteria In Solid Tumors response, and toxicities were recorded. The
      effect of prednisone was investigated for significance in bivariate models,
      adjusting for age, pre- and post-docetaxel status, Eastern Cooperative Oncology
      Group performance status, and trial publication year. Eighteen trials were
      included; 9 had control arms that contained prednisone (n = 2831) and 9 did not
      (n = 2784). No significant differences were identified for OS or toxicities of
      any grade. A significantly greater PSA response rate (18.8% vs. 2.5%; P = .023)
      and a trend toward more frequent grade >= 3 fluid retention (1.0% vs. 0.4%; P =
      .097) was seen in the prednisone group. Prednisone was also significantly
      associated with PFS after adjusting for docetaxel status. Single-agent prednisone
      for mCRPC did not improve OS but was associated with a greater PSA response rate
      and PFS. Overall and grade >= 3 toxicities were not significantly different with
      prednisone. With the exception of concurrent use with abiraterone or for
      palliative purposes, the routine use of prednisone for mCRPC appears unnecessary.

PMID- 29352715
TI  - Patient-Friendly Summary of the ACR Appropriateness Criteria Headache.

PMID- 29352717
TI  - Should We Use Cell of Origin and Dual-protein Expression in Treating DLBCL?
AB  - Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R
      CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
      therapy is highly variable and dependent on a number of clinical, biologic, and
      genetic features. The identification of molecular heterogeneity via gene
      expression profiling dichotomizes patients based on the cell of origin (COO)
      model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC)
      subsets, with ABC-DLBCL having a worse outcome. Along with the COO
      classification, other molecular phenotypes have also been identified, further
      highlighting the clinical and biologic complexity of this disease. Double-hit
      lymphomas, with concurrent chromosomal translocations of the MYC and BLC2 genes,
      or less commonly MYC and BCL6 genes, are associated with an aggressive clinical
      course and adverse outcomes when treated with R-CHOP. Furthermore, dual
      overexpression of MYC and BCL2 proteins has emerged as an important adverse
      prognostic factor, can be present through different mechanisms in both GCB and
      ABC subsets, and further complicates treatment considerations. Studies
      investigating the biologic underpinnings of these diverse subtypes have revealed
      a number of novel targets, which may provide therapeutic benefit. Moving forward,
      clinical trials focusing on molecular subsets of DLBCL, and incorporating
      rational targeted agents, will ideally lead to improved outcomes and allow a more
      personalized treatment approach. This review will focus on emerging data
      regarding DLBCL management based on either COO or dual overexpression of MYC/BCL2
      proteins.

PMID- 29352716
TI  - [Echographic diagnosis of missed early miscarriage: Assessment of image quality].
AB  - OBJECTIVE: Ultrasound examination plays a central role in case of suspected non
      viable pregnancy. A wrong diagnosis might have major consequence in terms of
      inadequate care, especially in cases of false positive non-viable pregnancy
      diagnosis. Ultrasound criterions are today well defined. Our objective was to
      evaluate the feasibility and reproducibility of a novel image-quoting method of
      first-trimester non-viable pregnancy. METHODS: Thirty images of non-viable
      pregnancy were twice evaluated with blinded proofreading. Two quotations were
      evaluated: the first for the images of gestational sacs without embryo
      (gestational sac score), the second for the images with embryo (embryo score).
      RESULTS: The ICC (interclass correlation coefficient) was>0.75 for inter- and
      intra-observer reproducibility both for the quotations of the gestational sac and
      for the embryo with a low variability. Reproducibility of quoting crown rump
      length measurements <5mm was low at first proofreading but after adjustment of
      the quoting modalities, ICC was also>0.75. CONCLUSION: The inter- and intra
      observer reproducibility of our quoting methods is high with a low variability.
      They might be a useful tool in current practice in the future.

PMID- 29352718
TI  - Consolidative Radiotherapy to Residual Masses After Chemotherapy Is Associated
      With Improved Outcome in Diffuse Large B-Cell Lymphoma. A Retrospective,
      Population-Based Study.
AB  - BACKGROUND: The role of consolidative radiotherapy (RT) in advanced diffuse large
      B-cell lymphoma (DLBCL) is not established. PATIENTS AND METHODS: In a population
      based retrospective analysis of patients with DLBCL in Western Norway during 2003
      to 2008, 170 consecutive patients admitted to Haukeland University Hospital (HUS)
      and 94 to Stavanger University Hospital (SUS) were included. The mean age was 64
      years (range, 17-95 years), 147 patients (56%) were male, 80 patients (30%) had
      stage I/II, 126 patients (48%) stage III/IV, and 57 patients (22%) had primary
      extranodal disease. RESULTS: There were no differences between hospitals in
      patient characteristics, use of rituximab, number of chemotherapy courses or
      cumulative doses, or in distribution of response categories after chemotherapy.
      The use of RT was significantly different: 17 patients (23%) received RT at SUS
      and 92 patients (65%) at HUS (P < .001). For 219 patients with International
      Prognostic Index (IPI) score of 0 to 3, 5-year cancer-specific survival (CSS) was
      67% at SUS and 81% at HUS (P = .012). For 73 patients with complete response
      after chemotherapy there were no differences in survival between patients with
      and without RT. For 138 patients with any residual mass after chemotherapy, there
      were highly significant differences in favor of receiving RT (n = 81) versus no
      RT (n = 57): 5-year CSS 89% versus 69% (P < .001), and 5-year overall survival
      82% versus 59% (P = .005). The effect of RT on residual mass was evident in most
      subgroups, mainly in low to intermediate risk, but not in high-risk (IPI 4-5)
      patients. CONCLUSION: With the limitations of a retrospective study, these data
      suggest that consolidative RT might improve survival in DLBCL patients with a
      residual mass after chemotherapy, also in advanced disease.

PMID- 29352719
TI  - Prognostic Testing Patterns and Outcomes of Chronic Lymphocytic Leukemia Patients
      Stratified by Fluorescence In Situ Hybridization/Cytogenetics: A Real-world
      Clinical Experience in the Connect CLL Registry.
AB  - INTRODUCTION: Prognostic genetic testing is recommended for patients with chronic
      lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities,
      such as del(17p), del(11q), and unmutated IgHV, can predict the depth and
      durability of the response to CLL therapy. PATIENTS AND METHODS: In the present
      analysis of the Connect CLL Registry (ClinicalTrials.gov identifier,
      NCT01081015), a prospective observational cohort study of patients treated across
      199 centers, the patterns of prognostic testing and outcomes of patients with
      unfavorable-risk genetics were analyzed. From 2010 to 2014, 1494 treated patients
      were enrolled in the registry by line of therapy (LOT), and stratified by the
      results of cytogenetic/fluorescence in situ hybridization (FISH) testing into 3
      risk levels: unfavorable (presence of del[17p] or del[11q]), favorable (absence
      of del[17p] and del[11q]), and unknown. RESULTS: Cytogenetic/FISH testing was
      performed in 861 patients (58%) at enrollment; only 40% of these patients were
      retested before starting a subsequent LOT. Of those enrolled at the first LOT,
      unfavorable-risk patients had inferior event-free survival compared with
      favorable-risk patients (hazard ratio, 1.60; P = .001). Event-free survival was
      inferior with bendamustine-containing regimens (P < .0001). Event-free survival
      did not differ significantly between risk groups for patients treated with
      ibrutinib or idelalisib in the relapse/refractory setting. The predictors of
      reduced event-free survival included unfavorable-risk genetics, age >= 75 years,
      race, and treatment choice at enrollment. CONCLUSION: The present study has shown
      that prognostic cytogenetic/FISH testing is infrequently performed and that
      patients with unfavorable-risk genetics treated with immunochemotherapy
      combinations have worse outcomes. This underscores the importance of performing
      prognostic genetic testing for all CLL patients to guide treatment.

PMID- 29352720
TI  - Selection of the Best of 2017 in Left Atrial Appendage Occlusion: Filling the Gap
      in Knowledge.

PMID- 29352721
TI  - Hyperconnective and hypoconnective cortical and subcortical functional networks
      in multiple system atrophy.
AB  - INTRODUCTION: In multiple system atrophy (MSA), the organization of the
      functional brain connectivity within cortical and subcortical networks and its
      clinical correlates remains to be investigated. METHODS: Whole-brain based
      'resting-state' fMRI data were obtained from 22 MSA patients (11 MSA-C, 11 MSA-P)
      and 22 matched healthy controls, together with standardized clinical assessment
      and video-oculographic recordings (EyeLink(r)). RESULTS: MSA patients vs.
      controls showed significantly higher ponto-cerebellar functional connectivity and
      lower default mode network connectivity (p < .05, corrected). No differences were
      observed in the motor network and in the control network. The higher the ponto
      cerebellar network functional connectivity was, the more pronounced was smooth
      pursuit impairment. CONCLUSION: This functional connectivity analysis supports a
      network-dependent combination of hyper- and hypoconnectivity states in MSA, in
      agreement with adaptive compensatory responses (hyperconnectivity) and a function
      disconnection syndrome (hypoconnectivity) that may occur in a consecutive
      sequence.

PMID- 29352722
TI  - Daily intake of Mucuna pruriens in advanced Parkinson's disease: A 16-week,
      noninferiority, randomized, crossover, pilot study.
AB  - BACKGROUND: Thousands of individuals with Parkinson's disease (PD) in low-income
      countries have limited access to marketed levodopa preparations. Mucuna pruriens
      (MP), a levodopa-containing leguminous plant growing in tropical areas, may be a
      sustainable alternative therapy for indigent patients. Single-dose intake of MP
      proved noninferior to marketed levodopa preparations. METHODS: Fourteen PD
      patients with motor fluctuations and dyskinesias received MP powder (obtained
      from roasted seeds) and marketed levodopa/carbidopa (LD/CD) in a randomized order
      and crossover design over a 16-week period. Efficacy measures were changes in
      quality of life, motor and non-motor symptoms, and time with good mobility
      without troublesome dyskinesias. Safety measures included tolerability, frequency
      of adverse events, changes in laboratory indices and electrocardiogram. RESULTS:
      Daily intake of MP was associated with a variable clinical response, especially
      in terms of tolerability. Seven patients (50%) discontinued MP prematurely due to
      either gastrointestinal side-effects (n = 4) or progressive worsening of motor
      performance (n = 3), while nobody discontinued during the LD/CD phase. In those
      who tolerated MP, clinical response to MP was similar to LD/CD on all efficacy
      outcome measures. Patients who dropped out entered a study extension using MP
      supernatant water (median[IQR], 16 [7-20] weeks), which was well tolerated.
      CONCLUSIONS: The overall benefit provided by MP on the clinical outcome was
      limited by tolerability issues, as one could expect by the relatively rapid
      switch from LD/CD to levodopa alone in advanced PD. Larger parallel-group studies
      are needed to identify appropriate MP formulation (e.g. supernatant water),
      titration scheme and maintenance dose to minimize side-effects in the long-term.
      CLINICAL TRIALS. GOV IDENTIFIER: NCT02680977.

PMID- 29352724
TI  - Indications for starting ART.

PMID- 29352723
TI  - Which HIV-infected adults with high CD4 T-cell counts benefit most from immediate
      initiation of antiretroviral therapy? A post-hoc subgroup analysis of the START
      trial.
AB  - BACKGROUND: Immediate initiation of antiretroviral therapy (ART) in asymptomatic
      adults with CD4 counts higher than 500 cells per MUL, as recommended, might not
      always be possible in resource-limited settings. We aimed to identify subgroups
      of individuals who would benefit most from immediate treatment. METHODS: The
      START trial was a randomised controlled trial in asymptomatic, HIV-positive
      adults previously untreated with ART. Participants with CD4 counts higher than
      500 cells per MUL were randomly assigned to receive immediate ART or to defer ART
      until CD4 counts were lower than 350 cells per MUL. The primary endpoint of the
      study was serious AIDS-defining illnesses or death from AIDS and serious non-AIDS
      illnesses or non-AIDS-related death. In this post-hoc analysis, we estimated
      event rates and absolute risk reduction with immediate versus deferred ART,
      overall and by subgroup. Subgroups were prespecified in the study protocol or
      formed post hoc on the basis of baseline characteristics associated with
      morbidity and mortality in people with HIV. For continuous characteristics,
      approximate terciles were chosen as subgroup cutoff points, unless different
      cutoffs were clinically meaningful (eg, age >=50 years). We estimated the number
      needed to treat immediately with ART for 1 year to prevent one primary event.
      Heterogeneity in the absolute risk reduction between subgroups was assessed with
      bootstrap tests. The START trial is registered with ClinicalTrials.gov, number
      NCT00867048. FINDINGS: Between April 15, 2009, and Dec 23, 2013, we enrolled 4684
      participants from 35 countries across five continents, of whom 2325 were assigned
      to immediate ART and 2359 were assigned to deferred ART. The primary endpoint
      occurred in 42 participants in the immediate ART group (0.58 events per 100
      person-years) and 100 participants in the deferred ART group (1.37 events per 100
      person-years). The absolute risk reduction was 0.80 (95% CI 0.48-1.13) per 100
      person-years with immediate treatment, and the number needed to treat immediately
      to prevent one event was 126 (95% CI 89-208). Significant heterogeneity in
      absolute risk reduction with immediate ART was found across subgroups according
      to age (p=0.0022), CD4 to CD8 ratio (p=0.0007), and plasma HIV RNA viral load
      (p=0.033) at baseline. The highest absolute risk reductions and the lowest
      numbers needed to treat were found in participants aged 50 years or older, those
      with CD4 to CD8 ratios of less than 0.5, and those with plasma HIV RNA viral
      loads of 50 000 copies per mL or higher. INTERPRETATION: Asymptomatic, ART-naive
      adults with CD4 counts higher than 500 cells per MUL who are older, have a low
      CD4 to CD8 ratio, or a high plasma HIV RNA viral load benefit most from immediate
      initiation of ART and should be prioritised for treatment. FUNDING: US National
      Institute of Allergy and Infectious Diseases.

PMID- 29352725
TI  - Longitudinal evaluation of a training program to promote routine antenatal
      enquiry for domestic violence by midwives.
AB  - BACKGROUND: Routine enquiry about domestic violence during pregnancy is accepted
      best practice. Training is essential to improve knowledge and practice. Few
      studies have undertaken a comprehensive evaluation of training impact over time.
      AIM: To evaluate the longitudinal impact of a domestic violence training and
      support program to promote midwives' routine antenatal enquiry for domestic
      violence using a mixed methods design. METHOD: Data sources included (1) surveys
      of midwives at 6 months post-training, (2) interviews with key stakeholders at 12
      months, (3) chart audit data of screening, risk, and disclosure rates (for 16
      months). Measures included midwives' knowledge, preparation for routine enquiry,
      knowledge of domestic violence and perceptions of impact of the training and
      support for practice change. FINDINGS: Forty (out of 83) participant surveys
      could be matched and responses compared to baseline and post-training scores.
      Wilcoxon signed-rank test identified that all 6-month follow-up scores were
      significantly higher than those at baseline. Level of preparedness increased from
      42.3 to 51.05 (Z=4.88, p<.001); and knowledge scores increased from a mean of
      21.15 to 24.65 (Z=4.9, p<.001). Most participants (>90%) reported improved
      confidence to undertake routine inquiry. A chart audit of screening rates
      revealed that of the 6671 women presenting for antenatal care, nearly 90% were
      screened. Disclosure of domestic violence was low (<2%) with most women at risk
      or experiencing violence declining referral. CONCLUSIONS: Training, support
      processes, and referral pathways, contributed to midwives' sustained preparedness
      and knowledge to conduct routine enquiry and support women disclosing domestic
      violence.

PMID- 29352726
TI  - Corrigendum to "Bombesin-like receptor 3 (Brs3) expression in glutamatergic, but
      not GABAergic, neurons is required for regulation of energy metabolism" [Mol
      Metabol 6 (2017) 1540-1550].

PMID- 29352727
TI  - Re-evaluation of target lipid model-derived HC5 predictions for hydrocarbons.
AB  - The target lipid model (TLM) has been previously applied to predict the aquatic
      toxicity of hydrocarbons and other nonionic organic chemicals and for deriving
      the concentrations above which 95% of species should be protected (HC5 values).
      Several concerns have been identified with the TLM-derived HC5 when it is applied
      in a substance risk assessment context. These shortcomings were addressed by
      expanding the acute and chronic toxicity databases to include more diverse
      taxonomic groups and increase the number of species. The TLM was recalibrated
      with these expanded databases, resulting in critical target lipid body burdens
      and acute-to-chronic ratios that met the required guidelines for using species
      sensitivity distributions in substance risk assessment. The HC5 equation was
      further revised to consider covarying model parameters. The calculated HC5 values
      derived from the revised TLM framework were validated using an independent data
      set for hydrocarbons comprising 106 chronic values across plants, invertebrates,
      and fish. Assuming a sum binomial distribution, the 95% confidence limit for a 5%
      failure is between 0.8 and 9.2%. Eight chronic values fell below the HC5,
      corresponding to an excursion of 7.5%, which falls within the expected
      uncertainty bounds. Thus, calculated HC5s derived from the revised TLM framework
      were found to be consistent with the intended protection goals. Environ Toxicol
      Chem 2018;37:1579-1593. (c) 2018 SETAC.

PMID- 29352728
TI  - Differential proteomic analysis of synovial fluid from hip arthroplasty patients
      with a pseudotumor vs. Periprosthetic osteolysis .
AB  - Adverse tissue reactions to metal implants, including pseudotumors, can
      compromise implant functionality and survivorship. The identification of specific
      proteins in the synovial fluid (SF) of hip arthroplasty patients with a
      pseudotumor may lead to a better understanding of the underlying pathomechanisms.
      The objective of the present study was to compare the protein content of SF from
      patients with a short-term metal-on-metal hip implant associated with a
      pseudotumor and patients with a long-term metal-on-polyethylene hip implant
      associated with periprosthetic osteolysis. Discovery proteomics was used to
      identify differentially abundant proteins in albumin-depleted SF. In toto, 452
      distinct proteins (present in at least half of the patients in one or both
      groups) were identified. Thirty of these 452 proteins were differentially
      abundant between the two groups, including two potential biomarkers: 6
      phosphogluconate dehydrogenase (which plays a major protective role against
      oxidative stress) for the pseudotumor group, and scavenger receptor cysteine-rich
      type 1 protein M130 (which is involved in low-grade inflammation) for the
      periprosthetic osteolysis group. Other differentially abundant proteins
      identified suggest the presence of an adaptive immune response (particularly a
      type-IV hypersensitivity reaction), necrosis, and greater oxidative stress in
      patients with a pseudotumor. They also suggest the presence of an innate immune
      response, oxidative stress, tissue remodeling, and apoptosis in both patient
      groups, although differences in the specific proteins identified in each group
      point to differences in the pathomechanisms. Overall, results provide insights
      into the molecular mechanisms underlying metal-related pseudotumors and
      periprosthetic osteolysis, and may ultimately help elucidate pseudotumor etiology
      and assess the risk that asymptomatic pseudotumors will develop into an
      aggressive lesion. (c) 2018 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 36:1849-1859, 2018.

PMID- 29352729
TI  - Voxelotor (GBT440), a first-in-class hemoglobin oxygen-affinity modulator, has
      promising and reassuring preclinical and clinical data.

PMID- 29352730
TI  - Teaching of anatomical sciences: A blended learning approach.
AB  - Blended learning is the integration of different learning approaches, new
      technologies, and activities that combine traditional face-to-face teaching
      methods with authentic online methodologies. Although advances in educational
      technology have helped to expand the selection of different pedagogies, the
      teaching of anatomical sciences has been challenged by implementation
      difficulties and other limitations. These challenges are reported to include lack
      of time, costs, and lack of qualified teachers. Easy access to online information
      and advances in technology make it possible to resolve these limitations by
      adopting blended learning approaches. Blended learning strategies have been shown
      to improve students' academic performance, motivation, attitude, and
      satisfaction, and to provide convenient and flexible learning. Implementation of
      blended learning strategies has also proved cost effective. This article provides
      a theoretical foundation for blended learning and proposes a validated framework
      for the design of blended learning activities in the teaching and learning of
      anatomical sciences. Clin. Anat. 31:323-329, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29352731
TI  - Induced cumulus expansion of poor quality buffalo cumulus oocyte complexes by
      Interleukin-1beta improves their developmental ability.
AB  - The present study was conceived with the aim of modulating the cumulus expansion
      characteristics of poor quality (BCB-) buffalo oocyte complexes (COCs) in order
      to improve their fertilization outcomes. BCB- COCs were subjected to in vitro
      maturation (IVM) in presence of Interleukin-1 beta (IL-1beta) along with BCB-
      (control) and good quality (BCB+) COCs. Results were assessed morphologically, by
      scanning electron microscopy (SEM) and by expression analysis of cumulus
      expansion related genes. Also, numbers of zona pellucida bound spermatozoa were
      counted and development rates of oocytes were monitored under different groups.
      Expression of versican isoforms and ADAMTS-1 was observed to be significantly
      different between cumulus cells of BCB+ and BCB- COCs. Upon IL-1beta
      supplementation, ADAMTS-1 expression increased in BCB- COCs along with
      corresponding cumulus expansion rates. SEM analysis also revealed improved
      cumulus expansion in IL-1beta supplemented BCB- COCs. HAS2 and TNFAIP-6 were
      significantly up-regulated after IL-1beta supplementation while PTGS2 expression
      remained unaffected. Significantly more numbers of sperms crossed the cumulus
      barrier, especially in 100 ng/mL IL-1beta supplemented COCs. Besides, cleavage
      and blastocyst development rates were also improved upon IL-1beta addition. We
      concluded that IL-1beta supplementation in IVM medium can improve cumulus
      expansion and development ability of poor quality buffalo oocytes.

PMID- 29352733
TI  - Localization of palmitoylated and activated G protein alpha-subunit in
      Dictyostelium discoideum.
AB  - Guanine nucleotide-binding proteins (G proteins) act as molecular switches to
      regulate many fundamental cellular processes. The lipid modification,
      palmitoylation, can be considered as a key factor for proper G protein function
      and plasma membrane localization. In Dictyostelium discoidum, Galpha2 is
      essential for the chemotactic response to cAMP in their developmental life cycle.
      However, the regulation of Galpha2 with respect to palmitoylation, activation and
      Gbetagamma association is less clear. In this study, Galpha2 is shown to be
      palmitoylated on Cys-4 by [3 H]palmitate labeling. Loss of this palmitoylation
      site results in redistribution of Galpha2 within the cell and poor D. discoideum
      development. Cellular re-localization is also observed for activated Galpha2. In
      the membrane fraction, Galpha2-wt (YFP) is highly enriched in a low-density
      membrane fraction, which is palmitoylation-dependent. Activated Galpha2 monomer
      and heterotrimer are shifted to two different higher-density fractions. These
      results broaden our understanding of how G protein localization and function are
      regulated inside the cells.

PMID- 29352732
TI  - Long-term effects of crizotinib in ALK-positive tumors (excluding NSCLC): A phase
      1b open-label study.
AB  - Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is
      approved for treatment of patients with ALK-positive or ROS1-positive advanced
      non-small-cell lung cancer (NSCLC). However, ALK rearrangements are also
      implicated in other malignancies, including anaplastic large-cell lymphoma and
      inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single
      arm, open-label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK
      positive advanced malignancies other than NSCLC were to receive a starting dose
      of crizotinib 250 mg twice daily. Primary endpoints were safety and objective
      responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or
      National Cancer Institute International Response Criteria. Forty-four patients
      were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective
      response rate was 53% (95% confidence interval [CI], 28-77) for lymphoma, with 8
      complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30-93) for
      IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2-36) for other tumors, with 2 PRs in
      patients affected by colon carcinoma and medullary thyroid cancer, respectively.
      The median duration of treatment was almost 3 years for patients with lymphoma
      and IMTs, with 2-year progression-free survival of 63% and 67%, respectively. The
      most common treatment-related adverse events were diarrhea (45.5%) and vision
      disorders (45.5%), mostly grade 1. These findings indicate strong and durable
      activity of crizotinib in ALK-positive lymphomas and IMTs. The safety profile was
      consistent with the known safety profile of crizotinib even with long-term
      treatment.

PMID- 29352734
TI  - Concise Review: Resistance to Tyrosine Kinase Inhibitors in Non-Small Cell Lung
      Cancer: The Role of Cancer Stem Cells.
AB  - Among the potential mechanisms involved in resistance to tyrosine kinase
      inhibitors (TKIs) in non-small cell lung cancer, the manifestation of stem-like
      properties in cancer cells seems to have a crucial role. Alterations involved in
      the development of TKI resistance may be acquired in a very early phase of
      tumorigenesis, supporting the hypothesis that these aberrations may be present in
      cancer stem cells (CSCs). In this regard, the characterization of tumor subclones
      in the initial phase and the identification of the CSCs may be helpful in
      planning a specific treatment to target selected biomarkers, suppress tumor
      growth, and prevent drug resistance. The aim of this review is to elucidate the
      role of CSCs in the development of resistance to TKIs and its implication for the
      management of patients. Stem Cells 2018;36:633-640.

PMID- 29352736
TI  - Safety of anticoagulation in patients with atrial fibrillation and MDS/AML
      complicated by thrombocytopenia: An unresolved challenge: Can they be managed? A
      report of three cases and literature review.

PMID- 29352737
TI  - Bronchiolitis obliterans syndrome is associated with increased p-glycoprotein
      expression and loss of glucocorticoid receptor from steroid-resistant
      proinflammatory CD8+ T cells.
AB  - Immunosuppressive therapy fails to suppress the production of proinflammatory
      cytokines, particularly by CD8+ T cells, in stable lung transplant recipients and
      those undergoing chronic rejection, suggesting that some patients may become
      relatively resistant to immunosuppressants such as glucocorticoids (GC). We have
      shown loss of GC receptor (GCR) from the CD8+ cells, and we hypothesized that the
      drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved in
      lymphocyte steroid resistance following lung transplant. Pgp/GCR expression and
      interferon (IFN)-gamma/tumour necrosis factor (TNF)-alpha proinflammatory
      cytokine production was measured in blood lymphocytes from 15 stable lung
      transplant patients, 10 patients with bronchiolitis obliterans syndrome (BOS) and
      10 healthy aged-matched controls (+/- prednisolone +/- Pgp inhibitor, cyclosporin
      A +/- GCR activator, Compound A) using flow cytometry. Both Pgp+ and Pgp-
      lymphocyte subsets from all subjects produced IFN-gamma/TNF-alpha proinflammatory
      cytokines. Pgp expression was increased in CD8+ Pgp+ T cells and correlated with
      IFN-gamma/TNF-alpha expression and BOS grade. Reduced GCR was observed in CD8+
      Pgp- T, natural killer (NK) T-like and NK cells from stable patients compared
      with controls, and reduced further in CD8+ Pgp- T cells in BOS. The addition of
      2.5 ng/ml cyclosporin A and 1 uM prednisolone inhibit IFN-gamma/TNF-alpha
      production significantly by CD8+ Pgp+ T cells from BOS patients. The addition of
      10 uM Compound A and 1 uM prednisolone inhibit IFN-gamma/TNF-alpha production
      significantly by CD8+ Pgp- T cells from BOS patients. BOS is associated with
      increased Pgp expression and loss of GCR from steroid-resistant proinflammatory
      CD8+ T cells. Treatments that inhibit Pgp and up-regulate GCR in CD8+ T cells may
      improve graft survival.

PMID- 29352735
TI  - Winner of the society for biomaterials young investigator award for the annual
      meeting of the society for biomaterials, April 11-14, 2018, Atlanta, GA: S
      nitrosated poly(propylene sulfide) nanoparticles for enhanced nitric oxide
      delivery to lymphatic tissues.
AB  - Nitric oxide (NO) is a therapeutic implicated for the treatment of diseases
      afflicting lymphatic tissues, which range from infectious and cardiovascular
      diseases to cancer. Existing technologies available for NO therapy, however,
      provide poor bioactivity within lymphatic tissues. In this work, we address this
      technology gap with a NO encapsulation and delivery strategy leveraging the
      formation of S-nitrosothiols on lymphatic-targeting pluronic-stabilized,
      poly(propylene sulfide)-core nanoparticles (SNO-NP). We evaluated in vivo the
      lymphatic versus systemic delivery of NO resulting from intradermal
      administration of SNO-NP benchmarked against a commonly used, commercially
      available small molecule S-nitrosothiol NO donor, examined signs of toxicity
      systemically as well as localized to the site of injection, and investigated SNO
      effects on lymphatic transport and NP uptake by lymph node (LN)-resident cells.
      Donation of NO from SNO-NP, which scaled in proportion to the total administered
      dose, enhanced LN accumulation by two orders of magnitude without substantially
      reducing lymphatic transport of NP or the viability and extent of NP uptake by LN
      resident cells. Additionally, NO delivery by SNO-NP was accompanied by low-to
      negligible NO accumulation in systemic tissues with no apparent inflammation.
      These results suggest the utility and selectivity of SNO-NP for the targeted
      treatment of NO-regulated diseases that afflict lymphatic tissues. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1463-1475, 2018.

PMID- 29352738
TI  - Persistent pain following common outpatient surgeries in children: A multicenter
      study in Italy.
AB  - INTRODUCTION: The prevalence of persistent postsurgical pain in children is over
      20% after major surgeries; however, data are scarce on the prevalence, character,
      and risk factors among children undergoing common ambulatory surgeries. The
      primary aim of this study was to evaluate the prevalence of persistent pain
      following pediatric ambulatory surgery at 1, 3, and 6 months. Secondary aims were
      to identify risk factors and characterize the pain and consequences of persistent
      postsurgical pain. METHODS: ASA I-II, ages 1 month to 16 years old, undergoing
      elective hypospadias repair, herniorraphy, orchiopexy, and orthopedic surgery
      were enrolled in a prospective, longitudinal, observational study at 3 pediatric
      centers in Italy. All patients received general plus regional anesthesia.
      Postoperative pain was evaluated using age appropriate pain scales at 1 and 3
      hours. At 1, 3, and 6 months, pain scores were obtained and Parent's
      Postoperative Pain Measures (<8 yo) and Child Activity Limitations Interview (>8
      yo) surveys were administered. RESULTS: About 350 patients completed the study.
      The prevalence of pain at 1, 3, and 6 months was 24% (84/350), 6.0% (21/350), and
      4.0% (14/350), respectively. Inguinal herniorraphy patients experienced
      significantly higher pain at all 3-time points; 35.6%, 14.9%, and 9.2%. There was
      no significant association between mean pain scores >4 in PACU and persistent
      pain. Pain persisting at 6 months had neuropathic characteristics and frequently
      interfered with daily activities and sleep. CONCLUSION: Our data support the
      presence of persistent pain in pediatric patients after common surgeries. Most
      patients who developed persistent pain at 6 months had pain at 1 month. We
      recommend questioning at follow-up visit about persistent pain and functional
      impairment with follow-up until resolution.

PMID- 29352740
TI  - Coordinates for the somatosensory homunculus.

PMID- 29352739
TI  - Determination of protein oligomeric structure from small-angle X-ray scattering.
AB  - Small-angle X-ray scattering (SAXS) is useful for determining the oligomeric
      states and quaternary structures of proteins in solution. The average molecular
      mass in solution can be calculated directly from a single SAXS curve collected on
      an arbitrary scale from a sample of unknown protein concentration without the
      need for beamline calibration or protein standards. The quaternary structure in
      solution can be deduced by comparing the experimental SAXS curve to theoretical
      curves calculated from proposed models of the oligomer. This approach is
      especially robust when the crystal structure of the target protein is known, and
      the candidate oligomer models are derived from the crystal lattice. When SAXS
      data are obtained at multiple protein concentrations, this analysis can provide
      insight into dynamic self-association equilibria. Herein, we summarize the
      computational methods that are used to determine protein molecular mass and
      quaternary structure from SAXS data. These methods are organized into a workflow
      and demonstrated with four case studies using experimental SAXS data from the
      published literature.

PMID- 29352741
TI  - Band 3 phosphorylation induces irreversible alterations of stored red blood
      cells.

PMID- 29352742
TI  - Cambogin suppresses dextran sulphate sodium-induced colitis by enhancing Treg
      cell stability and function.
AB  - BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is a chronic and
      relapsing inflammatory disorder of the gastrointestinal tract, and an impaired
      immune response plays a critical role in IBD. The current drugs and therapies for
      IBD treatment are of limited use, therefore, there is a need to find novel drugs
      or therapies for this disease. We investigated the effect of cambogin in a mouse
      model of dextran sulphate sodium (DSS)-induced colitis and whether cambogin
      attenuates inflammation via a Treg-cell-mediated effect on the immune response.
      EXPERIMENTAL APPROACH: Chronic colitis was established in mice using 2% DSS, and
      cambogin (10 mg.kg-1 , p.o.) was administered for 10 days. Body weight, colon
      length and colon histology were assessed. Cytokine production was measured using
      elisa and quantitative real-time PCR. To evaluate the mechanism of cambogin,
      human CD4+ CD25hi CD127lo Treg cells were isolated from peripheral blood
      mononuclear cells. Major signalling profiles involved in Treg cell stability were
      measured. KEY RESULTS: Cambogin attenuated diarrhoea, colon shortening and colon
      histological injury and IL-6, IFN-gamma and TNF-alpha production in DSS-treated
      mice. Cambogin also up-regulated Treg cell numbers in both the spleen and
      mesenteric lymph nodes. Furthermore, cambogin (10 MUM) prevented Foxp3 loss in
      human primary Treg cells in vitro, and promoted USP7-mediated Foxp3
      deubiquitination and increased Foxp3 protein expression in LPS-treated cells.
      CONCLUSIONS AND IMPLICATIONS: The effect of cambogin on DSS-induced colitis is
      expedited by a Treg-cell-mediated modification of the immune response, suggesting
      that cambogin could be applied as a novel agent for treating colitis and other
      Treg cell-related diseases.

PMID- 29352743
TI  - Co-Transplantation of Adipose Tissue-Derived Stromal Cells and Olfactory
      Ensheathing Cells for Spinal Cord Injury Repair.
AB  - Patients suffering from spinal cord injury (SCI) still have a dismal prognosis.
      Despite all the efforts developed in this area, currently there are no effective
      treatments. Therefore, cell therapies have been proposed as a viable alternative
      to the current treatments used. Adipose tissue-derived stromal cells (ASCs) and
      olfactory ensheathing cells (OECs) have been used with promising results in
      different models of SCI, namely due to the regenerative properties of the
      secretome of the first, and the guidance capability of the second. Using an in
      vitro model of axonal growth, the dorsal root ganglia explants, we demonstrated
      that OECs induce neurite outgrowth mainly through cell-cell interactions, while
      ASCs' effects are strongly mediated by the release of paracrine factors. A
      proteomic analysis of ASCs' secretome revealed the presence of proteins involved
      in VEGF, PI3K, and Cadherin signaling pathways, which may be responsible for the
      effects observed. Then, the cotransplantation of ASCs and OECs showed to improve
      motor deficits of SCI-rats. Particular parameters of movement such as stepping,
      coordination, and toe clearance were improved in rats that received the
      transplant of cells, in comparison to nontreated rats. A histological analysis of
      the spinal cord tissues revealed that transplantation of ASCs and OECs had a
      major effect on the reduction of inflammatory cells close the lesion site. A
      slight reduction of astrogliosis was also evident. Overall, the results obtained
      with the present work indicate that the cotransplantation of ASCs and OECs brings
      important functional benefits to the injured spinal cord. Stem Cells 2018;36:696
      708.

PMID- 29352744
TI  - Crystal structure of ADP-dependent glucokinase from Methanocaldococcus jannaschii
      in complex with 5-iodotubercidin reveals phosphoryl transfer mechanism.
AB  - ADP-dependent glucokinase (ADPGK) is an alternative novel glucose phosphorylating
      enzyme in a modified glycolysis pathway of hyperthermophilic Archaea. In contrast
      to classical ATP-dependent hexokinases, ADPGK utilizes ADP as a phosphoryl group
      donor. Here, we present a crystal structure of archaeal ADPGK from
      Methanocaldococcus jannaschii in complex with an inhibitor, 5-iodotubercidin, d
      glucose, inorganic phosphate, and a magnesium ion. Detailed analysis of the
      architecture of the active site allowed for confirmation of the previously
      proposed phosphorylation mechanism and the crucial role of the invariant arginine
      residue (Arg197). The crystal structure shows how the phosphate ion, while
      mimicking a beta-phosphate group, is positioned in the proximity of the glucose
      moiety by arginine and the magnesium ion, thus providing novel insights into the
      mechanism of catalysis. In addition, we demonstrate that 5-iodotubercidin
      inhibits human ADPGK-dependent T cell activation-induced reactive oxygen species
      (ROS) release and downstream gene expression, and as such it may serve as a model
      compound for further screening for hADPGK-specific inhibitors.

PMID- 29352745
TI  - Negative supercoiling of DNA by gyrase is inhibited in Salmonella enterica
      serovar Typhimurium during adaptation to acid stress.
AB  - DNA in intracellular Salmonella enterica serovar Typhimurium relaxes during
      growth in the acidified (pH 4-5) macrophage vacuole and DNA relaxation correlates
      with the upregulation of Salmonella genes involved in adaptation to the
      macrophage environment. Bacterial ATP levels did not increase during adaptation
      to acid pH unless the bacterium was deficient in MgtC, a cytoplasmic-membrane
      located inhibitor of proton-driven F1 F0 ATP synthase activity. Inhibiting ATP
      binding by DNA gyrase and topo IV with novobiocin enhanced the effect of low pH
      on DNA relaxation. Bacteria expressing novobiocin-resistant (NovR ) derivatives
      of gyrase or topo IV also exhibited DNA relaxation at acid pH, although further
      relaxation with novobiocin was not seen in the strain with NovR gyrase. Thus,
      inhibition of the negative supercoiling activity of gyrase was the primary cause
      of enhanced DNA relaxation in drug-treated bacteria. The Salmonella cytosol
      reaches pH 5-6 in response to an external pH of 4-5: the ATP-dependent DNA
      supercoiling activity of purified gyrase was progressively inhibited by lowering
      the pH in this range, as was the ATP-dependent DNA relaxation activity of topo
      IV. We propose that DNA relaxation in Salmonella within macrophage is due to acid
      mediated impairment of the negative supercoiling activity of gyrase.

PMID- 29352746
TI  - The common bean COK-4 and the Arabidopsis FER kinase domain share similar
      functions in plant growth and defence.
AB  - Receptor-like kinases are membrane proteins that can be shared by diverse
      signalling pathways. Among them, the Arabidopsis thaliana FERONIA (FER) plays a
      role in the balance between distinct signals to control growth and defence. We
      have found that COK-4, a putative kinase encoded in the common bean anthracnose
      resistance locus Co-4, which is transcriptionally regulated during the immune
      response, is highly similar to the kinase domain of FER. To assess whether COK-4
      is a functional orthologue of FER, we expressed COK-4 in the wild-type Col-0 and
      the fer-5 mutant of Arabidopsis and evaluated FER-associated traits. We observed
      that fer-5 plants show an enhanced apoplastic and stomatal defence against
      Pseudomonas syringae. In addition, the fer-5 mutant shows reduced biomass,
      smaller guard cell size, greater number of stomata per leaf area, fewer leaves,
      faster transition to reproductive stage and lower seed weight per plant than the
      wild-type Col-0. Except for the stomatal complex length and number of stomata,
      COK-4 expression in fer-5 lines partially or completely rescued both defence and
      developmental defects of fer-5 to the wild-type level. Notably, COK-4 may have an
      additive effect to FER, as the expression of COK-4 in Col-0 resulted in enhanced
      defence and growth phenotypes in comparison with wild-type Col-0 plants.
      Altogether, these findings indicate that the common bean COK-4 shares at least
      some of the multiple functions of the Arabidopsis FER kinase domain, acting in
      both the induction of plant growth and regulation of plant defence.

PMID- 29352747
TI  - Clathrin and AP1 are required for apical sorting of glycosyl phosphatidyl
      inositol-anchored proteins in biosynthetic and recycling routes in Madin-Darby
      canine kidney cells.
AB  - Recently, studies in animal models demonstrate potential roles for clathrin and
      AP1 in apical protein sorting in epithelial tissue. However, the precise
      functions of these proteins in apical protein transport remain unclear. Here, we
      reveal mistargeting of endogenous glycosyl phosphatidyl inositol-anchored
      proteins (GPI-APs) and soluble secretory proteins in Madin-Darby canine kidney
      (MDCK) cells upon clathrin heavy chain or AP1 subunit knockdown (KD). Using a
      novel directional endocytosis and recycling assay, we found that these KD cells
      are not only affected for apical sorting of GPI-APs in biosynthetic pathway but
      also for their apical recycling and basal-to-apical transcytosis routes. The
      apical distribution of the t-SNARE syntaxin 3, which is known to be responsible
      for selective targeting of various apical-destined cargo proteins in both
      biosynthetic and endocytic routes, is compromised suggesting a molecular
      explanation for the phenotype in KD cells. Our results demonstrate the importance
      of biosynthetic and endocytic routes for establishment and maintenance of apical
      localization of GPI-APs in polarized MDCK cells.

PMID- 29352748
TI  - Use of e-learning in clinical clerkships: effects on acquisition of
      dermatological knowledge and learning processes.
AB  - Objectives: To obtain a deeper understanding of how the e-learning program,
      Education in Dermatology (ED), affects the acquisition of dermatological
      knowledge and the underlying learning processes of medical students in their
      clinical phase. Methods: The study used a mixed method design with a convergent
      parallel collection of data. Medical students (n=62) from Maastricht University
      (The Netherlands) were randomized to either a conventional teaching group
      (control group n=30) or conventional teaching plus the e-learning program
      (application on smartphone) group (e-learning group n=32). Pre- and post
      intervention knowledge test results were analysed using an independent t-test.
      Individual semi-structured interviews (n=9) were conducted and verbatim
      transcribed recordings were analysed using King's template analysis. Results: The
      e-learning program positively influenced students' level of knowledge and their
      process of learning. A significant difference was found in the post-test scores
      for the control group (M=51.4, SD=6.43) and the e-learning group (M=73.09,
      SD=5.12); t(60)=-14.75, p<0.000). Interview data showed that the e-learning
      program stimulated students' learning as the application promoted the
      identification and recognition of skin disorders, the use of references, creation
      of documents and sharing information with colleagues. Conclusions: This study
      demonstrated that use of the e-learning program led to a significant improvement
      in basic dermatological knowledge. The underlying learning processes indicated
      that e-learning programs in dermatology filled a vital gap in the understanding
      of clinical reasoning in dermatology. These results might be useful when
      developing (clinical) teaching formats with a special focus on visual
      disciplines.

PMID- 29352749
TI  - Tips for optimizing organ preservation solutions.
AB  - Organ injury during ischemia is one of the clinical problems of today's
      transplantation. It occurs during warm ischemia time (WIT) when the blood flow is
      cut off and during cold ischemia when a graft is chilled in situ until the
      circulation is restored to the recipient organism. Fast cooling of the organ
      slows down metabolism and activates intracellular enzymes, which minimizes the
      effects of warm ischemia. Unfortunately, hypothermia also results in inhibition
      of ATP synthesis, cell swelling and intracellular acidity. That is why research
      is continually being conducted to develop new fluids for rinsing and storing
      organs, as well as to optimize the composition of those that are already in use,
      which will allow for longer and more effective graft storage and restoration of
      their optimal functions after transplantation. This article provides current
      information on rinsing and storage fluids available on the global market. It also
      discusses tips for the fluid modifications with hormones and micronutrients.

PMID- 29352750
TI  - Histomorphological analysis of the variability of the human skeleton: forensic
      implications.
AB  - One of the fundamental questions in forensic medicine and anthropology is whether
      or not a bone or bone fragment is human. Surprisingly at times for the extreme
      degradation of the bone (charred, old), DNA cannot be successfully performed and
      one must turn to other methods. Histological analysis at times can be proposed.
      However, the variability of a single human skeleton has never been tested. Forty
      nine thin sections of long, flat, irregular and short bones were obtained from a
      well-preserved medieval adult human skeleton. A qualitative histomorphological
      analysis was performed in order to assess the presence of primary and secondary
      bone and the presence, absence and orientation of vascular canals. No
      histological sections exhibited woven or fibro-lamellar bone. Long bones showed a
      higher variability with an alternation within the same section of areas
      characterized by tightly packed secondary osteons and areas with scattered
      secondary osteons immersed in a lamellar matrix. Flat and irregular bones
      appeared to be characterized by a greater uniformity with scattered osteons in
      abundant interstitial lamellae. Some cases of "osteon banding" and "drifting
      osteons" were observed. Although Haversian bone represent the most frequent
      pattern, a histomorphological variability between different bones of the same
      individual, in different portions of the same bone, and in different parts of the
      same section has been observed. Therefore, the present study has highlighted the
      importance of extending research to whole skeletons without focusing only on
      single bones, in order to have a better understanding of the histological
      variability of both human and non-human bone.

PMID- 29352752
TI  - Letter to the Editor: Influence of Intestinal Microbiota on Body Weight Gain: a
      Narrative Review of the Literature.

PMID- 29352751
TI  - Surgical management for a huge presacral teratoma and a meningocele in an adult
      with Currarino triad: a case report.
AB  - BACKGROUND: The Currarino triad is a rare hereditary syndrome comprising
      anorectal malformation, sacral bony defect, and presacral mass. Most of the
      patients are diagnosed during infancy. CASE PRESENTATION: A 44-year-old man was
      diagnosed with Currarino triad, with a huge presacral teratoma and meningocele.
      One-stage surgery via posterior approach was successful. CONCLUSIONS: Treatment
      of the presacral mass in the Currarino triad, diagnosed in adulthood, is
      challenging. Multidisciplinary management and detailed planning before surgery
      are important for a satisfactory outcome.

PMID- 29352753
TI  - Factors Predicting Length of Stay Following Bariatric Surgery: Retrospective
      Review of a Single UK Tertiary Centre Experience.
AB  - BACKGROUND: Laparoscopic Roux Y gastric bypass (RYGB) and laparoscopic sleeve
      gastrectomy (LSG) are the most commonly performed bariatric procedures.
      Improvement in techniques and perioperative management of patients have resulted
      in shorter hospital stay and reduced overall costs. Many post-operative protocols
      aspire to post-operative day 1 discharge with studies showing reduction in length
      of stay without increasing complications. In this study, we investigate the
      factors predictive of early discharge at our high-volume bariatric centre.
      METHODS: A retrospective review of all patients who underwent bariatric surgery
      (RYGB or SG) at a single centre between January 2013 and December 2014 was
      undertaken. Routine preoperative investigations were performed and patient
      discussed at bariatric MDT. Post-operative management was as per standard
      protocols. Demographic data, type of surgery and post-operative data (length of
      stay, complications, readmission, reoperations) were analysed. Statistical
      analysis was performed using SPSS. RESULTS: Five hundred six patients underwent
      RYGB (407 (80.4%)) or SG (99 (19.6%)). The mean preoperative BMI was 45.9 (range
      33.3-80.6). The median length of stay was 1 day (range 1-214 days; interquartile
      range 1-2 days) for RYGB and 2 days (range 1-8 days; interquartile range 1-3
      days) for SG. Two hundred sixty-eight (52.9%) patients were discharged on post
      operative day 1. The type of surgery and preoperative BMI were the only
      significant factors predicative of day 1 discharge after surgery. Patients
      undergoing SG were 3.3 times more likely to stay longer than 1 day after surgery
      (p < 0.001). BMI < 50 is associated with day 1 discharge (p = 0.030). CONCLUSION:
      Early discharge, on post-operative day 1 appears to be safe and is not associated
      with a greater risk of readmission. Sleeve gastrectomy and a BMI > 50 are
      associated with an increased risk of failure to achieve day 1 discharge.

PMID- 29352754
TI  - Providing Ethical Healthcare in Resource-Poor Environments.
AB  - The ethics of providing health care in resource-poor environments is a complex
      topic. It implies two related questions: What can we do with the resources on
      hand? Of all the things we can do, which ones should we do? "Resource-poor"
      (i.e., resource-challenged, resource-constrained) environments are situations in
      which clinicians, organizations, or healthcare systems have the knowledge and
      skills, but not the means, to carry out highly effective and beneficial
      interventions. Determinants of a population's health often rely less on disease
      and injury management than on recognizing and meeting their basic needs. Many of
      the world's people with the greatest health problems live in fragile contexts and
      remote areas. Their access to food, safe water, personal safety, improved
      sanitation facilities, and health care remains elusive, with availability often
      based on socioeconomic status, gender, ethnicity, or geography. Of course,
      ethical international healthcare work also requires an understanding of the
      illnesses and injuries that most frequently plague the population. To function
      ethically and to know both what can and what should be done with available
      resources, individuals and organizations involved in international healthcare
      must be experienced, adaptable, culturally sensitive, inspired, situationally
      aware, beneficent, courageous, honest, and fair.

PMID- 29352755
TI  - A Mos1 transposase in vivo assay to screen new HIV-1 integrase inhibitors.
AB  - The integrase and transposase enzymes of retrovirus and transposons,
      respectively, share the catalytic DDE domain. In vitro assays showed that
      inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase.
      Using a Drosophila strain in which the mobilisation of the mariner element can be
      quantified by mosaic eyes, we showed that flies maintained in medium containing
      210 uM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1
      integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation
      in mosaic eyes when treated with raltegravir and 28-32% when treated with
      dolutegravir. The gene expression of the mariner transposase gene, estimated by
      qPCR, is similar among treated and control flies. The results suggest that in
      vivo assays using Drosophila can be used as a primary screening of inhibitory
      drugs for transposase and retroviral integrase. The advantages of this assay are
      that it is easy, quick, cheap and is an in vivo test, meaning that the tested
      substance has to have been taken in by cells and has arrived at the target site,
      which is not the case when in vitro assays are applied.

PMID- 29352756
TI  - Influence of defect locations and nitrogen doping configurations on the
      mechanical properties of armchair graphene nanoribbons.
AB  - The effect of defect locations on the mechanical properties of armchair graphene
      nanoribbons (AGNRs) and the various configurations of nitrogen (N) doping on the
      mechanical properties of AGNRs were examined using molecular dynamics (MD)
      simulations. The variation of the Young's modulus (YM) and the ultimate tensile
      strength (UTS) of pyridinic-N, graphitic-N, and pyrrolic-N by increasing the
      concentration of N doping was investigated. The results of MD simulations show
      that the defect location has a significant effect on the UTS and failure strain
      (FS) of AGNRs in both vertical and horizontal directions. In the horizontal
      direction, variations of the UTS and FS are lower than in the vertical direction.
      On the other hand, the variations of the YM is almost similar in vertical and
      horizontal directions. The results of this work indicate that the UTS and FS of
      AGNRs are more sensitive than the YM of AGNRs for different defect directions.
      Pyridinic-N improves the mechanical properties of the defective AGNR and performs
      better YM and UTS values than the graphitic-N. Substitution N atoms, which are
      located at the defective sites and/or at the edges of AGNRs, are mechanically
      more favorable. Pyrrolic-N configuration has the lowest mechanical properties
      among the other configurations. Furthermore, pyrrolic-N with Stone-Wales-1 (SW-1)
      type of defect has higher mechanical properties than pyrrolic-N with Stone-Wales
      2 (SW-2) type of defect.

PMID- 29352757
TI  - Refractory Heartburn: A Challenging Problem in Clinical Practice.
AB  - Gastroesophageal reflux disease (GERD) is a condition which develops when the
      reflux of stomach contents causes troublesome symptoms and/or complications.
      Heartburn and regurgitation are the typical symptoms of GERD. The treatment of
      GERD encompasses lifestyle modifications, pharmacological, endoscopic, and
      surgical therapy. The majority of the patients respond to 4-8 weeks of proton
      pump inhibitors therapy, but 20-42% will demonstrate partial or complete lack of
      response to treatment. While these patients have been considered as having
      refractory heartburn, a subset of them does not have GERD or have not been
      adequately treated. The main causes of refractory heartburn include: poor
      compliance; inadequate proton-pump inhibitors dosage; incorrect diagnosis;
      comorbidities; genotypic differences; residual gastroesophageal reflux;
      eosinophilic esophagitis and others. Treatment is commonly directed toward the
      underlying cause of patients' refractory heartburn.

PMID- 29352761
TI  - Reply.

PMID- 29352759
TI  - Regional myocardial function abnormalities are associated with macro- and
      microcirculation dysfunction in the metabolic syndrome: the RESOLVE study.
AB  - Abnormalities in myocardial and vascular function have been reported in the
      metabolic syndrome (MetS), but whether these alterations are related remains
      poorly documented. Our aim was accordingly to investigate interrelationships
      between macro- and microcirculatory vasoreactivity and left ventricular (LV)
      myocardial function in MetS patients. Eighty-eight MetS individuals and 44 age-
      and gender-matched healthy controls were enrolled. LV global longitudinal strain
      (GLS) was measured using Vector Velocity Imaging. Endothelial-dependent and
      independent reactivity in macro- and microcirculatory territories was established
      using flow-mediated dilation and nitrate-mediated dilation of the brachial artery
      and cutaneous blood flow measured with laser Doppler flowmetry in response to
      iontophoresis of acetylcholine and sodium nitroprusside, respectively. Carotid
      intima-media thickness (cIMT) was measured according to the Mannheim consensus.
      Compared to controls, MetS patients presented with reduced GLS (p < 0.001)
      increased cIMT and impaired (p < 0.001) endothelial and smooth muscle function of
      the brachial artery and the forearm skin microcirculation. Highly significant
      relationships (p < 0.01) were noticed between GLS and vascular outcomes. In
      addition, cIMT (beta = 0.21, p = 0.024) and microcirculatory endothelium
      dependent reactivity (beta = - 0.20, p = 0.035) were identified as independent
      predictors of GLS. In MetS, abnormalities in myocardial function and endothelial
      as well as smooth muscle function of small and large arteries co-exist and are
      closely associated. This study supports a role for microvascular dysfunction in
      the pathogenesis of LV myocardial dysfunction.

PMID- 29352758
TI  - [Arthroscopic rotator cuff surgery : New and established methods].
AB  - This present article summarizes established and current developments and aspects
      of rotator cuff surgery. Achieved milestones as well as current approaches are
      presented and assessed with respect to their clinical and radiographic impact.
      Despite biomechanical and technical improvements in modern rotator cuff repair
      techniques, re-defect and re-tearing rates could not be fully eliminated.
      Meanwhile, the importance of biological processes around successful tendon-bone
      reintegration has been increasingly recognized. Hence, this article presents the
      current scientific standing regarding biological growth factors, platelet-rich
      plasma and rotator cuff augmentation techniques (with allogenic/autologous
      grafts). In summary, there are clear biomechanical advantages as well as many
      promising approaches to biological augmentation; however, the latter have not yet
      been transferred into regular clinical application.

PMID- 29352760
TI  - Endothelial function estimated by digital reactive hyperemia in patients with
      atherosclerotic risk factors or coronary artery disease.
AB  - Due to the complex profile of atherosclerotic risk factors, an integrated
      analysis of a specific individual is difficult. Endothelial function reflects a
      composite of various risk factors, and may be used as an optimal tool to estimate
      the overall atherosclerotic risk. In this study, we investigated the value of
      digital Reactive Hyperemia Index (RHI) in an actual population with multiple
      atherosclerotic risk factors or coronary artery disease (CAD). A total of 417
      patients from the Seoul National University Boramae Medical Center RHI registry
      were enrolled in this study. Patients were enrolled from January, 2013 to July,
      2016. RHI was measured using the EndoPAT2000 system (Itamiar Medical Inc.
      Israel). The mean value of RHI was 1.67 +/- 0.48 in total study population. Among
      various atherosclerotic risk factors, RHI was significantly lower in older (> 60
      years) patients, diabetics, smokers' patients on statin therapy, and those with
      coronary or cerebrovascular disease. Most of these findings were consistent after
      adjustment with multiple regression analysis. RHI was significantly associated
      with CAD, with a hazard ratio of 1.80 (95% confidence interval 1.15-2.80, p =
      0.010). In the subgroup with CAD, current smoking was the only finding showing a
      lower RHI. Brachial-ankle pulse wave velocity, which is a surrogate marker of
      arterial atherosclerotic change, was not correlated with RHI in patients with
      clinically significant atherosclerotic disease. RHI was significantly reduced by
      major atherosclerotic risk factors and in clinical atherosclerotic disease. RHI
      may reflect a composite effect of risk factors pertaining to the endothelial
      function.

PMID- 29352762
TI  - Reply.

PMID- 29352763
TI  - Erratum.

PMID- 29352769
TI  - Resolvin E1, resolvin D1 and resolvin D2 inhibit constriction of rat thoracic
      aorta and human pulmonary artery induced by the thromboxane mimetic U46619.
AB  - BACKGROUND AND PURPOSE: The omega-6 fatty acid-derived lipid mediators such as
      prostanoids, thromboxane and leukotrienes have well-established roles in
      regulating both inflammation and smooth muscle contractility. Resolvins are
      derived from omega-3 fatty acids and have important roles in promoting the
      resolution of inflammation, but their activity on smooth muscle contractility is
      unknown. We investigated whether resolvin E1 (RvE1), resolvin D1 (RvD1) and
      resolvin D2 (RvD2) can modulate contractions of isolated segments of rat thoracic
      aorta (RTA) or human pulmonary artery (HPA) induced by the alpha1 -adrenoceptor
      agonist phenylephrine or the stable thromboxane A2 mimetic U46619. EXPERIMENTAL
      APPROACH: Contractile responses in RTA and HPA were measured using wire
      myography. Receptor expression was investigated by immunohistochemistry. KEY
      RESULTS: Constriction of RTA segments by U46619, but not by phenylephrine, was
      significantly inhibited by pretreatment for 1 or 24 h with 10-100 nM RvE1, RvD1
      or RvD2. The inhibitory effect of RvE1 was partially blocked by a chemerin
      receptor antagonist (CCX832). RvE1 at only 1-10 nM also significantly inhibited
      U46619-induced constriction of HPA segments, and the chemerin receptor, GPR32 and
      FPR2/ALX were identified in HPA smooth muscle. CONCLUSION AND IMPLICATIONS: These
      data suggest that resolvins or their mimetics may prove useful novel therapeutics
      in diseases such as pulmonary arterial hypertension, which are characterized by
      increased thromboxane contractile activity.

PMID- 29352770
TI  - Concentration-dependent effect of bleaching agents on the immunolabelling of
      interleukin-6, interleukin-17 and CD5-positive cells in the dental pulp.
AB  - AIM: To evaluate lymphocyte-like cell activation (CD5-positive cells) and the
      expression of interleukin (IL)-6 and IL-17 in the pulp after tooth bleaching with
      two concentrations of hydrogen peroxide (H2 O2 ). METHODOLOGY: The right and left
      maxillary molars from 40 rats were treated randomly with bleaching gel with 20%
      H2 O2 (BLUE group, 1 application of 50 min), 35% H2 O2 (MAXX group, three
      applications of 15 min), or placebo gel (control). After 2 and 30 days, the rats
      were killed (n = 10), and the jaws were processed for histological and
      immunohistochemistry analysis of the pulp tissue. The scores of inflammation and
      immunolabelling (IL-6/IL-17) were submitted to Mann-Whitney and Kruskal-Wallis
      followed Dunn tests, respectively; anova tests were used for comparisons of
      number of CD5-positive cells and pulp chamber area values (P < 0.05). RESULTS: At
      2 days, 60% of specimens of the BLUE group were associated with moderate
      inflammation in pulp horns, and in the MAXX group with necrosis (P < 0.05). At 30
      days, the pulp was organized, and tertiary dentine was formed. The MAXX group had
      superior immunolabelling of IL-17 at 2 days differing significantly from other
      groups (P < 0.05). At 2 days, 90% of the specimens of the BLUE group had moderate
      immunolabelling of IL-6, and 50% of the MAXX group had severe immunolabelling,
      both significantly different from the control (P < 0.05). There was no
      significant difference between the groups at 30 days (P > 0.05). CD5-positive
      cells were present at 2 and 30 days, particularly in the bleached groups (P <
      0.05), without significant difference between time periods (P > 0.05).
      CONCLUSIONS: IL-6 and IL-17 participated in inflammation in the pulp tissue of
      rats after tooth bleaching, particularly at 2 days. The immunolabelling was
      greater with increasing H2 O2 concentration. This process was accompanied by the
      prolonged activation of CD5-positive cells.

PMID- 29352771
TI  - Severe cutaneous adverse reactions due to inappropriate medication use.
AB  - BACKGROUND: The proportion of severe cutaneous adverse reactions (SCARs) that
      could be avoided if medication use was consistent with good medical practice is
      unknown. OBJECTIVES: To estimate the proportion of SCARs related to inappropriate
      medication use. METHODS: We carried out a retrospective study of all validated
      SCARs collected in a French registry between 2003 and 2016. For each case, all
      plausible drugs suspected of inducing SCARs (i.e. not just the drug regarded as
      'the most probable') were considered with regard to (i) prescription for an
      inappropriate indication, (ii) unintentional rechallenge despite a previous
      allergy to the drug or (iii) self-medication with prescription medicines.
      RESULTS: In total, 602 cases were included in the analyses. Antibiotics,
      anticonvulsants and allopurinol were the drugs most frequently involved,
      accounting for more than 50% of all cases. All suspected medications were
      considered to have been appropriately used for 417 of the 602 individuals
      included in the study population [69.3%, 95% confidence interval (CI) 65.6-73.0]
      and inappropriately used for 144 individuals (23.9%, 95% CI 20.5-27.3). These
      inappropriate uses were due mainly to prescriptions for an inappropriate
      indication (65.8%, 95% CI 58.4-73.2) or unintentional rechallenge (20.9%, 95% CI
      14.6-27.2). Allopurinol and co-trimoxazole were the drugs most frequently
      involved in inappropriate indications. Antibiotics were the largest group
      involved in unintentional rechallenge. Nonsteroidal anti-inflammatory drugs,
      available on prescription, were most frequently involved in inappropriate self
      medication. CONCLUSIONS: Our results underline the need for respecting the
      appropriate indication for drugs in order to reduce the incidence of SCARs.
      Reducing unintentional rechallenge also seems to be a necessary preventive
      measure.

PMID- 29352773
TI  - Ultra-fast relaxation, decoherence, and localization of photoexcited states in pi
      conjugated polymers.
AB  - The exciton relaxation dynamics of photoexcited electronic states in poly(p
      phenylenevinylene) are theoretically investigated within a coarse-grained model,
      in which both the exciton and nuclear degrees of freedom are treated quantum
      mechanically. The Frenkel-Holstein Hamiltonian is used to describe the strong
      exciton-phonon coupling present in the system, while external damping of the
      internal nuclear degrees of freedom is accounted for by a Lindblad master
      equation. Numerically, the dynamics are computed using the time evolving block
      decimation and quantum jump trajectory techniques. The values of the model
      parameters physically relevant to polymer systems naturally lead to a separation
      of time scales, with the ultra-fast dynamics corresponding to energy transfer
      from the exciton to the internal phonon modes (i.e., the C-C bond oscillations),
      while the longer time dynamics correspond to damping of these phonon modes by the
      external dissipation. Associated with these time scales, we investigate the
      following processes that are indicative of the system relaxing onto the emissive
      chromophores of the polymer: (1) Exciton-polaron formation occurs on an ultra
      fast time scale, with the associated exciton-phonon correlations present within
      half a vibrational time period of the C-C bond oscillations. (2) Exciton
      decoherence is driven by the decay in the vibrational overlaps associated with
      exciton-polaron formation, occurring on the same time scale. (3) Exciton density
      localization is driven by the external dissipation, arising from "wavefunction
      collapse" occurring as a result of the system-environment interactions. Finally,
      we show how fluorescence anisotropy measurements can be used to investigate the
      exciton decoherence process during the relaxation dynamics.

PMID- 29352772
TI  - Neurotransmitters and Receptors Changes in Medial Nucleus of the Trapezoid Body
      (MNTB) of Early-Developmental Rats with Single-Side Deafness.
AB  - BACKGROUND Congenital single-side deafness (SSD) affects sound localization even
      after cochlear implantation (CI) in some conditions. The medial nucleus of the
      trapezoid body (MNTB) plays an important role in binaural benefit and sound
      localization, but little is known about intrinsic molecular changes in MNTB with
      SSD. We aimed to observe changes in MNTB in early-developmental SSD rats,
      including the key neurotransmitters (GABA, Gly, Glu) and major receptors (GABAa
      R/GABAb-R for GABA, Gly-R for Gly, and AMPA/NMDA for Glu). MATERIAL AND METHODS
      The model of early-developmental SSD was acquired by right cochlear ablation at
      P12 and confirmed by ABR. High-performance liquid chromatography fluorescence
      detection (HPLC-FLD) was performed to measure the levels of neurotransmitters in
      MNTB. The relative expression of neurotransmitter receptors was tested by
      quantitative real-time PCR analysis. RESULTS (1) The right MNTB of experimental
      rats had an increase in GABA, Gly, and Glu at 4 weeks after right cochlear
      ablation (P<0.05). (2) At 2 weeks, the left MNTB of experimental rats showed
      increases in GABAa-R, GABAb-R, Gly-R, and AMPA, while the right MNTB showed lower
      expression of NMDA (P<0.05). The higher receptors in left MNTB decreased to a
      level at which we found no difference at 1 week for GABAa-R and GABAb-R (P>0.05),
      and was even reversed for Gly-R and AMPA (P<0.05). (3) Gly level was
      significantly increased at 2 weeks bilaterally and continued to 4 weeks in the
      left MNTB (P<0.05). CONCLUSIONS Early-developmental SSD can lead to asymmetric
      distribution of neurotransmitters and receptors in MNTB, which can be the
      fundamental cause of defective sound localization after cochlear implantation.

PMID- 29352774
TI  - The Bloch equation with terms induced by an electric field.
AB  - The Bloch equation of the nuclear magnetization of spin-1/2 nuclei in molecules,
      which have permanent electric dipole moments MUe that are placed simultaneously
      in a magnetic field B and an electric field E, is derived. It is shown that if
      the principal components of the nuclear magnetic shielding tensor sigma and the
      dipole moment MUe are known, then the measurement of the transverse component to
      the magnetic field B of the nuclear magnetization, which is induced by the
      application of the electric field oscillating at the half of the spin precession
      frequency, allows determining the orientation of the dipole moment MUe with
      respect to the principal axis system of the symmetric part of the tensor sigma.
      Four-component relativistic density functional theory computations, which have
      been performed for several molecules containing heavy nuclei, i.e., 207Pb, 205Tl,
      199Hg, 195Pt, and 125Te, indicate that coefficients of the relaxation matrix
      perturbed by the electric field E are in favorable cases of the order of 1000 pm2
      V-2 T-2. Therefore, the spin dynamics is perturbed at experimentally observable
      levels for the strengths of electric and magnetic fields E = 5 kV/mm and B = 10
      T, respectively.

PMID- 29352775
TI  - Converging many-body correlation energies by means of sequence extrapolation.
AB  - We present an extrapolation scheme for the correlation energy in many-body theory
      that requires only a relatively small fraction of the orbitals spanning the
      virtual space but recovers nearly the whole dynamic correlation energy,
      independently of the single- or multi-reference nature of the problem.
      Applications to both ground-state chemistry and photochemistry are discussed that
      clearly show how such an extrapolation scheme can be used to overcome the scaling
      walls in ab initio quantum chemistry arising from the sheer number of molecular
      orbitals needed for very accurate calculations.

PMID- 29352776
TI  - Plasma CVD of hydrogenated boron-carbon thin films from triethylboron.
AB  - Low-temperature chemical vapor deposition (CVD) of B-C thin films is of
      importance for neutron voltaics and semiconductor technology. The highly reactive
      trialkylboranes, with alkyl groups of 1-4 carbon atoms, are a class of precursors
      that have been less explored for low-temperature CVD of B-C films. Herein, we
      demonstrate plasma CVD of B-C thin films using triethylboron (TEB) as a single
      source precursor in an Ar plasma. We show that the film density and B/C ratio
      increases with increasing plasma power, reaching a density of 2.20 g/cm3 and B/C
      = 1.7. This is attributed to a more intense energetic bombardment during
      deposition and more complete dissociation of the TEB molecule in the plasma at
      higher plasma power. The hydrogen content in the films ranges between 14 and 20
      at. %. Optical emission spectroscopy of the plasma shows that BH, CH, C2, and H
      are the optically active plasma species from TEB. We suggest a plasma chemical
      model based on beta-hydrogen elimination of C2H4 to form BH3, in which BH3 and
      C2H4 are then dehydrogenated to form BH and C2H2. Furthermore, C2H2 decomposes in
      the plasma to produce C2 and CH, which together with BH and possibly BH3-x(C2H5)x
      are the film forming species.

PMID- 29352777
TI  - Perspective: Theory of quantum transport in molecular junctions.
AB  - Molecular junctions, where single molecules are bound to metal or semiconductor
      electrodes, represent a unique architecture to investigate molecules in a
      distinct nonequilibrium situation and, in a broader context, to study basic
      mechanisms of charge and energy transport in a many-body quantum system at the
      nanoscale. Experimental studies of molecular junctions have revealed a wealth of
      interesting transport phenomena, the understanding of which necessitates
      theoretical modeling. The accurate theoretical description of quantum transport
      in molecular junctions is challenging because it requires methods that are
      capable to describe the electronic structure and dynamics of molecules in a
      condensed phase environment out of equilibrium, in some cases with strong
      electron-electron and/or electronic-vibrational interaction. This perspective
      discusses recent progress in the theory and simulation of quantum transport in
      molecular junctions. Furthermore, challenges are identified, which appear crucial
      to achieve a comprehensive and quantitative understanding of transport in these
      systems.

PMID- 29352778
TI  - Continuum percolation of polydisperse rods in quadrupole fields: Theory and
      simulations.
AB  - We investigate percolation in mixtures of nanorods in the presence of external
      fields that align or disalign the particles with the field axis. Such conditions
      are found in the formulation and processing of nanocomposites, where the field
      may be electric, magnetic, or due to elongational flow. Our focus is on the
      effect of length polydispersity, which-in the absence of a field-is known to
      produce a percolation threshold that scales with the inverse weight average of
      the particle length. Using a model of non-interacting spherocylinders in
      conjunction with connectedness percolation theory, we show that a quadrupolar
      field always increases the percolation threshold and that the universal scaling
      with the inverse weight average no longer holds if the field couples to the
      particle length. Instead, the percolation threshold becomes a function of higher
      moments of the length distribution, where the order of the relevant moments
      crucially depends on the strength and type of field applied. The theoretical
      predictions compare well with the results of our Monte Carlo simulations, which
      eliminate finite size effects by exploiting the fact that the universal scaling
      of the wrapping probability function holds even in anisotropic systems. Theory
      and simulation demonstrate that the percolation threshold of a polydisperse
      mixture can be lower than that of the individual components, confirming recent
      work based on a mapping onto a Bethe lattice as well as earlier computer
      simulations involving dipole fields. Our work shows how the formulation of
      nanocomposites may be used to compensate for the adverse effects of aligning
      fields that are inevitable under practical manufacturing conditions.

PMID- 29352779
TI  - Hydrodynamically Coupled Brownian Dynamics: A coarse-grain particle-based
      Brownian dynamics technique with hydrodynamic interactions for modeling self
      developing flow of polymer solutions.
AB  - We present a novel coarse-grain particle-based simulation technique for modeling
      self-developing flow of dilute and semi-dilute polymer solutions. The central
      idea in this paper is the two-way coupling between a mesoscopic polymer model and
      a phenomenological fluid model. As our polymer model, we choose Responsive
      Particle Dynamics (RaPiD), a Brownian dynamics method, which formulates the so
      called "conservative" and "transient" pair-potentials through which the polymers
      interact besides experiencing random forces in accordance with the fluctuation
      dissipation theorem. In addition to these interactions, our polymer blobs are
      also influenced by the background solvent velocity field, which we calculate by
      solving the Navier-Stokes equation discretized on a moving grid of fluid blobs
      using the Smoothed Particle Hydrodynamics (SPH) technique. While the polymers
      experience this frictional force opposing their motion relative to the background
      flow field, our fluid blobs also in turn are influenced by the motion of the
      polymers through an interaction term. This makes our technique a two-way coupling
      algorithm. We have constructed this interaction term in such a way that momentum
      is conserved locally, thereby preserving long range hydrodynamics. Furthermore,
      we have derived pairwise fluctuation terms for the velocities of the fluid blobs
      using the Fokker-Planck equation, which have been alternatively derived using the
      General Equation for the Non-Equilibrium Reversible-Irreversible Coupling
      (GENERIC) approach in Smoothed Dissipative Particle Dynamics (SDPD) literature.
      These velocity fluctuations for the fluid may be incorporated into the velocity
      updates for our fluid blobs to obtain a thermodynamically consistent distribution
      of velocities. In cases where these fluctuations are insignificant, however,
      these additional terms may well be dropped out as they are in a standard SPH
      simulation. We have applied our technique to study the rheology of two different
      concentrations of our model linear polymer solutions. The results show that the
      polymers and the fluid are coupled very well with each other, showing no lag
      between their velocities. Furthermore, our results show non-Newtonian shear
      thinning and the characteristic flattening of the Poiseuille flow profile
      typically observed for polymer solutions.

PMID- 29352780
TI  - Hydrogen collisions with transition metal surfaces: Universal electronically
      nonadiabatic adsorption.
AB  - Inelastic scattering of H and D atoms from the (111) surfaces of six fcc
      transition metals (Au, Pt, Ag, Pd, Cu, and Ni) was investigated, and in each
      case, excitation of electron-hole pairs dominates the inelasticity. The results
      are very similar for all six metals. Differences in the average kinetic energy
      losses between metals can mainly be attributed to different efficiencies in the
      coupling to phonons due to the different masses of the metal atoms. The
      experimental observations can be reproduced by molecular dynamics simulations
      based on full-dimensional potential energy surfaces and including electronic
      excitations by using electronic friction in the local density friction
      approximation. The determining factors for the energy loss are the electron
      density at the surface, which is similar for all six metals, and the mass ratio
      between the impinging atoms and the surface atoms. Details of the electronic
      structure of the metal do not play a significant role. The experimentally
      validated simulations are used to explore sticking over a wide range of incidence
      conditions. We find that the sticking probability increases for H and D
      collisions near normal incidence-consistent with a previously reported
      penetration-resurfacing mechanism. The sticking probability for H or D on any of
      these metals may be represented as a simple function of the incidence energy,
      Ein, metal atom mass, M, and incidence angle, ??in. S=(S0+a?Ein+b?M)*(1-h(??in
      c)(1-cos(??in-c)d?h(Ein-e)(Ein-e))), where h is the Heaviside step function and
      for H, S0 = 1.081, a = -0.125 eV-1, b=-8.40?10-4 u-1, c = 28.88 degrees , d =
      1.166 eV-1, and e = 0.442 eV; whereas for D, S0 = 1.120, a = -0.124 eV-1, b=
      1.20?10-3 u-1, c = 28.62 degrees , d = 1.196 eV-1, and e = 0.474 eV.

PMID- 29352781
TI  - Analysis of the anomalous mean-field like properties of Gaussian core model in
      terms of entropy.
AB  - Studies of the Gaussian core model (GCM) have shown that it behaves like a mean
      field model and the properties are quite different from standard glass former. In
      this work, we investigate the entropies, namely, the excess entropy (Sex) and the
      configurational entropy (Sc) and their different components to address these
      anomalies. Our study corroborates most of the earlier observations and also sheds
      new light on the high and low temperature dynamics. We find that unlike in
      standard glass former where high temperature dynamics is dominated by two-body
      correlation and low temperature by many-body correlations, in the GCM both high
      and low temperature dynamics are dominated by many-body correlations. We also
      find that the many-body entropy which is usually positive at low temperatures and
      is associated with activated dynamics is negative in the GCM suggesting
      suppression of activation. Interestingly despite the suppression of activation,
      the Adam-Gibbs (AG) relation that describes activated dynamics holds in the GCM,
      thus suggesting a non-activated contribution in AG relation. We also find an
      overlap between the AG relation and mode coupling power law regime leading to a
      power law behavior of Sc. From our analysis of this power law behavior, we
      predict that in the GCM the high temperature dynamics will disappear at dynamical
      transition temperature and below that there will be a transition to the activated
      regime. Our study further reveals that the activated regime in the GCM is quite
      narrow.

PMID- 29352782
TI  - Communication: Investigation of ion aggregation in ionic liquids and their
      solutions with lithium salt under high pressure.
AB  - X-ray scattering measurements were utilized to probe the effects of pressure on a
      series of ionic liquids, N-alkyl-N-methyl-pyrrolidinium
      bis(trifluoromethanesulfonyl)imide (Pyr1A-TFSI) (A = 3, 6, and 9), along with
      mixtures of ionic liquid and 30 mol. % lithium bis(trifluoromethanesulfonyl)imide
      (LiTFSI) salt. No evidence was found for crystallization of the pure ionic
      liquids or salt mixtures even at pressures up to 9.2 GPa. No phase separation or
      demixing was observed for the ionic liquid and salt mixtures. Shifts in the peak
      positions are indicative of compression of the ionic liquids and mixtures up to 2
      GPa, after which samples reach a region of relative incompressibility, possibly
      indicative of a transition to a glassy state. With the application of pressure,
      the intensity of the prepeak was found to decrease significantly, indicating a
      reduction in cation alkyl chain aggregation. Additionally, incompressibility of
      the scattering peak associated with the distance between like-charges in the pure
      ionic liquids compared to that in mixtures with lithium salt suggests that the
      application of pressure could inhibit Li+ coordination with TFSI- to form
      Li[TFSI2]- complexes. This inhibition occurs through the suppression of TFSI- in
      the trans conformer, in favor of the smaller cis conformer, at high pressures.

PMID- 29352783
TI  - Addressing global uncertainty and sensitivity in first-principles based
      microkinetic models by an adaptive sparse grid approach.
AB  - In the last decade, first-principles-based microkinetic modeling has been
      developed into an important tool for a mechanistic understanding of heterogeneous
      catalysis. A commonly known, but hitherto barely analyzed issue in this kind of
      modeling is the presence of sizable errors from the use of approximate Density
      Functional Theory (DFT). We here address the propagation of these errors to the
      catalytic turnover frequency (TOF) by global sensitivity and uncertainty
      analysis. Both analyses require the numerical quadrature of high-dimensional
      integrals. To achieve this efficiently, we utilize and extend an adaptive sparse
      grid approach and exploit the confinement of the strongly non-linear behavior of
      the TOF to local regions of the parameter space. We demonstrate the methodology
      on a model of the oxygen evolution reaction at the Co3O4 (110)-A surface, using a
      maximum entropy error model that imposes nothing but reasonable bounds on the
      errors. For this setting, the DFT errors lead to an absolute uncertainty of
      several orders of magnitude in the TOF. We nevertheless find that it is still
      possible to draw conclusions from such uncertain models about the atomistic
      aspects controlling the reactivity. A comparison with derivative-based local
      sensitivity analysis instead reveals that this more established approach provides
      incomplete information. Since the adaptive sparse grids allow for the evaluation
      of the integrals with only a modest number of function evaluations, this approach
      opens the way for a global sensitivity analysis of more complex models, for
      instance, models based on kinetic Monte Carlo simulations.

PMID- 29352784
TI  - Calculation of a solid/liquid surface tension: A methodological study.
AB  - The surface tension of a model solid/liquid interface constituted of a graphene
      sheet surrounded by liquid methane has been computed using molecular dynamics in
      the Kirkwood-Buff formalism. We show that contrary to the fluid/fluid case, the
      solid/liquid case can lead to different structurations of the first fluid layer,
      leading to significantly different values of surface tension. Therefore we
      present a statistical approach that consists in running a series of molecular
      simulations of similar systems with different initial conditions, leading to a
      distribution of surface tensions from which an average value and uncertainty can
      be extracted. Our results suggest that these distributions converge as the system
      size increases. Besides we show that surface tension is not particularly
      sensitive to the choice of the potential energy cutoff and that long-range
      corrections can be neglected contrary to what we observed in the liquid/vapour
      interfaces. We have not observed the previously reported commensurability effect.

PMID- 29352785
TI  - Markov-state model for CO2 binding with carbonic anhydrase under confinement.
AB  - Enzyme immobilization with a nanostructure material can enhance its stability and
      facilitate reusability. However, the apparent activity is often compromised due
      to additional diffusion barriers and complex interactions with the substrates and
      solvent molecules. The present study elucidates the effects of the surface
      hydrophobicity of nano-confinement on CO2 diffusion to the active site of human
      carbonic anhydrase II (CA), an enzyme that is able to catalyze CO2 hydration at
      extremely high turnover rates. Using the Markov-state model in combination with
      coarse-grained molecular dynamics simulations, we demonstrate that a hydrophobic
      cage increases CO2 local density but hinders its diffusion towards the active
      site of CA under confinement. By contrast, a hydrophilic cage hinders CO2
      adsorption but promotes its binding with CA. An optimal surface hydrophobicity
      can be identified to maximize both the CO2 occupation probability and the
      diffusion rate. The simulation results offer insight into understanding enzyme
      performance under nano-confinement and help us to advance broader applications of
      CA for CO2 absorption and recovery.

PMID- 29352786
TI  - From elemental tellurium to Ge2Sb2Te5 melts: High temperature dynamic and
      relaxation properties in relationship with the possible fragile to strong
      transition.
AB  - We investigate the dynamic properties of Ge-Sb-Te phase change melts using first
      principles molecular dynamics with a special emphasis on the effect of tellurium
      composition on melt dynamics. From structural models and trajectories established
      previously [H. Flores-Ruiz et al., Phys. Rev. B 92, 134205 (2015)], we calculate
      the diffusion coefficients for the different species, the activation energies for
      diffusion, the Van Hove correlation, and the intermediate scattering functions
      able to substantiate the dynamics and relaxation behavior of the liquids as a
      function of temperature and composition that is also compared to experiment
      whenever possible. We find that the diffusion is mostly Arrhenius-like and that
      the addition of Ge/Sb atoms leads to a global decrease of the jump probability
      and to an increase in activated dynamics for diffusion. Relaxation behavior is
      analyzed and used in order to evaluate the possibility of a fragile to strong
      transition that is evidenced from the calculated high fragility (M = 129) of
      Ge2Sb2Te5 at high temperatures.

PMID- 29352787
TI  - Communication: Exact analytical derivatives for the domain-based local pair
      natural orbital MP2 method (DLPNO-MP2).
AB  - Electron correlation methods based on pair natural orbitals (PNOs) have gained an
      increasing degree of interest in recent years, as they permit energy calculations
      to be performed on systems containing up to many hundred atoms, while maintaining
      chemical accuracy for reaction energies. We present an approach for taking exact
      analytical first derivatives of the energy contributions in the simplest method
      of the family of Domain-based Local Pair Natural Orbital (DLPNO) methods, closed
      shell DLPNO-MP2. The Lagrangian function contains constraints to account for the
      relaxation of PNOs. RI-MP2 reference geometries are reproduced accurately, as
      exemplified for four systems with a substantial degree of nonbonding
      interactions. By the example of electric field gradients, we demonstrate that
      omitting PNO-specific constraints can lead to dramatic errors for orbital-relaxed
      properties.

PMID- 29352788
TI  - Formic acid dimers in a nitrogen matrix.
AB  - Formic acid (HCOOH) dimers are studied by infrared spectroscopy in a nitrogen
      matrix and by ab initio calculations. We benefit from the use of a nitrogen
      matrix where the lifetime of the higher-energy (cis) conformer is very long (~11
      h vs. 7 min in an argon matrix). As a result, in a nitrogen matrix, a large
      proportion of the cis conformer can be produced by vibrational excitation of the
      lower-energy (trans) conformer. Three trans-trans, four trans-cis, and three cis
      cis dimers are found in the experiments. The spectroscopic information on most of
      these dimers is enriched compared to the previous studies in an argon matrix. The
      cis-cis dimers of ordinary formic acid (without deuteration) are reported here
      for the first time. Several conformational processes are obtained using selective
      excitation by infrared light, some of them also for the first time. In
      particular, we report on the formation of cis-cis dimers upon vibrational
      excitation of trans-cis dimers. Tunneling decays of several dimers have been
      detected in the dark. The tunneling decay of cis-cis dimers of formic acid as
      well as the stabilization of cis units in cis-cis dimers is also observed for the
      first time.

PMID- 29352789
TI  - Hydrodynamic relaxations in dissipative particle dynamics.
AB  - This paper studies the dynamics of relaxation phenomena in the standard
      dissipative particle dynamics (DPD) model [R. D. Groot and P. B. Warren, J. Chem.
      Phys. 107, 4423 (1997)]. Using fluctuating hydrodynamics as the framework of the
      investigation, we focus on the collective transverse and longitudinal dynamics.
      It is shown that classical hydrodynamic theory predicts the transverse dynamics
      at relatively low temperatures very well when compared to simulation data;
      however, the theory predictions are, on the same length scale, less accurate for
      higher temperatures. The agreement with hydrodynamics depends on the definition
      of the viscosity, and here we find that the transverse dynamics are independent
      of the dissipative and random shear force contributions to the stress. For high
      temperatures, the spectrum for the longitudinal dynamics is dominated by the
      Brillouin peak for large length scales and the relaxation is therefore governed
      by sound wave propagation and is athermal. This contrasts the results at lower
      temperatures and small length scale, where the thermal process is clearly present
      in the spectra. The DPD model, at least qualitatively, re-captures the underlying
      hydrodynamical mechanisms, and quantitative agreement is excellent at
      intermediate temperatures for the transverse dynamics.

PMID- 29352790
TI  - On the theoretical prediction of fluorescence rates from first principles using
      the path integral approach.
AB  - In this work, we present and implement the theory for calculating fluorescence
      rates and absorption and emission spectra from first principles, using the path
      integral approach. We discuss some approximations and modifications to the full
      set of equations that improve speed and numerical stability for the case when a
      large number of modes are considered. New methods to approximate the excited
      state potential energy surface are also discussed and it is shown that for most
      purposes, these can be used instead of a full geometry optimization to obtain the
      rates mentioned above. A few examples are presented and the overall performance
      of the method is discussed. It is shown that the rates and spectra computed in
      this way are well within the acceptable range of errors and can be used in future
      predictions, particularly for screening purposes, with the only limitation on
      size being that of the electronic structure calculation itself.

PMID- 29352791
TI  - Kohn-Sham potentials from electron densities using a matrix representation within
      finite atomic orbital basis sets.
AB  - We revisit the static response function-based Kohn-Sham (KS) inversion procedure
      for determining the KS effective potential that corresponds to a given target
      electron density within finite atomic orbital basis sets. Instead of expanding
      the potential in an auxiliary basis set, we directly update the potential in its
      matrix representation. Through numerical examples, we show that the reconstructed
      density rapidly converges to the target density. Preliminary results are
      presented to illustrate the possibility of obtaining a local potential in real
      space from the optimized potential in its matrix representation. We have further
      applied this matrix-based KS inversion approach to density functional embedding
      theory. A proof-of-concept study of a solvated proton transfer reaction
      demonstrates the method's promise.

PMID- 29352792
TI  - Relationship between global and segmental dynamics of poly(butylene oxide)
      studied by broadband dielectric spectroscopy.
AB  - Relationship between segmental relaxation and normal-mode relaxation has been
      studied for molten poly(butylene oxide)s having various molecular weights by
      broadband dielectric spectroscopy over a wide temperature (T) range. We found
      that T dependence of the segmental relaxation time, taus, was weaker than the
      normal mode time, taun, at high T(>250 K ~ Tg + 50 K), and the taun/taus ratio
      systematically decreased with increasing temperature. This high temperature
      complexity, whose mechanism has not been discussed in detail so far, was
      quantitatively explained by assuming the two step processes: local conformation
      change of polymers (elementary process) occurs first, and then the motion of a
      segment unit (second process) occurs. It was also found that the elementary
      process was strongly correlated with the experimentally observed beta-relaxation.

PMID- 29352793
TI  - Theoretical study of tetrahedral site occupation by hydrogen in Pd nanoparticles.
AB  - To understand the enhanced effects and new hydrogen absorption properties of
      metal nanoparticles, we theoretically investigated the hydrogen absorption in Pd
      nanoparticles, adopting the Pd405 model of ca. 2.5 nm by using density functional
      theory. Pd405 showed inhomogeneous geometric features, especially near the
      surface region. The hydrogen absorptions in octahedral (O) and tetrahedral (T)
      sites near the core region were stable and unstable, respectively, similar to the
      Pd bulk. We clearly demonstrated the possibility of hydrogen absorption in T
      sites near the surface of Pd405. The flexible volume change and the difference in
      hydrogen position relative to the center of mass of the T site that we observed
      are important factors for stable hydrogen absorption in T sites of Pd
      nanoparticles. In addition, we discuss the differences in hydrogen diffusion
      mechanisms in the core and near surface regions, based on the stability of
      hydrogen absorption in O and T sites.

PMID- 29352795
TI  - Impact of surface energy on the shock properties of granular explosives.
AB  - This paper presents the first part of a two-fold molecular dynamics study of the
      impact of the granularity on the shock properties of high explosives. Recent
      experimental studies show that the granularity can have a substantial impact on
      the properties of detonation products {i.e., variations in the size distributions
      of detonation nanodiamonds [V. Pichot et al., Sci. Rep. 3, 2159 (2013)]}. These
      variations can have two origins: the surface energy, which is a priori enhanced
      from micro- to nano-scale, and the porosity induced by the granular structure. In
      this first report, we study the impact of the surface-energy contribution on the
      inert shock compression of TATB, TNT, alpha-RDX, and beta-HMX nano-grains
      (triaminotrinitrobenzene, trinitrotoluene, hexogen and octogen, respectively). We
      compute the radius-dependent surface energy and combine it with an ab initio
      based equation of state in order to obtain the resulting shock properties through
      the Rankine-Hugoniot relations. We find that the enhancement of the surface
      energy results in a moderate overheating under shock compression. This
      contribution is minor with respect to porosity, when compared to a simple
      macroscopic model. This result motivates further atomistic studies on the impact
      of nanoporosity networks on the shock properties.

PMID- 29352794
TI  - A reversible transition in liquid Bi under pressure.
AB  - The electrical resistance of solid and liquid Bi has been measured at high
      pressures and temperatures using a novel experimental design for high sensitivity
      measurements utilizing a "Paris-Edinburgh" toroid large volume press. An
      anomalous sharp decrease in resistivity with increasing temperature at constant
      pressures was observed in the region beyond melting which implies a possible
      novel transition in the melt. The proposed transition was observed across a range
      of pressures both in heating and cooling cycles of the sample demonstrating its
      reversibility. From the measurements it was possible to determine a "phase-line"
      of this transition on the Bi pressure-temperature phase diagram terminating at
      the melting curve.

PMID- 29352796
TI  - Miscibility at the immiscible liquid/liquid interface: A molecular dynamics study
      of thermodynamics and mechanism.
AB  - Molecular dynamics simulations are used to study the dissolution of water into an
      adjacent, immiscible organic liquid phase. Equilibrium thermodynamic and
      structural properties are calculated during the transfer of water molecule(s)
      across the interface using umbrella sampling. The net free energy of transfer
      agrees reasonably well with experimental solubility values. We find that water
      molecules "prefer" to transfer into the adjacent phase one-at-a-time, without co
      transfer of the hydration shell, as in the case of evaporation. To study the
      dynamics and mechanism of transfer of water to liquid nitrobenzene, we collected
      over 400 independent dissolution events. Analysis of these trajectories suggests
      that the transfer of water is facilitated by interfacial protrusions of the water
      phase into the organic phase, where one water molecule at the tip of the
      protrusion enters the organic phase by the breakup of a single hydrogen bond.

PMID- 29352797
TI  - Physical origins of temperature continuity at an interface between a crystal and
      its melt.
AB  - We justify and discuss the physical origins for the assumption of temperature
      continuity at crystal/melt interfaces by performing atomistic simulations. We
      additionally answer why the crystal/melt interfaces differ from the typical
      solid/liquid interfaces, which usually exhibit dissimilarities and a resulting
      temperature drop. We present results for pure silver modeled using the embedded
      atom method and Lennard-Jones potential function and contrast the results with
      each other. We find that the temperature continuity at an interface between a
      crystal and its melt originates from the perfect vibrational coupling, which is
      caused by the interfacial structural diffusivity. This study provides fundamental
      insights into the heat transfer for cases of extremely large heat flux and
      thermal gradients occurring during rapid melting and solidification. The findings
      additionally determine the role of rough surfaces in manipulating the thermal
      conductance in nanodevices.

PMID- 29352798
TI  - Two-component relativistic coupled-cluster methods using mean-field spin-orbit
      integrals.
AB  - A novel implementation of the two-component spin-orbit (SO) coupled-cluster
      singles and doubles (CCSD) method and the CCSD augmented with the perturbative
      inclusion of triple excitations [CCSD(T)] method using mean-field SO integrals is
      reported. The new formulation of SO-CCSD(T) features an atomic-orbital-based
      algorithm for the particle-particle ladder term in the CCSD equation, which not
      only removes the computational bottleneck associated with the large molecular
      orbital integral file but also accelerates the evaluation of the particle
      particle ladder term by around a factor of 4 by taking advantage of the spin-free
      nature of the instantaneous electron-electron Coulomb interaction. Benchmark
      calculations of the SO splittings for the thallium atom and a set of diatomic 2Pi
      radicals as well as of the bond lengths and harmonic frequencies for a set of
      closed-shell diatomic molecules are presented. The basis-set and core-correlation
      effects in the calculations of these properties have been carefully analyzed.

PMID- 29352799
TI  - An atomistic fingerprint algorithm for learning ab initio molecular force fields.
AB  - Molecular fingerprints, i.e., feature vectors describing atomistic neighborhood
      configurations, is an important abstraction and a key ingredient for data-driven
      modeling of potential energy surface and interatomic force. In this paper, we
      present the density-encoded canonically aligned fingerprint algorithm, which is
      robust and efficient, for fitting per-atom scalar and vector quantities. The
      fingerprint is essentially a continuous density field formed through the
      superimposition of smoothing kernels centered on the atoms. Rotational invariance
      of the fingerprint is achieved by aligning, for each fingerprint instance, the
      neighboring atoms onto a local canonical coordinate frame computed from a kernel
      minisum optimization procedure. We show that this approach is superior over
      principal components analysis-based methods especially when the atomistic
      neighborhood is sparse and/or contains symmetry. We propose that the "distance"
      between the density fields be measured using a volume integral of their pointwise
      difference. This can be efficiently computed using optimal quadrature rules,
      which only require discrete sampling at a small number of grid points. We also
      experiment on the choice of weight functions for constructing the density fields
      and characterize their performance for fitting interatomic potentials. The
      applicability of the fingerprint is demonstrated through a set of benchmark
      problems.

PMID- 29352800
TI  - Efficient reactive Brownian dynamics.
AB  - We develop a Split Reactive Brownian Dynamics (SRBD) algorithm for particle
      simulations of reaction-diffusion systems based on the Doi or volume reactivity
      model, in which pairs of particles react with a specified Poisson rate if they
      are closer than a chosen reactive distance. In our Doi model, we ensure that the
      microscopic reaction rules for various association and dissociation reactions are
      consistent with detailed balance (time reversibility) at thermodynamic
      equilibrium. The SRBD algorithm uses Strang splitting in time to separate
      reaction and diffusion and solves both the diffusion-only and reaction-only
      subproblems exactly, even at high packing densities. To efficiently process
      reactions without uncontrolled approximations, SRBD employs an event-driven
      algorithm that processes reactions in a time-ordered sequence over the duration
      of the time step. A grid of cells with size larger than all of the reactive
      distances is used to schedule and process the reactions, but unlike traditional
      grid-based methods such as reaction-diffusion master equation algorithms, the
      results of SRBD are statistically independent of the size of the grid used to
      accelerate the processing of reactions. We use the SRBD algorithm to compute the
      effective macroscopic reaction rate for both reaction-limited and diffusion
      limited irreversible association in three dimensions and compare to existing
      theoretical predictions at low and moderate densities. We also study long-time
      tails in the time correlation functions for reversible association at
      thermodynamic equilibrium and compare to recent theoretical predictions. Finally,
      we compare different particle and continuum methods on a model exhibiting a
      Turing-like instability and pattern formation. Our studies reinforce the common
      finding that microscopic mechanisms and correlations matter for diffusion-limited
      systems, making continuum and even mesoscopic modeling of such systems difficult
      or impossible. We also find that for models in which particles diffuse off
      lattice, such as the Doi model, reactions lead to a spurious enhancement of the
      effective diffusion coefficients.

PMID- 29352801
TI  - Detection of the etiological agents of hospital-acquired pneumonia - validity and
      comparison of different types of biological sample collection: a prospective,
      observational study in intensive care patients.
AB  - BACKGROUND: There is still a lack of evidence as to which method of biological
      sample collection is optimal for identifying bacterial pathogens causing hospital
      acquired pneumonia (HAP). Much effort has been made to find an easy and valid
      approach to be used in clinical practice. METHODS: The primary endpoint of this
      prospective, observational study was to determine the predictive value of
      oropharyngeal swab (OS) and gastric aspiration (GA) as simple and non-invasive
      methods for diagnosing HAP. Their efficacy was compared to endotracheal
      aspiration (ETA) and protected specimen brushing (PSB), the standard methods
      approved for HAP diagnosis. RESULTS: Initially, 56 patients were enrolled.
      Significant amounts of bacterial pathogens were detected in 48 patients (79
      isolates) in Round A and in 39 patients (45 isolates) in Round B (after 72
      hours). The sensitivity rates were: ETA 98%, PSB 31%, OS 64% and GA 67% in Round
      A and ETA 87%, PSB 32%, OS 74% and GA 42% in Round B. Strains of 12 bacterial
      species were identified in the samples. The three most common etiological agents
      (both rounds together) were Klebsiella pneumoniae (23.7%), Burkholderia
      multivorans (21.1%) and Pseudomonas aeruginosa (15.8%). CONCLUSIONS: Blind ETA is
      an optimum method for obtaining biological samples for identification of
      etiological agents causing HAP in intubated patients. Microbial etiological
      agents were more frequently detected in ETA samples than in those collected by
      PSB. If ETA/PSB results are negative, samples may be collected by OS and/or GA as
      these techniques followed ETA in terms of the frequency of pathogen detection.

PMID- 29352802
TI  - [Human alveolar echinococcosis and an overview of the occurrence of Echinococcus
      multilocularis in animals in the Czech Republic].
AB  - Human alveolar echinococcosis (AE) is caused by larval stages of the tapeworm
      Echinococcus multilocularis. In the Czech Republic, screening tests to detect the
      specific infectious agent have been performed since 1998. The first AE cases were
      diagnosed in 2007, and until 2014, a total of 21 diseases were recorded. In
      accordance with radiological, histological, and/or PCR data, serological
      examinations of 699 individuals helped to reveal 15 additional AE cases in the
      period of 2015-2016. From the cumulative data for 1998-2016, it appears that of
      2,695 patients examined, 36 (18 men and 18 women) were diagnosed with AE. Their
      age at diagnosis ranged from 20 to 82 years and was lower for women (mean 43.7,
      median 39.5) than for men (50.9 and 57.5, respectively), but the difference was
      not statistically significant. In the period of 2007-2016, the mean annual
      incidence rate was 0.034 cases/100 000 population. Our study indicates an ongoing
      increase in AE cases. The disease can be autochthonous in nature, as evidenced
      not only by some case history data but also by the detection of the larval stages
      in wild boar (Sus scrofa). AE risk to humans in the Czech Republic is discussed
      in the context of the known data on the presence of various parasite
      developmental stages in animals.

PMID- 29352803
TI  - [Mycological diagnosis of pulmonary Aspergillus infections with a focus on
      serological methods].
AB  - Aspergillus are ubiquitous fungi that can cause serious illnesses in susceptible
      individuals. The most commonly infected organ is the lungs. The severity of the
      disease depends on the degree of the invasion of the lung tissue by fungi, which
      rises proportionally with the development of immunodeficiency. The only way to
      clearly determine the degree to which the lungs have been invaded is to carry out
      a histological examination of a sample of the infected tissue. Conventional
      mycological methods can detect the presence of the fungus in samples from a
      patient's airways by using microscopy or culture techniques. Furthermore, it is
      possible to determine the presence of the specific Aspergillus antigen,
      galactomannan, and of non-specific beta-D-glucan in the serum or bronchoalveolar
      lavage fluid. The detection of antibodies against Aspergillus is only relevant
      for chronic forms of the disease. This article discusses the benefits of
      different mycological examination methods in the diagnosis of various forms of
      pulmonary aspergillosis.

PMID- 29352804
TI  - [Flow cytometry in microbiology].
AB  - Flow cytometry is a method that allows simultaneous measurement and analysis of
      physical and chemical characteristics of cells or other biological particles
      during their passage through the laser beam. Although this method is mainly used
      in the study of cell differentiation and functional analysis of eukaryotic cells,
      the basic principles of flow cytometry can be applied to microorganisms. Methods
      based on the analysis of a single cell, such as flow cytometry, in combination
      with measurement of cell viability using special fluorescent probes allow a
      deeper insight into the diversity of populations and functioning of microbial
      communities and also facilitate understanding the phy-siological diversity of
      seemingly similar acting populations. When using specific fluorescent dyes for
      the selective labeling of selected species of microorganisms, the method is
      potentially very specific. The aim of this paper is a brief overview of
      applications of flow cytometry, which can be used in microbiology.

PMID- 29352805
TI  - [Crohns disease and ulcerative colitis - current view on genetic determination,
      immunopathogenesis and biologic therapy].
AB  - Crohns disease (CD) and ulcerative colitis (UC) are chronic inflammatory
      disorders of the intestine, also called inflammatory bowel diseases (IBD), which
      are not caused by pathogenic microorganisms but result from non-specific
      inflammatory processes in the bowel. IBD are polygenic diseases, as evidenced by
      the genome-wide association studies (GWAS), which have discovered more than 200
      genes or genetic regions to be associated with IBD. Some of them are specific for
      CD or UC; however, there are 110 overlapping genes. In the pathogenesis of CD,
      activation of adaptive immunity mediated by TH1, TH17, or TH1/TH17 cells is
      induced because of disturbances in the mechanisms of innate immunity and
      autophagocytosis. By comparison, the major events that trigger autoimmune
      processes in UC are an increased translocation of commensal bacteria into the
      submucosa because of loose inter-epithelial connections with subsequent
      activation of ILC2, TH9, TH2, and NKT cells. Knowledge of the pathogenesis of a
      disease enables an effective therapy, which is especially true for biological
      therapy. It is noteworthy that monoclonal antibodies directed against the major
      protagonists underlying both CD and UC have failed. It points to the complexity
      of immunopathologic processes that run in both diseases. One can suppose that a
      blockade of one inflammatory pathway is circumvented by an alternative pathway.
      TNF is the principal pro-inflammatory cytokine that plays a major role in CD and
      UC as well. It was therefore decided to treat IBD patients with anti-TNF
      monoclonal antibodies, infliximab or adalimumab. Approximately one half of the CD
      patients and one third of the UC patients respond to this treatment.

PMID- 29352806
TI  - [The prevalence, incidence, persistence and transmission ways of human
      papillomavirus infection (HPV)].
AB  - Human papillomavirus (HPV) is the most common sexually transmitted infection
      worldwide, which may result in the development of benign or malignant tumours.
      HPV infec-tions cause approximately 5% of all human cancers. Infection at all
      sites is strongly associated with sexual behaviour, but this association does not
      appear to explain substantial differences in the prevalence, incidence,
      persistence, and clearance of HPV infection in the anal, genital, and oral areas.
      Discussed are the similarities and differences among the natural histories of
      infection in different anatomical sites of the human body of both genders.
      Despite the huge advances already achieved, more research is needed to suggest
      effective prevention strategies (including the screening of high-risk groups and
      vaccination) for HPV infection and associated diseases.

PMID- 29352807
TI  - Detection of antigen-specific T cells in patients with neuroborreliosis.
AB  - There is a lack of laboratory tests in clinical practice that can detect the
      activity of borrelial infection. This was the reason for testing an antigen
      specific T-cell detection method in patients with neuroborreliosis: the ELISPOT
      method, which is capable of detecting antigen-specific T lymphocytes in clinical
      conditions. A group of 32 patients (20 diagnosed with neuroborreliosis; NB) was
      examined using this commercial method (LymeSpot intrerferon-gamma Assay Kit(r)).
      Of these 20 NB patients, 10 were found to be positive and 10 negative; four of
      the five persons tested prior to the antibiotic treatment were positive. Eight
      patients served as the control group, giving four positive and four negative
      results. The results achieved so far appear to be unequivocal; still, the test
      could be expected: a) in non-specific clinical symptoms with borderline or
      negative proof of antibodies; b) in eraly stage of the disease; c) in the case of
      seropositivity and unequivocal clinical picture. The basic prerequisite for the
      clinical utilization of the method, however, is that it be thoroughly tested.

PMID- 29352809
TI  - A novel PLEC nonsense homozygous mutation (c.7159G > T; p.Glu2387*) causes
      epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a
      case report.
AB  - BACKGROUND: Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM
      #226670) is an autosomal recessive disease, characterized mainly by skin
      blistering at birth or shortly thereafter, progressive muscle weakness, and
      rarely by alopecia. EBS-MD is caused by mutations in the PLEC gene (OMIM
      *601282), which encodes plectin, a structural protein expressed in several
      tissues, including epithelia and muscle. We describe a patient affected with EBS
      MD and diffuse alopecia in which we identified a novel pathogenic mutation by PCR
      amplification of all coding exons and exon-intron boundaries of PLEC gene,
      followed by bidirectional Sanger sequencing. CASE PRESENTATION: The patient, a 28
      year-old female and only child of consanguineous healthy parents, was born after
      uneventful pregnancy. At 2 days of age, she developed skin and oral mucosal
      blistering, accompanied by voice hoarseness. On physical examination as an adult,
      we observed diffuse non-scarring alopecia on the scalp, onychodystrophy
      (pachyonychia) in all 20 nails, dental decay, mild dysphonia, and severe muscle
      atrophy mainly affecting the extremities. Neurological examination showed
      profoundly diminished reflexes. Mutation analysis revealed the patient to be
      homozygous for the novel PLEC nonsense mutation - c.7159G > T (p.Glu2387*) -
      located in exon 31. Thismutation predicts the lack of expression of the full
      length plectin isoform. CONCLUSION: The present case appears to be the second
      association of EBS-MD with diffuse alopecia, both cases having different
      mutations involving PLEC exon 31. It remains to be elucidated whether diffuse
      alopecia results from PLEC mutations and/or from environmental factors.

PMID- 29352808
TI  - Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional
      connectivity analysis.
AB  - BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome
      associated with deficits in cognitive and emotional processing. This syndrome
      represents one of the highest risk factors for the development of schizophrenia.
      Previous studies of functional connectivity (FC) in 22q11DS report aberrant
      connectivity patterns in large-scale networks that are associated with the
      development of psychotic symptoms. METHODS: In this study, we performed a
      functional connectivity analysis using the CONN toolbox to test for differential
      connectivity patterns between 54 individuals with 22q11DS and 30 healthy
      controls, between the ages of 17-25 years old. We mapped resting-state fMRI data
      onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany
      atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we
      determined total linear temporal associations between each. Within the group with
      22q11DS only, we further tested the association between prodromal symptoms of
      psychosis and FC. RESULTS: We observed that relative to controls, individuals
      with 22q11DS displayed increased FC in lobar networks involving the frontal
      frontal, frontal-parietal, and frontal-occipital ROIs. In contrast, FC between
      ROIs in the parietal-temporal and occipital lobes was reduced in the 22q11DS
      group relative to healthy controls. Moreover, positive psychotic symptoms were
      positively associated with increased functional connections between the left
      precuneus and right superior frontal gyrus, as well as reduced functional
      connectivity between the bilateral pericalcarine. Positive symptoms were
      negatively associated with increased functional connectivity between the right
      pericalcarine and right postcentral gyrus. CONCLUSIONS: Our results suggest that
      functional organization may be altered in 22q11DS, leading to disruption in
      connectivity between frontal and other lobar substructures, and potentially
      increasing risk for prodromal psychosis.

PMID- 29352811
TI  - Single nucleotide polymorphisms in genes encoding penicillin-binding proteins in
      beta-lactamase-negative ampicillin-resistant Haemophilus influenzae in Japan.
AB  - OBJECTIVE: beta-Lactamase-negative ampicillin-resistant Haemophilus influenzae is
      a common opportunistic pathogen of hospital- and community-acquired infections,
      harboring multiple single nucleotide polymorphisms in the ftsI gene, which codes
      for penicillin-binding protein-3. The objectives of this study were to perform
      comprehensive genetic analyses of whole regions of the penicillin-binding
      proteins in H. influenzae and to identify additional single nucleotide
      polymorphisms related to antibiotic resistance, especially to ampicillin and
      other cephalosporins. RESULTS: In this genome analysis of the ftsI gene in 27
      strains of H. influenzae, 10 of 23 (43.5%) specimens of group III genotype beta
      lactamase-negative ampicillin-resistant H. influenzae were paradoxically
      classified as ampicillin-sensitive phenotypes. Unfortunately, we could not
      identify any novel mutations that were significantly associated with ampicillin
      minimum inhibitory concentrations in other regions of the penicillin-binding
      proteins, and we reconfirmed that susceptibility to beta-lactam antibiotics was
      mainly defined by previously reported SNPs in the ftsI gene. We should also
      consider detailed changes in expression that lead to antibiotic resistance in the
      future because the acquisition of resistance to antimicrobials can be predicted
      by the expression levels of a small number of genes.

PMID- 29352810
TI  - Ectopic expression of the apple nucleus-encoded thylakoid protein MdY3IP1
      triggers early-flowering and enhanced salt-tolerance in Arabidopsis thaliana.
AB  - BACKGROUND: The roles in photosystem I (PSI) assembly of the nucleus-encoded
      thylakoid protein Y3IP1 who interacts with the plastid-encoded Ycf3 protein that
      has been well-characterized in plants. However, its function and potential
      mechanisms in other aspects remain poorly understood. RESULTS: We identified the
      apple MdY3IP1 gene, which encodes a protein highly homologous to the Arabidopsis
      Y3IP1 (AtY3IP1). Ectopic expression of MdY3IP1 triggered early-flowering and
      enhanced salt tolerance in Arabidopsis plants. MdY3IP1 controlled floral
      transition by accelerating sugar metabolism process in plant cells, thereby
      influencing the expression of flowering-associated genes. The increase in salt
      stress tolerance in MdY3IP1-expressing plants correlated with reduced reactive
      oxygen species (ROS) accumulation, and an increase in lateral root development by
      regulating both auxin biosynthesis and transport, as followed by enhancement of
      salt tolerance in Arabidopsis. Overall, these findings provide new evidences for
      additional functions of Y3IP1-like proteins and their underlying mechanisms of
      which Y3IP1 confers early-flowering and salt tolerance phenotypes in plants.
      CONCLUSIONS: These observations suggest that plant growth and stress resistance
      can be affected by the regulation of the MdY3IP1 gene. Further molecular and
      genetic approaches will accelerate our knowledge of MdY3IP1 functions in PSI
      complex formation and plants stress resistance, and inform strategies for
      creating transgenic crop varieties with early maturity and high-resistant to
      adverse environmental conditions.

PMID- 29352813
TI  - AGE AT MENARCHE AND SEXUAL DEBUT AMONG YOUNG FILIPINO WOMEN.
AB  - There has been a secular decline in age at menarche since the 19th century. Early
      maturing women are more likely to have their sexual debut at a younger age, which
      in turn gives rise to a host of reproductive health and social problems. This
      study used data from five waves of National Demographic and Health Surveys
      conducted in the Philippines between 1993 and 2013 to examine the trends and
      socioeconomic differentials in age at menarche and sexual debut. The changing
      trend in age at menarche and sexual debut was examined across birth cohorts, and
      logistic regressions were used to identify the determinants of early sexual
      debut. In the Philippines, the mean and median ages at menarche declined from
      13.2 years and 12.6 years, respectively, among young women born in 1973-1977, to
      12.9 years and 12.3 years, respectively, among those born in 1993-1997. The
      proportion who had their sexual debut by age 20 increased from 41.2% for the 1968
      1972 birth cohort to 53.4% for the 1988-1992 birth cohort. Filipino women with
      low education, from poor families and living in rural areas were more likely to
      have earlier sexual debut despite attaining menarche at a later age as compared
      with their higher educated counterparts, and those from wealthier families and
      urban areas. Logistic regression analysis showed that, besides marital status,
      women's education and age at menarche were important determinants of early sexual
      debut. However, ethnicity, place of residence and family wealth had no
      significant effects on age at menarche. An increasing proportion of young women
      were found to be having unprotected sexual debut and at a younger age, with
      health and social ramifications. Hence, apart from increasing the enrolment of
      girls in schools and discouraging teenage marriage, there is a need for social
      and health agencies to implement appropriate adolescent sexual and reproductive
      health programmes such as counselling and educational campaigns, as well as
      support services, to address sexual problems among the youth.

PMID- 29352812
TI  - Usefulness of a visual aid in achieving optimal positioning for spinal
      anesthesia: a randomized trial.
AB  - BACKGROUND: Optimal patient positioning is perceived as an essential factor to
      increase the success of performing neuraxial blockade. The primary objective of
      this study was to evaluate the benefit of using a visual image in addition to
      verbal instructions in order to optimize positioning for spinal block. METHODS:
      This was a prospective randomized controlled trial on 85 adult patients
      undergoing lower limb joint replacements at a tertiary academic hospital. Group
      1(n = 43) randomized to receive standardized verbal instructions; Group 2 (n =
      42) received standardized verbal instructions in conjunction with visual aids to
      achieve positioning for spinal anesthesia. The primary outcome measure was the
      time taken to successful dural puncture. Secondary endpoints were the number of
      skin punctures, number of intervertebral levels attempted, success at the first
      intervertebral space attempted and satisfaction of patients and
      anesthesiologists. RESULTS: The unadjusted geometric mean time taken for the
      procedure using verbal instruction alone was 301 s (95% CI: 236-385) compared to
      183 s (95% CI: 143-235) when both verbal and visual instructions were used. Out
      of the participants in group 2, 90% required <=2 skin punctures and 10% required
      >=3 skin punctures compared to 65% and 35% of the participants in group 1
      respectively (p = 0.001). Group 1 required a second anesthesiologist to
      successfully complete the procedure in 6 patients out of 43 (14%) patients
      whereas the first anesthesiologist was noted to be successful in all the 42 cases
      in group 2 (p = 0.03). There were no significant differences in the satisfaction
      scores of anesthesiologists or patients between the groups. First-pass success
      was strongly associated with patient satisfaction (Odds ratio: 5.2; 95% CI: 1.0
      9.5, p = 0.049). CONCLUSIONS: Use of a visual aid in addition to verbal
      instructions to optimize positioning for a spinal block, significantly reduces
      the time taken for the procedure by an average of 2 min, reduces the number of
      skin punctures and increases the success rate of the first anesthesiologist.
      First pass success was strongly associated with patient satisfaction. TRIAL
      REGISTRATION: This study was retrospectively registered 30 August 2016, with the
      Australian New Zealand Clinical trials registry (ACTRN12616001197426).

PMID- 29352814
TI  - Does adherence to the World Cancer Research Fund/American Institute of Cancer
      Research cancer prevention guidelines reduce risk of colorectal cancer in the UK
      Women's Cohort Study?
AB  - Evidence on adherence to diet-related cancer prevention guidelines and
      associations with colorectal cancer (CRC) risk is limited and conflicting. The
      aim of this cohort analysis is to evaluate associations between adherence to the
      World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) 2007
      recommendations and incident CRC. The UK Women's Cohort Study comprises over 35
      372 women who filled in a FFQ at baseline in 1995. They were followed up for CRC
      incidence for a median of 17.4 years, an individual score linking adherence to
      eight of the WCRF/AICR recommendations was constructed. Cox proportional hazards
      regression provided hazard ratios (HR) and 95 % CI for the estimation of CRC
      risk, adjusting for confounders. Following exclusions, 444 CRC cases were
      identified. In the multivariate-adjusted model, women within the second and third
      (highest) categories of the WRCF/AICR score had HR of 0.79 (95 % CI 0.62, 1.00)
      and 0.73 (95 % CI 0.48, 1.10), respectively, for CRC compared with those in the
      lowest, reference category. The overall linear trend across the categories was
      not significant (P=0.17). No significant associations were observed between the
      WCRF/AICR score and proximal colon, distal colon and rectal cancers separately.
      Of the individual score components, a BMI within the normal weight range was
      borderline significantly protective only for rectal cancer in the fully adjusted
      model. In view of the likely different causes of CRC subtypes, further research
      is needed to identify the optimal dietary patterns associated with reducing colon
      and rectal cancer risk, respectively.

PMID- 29352816
TI  - Under-reporting giardiasis; Time to consider the public health implications -
      ERRATUM.

PMID- 29352817
TI  - THE ASSOCIATION BETWEEN SEXUAL BEHAVIOURS AND INITIATION OF POST-SECONDARY
      EDUCATION IN SOUTH AFRICA.
AB  - Although young people in South Africa are growing up in an era where their
      socioeconomic circumstances are seemingly better than those of their parents'
      generation, they face greater risks in their trajectory to adulthood. This is
      mainly because the environment in which they are making sexual decisions is also
      rapidly evolving. Currently, South Africa has the highest prevalence of HIV and
      AIDS in the world among young people aged 15-24. This study examined the effect
      of sexual behaviours initiated in adolescence on enrolment in post-secondary
      education. The analysis was conducted using data from the longitudinal Cape Area
      Panel Study (CAPS, Waves 1-5) conducted in 2002-2009, which focused on young
      people's sexual behaviours in Cape Town, South Africa. The sample was restricted
      to 3213 individuals who reported sexual debut during adolescence. Using logistic
      regression models fitted separately for males and females, the results revealed
      that several factors acted as either hindrances or protective factors to
      enrolment in post-secondary education. Early sexual debut (by age 17) was
      negatively associated with participation in tertiary education. Other variables
      that had a negative effect included not using contraception at first sex,
      parenthood, engaging in risky behaviours such as illegal substance use, cigarette
      smoking and drinking alcohol and neglect of school homework (doing less than an
      hour a day). Higher levels of parental education (except for paternal education
      in the female model), urban residence and higher aspirations and analogous
      behaviours (studying) acted as protective factors and were positively associated
      with post-secondary education initiation. The paper also points to the
      relationship between early sexual debut and persistent socioeconomic inequality
      and provides empirical evidence for re-thinking policy development and
      implementation around schooling and sex education.

PMID- 29352818
TI  - Validity and reliability of the Palliative Care Transition Measure for Caregivers
      (PCTM-C).
AB  - OBJECTIVE: Patients suffering from advanced disease face different care
      transitions. The transition from acute to palliative care is challenging and may
      lead to the discontinuity of care. Family caregivers become important sources of
      information, as patients begin to experience difficulties in coping with
      emotional transition events. The Care Transition Measure was developed to
      evaluate care transitions as experienced by the elderly. It has never been used
      in palliative care. The aim of this study was to test the validity and
      reliability of a modified version of the Palliative Care Transition Measure,
      specifically the Palliative Care Transition Measure for Caregivers (PCTM-C).
      METHOD: The study included two main phases. Phase I focused on the construction
      of a modified version of the Palliative Care Transition Measure through two focus
      groups and by computing the content validity index. Phase II focused on testing
      the psychometric properties of the PCTM-C on 272 family caregivers through
      confirmatory factor analysis. Result The content validity index for each of the
      items was higher than 0.80, whereas that for the scale was 0.95. The model tested
      with confirmatory factor analysis fitted the data well and confirmed that the
      transition measures referred to communication, integrated care and a trusting
      relationship, and therefore the core dimensions of continuity according to
      existing conceptual models. The internal consistency was high (Cronbach's alpha =
      0.94). Significance of results The PCTM-C proved to be a suitable measure of the
      quality of such transitions. It may be used in clinical practice as a continuity
      quality indicator and has the potential to guide interventions to enhance family
      caregivers' experience of care continuity.

PMID- 29352819
TI  - Dietary fibre intake in relation to the risk of incident chronic kidney disease.
AB  - The purpose of this study was primarily to evaluate the association of total
      fibre intake with the risk of incident chronic kidney disease (CKD). We also
      evaluated the association of dietary fibre from fruits, vegetables, cereals and
      legumes with the incidence of CKD in a population-based prospective study. We
      followed up 1630 participants of the Tehran Lipid and Glucose Study for 6.1
      years, who were initially free of CKD. Baseline diet was assessed by a valid and
      reliable FFQ. Estimated glomerular filtration rate (eGFR) was calculated, using
      the Modification of Diet in Renal Disease Study equation, and CKD was defined as
      eGFR <60 ml/min per 1.73 m2. OR using multivariable logistic regression was
      reported for the association of incident CKD with tertiles of dietary fibre
      intake. After adjustment for age, sex, smoking, total energy intake, physical
      activity, diabetes and using angiotensin-converting-enzyme inhibitor, the OR for
      subjects in the highest compared with the lowest tertile of total fibre intake
      was 0.47 (95 % CI 0.27, 0.86). In addition, for every 5 g/d increase in total
      fibre intake, the risk of incident CKD decreased by 11 %. After adjusting for
      potential confounders, OR for participants in the highest compared with the
      lowest tertile of fibre from vegetables was 0.63 (95 % CI 0.43, 0.93) and from
      legumes it was 0.68 (95 % CI 0.47, 0.98). We observed inverse associations
      between total fibre intake and risk of incident CKD, which demonstrate that high
      fibre intake, mainly from legumes and vegetables, may reduce the occurrence of
      CKD.

PMID- 29352820
TI  - Concordance and predictors of concordance of children's dietary intake as
      reported via ecological momentary assessment and 24 h recall.
AB  - OBJECTIVE: To provide preliminary evidence in support of using ecological
      momentary assessment (EMA), a real-time data capture method involving repeated
      assessments, to measure dietary intake in children by examining the concordance
      of children's dietary reports through EMA and 24 h recall. DESIGN: Children
      completed eight days of EMA surveys, reporting on recent dietary intake of four
      pre-specified food categories ('Fruits or Vegetables', 'Chips or Fries',
      'Pastries or Sweets', 'Soda or Energy Drinks'), and completed two 24 h recalls
      during the same period. Concordance of children's reports of intake during
      matched two-hour time windows from EMA and 24 h dietary recall was assessed using
      cross-tabulation. Multilevel logistic regression examined potential person-level
      (i.e. sex, age, ethnicity and BMI category) predictors of concordance. SETTING:
      Children in Los Angeles County, USA, enrolled in the Mothers' and Their
      Children's Health (MATCH) study. SUBJECTS: One hundred and forty-four 144
      children (53 % female; mean age 9.6 (sd 0.9) years; 34.0 % overweight/obese).
      RESULTS: Two-hour concordance varied by food category, ranging from 64.9 % for
      'Fruits/Vegetables' to 89.9 % for 'Soda/Energy Drinks'. In multilevel models,
      overweight/obese (v. lean) was associated with greater odds (OR; 95 % CI) of
      concordant reporting for 'Soda/Energy Drinks' (2.01; 1.06, 4.04) and
      'Pastries/Sweets' (1.61; 1.03, 2.52). Odds of concordant reporting were higher
      for Hispanic (v. non-Hispanic) children for 'Pastries/Sweets' (1.55; 1.02, 2.36)
      and for girls (v. boys) for 'Fruits/Vegetables' (1.36; 1.01, 1.83). CONCLUSIONS:
      Concordance differed by food category as well as by person-level characteristics.
      Future research should continue to explore use of EMA to facilitate dietary
      assessment in children.

PMID- 29352821
TI  - A brief assessment unravels unmet needs of older people in primary care: a mixed
      methods evaluation of the SPICE tool in Portugal.
AB  - Assessments of need may contribute to identifying health problems associated with
      functional deterioration in older people. A shorter version of the Camberwell
      Assessment of Need for the Elderly was developed for routine use in primary care,
      focusing on five domains: Senses, Physical ability, Incontinence, Cognition, and
      Emotional distress (SPICE). We aimed to explore its usefulness and feasibility in
      primary care. We selected a consecutive sample of 51 community-dwelling older
      adults. The SPICE interview was completed by GPs and patients, with perceptions
      about its use in primary care being explored. Needs were identified in 38
      patients. Unmet needs corresponded to 7% of needs overall. 'Emotional distress'
      was the most frequent unmet need. SPICE helped to identify undisclosed needs, was
      well accepted and its importance in clinical evaluation recognised by GPs and
      patients, despite concerns about time constraints. Facilitating strategies are
      needed to improve the feasibility of these assessments in primary care.

PMID- 29352822
TI  - Lower Respiratory Symptoms Associated With Environmental and Reconstruction
      Exposures After Hurricane Sandy.
AB  - OBJECTIVE: In a population with prior exposure to the World Trade Center (WTC)
      disaster, this study sought to determine the relationship between Hurricane Sandy
      related inhalation exposures and post-Sandy lower respiratory symptoms (LRS).
      METHODS: Participants included 3835 WTC Health Registry enrollees who completed
      Wave 3 (2011-2012) and Hurricane Sandy (2013) surveys. The Sandy-related
      inhalational exposures examined were: (1) reconstruction exposure; (2) mold or
      damp environment exposure; and (3) other respiratory irritants exposure. LRS were
      defined as wheezing, persistent cough, or shortness of breath reported on >=1 of
      the 30 days preceding survey completion. Associations between LRS and Sandy
      exposures, controlling for socio-demographic factors, post-traumatic stress
      disorder, and previously reported LRS and asthma were examined using multiple
      logistic regression. RESULTS: Over one-third of participants (34.4%) reported
      post-Sandy LRS. Each of the individual exposures was also independently
      associated with post-Sandy LRS, each having approximately twice the odds of
      having post-Sandy LRS. We found a dose-response relationship between the number
      of types of Sandy-related exposures reported and post-Sandy LRS. CONCLUSIONS:
      This study provides evidence that post-hurricane clean-up and reconstruction
      exposures can increase the risk for LRS. Public health interventions should
      emphasize the importance of safe remediation practices and recommend use of
      personal protective equipment. (Disaster Med Public Health Preparedness.
      2018;page 1 of 6).

PMID- 29352823
TI  - Neurocognitive and Self-efficacy Benefits of Cognitive Remediation in
      Schizophrenia: A Randomized Controlled Trial.
AB  - OBJECTIVES: The aim of this study was to evaluate the impact of computer-assisted
      "drill-and-strategy" cognitive remediation (CR) for community-dwelling
      individuals with schizophrenia on cognition, everyday self-efficacy, and
      independent living skills. METHODS: Fifty-six people with schizophrenia or
      schizoaffective disorder were randomized into CR or computer game (CG) playing
      (control), and offered twenty 1-hr individual sessions in a group setting over 10
      weeks. Measures of cognition, psychopathology, self-efficacy, quality of life,
      and independent living skills were conducted at baseline, end-group and 3 months
      following intervention completion. RESULTS: Forty-three participants completed at
      least 10 sessions and the end-group assessment. Linear mixed-effect analyses
      among completers demonstrated a significant interaction effect for global
      cognition favoring CR (p=.028). CR-related cognitive improvement was sustained at
      3-months follow-up. At end-group, 17 (77%) CR completers showed a reliable
      improvement in at least one cognitive domain. A significant time effect was
      evident for self-efficacy (p=.028) with both groups improving over time, but no
      significant interaction effect was observed. No significant effects were found
      for other study outcomes, including the functional measure. CONCLUSIONS: Computer
      assisted drill-and-strategy CR in schizophrenia improved cognitive test
      performance, while participation in both CR and CG playing promoted enhancements
      in everyday self-efficacy. Changes in independent living skills did not appear to
      result from CR, however. Adjunctive psychosocial rehabilitation is likely
      necessary for improvements in real-world community functioning to be achieved.
      (JINS, 2018, 24, 549-562).

PMID- 29352824
TI  - Evaluating the Effect of a Clostridium difficile Infection Prevention Initiative
      in Veterans Health Administration Long-Term Care Facilities.
AB  - We evaluated rates of clinically confirmed long-term-care facility-onset
      Clostridium difficile infections from April 2014 through December 2016 in 132
      Veterans Affairs facilities after the implementation of a prevention initiative.
      The quarterly pooled rate decreased 36.1% from the baseline (P<.0009 for trend)
      by the end of the analysis period. Infect Control Hosp Epidemiol 2018;39:343-345.

PMID- 29352825
TI  - Safety of Electro-Medical Equipment in Floods in Austere Environment.
AB  - Pakistan is prone to floods. In 2010, floods in North-Western Pakistan caused
      devastation in wide areas. Electro-medical equipment is very expensive and
      without proper equipment adequate surgery is not possible. We retrospectively
      analyzed how expensive electro-medical equipment got damaged during floods of
      2010 at a district-level hospital in North-Western Pakistan and how we could have
      saved this equipment or reduced the damage to the minimum. The article provides
      the lessons learned and recommendations aimed to prevent or minimize damage to
      the valuable and expensive equipment in the areas prone to floods. (Disaster Med
      Public Health Preparedness. 2018;page 1 of 3).

PMID- 29352826
TI  - The in vitro antileishmanial activity of essential oil from Aloysia gratissima
      and guaiol, its major sesquiterpene against Leishmania amazonensis.
AB  - Leishmaniases is a tropical disease caused by protozoa of the genus Leishmania
      for which the current treatment is expensive, besides increasing reports of
      parasite resistance. This study investigated the anti-Leishmania amazonensis
      activity of the essential oil from Aloysia gratissima (AgEO) and guaiol, the
      major sesquiterpene constituent in the oil. Our results showed that AgEO killed
      promastigotes and intracellular amastigotes at an IC50 of 25 and 0.16 ug mL-1,
      respectively, while guaiol killed amastigotes at an IC50 of 0.01 ug mL-1. Both
      AgEO and guaiol were safe for macrophages up to 100 ug mL-1, as evaluated by the
      dehydrogenase activity, membrane integrity and phagocytic capacity. AgEO and
      guaiol did not induce nitrite oxide (NO) in resting macrophages and inhibited the
      production of NO in lipopolysaccharide-stimulated macrophages. The
      ultrastructural analysis suggested that AgEO and guaiol act directly on
      parasites, affecting promastigotes kinetoplast, mitochondrial matrix and plasma
      membrane. Together, these results pointed out that AgEO and guaiol could be
      promising candidates to develop anti-Leishmania drugs.

PMID- 29352827
TI  - Political terrorism and affective polarization in "black" and "red" terrorists in
      Italy during the years 1968-1988.
AB  - Psychiatric evaluations of violent political crime were mostly performed on a
      case-by-case basis in a forensic environment, which made them unduly dependent on
      categories of presumed dangerousness and legal responsibility, rather than on a
      clinical definition of their mental status. In referring to such "clinical"
      definitions, the disorder we have in mind is not limited to the major, agitated
      psychotic manias or mixed states. The presence of a dominant temperament, or
      protracted hypomania, is enough by itself to explain an individual's engagement
      in a wide range of activities, not necessarily sociopathic or violent. We put
      forward the hypothesis that formal and transpolitical radical choices, either in
      favor of an illegal lifestyle or of activities involving a high level of risk,
      may be linked with certain mental states, especially when considering small
      clandestine groups showing a high level of internal ideological consensus, and a
      no-return attitude toward a commitment to radical choices. Available data about
      the psycho(patho)logical profile of terrorists are still hard to come by. The
      only available studies are those on identified living terrorists (judging by the
      trials of those who personally admitted to having been terrorists), and
      statistical data imply a number of documented cases belonging to the same
      terrorist organization. In Italy, the period often called the "years of lead
      [bullets]" displays an interesting viewpoint for the study of terrorist
      psychology, for two main reasons: first of all, it is a historically defined
      period (1968-1988), and second, the number of ascertained participants in
      terrorist activities was quite large.

PMID- 29352828
TI  - Sensitivity of fatty acid desaturation and elongation to plasma zinc
      concentration: a randomised controlled trial in Beninese children.
AB  - Zn status may affect fatty acid (FA) metabolism because it acts as a cofactor in
      FA desaturase and elongase enzymes. Zn supplementation affects the FA desaturases
      of Zn-deficient rats, but whether this occurs in humans is unclear. We evaluated
      the associations between baseline plasma Zn (PZn) concentration and plasma total
      phospholipid FA composition, as well as the effect of daily consumption of Zn
      fortified water on FA status in Beninese children. A 20-week, double-blind
      randomised controlled trial was conducted in 186 school age children. The
      children were randomly assigned to receive a daily portion of Zn-fortified,
      filtered water delivering on average 2.8 mg Zn/d or non-fortified filtered water.
      Plasma total phospholipid FA composition was determined using capillary GLC and
      PZn concentrations by atomic absorption spectrometry. At baseline, PZn correlated
      positively with dihomo-gamma-linolenic acid (DGLA, r 0.182; P=0.024) and the
      DGLA:linoleic acid (LA) ratio (r 0.293; P<0.000), and negatively with LA (r 
      0.211; P=0.009) and the arachidonic acid:DGLA ratio (r -0.170; P=0.036). With the
      intervention, Zn fortification increased nervonic acid (B: 0.109; 95 % CI 0.001,
      0.218) in all children (n 186) and more so in children who were Zn-deficient (n
      60) at baseline (B: 0.230; 95 % CI 0.023, 0.488). In conclusion, in this study,
      Zn-fortified filtered water prevented the reduction of nervonic acid composition
      in the plasma total phospholipids of children, and this effect was stronger in Zn
      deficient children. Thus, Zn status may play an important role in FA desaturation
      and/or elongation.

PMID- 29352829
TI  - The WHO recommendation of home fortification of foods with multiple-micronutrient
      powders in children under 2 years of age and its effectiveness on anaemia and
      weight: a pragmatic cluster-randomized controlled trial.
AB  - OBJECTIVE: To assess under real community settings the effectiveness of the WHO
      strategy of home fortification of foods (HFF) with multiple-micronutrient powders
      on Hb change, anaemia and weight in children. DESIGN: A pragmatic cluster
      randomized controlled trial. SETTING: Forty villages in the Nioro Circle in Mali
      and 722 children aged 6-23 months were randomized to the intervention or control
      group. The intervention consisted of a daily dose of multiple-micronutrient
      powder for 3 months; in the control group, no supplement was given. In both
      groups, mothers received group education on child complementary feeding. Changes
      in weight, Hb concentration and anaemia were assessed as primary outcomes at
      baseline and 3 months. The HFF effect was determined using regression analyses
      and quantile regression with standard errors taking account of the cluster
      design. SUBJECTS: Children aged 6-23 months. RESULTS: Overall prevalence of
      anaemia in the sample was high: 90 %. HFF provided a modest but statistically
      significant Hb change v. no intervention (0.50 v. 0.09 g/dl, P=0.023). Prevalence
      of anaemia changed little: 91.3-85.8 % (P=0.04) in the intervention group v. 88.1
      87.5 % % (P=0.86) in the control group. Proportion of severe anaemia was reduced
      by 84 % (from 9.8 to 1.6 %) in the intervention group, but increased in the
      control group (from 8.5 to 10.8 %). No effect was observed on weight.
      CONCLUSIONS: The WHO HFF strategy to fight anaemia showed a modest change on Hb
      concentration and significantly reduced the rate of severe anaemia.

PMID- 29352830
TI  - Schistosoma mansoni and endocarditis: from egg to free DNA detection in Egyptian
      patients and infected BALB/c mice.
AB  - With the growing incidence of closed schistosomiasis and uncommon presentations,
      there is a risk of the infection rate being underestimated. A study in Japan
      reported an unexplained case of endocarditis that was finally diagnosed as a
      complex Schistosoma japonicum infection; in the absence of advanced techniques,
      the diagnosis was delayed. We therefore set out to explore the incidence of
      Schistosoma mansoni in endocarditis patients coming from areas of Egypt where S.
      mansoni is endemic. We also investigated histopathological changes in the cardiac
      valves and the presence of cell-free parasite DNA (CFPD) in cardiac tissues of
      laboratory mice infected with S. mansoni. The study included 186 patients with
      the manifestations of infective endocarditis. Eggs were detected in the stool
      samples of 5.91% of patients. Seropositivity was reported in 23.66% of patients
      and antigen was detected in the urine samples of 10.21%. Using real-time
      polymerase chain reaction (PCR), CFPD was detected in the blood of 6.98% of the
      endocarditis patients and 95% of the infected mice, while the cardiac samples of
      45% of the mice tested positive for CFPD (means +/- SD = 1390.2 +/- 283.65,
      2158.72 +/- 1103.1 and 5.71 +/- 2.91, respectively). Histopathological
      examination revealed abnormal collagen deposition, inflammatory cells and
      haemorrhagic pigmentation in the heart sections. Despite the low incidence of S.
      mansoni infection in the studied cohort, the presence of CFPD in the cardiac
      tissue of infected mice makes it necessary to: (1) investigate the hazards of
      CFPD deposition in endothelium-rich organs; and (2) test the potential of CFPD to
      trigger tissue inflammation, abnormal proliferation or genome integration.

PMID- 29352831
TI  - Associations between adherence to the Danish Food-Based Dietary Guidelines and
      cardiometabolic risk factors in a Danish adult population: the DIPI study.
AB  - Diet is recognised as one modifiable lifestyle factor for ischaemic heart disease
      (IHD). We aimed at investigating the associations between adherence to the Danish
      Food-Based Dietary Guidelines (FBDG) indicated by a Dietary Quality Index (DQI)
      and selected cardiometabolic risk factors in a cross-sectional study with 219
      Danish adult participants (59 %women; age 31-65years) with a minimum of one self
      rated risk marker of IHD. Information regarding diet was obtained using web-based
      dietary assessment software and adherence to the Danish FBDG was expressed by a
      DQI calculated from 5 food and nutrient indicators (whole grain, fish, fruit and
      vegetables, energy from saturated fat and from added sugar). Background
      information, blood samples and anthropometrics were collected and blood pressure
      was measured. Linear regression analyses were used to evaluate the association
      between DQI and cardiometabolic risk factors. DQI was inversely associated with
      LDL:HDL ratio and TAG (-0.089 per unit; 95 % CI -0.177, -0.002 and -5 % per unit;
      95 % CI -9, 0, respectively) and positively associated with HDL-cholesterol
      (0.047 mmol/l per unit; 95 % CI 0.007, 0.088). For men, DQI was inversely
      associated with BMI (-3 %per unit; 95 % CI -5, -1), trunk fat (-1 % per unit; 95
      % CI -2, -1), high-sensitivity C-reactive protein (-30 % per unit; 95 % CI -41, 
      16 %), HbA1c (-0.09 % per unit; 95 % CI -0.14, -0.04), insulin (-13 % per unit;
      95 % CI -19, -7) and homoeostatic model assessment-insulin resistance (-14 % per
      unit; 95 % CI -21, -7). In women, DQI was positively associated with systolic
      blood pressure (2.6 mmHg per unit; 95 % CI 0.6, 4.6). In conclusion, higher
      adherence to the current Danish FBDG was associated with a more beneficial
      cardiometabolic risk profile in a Danish adult population with a minimum of one
      self-rated risk factor for IHD.

PMID- 29352832
TI  - "You either need help...you feel you don't need help...or you don't feel worthy
      of asking for it:" Receptivity to bereavement support.
AB  - OBJECTIVE: Although the needs of the bereaved have been identified widely in the
      literature, how these needs translate into meaningful, appropriate, and client
      centered programs needs further exploration. The application of receptivity to
      support is a critical factor in participation by the bereaved in palliative care
      bereavement programs. Receptivity is a complex multifactorial phenomenon
      influenced by internal and external factors that ultimately influences engagement
      in psychosocial support in bereavement. This study explored factors that
      influence receptivity to bereavement support from palliative care services in
      rural, regional, and remote Western Australia. METHOD: The study comprised a
      qualitative descriptive research design using semistructured interviews with 24
      bereaved individuals, nine palliative care health professionals, and four
      Aboriginal Health Professionals. Participants were recruited via palliative care
      services in country Western Australia. Interviews were transcribed verbatim and
      thematically analyzed. Result Findings revealed that a range of individual,
      social, and geographical factors influence receptivity to bereavement support and
      can impact on utilization of bereavement support services. Significance of
      results Receptivity provides a frame of reference to enhance understanding of
      factors influencing engagement in psychosocial support in bereavement.
      Receptivity promotes a shift of service provider perspectives of effective
      supportive care to consumer-centric reasons for engagement.

PMID- 29352833
TI  - Consuming sustainable seafood: guidelines, recommendations and realities.
AB  - OBJECTIVE: Encouraging people to eat more seafood can offer a direct, cost
      effective way of improving overall health outcomes. However, dietary
      recommendations to increase seafood consumption have been criticised following
      concern over the capacity of the seafood industry to meet increased demand, while
      maintaining sustainable fish stocks. The current research sought to investigate
      Australian accredited practising dietitians' (APD) and public health
      nutritionists' (PHN) views on seafood sustainability and their dietary
      recommendations, to identify ways to better align nutrition and sustainability
      goals. DESIGN: A self-administered online questionnaire exploring seafood
      consumption advice, perceptions of seafood sustainability and information sources
      of APD and PHN. Qualitative and quantitative data were collected via open and
      closed questions. Quantitative data were analysed with chi 2 tests and reported
      using descriptive statistics. Content analysis was used for qualitative data.
      SETTING: Australia. SUBJECTS: APD and PHN were targeted to participate; the
      sample includes respondents from urban and regional areas throughout Australia.
      RESULTS: Results indicate confusion around the concept of seafood sustainability
      and where to obtain information, which may limit health professionals' ability to
      recommend the best types of seafood to maximise health and sustainability
      outcomes. Respondents demonstrated limited understanding of seafood
      sustainability, with 7.5 % (n 6/80) satisfied with their level of understanding.
      CONCLUSIONS: Nutrition and sustainability goals can be better aligned by
      increasing awareness on seafood that is healthy and sustainable. For health
      professionals to confidently make recommendations, or identify trade-offs, more
      evidence-based information needs to be made accessible through forums such as
      dietetic organisations, industry groups and nutrition programmes.

PMID- 29352834
TI  - Confidence in communicating with patients with cancer mediates the relationship
      between rehabilitation therapists' autistic-like traits and perceived difficulty
      in communication.
AB  - OBJECTIVE: Recently, rehabilitation therapists have become involved in cancer
      rehabilitation; however, no communication skills training that increases the
      ability to provide emotional support for cancer patients has been developed for
      rehabilitation therapists. In addition, no study has examined associations
      between rehabilitation therapists' communication skills and their level of
      autistic-like traits (ALT), which are in-born characteristics including specific
      communication styles and difficulty communicating with patients. In this study,
      we aimed to investigate whether confidence in communicating with patients
      mitigates communication difficulties experienced by rehabilitation therapists who
      have high levels of ALT. METHOD: Rehabilitation therapists who treat patients
      with cancer completed self-administered postal questionnaires anonymously. Scores
      were obtained on the Autism-Spectrum Quotient short form, confidence in
      communication, and communication difficulties. We used covariance structure
      analyses to test hypothetical models, and confirmed that confidence in
      communication mediates the relationship between ALT and perceived communication
      difficulties. RESULTS: Participants included 1,343 respondents (49.6%). Autism
      Spectrum Quotient scores were positively correlated with communication
      difficulties (r = 0.16, p < 0.001). The correlation was mitigated by confidence
      in communication in the fit model. However, higher confidence in creating a
      supportive atmosphere was associated with more difficulty in communication (r =
      0.16, p < 0.001). Significance of results Communication difficulty was linked to
      rehabilitation therapists' ALTs. By increasing confidence in areas of
      communication other than creation of a supportive atmosphere, ALT-related
      difficulties in communication may be ameliorated. Confidence to create supportive
      environments correlated positively with difficulty. Communication skills training
      to increase confidence in communication for rehabilitation therapists should be
      developed with vigilance regarding ALT levels.

PMID- 29352835
TI  - A Gap Analysis Survey of US Aircraft Rescue and Fire Fighting (ARFF) Members to
      Determine Highly Infectious Disease Training and Education Needs.
AB  - OBJECTIVE: Despite lessons learned from the recent Ebola epidemic, attempts to
      survey and determine non-health care worker, industry-specific needs to address
      highly infectious diseases have been minimal. The aircraft rescue and fire
      fighting (ARFF) industry is often overlooked in highly infectious disease
      training and education, even though it is critical to their field due to elevated
      occupational exposure risk during their operations. METHODS: A 44-question gap
      analysis survey was distributed to the ARFF Working Group to determine where
      highly infectious education and training can be improved. In total, N=245
      responses were initiated and collected. Descriptive statistics were generated
      utilizing Qualtrics Software Version 2016.17(c). RESULTS: Supervisors perceived
      Frontline respondents to be more willing and comfortable to encounter potential
      highly infectious disease scenarios than the Frontline indicated. More than one
      third of respondents incorrectly marked transmission routes of viral hemorrhagic
      fevers. There were discrepancies in self-reports on the existence of highly
      infectious disease orientation and skills demonstration, employee resources, and
      personal protective equipment policies, with a range of 7.5%-24.0% more
      Supervisors than Frontline respondents marking activities as conducted.
      CONCLUSIONS: There are deficits in highly infectious disease knowledge, skills,
      and abilities among ARFF members that must be addressed to enhance member safety,
      health, and well-being. (Disaster Med Public Health Preparedness. 2018;page 1 of
      5).

PMID- 29352836
TI  - Implementation of the integrated palliative care outcome scale in acute care
      settings - a feasibility study.
AB  - OBJECTIVE: Although hospitals have been described as inadequate place for end-of
      life care, many deaths still occur in hospital settings. Although patient
      reported outcome measures have shown positive effects for patients in need of
      palliative care, little is known about how to implement them. We aimed to explore
      the feasibility of a pilot version of an implementation strategy for the
      Integrated Palliative care Outcome Scale (IPOS) in acute care settings. METHOD: A
      strategy, including information, training, and facilitation to support the use of
      IPOS, was developed and carried out at three acute care units. For an even
      broader understanding of the strategy, it was also tested at a palliative care
      unit. A process evaluation was conducted including collecting quantitative data
      and performing interviews with healthcare professionals. Result Factors related
      to the design and performance of the strategy and the context contributed to the
      results. The prevalence of completed IPOS in the patient's records varied from 6%
      to 44% in the acute care settings. At the palliative care unit, the prevalence in
      the inpatient unit was 53% and the specialized home care team 35%. The
      qualitative results showed opposing perspectives concerning the training
      provided: Related to everyday work at the acute care units and Nothing in it for
      us at the palliative care unit. In the acute care settings, A need for an
      improved culture regarding palliative care was identified. A context
      characterized by A constantly increasing workload, a feeling of Constantly on
      going changes, and a feeling of Change fatigue were found at all units.
      Furthermore, the internal facilitators and the nurse managers' involvement in the
      implementation differed between the units. Significance of the results The
      feasibility of the strategy in our study is considered to be questionable and the
      components need to be further explored to enhance the impact of the strategy and
      thereby improve the use of IPOS.

PMID- 29352837
TI  - Socio-economic determinants of vitamin D deficiency in the older Polish
      population: results from the PolSenior study.
AB  - OBJECTIVE: Numerous studies have reported an association between vitamin D (25
      hydroxyvitamin D; 25(OH)D) deficiency and low economic status, lower educational
      level, drugs exposure, smoking and reduced physical activity. Our study analysed
      the association between sociodemographic factors and 25(OH)D status in Polish
      (Caucasian) seniors. DESIGN: Cross-sectional study (part of the PolSenior study).
      Serum 25(OH)D concentration was measured by a solid-phase ELISA method; a
      standardized questionnaire evaluated educational level, economic status, alcohol
      consumption, current or past cigarette smoking, physical activity, activities of
      daily living (ADL) and instrumental activities of daily living. SETTING:
      Community-dwelling randomly selected individuals aged 65 years or older, selected
      using three-stage stratified, proportional draw. SUBJECTS: Seniors (n 3472; 1658
      women and 1814 men). RESULTS: Mean serum 25(OH)D concentration was 20.5 (sd 9.6)
      ng/ml. Values below the recommended level (30 ng/ml) were detected in 82.8 % of
      men and 90.4 % of women. Regression analysis revealed that the difference between
      sexes was associated with decreased walking activity in women, probably resulting
      in less sunlight exposure. There was a positive association between any
      disability in ADL and the presence of vitamin D deficiency/insufficiency. In the
      sex-adjusted analysis, older age, alcohol abstinence and lack of cycling and long
      distance walking were explanatory variables for vitamin D deficiency.
      CONCLUSIONS: Vitamin D deficiency/insufficiency is frequent in the older Polish
      population and associated with functional disability and impaired mobility of
      seniors.

PMID- 29352838
TI  - Reduction or cessation of antiviral agents in hepatitis B virus carriers treated
      with biologic agents.

PMID- 29352839
TI  - The new frontier of imaging: the micron.

PMID- 29352840
TI  - Serum aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1), a
      novel disease activity predictive biomarker of systemic lupus erythematosus.
AB  - OBJECTIVES: Secreted aminoacyl-tRNA synthetase-interacting multifunctional
      protein-1 (AIMP1) has been reported to have pro-inflammatory properties. The aim
      of this study was to evaluate the clinical significance of serum AIMP1 in
      patients with systemic lupus erythematosus (SLE). METHODS: Serum levels of AIMP1
      were measured in 160 patients with SLE using a human AIMP1 ELISA kit. Eighty
      patients were classified as active SLE (SLEDAI-2K >= 5), and 80 patients were
      classified as stable SLE. Correlation between serum AIMP1, SLE disease activity
      index-2000 (SLEDAI-2K), and laboratory variables related to disease activity or
      inflammatory burdens were assessed using Pearson's correlation analysis. The
      optimal cut-off value for serum AIMP1 to predict active SLE was estimated by
      using a receiver operator characteristic curve, and logistic regression analysis
      was used to compare the odds ratios (ORs) of laboratory variables in predicting
      active SLE. RESULTS: The median serum AIMP1 was higher in patients with active
      SLE than those with stable SLE (8.0 vs. 6.5 ng/ml, p<0.001). Serum AIMP1
      demonstrated correlation with SLEDAI-2K and laboratory variables related to
      disease activity or inflammatory burdens. The optimal cut-off AIMP1 to predict
      active SLE was 10.09. Multivariate logistic regression analysis including
      conventional laboratory variables demonstrated that serum AIMP1 >=10.09 ng/ml (OR
      3.919, 95% confidence interval 1.223-12.564, p=0.022) was useful in predicting
      active SLE. CONCLUSIONS: Serum levels of AIMP1 were associated with disease
      activity of SLE and could predict active SLE based on SLEDAI-2K.

PMID- 29352841
TI  - Predict rheumatoid arthritis conversion from undifferentiated arthritis with
      dynamic contrast-enhanced MRI and laboratory indexes.
AB  - OBJECTIVES: To investigate the clinical value of dynamic contrast-enhanced MRI
      (DCE-MRI) and laboratory indexes in predicting conversion from undifferentiated
      arthritis (UA) to rheumatoid arthritis (RA). METHODS: A total 81 DMARD-naive UA
      patients were studied. 37 cases were ultimately diagnosed as RA, 32 cases were
      diagnosed as other types of arthritis, and the remaining cases were still UA
      during the 1-year follow-up. The DCE-MRI and laboratory measures were fed into a
      logistic regression analysis. RESULTS: Wash-in rate and anti-cyclic citrullinated
      peptide (anti-CCP) antibody served as the final variables into the regression
      equation (p<0.05). The area under the ROC curve of wash-in rate was 0.966. With
      optimal cut-off point 29.84 s-1, wash-in rate achieved a sensitivity of 94.6% and
      specificity of 88.6% for predicting RA conversion from UA; anti-CCP antibody
      positive achieved a sensitivity of 37.8% and specificity of 90.9%. The
      combination of wash-in rate and anti-CCP antibody positive improved specificity
      (100%) but not sensitivity (27.3%). CONCLUSIONS: The conversion from UA to RA is
      highly predictable. The wash-in rate of DCE-MRI can be used as an important
      biomarker to predict UA progression.

PMID- 29352842
TI  - Amylin in the insulin resistance of patients with rheumatoid arthritis.
AB  - OBJECTIVES: Amylin, which is co-secreted with insulin, plays a role in glycemic
      regulation and is impaired in type 2 diabetes. In the present study we assess,
      for the first time, the implication of amylin in the development of insulin
      resistance (IR) in rheumatoid arthritis (RA). METHODS: This was a cross-sectional
      study involving 361 non-diabetic individuals, 151 patients with RA and 210 sex
      matched controls. Insulin, C-peptide, amylin, lipoprotein serum concentrations,
      and IR indexes by homeostatic model assessment (HOMA2) were evaluated in patients
      and controls. A multivariable analysis, adjusted for IR-related factors, was
      performed to determine the differences between patients and controls vis-a-vis
      amylin and how it is related to IR in RA. RESULTS: Insulin, C-peptide and HOMA2
      IR indexes were higher in RA patients than in controls. Amylin serum levels were
      found to be upregulated in RA patients compared to controls (1.36 +/- 0.81 vs.
      1.79 +/- 1.51 ng/ml, p=0.011), although this difference was lost after adjusting
      for covariates (p=0.46). While amylin positively correlated with the presence of
      rheumatoid factor (beta coef. 0.90 [95%CI -0.23-1.56], p=0.009) and SDAI (beta
      coef 0.01 [95%CI 0.00-0.03], p=0.034), no significant association with other
      disease activity scores, glucocorticoid intake, methotrexate use or TNF-alpha
      inhibitors was found. CONCLUSIONS: IR in RA does not appear to be mediated by
      amylin. This would imply that the mechanisms associated with IR in RA patients
      differ from those at work in type 2 diabetes.

PMID- 29352843
TI  - Tocilizumab after a first-line with anti-TNF in rheumatoid arthritis: a cost
      consequence analysis in the Italian setting.
AB  - OBJECTIVES: Switching to a different mechanism of action in rheumatoid arthritis
      (RA) patients after a first anti-TNF-alpha has proved to be effective. The
      objective of this study was a health economic assessment in Italy. METHODS: The
      study was conducted using a pharmacoeconomic model with a 3-year time horizon.
      Effectiveness was measured as days gained in low disease activity (LDA; DAS28-ESR
      <3.2) or in remission (DAS28-ESR <2.6). The model simulated the response to
      treatments, based on the Rotation Or Change (ROC) trial, the probability of
      discontinuation and switch to a 3rd-line biologic, and the transition to death.
      Time on treatment curves for 2nd-line biologics were derived from published
      Italian real-word data. Costs were estimated based on published sources and
      Italian prices and tariffs. RESULTS: The switch to tocilizumab after the failure
      of a first anti-TNF-alpha was more effective than a second anti-TNF-alpha, in
      terms of days in remission (224 vs. 114 days) and of days in LDA (345 vs. 193
      days). The cost-consequence ratio with tocilizumab iv was 174 euros/day in
      remission and 113 euros/day in LDA. With tocilizumab sc the ratio was 181
      euros/day in remission and 117 euros/day in LDA. The same ratios for the anti-TNF
      alpha treatments ranged from 233 to Euro 320 euros per day in remission and from
      138 to 190 euros per day in LDA. CONCLUSIONS: The switch to a different mechanism
      of action, namely tocilizumab, after the failure of a first anti-TNF-alpha agent
      seems a rational strategy for RA patients in the Italian setting.

PMID- 29352844
TI  - Hypoalbuminaemia in antineutrophil cytoplasmic antibody-associated vasculitis:
      incidence and significance.
AB  - OBJECTIVES: Hypoalbuminaemia has been proved to be a biomarker of poor prognosis
      in many diseases. The objective of this study was to investigate the significance
      of hypoalbuminaemia in antineutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV). METHODS: Data of 117 AAV patients were analysed
      retrospectively. The relationship between hypoalbuminaemia and disease severity
      were studied. The influence of albumin on the pathogenetic role of ANCA was
      investigated in vitro. RESULTS: Among all patients, 52 had light hypoalbuminaemia
      (30g/L<=albumin<35g/L) and 40 had nephrotic hypoalbuminaemia (albumin <30g/L).
      Patients with hypoalbuminaemia had higher inflammation levels and more severe
      kidney injury than patients without hypoalbuminaemia, but no significant
      difference of the urinary protein levels were found between patients with
      nephrotic and light hypoalbuminaemia. Multivariate analysis showed serum albumin
      correlated with age (r=-0.566, p=0.018), C-reactive protein (r=-0.521, p=0.032)
      and haemoglobin (r=0.512, p=0.036). Patients with nephrotic hypoalbuminaemia had
      higher incidence of infection, end stage renal disease and all cause mortality
      during treatment than patients with light hypoalbuminaemia or normal serum
      albumin. In vitro study indicated albumin could inhibit the binding between ANCA
      and neutrophils in a concentration dependent manner. Albumin also inhibited the
      ANCA-induced respiratory burst and neutrophil extracellular traps formation.
      CONCLUSIONS: Serum albumin have an inhibitory effect on the binding between ANCA
      and its antigen. The incidence of hypoalbuminaemia in AAV with kidney involvement
      is high but is not caused by heavy proteinuria. Hypoalbuminaemia is correlated
      with the high inflammation level and poor prognosis of AAV. Therapy targeting
      hypoalbuminaemia might benefit patients with AAV.

PMID- 29352845
TI  - Rapidly progressive glomerulonephritis caused by overlap syndrome of IgG4-related
      tubulointerstitial nephritis and myeloperoxidase-antineutrophil cytoplasmic
      antibody-associated necrotising glomerulonephritis.

PMID- 29352846
TI  - The Janus kinase inhibitor tofacitinib inhibits TNF-alpha-induced gliostatin
      expression in rheumatoid fibroblast-like synoviocytes.
AB  - OBJECTIVES: Gliostatin (GLS) is known to have angiogenic and arthritogenic
      activity, and GLS expression levels in serum from patients with rheumatoid
      arthritis (RA) are significantly correlated with the disease activity.
      Tofacitinib is a novel oral Janus kinase (JAK) inhibitor and is effective in
      treating RA. However, the mechanism of action of tofacitinib in fibroblast-like
      synoviocytes (FLSs) has not been elucidated. The purpose of this study was to
      investigate the modulatory effects of tofacitinib on serum GLS levels in patients
      with RA and GLS production in FLSs derived from patients with RA. METHODS: Six
      patients with RA who had failed therapy with at least one TNF inhibitor and were
      receiving tofacitinib therapy were included in the study. Serum samples were
      collected to measure CRP, MMP-3 and GLS expression. FLSs derived from patients
      with RA were cultured and stimulated by TNFalpha with or without tofacitinib. GLS
      expression levels were determined using reverse transcription-polymerase chain
      reaction (RT-PCR), EIA and immunocytochemistry, and signal transducer and
      activator of transcription (STAT) protein phosphorylation levels were determined
      by western blotting. RESULTS: Treatment with tofacitinib decreased serum GLS
      levels in all patients. GLS mRNA and protein expression levels were significantly
      increased by treatment with TNF-alpha alone, and these increases were suppressed
      by treatment with tofacitinib, which also inhibited TNF-alpha-induced STAT1
      phosphorylation. CONCLUSIONS: JAK/STAT activation plays a pivotal role in TNF
      alpha-mediated GLS up-regulation in RA. Suppression of GLS expression in FLSs has
      been suggested to be one of the mechanisms through which tofacitinib exerts its
      anti-inflammatory effects.

PMID- 29352847
TI  - Switching to biosimilar infliximab: real world data in patients with severe
      inflammatory arthritis.

PMID- 29352848
TI  - Association between perceived level of stress, clinical characteristics and
      psychopathological symptoms in women with systemic lupus erythematosus.
AB  - OBJECTIVES: To evaluate psychopathological status and stress level from a sample
      with SLE; compare mental functioning and stress levels between women with SLE and
      healthy women; determine whether disease duration, disease activity, cumulative
      organ damage and stress have an influence on psychopathological symptoms in SLE
      patients; and evaluate whether perception of stress is related to SLE severity.
      METHODS: We conducted a cross-sectional study of 425 participants; 202 women with
      SLE, with an average age (SD) of 36.61 (10.15), and 223 healthy women, with age
      matched controls. The assessment included the clinical characteristics (disease
      duration, SLE activity, cumulative organ damage, pharmacotherapy), the Symptom
      Checklist-90-Revised (SCL-90-R) and the Perceived Stress Scale. Descriptive,
      comparative, univariate and multivariate analysis were performed. RESULTS: SLE
      patients showed psychopathological alterations in the somatisation, obsessive
      compulsive and positive discomfort subscales of SCL-90-R. Women with SLE reported
      significantly higher scores on the psychopathological dimensions and perceived
      stress compared to healthy women, except for paranoid ideation. Disease duration,
      SLE activity, cumulative organ damage, and perceived stress were shown to be
      significant predictors of psychopathological manifestations, explaining a range,
      between 20 and 43%, of variance across SCL-90-R dimensions. Moreover, perceived
      stress was related to SLE activity, after controlling for psychopathological
      dimensions. CONCLUSIONS: The psychopathological manifestations in SLE appeared to
      be influenced by perceived stress, disease duration, disease activity and
      cumulative organ damage. In turn, perceived stress was associated with disease
      severity. This knowledge may contribute to a more comprehensive perspective of
      these manifestations in the SLE population in the clinical setting.

PMID- 29352849
TI  - Impact of vasculitis on employment and income.
AB  - OBJECTIVES: Work disability associated with rheumatic diseases accounts for a
      substantial financial burden. However, few studies have investigated disability
      among patients with vasculitis. The purpose of this study was to examine the
      impact of vasculitis on patient employment and income. METHODS: Patients enrolled
      in the Vasculitis Clinical Research Consortium (VCRC) Patient Contact Registry,
      living in the USA or Canada, and followed for >1 year post-diagnosis,
      participated in an online survey-based study. RESULTS: 421 patients with
      different systemic vasculitides completed the survey between June and December
      2015. The majority of patients were female (70%) and Caucasian (90%);
      granulomatosis with polyangiitis (GPA) was the most common type of vasculitis
      (49%), and the mean age at the time of diagnosis was 53 years. At the time of
      their diagnosis of vasculitis 76% of patients were working a paid job, 6% were
      retired, and 2% were on disability. Over the course of their disease, and with a
      mean follow-up of 8+/-6.4 years post-diagnosis, 26% of participants became
      permanently work disabled or had to retire early due to vasculitis. Variables
      that were independently associated with permanent work disability included work
      physicality, less supportive work environment, and symptoms such as respiratory
      disease, pain, and cognitive impairment. Overall, patients reported a mean
      productivity loss of 6.9% and income was reduced by a median of 45%. CONCLUSIONS:
      Due to their vasculitis, patients frequently suffer substantial limitations in
      work and productivity, and personal income loss.

PMID- 29352850
TI  - Ultrasound to detect involvement of vertebral artery in giant cell arteritis.

PMID- 29352851
TI  - Prostate cancer-associated polyarteritis nodosa: improvement of clinical
      manifestations after prostatectomy.

PMID- 29352852
TI  - Associations between the SLC22A12 gene and gout susceptibility: a meta-analysis.
AB  - OBJECTIVES: The aim of this study is to explore whether the polymorphisms of
      rs475688 and rs3825016 in the solute carrier family 22 member 12 (SLC22A12) gene
      are associated with the susceptibility to gout or hyperuricaemia. METHODS:
      Relevant studies were enrolled by searching databases systematically. The pooled
      odds ratios (ORs) with 95% confidence interval (CI) were used to evaluate the
      associations. Q-test and I2 statistics were used to evaluate the heterogeneity.
      Publication bias was evaluated using Begg's funnel plots and Egger regression
      test. RESULTS: A total of 7 articles involving 1216 patients and 1844 healthy
      controls were included in this meta-analysis. Significant association was
      detected between rs475688 polymorphism and gout susceptibility in three genetic
      models (C vs. T: OR=1.464, 95% CI 1.078-1.989, p=0.015; CC+CT vs. TT: OR=2.028,
      95% CI 1.488-2.763, p=0.000; CC vs. CT+TT: OR=2.226, 95% CI 1.746-2.838,
      p=0.000). Significant association was observed between rs3825016 polymorphism and
      hyperuricaemia susceptibility only in allelic comparison (C vs. T: OR=1.274, 95%
      CI 1.101-1.474, p=0.001). CONCLUSIONS: The rs475688 polymorphism is associated
      with gout susceptibility. The correlation between rs3825016 polymorphism of
      SLC22A12 and hyperuricaemia susceptibility is possible.

PMID- 29352853
TI  - Interferon regulatory factor 5 is a potential target of autoimmune response
      triggered by Epstein-barr virus and Mycobacterium avium subsp. paratuberculosis
      in rheumatoid arthritis: investigating a mechanism of molecular mimicry.
AB  - OBJECTIVES: Rheumatoid arthritis (RA) is a chronic disease characterised by a pro
      inflammatory cytokines linked erosive joint damage and by humoral and cellular
      response against a broad range of self-peptides. Molecular mimicry between
      Epstein-Barr virus (EBV), Mycobacterium avium subsp. paratuberculosis (MAP) and
      host peptides has long been regarded as an RA pathogenetic mechanism. Using
      bioinformatic analysis we identified high sequence homology among interferon
      regulatory factor 5 (IRF5), EBV antigen BOLF1 and MAP antigen MAP_4027. Our
      objective was to evaluate the presence in sera of RA patients of antibodies (Abs)
      directed against human homologous IRF5 cross-reacting with BOLF1 and MAP_4027.
      METHODS: Frequency of reactivity against IRF5424-434, BOLF1305-320 and MAP_402718
      32 was tested by indirect ELISA in sera from 71 RA patients and 60 healthy
      controls (HCs). RESULTS: RA sera show a remarkable high frequency of reactivity
      against IRF5424-434 in comparison to HCs (69% vs. 8%; p<0.0001). Similarly,
      seroreactivity against BOLF1305-320 was more frequently detected in RA sera than
      in HCs counterpart (58% vs. 8%; p<0.0001). Frequency of Abs against MAP_402718-32
      was 17% in RA sera vs. 5% in HCs with a p-value at the threshold level (p<0.051).
      Prevalence of Abs against at least one of the assessed epitopes reached 72% in RA
      patients and 15% among HCs. Levels of Abs in RA patients were significantly
      related to systemic inflammation. CONCLUSIONS: IRF5 is a potential autoimmune
      target of RA. Our results support the hypothesis that EBV and MAP infections may
      be involved in the pathogenesis of RA, igniting a secondary immune response that
      cross-reacts against RA self-peptides.

PMID- 29352854
TI  - Fc gamma receptor binding profile of anti-citrullinated protein antibodies in
      immune complexes suggests a role for FcgammaRI in the pathogenesis of synovial
      inflammation.
AB  - OBJECTIVES: Anti-citrullinated protein antibodies (ACPA) are highly specific for
      rheumatoid arthritis (RA). Here, we studied binding of ACPA-IgG immune complexes
      (IC) to individual Fc gamma receptors (FcgammaR) to identify potential effector
      mechanisms by which ACPA could contribute to RA pathogenesis. METHODS: ACPA-IgG1
      and control IgG1(IgG1 depleted of ACPA-IgG1) were isolated from plasma and
      synovial fluid (SF) of RA patients by affinity chromatography using CCP2
      peptides. Subsequently, IC were generated using fluorescently labelled F(ab')2
      fragments against the F(ab')2 region of IgG, or by using citrullinated
      fibrinogen. IC were incubated with FcgammaR-transfected CHO cell lines or
      neutrophils from healthy donors. FcgammaR binding of IC was analysed by flow
      cytometry in the presence or absence of specific blocking antibodies. RESULTS:
      ACPA-IgG1 IC predominantly bound to FcgammaRI and FcgammaRIIIA on FcgammaR
      transfected CHO cell lines, while much lower binding was observed to FcgammaRIIA
      and FcgammaRIIB. ACPA-IgG1 IC showed reduced binding to FcgammaRIIIA compared to
      control IgG1 IC, in line with enhanced ACPA-IgG1 Fc core-fucosylation.
      Neutrophils activated in vitro to induce de novo expression of FcgammaRI showed
      binding of ACPA-IgG IC, and blocking studies revealed that almost 30% of ACPA-IgG
      IC binding to activated neutrophils was mediated by FcgammaRI. CONCLUSIONS: Our
      studies show that ACPA-IgG1 IC bind predominately to activating FcgammaRI and
      FcgammaRIIIA, and highlight FcgammaRI expressed by activated neutrophils as
      relevant receptor for these IC. As neutrophils isolated from SF exhibit an
      activated state and express FcgammaRI in the synovial compartment, this IC
      binding could contribute to driving disease pathogenesis in RA.

PMID- 29352856
TI  - Facial Nerve Paralysis-A Rare Complication of Open Reduction of
      Zygomaticomaxillary Complex Fractures.
AB  - Facial nerve paralysis is an unusual formidable complication that can manifest
      after various maxillofacial surgeries, including open reduction of facial trauma.
      The branches more predisposed to such injury are the zygomatic and marginal
      mandibular branches. Zygomaticomaxillary complex (ZMC) fractures are frequently
      encountered in maxillofacial trauma. The facial nerve has not been described as
      endangered during ZMC surgery. Paralysis of the buccal branch after ZMC repair
      with delayed onset has been reported only once. This report describes a patient
      with immediate facial nerve paralysis after open reduction and internal fixation
      of an isolated ZMC fracture through an intraoral approach. This is a previously
      unreported rare complication after ZMC fracture repair that should be discussed
      as a possibility when obtaining preoperative consent.

PMID- 29352855
TI  - Risk of progression from subjective cognitive decline to mild cognitive
      impairment: The role of study setting.
AB  - INTRODUCTION: We compared risk of progression from subjective cognitive decline
      (SCD) to mild cognitive impairment (MCI) in an academic memory clinic versus a
      population-based study. METHODS: Older adults presenting at a memory clinic were
      classified as SCD (n = 113) or as noncomplainers (n = 82). Participants from a
      population study were classified as SCD (n = 592) and noncomplainers (n = 589)
      based on a memory complaint score. Annual follow-up performed for a mean of 3
      years. RESULTS: The adjusted hazard ratio for SCD was 15.97 (95% confidence
      interval: 6.08-42.02, P < .001) in the memory clinic versus 1.18 (95% confidence
      interval: 1.00-1.40, P = .047) in the population study, where reported "worry"
      about memory further increased SCD-associated risk for MCI. DISCUSSION: SCD is
      more likely to progress to MCI in a memory clinic than the general population;
      participants' characteristics vary across settings. Study setting should be
      considered when evaluating SCD as a risk state for MCI and dementia.

PMID- 29352857
TI  - Combining chemotherapy with PD-1 blockade in NSCLC.
AB  - Antitumor immunity relies on the ability of the immune system to recognize tumor
      cells as foreign and eliminate them. An effective immune response in this setting
      is due to surveillance of tumor-specific antigens that induce an adaptive immune
      response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors,
      specifically those targeting the programmed cell death-1 (PD-1)/programmed cell
      death ligand-1 (PD-L1) axis, have demonstrated promising activity in non-small
      cell lung cancer (NSCLC). However, there remains a crucial need for better
      treatment strategies for the majority of patients with advanced NSCLC,
      particularly in the frontline setting. Chemotherapy can increase antigenicity via
      immunogenic cell death (ICD) of tumor cells as well as also reduce "off target"
      immunosuppression in the tumor microenvironment (TME). Combining chemotherapy
      with PD-1 blockade harnesses the potential synergy between these agents and has
      led to encouraging results in the up-front treatment of NSCLC. In this review, we
      summarize the preclinical rationale behind these combinations and review recent
      trial data demonstrating their efficacy.

PMID- 29352858
TI  - Cardiac repair by epicardial EMT: Current targets and a potential role for the
      primary cilium.
AB  - Despite therapeutic advances that have prolonged life, myocardial infarction (MI)
      remains a leading cause of death worldwide and imparts a significant economic
      burden. The advancement of treatments to improve cardiac repair post-MI requires
      the discovery of new targeted treatment strategies. Recent studies have
      highlighted the importance of the epicardial covering of the heart in both
      cardiac development and lower vertebrate cardiac regeneration. The epicardium
      serves as a source of cardiac cells including smooth muscle cells, endothelial
      cells and cardiac fibroblasts. Mammalian adult epicardial cells are typically
      quiescent. However, the fetal genetic program is reactivated post-MI, and
      epicardial epithelial-to-mesenchymal transition (EMT) occurs as an inherent
      mechanism to support neovascularization and cardiac healing. Unfortunately,
      endogenous EMT is not enough to encourage sufficient repair. Recent developments
      in our understanding of the mechanisms supporting the EMT process has led to a
      number of studies directed at augmenting epicardial EMT post-MI. With a focus on
      the role of the primary cilium, this review outlines the newly demonstrated
      mechanisms supporting EMT, the role of epicardial EMT in cardiac development, and
      promising advances in augmenting epicardial EMT as potential therapeutics to
      support cardiac repair post-MI.

PMID- 29352859
TI  - Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in
      antimigraine therapy?
AB  - Migraine is a neurovascular disorder that involves activation of the
      trigeminovascular system and cranial vasodilation mediated by release of
      calcitonin gene-related peptide (CGRP). The gold standard for acute migraine
      treatment are the triptans, 5-HT1B/1D/(1F) receptor agonists. Their actions are
      thought to be mediated through activation of: (i) 5-HT1B receptors in cranial
      blood vessels with subsequent cranial vasoconstriction; (ii) prejunctional 5-HT1D
      receptors on trigeminal fibers that inhibit trigeminal CGRP release; and (iii) 5
      HT1B/1D/1F receptors in central nervous system involved in (anti)nociceptive
      modulation. Unfortunately, coronary arteries also express 5-HT1B receptors whose
      activation would produce coronary vasoconstriction; hence, triptans are
      contraindicated in patients with cardiovascular disease. In addition, since
      migraineurs have an increased cardiovascular risk, it is important to develop
      antimigraine drugs devoid of vascular (side) effects. Ditans, here defined as
      selective 5-HT1F receptor agonists, were developed on the basis that most of the
      triptans activate trigeminal 5-HT1F receptors, which may explain part of the
      triptans' antimigraine action. Amongst the ditans, lasmiditan: (i) fails to
      constrict human coronary arteries; and (ii) is effective for the acute treatment
      of migraine in preliminary Phase III clinical trials. Admittedly, the exact site
      of action is still unknown, but lasmiditan possess a high lipophilicity, which
      suggests a direct action on the central descending antinociceptive pathways.
      Furthermore, since 5-HT1F receptors are located on trigeminal fibers, they could
      modulate CGRP release. This review will be particularly focussed on the
      similarities and differences between the triptans and the ditans, their proposed
      sites of action, side effects and their cardiovascular risk profile.

PMID- 29352860
TI  - Towards targeting resolution pathways of airway inflammation in asthma.
AB  - Asthma is a chronic disorder characterized by persistent inflammation of the
      airways with mucosal infiltration of eosinophils, T lymphocytes, and mast cells,
      and release of proinflammatory cytokines and lipid mediators. The natural
      resolution of airway inflammation is now recognized as an active host response,
      with highly coordinated cellular events under the control of endogenous pro
      resolving mediators that enable the restoration of tissue homeostasis. Lead
      members of proresolving mediators are enzymatically derived from essential
      polyunsaturated fatty acids, including arachidonic acid-derived lipoxins,
      eicosapentaenoic acid-derived E-series resolvins, and docosahexaenoic acid
      derived D-series resolvins, protectins, and maresins. Functionally, these
      specialized pro-resolving mediators can limit further leukocyte recruitment,
      induce granulocyte apoptosis, and enhance efferocytosis by macrophages. They can
      also switch macrophages from classical to alternatively activated cells, promote
      the return of non-apoptotic cells to lymphatics and blood vessels, and help
      initiate tissue repair and healing. In this review, we highlight cellular and
      molecular mechanisms for successful resolution of inflammation, and describe the
      main specialized pro-resolving mediators that drive these processes. Furthermore,
      we report recent data suggesting that the pathobiology of severe asthma may
      result in part from impaired resolution of airway inflammation, including defects
      in the biosynthesis of these specialized pro-resolving mediators. Finally, we
      discuss resolution-based therapeutic perspectives.

PMID- 29352861
TI  - ERICA: age at menarche and its association with nutritional status.
AB  - OBJECTIVE: To estimate the mean age at menarche and its association with
      nutritional status in Brazilian adolescents. METHODS: The study sample included
      female adolescents aged 12-17 who participated in a multicenter, school-based,
      country-wide, cross-sectional study entitled The Study of Cardiovascular Risk in
      Adolescents (Estudo de Riscos Cardiovasculares em Adolescentes [ERICA]). Mean and
      median ages at menarche in Brazil were estimated. The association of age at
      menarche with sociodemographic data and nutritional status were described as
      means and their respective 95% confidence intervals. Survival analysis was used
      to assess the age at menarche according to nutritional status categories and the
      log-rank test was used to compare the medians. Bivariate and multivariate
      analyses were performed using Cox regression to verify the association between
      menarche and other variables. RESULTS: A total of 73,624 students were evaluated,
      comprising 40,803 girls, of whom 37,390 reported menarche at a mean age of 11.71
      years and a median of 12.41 years. Median age at menarche was lower in overweight
      and obese girls (p<0.001). The multivariate analysis showed that excess weight
      (HR=1.28; 95% CI 1.21-1.36; p<0.001) and studying in a private school (HR=1.06;
      95% CI 1.02-1.10; p=0.003) were associated with menarche. CONCLUSIONS: This is a
      pioneering study in Brazil with national and regional representativeness to
      estimate the mean and the median age of occurrence of menarche. Adolescents with
      excess weight had an earlier menarche than their peers, even after adjustment for
      confounding factors.

PMID- 29352862
TI  - Integrated care and the challenge of chronic illness.

PMID- 29352863
TI  - A chitin deacetylase of Podospora anserina has two functional chitin binding
      domains and a unique mode of action.
AB  - Chitosan is a structurally diverse biopolymer that is commercially derived from
      chitin by chemical processing, but chitin deacetylases (CDAs) potentially offer a
      sustainable and more controllable approach allowing the production of chitosans
      with tailored structures and biological activities. We investigated the CDA from
      Podospora anserina (PaCDA) which is closely related to Colletotrichum
      lindemuthianum CDA in the catalytic domain, but unique in having two chitin
      binding domains. We produced recombinant PaCDA in Hansenula polymorpha for
      biochemical characterization and found that the catalytic domain of PaCDA is also
      functionally similar to C. lindemuthianum CDA, though differing in detail. When
      studying the enzyme's mode of action on chitin oligomers by quantitative mass
      spectrometric sequencing, we found almost all possible sequences up to full
      deacetylation but with a clear preference for specific products. Deletion muteins
      lacking one or both CBDs confirmed their proposed function in supporting the
      enzymatic conversion of the insoluble substrate colloidal chitin.

PMID- 29352864
TI  - Rosin modified cellulose nanofiber as a reinforcing and co-antimicrobial agents
      in polylactic acid /chitosan composite film for food packaging.
AB  - Cellulose nanofiber (CNF) was modified by rosin and used as a reinforcement
      filler within a polylactic acid (PLA) matrix. The resulting film was then coated
      with chitosan (CHT) to prepare a two-layer composite film for antimicrobial food
      packaging. The FT-IR spectra of rosin modified CNF (R-CNF) displayed a clear peak
      at 1730cm-1, which confirmed the successful esterification of CNF by rosin. The R
      CNF showed a better dispersion in PLA matrix than CNF and the loading of R-CNF
      had a significant effect on the mechanical properties of the resulting film. A
      percolation network was formed when the R-CNF loading was 8%, where the composite
      film displayed optimum mechanical properties. The antimicrobial test showed that
      the R-CNF/PLA/CHT composite film exhibited excellent antimicrobial performance
      against E. coli and B. subtilis, which could be attributed to the synergistic
      antimicrobial effect of CHT and rosin.

PMID- 29352865
TI  - Antihyperlipidemic and hepatoprotective activities of polysaccharide fraction
      from Cyclocarya paliurus in high-fat emulsion-induced hyperlipidaemic mice.
AB  - The objective of this study was to analyse the structure of CPP-2, and to observe
      the pharmacological effects of CPP-2 on lipid metabolism and oxidative stress.
      CPP-2, eluted as two main fractions comprised of two polysaccharides with Mw of
      307 and 3.7kDa, was mainly consisted of rhamnose, mannose, glucose and galactose
      in a molar ratio of 1.00:0.78:3.22:0.45. The results showed that treatment with
      CPP-2 could improve blood lipid levels (TC, TG, HDL-C and LDL-C), liver lipid
      levels (TC and TG) and antioxidant status (SOD, T-AOC, GSH-PX, MDA and LPO). In
      addition, the histopathological observations of mice livers and the GPT
      activities indicated that CPP-2 could attenuate liver cell injury. The present
      findings demonstrated that CPP-2 might be effective in lowering lipid and
      protecting against HFE-induced hyperlipidemia and non-alcoholic fatty liver.

PMID- 29352866
TI  - Thermo-reversible supramolecular hydrogels of trehalose-type diblock
      methylcellulose analogues.
AB  - This paper describes the design and synthesis of new trehalose-type diblock
      methylcellulose analogues with nonionic, cationic, and anionic cellobiosyl
      segments, namely 1-(tri-O-methyl-cellulosyl)-4-[beta-d-glucopyranosyl-(1->4)-beta
      d-glucopyranosyloxymethyl]-1H-1,2,3-triazole (1), 1-(tri-O-methyl-cellulosyl)-4
      [(6-amino-6-deoxy-beta-d-glucopyranosyl)-(1->4)- 6-amino-6-deoxy-beta-d
      glucopyranosyloxymethyl]-1H-1,2,3-triazole (2), and 4-(tri-O-methyl
      cellulosyloxymethyl)-1-[beta-d-glucopyranuronosyl-(1->4)-beta-d
      glucopyranuronosyl]-1H-1,2,3-triazole (3), respectively. Aqueous solutions of all
      of the 1,2,3-triazole-linked diblock methylcellulose analogues possessed higher
      surface activities than that of industrially produced methylcellulose and
      exhibited lower critical solution temperatures, that allowed the formation of
      thermoresponsive supramolecular hydrogels at close to human body temperature.
      Supramolecular structures of thermo-reversible hydrogels based on compounds 1, 2,
      and 3 were investigated by means of scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). Detailed structure-property-function
      relationships of compounds 1, 2, and 3 were discussed. Not only nonionic
      hydrophilic segment but also ionic hydrophilic segments of diblock
      methylcellulose analogues were valid for the formation of thermo-reversible
      supramolecular hydrogels based on end-functionalized methylcellulose.

PMID- 29352867
TI  - Preparation, surface activity and colloidal properties of the ionic complex of
      chitosan with hexadecyl-oligo-oxyethylene hemisuccinate.
AB  - Chitosan polyelectrolyte complex with high surface activity has been prepared by
      salt complexation of chitosan with hexadecyl-oligo-oxyethylene hemisuccinate
      (HOS), an anionic surfactant. Physicochemical properties of chitosan-HOS complex
      can be explained by unusual structure of HOS which has the polyoxyethylene chain
      located between the polar carboxyl head group and the hydrophobic alkyl tail.
      Aqueous solutions of chitosan-HOS complex are structured systems with pronounced
      thixotropic properties. The effect of content of hydrophobic exchanged groups on
      the solution properties of chitosan-HOS complex and various factors controlling
      the stability of oil-in-water emulsions in the presence of chitosan-HOS complex
      are studied. The synergistic effect of the enhanced emulsifying ability of
      chitosan-HOS complexes is shown. The study discloses a possibility to produce an
      effective bio-compatible emulsifier based on chitosan-HOS complex.

PMID- 29352868
TI  - Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug
      nanogel for cancer detection and treatment.
AB  - Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug
      nanogels were designed for the tumor diagnosis and chemotherapy, by crosslinking
      the folate-terminated poly(ethylene glycol) (FA-PEG-NH2) and rhodamine B (RhB)
      terminated poly(ethylene glycol) (RhB-PEG-NH2) modified oxidized alginate (OAL-g
      PEG-FA/RhB) with cystamine (Cys), followed covalent conjugation of doxorubicin
      (DOX) via acid-labile Schiff base bond. Owing to the surface folic acid (FA)
      groups, disulfide crosslinking structure and Schiff base conjugation for DOX, the
      folate receptor (FR)-mediated targeting and pH/reduction dual responsive
      intracellular triggered release of DOX was achieved. The cytotoxicity and
      cellular uptake results clearly illustrated that most DOX was released and
      accumulated in the cell nuclei and killed the cancer cells efficaciously, due to
      the desirable targeting intracellular triggered release. Furthermore, the
      theranostic nanogels could be used for the real-time and noninvasive location
      tracking to cancer cells, owing to the pH-modulated fluorescence property of the
      pendant RhB groups.

PMID- 29352869
TI  - Positively charged gold nanoparticles capped with folate quaternary chitosan:
      Synthesis, cytotoxicity, and uptake by cancer cells.
AB  - In this study, we synthesized various quaternary chitosan derivatives and used
      them to stabilize gold nanoparticles (AuNPs). These chitosan derivatives
      comprised N-(2-hydroxy)propyl-3-trimethylammonium chitosan chloride (HTCC),
      folate-HTCC, galactosyl-HTCC, and their fluorescein isothiocyanate-conjugated
      derivatives. Various positively surface-charged AuNPs were prepared under
      alkaline conditions using glucose as a reducing agent in the presence of the HTCC
      derivatives (HTCCs). The effects of the concentration of NaOH, glucose, and HTCCs
      on the particles size, zeta potential, and stability were studied in detail. Cell
      cycle assays verify that none of the HTCCs or HTCCs-AuNPs was cytotoxic to human
      umbilical vein endothelial cells. Flow cytometry analysis showed that the folate
      HTCC-AuNPs were internalized in Caco-2, HepG2, and HeLa cancer cells to a
      significantly greater extent than AuNPs without folate. But, galactosyl HTCC
      AuNPs only showed high cell uptake by HepG2 cells.

PMID- 29352870
TI  - Radiation grafting: A voyage from bio-waste corn husk to an efficient
      thermostable adsorbent.
AB  - The initiator free environmentally benign gamma radiation is employed to graft
      poly-acrylic acid (PAA) onto the widely produced bio-waste corn husk to develop
      promising, cheap, efficient and reusable adsorbent (AAc-g-husk) having specific
      adsorption capacity of 1682.7mgg-1 of methylene blue (MB) at pH 9.0 and 320K. The
      most suitable grafting yield is found by optimizing absorbed dose, dose rate and
      concentrations of monomer, Mohr's salt and inorganic acid. The inter-planar
      hydrogen bonding among (002) planes of cellulose in the husk decreases after
      diversifying grafting of PAA on ad-axial, ribs and micro-fibrils surfaces of the
      corn husks. The chemically and structurally modified AAc-g-husk shows superior
      thermal stability. The mechanism of MB dye adsorption by AAc-g-husk has been
      discussed through six two-parameters adsorption isotherm and ten three-parameters
      adsorption isotherm models at three different temperatures (300, 310 and 320K),
      seven kinetic models at room temperature, FT-IR and desorption studies in
      different solvent compositions.

PMID- 29352871
TI  - A novel approach for fabricating nanocomposite materials by embedding stabilized
      core-shell micelles into polysaccharide cryogel matrix.
AB  - We report a novel approach for fabricating nanocomposite polysaccharide-based
      carriers for sustained delivery of poorly-water-soluble drugs by embedding
      stabilized core-shell micelles (SPM) possessing hydrophobic cores into super
      macroporous hydroxypropyl cellulose (HPC) cryogels. Firstly, nano-sized SPM were
      synthesized by loading and photochemical crosslinking of
      pentaerythritoltetraacrylate (PETA) in poly(ethylene oxide)-b-poly(propylene
      oxide)-b-poly(ethylene oxide) (PEO19PPO29PEO19) core-shell micelles. Next, HPC
      cryogels containing different amount of SPM were fabricated by combination of
      cryogenic treatment and photo-crosslinking. A crosslinking agent, N,N'
      methylenebisacrylamide, was used to enhance the density of polymer network. The
      effect of SPM concentration on gel fraction yield, swelling degree, cryogel
      morphology and mechanical properties were studied. Nanocomposite cryogels were
      loaded with curcumin and their encapsulation efficiency and drug release profile
      as a function of SPM content were investigated. The cytotoxic effect of blank and
      curcumin loaded nanocomposite cryogels was assessed as well.

PMID- 29352872
TI  - Preparation and testing of a tetra-amine copper(II) chitosan bead system for
      enhanced phosphate remediation.
AB  - A tetra-amine copper(II) chitosan bead system (TAC@CS composite beads) was
      developed by grafting tetra-amine copper(II) (TAC) with chitosan (CS) and
      utilized for phosphate removal. The prepared TAC@CS composite beads possess
      enhanced phosphate sorption capacity (SC) of 41.42 +/- 0.071 mg/g than copper
      grafted chitosan (Cu@CS) composite, TAC and chitosan which were found to be 37.01
      +/- 0.803, 33.20 +/- 0.650 and 7.24 +/- 0.059 mg/g respectively. In batch mode,
      various adsorption influencing parameters like contact time, initial phosphate
      concentration, solution pH, co-anions and temperature were optimized for maximum
      phosphate sorption. The prepared adsorbents were characterized by FTIR, XRD, UV
      Visible, SEM and EDAX analysis. The adsorption isotherms and thermodynamic
      parameters of the adsorbent were studied. The feasible phosphate uptake mechanism
      of TAC@CS biocomposite beads was reported. The reusability studies of TAC@CS
      composite beads were carried out using NaOH as elutant. The suitability of TAC@CS
      composite beads at field conditions was tested with phosphate contaminated field
      water samples collected from nearby areas of Dindigul district.

PMID- 29352873
TI  - Electrospray-assisted drying of live probiotics in acacia gum microparticles
      matrix.
AB  - Acacia gum solution was employed as a carrier for electrospray-assisted drying of
      probiotic cells. To optimize the process, effect of gum concentration, thermal
      sterilization as a prerequisite for microbial studies, and surfactant addition on
      physical properties of feed solution was investigated. Increasing gum
      concentration from 20 to 40 wt.% led to a viscosity increase, whilst surface
      tension did not change meaningfully and electrical conductivity declined after an
      increasing trend up to 30 wt.% of the gum. Thermal sterilization increased the
      viscosity without any significant effect on the conductivity and surface tension.
      Surfactant addition reduced the surface tension and conductivity but the
      viscosity increased. Highly uniform particles were formed by electrospray
      assisted drying of autoclaved 35 wt.% acacia gum solution containing 1 wt.% Tween
      80. Thermal sterilization and surfactant addition improved electrospray-ability
      of acacia gum solution. Bacterial count showed that more than 96 percent of
      probiotic cells passed the process viably.

PMID- 29352874
TI  - 2,3-Di-O-sulfo glucuronic acid: An unmodified and unusual residue in a highly
      sulfated chondroitin sulfate from Litopenaeus vannamei.
AB  - The occurrence of a natural and unmodified highly sulfated chondroitin sulfate
      from Litopenaeus vannamei heads (sCS) is herein reported. Its partial digestion
      by Chondroitinases AC and ABC together with its electrophoretic migration profile
      revealed it as a highly sulfated chondroitin sulfate despite its average
      molecular weight being similar to CSA. Using orthogonal 1D/2D NMR experiments,
      the anomeric signals (delta 4.62/106.0) corresponding to unusual 2,3-di-O-Sulfo
      GlcA (~36%), U33S (delta 4.42/84.1, ~63%) and U22S (4.12/80.1, ~50%)
      substitutions were confirmed. In addition, non-sulfated GlcA (delta 4.5/106.3)
      linked to 4-O- (A14S, 36%) or 6-O-Sulfo (A16S, 28%) GalNAc (delta 4.64/103.5) was
      observed. Although the biological role of sCS in shrimp is unknown, its influence
      on hemostasis was also demonstrated. The sCS identification brings to light new
      questions about the hierarchical model of GAGs biosynthesis and contributes to
      the better understanding of the subtle relationship between GAGs structure and
      function.

PMID- 29352875
TI  - Combined effect of sodium carboxymethyl cellulose, cellulose nanofibers and
      drainage aids in recycled paper production process.
AB  - The present work shows the suitability of using recovered cardboard boxes for the
      development of high-performance papers through the use of cellulose nanofibers
      (CNF) and sodium carboxymethyl cellulose (CMC-Na). CNF were prepared by enzymatic
      hydrolysis using bleached kraft hardwood pulp, while a commercial grade of CMC-Na
      was used. Both were added in bulk together with polyethylenimine (PEI) as wet-end
      additive to improve pulp drainability. The combination of 3 wt% CNF and 7.5 wt%
      CMC-Na double the breaking length of paper. In addition, the use of 0.4 wt% of
      PEI significantly decreased the Schopper - Riegler degree, while mechanical
      properties remained almost at the same level. It was found that it is possible to
      recover and even increase the properties of recycled papers, with the added
      advantage that no structural damages were caused on the fibres, increasing the
      life span and recyclability of paper products.

PMID- 29352876
TI  - Structural characterization and macrophage activation of a hetero-galactan
      isolated from Flammulina velutipes.
AB  - We isolated and purified a new polysaccharide (WFVP-N-b1) with a molecular weight
      of 20 kDa from Flammulina velutipes. Results showed that WFVP-N-b1 is composed of
      an alpha (1 -> 6)-linked D-galactan backbone and branched at the O-2 of its Galp
      residues by an alpha-D-(1 -> 6)-linked Manp attached to t-beta-D-Glcp or t-alpha
      D-Fucp side chains. WFVP-N-b1 can significantly induce cytokines secretion and
      release of toxic molecules. On a cellular level, WFVP-N-b1 is recognized by Toll
      like receptor 4 (TLR4). Thereby, the hetero-galactan increased the
      phosphorylation of mitogen-activated protein kinases (MAPKs) and Akt, promoted
      degradation of IkappaB-alpha and the nuclear translocation of the NF-kappaB p65
      subunit. Importantly, our results indicate that WFVP-N-b1 activated macrophage is
      mediated by autophagy, as blockade of WFVP-N-b1-induced autophagy by Baf-A1
      significantly decreases macrophage activation. This is the first report that
      hetero-galactan-induced macrophage activation is mediated by autophagy.
      Collectively, WFVP-N-b1 activated RAW264.7 cells through MAPKs, autophagy, and
      Akt/NF-kappaB signaling pathways via TLR4 receptor.

PMID- 29352877
TI  - Valorization of peanut shells: Manufacture of bioactive oligosaccharides.
AB  - Peanut shells were subjected to non-isothermal aqueous treatments to cause the
      partial breakdown of hemicelluloses into soluble oligosaccharides and lignin
      derived compounds with high antioxidant activity. The effects of temperature on
      the chemical composition of the substrate and soluble reaction products were
      assessed. Under selected conditions (210 degrees C, severity=4.09), the overall
      amount of poly- and oligo- saccharides present in the liquid phase reached
      9.8g/L. This solution was refined by consecutive stages of discontinuous
      diafiltration, yielding a refined product containing about 72.4wt% of oligomers
      at a global yield of 8.5kg/100kg oven-dry PS. The purified products were
      characterized by HPLC, MALDI-TOF-MS and FTIR, confirming the major reaction
      products were saccharides made up of xylose with degrees of polymerization up to
      17, substituted with acetyl and methylglucuronosyl groups, for which a number of
      pharmaceutical and food applications have been proposed. Solubilization of
      hemicelluloses in the treatments resulted in the production of solids enriched in
      cellulose and lignin suitable for further applications.

PMID- 29352878
TI  - In vitro fermentation of Cookeina speciosa glucans stimulates the growth of the
      butyrogenic Clostridium cluster XIVa in a targeted way.
AB  - Dietary fiber chemical and physical structures may be critical to the
      comprehension of how they may modulate gut bacterial composition. We purified
      insoluble polymers from Cookeina speciosa, and investigated its fermentation
      profile in an in vitro human fecal fermentation model. Two glucans, characterized
      as a (1 -> 3),(1 -> 6)-linked and a (1->3)-linked beta-D-glucans were obtained.
      Both glucans were highly butyrogenic and propiogenic, with low gas production,
      during in vitro fecal fermentation and led to distinct bacterial shifts if
      compared to fructooligosaccharides. Specific increases in Bacteroides uniformis
      and genera from the Clostridium cluster XIVa, such as butyrogenic Anaerostipes
      and Roseburia were observed. The (1 -> 3)-linked beta-D-glucan presented a faster
      fermentation profile compared to the branched (1 -> 3),(1 -> 6)-linked beta-D
      glucan. Our findings support the view that depending on its fine chemical
      structure, and likely its insoluble nature, these dietary fibers can be utilized
      to direct a targeted promotion of the intestinal microbiota to butyrogenic
      Clostridium cluster XIVa bacteria.

PMID- 29352879
TI  - Structural characterization and in vitro fermentation of a novel polysaccharide
      from Sargassum thunbergii and its impact on gut microbiota.
AB  - The aim of the present study was to investigate structural characteristic and in
      vitro fermentation of a novel polysaccharide named ST-P2 from Sargassum
      thunbergii by human fecal inoculums, and its impact on human colonic microbiota.
      The results showed that ST-P2 was homogeneous with molecular weight of 48,788 Da,
      and consisted of arabinose, galactose, glucose, xylose, and mannose. The main
      linkage types were identified as (1 -> 5)-alpha-L-Araf, (1 -> 3)-alpha-L-Manp, (1
      -> 3,6)-beta-D-Galp, (1 -> 6)-alpha-D-Glcp, and (1 -> 3)-beta-D-Xylp,
      respectively. After 48 h fermentation, 67.83 +/- 1.15% of total carbohydrate was
      utilized by colonic microbiota. The pH value in the fecal culture significantly
      decreased from 6.09 +/- 0.11 to 4.70 +/- 0.04. The concentrations of total short
      chain fatty acids, acetic, propionic, n-butyric and n-valeric acids significantly
      increased compared to the blank. ST-P2 could remarkably modulate the composition
      and abundance of beneficial microbiota. These results suggest that ST-P2 could
      potentially be a functional food aimed at promoting the gut health.

PMID- 29352880
TI  - Preparation of chitosan sulfate and vesicle formation with a conventional
      cationic surfactant.
AB  - Chitosan of high molecular weight and 85% deacetylation was used to prepare
      chitosan sulfate (CHS) by employing an industrial recognized green and highly
      reactive sulfating agent gas SO3. FT-IR and solid-state CP-MAS 13C NMR spectra
      confirmed that sulfate groups were successfully introduced into chitosan chains
      with a sulfur content of 16.50% and the substitution degree of 1.75 according to
      the results of elemental analysis. The aggregation behavior of the mixture of
      chitosan sulfate polyelectrolyte and oppositely charged surfactant
      cetyltrimethylammonium bromide (CTAB) was characterized by surface tension,
      steady-state fluorescent, turbidity, zeta potential and transmission electron
      microscopy. The results indicate that the CHS/CTAB mixture has pretty high
      surface activity and low critical aggregation concentration. The CHS/CTAB mixture
      successively forms spherical aggregates, precipitation, vesicles and micelle
      aggregates coated by CHS chains by increasing surfactant concentration due to the
      cooperative hydrophobic and electrostatic interactions.

PMID- 29352881
TI  - Carbon nanotube-modified oxidized regenerated cellulose gauzes for hemostatic
      applications.
AB  - Functionalized carbon nanotubes have recently received interest because of their
      unique properties, especially in the biomedical field. In this research,
      unmodified multiwalled carbon nanotubes (MWCNTs), and functionalized carbon
      nanotubes with amino groups (MWCNTs-NH2) and carboxyl groups (MWCNTs-COOH) were
      grafted to oxidized regenerated cellulose (ORC) gauze to fabricate novel
      functionalized ORC, and the performance of the functionalized gauze was
      investigated. The functionalized ORC was characterized by FT-IR, XPS and SEM,
      which showed the different kinds of CNTs grafted on its surface. The XPS results
      demonstrated the successful incorporation of functionalized MWCNTs in the active
      layer of modified ORC gauze. Meanwhile, the specific surface area of the CNTs
      modified functionalized ORC gauze was improved in varying degrees, whereas the
      porosity was slightly decreased. Furthermore, hydrophilicity experiment results
      presented a significant increment in water uptake of the functionalized CNTs
      grafted to the surface of the ORC gauze. Results of the hemostatic performance
      test on rabbit ear artery and liver showed that compared with the original ORC
      gauze, the bleeding time was significantly reduced when using the functionalized
      CNTs modified ORC hemostatic gauze. Moreover, the results also showed that the
      MWCNTs-COOH/ORC functionalized gauze had outstanding hemostatic efficiency.

PMID- 29352882
TI  - Conductive bacterial cellulose-polyaniline blends: Influence of the matrix and
      synthesis conditions.
AB  - Bacterial cellulose/polyaniline (BC/PANi) blends present a great potential for
      several applications. The current study evaluates the impact of using different
      BC matrixes (drained, freeze-dried and regenerated) and different synthesis
      conditions (in situ and ex situ) to improve the inherent properties of BC, which
      were monitored through FTIR-ATR, EDX, XRD, SEM, AFM, swelling, contact angle
      measurement and IGC. The employment of in situ polymerization onto drained BC
      presented the most conductive membrane (1.4 * 10-1 S/cm). The crystallinity,
      swelling capacity, surface energy and acid/base behavior of the BC membranes is
      substantially modified upon PANi incorporation, being dependent on the BC matrix
      used, being the freeze-dried BC blends the ones with highest crystallinity (up to
      54%), swelling capacity (up to 414%) and surface energy (up to 75.0 mJ/m2).
      Hence, this work evidenced that the final properties of the BC/PANi blends are
      greatly influenced by both the BC matrixes and synthesis methods employed.

PMID- 29352884
TI  - Designed cellulose nanocrystal surface properties for improving barrier
      properties in polylactide nanocomposites.
AB  - Nanocomposites are an opportunity to increase the performance of polymer
      membranes by fine-tuning their morphology. In particular, the understanding of
      the contribution of the polymer matrix/nanofiller interface to the overall
      transport properties is key to design membranes with tailored selective and
      adsorptive properties. In that aim, cellulose nanocrystals (CNC)/polylactide
      (PLA) nanocomposites were fabricated with chemically designed interfaces, which
      were ensuring the compatibility between the constituents and impacting the mass
      transport mechanism. A detailed analysis of the mass transport behaviour of
      different permeants in CNC/PLA nanocomposites was carried out as a function of
      their chemical affinity to grafted CNC surfaces. Penetrants (O2 and cyclohexane),
      which were found to slightly interact with the constituents of the
      nanocomposites, provided information on the small tortuosity effect of CNC on
      diffusive mass transport. The mass transport of water (highly interacting with
      CNC) and anisole (interacting only with designed CNC surfaces) exhibited non
      Fickian, Case II behaviour. The water vapour caused significant swelling of the
      CNC, which created a preferential pathway for mass transport. CNC surface
      grafting could attenuate this phenomenon and decrease the water transport rate.
      Anisole, an aromatic organic vapour, became reversibly trapped at the
      specifically designed CNC/PLA interface, but without any swelling or creation of
      an accelerated pathway. This caused the decrease of the overall mass transport
      rate. The latter finding could open a way to the creation of materials with
      specifically designed barrier properties by designing nanocomposites interfaces
      with specific interactions towards permeants.

PMID- 29352883
TI  - The use of starch azure for measurement of alpha-amylase activity.
AB  - Despite being widely used, there is no standard protocol for alpha-amylase
      activity measurement with starch azure substrate. Boiling pre-treatment of starch
      azure suspension increased the reaction rate of hydrolysis catalysed by human
      salivary alpha-amylase (HSA) or porcine pancreatic alpha-amylase (PPA) and the
      sensitivity of spectrophotometric activity measurement has been improved. Kinetic
      constants, KM, and vmax, obtained from parallel isothermal titration calorimetric
      (ITC) measurements on natural and starch azure revealed, that the blue starch
      derivative does not differ significantly from its natural counterpart from
      kinetic point of view. Interestingly, substrate inhibition was observed in starch
      azure hydrolysis characterised by dissociation constants 49 mg/mL and 16.4 mg/mL
      for HSA and PPA, respectively. In this work a new protocol has been suggested for
      alpha-amylase activity measurement using boiled insoluble starch azure as
      substrate at 5 mg/mL concentration.

PMID- 29352885
TI  - Synthesis of stimuli-responsive chitosan-based hydrogels by Diels-Alder cross
      linking 'click' reaction as potential carriers for drug administration.
AB  - Stimuli-responsive chitosan-based hydrogels for biomedical applications using the
      Diels-Alder reaction were prepared. Furan modified chitosan (Cs-Fu) was cross
      linked with polyetheramine derived bismaleimide at different equivalent ratios in
      order to determine the effect in the swelling and release properties on the final
      CsFu:BMI hydrogels. The Diels Alder cross-linking reaction was monitored by UV
      vis spectroscopy and rheological measurements. Both the sol-gel transition value
      and the final storage modulus for the different formulations were similar and
      close to 40 min and 400 Pa, respectively. On the contrary, the swelling degree
      was found to be strongly dependent on the amount of bismaleimide, mainly in
      acidic medium, where the increased cross-linking reduced the swelling value in
      25%, but maintaining the sustained drug release in the simulated gastrointestinal
      environment. Our study suggested that these DA-cross-linked chitosan hydrogels
      could be potential carriers for targeted drug administration.

PMID- 29352887
TI  - The development of an alginate/polycaprolactone composite scaffold for in situ
      transfection application.
AB  - Alginate and polycaprolactone (PCL) were coelectrospun using a dual-jet system to
      prepare composite nanofibers in defined ratios, and hence both chemical
      properties and hydrophobicity of scaffolds can be manipulated. These nanofibers
      were applied in gene immobilization: positively charged polyethyleneimine
      (PEI)/DNA polyplexes were adsorbed onto anionic alginate fibers, and the higher
      ratios of alginate resulted in the more immobilized nonviral vectors. Through the
      incorporation of PCL, biocompatibility of scaffolds was highly improved. Finally,
      these scaffolds were used for in situ transfection application. Compared to pure
      alginate fibers, composite fibers not only successfully transferred target genes
      to adhered cells but also enhanced cell morphology and viability, suggesting that
      alginate/PCL nanofibers were multifunctional with gene delivery capability and
      biocompatibility, and the manipulation of their composition can balance and
      optimize both requirements. To our knowledge, this approach might be the first
      one using electrostatic interactions to immobilize genes onto nanofibrous
      scaffolds for in situ transfection application.

PMID- 29352886
TI  - Aldehyde-functionalized chitosan-montmorillonite films as dynamically-assembled,
      switchable-chemical release bioplastics.
AB  - Temporal release of synergistic and/or complementary chemicals (e.g.: drugs) is
      recognized as extremely challenging because of their frequently intertwined
      kinetic delivery and presently, straightforward concepts enabling to circumvent
      this bottleneck are missing in the open literature. In this framework, we report
      herein on aldehyde-functionalized, transparent and flexible chitosan
      montmorillonite hybrid films that act as a new generation of eco-friendly,
      controlled-chemical release bioplastics. These dynamically-assembled
      nanomaterials are designed by a ternary assembly from biowaste derived chitin
      biopolymer, aromatic aldehydes and layered clay nanoparticles. On the basis of
      their geometrical and conformational properties, the oxygenated groups on the
      grafted aromatics interact preferentially with either the base Schiff belonging
      to the carbohydrate (via intramolecular CNHO-Ar known as "imine clip") or with
      the hydroxyl groups belonging to the clay surface (via intermolecular Si-OHO-Ar).
      The exfoliated clay nanoparticles within the carbohydrate polymer enables either
      accelerating or slowing down of the imine (CN) hydrolysis depending on the
      interaction of the conjugated aromatics. This provides the driving force for fine
      tuning host-guest interactions at the molecular level and constitutes an entry
      toward subtle discrimination of different chemicals (e.g. complementary
      fertilizers, synergistic drugs) during their sequential release.

PMID- 29352888
TI  - Production of cellulose nanoparticles from blue agave waste treated with
      environmentally friendly processes.
AB  - Tequila elaboration leaves two main byproducts that are undervalued (bagasse and
      leaves). Organosolv pulping and Total Chlorine Free bleaching were integrated to
      obtain cellulose fibers from agricultural waste which consisted of blue agave
      bagasse and leaf fibers; together they represent a green process which valorizes
      biomass waste. The obtained celluloses were characterized by FT-IR, colorimetry,
      and SEM and their extraction yields were evaluated. These celluloses were used to
      produce cellulose nanocrystals and cellulose nanofibers. First, an acid
      hydrolysis was performed in a sonication bath to induce cavitation during the
      reaction to produce cellulose nanocrystals. Then a high-pressure homogenization
      was selected to produce cellulose nanofibers. These nanocelluloses were
      characterized by powder XRD, Nanosizer, zeta potential, NMR, and electronic
      microscopy. Results showed that cellulose from organosolv pulps bleached with TCF
      bleaching is suitable for nanocellulose production. Moreover, the use of a new
      step to separate cellulose nanocrystals resulted in yields almost doubling
      traditional yields, while the rest of the properties remained within the
      expected.

PMID- 29352889
TI  - Cellulose nanocrystals (CNCs) with different crystalline allomorph for oil in
      water Pickering emulsions.
AB  - In recent years, nanocelluloses have attracted a lot of interests as promising
      stabilizers for Pickering emulsion particularly in food, cosmetics and
      pharmaceutics industries. In this work, two cellulose nanocrystals (named CNCs-I
      and CNCs-II) with different crystalline allomorph were investigated as
      stabilizers for oil-water Pickering emulsion. CNCs were prepared by sulfuric acid
      hydrolysis of unmodified and mercerized microcrystalline cellulose (MCC),
      respectively. CNCs-I was needle-like particles (length - 200 nm, width - 16.4
      nm), while CNCs-II was individual granules (length - 18.8 nm, width - 10.9 nm)
      with ellipsoid shapes. Both CNCs had surface charge density higher than 0.1
      e/nm2. Pickering emulsions stabilized by CNCs-I had larger emulsion ratio, two
      times smaller droplet size and superior performance of stability than CNCs-II. It
      is concluded that crystalline allomorph of CNCs played more dominating roles to
      the stabilization of Pickering emulsion than morphologies of CNCs themselves in
      this work, and CNCs-II is not the good candidates as stabilizer for Pickering
      emulsion compared to CNCs-I.

PMID- 29352890
TI  - Nanocrystalline cellulose as an eco-friendly reinforcing additive to polyurethane
      coating for augmented anticorrosive behavior.
AB  - Nanocrystalline cellulose (NCC) and micro-powdered cellulose (MPC) were extracted
      from rice straw by mechanical and alkali treatment methods, then characterized
      via infrared spectroscopy and dynamic light scattering. A series of polyurethane
      nanocrystalline cellulose composite (PNCCC) and polyurethane micro-powdered
      cellulose composite (PMPCC) coatings were prepared with various loading levels of
      NCC and MPC from 0.5 to 2.0 wt.%, and the coatings were applied onto the
      pretreated mild steel substrate at room temperature. The results showed that the
      NCC and MPC influenced positively the studied properties of the polyurethane
      coating; furthermore the most pronounced anticorrosive properties were obtained
      at 1 wt.% NCC and MPC, as confirmed by open circuit potential (OCP) study,
      electrochemical impedance spectroscopy (EIS) study and salt spray test. However,
      the optimum enhancement of mechanical properties was found at 1.5 wt.% loading
      level, after which further loading of NCC and MPC led to the reduction in the
      mechanical properties.

PMID- 29352891
TI  - Efficient gene delivery by oligochitosan conjugated serum albumin: Facile
      synthesis, polyplex stability, and transfection.
AB  - Chitosan and its derivatives have shown to be potential gene carriers with
      biocompatiblility and safety. However, their practical delivery is far from being
      ideal because of the low transfection efficiency. The present work describes the
      potential of a natural protein, bovine serum albumin (BSA), conjugated with a
      natural oligosaccharide, oligochitosan (OC), as a considerable promising approach
      for a safe and efficient non-viral gene delivery vector. The FTIR spectra proved
      the effective conjugation of BSA with OC through covalent bond. The condensation
      ability of plasmid DNA (pDNA) with a BSA-OC biopolymer was analyzed by gel
      retardation assay, competition binding assay, and dynamic light scattering used
      to measure the nanoparticle size. In addition, the BSA-OC biopolymer showed the
      protection of pDNA from enzymatic degradation by DNase I and showed good
      stability when exposed to 50% fetal bovine serum. The transfection efficiency was
      evaluated in the presence of 10% serum-supplemented media or serum-free media on
      three kinds of mammalian cells. Our results showed that the BSA-OC biopolymer is
      a good non-viral vehicle for gene delivery. We investigated the parameters such
      as the pDNA payload, temperature, incubating duration, and biopolymer/pDNA ratio
      on the transfection efficiency. This hybrid vehicle had the ability to transfect
      90% of cells and to maintain 80% of cell viability. The aforementioned results
      suggest that the facile synthesis of the BSA-OC biopolymer could overcome the
      cytotoxicity problem and transfection barriers during in vitro gene delivery.

PMID- 29352892
TI  - Synergistic effect of carbon nanotubes and graphene for high performance
      cellulose acetate membranes in biomedical applications.
AB  - Comparative evaluation of innovative combinations of three types of carbon
      nanomaterial (CNM) highlighted membranes with important potential for biomedical
      applications. Non-solvent induced phase separation coupled with ultrasound
      technique was used to generate membranes comprised of (i) cellulose
      acetate/ammonia functionalized carbon nanotubes (CA/CNT), (ii) cellulose
      acetate/ammonia functionalized graphene oxide (CA/GO), and (iii) cellulose
      acetate/CNT-GO. Structural, topographical and thermal features as well as water
      and ethanol permeation, bovine serum albumin (BSA) and haemoglobin (Hb) rejection
      were evaluated. Biocompatibility in terms of cytotoxicity, cell proliferation and
      adhesion were explored using a 3T3E1 cell line. The formation of amorphous
      structures, within which the CNMs were well dispersed, facilitated the
      development of smoother topographies. Addition of CNMs generated morphological
      changes influencing a decrease in water and ethanol fluxes. Furthermore, CNMs
      concentrated within the membrane skin layer exhibited repellent effects against
      BSA and Hb molecules and excellent cytocompatibility.

PMID- 29352893
TI  - Preparation and characterization of tree-like cellulose nanofiber membranes via
      the electrospinning method.
AB  - A novel tree-like cellulose nanofiber membrane was controllably fabricated via
      the electrospinning method by adding certain amount of tetra butyl ammonium
      chloride (TBAC) into the cellulose acetate solution followed by a deacetylation
      treatment process. The morphological structure, material structure and air
      filtration performance of both the cellulose and the cellulose acetate tree-like
      nanofiber membranes were characterized. Water contact angles, mechanical
      properties, and air filtration properties were also evaluated. The air filtration
      efficiency of cellulose acetate tree-like nanofiber membrane can reached 99.58%,
      and the eventually cellulose tree-like membrane still maintain 98.37%. The
      eventual cellulose tree-like nanofiber membranes exhibited small pore size,
      excellent hydrophilicity, good solvent resistance and preferable mechanical
      property. The small average pore size caused by the tree-like structure and the
      strong resistance to organic solvent can make it a potential candidate for the
      membrane separation.

PMID- 29352894
TI  - A novel wound dressing based on a Konjac glucomannan/silver nanoparticle
      composite sponge effectively kills bacteria and accelerates wound healing.
AB  - A novel Konjac glucomannan/silver nanoparticle (KGM/AgNP) composite sponge was
      successfully prepared via a simple 2-step method for biomedical applications as
      wound-healing materials. First, AgNPs were prepared with green deoxidizer egg
      white. Then, KGM powder was added to the AgNP solution and stirred vigorously,
      and the composite sponge was obtained by freeze-drying. The KGM/AgNP composite
      sponge showed excellent water absorption and water retention, and considerable
      mechanical properties. KGM/AgNP composite sponges displayed good antibacterial
      activity against test microorganisms. In vitro cytocompatibility testing showed
      that L929 cells could survive well in the presence of KGM/AgNPs, indicating that
      KGM/AgNPs have good cytocompatibility. Animal models showed that the KGM/AgNP
      composite sponges effectively accelerated wound healing, and histological
      findings showed that they promoted fibroblast growth and accelerated
      epithelialization. The experimental results showed that KGM/AgNP composite
      sponges have great potential in promoting wound healing.

PMID- 29352895
TI  - Sequencing the oligosaccharide pool in the low molecular weight heparin
      dalteparin with offline HPLC and ESI-MS/MS.
AB  - Low molecular weight heparins (LMWHs) are widely used anticoagulant drugs. The
      composition and sequence of LMWH oligosaccharides determine their safety and
      efficacy. The short oligosaccharide pool in LMWHs undergoes more depolymerization
      reactions than the longer chains and is the most sensitive indicator of the
      manufacturing process. Electrospray ionization tandem mass spectrometry (ESI
      MS/MS) has been demonstrated as a powerful tool to sequence synthetic heparin
      oligosaccharide but never been applied to analyze complicated mixture like LMWHs.
      We established an offline strong anion exchange (SAX)-high performance liquid
      chromatography (HPLC) and ESI-MS/MS approach to sequence the short
      oligosaccharides of dalteparin sodium. With the help of in-house developed MS/MS
      interpretation software, the sequences of 18 representative species ranging from
      tetrasaccharide to octasaccharide were obtained. Interestingly, we found a novel
      2,3-disulfated hexauronic acid structure and reconfirmed it by complementary
      heparinase digestion and LC-MS/MS analysis. This approach provides
      straightforward and in-depth insight to the structure of LMWHs and the reaction
      mechanism of heparin depolymerization.

PMID- 29352896
TI  - Biological activities and pharmaceutical applications of polysaccharide from
      natural resources: A review.
AB  - Pharmacotherapy using natural substances can be currently regarded as a very
      promising future alternative to conventional therapy. As biological
      macromolecules, polysaccharide together with protein and polynucleotide, are
      extremely important biomacromoleules which play important roles in the growth and
      development of living organism. Polysaccharide is important component of higher
      plants, membrane of the animal cell and the cell wall of microbes. It is also
      closely related to the physiological functions. Recently, increasing attention
      has been paid on polysaccharides as an important class of bioactive natural
      products. Numerous researches have demonstrated the bioactivities of natural
      polysaccharides, which lead to the application of polysaccharides in the
      treatment of disease. In this paper, the various aspects of the investigation
      results of the bioactivities of polysaccharides were summarized, including its
      diversity pharmacological applications, such as immunoregulatory, anti-tumor,
      anti-virus, antioxidation, and hypoglycemic activity, and their application of
      polysaccharides in the treatment of disease are also discussed. We hope this
      review can offer some theoretical basis and inspiration for the mechanism study
      of the bioactivity of polysaccharides.

PMID- 29352897
TI  - Cost-utility of quadrivalent versus trivalent influenza vaccine in Brazil -
      comparison of outcomes from different static model types.
AB  - BACKGROUND: Influenza burden in Brazil is considerable with 4.2-6.4 million cases
      in 2008 and influenza-like-illness responsible for 16.9% of hospitalizations.
      Cost-effectiveness of influenza vaccination may be assessed by different types of
      models, with limitations due to data availability, assumptions, and modelling
      approach. OBJECTIVE: To understand the impact of model complexity, the cost
      utility of quadrivalent versus trivalent influenza vaccines in Brazil was
      estimated using three distinct models: a 1-year decision tree population model
      with three age groups (FLOU); a more detailed 1-year population model with five
      age groups (FLORA); and a more complex lifetime multi-cohort Markov model with
      nine age groups (FLORENCE). METHODS: Analysis 1 (impact of model structure)
      compared each model using the same data inputs (i.e., best available data for
      FLOU). Analysis 2 (impact of increasing granularity) compared each model
      populated with the best available data for that model. RESULTS: Using the best
      data for each model, the discounted cost-utility ratio of quadrivalent versus
      trivalent influenza vaccine was R$20,428 with FLOU, R$22,768 with FLORA (versus
      R$20,428 in Analysis 1), and, R$19,257 with FLORENCE (versus R$22,490 in Analysis
      1) using a lifetime horizon. Conceptual differences between FLORA and FLORENCE
      meant the same assumption regarding increased all-cause mortality in at-risk
      individuals had an opposite effect on the incremental cost-effectiveness ratio in
      Analysis 2 versus 1, and a proportionally higher number of vaccinated elderly in
      FLORENCE reduced this ratio in Analysis 2. DISCUSSION: FLOU provided adequate
      cost-effectiveness estimates with data in broad age groups. FLORA increased
      insights (e.g., in healthy versus at-risk, paediatric, respiratory/non
      respiratory complications). FLORENCE provided greater insights and precision
      (e.g., in elderly, costs and complications, lifetime cost-effectiveness).
      CONCLUSION: All three models predicted a cost per quality-adjusted life year
      gained for quadrivalent versus trivalent influenza vaccine in the range of
      R$19,257 (FLORENCE) to R$22,768 (FLORA) with the best available data in Brazil
      (Appendix A).

PMID- 29352898
TI  - Traffic University: How Small Changes in Lifestyle Can Change Your Life.

PMID- 29352899
TI  - Sodium alginate adhesives as binders in wood fibers/textile waste fibers
      biocomposites for building insulation.
AB  - Alginate derived from seaweed is a natural polysaccharide able to form stable gel
      through carbohydrate functional groups largely used in the food and
      pharmaceutical industry. This article deals with the use of sodium alginate as an
      adhesive binder for wood fibres/textile waste fibres biocomposites. Several
      aldehyde-based crosslinking agents (glyoxal, glutaraldehyde) were compared for
      various wood/textile waste ratios (100/0, 50/50, 60/40, 70/30 and 0/100 in
      weight). The fully biomass derived composites whose properties are herewith
      described satisfy most of the appropriate requirements for building materials.
      They are insulating with a thermal conductivity in the range 0.078-0.089 W/m/K
      for an average density in the range 308-333 kg/m3 according to the biocomposite
      considered. They are semi-rigid with a maximal mechanical strength of 0.84 MPa
      under bending and 0.44 MPa under compression for 60/40 w/w wood/textile waste
      biocomposites with a glutaraldehyde crosslinking agent.

PMID- 29352900
TI  - Evaluation of nisin-loaded chitosan-monomethyl fumaric acid nanoparticles as a
      direct food additive.
AB  - Nisin-loaded chitosan-monomethyl fumaric acid (CM-N) nanoparticles were evaluated
      as a novel, direct food additive. Chitosan (CS) was modified with monomethyl
      fumaric acid (MFA) in the presence of 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide (EDC). CS-loaded nisin (CS-N) and CM-N nanoparticles were produced
      through ionic interactions between the positive amino group of CS and CS-MFA and
      negative tripolyphosphate ions. The resultant materials were characterized by
      TNBS assay, X-ray diffraction, Fourier-transform infrared spectroscopy, scanning
      electron microscopy, thermogravimetric analysis, and zeta potential analysis. CS
      MFA was successfully synthesized with 8.38 +/- 0.02% substitution of the amino
      groups, as confirmed by TNBS assay. The percentage yield of CS-N and CM-N
      nanoparticles was 81.64 and 76.83% and nisin encapsulation efficiency was 71.48
      +/- 0.48 and 60.32 +/- 0.63%, respectively. The average particle size of CS-N and
      CM-N nanoparticles was 134.3 and 207.9 nm, while the zeta potential of CS-N and
      CM-N nanoparticles was +39.4 mV and +31.5 mV, respectively. Upon antibacterial
      activity against foodborne pathogens, CM-N significantly reduced bacterial counts
      compared to the other tested samples in orange juice after 48 h of incubation.
      Based on the preliminarily results, CM-N nanoparticles have shown impressive
      properties and can be used in the food industry as carriers and direct
      antimicrobial agents.

PMID- 29352901
TI  - Synthesis and characterization of carboxymethylcellulose grafted with
      thermoresponsive side chains of high LCST: The high temperature and high salinity
      self-assembly dependence.
AB  - Graft copolymers based on carboxymethylcellulose (CMC) and thermosensitive
      polyetheramines (ethylene oxide/propylene oxide = 33/10 and 1/9) were prepared in
      water, at room temperature, by using a carbodiimide and N-hydroxysuccinimide as
      activators. SLS was applied to obtain Mw, A2 and Rg of CMC and its derivatives.
      Amide linkages were evidenced by FTIR and grafting percentage was determined by
      1H NMR. TGA demonstrated that copolymers were thermally more stable than their
      precursors. DLS, UV-vis and rheological measurements revealed that properties
      were salt- and thermo-responsive and linked to the polysaccharide/polyetheramine
      ratio and the hydrophobicity of the graft. None of the copolymers showed cloud
      point temperature (Tcp) in water, but they turned turbid in saline media when
      heated. Copolymers exhibited thermothickening behaviour at 60  degrees C (>Tcp)
      in saline media. Below their Tcp, they showed the ability of keeping constant
      viscosity or even slight increase it, which was interpreted in terms of
      intermolecular hydrophobic associations.

PMID- 29352902
TI  - Thermoresponsive behavior of sodium alginate grafted with poly(N
      isopropylacrylamide) in aqueous media.
AB  - Thermoresponsive graft copolymers were synthesized. Thermally induced properties
      were introduced by grafting poly (N-isopropylacrylamide) (PNIPAM) side chains
      onto a sodium alginate backbone. The resulting graft copolymers cover a broad
      range in PNIPAM composition and molecular weight. Remarkable thermothickening
      behavior in water and 0.1 M NaCl is observed by viscometry when the temperature,
      concentration, weight ratio of PNIPAM side chains to backbone, and PNIPAM
      molecular weight are higher than certain critical values. This behavior is
      reversible and could have applications in oil rigs and drug delivery systems.

PMID- 29352903
TI  - Isolation, fine structure and morphology studies of galactomannan from endosperm
      of Gleditsia japonica var. delavayi.
AB  - The water-soluble polysaccharides extracted from endosperm of Gleditsia japonica
      var. delavayi seeds (EGSP) were identified as galactomannan having the M/G ratio
      of 2.54-2.66 and a weight average molecular weight (Mw) of 1913 kDa. The
      molecular structure of EGSP was determined by periodate oxidation, Smith
      degradation, methylation, FTIR and NMR spectroscopy. The main chain is composed
      of beta-1,4-d-mannopyranose and the branches composed of single alpha-1-d
      galactopyranose. We had also established a model to speculate the fine structure
      of galactomannan molecules and given preliminary results. The I2-KI test
      indicated that there were many branches on the EGSP backbone and no starch in
      EGSP. The CD spectra and Congo red test showed EGSP was random coil conformations
      in solution and could form a small quantity of helical conformation under
      alkaline conditions. The microstructure of morphology was observed by OM, SEM and
      AFM. The results showed that the fibers composed of multiple microfibers formed a
      network construction by entangling with each other.

PMID- 29352904
TI  - Structural properties and in vitro digestibility of edible and pH-sensitive films
      made from guinea arrowroot starch and wastes from wine manufacture.
AB  - A non-conventional starch obtained from guinea arrowroot tubers (Calathea
      allouia) grown in the Amazon was used as a polymeric matrix for the development
      of edible films. The films were manufactured by blending/thermo molding and
      plasticized with glycerol. Agro-industrial wastes from wine manufacture (grape
      waste flour and grape waste extract) were used as natural fillers of the
      thermoplastic starch (TPS) matrices. The results showed that the natural fillers
      caused cross-linking in the TPS matrix. This led to the production of films with
      higher resistant starch (RS) content, especially RS type 4 (RS4), although the
      DSC results showed that the films developed also contained RS type 3 (RS3). As
      expected, the presence of RS reduced the in vitro digestibility rate. Films made
      with the natural fillers were also less hydrophilic, had a greater thermal
      resistance, and tended towards ductile mechanical behavior. Finally, the edible
      film containing grape waste flour as a natural filler proved to be pH-sensitive,
      although this material disintegrated under alkaline conditions.

PMID- 29352905
TI  - Glucose-sensitive polyelectrolyte microcapsules based on (alginate/chitosan)
      pair.
AB  - Novel chemical stimulus-responsive multilayer assemblies have been elaborated
      through the layer-by-layer deposition of oppositely charged polysaccharides on
      either flat or spherical surfaces. Concentration-dependent glucose responsiveness
      was obtained through chemical modification of alginate, selected as polyanion,
      with phenylboronic acid moieties. QCM measurements showed that the alginate
      derivate still self-assembles though electrostatically-driven interactions with
      chitosan at pH 4, and that the polysaccharides multilayer assemblies, as obtained
      after crosslinking, exhibit improved stability versus pH (in the range 4-9) as
      well as swelling ability in the presence of glucose-containing solution.
      Glutaraldehyde-mediated crosslinking was achieved through reaction with free
      primary amines of chitosan. This approach was further extended to the preparation
      of smart capsules using CaCO3 microparticles as dissolvable core templates.
      Success of the LbL deposition process, stability (pH range 4-9) of the multilayer
      assemblies and glucose-induced swelling were fully confirmed for the
      microcapsules. One of the major result of this study is that crosslinking
      prevents total dissolution of the capsules and enables modulating the
      permeability of the polysaccharide shell yielding controlled release on in
      capsule entrapped low molecular weight molecules.

PMID- 29352906
TI  - Preparation of composite hydroxybutyl chitosan sponge and its role in promoting
      wound healing.
AB  - In this work, a composite sponge was produced by physically mixing hydroxybutyl
      chitosan with chitosan to form a porous spongy material through vacuum freeze
      drying. Hydrophilic and macroporous composite hydroxybutyl chitosan sponge was
      developed via the incorporation of chitosan into hydroxybutyl chitosan. The
      composite sponge showed higher porosity (about 85%), greater water absorption
      (about 25 times), better softness and lower blood-clotting index (BCI) than those
      of chitosan sponge and hydroxybutyl chitosan sponge. The composite sponge with
      good hydrophilic could absorb the moisture in the blood to increase blood
      concentration and viscosity, and become a semi-swelling viscous colloid to clog
      the capillaries. Cytocompatibility tests with L929 cells and HUVEC cells
      demonstrated that composite sponge were no cytotoxicity, and could promote the
      growth of fibroblasts. It made up for the shortcomings of hydroxybutyl chitosan
      with unfavorable antibacterial effect to achieve a higher level of antibacterial
      (>99.99% reduction). Eventually, the vivo evaluations in Sprague-Dawley rats
      revealed that epithelial cells attached to the composite sponge and penetrated
      into the interior, in addition to this, it was also proved that the composite
      sponge (HC-1) had a better ability to promote wound healing and helped for faster
      formation of skin glands and re-epithelialization. The obtained data encourage
      the use of this composite sponge for wound dressings.

PMID- 29352907
TI  - Preparation and characterization of microcrystalline cellulose (MCC) from tea
      waste.
AB  - Microcrystalline cellulose (MCC) was prepared from Oolong tea waste by acid
      hydrolysis in the present study. Based on the single factor experiment results,
      the hydrolysis conditions were optimized by an orthogonal L9(3)4 experiment.
      Results showed that the degree of polymerization (DP) and yield of MCC were
      strongly influenced by the time and temperature of hydrolysis, the concentration
      of HCl and the ratio of acid to material. Under optimal conditions (acid to
      materials ratio 1:20, HCl concentration 1.5 mol/L, 65  degrees C, 90 min), the
      yield and DP of the tea waste MCC were 86.7% and 145, respectively. Fourier
      transform-infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) analysis
      indicated that tea waste MCC had cellulosic structure and was cellulose I type.
      Scanning electron microscopy (SEM) showed that MCC had shorter fibers with some
      holes on the rough surface. The MCC prepared from tea waste had good thermal
      stability.

PMID- 29352908
TI  - Preparation of starch nanocrystals through enzymatic pretreatment from waxy
      potato starch.
AB  - A comparative experiment about the production of starch nanocrystals (SNCs)
      with/without glucoamylase enzymatic pretreatment by sulfate acid hydrolysis from
      waxy potato starch (WPS) was employed in the present study. The research focused
      on the enhancement of the preparation efficiency while improving the dispersion
      of SNCs at the same time. The enzymatic pretreatment resulted in the decrease of
      acid hydrolysis duration. The minimum size and best dispersibility of
      nanocrystals was obtained after 5 days of hydrolysis. X-ray diffraction confirmed
      the increase of crystallinity (from 33% to 50.8%) and the polymorphic transitions
      (B-A) for nanocrystals harvested at day 5. The structure of nanocrystals was
      characterized by FT-IR, which suggested the presence of sulfate ester on the
      surface of SNCs. Zeta potential and size distribution revealed the prominent
      stability and dispersibility of nanocrystals at pH 7.0. SEM and TEM revealed that
      SNCs had square shapes with particle sizes ranging from 50 to 100 nm.

PMID- 29352909
TI  - A review of polysaccharides from Schisandra chinensis and Schisandra
      sphenanthera: Properties, functions and applications.
AB  - Schisandra is an herbal plant resource with dual functions in medicine and food
      since ancient times. It has a variety of healthcare and therapeutic effects.
      Schisandra chinensis (Turcz.) Baill and Schisandra sphenanthera Rehd. et Wits are
      two of the most commonly used Schisandra. Traditional Chinese medicine experience
      has shown that water-soluble polysaccharide from Schisandra may be one of its
      main components with pharmacological effects. Progress in the industrial
      production and extraction process of plant polysaccharides, especially Chinese
      medicine polysaccharides in the past three decades, have led to many new
      discoveries about Schisandra polysaccharides in the fields of purification and
      identification. Their health benefits and pharmacological value have increased
      the interest of the public and academia. This review summarizes the
      physicochemical properties and biological functions of polysaccharides from two
      Schisandra fruits, and the application prospects of these bioactive
      macromolecules in future daily life and medicine.

PMID- 29352910
TI  - A novel photocleavable heparin derivative with light controllable anticoagulant
      activity.
AB  - Heparin (HP) has enormous potential for clinical medication applications owing to
      its anticoagulant activity. However, the strong anticoagulant capacity of HP also
      leads to some side effects. Herein, a photocaged derivative (HP-DMNB) of HP was
      synthesized for light control of its anticoagulant activity. The synthesized HP
      DMNB was characterized by NMR and FTIR analysis, which confirmed the successful
      modification of HP with the photocleavable 4,5-dimethoxyl-2-nitrobenzyl (DMNB)
      groups. After the modification, the molecular weight of HP-DMNB (DS = 0.34%)
      changed from 61 to 71 kDa. Anticoagulant activity analysis showed that HP-DMNB
      had a reduced anticoagulant capacity compared with commercial HP, while its
      anticoagulant activity will regain after releasing the free carboxyl groups of HP
      under UV light. In addition, HP-DMNB and its UV irradiated products were observed
      to possess good biocompatibility through the MTT assays and live-dead assays with
      HaCaT cells, which may have impacts on the clinical medication applications of
      HP.

PMID- 29352911
TI  - HPMCAS as an effective precipitation inhibitor in amorphous solid dispersions of
      the poorly soluble drug candesartan cilexetil.
AB  - Among the strategies to improve the biopharmaceutic properties of poorly soluble
      drugs, Supersaturating Drug Delivery Systems like polymer-based amorphous solid
      dispersions (SD) have been successfully applied. The screening of appropriate
      polymeric carriers to compose SD is a crucial point on their development. In this
      study, hydroxypropylmethylcellulose (HPMC), hydroxypropylmethylcellulose acetate
      succinate (HPMCAS) types L, M and H and polyvinyl caprolactam-polyvinyl acetate
      polyethylene glycol graft copolymer (SOL) were evaluated by in vitro
      supersaturation studies regarding their anti-precipitant ability on the poorly
      soluble drug candesartan cilexetil (CC) under two different media, including
      biorelevant conditions. According to the results, HPMCAS M was considered the
      best carrier to develop SD containing CC among all the polymers tested, due to
      its good anti-precipitant performance in both media. In addition, the medium used
      in the in vitro supersaturation studies played an important role on the results,
      and its selection should be carefully done.

PMID- 29352912
TI  - Synthesis of a poly(ester) dendritic beta-cyclodextrin derivative by "click"
      chemistry: Combining the best of two worlds for complexation enhancement.
AB  - In spite of the progress in the cyclodextrins chemistry, the synthesis of
      monodisperse derivatives with a defined degree of substitution is still a
      challenge. In this work we present a novel dendritic material produced by
      combining betaCD and second generation poly(ester) dendrons. The selective
      attachment of dendrons in the seven positions of the betaCD-primary face was
      performed through a CuAAC click reaction, which along with a very simple work-up,
      allowed obtaining the monodisperse material in very high yields. The product
      showed a great aqueous solubility and an in vitro non-toxic profile. The enhanced
      complexation potential of the product was evidenced through the formation of an
      inclusion complex with albendazole, which presented a Kc = 29636.17 M-1. In this
      system, albendazole was 45 times more water-soluble in comparison to the complex
      albendazole-native betaCD. All these features make the dendritic material very
      attractive for further applications in the formulation and drug delivery fields.

PMID- 29352913
TI  - Response surface methodology for optimisation of edible coatings based on dextran
      from Leuconostoc mesenteroides T3.
AB  - The aim of this study was to develop dextran-based edible films plasticized by
      sorbitol. In order to optimise the film-forming formulation, response surface
      methodology was used. The influence of dextran and sorbitol concentration on the
      mechanical and water vapour barrier properties of obtained films was
      investigated. The results showed that both parameters exhibited significant
      effect on the water vapour permeability of a film. Both dextran and sorbitol
      concentration had significant influence on tensile strength and elongation at
      break, whereas only sorbitol concentration had significant effect on Young's
      modulus. After optimisation by desirability approach, it was found that a film
      made of 3.40 wt% of dextran and 20.43 wt% of sorbitol showed the lowest water
      vapour permeability and the highest tensile strength and elasticity.

PMID- 29352914
TI  - Silica in situ enhanced PVA/chitosan biodegradable films for food packages.
AB  - Non-degradable plastic food packages threaten the security of environment. The
      cost-effective and biodegradable polymer films with good mechanical properties
      and low permeability are very important for food packages. Among of biodegradable
      polymers, PVA/chitosan (CS) biodegradable films have attracted considerable
      attention because of feasible film forming ability. However, PVA/CS biodegradable
      films suffered from poor mechanical properties. To improve mechanical properties
      of PVA/CS biodegradable films, we developed SiO2in situ to enhance PVA/CS
      biodegradable films via hydrolysis of sodium metasilicate in presence of PVA and
      chitosan solution. The tensile strength of PVA/CS biodegradable films was
      improved 45% when 0.6 wt.% SiO2 was incorporated into the films. Weight loss of
      PVA/CS biodegradable films was 60% after 30 days in the soil. The permeability of
      oxygen and moisture of PVA/CS biodegradable films was reduced by 25.6% and 10.2%,
      respectively. SiO2in situ enhanced PVA/CS biodegradable films possessed not only
      excellent mechanical properties, but also barrier of oxygen and water for food
      packages to extend the perseveration time.

PMID- 29352915
TI  - Silver(I) dithiocarbamate on modified magnetic cellulose: Synthesis, density
      functional theory study and application.
AB  - A magnetically retrievable catalytic system involving Ag(I) dithiocarbamate
      supported on functionalized cellulose was prepared. The structure of this hybrid
      nano-composite was characterized by various techniques. In addition, to describe
      the metal-ligand interactions present in the nano-composite, covalent and
      electrostatic interactions, density functional theory model and quantum theory of
      atoms in molecule method were employed. The resultant nano-composite exhibits
      remarkable catalytic efficacy in the synthesis of 2-amino-6-(2-oxo-2H-chromen-3
      yl)-4-phenylnicotinonitriles from the reaction of 3-acetylcoumarin, aromatic
      aldehydes, and malononitrile. Its recoverability and reusability for this
      catalyst was examined in several runs, which showed no appreciable loss after
      five runs. The facile accessibility to the starting materials, and conducting the
      reactions in the eco-friendly and cost-effective conditions are the other merits
      of such new catalyst. Ambient reaction conditions, wide substrate scope, and
      facile accessibility to the starting materials, are some of the other outstanding
      features of this protocol that make it economic and sustainable.

PMID- 29352917
TI  - Chitooligosaccharides and their biological activities: A comprehensive review.
AB  - Chitin is the most abundant natural polysaccharide and chitosan is its most
      important derivative. Regardless of having various bioactivities, the water
      insolubilities of chitin and chitosan limit their applications in many
      industries. The physical, chemical or enzymatic depolymerization of chitin and
      chitosan deliver chitooligosaccharides (COS): water-soluble and low molecular
      weight derivatives, superior to the parent polymers in multiple aspects. COS
      exhibit an enormously wide range of biological activities and a remarkable
      potential to be applied in various industries. This review has fully addressed
      the latest research on the biological activities of COS and the molecular
      mechanism behind these activities in a correlation with their physicochemical
      properties. Furthermore, an attempt has been made to report the commercially
      available COS products. The bioactivities discussed here may offer new
      understanding of the applications of COS in numerous sectors.

PMID- 29352916
TI  - Effect of Punica granatum peel extracts on antimicrobial properties in Walnut
      shell cellulose reinforced Bio-thermoplastic starch films from cashew nut shells.
AB  - The main aim of the present study is to extract and characterize cashew nut shell
      (CNS) starch and walnut shell cellulose (WNC) for development of cellulose
      reinforced starch films. Moreover, the extraction and characterization of
      pomegranate peel extract, for incorporation with CNS-WNC films, was investigated.
      CNS starch was examined to be a moderate amylose starch with 26.32 +/- 0.43%
      amylose content. Thermal degradation temperature of CNS starch was found to be
      310  degrees C. Walnut shell cellulose was found to have high crystallinity index
      of 72%, with two thermal degradation temperatures of 319  degrees C and 461 
      degrees C. 2% WN cellulose reinforced CNS starch films were examined to have good
      oxygen transfer rate, mechanical and physical properties. Thermal degradation
      temperature of CNS-WNC starch films were found to be at the range of 298-302 
      degrees C. Surface roughness of CNS-WNC starch films were found to be increasing
      with increase in concentration of cellulose in films. Hydroxymethylfurfurole,
      Benzene, 2-methoxy-1,3,4-trimethyl and 1,2,3-Propanetriol, 1-acetate were found
      to be major active compounds present in hydrophilic extracts of Punica granatum
      peels. 2% WN cellulose reinforced starch films infused with hydrophilic active
      compounds of pomegranate peel was examined to be having good active package
      properties.

PMID- 29352918
TI  - Structural characteristics and anticancer activity in vitro of fucoidan from
      brown alga Padina boryana.
AB  - The sulfated and acetylated fucoidan fraction, containing fucose, galactose,
      mannose, glucose and uronic acid residues, was isolated from the brown alga
      Padina boryana. The structure of galactofucan part was studied after different
      modifications by NMR spectroscopy and mass spectrometry. It was shown that
      galactofucan contained the main chain of alternating 1,4-linked alpha-l
      fucopyranose and 1,3-linked beta-d-Galactopyranose. Single fucose residues were
      found as branches at C4 of galactose residues. Also, fucoidan contained 1,3- or
      1,4-linked Fuc-Fuc and Gal-Gal fragments. The sulfate groups occupied positions
      C2, C3 and C4 of both fucose and galactose residues, which was shown by tandem
      mass spectrometry of fragments, labeled with heavy-oxygen. The anticancer effect
      of native and modified fucoidan fractions was studied in vitro on the colorectal
      carcinoma cells DLD-1 and HCT-116. All fucoidans had no cytotoxicity under 400
      MUg/mL and inhibited colony formation of cancer cells at concentration of 200
      MUg/mL.

PMID- 29352919
TI  - Comprehensive analysis of glycosaminoglycans from the edible shellfish.
AB  - We have previously reported that the keratan sulfate (KS) disaccharide was
      branched to the C-3 position of glucuronate in chondroitin sulfate (CS)-E derived
      from the Mactra chinensis. We carried out the comprehensive disaccharide analysis
      of GAGs from 10 shellfish, Ruditapes philippinarum, Scapharca broughtonii,
      Mizuhopecten yessoensis, Turbo cornutus, Crassostrea nippona, Corbicula japonica,
      Mytilus galloprovincialis, Neptunea intersculpta, Pseudocardium sachalinense and
      Crassostrea gigas, to better understand the glycan structures in marine
      organisms. The contents of CS, heparan sulfate and hyaluronic acid and their
      compositions depend on the species of shellfish. Interestingly, a peak
      corresponding to a pentasaccharide containing KS disaccharide was observed when
      GAGs from T. cornutus was treated with chondroitinase (Chase) ACII but not Chase
      ABC. In addition, unidentified peaks were also observed when CS derived from R.
      philippinarum, S. broughtonii were treated with Chase ACII. These results suggest
      the presence of additional unidentified structure of CS in these shellfish.

PMID- 29352920
TI  - Biomass-based magnetic fluorescent nanoparticles: One-step scalable synthesis,
      application as drug carriers and mechanism study.
AB  - A biomass-based magnetic fluorescent nanoparticle (MFNPs) was successively in
      situ synthesized via a one-step high-gravity approach, which constructed by a
      magnetic core of Fe3O4 nanoparticles, the fluorescent marker of carbon dots
      (CDs), and shells of chitosan (CS). The obtained MFNPs had a 10 nm average
      diameter and narrow particle size distribution, low cytotoxicity, superior
      fluorescent emission and superparamagnetic properties. The encapsulating and
      release 5-fluorouracil experiments confirmed that the introduction of CS/CDs
      effectively improved the drug loading capacity. Mechanism and kinetic studies
      proved that: (i) the monolayer adsorption was the main sorption mode under the
      studied conditions; (ii) the whole adsorption process was controlled by intra
      liquid diffusion mass transfer and governed by chemisorption; and (iii) the
      release process was controlled by Fickian diffusion. These results demonstrated
      this method to one-step continuously produce MFNPs and the construction of non
      toxic nanostructure possessed great superiority in currently Nano-delivery
      systems, which would show high application value in targeted drug delivery,
      magnetic fluid hyperthermia treatment, magnetic resonance imaging (MRI), in vitro
      testing and relative research.

PMID- 29352921
TI  - Anti-osteoporosis activity of a novel Achyranthes bidentata polysaccharide via
      stimulating bone formation.
AB  - Achyranthes bidentata is an important Traditional Chinese Medicine for the
      treatment of osteoporosis. In this study, A. bidentata polysaccharide (ABPB),
      which was extracted with alkali from the root of A. bidentata at room
      temperature, significantly increased the bone mineral density, bone mineral
      content, trabecular thickness, trabecular number and biomechanical properties of
      ovariectomized (OVX) rats, indicating that ABPB had prominent curative effects on
      osteoporosis in OVX rats. A novel polysaccharide (ABPB-3) was purified from ABPB,
      and its structure was characterized as a repeating unit consisting of ->4)-alpha
      d-GalpA-(1->, ->2,4)-alpha-l-Rhap-(1->, ->5)-alpha-l-Araf-(1->, ->2,3,5)-alpha-l
      Araf-(1->, ->3)-beta-d-Galp-(1->, ->3,4,6)-beta-d-Galp-(1->, terminated with
      alpha-l-Araf, alpha-l-Rhap and beta-d-Galp. Up to now, there were no literature
      reports relevant to the structure of ABPB-3. In the zebrafish model of
      glucocorticoid-induced osteoporosis (GIOP), ABPB-3 significantly increased the
      relative fluorescence intensity of the skull bone mass in a concentration
      dependent manner, indicating that it stimulated bone formation activity. Thus,
      ABPB and ABPB-3 have the potential to be used for the anti-osteoporosis medicine.

PMID- 29352922
TI  - Cellulose nanofiber-embedded sulfonated poly (ether sulfone) membranes for proton
      exchange membrane fuel cells.
AB  - Cellulose nanofibers were embedded into sulfonated poly (ether sulfone) matrix to
      heighten the water retention and proton conductivity of proton exchange membranes
      (PEMs). Cellulose nanofibers were obtained by hydrolyzing cellulose acetate
      nanofibers, which were prepared via electrostatic-induction-assisted solution
      blow spinning. Morphology, thermal stability, and mechanical properties of the
      PEMs were investigated. The results showed that proton conductivity, water
      uptake, and methanol permeability of the composite membranes were improved.
      Hydrophilicity of the composite membranes was gradually improved with the
      addition of nanofibers. When the content of nanofibers was 5 wt%, the highest
      proton conductivity was 0.13 S/cm (80  degrees C, 100% RH). Therefore, the
      cellulose nanofiber could be used as support materials to enhance the performance
      of proton exchange membranes, the composite membranes have potential application
      in Direct methanol fuel cells (DMFCs).

PMID- 29352923
TI  - Fabrication of cellulose/graphene paper as a stable-cycling anode materials
      without collector.
AB  - Flexible and foldable devices attract substantial attention in low-cost
      electronics. Among the flexible substrate materials, paper has several attractive
      advantages. In our study, we fabricate cellulose/graphene paper by wet end
      formation (papermaking). The cationic polyacrylamide remarkably improve the
      retention ratio of graphene of cellulose/graphene slurry. Besides,
      cellulose/graphene paper exhibits well mechanical properties such as its
      flexibility and folding endurance. And we replace copper foil collector with
      cellulose/graphene paper in lithium-ion batteries without collector, and
      investigate its electrochemical properties. The obtained results show that
      cellulose/graphene paper presents excellent charge-discharge stability after
      1600th cycles as the anode of lithium-ion batteries. These advantages highlight
      the potential applications of cellulose/graphene paper as anode materials for
      lithium-ion batteries.

PMID- 29352924
TI  - Producing nanofibres from carrots with a chemical-free process.
AB  - The production of nanofibres (NF) from fresh carrots residue was investigated
      with a mechanical process without using any pulping or bleaching chemicals.
      Refining with a PFI mill followed by mechanical fibrillation with a homogenizer
      was used to produce fine NF. Blanching with hot water was carried out to leach
      the extractives from carrot fibres prior to refining. The energy required to
      prepare carrot pulp is one order of magnitude lower than for wood pulp and the
      fibrillation of nanofibres from carrot residue is four times lower in energy than
      using wood pulp as feedstock. The average diameter and length of carrot NF are 18
      nm and 5.1 MUm, respectively. The chemical composition of the manufactured
      nanofibers, as measured by HPLC, was 53% glucose and 47% xylose. Translucent and
      strong flexible films were prepared from the carrot NF using a filtration based
      papermaking process. The strength and water vapor permeability of these carrot NF
      paper like composites are similar to those derived from wood-fibre of comparable
      dimensions.

PMID- 29352925
TI  - Influence of hydrothermal treatment on the structural modification of spent grain
      specific carbohydrates and the formation of degradation products using model
      compounds.
AB  - Brewer's spent grain (BSG) constitutes various valuable carbohydrates that may
      contribute to a healthy diet. These components may be obtained from BSG via
      hydrothermal treatment (HT), a procedure for dissolving water-inextricable
      carbohydrates. The objective of this study was to investigate HT as an
      environmentally friendly technology for extracting high-molecular-weight fiber
      with proven beneficial effects on human health. Cellulose, beta-glucan, and
      arabinoxylan (AX) served as model substances and were subjected to auto
      hydrolysis at different temperatures and reaction times. The results were
      evaluated in terms of structural and chemical characteristics. When the treatment
      temperature was increased, the original weight-average molar mass of AX (370 kDa)
      and beta-glucan (248 kDa) decreased gradually (<10 kDa), and the molar mass
      distribution narrowed. Further investigations focused on the heat-induced
      formation and elimination of monosaccharides and undesirable by-products. The
      concentrations of by-products were successfully described by kinetic models that
      can be used to optimize the hydrolysis process.

PMID- 29352927
TI  - Self-assembly and rheological behaviors of intermacromolecular complexes
      consisting of oppositely charged fluorinated guar gums.
AB  - We synthesized fluorinated cationic/anionic guar gums (FCGG and FAGG) and
      characterized these species using Fourier transform infrared spectroscopy and 1H
      nuclear magnetic resonance spectroscopy. The degree of fluorine substitution of
      FCGG (0.26%) and FAGG (0.21%) was calculated by elemental analysis. In addition,
      we explored the self-assembly and rheological behaviors of FCGG-FAGG complexes by
      viscometry, scanning electron microscopy, light scattering, fluorescence
      spectroscopy, and rheometry. The maximum viscosity and molecular weights were
      observed with a FAGG:FCGG mass ratio of 7.0:3.0, denoted by COMP. Moreover, FAGG
      FCGG interactions in COMP led to the lowest shape factor and critical associating
      concentration. Additionally, the relaxation time and crossover modulus of COMP
      (6.65 s and 0.90 Pa, respectively) were remarkably higher than those of FCGG and
      FAGG alone. Finally, viscoelastic hysteresis loops emerged for FAGG and COMP. The
      results suggested that the self-assembly behaviors of FAGG-FCGG were influenced
      by both ionic and fluorinated groups.

PMID- 29352926
TI  - A novel microporous oxidized bacterial cellulose/arginine composite and its
      effect on behavior of fibroblast/endothelial cell.
AB  - The bacterial cellulose (BC) has been reported widely. Although there are many
      methods to modify BC, such as the oxidized BC, which is biodegradable and can be
      used as wound dressing. However, the nanostructure of BC makes it difficult to be
      oxidized. Importantly, high oxidation degree makes the content of aldehyde high,
      which make the cell biocompatibility poor. Herein, we fabricated a novel bio
      composite based on microporous oxidized BC (MOBC) and in-situ grafted with Arg.
      The micropores can increase the contact area between BC and oxidizing agent and
      the reaction between MOBC and Arg, which will enhance the biocompatibility. The
      roughness and surface energy of MOBC/68.68%Arg are 1.5 and 1.16 times than that
      of BC respectively. We applied a microfluidic chip to evaluate the cell
      migration. Comparing with BC, MOBC/Arg promoted proliferation, migration and
      expression of Collagen-I of fibroblasts and endothelial cells. It prospects the
      MOBC/Arg can be used as wound dressing.

PMID- 29352928
TI  - Thermo-sensitive injectable glycol chitosan-based hydrogel for treatment of
      degenerative disc disease.
AB  - The use of injectable hydrogel formulations have been suggested as a promising
      strategy for the treatment of degenerative disc disease to both restore the
      biomechanical function and reduce low back pain. In this work, a new thermo
      sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced
      stability were developed with N-hexanoylation of glycol chitosan (GC) for
      treatment of degenerative disc disease, and their physico-chemical and biological
      properties were evaluated. The sol-gel transition temperature of the hydrogels
      was controlled in a range of 23-56  degrees S, depending on the degree of
      hexanoylation and the polymer concentration. In vitro and in vivo tests showed no
      cytotoxicity and no adverse effects in a rat model. The hydrogel filling of the
      defective IVD site in an ex vivo porcine model maintained its stability for
      longer than 28 days. These results suggest that the hydrogel can be used as an
      alternative material for treatment of disc herniation.

PMID- 29352929
TI  - Structural characterization, antioxidant and hepatoprotective activities of
      polysaccharides from Sophorae tonkinensis Radix.
AB  - In current study we present two polysaccharides, STRP1 and STRP2, purified from
      Sophorae tonkinensis Radix via column chromatography. Structural analyses
      indicated that STRP1 and STRP2 were consisted of mannose, rhamnose, glucuronic
      acid, glucose, galactose and arabinose in a similar molar ratio with main
      backbones of (1 -> 3)-linked-alpha-d-Gal and (1 -> 4)-linked-alpha-d-Glc, while
      average molecular weights were 1.30 * 104 and 1.98 * 105 Da, respectively. We
      observed a strong chelating ability on ferrous ions; substantial radical
      scavenging activities on DPPH, hydroxyl and superoxide anion radicals in vitro;
      and significant attenuation on acetaminophen-induced hepatic oxidative damage in
      mice for STRP1 and STRP2. The promising data on these polysaccharides showcase
      the need to further develop novel natural antioxidant and liver-protecting drugs.

PMID- 29352931
TI  - Effects of chitosan quaternary ammonium salt on the physicochemical properties of
      sodium carboxymethyl cellulose-based films.
AB  - The effects of N-(2-hydroxyl)-propyl-3-trimethylammonium chitosan chloride (HTCC)
      on the physicochemical properties of sodium carboxymethyl cellulose (CMC)-based
      films were investigated. The prepared HTCC/CMC film-forming solutions (FFSs) with
      varying mass ratios exhibited shear-thinning behavior and typical pseudo
      plasticity. The highest apparent viscosity and lowest crossover frequency was
      obtained for the HTCC/CMC FFS with a mass ratio of 10%, due to the formation of
      the strongest intermolecular interactions, which also led to the best mechanical
      properties. Furthermore, the effects of temperature and degree of substitution of
      HTCC on the composite film properties were also investigated. Structural property
      assessment by FTIR, SEM, and DSC showed a clear interaction between HTCC and CMC,
      leading to the formation of a new composite material with enhanced
      physicochemical properties. The data demonstrate the importance of HTCC in CMC
      based films for food and drug packaging.

PMID- 29352930
TI  - An efficient approach to prepare sulfated polysaccharide and evaluation of anti
      tumor activities in vitro.
AB  - Use of microwave radiation is one of the most potential techniques in
      polysaccharide derivatives synthesis due to its advantages such as higher yields,
      milder reaction conditions and shorter reaction times. This study was aimed at
      producing sulfated polysaccharides by microwave irradiation using polar reagents
      and solvent. Six sulfated Artemisia sphaerocephala polysaccharide derivatives
      (SPAS) were obtained by using chlorosulfuric acid/pyridine method in the reaction
      duration range of 15-300 min at a fixed microwave power of 100W. Synthesis of
      SPAS under microwave filed was highly effective and characterized by time saving
      and high degrees of substitution (DS). The chemical structure of SPAS was
      confirmed by FT-IR and 13C NMR that sulfation had occurred and the substitution
      position was mainly at C-6. Size-exclusion chromatograph combined with multi
      angle laser photometer (SEC-MALLS) data indicated that short reaction time
      minimized acid-catalyzed degradation of polysaccharide chains. AFM observation
      demonstrated that low-MW derivative exhibited aggregation of polysaccharide chain
      as irregular spherical lumps. In anti-tumor activity assays, sulfation of PAS
      significantly improved the capacity to inhibit tumor cells growth by arresting
      the cell cycle progress in specific phases. It could be concluded that MW and
      molecular mass distribution had much greater influence on anti-tumor activities
      of SPAS against human non-small cell lung cancer A549 cells, human hepatocellular
      carcinoma HepG2 cells and human cervical cancer Hela cells. Microwave-assisted
      synthesis might possess widespread application in preparation of new
      polysaccharide derivatives with rich variety of structural features and
      bioactivities.

PMID- 29352932
TI  - The effect of nanocrystalline cellulose on flow properties of fiber crop aqueous
      suspension.
AB  - Nanocrystalline cellulose (NCC) a nature-based material, has gained significant
      attentions for its unique properties. The present study aims to investigate the
      flow behavior of cellulosic suspension containing non-wood pulp fibers and NCC,
      by means of rheological and pressure drop measurements. The NCC sample was
      prepared by sulfuric acid hydrolysis from Acacia mangium fibers. The rheological
      properties of kenaf/NCC suspensions were studied using viscosity and yield stress
      measurements. The pressure drop properties of the suspension flow were studied
      with respect to variation in flow velocity (0.4 m/s-3.6 m/s) and the NCC
      concentration (70 mg/l and 150 mg/l). The pressure drop results showed that the
      pulp suspension containing 150 mg/l NCC had higher drag reduction than kenaf
      suspension alone. The present insights into the flow of pulp/NCC suspension
      provide a new data and promote the application of NCC in industries.

PMID- 29352933
TI  - Photopolymerized maleilated chitosan/thiol-terminated poly (vinyl alcohol)
      hydrogels as potential tissue engineering scaffolds.
AB  - Photocrosslinkable hydrogels composed of natural materials exhibit great
      application potential in tissue engineering scaffolds. However, weak formation
      and poor mechanical property can usually be a limitation. Herein, the photo
      clickable thiol-ene hydrogels based chitosan were synthesized using
      photopolymerization of maleic chitosan (MCS) and thiol-terminated poly (vinyl
      alcohol) (TPVA) in the presence of a biocompatible photoinitiator. Rheological
      property and absorbing behavior of the MCS/TPVA hydrogels could be tailored by
      varying the amount of TPVA in the feed. There was strong intermolecular hydrogen
      bonding between the molecules of MCS and TPVA. Notably, the MCS/TPVA hydrogel (MT
      3) exhibited rapid gelation behavior (<120 s), improved stiff (G' = ~5500 Pa) and
      compressive strength (0.285 +/- 0.014 MPa), which were important for hydrogel
      scaffolds, especially for injectable hydrogel scaffolds. Photocrosslinked
      MCS/TPVA hydrogels was cytocompatible and could promote the L929 cells attachment
      and proliferation, showing their potential as tissue engineering scaffolds.

PMID- 29352934
TI  - gamma-Cyclodextrin-phenylacetic acid mesh as a drug trap.
AB  - In this study, we developed a nanoporous biodegradable mesh, bioinspired by the
      spider web, which is prepared via electrospinning using gamma-cyclodextrin (gamma
      CD) conjugated with phenylacetic acid (PA), named gamma-CDP. The resulting gamma
      CDP has a microfibrous or microspherical shape and contains drug trap meshlike
      gamma-CD pores. These gamma-CDP micromeshes (microspheres or microfibers) enable
      efficient drug capture and drug transport into deep gamma-CDP nanocompartments or
      out of the gamma-CDP web, resulting in a driving domain for a 4-week drug
      release. When used to deliver chemotherapeutic agents to xenografted tumors, the
      gamma-CDP implants caused nearly complete tumor regression for 4 weeks after
      single administration. This strategy of a drug trap biodegradable mesh (with low
      density) will make drug containers uniquely attractive for the development of
      therapeutic implants and functional biomedical devices.

PMID- 29352935
TI  - Development of pH-responsive chitosan-based hydrogel modified with bone ash for
      controlled release of amoxicillin.
AB  - In present study, bone ash-reinforced chitosan-based hydrogels were obtained by
      encapsulation of bone ash into the hydrogel structure which was fabricated by
      photopolymerization of chitosan-grafted-glycidyl methacrylate (CTS-g-GMA) and
      poly(ethylene glycol)diacrylate (PEGDA) under the UV light. Hydrogels were
      characterized by ATR-FTIR, SEM and XRD analyses. Mechanical performance of the
      hydrogels was determined by universal mechanical tester. Cytotoxicity tests for
      hydrogels were conducted with L929 cell lines to determine cellular
      compatibility. Swelling tests were carried out to investigate the water uptake
      capacity of hydrogels. Amoxicillin which could be used for treatment of gastric
      ulcer was selected as the model drug. The release of amoxicillin was provided at
      simulated gastric (pH: 1.2) and intestinal media (pH: 7.4) in efficient and
      controlled manner. All results visualized that the obtained pH-sensitive chitosan
      based hydrogel with enhanced mechanical properties could be a potential candidate
      as a drug carrier for treatment of gastric ulcer in the future applications.

PMID- 29352936
TI  - Freeze dried chitosan acetate dressings with glycosaminoglycans and traxenamic
      acid.
AB  - Bleeding control plays an important role to increase survival in the early phase
      after a traumatic event. The aim of present work was the development of
      hemostatic sponge-like dressings based on chitosan, in association with
      glycosaminoglycans (GAG) (chondroitin sulfate or hyaluronic acid) and the
      improvement of their hemostatic performance by loading tranexamic acid (TA). The
      dressings were prepared by lyophilizazion and were characterized for mechanical,
      hydration, bioadhesion properties and morphology. Moreover, FTIR analysis was
      performed to understand the interactions between the different polyelectrolytes
      present in the dressings. Clotting was investigated in vitro by using rat whole
      blood. Moreover, in vitro biocompatibility and proliferation were evaluated
      towards fibroblasts. Ex vivo proliferation properties were assessed by using
      human skin. All the dressings were characterised by mechanical, hydration and
      bioadhesion properties suitable to be applied on bleeding wounds and to absorb
      bleeding or wound exudate, avoiding tissue dehydration. TA release was fast; TA
      and chitosan showed a synergic effect to speed up clotting. The dressings were
      biocompatible and able to sustain cell proliferation in vitro and ex vivo in
      human skin. In conclusion, sponge-like dressings based on chitosan and GAG and
      loaded with TA are an effective tool to enhance hemostasis and healing in
      bleeding wounds.

PMID- 29352937
TI  - Synthesis, thermal properties and cell-compatibility of photocrosslinked
      cinnamoyl-modified hydroxypropyl cellulose.
AB  - Biocompatibility of cinnamoyl-modified carbohydrate materials is not well-known,
      while they are attracting attention as a photoreactive material. In order to
      investigate biocompatible properties of cinnamoyl-modified carbohydrate,
      hydroxypropyl cellulose (HPC) was reacted with cinnamoyl chloride to yield
      cinnamoyl-modified HPC (HPC-C) for a cell proliferation test. HPC-Cs with three
      different degrees of substitution (DS) were prepared by changing a feed ratio of
      cinnamoyl chloride to HPC. The DS of the products ranged from 1.3 to 3.0 per one
      hydroxylpropyl anhydroglucose unit. Thermal analysis using DSC and TGA showed
      that the HPC-C with higher DS has a glass transition temperature and higher
      thermal stability. Ultraviolet (UV) light was irradiated on the HPC-C thin films,
      and changes in the UV-vis spectrum of the films were examined. In the course of
      UV irradiation, the absorbance at 280 nm was reduced. Fibroblast cells were
      cultured on the photocrosslinked HPC-C films, and cell growth was examined. The
      cell proliferation test revealed that the photocrosslinked HPC-C films have good
      compatibility with fibroblast cells.

PMID- 29352938
TI  - DMTMM-mediated amidation of alginate oligosaccharides aimed at modulating their
      interaction with proteins.
AB  - Alginate oligosaccharides (AOS) with a weight average molecular weight of 5 kDa
      were efficiently amidated with amino acids and carbohydrates in aqueous media in
      the presence of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium
      chloride (DMTMM). Here, alanine, leucine, serine, as well as mannose and
      rhamnose, were amidated at high yields with a good control of the degree of
      substitution (DS). Amino acid- and carbohydrate-grafted AOS showed improved
      stability against degradation by alginate lyases having different specificities.
      This enzyme resistance was correlated with the DS: hydrolysis was reduced by 60
      70% for low DS (0.1), whereas AOS with DS ranging from 0.4 to 0.6 remained
      unhydrolyzed. Competitive inhibition assays demonstrated multivalent binding of
      mannose-amidated AOS to concanavalin A lectin. A 178-fold affinity enhancement
      was observed for AOSMan-0.38 (DS 0.38) over alpha-methyl-mannoside with an IC50
      of 5.6 MUM, lending further evidence for the promising potential of AOS as
      multivalent scaffolds.

PMID- 29352939
TI  - Paenibacillus panacisoli enhances growth of Lactobacillus spp. by producing
      xylooligosaccharides in corn stover ensilages.
AB  - The knowledge about the association of lignocellulosic biomass-degrading microbes
      with lactic acid bacteria (LAB) in ensilages is still limited. Paenibacillus
      strains are important microbes in sustainable agriculture. Here, P. panacisoli
      SDMCC050309 was isolated from ensiled corn stover and used as an example to
      investigate the effects on LAB. This strain produced at least 7 xylanases, and
      two of them were purified and characterized. Temperature and pH optima were
      determined to be 55  degrees C and 8.0 for Xyn10 and 40  degrees C and 7.0 for
      Xyn11, respectively. They could degraded larch wood xylan and alkali-pretreated
      corn stover into xylooligosaccharides (XOS). Using the produced XOS to culture
      Lactobacillus brevis SDMCC050297 and L. parafarraginis SDMCC050300, both of them
      grew well with high level of acetic acid production. The same phenomenon was
      observed when co-culturing those two Lactobacillus strains with P. panacisoli
      SDMCC050309. Therefore, P. panacisoli enhances growth of LAB by producing XOS in
      corn stover ensilages.

PMID- 29352940
TI  - PEGylated chitosan nanoparticles with embedded bismuth sulfide for dual
      wavelength fluorescent imaging and photothermal therapy.
AB  - It is of great significance to construct multifunctional nanosystems for
      simultaneous imaging and therapy of cancer cells. Herein, PEGylated chitosan
      nanoparticles with embedded bismuth sulfide were facilely fabricated via reverse
      microemulsion method for fluorescent imaging and photothermal therapy of HepG2
      cells. The obtained BSA-Bi2S3-CG-PEG nanospheres revealed dual-wavelength
      fluorescence, which were spectrally isolated from the bioautofluorescence.
      Moreover, they demonstrated remarkable photothermal conversion efficiency and
      stability. Importantly, these small BSA-Bi2S3-CG-PEG nanoparticles shown a zeta
      potential of + 42.3 mV, which could rapidly get into HepG2 cells and locate in
      the cytoplasm and nuclei of cells. Based on their excellent photothermal effect
      and high cellular uptake, BSA-Bi2S3-CG-PEG nanoparticles could efficiently kill
      HepG2 cells under an 808 nm laser irradiation. This construction strategy can be
      used for preparation of fluorescent chitosan nanoparticles with other therapeutic
      agents embedded, which would provide a versatile platform for dual-wavelength
      fluorescent imaging guided therapy of cancer.

PMID- 29352941
TI  - Preparation and characterization of PVA/nanocellulose/Ag nanocomposite films for
      antimicrobial food packaging.
AB  - Antimicrobial packaging is an area of emerging interest and is rapidly expanding
      with application of nanotechnology. The present work investigates the effect of
      nanocellulose (NC) and Ag NPs on the physical, mechanical and thermal properties
      of PVA nanocomposite films. The tensile strength of PVA was improved from 5.52 +/
      0.27 MPa to 12.32 +/- 0.61 MPa when filled with 8 wt% of NC. Nanocomposite films
      exhibited strong antibacterial activity against both Staphylococcus aureus (MRSA)
      and Escherichia coli (DH5-alpha). The maximum inhibition zone at 0.5 g Ag NPs
      with 12 wt% NC against DH5-alpha was 14 +/- 0.70 mm. While, the maximum
      inhibition zone at 0.3 g Ag NPs for 16 wt% NC was 13.6 +/- 0.68 mm against MRSA.
      Moreover, nanocomposites films have no cytotoxicity effect on HepG2 and cell
      viability was more than 90%. Based on mechanical properties and antibacterial
      potential of the developed nanocomposite films, it can be envisaged to use these
      films for packaging applications.

PMID- 29352942
TI  - Comparative study of molecular recognition of folic acid subunits with
      cyclodextrins.
AB  - The complexation of pteroic acid and pterine, subunits of folic acid, with native
      cyclodextrins (alpha-, beta-, and gamma-CDs) was studied in solution (UV-vis),
      and in the solid state (thermal analysis, IR and Raman). UV-vis titrations at pH
      = 7.4 provided data regarding stoichiometry of the formed complexes as well as
      their associations constants. Stability of the complexes increases in the series:
      gamma-CD < beta-CD << alpha-CD for pterine, and gamma-CD < alpha-CD << beta-CD
      for pteroic acid. The mode of complexation was further exploited by molecular
      modeling studies (docking studies, PM6) showing additionally changes in
      conformation of pteroic acid upon complexation. Comparison of the association
      constants of the complexes of pterine and pteroic acid with native cyclodextrins
      with data obtained for analogous complexes with folic acid shows that all folic
      acid complexes are less stable than those formed from its subunits.

PMID- 29352943
TI  - How does temperature govern mechanisms of starch changes during extrusion?
AB  - Potato and pea starches were processed on a twin-screw extruder under various
      moisture and thermomechanical conditions, chosen to keep material temperature Te
      close to starch melting temperature, Tm, whilst avoiding die expansion. Extruded
      rods were analysed by asymmetrical flow field flow fractionation coupled with
      light scattering, X-ray diffraction, DSC, and light microscopy with image
      analysis. Molar mass of extruded materials decreased more for potato than for pea
      starch, when specific mechanical energy SME increased, likely because of larger
      amylopectin sensitivity to shear. No crystallinity was detected when DeltaT = (Tm
      Te) <= 0. Residual gelatinization enthalpy DeltaHg decreased with DeltaT. As
      illustrated by larger DeltaT values for DeltaHg = 0, decreasing moisture favored
      melting, likely by increasing solid friction. The fraction of granular remnants
      of potato starch was inversely correlated to SME. These results could be
      explained by considering starch melting during extrusion as a suspension of solid
      particles embedded in a continuous amorphous matrix.

PMID- 29352944
TI  - Fabrication of cellulose nanowhiskers reinforced chitosan-xylan nanocomposite
      films with antibacterial and antioxidant activities.
AB  - Antibacterial and antioxidant chitosan-xylan/cellulose nanowhiskers (CNW)
      nanocomposite films were successfully prepared using CNW as nanofillers. The
      structure and morphology of the nanocomposite films were investigated by Fourier
      transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), and scanning
      electron microscopy (SEM). The optical transmittance, thermal stability,
      mechanical property, and swelling property of the nanocomposite films were also
      evaluated. These results revealed the microstructure of the films and confirmed
      the good miscibility between chitosan-xylan and CNW. The improvements of tensile
      strength and elongation at break of the nanocomposite films confirmed the
      reinforcement effects of CNW. Moreover, the inhibitory effects against S. aureus
      and E. coli and the ABTS+ scavenging activity indicated antibacterial and
      antioxidant functions of the nanocomposite films. In this work, the prepared
      chitosan-xylan/CNW nanocomposite films, combined the antibacterial property of
      chitosan, the antioxidant property of xylan, and good mechanical property of CNW,
      could be potentially applied in food and health-related areas.

PMID- 29352945
TI  - Silylation and characterization of microcrystalline cellulose isolated from
      indonesian native oil palm empty fruit bunch.
AB  - Silylation of microcrystalline cellulose (MCC), isolated from Indonesian native
      oil palm empty fruit bunch (OPEFB), using aminosilane compound synthesized
      through aminolysis of 3-glycidoxypropyltrimethoxysilane (GPTMS) with
      ethylenediamine (EDA) has been conducted in this study. Generally, there are
      three steps performed to isolate MCC before silylation process, i.e. bleaching,
      alkaline treatment and acid hydrolysis. All products resulted from bleaching,
      alkaline and acid hydrolysis treatments were characterized using Fourier
      Transform Infrared (FTIR) spectroscopy. Two conditions were optimized in this
      study which they were an acid concentration in hydrolysis process and aminosilane
      ratio in silylation process. The preliminary study regarding optimizing acid
      hydrolysis process by varying sulfuric acid concentration was obtained an optimum
      sulfuric acid concentration by 45% having highest crystallinity index (CI)
      measured using x-ray diffraction (XRD) data. The morphological structure of MCC
      was rod-like crystalline structure confirmed by transmission electron microscopy
      (TEM). The silylating agent was varied in this study with the ratio to MCC by
      1:1, 3:1 and 5:1 mmol g-1. Based on loading analysis, the aminosilane with ratio
      1:1 mmol g-1 was noted as optimum concentration having high loading yield by
      79.2%. Effect of silylation on MCC properties was, on the one hand, it decreased
      the CI and crystallite size, however, on the other hand, it increased the surface
      area and pore volume.

PMID- 29352946
TI  - Redox/enzyme sensitive chondroitin sulfate-based self-assembled nanoparticles
      loading docetaxel for the inhibition of metastasis and growth of melanoma.
AB  - In this report, redox/enzyme responsive chondroitin sulfate-ss-deoxycholic acid
      (CSCD) conjugates were synthesized using cystamine as the linkage which could
      self-assemble to form self-assembled nanoparticles (175.6 + 5.2 nm) in the
      aqueous environment. Docetaxel (DTX) was loaded in nanoparticles with desired
      loading efficiency for the inhibition of tumor growth and metastasis of melanoma.
      Interestingly, nanoparticles were demonstrated to respond to hyaluronidase-1
      (Hyal-1) which could degrade chondroitin sulfate (CS) backbones. In this case, we
      designed dual-sensitive nanoparticles with enhanced drug release pattern under
      the presence of glutathione (GSH)/Hyal-1. Compared with Taxotere(r), CSCD
      nanoparticles significantly improved the DTX distribution in tumors and lungs
      with about 4.4-fold higher area-under-the-curve (AUC) value. In situ tumor volume
      and pulmonary metastatic formation were reduced upon the administration of DTX
      loaded CSCD nanoparticles via DTX-induced apoptosis and decreased metastasis
      promotion protein expression. With only minor cytotoxicity, CSCD nanoparticles
      could be promising nano-drug delivery systems for successful management of
      melanoma.

PMID- 29352947
TI  - Novel organic/inorganic hybrid flower-like structure of selenium nanoparticles
      stabilized by pullulan derivatives.
AB  - We proudly present the first organic/inorganic hybrid pullulan/SeNPs hybrid
      microflower material obtained using a simple and bio-inspired strategy. The
      chemical structures of pullulan, folic acid decorated cationic pullulan (FA-CP)
      were designed for stabilizing selenium nanoparticles (SeNPs). SeNPs stabilized by
      FA-CP hybrid microflowers were observed after the addition of a cysteine
      hydrochloride solution into the solution mixture of Na2SeO3 and FA-CP. We
      suggested that the concentrations of cysteine and FA-CP were the key factors for
      the formation of flower-like structure. In addition, the formation mechanism of
      the microflowers was tentatively identified as anisotropic hierarchical growth.
      The microflowers exhibited effective drug adsorption with the loading capacity of
      142.2 mg g-1 for doxorubicin which was three times higher than that for the
      doxorubicin-loaded spherical SeNPs and showed more potent activity against cancer
      cells while showing less toxicity against normal cells. These data demonstrated
      that the microflower-like FA-CP/SeNPs structure could be a candidate anticancer
      drug template in drug delivery systems.

PMID- 29352948
TI  - Laccase-TEMPO-mediated air oxidation of galactomannan for use as paper
      strengthening agent.
AB  - In this study, galactomannans, which are a type of plant polysaccharide, were
      oxidized by using a laccase and TEMPO-mediated air-oxidation system. The
      influence of the oxidation conditions, including the laccase doses, oxidation
      times, and amounts of oxidizing system, on the properties of the paper were
      investigated. The results showed that the oxidized galactomannans could improve
      the paper properties. The optimal conditions were as follows: a 60 U/g enzyme
      dosage; 6-h oxidization time and a 0.1 g TEMPO dosage. When compared with the
      control paper, the tensile index and folding endurance have been improved by
      28.42% and 88.02%, respectively, when 1.5% oxidized galactomannans were used, and
      for the recycled paper, the increment could reach 126.97% and 43.85%
      correspondingly. Also, the results of the elemental, FT-IR, and CP/MAS13C NMR
      analyses demonstrated that some of the hydroxyl of the galactomannans had been
      transformed into the carboxyl and aldehyde groups.

PMID- 29352949
TI  - Editorial Comment.

PMID- 29352950
TI  - Editorial Comment.

PMID- 29352951
TI  - Reply by Authors.

PMID- 29352952
TI  - Editorial Comment.

PMID- 29352953
TI  - Reply.

PMID- 29352955
TI  - Endoscopy Examination Time: Longer Is Really Better?

PMID- 29352954
TI  - Unexpected Findings in a Patient With Cancer of Unknown Primary Syndrome.

PMID- 29352956
TI  - What Are the Benefits of Anticoagulation for Portal Vein Thrombosis in
      Individuals With Cirrhosis?

PMID- 29352957
TI  - The Fragility of Probiotic Bifidobacterium longum NCC3001 Use for Depression in
      Patients With Irritable Bowel Syndrome.

PMID- 29352958
TI  - Portal Vein Thromboses in Cirrhosis: To Treat or Not to Treat?

PMID- 29352959
TI  - A Flat Tire in the Colon.

PMID- 29352960
TI  - Persistent Fever and Abdominal Pain in a Young Woman With Budd-Chiari Syndrome.

PMID- 29352961
TI  - An Unusual Cause of Abdominal Pain in a Young, Hypertensive Female.

PMID- 29352962
TI  - Improved systemic metabolism and adipocyte biology in miR-150 knockout mice.
AB  - INTRODUCTION: Short non-coding micro-RNAs (miRNAs) are post-transcriptional
      factors that directly regulate protein expression by degrading or inhibiting
      target mRNAs; however, the role of miRNAs in obesity and cardiometabolic disease
      remains unclarified. Based on our earlier study demonstrating that miR-150
      influences lipid metabolism, we have studied effects of miR-150 on systemic
      metabolism and adipocyte biology. MATERIALS AND METHODS: Metabolic phenotypes
      including body weight, food intake, body composition, glucose tolerance and
      insulin sensitivity were assessed in WT and global miR-150 KO male mice fed a
      high-fat diet. Molecular changes in epididymal adipose tissue were evaluated
      through qRT-PCR and Western blotting. RESULTS: miR-150 KO mice displayed lower
      body weight characterized by a reduction in % fat mass while % lean mass was
      increased. Lower body weight was associated with reduced food consumption and an
      increase in circulating leptin concentrations, as well as enhanced insulin
      sensitivity and glucose tolerance compared with WT mice. Absence of miR-150
      resulted in increased mTOR expression known to participate in increased leptin
      production leading to reduction of food intake. Expression of PGC-1alpha, another
      target gene of miR-150, was also increased together with upregulation of
      PPARalpha and glycerol kinase in adipose tissue as well as other genes
      participating in triglyceride degradation and lipid oxidation. CONCLUSION: miR
      150 KO mice showed metabolic benefits accompanied by reduced body weight,
      decreased energy intake, and enhanced lipid metabolism. miR-150 may represent
      both a biomarker and novel therapeutic target regarding obesity and insulin
      resistance.

PMID- 29352964
TI  - C24-hydroxylated stigmastane derivatives as Liver X Receptor agonists.
AB  - Phytosterols are stucturally correlated to the endogenous ligands of Liver X
      Receptor (LXR), a ligand-activated nuclear receptor that has emerged as an
      attractive drug target due to its ability to integrate metabolic and inflammatory
      signaling. Natural and semi-synthetic phytosterol derivatives characterized by
      the presence of side-chain oxygenated functions have shown to be able to modulate
      LXR activity. Here, we describe the efficient synthesis of four stigmastane
      derivatives, endowed with a hydroxyl group at C24 position, namely (24R)- and
      (24S)-stigmasta-5,28-diene-3beta,24-ols (also referred to as saringosterols, 10a
      and 10b) and (24R)- and (24S)-stigmasta-5-ene-3beta,24-ols (11a and 11b),
      starting from the readily available stigmasterol. Thanks to X-ray crystallography
      the absolute configuration of the newly created chiral centers was definitively
      assigned for all the four compounds. The subsequent luciferase assays with GAL-4
      chimeric receptors evidenced the ability of the two 24(S)-epimers, 10b and 11b,
      to interact with LXRs, showing the same degree of affinity as (22R)
      hydroxycholesterol (1). With regard to the isoform selectivity both the
      derivatives 10b and 11b showed a preference for LXRbeta, up to 4-fold in terms of
      efficacy for 11b. The gene expression profiling of (24S)-stigmasta-5,28-diene
      3beta,24-ol (10a) and (24S)-stigmasta-5-ene-3beta,24-ol (11a) demonstrated the
      capability of both the compounds to induce the expression of four well-known LXR
      target genes, such as ABCA1, SREBP1c, FASN, and SCD1 in U937 monocytic cell line,
      thus supporting the hypothesis they were LXR positive modulators.

PMID- 29352965
TI  - Establishment of a protocol for the isolation of feline pancreatic islets.
AB  - Diabetes mellitus is a common endocrinopathy in cats that is associated with
      pancreatic islets lesions. Research on isolated islets contributed to the
      understanding of the pathophysiology of human diabetes. Therefore, by improving
      the existing methods of isolation in cats, we aimed at increasing islet yield,
      purity and viability of feline isolated islets. Islet isolation was accomplished
      by pancreas perfusion with 80ml of Collagenase type IV through the pancreatic
      duct at the site of the major papilla. The enzymatic digestion was combined with
      mechanical disruption and controlled by dithizone staining. Purification was
      performed by filtration and handpicking. Purified islets were plated on
      extracellular matrix pre-coated plates and cultured for 48h. Feline islets with a
      high degree of viability and purity were isolated and cultured for the first
      time. Although the percentage of islet free from the acinar tissue relative to
      the total number of isolated islets was low compared to other species, the
      suggested protocol represents a promising progress in the procedure of islet
      isolation in cats.

PMID- 29352966
TI  - Polyphyllin G exhibits antimicrobial activity and exerts anticancer effects on
      human oral cancer OECM-1 cells by triggering G2/M cell cycle arrest by
      inactivating cdc25C-cdc2.
AB  - Plant natural products have long been considered to be important sources of
      bioactive molecules. A large number of antimicrobial and anticancer agents have
      been isolated form plants. In the present study we evaluated the antimicrobial
      and anticancer activity of a plant derived secondery metabolite, Polyphyllin G.
      The results of antibacterial assays showed that Polyphyllin G prevented the
      growth of both Gram-positive and Gram-negative bacteria with minimum inhibitory
      concentrations (MICs) ranging from 13.1 to 78 MUg/ml. Antifungal activity
      measured as inhibition of mycelium growth ranged between 38.32 and 56.50%.
      Further Polyphyllin G was also evaluated against a panel of cancer cell lines.
      The IC50 of Polyphyllin G ranged from 10 to 65 MUM. However the IC50 of
      Polyphyllin G was found to be comparatively high (120 MUM) against the normal FR2
      cancer cell line. The lowest IC50 of 10 MUM was found against the oral cancer
      cell line OECM-1. Therefore further studies were carried out on this cell line
      only. Our results indicated that Polyphyllin G induced cell arrest in oral cancer
      OECM-1 cells by inactivation of cdc25C-cdc22 via ATM-Chk 1/2 stimulation.
      Therefore, we propose that Polyphyllin G might prove a lead molecule in the
      management of oral cancers and at the same time may prevent the growth of
      opportunistic microbes.

PMID- 29352963
TI  - Three-dimensional visualization of extracellular matrix networks during murine
      development.
AB  - The extracellular matrix (ECM) plays a crucial role in embryogenesis, serving
      both as a substrate to which cells attach and as an active regulator of cell
      behavior. However, little is known about the spatiotemporal expression patterns
      and 3D structure of ECM proteins during embryonic development. The lack of
      suitable methods to visualize the embryonic ECM is largely responsible for this
      gap, posing a major technical challenge for biologists and tissue engineers.
      Here, we describe a method of viewing the 3D organization of the ECM using a
      polyacrylamide-based hydrogel to provide a 3D framework within developing murine
      embryos. After removal of soluble proteins using sodium dodecyl sulfate, confocal
      microscopy was used to visualize the 3D distribution of independent ECM networks
      in multiple developing tissues, including the forelimb, eye, and spinal cord.
      Comparative analysis of E12.5 and E14.5 autopods revealed proteoglycan-rich
      fibrils maintain connections between the epidermis and the underlying tendon and
      cartilage, indicating a role for the ECM during musculoskeletal assembly and
      demonstrating that our method can be a powerful tool for defining the
      spatiotemporal distribution of the ECM during embryogenesis.

PMID- 29352967
TI  - Product specificity of fungal 8R- and 9S-dioxygenases of the peroxidase
      cyclooxygenase superfamily with amino acid derivatized polyenoic fatty acids.
AB  - Pathogenic fungi express fatty acid dioxygenases (DOX) fused to cytochromes P450
      with diol or allene oxide synthase activities. The orientation of the fatty acids
      in the active sites of DOX was investigated with amino acid conjugates of 18:3n-3
      and 18:2n-6. 9S-DOX-allene oxide synthase (AOS) oxidized the Gly, Ile, and Trp
      derivatives at C-9, which suggests that these conjugates enter the substrate
      recognition site with the omega end in analogy with fatty acids bound to
      cyclooxygenases and coral 8R-lipoxygenase (8R-LOX). In contrast, 7,8-diol
      synthases (7,8-LDS), 5,8-LDS, and 8R-DOX-AOS oxidized the Gly conjugates in most
      case only to small amounts of metabolites, but with retention of hydrogen
      abstraction at C-8 and relatively minor hydrogen abstraction at C-11. The Ile and
      Trp conjugates were not oxidized at C-8, and often insignificantly at C-9/C-13.
      The 8-DOX domains of these enzymes likely position the carboxyl group of
      substrates at the end of the active site in analogy with plant alpha-DOX and 9
      LOX. Tyr radicals of the 9S-DOX and 8R-DOX domains catalyze antarafacial hydrogen
      abstraction and oxygen insertion in 18:3n-3. This occurs by abstraction of the
      proR and proS hydrogens at C-11 and C-8, respectively, in agreement with
      different "head to tail" orientation in the active site.

PMID- 29352968
TI  - Children with dyslexia show a reduced processing benefit from bimodal speech
      information compared to their typically developing peers.
AB  - During information processing, individuals benefit from bimodally presented
      input, as has been demonstrated for speech perception (i.e., printed letters and
      speech sounds) or the perception of emotional expressions (i.e., facial
      expression and voice tuning). While typically developing individuals show this
      bimodal benefit, school children with dyslexia do not. Currently, it is unknown
      whether the bimodal processing deficit in dyslexia also occurs for visual
      auditory speech processing that is independent of reading and spelling
      acquisition (i.e., no letter-sound knowledge is required). Here, we tested school
      children with and without spelling problems on their bimodal perception of video
      recorded mouth movements pronouncing syllables. We analyzed the event-related
      potential Mismatch Response (MMR) to visual-auditory speech information and
      compared this response to the MMR to monomodal speech information (i.e., auditory
      only, visual-only). We found a reduced MMR with later onset to visual-auditory
      speech information in children with spelling problems compared to children
      without spelling problems. Moreover, when comparing bimodal and monomodal speech
      perception, we found that children without spelling problems showed significantly
      larger responses in the visual-auditory experiment compared to the visual-only
      response, whereas children with spelling problems did not. Our results suggest
      that children with dyslexia exhibit general difficulties in bimodal speech
      perception independently of letter-speech sound knowledge, as apparent in altered
      bimodal speech perception and lacking benefit from bimodal information. This
      general deficit in children with dyslexia may underlie the previously reported
      reduced bimodal benefit for letter-speech sound combinations and similar findings
      in emotion perception.

PMID- 29352969
TI  - Unusual yellow scaly colonic mucosal appearance: Tangier disease.

PMID- 29352970
TI  - An uncommon cecal bulge caused by a large appendiceal mucinous neoplasm.

PMID- 29352972
TI  - Double percutaneous endoscopic gastrostomies for a refractory duodenal fistula.

PMID- 29352971
TI  - Magnetic anchor-guided endoscopic submucosal dissection for gastric lesions (with
      video).
AB  - BACKGROUND AND AIMS: The feasibility of magnetic anchor-guided endoscopic
      submucosal dissection (MAG-ESD) using a neodymium magnet for gastric lesions has
      not been clarified. The aim of study was to evaluate the feasibility of MAG-ESD
      using neodymium magnets while treating gastric lesions. METHODS: This prospective
      trial was conducted at the Yamashita Hospital. MAG-ESD was performed for 50
      gastric lesions using an insulated-tip knife. The magnetic anchor consisted of an
      internal neodymium magnet attached to a hemoclip with 3-0 silk. The external and
      internal magnets were made from the neodymium magnet. The feasibility of traction
      using MAG-ESD, en bloc resection rate, complete en bloc resection rate, time
      required for preparation and attaching the magnetic anchor, procedure time, rate
      of retrieval of the magnetic anchors, and adverse events were evaluated. RESULTS:
      Fifty patients (median lesion size, 20 mm [range, 5-100]) were enrolled. MAG-ESDs
      were successfully performed for all 50 gastric lesions. Adequate counter-traction
      was obtained using the external magnet. En bloc resections were achieved and
      complete en bloc resections confirmed in all cases without adverse events.
      Attaching the magnetic anchor required a median of 6 minutes (range, 2-14). The
      median procedure time was 49 minutes (range, 15-301), and the magnetic anchors
      could be retrieved in all cases. CONCLUSIONS: This study clearly demonstrated the
      feasibility of this MAG-ESD in the stomach. We hope this procedure will
      facilitate the resection of difficult lesions. (Clinical trial registration
      number: UMIN000024100.).

PMID- 29352973
TI  - The Senegal urban reproductive health initiative: a longitudinal program impact
      evaluation.
AB  - OBJECTIVES: This paper presents the impact of key components of the Senegal Urban
      Reproductive Health Initiative, including radio, television, community-based
      activities, Muslim religious-leader engagement and service quality improvement on
      modern contraceptive use by all women and the sub-sample of poor women. STUDY
      DESIGN: This study uses baseline (2011) and endline (2015) longitudinal data from
      a representative sample of urban women first surveyed in 2011 to examine the
      impact of the Initiative's demand- and supply-side activities on modern
      contraceptive use. RESULTS: By endline, there was increased exposure to radio and
      television programming, religious leaders speaking favorably about contraception,
      and community-based initiatives. In the same period, modern contraceptive use
      increased from 16.9% to 22.1% with a slightly larger increase among the poor
      (16.6% to 24.1%). Multivariate analyses demonstrate that women exposed to
      community-based activities were more likely to use modern contraception by
      endline (marginal effect (ME): 5.12; 95% confidence interval (CI): 2.50-7.74)
      than those not exposed. Further, women living within 1 km of a facility with
      family planning guidelines were more likely to use (ME: 3.54; 95% CI: 1.88-5.20)
      than women without a nearby facility with guidelines. Among poor women, community
      based activities, radio exposure (ME: 4.21; 95% CI: 0.49-7.93), and living close
      to program facilities (ME: 4.32; 95% CI: 0.04-8.59) impacted use. CONCLUSIONS:
      Community-based activities are important for reaching urban women, including poor
      women, to achieve increased contraceptive use. Radio programming is also an
      important tool for increasing demand, particularly among poor women. Impacts of
      other program activities on contraceptive use were modest. IMPLICATIONS: This
      study demonstrates that community-based activities led to increased modern
      contraceptive use among all women and poor women in urban Senegal. These findings
      can inform future programs in urban Senegal and elsewhere in francophone Africa.

PMID- 29352974
TI  - Chrysin, a natural and biologically active flavonoid suppresses tumor growth of
      mouse B16F10 melanoma cells: In vitro and In vivo study.
AB  - Chrysin (5,7-dihydroxyflavone) is a natural and biologically active compound
      which has many biological activities as an anticancer agent. The current report
      is aimed at finding out whether the antitumor potential of chrysin, evidenced in
      vitro and in vivo, is linked or not to its effect on immunological mechanisms of
      melanoma-bearing mice. Chrysin-treated B16F10 cells were analyzed for their
      metabolic rate and apoptotic potentials. In vivo, BALB/c mice received a
      subcutaneous injection of B16F10 melanoma cells prior to antitumor treatments
      with chrysin (50 mg/kg b.w) for 14 days and 21 days. The results showed that
      chrysin inhibited cancer cell growth at a dose-dependent manner by inducing
      apoptosis and cell cycle arrest at G2/M phase. Moreover, chrysin suppressed
      melanoma tumor growth at an average of 60% (after 14 days of treatment) and 71%
      (after 21 days of treatment) compared to the tumor-bearing group. Furthermore,
      chrysin treatment increased the cytotoxic activity of NK, CTL and macrophages.
      The findings showed that chrysin antitumor action on the murine melanoma model
      was very promising, suggesting that chrysin could be a potentially good candidate
      for future use in alternative anti-melanoma treatments.

PMID- 29352976
TI  - Anterior Segment Imaging for Angle Closure.
AB  - PURPOSE: To summarize the role of anterior segment imaging (AS-imaging) in angle
      closure diagnosis and management, and the possible advantages over the current
      standard of gonioscopy. DESIGN: Literature review and perspective. METHODS:
      Review of the pertinent publications with interpretation and perspective in
      relation to the use of AS-imaging in angle closure assessment focusing on
      anterior segment optical coherence tomography and ultrasound biomicroscopy.
      RESULTS: Several limitations have been encountered with the reference standard of
      gonioscopy for angle assessment. AS-imaging has been shown to have performance in
      angle closure detection compared to gonioscopy. Also, imaging has greater
      reproducibility and serves as better documentation for long-term follow-up than
      conventional gonioscopy. The qualitative and quantitative information obtained
      from AS-imaging enables better understanding of the underlying mechanisms of
      angle closure and provides useful parameters for risk assessment and possible
      prediction of the response to laser and surgical intervention. The latest
      technologies-including 3-dimensional imaging-have allowed for the assessment of
      the angle that simulates the gonioscopic view. These advantages suggest that AS
      imaging has a potential to be a reference standard for the diagnosis and
      monitoring of angle closure disease in the future. CONCLUSIONS: Although
      gonioscopy remains the primary method of angle assessment, AS-imaging has an
      increasing role in angle closure screening and management. The test should be
      integrated into clinical practice as an adjunctive tool for angle assessment. It
      is arguable that AS-imaging should be considered first-line screening for
      patients at risk for angle closure.

PMID- 29352975
TI  - Pinocembrin from Penthorum chinense Pursh suppresses hepatic stellate cells
      activation through a unified SIRT3-TGF-beta-Smad signaling pathway.
AB  - The inactivation of hepatic stellate cells (HSCs) has been verified to be an
      effective therapeutic strategy for treatment of liver fibrosis. Penthorum
      chinense Pursh has been widely used to protect liver in China; while, the role of
      P. chinense Pursh in treatment of liver fibrosis is still unexplored. In the
      current study, the aqueous extract of P. chinense Pursh (PCE) was found to
      suppress the expressions of fibrotic markers, including collagen I and alpha
      smooth muscle actin (alpha-SMA), in human HSCs (LX-2); and its major active
      constituent, pinocembrin (PIN), was discovered to inhibit the expressions of
      fibrotic markers in LX-2 cells and rat HSCs (HSC-T6). Further study indicated
      that PIN suppressed the activation of LX-2 and HSC-T6 cells through elevating the
      expression and activity of silent mating type information regulation 2 homolog 3
      (SIRT3). Via SIRT3, PIN activated superoxide dismutase 2 (SOD2), to alleviate the
      accumulation of reactive oxygen species (ROS) and inhibit phosphoinositide 3
      kinase (PI3K)-protein kinase B (Akt) signaling, resulting in decreased production
      of transforming growth factor-beta (TGF-beta) and nuclear translocation of the
      transcription factor Sma- and Mad-related proteins (Smad). Furthermore, PIN
      activated glycogen synthase kinase 3beta (GSK3beta) through SIRT3, to enhance
      Smad protein degradation. Taken together, PCE and PIN were identified as
      potential anti-fibrotic agents, which might be well developed as a candidate for
      treatment of liver fibrosis.

PMID- 29352977
TI  - Paclitaxel inhibited lysozyme fibrillation by increasing colloidal stability
      through formation of "off-pathway" oligomers.
AB  - Protein fibrillation is a challenging issue in medicine, causing many diseases,
      and an impediment to pharmaceutics and protein industry. Many chemicals,
      especially polyphenol compounds and aromatic small molecules, have been widely
      used as an effective strategy to combat protein fibril formation. Hence,
      understanding mechanisms of fibrillation inhibition and contributing forces in
      this process are significant. In this study, the inhibitory effect of paclitaxel
      on lysozyme fibrillation was investigated with respect to thermal and colloidal
      stability. Fibrillation was monitored with ThT fluorescence, circular dichroism,
      and AFM; paclitaxel-lysozyme interaction with isothermal titration calorimetry
      and docking; thermal and colloidal stability with differential scanning
      calorimetry and zeta-pulse, respectively. Paclitaxel inhibited lysozyme
      fibrillation, and interacted with lysozyme through hydrogen bonds and van der
      Waals' interactions. The viability of PC12 cells retrieved as a result of
      fibrillation inhibition by paclitaxel. Hydrophobic forces dominantly shielded the
      aggregation-prone region of lysozyme and suppressed the effective interactions
      between lysozyme monomers. Although paclitaxel did not affect lysozyme's thermal
      stability, it increased lysozyme's colloidal stability by either increasing the
      surface charge density or charge distribution on lysozyme. In conclusion, our
      results suggest a model for paclitaxel's inhibitory role through two
      complementary steps driving to "off-pathway" oligomer formation and attenuation
      of fibril formation.

PMID- 29352978
TI  - Use of multimodality imaging and artificial intelligence for diagnosis and
      prognosis of early stages of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a major neurodegenerative disease and the most common
      cause of dementia. Currently, no treatment exists to slow down or stop the
      progression of AD. There is converging belief that disease-modifying treatments
      should focus on early stages of the disease, that is, the mild cognitive
      impairment (MCI) and preclinical stages. Making a diagnosis of AD and offering a
      prognosis (likelihood of converting to AD) at these early stages are challenging
      tasks but possible with the help of multimodality imaging, such as magnetic
      resonance imaging (MRI), fluorodeoxyglucose (FDG)-positron emission topography
      (PET), amyloid-PET, and recently introduced tau-PET, which provides different but
      complementary information. This article is a focused review of existing research
      in the recent decade that used statistical machine learning and artificial
      intelligence methods to perform quantitative analysis of multimodality image data
      for diagnosis and prognosis of AD at the MCI or preclinical stages. We review the
      existing work in 3 subareas: diagnosis, prognosis, and methods for handling
      modality-wise missing data-a commonly encountered problem when using
      multimodality imaging for prediction or classification. Factors contributing to
      missing data include lack of imaging equipment, cost, difficulty of obtaining
      patient consent, and patient drop-off (in longitudinal studies). Finally, we
      summarize our major findings and provide some recommendations for potential
      future research directions.

PMID- 29352979
TI  - Evaluation of sheep ovarian tissue cryopreservation with slow freezing or
      vitrification after chick embryo chorioallantoic membrane transplantation.
AB  - The aim of our investigations was to compare the effectiveness of two methods for
      cryopreservation of sheep ovarian tissue, slow freezing and vitrification. The
      quality of cryopreserved tissues was evaluated after 5 days of thawing and
      chorioallantoic membrane (CAM) transplantation. Follicular structure, stromal
      integrity and neovascularization were assessed. The areas of fibrosis and
      necrosis were measured using MICROVISIBLE software, and proliferation was
      assessed with Ki-67 immunostaning. After 5 days of culture, the proportion of
      primordial follicles decreased, whereas the primary and intermediary follicles
      increased insignificantly (p > .05). Only necrosis in the vitrified culture group
      increased significantly (p < .05). It was established also that 5 days CAM
      culture was not suitable methodology for detection of folliculogenesis.
      Follicular quality decreased after culture, but was better in fresh and slow
      frozen tissues than after vitrification (p < .05). Cellular proliferative
      activity fell, but it preserved to some extent in all groups. In conclusion,
      follicles was preserved better in grafted tissue after slow freezing than
      vitrification and stroma was more susceptible to ischemia in vitrified rather
      than conventional freezing in this view. Vitrification may not be a suitable
      alternative to the slow freezing.

PMID- 29352980
TI  - Effect of two cooling protocols on the post-thaw characteristics of Iberian ibex
      sperms.
AB  - The rate at which lethal intracellular ice forms during sperm cryopreservation is
      highly dependent on the cooling protocol. The present work compares two cooling
      protocols for use with Iberian ibex (Capra pyrenaica) sperm by assessing the
      effects on the motility, viability, and size of frozen-thawed sperm cells.
      Ejaculates, obtained from six adult ibex males via transrectal, ultrasound-guided
      massage of the accessory sex glands plus electroejaculation if necessary, were
      cooled via either 1) Protocol 1 (decelerating cooling), involving cooling in
      liquid nitrogen vapor from 5  degrees C to -35  degrees C (40  degrees C/min),
      from -35  degrees C to -65  degrees C (17  degrees C/min), and then from -65 
      degrees C to -85  degrees C (3  degrees C/min); or 2) Protocol 2 (accelerating
      cooling) involving cooling in a biological freezer from 5  degrees C to -5 
      degrees C (4  degrees C/min), from -5  degrees C to -110  degrees C (25  degrees
      C/min), and then from -110  degrees C to -140  degrees C (35  degrees C/min).
      Compared to fresh ejaculates, sperm quality at thawing was found to be reduced by
      both protocols (p < .05), but especially by Protocol 1. Sperm head size was also
      significantly reduced by both protocols, although the Protocol 1 sperm heads were
      also significantly smaller than those of Protocol 2 sperms heads (p < .05). In
      fresh sperm samples, clustering analyses revealed two subpopulations of sperms
      with different morphometric characteristics, SP1 with larger cells, and SP2 with
      smaller cells. Both cooling protocols caused reduction in the proportion of SP1
      cells, and an increase in the proportion of SP2 cells. In conclusion, the
      decelerating cooling protocol (Protocol 1) caused greater cryodamage to the sperm
      cells than the accelerating protocol (Protocol 2).

PMID- 29352981
TI  - Editorial.

PMID- 29352982
TI  - Inhibition of CYP3A by Antimalarial Piperaquine and Its Metabolites in Human
      Liver Microsomes With IVIV Extrapolation.
AB  - The potential of the antimalarial piperaquine and its metabolites to inhibit
      CYP3A was investigated in pooled human liver microsomes. CYP3A activity was
      measured by liquid chromatography-tandem mass spectrometry as the rate of 1'
      hydroxymidazolam formation. Piperaquine was found to be a reversible, potent
      inhibitor of CYP3A with the following parameter estimates (%CV): IC50 = 0.76 MUM
      (29), Ki = 0.68 MUM (29). In addition, piperaquine acted as a time-dependent
      inhibitor with IC50 declining to 0.32 MUM (28) during 30-min pre-incubation. Time
      dependent inhibitor estimates were kinact = 0.024 min-1 (30) and KI = 1.63 MUM
      (17). Metabolite M2 was a highly potent reversible inhibitor with estimated IC50
      and Ki values of 0.057 MUM (17) and 0.043 MUM (3), respectively. M1 and M5
      metabolites did not show any inhibitory properties within the limits of assay
      used. Average (95th percentile) simulated in vivo areas under the curve of
      midazolam increased 2.2-fold (3.7-fold) on the third which is the last day of
      piperaquine dosing, whereas for its metabolite M2, areas under the curve of
      midazolam increased 7.7-fold (13-fold).

PMID- 29352983
TI  - Parasitoid polydnaviruses and immune interaction with secondary hosts.
AB  - Polydnaviruses (PDVs) are obligatory symbionts with parasitoid wasps. The PDV
      virions are produced solely in wasp (the primary host) calyx cells. They are
      injected into caterpillar hosts (the secondary host) during parasitoid
      oviposition, where they express irreplaceable actions to ensure survival and
      development of wasp larvae. Some of PDV gene products suppress host immune
      responses while others alter host growth, metabolism or endocrine system. Here,
      we treat new findings on PDV gene products and their action on immunity within
      secondary hosts.

PMID- 29352984
TI  - SpCrus3 and SpCrus4 share high similarity in mud crab (Scylla paramamosain)
      exhibiting different antibacterial activities.
AB  - Type I crustins are crucial effectors of crustacean immune system. Various type I
      crustins with high sequence diversity possess different antimicrobial activities.
      To date, the mechanism on how the sequence diversity of type I crustins affects
      their antimicrobial activities is largely unclear, and how different crustins
      function together against bacterial invasion still remains unknown. In this
      study, we identified two novel type I crustins, namely, SpCrus3 and SpCrus4, from
      an economically important crab, Scylla paramamosain. Either SpCrus3 or SpCrus4
      was highly expressed in gill. After challenges with Vibrio parahemolyticus or
      Staphylococcus aureus, SpCrus4 was up-regulated, whereas SpCrus3 was down
      regulated. No significant expression change of SpCrus3 and SpCrus4 was observed
      after white spot syndrome virus injection, suggesting that these two genes may
      not participate in the antiviral immune responses. SpCrus3 and SpCrus4 had the
      common 5' terminus and high similarity of 66.06%, but SpCrus4 exhibited stronger
      antimicrobial activity than that of SpCrus3. Microorganism-binding assay results
      revealed that both SpCrus3 and SpCrus4 exhibited binding ability to all tested
      microorganisms. Furthermore, the polysaccharide-binding assay showed that these
      two proteins exhibited strong binding activity to bacterial polysaccharides, such
      as lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN).
      SpCrus3 and SpCrus4 exhibited stronger binding activity to LPS or LTA than to
      PGN. Moreover, SpCrus4 showed stronger binding activity to LTA than that of
      SpCrus3, which may be responsible for the significantly distinct antimicrobial
      activity between these two proteins. In addition, SpCrus4 displayed stronger
      agglutination activity against several kinds of microorganisms than that of
      SpCrus3. This increased agglutination activity may also contribute to the strong
      antibacterial activity of SpCrus4. On the basis of all these results, a possible
      antibacterial mode exerted by SpCrus3 and SpCrus4 was proposed as follows.
      SpCrus3 was highly expressed in normal crabs to maintain low-level antibacterial
      activity without bacterial challenges. When crabs were challenged with bacteria,
      large amount of SpCrus4 was generated to exhibit strong antibacterial activity
      against bacterial invasion. This study provides new insights to understand the
      antibacterial functions and mechanisms of type I crustins.

PMID- 29352985
TI  - Easy Suprapubic Tube Placement Using a Van Buren Sound.
AB  - OBJECTIVE: To place a suprapubic tube without using specialized instruments.
      Suprapubic cystostomy is a straightforward urological procedure, which
      nevertheless may become complicated if the equipment needed to perform the
      operation is unavailable. Nowadays, in most operating rooms, control of
      urological instruments has been taken away from a small cadre of dedicated
      urology nurses, and instead is delegated to a central sterilization department or
      is even outsourced, leading to an increased rate of instrument misplacement or
      breakage. Disposable kits are useful, but may not be stocked at all facilities.
      Hence, the tools needed by the urologist to perform suprapubic cystostomy may not
      be readily available when they are needed. This reality was the impetus for the
      development of the following technique for suprapubic tube placement, which
      relies only upon ordinary instruments. METHODS: A simple method is described for
      placing a suprapubic catheter using a curved Van Buren sound, a cystoscope, and a
      minor surgical set. RESULTS: Not only is the operation is easy to do, but is also
      advantageous in that the catheter may be exchanged over a wire, if necessary,
      before the establishment of a suprapubic tract. The technique depends on the
      presence of an intact urethra; therefore, it is contraindicated in the setting of
      pelvic trauma. CONCLUSION: This suprapubic cystostomy method may be used either
      as a primary technique or as a back-up procedure if the urologist's preferred
      instrumentation is not available.

PMID- 29352986
TI  - Association of Androgen Deprivation Therapy and Thromboembolic Events: A
      Systematic Review and Meta-analysis.
AB  - OBJECTIVES: To investigate the association of androgen deprivation therapy (ADT)
      for prostate cancer with thromboembolic events. METHODS: PubMed, Web of Science,
      and Scopus were queried on April 5, 2017 for systematic review. Additionally, The
      World Health Organization International Trials Registry Platform was queried on
      June 23, 2017. Eligible studies reported thromboembolic events among individuals
      with prostate cancer exposed to ADT vs a lesser-exposed group. Five hundred sixty
      nine unique studies were identified with 65 undergoing full-text review. We
      utilized the Meta-analysis of Observational Studies in Epidemiology statement
      guidelines and the Cochrane Review Group's data extraction template. Study
      quality was evaluated by Newcastle-Ottawa Scale criteria. We conducted random
      effects meta-analyses to calculate summary statistic risk ratios and 95%
      confidence intervals. Heterogeneity was quantified using the I2 statistic. Small
      study effects were evaluated using Begg and Egger statistics. RESULTS: In 10
      studies "ADT without estrogen" increased the risk of thromboembolic events (risk
      ratio [RR] 1.43, 95% confidence interval [CI] 1.15-1.77, P = .001). In 9 studies
      estrogen therapy alone was associated with an increased risk of thromboembolic
      events (RR 3.72, 95% CI 1.78-7.80, P <.001). We found an increased risk of
      thromboembolic events from ADT use without estrogen when limited to localized
      disease (RR 1.10, 95% CI 1.05-1.16, P <.001). Heterogeneity was resolved in those
      studies examining localized disease. There was no evidence of small study
      effects. CONCLUSION: The currently available evidence suggests that ADT without
      estrogen is associated with an increased the risk of thromboembolic events.

PMID- 29352987
TI  - The interaction between XBP1 and eNOS contributes to endothelial cell migration.
AB  - The X-box binding protein 1 (XBP1) is a pivotal transcription factor in the
      endoplasmic reticulum stress response. Our previous studies have proven that XBP1
      is involved in vascular endothelial growth factor (VEGF)-mediated endothelial
      cell (EC) proliferation and angiogenesis. In this study, we used EC monolayer
      wound healing, tube formation and transwell migration models to explore the role
      of XBP1splicing in EC migration. We found that scratching on EC monolayer
      triggered XBP1splicing, which was attenuated by the presence of SU5416and
      LY294002, suggesting that VEGF signalling pathways may be involved. Over
      expression of the spliced XBP1 (XBP1s) via Ad-XBP1s gene transfer increased while
      knockdown of IRE1alphaor XBP1 by ShRNA lentivirus suppressed EC migration. Over
      expression of XBP1s up-regulated the nitric oxide synthase 3 (NOS3)mRNA through
      the 3'UTR-mediated stabilisation and increased eNOS protein translation. Further
      experiments demonstrated that miR-24 participated in the XBP1s-induced eNOSup
      regulation and EC migration. Further co-IP and immunofluorescence staining assays
      revealed that protein kinase B (Akt), eNOS andXBP1s form a complex, resulting in
      Akt and eNOS nucleus relocation. These results suggest that XBP1 splicing can
      regulate eNOS expression and cellular location, leading to EC migration and
      therefore contributing to wound healing and angiogenesis.

PMID- 29352988
TI  - STAT3 as a promising chemoresistance biomarker associated with the
      CD44+/high/CD24-/low/ALDH+ BCSCs-like subset of the triple-negative breast cancer
      (TNBC) cell line.
AB  - The cancer stem cell (CSC) concept is currently employed to explain the mechanism
      of multidrug resistance that is implicated in the reduced efficacy of many
      chemotherapeutic agents, consequently leading to metastatic spread and disease
      relapse. We searched for potential predictive markers of doxorubicin (DOX)
      resistance in breast cancer stem cells (BCSCs) of the BT-549 human triple
      negative breast cancer (TNBC) cell line classified as a claudin-low subtype. In
      this study, we show that BT-549 presents a BCSCs-like subset determined by a
      CD44+/high/CD24-/low/ALDH1+ phenotype. The CD44+/high/CD24-/low/ALDH+ BCSCs-like
      subset presented the downregulation of a majority of the genes analyzed (64
      genes), and only 3 genes were upregulated after DOX treatment. Among the
      upregulated genes, MAPK3, PRKCZ and STAT3, STAT3 presented a higher level of
      upregulation in the DOX-treated CD44+/high/CD24-/low/ALDH+ BCSCs-like subset. The
      identification of biomarkers that predict antitumor responses is at the top of
      cancer research priorities. STAT3 was highlighted as a molecular signature in the
      CD44+/high/CD24-/low/ALDH1+ BCSCs-like subset obtained from the TNBC BT-549 cell
      line related to DOX resistance. A majority of the evaluated genes in the EGF
      pathway appear to be not associated with DOX resistance, as observed in the
      CD44+/high/CD24-/low/ALDH1+ BCSCs-like subset.

PMID- 29352989
TI  - Detrusor Acontractility after Acute Spinal Cord Injury-Myth or Reality?
AB  - PURPOSE: We assessed urodynamic parameters within the first 40 days after spinal
      cord injury to investigate whether the detrusor is acontractile during the acute
      phase of spinal cord injury. MATERIALS AND METHODS: We performed a prospective
      cohort study in 54 patients with neurogenic lower urinary tract dysfunction due
      to acute spinal cord injury who underwent urodynamic investigation within the
      first 40 days after injury at a single university spinal cord injury center.
      RESULTS: Urodynamic investigation revealed an acontractile detrusor in only 20 of
      the 54 patients (37%) but unfavorable urodynamic parameters in 34 (63%). We found
      detrusor overactivity in 32 patients, detrusor-sphincter dyssynergia in 25,
      maximum storage detrusor pressure greater than 40 cm H2O in 17, vesicoureteral
      reflux in 3 and low bladder compliance (less than 20 ml/cm H2O) in 1. More than 1
      unfavorable urodynamic parameter per patient was possible. CONCLUSIONS: In
      contrast to the common notion of an acontractile detrusor during acute spinal
      cord injury, almost two-thirds of our patients showed unfavorable urodynamic
      parameters within the first 40 days after spinal cord injury. Considering that
      early treatment of neurogenic lower urinary tract dysfunction in patients with
      acute spinal cord injury might improve the long-term urological outcome,
      urodynamic investigation should be performed timely to optimize patient tailored
      therapy.

PMID- 29352990
TI  - Low socioeconomic condition and the risk of dengue fever: A direct relationship.
AB  - This study aimed to characterize the first dengue fever epidemic in Varzea
      Paulista, Sao Paulo, Brazil, and its spatial and spatio-temporal distribution in
      order to assess the association of socioeconomic factors with dengue occurrence.
      We used autochthonous dengue cases confirmed in a 2007 epidemic, the first
      reported in the city, available in the Information System on Diseases of
      Compulsory Declaration database. These cases where geocoded by address. We
      identified spatial and spatio-temporal clusters of high- and low-risk dengue
      areas using scan statistics. To access the risk of dengue occurrence and to
      evaluate its relationship with socioeconomic level we used a population-based
      case-control design. Firstly, we fitted a generalized additive model (GAM) to
      dengue cases and controls without considering the non-spatial covariates to
      estimate the odds ratios of the occurrence of the disease. The controls were
      drawn considering the spatial distribution of the household of the study area and
      represented the source population of the dengue cases. After that, we assessed
      the relationship between socioeconomic variables and dengue using the GAM and
      obtained the effect of these covariates in the occurrence of dengue adjusted by
      the spatial localization of the cases and controls. Cluster analysis and GAM
      indicated that northeastern area of Varzea Paulista was the most affected area
      during the epidemic. The study showed a positive relationship between low
      socioeconomic condition and increased risk of dengue. We studied the first dengue
      epidemic in a highly susceptible population at the beginning of the outbreak and
      therefore it may have allowed to identify an association between low
      socioeconomic conditions and increased risk of dengue. These results may be
      useful to predict the occurrence and to identify priority areas to develop
      control measures for dengue, and also for Zika and Chikungunya; diseases that
      recently reached Latin America, especially Brazil.

PMID- 29352991
TI  - Molecular monitoring of dihydrofolatereductase (dhfr) and
      dihydropteroatesynthetase (dhps) associated with sulfadoxine-pyrimethamine
      resistance in Plasmodium vivax isolates of Palawan, Philippines.
AB  - The emergence of drug-resistant Plasmodium vivax poses problems for malaria
      control and elimination in some parts of the world, especially in developing
      countries where individuals are routinely exposed to the infection. The aim of
      this study was to determine the single nucleotide polymorphisms (SNPs) in
      dihydropteroate synthase (pvdhps) and dihydrofolate reductase (pvdhfr) genes
      associated with sulfadoxine-pyrimethamine (SP) drug resistance among P. vivax
      isolates collected in Palawan, Philippines. Genetic polymorphisms of pvdhps and
      pvdhfr were analysed by nested PCR. Analysis at specific codons
      I13P33F57S58T61S117I173 associated with pyrimethamine resistance in the pvdhfr
      gene revealed that most of the samples (66/87, 75.9%) carried double mutation at
      positions I13P33F57R58T61N117I173, while only 18.4% (16/87) of the isolates
      carried the wild-type haplotype (I13P33F57S58T61S117I173). For the pvdhps gene,
      the codons involved in sulfadoxine resistance S382A383K512A553V585 were
      investigated. Single mutation at position S382G383K512A553V585 was most observed
      in 68.0% (68/100) of the samples, whereas wild-type haplotype was found in 26.0%
      (26/100) of samples. The pvdhps and pvdhfr combination
      S382A383K512A553V585/I13P33F57S58T61S117I173 (wild-type),
      S382G383K512A553V585/I13P33F57R58T61N117I173, and S382A383K512A553V585
      I13P33F57R58T61N117I173 were the most frequently observed combination haplotypes
      from the three study sites. The information on molecular markers associated with
      antifolate drug-resistance could help better understanding ofthe molecular
      epidemiology and situation of SP resistant P. vivax malaria in the country.
      Continuous surveillance of these genetic markers is necessary to monitor the
      evolution of SP resistance in the Philippines.

PMID- 29352992
TI  - Endobronchial Granular Tumor Excision With Bronchial Resection Inclusive of
      Second Carinoplasty.
AB  - Bronchial granular cell tumor is a rare tumor. A 39-year-old nonsmoking woman was
      admitted to our hospital with back pain. Chest computed tomography scan and
      bronchoscopy revealed a 10-mm endobronchial tumor arising from the membrane near
      the second carina. The tumor was excised inclusive of the right second carina
      that contained the extraluminally invaded endobronchial mass and was diagnosed as
      a granular cell tumor. The postoperative course was uneventful, and the patient
      was well without signs of recurrence for 3 years of follow-up.

PMID- 29352995
TI  - Assessing risk of bias in studies that evaluate health care interventions:
      recommendations in the misinformation age.
AB  - Methods to assess the risk of bias in a way that is reliable, reproducible. and
      transparent to readers, have evolved over time. Viswanathan et al. recently
      provided updated recommendations for assessing risk of bias in systematic reviews
      of health care interventions. We comment on their recommendations and discuss new
      tools in development that we, as co-convenors and coordinators of the Cochrane
      Bias Methods Group, are leading, which complement the methods recommended.

PMID- 29352996
TI  - Plasticity Molecule Reveals Interneuronal Alterations in Alzheimer's Disease.

PMID- 29352994
TI  - Topical drug delivery devices: A review.
AB  - For the treatment and prevention of ocular diseases, most patients are treated
      with conventional drug delivery formulations such as eye drops or ointments.
      However, eye drops and ointments suffer from low patient compliance and low
      effective drug concentration at the target site. Therefore, new medical devices
      are being explored to improve drug delivery to the eye. Over the years, various
      delivery devices have been developed including resorbable devices, oval- and ring
      shaped devices, rod-shaped devices, punctum plugs, contact lenses and corneal
      shields. Only a few devices (eg. Mydriasert(r), Ozurdex(r), Surodex(r),
      Iluvien(r), Lacrisert(r) and Retisert(r)) have made it to the market while others
      are being investigated in clinical trials. Altogether, there is a need for
      enhanced topical drug delivery. Only by working together (academia, industry and
      authorities) and by exploring parallel strategies (new drug delivery devices,
      enhanced drug formulations, better understanding of the pharmacokinetic
      properties), the therapeutic effect of drug treatments can be improved.

PMID- 29352993
TI  - Comparison of chorioretinal layers in rhesus macaques using spectral-domain
      optical coherence tomography and high-resolution histological sections.
AB  - Nonhuman primates are important preclinical models of retinal diseases because
      they uniquely possess a macula similar to humans. Ocular imaging technologies
      such as spectral-domain optical coherence tomography (SD-OCT) allow noninvasive,
      in vivo measurements of chorioretinal layers with near-histological resolution.
      However, the boundaries are based on differences in reflectivity, and detailed
      correlations with histological tissue layers have not been explored in rhesus
      macaques, which are widely used for biomedical research. Here, we compare the
      macular anatomy and thickness measurements of chorioretinal layers in rhesus
      macaque eyes using SD-OCT and high-resolution histological sections. Images were
      obtained from methylmethacrylate-embedded histological sections of 6 healthy
      adult rhesus macaques, and compared with SD-OCT images from 6 age-matched
      animals. Thicknesses of chorioretinal layers were measured across the central 3
      mm macular region using custom semi-automated or manual software segmentation,
      and compared between the two modalities. We found that histological sections
      provide better distinction between the ganglion cell layer (GCL) and inner
      plexiform layer (IPL) than SD-OCT imaging. The first hyperreflective band between
      the external limiting membrane (ELM) and retinal pigment epithelium (RPE) appears
      wider on SD-OCT than the junction between photoreceptor inner and outer segments
      seen on histology. SD-OCT poorly distinguishes Henle nerve fibers from the outer
      nuclear layer (ONL), while histology correctly identifies these fibers as part of
      the outer plexiform layer (OPL). Overall, the GCL, inner nuclear layer (INL), and
      OPL are significantly thicker on histology, especially at the fovea; while the
      ONL, choriocapillaris (CC), and outer choroid (OC) are thicker on SD-OCT. Our
      results show that both SD-OCT and high-resolution histological sections allow
      reliable measurements of chorioretinal layers in rhesus macaques, with distinct
      advantages for different sublayers. These findings demonstrate the effects of
      tissue processing on chorioretinal anatomy, and provide normative values for
      chorioretinal thickness measurements on SD-OCT for future studies of disease
      models in these nonhuman primates.

PMID- 29352997
TI  - Microglia and Neonatal Brain Injury.
AB  - Microglial cells are now recognized as the "gate-keepers" of healthy brain
      microenvironment with their disrupted functions adversely affecting neurovascular
      integrity, neuronal homeostasis, and network connectivity. The perception that
      these cells are purely toxic under neurodegenerative conditions has been
      challenged by a continuously increasing understanding of their complexity, the
      existence of a broad array of microglial phenotypes, and their ability to rapidly
      change in a context-dependent manner to attenuate or exacerbate injuries of
      different nature. Recent studies have demonstrated that microglial cells exert
      crucial physiological functions during embryonic and postnatal brain development,
      some of these functions being unique to particular stages of development, and
      extending far beyond sensing dangerous signals and serving as antigen presenting
      cells. In this focused review we cover the roles of microglial cells in
      regulating embryonic vasculogenesis, neurogenesis, and establishing network
      connectivity during postnatal brain development. We further discuss context
      dependent microglial contribution to neonatal brain injuries associated with
      prenatal and postnatal infection and inflammation, in relation to
      neurodevelopmental disorders, as well as perinatal hypoxia-ischemia and arterial
      focal stroke. We also emphasize microglial phenotypic diversity, notably at the
      ultrastructural level, and their sex-dependent influence on the pathophysiology
      of neurodevelopmental disorders.

PMID- 29352999
TI  - Aortic dysfunction along with subaortic ridge in a patient with neurofibromatosis
      type 1 and a history of midaortic syndrome.

PMID- 29352998
TI  - Two Weeks of Variable Stress Increases Gamma-H2AX Levels in the Mouse Bed Nucleus
      of the Stria Terminalis.
AB  - Recent reports demonstrate that DNA damage is induced, and rapidly repaired, in
      circuits activated by experience. Moreover, stress hormones are known to slow DNA
      repair, suggesting that prolonged stress may result in persistent DNA damage.
      Prolonged stress is known to negatively impact physical and mental health;
      however, DNA damage as a factor in stress pathology has only begun to be
      explored. Histone H2A-X phosphorylated at serine 139 (gammaH2AX) is a marker of
      DNA double-strand breaks (DSB), a type of damage that may lead to cell death if
      unrepaired. We hypothesized that a 14-day period of variable stress exposure
      sufficient to alter anxiety-like behavior in male C57BL/6J mice would produce an
      increase in gammaH2AX levels in the bed nucleus of the stria terminalis (BNST), a
      region implicated in anxiety and stress regulation. We observed that 14 days of
      variable stress, but not a single stress exposure, was associated with increased
      levels of gammaH2AX 24 h after termination of the stress paradigm. Further
      investigation found that phosphorylation levels of a pair of kinases associated
      with the DNA damage response, glycogen synthase kinase 3 beta (GSK3beta) and p38
      mitogen-activated protein kinase (MAPK) were also elevated following variable
      stress. Our results suggest that unrepaired DNA DSBs and/or repetitive attempted
      repair may represent an important component of the allostatic load that stress
      places on the brain.

PMID- 29353000
TI  - Transarterial embolization of a late common hepatic artery pseudoaneurysm
      secondary to Stanford type B aortic dissection treated with thoracic endograft.

PMID- 29353001
TI  - Membrane progesterone receptors beta and gamma have potential as prognostic
      biomarkers of endometrial cancer.
AB  - Endometrial cancer (EC) is one of the most common malignancies in women
      worldwide. EC is linked to chronic exposure to estrogens that is unopposed by
      protective effects of progesterone. Progesterone modulates gene expression via
      classical nuclear receptors, and has rapid effects via the less characterized
      membrane-bound progesterone receptors (mPRs) of the progestin and adipoQ receptor
      (PAQR) family. The presence of mPRs in EC has not been investigated to date. The
      aims of this study were to examine PAQR7, PAQR8 and PAQR5, which encode for
      mPRalpha, mPRbeta and mPRgamma, respectively, for their expression and
      localization in EC tissue and adjacent control endometrium. Our results reveal
      decreased expression of PAQR7 and PAQR8, and unaltered expression of PAQR5 in EC
      versus control tissue. Expression of PAQR5 was decreased in EC with higher FIGO
      stage versus stage IA. Immunohistochemistry revealed lower levels of mPRalpha and
      mPRbeta, but higher levels of mPRgamma, in EC versus control tissue. There was
      greater decrease in mPRbeta levels in tumors with lymphovascular invasion. The
      analysis of the expression data associates higher PAQR5 mRNA and mPRbeta protein
      levels with favorable patient prognosis. Immunohistochemistry showed diverse
      localizations of mPRs in control and cancer endometrium. In control endometrium,
      mPRalpha and mPRbeta were localized mostly at the cell membranes, while mPRgamma
      was localized in the cytoplasm and/or nucleus. In cancer endometrium, mPRalpha
      and mPRbeta were detected at the cell membrane or in the cytoplasm, or both,
      while mPRgamma was only localized in the cytoplasm. Taken together, these results
      imply that mPRs are involved in EC pathogenesis through effects on the
      development or progression of cancer. The potential role of mPRbeta and mPRgamma
      as prognostic biomarkers needs to be further assessed on a larger number of
      samples.

PMID- 29353002
TI  - Telfairia occidentalis Hook.f. - associated haematopoietic effect is mediated by
      cytokines but independent of testosterone: A preliminary report.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Telfairia occidentalis Hook.f. (TO) is popular in
      Nigeria for the ethnopharmacological use of its leaves to improve haematological
      parameters in normal and anaemic subjects. Cytokines are well-known to regulate
      haematopoiesis. However, their involvement in TO-associated haematopoietic effect
      is not known and necessitated this study. MATERIALS AND METHODS: Twenty-five (25)
      male rats were randomly divided into 3 oral treatment groups as follows: Group 1
      (control, n=5) received 0.2 ml/kg normal saline for 14 days. Groups 2 and 3 (n=
      10 each) were subdivided into 2 (n=5) and received 100 mg/kg and 200 mg/kg of
      aqueous extract of TO respectively for 7 or 14 days. RESULTS: TO had dose- and
      duration-dependent effects on the estimated parameters. Both doses of TO
      increased the RBC, WBC and erythropoietin concentrations at 14 but not 7 days.
      Moreover, its 100 mg/kg increased haemoglobin, neutrophil, and interleukin-3
      concentrations at 7 days, while 200 mg/kg increased PCV and neutrophils at 14
      days, lymphocytes at 7 days, and haemoglobin at both durations. CONCLUSION: The
      haematopoietic effect of TO might be partly mediated by cytokines (interleukin-3
      and erythropoietin) but independent of testosterone.

PMID- 29353003
TI  - Urine and plasma metabolomics study on potential hepatoxic biomarkers
      identification in rats induced by Gynura segetum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Gynura segetum (GS) is an herbal medicine
      containing Pyrrolizidine Alkaloids (PAs) that causes hepatic sinusoidal
      obstruction syndrome (HSOS). AIM OF THE STUDY: To discover potential biomarkers
      and metabolic mechanisms involved in the hepatotoxicity induced by GS. METHODS:
      SD rats were randomly divided into 4 groups including Saline, the decoction of GS
      high, medium and low dosage at dosages of 3.75g * kg-1, 7.5g * kg-1 and 15g * kg
      1. A metabolomics approach using Ultraperformance Liquid Chromatography 
      Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) was developed to
      perform the plasma and urinary metabolic profiling analysis, and identified
      differential metabolites by comparing the saline control group and decoction of
      GS groups. RESULTS: The herbal was presented dosage-dependent led to
      ingravescence of hepatotoxicity after the rats were consecutively given with the
      decoction of GS at varied dosages. A total of 18 differential metabolites of
      decoction of GS-induced hepatotoxicity were identified, while 10 of them
      including arginine, proline, glutamate, creatine, valine, linoleic acid,
      arachidonic acid, sphinganine, phytosphingosine, and citric acid could be
      discovered in urine and plasma, and primarily involved in Amino acid metabolism,
      Lipids metabolism and Energy metabolism. CONCLUSIONS: The results suggested that
      the differential metabolites of arginine, creatine, valine, glutamine and citric
      acid were verified as potential markers of GS-induced hepatotoxicity via the
      regulation of multiple metabolic pathways primarily involving in Amino acids
      metabolism and Energy metabolism.

PMID- 29353004
TI  - Leishmania tropica isolates from non-healed and healed patients in Iran: A
      molecular typing and phylogenetic analysis.
AB  - The precise identification of the parasite species causing leishmaniasis is
      essential for selecting proper treatment modality. The present study aims to
      compare the nucleotide variations of the ITS1, 7SL RNA, and Hsp70 sequences
      between non-healed and healed anthroponotic cutaneous leishmaniasis (ACL)
      patients in major foci in Iran. A case-control study was carried out from
      September 2015 to October 2016 in the cities of Kerman and Bam, in the southeast
      of Iran. Randomly selected skin-scraping lesions of 40 patients (20 non-healed
      and 20 healed) were examined and the organisms were grown in a culture medium.
      Promastigotes were collected by centrifugation and kept for further molecular
      examinations. The extracted DNA was amplified and sequenced. After global
      sequence alignment with BioEdit software, maximum likelihood phylogenetic
      analysis was performed in PhyML for typing of Leishmania isolates. Nucleotide
      composition of each genetic region was also compared between non-healed and
      healed patients. Our results showed that all isolates belonged to the Leishmania
      tropica complex, with their genetic composition in the ITS1 region being
      different among non-healed and healed patients. 7SL RNA and Hsp70 regions were
      genetically identical between both groups. Variability in nucleotide patterns
      observed between both groups in the ITS1 region may serve to encourage future
      research on the function of these polymorphisms and may improve our understanding
      of the role of parasite genome properties on patients' response to Leishmania
      treatment. Our results also do not support future use of 7SL RNA and Hsp70
      regions of the parasite for comparative genomic analyses.

PMID- 29353005
TI  - Cryptotanshinone inhibits prostaglandin E2 production and COX-2 expression via
      suppression of TLR4/NF-kappaB signaling pathway in LPS-stimulated Caco-2 cells.
AB  - Crytotanshinone (CTN), one of the main constituents of Salvia miltiorrhiza, has
      been known to exhibit antioxdative, anti-inflammatory and other important
      therapeutic activities. The aim of this study was to evaluate the effect of CTN
      on prostaglandin E2 and COX-2 production in LPS-stimulated human intestinal cells
      (Caco-2 cells). Caco-2 cells were stimulated with LPS in the presence or absence
      of CTN. The production of prostaglandin E2 (PGE2) was detected by ELISA. The
      expression of COX-2 was detected by qRT-PCR and Western blot. The extent of
      phosphorylation of IkappaB-alpha, NF-kappaB p65 and the expression of TLR4 were
      detected by western blot. The results showed that CTN dose-dependently inhibited
      the expression of COX-2 both in mRNA and protein levels, resulting in a decreased
      production of PGE2. We also found that CTN suppressed LPS-induced NF-kappaB
      activation and IkappaBalpha degradation. Furthermore, CTN inhibited the
      expression of TLR4 up-regulated by LPS. These results suggest that CTN exerts an
      anti-inflammatory property by inhibiting TLR4/NF-kappaB signaling pathway and the
      release of pro-inflammatory mediators. These findings suggest that CTN may be a
      therapeutic agent against intestinal inflammatory diseases.

PMID- 29353007
TI  - Nitric oxide suppresses aluminum-induced programmed cell death in peanut (Arachis
      hypoganea L.) root tips by improving mitochondrial physiological properties.
AB  - Aluminum (Al) stress alters nitric oxide (NO) and induces programmed cell death
      (PCD) in plants. Recent study has shown that NO inhibits Al-induced PCD. However,
      the mechanism of NO inhibiting Al-induced PCD has not been revealed yet. Here, we
      investigated the behavior of mitochondria during Al-induced PCD suppressed by NO
      in peanut. Seedlings of peanut was grown hydroponically in a controllable growth
      room. The mitochondrial physiological parameters were determined
      spectrophotometrically. The expression of AhANT and AhHsp70 was determined by
      quantitative RT-PCR. Al-induced cell death rapidly in peanut root tips is
      mitochondria-dependent PCD. There was a significantly negative relationship
      between PCD and mitochondrial NO/H2O2 level. Compared with Al treatment alone,
      the addition of NO donor sodium nitroprusside (SNP) increased the ratio of
      NO/H2O2, down-regulated AhANT expression and inhibited the opening of
      mitochondrial permeability transition pore (MPTP), up-regulated AhHsp70
      expression and increased mitochondrial inner membrane potential (DeltaPsim),
      reduced cytochrome c (Cyt c) release from mitochondria and caspase 3-like
      protease activity, while the effect of NO specific scavenger cPTIO supplement was
      opposite. NO suppresses Al-induce PCD in peanut root tips by improving
      mitochondrial physiological properties.

PMID- 29353006
TI  - Comparing the portion size effect in women with and without extended training in
      portion control: A follow-up to the Portion-Control Strategies Trial.
AB  - Following a 1-year randomized controlled trial that tested how weight loss was
      influenced by different targeted strategies for managing food portions, we
      evaluated whether the effect of portion size on intake in a controlled setting
      was attenuated in trained participants compared to untrained controls. Subjects
      were 3 groups of women: 39 participants with overweight and obesity from the
      Portion-Control Strategies Trial, 34 controls with overweight and obesity, and 29
      controls with normal weight. In a crossover design, on 4 different occasions
      subjects were served a meal consisting of 7 foods that differed in energy density
      (ED). Across the meals, all foods were varied in portion size (100%, 125%, 150%,
      or 175% of baseline). The results showed that serving larger portions increased
      the weight and energy of food consumed at the meal (P < .0001), and this effect
      did not differ across groups. Increasing portions by 75% increased food intake by
      a mean (+/-SEM) of 111 +/- 10 g (27%) and increased energy intake by 126 +/- 14
      kcal (25%). Across all meals, however, trained participants had lower energy
      intake (506 +/- 15 vs. 601 +/- 12 kcal, P = .006) and lower meal ED (1.09 +/-
      0.02 vs. 1.27 +/- 0.02 kcal/g; P = .003) than controls, whose intake did not
      differ by weight status. The lower energy intake of trained participants was
      attributable to consuming meals with a greater proportion of lower-ED foods than
      controls. These results further demonstrate the robust nature of the portion size
      effect and reinforce that reducing meal ED is an effective way to moderate energy
      intake in the presence of large portions.

PMID- 29353008
TI  - Isolated Ovarian Endometrioma: A History Between Myth and Reality.
AB  - STUDY OBJECTIVE: To assess the association between ovarian endometriomas
      detectable at transvaginal ultrasound (TVS) and other specific extraovarian
      lesions including adhesions, deep infiltrating endometriosis (DIE), and
      adenomyosis. DESIGN: Retrospective observational study (Canadian Task Force
      classification II-2). SETTING: Two university hospitals. PATIENTS: Two hundred
      fifty-five symptomatic women with at least 1 ovarian endometrioma found on
      ultrasound after presentation with pain or irregular menstruation. INTERVENTIONS:
      Patients underwent TVS followed by either medical or surgical treatment.
      MEASUREMENTS AND MAIN RESULTS: Two hundred fifty-five women, aged 20 to 40 years,
      underwent TVS and were found to have at least 1 endometrioma with a diameter > 20
      mm. Associated sonographic signs of pelvic endometriosis (adhesions, DIE, and
      adenomyosis) were recorded, and a subgroup of patients (n = 50) underwent
      laparoscopic surgery within 3 months of TVS. Mean endometrioma diameter was 40.0
      +/- 18.1 mm, and bilateral endometriomas were observed in 65 patients (25.5%).
      TVS showed posterior rectal DIE in 55 patients (21.5%) and a thickening of at
      least 1 uterosacral ligament in 93 patients (36.4%). One hundred eighty-six
      patients (73%) had adhesions, and 134 patients (53%) showed signs of myometrial
      adenomyosis on TVS. Thirty-eight patients (15%) exhibited only a single isolated
      endometrioma with a mobile ovary and no other signs of pelvic
      endometriosis/adenomyosis at TVS. CONCLUSION: Ovarian endometriomas are
      indicators for pelvic endometriosis and are rarely isolated. Particularly, left
      endometriomas were found to be associated with rectal DIE and left uterosacral
      ligament localization and bilateral endometriomas correlated with adhesions and
      pouch of Douglas obliteration, whereas no correlation was found between
      endometrioma size and DIE. Determining appropriate management, whether clinical
      or surgical, is critical for ovarian endometriomas and concomitant adhesions,
      endometriosis, and adenomyosis in patients desiring future fertility.

PMID- 29353009
TI  - A Rare Case of Cutaneous Metastases Secondary to Hepatocellular Carcinoma.

PMID- 29353010
TI  - Modulation of immune responses by Plasmodium falciparum infection in asymptomatic
      children living in the endemic region of Mbita, western Kenya.
AB  - Individuals living in malaria endemic areas become clinically immune after
      multiple re-infections over time and remain infected without apparent symptoms.
      However, it is unclear why a long period is required to gain clinical immunity to
      malaria, and how such immunity is maintained. Although malaria infection is
      reported to induce inhibition of immune responses, studies on asymptomatic
      individuals living in endemic regions of malaria are relatively scarce. We
      conducted a cross-sectional study of immune responses in asymptomatic school
      children aged 4-16years living in an area where Plasmodium falciparum and
      Schistosoma mansoni infections are co-endemic in Kenya. Peripheral blood
      mononuclear cells were subjected to flow cytometric analysis and cultured to
      determine proliferative responses and cytokine production. The proportions of
      cellular subsets in children positive for P. falciparum infection at the level of
      microscopy were comparable to the negative children, except for a reduction in
      central memory-phenotype CD8+ T cells and natural killer cells. In functional
      studies, the production of cytokines by peripheral blood mononuclear cells in
      response to P. falciparum crude antigens exhibited strong heterogeneity among
      children. In addition, production of IL-2 in response to anti-CD3 and anti-CD28
      monoclonal antibodies was significantly reduced in P. falciparum-positive
      children as compared to -negative children, suggesting a state of
      unresponsiveness. These data suggest that the quality of T cell immune responses
      is heterogeneous among asymptomatic children living in the endemic region of P.
      falciparum, and that the responses are generally suppressed by active infection
      with Plasmodium parasites.

PMID- 29353011
TI  - Genetic diversity and phylogenetic relations of salmon trematode Nanophyetus
      japonensis.
AB  - Nanophyetiasis is the severe zoonotic disease caused by parasitic worms from the
      genus Nanophyetus. Humans and carnivorous animals become infected when they
      ingest raw fish containing metacercariae, especially Pacific salmonids.
      Nanophyetiasis is detected in limited geographical areas which include the
      coastal regions of the North Pacific: the United States of America, Russian
      Federation and Japan. Despite the epidemiological significance, Nanophyetus
      species have not been well studied genetically. In this research, we for the
      first time explored genetic diversity of Nanophyetus japonensis from Japan in
      comparison with those of related species, N. salmincola from North America and N.
      schikhobalowi from the Russian Far East, based on sequence variation in the
      nuclear ribosomal gene family (18S, ITS1-5.8S-ITS2 and 28S) and mitochondrial
      nad1 gene, encoding subunit I of the respiratory chain NADH dehydrogenase. The
      results confirmed the independent species status for the compared flukes,
      demonstrated a greater genetic similarity of Asian species between themselves
      than each of them with the North American one, suggesting that N. japonensis and
      N. schikhobalowi are close sister species, and also revealed discrepancy between
      the levels of morphological and genetic differentiation.

PMID- 29353013
TI  - Bottom-up gamma maintenance in various disorders.
AB  - Maintained gamma band activity is a key element of higher brain function,
      participating in perception, executive function, and memory. The pedunculopontine
      nucleus (PPN), as part of the reticular activating system (RAS), is a major
      source of the "bottom-up" flow of gamma activity to higher regions. However,
      interruption of gamma band activity is associated with a number of neurological
      and psychiatric disorders. This review will focus on the role of the PPN in
      activating higher regions to induce arousal and descending pathways to modulate
      posture and locomotion. As such, PPN deep brain stimulation (DBS) can not only
      help regulate arousal and stepping, but continuous application may help maintain
      necessary levels of gamma band activity for a host of other brain processes. We
      will explore the potential future applications of PPN DBS for a number of
      disorders that are characterized by disturbances in gamma band maintenance.

PMID- 29353012
TI  - Fabrication of poly(ethylene glycol)-coated mesoporous nanocomposite ZnO@Fe2O3
      for methotrexate delivery: An integrated nanoplatform for dual-mode cancer
      therapy.
AB  - Although chemotherapy is an effective strategy for treatment of tumor cells, the
      non-specific distribution of chemotherapy drugs and their poor aqueous solubility
      result in impaired treatment and cause serious side effects in patients. In this
      study, mesoporous ZnO@Fe2O3 nanocomposite was fabricated and used as a platform
      for drug delivery. ZnO@Fe2O3 nanocomposite showed a high capacity for the
      adsorption of chemotherapy drug, methotrexate (MTX). Drug-loaded nanoparticle was
      coated with poly(ethylene glycol) (PEG), leading to the enhanced colloidal
      stability and good cytocompatibility. In order to improve tumor selective
      targeting of PEG-coated nanoparticles, it was also decorated with folic acid.
      Fabricated drug delivery system (F-P-M-ZnO@Fe2O3) was characterized by FT-IR,
      TGA, zeta potential, and UV-Visible spectroscopy. F-P-M-ZnO@Fe2O3 nanoparticles
      showed spatio-temporal drug release which was precisely controlled by pH and UVA
      light. In vitro biological studies on breast cancer cell lines (MCF-7 and T47D
      cells) revealed that F-P-M-ZnO@Fe2O3 nanoparticles can be internalized by
      clathrin-mediated endocytosis in energy-dependent and folate receptor-dependent
      manner. Cytotoxicity experiments showed that the treatment of tumor cells with
      both F-P-M-ZnO@Fe2O3 nanoparticle and UV irradiation causes better synergistic
      effect in inducing cellular apoptosis than the free drug and UV irradiation
      alone. Induction of apoptosis occurred following the mitochondrial membrane
      disruption and caspase activation. Moreover, F-P-M-ZnO@Fe2O3 did not affect
      normal cells, indicating the selective cytotoxic effect of fabricated nanosystem.
      From these data, F-P-M-ZnO@Fe2O3 is a dual-responsive nanoplatform which could be
      considered as an appropriate candidate for targeted chemo-phototherapy in cancer.

PMID- 29353014
TI  - Neuroprotective effect of morin on lead acetate- induced apoptosis by preventing
      cytochrome c translocation via regulation of Bax/Bcl-2 ratio.
AB  - Lead (Pb) intoxication is a prevalent type of environmental toxicity as well as
      minimal amount of lead exposure is liable for neurobehavioral or perhaps
      intelligence defects. The present study was undertaken to investigate the
      beneficial effects of morin in protecting the lead acetate (PbAc)-induced
      oxidative stress in rat brain. PbAc intoxication resulted in motor deficit,
      memory impairment and oxidative stress Further, PbAc administration alters
      Bax/Bcl-2 expression thereby increases cytochrome c release from the
      mitochondria. Treatment with morin at a dose of 40 mg/kg b.wt. significantly
      restored back the abnormal changes that were noticed in PbAc intoxicated rats.
      Histopathological sections of cortex, cerebellum and hippocampus showed the
      extent of neuronal loss in PbAc induced rats and its restoration upon
      administration of morin. These outcomes imply that morin might be employed
      therapeutically to chelate toxic metals like Pb, thus possibly lowering PbAc
      induced neurotoxicity and tissue damage.

PMID- 29353015
TI  - Proteomic and functional variation within black snake venoms (Elapidae:
      Pseudechis).
AB  - Pseudechis (black snakes) is an Australasian elapid snake genus that inhabits
      much of mainland Australia, with two representatives confined to Papua New
      Guinea. The present study is the first to analyse the venom of all 9 described
      Pseudechis species (plus one undescribed species) to investigate the evolution of
      venom composition and functional activity. Proteomic results demonstrated that
      the typical Pseudechis venom profile is dominated by phospholipase A2 toxins.
      Strong cytotoxicity was the dominant function for most species. P. porphyriacus,
      the most basal member of the genus, also exhibited the most divergent venom
      composition, being the only species with appreciable amounts of procoagulant
      toxins. The relatively high presence of factor Xa recovered in P. porphyriacus
      venom may be related to a predominantly amphibian diet. Results of this study
      provide important insights to guide future ecological and toxinological
      investigations.

PMID- 29353017
TI  - pH-triggered surface charge-reversal nanoparticles alleviate experimental murine
      colitis via selective accumulation in inflamed colon regions.
AB  - In this study, we developed pH-triggered surface charge-reversal lipid
      nanoparticles (LNPs), loaded with budesonide, which could precisely deliver the
      drug to inflamed colon segments for the treatment of ulcerative colitis.
      Polyethyleneimine (PEI) was used to render LNPs cationic (PEI-LNPs), and
      Eudragit(r) S100 (ES) was coated on PEI-LNPs to obtain pH-triggered charge
      reversal LNPs (ES-PEI-LNPs). ES coating avoided a burst drug release under acidic
      conditions mimicking the stomach and early small intestine environments and
      showed a sustained release in the colon. The surface charge of ES-PEI-LNPs
      switched from negative to positive under colonic conditions owing to pH-triggered
      removal of the ES coating. Bioimaging of the mouse gastrointestinal tract and
      confocal analysis of colon tissues revealed that ES-PEI-LNPs selectively
      accumulated in an inflamed colon. Furthermore, ES-PEI-LNPs mitigated experimental
      colitis in mice. These results suggest that the pH-triggered charge-reversal LNPs
      could be a promising drug carrier for ulcerative colitis therapy and other colon
      targeted treatments.

PMID- 29353016
TI  - Pyrosequencing analysis of methylation levels of clock genes in leukocytes from
      Parkinson's disease patients.
AB  - DNA methylation of neuronal PAS domain protein 2 (NPAS2) and cryptochrome
      circadian clock 1 (CRY1) promoters may be associated with Parkinson's disease
      (PD). However, there is no simple and cost-effective method to quantify DNA
      methylation in these regions. Additionally, it is not clear whether DNA
      methylation of NPAS2 and CRY1 promoters is altered in peripheral blood of PD
      patients, especially newly diagnosed drug-naive PD patients, and thus can be used
      as a PD biomarker. In the present study, we utilized bisulfite pyrosequencing
      assays to examine DNA methylation levels of six CpG sites in the NPAS2 promoter
      and five CpG sites in the CRY1 promoter. We compared DNA methylation levels at
      these sites in leukocytes from 80 medicated PD patients, 30 drug-naive PD
      patients, and 80 healthy controls. Our results indicate that NPAS2
      hypomethylation occurs at the early stage of PD and is a moderate biomarker for
      distinguishing PD patients from healthy subjects.

PMID- 29353018
TI  - Nebulization effects on structural stability of bacteriophage PEV 44.
AB  - Reduced infectivity of phage due to the nebulization process has been reported
      previously, but no visual evidence on structural change upon nebulization has
      been established, or whether these structural changes can be attributed to the
      titer reduction. In this study, transmission electron microscopy (TEM) was
      employed to assess the impact of three different types of nebulizers, air-jet,
      vibrating-mesh and static-mesh nebulizers, on the structural stability of a
      Myoviridae phage, PEV44, active against Pseudomonas aeruginosa. The morphology of
      the phage in the nebulized samples was categorized into two groups: "whole" (the
      capsid and tail held together) and "broken" (the capsid separated from the tail)
      phages. The "whole" phage group was further divided into three sub-groups: (1)
      intact, (2) contracted tail and (3) empty capsid. The starting stock suspension
      was found to contain considerable portions of "broken" phages (35.5 +/- 6.7%),
      "whole" phages with contracted tails (9.9 +/- 5.4%) and empty capsids (19.3 +/-
      8.9%). The fraction of "broken" phages was significantly increased after
      nebulization, with the air-jet nebulizer (83%) being more pronounced than the
      mesh type nebulizers (50-60%). While the amount of intact phages (2-10%) and
      whole phages with contracted tails (0-3%) were significantly decreased, the
      proportion of phages with empty capsids (15-36%) were not significantly
      different. Phages with broken features obtained by TEM quantification were 92.9
      +/- 3.2%, 74.8 +/- 10.4% and 71.2 +/- 11.0% for the jet, vibrating-mesh and
      static-mesh nebulizers, respectively. These results were found to be comparable
      with the titer loss obtained by the conventional plaque assay results. The in
      vitro aerosol performance and viable phage delivery of the three nebulizers was
      also assessed. The Omron nebulizer achieved a significantly higher viable
      respirable fraction (VRF) than the SideStream and Aeroneb Go (15.1 +/- 5.8%, 2.4
      +/- 2.0%, 4.1 +/- 2.7% respectively). In conclusion, this study identified
      various changes in the phage structure and viability of phage from different
      types of nebulizers. Understanding these effects and the phage tolerance to
      nebulization stresses can potentially improve our choice of the delivery method
      for inhaled phage therapy.

PMID- 29353019
TI  - Induction by innate defence regulator peptide 1018 of pro-angiogenic molecules
      and endothelial cell migration in a high glucose environment.
AB  - Synthetic innate defence regulator (IDR) peptides such as IDR-1018 modulate
      immunity to promote key protective functions including chemotaxis, wound healing,
      and anti-infective activity, while suppressing pro-inflammatory responses to non
      pathological levels. Here we demonstrated that IDR-1018 induced, by up to 75
      fold, pro-angiogenic VEGF-165 in keratinocytes but suppressed this isoform in
      endothelial cells. It also induced early angiogenin and prolonged anti
      inflammatory TGFbeta expression on endothelial cells, while suppressing early pro
      inflammatory IL-1beta expression levels. IDR-1018 also down-regulated the hypoxia
      induced transcription factor HIF-1alpha in both keratinocytes and endothelial
      cells. Consistent with these data, in an in vitro wound healing scratch assay,
      IDR-1018 induced migration of endothelial cells under conditions of hypoxia while
      in epithelial cells migration increased only under conditions of normoxia.

PMID- 29353020
TI  - Ultrasound improves antimicrobial effect of sodium dichloroisocyanurate to reduce
      Salmonella Typhimurium on purple cabbage.
AB  - The consumer's interest in ready-to-eat, fast-ready, nutritious and fresh foods
      is a major challenge for the food industry. Thus, studies on new sanitization
      methods are relevant. The effect of Sodium Hypochlorite (SH), Benzalkonium
      Chloride (BC), and Sodium Dichloroisocyanurate (SD) isolated or combined with
      Ultrasound (US) in purple cabbage quality over 7 days of storage at 8 +/- 1 
      degrees C was evaluated. The natural microbiota (mesophilic aerobic bacteria,
      lactic acid bacteria and coliforms), intentionally inoculated Salmonella
      Typhimurium, physicochemical quality (anthocyanins, pH, total titratable acidity,
      instrumental color and mass loss) and sensorial quality (multiple comparison test
      and visual sensory acceptance) were analyzed. The best treatments for natural
      microbiota reduction were BC and US + BC, which in general reduced between 1.9
      and 3.2 log cfu/g. US improved (p < .05) the effect of SD reducing almost 4 log
      cycles in the population of S. Typhimurium adhered to cabbage. The treatments
      with benzalkonium chloride resulted in important physicochemical changes in
      cabbage. The treatments SD and US + SD did not alter the physicochemical and
      sensorial characteristics of purple cabbage. Therefore, ultrasound combined with
      sodium dichloroisocyanurate is a promising alternative for the reduction of
      microbiological contaminants of purple cabbage without physicochemical, sensory
      and anthocyanin content loss.

PMID- 29353021
TI  - Phosphoproteomics unveils stable energy supply as key to flooding tolerance in
      Kandelia candel.
AB  - : The mangrove Kandelia candel (L.) Druce experiences daily flooding cycles. To
      explore the molecular mechanism underlying the physiological adaptation of K.
      candel to flooding, the potential role of protein phosphorylation in flooding
      responses was investigated by a large-scale quantitative phosphoproteomic
      analysis using isobaric tag for relative and absolute quantitation. Total 2141
      unique phosphopeptides and 2603 non-redundant phosphorylation sites were
      identified from 1516 phosphoproteins in K. candel leaves. In addition to known
      phosphorylation motifs, three new motifs [GSP], [GxxSP] and [RSxS] were
      discovered. The phosphorylation levels of 96 differentially expressed
      phosphoproteins, including those involved in pyruvate metabolism and energy
      production, were identified in response to flooding. The physiological parameters
      and transcriptional levels relevant to flooding responses including
      photosynthesis, pyruvate metabolism, and ROS production were investigated and all
      were found to be robust under flooding conditions. The consistent results of the
      phosphoproteomic, physiological analyses and transcriptional levels reinforce
      each other to demonstrate that K. candel adapts to flooding through maintaining
      sufficient photosynthesis activities, achieving effective anaerobic respiration
      and increasing pentose phosphate pathway flux. Protein phosphorylation is likely
      to play a major role in the regulation of these pathways which together
      contribute to stable energy supply that enhances flooding tolerance in K. candel.
      BIOLOGICAL SIGNIFICANCE: Flooding stress is one of the major environmental
      stresses. The woody mangrove Kandelia candel experiences daily flooding cycles in
      its natural habitat. Protein phosphorylation is a crucial regulatory mechanism in
      plants' responses to both biotic and abiotic stresses. To analyze phosphorylation
      levels in critical enzymes involved in key metabolic pathways, we employed
      phosphoproteomic approach to dissect the adaptive mechanism of K. candel to
      flooding conditions. To our knowledge, this is the first large-scale quantitative
      phosphoproteomic analyses of K. candel's flooding responses. Multiplex iTRAQ
      based quantitative proteomic and Nano-LC-MS/MS methods were used to construct the
      phosphorproteome. Our results indicate that K. candel is able to acquire stable
      energy supply under flooding by maintaining sufficient photosynthesis activities,
      enhancing effective anaerobic respiration and increasing pentose phosphate
      pathway (PPP) flux. The protein phosphorylation found in photosynthesis,
      anaerobic respiration and PPP is likely to play important roles in the flooding
      tolerance of K. candel.

PMID- 29353023
TI  - Diaphragm Excursion-Time Index: A New Parameter Using Ultrasonography to Predict
      Extubation Outcome.
AB  - BACKGROUND: The diaphragmatic response to increased mechanical load following
      withdrawal of mechanical ventilation is critical in determining the outcome of
      extubation. Using ultrasonography, we aimed to evaluate the performance of the
      excursion-time (E-T) index-a product of diaphragm excursion and inspiratory time,
      to predict the outcome of extubation. METHODS: Right hemidiaphragm excursion,
      inspiratory time, and E-T index were measured by ultrasonography during
      mechanical ventilation: (1) on assist-control (A/C) mode during consistent
      patient-triggered ventilation, (2) following 30 min during a spontaneous
      breathing trial (SBT), and (3) between 4 and 24 h following extubation. These
      measurements were correlated with the outcome of extubation. Patients in the
      "failure" group required reintubation or noninvasive ventilation within 48 h of
      extubation. RESULTS: Of the 73 patients studied, 20 patients failed extubation.
      During SBT, diaphragm excursion was 1.65 +/- 0.82 and 2.1 +/- 0.9 cm (P = .06),
      inspiratory time was 0.89 +/- 0.30 and 1.11 +/- 0.39 s (P = .03), and the E-T
      index was 1.64 +/- 1.19 and 2.42 +/- 1.55 cm-s (P < .03) in the "failure" and
      "success" groups, respectively. The mean change in E-T index between A/C and SBT
      was -3.9 +/- 57.8% in the failure group and 59.4 +/- 74.6% in the success group
      (P < .01). A decrease in diaphragmatic E-T index less than 3.8% between A/C and
      SBT had a sensitivity of 79.2% and a specificity of 75%, to predict successful
      extubation. CONCLUSIONS: Diaphragm E-T index measured during SBT may help predict
      the outcome of extubation. Maintenance or increase in diaphragm E-T index between
      A/C and SBT increases the likelihood of successful extubation.

PMID- 29353022
TI  - Using medical examiner case narratives to improve opioid overdose surveillance.
AB  - BACKGROUND: Current opioid overdose mortality surveillance methods do not capture
      the complexity of the overdose epidemic. Most rely on death certificates, which
      may underestimate both opioid analgesic and heroin deaths. Categorizing deaths
      using other characteristics from the death record including route of drug
      administration may provide useful information to design and evaluate overdose
      prevention interventions. METHODS: We reviewed California Electronic Death
      Reporting System records and San Francisco Office of the Chief Medical Examiner
      (OCME) toxicology reports and investigative case narratives for all unintentional
      opioid overdose deaths in San Francisco County from 2006 to 2012. We chose this
      time period because it encompassed a period of evolution in local opioid use
      patterns and expansion of overdose prevention efforts. We created a
      classification system for heroin-related and injection-related opioid overdose
      deaths and compared demographic, death scene, and toxicology characteristics
      among these groups. RESULTS: We identified 816 unintentional opioid overdose
      deaths. One hundred fifty-two (19%) were standard heroin deaths, as designated by
      the OCME or by the presence of 6-monoacetylmorphine. An "expanded" classification
      for heroin deaths incorporating information from toxicology reports and case
      narratives added 20 additional heroin deaths (13% increase), accounting for 21%
      of all opioid deaths. Two hundred five deaths (25%) were injection-related, 60%
      of which were attributed to heroin. A combined classification of expanded heroin
      and injection-related deaths accounted for 31% of opioid overdose deaths during
      this period. CONCLUSIONS: Using additional sources of information to classify
      opioid overdose cases resulted in a modest increase in the count of heroin
      overdose deaths but identified a substantial number of non-heroin injection
      related opioid analgesic deaths. Including the route of administration in the
      characterization of opioid overdose deaths can identify meaningful subgroups of
      opioid users to enhance surveillance efforts and inform targeted public health
      programming including overdose prevention programs.

PMID- 29353024
TI  - Outcomes and Mortality Prediction Model of Critically Ill Adults With Acute
      Respiratory Failure and Interstitial Lung Disease.
AB  - BACKGROUND: We aimed to examine short- and long-term mortality in a mixed
      population of patients with interstitial lung disease (ILD) with acute
      respiratory failure, and to identify those at lower vs higher risk of in-hospital
      death. METHODS: We conducted a single-center retrospective cohort study of 126
      consecutive adults with ILD admitted to an ICU for respiratory failure at a
      tertiary care hospital between 2010 and 2014 and who did not undergo lung
      transplantation during their hospitalization. We examined associations of ICU-day
      1 characteristics with in-hospital and 1-year mortality, using Poisson
      regression, and examined survival using Kaplan-Meier curves. We created a risk
      score for in-hospital mortality, using a model developed with penalized
      regression. RESULTS: In-hospital mortality was 66%, and 1-year mortality was 80%.
      Those with connective tissue disease-related ILD had better short-term and long
      term mortality compared with unclassifiable ILD (adjusted relative risk, 0.6; 95%
      CI, 0.3-0.9; and relative risk, 0.6; 95% CI, 0.4-0.9, respectively). Our
      prediction model includes male sex, interstitial pulmonary fibrosis diagnosis,
      use of invasive mechanical ventilation and/or extracorporeal life support, no
      ambulation within 24 h of ICU admission, BMI, and Simplified Acute Physiology
      Score-II. The optimism-corrected C-statistic was 0.73, and model calibration was
      excellent (P = .99). In-hospital mortality rates for the low-, moderate-, and
      high-risk groups were 33%, 65%, and 96%, respectively. CONCLUSIONS: We created a
      risk score that classifies patients with ILD with acute respiratory failure from
      low to high risk for in-hospital mortality. The score could aid providers in
      counseling these patients and their families.

PMID- 29353025
TI  - Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with
      moderate-to-severe atopic dermatitis inadequately controlled by conventional
      treatments: A randomized, double-blind, phase 2a trial.
AB  - BACKGROUND: Interleukin 22 promotes epidermal hyperplasia and inhibits skin
      barrier function. OBJECTIVE: Evaluate interleukin 22 blockade in adults with
      moderate-to-severe atopic dermatitis (AD). METHODS: We performed a randomized,
      double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy
      every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change
      in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end
      point. RESULTS: At 12 weeks, the mean declines in SCORAD for the entire study
      population were 13.8 +/- 2.7 in the fezakinumab arm and 8.0 +/- 3.1 in the
      placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD
      of >=50), SCORAD decline was significantly stronger in the drug-treated patients
      than placebo-treated patients at 12 weeks (21.6 +/- 3.8 vs 9.6 +/- 4.2, P = .029)
      and 20 weeks (27.4 +/- 3.9 vs 11.5 +/- 5.1, P = .010). At 12 weeks, improvements
      in body surface area involvement in the entire population were significantly
      stronger in the drug-treated than placebo-treated patients (12.4% +/- 2.4 vs 6.2%
      +/- 2.7; P = .009), and in the severe AD subset, the decline in Investigator
      Global Assessment was significantly higher in the drug-treated than placebo
      treated patients (0.7 +/- 0.2 vs 0.3 +/- 0.1; P = .034). All scores showed
      progressive improvements after last dosing (10 weeks) until end of study (20
      weeks). Common adverse events were upper respiratory tract infections.
      LIMITATIONS: The limited sample size and lack of assessment with Eczema Area and
      Severity Index and a pruritus numerical rating scale were limiting factors.
      Significance was primarily obtained in severe AD. CONCLUSION: Fezakinumab was
      well-tolerated, with sustained clinical improvements after last drug dosing.

PMID- 29353026
TI  - Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults
      with moderate-to-severe atopic dermatitis inadequately controlled by topical
      corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE).
AB  - BACKGROUND: Interleukin (IL)-13 plays a key role in type 2 inflammation and is an
      emerging pathogenic mediator in atopic dermatitis (AD). OBJECTIVE: We
      investigated the efficacy and safety of lebrikizumab, an IL-13 monoclonal
      antibody, as an add-on to topical corticosteroid (TCS) treatment. METHODS: A
      randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate
      to-severe AD were required to use TCS twice daily and then randomized (1:1:1:1)
      to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab
      125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a
      2-week TCS run-in. The primary endpoint was percentage of patients achieving
      Eczema Area and Severity Index (EASI)-50 at week 12. RESULTS: In total, 209
      patients received the study drug. At week 12, significantly more patients
      achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P = .026) than
      placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab
      showed no statistically significant improvements in EASI-50 compared with
      placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs
      66.0% placebo) and mostly mild or moderate. LIMITATIONS: Protocol-mandated twice
      daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a
      monotherapy. The short study duration did not enable long-term efficacy or safety
      evaluations. CONCLUSION: When combined with TCS, lebrikizumab 125 mg taken every
      4 weeks led to a significant improvement and was well tolerated in patients with
      moderate-to-severe AD.

PMID- 29353027
TI  - Estrogen Receptor-alpha is Involved in Tamoxifen Neuroprotective Effects in a
      Traumatic Brain Injury Male Rat Model.
AB  - OBJECTIVE: To determine the neuroprotective mechanisms of tamoxifen (TMX) during
      traumatic brain injury (TBI), especially the effects on estrogen receptor-alpha
      (ERalpha) expression, as well as neuroinflammatory associations. MATERIALS AND
      METHODS: Anesthetized male Sprague-Dawley rats were divided into 4 groups: sham
      operated controls, sham-operated controls given TMX (1 mg/kg/per day) for 3 days,
      those given a vehicle solution immediately after TBI, and those given TMX (1
      mg/kg/per day) for 3 days. The functional outcome was evaluated by assessments of
      body weight and proprioception. The total ERalpha expression in the cortex also
      was investigated by Western blotting, and ERalpha expression in neurons,
      microglia, and astroglia were each detected via immunofluorescence staining.
      Neuronal apoptosis (marker caspase-3), activated microglia (marker OX42),
      astroglia (marker glial fibrillary acidic protein), and tumor necrosis factor
      alpha expression in microglia and astroglia in the cortex were evaluated by
      immunofluorescence staining methods. RESULTS: Compared with sham-operated
      controls, the TBI-induced proprioception inhibition was significantly attenuated
      by TMX therapy on day 3 after TBI. Using immunofluorescence staining, we found
      that the TBI-induced neuronal loss, apoptosis, activated microglia, and astrocyte
      expression and tumor necrosis factor-alpha and ERalpha in the cortex were
      significantly reduced by TMX therapy. CONCLUSIONS: Our results suggest that the
      intraperitoneal injection of TMX (1 mg/kg/per day) for 3 days may affect ERalpha
      expression in neurons and glia, which is accompanied by neuroinflammation and
      neuronal apoptosis, and it might represent one mechanism by which functional
      recovery occurs. We consider TMX administration to be a promising strategy for
      TBI.

PMID- 29353028
TI  - Reply.

PMID- 29353029
TI  - Applying surgical antimicrobial standards in cesarean deliveries.
AB  - Antimicrobial prophylaxis practices are critical to surgical site infection risk
      reduction strategies. Included in these practices is antibiotic redosing
      following prolonged procedures or after large blood losses. Guidelines have been
      published by several professional associations, with most endorsing repeat
      antibiotic administration after an estimated blood loss of 1500 mL or following 2
      half-lives of the select agent. These conventions have been widely adopted by
      surgeons with the exception of obstetricians at the time of cesarean delivery.
      This Viewpoint explores existing guidelines, reviews the data for these
      recommendations, and questions the tradition of abstinence from redosing in
      cesarean deliveries despite the burden of infection in this cohort.

PMID- 29353030
TI  - Adherence to practice guidelines is associated with reduced referral times for
      patients with ovarian cancer.
AB  - BACKGROUND: Patients with ovarian cancer tend to receive the highest quality of
      care at high-volume cancer centers with gynecological oncologists. However, the
      care that they receive prior to gynecological oncology consult has not been
      examined. We investigated the quantity and quality of care given to patients with
      ovarian cancer before being seen by a gynecological oncologist. OBJECTIVE: We
      evaluated the variability, quantity, and quality of diagnostic testing and
      physician-referral patterns prior to consultation with a gynecological
      oncologist, in women with suspicious pelvic masses seen on imaging. STUDY DESIGN:
      A chart review was performed on patients treated for ovarian cancer at a single
      institution from 2001 to 2014. We evaluated their workup in 4 categories, drawn
      from National Comprehensive Care Network guidelines: provider visits,
      abdominal/pelvic imaging, chest imaging, and tumor markers. Workup was classified
      as guideline adherent or guideline nonadherent. RESULTS: We identified 335 cases
      that met our criteria. In the provider visit category, 83.9% of patients received
      guideline-adherent workup: 77% in the abdominal/pelvic imaging, 98.2% in the
      chest imaging, and 95.2% in the tumor marker categories. Each patient's workup
      was assessed as a compilation of the 4 categories, yielding 65.7% patients as
      having received an adherent workup and 34.3% of workup as nonadherent to
      guidelines. The timeframe to see a gynecological oncologist for patients with
      guideline-adherent workup was significantly shorter than for those whose workup
      was nonadherant (20 vs 86 days, P < .001). A suspicious pelvic mass was
      identified by obstetrics-gynecology in only 23.9% of patients; 42.7% of patients
      did not have tumor marker testing before a gynecological oncologist consult. When
      an obstetrics-gynecology specialist discovered the suspicious pelvic mass, the
      remaining workup was more likely to be guideline adherent prior to gynecological
      oncologist referral than when initial imaging was not ordered by an obstetrics
      gynecology specialist (P = .18). Survival was not significantly different (P =
      .103). CONCLUSION: With a guideline-adherent workup, including tumor marker
      testing, gynecological oncologist referral times can be shortened, minimizing
      cost inefficiencies and delays that can compromise the effectiveness of
      downstream care for patients with ovarian cancer. Guidelines should be
      disseminated beyond the obstetrics-gynecology field.

PMID- 29353031
TI  - Uterine preservation vs hysterectomy in pelvic organ prolapse surgery: a
      systematic review with meta-analysis and clinical practice guidelines.
AB  - OBJECTIVE: We aimed to systematically review the literature on apical pelvic
      organ prolapse surgery with uterine preservation compared with prolapse surgeries
      including hysterectomy and provide evidence-based guidelines. DATA SOURCES: The
      sources for our data were MEDLINE, Cochrane, and clinicaltrials.gov databases
      from inception to January 2017. STUDY ELIGIBILITY CRITERIA: We accepted
      randomized and nonrandomized studies of uterine-preserving prolapse surgeries
      compared with those involving hysterectomy. STUDY APPRAISAL AND SYNTHESIS
      METHODS: Studies were extracted for participant information, intervention,
      comparator, efficacy outcomes, and adverse events, and they were individually and
      collectively assessed for methodological quality. If 3 or more studies compared
      the same surgeries and reported the same outcome, a meta-analysis was performed.
      RESULTS: We screened 4467 abstracts and identified 94 eligible studies, 53
      comparing uterine preservation to hysterectomy in prolapse surgery. Evidence was
      of moderate quality overall. Compared with hysterectomy plus mesh sacrocolpopexy,
      uterine preservation with sacrohysteropexy reduces mesh exposure, operative time,
      blood loss, and surgical cost without differences in prolapse recurrence.
      Compared with vaginal hysterectomy with uterosacral suspension, uterine
      preservation in the form of laparoscopic sacrohysteropexy improves the C point
      and vaginal length on the pelvic organ prolapse quantification exam, estimated
      blood loss, postoperative pain and functioning, and hospital stay, but open
      abdominal sacrohysteropexy worsens bothersome urinary symptoms, operative time,
      and quality of life. Transvaginal mesh hysteropexy (vs with hysterectomy)
      decreases mesh exposure, reoperation for mesh exposure, postoperative bleeding,
      and estimated blood loss and improves posterior pelvic organ prolapse
      quantification measurement. Transvaginal uterosacral or sacrospinous hysteropexy
      or the Manchester procedure compared with vaginal hysterectomy with native tissue
      suspension both showed improved operative time and estimated blood loss and no
      worsening of prolapse outcomes with uterine preservation. However, there is a
      significant lack of data on prolapse outcomes >3 years after surgery, the role of
      uterine preservation in obliterative procedures, and longer-term risk of uterine
      pathology after uterine preservation. CONCLUSION: Uterine-preserving prolapse
      surgeries improve operating time, blood loss, and risk of mesh exposure compared
      with similar surgical routes with concomitant hysterectomy and do not
      significantly change short-term prolapse outcomes. Surgeons may offer uterine
      preservation as an option to appropriate women who desire this choice during
      apical prolapse repair.

PMID- 29353032
TI  - Clinical assessment and brain findings in a cohort of mothers, fetuses and
      infants infected with ZIKA virus.
AB  - BACKGROUND: Congenital Zika virus (ZIKV) infection can be detected in both the
      presence and absence of microcephaly and manifests as a number of signs and
      symptoms that are detected clinically and by neuroimaging. However, to date,
      qualitative and quantitative measures for the purpose of diagnosis and prognosis
      are limited. OBJECTIVES: Main objectives of this study conducted on fetuses and
      infants with confirmed congenital Zika virus infection and detected brain
      abnormalities were (1) to assess the prevalence of microcephaly and the frequency
      of the anomalies that include a detailed description based on ultrasound and
      magnetic resonance imaging in fetuses and ultrasound, magnetic resonance imaging,
      and computed tomography imaging postnatally, (2) to provide quantitative measures
      of fetal and infant brain findings by magnetic resonance imaging with the use of
      volumetric analyses and diffusion-weighted imaging, and (3) to obtain additional
      information from placental and fetal histopathologic assessments and postnatal
      clinical evaluations. STUDY DESIGN: This is a longitudinal cohort study of Zika
      virus-infected pregnancies from a single institution in Colombia. Clinical and
      imaging findings of patients with laboratory-confirmed Zika virus infection and
      fetal brain anomalies were the focus of this study. Patients underwent monthly
      fetal ultrasound scans, neurosonography, and a fetal magnetic resonance imaging.
      Postnatally, infant brain assessment was offered by the use of ultrasound
      imaging, magnetic resonance imaging, and/or computed tomography. Fetal head
      circumference measurements were compared with different reference ranges with <2
      or <3 standard deviations below the mean for the diagnosis of microcephaly. Fetal
      and infant magnetic resonance imaging images were processed to obtain a
      quantitative brain volumetric assessment. Diffusion weighted imaging sequences
      were processed to assess brain microstructure. Anthropometric, neurologic,
      auditory, and visual assessments were performed postnatally. Histopathologic
      assessment was included if patients opted for pregnancy termination. RESULTS: All
      women (n=214) had been referred for Zika virus symptoms during pregnancy that
      affected themselves or their partners or if fetal anomalies that are compatible
      with congenital Zika virus syndrome were detected. A total of 12 pregnant
      patients with laboratory confirmation of Zika virus infection were diagnosed with
      fetal brain malformations. Most common findings that were assessed by prenatal
      and postnatal imaging were brain volume loss (92%), calcifications (92%),
      callosal anomalies (100%), cortical malformations (89%), and ventriculomegaly
      (92%). Results from fetal brain volumetric assessment by magnetic resonance
      imaging showed that 1 of the most common findings associated with microcephaly
      was reduced supratentorial brain parenchyma and increased subarachnoid
      cerebrospinal fluid. Diffusion weighted imaging analyses of apparent diffusion
      coefficient values showed microstructural changes. Microcephaly was present in
      33.3-58.3% of the cases at referral and was present at delivery in 55.6-77.8% of
      cases. At birth, most of the affected neonates (55.6-77.8%) had head
      circumference measurements >3 standard deviations below the mean. Postnatal
      imaging studies confirmed brain malformations that were detected prenatally.
      Auditory screening results were normal in 2 cases that were assessed. Visual
      screening showed different anomalies in 2 of the 3 cases that were examined.
      Pathologic results that were obtained from 2 of the 3 cases who opted for
      termination showed similar signs of abnormalities in the central nervous system
      and placental analyses, including brain microcalcifications. CONCLUSION:
      Congenital microcephaly is not an optimal screening method for congenital Zika
      virus syndrome, because it may not accompany other evident and preceding brain
      findings; microcephaly could be an endpoint of the disease that results from
      progressive changes that are related to brain volume loss. Long-term studies are
      needed to understand the clinical and developmental relevance of these findings.

PMID- 29353033
TI  - Acetylsalicylic acid in pregnant women with chronic hypertension.

PMID- 29353034
TI  - Impact of targeted scanning protocols on perinatal outcomes in pregnancies at
      risk of placenta accreta spectrum or vasa previa.
AB  - BACKGROUND: Placenta accreta spectrum and vasa previa (VP) are congenital
      disorders of placentation associated with high morbidity and mortality for both
      mothers and newborns when undiagnosed before delivery. Prenatal diagnosis of
      these conditions is essential to allow multidisciplinary management and thus
      improve perinatal outcomes. OBJECTIVE: The objective of the study was to compare
      perinatal outcome in women with placenta accreta spectrum or vasa previa before
      and after implementation of targeted scanning protocols. STUDY DESIGN: This
      retrospective study included 2 nonconcurrent cohorts for each condition before
      and after implementation of the corresponding protocols (2004-1012 vs 2013-2016
      for placenta accreta spectrum and 1988-2007 vs 2008-2016 for vasa previa).
      Clinical reports of women diagnosed with placenta accreta spectrum and vasa
      previa during the study periods were reviewed and outcomes were compared.
      RESULTS: In total, there were 97 cases of placenta accreta spectrum and 51 cases
      with vasa previa, all confirmed at delivery. In both cohorts, the prenatal
      detection rate increased after implementation of the scanning protocols (28 of 65
      cases [43.1%] vs 31 of 32 cases [96.9%], P < .001, for placenta accreta spectrum
      and 9 of 18 cases [50%] vs 29 of 33 cases [87.9%], 87.9%, P < .01 for vasa
      previa). The perinatal outcome improved also significantly in both cohorts after
      implementation of the protocols. In the placenta accreta spectrum cohort, the
      estimated blood loss and the postoperative hospitalization stay decreased between
      periods (1520 +/- 845 vs 1168 +/- 707 mL, P < .01, and 10.9 +/- 14.1 vs 5.7 +/-
      2.2 days, P < .05, respectively). In the vasa previa cohort, the number of 5
      minute Apgar score <=5 and umbilical cord pH <7 decreased between periods (5 of
      18 cases [27.8%] vs 1 of 33 cases [3%]; P < .05, and 4 of 18 cases [22.2%] vs 1
      of 33 cases [3%], P < .05, respectively). CONCLUSION: The implementation of
      standardized prenatal targeted scanning protocols for pregnant women with risk
      factors for placenta accreta spectrum and vasa previa was associated with
      improved maternal and neonatal outcomes. The continuous increases in the rates of
      caesarean deliveries and use of assisted reproductive technology highlights the
      need to develop training programs and introduce targeted scanning protocols at
      the national and international levels.

PMID- 29353035
TI  - Fellow perceptions of residency training in obstetrics and gynecology.

PMID- 29353036
TI  - NMR-based serum metabolomics study reveals a innovative diagnostic model for
      missed abortion.
AB  - A missed abortion (MA) is an in-utero death of the embryo or fetus before the
      20th week of gestation with retained products of conception. In order to discover
      novel biomarkers for MA, a 1H NMR spectroscopy-based metabolomics approach was
      applied to detect human MA serum metabolic profiles. Serum samples were obtained
      from patients with MA (n = 15) and healthy controls (n = 9) for study. The
      NOESYPR1D spectrum combined with multi-variate pattern recognition analysis was
      used to cluster the groups and establish a disease-specific metabolites
      phenotype. Principal component analysis (PCA) and orthogonal partial least
      squares discriminant analysis (OPLS-DA) models were capable of distinguishing MA
      patients from healthy subjects. The results revealed that 24 metabolites altered
      in MA patients compared with the control population. Metabolomic pathway analysis
      demonstrated that alanine, aspartate and glutamate metabolism, citrate cycle (TCA
      cycle), taurine and hypotaurine metabolism were significantly altered in MA. The
      results indicated that serum NMR-based metabolomic profiling method is sensitive
      and specific enough to distinguish MA and from healthy controls, this method
      could be developed as a clinically useful diagnostic tool for MA. The finding
      from the MA serum metabolic profiling shed a new light on further understanding
      of MA disease mechanisms.

PMID- 29353037
TI  - Curcumin protects cortical neurons against oxygen and glucose
      deprivation/reoxygenation injury through flotillin-1 and extracellular signal
      regulated kinase1/2 pathway.
AB  - In this study, we provided evidence that curcumin could be a promising
      therapeutic agent for ischemic stroke by activating neuroprotective signaling
      pathways. Post oxygen and glucose deprivation/reoxygenation (OGD/R), primary
      mouse cortical neurons treated with curcumin exhibited a significant decrease in
      cell death, LDH release and enzyme caspase-3 activity under OGD/R circumstances,
      which were abolished by flotillin-1 downregulation or extracellular signal
      regulated kinase (ERK) inhibitor. Moreover, flotillin-1 knockdown led to
      suppression of curcumin-mediated ERK phosphorylation under OGD/R condition. Based
      on these findings, we concluded that curcumin could confer neuroprotection
      against OGD/R injury through a novel flotillin-1 and ERK1/2 pathway.

PMID- 29353039
TI  - WITHDRAWN: Cetylpyridinium chloride as a novel inhibitor of hepatitis B viral
      capsid assembly.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29353038
TI  - Cereblon (CRBN) deletion reverses streptozotocin induced diabetic osteoporosis in
      mice.
AB  - Diabetes mellitus is a major cause to induce osteoporosis. Though the
      pathogenesis of osteoporosis progression has been well investigated, its still
      not fully understood. Recently, cereblon (CRBN) was considered as a negative
      modulator of adenosine monophosphate-activated protein kinase (AMPK) in vitro and
      in vivo. Here, we presented results indicating that CRBN could effectively
      regulate osteoporosis development. In STZ-induced wild type (WT) mice with
      diabetes, the osteoclasts were highly increased along with the deterioration of
      bone structure. However, CRBN knockout (KO) reduced blood glucose the levels and
      attenuated insulin resistance. What's more, CRBN ablation suppressed osteoclast
      differentiation and rescued diabetic bone loss in vivo, accompanied with
      decreased receptor activator of NF-kB ligand (RANKL), RANKL/osteoprotegerin
      (OPG), and tartrate-resistant acid phosphatase (TRAP) levels, as well as improved
      AMP-activated kinase (AMPK) alpha/acetyl-CoA carboxylase (ACC)alphaactivation. In
      vitro, suppressing CRBN expression could reduce RANKL-induced osteoclastogenesis,
      supported by the reduction of TRAP-positive cells. CRBN knockdown (KD) obviously
      reduced RANKL-induced activity of IkappaBalpha/nuclear factor-kappaB (NF-kappaB)
      pathway. In addition, osteoclast-specific genes expression levels stimulated by
      RANKL were also decreased by CRBN silence. More importantly, CRBN blockage
      increased phosphorylated AMPK-alpha and ACC-alpha expressions in RANKL-incubated
      cells. However, these processes could be abolished by suppressing AMPK-alpha with
      its inhibitor, Compound C. Collectively, our data suggested that CRBN is a
      potential treatment option against diabetes-induced osteolytic bone disease.

PMID- 29353040
TI  - Eupatilin, an activator of PPARalpha, inhibits the development of oxazolone
      induced atopic dermatitis symptoms in Balb/c mice.
AB  - Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the main lipophilic
      flavonoid obtained from the Artemisia species. Eupatilin has been reported to
      have anti-apoptotic, anti-oxidative and anti-inflammatory activities. Previously,
      we found that eupatilin increases transcriptional activity and expression of
      peroxisome proliferator-activated receptor alpha (PPARalpha) in a keratinocyte
      cell line and acts as an agonist of PPARalpha. PPARalpha agonists ameliorate
      atopic dermatitis (AD) and restore the skin barrier function. In this study, we
      confirmed that the effects of eupatilin improved AD-like symptoms in an oxazolone
      induced AD-like mouse model. Furthermore, we found that eupatilin suppressed the
      levels of serum immunoglobulin E (IgE), interleukin-4 (IL-4), and AD involved
      cytokines, such as tumor necrosis factor alpha (TNFalpha), interferon-gamma (IFN
      gamma), IL-1beta, and thymic stromal lymphopoietin (TSLP), IL-33, IL-25 and
      increased the levels of filaggrin and loricrin in the oxazolone-induced AD-like
      mouse model. Taken together, our data suggest that eupatilin is a potential
      candidate for the treatment of AD.

PMID- 29353041
TI  - FADS2 inhibition in essential fatty acid deficiency induces hepatic lipid
      accumulation via impairment of very low-density lipoprotein (VLDL) secretion.
AB  - Fatty acid desaturase 2 (FADS2) is responsible for the first desaturation
      reaction in the synthesis of highly unsaturated fatty acids (HUFAs), such as
      arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3), and is involved
      in Mead acid (20:3n-9) production during essential fatty acid deficiency (EFAD).
      In this study, an obvious hepatic lipid accumulation was observed in EFAD mice
      treated with a FADS2 inhibitor. FADS2 inhibition in the EFAD state reduced
      secretion of very low-density lipoprotein (VLDL) and markedly diminished Mead
      acid in phosphatidylcholine (PC) in the liver and plasma. As the results, the
      amount of C20 HUFAs in hepatic and plasma PC dramatically reduced in the EFAD
      mice treated with a FADS2 inhibitor, whereas the decrease of C20 HUFA levels of
      PC in EFAD mice was not observed because of the increased Mead acid in PC. These
      results supposed that Mead acid in PC is important as a component of VLDL. It is
      possible that Mead acid plays the role of a substitute of HUFAs in VLDL secretion
      during EFAD.

PMID- 29353042
TI  - Ginkgolic acid induces interplay between apoptosis and autophagy regulated by ROS
      generation in colon cancer.
AB  - Presently, developing effective anti-colon cancer drugs still remains to be
      important. Ginkgolic acids (GA), as a botanical drug extracted from the seed coat
      of Ginkgo biloba L., possess various bioactive properties. Our findings, for the
      first time, indicated that GA suppressed colon cancer cell proliferation,
      migration and invasion. GA led to cell death through G0/G1 phase arrest. In
      addition, apoptosis was significantly induced by GA treatment. The intrinsic
      apoptosis pathway was included, proved by the release of cytochrome c (Cyto-c)
      from the mitochondria into the cytosol. GA-induced autophagy was supported by the
      dose-dependent increase of LC3BII, autophagy-related gene-5 (ATG-5) and Beclin-1.
      Notably, silencing ATG-5 further reduced the cell viability and enhanced
      apoptosis in GA-treated colon cancer cells, indicating that GA-induced apoptosis
      rather than autophagy contributes to colon cancer cell death. And mammalian
      target of rapamycin complex 1 (mTORC1) was dose-dependently reduced by GA,
      evidenced by the reduction of p-mTOR, p-p70 ribosomal S6 kinase (p70s6k) and p
      pras40. Moreover, GA markedly resulted in reactive oxygen species (ROS)
      generation, along with increased H2O2 and O2-. However, blocking ROS generation
      using its scavenger, NAC, significantly recovered GA-induced cells death,
      supported by the increase of cell viability, and the decrease of apoptosis. The
      expressions of autophagy- and cell cycle arrest-related molecules, as well as
      mTORC1 were also reversed by N-acetyl-l-cysteine (NAC) in GA-treated cells. In
      vivo, GA reduced tumor growth without toxicity to animals. In conclusion, our
      study illustrated that GA caused G0/G1 phase arrest and triggered intrinsic
      apoptosis and autophagy modulated by ROS generation in human colon cancer,
      elucidating that GA might be considered as a potential agent for colon cancer
      therapy.

PMID- 29353043
TI  - Progression of vasogenic edema induced by activated microglia under permanent
      middle cerebral artery occlusion.
AB  - Brain edema is a severe complication that accompanies ischemic stroke. Increasing
      evidence shows that inflammatory cytokines impair tight junctions of the blood
      brain barrier, suggesting the involvement of microglia in brain edema. In this
      study, we examined the role of microglia in the progression of ischemic brain
      edema using mice with permanent middle cerebral artery occlusion. The intensity
      of T2-weighted imaging (T2WI) in the cerebral cortex and the striatum was
      elevated 3 h after occlusion and spread to peripheral regions of the ischemic
      hemisphere. Merged images of 2,3,5-triphenyl tetrazolium chloride staining and
      T2WI revealed the exact vasogenic edema region, which spread from the ischemic
      core to outside the ischemic region. Microglia were strongly activated in the
      ischemic region 3 h after occlusion and, notably, activated microglia were
      observed in the non-ischemic region 24 h after occlusion. Pretreatment with
      minocycline, an inhibitor of microglial activation clearly suppressed not only
      vasogenic edema but also infarct formation. We demonstrated in this study that
      vasogenic edema spreads from the ischemic core to the peripheral region, which
      can be elicited, at least in part, by microglial activation induced by ischemia.

PMID- 29353044
TI  - BMP4 signaling in NPCs upregulates Bcl-xL to promote their survival in the
      presence of FGF-2.
AB  - We previously reported that BMP4 does not promote proliferation or
      differentiation of CD44-positive astrocyte precursor cells (APCs) but greatly
      promotes their survival in the presence of fibroblast growth factor-2 (FGF-2). In
      this study, we examined if BMP4 acts as a survival factor also for neural
      stem/progenitor cells (NPCs) isolated from ganglionic eminence of neonatal mouse
      brain. We found BMP4 promotes survival but not proliferation or differentiation
      of these cells, just as in the case for CD44-positive APCs. Microarray analysis
      revealed some candidate molecules in the signaling pathway downstream of BMP4.
      Among them, we focused on Id1 (inhibitor of DNA-binding 1) and Bcl-xL in this
      study. Expression of both genes was promoted in the presence of BMP4, and this
      promotion was reduced by dorsomorphin, an inhibitor of BMP4 signaling.
      Furthermore, cytochrome c release from mitochondria was significantly reduced in
      the presence of BMP4, suggesting up-regulation of Bcl-xL activity by BMP4. Id1
      siRNA reduced the expression of Bcl-xL, and negated survival promoting effect of
      BMP4. These data suggest that BMP4 promotes survival of NPCs by enhancing the
      anti-apoptotic function of Bcl-xL via BMP4-Smad1/5/8-Id1 signaling.

PMID- 29353045
TI  - Functionally compromised synovium-derived mesenchymal stem cells in Charcot
      neuroarthropathy.
AB  - Charcot neuroarthropathy (CNA) often presents as a diabetic foot complication.
      The role of synovial mesenchymal stem cells (syn-MSCs) in the pathogenesis of CNA
      is unclear. Synovial samples were collected, for isolation of syn-MSCs, from
      diabetic patients with CNA (n=7) and non-diabetic patients with intra-articular
      fracture or normal joints (non-CNA; n=7) during foot surgery. The syn-MSCs in the
      CNA and non-CNA groups were characterized comparatively. The average number of
      colonies formed in the CNA group was 6+/-3.5 per half plate (10mm in diameter),
      while it was 43+/-21.6 in the non-CNA group (p<0.05). The average size (pixels)
      of the colonies in the CNA group was smaller than that in the non-CNA group. When
      the colonies were stratified into high-, medium- and low-density subgroups,
      colonies in the high-density subgroup of the CNA group were reduced in density.
      Expression of PPAR-gamma, RUNX2, Sox9 and type II collagen by syn-MSCs in the CNA
      group was decreased during adipogenic, osteogenic and chondrogenic
      differentiation as compared with the non-CNA group. In conclusion, syn-MSCs in
      CNA joints were reduced in number, with declined differentiation potentials. The
      high-density subpopulation of the syn-MSCs was particularly affected by the
      pathology of CNA.

PMID- 29353046
TI  - Gas Within the Bladder.

PMID- 29353047
TI  - Clinical Profile of Nonresponders to Surgical Myectomy with Obstructive
      Hypertrophic Cardiomyopathy.
AB  - BACKGROUND: Surgical myectomy reverses heart failure symptoms in the vast
      majority of obstructive hypertrophic cardiomyopathy patients. However, a small
      subgroup fails to experience sustained postoperative improvement despite relief
      of obstruction. Clinical profile of such patients has not been well defined.
      METHODS: Consecutive obstructive hypertrophic cardiomyopathy patients undergoing
      myectomy at Tufts Medical Center for drug-refractory New York Heart Association
      III/IV heart failure symptoms, 2004 to 2017, were followed postoperatively for
      2.5 +/- 2.8 years and assessed for outcome. RESULTS: Of the 503 patients, there
      were 4 postoperative deaths (0.8%); 480 patients (96%) had sustained improvement
      to New York Heart Association classes I or II (responders), but 19 (3.8%)
      developed advanced symptoms (classes III or IV) in the absence of obstruction
      (nonresponders). Compared with responders, nonresponders were younger (40 +/- 13
      vs 53 +/- 14 years; P < .001) and had greater septal thickness (25 +/- 9 vs 20 +/
      4 mm; P < .001). Massive hypertrophy (>=30 mm) was 5-fold more common in
      nonresponders (P < .01). Seven nonresponders developed systolic dysfunction
      (ejection fraction 20%-47%), 2 days to 6.1 years postoperatively. Four
      nonresponders underwent heart transplant 3.4 to 9.2 years after myectomy, and 2
      others have been listed. CONCLUSIONS: Surgical myectomy is highly effective at
      reversing heart failure symptoms in the vast majority of patients with
      obstructive hypertrophic cardiomyopathy. However, a small minority experience
      persistent functional limitation despite surgical relief of outflow obstruction.
      Predictors of adverse postoperative course were substantial/massive septal
      thickness and youthful age. Patients who failed to respond symptomatically to
      myectomy were considered for advanced heart failure treatment, including heart
      transplantation.

PMID- 29353048
TI  - Cardiac Events after Noncardiac Surgery in Patients Undergoing Preoperative
      Dobutamine Stress Echocardiography: Findings From the Mayo Poce-DSE
      Investigators.
AB  - BACKGROUND: Current guidelines support the use of dobutamine stress
      echocardiography (DSE) prior to noncardiac surgery in higher-risk patients who
      are unable to perform at least 4 metabolic equivalents of physical activity. We
      evaluated postoperative outcomes of patients in different operative risk
      categories after preoperative DSE. METHODS: We collected data from the medical
      record on 4494 patients from January 1, 2006 to December 31, 2011 who had DSE up
      to 90 days prior to a noncardiac surgery. Patients were divided into low,
      intermediate, and high preoperative surgery-specific risk. Baseline demographic
      data and risk factors were abstracted from the medical record, as were
      postoperative cardiac events including myocardial infarction, cardiac arrest, and
      mortality within 30 days after surgery. RESULTS: There were 103 cardiac outcomes
      (2.3%), which included myocardial infarction (n = 57, 1.3%), resuscitated cardiac
      arrest (n = 26, 0.6%), and all-cause mortality (n = 40, 0.9%). Cardiac event
      rates were 0.0% (95% confidence interval [CI], 0.0%-3.9%) in the low-surgical
      risk group, 2.1% (95% CI, 1.6%-2.5%) in the intermediate-surgical-risk group, and
      3.4% (95% CI, 2.0%-4.4%) in the high-risk group. Thirty-day postoperative
      mortality rates were 0%, 0.9%, and 0.8% for the low-risk, intermediate-risk, and
      high-risk surgical groups, respectively, and were not statistically different.
      CONCLUSIONS: These findings demonstrate low cardiac event rates in patients who
      underwent a DSE prior to noncardiac surgery. The previously accepted construct of
      low-, intermediate-, and high-risk surgeries based on postoperative events of
      <1%, 1%-5%, and >5% overestimates the actual risk in contemporary settings.

PMID- 29353049
TI  - Candid to the Bitter End: Indiscriminate Disclosures.

PMID- 29353050
TI  - Helicobacter pylori Infection: An Update for the Internist in the Age of
      Increasing Global Antibiotic Resistance.
AB  - Helicobacter pylori infects approximately half the world's population and is
      especially prevalent in the developing world. H. pylori is an important cause of
      global ill health due to its known etiological role in peptic ulcer disease,
      dyspepsia, gastric cancer, lymphoma, and more recently, recognized in iron
      deficiency anemia and idiopathic thrombocytopenic purpura. Increased antibiotic
      usage worldwide has led to antibiotic resistance among many bacteria, including
      H. pylori, resulting in falling success rates of first-line anti-H. pylori
      therapies. Eradication failures are principally due to resistance to
      clarithromycin, levofloxacin, and metronidazole. Several new treatment options or
      modifications of established regimens are now recommended by updated practice
      guidelines for primary or secondary therapy. Because these updated
      recommendations were published in the gastroenterological literature, internists
      and primary care physicians, who commonly manage H. pylori, may be unaware of
      these advances. In this review, we outline the changing epidemiology of H.
      pylori, advise on diagnostic test selection for patients not undergoing
      endoscopy, and highlight current management options in this era of growing
      antibacterial resistance.

PMID- 29353051
TI  - Infrequent isolation of extensively drug-resistant (XDR) Klebsiella pneumoniae
      resistant to colistin in Spain.

PMID- 29353052
TI  - Evidence for altered insulin receptor signaling in Alzheimer's disease.
AB  - Epidemiological data have shown that metabolic disease can increase the
      propensity for developing cognitive decline and dementia, particularly
      Alzheimer's disease (AD). While this interaction is not completely understood,
      clinical studies suggest that both hyper- and hypoinsulinemia are associated with
      an increased risk for developing AD. Indeed, insulin signaling is altered in post
      mortem brain tissue from AD patients and treatments known to enhance insulin
      signaling can improve cognitive function. Further, clinical evidence has shown
      that AD patients and mouse models of AD often display alterations in peripheral
      metabolism. Since insulin is primarily derived from the periphery, it is likely
      that changes in peripheral insulin levels lead to alterations in central nervous
      system (CNS) insulin signaling and could contribute to cognitive decline and
      pathogenesis. Developing a better understanding of the relationship between
      alterations in peripheral metabolism and cognitive function might provide a
      foundation for the development of better treatment options for patients with AD.
      In this article we will begin to piece together the present data defining this
      relationship by briefly discussing insulin signaling in the periphery and CNS,
      its role in cognitive function, insulin's relationship to AD, peripheral
      metabolic alterations in mouse models of AD and how information from these models
      helps understand the mechanisms through which these changes potentially lead to
      impairments in insulin signaling in the CNS, and potential ways to target insulin
      signaling that could improve cognitive function in AD. This article is part of
      the Special Issue entitled 'Metabolic Impairment as Risk Factors for
      Neurodegenerative Disorders.'

PMID- 29353054
TI  - The role of the vasopressin V1A receptor in oxytocin modulation of
      methamphetamine primed reinstatement.
AB  - The neuropeptide oxytocin has shown promise as an effective therapy in pre
      clinical models of methamphetamine (METH) addiction. The nucleus accumbens core
      (NAcc) has been identified as an important site for oxytocin to inhibit METH
      behaviours, although previous findings suggest that the effects of oxytocin in
      the NAcc are mediated by receptors other than the oxytocin receptor (OTR).
      Oxytocin has high affinity for the vasopressin V1A receptor (V1AR) which has been
      implicated in numerous oxytocin-dependent social behaviours. The aim of this
      study was to investigate the involvement of the V1AR in mediating the effect of
      oxytocin treatment to reduce METH-primed reinstatement of METH-seeking behaviour.
      Male rats were trained to self-administer intravenous infusions of METH by lever
      press during daily 2-h fixed ratio 1 scheduled sessions for 20 days. Following
      extinction of lever pressing, rats were tested for the effects of oxytocin alone,
      oxytocin co-administered with a selective V1AR antagonist, or oxytocin co
      administered with a selective OTR antagonist, on METH-primed reinstatement, when
      administered systemically, or when microinjected into the NAcc. Systemic
      administration of oxytocin prevented METH-primed reinstatement, an effect which
      was significantly reduced by systemic pre-treatment with a V1AR but not OTR
      antagonist. Local administration of oxytocin into the NAcc reduced METH-primed
      reinstatement, but not when the V1AR was blocked. Our results demonstrate a
      substantial role for the V1AR in mediating the inhibitory effects of oxytocin on
      METH-primed reinstatement, and indicate the need for investigations into the
      differential involvement of V1ARs and OTRs in oxytocin-induced reduction of METH
      related behaviours.

PMID- 29353053
TI  - Conditional inactivation of Npy1r gene in mice induces behavioural inflexibility
      and orbitofrontal cortex hyperactivity that are reversed by escitalopram.
AB  - Cognitive flexibility is the ability to rapidly adapt established patterns of
      behaviour in the face of changing circumstance and depends critically on the
      orbitofrontal cortex (OFC). Impaired flexibility also results from altered
      serotonin transmission in the OFC. The Y1 (Y1R) and Y5 (Y5R) receptors for
      neuropeptide Y (NPY) colocalize in several brain regions and have overlapping
      functions in regulating cognition and emotional behaviour. The targeted
      disruption of gene encoding Y1R (Npy1r gene) in Y5R containing neurons (Npy1rY5R
      /- mice) increases anxiety-like behaviour and spatial reference memory. Here we
      used the same conditional system to analyse whether the coordinated expression of
      the Y1R and Y5R might be required for behavioural flexibility in reversal
      learning tasks, OFC serotoninergic tone and OFC neural activity, as detected by
      immunohistochemical quantification of the immediate-early gene, c-Fos. In
      addition, we investigated whether the acute treatment of Npy1rY5R-/- mice with
      the selective serotonin reuptake inhibitor escitalopram affected behavioural
      flexibility and OFC c-Fos expression. Npy1rY5R-/- male mice exhibit an impairment
      in performing the reversal task of the Morris water maze and the water T-maze but
      normal spatial learning, working memory and sociability, compared to their
      control siblings. Furthermore, Npy1rY5R-/- male mice display decreased 5
      hydroxytriptamine (5-HT) positive fibres and increased baseline neural activity
      in OFC. Importantly, escitalopram normalizes OFC neural activity and restores
      behavioural flexibility of Npy1rY5R-/- male mice. These findings suggest that the
      inactivation of Y1R in Y5R containing neurons increases pyramidal neuron activity
      and dysregulates serotoninergic tone in OFC, whereby contributing to reversal
      learning impairment.

PMID- 29353055
TI  - Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling in the
      prefrontal cortex modulates cued fear learning, but not spatial working memory,
      in female rats.
AB  - A genetic polymorphism within the gene encoding the pituitary adenylate cyclase-
      activating polypeptide (PACAP) receptor type I (PAC1R) has recently been
      associated with hyper-reactivity to threat-related cues in women, but not men,
      with post-traumatic stress disorder (PTSD). PACAP is a highly conserved peptide,
      whose role in mediating adaptive physiological stress responses is well
      established. Far less is understood about the contribution of PACAP signaling in
      emotional learning and memory, particularly the encoding of fear to discrete
      cues. Moreover, a neurobiological substrate that may account for the observed
      link between PAC1R and PTSD in women, but not men, has yet to be identified. Sex
      differences in PACAP signaling during emotional learning could provide novel
      targets for the treatment of PTSD. Here we investigated the contribution of PAC1R
      signaling within the prefrontal cortex to the acquisition of cued fear in female
      and male rats. We used a variant of fear conditioning called trace fear
      conditioning, which requires sustained attention to fear cues and depends on
      working-memory like neuronal activity within the prefrontal cortex. We found that
      cued fear learning, but not spatial working memory, was impaired by
      administration of a PAC1R antagonist directly into the prelimbic area of the
      prefrontal cortex. This effect was specific to females. We also found that levels
      of mRNA for the PAC1R receptor in the prelimbic cortex were greater in females
      compared with males, and were highest during and immediately following the
      proestrus stage of the estrous cycle. Together, these results demonstrate a sex
      specific role of PAC1R signaling in learning about threat-related cues.

PMID- 29353057
TI  - Mechanisms of Enhanced Osteoclastogenesis in Alkaptonuria.
AB  - Alkaptonuria (AKU) is a rare disorder characterized by the deficiency of the
      enzyme homogentisate 1,2-dioxygenase and consequent homogentisate accumulation,
      which leads to progressive and severe osteoarthopathy starting from the second
      decade of life. Thus, in AKU patients, bone involvement represents an important
      clinical issue, which we investigated. Serum levels of receptor activator of NF
      kappaB ligand (RANKL), osteoprotegerin, sclerostin, Dickkopf-1, and bone
      remodeling markers were measured in nine AKU patients (two children and seven
      adults) and 22 controls, together with lumbar spine bone mineral density (LS-BMD)
      and femoral-BMD. In the two AKU children, the average of LS-BMD and femoral-BMD Z
      scores were within the normal range, but reduced with respect to the controls.
      Otherwise, in the adult AKU patients, LS-BMD T-score was inside the normal range,
      but femoral-BMD T-score reached osteopenic levels. Consistently, in AKU adults,
      higher RANKL and C-terminal telopeptide of collagen type 1 and lower
      osteoprotegerin levels were observed than in controls. Otherwise, spontaneous
      osteoclastogenesis was already evident in peripheral blood mononuclear cell
      cultures from AKU children, together with a high percentage of circulating
      osteoclast precursors. Osteoclastogenesis was sustained by the high levels of
      tumor necrosis factor-alpha, RANK, RANKL, and LIGHT. In conclusion, the altered
      osteoclastogenesis was observed already in AKU children, despite the absence of
      evident injury. Thus, a preventive approach in young patients, targeting
      osteoclast activity, may prevent the macroscopic bone disease that appears in
      adult AKU.

PMID- 29353059
TI  - ASK Family Kinases Are Required for Optimal NLRP3 Inflammasome Priming.
AB  - Activation of the multimeric inflammasome complex leads to inflammatory responses
      to biotic and abiotic triggers. The inflammasome sensor, Nod-like receptor family
      pyrin domain containing 3 (NLRP3), is activated by a range of stimuli and is
      tightly regulated to restrict excessive inflammation. Because NLRP3 responds
      broadly to cellular insults and regulates cell death similar to the stress
      activated apoptosis signal-regulating kinases 1 and 2 (ASK1/2), we hypothesized
      that ASK1/2 may regulate NLRP3 activity. Although essential for mediating NLRP3
      inflammasome activation, ASK1/2 were not required for NLRC4 or absent in melanoma
      2 inflammasome activation. ASK1/2 was required for NLRP3 up-regulation after
      lipopolysaccharide treatment in primary bone marrow-derived macrophages and lung
      fibroblasts as well as during infection with Burkholderia thailandensis and
      influenza virus. Consistent with reduced NLRP3 expression in response to B.
      thailandensis, caspase-1 cleavage and cell death were reduced in infected bone
      marrow-derived macrophages, and mice lacking ASK1/2 were resistant to
      Burkholderia intranasal infection. Single knockouts of either ASK1 or ASK2 showed
      a partial role for both ASK1 and ASK2 in NLRP3 up-regulation in response to
      lipopolysaccharide or B. thailandensis, but ASK2 was required primarily to
      mediate lethal pathology during intranasal infection in vivo. Our findings
      identify the ASK1/2 complex as a regulator of NLRP3 activation and highlight a
      larger role for ASK2 in lung infection during B. thailandensis infection.

PMID- 29353056
TI  - Interspecific studies of circadian genes period and timeless in Drosophila.
AB  - The level of rescue of clock function in genetically arrhythmic Drosophila
      melanogaster hosts using interspecific clock gene transformation was used to
      study the putative intermolecular coevolution between interacting clock proteins.
      Among them PER and TIM are the two important negative regulators of the circadian
      clock feedback loop. We transformed either the D. pseudoobscura per or tim
      transgenes into the corresponding arrhythmic D. melanogaster mutant (per01 or
      tim01) and observed >50% rhythmicity but the period of activity rhythm was either
      longer (D. pseudoobscura-per) or shorter than 24 h (D. pseudoobscura-tim)
      compared to controls. By introducing both transgenes simultaneously into double
      mutants, we observed that the period of the activity rhythm was rescued by the
      pair of hemizygous transgenes (~24 h). These flies also showed a more optimal
      level of temperature compensation for the period. Under LD 12:12 these flies have
      a D. pseudoobscura like activity profile with the absence of morning anticipation
      as well as a very prominent earlier evening peak of activity rhythm. These
      observation are consistent with the view that TIM and PER form a heterospecific
      coevolved module at least for the circadian period of activity rhythms. However
      the strength of rhythmicity was reduced by having both transgenes present, so
      while evidence for a coevolution between PER and TIM is observed for some
      characters it is not for others.

PMID- 29353058
TI  - Chd7 Is Critical for Early T-Cell Development and Thymus Organogenesis in
      Zebrafish.
AB  - Coloboma, heart defect, atresia choanae, retarded growth and development, genital
      hypoplasia, ear anomalies/deafness (CHARGE) syndrome is a congenital disorder
      affecting multiple organs and mainly caused by mutations in CHD7, a gene encoding
      a chromatin-remodeling protein. Immunodeficiency and reduced T cells have been
      noted in CHARGE syndrome. However, the mechanisms underlying T lymphopenia are
      largely unexplored. Herein, we observed dramatic decrease of T cells in both
      chd7knockdown and knockout zebrafish embryos. Unexpectedly, hematopoietic stem
      and progenitor cells and, particularly, lymphoid progenitor cells were increased
      peripherally in nonthymic areas in chd7-deficient embryos, unlikely to contribute
      to the T-cell decrease. Further analysis demonstrated that both the organogenesis
      and homing function of the thymus were seriously impaired. Chd7 might regulate
      thymus organogenesis through modulating the development of both neural crest cell
      derived mesenchyme and pharyngeal endoderm-derived thymic epithelial cells. The
      expression of foxn1, a central regulator of thymic epithelium, was remarkably
      down-regulated in the pharyngeal region in chd7-deficient embryos. Moreover, the
      T-cell reduction in chd7-deficient embryos was partially rescued by
      overexpressing foxn1, suggesting that restoring thymic epithelium may be a
      potential therapeutic strategy for treating immunodeficiency in CHARGE syndrome.
      Collectively, the results indicated that chd7 was critical for thymic development
      and T-lymphopenia in CHARGE syndrome may be mainly attributed to the defects of
      thymic organogenesis. The current finding may benefit the diagnosis and therapy
      of T lymphopenia and immunodeficiency in CHARGE syndrome.

PMID- 29353060
TI  - Parathyroid Hormone-Related Protein Contributes to Early Healing of Habu Snake
      Venom-Induced Glomerulonephritis in Mice.
AB  - Proliferative glomerulonephritis is characterized by local inflammation and
      mesangial cell deterioration, followed by mesangial proliferation and glomerular
      healing. Parathyroid hormone-related peptide (PTHrP) is a mesangial cytokine-like
      growth factor implicated in mesangial proliferation and survival. No data are
      available about its role in glomerulonephritis. Herein, we analyzed the
      expression and role of PTHrP in glomerular inflammation and healing in an
      experimental model of glomerulonephritis induced by i.v. injection of Habu snake
      venom in mice. The temporal analysis showed marked renal damage in the first days
      after venom injection and the beginning of recovery within 7 days. Glomerular
      expression of PTHrP (transcript and protein) was observed in the early phase
      after venom injection (from day 1 to day 3), along with an inflammatory
      environment. The inactivation of secreted PTHrP with PTHrP-neutralizing antibody
      (PTH2E11; 120 MUg i.p. daily) reduced the markers of local inflammation
      (expression of macrophage chemotactic protein-1; regulated upon activation,
      normal T cell expressed and secreted; cyclooxygenase 2; IL-6; and macrophage
      infiltration) and abolished the expression of PTHrP itself. Moreover, the
      glomerular cell proliferation was hampered, and the healing process was prevented
      on day 7 after venom injection. These results show that PTHrP has antinomic
      actions in glomerulonephritis, participating in both the proinflammatory
      condition and the healing process. Our work reveals the essential role of PTHrP
      in early glomerular repair in an experimental model of glomerulonephritis.

PMID- 29353061
TI  - Next-Generation Sequencing to Detect Deletion of RB1 and ERBB4 Genes in
      Chromophobe Renal Cell Carcinoma: A Potential Role in Distinguishing Chromophobe
      Renal Cell Carcinoma from Renal Oncocytoma.
AB  - Overlapping morphologic, immunohistochemical, and ultrastructural features make
      it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal
      oncocytoma (RO). Because ChRCC is a malignant tumor, whereas RO is a tumor with
      benign behavior, it is important to distinguish these two entities. We aimed to
      identify genetic markers that distinguish ChRCC from RO by using next-generation
      sequencing (NGS). NGS for hotspot mutations or gene copy number changes was
      performed on 12 renal neoplasms, including seven ChRCC and five RO cases. Matched
      normal tissues from the same patients were used to exclude germline variants.
      Rare hotspot mutations were found in cancer-critical genes (TP53 and PIK3CA) in
      ChRCC but not RO. The NGS gene copy number analysis revealed multiple
      abnormalities. The two most common deletions were tumor-suppressor genes RB1 and
      ERBB4 in ChRCC but not RO. Fluorescence in situ hybridization was performed on 65
      cases (ChRCC, n = 33; RO, n = 32) to verify hemizygous deletion of RB1 (17/33,
      52%) or ERBB4 (11/33, 33%) in ChRCC, but not in RO (0/32, 0%). In total, ChRCCs
      (23/33, 70%) carry either a hemizygous deletion of RB1 or ERBB4. The combined use
      of RB1 and ERBB4 fluorescence in situ hybridization to detect deletion of these
      genes may offer a highly sensitive and specific assay to distinguish ChRCC from
      RO.

PMID- 29353062
TI  - miRNA in Rat Liver Sinusoidal Endothelial Cells and Hepatocytes and Application
      to Circulating Biomarkers that Discern Pathogenesis of Liver Injuries.
AB  - Sinusoidal obstruction syndrome is a serious liver injury caused by toxic injury
      to liver sinusoidal endothelial cells (LSECs) during clinical chemotherapy.
      Although circulating miRNAs, such as hepatocyte-specific miR-122-5p and miR-192
      5p, have been proposed as potential noninvasive biomarkers of hepatocellular
      liver injury, these miRNAs may not be specific to damage to other hepatic cell
      types, including LSECs. We characterized miRNA expression in LSECs and
      hepatocytes and investigated whether cell type-specific miRNAs in plasma can
      discern pathogenesis of liver injuries in rats. Comprehensive miRNA expression
      analyses found that 66 and 12 miRNAs were highly expressed in LSECs and
      hepatocytes isolated from nontreated rats, respectively. An LSEC-enriched miR-511
      3p was relatively liver specific according to public data. For establishing LSEC
      and hepatocyte injury models, rats were orally treated with monocrotaline and
      thioacetamide, respectively. In monocrotaline-treated rats, a sinusoidal
      obstruction syndrome model, LSEC damage was observed 6 hours after dosing,
      whereas hepatocellular damage was observed after 48 hours. Interestingly, the
      level of miR-511-3p in plasma was increased as early as 6 hours after
      monocrotaline dosing, followed by an increase of miR-122-5p after 24 hours. In
      the thioacetamide-induced hepatocellular injury model, the level of miR-511-3p
      was not altered in plasma, whereas miR-122-5p levels were increased after 6
      hours. In conclusion, we identified miR-511-3p in plasma as a possible biomarker
      for LSEC damage.

PMID- 29353063
TI  - Dipeptidyl peptidase IV, which probably plays important roles in Alzheimer
      disease (AD) pathology, is upregulated in AD brain neurons and associates with
      amyloid plaques.
AB  - There is evidence from in vitro experiments that dipeptidyl peptidase IV (DPP IV)
      might play role(s) in amyloid formation. However, nothing is known about the
      localization of the enzyme in brains of individuals with Alzheimer's disease. We
      herein show that in comparison to non-demented controls DPP IV is upregulated in
      AD brain neurons and occurs in multiple amyloid plaques.

PMID- 29353064
TI  - Multiplexed isothermal nucleic acid amplification.
AB  - Multiplexed isothermal amplification and detection of nucleic acid sequences and
      biomarkers is of increasing importance in diverse areas including advanced
      diagnostics, food quality control and environmental monitoring. Whilst there are
      several very elegant isothermal amplification approaches, multiplexed
      amplification remains a challenge, requiring careful experimental design and
      optimisation, from judicious primer design in order to avoid the formation of
      primer dimers and non-specific amplification, applied temperature as well as the
      ratio and concentration of primers. In this review, we describe the various
      approaches that have been reported to date for multiplexed isothermal
      amplification, for both "one-pot" multiplexing as well as parallelised
      multiplexing using loop-mediated isothermal amplification, strand-displacement
      amplification, helicase-dependent amplification, rolling circle amplification,
      nucleic acid sequence-based amplification, with a particular focus on recombinase
      polymerase amplification.

PMID- 29353065
TI  - Detection of protein targets with a single binding epitope using DNA-templated
      photo-crosslinking and strand displacement.
AB  - DNA-based probes are powerful analytical tools for protein detection and
      analysis. Target-induced DNA assembly is a widely used strategy to transduce
      target-ligand binding to detectable signals. However, most of the existing
      methods based on DNA assembly require two or more binding sites on the target
      protein. Here we report a novel detection method suitable for protein targets
      with just a single binding site. This method is based on target-induced probe
      assembly, DNA-templated photo-crosslinking, and DNA-mediated toehold strand
      displacement to form a tri-probe complex that is specific for target protein.

PMID- 29353066
TI  - Azodicarbonamide (ADCA): A reconsideration of classification as a respiratory
      sensitiser.

PMID- 29353067
TI  - Antinociception of the spirocyclopiperazinium salt compound LXM-15 via activating
      alpha7 nAChR and M4 mAChR and inhibiting CaMKIIalpha/cAMP/CREB/CGRP signalling
      pathway in mice.
AB  - The aim of this study was to investigate the analgesic effect of the
      spirocyclopiperazinium salt compound LXM-15 by intragastric administration in
      thermal and chemical pain models and further to elucidate the possible molecular
      mechanisms. The results showed that LXM-15 exerted significant antinociception in
      hot-plate test, formalin test and acetic acid writhing test. Western blot
      analysis showed that LXM-15 significantly reduced the upregulation of
      phosphorylation of calcium/calmodulin -dependent protein kinase IIalpha
      (CaMKIIalpha) and cAMP response element-binding protein (CREB), and further
      decreased the elevation of calcitonin gene related peptide (CGRP) in the dorsal
      root ganglion (DRG) and spinal cord in mice. ELISA analysis showed the level of
      cAMP in the spinal cord was decreased by LXM-15. All effects of LXM-15 could be
      blocked by methyllycaconitine citrate (MLA, a selective alpha7 nicotinic receptor
      antagonist) or tropicamide (TRO, a selective M4 muscarinic receptor antagonist).
      This study first reported that intragastric administration of LXM-15 produced
      significant analgesic effect, which may be related to the activation of alpha7
      nicotinic acetylcholine receptor and M4 muscarine acetylcholine receptor, and
      thereby inhibiting CaMKIIalpha/cAMP/CREB/CGRP signalling pathway.

PMID- 29353068
TI  - Mitochondrial ATP-sensitive potassium channel regulates mitochondrial dynamics to
      participate in neurodegeneration of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common age-related neurodegenerative
      disease. Mitochondrial dysfunction has been the focus of the pathogenesis of PD.
      The mitochondrial ATP-sensitive potassium channel (mitoKATP) plays a significant
      role in mitochondrial physiology and has been extensively shown to protect
      against ischemic and brain reperfusion injury. However, there have long been
      controversies regarding its role in Parkinson's disease. We investigated the role
      of mitoKATP channels in rotenone-induced PD model in vivo and vitro and the
      interactions of mitoKATP channels, mitochondrial dynamics and PD. The results
      indicated that the use of diazoxide to activate mitoKATP channels resulted in the
      aggravation of rotenone-induced dopamine neurodegeneration in PC12 cells and SD
      rats. In contrast, the use of 5-hydroxydecanoate (5-HD) to inhibit mitoKATP
      channels improved rotenone-induced dopamine neurodegeneration, which was not
      consistent with mitoKATP channels in ischemic and brain reperfusion injury.
      Further analysis determined that the mitoKATP channel was involved in PD mainly
      via the regulation of mitochondrial biogenesis and fission/fusion. And the pore
      subunits of Kir6.1, the major component of mitoKATP channels, was the key
      contributor in its interaction with mitochondrial dynamics in rotenone-induced
      dopamine neurodegeneration. Therefore, it can be concluded that mitoKATP channels
      regulate mitochondrial dynamics to participate in rotenone-induced PD mainly
      attributes to the pore subunits of Kir6.1. And additionally, though mitoKATP
      channels may represent a direction of one potential target for neuroprotection,
      it should be noted that the effects are different in the activation or inhibition
      of mitoKATP channels in different models.

PMID- 29353069
TI  - Lanthanum chloride impairs memory in rats by disturbing the glutamate-glutamine
      cycle and over-activating NMDA receptors.
AB  - Studies have reported that lanthanum chloride (LaCl3) can across the blood-brain
      barrier, accumulate in the brain and affect the spatial learning and memory
      abilities. However, the potential mechanism that LaCl3-induced neurotoxic effects
      has not yet been defined. Glutamate (Glu) is a vital excitatory neurotransmitter,
      and the excessive Glu accumulation in extracellular space can induce excitatory
      neurotoxicity. This study was designed to research the influence of LaCl3 on the
      spatial learning and memory abilities of rats and to discuss the possible
      mechanism underlying this effect regarding the extracellular Glu concentration,
      the Glu-glutamine (Gln) cycle and the N-methyl-D-aspartate (NMDA) receptors. Four
      groups of Wistar rats were exposed to 0%, 0.125%, 0.25% or 0.5% LaCl3 via the
      drinking water from the day of conception to 1 month after weaning. These results
      showed that LaCl3 exposure damaged spatial learning and memory, long-term
      potentiation, and neuronal ultrastructure, generated an excessive accumulation of
      glutamate, significantly decreased the expression of glutamate/aspartate
      transporter (GLAST), glutamate transporter-1 (GLT-1), glutamine synthetase (GS)
      and phosphate-activated glutaminase (PAG), and increased the expression of GluN1,
      GluN2A and GluN2B. This study showed that LaCl3 impaired the rats' spatial
      learning and memory abilities by disturbing the Glu-Gln cycle and over-activating
      NMDA receptors thereby inducing excitotoxicity.

PMID- 29353070
TI  - 7-Hydroxylation of warfarin is strongly inhibited by sesamin, but not by
      episesamin, caffeic and ferulic acids in human hepatic microsomes.
AB  - Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin.
      Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and
      thus, influences determination of warfarin dosage. A number of factors including
      dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate
      the activity of CYP2C9. The present study tested the hypothesis that sesamin,
      episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7
      hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on
      hepatic microsomes from human donors. It was demonstrated that the rate of 7
      hydroxylation of warfarin was significantly decreased in the presence of sesamin
      in the range of concentrations from 5 to 500 nM, and was not affected by
      episesamin, caffeic acid and ferulic acid in the same range of concentrations.
      The kinetic analysis indicated non-competitive type of inhibition by sesamin with
      Ki = 202 +/- 18 nM. In conclusion, the results of our in vitro study revealed
      that sesamin was able to inhibit formation of a major metabolite of warfarin, 7
      hydroxywarfarin. The potentially negative consequences of the consumption of high
      amounts of sesamin-containing food or dietary supplements in warfarin-treated
      patients need to be further studied.

PMID- 29353071
TI  - Effects of warfarin on biological processes other than haemostasis: A review.
AB  - Warfarin is the world's most widely used anticoagulant drug. Its anticoagulant
      activity is based on the inhibition of the vitamin K-dependent (VKD) step in the
      complete synthesis of a number of blood coagulation factors that are required for
      normal blood coagulation. Warfarin also affects synthesis of VKD proteins not
      related to haemostasis including those involved in bone growth and vascular
      calcification. Antithrombotic activity of warfarin is considered responsible for
      some aspects of its anti-tumour activity of warfarin. Some aspects of activities
      against tumours seem not to be related to haemostasis and included effects of
      warfarin on non-haemostatic VKD proteins as well as those not related to VKD
      proteins. Inflammatory/immunomodulatory effects of warfarin indicate much broader
      potential of action of this drug both in physiological and pathological
      processes. This review provides an overview of the published data dealing with
      the effects of warfarin on biological processes other than haemostasis.

PMID- 29353073
TI  - Serum HBV DNA plus RNA shows superiority in reflecting the activity of
      intrahepatic cccDNA in treatment-naive HBV-infected individuals.
AB  - BACKGROUND: Both serum hepatitis B virus (HBV) DNA and RNA can reflect
      intrahepatic covalently closed circular DNA (cccDNA) activity. However,
      correlations among viral markers haven't been fully explored. OBJECTIVES: Here we
      investigated the correlations between serum HBV RNA and other viral markers in
      acute hepatitis B patients and treatment-naive chronic HBV-infected individuals.
      STUDY DESIGN: The serum viral markers of 19 acute hepatitis B patients and 84
      treatment-naive chronic HBV-infected individuals at different infection stages
      were quantified. Correlations among viral markers were analyzed by Pearson's or
      Spearman's correlation analysis. RESULTS: Serum viral markers and intrahepatic
      cccDNA levels were lower in acute hepatitis B patients than in treatment-naive
      chronic HBV-infected individuals. Serum HBV RNA levels were positively correlated
      with serum HBV DNA, HBsAg and intrahepatic cccDNA levels in HBeAg-positive
      chronic HBV-infected individuals. Total serum HBV nucleic acids (HBV DNA plus
      RNA) showed superiority in reflecting intrahepatic cccDNA activity. Stratified
      analysis revealed that such correlations were only found in HBeAg-positive
      chronic hepatitis B phase. Moreover, high-frequency R193M and P196A mutations
      were found in the RT region of HBV polymerase leading to lower serum HBV DNA and
      higher serum HBV RNA levels in HBeAg-negative chronic HBV infection phase.
      CONCLUSIONS: HBV replication capability was lower in acute hepatitis B patients
      than in chronic HBV-infected individuals. In treatment-naive HBeAg-positive
      chronic HBV-infected individuals, serum HBV DNA plus RNA showed superiority in
      reflecting intrahepatic cccDNA activity than each alone. Moreover, mutated RT
      region of HBV polymerase might lead to the attenuated reverse transcriptional
      activity of HBV polymerase in HBeAg-negative chronic HBV infection phase.

PMID- 29353072
TI  - Development of subcortical volumes across adolescence in males and females: A
      multisample study of longitudinal changes.
AB  - The developmental patterns of subcortical brain volumes in males and females
      observed in previous studies have been inconsistent. To help resolve these
      discrepancies, we examined developmental trajectories using three independent
      longitudinal samples of participants in the age-span of 8-22 years (total 216
      participants and 467 scans). These datasets, including Pittsburgh (PIT;
      University of Pittsburgh, USA), NeuroCognitive Development (NCD; University of
      Oslo, Norway), and Orygen Adolescent Development Study (OADS; The University of
      Melbourne, Australia), span three countries and were analyzed together and in
      parallel using mixed-effects modeling with both generalized additive models and
      general linear models. For all regions and across all samples, males were found
      to have significantly larger volumes as compared to females, and significant sex
      differences were seen in age trajectories over time. However, direct comparison
      of sample trajectories and sex differences identified within samples were not
      consistent. The trajectories for the amygdala, putamen, and nucleus accumbens
      were most consistent between the three samples. Our results suggest that even
      after using similar preprocessing and analytic techniques, additional factors,
      such as image acquisition or sample composition may contribute to some of the
      discrepancies in sex specific patterns in subcortical brain changes across
      adolescence, and highlight region-specific variations in congruency of
      developmental trajectories.

PMID- 29353074
TI  - Diagnostic value of human papillomavirus (HPV) 16 and HPV18 viral loads for the
      detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a cohort of
      African women living with HIV.
AB  - BACKGROUND: African women living with HIV (WLHIV) are at high risk of cervical
      cancer but rarely adequately screened. Better strategies enabling identification
      of WLHIV with high-grade cervical intraepithelial lesions (CIN2+) are required.
      OBJECTIVES: To investigate the diagnostic value of HPV16 and HPV18 viral loads in
      a cohort of African WLHIV. DESIGN: HPV16 and HPV18 viral loads were determined by
      quantitation of the E6 gene DNA by real-time PCR in cervical specimens collected
      at baseline and endline (16 months) from 245 African WLHIV positive for HPV16
      or/and HPV18. Cervical biopsies were graded using the histopathological CIN
      classification. RESULTS: Women with CIN2+ had higher viral load for HPV16 (p <
      0.0001) or HPV18 (p = 0.03) than those without CIN2+. HPV16 viral load >=3.59 log
      copies/1000 cells detected CIN2+ with sensitivity and specificity of 93.5%
      (95%CI: 81.7-98.3%) and 74.1% (95%CI: 66.3-80.6%), respectively, whereas HPV18
      viral load >=1.63 log copies/1000 cells detected CIN2+ with sensitivity and
      specificity of 59.1% (95%CI: 38.7-76.7%) and 66.9% (95%CI: 58.8-74.1%),
      respectively. A high baseline HPV16 viral load was significantly associated with
      persistence of, or progression to CIN2+ at endline; these findings were not
      observed for HPV18. CONCLUSIONS: HPV16 viral load is a powerful marker of CIN2+
      in African WLHIV. HPV18 viral load is of lower diagnostic value in this
      population.

PMID- 29353076
TI  - First report of an Escherichia coli from Lebanon carrying an OXA-181
      carbapenemase resistance determinant.

PMID- 29353075
TI  - BTLA marks a less cytotoxic T-cell subset in diffuse large B-cell lymphoma with
      high expression of checkpoints.
AB  - Immunotherapy results in lymphoma have been encouraging. Preclinical and clinical
      trials have proven checkpoint blockade, such as PD-1 antibody, as an effective
      treatment for lymphoma, including diffuse large B-cell lymphoma (DLBCL).
      Combination of checkpoint blockades has emerged as a new way to treat lymphoma;
      however, the status of checkpoint expression and their function in DLBCL have not
      been fully elucidated yet. In this study, we examined the expression of BTLA, PD
      1, TIM-3, LIGHT, and LAG-3 in tumor microenvironmental T cells of DLBCL using
      flow cytometry and compared the cytotoxicity and differentiation status of BTLA+
      and BTLA- T-cells. We further characterized the relationship of STAT3
      phosphorylation (p-STAT3) with BTLA expression. Our results suggest that BTLA+ T
      cells highly express other checkpoint molecules, including PD-1, TIM-3, LIGHT,
      and LAG-3. Moreover, high expression of BTLA is correlated with advanced stage of
      DLBCL. BTLA+ T cells have a less-differentiated phenotype, lower cytolytic
      function, and higher potential to proliferate compared with BTLA- T cells. Taken
      together, our data provide the first evidence that increased BTLA predicts poor
      prognosis in patients with DLBCL, and blockade of BTLA with other checkpoints may
      potentially represent a new strategy for immunotherapy of DLBCL.

PMID- 29353077
TI  - Classification of heterogeneous genetic variations of microRNA regulome in
      cancer.
AB  - Genetic variations and differential expression of miRNA regulome components are
      associated with cancer. Thus miRNA based diagnosis and treatments have been
      proposed. However, to better explore these options, the molecular changes in
      miRNA regulome must be understood. MicroRNAs can be involved in regulation of
      oncogenes and tumour suppressors. As each miRNA targets broad range of genes,
      minor changes in miRNAs can have great effects, contributing to cell
      transformation. Many genetic variants of miRNA regulome have been reported to be
      associated with cancer, but this information needs to be systematized. Therefore,
      we here classify different types of genetic variations of miRNA regulome in
      cancer. Genetic variations are comprised of structural and short polymorphisms
      and changes in epigenetic landscape. Additionally, unexplained differential
      expression is often reported. These alterations affect miRNA genes and their
      regulatory elements, processing machinery, degradation machinery, and targets,
      leading to changes in miRNA silencing. However, miRNA regulome components are not
      equally explored. A systematic overview over miRNA regulome can contribute to
      more targeted study design and understanding of miRNA function. We also present
      treatments and diagnosis based on miRNA regulome genetic variability and
      expression.

PMID- 29353078
TI  - Blood biochemical parameters and melanomacrophage centers in Nile tilapia fed
      essential oils of clove basil and ginger.
AB  - Nile tilapia (Oreochromis niloticus) is the most farmed freshwater fish in the
      world, however, disease outbreaks are the main cause of losses in production. Due
      to this, there is an increasing interest in natural products for enhancing
      disease resistance, without causing physiological impairment. The aim of this
      study was to verify the effect of the essential oils of clove basil (Ocimum
      gratissimum) and ginger (Zingiber officinale) on physiological and immunological
      parameters of nile tilapia. After 35 and 55 days of supplementation (0.5%, 1.0%
      and 1.5%), blood collection was performed for determination of metabolites
      (glucose, cholesterol, triglycerides, serum total protein and immunoglobulins)
      and lysozyme activity. Spleen tissue was also collected at 55 days for analyzing
      melanomacrophages centers. At 35 days, cholesterol showed significant reduction
      in the treatments 0.5% and 1.5 ginger and 1.5% clove basil. The serum
      triglycerides showed significant reduction in these same treatments, in addition
      to 1.0% clove basil. At 55 days all the supplemented groups showed significant
      reduction for both parameters. The lysozyme activity at 35 days was significantly
      higher in fish supplemented with 1.0% ginger and showed no difference among the
      treatments at 55 days. Regarding the melanomacrophage centers, at 35 days
      increased number in fish supplemented with 0.5% clove basil was observed but with
      no significant difference in the total percent area of spleen occupied by
      centers. The levels of glucose, total serum protein and immunoglobulins did not
      show significant differences in both sampling times. The addition of essential
      oils showed to be useful for improving physiological status of the fish, without
      excessive activation of defense mechanisms.

PMID- 29353079
TI  - Expression and functional characterization of transferrin in Nile tilapia
      (Oreochromis niloticus) in response to bacterial infection.
AB  - Transferrin (TF), an iron-binding glycoprotein, plays an important role in host
      defense against pathogenic infection, which inhibits the growth and proliferation
      of pathogens, deprives iron from invading pathogens, and activates anti-microbial
      responses in macrophages. In this study, a TF homologue (OnTF) was identified
      from Nile tilapia (Oreochromis niloticus) and characterized at expression pattern
      against bacterial infection and capability binding bacterial pathogens. The open
      reading frame of OnTF is 2118 bp of nucleotide sequence encoding polypeptides of
      705 amino acids. The deduced protein is highly homology to the other species,
      containing two conserved iron binding lobes: N-lobe and C-lobe. Expression
      analysis revealed that the OnTF was extremely highly expressed in liver tissue;
      however, much weakly exhibited in other examined tissues including spleen and
      head kidney. The OnTF expression was significantly up-regulated in the liver,
      spleen and head kidney following infection of a Gram-positive bacterial pathogen
      (Streptococcus agalactiae) and a Gram-negative bacterial pathogen (Aeromonas
      hydrophila). The up-regulation of OnTF expression was also demonstrated in
      hepatocytes and macrophages in vitro stimulated with S. agalactiae and A.
      hydrophila. In addition, recombinant OnTF ((r)OnTF) protein possessed capability
      to bind both S. agalactiae and A. hydrophila in vitro. Taken together, the
      present study indicated that OnTF might be involved in host defense against
      bacterial infection in Nile tilapia.

PMID- 29353080
TI  - Atlantic salmon adapted to seawater for 9 weeks develop a robust immune response
      to salmonid alphavirus upon bath challenge.
AB  - Pancreas disease (PD) caused by salmonid alphavirus (SAV) is the most serious
      viral disease in Norwegian aquaculture. Study of the immune response to SAV will
      aid preventative measures including vaccine development. The innate immune
      response was studied in Atlantic salmon infected by either bath immersion (BI) or
      by intra-muscular (i.m.) injection (IM) with SAV subtype 3, two and nine weeks
      after seawater transfer (Phases A and B respectively). Phase A results have been
      previously published (Moore et al., 2017) and Phase B results are presented here
      together with a comparison of results achieved in Phase A. There was a rapid
      accumulation of infected fish in the IM-B (IM Phase B) group and all fish sampled
      were SAV RNA positive by 7 dpi (days post infection). In contrast, only a few SAV
      RNA positive (infected) fish were identified at 14, 21 and 28 dpi in the BI-B (BI
      Phase B) group. Differences in the transcription of several immune genes were
      apparent when compared between the infected fish in the IM-B and BI-B groups.
      Transcription of the analysed genes peaked at 7 dpi in the IM-B group and at 14
      dpi in the BI-B group. However, this latter finding was difficult to interpret
      due to the low prevalence of SAV positive fish in this group. Additionally, fish
      positive for SAV RNA in the BI-B group showed higher transcription of IL-1beta,
      IFNgamma and CXCL11_L1, all genes associated with the inflammatory response,
      compared to the IM-B group. Histopathological changes in the heart were
      restricted to the IM-B group, while (immune) cell filtration into the pancreas
      was observed in both groups. Compared to the Phase A fish that were exposed to
      SAV3 two weeks after seawater transfer, the Phase B fish in the current paper,
      showed a higher and more sustained innate immune gene transcription in response
      to the SAV3 infection. In addition, the basal transcription of several innate
      immune genes in non-infected control fish in Phase B (CT-B) was also
      significantly different when compared to Phase A control fish (CT-A).

PMID- 29353081
TI  - Hydrogels based on poly(methyl vinyl ether-co-maleic acid) and Tween 85 for
      sustained delivery of hydrophobic drugs.
AB  - Hydrogels based on poly(methyl vinyl ether-co-maleic acid) and Tween 85 were
      prepared for hydrophobic drug delivery. The hydrogels were synthesized following
      a simple procedure carried out in solid state. The process did not require the
      use of any solvent and, as it is based on an esterification reaction, no toxic by
      products were obtained. The resulting hydrogels contained Tween 85 inside the
      structure and due to the amphiphilic nature of this compound, hydrophobic domains
      within the hydrogel structure were formed. The obtained hydrogels showed good
      swelling capacities ranging from 100% to 600%. The esterification reaction that
      took place between poly(methyl vinyl ether-co-maleic acid) and Tween 85 was
      confirmed by infrared spectroscopy. Hydrogels were loaded with a hydrophobic drug
      model, Curcumin (CUR), showing that the hydrogels were able to retain up to 36 mg
      of CUR per g of hydrogel. Additionally, the synthesized hydrogels provided in
      vitro sustained CUR release over periods of up to 30 days. Finally, and due to
      the mucoadhesive nature of the prepared materials, one of the hydrogels was
      tested in vitro as an oral drug delivery system. For this purpose, the selected
      material was milled into microparticles (45-90 um diameter). The release of CUR
      from the microparticles was evaluated under simulated gastric and intestinal
      conditions. The microparticles were able to release their cargos in 7 h. However,
      further work is required to optimize this system for oral drug delivery
      applications.

PMID- 29353082
TI  - 3D extrusion printing of high drug loading immediate release paracetamol tablets.
AB  - The manufacture of immediate release high drug loading paracetamol oral tablets
      was achieved using an extrusion based 3D printer from a premixed water based
      paste formulation. The 3D printed tablets demonstrate that a very high drug
      (paracetamol) loading formulation (80% w/w) can be printed as an acceptable
      tablet using a method suitable for personalisation and distributed manufacture.
      Paracetamol is an example of a drug whose physical form can present challenges to
      traditional powder compression tableting. Printing avoids these issues and
      facilitates the relatively high drug loading. The 3D printed tablets were
      evaluated for physical and mechanical properties including weight variation,
      friability, breaking force, disintegration time, and dimensions and were within
      acceptable range as defined by the international standards stated in the United
      States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify
      the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance
      Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning
      calorimetry (DSC) were used to assess possible drug-excipient interactions. The
      3D printed tablets were evaluated for drug release using a USP dissolution
      testing type I apparatus. The tablets showed a profile characteristic of the
      immediate release profile as intended based upon the active/excipient ratio used
      with disintegration in less than 60 s and release of most of the drug within 5
      min. The results demonstrate the capability of 3D extrusion based printing to
      produce acceptable high-drug loading tablets from approved materials that comply
      with current USP standards.

PMID- 29353083
TI  - Combining ultrasound and intratumoral administration of doxorubicin-loaded
      microspheres to enhance tumor cell killing.
AB  - Melanoma is an incurable disease for which alternative treatments to chemotherapy
      alone are sought. Here, using a melanoma model, we investigated the antitumor
      potential of combining ultrasound (US) with poly(lactic-co-glycolic acid) (PLGA)
      microspheres loaded with doxorubicin (DOX). The aim was to achieve synergistic
      tumoricidal activity through direct and indirect US-mediated damage of tumor
      cells combined with sustained and potentially controllable release (when combined
      with US) of DOX from microspheres. An in vitro release assay demonstrated an
      ability of US to affect the release kinetics of DOX from DOX-loaded PLGA
      microspheres by inducing a 12% increase in the rate of release. In vitro
      viability assays demonstrated that combining US with DOX-loaded PLGA microspheres
      resulted in synergistic tumor cell (B16-F10 melanoma cells) killing. Melanoma
      bearing mice were treated intratumorally with DOX (8 ug)-loaded microspheres and
      subjected to US treatment at the tumor site. This treatment could significantly
      extend survival (mean survival (MS) = 22.1 days) compared to untreated mice (MS =
      10.4 days) and most other treatments, such as blank microspheres plus US (MS =
      11.5 days) and DOX (8 ug)-loaded microspheres alone (MS = 13 days). The findings
      that immune checkpoint blockade did not significantly extend survival of mice
      treated with DOX (8 ug)-loaded microspheres plus US, and that tumor-free
      ("cured") mice were not protected from subsequent tumor rechallenge suggests
      minimal involvement of the adaptive immune response in the observed antitumor
      activity. Nevertheless, the synergistic increase in survival of melanoma
      challenged mice treated with the combination of US and DOX-loaded microspheres
      implicates such a treatment methodology as a promising additional tool for
      combatting otherwise currently incurable cancers.

PMID- 29353084
TI  - Creating diverse synapses from the same molecules.
AB  - Research over the past half a century has revealed remarkable diversity among
      chemical synapses of the CNS. The structural, functional and molecular diversity
      of synapses was mainly concluded from studying different synapses in distinct
      brain regions and preparations. It is not surprising that synapses made by
      molecularly distinct pre-synaptic and post-synaptic cells display different
      morphological and functional properties with distinct underlying molecular
      mechanisms. However, synapses made by a single presynaptic cell onto distinct
      types of postsynaptic cells, or distinct presynaptic inputs onto a single
      postsynaptic cell, also show remarkable heterogeneity. Here, by reviewing recent
      experiments, I suggest that robust functional diversity can be achieved by
      building synapses from the same molecules, but using different numbers, densities
      and nanoscale arrangements.

PMID- 29353085
TI  - Reactions of a tetranuclear Pt-thiosemicarbazone complex with model proteins.
AB  - The tetranuclear Pt complex (PtL)4 (where L2- is the anion derived from para
      isopropyl thiosemicarbazone) was first described in A.G. Quiroga et al., J. Med.
      Chem. 41, 1998, 1399-1408. (PtL)4 manifests antiproliferative properties toward
      various cancer cell lines being a promising anticancer drug candidate. Yet,
      details of its reactivity with biomolecules have not been elucidated. To this
      end, we investigated the reactions of (PtL)4 with a few model proteins, i.e.
      bovine pancreatic ribonuclease (RNase A), cytochrome c (Cyt c) and hen egg white
      lysozyme (Lysozyme), through electrospray ionization mass spectrometry and other
      biophysical methods. A rich reactivity of (PtL)4 with the above-mentioned model
      proteins is observed, leading to the formation of numerous metallodrug-protein
      adducts. The tetranuclear complex breaks down and various fragments bind proteins
      up to high metal/protein ratios; this typically results into very complicated
      mass spectral patterns. However, some of the main mass peaks could be assigned in
      the case of the Lysozyme adduct. In addition, crystallographic data were obtained
      for the (PtL)4/Lysozyme and (PtL)4/RNase A adducts pointing at His side chains as
      the primary binding sites for monometallic Pt fragments. Notably, a few selected
      features of the interactions observed in the (PtL)4/protein adducts were
      reproduced by reacting (PtL)4 with a small molecule, i.e. N-methylimidazole. In
      conclusion, the present study confirms the prodrug nature of the tetraplatinum
      complex, clarifies one possible pathway for its activation through cluster
      disassembly and allows initial identification of adducts formed with a
      representative protein.

PMID- 29353086
TI  - Ruthenium dendrimers as carriers for anticancer siRNA.
AB  - Dendrimers, which are considered as one of the most promising tools in the field
      of nanobiotechnology due to their structural organization, showed a great
      potential in gene therapy, drug delivery, medical imaging and as antimicrobial
      and antiviral agents. This article is devoted to study interactions between new
      carbosilane-based metallodendrimers containing ruthenium and anti-cancer small
      interfering RNA (siRNA). Formation of complexes between anti-cancer siRNAs and Ru
      based carbosilane dendrimers was evaluated by transmission electron microscopy,
      circular dichroism and fluorescence. The zeta-potential and the size of
      dendriplexes were determined by dynamic light scattering. The internalization of
      dendriplexes were estimated using HL-60 cells. Results show that ruthenium
      dendrimers associated with anticancer siRNA have the ability to deliver siRNA as
      non-viral vectors into the cancer cells. Moreover, dendrimers can protect siRNA
      against nuclease degradation. Nevertheless, further research need to be performed
      to examine the therapeutic potential of ruthenium dendrimers as well as
      dendrimers complexed with siRNA and anticancer drugs towards cancer cells.

PMID- 29353087
TI  - The impact of timetable changes on student achievement and learning experiences.
AB  - BACKGROUND: Many pre-registration nursing programs in Australia use distributive
      models of clinical placement whereby students attend placement on regular days
      each week of the teaching semester. The use of this model offers practical
      advantages by increasing the placement offerings, but reduces the weekdays
      available for students to attend on-campus classes. The impact of introducing
      this model on the delivery of on-campus classes has not been examined.
      OBJECTIVES: The aim of this study was to explore the impact of delivering classes
      using a condensed weekly timetable on the academic achievement, learning
      experiences and approaches to learning of pre-registration Bachelor of Nursing
      Science students at an Australian regional university. METHODS: This was a mixed
      methods study, including Likert-type and free text responses. Second-year
      students studying Human Pathophysiology and Pharmacology were invited to complete
      a questionnaire about their learning practices and experiences; student grades
      were obtained from official university records. RESULTS: The academic achievement
      of students learning under the condensed class schedule was approximately 7.5%
      lower than that achieved by cohorts prior to the timetable changes. This resulted
      in an additional 9% of the cohort failing the subject compared to previous
      cohorts. Many students reported that they did not prepare adequately for classes
      and that their learning experiences were negatively impacted by the condensed
      class timetable. CONCLUSIONS: The incorporation of a distributed model for
      clinical placements required major changes to the delivery of on-campus
      coursework classes and added to the semester workload for some Nursing Science
      students. These changes coincided with lower academic achievement by students
      learning Human Pathophysiology and Pharmacology and poorer quality learning
      experiences. The development of students' awareness of how they study and the
      effectiveness of their study practices may help them to develop self-regulated
      learning skills which will assist them to succeed in diverse learning
      environments and workplaces.

PMID- 29353088
TI  - Healthcare students' evaluation of the clinical learning environment and
      supervision - a cross-sectional study.
AB  - BACKGROUND: The purpose of clinical placements and supervision is to promote the
      development of healthcare students' professional skills. High-quality clinical
      learning environments and supervision were shown to have significant influence on
      healthcare students' professional development. OBJECTIVES: This study aimed to
      describe healthcare students' evaluation of the clinical learning environment and
      supervision, and to identify the factors that affect these. DESIGN: The study was
      performed as a cross-sectional study. METHODS: The data (n = 1973) were gathered
      through an online survey using the Clinical Learning Environment, Supervision and
      Nurse Teacher scale during the academic year 2015-2016 from all healthcare
      students (N = 2500) who completed their clinical placement at a certain
      university hospital in Finland. The data were analysed using descriptive
      statistics and binary logistic regression analysis. RESULTS: More than half of
      the healthcare students had a named supervisor and supervision was completed as
      planned. The students evaluated the clinical learning environment and supervision
      as 'good'. The students' readiness to recommend the unit to other students and
      the frequency of separate private unscheduled sessions with the supervisor were
      the main factors that affect healthcare students' evaluation of the clinical
      learning environment and supervision. Individualized and goal-oriented
      supervision in which the student had a named supervisor and where supervision was
      completed as planned in a positive environment that supported learning had a
      significant impact on student's learning. CONCLUSIONS: The clinical learning
      environment and supervision support the development of future healthcare
      professionals' clinical competence. The supervisory relationship was shown to
      have a significant effect on the outcomes of students' experiences. We recommend
      the planning of educational programmes for supervisors of healthcare students for
      the enhancement of supervisors' pedagogical competencies in supervising students
      in the clinical practice.

PMID- 29353089
TI  - Influence of perceptions and stereotypes of the nursing role on career choice in
      secondary students: A regional perspective.
AB  - BACKGROUND: This study examined the influence that perceptions and stereotypes of
      the nursing role had on future career choice of rural secondary students.
      OBJECTIVE: The study was undertaken to identify a method of attracting final year
      secondary school students to an undergraduate nursing degree at a rural
      University. DESIGN: A mixed method study using a pre-post-interventional design.
      SETTING: The rural campus of an Australian university. PARTICIPANTS: 71 secondary
      students attending a secondary school career development program at a rural
      Australian university. METHOD: Semi structured questionnaires were used for data
      collection. The surveys were analysed using descriptive statistics and content
      analysis of open-ended survey questions. RESULTS: The research supports the
      importance of being aware of young people's impressions about nurses and nursing
      as a career, to ensure the successful implementation of targeted recruitment.
      CONCLUSION: Targeted recruitment strategies can increase students' awareness of
      the wide variety of pathways within nursing, rather than leaving awareness to
      what family, friends or career advisers tell them, or how nurses are portrayed on
      television, movies and the media.

PMID- 29353090
TI  - Investigating the prevalence of febrile convulsion in Kayseri, Turkey: An
      assessment of the risk factors for recurrence of febrile convulsion and for
      development of epilepsy.
AB  - PURPOSE: The purpose of this study was to investigate the prevalence and
      recurrence of febrile convulsion (FC) and risk factors for development of
      epilepsy in school children throughout in the Kayseri provincial center. METHOD:
      Ten thousand individuals selected using "stratified cluster sampling" from a
      student population of 259,428 inside the Kayseri Urban Municipality represented
      the study sample. Fifteen thousand questionnaires were distributed, of which
      10,742 (71.6%) were returned. Telephone interviews were performed with the
      families of the students reported as having undergone FC, and the medical records
      of patients with a history of hospitalization were evaluated. Data were analyzed
      on IBM SPSS Statistics 22.0 package program. Significance was set at p < 0.05.
      RESULTS: Prevalence of FC was 4.2% in girls and 4.3% in boys, with a total
      prevalence of 4.3%. Recurrence of FC was observed in 25.4% of cases. Risk of
      recurrence increased 7.1 times in subjects with a history of FC in first and
      second degree relatives, 17.8 times in those with fever interval <1 h before
      convulsion and 17.6 times in those with pre-convulsion body temperature <39 
      degrees C. Epilepsy developed in 33 (7.2%) cases. Neurodevelopmental abnormality
      was the most important risk factor for epilepsy (21.1-fold risk increase).
      CONCLUSIONS: Analysis revealed that FC with a good prognosis had a high rate of
      recurrence and a higher risk of epilepsy than in the general population. The
      prevalence of FC in the province of Kayseri was closer to that in developed
      rather than developing countries.

PMID- 29353092
TI  - Individual and dyadic rope turning as a window into social coordination.
AB  - The spontaneous and intentional movement coordination between peoples is well
      understood. Less is known about such interactions when the coordination is
      subordinate to the task and when the task involves, next to vision, mechanically
      induced haptic and kinesthetic coupling between dyadic partners. We therefore
      investigated dyadic jump rope turning. Fifteen dyadic pairs conjointly turned a
      jump rope to which five markers were equidistantly attached, and whose movements
      were recorded in 3D. In addition, each participant turned one side of the rope
      while the other side was quasi-fixed in an individual baseline condition. The
      participants' goal was to turn the rope regularly and smoothly. Individual
      spontaneous turning frequencies differed substantially across participants. Yet,
      dyadic pairs spontaneously turned the rope at a common frequency, indicative of
      frequency entrainment. The dyadic rope rotations were less variable despite
      weaker between near-hand marker coordination than the individual rope rotations,
      and the degree of performance improvement was most pronounced for participants
      who were paired with a partner who performed better in the individual condition.
      The direction and relative strength of the coupling between partners varied
      substantially across dyads, but the degree of coupling asymmetry had no
      substantial effect on the rope tuning quality. The absolute degree in which
      dyadic partners adjusted to each other, however, scaled moderately with their
      turning performance. Although the individual performances did not predict the
      dyadic performances, the difference in individual performance between dyadic
      partners had some predictive value for the dyadic performance. In combination,
      these results indicate that the partners were functionally adapting to each other
      in order to satisfy the task goal and suggest that the relative performance
      differences rather than the individual performances has predictive value for
      conjoint action.

PMID- 29353091
TI  - Adding vibrotactile feedback to a myoelectric-controlled hand improves
      performance when online visual feedback is disturbed.
AB  - We investigated whether adding vibrotactile feedback to a myoelectric-controlled
      hand, when visual feedback is disturbed, can improve performance during a
      functional test. For this purpose, able-bodied subjects, activating a myoelectric
      controlled hand attached to their right hand performed the modified Box & Blocks
      test, grasping and manipulating wooden blocks over a partition. This was
      performed in 3 conditions, using a repeated-measures design: in full light, in a
      dark room where visual feedback was disturbed and no auditory feedback - one time
      with the addition of tactile feedback provided during object grasping and
      manipulation, and one time without any tactile feedback. The average time needed
      to transfer one block was measured, and an infrared camera was used to give
      information on the number of grasping errors during performance of the test. Our
      results show that when vibrotactile feedback was provided, performance time was
      reduced significantly, compared with when no vibrotactile feedback was available.
      Furthermore, the accuracy of grasping and manipulation was improved, reflected by
      significantly fewer errors during test performance. In conclusion, adding
      vibrotactile feedback to a myoelectric-controlled hand has positive effects on
      functional performance when visual feedback is disturbed. This may have
      applications to current myoelectric-controlled hands, as adding tactile feedback
      may help prosthesis users to improve their functional ability during daily life
      activities in different environments, particularly when limited visual feedback
      is available or desirable.

PMID- 29353093
TI  - Executive functions, visual-motor coordination, physical fitness and academic
      achievement: Longitudinal relations in typically developing children.
AB  - The present longitudinal study included different school readiness factors
      measured in kindergarten with the aim to predict later academic achievement in
      second grade. Based on data of N = 134 children, the predictive power of
      executive functions, visual-motor coordination and physical fitness on later
      academic achievement was estimated using a latent variable approach. By entering
      all three predictors simultaneously into the model to predict later academic
      achievement, significant effects of executive functions and visual-motor
      coordination on later academic achievement were found. The influence of physical
      fitness was found to be substantial but indirect via executive functions. The
      cognitive stimulation hypothesis as well as the automaticity hypothesis are
      discussed as an explanation for the reported relations.

PMID- 29353094
TI  - Effects of scaling task constraints on emergent behaviours in children's racquet
      sports performance.
AB  - Manipulating task constraints by scaling key features like space and equipment is
      considered an effective method for enhancing performance development and refining
      movement patterns in sport. Despite this, it is currently unclear whether scaled
      manipulation of task constraints would impact emergent movement behaviours in
      young children, affording learners opportunities to develop relevant skills.
      Here, we sought to investigate how scaling task constraints during 8 weeks of
      mini tennis training shaped backhand stroke development. Two groups, control (n =
      8, age = 7.2 +/- 0.6 years) and experimental (n = 8, age 7.4 +/- 0.4 years),
      underwent practice using constraints-based manipulations, with a specific field
      of affordances designed for backhand strokes as the experimental treatment. To
      evaluate intervention effects, pre- and post-test match-play characteristics
      (e.g. forehand and backhand percentage strokes) and measures from a tennis
      specific skills test (e.g. forehand and backhand technical proficiency), were
      evaluated. Post intervention, the experimental group performed a greater
      percentage of backhand strokes out of total number of shots played (46.7 +/-
      3.3%). There was also a significantly greater percentage of backhand winners out
      of total backhand strokes observed (5.5 +/- 3.0%), compared to the control group
      during match-play (backhands = 22.4 +/- 6.5%; backhand winners = 1.0 +/- 3.6%).
      The experimental group also demonstrated improvements in forehand and backhand
      technical proficiency and the ability to maintain a rally with a coach, compared
      to the control group. In conclusion, scaled manipulations implemented here
      elicited more functional performance behaviours than standard Mini Tennis Red
      constraints. Results suggested how human movement scientists may scale task
      constraint manipulations to augment young athletes' performance development.

PMID- 29353095
TI  - Integration of visual feedback and motor learning: Corticospinal vs.
      corticobulbar pathway.
AB  - Although movement is controlled by different descending pathways, it remains
      unknown whether the integration of visual feedback and motor learning differs for
      movements controlled by different descending pathways. Here, we compare motor
      control and learning of the ankle joint and tongue because they are primarily
      controlled by the corticospinal and corticobulbar pathways, respectively. Twelve
      young adults (19.63 +/- 2.11 years, 6 females) practiced a tracking task
      (combination of 0.02, 0.37, 0.5, and 1 Hz) with ankle dorsiflexion and with
      tongue elevation for 100 trials. The participants practiced each effector (ankle
      and tongue) in different days and the order of the effector was counterbalanced.
      Following practice, participants performed the same tracking task with concurrent
      contractions of the tongue and ankle (dual tracking task; transfer) with three
      different visual feedback conditions (no visual feedback, visual feedback only
      for ankle, visual feedback only for tongue). We quantified the force accuracy
      (RMSE) from each effector during the practice and transfer periods. During
      practice, the force accuracy and performance improvement to the visuomotor task
      was greater for the ankle dorsiflexion than tongue elevation. During the transfer
      task, the ankle dorsiflexion was more accurate than tongue elevation, independent
      of whether visual feedback was given for the ankle or tongue. The greater
      performance improvement for the ankle dorsiflexion during practice was related to
      superior transfer performance. These findings suggest that the corticospinal
      pathway integrates visual feedback more efficiently than the corticobulbar
      pathway, which enhances performance and learning of visuomotor tasks.

PMID- 29353096
TI  - Modification of Aspergillus niger by conducting polymer, Polypyrrole, and the
      evaluation of electrochemical properties of modified cells.
AB  - The enhancement of bioelectrochemical properties of microorganism by in situ
      formation of conducting polymer within the cell structures (e.g. cell wall) was
      performed. The synthesis of polypyrrole (Ppy) within fungi (Aspergillus niger)
      cells was achieved. Two different Aspergillus niger strains were selected due to
      their ability to produce glucose oxidase, which initiated the Ppy formation
      through products of enzymatic reaction. The evolution of Ppy structural features
      was investigated by absorption spectroscopy, cyclic voltammetry and Fourier
      transform infrared spectroscopy.

PMID- 29353097
TI  - Genetics of immunoglobulin-A vasculitis (Henoch-Schonlein purpura): An updated
      review.
AB  - Immunoglobulin-A vasculitis (IgAV) is classically a childhood small-sized blood
      vessel vasculitis with predominant involvement of the skin. Gastrointestinal and
      joint manifestations are common in patients diagnosed with this condition.
      Nephritis, which is more severe in adults, constitutes the most feared
      complication of this vasculitis. The molecular bases underlying the origin of
      IgAV have not been completely elucidated. Nevertheless, several pieces of
      evidence support the claim that genes play a crucial role in the pathogenesis of
      this disease. The human leukocyte antigen (HLA) region is, until now, the main
      genetic factor associated with IgAV pathogenesis. Besides a strong association
      with HLA class II alleles, specifically HLA-DRB1 alleles, HLA class I alleles
      also seem to influence on the predisposition of this disease. Other gene
      polymorphisms located outside the HLA region, including those coding cytokines,
      chemokines, adhesion molecules as well as those related to T-cells, aberrant
      glycosylation of IgA1, nitric oxide production, neoangiogenesis, renin
      angiotensin system and lipid, Pyrin and homocysteine metabolism, may be
      implicated not only in the predisposition to IgAV but also in its severity. An
      update of the current knowledge of the genetic component associated with the
      pathogenesis of IgAV is detailed in this review.

PMID- 29353098
TI  - The anti-inflammatory effects of statins on patients with rheumatoid arthritis: A
      systemic review and meta-analysis of 15 randomized controlled trials.
AB  - BACKGROUND: Over the past several years, numerous studies investigated the anti
      inflammatory effects of statin on patients with RA. However, the findings of the
      individual studies were often inconsistent or conflicting. MATERIALS AND METHODS:
      The Pubmed, Web of Science, Embase, Cochrane Library and CNKI literature
      databases were searched in order to identify randomized controlled clinical
      trials where the association between the anti-inflammatory effect of statin and
      RA was investigated. Two researchers performed data extraction from eligible
      independently. Quality parameters and risk of bias in the included studies were
      assessed according to Cochrane's guidelines. The pooled Standardized Mean
      Difference (SMD) with a 95%CI was used to assess the anti-inflammatory effect of
      statin in patients with RA. RESULTS: Fifteen randomized controlled clinical,
      classified as "high quality" and with a relatively low risk of selection bias,
      were included in the meta-analysis. Of these, eight reported that there was no
      difference in the level of serum total lipids between the atorvastatin-treated
      and the conventional treatment group. However, the pooled analysis showed that
      atorvastatin could increase the level of serum amount of high-density lipoprotein
      (HDL) in RA patients by approximately x +/- SD95% [HDL: SMD = 0.807, 95%CI =
      (0.187, 1.426), p = .011]. Meanwhile atorvastatin could reduce the level of serum
      low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride (TG) in
      RA patient by x +/- SD95% [LDL: SMD = -4.015, 95%CI = (-5.848, -2.183), p = .000;
      TC: SMD = -4.497, 95%CI = (-6.457, -2.537), p = .000; TG: SMD = -1.475, 95%CI = (
      2.352, -0.599), p = .001]. Nine studies reported a change in C-Reactive Protein
      (CRP) after atorvastatin treatment, and the pooled analysis showed that
      atorvastatin decreased CRP in RA patients by x +/- SD95% [SMD = -3.033, 95%CI = (
      4.460, -1.606), p = .000]. Seven studies investigated the change of Erythrocyte
      Sedimentation Rate (ESR), and the pooled analysis showed that atorvastatin
      decreased ESR by x +/- SD95% [SMD = -2.097, 95%CI = (-3.408, -0.786), p = .002].
      Nine studies reported the improvement of disease activity score in RA patients
      after taking atorvastatin for 12 weeks, and the pooled analysis showed
      atorvastatin could decrease the DAS28 score in RA patients by x +/- SD95% [SMD = 
      2.001, 95%CI = (-3.191, -0.811), p = .001]. CONCLUSIONS: Statins have a
      significant anti-inflammatory effect in RA patients. However, atorvastatin was
      superior to simvastatin both in terms of its anti-inflammatory and lipid-lowering
      activities.

PMID- 29353099
TI  - Cardiovascular involvement in systemic rheumatic diseases: An integrated view for
      the treating physicians.
AB  - Systemic autoimmune diseases can affect various kinds of organs including the
      kidney, the skin, soft tissue and the bone. Among others, cardiovascular
      involvement in rheumatic diseases has been shown to affect myocardium,
      pericardium, cardiac vessels, conduction system and valves, eventually leading to
      increased mortality. In general, underlying chronic inflammation leads to
      premature atherosclerosis, but also other manifestations such as arrhythmia and
      heart failure may have a 'silent' progress. Traditional cardiovascular risk
      factors play a secondary role, while disease-specific factors (i.e. disease
      duration, severity, antibody positivity, persistent disease activity) can
      directly influence the cardiovascular system. Therefore, early diagnosis is
      critical to optimize management and to control inflammatory activity and recent
      data suggest that risk factors (i.e. hypercholesterolemia and hypertension) need
      intensive treatment as well. With the advent of immunosuppressive agents, most
      rheumatic diseases are well controlled on treatment, but information related to
      their cardioprotective efficacy is not well-defined. In this review, we focus on
      cardiovascular involvement in rheumatic diseases and highlight current evidence
      which should be of help for the treating physicians. Moreover, cardiotoxicity of
      immunosuppressive drugs is a rare issue and such potential adverse events will be
      briefly discussed.

PMID- 29353100
TI  - Vitamin D and juvenile systemic lupus erythematosus: Lights, shadows and still
      unresolved issues.
AB  - Systemic lupus erythematosus (SLE) and juvenile SLE (jSLE) are autoimmune
      disorders naturally associated with several genetic, environmental, hormonal, and
      immunological contributing factors. It has been assumed that vitamin D deficiency
      may have a role in the immune activation of patients with SLE and play an active
      part in many comorbidities and even complications. A host of clinical studies
      suggested that vitamin D exerts inhibitory effects on many immunological
      abnormalities associated with SLE, also in children and adolescents, while
      different reports have hypothesized that vitamin D may be associated with
      accelerated cardiovascular disease in SLE. This review updates and summarizes the
      information related to the immunoregulatory effects of vitamin D and its
      importance in jSLE, discusses the innumerable correlations between vitamin D and
      disease activity, including clinical expression and gene polymorphisms of vitamin
      D receptor as well as the recommendations for vitamin D supplementation in these
      patients. Despite the excitement raised by many data obtained about vitamin D and
      its influence on several aspects of the disease, further well-designed
      perspective trials are required to define the exact role that vitamin D may have
      in the management of both SLE and jSLE.

PMID- 29353101
TI  - Amyloid pathology in the progression to mild cognitive impairment.
AB  - The objective of this study was to determine the cognitive and functional decline
      and development of brain injury in individuals progressing from preclinical (beta
      amyloid positive cognitively normal) to prodromal Alzheimer's disease (AD) (beta
      amyloid positive mild cognitive impairment [MCI]), and compare this with
      individuals who progress to MCI in the absence of significant amyloid pathology.
      Seventy-five cognitively healthy participants who progressed to MCI were followed
      for 4 years on average and up to 10 years. We tested effects of beta-amyloid
      (Abeta) on measures of cognition, functional status, depressive symptoms, and
      brain structure and metabolism. Preclinical AD subjects showed greater cognitive
      decline in multiple domains and increased cerebrospinal fluid phosphorylated tau
      levels at baseline while Abeta-negative progressors showed increased rates of
      white matter hyperintensity accumulation and had a greater frequency of
      depressive symptoms at baseline. Abeta status did not influence patterns of brain
      atrophy, but preclinical AD subjects showed greater decline of brain metabolism
      than Abeta-negative progressors. Several unique features separate the transition
      from preclinical to prodromal AD from other causes of cognitive decline. These
      features may facilitate early diagnosis and treatment of AD, especially in
      clinical trials aimed at halting the progression from preclinical to prodromal
      AD.

PMID- 29353102
TI  - Aging African green monkeys manifest transcriptional, pathological, and cognitive
      hallmarks of human Alzheimer's disease.
AB  - While many preclinical models of Alzheimer's disease (AD) have been reported,
      none fully recapitulate the disease. In an effort to identify an appropriate
      preclinical disease model, we characterized age-related changes in 2 higher order
      species, the African green monkey (AGM) and the rhesus macaque. Gene expression
      profiles in the dorsolateral prefrontal cortex and the visual cortex showed age
      related changes in AGMs that are strikingly reminiscent of AD, whereas aged
      rhesus were most similar to healthy elderly humans. Biochemically, age-related
      changes in AGM cerebrospinal fluid levels of tau, phospho-tau, and amyloid beta
      were consistent with AD. Histologically, aged AGMs displayed pathological
      hallmarks of the disease, plaques, and 2 AGMs showed evidence of neurofibrillary
      tangle-like structures. We hypothesized and confirmed that AGMs have age-related
      cognitive deficits via a prefrontal cortex-dependent cognition test, and that
      symptomatic treatments that improve cognition in AD patients show efficacy in
      AGMs. These data suggest that the AGM could represent a novel and improved
      translational model to assist in the development of therapeutics for AD.

PMID- 29353104
TI  - Galactosylated iodine-based small molecule I.V. CT contrast agent for bile duct
      imaging.
AB  - Computed tomography (CT) with contrast plays an important role as a clinical
      diagnostic tool but still has a limited diagnostic range. In this work, we
      developed a novel injectable iodine-based small molecule CT contrast agent, even
      can be used for bile duct diagnostics. The bile duct diagnosable CT contrast
      agent (BDICA) is synthesized with 5-amino-2,4,6-triiodoisophthaloyl dichloride
      (ATIPC), tromethamine and lactobionic acid (LBA) for asialoglycoprotein receptor
      (ASGPR) targeted delivery via receptor-mediated endocytosis and transport to the
      bile canaliculi. Specific binding to the ASGPRs was confirmed by in vitro
      cellular uptake in HepG2 cells (ASGPR positive) and HCT 116 cells (ASGPR
      negative). Compared to iohexol, BDICA has equal in vivo distribution and a 13
      fold iodine increase in content was observed in bile juice after BDICA injection.
      The radiopaque contrast effect in the bile duct has been clearly shown in in vivo
      CT scans. Furthermore, within 36 h, 91.3% of the BDICA was eliminated without
      organ damage, which verified the overall safety of the contrast agent. BDICA not
      only provides sufficient contrast images similar to iohexol, but also provides
      superior images of the bile duct. Based on recent studies, it has been shown that
      BDICA is a promising, safe and effective contrast agent for CT imaging of the
      organs and soft tissues, including the bile duct.

PMID- 29353103
TI  - Taking the heat or taking the temperature? A qualitative study of a large-scale
      exercise in seeking to measure for improvement, not blame.
AB  - Measurement of quality and safety has an important role in improving healthcare,
      but is susceptible to unintended consequences. One frequently made argument is
      that optimising the benefits from measurement requires controlling the risks of
      blame, but whether it is possible to do this remains unclear. We examined
      responses to a programme known as the NHS Safety Thermometer (NHS-ST). Measuring
      four common patient harms in diverse care settings with the goal of supporting
      local improvement, the programme explicitly eschews a role for blame. The study
      design was ethnographic. We conducted 115 hours of observation across 19 care
      organisations and conducted 126 interviews with frontline staff, senior national
      leaders, experts in the four harms, and the NHS-ST programme leadership and
      development team. We also collected and analysed relevant documents. The
      programme theory of the NHS-ST was based in a logic of measurement for
      improvement: the designers of the programme sought to avoid the appropriation of
      the data for any purpose other than supporting improvement. However,
      organisational participants - both at frontline and senior levels - were
      concerned that the NHS-ST functioned latently as a blame allocation device. These
      perceptions were influenced, first, by field-level logics of accountability and
      managerialism and, second, by specific features of the programme, including
      public reporting, financial incentives, and ambiguities about definitions that
      amplified the concerns. In consequence, organisational participants, while they
      identified some merits of the programme, tended to identify and categorise it as
      another example of performance management, rich in potential for blame. These
      findings indicate that the search to optimise the benefits of measurement by
      controlling the risks of blame remains challenging. They further suggest that a
      well-intentioned programme theory, while necessary, may not be sufficient for
      achieving goals for improvement in healthcare systems dominated by institutional
      logics that run counter to the programme theory.

PMID- 29353107
TI  - An educational intervention to enhance clinical skills learning: Experiences of
      nursing students and teachers.
AB  - The simulation centre is a key setting for the acquisition of practical skills.
      However, pedagogical underpinnings of skills instruction in this setting are not
      always well founded. This study aimed to explore student and teacher experiences
      with an educational intervention to enhance clinical skills learning in the first
      semester of nursing education. The study had an exploratory design, where
      qualitative data were collected in focus group interviews involving 18 students
      and four teachers. The participants had generally positive experiences of the
      intervention. The findings showed that organisation, time usage, an observer
      role, re-training and structured reflection enhanced systematic feedback by
      students. We conclude that an educational intervention based on theoretically
      sound learning tools and pedagogical principles improved students' skills
      acquisition and gave the teachers a common educational platform.

PMID- 29353105
TI  - Biomimetic and enzyme-responsive dynamic hydrogels for studying cell-matrix
      interactions in pancreatic ductal adenocarcinoma.
AB  - The tumor microenvironment (TME) governs all aspects of cancer progression and in
      vitro 3D cell culture platforms are increasingly developed to emulate the
      interactions between components of the stromal tissues and cancer cells. However,
      conventional cell culture platforms are inadequate in recapitulating the TME,
      which has complex compositions and dynamically changing matrix mechanics. In this
      study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system
      through integrating modular thiol-norbornene photopolymerization and enzyme
      triggered on-demand matrix stiffening. In particular, gelatin was dually modified
      with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein
      photo-crosslinkable (through thiol-norbornene gelation) and responsive to
      tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition
      to the modified gelatin that provides basic cell adhesive motifs and protease
      cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was
      modularly and covalently incorporated into the cell-laden gel network. We
      systematically characterized macromer modification, gel crosslinking, as well as
      enzyme-triggered stiffening and degradation. We also evaluated the influence of
      matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma
      (PDAC) cell fate in 3D. We found that either HA-containing matrix or a
      dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly,
      these two factors synergistically induced cell phenotypic changes that resembled
      cell migration and/or invasion in 3D. Additional mRNA expression array analyses
      revealed changes unique to the presence of HA, to a stiffened microenvironment,
      or to the combination of both. Finally, we presented immunostaining and mRNA
      expression data to demonstrate that these irregular PDAC cell phenotypes were a
      result of matrix-induced epithelial-mesenchymal transition (EMT).

PMID- 29353106
TI  - Perineurium-like sheath derived from long-term surviving mesenchymal stem cells
      confers nerve protection to the injured spinal cord.
AB  - The functional multipotency enables mesenchymal stem cells (MSCs) promising
      translational potentials in treating spinal cord injury (SCI). Yet the fate of
      MSCs grafted into the injured spinal cord has not been fully elucidated even in
      preclinical studies, rendering concerns of their safety and genuine efficacy.
      Here we used a rat spinal cord transection model to evaluate the cell fate of
      allograft bone marrow derived MSCs. With the application of immunosuppressant,
      donor cells, delivered by biocompatible scaffold, survived up to 8 weeks post
      grafting. Discernible tubes formed by MSCs were observed beginning 2 weeks after
      transplantation and they dominated the morphological features of implanted MSCs
      at 8 weeks post-grafting. The results of immunocytochemistry and transmission
      electron microscopy displayed the formation of perineurium-like sheath by donor
      cells, which, in a manner comparable to the perineurium in peripheral nerve,
      enwrapped host myelins and axons. The MSC-derived perineurium-like sheath
      secreted a group of trophic factors and permissive extracellular matrix, and
      served as a physical and chemical barrier to insulate the inner nerve fibers from
      ambient oxidative insults by the secretion of soluble antioxidant, superoxide
      dismutase-3 (SOD3). As a result, many intact regenerating axons were preserved in
      the injury/graft site following the forming of perineurium-like sheath. A
      parallel study utilizing a good manufacturing practice (GMP) grade human
      umbilical cord-derived MSCs or allogenic MSCs in an acute contusive/compressive
      SCI model exhibited a similar perineurium-like sheath formed by surviving donor
      cells in rat spinal cord at 3 weeks post-grafting. The present study for the
      first time provides an unambiguous morphological evidence of perineurium-like
      sheath formed by transplanted MSCs and a novel therapeutic mechanism of MSCs in
      treating SCI.

PMID- 29353108
TI  - Chronic Graft-versus-Host Disease: A Long Road Ahead.

PMID- 29353110
TI  - Orchestration of Chemomobilization and G-CSF Administration for Successful
      Hematopoietic Stem Cell Collection.
AB  - Successful collection of peripheral blood stem cells (PBSCs) depends on the
      optimal orchestration of mobilization chemotherapy, granulocyte colony
      stimulating factor (G-CSF) application, and CD34+ cell number assessment in the
      peripheral blood (PB). However, determining the optimal timing in accordance to
      the applied chemomobilization regimen can be challenging. Although most centers
      apply their own local timing schedules, a reliable timetable including the
      currently most often used mobilization regimens is lacking. We present a
      comprehensive analysis of the timing modalities for 11 of the most commonly used
      chemomobilization regimens. A retrospective analysis was performed on the
      clinical and PBSC collection parameters (including duration of G-CSF application,
      time point of CD34+ assessment, PB CD34+ cell count, number of leukapheresis [LP]
      sessions, processed blood volume, and CD34+ collection results) of 91
      representatively selected patients who had undergone stem cell mobilization at 2
      collection centers. Six to 10 patients were analyzed per regimen with a variety
      of diagnoses, including multiple myeloma, malignant lymphoma, and sarcoma. No
      collection failures (<2 * 106 CD34+ cells/kg body weight) were observed. All
      analyzed patients successfully reached their individual collection goal in
      adherence to the given schedule of chemotherapy, application of G-CSF,
      measurement of CD34+ cells, and subsequent LP. The presented data on the timing
      of chemomobilization, G-CSF application, and stem cell collection may be helpful
      in clinical decision making and contribute to a more transparent and predictable
      treatment process.

PMID- 29353109
TI  - Shortened-Duration Tacrolimus after Nonmyeloablative, HLA-Haploidentical Bone
      Marrow Transplantation.
AB  - With post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease
      (GVHD) prophylaxis, nonmyeloablative HLA-haploidentical (NMA haplo) and HLA
      matched blood or marrow transplantation (BMT) have comparable outcomes. Early
      discontinuation of immunosuppression may reduce the risk of relapse and improve
      immune reconstitution, but may increase the risk of GVHD. We conducted a
      prospective trial of NMA haplo BMT for patients with hematologic malignancies
      (median age, 61 years), evaluating the safety of early discontinuation of
      tacrolimus. All patients received T cell-replete bone marrow followed by high
      dose PTCy, mycophenolate mofetil, and tacrolimus. Tacrolimus was prespecified to
      stop without taper at day +90, +60, or +120, contingent on having >=5% donor T
      cells, no relapse, and no grade II-IV acute or significant chronic GVHD. Safety
      stopping rules were based on >=5% graft failure, >=10% nonrelapse mortality
      (NRM), or a >=20% combined incidence of severe acute and chronic GVHD from the
      tacrolimus stop date through day +180. Of the 47 patients in the day +90 arm, 23
      (49%) stopped tacrolimus as planned. Of the 55 patients in the day +60 arm, 38
      (69%) stopped as planned. Safety stopping criteria were not met. In both arms, at
      day +180, the probability of grade II-IV acute GVHD was <40%, that of grade III
      IV acute GVHD was <8%, and that of NRM was <5%. The 1-year probabilities of
      chronic GVHD and NRM were <15% and <10%, respectively, in both arms. The 1-year
      GVHD-free relapse-free survival was higher in the day 60 arm. Thus, stopping
      tacrolimus as early as day +60 is feasible and carries acceptable risks after NMA
      haplo BMT with PTCy. This approach may facilitate post-transplantation strategies
      for relapse reduction.

PMID- 29353111
TI  - Investigation of phase separated polyimide blend films containing boron nitride
      using FTIR imaging.
AB  - Immiscible aromatic polyimide (PI) blend films and a PI blend film incorporated
      with thermally conductive boron nitride (BN) were prepared, and their phase
      separation behaviors were examined by optical microscopy and FTIR imaging. The
      2,2'-bis(trifluoromethyl)benzidine (TFMB)-containing and 4,4'-thiodianiline (TDA)
      containing aromatic PI blend films and a PI blend/BN composite film show two
      clearly separated regions; one region is the TFMB-rich phase, and the other
      region is the TDA-rich phase. The introduction of BN induces morphological
      changes in the immiscible aromatic PI blend film without altering the composition
      of either domain. In particular, the BN is selectively incorporated into the TDA
      rich phase in this study.

PMID- 29353112
TI  - Bioleaching of metals from WEEE shredding dust.
AB  - A bioleaching process developed in two separate steps was investigated for the
      recovery of base metals, precious metals and rare earth elements from dusts
      generated by Waste Electrical and Electronic Equipment (WEEE) shredding. In the
      first step, base metals were almost completely leached from the dust in 8 days by
      Acidithiobacillus thiooxidans (DSM 9463) that lowered the pH of the leaching
      solution from 3.5 to 1.0. During this step, cerium, europium and neodymium were
      mobilized at high percentages (>99%), whereas lanthanum and yttrium reached an
      extraction yield of 80%. In the second step, the cyanide producing Pseudomonas
      putida WSC361 mobilized 48% of gold within 3 h from the A. thiooxidans leached
      shredding dust. This work demonstrated the potential application of
      biohydrometallurgy for resource recovery from WEEE shredding dust, destined to
      landfill disposal, and its effectiveness in the extraction of valuable
      substances, including elements at high supply risk as rare earths.

PMID- 29353113
TI  - Cadmium immobilization in river sediment using stabilized nanoscale zero-valent
      iron with enhanced transport by polysaccharide coating.
AB  - Proper management of metal-contaminated sediment plays a key role in sediment
      recovery and reuse. This study synthesized two kinds of stabilized nanoscale zero
      valent iron (nZVI) with starch (S-nZVI) and carboxymethyl cellulose (C-nZVI) for
      the in situ immobilization of Cd(II) in river sediment and investigated their
      transport in porous media. Experimental data showed that when the sediment sample
      was treated with C-nZVI for 56 days at a dosage ranging from 5 to 10 mg/g
      sediment as Fe0, the TCLP (toxicity characteristic leaching procedure)
      leachability of Cd(II) in the sediment decreased by 93.75-96.43%, and the PBET
      (physiologically-based extraction test) bioaccessibility of Cd(II) decreased by
      22.79-71.32%. Additionally, the acid soluble fraction of Cd(II) was partially
      transformed to a residual fraction, resulting in a 32.4-33.1% decrease of acid
      soluble Cd(II) and a 125.4-205.6% increase of the residual-Cd(II) fraction.
      Surface complexation with iron oxyhydroxide minerals might be the main mechanism
      of Cd(II) immobilization in sediment. Column experiments indicate that starch or
      carboxymethyl cellulose (CMC) could extend the travel distance of nZVI, but
      inherent site physical and chemical heterogeneities still posed challenges for
      nanoparticle transport. Over all, this study verifies the effectiveness of
      stabilized nZVI for Cd(II) immobilization in sediment and discusses the potential
      immobilization mechanism.

PMID- 29353114
TI  - Toxic hazards of ammonia release and population vulnerability assessment using
      geographical information system.
AB  - Today, chemical industries manufacture, store and transport evermore hazardous
      substances and hence the risk of accidental releases of these chemicals can
      become more and more catastrophic in the context of increasing population and
      their requirements. The damage potential is proportional to the population
      characteristics of the location as well as various meteorological factors and
      geographical features. For the risk assessment of ammonia toxicity, the storage
      facility at Eloor industrial area is taken as a sample. Pollutant dispersion
      model - Areal Locations of Hazardous Atmosphere (ALOHA) is utilized to predict
      the toxicity impacted distance of ammonia. The model estimates the vulnerable
      areas, which may be affected toxically by an Ammonia release by integrating
      information about chemical properties of the substance, weather conditions
      prevalent in the area and release conditions. Risk assessment is done for four
      different atmospheric conditions, typical to the prevailing seasons and affected
      area is estimated in each scenario. To determine the affected population, the
      areal interpolation method in GIS database is also employed in this study, which
      illustrates the toxically impacted areas and the population in need of immediate
      help and evacuation. Such studies can serve as an effective tool for decision
      makers to prepare an emergency plan in case of accidental releases.

PMID- 29353115
TI  - Efficient removal of Acid Green 25 dye from wastewater using activated Prunus
      Dulcis as biosorbent: Batch and column studies.
AB  - Biosorbent synthesized from dead leaves of Prunus Dulcis with chemical activation
      during the synthesis was applied for the removal of Acid Green 25 dye from
      wastewater. The obtained biosorbent was characterized using Brunauer-Emmett
      Teller analysis, Fourier transform-infrared spectroscopy and scanning electron
      microscopy measurements. It was demonstrated that alkali treatment during the
      synthesis significantly increased surface area of biosorbent from 67.205 to
      426.346 m2/g. The effect of various operating parameters on dye removal was
      investigated in batch operation and optimum values of parameters were established
      as pH of 2, 14 g/L as the dose of natural biosorbent and 6 g/L as the dose of
      alkali treated biosorbent. Relative error values were determined to check fitting
      of obtained data to the different kinetic and isotherm models. It was established
      that pseudo-second order kinetic model and Langmuir isotherm fitted suitably to
      the obtained batch experimental data. Maximum biosorption capacity values were
      estimated as 22.68 and 50.79 mg/g for natural biosorbent and for alkali activated
      Prunus Dulcis, respectively. Adsorption was observed as endothermic and
      activation energy of 6.22 kJ/mol confirmed physical type of adsorption. Column
      experiments were also conducted to probe the effectiveness of biosorbent for
      practical applications in continuous operation. Breakthrough parameters were
      established by studying the effect of biosorbent height, flow rate of dye
      solution and initial dye concentration on the extent of dye removal. The maximum
      biosorption capacity under optimized conditions in the column operation was
      estimated as 28.57 mg/g. Thomas and Yoon-Nelson models were found to be suitably
      fitted to obtained column data. Reusability study carried out in batch and
      continuous column operations confirmed that synthesized biosorbent can be used
      repeatedly for dye removal from wastewater.

PMID- 29353116
TI  - Scale-inhibition and flocculation dual-functionality of poly(acrylic acid)
      grafted starch.
AB  - Natural-polymer based water treatment agents have recently received much more
      attention due to their environmental friendliness, widespread availability, and
      prominent structural features. Starch-graft-poly(acrylic acid) (St-g-PAA) is a
      simple natural-polymer based material that can be obtained easily by a one-step
      graft copolymerization. When used as a water treatment agent, St-g-PAA exhibits
      both effective scale-inhibition performance and high turbidity removal
      efficiency. The scale-inhibition efficiency of St-g-PAA against calcium carbonate
      (CaCO3) is approximately 94% at the optimal dose in a static test of
      approximately 40 mg/L. Dispersion, crystal lattice distortion, and chelating
      effects all play important roles in the scale inhibition. When St-g-PAA is used
      as a coagulant aid for polyaluminum chloride (PAC) in the flocculation of a real
      hairwork wastewater, the highest reduction of the optimal PAC dose is more than
      30% while the turbidity reduction is about 97% at the same time, both floc size
      and compactness increase, and the final settling efficiency also improves
      evidently. The efficient bridging flocculation effects account for the effective
      turbidity removal. The prominent scale-inhibition and flocculation dual
      functionality of St-g-PAA is intrinsically ascribed to its distinct anionic
      linear branched-chain structure.

PMID- 29353117
TI  - Exposure keratopathy: Incidence, risk factors and impact of protocolised care on
      exposure keratopathy in critically ill adults.
AB  - PURPOSE: We aimed to determine the rate of exposure keratopathy (EK) in
      critically ill patients, identify risk factors for developing EK and ascertain
      the effectiveness of a protocol to prevent EK. MATERIALS AND METHODS: We
      undertook a two-phase prospective cohort study in a general adult ICU with first
      phase being observational and an eye care protocol was introduced in the second
      phase. Daily ophthalmic assessment was carried out along with recording of
      various risk factors. RESULTS: We studied 371 patients. In the first phase, the
      overall rate of EK was 21% but the rate in mechanically ventilated patients was
      56%; chi2 (1, N=257)=80.8, p<0.001. Adjusted odds ratios (AOR) for development of
      EK was 28.6 (8.19-43.37), 13.0 (3.16-54.38) and 1.2 (1.03-1.33) with incomplete
      eye closure, mechanical ventilation, and higher sequential organ failure
      assessment score respectively. Following the introduction of the protocol, the
      overall rate of EK reduced to 2.6% (3 cases); chi2 (1, N=371)=18.6, p<0.001.
      CONCLUSIONS: EK is common in critically ill patients and a simple protocol
      substantially reduces the incidence of EK and is easily achieved in clinical
      practice.

PMID- 29353118
TI  - Magnesium supplementation: Pharmacokinetics in cardiac surgery patients with
      normal renal function.
AB  - BACKGROUND: Intravenous magnesium is routinely administered in intensive care
      units (ICU) to treat arrhythmias after cardiothoracic surgery. There are no data
      on the pharmacokinetics of continuous magnesium infusion therapy. OBJECTIVE: To
      investigate the pharmacokinetics of continuous magnesium infusion, focusing on
      serum and urinary magnesium concentration, volume of distribution and half-life.
      METHODS: We administered a 10 mmol bolus of magnesium-sulfate followed by a
      continuous infusion of 3 mmol/h for 12 h in twenty cardiac surgery patients. We
      obtained blood and urine samples prior to magnesium administration and after one,
      six, and 12 h. RESULTS: Median magnesium levels increased from 1.09 (IQR 1.00
      1.23) mmol/L to 1.59 (1.45-1.76) mmol/L after 60 min (p < .001), followed by 1.53
      (1.48-1.71) and 1.59 (1.48-1.76) mmol/L after 6 and 12 h. Urinary magnesium
      concentration increased from 9.2 (5.0-13.9) mmol/L to 17 (13.6-21.6) mmol/L after
      60 min (p < .001). Cumulative urinary magnesium excretion was 28 mmol (60.9% of
      the dose given). The volume of distribution was 0.25 (0.22-0.30) L/kg. There were
      no episodes of severe hypermagnesemia (>=3 mmol/L). CONCLUSION: Combined bolus
      and continuous magnesium infusion therapy leads to a significant and stable
      increase in magnesium serum concentration despite increased renal excretion and
      redistribution.

PMID- 29353119
TI  - Diagnostic and predictive values of procalcitonin in bloodstream infections for
      nosocomial pneumonia.
AB  - PURPOSE: We evaluated the diagnostic accuracy of PCT to distinguish between gram
      negative (GN) and gram-positive (GP) bloodstream infections nosocomial pneumonia
      (NP) patients and compared PCT levels with the pneumonia severity index (PSI) for
      predicting mortality. METHODS: Data were collected retrospectively for blood
      culture-positive NP patients between January 2014 and August 2016. PCT levels
      were compared between patients with GN versus GP infections. Outcome variables
      included 28- and 60-day mortality. RESULTS: PCT level was higher in GN infections
      than in GP infections. PCT could differentiate between GN and GP infections with
      an AUC value of 0.706. At a PCT cutoff of 5.4 ng/mL, the specificity for GN
      infections were 80.3%. The AUCs for 28- and 60-day mortality were 0.758 and 0.759
      for PSI, and 0.620 and 0.634 for PCT. Serum PCT level was less predictive of
      mortality in GN NP patients compared with that for GP NP patients. There was a
      significantly positive correlation between PCT and PSI, and the correlation in GP
      NP patients was better than that in GN NP patients. CONCLUSIONS: PCT could
      differentiate between GN and GP bloodstream infections in patients with NP.
      However, PCT levels were less predictive of mortality compared with the PSI.

PMID- 29353120
TI  - Phase angle assessment in critically ill cancer patients: Relationship with the
      nutritional status, prognostic factors and death.
AB  - PURPOSE: To evaluate the relationship between phase angle (PA) and nutritional
      status and the prognostic significance of PA in critically ill cancer patients.
      METHODS: 31 patients that had been admitted to the intensive care unit (ICU) of a
      center on oncology were evaluated. Their PA was obtained from their bioelectrical
      impedance within 48 h of the ICU admission. The logistic regression analysis of
      Cox was used in order to identify the independent predictors of the outcomes.
      RESULTS: Negative and significant correlations were observed between the PA and
      the following variables: the length of hospital ward stay, the length of ICU
      stay, the total time of hospital stay, the mechanical ventilation time, and the
      acute physiology and chronic health evaluation II (APACHE II) scores. A positive
      correlation was ascertained between the PA and albumin. PA was significantly
      associated with death. Patients with a PA <=3.8 degrees  presented a
      significantly shorter survival time than those with a PA >3.8 degrees .
      CONCLUSION: PA was a prognostic marker in this population, independently of
      previously established prognostic factors. PA can represent a clinically feasible
      approach for the initial identification of critically ill cancer patients who
      require an early and specialized nutritional intervention.

PMID- 29353121
TI  - Tau-PET imaging with [18F]AV-1451 in primary progressive apraxia of speech.
AB  - Apraxia of speech is a motor speech disorder characterized by combinations of
      slow speaking rate, abnormal prosody, distorted sound substitutions, and trial
      and-error articulatory movements. Apraxia of speech is due to abnormal planning
      and/or programming of speech production. It is referred to as primary progressive
      apraxia of speech (PPAOS) when it is the only symptom of a neurodegenerative
      condition. Past reports suggest an association of PPAOS with primary 4-repeat
      (4R) tau (e.g., progressive supranuclear palsy, corticobasal degeneration),
      rather than amyloid, pathology. The goal of the current study was to investigate
      the distribution of tau tracer uptake using [18F]AV-1451 positron emission
      tomography (PET) imaging in patients with PPAOS. Fourteen PPAOS patients
      underwent [18F]AV-1451 PET (tau-PET) imaging, [C11] Pittsburgh Compound B (PiB)
      PET and structural MRI and were matched 3:1 by age and sex to 42 cognitively
      normal controls. Tau-PET uptake was assessed at the region-of-interest (ROI)
      level and at the voxel-level. The PPAOS group (n = 14) showed increased tau-PET
      uptake in the precentral gyrus, supplementary motor area and Broca's area
      compared to controls. To examine whether tau deposition in Broca's area was
      related to the presence of aphasia, we examined a subgroup of the PPAOS patients
      who had predominant apraxia of speech, with concomitant aphasia (PPAOSa; n = 7).
      The PPAOSa patients showed tau-PET uptake in the same regions as the whole group.
      However, the remaining seven patients who did not have aphasia showed uptake only
      in superior premotor and precentral cortices, with no uptake observed in Broca's
      area. This cross-sectional study demonstrates that elevated tau tracer uptake is
      observed using [18F]AV-1451 in PPAOS. Further, it appears that [18F]AV-1451 is
      sensitive to the regional distribution of tau deposition in different stages of
      PPAOS, given the relationship between tau signal in Broca's area and the presence
      of aphasia.

PMID- 29353122
TI  - Asparagine and sugars are both required to sustain secondary axis elongation
      after bud outgrowth in Rosa hybrida.
AB  - Nitrogen is required for optimal plant growth, especially in young organs such as
      secondary axes (axes II) after axillary bud outgrowth. Several studies have shown
      an increase of nitrogen concentration in xylem sap concomitantly with bud
      outgrowth, but the relation between nitrogen, sugars and plant hormones in axis
      II still remains unclear. We investigated in Rosa hybrida the involvement of
      nitrogen nutrition in axis II elongation in relation with sugars and cytokinins
      using 15N-labeled nitrate and sugars, amino acids and cytokinin quantifications.
      Besides, we measured the effect of the exogenous supply of these compounds on
      axis II elongation using in vitro excised bud culture. We demonstrated that
      nitrogen in the axis II comes mainly from new root uptake after decapitation.
      Asparagine, which concentration increases in sap exudates and tissues during axis
      II elongation, was the sole amino acid able to sustain an efficient elongation in
      vitro when supplied in combination with sucrose.

PMID- 29353123
TI  - A locking compression plate versus the gold-standard non-locking plate with lag
      screw for first metatarsophalangeal fusion: A biomechanical comparison.
AB  - INTRODUCTION: The treatment of end-stage first metatarso-phalangeal joint (MTP)
      arthritis has been arthrodesis. A dorsal non-locking plate with a lag screw has
      been the standard traditional fixation method. This study compares the
      biomechanical strength of a locking compression plate (LCP) with and without
      internal compression versus this known gold standard. METHODS: In group 1, six
      matched pairs of cadaver great toes were used to compare the standard non-locking
      dorsal plate and 3.5mm lag screw to an anatomic locking compression plate in
      which a lag screw was utilized rather than the internal compression features of
      the plate. In group 2, another six matched pairs of cadaver great toes were used
      to compare the gold standard to the locking compression plate, utilizing the
      plate's internal compression feature instead of a lag screw. A material testing
      system (MTS) machine applied loads to the MTP joints and measured displacement
      and stiffness of the constructs. The stiffness of the constructs (Young's
      modulus) was calculated from the force-displacement curves, and the displacement
      was measured. RESULTS: The locking compression plate group that used the
      compression features of the plate, without the lag screw, had less joint
      displacement and higher stiffness than control (p<0.05). The same plating
      construct in which a lag screw was used rather than internal compression of the
      plate was found to be stiffer than the control (p<0.05), but displacement was not
      statistically significant. DISCUSSION: The results suggest that a locking
      compression plate alone provides the stiffest construct for a first MTP joint
      fusion.

PMID- 29353124
TI  - Projecting environmental suitable areas for malaria transmission in China under
      climate change scenarios.
AB  - INTRODUCTION: The proportion of imported malaria cases in China has increased
      over recent years, and has presented challenges for the malaria elimination
      program in China. However, little is known about the geographic distribution and
      environmental suitability for malaria transmission under projected climate change
      scenarios. METHODS: Using the MaxEnt model based on malaria presence-only
      records, we produced environmental suitability maps and examined the relative
      contribution of topographic, demographic, and environmental risk factors for P.
      vivax and P. falciparum malaria in China. RESULTS: The MaxEnt model estimated
      that environmental suitability areas (ESAs) for malaria cover the central, south,
      southwest, east and northern regions, with a slightly wider range of ESAs
      extending to the northeast region for P. falciparum. There was spatial agreement
      between the location of imported cases and area environmentally suitable for
      malaria transmission. The ESAs of P. vivax and P. falciparum are projected to
      increase in some parts of southwest, south, central, north and northeast regions
      in the 2030s, 2050s, and 2080s, by a greater amount for P. falciparum under the
      RCP8.5 scenario. Temperature and NDVI values were the most influential in
      defining the ESAs for P. vivax, and temperature and precipitation the most
      influential for P. falciparum malaria. CONCLUSION: This study estimated that the
      ESA for malaria transmission in China will increase with climate change and
      highlights the potential establishment of further local transmission. This model
      should be used to support malaria control by targeting areas where interventions
      on malaria transmission need to be enhanced.

PMID- 29353126
TI  - Evaluation of gamma contribution in a neutron calibration field of Am-Be241
      source.
AB  - The paper presents the evaluation of gamma contribution in a neutron calibration
      field of a 241Am-Be source. The characterization of gamma flux spectra and gamma
      ambient dose equivalent rates has been performed using a portable NaI(Tl) gamma
      spectrometer. For obtaining the gamma ambient dose equivalent rates from the
      measured spectra, two approaches were applied based on the applications of the
      G(E) function and the ICRP 74 conversion factors, respectively. Comparison of the
      gamma ambient dose equivalent rates obtained from the two approaches shows an
      agreement within 5%. The gamma contribution in the neutron calibration field is
      evaluated about 2.3-3.3% of the total neutron ambient dose equivalent rate in the
      distance range of 100-250cm.

PMID- 29353125
TI  - Relationship between serum trimethylamine N-oxide and exposure to dioxin-like
      pollutants.
AB  - Trimethylamine N-oxide (TMAO) is a diet and gut microbiota-derived metabolite
      that has been linked to cardiovascular disease risk in human studies and animal
      models. TMAO levels show wide inter and intra individual variability in humans
      that can likely be accounted for by multiple factors including diet, the gut
      microbiota, levels of the TMAO generating liver enzyme Flavin-containing
      monooxygenase 3 (FMO3) and kidney function. We recently found that dioxin-like
      (DL) environmental pollutants increased FMO3 expression to elevate circulating
      diet-derived TMAO in mice, suggesting that exposure to this class of pollutants
      might also contribute to inter-individual variability in circulating TMAO levels
      in humans. To begin to explore this possibility we examined the relationship
      between body burden of DL pollutants (reported by serum lipid concentrations) and
      serum TMAO levels (n = 340) in the Anniston, AL cohort, which was highly exposed
      to polychlorinated biphenyls (PCBs). TMAO concentrations in archived serum
      samples from the Anniston Community Health Survey (ACHS-II) were measured, and
      associations of TMAO with 28 indices of pollutant body burden, including total
      dioxins toxic equivalent (TEQ), were quantified. Twenty-three (22 after
      adjustment for multiple comparisons) of the 28 indices were significantly
      positively associated with TMAO. Although the design of ACHS-II does not enable
      quantitative assessment of the contributions of previously known determinants of
      TMAO variability to this relationship, limited multivariate modeling revealed
      that total dioxins TEQ was significantly associated with TMAO among females
      (except at high BMIs) but not among males. Our results from this cross-sectional
      study indicate that exposure to DL pollutants may contribute to elevated serum
      TMAO levels. Prospective longitudinal studies will be required to assess the
      joint relationship between DL pollutant exposures, other determinants of TMAO,
      and health outcomes.

PMID- 29353127
TI  - Physical comorbidities increase the risk of psychiatric comorbidity in immune
      mediated inflammatory disease.
AB  - OBJECTIVE: We tested the association between physical comorbidity and incident
      depression, anxiety disorder and bipolar disorder in three immune-mediated
      inflammatory diseases (IMID): inflammatory bowel disease (IBD), multiple
      sclerosis (MS) and rheumatoid arthritis (RA) versus age-, sex- and geographically
      matched controls. METHODS: Using population-based administrative data we
      identified 6119 persons with IBD, 3514 persons with MS, 10,206 persons with RA
      and 97,727 matched controls. We identified incident cases of depression, anxiety
      disorder and bipolar disorder in these populations. We evaluated the association
      of physical comorbidities with incident psychiatric comorbidity using Cox
      regression, adjusting for sociodemographic factors and index year. RESULTS: The
      risk of incident depression, anxiety disorders and bipolar disorder was higher in
      each IMID cohort versus their matched cohorts. The risk of incident psychiatric
      comorbidity increased with an increasing number of physical comorbidities for
      each psychiatric comorbidity evaluated, across all IMID. Adjustment for physical
      comorbidity did not attenuate the increased risk of psychiatric comorbidity in
      the IMID cohorts versus their matched cohorts. CONCLUSION: The increased
      incidence of psychiatric comorbidity in IMID versus matched general population
      cohorts is not accounted for by their increased prevalence of physical
      comorbidities. However, within IMID cohorts, physical comorbidity increases the
      risk of psychiatric comorbidity.

PMID- 29353129
TI  - Keeping it together and falling apart: Women's dynamic experience of birth.
AB  - OBJECTIVE: To explore the complexity of women's birth experiences in the context
      in which they occur and to describe how these influence women's well-being in
      labor. DESIGN: Qualitative method with a phenomenological approach, following the
      analysis principles of van Manen. PARTICIPANTS AND SETTING: Eight women from
      different ethnic and socioeconomic backgrounds in Atlanta, Georgia, United States
      with a recent, healthy birth were interviewed twice about their experience of the
      labor journey. The first interview was 3-12 weeks post-partum, with the second
      interview at 10-22 weeks post-partum. FINDINGS: The phenomenon of childbirth was
      a dynamic fluctuating between keeping it together and falling apart. The changes
      in emotion were created by a sensitive feedback loop between the woman and her
      environment, the physical space, and interactions with humans present. Four
      characteristics supported and created this phenomenon: confidence, comfort,
      agency and connection. Confidence was believing in one's physical ability to
      birth the baby while at the same time, having the emotional resources to cope
      with the experience. Comfort was essential to manage pain and difficult emotions.
      The presence of comfort changed the meaning and experience of pain and increased
      relaxation. Agency was overtly supported in labor, but compromised by hospital
      routine and unresponsive caregiver practices, and was diminished by women's
      vulnerability in labor. When agency was compromised, falling apart increased, and
      there was a move towards intense negative emotion. In labor, women wanted an
      authentic human connection, being known as a person. This connection was a
      mechanism to support the other characteristics of comfort, confidence, and
      agency. IMPLICATIONS FOR PRACTICE: Clinicians need to accommodate the complex,
      dynamic fluctuations of emotion during birth addressing both the physical and non
      physical aspects of the person. Birth care practices and childbirth research need
      to account for the complexity of birth as a holistic experience, specifically
      regarding the emotional shifts as well as the women's sensitivity to the
      environment and everything contained in it. There is a need for more research
      related to the dynamics of emotional changes in labor, how these changes affect
      labor physiology and influence normal birth and birth outcomes.

PMID- 29353128
TI  - Adoption, penetration, and effectiveness of a secondary risk screener for
      intimate partner violence: Evidence to inform screening practices in integrated
      care settings.
AB  - OBJECTIVE: Veterans Health Administration (VHA) has implemented screening for
      past-year intimate partner violence (IPV) in some healthcare facilities along
      with secondary screening of risk for severe violence among those screening
      positive in order to facilitate follow-up care for high-risk patients. We
      evaluated the adoption, penetration, and effectiveness of secondary screening as
      a tool to facilitate timely follow-up services. METHODS: Retrospective review of
      medical records (screening and healthcare use) of 774 women screening positive
      for past-year IPV (IPV+) at 11 facilities nationwide from April 2014-April 2016.
      Chi-square and t-tests examined factors related to secondary screening. RESULTS:
      Three of eleven (27.3%) facilities that implemented primary IPV screening adopted
      secondary screening. At adopting sites, 56.4% eligible (i.e., IPV+) women
      received secondary screening. Among 185 IPV+ women who completed secondary
      screening, 33.0% screened positive for severe IPV. Screening positive during
      secondary screening was associated with higher rate of psychosocial care within
      60 days (73.8% vs. 54.0% of IPV+ patients screening negative; p < .05),
      posttraumatic stress disorder diagnosis (31.1% vs. 15.3%; p < .05), and being
      physically threatened or harmed (>50% vs. <15%; p < .001). CONCLUSIONS: Secondary
      risk assessment following IPV screening may expedite access to psychosocial
      follow-up care in integrated healthcare settings. However, program uptake needs
      to be enhanced.

PMID- 29353130
TI  - Serum miR-1181 and miR-4314 associated with ovarian cancer: MiRNA microarray data
      analysis for a pilot study.
AB  - OBJECTIVE: This study aims to identify serum microRNAs (miRNAs) related to
      ovarian cancer. STUDY DESIGN: MiRNA profiling data (GSE79943) were generated from
      the Gene Expression Omnibus, including 3 serum samples from healthy individuals
      and 4/3/16/6 serum samples from patients with ovarian cancer stage I/II/III/IV.
      Differentially expressed miRNAs (DEmiRNAs) were identified between controls and
      ovarian cancer stage I/II/III/IV by using limma package (p-value <0.05 and |log2
      fold change| >=0.5). miRWALK2.0 database was used to find experiment-validated
      targets of DEmiRNAs, and CTD database was utilized to screen known genes related
      to ovarian cancer. clusterProfiler package was used to perform pathway enrichment
      analysis of DEmiRNAs. Targets of DEmiRNAs were validated by using GSE40595,
      involving 8 normal ovarian stroma, 31 ovarian cancer stroma, 6 human ovarian
      surface epthelium, and 32 ovarian tumor epthelial component. RESULTS: Between
      stage I/II/III/IV and control, 39/143/29/39 DEmiRNAs were identified, which were
      regarded as key miRNAs. Between 4 DEmiRNA sets, 15 common DEmiRNAs were
      identified (e.g. up-regulated hsa-miR-1181 and hsa-miR-4314). Hsa-miR-1181
      participated in "Jak-STAT signaling pathway" and "miRNAs in cancer"; hsa-miR-4314
      took part in cancer-related pathways. STAT3 and KRAS, known marker genes of
      ovarian cancer, were targeted by hsa-miR-1181 and hsa-miR-4314, respectively.
      Besides, FOXP1 was targeted by hsa-miR-1181; FOXP1-AS1 and FOXP1-IT1 were down
      regulated in ovarian cancer. GRWD1, IP6K1, and NEGR1 were targeted by hsa-miR
      4314; GRWD1, IP6K1, and NEGR1 were down-regulated in ovarian tumor. CONCLUSION:
      MiR-1181 and miR-4314 might promote ovarian tumorigenesis via down-regulating
      FOXP1 and GRWD1/IP6K1/NEGR1, respectively. In addition, the 15 common DEmiRNAs
      might provide directions for ovarian cancer diagnosis.

PMID- 29353131
TI  - Dermatoglyphic patterns on fingers and gynecological cancers.
AB  - OBJECTIVES: Fingerprints have so far been used for determining the basis of
      certain malignant diseases, with positive outcomes. Considering the high rates of
      cancer-related mortality in Iran, this study was conducted for the purpose of
      examining the dermatoglyphic pattern of fingers in patients with gynecological
      cancers as compared to healthy people. STUDY DESIGN: The present study was
      conducted on 151 women with gynecological cancers as the case group and 152
      healthy women with no history of such cancers as control group. The dematographic
      details of participants from both control and case groups were collected using a
      checklist, and the pattern of their fingerprints was prepared and examined. The
      data were analyzed for their significance using chi-square test and t- test. Odds
      ratio with 95% confidence intervals were calculated. RESULTS: Dermatoglyphic
      analysis showed that arch and loop patterns significantly changed in cases group
      as compared to control. However, the odds ratio suggested that loop pattern in 6
      or more fingers might be a risk factor for developing gynecological cancers.
      CONCLUSION: Our results showed that there is an association between fingerprint
      patterns and gynecological cancers and so, dermatoglyphic analysis may aid in the
      early diagnosis of these cancers.

PMID- 29353132
TI  - Supporting parents through stillbirth: A qualitative study exploring the views of
      health professionals and health care staff in three hospitals in England.
AB  - OBJECTIVE: To investigate the views of a range of hospital based health
      professionals and health care staff involved in the management of stillbirth.
      STUDY DESIGN: A qualitative pilot study informed by grounded theory conducted in
      three hospital trusts in the North East of England. In total, 21 consultant
      obstetricians, 3 trainees (including 1 senior trainee), 29 midwives, 3 midwife
      sonographers and 4 chaplains took part in six focus groups and two semi
      structured interviews. RESULTS: Two different approaches in stillbirth management
      could be detected in our study. One approach emphasised the existing evidence
      base and patient directed choice whilst the other emphasised tradition and
      profession-directed care. These differences were particularly apparent in choices
      over mode of delivery, and the location of women as well as the time interval
      between diagnosis of an IUD and delivery. The existence of these two approaches
      was underscored by a lack of high quality evidence. CONCLUSION: Robust, high
      quality evidence is needed regarding the longer term psychological and emotional
      sequelae of different modes of delivery and varying time intervals and locations
      of women between diagnosis and delivery in stillbirth. If the competing
      discourses demonstrated here are found elsewhere then such need to be considered
      in any future policy development, evidence implementation and training
      programmes.

PMID- 29353133
TI  - Maternal serum uric acid levels and blood pressure during pregnancy: A community
      based cohort study.
AB  - OBJECTIVE: Studies find both very low and high serum uric acid (UA) levels are
      related to oxidative stress and to conditions such as cardiovascular diseases and
      chronic kidney disease in the general population. Pregnancy studies have focused
      only on high maternal UA. In present study, we tested whether unusually high and
      low levels of maternal serum UA are associated with increases in blood pressure
      (BP) during pregnancy. STUDY DESIGN: The Pregnancy Outcomes and Community Health
      Study enrolled 3019 pregnant women between their 16th-27th week of pregnancy from
      52 clinics in 5 Michigan communities (1998-2004). UA levels were measured in
      maternal blood collected at enrollment from a sub-cohort of 1223 participants. BP
      was abstracted from prenatal medical records; these analyses used highest
      recorded diastolic BP (DBP) and its companion systolic BP (SBP). Mean arterial
      pressure (MAP) was calculated using the formula of (2 * DBP + SBP)/3. Covariates,
      including maternal race/ethnicity, age at enrollment, education level, medical
      insurance status, body mass index before pregnancy, parity, smoking during
      pregnancy, alcohol use during pregnancy, and gestational week at blood
      collection, were considered as potential confounding variables. Associations
      between UA levels and BP were evaluated with linear spline or multiple linear
      regression models. Models' robustness was examined with bootstrap estimation of
      variance, sensitivity analysis, and 10-fold cross-validation. RESULTS: Both DBP
      and MAP had a J-shaped relationship with maternal UA; the breakpoints (nadirs)
      were 0.153 and 0.161 mmol/L UA, respectively. For DBP versus UA, adjusted
      regression coefficient (beta) = -95.67 (standard error (SE) = 37.67 and p = 0.01)
      for the left and adjusted beta = 48.95 (SE = 9.56 and p < 0.01) for the right;
      for MAP versus UA, adjusted beta = -58.48 (SE = 31.42 and p = 0.06) for the left
      and adjusted beta = 52.23 (SE = 11.39 and p < 0.01) for the right. Maternal SBP
      followed a positive linear trend with UA levels (adjusted beta = 37.75, SE =
      12.93, and p < 0.01). All results were robust. CONCLUSION: Extreme high and low
      maternal serum UA levels may be informative in studying maternal blood pressure
      during pregnancy.

PMID- 29353134
TI  - Knowledge, attitudes and practices of pregnant women in Martinique in the
      immediate aftermath of the Zika virus outbreak.
AB  - INTRODUCTION: The WHO and the HCSP recognize the Zika virus as a public health
      problem of international concern primarily because of the foetal risks. During
      the epidemic in Martinique, several modifications to the normal obstetrical
      follow-up were set up and information had to be delivered to pregnant women about
      these modifications, the attitudes to prevent infection and the signs motivating
      additional visits. The objective of our work was to evaluate the knowledge,
      attitudes and practices of pregnant women in Martinique about the risks
      associated with Zika infection during pregnancy in the immediate aftermath of the
      epidemic. MATERIALS AND METHODS: A descriptive cross-sectional survey was
      conducted from February to May 2017. It took place through an anonymous and
      standardized face-to-face questionnaire. The questions dealt with the pregnant
      women general knowledge about the virus, information disseminated by media on
      this subject, the potential risks, the protective measures taken and the
      monitoring throughout the pregnancy in case of infection. RESULTS: The total
      sample consisted of 297 pregnant women. Despite a weak adherence to individual
      and domestic protection recommendations, we found a good level of knowledge about
      Zika virus from pregnant women in Martinique. The fetal risk in case of maternal
      infection was known for 96.6% of those surveyed, individual protective measures
      were followed by 64.6% of women, 77.0% knew where to go in case of suspected
      infection, and 79.4% reported that the modifications in follow-up mainly
      concerned ultrasound monitoring. CONCLUSION: The awareness campaign on zika virus
      had a significant impact on population's knowledge and main practical information
      was correctly captured. The information did not spill excessive fear.
      Nevertheless, modification of individual behavior appeared harder to obtain.

PMID- 29353135
TI  - Copper induces expression and methylation changes of early development genes in
      Crassostrea gigas embryos.
AB  - Copper contamination is widespread along coastal areas and exerts adverse effects
      on marine organisms such as mollusks. In the Pacific oyster, copper induces
      severe developmental abnormalities during early life stages; however, the
      underlying molecular mechanisms are largely unknown. This study aims to better
      understand whether the embryotoxic effects of copper in Crassostrea gigas could
      be mediated by alterations in gene expression, and the putative role of DNA
      methylation, which is known to contribute to gene regulation in early embryo
      development. For that purpose, oyster embryos were exposed to 4 nominal copper
      concentrations (0.1, 1, 10 and 20 MUg L-1 Cu2+) during early development assays.
      Embryotoxicity was monitored through the oyster embryo-larval bioassay at the D
      larva stage 24 h post fertilization (hpf) and genotoxicity at gastrulation 7 hpf.
      In parallel, the relative expression of 15 genes encoding putative homeotic,
      biomineralization and DNA methylation proteins was measured at three
      developmental stages (3 hpf morula stage, 7 hpf gastrula stage, 24 hpf D-larvae
      stage) using RT-qPCR. Global DNA content in methylcytosine and
      hydroxymethylcytosine were measured by HPLC and gene-specific DNA methylation
      levels were monitored using MeDIP-qPCR. A significant increase in larval
      abnormalities was observed from copper concentrations of 10 MUg L-1, while
      significant genotoxic effects were detected at 1 MUg L-1 and above. All the
      selected genes presented a stage-dependent expression pattern, which was impaired
      for some homeobox and DNA methylation genes (Notochord, HOXA1, HOX2, Lox5, DNMT3b
      and CXXC-1) after copper exposure. While global DNA methylation (5
      methylcytosine) at gastrula stage didn't show significant changes between
      experimental conditions, 5-hydroxymethylcytosine, its degradation product,
      decreased upon copper treatment. The DNA methylation of exons and the transcript
      levels were correlated in control samples for HOXA1 but such a correlation was
      diminished following copper exposure. The methylation level of some specific gene
      regions (HoxA1, Hox2, Engrailed2 and Notochord) displayed changes upon copper
      exposure. Such changes were gene and exon-specific and no obvious global trends
      could be identified. Our study suggests that the embryotoxic effects of copper in
      oysters could involve homeotic gene expression impairment possibly by changing
      DNA methylation levels.

PMID- 29353136
TI  - Mutual inhibition of lateral inhibition: a network motif for an elementary
      computation in the brain.
AB  - A series of classical studies in non-human primates has revealed the neuronal
      activity patterns underlying decision-making. However, the circuit mechanisms for
      such patterns remain largely unknown. Recent detailed circuit analyses in simpler
      neural systems have started to reveal the connectivity patterns underlying
      analogous processes. Here we review a few of these systems that share a
      particular connectivity pattern, namely mutual inhibition of lateral inhibition.
      Close examination of these systems suggests that this recurring connectivity
      pattern ('network motif') is a building block to enforce particular dynamics,
      which can be used not only for simple behavioral choice but also for more complex
      choices and other brain functions. Thus, a network motif provides an elementary
      computation that is not specific to a particular brain function and serves as an
      elementary building block in the brain.

PMID- 29353137
TI  - Assessment of the cytotoxicity of ionic liquids on Spodoptera frugiperda 9 (Sf-9)
      cell lines via in vitro assays.
AB  - Cytotoxicity studies are important tools for the assessment of the toxicity of
      ionic liquids (ILs). In the present study, the cytotoxicity of eleven ILs against
      Spodoptera frugiperda 9 (Sf-9) cell lines were evaluated via 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. The effect on
      cellular morphology, ultrastructural morphology, and nuclear morphology induced
      by 1-ethyl-3-methylimidazolium bromide ([C2mim][Br]) was studied via inverted
      light microscopy observation, acridine orange staining, and transmission electron
      microscope (TEM) analysis, respectively. The effect on cell DNA fragmentation,
      cell apoptosis and cell cycle induced by [C2mim][Br] was also investigated via
      DNA agarose gel electrophoresis and flow cytometry analysis, respectively. The
      results showed that the cytotoxic effect of ILs on Sf-9 cells was related to the
      IL structures, concentrations, and length of exposure. The morphological features
      of apoptosis induced by [C2mim][Br] such as cell shrinkage and convolution,
      apoptotic bodies, pyknosis, and karyorrhesis were observed. All these phenomena
      confirmed that Sf-9 cells exposed to [C2mim][Br] died via apoptosis. This study
      complements the current knowledge about the cytotoxic properties of ILs on insect
      cells and highlights the mechanism by which ILs kill these cells. Furthermore, it
      provides a basis for further studies on the future applications of ILs as
      insecticides.

PMID- 29353138
TI  - Competitive swimmers with hypermobility have strength and fatigue deficits in
      shoulder medial rotation.
AB  - Generalised Joint Hypermobility including shoulder hypermobility (GJHS) in
      swimmers is considered an intrinsic risk factor for shoulder injuries. The aim
      was to investigate the association of GJHS with shoulder strength, fatigue
      development and muscle activity during swimming-related shoulder rotations.
      Totally, 38 competitive swimmers (aged 13-17 years) participated, 19 were
      competitive swimmers with GJHS and 19 were age, sex and club matched swimmers
      without GJHS. Concentric isokinetic force in medial and lateral rotations were
      measured at 60 degrees /s (5 repetitions) and 180 degrees /s (10 repetitions).
      Electromyographic activity was measured from upper trapezius, lower trapezius,
      serratus anterior, infraspinatus and pectoralis major muscles. Swimmers with GJHS
      produced significantly lower peak torque (0.53 vs. 0.60 Nm/kg; p = .047) and
      maximum work (0.62 vs. 0.71 J/kg; p = .031) than controls during medial rotation
      (60 degrees /s). Swimmers with GJHS showed significantly larger isokinetic
      fatigue at 180 degrees /s (0.321 J/repetition; p = .010), and tendencies to lower
      levels of muscle activity in infraspinatus (20%, p = .066) and pectoralis major
      (34%, p = .092) at 60 degrees /s during medial rotation. Young competitive
      swimmers with GJHS, despite no formal diagnosis, displayed strength and fatigue
      deficits in medial rotation, potentially inherent with greater risk of shoulder
      injury. Whether GJHS swimmers benefit from medial rotation strengthening is an
      important topic for future studies.

PMID- 29353139
TI  - Effects of lighting illuminance levels on stair negotiation performance in
      individuals with visual impairment.
AB  - BACKGROUND: Stair-related falls of older people cause a substantial financial and
      social burden. Deterioration of the visual system amongst other factors put older
      people at a high risk of falling. Improved lighting is often recommended. The aim
      of this study was to investigate the effect of lighting illuminance on stair
      negotiation performance in older individuals with visual impairment. METHODS:
      Eleven participants aged 60 or over with a vision of 6/18 or worse ascended and
      descended a staircase under: 50 lx, 100 lx, 200 lx, 300 lx and distributed 200 lx
      lighting. A motion capture system was used to measure movements of the lower
      limb. Clearance, clearance variability, temporal and spatial parameters and
      joint/segment kinematics were computed. FINDINGS: There was no effect on
      clearance or clearance variability. Participants had lower speed, cadence,
      increased cycle time and stance time in the 50 lx compared to 300 lx and
      distributed 200 lx lighting in descent. The minimum hip angle in ascent was
      increased in the 200 lx lighting. Clearance was found to be moderately correlated
      with balance scores. INTERPRETATION: Individuals with visual impairment adopt
      precautionary gait in dim lighting conditions. This does not always result in
      improvements in the parameters associated with risk of falling (e.g. clearance).

PMID- 29353140
TI  - Development of sea bream (Sparus aurata) semen vitrification protocols.
AB  - The long-term goal of this research project is to set up efficient protocol that
      can be used to develop a standardized approach for vitrification of marine fish
      spermatozoa. In particular, the aim of the present study was to develop a
      vitrification protocol for sea bream (Sparus aurata) spermatozoa. To draw up the
      protocol, we tested two different dilution media (1% NaCl and Mounib medium),
      three different vitrification devices (loops, drops and cut straws), different
      cryoprotectants (CPs) and three different equilibration times (30, 60 and 120 s).
      The effect of the different vitrification procedures on spermatozoa quality was
      checked by measuring spermatozoa motility rate and viability, mitochondrial
      membrane potential and the fertilizing ability of both fresh and post-thawed
      gametes. The best result was obtained by dropping directly into liquid nitrogen
      20 MUl of spermatozoa suspension (drop-wise method) diluted with Mounib buffer
      containing 10% Me2SO + 10% glycerol. The addition of a mixture of anti-freezing
      proteins, AFPI and AFPIII, to Mounib buffer significantly increases the
      spermatozoa quality following vitrification so confirming the usefulness of AFPs
      in improving the quality of gametes subjected to the vitrification process. The
      present study proves that vitrification offers an alternative to conventional
      sperm cryopreservation also in this species.

PMID- 29353141
TI  - Vitrification of testicular tissue from prepubertal cats in cryotubes using
      different cryoprotectant associations.
AB  - Protocols for the cryopreservation of testicular tissue are not yet established.
      In cats, few studies have been conducted on testicular vitrification using
      different cryoprotectant associations (CPAs). Thus, the objective of this study
      was to compare the effect of different CPAs on the vitrification of testicular
      tissue from prepubertal cats in cryotubes. We used 10 pairs of testicles, with
      each pair divided into 8 fragments that were distributed into different
      experimental groups. Two of these fragments were allocated into the control group
      (CG) and the other six were distributed according to the CPAs to be tested
      (dimethyl sulfoxide (DMSO)/glycerol (GLY), ethylene glycol (EG)/GLY, or DMSO/EG).
      The cryoprotectants were used at a final concentration of 5.6 M. The fragments
      were subjected to vitrification in cryotubes and after 1 week, they were warmed
      and processed for histomorphologic assessment, quantification of nucleolar
      organizer regions (NORs), and determination of cell viability. The DMSO/EG and
      EG/GLY groups presented the greatest cell separation from the cell basement
      membrane and the highest degrees of retraction of the basal membrane. In these
      aspects, DMSO/GLY did not differ from the CG and both were significantly superior
      to the other groups. In terms of cell distinction, visibility of the nucleus, and
      nuclear condensation, all the vitrified groups had significantly lower values
      than the CG, while the DMSO/GLY and EG/GLY groups did not differ between
      themselves. Through the quantification of NORs, the potential for cell
      proliferation of the CG was found to have a mean of 3.80, while DMSO/GLY
      presented a mean of 3.60, and thus there was no significant difference between
      these two groups. The proliferation potentials of both groups were significantly
      superior to that of the DMSO/EG (mean: 2.07) and EG/GLY (mean: 1.98) groups. In
      the CG and DMSO/GLY group, 91.8% and 64.2% of cells, respectively, were found to
      be viable. The cell viabilities of both groups were significantly superior to
      those of DMSO/EG (52.5%) and EG/GLY (57.10%). Vitrification in cryotubes combined
      with the use of the DMSO/GLY association was effective in maintaining the
      histomorphology, cell proliferation potential, and cell viability of testicular
      tissue from prepubertal cats after cryopreservation.

PMID- 29353142
TI  - miRNA-185 regulates the VEGFA signaling pathway in dairy cows with retained fetal
      membranes.
AB  - Retention of fetal membranes (RFM) of cows is an important reproductive
      disturbance, and is related to miRNAs. Vascular endothelial growth factor
      (VEGF)A, regulated by miRNA-185, can activate arachidonic acid (ARA) release via
      the VEGFA signaling pathway, which influences RFM. The aim of this study was to
      explore the pathogenic mechanism of RFM by investigating the regulatory
      relationship between miRNA-185 and the VEGFA signaling pathway. Serum samples of
      healthy Holstein dairy cows (n = 20) and RFM cows (n = 12), with a similar age,
      parity, weight, and milk yield, were collected to detect VEGFA and ARA
      concentrations at 6, 12, and 24 h after calving. Caruncle tissues were collected
      from healthy (n = 6) and RFM cows (n = 6) at 12 h after calving. Quantitative
      polymerase chain reaction (qPCR) and western blotting (WB) were performed to
      detect the mRNA and proteins levels, respectively, of genes involved in the VEGFA
      signaling pathway. Uterine caruncle epithelial (UCE) cells were cultured by the
      explant culture method, further purified, and subsequently treated with miRNA-185
      mimics, miRNA-185 mimics + MEK inhibitor, or left untreated as a control for
      detection of the mRNA and protein levels of genes involved in the VEGFA signaling
      pathway. The cellular supernatant was collected for measurement of ARA levels at
      12, 24 and 48 h after treatment. Serum levels of VEGFA and ARA from RFM cows were
      abnormally increased at 12 h after calving, as compared to those in healthy dairy
      cows. Expression levels of most of the investigated genes (VEGFA, PLC, PRK, RAF,
      MEK, MAPK, and PLA) were down-regulated in the caruncle tissue of RFM cows.
      However, P-p44/42 MAPK was up-regulated in the caruncle tissues of cows with RFM
      (p < .01). In UCE cells treated with the miRNA-185 mimics, expression of VEGFA,
      PLC, RAF, MEK, MAPK and PLA was significantly down-regulated, while that of P
      p44/42 MAPK was significantly up-regulated. Expression of genes involved in the
      VEGFA signaling pathway was similar to that in the in vivo assay. In UCE cells
      treated with the miRNA-185 mimics + MEK inhibitors, expression of VEGFA, PLC,
      RAF, MEK, MAPK and P-p44/42 MAPK was significantly down-regulated, while that of
      PLA was significantly up-regulated. Meanwhile, the release of ARA was increased
      (p < .01). These results demonstrate that miRNA-185 can regulate the VEGFA
      signaling pathway, especially via abnormal expression of P-p44/42 MAPK, which
      influences the release of the fetal placenta after calving.

PMID- 29353143
TI  - Contractile effect of rifaximin on bovine uterus in the presence of steroid
      hormone antagonists.
AB  - This in vitro study investigated the modulatory effect of rifaximin on bovine
      uterus contractility, in both phases of the oestrous cycle, with and without the
      steroid hormones that are predominant in the respective phases: oestrogen in the
      follicular phase and progesterone in the luteal phase. The procedures were
      conducted in an isolated organ bath by using rifaximin alone (10-4 M) and in
      association with the steroid hormone antagonists (10-5 M) tamoxifen (oestrogen
      antagonist) in the follicular phase and mifepristone (progesterone antagonist) in
      the luteal phase. The results indicated that rifaximin can stimulate uterine
      contractility. Indeed, the administration of rifaximin in the presence of
      tamoxifen or mifepristone increased the tonic activity of the uterus in both
      phases of the cycle. This result is clinically significant because rifaximin
      might also enable, in vivo, a simultaneous increase in uterine cleaning and the
      antimicrobial action against bacteria during the first 14 days postpartum, during
      the development of acute metritis.

PMID- 29353144
TI  - Effects of the HDAC inhibitor scriptaid on the in vitro development of bovine
      embryos and on imprinting gene expression levels.
AB  - This study examines the effects of the histone deacetylation inhibitor scriptaid
      (SCR) on preimplantation embryo development in vitro and on imprinting gene
      expression. We hypothesized that SCR would increase histone acetylation levels,
      enhance embryonic genome activation, and regulate imprinting and X-chromosome
      inactivation (XCI) in in vitro produced bovine embryos. Zygotes were cultured in
      vitro in presence or absence of SCR added at different time points. We assessed
      cleavage and blastocyst rates as well as the quality of blastocysts through: (i)
      differential cell counts; (ii) survival after vitrification/thawing and (iii)
      gene expression analysis -including imprinted genes. Blastocyst yields were not
      different in the control and experimental groups. While no significant
      differences were observed between groups in total cell or trophectoderm cell
      numbers, SCR treatment reduced the number of inner cell mass cells and improved
      the survival of vitrified embryos. Further, genes involved in the mechanism of
      paternal imprinting (GRB10, GNAS, XIST) were downregulated in presence of SCR
      compared with controls. These observations suggest SCR prevents deacetylation of
      paternally imprinting control regions and/or their up-regulation, as these events
      took place in controls. Whether or not such reductions in XIST and imprinting
      gene expression are beneficial for post implantation development remains to be
      clarified.

PMID- 29353145
TI  - Extremely low-frequency electromagnetic field (EMF) generates alterations in the
      synthesis and secretion of oestradiol-17beta (E2) in uterine tissues: An in vitro
      study.
AB  - An electromagnetic field (EMF) of extremely low frequency may affect
      physiological processes in mammals. The aim of the present study was to determine
      the effect of an EMF on the synthesis and secretion of oestradiol-17beta (E2) in
      the porcine uterus. Endometrial and myometrial slices were harvested on days 12
      13 of the oestrous cycle and exposed in vitro to an EMF (50 and 120 Hz, 8 mT) for
      2 and 4 h in the presence or absence of progesterone (P4). Subsequently, the
      incubation media were used to determine the concentration of E2 with RIA. Tissues
      fragments were used to study the expression of CYP19A3 mRNA using Real-Time PCR
      and the abundance of P450 aromatase using Western Blotting. The 50-Hz EMF
      increased E2 release from the endometrium and the myometrium at both time points
      of in vitro incubation. A 120-Hz EMF decreased the endometrial secretion of E2
      after 2 h of incubation and did not affect E2 secretion after 4 h. In the
      myometrium, the 120-Hz EMF increased E2 secretion after 4 h of incubation. In P4
      treated uterine fragments, no significant EMF exposition-related changes were
      observed. Only myometrial fragments incubated in the presence of P4 at 120-Hz EMF
      (4 h) released higher amounts of E2 due to EMF treatment. The 50-Hz EMF exposure
      did not change the CYP19A3 mRNA expression in endometrial fragments incubated in
      the presence or absence of P4. In myometrial fragments, the highest CYP19A3 mRNA
      expression was observed in fragments not exposed to the 50-Hz EMF and P4-treated
      tissues compared to that in fragments exposed to 50 Hz EMF and incubated with or
      without P4 and control (no EMF and no P4) fragments. The EMF at 120 Hz decreased
      basal endometrial CYP19A3 mRNA expression and did not change the expression in
      the P4-treated endometrium. In the myometrium, the EMF at 120 Hz increased
      CYP19A3 mRNA expression in slices incubated without P4 and had no effect in the
      presence of P4. The EMF exposure (50 and 120 Hz) did not affect P450 aromatase
      abundance in either the endometrium or the myometrium. In conclusion, the EMF
      induces changes in the synthesis and release of E2 in uterine tissues harvested
      during days 12-13 of the oestrous cycle. These changes are related to the EMF
      frequency used, the time of the exposition and the presence of P4. We suspect
      that this observed phenomenon might lead to changes in the intrauterine milieu of
      oestrogen, which is crucial for the proper activity of uterine tissues during the
      mid-luteal phase of the oestrous cycle.

PMID- 29353146
TI  - Case study as a means of evaluating the impact of early years leaders: Steps,
      paths and routes.
AB  - The paper argues that case study will need to play an increasingly important role
      in the evaluation of leadership development programmes as both formal and
      substantive theories of leadership place greater emphasis upon the role played by
      organizational context on leaders ability to bring about change. Prolonged
      engagement within a case study provides researchers with opportunities to capture
      the dynamics between leaders and their organisational contexts. However, adopting
      a case study approach is no substitute for inadequate theorization of the link
      between leadership approaches and leadership effects. The paper argues for the
      use of inclusive and expansive theoretical notions of leadership and its
      relationship to organisational context. The evaluation used to illustrate these
      arguments was based on a longitudinal multi-site case study methodology. The case
      studies ran over a three-year period and tracked the effect of 42 leaders on the
      quality of provision in some 30 early years settings. Both individual and
      collective theoires of leadership were used to trace leaders' steps, paths and
      routes to improvement. Three overlapping theoretical lenses were used to study
      the dynamics of these leaders interactions with a key aspect of their
      organisational contexts - the existing formal and informal leadership structures 
      and how these affected their attempts to improve the quality of provision of
      their settings. The analysis, and related findings, were tiered in order to
      provide progressively more detailed descriptions of the relationships between
      leaders' approaches and changes in their settings' quality of provision. Each
      layer of analysis operated with a causal logic that became gradually less general
      and linear and increasingly more 'local' and complex.

PMID- 29353147
TI  - Prediction of conserved sites and domains in glycoproteins B, C and D of herpes
      viruses.
AB  - Glycoprotein B (gB), C (gC) and D (gD) of herpes simplex virus are implicated in
      virus adsorption and penetration. The gB, gC and gD are glycoproteins for
      different processes of virus binding and attachment to the host cells. Moreover,
      their expression is necessary and sufficient to induce cell fusion in the absence
      of other glycoproteins. Egress of herpes simplex virus (HSV) and other herpes
      viruses from cells involves extensive modification of cellular membranes and
      sequential envelopment, de-envelopment and re-envelopment steps. Viral
      glycoproteins are important in these processes, and frequently two or more
      glycoproteins can largely suffice in any step. Hence, we target the 3 important
      glycoproteins (B, C and D) of eight different herpes viruses of different
      species. These species include human (HSV1 and 2), bovine (BHV1), equine (EHV1
      and 4), chicken (ILT1 and MDV2) and pig (PRV1). By applying different
      bioinformatics tools, we highlighted the conserved sites in these glycoproteins
      which might be most significant regarding attachment and infection of the
      viruses. Moreover the conserved domains in these glycoproteins are also
      highlighted. From this study, we will able to analyze the role of different viral
      glycoproteins of different species during herpes virus adsorption and
      penetration. Moreover, this study will help to construct the antivirals that
      target the glycoproteins of different herpes viruses.

PMID- 29353148
TI  - Light and electron microscopic observations on the organization of skin and
      associated glands of two caecilian amphibians from Western Ghats of India.
AB  - We adopted light and electron microscopy to understand the structure of the skin
      of two species of caecilians, Ichthyophis tricolor and Uraeotyphlus cf. oxyurus,
      from Western Ghats of Kerala, India. The surface of the skin of these caecilians
      contains an irregular pattern of microridges. Oval, round and polymorphic
      glandular openings are randomly distributed all over the skin surface. Most of
      the openings are funnel shaped. The epithelial cells along the rim of the opening
      descend into the tunnel of the duct. A few glandular openings protrude slightly
      above the epithelium of the duct. The skin is formed of epidermis and dermis.
      Small flat disk-like dermal scales, composed of a basal plate of several layers
      of unmineralized collagen fibers topped with a discontinuous layer of mineralized
      globular squamulae, are lodged in pouches in the transverse ridges of the skin.
      Each pouch contains 1-4 scales, which might differ in size. The scales are almost
      similar between species, yet the difference can be useful in distinguishing
      between the two species. Flask cells and Merkel cells are present in the
      epidermis. Two types of glands, mucous and granular, are present in the dermis.
      The mucous glands are densely packed with mucous vesicles. Darkly stained mucous
      producing cells are located around the periphery of the gland. Secretory mucous
      vesicles differ in their organization and distribution. The granular glands are
      located perpendicular to the skin surface. The granule producing cells of the
      gland are located near the periphery. There are differently stained spherical
      secretory granules of various sizes in the cytoplasm. Thus, the use of different
      microscopic techniques contributed fascinatingly to the first ever understanding
      of organization of the skin of two selected caecilian species from Western Ghats,
      revealing certain features to differ between them.

PMID- 29353149
TI  - Different ways to balance the spine in sitting: Muscle activity in specific
      postures differs between individuals with and without a history of back pain in
      sitting.
AB  - BACKGROUND: Previous research explored muscle activity in four distinct sitting
      postures with fine-wire electromyography, and found that lumbar multifidus muscle
      activity increased incrementally between sitting with flat thoracolumbar and
      lumbar regions, long thoracolumbar lordosis, or short lordosis confined to the
      lumbar region. This study used similar methods to explore whether people with a
      history of low back pain provoked by prolonged sitting used different patterns of
      trunk muscle activity in specific postures. METHODS: Fine-wire electromyography
      electrodes were inserted into the right lumbar multifidus (deep and superficial),
      iliocostalis (lateral and medial), longissimus thoracis and transversus abdominis
      muscles. Superficial abdominal muscle activity was recorded with surface or fine
      wire electrodes. Electromyography amplitude was compared between postures for the
      back pain group and observations were contrasted with the changes previously
      reported for pain-free controls. For comparison between groups normalised and non
      normalised electromyography amplitudes were compared. FINDINGS: Individuals with
      a history of back pain demonstrated greater activity of the longissimus thoracis
      muscle in the long lordosis compared with the flat posture [mean difference (95%
      CI): 46.6 (17.5-75.7)%, normalised to sitting posture peak activity], but pain
      free participants did not [mean difference: 7.7 (minus 12-27.6)%]. Pain-free
      participants modulated lumbar multifidus activity with changes in lumbar curve,
      but people with a history of pain in prolonged sitting did not change multifidus
      activity between the long and short lordotic postures. INTERPRETATION: In
      clinical ergonomic interventions that modify spinal curves and sagittal balance
      in sitting, the muscle activity used in those postures may differ between people
      with and without a history of back pain.

PMID- 29353150
TI  - Biodegradable spacer reduces the subacromial pressure: A biomechanical cadaver
      study.
AB  - BACKGROUND: Failure after rotator cuff repair remains a major clinical problem
      and could be related to excessive pressures from the acromion. Previous studies
      with irreparable tears showed good clinical results of tendon healing with
      arthroscopic insertion of a protective biodegradable spacer balloon between the
      repaired tendon and the acromion. One hypothesis is that compression pressures on
      the repaired tendon will be reduced by the spacer. This cadaver study aimed to
      investigate the effects of this subacromial spacer on compression pressures over
      a repaired supraspinatus tendon in passive motion. METHODS: Rotator cuff tear and
      repair were performed in six fresh-frozen cadaveric shoulders, followed by
      insertion of a biodegradable subacromial spacer. Specimens were tested using a
      passive shoulder simulator for abduction-adduction, flexion-extension and
      internal-external rotations. A sensor positioned below the acromion was used to
      measure compression pressure changes through passive range of motion before and
      after placement of a subacromial spacer. Peak pressures were measured in
      adduction-abduction motion, near 90 degrees  abduction. FINDINGS: Both the mean
      and peak pressures in abduction-adduction were significantly reduced after
      insertion of the subacromial spacer (from mean 121.7 (SD 9.5) MPa to 51.5 (SD
      1.2) MPa and from peak 1749.6 (SD 80.7) MPa to 535.1 (SD 27.6) MPa) (P<0.0001).
      INTERPRETATION: The reduced peak pressures and wider load distributions over the
      sensor during both passive abduction-adduction and flexion-extension motions
      suggest that the use of the spacer will lead to reduced wear of the repair in
      patients, and potentially prevent rotator cuff re-tear after surgical repair.

PMID- 29353151
TI  - The association between recreational physical activity, sedentary time, and
      colorectal polyps in a population screened for colorectal cancer.
AB  - PURPOSE: Regular recreational moderate to vigorous physical activity (rMVPA) has
      been previously associated with a reduced risk of colorectal cancer (CRC),
      however, few studies have examined the association of rMVPA with colorectal
      polyps, the pre-malignant precursor lesions. The objective of this study was to
      examine the associations between physical activity and sitting time and polyps at
      the time of screening. METHODS: We conducted a cross-sectional study of 2496
      individuals undergoing screening-related colonoscopy in Calgary, Alberta, Canada.
      Physical activity and sitting time were characterized using hours of rMVPA,
      meeting physical activity recommendations and hours of sitting time using self
      reported data obtained from the International Physical Activity Questionnaire.
      Logistic regression models were used to estimate the crude and adjusted odds
      ratios (OR) for presence of polyps associated with rMVPA and sitting time.
      RESULTS: Meeting physical activity guidelines of >=150 min/week was non
      significantly associated with a modest decrease in odds of having >=1 polyp at
      screening (ORadj = 0.95, 95% CI: 0.80-1.14). In males, threshold effects for
      sitting time were observed for up to 20 h/week (ORadj per hour sitting = 1.07,
      95% CI: 1.01-1.13). In stratified analysis, larger inverse associations were
      observed between physical activity and the presence of polyps in females, obese
      individuals, and ever smokers, compared to pooled findings. CONCLUSIONS: In this
      large CRC screening population, there was a suggestive association between
      increased rMVPA and reduced prevalence of polyps at screening, particularly among
      females. Even low amounts of regular sitting time (0-20 h/day) were associated
      with the presence of polyps, particularly among males. Further research on rMVPA
      and sitting time is necessary to better inform strategies to reduce the frequency
      of pre-malignant colorectal lesions.

PMID- 29353152
TI  - TGFbeta C-509T, TGFbeta T869C, XRCC1 Arg194Trp, IKBalpha C642T, IL4 C-590T
      Genetic polymorphisms combined with socio-economic, lifestyle, diet factors and
      gastric cancer risk: A case control study in South Indian population.
AB  - BACKGROUND: Gastric cancer is worldwide the third major cause of cancer related
      death. Risk factors for gastric cancer includes Helicobacter pylori infection,
      gastric ulcer, less hygienic condition, use of tobacco, alcohol consumption, use
      of salted, smoked food, genetic alterations etc. In order to identify the risk
      factors associated with gastric cancer in South Indian population a case-control
      study involving 200 proven gastric cancer cases and 400 controls was conducted.
      METHODS: A structured questionnaire was used to interview all the subjects who
      participated in our study. Genotyping assay was performed using Taqman allelic
      discrimination assay for 5 Single Nucleotide Polymorphisms (SNPs)-TGFbeta C-509T,
      TGFbeta T869C, XRCC1 Arg194Trp, IkBalpha C642T and IL4C-590T. RESULTS: Odds
      Ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional
      logistic regression. Statistical analysis on socio-economic factors, lifestyle
      factors had showed that subjects from low socio economic status, use of tobacco
      and consumption of non-vegetarian food had increased risk of developing gastric
      cancer. Multi-factorial analysis for the SNPs adjusting for the risk factors
      obtained in this study showed that TGFBeta C-509T TT genotypes had four fold
      increased risk of gastric cancer (OR = 4.11, CI = 1.02-16.56) and TGFbeta T869C
      CC genotype had a decreased risk of gastric cancer (OR = 0.21, CI = 0.05-0.85).
      CONCLUSION: Economic status, tobacco use and food habits play a significant role
      in gastric cancer development. TT genotype for TGFbeta C-509T had an increased
      risk and CC genotype for TGFbeta T869C had a decreased risk of gastric cancer in
      south Indian population after adjusting for socio-economic factors and lifestyle
      factors.

PMID- 29353153
TI  - Productivity losses due to premature mortality from cancer in Brazil, Russia,
      India, China, and South Africa (BRICS): A population-based comparison.
AB  - BACKGROUND: Over two-thirds of the world's cancer deaths occur in economically
      developing countries; however, the societal costs of cancer have rarely been
      assessed in these settings. Our aim was to estimate the value of productivity
      lost in 2012 due to cancer-related premature mortality in the major developing
      economies of Brazil, the Russian Federation, India, China and South Africa
      (BRICS). METHODS: We applied an incidence-based method using the human capital
      approach. We used annual adult cancer deaths from GLOBOCAN2012 to estimate the
      years of productive life lost between cancer death and pensionable age in each
      country, valued using national and international data for wages, and workforce
      statistics. Sensitivity analyses examined various methodological assumptions.
      RESULTS: The total cost of lost productivity due to premature cancer mortality in
      the BRICS countries in 2012 was $46.3 billion, representing 0.33% of their
      combined gross domestic product. The largest total productivity loss was in China
      ($28 billion), while South Africa had the highest cost per cancer death
      ($101,000). Total productivity losses were greatest for lung cancer in Brazil,
      the Russian Federation and South Africa; liver cancer in China; and lip and oral
      cavity cancers in India. CONCLUSION: Locally-tailored strategies are required to
      reduce the economic burden of cancer in developing economies. Focussing on
      tobacco control, vaccination programs and cancer screening, combined with access
      to adequate treatment, could yield significant gains for both public health and
      economic performance of the BRICS countries.

PMID- 29353154
TI  - CD41 immune staining of micromegakaryocytes improves the diagnosis of
      myelodysplastic syndrome and differentiation from pancytopenia.
AB  - A morphometric analysis was performed on aspirated clots of bone marrow to
      identify the presence of micromegakaryocytes after immune staining with a
      monoclonal antibody raised against CD41. Quantitative and qualitative
      abnormalities of micromegakaryocytes were assessed based on both standard
      staining and CD41 immune staining. Micromegakaryocytes were largely detected in
      bone marrow from patients with myelodysplastic syndrome (MDS), while almost no
      micromegakaryocytes were present in aplastic anemia. CD41 immune staining clearly
      improved the efficiency of micromegakaryocyte detection under any conditions,
      showing strong potential as a tool for the auxiliary diagnosis of MDS and
      differentiation of MDS from pancytopenia, particularly aplastic anemia(AA).

PMID- 29353155
TI  - Isolation, purification, structural characterization and immunostimulatory
      activity of water-soluble polysaccharides from Lepidium meyenii.
AB  - A water-soluble polysaccharide LMP-1 was isolated and purified by ion-exchange
      chromatography from maca (Lepidium meyenii Walp.). LMP-1 has a molecular weight
      of 1.01 * 104 Da, and is composed of glucose and arabinose with a molar ratio of
      7.03:1.08. Methylation and the 1D and 2D NMR spectroscopy of LMP-1 revealed that
      it is mainly composed of ->4)-alpha-D-Glcp-(1->, ->6)-alpha-D-Glcp-(1->, ->3)
      alpha-D-Glcp-(1->, and beta-D-Araf-(1->, with branching at O-6 of ->4,6)-alpha-D
      Glcp-(1 -> . LMP-1 showed up-regulation of Toll-like receptor 4 (TLR4) and Toll
      like receptor 2 (TLR2). The upstream proteins of Toll-like receptors (TLRs) (CD14
      and MD2) and mRNA level of IL-1beta also increased. Increased transcription
      factor nuclear factor-kappa B (NF-kappaB) p65 was found in the nuclei and
      cytoplasm in LMP-1-treated RAW264.7 macrophages. These results indicated that LMP
      1 activated RAW264.7 macrophages and elicited immunostimulatory activities via
      the TLRs/NF-kappaB signalling pathway.

PMID- 29353156
TI  - Sesquiterpenoids from Artemisia vestita.
AB  - Eleven previously undescribed sesquiterpenoids, arvestolides D-J, arvestonates A
      C, and arvestonol were isolated from the aerial parts of Artemisia vestita W.
      Their structures were elucidated by extensive analysis of HRMS, UV, IR, and NMR
      spectroscopic data, and the absolute configurations were determined by single
      crystal X-ray diffraction, empirical rules, and comparison of calculated and
      experimental ECD data. Arvestolides H and I showed inhibitory effects on nitric
      oxide production in BV-2 cells induced by lipopolysaccharide with IC50 values of
      43.2 and 39.9 MUM, respectively.

PMID- 29353157
TI  - Phytochemical analysis of salal berry (Gaultheria shallon Pursh.), a
      traditionally-consumed fruit from western North America with exceptionally high
      proanthocyanidin content.
AB  - Salal (Gaultheria shallon Pursh.) is a wild perennial shrub of the Ericaceae and
      common in coastal forests of western North America, and its berries were an
      important traditional food for First Nations in British Columbia. Salal berries
      were investigated for phytochemical content and antioxidant capacity over the
      course of fruit development. The proanthocyanidin content was extremely high in
      young berries (280.7 mg/g dry wt) but dropped during development to 52.8 mg/g dry
      wt. By contrast, anthocyanins accumulated only at the late berry stages. Total
      antioxidant capacity, as measured by the 2,2'-azinobis-(3-ethylbenzothiazoline-6
      sulfonic acid (ABTS) method, reflected both proanthocyanidin and anthocyanin
      content, and in mature berries reached 36 mmol Trolox equivalents/100 g dry wt.
      More detailed phytochemical analysis determined that delphinidin 3-O-galactoside
      is the dominant anthocyanin, and that the berries are also rich in procyanidins,
      including procyanidin A2 which has been implicated in anti-adhesion activity for
      uropathogenic E. coli. Proanthocyanidins were 60% prodelphinidin, and overall
      concentrations were higher than reported for many Vaccinium species including
      blueberry, lingonberry, and cranberry. Overall, the phenolic profile of salal
      berries indicates that these fruit contain a diversity of health-promoting
      phenolics.

PMID- 29353159
TI  - Trauma, attentional dysregulation, and the development of posttraumatic stress:
      An investigation of risk pathways.
AB  - BACKGROUND: Fundamental questions regarding the nature and function of
      attentional bias (AB) to threat in the etiology of posttraumatic stress disorder
      (PTSD) remain unanswered. We tested the temporal interplay between trauma
      exposure, dysregulated attentional processing of threatening information pre- and
      post-trauma, and the development of posttraumatic intrusions. METHODS: Response
      time to trauma-related threat, trauma-unrelated threat, as well as to trauma
      related but typically emotionally-neutral stimuli was assessed using the dot
      probe task before and one week after watching a violent movie scene that served
      as a trauma analogue. AB was analyzed as a dynamic process by means of a recently
      developed approach indexing momentary fluctuations of AB toward and away from
      emotional stimuli. Posttraumatic intrusions were measured daily over the week
      following analogue trauma exposure. RESULTS: We found that key features of AB
      dynamics to trauma-related stimuli at post-, but not pre-, trauma exposure were
      associated with posttraumatic intrusions. Notably, these post-trauma exposure
      effects were specific to biased attentional processing of trauma-related but not
      threatening stimuli unrelated to the traumatic event. In line with a growing body
      of findings, pre- and post-trauma exposure traditional aggregated mean AB scores
      were not similarly associated with posttraumatic intrusions. CONCLUSIONS: We
      conclude that one mechanism through which trauma exposure may contribute to the
      development of PTSD is through its dysregulation of attentional processing of
      trauma event-related cues. Future work may focus on delineating the developmental
      course through which attentional dysregulation post-trauma and posttraumatic
      intrusions unfold and interact.

PMID- 29353158
TI  - Quantification of light-induced miniSOG superoxide production using the selective
      marker, 2-hydroxyethidium.
AB  - Genetically-encoded photosensitizers produce reactive oxygen species (ROS) in
      response to light. Transgenic expression of fusion proteins can target the
      photosensitizers to specific cell regions and permit the spatial and temporal
      control of ROS production. These ROS-generating proteins (RGPs) are widely used
      for cell ablation, mutagenesis and chromophore-assisted light inactivation of
      target proteins. However, the species produced by RGPs are unclear due to
      indirect measures with confounding interpretations. Recently, the RGP mini
      "Singlet Oxygen Generator" (miniSOG) was engineered from Arabidopsis thaliana
      phototropin 2. While miniSOG produces singlet oxygen (1O2), the contribution of
      superoxide (O2*-) to miniSOG-generated ROS remains unclear. We measured the light
      dependent O2*- production of purified miniSOG using HPLC separation of
      dihydroethidium (DHE) oxidation products. We demonstrate that DHE is insensitive
      to 1O2 and establish that DHE is a suitable indicator to measure O2*- production
      in a system that produces both 1O2 and O2*-. We report that miniSOG produces both
      1O2 and O2*-, as can its free chromophore, flavin mononucleotide. miniSOG
      produced O2*- at a rate of ~4.0umol O2*-/min/umol photosensitizer for an
      excitation fluence rate of 5.9mW/mm2 at 470 +/- 20nm, and the rate remained
      consistent across fluences (light doses). Overall, the contribution of O2*- to
      miniSOG phenotypes should be considered.

PMID- 29353160
TI  - Prediction of venous thromboembolism using semantic and sentiment analyses of
      clinical narratives.
AB  - Venous thromboembolism (VTE) is the third most common cardiovascular disorder. It
      affects people of both genders at ages as young as 20 years. The increased number
      of VTE cases with a high fatality rate of 25% at first occurrence makes
      preventive measures essential. Clinical narratives are a rich source of knowledge
      and should be included in the diagnosis and treatment processes, as they may
      contain critical information on risk factors. It is very important to make such
      narrative blocks of information usable for searching, health analytics, and
      decision-making. This paper proposes a Semantic Extraction and Sentiment
      Assessment of Risk Factors (SESARF) framework. Unlike traditional machine
      learning approaches, SESARF, which consists of two main algorithms, namely,
      ExtractRiskFactor and FindSeverity, prepares a feature vector as the input to a
      support vector machine (SVM) classifier to make a diagnosis. SESARF matches and
      maps the concepts of VTE risk factors and finds adjectives and adverbs that
      reflect their levels of severity. SESARF uses a semantic- and sentiment-based
      approach to analyze clinical narratives of electronic health records (EHR) and
      then predict a diagnosis of VTE. We use a dataset of 150 clinical narratives, 80%
      of which are used to train our prediction classifier support vector machine, with
      the remaining 20% used for testing. Semantic extraction and sentiment analysis
      results yielded precisions of 81% and 70%, respectively. Using a support vector
      machine, prediction of patients with VTE yielded precision and recall values of
      54.5% and 85.7%, respectively.

PMID- 29353161
TI  - Automated diagnosis of focal liver lesions using bidirectional empirical mode
      decomposition features.
AB  - Liver is the heaviest internal organ of the human body and performs many vital
      functions. Prolonged cirrhosis and fatty liver disease may lead to the formation
      of benign or malignant lesions in this organ, and an early and reliable
      evaluation of these conditions can improve treatment outcomes. Ultrasound imaging
      is a safe, non-invasive, and cost-effective way of diagnosing liver lesions.
      However, this technique has limited performance in determining the nature of the
      lesions. This study initiates a computer-aided diagnosis (CAD) system to aid
      radiologists in an objective and more reliable interpretation of ultrasound
      images of liver lesions. In this work, we have employed radon transform and bi
      directional empirical mode decomposition (BEMD) to extract features from the
      focal liver lesions. After which, the extracted features were subjected to
      particle swarm optimization (PSO) technique for the selection of a set of
      optimized features for classification. Our automated CAD system can differentiate
      normal, malignant, and benign liver lesions using machine learning algorithms. It
      was trained using 78 normal, 26 benign and 36 malignant focal lesions of the
      liver. The accuracy, sensitivity, and specificity of lesion classification were
      92.95%, 90.80%, and 97.44%, respectively. The proposed CAD system is fully
      automatic as no segmentation of region-of-interest (ROI) is required.

PMID- 29353162
TI  - Monolayers of a tetrazine-containing gemini amphiphile: Interplays with
      biomembrane lipids.
AB  - The property of a newly synthesized tetrazine derivative comprised of double C18
      saturated hydrocarbon chain (C18-rTz-C18) has been studied in situ at the air
      water interface. C18-rTz-C18 or a gemini amphiphile contributes to restriction of
      its tetrazine moiety on the interface, which is expected to be used for
      bioimaging and analytical reagents. Herein, to understand lateral interactions
      between Tz and biomembrane constituents, we investigated the interfacial behavior
      of Langmuir monolayers composed of C18-rTz-C18 and biomembrane lipids such as
      DPPC, DPPG, DPPE, PSM, and Cholesterol (Ch). The lateral interaction of the
      binary monolayers was analyzed with the surface pressure (pi)-molecular area (A)
      and surface potential (DeltaV)-A isotherms. These thermodynamic data indicate
      that all of the two-components are miscible with each other. In particular, as
      opposed to the others, the monolayer stability of DPPE, which is a major
      constituent of the inner surface of cell membranes, is attenuated by the small
      amount addition of C18-rTz-C18. This specific interaction implies the membrane
      destruction from the inside. The phase behavior during monolayer compression was
      visualized with Brewster angle microscopy (BAM), fluorescence microscopy (FM),
      and atomic force microscopy (AFM). The obtained morphologies exhibit a
      coexistence state of two different liquid-condensed domains derived from extra
      phospholipids and phospholipids-C18-rTz-C18 monolayers.

PMID- 29353163
TI  - Time interval between neoadjuvant chemoradiotherapy and surgery for oesophageal
      or junctional cancer: A nationwide study.
AB  - INTRODUCTION: The optimal time between end of neoadjuvant chemoradiotherapy
      (nCRT) and oesophagectomy is unknown. The aim of this study was to assess the
      association between this interval and pathologic complete response rate (pCR),
      morbidity and 30-day/in-hospital mortality. METHODS: Patients with oesophageal
      cancer treated with nCRT and surgery between 2011 and 2016 were selected from a
      national database: the Dutch Upper Gastrointestinal Cancer Audit (DUCA). The
      interval between end of nCRT and surgery was divided into six periods: 0-5 weeks
      (n = 157;A), 6-7 weeks (n = 878;B), 8-9 weeks (n = 972;C), 10-12 weeks (n =
      720;D), 13-14 weeks (n = 195;E) and 15 or more weeks (n = 180;F). The association
      between these interval groups and outcomes was investigated using univariable and
      multivariable analysis with group C (8-9 weeks) as reference. RESULTS: In total,
      3102 patients were included. The pCR rate for the groups A to F was 31%, 28%,
      26%, 31%, 40% and 37%, respectively. A longer interval was associated with a
      higher probability of pCR (>=10 weeks for adenocarcinoma: odds ratio [95%
      confidence interval]: 1.35 [1.00-1.83], 1.95 [1.24-3.07], 1.64 [0.99-2.71] and
      >=13 weeks for squamous cell carcinoma: 2.86 [1.23-6.65], 2.67 [1.29-5.55].
      Patients operated >=10 weeks after nCRT had the same probability for
      intraoperative/postoperative complications. Patients from groups D and F had a
      higher 30-day/in-hospital mortality (1.80 [1.08-3.00], 3.19 [1.66-6.14]).
      CONCLUSION: An interval of >=10 weeks for adenocarcinoma and >=13 weeks for
      squamous cell carcinoma between nCRT and oesophagectomy was associated with a
      higher probability of having a pCR. Longer intervals were not associated with
      intraoperative/postoperative complications. The 30-day/in-hospital mortality was
      higher in patients with extended intervals (10-12 and >=15 weeks); however, this
      might have been due to residual confounding.

PMID- 29353164
TI  - A phase II study of nab-paclitaxel in combination with ramucirumab in patients
      with previously treated advanced gastric cancer.
AB  - BACKGROUND: Nanoparticle albumin-bound (nab)-paclitaxel was developed to improve
      paclitaxel solubility and does not need premedication to avoid infusion-related
      reactions associated with solvent-based (sb)-paclitaxel. We conducted a phase II
      trial to investigate the efficacy and safety of nab-paclitaxel plus ramucirumab
      combination therapy for previously treated advanced gastric cancer. PATIENTS AND
      METHODS: Patients with unresectable advanced gastric cancer refractory to first
      line chemotherapy were administered nab-paclitaxel 100 mg/m2 intravenously on
      days 1, 8 and 15, plus ramucirumab 8 mg/kg intravenously on days 1 and 15 of a 28
      day cycle. The primary end-point was Independent Review Committee (IRC)-assessed
      overall response rate (ORR). Secondary end-points were progression-free survival
      (PFS), overall survival (OS), disease control rate (DCR), safety and quality of
      life (QOL). RESULTS: Forty-five patients were enrolled; 43 received the study
      treatment. The ORR assessed by the IRC was 54.8% (90% confidence interval [CI]
      41.0-68.0) and the primary end-point was met. The DCR was 92.9% (95% CI 80.5
      98.5). The IRC-assessed median PFS was 7.6 months (95% CI 5.4-8.1). The median OS
      was not reached at the data cutoff. The main treatment-related grade 3 or 4
      adverse events were decreased neutrophil count (76.7%), decreased white blood
      cell count (27.9%), anaemia (11.6%), decreased appetite (7.0%), febrile
      neutropenia (4.7%), hypertension (4.7%) and proteinuria (4.7%). No treatment
      related deaths occurred. No QOL deterioration was observed during study
      treatment. CONCLUSION: Nab-paclitaxel plus ramucirumab combination therapy shows
      promising activity and manageable toxicities and could be a useful second-line
      treatment option for patients with previously treated advanced gastric cancer.

PMID- 29353165
TI  - Prognostic value of primary tumour resection in synchronous metastatic colorectal
      cancer: Individual patient data analysis of first-line randomised trials from the
      ARCAD database.
AB  - Indication for primary tumour resection (PTR) in asymptomatic metastatic
      colorectal cancer (mCRC) patients is unclear. Previous retrospective analyses
      suggest a survival benefit for patients who underwent PTR. The aim was to
      evaluate the prognostic value of PTR in patients with synchronous mCRC by
      analysis of recent large RCTs including systemic therapy with modern targeted
      agents. Individual patient data (IPD) of 3423 patients enrolled into 8 randomised
      controlled trials (RCTs) with first-line systemic therapy in the ARCAD (Aide et
      Recherche en Cancerologie Digestive) database were analysed. The number of
      patients with unresected synchronous mCRC, resected synchronous mCRC and
      metachronous mCRC was 710 (21%), 1705 (50%) and 1008 (29%), respectively.
      Adjusting for age, gender, performance status (PS) and prior chemotherapy, the
      unresected group had a significantly worse median overall survival (16.4 m)
      compared with the synchronous resected (22.2 m; hazard ratio [HR] 1.60, 95% CI
      1.43-1.78) and metachronous (22.4 m; HR 1.81, 95% CI 1.58-2.07) groups.
      Similarly, median progression-free survival was significantly worse for the
      unresected group compared with the synchronous resected (HR 1.31, 95% CI 1.19
      1.44) and metachronous (HR 1.47, 95% CI 1.30-1.66) groups. In a multivariate
      analysis, the observed associations remained significant. This largest IPD
      analysis of mCRC trials to date demonstrates an improved survival in synchronous
      mCRC patients after PTR. These results may be subject to bias since reasons for
      (non)resection were not available. Until results of ongoing RCTs are available,
      both upfront PTR followed by systemic treatment and upfront systemic treatment
      are considered appropriate treatment strategies.

PMID- 29353166
TI  - Toxicological responses on cytochrome P450 and metabolic transferases in liver of
      goldfish (Carassius auratus) exposed to lead and paraquat.
AB  - As the producer of reactive oxygen species (ROS), both lead (Pb) and paraquat
      (PQ) can generate serious oxidative stress in target organs which result in
      irreversible toxic effects on organisms. They can disturb the normal catalytic
      activities of many enzymes by means of different toxicity mechanism. The changed
      responses of enzymes are frequently used as the biomarkers for indicating the
      relationship between toxicological effects and exposure levels. In this work,
      goldfish was exposed to a series of test groups containing lead and paraquat in
      the range of 0.05-10mg/L, respectively. Four hepatic enzyme activities, including
      7-ethoxyresorufinO-deethylase (EROD), 7-benzyloxy-4-trifluoromethyl-coumarin-O
      debenzyloxylase (BFCOD), glutathione S-transferase (GST) and UDP
      glucuronosyltransferase (UGT) were determined after 1, 7, 14, 28 days exposure.
      The results showed that the activities of EROD and BFCOD in fish were
      significantly inhibited in response to paraquat at all exposure levels during the
      whole experiment. Similarly, the inhibitory effects of lead exposure on BFCOD
      activity were found in our study, while different responses of lead on EROD were
      observed. There were no significant differences on EROD activity under lower
      concentrations of lead (less than 0.1mg/L) before 14 days until an obvious
      increase was occurred for the 0.5mg/L lead treatment group at day 14.
      Furthermore, lead showed stronger inhibition on GST activity than paraquat when
      the concentrations of the two toxicants were more than 0.5mg/L. However, the
      similar dose and time-dependent manners of UGT activity were found under lead and
      paraquat exposure. Our results indicated that higher exposure levels and longer
      accumulations caused inhibitory effects on the four enzymes regardless of lead or
      paraquat stress. In addition, the responses of phase I enzymes were more
      sensitive than that of phase II enzymes and they may be served as the acceptable
      biomarkers for evaluating the toxicity effects of both lead and paraquat.

PMID- 29353167
TI  - Eco- and genotoxicity profiling of a rapeseed biodiesel using a battery of
      bioassays.
AB  - Biodiesel is considered an important renewable energy source but still there is
      some controversy about its environmental toxicity, especially to aquatic life. In
      our study, the toxicity of water soluble fraction of biodiesel was evaluated in
      relatively low concentrations using a battery of bioassays: Vibrio fischeri
      bioluminescence inhibition, Sinapis alba root growth inhibition, Daphnia magna
      immobilization, boar semen live/dead ratio and DNA fragmentation and Unio
      pictorum micronucleus test. While the S. alba test indicated nutritive
      (stimulating) effect of the sample, the biodiesel exerted toxic effect in the
      aquatic tests. D. magna was the most sensitive with EC50 value of 0.0226%. For
      genotoxicity assessment, the mussel micronucleus test (MNT) was applied,
      detecting considerable genotoxic potential of the biodiesel sample: it elucidated
      micronuclei formation already at low concentration of 3.3%. Although this test
      has never been employed in biodiesel eco/genotoxicity assessments, it seems a
      promising tool, based on its appropriate sensitivity, and representativity.

PMID- 29353168
TI  - Zinc and lead detoxifying abilities of humic substances relevant to environmental
      bacterial species.
AB  - The effect of humic substances (HS) and their different fractions (humic acids
      (HA) and hymatomelanic acids (HMA)) on the toxicity of zinc and lead to different
      strains of bacteria was studied. All tested bacteria demonstrated a lower
      resistance to zinc than lead showing minimum inhibitory concentrations of 0.1 -
      0.3mM and 0.3-0.5mM, respectively. The highest resistance to lead was
      characteristic of Pseudomonas chlororaphis PCL1391 and Rhodococcus RS67, while
      Pseudomonas chlororaphis PCL1391 showed the greatest resistance to zinc. The
      combined fractions of HS and HA alone reduced zinc toxicity at all added
      concentrations of the organic substances (50 - 200mgL-1) to all microorganisms,
      while hymatomelanic acids reduced zinc toxicity to Pseudomonas chlororaphis
      PCL1391 at 200mgL-1 organic concentration only. The HS fractions imparted similar
      effects on lead toxicity also. This study demonstrated that heavy metal toxicity
      to bacteria could be reduced through complexation with HS and their fractions.
      This was particularly true when the metal-organic complexes held a high
      stability, and low solubility and bioavailability.

PMID- 29353169
TI  - Integrated biomarkers response confirm the antioxidant role of diphenyl
      diselenide against atrazine.
AB  - Atrazine (ATZ) is a herbicide worldwide used. That can cause oxidative damage in
      non-target organisms, such as fish. Furthermore, the threat of exposure to
      pesticides together with poor nutrition is hazardous to the normal development of
      fish, and supplementation of the fish diet with antioxidants compounds is an
      alternative approach to prevent the hazardous effects of pesticide exposure. Here
      we aimed to investigate the capacity of diphenyl diselenide (PhSe)2 diet
      supplementation to improve the antioxidant defense of Cyprinus carpio (carp)
      exposed to environmental concentrations of ATZ. To prove the efficiency of
      (PhSe)2, we used the Integrated Biomarkers Response (IBR) methodology. Therefore,
      carp were fed for 8 weeks diets either with or without (PhSe)2 and exposed to 2
      or 10ug/L of ATZ for 96h, euthanized, and their liver, gills, and muscle tissues
      were removed for biochemical assays. ATZ was able to cause oxidative damage from
      reactive species production in all tissues of carp, as observed by the increase
      of lipid peroxidation and protein damage. The activity of some antioxidant
      enzymes was inhibited in carp exposed to ATZ. However, (PhSe)2 supplementation
      was able to prevent this ATZ-induced damage by improving the activities of
      antioxidant enzymes and through antioxidant competence of (PhSe)2per se.
      Furthermore, IBR was shown to be a useful tool to compare treatments, even at
      different concentrations, and identify the efficiently antioxidant behavior of
      the organoselenium compound.

PMID- 29353170
TI  - Transgenerational effects of ocean warming on the sea urchin Strongylocentrotus
      intermedius.
AB  - Transgenerational effects, which involve both selection and plasticity, are
      important for the evolutionary adaptation of echinoderms in the changing ocean.
      Here, we investigated the effects of breeding design and water temperature for
      offspring on fertilization, hatchability, larval survival, size, abnormality and
      metamorphosis of the sea urchin Strongylocentrotus intermedius, whose dams and
      sires were exposed to long-term (~15 months) elevated temperature (~3 degrees C
      above ambient) or ambient temperature. There was no transgenerational effect on
      fertilization and metamorphosis of S. intermedius, while negative
      transgenerational effects were found in hatchability and most traits of larval
      size. Dam and sire effects were highly trait and developmental stage dependent.
      Interestingly, we found S. intermedius probably cannot achieve transgenerational
      acclimation to long-term elevated temperature for survival provided their
      offspring were exposed to an elevated temperature. The present study enriches our
      understanding of transgenerational effects of ocean warming on sea urchins.

PMID- 29353171
TI  - Microcystin-LR nanobody screening from an alpaca phage display nanobody library
      and its expression and application.
AB  - Microcystin-LR (MC-LR) is a type of biotoxin that pollutes the ecological
      environment and food. The study aimed to obtain new nanobodies from phage
      nanobody library for determination of MC-LR. The toxin was conjugated to keyhole
      limpet haemocyanin (KLH) and bovine serum albumin (BSA), respectively, then the
      conjugates were used as coated antigens for enrichment (coated MC-LR-KLH) and
      screening (coated MC-LR-BSA) of MC-LR phage nanobodies from an alpaca phage
      display nanobody library. The antigen-specific phage particles were enriched
      effectively with four rounds of biopanning. At the last round of enrichment,
      total 20 positive monoclonal phage nanobodies were obtained from the library,
      which were analyzed after monoclonal phage enzyme linked immunosorbent assay
      (ELISA), colony PCR and DNA sequencing. The most three positive nanobody genes,
      ANAb12, ANAb9 and ANAb7 were cloned into pET26b vector, then the nanobodies were
      expressed in Escherichia coli BL21 respectively. After being purified, the
      molecular weight (M.W.) of all nanobodies were approximate 15kDa with sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The purified
      nanobodies, ANAb12, ANAb9 and ANAb7 were used to establish the indirect
      competitive ELISA (IC-ELISA) for MC-LR, and their half-maximum inhibition
      concentrations (IC50) were 0.87, 1.17 and 1.47MUg/L, their detection limits
      (IC10) were 0.06, 0.08 and 0.12MUg/L, respectively. All of them showed strong
      cross-reactivity (CRs) of 82.7-116.9% for MC-RR, MC-YR and MC-WR, and weak CRs of
      less than 4.56% for MC-LW, less than 0.1% for MC-LY and MC-LF. It was found that
      all the IC-ELISAs for MC-LR spiked in tap water samples detection were with good
      accuracy, stability and repeatability, their recoveries were 84.0-106.5%,
      coefficient of variations (CVs) were 3.4-10.6%. These results showed that IC
      ELISA based on the nanobodies from the alpaca phage display antibody library were
      promising for high sensitive determination of multiple MCs.

PMID- 29353172
TI  - Bioaccumulation and sources of metal(loid)s in lilies and their potential health
      risks.
AB  - Dietary intake of metal(loid)s can seriously affect human health, but the levels,
      the bioaccumulation, sources and related health risks of As, Cd, Cr and Pb in
      cultivated lilies, particularly for Lilium davidii var. unicolor, remain
      unresolved. We collected 35 lily samples aged 1-6 years from farmlands of two
      types of soil (heilu soils and loessal soils) in Qilihe district in 2016 and
      analysed the concentrations of As, Cd, Cr and Pb in bulbs, the soil-bulb
      bioaccumulation and the potential sources of these elements in bulbs. Non
      carcinogenic and carcinogenic risks by consuming lilies were also assessed.
      Concentrations of four elements decreased in the order of Cr > Pb > Cd > As, and
      soil-bulb BCFs in the order of BCFCd > BCFCr > BCFPb > BCFAs. The Cd
      concentration of bulbs of lilies which grew in heilu soils was statistically
      higher than that of bulbs of lilies which grew in loessal soils, and the Cd
      concentration of bulbs of lilies aged 1-3 years was statistically higher than
      that of bulbs of lilies aged 4-6 years. Levels and soil-bulb BCFs of Cr and Pb of
      two-bulbed lilies were statistically higher than those of one-bulbed lilies.
      Farmyard manure may be a primary source of Cd in soil. There existed overall
      potential non-carcinogenic effects by exposure to the combination of four
      elements. Dietary intake of Cr posed carcinogenic risks to both adults and
      children. Non-carcinogenic and carcinogenic risks were higher for adults than
      children. Concluding, the edible parts of lily were significantly polluted by Cr
      and Pb but not by As and Cd. The number of bulbs significantly impacted
      concentrations and soil-bulb BCFs of Cr and Pb, but the reason for which needs
      further studies. Non-carcinogenic and carcinogenic risks caused by lily
      consumption should not be neglected.

PMID- 29353173
TI  - Use of Cu/Zn-superoxide dismutase tool for biomonitoring marine environment
      pollution in the Persian Gulf and the Gulf of Oman.
AB  - Superoxide dismutase (SOD) is the pivotal antioxidant enzyme that defends
      organisms against the oxidative stresses of superoxide radicals. In this
      experimental study, purification of SOD from the leaves of Avicennia marina (grey
      mangrove or white mangrove) from the family Acanthaceae, located in Sirik
      mangrove forest on the shore of the Gulf of Oman was performed, for the intended
      characterization of SOD. The Sirik AmSOD (A. marina SOD) expressed optimum
      activity in the pH range of 6-9 with the maximum activity at pH 8. The optimal
      temperature for Sirik AmSOD activity was 70 degrees C. Comparison of the pH and
      temperature optima in two regions (the Persian Gulf and the Gulf of Oman) showed
      significant differences with P<0.05. The SOD from the Persian Gulf was more
      resistant against the environmental stressors, because of the biochemical
      adaption to this environment, which is harsher. The evidence from these results
      suggests that AmSOD has different characteristics in each place, and mangroves
      undergo different adaptations and require different protections. The results of
      the enzymatic research can be useful for ecological management of organisms.

PMID- 29353174
TI  - Cholinesterase activity in the cup oyster Saccostrea sp. exposed to chlorpyrifos,
      imidacloprid, cadmium and copper.
AB  - In the present study, the sensitivity and concentration dependence of three
      functionally-defined components of cholinesterase activity (total: T-ChE; eserine
      sensitive: Es-ChE; and eserine-resistant: Er-ChE) were quantified in the gill,
      digestive gland and adductor muscle of the tropical cup oyster Saccostrea sp.,
      following acute (96h) aqueous exposure to commercial formulations of the
      organophosphate (OP) insecticide chlorpyrifos and the neonicotinoid (NN)
      imidacloprid (concentration range: 0.1-100mg/L), as well as to dissolved cadmium
      and copper (concentration range: 1-1000MUg/L). Oysters (1.5-5.0cm shell length),
      field-collected from a boating marina in Santa Marta, Colombia (Caribbean Sea)
      were exposed in the laboratory to each substance at five concentrations. T-ChE,
      Es-ChE, and Er-ChE activity were quantified in the three tissues in pools of 5
      individuals (3 replicates per concentration), before and after inhibition with
      the total cholinesterase inhibitor eserine (physostigmine, 100uM). Oysters
      exposed to chlorpyrifos, imidacloprid and Cd showed reduced T-ChE and Es-ChE
      activity in gills at highest exposure concentrations, with Es-ChE activity being
      inhibited proportionally more so than T-ChE, whereas Er-ChE activity showed no
      significant concentration-response. Digestive gland also showed diminished T-ChE,
      Es-ChE and Er-ChE activity for highest chlorpyrifos and Cd concentrations
      relative to controls, but an increase of T-ChE and Er-ChE activity at the highest
      imidacloprid concentration (100mg/L). For Cu, T-ChE, Es-ChE and Er-ChE activities
      in gills and digestive gland were elevated relative to controls in oysters
      exposed to Cu concentrations > 100ug/L. In adductor muscle, T-ChE, Es-ChE and Er
      ChE activity showed no apparent pattern for any of the four xenobiotics and
      concentration levels tested. Although this study confirms acute (96h)
      concentration-dependent reduction of tissue T-ChE and Es-ChE activity in gills
      and digestive glands of Saccostrea sp. exposed to high concentrations of
      chlorpyrifos (100mg/L), significant changes in T-ChE, Es-ChE and Er-ChE were also
      caused by exposure to Cd and Cu at concentrations > 100ug/L and by exposure to
      imidacloprid (100mg/L), indicating that cholinesterase activity is not a specific
      biomarker of organophosphate exposure in this species, but, rather, a biomarker
      of diverse xenobiotic exposure.

PMID- 29353175
TI  - Phyto-management of chromium contaminated soils through sunflower under
      exogenously applied 5-aminolevulinic acid.
AB  - Soil contamination with heavy metals is threatening the food security around the
      globe. Chromium (Cr) contamination results in poor quality and reduction in yield
      of crops. The present research was performed to figure out the Cr toxicity in
      sunflower and the ameliorative role of 5-aminolevulinic acid (ALA) as a plant
      growth regulator. The sunflower (FH-614) was grown under increasing concentration
      of Cr (0, 5, 10 and 20mgkg-1) alone and/or in combination with 5-ALA (0, 10 and
      20mgL-1). Results showed that Cr suppressed the overall growth, biomass, gas
      exchange attributes and chlorophyll content of sunflower plants. Moreover, lower
      levels of Cr (5 and 10mgkg-1) increased the production of reactive oxygen species
      (ROS) and electrolyte leakage (EL) along with the activities of antioxidant
      enzymes i.e., superoxide dismutase (SOD), guaiacole peroxidase (POD), ascorbate
      (APX), catalase (CAT). But at higher concentration of Cr (20mgkg-1), the
      activities of these enzymes presented a declining trend. However, the addition of
      5-ALA significantly alleviated the Cr-induced toxicity in sunflower plant and
      enhanced the plant growth and biomass parameters along with increased chlorophyll
      content, gas exchange attributes, soluble proteins and soil plant analysis
      development (SPAD) values by scavenging the ROS and lowering down the EL. The 5
      ALA also enhanced the activities of antioxidant enzymes at all levels of Cr. The
      increase in Cr concentration in all plant parts such as leaf, root and stem was
      directly proportional to the Cr concentration in soil. The application of 5-ALA
      further enhanced the uptake of Cr and its concentration in the plants. To
      understand this variation in response of plants to 5-ALA, detailed studies are
      required on plant biochemistry and genetic modifications.

PMID- 29353176
TI  - Predicting time to recall in patients conditionally released from a secure
      forensic hospital: A survival analysis.
AB  - BACKGROUND: The recall of conditionally discharged forensic patients in England
      is a formal order from the Ministry of Justice under the Mental Health Act (1983)
      which has the power to revoke conditional release and direct readmission to
      hospital. Recall has significant implications for the individual and for hospital
      services, but despite this, little is known about predictors of recall for
      forensic patients. METHODS: We examined the rate of recall for 101 patients
      conditionally discharged from medium secure forensic inpatient services between
      2007 and 2013. Demographic, clinical, and forensic factors were examined as
      possible predictors of time to recall using Cox regression survival techniques.
      RESULTS: Conditionally discharged patients were followed for an average of 811
      days, during which 45 (44.5%) were recalled to hospital. Younger age (HR 1.89;
      95% CI 1.02-3.49; p = 0.04), non-white ethnicity (HR 3.44; 95% CI 1.45-8.13),
      substance abuse history (HR 2.52; 95% CI 1.17-5.43), early violence (HR 1.90; 95%
      CI 1.03-3.50), early childhood maladjustment (HR 1.92; 95% CI 1.01-3.68),
      treatment with a depot medication (HR 2.17; 95% CI 1.14-4.11), being known to
      mental health services (HR 3.44; 95% CI 1.06-11.16), and a psychiatric admission
      prior to the index admission (HR 2.44; 95% CI 1.08-5.52) were significantly
      associated with a shorter time to recall. Treatment with clozapine reduced the
      risk of recall to hospital (HR 0.40; 95% CI 0.20-0.79). CONCLUSIONS: Time to
      recall can be predicted by a range of factors that are readily available to
      clinical teams. Further research is required to determine if targeted
      interventions can modify the likelihood or time to recall for conditionally
      released forensic patients.

PMID- 29353177
TI  - Psychiatric disorders and compliance with prenatal care: A 10-year retrospective
      cohort compared to controls.
AB  - BACKGROUND: Inadequate prenatal care has been associated with adverse perinatal
      outcomes. We sought to compare compliance with prenatal care visits (PCV), oral
      glucose tolerance test (OGTT) and serum alfa-fetoprotein (aFP) in women with
      psychiatric disorders (PD) and healthy controls. METHODS: Subjects were 5395
      women (1043 PD and 4352 controls), members of Clalit Health Services (Tel-Aviv
      district, Israel), who gave birth during 2004-2014. We used Generalized
      Estimating Equations with binary-logistic models, considering consecutive
      pregnancies as repeated measures with unbalanced design. The diagnostic subgroup
      was the main independent, assessed once with and once without age, socioeconomic
      status and multiple gestation variables. RESULTS: Risk for non-compliance with
      OGTT was increased in women with depression (aOR = 1.4, 95% CI = 1.1-1.7) and
      schizophrenia (aOR = 1.8, 95% CI = 1.1-2.9), but not anxiety. Risk for non
      compliance with aFP was decreased in women with anxiety (aOR = 0.6, 95% CI = 0.5
      0.8), but women with depression and schizophrenia did not differ from controls.
      PD were at risk for both absence of PCV (aOR = 4.6, 95% CI = 2.7-8.0) and high
      utilization of PCV (>20 visits, aOR = 2.8, 95% CI = 2.1-3.7).
      Psychopharmacological treatment during pregnancy was associated with high
      utilization of PCV (OR = 2.2, 95% CI = 1.7-2.9), increased compliance with aFP
      tests (OR = 1.4, 95% CI = 1.1-1.7) and marginally-significant increased
      compliance with OGTT (OR = 0.82, 95% CI = 0.67-1.01). CONCLUSION: PD under
      utilized tests perceived for the wellbeing of the mother (OGTT) and over-utilize
      tests for the wellbeing of the fetus (aFP). PD exhibited patterns of both very
      low and very high utilization of PCV. Psychopharmacological treatment during
      pregnancy may improve some measures of compliance with prenatal care.

PMID- 29353178
TI  - Impulsivity in early psychosis: A complex link with violent behaviour and a
      target for intervention.
AB  - BACKGROUND: Violent behaviour (VB) occurs in first episode of schizophrenia and
      can have devastating impact both on victims and patients themselves. A better
      knowledge of the underlying mechanisms of VB may pave the way to preventive
      treatments. OBJECTIVES: 1) To explore the nature of the link between impulsivity
      and VB in early psychosis (EP) patients; 2) To explore the interactions between
      impulsivity and substance abuse, insight, and positive symptoms, the main dynamic
      risk factors of VB described to date. DESIGN AND METHODS: Post hoc analysis of
      data acquired in the frame of a 36-months EP cohort study. A total of 265 EP
      patients, aged 18 to 35, treated at TIPP (Treatment and early Intervention in
      Psychosis Program), at the Department of Psychiatry in Lausanne, Switzerland,
      were included in the study. Logistic regression analyzes were performed as well
      as mediation analysis and interaction analysis RESULTS: Our data suggest that
      impulsivity is a predictor of VB when analyzed independently and as part of a
      multi-factorial model. Impulsivity continues to differentiate violent patients
      from non-violent ones at the end of the program. In addition, the relationship
      between impulsivity and VB is not mediated by substance abuse. Finally, the
      effect of impulsivity on the probability of VB is potentiated by the interaction
      of different levels of insight and positive symptoms. CONCLUSIONS: Early
      intervention strategies in psychotic disorders should include evaluation of
      impulsivity considering it is linked to increased risk of VB and may respond to
      treatment.

PMID- 29353179
TI  - Features of borderline personality disorder as a mediator of the relation between
      childhood traumatic experiences and psychosis-like experiences in patients with
      mood disorder.
AB  - BACKGROUND: Psychosis-like experiences (PEs) are common in patients with non
      psychotic disorders. Several factors predict reporting of PEs in mood disorders,
      including mood-associated cognitive biases, anxiety and features of borderline
      personality disorder (BPD). Childhood traumatic experiences (CEs), often reported
      by patients with BPD, are an important risk factor for mental disorders. We
      hypothesized that features of BPD may mediate the relationship between CEs and
      PEs. In this study, we investigated the relationships between self-reported PEs,
      CEs and features of BPD in patients with mood disorders. METHODS: As part of the
      Helsinki University Psychiatric Consortium study, McLean Screening Instrument
      (MSI), Community Assessment of Psychic Experiences (CAPE-42) and Trauma and
      Distress Scale (TADS) were filled in by patients with mood disorders (n = 282) in
      psychiatric care. Correlation coefficients between total scores of scales and
      their dimensions were estimated, multiple regression and mediation analyses were
      conducted. RESULTS: Total scores of MSI correlated strongly with scores of the
      CAPE-42 dimension "frequency of positive symptoms" (rho = 0.56; p <= 0.001) and
      moderately with scores of TADS (rho = 0.4; p <= 0.001). Total score of MSI and
      its dimension "cognitive symptoms", including identity disturbance,
      distrustfulness and dissociative symptoms, fully mediated the relation between
      TADS and CAPE-42. Each cognitive symptom showed a partial mediating role
      (dissociative symptoms 43% (CI = 25-74%); identity disturbance 40% (CI = 30-73%);
      distrustfulness 18% (CI = 12-50%)). CONCLUSIONS: Self-reported cognitive
      perceptual symptoms of BPD fully mediate, while affective, behavioural and
      interpersonal symptoms only partially mediate the relationships between CEs and
      PEs. Recognition of co-morbid features of BPD in patients with mood disorders
      reporting PEs is essential.

PMID- 29353180
TI  - Differential changes in the spinal segmental locomotor output in Hereditary
      Spastic Paraplegia.
AB  - OBJECTIVE: A comprehensive treatment of Hereditary Spastic Paraplegia (HSP)
      should consider the specific pathophysiological changes in the spinal cord. Here
      we reported a detailed characterization of the spinal motoneuronal output in HSP
      during locomotion. METHODS: We recorded kinematics and electromyographic (EMG)
      activity of 12 leg muscles in 29 patients with pure forms of HSP and compared
      them with 30 controls while walking at matched speeds. We assessed the spinal
      locomotor output by evaluating EMG patterns and by mapping them onto the
      rostrocaudal location of the spinal motoneuron pools. RESULTS: The activity
      profiles of muscles innervated from the sacral segments were significantly wider
      in patients. Similarly, spinal maps revealed a tendency for spreading the main
      loci of activation, involving initially the sacral segments and, at more severe
      stages, the lumbar segments. CONCLUSIONS: The degeneration of the corticospinal
      tract in HSP is associated with a widening of spinal locomotor output spreading
      from caudal to rostral segments. SIGNIFICANCE: The findings highlight
      pathophysiologically relevant differential changes in the spinal locomotor output
      in HSP related to the specific innervation of muscles in the spinal cord, and
      might be helpful for developing future therapeutic strategies and identifying
      physiological markers of the disease.

PMID- 29353181
TI  - Neurophysiological correlates of word processing deficits in isolated reading and
      isolated spelling disorders.
AB  - OBJECTIVE: In consistent orthographies, isolated reading disorders (iRD) and
      isolated spelling disorders (iSD) are nearly as common as combined reading
      spelling disorders (cRSD). However, the exact nature of the underlying word
      processing deficits in isolated versus combined literacy deficits are not well
      understood yet. METHODS: We applied a phonological lexical decision task
      (including words, pseudohomophones, legal and illegal pseudowords) during ERP
      recording to investigate the neurophysiological correlates of lexical and
      sublexical word-processing in children with iRD, iSD and cRSD compared to
      typically developing (TD) 9-year-olds. RESULTS: TD children showed enhanced early
      sensitivity (N170) for word material and for the violation of orthographic rules
      compared to the other groups. Lexical orthographic effects (higher LPC amplitude
      for words than for pseudohomophones) were the same in the TD and iRD groups,
      although processing took longer in children with iRD. In the iSD and cRSD groups,
      lexical orthographic effects were evident and stable over time only for correctly
      spelled words. CONCLUSIONS: Orthographic representations were intact in iRD
      children, but word processing took longer compared to TD. Children with spelling
      disorders had partly missing orthographic representations. SIGNIFICANCE: Our
      study is the first to specify the underlying neurophysiology of word processing
      deficits associated with isolated literacy deficits.

PMID- 29353182
TI  - Observations on muscle activity in REM sleep behavior disorder assessed with a
      semi-automated scoring algorithm.
AB  - OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is defined by
      dream enactment due to a failure of normal muscle atonia. Visual assessment of
      this muscle activity is time consuming and rater-dependent. METHODS: An EMG
      computer algorithm for scoring 'tonic', 'phasic' and 'any' submental muscle
      activity during REM sleep was evaluated compared with human visual ratings.
      Subsequently, 52 subjects were analyzed with the algorithm. Duration and maximal
      amplitude of muscle activity, and self-awareness of RBD symptoms were assessed.
      RESULTS: The computer algorithm showed high congruency with human ratings and all
      subjects with RBD were correctly identified by excess of submental muscle
      activity, when artifacts were removed before analysis. Subjects with RBD
      exhibited prolonged bouts of 'phasic' muscle activity with high amplitude. Self
      awareness of RBD symptoms correlated with amount of REM sleep without atonia.
      CONCLUSIONS: Our proposed algorithm was able to detect and rate REM sleep without
      atonia allowing identification of RBD. Increased duration and amplitude of muscle
      activity bouts were characteristics of RBD. Quantification of REM sleep without
      atonia represents a marker of RBD severity. SIGNIFICANCE: Our EMG computer
      algorithm can support a diagnosis of RBD while the quantification of altered
      muscle activity provides a measure of its severity.

PMID- 29353183
TI  - Automatic bad channel detection in intracranial electroencephalographic
      recordings using ensemble machine learning.
AB  - OBJECTIVE: Intracranial electroencephalographic (iEEG) recordings contain "bad
      channels", which show non-neuronal signals. Here, we developed a new method that
      automatically detects iEEG bad channels using machine learning of seven signal
      features. METHODS: The features quantified signals' variance, spatial-temporal
      correlation and nonlinear properties. Because the number of bad channels is
      usually much lower than the number of good channels, we implemented an ensemble
      bagging classifier known to be optimal in terms of stability and predictive
      accuracy for datasets with imbalanced class distributions. This method was
      applied on stereo-electroencephalographic (SEEG) signals recording during low
      frequency stimulations performed in 206 patients from 5 clinical centers.
      RESULTS: We found that the classification accuracy was extremely good: It
      increased with the number of subjects used to train the classifier and reached a
      plateau at 99.77% for 110 subjects. The classification performance was thus not
      impacted by the multicentric nature of data. CONCLUSIONS: The proposed method to
      automatically detect bad channels demonstrated convincing results and can be
      envisaged to be used on larger datasets for automatic quality control of iEEG
      data. SIGNIFICANCE: This is the first method proposed to classify bad channels in
      iEEG and should allow to improve the data selection when reviewing iEEG signals.

PMID- 29353184
TI  - Tumour-like giant nerves in entrapment neuropathies.

PMID- 29353185
TI  - Neurophysiologic characterization of periodic paralysis episode in a patient with
      Andersen-Tawil syndrome.

PMID- 29353186
TI  - Addictive behaviors, social and psychosocial factors, and electronic cigarette
      use among adolescents: a population-based study.
AB  - OBJECTIVES: The aim was to investigate associations between e-cigarette use and
      social and psychosocial factors and cigarette smoking, alcohol consumption, and
      narcotics use among adolescents attending 9th grade in primary school and 2nd
      grade in secondary school. STUDY DESIGN: Cross-sectional study. METHODS: The
      public health survey among adolescents in Scania in 2016 includes pupils in
      grades 9 and 2. The associations between e-cigarette use and lifestyle, social
      and psychosocial factors, and trust were investigated with logistic regressions.
      RESULTS: In 9th grade, 32% of male pupils and 27% of female pupils had ever used
      e-cigarettes, and in 2nd grade, 43% of males and 31% of females had ever used e
      cigarettes. E-cigarette use was significantly associated with current smoking,
      snus (a moist powder tobacco product originating in Sweden) use, water pipe use,
      intensive alcohol consumption, and narcotics and also with psychosocial
      conditions related to home and parents, peers, and school. CONCLUSIONS: The
      prevalence of ever e-cigarette use was high among adolescents attending both
      grades. E-cigarette use was most strongly associated with health-related
      lifestyles. It was also associated with psychosocial factors such as study
      difficulties, school stress, problems talking with parents, and generalized
      trust.

PMID- 29353188
TI  - Mechanism of anaerobic bio-reduction of azo dye assisted with lawsone-immobilized
      activated carbon.
AB  - Lawsone redox (LQ) mediator was covalently bound to granular activated carbon
      (GAC) by Fischer esterification. A high LQ adsorption capacity on GAC was
      achieved (~230 mg/g), and desorption studies showed strong chemical stability.
      Furthermore, kinetic experiments with solid-phase redox mediator (RM) and their
      controls (soluble RM, GAC and anaerobic sludge) were tested for decolorization of
      congo red dye at initial concentration of 175 mg/L. Benzidine, a by-product of
      complete congo red reduction, was also measured by HPLC analysis along the
      kinetic experiments. The highest percentage of decolorization after 24 h of
      incubation was achieved in cultures with soluble (77%) and immobilized (70%) LQ.
      In contrast, low decolorization efficiency was reached in anaerobic bio-reduction
      assays with unmodified GAC (47%) and anaerobic sludge (28%) after 24 h. Removal
      of congo red by adsorption onto LQ-GAC was negligible. The rate of benzidine
      production was slower than decolorization rate, suggesting that one azo bond of
      congo red is selectively broke and followed by a slower breaking of the second
      azo bond, consequently, appearance of benzidine in solution. These issues could
      be attributed to the steric rearrangement and the inhibitory effects of the
      produced aromatic amines in the biotransformation process.

PMID- 29353187
TI  - Medication use in a cohort of newly admitted nursing home residents (Ageing@NH)
      in relation to evolving physical and mental health.
AB  - BACKGROUND: Medication use is high among nursing home (NH) residents, but there
      is a lack of longitudinal studies, determining medication use at admission and
      its evolution over time. AIM: Describing the evolution of the medication use two
      years after entering a NH, compared to the baseline observations and exploring
      the relation to the physical and mental health. METHODS: Data from the
      observational prospective Ageing@NH study, based on an inception cohort of newly
      admitted residents at NHs (65+) was used, selecting those consenting and with
      medication chart available. Information about socio-demographic, functional and
      mental characteristics, as well as medication use, was collected at baseline,
      year 1 and year 2. RESULTS: Medication chart was available for n = 741 at
      baseline (mean age 83.8, 66% female), and for n = 342 residents in year 2. The
      mean number of total medications increased from 8.9 to 10.1 (p-value < 0.001).
      Polypharmacy was high, with an increase in extreme polypharmacy from 23% to 32%.
      The biggest increase was noted in the respiratory (from 17% to 27%) and
      alimentary medications (from 80% to 87%). Cardiovascular medication use in year
      2, was lower in those with stable high dependency (77%) and those evolving from
      low to high dependency (79%), than those with stable low dependency (89%) (p <
      0.025). For residents with or evolving to dementia symptoms, decline in most
      medication groups was observed, especially in pain and sleeping medications,
      while antipsychotics use increased. CONCLUSION: Although medication use was high,
      signs of deprescribing were noted when the physical and mental health of the
      residents declined.

PMID- 29353189
TI  - Synthesis of cross-linked protein-metal hybrid nanoflowers and its application in
      repeated batch decolorization of synthetic dyes.
AB  - Herein, we report the preparation of a cross-linked protein-metal hybrid
      nanoflower (NF) system for laccase immobilization. The immobilized laccase showed
      effective encapsulation yield and activity recovery of 78.1% and 204%,
      respectively. The catalytic efficiency (kcatVmax-1) of cross-linked NF (CL-NF)
      was 2.2-fold more than that of free laccase. The CL-NF also exhibited
      significantly higher stability towards pH and temperature changes. It exhibited
      excellent storage stability and tolerance towards solvents and inhibitors as
      compared with the free enzyme. After 10 cycles of reuses, the NF and CL-NF
      laccase showed 41.2% and 92.3% residual activity, respectively. The CL-NF showed
      high oxidation potential, 265% that of the free enzyme, towards phenolic
      compounds. The CL-NF laccase retained the residual decolorization efficiency of
      up to 84.6% for synthetic dyes under repeated batch conditions of 10 cycles.
      These results suggested that the preparation of CL-NF is an effective approach to
      enhance the enzymatic properties and has great potential in many industrial
      applications.

PMID- 29353190
TI  - Characterization of acrylamide-induced oxidative stress and cardiovascular
      toxicity in zebrafish embryos.
AB  - Acrylamide (AA) is a high production volume chemical in industrial applications
      and widely found in baked or fried carbohydrate-rich foods. In this study, we
      unravelled that AA induced developmental toxicity associated with oxidative
      stress status and disordered lipid distribution in heart region of developing
      zebrafish. Treatment with AA caused a deficient cardiovascular system with
      significant heart malformation and dysfunction. We also found that AA could
      reduce the number of cardiomyocytes through the reduced capacity of cardiomyocyte
      proliferation rather than cell apoptosis. The cardiac looping and ballooning
      appeared abnormal though cardiac chamber-specific identity in the differentiated
      myocardium was maintained well after AA treatment through MF20/S46
      immunofluorescence assay. Furthermore, treatment with AA disturbed the
      differentiation of atrioventricular canal, which was demonstrated by the
      disordered expressions of the atrioventricular boundary markers bmp4, tbx2b and
      notch1b and further confirmed by the ectopic expressions of the cardiac valve
      precursor markers has2, klf2a and nfatc1 through whole-mount in situ
      hybridization. Thus, our studies provide the evidence of cardiac developmental
      toxicity of AA in the cardiovascular system, and also raised health concern about
      the harm of trans-placental exposure to high level of AA for foetuses and the
      risk of high exposure to AA for the pregnant women.

PMID- 29353192
TI  - Monte Carlo calculations of the cellular S-values for alpha-particle-emitting
      radionuclides incorporated into the nuclei of cancer cells of the MDA-MB231, MCF7
      and PC3 lines.
AB  - S-values (dose per unit of cumulated activity) for alpha particle-emitting
      radionuclides and monoenergetic alpha sources placed in the nuclei of three
      cancer cell models (MCF7, MDA-MB231 breast cancer cells and PC3 prostate cancer
      cells) were obtained by Monte Carlo simulation. The MCNPX code was used to
      calculate the fraction of energy deposited in the subcellular compartments due to
      the alpha sources in order to obtain the S-values. A comparison with
      internationally accepted S-values reported by the MIRD Cellular Committee for
      alpha sources in three sizes of spherical cells was also performed leading to an
      agreement within 4% when an alpha extended source uniformly distributed in the
      nucleus is simulated. This result allowed to apply the Monte Carlo Methodology to
      evaluate S-values for alpha particles in cancer cells. The calculation of S
      values for nucleus, cytoplasm and membrane of cancer cells considering their
      particular geometry, distribution of the radionuclide source and chemical
      composition by means of Monte Carlo simulation provides a good approach for
      dosimetry assessment of alpha emitters inside cancer cells. Results from this
      work provide information and tools that may help researchers in the selection of
      appropriate radiopharmaceuticals in alpha-targeted cancer therapy and improve its
      dosimetry evaluation.

PMID- 29353191
TI  - Kinetic and equilibrium modelling of MTBE (methyl tert-butyl ether) adsorption on
      ZSM-5 zeolite: Batch and column studies.
AB  - The intensive use of methyl tert-butyl ether (MTBE) as a gasoline additive has
      resulted in serious environmental problems due to its high solubility, volatility
      and recalcitrance. The feasibility of permeable reactive barriers (PRBs) with ZSM
      5 type zeolite as a reactive medium was explored for MTBE contaminated
      groundwater remediation. Batch adsorption studies showed that the MTBE adsorption
      onto ZSM-5 follows the Langmuir model and obeys the pseudo-second-order model
      with an adsorption capacity of 53.55 mg g-1. The adsorption process reached
      equilibrium within 24 h, and MTBE was barely desorbed with initial MTBE
      concentration of 300 mg L-1. The mass transfer process is found to be primarily
      controlled by pore diffusion for MTBE concentrations from 100 to 600 mg L-1. pH
      has little effect on the maximum adsorption capacity in the pH range of 2-10,
      while the presence of nickel reduces the capacity with Ni concentrations of 2.5
      25 mg L-1. In fixed-bed column tests, the Dose-Response model fits the
      breakthrough curve well, showing a saturation time of ~320 min and a removal
      capacity of ~18.71 mg g-1 under the conditions of this study. Therefore, ZSM-5 is
      an extremely effective adsorbent for MTBE removal and has a huge potential to be
      used as a reactive medium in PRBs.

PMID- 29353193
TI  - Automated radiosynthesis of Al[18F]PSMA-11 for large scale routine use.
AB  - OBJECTIVES: We report a reproducible automated radiosynthesis for large scale
      batch production of clinical grade Al[18F]PSMA-11. METHODS: A SynthraFCHOL module
      was optimized to synthesize Al[18F]PSMA-11 by Al[18F]-chelation. Results
      Al[18F]PSMA-11 was synthesized within 35min in a yield of 21 +/- 3% (24.0 +/-
      6.0GBq) and a radiochemical purity > 95%. Batches were stable for 4h and conform
      the European Pharmacopeia guidelines. CONCLUSIONS: The automated synthesis of
      Al[18F]PSMA-11 allows for large scale production and distribution of Al[18F]PSMA
      11.

PMID- 29353194
TI  - Investigation of the favorable etching time of CN-85 nuclear track detector.
AB  - The favorable etching time of alpha tracks registered in CN-85 solid-state
      nuclear track detector was explored by chemical etching heated by three different
      techniques: the classical water bath, unconventional microwave, and ultrasound
      techniques. The parameters that affect the etching of the tracks, namely the rate
      of bulk etching (VB), the rate of track etching (VT), the ratio of track etching
      (V), the critical angle (thetac), and the registration efficiency (eta), were
      determined. The favorable etching times to develop the highest number of
      registered tracks in CN-85 irradiated with alpha particles emanated from a 241Am
      source was found to be 30, 10, and 20min for water bath, microwave, and
      ultrasound heating techniques, respectively. The obtained results showed the
      track density possesses the highest value when the detector was etched by
      different heating techniques: ultrasound, water bath, and microwave heating
      technique respectively. As well as, the etching time was faster when the etching
      was done by microwave, ultrasound, and water bath. Moreover the results might
      also showed that the etching parameters (except OC) are maximum with using
      microwave, ultrasound, and microwave, respectively.

PMID- 29353195
TI  - Neutron field characterization at the independent spent fuel storage installation
      of the Trillo nuclear power plant.
AB  - Neutron fields inside and outside the independent spent fuel storage installation
      of Trillo Nuclear Power Plant are characterized exhaustively in terms of neutron
      spectra and ambient dose equivalent, measured by Bonner sphere system and LB6411
      monitor. Measurements are consistent with storage casks and building shield
      characteristics, and also with casks distribution inside the building. Outer
      values at least five times lower than dose limit for free access area are found.
      Measurements with LB6411 and spectrometer are consistent with each other.

PMID- 29353196
TI  - High adsorption of methylene blue by salicylic acid-methanol modified steel
      converter slag and evaluation of its mechanism.
AB  - A novel adsorbent based on steel converter slag (SCS), useful for adsorbing
      cationic pollutants from water was prepared by a simple method. The
      characterization showed that salicylic acid-methanol (SAM) modification
      selectively removed calcium silicate minerals from the surface of SCS and lead to
      a prominent increase in the specific surface areas. The maximum adsorption
      capacity of SAM-modified SCS for methylene blue (MB) at initial pH of 7.0 and
      temperature of 293 K was 41.62 mg/g, which is 35.2-times higher than that of SCS
      (1.15 mg/g). Adsorption kinetics and isotherms of MB on the SAM-modified SCS can
      be satisfactorily fitted by pseudo-second order kinetic and Langmuir model,
      respectively, which suggest that single-layer chemical adsorption was mainly
      responsible for MB removal. Further studies showed that pH value and ionic
      strength of wastewater have minimal effects on the adsorption capacity of SAM
      modified SCS. A small decrease (<10%) was found in the adsorption capacity of SAM
      modified SCS after five cycles. These findings indicate that SAM-modified SCS is
      a promising adsorbent for the efficient removal of MB from aqueous solution due
      to its low cost, good thermal stability, excellent adsorption performance and
      simple separation.

PMID- 29353197
TI  - Bioanalytical assessment of adaptive stress responses in drinking water: A
      predictive tool to differentiate between micropollutants and disinfection by
      products.
AB  - Drinking water can contain low levels of micropollutants, as well as disinfection
      by-products (DBPs) that form from the reaction of disinfectants with organic and
      inorganic matter in water. Due to the complex mixture of trace chemicals in
      drinking water, targeted chemical analysis alone is not sufficient for
      monitoring. The current study aimed to apply in vitro bioassays indicative of
      adaptive stress responses to monitor the toxicological profiles and the formation
      of DBPs in three drinking water distribution systems in France. Bioanalysis was
      complemented with chemical analysis of forty DBPs. All water samples were active
      in the oxidative stress response assay, but only after considerable sample
      enrichment. As both micropollutants in source water and DBPs formed during
      treatment can contribute to the effect, the bioanalytical equivalent
      concentration (BEQ) approach was applied for the first time to determine the
      contribution of DBPs, with DBPs found to contribute between 17 and 58% of the
      oxidative stress response. Further, the BEQ approach was also used to assess the
      contribution of volatile DBPs to the observed effect, with detected volatile DBPs
      found to have only a minor contribution as compared to the measured effects of
      the non-volatile chemicals enriched by solid-phase extraction. The observed
      effects in the distribution systems were below any level of concern, quantifiable
      only at high enrichment and not different from bottled mineral water. Integrating
      bioanalytical tools and the BEQ mixture model for monitoring drinking water
      quality is an additional assurance that chemical monitoring is not overlooking
      any unknown chemicals or transformation products and can help to ensure
      chemically safe drinking water.

PMID- 29353198
TI  - A tiered approach to assess effects of diclofenac on the brown mussel Perna
      perna: A contribution to characterize the hazard.
AB  - Pharmaceutical discharges into the aquatic ecosystem are of environmental concern
      and sewage treatment plants (STPs) have been pointed out as the major source of
      these compounds to coastal zones, where oceanic disposal of sewage occurs through
      submarine outfalls. Diclofenac (DCF) is one of the most frequently detected
      pharmaceuticals in water, but little is known about the effects on marine
      organisms. In this study, we employed a tiered approach involving the
      determination of environmental concentrations of DCF in marine water and the
      adverse biological effects for fertilization, embryo-larval development and
      biomarker responses of the mussel Perna perna. Results indicate that effects in
      fertilization rate and embryo-larval development were found in the order of mg.L
      1. However, low concentrations of DCF (ng.L-1) significantly decreased the
      lysosomal membrane stability and COX activity, as well as triggered DNA damage,
      oxidative stress and changes in antioxidant defenses. Our results point to an
      environmental hazard at coastal ecosystems and suggest the need for improvements
      in the treatment of domestic wastewater aiming to reduce DCF concentrations, as
      well as regulation on current environmental legislation and monitoring of aquatic
      ecosystems.

PMID- 29353199
TI  - Applicability of Kd for modelling dissolved 137Cs concentrations in Fukushima
      river water: Case study of the upstream Ota River.
AB  - A study is presented on the applicability of the distribution coefficient (Kd)
      absorption/desorption model to simulate dissolved 137Cs concentrations in
      Fukushima river water. The upstream Ota River basin was simulated using GEneral
      purpose Terrestrial Fluid-flow Simulator (GETFLOWS) for the period 1 January 2014
      to 31 December 2015. Good agreement was obtained between the simulations and
      observations on water and suspended sediment fluxes, and on particulate bound
      137Cs concentrations under both base and high flow conditions. By contrast the
      measured concentrations of dissolved 137Cs in the river water were much harder to
      reproduce with the simulations. By tuning the Kd values for large particles, it
      was possible to reproduce the mean dissolved 137Cs concentrations during base
      flow periods (observation: 0.32 Bq/L, simulation: 0.36 Bq/L). However neither the
      seasonal variability in the base flow dissolved 137Cs concentrations (0.14-0.53
      Bq/L), nor the peaks in concentration that occurred during storms (0.18-0.88
      Bq/L, mean: 0.55 Bq/L), could be reproduced with realistic simulation parameters.
      These discrepancies may be explained by microbial action and leaching from
      organic matter in forest litter providing an additional input of dissolved 137Cs
      to rivers, particularly over summer, and limitations of the Kd
      absorption/desorption model. It is recommended that future studies investigate
      these issues in order to improve simulations of dissolved 137Cs concentrations in
      Fukushima rivers.

PMID- 29353200
TI  - Monitoring of soil radon by SSNTD in Eastern India in search of possible
      earthquake precursor.
AB  - The present paper deals with monitoring soil radon-222 concentration at two
      different locations, designated Site A and Site B, 200 m apart at Jadavpur
      University campus, Kolkata, India, with a view to find possible precursors for
      the earthquakes that occurred within a few hundred kilometers from the monitoring
      site. The solid state nuclear track detector CR-39 has been used for detection of
      radon gas coming out from soil. Radon-222 time series at both locations during
      the period August 2012-December 2013 have been analysed. Distinct anomalies in
      the soil radon time series have been observed for seven earthquakes of magnitude
      greater than 4.0 M that occurred during this time. Of these, radon anomalies for
      two earthquakes have been observed at both locations A and B. Absence of
      anomalies for some other earthquakes has been discussed, and the observations
      have been compared with some earthquake precursor models.

PMID- 29353201
TI  - miR-204 inhibits angiogenesis and promotes sensitivity to cetuximab in head and
      neck squamous cell carcinoma cells by blocking JAK2-STAT3 signaling.
AB  - This study aims to investigate the roles of miR-204 in tumor angiogenesis of head
      and neck squamous cell carcinoma (HNSCC). Here, we found that miR-204 level was
      reduced in HNSCC tissues relative to that in normal adjacent tissues.
      Overexpression of miR-204 promoted tumor angiogenesis in HNSCC cells.
      Mechanistically, JAK2 was identified as a direct target of miR-204, and miR-204
      overexpression blocked JAK2/STAT3 pathway. Moreover, overexpression of JAK2
      attenuated the inhibition of miR-204 on tumor angiogenesis of HNSCC. Furthermore,
      overexpression of miR-204 enhanced sensitivity of cetuximab in HNSCC cells, this
      effect was attenuated by JAK2 overexpression too. Importantly, JAK2 expression
      was negatively correlated with miR-204 level in HNSCC tissues. Therefore, miR-204
      acts as a tumor suppressor by blocking JAK2/STAT3 pathway in HNSCC cells.

PMID- 29353202
TI  - Validation of a traditional preparation against multi-drug resistant Salmonella
      Typhi and its protective efficacy in S. Typhimurium infected mice.
AB  - Shorea robusta Gaertn has been used for skin and intestinal ailments in Indian
      Traditional medicine; while two tribal communities used its tender leaves in
      'Meyadi-bukhar' or long-term fever. This prompted us to validate the aqueous and
      methanol extracts of Shorea robusta tender leaves against wild- and multidrug
      resistant clinical isolates of Salmonella enterica Serovar Typhi (S. Typhi), the
      causative agent of typhoid fever. The antibacterial activity, minimum inhibitory
      concentration (MIC), minimum bactericidal concentration (MBC) and growth
      inhibition were determined using disc diffusion, agar-and-broth dilution, dose-
      and time-response assays, along with the safety and protective efficacy in Balb/C
      mice, infected with S. Typhimurium. The MIC of the extract was 256-450 MUg/ml
      against S. Typhi isolates, and 700 MUg/ml for mouse virulent S. Typhimurium,
      while MBC was <=512-1024 MUg/ml. The growth curve revealed that the extract was
      bactericidal at 4-6 h of exposure. Toxicity study showed that the extract was
      safe up to 3000 mg/kg (p.o.). Moreover, it significantly (p > 0.01) protect the
      challenged (1.4 * 108 cfu/ml) mice at 93.75 (i.p.) and 300 mg/kg (p.o.) dose,
      compared to the infection control (distilled water treatment group).
      Collectively, our results confirmed the antibacterial potential of the test
      extracts against MDR-isolates of S. Typhi.

PMID- 29353203
TI  - The water extract of tutsan (Hypericum androsaemum L.) red berries exerts
      antidepressive-like effects and in vivo antioxidant activity in a mouse model of
      post-stroke depression.
AB  - Hypericum androsaemum L., commonly known as 'tutsan' or 'shrubby St. John's
      Wort', is a member of the Hypericum genus found growing spontaneously in the
      Mediterranean area and is cultivated extensively as an ornamental plant due to
      the showy color variation in its fresh berry-like capsules, which turn from red
      to shiny black as they ripen. Tutsan has also been used in Portuguese and Spanish
      folk medicine to treat depression. In this study, we assessed the beneficial role
      of the water extract of H. androsaemum red berries (WE) in an experimental animal
      model of post-stroke depression. WE was obtained by decoction of H. androsaemum
      red berries, and its content of ten bioactive compounds was determined through
      HPLC-DAD analysis. Behavioral tests were carried out using a mouse model of post
      stroke depression to examine the antidepressive-like activity of WE at two doses
      (15 and 30 mg/kg bw). In addition, the in vivo antioxidant activity in the mouse
      brain was evaluated by measuring CAT, GSH, and SOD activity and TBARS levels. WE
      contained significant amounts of shikimic acid (110.0 g/kg), chlorogenic acid
      (56.9 g/kg), catechin (5.8 g/kg) and hyperoside (2.7 g/kg). Overall, the highest
      dosage of WE was found to significantly reduce the symptoms of depression,
      restoring normal behaviour and reducing levels of oxidative stress by increasing
      endogenous antioxidant defenses. The protective effects of WE in post-stroke
      depression in a mouse model were demonstrated in vivo for the first time, and
      correlated with the antioxidant capacity of its bioactive constituents.

PMID- 29353204
TI  - miR-152 inhibits proliferation of human endometrial cancer cells via inducing
      G2/M phase arrest by suppressing CDC25B expression.
AB  - microRNA-152 (miR-152) is a tumor suppressor that is down-regulated in many
      cancers including endometrial cancer (EC). However, the underlying mechanism of
      action of miR-152 in EC is unclear. The aim of the present study was to evaluate
      the role of miR-152 on proliferation of human endometrial cancer cells. Herein,
      we found that miR-152 overexpression and CDC25B knockdown inhibited proliferative
      ability and induced G2/M phase arrest in KLE and HEC-1B cells. CDC25B was a
      target of miR-152. In addition, CDC25B overexpression rescued miR-152-induced
      proliferation inhibition and G2/M phase arrest in human endometrial cancer cells.
      The results indicated that miR-152 was a tumor suppressor in EC that inhibited
      proliferation of human endometrial cancer cells via inducing G2/M phase arrest by
      suppressing CDC25B expression.

PMID- 29353205
TI  - WISP3 prevents fibroblast-myofibroblast transdifferentiation in NRK-49F cells.
AB  - CCN family, a group of six extracellular matrix-associated proteins, plays an
      important role in fibrosis. WISP3 has addressed as a pro-fibrotic molecule in the
      development of human lung fibrosis. However, whether WISP3 involved in the
      activation and proliferation of renal fibroblast, and ultimately inhibited
      fibroblast-myofibroblast transdifferentiation remained unknown. Herein, we found
      that down-regulated WISP3 was involved in the fibrogenesis of rat renal NRK-49F
      cells induced by transforming growth (TGF-beta1), which was further confirmed in
      a rat renal fibrosis induced by unilateral ureteral obstruction (UUO). In the
      present study, we aimed to investigate the roles of WISP3 in NRK-49F fibroblast
      myofibroblast transdifferentiation, and the underlying mechanism. Results showed
      that after TGF-beta1 treatment, significant increased cell proliferation, and up
      regulated expressions of TGF-beta1, connective tissue growth factor (CTGF), alpha
      smooth muscle actin (alpha-SMA), vimentin, as well as increased concentrations of
      collagen types I (COL I), collagen types III (COL III) and hydroxyproline in cell
      culture supernatant were observed, demonstrating a successful establishment of
      fibroblast-myofibroblast transdifferentiation of NRK-49F cells. Besides, siRNA
      WISP3 remarkably promoted the fibrogenesis of NRK-49F cells with or without TGF
      beta1 treatment, and increased mRNA levels of Axin, demonstrating that activating
      WNT signaling pathway was the underlying mechanism. However, lentivirus-mediated
      WISP3 overexpression exerted an opposite effect, protecting NRK-49F cells from
      transdifferentiation, and decreasing mRNA levels of Axin. In conclusion, the
      WISP3 played an anti-fibrotic role in NRK-49F cells, and WNT signaling pathway
      was the potential mechanism. WISP3 was an anti-fibrotic factor in fibroblast
      myofibroblast transdifferentiation, and may be used as a possible target for
      prevention and treatment of human renal fibrosis.

PMID- 29353206
TI  - Dihydroartemisinin ameliorates sepsis-induced hyperpermeability of glomerular
      endothelium via up-regulation of occludin expression.
AB  - Sepsis, the systemic inflammatory responses after infection, remains a serious
      cause of morbidity and mortality in critically ill patients. The anti-malarial
      agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this
      study, we examined the effects of DHA on sepsis-induced acute kidney injury (AKI)
      and explored the mechanism underlying its mode of action in AKI. In a
      lipopolysaccharide (LPS)-induced mouse model, we observed that DHA treatment
      ameliorated glomerular injury, and relieved elevation of the urine albumin to
      creatinine ratio (UACR) and serum creatinine. At a concentration of 25 MUM, DHA
      had no effect on overall cellular viability or apoptosis in assays with human
      renal glomerular endothelial cells (HRGECs), but significantly inhibited the
      tumor necrosis factor-alpha (TNF-alpha)-induced hyperpermeability of HRGEC
      monolayers. We found that TNF-alpha decreases the expression of the junctional
      protein occludin in HRGECs, which is reversed by DHA. Taken together, our results
      demonstrate that DHA decreases permeability of the glomerular endothelium by
      maintenance of occludin expression. This suggests DHA may have therapeutic
      utility in sepsis-induced AKI.

PMID- 29353207
TI  - Geraniin promotes osteoblast proliferation and differentiation via the activation
      of Wnt/beta-catenin pathway.
AB  - Geraniin is an ellagitannin isolated from Phyllanthus amarus and has a wide range
      of bioactivities. Our previous study demonstrated that geraniin could alleviate
      osteoporosis by accelerating bone formation, but the mechanism remains unclear.
      This study aimed to elucidate the molecular mechanisms by which geraniin promotes
      osteoblast proliferation and differentiation in vitro. Primary rat bone marrow
      derived mesenchymal stem cells were separated and divided into sham operated
      (Sham) group, Sham treated with geraniin (Sham + GE) group, ovariectomized (OVX)
      group, OVX treated with geraniin (OVX + GE) group, OVX treated with osteogenic
      medium (OVX + OM) group, OVX treated with Wnt inhibitor (OVX + WI) group, and OVX
      treated with Wnt inhibitor and geraniin (OVX + W I + GE) group. Following
      bilateral ovariectomy, the expression of beta-catenin, frizzled2, LRP6, TCF4,
      LEF1, c-myc, cyclin D1, Runx2 and osterix significantly reduced, while the
      expression of axin2 significantly increased (P < 0.05). Geraniin enhanced the
      expression of beta-catenin, frizzled2, LRP6, TCF4, LEF1, c-myc, cyclin D1, Runx2
      and osterix, while inhibited the expression of axin2 (P < 0.05). Wnt inhibitor
      significantly weakened geraniin-induced Wnt/beta-catenin activation (P < 0.05).
      In conclusion, geraniin enhances the activation of Wnt/beta-catenin pathway,
      which may explain how it promotes osteoblast proliferation and differentiation.

PMID- 29353208
TI  - Natural products berberine and curcumin exhibited better ameliorative effects on
      rats with non-alcohol fatty liver disease than lovastatin.
AB  - Studies have shown that satins and herbal products have potential to treat non
      alcohol fatty liver disease (NAFLD) in clinic. However, no study has compared
      their effects, and their mechanisms remain unresolved. Here, we choose lovastatin
      and two herbal products including berberine and curcumin to compare their effects
      in treating NAFLD. NAFLD model was established by high fat food, and rats were
      administrated with lovastatin, berberine, curcumin, berberine + curcumin at the
      dosage of 100, 100, 100, 50 + 50 mg/kg bw, respectively. The body weight,
      visceral fat gain, histological inspection and serum parameters were studied to
      exam the curative effects. In addition, mediators including SREBP-1c, caveolin-1,
      pERK, NF-kappaB, TNF-alpha, and pJNK were studied. Results showed that berberine
      + curcumin group exhibited lower body and fat weigh compared with lovastatin
      group. Biochemical assays showed that LDL-c, ALT, AST, ALP, MDA, LSP level were
      lower in berberine + curcumin group compared with lovastatin group. Lower
      expression of SREBP-1c, pERK, TNF-alpha, and pJNK were also observed in berberine
      + curcumin group. We conclude that combination of curcumin and berberine
      exhibited better ameliorative effects in treating NAFLD than lovastatin, and this
      enhanced effect is associated with oxidative stress, hepatic inflammation and
      lipid metabolism.

PMID- 29353209
TI  - MiR-182 promotes prostate cancer progression through activating Wnt/beta-catenin
      signal pathway.
AB  - Although prostate cancer can be surgical excised and effectively treated by
      androgen-deprivation therapy, radiotherapy, or chemotherapy, management of
      patients with advanced or drug-resistance prostate cancer stills remains a big
      trouble. Accumulated evidence indicated that miR-182 and Wnt/beta-catenin
      function as tumor oncogene in the progression of a variety of tumors. However,
      little is known about how miR-182 regulates beta-catenin signal molecular and
      impacts on the tumorigenesis of human prostate cancer. In this study, employing
      the analyses of qRT-PCR, we found that prostate cancer tissues expressed much
      more miR-182 than non-cancer tissues did. In vitro studies revealed that
      overexpression of miR-182 promoted cell proliferation, colony formation,
      migration, invasion and inhibited cell apoptosis; in vivo results demonstrated
      that silencing of miR-182 mediated by inhibitor dramatically reduced prostate
      cancer xenograft tumor growth. Importantly, through western blotting analysis, we
      identified that miR-182 dramatically activated Wnt/beta-catenin pathway by
      targeting multiple negative regulators of Wnt/beta-catenin signaling, including
      GSK-3beta, APC, CK1 and Axin. Besides, we observed the elevated levels of c-myc
      and Cyclin D1 when PC-3 and LNCap cells were up-regulated miR-182. Our findings
      indicate that miR-182 acts as one of oncogenic factor in the progression of
      prostate cancer by recruiting a mechanism of aberrant activation of Wnt/beta
      catenin signaling.

PMID- 29353210
TI  - VPg unlinkase/TDP2 in cardiovirus infected cells: Re-localization and proteolytic
      cleavage.
AB  - Cardioviruses cause diseases in many animals including, in rare cases, humans.
      Although they share common features with all picornaviruses, cardioviruses have
      unique properties that distinguish them from other family members, including
      enteroviruses. One feature shared by all picornaviruses is the covalent
      attachment of VPg to the 5' end of genomic RNA via a phosphotyrosyl linkage. For
      enteroviruses, this linkage is cleaved by a host cell protein, TDP2. Since TDP2
      is divergently required during enterovirus infections, we determined if TDP2 is
      necessary during infection by the prototype cardiovirus, EMCV. We found that EMCV
      yields are reduced in the absence of TDP2. We observed a decrease in viral
      protein accumulation and viral RNA replication in the absence of TDP2. In
      contrast to enterovirus infections, we found that TDP2 is modified at peak times
      of EMCV infection. This finding suggests a unique mechanism for cardioviruses to
      regulate TDP2 activity during infection.

PMID- 29353212
TI  - Pregnant women with depressive and anxiety symptoms read, talk, and sing less to
      their fetuses.

PMID- 29353211
TI  - Examining a transdiagnostic measure of repetitive thinking in depressed, formerly
      depressed and never-depressed individuals.
AB  - BACKGROUND: Evidence that repetitive negative thinking (RNT) is a shared feature
      of a number of disorders has prompted the need for transdiagnostic self-report
      instruments; that is, measures of RNT that can be administered to individuals
      irrespective of their diagnosis. The Repetitive Thinking Questionnaire (RTQ;
      McEvoy et al., 2010) was developed to meet this need, and its psychometric
      properties and capacity to predict psychopathology have been tested in
      undergraduate and clinically anxious samples. METHODS: We administered the RTQ to
      currently depressed (n = 29), formerly depressed (n = 61) and never-depressed (n
      = 93) community participants. RESULTS: The RTQ demonstrated good psychometric
      properties, with excellent internal consistency for the RNT subscale (alpha=.93)
      and good convergent validity with measures of negative affect and psychopathology
      symptoms (rs= .47-.61). In addition, and in accord with our predictions,
      currently depressed and recovered depressed participants reported more RNT than
      never-depressed participants, but currently and recovered depressed participants
      did not differ. In addition, RNT scores explained additional variance in
      depression and anxiety symptoms, after controlling for gender, age, neuroticism,
      state negative affect, and intolerance of uncertainty. LIMITATIONS: Our sample
      was drawn from the community but participants were not treatment-seeking, and we
      employed a cross-sectional design. DISCUSSION: Taken together with previous
      experimental and longitudinal studies, our results support the utility of
      addressing RNT in the treatment and prevention of relapse in depression.
      Moreover, these data confirm the utility of the RTQ as a brief, transdiagnostic
      self-report measure of RNT.

PMID- 29353213
TI  - Multiple cortical thickness sub-networks and cognitive impairments in first
      episode, drug naive patients with late life depression: A graph theory analysis.
AB  - BACKGROUND: Coordinated and pattern-wise changes in large scale gray matter
      structural networks reflect neural circuitry dysfunction in late life depression
      (LLD), which in turn is associated with emotional dysregulation and cognitive
      impairments. However, due to methodological limitations, there have been few
      attempts made to identify individual-level structural network properties or sub
      networks that are involved in important brain functions in LLD. METHODS: In this
      study, we sought to construct individual-level gray matter structural networks
      using average cortical thicknesses of several brain areas to investigate the
      characteristics of the gray matter structural networks in normal controls and LLD
      patients. Additionally, we investigated the structural sub-networks correlated
      with several clinical measurements including cognitive impairment and depression
      severity. RESULTS: We observed that small worldness, clustering coefficients,
      global and local efficiency, and hub structures in the brains of LLD patients
      were significantly different from healthy controls. We further found that a sub
      network including the anterior cingulate, dorsolateral prefrontal cortex and
      superior prefrontal cortex is significantly associated with attention control and
      executive function. The severity of depression was associated with the sub
      networks comprising the salience network, including the anterior cingulate and
      insula. LIMITATIONS: We investigated cortico-cortical connectivity, but omitted
      the subcortical structures such as the striatum and thalamus. CONCLUSION: We
      report differences in patterns between several clinical measurements and sub
      networks from large-scale and individual-level cortical thickness networks in
      LLD.

PMID- 29353214
TI  - Effects of poor sleep quality on brain functional connectivity revealed by
      wavelet-based coherence analysis using NIRS methods in elderly subjects.
AB  - OBJECTIVE: Poor sleep quality, which is typically related to impairments in
      cognitive control, is pervasive among the elderly. However, the brain function
      mechanisms underlying the association between sleep and elderly behavior remain
      elusive. This study aims to assess the effects of poor sleep quality on low
      frequency neural oscillations based on the wavelet phase coherence (WPCO) and
      wavelet amplitude (WA) of oxyhemoglobin concentration changes (Delta [HbO2])
      measured through near-infrared spectroscopy (NIRS) method. METHODS: Subjective
      sleep quality was measured through the Pittsburgh Sleep Quality Index (PSQI).
      Continuously recorded NIRS signals from the prefrontal cortex, sensorimotor
      cortical, and occipital lobes of 15 poor-sleep-quality elderly subjects (PSQ
      group) as well as 14 healthy elderly subjects (control group) in the resting and
      task states. The WPCO and WA values were calculated in low frequency (0.01-0.08
      Hz). Pearson correlation analysis was used to assess the respective degrees of
      correlation between the WPCO of bilateral prefrontal lobes, WA of left prefrontal
      cortex (LPFC), WA of right prefrontal cortex (RPFC), F1 scores, and PSQI scores,
      respectively. RESULTS: The WPCO values were significantly lower in the PSQ group
      than in the control group (p < 0.05). Compared with the control group, the WA was
      significantly higher in the PSQ group and was also significantly higher in the
      resting state than in the task state. The F1 scores were significantly lower in
      the PSQ group when performing 1-back task. In the PSQ group, the correlation
      analysis showed the negative correlation between the PSQI scores and WPCO values.
      The WA values of LPFC and RFFC exhibited positive correlations with the PSQI
      scores. CONCLUSIONS: Collectively, these results suggest that poor sleep reduces
      phase synchronization, which may contribute to the diminished cognitive functions
      among the sample population.

PMID- 29353215
TI  - Sparks fly between ascorbic acid and iron-based nanozymes: A study on Prussian
      blue nanoparticles.
AB  - Herein we reported Prussian blue nanoparticles (PBNPs) possess ascorbic acid
      oxidase (AAO)- and ascorbic acid peroxidase (APOD)-like activities, which
      suppressed the formation of harmful H2O2 and finally inhibited the anti-cancer
      efficiency of ascorbic acid (AA). This newly revealed correlation between iron
      and AA could provide new insight for the studies of nanozymes and free radical
      biology.

PMID- 29353216
TI  - An efficient swarm intelligence approach to feature selection based on invasive
      weed optimization: Application to multivariate calibration and classification
      using spectroscopic data.
AB  - Variable selection plays a key role in classification and multivariate
      calibration. Variable selection methods are aimed at choosing a set of variables,
      from a large pool of available predictors, relevant to the analyte concentrations
      estimation, or to achieve better classification results. Many variable selection
      techniques have now been introduced among which, those which are based on the
      methodologies of swarm intelligence optimization have been more respected during
      a few last decades since they are mainly inspired by nature. In this work, a
      simple and new variable selection algorithm is proposed according to the invasive
      weed optimization (IWO) concept. IWO is considered a bio-inspired metaheuristic
      mimicking the weeds ecological behavior in colonizing as well as finding an
      appropriate place for growth and reproduction; it has been shown to be very
      adaptive and powerful to environmental changes. In this paper, the first
      application of IWO, as a very simple and powerful method, to variable selection
      is reported using different experimental datasets including FTIR and NIR data, so
      as to undertake classification and multivariate calibration tasks. Accordingly,
      invasive weed optimization - linear discrimination analysis (IWO-LDA) and
      invasive weed optimization- partial least squares (IWO-PLS) are introduced for
      multivariate classification and calibration, respectively.

PMID- 29353217
TI  - Vibrational spectroscopic study of cationic phosphorus dendrimers with
      aminoethylpiperidine terminal groups.
AB  - Two generations of phosphoric dendrimers with piperidine functional groups were
      synthesized for use in biology and medicine. Neutral samples are soluble in
      organic solvents but after protonation these dendrimers become water soluble and
      can be used for biological experiments. The FTIR and FT Raman spectra of two
      generations of dendrimers Gi constructed from the cyclotriphosphazene core,
      repeating units OC6H4CHNN(CH3)P(S)< and aminoethylpiperidine end groups
      NH(CH2)2C5NH11 were recorded. The study of the IR spectra shows that the NH
      groups form hydrogen bonds. The calculation of the molecular structure and
      vibrational spectra of the first generation dendrimer was performed by the method
      of DFT. This molecule has flat, repeating units and a plane of symmetry passing
      through the core. The calculation of the distribution of potential energy made it
      possible to classify the bands in the experimental spectra of dendrimers. Amine
      groups are manifested in the form of a band of NH stretching vibrations at 3389
      cm-1 in the IR spectrum of G1. NH+ stretching bands located at 2646 and 2540 cm-1
      in the IR spectrum of G2. The stretching vibrations of NH+ groups are noticeably
      shifted to low frequencies due to the formation of a hydrogen bond with the
      chlorine atom. The line at 1575 cm-1 in the Raman spectrum of G1 is
      characteristic for repeating units.

PMID- 29353218
TI  - Sulforaphane prevents angiotensin II-induced cardiomyopathy by activation of Nrf2
      via stimulating the Akt/GSK-3beta/Fyn pathway.
AB  - AIMS: Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by
      sulforaphane (SFN) protects from, and deletion of the Nrf2 gene exaggerates,
      diabetic cardiomyopathy. Angiotensin II (Ang II) plays a critical role in the
      development of diabetic cardiomyopathy. Therefore, whether SFN prevents Ang II
      induced cardiomyopathy through activation of Nrf2 was examined using wild-type,
      global deletion of Nrf2 gene (Nrf2-KO) and cardiomyocyte-specific overexpression
      of Nrf2 gene (Nrf2-TG) mice. METHODS AND RESULTS: Administration of a subpressor
      dose of Ang II to wild-type mice induced cardiac oxidative stress, inflammation,
      remodeling and dysfunction, all of which could be prevented by SFN treatment with
      Nrf2 up-regulation and activation. Nrf2-KO mice are susceptible, and Nrf2-TG mice
      are resistant, respectively, to Ang II-induced cardiomyopathy. Meanwhile, the
      ability of SFN to protect against Ang II-induced cardiac damage was lost in Nrf2
      KO mice. Up-regulation and activation of Nrf2 by SFN is accompanied by activation
      of Akt, inhibition of glycogen synthase kinase (GSK)-3beta, and accumulation of
      Fyn in nuclei. In vitro up-regulation of Nrf2 by SFN was abolished and nuclear
      Fyn accumulation was increased when cardiac cells were exposed to a PI3K
      inhibitor or GSK-3beta-specific activator. CONCLUSION: These results suggest that
      Nrf2 plays a central role in the prevention of Ang II-induced cardiomyopathy, and
      SFN prevents Ang II-induced cardiomyopathy partially via the Akt/GSK-3beta/Fyn
      mediated Nrf2 activation.

PMID- 29353220
TI  - Quantification of spheno-occipital synchondrosis fusion in a contemporary
      Malaysian population.
AB  - Timing of fusion of the spheno-occipital synchondrosis (SOS) is correlated with
      age. Previous research, however, has demonstrated variation in the timing of
      closure among different global populations. The present study aims to quantify
      the timing of SOS fusion in Malaysian individuals as visualised in multi-detector
      computed tomography (CT) scans and to thereafter formulate age estimation models
      based on fusion status. Anonymised cranial CT scans of 336 males and 164 females,
      aged 5-25 years, were acquired from the National Institute of Forensic Medicine,
      Hospital Kuala Lumpur and Department of Diagnostic Imaging, Hospital Sultanah
      Aminah. The scans were received in DICOM format and reconstructed into three
      dimensional images using OsiriX. The SOS is scored as open, fusing endocranially,
      fusing ectocranially or completely fused. Statistical analyses are performed
      using IBM SPSS Statistics version 24. Transition analysis (Nphases2) is then
      utilised to calculate age ranges for each stage. To assess the reliability of an
      observation, intra- and inter-observer agreement is quantified using Fleiss Kappa
      and was found to be excellent (kappa=0.785-0.907 and 0.812). The mean (SD) age
      for complete fusion is 20.84 (2.84) years in males and 19.78 (3.35) years in
      females. Transition ages between Stages 0 and 1, 1 and 2, and 2 and 3 in males
      are 12.52, 13.98 and 15.52 years, respectively (SD 1.37); in females, the
      corresponding data are 10.47, 12.26 and 13.80 years (SD 1.72). Complete fusion of
      the SOS was observed in all individuals above the age of 18 years. SOS fusion
      status provides upper and lower age boundaries for forensic age estimation in the
      Malaysian sample.

PMID- 29353221
TI  - An in-frame deletion in BICD2 associated with a non-progressive form of SMALED.

PMID- 29353219
TI  - Blocking mitochondrial cyclophilin D ameliorates TSH-impaired defensive barrier
      of artery.
AB  - AIMS: Endothelial cells (ECs) constitute the defensive barrier of vasculature,
      which maintains the vascular homeostasis. Mitochondrial oxidative stress (mitoOS)
      in ECs significantly affects the initiation and progression of vascular diseases.
      The higher serum thyroid stimulating hormone (TSH) level is being recognized as a
      nonconventional risk factor responsible for the increased risk of cardiovascular
      diseases in subclinical hypothyroidism (SCH). However, effects and underlying
      mechanisms of elevated TSH on ECs are still ambiguous. We sought to investigate
      whether cyclophilin D (CypD), emerging as a crucial mediator in mitoOS, regulates
      effects of TSH on ECs. METHODS AND RESULTS: SCH patients with TSH > = 10mIU/L
      showed a positive correlation between serum TSH and endothelin-1 levels. When TSH
      levels declined to normal in these subjects after levothyroxine therapy, serum
      endothelin-1 levels were significantly reduced. Supplemented with exogenous
      thyroxine to keep normal thyroid hormones, thyroid-specific TSH receptor (TSHR)
      knockout mice with injection of exogenous TSH exhibited elevated serum TSH
      levels, significant endothelial oxidative injuries and disturbed endothelium
      dependent vasodilation. However, Tshr-/- mice resisted to TSH-impaired vasotonia.
      We further confirmed that elevated TSH triggered excessive mitochondrial
      permeability transition pore (mPTP) opening and mitochondrial oxidative damages
      in mouse aorta, as well as in cultured ECs. Genetic or pharmacological inhibition
      of CypD (the key regulator for mPTP opening) attenuated TSH-induced mitochondrial
      oxidative damages and further rescued endothelial functions. Finally, we
      confirmed that elevated TSH could activate CypD by enhancing CypD acetylation via
      inhibiting adenosine monophosphate-activated protein kinase/sirtuin-3 signaling
      pathway in ECs. CONCLUSIONS: These findings reveal that elevated TSH triggers
      mitochondrial perturbations in ECs and provide insights that blocking
      mitochondrial CypD enhances the defensive ability of ECs under TSH exposure.

PMID- 29353222
TI  - Cohort study of cervical ossification of posterior longitudinal ligament in a
      Korean populations: Demographics of prevalence, surgical treatment, and
      disability.
AB  - OBJECTIVE: To investigate the demographic characteristics of cervical
      ossification of posterior longitudinal ligament (OPLL) including prevalence,
      surgical treatment, and disability in Korean population using Korean National
      Health Insurance Service National Sample Cohort (NHIS-NSC) data, and to analyze
      association between accessibility for surgical treatment and socioeconomic
      factors. PATIENTS AND METHODS: A population-based cohort study was conducted
      using stratified representative sampling from NHIS-NSC data from the year 2002 to
      2013. We analyzed prevalence and distribution of cervical OPLL according to age,
      sex, and socioeconomic factors. Multiple logistic regression analysis was
      conducted to investigate associations between independent variables and the rate
      of surgical treatment. RESULTS: The overall prevalence of cervical OPLL was 190
      per 100,000 people in Korea, and 11.4% of male patients and 4.0% of female
      patients received surgical treatment. Logistic regression analysis revealed that
      male patients received more surgical treatment than did female patients, also
      income level and residential area influence the rate of surgical treatment in
      females after adjustment of covariates (p< 0.05). Disability rate associated with
      cervical OPLL was 2.27% in male and 0.99% in female patients. CONCLUSION: In this
      cohort study, the prevalence of cervical OPLL was 190 per 100,000 people. Male
      patients received more surgery, and disability rate of male was higher than
      female patients. Although surgical treatment is covered by medical insurance in
      Korea, socioeconomic factors such as income level and residential area influence
      the treatment plans in females. These findings can help in the understanding of
      disease progression and can inform surgical treatment plans to reduce disability.

PMID- 29353223
TI  - Parathyroid carcinoma: From a case report to a review of the literature.
AB  - INTRODUCTION: Parathyroid carcinoma is a rare endocrine malignancy. The reported
      incidence is from 0.5 to 5% of primary hyperparathyroidism cases in various
      series. Consideration of parathyroid carcinoma in the differential diagnosis of
      hypercalcaemic disorders is important because the morbidity and mortality are
      substantial and the best prognosis is associated with early recognition and
      surgical resection. PRESENTATION OF CASE: We report a case of parathyroid
      carcinoma occurring in a 60-year-old woman who presented to our institution with
      persistent hyperparathyroidism and hypercalcemia 3 years after being submitted to
      one gland parathyroidectomy in another hospital. DISCUSSION AND CONCLUSION: A
      review of the related literature follows.

PMID- 29353224
TI  - Coronary microvascular dysfunction may be related to IGF-1 in acromegalic
      patients and can be restored by therapy.
AB  - BACKGROUND AND AIMS: Acromegaly increases the risk of cardiovascular mortality.
      Data on the cardiovascular risk in asymptomatic acromegaly are limited. In
      particular, data on coronary microvascular abnormalities are lacking. We assessed
      coronary flow reserve (CFR) as a marker of coronary microvascular function in
      asymptomatic acromegaly. METHODS: We studied 40 acromegalic patients (23 male,
      age 52 +/- 11 years) without clinical evidence of cardiovascular disease, and 40
      control subjects matched for age and sex. Coronary flow velocity in the left
      anterior descending coronary artery was detected by transthoracic Doppler
      echocardiography, at rest, and during adenosine infusion. CFR was the ratio of
      hyperaemic to resting diastolic flow velocity. RESULTS: CFR was lower in patients
      than in controls (2.9 +/- 0.8 vs. 3.7 +/- 0.6, p < 0.0001) and was abnormal
      (<=2.5) in 13 patients (32.5%) compared with any control subjects (0%) (p <
      0.0001). CFR was inversely related to insulin-like growth factor 1 (IGF-1) levels
      (r = -0.5, p < 0.004). In patients with CFR<=2.5, IGF-1 was higher (756 [381-898]
      MUg/l versus 246 [186-484] MUg/l, p < 0.007) whereas growth hormone (GH) levels
      were similar (6.3 [2.8-13.7] MUg/l versus 5 [2.8-8.9] MUg/l, p = 0.8). In
      multivariable linear regression analysis, IGF-1 was independently associated with
      CFR (p < 0.0001). In multiple logistic regression analysis, IGF-1 independently
      increased the probability of CFR<=2.5 (p = 0.009). In four patients with active
      disease (all with CFR<2.5), treatment with somatostatin analogues normalized CFR.
      However the other four patients with active disease were not responder.
      CONCLUSIONS: Acromegalic patients have coronary microvascular dysfunction that
      may be restored by therapy with somatostatin analogues. IGF-1 independently
      correlates with the coronary microvascular impairment, suggesting the pivotal
      role of this hormone in explaining the increased cardiovascular risk in
      acromegaly.

PMID- 29353225
TI  - Spectrum of mutations in index patients with familial hypercholesterolemia in
      Singapore: Single center study.
AB  - BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is an autosomal dominant
      genetic disease characterized by the presence of high plasma low density
      lipoproteins cholesterol (LDL-c). Patients with FH, with mutation detected, are
      at increased risk of premature cardiovascular disease compared to those without
      mutations. The aim of the study was to assess the type of mutations in patients,
      clinically diagnosed with FH in Singapore. METHODS: Patients (probands) with
      untreated/highest on-treatment LDL-c>4.9 mmol/l were recruited (June 2015 to
      April 2017). Anthropometric, biochemical indices, blood and family history were
      collected. DNA was extracted and Next Generation Sequencing (NGS) was performed
      in 26 lipid-related genes, including LDLR, APOB and PCSK9, and validated using
      Sanger. Multiplex-ligation probe analyses for LDLR were performed to identify
      large mutation derangements. Based on HGVS nomenclature, LDLR mutations were
      classified as "Null"(nonsense, frameshift, large rearrangements) and
      "Defective"(point mutations which are pathogenic). RESULTS: Ninety-six probands
      were recruited: mean age: (33.5 +/- 13.6) years. 52.1% (n = 50) of patients had
      LDLR mutations, with 15 novel mutations, and 4.2% (n = 4) had APOB mutations.
      Total cholesterol (TC) and LDL-c were significantly higher in those with LDLR
      mutations compared to APOB and no mutations [(8.53 +/- 1.52) vs. (6.93 +/- 0.47)
      vs. (7.80 +/- 1.32)] mmol/l, p = 0.012 and [(6.74 +/- 0.35) vs. (5.29 +/- 0.76)
      vs. (5.98 +/- 1.23)] mmol/l, p=0.005, respectively. Patients with "null LDLR"
      mutations (n = 13) had higher TC and LDL-c than "defective LDLR" mutations (n =
      35): [(9.21 +/- 1.60) vs. (8.33 +/- 1.41)]mmol/l, p = 0.034 and [(7.43 +/- 1.47)
      vs. (6.53 +/- 1.21)]mmol/l, p=0.017, respectively. CONCLUSIONS: To our knowledge,
      this is the first report of mutation detection in patients with clinically
      suspected FH by NGS in Singapore. While percentage of mutations is similar to
      other countries, the spectrum locally differs.

PMID- 29353226
TI  - High neutrophil to lymphocyte ratios predict intracranial atherosclerosis in a
      healthy population.
AB  - BACKGROUND AND AIMS: Although atherosclerosis has been shown to be an
      inflammatory disease, intracranial atherosclerosis (ICAS) has not been well
      addressed. The purpose of this study was to evaluate the relationship between the
      neutrophil to lymphocyte ratio (NLR) and the presence of ICAS lesions in a
      generally healthy population. METHODS: A consecutive series of subjects, who
      voluntarily visited for health check-ups between January 2006 and December 2013,
      were selected. Brain magnetic resonance imaging, brain magnetic angiography
      (MRA), and blood cell count data were assessed. ICAS was defined as an occlusion
      or more than 50% stenosis of intracranial vessels, as observed on brain MRA
      images. NLR was calculated based on absolute neutrophil and lymphocyte counts.
      RESULTS: A total of 2842 subjects were evaluated, and 76 ICAS cases were found.
      The median NLR was 1.52 [1.17-2.01]. In multivariate analysis, NLR remained an
      independent predictor of ICAS [adjusted OR (aOR) = 1.72, 95% confidence interval
      (CI) = 1.01-2.95, p = 0.048]. Age (aOR = 1.08, 95% CI = 1.05-1.11, p < 0.001) and
      hypertension (aOR = 1.81, 95% CI = 1.11-2.94, p = 0.017) were also significant
      factors for ICAS independent of NLR. Regarding ICAS burdens, NLR was
      significantly higher when the number of ICAS lesions (p = 0.017) or occlusive
      ICAS lesions (p = 0.005) was increased in a dose-response manner. CONCLUSIONS: A
      high NLR was associated with both prevalence and burdens of ICAS in a healthy
      population.

PMID- 29353227
TI  - The natural history of phytosterolemia: Observations on its homeostasis.
AB  - BACKGROUND AND AIMS: Phytosterolemia is a rare genetic disease caused by mutation
      of the ABCG5/8 gene. Our aim was to elucidate the natural history and homeostasis
      of phytosterolemia. METHODS: We analyzed a Hutterite kindred consisting of 21
      homozygotes with phytosterolemia assembled over a period of two decades, all of
      whom carried the ABCG8 S107X mutation and were treated with ezetimibe. RESULTS:
      Most of these subjects were asymptomatic and devoid of clinical stigmata, and
      this, since they were ascertained primarily by a process of cascade testing,
      suggests that, relative to its true prevalence, phytosterolemia is a condition of
      low morbidity. All subjects have responded well to treatment with ezetimibe.
      Initial (pre-treatment) and post-ezetimibe levels of cholesterol and sitosterol
      were measured and percentage changes on ezetimibe were calculated. We found
      initial levels to be inversely related to subjects' ages as were percentage
      responses to ezetimibe therapy. There was also a direct correlation between
      initial levels and percentage responses to ezetimibe. Hence on-treatment levels
      were very uniform. CONCLUSIONS: This evidence of a link with age leads us to
      propose that an age-related change in cholesterol and sterol homeostasis occurs
      at puberty in phytosterolemia and that the change is due to high sterol and/or
      stanol levels causing feedback inhibition of sterol regulatory element-binding
      protein (SREBP-2) processing. This would explain the well-documented phenomenon
      of depressed cholesterol synthesis in phytosterolemia. It is also well-known that
      LDL-receptor activity is increased, and this feasibly explains reduced LDL levels
      and consequent reduction of plasma cholesterol and sitosterol levels.
      Downregulated SREBP-2 processing would be expected to also lower proprotein
      convertase subtilisin/kexin type 9 (PCSK9) levels and this would explain high LDL
      receptor activity. The above state could be termed disrupted homeostasis and the
      alternative, seen mostly in children and characterized by hypercholesterolemia
      and hypersterolemia, simple homeostasis.

PMID- 29353228
TI  - Association of lifelong occupation and educational level with subclinical
      atherosclerosis in different European regions. Results from the IMPROVE study.
AB  - BACKGROUND AND AIMS: We aimed to examine the association between socioeconomic
      status (SES) and subclinical atherosclerosis, as assessed by carotid intima-media
      thickness (C-IMT) and to investigate whether the effect of social inequality on C
      IMT is mediated by cardiovascular (CV) risk factors and whether it is dissimilar
      in men and women, and in different European countries. METHODS: We assessed the
      association of lifelong occupation and educational level with C-IMT in the
      IMPROVE study cohort including 3703 subjects (median age 64.4 years; 48% men)
      from Southern (Italy), Western (France and the Netherlands) and Northern Europe
      (Finland and Sweden). Three summary measures of C-IMT (IMTmean, IMTmax, IMTmean
      max), obtained from four segments of both carotids, were considered. RESULTS:
      After adjusting for conventional CV risk factors, current employment status and
      diet, C-IMT was higher in manual workers than in white collars (+7.7%, +5.3%,
      +4.6% for IMTmax, IMTmean-max and IMTmean, respectively; all p<.0001). Similar
      results were obtained by stratification for educational level. The effect of
      occupation on C-IMT was comparable in men and women and in different age groups,
      and was only partially mediated by differences in CV risk factors. Of note, the
      association of C-IMT with occupation was significant in Western and Northern
      Europe but not in Italy, with a significant statistical interaction (p = .0005).
      CONCLUSIONS: Low SES was associated with subclinical atherosclerosis in subjects
      with at least three CV risk factors. Such association was stronger in Northern
      and Western Europe than in Italy. This difference was not completely explained by
      inequalities in CV risk factors and behavioural variables.

PMID- 29353229
TI  - The association between plasma endotoxin, endotoxin pathway proteins and outcome
      after ischemic stroke.
AB  - BACKGROUND AND AIMS: In animals, peripheral lipopolysaccharide (LPS) injection
      before cerebral ischemia exacerbates neurological deficit, impairs survival and
      augments sickness behaviour. The goal of our study was to determine a
      relationship between plasma LPS, LPS pathway proteins (LPS binding protein (LBP)
      and sCD14) and outcome in stroke patients. METHODS: We included 335 patients with
      ischemic stroke. Plasma LPS activity and levels of LBP and sCD14 were measured
      within 24 h after stroke onset. The endpoints of this study were (1) 3-month poor
      functional outcome defined as a modified Rankin Scale score >2; (2) 3-month and
      12-month case fatality; (3) delirium during the first 7 days after admission.
      RESULTS: Plasma LPS activity did not correlate with either functional outcome or
      mortality. The higher levels of LBP and sCD14 predicted 3-month and 12-month case
      fatality. The adjusted hazard ratio for 12-month case fatality was 1.84 (95% CI:
      1.32-2.58, p < 0.01) for LBP and 1.62 (95% CI: 1.15-2.29, p < 0.01) for sCD14. On
      multivariate analysis, higher LPS activity (OR: 1.63, 95% CI: 1.15-2.31, p =
      0.01) and higher LBP (OR: 1.44, 95% CI: 1.04-2.00, p = 0.03) and sCD14 levels
      (OR: 1.54, 95% CI: 1.12-2.13, p = 0.01) were associated with increased risk of
      delirium. CONCLUSIONS: In ischemic stroke patients, higher levels of plasma sCD14
      and LBP are associated with increased risk of death, whereas, elevated LPS
      activity and higher levels of LBP and CD14 are associated with post-stroke
      delirium.

PMID- 29353230
TI  - A Model of Dormant-Emergent Metastatic Breast Cancer Progression Enabling
      Exploration of Biomarker Signatures.
AB  - Breast cancer mortality predominantly results from dormant micrometastases that
      emerge as fatal outgrowths years after initial diagnosis. In order to gain
      insights concerning factors associated with emergence of liver metastases, we
      recreated spontaneous dormancy in an all-human ex vivo hepatic microphysiological
      system (MPS). Seeding this MPS with small numbers (<0.05% by cell count) of the
      aggressive MDA-MB-231 breast cancer cell line, two populations formed: actively
      proliferating ("growing"; EdU+), and spontaneously quiescent ("dormant"; EdU-).
      Following treatment with a clinically standard chemotherapeutic, the
      proliferating cells were eliminated and only quiescent cells remained; this
      residual dormant population could then be induced to a proliferative state
      ("emergent"; EdU+) by physiologically-relevant inflammatory stimuli,
      lipopolysaccharide (LPS) and epidermal growth factor (EGF). Multiplexed proteomic
      analysis of the MPS effluent enabled elucidation of key factors and processes
      that correlated with the various tumor cell states, and candidate biomarkers for
      actively proliferating (either primary or secondary emergence) versus dormant
      metastatic cells in liver tissue. Dormancy was found to be associated with
      signaling reflective of cellular quiescence even more strongly than the original
      tumor-free liver tissue, whereas proliferative nodules presented inflammatory
      signatures. Given the minimal tumor burden, these markers likely represent
      changes in the tumor microenvironment rather than in the tumor cells. A
      computational decision tree algorithm applied to these signatures indicated the
      potential of this MPS for clinical discernment of each metastatic stage from
      blood protein analysis.

PMID- 29353231
TI  - The Preterm Heart in Childhood: Left Ventricular Structure, Geometry, and
      Function Assessed by Echocardiography in 6-Year-Old Survivors of Periviable
      Births.
AB  - BACKGROUND: Preterm birth has been associated with increased risk of
      cardiovascular morbidity in adult life. We evaluated whether preterm birth is
      associated with deviating cardiac structure and function before school start.
      METHODS AND RESULTS: In total, 176 children aged 6 years and born extremely
      preterm (EXPT; gestational age of 22-26 weeks) and 134 children born at term
      (control [CTRL]) were studied. We used echocardiography to assess left heart
      dimensions, geometry, and functions. Recording and off-line analyses of
      echocardiographic images were performed by operators blinded to group belonging.
      Body size, blood pressure, and heart rate were also measured. Rates of family
      history of cardiovascular disease and sex distribution were similar in the EXPT
      and CTRL groups. Heart rate and systolic blood pressure did not differ, whereas
      diastolic blood pressure was slightly higher in EXPT than CTRL participants.
      After adjusting for body surface area, left ventricular length, width, and aortic
      valve annulus diameter were 3% to 5% smaller in EXPT than CTRL participants. Left
      ventricular longitudinal shortening and systolic tissue velocity were 7% to 11%
      lower, and transversal shortening fraction was 6% higher in EXPT than CTRL
      participants. The EXPT group also exhibited lower atrial emptying velocities than
      the CTRL group. Sex, fetal growth restriction, or a patent ductus arteriosus in
      the neonatal period did not contribute to cardiac dimensions or performance.
      CONCLUSIONS: Six-year-old children born extremely preterm exhibit a unique
      cardiac phenotype characterized by smaller left ventricles with altered systolic
      and diastolic functions than same-aged children born at term.

PMID- 29353232
TI  - Albuminuria Increases the Risks for Both Alzheimer Disease and Vascular Dementia
      in Community-Dwelling Japanese Elderly: The Hisayama Study.
AB  - BACKGROUND: Epidemiologic evidence has emerged to reveal an association of
      albuminuria and low estimated glomerular filtration rate (eGFR) with dementia,
      but the findings are inconsistent. In addition, there are limited studies
      addressing the association between albuminuria and Alzheimer disease (AD).
      METHODS AND RESULTS: A total of 1562 community-dwelling Japanese subjects aged
      >=60 years without dementia were followed up for 10 years. The outcomes were
      incidence of all-cause dementia and its subtypes, namely, AD and vascular
      dementia (VaD). The hazard ratios for the outcomes were estimated according to
      urine albumin-creatinine ratio (UACR) and eGFR levels using a Cox proportional
      hazards model. During the follow-up, 358 subjects developed all-cause dementia
      (238 AD and 93 VaD). Higher UACR level was significantly associated with greater
      multivariable-adjusted risks of all-cause dementia (hazard ratios [95% confidence
      intervals]: 1.00 [reference], 1.12 [0.78-1.60], 1.65 [1.18-2.30], and 1.56 [1.11
      2.19] for UACR of <=6.9, 7.0-12.7, 12.8-29.9, and >=30.0 mg/g, respectively), AD
      (1.00 [reference], 1.20 [0.77-1.86], 1.75 [1.16-2.64], and 1.58 [1.03-2.41],
      respectively), and VaD (1.00 [reference], 1.03 [0.46-2.29], 1.94 [0.96-3.95], and
      2.19 [1.09-4.38], respectively). On the other hand, lower eGFR level was
      marginally associated with greater risk of VaD, but not AD. Subjects with UACR
      >=12.8 mg/g and eGFR of <60 mL/min per 1.73 m2 had 3.3-fold greater risk of VaD
      than those with UACR <12.8 mg/g and eGFR of >=60 mL/min per 1.73 m2. CONCLUSIONS:
      Albuminuria is a significant risk factor for the development of both AD and VaD
      in community-dwelling Japanese elderly. Moreover, albuminuria and low eGFR are
      mutually associated with a greater risk of VaD.

PMID- 29353233
TI  - Cardiovascular Safety, Long-Term Noncardiovascular Safety, and Efficacy of Sodium
      Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A
      Systemic Review and Meta-Analysis With Trial Sequential Analysis.
AB  - BACKGROUND: The cardiovascular and long-term noncardiovascular safety and
      efficacy of SGLT2 (sodium-glucose cotransporter 2) inhibitors have not been well
      documented. METHODS AND RESULTS: For cardiovascular outcomes, we performed a meta
      analysis with trial sequential analysis of randomized controlled trials and
      adjusted observational studies, each with a minimum of 26 weeks and 2000 patient
      years of follow-up. For long-term noncardiovascular safety and efficacy outcome
      analyses, we included only randomized controlled trials with at least 2 years and
      1000 patient-years of follow-up. Five studies with 351 476 patients were included
      in cardiovascular outcomes analysis. Meta-analyses showed that SGLT2 inhibitors
      significantly reduced the risks of major adverse cardiac events (hazard ratio
      [HR]: 0.80; 95% confidence interval [CI], 0.69-0.92; P=0.002), all-cause
      mortality (HR: 0.67; 95% CI, 0.54-0.84; P<0.001), cardiovascular mortality (HR:
      0.77; 95% CI, 0.60-0.98; P=0.03), nonfatal myocardial infarction (HR: 0.86; 95%
      CI, 0.76-0.98; P=0.02), hospitalization for heart failure (HR: 0.62; 95% CI, 0.55
      0.69; P<0.001), and progression of albuminuria (HR: 0.68; 95% CI, 0.58-0.81;
      P<0.001). No significant difference in nonfatal stroke was found. Analyses
      limited to randomized controlled trials showed similar findings. Trial sequential
      analysis provided firm evidence of a 20% reduction in major adverse cardiac
      events, all-cause mortality, and hospitalization for heart failure with SGLT2
      inhibitors, but evidence remains inconclusive for cardiovascular mortality. Nine
      randomized controlled trials contributed to long-term noncardiovascular and
      efficacy analyses. SGLT2 inhibitors reduced incidence of hypoglycemia and acute
      kidney injury but increased the risks of urinary tract and genital infections.
      CONCLUSIONS: SGLT2 inhibitors showed remarkable cardiovascular- and renal
      protective effects and good long-term noncardiovascular safety with sustained
      efficacy.

PMID- 29353234
TI  - Psychiatric symptoms in preclinical behavioural-variant frontotemporal dementia
      in MAPT mutation carriers.
AB  - OBJECTIVE: To characterise psychiatric symptoms in preclinical and early
      behavioural-variant frontotemporal dementia (bvFTD), a neurodegenerative disorder
      whose symptoms overlap with and are often mistaken for psychiatric illness.
      METHODS: The present study reports findings from a systematic, global,
      prospective evaluation of psychiatric symptoms in 12 preclinical carriers of
      pathogenic MAPT mutations, not yet meeting bvFTD diagnostic criteria, and 46
      familial non-carrier controls. Current psychiatric symptoms, informant-reported
      symptoms and lifetime prevalence of psychiatric disorders were assessed with The
      Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV) and the Neuropsychiatric Inventory
      Questionnaire. Fisher exact test was used to compare carriers and non-carriers'
      lifetime prevalence of six DSM-IV disorders: major depressive disorder, panic
      attacks, alcohol abuse, generalised anxiety disorder, panic disorder, and
      depressive disorder not otherwise specified. Other DSM-IV disorders had
      insufficient prevalence across our sample for between-group comparisons, but are
      reported. RESULTS: Non-carriers had greater prevalence of mood and anxiety
      disorders than has been reported for a general reference population. Preclinical
      carriers had lower lifetime prevalence of mood and anxiety disorders than non
      carriers, except for depressive disorder not otherwise specified, an atypical
      syndrome comprising clinically significant depressive symptoms which fail to meet
      criteria for major depressive disorder. CONCLUSION: Findings suggest that early
      psychiatric symptoms of emergent bvFTD may manifest as emotional blunting or mood
      changes not cleanly conforming to criteria for a DSM-defined mood disorder.

PMID- 29353235
TI  - Iron.ic facts about dementia.

PMID- 29353236
TI  - Deep brain stimulation for Parkinson's disease: defining the optimal location
      within the subthalamic nucleus.
AB  - BACKGROUND: Individual motor improvement after deep brain stimulation (DBS) of
      the subthalamic nucleus (STN) for Parkinson's disease (PD) varies considerably.
      Stereotactic targeting of the dorsolateral sensorimotor part of the STN is
      considered paramount for maximising effectiveness, but studies employing the
      midcommissural point (MCP) as anatomical reference failed to show correlation
      between DBS location and motor improvement. The medial border of the STN as
      reference may provide better insight in the relationship between DBS location and
      clinical outcome. METHODS: Motor improvement after 12 months of 65 STN DBS
      electrodes was categorised into non-responding, responding and optimally
      responding body-sides. Stereotactic coordinates of optimal electrode contacts
      relative to both medial STN border and MCP served to define theoretic DBS
      'hotspots'. RESULTS: Using the medial STN border as reference, significant
      negative correlation (Pearson's correlation -0.52, P<0.01) was found between the
      Euclidean distance from the centre of stimulation to this DBS hotspot and motor
      improvement. This hotspot was located at 2.8 mm lateral, 1.7 mm anterior and 2.5
      mm superior relative to the medial STN border. Using MCP as reference, no
      correlation was found. CONCLUSION: The medial STN border proved superior compared
      with MCP as anatomical reference for correlation of DBS location and motor
      improvement, and enabled defining an optimal DBS location within the nucleus. We
      therefore propose the medial STN border as a better individual reference point
      than the currently used MCP on preoperative stereotactic imaging, in order to
      obtain optimal and thus less variable motor improvement for individual patients
      with PD following STN DBS.

PMID- 29353237
TI  - Beyond motor neurons: expanding the clinical spectrum in Kennedy's disease.
AB  - Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA), is an X-linked
      neuromuscular condition clinically characterised by weakness, atrophy and
      fasciculations of the limb and bulbar muscles, as a result of lower motor neuron
      degeneration. The disease is caused by an abnormally expanded triplet repeat
      expansions in the ubiquitously expressed androgen receptor gene, through
      mechanisms which are not entirely elucidated. Over the years studies from both
      humans and animal models have highlighted the involvement of cell populations
      other than motor neurons in SBMA, widening the disease phenotype. The most
      compelling aspect of these findings is their potential for therapeutic impact:
      muscle, for example, which is primarily affected in the disease, has been
      recently shown to represent a valid alternative target for therapy to motor
      neurons. In this review, we discuss the emerging study of the extra-motor neuron
      involvement in SBMA, which, besides increasingly pointing towards a
      multidisciplinary approach for affected patients, deepens our understanding of
      the pathogenic mechanisms and holds potential for providing new therapeutic
      targets for this disease.

PMID- 29353238
TI  - Multimodal spinal cord MRI offers accurate diagnostic classification in ALS.

PMID- 29353239
TI  - Altered eicosanoid production and phospholipid remodeling during cell culture.
AB  - The remodeling of PUFAs by the Lands cycle is responsible for the diversity of
      phospholipid molecular species found in cells. There have not been detailed
      studies of the alteration of phospholipid molecular species as a result of serum
      starvation or depletion of PUFAs that typically occurs during tissue culture. The
      time-dependent effect of cell culture on phospholipid molecular species in RAW
      264.7 cells cultured for 24, 48, or 72 h was examined by lipidomic strategies.
      These cells were then stimulated to produce arachidonate metabolites derived from
      the cyclooxygenase pathway, thromboxane B2, PGE2, and PGD2, and the 5
      lipoxygenase pathway, leukotriene (LT)B4, LTC4, and 5-HETE, which decreased with
      increasing time in culture. However, the 5-lipoxygenase metabolites of a 20:3
      fatty acid, LTB3, all trans-LTB3, LTC3, and 5-hydroxyeicosatrienoic acid, time
      dependently increased. Molecular species of arachidonate containing phospholipids
      were drastically remodeled during cell culture, with a new 20:3 acyl group being
      populated into phospholipids to replace increasingly scarce arachidonate. In
      addition, the amount of TNFalpha induced by lipopolysaccharide stimulation was
      significantly increased in the cells cultured for 72 h compared with 24 h,
      suggesting that the remodeling of PUFAs enhanced inflammatory response. These
      studies supported the rapid operation of the Lands cycle to maintain cell growth
      and viability by populating PUFA species; however, without sufficient n-6 fatty
      acids, 20:3 n-9 accumulated, resulting in altered lipid mediator biosynthesis and
      inflammatory response.

PMID- 29353240
TI  - PIP4K2A regulates intracellular cholesterol transport through modulating
      PI(4,5)P2 homeostasis.
AB  - The transport of LDL-derived cholesterol from lysosomes to peroxisomes is
      facilitated by membrane contacts formed between the lysosomal protein
      synaptotagmin VII and the peroxisomal lipid phosphatidylinositol 4, 5
      bisphosphate [PI(4,5)P2]. Here, we used RNA interference to search for regulators
      of PI(4,5)P2 and to study the effects of altered PI(4,5)P2 homeostasis on
      cholesterol transport. We found that knockdown of phosphatidylinositol 5
      phosphate 4-kinase type-2 alpha (PIP4K2A) reduced peroxisomal PI(4,5)P2 levels,
      decreased lysosome-peroxisome membrane contacts, and increased accumulation of
      lysosomal cholesterol in human SV-589 fibroblasts. Forced expression of
      peroxisome-localized, kinase-active PIP4K2A in the knockdown cells reduced
      cholesterol accumulation, and in vitro addition of recombinant PIP4K2A restored
      membrane contacts. These results suggest that PIP4K2A plays a critical role in
      intracellular cholesterol transport by upregulating PI(4,5)P2 levels in the
      peroxisomal membrane. Further research into PIP4K2A activity may inform future
      therapeutic interventions for managing lysosomal storage disorders.

PMID- 29353241
TI  - Inhibition of Endothelial Notch Signaling Impairs Fatty Acid Transport and Leads
      to Metabolic and Vascular Remodeling of the Adult Heart.
AB  - BACKGROUND: Nutrients are transported through endothelial cells before being
      metabolized in muscle cells. However, little is known about the regulation of
      endothelial transport processes. Notch signaling is a critical regulator of
      metabolism and angiogenesis during development. Here, we studied how genetic and
      pharmacological manipulation of endothelial Notch signaling in adult mice affects
      endothelial fatty acid transport, cardiac angiogenesis, and heart function.
      METHODS: Endothelial-specific Notch inhibition was achieved by conditional
      genetic inactivation of Rbp-jkappa in adult mice to analyze fatty acid metabolism
      and heart function. Wild-type mice were treated with neutralizing antibodies
      against the Notch ligand Delta-like 4. Fatty acid transport was studied in
      cultured endothelial cells and transgenic mice. RESULTS: Treatment of wild-type
      mice with Delta-like 4 neutralizing antibodies for 8 weeks impaired fractional
      shortening and ejection fraction in the majority of mice. Inhibition of Notch
      signaling specifically in the endothelium of adult mice by genetic ablation of
      Rbp-jkappa caused heart hypertrophy and failure. Impaired heart function was
      preceded by alterations in fatty acid metabolism and an increase in cardiac blood
      vessel density. Endothelial Notch signaling controlled the expression of
      endothelial lipase, Angptl4, CD36, and Fabp4, which are all needed for fatty acid
      transport across the vessel wall. In endothelial-specific Rbp-jkappa-mutant mice,
      lipase activity and transendothelial transport of long-chain fatty acids to
      muscle cells were impaired. In turn, lipids accumulated in the plasma and liver.
      The attenuated supply of cardiomyocytes with long-chain fatty acids was
      accompanied by higher glucose uptake, increased concentration of glycolysis
      intermediates, and mTOR-S6K signaling. Treatment with the mTOR inhibitor
      rapamycin or displacing glucose as cardiac substrate by feeding a ketogenic diet
      prolonged the survival of endothelial-specific Rbp-jkappa-deficient mice.
      CONCLUSIONS: This study identifies Notch signaling as a novel regulator of fatty
      acid transport across the endothelium and as an essential repressor of
      angiogenesis in the adult heart. The data imply that the endothelium controls
      cardiomyocyte metabolism and function.

PMID- 29353242
TI  - Sickle cell crisis: A crisis of a different sort?
AB  - A 9-year-old boy with sickle cell disease (SCD) was presented to the emergency
      department with acute headache and swelling over his bilateral temporoparietal
      region. There was no history of antecedent trauma, fever, vomiting or other
      features of an intercurrent illness. On arrival, his blood pressure was 112/62 mm
      Hg, heart rate was 98/min and his Glasgow Coma Scale score was 15/15. There was
      evidence of significant scalp tenderness over the bilateral temporoparietal
      region. A complete neurological examination including direct and consensual
      pupillary response was unremarkable. Initial investigations revealed haemoglobin
      of 9.6 g/dL, leucocyte count of 6.8/mm3, platelet count of 219/mm3 and a normal
      coagulation profile. His current medications included hydroxyurea and penicillin
      prophylaxis. He underwent an urgent CT of the head followed by MRI of the brain,
      which revealed abnormalities as depicted in figures 1,2
      edpract;103/6/290/F1F1F1Figure 1CT head. edpract;103/6/290/F2F2F2Figure 2MRI
      brain. QUESTION 1: Is this one of the most common neurological presentation seen
      in sickle cell crisis? QUESTION 2: How common is this presentation in paediatric
      SCD? QUESTION 3: What is the best way to manage this child?

PMID- 29353244
TI  - Edge conditions and crash-avoidance roles: the future of traffic safety in the
      world of autonomous vehicles.

PMID- 29353243
TI  - Impact of order set design on urine culturing practices at an academic medical
      centre emergency department.
AB  - BACKGROUND: Urinalysis and urine culture are commonly ordered tests in the
      emergency department (ED). We evaluated the impact of removal of order sets from
      the 'frequently ordered test' in the computerised physician order entry system
      (CPOE) on urine testing practices. METHODS: We conducted a before (1 September to
      20 October 2015) and after (21 October to 30 November 2015) study of ED patients.
      The intervention consisted of retaining 'urinalysis with reflex to microscopy' as
      the only urine test in a highly accessible list of frequently ordered tests in
      the CPOE system. All other urine tests required use of additional order screens
      via additional mouse clicks. The frequency of urine testing before and after the
      intervention was compared, adjusting for temporal trends. RESULTS: During the
      study period, 6499 (28.2%) of 22 948 ED patients had >=1 urine test ordered.
      Urine testing rates for all ED patients decreased in the post intervention period
      for urinalysis (291.5 pre intervention vs 278.4 per 1000 ED visits post
      intervention, P=0.03), urine microscopy (196.5vs179.5, P=0.001) and urine culture
      (54.3vs29.7, P<0.001). When adjusted for temporal trends, the daily culture rate
      per 1000 ED visits decreased by 46.6% (-46.6%, 95% CI -66.2% to -15.6%), but
      urinalysis (0.4%, 95% CI -30.1 to 44.4%), microscopy (-6.5%, 95% CI -36.0% to
      36.6%) and catheterised urine culture rates (17.9%, 95% CI -16.9 to 67.4) were
      unchanged. CONCLUSIONS: A simple intervention of retaining only 'urinalysis with
      reflex to microscopy' and removing all other urine tests from the 'frequently
      ordered' window of the ED electronic order set decreased urine cultures ordered
      by 46.6% after accounting for temporal trends. Given the injudicious use of
      antimicrobial therapy for asymptomatic bacteriuria, findings from our study
      suggest that proper design of electronic order sets plays a vital role in
      reducing excessive ordering of urine cultures.

PMID- 29353245
TI  - New WHO Violence Prevention Information System, an interactive knowledge platform
      of scientific findings on violence.
AB  - Scientific information on violence can be difficult to compile and understand. It
      is scattered across websites, databases, technical reports and academic journals,
      and rarely addresses all types of violence. In response, in October 2017 WHO
      released the Violence Prevention Information System or Violence Info, an online
      interactive collection of scientific information about the prevalence,
      consequences, risk factors and preventability of all forms of interpersonal
      violence. It covers homicide, child maltreatment, youth violence, intimate
      partner violence, elder abuse and sexual violence.

PMID- 29353246
TI  - A concept mapping approach to identifying the barriers to implementing an
      evidence-based sports injury prevention programme.
AB  - BACKGROUND AND AIM: Understanding the barriers to programme use is important to
      facilitate implementation of injury prevention programmes in real-word settings.
      This study investigated the barriers to coaches of adolescent female soccer
      teams, in Victoria, Australia, implementing the evidence-based FIFA 11+ injury
      prevention programme. METHODS: Concept mapping with data collected from 19 soccer
      coaches and administrators. RESULTS: Brainstorming generated 65 statements as
      barriers to 11+ implementation. After the statements were synthesised and edited,
      participants sorted 59 statements into groups (mean, 6.2 groups; range, 3-10
      groups). Multidimensional scaling and hierarchical cluster analysis identified a
      six-cluster solution: Lack of 11+ knowledge among coaches (15 statements), Lack
      of player enjoyment and engagement (14), Lack of link to football-related goals
      (11), Lack of facilities and resources (8), Lack of leadership (6) and Lack of
      time at training (5). Statements in the 'Lack of 11+ knowledge among coaches'
      cluster received the highest mean importance (3.67 out of 5) and feasibility for
      the Football Federation to address (3.20) rating. Statements in the 'Lack of
      facilities and resources' cluster received the lowest mean importance rating
      (2.23), while statements in the 'Lack of time at training' cluster received the
      lowest mean feasibility rating (2.19). CONCLUSIONS: A multistrategy, ecological
      approach to implementing the 11+-with specific attention paid to improving coach
      knowledge about the 11+ and how to implement it, linking the 11+ to the primary
      goal of soccer training, and organisational leadership-is required to improve the
      uptake of the 11+ among the targeted coaches.

PMID- 29353247
TI  - Hydroxychloroquine-induced restrictive cardiomyopathy: a case report.

PMID- 29353248
TI  - Hypertrophic osteoarthropathy in a patient with known lung cancer.

PMID- 29353250
TI  - Loss of KRAS control as consequence of downregulated microRNA-622 in
      hepatocellular carcinoma and its potential therapeutic implication.

PMID- 29353251
TI  - Cardiopulmonary resuscitation: the science behind the hands.
AB  - Sudden cardiac arrest is a leading cause of death worldwide. Despite significant
      advances in resuscitation science since the initial use of external chest
      compressions in humans nearly 60 years ago, there continues to be wide
      variability in rates of successful resuscitation across communities. The American
      Heart Association (AHA) and European Resuscitation Council emphasise the
      importance of high-quality chest compressions as the foundation of resuscitation
      care. We review the physiological basis for the association between chest
      compression quality and clinical outcomes and the scientific basis for the AHA's
      key metrics for high-quality cardiopulmonary resuscitation. Finally, we highlight
      that implementation of strategies that promote effective chest compressions can
      improve outcomes in all patients with cardiac arrest.

PMID- 29353249
TI  - Plasma cell-free DNA methylation: a liquid biomarker of hepatic fibrosis.

PMID- 29353252
TI  - Systematic review of general practice end-of-life symptom control.
AB  - BACKGROUND: End of life care (EoLC) is a fundamental role of general practice,
      which will become more important as the population ages. It is essential that
      general practice's role and performance of at the end of life is understood in
      order to maximise the skills of the entire workforce. OBJECTIVE: To provide a
      comprehensive description of the role and performance of general practitioners
      (GPs) and general practice nurses (GPNs) in EoLC symptom control. METHOD:
      Systematic literature review of papers from 2000 to 2017 were sought from
      Medline, PsycINFO, Embase, Joanna Briggs Institute and Cochrane databases.
      RESULTS: From 6209 journal articles, 46 papers reported GP performance in symptom
      management. There was no reference to the performance of GPNs in any paper
      identified. Most GPs expressed confidence in identifying EoLC symptoms. However,
      they reported lack of confidence in providing EoLC at the beginning of their
      careers, and improvements with time in practice. They perceived emotional support
      as being the most important aspect of EoLC that they provide, but there were
      barriers to its provision. GPs felt most comfortable treating pain, and least
      confident with dyspnoea and depression. Observed pain management was sometimes
      not optimal. More formal training, particularly in the use of opioids was
      considered important to improve management of both pain and dyspnoea.
      CONCLUSIONS: It is essential that GPs receive regular education and training, and
      exposure to EoLC from an early stage in their careers to ensure skill and
      confidence. Research into the role of GPNs in symptom control needs to occur.

PMID- 29353253
TI  - Experiential learning to increase palliative care competence among the Indigenous
      workforce: an Australian experience.
AB  - OBJECTIVES: Improving Indigenous people's access to palliative care requires a
      health workforce with appropriate knowledge and skills to respond to end-of-life
      (EOL) issues. The Indigenous component of the Program of Experience in the
      Palliative Approach (PEPA) includes opportunities for Indigenous health
      practitioners to develop skills in the palliative approach by undertaking a
      supervised clinical placement of up to 5 days within specialist palliative care
      services. This paper presents the evaluative findings of the components of an
      experiential learning programme and considers the broader implications for
      delivery of successful palliative care education programme for Indigenous people.
      METHODS: Semistructured interviews were conducted with PEPA staff and Indigenous
      PEPA participants. Interviews were recorded, transcribed and key themes
      identified. RESULTS: Participants reported that placements increased their
      confidence about engaging in conversations about EOL care and facilitated
      relationships and ongoing work collaboration with palliative care services.
      Management support was critical and placements undertaken in settings which had
      more experience caring for Indigenous people were preferred. Better engagement
      occurred where the programme included Indigenous staffing and leadership and
      where preplacement and postplacement preparation and mentoring were provided.
      Opportunities for programme improvement included building on existing
      postplacement and follow-up activities. CONCLUSIONS: A culturally respectful
      experiential learning education programme has the potential to upskill Indigenous
      health practitioners in EOL care.

PMID- 29353255
TI  - Commentary: Heterogeneity of respiratory disease in children and young adults
      with sickle cell disease.

PMID- 29353254
TI  - The supportive relationship between palliative patients and family caregivers.

PMID- 29353256
TI  - Dieulafoy's disease with mediastinal arteriovenous malformation.

PMID- 29353257
TI  - Ethical dilemmas of recording and reviewing neonatal resuscitation.
AB  - Neonatal resuscitation is provided to approximately 3% of neonates. Adequate
      ventilation is often the key to successful resuscitation, but this can be
      difficult to provide. There is increasing evidence that inappropriate respiratory
      support can have severe consequences. Several neonatal intensive care units have
      recorded and reviewed neonatal resuscitation procedures for quality assessment,
      education and research; however, ethical dilemmas sometimes make it difficult to
      implement this review process. We reviewed the literature on the development of
      recording and reviewing neonatal resuscitation and have summarised the ethical
      concerns involved. Recording and reviewing vital physiological parameters and
      video imaging of neonatal resuscitation in the delivery room is a valuable tool
      for quality assurance, education and research. Furthermore, it can improve the
      quality of neonatal resuscitation provided. We observed that ethical dilemmas
      arise as the review process is operating in several domains of healthcare that
      all have their specific moral framework with requirements and conditions on
      issues such as consent, privacy and data storage. These moral requirements and
      conditions vary due to local circumstances. Further research on the ethical
      aspects of recording and reviewing is desirable before wider implementation of
      this technique can be recommended.

PMID- 29353258
TI  - Aplasia cutis congenita and 'vanishing twin' caused by iatrogenic fetal
      reduction.

PMID- 29353259
TI  - Non-invasive prenatal testing of pregnancies at risk for phenylketonuria.
AB  - BACKGROUND: Phenylketonuria (PKU) is a common metabolic disorder caused
      predominately by mutations in the phenylalanine hydroxylase (PAH) gene. The aim
      of the study was to design and validate the performance of a non-invasive
      prenatal test (NIPT) for PKU using circulating single molecule amplification and
      resequencing technology (cSMART). METHODS: A total of 18 couples at genetic risk
      for having a child with PKU were recruited to the study. Gold standard invasive
      prenatal diagnosis (IPD) was performed on amniocyte or villus cell DNA by Sanger
      sequencing, targeting the known parental PAH mutations. Retrospectively, NIPT was
      also performed on stored maternal plasma samples from the 18 pregnancies by a
      multiplex cSMART assay designed to target all known DNA variants in the PAH gene.
      RESULTS: Benchmarking against IPD results, NIPT correctly genotyped all fetuses,
      including six compound heterozygotes with PKU, four normal non-carriers of PKU
      and eight heterozygote carriers of PKU comprising five cases of a maternally
      inherited mutation and three cases of a paternally inherited mutation.
      CONCLUSIONS: The NIPT cSMART PKU assay was highly sensitive and specific for
      mutation detection and correct assignment of fetal genotypes. Based on
      comprehensive mutation coverage across the PAH gene, the assay may initially have
      clinical utility as a pregnancy screening test for high-risk carrier couples.

PMID- 29353260
TI  - Wide variation in severe neonatal morbidity among very preterm infants in
      European regions.
AB  - OBJECTIVE: To investigate the variation in severe neonatal morbidity among very
      preterm (VPT) infants across European regions and whether morbidity rates are
      higher in regions with low compared with high mortality rates. DESIGN: Area-based
      cohort study of all births before 32 weeks of gestational age. SETTING: 16
      regions in 11 European countries in 2011/2012. PATIENTS: Survivors to discharge
      from neonatal care (n=6422). MAIN OUTCOME MEASURES: Severe neonatal morbidity was
      defined as intraventricular haemorrhage grades III and IV, cystic periventricular
      leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity
      grades >=3. A secondary outcome included severe bronchopulmonary dysplasia (BPD),
      data available in 14 regions. Common definitions for neonatal morbidities were
      established before data abstraction from medical records. Regional severe
      neonatal morbidity rates were correlated with regional in-hospital mortality
      rates for live births after adjustment on maternal and neonatal characteristics.
      RESULTS: 10.6% of survivors had a severe neonatal morbidity without severe BPD
      (regional range 6.4%-23.5%) and 13.8% including severe BPD (regional range 10.0%
      23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%-18.8%).
      Differences between regions remained significant after consideration of maternal
      and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were
      not correlated with mortality rates (P=0.50). CONCLUSION: Severe neonatal
      morbidity rates for VPT survivors varied widely across European regions and were
      independent of mortality rates.

PMID- 29353261
TI  - Impact of delivered tidal volume on the occurrence of intraventricular
      haemorrhage in preterm infants during positive pressure ventilation in the
      delivery room.
AB  - BACKGROUND AND OBJECTIVES: Delivery of inadvertent high tidal volume (VT) during
      positive pressure ventilation (PPV) in the delivery room is common. High VT
      delivery during PPV has been associated with haemodynamic brain injury in animal
      models. We examined if VT delivery during PPV at birth is associated with brain
      injury in preterm infants <29 weeks' gestation. METHODS: A flow-sensor was placed
      between the mask and the ventilation device. VT values were compared with
      recently described reference ranges for VT in spontaneously breathing preterm
      infants at birth. Infants were divided into two groups: VT<6  mL/kg or VT>6 mL/kg
      (normal and high VT, respectively). Brain injury (eg, intraventricular
      haemorrhage (IVH)) was assessed using routine ultrasound imaging within the first
      days after birth. RESULTS: A total of 165 preterm infants were included, 124
      (75%) had high VT and 41 (25%) normal VT. The mean (SD) gestational age and birth
      weight in high and normal VT group was similar, 26 (2) and 26 (1) weeks, 858
      (251) g and 915 (250) g, respectively. IVH in the high VT group was diagnosed in
      63 (51%) infants compared with 5 (13%) infants in the normal VT group
      (P=0.008).Severe IVH (grade III or IV) developed in 33/124 (27%) infants in the
      high VT group and 2/41 (6%) in the normal VT group (P=0.01). CONCLUSIONS: High VT
      delivery during mask PPV at birth was associated with brain injury. Strategies to
      limit VT delivery during mask PPV should be used to prevent high VT delivery.

PMID- 29353262
TI  - Preterm human milk macronutrient concentration is independent of gestational age
      at birth.
AB  - OBJECTIVE: To evaluate the amount of macronutrients in aggregate of human milk
      samples after preterm delivery during the first 2 months of lactation. METHODS:
      Analysis of the donated single milk samples, gained by complete emptying of the
      whole breast at the same daytime between 24+0 and 35+6 gestational age (GA), was
      designed as prospective observational cohort trial. Two milk samples were
      analysed every postnatal week up to the discharge from the hospital, week 9 or
      loss of lactation. 24-Hour milk collection was not done. Analysis was performed
      using the MIRIS Human Milk Analyser (MIRIS AB, Uppsala, Sweden). RESULTS: A set
      of 1917 human milk samples donated by 225 mothers after preterm labour was
      analysed. Group A (24-30 GA) contains 969 milk samples; group B (31-35 GA)
      contains 948 milk samples. No difference in milk composition between the groups
      was identified. Median of true protein content decreased from 1.6 g/dL in group A
      and 1.5 g/dL in group B in the first week of life, to 1.1 g/dL in both groups at
      the end of week 3, and then remained stable up to week 9. Content of
      carbohydrates and fat was stable during the whole observation, with
      interindividual differences. CONCLUSION: Human milk does not differ as a function
      of degree of prematurity. Protein content of preterm human milk is low and
      decreases during the first 3 weeks of lactation. Recommended daily protein intake
      cannot be achieved with routine fortification in majority of milk samples.

PMID- 29353263
TI  - Subcutaneous adipose tissue biology in metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a common global problem that comprises the cardio
      metabolic cluster and predisposes to both diabetes and cardiovascular diseases.
      Although the pathogenic mechanisms have not been elucidated, both increased
      inflammation and insulin resistance play a pivotal role. It appears that both
      monocyte/macrophages and adipose tissue (AT) conspire to accentuate both the pro
      inflammatory state and increased insulin resistance. Whilst there are scant data
      on visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) biology,
      there are data on subcutaneous adipose tissue (SAT) dysregulation. There is a
      significant increase in macrophages and crown-like structures in the SAT of
      patients with MetS. With respect to adipokines, there is an increase in plasma
      leptin, plasminogen activator inhibitor-1, retinol-binding protein-4 (RBP-4),
      chemerin, serum amyloid-A, C-reactive protein (CRP), interleukin-1, -6, -8,
      lipopolysaccharide, fetuin A (FetA) and a decrease in adiponectin and omentin-1.
      All of the abnormalities in plasma were also confirmed for SAT-secreted
      adipokines except for adiponectin and RBP-4 which derive largely from VAT. As
      many of these biomediators correlate with both insulin resistance and increased
      inflammation, we can posit that dysregulation of SAT is detrimental and
      contributes to both the pathogenesis of MetS and its sequalae. Furthermore, as
      future directions, much work is needed with respect to VAT/EAT biology,
      autophagy, sirtuins, the gut microbiome, browning of AT, to further elucidate
      this common syndrome and identify potential therapeutic targets to forestall its
      serious complications.

PMID- 29353264
TI  - Response to growth hormone treatment in very young patients with growth hormone
      deficiencies and mini-puberty.
AB  - BACKGROUND: The aim of the study was to assess the response to growth hormone
      (GH) treatment in very young patients with GH deficiency (GHD) through a
      national, multi-center study. Possible factors affecting growth response were
      assessed (especially mini-puberty). METHODS: Medical reports of GHD patients in
      whom treatment was initiated between 0 and 3 years of age were retrospectively
      evaluated. RESULTS: The cohort numbered 67. The diagnosis age was 12.4+/-8.6
      months, peak GH stimulation test response (at diagnosis) as 1.0+/-1.4 ng/mL. The
      first and second years length gain was 15.0+/-4.3 and 10.4+/-3.4 cm. Weight gain
      had the largest effect on first year growth response; whereas weight gain and GH
      dose were both important factors affecting second year growth response. In the
      multiple pituitary hormone deficiency (MPHD) group (n=50), first year GH response
      was significantly greater than in the isolated GH deficiency (IGHD) group (n=17)
      (p=0.030). In addition first year growth response of infants starting GH between
      0 and 12 months of age (n=24) was significantly greater than those who started
      treatment between 12 and 36 months of age (n=43) (p<0.001). These differences
      were not seen in the second year. Delta Length/height standard deviation score
      (SDS), Delta body weight SDS, length/height SDS, weight SDS in MPHD without
      hypogonadism for the first year of the GH treatment were found as significantly
      better than MPHD with hypogonadism. CONCLUSIONS: Early onsets of GH treatment,
      good weight gain in the first year of the treatment and good weight gain-GH dose
      in the second year of the treatment are the factors that have the greatest effect
      on length gain in early onset GHD. The presence of the sex steroid hormones
      during minipubertal period influence growth pattern positively under GH treatment
      (closer to the normal percentage according to age and gender).

PMID- 29353265
TI  - Growth, sexual and bone development in a boy with bilateral anorchia under
      testosterone treatment guided by the development of his monozygotic twin.
AB  - BACKGROUND: Sex steroids are essential for sexual maturation, linear growth and
      bone development. However, there is no consensus on the optimal timing, dosage
      and dosage interval of testosterone therapy to induce pubertal development and
      achieve a normal adult height and bone mass in children with hypogonadism. CASE
      PRESENTATION: A monozygotic monochorial male twin pair, of which one boy was
      diagnosed with anorchia at birth due to testicular regression syndrome was
      followed from the age of 3 until the age of 18 years. Low dose testosterone
      substitution (testosterone esters 25 mg/2 weeks) was initiated in the affected
      twin based on the start of pubertal development in the healthy twin and then
      gradually increased accordingly. Both boys were followed until age 18 and were
      compared as regards to linear growth, sexual maturation, bone maturation and bone
      development. Before puberty induction both boys had a similar weight and height.
      During puberty, a slightly faster weight and height gain was observed in the
      affected twin. Both boys ended up however, with a similar and normal (near) adult
      height and weight and experienced a normal development of secondary sex
      characteristics. At the age of 17 and 18 years, bone mineral density, body
      composition and volumetric bone parameters at the forearm and calf were evaluated
      in both boys. The affected boy had a higher lean mass and muscle cross-sectional
      area. The bone mineral density at the lumbar spine and whole body was similar.
      Trabecular and cortical volumetric bone parameters were comparable. At one
      cortical site (proximal radius), however, the affected twin had a smaller
      periosteal and endosteal circumference with a thicker cortex. CONCLUSIONS: In
      conclusion, a low dose testosterone substitution in bilateral anorchia led to a
      normal onset of pubertal development and (near) adult height. Furthermore, there
      was no difference in bone mineral density at the age of 17 and 18 years.

PMID- 29353266
TI  - Twenty-seven mutations with three novel pathologenic variants causing biotinidase
      deficiency: a report of 203 patients from the southeastern part of Turkey.
AB  - BACKGROUND: Biotinidase deficiency (BD) is an autosomal recessive inborn error of
      metabolism characterized by neurologic and cutaneous symptoms and can be detected
      by newborn screening. Newborn screening for BD was implemented in Turkey at the
      end of 2008. METHODS: In total, 203 patients who were identified among the
      infants detected by the newborn screening were later confirmed to have BD through
      measurement of serum biotinidase activity. We also performed BTD mutation
      analysis to characterize the genetic profile. RESULTS: Twenty-seven mutations
      were identified. The most commonly found variants were c.1330G>C (p.D444H),
      c.1595C>T (p.T532M), c.470G>A (p.R157H), and c.198_104delGCGGCTGinsTCC (p.C33Ffs
      ) with allele frequencies of 0.387, 0.175, 0.165 and 0.049, respectively. Three
      novel pathogenic and likely pathogenic variants were identified: p.W140*
      (c.419G>A), p.S319F (c.956C>T) and p.L69Hfs*24 (c.192_193insCATC). We also
      identified three mutations reported in just one patient in the past (p.V442Sfs*59
      [c.1324delG], p.H447R [c.1340A>G] and p.198delV [c.592_594delGTC]). Although all
      of the patients were asymptomatic under the treatment of biotin, only one
      patient, who had the novel c.419G>A homozygous mutation became symptomatic during
      an episode of acute gastroenteritis with a presentation of ketosis and metabolic
      acidosis. Among the screened patients, 156 had partial and 47 had profound BD.
      CONCLUSIONS: We determined the mutation spectra of BD from the southeastern part
      of Turkey. The results of this study add three more mutations to the total number
      of mutations described as causing BD.

PMID- 29353267
TI  - Bioactive pyrrole alkaloids isolated from the Red Sea: marine sponge Stylissa
      carteri.
AB  - Fifteen pyrrole alkaloids were isolated from the Red Sea marine sponge Stylissa
      carteri and investigated for their biological activities. Four of them were
      dibrominated [(+) dibromophakelline, Z-3-bromohymenialdisine, (+/-) ageliferin
      and 3,4-dibromo-1H-pyrrole-2-carbamide], nine compounds were monobrominated [(-)
      clathramide C, agelongine, (+) manzacidin A, (-) 3-bromomanzacidin D, Z
      spongiacidin D, Z-hymenialdisine, 2-debromostevensine, 2-bromoaldisine and 4
      bromo-1H-pyrrole-2-carbamide)] and finally, two compounds were non-brominated
      derivatives viz., E-debromohymenialdisine and aldisine. The structure
      elucidations of isolated compounds were based on 1D & 2D NMR spectroscopic and MS
      studies, as well as by comparison with literature. In-vitro, Z-spongiacidin D
      exhibited a moderate activity on (ARK5, CDK2-CycA, CDK4/CycD1, VEGF-R2, SAK and
      PDGFR-beta) protein kinases. Moreover, Z-3-bromohymenialdisine showed nearly
      similar pattern. Furthermore, Z-hymenialdisine displayed a moderate effect on
      (ARK5 & VEGF-R2) and (-) clathramide C showed a moderate activity on AURORA-A
      protein kinases. While, agelongine, (+) manzacidin A, E-debromohymenialdisine and
      3,4-dibromo-1H-pyrrole-2-carbamide demonstrated only marginal inhibitory
      activities. The cytotoxicity study was evaluated in two different cell lines. The
      most effective secondary metabolites were (+) dibromophakelline and Z-3
      bromohymenialdisine on L5178Y. Finally, Z-hymenialdisine, Z-3-bromohymenialdisine
      and (+/-) ageliferin exhibited the highest cytotoxic activity on HCT116. No
      report about inhibition of AURORA-A and B by hymenialdisine/hymenialdisine
      analogs existed and no reported toxicity of ageliferin existed in literature.

PMID- 29353268
TI  - Non-Invasive Diagnostic Criteria for Hepatocellular Carcinoma in Hepatitis B
      Virus-Endemic Areas: Is Cirrhosis Indispensable?
AB  - AIM: To confirm whether cirrhosis is indispensable for the non-invasive
      diagnostic criteria for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)
      endemic areas. METHODS: Between January 2014 and December 2014, a total of 409
      patients with pathologically proven focal liver lesions who underwent contrast
      enhanced ultrasound (CEUS) were recruited from our institution. Clinical liver
      cirrhosis, HBV/HCV infection and HCC-typical vascular pattern of the targeted
      lesion on CEUS were evaluated. The following 3 criteria were applied to these
      patients to diagnose HCC: criterion 1, clinical liver cirrhosis and HCC-typical
      vascular pattern; criterion 2, HBV/HCV infection and HCC-typical vascular
      pattern; criterion 3, HBV/HCV infection or clinical liver cirrhosis and HCC
      typical vascular pattern. Pathological reports were considered the gold standard.
      RESULTS: A total of 311 patients had confirmed HCC by pathology. The sensitivity,
      specificity, accuracy, positive predictive value, negative predictive value and
      area under the ROC curve for criterion 1 were 29.6, 90.8, 44.3, 91.1, 28.9, and
      0.60% respectively. For criterion 2, they were 83.3, 74.5, 81.2, 91.2, 58.4, and
      0.79%, respectively, and for criterion 3, they were 86.2, 72.5, 82.9, 90.9, 62.3,
      and 0.79% respectively. CONCLUSIONS: In HBV-endemic areas, when using the HBV/HCV
      infection instead of cirrhosis as the precondition of the non-invasive diagnostic
      criteria for HCC, we should be aware of the potential false positive. Cirrhosis
      still plays an important role in the non-invasive diagnostic criteria for HCC
      because of the high specificity.

PMID- 29353270
TI  - Screening for Brain Involvement in Infants with Multifocal Cutaneous Infantile
      Hemangiomas.
AB  - BACKGROUND: Multifocal (>=5) infantile hemangiomas (IHs) are known as a risk
      factor for extracutaneous involvement. Liver is the most commonly involved organ,
      but involvement of other systems has also been reported. This study aims to
      describe the characteristic findings in a group of infants with multiple
      cutaneous hemangiomas, with emphasis on intracranial involvement. METHODS: A
      retrospective case series study was carried out in a pediatric dermatology unit
      of a tertiary pediatric medical center. Patients diagnosed with multiple
      cutaneous IHs from 2006 to 2015 were identified by a computerized search.
      Clinical data were retrieved from the medical charts. RESULTS: A total of 60
      infants (37 females and 23 males) were identified for analysis. Forty-four brain
      ultrasounds were recorded and reported as normal. One patient out of the 44 was
      later diagnosed with a small asymptomatic hemangioma seen on a brain MRI/MRA done
      for another indication. CONCLUSION: Brain hemangiomas may present as an
      asymptomatic incidental finding in infants presenting with multifocal cutaneous
      and liver IHs. The single case reported in our study emphasizes the low
      prevalence and the benign course expected. Therefore, routine ultrasound
      screening for brain involvement is probably unnecessary for this population.

PMID- 29353269
TI  - Clinical Characteristics and Allergen Sensitization Patterns of Patients with
      Local Allergic Rhinitis in Southern China.
AB  - BACKGROUND: Local allergic rhinitis (LAR) is characterized by the production of
      specific IgE (sIgE) in the nasal mucosa without evidence of systemic atopy. The
      characteristics of LAR in Caucasians have been well documented. LAR is
      understudied in China, with prevalence, patient demographics, symptomatology, and
      the allergen sensitization profile being poorly understood. The purpose of this
      study is to investigate the demographics, characteristics, and allergen
      sensitization profile of patients with LAR in Southern China. METHODS: A total of
      194 patients with rhinitis and 13 healthy subjects were enrolled in the current
      study. The patients' demographic data, clinical history, and symptoms were
      recorded. Local and systemic sIgE to a wide panel of specific allergens were
      measured in the nasal secretion and serum samples. RESULTS: Among the rhinitis
      patients, 115 were classified as allergic rhinitis (AR; 59.3%), 15 as LAR (7.7%),
      and 64 as non-AR (33.0%). The demographic characteristics, duration, frequency,
      and severity of symptoms were similar, although LAR exhibited higher symptom
      scores for nasal itch. Monosensitization was the predominant pattern of
      sensitization in both AR (109 out of 115, 95%) and LAR (14 out of 15, 93%). House
      dust mite was the dominant allergen in AR patients (109 out of 115, 95%), while
      pollen was the dominant allergen in LAR patients (11 out of 15, 73%). CONCLUSION:
      The prevalence of LAR patients in Southern China was 7.7%. Pollen was the most
      common sensitizing allergen for the local LAR patients, which differs from
      Caucasian studies, in which house dust mite was the dominant sensitizing
      allergen. Monosensitization was the predominant pattern in both AR and LAR.

PMID- 29353271
TI  - Erythrocytes and Skeletal Muscle Unsaturated and Omega-6 Fatty Acids Are
      Positively Correlated after Caloric Restriction and Exercise.
AB  - BACKGROUND: Nutritional intervention studies with fatty acid (FA) supplements
      assess the efficacy of the intervention by measuring the changes in erythrocyte
      membrane lipid profiles reflected in tissue composition changes. The aim was to
      determine the effects of caloric restriction (CR) on erythrocytes lipid
      composition and to compare and correlate these changes with skeletal muscle acid
      profiles after CR. METHODS: Erythrocytes were obtained from 11 healthy men before
      and after 4 weeks of 33% CR in post-exercise conditions; muscle biopsies were
      obtained from the same athletes after 4 weeks of 33% CR in post-exercise
      conditions. Samples were used for FA determination by chromatography. RESULTS: CR
      significantly modified erythrocyte FAs composition. Skeletal muscle FA profile
      was significantly different from that for the erythrocytes. The erythrocyte FA
      profile was more saturated (52.1 +/- 1.5% and 32.8 +/- 0.9%, respectively) and
      less monounsaturated (21.0 +/- 0.8% and 39.0 +/- 2.0%, respectively) than the
      skeletal muscle FA profile and similarly polyunsaturated. CONCLUSIONS: CR
      modifies erythrocyte lipid composition, mainly omega-6 FAs. Erythrocyte
      monounsaturated, polyunsaturated and omega-6 FAs, but not the saturated and omega
      3 FAs, were significantly positively correlated with skeletal muscle FAs. There
      is a discordance between saturated and omega-3 FAs from erythrocyte and from
      muscle, but monounsaturated, polyunsaturated and omega-6 fatty acids are
      positively correlated.

PMID- 29353272
TI  - Optical Coherence Tomography Angiography Offers New Insights into
      Choriocapillaris Perfusion.
AB  - The choriocapillaris (CC) represents a fundamentally important vascular layer
      that is subject to physiologic changes with increasing age and that is also
      associated with a wide range of chorioretinal diseases. So far, information on
      blood flow in this specific layer has remained limited. With the advent of
      optical coherence tomography angiography (OCTA), new perspectives and
      possibilities of CC imaging have begun to evolve. This article shall review the
      opportunities and challenges of applying OCTA technology to the CC layer and
      summarize the current clinical efforts in OCTA CC imaging exemplarily in dry age
      related macular degeneration and central serous chorioretinopathy.

PMID- 29353273
TI  - Metabolomics in Sepsis and Its Impact on Public Health.
AB  - Sepsis, with its often devastating consequences for patients and their families,
      remains a major public health concern that poses an increasing financial burden.
      Early resuscitation together with the elucidation of the biological pathways and
      pathophysiological mechanisms with the use of "-omics" technologies have started
      changing the clinical and research landscape in sepsis. Metabolomics (i.e., the
      study of the metabolome), an "-omics" technology further down in the "-omics"
      cascade between the genome and the phenome, could be particularly fruitful in
      sepsis research with the potential to alter the clinical practice. Apart from its
      benefit for the individual patient, metabolomics has an impact on public health
      that extends beyond its applications in medicine. In this review, we present
      recent developments in metabolomics research in sepsis, with a focus on
      pneumonia, and we discuss the impact of metabolomics on public health, with a
      focus on free/libre open source software.

PMID- 29353274
TI  - Postoperative Immobilization following Occipitocervical Fusion in the Pediatric
      Population: Outcome Evaluation and Review of Literature.
AB  - The scientific literature does not have a consensus about the role and method of
      postoperative immobilization after occipitocervical fusion in the pediatric
      population. The primary goal of this study is to review the medical literature
      and evaluate different immobilization methods and their impact on fusion,
      following the surgical management of craniocervical instability in children. It
      started with an extensive research of randomized controlled trials, series of
      cases and case reports, describing occipitocervical junction pathologies,
      clinical, epidemiological characteristics, and treatment. The search was
      performed using the Pubmed database evaluating all the literature involving
      postoperative immobilization after occipitocervical fusion in pediatric patients.
      The results showed that most cases of occipitocervical stabilization were due to
      congenital spinal instability followed by trauma in most series. The most common
      type of surgery performed was occipitocervical fusion using screw and rod
      constructs. The different methods of postoperative immobilization did not affect
      outcomes. Then, we can conclude that screw-and-rod constructions in
      occipitocervical fusion augment the rates of fusion, independently from which
      immobilization was used, even when none was used at all.

PMID- 29353275
TI  - Endocrine and Metabolic Disturbances in Survivors of Hematopoietic Stem Cell
      Transplantation in Childhood and Adolescence.
AB  - BACKGROUND/AIMS: The objective was to evaluate endocrine complications in
      survivors of hematopoietic stem cell transplantation (HSCT) performed during
      childhood. METHODS: Endocrine dysfunction and metabolic syndrome parameters were
      assessed by chart review of 178 childhood HSCT survivors (median age at
      evaluation, 15.5 [range: 3.8-29.8] years; median follow-up, 8.5 [range: 2-23.4]
      years). RESULTS: The following statistically significant associations were
      identified (p < 0.05 for all): growth hormone deficiency (17.4%) was associated
      with cranial/craniospinal irradiation, total body irradiation (TBI), allogeneic
      HSCT, and longer follow-up. Short adult stature (23.3% of patients who had
      attained adult height) was associated with cranial/craniospinal irradiation and,
      in females, with younger age at HSCT. Primary gonadal failure was more prevalent
      in females (52.6 vs. 24.1%), and was associated with TBI in males and with a
      primary diagnosis of hematological malignancy in females. Hypothyroidism (25.2%)
      was associated with previous neck/mediastinal irradiation. Metabolic disturbances
      included obesity (3.9%), type 2 diabetes (2.2%), impaired glucose tolerance
      (2.8%), and dyslipidemia (18.5%). Dyslipidemia was associated with a primary
      diagnosis of hematological malignancy, TBI, and a positive family history of
      dyslipidemia. Endocrine dysfunction was less frequent in patients who had
      received fludarabine. CONCLUSIONS: Patients after HSCT require long-term
      surveillance for the detection of endocrine and metabolic disorders.
      Nonmyeloablative conditioning regimens may reduce the incidence of these
      complications.

PMID- 29353276
TI  - What Can Google Inform Us about People's Interests regarding Dental Caries in
      Different Populations?
AB  - The diagnosis or suspicion of dental caries can lead people to seek additional
      information on the Internet through the use of structured queries in search
      engine tools. This action generates a considerable volume of data, which can be
      analyzed to provide a better understanding of the public's behavior linked to the
      consumption of oral health information. This study aimed to assess the volume and
      profile of web searches on dental caries-related queries performed by Google
      users from different countries. The monthly variation of the Search Volume Index
      (SVI) for dental caries was obtained in Google Trends for the period between
      January 2004 and September 2016. The validity of SVI data was assessed by their
      levels of stability and correlation with the disability-adjusted life-years
      (DALYs) for permanent teeth. In all countries, a trend of an increasing interest
      of Google users in dental caries issues was revealed by the comparison of the
      means observed in the predictive models and those in the last 12 months. The
      interest levels varied throughout the year, with the observation of the highest
      SVI values in the spring and the lowest in the summer. The most popular queries
      were markedly associated with symptoms and treatments, with a little interest in
      prevention. In conclusion, the use of Internet data mining could be helpful in
      establishing the dental needs of specific population groups in a near real-time,
      since the web consumption of dental information is increasing in importance and
      appears to have a direct relation with untreated dental caries.

PMID- 29353277
TI  - A Critical Review of the Consensus Statement from the European Atherosclerosis
      Society Consensus Panel 2017.
AB  - BACKGROUND: The Consensus Statement from the European Atherosclerosis Society
      (EAS) Consensus Panel 2017 concludes on the basis of 3 different types of
      clinical studies that low-density lipoprotein (LDL) causes atherosclerotic
      cardiovascular disease (ASCVD). In Mendelian randomization studies, rare genetic
      mutations affecting LDL receptor function were found to cause higher or lower LDL
      C levels, which are associated with correspondingly altered ASCVD risk. In
      prospective cohort studies and randomized controlled trials (RCTs) of statins, a
      remarkably consistent log-linear association was demonstrated between the
      absolute magnitude of LDL-C exposure and ASCVD risk. The EAS Statement proposes
      that any mechanism of lowering plasma LDL concentration should reduce the risk of
      ASCVD events proportional to the absolute reduction in LDL-C and the cumulative
      duration of exposure to lower LDL-C. However, as we explain, we do not find this
      conclusion acceptable. SUMMARY: Our review points out that different
      interpretations are possible for the results of Mendelian randomization studies.
      As for prospective cohort studies, many inconsistent reports on the association
      of LDL-C and ASCVD were disregarded when drafting the Statement, reports with and
      without genetic factors related to LDL receptor function should be analyzed
      separately, and the term ASCVD in the Statement is used inappropriately because
      myocardial infarction and cerebral infarction differ in their association with
      LDL-C. As for RCTs, clinical reports on statins published before and after the
      implementation of new regulations affecting clinical trials (2004/2005) should
      not both be included in meta-analyses because the evaluated efficacy of statins
      changed markedly, and the irreversible adverse effects of statins need to be
      evaluated more rigorously now that their mechanisms have been elucidated. Key
      Messages: Apart from the EAS hypothesis that LDL causes ASCVD, recent
      pharmacological/biochemical studies, as summarized in this review and elsewhere,
      have revealed that atherosclerosis is caused by statins taken to lower LDL-C, as
      well as by warfarin and some types of vegetable fats and oils, in the absence of
      significantly elevated LDL-C levels. Thus, the promotion of statin treatment by
      the Statement is rather risky and we do not feel that the conclusions are
      justified for the prevention of ASCVD.

PMID- 29353278
TI  - Stereoselective Inhibition of Renal Basolateral Human Organic Anion Transporter 3
      by Lansoprazole Enantiomers.
AB  - Lansoprazole, a proton pump inhibitor, potently inhibits human organic anion
      transporter, hOAT3 (SLC22A8). Lansoprazole has an asymmetric atom in its
      structure and is clinically administered as a racemic mixture of (R)-and (S)
      enantiomers. However, little is known about the stereoselective inhibitory
      potencies of lansoprazole against hOAT3 and its homolog, hOAT1. In the present
      study, the stereoselective inhibitory effect of lansoprazole was evaluated using
      hOAT1-and hOAT3-expressing cultured cells. hOAT1 and hOAT3 transported [14C]p
      aminohippurate and [3H]estrone-3-sulfate (ES) with Michaelis-Menten constants of
      29.8 +/- 4.0 and 30.1 +/- 9.0 umol/L respectively. Lansoprazole enantiomers
      inhibited hOAT1- and hOAT3-mediated transport of each substrate in a
      concentration-dependent manner. The IC50 value of (S)-lansoprazole against hOAT3
      mediated transport of [3H]ES (0.61 +/- 0.08 umol/L) was significantly lower than
      that of (R)-lansoprazole (1.75 +/- 0.31 umol/L). In contrast, stereoselectivity
      was not demonstrated for the inhibition of hOAT1. Furthermore, (S)-lansoprazole
      inhibited hOAT3-mediated transport of pemetrexed and methotrexate (hOAT3
      substrates) more strongly than the corresponding (R)-lansoprazole. This study is
      the first to demonstrate that the stereoselective inhibitory potency of (S)
      lansoprazole against hOAT3 is greater than that of (R)-lansoprazole. The present
      findings provide novel information about the drug interactions associated with
      lansoprazole.

PMID- 29353279
TI  - Lactobacillus rhamnosus GG in Experimental Oral Biofilms Exposed to Different
      Carbohydrate Sources.
AB  - Probiotic administration may favour caries prevention, as recent research has
      shown. This in vitro study aimed to investigate the growth of Lactobacillus
      rhamnosus GG (LGG) in experimental biofilms exposed to various carbohydrates, and
      also to assess its cariogenic potential. Multispecies experimental oral biofilms
      with or without LGG were grown with a sole-carbohydrate source
      (fructose/glucose/lactose/sorbitol/sucrose). The viable cells of LGG and
      structure of the biofilms were examined after 64.5 h of incubation, and pH values
      of spent media were measured at 16.5, 40.5, and 64.5 h. Fermentation profiles of
      LGG in biofilm media were assessed with study carbohydrate as the sole energy
      source. Our results showed that LGG reached higher viable cell numbers with
      glucose and sucrose in 64.5-h multispecies experimental oral biofilms compared to
      other carbohydrates. When LGG was incorporated in biofilms, no distinct pH
      changes at any time points were observed under any of the carbohydrates used; the
      pH values of spent media at each time point were lower when lactose was used,
      compared to other carbohydrates. The fermentation profiles of LGG in biofilm
      media were similar to its growth in MRS (no obvious growth with lactose or
      sucrose). In conclusion, LGG in our in vitro multispecies experimental oral
      biofilms was capable of surviving and growing well in each carbohydrate source.
      LGG might not have harmful effects on dental hard tissues. Another finding from
      our study was that the lowest pH values were observed in the presence of lactose,
      and the thickest biofilms were in sucrose.

PMID- 29353281
TI  - The Effectiveness of Dietary Approaches to Stop Hypertension Diet Intervention in
      Persons with Arterial Hypertension and Obesity: A Key Role of the Patients'
      Personality Profile.
AB  - BACKGROUND/AIMS: Benefits resulting from weight loss and dietary approaches to
      stop hypertension (DASH) diet in the treatment of arterial hypertension led to a
      search for a better therapy that would include psychological factors. The present
      study aimed to assess the relationship between the personality traits included in
      the Big Five personality traits and the effectiveness of treatment for weight
      loss in patients with essential hypertension and excessive body weight. METHODS:
      The study involved 84 patients with essential hypertension, overweight or
      obesity, managed by a hypertensiologist. All patients underwent a 3-month diet
      treatment as part of the development process of an individualised eating plan
      that follows the principles of DASH diet and food education. Body mass index and
      DASH index were calculated before and after the therapy. NEO Five-Factor
      Inventory was applied to measure psychological variables. RESULTS: The
      intervention led to a statistically significant increase of DASH index measured
      before and after treatment. There was a significant correlation between the
      increase of DASH index and gender. Patients presented higher intensity of
      openness to experience, extraversion, conscientiousness and lower levels of
      neuroticism and agreeableness compared to general population. CONCLUSION: The
      influence of psychological variables on the observed difference between men and
      women in DASH values and weight loss was not demonstrated.

PMID- 29353280
TI  - Microstructure of Strategic White Matter Tracts and Cognition in Memory Clinic
      Patients with Vascular Brain Injury.
AB  - BACKGROUND: White matter injury is an important factor for cognitive impairment
      in memory clinic patients. We determined the added value of diffusion tensor
      imaging (DTI) of strategic white matter tracts in explaining variance in
      cognition in memory clinic patients with vascular brain injury. METHODS: We
      included 159 patients. Conventional MRI markers (white matter hyperintensity
      volume, lacunes, nonlacunar infarcts, brain atrophy, and microbleeds), and
      fractional anisotropy and mean diffusivity (MD) of the whole brain white matter
      and of 18 white matter tracts were related to cognition using linear regression
      and Bayesian network analysis. RESULTS: On top of all conventional MRI markers
      combined, MD of the whole brain white matter explained an additional 3.4% (p =
      0.014), 7.8% (p < 0.001), and 1.2% (p = 0.119) variance in executive functioning,
      speed, and memory, respectively. The Bayesian analyses of regional DTI measures
      identified strategic tracts for executive functioning (right superior
      longitudinal fasciculus), speed (left corticospinal tract), and memory (left
      uncinate fasciculus). MD within these tracts explained an additional 3.4% (p =
      0.012), 3.8% (p = 0.007), and 2.1% (p = 0.041) variance in executive functioning,
      speed, and memory, respectively, on top of all conventional MRI and global DTI
      markers combined. CONCLUSION: In memory clinic patients with vascular brain
      injury, DTI of strategic white matter tracts has a significant added value in
      explaining variance in cognitive functioning.

PMID- 29353282
TI  - Differential Changes in Myocardial Performance Index and Its Time Intervals in
      Donors and Recipients of Twin-to-Twin Transfusion Syndrome before and after Laser
      Therapy.
AB  - OBJECTIVE: To evaluate left myocardial performance index (MPI) and time intervals
      in fetuses with twin-to-twin transfusion syndrome (TTTS) before and after laser
      surgery. METHODS: Fifty-one fetal pairs with TTTS and 47 uncomplicated
      monochorionic twin pairs were included. Left ventricular isovolumetric
      contraction time (ICT), ejection time (ET), and isovolumetric relaxation time
      (IRT) were measured using conventional Doppler. RESULTS: Recipients showed
      prolonged ICT (46 +/- 12 vs. 31 +/- 8 vs. 30 +/- 5 ms; p < 0.001) and IRT (51 +/-
      9 vs. 43 +/- 8 vs. 43 +/- 5 ms; p < 0.001) and higher MPI (0.57 +/- 0.12 vs. 0.47
      +/- 0.09 vs. 0.44 +/- 0.05; p < 0.001) than donors and controls. Donors showed
      shorter ET than recipients and controls (157 +/- 12 vs. 169 +/- 10 vs. 168 +/- 10
      ms; p < 0.001) and higher MPI than controls (0.47 +/- 0.09 vs. 0.44 +/- 0.05; p =
      0.006). Preoperative MPI changes were observed in all TTTS stages. Time intervals
      partially improved after surgery. CONCLUSION: Donor and recipient twins had
      higher MPI due to different changes in the time intervals, possibly reflecting
      the state of hypovolemia in the donor and hypervolemia and pressure overload in
      the recipient.

PMID- 29353284
TI  - Usefulness of Totally Implantable Central Venous Access Devices in Elderly
      Patients: A Retrospective Study.
AB  - BACKGROUND/AIMS: The need for totally implantable central venous access devices
      (TICVADs) has increased with increased opportunities in the use of chemotherapy
      and parenteral nutrition. This study aimed to determine the outcomes of TICVAD
      implantation and use in patients aged >=85 years. METHODS: Between January 2010
      and August 2016, 117 patients underwent TICVAD implantation and their records
      were retrospectively reviewed. RESULTS: Participants were divided into 2 groups
      (plus-85 and sub-85 groups). Fifty-five patients (47.0%) had solid organ cancer
      alone; 35 patients (29.9%) had cerebrovascular or cranial nerve disease. The
      average follow-up period was 201 (2-1,620) days. Major complications were
      identified in 6 (14.6%) plus-85 patients and 11 (14.5%) sub-85 patients (p =
      0.9813). Catheter-related infections developed in 3 plus-85 (7.3%) and 4 sub-85
      patients (5.3%; p = 0.6549). There were no significant group differences in
      hematoma, pneumothorax, occlusion, and removal rates. In plus-85 patients
      examined just before surgery and a month after surgery, increased rates of serum
      albumin and Onodera's prognostic nutritional index were observed in 48% (14/39)
      and 41% (12/39), respectively. CONCLUSIONS: The use of TICVADs in the plus-85
      group resulted in effective outcomes. The results of this retrospective study
      support the wider use of TICVADs in patients aged >=85 years.

PMID- 29353283
TI  - Association between Dental Caries and BMI in Children: A Systematic Review and
      Meta-Analysis.
AB  - Research on the association between dental caries and body mass index (BMI) in
      children has shown contradictory results; thus we aimed to examine the
      association between dental caries and the full range of BMI classes among
      children. We comprehensively searched PubMed, Embase, and the Cochrane Library
      for studies published prior to March 2017. Articles comparing dental caries among
      the full range of BMI classes for children below 18 years of both genders were
      included. Fourteen studies were eligible for this study. Basic information -
      i.e., first author, published year, study design, country, sample size, age, type
      of dental caries index and BMI, main results and conclusions, and means and
      standard deviations of the dental caries indexes used - was pooled. The weighted
      mean differences and corresponding 95% confidence intervals for dental caries
      between children with abnormal weight and those with normal weight were analyzed.
      Generally, no significant differences in caries were found between any abnormal
      weight group and the normal-weight group for both primary and permanent teeth.
      Sensitivity analyses showed that the obese group had more caries than the normal
      weight group in their primary teeth. Significantly more caries was found among
      the overweight and obese children in both primary and permanent teeth in high
      income countries, but not in low- and middle-income countries. We recommend that
      further studies use suitable sample sizes, unify the criteria for BMI
      categorization and the dental caries index, and investigate the confounding
      factors that might influence dental caries and BMI.

PMID- 29353285
TI  - Laser Scanning Microscopic Investigations of the Decontamination of Soot
      Nanoparticles from the Skin.
AB  - BACKGROUND/AIMS: Airborne pollutants, such as nano-sized soot particles, are
      increasingly being released into the environment as a result of growing
      population densities and industrialization. They can absorb organic and metal
      compounds with potential biological activity, such as polycyclic aromatic
      hydrocarbons and airborne pollen allergens. Local and systemic toxicities may be
      induced in the skin if the particulates release their harmful components upon
      dermal contact. METHODS: In the present study, skin pretreatments with serum
      and/or shield as barrier formulations prior to exposure and washing with a
      cleanser subsequent to exposure were evaluated as a protection and
      decontamination strategy using laser scanning microscopy. RESULTS: The results
      indicate that while the application of serum and a cleanser was insufficient for
      decontamination, the pretreatment with shield prior to nanoparticle exposure
      followed by washing led to the removal of a considerable amount of the carbon
      black particles. The combined application of serum and shield before the
      administration of carbon black particles and subsequent washing led to their
      elimination from the skin samples. CONCLUSION: The application of barrier
      enhancing formulations in combination with a cleanser may reduce the penetration
      of harmful airborne particulates by preventing their adhesion to the skin and
      facilitating their removal by subsequent washing with the cleanser.

PMID- 29353286
TI  - Predictors of Thrombocytopenia after Self-Expandable Transcatheter Aortic Valve
      Replacement: A Single-Center Experience from China.
AB  - OBJECTIVES: The importance of thrombocytopenia (TP) has been discussed
      previously. However, data are still limited, especially on predictors of TP. We
      sought to investigate predictors of TP after transcatheter aortic valve
      replacement (TAVR), in particular, clinically significant TP. METHODS: We
      reviewed a total of 123 consecutive patients undergoing TAVR in our medical
      center. They were stratified into 3 groups according to the nadir platelet count
      post-TAVR: no/mild TP, moderate TP, and severe TP. Clinically significant TP,
      also known as major TP, was defined as moderate-to-severe TP (a nadir platelet
      count <100 * 109/L and a >50% decrease in platelet count). RESULTS: Baseline
      platelet, baseline hemoglobin, general anesthesia (GA), valve malpositioning and
      post-TAVR left ventricular ejection fraction were found to be predictors of post
      TAVR nadir platelet count. Major TP was associated with a higher risk of major
      bleeding (OR 3.524, 95% CI 1.546-8.031) and 1-month mortality (OR 11.226, 95% CI
      1.208-104.328). Age (OR 1.110, 95% CI 1.014-1.215) and GA (OR 6.494, 95% CI 2.058
      20.408) were predictors of major TP. CONCLUSION: Post-TAVR nadir platelet count
      can be predicted based on baseline and procedural data. Old age and GA contribute
      to clinically significant TP.

PMID- 29353287
TI  - High CXC Chemokine Ligand 16 (CXCL16) Expression Promotes Proliferation and
      Metastasis of Lung Cancer via Regulating the NF-kappaB Pathway.
AB  - BACKGROUND CXC chemokine ligand 16 (CXCL16) is a soluble chemokine with a
      transmembrane domain, playing an important role in inflammatory regulation. NF
      kappaB has a critical role in tumor progression. Recent studies focused on the
      effect of CXCL16 on tumor progression. However, few reports showed the influence
      of CXCL16 on lung cancer, especially in regulating NF-kappaB activity. Here we
      investigated CXCL16 expression and its clinical significance in lung cancer, as
      well as the effect on lung cancer cell biological characteristics by regulating
      NF-kappaB. MATERIAL AND METHODS CXCL16 expression in lung cancer was detected and
      its associations with clinical characteristics were analyzed. Proliferation and
      invasion of A549 and PC-9 cells was measured before and after silencing CXCL16 or
      inhibiting the NF-kappaB pathway, separately. RESULTS The positive rate of CXCL16
      in lung cancer tissue was significantly higher than that in adjacent tissue, and
      that in patients with lymphatic metastasis was significantly higher than that in
      patients without (all, P<0.05). The positive rate of CXCL16 was significantly
      (P<0.05) positively corrected with poor prognosis of lung cancer. Silencing
      CXCL16 not only suppressed proliferation and invasion of A549 and PC-9 cells, but
      also significantly (P<0.05) inhibited c-Rel, p105, and Rel-B in the NF-kappaB
      pathway. Inhibiting NF-kappaB also suppressed proliferation and invasion of A549
      and PC-9 cells, which was similar to the results after silencing CXCL16.
      CONCLUSIONS Enhanced CXCL16 expression in lung cancer tissue promoted the
      proliferation and invasion of lung cancer cells. CXCL16 might promote
      proliferation and invasion of lung cancer by regulating the NF-kappaB pathway.

PMID- 29353288
TI  - Quercetin Inhibits Breast Cancer Stem Cells via Downregulation of Aldehyde
      Dehydrogenase 1A1 (ALDH1A1), Chemokine Receptor Type 4 (CXCR4), Mucin 1 (MUC1),
      and Epithelial Cell Adhesion Molecule (EpCAM).
AB  - BACKGROUND Quercetin, nature's most common flavonoid, possesses anticarcinogenic
      properties against various forms of cancer. The aim of this study was to
      investigate the effect of quercetin on breast cancer stem cells in the MDA-MB-231
      cell line, and to elucidate the possible mechanisms for those effects. MATERIAL
      AND METHODS We evaluated breast cancer stem cell proliferation, clone generation,
      and mammosphere formation to determine the effect of quercetin treatment on
      breast cancer stem cells. RESULTS In our study, quercetin suppressed breast
      cancer stem cell proliferation, self-renewal, and invasiveness. It also lowered
      the expression levels of proteins related to tumorigenesis and cancer
      progression, such as aldehyde dehydrogenase 1A1, C-X-C chemokine receptor type 4,
      mucin 1, and epithelial cell adhesion molecules. CONCLUSIONS These results
      indicate that quercetin targets and destroys breast cancer stem cells, making it
      a potential novel drug in the fight against cancer.

PMID- 29353289
TI  - The new agreement of the international RIGA consensus conference on nasal airway
      function tests.
AB  - The report reflects an agreement based on the consensus conference of the
      International Standardization Committee on the Objective Assessment of the Nasal
      Airway in Riga, 2nd Nov. 2016. The aim of the conference was to address the
      existing nasal airway function tests and to take into account physical,
      mathematical and technical correctness as a base of international standardization
      as well as the requirements of the Council Directive 93/42/EEC of 14 June 1993
      concerning medical devices. Rhinomanometry, acoustic rhinometry, peak nasal
      inspiratory flow, Odiosoft-Rhino, optical rhinometry, 24-h measurements,
      computational fluid dynamics, nasometry and the mirrow test were evaluated for
      important diagnostic criteria, which are the precision of the equipment including
      calibration and the software applied; validity with sensitivity, specificity,
      positive and negative predictive values, reliability with intra-individual and
      inter-individual reproducibility and responsiveness in clinical studies. For
      rhinomanometry, the logarithmic effective resistance was set as the parameter of
      high diagnostic relevance. In acoustic rhinometry, the area of interest for the
      minimal cross-sectional area will need further standardization. Peak nasal
      inspiratory flow is a reproducible and fast test, which showed a high range of
      mean values in different studies. The state of the art with computational fluid
      dynamics for the simulation of the airway still depends on high performance
      computing hardware and will, after standardization of the software and both the
      software and hardware for imaging protocols, certainly deliver a better
      understanding of the nasal airway flux.

PMID- 29353290
TI  - Postmodernity, addictive societies, cannabis and suicidal behaviour: Towards a
      brave new world?
AB  - Editorial of vol. 30-1.

PMID- 29353291
TI  - Editorial. Impact of the Binge Drinking (BD) in Adolescence. Are we doing it
      right? Editorial. Impacto del consumo episodico excesivo de alcohol en la
      adolescencia. ?Lo estamos haciendo bien?
AB  - Nowadays, one of the most prevalent patterns of alcohol consumption is called
      binge drinking (BD). In 2015, the European School Survey Project on Alcohol and
      Drugs (ESPAD) Group estimated that about 35% of adolescents of 15-16 years old
      have had at least one BD occasion in the past 30 days while at national level,
      the series of surveys on the use of drugs in adolescents of secondary education
      (ESTUDES, 2014-2015) determined that 32.2% of adolescents stated having performed
      BD in the last month. The aim of this editorial was to update the context of
      adolescence drinking and analysing the impact of BD by ages, including health and
      social costs derived. Once the magnitude of the problem was set, some research
      and action lines have been established in order to guide future work for the
      prevention of alcohol misuse and for establishing future preventive policies on
      alcohol. Finally, the need for evaluating these interventions from the efficiency
      point of view was discussed and assessed.

PMID- 29353292
TI  - Harm reduction program use, psychopathology and medical severity in patients with
      methadone maintenance treatment.
AB  - Methadone maintenance programs (MMP) for opioid dependence treatment have been
      widely used due to their effective therapeutic outcomes. Harm reduction programs
      (HRP) are complementary programs for severe patients with high risk behaviors and
      when abstinence is not possible. This study aims to compare patients in MMP that
      use HRP (MMP-HRP) and patients in MMP who do not use HRP (MMP-NO HRP). The sample
      was composed of 143 patients (MMP-HRP = 42 vs. MMP-NO HRP = 101). An additional
      subanalysis was performed with patients under 45 years of age (n = 116; MMP-HRP =
      38 vs. MMP-NO HRP = 78). All patients were assessed with an ad hoc socio
      demographic questionnaire, EuropASI, SCID-I, and SCID-II. Results show that MMP
      HRP patients were younger with more frequent use of intravenous drugs and with a
      high prevalence of Cluster B personality disorders. MMP-NO HRP patients had lower
      methadone doses compared to MMP-HRP patients and preferred to use drugs by smoked
      route more frequently. In the subanalysis of patients under 45, MMP-HRP patients
      were younger, had a higher prevalence of liver diseases, more intravenous drug
      use, greater severity on the drug use scale, less social and family support in
      the suescales of EUROP-ASI than compared to patients under 45 years in the group
      MMP-NO HRP. In conclusion, MMP-HRP patients are younger compared to MMP-NO HRP
      patients, they also receive higher doses of methadone and had more intravenous
      use. The above findings imply that the early onset of high risk drug use and long
      term exposure to heroin have more severe outcomes such as higher comorbidities
      (e.g. infectious diseases, medical and psychiatric disorders), and consequently,
      these patients are a more vulnerable group with a worse prognosis.

PMID- 29353293
TI  - Alcohol, tobacco and cannabis consumption in adolescents from a multicultural
      population (Burela, Lugo).
AB  - Social inequalities have been associated with morbidity and mortality. Gender,
      ethnic group and inequalities were studied in an adolescent population to analyze
      alcohol, tobacco and cannabis consumption. We carried out a cross-sectional study
      of pupils from high schools in Burela (northern Spain) (n=238). We used the
      "Factors de Risc en Estudiants de Secundaria" questionnaire designed by Agencia
      de Salut Publica de Barcelona. Independent variables: nationality and weekly
      pocket money. Dependent variables: expectations and consumption of alcohol,
      tobacco and marihuana. Logistic regression was used. Participation in the study
      reached 91%. The proportion of pupils that have tried alcohol on occasion
      increases with age (27.3%, 47.7%, 75.9%), as with tobacco (1.8%, 7.6%, 17.0%),
      and cannabis (0%, 3.1%, 7.0%). Higher levels of spending money constitute a risk
      factor for tasting alcohol (OR=3.01), for high-risk consumption (OR=3.35), for
      getting drunk (OR=6.45) and for trying marijuana (OR=15.30). Sex and nationality
      were not shown to be associated with the use of any of these three drugs. The
      results of our study show that consumption of alcohol, tobacco and cannabis
      increases with age and with increased spending money. The data do not support the
      argument that foreign pupils are a risk group for alcohol consumption, so they
      should not be stigmatized.

PMID- 29353294
TI  - Development and validation of the alcohol Expectancy Questionnaire Short Form (EQ
      SF).
AB  - Alcohol expectancies are proximal variables to alcohol use and misuse. In recent
      decades, different measures have been developed to assess this construct. One of
      the most frequently used and recommended instruments is the Expectancy
      Questionnaire (EQ; Leigh y Stacy, 1993). Our aim is to develop a short version of
      the EQ (EQ-SF) for suitable use in time-limited administrations. Two samples,
      adolescents (N = 514, 57.20% females) and adults (N = 548, 61.50% females),
      completed the EQ together with alcohol-use measures. Different item selection
      strategies were applied to select the 24 items. The EQ-SF structure was explored
      using confirmatory factor analysis, and measurement invariance was tested running
      a multi-group analysis comparing groups by sex and age. Reliability was tested
      using Cronbach's alpha and omega coefficients. Concurrent validity was
      investigated with regression analyses. The EQ-SF showed acceptable between-groups
      measurement invariance. Alphas and omegas ranged from .77 to .93. Positive
      expectancies predicted both alcohol use and alcohol-related problems. Negative
      expectancies predicted alcohol-related problems. Sex and age moderated these
      associations. Males with high positive alcohol expectancies showed higher alcohol
      consumption than females, while adults with high negative alcohol expectancies
      showed greater alcohol-related problems than adolescents. Different evidence on
      the validity and reliability of the EQ-SF suggest that it is a suitable
      instrument to assess alcohol expectancies in the Spanish population.

PMID- 29353295
TI  - Spanish version validation of the Marihuana Motives Measure in a drug-consuming
      adolescent sample.
AB  - INTRODUCTION: Cannabis is the illicit drug mostly widely consumed by adolescents
      in Spain. The understanding of consumption motives is an important factor for
      intervention. In Spain, there are no available instruments for their evaluation,
      hence, the goal of this paper is to study the psychometric properties of the
      Marihuana Motives Measure (MMM) in a sample of adolescent consumers. MATERIAL AND
      METHOD: Firstly, translation and back-translation was performed. A total of 228
      adolescent consumers of cannabis were evaluated. Factorial analysis was
      conducted, and the reliability of the total scores and of each scale of the
      questionnaire was studied through Cronbach's alpha. Test-retest reliability was
      analyzed through interclass correlations. Validity evidence of the MMM was
      examined through correlations between current cannabis use, subjective
      consumption effects measured with the Addiction Research Center Inventory (ARCI),
      and personality measured with the Millon Adolescent Clinical Inventory (MACI).
      RESULTS: High reliability was observed in total score of the MMM (Cronbach alpha
      = .86), and high and moderate reliability for each of the five factors obtained
      in the factorial analysis of the MMM, Social = .82, Enhancement = .72, Coping =
      .83, Expansion = .74, and Conformity = .64. Significant correlations were also
      observed between cannabis consumption motives and subjective effects, and between
      consumption motives and personality. CONCLUSION: The Spanish version of the MMM
      shows a similar factorial structure as the one obtained by the original author,
      and its measures are reliable and valid for the study of cannabis consumption
      motives in adolescent consumer population.

PMID- 29353296
TI  - The urban environment of alcohol: a study on the availability, promotion and
      visibility of its use in the neighborhoods of Barcelona.
AB  - INTRODUCTION: This paper describes the presence of alcohol in the public space,
      assessing establishments that offer it, its advertising, and signs of
      consumption, as factors that may influence its consumption. METHOD: Descriptive
      observational study based on cluster sampling with two-step selection. Results
      are described, and the spatial association between variables is assessed.
      RESULTS: In the 20 census tracts studied, 306 premises were identified that
      offered alcoholic beverages: 204 were on-premises and 102 were off-premises,
      mainly supermarkets and food retail stores. Their spatial distribution was
      uneven, concentrated in two central districts. We identified 72 publicity items,
      mostly sponsorship of musical events. There were many promotional items linked to
      on- premises, especially in their terraces. Five people were detected promoting
      consumption or selling alcohol in the Old Town. In each time slot, between 39 and
      51 signs of consumption on the public space were observed (mostly abandoned beer
      cans), more frequent at night and in the Old Town. There is an association
      between the presence of establishments that offer alcohol and advertising. There
      is no relationship between these variables and signs of consumption in the public
      space; these are concentrated in the Old Town, which has greater presence of
      tourism. CONCLUSIONS: The urban environment is characterized by elements that
      stimulate alcohol use and its distribution is uneven, with a strong influence of
      tourism-related activities. Further regulation of alcohol promotion, availability
      and consumption in the public space may change its social image and decrease its
      use.

PMID- 29353297
TI  - Individual and contextual factors related to binge drinking among adolescents in
      Spain: a multilevel approach.
AB  - The aim of this study was to estimate the prevalence of binge drinking by regions
      in Spain and assess the effect of individual and contextual factors related to
      this drinking pattern in adolescents. A cross-sectional study was performed with
      data from the 2014 Spanish School Survey on Drug Use (ESTUDES) in students aged
      14-18 years (N = 34,259). The outcome was binge drinking in adolescents during
      the last 30 days. Individual independent variables were socioeconomic variables
      and variables related to access to alcohol and its availability. Contextual
      variables consisted of adult alcohol consumption, public policies on alcohol, and
      socioeconomic factors. Multilevel Poisson regression models with robust variance
      were estimated, obtaining prevalence ratios (PR) and their 95% confidence
      intervals.  The results showed that the prevalence of youth binge drinking by
      region of residence was similar for both sexes (r = 0.72). At the individual
      level, binge drinking was mainly associated with the perception of easy access to
      alcohol (PR: 1.38; 95% CI: 1.23-1.55), consumption in open areas [(PR: 3.82; 95%
      CI: 3.44-4.24) < once a month and (PR: 6.57; 95% CI: 5.85-7.37) >= once a month],
      at least one parent allowing alcohol consumption (PR: 1.42; 95% CI: 1.37-1.47),
      and receiving >30 euros weekly (PR :1.51; 95% CI: 1.37-1.67). Contextual
      variables were not associated with youth binge drinking when individual variables
      were considered. In conclusion, youth binge drinking was associated with
      individual variables related to high alcohol accessibility and availability,
      regardless of contextual variables. These variables explained the variability in
      binge drinking among Spanish regions.

PMID- 29353298
TI  - Development and Validation of the Marijuana Motives Measure Short Form.
AB  - Marijuana motives are a proximal variable to marijuana use. This research aimed
      to adapt and validate the short form of the Marijuana Motives Measure (MMM;
      Simons, Correia, Carey, y Borsari, 1998), the MMM SF, in Spanish.  The sample
      comprised 232 participants (mean age = 25.11 (7.58), 50.43% males) who had tried
      marijuana at least once in their lifetime. Item and Rasch analyses were performed
      to choose the final pool of 15 items. Confirmatory Factor Analysis (CFA) showed
      an adequate 5-factor structure (S-BX2(80) = 121.30, p = .002; NNFI = .944; CFI =
      .958; IFI = .959; MFI = .915; RMSEA = .047(0.029, 0.063); AIC = -38.70), and the
      multi-group CFA between males and females showed acceptable fit indices (S
      BX2(160) = 230.01, p = .000; NNFI = .900; CFI = .924; IFI = .927; MFI = .860;
      RMSEA = .062(.043, .078); AIC = -89.99). The questionnaire indicated metric (S
      BX2diff (15) = 13.61, p = .556)), scalar (S-BX2diff (15) = 23.15, p = .081)) and
      error measurement invariance (S-BX2diff (15) = 8.65, p = .895)) between gender
      groups. The internal consistencies and ordinal omega of the scales were between
      .79 and .90. In the regression analysis, enhancement, coping and low conformity
      motives predicted frequency and quantity of marijuana smoked. The best predictor
      of frequency and quantity consumed during the heaviest smoking period was
      enhancement, while coping and, to a lesser extent, low conformity, were the only
      predictors of cannabis-related problems when marijuana frequency and quantity
      were controlled for.  The MMM SF shows adequate psychometric properties and is a
      suitable instrument to assess marijuana motives, especially during time-limited
      sessions.

PMID- 29353299
TI  - Creation of the TXP parenting questionnaire and study of its psychometric
      properties.
AB  - Parenting is linked to conduct disorders (CD) and substance related disorders
      (SRD) in adolescents, but with differences according to cultural context. A
      questionnaire with two versions (parenting questionnaire TXP-A for adolescents
      and TXP-C  for primary caregivers) was designed using the Delphi method to
      evaluate parenting practices related to CD and SRD in a Spanish population. It
      was validated in a community sample of 631 adolescents aged between 14 and 16 and
      their caregivers. Results suggest a 29-item TXP-A questionnaire with bifactorial
      structure: affection-communication and control-structure, with high internal
      (Cronbach&rsquo;s alpha=0.89) and test-retest (intraclass correlation
      coefficient=0.94) reliabilities. Both factors are related to SRD (r=0.273,
      p<0.001) and with most of the psychopathological dimensions studied. The total
      score and affection-communication are related to dissocial disorder (t=3.259,
      p=0.001) and its severity (r=-0,119; p=0.003). Inter-observer reliability between
      adolescents and caregivers is low, in part because the 16-item TXP-C has a
      different bifactorial structure: affection-communication and prosocial values.
      TXP-C&rsquo;s internal (Cronbach&rsquo;s alpha=0.87) and test-retest (intraclass
      correlation coefficient=0.94) reliabilities are high. The total score and
      affection-communication were related to dissocial disorder (t=2.586; p=0.010) but
      TXP-C did not discriminate according to SRD. In conclusion, the TXP-A
      questionnaire for adolescents seems to be a reliable, valid and unbiased
      instrument that evaluates the perception of parenting practices, relating higher
      affection-communication and control-structure to less psychopathology and alcohol
      and drug use. TXP-C also seems to be reliable and unbiased, but shows less
      evidence of validity regarding substance use and psychopathology.&nbsp.

PMID- 29353300
TI  - Empirical validation of the CRAFFT Abuse Screening Test in a Spanish sample.
AB  - The CRAFFT Substance Abuse Screening Instrument, developed by the Center for
      Adolescents Substance Abuse Research (CeASAR) (Knight et al., 1999), is a
      screening tool for high-risk alcohol and drug risk consumption designed for use
      with adolescents. Since its publication it has been the subject of translations
      and validations in different countries, populations and contexts that have
      demonstrated its enormous potential. However, there is still no empirical
      validation study that would ensure its good psychometric performance in Spain.
      The aim of this paper is to develop an adapted version of the CRAFFT in Spanish
      and to analyze its psychometric properties in a sample of Spanish adolescents.
      For this purpose an individual interview was conducted on 312 adolescents aged
      between 12 and 18 years of age (M = 15.01; SD = 1.83) from the Galician
      community. The interview included a part of the Adolescent Diagnostic Interview
      (ADI) and the Problem Oriented Screening Instrument for Teenagers (POSIT). The
      results obtained, similar to those found in other countries, allow us to report
      that the Spanish version of the CRAFFT has a good psychometric
      behaviorproperties. It was found to have a satisfactory internal consistency with
      a Cronbach&rsquo;s alpha value of .74. In terms of sensitivity and specificity,
      values of 74.4% and 96.4% respectively, were obtained and the area under the ROC
      curve was .946. The Spanish version of the CRAFFT is made available to
      researchers and professionals in the field of addictive behaviors, so that it can
      be used with the necessary psychometric guarantees.

PMID- 29353301
TI  - The efficacy of Motivational Intervention and Cognitive-Behavioral Therapy for
      Pathological Gambling.
AB  - The aim of the current study is to determine the effectiveness of an individual
      psychological intervention based on the motivational interview and cognitive
      behavioral therapy for the treatment of pathological gambling. A sample of 18
      participants, diagnosed of pathological gambling and without any other associated
      comorbidity, were assessed, attended at the publicly-funded Gambling and
      Behavioral Addictions Unit (Consorci Sanitari de Terrassa). Median age was 46
      years (SD = 12). All the patients achieved abstinence and completed follow-up.
      The Screen for Gambling Problems (NODS), Quality of Life Enjoyment and
      Satisfaction (Q-LES-Q), Impulsive Behavior Scale (UPPS-P), Sheehan Disability
      Inventory (SDI), Beck Depression Inventory (BDI) and State-Trait Anxiety
      Inventory (STAI) were administered pre- and posttreatment. Results showed that
      patients significantly reduced the problems related to gambling behavior
      according to the NODS score (p < .000). Regarding impulsive behavior (UPPS-P), we
      found significant differences in negative urgency (p < .001), positive urgency (p
      < .001), (lack of) premeditation (p < .029) and (lack of) perseverance (p <
      .048). Some relevant aspects of quality of life as assessed by the Q-LES-Q had
      improved. In conclusion, the study shows that psychological intervention based on
      the motivational interview and cognitive-behavioral therapy not only
      significantly reduces gambling-related behavior problems but also leads to
      improvements in impulsivity and quality of life.&nbsp.

PMID- 29353302
TI  - "Diazepam loading": ?Can a strategy for preventing alcohol withdrawal be used to
      treat benzodiazepine use disorder?
AB  - Benzodiazepines (BZDs) are central nervous system (CNS) depressants which are
      widely used to treat insomnia and anxiety, despite having long-term adverse side
      effects. (Fortea Gonzalez, Oriolo, Balcells Olivero, Sanchez Del Valle &
      Castellvi, 2017). As with alcohol, continued use can lead to tolerance and
      dependence phenomena. Discontinuation in such cases can produce abstinence
      symptoms such as tremors, anxiety, seizures and, occasionally, death (Brett y
      Murnion, 2015).

PMID- 29353303
TI  - Chemsex: are we prepared?
AB  - It was with great interest that we read the article published by Dolengevich
      Segal (Dolengevich-Segal et al., 2017), which provides an interesting review of
      the emerging phenomenon known as chemsex and the different drugs used in this
      type of practice.We would like to highlight the importance and usefulness of this
      paper, given the progressive increase in the prevalence of drug use in the
      context of sexual activity among men who have sex with men (MSM) in Western
      Europe (Fernandez-Davila et al,. 2016). This situation raises the need to launch
      epidemiological studies to assess the phenomenon - not only, however, from the
      point of view of mental health, but also from the field of infectious diseases
      and toxicology. We must not forget that this type of practice involves an
      increase in the risk of infection by sexually transmitted diseases and the
      problems that drug use can cause from the toxicological point of view. Both are
      causes of emergency room (ER) consultation, and more training in how to tackle
      the problems arising from chemsex should be provided.

PMID- 29353304
TI  - Unraveling the heterogeneity of IgM monoclonal gammopathies: a gene mutational
      and gene expression study.
AB  - Immunoglobulin M (IgM) monoclonal gammopathies show considerable variability,
      involving three different stages of presentation: IgM monoclonal gammopathy of
      undetermined significance (IgM-MGUS), asymptomatic Waldenstrom's
      macroglobulinemia (AWM), and symptomatic WM (SWM). Despite recent findings about
      the genomic and transcriptomic characteristics of such disorders, we know little
      about the causes of this clinical heterogeneity or the mechanisms involved in the
      progression from indolent to symptomatic forms. To clarify these matters, we have
      performed a gene expression and mutational study in a well-characterized cohort
      of 69 patients, distinguishing between the three disease presentations in an
      attempt to establish the relationship with the clinical and biological features
      of the patients. Results showed that the frequency of genetic alterations
      progressively increased from IgM-MGUS to AWM and SWM. This means that, in
      contrast to MYD88 p.L265P and CXCR4 WHIM mutations, present from the beginning of
      the pathogenesis, most of them would be acquired during the course of the
      disease. Moreover, the expression study revealed a higher level of expression of
      genes belonging to the Toll-like receptor (TLR) signaling pathway in symptomatic
      versus indolent forms, which was also reflected in the disease presentation and
      prognosis. In conclusion, our findings showed that IgM monoclonal gammopathies
      present higher mutational burden as the disease progresses, in parallel to the
      upregulation of relevant pathogenic pathways. This study provides a translational
      view of the genomic basis of WM pathogenesis.

PMID- 29353305
TI  - An Investigation of the Critical Events and Influential Factors to the Evolution
      of the U.S. Man and the Biosphere Program.
AB  - The UNESCO Man and the Biosphere program has operated for 45 years as an
      international program that started in the 1970s to conserve biotic communities
      and provide areas for research, education, and training. The program later
      evolved in the 1990s to address social and environmental issues in a sustainable
      manner across a landscape. This program was one of the first efforts that
      recognized the importance of working beyond park and protected area boundaries
      and the need to sustain livelihoods as much as the resources. In the MAB
      program's infancy, the United States (U.S.) was a major advocate and leader with
      more than 45 biosphere reserves, most of them established in or around 1976. Yet,
      many political, economic, and other external factors influenced the U.S. MAB
      involvement in subsequent years. Consequently, the U.S. has remained largely
      inactive in the international MAB network for the past fifteen years until a
      recent push to revive the program under the leadership of the State Department
      and the National Park Service. Through in-depth research on two longterm U.S.
      biosphere reserves, this paper provides a description of the key events impacting
      the U.S. MAB program over the past several decades and discusses the influential
      role of politics, a public image, and the perceptions of international
      designations. Through the lessons presented in this paper, recommendations are
      provided to support the revival of the MAB program in the U.S.

PMID- 29353306
TI  - Toxoplasma gondii antigen SAG2A differentially modulates IL-1beta expression in
      resistant and susceptible murine peritoneal cells.
AB  - The cell surface of Toxoplasma gondii is covered by antigens (SAGs) from the SRS
      family anchored by glycosylphosphatidylinositol (GPI) and includes antigens from
      the SAG2 family. Among these, the SAG2A surface antigen shows great potential in
      activating humoral responses and has been used in characterizing the acute phase
      of infection and in the serological diagnosis of toxoplasmosis. In this study, we
      aimed to evaluate rSAG2A-induced proteins in BALB/c and C57BL/c mice macrophages
      and to evaluate the phenotypic polarization induced in the process. We treated
      the peritoneal macrophages from mouse strains that were resistant or susceptible
      to T. gondii with rSAG2A to analyze their proteomic profile by mass spectrometry
      and systems biology. We also examined the gene expression of these cells by RT
      qPCR using the phenotypic markers of M1 and M2 macrophages. Differences were
      observed in the expression of proteins involved in the inflammatory process in
      both resistant and susceptible cells, and macrophages were preferentially induced
      to obtain a pro-inflammatory immune response (M1) via the overexpression of IL
      1beta in mice susceptible to this parasite. These data suggest that the SAG2A
      antigen induces phenotypic and classical activation of macrophages in both
      resistant and susceptible strains of mice during the acute phase of the disease.

PMID- 29353307
TI  - Characterization of an alpha-agarase from Thalassomonas sp. LD5 and its
      hydrolysate.
AB  - It has been a long time since the first alpha-agarase was discovered. However,
      only two alpha-agarases have been cloned and partially characterized so far and
      the study of alpha-agarases has lagged far behind that of beta-agarases. Here, we
      report an alpha-agarase, AgaD, cloned from marine bacterium Thalassomonas sp.
      LD5. Its cDNA consists of 4401 bp, encoding a protein of 1466 amino acids. Based
      on amino acid similarity, AgaD is classified into glycoside hydrolase (GH) family
      GH96. The recombinant enzyme gave a molecular weight of about 180 kDa on SDS-PAGE
      and 360 kDa on Native-PAGE indicating it acted as a dimer. However, the
      recombinant enzyme is labile and easy to be fractured into series of small active
      fragments, of which the smallest one is about 70 kDa, matching the size of
      catalytic module. The enzyme has maximal activity at 35  degrees C and pH 7.4,
      and shows a strong dependence on the presence of calcium ions. AgaD degrades
      agarose to yield agarotetraose as the predominate end product. However, the
      hydrolysates are rapidly degraded to odd-numbered oligosaccharides under strong
      alkaline condition. The spectra of ESI-MS and 1H-NMR proved that the main
      hydrolysate agarotetraose is degraded into neoagarotriose, bearing the sequence
      of G-A-G (G, D-galactose; A, 3,6-anhydro-alpha-L-galactose). Unlike the alkaline
      condition, the hydrolysates are further hydrolyzed into smaller degree
      polymerization (DP) of agaro-oligosaccharides (AOS) in dilute strong acid.
      Therefore, this study provides more insights into the properties for both the
      alpha-agarases and the AOS.

PMID- 29353308
TI  - Single-stage autotrophic nitrogen removal process at high loading rate: granular
      reactor performance, kinetics, and microbial characterization.
AB  - For the possible highest performance of single-stage combined partial
      nitritation/anammox (PNA) process, a continuous complete-mix granular reactor was
      operated at progressively higher nitrogen loading rate. The variations in
      bacterial community structure of granules were also characterized using high
      throughput pyrosequencing, to give a detail insight to the relationship between
      reactor performance and functional organism abundance within completely
      autotrophic nitrogen removal system. In 172 days of operation, a superior total
      nitrogen (TN) removal rate over 3.9 kg N/(m3/day) was stable implemented at a
      fixed dissolved oxygen concentration of 1.9 mg/L, corresponding to the maximum
      specific substrate utilization rate of 0.36/day for TN based on the related
      kinetics modeling. Pyrosequencing results revealed that the genus Nitrosomonas
      responsible for aerobic ammonium oxidation was dominated on the granule surface,
      which was essential to offer the required niche for the selective enrichment of
      anammox bacteria (genus Candidatus Kuenenia) in the inner layer. And the present
      of various heterotrophic organisms with general functions, known as fermentation
      and denitrification, could not be overlooked. In addition, it was believed that
      an adequate excess of ammonium in the bulk liquid played a key role in
      maintaining process stability, by suppressing the growth of nitrite-oxidizing
      bacteria through dual-substrate competitions.

PMID- 29353309
TI  - Methods for enhancing cyanobacterial stress tolerance to enable improved
      production of biofuels and industrially relevant chemicals.
AB  - Cyanobacteria are photosynthetic prokaryotes that can fix atmospheric CO2 and can
      be engineered to produce industrially important compounds such as alcohols, free
      fatty acids, alkanes used in next-generation biofuels, and commodity chemicals
      such as ethylene or farnesene. They can be easily genetically manipulated, have
      minimal nutrient requirements, and are quite tolerant to abiotic stress making
      them an appealing alternative to other biofuel-producing microbes which require
      additional carbon sources and plants which compete with food crops for arable
      land. Many of the compounds produced in cyanobacteria are toxic as titers
      increase which can slow growth, reduce production, and decrease overall biomass.
      Additionally, many factors associated with outdoor culturing of cyanobacteria
      such as UV exposure and fluctuations in temperature can also limit the production
      potential of cyanobacteria. For cyanobacteria to be utilized successfully as
      biofactories, tolerance to these stressors must be increased and ameliorating
      stress responses must be enhanced. Genetic manipulation, directed evolution, and
      supplementation of culture media with antioxidants are all viable strategies for
      designing more robust cyanobacterial strains that have the potential to meet
      industrial production goals.

PMID- 29353311
TI  - Effects of wrist tendon vibration and eye movements on manual aiming.
AB  - In the present study, we investigated whether visual information mediates a
      proprioceptive illusion effect induced by muscle tendon vibration in manual
      aiming. Visual information was gradually degraded from a situation in which the
      targets were present and participants (n = 20; 22.3 +/- 2.7 years) were permitted
      to make saccadic eye movements to designated target positions, to a condition in
      which the targets were not visible and participants were required to perform
      cyclical aiming while fixating a point between the two target positions. Local
      tendon vibration applied to the right wrist extensor muscles induced an illusory
      reduction of 15% in hand movement amplitude. This effect was greater in the
      fixation than in the saccade condition. Both anticipatory control and
      proprioceptive feedback are proposed to contribute to the observed effects. The
      primary saccade amplitude was also reduced by almost 4% when muscle tendon
      vibration was locally applied to the wrist. These results confirm a tight link
      between eye movements and manual perception and action. Moreover, the impact of
      the proprioceptive illusion on the ocular system indicates that the interaction
      between systems is bidirectional.

PMID- 29353310
TI  - NOD-like receptor(s) and host immune responses with Pseudomonas aeruginosa
      infection.
AB  - INTRODUCTION: Molecular mechanisms underlying the interactions between
      Pseudomonas aeruginosa, the common opportunistic pathogen in cystic fibrosis
      individuals, and host induce a number of marked inflammatory responses and
      associate with complex therapeutic problems due to bacterial resistance to
      antibiotics in chronic stage of infection. METHODS: Pseudomonas aeruginosa is
      recognized by number of pattern recognition receptors (PRRs); NOD-like receptors
      (NLRs) are a class of PRRs, which can recognize a variety of endogenous and
      exogenous ligands, thereby playing a critical role in innate immunity. RESULTS:
      NLR activation initiates forming of a multi-protein complex called inflammasome
      that induces activation of caspase-1 and resulted in cleavage of pro-inflammatory
      cytokines interleukin (IL)-1beta and IL-18. When the IL-1beta is secreted
      excessively, this causes tissue damage and extensive inflammatory responses that
      are potentially hazardous for the host. CONCLUSIONS: Recent evidence has laid out
      inflammasome-forming NLR far beyond inflammation. This review summarizes current
      knowledge regarding the various roles played by different NLRs and associated
      down-signals, either in recognition of P. aeruginosa or may be associated with
      such bacterial pathogen infection, which may relate to for the complexity of lung
      diseases caused by P. aeruginosa.

PMID- 29353313
TI  - General solution of the chemical master equation and modality of marginal
      distributions for hierarchic first-order reaction networks.
AB  - Multimodality is a phenomenon which complicates the analysis of statistical data
      based exclusively on mean and variance. Here, we present criteria for
      multimodality in hierarchic first-order reaction networks, consisting of
      catalytic and splitting reactions. Those networks are characterized by
      independent and dependent subnetworks. First, we prove the general solvability of
      the Chemical Master Equation (CME) for this type of reaction network and thereby
      extend the class of solvable CME's. Our general solution is analytical in the
      sense that it allows for a detailed analysis of its statistical properties. Given
      Poisson/deterministic initial conditions, we then prove the independent species
      to be Poisson/binomially distributed, while the dependent species exhibit
      generalized Poisson/Khatri Type B distributions. Generalized Poisson/Khatri Type
      B distributions are multimodal for an appropriate choice of parameters. We
      illustrate our criteria for multimodality by several basic models, as well as the
      well-known two-stage transcription-translation network and Bateman's model from
      nuclear physics. For both examples, multimodality was previously not reported.

PMID- 29353312
TI  - Child labour and health: a systematic review.
AB  - OBJECTIVES: This study aimed to synthesise the available knowledge, identify
      unexplored areas and discuss general limits of the published evidence. We focused
      on outcomes commonly hypothesised to be affected by child labour: nutritional
      status, harmful exposures and injuries. METHODS: Four electronic databases
      (EMBASE, MEDLINE, Scopus, ISI Web of Science) were searched in November 2017. All
      articles published since 1996, without restrictions on language, were considered
      for inclusion. RESULTS: Out of the 1090 abstracts initially identified by the
      search, 78 articles were selected for inclusion and reviewed. Most of the studies
      were conducted in Asia and South America, and only a third of them compared
      working children to a control group of non-working children. Child labour appears
      to be associated with poor nutritional status, diseases due to harmful exposures,
      and a higher prevalence of injuries. CONCLUSIONS: Despite evidence for a negative
      relation between child work and health, the cross-sectional design of most
      studies limits the causal interpretation of existing findings. More rigorous
      observational studies are needed to confirm and better quantify these
      associations.

PMID- 29353315
TI  - Whole grain intakes in Irish adults: findings from the National Adults Nutrition
      Survey (NANS).
AB  - PURPOSE: Observational studies link high whole grain intakes to reduced risk of
      many chronic diseases. This study quantified whole grain intakes in the Irish
      adult population and examined the major contributing sources. It also
      investigated potential dietary strategies to improve whole grain intakes.
      METHODS: Whole grain intakes were calculated in a nationally representative
      sample of 1500 Irish adults using data from the most recent national food survey,
      the National Adult Nutrition Survey (NANS). Food consumption was assessed, at
      brand level where possible, using a 4-day semi-weighed food diary with whole
      grain content estimated from labels on a dry matter basis. RESULTS: Mean daily
      whole grain intakes were 27.8 +/- 29.4 g/day, with only 19% of the population
      meeting the quantity-specific recommendation of 48 g per day. Wheat was the
      highest contributor to whole grain intake at 66%, followed by oats at 26%. High
      whole grain intakes were associated with higher dietary intakes of fibre,
      magnesium, potassium, phosphorus, and a higher alternative Mediterranean Diet
      Score. Whole grain foods were most frequently eaten at breakfast time. Regression
      analysis revealed that consumption of an additional 10 g of whole grain
      containing 'ready-to-eat breakfast cereals', 'rice or pastas', or 'breads' each
      day would increase intake of whole grains by an extra 5, 3.5, and 2.7 g,
      respectively. CONCLUSIONS: This study reveals low intakes of whole grains in
      Irish adults. Recommending cereals, breads, and grains with higher whole grain
      content as part of public health campaigns could improve whole grain intakes.

PMID- 29353314
TI  - Robot-assisted post-chemotherapy retroperitoneal lymph node dissection in germ
      cell tumor: is the single-docking with lateral approach relevant?
AB  - INTRODUCTION: Surgical treatment of post-chemotherapy residual mass of germ cell
      tumor (GCT) may be performed in various techniques. We assess the feasibility,
      safety, and efficacy of single-docking with lateral approach robot-assisted
      retroperitoneal lymph node dissection (R-RPLND) in residual mass of GCT in our
      center. MATERIALS AND METHODS: A retrospective review of patients undergoing R
      RPLND for residual mass of CGT was performed between January 2014 and April 2017.
      Patients with residual mass < 3 cm for seminoma or < 1 cm for non-seminoma were
      eligible. All surgeries were performed with single-docking RPNLD technique in
      lateral decubitus. We assessed preoperative characteristics (age, testicular
      pathology, template, chemotherapy regimen, lesion size, and clinical stage),
      peroperative (operative time, estimated blood loss, intraoperative complication,
      node count, pathology, and number of positive node), and postoperative outcomes
      (postoperative complications, hospital length of stay, recurrence-free survival
      at 2 year, and ejaculation dysfunction). RESULTS: Eleven patients underwent R
      RPLND with a median size of the residual mass of 20 mm. Median operative time was
      153 min with 120 ml of estimated blood loss, without intraoperative complication.
      Median nodes count was 7 [1; 24]. Two patients had post-chemotherapy necrotic
      nodes and one no tumorous node. One patient had postoperative Clavien I
      complication (chyloperitoneum). We report 72.7% of antegrade ejaculation at 1
      month from the surgery. Median clinical recurrence-free survival was 100% after 2
      years from the surgery (n = 6). CONCLUSION: Lateral approach with single-docking
      R-RPLND for residual mass of GCT is feasible and safe, with satisfying functional
      and oncologic outcomes.

PMID- 29353316
TI  - Validation of a new classification for periprosthetic shoulder fractures.
AB  - INTRODUCTION: Successful treatment of periprosthetic shoulder fractures depends
      on the right strategy, starting with a well-structured classification of the
      fracture. Unfortunately, clinically relevant factors for treatment planning are
      missing in the pre-existing classifications. Therefore, the aim of the present
      study was to describe a new specific classification system for periprosthetic
      shoulder fractures including a structured treatment algorithm for this important
      fragility fracture issue. METHODS: The classification was established, focussing
      on five relevant items, naming the prosthesis type, the fracture localisation,
      the rotator cuff status, the anatomical fracture region and the stability of the
      implant. After considering each single item, the individual treatment concept can
      be assessed in one last step. To evaluate the introduced classification, a
      retrospective analysis of pre- and post-operative data of patients, treated with
      periprosthetic shoulder fractures, was conducted by two board certified trauma
      surgery consultants. RESULTS: The data of 19 patients (8 male, 11 female) with a
      mean age of 74 +/- five years have been analysed in our study. The suggested
      treatment algorithm was proven to be reliable, detected by good clinical outcome
      in 15 of 16 (94%) cases, where the suggested treatment was maintained. Only one
      case resulted in poor outcome due to post-operative wound infection and had to be
      revised. CONCLUSIONS: The newly developed six-step classification is easy to
      utilise and extends the pre-existing classification systems in terms of
      clinically-relevant information. This classification should serve as a simple
      tool for the surgeon to consider the optimal treatment for his patients.

PMID- 29353318
TI  - Diagnostic Value of Vascular Endothelial Growth Factor, Transforming Growth
      Factor-beta, Interleukin-8, and the Ratio of Lactate Dehydrogenase to Adenosine
      Deaminase in Pleural Effusion.
AB  - PURPOSE: We studied the diagnostic value of cytokines, including vascular
      endothelial growth factor (VEGF), transforming growth factor-beta (TGF-beta), and
      interleukin-8 (IL-8), and the ratio of lactate dehydrogenase (LDH) to adenosine
      deaminase (ADA) in pleural fluid. METHODS: Prospective analysis of 44 inpatients
      or outpatients with pleural fluid, from December 2016 to March 2017 was
      conducted. RESULTS: We enrolled patients with malignant pleural effusion (MPE, N
      = 15), empyema (N = 11), parapneumonic effusion (PPE, N = 7), chronic renal
      failure (CRF)/chronic heart failure (CHF) (N = 7), and tuberculous pleural
      effusion (TBPE, N = 4). The pleural fluid values of IL-8 and VEGF were
      significantly higher in empyema patients than in CRF/CHF or PPE patients. In all
      patients, the pleural fluid VEGF and IL-8 values were significantly positively
      correlated (r = 0.405, p = 0.006; r = 0.474, p = 0.047, respectively). TGF-beta
      was elevated in patients with empyema, PPE, TBPE, and MPE. The pleural LDH-to-ADA
      ratio in patients with MPE or empyema/PPE was significantly higher than in
      patients with CRF/CHF or TBPE. LDH and ADA levels correlated significantly only
      in patients with MPE (r = 0.648, p = 0.009) and empyema/PPE (r = 0.978, p <
      0.001). CONCLUSIONS: VEGF and IL-8 production in the pleural cavity appear to
      accelerate the progression of PPE to empyema, by enhancing vascular permeability
      associated with inflammation. Sequential sampling would be needed to confirm
      this. The pleural LDH/ADA ratio may be a useful diagnostic tool for
      discriminating between various pleural effusion etiologies.

PMID- 29353317
TI  - Tumor suppressor C-RASSF proteins.
AB  - Human genome has ten genes that are collectedly called Ras association domain
      family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N
      RASSF and C-RASSF encode Ras association domain-containing proteins and are
      frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF
      and N-RASSF are quite different. Six C-RASSF proteins (RASSF1-6) are
      characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo
      domain, while four N-RASSF proteins (RASSF7-10) lack it. C-RASSF proteins
      interact with mammalian Ste20-like kinases-the core kinases of the tumor
      suppressor Hippo pathway-and cross-talk with this pathway. Some of them share the
      same interacting molecules such as MDM2 and exert the tumor suppressor role in
      similar manners. Nevertheless, each C-RASSF protein has distinct characters. In
      this review, we summarize our current knowledge of how C-RASSF proteins play
      tumor suppressor roles and discuss the similarities and differences among C-RASSF
      proteins.

PMID- 29353319
TI  - Management Strategies for Noncardiac Surgery Following a Coronary Artery Event.
AB  - PURPOSE OF REVIEW: Coronary artery event includes acute coronary syndrome (ACS),
      percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG)
      surgery. Following such an event, risk of noncardiac surgery is increased. Of
      major concern is what can make this surgery safer? RECENT FINDINGS: High
      functional capacity improves cardiovascular (CV) risk; at least 4.0 metabolic
      equivalents (METs) on stress test are favorable. Risk scores can suggest need for
      further evaluation. Coronary angiography prior to surgery usually is not
      indicated since revascularization shows disappointing CV risk reduction results.
      Due to high association of peripheral arterial disease (PAD) with coronary artery
      disease (CAD), low ankle-brachial index (ABI) indicates increased CV risk. New
      perioperative beta blockade has shown disappointing benefit, but if ongoing
      should be continued. De novo perioperative beta blockade is for the highest CV
      risk patient undergoing noncardiac vascular surgery. Good evidence supports CV
      risk reduction from new or existing statin in the perioperative period,
      especially for the diabetic. Diabetics should also be on an angiotensin
      converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)
      secondarily, during the perioperative period to decrease 30-day perioperative
      mortality. Optimal timing of elective noncardiac surgery following a coronary
      artery event appears to be 180 days with CV risk decreased by a statin and an
      ACEI or an ARB.

PMID- 29353320
TI  - Monitoring and measurement of microalgae using the first derivative of absorbance
      and comparison with chlorophyll extraction method.
AB  - Monitoring of microalgae in water supplies and industrial applications are
      becoming increasingly important, yet there are few options available that are
      simple and accurate, and can provide real-time information. The present work
      illustrates a new method to determine the concentration of microalgae in water
      and wastewater using spectrophotometry and the first derivative of absorbance.
      Chlorella vulgaris was used as an indicator microalga, spiked in water samples
      representing a range of water qualities (distilled water, surface water, and
      wastewater), and correlations among C. vulgaris concentrations, absorbance, and
      the first derivative of absorbance measurements were investigated. In addition,
      detection limits were established and sensitivity analyses were carried out to
      determine the lowest C. vulgaris concentrations that can be confidently measured
      in different water matrices. Finally, the study compared the performance and
      detection limits of the spectrophotometry-based methods with the well-accepted
      chlorophyll extraction method. A strong linear relationship (R2 > 0.97) was found
      between C. vulgaris concentration and absorbance at 695 nm. Using the first
      derivative of absorbance improved C. vulgaris detection limits by reducing the
      effects of the background noise and interferences from other substances. The
      detection limits established using the first derivative method were 0.47, 0.56,
      and 1.96 mg TVS/L in distilled water, surface water, and wastewater,
      respectively. In comparison, the detection limits of the chlorophyll extraction
      method were found to be 19.6, 38.6, and 48.3 mg TVS/L in the same water matrices.
      These results indicate that first derivative of absorbance can be successfully
      used for monitoring of microalgae in surface waters and environmental samples as
      well as in bioreactors used for microalgae cultivation in industrial
      applications.

PMID- 29353323
TI  - Does methylphenidate improve academic performance? A systematic review and meta
      analysis.
AB  - Academic improvement is amongst the most common treatment targets when
      prescribing stimulants to children with ADHD. Previous reviews on stimulant
      related academic improvements are inconclusive and focus on task engagement.
      Recent literature suggests outcome-domain-specific medication effects that are
      larger for productivity than for accuracy. The aims of this study are quantifying
      methylphenidate effects on academic productivity and accuracy for math, reading,
      spelling; exploring the mediating or moderating effects of symptom improvements,
      demographic-, design- and disorder-related variables. PubMed, EMBASE, ERIC and
      PsycINFO were searched for articles reporting methylphenidate effects on academic
      productivity and accuracy. Thirty-four studies met entry criteria.
      Methylphenidate improved math productivity (7.8% increase, p < .001); math
      accuracy (3.0% increase, p = .001); increased reading speed (SMD .47, p < .001)
      but not reading accuracy. None of the mediators or moderators tested affected
      methylphenidate efficacy. Academic improvements were small compared to symptom
      improvements; qualitative changes limited to math. Clinicians should take this
      discrepancy into account when prescribing medication for ADHD.

PMID- 29353322
TI  - Statistical analysis of phase formation in 2D colloidal systems.
AB  - Colloidal systems offer unique opportunities for the study of phase formation and
      structure since their characteristic length scales are accessible to visible
      light. As a model system the two-dimensional assembly of colloidal magnetic and
      non-magnetic particles dispersed in a ferrofluid (FF) matrix is studied by
      transmission optical microscopy. We present a method to statistically evaluate
      images with thousands of particles and map phases by extraction of local
      variables. Different lattice structures and long-range connected branching chains
      are observed, when tuning the effective magnetic interaction and varying particle
      ratios.

PMID- 29353321
TI  - Energy expenditure of rugby players during a 14-day in-season period, measured
      using doubly labelled water.
AB  - Criterion data for total energy expenditure (TEE) in elite rugby are lacking,
      which prediction equations may not reflect accurately. This study quantified TEE
      of 27 elite male rugby league (RL) and rugby union (RU) players (U16, U20, U24
      age groups) during a 14-day in-season period using doubly labelled water (DLW).
      Measured TEE was also compared to estimated, using prediction equations. Resting
      metabolic rate (RMR) was measured using indirect calorimetry, and physical
      activity level (PAL) estimated (TEE:RMR). Differences in measured TEE were
      unclear by code and age (RL 4369 +/- 979; RU 4365 +/- 1122; U16, 4010 +/- 744;
      U20, 4414 +/- 688; U24, 4761 +/- 1523 Kcal day- 1). Differences in PAL (overall
      mean 2.0 +/- 0.4) were unclear. Very likely differences were observed in RMR by
      code (RL 2366 +/- 296; RU 2123 +/- 269 Kcal day- 1). Differences in relative RMR
      between U20 and U24 were very likely (U16, 27 +/- 4; U20, 23 +/- 3; U24, 26 +/- 5
      Kcal kg- 1 day- 1). Differences were observed between measured and estimated TEE,
      using Schofield, Cunningham and Harris-Benedict equations for U16 (187 +/- 614,
      unclear; - 489 +/- 564, likely and - 90 +/- 579, unclear Kcal day- 1), U20 (- 449
      +/- 698, likely; - 785 +/- 650, very likely and - 452 +/- 684, likely Kcal day-
      1) and U24 players (- 428 +/- 1292; - 605 +/- 1493 and - 461 +/- 1314 Kcal day-
      1, all unclear). Rugby players have high TEE, which should be acknowledged. Large
      inter-player variability in TEE was observed demonstrating heterogeneity within
      groups, thus published equations may not appropriately estimate TEE.

PMID- 29353324
TI  - Stromalized microreactor supports murine hematopoietic progenitor enrichment.
AB  - There is an emerging need to process, expand, and even genetically engineer
      hematopoietic stem and progenitor cells (HSPCs) prior to administration for blood
      reconstitution therapy. A closed-system and automated solution for ex vivo HSC
      processing can improve adoption and standardize processing techniques. Here, we
      report a recirculating flow bioreactor where HSCs are stabilized and enriched for
      short-term processing by indirect fibroblast feeder coculture. Mouse 3 T3
      fibroblasts were seeded on the extraluminal membrane surface of a hollow fiber
      micro-bioreactor and were found to support HSPC cell number compared to
      unsupported BMCs. CFSE analysis indicates that 3 T3-support was essential for the
      enhanced intrinsic cell cycling of HSPCs. This enhanced support was specific to
      the HSPC population with little to no effect seen with the Lineagepositive and
      Lineagenegative cells. Together, these data suggest that stromal-seeded hollow
      fiber micro-reactors represent a platform to screening various conditions that
      support the expansion and bioprocessing of HSPCs ex vivo.

PMID- 29353326
TI  - Radiological and functional outcomes of high-grade spondylolisthesis treated by
      intrasacral fixation, dome resection and circumferential fusion: a retrospective
      series of 20 consecutive cases with a minimum of 2 years follow-up.
AB  - PURPOSE: Major concern during surgery for high-grade spondylolisthesis (HGS) is
      to reduce lumbosacral kyphosis and restore sagittal alignment. Despite the
      numerous methods described, lumbosacral fixation in HGS is a challenging
      technique associated with high complication rate. Few series have described
      outcomes and most of the results are limited to lumbosacral correction without
      global sagittal alignment analysis. This study aims at analyzing clinical and
      radiological outcomes of HGS patients treated with intrasacral rods on full spine
      radiographs. METHODS: HGS patients (Meyerding III or higher) operated between
      2004 and 2014 were reviewed. All patients underwent full spine stereoradiographic
      images. After L5 and S1 decompression, reduction and circumferential fusion with
      intrasacral rod fixation and fusion up to L4 were performed under fluoroscopy.
      The entry points for S1 screws were located 3-5 mm above and 5 mm lateral to the
      first sacral hole, toward the promontory. The two short distal fusion rods were
      then positioned into the sacrum guided by anteroposterior fluoroscopy using
      Jackson's technique. Then, sacral dome resection was performed and a PEEK cage
      was impacted in L5S1 after reduction. Postoperatively, the hip and knee were kept
      flexed at 45 degrees  for 1 week and extended progressively. Preoperative, 3
      months postoperative and last follow-up (> 2 years minimum) clinical and
      radiographic data were collected. Sagittal parameters included lumbosacral angle
      (LSA), olisthesis, T1 spinopelvic inclination (T1SPi) and spinopelvic parameters.
      RESULTS: 20 HGS patients were included (8 ptosis, 5 Meyerding IV). The mean age
      was 14 years. At final FU (7.2 years +/- 3), LSA kyphosis and olisthesis were
      reduced (65 degrees  +/- 14 vs 99 degrees  +/- 11, p < 0.001 and 81% +/- 19 vs
      45% +/- 18, p < 0.001, respectively). While L1L5 lordosis decreased, T1T12
      kyphosis increased. At FU, global alignment with T1SPi was - 6 degrees  +/- 3. No
      significant loss of correction was observed. Regarding complications, ten
      patients presented transient L5 motor deficit that occurred when patients were
      put in standing position. However, all recovered before 3 months postoperatively.
      CONCLUSION: Intrasacral rod fixation appears to be an effective technique to
      correct LSA kyphosis, compensatory hyperlordosis and restore global sagittal
      alignment with a postoperative T1SPi corresponding to the value of the
      asymptomatic subject and achieve fusion. However, it remains a demanding
      technique with high risk of transient neurologic complications.

PMID- 29353327
TI  - Transforaminal endoscopic decompression for thoracic spinal stenosis under local
      anesthesia.
AB  - BACKGROUND: Thoracic spinal stenosis is a common vertebral degenerative disease,
      and treatment remains challenging. In recent years, transforaminal endoscopic
      decompression has been widely used for treating lumbar degenerative diseases.
      However, the efficacy of this procedure for thoracic spinal stenosis has yet to
      be established. Herein, we report a case of thoracic spinal stenosis treated with
      transforaminal endoscopic decompression under local anesthesia. CASE REPORT: An
      88-year-old man presented with a 1-month history of progressive paralysis and
      dysesthesia in the bilateral lower extremities. A diagnosis of thoracic spinal
      stenosis was made, based on physical examination. A two-step percutaneous
      transforaminal endoscopic thoracic decompression was performed for spinal canal
      decompression. Over a follow-up of 1 year, a favorable outcome was noted.
      CONCLUSION: Transforaminal endoscopic decompression is a safe and an effective
      surgical approach for the treatment of thoracic spinal stenosis. For patients
      with thoracic spinal stenosis, accurate diagnosis and elaborate surgical planning
      should be highlighted, and the surgical outcome can be favorable.

PMID- 29353325
TI  - A head-to-tail view of L-selectin and its impact on neutrophil behaviour.
AB  - L-selectin is a type I transmembrane cell adhesion molecule expressed on most
      circulating leukocytes, including neutrophils. Engagement of L-selectin with
      endothelial-derived ligands initiates neutrophil tethering and rolling behaviour
      along luminal walls of post-capillary venules, constituting the first step of the
      multi-step adhesion cascade. There is a large body of evidence to suggest that
      signalling downstream of L-selectin can influence neutrophil behaviour: adhesion,
      migration and priming. This review will cover aspects of L-selectin form and
      function and introduce the "triad of L-selectin regulation", highlighting the
      inextricable links between adhesion, signalling and ectodomain shedding and also
      highlighting the cytosolic proteins that interconnect them. Recent advances in
      how L-selectin impacts priming, transendothelial migration (TEM) and cell
      polarity will also be discussed.

PMID- 29353329
TI  - Correction to: Stigma in the context of pregnancy termination after diagnosis of
      fetal anomaly: associations with grief, trauma, and depression.
AB  - The original version of this article unfortunately incorrectly captured table 4.

PMID- 29353328
TI  - Serum uric acid levels are associated with lupus nephritis in patients with
      normal renal function.
AB  - Uric acid has been recognised as a potential marker of endothelial dysfunction
      and kidney disease but there are scarce data about its importance in systemic
      lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid
      (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal
      function, with and without nephritis. Forty-six female SLE patients were
      consecutively selected and divided in two groups according to renal activity at
      the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n = 18)
      and absence of lupus nephritis (LN-, n = 28). Age-matched healthy women were
      selected (CONTROL, n = 28). Patients with gout, creatinine clearance lower than
      80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and
      clinical data were analysed by appropriate tests. A multivariate analysis was
      performed, and a receiver operating characteristic (ROC) curve was plotted, and
      the area under the curve was calculated to assess the diagnostic strength of UA
      in LN. The mean age was similar among LN+, LN- and CONTROL groups (32.44 +/- 6.09
      vs. 30.68 +/- 5.36 vs. 30.86 +/- 5.00 years, p = 0.52). UA was significantly
      higher in LN+ compared to LN- (5.54 +/- 1.67 vs. 3.65 +/- 1.090 mg/dL, p < 0.001)
      and CONTROL (5.54 +/- 1.67 vs. 3.92 +/- 0.95 mg/dL p < 0.001). Multivariate
      analysis confirmed that high UA was an independent variable related to LN (p <
      0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p
      = 0.00004, CI 95% 0.75-0.96). Lupus nephritis was associated with higher UA.
      Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in
      further studies.

PMID- 29353330
TI  - Leveraging variable sensor spatial acuity with a homogeneous, multi-scale place
      recognition framework.
AB  - Most robot navigation systems perform place recognition using a single-sensor
      modality and one, or at most two heterogeneous map scales. In contrast, mammals
      perform navigation by combining sensing from a wide variety of modalities
      including vision, auditory, olfactory and tactile senses with a multi-scale,
      homogeneous neural map of the environment. In this paper, we develop a multi
      scale, multi-sensor system for mapping and place recognition that combines
      spatial localization hypotheses at different spatial scales from multiple
      different sensors to calculate an overall place recognition estimate. We evaluate
      the system's performance over three repeated 1.5-km day and night journeys across
      a university campus spanning outdoor and multi-level indoor environments,
      incorporating camera, WiFi and barometric sensory information. The system
      outperforms a conventional camera-only localization system, with the results
      demonstrating not only how combining multiple sensing modalities together
      improves performance, but also how combining these sensing modalities over
      multiple scales further improves performance over a single-scale approach. The
      multi-scale mapping framework enables us to analyze the naturally varying spatial
      acuity of different sensing modalities, revealing how the multi-scale approach
      captures each sensing modality at its optimal operation point where a single
      scale approach does not, and enables us to then weight sensor contributions at
      different scales based on their utility for place recognition at that scale.

PMID- 29353331
TI  - Construction of a plasmid vector containing epidermal growth factor receptor and
      C-Jun shRNA.
AB  - The objective of this study was to construct a plasmid vector for EGFR-hm-1 and C
      Junh-825 small interfering RNA (siRNA). EGFR-hm-1 and C-Jun-hm-825
      oligonucleotide fragments were synthesized and short hairpin RNA (shRNA) were
      amplified by PCR. Plasmids were isolated from E. coli TOP10 bacterium by
      restriction enzyme digestion using pst1 and BamH1 and oligonucleotide fragments
      were cloned into the pSilencer plasmid containing the U6 promoter. Recombinant
      clones were generated by transforming JM109 competent cells with plasmid vectors
      containing shRNA molecules. 58 base-paired EGFR-hm-1 and 59 base-paired C-Jun-hm
      825 oligonucleotide fragments were isolated. The fragments were 100% homologous
      with human sequences available on GenBank. The recombinant pSilencer1.0 vector
      containing a 58-bp EGFR-hm-1 and 59-bp C-Jun-hm-825 fragment was constructed.
      These vectors have the potential to be used as treatment to combat skin
      photoaging under UV exposure.

PMID- 29353332
TI  - First-line chemotherapy with S-1 alone or S-1 plus cisplatin for elderly patients
      with advanced gastric cancer: a multicenter propensity score matched study.
AB  - BACKGROUND: Fluoropyrimidine and platinum combination is the standard treatment
      for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine
      monotherapy is commonly used for elderly patients with AGC because of its good
      tolerability. METHODS: In this multicenter retrospective study, we collected
      clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S
      1 plus cisplatin (SP) as the first-line treatment between January 2009 and
      December 2011. Propensity score matched cohorts (PSMC) were used for reducing the
      confounding effects to compare efficacy and safety between the two treatment
      groups. Cox regression analysis was performed to clarify the prognostic factors.
      RESULTS: PSMC (n = 109 in each group) were selected from among 444 eligible
      patients (S-1 group, 210; SP group, 234); the S-1 group included more patients
      deemed unfit for intensive chemotherapy than the SP group (e.g., higher age,
      poorer PS, poor renal function). In the PSMC, patients' characteristics were
      comparable between groups, except the male ratio (S-1 group, 64.2%; SP group,
      77.1%; p = 0.04). No significant differences were observed in either overall
      survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR
      1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were
      more frequent in the SP group than in the S-1 group (p < 0.001 each). CONCLUSION:
      Our findings do not support the survival benefit of SP over S-1 in elderly
      patients with AGC. We are now conducting a prospective comparative study to
      optimize treatment strategy and explore applicability of the geriatric assessment
      for these patients.

PMID- 29353335
TI  - Leveraging model-informed approaches for drug discovery and development in the
      cardiovascular space.
AB  - Cardiovascular disease remains a significant global health burden, and
      development of cardiovascular drugs in the current regulatory environment often
      demands large and expensive cardiovascular outcome trials. Thus, the use of
      quantitative pharmacometric approaches which can help enable early Go/No Go
      decision making, ensure appropriate dose selection, and increase the likelihood
      of successful clinical trials, have become increasingly important to help reduce
      the risk of failed cardiovascular outcomes studies. In addition, cardiovascular
      safety is an important consideration for many drug development programs, whether
      or not the drug is designed to treat cardiovascular disease; modeling and
      simulation approaches also have utility in assessing risk in this area. Herein,
      examples of modeling and simulation applied at various stages of drug
      development, spanning from the discovery stage through late-stage clinical
      development, for cardiovascular programs are presented. Examples of how modeling
      approaches have been utilized in early development programs across various
      therapeutic areas to help inform strategies to mitigate the risk of
      cardiovascular-related adverse events, such as QTc prolongation and changes in
      blood pressure, are also presented. These examples demonstrate how more informed
      drug development decisions can be enabled by modeling and simulation approaches
      in the cardiovascular area.

PMID- 29353333
TI  - Frailty Assessment in Heart Failure: an Overview of the Multi-domain Approach.
AB  - PURPOSE OF REVIEW: The study aims (1) to provide a contemporary description of
      frailty assessment in heart failure and (2) to provide an overview of multi
      domain frailty assessment in heart failure. RECENT FINDINGS: Frailty assessment
      is an important predictive measure for mortality and hospitalisation in
      individuals with heart failure. To date, there are no frailty assessment
      instruments validated for use in heart failure. This has resulted in significant
      heterogeneity between studies regarding the assessment of frailty. The most
      common frailty assessment instrument used in heart failure is the Frailty
      Phenotype which focuses on five physical domains of frailty; the appropriateness
      a purely physical measure of frailty in individuals with heart failure who
      frequently experience decreased exercise tolerance and shortness of breath is yet
      to be determined. A limited number of studies have approached frailty assessment
      using a multi-domain view which may be more clinically relevant in heart failure.
      There remains a lack of consensus regarding frailty assessment and an absence of
      a validated instrument in heart failure. Despite this, frailty continues to be
      assessed frequently, primarily for research purposes, using predominantly
      physical frailty measures. A more multidimensional view of frailty assessment
      using a multi-domain approach will likely be more sensitive to identifying at
      risk patients.

PMID- 29353336
TI  - Serum Free Light Chains in CVID-a Marker for Differential Diagnosis.

PMID- 29353337
TI  - A retrospective analysis of 5-fluorouracil plus cisplatin as first-line
      chemotherapy in the recent treatment strategy for patients with metastatic or
      recurrent esophageal squamous cell carcinoma.
AB  - BACKGROUND: Patients with metastatic or recurrent esophageal squamous cell
      carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first
      line chemotherapy regimen for these patients has been the combination of 5
      fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line
      chemotherapy for ESCC have not been clarified. METHODS: A total of 187 patients
      with metastatic or recurrent esophageal ESCC treated with CF at the National
      Cancer Center Hospital between January 2001 and December 2012 were enrolled in
      the study. The CF regimen comprised cisplatin (80 mg/m2) administered on day 1
      and 5-fluorouracil (800 mg/m2) administered continuously on days 1-5, every 4
      weeks. Multivariate Cox regression analysis was used to determine the potential
      prognostic factors. RESULTS: The median age of the patients was 62 (range 34-84)
      years. Metastasis and recurrence occurred in 116 and 71 of these patients,
      respectively. The overall response rate was 37.2%, with median progression-free
      and overall survival times of 4.8 and 10.4 months, respectively. In the
      multivariate analysis, higher serum C-reactive protein level and lower serum
      albumin level at the time of CF treatment initiation and number of metastatic
      sites were identified as independent prognostic factors for survival.
      CONCLUSIONS: The results of this study corroborate previous findings on the
      efficacy of CF and will aid physicians in clinical decision-making and individual
      patient risk stratification, as well as in the further development of
      chemotherapy regimens.

PMID- 29353338
TI  - The Use of Infant Confinement Equipment in Community-Based Child Care Centers: An
      Analysis of Centers Participating in a Statewide Quality Rating and Improvement
      System.
AB  - Objectives Although infants increasingly spend time in community-based child care
      centers, little attention has been paid to their physical activity experiences
      while in group care. In particular, the use of devices to restrict infant
      mobility, such as bouncy seats, high chairs, cribs, and stationary activity
      centers, has received little attention in the physical activity literature. The
      current study examines the presence and use of these confinement devices in
      infant classrooms. Methods A secondary analysis of observational data in child
      care centers participating in Delaware's Quality Rating and Improvement System
      was conducted. Quality assessment observations were coded for the use of
      confinement devices and the actual amount of time the confinement device was
      employed per child. The sample consisted of 38 infant classrooms serving a total
      of 162 infants in the statewide system. Results Findings suggest a high level of
      utilization of confinement devices in infant child care classrooms with each
      classroom averaging three pieces of equipment used during the observations and
      22% of observed children being confined 30 min or longer during the observation
      period. Conclusions for Practice The reliance on confinement devices in group
      child care is a potential concern in the quest to prevent childhood obesity by
      ensuring adequate physical activity and mobility for infants in group care
      settings. More research is needed to understand the implications of the use of
      confinement devices on physical activity in group care settings.

PMID- 29353339
TI  - Chronic pain, discomfort, quality of life and impact on sex life after open
      inguinal hernia mesh repair: an expertise-based randomized clinical trial
      comparing lightweight and heavyweight mesh.
AB  - PURPOSE: There is a paucity of high-quality evidence concerning mesh choice in
      open inguinal hernia repair. Using an expertise-based randomized clinical trial
      design, we aimed to evaluate the postoperative impact of two different mesh types
      on pain and discomfort, quality of life and sex life. METHODS: In two regional
      hospitals, male patients with primary inguinal hernia were randomized to one of
      two groups of surgeons that performed the Lichtenstein operation. One group of
      surgeons used a heavyweight polypropylene mesh (90 g/m2, BardTM Flatmesh, Davol)
      while the second group employed a lightweight mesh (28 g/m2, ULTRAPROTM,
      Ethicon). Follow-up data were collected by questionnaires and outpatient visits
      in the range of 1-3 years after surgery. RESULTS: Some 412 patients were
      randomized and 363 patients were analysed. There was no difference in pain
      between groups after surgery but a statistically significant difference
      concerning awareness of a groin lump and groin discomfort, favouring the
      lightweight group 1 year after surgery. No differences in quality of life between
      groups could be detected but both groups had a substantially better quality of
      life postoperatively, as compared to before surgery. In the analysis of impact on
      sex life, no differences between mesh groups were found. CONCLUSION: The
      Lichtenstein operation performed for primary inguinal hernia improves quality of
      life for most of the male patients, independently of the type of mesh used. The
      lightweight mesh group experienced less awareness of a groin lump and groin
      discomfort 1 year postoperatively. ClinicalTrials.gov Identifier: NCT00451893.

PMID- 29353340
TI  - Deep Learning and Computational Neuroscience.

PMID- 29353341
TI  - Field of View Normalization in Multi-Site Brain MRI.
AB  - Multi-site brain MRI analysis is needed in big data neuroimaging studies, but
      challenging. The challenges lie in almost every analysis step including skull
      stripping. The diversities in multi-site brain MR images make it difficult to
      tune parameters specific to subjects or imaging protocols. Alternatively, using
      constant parameter settings often leads to inaccurate, inconsistent and even
      failed skull stripping results. One reason is that images scanned at different
      sites, under different scanners or protocols, and/or by different technicians
      often have very different fields of view (FOVs). Normalizing FOV is currently
      done manually or using ad hoc pre-processing steps, which do not always
      generalize well to multi-site diverse images. In this paper, we show that (a) a
      generic FOV normalization approach is possible in multi-site diverse images; we
      show experiments on images acquired from Philips, GE, Siemens scanners, from
      1.0T, 1.5T, 3.0T field of strengths, and from subjects 0-90 years of ages; and
      (b) generic FOV normalization improves skull stripping accuracy and consistency
      for multiple skull stripping algorithms; we show this effect for 5 skull
      stripping algorithms including FSL's BET, AFNI's 3dSkullStrip, FreeSurfer's HWA,
      BrainSuite's BSE, and MASS. We have released our FOV normalization software at
      http://www.nitrc.org/projects/normalizefov .

PMID- 29353342
TI  - Genetic analysis of 17 Y-STR loci from 1026 individuals of Han populations in
      Jilin Province, Northeast China.
AB  - In this study, 17 Y-chromosomal short tandem repeats (Y-STRs) were analyzed in
      1026 male individuals of Han populations in Changchun City, Jilin Province,
      Northeast China. The haplotype diversity is 0.99892. The Changchun Han population
      is close to most Han populations and different from most other minority
      populations of China. Additionally, the Changchun Han show more affiliations with
      Han populations in North and Northeast China. These data provide a reference for
      the Y-STR database in Jilin Province, and they may be valuable for population
      genetic analysis.

PMID- 29353343
TI  - The decreased expression of Stat3 and p-Stat3 in preeclampsia-like rat placenta.
AB  - This study aims to investigate the expression of Stat3 and p-Stat3 in the
      placenta of a preeclampsia-like rat model induced by Nomeganitro-L-arginine
      methyl ester (L-NAME). Two-to three-month-old (20 males, 40 females) Sprague
      Dawley rats were used in this study. After conception was confirmed by vaginal
      smears, on the thirteenth day of pregnancy, the animals were allocated into two
      groups: control (0.9% NaCl administered) group and L-NAME (75 mg/kg) group. After
      the treatment of L-NAME, there was a significant increase in systolic blood
      pressure (SBP) levels in the L-NAME group (148.5 +/- 5.71 mmHg) on day 21
      compared to the SBPs in the control group (117.5 +/- 4.57 mmHg) (P < 0.001).
      There was also an increase in total proteinuria on day 21 in the L-NAME group
      (766.57 +/- 17.7 mg/L), when compared to the control group (459.89 +/- 20.1 mg/L)
      (P < 0.001). Moreover, we also found a decrease in fetal numbers and fetal weight
      in the PE group in comparison to the control group. After the rats were
      sacrificed, the placentas were obtained from both groups. We found that the L
      NAME group exhibited fewer placentas compared with the control group.
      Furthermore, the immunohistochemistry (IHC) and Western blot results showed that
      decreased expression of Stat3 and p-Stat3 were detected in the placenta of the
      preeclampsia-like rat model compared to Stat3 and p-Stat3 in the control group.
      We found the expression and activation of Stat3 and p-Stat3 were decreased in the
      placenta of the L-NAME-induced preeclampsia rat model.

PMID- 29353344
TI  - Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes.
AB  - PURPOSE: To study the safety and biocompatibility of Laponite clay (LAP) within
      an intravitreal and suprachoroidal administration in rabbit eyes. METHODS: Thirty
      two New Zealand albino rabbits were divided into two experimental groups to test
      intravitreal (IVT group) and suprachoroidal (SCS group) administration of a 100
      MUl and 50-MUl Laponite suspension respectively. Following injection, the eyes
      were monitored by ocular tonometry, slit-lamp eye examination and indirect
      ophthalmoscopy, at 24 h, 1, 4, 12, and 14 weeks post administration. Histological
      examination was also performed to determine whether any ocular pathological
      change had occurred. Throughout the study, LAP presence in vitreous was estimated
      by complexometric titration with ethylenediaminetetraacetic acid (EDTA), taking
      advantage of the Laponite high content of magnesium ions. RESULTS: Neither
      significant differences in the intraocular pressure, nor relevant ocular
      complications were found in the two experimental groups after LAP administration.
      The histology of the retina remained unchanged. LAP presence in vitreous could be
      indirectly confirmed by complexometric titration until 14 weeks post
      administration in eyes of IVT group. CONCLUSION: Laponite could be considered as
      a vehicle for potential clinical use in ocular drug administration, due to its
      proven ocular biocompatibility and its transparency in gel state.

PMID- 29353345
TI  - Detailed analysis of retinal morphology in patients with diabetic macular edema
      (DME) randomized to ranibizumab or triamcinolone treatment.

PMID- 29353346
TI  - Singleplex quantitative real-time PCR for the assessment of human mitochondrial
      DNA quantity and quality.
AB  - Mitochondrial DNA (mtDNA) can provide a means for forensic identity testing when
      genotyping of nuclear DNA (nuDNA) targets is not possible due to degradation or
      lack of template. For degraded samples, an indication of the quantity and quality
      of mtDNA is essential to allow selection of appropriately sized targets for
      hypervariable region (HVR) analysis, which may conserve sample and resources.
      Three human-specific mtDNA targets of increasing length (86, 190 and 452 base
      pairs) were amplified by singleplex quantitative real-time PCR (qPCR), capable of
      providing an index of mtDNA degradation from fragment length information.
      Quantification was achieved by preparation of a standard curve for each target,
      using a purified mtDNA standard containing all three targets of interest, which
      produced a linear, accurate and precise result from 1*108 to 10 copies. These
      novel assays demonstrated excellent sensitivity, specificity and reproducibility
      in line with the minimum information for qPCR experiments (MIQE) guidelines.
      Further, a separate inhibition control reaction was included to guide sample
      clean-up and ensure the validity of degradation assays. This protocol assists the
      selection and analysis of appropriately sized targets to maximize the chance of
      obtaining an informative result in downstream assays like sequencing.

PMID- 29353347
TI  - Serum pepsinogen levels indicate the requirement of upper gastrointestinal
      endoscopy among Group A subjects of ABC classification: a multicenter study.
AB  - BACKGROUND: ABC classification has been used to assess the risk for gastric
      cancer. The current problem of ABC classification is that Group A contains
      individuals with current and past H. pylori infection. The aims of this study
      were to assesse the proportion of current and past infection in Group A and to
      establish a criteria for the identification of subjects with past infection from
      Group A subjects with negative results of urea breath test (UBT) and/or stool
      antigen test. METHODS: 201 subjects classified into Group A received UBT and/or
      stool antigen test, and also subsequent upper gastrointestinal endoscopy. The
      subjects were classified by the status of H. pylori infection defined by
      endoscopic findings. Levels of pepsinogen (PG) I, PG II and PG I/II ratio were
      compared between the groups, and receiver operating characteristic curves were
      constructed to extract the corresponding cutoff values. RESULTS: 22 subjects were
      tested positive by UBT and/or stool antigen test. Endoscopic images of 157 out of
      179 subjects were studied. 15 of the subjects were regarded to have past H.
      pylori infection. The optimal cut-off value of PG I and PG I/II ratio for the
      determination of past H. pylori infection were <= 31.2 ng/mL and <= 4.6,
      respectively. CONCLUSIONS: Approximately 20% of Group A subjects have current or
      past H. pylori infection. Addition of UBT and/or stool antigen test can identify
      current but not past infection. Serum PG levels would be useful to identify
      subjects with past H. pylori infection.

PMID- 29353348
TI  - Insulin receptor substrate-4 is overexpressed in colorectal cancer and promotes
      retinoblastoma-cyclin-dependent kinase activation.
AB  - BACKGROUND: Insulin receptor substrate 4 (IRS-4) is an adaptor protein for which
      new evidence suggests plays a role in tumour promotion. METHODS: We described
      nuclear IRS-4 in RKO colon cancer cell lines in biopsies of patients with
      colorectal cancer (CRC) (n = 20) and in matched adjacent normal colorectal (MANC)
      tissue (n = 20). RESULTS: Treatment with physiological doses of IGF-1 promoted
      nuclear influx of IRS-4 from cellular cytosol in RKO cells. When exogenous IRS-4
      was overexpressed in RKO cells, there was an increase in cyclin D1, cyclin E,
      E2F1, pRB Ser 809/811 and pRB Ser 705 levels compared with the empty vector
      transfected cells. Some of these changes returned to control values after
      wortmannin treatment. Subcellular fractionation showed an overexpression of IRS-4
      in the cytoplasm, membrane, and nuclei of tumour samples, whereas the levels of
      the protein were barely detectable in the three compartments of normal samples.
      Immunohistochemical studies showed positive nuclear IRS-4 staining in over 74% of
      the tumour cells. IRS-4 was strongly overexpressed in tumoural tissues from CRC
      patients compared to MANC tissues. The up-regulation of IRS-4 in CRC samples
      correlated significantly with the increase of several G1 checkpoint proteins
      including cyclin D1 (r = 0.6662), Rb (r = 0.7779), pRb Serine 809/811 (r =
      0.6864), pRb serine 705 (r = 0.6261) and E2F1 (r = 0.8702). CONCLUSIONS: Taken
      together, our findings suggest that IRS-4 promotes retinoblastoma-cyclin
      dependent kinase activation and it may serve as a pharmacological target since
      its expression is very low in normal tissue, including colonic epithelium.

PMID- 29353349
TI  - Daclatasvir: A Review of Preclinical and Clinical Pharmacokinetics.
AB  - Daclatasvir is a first-in-class, highly selective, hepatitis C virus, non
      structural protein 5a polymerase replication complex inhibitor with picomolar
      potency and broad genotypic coverage in vitro. Daclatasvir undergoes rapid
      absorption, with a time to reach maximum plasma concentration of 1-2 h and an
      elimination half-life of ~ 10 to 14 h observed in single-ascending dose studies.
      Steady state was achieved by day 4 in multiple-ascending dose studies.
      Daclatasvir can be administered without regard to food or pH modifiers.
      Daclatasvir exposure is similar between healthy subjects and subjects infected
      with hepatitis C virus. Intrinsic factors such as age, race, or sex do not impact
      daclatasvir exposure. No dose adjustment is necessary for patients with any
      degree of hepatic or renal impairment. Daclatasvir has low-to-moderate clearance
      with the predominant route of elimination via cytochrome P450 3A4-mediated
      metabolism and P-glycoprotein excretion and intestinal secretion. Renal clearance
      is a minor route of elimination for daclatasvir. As a result, the dose of
      daclatasvir should be reduced from 60 to 30 mg once daily when co-administered
      with strong inhibitors of cytochrome P450 3A4. No dose adjustment is required
      when daclatasvir is co-administered with moderate inhibitors of cytochrome P450
      3A4. The dose of daclatasvir should be increased from 60 to 90 mg once daily when
      co-administered with moderate inducers of cytochrome P450 3A4. Co-administration
      of daclatasvir with strong inducers of cytochrome P450 3A4 is contraindicated.
      Concurrent medications with inhibitory effects on P-glycoprotein without
      concurrent inhibition of cytochrome P450 3A4 are unlikely to cause marked changes
      in daclatasvir exposure, as the clearance of daclatasvir is through both
      cytochrome P450 3A4 and P-glycoprotein. The potential for daclatasvir to affect
      the pharmacokinetics of concomitantly administered drugs that are substrates of
      the cytochrome P450 enzyme system is low. In vitro, daclatasvir is a weak-to
      moderate inhibitor of transporters including organic cation transporter 1, P
      glycoprotein, organic transporting polypeptide 1B1, organic transporting
      polypeptide 1B3, and breast cancer resistance protein, although in clinical
      studies, daclatasvir has not altered the pharmacokinetics of concomitantly
      administered drugs that are substrates of these transporters to an appreciable
      degree, except for rosuvastatin. In summary, daclatasvir is a hepatitis C virus,
      non-structural protein 5a-selective inhibitor with a well-characterized
      pharmacokinetic profile that forms part of potent and well-tolerated all-oral
      treatment regimens for chronic hepatitis C virus infection.

PMID- 29353350
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low
      density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL
      receptor on hepatic cells. Evolocumab is a human monoclonal immunoglobulin G2
      that binds specifically to human PCSK9 to reduce LDL-C. Evolocumab exhibits
      nonlinear kinetics as a result of binding to PCSK9. Elimination is predominantly
      through saturable binding to PCSK9 at lower concentrations and a nonsaturable
      proteolytic pathway at higher concentrations. The effective half-life of
      evolocumab is 11-17 days. The pharmacodynamic effects of evolocumab on PCSK9 are
      rapid, with maximum suppression within 4 h. At steady state, peak reduction of
      LDL-C occurs approximately 1 week after a subcutaneous dose of 140 mg every 2
      weeks (Q2W) and 2 weeks after a subcutaneous dose 420 mg once monthly (QM), and
      returns towards baseline over the dosing interval. In several clinical studies,
      these doses of evolocumab reduced LDL-C by approximately 55-75% compared with
      placebo. Evolocumab also reduced lipoprotein(a) [Lp(a)] levels and improved those
      of other lipids in clinical studies. No clinically meaningful differences in
      pharmacodynamic effects on LDL-C were observed in adult subjects regardless of
      mild/moderate hepatic impairment, renal impairment or renal failure, body weight,
      race, sex, or age. No clinically meaningful differences were observed for the
      pharmacodynamic effects of evolocumab on LDL-C between patients who received
      evolocumab alone or in combination with a statin, resulting in additional
      lowering of LDL-C when evolocumab was combined with a statin. No dose adjustment
      is necessary based on patient-specific factors or concomitant medication use.

PMID- 29353352
TI  - Unilateral isolated hypoglossal neuropathy associated to jugular paraganglioma.

PMID- 29353351
TI  - The multiple roles of titin in muscle contraction and force production.
AB  - Titin is a filamentous protein spanning the half-sarcomere, with spring-like
      properties in the I-band region. Various structural, signaling, and mechanical
      functions have been associated with titin, but not all of these are fully
      elucidated and accepted in the scientific community. Here, I discuss the primary
      mechanical functions of titin, including its accepted role in passive force
      production, stabilization of half-sarcomeres and sarcomeres, and its
      controversial contribution to residual force enhancement, passive force
      enhancement, energetics, and work production in shortening muscle. Finally, I
      provide evidence that titin is a molecular spring whose stiffness changes with
      muscle activation and actin-myosin-based force production, suggesting a novel
      model of force production that, aside from actin and myosin, includes titin as a
      "third contractile" filament. Using this three-filament model of sarcomeres, the
      stability of (half-) sarcomeres, passive force enhancement, residual force
      enhancement, and the decrease in metabolic energy during and following eccentric
      contractions can be explained readily.

PMID- 29353354
TI  - Relationship among aqueous copper half-lives and responses of Pimephales promelas
      to a series of copper sulfate pentahydrate concentrations.
AB  - Copper algaecide exposures in situ are often of shorter duration than exposures
      for static toxicity experiments because aqueous concentrations in situ dissipate
      as a function of site-specific fate processes. Consequently, responses of
      organisms to static copper exposures may overestimate effects following in situ
      exposures. To understand the role of exposure duration for altering responses,
      Pimephales promelas survival was compared following static (96 h) and pulse (1.5,
      4, 8, and 15 h half-lives) exposures of CuSO4*5H2O. Copper concentrations sorbed
      by fry indicated a consequence of different exposures. Responses of P. promelas
      to static exposures resulted in 96 h LC50s of 166 ugCu/L (95% confidence interval
      [CI], 142-189 ugCu/L) as soluble copper and 162 ugCu/L (CI, 140-183 ugCu/L) as
      acid soluble copper. Relative to static 96 h LC50s, exposures with half-lives of
      1.5, 4 and 8 h resulted in LC50s 10, 3 and 2 times greater, respectively, for
      responses measured 96 h after exposure initiation. Copper concentrations
      extracted from fry exposed for 1.5, 4 and 8 h half-lives were less than the
      static experiment. However, copper sorbed by fry in the 15 h half-life experiment
      was not different than the static experiment. The relationship between 96 h LC50
      and 1/half-life was expressed using the equations y = 116 + 1360 * (R2 = 0.97)
      for soluble copper and y = 147 + 1620 * (R2 = 0.98) for acid soluble copper.
      Incorporation of exposure duration for predictions of P. promelas responses to
      copper pulse exposures increases prediction accuracy by an order of magnitude.

PMID- 29353353
TI  - Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke.
AB  - CD4+CD25+ regulatory T (Treg) cells and Th17 cells play important roles in
      peripheral immunity. Immune responses are main elements in the pathogenesis of
      ischemic stroke (IS). The contribution of Th17 cells in IS patients has not been
      proved, and whether the balance of Treg/Th17 cells is changed in IS patients
      remains unidentified. In the present study, we studied Th17 and Treg cell
      frequency, cytokine secretion, expression of transcription factors, and microRNAs
      related to Th17 and Treg cells differentiation, which is compared between IS
      patients and control group. Thirty patients with IS and 30 individuals as control
      group were enrolled in this study. The frequency of Th17 and Treg lymphocytes,
      the expression of transcription factors and microRNAs related to these cells, and
      the serum levels of associated cytokines were assessed by flow cytometry, real
      time PCR, and ELISA, respectively. A significant reduction in proportion of
      peripheral Treg cell frequency and the levels of TGF-beta and FOXP3 expression
      were observed in patients with IS compared with controls, while the proportions
      of Th17 were increased dramatically, and these effects were along with increases
      in the levels of IL-17A and RORgammat expression in IS patients. The levels of
      mir-326 and mir-106b-25 expression were increased in patients with IS. These
      studies suggest that the increase in proportion of Th17 cells and decrease in
      Treg cells might contribute to the pathogenesis of IS. Manipulating the balance
      between Tregs and Th17 cells might be helpful for the treatment of IS.

PMID- 29353355
TI  - Cerebrospinal fluid biomarkers profile of idiopathic normal pressure
      hydrocephalus.
AB  - Idiopathic normal pressure hydrocephalus (iNPH) is a disabling neurological
      disorder whose potential treatability is significantly limited by diagnostic
      uncertainty. In fact, typical clinical presentation occurs at late phases of
      disease, when CSF shunting could be ineffective. In recent years, measurement of
      different CSF proteins, whose concentration directly reflects neuropathological
      changes of CNS, has significantly improved both diagnostic timing and accuracy of
      neurodegenerative disease. Unfortunately iNPH lacks neuropathological hallmarks
      allowing the identification of specific disease biomarkers. However,
      neuropathology of iNPH is so rich and heterogeneous that many processes can be
      tracked in CSF, including Alzheimer's disease core pathology, subcortical
      degeneration, neuroinflammation and vascular dysfunction. Indeed, a huge number
      of CSF biomarkers have been analyzed in iNPH patients, but a unifying profile has
      not been provided yet. In this brief survey, we thus attempted to summarize the
      main findings in the field of iNPH CSF biomarkers, aimed at outlining a synthetic
      model. Although defined cut-off values for biomarkers are not available, a better
      knowledge of CSF characteristics may definitely assist in diagnosing the disease.

PMID- 29353356
TI  - Generation of shrimp waste-based dispersant for oil spill response.
AB  - In this study, shrimp waste was enzymatically hydrolyzed to generate a green
      dispersant and the product was tested for crude oil dispersion in seawater. The
      hydrolysis process was first optimized based on the dispersant effectiveness (DE)
      of the product. The functional properties of the product were identified
      including stability, critical micelle concentration, and emulsification activity.
      Water was confirmed as a good solvent for dispersant generation when compared
      with three chemical solvents. The effects of salinity, mixing energy, and
      temperature on the dispersion of the Alaska North Slope (ANS) crude oil were
      examined. Microtox acute toxicity test was also conducted to evaluate the
      toxicity of the produced dispersant. In addition, DE of the product on three
      different types of crude oil, including ANS crude oil, Prudhoe Bay crude oil
      (PBC), and Arabian Light crude oil (ALC) was compared with that of the Corexit
      9500, respectively. The research output could lead to a promising green solution
      to the oil spill problem and might result in many other environmental
      applications.

PMID- 29353357
TI  - Heath risk among pesticide sellers in Bamenda (Cameroon) and peripheral areas.
AB  - In Bamenda and peripheral zones, studies have been focused on the effects of
      pesticides on farmers (pesticide users) while nothing has been done to assess the
      exposure of sellers to pesticides. This study aimed at evaluating the exposure of
      pesticide sellers in the same area. Thirty-two questionnaires were administered
      to 32 pesticide sellers systematically selected, and chi-square was used for
      statistical analysis. From each shop, a respondent was chosen among the workers
      according to its daily time spent in the workplace. The results showed that there
      is similarity between sellers in Bamenda and peripheral area; one active
      ingredient (metalaxyl) and one formulation (beauchamp) sold are not registered;
      throat irritation, headaches, fatigue, skin irritation, eye irritation, and
      difficulty in breathing with more cases of nose irritation were symptoms
      observed; pesticides are stored either in the shops or in warehouses; safety
      measures generally applied are sitting outside the shop, taking medicated
      charcoal and the use of protective clothing; 56% have less than 5 years
      experience. Permanent pesticide sellers are then exposed to chronic intoxication
      in Bamenda and neighboring zones. Employers should make use of protective
      clothing in their shops when manipulating pesticides in the application of safety
      measures.

PMID- 29353358
TI  - Modeling the impact of transport energy consumption on CO2 emission in Pakistan:
      Evidence from ARDL approach.
AB  - The objective of this research is to examine the relationship between transport
      energy consumption, economic growth, and carbon dioxide emission (CO2) from
      transport sector incorporating foreign direct investment and urbanization. This
      study is carried out in Pakistan by applying autoregressive distributive lag
      (ARDL) and vector error correction model (VECM) over 1990-2015. The empirical
      results indicate a strong significant impact of transport energy consumption on
      CO2 emissions from the transportation sector. Furthermore, foreign direct
      investment also contributes to CO2 emission. Interestingly, the impact of
      economic growth and urbanization on transport CO2 emission is statistically
      insignificant. Overall, transport energy consumption and foreign direct
      investment are not environmentally friendly. The new empirical evidence from this
      study provides a complete picture of the determinants of emissions from the
      transport sector and these novel findings not only help to advance the existing
      literature but also can be of special interest to the country's policymakers. So,
      we urge that government needs to focus on promoting the energy efficient means of
      transportation to improve environmental quality with less adverse influence on
      economic growth.

PMID- 29353359
TI  - The effects of rainfall regimes and terracing on runoff and erosion in the Three
      Gorges area, China.
AB  - Changes in natural rainfall regimes have taken place and are expected to become
      more pronounced in future decades. These changes are also likely to be
      accompanied by changes in crop management practices. The main purpose of this
      study was to analyze runoff and soil loss in relation to rainfall regimes and
      terracing in the Three Gorges area, China. Based on 10 years of field observation
      and k-mean clusters, 101 rainfall events were grouped into three rainfall
      regimes. Rainfall regime I was the group of events with strong rainfall
      intensity, high frequency, and short duration. Rainfall regime III consisted of
      events with low intensity, long duration, and high rainfall amount. Rainfall
      regime II was the aggregation of events of high intensity and amount, and less
      frequent occurrence. The results showed that event runoff coefficients were not
      significantly different among rainfall regimes. However, the average soil erosion
      rates in rainfall regimes I and II were significantly higher than that in regime
      III. The average erosion rates under rainfall regimes I, II, and III were 21.6,
      39.7, and 9.8 g m-2, respectively. The effect of rainfall regime on soil erosion
      also was changed by terracing. On unterraced cropland, soil erosion rate in
      rainfall regime I is significantly higher than that in regime III. However, the
      situation did not exist in unterraced orchard. Terracing significantly reduced
      runoff and soil erosion, and compensated the effects of rainfall regime on soil
      erosion, which indicated that runoff and erosion in terraced system may be little
      influenced by climate change. Based on these results, it was suggested more
      attention should be paid to the timing of rainfall events in relation to crop
      development and the high erosion on unterraced citrus orchard to control soil
      erosion in this area.

PMID- 29353362
TI  - Is it Suitable for a Journal to Bid for Publishing a Review That is Likely to be
      Highly Cited?
AB  - By following a recently published paper entitled "The effect of publishing a
      highly cited paper on a journal's impact factor: a case study of the Review of
      Particle Physics" in Learned Publishing, we argue that it is not suitable for
      journals to bid for the right to publish a review that is likely to be highly
      cited. A few suggestions are also provided to deal with the special case of the
      Review of Particle Physics phenomenon.

PMID- 29353361
TI  - Liming induces carbon dioxide (CO2) emission in PSB inoculated alkaline soil
      supplemented with different phosphorus sources.
AB  - Agricultural land is a major sink of global organic carbon (C). Its suitable
      management is crucial for improving C sequestration and reducing soil CO2
      emission. Incubation experiments were performed to assess the impact of phosphate
      solubilizing bacterial (PSB) inoculation (inoculated and uninoculated) and soil
      calcification (4.78, 10, 15, and 20% crushed CaCO3) with phosphorus (P) sources
      [single superphosphate (SSP), rock phosphate (RP), farm yard manure (FYM), and
      poultry manure (PM)] in experiment 1 and with various rates of PM (4, 8, and 12
      kg ha-1) in experiment 2 on cumulative soil respiration. These experiments were
      arranged in three factorial, complete randomize design (CRD) with three
      replications. Interactively, lime with P sources (at day 1 and 3) and lime with
      PSB (at day 1) significantly expedited soil respiration. Mainly, PSB inoculation,
      liming, PM fertilization, and its various rates significantly enhanced soil
      respiration with time over control/minimum in alkaline soil at all incubation
      periods. Higher CO2 emission was detected in soil supplemented with organic P
      sources (PM and FYM) than mineral sources (SSP and RP). CO2 emission was noted to
      increase with increasing PM content. Since liming intensified CO2 discharge from
      soil, therefore addition of lime to an alkaline soil should be avoided; instead,
      integrated approaches must be adopted for P management in alkaline calcareous
      soils for climate-smart agriculture.

PMID- 29353363
TI  - The Implications of Using Internet Search Engines in Structured Scientific
      Reviews.

PMID- 29353360
TI  - In situ monitoring of the Sinos River, southern Brazil: water quality parameters,
      biomarkers, and metal bioaccumulation in fish.
AB  - The Sinos River is an important water supply in Southern Brazil and receives
      industrial, agricultural, and domestic effluents which may affect aquatic biota.
      Water physicochemical and microbiological analyses, biomarker responses (scaled
      mass index (SMI), gill histopathology, and micronucleus and nuclear abnormality
      (MN and NA) frequencies), and metal bioaccumulation in muscle were assessed in
      the fish species Bryconamericus iheringii (Characidae) captured at three sampling
      sites (S1, S2, and S3) in four sampling periods. The mean values of five
      parameters (total phosphorus, thermotolerant coliforms, aluminum, iron, and lead)
      exceeded the limits established by the Brazilian legislation at the three
      sampling sites. Although physicochemical analysis indicated higher impacts at S3,
      in some samples, significantly higher MN frequencies and bioaccumulation of
      manganese in fish muscle were observed at S1, whereas low SMI and higher
      concentrations of aluminum and zinc in fish muscle were found at S2.
      Histopathological alterations in gills were observed in fish collected at the
      three sampling sites; however, no spatial differences were observed, indicating
      similar environmental conditions with respect to this biomarker. Moreover,
      temporal variation of biomarker responses and metal bioaccumulation were found at
      all sampling sites. Furthermore, the consumption of fish from the Sinos River
      should be avoided given the concentrations of chromium (all samples), cadmium,
      and lead in fish muscle above the threshold for safe human consumption.

PMID- 29353364
TI  - Testosterone and Proactive-Reactive Aggression in Youth: the Moderating Role of
      Harsh Discipline.
AB  - This study tests a biosocial model of the link between testosterone and proactive
      reactive aggression in youth at varying levels of harsh discipline. Given that
      proactive aggression is used to gain power and status and the importance of
      social learning in its formation, we hypothesized that testosterone would be
      associated with proactive aggression at higher levels of harsh discipline, and
      that this relationship would be more pronounced in boys than girls. Participants
      (n = 445; 50% male; M age = 11.92 years; 80% African-American) and their
      caregivers completed questionnaires including demographics, conflict tactics, and
      proactive-reactive aggression. Youth also provided a saliva sample for
      testosterone. Analyses revealed an interaction between testosterone and harsh
      discipline on proactive aggression in both boys and girls, and an interaction
      between testosterone and harsh discipline on reactive aggression in boys only.
      For those experiencing high levels of harsh discipline, testosterone was
      positively associated with proactive aggression, with the magnitude of the
      association increasing as harsh discipline increased. For below average levels of
      harsh discipline, there were protective effects of high testosterone for boy's
      reactive aggression and for girl's proactive aggression. The findings support
      basic tenets of the biosocial model which suggest that links between testosterone
      and aggressive behavior are dependent on contextual forces, highlighting the
      complex relationship between hormones, social context, and aggression. Novel
      findings include protective effects of high testosterone for those exposed to low
      levels of harsh discipline. Findings are discussed in light of the context
      contingency effect and also within the differential susceptibility framework.

PMID- 29353365
TI  - 8TH SRCA SYMPOSIUM ON THE CEREBELLUM: FROM DEVELOPMENT TO DISEASE : RADY FACULTY
      OF HEALTH SCIENCES, UNIVERSITY OF MANITOBA, WINNIPEG, MB, CANADA, MAY 24-26,
      2017.

PMID- 29353368
TI  - Detailed information about chemotherapy in breast control arm might affect
      cognitive sequelae compared with endocrine therapy patients.

PMID- 29353367
TI  - Surveillance for cancer recurrence in long-term young breast cancer survivors
      randomly selected from a statewide cancer registry.
AB  - PURPOSE: This study examined clinical breast exam (CBE) and mammography
      surveillance in long-term young breast cancer survivors (YBCS) and identified
      barriers and facilitators to cancer surveillance practices. METHODS: Data
      collected with a self-administered survey from a statewide, randomly selected
      sample of YBCS diagnosed with invasive breast cancer or ductal carcinoma in situ
      younger than 45 years old, stratified by race (Black vs. White/Other).
      Multivariate logistic regression models identified predictors of annual CBEs and
      mammograms. RESULTS: Among 859 YBCS (n = 340 Black; n = 519 White/Other; mean age
      = 51.0 +/- 5.9; diagnosed 11.0 +/- 4.0 years ago), the majority (> 85%) reported
      an annual CBE and a mammogram. Black YBCS in the study were more likely to report
      lower rates of annual mammography and more barriers accessing care compared to
      White/Other YBCS. Having a routine source of care, confidence to use healthcare
      services, perceived expectations from family members and healthcare providers to
      engage in cancer surveillance, and motivation to comply with these expectations
      were significant predictors of having annual CBEs and annual mammograms. Cost
      related lack of access to care was a significant barrier to annual mammograms.
      CONCLUSIONS: Routine source of post-treatment care facilitated breast cancer
      surveillance above national average rates. Persistent disparities regarding
      access to mammography surveillance were identified for Black YBCS, primarily due
      to lack of access to routine source of care and high out-of-pocket costs.
      IMPLICATIONS: Public health action targeting cancer surveillance in YBCS should
      ensure routine source of post-treatment care and address cost-related barriers.
      Clinical Trials Registration Number: NCT01612338.

PMID- 29353366
TI  - Is invasion a necessary step for metastases in breast cancer?
AB  - PURPOSE: To review the empirical evidence to support the conventional
      (sequential) model of breast cancer progression, which is based on the paradigm
      that cancer passes through several stages, including an in situ stage prior to an
      invasive stage, and thereafter (in some cases) disseminates to the lymph nodes
      and distant organs. METHODS: We review the cancer literature of the last 50 years
      which relates to the prevention of invasive breast cancer (through radiotherapy
      or surgery) and reductions in the mortality for breast cancer. RESULTS: For both
      invasive cancers and DCIS, the literature indicates that prevention of in-breast
      invasive recurrences does not prevent death from breast cancer. Moreover, the
      presence of residual cancer cells in the breast after breast-conserving surgery
      does not compromise the cure rate. CONCLUSION: We propose an alternate (parallel)
      model of breast cancer wherein there is a small pool of cancer stem cells which
      have metastatic potential from their inception and which disseminate
      synchronously through several routes-to the breast stroma, to the lymph nodes and
      to distant organs. Cancer cells which disseminate to the breast give rise to
      cells which make up the bulk of the tumour mass but these are not the source of
      the distant metastases.

PMID- 29353370
TI  - Sleep and circadian rhythms in health and disease: a complex interplay.

PMID- 29353369
TI  - Mental health professionals' attitudes towards mental illness: professional and
      cultural factors in the INTER NOS study.
AB  - BACKGROUND: Research shows that personnel working in mental health facilities may
      share some of the societal prejudices towards mental illness. This might result
      in stigmatizing behaviours towards people suffering from mental disorders,
      undermining the quality of their care. AIMS: To describe and compare attitudes
      towards mental illness across a sample of professionals working in a wide range
      of mental health facilities in Spain, Portugal and Italy. METHOD: We administered
      a survey to personnel including two questionnaires related to stigmatizing
      attitudes: The Community Attitudes toward the Mentally Ill (CAMI) and the
      Attribution Questionnaire (AQ-27). Data were compared according to professional
      category, work setting and country. RESULTS: 34.06% (1525) professionals of the
      surveyed population responded adequately. Psychologists and social therapists had
      the most positive attitudes, and nursing assistants the most negative, on most
      factors of CAMI and AQ-27. Community staff had more positive attitudes than
      hospital-based professionals in most factors on CAMI and in discriminatory
      responses on AQ-27. CONCLUSIONS: Globally, mental health professionals showed a
      positive attitude towards mental illness, but also a relative support to coercive
      treatments. There are differences in attitudes modulated by professional category
      and setting. Results can guide preventive strategies, particularly for the
      hospital-based and nursing staff.

PMID- 29353371
TI  - A Systematic Assessment of Google Search Queries and Readability of Online
      Gynecologic Oncology Patient Education Materials.
AB  - The Internet is a major source of health information for gynecologic cancer
      patients. In this study, we systematically explore common Google search terms
      related to gynecologic cancer and calculate readability of top resulting
      websites. We used Google AdWords Keyword Planner to generate a list of commonly
      searched keywords related to gynecologic oncology, which were sorted into five
      groups (cervical cancer, ovarian cancer, uterine cancer, vulvar cancer, vaginal
      cancer) using five patient education websites from sgo.org . Each keyword was
      Google searched to create a list of top websites. The Python programming language
      (version 3.5.1) was used to describe frequencies of keywords, top-level domains
      (TLDs), domains, and readability of top websites using four validated formulae.
      Of the estimated 1,846,950 monthly searches resulting in 62,227 websites, the
      most common was cancer.org . The most common TLD was *.com. Most websites were
      above the eighth-grade reading level recommended by the American Medical
      Association (AMA) and the National Institute of Health (NIH). The SMOG Index was
      the most reliable formula. The mean grade level readability for all sites using
      SMOG was 9.4 +/- 2.3, with 23.9% of sites falling at or below the eighth-grade
      reading level. The first ten results for each Google keyword were easiest to read
      with results beyond the first page of Google being consistently more difficult.
      Keywords related to gynecologic malignancies are Google-searched frequently. Most
      websites are difficult to read without a high school education. This knowledge
      may help gynecologic oncology providers adequately meet the needs of their
      patients.

PMID- 29353372
TI  - The variable position of the inferior alveolar nerve (IAN) in the mandibular
      ramus: a computed tomography (CT) study.
AB  - INTRODUCTION: This study was designed to quantify the important anatomical
      landmarks and the path of the inferior alveolar nerve (IAN) within the human
      mandibular body and ramus, in particular with reference to the bilateral sagittal
      split osteotomy (BSSO). MATERIALS AND METHODS: Four hundred and eleven CT scans
      were studied, 299 of these were involved in determining the position of lingula;
      and 230 were involved in determining the course of IAN in the mandibular molar
      region, namely from the mesial of the mandibular first molar to the distal of the
      mandibular second molar; 118 were involved with both measurements. RESULTS: On
      average, the lingula was located 17.0 +/- 2.2 mm from the external oblique ridge;
      11.6 +/- 2.0 mm from the internal oblique ridge; 17.2 +/- 2.7 mm from the sigmoid
      notch; and 15.6 +/- 1.9 mm from the posterior border of the mandible. The course
      of the IAN in the mandibular molar region was found to descend vertically from
      the distal of the mandibular second molar (7) to reach its lowest point between
      the first and second molars (6 and 7), and then ascend towards the mesial of the
      first molar (6). Horizontally, the IAN was found to traverse medially between the
      distal of the 7 and the middle of the 7, and then changes its path laterally
      towards the mesial of the 6. CONCLUSION: Precise knowledge of the individual's
      position of the IAN will help surgical planning.

PMID- 29353373
TI  - Disturbance of Metabotropic Glutamate Receptor-Mediated Long-Term Depression
      (mGlu-LTD) of Excitatory Synaptic Transmission in the Rat Hippocampus After
      Prenatal Immune Challenge.
AB  - Maternal immune challenge has proved to induce moderate to severe behavioral
      disabilities in the offspring. Cognitive/behavioral deficits are supported by
      changes in synaptic plasticity in different brain areas. We have reported
      previously that prenatal exposure to bacterial LPS could induce inhibition of
      hippocampal long-term potentiation (LTP) in the CA1 area of the juvenile/adult
      male offspring associated with spatial learning inabilities. Nevertheless,
      deficits in plasticity could be observed at earlier stages as shown by the early
      loss of long-term depression (LTD) in immature animals. Moreover, aberrant forms
      of plasticity were also evidenced such as the transient occurrence of LTP instead
      of LTD in 15-25 day-old animals. This switch from LTD to LTP seemed to involve
      the activation of metabotropic glutamate receptor subtype 1 and 5 (mGlu1/5). We
      have thus investigated here whether the long-term depression elicited by the
      direct activation of these receptors (mGlu-LTD) with a selective agonist was also
      disturbed after prenatal stress. We find that in prenatally stressed rats,
      mGlu1/5 stimulation elicits long-term potentiation (mGlu-LTP) independently of N
      methyl-D-aspartate receptors. Both mGlu5 and mGlu1 receptors are involved in this
      switch of plasticity. Moreover, this mGlu-LTP is still observed at later
      developmental stages than previously reported, i.e. after 25 day-old. In
      addition, increasing synaptic GABA with tiagabine tends to inhibit mGlu-LTP
      occurrence. By contrast, long-term depression induced with the activation of CB1
      cannabinoid receptor is unaffected by prenatal stress. Therefore, prenatal stress
      drastically alters mGlu1/5-associated plasticity throughout development. MGlu
      mediated plasticity is an interesting parameter to probe the long-lasting
      deficits reported in this model.

PMID- 29353374
TI  - BDNF Activates mTOR to Upregulate NR2B Expression in the Rostral Anterior
      Cingulate Cortex Required for Inflammatory Pain-Related Aversion in Rats.
AB  - The mechanistic target of rapamycin (mTOR) has been demonstrated to mediate pain
      related aversion induced by formalin in the rostral anterior cingulate cortex
      (rACC). However, it remains unclear the signaling pathways and regulatory
      proteins involved. In the rACC, brain-derived neurotrophic factor (BDNF), an
      activity-dependent neuromodulator, has been shown to play a role in the
      development and persistence of chronic pain. In this study, we used a rat
      formalin-induced inflammatory pain model to demonstrate BDNF up-regulation in the
      rACC. Stimulation with exogenous BDNF up-regulated mTOR, whilst cyclotraxin B
      (CTX-B), a tropomyosin receptor kinase B (TrkB) antagonist, down-regulated mTOR.
      Our results suggest BDNF could activate an mTOR signaling pathway. Subsequently,
      we used formalin-induced conditioned place avoidance (F-CPA) training in rat
      models to investigate if mTOR activation was required for pain-related aversion.
      We demonstrated that BDNF/mTOR signaling could activate the NMDA receptor subunit
      episilon-2 (NR2B), which is required for F-CPA. Our results reveal that BDNF
      activates mTOR to up-regulate NR2B expression, which is required for inflammatory
      pain-related aversion in the rACC of rats.

PMID- 29353375
TI  - Comparative Effects of Hydrogen Sulfide-Releasing Compounds on [3H]D-Aspartate
      Release from Bovine Isolated Retinae.
AB  - We investigated the pharmacological actions of a slow-releasing H2S donor, GYY
      4137; a substrate for the biosynthesis of H2S, L-cysteine and its precursor, N
      acetylcysteine on potassium (K+; 50 mM)-evoked [3H]D-aspartate release from
      bovine isolated retinae using the Superfusion Method. GYY 4137 (10 nM-10 uM), L
      cysteine (100 nM-10 uM) and N-acetylcysteine (10 uM-1 mM) elicited a
      concentration-dependent decrease in K+-evoked [3H]D-aspartate release from
      isolated bovine retinae without affecting basal tritium efflux. At equimolar
      concentration of 10 uM, the rank order of activity was as follows: L-cysteine >
      GYY 4137 > N-acetylcysteine. A dual inhibitor of the biosynthetic enzymes for
      H2S, cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), amino
      oxyacetic acid (AOA; 3 mM) reversed the inhibitory responses caused by GYY 4137,
      L-cysteine and N-acetylcysteine on K+-evoked [3H]D-aspartate release.
      Glibenclamide (300 uM), an inhibitor of KATP channels blocked the inhibitory
      action of GYY 4137 and L-cysteine but not that elicited by N-acetylcysteine on K+
      induced [3H]D-aspartate release. The inhibitory effect of GYY 4137 and L-cysteine
      on K+-evoked [3H]D-aspartate release was reversed by the non-specific inhibitor
      of nitric oxide synthase (NOS), L-NAME (300 uM). Furthermore, a specific
      inhibitor of inducible NOS (iNOS), aminoguanidine (10 uM) blocked the inhibitory
      action of L-cysteine on K+-evoked [3H]D-aspartate release. We conclude that both
      donors and substrates for H2S production can inhibit amino acid neurotransmission
      in bovine isolated retinae, an effect that is dependent, at least in part, upon
      the intramural biosynthesis of this gas, and on the activity of KATP channels and
      NO synthase.

PMID- 29353376
TI  - Injury Prevention in Baseball: from Youth to the Pros.
AB  - PURPOSE OF REVIEW: This review examines recent literature on injury epidemiology
      and prevention in the sport of baseball from youth to professional levels. RECENT
      FINDINGS: Overuse is the predominant mechanism of injury in youth baseball
      players. Newer stretching and exercise protocols may help prevent these injuries.
      At the professional level, however, overuse has not been proven to correlate with
      increased injury incidence, but pitch counts are still monitored. There continues
      to be a rise in operations performed for baseball-related injuries, including
      ulnar collateral ligament (UCL) reconstruction, particularly in younger athletes.
      As the level of play increases, there is significant loss of participation due to
      injuries, such as the UCL in the upper extremity and the hamstrings in the lower
      extremity. Baseball is a widely popular sport, which has led to a focus on injury
      epidemiology and prevention. While the majority of research regarding baseball
      injuries focuses on pitchers, fielders and catchers are also at risk. In an
      attempt to decrease non-contact injuries in the upper and lower extremities,
      stretching and strengthening exercises are vitally important. Because injury
      profiles demonstrate significant variability from youth to professional baseball,
      unique prevention strategies are likely necessary at each level. More research is
      needed to develop and validate appropriately targeted injury prevention programs.

PMID- 29353377
TI  - Highly synergistic activity of melittin with imipenem and colistin in biofilm
      inhibition against multidrug-resistant strong biofilm producer strains of
      Acinetobacter baumannii.
AB  - The rapid increase of drug resistance and failure of available antibiotics to
      treat biofilm-associated infections is of great health concern. Accordingly, our
      study aimed to evaluate the synergistic antibacterial, biofilm inhibitory, and
      biofilm removal activities of melittin in combination with colistin, imipenem,
      and ciprofloxacin against multidrug-resistant (MDR) strong biofilm producer
      Acinetobacter baumannii isolates. The kinetics of biofilm formation were
      evaluated for the isolates for 144 h. Minimum inhibitory concentrations (MICs),
      minimum bactericidal concentrations (MBCs), minimum biofilm inhibitory
      concentrations (MBICs), and biofilm removal activities for melittin and
      combinations with antibiotics were determined. Inhibition of biofilm-associated
      protein (bap) expression by melittin was evaluated with real-time polymerase
      chain reaction (PCR). Field emission scanning electron microscopy (FE-SEM) was
      used to visualize the effect of synergism on the inhibition of biofilm
      production. The geometric means of the fractional inhibitory concentration index
      (FICi) for melittin-colistin, melittin-imipenem, and melittin-ciprofloxacin
      combinations were calculated as 0.31, 0.24, and 0.94, respectively. Comparing the
      geometric means of the removal activity for melittin, colistin, imipenem, and
      combinations of them in both 6 and 24 h showed a significant difference between
      the groups (p-value < 0.05). Exposure to melittin induced a statistically
      significant downregulation of bap mRNA levels in all isolates at sub-MIC doses.
      Analysis of the FE-SEM results demonstrated that the synergism of melittin
      colistin at 0.125-0.25 MUg inhibited biofilm formation completely. In conclusion,
      our findings indicate that melittin possesses considerable potential for use in
      combination with colistin and imipenem to treat infections caused by MDR strong
      biofilm producer A. baumannii isolates.

PMID- 29353378
TI  - Secular trends in the appropriateness of empirical antibiotic treatment in
      patients with bacteremia: a comparison between three prospective cohorts.
AB  - The objective of this study was to explore whether the percentage of
      inappropriate empirical antibiotic treatment in patients with bacteremia changed
      over time and to understand the factors that brought on the change. Three
      prospective cohorts of patients with bacteremia in three different periods
      (January 1st, 1988 to December 31st, 1989; May 1st, 2004 to November 30, 2004;
      May 1st, 2010 to April 30, 2011) were compared. Analysis was performed on a total
      of 811 patients. In 2010-2011, 55.9% (76/136) of patients with bacteremia
      received inappropriate empirical treatment, compared with 34.5% (170/493) and
      33.5% (55/164) in the first and second periods, respectively, in a significant
      upward trend (p = 0.001). Resistance to antibiotics increased significantly
      during the study period. The following variables were included in the
      multivariate analysis assessing risk factors for inappropriate empirical
      treatment: study period (third period) [odds ratio, OR = 2.766 (95% confidence
      interval, CI, 1.655-4.625)], gender (male) [OR = 1.511 (1.014-2.253)], pathogen
      carrying extended-spectrum beta-lactamases [OR = 10.426 (4.688-23.187)],
      multidrug-resistant Acinetobacter baumannii [OR = 5.428 (2.181-13.513)], and
      skin/soft infections [OR = 3.23 (1.148-9.084)]. A model excluding microbiological
      data included: gender (male) [OR = 1.648 (1.216-2.234)], study period (third
      period) [OR = 2.446 (1.653-3.620)], hospital-acquired infection [OR = 1.551
      (1.060-2.270)], previous use of antibiotics [OR = 1.815 (1.247-2.642)], bedridden
      patient [OR = 2.019 (1.114-3.658)], and diabetes mellitus [OR = 1.620 (1.154
      2.274)]. We have observed a worrisome increase in the rate of inappropriate
      empirical treatment of bacteremia. We need tools that will allow us better
      prediction of the pathogen and its susceptibilities during the first hours of
      managing a patient suspected of a severe bacterial infection.

PMID- 29353379
TI  - Coagulase-negative staphylococci are associated to the mild inflammatory pattern
      of healthcare-associated meningitis: a retrospective study.
AB  - The epidemiology of healthcare-associated meningitis (HAM) is dominated by
      commensal bacteria from the skin, as coagulase-negative staphylococci (CoNS). We
      hypothesized that the pauci-symptomatic and mild inflammatory patterns of HAM are
      related to the low pathogenic state of CoNS. Our aim was to describe clinical and
      biological features of CoNS HAM, compared to other HAM. All consecutive patients
      with HAM admitted in our hospital were retrospectively included from 2007 to
      2014. HAM due to CoNS were compared to HAM caused by other bacteria (controls)
      for clinical and laboratory patterns. Seventy-one cases of HAM were included,
      comprising 18 CoNS and 53 controls. Patients were not different in terms of
      baseline characteristics. CoNS HAM occurred later after the last surgery than
      controls (17 vs. 12 days, p = 0.029) and had higher Glasgow Coma Scale (GCS)
      score (14 vs. 13, p = 0.038). Cerebrospinal fluid (CSF) analysis revealed a lower
      pleocytosis (25 vs. 1340/mm3, p < 0.001), a higher glucose level (3.75 vs. 0.8
      mmol/L, p < 0.001), and a lower protein level (744 vs. 1751 mg/L, p < 0.001) in
      the CoNS group than in the control group, respectively. HAM due to CoNS was
      significantly less symptomatic and less inflammatory than HAM due to other
      bacteria.

PMID- 29353380
TI  - Crystal structure of the NADP+ and tartrate-bound complex of L-serine 3
      dehydrogenase from the hyperthermophilic archaeon Pyrobaculum calidifontis.
AB  - A gene encoding L-serine dehydrogenase (L-SerDH) that exhibits extremely low
      sequence identity to the Agrobacterium tumefaciens L-SerDH was identified in the
      hyperthermophilic archaeon Pyrobaculum calidifontis. The predicted amino acid
      sequence showed 36% identity with that of Pseudomonas aeruginosa L-SerDH,
      suggesting that P. calidifontis L-SerDH is a novel type of L-SerDH, like Ps.
      aeruginosa L-SerDH. The overexpressed enzyme appears to be the most thermostable
      L-SerDH described to date, and no loss of activity was observed by incubation for
      30 min at temperatures up to 100  degrees C. The enzyme showed substantial
      reactivity towards D-serine, in addition to L-serine. Two different crystal
      structures of P. calidifontis L-SerDH were determined using the Se-MAD and MR
      method: the structure in complex with NADP+/sulfate ion at 1.18 A and the
      structure in complex with NADP+/L-tartrate (substrate analog) at 1.57 A. The fold
      of the catalytic domain showed similarity with that of Ps. aeruginosa L-SerDH.
      However, the active site structure significantly differed between the two
      enzymes. Based on the structure of the tartrate, L- and D-serine and 3
      hydroxypropionate molecules were modeled into the active site and the substrate
      binding modes were estimated. A structural comparison suggests that the wide
      cavity at the substrate binding site is likely responsible for the high
      reactivity of the enzyme toward both L- and D-serine enantiomers. This is the
      first description of the structure of the novel type of L-SerDH with bound NADP+
      and substrate analog, and it provides new insight into the substrate binding
      mechanism of L-SerDH. The results obtained here may be very informative for the
      creation of L- or D-serine-specific SerDH by protein engineering.

PMID- 29353381
TI  - Effect of Kaempferol Pretreatment on Myocardial Injury in Rats.
AB  - The present study was undertaken to evaluate the effect of kaempferol in
      isoprenaline (ISP)-induced myocardial injury in rats. ISP was administered
      subcutaneously for two subsequent days to induce myocardial injury. Assessment of
      myocardial injury was done by estimation of hemodynamic functions, myocardial
      infarcted area, cardiac injury markers, lipid profile, oxidative stress, pro
      inflammatory cytokines and histopathology of heart and liver. Rats pretreated
      with kaempferol showed reduction in the myocardial infarcted area and heart rate.
      However, no improvement was observed in change in body weight, mean arterial,
      systolic and diastolic blood pressure. Kaempferol showed significant decrease in
      serum LDH, CK-MB, troponin-I and lipid profile. However, highest dose of
      kaempferol did not reduce the serum triglyceride level. Further, antioxidant
      enzymes, SOD and catalase, were also higher. However, reduced glutathione, serum
      SGOT and creatinine did not show any improvement. Kaempferol showed reduction in
      MDA level. Kaempferol at highest dose showed reduction in pro-MMP-2 expression
      and MMP-9 level. mRNA expression level of TNF-alpha was not different in
      kaempferol-pretreated myocardial injured rats with ISP-alone group. Pretreatment
      with kaempferol at highest dose showed mild mononuclear infiltration and
      degenerative changes in heart tissue section of myocardial injured rats. Rats
      pretreated with kaempferol at higher concentration showed normal cordlike
      arrangement of hepatocytes with moderate swelling of hepatocytes (vacuolar
      degeneration) around the central vein. Study suggests that kaempferol attenuated
      lipid profile, infarcted area and oxidative stress in ISP-induced myocardial
      injury in rats.

PMID- 29353382
TI  - A Closer Look at Transcendence and Its Relationship to Mental Health.
AB  - Experiences of transcendence can promote growth, creativity and altruism, but
      often exist in tension with critical thought and can feature problematically in
      certain mental disorders. Identification of the core elements in the experience
      of transcendence-suspending disbelief, being moved or inspired, surrendering
      oneself and identifying within a larger context, can clarify its relationship to
      psychopathology, and the basis for a clinician's role. To help individuals engage
      transcendent resources well, clinicians can help patients recognize how
      depression and trauma may interfere with engagement, masochistic and magical
      tendencies may distort healthy self-surrender, and vulnerability to social
      pressure may interfere with mature identification with a larger context or
      community.

PMID- 29353383
TI  - Religion and Well-Being: The Mediating Role of Positive Virtues.
AB  - Researchers have consistently advocated positive associations between religion
      and well-being. The present research takes a step forward and explores potential
      mechanisms behind the same. The mediating role of a surprisingly neglected
      mechanism, positive virtues, specifically gratitude, forgiveness and altruism, is
      studied through a quantitative study on a sample of 220 adult respondents
      residing in Delhi NCR. The participants adhered to one of the six major religions
      present in India. Mediational analysis revealed that gratitude mediated the
      relationship between religiosity, spirituality and well-being via two pathways of
      forgiveness and altruism. The implications for researchers and practitioners
      working in the field of mental health are discussed.

PMID- 29353384
TI  - The Effect of Self-Care Education on Emotional Intelligence of Iranian Nursing
      Students: A Quasi-experimental Study.
AB  - This study aimed to determine the effect of self-care training on emotional
      intelligence of nursing students. This quasi-experimental study was conducted on
      nursing students of Mazandaran University of Medical Sciences in 2016. The
      subjects (60 students) that were collected with random sampling method were
      divided into experimental and control groups, and then, self-care behaviors were
      taught to the experimental group' students in 12 sessions by using a checklist.
      The subjects of control group were not taught. Emotional intelligence was
      measured by using Bradberry and Greaves' standard questionnaire before and after
      the intervention. Emotional intelligence scores of students in the experimental
      group showed positive and significant change between before (75.33 +/- 7.23) and
      after (125.70 +/- 7.79) of training (P < 0.001). Also t test shows a significant
      change in control (78.73 +/- 6.54) and experimental groups (125.70 +/- 7.79),
      after of training (P < 0.001). It is recommended that special programs be
      organized in order to improve the emotional intelligence of students that improve
      the likelihood of their success in life.

PMID- 29353385
TI  - The Relative Importance of Clinical, Economic, Patient Values and Feasibility
      Criteria in Cancer Drug Reimbursement in Canada: A Revealed Preferences Analysis
      of Recommendations of the Pan-Canadian Oncology Drug Review 2011-2017.
AB  - BACKGROUND: Most Canadian provinces and territories rely on the pan-Canadian
      Oncology Drug Review (pCODR) to provide recommendations regarding public
      reimbursement of cancer drugs. The pCODR review process considers four dimensions
      of value-clinical benefit, economic evaluation, patient-based values and adoption
      feasibility-but they do not define weights for individual decision criteria or an
      acceptable threshold for any of the criteria. Given this implicit review process,
      it is of interest to understand which factors appear to carry the most weight in
      pCODR recommendations using a revealed preferences approach. METHODS: Using
      publicly available decision summaries (n = 91) describing submissions and
      resulting recommendations 2011-2017, we extracted ten attributes that
      characterized each submission. Using logistic regression, we identified
      statistically significant attributes and estimated their relative impact in final
      recommendations. RESULTS: Clinical aspects appear to carry the greatest weight in
      the decision to reject or not reject, along with aspects of patient value
      (treatments with no alternatives were less likely to be rejected). Cost
      effectiveness does not appear to play a role in the initial decision to reject or
      not reject but is critical in full versus conditional approvals. There is
      evidence of a maximum acceptable threshold of around $Can140,000 per quality
      adjusted life-year (QALY) gained. CONCLUSION: A set of factors driving pCODR
      recommendations is identifiable, supporting the consistency of the review
      process. However, the implicit nature of the review process and the difficulty of
      extracting and interpreting some of the attribute levels used in the analysis
      suggests that the process may still lack full transparency.

PMID- 29353386
TI  - Population-based dose-response analysis of liver transcriptional response to
      trichloroethylene in mouse.
AB  - Studies of gene expression are common in toxicology and provide important clues
      to mechanistic understanding of adverse effects of chemicals. Most prior studies
      have been performed in a single strain or cell line; however, gene expression is
      heavily influenced by the genetic background, and these genotype-expression
      differences may be key drivers of inter-individual variation in response to
      chemical toxicity. In this study, we hypothesized that the genetically diverse
      Collaborative Cross mouse population can be used to gain insight and suggest
      mechanistic hypotheses for the dose- and genetic background-dependent effects of
      chemical exposure. This hypothesis was tested using a model liver toxicant
      trichloroethylene (TCE). Liver transcriptional responses to TCE exposure were
      evaluated 24 h after dosing. Transcriptomic dose-responses were examined for both
      TCE and its major oxidative metabolite trichloroacetic acid (TCA). As expected,
      peroxisome- and fatty acid metabolism-related pathways were among the most dose
      responsive enriched pathways in all strains. However, nearly half of the TCE
      induced liver transcriptional perturbation was strain-dependent, with abundant
      evidence of strain/dose interaction, including in the peroxisomal signaling
      associated pathways. These effects were highly concordant between the
      administered TCE dose and liver levels of TCA. Dose-response analysis of gene
      expression at the pathway level yielded points of departure similar to those
      derived from the traditional toxicology studies for both non-cancer and cancer
      effects. Mapping of expression-genotype-dose relationships revealed some
      significant associations; however, the effects of TCE on gene expression in liver
      appear to be highly polygenic traits that are challenging to positionally map.
      This study highlights the usefulness of mouse population-based studies in
      assessing inter-individual variation in toxicological responses, but cautions
      that genetic mapping may be challenging because of the complexity in gene
      exposure-dose relationships.

PMID- 29353389
TI  - The Design of a Pulse Oximeter to MIDI Output Conversion Unit - a Technical
      Report.

PMID- 29353388
TI  - Outcomes and cost-effectiveness of ultrasound-guided injection of the
      trochanteric bursa.
AB  - We hypothesized that ultrasound (US) guidance improves outcomes of corticosteroid
      injection of trochanteric bursitis. 40 patients with greater trochanteric pain
      syndrome defined by pain to palpation over the trochanteric bursa were randomized
      to injection with 5 ml of 1% lidocaine and 80 mg of methylprednisolone using (1)
      conventional anatomic landmark palpation guidance or (2) US guidance. Procedural
      pain (Visual Analogue Pain Scale), pain at outcome (2 weeks and 6 months),
      therapeutic duration, time-to-next intervention, and costs were determined. There
      were no complications in either group. Ultrasonography demonstrated that at least
      a 2-in (50.8 mm) needle was required to consistently reach the trochanteric
      bursa. Pain scores were similar at 2 weeks: US: 1.3 +/- 1.9 cm; landmark: 2.2 +/-
      2.5 cm, 95% CI of difference: - 0.7 < 0.9 < 2.5, p = 0.14. At 6 months, US was
      superior: US: 3.9 +/- 2.0 cm; landmark: 5.5 +/- 2.6 cm, 95% CI of difference: 0.8
      < 1.6 < 2.4, p = 0.036. However, therapeutic duration (US 4.7 +/- 1.4 months;
      landmark 4.1 +/- 2.9 months, 95% CI of difference - 2.2 < - 0.6 < 1.0, p = 0.48),
      and time-to-next intervention (US 8.7 +/- 2.9 months; landmark 8.3 +/- 3.8
      months, 95% CI of difference - 2.8 < - 0.4 < 2.0, p = 0.62) were similar.
      Costs/patient/year was 43% greater with US (US $297 +/- 99, landmark $207 +/- 95;
      p = 0.017). US-guided and anatomic landmark injection of the trochanteric bursa
      have similar 2-week and 6-month outcomes; however, US guidance is considerably
      more expensive and less cost-effective. Anatomic landmark-guided injection
      remains the method of choice, but should be routinely performed using a
      sufficiently long needle [at least a 2 in (50.8 mm)]. US guidance should be
      reserved for extreme obesity or injection failure.

PMID- 29353387
TI  - Inter-individual variation in health and disease associated with pulmonary
      infectious agents.
AB  - Respiratory infectious diseases resulting from bacterial or viral pathogens such
      as Mycobacterium tuberculosis, Streptococcus pneumoniae, respiratory syncytial
      virus (RSV), or influenza, are major global public health concerns. Lower
      respiratory tract infections are leading causes of morbidity and mortality, only
      behind ischemic heart disease and stroke (GBD 2015 LRI Collaborators in Lancet
      Infect Dis 17(11):1133-1161, 2017). Developing countries are particularly
      impacted by these diseases. However, while many are infected with viruses such as
      RSV (> 90% of all individuals are infected by age 2), only sub-populations
      develop severe disease. Many factors may contribute to the inter-individual
      variation in response to respiratory infections, including gender, age,
      socioeconomic status, nutrition, and genetic background. Association studies with
      functional single nucleotide polymorphisms in biologically plausible gene
      candidates have been performed in human populations to provide insight to the
      molecular genetic contribution to pulmonary infections and disease severity. In
      vitro cell models and genome-wide association studies in animal models of genetic
      susceptibility to respiratory infections have also identified novel candidate
      susceptibility genes, some of which have also been found to contribute to disease
      susceptibility in human populations. Genetic background may also contribute to
      differential efficacy of vaccines against respiratory infections. Development of
      new genetic mouse models such as the collaborative cross and diversity outbred
      mice should provide additional insight to the mechanisms of genetic
      susceptibility to respiratory infections. Continued investigation of
      susceptibility factors should provide insight to novel strategies to prevent and
      treat disease that contributes to global morbidity and mortality attributed to
      respiratory infections.

PMID- 29353390
TI  - Image-based Analysis of Emotional Facial Expressions in Full Face Transplants.
AB  - In this study, it is aimed to determine the degree of the development in
      emotional expression of full face transplant patients from photographs. Hence, a
      rehabilitation process can be planned according to the determination of degrees
      as a later work. As envisaged, in full face transplant cases, the determination
      of expressions can be confused or cannot be achieved as the healthy control
      group. In order to perform image-based analysis, a control group consist of 9
      healthy males and 2 full-face transplant patients participated in the study.
      Appearance-based Gabor Wavelet Transform (GWT) and Local Binary Pattern (LBP)
      methods are adopted for recognizing neutral and 6 emotional expressions which
      consist of angry, scared, happy, hate, confused and sad. Feature extraction was
      carried out by using both methods and combination of these methods serially. In
      the performed expressions, the extracted features of the most distinct zones in
      the facial area where the eye and mouth region, have been used to classify the
      emotions. Also, the combination of these region features has been used to improve
      classifier performance. Control subjects and transplant patients' ability to
      perform emotional expressions have been determined with K-nearest neighbor (KNN)
      classifier with region-specific and method-specific decision stages. The results
      have been compared with healthy group. It has been observed that transplant
      patients don't reflect some emotional expressions. Also, there were confusions
      among expressions.

PMID- 29353391
TI  - Detection of sleep-disordered breathing with ambulatory Holter monitoring.
AB  - PURPOSE: Obstructive sleep apnea (OSA) syndrome is a common condition that can
      impact clinical outcomes among patients with cardiovascular disease. Screening
      all subjects with heart disease via polysomnography (PSG) is costly and resource
      limited. We sought to compare a Holter monitor-based algorithm to detect OSA to
      in-laboratory polysomnography (PSG). METHODS: Prospective cohort study of
      patients undergoing in-laboratory attended PSG for the evaluation of OSA. A
      standard 12-lead Holter monitor was attached to patients at the initiation of
      PSG. Holter-derived respiratory disturbance index (HDRDI) was extracted from the
      respiratory myogram, based on detecting skeletal muscle "noise" detected on the
      baseline. Apneic and hypopneic episodes were identified by comparing sudden
      changes in the myogram to abrupt increases in heart rate. The HDRDI was compared
      with the PSG-derived apnea-hypopnea index (PDAHI). RESULTS: Thirty patients
      underwent simultaneous Holter monitoring and overnight diagnostic PSG. An ROC
      curve for peak HDRDI was 0.79 (95% CI 0.61, 0.97) for OSA, with sensitivity of
      94.4% and specificity of 54.5%. A cutoff value of HDRDI < 10 appeared to identify
      those individuals without clinically significant sleep-disordered breathing.
      CONCLUSION: Holter-derived respiration detected OSA comparable to PSG. Further
      study is warranted to determine its utility for screening and diagnosing OSA in
      appropriately selected patients.

PMID- 29353392
TI  - A preliminary survey on prevalence and knowledge about different aspects of
      somnambulism in Buner District of Khyber Pakhtunkhwa, Pakistan.
AB  - PURPOSE: Present study was aimed to investigate the prevalence and knowledge
      about different aspects of somnambulism in general population of Buner District,
      KP, Pakistan, during December 2015-November 2016. METHODS: Data was collected
      through convenient sampling technique which was comprised of structured and
      detailed questionnaire. Collected data regarding different actions performed by
      sleepwalkers were adjusted through a weighted variable to generalize results.
      Univariate and multivariate logistic regression was used to evaluate association
      between variables related to somnambulism. Their odds ratios (ORs) were reported
      with their corresponding 95% CIs. RESULTS: In total, 11,881 individuals were
      surveyed, of which 448 (4%) suffered with sleep disorder. Females 256/448 (57%)
      were more prevalent as compared to males 192/448 (43%). Prevalence of
      somnambulism among children was 38% whereas 94% sufferers reported no effect on
      their growth. Majority of respondents reported that main cause of sleepwalking is
      stress and tension. Somnambulism was taken normal and mostly amusing disorder by
      sufferers and their families. CONCLUSION: Sleepwalking is not age specific and
      serious disorder. Sleepwalkers need special care during their episode due to
      unconsciousness.

PMID- 29353393
TI  - 131I-Induced Graves' disease in patients treated for toxic multinodular goitre:
      systematic review and descriptive analysis.
AB  - BACKGROUND: Graves' disease (GD) arising after the treatment of toxic
      multinodular goitre (TMNG) with radioiodine has long been described but it
      remained unclear whether GD was in fact iodine induced, its incidence, risk
      factors, natural history and treatment outcomes. METHODS: A systematic search
      using The Cochrane Library, Medline and PubMed Central allowed the pooling of
      data from 3633 patients with thyroid autonomy, 1340 patients with TMNG, to fill
      gaps in knowledge, regarding the clinical expression of iodine-induced GD (131I
      IGD) in adults. RESULTS: 131I-IGD developed in 0-5.3% of those with thyroid
      autonomy (first year) and in 5-5.4% of those with TMNG, 3-6 months after
      treatment. Patients with toxic adenoma were less affected. 131I-IGD was more
      common in patients with pre-treatment direct or indirect signs of autoimmunity:
      positive anti-TPO (p < 0.05), glandular hypoechogenicity, TRAbs within reference
      range, diffuse uptake on 99mTc-pertechnetate scans (p < 0.05), findings that may
      increase the risk tenfold. 131I-IGD manifested 3 months after 131I, justifying
      15.4-29% of cases of relapse. The rate of spontaneous remission was 17-20% (6
      months) and the rate of relapse after a second 131I treatment 22-25%. The use of
      an uptake-based administered 131I activity led to a greater proportion of
      euthyroid patients (78% compared to 25-50% with the mass-based approach).
      CONCLUSIONS: GD may be triggered by 131I. The incidence of the condition is low.
      Several risk factors were consistently identified; some have shown to raise the
      risk significantly. 131I-IGD seems more treatment resistant than iodine
      independent GD and the best resolution rates were achieved with uptake-based
      selected iodine activities.

PMID- 29353394
TI  - Comparison of the effects of the L-dopa and insulin tolerance tests on cortisol
      secretion.
AB  - PURPOSE: The aims of the present study are to evaluate the effect of L-dopa on
      the secretion of cortisol and adrenocorticotropic hormone (ACTH) in short
      children and compare the performance of this test with the insulin tolerance test
      (ITT) in a large number of patients. METHODS: A total of 29 short but otherwise
      healthy children [mean age 9.5 +/- 3.1 years (range 3.7-14.9 years)] who had
      inadequate growth hormone (GH) responses to ITT, which was performed as the first
      test, were consecutively enrolled in this study. GH, cortisol, and ACTH levels
      were measured just before administration of L-dopa and then at 30-min intervals
      afterward over a total time of 120 min. Peak concentrations of cortisol and ACTH
      exceeding 18 ug/dL (496 mmol/L) and 46 pg/mL (10.2 pmol/L), respectively, were
      defined as an adequate response. RESULTS: While the L-dopa test revealed that 26
      of the 29 children (89.7%) had peak serum cortisol levels of > 18 ug/dL, the ITT
      revealed that only 23 children (79.3%) had adequate cortisol responses. The L
      dopa test revealed normal ACTH responses (> 46 pg/mL) in 24 (82.8%) patients.
      Peak cortisol levels were higher in children with normal ACTH responses than in
      those with subnormal ACTH responses (25.6 +/- 6.2 vs. 19.5 +/- 6.4 ug/dL, p =
      0.054), but the difference observed was statistically insignificant. CONCLUSION:
      The results of the current study confirm that the L-dopa test is a reliable test
      of cortisol secretion. As such, this test may be applicable to assessments of the
      hypothalamic-pituitary-adrenal axis.

PMID- 29353395
TI  - Comparison of osteoporosis in US adults with type 1 and type 2 diabetes mellitus.
AB  - PURPOSE: We examined bone mineral density (BMD) and osteoporosis prevalence in
      those with type 1 compared to type 2 diabetes derived from a nationally
      representative sample from the civilian community in the United States. METHODS:
      Data from the National Health and Nutrition Examination Survey (NHANES) for 2005
      2006, 2007-2008, 2009-2010, and 2013-2014 were merged to obtain a large sample of
      diabetics at least 20 years of age with participation in the interview and
      medical examination. Osteoporosis status was defined by BMD at the total femur,
      femoral neck, or total lumbar spine. Self-reported diabetics that were prescribed
      insulin within the first year of diagnosis, are currently taking insulin, and
      reported no prescriptions for any diabetic pills were classified as type 1.
      Remaining self-reported diabetics were deemed as having type 2. RESULTS: A total
      of 2050 diabetics were included in which 87 (4%) were classified as type 1. Type
      1 diabetics were found to have a significantly lower BMD at the total femur and
      femoral neck, but not at the lumbar spine in the adjusted models. Diabetics with
      type 1 were 4.7 times more likely to have osteoporosis than those with type 2.
      There was no significant relationship between diabetes type and BMD or
      osteoporosis prior to adjustment for confounders. CONCLUSIONS: Although our
      results show an increased likelihood of osteoporosis among those with type 1
      diabetes, future studies including a larger sample from a community population
      are needed. It may benefit diabetics, especially those with type 1, to initiate
      osteoporosis screening methods including evaluation of fracture risk, bone
      quality, and BMD measurements at multiple sites earlier than recommended.

PMID- 29353396
TI  - The differences in the assessments of side effects at an oncology outpatient
      clinic.
AB  - Background There is a growing interest in the use of targeted and immunotherapies
      in oncology. However, the assessment of side effects can be different due to
      interpretation of patients' health status by healthcare professionals in oncology
      outpatient clinics. Objective To demonstrate the differences in the assessments
      of side effects conducted independently by a clinical pharmacist and nurses in
      patients who receive targeted therapies at an oncology outpatient clinic. Setting
      The study was conducted at the University Oncology Hospital in an outpatient
      clinic from October 2015 to March 2016. Method Patients receiving ipilimumab,
      nivolumab, pembrolizumab, bevacizumab, panitumumab or cetuximab during study
      period were included. The assessment of side effects was conducted by a
      pharmacist and nurse independently using the NCI-CTCAE version-2. Main outcome
      measure To compare the severity assessments of side effects between a clinical
      pharmacist and nurses in an outpatient clinic. Results During the study, 204
      visits for 43 patients with a total of 5508 side effect assessments were recorded
      where 1137 (20.64%) assessments were graded differently. Out of 1137 assessments,
      473 of them were graded higher by a clinical pharmacist whereas 664 were graded
      higher by nurses. Statistically significant differences were detected in the
      assessment of vomiting, taste changes, sense changes, alopecia, fatigue, mood
      changes, anxiety, hearing impairment, and allergic reactions. Conclusion An
      assessment of side effects by healthcare providers in patients with cancer may be
      challenging due to an increased workload in clinics and undistinguishable
      symptoms of side effects and cancer itself. Therefore, a new care model which
      increases an interprofessional communication may improve pharmaceutical care in
      oncology outpatient clinics.

PMID- 29353397
TI  - Patients' perceptions of pharmacist-managed diabetes services in the ambulatory
      care and community settings within Singapore.
AB  - Background Qualitative evidence on patients' perceptions of pharmacist-managed
      diabetes services (PMDSs) is limited. Objective To explore patients' perceptions
      of PMDSs Setting Patients being cared for in the outpatient settings in
      Singapore. Methods This focus group included patients who were diagnosed with
      type 2 diabetes, spoke either English or Mandarin, attended PMDSs for at least 6
      months in the ambulatory care or community settings, and were at least 21 years
      of age. Patients with cognitive impairments or mobility issues were excluded.
      Thematic analysis of transcribed audio recordings was undertaken. Main outcomes
      measure Patients' care experiences with PMDSs. Results A total of 26 patients
      from two outpatient ambulatory care clinics and three retail pharmacies were
      assembled into four focus groups based on the care setting. Four themes
      abstracted from focus group data illustrated patients' perspectives on PMDSs in
      fulfilling their health needs, delivery and quality of service, changes
      attributed to the service, and suggestions for improvement of service. The
      patients highlighted that PMDSs fulfilled their need for information on diabetes.
      They also felt comfortable speaking to the pharmacists about their health, and
      they appreciated the role of the pharmacists as healthcare professionals.
      Furthermore, the patients reported better diabetes-related self-empowerment via
      increased medication knowledge and lifestyle modification. Some of the patients
      noted that medication adherence and glycemic control had improved. Suggestions to
      improve PMDSs were minimal. Conclusions Overall, patients with type 2 diabetes
      had positive perceptions of PMDSs regardless of the care settings.

PMID- 29353398
TI  - New Strategies of ARV: the Road to Simplification.
AB  - PURPOSE OF REVIEW: Simplification of antiretroviral therapy is a strategy aiming
      to reduce pill burden, drug interactions, and toxicity. This review focuses on
      the most recent and important studies evaluating a reduction on the number of
      drugs for HIV treatment, both in naive and virologically suppressed patients.
      RECENT FINDINGS: Interesting studies have been performed in the past years
      testing dual therapy and monotherapy, with variable rates of virological control.
      Novel therapeutics like immunotherapy or long-acting antiretrovirals can also be
      considered for simplification. Reducing the number of drugs for HIV treatment can
      be an option for selected patients. Current available evidence favors dual
      therapy over monotherapy. Future research should seek to identify the best
      candidates for simplification.

PMID- 29353399
TI  - MRI findings in glutamic acid decarboxylase associated autoimmune epilepsy.
AB  - PURPOSE: Glutamic acid decarboxylase (GAD65) has been implicated in a number of
      autoimmune-associated neurologic syndromes, including autoimmune epilepsy. This
      study categorizes the spectrum of MRI findings in patients with a clinical
      diagnosis of autoimmune epilepsy and elevated serum GAD65 autoantibodies.
      METHODS: An institutional database search identified patients with elevated serum
      GAD65 antibodies and a clinical diagnosis of autoimmune epilepsy who had
      undergone brain MRI. Imaging studies were reviewed by three board-certified
      neuroradiologists and one neuroradiology fellow. Studies were evaluated for
      cortical/subcortical and hippocampal signal abnormality, cerebellar and cerebral
      volume loss, mesial temporal sclerosis, and parenchymal/leptomeningeal
      enhancement. The electronic medical record was reviewed for relevant clinical
      information and laboratory markers. RESULTS: A study cohort of 19 patients was
      identified. The majority of patients were female (84%), with a mean age of onset
      of 27 years. Serum GAD65 titers ranged from 33 to 4415 nmol/L (normal < 0.02
      nmol/L). The most common presentation was medically intractable, complex partial
      seizures with temporal lobe onset. Parenchymal atrophy was the most common
      imaging finding (47%), with a subset of patients demonstrating
      cortical/subcortical parenchymal T2 hyperintensity (37%) or abnormal hippocampal
      signal (26%). No patients demonstrated abnormal parenchymal/leptomeningeal
      enhancement. CONCLUSION: The most common MRI finding in GAD65-associated
      autoimmune epilepsy is disproportionate parenchymal atrophy for age, often
      associated with abnormal cortical/subcortical T2 hyperintensities. Hippocampal
      abnormalities are seen in a minority of patients. This constellation of findings
      in a patient with medically intractable epilepsy should raise the possibility of
      GAD65 autoimmunity.

PMID- 29353400
TI  - A STARD-compliant prediction model for diagnosing thrombotic microangiopathies.
AB  - Aim of the study was the definition of a predictive model for the initial
      diagnosis of thrombotic microangiopathies (TMA). We retrospectively collected
      data on all adult patients admitted to the Gemelli Hospital from 2010 to 2014.
      ICD-9 codes from primary diagnoses were used for TMA diagnosis. Demographic and
      laboratory characteristics on admission of patients with TMA were then compared
      with a random sample of 500 patients with other diagnoses. The prediction model
      was externally validated in a cohort from another hospital. Overall, 23 of
      187,183 patients admitted during the study period received a primary diagnosis of
      TMA. LDH (OR 1.26, 95% CI 1.05, 1.63) and platelets (OR 0.96, 95% CI 0.94, 0.98)
      were the only independent predictors of TMA. The AUROC of the final model
      including only LDH and platelets was 0.96 (95% CI 0.91, 1.00). The Hosmer
      Lemeshow (HL) test (p = 0.54) suggested good calibration. Our model also
      confirmed good discriminatory power (AUROC 0.72 95% CI 0.60, 0.84) and
      calibration (HL test p = 0.52) in the validation sample. We present a simple
      prediction model for use in diagnosing TMA in hospitalized patients. The model
      performs well and can help clinicians to identify patients at high risk of TMA.

PMID- 29353401
TI  - Temporal Analysis of Factors Associated with EAT-10 in Outpatients with
      Oropharyngeal Dysphagia from a Tertiary Care Clinic.
AB  - Self-perception of disease is increasingly recognized as a determinant of health.
      The Eating Assessment Tool-10 (EAT-10) is a functional health status
      questionnaire that measures the symptomatic severity of dysphagia from the
      patient's perspective. The objective of this work was to identify factors
      (demographics, clinical variables, swallowing physiology, health-related quality
      of life) associated with longitudinal change in EAT-10 scores in outpatients with
      oropharyngeal dysphagia at a multi-disciplinary, tertiary care clinic. All
      patients with swallowing concerns that were included in the UW Madison Voice and
      Swallowing Outcomes database from 12/2012 to 04/2015 were invited to complete EAT
      10 and a general health-related quality of life survey (SF-12v2) at their initial
      evaluation and six months later. Forty-two patients were included in analysis (n
      = 42). Weaning from a gastrostomy tube was significantly associated with EAT-10
      improvement. Approximately 70% of the sample had mild dysphagia, and floor
      effects were observed for all EAT-10 items in this sample subset. Mean SF-12v2
      Physical Component Summary score was substantially lower than that of the general
      population. Significant, weak-moderate correlations were found between EAT-10 and
      SF-12v2 scores for all comparisons except for Physical Health Composite at six
      months (rs = = 0.24 to - 0.43). Weaning from a feeding tube appears to
      meaningfully improve self-perceived symptoms of dysphagia. Given the floor
      effects observed, validity of EAT-10 for patients with mild dysphagia should be
      examined. Future research should address contributors to self-perceived symptom
      change across the range of dysphagia severity.

PMID- 29353402
TI  - Factors Affecting the Referral Rate of the Hoarding Disorder at Primary Mental
      Health Care in Quebec.
AB  - Hoarding disorder (HD) places an important burden on people with HD, on their
      family members and society. In this paper we evaluate help-seeking in HD at
      primary mental health, measured in referral rate, together with its individual,
      environmental and structural correlates. We conducted an aggregate study by
      combining existing official data with our own survey data at the catchment area
      level. We found a mean annual referral rate of 1.58 (SD = 1.79) cases of HD in
      primary mental health facilities per 10,000 of adult population. The referrals
      rate correlated with socio-demographic characteristics of the catchment area, the
      availability of tools for clinical management of HD, and affiliation to a
      University Medical school. We also found that: (1) family members, neighbours,
      municipal workers and health professionals are the primary source of complaints
      for HD; (2) 72% of primary mental health facilities worked with HD in crisis
      situations, 52% expressed difficulties in obtaining the consent of people with HD
      for an intervention (3) health/social services professionals lack HD clinical
      management tools, training and formal collaboration with municipal (housing,
      building security, fire prevention) specialists. Improvement of the readiness of
      the health-system to deal with HD will improve help-seeking for formal medical
      counselling on the part of people with HD. We can improve this readiness by
      providing primary mental-health facilities with training, clinical management
      tools and by helping them to establish formal collaboration with municipalities
      and community organisations. University medical schools can take a leadership
      role and become centers catalysing the change in HD clinical management.

PMID- 29353403
TI  - Genetic polymorphism in Hsp90AA1 gene is associated with the thermotolerance in
      Chinese Holstein cows.
AB  - The heat shock protein 90 (Hsp90) is a copious and ubiquitous molecular chaperone
      which plays an essential role in many cellular biological processes. The
      objective of this study was to identify single nucleotide polymorphisms (SNPs) in
      the Hsp90AA1 gene and to determine their association with heat stress traits in
      Chinese Holstein cattle breed. Direct sequencing was used to identify new SNPs.
      Luciferase reporter assay methods were used to assess g.- 87G > C and g.4172A > G
      loci in the promoter activity and 3'-UTR, respectively. Quantitative real-time
      PCR was utilized to quantify the gene expression profile. Five SNPs were
      identified in 130 multiparous lactating cows: one SNP in the promoter, three SNPs
      in the coding region, and one in 3'-UTR were novel and reported for the first
      time in this study. As a result of promoter assay using dual luciferase assay
      system, the genotype CC showed the highest transcription activity region (13.67
      +/- 0.578) compared to the wild-type GG (3.24 +/- 0.103). On the other hand, the
      result revealed that one of the selected microRNAs (dme-miR-2279-5p) was found to
      interact with the Hsp90AA1 3'-UTR sequence and to suppress the reporter activity
      markedly in the presence of the allele G (2.480 +/- 0.136). The expression of
      Hsp90AA1 in cow bearing mutant allele C was higher (4.18 +/- 0.928) than cows
      bearing wild-type allele G (1.008 +/- 0.0.129) in stress season. In summary,
      there was an association between genetic variations in the Hsp90AA1 and
      thermoresistance. This association could be used as a marker in genetic selection
      for heat tolerance in Chinese Holstein cattle breeds.

PMID- 29353405
TI  - Correction to: Voriconazole-induced periostitis deformans: serial imaging in a
      patient with ANCA vasculitis.
AB  - The original version of this paper unfortunately contained mistakes in the
      affiliations for all authors.

PMID- 29353404
TI  - DNA methylation rather than single nucleotide polymorphisms regulates the
      production of an aberrant splice variant of IL6R in mastitic cows.
AB  - Interleukin-6 receptor-alpha (IL6R) interacts with IL6 and forms a ligand
      receptor complex, which can stimulate various cellular responses, such as cell
      proliferation, cell differentiation, and activation of inflammatory processes.
      Both genetic mutation and epigenetic modification regulate gene transcription. We
      identified a novel splice variant of bovine IL6R, designated as IL6R-TV, which is
      characterized by the skipping of exon 2 of the NCBI-referenced IL6R gene (IL6R
      reference). The expression levels of IL6R-TV and IL6R-reference transcripts were
      lower in normal mammary gland tissues. These transcripts play a potential role
      during inflammatory infection. We also detected two putative functional SNPs
      (g.19711 T > C and g.19731 G > C) located within the upstream 100 bp of exon 2.
      These SNPs formed two haplotypes (T-G and C-C). Two mutant pSPL3 exon-trapping
      plasmids (pSPL3-T-G and pSPL3-C-C) were transferred into the bovine mammary
      epithelial cells (MAC-T) and human embryonic kidney 293 T cells (HEK293T) to
      investigate the relationship between the two SNPs and the aberrant splicing of
      IL6R. DNA methylation levels of the alternatively spliced exon in normal and
      mastitis-infected mammary gland tissues were quantified through nested bisulfate
      sequencing PCR (BSP) and cloning sequencing. We found that DNA methylation
      regulated IL6R transcription. The DNA methylation level was high in mastitis
      infected mammary gland tissues and stimulated IL6R expression, thereby promoting
      the inclusion of the alternatively spliced exon. The upregulated expression of
      the two transcripts was due to DNA methylation modification rather than genetic
      mutations.

PMID- 29353406
TI  - Case report: vertebral foreign body granuloma mimicking a skeletal metastasis.
AB  - Intraosseous foreign body granuloma formation related to migrated surgical
      material is a rarely reported condition with variable imaging appearance. In this
      case report, we describe a foreign body granuloma that occurred in a lumbar
      vertebral body one level above a prior surgical fusion. The lytic appearance
      mimicked a skeletal metastasis in a 65-year-old patient with recently diagnosed
      renal cell carcinoma. To the best of our knowledge, this is the first reported
      case of a lumbar vertebral foreign body granuloma occurring distant from the site
      of surgery, indistinguishable from skeletal metastasis on radiologic examination.

PMID- 29353407
TI  - Role of the petrous ridge and angulation of the trigeminal nerve in the
      pathogenesis of trigeminal neuralgia, with implications for microvascular
      decompression.
AB  - INTRODUCTION: Vascular compression is the main pathogenetic factor in apparently
      primary trigeminal neuralgia; however some patients may present with clinically
      classical neuralgia but no vascular conflict on MRI or even at surgery. Several
      factors have been cited as alternative or supplementary factors that may cause
      neuralgia. This work focuses on the shape of the petrous ridge at the point of
      exit from the cavum trigeminus as well as the angulation of the nerve at this
      point. METHODS: Patients with trigeminal neuralgia that had performed a complete
      imagery workup according to our protocol and had microvascular decompression were
      included as well as ten controls. In all subjects, the angle of the petrous ridge
      as well as the angle of the nerve on passing over the ridge were measured. These
      were compared from between the neuralgic and the non-neuralgic side and with the
      measures performed in controls. RESULTS: In 42 patients, the bony angle of the
      petrous ridge was measured to be 86 degrees  on the neuralgic side, significantly
      more acute than that of controls (98 degrees , p = 0.004) and with a trend to be
      more acute than the non-neuralgic side (90 degrees , p = 0.06). The angle of the
      nerve on the side of the neuralgia was measured to be on average 141 degrees ,
      not significantly different either from the other side (144 degrees , p = 0.2) or
      from controls (142 degrees , p = 0.4). However, when taking into account the
      grade of the conflict, the angle was significantly more acute in patients with
      grade II/III conflict than on the contralateral side, especially when the
      superior cerebellar artery was the conflicting vessel. CONCLUSION: This pilot
      study analyzes factors other than NVC that may contribute to the pathogenesis of
      the neuralgia. It appears that aggressive bony edges may contribute-at least
      indirectly-to the neuralgia. This should be considered for surgical indication
      and conduct of surgery when patients undergo MVD.

PMID- 29353408
TI  - Clinical applications of dynamic CT angiography for intracranial lesions.
AB  - BACKGROUND: Dynamic CT angiography (dCTA) augments traditional CTA with temporal
      resolution and has been demonstrated to influence operative planning in skull
      base surgery. METHODS: Three hundred twenty-five dynamic CTA cases from a single
      institution were reviewed for indication of study, findings, and comparison to
      other modalities of imaging. RESULTS: The most frequent application of dCTA was
      pre-operative surgical planning (59.4%); resection of skull base tumors
      represented the majority of these pre-operative studies (93.3%). It was also used
      to evaluate new neurological symptoms (20.9%). Of these, the most common symptoms
      prompting a dCTA study included headache (22.1%) and visual field deficit
      (11.8%). The most commonly visualized vascular lesions were partial (22.9%) and
      complete vascular occlusions (9.0%). Dynamic CTA has also been useful in post
      operative imaging for vascular malformations (9.5%) and tumors (2.5%). Finally,
      dCTA was employed to evaluate ambiguous abnormal findings observed on other
      imaging modalities (7.7%). Cerebral dCTA ruled out inconclusive abnormal vascular
      findings visualized on other imaging modalities (64.0%) more frequently than it
      confirmed them (32.0%), and was inconclusive in a singular case (4.0%).
      CONCLUSIONS: Cerebral dCTA is an evolving new technology with a diverse spectrum
      of potential applications. In addition to its role in guiding pre-operative
      planning for skull base surgical cases, dynamic CTA offers excellent spatial and
      temporal resolution for assessment of vascular lesions.

PMID- 29353409
TI  - 16S rRNA gene sequencing reveals altered composition of gut microbiota in
      individuals with kidney stones.
AB  - Nephrolithiasis is a common urological disease with high prevalence and
      recurrence rates. Characterizing gut microbiome profiles of nephrolithiasis
      patients may provide valuable insights and potential biomarkers for the disease.
      Therefore, we explored the relation between gut microbiome and nephrolithiasis
      using 16S ribosomal RNA (rRNA) gene sequencing. 13 patients with multiple kidney
      stones and 13 matched healthy controls were recruited. A decreasing trend in
      number of observed species in nephrolithiasis patients was detected, although
      statistical significance was not reached (p = 0.086). The inter-group variability
      in community structure by beta diversity analysis showed a clear separation
      between nephrolithiasis patients and healthy controls. Twenty genera
      differentiated significantly in relative abundance between nephrolithiasis
      patients and healthy controls (all p < 0.05). Among the 20 genera,
      Phascolarctobacterium, Parasutterella, Ruminiclostridium_5,
      Erysipelatoclostridium, Fusicatenibacter and Dorea were correlated with the
      concentration of the trace elements in blood, including potassium, sodium,
      calcium and chlorinum. Characteristic microbiome in nephrolithiasis patients was
      also identified by linear discriminant analysis effect size (LEfSe). These
      findings may provide novel and non-invasive potential diagnostic biomarkers for
      nephrolithiasis, and contribute to prevention and treatment of nephrolithiasis
      from the perspective of maintaining micro-ecological equilibrium in gut.

PMID- 29353412
TI  - Helicobacter pylori LPS-induced gastric mucosal spleen tyrosine kinase (Syk)
      recruitment to TLR4 and activation occurs with the involvement of protein kinase
      Cdelta.
AB  - Spleen tyrosine kinase (Syk) has emerged recently as a major effector of
      proinflammatory genes expression induced by LPS-elicited TLR4 activation, and
      manifested by the up-amplification in the production of inflammatory mediators,
      including PGE2 and NO. Here, we investigated the nature of factors involved in
      the recruitment and interaction of Syk with TLR4 in gastric mucosa in response to
      H. pylori LPS. We show that stimulation of gastric mucosal cells with the LPS
      leads to localization of Syk with the membrane-associated TLR4 complex and its
      activation through phosphorylation on Tyr. Furthermore, we reveal that the
      membrane translocation of Syk upon the LPS stimulation occurs with the
      involvement of protein kinase Cdelta (PKCdelta)-mediated phosphorylation of Syk
      on Ser. Thus, our findings demonstrate that H. pylori LPS-induced up-regulation
      in Syk activity proceeds through the stage of PKCdelta-mediated Syk
      phosphorylation on Ser, required for its recruitment to the membrane-anchored
      TLR4, followed by the kinase activation through phosphorylation on Tyr. Hence,
      the phase of PKCdelta-mediated Syk phosphorylation on Ser affects the extent of
      amplification in gastric mucosal inflammatory response to H. pylori.

PMID- 29353414
TI  - Oral Administration of Compound Probiotics Ameliorates HFD-Induced Gut Microbe
      Dysbiosis and Chronic Metabolic Inflammation via the G Protein-Coupled Receptor
      43 in Non-alcoholic Fatty Liver Disease Rats.
AB  - The aim of this study was to investigate how the effects of compound probiotics
      modulate the gut microbiota, short-chain fatty acid (SCFA), body composition,
      serum and liver lipids, and inflammatory markers in non-alcoholic fatty liver
      disease (NAFLD) rats. Twenty-four male SD rats were randomly divided into 3
      groups: normal control group (standard feed), high-fat diet (HFD) feeding group
      (83% standard feed + 10% lard oil + 1.5% cholesterol + 0.5% cholate + 5%
      sucrose), and compound probiotics intervention group (HFD + 0.6 g * kg-1 * d-1
      compound probiotics). The microbial population was assessed by 16S rDNA
      amplification and sequence analysis. Body composition, serum and liver lipids,
      serum inflammatory markers, colonic SCFAs, and relative proteins were assessed.
      The results showed that compound probiotics significantly reduced body weight,
      visceral and total fat mass, and the levels of hepatic TC and TG and serum TG,
      FFA, ALT, LPS, IL-1beta, and IL-18 (P < 0.05). The proportions of TM7 phylum
      (0.06 vs 1.57%, P < 0.05) clearly increased, while that of Verrucomicrobia phylum
      (5.69 vs 2.61%, P < 0.05) clearly decreased. Compound probiotics also increased
      the representation of Ruminococcus genus (0.95 vs 1.83%, P < 0.05), while the
      proportion of Veillonella genus decreased (0.10 vs 0.03%, P < 0.05). The levels
      of colonic SCFAs and GPR43, NLRP3, ASC, and CASPASE-1 proteins also changed
      significantly (P < 0.05). Compound probiotics modulated gut microbiota, SCFAs,
      and their receptor GPR43 in NAFLD rats. These changes might inhibit lipid
      deposition and chronic metabolic inflammation in response to the insult of HFD.

PMID- 29353413
TI  - Exploring the genetic and adaptive diversity of a pan-Mediterranean crop wild
      relative: narrow-leafed lupin.
AB  - KEY MESSAGE: This first pan-Mediterranean analysis of genetic diversity in wild
      narrow-leafed lupin revealed strong East-West genetic differentiation of
      populations, an historic eastward migration, and signatures of genetic adaptation
      to climatic variables. Most grain crops suffer from a narrow genetic base, which
      limits their potential for adapting to new challenges such as increased stresses
      associated with climate change. Plant breeders are returning to the wild
      ancestors of crops and their close relatives to broaden the genetic base of their
      crops. Understanding the genetic adaptation of these wild relatives will help
      plant breeders most effectively use available wild diversity. Here, we took
      narrow-leafed lupin (Lupinus angustifolius L.) as a model to understand
      adaptation in a wild crop ancestor. A set of 142 wild accessions of narrow-leafed
      lupin from across the Mediterranean basin were subjected to genotyping-by
      sequencing using Diversity Arrays Technology. Phylogenetic, linkage
      disequilibrium and demographic analyses were employed to explore the history of
      narrow-leafed lupin within the Mediterranean region. We found strong genetic
      differentiation between accessions from the western and eastern Mediterranean,
      evidence of an historic West to East migration, and that eastern Mediterranean
      narrow-leafed lupin experienced a severe and recent genetic bottleneck. We showed
      that these two populations differ for flowering time as a result of local
      adaptation, with the West flowering late while the East flowers early. A genome
      wide association study identified single nucleotide polymorphism markers
      associated with climatic adaptation. Resolving the origin of wild narrow-leafed
      lupin and how its migration has induced adaptation to specific regions of the
      Mediterranean serves as a useful resource not only for developing narrow-leafed
      lupin cultivars with greater resilience to a changing climate, but also as a
      model which can be applied to other legumes.

PMID- 29353415
TI  - Investigation of Lactic Acid Bacteria Isolated from Giant Panda Feces for
      Potential Probiotics In Vitro.
AB  - The present study aimed to isolate an optimal lactic acid bacterial strain from
      the feces of healthy giant pandas. The strain exhibited good stability at low pH
      and high bile salt concentrations, activity against pathogens relevant to pandas,
      and antibiotic susceptibility. In the current study, 25 isolates were obtained
      from de Man, Rogosa, and Sharpe agar. Two (E21 and G83) and eight (E1, E2, E16,
      E18, E21, E69, E70, and G83) isolates demonstrated good performance at pH 2.0 and
      bile 2% (w/v), respectively. Three isolates (G83, G88, and G90) possessed better
      antimicrobial effect on enterotoxigenic Escherichia coli CVCC196 (ETEC) than the
      rest. One isolate (G83) strongly affected Salmonella, whereas three (G83, G87,
      and G88) exhibited inhibitory activity against Staphylococcus aureus. All
      isolates were multi-drug resistant. These isolates were identified as
      Lactobacillus (5 isolates) and Enterococcus (20 isolates) by 16S rRNA sequencing.
      Virulence genes were detected in Enterococcus isolates. Isolate G83 was
      identified as Lactobacillus plantarum and was considered as the best probiotic
      candidate among all of the experimental isolates. This study provided necessary
      and important theoretical guidance for further experiments on G83 in vivo.

PMID- 29353416
TI  - Physicians' decision about long-term thromboprophylaxis in cancer outpatients:
      CAT AXIS, a case vignette study on clinical practice in France.
AB  - PURPOSE: Data on long-term venous thromboembolism prophylaxis in cancer
      outpatients remain scarce. In the absence of clear and consistent treatment
      guidelines, our objectives were to describe and better understand clinical
      practice and to identify factors influencing the use of thromboprophylaxis.
      METHODS: CAT AXIS was a multicentred cross-sectional study based on the
      completion of physician-profile questionnaires and the assessment of 10 e-mailed
      credible clinical scenarios of lung, colon and breast cancers by each of
      participants using the case vignette-validated method. RESULTS: A total of 224
      physicians participated allowing the completion and the analysis of 2085 reviewed
      case vignettes corresponding to 765, 703 and 617 fictive clinical scenarios on
      lung, colon and breast cancers, respectively. The overall rate of
      thromboprophylaxis was 680/2085 (32.6%) among participants with a comparable
      proportion for the three types of cancer. Low-molecular-weight heparin (LMWH) was
      the most frequently used, by 92.7, 93.8 and 83.9% of participants for lung, colon
      and breast cancers, respectively; thromboprophylaxis duration of >= 3 months was
      used by 74.4% of participants. Multivariate analyses revealed that the Eastern
      Cooperative Oncology Group index, metastatic malignancy, chemotherapy and history
      of thrombosis were significantly associated with the therapeutic decision unlike
      Khorana score and anaemia. CONCLUSION: In the absence of clear guidance, the use
      of thromboprophylaxis remains low and rather empiric even though the selection of
      LMWH by the majority of participants and treatment duration seems appropriate
      based on available data to date. Specific guidelines with corresponding awareness
      are required.

PMID- 29353417
TI  - Maternal metabolic response to dietary treatment for impaired glucose tolerance
      and gestational diabetes mellitus.
AB  - BACKGROUND: Dietary advice is a standard component of treatment for pregnant
      women with impaired glucose tolerance (IGT) and gestational diabetes (GDM), yet
      few studies report glycemic profiles in response to dietary therapies and the
      optimal dietary approach remains uncertain. AIM: To assess changes in maternal
      glycemic profile and pregnancy outcomes among women with diet-controlled IGT and
      GDM. METHODS: Pregnant women who had one or more elevated values on a 3-h oral
      glucose tolerance test were enrolled. All participants received dietary advice
      and glucose monitoring as part of routine clinical care. Fasting and 1-h post
      prandial blood samples, collected prior to initiation of clinical treatment and
      repeated 4-6 weeks later, were analyzed for glucose, insulin, and C-peptide.
      Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.
      Women who required pharmacological therapy for glucose control were excluded from
      analyses. RESULTS: Participants (N = 93) were of moderately older age (mean 33
      years), with a high rate of overweight/obesity (mean body mass index (BMI) =
      28.65 kg/m2), and were diagnosed late in gestation (mean 29 weeks). Fasting (mean
      +/- SD 4.82 +/- 0.53 to 4.60 +/- 0.42 mmol/l; p < 0.001) and post-prandial
      glucose (7.01 +/- 1.19 to 6.47 +/- 1.10; p = 0.004) decreased significantly
      following the intervention. Baseline HOMA-IR was elevated (3.12 +/- 1.03) but did
      not significantly decrease (2.78 +/- 1.52; p = 0.066). There were high rates of
      macrosomia (24.7%) and cesarean delivery (32.3%). CONCLUSIONS: Although
      improvements in blood glucose levels were observed among women with diet
      controlled IGT and GDM, this was insufficient to significantly affect insulin
      resistance or perinatal outcome. Late diagnosis and treatment of IGT/GDM may have
      contributed to such outcomes.

PMID- 29353418
TI  - Emerging trends in hospitalisation for fragility fractures in Ireland.
AB  - BACKGROUND: We analysed hospital admissions and bed occupancy for fragility
      fractures in Ireland over a 15-year period to assess fracture admission trends
      and to project admissions over the next three decades. METHODS: We used the
      Hospital In-Patient Enquiry (HIPE) scheme to extract data on fracture admissions
      to Irish hospitals between 2000 and 2014 inclusive. We calculated absolute
      numbers and age-standardised rates of hospitalisations for men and women >= 50
      years for each osteoporotic-type fracture. We projected fracture numbers and bed
      days using these trends, and associated costs to 2046 based on 2014 rates.
      RESULTS: The absolute number of all fragility fracture admissions increased by
      30% between 2000 and 2014, for both men (40%) and women (27%). In-patient bed
      days for osteoporotic fractures have increased by 51% in the same period. Hip
      fractures dominated admissions, accounting for 36.5% of all admissions and almost
      half (46.7%) of all bed days. Age-standardised rates of hip fracture admission
      decreased significantly (p < 0.001) in women, but not in men, while rates of non
      hip osteoporotic fracture admissions have not changed significantly for men or
      women. Hospitalisations for all osteoporotic fractures are projected to increase
      by 150% to 31,605 in 2046, 58% of whom will be 80 years or older. CONCLUSIONS:
      There has been a significant increase in the number of fracture admissions in
      Irish men and women over the past 15 years. This is projected to increase further
      over the next three decades which will place a significant burden on the Irish
      healthcare system.

PMID- 29353419
TI  - Pleiotropic effects of the wheat domestication gene Q on yield and grain
      morphology.
AB  - MAIN CONCLUSION: Transformation from q to Q during wheat domestication functioned
      outside the boundary of threshability to increase yield, grains m-2, grain weight
      and roundness, but to reduce grains per spike/spikelet. Mutation of the Q gene,
      well-known affecting wheat spike structure, represents a key domestication step
      in the formation of today's free-threshing, economically important wheats. In a
      previous study, multiple yield components and spike characteristics were
      associated with the Q gene interval in the bread wheat 'Forno' * European spelt
      'Oberkulmer' recombinant inbred line population. Here, we reported that this
      interval was also associated with grain yield, grains m-2, grain morphology, and
      spike dry weight at anthesis. To clarify the roles of Q in agronomic trait
      performance, a functional marker for the Q gene was developed. Analysis of
      allelic effects showed that the bread wheat Q allele conferred free-threshing
      habit, soft glumes, and short and compact spikes compared with q. In addition,
      the Q allele contributed to higher grain yield, more grains m-2, and higher
      thousand grain weight, whereas q contributed to more grains per spike/spikelet
      likely resulting from increased preanthesis spike growth. For grain morphology,
      the Q allele was associated with reduced ratio of grain length to height,
      indicating a rounder grain. These results are supported by analysis of four Q
      mutant lines in the Chinese Spring background. Therefore, the transition from q
      to Q during wheat domestication had profound effects on grain yield and grain
      shape evolution as well, being a consequence of pleiotropy.

PMID- 29353420
TI  - Properties of Antibiotic-Resistant Bacteria Isolated from Onsite Wastewater
      Treatment Plant in Relation to Biofilm Formation.
AB  - The aim of the present study was to determine some properties of antibiotic
      resistant bacterial strains isolated from onsite wastewater technology in
      relation to biofilm formation, e.g., autoaggregation and motility. Additionally,
      biosurfactant production by the isolates was also evaluated. The ability of
      selected strains to develop a biofilm was assessed by using the crystal violet
      method, which allows to indirectly quantify the attached bacterial biomass (live,
      dead cells, and polysaccharides as well). Obtained results showed that 19 of the
      analyzed strains were able to produce biofilm after 72 h of incubation. The low
      values of surface tension in the range between 28 and 36 mN/m were observed in
      the bacteria, which are not able to produce biofilm or be classified as weak
      biofilm producers. Among biofilm-forming strains the highest autoaggregation
      index was observed for Mycobacterium brumae and Bacillus alcalophilus.
      Noteworthy, that some strains capable of biofilm formation showed no aggregation
      abilities or were characterized by low autoaggregative properties. The results of
      visual autoaggregation assay showed no visible flocs after given time of
      incubation. The results from motility test demonstrated that most of the analyzed
      strains were motile. Noteworthy, that up to now literature data about physiology,
      biofilm formation, and autoaggregative capabilities of bacteria isolated from
      onsite wastewater technology are very limited and this paper gives the
      information on the antibiotic-resistant bacteria with ability to form biofilm.
      Thus, the present study points to develop novel bioinocula in antibiotic
      degradation and to reach novel biofilm-dispersing agents produced by various
      bacteria that can be used as disinfectants or surface-coating agents to prevent
      microbial surface colonization and biofilm development.

PMID- 29353421
TI  - 1-Day or 5-Day Fecal Samples, Which One is More Beneficial to be Used for DNA
      Based Gut Microbiota Study.
AB  - Fecal sample collection is an important influential factor for DNA-based gut
      microbiota study. It is controversial whether the microbiome detected in fecal
      sample collected at one random day could fully represent the gut microbial
      community. The aim of the study is to figure out whether the use of fecal sample
      mixture collected at consecutive 5 days could more accurately represent gut
      microbial community. 1- and 5-day fecal samples were collected from 8 healthy
      adults and analyzed by 16S rRNA sequence. Our results indicated that both 1-day
      fecal samples and 5-day samples exhibited relatively high repeatability. The
      relative abundance of majority of bacterial taxa did not changed between 1-day
      fecal samples and 5-day fecal samples. However, the alpha diversity of 5-day
      fecal samples was higher than that of 1-day fecal samples. When the aims of
      studies are to analyze the relative abundance of specific OTUs among subjects,
      fecal samples collected at one day could be used. When microbial diversity is one
      of essential factors to be analyzed, the use of 5-day fecal samples may be more
      recommended.

PMID- 29353422
TI  - Biomechanical in vitro comparison of suture anchors for thumb UCL repair.
AB  - Different types of intraosseous suture anchors can be used for thumb ulnar
      collateral ligament (UCL) repair surgery. Some of them have already been tested
      biomechanically in intact bone; however, there exists little knowledge of their
      stability when implanted in avulsion fracture. In this biomechanical in vitro
      study, three anchor types (hard, soft and novel BoneWelding) were tested on 24
      fresh frozen human thumbs from 12 body donors. After the repair of an iatrogenic
      ligamentous UCL rupture, the thumbs were cyclically loaded. A new set of anchors
      was implanted at the contralateral radial side of the same specimen into an
      iatrogenic avulsion fracture and pulled out of the bone. The most common mode of
      failure in ligamentous UCL repairs was the suture-ligament interface, especially
      when using soft anchors. In avulsion fractures, the novel anchor withstood
      significantly higher pullout forces than the hard or soft anchor (65 N vs. 42 N
      vs. 27 N; p = .006). The BW anchor provides sufficient anchorage in trabecular
      bone for UCL repair in case of avulsion fractures.

PMID- 29353423
TI  - Polymerase chain reaction-based detection of myc transduction in feline leukemia
      virus-infected cats.
AB  - Feline lymphomas are associated with the transduction and activation of cellular
      proto-oncogenes, such as c-myc, by feline leukemia virus (FeLV). We describe a
      polymerase chain reaction assay for detection of myc transduction usable in
      clinical diagnosis. The assay targets c-myc exons 2 and 3, which together result
      in a FeLV-specific fusion gene following c-myc transduction. When this assay was
      conducted on FeLV-infected feline tissues submitted for clinical diagnosis of
      tumors, myc transduction was detected in 14% of T-cell lymphoma/leukemias. This
      newly established system could become a useful diagnostic tool in veterinary
      medicine.

PMID- 29353424
TI  - Characterization of small RNAs originating from mitoviruses infecting the conifer
      pathogen Fusarium circinatum.
AB  - Deep sequencing of small RNAs has proved effective in the diagnosis of mycovirus
      infections. In this study, the presence of mycoviruses in ten isolates of the
      phytopathogenic fungus Fusarium circinatum was investigated by high-throughput
      sequencing (HTS) of small RNAs. The contigs resulting from de novo assembly of
      the reads were aligned to viral genome sequences. The presence of each mycovirus
      detected in the isolates was confirmed by RT-PCR analysis with four previously
      described primer pairs and seven new pairs designed on the basis of sequencing
      data. The findings demonstrate the potential use of HTS for reconstructing
      previously identified mitoviruses infecting F. circinatum.

PMID- 29353426
TI  - Is dipyrone effective as a preemptive analgesic in third molar surgery? A pilot
      study.
AB  - PURPOSE: Studies on preemptive analgesia in maxillofacial surgery have shown
      several controversial clinical results, mainly due to the absence of a
      methodological standard, besides a wide variety of studied drugs. This study
      intended to answer the following hypothesis: Is the administration of dipyrone
      preemptively capable of decreasing trans- and postoperative pain in the third
      molar surgical extraction? METHODS: A pilot prospective double-blind placebo
      controlled study was carried out with 25 patients submitted to the third molar
      surgical extraction at two moments, one side in each intervention. Dipyrone (1 g)
      was preemptively administered (study group) for the extraction of two third
      molars on the same side and, in a second surgical procedure, dipyrone (1 g) was
      administered in the immediate postoperative period (control group). Evaluated
      variables were the amount of anesthetic, pain perceived through the visual
      analogue scale (VAS) in transoperative and immediate postoperative periods, and
      over 12-h investigation period, analgesic consumption, duration of surgery, and
      time to rescue analgesia. RESULTS: The results were submitted to Student's t test
      and statistical differences were observed in transoperative (p < 0.05) and
      immediate postoperative (p < 0.01) periods, while the other studied variables did
      not present statistical differences. CONCLUSION: The preemptive administration of
      dipyrone decreased the perception of transoperative and immediate postoperative
      pain when compared to its use after surgery only.

PMID- 29353425
TI  - Natural attenuation of petroleum hydrocarbons-a study of biodegradation effects
      in groundwater (Vitanovac, Serbia).
AB  - The role of natural attenuation processes in groundwater contamination by
      petroleum hydrocarbons is of intense scientific and practical interest. This
      study provides insight into the biodegradation effects in groundwater at a site
      contaminated by kerosene (jet fuel) in 1993 (Vitanovac, Serbia). Total petroleum
      hydrocarbons (TPH), hydrochemical indicators (O2, NO3-, Mn, Fe, SO42-, HCO3-),
      delta13C of dissolved inorganic carbon (DIC), and other parameters were measured
      to demonstrate biodegradation effects in groundwater at the contaminated site.
      Due to different biodegradation mechanisms, the zone of the lowest concentrations
      of electron acceptors and the zone of the highest concentrations of metabolic
      products of biodegradation overlap. Based on the analysis of redox-sensitive
      compounds in groundwater samples, redox processes ranged from strictly anoxic
      (methanogenesis) to oxic (oxygen reduction) within a short distance. The
      dependence of groundwater redox conditions on the distance from the source of
      contamination was observed. delta13C values of DIC ranged from - 15.83 to -
      2.750/00, and the most positive values correspond to the zone under anaerobic and
      methanogenic conditions. Overall, results obtained provide clear evidence on the
      effects of natural attenuation processes-the activity of biodegradation
      mechanisms in field conditions.

PMID- 29353427
TI  - Application of three-dimensional printing in laparoscopic dissection to
      facilitate D3-lymphadenectomy for right colon cancer.

PMID- 29353428
TI  - Staplers for obstructed defecation syndrome.

PMID- 29353429
TI  - A sensitive method using SPME pre-concentration for the quantification of
      aromatic amines in indoor air.
AB  - Monitoring the levels of aliphatic and aromatic amines (AA) in indoor air is
      important to protect human health because of exposure to these compounds through
      diet and inhalation. A sampling and analytical method using XAD-2 cartridges and
      gas chromatography coupled to mass spectrometry used for assessing 25 AA in
      different smoking and non-smoking indoor environment was developed. After
      sampling and delivering 1 m3 of air (6-8 h sampling), an adsorbent was
      ultrasonically extracted with acetonitrile, concentrated to 1 mL and diluted in
      25 mL of water (pH = 9; 5% NaCl), and then extracted for 40 min at 80  degrees C
      using a divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber and
      injected in a GC/MS system. With this method, 22 of the 25 AA can be analyzed
      with detection limits up to five times lower than that of classic liquid
      injection. Benzylamine, 3-aminophenol, and 4-aminophenol were not detected with
      the solid-phase micro-extraction (SPME) method. It can be assumed that
      aminophenols required a derivatization step for their analysis by GC as these
      molecules were not detected regardless of the injection mode used. Graphical
      abstract Analysis of aromatic amines in indoor air by SPME-GC/MS.

PMID- 29353430
TI  - Multiplex highly sensitive immunochromatographic assay based on the use of
      nonprocessed antisera.
AB  - The format of an immunochromatographic multiassay is first proposed with native
      antisera and a universal conjugate of antispecies antibodies with gold
      nanoparticles. This format allows (1) the exclusion of purification and
      conjugation stages for specific antibodies and (2) significant reduction of the
      concentration of specific antibodies in the system. The independent use of
      specific antibodies and a conjugated marker provided a low detection limit and
      high signal intensity. The proposed format was implemented for the simultaneous
      detection of two herbicides. The instrumental limits for the detection of
      atrazine and chlorsulfuron were 0.1 and 0.7 ng/mL, respectively, and the analysis
      time was 20 min. The suitability of the test system for monitoring these
      herbicides in nontreated apple and blackcurrant juices is shown. The assay
      technique is simple, sensitive, and easily transferrable to any other antigen.
      Graphical abstract The proposed format of the immunochromatographic multiassay is
      based on the use of native antisera and a universal conjugate of antispecies
      antibodies with gold nanoparticles. In this way purification and conjugation
      stages for specific antibodies are excluded, and the concentrations of specific
      antibodies and the conjugated marker can be varied independently to obtain a low
      detection limit.

PMID- 29353431
TI  - Sensitive electrochemical detection of microRNA-21 based on propylamine
      functionalized mesoporous silica with glucometer readout.
AB  - A new homogeneous electrochemical sensing system was developed for sensitive
      detection of microRNA-21 (miRNA-21) based on target-induced glucose release from
      propylamine-functionalized mesoporous silica nanoparticle (MSN) with glucometer
      readout. Glucose molecules (as the signal tracers) were initially gated into the
      pores through the interaction of the negatively charged anchor DNA with the
      aminated MSN. Upon addition of target miRNA, the analyte competitively hybridized
      with anchor DNA to form the RNA-DNA duplex, thus resulting in detachment of
      anchor DNA from the MSN accompanying the pore opening. The loaded glucose
      molecules released out from the pores because of concentration gradients, which
      could be detected by using a portable personal glucometer (PGM). Experimental
      results indicated that the PGM signal increased with the increasing miRNA level,
      and exhibited a good linear dependence on the miRNA-21 concentration from 50 pM
      to 5.0 nM with a detection limit of 19 pM under optimum conditions. Additionally,
      multifunctional mesoporous silica nanoparticles also showed good stability and
      favorable selectivity, and satisfactory accuracy for the miRNA detection in cell
      lysates with quantitative real-time polymerase chain reaction (qRT-PCR). Such
      good analytical performance endows it as a promising scheme for the efficient and
      convenient detection of miRNA in clinical diagnosis and therapy. Graphical
      abstract An electrochemical sensing system is designed for detection of microRNA
      21 based on target-induced glucose release from propylamine-functionalized
      mesoporous silica nanoparticle with glucometer readout.

PMID- 29353432
TI  - Post-translational modifications in tumor biomarkers: the next challenge for
      aptamers?
AB  - Advances in proteomics have fueled the search for novel cancer biomarkers with
      higher selectivity. Differential expression of low abundant proteins has been the
      usual way of finding those biomarkers. The existence of a selective receptor for
      each biomarker is compulsory for their use in diagnostic/prognostic assays.
      Antibodies are the receptors of choice in most cases although aptamers are
      becoming familiar because of their facile and reproducible synthesis, chemical
      stability as well as comparable affinity and selectivity. In recent years, it has
      been reported that the pattern of post-translational modifications, altered under
      neoplastic disease, is a better predictive biomarker than the total protein
      level. Among others, abnormal glycosylation is attracting great attention.
      Lectins and antibodies are being used for identification and detection of the
      carbohydrate moiety with low level of discrimination among various glycoproteins.
      Such level of selectivity is critical to bring next-generation biomarkers to the
      clinic. Aptamers that can be rationally tailored for a certain molecule domain
      can become the golden receptor to specifically detect aberrant glycosylation at
      each protein or even at each glycosylation site, providing new diagnostic tools
      for early detection of cancer. Graphical abstract Aptamers may specifically
      differentiate normal from aberrant glycoproteins.

PMID- 29353433
TI  - Recent trends and analytical challenges in plant bioactive peptide separation,
      identification and validation.
AB  - Interest in research into bioactive peptides (BPs) is growing because of their
      health-promoting ability. Several bioactivities have been ascribed to peptides,
      including antioxidant, antihypertensive and antimicrobial properties. As they can
      be produced from precursor proteins, the investigation of BPs in foods is
      becoming increasingly popular. For the same reason, production of BPs from by
      products has also emerged as a possible means of reducing waste and recovering
      value-added compounds suitable for functional food production and supplements.
      Milk, meat and fish are the most investigated sources of BPs, but vegetable
      derived peptides are also of interest. Vegetables are commonly consumed, and agro
      industrial wastes constitute a cheap, large and lower environmental impact source
      of proteins. The use of advanced analytical techniques for separation and
      identification of peptides would greatly benefit the discovery of new BPs. In
      this context, this review provides an overview of the most recent applications in
      BP investigations for vegetable food and by-products. The most important issues
      regarding peptide isolation and separation, by single or multiple chromatographic
      techniques, are discussed. Additionally, problems connected with peptide
      identification in plants and non-model plants are discussed regarding the
      particular case of BP identification. Finally, the issue of peptide validation to
      confirm sequence and bioactivity is presented. Graphical representation of the
      analytical workflow needed for investigation of bioactive peptides and applied to
      vegetables and vegetable wastes Graphical Abstract.

PMID- 29353434
TI  - Prediction of progression in skull base meningiomas: additional benefits of
      apparent diffusion coefficient value.
AB  - A subset of benign (WHO grade I) skull base meningiomas show early
      progression/recurrence (P/R) in the first years after surgical resection.
      Besides, complete surgical resection may be difficult to achieve safely in skull
      base meningiomas due to complex neurovascular structures. The one main challenge
      in the treatment of skull base meningiomas is to determine factors that correlate
      with P/R. We retrospectively investigated the preoperative CT and MR imaging
      features for the prediction of P/R in skull base meningiomas, with emphasis on
      quantitative ADC values. Only patients had postoperative MRI follow-ups for more
      than 1 year (at least every 6 months) were included. From October 2006 to
      December 2015, total 73 patients diagnosed with benign (WHO grade I) skull base
      meningiomas were included (median follow-up time 41 months), and 17 (23.3%)
      patients had P/R (median time to P/R 28 months). Skull base meningiomas with
      spheno-orbital location, adjacent bone invasion, high DWI, and lower ADC
      value/ratio were significantly associated with P/R (P < 0.05). The cut-off points
      of ADC value and ADC ratio for prediction of P/R are 0.83 * 10- 3 mm2/s and 1.09
      respectively, with excellent area under curve (AUC) values (0.86 and 0.91) (P <
      0.05). In multivariate logistic regression, low ADC values (< 0.83 * 10- 3 mm2/s)
      and adjacent bone invasion are high-risk factors of P/R (P < 0.05), with odds
      ratios of 31.53 and 17.59 respectively. The preoperative CT and MRI features for
      prediction of P/R offered clinically vital information for the planning of
      treatment in skull base meningiomas.

PMID- 29353435
TI  - Letter to the editor: local alkylating chemotherapy applied immediately after 5
      ALA guided resection of glioblastoma does not provide additional benefit.

PMID- 29353437
TI  - Correction to: The Compassionate Side of Neuroscience: Tony Sermone's Undiagnosed
      Genetic Journey-ADNP Mutation.
AB  - The original version of this article unfortunately contained mistakes.

PMID- 29353436
TI  - Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life
      Clinical Experience.
AB  - BACKGROUND: Precision treatment of cancer uses biomarker-driven therapy to
      individualize and optimize patient care. OBJECTIVE: To evaluate real-life
      clinical experience with biomarker-driven therapy in metastatic gastric and
      esophageal cancer in Israel. PATIENTS AND METHODS: This multicenter retrospective
      cohort study included patients with metastatic gastric or esophageal cancer who
      were treated in the participating institutions and underwent biomarker-driven
      therapy. Treatment was considered to have a benefit if the ratio between the
      longest progression-free survival (PFS) post biomarker-driven therapy and the
      last PFS before the biomarker-driven therapy was >=1.3. The null hypothesis was
      that <=15% of patients gain such benefit. RESULTS: The analysis included 46
      patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors).
      At least one actionable (i.e., predictive of response to a specific therapy)
      biomarker was identified for each patient. Immunohistochemistry was performed on
      all samples and identified 1-8 (median: 3) biomarkers per patient (most commonly:
      low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the
      biomarker analysis (1-4 lines). In the 1st line after biomarker analysis, five
      patients (18%) achieved a partial response and five (18%) stable disease; the
      median (range) PFS was 129 (12-1155) days. Twenty-four patients were evaluable
      for PFS ratio analysis; in seven (29.2%), the ratio was >=1.3. In a one-sided
      exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null
      hypothesis was rejected. CONCLUSIONS: Our findings demonstrated that implementing
      biomarker-driven analysis is feasible and could provide clinical benefit for a
      considerable proportion (~30%) of patients with metastatic gastric or esophageal
      cancer.

PMID- 29353438
TI  - Examination of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) as a
      Potential Biomarker in Heart Failure Patients.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic and
      multifunctional neuropeptide having neurotrophic, neuroprotective, and general
      cytoprotective actions in a variety of tissues based on its anti-apoptotic, anti
      inflammatory, and antioxidant effects. Several studies have demonstrated its
      cardioprotective effects in vitro and in various animal models. However, few data
      are available on the presence of PACAP in human cardiac tissues and its role in
      the pathomechanism and progression of different cardiac disorders, particularly
      heart failure. Earlier, our research group has shown PAC1 receptor
      immunoreactivity in human heart tissue samples and we have found significantly
      elevated PACAP27- and PACAP38-like immunoreactivity in ischemic cardiac samples
      compared to valvular abnormalities with radioimmunoassay. In the last few years,
      numerous studies examined the presence and the changes of PACAP levels in
      different human tissue samples and biological fluids to show alterations in
      different physiological and pathological conditions. Therefore, the aim of the
      present study was to measure the alterations of blood PACAP levels in chronic
      heart failure caused by primary dilated cardiomyopathy or ischemic cardiomyopathy
      and to examine the possible relationship between serum levels of PACAP, N
      terminal prohormone of brain natriuretic peptide (NT-proBNP), and systolic left
      ventricular function, the most reliable biomarkers of heart failure. In the group
      of mild heart failure patients, a significant strong negative correlation was
      detected. Furthermore, in moderate heart failure, we found a significant moderate
      negative correlation between PACAP and NT-proBNP levels only in ischemic
      subgroup. Positive correlation was found between serum PACAP level and ejection
      fraction only in patients with heart failure due to ischemic cardiomyopathy but
      not in patients with primary dilated cardiomyopathy. In summary, remarkable
      differences were observed between the ischemic and non-ischemic heart failure
      suggesting that PACAP might play an important role in the pathomechanism and
      progression of ischemic heart failure and it might be a potential biomarker of
      cardiac diseases in the future.

PMID- 29353439
TI  - Transgenesis by microparticle bombardment for live imaging of fluorescent
      proteins in Pristionchus pacificus germline and early embryos.
AB  - Pristionchus pacificus is a free-living nematode used as a model organism for
      evolutionary developmental and ecological biology. Although a transgenic
      technique to form complex arrays by microinjection has been established in P.
      pacificus, transgene expression from the array in the germline and early embryos
      tends to be silenced. Here, we established a method to integrate transgenes into
      the genome of P. pacificus using microparticle bombardment with hygromycin B
      selection. Additionally, we isolated a mutant exhibiting significantly lower
      autofluorescence in the germline and early embryos, facilitating visualization of
      transgene-derived fluorescent proteins for live imaging. Transgenic lines
      constructed using these tools successfully expressed GFP-tagged proteins in the
      germline and early embryos and enabled live imaging of chromosomes, microtubules,
      and centrosomes.

PMID- 29353441
TI  - Pre- and postoperative management of risk factors for postoperative delirium: who
      is in charge and what is its essence?
AB  - Postoperative delirium (POD) is an adverse clinical outcome characterized by
      cognitive, affective and behavioral symptoms with typically an acute onset and a
      fluctuating course. POD is attributed to certain patients' predisposing factors
      as well as to treatment-related precipitating factors. While there are several
      single-component interventions for the prevention of POD, evolving evidence
      suggests the importance of a system approach in the prevention of POD. This
      involves strategies by multidisciplinary teams with additional geriatric
      consultation services to identify risk factors for POD and to modify their impact
      on the perioperative course. Some patients may profit from postponing an elective
      surgery and undergoing a prehabilitation program to optimize his/her resilience
      for the surgical and anesthesiologic stressors.

PMID- 29353440
TI  - Healthy lifestyle promotion in primary schools through the board game Kaledo: a
      pilot cluster randomized trial.
AB  - : The board game Kaledo was proven to be effective in improving nutrition
      knowledge and in modifying dietary behavior in students attending middle and high
      school. The present pilot study aims to reproduce these results in younger
      students (7-11 years old) attending primary school. A total of 1313 children from
      ten schools were recruited to participate in the present study. Participants were
      randomized into two groups: (1) the treatment group which consisted of playing
      Kaledo over 20 sessions and (2) the no intervention group. Anthropometric
      measures were carried out for both groups at baseline (prior to any treatment)
      and at two follow-up post-assessments (8 and 18 months). All the participants
      completed a questionnaire concerning physical activity and a 1-week food diary at
      each assessment. The primary outcomes were (i) BMI z-score, (ii) scores on
      physical activity, and (iii) scores on a dietary questionnaire. BMI z-score was
      significantly lower in the treated group compared to the control group at 8
      months. Frequency and duration of self-reported physical activity were also
      significantly augmented in the treated group compared to the control group at
      both post-assessments. Moreover, a significant increase in the consumption of
      healthy food and a significant decrease in junk food intake were observed in the
      treated group. CONCLUSION: The present results confirm the efficacy of Kaledo in
      younger students in primary schools, and it can be used as a useful nutritional
      tool for obesity prevention programs in children. What is Known: * Kaledo is a
      new educational board game to improve nutrition knowledge and to promote a
      healthy lifestyle. * In two cluster randomized trials conducted in Campania
      region (Italy), we showed that Kaledo could improve nutrition knowledge and
      dietary behavior and have a positive effect on the BMI z-score in children with
      age ranging from 9 to 14 years old attending school. * Kaledo may be used as an
      effective tool for obesity prevention programs in middle and high school
      students. What is New: * Investigating the effects of Kaledo on younger primary
      school children (7-11 year olds), Kaledo could be an effective tool in obesity
      prevention programs for children as young as 7 years old.

PMID- 29353442
TI  - Flexible pseudotyping of retrovirus using recombinase-mediated cassette exchange.
AB  - OBJECTIVE: Develop an engineered cell line containing two flexible gene
      expression systems enabling the continuous production of tailor-made recombinant
      gammaretrovirus with predictable productivities through targeted integration.
      RESULTS: Dual-FLEX cells (dFLEX) contain two independent recombinase-mediated
      cassette exchange (RMCE) systems which confer flexibility to the expression of
      different transgene and envelope combinations. The flexible envelope expression
      in dFLEX cells was validated by pseudotyping retrovirus particles with three
      different viral envelope proteins-GaLV, 4070A and VSV-G. Our results show that
      dFLEX cells are able to provide high titers of infectious retroviral particles
      with a single-copy integration of the envelope constructs after RMCE. The
      integrated CRE/Lox tagging cassette was amenable to express envelope proteins
      both using constitutive (i.e. CMV) and inducible (i.e. Tet-on) promoters.
      CONCLUSIONS: dFLEX cell line provides predictable productivities of recombinant
      retrovirus pseudotyped with different envelope proteins broadening the tropism of
      particles that can be generated and thus accelerating the research and
      development of retrovirus-based products.

PMID- 29353443
TI  - Role of Fluorescent In Situ Hybridization, Cholangioscopic Biopsies, and EUS-FNA
      in the Evaluation of Biliary Strictures.
AB  - BACKGROUND AND AIMS: Our goal was to compare the diagnostic accuracy of FISH in
      the detection of malignancy compared with other standard diagnostic modalities,
      including brush cytology and biopsy specimens over a 10-year period of
      prospective data collection. METHODS: We conducted a review of all consecutive
      biliary strictures evaluated between 2006 and 2016. Patients with a final
      pathologic diagnosis or conclusive follow-up were included. We evaluated the
      performance of FISH polysomy (CEP 3, 7, and 17) and 9p21 deletion as well as
      cholangioscopic biopsy (CBx) and EUS-FNA. Statistical analysis was performed with
      the Mann-Whitney U and Fisher's exact tests. RESULTS: Of 382 patients with
      indeterminate strictures, 281 met inclusion criteria. Forty-nine percent were
      malignant. Cytology, FISH polysomy, and FISH polysomy/9p21 showed a specificity
      of 99.3%. FISH polysomy/9p21 as a single modality was the most sensitive at 56%
      (p < 0.001). The sensitivity of FISH polysomy/9p21 and cytology was significantly
      higher than cytology alone at 63 versus 35% (p < 0.05). EUS-FNA for distal
      strictures and CBx for proximal strictures increased sensitivity from 33 to 93%
      (p < 0.001) and 48-76% (p = 0.05) in cytology-negative strictures. CONCLUSIONS:
      The high specificity of FISH polysomy/9p21 suggests that a positive result is
      sufficient for diagnosing malignancy in indeterminate strictures. The
      significantly higher sensitivity of FISH polysomy/9p21 compared to cytology
      supports the use of FISH in all non-diagnostic cases. Although both EUS-FNA and
      CBx were complimentary, our results suggest that distal strictures should be
      evaluated by EUS initially. Proximal strictures may be evaluated by FISH first
      and then by CBx if inconclusive.

PMID- 29353444
TI  - Mortality Is Rare Following Elective and Non-elective Surgery for Ulcerative
      Colitis, but Mild Postoperative Complications Are Common.
AB  - BACKGROUND DATA: Currently, data regarding the rates of morbidity and mortality
      following non-elective colectomy for ulcerative colitis (UC) are variable. We
      sought to determine the rates and predictors of 90-day mortality and
      complications following colectomy for UC. METHODS: Patients undergoing an initial
      surgery for UC at a tertiary care center between January 2002 and January 2014
      were included. Patients were identified using ICD-9 code 556.x. Each record was
      manually reviewed for demographic information, medical histories, UC history,
      medications, and data regarding the admission and discharge. Charts were reviewed
      for mortality and complications within 90 days of surgery. Complications were
      classified using the Clavien-Dindo classification system. Univariate and
      multivariate analyses were performed using IBM SPSS Statistics, version 23.0.
      RESULTS: Two hundred and fifty-eight patients underwent surgery for UC. 69% were
      elective, and 31% were urgent/emergent. There were no deaths reported within 30
      days of surgery. At 90 days, there were 2 deaths in the elective group and 1
      death in the urgent/emergent group. The death in the urgent/emergent group was
      likely related to the initial surgery, while the elective group death was not
      directly related to the initial surgery for UC. Complications occurred in 47% of
      patients. There were no significant differences in rates of complications in
      either surgical cohort. Majority (62%) of the complications were Clavien-Dindo
      grade 1 or 2 with no difference in the elective or urgent/emergent group.
      Unplanned readmissions occurred in 24% of cases. CONCLUSION: Surgery for UC is
      not associated with any mortality at 30 days and very low mortality at 90 days.
      However, surgery is associated with an increased rate of minor postoperative
      complications and readmissions.

PMID- 29353445
TI  - Hypermethylation of NF-kappaB-Activating Protein-Like (NKAPL) Promoter in
      Hepatocellular Carcinoma Suppresses Its Expression and Predicts a Poor Prognosis.
AB  - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a complicated disease with
      low survival rate partially due to frequent recurrence and no efficient therapy.
      Promoter hypermethylation of tumor suppressor genes has been demonstrated as one
      of the molecular mechanisms contributing to tumorigenesis and progression in HCC.
      This study aims to investigate regulation of NKAPL expression by promoter
      methylation and its clinical relevance as a biomarker for HCC. METHODS: We
      measured mRNA expression of NKAPL in 5 HCC cell lines and a cohort of 62 pairs of
      primary HCC tumor and their adjacent non-cancer liver tissues. NKAPL protein
      expression on HCC cell lines and clinical samples was assessed by Western blot
      and immunohistochemistry, respectively. Association analyses between NKAPL
      expression and clinicopathologic characteristics in the cohort were conducted.
      Methylation statuses of NKAPL promoter in 18 pairs of tumor and adjacent non
      tumor HCC samples were studied using methylation-specific PCR. Biological
      functions of NKAPL in HCC were investigated by ectopic expression of NKAPL in HCC
      cells, and cell viability and cell cycle analyses were performed. RESULTS: Our
      present study showed suppressed expression and promoter hypermethylation are
      common events in HCC. Demethylation experiment in HCC cells demonstrated that the
      NKAPL expression was regulated by promoter methylation. In addition, high
      methylation level of NKAPL and its low expression predict poor outcome.
      Furthermore, ectopic expression of NKAPL in the HCC cells inhibited cell growth.
      CONCLUSIONS: Our findings suggest that methylation of NKAPL is a frequent event
      and is a potential prognosis biomarker in HCC.

PMID- 29353446
TI  - Disentangling Somatosensory Evoked Potentials of the Fingers: Limitations and
      Clinical Potential.
AB  - In searching for clinical biomarkers of the somatosensory function, we studied
      reproducibility of somatosensory potentials (SEP) evoked by finger stimulation in
      healthy subjects. SEPs induced by electrical stimulation and especially after
      median nerve stimulation is a method widely used in the literature. It is
      unclear, however, if the EEG recordings after finger stimulation are reproducible
      within the same subject. We tested in five healthy subjects the consistency and
      reproducibility of responses through bootstrapping as well as test-retest
      recordings. We further evaluated the possibility to discriminate activity of
      different fingers both at electrode and at source level. The lack of consistency
      and reproducibility suggest responses to finger stimulation to be unreliable,
      even with reasonably high signal-to-noise ratio and adequate number of trials. At
      sources level, somatotopic arrangement of the fingers representation was only
      found in one of the subjects. Although finding distinct locations of the
      different fingers activation was possible, our protocol did not allow for non
      overlapping dipole representations of the fingers. We conclude that despite its
      theoretical advantages, we cannot recommend the use of somatosensory potentials
      evoked by finger stimulation to extract clinical biomarkers.

PMID- 29353448
TI  - 1H, 13C and 15N NMR assignments of cyclophilin LRT2 (OsCYP2) from rice.
AB  - Cyclophilins are enzymes that catalyze the isomerization of a prolyl-peptide bond
      and are found in both prokaryotes and eukaryotes. LRT2 (also known as OsCYP2) is
      a cyclophilin in rice (Oryza sativa), that has importance in lateral root
      development and stress tolerance. LRT2 is 172 amino acids long and has a
      molecular weight of 18.3 kDa. Here, we report the backbone and sidechain
      resonance assignments of 1H, 13C, 15N in the LRT2 protein using several 2D and 3D
      heteronuclear NMR experiments at pH 6.7 and 298 K. Our chemical shift data
      analysis predicts a secondary structure like the cytosolic wheat cyclophilin
      TaCypA-1 with 87.7% sequence identity. These assignments will be useful for
      further analysis in the NMR studies for function and structure of this enzyme.

PMID- 29353447
TI  - The combined pN stage and breast cancer subtypes in breast cancer: a better
      discriminator of outcome can be used to refine the 8th AJCC staging manual.
AB  - BACKGROUND: pN stage and breast cancer subtypes (BCS) are both well-recognized
      prognostic indicators. Our previous work has highlighted that patients even with
      the same pN stage exhibited a significant survival difference in different BCS.
      Given this achievement, we hypothesized that a statistical interaction might
      exist between pN stage and BCS. The aim of this retrospective cohort study was to
      compare the prognostic value of the combined pN stage and BCS (pNnew stage) with
      either pN stage or BCS alone, and to determine if this combined new stage could
      serve as an alternative discriminator of outcome. METHODS: We combined pN stage
      and BCS to create a new variable named pNnew stage and then divided it into four
      groups: pN0new, pN1new, pN2new, and pN3new. Survival analysis was performed with
      the use of the Kaplan-Meier method and the log-rank test was used for univariate
      analysis. For multivariate analysis, cox proportional hazard models were applied,
      allowing for the estimation of disease-free survival (DFS). To assess
      discriminatory accuracy of the models, we compared the area under the receiver
      operating characteristic curve (AUROC), the Akaike information criterion (AIC),
      and the Bayesian information criterion (BIC) values. Then, we used this pNnew
      stage to generate a TNnewM staging system according to the 7th AJCC staging
      system. RESULTS: A statistical interaction between pN stage and BCS was found. In
      multivariate survival analysis, the pNnew stage has been confirmed as an
      independent prognostic variable of 5-year DFS. The pNnew stage, with a smaller
      AIC or BIC value and larger AUROC, was a more powerful predictor of DFS than
      either pN stage or BCS alone. Results were validated in a separate cohort of
      patients. The TNnewM stage proposed in our present study was found comparable to
      the new 8th AJCC edition which includes anatomic T, N, and M plus tumor grade and
      the status of the biomarkers Her-2, ER, and PR with respect to prognostic value
      for breast cancer patients. CONCLUSIONS: The pNnew stage (combined pN stage and
      BCS) appears to be a more powerful predictor and discriminator for the outcome of
      breast cancer, as compared to pN stage or BCS alone, and the TNnewM stage may
      serve as a simple, easy-to-use alternative to the 8th AJCC edition staging
      manual.

PMID- 29353449
TI  - Blastulation timing is associated with differential mitochondrial content in
      euploid embryos.
AB  - PURPOSE: Preimplantation genetic screening (PGS) and assessment of mitochondrial
      content (MC) are current methods for selection of the best embryos for transfer.
      Studies suggest that time-lapse morphokinetics (TLM) may also be helpful for
      selecting embryos more likely to implant. In our study, we sought to examine the
      relationship between TLM parameters and MC to determine if they could be used
      adjunctively in embryo selection. We also examined the relationship between MC
      with ploidy and blastulation. METHODS: Cryopreserved human embryos at the zygote
      stage were thawed and cultured in a time-lapse system. Blastomere and
      trophectoderm biopsies were performed on days 3 and 6. Biopsied cells and all
      whole embryos from day 6 were analyzed for MC (ratio of mitochondrial to nuclear
      DNA) and ploidy using next-generation sequencing. RESULTS: In embryos, MC per
      cell declined between day 3 and day 6. While early cleavage parameters did not
      predict MC, embryos with longer blastulation timing had higher MC on day 6. Day 6
      MC was lower in euploid vs. aneuploid embryos and lower in blastocysts vs.
      arrested embryos. CONCLUSIONS: A lower MC at the blastocyst stage was associated
      with euploid status and blastocyst formation, indicating better embryo quality
      compared to those with a higher MC. Higher MC in aneuploid and arrested embryos
      may be explained by slower cell division or degradation of genomic DNA over time.
      Blastulation timing may be helpful for selection of higher quality embryos.
      Combining blastulation timing and MC along with morphologic grading and euploid
      status may offer a new direction in embryo selection.

PMID- 29353451
TI  - Analysis of Circulating Mediators of Bone Remodeling in Prader-Willi Syndrome.
AB  - We tested the hypothesis that the levels of bone remodeling mediators may be
      altered in Prader-Willi syndrome (PWS). We assessed RANKL, OPG, sclerostin, DKK-1
      serum levels, and bone metabolism markers in 12 PWS children (7.8 +/- 4.3 years),
      14 PWS adults (29.5 +/- 7.2 years), and 31 healthy controls matched for sex and
      age. Instrumental parameters of bone mineral density (BMD) were also evaluated.
      Lumbar spine BMD Z-scores were reduced in PWS children (P < 0.01), reaching
      osteopenic levels in PWS adults. PWS patients showed lower 25(OH)-vitamin D serum
      levels than controls (P < 0.001). Osteocalcin was increased in PWS children but
      reduced in adults respect to controls (P < 0.005 and P < 0.01, respectively).
      RANKL levels were higher in both pediatric and PWS adults than controls (P <
      0.004), while OPG levels were significantly reduced (P < 0.004 and P < 0.006,
      respectively). Sclerostin levels were increased in children (P < 0.04) but
      reduced in adults compared to controls (P < 0.01). DKK-1 levels did not show
      significant difference between patients and controls. In PWS patients, RANKL,
      OPG, and sclerostin significantly correlated with metabolic and bone instrumental
      parameters. Consistently, with adjustment for age, multiple linear regression
      analysis showed that BMD and osteocalcin were the most important predictors for
      RANKL, OPG, and sclerostin in children, and GH and sex steroid replacement
      treatment in PWS adults. We demonstrated the involvement of RANKL, OPG, and
      sclerostin in the altered bone turnover of PWS subjects suggesting these
      molecules as markers of bone disease and new potential pharmacological targets to
      improve bone health in PWS.

PMID- 29353452
TI  - Random regression analysis for body weights and main morphological traits in
      genetically improved farmed tilapia (Oreochromis niloticus).
AB  - To genetically analyse growth traits in genetically improved farmed tilapia
      (GIFT), the body weight (BWE) and main morphological traits, including body
      length (BL), body depth (BD), body width (BWI), head length (HL) and length of
      the caudal peduncle (CPL), were measured six times in growth duration on 1451
      fish from 45 mixed families of full and half sibs. A random regression model
      (RRM) was used to model genetic changes of the growth traits with days of age and
      estimate the heritability for any growth point and genetic correlations between
      pairwise growth points. Using the covariance function based on optimal RRMs, the
      heritabilities were estimated to be from 0.102 to 0.662 for BWE, 0.157 to 0.591
      for BL, 0.047 to 0.621 for BD, 0.018 to 0.577 for BWI, 0.075 to 0.597 for HL and
      0.032 to 0.610 for CPL between 60 and 140 days of age. All genetic correlations
      exceeded 0.5 between pairwise growth points. Moreover, the traits at initial days
      of age showed less correlation with those at later days of age. With phenotypes
      observed repeatedly, the model choice showed that the optimal RRMs could more
      precisely predict breeding values at a specific growth time than repeatability
      models or multiple trait animal models, which enhanced the efficiency of
      selection for the BWE and main morphological traits.

PMID- 29353450
TI  - Cancer Treatment and Bone Health.
AB  - Considerable advances in oncology over recent decades have led to improved
      survival, while raising concerns about long-term consequences of anticancer
      treatments. In patients with breast or prostate malignancies, bone health is a
      major issue due to the high risk of bone metastases and the frequent prolonged
      use of hormone therapies that alter physiological bone turnover, leading to
      increased fracture risk. Thus, the onset of cancer treatment-induced bone loss
      (CTIBL) should be considered by clinicians and recent guidelines should be
      routinely applied to these patients. In particular, baseline and periodic follow
      up evaluations of bone health parameters enable the identification of patients at
      high risk of osteoporosis and fractures, which can be prevented by the use of
      bone-targeting agents (BTAs), calcium and vitamin D supplementation and
      modifications of lifestyle. This review will focus upon the pathophysiology of
      breast and prostate cancer treatment-induced bone loss and the most recent
      evidence about effective preventive and therapeutic strategies.

PMID- 29353453
TI  - Optimization of biodiesel synthesis by esterification using a fermented solid
      produced by Rhizopus microsporus on sugarcane bagasse.
AB  - A fermented solid containing lipases was produced by solid-state fermentation of
      Rhizopus microsporus on sugarcane bagasse enriched with urea, soybean oil, and a
      mineral solution. The dry fermented solid produced using R. microsporus (RMFS)
      was used to catalyze the synthesis of alkyl-esters by esterification in a solvent
      free system containing ethanol and oleic acid (as a model system) or a mixture of
      fatty acids obtained from the physical hydrolysis of soybean soapstock acid oil
      (FA-SSAO) in subcritical water. The conversions were 93.5 and 84.1%, for oleic
      acid and FA-SSAO, respectively, at 48 h and 40  degrees C, at a molar ratio (MR)
      of ethanol to fatty acid of 5:1. A further increase in the MR to 10:1 improved
      the production of ethylic-esters, giving conversions at 48 h of 98 and 86% for
      oleic acid and FA-SSAO, respectively. The results obtained in this work foster
      further studies on scaling-up of an environmentally friendly process to produce
      biofuels.

PMID- 29353454
TI  - Acute-Phase Plasma Osteopontin as an Independent Predictor for Poor Outcome After
      Aneurysmal Subarachnoid Hemorrhage.
AB  - Experimental studies reported that osteopontin (OPN), a matricellular protein, is
      induced in brain after subarachnoid hemorrhage (SAH). The aim of this study was
      to investigate the relationships between plasma OPN levels and outcome after
      aneurysmal SAH in a clinical setting. This is a prospective study consisting of
      109 aneurysmal SAH patients who underwent aneurysmal obliteration within 48 h of
      SAH. Plasma OPN concentrations were serially determined at days 1-3, 4-6, 7-9,
      and 10-12 after onset. Various clinical factors as well as OPN values were
      compared between patients with 90-day good and poor outcomes. Plasma OPN levels
      were significantly higher in SAH patients compared with control patients and
      peaked at days 4-6. Poor-outcome patients had significantly higher plasma OPN
      levels through all sampling points. Receiver-operating characteristic curves
      demonstrated that OPN levels at days 10-12 were the most useful predictor of poor
      outcome at cutoff values of 915.9 pmol/L (sensitivity, 0.694; specificity,
      0.845). Multivariate analyses using the significant variables identified by day 3
      showed that plasma OPN >= 955.1 pmol/L at days 1-3 (odds ratio, 10.336; 95%
      confidence interval, 2.563-56.077; p < 0.001) was an independent predictor of
      poor outcome, in addition to increasing age, preoperative World Federation of
      Neurological Surgeons grades IV-V, and modified Fisher grade 4. Post hoc analyses
      revealed no correlation between OPN levels and serum levels of C-reactive
      protein, a non-specific inflammatory parameter, at days 1-3. Acute-phase plasma
      OPN could be used as a useful prognostic biomarker in SAH.

PMID- 29353455
TI  - The Interplay Between Apolipoprotein E4 and the Autophagic-Endocytic-Lysosomal
      Axis.
AB  - Since its discovery as a genetic risk factor for Alzheimer's disease, the APOE4
      allele has been linked to the majority of the pathological findings associated
      with the disease progression. These include abnormalities of the endocytic,
      autophagic, and lysosomal machineries, which begin at the most early stages of
      Alzheimer's disease development. Considering that these three vesicular systems
      share common features and, in fact, comprise an interconnected cargo-trafficking
      and degradation network, some of the effects of APOE4 are interrelated, while
      others are system-specific. In turn, APOE4-driven impairments of endocytosis,
      autophagy, and lysosomal activity influence various aspects of Alzheimer's
      disease pathology, ranging from Abeta generation and clearance to neuronal loss
      and cognitive deficits. This review discusses the detrimental effects of APOE4 on
      the endocytic-autophagic-lysosomal axis in the context of Alzheimer's disease, as
      well as the various mechanisms underlying them.

PMID- 29353456
TI  - In Vivo Transient and Partial Cell Reprogramming to Pluripotency as a Therapeutic
      Tool for Neurodegenerative Diseases.
AB  - In theory, human diseases in which a specific cell type degenerates, such as
      neurodegenerative diseases, can be therapeutically addressed by replacement of
      the lost cells. The classical strategy for cell replacement is exogenous cell
      transplantation, but now, cell replacement can also be achieved with in situ
      reprogramming. Indeed, many of these disorders are age-dependent, and
      "rejuvenating" strategies based on cell epigenetic modifications are a possible
      approach to counteract disease progression. In this context, transient and/or
      partial reprogramming of adult somatic cells towards pluripotency can be a
      promising tool for neuroregeneration. Temporary and controlled in vivo
      overexpression of Yamanaka reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc
      (OSKM)) has been proven feasible in different experimental settings and could be
      employed to facilitate in situ tissue regeneration; this regeneration can be
      accomplished either by producing novel stem/precursor cells, without the
      challenges posed by exogenous cell transplantation, or by changing the epigenetic
      adult cell signature to the signature of a younger cell. The risk of this
      procedure resides in the possible lack of perfect control of the process,
      carrying a potential oncogenic or unexpected cell phenotype hazard. Recent
      studies have suggested that these limits can be overcome by a tightly controlled
      cyclic regimen of short-term OSKM expression in vivo that prevents full
      reprogramming to the pluripotent state and avoids both tumorigenesis and the
      presence of unwanted undifferentiated cells. On the other hand, this strategy can
      enhance tissue regeneration for therapeutic purposes in aging-related
      neurological diseases as well. These data could open the path to further research
      on the therapeutic potential of in vivo reprogramming in regenerative medicine.

PMID- 29353458
TI  - Outcome of unexplained acute respiratory distress syndrome with diffuse alveolar
      damage after lung transplantation.

PMID- 29353457
TI  - Fasting and Fast Food Diet Play an Opposite Role in Mice Brain Aging.
AB  - Fasting may be exploited as a possible strategy for prevention and treatment of
      several diseases such as diabetes, obesity, and aging. On the other hand, high
      fat diet (HFD) represents a risk factor for several diseases and increased
      mortality. The aim of the present study was to evaluate the impact of fasting on
      mouse brain aging transcriptome and how HFD regulates such pathways. We used the
      NCBI Gene Expression Omnibus (GEO) database, in order to identify suitable
      microarray datasets comparing mouse brain transcriptome under fasting or HFD vs
      aged mouse brain transcriptome. Three microarray datasets were selected for this
      study, GSE24504, GSE6285, and GSE8150, and the principal molecular mechanisms
      involved in this process were evaluated. This analysis showed that, regardless of
      fasting duration, mouse brain significantly expressed 21 and 30 upregulated and
      downregulated genes, respectively. The involved biological processes were related
      to cell cycle arrest, cell death inhibition, and regulation of cellular
      metabolism. Comparing mouse brain transcriptome under fasting and aged
      conditions, we found out that the number of genes in common increased with the
      duration of fasting (222 genes), peaking at 72 h. In addition, mouse brain
      transcriptome under HFD resembles for the 30% the one of the aged mice.
      Furthermore, several molecular processes were found to be shared between HFD and
      aging. In conclusion, we suggest that fasting and HFD play an opposite role in
      brain transcriptome of aged mice. Therefore, an intermittent diet could represent
      a possible clinical strategy to counteract aging, loss of memory, and
      neuroinflammation. Furthermore, low-fat diet leads to the inactivation of brain
      degenerative processes triggered by aging.

PMID- 29353459
TI  - Adjuvant therapies in critical care: music therapy.

PMID- 29353460
TI  - Psychological burnout and critical care medicine: big threat, big opportunity.

PMID- 29353461
TI  - Eye blinks are related to auditory information processing: evidence from a
      complex speech perception task.
AB  - There is increasing evidence that spontaneous eye blinks are related to mental
      states and can predict performance in certain tasks because of their relation to
      dopaminergic activity. Moreover, it has been shown that eye blinks while
      performing visual tasks are preferably executed not before all available
      information and even the manual response has been processed and given. Thus,
      blinks provide a natural endpoint of visual information processing. In the
      present study, we investigate to what degree such functional assignment of eye
      blinks also applies when only auditory stimuli are processed. For that, we
      present blink analyses on data of an auditory stock price monitoring task to
      examine the timing and frequency of blinks relative to the temporal dynamics of
      the task and different kinds of available cues. Our results show that blinks are
      meaningfully rather than randomly paced, although no visual information has to be
      processed. Blinks are significantly accelerated if a no-go trial is indicated
      which made all the subsequent information irrelevant. Although the stimuli were
      exclusively auditory, blinks were mostly inhibited during stimulus presentation.
      Taken together, blinks depend on the information being presented and mark a
      distinct point in time at which this information is conclusively processed. These
      findings deliver further support for the usefulness of eyeblink analyses,
      independently of the modality of the information being processed.

PMID- 29353462
TI  - Lactobacillus kosoi sp. nov., a fructophilic species isolated from koso, a
      Japanese sugar-vegetable fermented beverage.
AB  - A novel Gram-positive, fructophilic, catalase negative, and rod-shaped strain,
      designated strain 10HT was isolated from koso, a Japanese sugar-vegetable
      fermented beverage obtained from a food processing factory in Saku City, Nagano
      Prefecture, Japan. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed strain 10HT to belong to the genus Lactobacillus, with closely related
      type strains being Lactobacillus kunkeei YH-15T (95.5% sequence similarity),
      Lactobacillus ozensis Mizu2-1T (95.4% sequence similarity), and Lactobacillus
      apinorum Fhon13NT (95.3% sequence similarity). The isolate was found to grow at
      18-39  degrees C (optimum 27  degrees C), pH 4.0-7.0 (optimum pH 6.5) and in the
      presence of 0-2% NaCl (optimum 0% NaCl). The G + C content of its genomic DNA was
      determined to be 30.5 mol%. The major fatty acid (>= 10%) components identified
      included C16:0, C19:0 cyclo omega7c, C19:0 cyclo omega9c, and C18:1 omega9c. The
      polar lipids were identified as lysophosphatidylethanolamine,
      phosphatidylethanolamine and glycolipids. The predominant isoprenoid quinones (>
      10%) were identified as MK-7, MK-8, MK-9 and MK-10. The amino acid composition of
      the cell wall was detected as comprising Asp, Glu, Ala, and Lys but the strain
      lacks meso-diaminopimelic acid. As with other fructophilic lactic acid bacteria,
      such as L. kunkeei and L. apinorum, strain 10HT was found to prefer D-fructose to
      D-glucose as a growth substrate. On the basis of these genetic and phenotypic
      results, the isolate is concluded to represent a novel species, for which the
      name Lactobacillus kosoi is proposed. The type strain is 10HT (= NBRC 113063T =
      BCRC 81100T).

PMID- 29353463
TI  - Protective effect of a newly developed fucose-deficient recombinant antithrombin
      against histone-induced endothelial damage.
AB  - Antithrombin is expected to modulate both prothrombotic and proinflammatory
      reactions in sepsis; vascular endothelium is the primary target. In the present
      study, we sought to evaluate the protective effects of a newly developed fucose
      deficient recombinant antithrombin. Endothelial cells were treated in vitro with
      histone H4 to induce cellular damage. Low to high doses of either plasma-derived
      antithrombin or recombinant thrombomodulin were used as treatment interventions.
      Morphological change, apoptotic rate, cell viability, cell injury, and syndecan-4
      level in the medium were evaluated. Immunofluorescent staining with anti-syndecan
      4 was also performed. Both types of antithrombin reduced cellular damage and
      apoptotic cell death. Both plasma-derived and recombinant antithrombin improved
      cell viability and reduced cellular injury when administered at a physiological
      concentration or higher. Syndecan-4 staining became evident after treatment with
      histone H4, and both antithrombins suppressed the staining intensity at similar
      levels. The syndecan-4 level in the medium was significantly decreased by both
      antithrombins. None of the indicators showed a significant difference between
      plasma-derived and recombinant antithrombin. In conclusion, both recombinant and
      plasma-derived antithrombin can protect vascular endothelial cells. Recombinant
      antithrombin may represent a useful new therapeutic agent for sepsis-associated
      vascular damage.

PMID- 29353464
TI  - Laparoscopic -2port Varicocelectomy with Scarless Periumblical Mini-Incision:
      Initial Experience in Approach and Outcomes.
AB  - PURPOSE: As with other areas, there have been many efforts for minimally invasive
      surgery in varicocelectomy. We present our initial experience with laparoscopic
      varicocelectomy with a two-port scarless periumbilical mini-incision. MATERIALS
      AND METHODS: The study enrolled 18 patients who underwent laparoscopic
      varicocelectomy with a twoportscarless periumbilical mini-incision from February
      2012 to April 2013. The laparoscopic varicocelectomy was performed using two 5-mm
      ports at periumbilical sites in skin creases. Here, the surgical procedure is
      introduced and the outcomes of the case series are summarized. We reviewed other
      laparoscopic techniques and compared them with our technique. RESULTS: The mean
      patient age was 34.8 years. Of the 18 patients, 15 had grade 3 varicoceles. The
      mean operatingtime was 62.5 minutes. Postoperatively, the scrotal pain level
      decreased immediately from a mean VAS score of 6.3 to 4.4 and then to 1.7 by 24
      hours postoperatively. The mean hospital stay was 2.8 days. Complications
      included one hydrocele and two recurrent varicoceles. The operating time
      decreased as the surgeon's experience increased. CONCLUSION: Laparoscopic
      varicocelectomy with a two-port scarless periumbilical mini-incision is a
      feasible technique that can be mastered relatively easily. Prospective and
      comparative studies are required to validate this new technique.

PMID- 29353465
TI  - Assessment of Cross-correlations Between Selected Macromolecules in Urine of
      Children with Idiopathic Hypercalciuria.
AB  - PURPOSE: The aim of the study was assessment of four selected macromolecules
      level: osteopontin, calgranulin, uromodulin and bikunin in fresh morning urine
      sample in children with nephrolithiasis in the course of idiopathic
      hypercalciuria. MATERIALS AND METHODS: The study included 90 subjects aged from
      12 months to 18 years. The study group comprised 57 subjects- children with
      urinary tract lithiasis in the course of idiopathic hypercalciuria and the
      control group - 33 healthy children with no history of urolithiasis.
      Determinations of osteopontin, calgranulin, uromodulin and bikunin levels in the
      first morning urine were performed. RESULTS: The study group had a significantly
      decreased osteopontin excretion and significantly increased bikuninexcretion, and
      increased, however statistically nonsignificant, calgranulin excretion in
      comparison with the control group. Uromodulin excretion did not differ between
      groups. In both groups a statistically significant positive correlation was
      observed between uromodulin and bikunin levels. CONCLUSION: Children with urinary
      tract lithiasis in the course of idiopathic hypercalciuria reveal a different
      distribution of the study proteins than a healthy population.

PMID- 29353466
TI  - Inter-observer Agreement between Urologists and Radiologists in Interpreting the
      Computed Tomography Images of Emergency Patients with Renal Colic.
AB  - PURPOSE: Low-dose non-enhanced computed tomography (LDCT) has been shown to
      provide low radiation exposure with proper diagnostic accuracy compared to
      standard dose non-enhanced computed tomography (SDCT) in patients with renal
      colic. The goal of our study is to estimate the accuracy of LDCT and SDCT
      interpretation by emergency medicine residents who primarily treated patients
      with renal colic. MATERIALS AND METHODS: Thirty sample images of both LDCT and
      SDCT from renal colic patients were extracted from January 2013 to December 2015
      in a tertiary teaching hospital. Five emergency medicine residents interpreted60
      image samples over a time span of 3 weeks. The presence of a ureteric stone, the
      stone's size and location, and signs of obstruction were recorded in the reports.
      A total of 300 reports were compared with formal readingsby a radiologist. The
      inter-observer agreement and kappa value were calculated for comparative
      analysis. RESULTS: Identification of ureteric stones showed almost perfect inter
      observer agreement on SDCT (kappa value: 0.93), and the percentage of agreement
      was 96.7%. However, on LDCT, the inter-observer agreement was substantial (kappa
      value: 0.73), and the percentage of agreement was 88.0%. CONCLUSION: Using SDCT,
      emergency medicine residents had almost perfect inter-observer agreement in
      interpreting the CT images of patients with renal colic compared to a
      radiologist. However, when using LDCT, they had a lower inter-observer agreement.

PMID- 29353467
TI  - High Resolution Melting Analysis for Rapid Detection of PIK3CA Gene Mutations in
      Bladder Cancer: A Mutated Target for Cancer Therapy.
AB  - PURPOSE: PIK3CA gene mutations have clinical importance and their presence is
      associated with therapy response. They are also considered as a molecule for
      targeted therapy. As regards to their importance, genetic variation within a
      population as well as among different populations, this study was conducted to
      detect common mutations of exons 9 and 20 and other probable mutations in PIK3CA
      gene as well as their frequencies in Iranian bladder cancer patients. MATERIALS
      AND METHODS: Paired tumor and adjacent normal tissues samples were obtained from
      50 bladder cancer patients. Mutations of PIK3CA gene were detected using High
      Resolution Melting (HRM) analysis which is ahighly sensitive, repeatable, rapid,
      and cost-effective technique. To determine the precision of the HRM analysis,
      Sanger sequencing analysis was used. RESULTS: The result showed that mutations
      were present in 10% (5/50) of the subjects. The majority of these cases (4/5) had
      the mutation(s) in exon 9, spanning over five different mutations, among which
      three of them were actually novel mutations. Further analysis showed that 2 cases
      had simultaneous mutations for exon 9. In addition to novel mutations, the PIK3CA
      mutation rate observed in Iranian bladder patients was not as frequent as
      previous reports and COSMIC. CONCLUSION: HRM can be used as a rapid and sensitive
      method for mutation screening. Dysregulation of PIK3CA gene in bladder cancer
      reveals its potentials as a mechanistic link for cancer development, which in
      turn suggests its special use in interventional studies for targeted therapy.

PMID- 29353468
TI  - Corrigendum: Fat harvest using a closed-suction drain.
AB  - [This corrects the article on p. 288 in vol. 43.].

PMID- 29353469
TI  - Management of chronic hepatitis B patients in immunetolerant phase: what latest
      guidelines recommend.
AB  - The natural history of chronic hepatitis B (CHB) is complex and may run through
      different immune phases that may overlap. In particulars, the immune-tolerant
      phase is the most interesting and not as well understood as we thought. The
      concept of true immune tolerance have been under challenged from immunology
      points of view. The major international guidelines have not yet reached a
      consensus on the definition of the immune-tolerant phase. While positive
      hepatitis B e antigen (HBeAg), high serum hepatitis B virus (HBV) DNA and normal
      serum alanine aminotransferase (ALT) levels are the three key features of this
      phase, some guidelines also put age into consideration. A new nomenclature, Phase
      1 or HBeAg-positive chronic HBV infection, is given by the latest European
      Association for the Study of the Liver (EASL) published in April 2017. While
      current guidelines advise against starting antiviral treatment for immune
      tolerant CHB patients, some new data suggest treating such patients may reduce
      the risk of liver fibrosis progression and hepatocellular carcinoma.

PMID- 29353470
TI  - Screening of Pesticide and Biocide Patterns As Risk Drivers in Sediments of Major
      European River Mouths: Ubiquitous or River Basin-Specific Contamination?
AB  - Pesticides and biocides (PaB) are ubiquitously present in aquatic ecosystems due
      to their widespread application and have been detected in rivers at
      concentrations that may cause distress to aquatic life. Many of these compounds
      accumulate in sediments acting as long-term source for aquatic ecosystems.
      However, data on sediment contamination with current-use PaB in Europe are
      scarce. Thus, in this study, we elucidated PaB patterns and associated risks in
      sediments of seven major European rivers focusing on their last stretch as an
      integrative sink of particles transported by these rivers. Sediments were
      extracted with pressurized liquid extraction (PLE) using a broad-spectrum method
      recovering many compound classes with a wide range of physicochemical properties.
      Altogether 126 compounds were analyzed and 81 of them were detected with LC-HRMS
      and GC-NCI-MS/MS at least in one of the sediments. The highest number of
      compounds was detected (59) in River Elbe sediments close to Cuxhaven with
      outstanding concentrations ranging from 0.8 to 1691 mg/g organic carbon.
      Multivariate analysis identified a cluster with 3 ubiquitous compounds
      (cyhalothrin, carbendazim, fenpropimorph) and three clusters of chemicals with
      higher variability within and between rivers. Risk assessment indicates an acute
      toxic risk to benthic crustaceans at all investigated sites with the pyrethroids
      tefluthrin and cyfluthrin together with the fungicide carbendazim as the main
      drivers. Risks to algae were driven at most sites almost exclusively by
      photosynthesis inhibitors with estuary-specific herbicide mixtures, while in the
      rivers Po and Gironde cell division inhibitors played an important role at some
      sites. Mixtures of specific concern have been defined and suggested for
      integration in future monitoring programs.

PMID- 29353471
TI  - Strategy for an Association Study of the Intestinal Microbiome and Brain
      Metabolome Across the Lifespan of Rats.
AB  - There is increased appreciation for the diverse roles of the microbiome-gut-brain
      axis on mammalian growth and health throughout the lifespan. Numerous studies
      have demonstrated that the gut microbiome and their metabolites are extensively
      involved in the communication between brain and gut. Association study of brain
      metabolome and gut microbiome is an active field offering large amounts of
      information on the interaction of microbiome, brain and gut but data size and
      complicated hierarchical relationships were found to be major obstacles to the
      formation of significant, reproducible conclusions. This study addressed a two
      level strategy of brain metabolome and gut microbiome association analysis of
      male Wistar rats in the process of growth, employing several analytical platforms
      and various bioinformatics methods. Trajectory analysis showed that the age
      related brain metabolome and gut microbiome had similarity in overall alteration
      patterns. Four high taxonomical level correlated pairs of "metabolite type
      bacterial phylum", including "lipids-Spirochaetes", "free fatty acids (FFAs)
      Firmicutes", "bile acids (BAs)-Firmicutes", and "Neurotransmitters
      Bacteroidetes", were screened out based on unit- and multivariant correlation
      analysis and function analysis. Four groups of specific "metabolite-bacterium"
      association pairs from within the above high level key pairs were further
      identified. The key correlation pairs were validated by an independent animal
      study. This two-level strategy is effective in identifying principal correlations
      in big data sets obtained from the systematic multiomics study, furthering our
      understanding on the lifelong connection between brain and gut.

PMID- 29353472
TI  - Precise Measurement of the Hydrogen Isotope Composition of Phyllosilicates by
      Continuous Flow Off-Axis Integrated Cavity Output Spectroscopy.
AB  - New methodology is presented for analyzing hydrogen isotope ratios (D/H) in
      phyllosilicate minerals by laser absorption spectroscopy. D/H measurements were
      carried out using an off-axis integrated cavity output spectroscopy (OA-ICOS)
      instrument operated in a continuous flow configuration. Water was extracted from
      minerals in a high temperature quartz column and advanced to the analyzer in a
      dry air carrier gas stream. We report the first D/H measurements by a laser
      system for serpentine, muscovite, sericite, talc, and biotite. We also measure
      kaolinite, gypsum, and small volumes of water. Materials, excluding biotite, were
      calibrated to within 1.50/00 of IRMS-measured deltaDVSMOW values, with an average
      precision of 1.10/00. Biotite deltaD measurements were up to 100/00 more positive
      than established IRMS values, due to partial reduction of evolved waters by Fe in
      the high temperature column. We provide recommendations for overcoming redox
      interference for measurements of biotite, and other ferrous materials, by OA
      ICOS. Rapid, precise, and accurate analyses were carried out on water volumes as
      low as 0.25 MUL extracted from minerals. With the exception of talc, the time
      required for thermal dewatering and measurement is 140 s, which translates into a
      throughput of up to 6 mineral samples per hour, including replicates. By
      demonstrating high precision, rapid throughput, low cost, and ease of operation,
      we provide a tool that should enable researchers at institutions with limited
      funding to routinely measure D/H in hydrous minerals. The protocols presented
      herein should also be useful to commercial users seeking to produce high density
      isotope data sets relevant to exploration of hydrothermal ore deposits and
      geothermal fields.

PMID- 29353474
TI  - Four Hapten Spacer Sites Modulating Class Specificity: Nondirectional
      Multianalyte Immunoassay for 31 beta-Agonists and Analogues.
AB  - Immunoassay methods are important for monitoring beta-agonists illegally used for
      reducing animal fat deposition in livestock. However, there is no simultaneous
      screening surveillance immunoassay for detecting various beta-agonist chemicals
      that are possibly present in food. In this study, through the use of an R-(-)
      salbutamol derivative as the immunizing hapten, an antibody recognizing 31 beta
      agonists and analogues was generated for the first time. Three-dimensional
      quantitative structure-activity relationship (3D QSAR) revealed that strong
      steric and hydrophobic fields around the hapten spacer near C-2, as well as a
      chirality at C-1', dominantly modulated the class specificity of the raised
      antibody. However, a hapten spacer linked at C-2' or C-1 would lead to a narrow
      specificity, and the spacer charge at C-6 could affect the raised antibody
      specificity spectrum. A class specificity competitive indirect enzyme-linked
      immunosorbent assay (ciELISA) was established with an ideal recovery ranging from
      81.8 to 118.3% based on the obtained antibody. With a good agreement to the
      HPLC/MS method, the proposed ciELISA was confirmed to be reliable for the rapid
      surveillance screening assay of beta-agonists in urine. This investigation will
      contribute to the rational design and control of the immunoassay specificity.

PMID- 29353473
TI  - Electrochemiluminescence for Electric-Driven Antibacterial Therapeutics.
AB  - The employment of physical light sources in clinical photodynamic therapy (PDT)
      system endows it with a crucial defect in the treatment of deeper tissue lesions
      due to the limited penetration depth of light in biological tissues. In this
      work, we constructed for the first time an electric driven luminous system based
      on electrochemiluminescence (ECL) for killing pathogenic bacteria, where ECL is
      used for the excitation of photosensitizer instead of a physical light source to
      produce reactive oxygen species (ROS). We named this new strategy as ECL
      therapeutics. The mechanism for the ECL-therapeutics is dependent on the perfect
      spectral overlap and energy transfer from the ECL generated by luminol to
      photosensitizer, cationic oligo(p-phenylenevinylene) (OPV), to sensitize the
      surrounding oxygen molecule into ROS. Furthermore, taking into account the
      practical application of our ECL-therapeutics, we used flexible hydrogel to
      replace the liquid system to develop hydrogel antibacterial device. Because the
      chemical reaction is a slow process in the hydrogel, the luminescence could last
      for more than 10 min after only electrifying for five seconds. This unique
      persistent luminescence characteristic with long afterglow life makes them
      suitable for persistent antibacterial applications. Thus, stretchable and
      persistent hydrogel devices are designed by integrating stretchable hydrogel,
      persistent ECL and antibacterial function into hydrogel matrices. This novel
      strategy avoids the employment of external light source, making it simple,
      convenient and controllable, which exploits a new field for ECL beyond sensors
      and also opens up a new model for PDT.

PMID- 29353475
TI  - A New Lysosome-Targetable Turn-On Fluorogenic Probe for Carbon Monoxide Imaging
      in Living Cells.
AB  - A lysosome-targetable fluorogenic probe, LysoFP-NO2, was designed and synthesized
      based on a naphthalimide fluorophore that can detect selectively carbon monoxide
      (CO) in HEPES buffer (pH 7.4, 37  degrees C) through the transformation of the
      nitro group into an amino-functionalized system in the presence of CO. LysoFP-NO2
      triggered a "turn-on" fluorescence response to CO with a simultaneous increase of
      fluorescence intensity by more than 75 times. The response is selective over a
      variety of relevant reactive nitrogen, oxygen, and sulfur species. Also, the
      probe is an efficient candidate for monitoring changes in intracellular CO in
      living cells (MCF7), and the fluorescence signals specifically localize in the
      lysosome compartment.

PMID- 29353476
TI  - Hordenine: A Novel Quorum Sensing Inhibitor and Antibiofilm Agent against
      Pseudomonas aeruginosa.
AB  - The quorum sensing (QS) inhibitory activity of hordenine from sprouting barley
      against foodborne pathogen Pseudomonas aeruginosa was evaluated for the first
      time here. At concentrations ranging from 0.5 to 1.0 mg mL-1, hordenine inhibited
      the levels of acyl-homoserine lactones. The enhanced susceptibility of hordenine
      with netilmicin on P. aeruginosa PAO1 biofilm formation as well as their
      efficiency in disrupting preformed biofilms was also evaluated using scanning
      electron microscopy and confocal laser scanning microscopy (CLSM). Hordenine
      treatment inhibited the production of QS-related extracellular virulence factors
      of P. aeruginosa PAO1. Additionally, quantitative real-time polymerase chain
      reaction analysis demonstrated that the expressions of QS-related genes, lasI,
      lasR, rhlI, and rhlR, were significantly suppressed. Our results indicated that
      hordenine can serve as a competitive inhibitor for signaling molecules and act as
      a novel QS-based agent to defend against foodborne pathogens.

PMID- 29353478
TI  - Regioselective Synthesis of Indolopyrazines through a Sequential Rhodium
      Catalyzed Formal [3+3] Cycloaddition and Aromatization Reaction of
      Diazoindolinimines with Azirines.
AB  - A regioselective synthetic method for the preparation of indolopyrazines was
      demonstrated through a sequential Rh-catalyzed formal [3+3] cycloaddition and
      aromatization reaction of a wide range of diazoindolinimines with azirines.
      Because the previously reported synthetic methods afforded mixtures of
      indolopyrazines, the present method using unsymmetrical azirines has a strong
      advantage from a regioselectivity viewpoint.

PMID- 29353477
TI  - Mechanistic Insight Facilitates Discovery of a Mild and Efficient Copper
      Catalyzed Dehydration of Primary Amides to Nitriles Using Hydrosilanes.
AB  - Metal-catalyzed silylative dehydration of primary amides is an economical
      approach to the synthesis of nitriles. We report a copper-hydride(CuH)-catalyzed
      process that avoids a typically challenging 1,2-siloxane elimination step,
      thereby dramatically increasing the rate of the overall transformation relative
      to alternative metal-catalyzed systems. This new reaction proceeds at ambient
      temperature, tolerates a variety of metal-, acid-, or base-sensitive functional
      groups, and can be performed using a simple ligand, inexpensive siloxanes, and
      low catalyst loading.

PMID- 29353479
TI  - Strong Plasmonic Enhancement of a Single Peridinin-Chlorophyll a-Protein Complex
      on DNA Origami-Based Optical Antennas.
AB  - In this contribution, we fabricate hybrid constructs based on a natural light
      harvesting complex, peridinin-chlorophyll a-protein, coupled to dimer optical
      antennas self-assembled with the help of the DNA origami technique. This approach
      enables controlled positioning of individual complexes at the hotspot of the
      optical antennas based on large, colloidal gold and silver nanoparticles. Our
      approach allows us to selectively excite the different pigments present in the
      harvesting complex, reaching a fluorescence enhancement of 500-fold. This work
      expands the range of self-assembled functional hybrid constructs for harvesting
      sunlight and can be further developed for other pigment-proteins and proteins.

PMID- 29353480
TI  - Six-Component Molecular Solids: ABC[D1-(x+y)ExFy]2.
AB  - A strategy has been developed to achieve six-component molecular solids. The
      first part of the protocol involves the design and development of a family of
      stoichiometric quaternary cocrystals. It relies on the idea that when a molecule
      is in two distinct crystallographic environments in a lower-order cocrystal it
      becomes susceptible to substitution by a new molecule at the site where it is
      more weakly bound, if it is enthalpically advantageous to do so. Accordingly, a
      binary cocrystal acts as a stepping stone to a ternary, and so on. However, the
      subject system ran into a synthetic dead end at the level of quaternary
      cocrystals, in that no further crystallographic inequivalences could be found.
      This necessitated the development of the second part of the protocol, which
      exploits the shape-size similarities of 2-chloro-, 2-bromo-, and 2
      methylresorcinols (CRES, BRES, and MRES respectively) and circumvents this
      synthetic dead end to achieve several five-and six-component solids, wherein the
      fifth and sixth components are incorporated in a solid solution fashion at the
      site of the fourth component.

PMID- 29353481
TI  - Toward More Drug Like Inhibitors of Trypanosome Alternative Oxidase.
AB  - New tools are required to ensure the adequate control of the neglected tropical
      disease human African trypanosomiasis. Annual reports of infection have recently
      fallen to fewer than 5000 cases per year; however, current therapies are hard to
      administer and have safety concerns and, hence, are far from ideal. Trypanosome
      alternative oxidase is an exciting target for controlling the infection; it is
      unique to the parasite, and inhibition of this enzyme with the natural product
      ascofuranone has shown to clear in vivo infections. We report the synthesis and
      associated structure activity relationships of inhibitors based upon this natural
      product with correlation to T. b. brucei growth inhibition in an attempt to
      generate molecules that possess improved physicochemical properties and potential
      for use as new treatments for human African trypanosomiasis.

PMID- 29353482
TI  - Monitoring the Orientational Changes of Alamethicin during Incorporation into
      Bilayer Lipid Membranes.
AB  - Antimicrobial peptides (AMPs) are the first line of defense after contact of an
      infectious invader, for example, bacterium or virus, with a host and an integral
      part of the innate immune system of humans. Their broad spectrum of biological
      functions ranges from cell membrane disruption over facilitation of chemotaxis to
      interaction with membrane-bound or intracellular receptors, thus providing novel
      strategies to overcome bacterial resistances. Especially, the clarification of
      the mechanisms and dynamics of AMP incorporation into bacterial membranes is of
      high interest, and different mechanistic models are still under discussion. In
      this work, we studied the incorporation of the peptaibol alamethicin (ALM) into
      tethered bilayer lipid membranes on electrodes in combination with surface
      enhanced infrared absorption (SEIRA) spectroscopy. This approach allows
      monitoring the spontaneous and potential-induced ion channel formation of ALM in
      situ. The complex incorporation kinetics revealed a multistep mechanism that
      points to peptide-peptide interactions prior to penetrating the membrane and
      adopting the transmembrane configuration. On the basis of the anisotropy of the
      backbone amide I and II infrared absorptions determined by density functional
      theory calculations, we employed a mathematical model to evaluate ALM
      reorientations monitored by SEIRA spectroscopy. Accordingly, ALM was found to
      adopt inclination angles of ca. 69 degrees -78 degrees  and 21 degrees  in its
      interfacially adsorbed and transmembrane incorporated states, respectively. These
      orientations can be stabilized efficiently by the dipolar interaction with lipid
      head groups or by the application of a potential gradient. The presented
      potential-controlled mechanistic study suggests an N-terminal integration of ALM
      into membranes as monomers or parallel oligomers to form ion channels composed of
      parallel-oriented helices, whereas antiparallel oligomers are barred from
      intrusion.

PMID- 29353483
TI  - Molecular Insights into Glyphosate Adsorption to Goethite Gained from ATR-FTIR,
      Two-Dimensional Correlation Spectroscopy, and DFT Study.
AB  - Glyphosate (PMG) complexation on iron (hydr)oxides impacts its fate and transport
      in the environment. To decipher the molecular-level interfacial configuration and
      reaction mechanism of PMG on iron (hydr)oxides, the PMG protonation process,
      which influences the chemical and physical properties of PMG, was first
      determined using ATR-FTIR spectroscopy. The FTIR results reveal that the
      deprotonation occurs at carboxylate oxygen when pKa1< pH < pKa2, at phosphonate
      oxygen when pKa2< pH < pKa3, and at amino nitrogen when pH > pKa3. PMG
      complexation on goethite was investigated using in situ flow-cell ATR-FTIR, two
      dimensional correlation spectroscopy (2D-COS), and density functional theory
      (DFT) calculations. The results indicate that the phosphonate group on PMG
      interacts with goethite to form inner-sphere complexes with multiple
      configurations depending on pH: binuclear bidentate (BB) and mononuclear
      bidentate (MB) without proton under acidic conditions (pH 5), mononuclear
      monodentate (MM) with proton and BB without proton at pH 6-8, and MM without
      proton under alkaline conditions (pH 9). Phosphate competition significantly
      impacted the PMG adsorption capacity and its interfacial configurations. As a
      result, the stability of the adsorbed PMG was impaired, as evidenced by its
      elevated leachability. These results improve our understanding of PMG-mineral
      interactions at the molecular level and have significant implications for risk
      assessment for PMG and structural analog pollutants.

PMID- 29353484
TI  - Giant Electrostriction of Soft Nanocomposites Based on Liquid Crystalline
      Graphene.
AB  - High electromechanical coupling is critical to perform effective conversion
      between mechanical and electrical energy for various applications of
      electrostrictive polymers. Herein, a giant electrostriction effect is reported in
      liquid crystalline graphene-doped dielectric elastomers. The materials are
      formulated by a phase-transfer method which allows the solubilization of
      graphenic monolayers in nonpolar solvents. Dielectric spectroscopy is combined
      with tensile test devices to measure the true electrostriction coefficients with
      differentiating the Maxwell stress effect. Because of their liquid crystal
      structure, the resultant composites show an ultralarge electrostriction
      coefficient (~10-14 m2/V2 at 0.1 Hz) coupled with good reproducibility during
      cycles at high deformation rates. This work offers a promising pathway to design
      high-performance electrostrictive polymer composites as well as to provide
      insights into mechanisms of true electrostriction in electrically heterogeneous
      systems. The use of obtained materials as a supersensitive capacitive sensor is
      demonstrated.

PMID- 29353485
TI  - Identification and Quantification of 4-Nitrocatechol Formed from OH and NO3
      Radical-Initiated Reactions of Catechol in Air in the Presence of NOx:
      Implications for Secondary Organic Aerosol Formation from Biomass Burning.
AB  - Catechol (1,2-benzenediol) is emitted from biomass burning and produced from a
      reaction of phenol with OH radicals. It has been suggested as an important
      secondary organic aerosol (SOA) precursor, but the mechanisms of gas-phase
      oxidation and SOA formation have not been investigated in detail. In this study,
      catechol was reacted with OH and NO3 radicals in the presence of NOx in an
      environmental chamber to simulate daytime and nighttime chemistry. These
      reactions produced SOA with exceptionally high mass yields of 1.34 +/- 0.20 and
      1.50 +/- 0.20, respectively, reflecting the low volatility and high density of
      reaction products. The dominant SOA product, 4-nitrocatechol, for which an
      authentic standard is available, was identified through thermal desorption
      particle beam mass spectrometry and Fourier transform infrared spectroscopy and
      was quantified in filter samples by liquid chromatography using UV detection.
      Molar yields of 4-nitrocatechol were 0.30 +/- 0.03 and 0.91 +/- 0.06 for
      reactions with OH and NO3 radicals, and thermal desorption measurements of
      volatility indicate that it is semivolatile at typical atmospheric aerosol
      loadings, consistent with field studies that have observed it in aerosol
      particles. Formation of 4-nitrocatechol is initiated by abstraction of a phenolic
      H atom by an OH or NO3 radical to form a beta-hydroxyphenoxy/o-semiquinone
      radical, which then reacts with NO2 to form the final product.

PMID- 29353486
TI  - Assessing Mand Topography Preference When Developing a Functional Communication
      Training Intervention.
AB  - Functional communication training (FCT) is a common function-based behavioral
      intervention used to decrease problem behavior by teaching an alternative
      communication response. Therapists often arbitrarily select the topography of the
      alternative response, which may influence long-term effectiveness of the
      intervention. Assessing individual mand topography preference may increase
      treatment effectiveness and promote self-determination in the development of
      interventions. This study sought to reduce arbitrary selection of FCT mand
      topography by determining preference during response training and acquisition for
      two adults with autism who had no functional communication skills. Both
      participants demonstrated a clear preference for one mand topography during
      choice probes, and the preferred topography was then reinforced during FCT to
      reduce problem behavior and increase independent communication. The implications
      of the results for future research on mand selection during FCT are discussed.

PMID- 29353487
TI  - Absence of HIV-1 Drug Resistance Mutations Supports the Use of Dolutegravir in
      Uganda.
AB  - To screen for drug resistance and possible treatment with Dolutegravir (DTG) in
      treatment-naive patients and those experiencing virologic failure during first-,
      second-, and third-line combined antiretroviral therapy (cART) in Uganda. Samples
      from 417 patients in Uganda were analyzed for predicted drug resistance upon
      failing a first- (N = 158), second- (N = 121), or third-line [all 51 involving
      Raltegravir (RAL)] treatment regimen. HIV-1 pol gene was amplified and sequenced
      from plasma samples. Drug susceptibility was interpreted using the Stanford HIV
      database algorithm and SCUEAL was used for HIV-1 subtyping. Frequency of
      resistance to nucleoside reverse transcriptase inhibitors (NRTIs) (95%) and non
      NRTI (NNRTI, 96%) was high in first-line treatment failures. Despite lack of
      NNRTI-based treatment for years, NNRTI resistance remained stable in 55% of
      patients failing second-line or third-line treatment, and was also at 10% in
      treatment-naive Ugandans. DTG resistance (n = 366) was not observed in treatment
      naive individuals or individuals failing first- and second-line cART, and only
      found in two patients failing third-line cART, while 47% of the latter had RAL-
      and Elvitegravir-resistant HIV-1. Secondary mutations associated with DTG
      resistance were found in 2%-10% of patients failing third-line cART. Of 14 drugs
      currently available for cART in Uganda, resistance was readily observed to all
      antiretroviral drugs (except for DTG) in Ugandan patients failing first-, second
      , or even third-line treatment regimens. The high NNRTI resistance in first-line
      treatment in Uganda even among treatment-naive patients calls for the use of DTG
      to reach the UNAIDS 90:90:90 goals.

PMID- 29353488
TI  - A comparative study of the psychological problems of HIV-infected and HIV
      uninfected children in a South African sample.
AB  - According to research children living with HIV experience elevated levels of
      depression, anxiety, ADHD and disruptive behavioural disorders. Although South
      Africa's paediatric population that is infected with the human immunodeficiency
      virus (HIV) is the largest worldwide, little research has been conducted on their
      mental health challenges. However, attributing high levels of mental health
      problems solely to their HIV status can be problematic as there may be other
      contributory factors. This research explored the mental health problems of HIV
      infected children and compared these to the mental health problems of their HIV
      unaffected peers from similar backgrounds. Data was gathered from two samples of
      child and caregiver pairs. HIV-infected children (aged 6-12 years) and their
      caregivers/mothers (n = 54) were recruited from the Kalafong paediatric clinic
      where they received medical treatment and routine ART. A comparison group of 113
      HIV-uninfected children and their uninfected mothers were recruited from primary
      care clinics in the same community. Caregivers completed the Child Behaviour
      Checklist (CBCL) to assess children's mental health. Children completed the Self
      Description Questionnaire (SDQ-I) and the Revised Children's Manifest Anxiety
      Scale (RCMAS). The scores of the psychometric sub-scales of the two groups were
      compared using parametric and non-parametric statistics. HIV-infected children
      experienced more somatic and affective problems, physiological anxiety, less ADHD
      and lower self-esteem than HIV-uninfected children in the comparison group, while
      controlling for age differences. The high levels of mental health problems of
      both groups of children may be attributed to similar difficult socio-economic
      circumstances. The fact that most infected children were not aware of their HIV
      status could have influenced the results. Mental health services should not be
      limited to HIV-infected children but should form part of all health care
      services.

PMID- 29353490
TI  - The relationship between demands for lung cancer screening and the constructs of
      health belief model: a cross-sectional survey in Hefei, China.
AB  - The aim of investigation is to explore the relationship between demands for lung
      cancer screening (LCS) and the constructs derived from the health belief model
      (HBM) in Hefei. The study collected data about socio-demographics, health beliefs
      in and demands for LCS during early June to later July 2015. By constructing a
      LCS demands HBM constructs, it calculated indices of demands for LCS (DSI) and
      HBM constructs, which include perceived risk (PR) and seriousness (PS) of the
      cancers; and perceived effectiveness (PE), benefits (PB) and difficulties (PD) of
      the screening. It also performed descriptive and multivariate regression analysis
      of the demands and the HBM constructs. The amount of 823 respondents participated
      and completed the survey. 6.4% of them had ever undertaken LCS, whereas 60.1% of
      them expressed willingness to accept the service of LCS if it is free. In
      multiple regression analysis which used weights in calculating the HBM construct
      indices, education displayed significant positive associations with DSI (p =
      .044), and most of HBM constructs indices (PSI, PRI, PBI, and PDI) were
      statistically significant with DSI (p < .05). HBM-based constructs regarding LCS
      have important effects on demands for the service, and may provide effective
      paths to cancer screening promotion.

PMID- 29353489
TI  - Racial and socioeconomic disparities in the symptom reporting of persons living
      with HIV.
AB  - Persons living with HIV (PLWH) today can survive decades with the disease, making
      the symptom experience much more relevant to their lifestyle and health outcomes.
      The goal of the research reported here was to assess the symptom reporting of
      PLWH in the Unites States (US) in the combined antiretroviral therapy (cART) age
      of the epidemic. We conducted an anonymous online survey of symptomatic PLWH in
      the US and asked participants to report the frequency and intensity of 28
      frequently occurring symptoms in the past 30 days. The relationship between
      symptom reporting and demographic factors was investigated using the adaptive
      least absolute shrinkage and selection operator (LASSO) method. Fatigue was the
      most frequently reported symptom in our study population. Those with the lowest
      income were more likely to report more burdensome symptoms. In comparison to
      other racial and ethnic groups, Black non-Hispanic participants were
      significantly more likely to report a lower symptom burden score for fatigue,
      depression, muscle aches, anxiety, difficulties with memory and concentration.
      There were no racial/ ethnic differences in the burden of the symptoms related to
      sleep or neuropathy. Findings from this study present new evidence on the symptom
      reporting of PLWH in the US. Neuropathy continues to be a pervasive neurological
      symptom with no difference noted between racial/ ethnic groups.

PMID- 29353491
TI  - High-Dose Fluconazole Consolidation Therapy for Cryptococcal Meningitis in Sub
      Saharan Africa: Much to Gain, Little to Lose.
AB  - Cryptococcal meningitis accounts for an estimated 25% of AIDS-associated
      mortality in sub-Saharan Africa. Accumulating animal and human evidence suggest
      that a higher, more fungicidal, dose of fluconazole during consolidation therapy
      could be more effective in controlling residual infection and may help
      significantly reduce posthospitalization mortality. Although the potential for
      toxicity is low, the use of fluconazole at a dose of 800 mg/day during
      consolidation therapy requires examination in a randomized clinical trial. In the
      interim, within countries where postdischarge mortality from cryptococcal
      meningitis is high and amphotericin-flucytosine combination therapy remains
      unavailable, the use of high-dose fluconazole consolidation therapy deserves
      serious consideration as a strategy with limited risk and the potential for
      considerable public health benefit.

PMID- 29353492
TI  - Psychological distress in patients with chronic atrophic gastritis: the risk
      factors, protection factors, and cumulative effect.
AB  - This study aimed to examine the psychological status among Chronic Atrophic
      Gastritis (CAG) patients and to find the cumulative effects of risk and
      protective factors. A sample of 101 CAG patients completed the investigation.
      Hierarchical linear regression was used to find risk and protective factors, and
      examine the cumulative effects in risk factor index (RFI) and protective factor
      index (PFI). Results showed that nine symptoms from SCL-90-R were severer among
      CAG patients than those in adult norm. Risk factors including positive family
      history of cancer and higher negative life events could predict higher GSI (beta
      = 0.206, p = 0.023; beta = 0.398, p < 0.001; R2 = 0.203); more household
      resistant, positive coping and stronger resilience were protective factors and
      could predict GSI negatively (beta = -0.188, p = 0.020; beta = -0.350, p = 0.012;
      beta = -0.066, p = 0.621; R2 = 0.190). The GSI was positively correlated with RFI
      (beta = 0.338, p < 0.001; R2 = 0.113) and negatively related to PFI (beta = 
      0.378, p < 0.001; R2 = 0.133). In conclusion, CAG patients suffered from various
      psychological distress, and the protective factors should be enhanced
      cumulatively to protect against psychological distress.

PMID- 29353493
TI  - Exploring the Great Schism in the Social Sciences: Confirmation Bias and the
      Interpretation of Results Relating to Biological Influences on Human Behavior and
      Psychology.
AB  - The nature-nurture debate is one that biologists often dismiss as a false
      dichotomy, as all phenotypic traits are the results of complex processes of gene
      and environment interactions. However, such dismissiveness belies the ongoing
      debate that is unmistakable throughout the biological and social sciences
      concerning the role of biological influences in the development of psychological
      and behavioral traits in humans. Many have proposed that this debate is due to
      ideologically driven biases in the interpretation of results. Those favoring
      biological approaches have been accused of a greater willingness to accept
      biological explanations so as to rationalize or justify the status quo of
      inequality. Those rejecting biological approaches have been accused of an
      unwillingness to accept biological explanations so as to attribute inequalities
      solely to social and institutional factors, ultimately allowing for the
      possibility of social equality. While it is important to continue to investigate
      this topic through further research and debate, another approach is to examine
      the degree to which the allegations of bias are indeed valid. To accomplish this,
      a convenience sample of individuals with relevant postgraduate degrees was
      recruited from Mechanical Turk and social media. Participants were asked to rate
      the inferential power of different research designs and of mock results that
      varied in the degree to which they supported different ideologies. Results were
      suggestive that researchers harbor sincere differences of opinion concerning the
      inferential value of relevant research. There was no suggestion that ideological
      confirmation biases drive these differences. However, challenges associated with
      recruiting a large enough sample of experts as well as identifying believable
      mock scenarios limit the study's inferential scope.

PMID- 29353495
TI  - Neurocognitive functioning of HIV positive children attending the comprehensive
      care clinic at Kenyatta national hospital: exploring neurocognitive deficits and
      psychosocial risk factors.
AB  - Children and adolescents are affected in different ways by HIV/AIDS.
      Neurocognitive deficits are one of the most significant long term effects on HIV
      infected children and adolescents. Several factors are thought to influence
      cognitive outcomes and this include immune status, Highly Active Antiretroviral
      Therapy (HAART), education and social support. The aim of the study was to assess
      the neurocognitive function of HIV infected children and adolescents and
      correlate it with psychosocial factors. A cross sectional study was carried out
      involving a sample of 90 children living with HIV between 8 and 15 years (M =
      11.38, SD = 2.06) attending Comprehensive Care Clinic (CCC) at Kenyatta National
      Hospital (KNH). Samples were selected by using purposive sample technique.
      Kaufman Assessment Battery for Children-Second Edition was used to assess
      cognitive function and psychosocial issues were assessed using HEADS-ED. Data was
      analyzed using SPSS v23 and independent T-tests, Pearson's correlation and linear
      regression were used. The prevalence of neurocognitive deficits among HIV
      positive children attending CCC at KNH was 60% with neurocognitive performance of
      54 children being at least 2SD below the mean based on the KABC-II scores. There
      was no significant correlation between mental processing index and CD4 count
      (Pearson's rho =  -0.01, p = 0.39). There was no significant association between
      Mental Processing Index and viral load (p = 0.056) and early ARV initiation
      (0.27). Using the HEADS-ED, risks factors related to education (beta =  -5.67, p
      = 0.02) and activities and peer support (beta =  -9.1, p = 0.002) were
      significantly associated with poor neurocognitive performance. Neurocognitive
      deficits are prevalent among HIV positive children attending CCC-KNH. This extent
      of the deficits was not associated with low CD4 count, high viral load or early
      initiation in HIV care. However, poor school performance and problem with peers
      was associated with poor neurocognitive performance.

PMID- 29353494
TI  - Primary Liver Cancers, Part 2: Progression Pathways and Carcinogenesis.
AB  - Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC)
      have been increasing in incidence worldwide and are leading causes of cancer
      death. Studies of the molecular alterations leading to these carcinomas provide
      insights into the key mechanisms involved. A literature review was conducted to
      identify articles with information relevant to current understanding of the
      etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory
      diseases are the key etiological risk factors for both HCC and ICC, although
      other diseases play a role, and for many ICCs, an underlying risk factor is not
      identified. Mutations in catenin beta 1 ( CTNBB1) and tumor protein 53 (P53) are
      the main genetic alterations in HCC. Isocitrate dehydrogenases 1 and 2 (IDH1/2),
      KRAS protooncogene GTPase (KRAS), a RAS Viral Oncogene Homolog in neoroblastoma
      (NRAS) and P53 are primary genetic alterations in ICC. In both diseases, the
      mutational landscape is dependent on the underlying etiology. The most
      significant etiologies and genetic processes involved in the carcinogenesis of
      HCC and ICC are reviewed.

PMID- 29353497
TI  - [The significance of N-terminal pro-B natriuretic peptide in the management of
      adult patients with congenital heart disease - Results from the CSONGRAD
      Registry].
AB  - INTRODUCTION: The prognostic role of B-type natriuretic peptide (BNP) level was
      confirmed in chronic heart failure and congenital heart diseases irrespective of
      the aetiology. AIM: The aim of this study was to compare NT-proBNP measured in
      the clinical practice and important clinical and echocardiographic parameters in
      patients with adult congenital heart diseases under our care. METHOD: Data of a
      total of 70 patients were analysed; 34 patients had corrected tetralogy of Fallot
      and 19 patients had corrected transposition of the great arteries. In 17 further
      cases, patients with other congenital vitiums have been involved in the study. In
      all cases, out-patient examination was performed with electrocardiography,
      echocardiography and NT-proBNP measurement. The New York Heart Association (NYHA)
      stages of the patients were determined and the patients filled in a questionnaire
      regarding their quality of life. RESULTS: Elevated NT-proBNP level resulted in a
      worse quality of life (visual analogue scale, VAS) and an increased right
      ventricular end diastolic diameter; the incidence of arrhythmia increased as
      well. Negative correlation was found between the NT-proBNP level and the VAS
      value (r = -0.45, p = 0.0001) and the left ventricular ejection fraction (LV-EF)
      (r = -0.67, p = <0.0001). ROC analysis showed that NT-proBNP>=668.1 pg/ml was the
      cut-off value that most accurately predicted NYHA class III-IV (sensitivity 93%,
      specificity 63%, area under the curve 80%, p = 0.001). Similarly, NT
      proBNP>=184.7 pg/ml was found to be the cut-off value most accurately predicting
      LV-EF below 55% (sensitivity 66%, specificity 67%, area under the curve 77%, p =
      0.02). CONCLUSIONS: NT-proBNP has a role in the evaluation of adult patients with
      congenital heart diseases and in determining the prognosis of these patients, and
      in addition to other examinations used in the follow-up of these patients, NT
      proBNP may help in determining the time of reoperation or potential heart
      transplantation. Orv Hetil. 2018; 159(4): 141-148.

PMID- 29353498
TI  - [Family tree of George von Bekesy, the Nobel prized Hungarian researcher].

PMID- 29353499
TI  - [Who should decide at the end of life? International practice of advance care
      planning and possibilities for adaptation in Hungary].
AB  - At the advanced stage of serious illness, end-of-life decisions need to be made.
      Advance care planning offers patients the right to decide on their own future
      care when independent decision-making is no longer possible. The most complex and
      effective advance care plans include patients' preferred or refused medical
      treatments, care-related wishes, and individual values as well. Advance care
      planning can improve end-of-life care and contribute to higher satisfaction. It
      can also reduce distress in relatives and the costs of care. Patients'
      preferences provide a guidance for professional care. A number of studies have
      identified the benefits of advance care planning, and it has been included in
      guidelines. Potential barriers to advance care planning could be as follows:
      taboo of talking about dying, negative attitudes of patients and relatives, poor
      knowledge of professional caregivers, lack of necessary circumstances to have the
      conversation. Advance care planning is almost unknown in Hungary, although it is
      possible to refuse certain types of treatments. Cooperation of professionals,
      development of gradual and postgraduate trainings, and improvement of social
      awareness are also needed so that advance care planning can be adapted in
      Hungary. Orv Hetil. 2018; 159(4): 131-140.

PMID- 29353500
TI  - [Doege-Potter syndrome with giant malignant solitary fibrous tumour of the
      pleura].
AB  - Infrequent solitary fibrous tumours of the pleura are associated with
      hypoglycaemia only in a few percent of the cases; this condition is called Doege
      Potter syndrome, named after its first descriptors. Our 63 years old male patient
      has previously undergone clinical treatment for intrathoracic fluid accumulation
      on the left side caused by a giant tumour-like mass in the lower left lobe
      detected by CT scan. In the course of further investigations performed due to
      increasing load-induced dyspnoea, lung core biopsy verified low grade sarcoma in
      the tumour. Tumour board suggested surgery. The patient was transferred from the
      intensive care unit into the operation theater due to increasing dyspnoea and
      repeated hypoglycaemic periods in rapidly worsening general condition.
      Pneumonectomy and removal of the tumour was performed on the left side. Histology
      showed solitary fibrous tumour of the pleura corresponding to Doege-Potter
      syndrome. The patient was discharged without complications and underwent adjuvant
      chemotherapy due to pleural dissemination of the tumour observed
      intraoperatively. One year after surgery the patient underwent surgical removal
      of a locally recurrent tumour. In spite of repeated chemotherapy local and
      multiplex contralateral pulmonary progression was observed. Three-year survival
      was noted from the time of the first surgery. Orv Hetil. 2018; 159(41): 149-153.

PMID- 29353501
TI  - [Professor Bela Gomor has turned 80].

PMID- 29353503
TI  - Microwave-assisted liver resection vs. clamp crushing liver resection in
      cirrhosis patients with hepatocellular carcinoma.
AB  - PURPOSE: This study aimed to evaluate the safety and effectiveness of microwave
      ablation-assisted liver resection (MW-LR) and clamp crushing liver resection (CC
      LR) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: From July 2005 to January 2015, cirrhotic HCC patients who underwent CC
      LR (n = 191) or MW-LR (n = 112) were retrospectively analysed. We compared
      morbidity, mortality, disease-free survival (DFS) time and overall survival time
      between the CC-LR and MW-LR groups. RESULTS: The blood loss volume was
      significantly higher in the CC-LR group (mean of 752 ml) than that in the MW-LR
      group (mean of 253 ml, p < 0.001). The abdominal abscess rate was higher in the
      MW-LR group (8.9%) than that in the CC-LR group (3.1%, p = 0.029). The 30-day
      mortality rate (1.5% vs. 0.8%) and postoperative complication rate (32.9% vs.
      25.0%) were both similar between the CC-LR and MW-LR groups. MW-LR provided a
      survival benefit over CC-LR at 1, 3 and 5 years in the entire population (93.5%
      vs. 87.0%, 77.0% vs. 62.5% and 50.0% vs. 36.5%, respectively; p = 0.003). In a
      subgroup analysis, MW-LR provided a survival benefit over CC-LR for Barcelona
      Clinic Liver Cancer stage A (BCLC-A) HCC (p = 0.026) and stage B (BCLC-B) HCC (p
      = 0.035) patients and provided DFS benefits for BCLC-A HCC patients (p = 0.036).
      CONCLUSIONS: MW-LR is a safe and feasible procedure for HCC patients with a
      cirrhotic liver history.

PMID- 29353502
TI  - [The labyrinth of residual risk: reduction of the remaining lipid and
      inflammation risk in the prevention of atherosclerosis].
AB  - Since cardiovascular diseases are the main cause of mortality worldwide, the
      reduction of their risk is a crucial point of present-day medicine. It has been
      proven unequivocally that the administration of various treatments has a
      favorable effect on the frequency of cardiovascular events and on the
      atherosclerosis leading to them. Although systematic and guideline-driven
      administration of these drugs has led to a decrease in the incidence and
      mortality of vascular events, the leading position of this group of diseases in
      mortality and morbidity has not changed. That is why medicine, besides keeping up
      actual guidelines optimally, is always searching for new modalities to further
      decrease residual risk. This residual risk can be diverse. The present paper
      summarizes the possibilities of reducing residual lipid and residual inflammatory
      risk after treatment according to the guidelines. It has been proven that
      lowering LDL-cholesterol below 1.8 mmol/l has a further advantage on the
      occurrence of vascular events. Treating the elevated lipoprotein(a), triglyceride
      and low HDL-cholesterol levels should decrease the residual lipid risk. Statins
      and statin-ezetimibe combination, besides lipid modulation, have an anti
      inflammatory effect proved by C-reactive protein level reduction. Canakinumab has
      solely inflammation reducing effect through the inhibition of interleukin-1beta.
      It was administered subcutaneously once in 3 months in a large-scale clinical
      study and it has shown a 15% reduction in non-fatal myocardial infarction, non
      fatal stroke and cardiovascular death, which opens new horizons in the anti
      inflammatory treatment of atherosclerosis. Orv Hetil. 2018; 159(4): 124-130.

PMID- 29353504
TI  - Clostridium difficile control measures: current and future methods for
      prevention.
AB  - INTRODUCTION: Clostridium difficile is the most common cause of healthcare
      associated infection, and C. difficile infection (CDI) is associated with
      significant costs, morbidity, and mortality. One obstacle to preventing CDI is
      lack of high quality data on interventions to prevent CDI. This has led some to
      focus on areas, such as method of hand hygiene, unlikely to impact CDI incidence
      as much as others, such as contact precautions. In addition, existing strategies,
      although effective, do have limitations. Another challenge is the ability to
      rapidly, and accurately, diagnose CDI. Given these obstacles, new strategies to
      effectively prevent CDI are imperative to improve patient outcomes. Areas
      covered: Evidence of the interventions recommended by international scientific
      societies will be reviewed, as well as ongoing research on new strategies, such
      as screening for asymptomatic C. difficile carriage, microbiota sparing agents,
      bacteriocins and vaccines. Expert commentary: Current measures to prevent CDI are
      effective, but have significant limitations. Contact precautions and
      antimicrobial stewardship are likely the most effective of current prevention
      recommendations. Diagnostic assay utilization plays a role as well. New
      strategies to prevent CDI are needed, and, fortunately, several are being
      studied. Most likely a combination of approaches will be necessary to optimize
      CDI prevention.

PMID- 29353505
TI  - Expanded access to investigational drugs: balancing patient safety with potential
      therapeutic benefits.
AB  - INTRODUCTION: Expanded access is the use of an investigational product by
      patients with serious medical conditions without participation in a clinical
      trial. It is a complicated process involving the collaboration of many parties
      and pharmaceutical companies. Ongoing efforts focus on accelerating expanded
      access procedures in the best interest of patients with cancer. Areas covered: We
      review the regulatory and ethical challenges encountered in efforts to optimize
      expanded access. Expert opinion: In the era of personalized medicine, patients
      may benefit from novel therapeutic agents that demonstrate encouraging results in
      early studies. However, drug approval is a lengthy and cumbersome procedure that
      might exceed the time frame of a life-threatening disease. Expanded access
      provides options to patients with unmet needs. It may provide informative safety
      and efficacy data to the manufacturers and the scientific and regulatory
      organizations. Ongoing efforts are being made by global governmental and
      scientific committees, regulatory agencies, and patient organizations to address
      the ethical and regulatory issues and to optimize the expanded access process.
      Their goal is to expand access to promising novel drugs for individual patients
      and to accelerate the necessary procedures while preserving patient safety.

PMID- 29353506
TI  - Evaluation of the impact of sperm morphology on embryo aneuploidy rates in a
      donor oocyte program.
AB  - : This study investigates the correlation between sperm morphology and the
      incidence of embryo aneuploidy in an oocyte donation program. A total of 1,165
      embryos from 103 patients have been analyzed by fluorescent in situ hybridization
      (FISH) for numerical abnormalities in chromosome numbers 13, 18, 21, X, and Y.
      Data has been evaluated in five groups according to sperm morphology, which has
      been assessed according to the Kruger's strict criteria. The results did not show
      any difference in paternal (p = 0.878), maternal (p = 0.873), and donor ages (p =
      0.871), sperm counts (p = 0.782) and motility (p = 0.124), and fertilization rate
      (p = 0.080) among the groups. However, total aneuploidy rate (p < 0.001) and its
      derivatives (trisomy p = 0,042, monosomy p = 0,004) differed significantly and
      they were reversibly correlated with sperm morphology (rho correlation test;
      total aneuploidy p < 0.001, trisomy p < 0.001, monosomy p = 0.004). Therefore,
      these results suggested that diminished sperm quality is correlated to the
      aneuploidy rate in preimplantation embryos. ABBREVIATIONS: FISH: fluorescence in
      situ hybridization; ICSI: intracytoplasmic sperm injection; HCG: human chorionic
      gonadotropin.

PMID- 29353507
TI  - Increased prevalence of abnormal vertebral patterning in fetuses and neonates
      with trisomy 21.
AB  - PURPOSE: To assess the prevalence of an abnormal number of ribs in a cohort of
      fetuses and neonates with trisomy 21 and compare this with a subgroup of fetuses
      without anomalies. MATERIALS AND METHODS: Radiographs of 67 deceased fetuses,
      neonates, and infants that were diagnosed with trisomy 21 were reviewed.
      Terminations of pregnancy were included. The control group was composed of 107
      deceased fetuses, neonates, and infants without known chromosomal abnormalities,
      structural malformations, infections or placental pathology. Cases in which the
      number of thoracic ribs or presence of cervical ribs could not be reliably
      assessed were excluded. The literature concerning vertebral patterning in trisomy
      21 cases and healthy subjects was reviewed. RESULTS: Absent or rudimentary 12th
      thoracic ribs were found in 26/54 (48.1%) cases with trisomy 21 and cervical ribs
      were present in 27/47 (57.4%) cases. This prevalence was significantly higher
      compared to controls (28/100, 28.0%, Chi2(1) = 6.252, p = .012 and 28/97, 28.9%,
      Chi2(1) = 10.955, p < .001, respectively). CONCLUSIONS: Rudimentary or absent
      12th thoracic ribs and cervical ribs are significantly more prevalent in deceased
      fetuses and infants with trisomy 21.

PMID- 29353508
TI  - Vocabulary comprehension and strategies in name construction among children using
      aided communication.
AB  - Vocabulary learning reflects the language experiences of the child, both in
      typical and atypical development, although the vocabulary development of children
      who use aided communication may differ from children who use natural speech. This
      study compared the performance of children using aided communication with that of
      peers using natural speech on two measures of vocabulary knowledge: comprehension
      of graphic symbols and labeling of common objects. There were 92 participants not
      considered intellectually disabled in the aided group. The reference group
      consisted of 60 participants without known disorders. The comprehension task
      consisted of 63 items presented individually in each participant's graphic
      system, together with four colored line drawings. Participants were required to
      indicate which drawing corresponded to the symbol. In the expressive labelling
      task, 20 common objects presented in drawings had to be named. Both groups
      indicated the correct drawing for most of the items in the comprehension tasks,
      with a small advantage for the reference group. The reference group named most
      objects quickly and accurately, demonstrating that the objects were common and
      easily named. The aided language group named the majority correctly and in
      addition used a variety of naming strategies; they required more time than the
      reference group. The results give insights into lexical processing in aided
      communication and may have implications for aided language intervention.

PMID- 29353509
TI  - Epidemiology of tattoo skin disease in captive common bottlenose dolphins
      (Tursiops truncatus): Are males more vulnerable than females?
AB  - Clinical and epidemiological features of tattoo skin disease (TSD) are reported
      for 257 common bottlenose dolphins held in 31 facilities in the Northern
      Hemisphere. Photographs and biological data of 146 females and 111 males were
      analyzed. Dolphins were classified into three age classes: 0-3 years, 4-8 years,
      and older than 9 years. From 2012 to 2014, 20.6% of the 257 dolphins showed
      clinical TSD. The youngest dolphins with tattoo lesions were 14 and 15 months
      old. TSD persisted from 4 to 65 months in 30 dolphins. Prevalence varied between
      facilities from 5.6% to 60%, possibly reflecting variation in environmental
      factors. Unlike in free-ranging Delphinidae, TSD prevalence was significantly
      higher in males (31.5%) than in females (12.3%). Infection was age-dependent only
      in females. Prevalence of very large tattoos was also higher in males (28.6%)
      than in females (11.1%). These data suggest that male T. truncatus are more
      vulnerable to TSD than females, possibly because of differences in immune
      response and susceptibility to captivity-related stress.

PMID- 29353510
TI  - Effects of passive smoking on lung function tests in preschool children born late
      preterm: a preventable health priority.
AB  - OBJECTIVE: Late-preterm delivery is known to be associated with potential adverse
      effects on lung development. Passive smoking may result in alterations of
      pulmonary function in infants born late-preterm. Impulse oscillometry (IOS) is a
      noninvasive, rapid, and practicable technique that can assess lung function. This
      study aimed to evaluate the effect of passive smoking on lung function tests in
      preschool children born late-preterm using IOS. METHODS: The study population
      consisted of a total of 139 children between 3 and 7 years of age born late
      preterm who were being followed-up at our outpatient unit at the time of study
      period. Late-preterms were subcategorized according to presence or absence of
      exposure to passive smoking (PS). Those with and without exposure to passive
      smoking were referred to as PS group (56.1%, n = 78) and non-PS group (43.9%, n =
      61), respectively. Resistance (R5-R20), reactance (X5-X20), and resonant
      frequency were measured by impulse oscillometry (IOS) at 5-20 Hz. RESULTS: Median
      R5-R20 and Z5 were significantly higher and median X10 was significantly lower in
      PS group compared to non-PS group (p < .05). CONCLUSIONS: This study demonstrated
      that passive smoking significantly increases peripheral airway resistance and
      seems to adversely affect lung function in children born late-preterm.

PMID- 29353511
TI  - Identified mental disorders in older adults in primary care: A cross-sectional
      database study.
AB  - INTRODUCTION: Identifying and managing mental disorders among older adults is an
      important challenge for primary care in Europe. Electronic medical records (EMRs)
      offer considerable potential in this regard, although there is a paucity of data
      on their use for this purpose. OBJECTIVES: To examine the prevalence/treatment of
      identified mental disorders among older adults (over 55 years) by using data
      derived from EMRs in general practice. METHODS: We utilized data from a cross
      sectional study of mental disorders in primary care, which identified patients
      with mental disorders based on diagnostic coding and prescribed medicines. We
      collected anonymized data from 35 practices nationally from June 2014 to March
      2015, and secondary analysis of this dataset examined the prevalence of mental
      disorders in adults aged over 55 years. RESULTS: 74,261 patients aged over 55
      years were identified, of whom 14,143 had a mental health disorder (prevalence
      rate of 19.1%). There was considerable variation between practices (range: 3.7
      38.9%), with a median prevalence of 23.1%. Prevalence increased with age, from
      14.8% at 55-59 years to 28.9% at 80-84 years. Most common disorders were
      depression (17.1%), panic/anxiety (11.3%), cognitive (5.6%), alcohol (3.8%) and
      substance use (3.8%). CONCLUSIONS: Examining mental disorders among older adults
      using data derived from EMRs is feasible. Mental disorders are common among older
      adults attending primary care and this study demonstrates the utility of
      electronic medical records in epidemiological studies of large populations in
      primary care.

PMID- 29353512
TI  - Social Disadvantage, Severe Child Abuse, and Biological Profiles in Adulthood.
AB  - Guided by the stress process model and the life course perspective, we
      hypothesize: (1) that childhood abuse is concentrated, in terms of type and
      intensity, among socially disadvantaged individuals, and (2) that experiencing
      serious abuse contributes to poor biological profiles in multiple body systems in
      adulthood. Data came from the Biomarker subsample of Midlife in the United States
      (2004-2006). We used latent class analysis to identify distinct profiles of
      childhood abuse, each reflecting a combination of type and severity. Results
      indicate that disadvantaged groups, women, and those from disadvantaged families
      are at greater risk of experiencing more severe and multiple types of abuse.
      Those with more severe and multifaceted childhood abuse show greater
      physiological dysregulation. Childhood abuse experiences partially accounted for
      the social status differences in physiological profiles. Our findings underscore
      that differential exposure to serious childhood stressors plays a significant
      role in gender and class inequalities in adult health.

PMID- 29353514
TI  - Correction to: Vanukuru J, et al., A clinical and microbiological study of
      puerperal sepsis in a tertiary care hospital in India.

PMID- 29353513
TI  - Effects of different open cryo-carriers on embryo survival and clinical outcome
      in frozen embryo transfer cycle patients.
AB  - : The purpose of this study was to compare the efficacy of different open cryo
      carriers: the CryoloopTM, CryotopTM, and CryoleafTM, in embryo survival and
      clinical outcome in patients with frozen embryo transfer (FET) cycle. We analyzed
      the embryo survival rate and clinical outcome in 325 patients of 348 FET cycles
      vitrified with the CryoloopTM (160 cycles), CryotopTM (105 cycles), or CryoleafTM
      (83 cycles). No significant differences were observed in embryo survival rate
      (98.8% vs. 100% vs. 97.7%, p > 0.05), HCG positive rate (58.8% vs. 63.8% vs.
      57.8%, p > 0.05), biochemical pregnancy rate (6.9% vs. 11.4% vs. 9.6%, p > 0.05),
      or implantation rate (33.2% vs. 37.4% vs. 34.1%, p > 0.05) in the three groups
      respectively. The early abortion rate of the CryoloopTM group was significantly
      higher than that of the CryotopTM and CryoleafTM group (27.1% vs. 3.6% and 7.5%,
      p < 0.05). At the same time, the average female age of the CryoloopTM group was
      significantly older by 1 year than that of the CryotopTM and CryoleafTM group
      (33.29 +/- 4.71 years vs. 31.96 +/- 4.27 years and 31.1 +/- 4.28 years, p <
      0.05). There was no significant difference in take home baby rate (38.1% vs.
      46.7% vs. 43.4, p > 0.05) or birth weight among the groups (2893.5 +/- 780.8 g
      vs. 2778.4 +/- 710.0 g vs. 2724.5 +/- 838.8 g, p > 0.05). No case of neonatal
      malformation was observed in the present study. Overall, CryotopTM and CryoleafTM
      were effective for embryo vitrification at both the cleavage and blastocyst stage
      according to the results of clinical outcome and infant characteristics. However,
      CryoloopTM led to a decreased positive HCG rate and increased early abortion
      rate, heightened at the cleavage stage. ABBREVIATIONS: LN2: liquid nitrogen; CPA:
      cryoprotectant; ART: assisted reproductive technology; IVF: in vitro
      fertilization; ICSI: intracytoplasmic sperm injection; BMI: body mass index; FSH:
      follicular stimulation hormone; COH: controlled ovarian hyperstimulation; FET:
      frozen embryo transfer; mm: millimeter; HCG: human chorionic gonadotropin; RCT:
      randomized clinical trial; NC: natural cycle; AC: artificial cycle; EM:
      equilibration medium; DMSO: dimethyl sulphoxide; EG: ethylene glycol; VM:
      vitrification medium; WM: warming medium.

PMID- 29353515
TI  - Use of a Non-Crosslinked Porcine Dermal Matrix in Repair of the Achilles and
      Other Tendons of the Foot.
AB  - BACKGROUND: Ankle tendon augmentation with biological matrixes has been shown to
      be beneficial, especially for Achilles tendon rupture as it adds to the integrity
      of the repair. Biologic matrix augmentation has been used increasingly in chronic
      and complex injuries where reinforcement is required. The objective of this study
      was to present outcomes of a series of patients who underwent tendon repair
      augmented with a new biologic matrix. METHODS: Sixteen patients underwent ankle
      tendon repair, augmented with Proformix biologic tissue matrix. Patients were
      evaluated pre- and postoperatively for function and pain, and were followed for
      up to 3 years for complications. RESULTS: This study included 10 females and 6
      males, with a mean age of 44.6 years (range, 23-71 years). Patients were
      evaluated at 2 months postoperatively, and then further followed for a mean 19.0
      months (range 7-38 months) to assess complications and reinjuries. Foot and Ankle
      Disability Index scores significantly increased from preoperatively (38.3) to 2
      months postoperatively (85.2) ( P < .001). Furthermore, there were no reports of
      reruptures or significant complications. CONCLUSIONS: Weakness or rupture in
      tendons of the foot, especially the Achilles tendon, can be treated surgically
      and the repair augmented with Proformix, a new, biological matrix. Our study
      presented a series of 16 patients whose surgical repairs had been augmented with
      the new biological matrix, all of whom have achieved excellent results. LEVELS OF
      EVIDENCE: Level IV: Case series.

PMID- 29353517
TI  - Visual-spatial cognition in children using aided communication.
AB  - Children with severe motor impairments are restricted in their manipulation and
      exploration of objects, but little is known about how such limitations influence
      cognitive development. This study investigated visual-constructional abilities in
      75 children and adolescents, aged 5;0-15;11 (years;months), with severe speech
      impairments and no intellectual disabilities (aided group) and in 56 children and
      adolescents with typical development (reference group). Verbal comprehension, non
      verbal reasoning, and visual-spatial perception were assessed with standardized
      tests. The task of the participants was to verbally instruct communication
      partners to make physical constructions identical to models that the partner
      could not see. In the aided group, 55.7% of the constructions were identical to
      the models participants described, compared to 91.3% in the reference group. In
      the aided group, test results explained 51.4% of the variance in construction
      errors. The results indicate that the participants' language skills were decisive
      for construction success. Visual-perceptual challenges were common among the
      aided communicators, and their instructions included little information about
      size and spatial relations. This may reflect less experience with object
      manipulation and construction than children with typical development, and using
      aided communication to instruct others to make three-dimensional constructions.
      The results imply a need for interventions that compensate for the lack of
      relevant experience.

PMID- 29353518
TI  - Accuracy and repeatability of the Dopplex Ability.
AB  - BACKGROUND: Ankle-brachial index (ABI) and pulse volume recordings (PVR) are non
      invasive tests used in diagnosis of peripheral arterial disease (PAD). The
      Dopplex Ability is an automated ABI/PVR device utilising air plethysmography,
      offering easy and rapid PAD diagnosis. The accuracy and repeatability of the
      Dopplex were assessed in comparison to the Doppler/air plethysmography-based
      Parks Flo-Lab system. METHODS: Sixty-six patients (n = 129 lower limbs) were
      assessed with both Dopplex and Parks systems. For Dopplex ABI and PVR to be
      deemed accurate, it had to be within +/-10% of the Parks ABI, and the PVR grade
      (1-4) had to be equal. The coefficient of variation (CV) was calculated from
      three repeat ABI/PVR readings to assess repeatability. RESULTS: The Dopplex and
      Parks devices correlated poorly for ABI (R2 = 0.17) with only 43% of ABIs and 69%
      of PVRs meeting the accuracy criteria compared to the Parks values. The
      specificity and sensitivity were 56% and 82%, respectively for ABI, and 91% and
      89%, respectively for PVRs. The Dopplex showed a significantly higher CV for both
      ABIs and PVRs compared to the Parks. CONCLUSION: We found the Dopplex device to
      demonstrate suboptimal accuracy and repeatability in assessing ABI/PVR, and it
      was deemed unsuitable for use in our community.

PMID- 29353516
TI  - Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the
      therapy's history, efficacy and application in humans.
AB  - Hyperthermia therapy (HT) is the exposure of a region of the body to elevated
      temperatures to achieve a therapeutic effect. HT anticancer properties and its
      potential as a cancer treatment have been studied for decades. Techniques used to
      achieve a localised hyperthermic effect include radiofrequency, ultrasound,
      microwave, laser and magnetic nanoparticles (MNPs). The use of MNPs for
      therapeutic hyperthermia generation is known as magnetic hyperthermia therapy
      (MHT) and was first attempted as a cancer therapy in 1957. However, despite more
      recent advancements, MHT has still not become part of the standard of care for
      cancer treatment. Certain challenges, such as accurate thermometry within the
      tumour mass and precise tumour heating, preclude its widespread application as a
      treatment modality for cancer. MHT is especially attractive for the treatment of
      glioblastoma (GBM), the most common and aggressive primary brain cancer in
      adults, which has no cure. In this review, the application of MHT as a
      therapeutic modality for GBM will be discussed. Its therapeutic efficacy,
      technical details, and major experimental and clinical findings will be reviewed
      and analysed. Finally, current limitations, areas of improvement, and future
      directions will be discussed in depth.

PMID- 29353519
TI  - Extracellular vesicles from parasitic helminths and their potential utility as
      vaccines.
AB  - INTRODUCTION: Helminths are multicellular parasites affecting nearly three
      billion people worldwide. To orchestrate a parasitic existence, helminths secrete
      different molecules, either in soluble form or contained within extracellular
      vesicles (EVs). EVs are secreted by most cell types and organisms, and have
      varied roles in intercellular communication, including immune modulation and
      pathogenesis. Areas covered: In this review, we describe the nucleic acid and
      proteomic composition of EVs from helminths, with a focus on the protein vaccine
      candidates present on the EV surface membrane, and discuss the potential utility
      of helminth EVs and their constituent proteins in the fight against helminth
      infections. Expert commentary: A significant number of proteins present in
      helminth-secreted EVs are known vaccine candidates. The characterization of
      helminth EV proteomes will shed light on host-pathogen interactions, facilitate
      the discovery of new diagnostic biomarkers, and provide a novel approach for the
      development of new control measures against helminth infections.

PMID- 29353520
TI  - Indications, complications, and outcomes following surgical management of locally
      advanced and metastatic renal cell carcinoma.
AB  - INTRODUCTION: Surgery may set the basis for a potential cure or would provide the
      best achievable quality of life in locally advanced or metastatic renal cell
      carcinoma (mRCC). However, survival extension with this approach would be scarce
      and not exempt from adverse events, thus preventing its recommendation in an
      already frail patient. An evidence based analysis on the role of surgery in each
      of the possible clinical scenarios involved under this heading may provide a
      clear picture on this issue and would be of value in the decision making process.
      Areas covered: Current literature was queried in PubMed/Medline in a systematic
      fashion. Manuscripts included were selected according to the quality of the data
      provided. A narrative review strategy was adopted to summarize the evidence
      acquired. Expert commentary: A surgery-based multimodal treatment approach should
      be strongly considered after adequate counseling in locally advanced and mRCC,
      since it may provide for additional benefits in terms of survival. However, a
      critical reevaluation of its adequacy, optimal timing, and selection of ideal
      candidates is currently ongoing.

PMID- 29353521
TI  - Antiangiogenic evaluation of ZnWO4 nanoparticles synthesised through microwave
      assisted hydrothermal method.
AB  - Angiogenesis, the complex process of formation of new blood vessels from pre
      existing blood vessels, which involves the participation of several pro- and anti
      angiogenic factors, is implicated in many physiological and pathological
      conditions. Nanoparticle-based anti-angiogenic activity at the tumour tissue,
      harnessed by the Enhanced Permeability and Retention Effect (EPR effect), could
      potentially become a breakthrough therapy to halt tumour progression. Herein, we
      evaluate the anti-angiogenic effect of ZnWO4 nanoparticles (NPs). The
      nanoparticles were obtained by microwave-assisted hydrothermal synthesis (MAHS)
      at 120  degrees C for 60 min and were structurally characterised by X-ray
      diffraction (XRD) and micro-Raman (MR) spectroscopy. The mean size and
      polydispersity index were estimated by Zeta potential analysis. The XRD analysis
      revealed structural organisation at a long-range order, with an average
      crystallite size of around 3.67 nm, while MR revealed short-range order for
      ZnWO4. The anti-angiogenic potential of zinc tungstate nanoparticles was
      investigated through the chorioallantoic membrane assay (CAM) using fertilised
      chicken eggs. We demonstrate, in an unprecedented way, that nanocrystalline ZnWO4
      NPs obtained by MAHS, at low reaction temperatures, showed excellent anti
      angiogenic properties even at low concentrations. The ZnWO4 NPs were further
      evaluated for its cytotoxicity in vitro.

PMID- 29353522
TI  - Expanding the malaria molecular diagnostic options: opportunities and challenges
      for loop-mediated isothermal amplification tests for malaria control and
      elimination.
AB  - INTRODUCTION: The loop-mediated isothermal amplification (LAMP) technique holds
      substantial promise as an alternative easy-to-use molecular test for malaria
      parasite detection. Several modifications to the initial malaria LAMP assay have
      been made in an effort to make the LAMP platform more field-friendly. Areas
      covered: A PubMed literature search was performed using the following search
      terms: 'malaria,' 'loop mediated isothermal amplification', 'LAMP', 'molecular
      tests' and 'diagnostics'. The authors review the currently reported malaria LAMP
      assays and discuss what requirements would be needed to make malaria LAMP assays
      field-usable, especially in the context of malaria elimination. Expert
      commentary: Expanding the malaria LAMP tests as options for use in malaria
      control programs will require addressing some important challenges such as the
      need for simplified sample preparation steps; ready to use kits that require no
      cold chain; the use of a non-subjective results readout and preferably cost
      effectiveness. Two malaria LAMP kits are now CE-marked and commercially
      available: the Loopamp MALARIA kit and the Illumigene malaria LAMP. Malaria LAMP
      tests, like other molecular tests, will likely be utilized in very specific
      studies such as: to evaluate 'detect and treat' strategies; in controlled malaria
      infection trials or drug efficacy trials and as confirmatory test in reference
      laboratories.

PMID- 29353523
TI  - Acromioclavicular joint disruptions: A comparison of two surgical approaches
      'hook' and 'rope'.
AB  - INTRODUCTION: Acromioclavicular joint injuries are common shoulder girdle
      injuries most commonly resulting from a direct blow to the acromion with the arm
      adducted. Type-I or type-II acromioclavicular joint injuries can be managed with
      sling immobilization, early shoulder motion, and physiotherapy. The management of
      type-III injuries remains controversial and is individualized. Type IV and V
      injuries should be treated surgically. A myriad of surgical techniques for the
      management of acromioclavicular joint injuries have been reported. METHODS: We
      present a comparative study of 76 patients treated with two most common
      modalities of treatment for AC joint disruption and that is Hook plate
      stabilisation (n=52) or arthroscopically assisted tight rope stabilisation
      (n=24). The primary objective was to establish whether hook plate stabilization
      was superior compared to arthroscopic tight rope fixation in reducing pain and
      increasing function in the short-term and long-term for patients with AC joint
      disruptions III-IV. We also wanted to assess how quickly patients returned to
      their work/job. It was a prospective study, we included all the patients operated
      between 2008 and 2015 for AC joint disruption by the two shoulder surgeons of our
      department. All patients followed a strict physiotherapy protocol and were
      assessed at 6 weeks, 3 months and 12 months. We used the Harm and cost criteria
      of assessment and the patient specific functional outcome scores. RESULTS: Both
      modalities of treatment have high patient satisfaction rate, return to work is
      faster in tight rope group but after a year both group of patients returned to
      their premorbid state. Removal of hook plate is not mandatory and lysis of
      acromion is rare (1% in our series). CONCLUSION: Despite the fact that both
      methods yielded similar results and have statistically similar number of
      complications, the type of postoperative complications was different between
      groups. The plate group had more postoperative pain and worse function but both
      aspects improved after plate removal. The rope group had more complex
      complications including deep infection and recurrence of deformity and fracture.
      These differences should be taken into consideration when consenting the patient
      regarding possible treatment.

PMID- 29353525
TI  - Reflections on a year of transition.

PMID- 29353524
TI  - Violence breeds violence: burnout as a mediator between patient violence and
      nurse violence.
AB  - The present study examines whether patient-perpetrated violence triggers anger,
      hatred and other negative emotions that, under certain circumstances, might
      motivate nurses to behave violently with patients. In doing so, this study
      considers burnout as a mediator in the patient violence-nurse violence
      relationship. To test the causal paths, data were collected from 182 nurses
      working in two government-sector teaching hospitals of Pakistan's Punjab
      province. Results confirm that patient violence toward nurses leads to nurse
      violence toward patients through the mediating effect of burnout. The study
      advises hospitals to provide wellness and stress management programs to nurses
      who regularly experience events involving patient violence. Hospitals may
      consider allowing nurses to take short breaks after an encounter with violently
      behaving patients. In addition, hospitals should conduct empathy-promoting
      training, emotional intelligence training and 'lens of the patient' training
      programs to sensitize their nursing staff.

PMID- 29353526
TI  - Using 3-Dimensional Modeling to Customize Titanium Plates for Repair of Chest
      Wall Trauma.
AB  - BACKGROUND: Open reduction and internal fixation of rib fractures is recommended
      to decrease mortality, shorten the duration of mechanical ventilation, and lower
      hospital length of stay. Prosthetic titanium plates are frequently used to repair
      chest wall trauma, and are typically contoured to the patient's anatomy at the
      time of implant in the operating room. We describe the use of 3-dimensional (3D)
      digitally corrected rapid prototyping to generate a model of a patient's skeletal
      anatomy for the purposes of preoperative customization of standard titanium
      plates for fixation of rib fractures. METHODS: A computed tomography imaging
      Digital Imaging and Communication in Medicine data set was segmented. Rib
      fractures were virtually realigned using the mirrored normal anatomy as a guide.
      The model was printed and used to customize titanium rib fixation plates prior to
      the procedure. RESULTS: Preoperative shaping of 5 titanium plates using the final
      3D model required a total of 5.65 minutes. Surgical fixation of 4 of the
      patient's 5 fractures was accomplished using the titanium plates that were
      preoperatively shaped using our 3D model. DISCUSSION: We demonstrate successful
      use of a digitally rendered model to preoperatively customize standard titanium
      rib fixation plates. Compared with intraoperative contouring of rib fixation
      plates, we believe that this approach facilitates repair of complex rib
      fractures, saving time in the operating room. We believe this technique can
      improve the accuracy of reductions, increase the ease and efficiency of these
      procedures, and afford benefits in reducing surgical stress on patients who have
      already suffered significant trauma.

PMID- 29353528
TI  - The Theory of Dyadic Illness Management.
AB  - Despite the importance of both members of the adult patient-care partner dyad, a
      majority of research on illness management is focused on the patient or the care
      partner. The basic principle of the Theory of Dyadic Illness Management is that
      illness management is a dyadic phenomenon; the theory focuses extensively on the
      dyad as an interdependent team. The way dyads appraise illness as a unit
      influences the ways in which they engage in behaviors to manage illness together
      in a recursive fashion that influences dyadic health. Optimizing the health of
      both members of the dyad is a goal of the theory. In turn, the health of the dyad
      can feedback to influence how they appraise and manage illness together. Finally,
      dyadic illness management is an inherently variable process that is influenced by
      several contextual factors. Supportive evidence and implications for practice and
      future research are presented.

PMID- 29353527
TI  - Irrigation Versus Suction Alone in Laparoscopic Appendectomy: Is Dilution the
      Solution to Pollution? A Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To investigate outcomes of peritoneal irrigation versus suction
      without irrigation in patients undergoing emergency laparoscopic appendectomy.
      METHODS: We performed a systematic review and conducted a search of electronic
      information sources to identify all randomized controlled trials (RCTs) and
      observational studies investigating outcomes of irrigation versus suction alone
      in patients undergoing emergency laparoscopic appendectomy. We used the Cochrane
      risk of bias tool and the Newcastle-Ottawa scale to assess the risk of bias of
      RCTs and observational studies, respectively. Random-effects models were applied
      to calculate pooled outcome data. RESULTS: We identified 3 RCTs and 2
      retrospective observational studies, enrolling 2511 patients. Our results
      suggested that there was no difference between peritoneal irrigation and suction
      alone in terms of intraabdominal abscess rate (odds ratio = 2.39, 95% confidence
      interval [CI] = 0.49-11.74, P = .28), wound infection (risk difference = 0.00,
      95% CI = -0.04 to 0.05, P = .85), and length of stay (mean difference = -1.02,
      95% CI = -3.10 to 1.07, P = .34); however, peritoneal irrigation was associated
      with longer operative time (mean difference = 7.12, 95% CI = 4.33 to 9.92, P <
      .00001). Our results remained consistent when randomized trials, adult patients,
      and pediatric patients were analyzed separately. CONCLUSIONS: The best available
      evidence suggests that the peritoneal irrigation with normal saline during
      laparoscopic appendectomy does not provide additional benefits compared with
      suction alone in terms of intraabdominal abscess, wound infection, and length of
      stay but it may prolong the operative time. The quality of the best available
      evidence is moderate; therefore, high-quality RCTs, which are adequately powered,
      are required to provide more robust basis for definite conclusions.

PMID- 29353529
TI  - Ultrasound Shear Wave Elastography of the Normal Prostate: Interobserver
      Reproducibility and Comparison with Functional Magnetic Resonance Tissue
      Characteristics.
AB  - The purpose of this study was to establish interobserver reproducibility of
      Young's modulus (YM) derived from ultrasound shear wave elastography (US-SWE) in
      the normal prostate and correlate it with multiparametric magnetic resonance
      imaging (mpMRI) tissue characteristics. Twenty men being screened for prostate
      cancer underwent same-day US-SWE (10 done by two blinded, newly-trained
      observers) and mpMRI followed by 12-core biopsy. Bland-Altman plots established
      limits of agreement for YM. Quantitative data from the peripheral zone (PZ) and
      the transitional zone (TZ) for YM, apparent diffusion coefficient (ADC, mm2/s
      from diffusion-weighted MRI), and Ktrans (volume transfer coefficient, min-1), Ve
      (extravascular-extracellular space, %), Kep (rate constant, /min), and initial
      area under the gadolinium concentration curve (IAUGC60, mmol/L/s) from dynamic
      contrast-enhanced MRI were obtained for slice-matched prostate sextants.
      Interobserver intraclass correlation coefficients were fair to good for
      individual regions (PZ = 0.57, TZ = 0.65) and for whole gland 0.67, (increasing
      to 0.81 when corrected for systematic observer bias). In the PZ, there were weak
      negative correlations between YM and ADC ( p = 0.008), and Ve ( p = 0.01) and a
      weak positive correlation with Kep ( p = 0.003). No significant intermodality
      correlations were seen in the TZ. Transrectal prostate US-SWE done without
      controlling manually applied probe pressure has fair/good interobserver
      reproducibility in inexperienced observers with potential to improve this to
      excellent by standardization of probe contact pressure. Within the PZ, increase
      in tissue stiffness is associated with reduced extracellular water (decreased
      ADC) and space (reduced Ve).

PMID- 29353530
TI  - Understanding how Afghan women utilise a gender transformative and economic
      empowerment intervention: A qualitative study.
AB  - The processes through which women's economic empowerment interventions are
      envisaged to improve women's health are strongly embedded in notions of building
      women's agency and autonomy. Yet despite the ubiquity of such interventions,
      there remains incredibly little qualitative work exploring how women actually
      utilise interventions to reshape their lives and wellbeing. Drawing on 9 focus
      groups discussions among 52 women who participated in the Women for Women
      International intervention in Afghanistan, an economic strengthening and social
      empowerment intervention, we explore processes of change. Data showed women
      learnt new skills around numeracy and animal husbandry; they perceived themselves
      to have become more respected within the household setting; they invested cash
      they received for intervention attendance in businesses, primarily their
      husband's or family's, and saved cash. Women did not, however, report their
      relationships to have been radically restructured. Rather women described
      incremental changes in their relationships within their household and used what
      they gained from the intervention to secure and sustain this. This
      conceptualisation of agency and empowerment reflects approaches to understanding
      agency, which move away from 'action-oriented' understandings, to ones that
      recognise 'distributed agency' as pathways to change through interventions.

PMID- 29353531
TI  - Oxytocin receptor gene variation, behavioural inhibition, and adult separation
      anxiety: Role in complicated grief.
AB  - OBJECTIVES: Complicated grief (CG) following bereavement significantly increases
      the risk for mood and anxiety disorders. The severity of grief reactions may be
      interactively influenced by temperamental and psychological factors such as
      behavioural inhibition (BI) and separation anxiety (SA) as well as biological
      factors. Given its central role in attachment and stress processing, a genetic
      variant in the oxytocin receptor (OXTR) gene was thus investigated in order to
      elucidate the direction of association as well as its interaction with BI and SA
      in the moderation of CG severity. METHODS: Ninety-three patients with mood and
      anxiety disorders were evaluated for CG by means of the Inventory of Complicated
      Grief (ICG), for BI using the Retrospective Self-Report of Inhibition (RSRI), and
      for symptoms of SA during adulthood using the Adult Separation Anxiety Scale (ASA
      27). All patients were genotyped for OXTR rs2254298. RESULTS: OXTR genotype
      interacted with BI and, on a trend-level, with adult SA, to increase CG.
      Specifically, higher levels on the RSRI and ASA-27 scales, respectively, were
      related to higher ICG scores in GG genotype carriers. CONCLUSIONS: The present
      study for the first time suggests a gene-environment interaction effect of an
      OXTR gene variant with BI and possibly also symptoms of adult SA in the
      moderation of vulnerability for CG.

PMID- 29353533
TI  - Recognition of emotional facial expressions in benzodiazepine dependence and
      detoxification.
AB  - INTRODUCTION: The study investigates how benzodiazepine (BZD) use and
      detoxification affects empathy and the recognition and intensity rating of
      emotional facial expressions. The sample comprised 43 participants in three
      groups: (1) during detoxification (N = 13), (2) after detoxification (N = 15),
      (3) a matched control group (N = 15). Clinical subjects were recruited from in
      patients of an addiction treatment unit. METHODS: Empathy levels were tested with
      the Empathy Quotient (EQ-Short). Recognition accuracy and emotion intensity
      rating were based on a computerised task displaying static and dynamic facial
      expressions of joy, anger, sadness, and fear. RESULTS: The controls proved more
      accurate than both experimental groups in identifying facial expressions of
      negative emotions. Joy recognition proved most accurate overall. Among the
      clinical subjects, women in particular exhibited an impaired ability to correctly
      identify negative emotions from facial expressions. Dynamic stimuli were better
      recognised than static ones albeit only in the experimental groups. No
      significant differences were found for emotion intensity ratings and EQ scores.
      CONCLUSION: Our findings suggest that the impaired facial emotion recognition
      accuracy is not caused by deficits in empathy. No improvement was recorded post
      detoxification which may indicate impaired interpersonal functioning among BZD
      users. Further research is warranted in light of this study's limitations.

PMID- 29353532
TI  - Live Quantitative Monitoring of Mineral Deposition in Stem Cells Using
      Tetracycline Hydrochloride.
AB  - The final stage of in vitro osteogenic differentiation is characterized by the
      production of mineral deposits containing calcium cations and inorganic
      phosphates, which populate the extracellular matrix (ECM) surrounding the cell
      monolayer. Conventional histological techniques for the assessment of
      mineralization, such as Von Kossa and Alizarin Red S staining, are end point
      techniques requiring cell fixation. Moreover, in both cases staining quantitation
      requires dye extraction, which irreversibly alters the ECM conformation and
      structure, therefore preventing the use of the sample for further analysis. In
      this study, the use of tetracycline hydrochloride (TC) is proposed for the
      nondestructive staining, quantitation, and imaging of mineralizing bone-like
      nodules in live cultures of human bone marrow mesenchymal stem cells cultured
      under osteogenic conditions. Overnight administration of TC to living cells was
      shown not to alter the metabolic activity or the progression of cell
      differentiation. When applied to differentiating cultures, cell exposure to
      serial doses of TC was found to produce quantifiable fluorescence emission
      specifically in osteogenic cultures. Incubation with TC enabled fluorescence
      imaging of mineralized areas in live cultures and the combination with other
      fluorophores using appropriate filters. These results demonstrate that serial TC
      administration over the differentiation time course provides a qualitative and
      quantitative tool for the monitoring and evaluation of the differentiation
      process in live cells.

PMID- 29353534
TI  - No detectable effects of acute tryptophan depletion on short-term immune system
      cytokine levels in healthy adults.
AB  - OBJECTIVES: Recent research suggested an influence of diminished central nervous
      serotonin (5-HT) synthesis on the leptin axis via immunological mechanisms in
      healthy adult females. However, studies assessing immunological parameters in
      combination with dietary challenge techniques that impact brain 5-HT synthesis in
      humans are lacking.  Methods: In the present trial, a pilot analysis was
      conducted on data obtained in healthy adult humans receiving either different
      dietary acute tryptophan depletion (ATD) challenge or tryptophan (TRP)-balanced
      control conditions (BAL) to study the effects of reduced central nervous 5-HT
      synthesis on serum tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL
      1beta) and IL-6 concentrations. The data of N = 35 healthy adults were analysed
      who were randomly subjected to one of the following two dietary conditions in a
      double-blind between-subject approach: (1) The Moja-De ATD challenge (ATD), or
      (2) TRP-balanced control condition for ATD Moja-De (BAL). Serum concentrations
      for the assessment of relevant parameters (TNF-alpha, IL-1beta and IL-6) and
      relevant TRP-related characteristics after the respective challenge procedures
      were assessed at baseline (T0) and in hourly intervals after administration over
      a period of 6 h (T1-T6).  Results: The ATD condition did not result in
      significant changes to cytokine concentrations for the entire study sample, or in
      male and female subgroups. Depletion of CNS 5-HT via dietary TRP depletion
      appears to have no statistically significant short-term impact on cytokine
      concentrations in healthy adults.  Conclusions: Future research on immunological
      stressors in combination with challenge techniques will be of value in order to
      further disentangle the complex interplay between brain 5-HT synthesis and
      immunological pathways.

PMID- 29353535
TI  - Eating behavior traits of successful weight losers during 12 months of alternate
      day fasting: An exploratory analysis of a randomized controlled trial.
AB  - BACKGROUND: Alternate-day fasting (ADF) has gained popularity in recent years.
      The diet consists of a "fast day" where an individual consumes 0-25% of their
      energy needs, alternated with a "feast day" where a person is permitted to eat ad
      libitum. AIM: This study examined eating behavior traits of successful weight
      losers during alternate day fasting. METHODS: Obese participants ( n = 34) took
      part in 12 months of ADF and were grouped into a high (>=5%) or low-weight-loss
      (<5%) group post-treatment. RESULTS: The high-weight-loss group demonstrated
      increased ( p = 0.04) fullness, decreased ( p = 0.03) hunger, increased dietary
      protein intake (15% to 20% of kcal, p = 0.04), and better adherence to fast-day
      calorie goals. CONCLUSIONS: Thus, individuals who achieve clinically significant
      weight loss with ADF demonstrate improved satiety, increased protein intake, and
      better adherence to fast-day calorie goals.

PMID- 29353536
TI  - A progressive three-phase innovation to medical education in the United States.
AB  - : The practice of medicine has changed greatly over the past 100 years, yet the
      structure of undergraduate medical education has evolved very little. Many
      schools have modified their curricula to incorporate problem-based learning and
      organ systems-based curricula, but few schools have adequately addressed rising
      tuition costs. Undergraduate medical education has become cost-prohibitive for
      students interested in primary care. In the meanwhile, the concept of a separate
      dedicated intern year is outdated and mired in waste despite remaining a
      requirement for several hospital-based and surgical specialties. Described here
      is an innovative approach to medical education which reduces tuition costs and
      maximizes efficiency, based on principals already employed by several schools.
      This integrated curriculum, first suggested by the author in 2010, keeps the
      current USMLE system in place, exposes medical students to patient care earlier,
      expands and incorporates the 'intern' year into a four-year medical training
      program, provides more time for students to decide on a specialty, and allows
      residency programs to acquire fully-licensed practitioners with greater clinical
      experience than the status quo. ABBREVIATIONS: MCAT: Medical college admission
      test; USMLE: US medical licensing examination.

PMID- 29353537
TI  - Exposure to impulse noise at an explosives company: a case study.
AB  - Impulse noise encountered in workplaces is a threat to hearing. The aim of this
      study was to assess the occupational exposure to impulse noise produced by
      detonation of dynamite on the premises of an explosives company. Test points were
      located on the blast test area (inside and outside the bunker) and in work
      buildings across the site. Noise propagation measurement was performed during 130
      blast tests at nine measurement points. At every point, at least 10 separate
      measurements of A-weighted equivalent sound pressure level (LAeq), maximum A
      weighted sound pressure level (LAmax) and C-weighted peak sound pressure level
      (LCpeak) were made. Noise recorded in the blast test area exceeded occupational
      exposure limits (OELs). Noise levels measured in buildings did not exceed OELs.
      Results of the survey showed that for 62% of respondents, impulse noise causes
      difficulties in performing work. The most commonly reported symptoms include
      headaches, nervousness and irritability.

PMID- 29353539
TI  - Translation and validation of Simplified Chinese version of the Pain
      Catastrophizing Scale in chronic pain patients: Education may matter.
AB  - Objective Pain catastrophizing is linked to many aspects of pain perception and
      defines a unique dimension in predicting pain intensity and physical disability.
      Pain Catastrophizing Scale (PCS) is an effective, validated,self-report measure,
      commonly used in clinical trials. Here, we present a Simplified Chinese PCS (SC
      PCS) version developed in Chinese patients suffering from chronic pain. Methods
      The SC-PCS was generated in five steps and tested on an initial patient cohort (N
      = 30). A convenience sample (N = 200) of in-hospital patients with non-malignant
      pain lasting for more than 12 weeks were recruited for the study, of which 81
      completed 5 additional pain questionnaires. A subset (N = 24) of the patients
      completed an additional SC-PCS, 10 days after the initial query to assess test
      retest validation. Results Intra-class correlations coefficient indicated high
      reproducibility and temporal consistency, (0.97), for the total score. Cronbach's
      alpha determined high internal consistency across the SC-PCS total score and its
      three subscales (0.87, 0.85, 0.62, and 0.65). The SC-PCS total score moderately
      or weakly (R = -0.2 to 0.49), but significantly, correlated with other
      measurements, such as pain Visual Analog Scale, Beck Depression Inventory, Pain
      Anxiety Symptoms Scales, Positive and Negative Affect Schedule, and education. We
      used exploratory factor analysis to examine the dimensionality of the SC-PCS,
      which indicated instability of the current three-factor model. However, a
      confirmatory factor analysis indicated that the three-factor model had the best
      goodness-fitting. Conclusions We demonstrate the successful translational
      adaptation from English to Simplified Chinese as well as the reliability and
      validity of SC-PCS. An important discovery was education level significantly
      correlated with SC-PCS, identifying a future consideration for other cross
      cultural development of self-reported measures.

PMID- 29353538
TI  - Lithium reverses mechanical allodynia through a mu opioid-dependent mechanism.
AB  - Background Lithium is widely used to treat bipolar disorders and displays mood
      stabilizing properties. In addition, lithium relieves painful cluster headaches
      and has a strong analgesic effect in neuropathic pain rat models. Objectives To
      investigate the analgesic effect of lithium on the cuff model of neuropathic
      pain. Methods We used behavioral and pharmacological approaches to study the
      analgesic effect of a single injection of lithium in wild-type and mu opioid
      receptor (MOR) null cuffed neuropathic mice. Mass spectrometry and enzyme-linked
      immunosorbent assay allowed to measure the levels of endogenous MOR agonist beta
      endorphin as well as monoamines in brain and plasma samples 4 h after lithium
      administration. Results A single injection of lithium chloride (100 mg/kg, ip)
      alleviated mechanical allodynia for 24 h, and this effect was absent in MOR null
      neuropathic mice. Biochemical analyses highlight a significant increase in beta
      endorphin levels by 30% in the brain of lithium-treated mice compared to
      controls. No variation of beta-endorphin was detected in the blood. Conclusions
      Together, our results provide evidence that lithium induces a long-lasting
      analgesia in neuropathic mice presumably through elevated brain levels of beta
      endorphin and the activation of MORs.

PMID- 29353541
TI  - Volumetric abnormalities of the brain in a rat model of recurrent headache.
AB  - Voxel-based morphometry is used to detect structural brain changes in patients
      with migraine. However, the relevance of migraine and structural changes is not
      clear. This study investigated structural brain abnormalities based on voxel
      based morphometry using a rat model of recurrent headache. The rat model was
      established by infusing an inflammatory soup through supradural catheters in
      conscious male rats. Rats were subgrouped according to the frequency and duration
      of the inflammatory soup infusion. Tactile sensory testing was conducted prior to
      infusion of the inflammatory soup or saline. The periorbital tactile thresholds
      in the high-frequency inflammatory soup stimulation group declined persistently
      from day 5. Increased white matter volume was observed in the rats three weeks
      after inflammatory soup stimulation, brainstem in the in the low-frequency
      inflammatory soup-infusion group and cortex in the high-frequency inflammatory
      soup-infusion group. After six weeks' stimulation, rats showed gray matter volume
      changes. The brain structural abnormalities recovered after the stimulation was
      stopped in the low-frequency inflammatory soup-infused rats and persisted even
      after the high-frequency inflammatory soup stimulus stopped. The changes of voxel
      based morphometry in migraineurs may be the result of recurrent headache.
      Cognition, memory, and learning may play an important role in the chronification
      of migraines. Reducing migraine attacks has the promise of preventing chronicity
      of migraine.

PMID- 29353540
TI  - Involvement of neutrophils and interleukin-18 in nociception in a mouse model of
      muscle pain.
AB  - Muscle pain is a common condition that relates to various pathologies. Muscle
      overuse induces muscle pain, and neutrophils are key players in pain production.
      Neutrophils also play a central role in chronic pain by secreting interleukin
      (IL)-18. The aim of this study was to investigate the involvement of neutrophils
      and IL-18 in a mouse model of muscle pain. The right hind leg muscles of BALB/c
      mice were stimulated electrically to induce excessive muscle contraction. The
      left hind leg muscles were not stimulated. The pressure pain threshold, number of
      neutrophils, and IL-18 levels were investigated. Furthermore, the effects of the
      IL-18-binding protein and Brilliant Blue G on pain were investigated. In
      stimulated muscles, pressure pain thresholds decreased, and neutrophil and IL-18
      levels increased compared with that in non-stimulated muscles. The administration
      of IL-18-binding protein and Brilliant Blue G attenuated hyperalgesia caused by
      excessive muscle contraction. These results suggest that increased IL-18
      secretion from larger numbers of neutrophils elicits mechanical hyperalgesia.

PMID- 29353542
TI  - Dark clouds in co-creation, and their silver linings practical challenges we
      faced in a participatory project in a resource-constrained community in India,
      and how we overcame (some of) them.
AB  - BACKGROUND: While any type of field-based research is challenging, building
      action-oriented, participatory research in resource-constrained settings can be
      even more so. OBJECTIVE: In this article, we aim to examine and provide insights
      into some of the practical challenges that were faced during the course of a
      participatory project based in two non-notified slums in Bangalore, India, aiming
      to build solutions to indoor air pollution from cooking on traditional cook
      stoves. METHODS: The article draws upon experiences of the authors as field
      researchers engaged in a community-based project that adopted an exploratory,
      iterative design to its planning and implementation, which involved community
      visits, semi-structured interviews, prioritization workshops, community forums,
      photo voice activities, chulha-building sessions and cooking trials. RESULTS: The
      main obstacles to field work were linked to fostering open, continued dialogue
      with the community, aimed at bridging the gap between the 'scientific' and the
      'local' worlds. Language and cultural barriers led to a reliance on interpreters,
      which affected both the quality of the interaction as well as the relationship
      between the researchers and the community that was built out of that interaction.
      The transience in housing and location of members of the community also led to
      difficulties in following up on incomplete information. Furthermore, facilitating
      meaningful participation from the people within the context of restricted
      resources, differing priorities, and socio-cultural diversity was particularly
      challenging. These were further compounded by the constraints of time and
      finances brought on by the embeddedness of the project within institutional
      frameworks and conventional research requirements of a fixed, pre-planned and
      externally determined focus, timeline, activities and benchmarks for the project.
      CONCLUSIONS: This article calls for revisiting of scientific conventions and
      funding prerequisites, in order to create spaces that support flexible, emergent
      and adaptive field-based research projects which can respond effectively to the
      needs and priorities of the community.

PMID- 29353544
TI  - A Comprehensive Profile of Those Who Have Health-Related Apps.
AB  - This study investigated sociodemographic, health-related, technological, and
      motivational factors associated with having health-related apps. Focusing on
      motivational factors, this study chose five general healthy intentions (about
      fruit, vegetable, and soda intake, weight control, and amount of exercise) and
      examined whether those with intention to change their current state (change
      group) differ from those who want to maintain (maintain group) or pay no
      attention to their current state (no attention group). A secondary analysis of
      data from the Health Information National Trends Survey 4 (Cycle 4), collected
      from a representative sample of U.S. adults aged 18 years or older, was
      conducted. Only responses from Internet users were analyzed ( N = 2,802).
      Regarding sociodemographics, younger individuals and those with higher income
      were more likely to have health apps. Hispanics and the less educated were less
      likely to have health apps. Also, technological factors, such as smartphone and
      Wi-Fi use, were associated with having apps. Regarding motivational factors,
      Model 1 (no attention group as a reference group) showed differences in having
      apps between those who wanted to change their weight and those who paid no
      attention. Model 2 (maintain group as a reference group) revealed a difference
      between those who tried to change the amount of exercise and those who maintained
      it. The findings provided a comprehensive profile of those with health apps in
      the United States: non-Hispanic young people with higher income, higher
      education, a smartphone, and a Wi-Fi connection who want to change (but not
      maintain) their weight and amount of exercise.

PMID- 29353543
TI  - Tai Chi Improves Cognition and Plasma BDNF in Older Adults With Mild Cognitive
      Impairment: A Randomized Controlled Trial.
AB  - BACKGROUND: Effects of Tai Chi (TC) on specific cognitive function and mechanisms
      by which TC may improve cognition in older adults with amnestic mild cognitive
      impairment (a-MCI) remain unknown. OBJECTIVE: To examine the effects of TC on
      cognitive functions and plasma biomarkers (brain-derived neurotrophic factor
      [BDNF], tumor necrosis factor-alpha [TNF-alpha], and interleukin-10 [IL-10]) in a
      MCI. METHODS: A total of 66 older adults with a-MCI (mean age = 67.9 years) were
      randomized to either a TC (n = 33) or a control group (n = 33). Participants in
      the TC group learned TC with a certified instructor and then practiced at home
      for 50 min/session, 3 times/wk for 6 months. The control group received
      educational material that covered information related to cognition. The primary
      outcome was cognitive performance, including Logical Memory (LM) delayed recall,
      Block Design, Digit Span, and Trail Making Test B minus A (TMT B-A). The
      secondary outcomes were plasma biomarkers, including BDNF, TNF-alpha, and IL-10.
      RESULTS: At the end of the trial, performance on the LM and TMT B-A was
      significantly better in the TC group compared with the control group after
      adjusting for age, gender, and education ( P < .05). Plasma BDNF level was
      significantly increased for the TC group, whereas the other outcome measures were
      similar between the 2 groups after adjusting for age and gender ( P < .05).
      CONCLUSIONS: TC training significantly improved memory and the mental switching
      component of executive function in older adults with a-MCI, possibly via an
      upregulation of BDNF.

PMID- 29353545
TI  - Prevalence of Bystander Intervention Opportunities and Behaviors Among U.S. Army
      Soldiers.
AB  - The bystander intervention model is one approach utilized to reduce risky
      behaviors within the U.S. Army; however, it is unclear how frequently soldiers
      experience opportunities to intervene and whether they already intervene in such
      situations. The present analysis aims to ascertain frequencies for opportunities
      to intervene and the rates at which soldiers intervene when presented with such
      opportunities. Soldiers ( N = 286) were asked whether they had witnessed
      particular risky behavior scenarios of interest to the Army (i.e., suicide
      related behaviors, alcohol misuse, or sexual harassment/assault) during the
      previous 2 months and whether they had intervened in those scenarios. Prevalence
      rates within this sample were calculated to determine the frequency of such
      situations and subsequent interventions. Logistic regression was used to
      ascertain any differences in witnessing scenarios by demographic groups. Nearly
      half (46.8%) of the soldiers reported witnessing at least one scenario involving
      risky behaviors. Most soldiers who witnessed an event relating to suicide or
      alcohol misuse also reported consistently intervening (87.9% and 74.4%,
      respectively), whereas just half consistently intervened in response to scenarios
      relating to sexual harassment/assault (49.2%). Lower ranking soldiers were twice
      as likely as higher ranks to witness scenarios involving alcohol misuse (odds
      ratio = 2.18, 95% confidence interval [1.11, 4.26]) and sexual harassment/assault
      (odds ratio = 2.21, 95% confidence interval [1.05, 4.62]). These data indicate
      that soldiers regularly encounter opportunities to intervene in risky behaviors,
      and while a majority intervened in such scenarios, more training is warranted,
      particularly around sexual assault and harassment. This supports the notion that
      bystander intervention training is a worthwhile investment for the Army.

PMID- 29353546
TI  - Who Starts the Conversation and Who Receives Preexposure Prophylaxis (PrEP)? A
      Brief Online Survey of Medical Providers' PrEP Practices.
AB  - Uptake of preexposure prophylaxis (PrEP) has been slow, but is increasing.
      Although PrEP is indicated for many patients, it has been concentrated among men
      who have sex with men (MSM). Awareness of PrEP is limited among non-MSM
      individuals, and among some MSM. As such, individuals at risk for HIV who are
      unaware of PrEP must rely on their medical providers to initiate conversations
      about PrEP. Members of a national professional organization of HIV specialists
      with prescribing privileges, including physicians, nurse practitioners, and
      physician assistants, participated in an online survey ( n = 342) to characterize
      their PrEP prescribing behaviors and the demographic membership of their PrEP
      patients. Results indicated that when discussing PrEP with their patients,
      providers who more frequently initiated these conversations had a higher
      percentage of non-MSM patients in their PrEP caseload (e.g., women, people who
      inject drugs, transgender patients). Encouraging providers to initiate
      discussions about PrEP with their patients and helping them locate support to
      offset the cost may help increase uptake, particularly among at-risk patients who
      are underrepresented in PrEP adoption.

PMID- 29353548
TI  - Clinical Toxicology Expert Reviewers 2017.

PMID- 29353547
TI  - Understanding the Process of Prioritizing Fruit and Vegetable Purchases in
      Families With Low Incomes: "A Peach May Not Fill You Up as Much as Hamburger".
AB  - Fruits and vegetables (F&V) are an important component of a healthy diet, but few
      children are meeting the recommended number of servings. Children from families
      with limited resources may be least likely to meet the recommendation. This study
      was designed to understand the strategies and priorities of families with low
      income related to purchasing F&V. We conducted qualitative, in-depth telephone
      interviews with low-income parents of elementary school-aged children as part of
      a random sample of parents participating in a telephone survey who agreed to be
      contacted for an in-depth interview. Interview transcripts were coded based on
      predetermined codes that were informed by the research questions. F&V were not
      considered staples by parents and cost was one of the main concerns. Parents
      equated F&V with fresh F&V. Interventions encouraging F&V purchasing by families
      with low income need to find new ways to address the issue of cost, including
      advocating for F&V in all forms (fresh, frozen, canned, and dried).

PMID- 29353549
TI  - Delineation of the frequency and boundary of chromosomal copy number variations
      in paediatric neuroblastoma.
AB  - Neuroblastoma, the most common solid tumour in early childhood, is characterized
      by very frequent chromosomal copy number variations (CNVs). While chromosome 2p
      amplification, 17q gain, 1p and 11q deletion in human neuroblastoma tissues are
      well-known, the exact frequencies and boundaries of the chromosomal CNVs have not
      been delineated. We analysed the publicly available single nucleotide
      polymorphism (SNP) array data which were originally generated by the
      Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
      initiative, defined the frequencies and boundaries of chromosomes 2p11.2 - 2p25.3
      amplification, 17q11.1-17q25.3 gain, 1p13.3-1p36.33 deletion and 11q13.3-11q25
      deletion in neuroblastoma tissues, and identified chromosome 7q14.1
      (Chr7:38254795-38346971) and chromosome 14q11.2 (Chr14:21637401-22024617)
      deletion in blood and bone marrow samples from neuroblastoma patients, but not in
      tumour tissues. Kaplan Meier analysis showed that double deletion of Chr7q14.1
      and Chr14q11.2 correlated with poor prognosis in MYCN gene amplified
      neuroblastoma patients. In conclusion, the oncogenes amplified or gained and
      tumour suppressor genes deleted within the boundaries of chromosomal CNVs in
      tumour tissues should be studied for their roles in tumourigenesis and as
      therapeutic targets. Focal deletions of Chr7q14.1 and Chr14q11.2 together in
      blood and bone marrow samples from neuroblastoma patients can be used as a marker
      for poorer prognosis and more aggressive therapies.

PMID- 29353550
TI  - ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple
      sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a complex disease with new drugs becoming
      available in the past years. There is a need for a reference tool compiling
      current data to aid professionals in treatment decisions. OBJECTIVES: To develop
      an evidence-based clinical practice guideline for the pharmacological treatment
      of people with MS. METHODS: This guideline has been developed using the Grading
      of Recommendations Assessment, Development and Evaluation (GRADE) methodology and
      following the updated EAN recommendations. Clinical questions were formulated in
      Patients-Intervention-Comparator-Outcome (PICO) format and outcomes were
      prioritized. The quality of evidence was rated into four categories according to
      the risk of bias. The recommendations with assigned strength (strong and weak)
      were formulated based on the quality of evidence and the risk-benefit balance.
      Consensus between the panelists was reached by use of the modified nominal group
      technique. RESULTS: A total of 10 questions were agreed, encompassing treatment
      efficacy, response criteria, strategies to address suboptimal response and safety
      concerns and treatment strategies in MS and pregnancy. The guideline takes into
      account all disease-modifying drugs approved by the European Medicine Agency
      (EMA) at the time of publication. A total of 21 recommendations were agreed by
      the guideline working group after three rounds of consensus. CONCLUSION: The
      present guideline will enable homogeneity of treatment decisions across Europe.

PMID- 29353551
TI  - Public understanding of One Health messages: The role of temporal framing.
AB  - Building on research in motivated reasoning and framing in science communication,
      we examine how messages that vary attribution of responsibility (human vs animal)
      and temporal orientation (now vs in the next 10 years) for wildlife disease risk
      influence individuals' conservation intentions. We conducted a randomized
      experiment with a nationally representative sample of US adults ( N = 355), which
      revealed that for people low in biospheric concern, messages that highlighted
      both human responsibility for and the imminent nature of the risk failed to
      enhance conservation intentions compared with messages highlighting animal
      responsibility. However, when messages highlighting human responsibility placed
      the risk in a temporally distal frame, conservation intentions increased among
      people low in biospheric concern. We assess the underlying mechanism of this
      effect and discuss the value of temporal framing in overcoming motivated
      skepticism to improve science communication.

PMID- 29353552
TI  - Micronutrient powders to combat anaemia in young children: do they work?
AB  - In 2016, the World Health Organization (WHO) recommended point-of-use
      fortification of complementary foods with iron-containing micronutrient powders
      to improve iron status and reduce anaemia in children at risk of anaemia. This
      recommendation continues to be debated. In a recent trial among Kenyan children
      aged 12-36 months, we found no evidence that daily point-of-use fortification was
      efficacious in improving haemoglobin concentration or plasma iron markers. An
      updated meta-analysis indicated that, on average, in an arbitrarily selected
      setting and with adherence as obtained under trial conditions, one may expect a
      small increase in haemoglobin concentration in preschool children, with the upper
      limit of the 95% CI virtually excluding an effect beyond 5.5 g/L. In the present
      paper, we elaborate on the interpretation of these findings and the meta-analyses
      that formed the basis for the WHO guidelines. In particular, we draw attention to
      the phenomenon that small group differences in the distribution of continuous
      outcomes (haemoglobin concentration, ferritin concentrations) can give a false
      impression of relatively large effects on the prevalence of the dichotomised
      outcomes (anaemia, iron deficiency).Please see related articles:
      https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0839-z ,
      https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0867-8.

PMID- 29353554
TI  - Knowledge, attitudes and practices related to cystic echinococcosis endemicity in
      Pakistan.
AB  - BACKGROUND: Cystic echinococcosis (CE) is a human and animal health problem in
      many endemic areas worldwide. It is considered a neglected zoonotic disease
      caused by the larval form (hydatid cyst) of Echinococcus spp. tapeworm. There are
      limited studies on echinococcosis in Pakistan. METHODS: A cross-sectional survey
      was conducted to find out recent knowledge, attitudes and practices on the
      occurrence of cystic echinococcosis in butchers and dog owners in both urban and
      rural areas of Rawalpindi/Islamabad regions, Pakistan. The quantitative data was
      collected in the form of questionnaires to investigate the knowledge and
      awareness of CE among community members and their routine practices that  were
      behind the factors involved in hydatid cyst infection. The practices and
      infrastructure of abattoirs/butcher shops and their role in transmission of
      cystic echinococcosis were also evaluated in the present study. RESULTS: The
      participants involved in the study were dog owners and people who kept animals. A
      total of 400 people were interviewed and 289 questionnaires were received. The
      results showed that only 4.1% of people have heard about the disease, and 58.1%
      were closely associated with dogs. Sixty-three percent of dogs in study area were
      consuming uncooked organs (e.g. liver, lung, etc.) of slaughtered animals, while
      100% of dogs at butcher shops were consuming uncooked organs. Home slaughtering
      was common in 20.06%. Among butchers, 32.3% had heard about zoonoses and 7.61%
      knew about CE. The statistical analysis showed that there was highly significant
      difference (P < 0.05) among most of the practices that were associated with the
      prevalence of CE. CONCLUSIONS: It  was concluded from the present study that, the
      knowledge and awareness of CE among people of Rawalpindi/Islamabad were low.
      Because of dogs and poor knowledge of CE among community members and butchers,
      the transmission of echinococcosis is facilitated. Therefore, there is urgent
      need to strengthen awareness and health education among people, as well as proper
      practices related to the CE not only in the study area, but also in other areas
      of Pakistan.

PMID- 29353553
TI  - Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint
      blockade for metastatic renal cell carcinoma.
AB  - BACKGROUND: An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with
      worse outcomes in several malignancies. However, its role with contemporary
      immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR
      in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB.
      METHODS: We examined NLR at baseline and 6 (+/-2) weeks later in 142 patients
      treated between 2009 and 2017 at Dana-Farber Cancer Institute (Boston, USA).
      Landmark analysis at 6 weeks was conducted to explore the prognostic value of
      relative NLR change on overall survival (OS), progression-free survival (PFS),
      and objective response rate (ORR). Cox and logistic regression models allowed for
      adjustment of line of therapy, number of IMDC risk factors, histology and
      baseline NLR. RESULTS: Median follow up was 16.6 months (range: 0.7-67.8). Median
      duration on therapy was 5.1 months (<1-61.4). IMDC risk groups were: 18%
      favorable, 60% intermediate, 23% poor-risk. Forty-four percent were on first-line
      ICB and 56% on 2nd line or more. Median NLR was 3.9 (1.3-42.4) at baseline and
      4.1 (1.1-96.4) at week 6. Patients with a higher baseline NLR showed a trend
      toward lower ORR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was a
      significantly stronger predictor of all three outcomes than baseline NLR.
      Relative NLR change by >=25% from baseline to 6 weeks after ICB therapy was
      associated with reduced ORR and an independent prognostic factor for PFS (p <
      0.001) and OS (p = 0.004), whereas a decrease in NLR by >=25% was associated with
      improved outcomes. CONCLUSIONS: Early decline and NLR at 6 weeks are associated
      with significantly improved outcomes in mRCC patients treated with ICB. The
      prognostic value of the readily-available NLR warrants larger, prospective
      validation.

PMID- 29353555
TI  - Racial/ethnic differences in the association between alcohol use and mortality
      among men living with HIV.
AB  - BACKGROUND: Increasing alcohol use is associated with increased risk of mortality
      among patients living with HIV (PLWH). This association varies by race/ethnicity
      among general outpatients, but racial/ethnic variation has not been investigated
      among PLWH, among whom racial/ethnic minorities are disproportionately
      represented. METHODS: VA electronic health record data from the Veterans Aging
      Cohort Study (2008-2012) were used to describe and compare mortality rates across
      race/ethnicity and levels of alcohol use defined by the Alcohol Use Disorders
      Identification Test-Consumption (AUDIT-C) questionnaire. Within each
      racial/ethnic group, Cox proportional hazards models, adjusted for age, disease
      severity, and comorbidities, compared mortality risk for moderate-risk (AUDIT-C =
      4-7) and high-risk (AUDIT-C >= 8) relative to lower-risk (AUDIT-C = 1-3) alcohol
      use. RESULTS: Mean follow-up time among black (n = 8518), Hispanic (n = 1353),
      and white (n = 7368) male PLWH with documented AUDIT-C screening (n = 17,239) was
      4.3 years. Black PLWH had the highest mortality rate among patients reporting
      lower-risk alcohol use (2.9/100 person-years) relative to Hispanic and white PLWH
      (1.8 and 2.3, respectively) (p value for overall comparison = 0.011). Mortality
      risk was increased for patients reporting high-risk relative to lower-risk
      alcohol use in all racial/ethnic groups [black adjusted hazard ratio (AHR) =
      1.36, 95% confidence interval (CI) 1.12-1.66; Hispanic AHR = 2.18, 95% CI 1.30
      3.64; and white AHR = 2.04, 95% CI 1.61-2.58]. For only white PLWH, mortality
      risk was increased for patients reporting moderate-relative to lower-risk alcohol
      use (black AHR = 1.09, 95% CI 0.93-1.27; Hispanic AHR = 1.36, 95% CI 0.89-2.09;
      white AHR = 1.51, 95% CI 1.28-1.77). CONCLUSION: Among all PLWH, mortality risk
      was increased among patients reporting high-risk alcohol use across all
      racial/ethnic groups, but mortality risk was only increased among patients
      reporting moderate-risk relative to lower-risk alcohol use among white PLWH, and
      black patients appeared to have higher mortality risk relative to white patients
      at lower-risk levels of alcohol use. Findings of the present study further
      underscore the need to address unhealthy alcohol use among PLWH, and future
      research is needed to understand mechanisms underlying observed differences.

PMID- 29353556
TI  - Providing straw to allow exploratory behaviour in a pig experimental system does
      not modify putative indicators of positive welfare: peripheral oxytocin and
      serotonin.
AB  - Numerous studies have shown that providing straw to pigs can reduce undesirable
      behaviours such as aggression, tail biting and stereotypy. The measurement of
      various neuromodulators can be helpful in assessing the development of positive
      behaviours and overall animal welfare. The oxytocin release is frequently linked
      to positive emotions and positive welfare. It has been suggested that oxytocin
      modulates the serotoninergic system. This study aims to investigate the potential
      effect of straw provision in pigs on peripheral levels of oxytocin and serotonin.
      In total, 18 mini-pigs were involved in an exploratory study conducted in two
      parallel groups, Enriched (n=10) and Control (n=8) groups. Pigs were divided by
      group and housed in pens of two individuals. Straw was provided continuously only
      in Enriched group and renewed each day for 2 weeks. Two blood samples were drawn
      from each animal 5 to 10 min before providing the straw, and 15 min after
      providing straw, during the 1st week, to analyse peripheral changes in oxytocin
      and serotonin before and after straw provision, and determine the existence of a
      putative short-term effect. The same procedure was carried out for Control group,
      without straw provision. Long-term effects of straw provision were also examined
      using blood samples drawn at the same hour from each animal in the 2nd and 3rd
      weeks. During this time, animals had the permanent possibility to explore the
      straw in Enriched group but not in Control group. At the end of each week, one
      animal-keeper completed two visual analogue scales for each mini-pig regarding
      the difficulty/ease to work with and handle it and its trust in humans. Results
      showed peripheral oxytocin increases in both groups after 2 weeks (P=0.02).
      Results did not demonstrate any effect of providing straw to allow exploratory
      behaviour on peripheral serotonin. Other results were not significant. This
      preliminary study explored the relationship between peripheral oxytocin and
      serotonin and the presence of straw that allow pigs to perform exploratory
      behaviour, suggesting that there was no relationship between them. Some future
      studies may include crossing oxytocin and serotonin with other parameters, such
      as behavioural measures, to obtain more information about the true state of the
      animal and any possible relationship with pig welfare.

PMID- 29353558
TI  - Mixed-up about how to diagnose and treat mixed features in major depressive
      episodes - CORRIGENDUM.

PMID- 29353557
TI  - Validation and Evaluation of Antimicrobial Orders Indication for Use.

PMID- 29353559
TI  - What should health insurance cover? A comparison of Israeli and US approaches to
      benefit design under national health reform.
AB  - What health insurance should cover and pay for represents one of the most complex
      questions in national health policy. Israel shares with the US reliance on a
      regulated insurance market and we compare the approaches of the two countries
      regarding determining health benefits. Based on review and analysis of
      literature, laws and policy in the United States and Israel. The Israeli
      experience consists of selection of a starting point for defining coverage;
      calculating the expected cost of covered benefits; and creating a mechanism for
      updating covered benefits within a defined budget. In implementing the Affordable
      Care Act, the US rejected a comprehensive and detailed approach to essential
      health benefits. Instead, federal regulators established broadly worded minimum
      standards that can be supplemented through more stringent state laws and insurer
      discretion. Notwithstanding differences between the two systems, the elements of
      the Israeli approach to coverage, which has stood the test of time, may provide a
      basis for the United States as it renews its health reform debate and considers
      delegating decisions about coverage to the states. Israel can learn to emulate
      the more forceful regulation of supplemental and private insurance that
      characterizes health policy in the United States.

PMID- 29353560
TI  - Does non-echo-planar diffusion-weighted magnetic resonance imaging have a role in
      assisting the clinical diagnosis of cholesteatoma in selected cases?
AB  - OBJECTIVE: To determine the diagnostic performance of diffusion-weighted magnetic
      resonance imaging in the assessment of patients with suspected, but not
      clinically evident, cholesteatoma. METHODS: A retrospective analysis of a
      prospectively collected database of non-echo-planar diffusion-weighted magnetic
      resonance imaging studies (using a half-Fourier single-shot turbo-spin echo
      sequence) was conducted. Clinical records were retrospectively reviewed to
      determine indications for imaging and operative findings. Seventy-eight
      investigations in 74 patients with suspected cholesteatoma aged 5.7-79.2 years
      (mean, 41.7 years) were identified. Operative confirmation was available in 44
      ears. Diagnostic accuracy of the imaging technique was calculated using operative
      findings as a 'gold standard'. Sensitivity of the investigation was examined via
      comparison with clinically evident cholesteatoma. RESULTS: The accuracy of
      diffusion-weighted magnetic resonance imaging in assessment of suspected
      cholesteatoma was 63.6 per cent. The imaging technique was significantly less
      accurate in assessment of suspected cholesteatoma than clinically evident disease
      (p < 0.001). CONCLUSION: Computed tomography and diffusion-weighted magnetic
      resonance imaging may be complementary in assessment of suspected cholesteatoma,
      but should be used with caution, and clinical judgement is paramount.

PMID- 29353561
TI  - Is birth weight associated with blood pressure among African children and
      adolescents? A systematic review.
AB  - : There is substantial evidence of an inverse association between birth weight
      and later blood pressure (BP) in populations from high-income countries, but
      whether this applies in low-income countries, where causes of low birth weight
      are different, is not certain. OBJECTIVE: We conducted a review of the evidence
      on the relationship between birth weight and BP among African children and
      adolescents. Medline, EMBASE, Global Health and Web of Science databases were
      searched for publications to October 2016. Papers reporting the relationship
      between birth weight and BP among African children and adolescents were assessed.
      Bibliographies were searched for further relevant publications. Selected papers
      were summarized following the preferred reporting items for systematic review and
      meta-analysis (PRISMA) guidelines. In total, 16 papers from 13 studies conducted
      in nine African countries (Nigeria, Republic of Seychelles, Gambia, Democratic
      Republic of Congo, Cameroon, South Africa, Algeria, Zimbabwe and Angola) were
      reviewed. Eight studies were cohorts, while five were cross-sectional. The
      relationship between birth weight and later BP varied with age of the
      participants. Studies in neonates showed a consistently positive association,
      while predominantly inverse associations were seen among children, and studies in
      adolescents were inconsistent. Based on the limited number of studies identified,
      the relationship between birth weight and later BP may vary with age in African
      children and adolescents. Not all studies adequately controlled for confounding,
      notably gender or age. Whether the inverse relationship between birth weight and
      BP in later life observed in Western settings is also seen in Africa remains
      unclear.

PMID- 29353563
TI  - Retrieval is central to the distinctive function of episodic memory.
AB  - Episodic retrieval is heavily and asymmetrically dependent on the temporal order
      of the remembered events. This effect, or rather the underlying structure which
      it reflects, is a distinctive feature missing from the account in the target
      article. This structure explains significant successes and failures of episodic
      retrieval, and it has clear consequences for the fitness of the organism
      extending beyond communication.

PMID- 29353564
TI  - An adaptive function of mental time travel: Motivating farsighted decisions.
AB  - The episodic memory system allows us to experience the emotions of past,
      counterfactual, and prospective events. We outline how this phenomenological
      experience can convey motivational incentives for farsighted decisions. In this
      way, we challenge important arguments for Mahr & Csibra's (M&C's) conclusion that
      future-oriented mental time travel is unlikely to be a central function of
      episodic memory.

PMID- 29353562
TI  - Impaired cognitive plasticity and goal-directed control in adolescent obsessive
      compulsive disorder.
AB  - BACKGROUND: Youths with obsessive-compulsive disorder (OCD) experience severe
      distress and impaired functioning at school and at home. Critical cognitive
      domains for daily functioning and academic success are learning, memory,
      cognitive flexibility and goal-directed behavioural control. Performance in these
      important domains among teenagers with OCD was therefore investigated in this
      study. METHODS: A total of 36 youths with OCD and 36 healthy comparison subjects
      completed two memory tasks: Pattern Recognition Memory (PRM) and Paired
      Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED)
      task to quantitatively gauge learning as well as cognitive flexibility. A subset
      of 30 participants of each group also completed a Differential-Outcome Effect
      (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of
      goal-directed and habitual behavioural control. RESULTS: Adolescent OCD patients
      showed a significant learning and memory impairment. Compared with healthy
      comparison subjects, they made more errors on PRM and PAL and in the first stages
      of IED involving discrimination and reversal learning. Patients were also slower
      to learn about contingencies in the DOE task and were less sensitive to outcome
      devaluation, suggesting an impairment in goal-directed control. CONCLUSIONS: This
      study advances the characterization of juvenile OCD. Patients demonstrated
      impairments in all learning and memory tasks. We also provide the first
      experimental evidence of impaired goal-directed control and lack of cognitive
      plasticity early in the development of OCD. The extent to which the impairments
      in these cognitive domains impact academic performance and symptom development
      warrants further investigation.

PMID- 29353565
TI  - Episodic memory must be grounded in reality in order to be useful in
      communication.
AB  - The primary function of episodic memory is to provide reliable information about
      reality that is essential for surviving and navigating in an environment. The
      communicative function of episodic memory "sits on top of" this basic function
      but does not, in itself, explain it in its totality (but may explain particular
      aspects such as its sensitivity to source credibility).

PMID- 29353566
TI  - Episodic memory isn't essentially autonoetic.
AB  - I argue that the function attributed to episodic memory by Mahr & Csibra (M&C) -
      that is, grounding one's claims to epistemic authority over past events - fails
      to support the essentially autonoetic character of such memories. I suggest, in
      contrast, that episodic event memories are sometimes purely first order,
      sometimes autonoetic, depending on relevance in the context.

PMID- 29353567
TI  - Why episodic memory may not be for communication.
AB  - Three serious challenges to Mahr & Csibra's (M&C's) proposal are presented.
      First, we argue that the epistemic attitude that they claim is unique to
      remembering also applies to some forms of imaginative simulations that aren't
      memories. Second, we argue that their account cannot accommodate critical
      neuropsychological evidence. Finally, we argue that their proposal looks
      unconvincing when compared to more parsimonious evolutionary accounts.

PMID- 29353568
TI  - The dynamics of episodic memory functions.
AB  - There is no doubt that episodic memory serves communicative functions, but Mahr &
      Csibra (M&C) overlook that this is not the only function served by memories of
      past events. Autobiographical memory research has identified several other
      functions, including purely directive functions. The functionality of episodic
      memory is not stable across situations; it varies dynamically with the demands of
      the retrieval context.

PMID- 29353569
TI  - Episodic memory is as much about communicating as it is about relating to others.
AB  - Mahr & Csibra (M&C) provide extensive evidence for the communicative function of
      episodic memory, suggesting that the malleability of human memory is in large
      part due to its communicative dimension. I argue that emphasizing the relational
      motivations involved in communication provides a more proximal explanation for
      why our memories are as malleable.

PMID- 29353570
TI  - The communicative function of destination memory.
AB  - Mahr & Csibra's (M&C's) proposal that episodic memory has a role in communicative
      interaction is innovative. However, the model would be strengthened by the
      inclusion of the construct of destination memory. Destination memory refers to
      the ability to remember to whom one has sent information. Research has
      demonstrated that this ability is essential for communicative efficacy and daily
      interactions with others.

PMID- 29353571
TI  - More to episodic memory than epistemic assertion: The role of social bonds and
      interpersonal connection.
AB  - Remembering is dynamically entangled in conversations. The communicative function
      of episodic memory can be epistemic, as suggested by Mahr & Csibra (M&C).
      However, remembering can have genuinely social functions, specifically, the
      creation or consolidation of interpersonal relationships. Autonoesis, a distinct
      feature of episodic memory, is more likely to have evolved in the service of
      social binding than of epistemic assertiveness.

PMID- 29353572
TI  - Remembered events are unexpected.
AB  - We remember a small proportion of our experiences as events. Are these events
      selected because they are useful and can be proven true, or rather because they
      are unexpected?

PMID- 29353573
TI  - Sleep to be social: The critical role of sleep and memory for social interaction.
AB  - Humans are highly social animals who critically need to remember information from
      social episodes in order to successfully navigate future social interactions. We
      propose that such episodic memories about social encounters are processed during
      sleep, following the learning experience, with sleep abstracting and
      consolidating social gist knowledge (e.g., beliefs, first impressions, or
      stereotypes) about others that supports relationships and interpersonal
      communication.

PMID- 29353574
TI  - Episodic memory and consciousness in antisocial personality disorder and conduct
      disorder.
AB  - Episodic memory is one of the most significant sources of information of humans.
      It entails cooperative and linguistic skills and, as Mahr & Csibra (M&C) note,
      the capacity to ground veridical beliefs about the past. In some psychiatric
      disorders (antisocial personality disorder and conduct disorder), it was found
      that the habit of lying is associated with episodic memory and consciousness
      deficits.

PMID- 29353575
TI  - The sociocultural functions of episodic memory.
AB  - The functional use of episodic memories to claim epistemic truth must be placed
      within sociocultural contexts in which certain truths are privileged. Episodic
      memories are shared, evaluated, and understood within sociocultural interactions,
      creating both individual and group identities. These negotiated identities
      provide the foundation from which epistemic claims to truth can be made.

PMID- 29353576
TI  - "Truth be told" - Semantic memory as the scaffold for veridical communication.
AB  - Theoretical accounts placing episodic memory as central to constructive and
      communicative functions neglect the role of semantic memory. We argue that the
      decontextualized nature of semantic schemas largely supersedes the computational
      bottleneck and error-prone nature of episodic memory. Rather, neuroimaging and
      neuropsychological evidence of episodic-semantic interactions suggest that an
      integrative framework more accurately captures the mechanisms underpinning social
      communication.

PMID- 29353577
TI  - Episodic memory and the witness trump card.
AB  - We accept Mahr & Csibra's (M&C's) causal claim that episodic memory provides
      humans with the means for evaluating the veracity of reports about non-occurrent
      events. We reject their evolutionary argument that this is the proper function of
      episodic memory. We explore three intriguing implications of the causal claim,
      for cognitive neuropsychology, comparative psychology, and philosophy.

PMID- 29353578
TI  - Encoding third-person epistemic states contributes to episodic reconstruction of
      memories.
AB  - We propose an extension to Mahr & Csibra's (M&C's) theory. For successful
      episodic memory formation, potentially relevant aspects of a situation need to be
      identified and encoded online and retained for prospective interactions. To be
      maximally convincing, the communicator not only has to encode not just any
      contextual detail, but also has to track information in relation to social
      partners.

PMID- 29353579
TI  - Episodic memory solves both social and nonsocial problems, and evolved to fulfill
      many different functions.
AB  - The episodic memory system is flexible and complex, and likely evolved in
      response to a wide range of survival-relevant problems in our evolutionary past,
      both social and nonsocial. Episodic memory allows us to recollect and infer
      details that may have seemed trivial on encoding, but are now known to be
      relevant. This memory aids humans in navigating their uncertain environment.

PMID- 29353580
TI  - Using episodic memory to gauge implicit and/or indeterminate social commitments.
AB  - In discussing Mahr & Csibra's (M&C's) observations about the role of episodic
      memory in grounding social commitments, we propose that episodic memory is
      especially useful for gauging cases of implicit commitment and cases in which the
      content of a commitment is indeterminate. We conclude with some thoughts about
      how commitment may relate to the evolution of episodic memory.

PMID- 29353581
TI  - Epistemic authority, episodic memory, and the sense of self.
AB  - The distinctive feature of episodic memory is autonoesis, the feeling that one's
      awareness of particular past events is grounded in firsthand experience.
      Autonoesis guides us in sharing our experiences of past events, not by telling us
      when our credibility is at stake, but by telling us what others will find
      informative; it also supports the sense of an enduring self.

PMID- 29353582
TI  - Carving event and episodic memory at their joints.
AB  - Mahr & Csibra (M&C) argue that event and episodic memories share the same
      scenario construction process. I think this way of carving up the distinction
      throws the baby out with the bathwater. If there is a substantive difference
      between event and episodic memory, it is based on a difference in the
      construction process and how they are organized, respectively.

PMID- 29353583
TI  - Autonoesis and reconstruction in episodic memory: Is remembering systematically
      misleading?
AB  - Mahr & Csibra (M&C) view autonoesis as being essential to episodic memories and
      construction as being essential to the process of episodic remembering. These
      views imply that episodic memory is systematically misleading, not because it
      often misinforms us about the past, but rather because it often misinforms us
      about how it informs us about the past.

PMID- 29353584
TI  - False memories, nonbelieved memories, and the unresolved primacy of
      communication.
AB  - Mahr & Csibra (M&C) make a compelling case for a communicative function of
      episodic remembering, but a less compelling case that this is its primary
      function. Questions arise on whether confirming their predictions would support
      their account sufficiently, on the communicative function of preserving rich,
      nonbelieved memories, and on the epistemic benefits of developing false memories
      via the acceptance of misinformation.

PMID- 29353585
TI  - Developmental roots of episodic memory.
AB  - Two arguments imply that Mahr & Csibra's (M&C's) functional theory is
      insufficient as an explanation of episodic memory: (1) The developmental course
      supports a different social cultural division of episodic and semantic memory,
      and (2) the existence of long-term autobiographical memory is not explained in
      the functional theory but can be seen in a broader cultural framework.

PMID- 29353586
TI  - Misconceptions about adaptive function.
AB  - Mahr & Csibra (M&C) fail to make the important distinction between why a trait
      originally evolved, why it was maintained over time, and what its current utility
      is. Here we point out that episodic memory may have originally evolved as a by
      product of a general metarepresentational capacity, and that it may have current
      functions beyond the communicative domain.

PMID- 29353587
TI  - Morgan's canon is not evidence.
AB  - Mahr & Csibra's (M&C's) account of the communicative function of episodic memory
      relies more heavily on the case against episodic memory in nonhumans than their
      description suggests. Although the communicative function of episodic memory may
      be accurate as it pertains to human behaviour, we question whether Morgan's canon
      is a suitable foundation on which to build theories of supposedly human-specific
      traits.

PMID- 29353588
TI  - Enhanced action control as a prior function of episodic memory.
AB  - Improved control of agency is likely to be a prior and more important function of
      episodic memory than the epistemic-communicative role pinpointed by Mahr & Csibra
      (M&C). Taking the memory trace upon which scenario construction is based to be a
      stored internal model produced in past perceptual processing promises to provide
      a better account of autonoetic character than metarepresentational embedding.

PMID- 29353589
TI  - Confabulation and epistemic authority.
AB  - Mahr & Csibra (M&C) claim that episodic remembering's autonoetic character serves
      as an indicator of epistemic authority. This proposal is difficult to reconcile
      with the existence of confabulation errors - where participants fabricate
      memories of experiences that never happened to them. Making confabulation errors
      damages one's epistemic authority, but these false memories have an autonoetic
      character.

PMID- 29353590
TI  - Constructive episodic simulation, flexible recombination, and memory errors.
AB  - According to Mahr & Csibra (M&C), the view that the constructive nature of
      episodic memory is related to its role in simulating future events has difficulty
      explaining why memory is often accurate. We hold this view, but disagree with
      their conclusion. Here we consider ideas and evidence regarding flexible
      recombination processes in episodic retrieval that accommodate both accuracy and
      distortion.

PMID- 29353591
TI  - Beyond communication: Episodic memory is key to the self in time.
AB  - Mahr & Csibra (M&C) propose that episodic memory evolved to support epistemic
      authority in social communication. We argue for a more parsimonious
      interpretation whereby episodic memory subserves a broader preparatory function
      for both social and non-social behavior. We conclude by highlighting that
      functional accounts of episodic memory may need to consider the complex
      interrelations between self and subjective time.

PMID- 29353592
TI  - Emotional memories and how your life may depend upon them.
AB  - In this commentary, we discuss how one's internal body state and the appraisals
      an individual utilizes at encoding alter later episodic memory irrespective of
      social discourse. We suggest that the purpose of episodic memory is originally
      the preservation of the self, which may have been co-opted to navigating the
      social world.

PMID- 29353593
TI  - What is it to remember?
AB  - In response to the commentaries, we clarify and defend our characterization of
      both the nature and function of episodic memory. Regarding the nature of episodic
      memory, we extend the distinction between event and episodic memory and discuss
      the relational role of episodic memory. We also address arguments against our
      characterization of autonoesis and argue that, while self-referential, it needs
      to be distinguished from an agentive notion of self. Regarding the function of
      episodic memory, we review arguments about the relation between future mental
      time travel and memory veridicality; clarify the relation between autonoesis,
      veridicality, and confidence; and finally discuss the role of episodic memory in
      diachronic commitments.

PMID- 29353594
TI  - Doing without metarepresentation: Scenario construction explains the epistemic
      generativity and privileged status of episodic memory.
AB  - Episodic memories are distinct from semantic memories in that they are
      epistemically generative and privileged. Whereas Mahr & Csibra (M&C) develop a
      metarepresentational account of epistemic vigilance, we propose an explanation
      that builds on our notion of scenario construction: The way an event of the past
      is presented in episodic memory recall explains the epistemic generativity and
      privilegedness of episodic memory.

PMID- 29353595
TI  - Autonoesis and dissociative identity disorder.
AB  - Dissociative identity disorder is characterised by the presence in one individual
      of two or more alternative personality states (alters). For such individuals, the
      memory representation of a particular event can have full episodic, autonoetic
      status for one alter, while having the status of knowledge or even being
      inaccessible to a second alter. This phenomenon appears to create difficulties
      for a purely representational theory and is presented to Mahr & Csibra (M&C) for
      their consideration.

PMID- 29353596
TI  - What psychology and cognitive neuroscience know about the communicative function
      of memory.
AB  - Mahr & Csibra (M&C) include interesting ideas about the nature of memory from
      outside of the field of cognitive psychology and cognitive neuroscience. However,
      the target article's inaccurate claims about those fields limit its usefulness. I
      briefly review the most serious omissions and distortions of the literature by
      the target article, including its misrepresentation of event memory, and offer
      suggestions for forwarding the goal of understanding the communicative function
      of memory.

PMID- 29353597
TI  - Medicarpin induces lipolysis via activation of Protein Kinase A in brown
      adipocytes.
AB  - Natural pterocarpan Medicarpin (Med) has been shown to have various beneficial
      biological roles, including inhibition of osteoclastogenesis, stimulation of bone
      regeneration and induction of apoptosis. However, the effect of the Med on
      lipolysis in adipocytes has not been reported. Here, we show the effect of Med on
      lipolysis in different mouse adipocytes and elucidate the underlying mechanism.
      We observed that Med treatment promoted release of glycerol in the media.
      Differentiated mouse brown adipose tissue cells were treated with Med. RNA-Seq
      analysis was performed to elucidate the effect of med and subsequently was
      confirmed by qRT-PCR and western blotting analyses. Med treatment increased both
      protein and gene expression levels of hormone-sensitive lipase (Hsl) and adipose
      triglyceride lipase (Atgl), which are two critical enzymes necessary for
      lipolysis. Mechanistic study showed that Med activates Protein Kinase A (PKA) and
      phosphorylates Hsl at PKA target position at Serine660. Silencing of PKA gene by
      short interfering RNA attenuated the Med-induced increase in glycerol release and
      Hsl phosphorylation. The results unveil that Med boosts lipolysis via a PKA
      dependent pathway in adipocytes and may provide a possible avenue of further
      research of Med mediated reduction of body fat. [BMB Reports 2018; 51(5): 249
      254].

PMID- 29353598
TI  - New role of LTR-retrotransposons for emergence and expansion of disease
      resistance genes and high-copy gene families in plants.
AB  - Long terminal repeat retrotransposons (LTR-Rs) are major elements creating new
      genome structure for expansion of plant genomes. However, in addition to the
      genome expansion, the role of LTR-Rs has been unexplored. In this study, we
      constructed new reference genome sequences of two pepper species (Capsicum
      baccatum and C. chinense), and updated the reference genome of C. annuum. We
      focused on the study for speciation of Capsicum spp. and its driving forces. We
      found that chromosomal translocation, unequal amplification of LTR-Rs, and recent
      gene duplications in the pepper genomes as major evolutionary forces for
      diversification of Capsicum spp. Specifically, our analyses revealed that the
      nucleotide-binding and leucine-rich-repeat proteins (NLRs) were massively created
      by LTR-R-driven retroduplication. These retoduplicated NLRs were abundant in
      higher plants, and most of them were lineage-specific. The retroduplication was a
      main process for creation of functional disease-resistance genes in Solanaceae
      plants. In addition, 4-10% of whole genes including highly amplified families
      such as MADS-box and cytochrome P450 emerged by the retroduplication in the
      plants. Our study provides new insight into creation of disease-resistance genes
      and high-copy number gene families by retroduplication in plants. [BMB Reports
      2018; 51(2): 55-56].

PMID- 29353599
TI  - MicroRNAs as critical regulators of the endothelial to mesenchymal transition in
      vascular biology.
AB  - The endothelial to mesenchymal transition (EndMT) is a newly recognized,
      fundamental biological process involved in development and tissue regeneration,
      as well as pathological processes such as the complications of diabetes, fibrosis
      and pulmonary arterial hypertension. The EndMT process is tightly controlled by
      diverse signaling networks, similar to the epithelial to mesenchymal transition.
      Accumulating evidence suggests that microRNAs (miRNAs) are key regulators of this
      network, with the capacity to target multiple messenger RNAs involved in the
      EndMT process as well as in the regulation of disease progression. Thus, it is
      highly important to understand the molecular basis of miRNA control of EndMT.
      This review highlights the current fund of knowledge regarding the known links
      between miRNAs and the EndMT process, with a focus on the mechanism that
      regulates associated signaling pathways and discusses the potential for the EndMT
      as a therapeutic target to treat many diseases. [BMB Reports 2018; 51(2): 65-72].

PMID- 29353600
TI  - Regulation of Hippo signaling by actin remodeling.
AB  - The Hippo signaling pathway controls nuclear accumulation and stability of the
      transcriptional coregulator YAP and its paralog TAZ. The activity of Hippo-YAP
      signaling is influenced not only by biochemical signals, but also by cell shape
      and mechanical tension transmitted through cell-cell junctions and cell-matrix
      adhesions. Data accumulated thus far indicates that the actin cytoskeleton is a
      key mediator of the regulation of Hippo-YAP signaling by means of a variety of
      biochemical and mechanical cues. In this review, we have outlined the role of
      actin dynamics and actin-associated proteins in the regulation of Hippo-YAP
      signaling. In addition, we discuss actinmediated regulation of YAP/TAZ activity
      independent of the core Hippo kinases MST and LATS. Although our understanding of
      the link between Hippo-YAP signaling and the actin cytoskeleton is progressing
      rapidly, many open questions remain. [BMB Reports 2018; 51(3): 151-156].

PMID- 29353601
TI  - Interval Cancers in Colorectal Cancer Screening Programs.

PMID- 29353603
TI  - Oral fexinidazole for human African trypanosomiasis.

PMID- 29353602
TI  - A Rare Cause of Chronic Anemia and Recurrent Bowel Obstruction.

PMID- 29353604
TI  - Scaling up integration of health services.

PMID- 29353605
TI  - Chronic liver disease: scavenger hunt for novel therapies.

PMID- 29353606
TI  - Offline: Time to act on minimum unit pricing of alcohol.

PMID- 29353607
TI  - Malaysia: a refugee conundrum.

PMID- 29353608
TI  - Iranian protests and Rouhanicare.

PMID- 29353609
TI  - Doctors disagree with proposed medical bill in India.

PMID- 29353610
TI  - A literary pain scale.

PMID- 29353611
TI  - Natalia Kanem: lifelong advocate for women's health and rights.

PMID- 29353612
TI  - Changing minds about changing behaviour.

PMID- 29353613
TI  - Treaty to prohibit nuclear weapons and Germany's global health responsibility.

PMID- 29353614
TI  - Saving the Joint Comprehensive Plan of Action: full of hope or just hopeless?

PMID- 29353615
TI  - Singapore should play a strong leadership role in global health.

PMID- 29353616
TI  - Questions regarding the CONCERN trial - Authors' reply.

PMID- 29353617
TI  - Questions regarding the CONCERN trial.

PMID- 29353618
TI  - Translation of the link between cancer and obesity to patients.

PMID- 29353619
TI  - GRECCAR2 trial: details worthy of more attention - Authors' reply.

PMID- 29353620
TI  - GRECCAR2 trial: details worthy of more attention.

PMID- 29353621
TI  - Pitfalls of the healthy vaccinee effect.

PMID- 29353622
TI  - Pitfalls of the healthy vaccinee effect - Authors' reply.

PMID- 29353623
TI  - Children and social media.

PMID- 29353624
TI  - Sanctioning the most vulnerable-a failed foreign policy.

PMID- 29353625
TI  - A new vaccine for typhoid control.

PMID- 29353627
TI  - Reflexology in the management of chemotherapy induced peripheral neuropathy: A
      pilot randomized controlled trial.
AB  - PURPOSE: The current experimental study aimed to evaluate the effectiveness of
      reflexology on the management of symptoms and functions of chemotherapy-induced
      peripheral neuropathy (CIPN) in cancer patients. METHOD: This study was conducted
      as a randomized controlled trial in 60 patients (30 experimental and 30 control
      patients) who had chemotherapy-induced Grade II-IV peripheral neuropathy
      complaints from July 2013 to November 2015. Data were collected using the patient
      identification form, European Organization for the Research and Treatment of
      Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy
      (EORTC-CIPN-20) form, and BPI (used for related chemotherapy-induced peripheral
      neuropathy symptoms). RESULTS: The majority of the patients were being treated
      for gastrointestinal or breast cancer and were primarily receiving Eloxatine- or
      taxane-based treatment. It was found that reflexology applications did not lead
      to differences in either group in terms of peripheral neuropathy severity and
      incidence (p > 0.05) and only led to improvement in sensory functions in the
      experimental group (p < 0.05). CONCLUSIONS: It was determined that reflexology is
      not an effective method in the management of patients' activity levels, walking
      ability etc. and motor, autonomic functions related CIPN, but reflexology is
      effective method in the management of patients' sensory functions related CIPN.
      Key Words: Peripheral neuropathy, reflexology, chemotherapy, EORTC QLQ-CIPN-20,
      BPI.

PMID- 29353626
TI  - Hearing loss and tinnitus in survivors with chemotherapy-induced neuropathy.
AB  - PURPOSE: The purpose of this study was to evaluate for differences in
      demographic, clinical, and pain characteristics, as well as measures of
      sensation, balance, perceived stress, symptom burden, and quality of life (QOL)
      among survivors who received neurotoxic chemotherapy (CTX) and who reported only
      chemotherapy-induced neuropathy (CIN, n = 217), CIN and hearing loss (CIN/HL, n =
      69), or CIN, hearing loss, and tinnitus (CIN/HL/TIN, n = 85). We hypothesized
      that as the number of neurotoxicities increased, survivors would have worse
      outcomes. METHODS: Survivors were recruited from throughout the San Francisco Bay
      area. Survivors completed self-report questionnaires for pain and other symptoms,
      stress and QOL. Objective measures were assessed at an in person visit. RESULTS:
      Compared to survivors with only CIN, survivors with all three neurotoxicities
      were less likely to be female and less likely to report child care
      responsibilities. In addition, survivors with all three neurtoxicities had higher
      worst pain scores, greater loss of protective sensation, and worse timed get up
      and go scores. These survivors reported higher state anxiety and depression and
      poorer QOL. For some outcomes (e.g., longer duration of CIN, self-reported
      balance problems), significantly worse outcomes were found for the survivors with
      CIN/HL and CIN/HL/TIN compared to those with only CIN. CONCLUSIONS: Our findings
      suggest that compared to survivors with only CIN, survivors with CIN/HL/TIN are
      at increased risk for the most severe symptom burden, significant problems
      associated with sensory loss and changes in balance, as well as significant
      decrements in all aspects of QOL.

PMID- 29353629
TI  - Experiences of caregivers of patients with metastatic cancer: What can we learn
      from them to better support them?
AB  - PURPOSE: Family caregivers of cancer patients often face strains within their
      role and report various unmet needs. The aim of this qualitative study was to
      examine metastatic cancer caregivers' experiences within their role. METHODS: A
      cross-sectional study using focus group interviews with caregivers of metastatic
      cancer patients (n = 17) recruited from an oncology hospital in Cyprus was
      conducted. Data were analysed following the content analysis approach with
      inductive coding for the development of themes. RESULTS: Content analysis
      identified four categories of themes, which were further divided into sub
      categories: difficulties in their role as caregivers, impact of cancer diagnosis
      on interpersonal relationships, support and strength resources and unmet needs.
      Findings replicated existing evidence regarding caregiving difficulties and unmet
      needs in caregivers with a different cultural background and provided further
      evidence for similarities and variations within caregiving experiences relating
      mostly to caregiver-patient relationships. Caregivers also highlighted coping and
      support resources that they effectively use for better adjustment to their role.
      CONCLUSION: The identified variations in experiences in relation to participants'
      characteristics, in addition to the information about preferred by caregivers
      coping and support resources provide a direction for future efforts to develop
      interventions for this population.

PMID- 29353628
TI  - Diet in women with breast cancer compared to healthy controls - What is the
      difference?
AB  - PURPOSE: After a cancer diagnosis, patients often change their lifestyle in order
      to improve health. The aim of this study was to examine whether women with breast
      cancer had changed their diet two years after the diagnosis, and to compare their
      diet with that of healthy female blood donors. METHODS: Patients (n = 180),
      median age 58 years (range 37-78), and 101 controls, median age 57 years (age 43
      75) answered questions about consumption of alcohol, 36 different food items, and
      information like age, body mass index (BMI), marital status, and years of
      education. RESULTS: Forty patients (22%) had changed their diet. Comparing all
      patients with controls, significantly more patients avoided alcohol, p = 0.0005,
      and 3 of 36 food items; smoked food, p = 0.04, and milk and other dairy products,
      p = 0.02 and p = <0.0001, respectively. Based on BMI, 50% of all the patients
      reported overweight or obesity. Breast cancer treatment explained 5.7% of the
      total variance in scores for changing diet, where chemotherapy was the sole
      significant predictor, p = 0.04. CONCLUSION: Two years after a breast cancer
      diagnosis, most women (78%) maintained their diet, which was largely similar to
      the controls. Fifty percent of the patients reported overweight or obesity.

PMID- 29353630
TI  - Illness cognitions and the associated socio-demographic and clinical factors in
      Chinese women with breast cancer.
AB  - PURPOSE: Illness cognitions are important mediators between disease and
      psychological adjustment. Evidence related to illness cognitions among patients
      with breast cancer remains limited. The purpose of this study was to examine
      illness cognitions among Chinese women with breast cancer and associations with
      socio-demographic and clinical factors. METHODS: A cross-sectional study was
      carried out involving 313 women with breast cancer recruited from a general
      hospital and a social cancer support club in Beijing from October 2016 to May
      2017. Data were collected using the Illness Cognition Questionnaire. RESULTS:
      Participants reported positive overall cognition regarding breast cancer
      (helplessness, 13.70 +/- 4.24; acceptance, 16.86 +/- 4.30; perceived benefits,
      17.93 +/- 3.86). A multiple regression model indicated that six factors were
      associated with illness cognitions: treatment phase of disease, having no
      children, not returning to work (positive associations with helplessness,
      negative associations with acceptance; age (negative associations with
      helplessness, positive associations with acceptance); treatment phase of disease,
      having no medical insurance (negative associations with perceived benefit); and
      disease duration (positive associations with acceptance). CONCLUSIONS: This study
      reports on the presence of different illness cognitions in Chinese women with
      breast cancer and the associated factors, and the results could help oncology
      medical and nursing staff identify risk factors for poor emotional adjustment to
      breast cancer and the patients who may benefit from interventions aimed at
      improving the presence of positive illness cognitions.

PMID- 29353632
TI  - Health related quality of life during cancer treatment: Perspectives of young
      adult (23-39 years) cancer survivors and primary informal caregivers.
AB  - PURPOSE: There is a paucity of information regarding health related quality of
      life (HRQoL) of young adults (YAs) with cancer and caregivers. Therefore, we
      characterize YA and caregiver perspectives on the impact of cancer and its
      treatment on HRQoL. METHODS: We conducted descriptive qualitative in-depth, semi
      structured interviews with YAs receiving cancer care at an academic health center
      in Albuquerque, New Mexico (USA) and primary informal caregivers. The interviews,
      conducted from September through December 2015, focused on perspectives on the
      impact of the disease and its treatment in terms of physical and emotional
      effects, coping, and strategies to enhance HRQoL. We used an iterative thematic
      analysis approach to identify emergent themes and create a coding structure.
      RESULTS: We reached thematic saturation after interviewing 8 YAs and 8
      caregivers. YAs and caregivers discussed cancer triggered challenges such as
      anxiety, depression, isolation, fear, and financial hardships. YAs and caregivers
      coped by maintaining positive perspectives, relying on friends and family, and
      prayer. Caregivers discussed how expectations for and experiences of a "good day"
      changed depending on their loved ones' stage of cancer treatment. YAs navigated
      challenges by focusing on activities and thoughts that provided meaning to their
      lives. YAs and caregivers suggested strategies to enhance HRQoL through
      patient/provider communication, support services, and decision making tools as
      potential mechanisms for grounding patient-centered interventions to improve
      cancer care. CONCLUSIONS: Implications include the development and evaluation of
      informational and behavioral interventions tailored and targeted to address the
      pragmatic needs of YAs undergoing cancer treatment and informal caregivers.

PMID- 29353631
TI  - Efficacy of Plantago major, chlorhexidine 0.12% and sodium bicarbonate 5%
      solution in the treatment of oral mucositis in cancer patients with solid tumour:
      A feasibility randomised triple-blind phase III clinical trial.
AB  - PURPOSE: Oral mucositis is one of the most common adverse effects of chemotherapy
      and radiotherapy. The aim of this study was to compare the efficacy of Plantago
      major extract versus chlorhexidine 0.12% versus sodium bicarbonate 5% in the
      symptomatic treatment of chemotherapy-induced oral mucositis in solid tumour
      cancer patients. METHOD: Multicentre randomised controlled trial estimated sample
      of 45 solid tumour patients with grade II-III mucositis. The participants were
      randomised to one of three treatments, consisting of sodium bicarbonate 5%
      aqueous solution together with: an additional dose of sodium bicarbonate 5%
      aqueous solution, Plantago major extract, or chlorhexidine 0.12%. The primary
      outcomes were severity of mucositis, pain intensity, oral intake capacity and
      quality of life. The independent variable was treatment group, and confounders
      included sociodemographic data, neutrophil count, chemotherapy drug and dose
      received. RESULTS: Of the 50 patients enrolled, 68% (n = 34) achieved grade 0
      mucositis (none), with those using the double sodium bicarbonate rinse healing in
      five days on average (95% CI 3.9, 6.5) versus seven days (95% CI 5.3, 9,0) for
      the chlorhexidine group and seven days (95% CI 5.3, 8.5) for the Plantago major
      group. The pain experienced by the participants lessened over the 14 days of
      treatment, but differences in pain intensity between the three groups did not
      show statistical significance (p = 0.762). CONCLUSIONS: Healing time was shorter
      with the double sodium bicarbonate solution compared to the other two rinses, but
      the differences were not significant. Our results suggest it may be time to
      reconsider the use of Plantago major extract in the management of oral mucositis.

PMID- 29353633
TI  - Decisional balance and self-efficacy mediate the association among provider
      advice, health literacy and cervical cancer screening.
AB  - PURPOSE: Health literacy has emerged as a potential determinant of cancer
      screening, yet limited literature has investigated the pathways which health
      literacy influences Pap tests among immigrant women who experience a higher
      incidence of cervical cancer. This study aimed to test a health literacy-focused
      sociocognitive model which proposes motivational (knowledge, decisional balance)
      and volitional (self-efficacy) factors mediating the association between health
      literacy and triennial Pap tests. METHODS: Using structural equation modeling, we
      conducted a secondary analysis of baseline data obtained from a randomized
      controlled trial to promote breast and cervical cancer screenings among 560
      Korean American women 21-65 years of age. They were interviewed on demographics
      such as education and English proficiency, provider advice, health literacy,
      knowledge of cervical cancer, decisional balance for Pap tests, self-efficacy,
      and Pap test use. RESULTS: Higher health literacy predicted high level of
      knowledge and high decisional balance score, and greater self-efficacy and then
      only decisional balance and self-efficacy affected Pap tests. High level of
      knowledge predicted Pap tests through its impact on the decisional balance score.
      Receiving provider advice both directly and indirectly predicted Pap tests
      through high level of health literacy, high level of decisional balance and
      greater self-efficacy. CONCLUSIONS: Findings from this study suggest possible
      pathways through which provider advice and health literacy affect Pap tests.
      Interventions targeting immigrant women with limited English proficiency should
      consider skill-based approaches such as health literacy training, promoting
      patient-provider communications and emphasizing decisional balance and self
      efficacy as potentially sustainable ways of promoting Pap tests.

PMID- 29353636
TI  - Computer-Assisted Surgery in Facial Bipartition Surgery.
AB  - PURPOSE: Frontonasal dysplasia or median cleft syndrome is a rare condition often
      associated with transverse maxillary deficiency for which facial bipartition is
      the proper surgical treatment. This technical note describes the use and efficacy
      of 3-dimensional virtual surgical planning and patient-specific cutting guides in
      facial bipartition. MATERIALS AND METHODS: An 11-year-old boy presented with
      frontonasal dysplasia and a midline facial cleft. RESULTS: Computed tomographic
      (CT) scan visualized an intercanthal distance of 40 mm and a maxillary width at
      the second molar level of 46.2 mm. The osteotomies, amount of bone removal, and
      movement of the osteotomized bone were planned virtually based on CT findings:
      the intended postoperative intercanthal distance and maxillary width were 25.5
      and 49.6 mm, respectively. Customized cutting guides and titanium miniplates were
      manufactured. Postoperative CT scan showed an intercanthal distance of 25.5 mm
      and a maxillary width of 49.7 mm. CONCLUSION: The intercanthal distances and
      maxillary widths were similar between the simulation and postoperative CT images,
      confirming the accuracy and utility of computer-assisted surgery in facial
      bipartition.

PMID- 29353634
TI  - Differences in symptom clusters before and twelve months after breast cancer
      surgery.
AB  - PURPOSE: Given the inter-relatedness among symptoms, research efforts are focused
      on an evaluation of symptom clusters. The purposes of this study were to evaluate
      for differences in the number and types of menopausal-related symptom clusters
      assessed prior to and at 12-months after surgery using ratings of occurrence and
      severity and to evaluate for changes in these symptom clusters over time.
      METHODS: Prior to and at 12 months after surgery, 392 women with breast cancer
      completed the Menopausal Symptoms Scale. Exploratory factor analyses were used to
      identify the symptom clusters. RESULTS: Of the 392 women evaluated, the mean
      number of symptoms (out of 46) was 13.2 (+/-8.5) at enrollment and 10.9 (+/-8.2)
      at 12 months after surgery. Using occurrence and severity, three symptom clusters
      were identified prior to surgery. Five symptom clusters were identified at 12
      months following surgery. Two symptom clusters (i.e., pain/discomfort and
      hormonal) were relatively stable across both dimensions and time points. Two
      symptom clusters were relatively stable across both dimensions either prior to
      surgery (i.e., sleep/psychological/cognitive) or at 12 months after surgery
      (i.e., sleep). The other four clusters (i.e., irritability,
      psychological/cognitive, cognitive, psychological) were identified at one time
      point using a single dimension. CONCLUSIONS: While some menopausal-related
      symptom clusters were consistent across time and dimensions, the majority of
      symptoms clustered together differently depending on whether they were evaluated
      prior to or at 12 months after breast cancer surgery. An increased understanding
      of how symptom clusters change over time may assist clinicians to focus their
      symptom assessments and management strategies.

PMID- 29353635
TI  - Supporting prostate cancer survivors in primary care: Findings from a pilot trial
      of a nurse-led psycho-educational intervention (PROSPECTIV).
AB  - PURPOSE: This study sought to test the acceptability and feasibility of a nurse
      led psycho-educational intervention (NLPI) delivered in primary care to prostate
      cancer survivors, and to provide preliminary estimates of the effectiveness of
      the intervention. METHODS: Men who reported an ongoing problem with urinary,
      bowel, sexual or hormone-related functioning/vitality on a self-completion
      questionnaire were invited to participate. Participants were randomly assigned to
      the NLPI plus usual care, or to usual care alone. Recruitment and retention rates
      were assessed. Prostate-related quality of life, self-efficacy, unmet needs, and
      psychological morbidity were measured at baseline and 9 months. Health-care
      resource use data was also collected. An integrated qualitative study assessed
      experiences of the intervention. RESULTS: 61% eligible men (83/136) participated
      in the trial, with an 87% (72/83) completion rate. Interviews indicated that the
      intervention filled an important gap in care following treatment completion,
      helping men to self-manage, and improving their sense of well-being. However,
      only a small reduction in unmet needs and small improvement in self-efficacy was
      observed, and no difference in prostate-related quality of life or psychological
      morbidity. Patients receiving the NLPI recorded more primary care visits, while
      the usual care group recorded more secondary care visits. Most men (70%; (21/30))
      felt the optimal time for the intervention was around the time of
      diagnosis/before the end of treatment. CONCLUSIONS: Findings suggest a nurse-led
      psycho-educational intervention in primary care is feasible, acceptable and
      potentially useful to prostate cancer survivors.

PMID- 29353637
TI  - In Reply.

PMID- 29353639
TI  - Palliative care in liver disease: a matter of life and death.

PMID- 29353638
TI  - Submucosal surgery: novel interventions in the third space.
AB  - Traditional surgeries involve accessing body cavities, such as the abdomen and
      thorax, via incisions that divide skin and muscle. These operations result in
      postoperative pain and convalescence, and a risk of complications such as wound
      infection and hernia. The development of flexible endoscopy allowed diseases as
      varied as gastrointestinal bleeding and colon adenomas to be treated without
      incisions, but this technique is restricted by its endoluminal nature. A novel
      category of surgical endoscopic procedures has recently been developed that uses
      flexible endoscopic techniques to enter and access the submucosa of the
      gastrointestinal tract. Through this approach, the advantages of incisionless
      endoscopy can be applied to areas of the body that previously could only be
      reached with surgery. This Review introduces this new class of interventions by
      describing two examples of such submucosal surgeries for the treatment of benign
      gastrointestinal disease: per-oral endoscopic myotomy and per-oral pyloromyotomy.
      The approach to pre-procedure patient evaluation, operative technique, and the
      published outcomes are discussed, as well as potential future applications of
      similar techniques and procedures in this so-called third space.

PMID- 29353643
TI  - Cardiac Morbidity and Radiation Therapy for Breast Cancer.

PMID- 29353644
TI  - Locally Advanced Uterine Cancer: A Multimodality Model or Muddle?

PMID- 29353645
TI  - Radiation Is the Place to Start.

PMID- 29353646
TI  - Chemo First, Then Radiation, and Perhaps Surgery.

PMID- 29353647
TI  - Chemo-radiation, Then on to Surgery.

PMID- 29353648
TI  - Rescuing Spanish Radiation Therapy: The Role of Leadership and Opportunity.

PMID- 29353649
TI  - Bias of Professional Accomplishment: Another Important Concept for the Ethics of
      Clinical Research.

PMID- 29353650
TI  - Treatment Course Interruption/Delay Due to Weekend Breaks: Acknowledging and
      Confronting Personal and Professional Biases.

PMID- 29353651
TI  - Review of the First 12 Years of the American Society for Radiation Oncology
      Political Action Committee.

PMID- 29353652
TI  - Modeling of Normal Tissue Complications Using Imaging and Biomarkers After
      Radiation Therapy for Hepatocellular Carcinoma.
AB  - PURPOSE: To develop normal tissue complications (NTCP) models for hepatocellular
      cancer (HCC) patients who undergo liver radiation therapy (RT) and to evaluate
      the potential role of functional imaging and measurement of blood-based
      circulating biological markers before and during RT to improve the performance of
      these models. METHODS AND MATERIALS: The data from 192 HCC patients who had
      undergone RT from 2005 to 2014 were evaluated. Of the 192 patients, 146 had
      received stereotactic body RT (SBRT) and 46 had received conventional RT to a
      median physical tumor dose of 49.8 Gy and 50.4 Gy, respectively. The physical
      doses were converted into 2-Gy equivalents for analysis. Two approaches were
      investigated for modeling NTCP: (1) a generalized Lyman-Kutcher-Burman model; and
      (2) a generalization of the parallel architecture model. Three clinical endpoints
      were considered: the change in albumin-bilirubin (ALBI), change in Child-Pugh (C
      P) score, and grade >=3 liver enzymatic changes. Local dynamic contrast-enhanced
      magnetic resonance imaging portal venous perfusion information was used as an
      imaging biomarker for local liver function. Four candidate inflammatory cytokines
      were considered as biological markers. The imaging findings and cytokine levels
      were incorporated into NTCP modeling, and their role was evaluated using goodness
      of-fit metrics. RESULTS: Using dosimetric information only, the Lyman-Kutcher
      Burman model for the ALBI/C-P change had a steeper response curve compared with
      grade >=3 enzymatic changes. Incorporating portal venous perfusion imaging
      information into the parallel architecture model to represent functional reserve
      resulted in relatively steeper dose-response curves compared with dose-only
      models. A larger loss of perfusion function was needed for enzymatic changes
      compared with ALBI/C-P changes. Increased transforming growth factor-beta1 and
      eotaxin expression increased the trend of expected risk in both NTCP modeling
      approaches but did not reach statistical significance. CONCLUSIONS: The
      incorporation of imaging findings and biological markers into NTCP modeling of
      liver toxicity improved the estimates of expected NTCP risk compared with using
      dose-only models. In addition, such generalized NTCP models should contribute to
      a better understanding of the normal tissue response in HCC SBRT patients and
      facilitate personalized treatment.

PMID- 29353653
TI  - Fast and Binary Assay for Predicting Radiosensitivity Based on the Theory of ATM
      Nucleo-Shuttling: Development, Validation, and Performance.
AB  - PURPOSE: To examine the possibility of predicting clinical radiosensitivity by
      quantifying the nuclear forms of autophosphorylated ATM protein (pATM) via a
      specific enzyme-linked immunosorbent assay (ELISA). METHODS AND MATERIALS: This
      study was performed on 30 skin fibroblasts from 9 radioresistant patients and 21
      patients with adverse tissue reaction events. Patients were divided into 2
      groups: radioresistant (toxicity grade <2) and radiosensitive (toxicity grade
      >=2). The quantity of nuclear pATM molecules was assessed by the ELISA method at
      10 minutes and 1 hour after 2 Gy and compared with pATM immunofluorescence data.
      RESULTS: The pATM ELISA data were in quantitative agreement with the
      immunofluorescence data. A receiver operating characteristic analysis was applied
      first to 2 data sets (a training set [n=14] and a validating [n=16] set) and
      thereafter to all the data with a 2-fold cross-validation method. The assay
      showed an area under the curve value higher than 0.8, a sensitivity of 0.8, and a
      specificity ranging from 0.75 to 1, which strongly documents the predictive power
      of the pATM ELISA. CONCLUSION: This study showed that the assessment of nuclear
      pATM quantity after 2 Gy via an ELISA technique can be the basis of a predictive
      assay with the highest statistical performance among the available predictive
      approaches.

PMID- 29353655
TI  - Cost-Effectiveness of Primary Radiation Therapy Versus Radical Prostatectomy for
      Intermediate- to High-Risk Prostate Cancer.
AB  - PURPOSE: To compare, using a cost-effectiveness analysis, the quality-adjusted
      life expectancy (QALE) and cost between the 2 treatment options for intermediate-
      to high-risk prostate cancer: (1) radiation (RT) with androgen deprivation
      therapy (ADT) or (2) radical prostatectomy (RP) followed by adjuvant RT for
      patients with risk factors. METHODS AND MATERIALS: Our Markov model allowed
      patients to transition between health states with yearly probabilities of
      developing cancer recurrence and/or toxicity. Probabilities were assigned
      according to favorable intermediate, unfavorable intermediate, or high-risk
      prostate cancer groups. The primary analysis examined outcomes for patients aged
      65 years, whereas secondary analyses explored the effects of younger age,
      elevated baseline cardiovascular risk, and the use of salvage therapy. One-way
      and probabilistic sensitivity analyses were performed. RESULTS: Across all
      primary and secondary analyses, and using a wide-range of assumptions, RT + ADT
      was the preferred treatment strategy for men with intermediate- to high-risk
      prostate cancer. The QALE was higher after RT + ADT by 0.5 to 1.14 quality
      adjusted life years, compared with RP. Radiation plus ADT was cost-effective in
      all situations, falling beneath a threshold of $100,000 per quality-adjusted life
      year. Among all risk groups, a greater proportion of patients undergoing RP
      experienced single or multiple treatment toxicities. CONCLUSIONS: Radiation plus
      ADT may result in improved QALE compared with RP for intermediate- to high-risk
      prostate cancer. Although biochemical failure is similar between treatment
      groups, there is a higher rate of developing multiple toxicities among patients
      treated with upfront RP.

PMID- 29353654
TI  - Magnetic Resonance Imaging-Guided Adaptive Radiation Therapy: A "Game Changer"
      for Prostate Treatment?
AB  - Radiation therapy to the prostate involves increasingly sophisticated delivery
      techniques and changing fractionation schedules. With a low estimated alpha/beta
      ratio, a larger dose per fraction would be beneficial, with moderate
      fractionation schedules rapidly becoming a standard of care. The integration of a
      magnetic resonance imaging (MRI) scanner and linear accelerator allows for
      accurate soft tissue tracking with the capacity to replan for the anatomy of the
      day. Extreme hypofractionation schedules become a possibility using the
      potentially automated steps of autosegmentation, MRI-only workflow, and real-time
      adaptive planning. The present report reviews the steps involved in
      hypofractionated adaptive MRI-guided prostate radiation therapy and addresses the
      challenges for implementation.

PMID- 29353656
TI  - Systematic Review of Normal Tissue Complication Models Relevant to Standard
      Fractionation Radiation Therapy of the Head and Neck Region Published After the
      QUANTEC Reports.
AB  - There has recently been an increasing interest in model-based evaluation and
      comparison of different treatment options in radiation oncology studies. This is
      partly driven by the considerable technical advancements in radiation therapy of
      the last decade, leaving radiation oncologists with a multitude of options to
      consider. In lieu of randomized trials comparing all of these different treatment
      options for varying indications, which is unfeasible, treatment evaluations based
      on normal tissue complication probability (NTCP) models offer a practical
      alternative. The Quantitative Analyses of Normal Tissue Effects in the Clinic
      (QUANTEC) effort, culminating in a number of reports published in 2010, provided
      a basis for many of the since-implemented dose-response models and dose-volume
      constraints and was a key component for model-based treatment evaluations. Given
      that 7 years have passed since the QUANTEC publications and that patient-reported
      outcomes have emerged as an important consideration in recent years, an updated
      summary of the published radiation dose-response literature, which includes a
      focus on patient-reported quality of life outcomes, is warranted. Here we provide
      a systematic review of quantitative dose-response models published after January
      1, 2010 for endpoints relevant to radiation therapy for head and neck cancer,
      because these patients are typically at risk for a variety of treatment-induced
      normal tissue complications.

PMID- 29353657
TI  - Randomized, Double-Blind, Placebo-Controlled Trial of Shuanghua Baihe Tablets to
      Prevent Oral Mucositis in Patients With Nasopharyngeal Cancer Undergoing
      Chemoradiation Therapy.
AB  - PURPOSE: Oral mucositis is a common unpreventable complication associated with
      chemoradiation therapy. Shuanghua Baihe tablets have been approved by the Chinese
      Food and Drug Administration for treating recurrent oral mucosa ulceration. This
      study assessed whether Shuanghua Baihe tablets could prevent oral mucositis
      during chemoradiation therapy for locally advanced nasopharyngeal carcinoma.
      METHODS AND MATERIALS: This multicenter, randomized, double-blind, placebo
      controlled trial was conducted at 11 hospitals in China between January 22, 2014,
      and September 21, 2015. Eligible patients (N=240, 18-70 years old) with
      pathologically diagnosed locally advanced nasopharyngeal carcinoma were randomly
      assigned (computer-block randomization; 1:1) to receive Shuanghua Baihe tablets
      or a placebo (4 tablets, 3 times a day, for 7 weeks) at the initiation of
      chemoradiation therapy. Administration of Shuanghua Baihe tablets could be ended
      if grade 3 or higher oral mucositis developed and patients were unwilling to
      continue taking the drug. The primary endpoints were oral mucositis incidence and
      latency. RESULTS: The incidence of oral mucositis during this study was
      significantly lower in the Shuanghua Baihe group (85.0%; 95% confidence interval
      [CI], 78.6%-91.4%) than in the placebo group (96.6%; 95% CI, 93.4%-99.9%;
      P=.0028). The median latency period was 28 days in the Shuanghua Baihe group and
      14 days in the placebo group (hazard ratio, 0.17; 95% CI, 0.12-0.23; P<.0001).
      Compared with placebo, Shuanghua Baihe tablets significantly reduced the oral
      mucositis severity scores recorded by the investigators (Oral Mucositis Score,
      24.0 [range, 0.0-67.8] vs 57.5 [range, 0.0-98.0]; P<.0001), full-time nurses
      (Oral Assessment Guide score, 462.0 [range, 392.0-664.7] vs 520.4 [range, 392.0
      714.0]; P<.0001), and patients (score for soreness of mouth and throat, 4.0
      [range, 0-10] vs 6.0 [range, 0-10]; P<.0001). No serious adverse events were
      observed, and the incidence of mild or moderate gastrointestinal adverse events
      associated with Shuanghua Baihe tablets was 3.3%. The short-term response rate
      was similar in patients receiving Shuanghua Baihe tablets and those receiving
      placebo during chemoradiation therapy during this study. CONCLUSIONS: Shuanghua
      Baihe tablets reduced the occurrence, latency, and severity of oral mucositis in
      patients with nasopharyngeal cancer during chemoradiation therapy treatment.

PMID- 29353658
TI  - Tumor Control and Toxicity for Common Stereotactic Body Radiation Therapy Dose
      Fractionation Regimens in Stage I Non-Small Cell Lung Cancer.
AB  - PURPOSE: To examine the impact of stereotactic body radiation therapy (SBRT) dose
      on outcomes in early-stage non-small cell lung cancer in a large single
      institution series. METHODS AND MATERIALS: We reviewed 600 patients treated from
      2003 to 2012 for early-stage non-small cell lung cancer. The SBRT dose was at
      physician discretion on the basis of tumor size and location. Peripheral tumors
      were treated to 60 Gy in 3 fractions (homogeneous planning), 48-50 Gy in 4-5
      fractions, or 30-34 Gy in 1 fraction. Central tumors were treated to 50 Gy in 5
      fractions, 60 Gy in 8 fractions, or 50 Gy in 10 fractions. Patient, tumor, and
      treatment factors were assessed for their impact on patterns of failure,
      toxicity, and survival. RESULTS: An SBRT dose of 54-60 Gy in 3 fractions was
      associated with a statistically significant lower rate of local failure (LF)
      (4.3% at 2 years) compared with 30-34 Gy in 1 fraction (21%), 48-50 Gy in 4-5
      fractions (15.5%), and 50-60 Gy in 8-10 fractions (13.3%). Lower pre-SBRT
      hemoglobin and higher positron emission tomography standardized uptake value were
      also associated with LF. Nodal failure, distant failure, and overall survival
      were similar between fractionation groups. Pulmonary toxicity (crude rate, any
      grade) was slightly higher for 3 fractions (5.0%) compared with 1 (3.2%) or 4-5
      fractions (3.8%). Chest wall toxicity was also higher for 3 (23.7%) compared with
      1 (8.6%) or 4-5 (7.7%) fraction regimens. CONCLUSIONS: Although higher
      biologically equivalent dose SBRT (150-180 Gy10) may be associated with slightly
      lower LF, it was also associated with mildly increased toxicity and no difference
      in other patterns of failure or overall survival.

PMID- 29353659
TI  - Trends in Cardiac Mortality in Patients With Locally Advanced Non-Small Cell Lung
      Cancer.
AB  - PURPOSE: To use the Surveillance, Epidemiology, and End Results (SEER) database
      to compare cardiac-specific mortality (CSM) between left- and right-sided locally
      advanced non-small cell lung cancer (LA-NSCLC) patients treated with definitive
      radiation therapy; and to stratify these patients over fixed time intervals to
      assess for differences in events by treatment era. METHODS AND MATERIALS: The
      SEER database was queried for patients with stage III NSCLC who received
      radiation therapy to compare CSM between left- and right-sided primary cases at 5
      time intervals: 1988-1992, 1993-1997, 1998-2002, 2003-2007, and 2008-2012.
      Cumulative incidence of CSM was compared between left- and right-sided patients
      using Gray's test. The multivariate Fine and Gray competing risk model was used
      to compare CSM while accounting for other-cause mortality. RESULTS: Of 884,610
      lung cancer patients, 52,624 met inclusion criteria; of these, 31,549 (60%) were
      right-sided and 21,075 (40%) were left-sided. When evaluating CSM in each of the
      5 time periods, the overall incidence of CSM decreased over time. There was a
      statistically significant (P<.05) difference based on laterality in all time
      periods except 1988-1992 (P=.14). The subdistribution hazard ratio for CSM based
      on disease laterality in all time periods was 1.30 (95% confidence interval 1.18
      1.42) and did not discernibly differ by time interval. On multivariate analysis
      using the Fine and Gray competing risk model, left-sided laterality independently
      predicted for CSS from 1993 to 2007 (P<.05). CONCLUSIONS: Cardiac-specific
      mortality has decreased over time, and left-sided disease independently predicted
      for CSS during 1993-2007 but not 2008-2012. The time course of cardiac mortality
      seems to be early, consistent with other studies. These findings underscore the
      importance of minimizing cardiac irradiation during radiation treatment planning.

PMID- 29353661
TI  - In Regard to Bibault et al.

PMID- 29353660
TI  - Intraoperative Electron Radiation Therapy in Retroperitoneal Sarcoma.
AB  - PURPOSE: To report our experience with surgery, intraoperative radiation therapy
      (IORT), and external beam radiation therapy (EBRT) in retroperitoneal soft-tissue
      sarcoma. METHODS AND MATERIALS: We conducted a retrospective evaluation of 156
      patients (69 primary, 87 recurrent) treated with IORT since 1991. The dominant
      histology was dedifferentiated liposarcoma (49%); 89% of lesions were high grade.
      Median tumor size was 11 cm. Surgery resulted in gross complete resection in 92%,
      and 65% had microscopically positive margins. Median IORT dose was 15 Gy. A total
      of 114 patients (73%) received additional EBRT (preoperatively n=38,
      postoperatively n=76, median dose 45 Gy). RESULTS: Median follow-up was 38 months
      (49 months in survivors). The 3- and 5-year local control (LC) rates were 57% and
      50%, respectively. On univariate analysis, LC was significantly associated with
      primary versus recurrent status, histology, grade, Union for International Cancer
      Control (UICC) stage, resection margin, and addition of EBRT. The 5-year LC was
      71% in the primary situation and 79% after R0 resection. On multivariate analysis
      only disease status, grade, resection margin, and addition of EBRT remained
      statistically significant. The 3- and 5-year overall survival (OS) rates were 66%
      and 56%. On univariate analysis, OS was significantly associated with primary
      versus recurrent status, histology, grade, UICC stage, resection margin, and
      timing of EBRT. The 5-year OS was 63% in the primary situation and 68% after R0
      resection. On multivariate analysis only disease status, grade, and resection
      margin remained independent prognostic factors. Perioperative mortality was 1%,
      and major complications occurred in 34% (mainly wound complications).
      CONCLUSIONS: Treatment with surgery, IORT, and EBRT is feasible and resulted in
      good LC and OS, with acceptable morbidity in this unfavorable patient cohort.
      Incomplete resection and recurrent status resulted in clearly inferior outcomes.
      Reasonable efforts should be made during primary treatment to prevent the onset
      of a local recurrence.

PMID- 29353662
TI  - In Reply to Tallet et al.

PMID- 29353663
TI  - In reply to Royce.

PMID- 29353664
TI  - In Regard to Chowdhary et al.

PMID- 29353665
TI  - Erratum to: Wang SY, Kelly G, Gross C, et al. Information needs of older women
      with early-stage breast cancer when making radiation therapy decisions. Int J
      Radiat Oncol Biol Phys 2017;98:733-740.

PMID- 29353666
TI  - Erratum to: Hafeez S, McDonald F, Lalondrelle S, et al. Clinical outcomes of
      image guided adaptive hypofractionated weekly radiation therapy for bladder
      cancer in patients unsuitable for radical treatment. Int J Radiat Oncol Biol Phys
      2017;98:115-122.

PMID- 29353667
TI  - Test-retest reliability of Physical Activity Neighborhood Environment Scale among
      urban men and women in Nanjing, China.
AB  - OBJECTIVES: The identification of physical-activity-friendly built environment
      (BE) constructs is highly useful for physical activity promotion and maintenance.
      The Physical Activity Neighborhood Environment Scale (PANES) was developed for
      assessing BE correlates. However, PANES reliability has not been investigated
      among adults in China. STUDY DESIGN: A cross-sectional study. METHODS: With
      multistage sampling approaches, 1568 urban adults (aged 35-74 years) were
      recruited for the initial survey on all 17 items of PANES Chinese version (PANES
      CHN), with the survey repeated 7 days later for each participant. Intraclass
      correlation coefficient (ICC) was used to assess the test-retest reliability of
      PANES-CHN for each item. RESULTS: Totally, 1551 participants completed both
      surveys (follow-up rate = 98.9%). Among participants (mean age: 54.7 +/- 11.1
      years), 47.8% were men, 22.1% were elders, and 22.7% had >=13 years of education.
      Overall, the PANES-CHN demonstrated at least substantial reliability with ICCs
      ranging from 0.66 to 0.95 (core items), from 0.75 to 0.95 (recommended items),
      and from 0.78 to 0.87 (optional items). Similar outcomes were observed when data
      were analyzed by gender or age groups. CONCLUSION: The PANES-CHN has excellent
      test-retest reliability and thus has valuable utility for assessing urban BE
      attributes among Chinese adults.

PMID- 29353668
TI  - Impact of health literacy on diabetes outcomes: a cross-sectional study from
      Lahore, Pakistan.
AB  - OBJECTIVES: To evaluate the functional health literacy of patients with type 2
      diabetes in Lahore and its impact on glycaemic control. STUDY DESIGN: A six-month
      cross-sectional study. METHODS: Health literacy in 204 patients with diabetes was
      evaluated using a validated questionnaire (Short Test of Functional Health
      Literacy [s-TOFHLA]). RESULTS: The frequency distribution among various age
      groups (P = 0.003), education levels (P = 0.0005), socio-economic status levels
      (P = 0.0005) and glycated haemoglobin (HbA1C) levels (P = 0.0005) differed
      significantly with health literacy level. The majority of patients with diabetes
      (86.1%) with poor glycaemic control (HbA1C >9%) had inadequate health literacy
      and were more likely to have retinopathy (odds ratio = 13.1, P = 0.003). Health
      literacy levels were not significantly different when compared for antidiabetic
      therapies (P = 0.234). Significant associations were observed between predictors
      of glycaemic control (s-TOFHLA score [P = 0.0005], education status [P = 0.0005]
      and disease risks [P = 0.005]) and HbA1C, level. However, after adjusting for
      basic characteristics, only s-TOFHLA score had a significant association with
      HbA1C level (P = 0.001). CONCLUSIONS: These data suggest that inadequate health
      literacy is potentially associated with poor glycaemic control, and microvascular
      and macrovascular complications, particularly retinopathy. As such, educational
      and training programmes should be introduced to improve functional health
      literacy of patients with diabetes for better glycaemic control.

PMID- 29353669
TI  - Transmission of dengue virus from deceased donors to solid organ transplant
      recipients: case report and literature review.
AB  - Dengue fever is a vector-transmitted viral infection. Non-vectorial forms of
      transmission can occur through organ transplantation. We reviewed medical records
      of donors and recipients with suspected dengue in the first post-transplant week.
      We used serologic and molecular analysis to confirm the infection. Herein, we
      describe four cases of dengue virus transmission through solid organ
      transplantation. The recipients had positive serology and RT-PCR. Infection in
      donors was detected through serology. All cases presented with fever within the
      first week after transplantation. There were no fatal cases. After these cases,
      we implemented dengue screening with NS1 antigen detection in donors during
      dengue outbreaks, and no new cases were detected. In the literature review,
      additional cases had been published through August 2017. Transmission of Dengue
      virus can occur through organ donation. In endemic regions, it is important to
      suspect and screen for dengue in febrile and thrombocytopenic recipients in the
      postoperative period.

PMID- 29353670
TI  - Simultaneous detection of 5-fluorocytosine and 5-fluorouracil in human cells
      carrying CD/5-FC suicide gene system by using capillary zone electrophoresis.
AB  - A well-known suicide gene therapy approach, cytosine deaminase (CD) in
      combination with prodrug 5-flurocytosine (5-FC), has become an effective strategy
      of tumor treatment. However, there are short of simple and convenient detection
      methods to evaluate the efficiency of 5-FC conversion to 5-fluorouracil (5-FU) in
      human cells carrying various CD/5-FC systems. In this study, we developed an
      effective capillary zone electrophoresis (CZE) method to simultaneously measure 5
      FC and 5-FU in cells carrying CD/5-FC suicide gene system. Under the condition of
      60 mM borate buffer (pH 9.5) and 25 kV separation voltage with 0.5 psi * 15 s
      injection in 210 nm, the separation of 5-FC and 5-FU could be completely achieved
      within 15 min. The linearity of the calibration curve of standard 5-FC and 5-FU
      was in the range from 1 to 1000 MUM (r2 > 0.999) and their recoveries were 98.4%
      and 96.0%, respectively. Due to the simple sample preparation and easy detection,
      this method is suitable for the study of the conversion efficiency of CD/5-FC
      suicide gene system. It aims to intuitively evaluate CD/5-FC systems and helps to
      guide the improvement of more effective CD/5-FC suicide gene systems.

PMID- 29353671
TI  - Quantitative determination of cyclic phosphatidic acid and its carba analog in
      mouse organs and plasma using LC-MS/MS.
AB  - Cyclic phosphatidic acid (cPA), an analog of lysophosphatidic acid, is involved
      in the regulation of many cellular processes. A sensitive and specific method to
      quantify the molecular species of cPA is important for studying the physiological
      and pathophysiological roles of cPA. Here, we developed a liquid chromatography
      tandem mass spectrometry (LC-MS/MS)-based quantification method for the
      simultaneous detection of cPA species having various fatty acids (16:0, 18:0,
      18:1, and 18:2) as well as 2-carba-cPA, a chemically synthesized analog of cPA.
      Chromatography was performed using a reversed-phase C18 column. cPA species were
      detected using a triple quadrupole mass spectrometer. cPA 17:0 was used as an
      internal standard. Intra- and interday precision values (CV%) were within 10%.
      The linear range of detection for each cPA species was 0.01 MUg/mL to 5 MUg/mL,
      with correlation coefficients of 0.998 or higher. The developed method was
      applied to the quantification of cPA species in mouse plasma and organs. The
      concentrations of cPA 16:0, 18:0, and 18:1 were revealed to be significantly
      reduced in the brains of cuprizone-treated mice, a model of multiple sclerosis,
      compared with control mice. These findings could be important for understanding
      the roles of cPA in the neurodegenerative processes associated with multiple
      sclerosis.

PMID- 29353672
TI  - Dermal uptake and percutaneous penetration of organophosphate esters in a human
      skin ex vivo model.
AB  - Organophosphate esters (OPEs) are used as flame retardants, plasticizers, and as
      hydraulic fluids. They are present in indoor environments in high concentrations
      compared with other flame retardants, and human exposure is ubiquitous. In this
      study we provide data for estimating dermal uptake for eight OPEs and ranking in
      OPEs risk assessment. Dermal uptake and percutaneous penetration of the OPEs were
      studied in a Franz diffusion cell system using human skin dosed with a mixture of
      OPEs in an ethanol:toluene (4:1) solution. Large variation in penetration
      profiles was observed between the OPEs. The chlorinated OPEs tris(2
      chloroisopropyl) phosphate (TCIPP), and in particular tris(2-chloroethyl)
      phosphate (TCEP), penetrated the skin quite rapidly while tris(1,3-dichlor-2
      propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) tended to build up in
      the skin tissue and only smaller amounts permeated through the skin. For
      tris(isobutyl) phosphate (TIBP), tris(n-butyl) phosphate (TNBP), and
      tris(methylphenyl) phosphate (TMPP) the mass balance was not stable over time
      indicating possible degradation during the experimental period of 72 h. The rates
      at which OPEs permeated through the skin decreased in the order TCEP > TCIPP >=
      TBOEP > TIBP >= TNBP > TDCIPP > TPHP > TMPP. Generally, the permeation
      coefficient, kp, decreased with increasing log Kow, whereas lag time and skin
      deposition increased with log Kow. The present data indicate that dermal uptake
      is a non-negligible human exposure pathway for the majority of the studied OPEs.

PMID- 29353673
TI  - Soybean plant-based toxicity assessment and phytoremediation of soils
      contaminated by vegetable and mineral oils used in power electrical transformers.
AB  - In this work, deleterious effects in soils due to the presence of dielectric
      fluids were investigated. For this purpose, vegetable (Envirotemp(r) FR3) and
      mineral (Lubrax AV 66 IN) oils were used for simulating a set of soils
      contaminated in different oil contents (0.5, 1.0, 2.0, 2.5, 5.0, 7.5 and 10%) in
      which three 120-days soybean crop periods (SCP) were carried out using the
      species Glycine max (L.) Merr. Both soil and soybean plant samples were analysed
      on following the changes on chemical attributes, content of oils and greases
      (COG) in soils and phytotechnical characteristics of soybean plant. No
      significant changes on soil chemical attributes were found. For a 0.5% vegetable
      oil fraction, COG removals of 35, 60 and 90% were observed after the 1st, 2nd,
      and 3rd SCPs, respectively, whereas removals of 25, 40 and 70% were observed for
      0.5% mineral oil fraction after the 1st, 2nd, and 3rd SCPs, respectively. There
      was an effectively accumulated removal on all tested oil fractions as being
      proportional to the integrated 120-days SCPs, suggesting a lesser number of crops
      for a complete abatement of oil fraction in soil. A 100% recovery on the
      seedlings emergence fractions was also evidenced, revealing that at least a
      number of 7 and 9 SCPs should be applied continuously in soils contaminated by
      vegetable and mineral oils, respectively, in order to no longer jeopardize
      soybean plant growth. Finally, an empirical prediction of the number of SCPs
      necessary for the complete removal of oil from the soil was proposed.

PMID- 29353674
TI  - A novel 3D heteropoly blue type photo-Fenton-like catalyst and its ability to
      remove dye pollution.
AB  - A environment-friendly 3D inorganic heteropoly blue (HPB) Ba2Na2
      [HPWV4WVI8O40].26H2O was directly synthesized by hydrothermal method and
      characterized by means of ICP, IR, XPS, X-ray single crystal and X-ray powder
      diffraction. It was an efficient heterogeneous photo-Fenton-like catalyst to
      degrade anionic dye methyl orange under visible light irradiation. It removed
      cationic dyes methylene blue in neutral environment and rhodamine B in acidic
      condition via flocculation. The removal efficiency of methylene blue and
      rhodamine B by flocculation was more than 95%. Moreover, it could degrade methyl
      orange and flocculate rhodamine B at the same time. For MO and MO-RhB solutions,
      the degradation rates of MO in 60 min were 85.5% and 49.1%, respectively.
      Furthermore, the possible pathways for the production of active species in the MO
      degradation reaction were discussed. This is the first HPB constructed with 4e
      reduced phosphotungstate, Ba and Na ions, having the properties of photo-Fenton
      like catalyst and flocculant.

PMID- 29353675
TI  - Gas/particle partitioning, particle-size distribution of atmospheric
      polybrominated diphenyl ethers in southeast Shanghai rural area and size-resolved
      predicting model.
AB  - A size-segregated gas/particle partitioning coefficient KPi was proposed and
      evaluated in the predicting models on the basis of atmospheric polybrominated
      diphenyl ether (PBDE) field data comparing with the bulk coefficient KP. Results
      revealed that the characteristics of atmospheric PBDEs in southeast Shanghai
      rural area were generally consistent with previous investigations, suggesting
      that this investigation was representative to the present pollution status of
      atmospheric PBDEs. KPi was generally greater than bulk KP, indicating an
      overestimate of TSP (the mass concentration of total suspended particles) in the
      expression of bulk KP. In predicting models, KPi led to a significant shift in
      regression lines as compared to KP, thus it should be more cautious to
      investigate sorption mechanisms using the regression lines. The differences
      between the performances of KPi and KP were helpful to explain some phenomenon in
      predicting investigations, such as PL0 and KOA models overestimate the particle
      fractions of PBDEs and the models work better at high temperature than at low
      temperature. Our findings are important because they enabled an insight into the
      influence of particle size on predicting models.

PMID- 29353676
TI  - Mercury in a stream-lake network of Andean Patagonia (Southern Volcanic Zone):
      Partitioning and interaction with dissolved organic matter.
AB  - Lake Nahuel Huapi (NH) is a large, ultraoligotrophic deep system located in
      Nahuel Huapi National Park (NHNP) and collecting a major headwater network of
      Northwestern Patagonia (Argentina). Brazo Rincon (BR), the westernmost branch of
      NH, is close to the active volcanic formation Puyehue-Cordon Caulle. In BR,
      aquatic biota and sediments display high levels of total Hg (THg), ranging in
      contamination levels although it is an unpolluted region. In this survey, Hg
      species and fractionation were assessed in association with dissolved organic
      matter (DOM) in several aquatic systems draining to BR. THg varied between 16.8
      and 363 ng L-1, with inorganic Hg (Hg2+) contributing up to 99.8% and methyl
      mercury (MeHg) up to 2.10%. DOC levels were low (0.31-1.02 mg L-1) resulting in
      high THg:DOC and reflecting in high Hg2+ availability for binding particles
      (partitioning coefficient log Kd up to 6.03). In streams, Hg fractionation and
      speciation related directly with DOM terrestrial prints, indicating coupled Hg
      DOM inputs from the catchment. In the lake, DOM quality and photochemical and
      biological processing drive Hg fractionation, speciation and vertical levels.
      Dissolved gaseous Hg (Hg0) reached higher values in BR (up to 3.8%), particularly
      in upper lake layers where solar radiation enhances the photoreduction of Hg2+
      and Hg-DOM complexes. The environmental conditions in BR catchment promote Hg2+
      binding to abiotic particles and bioaccumulation and the production of Hg0,
      features enhancing Hg mobilization among ecosystem compartments. Overall, the
      aquatic network studied can be considered a "natural Hg hotspot" within NHNP.

PMID- 29353677
TI  - Method development for the analysis of ionophore antimicrobials in dairy manure
      to assess removal within a membrane-based treatment system.
AB  - Ionophore antimicrobials are heavily used in the livestock industries, both for
      preventing animal infection by coccidia protozoa and for increasing feed
      efficiency. Ionophores are excreted mostly unmetabolized and are released into
      the environment when manure is land-applied to fertilize croplands. Here, an
      analytical method was optimized to study the occurrences of five ionophore
      residues (monensin, lasalocid, maduramycin, salinomycin, and narasin) in dairy
      manure after solid-liquid separation and further treatment of the liquid manure
      by a membrane-based treatment system. Ionophore residues from the separated solid
      manure (dewatered manure) and suspended solids of manure slurry samples were
      extracted using ultrasonication with methanol, followed by sample clean-up using
      solid phase extraction (SPE) and subsequent analysis via liquid chromatography
      tandem mass spectrometry (LC-MS/MS). The use of an ethyl acetate and methanol
      (1:1 v:v) mixture as an SPE eluent resulted in higher recoveries and lower method
      quantitation limits (MQL), when compared to using methanol. Overall recoveries
      from separated solid manure ranged from 73 to 134%. Liquid manure fractions were
      diluted with NanopureTM water and cleaned up using SPE, where recoveries ranged
      from 51 to 100%. The developed extraction and LC-MS/MS methods were applied to
      analyze dairy manure samples subjected to an advanced manure treatment process
      involving a membrane-based filtration step (reverse osmosis). Monensin and
      lasalocid were detected at higher concentrations in the suspended solid fractions
      (4.40-420 ng/g for lasalocid and 85-1950 ng/g for monensin) compared to the
      liquid fractions (<MQL - 132 ng/mL for monensin). Monensin residues remained in
      liquid manure treated with reverse osmosis where residual concentrations were
      reduced to near 8 ng/mL.

PMID- 29353678
TI  - Cost effectiveness of phosphorus removal processes in municipal wastewater
      treatment.
AB  - Meeting stringent phosphorus (P) discharge standards remains one of the major
      challenges for wastewater utilities due to increased economic burdens associated
      with advanced (i.e., secondary, tertiary) treatment processes. In a trade-off
      between higher treatment cost and enhanced P removal, it is critical for the
      treatment plants to be able to select the most appropriate technology. To this
      end, established/emerging high performing P removal/recovery technologies (e.g.,
      Modified University of Cape Towne process, Bardenpho process, membrane
      bioreactors, IFAS-EBPR, struvite recovery, tertiary reactive media filtration)
      were identified and full-scale treatment plant designs were developed. Using
      advanced mathematical modeling techniques, six different treatment configurations
      were evaluated in terms of performance and cost effectiveness ($/lb of P
      removed). Results show that the unit cost for P removal in different treatment
      alternatives range from $42.22 to $60.88 per lb of P removed. The MUCT BNR +
      tertiary reactive media filtration proved to be one of the most cost effective
      configurations ($44.04/lb P removed) delivering an effluent with total P (TP)
      concentration of only 0.05 mg/L. Although struvite recovery resulted in
      significant reduction in biosolids P, the decrease in effluent TP was not
      sufficient to meet very stringent discharge standards.

PMID- 29353679
TI  - Effects of Fe(III)-fulvic acid on Cu removal via adsorption versus
      coprecipitation.
AB  - This study compared the sorption and extractability of Cu following adsorption
      (SOR) and coprecipitation(CPT). The effect of solution pH, Fe: organic carbon
      (OC) ratios and fulvic acid (FA) on the combined removal of Cu was investigated
      in the batch tests using Fe(III) precipitates as a sorbent. Transmission electron
      microscope (TEM) images demonstrated that the coexisting FA reduced the particle
      size of ferrihydrites as expected. Generally, more Cu was eliminated in
      coprecipitation compared with adsorption and the dissolved Cu left in solutions
      decreased as the pH increased, most of dissolved Cu was trapped at pH 6 and
      above. Meanwhile, the inhibition or promotion of Cu removal really depended on
      the different Fe: OC ratios. The addition of FA led to a further decrease of Cu
      concentrations in CPT systems with Fe/OC ratio of 1:3, however, Cu removal was
      hindered in the presence of FA in SOR systems. In the case of extraction
      experiments, the addition of l-malic acid (MA), oxalic acid (OA) and citric acid
      (CA) resulted in lower extractability of coprecipitated Cu than adsorption
      samples. The gaps in extractions were seemed to be a consequence of tight Cu
      binding in CPT products, and the more feasible desorption of Cu from the surface
      of SOR samples. Based on the results of Cu adsorption and coprecipitation,
      coprecipitation of Cu with ferrihydrites was the more effective Cu sequestration
      mechanism in the removal of Cu. These results are helpful to understand the
      complicated interactions among Fe(III), FA and Cu (II) in the natural
      environment.

PMID- 29353680
TI  - Feedback mechanisms between snow and atmospheric mercury: Results and
      observations from field campaigns on the Antarctic plateau.
AB  - The Antarctic Plateau snowpack is an important environment for the mercury
      geochemical cycle. We have extensively characterized and compared the changes in
      surface snow and atmospheric mercury concentrations that occur at Dome C. Three
      summer sampling campaigns were conducted between 2013 and 2016. The three
      campaigns had different meteorological conditions that significantly affected
      mercury deposition processes and its abundance in surface snow. In the absence of
      snow deposition events, the surface mercury concentration remained stable with
      narrow oscillations, while an increase in precipitation results in a higher
      mercury variability. The Hg concentrations detected confirm that snowfall can act
      as a mercury atmospheric scavenger. A high temporal resolution sampling
      experiment showed that surface concentration changes are connected with the
      diurnal solar radiation cycle. Mercury in surface snow is highly dynamic and it
      could decrease by up to 90% within 4/6 h. A negative relationship between surface
      snow mercury and atmospheric concentrations has been detected suggesting a mutual
      dynamic exchange between these two environments. Mercury concentrations were also
      compared with the Br concentrations in surface and deeper snow, results suggest
      that Br could have an active role in Hg deposition, particularly when air masses
      are from coastal areas. This research presents new information on the presence of
      Hg in surface and deeper snow layers, improving our understanding of atmospheric
      Hg deposition to the snow surface and the possible role of re-emission on the
      atmospheric Hg concentration.

PMID- 29353681
TI  - The error-related negativity (ERN) is an electrophysiological marker of motor
      impulsiveness on the Barratt Impulsiveness Scale (BIS-11) during adolescence.
AB  - OBJECTIVES: Previous studies have postulated that the error-related negativity
      (ERN) may reflect individual differences in impulsivity; however, none have used
      a longitudinal framework or evaluated impulsivity as a multidimensional
      construct. The current study evaluated whether ERN amplitude, measured in
      childhood and adolescence, is predictive of impulsiveness during adolescence.
      METHODS: Seventy-five children participated in this study, initially at ages 7-9
      years and again at 12-18 years. The interval between testing sessions ranged from
      5 to 9 years. The ERN was extracted in response to behavioural errors produced
      during a modified visual flanker task at both time points (i.e. childhood and
      adolescence). Participants also completed the Barratt Impulsiveness Scale - a
      measure that considers impulsiveness to comprise three core sub-traits - during
      adolescence. RESULTS: At adolescence, the ERN amplitude was significantly larger
      than during childhood. Additionally, ERN amplitude during adolescence
      significantly predicted motor impulsiveness at that time point, after controlling
      for age, gender, and the number of trials included in the ERN. In contrast, ERN
      amplitude during childhood did not uniquely predict impulsiveness during
      adolescence. CONCLUSIONS: These findings provide preliminary evidence that ERN
      amplitude is an electrophysiological marker of self-reported motor impulsiveness
      (i.e. acting without thinking) during adolescence.

PMID- 29353682
TI  - Predicting the risk of recurrent venous thromboembolism in patients with cancer:
      A prospective cohort study.
AB  - BACKGROUND: The risk of recurrent venous thromboembolism (VTE) in cancer patients
      despite anticoagulant therapy is high. Clinical factors and pro-coagulant markers
      may identify high-risk patients and guide decisions about intensifying
      anticoagulation therapy. AIMS: To evaluate whether serial measurements of pro
      coagulant markers can identify patients at high risk of recurrent VTE. METHODS:
      In this multicenter, prospective cohort study, patients with active cancer and
      acute deep vein thrombosis or pulmonary embolism were enrolled. Patients received
      standard low-molecular-weight heparin therapy and were followed for 6 months. D
      dimer and soluble P-selectin levels were measured at baseline and 1, 4, 5, 12,
      and 24 weeks post treatment initiation. The association between recurrent VTE and
      a previously developed risk score, baseline values of the biomarkers, and
      individual relative changes from baseline were assessed. RESULTS: We enrolled 117
      cancer patients (22% lung, 21% colorectal, 9% breast) with a mean age of 63
      years; 62% had metastatic cancer. Eleven patients (9.4%) developed recurrent VTE,
      including two cases of fatal pulmonary embolism. VTE recurrence rates were 7.8%
      (95% CI, 3.1-18) in patients with a risk score of <=0 points compared to 11% (95%
      CI, 5.2-20) for those with a score of >=1 point (hazard ratio 1.3; 95% CI, 0.39
      4.5). Baseline P-selectin levels but not D-dimer levels were significantly
      associated with a high risk of recurrence; the risk was four-fold higher in
      patients with elevated P-selectin levels than in those with normal levels (hazard
      ratio 4.0; 95% CI, 1.1-14). Changes in biomarker levels during treatment were not
      associated with recurrent VTE. CONCLUSION: Baseline P-selectin but not D-dimer
      levels predict recurrent VTE and may be a valuable addition to clinical
      prediction rules to select patients for more intensive therapy or closer
      observation.

PMID- 29353683
TI  - Diagnosing upper extremity deep vein thrombosis with non-contrast-enhanced
      Magnetic Resonance Direct Thrombus Imaging: A pilot study.
AB  - Diagnosing upper extremity deep vein thrombosis (UEDVT) can be challenging.
      Compression ultrasonography is often inconclusive because of overlying anatomic
      structures that hamper compressing veins. Contrast venography is invasive and has
      a risk of contrast allergy. Magnetic Resonance Direct Thrombus Imaging (MRDTI)
      and Three Dimensional Turbo Spin-echo Spectral Attenuated Inversion Recovery (3D
      TSE-SPAIR) are both non-contrast-enhanced Magnetic Resonance Imaging (MRI)
      sequences that can visualize a thrombus directly by the visualization of
      methemoglobin, which is formed in a fresh blood clot. MRDTI has been proven to be
      accurate in diagnosing deep venous thrombosis (DVT) of the leg. The primary aim
      of this pilot study was to test the feasibility of diagnosing UEDVT with these
      MRI techniques. MRDTI and 3D TSE-SPAIR were performed in 3 pilot patients who
      were already diagnosed with UEDVT by ultrasonography or contrast venography. In
      all patients, UEDVT diagnosis could be confirmed by MRDTI and 3D TSE-SPAIR in all
      vein segments. In conclusion, this study showed that non-contrast MRDTI and 3D
      TSE-SPAIR sequences may be feasible tests to diagnose UEDVT. However diagnostic
      accuracy and management studies have to be performed before these techniques can
      be routinely used in clinical practice.

PMID- 29353684
TI  - Fatal acute disseminated intravascular coagulation as presentation of advanced
      ALK-positive non-small cell lung cancer: Does oncogene addiction matter?

PMID- 29353685
TI  - Secondary and sucrose metabolism regulated by different light quality
      combinations involved in melon tolerance to powdery mildew.
AB  - We evaluated the effect of different light combinations on powdery mildew
      resistance and growth of melon seedlings. Light-emitting diodes were used as the
      light source and there were five light combinations: white light (420-680 nm);
      blue light (460 nm); red light (635 nm); RB31 (ratio of red and blue light, 3:
      1); and RB71 (ratio of red and blue light, 7: 1). Compared with other treatments,
      blue light significantly decreased the incidence of powdery mildew in leaves of
      melon seedlings. Under blue light, H2O2 showed higher accumulation, and the
      content of phenolics, flavonoid and tannins, as well as expression of the genes
      involved in synthesis of these substances, significantly increased compared with
      other treatments before and after infection. Lignin content and expression of the
      genes related to its synthesis were also induced by blue light before infection.
      Melon irradiated with RB31 light showed the best growth parameters. Compared with
      white light, red light and RB71, RB31 showed higher accumulation of lignin and
      lower incidence of powdery mildew. We conclude that blue light increases melon
      resistance to powdery mildew, which is dependent on the induction of secondary
      metabolism that may be related to H2O2 accumulation before infection. Induction
      of tolerance of melon seeds to powdery mildew by RB31 is due to higher levels of
      sucrose metabolism and accumulation of lignin.

PMID- 29353686
TI  - 5-aminolevulinic acid improves salt tolerance mediated by regulation of
      tetrapyrrole and proline metabolism in Brassica napus L. seedlings under NaCl
      stress.
AB  - 5-aminolevulinic acid (ALA), a key biosynthetic precursor of tetrapyrroles, is
      vital for plant growth and adaptation to stress environments. Although exogenous
      ALA could enhance photosynthesis and biomass accumulation in plants under stress
      conditions, the underlying physiological and molecular mechanisms governed by ALA
      in promoting salt tolerance in Brassica napus L. are not yet clearly understood.
      In the present study, exogenous ALA with the concentration of 30 mg L-1 was
      applied to the leaves of B. napus seedlings subjected to 200 mM NaCl. The results
      showed that NaCl stress decreased the photosynthesis, biomass accumulation, and
      levels of chlorophyll and heme with the reduction of the concentrations of
      intermediates including ALA, protoporphyrin IX (Proto IX), Mg-Proto IX, and
      Pchlide in the tetrapyrrole (chlorophyll and heme) biosynthetic pathway. The
      transcript levels of genes encoding ALA-associated enzymes and genes encoding Mg
      chelatase in the chlorophyll biosynthetic branch were down-regulated, while the
      expression levels of genes encoding Fe-chelatase in the heme branch were not
      significantly altered by NaCl stress. Foliar application with ALA enhanced the
      aboveground biomass, net photosynthetic rate, activities of antioxidant enzymes,
      accumulation of chlorophyll and heme, and concentrations of intermediates related
      to chlorophyll and heme biosynthesis in B. napus under 200 mM NaCl. The
      expression of most genes mentioned above remained constant in ALA-treated plants
      in comparison with non-ALA-treated plants under NaCl stress. Additionally,
      exogenous ALA synchronously induced the proline concentration and up-regulated
      the expression of genes P5CS and ProDH encoding proline metabolic enzymes in the
      NaCl treatment. These findings suggested that ALA improved salt tolerance through
      promoting the accumulation of chlorophyll and heme resulting from the increase of
      intermediate levels in the tetrapyrrole biosynthetic pathway, along with
      enhancing the proline accumulation in B. napus.

PMID- 29353687
TI  - Th17 immune responses in Brazilian dyslipidemic patients with atherosclerosis.

PMID- 29353688
TI  - Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early
      mortality in decompensated liver cirrhosis.
AB  - BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic
      inflammation. However, its predictive utility of 30-day mortality remains elusive
      in decompensated cirrhotics. AIMS: We aimed to combine NLR and other variables
      associated with early mortality of cirrhotics with acute insults in to a
      predictive nomogram. METHODS: We retrospectively analyzed 352 decompensated
      cirrhotics. The 30-day mortality was regarded as primary outcome. Multivariate
      Cox analysis was performed, and a NLR-based nomogram was developed. The
      performance of nomogram was determined in terms of its calibration,
      discrimination and clinical usefulness. Serum cytokines were evaluated by
      Milliplex cytokine assay. RESULTS: On multiple analysis, independent factors for
      early mortality were albumin, MELD and NLR, which were all selected into the
      nomogram. The nomogram showed good discrimination, with a concordance index of
      0.88. Calibration of the nomogram predicted survival corresponding optimally with
      the actual outcomes. Decision curve analysis indicated our nomogram was useful in
      clinical practice. Among circulating cytokines we investigated, IL-6 and IL-8
      were substantially elevated in cirrhotics compared to healthy subjects. High NLR
      was positively correlated with the expression of IL-6 and IL-8. CONCLUSION: The
      proposed nomogram incorporating NLR offered an individualized predictive tool for
      30-day mortality in decompensated cirrhotics. The escalating value of NLR likely
      implicated excessive inflammatory response.

PMID- 29353689
TI  - Neonatal outcomes with water birth: A systematic review and meta-analysis.

PMID- 29353690
TI  - A quantitative longitudinal study to explore factors which influence maternal
      self-efficacy among Chinese primiparous women during the initial postpartum
      period.
AB  - BACKGROUND: parenting during infancy is highly problematic for Chinese
      primiparous women. As an important determinant of good parenting, maternal self
      efficacy (MSE) should be paid more attention by researchers. At present, the
      limitations of previous research about MSE during infancy are that the factors
      which influence MSE remained poorly explored, there were few studies with Chinese
      women, and the studies did not consider the effect of different cultures.
      OBJECTIVES: to explore factors which influence MSE in primiparous women in China
      in the first three months postnatally. METHODS: a quantitative longitudinal study
      using questionnaires was conducted. In total, 420 Chinese primiparous women were
      recruited in obstetric wards at three hospitals in Xiamen City, Fujian Province
      of China. Initial baseline questionnaires to measure socio-demographic and
      clinical characteristics were distributed to participants face-to-face by the
      researcher on the postnatal ward at three days postnatally. Follow-up
      questionnaires at six and 12 weeks postnatally were sent via e-mail by the
      researcher to participants, including the Self-efficacy in Infant Care Scale
      (SICS), the Edinburgh Postnatal Depression Scale (EPDS) and the Postpartum Social
      Support Scale (PSSS) to measure MSE, postnatal depression symptoms and social
      support, respectively. These were returned by participants via e-mail.
      Quantitative data were analysed using SPSS. RESULTS: the variables: social
      support, women's satisfaction with 'Doing the month', postnatal depression,
      maternal education, baby health, and maternal occupation had an influence on MSE
      at six weeks postnatally (Adjusted R2 = 0.510, F = 46.084, P<0.01); and the
      variables: postnatal depression, social support, baby health, women's
      satisfaction with 'Doing the month', and baby fussiness were the factors
      influencing MSE at 12 weeks postnatally (Adjusted R2 = 0.485, F = 41.082,
      P<0.01). CONCLUSIONS: obstetric nurses and women's family members need to be
      aware of the significant contribution of social support, women's satisfaction
      with 'Doing the month' in positively influencing primiparous women's MSE, and the
      significant effect of postnatal depression symptoms in negatively impacting on
      first-time mothers' MSE; they should pay more attention to primiparous women with
      less education, unemployed mothers, women with unskilled occupations, women with
      an unhealthy baby, and women with a baby with a difficult temperament to improve
      their comparatively lower MSE levels during the initial postnatal period.

PMID- 29353691
TI  - Barriers to addressing perinatal mental health issues in midwifery settings.
AB  - BACKGROUND: poor perinatal mental health is linked to various adverse pregnancy
      and child outcomes. Despite having a holistic philosophy of care, similar to
      other maternity care settings, perinatal mental health issues often remain under
      diagnosed and untreated in midwifery settings. AIM: to determine midwives'
      perceived barriers to the screening, referral, and management of perinatal mental
      health issues. DESIGN: integrative review. METHODS: the following databases were
      searched: MEDLINE, CINAHL, EMBASE, and PsycINFO. We included qualitative,
      quantitative, and mixed methods studies published in a peer-reviewed journal in
      English. Two reviewers independently extracted data and subsequently integrated
      the extracted data into a single data matrix. The data matrix was compared
      iteratively across primary data sources to identify themes and sub-themes. The
      identified barriers to screening, management and referrals were subsequently
      categorized into provider-level and system-level barriers. The relevance and
      methodological quality of the included studies were evaluated using appropriate
      checklists. FINDINGS: three hundreds and fifty six articles were retrieved.
      Twenty studies met the inclusion criteria and were included. Insufficient/lack of
      training, lack of clarity regarding the scope of practice and time constraints
      were common provider level barriers across various stages of addressing mental
      health issues from identification to management. The system-level barriers were
      more complex and diverse and included unclear pathways and unlinked services,
      lack of local guidelines or policies, continuity of care, structured office
      procedures, clinical support and supervision and accessible educational
      resources, scarcity of available referral resources, complex bureaucratic
      processes and challenges related to expansion of the scope of practice.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: training, expansion of the scope of
      practice and collaborative care are central for successful screening, management
      and appropriate and timely referrals of perinatal mental health issues. An
      integrative model of care may address fragmentation in perinatal mental health
      services and enable a holistic midwifery care.

PMID- 29353692
TI  - The use of drama within midwifery education to facilitate the understanding of
      professional behaviour and values.
AB  - OBJECTIVE: to develop student midwife understanding of professional values and
      the application of these in clinical practice, prior to commencing their first
      clinical placement. DESIGN: an action research project. SETTING: a Simulation
      Suite environment within a University setting. PARTICIPANTS: 6 year 3 drama
      students and a cohort of 36 midwifery students. FINDINGS: the students were
      supportive of the idea of collaborative projects as this permitted the
      facilitation of student understanding of key professional values and their
      application in the clinical setting. KEY CONCLUSIONS: the students felt that the
      move away from a didactic approach to learning and teaching towards a more
      experiential model of teaching, enabled a more in depth reflection on the
      importance of professional standards and behaviour when providing care to
      pregnant women.

PMID- 29353693
TI  - Multiscale molecular dynamics simulations of lipid interactions with P
      glycoprotein in a complex membrane.
AB  - P-glycoprotein (P-gp) can transport a wide range of very different hydrophobic
      organic molecules across the membrane. Its ability to extrude molecules from the
      cell creates delivery problems for drugs that target proteins in the central
      nervous system (CNS) and also causes drug-resistance in many forms of cancer.
      Whether a drug will be susceptible to export by P-gp is difficult to predict and
      currently this is usually assessed with empirical and/or animal models. Thus,
      there is a need to better understand how P-gp works at the molecular level in
      order to fulfil the 3Rs: Refinement, reduction and replacement of animals in
      research. As structural information increasingly becomes available, our
      understanding at the molecular level improves. Proteins like P-gp are however
      very dynamic entities and thus one of the most appropriate ways to study them is
      with molecular dynamics simulations, especially as this can capture the influence
      of the surrounding environment. Recent parameterization developments have meant
      that it is now possible to simulate lipid bilayers that more closely resemble in
      vivo membranes in terms of their composition. In this report we construct a
      complex lipid bilayer that mimics the composition of brain epithelial cells and
      examine the interactions of it with P-gp. We find that the negatively charged
      phosphatidylserine lipids in the inner leaflet of the membrane tend to form an
      annulus around P-gp. We also observed the interaction of cholesterol with three
      distinct areas of the P-gp. Potential of mean force (PMF) calculations suggest
      that a crevice between transmembrane helices 10 and 12 has particularly
      favourable interaction energy for cholesterol.

PMID- 29353694
TI  - Targeting Candida spp. to develop antifungal agents.
AB  - Invasive fungal infections are a complex challenge throughout the world because
      of their high incidence, mainly in critically ill patients, and high mortality
      rates. The antifungal agents currently available are limited; thus, there is a
      need for the rapid development of new drugs. In silico methods are a modern
      strategy to explore interactions between new compounds and specific fungal
      targets, but they depend on precise genetic information. Here, we discuss the
      main Candida spp. target genes, including information about null mutants,
      virulence, cytolocalization, co-regulatory genes, and compounds that are related
      to protein expression. These data will provide a basis for the future in silico
      development of antifungal drugs.

PMID- 29353695
TI  - Experimental rheological procedure adapted to pasty dewatered sludge up to 45 %
      dry matter.
AB  - Wastewater sludge are characterized by complex rheological properties, strongly
      dependent on solids concentration and temperature. These properties are required
      for process hydrodynamic modelling but their correct measurement is often
      challenging at high solids concentrations. This is especially true to model the
      hydrodynamic of dewatered sludge during drying process where solids content (TS)
      increases with residence time. Indeed, until now, the literature mostly focused
      on the rheological characterization of sludge at low and moderate TS (between 4
      and 8%). Limited attention was paid to pasty and highly concentrated sludge
      mainly because of the difficulties to carry out the measurements. Results
      reproducibility appeared to be poor and thus may not be always fully
      representative of the effective material properties. This work demonstrates that
      reproducible results can be obtained by controlling cracks and fractures which
      always take place in classical rotational rheometry. In that purpose, a well
      controlled experimental procedure has been developed, allowing the exact
      determination of the surface effectively sheared. This surface is calculated by
      scattering a classical stress sweep with measurements at a reference strain
      value. The implementation of this procedure allows the correct determination of
      solid-like characteristics from 20 to 45% TS but also shows that pasty and highly
      concentrated sludge highlight normal forces caused by dilatancy. Moreover the
      surface correction appears to be independent of TS in the studied range.

PMID- 29353696
TI  - Uptake of pharmaceuticals by sorbent-amended struvite fertilisers recovered from
      human urine and their bioaccumulation in tomato fruit.
AB  - Struvite precipitation is a well-documented method for recovering up to 98% of
      phosphorus from urine, which is one of the main nutrients in fertilizers besides
      nitrogen and potassium. Shortcomings of this process, however, are the low
      nitrogen recovery ratio and the possible uptake of pharmaceuticals from urine. In
      this work, the NH4+ adsorbent materials biochar and zeolite are coupled with
      struvite precipitation to increase the N-recovery of struvite from 5.7% to 9.8%.
      Since nitrogen is one of the main nutrients in fertilisers, this increase is of
      significance for its potential commercial use. In addition, urine is spiked with
      pharmaceuticals to measure the consequential uptake in struvite-based fertilisers
      and crops afterwards. Five fertilisers are prepared by nutrient recovery from
      spiked urine using: (1) struvite crystallisation, (2) struvite crystallisation
      combined with N adsorption on zeolite, (3) struvite crystallisation combined with
      N adsorption on biochar, (4) N adsorption on zeolite without struvite
      crystallisation, and (5) N adsorption on biochar without struvite
      crystallisation. The fertiliser with the highest purity product and the lowest
      uptake of pharmaceuticals was struvite combined with zeolite. Next, the
      contaminated struvite-sorbent fertilisers are tested in a crop trial in which the
      bioaccumulation of pharmaceuticals in edible plant tissue (tomatoes) is measured.
      This bioaccumulation in tomato fruit biomass from each of the spiked fertilisers
      in the crop trial was found to be lower than 0.0003% in all cases, far below the
      acceptable daily intake (ADI) levels (750 kg of dry tomatoes should be consumed
      per day to reach the ADI limit). Consequently, the subsequent risk to human
      health from tomato fruit grown using urine derived struvite-sorbent fertilisers
      is found to be insignificant.

PMID- 29353697
TI  - Strontium adsorption and desorption in wetlands: Role of organic matter
      functional groups and environmental implications.
AB  - Strontium (Sr) is a chemical element that is often used as a tracer in
      hydrogeochemical studies, and is ubiquitously distributed as a radioactive
      contaminant in nuclear sites in the form of strontium-90 (Sr-90). At the
      interface between groundwater and surface water, wetlands possess unique
      hydrogeochemical properties whose impact on Sr transport has not been
      investigated thoroughly. In this study, the adsorption and desorption of Sr was
      investigated on six natural wetland substrates and two mixes of exogenous media
      and wetland sediment: winter and summer wetland sediments, decayed cattails,
      wood, leaf litter, moss, bone charcoal, and clinoptilolite. The composition of
      the organic matter was characterized using carbon-13, solid phase Nuclear
      Magnetic Resonance analysis. The range of the substrates' adsorption coefficients
      obtained could be explained by factors indicative of proteins in the organic
      matter, which were shown to support strong and poorly reversible Sr adsorption.
      In contrast, the proportion of carbohydrates and lignin were found to be
      indicative of lower adsorption coefficients and higher desorption. The
      implications of these results for Sr pollution remediation in wetlands are
      discussed.

PMID- 29353698
TI  - Seasonal pattern of anthropogenic salinization in temperate forested headwater
      streams.
AB  - Salinization of freshwaters by human activities is of growing concern globally.
      Consequences of salt pollution include adverse effects to aquatic biodiversity,
      ecosystem function, human health, and ecosystem services. In headwater streams of
      the temperate forests of eastern USA, elevated specific conductance (SC), a
      surrogate measurement for the major dissolved ions composing salinity, has been
      linked to decreased diversity of aquatic insects. However, such linkages have
      typically been based on limited numbers of SC measurements that do not quantify
      intra-annual variation. Effective management of salinization requires tools to
      accurately monitor and predict salinity while accounting for temporal
      variability. Toward that end, high-frequency SC data were collected within the
      central Appalachian coalfield over 4 years at 25 forested headwater streams
      spanning a gradient of salinity. A sinusoidal periodic function was used to model
      the annual cycle of SC, averaged across years and streams. The resultant model
      revealed that, on average, salinity deviated approximately +/-20% from annual
      mean levels across all years and streams, with minimum SC occurring in late
      winter and peak SC occurring in late summer. The pattern was evident in headwater
      streams influenced by surface coal mining, unmined headwater reference streams
      with low salinity, and larger-order salinized rivers draining the study area. The
      pattern was strongly responsive to varying seasonal dilution as driven by
      catchment evapotranspiration, an effect that was amplified slightly in unmined
      catchments with greater relative forest cover. Evaluation of alternative sampling
      intervals indicated that discrete sampling can approximate the model performance
      afforded by high-frequency data but model error increases rapidly as discrete
      sampling intervals exceed 30 days. This study demonstrates that intra-annual
      variation of salinity in temperate forested headwater streams of Appalachia USA
      follows a natural seasonal pattern, driven by interactive influences on water
      quantity and quality of climate, geology, and terrestrial vegetation. Because
      climatic and vegetation dynamics vary annually in a seasonal, cyclic manner, a
      periodic function can be used to fit a sinusoidal model to the salinity pattern.
      The model framework used here is broadly applicable in systems with streamflow
      dependent chronic salinity stress.

PMID- 29353699
TI  - Near-infrared heat lamp therapeutic effect on paraoxonase 1 and myeloperoxidase
      as potential biomarkers of redox state changes induced by gamma-irradiation in
      albino rats.
AB  - Infrared radiation has a potential therapeutic effect in some diseases. The aim
      of this study was to estimate the therapeutic role of near infrared heat lamp
      (NIRHL) on the variations of the activity of paraoxonase 1 (PON1) and
      myeloperoxidase (MPO), in relation to lipid disorders, associated with oxidative
      stress in rats gamma-irradiated. In addition, study the effect of the duration of
      NIRHL treatment. Animals were divided into six groups. The results revealed that
      irradiated rats treated with NIRHL 20 min/once/day showed positive modulation of
      PON1 and MPO linked to significant improvement of lipid disorders evidenced by
      lower triglycerides, low density lipoprotein cholesterol (LDL-C), oxidized low
      density lipoprotein cholesterol (oxLDL-C) and higher density lipoprotein
      cholesterol (HDL-C) as well as significant amelioration of redox state,
      manifested by markedly increase of glutathione (GSH) content, total antioxidant
      capacity (TAC) associated with a noticeable decrease of pro-inflammatory
      cytokines. (TNF-alpha, IL-1 beta and IL-6), nitric oxide (NO), nitric oxide
      synthase (NOs), malondialdehyde (MDA), compared to irradiated rats. The results
      showed also that the NIRHL treatment for 20 min/twice/day had negative effects on
      the previous parameters and on the behavior of rats such as itching,
      irritability, dyspnea and death in normal as well as, irradiated rats. In
      conclusion, the results in this study show that NIRHL therapy for a short time
      can effectively prevent the lipid disorders induced by radiation through the
      positive modulation mechanism of PON1 and MPO enzymes and improvement of
      oxidative stress.

PMID- 29353700
TI  - Developmental variation during seed germination and biochemical responses of
      Brassica rapa exposed to various colored lights.
AB  - Light acting as elicitor or stress inducer, it plays a pivotal role in all
      developmental processes of plant providing necessary building blocks for growth
      and primary and secondary metabolites production. The main objective of the
      current study was to investigate the individual effect of colored lights on
      developmental processes and production of polyphenolics contents in Brassica
      rapa. In this study, the red and white lights (control) were found to be the most
      effective sources for seed germination (91%) in Brassica rapa. Similarly, red
      light enhanced radicle growth (102 mm), while green light suppressed radicle
      growth (60 mm) as compared to control (67 mm). The red light also promoted the
      plumule growth (50 mm) as compared to control (37 mm). The maximum biomass gain
      (67 mg) was observed under red light as compared to control (55 mg). Currently,
      the maximum total phenolics content (9.49 mg/g-DW) and phenolics production
      (379.616 mg/L) was observed under the influence of blue lights as compared to
      control (0.23 mg/g-DW and 8.91 mg/L). Similarly, the blue lights also enhanced
      the biosynthesis of total flavonoids content (2.2611 mg/g-DW) and flavonoids
      production (90.44 mg/L) as compared to control (0.0318 md/g-DW and 0.8268 mg/L).
      The current results represents that red and blue lights are the most effective
      sources for plantlets development and production of polyphenolics content in
      Brassica rapa.

PMID- 29353701
TI  - Photobiomodulation at 660nm stimulates proliferation and migration of diabetic
      wounded cells via the expression of epidermal growth factor and the JAK/STAT
      pathway.
AB  - Photobiomodulation (PBM) modulates cellular processes to enhance diabetic wound
      healing. The photon energy activates wounded cells to proliferate and migrate.
      However, the signalling pathways responsible for these observations remain
      unknown. This study aimed to determine if PBM stimulates cellular proliferation
      and migration via the expression of epidermal growth factor (EGF) and activation
      of the Janus kinase/Signal transducer and activators of transcription (JAK/STAT)
      signalling pathway. Normal, wounded, diabetic and diabetic wounded cell models
      were exposed to PBM at a wavelength of 660nm and fluence of 5J/cm2 and incubated
      for 48h. Non-irradiated cells (0J/cm2) and cells exposed to exogenous EGF (rh
      EGF) served as controls. Cellular migration was determined microscopically at 0,
      24 and 48h. Flow cytometry (BrdU) was used to determine cell proliferation, while
      the Trypan blue exclusion assay and adenosine triphosphate (ATP) luminescence was
      used to determine cell viability. The enzyme linked immunosorbent assay (ELISA)
      was used to analyse EGF expressed in the culture media, and phosphorylated (p-)
      EGF receptor (p-EGFR), p-JAK2, p-STAT1 and p-STAT5 in cells. Irradiated diabetic
      wounded cells showed a significant increase in EGF, and activation of its
      receptor (p-EGFR) and JAK/STAT (p-JAK2, p-STAT1 and p-STAT5). PBM at 660nm and
      5J/cm2 is able to modulate cellular autocrine signalling, particularly the
      EGF/EGFR loop leading to activation of the JAK/STAT pathway which in turn
      stimulates cell proliferation and migration.

PMID- 29353702
TI  - Enzyme-mediated photoinactivation of Enterococcus faecalis using Rose Bengal
      acetate.
AB  - Rose Bengal-acetate (RB-Ac) is a pro-photosensitizer claimed to diffuse into
      target cells, where the acetate groups are hydrolyzed and the photosensitizing
      properties of Rose Bengal (RB) are restored. Despite promising results on tumor
      cells, the interaction of RB-Ac with bacteria has never been investigated. This
      study aimed to assess the interaction of RB-Ac with Enterococcus faecalis and to
      evaluate its potential use in antimicrobial photodynamic therapy (aPDT).
      Spectrofluorometry was used to assess the ability of E. faecalis to hydrolyze the
      RB-Ac compound. Fluorescence microscopy was employed to observe the distribution
      and to evaluate the cellular uptake of the RB produced. The antibacterial
      efficiency of RB-Ac-mediated aPDT was assessed by flow cytometry in combination
      with the LIVE/DEAD(r) staining. Results showed that RB-Ac was successfully
      hydrolyzed in the presence of E. faecalis cells. The RB produced appeared to
      incorporate the membrane of bacteria. Higher concentrations of RB-Ac resulted in
      higher incorporation of RB. The blue-light irradiation of RB-Ac-treated samples
      significantly reduced bacterial viability. Less than 0.01% of E. faecalis
      survived after incubation with 200 MUM RB-Ac during 900 min and blue-light
      activation. The current report indicates that E. faecalis cells can hydrolyze the
      RB-Ac compound to produce active RB. The use of RB-Ac did not appear to allow
      cytoplasmic internalization of the RB produced, which rather incorporated the
      membrane bilayers of E. faecalis. The use of RB-Ac did not provide additional
      advantages over RB in terms of PS localization. Nonetheless, sufficient RB was
      produced and incorporated into the membranes of bacteria to elicit effective
      aPDT.

PMID- 29353703
TI  - Generation of an induced pluripotent stem cell line (CSC-44) from a Parkinson's
      disease patient carrying a compound heterozygous mutation (c.823C>T and EX6 del)
      in the PARK2 gene.
AB  - Mutations in the PARK2 gene, which encodes PARKIN, are the most frequent cause of
      autosomal recessive Parkinson's disease (PD). We report the generation of an
      induced pluripotent stem cell (iPSC) line from a 78-year-old patient carrying a
      compound heterozygous mutation (c.823C>T and EX6del) in the PARK2 gene. Skin
      fibroblasts were reprogrammed using the non-integrating Sendai virus technology
      to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line CSC-44
      exhibits expression of common pluripotency markers, in vitro differentiation into
      the three germ layers and normal karyotype. This iPSC line can be used to explore
      the association between PARK2 mutations and PD.

PMID- 29353704
TI  - Prediction of pH and aw of pork meat by a thermodynamic model: New developments.
AB  - To ensure continuous innovations, food industries need tools which enable to
      predict physical-properties of food during a change of process or recipe. In this
      work, a thermodynamic model is suggested to predict pH and water activity of pork
      meat in presence of different additives such as salts or organic acids used in
      food industry. The predictions of pH and aw are satisfactory in a wide prediction
      domain, with a good accuracy. In add, a neural network mimetic of thermodynamic
      model is developed in order to facilitate the use of thermodynamic model and
      reduce calculation time.

PMID- 29353705
TI  - Association between SCN1A gene polymorphisms and drug resistant epilepsy in
      pediatric patients.
AB  - PURPOSE: "Single Nucleotide Polymorphisms (SNPs)" could be an important
      explanation of drug resistance in epilepsy. The aim of this study was to
      investigate if genetic polymorphisms (SNPs) of the SCN1A gene could influence the
      response to anti - epileptic drugs (AED) and if they could predispose to a drug
      resistant epilepsy in pediatric patients. METHODS: We investigated SNPs in exon
      and intronic regions of the SCN1A gene in a sample of 120 pediatric patients, in
      both drug-resistant and drug-responsive patients. Association between
      polymorphisms and refractory epilepsy were investigated by comparing SNPs in exon
      and intronic regions between the two groups. The genotypes of each intronic
      polymorphism in the drug-resistant group was analyzed. Odds ratios and confidence
      intervals were calculated. RESULTS: None of the SNPs identified in exons of the
      SCN1A gene were associated with drug-resistance. In the intronic regions, a
      statistically significant difference was found in the prevalence of three
      polymorphisms was found between the two patient groups (rs6730344A/C,
      rs6732655A/T, rs10167228A/T). The analysis of the genotypes of each intronic
      polymorphism in the drug-resistant group revealed that the AA and AT genotypes
      for the rs1962842 polymorphism are associated with an increased risk of
      developing drug resistance compared to TT genotype. CONCLUSION: The intronic
      rs6730344, rs6732655 and rs10167228 polymorphisms of the SCN1A gene are a
      potential risk factors for drug resistance. AA e AT genotype of the rs1962842
      intronic polymorphism also emerged as a risk factor in the drug resistant group.
      Therefore, polymorphisms of the SCN1A gene could play a role in the response to
      AED in patients with drug-resistant epilepsy, with important implications for
      clinical practice.

PMID- 29353706
TI  - Children's early understanding of number predicts their later problem-solving
      sophistication in addition.
AB  - Previous studies suggest that the sophistication of the strategies children use
      to solve arithmetic problems is related to a more basic understanding of number,
      but they have not examined the relation between number knowledge in preschool and
      strategy choices at school entry. Accordingly, the symbolic and nonsymbolic
      quantitative knowledge of 134 children (65 boys) was assessed at the beginning of
      preschool and in kindergarten, and the sophistication of the strategies they used
      to solve addition problems was assessed at the beginning of first grade. Using a
      combination of Bayes and standard regression models, we found that children's
      understanding of the cardinal value of number words at the beginning of preschool
      predicted the sophistication of their strategy choices 3 years later, controlling
      for other factors. The relation between children's early understanding of
      cardinality and their strategy choices was mediated by their symbolic and
      nonsymbolic quantitative knowledge in kindergarten. The results suggest that
      sophisticated strategy choices emerge from children's developing understanding of
      the relations among numbers, in keeping with the overlapping waves model.

PMID- 29353707
TI  - Attentional rather than sensory differences characterize auditory processing in
      Williams syndrome.
AB  - Individuals with Williams Syndrome (WS) exhibit an atypical auditory profile.
      Across two experiments, we used event-related potentials (ERPs) in a three
      stimulus auditory oddball task to examine early sensory (P1, N1, P2) and later
      cognitive (P3a, P3b) stages of cortical auditory processing in adults with WS and
      age-matched typical peers. In Study 1, piano chords served as standard, target,
      and novel stimuli; whereas, in Study 2, a variety of non-piano sounds comprised
      the novel stimuli. Across both experiments, there were no group differences in
      the earliest stages of sensory encoding (P1, N1), along with evidence for
      atypically large P2 responses in participants with WS. Persons with WS exhibited
      larger than typical P3a responses when the novel stimuli were perceptually
      distinct from the standard and the target stimuli (Study 2), but not when task
      relevant and -irrelevant stimuli were perceptually similar (Study 1). Further,
      the WS group demonstrated reduced goal-directed attention (attenuated P3b
      response). These group differences in ERPs were not directly related to IQ. Our
      results in the context of an active discrimination task point to a more complex
      profile of auditory processing in persons with WS than previously reported, with
      group differences emerging during the later stages of stimulus categorization and
      evaluation, but not within early stimulus detection and feature encoding.

PMID- 29353708
TI  - Adolescents' experiences of living with sickle cell disease: An integrative
      narrative review of the literature.
AB  - BACKGROUND: Sickle Cell Disease is the commonest monogenic haemoglobinopathy
      worldwide. Living with a long-term condition such as sickle cell disease during
      adolescence constitutes a significant challenge for the key stakeholders due to
      the combined effects of chronic illness and adolescent development. For
      adolescents with sickle cell disease to be cared for and supported appropriately
      and effectively, it is crucial that health professionals have a comprehensive
      knowledge and understanding of how adolescents experience living with the
      condition. While there is developing literature about how adolescent's experience
      sickle cell disease, this body of research has not been critically reviewed and
      synthesised. OBJECTIVE: To identify, critically appraise and synthesise primary
      research exploring adolescents' experiences of living with sickle cell disease to
      make recommendations for practice and research. DESIGN: Integrative narrative
      review. DATA SOURCES: A systematic search of 10 electronic databases and key
      journals was conducted to identify studies from the inception of databases to
      September 2016. REVIEW METHOD: Inclusion criteria: adolescents with sickle cell
      disease aged 12-19 years, primary data on adolescents' own perspectives, and
      published in English. Data were extracted on study contexts, methodology/design,
      theoretical constructs, participants, and key findings. Findings from included
      studies were synthesised using the integrative narrative approach. Additionally,
      the methodological quality of studies was assessed using the Hawker et al. (2002)
      appraisal checklist. RESULTS: 683 studies were identified, of which 40 fulfilled
      the inclusion criteria. Nine broad themes emerged: knowledge and understanding of
      the condition, symptom experiences, self-management, attitude to treatment,
      healthcare experiences, social relationships, difference and striving for
      normality, school experiences, and emotional well-being and coping. Majority of
      the studies were of moderate quality methodologically. Quality assessment
      demonstrated a high risk of bias in three studies. CONCLUSIONS: Sickle cell
      disease impacts on multiple facets of an adolescent's life. While there are
      similarities in the experience of living with sickle cell disease and living with
      other chronic illnesses, there are essential differences in relationship dynamics
      and healthcare experience. The adolescents expressed less confidence in generic
      healthcare providers. The review highlights areas relating to symptom management
      and health service provision that has been under-researched and need further
      exploration to understand adolescents' experiences and their support needs fully.
      Nursing care and research should focus more on adolescents' developmental
      wellbeing, promote peer support network among adolescents with the condition and
      with adolescents with other chronic illnesses and collaborate with adolescents to
      ensure service development are developmentally and culturally appropriate.

PMID- 29353709
TI  - The role of telenursing in the management of Diabetes Type 1: A randomized
      controlled trial.
AB  - BACKGROUND: Diabetes Mellitus type 1 (T1DM) is a chronic disease that requires
      patients' self-monitoring and self-management to achieve glucose targets and
      prevent complications. Telenursing implicates technology in the interaction of a
      specialized nurse with patients with chronic diseases in order to provide
      personalized care and support. OBJECTIVE: To evaluate the effect of telenursing
      on T1DM patients' compliance with glucose self-monitoring and glycemic control.
      DESIGN: Randomized controlled study. SETTINGS: Outpatient Department of Diabetes,
      Endocrinology and Metabolism of a University Hospital in Northern Greece.
      METHODS: Ninety-four T1DM patients were recruited and randomized in two groups by
      a random number generator. The intervention group (N = 48) was provided with
      telenursing services. A specialized nurse made a weekly contact via telephone
      motivating patients to frequently measure blood glucose and adopt a healthy
      lifestyle. The control group (N = 46) received standard diabetes advice and care
      in the clinic. The primary outcome was the effect of the intervention in glucose
      control and glucose variability. The secondary outcome was the effect on
      frequency of self-monitoring. SPSS 20.0 was used for data analysis. RESULTS: The
      two groups did not differ in age, sex, physical activity or initial HbA1c. In the
      intervention group, blood glucose significantly decreased at the end of the study
      in all predefined measurements, compared to control group: morning (93.18 +/-
      13.30 mg/dl vs. 105.17 +/- 13.74 mg/dl, p < 0.005), pre-prandial (114.76 +/- 9.54
      mg/dl vs. 120.84 +/- 4.05 mg/dl, p < 0.005), post-prandial (193.35 +/- 25.36
      mg/dl vs. 207.84 +/- 18.80 mg/dl, p < 0.005), and HbA1c decreased significantly
      over time in the intervention group (8.3 +/- 0.6% at the beginning of the study
      vs. 7.8 +/- 1% at the end of the study, p = 0.03). In the intervention group
      there were also fewer omitted glucose measurements than in the control group.
      CONCLUSIONS: Patients in the intervention group achieved better glucose control
      and more frequent self-monitoring than patients in routine care in the clinic.
      The findings of our study indicate that telenursing can motivate T1DM patients to
      better control their disease.

PMID- 29353710
TI  - Prevalence and predictors of difficulty accessing the mouths of intubated
      critically ill adults to deliver oral care: An observational study.
AB  - BACKGROUND: Oral care of intubated patients is essential to the prevention of
      infection and patient discomfort. However, barriers to oral access and delivery
      of oral care have received little attention. OBJECTIVE: To determine prevalence
      and predictors of oral access difficulty. DESIGN: A prospective, observational,
      multi-center study. SETTINGS: Four intensive care units in Toronto, Canada.
      PARTICIPANTS: Adult patients orally intubated for >=48 h. METHODS: We screened
      consecutive admissions once a week to identify eligible participants. We observed
      each patient and asked the patient's nurse about presence or absence of
      difficulty accessing the mouth to deliver oral care across three categories: (1)
      visualizing inside the mouth; (2) obtaining patient cooperation, or (3) inserting
      instruments for delivery of oral care. We asked nurses to identify presence of
      patient behaviors contributing to oral access difficulty and perceived level of
      difficulty on a Likert response scale. We examined patient and treatment
      characteristics associated with extreme difficulty (i.e., difficulty in all 3
      categories) using a generalized estimating equation regression model. RESULTS: A
      total of 428 patients were observed, 58% admitted with a medical diagnosis. More
      than half (57%) had >=2 oral devices up to maximum of 4. Oral care difficulty was
      identified in 83% of patients and rated as moderate to high for 217 (51%).
      Difficulty concerned visibility (74%), patient cooperation (55%), and space to
      insert instruments (53%). Patient behaviors contributing difficulty included
      coughing/gagging (60%), mouth closing (49%), biting (45%) and localizing (27%)
      during care. Variables associated with extreme difficulty included neurological
      (OR 1.92, 95% CI 1.42-2.60) or trauma admission (OR 1.83, 95% CI 1.16-2.89), lack
      of pain assessment or treatment in the 4 h prior to oral care (OR 1.43, 95% CI
      1.14-1.80), more oral devices (OR 1.40, 95% CI 1.05-1.87), and duration of
      intubation (OR 1.05, 95% CI 1.01-1.10). Absence of documented agitation in the 4
      h prior to oral care was associated with less difficulty (OR 0.68, 95% CI 0.54
      0.86). CONCLUSIONS: Oral care is complex and difficulties are experienced in a
      vast majority of intubated patients. Some difficulties are amenable to correction
      such as pain management.

PMID- 29353711
TI  - Problems experienced by informal caregivers of individuals with heart failure: An
      integrative review.
AB  - OBJECTIVES: The purpose of this review was to examine and synthesize recent
      literature regarding problems experienced by informal caregivers when providing
      care for individuals with heart failure in the home. DESIGN: Integrative
      literature review. DATA SOURCES: A review of current empirical literature was
      conducted utilizing PubMed, CINAHL, Embase, Sociological Abstracts, Social
      Sciences Full Text, PsycARTICLES, PsycINFO, Health Source: Nursing/Academic
      Edition, and Cochrane computerized databases. 19 qualitative, 16 quantitative,
      and 2 mixed methods studies met the inclusion criteria for review. REVIEW
      METHODS: Computerized databases were searched for a combination of subject terms
      (i.e., MeSH) and keywords related to informal caregivers, problems, and heart
      failure. The title and abstract of identified articles and reference lists were
      reviewed. Studies were included if they were published in English between January
      2000 and December 2016 and examined problems experienced by informal caregivers
      in providing care for individuals with heart failure in the home. Studies were
      excluded if not written in English or if elements of caregiving in heart failure
      were not present in the title, abstract, or text. Unpublished and duplicate
      empirical literature as well as articles related to specific end-stage heart
      failure populations also were excluded. Methodology described by Cooper and
      others for integrative reviews of quantitative and qualitative research was used.
      Quality appraisal of the included studies was evaluated using the Joanna Briggs
      Institute critical appraisal tools for cross-sectional quantitative and
      qualitative studies. RESULTS: Informal caregivers experienced four key problems
      when providing care for individuals with heart failure in the home, including
      performing multifaceted activities and roles that evolve around daily heart
      failure demands; maintaining caregiver physical, emotional, social, spiritual,
      and financial well-being; having insufficient caregiver support; and performing
      caregiving with uncertainty and inadequate knowledge. CONCLUSIONS: Informal
      caregivers of individuals with heart failure experience complex problems in the
      home when providing care which impact all aspects of their lives. Incorporating
      advice from informal caregivers of individuals with heart failure will assist in
      the development of interventions to reduce negative caregiver outcomes. Given the
      complex roles in caring for individuals with heart failure, multicomponent
      interventions are potentially promising in assisting informal caregivers in
      performing these roles.

PMID- 29353712
TI  - Cost-utility of collaborative nurse-led self-management support for primary care
      patients with anxiety, depressive or somatic symptoms: A cluster-randomized
      controlled trial (the SMADS trial).
AB  - BACKGROUND: Anxiety, depressive and somatoform disorders are highly prevalent and
      cause a huge economic burden. A nurse-led collaborative care intervention has
      been set up in order to improve self-management of patients with these mental
      disorders in primary care in Hamburg, Germany. The aim of this study was to
      determine the cost-utility of this nurse-led intervention from the health care
      payer perspective. METHODS: This analysis was part of a 12-month cluster
      randomized controlled trial aiming to increase perceived self-efficacy of primary
      care patients with anxiety, depressive or somatic symptoms by collaborative nurse
      led self-management support compared with routine care. A cost-effectiveness
      analysis using quality-adjusted life years was performed. Net-monetary benefit
      regressions adjusted for baseline differences for different willingness-to-pay
      thresholds were conducted and cost-effectiveness acceptability curves were
      constructed. RESULTS: In total, n = 325 patients (intervention group: n = 134;
      control group: n = 191) with a mean age of 40 from 20 primary care practices were
      included in the analysis. The adjusted differences in quality-adjusted life years
      and mean total costs between intervention group and control group were +0.02 and
      +?1145, respectively. Neither of the two differences was statistically
      significant. The probability for cost-effectiveness of the complex nurse-led
      intervention was 49% for a willingness-to-pay of ?50,000 per additional quality
      adjusted life year. The probability for cost-effectiveness did not exceed 65%,
      independent of the willingness-to-pay. CONCLUSION: The complex nurse-led
      intervention promoting self-management for primary care patients with anxiety,
      depressive or somatic symptoms did not prove to be cost-effective relative to
      routine care from a health care payer perspective.

PMID- 29353713
TI  - Social media use profile, social skills, and nurse-patient interaction among
      Registered Nurses in tertiary hospitals: A structural equation model analysis.
AB  - BACKGROUND: Social media has become increasingly important over the past decades
      and has been integrated in various environments, including the healthcare
      setting. Yet, the influence of social media use on the social skills and nurse
      patient interaction of nurses is an area in nursing that requires further
      studies. This study determined the interrelationships among social media use
      profile, social skills, and nurse-patient interaction of Registered Nurses in
      tertiary hospitals. METHODS: Employing structural equation modeling, a
      descriptive-correlational study was conducted among 212 consecutively-selected
      nurses from two tertiary hospitals. Consenting respondents completed a two-part
      survey composed of the respondent profile sheet and the Social Skills Inventory.
      The respondent profile sheet assessed demographic profile and social media use
      profile in terms of the mode, frequency, and duration of utilization. Three
      trained team members observed each nurse-patient dyad and completed the Nurse
      Patient Bonding Instrument. RESULTS: A good fit model illustrated the negative
      effects of frequent social media use to patient openness (beta = -0.18, p < 0.05)
      and engagement (beta = -0.11, p <= 0.05). Longer use of social media on a daily
      basis, however, positively affected both dimensions of social skills. Accessing
      social media platforms using non-handheld devices showed the most influential
      positive effects to social skills and nurse-patient interaction. Additionally,
      although verbal social skills positively affected most dimensions of nurse
      patient interaction, non-verbal social skills negatively influenced patient
      engagement (beta = -0.19, p = 0.019) and nurse openness (beta = -0.38, p <=
      0.05). CONCLUSION: The structural model illustrates the effects of using social
      media on the social skills and nurse-patient interaction of nurses and emphasizes
      the need for implementing institutional policies on the judicious use and
      application of social media in the workplace. Further, social skills development
      programs geared toward having a balanced social skill must be implemented.

PMID- 29353714
TI  - MRI findings of postherpetic abdominal wall pseudohernia: A case report.
AB  - Herpes zoster is caused by the reactivation of latent varicella-zoster virus from
      dorsal root ganglia. Although infrequent, simultaneous damage to the anterior
      horn cells or anterior nerve roots at the same level may result in motor
      neuropathy. When motor involvement is localized in the abdominal wall, a
      pseudohernia may be the clinical presentation. We report a case of abdominal wall
      post-herpetic pseudohernia, with clinical, ultrasound and MRI correlation. MRI
      demonstrated increased T2/STIR signal intensity in the abdominal wall muscles,
      suggesting acute denervation. To our knowledge, this is the first case report of
      postherpetic pseudohernia with acute denervation demonstrated on MRI.

PMID- 29353715
TI  - Peering beneath the surface: juxtacortical tumors of bone (part II).
AB  - Juxtacortical or surface tumors of bone are neoplasms arising from or just
      outside the cortex, and are composed of different histologic types. Although the
      imaging appearances of these lesions have similarities to their intramedullary
      counterparts, their location alters their radiographic and MR characteristics,
      creating difficulties in diagnosis. Meanwhile, several non-neoplastic lesions,
      such as stress reaction/stress fracture and indolent infectious processes,
      compound the differential diagnosis. Neoplastic juxtacortical lesions of bone
      have been classified into five categories: cartilaginous, fibrous, lipomatous,
      osseous, and metastatic tumors. Our goal in part two of this review is to
      illustrate the characteristic radiographic, CT and MR imaging features of various
      juxtacortical neoplasms, including pathognomonic imaging findings that can aid in
      diagnosis, and to develop an appropriate differential diagnosis for surface
      lesions based on imaging characteristics, lesion location and patient age.

PMID- 29353717
TI  - Medical neglect at a tertiary paediatric hospital.
AB  - Medical neglect is under-researched and the extent of the problem in Australia is
      unknown. We conducted a review of the referrals for medical neglect to the Child
      Protection Unit (CPU) at a tertiary children's hospital in Sydney over a 5 years
      period, from 2011 to 2016, to determine what medical conditions are being
      referred, the reason for the medical neglect concern and whether cases are
      managed in line with American Academy of Pediatrics (AAP) guideline on medical
      neglect. 61 cases of medical neglect were identified, constituting 4.1% of all
      referrals to the Child Protection Unit for physical abuse and neglect. There was
      a wide variety of medical conditions. Most were chronic medical conditions (87%).
      The top two medical conditions were chronic and complex multi-system disorders
      (37.7%) and endocrine disorders (18%). The majority of medical neglect were
      related to concerns that the caregivers were unwilling to follow medical advice
      (45.9%) or unable to provide necessary medical care (26.2%). In line with the AAP
      guideline on medical neglect, all cases were managed by addressing communication
      difficulties (100%) and resource issues were addressed in 80% of cases. A report
      to statutory child protection agencies was made in 50% of cases. Directly
      observed therapy and medical contracts were used in 30% and 26% of cases. We
      conclude that children with chronic medical conditions may be at risk of medical
      neglect. Communication difficulties were a factor in all cases. Statutory agency
      intervention is often required.

PMID- 29353716
TI  - Hypovascular hypointense nodules in hepatobiliary phase without T2
      hyperintensity: long-term outcomes and added value of DWI in predicting
      hypervascular transformation.
AB  - PURPOSE: To evaluate outcomes and risk factors associated with
      hypervascularization in hypovascular, hepatobiliary phase (HBP) hypointense
      nodules (HHNs) without T2 hyperintensity on gadoxetic acid-enhanced magnetic
      resonance (MR) images in chronic liver disease patients. MATERIALS AND METHODS:
      222 HHNs were analyzed. Multivariate analysis with a Cox proportional hazard
      regression model was used. RESULTS: 41 nodules became hypervascular
      hepatocellular carcinoma (HCC). History of HCC, hyperintensity on T1WI or DWI,
      and higher growth rate were risk factors for hypervascularization (P < .05).
      CONCLUSION: History of HCC, hyperintensity on T1WI or DWI, and higher growth rate
      were associated with nodular progression to hypervascular HCC.

PMID- 29353718
TI  - Longitudinal associations between physically abusive parents' emotional
      expressiveness and children's self-regulation.
AB  - The present study took a developmental psychopathology approach to examine the
      longitudinal association between parents' emotional expressiveness and children's
      self-regulation. Data collection spanned from 2004 to 2008. Ninety-two physically
      abusive parents completed yearly assessments of their emotional expressiveness,
      as well as their children's self-regulation abilities. Observational and
      behavioral measures were also obtained yearly to capture both parents' emotional
      expressiveness and children's self-regulation. Specifically, parents participated
      in a parent-child interaction task, which provided insight into their levels of
      flat affect. A puzzle box task was completed by each child to assess self
      regulation. Results indicated, first, that greater parental expression of
      negative emotions predicted poorer self-regulation in children, both concurrently
      and across time. Second, parental expressions of positive emotions and parents'
      flat affect were unrelated to children's self-regulation. Findings inform our
      understanding of parental socialization of self-regulation and provide insight
      into the roles of distinct components of emotional expressiveness. Moreover,
      findings have crucial implications for understanding emotional expressiveness in
      high-risk samples and increase our understanding of within-group functioning
      among maltreating families that may serve as a means to direct intervention
      efforts.

PMID- 29353719
TI  - Depressive symptoms and self-harm among youngsters referred to child welfare: The
      role of trust in caregiver support and communication.
AB  - Depressive symptoms and self-harm, i.e. non-suicidal self-injury and suicidal
      behaviors, are highly prevalent in youngsters involved in Child Welfare System
      (CWS) services. Little research investigates, however, why these CWS youngsters
      are at risk. We explored whether trust in caregiver support and communication
      about experiences with primary caregivers, are associated with CWS youngsters'
      depressive symptoms and/or self-harm. An anonymous online survey of 271 CWS
      youngsters (10-21 years of age, 57.2% female) was used to assess trust and
      communication, and depressive symptoms/self-harm. Results showed significant
      negative associations between self-reported trust in maternal and paternal
      support, and depressive symptoms/self-harm. Communication about experiences with
      one's biological mother mediated the relationship between trust in maternal
      support and depressive symptoms/self-harm. Furthermore, the presence of an
      additional trustworthy caregiver buffered the impact of low trust in maternal or
      paternal support on depressive symptoms/self-harm. Implications for interventions
      targeting CWS youngsters' depressive symptoms and self-harm are discussed.

PMID- 29353720
TI  - ((S)-3-Mercapto-2-methylpropanamido)acetic acid derivatives as metallo-beta
      lactamase inhibitors: Synthesis, kinetic and crystallographic studies.
AB  - The emergence and global spread of metallo-beta-lactamase (MBL) mediated
      resistance to almost all beta-lactam antibacterials poses a serious threat to
      public health. Since no clinically useful MBL inhibitors have been reported,
      there is an urgent need to develop new potent broad-spectrum MBL inhibitors
      effective against antibacterial resistance. Herein, we synthesized a set of 2
      substituted ((S)-3-mercapto-2-methylpropanamido) acetic acid derivatives, some of
      which displayed potent inhibition with high ligand efficiency to the clinically
      relevant MBL subtypes, Verona Integron-encoded MBL (VIM)-2 and New Delhi MBL
      (NDM)-1. Kinetic studies revealed that the inhibitors are not strong zinc
      chelators in solution, and they bind reversibly to VIM-2 but dissociate very
      slowly. Crystallographic analyses revealed that they inhibit VIM-2 via chelating
      the active site zinc ions and interacting with catalytically important residues.
      Further cell- and zebrafish-based assays revealed that the inhibitors slightly
      increase susceptibility of E. coli cells expressing VIM-2 to meropenem, and they
      have no apparent toxicity to the viability of HEK293T cells and the zebrafish
      embryogenesis.

PMID- 29353721
TI  - Design, synthesis, and biological evaluation of novel catecholopyrimidine based
      PDE4 inhibitor for the treatment of atopic dermatitis.
AB  - Selective inhibition of phosphodiesterase (PDE) 4B favorably suppresses the
      synthesis of inflammatory cytokines and subsequently arrest the development of
      atopic dermatitis via modulating the intracellular cAMP levels. Considering the
      side effects of corticosteroids, selective PDE4 inhibition could constitute an
      effective alternative therapy for the treatment of atopic dermatitis (AD). In
      this study, a series of novel catechol based compounds bearing pyrimidine as the
      core have been synthesized and screened for the PDE4 inhibitory properties. The
      PDE4 selectivity of the active compounds over other PDEs has been investigated.
      Compound 23 bearing pyrimidine core functionalized with catechol, pyridine and
      trifluoromethyl groups can effectively inhibit the PDE4B with IC50 value in
      nanomolar range (IC50 = 15 +/- 0.4 nM). Compound 23 exhibited seven fold higher
      selectivity towards PDE4B over PDE4D. Molecular Docking study confirmed its
      stronger affinity towards catalytic domain of PDE4B. In-vivo analysis confirmed
      that compound 23 effectively alleviated the symptoms of atopic dermatitis in DNCB
      treated Balb/c mice by suppressing the synthesis of inflammatory mediators such
      as TNF-alpha, and Ig-E. Taken together, this study suggested that compound 23
      could be an effective PDE4 inhibitor for the potential treatment of AD.

PMID- 29353722
TI  - Hepatoprotective natural triterpenoids.
AB  - Liver diseases are one of the leading causes of death in the world. In spite of
      tremendous advances in modern drug research, effective and safe hepatoprotective
      agents are still in urgent demand. Natural products are undoubtedly valuable
      sources for drug leads. A number of natural triterpenoids were reported to
      possess pronounced hepatoprotective effects, and triterpenoids have become one of
      the most important classes of natural products for hepatoprotective agents.
      However, the significance of natural triterpenoids has been underestimated in the
      hepatoprotective drug discovery, with only very limited triterpenoids being
      covered in the reviews of hepatoprotective natural products. In this paper, ca
      350 natural triterpenoids with reported hepatoprotective effects in ca 120
      references between 1975 and 2016 will be reviewed, and the structure-activity
      relationships of certain types of natural triterpenoids, if available, will be
      discussed. Patents are not included.

PMID- 29353723
TI  - Bysspectin A, an unusual octaketide dimer and the precursor derivatives from the
      endophytic fungus Byssochlamys spectabilis IMM0002 and their biological
      activities.
AB  - Bysspectin A (1), a polyketide-derived octaketide dimer with a novel carbon
      skeleton, and two new precursor derivatives, bysspectins B and C (2 and 3), were
      obtained from an organic extract of the endophytic fungus Byssochlamys
      spectabilis that had been isolated from a leaf tissue of the traditional Chinese
      medicinal plant Edgeworthia chrysantha, together with a known octaketide,
      paecilocin A (4). Their structures were determined by HRMS, 1D and 2D NMR
      spectroscopic analysis. A plausible route for their biosynthetic pathway is
      proposed. Compounds 1-3 were tested for their antimicrobial activities. Only
      compound 3 was weakly active against Escherichia coli and Staphyloccocus aureus
      with MIC values of 32 and 64 MUg/mL, respectively. Further, the inhibitory
      effects on human carboxylesterases (hCE1, hCE2) of compounds 1 and 4 were
      evaluated. The results demonstrated that bysspectin A (1) was a novel and highly
      selective inhibitor against hCE2 with the IC50 value of 2.01 MUM. Docking
      simulation also demonstrated that active compound 1 created interaction with the
      Ser-288 (the catalytic amino-acid in the catalytic cavity) of hCE2 via hydrogen
      bonding, revealing its highly selective inhibition toward hCE2.

PMID- 29353724
TI  - Discovery of biphenyl-substituted diarylpyrimidines as non-nucleoside reverse
      transcriptase inhibitors with high potency against wild-type and mutant HIV-1.
AB  - A novel series of diarylpyrimidine (DAPY) derivatives bearing the biphenyl motif
      with multiple substituted groups was synthesized as human immunodeficiency virus
      (HIV)-1 non-nucleoside reverse transcriptase inhibitors. All of the target
      compounds were evaluated for their in vitro activity against HIV in MT-4 cells.
      Most of the compounds exhibited excellent activity with low nanomolar EC50 values
      against wild-type, single and double mutant HIV-1 strains. Compound 4b displayed
      an EC50 value of 1 nM against HIV-1 IIIB, 1.3 nM against L100I, 0.84 nM against
      K103 N, 1.5 nM against Y181C, 11 nM against Y188L, 2 nM against E138K, 10 nM
      against K103 N + Y181C, and almost 110 nM against F227L + V106. The improvement
      in the selectivity and potency of the target molecules against the wild-type and
      mutant HIV-1 strains validated our hypothesis. The biphenyl ring in the DAPY
      derivatives could strengthen the pi-pi stacking effect between the target
      molecule and the non-nucleoside inhibitor-binding pocket in the reverse
      transcriptase by extending the conjugating systems. This research represented a
      significant step toward the discovery of novel therapeutic DAPYs for treating
      acquired immunodeficiency syndrome in patients infected with HIV-1.

PMID- 29353725
TI  - Evaluation of 4-oxo-quinoline-based CB2 PET radioligands in R6/2 chorea
      huntington mouse model and human ALS spinal cord tissue.
AB  - The cannabinoid receptor 2 (CB2) has been implicated in a series of
      neurodegenerative disorders and has emerged as an interesting biological target
      for therapeutic as well as diagnostic purposes. In the present work, we describe
      an improved radiosynthetic approach to obtain the previously reported CB2
      specific PET radioligand [18F]RS-126 in higher radiochemical yields and molar
      activities. Additionally, the study revealed that prolongation of the [18F]RS-126
      fluoroalkyl side chain ultimately leads to an improved stability towards mouse
      liver enzymes but is accompanied by a reduction in selectivity over the
      cannabinoid receptor 1 (CB1). Huntington-related phenotypic changes as well as
      striatal D2R downregulation were confirmed for the transgenic R6/2 mouse model.
      CB2 upregulation in R6/2 Chorea Huntington mice was observed in hippocampus,
      cortex, striatum and cerebellum by qPCR, however, these results could not be
      confirmed at the protein level by PET imaging. Furthermore, we evaluated the
      utility of the newly developed [11C]RS-028, a potent [18F]RS-126 derivative with
      increased polarity and high selectivity over CB1 in post-mortem human ALS spinal
      cord and control tissue. Applying in vitro autoradiography, the translational
      relevance of CB2 imaging was demonstrated by the specific binding of [11C]RS-028
      to post-mortem human ALS spinal cord tissue.

PMID- 29353727
TI  - Synthesis of novel 5-amino-1,3,4-thiadiazole-2-sulfonamide containing acridine
      sulfonamide/carboxamide compounds and investigation of their inhibition effects
      on human carbonic anhydrase I, II, IV and VII.
AB  - Herein, we report that acridine intermediates 5 were obtained from the reduction
      of nitro acridine derivatives 4, which were synthesized via condensation of
      dimedone, p-nitrobenzaldehyde with 4-amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2
      yl)benzamide, respectively. Then acridine sulfonamide/carboxamide (7a-i)
      compounds were synthesized by reaction of amino acridine 5 with sulfonyl
      chlorides and carbamoyl chlorides. The new compounds were characterized by
      melting points, FT-IR, 1H NMR, 13C NMR and HRMS analyzes. The evaluation of in
      vitro test of the synthesized compounds against hCA I, II, IV and VII showed that
      some of them are potent inhibitors. Among them, compound 7e showed the most
      potent activity against hCA II with a KI of 7.9 nM.

PMID- 29353726
TI  - Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive,
      multipotent agents for Alzheimer's disease treatment.
AB  - A novel series of 9-amino-1,2,3,4-tetrahydroacridine and 5,6-dichloronicotinic
      acid moiety were conjugated with different linkers. Afterwards new derivatives
      were evaluated as potential multifunctional acetylcholinesterase inhibitors
      (AChEIs), anti-Alzheimer's disease (AD) drug candidates. All the compounds were
      synthesized and tested for capacity for the inhibition of acetylcholinesterase
      (AChE) and butyrylcholinesterase (BuChE) enzymes. Specifically, the most
      promising derivative 3b (IC50 = 1.02 nM) had higher inhibitory potency compared
      to the reference drug, tacrine. Consequently, kinetic studies of 3b compound
      showed a mixed-type inhibition of both AChE and BuChE. Afterwards the best potent
      AChE inhibitor has been examined on amyloid beta (Abeta) self-induced
      aggregation. Furthermore, 3b compound was tested in various concentrations and
      had moderate activity against Abeta aggregation. Inhibition of Abeta aggregation
      was 46.63% and 19.41% at 50 MUM and 5  MUM concentrations, respectively.
      Moreover, no cytotoxicity was observed for the mentioned concentrations.
      Therefore, 3b compound is a promising multipotent agent for the treatment of AD.

PMID- 29353728
TI  - Synthesis of pyrazole acrylic acid based oxadiazole and amide derivatives as
      antimalarial and anticancer agents.
AB  - Depravity of malaria in terms of morbidity and mortality in human beings makes it
      a major health issue in tropical and subtropical areas of the globe. Drug
      counterfeiting and non-adherence to the treatment regimen have significantly
      contributed to development and spread of multidrug resistance that has
      highlighted the need for development of novel and more efficient antimalarial
      drugs. Complexity associated with cancer disease and prevalence of diversified
      cell populations vindicates highly specific treatment options for treatment of
      cancer. Resistance to these anticancer agents has posed a great hindrance in
      successful treatment of cancer. Pondering this ongoing situation, it was
      speculated to develop novel compounds targeting malaria and cancer. Moving on the
      same aisle, we synthesized pyrazole acrylic acid based oxadiazole and amide
      derivatives using multi-step reaction pathways (6a-x; 6a'-h'). Schizont
      maturation inhibition assay was employed to determine antimalarial potential.
      Compound 6v emerged as the most potent antimalarial agent targeting falcipain-2
      enzyme. Anticancer activity was done using sulforhodamine B assay. Compounds 6b'
      and 6g' demonstrated promising results against all the tested cell lines.
      Further, Microscopic view clearly indicated formation of apoptotic bodies,
      chromatin condensation, shrinkage of cells and bleb formation. Validation of the
      results was achieved using molecular docking studies. From the obtained results,
      it was observed that cyclization (oxadiazole) favored antimalarial activity while
      non-cyclized compounds (amides) emerged as better anticancer agents.

PMID- 29353729
TI  - Design, synthesis and biological evaluation of bitopic arylpiperazine-hexahydro
      pyrazinoquinolines as preferential dopamine D3 receptor ligands.
AB  - Three series of bitobic arylpiperazine-phenyl-hexahydropyrazinoquino- lines
      analogues were designed, synthesizedand evaluated as a novel class of selective
      ligands for the dopamine D3 receptor. Compounds 15a (Ki of 11.7 +/- 1.8 and 373
      nM at D3 and D2, respectively), 15c (Ki of 5.49 and 264 nM at D3 and D2,
      respectively), 15e (Ki of 14.9 and 325 nM at D3 and D2, respectively), 15i (Ki of
      13.8 and 401 nM at D3 and D2, respectively) and 15l (Ki of 13.6 and 870 nM at D3
      and D2, respectively) were found to demonstrate good binding affinity and
      selectivity, and especially compound 15c showeda similar binding affinity and
      selectivity compared with the contrast drug BP897.

PMID- 29353730
TI  - Benzopyrone represents a privilege scaffold to identify novel adenosine A1/A2A
      receptor antagonists.
AB  - Adenosine receptor antagonists are under investigation as potential drug
      candidates for the treatment of certain cancers, neurological disorders,
      depression and potentially improve tumour immunotherapy. The benzo-gamma-pyrone
      scaffold is well-known in medicinal chemistry with diverse pharmacological
      activities attributed to them, however, their therapeutic potential as adenosine
      receptor antagonists have not been investigated in detail. To expand on the
      structure-activity relationships, the present study explored the adenosine A1 and
      A2A receptor binding affinities of a selected series of benzo-gamma-pyrone
      analogues. In vitro evaluation led to the identification of 5-hydroxy-2-(3
      hydroxyphenyl)-4H-1-benzopyran-4-one with the best adenosine A2A receptor
      affinity among the test compounds and was found to be non-selective (A1Ki = 0.956
      uM; A2AKi = 1.44 uM). Hydroxy substitution on ring A and/or B play a key role in
      modulating the binding affinity at adenosine A1 and A2A receptors. Adenosine A1
      receptor affinity was increased to the nanomolar range with hydroxy substitution
      on C6 (ring A), while meta-hydroxy substitution on ring B governed adenosine A2A
      receptor affinity. The double bond between C2 and C3 of ring C as well as C2
      phenyl substitution was shown to be imperative for both adenosine A1 and A2A
      receptor affinity. Selected benzo-gamma-pyrone derivatives behaved as adenosine
      A1 receptor antagonists in the performed GTP shift assays. It may be concluded
      that benzo-gamma-pyrone based derivatives are suitable leads for designing and
      identifying adenosine receptor antagonists as treatment of various disorders.

PMID- 29353731
TI  - Evaluating hydrophobic galactonoamidines as transition state analogs for
      enzymatic beta-galactoside hydrolysis.
AB  - A spectroscopic examination of six galactonoamidines with inhibition constants
      and efficacy in the low nanomolar concentration range (Ki = 6-11 nM, IC50 = 12-36
      nM) suggested only two of them as putative transition state analogs for the
      hydrolysis of beta-galactosides by beta-galactosidase (A. oryzae). A rationale
      for the experimental results was elaborated using docking and molecular dynamics
      studies. An analysis of the combined observations reveals several common factors
      of the compounds suggested as transition state analogs (TSAs): the putative TSAs
      have a similar orientation in the active site; show conserved positioning of the
      glycon; display a large number of H-bond interactions toward the catalytically
      active amino acid residues via their glycon; and exhibit hydrophobic interactions
      at the outer rim of the active site with small changes of the position and
      orientation of their respective aglycons.

PMID- 29353732
TI  - Cunninghamella blakesleeana-mediated biotransformation of a contraceptive drug,
      desogestrel, and anti-MDR-Staphylococcus aureus activity of its metabolites.
AB  - Staphylococcus aureus is one of the most infectious agents among staphylococcal
      bacteria. Currently many strains of S. aureus have developed resistance against
      available antibiotics. Therefore, the treatment of infections caused by them is a
      major challenge. During current study, desogestrel (1), a contraceptive drug, was
      found to be a potent growth inhibitor of drug resistant strains of S. aureus.
      Therefore, in search of new and effective agents against multi-drug resistant S.
      aureus strains, whole-cell bio-catalytic conversion of desogestrel (1) by
      Cunninghamella blakesleeana ATCC 8688A at pH 7.0 and 25  degrees C was carried
      out, yielding three new metabolites, 13-ethyl-11-methylene-18,19-dinor-17alpha
      pregn-4-en-20-yn-6beta,15beta,17beta-triol (2), 13-ethyl-11-methylene-18,19-dinor
      17alpha-pregn-4-en-20-yn-3beta,6beta,17beta-triol (3), and 13-ethyl-11-methylene
      18,19-dinor-17alpha-pregn-20-yn-3alpha,5alpha,6beta,17beta-tetraol (4), along
      with a known metabolite, 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20
      yn-6beta,17beta-dihydroxy-3-one (5). Among them, compounds 1-2 showed a potent
      activity against S. aureus EMRSA-17, S. aureus NCTC 13277 (MRSA-252), and S.
      aureus NCTC 13143, and clinically isolated Pakistani strain of S. aureus in an in
      vitro Microplate Alamar Blue Assay (MABA). Vancomycin was used as the standard
      drug in this assay. In addition, compound 1 also showed a significant activity
      against vancomycin-resistant S. aureus (VRSA) ATCC 700699. Compounds 1-5 were
      also evaluated against 3T3 normal cell line (mouse fibroblast) where they all
      were identified as non-cytotoxic. The present study thus provides new leads for
      the development of anti-bacterial drugs against MDR S. aureus.

PMID- 29353733
TI  - In-vitro evaluation of antioxidant, anti-elastase, anti-collagenase, anti
      hyaluronidase activities of safranal and determination of its sun protection
      factor in skin photoaging.
AB  - Safranal, a monoterpene aldehyde, is present as one of the main volatile
      constituents of Crocus sativus Linn. (saffron flowers). This volatile constituent
      not only contributes to the aroma of saffron but has been reported to possess
      antidiabetic, antiulcer, antiasthamatic, anticonvulsant, antidepressant,
      cardioprotective, anticancer and UV protective properties. Most of these
      therapeutic actions are contributed by its potential to quench reactive oxygen
      species (ROS). Antioxidant properties of phytoconstituents are now being explored
      for developing photoprotective skin formulations. These bioactives have the
      potential to protect the epidermal and dermal layers of the skin which mainly
      comprises of elastin and collagen. When UV rays penetrate the dermal layers,
      there is an increased production of elastase, collagenase and hyaluronidase
      leading to degradation of collagen, elastin and hyaluronic acid respectively.
      These dermal components are responsible to provide strength, elasticity and
      moisture to the skin. Due to frequent exposure to sunlight, these conditions tend
      to augment leading to wrinkle formation and sagging of skin. Although antioxidant
      properties of safranal have been established on various cell lines but till date
      no studies have been reported regarding the dermal enzyme inhibition activities.
      In the current research work, a comprehensive in vitro evaluation of antioxidant,
      anti-elastase, anti-collagenase, anti-hyaluronidase activities of safranal along
      with determination of sun protection factor (SPF) was carried out. The in vitro
      antioxidant activity was carried out by diphenylpicrylhydrazyl (DPPH) method and
      its IC50 value was found to be 22.7 MUg/ml. The enzyme inhibition IC50 values of
      safranal for anti elastase activity were found to be 43.6 MUg/ml, 70 MUg/ml for
      antihyaluronidase activity and 9.4 MUg/ml for anticollagenase activity.
      Photoprotective activity of safranal was determined by UV absorbance method and
      SPF calculated by Mansur equation which was found to be 6.6. The significant
      inhibitory activity of safranal on matrix metalloproteinases (MMPs) responsible
      for aging and a higher SPF established that this bioorganic molecule is a strong
      photoprotective agent. Its established free radical scavenging capability along
      with above characteristics make it a valuable component to be incorporated into
      herbal antiaging formulations.

PMID- 29353734
TI  - Parental ethnicity associated with risk for multiple sclerosis: A population
      based incident case-control study in Iran.
AB  - BACKGROUND: The epidemiology of multiple sclerosis (MS) includes a consideration
      of geography and population ethnicity. To determine whether there is any
      association between ethnicity and risk of MS in a multiethnic, population-based
      case-control study. METHODS: We conducted a population-based case-control of 547
      incident MS cases and 1057 healthy controls between August 2013 and February
      2015, Tehran, a multi-ethnic city. The patients were identified and enrolled
      through the Iranian MS Society. Case status was confirmed by a panel of MS
      specialists beside of 2010 McDonald criteria. Controls were selected through
      random digit dialing. A logistic regression model was applied to estimate the
      odds ratios (95%CI) adjusted for age, sex, tobacco smoking and socioeconomic
      status. RESULTS: The risk of MS for Kurd, Turk and Fars ethnicities was
      apparently smaller compared to one specific ethnic background (Lor); OR 0.36
      (0.15-0.86) for Kurd, OR 0.42 (0.24-0.74) for Turk and OR 0.53 (0.31-0.89) for
      Fars. Heterogeneity in parental ethnicity of common ethnic groups was
      significantly associated with increased risk of MS OR 1.61 (1.13-2.29). All
      associations remained after adjustment for relevant confounders. CONCLUSIONS: MS
      was unequally distributed in the ethnic groups. Moreover, heterogeneity in
      parental ethnicity seems to be a risk factor for MS.

PMID- 29353735
TI  - Treatment for paraneoplastic neuromyelitis optica spectrum disorder (NMOsd):
      Probable effects of tocilizumab for both cancer and NMOsd.

PMID- 29353736
TI  - Mitochondrial leukoencephalopathies: A border zone between acquired and inherited
      white matter disorders in children?
AB  - BACKGROUND: There is emerging evidence implicating mitochondrial dysfunction in
      the pathogenesis of acquired demyelinating disorders such as multiple sclerosis.
      On the other hand, some of the primary mitochondrial disorders such as
      mitochondrial leukoencephalopathies exhibit evidence of neuroinflammation on MRI.
      The inter-relationship between mitochondrial disorders and episodic CNS
      inflammation needs exploration because of the therapeutic implications.
      OBJECTIVE: We sought to analyze the clinical course and MRI characteristics in a
      cohort of patients with mitochondrial leukoencephalopathy to determine features,
      if any, that mimic primary demyelinating disorders. Therapeutic implications of
      these findings are discussed. PATIENTS AND METHODS: Detailed analysis of the
      clinical course, magnetic resonance imaging findings and therapeutic response was
      performed in 14 patients with mitochondrial leukoencephalopathy. The diagnosis
      was ascertained by clinical features, histopathology, respiratory chain enzyme
      assays and exome sequencing. RESULTS: Fourteen patients [Age at evaluation: 2-7
      yrs, M: F-1:1] were included in the study. The genetic findings included
      variations in NDUFA1 (1); NDUFV1 (4); NDUFS2 (2); LYRM (2);MPV17(1); BOLA3(2);
      IBA57(2). Clinical Features which mimicked acquired demyelinating disorder
      included acute onset focal deficits associated with encephalopathy [10/14, 71%],
      febrile illness preceding the onset [7/14, 50%] unequivocal partial or complete
      steroid responsiveness [11/11], episodic/ relapsing remitting neurological
      dysfunction [10/14, 71%] and a subsequent stable rather than a progressive course
      [12/14, 85%]. MRI characteristics included confluent white matter lesions [14/14,
      100%], diffusion restriction [11/14,78.5%], contrast enhancement [13/13,100%],
      spinal cord involvement [8/13,61.5%], lactate peak on MRS [13/13] and white
      matter cysts [13/14, 92.8%]. CONCLUSION: Clinical presentations of mitochondrial
      leukoencephalopathy often mimic an acquired demyelinating disorder. The
      therapeutic implications of these observations require further exploration.

PMID- 29353737
TI  - Biomarkers identification for PML monitoring, during Natalizumab (Tysabri(r))
      treatment in Relapsing-Remitting Multiple Sclerosis.
AB  - Natalizumab (NTZ, Tysabri(r); Biogen-Idec, Cambridge, MA, USA) is a humanized
      anti-alpha4 integrin monoclonal antibody, largely used in the treatment of
      Relapsing-Remitting Multiple Sclerosis (RRMS). Although the drug has shown great
      efficacy in clinical trials (AFFIRM and SENTINEL) and in post-marketing
      observational studies (TYGRIS), by reducing clinical signs as disability status
      progression, brain lesions and annual relapse rate, there are numerous papers
      concerning the associated risk of progressive multifocal leukoencephalopathy
      (PML). PML is a brain infection caused by John Cunningham virus (JCV) and its
      incidence is related to intrinsic and extrinsic risk factors, such as long-term
      natalizumab therapy (more than 24 infusion doses), previous pharmacological
      immunosuppressive treatment and JVC antibody-positive status. The identification
      of risk factors provides an instrument to improve treatment decisions and to
      obtain an accurate benefit-risk evaluation. In order to evaluate the most
      appropriate natalizumab-MS therapy and to obtain minor incidence of PML, an
      accurate description of risk factors and a biological markers identification are
      needed. This article review aims to list some biomarkers that have been proposed
      to evaluate the safety of natalizumab therapy.

PMID- 29353738
TI  - Neuroticism, schizotypy, and scale anchors influence eye movement behaviour in
      the visual exploration of abstract art: An exploratory study.
AB  - The same piece of artwork can attract both admiration and rejection from
      different people. One potential explanation for this effect is individual
      differences in perceptual biases, which influence the way in which we see
      different aspects of the same image. We explored the relationship between
      individual differences (i.e., personality) and eye movements for examinations of
      abstract art. Images were presented for 5000ms, after which participants judged
      aesthetic appeal and perceived value using visual analogue scales. Scale anchor
      labels (Looks Good/Looks Bad; $0/$5000) were counterbalanced between participants
      such that positive labels were on the left half of the time and on the right half
      of the time. Overall, more fixations occurred to the right and upper visual
      fields. Neuroticism significantly predicted the proportion of fixations to the
      left, whereas cognitive disorganisation negatively predicted the proportion of
      fixations to upper space. Participants found images more aesthetically pleasing
      and more valuable when positive anchors were on the left. Findings demonstrate
      that personality traits influence fixation patterns. Further, the positioning of
      positive anchor labels on the left leads to higher ratings of visual stimuli.

PMID- 29353739
TI  - Generation of matched patient-derived xenograft in vitro-in vivo models using 3D
      macroporous hydrogels for the study of liver cancer.
AB  - Hepatocellular carcinoma (HCC) is the third leading cause of cancer death
      worldwide, often manifesting at the advanced stage when cure is no longer
      possible. The discrepancy between preclinical findings and clinical outcome in
      HCC is well-recognized. So far, sorafenib is the only targeted therapy approved
      as first-line therapy for patients with advanced HCC. There is an urgent need for
      improved preclinical models for the development of HCC-targeted therapies.
      Patient-derived xenograft (PDX) tumor models have been shown to closely
      recapitulate human tumor biology and predict patient drug response. However, the
      use of PDX models is currently limited by high costs and low throughput. In this
      study, we engineered in vitro conditions conducive for the culture of HCC-PDX
      organoids derived from a panel of 14 different HCC-PDX lines through the use of a
      three-dimensional macroporous cellulosic sponge system. To validate the in vitro
      HCC-PDX models, both in vivo and in vitro HCC-PDX models were subjected to whole
      exome sequencing and RNA-sequencing. Correlative studies indicate strong
      concordance in genomic and transcriptomic profiles as well as intra-tumoral
      heterogeneity between each matched in vitro-in vivo HCC-PDX pairs. Furthermore,
      we demonstrate the feasibility of using these in vitro HCC-PDX models for drug
      testing, paving the way for more efficient preclinical studies in HCC drug
      development.

PMID- 29353741
TI  - Simulating the effect of muscle weakness and contracture on neuromuscular control
      of normal gait in children.
AB  - Altered neural control of movement and musculoskeletal deficiencies are common in
      children with spastic cerebral palsy (SCP), with muscle weakness and contracture
      commonly experienced. Both neural and musculoskeletal deficiencies are likely to
      contribute to abnormal gait, such as equinus gait (toe-walking), in children with
      SCP. However, it is not known whether the musculoskeletal deficiencies prevent
      normal gait or if neural control could be altered to achieve normal gait. This
      study examined the effect of simulated muscle weakness and contracture of the
      major plantarflexor/dorsiflexor muscles on the neuromuscular requirements for
      achieving normal walking gait in children. Initial muscle-driven simulations of
      walking with normal musculoskeletal properties by typically developing children
      were undertaken. Additional simulations with altered musculoskeletal properties
      were then undertaken; with muscle weakness and contracture simulated by reducing
      the maximum isometric force and tendon slack length, respectively, of selected
      muscles. Muscle activations and forces required across all simulations were then
      compared via waveform analysis. Maintenance of normal gait appeared robust to
      muscle weakness in isolation, with increased activation of weakened muscles the
      major compensatory strategy. With muscle contracture, reduced activation of the
      plantarflexors was required across the mid-portion of stance suggesting a greater
      contribution from passive forces. Increased activation and force during swing was
      also required from the tibialis anterior to counteract the increased passive
      forces from the simulated dorsiflexor muscle contracture. Improvements in
      plantarflexor and dorsiflexor motor function and muscle strength, concomitant
      with reductions in plantarflexor muscle stiffness may target the deficits
      associated with SCP that limit normal gait.

PMID- 29353740
TI  - Gait in patients with adolescent idiopathic scoliosis. Effect of surgery at 10
      years of follow-up.
AB  - PURPOSE: To assess radiological and gait biomechanical changes before, at one and
      10 years after surgery in AIS patients. METHODS: This clinical prospective study
      included fifteen adult women (mean[SD] age: 26 [1] years) diagnosed with thoraco
      lumbar/lumbar AIS and operated 10 years ago. Clinical, radiological and gait
      variables, including kinematics, electromyography (EMG), mechanics and energetics
      were compared between presurgery (S0), 1 year (S1) and 10 years (S2) postsurgery
      period using a one way repeated measure ANOVA. RESULTS: The Cobb angle of the
      scoliosis curve was reduced by 55% at 1 year postsugery but only by 37% at 10
      years postsurgery suggesting a loss of 32% over time. Frontal plumb line C7-S1
      distance was significantly improved by surgery (-44%) and remained stable at 10
      years postsurgery. Lower limb kinematics was not affected by the surgery at long
      term. Excessive bilateral activation of lombo-pelvic muscles, observed before
      surgery, decreased significantly at S1 and S2 period. Mechanical energy increased
      significantly between S0, S1 and S2 session, without any change for the energetic
      variables. CONCLUSIONS: Between 1 and 10 years post-surgery, thoraco
      lumbar/lumbar AIS women showed a few decompensation of the curve without any
      change of the improved frontal body balance. Lower limbs and pelvic motion,
      during gait, was not affected by the surgery. But presurgical excessive EMG
      activity of the lumbo-pelvic muscle and reduced mechanical energy produced to
      walk get similar to normal patterns. Only the oxygen consumption remained
      excessive probably due to physical deconditioning or postural instability.

PMID- 29353742
TI  - Trunk, pelvis and hip biomechanics in individuals with femoroacetabular
      impingement syndrome: Strategies for step ascent.
AB  - BACKGROUND: Femoroacetabular impingment (FAI) syndrome is common among young
      active adults and a proposed risk factor for the future development of hip
      osteoarthritis. Pain is dominant and drives clinical decision-making. Evidence
      for altered hip joint function in this patient population is inconsistent, making
      the identification of treatment targets challenging. A broader assessment,
      considering adjacent body segments (i.e. pelvis, trunk) and individual movement
      strategies, may better inform treatment programs. This exploratory study aimed to
      compare trunk, pelvis, and hip biomechanics during step ascent between
      individuals with and without FAI syndrome. METHODS: Fifteen participants
      diagnosed with symptomatic cam-type or combined (cam plus pincer) FAI who were
      scheduled for arthroscopic surgery, and 11 age-, and sex-comparable pain- and
      disease-free individuals, underwent three-dimensional motion analysis during a
      step ascent task. Trunk, pelvis and hip biomechanics were compared between
      groups. RESULTS: Participants with FAI syndrome exhibited altered ipsilateral
      trunk lean and pelvic rise towards the symptomatic side during single-leg support
      compared to controls. Alterations were not uniformly adopted across all
      individuals with FAI syndrome; those who exhibited more pronounced alterations to
      frontal plane pelvis control tended to report pain during the task. There were
      minimal between-group differences for hip biomechanics. CONCLUSION: Exploratory
      data suggest biomechanics at the trunk and pelvis during step ascent differ
      between individuals with and without FAI syndrome. Those with FAI syndrome
      implement a range of proximal strategies for task completion, some of which may
      have relevance for rehabilitation. Longitudinal investigations of larger cohorts
      are required to evaluate hypothesized clinical and structural consequences.

PMID- 29353743
TI  - Long-term development of overcorrection after femoral derotation osteotomy in
      children with cerebral palsy.
AB  - BACKGROUND: Recent studies showed rates of recurrence of internal rotation gait
      (IRG) after femoral derotation osteotomy (FDO) up to 40%. Some surgeons even
      advice overcorrection during FDO to avoid a later recurrence. RESEARCH QUESTION:
      Evaluation of the long-term development of limbs with initial overcorrection
      after FDO. METHODS: 29 limbs of 20 children (9.9 +/- 3.2 years at surgery) with
      IRG, cerebral palsy (CP) and more than 5 degrees  external hip rotation
      postoperatively were included retrospectively. A gait analysis and clinical
      examination were performed preoperatively (less than one year, E0),
      postoperatively (9-23 months, E1) and at the long-term follow-up (at least five
      years postoperatively, E2). Differences between those children that remained
      overcorrected at E2 and those with a hip rotation within normal range at E2 were
      evaluated. RESULTS: At E2 41% of these limbs remained overcorrected, 52% showed a
      hip rotation within normal range and 7% showed recurrence of IRG. A comparison of
      those limbs that remained overcorrected and those ending within normal range
      revealed neither a difference in age at surgery nor in static and dynamic
      torsional parameters at E0 and E1 except for pelvic rotation. A significantly
      larger pelvic internal rotation at E1 for those with remaining overcorrection
      could be identified. SIGNIFICANCE: A general overcorrection during FDO in
      children with CP to avoid recurrence of IRG cannot be recommended, as 41% remain
      overcorrected. Preoperative predictors for long-term development couldn't be
      identified. If pelvic mal-rotation is corrected, hip rotation may change into
      normal range over the time in combination with the development of a flexed knee
      gait.

PMID- 29353744
TI  - Methods to assess patellofemoral joint stress: A systematic review.
AB  - Changes in patellofemoral joint (PFJ) stress are related to the development and
      course of PFJ dysfunctions. Different methods for PFJ stress calculation have
      been used, making the comparison of PFJ stress values across different studies
      difficult. The purpose of this study was to systematically review the methods for
      PFJ stress calculation and highlight the differences among the methods. A
      systematic literature search was conducted in Medline, Embase, CINAHL,
      SPORTDiscus and Web of Science databases. Included studies examined PFJ stress in
      subjects with or without musculoskeletal conditions. Of 12,670 identified
      studies, 53 were included, with a total of 1134 subjects evaluated. The main
      differences among the methods to calculate PFJ stress were: i) method to
      calculate PFJ contact area; ii) method to calculate a constant (coefficient k)
      that defines the relation between quadriceps force and PFJ reaction force; iii)
      the inclusion of adjustments for sagittal plane forces. Considerable variability
      in PFJ stress results was observed. The greatest PFJ stress value was 55.03 MPa
      during a dance jump and the lowest value was 1.9 MPa during walking at the speed
      of 1.4 m/s. Most studies applied methods which use data from previous studies.
      However, methods which use data from their own participants for most parts of the
      calculation might be preferred to minimize potential errors. When direct measures
      are not possible, a standard method could be applied to facilitate comparisons
      among studies.

PMID- 29353745
TI  - Comparison of soft tissue artifact and its effects on knee kinematics between non
      obese and obese subjects performing a squatting activity recorded using an
      exoskeleton.
AB  - BACKGROUND: Rigid attachment systems are one of the methods used to compensate
      for soft tissue artifact (STA) inherent in joint motion analyses. RESEARCH
      QUESTION: The goal of this study was to quantify STA of an exoskeleton design to
      reduce STA at the knee, and to assess the accuracy of 3D knee kinematics recorded
      with the exoskeleton in non-obese and obese subjects during quasi-static weight
      bearing squatting activity using biplane radiography. METHODS: Nine non-obese and
      eight obese subjects were recruited. The exoskeleton was calibrated on each
      subject before they performed a quasistatic squatting activity in the EOS(r)
      imaging system. 3D models of exoskeleton markers and knee bones were
      reconstructed from EOS(r) radiographs; they served to quantify STA and to
      evaluate differences between the markers and bones knee kinematics during the
      squatting activity. RESULTS: The results showed that STA observed at the femur
      was larger in non-obese subjects than in obese subjects in frontal rotation (p =
      0.004), axial rotation (p = 0.000), medio-lateral displacement (p = 0.000) and
      antero-posterior displacement (p = 0.019), while STA observed at the tibia was
      lower in non-obese subjects than in obese subjects for the three rotations (p <
      0.05) and medio-lateral displacement (p = 0.015). Differences between the markers
      and bones knee kinematics increased with knee flexion and were similar in both
      groups, except for abduction-adduction: 4.9 degrees  for non-obese subjects
      against 2.3 degrees  for obese subjects (p = 0.011). SIGNIFICANCE: This study
      demonstrated that STA at the femur and its impact on knee abduction-adduction
      using a specific exoskeleton were greater among non-obese subjects than obese
      subjects, which is encouraging for future biomechanical studies on pathologies
      such as osteoarthritis.

PMID- 29353747
TI  - Modelling for reactor-style aerobic composting based on coupling theory of mass
      heat-momentum transport and Contois equation.
AB  - This study establishes an optimal mathematical modelling to rationally describe
      the dynamic changes and spatial distribution of temperature and oxygen
      concentration in the aerobic composting process using coupling mass-heat-momentum
      transfer based on the microbial mechanism. Two different conditional composting
      experiments, namely continuous aeration and intermittent aeration, were performed
      to verify the proposed model. The results show that the model accurately
      predicted the dynamic changes in temperature (case I: R2 = 0.93, RMSE = 1.95 K;
      case II: R2 = 0.86, RMSE = 4.69 K) and oxygen concentration (case I: R2 = 0.90,
      RMSE = 1.26%; case II: R2 = 0.75, RMSE = 2.93%) in the central point of compost
      substrates. It also systematically simulated fluctuations in oxygen concentration
      caused by boundary conditions and the spatial distribution of the actual
      temperature and oxygen concentration. The proposed model exhibits good
      applicability in simulating the actual working conditions of aerobic composting
      process.

PMID- 29353746
TI  - Computational fluid dynamics modeling of carbon dioxide capture from air using
      biocatalyst in an airlift reactor.
AB  - In this work, a novel three-phase and three dimensional CFD model based on the
      Euler-Euler approach developed for modeling the hydrodynamic, mass transfer and
      CO2 fixation using microalgae in an internal loop airlift reactor with internal
      sparger. The main objective of this work was to development of CFD codes in order
      to simulate the CO2 biofixation process under different input gas velocity during
      11 days of culture time and simulate the unsteady state mass transfer based on
      Surface-Renewal-Stretch (SRS) model. The CFD results were compared with the our
      previous experimental work and they showed good agreement with a margin of less
      than 10%. This paper illustrated the ability of the CFD in complex process
      simulation such as CO2 biofixation in the airlift reactor and provided a useful
      basis for further study.

PMID- 29353748
TI  - Heteropoly acid catalytic treatment for reactivity enhancement and viscosity
      control of dissolving pulp.
AB  - The reactivity enhancement and viscosity control are of practical importance
      during the manufacture of high-quality cellulose (also known as dissolving pulp).
      In the study, the concept of using phosphotungstic acid (HPW) for this purpose
      was demonstrated. The Fock reactivity of resultant pulp increased from 49.1% to
      74.1% after the HPW catalytic treatment at a dosage of 86.4 mg HPW/g odp. The
      improved results can be attributed to the increased fiber accessibility, thanks
      to the favorable fiber morphologic changes, such as increased pore volume/size,
      water retention value and specific surface area. HPW can be readily
      recycled/reused by evaporating method, where maintaining 87.1% catalytic activity
      after six recycle times. The HPW catalytic treatment concept may provide a green
      alternative for the manufacture of high-quality dissolving pulp.

PMID- 29353749
TI  - Using Chlorella vulgaris to treat toxic excess sludge extract, and identification
      of its response mechanism by proteomics approach.
AB  - Chlorella vulgaris was cultivated in varying proportions of toxic sludge extracts
      obtained from a sequencing batch reactor for treating synthetic wastewater
      containing chlorophenols. C. vulgaris could reduce the ecotoxicity from sludge
      extracts, and a positive correlation was noted between ecotoxicity removal and
      total organic carbon removal. In terms of cell density, the optimal proportion of
      sludge extracts required for the cultivation of C. vulgaris was lower than 50%.
      The correlation between protein content in per 106 algae and inhibition extent of
      ecotoxicity of the 5 groups on the day of inoculation (0.9182, p < .05) indicated
      a positive relationship between algal protein secretion and ecotoxicity.
      According to the protein expression and differential protein expression analysis,
      we concluded that C. vulgaris produced proteins that involved in the stress
      response/redox system and energy metabolism/biosynthesis to respond to the toxic
      environment and some other proteins related to mixotrophic metabolism.

PMID- 29353750
TI  - Corn silage fungal-based solid-state pretreatment for enhanced biogas production
      in anaerobic co-digestion with cow manure.
AB  - The objective of this research was to use white-rot fungus Trametes versicolor
      for corn silage pretreatment and to investigate the effect of pretreatment on
      biogas productivity. Semi-continuous pilot-scale experiment, comprised of two
      experimental phases, was carried out. In the first phase, operational conditions
      of the full-scale biogas plant were reproduced at pilot-scale. In that phase, the
      reactor was daily fed with the mixture of cow manure, digestate from industrial
      postfermentor, corn grits and ensiled corn silage, and the average methane
      generation rate was 0.167 m3CH4 kgVS-1. In the second phase, corn grits and
      ensiled corn silage were replaced with corn silage pretreated with T. versicolor,
      and the average methane generation rate increased up to 0.236 m3CH4 kgVS-1. The
      results of this study suggest that application of fungal-based solid-state
      pretreated corn silage has positive effect on pH stability and increase the
      biogas productivity.

PMID- 29353751
TI  - Metagenomic analysis of antibiotic resistance genes in coastal industrial
      mariculture systems.
AB  - The overuse of antibiotics has posed a propagation of antibiotic resistance genes
      (ARGs) in aquaculture systems. This study firstly explored the ARGs profiles of
      the typical mariculture farms including conventional and recirculating systems
      using metagenomics approach. Fifty ARGs subtypes belonging to 21 ARGs types were
      identified, showing the wide-spectrum profiles of ARGs in the coastal industrial
      mariculture systems. ARGs with multiple antibiotics resistance have emerged in
      the mariculure systems. The co-occurrence pattern between ARGs and microbial taxa
      showed that Proteobacteria and Bacteroidetes were potential dominant hosts of
      ARGs in the industrial mariculture systems. Typical nitrifying bacteria such as
      Nitrospinae in mariculture systems also carried with some resistance genes.
      Relative abundance of ARGs in fish ponds and wastewater treatment units was
      relatively high. The investigation showed that industrial mariculture systems
      were important ARGs reservoirs in coastal area, indicating the critical role of
      recirculating systems in the terms of ARGs pollution control.

PMID- 29353752
TI  - Steam explosion enhances digestibility and fermentation of corn stover by
      facilitating ruminal microbial colonization.
AB  - The purpose of this study was to evaluate steam explosion as a pretreatment to
      enhance degradation of corn stover by ruminal microbiome. The steam explosion
      conditions were first optimized, and then the efficacy of steam explosion was
      evaluated both in vitro and in vivo. Steam explosion altered the physical and
      chemical structure of corn stover as revealed by scanning electron microscopy
      (SEM) and Fourier-transform infrared (FTIR) spectroscopy, respectively, and
      increased its cellulose content while decreasing hemicellulose content. Steam
      exploded corn stover also increased release of reducing sugars, rate of
      fermentation, and production of volatile fatty acids (VFAs) in vitro. The steam
      explosion treatment increased microbial colonization and in situ degradation of
      cellulose and hemicellulose of corn stover in the rumen of dairy cows. Steam
      explosion may be a useful pretreatment of corn stover to improve its nutritional
      value as forage for cattle, or as feedstock for biofuel production.

PMID- 29353753
TI  - Effect of dilute acid pretreatment of wild rice grass (Zizania latifolia) from
      Loktak Lake for enzymatic hydrolysis.
AB  - Zizania latifolia commonly known as wild rice grass which is available in huge
      quantities in Loktak Lake is a major concern as it occupies a large area of the
      Lake and causing a several environmental problems. The investigation of present
      study was to evaluate possibilities of using Zizania latifolia as feed stock for
      bioethanol production. The method involved the pretreatment with dilute acid or
      alkali followed by enzymatic hydrolysis with commercial cellulase. Acid
      pretreatment was performed with 10% biomass loading with different concentration
      of acids (0.4-2% w/v) and alkali (0.25-1.5% w/v). Maximum sugar release of 457
      mg/g was obtained from 10% biomass loading and 2% w/v of acids. Alkali
      pretreatment is not effective for this grass. Physicochemical characterization of
      untreated and treated biomass was carried out by XRD, FTIR, SEM and corresponding
      alterations in the chemical composition were also monitored. Results showed the
      feasibility of this grass as biofuel (bioethanol) feed stock and can be potential
      approach to address the sustainable utilization phumdis grasses of Loktak Lake
      for the production of value added product.

PMID- 29353754
TI  - Synergistic impact of sonic-tenside on biomass disintegration potential:
      Acidogenic and methane potential studies, kinetics and cost analytics.
AB  - An exploration into the symbiotic impact of sonic-tenside (SDBS - sodium dodecyl
      benzene sulfonate) on biomass disintegration potential and to reduce the energy
      consumption was studied. At optimized condition (specific energy input 9600 kJ/kg
      TS; SDBS dosage 0.07 g/g SS), higher percentage of biomass lysis and solids
      reduction (23.9% and 19.8%) was obtained in blended sonic-tenside disintegration
      (STD), than sonic disintegration (SD) (17.6% and 9.8%). The bioacidogenic
      potential (BAP) assay in terms of volatile fatty acids (VFA) production (722
      mg/L) was found to be higher for STD, in comparison to SD (350 mg/L). The impact
      of STD on anaerobic digestion was evident from its methane yield (0.239 g/g COD),
      higher than SD (0.182 g/g COD). A monetary evaluation of the present study
      provides a net gain of 2 USD/ton for STD, indicating the profitability of the
      technique.

PMID- 29353755
TI  - Enhanced reducing sugar production by saccharification of lignocellulosic
      biomass, Pennisetum species through cellulase from a newly isolated Aspergillus
      fumigatus.
AB  - A cellulose degrading fungus Aspergillus fumigatus (CWSF-7) isolated from
      decomposed lignocellulosic waste containing soil was found to produce high titer
      of cellulases. The optimum activity of CMCase and FPase were 1.9 U/mL and 0.9
      U/mL respectively while the highest protein concentration was found to be 1.2
      mg/mL. Saccharification of two Pennisetum grass varieties [dennanath (DG) and
      hybrid napier grass (HNG)] were optimized using partially purified CMCase and
      FPase in equal concentration, i.e. a ratios of 1:1 and further with addition of
      commercial xylanase using response surface methodology (RSM). The production of
      total reducing sugar (TRS) using isolated cellulase were 396.6 and 355.8 (mg/g),
      whereas further addition of xylanase had higher TRS titers of 478.7 and 483.3
      (mg/g) for DG and HNG respectively as evident from HPLC analysis. Further,
      characterization of the enzyme saccharified DG and HNG by SEM and ATR-FTIR
      revealed efficient hydrolysis of cellulose and partially hydrolysis of
      hemicellulose.

PMID- 29353756
TI  - Dry anaerobic co-digestion of food waste and cattle manure: Impact of total
      solids, substrate ratio and thermal pre treatment on methane yield and quality of
      biomanure.
AB  - The objective of the present study is to assess the impact of TS concentration,
      substrate mixing ratio (co digestion) and thermal pretreatment on biogas
      production, methane yield, VS reduction (%) and quality of biomanure through dry
      anaerobic digestion (DAD) of food waste (FW) and cattle manure (CM). Results
      divulged that the optimum methane yield and biomanure of 0.18 and 0.21 m3 CH4/(kg
      VS reduced) and 3.15 and 2.8 kg/kg waste was obtained from FW at TS of 25% and
      30% at an HRT of 41 and 31 days respectively whereas it was 0.32 and 0.43 m3
      CH4/(kg VS reduced) and 2.2 and 1.15 kg/kg waste from pretreated FW at an HRT of
      16 and 20 days correspondingly. Improvement of methane from 62 to 81% was
      obtained due to thermal pretreatment. The highest nutrient recovery in terms of
      N, P, K was found to be 5.14, 2.6 and 3.2 respectively.

PMID- 29353757
TI  - Cultivation of aerobic granular sludge in continuous flow under various selective
      pressure.
AB  - Formation of aerobic granular sludge was examined in a novel continuous flow
      configuration, at 20 +/- 1  degrees C. Synthetic proteinaceous wastewater with
      municipal primary effluent characteristics was used (i.e., COD = 370 +/- 30 mg/L;
      TN = 43 +/- 7 mg/L; and TP = 10 +/- 2 mg/L). Various levels of selective pressure
      were applied after inoculation with flocculent sludge (i.e., estimated velocity
      gradients during settling between 1 and 9 1/s). Impeller rpm of 15 and below
      generated floccular-granular biomass, while 20 rpm and above generated large
      granules with a filamentous population. Effluent soluble COD, total inorganic
      nitrogen, and phosphate of 25 +/- 7 mg/L, 11 +/- 1 mg/L, and 0.1 +/- 0.1 mg/L,
      respectively, were obtained. Observed yields were as low as 0.08-0.19 g-VSS/g-COD
      and whole sludge solids retention time was 18 +/- 1 d. Famine conditions
      developed for 90% of the total aerobic volume and >45 +/- 3% anaerobic substrate
      utilization was recorded. Aerobic granulation was demonstrated feasible under
      continuous flow providing adequate treatment with low biomass yields.

PMID- 29353758
TI  - Development of mixed bacterial cultures DAK11 capable for degrading mixture of
      polycyclic aromatic hydrocarbons (PAHs).
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent pollutants
      having mutagenic and carcinogenic properties. Microbial metabolism is an
      alternative approach for removal of PAHs from polluted environment. Mixed
      bacterial cultures DAK11 capable for degrading mixture of PAHs was developed from
      long term polluted marine sediments. DAK11 was able to degrade 500 mg/L of
      mixture of four PAHs and their degradation efficiency was enhanced by
      supplementing commercially available NPK fertilizer (0.1%, w/v). Anionic
      surfactant SDS has enhanced the degradation of PAHs, but DAK11 growth was
      inhibited in presence of cationic surfactant CTAB. Heavy metals have decreased
      the rate of degradation, while it was completely inhibited in the presence of
      Zn2+ and CrO42- (1mM). DAK11 was able to degrade PAHs in the presence of mono
      aromatic hydrocarbons, lubricant oil and diesel. Lower molecular weight aromatic
      and aliphatic compounds were identified using GC-MS during metabolism of mixture
      of PHAs.

PMID- 29353759
TI  - Optically stimulated Al2O3:C luminescence dosimeters for teletherapy: Hp(10)
      performance evaluation.
AB  - The performance of optically stimulated luminescence dosimeters (OSLDs, Al2O3:C)
      was evaluated in terms of the operational quantity of HP(10) in Co-60 external
      beam teletherapy unit. The reproducibility, signal depletion, and dose linearity
      of each dosimeter was investigated. For ten repeated readouts, each dosimeter
      exposed to 50mSv was found to be reproducible below 1.9 +/- 3% from the mean
      value, indicating good reader stability. Meanwhile, an average signal reduction
      of 0.5% per readout was found. The dose response revealed a good linearity within
      the dose range of 5-50mSv having nearly perfect regression line with R2 equals
      0.9992. The accuracy of the measured doses were evaluated in terms of operational
      quantity HP(10), wherein the trumpet curve method was used respecting the 1990
      International Commission on Radiological Protection (ICRP) standard. The accuracy
      of the overall measurements from all dosimeters was discerned to be within the
      trumpet curve and devoid of outlier. It is established that the achieved OSL
      Al2O3:C dosimeters are greatly reliable for equivalent dose assessment.

PMID- 29353760
TI  - Targeting the IL-17/IL-6 axis can alter growth of Chronic Lymphocytic Leukemia in
      vivo/in vitro.
AB  - The tumor microenvironment (TME) is critical to the longevity of tumor B cells in
      chronic lymphocytic leukemia (CLL). Bone marrow mesenchymal stem cells (BMMSCs)
      and the cytokines they produce including IL-6 are important components of the TME
      in CLL. We found BMMSCs supported the survival of CLL cells in vitro through an
      IL-6 dependent mechanism. IL-17 which induces IL-6 generation in a variety of
      cells increased production of IL-6 both in CLL cells and BMMSCs in vitro. In a
      xenograft CLL mouse model, BMMSCs and the culture supernatant of BMMSCs increased
      engraftment of CLL cells through an IL-6 mediated mechanism with human
      recombinant IL-6 showing similar effects in vivo. Human recombinant IL-17
      treatment also increased CLL engraftment in mice through an IL-6 mediated
      mechanism. Plasma of CLL patients showed elevated levels of both IL-6 and IL-17
      by ELISA compared with healthy controls, with levels of IL-6 linearly correlated
      with IL-17 levels. CLL patients requiring fludarabine based chemotherapy
      expressed higher levels of IL-6 and IL-17, while CLL patients with the lowest
      levels of IgA/IgM had higher levels of IL-6, but not IL-17. These data imply an
      important role for the IL-17/IL-6 axis in CLL which could be therapeutic targets.

PMID- 29353761
TI  - Theory of mind performances in first-episode schizophrenia patients: An 18-month
      follow-up study.
AB  - This study examined the change of Theory of Mind (ToM) performances in patients
      with first-episode schizophrenia over an 18-month period since illness onset. A
      computerised behavioural task was utilised to assess the affective and cognitive
      facets of visual-based ToM. Patients' ToM performances were standardised using
      the norms of gender-stratified, age- and IQ-matched controls. The results showed
      that schizophrenia patients exhibited poorer second-order affective and cognitive
      ToM at baseline, but their ToM ability improved after 18 months of follow-up. Our
      findings do not support a longitudinal dissociation of affective from cognitive
      ToM in schizophrenia.

PMID- 29353762
TI  - Alcohol use disorder and cognitive impairment in old age patients: A 6 months
      follow-up study in an outpatient unit in Barcelona.
AB  - There has been little research about deleterious effects, including cognitive
      impairment, related to hazardous long-term alcohol use in old adults. This study
      aims to assess cognitive decline in old patients with alcohol use disorder and
      changes in cognitive state at 6 months follow-up, achieving or not abstinence. A
      six-month follow-up study was conducted in an outpatient center in Barcelona on a
      sample of old adults (>=65 years old) who had hazardous alcohol use. The sample
      was compared with healthy volunteers adjusted for age, sex and years of
      education. A neuropsychological protocol was performed at baseline and after 6
      months follow-up covering four cognitive domains: attention, visuospatial
      abilities, memory and executive functions. Several domains were significant
      impaired at baseline: visual immediate and delayed recall, working memory,
      immediate verbal learning, total words learned, set switching and sustained
      attention. At 6 months reassessment, alcohol abstinence was achieved in 93.5% of
      patients and it was detected a trend towards improvement in direct mean scores of
      all cognitive areas, although it was not significant. The current study points
      out a cognitive impairment in many areas secondary to alcohol long-term hazardous
      use in old adults. A trend towards cognitive improvement after recovery was
      detected in most patients.

PMID- 29353764
TI  - The influence of time attitudes profile membership on mental well-being and
      psychosomatic symptomatology: A United Kingdom-based prospective study.
AB  - Mental well-being is of great importance for emotional, psychological and social
      functioning, particularly in adolescence, a period characterized by significant
      physical, social, and emotional changes. The extant literature examining the
      relationship between temporal attitudes and mental and psychosomatic health
      outcomes is increasing rapidly. Using Latent Transition Analysis (LTA) of
      Adolescent and Adult Time Inventory-Time Attitude Scale scores across three waves
      of data (N = 1667; 13-15 years; 42.0% female), we sought to examine the
      predictive power of time attitudes profile membership on mental well-being and
      psychosomatic symptomatology at distal wave four. Results indicated that staying
      in the Positive or Ambivalent profile was associated with more favorable distal
      outcomes at + 9 months; whereas staying in Negative or Moderately-Negative
      profile was strongly related to more somatic and psychological symptomatology,
      and lower mental well-being. Given the potential to modify time attitudes, these
      findings have several implications for interventions targeting adolescent mental
      and physical health.

PMID- 29353763
TI  - The Metacognitions about Gambling Questionnaire: Development and psychometric
      properties.
AB  - Recent research has suggested that metacognitions may play a role across the
      spectrum of addictive behaviours. The goal of our studies was to develop the
      first self-report scale of metacognitions about gambling. We conducted three
      studies with one community (n = 165) and two clinical (n = 110; n = 87) samples
      to test the structure and psychometric properties of the Metacognitions about
      Gambling Questionnaire and examined its capacity to prospectively predict
      severity of gambling. Findings supported a two factor solution consisting of
      positive and negative metacognitions about gambling. Internal consistency,
      predictive and divergent validity were acceptable. All the factors of the
      Metacognitions about Gambling Questionnaire correlated positively with gambling
      severity. Regression analyses showed that negative metacognitions about gambling
      were significantly associated to gambling severity over and above negative affect
      and gambling-specific cognitive distortions. Finally only gambling severity and
      negative metacognitions about gambling were significant prospective predictors of
      gambling severity as measured three months later. The Metacognitions about
      Gambling Questionnaire was shown to possess good psychometric properties, as well
      as predictive and divergent validity within the populations that were tested.

PMID- 29353765
TI  - Correlates of sedentary behaviour among adults with hazardous drinking habits in
      six low- and middle-income countries.
AB  - Sedentary behaviour is associated with poor mental health, diabetes and
      cardiovascular disease, all of which are a concern among hazardous drinkers.
      Little is known about sedentary behaviour and it's correlates in hazardous
      drinkers, particularly in low- and middle-income countries. We investigated
      correlates of sedentary behaviour among community-dwelling adults aged >=18 years
      with hazardous drinking patterns in six low- and middle-income countries. Cross
      sectional data were analyzed from the World Health Organization's Study on Global
      Ageing and Adult Health. Hazardous drinking was defined as consuming >7 (females)
      or >14 (males) standard drinks per week. Associations between time spent
      sedentary and a range of correlates were examined using multivariable linear and
      logistic regression. The mean time spent sedentary in 2142 individuals with
      hazardous drinking patterns (mean age = 45.7 years; 13% female) was 216+/
      135min/day. Nine percent (95%CI=6.1-13.2%) were sedentary for >=8h per day.
      Living in an urban setting and unemployment were strong sociodemographic
      correlates of being sedentary for >=8h per day. From a health-related
      perspective, weak grip strength, stroke and disability were associated with
      increasing time spent sedentary. The current data provides important guidance for
      future interventions across low- and middle-income countries to assist hazardous
      drinkers to reduce sedentary behaviour.

PMID- 29353766
TI  - Development and validation of Image Stimuli for Emotion Elicitation (ISEE): A
      novel affective pictorial system with test-retest repeatability.
AB  - The aim of this study was to develop a novel set of pictorial stimuli for emotion
      elicitation. The Image Stimuli for Emotion Elicitation (ISEE), are the first set
      of stimuli for which there was an unbiased initial selection method and with
      images specifically selected for high retest correlation coefficients and high
      agreement across time. In order to protect against a researcher's subjective bias
      in screening initial pictures, we crawled 10,696 images from the biggest image
      hosting website (Flickr.com) based on a computational selection method. In the
      initial screening study, participants rated stimuli twice for emotion elicitation
      across a 1-week interval and 1620 images were selected based on the number of
      ratings of participants and retest reliability of each picture. Using this set of
      stimuli, a second phase of the study was conducted, again having participants
      rate images twice with a 1-week interval, in which we found a total of 158 unique
      images that elicited various levels of emotionality with both good reliability
      and good agreement over time. The newly developed pictorial stimuli set is
      expected to facilitate cumulative science on human emotions.

PMID- 29353767
TI  - Acculturative stress and mental health among economically disadvantaged Spanish
      speaking Latinos in primary care: The role of anxiety sensitivity.
AB  - The present study examined the role of anxiety sensitivity in the relation
      between acculturative stress and mood and anxiety symptoms and disorders among
      Latinos seeking health services at a primary healthcare facility. Participants
      included 142 adult Latinos (86.6% female, Mage = 39.05 years, SD = 12.46%, and
      96.3% reported Spanish as their first language). Results indicated that
      acculturative stress was indirectly related to the number of mood and anxiety
      disorders, anxious arousal, social anxiety, and depressive symptoms through
      anxiety sensitivity. The observed effects were evident above and beyond the
      variance accounted for by gender, age, marital status, educational status,
      employment status, years living in the United States, and negative affectivity.
      Overall, the present findings suggest that there is merit in focusing further
      scientific attention on the interplay between acculturative stress and anxiety
      sensitivity to better understand and inform interventions to reduce
      anxiety/depressive vulnerability among Latinos in primary care.

PMID- 29353768
TI  - Leukocytes in peripheral blood in patients with bipolar disorder - Trait and
      state alterations and association with levels of cytokines and C-reactive
      protein.
AB  - Low-grade inflammation has been found in patients with bipolar disorder (BD), but
      rarely assessed using leukocyte counts and findings are limited by lack of
      control for confounding factors. As a result, it is unclear whether BD per se is
      associated with peripheral inflammation. We pooled populations from two studies
      using similar longitudinal designs, including 300 blood samples from a total of
      97 patients with BD and 133 blood samples from a total of 72 healthy control
      individuals (HC). Total leukocyte and neutrophil counts were measured together
      with interleukin (IL) - 6, IL-8, IL-18, tumor necrosis factor (TNF) - alpha and
      high sensitivity C-reactive protein (hsCRP). Adjusted for confounders, leukocyte
      counts were 23% higher and neutrophil counts were 30% higher in patients with BD
      compared with HC. There were no state-related differences in leukocyte or
      neutrophil counts. Lithium use, cigarette smoking as well as levels of IL-6, TNF
      alpha and hsCRP were positively associated with leukocyte and neutrophil counts.
      Due to confounding issues it cannot be concluded that differences were related to
      bipolar disorder per se. Future studies are recommended to include leukocytes as
      markers of low-grade inflammation and to include relevant confounders in
      statistical analyses.

PMID- 29353769
TI  - The impact of self-stigmatization on medication attitude in schizophrenia
      patients.
AB  - Negative attitudes towards medication in schizophrenia patients are one major
      factor contributing to non-adherence behavior. Besides, self-stigmatization
      represents another frequent and important obstacle in patients suffering from
      psychotic disorders. Here, we investigated possible associations between
      medication adherence attitude and the extent of self-stigmatization, while also
      exploring factors related to self-stigmatization. Sociodemographic
      characteristics, clinical variables, medication attitude and self-stigmatization
      were assessed among 81 subjects with schizophrenia or schizoaffective disorder.
      The cross-sectional data was then analyzed by multivariate analyses. A more
      positive attitude towards medication was predicted by better insight into
      illness, lower degree of self-stigmatization and good subjective knowledge about
      medication (adjusted R2 = 0.23). Furthermore, a higher level of self
      stigmatization was associated with lower subjective wellbeing, more severe
      depressive symptoms and male gender (adjusted R2 = 0.58). Other clinical
      variables had no additional predictive value for medication adherence attitude or
      the extent of self-stigmatization. Our findings support the notion that self
      stigmatization is an influential factor on medication attitude that should
      therefore be appreciated in clinical practice. Besides this, special emphasis
      should be taken on depressive symptoms and reduced wellbeing, especially in male
      patients, to lower the extent of self-stigmatization.

PMID- 29353770
TI  - Altered autonomic reactivity in Korean military soldiers with adjustment
      disorder.
AB  - Only few studies addressing the biological background of adjustment disorder (AD)
      exist. We examined the psychophysiological correlates indicative of autonomic
      regulation in AD. Heart rate variability (HRV), skin conductance, skin
      temperature, electromyography, and respiration were measured during serial stress
      tasks in 33 soldiers with AD and 60 healthy controls (HC). Patients with AD
      displayed lower relative power of high frequency (rHF) HRV and higher relative
      power of very low frequency (rVLF) HRV compared with HC at baseline. Inversely,
      the rHF of patients with AD remained higher and their rVLF remained lower
      compared with HC parameters after the single stress task, which suggests a
      reversed sympathovagal balance in AD. Mean heart rate and skin conductance
      increased during stress tasks in patients, although to a lesser extent than in
      HC. Skin temperature remained unchanged in all tasks in patients with AD. The
      tension of the frontalis muscle was higher in patients compared with HC from the
      second stress task onward. Thoracic breathing was more prevalent in patients with
      AD. Our study suggests altered autonomic reactivity in AD, which leads to a lack
      of sympathetic response to stress. We conclude that the distinctive biological
      mechanisms underlying AD are different from normal stress reactions.

PMID- 29353771
TI  - PTSD and depression in adult survivors of flood fury in Kashmir: The payoffs of
      social support.
AB  - Exposure to disasters such as floods predisposes individuals for psychological
      distress such as posttraumatic stress disorder (PTSD), depression, and anxiety.
      Researchers exploring the association between flood-exposure and psychopathology
      attempt to understand the conditions and mechanisms through which potential
      benefits may occur. One such potential factor that may contribute to resilience
      in the face of disaster is social support system. However, there is scarcity of
      researches concerning the protective effects of social support following floods,
      in adult samples. Thus, the present study examined the moderating and indirect
      effects of perceived social support from family and friends in the association
      between flood-exposure and symptoms of PTSD and depression. The study was a cross
      sectional in nature. Survey data were collected from 87 adult survivors of flood
      fury in Kashmir valley, aged 30-40. High level of family and friends' support
      reduced the association between flood-exposure and symptoms of PTSD and
      depression whereas a low level of such support enhanced this association. Results
      also suggested that family support carried a significant proportion of variance
      in predicting depression. Given the potential for negative mental health outcomes
      following natural disasters, efforts to enhance adults' social support may be
      especially important.

PMID- 29353772
TI  - The impact of development of atherosclerosis on delamination resistance of the
      thoracic aortic wall.
AB  - The aim of this work is to determine the impact of development of atherosclerosis
      on dissection of the human thoracic aorta on the basis of an analysis of the
      mechanical properties of the interfaces between its layers. The research material
      consisted of 17 pathologically unchanged aortae and 74 blood vessels with
      atherosclerotic lesions, which were classified according to the histological
      classification by Stary. The subject of the analysis were the interfaces between
      the adventitia and the media-intima complex (A-MIC) and between the intima and
      the media-adventitia complex (I-MAC). The mechanical properties of the above
      interfaces were determined by the peeling test in the longitudinal and
      circumferential directions. The results indicate that development of
      atherosclerosis reduces vessel wall resistance to delamination. The greatest risk
      of dissection occurs at stage IV of the disease. In this case, energy values are
      lower by about 28% for the I-MAC interface and by 39% for the A-MIC interface
      compared with normal tissues. Lower values of mean force and energy were obtained
      for the I-MAC interface, indicating that this interface is more susceptible to
      delamination. The mechanical properties of the A-MIC interfaces are directional.

PMID- 29353773
TI  - Energy absorption characteristics of bio-inspired honeycomb column thin-walled
      structure under impact loading.
AB  - Beetles have developed the elytra that are interesting and impressive strategy
      for thriving in their native environments. The elytra, although formed from
      simple biopolymer constituents, take on many effective designs. In present work,
      internal structure of elytra is discussed and three bionic structures named as
      the bio-inspired honeycomb column thin-walled structure (BHTS) are proposed. Then
      the crushing behavior and energy absorption characteristics of the BHTS under
      axial impact loading are investigated by numerical simulation. This study reveals
      not only the relationship between the adding mode and energy absorption
      characteristics, but also the influence of column diameter on the BHTS. The
      findings show that the BHTS represents a significant improvement over honeycomb
      structures and show potential applications in the field of protective equipment.

PMID- 29353774
TI  - Temporal and spatial variations of pressure within intervertebral disc nuclei.
AB  - Experimental and computational studies often presume that nuclei pulposi of non
      degenerated human lumbar discs function as fluid-filled cavities with single
      hydrostatic pressures throughout that vary neither with time nor location and
      orientation. Recent simultaneous measurements of the pressure at multiple
      locations within disc nuclei have however shown time-dependent and nonhomogeneous
      pressure distributions. This combined in vitro and in silico study aims to re
      examine the temporal and spatial variations of the pressure within disc nuclei
      with special focus on the effect of tissue hydration. After 20h of free swelling,
      effects of two preload magnitudes (0.06 and 0.28MPa) on nucleus pressure were
      investigated under 8h of constant preloads followed by 10 cycles of high-low
      loads each lasting 15min using 6 disc-bone bovine specimens. Changes in pressure
      at 3 different nucleus locations were recorded as surrogate measures of fluid
      flow within the discs. To identify the likely mechanisms observed in vitro, a
      finite element model of a human disc (L4-L5) was employed while simulating
      foregoing plus additional loading protocols. In vitro and computed results show a
      clear and substantial pressure gradient within the nucleus, especially early
      after the load application under higher loads and in more hydrated discs. The
      pressure reaches its maximum in the nucleus center reducing axially toward
      endplates and radially toward the nucleus-annulus interface. These cause pressure
      gradients that substantially diminish with time and at lower hydration levels.
      With time and as the pore pressure drops, the contribution of the nucleus bulk
      increases till it reaches equilibrium. The relative share of the annulus bulk in
      supporting the applied loads markedly increases not only with time but at higher
      loads and lower hydrations. The hydration state of the disc is hence crucial in
      the disc pressure distribution and internal response under various static-dynamic
      loads in vitro and in the replication of in vivo conditions.

PMID- 29353775
TI  - Mechanical wear and oxidative degradation analysis of retrieved ultra high
      molecular weight polyethylene acetabular cups.
AB  - The number of revision joint replacements has been increasing substantially over
      the last few years. Understanding their failure mechanism is extremely important
      for improving the design and material selection of current implants. This study
      includes ten retrieved and four new mildly cross-linked ultra-high molecular
      weight polyethylene (UHMWPE) acetabular liners. Among them, most of the
      prostheses (n = 5) were reported to be revised and replaced due to aseptic
      loosening, followed by painful joint (n = 2), dislocation (n = 1), intra
      articular ossification (n = 1), combination of wear (liner) and osteolysis (stem)
      (n=1). Surface deviations (wear, material inflation and roughness), oxidative
      degradation and change of material properties were measured using micro-computed
      tomography (micro-CT) scan, 3D laser scanning microscopy, raman spectroscopy and
      nanoindentation, respectively. Prostheses having eccentric worn areas had much
      higher linear wear rates (228.01 +/- 35.51um/year) compared to that of
      centrically worn prostheses (96.71 +/- 10.83um/year). Oxidation index (OI) showed
      similar trends to the surface penetration depth. Among them, sample 10 exhibited
      the highest OI across the contact area and the rim of the cup liner. It also had
      the lowest hardness/elasticity ratio. Overall, wear and creep, oxidative
      degradation and reduced hardness/elasticity ratio all contributed to the
      premature failure of the UHMWPE acetabular cup liners.

PMID- 29353776
TI  - Changes in Microcystis aeruginosa cell integrity and variation in microcystin-LR
      and proteins during Tanfloc flocculation and floc storage.
AB  - The objective of this study was to determine the influence of Tanfloc on
      Microcystis aeruginosa cell integrity, microcystin-LR (MC-LR), and proteins
      during flocculation and floc storage. The effects of Tanfloc addition, stirring,
      and floc storage time were considered to minimize cell damage and the release of
      MC-LR and proteins. Optimal flocculation conditions (Tanfloc dosage 10.42 mg L-1,
      rapid agitation for 0.36 min at 568.88 rpm and slow agitation for 14.14 min at
      12.1 rpm) were obtained using the response surface methodology. Up to 98.9% of
      the M. aeruginosa cells were removed intact at low Tanfloc dosage. During floc
      storage, Tanfloc initially protected the cells. After 8 d, large-scale cell lysis
      occurred because Tanfloc had substantially decomposed. Nevertheless, Tanfloc also
      extended the extracellular MC-LR and protein release time to 8 d. This delay
      ensured adequate time to decontaminate sludge containing the algae, thereby
      reducing the risk of secondary pollution. In addition, the low cost of Tanfloc
      facilitates its widespread application in the management of harmful algal blooms.

PMID- 29353777
TI  - Spatiotemporal variation of domestic biomass burning emissions in rural China
      based on a new estimation of fuel consumption.
AB  - Domestic biomass burning (DBB) influences both indoor and outdoor air quality due
      to the multiple pollutants released during incomplete and inefficient combustion.
      The emissions are not well quantified because of insufficient information, which
      were the key parameters related to fuel consumption estimation, such as province-
      and year-specific percentage of domestic straw burning (Pstraw) and firewood
      consumption (Fc). In this study, we established the quantitative relationship
      between rural-related socioeconomic parameters (e.g., rural per-capita income and
      rural Engel's coefficient) and Pstraw/Fc. DBB emissions, including 12 crop straw
      types and firewood for 12 kinds of pollutants in China during the period 1995
      2014, were estimated based on fuel-specific emission factors and detailed fuel
      consumption data. The results revealed that the national emissions generally
      increased initially and then decreased with the turning point around 2007-2008.
      Firewood burning was the major source of the NH3 and BC emissions; straw burning
      contributed more to SO2, NMVOC, CO, OC, and CH4 emissions; while the major
      contributor changed from firewood to domestic straw burning for NOx, PM10, PM2.5,
      CO2, and Hg emissions. The emission trends varied among the 31 provinces. The
      major agricultural regions of north-eastern, central, and south-western China
      were always characterized by high emissions. The spatial variation mainly
      occurred in the northeast and north China (increase), and central-south and
      coastal regions of China (decrease).

PMID- 29353778
TI  - Estimating the burden of lung cancer and the efficiency of home radon mitigation
      systems in some Canadian provinces.
AB  - : Lung cancer (LC) is the leading cause of death of cancer in Canada in both men
      and women, and indoor radon is the second leading cause of LC after tobacco
      smoking. The Population Attributable Risk (PAR) is used to assess radon exposure
      risk. In this work we estimate the burden of LC in some Canadian provinces. We
      use the PAR to identify the radon levels responsible for most LC cases. Finally,
      we use the PAR function of the two variables, radon action and target levels, to
      search for a possible optimal mitigation program. METHODS: The LC burden for
      Ontario, Alberta, Manitoba, Quebec and British Columbia was estimated using
      provincial radon and mortality data. Then the PAR and LC cases for these
      provinces were estimated over the period 2006-2009 at different given indoor
      radon exposure levels. Finally, the PAR function when radon action levels and
      radon target levels are variables was analyzed. RESULTS: The highest burden of LC
      in 2006-2009 was in Ontario and Quebec. During the period 2006-2009, 6% of houses
      in Ontario, 9% of houses in Alberta, 19% of houses in Manitoba, 7% of houses in
      Quebec, and 5% of houses in British Columbia had radon levels higher than 200
      Bq/m3 and were responsible about 913, 211, 260, 972, and 258 lives, respectively.
      Radon mitigation programs could have prevented these LC cases. The BEIR VI
      assumption for the United States (US) population, 95% of LC deaths in men and 90%
      of LC deaths in women are Ever-Smokers (ES), can be applied to the Canadian
      population. The PAR is a linear function in the target radon value with an
      estimated slope of 0.0001 for Ontario, Alberta, Quebec and British Columbia, and
      0.0004 for Manitoba. The PAR is almost a square root function in the radon action
      level. The PAR is sensitive to changes in the radon mitigation program and as
      such, any improvement is a worthwhile investment.

PMID- 29353779
TI  - Trace metals and macroelements in mussels from Chinese coastal waters: National
      spatial patterns and normalization.
AB  - Metal contamination is one of the most ubiquitous and complex problems in the
      Chinese coastal environment. To explore the large-scale spatial patterns of
      bioavailable metals, we sampled three major mussels, including 784 blue mussels
      (Mytilus edulis Linnaeus, 1758) of 14 sites, 224 hard-shelled mussels (Mytilus
      unguiculatus Valenciennes, 1858) of 4 sites, and 392 green mussels (Perna viridis
      (Linnaeus, 1758)) of 7 sites, ranging from temperate to tropical coastlines of
      China, during August and September 2015. The concentrations of macroelements (Na,
      K, Ca, Mg, and P) and toxic trace metals (Ag, Cd, Cr, Cu, Ni, Pb, Ti, and Zn) in
      the mussel's whole soft tissues were determined. Among the four Chinese coastal
      basins, Cd, Ti and Cr in the mussel tissues were the highest at Bohai Sea (BS)
      and Yellow Sea (YS), and Cu, Ni, Pb and Ag in the mussel tissues were the highest
      at East China Sea (ECS) and South China Sea (SCS). Zinc concentrations in mussels
      from YS were significantly higher than those from the other regions. Given the
      variability of environmental conditions such as salinity and nutrients, we
      further normalized the measured tissue metal concentrations with tissue Na and P
      levels. After Na normalization as the salinity proxy, the variability of Cd, Cu,
      Zn, Ag, and Ni was reduced. Trace elements accumulation in the mussel tissues was
      significantly related to both macroelements (Na or P) and body dry weight. The
      present study demonstrated that nonlinear optimization of different elements was
      necessary in assessing metal bioaccumulation patterns in marine mussels at a
      large spatial scale.

PMID- 29353780
TI  - Development of a QuEChERS method for simultaneous analysis of antibiotics in
      carcasses for supplementary feeding of endangered vultures.
AB  - Antibiotics have been beneficial for human and animal health. However, an
      excessive use in livestock and a deficient management of the carcasses can lead
      to adverse effects in the scavengers that ingest them, especially in
      "supplementary feeding sites" (SFS). The aim of this study was to assess the
      potential risk of exposure to antibiotics for an endangered population of
      Cinereous vultures (Aegypius monachus) from southeastern Portugal. Hence, a multi
      residue method based on QuEChERs was adapted and validated to analyse, in small
      volumes of tissues, the most frequent antibiotics used in livestock. The method
      was applied to 87 samples of liver, muscle and kidney from 7 goats and 25 sheep
      disposed in SFS. According to questionnaires to farmers, the animals had not been
      treated with antibiotics, but analyses showed residues in 29% of the samples.
      Antibiotics were more frequent in goats (42.9%) than in sheep (24.2%), and
      oxytetracycline and trimethoprim were the most common (both 13.8%).
      Oxytetracycline, the most common antibiotic for livestock in Portugal, showed the
      highest concentration (1452.68 ng g-1). To our knowledge, this is the first study
      of presence of antibiotics in carrion from SFS. The concentrations of antibiotics
      in carrion do not seem to pose a risk of acute intoxication for adult Cinereous
      vultures. However, subtle and likely chronic exposure with unknown health
      consequences may occur, which requires more research. Moreover, the results of
      this first study can be used in future studies to assess the risk for avian
      scavengers.

PMID- 29353781
TI  - Age-dependent changes in essential elements and oxidative stress biomarkers in
      blood of red deer and vulnerability to nutritional deficiencies.
AB  - Changes in the concentration of circulating essential elements in animals over
      life may be indicative of periods of vulnerability to deficiencies and associated
      diseases. Here we studied age-related variations in essential elements (Se, Cu,
      Zn and Mn) and some selected oxidative stress biomarkers (GPx, SOD, vitamin A and
      vitamin E) in blood of an Iberian red deer (Cervus elaphus hispanicus) population
      living in semicaptive conditions. Animals during their first year of life showed
      to be especially vulnerable to suffer Se- and Cu-related diseases and disorders.
      Older female deer had lower blood levels of Zn and Mn, which was accompanied by a
      lower blood SOD activity. On the contrary, GPx blood activity was elevated in
      older deer, which may help to compensate the reduction of other antioxidants with
      during aging. Age-related changes in GPx and SOD and their positive relationships
      with the essential elements suggest that the observed nutritional deficiencies at
      certain age stages may have a detrimental effect on the antioxidant system,
      increasing the risk of oxidative stress. Thus, the biomarkers used in the present
      study may be important tools for the subclinical diagnosis of nutritional
      disorders and diseases related to the generation of oxidative stress in both
      domestic and wild ungulates.

PMID- 29353782
TI  - Hydrochemical characteristics of ground ice in permafrost regions of the Qinghai
      Tibet Plateau.
AB  - Ground ice is a distinctive feature of permafrost terrain. The vertical
      distribution and factors controlling the hydrochemistry of ground ice are
      important for studying soil moisture and salt migration during the freeze-thaw
      process in soil. These factors are also important components of hydrological
      cycles in cold regions. The hydrochemical characteristics of ground ice on the
      Qinghai-Tibetan Plateau (QTP) are not well known. We examined the characteristics
      of ground ice hydrochemistry using data from 9 soil profiles in permafrost
      regions of the central QTP. The isotopes and anion concentrations of subsurface
      water on the QTP were higher than those in Arctic polygonal ground regions. The
      spatial distribution of anions was complex. Well-developed hydrochemical depth
      gradients occurred within the soil profile. Isotopes decreased and anions
      increased with depth, suggesting general vertical patterns of soil hydrochemistry
      across different permafrost regions. Cl- and SO42- concentrations in soil water
      increased with depth, while NO3- concentration did not change with depth. Freeze
      out fractionation, self-purification, and desalination greatly impact soil
      hydrochemistry. The major factors controlling variation of soil water chemistry
      were soil moisture, air temperature, and active layer thickness. The results
      could provide a framework for understanding ground ice origins and the moisture
      and salt migration pathways in the context of permafrost changes. This
      information could be useful in developing process-based permafrost hydrologic
      models.

PMID- 29353783
TI  - The prevalence of multidrug-resistant Aeromonas spp. in the municipal wastewater
      system and their dissemination in the environment.
AB  - The objective of this study was to identify the determinants of antibiotic
      resistance and virulence of Aeromonas spp. isolated from treated wastewater (WW)
      and from samples of river water collected upstream (URW) and downstream (DRW)
      from the effluent discharge point. The resistance of Aeromonas spp. to
      antibiotics that are widely used in human and veterinary medicine, including beta
      lactams, tetracyclines, glycylcyclines, fluoroquinolones, aminoglycosides and
      sulfamethoxazole-trimethoprim, was analyzed by disk diffusion method. The
      prevalence of hemolysins, aerolysins (virulence factors) and integrase genes was
      determined. A total of 83 Aeromonas spp. strains were selected from the isolates
      obtained from river water and wastewater samples. The highest percentage (81.8%)
      of multidrug-resistant isolates was noted in DRW samples. The analyzed isolates
      were most frequently resistant to beta-lactams, tetracyclines and
      aminoglycosides, whereas resistance to glycylcyclines was least common. Isolates
      resistant to beta-lactams most frequently harbored blaTEM and blaOXA genes. The
      group of genes encoding resistance to tetracyclines was most frequently
      represented by tet(E) and tet(O). Genes encoding virulence ahh1 (heat-labile
      hemolysin) or integrase intI1 occurred more frequently in the strains isolated
      from DRW than URW. An analysis of genetic relatedness revealed two main clusters 
      one with closely related WW and DRW isolates and one with less related isolates
      from all analyzed samples. The results of this study indicate that regardless of
      the applied treatment, municipal sewage may be a reservoir of antibiotic
      resistant bacteria, antibiotic resistance and virulence genes and that treated
      water can contaminate other environmental domains.

PMID- 29353784
TI  - On the ecological relevance of landscape mapping and its application in the
      spatial planning of very large marine protected areas.
AB  - In recent years very large marine protected areas (VLMPAs) have become the
      dominant form of spatial protection in the marine environment. Whilst seen as a
      holistic and geopolitically achievable approach to conservation, there is
      currently a mismatch between the size of VLMPAs, and the data available to
      underpin their establishment and inform on their management. Habitat mapping has
      increasingly been adopted as a means of addressing paucity in biological data,
      through use of environmental proxies to estimate species and community
      distribution. Small-scale studies have demonstrated environmental-biological
      links in marine systems. Such links, however, are rarely demonstrated across
      larger spatial scales in the benthic environment. As such, the utility of habitat
      mapping as an effective approach to the ecosystem-based management of VLMPAs
      remains, thus far, largely undetermined. The aim of this study was to assess the
      ecological relevance of broadscale landscape mapping. Specifically we test the
      relationship between broad-scale marine landscapes and the structure of their
      benthic faunal communities. We focussed our work at the sub-Antarctic island of
      South Georgia, site of one of the largest MPAs in the world. We demonstrate a
      statistically significant relationship between environmentally derived landscape
      mapping clusters, and the composition of presence-only species data from the
      region. To demonstrate this relationship required specific re-sampling of
      historical species occurrence data to balance biological rarity, biological
      cosmopolitism, range-restricted sampling and fine-scale heterogeneity between
      sampling stations. The relationship reveals a distinct biological signature in
      the faunal composition of individual landscapes, attributing ecological relevance
      to South Georgia's environmentally derived marine landscape map. We argue
      therefore, that landscape mapping represents an effective framework for ensuring
      representative protection of habitats in management plans. Such scientific
      underpinning of marine spatial planning is critical in balancing the needs of
      multiple stakeholders whilst maximising conservation payoff.

PMID- 29353785
TI  - Experimental study of biomass gasification with oxygen-enriched air in fluidized
      bed gasifier.
AB  - Considering the universality, renewability and cleanness of biomass, an
      experimental research is carried out using rice straw in a two-stage fluidized
      bed. The experimental analysis identified the relevant parameters in the
      operation of the two-stage fluidized bed to investigate the properties of biomass
      enriched air gasification. Results show that higher gasification temperature is
      conducive to enhance the gasification performance. An increasing ER is shown to
      go against adding gas heat value. When oxygen concentration increases from 21% to
      45%, the gas heating value increases from 4.00MJ/kg to 5.24MJ/kg and the
      gasification efficiency increases from 29.60% to 33.59%, which shows higher
      oxygen concentration is conducive to higher quality gas and higher gasification
      efficiency. A secondary oxygen injection leads to reduction of tar concentration
      from 15.78g/Nm3 to 10.24g/Nm3. The optimal secondary oxygen ratio is about
      33.00%. When the secondary oxygen ratio increased to 46.86%, monocyclic aromatics
      reduced from 28.17% to 19.65% and PAHs increased from 34.97% to 44.05%, leading
      to the increase aromatization of tar.

PMID- 29353786
TI  - A macrophysiology approach to watershed science and management.
AB  - Freshwaters are among the most imperiled ecosystems on the planet such that much
      effort is expended on environmental monitoring to support the management of these
      systems. Many traditional monitoring efforts focus on abiotic characterization of
      water quantity or quality and/or indices of biotic integrity that focus on higher
      scale population or community level metrics such as abundance or diversity.
      However, these indicators may take time to manifest in degraded systems and delay
      the identification and restoration of these systems. Physiological indicators
      manifest rapidly and portend oncoming changes in populations that can hasten
      restoration and facilitate preventative medicine for degraded habitats.
      Therefore, assessing freshwater ecosystem integrity using physiological
      indicators of health is a promising tool to improve freshwater monitoring and
      restoration. Here, we discuss the value of using comparative, longitudinal
      physiological data collected at a broad spatial (i.e. watershed) scale (i.e.
      macrophysiology) as a tool for monitoring aquatic ecosystem health within and
      among local watersheds to develop timely and effective management plans. There
      are emerging tools and techniques available for rapid, cost-effective, and non
      lethal physiological sampling and we discuss how these can be integrated into
      management using fish as sentinel indicators in freshwater. Although many
      examples of this approach are relatively recent, we foresee increasing use of
      macrophysiology in monitoring, and advocate for the development of more standard
      tools for consistent and reliable assessment.

PMID- 29353788
TI  - Fabrication of spherical biochar by a two-step thermal process from waste potato
      peel.
AB  - The aim of this study was to develop a new approach for the preparation of
      spherical biochar (SBC) by employing a two-step thermal technology to potato peel
      waste (PPW). Potato starch (PS), as a carbon-rich material with microscale
      spherical shape, was separated from PPW as a precursor to synthesizing SBC. The
      synthesis process comprised (1) pre-oxidization (preheating under air) of PS at
      220  degrees C and (2) subsequent pyrolysis of the pretreated sample at 700 
      degrees C. Results showed that the produced SBC successfully retained the
      original PS morphology and that pre-oxidization was the key for its shape
      maintenance, as it reduced surface tension and enhanced structural stability. The
      SBC possessed excellent chemical inertness (high aromaticity) and uniform
      particle size (10-30 MUm). Zero-cost waste material with a facile and easy-to
      control process allows the method to be readily scalable for industrialization,
      while offering a new perspective on the full use of PPW.

PMID- 29353787
TI  - Maternal urinary triclosan level, gestational diabetes mellitus and birth weight
      in Chinese women.
AB  - Triclosan (TCS) is an antibacterial chemical widely used in personal-care
      products and an endocrine disruptor. While TCS exposure is associated with
      insulin resistance and metabolic disorders in animals, few studies have assessed
      its effect on the risk of gestational diabetes mellitus (GDM) in humans. This
      study aimed to explore whether maternal urinary TCS level is associated with the
      risk of GDM and infant birthweight. We examined 620 pregnant women from Shanghai,
      China in 2012-2013. Urinary TCS level was measured with high-performance liquid
      chromatography-tandem mass spectrometry (HPLC-MS/MS), and categorized into high,
      medium and low in tertiles. GDM was defined based on recommendation of
      International Association of Diabetes and Pregnancy Study Groups (IADPSG). The
      GDM rate was 12.7%. TCS was detectable (>=0.1 ng/mL) in 97.9% women (median 2.7
      ng/mL). There was a positive, but statistically non-significant association
      between urinary TCS levels and GDM (adjusted odds ratio 1.17; 95%CI: 0.99, 1.39,
      with each unit increase of log (TCS) ng/mL) with adjustment for urinary
      creatinine, maternal age, education, passive smoking, parity and prepregnancy BMI
      categories. 48.1% of infants were females. Birthweight was 122.8 g higher (95%
      CI: 13.9, 231.6 g) for female infants of women in high TCS (median 13.3 ng/mL)
      versus low TCS (median 0.77 ng/mL), with adjustment for urinary creatinine,
      prepregnancy BMI, GDM and other confounders. No association was found between
      maternal TCS and birthweight in male infants. These results suggested the
      potential for TCS to be associated with increased risk of GDM and a gender
      specific association with higher birthweight among female infants in a population
      with widespread but moderate exposure to TCS.

PMID- 29353789
TI  - Value of irrigation water usage in South Florida agriculture.
AB  - This study estimates economic loss from South Florida croplands when usage of
      agricultural irrigation water is altered. In South Florida, 78% of the total
      value of farm products sold is comprised of cropland products. The majority of
      Florida citrus and sugarcane are produced in the area, and agricultural
      irrigation was the largest sector of water use in 2010, followed by public water
      supply. The Florida Department of Environmental Protection announced in December
      2012 that traditional sources of fresh groundwater will have difficulty meeting
      all of the additional demands by 2030. A shortage of water will impose
      significant damage to the rural and agriculture economy in Florida, which may
      lead to higher prices and costs for consumers to purchase citrus or other Florida
      agriculture products. This paper presents a methodology for estimating economic
      loss when usage of irrigation water is altered, and examines economic values of
      irrigation water use for South Florida cropland. The efficient allocation of
      irrigation water across South Florida cropland is also investigated in order to
      reduce economic cost to the South Florida agricultural sector.

PMID- 29353790
TI  - Remediation of chlorinated ethenes in fractured sandstone by natural and enhanced
      biotic and abiotic processes: A crushed rock microcosm study.
AB  - Biostimulation was identified as a potential technology to treat a fractured
      sandstone aquifer contaminated with trichloroethene (TCE) and cis-1,2
      dichloroethene (cis-DCE). Most of the mass of TCE and cis-DCE resides within the
      rock matrix and strategies to restore groundwater to pre-existing conditions are
      severely limited by back diffusion. A microcosm study using crushed rock and
      groundwater from the site was performed to assess biostimulation and natural
      attenuation. Lactate, hydrogen release compound(r) (HRC), and emulsified
      vegetable oil (EVO) significantly increased the rate of TCE reduction to cis-DCE.
      Lactate also stimulated dechlorination of cis-DCE to vinyl chloride (VC) and
      ethene, suggesting the presence of indigenous Dehalococcoides. Illumina
      sequencing and qPCR analyses suggest that reductive dechlorination of TCE to cis
      DCE is mediated by Geobacter spp. while Dehalococcoides spp. perform reduction of
      cis-DCE to VC and ethene. The rate of VC reduction to ethene was much slower than
      the reduction of TCE to cis-DCE and cis-DCE to VC, indicating the indigenous
      Dehalococcoides perform the final step co-metabolically. This was confirmed in
      enrichment cultures fed with only VC. Consequently, biostimulation may create an
      elevated risk due to transient accumulation of VC. Abiotic transformation of TCE
      and cis-DCE was observed based on accumulation of 14C-labeled products from 14C
      TCE and 14C-cis-DCE, as well as enrichment in delta13C-cis-DCE in the absence of
      reductive dechlorination. Based on accumulation rates for 14C-products in
      unamended microcosms, pseudo-first-order rates for abiotic transformation were
      0.038 yr-1 for TCE and 0.044 yr-1 for cis-DCE. These rates within the rock matrix
      may be sufficient to support natural attenuation in this diffusion controlled
      system.

PMID- 29353791
TI  - Characteristics and sources of aerosol pollution at a polluted rural site
      southwest in Beijing, China.
AB  - Annual average PM2.5 concentration in south Beijing was 30% and 40% higher than
      the whole Beijing city in 2015 and 2016, respectively. Few studies have been
      conducted to investigate what leads to the characteristics and sources of heavy
      pollution in the south rural area of Beijing. This study conducted an observation
      with Aerosol Chemical Speciation Monitor (ACSM) at a southwest rural site
      (Liulihe) in Beijing during 2014-2016, to investigate the seasonal aerosol
      characteristics and their sources. Positive matrix factorization (PMF) algorithm
      was used to distinguish different components of organic aerosol measured by ACSM.
      Biomass burning is an important pollution source, mainly due to the open burning
      after harvest season in autumn, regional transport in spring, and local
      residential biofuel use in winter. Coal consumption is the largest primary
      organic aerosol source in winter. Heavy duty diesel trucks contributed
      significantly to organic aerosol at night-time in the rural area. Results of this
      study show residential solid fuel burning is the most important source of aerosol
      pollution in the rural area of Beijing and the results focusing on urban Beijing
      might have underestimate the contribution from residential emissions in the
      Beijing-Tianjin-Hebei region.

PMID- 29353792
TI  - Bioavailability of potentially toxic elements in soil-grapevine (leaf, skin, pulp
      and seed) system and environmental and health risk assessment.
AB  - Monitoring of potentially toxic elements in agricultural soil represents the
      first measure of caution regarding food safety, while research into element
      bioavailability should be a step forward in understanding the element
      transportation chain. This study was conducted in the grapevine growing area
      ("Oplenac Wine Route") for investigating element bioavailability in the soil
      grapevine system accompanied by an assessment of the ecological implications and
      human health risk. Single extraction procedures (CH3COOH, Na2EDTA, CaCl2, NH4NO3
      and deionised H2O) and digestion were performed to estimate the bioavailability
      of 22 elements (Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, K, Li, Mg, Mn, Na, Ni,
      Pb, Sb, Sr, V and Zn) from the topsoil (0-30 cm) and subsoil (30-60 cm) to the
      grapevine parts (leaf, skin, pulp and seed) and wine. The extractants were
      effective comparing to the pseudo-total concentrations in following order Na2EDTA
      ? CH3COOH ? NH4NO3 ? CaCl2, H2O 2 h and 16 h. The most suitable extractants for
      assessing the bioavailability of the elements from the soil to the grapevine
      parts were CaCl2, NH4NO3 and Na2EDTA, but deionised H2O could be suitable, as
      well. The results showed that Ba was the most bioavailable element in the soil
      grapevine system. Contamination factor implied a moderate contamination (1 < CF <
      3) of the soil. The concentrations of Cr, Ni and Cd in the soil were above the
      maximum allowed concentrations. According to the biological accumulation
      coefficient (BAC), the grape seeds and grapevine leaves mostly accumulated Cu and
      Zn from the soil, respectively. Based on ratio factor (RF > 1), the influence of
      atmospheric deposition on the aerial grapevine parts (leaves and grape skin) was
      observed. Nevertheless, low adverse health risk effects (HI < 1 and R <= 1 * 10
      6) were estimated for farmers and grape and wine consumers.

PMID- 29353793
TI  - Health and economic benefits of building ventilation interventions for reducing
      indoor PM2.5 exposure from both indoor and outdoor origins in urban Beijing,
      China.
AB  - China is confronted with serious PM2.5 pollution, especially in the capital city
      of Beijing. Exposure to PM2.5 could lead to various negative health impacts
      including premature mortality. As people spend most of their time indoors, the
      indoor exposure to PM2.5 from both indoor and outdoor origins constitutes the
      majority of personal exposure to PM2.5 pollution. Different building
      interventions have been introduced to mitigate indoor PM2.5 exposure, but always
      at the cost of energy expenditure. In this study, the health and economic
      benefits of different ventilation intervention strategies for reducing indoor
      PM2.5 exposure are modeled using a representative urban residence in Beijing,
      with consideration of different indoor PM2.5 emission strengths and outdoor
      pollution. Our modeling results show that the increase of envelope air-tightness
      can achieve significant economic benefits when indoor PM2.5 emissions are absent;
      however, if an indoor PM2.5 source is present, the benefits only increase
      slightly in mechanically ventilated buildings, but may show negative benefit
      without mechanical ventilation. Installing mechanical ventilation in Beijing can
      achieve annual economic benefits ranging from 200yuan/capita to 800yuan/capita if
      indoor PM2.5 sources exist. If there is no indoor emission, the annual benefits
      above 200yuan/capita can be achieved only when the PM2.5 filtration efficiency is
      no <90% and the envelope air-tightness is above Chinese National Standard Level
      7. Introducing mechanical ventilation with low PM2.5 filtration efficiency to
      current residences in urban Beijing will increase the indoor PM2.5 exposure and
      result in excess costs to the residents.

PMID- 29353794
TI  - The application of a high-density street-level air temperature observation
      network (HiSAN): Dynamic variation characteristics of urban heat island in
      Tainan, Taiwan.
AB  - The effects of urban heat island (UHI) have recently become a crucial issue. This
      study utilized a high-density street-level air temperature observation network
      (HiSAN) to understand the UHI characteristics in Tainan City. A total of 100
      measurement points were established throughout the city. The average distance
      between two neighboring measuring points was 1.9 km in rural areas and 0.8 km in
      metropolitan areas. The UHI caused a temperature differences of at least 3 
      degrees C in each month over the study period, and the UHI's centric point moved
      from west to east during the day and from east to west at night, mainly because
      of the physical effects of the different urban environment including location and
      the impermeable surface area (ISA), total floor area, and sky view factor in
      urban areas. The results also indicated that factors such as ISA and distance to
      the coast had the strongest influence on thermal conditions at various times,
      especially in the areas far from the coast during the hot season. This was mainly
      because of differences in how heat was retained over the study area. The HiSAN
      method can be used by urban planners, architects, and policymakers to mitigate
      the thermal stresses caused by complex urban environments.

PMID- 29353795
TI  - Identifying outdoor thermal risk areas and evaluation of future thermal comfort
      concerning shading orientation in a traditional settlement.
AB  - The outdoor thermal environment is expected to be deteriorated under climate
      change. An approach of risk identification including assessment from aspects of
      thermal stress effect, people's exposure, and local's vulnerability were adopted
      to study a hot-and-humid traditional rural community located at Tainan, Taiwan.
      Layers of each aspect were either constructed by in-situ measurements or
      simulations. To evaluate the future thermal comfort changes by simulations, the
      prerequisite hourly climate data of three future time slices were produced.
      Prognostic simulation model, ENVI-met, in combination with diagnostic model,
      RayMan, were respectively used for identifying current spatial distribution of
      thermal stress and for assessing the future thermal comfort changes. High thermal
      risk area was identified by superimposing layers of hazard, exposure and
      vulnerability. It revealed that because of the tourists' vulnerability to adapt
      local climate and the inflexibleness of choosing visiting time, it exhibited a
      high thermal stress at the Main Courtyard where its thermal comfort conditions
      will be deteriorated due to climate change. Furthermore, the thermal comfort
      conditions in various shading orientation were analyzed based on the changing
      climate in three future time slices, i.e. 2011-2040, 2041-2070, and 2071-2100.
      The results show the area with shading in the East and West side is more comfort
      than in the North side. In hot season, shading in the West side contributes less
      PET increasing, especially in the afternoon period. The severest overheat problem
      (the physiological equivalent temperature, PET>40 degrees C) at the Main
      Courtyard will increase from current 10% to 28% in 2071-2100 in terms of
      overheating occurrence frequency. The results of this study can be used as the
      guidelines for environment analysis before planning or redesign community.

PMID- 29353796
TI  - Associations between arsenic in drinking water and occurrence of end-stage renal
      disease with modifications by comorbidities: A nationwide population-based study
      in Taiwan.
AB  - Arsenic may affect the function of proximal convoluted tubules and glomeruli, but
      epidemiological data on the association between arsenic ingestion and end-stage
      renal disease (ESRD) are limited. Therefore, we conducted a nationwide population
      based study in Taiwan, where the incidence of ESRD is the highest in the world,
      to study the potential association. Using the National Health Insurance Database
      in Taiwan, we constructed a cohort of 362,505 members with age>=40years in 1998.
      We identified patients of ESRD newly diagnosed between January 1, 1998 and
      December 31, 2010 and performed Cox proportional hazard regressions to identify
      risk factors for ESRD and evaluate their effects. Arsenic levels in drinking
      water were assessed on the basis of a nationwide census survey conducted by the
      government, of which measurement reports were available for 311 townships. We
      identified 5442 new patient of ESRD during the study period and found that
      residents of areas with arsenic levels>=50MUg/L in the drinking water had a
      hazard ratio (HR) of 1.14 (95% confidence interval [CI]: 1.08-1.21) for ESRD.
      After adjusting for sex, age, income, and comorbidities, we found an adjusted HR
      of 1.12 (95% CI: 1.06-1.19), which was still statistically significant.
      Furthermore, the effect was modified by comorbidities, with more prominent
      effects on patients with less than three comorbidities (adjusted HR=1.51; 95% CI:
      1.22-1.86 for low comorbidity score). In conclusion, a high arsenic level in
      drinking water was a risk factor for ESRD, independent of other documented risk
      factors. Reducing high-risk comorbidities in patients with early-stage renal
      dysfunction is important for slowing the progression of the disease to ESRD, even
      in the endemic area of arsenic exposure.

PMID- 29353798
TI  - Role of autophagy in environmental neurotoxicity.
AB  - Human exposure to neurotoxic pollutants (e.g. metals, pesticides and other
      chemicals) is recognized as a key risk factor in the pathogenesis of
      neurodegenerative disorders. Emerging evidence indicates that an alteration in
      autophagic pathways may be correlated with the onset of the neurotoxicity
      resulting from chronic exposure to these pollutants. In fact, autophagy is a
      natural process that permits to preserving cell homeostasis, through the seizure
      and degradation of the cytosolic damaged elements. However, when an excessive
      level of intracellular damage is reached, the autophagic process may also induce
      cell death. A correct modulation of specific stages of autophagy is important to
      maintain the correct balance in the organism. In this review, we highlight the
      critical role that autophagy plays in neurotoxicity induced by the most common
      classes of environmental contaminants. The understanding of this mechanism may be
      helpful to discover a potential therapeutic strategy to reduce side effects
      induced by these compounds.

PMID- 29353797
TI  - Source tagging modeling study of regional contributions to acid rain in summer
      over Liaoning Province, Northeastern China.
AB  - Strong acid rain was recently observed over Northeastern China, particularly in
      summer in Liaoning Province where alkaline dust largely neutralized acids in the
      past. This seems to be related to the regional transboundary pollution and poses
      new challenges in acid rain control scheme in China. In order to delve into the
      regional transport impact, and quantify its potential contributions to such an
      "eruption" of acid rain over Liaoning, this paper employs an online source
      tagging model in coupling with the Nested Air Quality Prediction Modeling System
      (NAQPMS). Validation of predictions shows the model capability in reproducing key
      meteorological and chemical features. Acid concentration over Liaoning is more
      pronounced in August (average of 0.087 mg/m3) with strong pollutant import from
      regional sources against significant depletion of basic species. Seasonal mean
      contributions from regional sources are assessed at both lower and upper boundary
      layers to elucidate the main pathways of the impact of regional sources on acid
      concentration over Liaoning. At the upper layer (1.2 km), regional sources
      contribute to acid concentration over Liaoning by 67%, mainly from Shandong
      (16%), Hebei (13%), Tianjin (11%) and Korean Peninsula (9%). Identified main city
      receptors in Liaoning are Dandong, Dalian, Chaohu, Yingkou, Liaoyang, Jinfu,
      Shengyang, Panjin, Tieling, Benxi, Anshan and Fushun. At lower layer (120 m)
      where Liaoning local contribution is dominant (58%), regional sources account for
      39% in acid concentration. However, inter-municipal acid exchanges are prominent
      at this layer and many cities in Liaoning are revealed as important sources of
      local acid production. Seasonal acid contribution average within 1.2 km-120 m
      attains 55%, suggesting dominance of vertical pollutant transport from regional
      sources towards lower boundary layer in Liaoning. As direct environmental
      implication, this study provides policy makers with a perspective of regulating
      the regional transboundary environmental impact assessment in China with
      application to acid rain control.

PMID- 29353799
TI  - Seasonal variation of semen parameters correlates with environmental temperature
      and air pollution: A big data analysis over 6 years.
AB  - BACKGROUND: Male fertility is progressively declining in many developed
      countries, but the relationship between male infertility and environmental
      factors is still unclear. OBJECTIVES: To assess the influence of environmental
      temperature and air pollution on semen parameters, using a big-data approach.
      METHODS: A big data analysis of parameters related to 5131 men, living in a
      province of Northern Italy and undergoing semen analyses between January 2010 and
      March 2016 was performed. Ambient temperature was recorded on the day of analysis
      and the 90 days prior to the analysis and the average value of particulate matter
      (PM) and NO2 in the year of the test. All data were acquired by geocoding
      patients residential address. A data warehouse containing 990,904,591 data was
      generated and analysed by multiple regressions. RESULTS: 5573 semen analyses were
      collected. Both maximum and minimum temperatures registered on the day of
      collection were inversely related to total sperm number (p < .001), non
      progressive motility (NPrM) (p < .005) and normal forms (p < .001). Results were
      confirmed considering temperature in the 30 and 60 days before collection, but
      not in the 90 days before collection. Total sperm number was lower in
      summer/autumn (p < .001) and was inversely related with daylight duration (p <
      .001). PM10 and PM2.5 were inversely related to PrM (p < .001 and p < .005) and
      abnormal forms (p < .001). CONCLUSIONS: This is the first evaluation of the
      relationship between male fertility-related parameters and environment using a
      big-data approach. A seasonal change in semen parameters was found, with a
      fluctuation related to both temperature and daylight duration. A negative
      correlation between air pollution and semen quality is suggested. Such seasonal
      and environmental associations should be considered when assessing changes of
      male fertility-related parameters over time.

PMID- 29353800
TI  - Public perception and attitude towards chemical industry park in Dalian, Bohai
      Rim.
AB  - Recent decade has witnessed accelerating expansion of chemical industry and
      increasing conflicts between the local citizens, governmental authorities and
      project developers, especially in some coastal and port cities in China.
      Development and transformation of chemical industrial parks has been adopted as a
      national initiative recently. However, there is a paucity of research examining
      public perspectives on chemical industrial parks and their risks. Aiming to
      understand public perception, attitude, and response and the factors underlying
      the support/acceptance of chemical industry park, this paper investigated 418
      residents neighboring to two chemical industrial parks, Dalian in Bohai Rim
      through face-to-face questionnaire survey. The results showed the knowledge of
      the respondents on the chemical industrial parks development was very limited.
      The respondents had complex perceptions on the environmental impacts, risks
      control, social-economic benefits, and problem awareness. The current levels of
      information disclosure and public participation were very low. The central
      governmental official (44.3%) was the most trustworthy group by the respondents.
      Only 5.5% and 23.2% of the respondents supported the construction of a new CIP
      nearby and far away their homes, whilst 13% thought new CIP project as
      acceptable. The spearman correlation analysis results showed a strong NIMBY
      effect (Not In My Backyard). Factor analysis results demonstrated five latent
      factors: knowledge, benefit, information, trust, and participation. Multiple
      linear regression analysis indicated how socio-demographic differences and five
      latent factors might impact on the support/acceptance of the chemical industrial
      parks. Education level, trust, information, and participation were significant
      predictors of public support/acceptance level. This study contributes to our
      limited knowledge and understanding of public sentiments to the chemical industry
      parks in China.

PMID- 29353801
TI  - TERT regulates telomere-related senescence and apoptosis through DNA damage
      response in male germ cells exposed to BPDE in vitro and to B[a]P in vivo.
AB  - Increasing evidence shows that impaired telomere function is associated with male
      infertility, and various environmental factors are believed to play a pivotal
      role in telomerase deficiency and telomere shortening. Benzo[a]pyrene (B[a]P), a
      ubiquitous pollutant of polycyclic aromatic hydrocarbons (PAHs), can act as a
      reproductive toxicant; however, the adverse effect of B[a]P on telomeres in male
      reproductive cells has never been studied, and the related mechanisms remain
      unclear. In this study, we explored the effects of benzo[a]pyrene-7,8-dihydrodiol
      9,10-epoxide (BPDE), the active metabolite of B[a]P, on telomere dysfunction in
      mouse spermatocyte-derived cells (GC-2) and also the potential role of telomerase
      in BPDE-induced spermatogenic cell damage. The results showed that BPDE induced
      cell viability inhibition, senescence, and apoptosis in GC-2 cells in a dose
      dependent manner. Shortened telomeres, telomere-associated DNA damage, reduced
      telomerase activity, and TERT expression were also observed in BPDE-treated
      cells, accompanied with the activation of DNA damage response pathway
      (ATM/Chk1/p53/p21). Moreover, by establishing the TERT knockdown and re
      expression cell models, we found that TERT regulated telomere length and the
      expression of DNA damage response-related proteins to influence senescence and
      apoptosis in GC-2 cells. These in vitro findings were further confirmed in vivo
      in the testicular cells of rats orally administrated with B[a]P for 7 days. B[a]P
      treatment resulted in histological lesions, apoptosis, and senescence in the
      testes of rats, which were accompanied by shortened telomeres, reduced levels of
      TERT protein, and increased expression of DNA damage response-related proteins.
      In conclusion, it can be concluded that TERT-mediated telomere dysfunction
      contributes to B[a]P- and BPDE-induced senescence and apoptosis through DNA
      damage response in male reproductive cells.

PMID- 29353802
TI  - Effects of carbamazepine and cetirizine under an ocean acidification scenario on
      the biochemical and transcriptome responses of the clam Ruditapes philippinarum.
AB  - Several works evaluated the toxicity of pharmaceutical drugs and climate related
      changes in invertebrates but few explored the combined effects of both stressors,
      namely considering their mode of action (MoA). Carbamazepine (CBZ) and cetirizine
      (CTZ) are pharmaceutical drugs detected in the environment and the toxicity
      derived from the combined effects of these drugs with ocean acidification (OA) is
      poorly explored. Thus, the present study investigated the biochemical parameters
      related to an oxidative stress response and the transcription of genes related to
      the MoA of CBZ (1.0 MUg/L) and CTZ (0.6 MUg/L) in the clam Ruditapes
      philippinarum chronically exposed (28 days) to control (7.8) and low (7.5) pH
      conditions. The results obtained showed that despite the clams accumulated both
      drugs, at low pH the clams exposed to CTZ decreased drug concentration and BCF
      values (CTZ uptake: 2.0 +/- 0.5 ng/g fresh weight; BCF: 3.8 +/- 0.9) in
      comparison with clams exposed to control pH (CTZ uptake: 2.9 +/- 0.3 ng/g fresh
      weight; BCF: 5.5 +/- 0.6). No oxidative stress was induced by the exposure to CBZ
      or CTZ at each pH level, but the transcription of several genes related with the
      MoA (neurotransmission, immunity and biomineralization) was altered by low pH,
      drug exposure and the combination of both stressors. At both pH conditions, CBZ
      increased the transcription of GABA receptor gene (neurotransmission) and CTZ led
      to a decrease of Perlucin gene (biomineralization) transcription. The
      transcription of MyD88 gene (immunity) decreased at low pH (7.5) combined with
      drug exposure (CBZ or CTZ). Thus, it was highlighted that the interaction of drug
      exposure and low pH conditions can change bivalves' sensitivity to drugs or alter
      drugs toxicity.

PMID- 29353803
TI  - Metagenome enrichment approach used for selection of oil-degrading bacteria
      consortia for drill cutting residue bioremediation.
AB  - Drill cuttings leave behind thousands of tons of residues without adequate
      treatment, generating a large environmental liability. Therefore knowledge about
      the microbial community of drilling residue may be useful for developing
      bioremediation strategies. In this work, samples of drilling residue were
      enriched in different culture media in the presence of petroleum, aiming to
      select potentially oil-degrading bacteria and biosurfactant producers. Total DNA
      was extracted directly from the drill cutting samples and from two enriched
      consortia and sequenced using the Ion Torrent platform. Taxonomic analysis
      revealed the predominance of Proteobacteria in the metagenome from the drill
      cuttings, while Firmicutes was enriched in consortia samples. Functional analysis
      using the Biosurfactants and Biodegradation Database (BioSurfDB) revealed a
      similar pattern among the three samples regarding hydrocarbon degradation and
      biosurfactants production pathways. However, some statistical differences were
      observed between samples. Namely, the pathways related to the degradation of
      fatty acids, chloroalkanes, and chloroalkanes were enriched in consortia samples.
      The degradation colorimetric assay using dichlorophenolindophenol as an indicator
      was positive for several hydrocarbon substrates. The consortia were also able to
      produce biosurfactants, with biosynthesis of iturin, lichnysin, and surfactin
      among the more abundant pathways. A microcosms assay followed by gas
      chromatography analysis showed the efficacy of the consortia in degrading
      alkanes, as we observed a reduction of around 66% and 30% for each consortium in
      total alkanes. These data suggest the potential use of these consortia in the
      bioremediation of drilling residue based on autochthonous bioaugmentation.

PMID- 29353804
TI  - Sensitive analysis of steroid estrogens and bisphenol a in small volumes of water
      using isotope-dilution ultra-performance liquid chromatography-tandem mass
      spectrometry.
AB  - An isotope-dilution ultra-performance liquid chromatography-electrospray tandem
      mass spectrometry method combined with dansylation was established to sensitively
      quantify four steroid estrogens (estrone, 17alpha-estradiol, 17beta-estradiol and
      17alpha-ethynylestradiol) and bisphenol A in sewage influent and effluent. A
      simple hexane extraction was performed from a small volume (10 mL), followed by
      dansyl chloride derivatization and purification with a silica cartridge. The
      method effectively reduced the matrix effects in sample extract and permitted the
      selective and sensitive determination of target compounds from complicated
      matrices. The detection limits of the method for steroid estrogens were 0.20-0.90
      ng L-1 in influent and 0.10-0.20 ng L-1 in effluent samples. For bisphenol A, the
      limits detection of the method were 20 and 0.80 for influent and effluent
      samples, respectively. Recoveries of 85%-96% were observed in all matrices. The
      method was applied to analyze residual estrogens and bisphenol A in sewage
      influent and effluent samples from Beijing, China. The concentrations of
      bisphenol A (636-1200 ng L-1) were up to 250 times higher than those of steroid
      estrogens. Estrone was the dominant estrogen in influent and effluent samples,
      while similar concentrations of 17alpha-estradiol and 17beta-estradiol were
      detected in all samples.

PMID- 29353805
TI  - Sources and distribution of microplastics in China's largest inland lake -
      Qinghai Lake.
AB  - Microplastic pollution was studied in China's largest inland lake - Qinghai Lake
      in this work. Microplastics were detected with abundance varies from 0.05 * 105
      to 7.58 * 105 items km-2 in the lake surface water, 0.03 * 105 to 0.31 * 105
      items km-2 in the inflowing rivers, 50 to 1292 items m-2 in the lakeshore
      sediment, and 2 to 15 items per individual in the fish samples, respectively.
      Small microplastics (0.1-0.5 mm) dominated in the lake surface water while large
      microplastics (1-5 mm) are more abundant in the river samples. Microplastics were
      predominantly in sheet and fiber shapes in the lake and river water samples but
      were more diverse in the lakeshore sediment samples. Polymer types of
      microplastics were mainly polyethylene (PE) and polypropylene (PP) as identified
      using Raman Spectroscopy. Spatially, microplastic abundance was the highest in
      the central part of the lake, likely due to the transport of lake current. Based
      on the higher abundance of microplastics near the tourist access points, plastic
      wastes from tourism are considered as an important source of microplastics in
      Qinghai Lake. As an important area for wildlife conservation, better waste
      management practice should be implemented, and waste disposal and recycling
      infrastructures should be improved for the protection of Qinghai Lake.

PMID- 29353806
TI  - Historical atmospheric pollution trends in Southeast Asia inferred from lake
      sediment records.
AB  - Fossil fuel combustion leads to increased levels of air pollution, which
      negatively affects human health as well as the environment. Documented data for
      Southeast Asia (SEA) show a strong increase in fossil fuel consumption since
      1980, but information on coal and oil combustion before 1980 is not widely
      available. Spheroidal carbonaceous particles (SCPs) and heavy metals, such as
      mercury (Hg), are emitted as by-products of fossil fuel combustion and may
      accumulate in sediments following atmospheric fallout. Here we use sediment SCP
      and Hg records from several freshwater lentic ecosystems in SEA (Malaysia,
      Philippines, Singapore) to reconstruct long-term, region-wide variations in
      levels of these two key atmospheric pollution indicators. The age-depth models of
      Philippine sediment cores do not reach back far enough to date first SCP
      presence, but single SCP occurrences are first observed between 1925 and 1950 for
      a Malaysian site. Increasing SCP flux is observed at our sites from 1960 onward,
      although individual sites show minor differences in trends. SCP fluxes show a
      general decline after 2000 at each of our study sites. While the records show
      broadly similar temporal trends across SEA, absolute SCP fluxes differ between
      sites, with a record from Malaysia showing SCP fluxes that are two orders of
      magnitude lower than records from the Philippines. Similar trends in records from
      China and Japan represent the emergence of atmospheric pollution as a broadly
      based inter-region environmental problem during the 20th century. Hg fluxes were
      relatively stable from the second half of the 20th century onward. As catchment
      soils are also contaminated with atmospheric Hg, future soil erosion can be
      expected to lead to enhanced Hg flux into surface waters.

PMID- 29353807
TI  - Multivariate calibration of energy-dispersive X-ray diffraction data for
      predicting the composition of pharmaceutical tablets in packaging.
AB  - A system using energy-dispersive X-ray diffraction (EDXRD) has been developed and
      tested using multivariate calibration for the quantitative analysis of tablet
      form mixtures of common pharmaceutical ingredients. A principal advantage of
      EDXRD over the more traditional and common angular dispersive X-ray diffraction
      technique (ADXRD) is the potential of EDXRD to analyse tablets within their
      packaging, due to the higher energy X-rays used. In the experiment, a series of
      caffeine, paracetamol and microcrystalline cellulose mixtures were prepared and
      pressed into tablets. EDXRD profiles were recorded on each sample and a principal
      component analysis (PCA) was carried out in both unpackaged and packaged
      scenarios. In both cases the first two principal components explained >98% of the
      between-sample variance. The PCA projected the sample profiles into two
      dimensional principal component space in close accordance to their ternary
      mixture design, demonstrating the discriminating potential of the EDXRD system. A
      partial least squares regression (PLSR) model was built with the samples and was
      validated using leave-one-out cross-validation. Low prediction errors of between
      2% and 4% for both unpackaged and packaged tablets were obtained for all three
      chemical compounds. The prediction capability through packaging demonstrates a
      truly non-destructive method for quantifying tablet composition and demonstrates
      good potential for EDXRD to be applied in the field of counterfeit medicine
      screening and pharmaceutical quality control.

PMID- 29353808
TI  - Determination of polymeric impurities in asunaprevir drug substance and product
      using size exclusion effect of reversed-phase columns.
AB  - This paper describes the development of a simple reversed-phase HPLC method that
      can quantitate trace amounts of a polymeric degradants (BMT-041910) in
      asunaprevir drug substance and formulated drug product with quantitation limits
      of ~0.05% w/w. The method has overcome several challenges of polymer quantitation
      such as band broadening, peak coeluting and low sensitivity. The hydrophobic
      function group (BOC) of BMT-041910 is removed to increase its aqueous solubility
      by a simple sample treatment procedure (des-BOC). The des-BOC polymer (BMT
      052076) is excluded from stationary phase pores and eluted as a single peak
      before solvent front, and then its peak area response can be used to determine
      BMT-041910 amount. The HPLC conditions were optimized using a 250 * 4.6 mm Waters
      XSelect CSH column maintained at 30  degrees C with a mobile phase of water
      acetonitrile-trifluoroacetic acid (20:80:0.1 v/v/v). The feasibility of other
      HPLC approaches including size exclusion chromatography and normal phase
      chromatography were also investigated and found to be less suitable for this
      particular application. Validation data for this method in terms of precision,
      linearity, accuracy and sensitivity are also presented.

PMID- 29353809
TI  - Determining particle size and water content by near-infrared spectroscopy in the
      granulation of naproxen sodium.
AB  - Near-infrared spectroscopy is frequently used by the pharmaceutical industry to
      monitor and optimize several production processes. In combination with
      chemometrics, a mathematical-statistical technique, the following advantages of
      near-infrared spectroscopy can be applied: It is a fast, non-destructive, non
      invasive, and economical analytical method. One of the most advanced and popular
      chemometric technique is the partial least square algorithm with its best
      applicability in routine and its results. The required reference analytic enables
      the analysis of various parameters of interest, for example, moisture content,
      particle size, and many others. Parameters like the correlation coefficient, root
      mean square error of prediction, root mean square error of calibration, and root
      mean square error of validation have been used for evaluating the applicability
      and robustness of these analytical methods developed. This study deals with
      investigating a Naproxen Sodium granulation process using near-infrared
      spectroscopy and the development of water content and particle-size methods. For
      the water content method, one should consider a maximum water content of about
      21% in the granulation process, which must be confirmed by the loss on drying.
      Further influences to be considered are the constantly changing product
      temperature, rising to about 54  degrees C, the creation of hydrated states of
      Naproxen Sodium when using a maximum of about 21% water content, and the large
      quantity of about 87% Naproxen Sodium in the formulation. It was considered to
      use a combination of these influences in developing the near-infrared
      spectroscopy method for the water content of Naproxen Sodium granules. The "Root
      Mean Square Error" was 0.25% for calibration dataset and 0.30% for the validation
      dataset, which was obtained after different stages of optimization by
      multiplicative scatter correction and the first derivative. Using laser
      diffraction, the granules have been analyzed for particle sizes and obtaining the
      summary sieve sizes of >63 MUm and >100 MUm. The following influences should be
      considered for application in routine production: constant changes in water
      content up to 21% and a product temperature up to 54  degrees C. The different
      stages of optimization result in a "Root Mean Square Error" of 2.54% for the
      calibration data set and 3.53% for the validation set by using the Kubelka-Munk
      conversion and first derivative for the near-infrared spectroscopy method for a
      particle size >63 MUm. For the near-infrared spectroscopy method using a particle
      size >100 MUm, the "Root Mean Square Error" was 3.47% for the calibration data
      set and 4.51% for the validation set, while using the same pre-treatments. - The
      robustness and suitability of this methodology has already been demonstrated by
      its recent successful implementation in a routine granulate production process.

PMID- 29353810
TI  - Development and validation of a solid phase extraction sample cleanup procedure
      for the recovery of trace levels of nitro-organic explosives in soil.
AB  - An improved cleanup method has been developed for the recovery of trace levels of
      12 nitro-organic explosives in soil, which is important not only for the forensic
      community, but also has environmental implications. A wide variety of explosives
      or explosive-related compounds were evaluated, including nitramines, nitrate
      esters, nitroaromatics, and a nitroalkane. Fortified soil samples were extracted
      with acetone, processed via solid phase extraction (SPE), and then analyzed by
      gas chromatography with electron capture detection. The following three SPE
      sorbents in cartridge format were compared: EmporeTM SDB-XC, Oasis(r) HLB, and
      Bond Elut NEXUS cartridges. The NEXUS cartridges provided the best overall
      recoveries for the 12 explosives in potting soil (average 48%) and the fastest
      processing times (<30min). It also rejected matrix components from spent motor
      oil on potting soil. The SPE method was validated by assessing limit of detection
      (LOD), processed sample stability, and interferences. All 12 compounds were
      detectable at 0.02MUg explosive/gram of soil or lower in the three matrices
      tested (potting soil, sand, and loam) over three days. Seven explosives were
      stable up to seven days at 2MUg/g and three were stable at 0.2MUg/g, both in
      processed loam, which was the most challenging matrix. In the interference study,
      five interferences above the determined LOD for soil were detected in matrices
      collected across the United States and in purchased all-purpose sand, potting
      soil, and loam. This represented a 3.2% false positive rate for the 13 matrices
      processed by the screening method for interferences. The reported SPE cleanup
      method provides a fast and simple extraction process for separating organic
      explosives from matrix components, facilitating sample throughput and reducing
      instrument maintenance. In addition, a comparison study of the validated SPE
      method versus conventional syringe filtration was completed and highlighted the
      benefits of sample cleanup for removing matrix interferences, while also
      providing lower supply cost, order of magnitude lower LODs for most explosives,
      higher percent recoveries for complex matrices, and fewer instrument maintenance
      issues.

PMID- 29353811
TI  - Statin wars: have we been misled about the evidence? A narrative review.
AB  - Statins are the most widely prescribed, cholesterol-lowering drugs in the world.
      Despite the expiration of their patents, revenue for statins is expected to rise,
      with total sales on track to reach an estimated US$1 trillion by 2020. A bitter
      dispute has erupted among doctors over suggestions that statins should be
      prescribed to millions of healthy people at low risk of heart disease. There are
      concerns that the benefits have been exaggerated and the risks have been
      underplayed. Also, the raw data on the efficacy and safety of statins are being
      kept secret and have not been subjected to scrutiny by other scientists. This
      lack of transparency has led to an erosion of public confidence. Doctors and
      patients are being misled about the true benefits and harms of statins, and it is
      now a matter of urgency that the raw data from the clinical trials are released.

PMID- 29353812
TI  - A tale of two metals: contrasting criticalities in the pnictides and hole-doped
      cuprates.
AB  - The iron-based high temperature superconductors share a number of similarities
      with their copper-based counterparts, such as reduced dimensionality, proximity
      to states of competing order, and a critical role for 3d electron orbitals. Their
      respective temperature-doping phase diagrams also contain certain commonalities
      that have led to claims that the metallic and superconducting (SC) properties of
      both families are governed by their proximity to a quantum critical point (QCP)
      located inside the SC dome. In this review, we critically examine these claims
      and highlight significant differences in the bulk physical properties of both
      systems. While there is now a large body of evidence supporting the presence of a
      (magnetic) QCP in the iron pnictides, the situation in the cuprates is much less
      apparent, at least for the end point of the pseudogap phase. We argue that the
      opening of the normal state pseudogap in cuprates, so often tied to a putative
      QCP, arises from a momentum-dependent breakdown of quasiparticle coherence that
      sets in at much higher doping levels but which is driven by the proximity to the
      Mott insulating state at half filling. Finally, we present a new scenario for the
      cuprates in which this loss of quasiparticle integrity and its evolution with
      momentum, temperature and doping plays a key role in shaping the resultant phase
      diagram.

PMID- 29353813
TI  - Pharmacological approach to increase the retention of radiation induced gamma
      H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry.
AB  - In a scenario of accidental mass radiation exposure, transportation and analyzing
      samples may take its time resulting in loss of biomarker information over this
      period. The present study aims to use phosphatases inhibitors for longer
      retention of foci signals to adopt gamma-H2AX as a biodosimetric biomarker for
      the management of early triage. Peripheral blood lymphocytes isolated from
      healthy individuals irradiated in vitro with X-rays, and gamma-H2AX analysed
      using fluorescent microscopy and flow cytometric methods. Further, the effect of
      protein phosphatase 2A inhibitors like Calyculin A, Fostriecin and Okadiac acid
      on the retention of foci were studied. The fluorescent microscopy to be more
      sensitive method when compared to flow cytometry. Calyculin A showed significant
      retention of foci signals at 6h with 1.5 fold increased retention of foci
      signals, this may prove beneficial in early triage management, because of a
      better dose approximation.

PMID- 29353814
TI  - A review of the quantum Hall effects in MgZnO/ZnO heterostructures.
AB  - This review visits recent experimental efforts on high mobility two-dimensional
      electron systems (2DES) hosted at the Mg x Zn[Formula: see text]O/ZnO
      heterointerface. We begin with the growth of these samples, and highlight the key
      characteristics of ozone-assisted molecular beam epitaxy required for their
      production. The transport characteristics of these structures are found to rival
      that of traditional semiconductor material systems, as signified by the high
      electron mobility ([Formula: see text] cm2 Vs-1) and rich quantum Hall features.
      Owing to a large effective mass and small dielectric constant, interaction
      effects are an order of magnitude stronger in comparison with the well studied
      GaAs-based 2DES. The strong correlation physics results in robust Fermi-liquid
      renormalization of the effective mass and spin susceptibility of carriers, which
      in turn dictates the parameter space for the quantum Hall effect. Finally, we
      explore the quantum Hall effect with a particular emphasis on the spin degree of
      freedom of carriers, and how their large spin splitting allows control of the
      ground states encountered at ultra-low temperatures within the fractional quantum
      Hall regime. We discuss in detail the physics of even-denominator fractional
      quantum Hall states, whose observation and underlying character remain elusive
      and exotic.

PMID- 29353815
TI  - The challenge of spin-orbit-tuned ground states in iridates: a key issues review.
AB  - Effects of spin-orbit interactions in condensed matter are an important and
      rapidly evolving topic. Strong competition between spin-orbit, on-site Coulomb
      and crystalline electric field interactions in iridates drives exotic quantum
      states that are unique to this group of materials. In particular, the 'J eff  = 
      1/2' Mott state served as an early signal that the combined effect of strong spin
      orbit and Coulomb interactions in iridates has unique, intriguing consequences.
      In this Key Issues Review, we survey some current experimental studies of
      iridates. In essence, these materials tend to defy conventional wisdom: absence
      of conventional correlations between magnetic and insulating states, avoidance of
      metallization at high pressures, 'S-shaped' I-V characteristic, emergence of an
      odd-parity hidden order, etc. It is particularly intriguing that there exist
      conspicuous discrepancies between current experimental results and theoretical
      proposals that address superconducting, topological and quantum spin liquid
      phases. This class of materials, in which the lattice degrees of freedom play a
      critical role seldom seen in other materials, evidently presents some profound
      intellectual challenges that call for more investigations both experimentally and
      theoretically. Physical properties unique to these materials may help unlock a
      world of possibilities for functional materials and devices. We emphasize that,
      given the rapidly developing nature of this field, this Key Issues Review is by
      no means an exhaustive report of the current state of experimental studies of
      iridates.

PMID- 29353816
TI  - Human parvovirus B19-associated hematopathy in HIV disease: need for
      clinicopathological revisit.

PMID- 29353818
TI  - Safety of axitinib and sorafenib monotherapy for patients with renal cell
      carcinoma: a meta-analysis.
AB  - We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma
      (RCC) patients and compare toxicity of these two vascular endothelial growth
      factor receptor inhibitors. Databases of PubMed and Embase were searched. We
      included phase II and III prospective trials, as well as retrospective studies,
      in which patients diagnosed with RCC were treated with axitinib or sorafenib
      monotherapy at a starting dose of 5 mg and 400 mg twice daily, respectively. The
      overall incidence of high grade hypertension, fatigue, gastrointestinal toxicity
      and hand-foot syndrome, along with their 95% confidence intervals (CI), were
      calculated using fixed- or random- effects model according to heterogeneity test
      results. A total of 26 trials, including 4790 patients, were included in our meta
      analysis. Among them, 6 arms were related to axitinib and 22 were associated with
      sorafenib. The incidences of hypertension (24.9% vs. 7.9%), fatigue (8.2% vs.
      6.6%), and gastrointestinal toxicity (17.6% vs. 11.3%) were higher in patients
      receiving axitinib versus those receiving sorafenib, while the incidence of hand
      foot syndrome was lower in patients receiving axitinib versus those receiving
      sorafenib (9.5% vs. 13.3%). In conclusion, axitinib showed noticeably higher
      risks of toxicity versus sorafenib. Close monitoring and effective measures for
      adverse events are recommended during therapy.

PMID- 29353817
TI  - Transforming growth factor-beta signaling in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a complex, multiorgan autoimmune disease of unknown
      etiology. Manifestation of the disease results from an interaction of three key
      pathologic features including irregularities of the antigen-specific immune
      system and the non-specific immune system, resulting in autoantibody production,
      vascular endothelial activation of small blood vessels, and tissue fibrosis as a
      result of fibroblast dysfunction. Given the heterogeneity of clinical
      presentation of the disease, a lack of universal models has impeded adequate
      testing of potential therapies for SSc. Regardless, recent research has
      elucidated the roles of various ubiquitous molecular mechanisms that contribute
      to the clinical manifestation of the disease. Transforming growth factor beta
      (TGF-beta) has been identified as a regulator of pathological fibrogenesis in
      SSc. Various processes, including cell growth, apoptosis, cell differentiation,
      and extracellular matrix synthesis are regulated by TGF-beta, a type of cytokine
      secreted by macrophages and many other cell types. Understanding the essential
      role TGF-beta pathways play in the pathology of systemic sclerosis could provide
      a potential outlet for treatment and a better understanding of this severe
      disease.

PMID- 29353819
TI  - Interference with the C-terminal structure of MARF1 causes defective oocyte
      meiotic division and female infertility in mice.
AB  - Meiosis-arrest female 1 (MARF1) is a recently identified key oogenic regulator
      essential for the maintenance of female fertility and genome integrity in mice.
      However, the detailed functions and the underlying mechanisms of MARF1 remain
      elusive. Here, in an attempt to create a mouse model expressing fluorescent
      protein-tagged MARF1 to facilitate further exploration of the roles of MARF1 in
      oocytes, we produced a Marf1-eGFP knockin (KI) mouse line in which the C-terminal
      structure and function of MARF1 were interfered by its fusing eGFP peptide. Using
      these Marf1-eGFP-KI mice, we revealed, unexpectedly, the functions of MARF1 in
      the control of oocyte meiotic division. We found that the Marf1-eGFP-KI females
      ovulated mature oocytes with severe meiotic and developmental defects, and thus
      were infertile. Moreover, meiotic reinitiation was delayed while meiotic
      completion was accelerated in the KI-oocytes, which was coincident with the
      increased incidence of oocyte aneuploidy. Therefore, MARF1 is indispensable for
      maintaining the fidelity of homolog segregation during oocyte maturation, and
      this function relies on its C-terminal domains.

PMID- 29353820
TI  - Cervical spine fractures in osteopetrosis: a case report and review of the
      literature.
AB  - While management of appendicular fractures has been well described in the setting
      of osteopetrosis, there is limited information on managing fractures of the axial
      spine. Here we present an osteopetrotic patient with multiple traumatic multiple,
      comminuted, unstable cervical spinal fractures managed with non-operative
      stabilization, and provide a review of the pathophysiology, genetic
      characteristics, and special considerations that must be explored when
      determining operative versus non-operative management of spinal injury in
      osteopetrosis. A PubMed query was performed for English articles in the
      literature published up to June 2016, and used the following search terms alone
      and in combination: "osteopetrosis", "spine", "fractures", "osteoclasts", and
      "operative management". Within four months after initial injury, treatment with
      halo vest allowed for adequate healing. The patient was asymptomatic with
      cervical spine dynamic radiographs confirming stability at four months. On four
      year follow up examination, the patient remained without neck pain, and CT scan
      demonstrated partially sclerotic fracture lines with appropriate anatomical
      alignment. In conclusion, external halo stabilization may be an effective option
      for treatment of multiple unstable acute traumatic cervical spine fractures in
      patients with osteopetrosis. Given the challenge of surgical stabilization in
      osteopetrosis, further research is necessary to elucidate the optimal form of
      treatment in this select patient population.

PMID- 29353821
TI  - Efficacy and safety of metyrosine in pheochromocytoma/paraganglioma: a multi
      center trial in Japan.
AB  - To assess the efficacy, safety, and pharmacokinetics of metyrosine (an inhibitor
      of catecholamine synthesis) in patients with pheochromocytoma/paraganglioma
      (PPGL), we conducted a prospective, multi-center, open-label study at 11 sites in
      Japan. We recruited PPGL patients aged >=12 years requiring preoperative or
      chronic treatment, receiving alpha-blocker treatment, having baseline urinary
      metanephrine (uMN) or normetanephrine (uNMN) levels >=3 times the upper limit of
      normal values, and having symptoms associated with excess catecholamine.
      Metyrosine treatment was started at 500 mg/day and modified according to dose
      adjustment criteria up to 4,000 mg/day. The main outcome measure was the
      proportion of patients who achieved at least 50% reduction in uMN or uNMN levels
      from baseline. Sixteen patients (11 males/5 females) aged 12-86 years
      participated. After 12 weeks of treatment and at the last evaluation of efficacy,
      the primary endpoint was achieved in 31.3% of all patients, including 66.7% of
      those under preoperative treatment and 23.1% of those under chronic treatment.
      Sedation, anemia, and death were reported in 1 patient each as serious adverse
      drug reactions during the 24-week treatment. Metyrosine was shown to be tolerated
      and to relieve symptoms by reducing excess catecholamine in PPGL patients under
      both preoperative and chronic treatment.

PMID- 29353822
TI  - Quantitative angiographic anatomy of the renal arteries and adjacent aorta in the
      swine for preclinical studies of intravascular catheterization devices.
AB  - Swine are the most common animal model in preclinical studies of cardiovascular
      devices. Because of the recent trend for development of new devices for
      percutaneous catheterization, especially for the renal arteries (RAs), we
      examined the quantitative anatomical dimensions of the RAs and adjacent aorta in
      swine. Angiographic images were analyzed in 66 female Yorkshire/Landrace
      crossbred swine. The diameter of both the right and left main RA was 5.4 +/- 0.6
      mm. The length of the right main RA was significantly longer than that of the
      left (29.8 +/- 7.5 mm vs. 20.6 +/- 5.4 mm, respectively; P<0.001). The diameter
      of both the right and left branch RA with diameters >=3 mm (the target vessel
      diameter of recently developed devices) was 3.8 +/- 0.5 mm. The right branch RA
      was significantly longer than that of the left (18.9 +/- 7.8 mm vs. 16.4 +/- 7.4
      mm, respectively; P<0.05). The branching angle of the right RA from the aorta was
      significantly smaller than that of the left (91 +/- 12 degrees  vs. 103 +/- 15
      degrees , respectively; P<0.001). The diameters of the suprarenal and infrarenal
      aorta were 10.6 +/- 1.1 mm and 9.7 +/- 0.9 mm, respectively. In conclusion,
      because of their similar dimensions to human, swine are an appropriate animal
      model for assessing the safety of, and determining optimal design of, catheter
      devices for RAs in simulated clinical use. However, there were species
      differences in the branching angle and adjacent aorta diameter, suggesting that
      swine models alone are inadequate to assess the delivery performance of catheter
      devices for RAs.

PMID- 29353823
TI  - Increased Expression of Y-Box-Binding Protein-1 in Hind-Limb Muscles During
      Regeneration from Ischemic Injury in Mice.
AB  - Critical limb ischemia (CLI) is the most severe complication of peripheral
      arterial disease (PAD). Understanding the molecular mechanisms underlying tissue
      repair after CLI is necessary for preventing PAD progression. Y-box binding
      protein-1 (YB-1) regulates the expression of many genes in response to
      environmental stresses. We aimed to determine whether YB-1 is involved in
      ischemic muscle regeneration. A mouse ischemic hind-limb model was generated;
      namely, the femoral, saphenous, and popliteal arteries in the left hind limb were
      ligated. The right hind limb, with skin incisions alone, served as control. Hind
      limbs (n = 3-5 for each time point) were examined on day 0 (before the operation)
      and on postoperative days 1, 2, 7, 10, and 14, and the biceps femoris, adductor,
      rectus femoris, and gracilis muscles were subjected to histopathological and
      immunohistochemical analyses. In ischemic limbs, myogenesis, triggered by an
      increase in myotubes, began on day 7; thereafter, regenerated muscles gradually
      increased in volume. RT-PCR analysis showed that YB-1 mRNA levels were increased
      in the limbs after ischemic injury, peaked on day 2, and subsequently decreased.
      On day 7, expression levels of MyoD and alpha-smooth muscle actin (alphaSMA)
      mRNAs were significantly higher in ischemic muscles than in control muscles.
      Immunohistochemical analysis revealed increased YB-1 immunoreactivity in
      myoblasts and myotubes on day 7, which was decreased by day 14. The
      immunoreactive alphaSMA and smooth muscle myosin heavy chain were transiently
      increased in myotubes. This is the first report showing the increased expression
      of YB-1 during muscle regeneration after ischemic injury.

PMID- 29353824
TI  - Alcohol Consumption and Breast Cancer Risk According to Hormone Receptor Status
      in Japanese Women: A Case-Control Study.
AB  - Alcohol consumption is a risk factor for breast cancer in Western countries, but
      few studies have evaluated the risk for Japanese women, who have a relatively low
      alcohol intake. This case-control study investigated the association of alcohol
      consumption with breast cancer risk according to estrogen-receptor and
      progesterone-receptor (ER/PgR) status in Japanese women. From female patients
      aged 30 years and over admitted to a single hospital in Japan between 1997 and
      2011, 1,256 breast cancer cases (669 ER+/PgR+, 162 ER+/PgR-, 21 ER-/PgR+, 305 ER
      /PgR-, and 99 missing) and 2,933 controls were selected. Alcohol-related measures
      were assessed using a self-administered questionnaire. Unconditional logistic
      regression analysis was performed. Alcohol-related measures were not associated
      with breast cancer risk among the women overall. Moreover, no association was
      observed between ever drinking and the risk of a concordant receptor subtype
      (ER+/PgR+ or ER-/PgR-). Conversely, ever drinking was inversely associated with
      the risk of discordant subtype (ER+/PgR-, odds ratio (OR) = 0.63, 95% confidence
      interval (CI): 0.41-0.95; ER-/PgR+, OR = 0.44, 95% CI: 0.14-1.42). For ER+/PgR-,
      an inverse association with the amount of alcohol consumed per day was observed
      (P for trend = 0.04), and this inverse association was limited to premenopausal
      women. Alcohol consumption may have differential effects on concordant and
      discordant receptor subtypes of breast cancer. In view of the low frequency of
      discordant subtype in Japanese women and their relatively low alcohol intake, our
      findings may provide a clue for elucidating the etiology of breast cancer rather
      than for preventing discordant subtype.

PMID- 29353825
TI  - Treatment Patterns and Lipid Profile in Patients with Familial
      Hypercholesterolemia in Japan.
AB  - AIM: To evaluate the epidemiology and real-world treatment patterns associated
      with lipid-modifying therapies (LMTs) among groups of Japanese patients with
      familial hypercholesterolemia (FH). METHODS: A retrospective observational study
      was conducted using an electronic hospital-based administrative claims database
      and electronic medical records. Patients with existing diagnosis of FH (FH-D) and
      patients with suspected FH (FH-S) defined by low-density lipoprotein cholesterol
      (LDL-C) >=190 mg/dL were included, and medical records of hospitals across Japan
      were analyzed to assess the diagnostic status, management of LDL-C levels, and
      treatment patterns. RESULTS: Among the 3,495 patients who met the inclusion
      criteria, 193 patients were FH-D and 3,339 patients were FH-S. Among them, 83.5%
      had not achieved the LDL-C of <100 mg/dL recommended for patients with FH at the
      index date. Mean LDL-C levels for all patients and for FH-D and FH-S patients
      were 145.8 mg/dL, 119.2 mg/dL, and 147.6 mg/dL, respectively. 44.5% of the
      patients were not currently treated with LMTs. High-intensity statins were used
      only in 19.2% and 2.3% of the FH-D and FH-S patients, respectively. Furthermore,
      among the FH-D and FH-S statin-treated patients, 61 (69.3%) and 1,059 (89.7%)
      remained on monotherapy even when their LDL-C was >=100 mg/dL. CONCLUSIONS:
      Treatment and management of LDL-C in Japanese FH patients remain suboptimal. The
      results suggest that FH is underdiagnosed in real-world, routine clinical
      practice in Japan. There is an urgent need to improve the diagnostic rate of FH
      and to provide the appropriate therapy to achieve the recommended LDL-C levels of
      <100 mg/dL or a more than 50% reduction for patients with FH in Japan.

PMID- 29353826
TI  - The Association between Glomerular Filtration Rate Estimated on Admission and
      Acute Stroke Outcome: The Shiga Stroke Registry.
AB  - AIM: Although renal dysfunction has been identified as a novel risk factor
      affecting stroke prognosis, few have analyzed the association within large-scale
      population-based setting, using wide-range estimated glomerular filtration rate
      (eGFR) category. We aimed to determine the association of admission eGFR with
      acute stroke outcomes using data from a registry established in Shiga Prefecture,
      Japan. METHODS: Following exclusion of patients younger than 18 years, with
      missing serum creatinine data, and with onset more than 7 days prior to
      admission, 2,813 acute stroke patients registered in the Shiga Stroke Registry
      year 2011 were included in the final analysis. The Japanese Society of Nephrology
      equation was used to estimate GFR. Multivariable logistic regression was
      performed to analyze the association of eGFR with all-cause in-hospital death
      (modified Rankin Scale [mRS] 6), and at-discharge death/disability (mRS 2-6).
      Separate analyses were conducted within stroke subtypes. RESULTS: Compared to
      eGFR 60-89 mL/min/1.73 m2, adjusted odds ratios (ORs) and 95% confidence interval
      [95% CI] for in-hospital death (in the order of eGFR <45, 45-59, and >=90
      mL/min/1.73 m2) were 1.54 [1.04-2.27], 1.07 [0.72-1.58], and 1.04 [0.67-1.59].
      Likewise, adjusted ORs [95% CI] for at-discharge death/disability were 1.54 [1.02
      2.32], 0.97 [0.73-1.31], and 1.48 [1.06-2.05]. Similar pattern was further
      evident in the eGFR <45 mL/min/1.73 m2 group for both outcomes within acute
      ischemic stroke patients. CONCLUSIONS: Our study has ascertained that in acute
      stroke, particularly ischemic stroke, low eGFR was significantly associated with
      in-hospital death and at-discharge death/disability. Additionally, high eGFR was
      found to be associated with at-discharge death/disability.

PMID- 29353828
TI  - [What Is Necessary for Radiation Technology Studies for Big Data and AI Era?]

PMID- 29353829
TI  - [Dispatch Reports on the Chinese Society of Imaging Technology (CSIT)].

PMID- 29353830
TI  - [Academic Exchange Agreement between JSRT and TWSRT].

PMID- 29353827
TI  - Oral Fat Tolerance Test for Sitosterolemia and Familial Hypercholesterolemia: A
      Study Protocol.
AB  - AIM: Sitosterolemia is an extremely rare, autosomal recessive disease
      characterized by high plasma cholesterols and plant sterols because of increased
      absorption of dietary cholesterols and sterols from the intestine, and decreased
      excretion from biliary tract. Previous study indicated that sitosterolemic
      patients might be vulnerable to post-prandial hyperlipidemia, including high
      remnant-like lipoprotein particles (RLP) level. Here we evaluate whether a
      loading dietary fat increases a post-prandial RLP cholesterol level in
      sitosterolemic patients compared to heterozygous familial hypercholesterolemic
      patients (FH). METHODS: We recruit total of 20 patients: 5 patients with
      homozygous sitosterolemia, 5 patients with heterozygous sitosterolemia, and 10
      patients with heterozygous FH as controls from May 2015 to March 2018 at Kanazawa
      University Hospital, Japan. All patients receive Oral Fat Tolerance Test (OFTT)
      cream (50 g/body surface area square meter, orally only once, and the cream
      includes 34% of fat, 74 mg of cholesterol, and rich in palmitic and oleic acids.
      The primary endpoint is the change of a RLP cholesterol level after OFTT cream
      loading between sitosterolemia and FH. We measure them at baseline, and 2, 4, and
      6 hours after the oral fat loading. RESULTS: This is the first study to evaluate
      whether sitosterolemia patients have a higher post-prandial RLP cholesterol level
      compared to heterozygous FH patients. CONCLUSION: The result may become an
      additional evidence to restrict dietary cholesterols for sitosterolemia. This
      study is registered at University Hospital Medical Information Network (UMIN)
      Clinical Trials Registry (UMIN ID: UMIN000020330).

PMID- 29353831
TI  - [Recent Topics of Small and Medium Enterprise and Information Technology Industry
      Promotion Committee (SME?IT Committee)].

PMID- 29353832
TI  - [The Measurement Precision and Accuracy of T1 Mapping Using Polarity Corrected
      (PC) TI Prep Tool].
AB  - The aim of this study was to evaluate the measurement precision and accuracy of
      T1 mapping using a polarity corrected (PC) TI prep tool, which was based on fast
      field echo (FFE) and obtained one data point with one inversion recovery (IR)
      pulse. A phantom was used consisting of eight materials with different Gd
      concentrations. T1 mappings were measured by changing the trigger interval and
      the inversion time (TI) interval. The T1 mapping measurement precision using the
      PC TI prep tool increased as the trigger interval was made longer. The
      measurement precision didn't depend on the interval of TI. On the other hand,
      when the trigger intervals are more than 1000 ms, the measurement accuracy was
      less than approximately 8%. By setting the optimal end of TI, the T1 mapping
      using a PC TI prep tool could measure the T1 value precisely and accurately.

PMID- 29353833
TI  - [Evaluation of Organ Dose Estimation from Indices of CT Dose Using Dose Index
      Registry].
AB  - Direct measurement of each patient organ dose from computed tomography (CT) is
      not possible. Most methods to estimate patient organ dose is using Monte Carlo
      simulation with dedicated software. However, dedicated software is too expensive
      for small scale hospitals. Not every hospital can estimate organ dose with
      dedicated software. The purpose of this study was to evaluate the simple method
      of organ dose estimation using some common indices of CT dose. The Monte Carlo
      simulation software Radimetrics (Bayer) was used for calculating organ dose and
      analysis relationship between indices of CT dose and organ dose. Multidetector CT
      scanners were compared with those from two manufactures (LightSpeed VCT, GE
      Healthcare; SOMATOM Definition Flash, Siemens Healthcare). Using stored patient
      data from Radimetrics, the relationships between indices of CT dose and organ
      dose were indicated as each formula for estimating organ dose. The accuracy of
      estimation method of organ dose was compared with the results of Monte Carlo
      simulation using the Bland-Altman plots. In the results, SSDE was the feasible
      index for estimation organ dose in almost organs because it reflected each
      patient size. The differences of organ dose between estimation and simulation
      were within 23%. In conclusion, our estimation method of organ dose using indices
      of CT dose is convenient for clinical with accuracy.

PMID- 29353834
TI  - [Evaluation of Efficiencies on the Gadoxetic Acid-enhanced MRI for Preoperative
      Assessment of Liver Metastases from Colorectal Carcinoma].
AB  - THE AIMS OF OUR STUDY WERE: 1) to evaluate efficiencies of gadoxetic acid
      enhanced magnetic resonance imaging (Gd-EOB-MRI) for preoperative assessment of
      liver metastases from colorectal carcinoma, and 2) to compare them with other
      diagnostic imaging modalities. The subjects of the analysis were outpatients with
      advanced colorectal cancer who are at risk of developing liver metastases
      (initial setting: pre-test probability=20%). At initial setting, we performed a
      decision analysis to calculate numbers of true positive (TP), false negative
      (FN), false positive (FP) and true negative (TN) test results per 1000 patients
      of Gd-EOB-MRI and other imaging modalities (conventional contrast agent-enhanced
      MRI, contrast-enhanced CT and 18F-FDG PET/CT). From the result of decision
      analysis, we calculated the cost of detection per one patient with liver
      metastases (detection cost). Also, we calculated positive predictive value (PPV)
      and negative predictive value (NPV). Moreover, these values were defined as
      efficiencies in this study. In the initial setting, number of TP, FN, FP TN
      results and detection cost of Gd-EOB-MRI were 197, 3, 40, 760, and 224,032.8
      Japanese Yen, respectively. Also, PPV and NPV were 83.1% and 99.7%, respectively.
      In comparison with other imaging modalities, efficiencies of Gd-EOB-MRI were
      superior to them, except detection cost. We consider that the efficiencies of Gd
      EOB-MRI, which we had assessed are easy to understand and useful when they are
      used for explanation to patients.

PMID- 29353835
TI  - [Improvement of CT Imaging with a Metal Artifact Reduction Technique for
      Radiation Treatment Planning-Fundamental Study of Structure Delineation and Dose
      Calculation].
AB  - In radiotherapy planning, CT images are widely used to delineate the gross tumor
      volume (GTV) and the organs at risks (OARs), which allows for the calculation of
      the dose distribution to each structure. The delineated contours of the GTV and
      OARs may become inaccurate, and subsequently result in the inaccurate derivation
      of the dose distribution, if there are metal artifacts present in the CT image.
      The metal artifact reduction technique, single energy metal artifact reduction
      (SEMAR), installed on the CT system (Aquilion ONETM Vision Edition, Toshiba
      Medical Systems Corporation) could potentially reduce metal artifacts. Therefore,
      we investigated whether SEMAR can improve the accuracy of delineation, and
      subsequently the dosimetric accuracy, in the treatment planning process. Using an
      acrylonitrile-butadiene-styrene resin phantom (RT-3000-New, R-Tech. Inc, Tokyo,
      Japan), titanium bars were inserted on both the left and right sides, and four
      types of electron density inserts (rods) were separately inserted in the middle.
      The electron densities of the rods were 0.90, 0.96, 1.07, and 1.09. After CT
      images were acquired, SEMAR-ON (when applying the SEMAR correction) images were
      generated. On both SEMAR-ON and SEMAR-OFF (when not applying the SEMAR
      correction) images, the rod contours were delineated automatically, using a CT
      value threshold. This threshold was selected so that the area of the
      automatically delineated contour was 615.4 mm2. The difference in the contour
      area of SEMAR-ON, SEMAR-OFF, and no metal artifact images were compared using the
      dice coefficient. When SEMAR was used, the dice coefficient improved by 57.4%.
      Therefore, SEMAR was considered to be useful in improving the accuracy of GTV and
      OAR delineation.

PMID- 29353836
TI  - [Optimal Conditions for 3D Non-contrast T1-weighted Magnetic Resonance Imaging
      Segmented Turbo Fast Low-angle Shot for Tissue Characterization of Coronary
      Plaques].
AB  - In three-dimensional (3D) T1-weighted magnetic resonance imaging used for tissue
      characterization of coronary plaques, the contrast for electrocardiographic
      synchronization may vary according to the R-R interval (RR). The coronary artery
      plaque image shows suppression of the fluid compartment signal for the coronary
      artery luminal blood as well as the fat signal in the region of interest; in
      addition, it is necessary to ensure that the value of the plaque-to-muscle signal
      intensity ratio (PMR) does not change according to the difference in RR. In the
      current study, the phantom review and clinical data suggested that the PMR
      changes that occur due to the differences in RR can be minimized by adjusting the
      inversion time (TI) in the range of the required black blood effect. Moreover,
      the signal-to-noise ratio (SNR), which varies according to the difference between
      the RR and the TI, was determined to identify the maximum value flip angle (FA)
      value that would lead to improvement in the SNR. Thus, signal suppression of the
      PMR, SNR, and the fluid compartment of the coronary artery luminal blood can be
      controlled using different RRs with the relational expressions for calculating
      optimal TI and FA.

PMID- 29353838
TI  - [7. DRL for Interventional Radiology Examination].

PMID- 29353837
TI  - [Effect of Tube Voltage on Contrast Enhancement and Contrast Medium Dose in
      Abdominal Contrast-enhanced Computed Tomography].
AB  - The purpose of this study was to investigate the effect of tube voltage on
      relationship between a patient's body weight and contrast enhancement in
      abdominal contrast-enhanced computed tomography (CT). Five phantoms with
      diameters ranging from 19.2 to 30.6 cm, including syringes filled with iodine
      solution diluted to different concentrations, were used to compare the effects at
      tube voltages of 80, 100, and 120 kVp. Furthermore, for clinical study, 300
      patients who underwent abdominal contrast-enhanced CT examinations were enrolled
      and enhancements of aorta and hepatic parenchyma in arterial phase and
      equilibrium phase were compared at 80, 100, and 120 kVp using a contrast medium
      administration proportional to the body weight. The contrast enhancement was
      decreased with increase in phantom size because of the beam-hardening effect, and
      however, the decrease was less at low tube voltages of 80 and 100 kVp (lowest at
      80 kVp), demonstrating the beam-hardening effect was reduced at low tube
      voltages. The enhancements of aorta and hepatic parenchyma indicated tended to
      increase in patients with a heavy body weight, and this trend was stronger at 80
      and 100 kVp (80 kVp>100 kVp). Therefore, it was indicated that the problem of
      excessive contrast enhancement in patients with a high body weight was prominent
      at low tube voltages because the beam-hardening effect in patients with a heavy
      body weight was weaken by low tube voltages.

PMID- 29353839
TI  - [3. Researches of Drug Delivery System and Theranostics Using Pre-clinical MRI].

PMID- 29353840
TI  - [7. Radiation Therapy for Prostate Cancer].

PMID- 29353842
TI  - [1. Flow of Outpatient Care Using Image Diagnosis Including Sonography for
      Gynecologic Tumor].

PMID- 29353843
TI  - [About the Radiological Technology].

PMID- 29353844
TI  - [Progress in research of NASH].

PMID- 29353845
TI  - [Recent progress in the treatment of chronic hepatitis B].

PMID- 29353846
TI  - [A case of adult gastric volvulus treated using upper gastrointestinal series].
AB  - Here, we report a case of adult gastric volvulus that was treated using an upper
      gastrointestinal series and provide a review of relevant reports. A 55-year-old
      woman presented with upper abdominal pain. Abdominal computed tomography revealed
      mesenteroaxial gastric volvulus. We performed an upper gastrointestinal series
      after the placement of a nasogastric tube. We successfully performed detorsion by
      repositioning. There was no recurrence of gastric volvulus after the detorsion.
      However, considering the risk of recurrence, we also performed laparoscopic
      gastropexy. The postoperative course was uneventful, and she was discharged from
      the hospital on postoperative day 3. No recurrence of symptoms has been observed
      to date.

PMID- 29353847
TI  - [Diagnosis and treatment of six patients with Crohn's disease complicated by
      recto-perineal-urethral fistula].
AB  - Recto-perineal-urethral fistula caused by Crohn's disease is a rare, for which
      fundamental treatment has not been established yet. We analyzed the clinical
      characteristics, diagnosis, treatment, and prognosis of six male patients with
      anorectal lesions caused by Crohn's disease. Three patients were treated with
      abdominoperineal resection and the other three with rectal excision without
      anastomosis. Excluding one case, which presented worsening immediately after
      surgery, symptoms of urethral fistula improved without urethral stenosis,
      dysuria, or sexual dysfunction. Recto-perineal-urethral fistula is currently
      treated with various treatment modalities, including colostomy and drug therapy.
      Although the evaluation of these modalities is required, abdominoperineal
      resection or rectal excision without anastomosis may be a valuable treatment
      option because these approaches improve the urethral fistula while sparing the
      urethra without any significant complications.

PMID- 29353849
TI  - [Identify cases that require hepatitis B treatment -Understanding the hepatitis B
      virus marker helps diagnosis and treatment of hepatitis B patients].

PMID- 29353850
TI  - [Current issues and management of long-term nucleos(t)ide analogues treatment for
      chronic hepatitis B].

PMID- 29353848
TI  - [A case of intracholecystic papillary neoplasm of the gallbladder (ICPN) examined
      using contrast-enhanced endoscopic ultrasonography].
AB  - A 78-year-old woman was found to have gallbladder wall thickening on
      ultrasonography during a routine health check-up and was referred to our clinic.
      On contrast-enhanced endoscopic ultrasonography, a papillary lesion measuring
      14mm was detected in the fundus, which showed a heterogeneous enhancement at the
      early phase. She underwent cholecystectomy and gallbladder bed resection.
      Histological examination revealed that the tumor consisted of mucinous atypical
      cells, regularly arranged in a high-papillary architecture with delicate
      fibrovascular cores, which led to the diagnosis of intracholecystic papillary
      neoplasm of the gallbladder.

PMID- 29353851
TI  - [Recent status of HBV reactivation in Japan and the strategy to prevent severe
      hepatitis].

PMID- 29353852
TI  - [Latest information about drug development of hepatitis B and future prospect].

PMID- 29353853
TI  - ?

PMID- 29353854
TI  - [A case of duodenal neuroendocrine carcinoma composed of small- and large-cell
      types].
AB  - A 78-year-old man underwent a detailed examination by upper gastrointestinal
      endoscopy for the complaint of epigastric pain. The examination revealed a
      hemicircumferential type 2 tumor in the descending duodenum. A subsequent biopsy
      led to a diagnosis of neuroendocrine carcinoma. Subtotal stomach-preserving
      pancreaticoduodenectomy was performed. The lesion was composed of small- and
      large-cell neuroendocrine carcinomas. The large-cell type component was positive
      for both caudal homeobox protein 2 and the cluster of differentiation 138,
      whereas the small-cell type component was negative for both. Our report may
      provide valuable information regarding the pathogenesis of neuroendocrine
      carcinoma.

PMID- 29353855
TI  - [Sigmoid colon cancer with intussusception prolapsing through the anus treated by
      elective laparoscopic radical surgery].
AB  - An 86-year-old man was brought in ambulance to our hospital because of sudden
      hematochezia and abdominal pain during defecation. Intestinal prolapse
      approximately 80mm from the anus and a type 1 tumor 50mm in size on the mucosal
      surface were detected. The intestinal prolapse was manually repositioned, and the
      reduction of the intussusception was confirmed by computed tomography (CT).
      Following colonoscopy and abdominal-enhanced CT, a sigmoid colon cancer without
      distant metastases was detected. Elective laparoscopic radical surgery was
      performed. The present study described a rare case of sigmoid colon cancer with
      an intussusception prolapsing through the anus and highlighted the treatment
      strategy by reviewing 48 previous cases. The treatment strategy employed was as
      follows:first, manual repositioning of the intestinal prolapse was attempted;and
      second, the presence of intussusception was confirmed by CT. In cases when
      repositioning of the intussusception was not possible, even with the use of an
      endoscope or contrast enema, emergency surgery was required.

PMID- 29353856
TI  - [Pneumatosis cystoides intestinalis (PCI) with sigmoid volvulus:a case
      potentially associated with lymphatic vessels].
AB  - An 80-year-old woman was brought to our hospital in an ambulance because of signs
      of peritoneal irritation. Computed tomography revealed volvulus, sigmoid colon
      dilation, and free air and pneumatosis within the colonic and bowel wall. An
      emergency laparotomy was performed after the diagnosis of colonic perforation
      associated with volvulus or pneumatosis. Numerous gas-filled cysts, up to 10mm in
      diameter, were located in the resected bowel wall. The cells at the inner lining
      of the cysts tested positive for D2-40 immunoreactivity, seemingly originating
      from the lymphatic vessels. In many cysts, KP-1 positive small mononuclear cells
      and/or foreign-body-type giant cells adhered to the D2-40 positive cells were
      observed. Fibrosis and lymphoplasmacytic infiltration was observed around the
      cysts. Contrary to the influential mechanical cause theory, in the present case,
      pneumatosis may have preceded volvulus, occurring as an idiopathic disease.
      Therefore, the lymphatic vessels were hypothesized to be associated with the
      pathogenesis of PCI.

PMID- 29353857
TI  - New hematological key for bovine leukemia virus-infected Japanese Black cattle.
AB  - The European Community's (EC) Key, which is also called Bendixen's Key, is a well
      established bovine leukemia virus (BLV) diagnostic method that classifies cattle
      according to the absolute lymphocyte count and age. The EC Key was originally
      designed for dairy cattle and is not necessarily suitable for Japanese Black (JB)
      beef cattle. This study revealed the lymphocyte counts in the BLV-free and 
      infected JB cattle were significantly lower than those in the Holstein cattle.
      Therefore, applying the EC Key to JB cattle could result in a large number of
      undetected BLV-infected cattle. Our proposed hematological key, which was
      designed for JB cattle, improves the detection of BLV-infected cattle by
      approximately 20%. We believe that this study could help promote BLV control.

PMID- 29353858
TI  - Seasonal changes in circulating gonadal steroid levels and physiological evidence
      for the presence of intrinsic circannual reproductive cycles in captive finless
      porpoises Neophocaena asiaeorientalis from the western Inland Sea, Japan.
AB  - We monitored annual fluctuations of gonadal steroid levels in three sexually
      mature captive finless porpoises (Neophocaena asiaeorientalis; two males and one
      female) from two different facilities over 56-91 months. Two animals (one male
      and one female) were held in an indoor tank with a sunroof (facility A) and the
      other male was held in an indoor tank without a sunroof (facility B). Water
      temperatures in both facilities reflected seasonal changes during the study
      period with a minor difference in the fluctuation pattern. Testosterone levels of
      the male in facility A were higher from spring to summer every year and exhibited
      a 12-month cycle. The female showed estrus cycles in 1-month intervals from
      summer to winter, excluding 2 anestrus years. In contrast, the period of higher
      testosterone levels of the male in facility B gradually initiated earlier over
      the years under a constant photoperiod (11.5L:12.5D) and exhibited a 9-month
      cycle during the first 52 months. After changing the light conditions to a
      natural photoperiod, its testosterone levels were high from early spring to
      summer for 3 consecutive years and exhibited a 12-month cycle. Our results showed
      that under a constant artificial photoperiod, the male in facility B failed to
      recognize the seasonal changes of a natural external environment, resulting in a
      9-month, free-running hormone cycle.

PMID- 29353859
TI  - Towards a wearable sensor system for continuous occupational cold stress
      assessment.
AB  - This study investigated the usefulness of continuous sensor data for improving
      occupational cold stress assessment. Eleven volunteer male subjects completed a
      90-120-min protocol in cold environments, consisting of rest, moderate and hard
      work. Biomedical data were measured using a smart jacket with integrated
      temperature, humidity and activity sensors, in addition to a custom-made sensor
      belt worn around the chest. Other relevant sensor data were measured using
      commercially available sensors. The study aimed to improve decision support for
      workers in cold climates, by taking advantage of the information provided by data
      from the rapidly growing market of wearable sensors. Important findings were that
      the subjective thermal sensation did not correspond to the measured absolute skin
      temperature and that large differences were observed in both metabolic energy
      production and skin temperatures under identical exposure conditions.
      Temperature, humidity, activity and heart rate were found to be relevant
      parameters for cold stress assessment, and the locations of the sensors in the
      prototype jacket were adequate. The study reveals the need for cold stress
      assessment and indicates that a generalised approached is not sufficient to
      assess the stress on an individual level.

PMID- 29353860
TI  - Association of Hyperthyroidism and Thyroid Autoantibodies with Moyamoya Disease
      and Its Stroke Event: A Population-based Case-control Study and Meta-analysis.
AB  - The aim of this study was to investigate the specific thyroid condition and
      thyroid autoantibodies in adult moyamoya disease (MMD) according to clinical
      presentation (ischemia vs. hemorrhage stroke). In addition, a meta-analysis was
      performed to reveal the association between adult MMD and elevated thyroid
      function, or autoantibodies. Prospectively collected data on 169 consecutive
      patients with MMD at a single institution were analyzed. Community-based controls
      matched for age and sex were selected for comparison. Penalized multinomial
      logistic regression analysis was used for factors affecting stroke. For meta
      analysis, heterogeneity was evaluated by using the I2 test. If I2 < 50%, a fixed
      effect model was used. Fifty-four cases (32.0%) presented with ischemic stroke
      and 37 cases (21.9%) with hemorrhage stroke. Hyperthyroidism had a marginally
      increased risk of MMD with ischemic stroke with reference value of MMD without
      stroke [odds ratio (OR), 2.53; P = 0.055]. Anti-thyroperoxidase antibody (TPOAb)
      increased the risk of MMD presenting with ischemic stroke significantly (OR,
      2.99; P = 0.020). A meta-analysis revealed that adult MMD was significantly
      associated with elevated autoantibodies (OR, 7.663; P = 0.002) and
      hyperthyroidism (OR, 10.936; P < 0.001). Elevated TPOAb and hyperthyroidism may
      play important roles in adult MMD with ischemic stroke. Studies focusing on
      targeted hyperthyroidism and thyroid autoantibodies are necessary in treating
      adult MMD patients in the future.

PMID- 29353861
TI  - Neuroprotection Mediated by Upregulation of Endothelial Nitric Oxide Synthase in
      Rho-Associated, Coiled-Coil-Containing Kinase 2 Deficient Mice.
AB  - BACKGROUND: Rho-associated kinases (ROCK1 and ROCK2) are important regulators of
      the actin cytoskeleton and endothelial nitric oxide synthase (eNOS). Because the
      phosphorylation of eukaryotic elongation factor-1A1 (eEF1A1) by ROCK2 is critical
      for eNOS expression, we hypothesized that this molecular pathway may play a
      critical role in neuroprotection following focal cerebral ischemia.Methods and
      Results:Adult male wild-type (WT) and mutant ROCK2 and eNOS-/-mice were subjected
      to middle cerebral artery occlusion (MCAO), and cerebral infarct size,
      neurological deficit and absolute cerebral blood flow were measured. In addition,
      aortic endothelium-dependent response to acetylcholine, NG-nitro-L-arginine
      methyl ester (L-NAME) and sodium nitroprusside were assessed ex vivo. Endothelial
      cells from mouse brain or heart were used to measure eNOS and eEF1A activity, as
      well as NO production and eNOS mRNA half-life. In global hemizygous ROCK2+/-and
      endothelial-specific EC-ROCK2-/-mice, eNOS mRNA stability and eNOS expression
      were increased, which correlated with enhanced endothelium-dependent relaxation
      and neuroprotection following focal cerebral ischemia. Indeed, when ROCK2+/-mice
      were place on an eNOS-/-background, the neuroprotective effects observed in
      ROCK2+/-mice were abolished. CONCLUSIONS: These findings indicate that the
      phosphorylation of eEF1A1 by ROCK2 is physiologically important for eNOS
      expression and NO-mediated neuroprotection, and suggest that targeting
      endothelial ROCK2 and eEF1A may have therapeutic benefits in ischemic stroke and
      cardiovascular disease.

PMID- 29353862
TI  - Clinical Predictors of Right Ventricular Myocardial Fibrosis in Patients With
      Repaired Tetralogy of Fallot.
AB  - BACKGROUND: This study aimed to identify the clinical predictors of the degree of
      right ventricular (RV) myocardial fibrosis in patients with repaired tetralogy of
      Fallot (TOF) with special focus on the RV pressure load.Methods and Results:From
      April 2004 to March 2017, 30 patients with repaired TOF underwent pulmonary valve
      replacement and concomitant RV myocardial biopsy. The stroke volume ratio (RV
      stroke volume/left ventricular stroke volume), RV end-diastolic volume index, and
      right-to-left ventricular systolic pressure ratio were evaluated with respect to
      their prognostic value for the degree of RV myocardial fibrosis. Significant
      positive linear correlations were detected between the stroke volume ratio and
      the degree of RV myocardial fibrosis (P=0.003, r=0.52). Patients with a right-to
      left ventricular systolic pressure ratio >0.45 showed a significantly greater
      degree of RV myocardial fibrosis under an equivalent stroke volume ratio.
      CONCLUSIONS: Under conditions of RV volume overload, a right-to-left ventricular
      systolic pressure ratio >0.45 was a predisposing factor for progression of RV
      myocardial fibrosis in patients with repaired TOF.

PMID- 29353863
TI  - Epizootic of sarcoptic mange in raccoon dogs (Nyctereutes procyonoides) in
      relation to population density.
AB  - To examine outbreaks of mange in raccoon dogs (Nyctereutes procyonoides) with
      respect to population density, we analyzed camera trap videos, and isolated mites
      from raccoon dog carcasses. In a camera trapping survey, we categorized the skin
      condition of raccoon dogs, and used a number of independent videos to calculate
      the relative abundance index (RAI). The RAI of raccoon dogs with alopecia
      increased following an increase in the RAI of those without alopecia. Among 27
      raccoon dog carcasses, 12 showed mange-compatible skin lesions. Sarcoptes scabiei
      was isolated from 11 of these raccoon dogs, indicating that sarcoptic mange was
      endemic in our study area. Therefore, a high relative population density may be a
      factor underlying epizootics of sarcoptic mange in raccoon dogs.

PMID- 29353864
TI  - Development of Probiotic Formulation for the Treatment of Iron Deficiency Anemia.
AB  - Probiotics are increasingly more present both as functional foods, and in
      pharmaceutical preparations with multiple levels of action that contribute to
      human health. Probiotics realize their positive effects with a proper dose, and
      by maintaining a declared number of probiotics cells by the expiration date.
      Important precondition for developing a probiotic product is the right choice of
      clinically proven probiotic strain, the choice of other active components, as
      well as, the optimization of the quantity of active component of probiotic per
      product dose. This scientific paper describes the optimization of the number of
      probiotics cells in the formulation of dietary supplement that contains probiotic
      culture Lactobacillus plantarum 299v, iron and vitamin C. Variations of the
      quantity of active component were analyzed in development batches of the
      encapsulated probiotic product categorized as dietary supplement with the
      following ingredients: probiotic culture, sucrosomal form of iron and vitamin C.
      Optimal quantity of active component L. plantarum of 50 mg, was selected. The
      purpose of this scientific paper is to select the optimal formulation of
      probiotic culture in a dietary supplement that contains iron and vitamin C, and
      to also determine its expiration date by the analysis of the number of viable
      probiotic cells.

PMID- 29353865
TI  - An 18-Year Follow-up Survey of Dioxin Levels in Human Milk in Japan.
AB  - BACKGROUND: Globally, few published studies have tracked the temporal trend of
      dioxin levels in the human body since 2000. This study describes the annual trend
      of dioxin levels in human breast milk in Japanese mothers from 1998 through 2015.
      METHODS: An observational study was conducted from 1998 through 2015.
      Participants were 1,194 healthy mothers following their first delivery who were
      recruited annually in Japan. Breast milk samples obtained from participants were
      analyzed using gas chromatography and mass spectrometry for dioxins, including
      polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      and coplanar polychlorinated biphenyls (PCBs). RESULTS: Mean age was 29.5 years,
      and 53% of participants were 20-25 years old. A declining trend in total dioxin
      levels was found, from a peak of 20.8 pg toxic equivalence (TEQ)/g fat in 1998 to
      7.2 pg TEQ/g fat in 2014. Data from the last 5 years of the study indicated a
      plateau at minimal levels. In contrast, an increasing trend was found in the mean
      age of participants during the last 5 years. Although significantly higher dioxin
      levels were observed in samples from older participants, an upward trend in
      dioxin levels was not observed, indicating that dietary and environmental
      exposure to dioxins had greatly diminished in recent years. CONCLUSIONS: Dioxin
      levels in human breast milk may be approaching a minimum in recent years in
      Japan. The findings may contribute to global reference levels for environmental
      pollution of dioxins, which remains a problem for many developing countries.

PMID- 29353866
TI  - Weight Status, Physical Activity, and Depression in Korean Older Adults.
AB  - BACKGROUND: This study aimed to explore the associations between weight status,
      physical activity, and depression in Korean older adults. METHODS: We used the
      baseline data drawn from the 2008 baseline survey utilized in the Living Profiles
      of Older People Survey, comprised of 15,146 community-dwelling older people
      (42.6% men and 57.4% women) aged 60 years and older residing in the Republic of
      Korea. After excluding respondents with missing data on height, weight, and
      physical activity (PA), data on 10,197 samples (43.3% men and 56.7% women) were
      analyzed in this study. RESULTS: Underweight and completely inactive individuals
      had poorer sociodemographic and health behavioral characteristics and increased
      risks of late-life depression compared with normal weight and sufficiently active
      individuals, respectively. In terms of the aerobic PA guidelines, completely
      inactive individuals had a significantly higher risk of late-life depression
      (odds ratio 1.730; 95% confidence interval, 1.412-2.120) compared with
      sufficiently active individuals, even after adjustments for age, education,
      household income, night sleeping, living status, marital status, smoking, number
      of comorbidities, nutritional status, self-reported health status, and cognitive
      performance as covariates. In addition, those who did not meet the PA guidelines
      and were underweight or overweight/obese were more likely to have late-life
      depression compared to those who were active and normal weight. CONCLUSIONS: The
      current findings of the study suggest that modifiable, lifestyle risk factors,
      such as physical inactivity, underweight, and overweight/obesity, are positively
      associated with late-life depression in Korean older adults.

PMID- 29353868
TI  - Telomeres and subtelomeres: new insights into the chromatin structures and
      functions of chromosome ends.

PMID- 29353869
TI  - Lipofection of siRNA into bovine 8-16-cell stage embryos using zona removal and
      the well-of-the-well culture system.
AB  - Bovine preimplantation embryos exhibit dramatic biological changes between before
      and after the 8-16-cell stage. Here we report a simple lipofection method to
      transfect siRNA into bovine 8-16-cell stage embryos using zona removal and the
      well-of-the-well (WOW) culture system. Bovine one-cell embryos produced in vitro
      were freed from the zona pellucida and cultured up to the 8-16-cell stage in WOW
      dishes. The 8-16-cell embryos were lipofected with siRNA and the transfection
      efficiency was assessed at 48 h of transfection. Lipofection with a red
      fluorescent non-targeting siRNA revealed the importance of zona removal for
      transfection of siRNA into embryos. Using this method, we knocked down the
      methionine adenosyltransferase 2A (MAT2A) gene, achieving a significant reduction
      in MAT2A expression (P < 0.05) concomitant with the marked inhibition of
      blastocyst development. Our proposed method, tentatively named 'Octo
      lipofection', may be useful to analyze gene functions in bovine preimplantation
      embryos without expensive equipment and skill-intensive techniques.

PMID- 29353867
TI  - Factors controlling sperm migration through the oviduct revealed by gene-modified
      mouse models.
AB  - Mammalian fertilization is comprised of many steps including sperm survival in
      the uterus, sperm migration in the female reproductive tract, physiological and
      morphological changes to the spermatozoa, and sperm-egg interaction in the
      oviduct. In vitro studies have revealed essential factors for these fertilization
      steps for over half a century. However, the molecular mechanism of fertilization
      has recently been revised by the emergence of genetically modified animals. Here,
      we focus on essential factors for sperm fertilizing ability and describe recent
      advances in our knowledge of the mechanisms of mammalian fertilization,
      especially of sperm migration from the uterus into the oviduct.

PMID- 29353870
TI  - Efficiency of stem cell based therapy in the treatment of diabetic foot ulcer: a
      meta-analysis.
AB  - Diabetic foot ulcer is a chronic, refractory, frequent complication in diabetic
      patient. Its treatment often requires multidisciplinary joint efforts, diverse
      strategies have been adopted to address this annoying issue, including stem cell
      based therapy/acellular dermal matrix/negative pressure wound therapy etc.
      However, consensus has not been reached. To assess the current evidence regarding
      the efficiency and potential advantages of stem cell-based therapy compared with
      conventional standard treatment and/or placebo in the treatment of diabetic foot
      ulcer. A comprehensive search in PubMed, EmBase, Cochrane Central and Web of
      Science databases was conducted during December 2016 and a systematic review and
      meta-analysis of all relevant studies were performed. A total of 7 studies that
      involved 224 diabetic foot patients, classified as Wagner grades 1-5, were
      analyzed. The pooled results confirmed the benefits of using the stem cell
      treatment. Partial and/or complete healing were significantly higher in the stem
      cell group compared with the control group (77.4% vs. 31.9%; RR: 2.22; 95% CI,
      1.65-2.98). Subgroup analysis on ABI and TCP02 also confirmed the results. The
      present meta-analysis indicates that stem cell-based therapy can enhance the
      healing of diabetic foot ulcers and is associated with lesser pain, lower
      amputation rate and improved prognosis compared with normal treatment. Well
      designed randomized controlled trials are required in the future in order to
      confirm and update these findings.

PMID- 29353871
TI  - Minimally Invasive Cardiac Surgery in China: Multi-Center Experience.
AB  - BACKGROUND To the best of our knowledge, there is no nationwide data available on
      the development of minimally invasive cardiac surgery (MICS) in China. The
      purpose of this study was to report the results of MICS in 6 experienced centers
      in China. MATERIAL AND METHODS From September 2014 to July 2016, 1241 patients
      with cardiac conditions who underwent MICS procedures were randomly enrolled in 6
      centers in China, and those patients were randomly selected for inclusion in this
      study. The MICS procedures were defined as any cardiac surgery performed through
      a less invasive incision, rather than a complete median sternotomy, mainly
      including mini-incision surgery (400, 32.2%), video-assisted approach (265,
      21.3%), completely thoracoscopic approach without robotic assistance (504,
      40.6%), and robotic procedure (55, 4.4%). RESULTS The 5 most common in-hospital
      complications were respiratory failure (28, 2.3%), reoperation for all reasons
      (19, 1.5%), renal failure (11, 0.9%), heart failure (9, 0.7%), and stroke (6,
      0.5%). The multivariate logistic regression analysis results showed that
      cardiopulmonary bypass (CPB) time (P=0.033), aortic cross-clamp time (P=0.003),
      cannulation approach (P=0.010), and left ventricular ejection fraction (LVEF)
      (P=0.003) at baseline were all significant risk factors of any in-hospital
      complication of MICS procedures. CONCLUSIONS From our experience, minimally
      invasive cardiac approaches are safe and reproducible, with acceptable CPB and
      aortic cross-clamp time duration and low mortality.

PMID- 29353872
TI  - Atypical Presentation of a Rare Disease: Eosinophilic Cholangitis Posing as a
      Cancer.
AB  - BACKGROUND A variety of benign etiologies of biliary stricture may initially be
      mistaken for hilar cholangiocarcinoma. Consequently, many patients undergo
      surgery for a benign disease that could have been treated medically. Eosinophilic
      cholangitis (EC) is an uncommon, benign, self-limiting disease that should be
      considered when approaching a case of obstructive jaundice since it causes
      biliary stricture formation. Transmural eosinophilic infiltration of the biliary
      tree is characteristic of EC. It may initially be indistinguishable from hilar
      cholangiocarcinoma. CASE REPORT We present a rare case of an 84-year-old male who
      was referred to our hospital for abdominal mass investigation with the
      provisional diagnosis of cholangiocarcinoma. During the workup, the index of
      suspicion for malignancy remained high as the typical laboratory and radiological
      findings for benign causes of biliary stricture were not present. Hence, the
      patient underwent left hepatectomy with caudate lobe resection and received a
      retrograde diagnosis of EC. CONCLUSIONS This case demonstrates that EC could
      present in the elderly with cardinal signs of cancer and absence of the typical
      findings of EC which was not previously reported. Since only 70% of patients
      present with peripheral eosinophilia, we stress on the importance of implementing
      diagnostic criteria for EC in the setting where peripheral eosinophilia is
      absent. Furthermore, this disorder has been reported to respond well to steroid
      therapy, hence, diagnostic criteria for EC would provide another treatment option
      for elderly and/or those who are not fit for surgery.

PMID- 29353873
TI  - Functional genomics: A drop in an ocean of gene variants.

PMID- 29353874
TI  - Technique: SNP-CLINGing onto your post in the genome.

PMID- 29353875
TI  - Cost-effectiveness analyses of genetic and genomic diagnostic tests.
AB  - Developments in next-generation sequencing technologies have driven the clinical
      application of diagnostic tests that interrogate the whole genome, which offer
      the chance to diagnose rare inherited diseases or inform the targeting of
      therapies. New genomic diagnostic tests compete with traditional approaches to
      diagnosis, including the genetic testing of single genes and other clinical
      strategies, for finite health-care budgets. In this context, decision analytic
      model-based cost-effectiveness analysis is a useful method to help evaluate the
      costs versus consequences of introducing new health-care interventions. This
      Perspective presents key methodological, technical, practical and organizational
      challenges that must be considered by decision-makers responsible for the
      allocation of health-care resources to obtain robust and timely information about
      the relative cost-effectiveness of the increasing numbers of emerging genomic
      tests.

PMID- 29353876
TI  - Dandelions, tulips and orchids: evidence for the existence of low-sensitive,
      medium-sensitive and high-sensitive individuals.
AB  - According to empirical studies and recent theories, people differ substantially
      in their reactivity or sensitivity to environmental influences with some being
      generally more affected than others. More sensitive individuals have been
      described as orchids and less-sensitive ones as dandelions. Applying a data
      driven approach, we explored the existence of sensitivity groups in a sample of
      906 adults who completed the highly sensitive person (HSP) scale. According to
      factor analyses, the HSP scale reflects a bifactor model with a general
      sensitivity factor. In contrast to prevailing theories, latent class analyses
      consistently suggested the existence of three rather than two groups. While we
      were able to identify a highly sensitive (orchids, 31%) and a low-sensitive group
      (dandelions, 29%), we also detected a third group (40%) characterised by medium
      sensitivity, which we refer to as tulips in keeping with the flower metaphor.
      Preliminary cut-off scores for all three groups are provided. In order to
      characterise the different sensitivity groups, we investigated group differences
      regarding the Big Five personality traits, as well as experimentally assessed
      emotional reactivity in an additional independent sample. According to these
      follow-up analyses, the three groups differed in neuroticism, extraversion and
      emotional reactivity to positive mood induction with orchids scoring
      significantly higher in neuroticism and emotional reactivity and lower in
      extraversion than the other two groups (dandelions also differed significantly
      from tulips). Findings suggest that environmental sensitivity is a continuous and
      normally distributed trait but that people fall into three distinct sensitive
      groups along a sensitivity continuum.

PMID- 29353877
TI  - Gene variants and educational attainment in cannabis use: mediating role of DNA
      methylation.
AB  - Genetic and sociodemographic risk factors potentially associated with cannabis
      use (CU) were investigated in 40 cannabis users and 96 control subjects. DNA
      methylation analyses were also performed to explore the possibility of epigenetic
      changes related to CU. We conducted a candidate gene association study that
      included variants involved in the dopaminergic (ANKK1, NCAM1 genes) and
      endocannabinoid (CNR1, CNR2 gene) pathways. Sociodemographic data included
      gender, marital status, level of education, and body mass index. We used MeDIP
      qPCR to test whether variations in DNA methylation might be associated with CU.
      We found a significant association between SNP rs1049353 of CNR1 gene (p = 0.01)
      and CU. Differences were also observed related to rs2501431 of CNR2 gene (p =
      0.058). A higher education level appears to decrease the risk of CU.
      Interestingly, females were less likely to use cannabis than males. There was a
      significantly higher level of DNA methylation in cannabis users compared to
      controls in two of the genes tested: hypermethylation at exon 8 of DRD2 gene (p =
      0.034) and at the CpG-rich region in the NCAM1 gene (p = 0.0004). Both genetic
      variants and educational attainment were also related to CU. The higher rate of
      DNA methylation, evidenced among cannabis users, may be either a marker of CU or
      a consequence of long-term exposure to cannabis. The identified genetic variants
      and the differentially methylated regions may represent biomarkers and/or
      potential targets for designs of pharmacological therapeutic agents. Our
      observations also suggest that educational programs may be useful strategies for
      CU prevention.

PMID- 29353878
TI  - Psychosocial characteristics as potential predictors of suicide in adults: an
      overview of the evidence with new results from prospective cohort studies.
AB  - In this narrative overview of the evidence linking psychosocial factors with
      future suicide risk, we collected results from published reports of prospective
      studies with verified suicide events (mortality or, less commonly,
      hospitalisation) alongside analyses of new data. There is abundant evidence
      indicating that low socioeconomic position, irrespective of the economic status
      of the country in question, is associated with an increased risk of suicide,
      including the suggestion that the recent global economic recession has been
      responsible for an increase in suicide deaths and, by proxy, attempts. Social
      isolation, low scores on tests of intelligence, serious mental illness (both
      particularly strongly), chronic psychological distress, and lower physical
      stature (a marker of childhood exposures) were also consistently related to
      elevated suicide rates. Although there is some circumstantial evidence for
      psychosocial stress, personality disposition, and early-life characteristics such
      as bullying being risk indices for suicide, the general paucity of studies means
      it is not currently possible to draw clear conclusions about their role. Most
      suicide intervention strategies have traditionally not explored the modification
      of psychosocial factors, partly because evidence linking psychosocial factors
      with suicide risk is, as shown herein, largely in its infancy, or, where is does
      exist, for instance for intelligence and personality disposition, the
      characteristics in question do not appear to be easily malleable.

PMID- 29353881
TI  - Hypertension with diabetes mellitus complications.
AB  - Chronic diabetic complications are classified as microvascular or macrovascular
      and contribute to mortality and loss of quality of life. Hyperglycemia plays a
      critical role in the pathogenesis of microvascular complications, such as
      diabetic retinopathy, incipient nephropathy, and neuropathy, while
      atherosclerosis contributes to the pathogenesis of macrovascular complications.
      Diabetes mellitus and hypertension are frequently present together. Among many
      microvascular diabetic complications, hypertension plays a predominant role in
      the progression of diabetic nephropathy by glomerular hyperfiltration.
      Hypertension also induces atherosclerosis in diabetes. Thus, hypertension is a
      high-risk factor for both microvascular and macrovascular chronic diabetic
      complications. In this review, we summarize the current knowledge on the
      pathophysiological mechanisms of microvascular and macrovascular chronic diabetic
      complications with particular emphasis on the contribution of hypertension. We
      also briefly discuss various options available for the treatment of each diabetic
      complication.

PMID- 29353879
TI  - Shifting priorities: highly conserved behavioral and brain network adaptations to
      chronic stress across species.
AB  - Parallel clinical and preclinical research have begun to illuminate the
      biological basis of stress-related disorders, including major depression, but
      translational bridges informing discrete mechanistic targets for intervention are
      missing. To address this critical need, we used structural MRI in a mouse model
      and in a large human sample to examine stress effects on brain structure that may
      be conserved across species. Specifically, we focused on a previously unexplored
      approach, whole-brain structural covariance, as it reflects synchronized changes
      in neuroanatomy, potentially due to mutual trophic influences or shared
      plasticity across regions. Using the unpredictable chronic mild stress (UCMS)
      paradigm in mouse we first demonstrate that UCMS-induced elevated behavioral
      emotionality correlates with increased size of the amygdala and other
      corticolimbic regions. We further identify focal increases in the amygdala's
      'hubness' (degree and strength) set against the background of a global stress
      related loss of network clustering and modularity. These macroscopic changes are
      supported on the molecular level by increased postsynaptic density-95 protein in
      the amygdala, consistent with stress-induced plastic changes and synaptic
      strengthening. Finally, we provide clinical evidence that strikingly similar
      structural network reorganization patterns exist in young adults reporting high
      childhood trauma and increased mood symptoms. Collectively, we provide initial
      translational evidence for a conserved stress-related increase in amygdala
      centered structural synchrony, as measured by enhanced structural covariance,
      which is paralleled by a decrease in global structural synchrony. This putative
      trade-off reflected in increased amygdala-centered plastic changes at the expense
      of global structural dedifferentiation may represent a mechanistic pathway for
      depression and related psychopathology.

PMID- 29353880
TI  - Differential effect of disease-associated ST8SIA2 haplotype on cerebral white
      matter diffusion properties in schizophrenia and healthy controls.
AB  - Brain white matter abnormalities are evident in individuals with schizophrenia,
      and also their first-degree relatives, suggesting that some alterations may
      relate to underlying genetic risk. The ST8 alpha-N-acetyl-neuraminide alpha-2,8
      sialyltransferase 2 (ST8SIA2) gene, which encodes the alpha-2,8-sialyltransferase
      8B enzyme that aids neuronal migration and synaptic plasticity, was previously
      implicated as a schizophrenia susceptibility gene. This study examined the extent
      to which specific haplotypes in ST8SIA2 influence white matter microstructure
      using diffusion-weighted imaging of individuals with schizophrenia (n = 281) and
      healthy controls (n = 172), recruited across five Australian sites. Interactions
      between diagnostic status and the number of haplotype copies (0 or >=1) were
      tested across all white matter voxels with cluster-based statistics. Fractional
      anisotropy (FA) in the right parietal lobe was found to show a significant
      interaction between diagnosis and ST8SIA2 protective haplotype (p < 0.05, family
      wise error rate (FWER) cluster-corrected). The protective haplotype was
      associated with increased FA in controls, but this effect was reversed in people
      with schizophrenia. White matter fiber tracking revealed that the region-of
      interest was traversed by portions of the superior longitudinal fasciculus,
      corona radiata, and posterior limb of internal capsule. Post hoc analysis
      revealed that reduced FA in this regional juncture correlated with reduced IQ in
      people with schizophrenia. The ST8SIA2 risk haplotype copy number did not show
      any differential effects on white matter. This study provides a link between a
      common disease-associated haplotype and specific changes in white matter
      microstructure, which may relate to resilience or risk for mental illness,
      providing further compelling evidence for involvement of ST8SIA2 in the
      pathophysiology of schizophrenia.

PMID- 29353882
TI  - IGF1R signaling drives antiestrogen resistance through PAK2/PIX activation in
      luminal breast cancer.
AB  - Antiestrogen resistance in estrogen receptor positive (ER+) breast cancer is
      associated with increased expression and activity of insulin-like growth factor 1
      receptor (IGF1R). Here, a kinome siRNA screen has identified 10 regulators of
      IGF1R-mediated antiestrogen with clinical significance. These include the
      tamoxifen resistance suppressors BMPR1B, CDK10, CDK5, EIF2AK1, and MAP2K5, and
      the tamoxifen resistance inducers CHEK1, PAK2, RPS6KC1, TTK, and TXK. The p21
      activated kinase 2, PAK2, is the strongest resistance inducer. Silencing of the
      tamoxifen resistance inducing genes, particularly PAK2, attenuates IGF1R-mediated
      resistance to tamoxifen and fulvestrant. High expression of PAK2 in ER+
      metastatic breast cancer patients is correlated with unfavorable outcome after
      first-line tamoxifen monotherapy. Phospho-proteomics has defined PAK2 and the PAK
      interacting exchange factors PIXalpha/beta as downstream targets of IGF1R
      signaling, which are independent from PI3K/ATK and MAPK/ERK pathways. PAK2 and
      PIXalpha/beta modulate IGF1R signaling-driven cell scattering. Targeting
      PIXalpha/beta entirely mimics the effect of PAK2 silencing on antiestrogen re
      sensitization. These data indicate PAK2/PIX as an effector pathway in IGF1R
      mediated antiestrogen resistance.

PMID- 29353883
TI  - Growth arrest and apoptosis induction in androgen receptor-positive human breast
      cancer cells by inhibition of USP14-mediated androgen receptor deubiquitination.
AB  - It has been well known that androgen receptor (AR) is critical to prostate cancer
      development and progression. It has also been documented that AR is expressed in
      more than 60% of breast tumors, which promotes the growth of estrogen receptor
      negative (ER-)/AR-positive (AR+) breast cancer cells. Thus, AR might be a
      potential therapeutic target for AR-positive/ER-negative breast cancer patients.
      Previously we reported that in prostate cancer cells proteasome-associated
      deubiquitinase ubiquitin-specific protease 14 (USP14) stabilized AR protein level
      by removing its ubiquitin chain. In the current study, we studied the USP14-AR
      protein interaction and cell proliferation status after USP14 reduction or
      inhibition in breast cancer cells, and our results support the conclusion that
      targeting USP14 is a novel strategy for treating AR-responsive breast cancer. We
      found that inhibition of USP14 accelerated the K48-ubiquitination and proteasome
      mediated degradation of AR protein. Additionally, both genetic and
      pharmacological inhibition of USP14 significantly suppressed cell proliferation
      in AR-responsive breast cancer cells by blocking G0/G1 to S phase transition and
      inducing apoptosis. Moreover, AR overexpression inhibited USP14 inhibition
      induced events, suggesting that AR deubiquitination by USP14 is critical for
      breast cancer growth and USP14 inhibition is a possible strategy to treat AR
      positive breast cancer.

PMID- 29353884
TI  - MicroRNA-146b promotes PI3K/AKT pathway hyperactivation and thyroid cancer
      progression by targeting PTEN.
AB  - Recent studies have shown that miR-146b is the most upregulated microRNA in
      thyroid cancer and has a central role in cancer progression through mechanisms
      that remain largely unidentified. As phosphoinositide 3-kinase/protein kinase-B
      (PI3K/AKT) signaling is a fundamental oncogenic driver in many thyroid cancers,
      we explored a potential role for miR-146b and its target genes in PI3K/AKT
      activation. Among the predicted target genes of miR-146b, we found the tumor
      suppressor phosphatase and tensin homolog (PTEN). Constitutive overexpression of
      miR-146b in thyroid epithelial cell lines significantly decreased PTEN mRNA and
      protein levels by direct binding to its 3'-UTR. This was accompanied by PI3K/AKT
      hyperactivation, leading to the exclusion of FOXO1 and p27 from the nucleus and a
      corresponding increase in cellular proliferation. Moreover, miR-146b
      overexpression led to protection from apoptosis and an increased migration and
      invasion potential, regulating genes involved in epithelial-mesenchymal
      transition. Notably, with the single exception of E-cadherin expression, all of
      these outcomes could be reversed by PTEN coexpression. Further analysis showed
      that miR-146b directly inhibits E-cadherin expression through binding to its 3'
      UTR. Interestingly, miR-146b inhibition in human thyroid tumor xenografts, using
      a synthetic and clinically amenable molecule, blocked tumor growth when delivered
      intratumorally. Importantly, this inhibition increased PTEN protein levels. In
      conclusion, our data define a novel mechanism of PI3K/AKT hyperactivation and
      outline a regulatory role for miR-146b in suppressing PTEN expression, a frequent
      observation in thyroid cancer. Both events are related to a more aggressive
      tumoral phenotype. Targeting miR-146b therefore represents a promising
      therapeutic strategy for the treatment of this disease.

PMID- 29353885
TI  - CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and
      survival of human mucoepidermoid carcinoma cells.
AB  - Mucoepidermoid carcinoma (MEC) arises in many glandular tissues and contributes
      to the most common malignant salivary gland cancers. MEC is specifically
      associated with a unique t(11;19) translocation and the resulting CRTC1-MAML2
      fusion is a major oncogenic driver for MEC initiation and maintenance. However,
      the molecular basis underlying the CRTC1-MAML2 oncogenic functions remains
      elusive. Through gene expression profiling analysis, we observed that LINC00473,
      a long non-coding RNA (lncRNA), was the top down-regulated target in CRTC1-MAML2
      depleted human MEC cells. LncRNAs belong to a new class of non-coding RNAs with
      emerging roles in tumorigenesis and progression, but remain poorly characterized.
      In this study, we investigated the role of LINC00473 in mediating CRTC1-MAML2
      oncogenic activity in human MEC. We found that LINC00473 transcription was
      significantly induced in human CRTC1-MAML2-positive MEC cell lines and primary
      MEC tumors, and was tightly correlated with the CRTC1-MAML2 RNA level. LINC00473
      induction was dependent on the ability of CRTC1-MAML2 to activate CREB-mediated
      transcription. Depletion of LINC00473 significantly reduced the proliferation and
      survival of human MEC cells in vitro and blocked the in vivo tumor growth in a
      human MEC xenograft model. RNA in situ hybridization analysis demonstrated a
      predominantly nuclear localization pattern for LINC00473 in human MEC cells.
      Furthermore, gene expression profiling revealed that LINC00473 depletion resulted
      in differential expression of genes important in cancer cell growth and survival.
      LINC00473 likely regulates gene expression in part through its ability to bind to
      a cAMP signaling pathway component NONO, enhancing the ability of CRTC1-MAML2 to
      activate CREB-mediated transcription. Our overall results demonstrate that
      LINC00473 is a downstream target and an important mediator of the CRTC1-MAML2
      oncoprotein. Therefore, LINC00473 acts as a promising biomarker and therapeutic
      target for human CRTC1-MAML2-positive MECs.

PMID- 29353886
TI  - The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax)
      by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double
      hit lymphoma.
AB  - High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, mostly
      known as double-hit lymphoma (DHL), is a rare entity characterized by morphologic
      and molecular features between Burkitt lymphoma and the clinically manageable
      diffuse large B-cell lymphoma (DLBCL). DHL patients usually undergo a rapidly
      progressing clinical course associated with resistance to standard chemo
      immunotherapy. As a consequence, the prognosis of this entity is particularly
      poor with a median overall survival inferior to 1 year. ABT-199 (venetoclax) is a
      potent and selective small-molecule antagonist of BCL-2 recently approved for the
      treatment of a specific subtype of lymphoid neoplasm. In this study, we
      demonstrate that single-agent ABT-199 efficiently displaces BAX from BCL-2
      complexes but fails to maintain a significant antitumor activity over time in
      most MYC+/BCL2+DHL cell lines and primary cultures, as well as in a xenograft
      mouse model of the disease. We further identify the accumulation of the BCL2-like
      protein BFL-1 to be a major mechanism involved in acquired resistance to ABT-199.
      Noteworthy, this phenomenon can be counteracted by the BET bromodomain inhibitor
      CPI203, since gene expression profiling identifies BCL2A1, the BFL-1 coding gene,
      as one of the top apoptosis-related gene modulated by this compound. Upon CPI203
      treatment, simultaneous downregulation of MYC and BFL-1 further overcomes
      resistance to ABT-199 both in vitro and in vivo, engaging synergistic caspase
      mediated apoptosis in DHL cultures and tumor xenografts. Together, these findings
      highlight the relevance of BFL-1 in DH lymphoma-associated drug resistance and
      support the combined use of a BCL-2 antagonist and a BET inhibitor as a promising
      therapeutic strategy for patients with aggressive DHL.

PMID- 29353888
TI  - Palliative Care in Resource-poor Settings: Inequalities, Challenges, and
      Opportunities.
AB  - N/A.

PMID- 29353889
TI  - Public Health Interventions for Control of Malaria in the Population Living in
      the Terai Region of Nepal.
AB  - Infectious diseases are a major problem for developing countries. Controlling and
      eradicating these diseases have remained a challenge because of the multitudes of
      social and environmental factors involved. However, a multi-sectoral and
      collective effort in dealing with these diseases has been shown to result in
      positive outcomes. This paper looks at the current situation of Malaria in Nepal
      and a population that is at high risk. It explains the impact that social and
      environmental determinants have on this target population. This review then
      critically examines the various possible public health interventions that could
      potentially help in the control of malaria in this high risk population, drawing
      from evidences and experiences reported from other countries with suggestions for
      adapting these interventions to the Nepali environment.

PMID- 29353887
TI  - P11 promoter methylation predicts the antidepressant effect of electroconvulsive
      therapy.
AB  - Although electroconvulsive therapy (ECT) is among the most effective treatment
      options for pharmacoresistant major depressive disorder (MDD), some patients
      still remain refractory to standard ECT practise. Thus, there is a need for
      markers reliably predicting ECT non/response. In our study, we have taken a novel
      translational approach for discovering potential biomarkers for the prediction of
      ECT response. Our hypothesis was that the promoter methylation of p11, a
      multifunctional protein involved in both depressive-like states and
      antidepressant treatment responses, is differently regulated in ECT responders
      vs. nonresponders and thus be a putative biomarker of ECT response. The chronic
      mild stress model of MDD was adapted with the aim to obtain rats that are
      resistant to conventional antidepressant drugs (citalopram). Subsequently,
      electroconvulsive stimulation (ECS) was used to select responders and
      nonresponders, and compare p11 expression and promoter methylation. In the rat
      experiments we found that the gene promoter methylation and expression of p11
      significantly correlate with the antidepressant effect of ECS. Next, we
      investigated the predictive properties of p11 promoter methylation in two
      clinical cohorts of patients with pharmacoresistant MDD. In a proof-of-concept
      clinical trial in 11 patients with refractory MDD, higher p11 promoter
      methylation was found in responders to ECT. This finding was replicated in an
      independent sample of 65 patients with pharmacoresistant MDD. This translational
      study successfully validated the first biomarker reliably predicting the
      responsiveness to ECT. Prescreening of this biomarker could help to identify
      patients eligible for first-line ECT treatment and also help to develop novel
      antidepressant treatment procedures for depressed patients resistant to all
      currently approved antidepressant treatments.

PMID- 29353890
TI  - Safety and Efficacy of Intravenous Ferric Carboxy Maltose in Iron Deficiency
      Anaemia During Post-partum Period.
AB  - BACKGROUND: Iron deficiency is the commonest treatable cause of postpartum
      anaemia. Parenteral iron therapy results in faster and higher replenishment of
      iron stores and correction of haemoglobin levels with better compliance. Ferric
      Carboxy Maltose is an effective and a safe option which can be administered
      intravenously in single total correction dose without any serious adverse
      effects.The study was done to evaluate the efficacy and safety of Ferric Carboxy
      Maltose in the treatment of iron deficiency anaemia in post-natal patients.
      METHODS: It was an open, single arm study including 615 women with diagnosis of
      Iron deficiency anaemia and haemoglobin (Hb) levels between 4gm% and 11gm% from
      January 2013 to December 2016. Intravenous Ferric Carboxy Maltose(500-1500mg) was
      administered and the improvement in haemoglobin levels and iron stores were
      assessed after three weeks of total dose infusion. RESULTS: Out of the 615 women,
      595 women were included in the analysis. Most of the women were in the age group
      of 27-30 years. Most of the women had mild anaemia as per World Health
      Organisation guidelines. Mean hemoglobin levels significantly increased over a
      period of three weeks after Ferric Carboxy Maltose administration. Other
      parameters like total iron binding capacity, Ferritin and Iron also had a
      significant improvement after Ferric Carboxy Maltose administration. No serious
      adverse events were observed after Ferric Carboxy Maltose. CONCLUSIONS:
      Intravenous Ferric Carboxy Maltose was an effective and a safe treatment option
      for iron deficiency anaemia and has an advantage of single administration of high
      doses without serious adverse effects.

PMID- 29353891
TI  - Knowledge, Attitude, and Practice on Menstrual Hygiene Management among School
      Adolescents.
AB  - BACKGROUND: Menstrual hygiene management remains a taboo in many communities in
      Nepal. Cultural beliefs about menstruation such as food taboos and untouchability
      have negative impact on dignity, health and education of adolescent girls. The
      objective of the study was to assess the current knowledge, attitude and practice
      of school adolescents on menstrual hygiene management in Doti District in Far
      Western Nepal. METHODS: This cross-sectional study was carried out from October
      to December 2016 at seven village development committees in Doti district, Nepal.
      This study was done among 276 students from grade seven and eight of 11 schools.
      Self-administered structured questionnaire was used to obtain information from
      school students. Descriptive analysis was done to analyse the knowledge, attitude
      and practice of school adolescents on menstrual hygiene management. RESULTS:
      67.4% respondents had fair knowledge and 26.4% respondents had good knowledge on
      menstrual hygiene management. However, out of 141 female adolescent respondents,
      only 56 (40%) were engaged in good menstrual hygiene practices. Around half of
      the respondents had positive attitude towards menstrual hygiene management
      related issues. CONCLUSIONS: Although knowledge on menstrual hygiene management
      among school adolescents is fair, still attitude and practice need to improve.
      Findings indicate the need of behavior change communication campaigns along with
      frequent reinforcement of school health education programs.

PMID- 29353892
TI  - Magnetic Resonance Imaging Findings in Spondylodiscitis.
AB  - BACKGROUND: Magnetic Resonance Imaging is the imaging modality of choice for
      imaging spinal infection due to its high sensitivity and specificity. This study
      aims to study the magnetic resonance imaging changes in patients with
      spondylodiscitis. METHODS: The study was a retrospective study carried in a
      multimodality imaging centre in Kathmandu. Magnetic resonance imaging records and
      clinical record of 3 years duration were reviewed and patients with clinical and
      radiological diagnosis of spondylodiscitis were included in the study. Three
      radiologists interpreted Magnetic Resonance Imaging with mutual consensus in
      disputed issues. Data analysis was done with Statistical Package for Social
      Sciences21.0. RESULTS: A total of 52 patients were included in the study. The
      mean age of the patients was 43.9 +/- 17.6 years. Spondylodiscitis involved
      lumbar spine in 26(50%) case, cervical and thoracic spine in 13(25%) cases each.
      Multiple IV discs were involved in 24(46.2%) cases, which was most common in
      cervical spine and least common in thoracic spine. Only one vertebral end plate
      was involved in 16(30.8%) cases. Epidural collection was seen in 23(44.2%) cases
      and paravertebral collection was noted in 63(33.5%) cases. Statistical
      significant difference in region of spine involved (p=0.02) and epidural
      collection (p=0.04) was noted between genders. CONCLUSIONS: Lumbar spine was the
      most common level involved with spondylodiscitis, perivertebral enhancing soft
      tissue was present in all cases, and involvement of disc and the endplates were
      the most common pattern.

PMID- 29353893
TI  - Organ Dysfunctions among Deaths in Critically Ill Patients.
AB  - BACKGROUND: Multiple organ failure is recognized as the final pathway preceding
      majority of deaths in intensive care unit. This study aims to find out the
      prevalence of organ dysfunctions/ failures in patients at the time of their
      demise irrespective of the underlying diseases in a tertiary care hospital.
      METHODS: This study was done in medical intensive care unit of Blue Cross
      Hospital. Medical records of all deceased patients in two years period were
      thoroughly reviewed retrospectively. Status of six organ systems was categorized
      into five sub-groups: No organ dysfunction, Mild organ dysfunction, Acute organ
      failure, Acute-on-chronic organ failure, and Chronic organ failure. The
      proportion of organ dysfunction involved was analyzed along with other variables.
      RESULTS: Among 204 deaths, majority 165 (80.9%) had Multiple Organ Dysfunction
      Syndrome. Circulatory system was most affected system with "acute organ failure"
      134 (65.5%) followed by acute respiratory failure 128 (62.7%), and acute
      neurologic failure 114 (55.8%). Neurologic system was most affected with "mild
      organ dysfunction" 47 (23%) followed by Respiratory system and Renal system. Of
      the patients who had chronic organ failures at the time of admission, 72 (81.8%)
      developed "acute-on-chronic failures". CONCLUSIONS: Multiple Organ Dysfunction
      Syndrome was present in the majority of deaths in critically ill patients. Most
      common acutely failed organ was the circulatory system.

PMID- 29353894
TI  - Factors Associated with the Utilization of Institutional Delivery Service among
      Mothers.
AB  - BACKGROUND: Assessment of utilization of institutional delivery services is
      crucial to reduce risk of maternal mortality and morbidity in countries like
      Nepal. This study was conducted to find out the proportion of utilization of
      institutional delivery service and associated factors among mothers. METHODS:
      Data was collected from the total of 129 mothers of Kathar VDC, Chitwan district
      who delivered baby within last one year proceeding the period of data collection
      using census method. Descriptive statistics and binary logistic regression
      analysis were applied. RESULTS: Out of 129 mothers, 78.3% had their delivery in
      the health facilities. Binary logistic analysis showed number of factors
      associated with utilization of institutional delivery service such as ethnicity,
      respondents educational level, number of pregnancy, number of ANC visit and birth
      preparedness status. But in the multivariable logistic regression analysis, no.
      of ANC visit (AOR = 10.03, 95 % CI = 1.02-98.29) was only independent factors
      affecting institutional delivery service utilization. CONCLUSIONS: A number of
      factors have been shown to affect the utilization of institutional delivery.
      Therefore, concerned authority should plan and implement awareness programme
      aiming at increasing antenatal clinic visits and utilization of institutional
      delivery service.

PMID- 29353895
TI  - Workplace Violence and its Associated Factors among Nurses.
AB  - BACKGROUND: Workplace violence among nurses is prevalent worldwide. If nurses
      become aware of the workplace violence and its risk factors then only they can
      protect themselves. This study assessed the prevalence of workplace violence and
      its associated factors among nurses in Pokhara, Nepal. METHODS: A hospital-based
      descriptive cross-sectional study was conducted in Pokhara. The required sample
      size of the study was 200 nurses. We adopted self-administered questionnaire
      developed by International Labor Office, International Council of Nurses, World
      Health Organization (WHO), and Public Services International. Out of 21 hospitals
      of Pokhara, we selected five hospitals using simple random sampling method. The
      number of nurses in each hospital was fixed proportionately considering the total
      number of employed nurses. Individual nurses were selected on the first meet
      first basis to gain the required number. RESULTS: Two-thirds (64.5%) nurses
      experienced some type of violence in the last six months at their workplace. The
      proportion of verbal violence was higher (61.5%) compared to the physical (15.5%)
      and sexual violence (9%). Most perpetrators of the violence were the relatives of
      patients and hospital employees. Age of nurses and working stations had
      statistically significant association with workplace violence (p-value < 0.05).
      CONCLUSIONS: Workplace violence among nurses is a noteworthy problem in Pokhara
      whereas nearly two-thirds of nurses faced some type of violence in last six
      months. It is an urge to widen awareness level of nurses on the violence thus,
      they can take precaution themselves and ask hospital administration and other
      stakeholders to address the workplace violence.

PMID- 29353896
TI  - Prevalence and Awareness of Hypertension among Adults and its Related Risk
      Factors.
AB  - BACKGROUND: Hypertension is a modifiable risk factor for cardiovascular diseases.
      Various studies conducted in the world showed high prevalence of hypertension,
      which is in increasing trend in Nepal also. The aim of this study was to assess
      hypertension status and risk behaviours among adult population in Kirtipur
      Municipality. METHODS: A cross sectional descriptive study was conducted among
      580 adults of age 20 - 59 from December 2015 to April 2016. Data was collected by
      observation method to determine hypertension prevalence and Body Mass Index.
      Questionnaire was used to assess exposure to the risk factors. RESULTS: Among all
      hypertension prevalence was 37.0% (215 out of 580). The prevalence was 41.6% (110
      out of 264) among male and 32.2% (105 out of 316) among female (P <0.03 at 95%
      CI). Among 215 hypertensives, 37.2% were not aware about themselves having
      hypertension. Within last 12 months, 453 (78.1%) participants had checked their
      blood pressure. Proportion of hypertension was increasing with higher BMI and
      advancing age. Among all, 136 (23.7%) were current smokers, and 58.1% among them
      had hypertension. CONCLUSIONS: This study indicated that hypertension prevalence
      was high among adults in Kirtipur municipality. Prevalence of smoking was also
      high, and among them hypertension prevalence was very high. About one-third
      participants with hypertension were not aware that they had hypertension. Habit
      of doing regular physical exercise was very low.

PMID- 29353897
TI  - Oral Cancer Knowledge and Awareness in Patients Visiting Kantipur Dental College.
AB  - BACKGROUND: Lack of knowledge and awareness about oral cancer, its risk factors
      and negligence of the early warning signs play crucial role in raising the
      incidence of the disease. The present study was carried out to evaluate the
      awareness of oral cancer among patients visiting Kantipur Dental College,
      Kathmandu, Nepal. METHODS: The cross-sectional study was done in 471 patients
      from 15-85 years. Self administered questionnaire was prepared which comprised of
      knowledge of oral cancer, source of information, its early signs and symptoms
      along with the awareness of its risk factors. RESULTS: Most of the participants
      (41.80%) had not heard of oral cancer. 31.60% recognized tobacco smoking and
      tobacco chewing as the chief risk factor with 15.50% and 10.80% of participants
      who identified white patch and red patch as early sign of oral cancer
      respectively. Pearson's chi square test was used which showed statistically
      significant association of total mean knowledge score and awareness score with
      age, education level and occupation (p<0.05). CONCLUSIONS: This study done in
      dental patients showed lack of knowledge and awareness in general public about
      oral cancer. There seem to be a need for more planned awareness programs through
      newspapers, radio, television and health campaigns regarding the association of
      habits in the development of oral cancer and benefits of detecting oral cancer at
      early stage for better prognosis.

PMID- 29353898
TI  - Motivational Profiles of Medical Students of Nepalese Army Institute of Health
      Sciences.
AB  - BACKGROUND: Students enter the medical study with different types of motives.
      Given the importance of academic motivation for good academic achievement of the
      students, the present study was designed to reveal the possible relationship
      between academic motivation and achievement in medical students. METHODS: In this
      cross-sectional study medical students (N=364) of Nepalese Army institute of
      Health Sciences were participated and classified to different subgroups using
      intrinsic and controlled motivation scores. Cluster membership was used as an
      independent variable to assess differences in study strategies and academic
      performance. RESULTS: Four clusters were obtained: High Intrinsic High
      Controlled, Low Intrinsic High Controlled, High Intrinsic Low Controlled, and Low
      Intrinsic Low Controlled. High Intrinsic High Controlled and High Intrinsic Low
      Controlled profile students constituted 36.1%, 22.6% of the population,
      respectively. No significant differences were observed as regards to deep
      strategy and surface strategy between high interest status motivated and high
      interest-motivated students. However, both of the clusters had significantly
      deeper, surface strategy and better academic performance than status-motivated
      and low-motivation clusters (p < 0.001). CONCLUSIONS: The interest status
      motivated and interest-motivated medical students were associated with good deep
      and surface study strategy and good academic performance. Low-motivation and
      status-motivated students were associated with the least academic performance
      with less interest learning behaviors. This reflected that motivation is
      important required component for good learning outcomes for medical students
      Keywords: Academic performance; controlled motivation; clusters; intrinsic
      motivation; motivation.

PMID- 29353899
TI  - Assessing Caregiver Burden in Caregivers of Patients with Schizophrenia and
      Bipolar Affective Disorder in Kathmandu Medical College.
AB  - BACKGROUND: Schizophrenia and bipolar affective disorder are chronic psychiatric
      illness that requires long term care. This study tends to measure psychological
      burden and factors associated with it among caregivers of these two illnesses.
      METHODS: This is a cross- sectional study that included participants by purposive
      sampling method. Self designed performa was used to collect the socio-demographic
      details of the caregivers. Modified caregiver strain index was used to assess the
      overall stress. Beck's depression inventory and Beck's anxiety inventory was used
      to assess depression and anxiety respectively. RESULTS: Hundred caregivers, 50
      each of schizophrenia and bipolar affective disorder were enrolled. Seventy-two
      percent of caregivers were found to have higher level of stress. Twenty-five
      percent had depression and 29% anxiety related problems. Stress was found to be
      significantly associated with being in debt, longer duration of illness,
      education level, marital status, subjective feeling of psychological stress and
      self- acknowledgement of need of professional help. Caregivers of both group
      experienced similar level of stress. CONCLUSIONS: Psychological burden is seen to
      be high in caregivers of patients of Schizophrenia and Bipolar Affective
      Disorder.

PMID- 29353900
TI  - Prevalence of Tuberculosis in Patients with Liver Cirrhosis.
AB  - BACKGROUND: Studies have shown that patients with liver cirrhosis are more
      susceptible to tuberculosis because of immune dysfunction; however there are only
      limited data. We carried out this study to know the prevalence and clinical
      characteristics of tuberculosis in patients with liver cirrhosis. METHODS: In
      this retrospective study, medical files of 200 consecutive patients admitted with
      diagnosis of liver cirrhosis in the medical ward of liver unit, Bir Hospital from
      January 2011 to December 2014 were evaluated for the presence of TB and clinical
      characteristics of these patients were analyzed. RESULTS: Eighteen patients were
      diagnosed to have tuberculosis with a prevalence of 9%. The median age of
      patients with tuberculosis and liver cirrhosis was 53 (35-71) years and M: F
      ratio was 2:1. 67%, P=0.01). Median CTP score of patients were 8.5 (5-12) (CTP A:
      B: C: 3:7:8). Extra pulmonary tuberculosis was more common (67%) than pulmonary
      (33%). In extra pulmonary tuberculosis, distribution was as pleural effusion
      (n=4), abdominal (n=4), intestinal (n=2), peritoneal (n=9), and pott's spine
      (n=2). CONCLUSIONS: Tuberculosis is prevalent in patients with liver cirrhosis.
      Extra pulmonary tuberculosis was more compared to pulmonary tuberculosis.
      Tuberculosis was common in decompensated liver cirrhosis than compensated liver
      cirrhosis .

PMID- 29353901
TI  - Tuberculosis in Staff and Students of Patan Hospital.
AB  - BACKGROUND: There is a high risk of occupational exposure to tuberculosis among
      healthcare workers in endemic countries. Regular screening for tuberculosis among
      healthcare workers is not carried out in Nepal. Infection control measures are
      also not routinely implemented. The aim of this study was to determine the
      prevalence of active tuberculosis among staff/students at Patan Hospital.
      METHODS: Participants were given a self-administered questionnaire and invited to
      undergo chest radiography. Cases were scored and reviewed based on predetermined
      criteria, and presumptive tuberculosis cases were invited to undergo sputum smear
      and culture. Participants were categorized according to the extent of patient
      contact and asked about history of tuberculosis medication. RESULTS: Among 560
      participants, 76.8% had direct contact with patients. Fifty-eight (10.4%) gave
      history of cough >2 weeks. Based on symptom history and chest radiography, 20.0%
      (n=112) cases were reviewed, and 12.5% (n=14) of those reviewed had sputum tested
      for acid-fast bacilli. One participant had culture-positive tuberculosis. Fifty
      participants (8.9%) reported tuberculosis in the past, among which 42.0% (n=21)
      occurred after employment at Patan Hospital and 42.0% before joining Patan
      Hospital. Security staff, radiology technicians and ward cleaning staff had the
      highest proportion of cases with a history of tuberculosis.History of
      tuberculosis medication had no relation with age, sex, education, body mass index
      and smoking.The incidence rate of tuberculosis at Patan Hospital was 3.6 per 1000
      person-years. CONCLUSIONS: Overall incidence of tuberculosis among healthcare
      workers is noteworthy. However, this study suggests when symptomatic tuberculosis
      occurs in healthcare worker at Patan Hospital, it is diagnosed and there is not a
      large pool of undiagnosed tuberculosis.

PMID- 29353902
TI  - Knowledge, Attitude and Practice towards Kangaroo Mother Care.
AB  - BACKGROUND: Kangaroo mother care is an effective and low cost technique which
      prevents neonate from hypothermia, a leading cause of preventable neonatal
      mortality. Knowledge and practice of Kangaroo mother care is of utmost importance
      in developing countries such as Nepal. Purpose of this study was to find out
      knowledge, attitude and practice of kangaroo mother care among health workers in
      tertiary health centres in Nepal. METHODS: This cross sectional study was carried
      out in three teaching hospitals in Nepal during the period from January 2016 to
      April 2016. Doctors and nurses working in Paediatrics/Neonatal and
      Obstetrics/Gynaecology wards were surveyed using pretested questionnaire.
      Responses from the doctors and the nurses were compared. RESULTS: Response rate
      of the survey was 65%. All of the doctors and 95.3% of the nurses who
      participated in the survey had knowledge about kangaroo mother care.37.7%of the
      doctors and 48.8% of the nurses thought that this method is only used for
      neonates with low birth weight (<2500grams) (p= 0.013).Three fourth of the
      doctors and half of the nurses agreed that KMC is practiced regularly in their
      ward (p = 0.016). 22.2% participants informed that main reasons for not
      practicing kangaroo care regularly could be lack of skill and knowledge.
      CONCLUSIONS: We found that general knowledge and attitude of majority of doctors
      and nurses towards kangaroo mother care was good, however, its practise was not
      uniform.

PMID- 29353903
TI  - Evaluation of Endotracheal Tube Cuff Pressure in Laparoscopic Cholecystectomy and
      Postoperative Sore Throat.
AB  - BACKGROUND: The use of nitrous oxide and carboperitoneum in laparoscopic
      cholecystectomy lead to increase in endotracheal tube cuff pressure. It may
      impair tracheal mucosal perfusion with subsequent tracheal damage. The purpose of
      this study was to evaluate cuff pressure and incidence of post-operative sore
      throat in patients undergoing laparoscopic cholecystectomy. METHODS: In this
      prospective observational study, 128 patients aged 18-65 years of American
      Society of Anesthesiologist physical status I and II undergoing laparoscopic
      cholecystectomy were enrolled and allocated alternately into two groups, Study
      Group (Maintenance of anesthesia with sevoflurane 1-2%, oxygen/nitrous oxide
      mixture; 40/60), Control Group (Maintenance of anesthesia with sevoflurane 1-2%,
      oxygen/air mixture; 40/60) were analysed and comapared. Each group contained 64
      patients. Aneroid manometer was used to monitor cuff pressure. Volume of air used
      to inflate the cuff, baseline cuff pressure, comparison of intraoperative cuff
      pressure and incidence of post-operative sore throat were measured. RESULTS: The
      study results demonstrated higher cuff pressure in study group at all times after
      the creation of carboperitoneum (p=0.00) with increased incidence of sore
      throat(p=0.004). CONCLUSIONS: Increase in endotracheal tube cuff pressure was
      noted with the use of nitrous oxide in laparoscopic cholecystectomy with
      subsequent post-operative airway complication. Monitoring of cuff pressure is
      simple, noninvasive and efficient way of achieving therapeutic cuff pressure of
      20-30 cm of H2O and thus recommends its use.

PMID- 29353904
TI  - Differences in Return of Spontaneous Circulation in Early vs Late Endotracheal
      Intubation among Patients in Hospital Cardiac Arrest.
AB  - BACKGROUND: Common airway management strategies during cardiopulmonary
      resuscitation are bag- mask-valve ventilation followed by endotracheal
      intubation. Timing of endotracheal intubation is controversial. This study was
      designed to compare the effect of early vs late endotracheal intubation in terms
      of return of spontaneous circulation. METHODS: This is an observational
      retrospective study done at tertiary center for the period of two years. The
      study population was inpatient, adult and pediatric with witnessed cardiac arrest
      in whom airway management was initially done with bag-valve-mask ventilation
      followed by endotracheal intubation. Timing of intubations were grouped into
      early and late with cut off time of five minutes and the groups were compared in
      terms of return of spontaneous circulation. RESULTS: There were total of 193
      patients included in the study. Early intubation was done in 114 patients
      (59.06%) and late intubation was done in 79 patients (40.94%). Mean time for
      early intubation was 3.11 minutes. Mean time for late intubation was 7.89
      minutes. Seventy three patients (37.8%) attained sustained ROSC. Thirty five
      patients (30.7%) achieved ROSC in early intubation group while 38 patients
      (48.1%) attained sustained ROSC in late intubation group(p = 0.016). CONCLUSIONS:
      Early intubation during cardiopulmonary resuscitation was associated with lower
      rate of return of spontaneous circulation.

PMID- 29353905
TI  - Critical Appraisal of Published Literature in Specialty General Surgical
      Examinations in the United Kingdom.
AB  - The specialty general surgical examination in the United Kingdom, which needs to
      be qualified by the higher surgical trainees towards the end of their training
      prior to assuming consultant responsibility, includes "academic foundation viva"
      as a mandatory component. This section of examination is intended to assess
      candidate's ability to critically appraise published literature with regards to
      its validity and clinical relevance, which is essential requirement for a surgeon
      to be able to deliver care to his patients based on robust evidence collected
      from properly conducted studies. The paper aims to outline the objectives of the
      assessment process, the details of appraisal methodology and techniques to
      acquire the skill.

PMID- 29353906
TI  - Caesarean Scar Endometriosis.
AB  - Endometriosis is a common benign gynecologic disorder defined as the presence of
      endometrial glands and stroma outside of the normal location. The overall
      prevalence is 8-15% in women of reproductive age group. Scar endometriosis is a
      rare disease, and is difficult to diagnose. It is commonly seen following
      obstetrical and gynecological surgeries. The symptoms are non-specific, typically
      involving abdominal wall pain at the incision site at the time of menstruation
      and palpable tender mass in the incision site. The diagnosis is frequently made
      only after excision of the diseased tissue and its histological analysis. We
      present here a case of abdominal wall scar endometriosis in a woman who had
      undergone a caesarean section four years ago. Surgical excision led to the
      diagnosis of scar endometriosis. The pathogenesis, diagnosis and treatment of
      this rare condition are discussed.

PMID- 29353907
TI  - Tungiasis: A Rare Parasitic Infestation in Genitals of a Native Male from
      Kathmandu.
AB  - Tungiasis is a common parasitic infection inmany parts of the world, including
      South and Central America and parts of Africa. It is rare in other places, such
      as in India and Pakistan and imported cases have been reported in Taiwan, Italy,
      the United States of America, etc. Our diagnosis was made based on
      histopathologiocal features of the parasite, which corresponds too ther reports
      and description of tungiasis.1-3 It was treated by surgical excision alone. The
      fact that the disease has never been reported in Nepal makes it difficult to
      diagnose clinically, but should be considered in the future. Histopathology can
      aid in diagnosingthis rare condition.

PMID- 29353908
TI  - Partial Invasive Mole with Bilateral Torsion of Theca Lutein Cysts.
AB  - Gestational trophoblastic neoplasia is extremely rare entity accounting 1% of all
      gynecological malignancies. Invasive mole is a form of Gestational trophoblastic
      neoplasia which is locally invasive with propensity of metastasis. Association of
      partial mole with invasive mole and/or theca lutein cysts is a rare occurrence.
      Large cysts may present with complications. A case with these rare combinations
      presented at 15+3 weeks period of gestation as acute abdomen due to torsion of
      bilateral theca lutein cysts is reported. Right salpingo-ophorectomy with
      untwisting of left cyst was done. Six cycles of chemotherapy was given with
      regular betahCG monitoring. First trimester dating scan would have helped in
      early diagnosis, treatment and prevention of complications.

PMID- 29353909
TI  - Medical Errors in Autopsied Cases.
AB  - N/A.

PMID- 29353910
TI  - Parasite dispersal risk tolerance is mediated by its reproductive value.
AB  - Parasite dispersal theory draws heavily upon epidemiological SIR models in which
      host status (susceptible (S), infected (I), or recovered (R)) is used to study
      parasite dispersal evolution. In contrast to these extrinsically host-centric
      drivers, in this study we focus on an intrinsic driver, the parasite's
      reproductive value (predicted future offspring) as a regulator of the extent to
      which the individual will engage in risky dispersal behaviour. As a model system
      we use the honeybee Apis mellifera and its ectoparasite, the mite Varroa
      destructor. Mite reproduction happens exclusively inside cells of bee brood, and
      newly emerged fecund mites may parasitize either a homocolonial brood cell (low
      risk dispersal) or emigrate to a new bee colony via phoretic attachment to mature
      forager bees (high risk dispersal). In an empirical bioassay, prepartum mites
      (high reproductive value) and postpartum mites (low reproductive value) were
      offered a choice of newly emerged homocolonial worker bees (low risk),
      homocolonial pollen forager bees (high risk), or heterocolonial pollen foragers
      (high risk). A preference for newly emerged bees was earlier and more strongly
      sustained among prepartum mites. This suggests comparatively greater dispersal
      risk tolerance among postpartum mites with lower reproductive value. A dangerous
      bid for dispersal may be adaptive if the individual has already successfully
      reproduced and the rewards for successful dispersal are sufficiently large.

PMID- 29353911
TI  - Miscellanea Dependent generalized functional linear models.
AB  - This paper considers testing for no effect of functional covariates on response
      variables in multivariate regression. We use generalized estimating equations to
      determine the underlying parameters and establish their joint asymptotic
      normality. This is then used to test the significance of the effect of predictors
      on the vector of response variables. Simulations demonstrate the importance of
      considering existing correlation structures in the data. To explore the effect of
      treating genetic data as a function, we perform a simulation study using gene
      sequencing data and find that the performance of our test is comparable to that
      of another popular method used in sequencing studies. We present simulations to
      explore the behaviour of our test under varying sample size, cluster size and
      dimension of the parameter to be estimated, and an application where we are able
      to confirm known associations between nicotine dependence and neuronal nicotinic
      acetylcholine receptor subunit genes.

PMID- 29353912
TI  - Simultaneously Quantifying Ferrihydrite and Goethite in Natural Sediments Using
      the Method of Standard Additions with X-ray Absorption Spectroscopy.
AB  - The presence of ferrihydrite in sediments/soils is critical to the cycling of
      iron (Fe) and many other elements but difficult to quantify. Extended X-ray
      absorption fine structure (EXAFS) spectroscopy has been used to speciate Fe in
      the solid phase, but this method is thought to have difficulties in
      distinguishing ferrihydrite from goethite and other minerals. In this study, both
      conventional EXAFS linear combination fitting (LCF) and the method of standard
      additions are applied to the same samples in attempt to quantify ferrihydrite and
      goethite more rigorously. Natural aquifer sediments from Bangladesh and the
      United States were spiked with known quantities of ferrihydrite, goethite and
      magnetite, and analyzed by EXAFS. Known mineral mixtures were also analyzed.
      Evaluations of EXAFS spectra of mineral references and EXAFS-LCF fits on various
      samples indicate that ferrihydrite and microcrystalline goethite can be
      distinguished and quantified by EXAFS-LCF but that the choice of mineral
      references is critical to yield consistent results. Conventional EXAFS-LCF and
      the method of standard-additions both identified appreciable amount of
      ferrihydrite in Bangladesh sediments that were obtained from a low-arsenic
      Pleistocene aquifer. Ferrihydrite was also independently detected by sequential
      extraction and 57Fe Mossbauer spectroscopy. These observations confirm the
      accuracy of conventional EXAFS-LCF and demonstrate that combining EXAFS with
      additions of reference materials provides a more robust means of quantifying
      short-range-ordered minerals in complex samples.

PMID- 29353913
TI  - Mathematics Content Coverage and Student Learning in Kindergarten.
AB  - Analyzing data from two nationally representative kindergarten cohorts, we
      examine the mathematics content teachers cover in kindergarten. We expand upon
      prior research, finding that kindergarten teachers report emphasizing basic
      mathematics content. Although teachers reported increased coverage of advanced
      content between the 1998-99 and 2010-11 school years, they continued to place
      more emphasis on basic content. We find that time on advanced content is
      positively associated with student learning, whereas time on basic content has a
      negative association with learning. We argue that increased exposure to more
      advanced mathematics content could benefit the vast majority of kindergartners.

PMID- 29353914
TI  - MASS TRANSFER IN THE ENTRANCE REGION OF A CIRCULAR TUBE.
AB  - A solution in the form of an asymptotic expansion is obtained for the problem of
      mass transfer in the entrance region of a circular tube or flat channel for
      arbitrary hydrodynamically-developed velocity profile and arbitrary dependence of
      the diffusion coefficient on the coordinate perpendicular to the flow. Boundary
      conditions of the first, second and third kind are considered. The results of the
      analysis are compared with known approximate and numerical solutions of similar
      problems.

PMID- 29353915
TI  - Reference correlations for the thermal conductivity of liquid copper, gallium,
      indium, iron, lead, nickel and tin.
AB  - The available experimental data for the thermal conductivity of liquid copper,
      gallium, indium, iron, lead, nickel, and tin has been critically examined with
      the intention of establishing thermal conductivity reference correlations. All
      experimental data have been categorized into primary and secondary data according
      to the quality of measurement specified by a series of criteria. The proposed
      standard reference correlations for the thermal conductivity of liquid copper,
      gallium, indium, iron, lead, nickel, and tin are respectively characterized by
      uncertainties of 9.8, 15.9, 9.7, 13.7, 16.9, 7.7, and 12.6% at the 95% confidence
      level.

PMID- 29353916
TI  - Synthesis and characterization of novel ferrocenyl chalcone ammonium and
      pyridinium salt derivatives.
AB  - A novel series of ferrocenyl chalcone ammonium and pyridinium salt derivatives
      were synthesized in order to improve their solubility in aqueous media.
      Substituted ferrocenyl chalcones with amines and pyridines were synthesized using
      the base-catalyzed Claisen-Schmidt reaction, and their corresponding salts were
      prepared by a nucleophilic quaternization reaction at the nitrogen atom. Most of
      the synthesized ferrocenyl chalcone salts were soluble in water at room
      temperature. They were fully characterized by IR, NMR spectroscopy and HRMS
      spectrometry, and their electrochemistry was studied. The salt derivatives
      presented chemical reversibility, electrochemical quasi reversibility, and the
      slope of a plot of Log Ipc (or Ipa) versus Log v were almost 0.5 suggesting that
      their redox process was controlled by diffusion.

PMID- 29353918
TI  - A new regime of Pauli-spin blockade.
AB  - Pauli-spin blockade (PSB) is a transport phenomenon in double quantum dots that
      allows for a type of spin to charge conversion often used to probe fundamental
      physics such as spin relaxation and singlet-triplet coupling. In this paper, we
      theoretically explore Pauli-spin blockade as a function of magnetic field B
      applied parallel to the substrate. In the well-studied low magnetic field regime,
      where PSB occurs in the forward (1, 1) -> (0, 2) tunneling direction, we
      highlight some aspects of PSB that are not discussed in detail in existing
      literature, including the change in size of both bias triangles measured in the
      forward and reverse biasing directions as a function of B. At higher fields, we
      predict a crossover to "reverse PSB" in which current is blockaded in the reverse
      direction due to the occupation of a spin singlet as opposed to the traditional
      triplet blockade that occurs at low fields. The onset of reverse PSB coincides
      with the development of a tail like feature in the measured bias triangles and
      occurs when the Zeeman energy of the polarized triplet equals the exchange energy
      in the (0, 2) charge configuration. In Si quantum dots, these fields are
      experimentally accessible; thus, this work suggests a way to observe a crossover
      in magnetic field to qualitatively different behavior.

PMID- 29353917
TI  - Sculpting Metal-binding Environments in De Novo Designed Three-helix Bundles.
AB  - De novo protein design is a biologically relevant approach used to study the
      active centers of native metalloproteins. In this review, we will first discuss
      the design process in achieving alpha3D, a de novo designed three-helix bundle
      peptide with a well-defined fold. We will then cover our recent work in
      functionalizing the alpha3D framework by incorporating a tris(cysteine) and
      tris(histidine) motif. Our first design contains the thiol-rich sites found in
      metalloregulatory proteins that control the levels of toxic metal ions (Hg, Cd,
      and Pb). The latter design recapitulates the catalytic site and activity of a
      natural metalloenzyme carbonic anhydrase. The review will conclude with future
      design goals aimed at introducing an asymmetric metal-binding site in the alpha3D
      framework.

PMID- 29353919
TI  - Measurements of Enthalpy of Sublimation of Ne, N2, O2, Ar, CO2, Kr, Xe, and H2O
      using a Double Paddle Oscillator.
AB  - We report precise experimental values of the enthalpy of sublimation (DeltaHs )
      of quenched condensed films of neon (Ne), nitrogen (N2), oxygen (O2), argon (Ar),
      carbon dioxide (CO2), krypton (Kr), xenon (Xe), and water (H2O) vapor using a
      single consistent measurement platform. The experiments are performed well below
      the triple point temperature of each gas and fall in the temperature range where
      existing experimental data is very limited. A 6 cm2 and 400 um thick double
      paddle oscillator (DPO) with high quality factor (Q ~ 4 * 105 at 298K) and high
      frequency stability (33 parts per billion) is utilized for the measurements. The
      enthalpies of sublimation are derived by measuring the rate of mass loss during
      temperature programmed desorption. The mass change is detected due to change in
      the resonance frequency of the self-tracking oscillator. Our measurements
      typically remain within 10% of the available literature, theory, and National
      Institute of Standards and Technology (NIST) Web Thermo Tables (WTT) values, but
      are performed using an internally consistent method across different gases.

PMID- 29353920
TI  - Ethnic Differences in Returning Home: Explanations From a Life Course
      Perspective.
AB  - Ethnic differences in leaving and returning home may reflect varying cultural
      norms regarding intergenerational coresidence, but also differences in
      transitions in linked domains, for example, employment and partnership
      transitions. This study uses Dutch population register data to compare returning
      home among second-generation Turks, Moroccans, Surinamese, and Antilleans with
      native Dutch who had left the parental home between age 16 and 28 in the period
      1999 to 2011 (N = 194,020). All second-generation groups were found to be more
      likely to return home than native Dutch. A large part of these differences was
      related to the timing and occurrence of other key events in the life course, such
      as age at leaving home and partnership dissolution. Although the impact of
      partnership dissolution on returning home was found to be strong among all origin
      groups, it was less pronounced among second-generation youth, particularly Turks
      and Moroccans, than native Dutch youth. Possible explanations and implications
      are discussed.

PMID- 29353921
TI  - Chemical Signals of Vector Beetle Facilitate the Prevalence of a Native Fungus
      and the Invasive Pinewood Nematode.
AB  - In China, the invasive Bursaphelenchus xylophilus, the vector Monochamus
      alternatus beetle, and associated fungi exhibit a symbiotic relationship causing
      serious losses to pine forests. Although this complex system has been intensively
      investigated, the role of vector beetles on the development of associated fungi
      and their indirect contribution to the prevalence of pinewood nematode (PWN) is
      yet unknown. Here, three of the highly prevalent fungal species, viz., Sporothrix
      sp. 1, Ophiostoma ips, and Sporothrix sp. 2 were isolated from beetle chambers in
      diseased trees in Guangdong province, southeast China. Pairwise cultivation of
      isolated fungi demonstrated the dominance of Sporothrix sp. 1 over O. ips and
      Sporothrix sp. 2. On the other hand, two fatty acid ethyl esters (FAEE), ethyl
      palmitate (EP) and ethyl linoleate (EL), isolated from the body surface of the
      vector beetle enhanced the growth of Sporothrix sp. 1. When PWN were cultured on
      Sporothrix sp. 1, the fecundity and the body length were increased significantly
      as compared with when cultured on O. ips and Sporothrix sp. 1. Our results
      suggest that the vector beetles promote Sporothrix sp. 1 to occupy more niches by
      rapid growth and spread, which in turn better support PWN population, hence
      facilitate PWN pathogenicity in the invasive regions.

PMID- 29353922
TI  - Modeling Host-Microbiome Interactions in Caenorhabditis elegans.
AB  - The microbiome influences host processes including nutritional availability,
      development, immunity, and behavioral responses. Caenorhabditis elegans is a
      powerful model to study molecular mechanisms of host-microbial interactions.
      Recent efforts have been made to profile the natural microbiome of C. elegans,
      laying a foundation for mechanistic studies of host-microbiome interactions in
      this genetically tractable model system. Studies using single-species microbes,
      multi-microbial systems, and humanized worm-microbiome interaction studies reveal
      metabolic and microbial-microbial interactions relevant in higher organisms. This
      article discusses recent developments in modeling the effects of host-microbiome
      interactions in C. elegans.

PMID- 29353925
TI  - First Report of Estonian Cyst Nematode Cactodera estonica from India.

PMID- 29353924
TI  - Secondary Metabolites Produced by Heterorhabditis Symbionts and Their Application
      in Agriculture: What We Know and What to Do Next.
AB  - Gram-negative Photorhabdus bacteria have a dual lifestyle: they are mutualists of
      Heterorhabditis nematodes and are pathogens of insects. Together, this nematode
      bacterium partnership has been used to successfully control a wide range of
      agricultural insect pests. Photorhabdus produce a diverse array of small
      molecules that play key biological roles in regulating their dual roles. In
      particular, several secondary metabolites (SM) produced by this bacterium are
      known to play a critical role in the maintenance of a monoxenic infection in the
      insect host and are also known to prevent contamination of the cadaver from soil
      microbes and/or predation by arthropods. A few of the SM this bacteria produce
      have been isolated and identified, and their biological activities have also been
      tested in laboratory assays. Over the past two decades, analyses of the genomes
      of several Photorhabdus spp. have revealed the presence of SM numerous gene
      clusters that comprise more than 6% of these bacteria genomes. Furthermore,
      genome mining and characterization of biosynthetic pathways, have uncovered the
      richness of these compounds, which are predicted to vary across different
      Photorhabdus spp. and strains. Although progress has been made in the
      identification and function of SM genes and gene clusters, the targeted testing
      for the bioactivity of molecules has been scarce or mostly focused on medical
      applications. In this review, we summarize the current knowledge of Photorhabdus
      SM, emphasizing on their activity against plant pathogens and parasites. We
      further discuss their potential in the management of agricultural pests and the
      steps that need to be taken for the implementation of Photorhabdus SM in pest
      management.

PMID- 29353926
TI  - Oat, Wheat, and Sorghum Genotype Reactions to Meloidogyne incognita and
      Meloidogyne javanica.
AB  - Meloidogyne spp. are the most economically important species of plant-pathogenic
      nematodes. Plant resistance and crop rotation are the main nematode management
      methods. Thus, the objective was to evaluate the resistance of seven wheat
      genotypes, five oat genotypes, ten sorghum hybrids, and three sorghum-sudangrass
      genotypes to Meloidogyne incognita and Meloidogyne javanica. The crops were sowed
      in pots with an autoclaved substrate. A single plant/pot was left after thinning.
      The soil was infested with 5,000 eggs of the studied nematodes. Tomato (cv.
      Rutgers) plants were used as the standard for nematode susceptibility. The
      evaluations were conducted 60 d after inoculation. Gall and egg-mass indexes were
      obtained according to a 0-5 scale. Plants with a reproduction factor higher than
      1.0 were classified as susceptible (S) and lower than 1.0 as resistant (R). Wheat
      and oat genotypes did not allow M. incognita and M. javanica reproduction,
      proving resistance to these organisms. Sorghum genotypes had different reactions
      to M. incognita and M. javanica. The tomato (cv. Rutgers) plants demonstrated the
      viability of the nematode inoculum for the three crops. The wheat and oat
      genotypes and the sorghum hybrids 'BRS-610', 'BRS-800', and '307.343' can be used
      in crop rotation systems for M. incognita and M. javanica management.

PMID- 29353927
TI  - First Report of Matricidal Hatching in Bursaphelenchus xylophilus.
AB  - The reproductive strategy of the pinewood nematode (PWN), Bursaphelenchus
      xylophilus, is sexual amphimictic and oviparous. The incidence of intrauterine
      egg development and hatching in plant-parasitic nematodes is not a very common
      phenomenon. During the process of maintaining and breeding a B. xylophilus
      population isolated in Spain under laboratory conditions, evidence of matricidal
      hatching was observed. This is the first described case of this phenomenon in
      this species.

PMID- 29353928
TI  - First Reports, Morphological, and Molecular Characterization of Longidorus
      caespiticola and Longidorus poessneckensis (Nematoda: Longidoridae) from Ukraine.
AB  - Seven needle nematode species of the genus Longidorus have been reported in
      Ukraine. Nematological surveys for needle nematodes were carried out in Ukraine
      between 2016 and 2017 and two nematode species of Longidorus (L. caespiticola and
      L. poessneckensis) were collected from natural and anthropogenically altered
      habitats on the territory of Opillia and Zakarpattia in Ukraine. Nematodes were
      extracted from 500 cm3 of soil by modified sieving and decanting method.
      Extracted specimens were processed to glycerol and mounted on permanent slides
      and subsequently identified morphologically and molecularly. Nematode DNA was
      extracted from single individuals and PCR assays were conducted as previously
      described for D2-D3 expansion segments of 28S rRNA. Sequence alignments for D2-D3
      from L. caespiticola showed 97%-99% similarity to other sequences of L.
      caespiticola deposited in GenBank from Belgium, Bulgaria, Czech Republic, Russia,
      Slovenia, and Scotland. Similarly, D2-D3 sequence alignments from L.
      poessneckensis, showed 99% to other sequences of L. poessneckensis deposited in
      GenBank from Slovakia and Czech Republic. Morphology, morphometry, and molecular
      data obtained from these samples were consistent with L. caespiticola and L.
      poessneckensis identification. To our knowledge, these are the first reports of
      L. caespiticola and L. poessneckensis in Ukraine, extending the geographical
      distribution of these species.

PMID- 29353923
TI  - A Model for Evolutionary Ecology of Disease: The Case for Caenorhabditis
      Nematodes and Their Natural Parasites.
AB  - Many of the outstanding questions in disease ecology and evolution call for
      combining observation of natural host-parasite populations with experimental
      dissection of interactions in the field and the laboratory. The "rewilding" of
      model systems holds great promise for this endeavor. Here, we highlight the
      potential for development of the nematode Caenorhabditis elegans and its close
      relatives as a model for the study of disease ecology and evolution. This
      powerful laboratory model was disassociated from its natural habitat in the
      1960s. Today, studies are uncovering that lost natural history, with several
      natural parasites described since 2008. Studies of these natural Caenorhabditis
      parasite interactions can reap the benefits of the vast array of experimental and
      genetic tools developed for this laboratory model. In this review, we introduce
      the natural parasites of C. elegans characterized thus far and discuss resources
      available to study them, including experimental (co)evolution, cryopreservation,
      behavioral assays, and genomic tools. Throughout, we present avenues of research
      that are interesting and feasible to address with caenorhabditid nematodes and
      their natural parasites, ranging from the maintenance of outcrossing to the
      community dynamics of host-associated microbes. In combining natural relevance
      with the experimental power of a laboratory supermodel, these fledgling host
      parasite systems can take on fundamental questions in evolutionary ecology of
      disease.

PMID- 29353929
TI  - First Report of Cactodera estonica in Canada.
AB  - A population of cyst nematode with terminal protuberance was found in soil
      samples associated with and on the roots of Polygonum aviculare L. at N45 degrees
      23.480', W75 degrees 40.463' in South Ottawa, Ontario. Both J2 and cysts were
      found. It was subsequently confirmed with morphological and molecular methods as
      Cactodera estonica Krall and Krall, 1978 (Krall and Krall, 1978). The cysts are
      dark brown, elongated with length/breadth ratio more than 2, and vulval fenestra
      circumfenestrate 33 +/- 4.1 (20-48) um in diameter. Vulval slit is short 16 +/-
      2.7 (13-20) um. Not all cysts have bullae or underbridge, when present a few
      bullae scattered on the ventral side of the cyst wall and the underbridge is
      thin; vulval denticles were found in one specimen. Male not found. J2
      measurements are body length at 505 +/- 45 (420-630) um, stylet 25 +/- 4.4 (22
      29) um long, and tail 36 +/- 3.1 (34-38) um with a short hyaline portion 14 +/-
      3.0 (12-19) um. Lateral fields with four incisures. Tail end is round. All of
      these are consistent with those of C. estonica, for which the elongated cyst and
      short hyaline in J2 are characteristic for the species. Ribosomal DNA of the ITS,
      18S, and D2/D3 of 28S regions were PCR amplified from cysts and J2s using primers
      18S (5'-TTGATTACGTCCCTGCCCTTT-3') and 26S (5'-TTTCACTCGCCGTTACTAAGG-3') (Vrain et
      al., 1992), D2A (5'-ACAAGTACCGTGAGGGAAAGT-3') (Nunn, 1992) and D3B (5'
      GACCCGTCTTGAAACACGGA-3') (De Ley et al., 1999), and sequenced. The sequences of
      the ITS and D2/D3 regions of 1,480 and 1,363 bps, respectively, were deposited in
      Genbank with accession numbers MF774482 and MF774483. When blasted in to the NCBI
      database (August 2017), the ITS sequence was 99% similar to sequences of
      AF274417, a population of C. estonica from Belgium and of KX579922 from Turkey,
      and the D2/D3 sequence was 99% similar to sequences of HM560797 and HM560796,
      populations of C. estonica from China. This is the first reported case of this
      nematode species in Canada and the second for the western hemisphere (Norgren and
      Golden, 1986).

PMID- 29353930
TI  - Xiphinema japonicum n. sp. (Nematoda: Longidorinae) from the Rhizosphere of
      Japanese Podocarpus macrophyllus (Thunb.), a Cryptic Species Related to Xiphinema
      bakeri Williams, 1961.
AB  - Xiphinema japonicum n. sp., isolated in Ningbo, China, from the rhizosphere of
      Podocarpus macrophyllus (Thunb.) imported from Japan is described. The new
      species belongs to Xiphinema non-americanum group 7 and is characterized by
      medium body length (3.0-3.7 mm), total stylet length 190-201 MUm, vulva located
      anteriorly (V = 30.5%-35.3%), two equally developed female genital branches
      without uterine differentiation (no Z or pseudo-Z organ and/or spines in the
      uteri), short tail, convex-conoid with subdigitate peg in terminus, and absence
      of males. The species has four juvenile developmental stages (J1 was not found).
      The polytomous identification codes of the new species are (codes in parentheses
      are exceptions) A4-B4-C4-D5(4)-E2(3)-F3(4)-G2(3)-H2-I3-J4-K?-L1. Morphologically,
      the new species is mainly characterized by combination of the codes C4 and E2(3),
      making the species unique and different from other species in the genus. It is
      most similar to the North American species Xiphinema bakeri, herein considered as
      its cryptic species by the nature of high morphological similarity, but with
      significant differences in DNA sequences in nearly full length 18S, ITS1, 28S
      D2/D3, and cytochrome c oxidase subunit 1 sequences. The second morphologically
      close species is Xiphinema setariae from which the new species could be separated
      based on morphological and molecular characters. Morphological comparisons with
      phylogenetically related species are also discussed.

PMID- 29353931
TI  - Occurrence of Sheraphelenchus sucus (Nematoda: Aphelenchoidinae) and Panagrellus
      sp. (Rhabditida: Panagrolaimidae) Associated with Decaying Pomegranate Fruit in
      Italy.
AB  - Two different nematode species were recovered from pomegranate decaying fruit in
      two localities in Southern Italy: the mycetophagus nematode Sheraphelenchus sucus
      and a bacterial feeder nematode belonging to the Panagrolaimidae (Rhabditida)
      family. Morphometrics of the Italian population of S. sucus closely resemble that
      of the type population, whereas some differences were found when compared with
      another population from Iran. Molecular characterization of the Italian S. sucus
      using the 18S rRNA gene, D2-D3 expansion domains of the 28S rDNA, the ITS region,
      and the partial mitochondrial COI were carried out. Sequences of the 18S rRNA
      gene, the D2-D3 domains, and the ITS were analyzed using several methods for
      inferring phylogeny to reconstruct the relationships among Sheraphelenchus and
      Bursaphelenchus species. The bacterial feeder Panagrellus sp. was characterized
      at the molecular level only. The D2-D3 expansion domains and ITS sequences of
      this Italian panagrolaimid were determined. The D2-D3 sequences of the Italian
      panagrolaimid showed 99% similarity with the corresponding sequence of
      Panagrellus sp. associated with Rhynchophorus ferrugineus. This is the first
      report on the tritrophic association of S. sucus and Rhabditida that uses both
      insects and pomegranate fruit as hosts.

PMID- 29353932
TI  - Pathogenic Potential of Fresh, Frozen, and Thermally Treated Anisakis spp. Type
      II (L3) (Nematoda: Anisakidae) after Oral Inoculation into Wistar Rats: A
      Histopathological Study.
AB  - The third-stage (L3) larvae of Anisakis are the etiological agents of human
      anisakiasis caused by consumption of raw or undercooked seafood infected with
      anisakid nematodes. Infection with these worms is associated with abdominal pain,
      nausea, and diarrhea and can lead to massive infiltration of eosinophils and the
      formation of granulomas in the gastrointestinal tract if the larvae are not
      removed. Food allergy affects populations worldwide, and despite several reports
      on the presence of the potentially zoonotic nematodes among edible fishes in
      Egypt, there are few immunological and molecular studies investigating the
      epidemiology of these parasites. Anisakidosis, a human infection with nematodes
      of the family Anisakidae, is caused most commonly by Anisakis spp. In the present
      study, seventy specimens of the European seabass Dicentrarchus labrax
      commercialized in Alexandria city along the Mediterranean Sea were acquired
      during the period from July to December, 2015. Fish were necropsied and dissected
      to investigate the presence of nematode larvae. Thirty fish (42.9%) of the total
      were parasitized by nematode larvae which were morphologically identified as
      Anisakis spp. Type II (L3) according to light and scanning electron microscopy.
      The pathogenic potential of oral inoculation of fresh, frozen, and thermally
      treated larvae into Wistar rats was elucidated by histological examination of
      their thymus and spleen. Results obtained indicated that neither cooling nor
      freezing of the parasite could destroy their allergenic capacity. So, it is
      important to create a wider awareness of this potential risk to human health. It
      is becoming increasingly likely that the impact of Anisakis spp. on human health
      has been underestimated, and it is perhaps time to consider more sweeping
      measures than those currently enforced to protect the public health.

PMID- 29353933
TI  - Control of Globodera spp. Using Brassica juncea Seed Meal and Seed Meal Extract.
AB  - The eradication program for the potato cyst nematode (PCN), Globodera pallida, in
      the Northwest of the United States revolves around the use of soil fumigation.
      Alternative, integrated strategies are needed to continue to battle this invasive
      nematode. Laboratory, greenhouse, and field experiments were conducted with G.
      pallida and another cyst nematode found in the United States, Globodera
      ellingtonae, to evaluate the efficacy of a new formulated Brassica juncea seed
      meal extract, as well as a traditional B. juncea seed meal, as alternate
      eradication strategies. This is the first report on the efficacy of B. juncea
      seed meal extract against plant-parasitic nematodes. Rates of B. juncea seed meal
      greater than 2.2 t/ha and 4.5 t/ha for G. pallida and G. ellingtonae,
      respectively, were required for egg hatch suppression, as determined by a potato
      root diffusate (PRD) bioassay. Reproduction of G. pallida on potato after
      exposure to B. juncea seed meal at a rate of 2.2 t/ha was also significantly
      reduced. In the field, 8.9 t/ha B. juncea seed meal almost eliminated egg hatch
      of G. ellingtonae. Rates needed for Globodera spp. suppression were greatly
      reduced when using the B. juncea seed meal extract. When compared side-by-side,
      half as much B. juncea seed meal extract, 1.1 t/ha, was required to suppress G.
      ellingtonae egg hatch to the same extent as B. juncea seed meal. Exposure of G.
      pallida to B. juncea seed meal extract at 4.5 t/ha reduced egg hatch by 90%
      compared with a nonamended control. The ability to reduce the amount of material
      being applied to soil by using an extract has the potential for integration into
      a G. pallida eradication program.

PMID- 29353934
TI  - Annual and Perennial Alleyway Cover Crops Vary in Their Effects on Pratylenchus
      penetrans in Pacific Northwest Red Raspberry (Rubus idaeus).
AB  - Cover crops can provide many benefits to agroecosystems, such as lessening soil
      erosion and increasing water infiltration. However, cover crop use is not common
      in established red raspberry (Rubus idaeus) fields in the Pacific Northwest.
      Raspberry growers are concerned about resource competition between the cover crop
      and raspberry crop, as well as increasing population densities of the plant
      parasitic nematode Pratylenchus penetrans, which has a wide host range and has
      been shown to reduce raspberry plant vigor and yield. A 2-yr study was conducted
      in an established 'Meeker' raspberry field in northwest Washington to evaluate
      the effects of nine alleyway cover crops, mowed weed cover, and the industry
      standard of bare cultivated soil on P. penetrans population dynamics, raspberry
      yield, and fruit quality. The host status for P. penetrans of cover crops
      included in the field experiment, as well as Brassica juncea 'Pacific Gold' and
      Sinapis alba 'Ida Gold', was also evaluated in greenhouse experiments. In the
      field experiment, P. penetrans population densities did not increase in alleyway
      cover crop roots over time or in alleyway soil surrounding cover crop roots
      (means range from 0 to 116 P. penetrans/100 g of soil) compared with the bare
      cultivated control (means range from 2 to 55 P. penetrans/100 g of soil).
      Pratylenchus penetrans populations did not increase over time in raspberry grown
      adjacent to alleyways with cover crops (means range from 1,081 to 6,120 P.
      penetrans/g of root) compared with those grown adjacent to bare cultivated soil
      alleyways (means range from 2,391 to 5,536 P. penetrans/g of root). Raspberry
      grown adjacent to bare cultivated soil did not have significantly higher yield or
      fruit quality than raspberry grown adjacent to cover crops in either year of the
      experiment. In the greenhouse assays, 'Norwest 553' wheat and a perennial
      ryegrass mix were poor hosts for P. penetrans, whereas 'Nora' and 'TAM 606' oat
      and 'Pacific Gold' and 'Ida Gold' mustard were good hosts. These results support
      the idea that the potential benefits of alleyway cover crops outweigh the
      potential risk of increasing P. penetrans population densities and do not
      compromise raspberry yield or fruit quality.

PMID- 29353935
TI  - Susceptibility of Seven Caladium (Caladium * hortulanum) Cultivars to Meloidogyne
      arenaria, M. enterolobii, M. floridensis, M. incognita, and M. javanica.
AB  - There is no known root-knot nematode (Meloidogyne spp.) resistance in caladium
      (Caladium * hortulanum), an ornamental foliage crop grown from tubers, but
      cultivars have been reported to differ in their level of susceptibility. Research
      was conducted to assess the relative susceptibility of seven widely grown
      caladium cultivars to the species of Meloidogyne which occur in the southeastern
      United States, where caladium cultivars are commonly planted in commercial and
      residential landscapes. Root-knot nematode species tested were Meloidogyne
      arenaria, Meloidogyne enterolobii (=M. mayaguensis), Meloidogyne floridensis,
      Meloidogyne incognita, and Meloidogyne javanica. All of the caladium cultivars
      tested were susceptible to galling by all species of Meloidogyne tested; however
      M. javanica caused the least severe galling. Meloidogyne enterolobii produced
      high numbers of eggs per gram of fresh root on all cultivars tested, with cv.
      Freida Hemple having the highest number (14,799 eggs/g fresh root). Meloidogyne
      javanica also reproduced at a high level on most cultivars tested. Overall, the
      number of eggs of M. arenaria, M. floridensis, and M. incognita was low on all
      caladium cultivars tested. Meloidogyne javanica was isolated from caladium roots
      in high numbers regardless of the cultivar. Meloidogyne incognita had low numbers
      of second stage root-knot nematode juveniles (J2) isolated from soil of all
      cultivars. The high level of reproduction of M. enterolobii and the high rate of
      isolation of M. javanica from roots, as well as the low rate of isolation of M.
      incognita from soil, are not reflected in gall ratings where M. javanica ratings
      were low but high numbers of eggs and J2 were present in roots. An increased
      understanding of cultivar susceptibility levels and the reproductive capacity of
      common root-knot nematode on caladium under various environmental conditions is
      needed to better manage nematode-infested planting sites and improve caladium
      growth.

PMID- 29353936
TI  - Chemosensory Responses of Plant Parasitic Nematodes to Selected Phytochemicals
      Reveal Long-Term Habituation Traits.
AB  - Plant parasitic nematodes (PPN) are important crop pests within the global agri
      sector. Critical to their success is a complex and highly sensitive chemosensory
      system used to locate plants by detecting host cues. In addition to this, the
      nematode neuronal system has evolved mechanisms to allow adaptation to a changing
      environment. Clearly, there is a need to better understand the host-parasite
      relationship and the mechanisms by which PPN successfully locate and infect host
      plants. Here, we demonstrate the chemotactic response of two economically
      important PPN species, Meloidogyne incognita and Globodera pallida to selected
      phytochemicals. We further reveal an adapted chemotactic response in M. incognita
      second-stage juveniles preexposed to ethephon (Eth), potato root diffusate (PRD),
      and salicylic acid (SA), and present pharmacological evidence supporting the
      existence of long-term habituation traits acting via serotonergic-dependent
      neurotransmission.

PMID- 29353937
TI  - An Investigation of the Potential Antifungal Properties of CNC-2 in
      Caenorhabditis elegans.
AB  - Caenorhabditis elegans responds to infections by upregulating specific
      antimicrobial peptides. The caenacin-2 (cnc-2) gene is consistently upregulated
      in C. elegans by infection with the filamentous fungus Drechmeria coniospora, but
      there have been no direct studies of the CNC-2 peptide's in vivo or in vitro role
      in defending the nematode against this pathogen. We compared infection of wild
      type and cnc-2 knockout nematode strains with four potential pathogens: D.
      coniospora, Candida albicans, Staphylococcus aureus, and Bacillus subtilis. There
      was no significant difference in survival between strains for any of the
      pathogens or on the maintenance strain of Escherichia coli. While we were unable
      to demonstrate definitively that CNC-2 is integral to fungal defenses in C.
      elegans, we identified possible explanations for these results as well as future
      work that is needed to investigate CNC-2's potential as a new antifungal
      treatment.

PMID- 29353940
TI  - A Mathematical Model of Countercurrent Exchange of Oxygen Between Paired
      Arterioles and Venules.
AB  - A mathematical model is formulated for diffusive countercurrent exchange of
      oxygen between paired arterioles and venules. A closed form solution of the
      problem is obtained by linearizing the nonlinear oxyhemoglobin dissociation curve
      at the inlet PO2 in the vessel. The closed form solution is compared with the
      corresponding numerical solution of the nonlinear problem. Under normal
      conditions, longitudinal gradients of venular PO2 are found to be small. Examples
      are presented where the model predicts significant gradients of venular PO2 when
      the blood flow rate in the venule is several times smaller than that in the
      arteriole.

PMID- 29353939
TI  - Multi-Stimuli-Responsive Amphiphilic Assemblies through Simple Postpolymerization
      Modifications.
AB  - A strategy to construct different stimuli responsive polymers from post
      polymerization modifications of a single polymer scaffold via thiol-disulfide
      exchange has been developed. Here, we report on a random copolymer that enables
      the design and syntheses of a series of dual or multi-stimuli responsive
      nanoassemblies using a simple post-polymerization modification step. The reactive
      functional group involves a side chain monopyridyl disulfide unit, which rapidly
      and quantitatively reacts with various thiols under mild conditions. Independent
      and concurrent incorporation of physical, chemical or biologically responsive
      properties have been demonstrated. We envision that this strategy may open up
      opportunities to simplify the synthesis of multi-functional polymers with broad
      implications in a variety of biological applications.

PMID- 29353941
TI  - A Bayesian model selection approach for identifying differentially expressed
      transcripts from RNA sequencing data.
AB  - Recent advances in molecular biology allow the quantification of the
      transcriptome and scoring transcripts as differentially or equally expressed
      between two biological conditions. Although these two tasks are closely linked,
      the available inference methods treat them separately: a primary model is used to
      estimate expression and its output is post processed by using a differential
      expression model. In the paper, both issues are simultaneously addressed by
      proposing the joint estimation of expression levels and differential expression:
      the unknown relative abundance of each transcript can either be equal or not
      between two conditions. A hierarchical Bayesian model builds on the BitSeq
      framework and the posterior distribution of transcript expression and
      differential expression is inferred by using Markov chain Monte Carlo sampling.
      It is shown that the model proposed enjoys conjugacy for fixed dimension
      variables; thus the full conditional distributions are analytically derived. Two
      samplers are constructed, a reversible jump Markov chain Monte Carlo sampler and
      a collapsed Gibbs sampler, and the latter is found to perform better. A cluster
      representation of the aligned reads to the transcriptome is introduced, allowing
      parallel estimation of the marginal posterior distribution of subsets of
      transcripts under reasonable computing time. Under a fixed prior probability of
      differential expression the clusterwise sampler has the same marginal posterior
      distributions as the raw sampler, but a more general prior structure is also
      employed. The algorithm proposed is benchmarked against alternative methods by
      using synthetic data sets and applied to real RNA sequencing data. Source code is
      available on line from https://github.com/mqbssppe/cjBitSeq.

PMID- 29353942
TI  - Analytic posteriors for Pearson's correlation coefficient.
AB  - Pearson's correlation is one of the most common measures of linear dependence.
      Recently, Bernardo (11th International Workshop on Objective Bayes Methodology,
      2015) introduced a flexible class of priors to study this measure in a Bayesian
      setting. For this large class of priors, we show that the (marginal) posterior
      for Pearson's correlation coefficient and all of the posterior moments are
      analytic. Our results are available in the open-source software package JASP.

PMID- 29353938
TI  - Watching Proteins Function with Time-resolved X-ray Crystallography.
AB  - Macromolecular crystallography was immensely successful in the last two decades.
      To a large degree this success resulted from use of powerful third generation
      synchrotron X-ray sources. An expansive database of more than 100,000 protein
      structures, of which many were determined at resolution better than 2 A, is
      available today. With this achievement, the spotlight in structural biology is
      shifting from determination of static structures to elucidating dynamic aspects
      of protein function. A powerful tool for addressing these aspects is time
      resolved crystallography, where a genuine biological function is triggered in the
      crystal with a goal of capturing molecules in action and determining protein
      kinetics and structures of intermediates (Schmidt et al., 2005a; Schmidt 2008;
      Neutze and Moffat, 2012; Srajer 2014). In this approach, short and intense X-ray
      pulses are used to probe intermediates in real time and at room temperature, in
      an ongoing reaction that is initiated synchronously and rapidly in the crystal.
      Time-resolved macromolecular crystallography with 100 ps time resolution at
      synchrotron X-ray sources is in its mature phase today, particularly for studies
      of reversible, light-initiated reactions. The advent of the new free electron
      lasers for hard X-rays (XFELs; 5-20 keV), which provide exceptionally intense,
      femtosecond X-ray pulses, marks a new frontier for time-resolved crystallography.
      The exploration of ultra-fast events becomes possible in high-resolution
      structural detail, on sub-picosecond time scales (Tenboer et al., 2014; Barends
      et al., 2015; Pande et al., 2016). We review here state-of-the-art time-resolved
      crystallographic experiments both at synchrotrons and XFELs. We also outline
      challenges and further developments necessary to broaden the application of these
      methods to many important proteins and enzymes of biomedical relevance.

PMID- 29353943
TI  - NONPARAMETRIC GOODNESS-OF-FIT TESTS FOR UNIFORM STOCHASTIC ORDERING.
AB  - We propose Lp distance-based goodness-of-fit (GOF) tests for uniform stochastic
      ordering with two continuous distributions F and G, both of which are unknown.
      Our tests are motivated by the fact that when F and G are uniformly
      stochastically ordered, the ordinal dominance curve R = FG-1 is star-shaped. We
      derive asymptotic distributions and prove that our testing procedure has a unique
      least favorable configuration of F and G for p ? [1,infinity]. We use simulation
      to assess finite-sample performance and demonstrate that a modified, one-sample
      version of our procedure (e.g., with G known) is more powerful than the one
      sample GOF test suggested by Arcones and Samaniego (2000, Annals of Statistics).
      We also discuss sample size determination. We illustrate our methods using data
      from a pharmacology study evaluating the effects of administering caffeine to
      prematurely born infants.

PMID- 29353944
TI  - Enhancement of phytoplankton chlorophyll by submesoscale frontal dynamics in the
      North Pacific Subtropical Gyre.
AB  - Subtropical gyres contribute significantly to global ocean productivity. As the
      climate warms, the strength of these gyres as a biological carbon pump is
      predicted to diminish due to increased stratification and depleted surface
      nutrients. We present results suggesting that the impact of submesoscale physics
      on phytoplankton in the oligotrophic ocean is substantial and may either
      compensate or exacerbate future changes in carbon cycling. A new statistical tool
      was developed to quantify surface patchiness from sea surface temperatures.
      Chlorophyll concentrations in the North Pacific Subtropical Gyre were shown to be
      enhanced by submesoscale frontal dynamics with an average increase of 38%
      (maximum of 83%) during late winter. The magnitude of this enhancement is
      comparable to the observed decline in chlorophyll due to a warming of ~1.1
      degrees C. These results highlight the need for an improved understanding of fine
      scale physical variability in order to predict the response of marine ecosystems
      to projected climate changes.

PMID- 29353946
TI  - Out-migration of Young Adults and Gender Division of Intergenerational Support in
      Rural China.
AB  - Using data from the baseline and follow-up surveys of "Well-being of Elderly in
      Anhui Province, China" conducted in 2001, in 2003 and in 2006, respectively, by
      the Institute for Population and Development Studies of Xi'an Jiaotong
      University, this paper employs random effects models to explore the gender
      division of intergenerational support in the elderly rural families. Analyses by
      parents' and children's gender suggest that there are gender differences in
      intergenerational support because of gender roles and division in family. Our
      analysis shows that older mothers receive more returns, which reciprocates their
      support, while older fathers benefit more from the out-migration of adult
      children. While sons take more responsibility for family support, daughters
      reciprocate support from their elderly parents more. Enhancement of the role and
      function of daughters in families has accompanied out-migration of young adults
      and suggests that gender differences in intergenerational supports between sons
      and daughters have decreased.

PMID- 29353947
TI  - Heterogeneity, Inequity Aversion, and Group Performance.
AB  - We investigate the effects of inequality in wealth on the incentives to
      contribute to a group output when agents are inequity averse and may differ in
      ability. We show that equality may lead to a reduction of contributions below
      levels generated by purely selfish agents. But introducing inequality motivates
      more productive agents to exert higher efforts and help the group to coordinate
      on equilibria with less free-riding. As a result, less able agents may benefit
      from initially disadvantageous inequality. Moreover, the more inequity averse the
      agents, the more inequality should be imposed even by an egalitarian social
      planner.

PMID- 29353945
TI  - On the analysis of complex biological supply chains: From Process Systems
      Engineering to Quantitative Systems Pharmacology.
AB  - The use of models in biology has become particularly relevant as it enables
      investigators to develop a mechanistic framework for understanding the operating
      principles of living systems as well as in quantitatively predicting their
      response to both pathological perturbations and pharmacological interventions.
      This application has resulted in a synergistic convergence of systems biology and
      pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence
      of quantitative systems pharmacology (QSP). In this review, we discuss how the
      foundational principles of chemical process systems engineering inform the
      progressive development of more physiologically-based systems biology models.

PMID- 29353948
TI  - A process-oriented perspective examining the relationships among daily coping,
      stress, and affect.
AB  - We assess the daily relationships between age, three functional coping
      strategies, and positive and negative affect while accounting for the
      individual's cognitive appraisal of the severity and controllability of their
      encountered stressor. We collected 56 days of daily data from participants in the
      Notre Dame Study of Healthy & Well-Being assessing affect, the most bothersome
      event experienced each day, and coping strategies used to deal with that event (N
      = 371; Age 44-87; M = 67.41; SD = 8.87). Multi-level modeling allowed us to
      explore and compare the between- and within-person effects. The main effects
      revealed that coping strategies relate to affect differently. The interaction
      terms revealed that the effectiveness of each coping strategy depended on
      characteristics of the encountered stressor and/or characteristics of the
      individual. Average values of stress severity, Altering the Meaning, and
      Dispelling the Effects more strongly related to PA or NA than daily fluctuations
      on these constructs. Findings illustrate that certain coping strategies target
      affect differently. Approaching research questions regarding stress and coping
      with a process-oriented perspective, through the use of daily data, allows for a
      more thorough understanding of the real-time, lived relationships among the
      individual, stress, and coping.

PMID- 29353949
TI  - Comparative Performance and Model Agreement of Three Common Photovoltaic Array
      Configurations.
AB  - Three grid-connected monocrystalline silicon arrays on the National Institute of
      Standards and Technology (NIST) campus in Gaithersburg, MD have been instrumented
      and monitored for 1 yr, with only minimal gaps in the data sets. These arrays
      range from 73 kW to 271 kW, and all use the same module, but have different
      tilts, orientations, and configurations. One array is installed facing east and
      west over a parking lot, one in an open field, and one on a flat roof. Various
      measured relationships and calculated standard metrics have been used to compare
      the relative performance of these arrays in their different configurations.
      Comprehensive performance models have also been created in the modeling software
      pvsyst for each array, and its predictions using measured on-site weather data
      are compared to the arrays' measured outputs. The comparisons show that all three
      arrays typically have monthly performance ratios (PRs) above 0.75, but differ
      significantly in their relative output, strongly correlating to their operating
      temperature and to a lesser extent their orientation. The model predictions are
      within 5% of the monthly delivered energy values except during the winter months,
      when there was intermittent snow on the arrays, and during maintenance and other
      outages.

PMID- 29353950
TI  - A HYBRID THREE-SCALE MODEL OF TUMOR GROWTH.
AB  - Cancer results from a complex interplay of different biological, chemical, and
      physical phenomena that span a wide range of time and length scales.
      Computational modeling may help to unfold the role of multiple evolving factors
      that exist and interact in the tumor microenvironment. Understanding these
      complex multiscale interactions is a crucial step towards predicting cancer
      growth and in developing effective therapies. We integrate different modeling
      approaches in a multiscale, avascular, hybrid tumor growth model encompassing
      tissue, cell, and sub-cell scales. At the tissue level, we consider the
      dispersion of nutrients and growth factors in the tumor microenvironment, which
      are modeled through reaction-diffusion equations. At the cell level, we use an
      agent based model (ABM) to describe normal and tumor cell dynamics, with normal
      cells kept in homeostasis and cancer cells differentiated apoptotic, hypoxic, and
      necrotic states. Cell movement is driven by the balance of a variety of forces
      according to Newton's second law, including those related to growth-induced
      stresses. Phenotypic transitions are defined by specific rule of behaviors that
      depend on microenvironment stimuli. We integrate in each cell/agent a branch of
      the epidermal growth factor receptor (EGFR) pathway. This pathway is modeled by a
      system of coupled nonlinear differential equations involving the mass laws of 20
      molecules. The rates of change in the concentration of some key molecules trigger
      proliferation or migration advantage response. The bridge between cell and tissue
      scales is built through the reaction and source terms of the partial differential
      equations. Our hybrid model is built in a modular way, enabling the investigation
      of the role of different mechanisms at multiple scales on tumor progression. This
      strategy allows representating both the collective behavior due to cell assembly
      as well as microscopic intracellular phenomena described by signal transduction
      pathways. Here, we investigate the impact of some mechanisms associated with
      sustained proliferation on cancer progression. Specifically, we focus on the
      intracellular proliferation/migration-advantage-response driven by the EGFR
      pathway and on proliferation inhibition due to accumulation of growth-induced
      stresses. Simulations demonstrate that the model can adequately describe some
      complex mechanisms of tumor dynamics, including growth arrest in avascular
      tumors. Both the sub-cell model and growth-induced stresses give rise to
      heterogeneity in the tumor expansion and a rich variety of tumor behaviors.

PMID- 29353951
TI  - Application of Chimera grid to modelling cell motion and aggregation in a narrow
      tube.
AB  - A computational scheme using the Chimera grid method is presented for simulation
      of three-dimensional motion and aggregation of two red blood cells (RBCs) in a
      narrow tube. The cells are modelled as rigid ellipsoidal particles; the
      computational scheme is applicable to deformable fluid-filled particles.
      Attractive energy between two RBCs is modelled by a depletion interaction theory
      and used for simulating aggregation of two cells. Through the simulation, we show
      that the Chimera grid method is applicable to the simulation of three-dimensional
      motion and aggregation of multiple RBCs in a microvessel and microvascular
      network.

PMID- 29353953
TI  - A Segmentation Editing Framework Based on Shape Change Statistics.
AB  - Segmentation is a key task in medical image analysis because its accuracy
      significantly affects successive steps. Automatic segmentation methods often
      produce inadequate segmentations, which require the user to manually edit the
      produced segmentation slice by slice. Because editing is time-consuming, an
      editing tool that enables the user to produce accurate segmentations by only
      drawing a sparse set of contours would be needed. This paper describes such a
      framework as applied to a single object. Constrained by the additional
      information enabled by the manually segmented contours, the proposed framework
      utilizes object shape statistics to transform the failed automatic segmentation
      to a more accurate version. Instead of modeling the object shape, the proposed
      framework utilizes shape change statistics that were generated to capture the
      object deformation from the failed automatic segmentation to its corresponding
      correct segmentation. An optimization procedure was used to minimize an energy
      function that consists of two terms, an external contour match term and an
      internal shape change regularity term. The high accuracy of the proposed
      segmentation editing approach was confirmed by testing it on a simulated data set
      based on 10 in-vivo infant magnetic resonance brain data sets using four
      similarity metrics. Segmentation results indicated that our method can provide
      efficient and adequately accurate segmentations (Dice segmentation accuracy
      increase of 10%), with very sparse contours (only 10%), which is promising in
      greatly decreasing the work expected from the user.

PMID- 29353952
TI  - Ruthenium PNN(O) Complexes: Cooperative Reactivity and Application as Catalysts
      for Acceptorless Dehydrogenative Coupling Reactions.
AB  - The novel tridentate PNNOH pincer ligand LH features a reactive 2-hydroxypyridine
      functionality as well as a bipyridyl-methylphosphine skeleton for meridional
      coordination. This proton-responsive ligand coordinates in a straightforward
      manner to RuCl(CO)(H)(PPh3)3 to generate complex 1. The methoxy-protected
      analogue LMe was also coordinated to Ru(II) for comparison. Both species have
      been crystallographically characterized. Site-selective deprotonation of the 2
      hydroxypyridine functionality to give 1' was achieved using both mild (DBU) and
      strong bases (KOtBu and KHMDS), with no sign of involvement of the
      phosphinomethyl side arm that was previously established as the reactive
      fragment. Complex 1' is catalytically active in the dehydrogenation of formic
      acid to generate CO-free hydrogen in three consecutive runs as well as for the
      dehydrogenative coupling of alcohols, giving high conversions to different esters
      and outperforming structurally related PNN ligands lacking the NOH fragment. DFT
      calculations suggest more favorable release of H2 through reversible reactivity
      of the hydroxypyridine functionality relative to the phosphinomethyl side arm.

PMID- 29353954
TI  - Assessing personality in San Joaquin kit fox in situ: efficacy of field-based
      experimental methods and implications for conservation management.
AB  - Utilisation of animal personality has potential benefit for conservation
      management. Due to logistics of robust behavioural evaluation in situ, the
      majority of studies on wild animals involve taking animals into captivity for
      testing, potentially compromising results. Three in situ tests for evaluation of
      boldness in San Joaquin kit fox (Vulpes macrotis mutica) were developed (ENOT:
      extended novel object test; RNOT: rapid novel object test; TH: trap/handling
      test). Each test successfully identified variation in boldness within its target
      age class(es). The TH test was suitable for use across all age classes. Tests
      were assessed for in situ suitability and for quantity/quality of data yielded.
      ENOT was rated as requiring high levels of time, cost and labour with greater
      likelihood of failure. However, it was rated highly for data quantity/quality.
      The TH test was rated as requiring little time, labour and cost, but yielding
      lower quality data. RNOT was rated in the middle. Each test had merit and could
      be adapted to suit project or species constraints. We recommend field-based
      evaluation of personality, reducing removal of animals from the wild and
      facilitating routine incorporation of personality assessment into conservation
      projects.

PMID- 29353955
TI  - Early arriving males wait longer for a mate than later arrivals: the case of a
      migratory monogamous passerine bird species.
AB  - Individuals that arrive earlier on the breeding grounds may obtain many
      advantages but they also have to spend time waiting for a mate. I studied the
      waiting times of male red-breasted flycatchers Ficedula parva, a small,
      migratory, sexually dichromatic passerine bird species under natural conditions
      (Bialowieza National Park, Poland) in relation to year, arrival time, age of male
      and morphological parameters. The length of waiting time was dependent on males'
      arrival time. The males which arrived later waited a shorter time for females
      than earlier arrivals. In some years older males spent more time waiting for
      mates than younger males, but in other years they waited for shorter times. A
      significant interaction between age of male and year was also observed. Despite
      the significantly earlier arrival of older males, the waiting time was not
      related to male age. The waiting time was also not related to body biometric
      parameters of the male. Despite waiting longer, early male red-breasted
      flycatchers have an advantage over later arrivals given this greater chance of
      mating.

PMID- 29353956
TI  - Diffusion in a tube of alternating diameter.
AB  - The paper deals with diffusion of a particle in a tube that consists of
      alternating wide and narrow sections. At sufficiently long times the particle
      motion can be coarse-grained and described as effective free-diffusion along the
      tube axis. In the coarse-grained description all the details of the tube geometry
      are packed into the effective diffusion coefficient of the particle. We derive a
      formula for the effective diffusion coefficient, which shows how it depends on
      the geometric parameters of the tube. To test the accuracy of this formula we
      compare its predictions with the values of the effective diffusion coefficient
      found in Brownian dynamics simulations. The comparison shows that the formula is
      applicable at arbitrary values of the length and radius of the narrow sections on
      condition that the radius of the wide sections does not exceed their length.

PMID- 29353958
TI  - Un-reduction in field theory.
AB  - The un-reduction procedure introduced previously in the context of classical
      mechanics is extended to covariant field theory. The new covariant un-reduction
      procedure is applied to the problem of shape matching of images which depend on
      more than one independent variable (for instance, time and an additional
      labelling parameter). Other possibilities are also explored: nonlinear [Formula:
      see text]-models and the hyperbolic flows of curves.

PMID- 29353957
TI  - Magnetic separation of algae genetically modified for increased intracellular
      iron uptake.
AB  - Algae were investigated in the past as a potential source of biofuel and other
      useful chemical derivatives. Magnetic separation of algae by iron oxide
      nanoparticle binding to cells has been proposed by others for dewatering of
      cellular mass prior to lipid extraction. We have investigated feasibility of
      magnetic separation based on the presence of natural iron stores in the cell,
      such as the ferritin in Auxenochlorella protothecoides (A. p.) strains. The A. p.
      cell constructs were tested for inserted genes and for increased intracellular
      iron concentration by inductively coupled plasma atomic absorption (ICP-AA). They
      were grown in Sueoka's modified high salt media with added vitamin B1 and
      increasing concentration of soluble iron compound (FeCl3 EDTA, from 1* to 8*
      compared to baseline). The cell magnetic separation conditions were tested using
      a thin rectangular flow channel pressed against interpolar gaps of a permanent
      magnet forming a separation system of a well-defined fluid flow and magnetic
      fringing field geometry (up to 2.2 T and 1,000 T/m) dubbed "magnetic deposition
      microscopy", or MDM. The presence of magnetic cells in suspension was detected by
      formation of characteristic deposition bands at the edges of the magnet
      interpolar gaps, amenable to optical scanning and microscopic examination. The
      results demonstrated increasing cellular Fe uptake with increasing Fe
      concentration in the culture media in wild type strain and in selected
      genetically-modified constructs, leading to magnetic separation without magnetic
      particle binding. The throughput in this study is not sufficient for an
      economical scale harvest.

PMID- 29353959
TI  - PTSD in Long Term Care.

PMID- 29353960
TI  - Education and transition to work: evidence from Vietnam, Cambodia and Nepal.
AB  - Against the background of education expansion and economic transformations,
      little is known about how education shapes the transition to work in developing
      countries. Drawing on the cases of Vietnam, Cambodia and Nepal, this study
      examines the association between education and the timing and quality of
      transition to work. In Vietnam and Cambodia, school enrolment delays the
      transition to first paid employment, but upon leaving school, higher education
      attainment is associated with faster rate of transition. The education gradient
      is even stronger in probabilities and rates of transition to first stable, long
      term employment. In Nepal, school enrolment does not preclude transition to paid
      employment, and the relation between education attainment and transition to work
      varies significantly by gender.

PMID- 29353961
TI  - Adaptive Management of Urban Ecosystem Restoration: Learning from Restoration
      Managers in Rhode Island, U.S.A.
AB  - Urban aquatic restoration can be difficult to accomplish because of complications
      like pollutants, population density, infrastructure, and expense; however,
      restoration in urban settings has the potential to provide benefits to many
      people. The success of urban restoration projects-even those focused primarily on
      ecological targets-depends on community involvement and managers' understanding
      and consideration of community needs. However research on the social barriers to
      urban restoration and strategies managers use to overcome them is relatively
      rare. This work attempts to fill that gap. Building from interviews with
      restoration managers involved in urban aquatic restoration projects in Rhode
      Island, we contribute through an adaptive management approach: identifying and
      synthesizing the barriers for aquatic restoration projects in urban settings and
      strategies to overcome them. Ultimately, we suggest potential for double- and
      triple-loop learning by disentangling and critiquing the frames and policy/power
      structures that influence decision making in urban aquatic restoration.

PMID- 29353962
TI  - Children's Sensitivity to Cost and Reward in Decision Making Across Distinct
      Domains of Probability, Effort, and Delay.
AB  - Many behavioral paradigms used to study individuals' decision making tendencies
      do not capture the decision components that contribute to behavioral outcomes,
      such as differentiating decisions driven toward a reward from decisions driven
      away from a cost. This study tested a novel decision making task in a sample of
      403 children (age 9 years) enrolled in an ongoing longitudinal study. The task
      consisted of 3 blocks representing distinct cost domains (delay, probability,
      effort) wherein children were presented with a deck of cards, each of which
      consisted of a reward and a cost. Children elected whether to accept or skip the
      card at each trial. Reward-cost pairs were selected using an adaptive algorithm
      to strategically sample the decision space in the fewest number of trials. Using
      person-specific regression models, decision preferences were quantified for each
      cost domain with respect to general tolerance (intercept), as well as parameters
      estimating the effect of incremental increases in reward or cost on the
      probability of accepting a card. Results support the relative independence of
      decision making tendencies across cost domains, with moderate correlations
      observed between tolerance for delay and effort. Specific decision parameters
      showed unique associations with cognitive and behavioral measures including
      executive function, academic motivation, anxiety, and hyperactivity. Evidence
      indicates that sensitivity to reward is an important factor in incentivizing
      decisions to work harder or wait longer. Dissociating the relative contributions
      of reward and cost sensitivity in multiple domains may facilitate the
      identification of heterogeneity in sub-optimal decision making.

PMID- 29353963
TI  - Evidence for Opportunity Cost Neglect in the Poor.
AB  - People often neglect opportunity costs: They do not fully take into account
      forgone alternatives outside of a particular choice set. Several scholars have
      suggested that poor people should be more likely to spontaneously consider
      opportunity costs, because budget constraints should lead to an increased focus
      on trade-offs. We did not find support for this hypothesis in five high-powered
      experiments (total N = 2325). The experiments used different products (both
      material and experiential) with both high and low prices (from $8.50 to $249.99)
      and different methods of reminding participants of opportunity costs. High-income
      and low-income participants showed an equally strong decrease in willingness to
      buy when reminded of opportunity costs, implying that both the rich and the poor
      neglect opportunity costs.

PMID- 29353964
TI  - Efficient transformation in characteristics of cations supported-reduced graphene
      oxide nanocomposites for the destruction of trichloroethane.
AB  - Experiments were conducted to investigate the use of graphene-oxide supported
      metallic nanocomposites for improving the degradation of trichloroethane (TCA) by
      sodium percarbonate (SPC). Two methods of production, chemical reduction (CR) and
      solvo-thermal (ST), were tested for preparation of single (Fe) and binary (Fe-Cu)
      nanocomposites supported by reduced graphene oxide (rGO). A variety of analytical
      techniques including N2 adsorption Brunauer-Emmett-Teller (BET), x-ray
      diffraction (XRD), fourier-transfrom infrared spectroscopy (FTIR), and
      transmisison electron microscopy (TEM) were applied to characterize the
      physicochemical and microstructural properties of the synthesized nanocomposites.
      The characterization indicated that the CR method produced nanocomposites that
      comprised only mesoporous structure. Conversely, both micro and mesoporous
      structures were present for samples produced with the ST method. The synthesized
      single and bimetallic composites produced from the ST method showed higher
      surface areas, i.e. 93.6 m2/g and 119.2 m2/g as compared to the ones synthesized
      via the CR method, i.e. 13.8 m2/g and 38.0 m2/g respectively. The results of FTIR
      and XRD analyses confirmed that the ST method produced highly crystalline
      nanocomposites. SEM and TEM analysis validated that metallic particles with
      definite morphology well distributed on the surface of rGO. X-ray photoelectron
      spectroscopy (XPS) analysis confirmed the homogeneity nanocomposites and
      occurrence of variation in copper oxidation states during degradation process.
      EDS mapping validate the homogeneous distribution of Cu and Fe at reduced
      graphene oxide surface. The Fe-Cu/rGO (ST) activated SPC system effectively
      degraded TCA (92%) in 2.5 h at low nanocomposite dose compared to the Fe-Cu/rGO
      (CR) and only Fe, for which the maximum degradation efficiencies achieved were
      81% and 34%. In conclusion, excellent catalytic characteristics were observed for
      the ST-synthesized single and bimetallic (Fe/rGO, Fe-Cu/rGO) catalysts. These
      catalysts were successful in improving the degradation of TCA via activated SPC.

PMID- 29353966
TI  - Susceptibility of Faba Bean (Vicia faba L.) to Heat Stress During Floral
      Development and Anthesis.
AB  - Experiments were conducted over 2 years to quantify the response of faba bean
      (Vicia faba L.) to heat stress. Potted winter faba bean plants (cv. Wizard) were
      exposed to temperature treatments (18/10; 22/14; 26/18; 30/22; 34/26  degrees C
      day/night) for 5 days during floral development and anthesis. Developmental
      stages of all flowers were scored prior to stress, plants were grown in exclusion
      from insect pollinators to prevent pollen movement between flowers, and yield was
      harvested at an individual pod scale, enabling effects of heat stress to be
      investigated at a high resolution. Susceptibility to stress differed between
      floral stages; flowers were most affected during initial green-bud stages. Yield
      and pollen germination of flowers present before stress showed threshold
      relationships to stress, with lethal temperatures (t50) ~28  degrees C and ~32 
      degrees C, while whole plant yield showed a linear negative relationship to
      stress with high plasticity in yield allocation, such that yield lost at lower
      nodes was partially compensated at higher nodal positions. Faba bean has many
      beneficial attributes for sustainable modern cropping systems but these results
      suggest that yield will be limited by projected climate change, necessitating the
      development of heat tolerant cultivars, or improved resilience by other
      mechanisms such as earlier flowering times.

PMID- 29353965
TI  - Synthesis of iron-based metal-organic framework MIL-53 as an efficient catalyst
      to activate persulfate for the degradation of Orange G in aqueous solution.
AB  - A series of MIL-53(Fe) materials were synthesized using a solvothermal method
      under different temperature and time conditions and were used as catalysts to
      activate persulfate and degrade Orange G (OG). Influences of the above conditions
      on the crystal structure and catalytic behavior were investigated. Degradation of
      OG under different conditions was evaluated, and the possible activation
      mechanism was speculated. The results indicate that high synthesis temperature
      (larger than 170  degrees C) leads to poor crystallinity and low catalytic
      activity, while MIL-53(Fe) cannot fully develop at low temperature (100 or 120 
      degrees C). The extension of synthesis time from 5 h to 3 d can increase the
      crystallinity of the samples, but weakened the catalytic activity, which was
      caused by the reduction of BET surface area and the amount of Fe (II)
      coordinative unsaturated sites. Among all the samples, MIL-53(Fe)-A possesses the
      best crystal structure and catalytic activity. In optimal conditions, OG can be
      totally decolorized after degradation for 90 min, and a removal rate of 74% for
      COD was attained after 120 min. The initial solution pH had great influence on OG
      degradation, with the greatest removal in acidic pH environment. ESR spectra
      showed that sulfate radical (SO4- .), hydroxyl radical (OH.), persulfate radical
      (S2O8- .), and superoxide radical (O2.) exist in this system under acidic
      conditions. Furthermore, with the increase of pH, the relative amount of O2.
      increases while that of OH. and SO4- . decreases, resulting in a reduced
      oxidizing capacity of the system.

PMID- 29353967
TI  - Methods for estimating complier average causal effects for cost-effectiveness
      analysis.
AB  - In randomized controlled trials with treatment non-compliance, instrumental
      variable approaches are used to estimate complier average causal effects. We
      extend these approaches to cost-effectiveness analyses, where methods need to
      recognize the correlation between cost and health outcomes. We propose a Bayesian
      full likelihood approach, which jointly models the effects of random assignment
      on treatment received and the outcomes, and a three-stage least squares method,
      which acknowledges the correlation between the end points and the endogeneity of
      the treatment received. This investigation is motivated by the REFLUX study,
      which exemplifies the setting where compliance differs between the randomized
      controlled trial and routine practice. A simulation is used to compare the
      methods' performance. We find that failure to model the correlation between the
      outcomes and treatment received correctly can result in poor confidence interval
      coverage and biased estimates. By contrast, Bayesian full likelihood and three
      stage least squares methods provide unbiased estimates with good coverage.

PMID- 29353968
TI  - USING DIVERSE EXPERTISE TO ADVANCE CLIMATE CHANGE FISHERIES SCIENCE.
AB  - As climate change continues to impact New England's coastal ecosystems and their
      related fisheries, the need for measuring, projecting, interpreting, and applying
      those impacts for adaptive management is expanding. In New England, different
      types of formal and informal research efforts that involve collaboration between
      the fishing community and traditional university and government researchers
      continue to develop to address some of this need. To better understand the
      opportunities and challenges that these collaborative research efforts face, we
      conducted semi-structured interviews with 18 members of the fishing and research
      communities who are engaged in advancing New England climate change and fisheries
      science. Participants showed clear concern for the impacts of climate change on
      New England fisheries and about the insufficient availability of the necessary
      science to manage for those impacts. They also noted a number of challenges in
      collaborative research, including poor communication and a lack of trust among
      fishers, researchers, and decision makers, as well as a lack of perceived
      credibility for research coming out of the fishing community. We identify a
      number of opportunities for improving collaboration and communication among these
      groups, which could build upon the identified value of existing collaborations.

PMID- 29353969
TI  - Incidence and mortality of cervical cancer in China, 2013.
AB  - Objective: Estimating the incidence and mortality rate of cervical cancer became
      necessary to establish prevention measures and healthy policies. The aim of this
      study was to estimate the updated incidence and mortality rate of cervical cancer
      in 2013 in China. Methods: According to the evaluation criteria developed by the
      National Central Cancer Registry of China, the data submitted from 255 cancer
      registries met the required standards in 2013. Cervical cancer cases were
      retrieved from the national database and combined with the 2013 national
      population data. The age-standardized incidence and mortality rates were based on
      the demographic structure of the national census 2000 and Segi's world
      population. Results: In 2013, the estimated number of new cases and deaths from
      cervical cancer were 100,700 and 26,400, respectively. The crude incidence of
      cervical cancer was 15.17/100,000. The age-standardized incidence rates based on
      the Chinese standard population (ASIRC) and the world standard population (ASIRW)
      were 11.30/100,000 and 10.30/100,000, respectively. The incidence of cervical
      cancer in urban areas was 15.62/100,000 and the ASIRC was 11.12/100,000. The
      incidence of cervical cancer in rural areas was 14.65/100,000 and the ASIRC was
      11.47/100,000. The mortality rate of cervical cancer was 3.98/100,000. The age
      standardized mortality rates based on the Chinese (ASMRC) and world standard
      populations (ASMRW) were 2.76/100,000 and 2.62/100,000, respectively. The
      mortality rate of cervical cancer in urban areas was 3.85/100,000 and in rural
      areas was 4.14/100,000. Cervical cancer incidence and mortality increased with
      age. Urban areas had a higher incidence of cervical cancer and lower mortality
      rates when compared with rural areas. Conclusions: Dynamic monitoring of cervical
      cancer incidence and mortality is the fundamental work of cervical cancer
      prevention and control. Cervical cancer is a serious issue in women's health, and
      prevention strategies need to be enhanced, such as human papilloma virus (HPV)
      vaccination and screening programs.

PMID- 29353970
TI  - Trends of incidence rate and age at diagnosis for cervical cancer in China, from
      2000 to 2014.
AB  - Objective: To analyze the trends of incidence rate and age at diagnosis for
      cervical cancer incidence in China using population-based cancer registration
      data from 2000 to 2014. Methods: Data were from National Central Cancer Registry
      of China. Crude incidence rates (CIRs), age-specific incidence rate, age
      standardized incidence rates (ASIRs), age percentage distribution, standardized
      age percentage distribution, mean age at diagnosis and standardized mean age at
      diagnosis for cervical cancer in all areas of China, urban China and rural China
      were calculated separately. The world Segi's population was applied to remove the
      age structure influence. Joinpoint regression was performed to obtain average
      annual percent change (AAPC) and age-period-cohort analysis was used to examine
      the incidence trends. Results: CIRs and ASIRs for cervical cancer increased in
      China from 2000 to 2014. The AAPC of ASIRs in China was at 9.2% [95% confidence
      interval (95% CI): 7.0%-11.5%, P<0.05], and the AAPC in rural areas was
      relatively high. The age-specific incidence rate in groups aged 0-69 years have
      significantly increased over time. Groups aged 40-69 years showed the highest
      incidence risk, and the annual percent changes (APCs) of incidence rate in groups
      aged 40-59 years in urban China and groups aged 0-49 years in rural China were
      more than 10%. For each age group, the urban-to-rural incidence rate ratios
      (IRRs) got close to 1 over time. There were clear birth cohort effects in
      successive generations born from 1940 to 1970 in China. In rural China, the
      standardized mean age at diagnosis had significantly declined by 5.18 years. In
      China, the main peak and secondary peak of standardized age percentages appeared
      in the groups aged 45-49 and 40-44 years, respectively. In rural China, the main
      peak of standardized age percentage moved from the group aged 55-59 years to the
      group aged 45-49 years, and the standardized age percentages of groups aged 25-34
      years also increased. In China, the standardized age percentages has
      significantly increased in groups aged 35-64 and 30-64 years over time, and
      accounted for about 80% and 85% in 2014, respectively. Conclusions: The cervical
      cancer incidence increased in China and the gap of incidence between urban and
      rural China was narrowed. The trends of increasing cervical cancer incidence
      among younger women existed in China, especially in rural China. A more
      appropriate screening, vaccination and health education strategies should be
      established.

PMID- 29353971
TI  - Trends in geographical disparities for cervical cancer mortality in China from
      1973 to 2013: a subnational spatio-temporal study.
AB  - Objective: This study was designed to explore the time trends in geographical
      variations of cervical cancer mortality in mainland China over the period 1973 to
      2013, to provide subnational spatio-temporal patterns for targeted promotion of
      human papillomavirus vaccine in China. Methods: Data were extracted from three
      national retrospective death surveys and cancer registry. The rate ratio (RR) was
      estimated for the aggregated data for seven geographical regions using
      generalized linear models to evaluate time trends in geographical disparities of
      cervical cancer mortality. Results: There was a significant decrease in cervical
      cancer mortality in China from 1973-1975 to 2004-2005, but leveled off thereafter
      to 2011-2013. Compared to the period 1973-1975 the RR for the three last time
      periods were 0.33 [95% confidence interval (95% CI): 0.30-0.37] for 1990-1992,
      0.21 (95% CI: 0.19-0.24) for 2004-2005 and 0.24 (95% CI: 0.22-0.26) for 2011
      2013. Females living in the Northwest China and Central China have a high risk of
      mortality from cervical cancer compared to the nationwide, with the RR being 2.09
      (95% CI: 1.83-2.38) and 1.26 (95% CI: 1.11-1.44) respectively, while the RRs for
      South China, Northeast China and Southwest China were below 1.00, indicating the
      lower death risk. Despite the mortality rate had increased slightly from 2004 to
      2013, there was an encouraging sign that the geographical disparities in cervical
      cancer mortality had gradually narrowed over time across China. Conclusions:
      Although cervical cancer mortality in China has reduced to very low levels, the
      high risk of cervical cancer in Northwest China and Central China is still
      noteworthy. Public health policies including the promotion of vaccine should be
      targeted to further reduction of geographical disparities in cervical cancer
      mortality.

PMID- 29353972
TI  - Accuracy of triage strategies for human papillomavirus DNA-positive women in low
      resource settings: A cross-sectional study in China.
AB  - Objective: CareHPV is a human papillomavirus (HPV) DNA test for low-resource
      settings (LRS). This study assesses optimum triage strategies for careHPV
      positive women in LRS. Methods: A total of 2,530 Chinese women were concurrently
      screened for cervical cancer with visual inspection with acetic acid (VIA),
      liquid-based cytology and HPV testing by physician- and self-collected careHPV,
      and physician-collected Hybrid Capture 2 (HC2). Screen-positive women were
      referred to colposcopy with biopsy and endocervical curettage as necessary. HPV
      positivity was defined as >=1.0 relative light units/cutoff (RLU/CO) for both
      careHPV and HC2. Primary physician-HC2, physician-careHPV and self-careHPV and in
      sequential screening with cytology, VIA, or increased HPV test-positivity
      performance, stratified by age, were assessed for cervical intraepithelial
      neoplasia (CIN) grade 2/3 or worse (CIN2/3+) detection. Results: The
      sensitivities and specificities of primary HPV testing for CIN2+ were: 83.8%,
      88.1% for physician-careHPV; 72.1%, 88.2% for self-careHPV; and 97.1%, 86.0% for
      HC2. Physician-careHPV test-positive women with VIA triage had a sensitivity of
      30.9% for CIN2+ versus 80.9% with cytology triage. Self-careHPV test-positive
      women with VIA triage was 26.5% versus 66.2% with cytology triage. The
      sensitivity of HC2 test-positive women with VIA triage was 38.2% versus 92.6%
      with cytology triage. The sensitivity of physician-careHPV testing for CIN2+
      decreased from 83.8% at >=1.0 RLU/CO to 72.1% at >=10.00 RLU/CO, while the
      sensitivity of self-careHPV testing decreased from 72.1% at >=1.0 RLU/CO to 32.4%
      at >=10.00 RLU/CO; similar trends were seen with age-stratification. Conclusions:
      VIA and cytology triage improved specificity for CIN2/3 than no triage.
      Sensitivity with VIA triage was unsuitable for a mass-screening program. VIA
      provider training might improve this strategy. Cytology triage could be feasible
      where a high-quality cytology program exists. Triage of HPV test-positive women
      by increased test positivity cutoff adds another LRS triage option.

PMID- 29353973
TI  - Prognostic evaluation of postoperative adjuvant therapy for operable cervical
      cancer: 10 years' experience of National Cancer Center in China.
AB  - Objective: The aim of this study was to investigate the prognostic factors and to
      evaluate the impact of adjuvant therapy on clinical outcome for early-stage
      cervical cancer. Methods: The clinical-pathological data of all 1,335 patients
      with the International Federation of Gynecology and Obstetrics (FIGO) Ib-IIa
      cervical cancer treated with primary radical surgery at the Chinese National
      Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The
      median follow-up was 70 months. Results: Of all the patients, 61.6% of the cases
      received adjuvant therapy, with 5-year disease-free survival (DFS) of 92.1% and 5
      year overall survival (OS) of 95.0%. In multivariate analysis, differentiation of
      G3 (P<0.05), lymph node metastasis (LNM, P<0.05) and lymphovascular space
      invasion (LVSI, P<0.05) were independent predictors for OS, while LNM (P<0.05),
      deep stroma invasion (DSI, P<0.05) and LVSI (P<0.05) were independent factors for
      DFS. The samples were stratified by histologic type, and cervical squamous cell
      carcinoma (SCC) was found to share the same independent factors except for
      differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamous
      carcinoma (AC/ASC), differentiation was the independent predictor of OS (P<0.05);
      and LVSI of DFS (P<0.05). Of 236 patients with high-risk factors, there was no
      significant difference in survival between concurrent chemoradiotherapy (CCRT,
      n=195), radiotherapy (RT, n=24), and chemotherapy (CT, n=17). Among the 190
      patients with LNM who underwent CCRT, 124 cases showed improved DFS after
      sequential CT (P=0.118), with a recurrence rate decrease of 14%, though the
      difference was not statistically significant. Patients with single intermediate
      risk factors like DSI or LVSI were found to partially benefit from adjuvant
      therapy, but the difference was not statistically significant. Conclusions: LNM,
      LVSI, DSI and differentiation were found to be independent prognostic factors for
      operable cervical cancer. Aggressive postoperative adjuvant therapy based on
      single risk factors in Chinese National Cancer Center could benefit survival.
      CCRT+CT outperformed CCRT in high-risk patients. For patients with single non
      high-risk factor, the role of adjuvant therapy needs to be further discussed.

PMID- 29353975
TI  - Debulking surgery and hyperthermic intrathoracic chemotherapy (HITHOC) for lung
      cancer.

PMID- 29353974
TI  - Outcome and prognostic factors in 110 consecutive patients with primary uterine
      leiomyosarcoma: A Rare Cancer Network study.
AB  - Objective: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal
      treatment is controversial. We aimed to assess the outcome and prognostic factors
      in a multicenter population of women treated for primary ULMS. Methods: We
      retrospectively collected data of 110 women treated in 19 institutions of the
      Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report
      confirming the diagnosis of ULMS, aged 18-80 years, complete International
      Federation of Gynecology and Obstetrics (FIGO) stage information, complete
      information on treatment, and a minimum follow-up of 6 months. Local control (LC)
      and locoregional control (LRC), overall survival (OS) and disease-free survival
      (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was
      implemented using the log rank test, and multivariate analysis using the Cox
      model. Results: All patients underwent surgery. Seventy-five patients (68%)
      received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%).
      Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58
      (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and
      LRC rates were 88% and 72%, respectively. On multivariate analysis, independent
      favorable prognostic factors were younger age, FIGO stage I, small tumor size,
      previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was
      the only favorable factor influencing LRC. Adjuvant local or systemic treatments
      did not improve the outcomes. Eight patients treated with RT presented a grade 3
      acute toxicity, and only one patient with grade 3 late toxicity. Conclusions: In
      this large population of primary ULMS patients, we found good results in terms of
      LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of
      distant metastases. An early diagnosis seemed to improve the prognosis of the
      patients. Adjuvant local or systemic treatments, or more aggressive surgical
      procedures such as the Wertheim procedure, did not seem to impact the outcome.

PMID- 29353976
TI  - Targeted therapy for leptomeningeal metastases in non-small cell lung cancer -
      Changing treatment paradigms.
AB  - Leptomeningeal metastasis is an uncommon but serious complication in patients
      with advanced cancers. Leptomeningeal metastasis is diagnosed in approximately 5%
      of the patients, most commonly among patients with cancers of breast and lung,
      melanoma, and gastrointestinal malignancies. Treatment goal is to improve
      survival and quality of the patients. Use of targeted therapies and immunotherapy
      has led to improved survival of patients with non-small cell lung cancer (NSCLC).
      In this article, we review emerging data on use of mutation-specific agents and
      immunotherapy in the treatment of leptomeningeal metastasis among patients with
      NSCLC.

PMID- 29353977
TI  - Uncommon EGFR mutations in a cohort of Chinese NSCLC patients and outcomes of
      first-line EGFR-TKIs and platinum-based chemotherapy.
AB  - Objective: Data on the clinical activity of epidermal growth factor receptor
      (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung
      cancer (NSCLC) and uncommon EGFR mutations remain insufficient. This study aimed
      to investigate the effect of first-line EGFR-TKIs or platinum-based chemotherapy
      in NSCLC patients with uncommon EGFR mutations. Methods: We retrospectively
      enrolled 504 patients with EGFR-mutant NSCLC. The clinical characteristics and
      treatment outcomes were collected and compared between patients with common and
      uncommon EGFR-mutant NSCLC. Results: Seventy patients (13.9%) harboring uncommon
      EGFR mutations were included. Thirty of these patients received EGFR-TKIs and 40
      received platinum-based chemotherapy as first-line therapy. The objective
      response rate (ORR) and median progression-free survival (mPFS) of patients
      treated with TKIs in the uncommon mutation group was significantly inferior to
      that in the common mutation group (ORR: 23.3% vs. 51.8%, P=0.003; mPFS: 7.1 vs.
      10.9 months, P<0.001). In the uncommon group, mPFS was similar between first-line
      EGFR-TKIs treatment and platinum-based chemotherapy (7.1vs. 6.1 months, P=0.893).
      In patients with EGFR G719X or L861Q mutations, the mPFS was longer in the first
      line EGFR-TKIs treatment group than in the chemotherapy group, but the difference
      was not statistically significant (G719X: 8.2 vs. 5.8 months, P=0.061; L861Q: 7.6
      vs. 4.1 months, P=0.872). Multivariate analyses identified adenocarcinoma
      (P=0.003) as the independent predictive factor for PFS in patients with uncommon
      EGFR mutations who were treated with first-line EGFR-TKIs. Conclusions: The
      current study demonstrated that the effect of first-line EGFR-TKIs was similar to
      that of platinum-based chemotherapy in patients with uncommon EGFR-mutant NSCLC.
      Adenocarcinoma was the independent predictive factor for PFS in uncommon EGFR
      mutant NSCLC patients treated with first-line EGFR-TKIs.

PMID- 29353978
TI  - Survival difference between EGFR Del19 and L858R mutant advanced non-small cell
      lung cancer patients receiving gefitinib: a propensity score matching analysis.
AB  - Objective: Although superior clinical benefits of epidermal growth factor
      receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced
      non-small-cell lung cancer (NSCLC) had been reported, the survival difference
      between exon 19 deletion (Del19) and exon 21 Leu858Arg substitution (L858R)
      remains controversial. The purpose of this study is to investigate the
      differences in progression-free survival (PFS) and overall survival (OS) between
      different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib.
      Methods: There were 204 advanced NSCLC patients with EGFR mutations treated with
      gefitinib were enrolled in this retrospective cohort study. Patients were divided
      into the EGFR Del19 group and the L858R mutated group according to their mutant
      subtype. Propensity score matching (PSM) was conducted by using a nearest
      neighbor algorithm (1:1) to adjust for demographical and clinical covariates.
      Survival curves were constructed with the Kaplan-Meier method and compared by
      using the log-rank test. Results: The PFS in Del19 group was similar to that in
      the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2
      months, P=0.155]. No differences were detected in OS between the L858R and the
      Del19 group (before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1
      months, P=0.339). The Del19 group was significantly younger compared with the
      L858R mutation group in age (P=0.015). Conclusions: No significant difference was
      found in the PFS or OS between the Del19 and L858R mutant NSCLC patients
      receiving gefitinib. The age gap might contribute to the survival differences
      between Del19 and L858R groups. PSM is of important value to the elimination of
      potential bias.

PMID- 29353979
TI  - Prognostic value of pre- and post-transplantation 18F-fluorodeoxyglucose positron
      emission tomography results in non-Hodgkin lymphoma patients receiving autologous
      stem cell transplantation.
AB  - Objective: High-dose chemotherapy (HDC) followed by autologous stem cell
      transplantation (ASCT) is the standard of care in the upfront or
      relapsed/refractory setting in some patients with non-Hodgkin lymphoma (NHL).
      However, a proportion of patients do not respond to ASCT. 18F-fluorodeoxyglucose
      (FDG) positron emission tomography (PET)/computed tomography (CT) has been widely
      used for staging, response evaluation, and prognosis prediction. Here, we
      investigated the prognostic role of PET/CT in NHL patients before and after ASCT.
      Methods: A retrospective study was conducted at Peking University Cancer
      Hospital. All NHL patients who underwent ASCT between March 2010 and July 2016
      were identified. Patients who had PET/CT scan before and after ASCT were
      included. Deauville criteria (5-point scale) were used to interpret PET scans.
      Univariate and multivariate survival analyses were performed using Cox
      regression. The predictive value of PET scanning was estimated by comparing the
      area under the receiver operating characteristic (ROC) curve. Results: In total,
      79 patients were enrolled in this study. In univariate analysis, pre- and post
      ASCT PET result was identified as prognostic factors for 3-year progression-free
      survival (PFS) and overall survival (OS). Patients with negative pre-ASCT PET
      result demonstrated significantly better PFS (84.2% vs. 54.2%) and OS (89.2% vs.
      63.6%) than patients with positive pre-ASCT PET result. PFS (91.6% vs. 25.3%) and
      OS (96.5% vs. 36.8%) were also significantly different between patients with
      negative and positive post-ASCT PET result. Multivariate analysis also showed a
      significant association between survival and post-ASCT PET result. ROC analysis
      revealed that the predictive value of post-ASCT PET result was superior to that
      of pre-ASCT PET result alone. Combined pre- and post-ASCT PET result is better
      for predicting outcomes in patients with NHL receiving transplantation. Deauville
      criteria score >3 was identified as the best cutoff value for post-ASCT PET.
      Conclusions: Post-ASCT PET result was more important than pre-ASCT PET result in
      predicting outcomes for NHL patients who underwent ASCT. The prognostic
      significance can be improved when combining pre-ASCT PET result with post-ASCT
      PET result. Deauville criteria can be used for interpreting PET scans in this
      scenario.

PMID- 29353980
TI  - HOXC10 up-regulation promotes gastric cancer cell proliferation and metastasis
      through MAPK pathway.
AB  - Objective: As an important regulator of embryonic morphogenesis, homeodomain
      containing gene 10 (HOXC10) has been found to promote progression of human
      cancers and its expression indicates poor survival outcome. However, very few
      studies are available on the role of HOXC10 in gastric carcinoma. Therefore, the
      aim of this study was to determine the role of HOXC10 in gastric cancer and the
      potential mechanism underlying its function for cancer biology. Methods: A
      primary gastric cancer mouse model was obtained via intra-gastric wall injection
      of gastric cancer cells and was used to evaluate the function of HOXC10 during
      gastric cancer progression in vivo. Immunohistochemistry was performed to
      visualize and measure HOXC10 protein expression in gastric cancer tissue. Cells
      were transfected with plasmids to increase the expression of HOXC10, and siRNA
      transfection was performed to suppress HOXC10 expression. Reverse transcription
      polymerase chain reaction (RT-PCR) and western blotting were utilized to measure
      mRNA and protein expression, respectively. Proliferation, migration, and invasion
      were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay, wound healing assay, and matrigel invasion assay in vitro,
      respectively. Results: HOXC10 expression was significantly increased in gastric
      cancer tissues compared to matched normal tissues. HOXC10 up-regulation
      significantly increased tumor volumes in nude mice. Plasmid transfection
      significantly increased HOXC10 protein and mRNA expressions and effectively
      promoted cell proliferation. Moreover, HOXC10 up-regulation significantly
      promoted migration and invasion of gastric cancer cells. Mechanistic
      investigation showed that HOXC10 up-regulation significantly increased mRNA and
      protein expression of mitogen-activated protein kinase (MAPK) signaling related
      genes, including c-myc, c-jun and p53, while also modulating the phosphorylation
      of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and
      P38 but not their total protein levels. Conclusions: This study demonstrated the
      tight link between HOXC10 and gastric cancer cell proliferation and metastasis
      via involvement of the MAPK pathway.

PMID- 29353982
TI  - Remarkably different results between two studies from North America on genomic
      mutations and sensitivity to DNA demethylating agents for myelodysplastic
      syndromes.

PMID- 29353981
TI  - Retrospective analysis of interventional treatment of hepatic metastasis from
      gastroenteropancreatic neuroendocrine tumors.
AB  - Objective: To analyze the angiography appearance of liver metastases from
      gastroenteropancreatic neuroendocrine tumors (GEP-NETs), and evaluate the
      clinical efficacy and prognostic factors of interventional treatment for hepatic
      metastases. Methods: Fifty GEP-NETs patients with hepatic metastases were treated
      from January 2012 to December 2016, and received transarterial embolization (TAE)
      in the hepatic tumor or hepatic arterial infusion chemotherapy (HAIC). All
      patients received 179 times of the intervention therapy in total. Results: Blood
      supplies were identified in the 50 cases with angiography, which showed that 35
      cases had abundant vessels, while 15 cases had poor blood supply. Twenty-two
      cases were found either collateral blood supply, or portal vein invasion or
      arterial-portal vein fistula. The best curative efficacy was complete remission
      (CR) in 4 cases, partial remission (PR) in 28 cases and stable disease (SD) in 18
      cases during the process of treatment. The angiography (P=0.047) and the
      frequency of intervention (P=0.037) showed significantly statistical difference
      with Kaplan-Meier analysis. The Cox analysis showed that more than 3 times of
      interventional therapy was an independent prognostic factor. Conclusions:
      Interventional treatment is safe and effective for GEP-NETs, and is beneficial to
      patients with main hepatic metastases after endocrine therapy.

PMID- 29353983
TI  - Neuronal nitric oxide synthase in the lower reproductive tract of female
      Drosophila.

PMID- 29353984
TI  - Femtosecond Laser Eyewear Protection: Measurements and Precautions.
AB  - Ultrafast laser systems are becoming more widespread throughout the research and
      industrial communities yet eye protection for these high power, bright pulsed
      sources still require scrupulous characterization and testing before use.
      Femtosecond lasers, with pulses naturally possessing broad-bandwidth and high
      average power with variable repetition rate, can exhibit spectral side-bands and
      subtly changing center wavelengths, which may unknowingly affect eyewear safety
      protection. Pulse spectral characterization and power diagnostics are presented
      for a 80 MHz, Ti+3:Sapphire, ~ 800 nm, ~40 femtosecond oscillator system. Power
      and spectral transmission for 22 test samples are measured to determine whether
      they fall within manufacturer specifications.

PMID- 29353986
TI  - The Influence of Client Risks and Treatment Engagement on Recidivism.
AB  - The current study modeled 12 month post-release re-arrest (recidivism) in terms
      of pretreatment risk factors (i.e., criminal history, criminal thinking,) and
      during-treatment engagement in a sample of 653 subjects admitted to four prison
      based substance treatment programs. Structural Equation Modeling was used to test
      during-treatment engagement as a mediator variable in explaining the relationship
      between the pretreatment risk factors and recidivism. Results indicated that (1)
      a long history of criminal conduct correlated with criminal thinking, which in
      turn had a significantly negative relationship with engagement in treatment; (2)
      the level of criminal involvement had a significant relationship with re-arrest,
      whereas the level of criminal thinking did not influence being re-arrested
      directly; (3) the relationship between criminal history and re-arrest was
      partially mediated by criminal thinking and treatment engagement, whereas the
      relationship between criminal thinking and re-arrest was fully mediated by
      treatment engagement. The findings suggest that it is important to design
      interventions targeting criminal thinking and monitor treatment engagement as an
      indicator of treatment performance. Clinical implications also include the
      importance of facilitating treatment engagement and the utility of conducting
      prognostic assessment to inform treatment.

PMID- 29353985
TI  - Dietary Effects on Cognition and Pilots' Flight Performance.
AB  - The purpose of this study was to investigate the effects of diet on cognition and
      flight performance of 45 pilots. Based on a theory of self-care, this clinical
      study used a repeated-measure, counterbalanced crossover design. Pilots were
      randomly rotated through 4-day high-carbohydrate, high-protein, high-fat, and
      control diets. Cognitive flight performance was evaluated using a GAT-2 full
      motion flight simulator. The Sternberg short-term memory test and Vandenberg's
      mental rotation test were used to validate cognitive flight test results. Pilots
      consuming a high-protein diet had significantly poorer (p < .05) overall flight
      performance scores than pilots consuming high-fat and high-carbohydrate diets.

PMID- 29353988
TI  - An individualized super-Gaussian single microphone Speech Enhancement for hearing
      aid users with smartphone as an assistive device.
AB  - In this letter, we derive a new super Gaussian Joint Maximum a Posteriori
      (SGJMAP) based single microphone speech enhancement gain function. The developed
      Speech Enhancement method is implemented on a smartphone, and this arrangement
      functions as an assistive device to hearing aids. We introduce a "tradeoff"
      parameter in the derived gain function that allows the smartphone user to
      customize their listening preference, by controlling the amount of noise
      suppression and speech distortion in real-time based on their level of hearing
      comfort perceived in noisy real world acoustic environment. Objective quality and
      intelligibility measures show the effectiveness of the proposed method in
      comparison to benchmark techniques considered in this paper. Subjective results
      reflect the usefulness of the developed Speech Enhancement application in real
      world noisy conditions at signal to noise ratio levels of -5 dB, 0 dB and 5 dB.

PMID- 29353987
TI  - Acoustical Method of Whole-Body Hydration Status Monitoring.
AB  - An acoustical handheld hydration monitor (HM) for assessing the water balance of
      the human body was developed. Dehydration is a critical public health problem.
      Many elderly over age of 65 are particularly vulnerable as are infants and young
      children. Given that dehydration is both preventable and reversible, the need for
      an easy-to-perform method for the detection of water imbalance is of the utmost
      clinical importance. The HM is based on an experimental fact that ultrasound
      velocity in muscle is a linear function of water content and can be referenced to
      the hydration status of the body. Studies on the validity of HM for the
      assessment of whole-body hydration status were conducted in the Appalachian State
      University, USA, on healthy young adults and on elderly subjects residing at an
      assisted living facility. The HM was able to track changes in total body water
      during periods of acute dehydration and rehydration in athletes and day-to-day
      and diurnal variability of hydration in elderly. Results of human studies
      indicate that HM has a potential to become an efficient tool for detecting
      abnormal changes in the body hydration status.

PMID- 29353989
TI  - Process Safety Assessment of the Iron-Catalyzed Direct Olefin Diazidation for the
      Expedient Synthesis of Vicinal Primary Diamines.
AB  - We report herein a process safety assessment of the iron-catalyzed direct olefin
      diazidation for the preparation of a broad range of synthetically valuable
      vicinal primary diamines. Differential scanning calorimetry analysis of the
      corresponding reagents, intermediates, and a list of representative
      diazide/diaminium salt products revealed that all of them are thermal stable at
      the reaction temperature. The drop weight test of the diazides suggested that
      they are moderately impact-sensitive. Guided by this assessment, an optimized
      olefin diazidation/diamination procedure has been developed which allows for the
      gram-scale diaminium salt synthesis without purification of the diazide
      intermediate.

PMID- 29353990
TI  - Fabrication of An Inexpensive but Effective Colonoscopic Simulator.
AB  - Because of increasing requirements for simulator training before actual clinical
      endoscopies, the demand for realistic, inexpensive endoscopic simulators is
      increasing. We describe the steps involved in the design and fabrication of an
      effective and realistic mechanical colonoscopic simulator.

PMID- 29353991
TI  - Trends in Austrian Resource Efficiency: An Exergy and Useful Work Analysis in
      Comparison to Material Use, CO2 Emissions, and Land Use.
AB  - In the past few years, resource use and resource efficiency have been implemented
      in the European Union (EU) environmental policy programs as well as international
      sustainable development programs. In their programs, the EU focuses on four
      resource types that should be addressed: materials, energy (or carbon dioxide
      [CO2] emissions), water, and land. In this article, we first discuss different
      perspectives on energy use and present the results of a long-term exergy and
      useful work analysis of the Austrian economy for the period 1900-2012, using the
      methodology developed by Ayres and Warr. Second, we discuss Austrian resource
      efficiency by comparing the presented exergy and useful work data with material
      use, CO2 emissions, and land-use data taken from statistical sources. This
      comparison provides, for the first time, a long-term analysis of Austrian
      resource efficiency based on a broad understanding thereof and evaluates Austrian
      development in relation to EU and Austrian policy targets.

PMID- 29353993
TI  - Announcement of New Deputy Editor.

PMID- 29353994
TI  - Imaging Features of Inflammatory Breast Disorders: A Pictorial Essay.
AB  - Inflammatory breast disorders include a wide array of underlying causes, ranging
      from common benign infection, non-infectious inflammation and inflammation
      resulting from underlying breast malignancy. Because it is at times difficult to
      distinguish mastitis and breast cancer based on clinical features, awareness of
      detailed imaging features may be helpful for better management of inflammatory
      breast disorders. Therefore, this pictorial essay intends to demonstrate
      radiologic findings of a variety of inflammatory breast disorders, using selected
      cases with mammography, ultrasound and magnetic resonance images.

PMID- 29353995
TI  - Carotid Plaque Stiffness Measured with Supersonic Shear Imaging and Its
      Correlation with Serum Homocysteine Level in Ischemic Stroke Patients.
AB  - Objective: To ascertain the feasibility of using shear wave velocity (SWV) in
      assessing the stiffness of carotid plaque by supersonic shear imaging (SSI) and
      explore preliminary clinical value for such evaluation. Materials and Methods:
      Supersonic shear imaging was performed in 142 patients with ischemic stroke,
      including 76 males and 66 females with mean age of 66 years (range, 45-80 years).
      The maximum, minimum, and mean values of SWV were measured for 129 carotid
      plaques. SWVs were compared between echolucent and echogenic plaques.
      Correlations between SWVs and serum homocysteine levels were investigated. Based
      on neurological symptom, the surrogate marker of vulnerable plaque (VP), binary
      logistic regression was performed and area under curve (AUC) of homocysteine only
      and homocysteine combing SWVmean was calculated respectively. Results: Echogenic
      plaques (n = 51) had higher SWVs than echolucent ones (n = 78) (SWVmin 3.91 [3.24
      4.17] m/s vs. 1.51 [1.04-1.94] m/s; SWVmean, 4.29 [3.98-4.57] m/s vs. 2.09 [1.69
      2.41] m/s; SWVmax, 4.67 [4.33-4.86] m/s vs. 2.62 [2.32-3.31] m/s all p values <
      0.01). Pearson correlation analysis showed that stiffness of plaques was
      negatively correlated with homocysteine level. R values for SWVmin, SWVmean, and
      SWVmax were -0.205, -0.213, and -0.199, respectively. Binary logistic regression
      analysis showed that sex (p = 0.008), low-density lipoprotein (p = 0.015),
      triglycerides (p = 0.011), SWVmean (p = 0.004), and hyper-homocysteinemia (p =
      0.010) were significantly associated with symptomatic ischemic stroke. Receiver
      operating characteristic curves revealed that SWVmean combing serum homocysteine
      level (AUC = 0.67) presented better diagnostic value than serum homocysteine only
      (AUC = 0.60) for symptomatic ischemic stroke. Conclusion: Supersonic shear
      imaging could be used to quantitatively evaluate stiffness of both echolucent and
      echogenic carotid plaques. More importantly, SWVs of plaques were not only
      correlated to serum homocysteine level, but also associated with symptomatic
      ischemic stroke, suggesting that SSI might be useful for understanding more about
      VP.

PMID- 29353996
TI  - Comparison of Chest Pain Protocols for Electrocardiography-Gated Dual-Source
      Cardiothoracic CT in Children and Adults: The Effect of Tube Current Saturation
      on Radiation Dose Reduction.
AB  - Objective: To compare radiation doses between conventional and chest pain
      protocols using dual-source retrospectively electrocardiography (ECG)-gated
      cardiothoracic computed tomography (CT) in children and adults and assess the
      effect of tube current saturation on radiation dose reduction. Materials and
      Methods: This study included 104 patients (16.6 +/- 7.7 years, range 5-48 years)
      that were divided into two groups: those with and those without tube current
      saturation. The estimated radiation doses of retrospectively ECG-gated spiral
      cardiothoracic CT were compared between conventional, uniphasic, and biphasic
      chest pain protocols acquired with the same imaging parameters in the same
      patients by using paired t tests. Dose reduction percentages, patient ages,
      volume CT dose index values, and tube current time products per rotation were
      compared between the two groups by using unpaired t tests. A p value < 0.05 was
      considered significant. Results: The volume CT dose index values of the biphasic
      chest pain protocol (10.8 +/- 3.9 mGy) were significantly lower than those of the
      conventional protocol (12.2 +/- 4.7 mGy, p < 0.001) and those of the uniphasic
      chest pain protocol (12.9 +/- 4.9 mGy, p < 0.001). The dose-saving effect of
      biphasic chest pain protocol was significantly less with a saturated tube current
      (4.5 +/- 10.2%) than with unsaturated tube current method (14.8 +/- 11.5%, p <
      0.001). In 76 patients using 100 kVp, patient age showed no significant
      differences between the groups with and without tube current saturation in all
      protocols (p > 0.05); the groups with tube current saturation showed
      significantly higher volume CT dose index values (p < 0.01) and tube current time
      product per rotation (p < 0.001) than the groups without tube current saturation
      in all protocols. Conclusion: The radiation dose of dual-source retrospectively
      ECG-gated spiral cardiothoracic CT can be reduced by approximately 15% by using
      the biphasic chest pain protocol instead of the conventional protocol in children
      and adults if radiation dose parameters are further optimized to avoid tube
      current saturation.

PMID- 29353997
TI  - Left Gastric Vein Visualization with Hepatopetal Flow Information in Healthy
      Subjects Using Non-Contrast-Enhanced Magnetic Resonance Angiography with Balanced
      Steady-State Free-Precession Sequence and Time-Spatial Labeling Inversion Pulse.
AB  - Objective: To selectively visualize the left gastric vein (LGV) with hepatopetal
      flow information by non-contrast-enhanced magnetic resonance angiography under a
      hypothesis that change in the LGV flow direction can predict the development of
      esophageal varices; and to optimize the acquisition protocol in healthy subjects.
      Materials and Methods: Respiratory-gated three-dimensional balanced steady-state
      free-precession scans were conducted on 31 healthy subjects using two methods (A
      and B) for visualizing the LGV with hepatopetal flow. In method A, two time
      spatial labeling inversion pulses (Time-SLIP) were placed on the whole abdomen
      and the area from the gastric fornix to the upper body, excluding the LGV area.
      In method B, nonselective inversion recovery pulse was used and one Time-SLIP was
      placed on the esophagogastric junction. The detectability and consistency of LGV
      were evaluated using the two methods and ultrasonography (US). Results: Left
      gastric veins by method A, B, and US were detected in 30 (97%), 24 (77%), and 23
      (74%) subjects, respectively. LGV flow by US was hepatopetal in 22 subjects and
      stagnant in one subject. All hepatopetal LGVs by US coincided with the visualized
      vessels in both methods. One subject with non-visualized LGV in method A showed
      stagnant LGV by US. Conclusion: Hepatopetal LGV could be selectively visualized
      by method A in healthy subjects.

PMID- 29353998
TI  - Diffusion-Weighted MRI for the Initial Viability Evaluation of Parasites in
      Hepatic Alveolar Echinococcosis: Comparison with Positron Emission Tomography.
AB  - Objective: More than 70% of hepatic alveolar echinococcosis (HAE) are inoperable.
      Thus, long-term, or even life-long, pharmacological treatment with benzimidazoles
      is necessary. For effective treatment, it is of great importance to employ
      imaging techniques to detect and monitor the non-resectable parasitic viability.
      Therefore, this study aimed to evaluate diffusion-weighted imaging (DWI) in
      assessing the viability of HAE in comparison to 18-fluoro-deoxyglucose (18F-FDG)
      positron emission tomography, combined with computed tomography (PET/CT).
      Materials and Methods: Positron emission tomography, computed tomography and DWI
      (b-values: 0, 800 s/mm2) were retrospectively analysed in eight patients with
      clinically-verified HAE to, generate the apparent diffusion coefficient (ADC)
      map. The activity of HAE lesions in both techniques were determined independently
      by two radiologists according to the following standard: (+), marked focally or
      perilesionally increased FDG uptake/high signal intensity; (-), a hepatic defect
      without FDG uptake/no high signal intensity. Every lesion's maximum standardized
      uptake value (SUVmax) on the PET/CT images and mean ADC values on the parametric
      ADC maps were measured respectively. Results of PET/CT and DWI were compared on a
      per-lesion-basis. Pearson's correlation coefficient was assessed for statistical
      analysis. Results: A total of 14 HAE lesions were detected. Eight lesions
      (diameter 3-15 cm) showed perilesional hyper-signal intensity on DWI. This was
      visualised on PET/CT as increased FDG uptake. They mainly existed in the lesion's
      border with normal liver parenchyma. Five lesions (diameter < 2 cm) were detected
      as nodular hyperintensity on DWI and a 'hot spot' on PET/CT in the same
      distribution. One patient, who had received oral drug therapy for three years
      showed significantly decreased perilesional hyperintensity on the DWI and a
      hepatic defect without any FDG uptake on PET/CT. Pearson's correlation
      coefficient indicated a significant inverse correlation of the ADC and the SUVmax
      (r = -0.67, p < 0.001). Conclusion: Diffusion-weighted imaging is capable of
      offering information on visually detecting the HAE lesions' viability and may be
      useful for routine application in the initial diagnosis of HAE.

PMID- 29353999
TI  - Impact of Pedal Arch Patency on Tissue Loss and Time to Healing in Diabetic
      Patients with Foot Wounds Undergoing Infrainguinal Endovascular
      Revascularization.
AB  - Objective: To retrospectively evaluate the impact of pedal arch quality on tissue
      loss and time to healing in diabetic patients with foot wounds undergoing
      infrainguinal endovascular revascularization. Materials and Methods: Between
      January 2014 and June 2015, 137 consecutive diabetic patients with foot wounds
      underwent infrainguinal endovascular revascularization (femoro-popliteal or below
      the-knee, arteries). Postprocedural angiography of the foot was used to divide
      the patients into the following three groups according to the pedal arch status:
      complete pedal arch (CPA), incomplete pedal arch (IPA), and absent pedal arch
      (APA). Time to healing and estimated 1-year outcomes in terms of freedom from
      minor amputation, limb salvage, and survival were evaluated and compared among
      the three groups. Results: Postprocedural angiography showed the presence of a
      CPA in 42 patients (30.7%), IPA in 60 patients (43.8%), and APA in 35 patients
      (25.5%). Healing within 3 months from the procedure was achieved in 21 patients
      with CPA (50%), 17 patients with IPA (28.3%), and in 7 patients with APA (20%) (p
      = 0.01). There was a significant difference in terms of 1-year freedom from minor
      amputation among the three groups (CPA 84.1% vs. IPA 82.4% vs. APA 48.9%, p =
      0.001). Estimated 1-year limb salvage was significantly better in patients with
      CPA (CPA 100% vs. IPA 93.8% vs. APA 70.1%, p < 0.001). Estimated 1-year survival
      was significantly better in patients with CPA (CPA 90% vs. IPA 80.8% vs. APA
      62.7%, p = 0.004). Conclusion: Pedal arch status has a positive impact on time to
      healing, limb salvage, and survival in diabetic patients with foot wounds
      undergoing infrainguinal endovascular revascularization.

PMID- 29354000
TI  - Ultrasound-Guided Intraoperative Radiofrequency Ablation and Surgical Resection
      for Liver Metastasis from Malignant Gastrointestinal Stromal Tumors.
AB  - Objective: To evaluate the effectiveness, safety, and feasibility of
      intraoperative radiofrequency ablation (IORFA) under ultrasound guidance for the
      treatment of liver metastases from gastrointestinal stromal tumors (GISTs).
      Materials and Methods: From August 2009 to February 2017, 24 patients with liver
      metastases of GISTs underwent IORFA, 14 underwent concurrent IORFA and primary
      GIST resection, and 10 underwent IORFA to treat hepatic recurrence after previous
      primary GIST resection. Seventy-six hepatic metastases were treated, of which 47
      were surgically resected and 29 underwent IORFA. All included patients received
      imatinib therapy as standard treatment before and after IORFA or surgical
      resection. A retrospective medical record review was conducted, and follow-up
      data were collected. Technical success and effectiveness, overall and GIST
      specific survival, and complications were assessed. Results: The mean follow-up
      duration was 50.7 +/- 34.7 months. The technical success rate of IORFA was 100%.
      New metastases developed in three of the 24 patients (12.5%) following a complete
      response 16, 51, and 95 months after IORFA, respectively. The cumulative one-,
      three-, and five-year overall survival rates were 100, 94.4, and 87.7%,
      respectively. The one-, three-, and five-year GIST-related survival rates were
      100, 94.4, and 94.4%, respectively. Two major complications (biliary stricture
      and hepatic abscess) were observed. Conclusion: IORFA appears to be a feasible
      and safe treatment option for liver metastasis in patients with primary GISTs. In
      addition, IORFA and surgical resection may be complementary, helping to obtain
      complete response in cases of otherwise inoperable liver metastases secondary to
      GISTs.

PMID- 29354001
TI  - The Association between the Magnetic Resonance Imaging Findings of Adhesive
      Capsulitis and Shoulder Muscle Fat Quantification Using a Multi-Echo Dixon
      Method.
AB  - Objective: To investigate the association between the magnetic resonance imaging
      (MRI) findings of adhesive capsulitis and shoulder muscle fat percentages using a
      multi-echo Dixon method. Materials and Methods: Twenty-four patients with
      clinical diagnoses of adhesive capsulitis and either intact rotator cuffs or
      Ellman grade 1 partial tears as indicated by MRI scans were included. Two
      radiologists independently evaluated MRI scans of adhesive capsulitis as follows:
      presence or absence of axillary recess capsular and extracapsular
      hyperintensities; thickness of the coracohumeral ligament; thickness of abnormal
      rotator interval soft tissue; and thickness of glenoidal/humeral axillary recess
      capsules. Fat quantifications of the supraspinatus, infraspinatus, teres minor,
      subscapularis, teres major and posterior deltoid muscles were performed using
      multi-echo Dixon imaging at three locations. Inter-rater agreement was assessed.
      Differences in fat percentages were assessed and correlations between fat
      percentages and quantitative measurements were evaluated. Results: The fat
      percentage of the supraspinatus was significantly higher in patients with
      extracapsular hyperintensity (present, 3.00 +/- 1.74%; absent, 1.81 +/- 0.80%; p
      = 0.022). There were positive correlations between the fat percentage of the
      teres minor and the thicknesses of the abnormal rotator interval soft tissue (r =
      0.494, p = 0.014) and the glenoidal axillary recess capsule (r = 0.475, p =
      0.019). After controlling for the effects of age, sex and clinical stage, the
      relationship between the teres minor fat percentage and the thickness of the
      abnormal rotator interval soft tissue was statistically significant (r = 0.384, p
      = 0.048). Inter-rater agreement was almost perfect for fat quantification
      (intraclass correlation coefficients [ICC] > 0.9) and qualitative analyses (k =
      0.824), but were variable for quantitative measurements (ICC, 0.170-0.606).
      Conclusion: Several MRI findings of adhesive capsulitis were significantly
      related to higher fat percentages of shoulder muscles.

PMID- 29354002
TI  - Cerebrospinal Fluid Dynamics in Patients with Multiple Sclerosis: The Role of
      Phase-Contrast MRI in the Differential Diagnosis of Active and Chronic Disease.
AB  - Objective: Multiple sclerosis (MS) is an inflammatory disease characterized by
      demyelinating plaques in the white matter. Chronic cerebrospinal venous
      insufficiency (CCSVI) has been proposed as a new hypothesis for the
      etiopathogenesis of MS disease. MS-CCSVI includes a significant decrease of
      cerebrospinal fluid (CSF) flow through the cerebral aqueduct secondary to an
      impaired venous outflow from the central nervous system. This study aimed to
      determine whether CSF flow dynamics are affected in MS patients and the
      contributions to differential diagnosis in active and chronic disease using phase
      contrast magnetic resonance imaging (PC-MRI). Materials and Methods: We studied
      16 MS patients with chronic plaques (group 1), 16 MS patients with active plaques
      enhanced on MRI (group 2), and 16 healthy controls (group 3). Quantitatively
      evaluation of the CSF flow was performed from the level of the cerebral aqueduct
      by PC-MRI. According to heart rates, 14-30 images were obtained in a cardiac
      cycle. Cardiac triggering was performed prospectively using finger
      plethysmography. Results: No statistically significant difference was found
      between the groups regarding average velocity, net forward volume and the average
      flow (p > 0.05). Compared with the controls, group 1 and group 2, showed a higher
      peak velocity (5.5 +/- 1.4, 4.9 +/- 1.0, and 4.3 +/- 1.3 cm/sec, respectively; p
      = 0.040), aqueductal area (5.0 +/- 1.3, 4.1 +/- 1.5, and 3.1 +/- 1.2 mm2,
      respectively; p = 0.002), forward volume (0.039 +/- 0.016, 0.031 +/- 0.013, and
      0.021 +/- 0.010 mL, respectively; p = 0.002) and reverse volume (0.027 +/- 0.016,
      0.018 +/- 0.009, and 0.012 +/- 0.006 mL, respectively; p = 0.000). There were no
      statistical significance between the MS patients with chronic plaques and active
      plaques except for reverse volume. The MS patients with chronic plaques showed a
      significantly higher reverse volume (p = 0.000). Conclusion: This study indicated
      that CSF flow is affected in MS patients, contrary to the hypothesis that CCSVI
      induced CSF flow decreases in MS patients. These findings may be explained by
      atrophy-dependent ventricular dilatation, which may occur at every stage of MS.

PMID- 29354003
TI  - Diffusion-Weighted MR Imaging of Unicystic Odontogenic Tumors for Differentiation
      of Unicystic Ameloblastomas from Keratocystic Odontogenic Tumors.
AB  - Objective: Differentiating unicystic ameloblastomas from keratocystic odontogenic
      tumors (KCOT) is necessary for the planning of different treatment strategies;
      however, it is difficult based on conventional CT and MR sequences alone. The
      purpose of this study was to investigate the utility of diffusion-weighted
      imaging (DWI) and apparent diffusion coefficients (ADCs) in the differentiation
      of the two tumors. Materials and Methods: We prospectively studied 40 patients
      with odontogenic cysts and tumors of the maxillomandibular region using
      conventional MR imaging and DWI. ADCs were measured using 2 b factors (500 and
      1000). Results: Unicystic ameloblastomas (n = 11) showed free diffusion on DWI
      and a mean ADC value of 2.309 +/- 0.17 * 10-3 mm2/s. KCOT (n = 15) showed
      restricted diffusion on DWI with a mean ADC value of 0.923 +/- 0.20 * 10-3 mm2/s.
      The ADC values of unicystic ameloblastomas were significantly higher than those
      of KCOT (p < 0.001, Mann-Whitney U-test). An ADC cut-off value of 2.0 * 10-3
      mm2/s to differentiate KCOT and unicystic ameloblastomas resulted in a 100%
      sensitivity and 100% specificity. Dentigerous cysts (n = 3) showed restricted
      diffusion on DWI and similar ADC values (1.257 +/- 0.05 * 10-3 mm2/s) to those of
      KCOT. Conclusion: Diffusion-weighted imaging and ADC determination can be used as
      an adjuvant tool to differentiate between unicystic ameloblastomas and KCOT,
      although the ADC values of dentigerous cysts overlap with those of KCOT.

PMID- 29354004
TI  - Magnetic Resonance Image Texture Analysis of the Periaqueductal Gray Matter in
      Episodic Migraine Patients without T2-Visible Lesions.
AB  - Objective: The periaqueductal gray matter (PAG), a small midbrain structure,
      presents dysfunction in migraine. However, the precise neurological mechanism is
      still not well understood. Herein, the aim of this study was to investigate the
      texture characteristics of altered PAG in episodic migraine (EM) patients based
      on high resolution brain structural magnetic resonance (MR) images. Materials and
      Methods: The brain structural MR images were obtained from 18 normal controls
      (NC), 18 EM patients and 16 chronic migraine (CM) patients using a 3T MR system.
      A PAG template was created using the International Consortium Brain Mapping 152
      gray matter model, and the individual PAG segment was developed by applying the
      deformation field from the structural image segment to the PAG template. A grey
      level co-occurrence matrix was used to calculate the texture parameters including
      the angular second moment (ASM), contrast, correlation, inverse difference moment
      (IDM) and entropy. Results: There was a significant difference for ASM, IDM and
      entropy in the EM group (998.629 +/- 0.162 * 10-3, 999.311 +/- 0.073 * 10-3,
      916.354 +/- 0.947 * 10-5) compared to that found in the NC group (998.760 +/-
      0.110 * 10-3, 999.358 +/- 0.037 * 10-3 and 841.198 +/- 0.575 * 10-5) (p < 0.05).
      The entropy was significantly lower among the patients with CM (864.116 +/- 0.571
      * 10-5) than that found among patients with EM (p < 0.05). The area under the
      receiver operating characteristic curve was 0.776 and 0.750 for ASM and entropy
      in the distinction of the EM from NC groups, respectively. ASM was negatively
      related to disease duration (DD) and the Migraine Disability Assessment Scale
      (MIDAS) scores in the EM group, and entropy was positively related to DD and
      MIDAS in the EM group (p < 0.05). Conclusion: The present study identified
      altered MR image texture characteristics of the PAG in EM. The identified texture
      characteristics could be considered as imaging biomarkers for EM.

PMID- 29354005
TI  - In Vivo Assessment of Neurodegeneration in Type C Niemann-Pick Disease by IDEAL
      IQ.
AB  - Objective: To noninvasively assess the neurodegenerative changes in the brain of
      patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue
      with the iterative decomposition of water and fat with echo asymmetry and least
      square estimation-iron quantification (IDEAL-IQ). Materials and Methods: Routine
      brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served
      as control) were performed on 12 patients with type C Niemann-Pick disease (4
      males and 8 females; age range, 15-61 years; mean age, 36 years) and 20 healthy
      subjects (10 males and 10 females; age range, 20-65 years; mean age, 38 years).
      The regions with lesion and the normal appearing regions (NARs) of patients were
      measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the
      lipid peak on 1H-MRS. Results: Niemann-Pick type C patients showed a higher
      fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and
      NARs (3.7-4.9%, p < 0.05 and 1.8-3.0%, p < 0.05, respectively), as compared to
      healthy controls (HCs) (1.2-2.3%). After treatment, the fat/water signal
      intensity ratio decreased (2.2-3.4%), but remained higher than in the HCs (p <
      0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the
      same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients
      was detectable by IDEAL-IQ instead of 1H-MRS. Conclusion: The findings of this
      study suggested that IDEAL-IQ may be useful as a noninvasive and objective method
      in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to
      quantitatively measure the brain parenchymal adipose content and monitor patient
      follow-up after treatment of NPC.

PMID- 29354006
TI  - Findings of Single-Photon Emission Computed Tomography and Its Relation with
      Quantitative Coronary Angiography in Patients with Significant Stenosis of the
      Left Main Coronary Artery.
AB  - Objective: Unrecognized left main coronary artery disease (LMCD) is often fatal;
      however, accuracy of non-invasive tests for diagnosing LMCD is still
      unsatisfactory. This study was performed to elucidate single-photon emission
      computed tomography (SPECT) detection of LMCD using quantitative coronary
      angiography (QCA) data. Materials and Methods: Fifty-five patients (39 men; mean
      age, 68.1 +/- 10.9 years) diagnosed with significant left main (LM) stenosis (>=
      50%) by invasive coronary angiography (ICA) were retrospectively reviewed. All
      study patients underwent SPECT with pharmacologic stress within 30 days of ICA.
      All coronary lesions were quantified via QCA, and SPECT findings were compared
      with QCA results. Results: Only four patients (7.3%) had isolated LMCD; all
      others had combined significant stenosis (>= 70%) of one or more other epicardial
      coronary arteries. Patients with more severe coronary artery disease tended to
      have higher values for summed difference scores in a greater number of regions,
      but the specific pattern was not clearly defined. Summed stress score of SPECT
      did not differ according to LM stenosis severity. Only three patients (5.4%) had
      a typical LM pattern of reversible perfusion defect on SPECT. A significant
      negative linear correlation between stenosis severity and stress perfusion
      percent was found in the left anterior descending artery region (r = -0.455, p <
      0.001) but not in the left circumflex artery. Conclusion: Single-photon emission
      computed tomography findings were heterogeneous, not specific and poorly
      correlated to QCA data in patients with significant LMCD. This may be due to
      highly prevalent significant stenosis of other epicardial coronary arteries.

PMID- 29354007
TI  - Four-Dimensional CT of the Diaphragm in Children: Initial Experience.
AB  - Objective: To evaluate the technical feasibility of four-dimensional (4D) CT for
      the functional evaluation of the pediatric diaphragm. Materials and Methods: In
      22 consecutive children (median age 3.5 months, age range 3 days-3 years), 4D CT
      was performed to assess diaphragm motion. Diaphragm abnormalities were
      qualitatively evaluated and diaphragm motion was quantitatively measured on 4D
      CT. Lung density changes between peak inspiration and expiration were measured in
      the basal lung parenchyma. The diaphragm motions and lung density changes
      measured on 4D CT were compared between various diaphragm conditions. In 11 of
      the 22 children, chest sonography was available for comparison. Results: Four
      dimensional CT demonstrated normal diaphragm (n = 8), paralysis (n = 10),
      eventration (n = 3), and diffusely decreased motion (n = 1). Chest sonography
      demonstrated normal diaphragm (n = 2), paralysis (n = 6), eventration (n = 2),
      and right pleural effusion (n = 1). The sonographic findings were concordant with
      the 4D CT findings in 90.9% (10/11) of the patients. In diaphragm paralysis, the
      affected diaphragm motion was significantly decreased compared with the
      contralateral normal diaphragm motion (-1.1 +/- 2.2 mm vs. 7.6 +/- 3.8 mm, p =
      0.005). The normal diaphragms showed significantly greater motion than the
      paralyzed diaphragms (4.5 +/- 2.1 mm vs. -1.1 +/- 2.2 mm, p < 0.0001), while the
      normal diaphragm motion was significantly smaller than the motion of the
      contralateral normal diaphragm in paralysis (4.5 +/- 2.1 mm vs. 7.6 +/- 3.8 mm, p
      = 0.01). Basal lung density change of the affected side was significantly smaller
      than that of the contralateral side in diaphragm paralysis (89 +/- 73 Hounsfield
      units [HU] vs. 180 +/- 71 HU, p = 0.03), while no significant differences were
      found between the normal diaphragms and the paralyzed diaphragms (136 +/- 66 HU
      vs. 89 +/- 73 HU, p = 0.1) or between the normal diaphragms and the contralateral
      normal diaphragms in paralysis (136 +/- 66 HU vs. 180 +/- 71 HU, p = 0.1).
      Conclusion: The functional evaluation of the pediatric diaphragm is feasible with
      4D CT in select children.

PMID- 29354008
TI  - Quantitative Image Quality and Histogram-Based Evaluations of an Iterative
      Reconstruction Algorithm at Low-to-Ultralow Radiation Dose Levels: A Phantom
      Study in Chest CT.
AB  - Objective: To describe the quantitative image quality and histogram-based
      evaluation of an iterative reconstruction (IR) algorithm in chest computed
      tomography (CT) scans at low-to-ultralow CT radiation dose levels. Materials and
      Methods: In an adult anthropomorphic phantom, chest CT scans were performed with
      128-section dual-source CT at 70, 80, 100, 120, and 140 kVp, and the reference
      (3.4 mGy in volume CT Dose Index [CTDIvol]), 30%-, 60%-, and 90%-reduced
      radiation dose levels (2.4, 1.4, and 0.3 mGy). The CT images were reconstructed
      by using filtered back projection (FBP) algorithms and IR algorithm with
      strengths 1, 3, and 5. Image noise, signal-to-noise ratio (SNR), and contrast-to
      noise ratio (CNR) were statistically compared between different dose levels, tube
      voltages, and reconstruction algorithms. Moreover, histograms of subtraction
      images before and after standardization in x- and y-axes were visually compared.
      Results: Compared with FBP images, IR images with strengths 1, 3, and 5
      demonstrated image noise reduction up to 49.1%, SNR increase up to 100.7%, and
      CNR increase up to 67.3%. Noteworthy image quality degradations on IR images
      including a 184.9% increase in image noise, 63.0% decrease in SNR, and 51.3%
      decrease in CNR, and were shown between 60% and 90% reduced levels of radiation
      dose (p < 0.0001). Subtraction histograms between FBP and IR images showed
      progressively increased dispersion with increased IR strength and increased dose
      reduction. After standardization, the histograms appeared deviated and ragged
      between FBP images and IR images with strength 3 or 5, but almost normally
      distributed between FBP images and IR images with strength 1. Conclusion: The IR
      algorithm may be used to save radiation doses without substantial image quality
      degradation in chest CT scanning of the adult anthropomorphic phantom, down to
      approximately 1.4 mGy in CTDIvol (60% reduced dose).

PMID- 29354009
TI  - Assessing the Blood Supply Status of the Focal Ground-Glass Opacity in Lungs
      Using Spectral Computed Tomography.
AB  - Objective: To exploit material decomposition analysis in dual-energy spectral
      computed tomography (CT) to assess the blood supply status of the ground-glass
      opacity (GGO) in lungs. Materials and Methods: This retrospective study included
      48 patients with lung adenocarcinoma, who underwent a contrast-enhanced dual
      energy spectral CT scan before treatment (53 GGOs in total). The iodine
      concentration (IC) and water content (WC) of the GGO, the contralateral and
      ipsilateral normal lung tissues were measured in the arterial phase (AP) and
      their differences were analyzed. IC, normalized IC (NIC), and WC values were
      compared between the pure ground-glass opacity (pGGO) and the mixed ground-glass
      opacity (mGGO), and between the group of preinvasive lesions and the minimally
      invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) groups. Results:
      The values of pGGO (IC = 20.9 +/- 6.2 mg/mL and WC = 345.1 +/- 87.1 mg/mL) and
      mGGO (IC = 23.8 +/- 8.3 mg/mL and WC = 606.8 +/- 124.5 mg/mL) in the AP were
      significantly higher than those of the contralateral normal lung tissues (IC =
      15.0 +/- 4.9 mg/mL and WC = 156.4 +/- 36.8 mg/mL; IC = 16.2 +/- 5.7 mg/mL and WC
      = 169.4 +/- 41.0 mg/mL) and ipsilateral normal lung tissues (IC = 15.1 +/- 6.2
      mg/mL and WC = 156.3 +/- 38.8 mg/mL; IC = 15.9 +/- 6.0 mg/mL and WC = 174.7 +/-
      39.2 mg/mL; all p < 0.001). After normalizing the data according to the values of
      the artery, pGGO (NIC = 0.1 and WC = 345.1 +/- 87.1 mg/mL) and mGGO (NIC = 0.2
      and WC = 606.8 +/- 124.5 mg/mL) were statistically different (p = 0.049 and p <
      0.001, respectively), but not for the IC value (p = 0.161). The WC values of the
      group with preinvasive lesions and MIA (345.4 +/- 96.1 mg/mL) and IA (550.1 +/-
      158.2 mg/mL) were statistically different (p < 0.001). Conclusion: Using dual
      energy spectral CT and material decomposition analysis, the IC in GGO can be
      quantitatively measured which can be an indicator of the blood supply status in
      the GGO.

PMID- 29354010
TI  - Significance of Low-Attenuation Cluster Analysis on Quantitative CT in the
      Evaluation of Chronic Obstructive Pulmonary Disease.
AB  - Objective: To assess clinical feasibility of low-attenuation cluster analysis in
      evaluation of chronic obstructive pulmonary disease (COPD). Materials and
      Methods: Subjects were 199 current and former cigarette smokers that underwent CT
      for quantification of COPD and had physiological measurements. Quantitative CT
      (QCT) measurements included low-attenuation area percent (LAA%) (voxels <= -950
      Hounsfield unit [HU]), and two-dimensional (2D) and three-dimensional D values of
      cluster analysis at three different thresholds of CT value (-856, -910, and -950
      HU). Correlation coefficients between QCT measurements and physiological indices
      were calculated. Multivariable analyses for percentage of predicted forced
      expiratory volume at one second (%FEV1) was performed including sex, age, body
      mass index, LAA%, and D value had the highest correlation coefficient with %FEV1
      as independent variables. These analyses were conducted in subjects including
      those with mild COPD (global initiative of chronic obstructive lung disease stage
      = 0-II). Results: LAA% had a higher correlation coefficient (-0.549, p < 0.001)
      with %FEV1 than D values in subjects while 2D D-910HU (-0.350, p < 0.001)
      revealed slightly higher correlation coefficient than LAA% (-0.343, p < 0.001) in
      subjects with mild COPD. Multivariable analyses revealed that LAA% and 2D D value
      910HU were significant independent predictors of %FEV1 in subjects and that only
      2D D value-910HU revealed a marginal p value (0.05) among independent variables
      in subjects with mild COPD. Conclusion: Low-attenuation cluster analysis provides
      incremental information regarding physiologic severity of COPD, independent of
      LAA%, especially with mild COPD.

PMID- 29354011
TI  - Application of Deconvolution Algorithm of Point Spread Function in Improving
      Image Quality: An Observer Preference Study on Chest Radiography.
AB  - Objective: To evaluate the preference of observers for image quality of chest
      radiography using the deconvolution algorithm of point spread function (PSF)
      (TRUVIEW ART algorithm, DRTECH Corp.) compared with that of original chest
      radiography for visualization of anatomic regions of the chest. Materials and
      Methods: Prospectively enrolled 50 pairs of posteroanterior chest radiographs
      collected with standard protocol and with additional TRUVIEW ART algorithm were
      compared by four chest radiologists. This algorithm corrects scattered signals
      generated by a scintillator. Readers independently evaluated the visibility of 10
      anatomical regions and overall image quality with a 5-point scale of preference.
      The significance of the differences in reader's preference was tested with a
      Wilcoxon's signed rank test. Results: All four readers preferred the images
      applied with the algorithm to those without algorithm for all 10 anatomical
      regions (mean, 3.6; range, 3.2-4.0; p < 0.001) and for the overall image quality
      (mean, 3.8; range, 3.3-4.0; p < 0.001). The most preferred anatomical regions
      were the azygoesophageal recess, thoracic spine, and unobscured lung. Conclusion:
      The visibility of chest anatomical structures applied with the deconvolution
      algorithm of PSF was superior to the original chest radiography.

PMID- 29354012
TI  - In-vivo Visualization of Iron Oxide Enhancement in Focal Pulmonary Inflammatory
      Lesions Using a Three-Dimensional Radial Gradient-Echo-Based Ultrashort Echo Time
      Sequence: A Preliminary Study.
AB  - Objective: To preliminarily evaluate technical feasibility of a dual-echo
      ultrashort echo time (UTE) subtraction MR imaging by using concurrent dephasing
      and excitation (CODE) sequence for visualization of iron-oxide enhancement in
      focal inflammatory pulmonary lesions. Materials and Methods: A UTE pulmonary MR
      imaging before and after the injection of clinically usable superparamagnetic
      iron-oxide nanoparticles, ferumoxytol, was conducted using CODE sequence with
      dual echo times of 0.14 ms for the first echo and 4.15 ms for the second echo on
      3T scanner in two rabbits concurrently having granulomatous lung disease and lung
      cancer in separate lobes. A mean ratio of standardized signal intensity (SI) was
      calculated for comparison of granulomatous lesion and cancer at first echo,
      second echo, and subtracted images. Lesions were pathologically evaluated with
      Prussian blue and immunohistochemistry staining. Results: Post-contrast
      subtracted CODE images visualized exclusive enhancement of iron oxide in
      granulomatous disease, but not in the cancer (mean ratio of SI, 2.15 +/- 0.68 for
      granulomatous lesion versus 1.00 +/- 0.07 for cancer; p value = 0.002). Prussian
      blue and corresponding anti-rabbit macrophage IgG-staining suggested an
      intracellular uptake of iron-oxide nanoparticles in macrophages of granulomatous
      lesions. Conclusion: Dual-echo UTE subtraction MR imaging using CODE sequence
      depicts an exclusive positive enhancement of iron-oxide nanoparticle in rabbits
      in focal granulomatous inflammatory lesions.

PMID- 29354013
TI  - Ultrasonographic Interval Changes in Solid Thyroid Nodules after Ultrasonography
      Guided Fine-Needle Aspiration.
AB  - Objective: None of the previous studies have investigated the interval change in
      ultrasonography (US) features of solid thyroid nodules (STNs) after US-guided
      fine-needle aspiration (US-FNA). This study aimed to assess the prevalence and
      characteristics of US interval changes in STNs after US-FNA. Materials and
      Methods: This study included 257 STNs in 257 patients in whom thyroid US and
      initial US-FNA had been performed by two radiologists from January 2015 to June
      2015. One of the radiologists performed single needle puncture in all cases,
      whereas the other radiologist used double or triple needle punctures. Follow-up
      US examinations were performed after 12.0 +/- 6.0 months. We evaluated the
      prevalence and characteristics of post-FNA US interval changes through a
      retrospective analysis. In addition, multiple factors were correlated with post
      FNA US interval changes. Results: The number of needle punctures was one (n =
      91), two (n = 163), and three (n = 3). Of the 257 STNs (mean diameter, 11.9 mm)
      in 257 patients, 35 (13.6%) showed an interval change in US features on follow-up
      US. Among them, 17 STNs (6.6%) showed newly developed malignant US features,
      including hypoechogenicity (n = 5), microcalcifications (n = 2), a spiculated
      margin (n = 4), hypoechogenicity with a spiculated margin (n = 5), and
      microcalcifications with non-parallel orientation (n = 1). Between patients who
      showed presence and absence of US interval changes, there were no significant
      differences in patient age, sex, nodule size, dichotomization, and location,
      Korean Thyroid Imaging Reporting and Data System categorization after FNA,
      practitioners involved, number of needle punctures, cytological findings, and
      interval between FNA and US follow-up (p > 0.05). Conclusion: Awareness of US
      interval changes after US-FNA of STNs may be helpful for the management of STNs.

PMID- 29354014
TI  - Efficacy and Safety of Radiofrequency Ablation for Benign Thyroid Nodules: A
      Prospective Multicenter Study.
AB  - Objective: To assess the efficacy and safety of thyroid radiofrequency (RF)
      ablation for benign thyroid nodules by trained radiologists according to a
      unified protocol in a multi-center study. Materials and Methods: From 2010 to
      2011, 345 nodules from 345 patients (M:F = 43:302; mean age +/- SD = 46.0 +/-
      12.7 years, range = 15-79) who met eligibility criteria were enrolled from five
      institutions. At pre-ablation, the mean volume was 14.2 +/- 13.2 mL (1.1-80.8
      mL). For 12 months or longer after treatment, 276 lesions, consisting of 248
      solid and 28 predominantly cystic nodules, were followed. All operators performed
      RF ablation with a cool-tip RF system and two standard techniques (a transisthmic
      approach and the moving-shot technique). Volume reduction at 12 months after RF
      ablation (the primary outcome), therapeutic success, improvement of symptoms as
      well as of cosmetic problems, and complications were evaluated. Multiple linear
      regression analysis was applied to identify factors that were independently
      predictive of volume reduction. Results: The mean volume reduction at 12 months
      was 80.3% (n = 276) and at the 24-, 36-, 48-, and 60-month follow-ups 84.3% (n =
      198), 89.2% (n = 128), 91.9% (n = 57), and 95.3% (n = 6), respectively. Our
      therapeutic success was 97.8%. Both mean symptom and cosmetic scores showed
      significant improvements (p < 0.001). The rate of major complications was 1.0%
      (3/276). Solidity and applied energy were independent factors that predicted
      volume reduction. Conclusion: Radiofrequency ablation performed by trained
      radiologists from multiple institutions using a unified protocol and similar
      devices was effective and safe for treating benign thyroid nodules.

PMID- 29354016
TI  - RE: Novel Application of Quantitative Single-Photon Emission Computed
      Tomography/Computed Tomography to Predict Early Response to Methimazole in
      Graves' Disease.

PMID- 29354017
TI  - Modelling vocabulary development among multilingual children prior to and
      following the transition to school entry.
AB  - Differences between monolingual and multilingual vocabulary development have been
      observed but few studies provide a longitudinal perspective on vocabulary
      development before and following school entry. This study compares vocabulary
      growth profiles of 106 multilingual children to 211 monolingual peers before and
      after school entry to examine whether: (1) school entry coincides with different
      rates of vocabulary growth compared to prior to school entry, (2) compared to
      monolingual peers, multilingual children show different vocabulary sizes or rates
      of vocabulary growth, (3) the age of onset of second-language acquisition for
      multilingual children is associated with vocabulary size or rate of vocabulary
      growth, and (4) the sociolinguistic context of the languages spoken by
      multilingual children is associated with vocabulary size or rate of vocabulary
      growth. Results showed increases in vocabulary size across time for all children,
      with a steeper increase prior to school entry. A significant difference between
      monolingual and multilingual children who speak a minority language was observed
      with regards to vocabulary size at school entry and vocabulary growth prior to
      school entry, but growth rate differences were no longer present following school
      entry. Taken together, results suggest that which languages children speak may
      matter more than being multilingual per se.

PMID- 29354015
TI  - Quality of Life in Patients Treated with Percutaneous Laser Ablation for Non
      Functioning Benign Thyroid Nodules: A Prospective Single-Center Study.
AB  - Objective: While many studies have reported that laser ablation (LA) for benign
      non-fuctioning thyroid nodules is efficacious in reducing nodular volume and neck
      symptoms, none have described changes in quality of life (QoL). The purpose of
      this study was to report post-LA changes in QoL in our cohort of patients.
      Materials and Methods: Fourteen patients with benign thyroid nodules were
      involved in a prospective, single-center study and underwent a single session of
      LA. We evaluated the following: changes in nodule volume, thyroid function, and
      autoimmunity; adverse events during and after LA; changes in neck discomfort by
      means of a visual analogic scale (VAS) at one week and 1, 3, 6, and 12 months;
      and changes in QoL through the 13-scale Thyroid-specific Patient Reported Outcome
      (ThyPRO) questionnaire at 1, 3, 6, and 12 months. ThyPRO is a validated
      questionnaire for thyroid diseases, which consists of 13 scales with multiple
      choice answers. They investigate several aspects of life that may be impaired by
      goiter-related compression symptoms, by esthetic alterations and by hypo- or
      hyperthyroidism. Results: Nodule volume decrease was -37 +/- 23%, -55 +/- 22%, 
      53 +/- 25%, -58 +/- 25% (p < 0.01 vs. baseline) at the first, third, sixth, and
      twelfth month, respectively. No hypothyroidism or positivization of autoimmunity
      was observed. There were no major complications during or after LA. After LA, VAS
      scores improved significantly from 1 week onwards in 100% of patients, while a
      significant improvement was seen in the goiter symptoms score after one month,
      and in the general score and mean values of ThyPRO after six months. Scores on
      the other ThyPRO scales did not change significantly. Conclusion: Laser ablation
      is safe and effective in reducing nodule volume and neck symptoms; this is
      confirmed by improvements in the goiter scale, general score, and mean values of
      ThyPRO and in the VAS score.

PMID- 29354018
TI  - Joint nonparametric correction estimator for excess relative risk regression in
      survival analysis with exposure measurement error.
AB  - Observational epidemiological studies often confront the problem of estimating
      exposure-disease relationships when the exposure is not measured exactly. In the
      paper, we investigate exposure measurement error in excess relative risk
      regression, which is a widely used model in radiation exposure effect research.
      In the study cohort, a surrogate variable is available for the true unobserved
      exposure variable. The surrogate variable satisfies a generalized version of the
      classical additive measurement error model, but it may or may not have repeated
      measurements. In addition, an instrumental variable is available for individuals
      in a subset of the whole cohort. We develop a nonparametric correction (NPC)
      estimator using data from the subcohort, and further propose a joint
      nonparametric correction (JNPC) estimator using all observed data to adjust for
      exposure measurement error. An optimal linear combination estimator of JNPC and
      NPC is further developed. The proposed estimators are nonparametric, which are
      consistent without imposing a covariate or error distribution, and are robust to
      heteroscedastic errors. Finite sample performance is examined via a simulation
      study. We apply the developed methods to data from the Radiation Effects Research
      Foundation, in which chromosome aberration is used to adjust for the effects of
      radiation dose measurement error on the estimation of radiation dose responses.

PMID- 29354019
TI  - Recent Progress in Decarboxylative Oxidative Cross-Coupling for Biaryl Synthesis.
AB  - The beginning of the 21st century has seen tremendous growth in the field of
      decarboxylative activation. Benzoic acid derivatives are now recognised as atom
      economic alternatives to traditional cross-coupling partners, and they also
      benefit from being inexpensive, readily available and shelf-stable reagents. In
      this microreview we discuss recent developments in the coupling of benzoic acid
      derivatives either with an arene or with a second benzoic acid derivative, a
      process often termed decarboxylative oxidative cross-coupling. These procedures
      offer great promise for the development of highly selective and atom-economic
      cross-couplings.

PMID- 29354020
TI  - Drinking patterns at the sub-national level: What do they tell us about drinking
      cultures in European countries?
AB  - Aim: A drinking pattern is not only a major drinking variable, but is also one
      indicator of a country's drinking culture. In the present study, we examine
      drinking patterns within and across the neighbouring countries of Denmark and
      Germany. The aim of the research is to determine to what extent drinking patterns
      differ or are shared at the sub-national level in the two countries. Method: Data
      came from the German 2012 Epidemiological Survey of Substance Use (n 9084) 18-64
      years (response rate 54%), and the Centre for Alcohol and Drug Research's 2011
      Danish national survey (n = 5133) 15-79 years (response rate 64%), which was
      reduced to a common age range, producing a final of 4016. The drinking pattern
      variable included abstention, moderate drinking, heavy drinking, risky single
      occasion drinking (RSOD), and was investigated with bivariate statistics and
      gender-specific hierarchical cluster analysis. Results: For men three clusters
      emerged: one highlighting abstention and RSOD, moderate/heavy drinking, RSOD and
      RSOD heavy drinking. For women, two clusters appeared: one highlighting
      abstention and moderate/ heavy drinking and the other highlighting RSOD and RSDO
      heavy drinking. The clusters revealed different geographical patterning: for men,
      a west vs. east divide; for women, a north-south gradient. Conclusions: The
      analysis could identify for each gender clusters representing both separate and
      shared drinking patterns as well as distinctive geographical placements. This new
      knowledge can contribute to a new understanding of the dynamics of drinking
      cultures and could indicate new approaches to prevention efforts and policy
      initiatives.

PMID- 29354021
TI  - 117th Annual Meeting Medical Library Association, Inc. Seattle, WA May 26-31,
      2017.

PMID- 29354022
TI  - Trait Stress Resistance and Dynamic Stress Dissipation on Health and Well-Being:
      The Reservoir Model.
AB  - Daily data from the NDHWB (n = 783; age range 37-90) were analyzed to produce
      'dynamic characteristic' estimates of stress input and dissipation. These were
      used in multi-level modeling (with age and trait stress resistance) to predict
      depression and health trajectories. Main effects suggest that dissipation and
      stress resistance predict lower depression and better health, but lower stress
      input was only related to lower depression. Interactions revealed that subjects
      with above average stress resistance had lower depression irrespective of their
      ability to dissipate stress, but for individuals low in trait resistance those
      with better stress dissipation show lower depression and better health.

PMID- 29354023
TI  - Effect of Oxygen Sputter Pressure on the Structural, Morphological and Optical
      Properties of ZnO Thin Films for Gas Sensing Application.
AB  - ZnO thin films were prepared on glass substrates at low (5 * 10-4 mbar) and high
      (3 * 10-3 mbar) sputter pressure using dc reactive magnetron sputtering. The
      structural, morphological, compositional and optical properties of the thin films
      were investigated. XRD patterns of both films confirmed the polycrystalline
      nature of the films with hexagonal Wurtzite structure. SEM study indicates that
      the surface of the film formed at high sputter pressure was more uniform, compact
      and porous in nature. From the EDAX analysis, no other characteristic peaks of
      other impurities were observed and the formation of single phase of ZnO was
      confirmed. From the study of photoluminescence, three peaks were observed, one
      strong near band-edge emission at 390 nm followed by weak and broad visible
      emissions around 420-480 nm. Room temperature ammonia sensing characteristics of
      ZnO nanothin films formed at higher sputter pressure were studied for different
      ammonia vapour concentration levels. The response of the Ammonia sensor at room
      temperature (30  degrees C) operation was observed to be of high sensitivity with
      quick response and recovery times.

PMID- 29354024
TI  - High-throughput extraction and quantification method for targeted metabolomics in
      murine tissues.
AB  - Introduction: Global metabolomics analyses using body fluids provide valuable
      results for the understanding and prediction of diseases. However, the mechanism
      of a disease is often tissue-based and it is advantageous to analyze metabolomic
      changes directly in the tissue. Metabolomics from tissue samples faces many
      challenges like tissue collection, homogenization, and metabolite extraction.
      Objectives: We aimed to establish a metabolite extraction protocol optimized for
      tissue metabolite quantification by the targeted metabolomics AbsoluteIDQTM p180
      Kit (Biocrates). The extraction method should be non-selective, applicable to
      different kinds and amounts of tissues, monophasic, reproducible, and amenable to
      high throughput. Methods: We quantified metabolites in samples of eleven murine
      tissues after extraction with three solvents (methanol, phosphate buffer,
      ethanol/phosphate buffer mixture) in two tissue to solvent ratios and analyzed
      the extraction yield, ionization efficiency, and reproducibility. Results: We
      found methanol and ethanol/phosphate buffer to be superior to phosphate buffer in
      regard to extraction yield, reproducibility, and ionization efficiency for all
      metabolites measured. Phosphate buffer, however, outperformed both organic
      solvents for amino acids and biogenic amines but yielded unsatisfactory results
      for lipids. The observed matrix effects of tissue extracts were smaller or in a
      similar range compared to those of human plasma. Conclusion: We provide for each
      murine tissue type an optimized high-throughput metabolite extraction protocol,
      which yields the best results for extraction, reproducibility, and quantification
      of metabolites in the p180 kit. Although the performance of the extraction
      protocol was monitored by the p180 kit, the protocol can be applicable to other
      targeted metabolomics assays.

PMID- 29354025
TI  - Parathyroid carcinoma: an unusual presentation of a rare neoplasm.
AB  - Parathyroid carcinoma is an extremely rare malignant endocrine neoplasm that is
      very challenging in its diagnosis as well as its treatment. Clinically the
      disease is detected earlier in patients who present with hyperparathyroidism with
      signs of profound hypercalcemia. Differentiation between benign and malignant
      disease of the parathyroid is challenging both for the clinician and for the
      pathologist. Complete surgical resection at the time of first operation offers
      the best chance of cure. Even after radical excision which is the standard
      management, local recurrence and metastases are frequent. The disease usually has
      a slow indolent course and most patients suffer from complications of
      hypercalcemia rather than tumor invasion or metastasis. We report a case of a 31
      year-old woman who presented with renal colic. Various hematological, biochemical
      and radiological investigations were performed and a slightly enlarged right
      parathyroid was found. A clinical diagnosis of parathyroid adenoma was made and a
      right parathyroidectomy was done. Intraoperatively the surgeon had no suspicion
      of malignancy but microscopically the lesion was malignant and a final diagnosis
      of parathyroid carcinoma was rendered based on the criteria of invasion. Since
      there is no gold standard, a multidisciplinary approach, including the entire
      clinical, biochemical, radiological and pathological profile of the disease aids
      in an accurate diagnosis. Here we are reporting a case of a functional
      parathyroid carcinoma presenting in a relatively young patient with all the
      biochemical and radiological investigations and intraoperative findings pointing
      towards a benign parathyroid disease.

PMID- 29354026
TI  - Imaging of Neuronal Activity in Awake Mice by Measurements of Flavoprotein
      Autofluorescence Corrected for Cerebral Blood Flow.
AB  - Green fluorescence imaging (e.g., flavoprotein autofluorescence imaging, FAI) can
      be used to measure neuronal activity and oxygen metabolism in living brains
      without expressing fluorescence proteins. It is useful for understanding the
      mechanism of various brain functions and their abnormalities in age-related brain
      diseases. However, hemoglobin in cerebral blood vessels absorbs green
      fluorescence, hampering accurate assessments of brain function in animal models
      with cerebral blood vessel dysfunctions and subsequent cerebral blood flow (CBF)
      alterations. In the present study, we developed a new method to correct FAI
      signals for hemoglobin-dependent green fluorescence reductions by simultaneous
      measurements of green fluorescence and intrinsic optical signals. Intrinsic
      optical imaging enabled evaluations of light absorption and scatters by
      hemoglobin, which could then be applied to corrections of green fluorescence
      intensities. Using this method, enhanced flavoprotein autofluorescence by sensory
      stimuli was successfully detected in the brains of awake mice, despite increases
      of CBF, and hemoglobin interference. Moreover, flavoprotein autofluorescence
      could be properly quantified in a resting state and during sensory stimulation by
      a CO2 inhalation challenge, which modified vascular responses without overtly
      affecting neuronal activities. The flavoprotein autofluorescence signal data
      obtained here were in good agreement with the previous findings from a condition
      with drug-induced blockade of cerebral vasodilation, justifying the current
      assaying methodology. Application of this technology to studies on animal models
      of brain diseases with possible changes of CBF, including age-related
      neurological disorders, would provide better understanding of the mechanisms of
      neurovascular coupling in pathological circumstances.

PMID- 29354028
TI  - Drosophila melanogaster White Mutant w1118 Undergo Retinal Degeneration.
AB  - Key scientific discoveries have resulted from genetic studies of Drosophila
      melanogaster, using a multitude of transgenic fly strains, the majority of which
      are constructed in a genetic background containing mutations in the white gene.
      Here we report that white mutant flies from w1118 strain undergo retinal
      degeneration. We observed also that w1118 mutants have progressive loss of
      climbing ability, shortened life span, as well as impaired resistance to various
      forms of stress. Retinal degeneration was abolished by transgenic expression of
      mini-white+ in the white null background w1118 . We conclude that beyond the
      classical eye-color phenotype, mutations in Drosophila white gene could impair
      several biological functions affecting parameters like mobility, life span and
      stress tolerance. Consequently, we suggest caution and attentiveness during the
      interpretation of old experiments employing white mutant flies and when planning
      new ones, especially within the research field of neurodegeneration and
      neuroprotection. We also encourage that the use of w1118 strain as a wild-type
      control should be avoided.

PMID- 29354027
TI  - Metabolic Abnormalities of Erythrocytes as a Risk Factor for Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a slowly progressive, neurodegenerative disorder of
      uncertain etiology. According to the amyloid cascade hypothesis, accumulation of
      non-soluble amyloid beta peptides (Abeta) in the Central Nervous System (CNS) is
      the primary cause initiating a pathogenic cascade leading to the complex
      multilayered pathology and clinical manifestation of the disease. It is,
      therefore, not surprising that the search for mechanisms underlying cognitive
      changes observed in AD has focused exclusively on the brain and Abeta-inducing
      synaptic and dendritic loss, oxidative stress, and neuronal death. However, since
      Abeta depositions were found in normal non-demented elderly people and in many
      other pathological conditions, the amyloid cascade hypothesis was modified to
      claim that intraneuronal accumulation of soluble Abeta oligomers, rather than
      monomer or insoluble amyloid fibrils, is the first step of a fatal cascade in AD.
      Since a characteristic reduction of cerebral perfusion and energy metabolism
      occurs in patients with AD it is suggested that capillary distortions commonly
      found in AD brain elicit hemodynamic changes that alter the delivery and
      transport of essential nutrients, particularly glucose and oxygen to neuronal and
      glial cells. Another important factor in tissue oxygenation is the ability of
      erythrocytes (red blood cells, RBC) to transport and deliver oxygen to tissues,
      which are first of all dependent on the RBC antioxidant and energy metabolism,
      which finally regulates the oxygen affinity of hemoglobin. In the present review,
      we consider the possibility that metabolic and antioxidant defense alterations in
      the circulating erythrocyte population can influence oxygen delivery to the
      brain, and that these changes might be a primary mechanism triggering the glucose
      metabolism disturbance resulting in neurobiological changes observed in the AD
      brain, possibly related to impaired cognitive function. We also discuss the
      possibility of using erythrocyte biochemical aberrations as potential tools that
      will help identify a risk factor for AD.

PMID- 29354030
TI  - Sphingolipid Metabolism Is Dysregulated at Transcriptomic and Metabolic Levels in
      the Spinal Cord of an Animal Model of Amyotrophic Lateral Sclerosis.
AB  - Lipid metabolism is drastically dysregulated in amyotrophic lateral sclerosis and
      impacts prognosis of patients. Animal models recapitulate alterations in the
      energy metabolism, including hypermetabolism and severe loss of adipose tissue.
      To gain insight into the molecular mechanisms underlying disease progression in
      amyotrophic lateral sclerosis, we have performed RNA-sequencing and lipidomic
      profiling in spinal cord of symptomatic SOD1G86R mice. Spinal transcriptome of
      SOD1G86R mice was characterized by differential expression of genes related to
      immune system, extracellular exosome, and lysosome. Hypothesis-driven
      identification of metabolites showed that lipids, including
      sphingomyelin(d18:0/26:1), ceramide(d18:1/22:0), and phosphatidylcholine(o
      22:1/20:4) showed profound altered levels. A correlation between disease severity
      and gene expression or metabolite levels was found for sphingosine,
      ceramide(d18:1/26:0), Sgpp2, Sphk1, and Ugt8a. Joint-analysis revealed a
      significant enrichment of glycosphingolipid metabolism in SOD1G86R mice, due to
      the down-regulation of ceramide, glucosylceramide, and lactosylceramide and the
      overexpression of genes involved in their recycling in the lysosome. A drug-gene
      interaction database was interrogated to identify potential drugs able to
      modulate the dysregulated genes from the signaling pathway. Our results suggest
      that complex lipids are pivotally changed during the first phase of motor
      symptoms in an animal model of amyotrophic lateral sclerosis.

PMID- 29354031
TI  - Myelinating Schwann Cell Polarity and Mechanically-Driven Myelin Sheath
      Elongation.
AB  - Myelin sheath geometry, encompassing myelin sheath thickness relative to
      internodal length, is critical to optimize nerve conduction velocity and these
      parameters are carefully adjusted by the myelinating cells in mammals. In the
      central nervous system these adjustments could regulate neuronal activities while
      in the peripheral nervous system they lead to the optimization and the
      reliability of the nerve conduction velocity. However, the physiological and
      cellular mechanisms that underlie myelin sheath geometry regulation are not yet
      fully elucidated. In peripheral nerves the myelinating Schwann cell uses several
      molecular mechanisms to reach and maintain the correct myelin sheath geometry,
      such that myelin sheath thickness and internodal length are regulated
      independently. One of these mechanisms is the epithelial-like cell polarization
      process that occurs during the early phases of the myelin biogenesis. Epithelial
      cell polarization factors are known to control cell size and morphology in
      invertebrates and mammals making these processes critical in the organogenesis.
      Correlative data indicate that internodal length is regulated by postnatal body
      growth that elongates peripheral nerves in mammals. In addition, the mechanical
      stretching of peripheral nerves in adult animals shows that myelin sheath length
      can be increased by mechanical cues. Recent results describe the important role
      of YAP/TAZ co-transcription factors during Schwann cell myelination and their
      functions have linked to the mechanotransduction through the HIPPO pathway and
      the epithelial polarity factor Crb3. In this review the molecular mechanisms that
      govern mechanically-driven myelin sheath elongation and how a Schwann cell can
      modulate internodal myelin sheath length, independent of internodal thickness,
      will be discussed regarding these recent data. In addition, the potential
      relevance of these mechanosensitive mechanisms in peripheral pathologies will be
      highlighted.

PMID- 29354033
TI  - Enhanced Transmission at the Calyx of Held Synapse in a Mouse Model for Angelman
      Syndrome.
AB  - The neurodevelopmental disorder Angelman syndrome (AS) is characterized by
      intellectual disability, motor dysfunction, distinct behavioral aspects, and
      epilepsy. AS is caused by a loss of the maternally expressed UBE3A gene, and many
      of the symptoms are recapitulated in a Ube3a mouse model of this syndrome. At the
      cellular level, changes in the axon initial segment (AIS) have been reported, and
      changes in vesicle cycling have indicated the presence of presynaptic deficits.
      Here we studied the role of UBE3A in the auditory system by recording synaptic
      transmission at the calyx of Held synapse in the medial nucleus of the trapezoid
      body (MNTB) through in vivo whole cell and juxtacellular recordings. We show that
      MNTB principal neurons in Ube3a mice exhibit a hyperpolarized resting membrane
      potential, an increased action potential (AP) amplitude and a decreased AP half
      width. Moreover, both the pre- and postsynaptic AP in the calyx of Held synapse
      of Ube3a mice showed significantly faster recovery from spike depression. An
      increase in AIS length was observed in the principal MNTB neurons of Ube3a mice,
      providing a possible substrate for these gain-of-function changes. Apart from the
      effect on APs, we also observed that EPSPs showed decreased short-term synaptic
      depression (STD) during long sound stimulations in AS mice, and faster recovery
      from STD following these tones, which is suggestive of a presynaptic gain-of
      function. Our findings thus provide in vivo evidence that UBE3A plays a critical
      role in controlling synaptic transmission and excitability at excitatory
      synapses.

PMID- 29354032
TI  - Proteomic Dissection of Nanotopography-Sensitive Mechanotransductive Signaling
      Hubs that Foster Neuronal Differentiation in PC12 Cells.
AB  - Neuronal cells are competent in precisely sensing nanotopographical features of
      their microenvironment. The perceived microenvironmental information will be
      "interpreted" by mechanotransductive processes and impacts on neuronal
      functioning and differentiation. Attempts to influence neuronal differentiation
      by engineering substrates that mimic appropriate extracellular matrix (ECM)
      topographies are hampered by the fact that profound details of mechanosensing/
      transduction complexity remain elusive. Introducing omics methods into these
      biomaterial approaches has the potential to provide a deeper insight into the
      molecular processes and signaling cascades underlying mechanosensing/
      transduction but their exigence in cellular material is often opposed by
      technical limitations of major substrate top-down fabrication methods. Supersonic
      cluster beam deposition (SCBD) allows instead the bottom-up fabrication of
      nanostructured substrates over large areas characterized by a quantitatively
      controllable ECM-like nanoroughness that has been recently shown to foster neuron
      differentiation and maturation. Exploiting this capacity of SCBD, we challenged
      mechanosensing/-transduction and differentiative behavior of neuron-like PC12
      cells with diverse nanotopographies and/or changes of their biomechanical status,
      and analyzed their phosphoproteomic profiles in these settings. Versatile
      proteins that can be associated to significant processes along the
      mechanotransductive signal sequence, i.e., cell/cell interaction, glycocalyx and
      ECM, membrane/f-actin linkage and integrin activation, cell/substrate
      interaction, integrin adhesion complex, actomyosin organization/cellular
      mechanics, nuclear organization, and transcriptional regulation, were affected.
      The phosphoproteomic data suggested furthermore an involvement of ILK, mTOR, Wnt,
      and calcium signaling in these nanotopography- and/or cell mechanics-related
      processes. Altogether, potential nanotopography-sensitive mechanotransductive
      signaling hubs participating in neuronal differentiation were dissected.

PMID- 29354029
TI  - Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan.
AB  - Microglia are the predominant immune response cells and professional phagocytes
      of the central nervous system (CNS) that have been shown to be important for
      brain development and homeostasis. These cells present a broad spectrum of
      phenotypes across stages of the lifespan and especially in CNS diseases. Their
      prevalence in all neurological pathologies makes it pertinent to reexamine their
      distinct roles during steady-state and disease conditions. A major question in
      the field is determining whether the clustering and phenotypical transformation
      of microglial cells are leading causes of pathogenesis, or potentially
      neuroprotective responses to the onset of disease. The recent explosive growth in
      our understanding of the origin and homeostasis of microglia, uncovering their
      roles in shaping of the neural circuitry and synaptic plasticity, allows us to
      discuss their emerging functions in the contexts of cognitive control and
      psychiatric disorders. The distinct mesodermal origin and genetic signature of
      microglia in contrast to other neuroglial cells also make them an interesting
      target for the development of therapeutics. Here, we review the physiological
      roles of microglia, their contribution to the effects of environmental risk
      factors (e.g., maternal infection, early-life stress, dietary imbalance), and
      their impact on psychiatric disorders initiated during development (e.g., Nasu
      Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett
      syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder
      (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder
      (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep
      disorders). Furthermore, we discuss the changes in microglial functions in the
      context of cognitive aging, and review their implication in neurodegenerative
      diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into
      account the recent identification of microglia-specific markers, and the
      availability of compounds that target these cells selectively in vivo, we
      consider the prospect of disease intervention via the microglial route.

PMID- 29354035
TI  - Hippocampal Astrocytes in Migrating and Wintering Semipalmated Sandpiper Calidris
      pusilla.
AB  - Seasonal migratory birds return to the same breeding and wintering grounds year
      after year, and migratory long-distance shorebirds are good examples of this.
      These tasks require learning and long-term spatial memory abilities that are
      integrated into a navigational system for repeatedly locating breeding,
      wintering, and stopover sites. Previous investigations focused on the
      neurobiological basis of hippocampal plasticity and numerical estimates of
      hippocampal neurogenesis in birds but only a few studies investigated potential
      contributions of glial cells to hippocampal-dependent tasks related to migration.
      Here we hypothesized that the astrocytes of migrating and wintering birds may
      exhibit significant morphological and numerical differences connected to the long
      distance flight. We used as a model the semipalmated sandpiper Calidris pusilla,
      that migrates from northern Canada and Alaska to South America. Before the
      transatlantic non-stop long-distance component of their flight, the birds make a
      stopover at the Bay of Fundy in Canada. To test our hypothesis, we estimated
      total numbers and compared the three-dimensional (3-D) morphological features of
      adult C. pusilla astrocytes captured in the Bay of Fundy (n = 249 cells) with
      those from birds captured in the coastal region of Braganca, Brazil, during the
      wintering period (n = 250 cells). Optical fractionator was used to estimate the
      number of astrocytes and for 3-D reconstructions we used hierarchical cluster
      analysis. Both morphological phenotypes showed reduced morphological complexity
      after the long-distance non-stop flight, but the reduction in complexity was much
      greater in Type I than in Type II astrocytes. Coherently, we also found a
      significant reduction in the total number of astrocytes after the transatlantic
      flight. Taken together these findings suggest that the long-distance non-stop
      flight altered significantly the astrocytes population and that morphologically
      distinct astrocytes may play different physiological roles during migration.

PMID- 29354034
TI  - Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex.
AB  - Prefrontal cortex is a hub for attention processing and receives abundant
      innervation from cholinergic and serotonergic afferents. A growing body of
      evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing
      influences on tasks requiring attention, but the underlying neurophysiology of
      their opposition is unclear. One candidate target population is medial prefrontal
      layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as
      well as feed-forward excitation of cortical interneurons. Here, we assess the
      response of these neurons to ACh and 5-HT using whole cell recordings in acute
      brain slices from mouse cortex. With application of exogenous agonists, we show
      that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh
      and 5-HT exerting opposite effects on excitability across a number of
      concentrations. Next, we tested the responses of layer 6 pyramidal neurons to
      optogenetic release of endogenous ACh or 5-HT. These experiments were performed
      in brain slices from transgenic mice expressing channelrhodopsin in either ChAT
      expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light
      evoked endogenous neuromodulation recapitulated the effects of exogenous
      neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by
      ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh
      significantly suppressed the excitation of pyramidal neurons in prefrontal layer
      6. Taken together, this work suggests that the major corticothalamic layer of
      prefrontal cortex is a substrate for opposing modulatory influences on neuronal
      activity that could have implications for regulation of attention.

PMID- 29354036
TI  - Facilitation of Function and Manipulation Knowledge of Tools Using Transcranial
      Direct Current Stimulation (tDCS).
AB  - Using a variety of tools is a common and essential component of modern human
      life. Patients with brain damage or neurological disorders frequently have
      cognitive deficits in their recognition and manipulation of tools. In this study,
      we focused on improving tool-related cognition using transcranial direct current
      stimulation (tDCS). Converging evidence from neuropsychology, neuroimaging and
      non- invasive brain stimulation has identified the anterior temporal lobe (ATL)
      and inferior parietal lobule (IPL) as brain regions supporting action semantics.
      We observed enhanced performance in tool cognition with anodal tDCS over ATL and
      IPL in two cognitive tasks that require rapid access to semantic knowledge about
      the function or manipulation of common tools. ATL stimulation improved access to
      both function and manipulation knowledge of tools. The effect of IPL stimulation
      showed a trend toward better manipulation judgments. Our findings support
      previous studies of tool semantics and provide a novel approach for manipulation
      of underlying circuits.

PMID- 29354037
TI  - Pulsed Stimuli Elicit More Robust Multisensory Enhancement than Expected.
AB  - Neurons in the superior colliculus (SC) integrate cross-modal inputs to generate
      responses that are more robust than to either input alone, and are frequently
      greater than their sum (superadditive enhancement). Previously, the principles of
      a real-time multisensory transform were identified and used to accurately predict
      a neuron's responses to combinations of brief flashes and noise bursts. However,
      environmental stimuli frequently have more complex temporal structures that
      elicit very different response dynamics than previously examined. The present
      study tested whether such stimuli (i.e., pulsed) would be treated similarly by
      the multisensory transform. Pulsing visual and auditory stimuli elicited
      responses composed of higher discharge rates that had multiple peaks temporally
      aligned to the stimulus pulses. Combinations pulsed cues elicited multiple peaks
      of superadditive enhancement within the response window. Measured over the entire
      response, this resulted in larger enhancements than expected given enhancements
      elicited by non-pulsed ("sustained") stimuli. However, as with sustained stimuli,
      the dynamics of multisensory responses to pulsed stimuli were highly related to
      the temporal dynamics of the unisensory inputs. This suggests that the specific
      characteristics of the multisensory transform are not determined by the external
      features of the cross-modal stimulus configuration; rather the temporal structure
      and alignment of the unisensory inputs is the dominant driving factor in the
      magnitudes of the multisensory product.

PMID- 29354039
TI  - Automated Assessment of Endpoint and Kinematic Features of Skilled Reaching in
      Rats.
AB  - Background: Neural injury to the motor cortex may result in long-term
      impairments. As a model for human impairments, rodents are often used to study
      deficits related to reaching and grasping, using the single-pellet reach-to-grasp
      task. Current assessments of this test capture mostly endpoint outcome. While
      qualitative features have been proposed, they usually involve manual scoring.
      Objective: To detect three phases of movement during the single-pellet reach-to
      grasp test and assess completion of each phase. To automatically monitor rat
      forelimb trajectory so as to extract kinematics and classify phase outcome.
      Methods: A top-view camera is used to monitor three rats during training, healthy
      and impaired testing, over 33 days. By monitoring the coordinates of the forelimb
      tip along with the position of the pellet, the algorithm divides a trial into
      reaching, grasping and retraction. Unfulfilling any of the phases results in one
      of three possible errors: miss, slip or drop. If all phases are complete, the
      outcome label is success. Along with endpoints, movement kinematics are assessed:
      variability, convex hull, mean and maximum reaching speed, length of trajectory
      and peak forelimb extension. Results: The set of behavior endpoints was extended
      to include miss, slip, drop and success rate. The labeling algorithm was tested
      on pre- and post-lesion datasets, with overall accuracy rates of 86% and 92%,
      respectively. These endpoint features capture a drop in skill after motor
      cortical lesion as the success rate of 59.6 +/- 11.8% pre-lesion decreases to
      13.9 +/- 8.2% post-lesion, along with a significant increase in miss rate from
      7.2 +/- 6.7% pre-lesion to 50.2 +/- 18.7% post-lesion. Kinematics reveals
      individual-specific strategies of improvement during training, with a common
      trend of trajectory variability decreasing with success. Correlations between
      kinematics and endpoints reveal a more complex pattern of relationships during
      rehabilitation (18 significant pairs of features) than during training (nine
      correlated pairs). Conclusion: Extended endpoint outcomes and kinematics of
      reaching and grasping are captured automatically with a robust computer program.
      Both endpoints and kinematics capture intra-animal drop in skill after a motor
      cortical lesion. Correlations between kinematics and endpoints change from
      training to rehabilitation, suggesting different mechanisms that underlie motor
      improvement.

PMID- 29354038
TI  - Hippocampal Remapping and Its Entorhinal Origin.
AB  - The activity of hippocampal cell ensembles is an accurate predictor of the
      position of an animal in its surrounding space. One key property of hippocampal
      cell ensembles is their ability to change in response to alterations in the
      surrounding environment, a phenomenon called remapping. In this review article,
      we present evidence for the distinct types of hippocampal remapping. The
      progressive divergence over time of cell ensembles active in different
      environments and the transition dynamics between pre-established maps are
      discussed. Finally, we review recent work demonstrating that hippocampal
      remapping can be triggered by neurons located in the entorhinal cortex.

PMID- 29354040
TI  - Mirror Box Training in Hemiplegic Stroke Patients Affects Body Representation.
AB  - The brain integrates multisensory inputs coming from the body (i.e.,
      proprioception, tactile sensations) and the world that surrounds it (e.g., visual
      information). In this way, it is possible to build supra-modal and coherent
      mental representations of our own body, in order to process sensory events and to
      plan movements and actions in space. Post-stroke acquired motor deficits affect
      the ability to move body parts and to interact with objects. This may, in turn,
      impair the brain representation of the affected body part, resulting in a further
      increase of disability and motor impairment. To the aim of improving any putative
      derangements of body representation induced by the motor deficit, here we used
      the Mirror Box (MB). MB is a rehabilitative tool aimed at restoring several
      pathological conditions where body representation is affected, including post
      stroke motor impairments. In this setting, observing the reflection of the intact
      limb in the mirror, while the affected one is hidden behind the mirror, can exert
      a positive influence upon different clinical conditions from chronic pain to
      motor deficits. Such results are thought to be mediated by a process of
      embodiment of the mirror reflection, which would be integrated into the
      representation of the affected limb. A group of 45 post-stroke patients was
      tested before and after performing a MB motor training in two conditions, one
      with the mirror between the hands and one without it, so that patients could see
      their impaired limb directly. A forearm bisection task, specifically designed to
      measure the metric representation of the body (i.e., size), was used as dependent
      variable. Results showed that, at baseline, the forearm bisection is shifted
      proximally, compatibly with a shrink of the metric representation of the affected
      arm towards the shoulder. However, following the MB session bisection scores
      shifted distally, compatibly with a partial correction of the metric
      representation of that arm. The effects showed some variability with the
      laterality of the lesion and the duration of the illness. The present results
      call for a possible role of the MB as a tool for improving altered body
      representation following post-stroke motor impairments.

PMID- 29354041
TI  - Longitudinal Brain Development of Numerical Skills in Typically Developing
      Children and Children with Developmental Dyscalculia.
AB  - Developmental dyscalculia (DD) is a learning disability affecting the acquisition
      of numerical-arithmetical skills. Studies report persistent deficits in number
      processing and aberrant functional activation of the fronto-parietal numerical
      network in DD. However, the neural development of numerical abilities has been
      scarcely investigated. The present paper provides a first attempt to investigate
      behavioral and neural trajectories of numerical abilities longitudinally in
      typically developing (TD) and DD children. During a study period of 4 years, 28
      children (8-11 years) were evaluated twice by means of neuropsychological tests
      and a numerical order fMRI paradigm. Over time, TD children improved in numerical
      abilities and showed a consistent and well-developed fronto-parietal network. In
      contrast, DD children revealed persistent deficits in number processing and
      arithmetic. Brain imaging results of the DD group showed an age-related
      activation increase in parietal regions (intraparietal sulcus), pointing to a
      delayed development of number processing areas. Besides, an activation increase
      in frontal areas was observed over time, indicating the use of compensatory
      mechanisms. In conclusion, results suggest a continuation in neural development
      of number representation in DD, whereas the neural network for simple ordinal
      number estimation seems to be stable or show only subtle changes in TD children
      over time.

PMID- 29354042
TI  - Neural Correlates of Racial Ingroup Bias in Observing Computer-Animated Social
      Encounters.
AB  - Despite evidence for the role of group membership in the neural correlates of
      social cognition, the mechanisms associated with processing non-verbal behaviors
      displayed by racially ingroup vs. outgroup members remain unclear. Here, 20
      Caucasian participants underwent fMRI recording while observing social encounters
      with ingroup and outgroup characters displaying dynamic and static non-verbal
      behaviors. Dynamic behaviors included approach and avoidance behaviors, preceded
      or not by a handshake; both dynamic and static behaviors were followed by
      participants' ratings. Behaviorally, participants showed bias toward their
      ingroup members, demonstrated by faster/slower reaction times for evaluating
      ingroup static/approach behaviors, respectively. At the neural level, despite
      overall similar responses in the action observation network to ingroup and
      outgroup encounters, the medial prefrontal cortex showed dissociable activation,
      possibly reflecting spontaneous processing of ingroup static behaviors and
      positive evaluations of ingroup approach behaviors. The anterior cingulate and
      superior frontal cortices also showed sensitivity to race, reflected in
      coordinated and reduced activation for observing ingroup static behaviors.
      Finally, the posterior superior temporal sulcus showed uniquely increased
      activity to observing ingroup handshakes. These findings shed light on the
      mechanisms of racial ingroup bias in observing social encounters, and have
      implications for understanding factors related to successful interactions with
      individuals from diverse backgrounds.

PMID- 29354043
TI  - An fMRI-Neuronavigated Chronometric TMS Investigation of V5 and Intraparietal
      Cortex in Motion Driven Attention.
AB  - The timing of networked brain activity subserving motion driven attention in
      humans is currently unclear. Functional MRI (fMRI)-neuronavigated chronometric
      transcranial magnetic stimulation (TMS) was used to investigate critical times of
      parietal cortex involvement in motion driven attention. In particular, we were
      interested in the relative critical times for two intraparietal sulcus (IPS)
      sites in comparison to that previously identified for motion processing in area
      V5, and to explore potential earlier times of involvement. fMRI was used to
      individually localize V5 and middle and posterior intraparietal sulcus (mIPS;
      pIPS) areas active for a motion driven attention task, prior to TMS
      neuronavigation. Paired-pulse TMS was applied during performance of the same task
      at stimulus onset asynchronies (SOAs) ranging from 0 to 180 ms. There were no
      statistically significant decreases in performance accuracy for trials where TMS
      was applied to V5 at any SOA, though stimulation intensity was lower for this
      site than for the parietal sites. For TMS applied to mIPS, there was a trend
      toward a relative decrease in performance accuracy at the 150 ms SOA, as well as
      a relative increase at 180 ms. There was no statistically significant effect
      overall of TMS applied to pIPS, however, there appeared a potential trend toward
      a decrease in performance at the 0 ms SOA. Overall, these results provide some
      patterns of potential theoretical interest to follow up in future studies.

PMID- 29354044
TI  - Effects of Acute Alcohol Intoxication on Empathic Neural Responses for Pain.
AB  - The questions whether and how empathy for pain can be modulated by acute alcohol
      intoxication in the non-dependent population remain unanswered. To address these
      questions, a double-blind, placebo-controlled, within-subject study design was
      adopted in this study, in which healthy social drinkers were asked to complete a
      pain-judgment task using pictures depicting others' body parts in painful or non
      painful situations during fMRI scanning, either under the influence of alcohol
      intoxication or placebo conditions. Empathic neural activity for pain was reduced
      by alcohol intoxication only in the dorsal anterior cingulate cortex (dACC). More
      interestingly, we observed that empathic neural activity for pain in the right
      anterior insula (rAI) was significantly correlated with trait empathy only after
      alcohol intoxication, along with impaired functional connectivity between the rAI
      and the fronto-parietal attention network. Our results reveal that alcohol
      intoxication not only inhibits empathic neural responses for pain but also leads
      to trait empathy inflation, possibly via impaired top-down attentional control.
      These findings help to explain the neural mechanism underlying alcohol-related
      social problems.

PMID- 29354046
TI  - Re-run, Repeat, Reproduce, Reuse, Replicate: Transforming Code into Scientific
      Contributions.
AB  - Scientific code is different from production software. Scientific code, by
      producing results that are then analyzed and interpreted, participates in the
      elaboration of scientific conclusions. This imposes specific constraints on the
      code that are often overlooked in practice. We articulate, with a small example,
      five characteristics that a scientific code in computational science should
      possess: re-runnable, repeatable, reproducible, reusable, and replicable. The
      code should be executable (re-runnable) and produce the same result more than
      once (repeatable); it should allow an investigator to reobtain the published
      results (reproducible) while being easy to use, understand and modify (reusable),
      and it should act as an available reference for any ambiguity in the algorithmic
      descriptions of the article (replicable).

PMID- 29354045
TI  - Dopaminergic Therapy Increases Go Timeouts in the Go/No-Go Task in Patients with
      Parkinson's Disease.
AB  - Parkinson's disease (PD) is characterized by resting tremor, rigidity and
      bradykinesia. Dopaminergic medications such as L-dopa treat these motor symptoms,
      but can have complex effects on cognition. Impulse control is an essential
      cognitive function. Impulsivity is multifaceted in nature. Motor impulsivity
      involves the inability to withhold pre-potent, automatic, erroneous responses. In
      contrast, cognitive impulsivity refers to improper risk-reward assessment guiding
      behavior. Informed by our previous research, we anticipated that dopaminergic
      therapy would decrease motor impulsivity though it is well known to enhance
      cognitive impulsivity. We employed the Go/No-go paradigm to assess motor
      impulsivity in PD. Patients with PD were tested using a Go/No-go task on and off
      their normal dopaminergic medication. Participants completed cognitive, mood, and
      physiological measures. PD patients on medication had a significantly higher
      proportion of Go trial Timeouts (i.e., trials in which Go responses were not
      completed prior to a deadline of 750 ms) compared to off medication (p = 0.01).
      No significant ON-OFF differences were found for Go trial or No-go trial response
      times (RTs), or for number of No-go errors. We interpret that dopaminergic
      therapy induces a more conservative response set, reflected in Go trial Timeouts
      in PD patients. In this way, dopaminergic therapy decreased motor impulsivity in
      PD patients. This is in contrast to the widely recognized effects of dopaminergic
      therapy on cognitive impulsivity leading in some patients to impulse control
      disorders. Understanding the nuanced effects of dopaminergic treatment in PD on
      cognitive functions such as impulse control will clarify therapeutic decisions.

PMID- 29354047
TI  - Commentary: Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release
      and is disrupted in Parkinson disease.

PMID- 29354049
TI  - Influences of 12-Week Physical Activity Interventions on TMS Measures of Cortical
      Network Inhibition and Upper Extremity Motor Performance in Older Adults-A
      Feasibility Study.
AB  - Objective: Data from previous cross-sectional studies have shown that an
      increased level of physical fitness is associated with improved motor dexterity
      across the lifespan. In addition, physical fitness is positively associated with
      increased laterality of cortical function during unimanual tasks; indicating that
      sedentary aging is associated with a loss of interhemispheric inhibition
      affecting motor performance. The present study employed exercise interventions in
      previously sedentary older adults to compare motor dexterity and measure of
      interhemispheric inhibition using transcranial magnetic stimulation (TMS) after
      the interventions. Methods: Twenty-one community-dwelling, reportedly sedentary
      older adults were recruited, randomized and enrolled to a 12-week aerobic
      exercise group or a 12-week non-aerobic exercise balance condition. The aerobic
      condition was comprised of an interval-based cycling "spin" activity, while the
      non-aerobic "balance" exercise condition involved balance and stretching
      activities. Participants completed upper extremity dexterity batteries and
      estimates of VO2max in addition to undergoing single (ipsilateral silent period
      iSP) and paired-pulse interhemispheric inhibition (ppIHI) in separate assessment
      sessions before and after study interventions. After each intervention during
      which heart rate was continuously recorded to measure exertion level (load),
      participants crossed over into the alternate arm of the study for an additional
      12-week intervention period in an AB/BA design with no washout period. Results:
      After the interventions, regardless of intervention order, participants in the
      aerobic spin condition showed higher estimated VO2max levels after the 12-week
      intervention as compared to estimated VO2max in the non-aerobic balance
      intervention. After controlling for carryover effects due to the study design,
      participants in the spin condition showed longer iSP duration than the balance
      condition. Heart rate load was more strongly correlated with silent period
      duration after the Spin condition than estimated VO2. Conclusions: Aging-related
      changes in cortical inhibition may be influenced by 12-week physical activity
      interventions when assessed with the iSP. Although inhibitory signaling is
      mediates both ppIHI and iSP measures each TMS modality likely employs distinct
      inhibitory networks, potentially differentially affected by aging. Changes in
      inhibitory function after physical activity interventions may be associated with
      improved dexterity and motor control at least as evidence from this feasibility
      study show.

PMID- 29354048
TI  - Aging and Network Properties: Stability Over Time and Links with Learning during
      Working Memory Training.
AB  - Growing evidence suggests that healthy aging affects the configuration of large
      scale functional brain networks. This includes reducing network modularity and
      local efficiency. However, the stability of these effects over time and their
      potential role in learning remain poorly understood. The goal of the present
      study was to further clarify previously reported age effects on "resting-state"
      networks, to test their reliability over time, and to assess their relation to
      subsequent learning during training. Resting-state fMRI data from 23 young (YA)
      and 20 older adults (OA) were acquired in 2 sessions 2 weeks apart. Graph
      theoretic analyses identified both consistencies in network structure and
      differences in module composition between YA and OA, suggesting topological
      changes and less stability of functional network configuration with aging. Brain
      wide, OA showed lower modularity and local efficiency compared to YA, consistent
      with the idea of age-related functional dedifferentiation, and these effects were
      replicable over time. At the level of individual networks, OA consistently showed
      greater participation and lower local efficiency and within-network connectivity
      in the cingulo-opercular network, as well as lower intra-network connectivity in
      the default-mode network and greater participation of the somato-sensorimotor
      network, suggesting age-related differential effects at the level of specialized
      brain modules. Finally, brain-wide network properties showed associations, albeit
      limited, with learning rates, as assessed with 10 days of computerized working
      memory training administered after the resting-state sessions, suggesting that
      baseline network configuration may influence subsequent learning outcomes.
      Identification of neural mechanisms associated with learning-induced plasticity
      is important for further clarifying whether and how such changes predict the
      magnitude and maintenance of training gains, as well as the extent and limits of
      cognitive transfer in both younger and older adults.

PMID- 29354051
TI  - Age-Related Differences in Hearing Function and Cochlear Morphology between Male
      and Female Fischer 344 Rats.
AB  - Fischer 344 (F344) rats represent a strain that is frequently used as a model for
      fast aging. In this study, we systematically compare the hearing function during
      aging in male and female F344 rats, by recording auditory brainstem responses
      (ABRs) and distortion product otoacoustic emissions (DPOAEs). In addition to
      this, the functional parameters are correlated with the cochlear histology. The
      parameters of the hearing function were not different in the young (3-month-old)
      male and female F344 rats; the gender differences occurred only in adult and aged
      animals. In 8-24-month-old males, the ABR thresholds were higher and the ABR
      amplitudes were smaller than those measured in females of the same age. There
      were no gender differences in the neural adaptation tested by recording ABRs,
      elicited by a series of clicks with varying inter-click interval (ICI).
      Amplitudes of DPOAEs in both the males and females decreased with age, but in the
      males, the decrease of DPOAE amplitudes was faster. In males older than 20
      months, the DPOAEs were practically absent, whereas in 20-24-month-old females,
      the DPOAEs were still measurable. There were no gender differences in the number
      of surviving outer hair cells (OHC) and the number of inner hair cell ribbon
      synapses in aged animals. The main difference was found in the stria vascularis
      (SV). Whereas the SV was well preserved in females up to the age of 24 months, in
      most of the age-matched males the SV was evidently deteriorated. The results
      demonstrate more pronounced age-related changes in the cochlear morphology,
      hearing thresholds, ABR amplitudes and DPOAE amplitudes in F344 males compared
      with females.

PMID- 29354050
TI  - Brain Network Modularity Predicts Exercise-Related Executive Function Gains in
      Older Adults.
AB  - Recent work suggests that the brain can be conceptualized as a network comprised
      of groups of sub-networks or modules. The extent of segregation between modules
      can be quantified with a modularity metric, where networks with high modularity
      have dense connections within modules and sparser connections between modules.
      Previous work has shown that higher modularity predicts greater improvements
      after cognitive training in patients with traumatic brain injury and in healthy
      older and young adults. It is not known, however, whether modularity can also
      predict cognitive gains after a physical exercise intervention. Here, we
      quantified modularity in older adults (N = 128, mean age = 64.74) who underwent
      one of the following interventions for 6 months (NCT01472744 on
      ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk),
      (2) aerobic exercise in the form of brisk walking plus nutritional supplement
      (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance
      instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains
      in cardiorespiratory fitness (CRF), with larger effects in both walking groups
      compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also
      improved in executive function (EF) as measured by reasoning, working memory, and
      task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF,
      higher baseline modularity was positively related to EF gains, even after
      controlling for age, in-scanner motion and baseline EF. No relationship between
      modularity and EF gains was observed in the Dance group, which did not show
      training-related gains in CRF or EF control. These results are consistent with
      previous studies demonstrating that individuals with a more modular brain network
      organization are more responsive to cognitive training. These findings suggest
      that the predictive power of modularity may be generalizable across interventions
      aimed to enhance aspects of cognition and that, especially in low-performing
      individuals, global network properties can capture individual differences in
      neuroplasticity.

PMID- 29354052
TI  - Caffeine Controls Glutamatergic Synaptic Transmission and Pyramidal Neuron
      Excitability in Human Neocortex.
AB  - Caffeine is the most widely used psychoactive drug, bolstering attention and
      normalizing mood and cognition, all functions involving cerebral cortical
      circuits. Whereas studies in rodents showed that caffeine acts through the
      antagonism of inhibitory A1 adenosine receptors (A1R), neither the role of A1R
      nor the impact of caffeine on human cortical neurons is known. We here provide
      the first characterization of the impact of realistic concentrations of caffeine
      experienced by moderate coffee drinkers (50 MUM) on excitability of pyramidal
      neurons and excitatory synaptic transmission in the human temporal cortex.
      Moderate concentrations of caffeine disinhibited several of the inhibitory A1R
      mediated effects of adenosine, similar to previous observations in the rodent
      brain. Thus, caffeine restored the adenosine-induced decrease of both intrinsic
      membrane excitability and excitatory synaptic transmission in the human pyramidal
      neurons through antagonism of post-synaptic A1R. Indeed, the A1R-mediated effects
      of endogenous adenosine were more efficient to inhibit synaptic transmission than
      neuronal excitability. This was associated with a distinct affinity of caffeine
      for synaptic versus extra-synaptic human cortical A1R, probably resulting from a
      different molecular organization of A1R in human cortical synapses. These
      findings constitute the first neurophysiological description of the impact of
      caffeine on pyramidal neuron excitability and excitatory synaptic transmission in
      the human temporal cortex, providing adequate ground for the effects of caffeine
      on cognition in humans.

PMID- 29354053
TI  - Activation of Dopamine D1-D2 Receptor Complex Attenuates Cocaine Reward and
      Reinstatement of Cocaine-Seeking through Inhibition of DARPP-32, ERK, and
      DeltaFosB.
AB  - A significant subpopulation of neurons in rat nucleus accumbens (NAc) coexpress
      dopamine D1 and D2 receptors, which can form a D1-D2 receptor complex, but their
      relevance in addiction is not known. The existence of the D1-D2 heteromer in the
      striatum of rat and monkey was established using in situ PLA, in situ FRET and co
      immunoprecipitation. In rat, D1-D2 receptor heteromer activation led to place
      aversion and abolished cocaine CPP and locomotor sensitization, cocaine
      intravenous self-administration and reinstatement of cocaine seeking, as well as
      inhibited sucrose preference and abolished the motivation to seek palatable food.
      Selective disruption of this heteromer by a specific interfering peptide induced
      reward-like effects and enhanced the above cocaine-induced effects, including at
      a subthreshold dose of cocaine. The D1-D2 heteromer activated Cdk5/Thr75-DARPP-32
      and attenuated cocaine-induced pERK and DeltaFosB accumulation, together with
      inhibition of cocaine-enhanced local field potentials in NAc, blocking thus the
      signaling pathway activated by cocaine: D1R/cAMP/PKA/Thr34-DARPP-32/pERK with
      DeltaFosB accumulation. In conclusion, our results show that the D1-D2 heteromer
      exerted tonic inhibitory control of basal natural and cocaine reward, and
      therefore initiates a fundamental physiologic function that limits the liability
      to develop cocaine addiction.

PMID- 29354054
TI  - The Opioid-Sparing Effect of Perioperative Dexmedetomidine Combined with
      Oxycodone Infusion during Open Hepatectomy: A Randomized Controlled Trial.
AB  - Background: A large right subcostal incision performed by open hepatectomy is
      associated with significant post-operative pain and distress. However, post
      operative analgesia solutions still need to be devised. We investigated the
      effects of intra- and post-operative infusion of dexmedetomidine (Dex) combined
      with oxycodone during open hepatectomy. Methods: In this prospective, randomized
      and double-blind investigation, 52 patients undergoing selective open hepatectomy
      were divided into Dex group (DEX infusion at an initial loading dose of 0.5
      MUg?kg-1 over 10 min before intubation then adjusted to a maintenance dose of 0.3
      MUg?kg-1?h-1 until incision suturing) or control (Con) group (0.9% sodium
      chloride was administered). Patient-controlled analgesia was administered for 48
      h after surgery (Dex group: 60 mg oxycodone and 360 MUg DEX diluted to 120 ml and
      administered at a bolus dose of 2 ml, with 5 min lockout interval and a 1 h limit
      of 20 ml. Con group: 60 mg oxycodone alone with the same regimen). The primary
      outcome was post-operative oxycodone consumption. The secondary outcomes included
      requirement of narcotic and vasoactive drugs, hemodynamics, incidence of adverse
      effects, satisfaction, first exhaust time, pain intensity, and the Ramsay
      Sedation Scale. Results: Post-operative oxycodone consumption was significantly
      reduced in Dex group from 4 to 48 h after surgery (P < 0.05). Heart rate in Dex
      group was statistically decreased from T1 (just before intubation) to T6 (20 min
      after arriving at the post-anesthesia care unit), while mean arterial pressure
      was significantly decreased from T1 to T3 (during surgical incision; P < 0.05).
      The consumption of propofol and remifentanil were significantly decreased in Dex
      group (P < 0.05). The VAS scores at rest at 1, 4, and 8 h and with cough at 24,
      and 48 h after surgery were lower, the first exhaust time were shorter,
      satisfaction with pain control was statistically higher and the incidence of
      nausea and vomiting was less in Dex group than in Con group (all P < 0.05).
      Conclusion: The combination of DEX and oxycodone could reduce oxycodone
      consumption and the incidence of nausea and vomiting, enhance the analgesic
      effect, improves patient satisfaction and shorten the first exhaust time.

PMID- 29354055
TI  - The Anti-atherosclerotic Effect of Paeonol against Vascular Smooth Muscle Cell
      Proliferation by Up-regulation of Autophagy via the AMPK/mTOR Signaling Pathway.
AB  - Introduction: Paeonol (2'-hydroxy-4'-methoxyacetophenone), isolated from moutan
      cortex, is an active component and has been shown to have anti-atherosclerotic
      and anti-proliferation effects on vascular smooth muscle cells (VSMCs). However,
      the possible role of Paeonol in protecting against VSMC proliferation as related
      to autophagy has yet to be elucidated. Materials and Methods: The athero
      protective effects of Paeonol were evaluated in apoE-/- mice. The effects of
      Paeonol on VSMC proliferation and autophagy were examined by staining alpha-SMA
      and LC3II spots in the media layer of apoE-/- mice, respectively. CCK8 and BrdU
      assays were used to investigate the effects of Paeonol on cell proliferation in
      vitro. The autophagic levels in VSMCs were evaluated by detecting LC3II
      accumulation and p62 degradation by immunoblot analysis. To investigate if
      Paeonol could prevent VSMCs proliferation through autophagy induction, we tested
      the change in autophagy and cell proliferation by inhibition of autophagy. The
      levels of the AMPK/mTOR pathway in autophagy regulation were detected by
      immunoblot analysis. An AMPK inhibitor and si-AMPK transfection in VSMCs was used
      to confirm whether AMPK activity plays a key role in autophagy regulation of
      Paeonol. Results:In vivo experiments confirmed that Paeonol restricted
      atherosclerosis development and decreased the amount of VSMCs in the media layer
      of apoE-/- mice. Paeonol increased protein levels of LC3II and the presence of
      autophagosomes in the media layer of arteries, which implies that Paeonol may
      induce VSMCs autophagy in vivo. Paeonol showed potential in inhibiting ox-LDL
      induced proliferation in vitro experiments. Paeonol dose-dependently enhanced the
      formation of acidic vesicular organelles and autophagosmomes, up-regulated the
      expression of LC3II and increased p62 degradation. The autophagy inhibitor CQ
      obviously attenuated Paeonol-induced autophagy and the anti-proliferation effect
      in VSMCs. In addition, Paeonol induced phosphorylation of AMPK and reduced
      phosphorylation of mTOR. An AMPK inhibitor reversed the Paeonol-induced p
      mTOR/mTOR decrease. Paeonol induced LC3II conversion, increased p62 degradation
      and inhibited cell proliferation in VSMCs, the effects of which were abolished by
      si-AMPK. Conclusion: These results imply that Paeonol inhibits proliferation of
      VSMCs by up-regulating autophagy, and activating the AMPK/mTOR signaling pathway,
      providing new insights into the anti-atherosclerosis activity of Paeonol.

PMID- 29354056
TI  - Rimonabant Kills Colon Cancer Stem Cells without Inducing Toxicity in Normal
      Colon Organoids.
AB  - Colorectal cancer (CRC), like other tumor types, is a highly heterogeneous
      disease. Within the tumor bulk, intra-tumoral heterogeneity is also ascribable to
      Cancer Stem Cells (CSCs) subpopulation, characterized by high chemoresistance and
      the unique ability to retain tumorigenic potential, thus associated to tumor
      recurrence. High dynamic plasticity of CSCs, makes the development of winning
      therapeutic strategies even more complex to completely eradicate tumor fuel.
      Rimonabant, originally synthesized as antagonist/inverse agonist of Cannabinoid
      Receptor 1, is able to inactivate Wnt signaling, both in vitro and in vivo, in
      CRC models, through inhibition of p300-histone acetyltransferase activity. Since
      Wnt/beta-Catenin pathway is the main player underlying CSCs dynamic, this finding
      candidates Rimonabant as potential modulator of cancer stemness, in CRC. In this
      work, using established 3D cultures of primary colon CSCs, taking into account
      the tumor heterogeneity through monitoring of Wnt activity, we demonstrated that
      Rimonabant was able to reduces both tumor differentiated cells and colon CSCs
      proliferation and to control their survival in long term cultures. Interestingly,
      in ex vivo model of wild type human organoids, retaining both architecture and
      heterogeneity of original tissue, Rimonabant showed no toxicity against cells
      from healthy colon epithelium, suggesting its potential selectivity toward cancer
      cells. Overall, results from this work provided new insights on anti-tumor
      efficacy of Rimonabant, strongly suggesting that it could be a novel lead
      compound for CRC treatment.

PMID- 29354057
TI  - miR449a/SIRT1/PGC-1alpha Is Necessary for Mitochondrial Biogenesis Induced by T-2
      Toxin.
AB  - T-2 toxin is one of the type A trichothecenes produced mainly by the Fusarium
      genus. Due to its broad distribution and highly toxic nature, it is of great
      concern as a threat to human health and animal breeding. In addition to its
      ribotoxic effects, T-2 toxin exposure leads to mitochondrial dysfunction,
      reactive oxygen species (ROS) accumulation and eventually cell apoptosis. We
      observed that mitochondrial biogenesis is highly activated in animal cells
      exposed to T-2 toxin, probably in response to the short-term toxic effects of T-2
      toxin. However, the molecular mechanisms of T-2 toxin-induced mitochondrial
      biogenesis remain unclear. In this study, we investigated the regulatory
      mechanism of key factors in the ROS production and mitochondrial biogenesis that
      were elicited by T-2 toxin in HepG2 and HEK293T cells. Low dosages of T-2 toxin
      significantly increased the levels of both mitochondrial biogenesis and ROS. This
      increase was linked to the upregulation of SIRT1, which is controlled by miR
      449a, whose expression was strongly inhibited by T-2 toxin treatment. In
      addition, we found that T-2 toxin-induced mitochondrial biogenesis resulted from
      SIRT1-dependent PGC-1alpha deacetylation. The accumulation of PGC-1alpha
      deacetylation, mediated by high SIRT1 levels in T-2 toxin-treated cells,
      activated the expression of many genes involved in mitochondrial biogenesis.
      Together, these data indicated that the miR449a/SIRT1/deacetylated PGC-1alpha
      axis plays an essential role in the ability of moderate concentrations of T-2
      toxin to stimulate mitochondrial biogenesis and ROS production.

PMID- 29354058
TI  - SCD1 Confers Temozolomide Resistance to Human Glioma Cells via the
      Akt/GSK3beta/beta-Catenin Signaling Axis.
AB  - Resistance to temozolomide (TMZ), the standard chemotherapy agent for
      glioblastoma (GBM), poses a major clinical challenge to GBM prognosis.
      Understanding the mechanisms of TMZ resistance can help to identify novel drug
      targets and more effective therapies. Recent studies suggest that bioenergetic
      alterations of cancer cells play important roles in drug resistance. In our
      study, the altered metabolism of cancer cells was observed using a metabolic PCR
      array. We found that stearoyl-coenzyme A desaturase 1 (SCD1), a key rate-limiting
      enzyme for synthesis of monounsaturated fatty acids, was significantly
      upregulated in TMZ-resistant GBM cells compared to their parental counterparts.
      Overexpression of SCD1 promoted resistance to TMZ in parental GBM cells, whereas
      SCD1 downregulation by siRNA could re-sensitize TMZ-resistant cells in vitro.
      Combinational treatment of TMZ and an SCD1-specific inhibitor showed a combined
      inhibitory effect on TMZ-resistant glioma cells. We also observed that
      overexpression of SCD1 promoted Akt/GSK3beta/beta-catenin signaling, while
      silencing of SCD1 inhibited the signaling. The combination of an Akt activator
      with exogenous SCD1 or the combined inhibition of Akt and enforced expression of
      SCD1 resulted in the most significant changes of Akt signaling. Functionally,
      significantly lower viability and mobility rates were observed in TMZ-resistant
      cells when treated with Akt inhibitors and an SCD1 inhibitor simultaneously
      compared to when treated individually. In conclusion, our study identified SCD1
      along with its functional pathway as a novel target in the development of TMZ
      resistance. SCD1 inhibition used alone or in combination with Akt inhibition
      could effectively overcome TMZ resistance in gliomas.

PMID- 29354059
TI  - International Clinical Trials in Latin American and Caribbean Countries: Research
      and Development to Meet Local Health Needs.
AB  - Introduction: Although international health research involves some benefits for
      the host countries, such as access to innovative treatments, the research itself
      may not be aligned with their communities' actual health needs. Objective: To map
      the global landscape of clinical trials run in Latin American and Caribbean
      countries and discuss the addressing of local health needs in the agenda of
      international clinical trials. Methods: The present study is a cross-sectional
      overview and used data referent to studies registered between 01/01/2014 and
      12/31/2014 in the World Health Organization's (WHO) International Clinical Trials
      Registry Platform (ICTRP). Results: Non-communicable diseases such as diabetes,
      cancer, and asthma-studies which were financed mainly by industries-were the
      conditions investigated most in the region of Latin America and the Caribbean.
      The neglected diseases, on the other hand, such as Chagas disease, and dengue,
      made up 1% of the total number of studies. Hospitals and nonprofit
      nongovernmental organizations prioritize resources for investigating new drugs
      for neglected diseases, such as Chagas disease and dengue. Conclusion: The
      international multicenter clinical trials for investigating new drugs are aligned
      with the health needs of the region of Latin America and the Caribbean, when one
      considers the burden resulting from the non-communicable diseases in this region.
      However, the transmissible diseases, such as tuberculosis and AIDS, and the
      neglected diseases, such as Chagas disease and dengue, which have an important
      impact on public health in this region, continue to arouse little interest among
      the institutions which finance the clinical trials.

PMID- 29354061
TI  - Toxicity Evaluation of Graphene Oxide and Titania Loaded Nafion Membranes in
      Zebrafish.
AB  - The use of nanomaterials in several application fields has received in the last
      decades a great attention due to their peculiar properties, but also raised many
      doubts about possible toxicity when these materials are used for some specific
      applications, such as water purification. Indeed a careful investigation is
      needed in order to exclude possible harmful side effects related to the use of
      nanotechnology. Nanoparticles effects on the marine organisms may depend on their
      chemical composition, size, surface structure, solubility, shape and how the
      individual nanoparticles aggregate together. In order to make the most of their
      potential, without polluting the environment, many researchers are trying to trap
      them into some kind of matrix that keeps them active but avoids their dispersion
      in the environment. In this study we have tested nanocomposite membranes prepared
      using Nafion polymer combined with various fillers, such as anatase-type TiO2
      nanoparticles and graphene oxide. The non-toxicity of these nanocomposites,
      already shown to be effective for water purification applications in our previous
      studies, was recognized by testing the effect of the different materials on
      zebrafish embryos. Zebrafish was considered an excellent model for
      ecotoxicological studies and for this motivation zebrafish embryos were exposed
      to different concentrations of free nanoparticles and to the nanocomposite
      membranes. As biomarkers of exposure, we evaluated the expression of heme
      oxygenase 1 and inducible Nitric Oxide Synthases by immunohistochemistry and gene
      expression. Embryo toxicity test showed that nor sublethal effects neither
      mortality were caused by the different nanoparticles and nano-systems tested.
      Only zebrafish larvae exposed to free nanoparticles have shown a different
      response to antibodies anti-heme-oxygenase 1 and anti- inducible Nitric Oxide
      Synthases. The immunolocalization analysis in fact has highlighted an increase in
      the synthesis of these biomarkers.

PMID- 29354060
TI  - Interpreting Signal Amplitudes in Surface Electromyography Studies in Sport and
      Rehabilitation Sciences.
AB  - Surface electromyography (sEMG) is a popular research tool in sport and
      rehabilitation sciences. Common study designs include the comparison of sEMG
      amplitudes collected from different muscles as participants perform various
      exercises and techniques under different loads. Based on such comparisons,
      researchers attempt to draw conclusions concerning the neuro- and
      electrophysiological underpinning of force production and hypothesize about
      possible longitudinal adaptations, such as strength and hypertrophy. However,
      such conclusions are frequently unsubstantiated and unwarranted. Hence, the goal
      of this review is to discuss what can and cannot be inferred from comparative
      research designs as it pertains to both the acute and longitudinal outcomes.
      General methodological recommendations are made, gaps in the literature are
      identified, and lines for future research to help improve the applicability of
      sEMG are suggested.

PMID- 29354062
TI  - Support Vector Machine Based Monitoring of Cardio-Cerebrovascular Reserve during
      Simulated Hemorrhage.
AB  - Introduction: In the initial phase of hypovolemic shock, mean blood pressure (BP)
      is maintained by sympathetically mediated vasoconstriction rendering BP
      monitoring insensitive to detect blood loss early. Late detection can result in
      reduced tissue oxygenation and eventually cellular death. We hypothesized that a
      machine learning algorithm that interprets currently used and new hemodynamic
      parameters could facilitate in the detection of impending hypovolemic shock.
      Method: In 42 (27 female) young [mean (sd): 24 (4) years], healthy subjects
      central blood volume (CBV) was progressively reduced by application of -50 mmHg
      lower body negative pressure until the onset of pre-syncope. A support vector
      machine was trained to classify samples into normovolemia (class 0), initial
      phase of CBV reduction (class 1) or advanced CBV reduction (class 2). Nine models
      making use of different features were computed to compare sensitivity and
      specificity of different non-invasive hemodynamic derived signals. Model features
      included: volumetric hemodynamic parameters (stroke volume and cardiac output),
      BP curve dynamics, near-infrared spectroscopy determined cortical brain
      oxygenation, end-tidal carbon dioxide pressure, thoracic bio-impedance, and
      middle cerebral artery transcranial Doppler (TCD) blood flow velocity. Model
      performance was tested by quantifying the predictions with three methods:
      sensitivity and specificity, absolute error, and quantification of the log odds
      ratio of class 2 vs. class 0 probability estimates. Results: The combination with
      maximal sensitivity and specificity for classes 1 and 2 was found for the model
      comprising volumetric features (class 1: 0.73-0.98 and class 2: 0.56-0.96).
      Overall lowest model error was found for the models comprising TCD curve
      hemodynamics. Using probability estimates the best combination of sensitivity for
      class 1 (0.67) and specificity (0.87) was found for the model that contained the
      TCD cerebral blood flow velocity derived pulse height. The highest combination
      for class 2 was found for the model with the volumetric features (0.72 and 0.91).
      Conclusion: The most sensitive models for the detection of advanced CBV reduction
      comprised data that describe features from volumetric parameters and from
      cerebral blood flow velocity hemodynamics. In a validated model of hemorrhage in
      humans these parameters provide the best indication of the progression of central
      hypovolemia.

PMID- 29354063
TI  - Physiological Responses and Ovarian Development of Female Chinese Mitten Crab
      Eriocheir sinensis Subjected to Different Salinity Conditions.
AB  - Salinity plays a key role affecting ovarian development, osmoregulation and
      metabolism of female Chinese mitten crab, Eriocheir sinensis during reproductive
      migration. In this study, female E. sinensis after their puberty molt were
      subjected to four salinities of 0, 6, 12, and 180/00 for 40 days to investigate
      the salinity effects on their ovarian development as well as a range of important
      physiological parameters. Elevated salinity accelerated the ovarian development
      with ovigerous crabs found at salinity treatments of 12 and 180/00 despite no
      copulation had occurred. Meanwhile the survival rate of female crabs showed a
      decreasing trend with increasing salinity. Higher salinity also led to increased
      hemolymph Na+, K+, Ca2+, Cl-, and Mg2+ concentrations. The 60/00 treatment had
      the highest contents of hemolymph total and major free amino acids while the
      Na+/K+ -ATPase activity in the posterior gills was the lowest among treatments.
      Total n-3 polyunsaturated fatty acids (?n-3PUFA) and n-3/n-6 PUFA ratio in the
      anterior gills showed a decreasing trend with salinity while 180/00 had the
      highest ?PUFA and ?n-6PUFA. The ?n-3PUFA content and n-3/n-6 PUFA ratio of the
      posterior gills showed a fluctuating pattern and the highest value was detected
      at 00/00, while an increasing trend was found for the ?n-6PUFA with increasing
      salinity. The hemolymph glucose showed a decreasing trend with increasing
      salinity and the highest total cholesterol in hemolymph was detected at 120/00.
      The 180/00 treatment had the highest levels of hemolymph gamma
      glutamyltransferase, alkaline phosphatase and acid phosphatase, as well as
      glucose, urea and acid phosphatase in hepatopancreas while the highest hemolymph
      superoxide dismutase and malondialdehyde were detected at 00/00. Overall, the
      results showed that salinity increase from freshwater to brackish conditions led
      to lower metabolism, accelerated ovarian development, and the appearance of
      ovigerous crabs without copulation in female E. sinensis post puberty molt.

PMID- 29354065
TI  - The Effect of Tai Chi on Cardiorespiratory Fitness for Coronary Disease
      Rehabilitation: A Systematic Review and Meta-Analysis.
AB  - Background: Tai Chi that originated in China as a martial art is an aerobic
      exercise with low-to-moderate intensity and may play a role in cardiac
      rehabilitation. Aim: To systematically review the effect of Tai Chi on
      cardiorespiratory fitness for coronary disease rehabilitation. Methods: We
      performed a search for Chinese and English studies in the following databases:
      PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese
      Biomedical Literature Database, China Knowledge Resource Integrated Database,
      Wanfang Data, and China Science and Technology Journal Database. The search
      strategy included terms relating to or describing Tai Chi and coronary disease,
      and there were no exclusion criteria for other types of diseases or disorders.
      Further, bibliographies of the related published systematic reviews were also
      reviewed. The searches, data extraction, and risk of bias (ROB) assessments were
      conducted by two independent investigators. Differences were resolved by
      consensus. RevMan 5.3.0 was used to analyze the study results. We used
      quantitative synthesis if the included studies were sufficiently homogeneous and
      performed subgroup analyses for studies with different control groups. To
      minimize bias in our findings, we used GRADEpro to grade the available evidence.
      Results: Five studies were enrolled-two randomized controlled trials (RCTs) and
      three nonrandomized controlled trials (N-RCTs)-that included 291 patients. All
      patients had coronary disease. ROB assessments showed a relatively high selection
      and detection bias. Meta-analyses showed that compared to other types of low- or
      moderate-intensity exercise, Tai Chi could significantly improve VO2max [MD =
      4.71, 95% CI (3.58, 5.84), P < 0.00001], but it seemed less effective at
      improving VO2max as compared to high-intensity exercise. This difference,
      however, was not statistically significant [MD = -1.10, 95% CI (-2.46, 0.26), P =
      0.11]. The GRADEpro showed a low level of the available evidence. Conclusion:
      Compared to no exercise or other types of exercise with low-to-moderate
      intensity, Tai Chi seems a good choice for coronary disease rehabilitation in
      improving cardiorespiratory fitness. However, owing to the poor methodology
      quality, more clinical trials with large sample size, strict randomization, and
      clear description about detection and reporting processes are needed to further
      verify the evidence.

PMID- 29354064
TI  - JNK1 Mediates Lipopolysaccharide-Induced CD14 and SR-AI Expression and Macrophage
      Foam Cell Formation.
AB  - Foam cell formation is the key process in the development of atherosclerosis. The
      uptake of oxidized low-density lipoprotein (oxLDL) converts macrophages into foam
      cells. We recently reported that lipopolysaccharide (LPS)-induced foam cell
      formation is regulated by CD14 and scavenger receptor AI (SR-AI). In this study,
      we employed pharmaceutical and gene knockdown approaches to determine the
      upstream molecular mediators, which control LPS-induced foam cell formation. Our
      results demonstrated that the specific c-Jun N-terminal kinase (JNK) pathway
      inhibitor, SP600125, but neither the specific inhibitor of extracellular
      signaling-regulated kinase (ERK) kinase MEK1/2, U0126, nor the specific inhibitor
      of p38 MAPK, SB203580, significantly blocks LPS-induced oxLDL uptake, suggesting
      that the JNK pathway is the upstream mediator of LPS-induced oxLDL uptake/foam
      cell formation. To address whether JNK pathway mediates LPS-induced oxLDL uptake
      is due to JNK pathway-regulated CD14 and SR-AI expression, we assessed whether
      the pharmaceutical inhibitor of JNK influences LPS-induced expression of CD14 and
      SR-AI. Our results indicate that JNK pathway mediates LPS-induced CD14 and SR-AI
      expression. To conclusively address the isoform role of JNK family, we depleted
      JNK isoforms using the JNK isoform-specific siRNA. Our data showed that the
      depletion of JNK1, but not JNK2 blocked LPS-induced CD14/SR-AI expression and
      foam cell formation. Taken together, our results reveal for the first time that
      JNK1 is the key mediator of LPS-induced CD14 and SR-AI expression in macrophages,
      leading to LPS-induced oxLDL uptake/foam cell formation. We conclude that the
      novel JNK1/CD14/SR-AI pathway controls macrophage oxLDL uptake/foam cell
      formation.

PMID- 29354066
TI  - Identification of Basic Fibroblast Growth Factor as the Dominant Protector of
      Laminar Shear Medium from the Modified Shear Device in Tumor Necrosis Factor
      alpha Induced Endothelial Dysfunction.
AB  - Background and Aims: Endothelial dysfunction is a hallmark of cardiovascular
      diseases. The straight region of an artery is protected from atherosclerosis via
      its laminar blood flow and high shear stress. This study investigated the
      cytoprotective effects of a new laminar shear medium (LSM) derived from a
      modified cone-and-plate shear device and identified basic fibroblast growth
      factor (bFGF) secreted by human aortic endothelial cells (HAECs) as the dominant
      protective factor in the LSM. Methods: Based on a modified cone-and-plate shear
      device system, HAECs were exposed to laminar shear (15 dynes/cm2) and static
      control for 24 h to produce a new supernatant LSM and static medium (SM).
      Evaluation of the protective effects of LSM and SM on endothelial dysfunction
      induced by tumor necrosis factor (TNF)-alpha (10 ng/mL), which leads to
      production of reactive oxygen species (ROS), inflammatory monocyte adhesion, and
      tissue factor activity. ROS induction-, inflammation-, and thrombosis-related
      genes and protein expression were evaluated by quantitative-PCR and western
      blotting. To identify the cytokines that played a key role in the cytoprotective
      action of the LSM, we used cytokine antibody arrays, selected an abundant marker
      cytokine, bFGF, and validated the different cytoprotective effects of recombinant
      bFGF (rbFGF) and neutralization by monoclonal antibody (rbFGF+Ab) co-treatment.
      Aortic and lung tissues from different groups of C57BL/6J mice were examined by
      immunohistochemistry. SB203580 (specific inhibitor of p38) and BIX02189 (specific
      inhibitor of MEK5) were used to identify bFGF as the main cytoprotective factor
      acting via p38/MAPK and MEK5-KLF2 pathways. Results: Compared with traditional
      LSM, the new LSM not only significantly decreased TNF-alpha-induced intracellular
      adhesion molecule 1 and plasminogen activator inhibitor type 1 gene expression,
      but also significantly increased heme oxygenase 1 gene expression. The new LSM
      and bFGF attenuated TNF-alpha-induced ROS induction, inflammation, and tissue
      factor activity and inhibited the inflammatory- and thrombosis-related
      gene/protein overexpression both in vitro and in vivo. Mechanistically, the
      cytoprotective action of bFGF was mediated via the p38/MAPK and MEK5-KLF2
      pathways. Conclusion: bFGF was identified as the critical factor mediating the
      cytoprotective effects of LSM derived from the modified laminar shear system.

PMID- 29354067
TI  - Composite Biomarkers Derived from Micro-Electrode Array Measurements and Computer
      Simulations Improve the Classification of Drug-Induced Channel Block.
AB  - The Micro-Electrode Array (MEA) device enables high-throughput electrophysiology
      measurements that are less labor-intensive than patch-clamp based techniques.
      Combined with human-induced pluripotent stem cells cardiomyocytes (hiPSC-CM), it
      represents a new and promising paradigm for automated and accurate in vitro drug
      safety evaluation. In this article, the following question is addressed: which
      features of the MEA signals should be measured to better classify the effects of
      drugs? A framework for the classification of drugs using MEA measurements is
      proposed. The classification is based on the ion channels blockades induced by
      the drugs. It relies on an in silico electrophysiology model of the MEA, a
      feature selection algorithm and automatic classification tools. An in silico
      model of the MEA is developed and is used to generate synthetic measurements. An
      algorithm that extracts MEA measurements features designed to perform well in a
      classification context is described. These features are called composite
      biomarkers. A state-of-the-art machine learning program is used to carry out the
      classification of drugs using experimental MEA measurements. The experiments are
      carried out using five different drugs: mexiletine, flecainide, diltiazem,
      moxifloxacin, and dofetilide. We show that the composite biomarkers outperform
      the classical ones in different classification scenarios. We show that using both
      synthetic and experimental MEA measurements improves the robustness of the
      composite biomarkers and that the classification scores are increased.

PMID- 29354068
TI  - Developing a Three-Dimensional (3D) Assessment Method for Clubfoot-A Study
      Protocol.
AB  - Background: Congenital talipes equinovarus (CTEV) or clubfoot is a common
      pediatric congenital foot deformity that occurs 1 in 1,000 live births. Clubfoot
      is characterized by four types of foot deformities: hindfoot equinus; midfoot
      cavus; forefoot adductus; and hindfoot varus. A structured assessment method for
      clubfoot is essential for quantifying the initial severity of clubfoot deformity
      and recording the progress of clubfoot intervention. Aim: This study aims to
      develop a three-dimensional (3D) assessment method to evaluate the initial
      severity of the clubfoot and monitor the structural changes of the clubfoot after
      each casting intervention. In addition, this study explores the relationship
      between the thermophysiological changes in the clubfoot at each stage of the
      casting intervention and in the normal foot. Methods: In this study, a total of
      10 clubfoot children who are <2 years old will be recruited. Also, the data of
      the unaffected feet of a total of 10 children with unilateral clubfoot will be
      obtained as a reference for normal feet. A Kinect 3D scanner will be used to
      collect the 3D images of the clubfoot and normal foot, and an Infrared
      thermography camera (IRT camera) will be used to collect the thermal images of
      the clubfoot. Three-dimensional scanning and IR imaging will be performed on the
      foot once a week before casting. In total, 6-8 scanning sessions will be
      performed for each child participant. The following parameters will be calculated
      as outcome measures to predict, monitor, and quantify the severity of the
      clubfoot: Angles cross section parameters, such as length, width, and the radial
      distance; distance between selected anatomical landmarks, and skin temperature of
      the clubfoot and normal foot. The skin temperature will be collected on selected
      areas (forefoot, mid foot, and hindfoot) to find out the relationship between the
      thermophysiological changes in the clubfoot at each stage of the casting
      treatment and in the normal foot. Ethics: The study has been reviewed and
      approved on 17 August 2016 by the Sydney Children's Hospitals Network Human
      Research Ethics Committee (SCHN HREC), Sydney, Australia. The Human Research
      Ethics Committee (HREC) registration number for this study is: HREC/16/SCHN/163.

PMID- 29354069
TI  - Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target
      Discovery and Safety Pharmacology Testing.
AB  - Dynamic clamp, a hybrid-computational-experimental technique that has been used
      to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging
      as a promising tool in the discovery of potential anti-arrhythmic targets and in
      pharmacological safety testing. Through the injection of computationally
      simulated conductances into isolated cardiomyocytes in a real-time continuous
      loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside
      traditional static voltage and current protocols. Recent applications include
      fine manipulation of injected artificial conductances to identify promising drug
      targets in the prevention of arrhythmia and the direct testing of model-based
      hypotheses. Furthermore, dynamic clamp has been used to enhance existing
      experimental models by addressing their intrinsic limitations, which increased
      predictive power in identifying pro-arrhythmic pharmacological compounds. Here,
      we review the recent advances of the dynamic clamp technique in cardiac
      electrophysiology with a focus on its future role in the development of safety
      testing and discovery of anti-arrhythmic drugs.

PMID- 29354070
TI  - Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect.
AB  - Carbonic anhydrase II (CAII) is expressed along the nephron where it interacts
      with a number of transport proteins augmenting their activity. Aquaporin-1 (AQP1)
      interacts with CAII to increase water flux through the water channel. Both CAII
      and aquaporin-1 are expressed in the thin descending limb (TDL); however, the
      physiological role of a CAII-AQP1 interaction in this nephron segment is not
      known. To determine if CAII was required for urinary concentration, we studied
      water handling in CAII-deficient mice. CAII-deficient mice demonstrate polyuria
      and polydipsia as well as an alkaline urine and bicarbonaturia, consistent with a
      type III renal tubular acidosis. Natriuresis and hypercalciuria cause polyuria,
      however, CAII-deficient mice did not have increased urinary sodium nor calcium
      excretion. Further examination revealed dilute urine in the CAII-deficient mice.
      Urinary concentration remained reduced in CAII-deficient mice relative to wild
      type animals even after water deprivation. The renal expression and localization
      by light microscopy of NKCC2 and aquaporin-2 was not altered. However, CAII
      deficient mice had increased renal AQP1 expression. CAII associates with and
      increases water flux through aquaporin-1. Water flux through aquaporin-1 in the
      TDL of the loop of Henle is essential to the concentration of urine, as this is
      required to generate a concentrated medullary interstitium. We therefore measured
      cortical and medullary interstitial concentration in wild-type and CAII-deficient
      mice. Mice lacking CAII had equivalent cortical interstitial osmolarity to wild
      type mice: however, they had reduced medullary interstitial osmolarity. We
      propose therefore that reduced water flux through aquaporin-1 in the TDL in the
      absence of CAII prevents the generation of a maximally concentrated medullary
      interstitium. This, in turn, limits urinary concentration in CAII deficient mice.

PMID- 29354071
TI  - Action Potential Recording and Pro-arrhythmia Risk Analysis in Human Ventricular
      Trabeculae.
AB  - To assess drug-induced pro-arrhythmic risk, especially Torsades de Pointe (TdP),
      new models have been proposed, such as in-silico modeling of ventricular action
      potential (AP) and stem cell-derived cardiomyocytes (SC-CMs). Previously we
      evaluated the electrophysiological profile of 15 reference drugs in hESC-CMs and
      hiPSC-CMs for their effects on intracellular AP and extracellular field
      potential, respectively. Our findings indicated that SC-CMs exhibited immature
      phenotype and had the propensity to generate false positives in predicting TdP
      risk. To expand our knowledge with mature human cardiac tissues for drug-induced
      pro-arrhythmic risk assessment, human ventricular trabeculae (hVT) from ethically
      consented organ donors were used to evaluate the effects of the same 15 drugs (8
      torsadogenic, 5 non-torsadogenic, and 2 discovery molecules) on AP parameters at
      1 and 2 Hz. Each drug was tested blindly with 4 concentrations in duplicate
      trabeculae from 2 hearts. To identify the pro-arrhythmic risk of each drug, a pro
      arrhythmic score was calculated as the weighted sum of percent drug-induced
      changes compared to baseline in various AP parameters, including AP duration and
      recognized pro-arrhythmia predictors such as triangulation, beat-to-beat
      variability and incidence of early-afterdepolarizations, at each concentration.
      In addition, to understand the translation of this preclinical hVT AP-based model
      to clinical studies, a ratio that relates each testing concentration to the human
      therapeutic unbound Cmax (Cmax) was calculated. At a ratio of 10, for the 8
      torsadogenic drugs, 7 were correctly identified by the pro-arrhythmic score; 1
      was mislabeled. For the 5 non-torsadogenic drugs, 4 were correctly identified as
      safe; 1 was mislabeled. Calculation of sensitivity, specificity, positive
      predictive value, and negative predictive value indicated excellent performance.
      For example, at a ratio of 10, scores for sensitivity, specificity, positive
      predictive value and negative predictive values were 0.88, 0.8, 0.88 and 0.8,
      respectively. Thus, the hVT AP-based model combined with the integrated analysis
      of pro-arrhythmic score can differentiate between torsadogenic and non
      torsadogenic drugs, and has a greater predictive performance when compared to
      human SC-CM models.

PMID- 29354072
TI  - Obesity or Overweight, a Chronic Inflammatory Status in Male Reproductive System,
      Leads to Mice and Human Subfertility.
AB  - Obesity is frequently accompanied with chronic inflammation over the whole body
      and is always associated with symptoms that include those arising from metabolic
      and vascular alterations. On the other hand, the chronic inflammatory status in
      the male genital tract may directly impair spermatogenesis and is even associated
      with male subfertility. However, it is still unclear if the chronic inflammation
      induced by obesity damages spermatogenesis in the male genital tract. To address
      this question, we used a high fat diet (HFD) induced obese mouse model and
      recruited obese patients from the clinic. We detected increased levels of tumor
      necrosis factor (TNF-alpha), interleukin-6 (IL-6), and NOD-like receptor family
      pyrin domain containing-3 (NLRP3) in genital tract tissues including testis,
      epididymis, seminal vesicle, prostate, and serum from obese mice. Meanwhile, the
      levels of immunoglobulin G (IgG) and corticosterone were significantly higher
      than those in the control group in serum. Moreover, signal factors regulated by
      TNF-alpha, i.e., p38, nuclear factor-kappaB (NF-kappaB), Jun N-terminal kinase
      (JNK), extracellular signal-regulated kinase (ERK), and their phosphorylated
      status, and inflammasome protein NLRP3 were expressed at higher levels in the
      testis. For overweight and obese male patients, the increased levels of TNF-alpha
      and IL-6 were also observed in their seminal plasma. Furthermore, there was a
      positive correlation between the TNF-alpha and IL-6 levels and BMI whereas they
      were inversely correlated with the sperm concentration and motility. In
      conclusion, impairment of male fertility may stem from a chronic inflammatory
      status in the male genital tract of obese individuals.

PMID- 29354074
TI  - Voluntary Wheel Running Does Not Alter Mortality to or Immunogenicity of Vaccinia
      Virus in Mice: A Pilot Study.
AB  - Exercise has been shown to improve immune responses to viral infections and
      vaccines in several mouse models. However, previous pathogen studies have
      primarily used infections limited to the respiratory tract. Additionally,
      previous studies have utilized forced treadmill exercise paradigms, and voluntary
      wheel running (VWR) has been shown to have differential effects on the immune
      system in non-infection models. We examined whether VWR could improve morbidity
      and mortality to a 50% lethal dose of vaccinia virus (VACV), a systemic pathogen
      commonly used to examine immune responses. Additionally, we examined whether VWR
      could improve antibody response to a replication-deficient strain of VACV,
      mimicking a vaccination. Male C57Bl/6J mice underwent 8 weeks of VWR or remained
      sedentary, then were infected intranasally with 105 PFU VACV strain WR and
      followed 14 days for weight loss. Mice in the vaccination study ran or were
      sedentary for 8 weeks, then were given 106 PFU of replication-deficient VACV
      strain MVA intraperitoneally. Blood was collected at 1, 2, and 4 weeks post
      inoculation, and anti-VACV IgG titer was determined by ELISA. VWR did not improve
      mortality due to VACV infection (p = 0.26), although fewer VWR mice (4/10) died
      compared to sedentary (SED, 6/10). VWR did not prevent body weight loss due to
      infection compared to SED (p = 0.20), although VWR mice loss slightly less weight
      compared to SED through the first 6 days post-infection. Food intake was
      significantly reduced in SED post-infection compared to VWR (p = 0.05). VWR mice
      developed a greater IgG antibody response, although this was not significant (p =
      0.22). In summary, VWR did not protect against mortality to VACV or prevent
      infection-induced weight loss, and VWR did not enhance antibody responses.
      However, there were non-significant trends toward VWR-related improvements in
      these outcomes, and post-infection food intake was improved by VWR.

PMID- 29354073
TI  - Influence of Maturation Status on Eccentric Exercise-Induced Muscle Damage and
      the Repeated Bout Effect in Females.
AB  - This study compared changes in indirect muscle damage markers, proprioception and
      arterial stiffness after elbow flexor eccentric exercise between pre-pubescent (9
      10 y), pubescent (14-15 y), and post-pubescent (20-24 y) healthy, untrained
      females (n = 13/group). The maturation of the participants was confirmed by the
      hand bone age. All participants performed two bouts of 30 sub-maximal eccentric
      contractions (EC1, EC2) using a dumbbell set at 60% of pre-exercise maximal
      voluntary isometric elbow flexion strength at 90 degrees . Changes in maximal
      voluntary concentric contraction (MVC) torque, muscle soreness (SOR), plasma
      creatine kinase activity, proprioception (position sense, joint reaction angle)
      and arterial stiffness (carotid-femoral pulse-wave velocity: cfPWV) before to 5
      days after EC1 and EC2 were compared among groups by a mixed-design two-way
      ANOVA. Pre-exercise MVC torque and cfPWV were smaller (P < 0.05) for the pre
      pubescent (MVC: 10.0 +/- 0.9 Nm, cfPWV: 903 +/- 60 cm/s) and the pubescent (14.3
      +/- 1.1 Nm, 967 +/- 61 cm/s) than the post-pubescent (19.1 +/- 1.4 Nm, 1,103 +/-
      73 cm/s). Changes in all variables after EC1 were smaller (P < 0.05) for the pre
      pubescent (e.g., MVC at 1 d post-exercise: -10 +/- 6%, peak SOR: 5 +/- 2 mm) than
      the pubescent (-15 +/- 9%, 12 +/- 6 mm) and the post-pubescent (-25 +/- 7%, 19 +/
      13 mm). After EC2, changes in all variables were smaller (P < 0.05) than those
      after EC1 for all groups (e.g., MVC at 1 d post-exercise, pre-pubescent: -4 +/-
      6%, pubescent: -9 +/- 4%, post-pubescent: -14 +/- 5%; peak SOR: 3 +/- 2, 7 +/- 3,
      11 +/- 6 mm), but the magnitude of the repeated bout effect was not different (P
      > 0.05) among the groups. These results show that the extents of muscle damage,
      and proprioception and arterial stiffness changes after eccentric exercise are
      greater at later stages of maturation, but the repeated bout effect is not
      affected by maturation.

PMID- 29354076
TI  - Unable or Unwilling to Exercise Self-control? The Impact of Neuroscience on
      Perceptions of Impulsive Offenders.
AB  - In growing numbers of court cases, neuroscience is presented to document the
      mental state of the offender at the level of the brain. While a small body of
      research has documented the effects of describing the brain state of psychotic
      offenders, this study tested the impact of neuroscience that could apply to far
      more offenders; that is the neuroscience of impulse control. In this online
      vignette experiment, 759 participants sentenced a normally controlled or normally
      impulsive actor, who committed a violent offense on impulse, explained in either
      cognitive or neurobiological terms. Although participants considered the
      neurobiological actor less responsible for his impulsive disposition than the
      cognitive actor, the neuroscientific testimony did not affect attributions of
      choice, blame, dangerousness, or punishment for the criminal act. In fact, the
      neuroscientific testimony exacerbated the perception that the offender offended
      consciously and "really wanted" to offend. The described disposition of the actor
      was also influential: participants attributed more capacity for reform, more free
      choice and consequently, more blame to the normally controlled actor.
      Participants also attributed this actor's offending more to his social life
      experiences and less to his genes and brain. However, this shift in attributions
      was unable to explain the greater blame directed at this offender. Together, such
      findings suggest that even when neuroscience changes attributions for impulsive
      character, attributions for impulsive offending may remain unchanged. Hence this
      study casts doubt on the mitigating and aggravating potential of neuroscientific
      testimony in court.

PMID- 29354077
TI  - Constraints on Tone Sensitivity in Novel Word Learning by Monolingual and
      Bilingual Infants: Tone Properties Are More Influential than Tone Familiarity.
AB  - This study compared tone sensitivity in monolingual and bilingual infants in a
      novel word learning task. Tone language learning infants (Experiment 1, Mandarin
      monolingual; Experiment 2, Mandarin-English bilingual) were tested with Mandarin
      (native) or Thai (non-native) lexical tone pairs which contrasted static vs.
      dynamic (high vs. rising) tones or dynamic vs. dynamic (rising vs. falling)
      tones. Non-tone language, English-learning infants (Experiment 3) were tested on
      English intonational contrasts or the Mandarin or Thai tone contrasts.
      Monolingual Mandarin language infants were able to bind tones to novel words for
      the Mandarin High-Rising contrast, but not for the Mandarin Rising-Falling
      contrast; and they were insensitive to both the High-Rising and the Rising
      Falling tone contrasts in Thai. Bilingual English-Mandarin infants were similar
      to the Mandarin monolinguals in that they were sensitive to the Mandarin High
      Rising contrast and not to the Mandarin Rising-Falling contrast. However, unlike
      the Mandarin monolinguals, they were also sensitive to the High Rising contrast
      in Thai. Monolingual English learning infants were insensitive to all three types
      of contrasts (Mandarin, Thai, English), although they did respond differentially
      to tone-bearing vs. intonation-marked words. Findings suggest that infants'
      sensitivity to tones in word learning contexts depends heavily on tone
      properties, and that this influence is, in some cases, stronger than effects of
      language familiarity. Moreover, bilingual infants demonstrated greater
      phonological flexibility in tone interpretation.

PMID- 29354075
TI  - Early Retirement: A Meta-Analysis of Its Antecedent and Subsequent Correlates.
AB  - Early or voluntary retirement (ER) can be defined as the full exit from an
      organizational job or career path of long duration, decided by individuals of a
      certain age at the mid or late career before mandatory retirement age, with the
      aim of reducing their attachment to work and closing a process of gradual
      psychological disengagement from working life. Given the swinging movements that
      characterize employment policies, the potential effects of ER-both for
      individuals and society-are still controversial. This meta-analysis examined the
      relationships between ER and its antecedent and subsequent correlates. Our review
      of the literature was generated with 151 empirical studies, containing a total
      number of 706,937 participants, with a wide range of sample sizes (from N = 27 to
      N = 127,384 participants) and 380 independent effect sizes (ESs), which included
      171 independent samples. A negligible ES value for antecedent correlates of early
      retirement (family pull, job stress, job satisfaction, and income) was obtained
      (which ranged from r = -0.13 to 0.19), while a fair ES was obtained for workplace
      timing for retirement, organizational pressures, financial security, and poor
      physical and mental health, (ranging from r = 0.28 to 0.25). Regarding ER
      subsequent correlates, poor ESs were obtained, ranging from r = 0.08 to 0.18 for
      the relationships with subsequent correlates, and fair ESs only for social
      engagement (r = -0.25). Examination of the potential moderator variables has been
      conducted. Only a reduced percentage of variability of primary studies has been
      explained by moderators. Although potential moderator factors were examined,
      there are several unknown or not measurable factors which contribute to ER and
      about which there are very little data available. The discussion is aimed to
      offer theoretical and empirical implications suggestion in order to improve
      employee's well-being.

PMID- 29354079
TI  - Integrated, Not Isolated: Defining Typological Proximity in an Integrated
      Multilingual Architecture.
AB  - On the surface, bi- and multilingualism would seem to be an ideal context for
      exploring questions of typological proximity. The obvious intuition is that the
      more closely related two languages are, the easier it should be to implement the
      two languages in one mind. This is the starting point adopted here, but we
      immediately run into the difficulty that the overwhelming majority of cognitive,
      computational, and linguistic research on bi- and multilingualism exhibits a
      monolingual bias (i.e., where monolingual grammars are used as the standard of
      comparison for outputs from bilingual grammars). The primary questions so far
      have focused on how bilinguals balance and switch between their two languages,
      but our perspective on typology leads us to consider the nature of bi- and multi
      lingual systems as a whole. Following an initial proposal from Hsin (2014), we
      conjecture that bilingual grammars are neither isolated, nor (completely)
      conjoined with one another in the bilingual mind, but rather exist as integrated
      source grammars that are further mitigated by a common, combined grammar (Cook,
      2016; Goldrick et al., 2016a,b; Putnam and Klosinski, 2017). Here we conceive
      such a combined grammar in a parallel, distributed, and gradient architecture
      implemented in a shared vector-space model that employs compression through
      routinization and dimensionality reduction. We discuss the emergence of such
      representations and their function in the minds of bilinguals. This architecture
      aims to be consistent with empirical results on bilingual cognition and memory
      representations in computational cognitive architectures.

PMID- 29354078
TI  - Learning to Detect Deception from Evasive Answers and Inconsistencies across
      Repeated Interviews: A Study with Lay Respondents and Police Officers.
AB  - Previous research has shown that inconsistencies across repeated interviews do
      not indicate deception because liars deliberately tend to repeat the same story.
      However, when a strategic interview approach that makes it difficult for liars to
      use the repeat strategy is used, both consistency and evasive answers differ
      significantly between truth tellers and liars, and statistical software (binary
      logistic regression analyses) can reach high classification rates (Masip et al.,
      2016b). Yet, if the interview procedure is to be used in applied settings the
      decision process will be made by humans, not statistical software. To address
      this issue, in the current study, 475 college students (Experiment 1) and 142
      police officers (Experiment 2) were instructed to code and use consistency,
      evasive answers, or a combination or both before judging the veracity of Masip et
      al.'s (2016b) interview transcripts. Accuracy rates were high (60% to over 90%).
      Evasive answers yielded higher rates than consistency, and the combination of
      both these cues produced the highest accuracy rates in identifying both truthful
      and deceptive statements. Uninstructed participants performed fairly well (around
      75% accuracy), apparently because they spontaneously used consistency and evasive
      answers. The pattern of results was the same among students, all officers, and
      veteran officers only, and shows that inconsistencies between interviews and
      evasive answers reveal deception when a strategic interview approach that hinders
      the repeat strategy is used.

PMID- 29354080
TI  - Modeling Music Emotion Judgments Using Machine Learning Methods.
AB  - Emotion judgments and five channels of physiological data were obtained from 60
      participants listening to 60 music excerpts. Various machine learning (ML)
      methods were used to model the emotion judgments inclusive of neural networks,
      linear regression, and random forests. Input for models of perceived emotion
      consisted of audio features extracted from the music recordings. Input for models
      of felt emotion consisted of physiological features extracted from the
      physiological recordings. Models were trained and interpreted with consideration
      of the classic debate in music emotion between cognitivists and emotivists. Our
      models supported a hybrid position wherein emotion judgments were influenced by a
      combination of perceived and felt emotions. In comparing the different ML
      approaches that were used for modeling, we conclude that neural networks were
      optimal, yielding models that were flexible as well as interpretable. Inspection
      of a committee machine, encompassing an ensemble of networks, revealed that
      arousal judgments were predominantly influenced by felt emotion, whereas valence
      judgments were predominantly influenced by perceived emotion.

PMID- 29354081
TI  - Gambling-Related Distortions and Problem Gambling in Adolescents: A Model to
      Explain Mechanisms and Develop Interventions.
AB  - Although a number of gambling preventive initiatives have been realized with
      adolescents, many of them have been developed in absence of a clear and
      explicitly described theoretical model. The present work was aimed to analyze the
      adequacy of a model to explain gambling behavior referring to gambling-related
      cognitive distortions (Study 1), and to verify the effectiveness of a preventive
      intervention developed on the basis of this model (Study 2). Following dual
      process theories on cognitive functioning, in Study 1 we tested a model in which
      mindware gap, i.e., susceptibility to the gambler's fallacy, and contaminated
      mindware, i.e., superstitious thinking, were the antecedents of gambling-related
      cognitive distortions that, in turn, affect gambling frequency and problem
      gambling. Participants were 306 male adolescents (Mage = 17.2 years). A path
      analysis indicated that cognitive distortions have a mediating role in the
      relationship that links probabilistic reasoning fallacy and superstitious
      thinking with problem gambling. Following these findings, in Study 2 we developed
      a school-based intervention aimed to reduce gambling-related cognitive
      distortions acting on the above cited mindware problems. A pre- and post-test
      design - with a 6 months follow-up - was performed with 34 male adolescents (Mage
      = 16.8), randomly assigned to two groups (Training and No Training), and their
      baseline equivalence was verified. A Mixed 2 * 2 ANOVA attested a significant
      Time X Group interaction, indicating a significant reduction of the cognitive
      distortions from pre-test to post-test only in the Training group. The follow-up
      attested to the stability of the training effects and the reduction of gambling
      frequency over time. These findings suggest that prevention strategies should
      address mindware problems, which can be considered as predictors of gambling
      related cognitive distortions.

PMID- 29354083
TI  - Do Lessons in Nature Boost Subsequent Classroom Engagement? Refueling Students in
      Flight.
AB  - Teachers wishing to offer lessons in nature may hold back for fear of leaving
      students keyed up and unable to concentrate in subsequent, indoor lessons. This
      study tested the hypothesis that lessons in nature have positive-not negative
      aftereffects on subsequent classroom engagement. Using carefully matched pairs of
      lessons (one in a relatively natural outdoor setting and one indoors), we
      observed subsequent classroom engagement during an indoor instructional period,
      replicating these comparisons over 10 different topics and weeks in the school
      year, in each of two third grade classrooms. Pairs were roughly balanced in how
      often the outdoor lesson preceded or followed the classroom lesson. Classroom
      engagement was significantly better after lessons in nature than after their
      matched counterparts for four of the five measures developed for this study:
      teacher ratings; third-party tallies of "redirects" (the number of times the
      teacher stopped instruction to direct student attention back onto the task at
      hand); independent, photo-based ratings made blind to condition; and a composite
      index each showed a nature advantage; student ratings did not. This nature
      advantage held across different teachers and held equally over the initial and
      final 5 weeks of lessons. And the magnitude of the advantage was large. In 48 out
      of 100 paired comparisons, the nature lesson was a full standard deviation better
      than its classroom counterpart; in 20 of the 48, the nature lesson was over two
      standard deviations better. The rate of "redirects" was cut almost in half after
      a lesson in nature, allowing teachers to teach for longer periods uninterrupted.
      Because the pairs of lessons were matched on teacher, class (students and
      classroom), topic, teaching style, week of the semester, and time of day, the
      advantage of the nature-based lessons could not be attributed to any of these
      factors. It appears that, far from leaving students too keyed up to concentrate
      afterward, lessons in nature may actually leave students more able to engage in
      the next lesson, even as students are also learning the material at hand. Such
      "refueling in flight" argues for including more lessons in nature in formal
      education.

PMID- 29354082
TI  - The Comprehension of Familiar and Novel Metaphoric Meanings in Schizophrenia: A
      Pilot Study.
AB  - Miscomprehension of nonliteral ("figurative") language like metaphors, proverbs,
      idioms, and ironic expressions by patients with schizophrenia is a phenomenon
      mentioned already in historical psychiatric descriptions. However, it was only
      recently that studies did differentiate between novel and conventional metaphors,
      a factor that is known to influence the difficulty of comprehension in healthy
      subjects. Further, familiarity with stimuli is an important factor for
      comprehension, which was not recommended in utmost previous studies. In this
      study, 23 patients with DSM IV schizophrenia and 19 healthy control subjects
      performed a newly-developed German metaphor comprehension test with three types
      of stimuli: novel metaphors, conventional German metaphors, and meaningless
      statements. During the test procedure, participants indicated familiarity with
      the stimulus and then matched the meaning with one out of four given
      alternatives. Familiarity rankings did not significantly differ between patients
      and control subjects. However, on descriptive level, there was a tendency for
      healthy controls to be more familiar with conventional metaphors than
      schizophrenic patients. Further, comprehension of conventional and novel
      metaphors differed significantly between the groups, with higher performance in
      healthy controls. Considering only those metaphors that had been ranked as
      familiar, patients only revealed significant lower performance opposed to
      controls regarding novel metaphors, while they did not differ in conventional
      metaphors. Taken together, the results indicate that patients with schizophrenia
      might show an altered way of comprehension in novel metaphors, leading to more
      misunderstandings. However, their previously reported impairments in conventional
      metaphors might rather be due to a lack of familiarity with the stimuli-making
      conventional metaphors to novel metaphors in the individual case.

PMID- 29354084
TI  - Detection of Ludic Patterns in Two Triadic Motor Games and Differences in
      Decision Complexity.
AB  - The triad is a particular structure in which an ambivalent social relationship
      takes place. This work is focused on the search of behavioral regularities in the
      practice of motor games in triad, which is a little known field. For the
      detection of behavioral patterns not visible to the naked eye, we use Theme. A
      chasing games model was followed, with rules, and in two different structures (A<
      >B<->C<->A and A -> B -> C -> A) on four class groups (two for each structure),
      for a total of 84, 12, and 13 year old secondary school students, 37 girls (44%)
      and 47 boys (56%). The aim was to examine if the players' behavior, in relation
      to the triad structure, matches with any ludic behavior patterns. An
      observational methodology was applied, with a nomothetic, punctual and
      multidimensional design. The intra and inter-evaluative correlation coefficients
      and the generalizability theory ensured the quality of the data. A mixed
      behavioral role system was used (four criteria and 15 categories), and the
      pattern detection software Theme was applied to detect temporal regularities in
      the order of event occurrences. The results show that time location of motor
      responses in triad games was not random. In the "maze" game we detected more
      complex ludic patterns than the "three fields" game, which might be explained by
      means of structural determinants such as circulation. This research points out
      the decisional complexity in motor games, and it confirms the differences among
      triads from the point of view of motor communication.

PMID- 29354085
TI  - Modulation of Spatial Attentional Allocation by Computer-Based Cognitive Training
      during Lacrosse Shooting Performance.
AB  - It has been reported that repetitive execution of a stimulus-response
      compatibility (SRC) task attenuates the interference effect of a choice reaction
      time task, known as a Simon task. We investigated whether attentional control,
      enhanced by repetitive execution of an SRC task, would reduce the interference
      effect of a Simon task and could be transferred to lacrosse shooting skills,
      increasing the likelihood that players would shoot in the direction opposite to
      the goalie's initial movement. Female lacrosse players who were matched in terms
      of age, handedness score, competitive lacrosse playing experience, and playing
      position, were allocated to the SRC task group (n = 15) or the 2-back training
      group (n = 14). Participants underwent 10 sessions of 180 trials of a computer
      based version of either a Type 2 SRC task or the 2-back task, within four
      consecutive weeks. Eight practice trials were completed prior to the execution of
      each task in every training session, during which feedback was provided to
      confirm accurate mapping between the stimulus and response. Before and after the
      training phase, both the magnitude of the Simon effect and the lacrosse shooting
      performance were assessed. After participating in computer-based cognitive
      training, players did indeed increase the number of shots toward the direction
      opposite to that of the movement of the goalie. In conclusion, these findings
      indicate that computer-based cognitive training is beneficial for improving the
      shooting ability of lacrosse players.

PMID- 29354086
TI  - Further Evidence That N2pc Reflects Target Enhancement Rather Than Distracter
      Suppression.
AB  - The N2-posterior-contralateral (N2pc) component is an index in the domain of
      event-related potentials for exploring the underlying mechanism of visual-spatial
      attention. It has been disputed whether the attentional selection reflected by
      N2pc is primarily due to distracter suppression or target enhancement processes.
      We addressed this controversy by combining the pop-out item and the target
      feature, and instructed participants whether the pop-out item included the target
      feature. Thus, in a visual search task, bilateral visual stimuli including a pop
      out item and three distractors were displayed simultaneously. The pop-out
      detection was analyzed under varying two factors: (a) pop-out item as a target or
      non-target (b) the distractors containing a target feature or non-target feature.
      Although all conditions had a salient effect on behavioral performance, the
      reliable difference of N2pc existed only between the target condition and the non
      target condition. These results provided strong support for the hypothesis of
      target enhancement processes.

PMID- 29354087
TI  - Matching Your Face or Appraising the Situation: Two Paths to Emotional Contagion.
AB  - Emotions are believed to converge both through emotional mimicry and social
      appraisal. The present study compared contagion of anger and happiness. In
      Experiment 1, participants viewed dynamic angry and happy faces, with facial
      electromyography recorded from the zygomaticus major and corrugator supercilii as
      emotional mimicry. Self-reported emotional experiences were analyzed as emotional
      contagion. Experiment 2 manipulated social appraisal as the gaze of expression
      toward the target. The results showed that there was emotional contagion for
      angry and happy expressions both in Experiment 1 and Experiment 2. Experiment 1
      indicated an overt mimicry pattern for happy faces, but not for angry faces.
      Experiment 2 found an influence of social appraisal on angry contagion but not on
      happy diffusion. The two experiments suggest that the underlying processes of
      emotional mimicry and social appraisal are differentially relevant for different
      emotional contagion, with happiness processing following a mimicry-based path to
      emotional contagion, and anger processing requiring social appraisal.

PMID- 29354088
TI  - A Framework to Assess Where and How Children Connect to Nature.
AB  - The design of the green infrastructure in urban areas largely ignores how
      people's relation to nature, or human-nature connection (HNC), can be nurtured.
      One practical reason for this is the lack of a framework to guide the assessment
      of where people, and more importantly children, experience significant nature
      situations and establish nature routines. This paper develops such a framework.
      We employed a mixed-method approach to understand what qualities of nature
      situations connect children to nature (RQ1), what constitutes children's HNC
      (RQ2), and how significant nature situations and children's HNC relate to each
      other over time (RQ3). We first interviewed professionals in the field of
      connecting children to nature (N = 26), performed inductive thematic analysis of
      these interviews, and then further examined the inductive findings by surveying
      specialists (N = 275). We identified 16 qualities of significant nature
      situations (e.g., "awe," "engagement of senses," "involvement of mentors") and 10
      abilities that constitute children's HNC (e.g., "feeling comfortable in natural
      spaces," "feeling attached to natural spaces," "taking care of nature"). We
      elaborated three principles to answer our research questions: (1) significant
      nature situations are various and with differing consequences for children's HNC;
      (2) children's HNC is a complex embodied ability; (3) children's HNC progresses
      over time through diverse nature routines. Together, these findings form the
      Assessment framework for Children's Human Nature Situations (ACHUNAS). ACHUNAS is
      a comprehensive framework that outlines what to quantify or qualify when
      assessing "child-nature connecting" environments. It guides the assessment of
      where and how children connect to nature, stimulating both the design of nature
      connecting human habitats as well as pedagogical approaches to HNC.

PMID- 29354089
TI  - Expectation-Maximization-Maximization: A Feasible MLE Algorithm for the Three
      Parameter Logistic Model Based on a Mixture Modeling Reformulation.
AB  - Stable maximum likelihood estimation (MLE) of item parameters in 3PLM with a
      modest sample size remains a challenge. The current study presents a mixture
      modeling approach to 3PLM based on which a feasible Expectation-Maximization
      Maximization (EMM) MLE algorithm is proposed. The simulation study indicates that
      EMM is comparable to the Bayesian EM in terms of bias and RMSE. EMM also produces
      smaller standard errors (SEs) than MMLE/EM. In order to further demonstrate the
      feasibility, the method has also been applied to two real-world data sets. The
      point estimates in EMM are close to those from the commercial programs, BILOG-MG
      and flexMIRT, but the SEs are smaller.

PMID- 29354090
TI  - Fatigue and Sleep in Multiple Sclerosis Patients: A Comparison of Self-Report and
      Performance-Based Measures.
AB  - Background: Multiple sclerosis (MS) patients suffer very often from MS fatigue
      and sleep problems. Despite the detrimental impact on the activities of daily
      living, a short and objective quantification of fatigue and sleep problems is
      currently lacking. Objective: The objective of the study was to systematically
      investigate tonic, intrinsic, and phasic alertness and the relationship of these
      performance-based measures with self-report measures of fatigue and quality of
      sleep. Methods: Thirty-three MS patients without (MS-) and 26 with selected
      comorbid disorders (MS+) and 43 healthy controls (HCs) performed the
      pupillographic sleepiness test (measuring tonic alertness) and the alertness
      subtest of the Test of Attentional Performance (measuring intrinsic and phasic
      alertness). Results: Self-reported and performance-based measures revealed poorer
      performance for both MS groups compared to HC. MS+ patients presented higher
      rates of MS fatigue, sleep problems and depressive symptoms but similar alertness
      scores compared to MS- patients. However, tonic alertness was only higher in MS-
      patients compared to HC. Intrinsic and phasic alertness correlated moderately
      with fatigue ratings. Conclusion: In the diagnostic process of MS fatigue and
      quality of sleep comorbid disorders (depression, anemia, thyroid dysfunction) and
      performance-based measures such as alertness should be considered in daily
      clinical practice.

PMID- 29354091
TI  - Electroencephalogram-Electromyography Coupling Analysis in Stroke Based on
      Symbolic Transfer Entropy.
AB  - The coupling strength between electroencephalogram (EEG) and electromyography
      (EMG) signals during motion control reflects the interaction between the cerebral
      motor cortex and muscles. Therefore, neuromuscular coupling characterization is
      instructive in assessing motor function. In this study, to overcome the
      limitation of losing the characteristics of signals in conventional time series
      symbolization methods, a variable scale symbolic transfer entropy (VS-STE)
      analysis approach was proposed for corticomuscular coupling evaluation. Post
      stroke patients (n = 5) and healthy volunteers (n = 7) were recruited and
      participated in various tasks (left and right hand gripping, elbow bending). The
      proposed VS-STE was employed to evaluate the corticomuscular coupling strength
      between the EEG signal measured from the motor cortex and EMG signal measured
      from the upper limb in both the time-domain and frequency-domain. Results showed
      a greater strength of the bi-directional (EEG-to-EMG and EMG-to-EEG) VS-STE in
      post-stroke patients compared to healthy controls. In addition, the strongest EEG
      EMG coupling strength was observed in the beta frequency band (15-35 Hz) during
      the upper limb movement. The predefined coupling strength of EMG-to-EEG in the
      affected side of the patient was larger than that of EEG-to-EMG. In conclusion,
      the results suggested that the corticomuscular coupling is bi-directional, and
      the proposed VS-STE can be used to quantitatively characterize the non-linear
      synchronization characteristics and information interaction between the primary
      motor cortex and muscles.

PMID- 29354092
TI  - Action Observation Plus Sonification. A Novel Therapeutic Protocol for
      Parkinson's Patient with Freezing of Gait.
AB  - Freezing of gait (FoG) is a disabling symptom associated with falls, with little
      or no responsiveness to pharmacological treatment. Current protocols used for
      rehabilitation are based on the use of external sensory cues. However, cued
      strategies might generate an important dependence on the environment. Teaching
      motor strategies without cues [i.e., action observation (AO) plus Sonification]
      could represent an alternative/innovative approach to rehabilitation that matters
      most on appropriate allocation of attention and lightening cognitive load. We
      aimed to test the effects of a novel experimental protocol to treat patients with
      Parkinson's disease (PD) and FoG, using functional, and clinical scales. The
      experimental protocol was based on AO plus Sonification. 12 patients were treated
      with 8 motor gestures. They watched eight videos showing an actor performing the
      same eight gestures, and then tried to repeat each gesture. Each video was
      composed by images and sounds of the gestures. By means of the Sonification
      technique, the sounds of gestures were obtained by transforming kinematic data
      (velocity) recorded during gesture execution, into pitch variations. The same 8
      motor gestures were also used in a second group of 10 patients; which were
      treated with a standard protocol based on a common sensory stimulation method.
      All patients were tested with functional and clinical scales before, after, at 1
      month, and 3 months after the treatment. Data showed that the experimental
      protocol have positive effects on functional and clinical tests. In comparison
      with the baseline evaluations, significant performance improvements were seen in
      the NFOG questionnaire, and the UPDRS (parts II and III). Importantly, all these
      improvements were consistently observed at the end, 1 month, and 3 months after
      treatment. No improvement effects were found in the group of patients treated
      with the standard protocol. These data suggest that a multisensory approach based
      on AO plus Sonification, with the two stimuli semantically related, could help PD
      patients with FoG to relearn gait movements, to reduce freezing episodes, and
      that these effects could be prolonged over time.

PMID- 29354093
TI  - Kisspeptin/Kisspeptin Receptor System in the Ovary.
AB  - Kisspeptins are a family of neuropeptides that are critical for initiating
      puberty and regulating ovulation in sexually mature females via the central
      control of the hypothalamic-pituitary-gonadal axis. Recent studies have shown
      that kisspeptin and its receptor kisspeptin receptor (KISS1R) are expressed in
      the mammalian ovary. Convincing evidence indicates that kisspeptins can activate
      a wide variety of signals via its binding to KISS1R. Experimental data gathered
      recently suggest a putative role of kisspeptin signaling in the direct control of
      ovarian function, including follicular development, oocyte maturation,
      steroidogenesis, and ovulation. Dysregulation or naturally occurring mutations of
      the kisspeptin/KISS1R system may negatively affect the ovarian function, leading
      to reproductive pathology or female infertility. A comprehensive understanding of
      the expression, actions, and underlying molecular mechanisms of this system in
      the human ovary is essential for novel approaches to therapeutic and diagnostic
      interventions in reproductive diseases and infertility.

PMID- 29354095
TI  - Watch Out for the "Living Dead": Cell-Free Enzymes and Their Fate.
AB  - Microbes are the engines driving biogeochemical cycles. Microbial extracellular
      enzymatic activities (EEAs) are the "gatekeepers" of the carbon cycle. The total
      EEA is the sum of cell-bound (i.e., cell-attached), and dissolved (i.e., cell
      free) enzyme activities. Cell-free enzymes make up a substantial proportion (up
      to 100%) of the total marine EEA. Although we are learning more about how
      microbial diversity and function (including total EEA) will be affected by
      environmental changes, little is known about what factors control the importance
      of the abundant cell-free enzymes. Since cell-attached EEAs are linked to the
      cell, their fate will likely be linked to the factors controlling the cell's
      fate. In contrast, cell-free enzymes belong to a kind of "living dead" realm
      because they are not attached to a living cell but still are able to perform
      their function away from the cell; and as such, the factors controlling their
      activity and fate might differ from those affecting cell-attached enzymes. This
      article aims to place cell-free EEA into the wider context of hydrolysis of
      organic matter, deal with recent studies assessing what controls the production,
      activity and lifetime of cell-free EEA, and what their fate might be in response
      to environmental stressors. This perspective article advocates the need to go
      "beyond the living things," studying the response of cells/organisms to different
      stressors, but also to study cell-free enzymes, in order to fully constrain the
      future and evolution of marine biogeochemical cycles.

PMID- 29354094
TI  - Leptin Regulation of Gonadotrope Gonadotropin-Releasing Hormone Receptors As a
      Metabolic Checkpoint and Gateway to Reproductive Competence.
AB  - The adipokine leptin signals the body's nutritional status to the brain, and
      particularly, the hypothalamus. However, leptin receptors (LEPRs) can be found
      all throughout the body and brain, including the pituitary. It is known that
      leptin is permissive for reproduction, and mice that cannot produce leptin
      (Lep/Lep) are infertile. Many studies have pinpointed leptin's regulation of
      reproduction to the hypothalamus. However, LEPRs exist at all levels of the
      hypothalamic-pituitary-gonadal axis. We have previously shown that deleting the
      signaling portion of the LEPR specifically in gonadotropes impairs fertility in
      female mice. Our recent studies have targeted this regulation to the control of
      gonadotropin releasing hormone receptor (GnRHR) expression. The hypotheses
      presented here are twofold: (1) cyclic regulation of pituitary GnRHR levels sets
      up a target metabolic checkpoint for control of the reproductive axis and (2)
      multiple checkpoints are required for the metabolic signaling that regulates the
      reproductive axis. Here, we emphasize and explore the relationship between the
      hypothalamus and the pituitary with regard to the regulation of GnRHR. The
      original data we present strengthen these hypotheses and build on our previous
      studies. We show that we can cause infertility in 70% of female mice by deleting
      all isoforms of LEPR specifically in gonadotropes. Our findings implicate activin
      subunit (InhBa) mRNA as a potential leptin target in gonadotropes. We further
      show gonadotrope-specific upregulation of GnRHR protein (but not mRNA levels)
      following leptin stimulation. In order to try and understand this post
      transcriptional regulation, we tested candidate miRNAs (identified with in silico
      analysis) that may be binding the Gnrhr mRNA. We show significant upregulation of
      one of these miRNAs in our gonadotrope-Lepr-null females. The evidence provided
      here, combined with our previous work, lay the foundation for metabolically
      regulated post-transcriptional control of the gonadotrope. We discuss possible
      mechanisms, including miRNA regulation and the involvement of the RNA binding
      protein, Musashi. We also demonstrate how this regulation may be vital for the
      dynamic remodeling of gonadotropes in the cycling female. Finally, we propose
      that the leptin receptivity of both the hypothalamus and the pituitary are vital
      for the body's ability to delay or slow reproduction during periods of low
      nutrition.

PMID- 29354097
TI  - Marine Fungi: A Source of Potential Anticancer Compounds.
AB  - Metabolites from marine fungi have hogged the limelight in drug discovery because
      of their promise as therapeutic agents. A number of metabolites related to marine
      fungi have been discovered from various sources which are known to possess a
      range of activities as antibacterial, antiviral and anticancer agents. Although,
      over a thousand marine fungi based metabolites have already been reported, none
      of them have reached the market yet which could partly be related to non
      comprehensive screening approaches and lack of sustained lead optimization. The
      origin of these marine fungal metabolites is varied as their habitats have been
      reported from various sources such as sponge, algae, mangrove derived fungi, and
      fungi from bottom sediments. The importance of these natural compounds is based
      on their cytotoxicity and related activities that emanate from the diversity in
      their chemical structures and functional groups present on them. This review
      covers the majority of anticancer compounds isolated from marine fungi during
      2012-2016 against specific cancer cell lines.

PMID- 29354096
TI  - Beta and Gamma Human Herpesviruses: Agonistic and Antagonistic Interactions with
      the Host Immune System.
AB  - Viruses are the most abundant and diverse biological entities in the planet.
      Historically, our main interest in viruses has focused on their pathogenic role,
      recognized by pandemics that have decimated the world population. However, viral
      infections have also played a major role in the evolution of cellular organisms,
      both through interchanging of genes with novel functions and shaping the immune
      system. Examples abound of infections that seriously compromise the host
      integrity, but evidence of plant and insect viruses mutualistic relationships
      have recently surfaced in which infected hosts are better suited for survival,
      arguing that virus-host interactions are initially parasitic but become
      mutualistic over years of co-evolution. A similar mutual help scenario has
      emerged with commensal gut bacteria. EBV is a herpesvirus that shares more than a
      hundred million years of co-evolution with humans, today successfully infecting
      close to 100% of the adult world population. Infection is usually acquired early
      in childhood persisting for the host lifetime mostly without apparent clinical
      symptoms. Disturbance of this homeostasis is rare and results in several
      diseases, of which the best understood are infectious mononucleosis and several
      EBV-associated cancers. Less understood are recently found inborn errors of the
      immune system that result in primary immunodeficiencies with an increased
      predisposition almost exclusive to EBV-associated diseases. Puzzling to these
      scenarios of broken homeostasis is the co-existence of immunosuppression,
      inflammation, autoimmunity and cancer. Homologous to EBV, HCMV, HHV-6 and HHV-7
      are herpesviruses that also latently infect most individuals. Several lines of
      evidence support a mutualistic equilibrium between HCMV/EBV and hosts, that when
      altered trigger diseases in which the immune system plays a critical role.
      Interestingly, these beta and gamma herpesviruses persistently infect all immune
      lineages and early precursor cells. In this review, we will discuss the evidence
      of the benefits that infection of immune cells with these herpesviruses brings to
      the host. Also, the circumstances in which this positive relationship is broken,
      predisposing the host to diseases characterized by an abnormal function of the
      host immune system.

PMID- 29354098
TI  - Metavirome Sequencing of the Termite Gut Reveals the Presence of an Unexplored
      Bacteriophage Community.
AB  - The Formosan subterranean termite; Coptotermes formosanus is nutritionally
      dependent on the complex and diverse community of bacteria and protozoa in their
      gut. Although, there have been many studies to decipher the taxonomic and
      functional diversity of bacterial communities in the guts of termites, their
      bacteriophages remain unstudied. We sequenced the metavirome of the guts of
      Formosan subterranean termite workers to study the diversity of bacteriophages
      and other associated viruses. Results showed that the termites harbor a virome in
      their gut comprised of varied and previously unknown bacteriophages. Between 87
      90% of the predicted dsDNA virus genes by Metavir showed similarity to the tailed
      bacteriophages (Caudovirales). Many predicted genes from the virome matched to
      bacterial prophage regions. These data are suggestive of a virome dominated by
      temperate bacteriophages. We predicted the genomes of seven novel Caudovirales
      bacteriophages from the termite gut. Three of these predicted bacteriophage
      genomes were found in high proportions in all the three termite colonies tested.
      Two bacteriophages are predicted to infect endosymbiotic bacteria of the gut
      protozoa. The presence of these putative bacteriophages infecting endosymbionts
      of the gut protozoa, suggests a quadripartite relationship between the termites
      their symbiotic protozoa, endosymbiotic bacteria of the protozoa and their
      bacteriophages. Other than Caudovirales, ss-DNA virus related genes were also
      present in the termite gut. We predicted the genomes of 12 novel Microviridae
      phages from the termite gut and seven of those possibly represent a new proposed
      subfamily. Circovirus like genomes were also assembled from the termite gut at
      lower relative abundance. We predicted 10 novel circovirus genomes in this study.
      Whether these circoviruses infect the termites remains elusive at the moment. The
      functional and taxonomical annotations suggest that the termites may harbor a
      core virome comprised of the bacteriophages infecting endosymbionts of the gut
      protozoa.

PMID- 29354099
TI  - Rhizobium sp. IRBG74 Alters Arabidopsis Root Development by Affecting Auxin
      Signaling.
AB  - Rhizobium sp. IRBG74 not only nodulates Sesbania cannabina but also can enhance
      rice growth; however, the underlying molecular mechanisms are not clear. Here, we
      show that Rhizobium sp. IRBG74 colonizes the roots of Arabidopsis thaliana, which
      leads to inhibition in the growth of main root but enhancement in the formation
      of lateral roots. The promotion of lateral root formation by Rhizobium sp. IRBG74
      in the fls2-1 mutant, which is insensitive to flagellin, is similar to the wild
      type plant, while the auxin response deficient mutant tir1-1 is significantly
      less sensitive to Rhizobium sp. IRBG74 than the wild type in terms of the
      inhibition of main root elongation and the promotion of lateral root formation.
      Further transcriptome analysis of Arabidopsis roots inoculated with Rhizobium sp.
      IRBG74 revealed differential expression of 50 and 211 genes at 24 and 48 h,
      respectively, and a majority of these genes are involved in auxin signaling.
      Consistent with the transcriptome analysis results, Rhizobium sp. IRBG74
      treatment induces expression of the auxin responsive reporter DR5:GUS in roots.
      Our results suggest that in Arabidopsis Rhizobium sp. IRBG74 colonizes roots and
      promotes the lateral root formation likely through modulating auxin signaling.
      Our work provides insight into the molecular mechanisms of interactions between
      legume-nodulating rhizobia and non-legume plants.

PMID- 29354100
TI  - SesI May Be Associated with the Invasiveness of Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is a commensal bacterium which widely colonizes in
      human skin and mucous membrane and rarely causes clinically manifested
      infections. S. epidermidis surface protein I (SesI) is considered to be the major
      virulence factor of S. epidermidis infection, but its pathogenesis is not clear.
      Here, we demonstrated that the prevalence of sesI among S. epidermidis invasive
      isolates (20.8%, 26/125) was significantly higher than that among colonizing
      isolates (3.8%, 4/106). The positive rates of biofilm-associated genes (aap,
      icaA, IS256) and resistance-associated genes mupA among the sesI-positive
      isolates were significantly higher than those among sesI-negative isolates (p <
      0.05). And antimicrobial susceptibility testing showed that the resistance rates
      of sesI-positive isolates to ciprofloxacin, gentamicin and
      trimethoprim/sulfamethoxazole were significantly higher than those among sesI
      negative isolates. Interestingly, 80.8% (21/26) of sesI-positive isolates belong
      to ST2 determined by MLST, while ST2 was not found among any of the 99 sesI
      negative invasive isolates, indicating that there is a strong association between
      carriage of sesI and ST2 clone. In order to further study the role of sesI gene
      in pathogenesis, the sesI gene mutant (S. epidermidis RP62ADeltasesI) and
      complementary expression strain (S. epidermidis RP62ADeltasesI-C) were
      successfully constructed. All experimental data indicated that sesI may promote
      S. epidermidis to adhere and aggregate, but it had no obvious effect on the
      mature stage of biofilm formation. Taken together, these results suggest that
      sesI, along with antimicrobial and other biofilm-associated genes enables S.
      epidermidis easier for colonization and adhesion and contributes to the spread of
      S. epidermidis, especially ST2 clone.

PMID- 29354101
TI  - Know Your Enemy: Successful Bioinformatic Approaches to Predict Functional RNA
      Structures in Viral RNAs.
AB  - Structured RNA elements may control virus replication, transcription and
      translation, and their distinct features are being exploited by novel antiviral
      strategies. Viral RNA elements continue to be discovered using combinations of
      experimental and computational analyses. However, the wealth of sequence data,
      notably from deep viral RNA sequencing, viromes, and metagenomes, necessitates
      computational approaches being used as an essential discovery tool. In this
      review, we describe practical approaches being used to discover functional RNA
      elements in viral genomes. In addition to success stories in new and emerging
      viruses, these approaches have revealed some surprising new features of well
      studied viruses e.g., human immunodeficiency virus, hepatitis C virus, influenza,
      and dengue viruses. Some notable discoveries were facilitated by new comparative
      analyses of diverse viral genome alignments. Importantly, comparative approaches
      for finding RNA elements embedded in coding and non-coding regions differ. With
      the exponential growth of computer power we have progressed from stem-loop
      prediction on single sequences to cutting edge 3D prediction, and from command
      line to user friendly web interfaces. Despite these advances, many powerful, user
      friendly prediction tools and resources are underutilized by the virology
      community.

PMID- 29354104
TI  - Serum Metabolic Profiling of Oocyst-Induced Toxoplasma gondii Acute and Chronic
      Infections in Mice Using Mass-Spectrometry.
AB  - Toxoplasma gondii is an obligate intracellular parasite causing severe diseases
      in immunocompromised individuals and congenitally infected neonates, such as
      encephalitis and chorioretinitis. This study aimed to determine whether serum
      metabolic profiling can (i) identify metabolites associated with oocyst-induced
      T. gondii infection and (ii) detect systemic metabolic differences between T.
      gondii-infected mice and controls. We performed the first global metabolomics
      analysis of mice serum challenged with 100 sporulated T. gondii Pru oocysts
      (Genotype II). Sera from acutely infected mice (11 days post-infection, dpi),
      chronically infected mice (33 dpi) and control mice were collected and analyzed
      using LC-MS/MS platform. Following False Discovery Rate filtering, we identified
      3871 and 2825 ions in ESI+ or ESI- mode, respectively. Principal Component
      Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA)
      identified metabolomic profiles that clearly differentiated T. gondii-infected
      and -uninfected serum samples. Acute infection significantly influenced the serum
      metabolome. Our results identified common and uniquely perturbed metabolites and
      pathways. Acutely infected mice showed perturbations in metabolites associated
      with glycerophospholipid metabolism, biosynthesis of amino acid, and tyrosine
      metabolism. These findings demonstrated that acute T. gondii infection induces a
      global perturbation of mice serum metabolome, providing new insights into the
      mechanisms underlying systemic metabolic changes during early stage of T. gondii
      infection.

PMID- 29354102
TI  - Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in
      Jurkat T Cells.
AB  - Hepatitis C virus core protein is a highly basic viral protein that multimerizes
      with itself to form the viral capsid. When expressed in CD4+ T lymphocytes, it
      can induce modifications in several essential cellular and biological networks.
      To shed light on the mechanisms underlying the alterations caused by the viral
      protein, we have analyzed HCV-core subcellular localization and its associations
      with host proteins in Jurkat T cells. In order to investigate the intracellular
      localization of Hepatitis C virus core protein, we have used a lentiviral system
      to transduce Jurkat T cells and subsequently localize the protein using
      immunoelectron microscopy techniques. We found that in Jurkat T cells, Hepatitis
      C virus core protein mostly localizes in the nucleus and specifically in the
      nucleolus. In addition, we performed pull-down assays combined with Mass
      Spectrometry Analysis, to identify proteins that associate with Hepatitis C virus
      core in Jurkat T cells. We found proteins such as NOLC1, PP1gamma, ILF3, and
      C1QBP implicated in localization and/or traffic to the nucleolus. HCV-core
      associated proteins are implicated in RNA processing and RNA virus infection as
      well as in functions previously shown to be altered in Hepatitis C virus core
      expressing CD4+ T cells, such as cell cycle delay, decreased proliferation, and
      induction of a regulatory phenotype. Thus, in the current work, we show the
      ultrastructural localization of Hepatitis C virus core and the first profile of
      HCV core associated proteins in T cells, and we discuss the functions and
      interconnections of these proteins in molecular networks where relevant
      biological modifications have been described upon the expression of Hepatitis C
      virus core protein. Thereby, the current work constitutes a necessary step toward
      understanding the mechanisms underlying HCV core mediated alterations that had
      been described in relevant biological processes in CD4+ T cells.

PMID- 29354103
TI  - Time Course-Dependent Methanogenic Crude Oil Biodegradation: Dynamics of Fumarate
      Addition Metabolites, Biodegradative Genes, and Microbial Community Composition.
AB  - Biodegradation of crude oil in subsurface petroleum reservoirs has adversely
      impacted most of the world's oil, converting this resource to heavier forms that
      are of lower quality and more challenging to recover. Oil degradation in deep
      reservoir environments has been attributed to methanogenesis over geological
      time, yet our understanding of the processes and organisms mediating oil
      transformation in the absence of electron acceptors remains incomplete. Here, we
      sought to identify hydrocarbon activation mechanisms and reservoir-associated
      microorganisms that may have helped shape the formation of biodegraded oil by
      incubating oilfield produced water in the presence of light ( degrees API = 32)
      or heavy crude oil ( degrees API = 16). Over the course of 17 months, we
      conducted routine analytical (GC, GC-MS) and molecular (PCR/qPCR of assA and bssA
      genes, 16S rRNA gene sequencing) surveys to assess microbial community
      composition and activity changes over time. Over the incubation period, we
      detected the formation of transient hydrocarbon metabolites indicative of alkane
      and alkylbenzene addition to fumarate, corresponding with increases in methane
      production and fumarate addition gene abundance. Chemical and gene-based evidence
      of hydrocarbon biodegradation under methanogenic conditions was supported by the
      enrichment of hydrocarbon fermenters known to catalyze fumarate addition
      reactions (e.g., Desulfotomaculum, Smithella), along with syntrophic bacteria
      (Syntrophus), methanogenic archaea, and several candidate phyla (e.g.,
      "Atribacteria", "Cloacimonetes"). Our results reveal that fumarate addition is a
      possible mechanism for catalyzing the methanogenic biodegradation of susceptible
      saturates and aromatic hydrocarbons in crude oil, and we propose the roles of
      community members and candidate phyla in our cultures that may be involved in
      hydrocarbon transformation to methane in crude oil systems.

PMID- 29354105
TI  - Labilibaculum manganireducens gen. nov., sp. nov. and Labilibaculum filiforme sp.
      nov., Novel Bacteroidetes Isolated from Subsurface Sediments of the Baltic Sea.
AB  - Microbial communities in deep subsurface sediments are challenged by the decrease
      in amount and quality of organic substrates with depth. In sediments of the
      Baltic Sea, they might additionally have to cope with an increase in salinity
      from ions that have diffused downward from the overlying water during the last
      9000 years. Here, we report the isolation and characterization of four novel
      bacteria of the Bacteroidetes from depths of 14-52 m below seafloor (mbsf) of
      Baltic Sea sediments sampled during International Ocean Discovery Program (IODP)
      Expedition 347. Based on physiological, chemotaxonomic and genotypic
      characterization, we propose that the four strains represent two new species
      within a new genus in the family Marinifilaceae, with the proposed names
      Labilibaculum manganireducens gen. nov., sp. nov. (type strain 59.10-2MT) and
      Labilibaculum filiforme sp. nov. (type strains 59.16BT) with additional strains
      of this species (59.10-1M and 60.6M). The draft genomes of the two type strains
      had sizes of 5.2 and 5.3 Mb and reflected the major physiological capabilities.
      The strains showed gliding motility, were psychrotolerant, neutrophilic and
      halotolerant. Growth by fermentation of mono- and disaccharides as well as
      pyruvate, lactate and glycerol was observed. During glucose fermentation, small
      amounts of electron equivalents were transferred to Fe(III) by all strains, while
      one of the strains also reduced Mn(IV). Thereby, the four strains broaden the
      phylogenetic range of prokaryotes known to reduce metals to the group of
      Bacteroidetes. Halotolerance and metal reduction might both be beneficial for
      survival in deep subsurface sediments of the Baltic Sea.

PMID- 29354106
TI  - Temporal and Spatial Impact of Human Cadaver Decomposition on Soil Bacterial and
      Arthropod Community Structure and Function.
AB  - As vertebrate carrion decomposes, there is a release of nutrient-rich fluids into
      the underlying soil, which can impact associated biological community structure
      and function. How these changes alter soil biogeochemical cycles is relatively
      unknown and may prove useful in the identification of carrion decomposition
      islands that have long lasting, focal ecological effects. This study investigated
      the spatial (0, 1, and 5 m) and temporal (3-732 days) dynamics of human cadaver
      decomposition on soil bacterial and arthropod community structure and microbial
      function. We observed strong evidence of a predictable response to cadaver
      decomposition that varies over space for soil bacterial and arthropod community
      structure, carbon (C) mineralization and microbial substrate utilization
      patterns. In the presence of a cadaver (i.e., 0 m samples), the relative
      abundance of Bacteroidetes and Firmicutes was greater, while the relative
      abundance of Acidobacteria, Chloroflexi, Gemmatimonadetes, and Verrucomicrobia
      was lower when compared to samples at 1 and 5 m. Micro-arthropods were more
      abundant (15 to 17-fold) in soils collected at 0 m compared to either 1 or 5 m,
      but overall, micro-arthropod community composition was unrelated to either
      bacterial community composition or function. Bacterial community structure and
      microbial function also exhibited temporal relationships, whereas arthropod
      community structure did not. Cumulative precipitation was more effective in
      predicting temporal variations in bacterial abundance and microbial activity than
      accumulated degree days. In the presence of the cadaver (i.e., 0 m samples), the
      relative abundance of Actinobacteria increased significantly with cumulative
      precipitation. Furthermore, soil bacterial communities and C mineralization were
      sensitive to the introduction of human cadavers as they diverged from baseline
      levels and did not recover completely in approximately 2 years. These data are
      valuable for understanding ecosystem function surrounding carrion decomposition
      islands and can be applicable to environmental bio-monitoring and forensic
      sciences.

PMID- 29354108
TI  - Functional Characteristics of the Flying Squirrel's Cecal Microbiota under a Leaf
      Based Diet, Based on Multiple Meta-Omic Profiling.
AB  - Mammalian herbivores rely on microbial activities in an expanded gut chamber to
      convert plant biomass into absorbable nutrients. Distinct from ruminants, small
      herbivores typically have a simple stomach but an enlarged cecum to harbor
      symbiotic microbes; however, knowledge of this specialized gut structure and
      characteristics of its microbial contents is limited. Here, we used leaf-eating
      flying squirrels as a model to explore functional characteristics of the cecal
      microbiota adapted to a high-fiber, toxin-rich diet. Specifically, environmental
      conditions across gut regions were evaluated by measuring mass, pH, feed particle
      size, and metabolomes. Then, parallel metagenomes and metatranscriptomes were
      used to detect microbial functions corresponding to the cecal environment. Based
      on metabolomic profiles, >600 phytochemical compounds were detected, although
      many were present only in the foregut and probably degraded or transformed by gut
      microbes in the hindgut. Based on metagenomic (DNA) and metatranscriptomic (RNA)
      profiles, taxonomic compositions of the cecal microbiota were dominated by
      bacteria of the Firmicutes taxa; they contained major gene functions related to
      degradation and fermentation of leaf-derived compounds. Based on functional
      compositions, genes related to multidrug exporters were rich in microbial
      genomes, whereas genes involved in nutrient importers were rich in microbial
      transcriptomes. In addition, genes encoding chemotaxis-associated components and
      glycoside hydrolases specific for plant beta-glycosidic linkages were abundant in
      both DNA and RNA. This exploratory study provides findings which may help to form
      molecular-based hypotheses regarding functional contributions of symbiotic gut
      microbiota in small herbivores with folivorous dietary habits.

PMID- 29354107
TI  - Metabolic Adaptation of a C-Terminal Protease A-Deficient Rhizobium leguminosarum
      in Response to Loss of Nutrient Transport.
AB  - Post-translational modification expands the functionality of the proteome beyond
      genetic encoding, impacting many cellular processes. Cleavage of the carboxyl
      terminus is one of the many different ways proteins can be modified for
      functionality. Gel-electrophoresis and mass spectrometric-based techniques were
      used to identify proteins impacted by deficiency of a C-terminal protease, CtpA,
      in Rhizobium leguminosarum bv. viciae 3841. Predicted CtpA substrates from 2D
      silver stained gels were predominantly outer membrane and transport proteins.
      Proteins with altered abundance in the wild type and ctpA (RL4692) mutant,
      separated by 2D difference gel electrophoresis, were selected for analysis by
      mass spectrometry. Of those identified, 9 were the periplasmic solute-binding
      components of ABC transporters, 5 were amino acid metabolic enzymes, 2 were
      proteins involved in sulfur metabolism, and 1 each was related to carbon
      metabolism, protein folding and signal transduction. Alterations to ABC-binding
      cassette transporters, nutrient uptake efficiency and to amino acid metabolism
      indicated an impact on amino acid metabolism and transport for the ctpA mutant,
      which was validated by measured amino acid levels.

PMID- 29354111
TI  - Editorial: Engineering Rumen Metabolic Pathways: Where We Are, and Where Are We
      Heading.

PMID- 29354110
TI  - Stochastic Individual-Based Modeling of Bacterial Growth and Division Using Flow
      Cytometry.
AB  - A realistic description of the variability in bacterial growth and division is
      critical to produce reliable predictions of safety risks along the food chain.
      Individual-based modeling of bacteria provides the theoretical framework to deal
      with this variability, but it requires information about the individual behavior
      of bacteria inside populations. In this work, we overcome this problem by
      estimating the individual behavior of bacteria from population statistics
      obtained with flow cytometry. For this objective, a stochastic individual-based
      modeling framework is defined based on standard assumptions during division and
      exponential growth. The unknown single-cell parameters required for running the
      individual-based modeling simulations, such as cell size growth rate, are
      estimated from the flow cytometry data. Instead of using directly the individual
      based model, we make use of a modified Fokker-Plank equation. This only equation
      simulates the population statistics in function of the unknown single-cell
      parameters. We test the validity of the approach by modeling the growth and
      division of Pediococcus acidilactici within the exponential phase. Estimations
      reveal the statistics of cell growth and division using only data from flow
      cytometry at a given time. From the relationship between the mother and daughter
      volumes, we also predict that P. acidilactici divide into two successive parallel
      planes.

PMID- 29354109
TI  - Characterization of the Skin Microbiota of the Cane Toad Rhinella cf. marina in
      Puerto Rico and Costa Rica.
AB  - Rhinella marina is a toad native to South America that has been introduced in the
      Antilles, likely carrying high loads of microorganisms, potentially impacting
      local community diversity. The amphibian skin is involved in pathogen defense and
      its microbiota has been relatively well studied, however, research focusing on
      the cane toad microbiota is lacking. We hypothesize that the skin microbial
      communities will differ between toads inhabiting different geographical regions
      in Central America and the Caribbean. To test our hypothesis, we compared the
      microbiota of three populations of R. cf. marina toads, two from Costa Rican
      (native) and one Puerto Rican (exotic) locations. In Costa Rica, we collected 11
      toads, 7 in Sarapiqui and 4 from Turrialba while in Puerto Rico, 10 animals were
      collected in Santa Ana. Separate swab samples were collected from the dorsal and
      ventral sites resulting in 42 samples. We found significant differences in the
      structure of the microbial communities between Puerto Rico and Costa Rica. We
      detected as much as 35 different phyla; however, communities were dominated by
      Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Alpha diversity
      and richness were significantly higher in toads from Puerto Rico and
      betadiversity revealed significant differences between the microbiota samples
      from the two countries. At the genus level, we found in Santa Ana, Puerto Rico, a
      high dominance of Kokuria, Niabella, and Rhodobacteraceae, while in Costa Rica we
      found Halomonas and Pseudomonas in Sarapiqui, and Acinetobacter and Citrobacter
      in Turrialba. This is the first report of Niabella associated with the amphibian
      skin. The core microbiome represented 128 Operational Taxonomic Units (OTUs)
      mainly from five genera shared among all samples, which may represent the
      symbiotic Rhinella's skin. These results provide insights into the habitat
      induced microbial changes facing this amphibian species. The differences in the
      microbial diversity in Puerto Rican toads compared to those in Costa Rica provide
      additional evidence of the geographically induced patterns in the amphibian skin
      microbiome, and highlight the importance of discussing the microbial tradeoffs in
      the colonization of new ecosystems.

PMID- 29354112
TI  - Digital Image Analysis of Yeast Single Cells Growing in Two Different Oxygen
      Concentrations to Analyze the Population Growth and to Assist Individual-Based
      Modeling.
AB  - Nowadays control of the growth of Saccharomyces to obtain biomass or cellular
      wall components is crucial for specific industrial applications. The general aim
      of this contribution is to deal with experimental data obtained from yeast cells
      and from yeast cultures to attempt the integration of the two levels of
      information, individual and population, to progress in the control of yeast
      biotechnological processes by means of the overall analysis of this set of
      experimental data, and to assist in the improvement of an individual-based model,
      namely, INDISIM-Saccha. Populations of S. cerevisiae growing in liquid batch
      culture, in aerobic and microaerophilic conditions, were studied. A set of
      digital images was taken during the population growth, and a protocol for the
      treatment and analyses of the images obtained was established. The piecewise
      linear model of Buchanan was adjusted to the temporal evolutions of the yeast
      populations to determine the kinetic parameters and changes of growth phases. In
      parallel, for all the yeast cells analyzed, values of direct morphological
      parameters, such as area, perimeter, major diameter, minor diameter, and derived
      ones, such as circularity and elongation, were obtained. Graphical and numerical
      methods from descriptive statistics were applied to these data to characterize
      the growth phases and the budding state of the yeast cells in both experimental
      conditions, and inferential statistical methods were used to compare the diverse
      groups of data achieved. Oxidative metabolism of yeast in a medium with oxygen
      available and low initial sugar concentration can be taken into account in order
      to obtain a greater number of cells or larger cells. Morphological parameters
      were analyzed statistically to identify which were the most useful for the
      discrimination of the different states, according to budding and/or growth phase,
      in aerobic and microaerophilic conditions. The use of the experimental data for
      subsequent modeling work was then discussed and compared to simulation results
      generated with INDISIM-Saccha, which allowed us to advance in the development of
      this yeast model, and illustrated the utility of data at different levels of
      observation and the needs and logic behind the development of a microbial
      individual-based model.

PMID- 29354113
TI  - Insights into Structural and Mechanistic Features of Viral IRES Elements.
AB  - Internal ribosome entry site (IRES) elements are cis-acting RNA regions that
      promote internal initiation of protein synthesis using cap-independent
      mechanisms. However, distinct types of IRES elements present in the genome of
      various RNA viruses perform the same function despite lacking conservation of
      sequence and secondary RNA structure. Likewise, IRES elements differ in host
      factor requirement to recruit the ribosomal subunits. In spite of this diversity,
      evolutionarily conserved motifs in each family of RNA viruses preserve sequences
      impacting on RNA structure and RNA-protein interactions important for IRES
      activity. Indeed, IRES elements adopting remarkable different structural
      organizations contain RNA structural motifs that play an essential role in
      recruiting ribosomes, initiation factors and/or RNA-binding proteins using
      different mechanisms. Therefore, given that a universal IRES motif remains
      elusive, it is critical to understand how diverse structural motifs deliver
      functions relevant for IRES activity. This will be useful for understanding the
      molecular mechanisms beyond cap-independent translation, as well as the
      evolutionary history of these regulatory elements. Moreover, it could improve the
      accuracy to predict IRES-like motifs hidden in genome sequences. This review
      summarizes recent advances on the diversity and biological relevance of RNA
      structural motifs for viral IRES elements.

PMID- 29354114
TI  - The Expressed MicroRNA-mRNA Interactions of Toxoplasma gondii.
AB  - MicroRNAs (miRNAs) are involved in post-transcriptional modulation of gene
      expression and thereby have a large influence on the resulting phenotype. We have
      previously shown that miRNAs may be involved in the communication between
      Toxoplasma gondii and its hosts and further confirmed a number of proposed
      specific miRNAs. Yet, little is known about the internal regulation via miRNAs in
      T. gondii. Therefore, we predicted pre-miRNAs directly from the type II ME49
      genome and filtered them. For the confident hairpins, we predicted the location
      of the mature miRNAs and established their target genes. To add further
      confidence, we evaluated whether the hairpins and their targets were co
      expressed. Such co-expressed miRNA and target pairs define a functional
      interaction. We extracted all such functional interactions and analyzed their
      differential expression among strains of all three clonal lineages (RH, PLK, and
      CTG) and between the two stages present in the intermediate host (tachyzoites and
      bradyzoites). Overall, we found ~65,000 expressed interactions of which ~5,500
      are differentially expressed among strains but none are significantly
      differentially expressed between developmental stages. Since miRNAs and target
      decoys can be used as therapeutics we believe that the list of interactions we
      provide will lead to novel approaches in the treatment of toxoplasmosis.

PMID- 29354116
TI  - Natural Killer Cell-Based Immunotherapy in Gynecologic Malignancy: A Review.
AB  - Harnessing the immune system has proven an effective therapy in treating
      malignancies. Since the discovery of natural killer (NK) cells, strategies aimed
      to manipulate and augment their effector function against cancer have been the
      subject of intense research. Recent progress in the immunobiology of NK cells has
      led to the development of promising therapeutic approaches. In this review, we
      will focus on the recent advances in NK cell immunobiology and the clinical
      application of NK cell immunotherapy in ovarian, cervical, and uterine cancer.

PMID- 29354119
TI  - Peripheral White Blood Cell Subsets in Metastatic Colorectal Cancer Patients
      Treated with Cetuximab: The Potential Clinical Relevance.
AB  - It was demonstrated that cetuximab-induced tumor regression is based on the
      effects exerted by immune cells included mainly in the innate immune response.
      Therefore, the focus of this study was to explore the alterations in the
      percentages of CD16+, and/or CD56+ lymphocytes, which are comprised of NK cells,
      and minority of CD56+CD3+ cells, in patients with metastatic colorectal cancer
      before or 2 months after the treatment with cetuximab-based regimens associated
      with the response to therapy. The changes in the percentages of lymphocytes and
      granulocytes in these patients were evaluated as well. We enrolled 50 patients
      with wild-type KRAS metastatic colorectal cancer. Disease progression was
      observed in 11/50 patients (non-responders), while other patients achieved
      partial response or stable disease (responders). Control groups included up to 72
      healthy individuals. A significant decrease in the percentages of CD56+ and
      CD16+CD56+ lymphocytes together with a significant decrease in the percentage of
      lymphocytes and an increase in the ratio of granulocyte to lymphocyte percentages
      were observed in patients with metastatic colorectal cancer before therapy,
      compared with those in the healthy individuals. In contrast to those in the
      responders, the percentage of CD16+ lymphocytes in the overall white blood cell
      pool was shown to be significantly decreased in the non-responders, together with
      a significantly decreased percentage of lymphocytes, a significantly increased
      percentage of granulocytes, and an increased ratio of granulocyte to lymphocyte
      percentages before treatment compared with those in the healthy controls. Two
      months after the initiation of the treatment, significantly decreased percentages
      of CD16+, CD56+, and CD16+CD56+ lymphocytes were observed in patients, compared
      with those determined in the healthy controls. The same changes in the amounts of
      circulating immune cells were also observed in the responder subgroup, but the
      percentages of CD16+, CD56+, and CD16+CD56+ lymphocytes 2 months after treatment
      in the non-responder group did not differ significantly in comparison with
      healthy individuals. Considerable alterations of immune cell percentages observed
      in patients with metastatic colorectal cancer with disease progression indicate
      that the assessment of peripheral white blood cell architecture before treatment
      initiation may be clinically relevant.

PMID- 29354118
TI  - Efficacy of a Virus-Like Nanoparticle As Treatment for a Chronic Viral Infection
      Is Hindered by IRAK1 Regulation and Antibody Interference.
AB  - Although vaccination has been an effective way of preventing infections ever
      since the eighteenth century, the generation of therapeutic vaccines and
      immunotherapies is still a work in progress. A number of challenges impede the
      development of these therapeutic approaches such as safety issues related to the
      administration of whole pathogens whether attenuated or inactivated. One safe
      alternative to classical vaccination methods gaining recognition is the use of
      nanoparticles, whether synthetic or naturally derived. We have recently
      demonstrated that the papaya mosaic virus (PapMV)-like nanoparticle can be used
      as a prophylactic vaccine against various viral and bacterial infections through
      the induction of protective humoral and cellular immune responses. Moreover,
      PapMV is also very efficient when used as an immune adjuvant in an
      immunotherapeutic setting at slowing down the growth of aggressive mouse melanoma
      tumors in a type I interferon (IFN-I)-dependent manner. In the present study, we
      were interested in exploiting the capacity of PapMV of inducing robust IFN-I
      production as treatment for the chronic viral infection model lymphocytic
      choriomeningitis virus (LCMV) clone 13 (Cl13). Treatment of LCMV Cl13-infected
      mice with two systemic administrations of PapMV was ineffective, as shown by the
      lack of changes in viral titers and immune response to LCMV following treatment.
      Moreover, IFN-alpha production following PapMV administration was almost
      completely abolished in LCMV-infected mice. To better isolate the mechanisms at
      play, we determined the influence of a pretreatment with PapMV on secondary PapMV
      administration, therefore eliminating potential variables emanating from the
      infection. Pretreatment with PapMV led to the same outcome as an LCMV infection
      in that IFN-alpha production following secondary PapMV immunization was abrogated
      for up to 50 days while immune activation was also dramatically impaired. We
      showed that two distinct and overlapping mechanisms were responsible for this
      outcome. While short-term inhibition was partially the result of interleukin-1
      receptor-associated kinase 1 degradation, a crucial component of the toll-like
      receptor 7 signaling pathway, long-term inhibition was mainly due to interference
      by PapMV-specific antibodies. Thus, we identified a possible pitfall in the use
      of virus-like particles for the systemic treatment of chronic viral infections
      and discuss mitigating alternatives to circumvent these potential problems.

PMID- 29354117
TI  - Inhibiting the Ins and Outs of HIV Replication: Cell-Intrinsic Antiretroviral
      Restrictions at the Plasma Membrane.
AB  - Like all viruses, human immunodeficiency viruses (HIVs) and their primate
      lentivirus relatives must enter cells in order to replicate and, once produced,
      new virions need to exit to spread to new targets. These processes require the
      virus to cross the plasma membrane of the cell twice: once via fusion mediated by
      the envelope glycoprotein to deliver the viral core into the cytosol; and
      secondly by ESCRT-mediated scission of budding virions during release. This
      physical barrier thus presents a perfect location for host antiviral restrictions
      that target enveloped viruses in general. In this review we will examine the
      current understanding of innate host antiviral defences that inhibit these
      essential replicative steps of primate lentiviruses associated with the plasma
      membrane, the mechanism by which these viruses have adapted to evade such
      defences, and the role that this virus/host battleground plays in the
      transmission and pathogenesis of HIV/AIDS.

PMID- 29354121
TI  - Preclinical Characterization of a Novel Monoclonal Antibody NEO-201 for the
      Treatment of Human Carcinomas.
AB  - NEO-201 is a novel humanized IgG1 monoclonal antibody that was derived from an
      immunogenic preparation of tumor-associated antigens from pooled allogeneic colon
      tumor tissue extracts. It was found to react against a variety of cultured human
      carcinoma cell lines and was highly reactive against the majority of tumor
      tissues from many different carcinomas, including colon, pancreatic, stomach,
      lung, and breast cancers. NEO-201 also exhibited tumor specificity, as the
      majority of normal tissues were not recognized by this antibody. Functional
      assays revealed that treatment with NEO-201 is capable of mediating both antibody
      dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity
      (CDC) against tumor cells. Furthermore, the growth of human pancreatic xenograft
      tumors in vivo was largely attenuated by treatment with NEO-201 both alone and in
      combination with human peripheral blood mononuclear cells as an effector cell
      source for ADCC. In vivo biodistribution studies in human tumor xenograft-bearing
      mice revealed that NEO-201 preferentially accumulates in the tumor but not organ
      tissue. Finally, a single-dose toxicity study in non-human primates demonstrated
      safety and tolerability of NEO-201, as a transient decrease in circulating
      neutrophils was the only related adverse effect observed. These findings indicate
      that NEO-201 warrants clinical testing as both a novel diagnostic and therapeutic
      agent for the treatment of a broad variety of carcinomas.

PMID- 29354120
TI  - Monocytic Myeloid-Derived Suppressor Cells in Chronic Infections.
AB  - Heterogeneous populations of myeloid regulatory cells (MRC), including monocytes,
      macrophages, dendritic cells, and neutrophils, are found in cancer and infectious
      diseases. The inflammatory environment in solid tumors as well as infectious foci
      with persistent pathogens promotes the development and recruitment of MRC. These
      cells help to resolve inflammation and establish host immune homeostasis by
      restricting T lymphocyte function, inducing regulatory T cells and releasing
      immune suppressive cytokines and enzyme products. Monocytic MRC, also termed
      monocytic myeloid-derived suppressor cells (M-MDSC), are bona fide phagocytes,
      capable of pathogen internalization and persistence, while exerting localized
      suppressive activity. Here, we summarize molecular pathways controlling M-MDSC
      genesis and functions in microbial-induced non-resolved inflammation and
      immunopathology. We focus on the roles of M-MDSC in infections, including
      opportunistic extracellular bacteria and fungi as well as persistent
      intracellular pathogens, such as mycobacteria and certain viruses. Better
      understanding of M-MDSC biology in chronic infections and their role in
      antimicrobial immunity, will advance development of novel, more effective and
      broad-range anti-infective therapies.

PMID- 29354122
TI  - Neurofibromin 1 Impairs Natural Killer T-Cell-Dependent Antitumor Immunity
      against a T-Cell Lymphoma.
AB  - Neurofibromin 1 (NF1) is a tumor suppressor gene encoding a Ras GTPase that
      negatively regulates Ras signaling pathways. Mutations in NF1 are linked to
      neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome.
      In terms of antitumor immunity, CD1d-dependent natural killer T (NKT) cells play
      an important role in the innate antitumor immune response. Generally, Type-I NKT
      cells protect (and Type-II NKT cells impair) host antitumor immunity. We have
      previously shown that CD1d-mediated antigen presentation to NKT cells is
      regulated by cell signaling pathways. To study whether a haploinsufficiency in
      NF1 would affect CD1d-dependent activation of NKT cells, we analyzed the NKT-cell
      population as well as the functional expression of CD1d in Nf1+/- mice. Nf1+/-
      mice were found to have similar levels of NKT cells as wildtype (WT) littermates.
      Interestingly, however, reduced CD1d expression was observed in Nf1+/- mice
      compared with their WT littermates. When inoculated with a T-cell lymphoma in
      vivo, Nf1+/- mice survived longer than their WT littermates. Furthermore,
      blocking CD1d in vivo significantly enhanced antitumor activity in WT, but not in
      Nf1+/- mice. In contrast, a deficiency in Type-I NKT cells increased antitumor
      activity in Nf1+/- mice, but not in WT littermates. Therefore, these data suggest
      that normal NF1 expression impairs CD1d-mediated NKT-cell activation and
      antitumor activity against a T-cell lymphoma.

PMID- 29354123
TI  - Congenital Cytomegalovirus Infection: Maternal-Child HLA-C, HLA-E, and HLA-G
      Affect Clinical Outcome.
AB  - Congenital CMV infection (cCMV) is the most common congenital infection causing
      permanent long-term impairments (LTI). cCMV immunopathogenesis is largely unknown
      due to the complex interplay between viral, maternal, placental, and child
      factors. In this study, a large retrospective nationwide cohort of children with
      cCMV and their mothers was used. HLA-C, HLA-E, and HLA-G were assessed in 96
      mother-child pairs in relation to symptoms at birth and LTI at 6 years of age.
      The mothers were additionally typed for killer cell immunoglobulin-like
      receptors. The maternal HLA-G 14 bp deletion/deletion polymorphism was associated
      with a worse outcome, as the immunomodulation effect of higher protein levels may
      induce less CMV control, with a direct impact on placenta and fetus. The absence
      of maternal HLA-C belonging to the C2 group was associated with symptoms at
      birth, as activating signals on decidual NK may override inhibitory signals,
      contributing to a placental pro-inflammatory environment. Here, the increased HLA
      E*0101 and HLA-C mismatches, which were associated with symptoms at birth, may
      enhance maternal allo-reactivity to fetal Ags, and cause suboptimal viral
      clearance. Finally, HLA-C non-inherited maternal antigens (NIMAs) were associated
      with LTI. The tolerance induced in the fetus toward NIMAs may indirectly induce a
      suboptimal CMV antiviral response throughout childhood. In light of our findings,
      the potential role of maternal-child HLA in controlling CMV infection and cCMV
      related disease, and the clinical value as predictor for long-term outcome
      certainly deserve further evaluation.

PMID- 29354115
TI  - Cytokine-Ion Channel Interactions in Pulmonary Inflammation.
AB  - The lungs conceptually represent a sponge that is interposed in series in the
      bodies' systemic circulation to take up oxygen and eliminate carbon dioxide. As
      such, it matches the huge surface areas of the alveolar epithelium to the
      pulmonary blood capillaries. The lung's constant exposure to the exterior
      necessitates a competent immune system, as evidenced by the association of
      clinical immunodeficiencies with pulmonary infections. From the in utero to the
      postnatal and adult situation, there is an inherent vital need to manage alveolar
      fluid reabsorption, be it postnatally, or in case of hydrostatic or permeability
      edema. Whereas a wealth of literature exists on the physiological basis of fluid
      and solute reabsorption by ion channels and water pores, only sparse knowledge is
      available so far on pathological situations, such as in microbial infection,
      acute lung injury or acute respiratory distress syndrome, and in the pulmonary
      reimplantation response in transplanted lungs. The aim of this review is to
      discuss alveolar liquid clearance in a selection of lung injury models, thereby
      especially focusing on cytokines and mediators that modulate ion channels.
      Inflammation is characterized by complex and probably time-dependent co
      signaling, interactions between the involved cell types, as well as by cell
      demise and barrier dysfunction, which may not uniquely determine a clinical
      picture. This review, therefore, aims to give integrative thoughts and wants to
      foster the unraveling of unmet needs in future research.

PMID- 29354126
TI  - The Antioxidant Procyanidin Reduces Reactive Oxygen Species Signaling in
      Macrophages and Ameliorates Experimental Colitis in Mice.
AB  - Management of inflammatory bowel disease (IBD) is a real clinical challenge.
      Despite intense investigation, the mechanisms of IBD remain substantially
      unidentified. Some inflammatory conditions, such as matrix metalloproteinases
      (MMPs) and the nuclear factor-kappaB (NF-kappaB) and NOD-like receptor protein 3
      (NLRP3) inflammasome signaling pathways, are reported to contribute to the
      development and maintenance of IBD. Regulation of their common upstream
      signaling, that is, reactive oxygen species (ROS), may be important to control
      the progression of IBD. In the present study, we found that procyanidin, a
      powerful antioxidation flavonoid, has a significant effect on ROS clearance on
      THP-1 macrophages after lipopolysaccharide (LPS) or LPS-combined adenosine
      triphosphate stimulation, thus downregulating MMP9 expression, suppressing NF
      kappaB signaling, and interrupting the formation of the NLRP3 inflammasome.
      Moreover, our in vivo data showed that procyanidin attenuated Dextran sulfate
      sodium-induced experimental colitis in a dose-dependent fashion by suppressing
      the expression of MMP9, NF-kappaB, and NLRP3 inflammasome signaling in colonic
      tissues in mice. Overall, our results suggested that targeting ROS could be a
      potential therapeutic choice for colonic inflammation.

PMID- 29354127
TI  - The Clinical Features of Patients with Chronic Hepatitis C Virus Infections Are
      Associated with Killer Cell Immunoglobulin-Like Receptor Genes and Their
      Expression on the Surface of Natural Killer Cells.
AB  - Killer cell immunoglobulin-like receptor (KIR) genes are known to play a role in
      the acute phase of hepatitis C virus (HCV) infection. The present study
      investigated their roles in chronic HCV (CHCV) infection by analyzing the
      phenotypes and function of natural killer (NK) and T cells that express KIRs. T
      cells from CHCV patients showed a more differentiated phenotype, and NK cells
      exhibited an activated profile. These observations are consistent with the
      increased expression of the degranulation marker CD107a observed after PMA
      stimulation. We explored the correlations between the expression of KIR genes and
      lectin type-C receptors with clinical factors that predict progression to
      fibrosis and cirrhosis. The expression levels of KIR2DS3 and the functional
      alleles of KIR2DS4-FL were increased in patients with intermediate and high viral
      loads. Homozygous KIR2DS4 was also associated with the presence of cirrhosis. In
      the group of individuals with a shorter infection time who developed cirrhosis,
      we detected decreased expression of KIR3DL1 in CD56dim NK cells in the presence
      of its ligand. Similarly, in the group of patients with late CHCV infections
      complicated with cirrhosis, we detected lower expression of the strong inhibitory
      receptor NKG2A in CD56bright NK cells. We also detected an increase in NKG2C
      expression in CD56dim NK cells in CHCV patients who displayed high
      necroinflammatory activity. Decreased KIR3DL2 expression in CD56dim and
      CD56bright NK cells was associated with a high body mass index, and KIR3DL2
      expression may be one factor associated with the more rapid progression of CHCV
      to fibrosis in patients.

PMID- 29354125
TI  - Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor.
AB  - With striking similarity to their adaptive T helper cell counterparts, innate
      lymphoid cells (ILCs) represent an emerging family of cell types that express
      signature transcription factors, including T-bet+ Eomes+ natural killer cells, T
      bet+ Eomes- group 1 ILCs, GATA3+ group 2 ILCs, RORgammat+ group 3 ILCs, and newly
      identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of
      the host (e.g., the lung, gut, and skin) at the interface of host-environment
      interactions. Active research has been conducted to elucidate molecular
      mechanisms underlying the development and function of ILCs. The aryl hydrocarbon
      receptor (Ahr) is a ligand-dependent transcription factor, best known to mediate
      the effects of xenobiotic environmental toxins and endogenous microbial and
      dietary metabolites. Here, we review recent progresses regarding Ahr function in
      ILCs. We focus on the Ahr-mediated cross talk between ILCs and other immune/non
      immune cells in host tissues especially in the gut. We discuss the molecular
      mechanisms of the action of Ahr expression and activity in regulation of ILCs in
      immunity and inflammation, and the interaction between Ahr and other
      pathways/transcription factors in ILC development and function with their
      implication in disease.

PMID- 29354128
TI  - Prolonged Deleterious Influences of Chemotherapeutic Agent CPT-11 on Resident
      Peritoneal Macrophages and B1 Cells.
AB  - CPT-11 is a first-line chemotherapeutic agent for the treatment of colorectal
      cancer in clinic. Previous studies including ours have demonstrated that CPT-11
      is, however, toxic to the intestinal epithelium and resident peritoneal
      macrophages. By interacting with B1 cells, the resident peritoneal macrophages
      play critical roles in the maintenance of gastrointestinal homeostasis. It
      remains therefore elusive whether these peritoneal innate immune cells could be
      rebuilt spontaneously or artificially after being impaired by CPT-11
      administration. In this study, we found that mouse resident peritoneal
      macrophages, namely the large peritoneal macrophages (LPMs) with a
      CD11b+F4/80hiGATA6+ phenotype, and B1 (CD19+CD23-) cells were depleted by
      intraperitoneal (i.p.) CPT-11 treatment within 1 week, but reappeared from day 14
      after CPT-11 treatment. However, the recovery processes of these innate immune
      cells were slow, as their counts could not be fully recovered even 2 months
      later, when compared with that of vehicle-treated control group. Interestingly,
      in the peritoneal cavity of the mice treated with CPT-11, the cell counts of LPMs
      and B1 cells were significantly increased after adoptive transfer with syngeneic
      peritoneal exudate cells (PECs) from healthy mice. Adoptive transfer with bone
      marrow cells also slightly increased, although not significantly, the cell counts
      of LPMs and B1 cells in CPT-11-treated mice. The survival rate of bacterial
      infected mice was significantly reduced by i.p. CPT-11 treatment in comparison
      with vehicle-treated or untreated control groups. Besides, oral administration of
      CPT-11 also had a delayed toxicity on the resident peritoneal macrophages. Our
      results suggest that CPT-11 has prolonged deleterious effects on peritoneal
      innate immune cells but adoptive transfer with PECs may accelerate their recovery
      processes, highlighting the potential of adoptive cell transfer as an avenue to
      counteract the adverse effects of this chemotherapeutic agent.

PMID- 29354129
TI  - Vitamin D Enhances Alveolar Development in Antenatal Lipopolysaccharide-Treated
      Rats through the Suppression of Interferon-gamma Production.
AB  - Bronchopulmonary dysplasia (BPD) is characterized by the premature arrest of
      alveolar development. Antenatal exposure to inflammation inhibits lung
      morphogenesis, thereby increasing the risk for the development of BPD. Here, we
      investigated whether vitamin D (VitD) enhances alveolar development in antenatal
      lipopolysaccharide (LPS)-treated rats, which is a model for BPD. We used an
      established animal model of BPD, and random assignment to the control group, LPS
      group, or LPS with VitD group. Levels of interferon (IFN)-gamma and interleukin-4
      were detected by real-time polymerase chain reaction (PCR) and enzyme-linked
      immunosorbent assay. IFN-gamma producing CD8+ T cells were assessed by flow
      cytometry, and the methylation status of the VitD-response element (VDRE) was
      analyzed by bisulfite sequencing PCR. 25-hydroxyvitamin D levels were measured by
      liquid chromatography tandem mass spectrometry in maternal serum samples
      collected from 86 pregnant women in a prospective birth cohort enrolled from 2012
      to 2013. Our results showed that VitD effectively alleviated the simplification
      of the lung alveolar structure in BPD rats and suppressed LPS-induced IFN-gamma
      expression in the lung and spleen tissues. Further investigation revealed that
      VitD suppressed IFN-gamma production in CD8+ T cells. Specifically, VitD
      increased the methylation percentage of the VDRE in the IFN-gamma-promoter region
      and suppressed LPS-induced expression of IFN-gamma. Additionally, we observed an
      association between maternal VitD exposure during pregnancy and neonatal IFN
      gamma levels in a prospective birth cohort, with a trend similar to that observed
      in the animal model. Our data suggested that supplementation of VitD could
      suppress IFN-gamma production, resulting in improved alveolar development in an
      LPS-induced BPD rat model.

PMID- 29354124
TI  - Eat Prey, Live: Dictyostelium discoideum As a Model for Cell-Autonomous Defenses.
AB  - The soil-dwelling social amoeba Dictyostelium discoideum feeds on bacteria. Each
      meal is a potential infection because some bacteria have evolved mechanisms to
      resist predation. To survive such a hostile environment, D. discoideum has in
      turn evolved efficient antimicrobial responses that are intertwined with
      phagocytosis and autophagy, its nutrient acquisition pathways. The core machinery
      and antimicrobial functions of these pathways are conserved in the mononuclear
      phagocytes of mammals, which mediate the initial, innate-immune response to
      infection. In this review, we discuss the advantages and relevance of D.
      discoideum as a model phagocyte to study cell-autonomous defenses. We cover the
      antimicrobial functions of phagocytosis and autophagy and describe the processes
      that create a microbicidal phagosome: acidification and delivery of lytic
      enzymes, generation of reactive oxygen species, and the regulation of Zn2+, Cu2+,
      and Fe2+ availability. High concentrations of metals poison microbes while metal
      sequestration inhibits their metabolic activity. We also describe microbial
      interference with these defenses and highlight observations made first in D.
      discoideum. Finally, we discuss galectins, TNF receptor-associated factors,
      tripartite motif-containing proteins, and signal transducers and activators of
      transcription, microbial restriction factors initially characterized in mammalian
      phagocytes that have either homologs or functional analogs in D. discoideum.

PMID- 29354130
TI  - Ets-2 Acts As a Transcriptional Repressor of the Human Immunodeficiency Virus
      Type 1 through Binding to a Repressor-Activator Target Sequence of 5'-LTR.
AB  - HIV-1 is transcriptionally active in activated T helper (Th)-cells and inactive
      in naive or resting memory Th-cells. Ets-2 is a preinduction transcriptional
      repressor of the IL-2 gene in naive Th-cells and a candidate transcriptional
      repressor of HIV-1 in the same cells, because the -279 to -250 upstream region of
      HIV-1-LTR [repressor-activator target sequence (RATS)], that participates in HIV
      1-LTR transcriptional silencing, encompasses the AAGGAG Ets-2 binding site. In
      this proof of concept study, we investigated whether Ets-2 represses the
      expression of HIV-1. To assess whether Ets-2 can repress HIV-1 transcriptional
      activation acting through RATS, we transfected Jurkat cells with an Ets-2
      overexpression plasmid (pCDNA3-ets-2) or Ets-2 silencing plasmids (ets-2-shRNA)
      and, as target genes, plasmids carrying the whole HIV-1-LTR sequence (HIV-1-LTR
      CAT) or two copies of the RATS sequence (2* RATS-CAT) or a point mutation in the
      Ets-2 binding site (2* mutantRATS-CAT) or CMV-CAT (control). Ets-2 overexpression
      resulted in a significant reduction of HIV-1-LTR-CAT and 2* RATS-CAT activities
      in stimulated cells, but not of the 2* mutantRATS-CAT or CMV-CAT. Ets-2 silencing
      led to increased activities of HIV-1-LTR-CAT and 2* RATS-CAT in unstimulated
      cells, but had no effect on the activities of 2* mutantRATS-CAT and CMV-CAT. To
      assess Ets-2 binding to HIV-1-LTR-RATS in naive Th-cells, we isolated naive Th
      cell nuclear proteins and passed them through an Ets-2 antibody column;
      electrophoretic mobility shift assays were performed using an RATS probe mixed
      with consecutive protein eluates. Ets-2 bound to the HIV-1-LTR-RATS in a dose
      dependent manner. To assess Ets-2 binding to RATS in vivo, Jurkat cells were
      transfected with 2* RATS-CAT and stained for the Ets-2 protein and the RATS
      sequence by combining immunofluorescence and fluorescence in situ hybridization
      techniques. In unstimulated cells, Ets-2 bound to RATS, whereas no binding was
      observed in stimulated cells. To test for RATS specificity, the same experiments
      were performed with 2* mutantRATS-CAT, and no binding of Ets-2 was observed. The
      results were corroborated by chromatin immunoprecipitation assays performed with
      the same cells. Our results show that Ets-2 is a transcriptional repressor of HIV
      1. Repression of HIV-LTR-RATS mediated by Ets-2 may account for the low-level
      transcription and replication of HIV-1 in naive Th-cells, and contribute to the
      viral latency and maintenance of viral reservoirs in patients, despite long-term
      therapy.

PMID- 29354131
TI  - Dynamics of CD4 and CD8 T-Cell Subsets and Inflammatory Biomarkers during Early
      and Chronic HIV Infection in Mozambican Adults.
AB  - During primary HIV infection (PHI), there is a striking cascade response of
      inflammatory cytokines and many cells of the immune system show altered
      frequencies and signs of extensive activation. These changes have been shown to
      have a relevant role in predicting disease progression; however, the challenges
      of identifying PHI have resulted in a lack of critical information about the
      dynamics of early pathogenic events. We studied soluble inflammatory biomarkers
      and changes in T-cell subsets in individuals at PHI (n = 40), chronic HIV
      infection (CHI, n = 56), and HIV-uninfected (n = 58) recruited at the Manhica
      District Hospital in Mozambique. Plasma levels of 49 biomarkers were determined
      by Luminex and ELISA. T-cell immunophenotyping was performed by multicolor flow
      cytometry. Plasma HIV viremia, CD4, and CD8 T cell counts underwent rapid
      stabilization after PHI. However, several immunological parameters, including Th1
      Th17 CD4 T cells and activation or exhaustion of CD8 T cells continued decreasing
      until more than 9 months postinfection. Importantly, no sign of immunosenescence
      was observed over the first year of HIV infection. Levels of IP-10, MCP-1, BAFF,
      sCD14, tumor necrosis factor receptor-2, and TRAIL were significantly
      overexpressed at the first month of infection and underwent a prompt decrease in
      the subsequent months while, MIG and CD27 levels began to increase 1 month after
      infection and remained overexpressed for almost 1 year postinfection. Early
      levels of soluble biomarkers were significantly associated with subsequently
      exhausted CD4 T-cells or with CD8 T-cell activation. Despite rapid immune control
      of virus replication, the stabilization of the T-cell subsets occurs months after
      viremia and CD4 count plateau, suggesting persistent immune dysfunction and
      highlighting the potential benefit of early treatment initiation that could limit
      immunological damage.

PMID- 29354133
TI  - Early Microglia Activation Precedes Photoreceptor Degeneration in a Mouse Model
      of CNGB1-Linked Retinitis Pigmentosa.
AB  - Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases
      characterized by progressive degeneration of rod and cone photoreceptors in the
      retina. In most cases, a rod-specific genetic defect results in early functional
      loss and degeneration of rods, which is followed by degeneration of cones and
      loss of daylight vision at later stages. Microglial cells, the immune cells of
      the central nervous system, are activated in retinas of RP patients and in
      several RP mouse models. However, it is still a matter of debate whether
      activated microglial cells may be responsible for the amplification of the
      typical degenerative processes. Here, we used Cngb1-/- mice, which represent a
      slow degenerative mouse model of RP, to investigate the extent of microglia
      activation in retinal degeneration. With a combination of FACS analysis,
      immunohistochemistry and gene expression analysis we established that microglia
      in the Cngb1-/- retina were already activated in an early, predegenerative stage
      of the disease. The evidence available so far suggests that early retinal
      microglia activation represents a first step in RP, which might initiate or
      accelerate photoreceptor degeneration.

PMID- 29354132
TI  - Bacterial Signaling at the Intestinal Epithelial Interface in Inflammation and
      Cancer.
AB  - The gastrointestinal (GI) tract provides a compartmentalized interface with an
      enormous repertoire of immune and metabolic activities, where the multicellular
      structure of the mucosa has acquired mechanisms to sense luminal factors, such as
      nutrients, microbes, and a variety of host-derived and microbial metabolites. The
      GI tract is colonized by a complex ecosystem of microorganisms, which have
      developed a highly coevolved relationship with the host's cellular and immune
      system. Intestinal epithelial pattern recognition receptors (PRRs) substantially
      contribute to tissue homeostasis and immune surveillance. The role of bacteria
      derived signals in intestinal epithelial homeostasis and repair has been
      addressed in mouse models deficient in PRRs and signaling adaptors. While
      critical for host physiology and the fortification of barrier function, the
      intestinal microbiota poses a considerable health challenge. Accumulating
      evidence indicates that dysbiosis is associated with the pathogenesis of numerous
      GI tract diseases, including inflammatory bowel diseases (IBD) and colorectal
      cancer (CRC). Aberrant signal integration at the epithelial cell level
      contributes to such diseases. An increased understanding of bacterial-specific
      structure recognition and signaling mechanisms at the intestinal epithelial
      interface is of great importance in the translation to future treatment
      strategies. In this review, we summarize the growing understanding of the
      regulation and function of the intestinal epithelial barrier, and discuss
      microbial signaling in the dynamic host-microbe mutualism in both health and
      disease.

PMID- 29354134
TI  - Function of miR-146a-5p in Tumor Cells As a Regulatory Switch between Cell Death
      and Angiogenesis: Macrophage Therapy Revisited.
AB  - Tumors survive and progress by evading killing mechanisms of the immune system,
      and by generating a tumor microenvironment (TME) that reprograms macrophages in
      situ to produce factors that support tumor growth, angiogenesis, and metastasis.
      We have previously shown that by blocking the translation of the enzyme inducible
      nitric oxide synthase (iNOS), miR-146a-5p inhibits nitric oxide (NO) production
      in a mouse renal carcinoma cell line (RENCA), thereby endowing RENCA cells with
      resistance to macrophage-induced cell death. Here, we expand these findings to
      the mouse colon carcinoma CT26 cell line and demonstrate that neutralizing miR
      146a-5p's activity by transfecting both RENCA and CT26 cells with its antagomir
      restored iNOS expression and NO production and enhanced susceptibility to
      macrophage-induced cell death (by 48 and 25%, respectively, p < 0.001). Moreover,
      miR-146a-5p suppression simultaneously inhibited the expression of the pro
      angiogenic protein EMMPRIN (threefolds, p < 0.001), leading to reduced MMP-9 and
      vascular endothelial growth factor secretion (twofolds and threefolds,
      respectively, p < 0.05), and reduced angiogenesis, as estimated by in vitro tube
      formation and scratch assays. When we injected tumors with pro-inflammatory
      stimulated RAW 264.7 macrophages together with i.v. injection of the miR-146a-5p
      antagomir, we found inhibited tumor growth (sixfolds, p < 0.001) and angiogenesis
      (twofolds, p < 0.01), and increased apoptosis (twofolds, p < 0.01). This
      combination therapy increased nitrites and reduced TGFbeta concentrations in
      tumor lysates, alleviated immune suppression, and allowed enhanced infiltration
      of cytotoxic CD8+ T cells. Thus, miR-146a-5p functions as a control switch
      between angiogenesis and cell death, and its neutralization can manipulate the
      crosstalk between tumor cells and macrophages and profoundly change the TME. This
      strategy can be therapeutically utilized in combination with the macrophage
      therapy approach to induce the immune system to successfully attack the tumor,
      and should be further explored as a new therapy for the treatment of cancer.

PMID- 29354137
TI  - On the Origin of the Non-brittle Rachis Trait of Domesticated Einkorn Wheat.
AB  - Einkorn and emmer wheat together with barley were among the first cereals
      domesticated by humans more than 10,000 years ago, long before durum or bread
      wheat originated. Domesticated einkorn wheat differs from its wild progenitor in
      basic morphological characters such as the grain dispersal system. This study
      identified the Non-brittle rachis 1 (btr1) and Non-brittle rachis 2 (btr2) in
      einkorn as homologous to barley. Re-sequencing of the Btr1 and Btr2 in a
      collection of 53 lines showed that a single non-synonymous amino acid
      substitution (alanine to threonine) at position 119 at btr1, is responsible for
      the non-brittle rachis trait in domesticated einkorn. Tracing this haplotype
      variation back to wild einkorn samples provides further evidence that the einkorn
      progenitor came from the Northern Levant. We show that the geographical origin of
      domesticated haplotype coincides with the non-brittle domesticated barley
      haplotypes, which suggest the non-brittle rachis phenotypes of einkorn and barley
      were fixed in same geographic area in today's South-east Turkey.

PMID- 29354136
TI  - Regulation of RIG-I Activation by K63-Linked Polyubiquitination.
AB  - RIG-I is a pattern recognition receptor and recognizes cytoplasmic viral double
      stranded RNA (dsRNA). Influenza A virus, hepatitis C virus, and several other
      pathogenic viruses are mainly recognized by RIG-I, resulting in the activation of
      the innate immune responses. The protein comprises N-terminal two caspase
      activation and recruitment domains (2CARDs), an RNA helicase domain, and the C
      terminal domain (CTD). The CTD recognizes 5'-triphosphate viral dsRNA. After
      recognition of viral dsRNA, the protein harbors K63-linked polyubiquitination
      essential for RIG-I activation. First, it was reported that TRIM25 ubiquitin
      ligase delivered K63-linked polyubiquitin moiety to the 2CARDs. The polyubiquitin
      chain stabilizes a structure called the 2CARD tetramer, in which four 2CARDs
      assemble and make a core that promotes the aggregation of the mitochondrial
      antiviral-signaling (MAVS) protein on mitochondria. MAVS aggregation then
      triggers the signal to induce the innate immune responses. However, subsequent
      studies have reported that Riplet, MEX3C, and TRIM4 ubiquitin ligases are also
      involved in K63-linked polyubiquitination and the activation of RIG-I. MEX3C and
      TRIM4 mediate polyubiquitination of the 2CARDs. By contrast, Riplet ubiquitinates
      the CTD. The physiological significance of each ubiquitin ligases has been shown
      by knockout and knockdown studies, but there appears to be contradictory to
      evidence reported in the literature. In this review, we summarize recent findings
      related to K63-linked polyubiquitination and propose a model that could reconcile
      current contradictory theories. We also discuss the physiological significance of
      the ubiquitin ligases in the immune system against viral infection.

PMID- 29354135
TI  - MicroRNA-155-at the Critical Interface of Innate and Adaptive Immunity in
      Arthritis.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that fine-tune the cell response to
      a changing environment by modulating the cell transcriptome. miR-155 is a
      multifunctional miRNA enriched in cells of the immune system and is indispensable
      for the immune response. However, when deregulated, miR-155 contributes to the
      development of chronic inflammation, autoimmunity, cancer, and fibrosis. Herein,
      we review the evidence for the pathogenic role of miR-155 in driving aberrant
      activation of the immune system in rheumatoid arthritis, and its potential as a
      disease biomarker and therapeutic target.

PMID- 29354138
TI  - Homozygote Depression in Gamete-Derived Dragon-Fruit (Hylocereus) Lines.
AB  - Putative gamete-derived progenies from two Hylocereus species, the diploid H.
      monacanthus and the tetraploid H. megalanthus, were studied with the dual aims to
      confirm their gamete origin and to evaluate their potential use as genetic
      resources. An additional goal was to determine the origin (allotetraploid vs.
      autotetraploid) of H. megalanthus by exploring morphological variations in the di
      haploid (2x) H. megalanthus progeny. Gamete origin was proved in all five H.
      monacanthus lines obtained and in 49 of the 70 H. megalanthus lines by using flow
      cytometry and simple sequence repeat (SSR) markers. The five double-haploid (2x)
      H. monacanthus lines showed low vigor and abnormal flower development, with
      malformed ovules and aborted pollen grains. Only one flower set fruit, giving
      several viable seeds. For H. megalanthus, both abnormal ovules and defective
      anthers were observed in the di-haploid (2x) and double di-haploid (4x) lines.
      Among the 46 di-haploid lines, only 14 set fruit. Another 13 di-haploid lines
      formed flower buds that abscised before anthesis or soon after pollination. The
      severe sterility of the double-haploid H. monacanthus and the reduced fertility
      of all the di-haploid and double di-haploid H. megalanthus lines can be linked to
      their reduced heterozygosity, which drastically affected the development of
      normal female and male organs. We thus concluded that chromosome doubling, as
      occurred spontaneously in the double-haploid H. monacanthus and the double di
      haploid H. megalanthus, is not sufficient to restore fertility in Hylocereus. We
      also observed very low gametoclonal variation among the di-haploid (2x) H.
      megalanthus lines, a finding that supported an autotetraploid, rather than an
      allotetraploid, origin of this species. Nonetheless, despite the above-described
      challenging limitations, these gamete-derived lines are currently being bred as
      the seed parent, offering unique possibilities for genetic research and
      additional breeding.

PMID- 29354139
TI  - Combined Metabonomic and Quantitative RT-PCR Analyses Revealed Metabolic
      Reprogramming Associated with Fusarium graminearum Resistance in Transgenic
      Arabidopsis thaliana.
AB  - Fusarium head blight disease resulting from Fusarium graminearum (FG) infection
      causes huge losses in global production of cereals and development of FG
      resistant plants is urgently needed. To understand biochemistry mechanisms for FG
      resistance, here, we have systematically investigated the plant metabolomic
      phenotypes associated with FG resistance for transgenic Arabidopsis thaliana
      expressing a class-I chitinase (Chi), a Fusarium-specific recombinant antibody
      gene (CWP2) and fused Chi-CWP2. Plant disease indices, mycotoxin levels,
      metabonomic characteristics, and expression levels of several key genes were
      measured together with their correlations. We found that A. thaliana expressing
      Chi-CWP2 showed higher FG resistance with much lower disease indices and
      mycotoxin levels than the wild-type and the plants expressing Chi or CWP2 alone.
      The combined metabonomic and quantitative RT-PCR analyses revealed that such FG
      resistance was closely associated with the promoted biosynthesis of secondary
      metabolites (phenylpropanoids, alkanoids) and organic osmolytes (proline,
      betaine, glucose, myo-inositol) together with enhanced TCA cycle and GABA shunt.
      These suggest that the concurrently enhanced biosyntheses of the shikimate
      mediated secondary metabolites and organic osmolytes be an important strategy for
      A. thaliana to develop and improve FG resistance. These findings provide
      essential biochemical information related to FG resistance which is important for
      developing FG-resistant cereals.

PMID- 29354140
TI  - Interactive Effects of CO2 Concentration and Water Regime on Stable Isotope
      Signatures, Nitrogen Assimilation and Growth in Sweet Pepper.
AB  - Sweet pepper is among the most widely cultivated horticultural crops in the
      Mediterranean basin, being frequently grown hydroponically under cover in
      combination with CO2 fertilization and water conditions ranging from optimal to
      suboptimal. The aim of this study is to develop a simple model, based on the
      analysis of plant stable isotopes in their natural abundance, gas exchange traits
      and N concentration, to assess sweet pepper growth. Plants were grown in a growth
      chamber for near 6 weeks. Two [CO2] (400 and 800 MUmol mol-1), three water
      regimes (control and mild and moderate water stress) and four genotypes were
      assayed. For each combination of genotype, [CO2] and water regime five plants
      were evaluated. Water stress applied caused significant decreases in water
      potential, net assimilation, stomatal conductance, intercellular to atmospheric
      [CO2], and significant increases in water use efficiency, leaf chlorophyll
      content and carbon isotope composition, while the relative water content, the
      osmotic potential and the content of anthocyanins did change not under stress
      compared to control conditions support this statement. Nevertheless, water regime
      affects plant growth via nitrogen assimilation, which is associated with the
      transpiration stream, particularly at high [CO2], while the lower N concentration
      caused by rising [CO2] is not associated with stomatal closure. The stable
      isotope composition of carbon, oxygen, and nitrogen (delta13C, delta18O, and
      delta15N) in plant matter are affected not only by water regime but also by
      rising [CO2]. Thus, delta18O increased probably as response to decreases in
      transpiration, while the increase in delta15N may reflect not only a lower
      stomatal conductance but a higher nitrogen demand in leaves or shifts in nitrogen
      metabolism associated with decreases in photorespiration. The way that delta13C
      explains differences in plant growth across water regimes within a given [CO2],
      seems to be mediated through its direct relationship with N accumulation in
      leaves. The changes in the profile and amount of amino acids caused by water
      stress and high [CO2] support this conclusion. However, the results do not
      support the use of delta18O as an indicator of the effect of water regime on
      plant growth.

PMID- 29354141
TI  - Plant snRNP Biogenesis: A Perspective from the Nucleolus and Cajal Bodies.
AB  - Small nuclear ribonucleoproteins (snRNPs) are protein-RNA complexes composed of
      specific snRNP-associated proteins along with small nuclear RNAs (snRNAs), which
      are non-coding RNA molecules abundant in the nucleus. snRNPs mainly function as
      core components of the spliceosome, the molecular machinery for pre-mRNA
      splicing. Thus, snRNP biogenesis is a critical issue for plants, essential for
      the determination of a cell's activity through the regulation of gene expression.
      The complex process of snRNP biogenesis is initiated by transcription of the
      snRNA in the nucleus, continues in the cytoplasm, and terminates back in the
      nucleus. Critical steps of snRNP biogenesis, such as chemical modification of the
      snRNA and snRNP maturation, occur in the nucleolus and its related sub-nuclear
      structures, Cajal bodies. In this review, I discuss roles for the nucleolus and
      Cajal bodies in snRNP biogenesis, and a possible linkage between the regulation
      of snRNP biogenesis and plant development and environmental responses.

PMID- 29354142
TI  - Morphometrics Reveals Complex and Heritable Apple Leaf Shapes.
AB  - Apple (Malus spp.) is a widely grown and valuable fruit crop. Leaf shape is
      important for flowering in apple and may also be an early indicator for other
      agriculturally valuable traits. We examined 9,000 leaves from 869 unique apple
      accessions using linear measurements and comprehensive morphometric techniques.
      We identified allometric variation as the result of differing length-to-width
      aspect ratios between accessions and species of apple. The allometric variation
      was due to variation in the width of the leaf blade, not the length. Aspect ratio
      was highly correlated with the first principal component (PC1) of morphometric
      variation quantified using elliptical Fourier descriptors (EFDs) and persistent
      homology (PH). While the primary source of variation was aspect ratio, subsequent
      PCs corresponded to complex shape variation not captured by linear measurements.
      After linking the morphometric information with over 122,000 genome-wide single
      nucleotide polymorphisms (SNPs), we found high SNP heritability values even at
      later PCs, indicating that comprehensive morphometrics can capture complex,
      heritable phenotypes. Thus, techniques such as EFDs and PH are capturing
      heritable biological variation that would be missed using linear measurements
      alone.

PMID- 29354143
TI  - Bt Jute Expressing Fused delta-Endotoxin Cry1Ab/Ac for Resistance to Lepidopteran
      Pests.
AB  - Jute (Corchorus sp.) is naturally occurring, biodegradable, lignocellulosic-long,
      silky, golden shiny fiber producing plant that has great demands globally. Paper
      and textile industries are interested in jute because of the easy availability,
      non-toxicity and high yield of cellulosic biomass produced per acre in
      cultivation. Jute is the major and most industrially used bast fiber-producing
      crop in the world and it needs protection from insect pest infestation that
      decreases its yield and quality. Single locus integration of the synthetically
      fused cry1Ab/Ac gene of Bacillus thuringiensis (Bt) in Corchorus capsularis (JRC
      321) by Agrobacterium tumefaciens-mediated shoot tip transformation provided 5
      potent Bt jute lines BT1, BT2, BT4, BT7 and BT8. These lines consistently
      expressed the Cry1Ab/Ac endotoxin ranging from 0.16 to 0.35 ng/mg of leaf, in the
      following generations (analyzed upto T4). The effect of Cry1Ab/Ac endotoxin was
      studied against 3 major Lepidopteran pests of jute- semilooper (Anomis sabulifera
      Guenee), hairy caterpillar (Spilarctia obliqua Walker) and indigo caterpillar
      (Spodoptera exigua Hubner) by detached leaf and whole plant insect bioassay on
      greenhouse-grown transgenic plants. Results confirm that larvae feeding on
      transgenic plants had lower food consumption, body size, body weight and dry
      weight of excreta compared to non-transgenic controls. Insect mortality range
      among transgenic feeders was 66-100% for semilooper and hairy caterpillar and
      87.50% for indigo caterpillar. Apart from insect resistance, the transgenic
      plants were at par with control plants in terms of agronomic parameters and fiber
      quality. Hence, these Bt jutes in the field would survive Lepidopteran pest
      infestation, minimize harmful pesticide usage and yield good quality fiber.

PMID- 29354145
TI  - Identifying Effective Design Approaches to Allocate Genotypes in Two-Phase
      Designs: A Case Study in Pelargonium zonale.
AB  - Robust phenotypic data allow adequate statistical analysis and are crucial for
      any breeding purpose. Such data is obtained from experiments laid out to best
      control local variation. Additionally, experiments frequently involve two phases,
      each contributing environmental sources of variation. For example, in a former
      experiment we conducted to evaluate production related traits in Pelargonium
      zonale, there were two consecutive phases, each performed in a different
      greenhouse. Phase one involved the propagation of the breeding strains to obtain
      the stem cutting count, and phase two involved the assessment of root formation.
      The evaluation of the former study raised questions regarding options for
      improving the experimental layout: (i) Is there a disadvantage to using exactly
      the same design in both phases? (ii) Instead of generating a separate layout for
      each phase, can the design be optimized across both phases, such that the mean
      variance of a pair-wise treatment difference (MVD) can be decreased? To answer
      these questions, alternative approaches were explored to generate two-phase
      designs either in phase-wise order (Option 1) or across phases (Option 2). In
      Option 1 we considered the scenarios (i) using in both phases the same
      experimental design and (ii) randomizing each phase separately. In Option 2, we
      considered the scenarios (iii) generating a single design with eight replicates
      and splitting these among the two phases, (iv) separating the block structure
      across phases by dummy coding, and (v) design generation with optimal alignment
      of block units in the two phases. In both options, we considered the same or
      different block structures in each phase. The designs were evaluated by the MVD
      obtained by the intra-block analysis and the joint inter-block-intra-block
      analysis. The smallest MVD was most frequently obtained for designs generated
      across phases rather than for each phase separately, in particular when both
      phases of the design were separated with a single pseudo-level. The joint
      optimization ensured that treatment concurrences were equally balanced across
      pairs, one of the prerequisites for an efficient design. The proposed alternative
      approaches can be implemented with any model-based design packages with
      facilities to formulate linear models for treatment and block structures.

PMID- 29354144
TI  - A Community-Based Culture Collection for Targeting Novel Plant Growth-Promoting
      Bacteria from the Sugarcane Microbiome.
AB  - The soil-plant ecosystem harbors an immense microbial diversity that challenges
      investigative approaches to study traits underlying plant-microbe association.
      Studies solely based on culture-dependent techniques have overlooked most
      microbial diversity. Here we describe the concomitant use of culture-dependent
      and -independent techniques to target plant-beneficial microbial groups from the
      sugarcane microbiome. The community-based culture collection (CBC) approach was
      used to access microbes from roots and stalks. The CBC recovered 399 unique
      bacteria representing 15.9% of the rhizosphere core microbiome and 61.6-65.3% of
      the endophytic core microbiomes of stalks. By cross-referencing the CBC (culture
      dependent) with the sugarcane microbiome profile (culture-independent), we
      designed a synthetic community comprised of naturally occurring highly abundant
      bacterial groups from roots and stalks, most of which has been poorly explored so
      far. We then used maize as a model to probe the abundance-based synthetic
      inoculant. We show that when inoculated in maize plants, members of the synthetic
      community efficiently colonize plant organs, displace the natural microbiota and
      dominate at 53.9% of the rhizosphere microbial abundance. As a result, inoculated
      plants increased biomass by 3.4-fold as compared to uninoculated plants. The
      results demonstrate that abundance-based synthetic inoculants can be successfully
      applied to recover beneficial plant microbes from plant microbiota.

PMID- 29354146
TI  - Comparative Genome-Wide-Association Mapping Identifies Common Loci Controlling
      Root System Architecture and Resistance to Aphanomyces euteiches in Pea.
AB  - Combining plant genetic resistance with architectural traits that are unfavorable
      to disease development is a promising strategy for reducing epidemics. However,
      few studies have identified root system architecture (RSA) traits with the
      potential to limit root disease development. Pea is a major cultivated legume
      worldwide and has a wide level of natural genetic variability for plant
      architecture. The root pathogen Aphanomyces euteiches is a major limiting factor
      of pea crop yield. This study aimed to increase the knowledge on the diversity of
      loci and candidate genes controlling RSA traits in pea and identify RSA genetic
      loci associated with resistance to A. euteiches which could be combined with
      resistance QTL in breeding. A comparative genome wide association (GWA) study of
      plant architecture and resistance to A. euteiches was conducted at the young
      plant stage in a collection of 266 pea lines contrasted for both traits. The
      collection was genotyped using 14,157 SNP markers from recent pea genomic
      resources. It was phenotyped for ten root, shoot and overall plant architecture
      traits, as well as three disease resistance traits in controlled conditions,
      using image analysis. We identified a total of 75 short-size genomic intervals
      significantly associated with plant architecture and overlapping with 46
      previously detected QTL. The major consistent intervals included plant shoot
      architecture or flowering genes (PsLE, PsTFL1) with putative pleiotropic effects
      on root architecture. A total of 11 genomic intervals were significantly
      associated with resistance to A. euteiches confirming several consistent
      previously identified major QTL. One significant SNP, mapped to the major QTL Ae
      Ps7.6, was associated with both resistance and RSA traits. At this marker, the
      resistance-enhancing allele was associated with an increased total root projected
      area, in accordance with the correlation observed between resistance and larger
      root systems in the collection. Seven additional intervals associated with plant
      architecture overlapped with GWA intervals previously identified for resistance
      to A. euteiches. This study provides innovative results about genetic
      interdependency of root disease resistance and RSA inheritance. It identifies pea
      lines, QTL, closely-linked markers and candidate genes for marker-assisted
      selection of RSA loci to reduce Aphanomyces root rot severity in future pea
      varieties.

PMID- 29354147
TI  - Selenium Accumulation Characteristics and Biofortification Potentiality in Turnip
      (Brassica rapa var. rapa) Supplied with Selenite or Selenate.
AB  - Selenium (Se) is an essential trace element for humans. About 70% of the regions
      in China, including most of the Tibetan Plateau, are faced with Se deficiency
      problems. Turnip is mainly distributed around the Tibetan Plateau and is one of
      the few local crops. In the present study, we compared the absorption and
      translocation differences of Se (IV) selenite and Se (VI) selenate in turnip. The
      results showed that Se treatment, either by soil addition (0.2-2 mg Se kg-1 dry
      soil) or by foliar spraying (50-200 mg L-1 Se), could significantly increase the
      Se concentrations in turnips, and 0.5 mg Se (IV) or Se (VI) kg-1 dry matter in
      soils could improve the biomasses of turnips. Moreover, turnip absorbed
      significantly more Se (VI) than Se (IV) at the same concentration and also
      transferred much more Se (VI) from roots to leaves. Based on the Se
      concentrations, as well as the bioconcentration factors and translocation
      coefficients, we considered that turnip might be a potential Se indicator plant.
      Subsequently, we estimated the daily Se intake for adults based on the Se
      concentrations in turnip roots. The results indicated that Se (IV) should be more
      suitable as an artificial Se fertilizer for turnips, although the levels found in
      most samples in this study could cause selenosis to humans. In addition, we also
      estimated the optimum and maximum Se concentrations for treating turnips based on
      the linear relations between Se concentrations in turnip roots and Se treatment
      concentrations. The results provided preliminary and useful information about Se
      biofortification in turnips.

PMID- 29354148
TI  - Sequevar Diversity and Virulence of Ralstonia solanacearum Phylotype I on Mayotte
      Island (Indian Ocean).
AB  - The genetic and phenotypic diversity of the Ralstonia solanacearum species
      complex, which causes bacterial wilt to Solanacae, was assessed in 140 strains
      sampled from the main vegetable production areas of the Mayotte island. Only
      phylotype I strains were identified in the five surveyed areas. The strains were
      distributed into the following 4 sequevars: I-31 (85.7%), I-18 (5.0%), I-15
      (5.7%), and I-46 (3.6%). The central area of Mayotte was the most diverse region,
      harboring 4 sequevars representing 47.1% of the collected strains. Virulence
      tests were performed under field and controlled conditions on a set of 10 tomato
      breeding line accessions and two commercial hybrid tomato cultivars. The strains
      belonging to sequevar I-31 showed the highest virulence on the tomatoes
      (pathotypes T-2 and T-3), whereas sequevars I-18, I-15, and I-46 were grouped
      into the weakly T-1 pathotype. When the tomato accessions were challenged in the
      field and growth chambers, the highest level of resistance were observed from the
      genetically related accessions Hawaii 7996, R3034, TML46, and CLN1463. These
      accessions were considered moderately to highly resistant to representative
      strains of the most virulent and prevalent sequevar (I-31). Interestingly, the
      Platinum F1 cultivar, which was recently commercialized in Mayotte for bacterial
      wilt resistance, was highly or moderately resistant to all strains. This study
      represents the first step in the rationalization of resistance deployment
      strategies against bacterial wilt-causing strains in Mayotte.

PMID- 29354149
TI  - Haplotype Variation of Flowering Time Genes of Sugar Beet and Its Wild Relatives
      and the Impact on Life Cycle Regimes.
AB  - The species Beta vulgaris encompasses wild and cultivated members with a broad
      range of phenological development. The annual life cycle is commonly found in sea
      beets (ssp. maritima) from Mediterranean environments which germinate, bolt, and
      flower within one season under long day conditions. Biennials such as the
      cultivated sugar beet (B. vulgaris ssp. vulgaris) as well as sea beets from
      northern latitudes require prolonged exposure to cold temperature over winter to
      acquire floral competence. Sugar beet is mainly cultivated for sugar production
      in Europe and is likely to have originated from sea beet. Flowering time strongly
      affects seed yield and yield potential and is thus a trait of high agronomic
      relevance. Besides environmental cues, there are complex genetic networks known
      to impact life cycle switch in flowering plants. In sugar beet, BTC1, BvBBX19,
      BvFT1, and BvFT2 are major flowering time regulators. In this study, we
      phenotyped plants from a diversity Beta panel encompassing cultivated and wild
      species from different geographical origin. Plants were grown under different day
      length regimes with and without vernalization. Haplotype analysis of BTC1,
      BvBBX19, BvFT1, and BvFT2 was performed to identify natural diversity of these
      genes and their impact on flowering. We found that accessions from northern
      latitudes flowered significantly later than those from southern latitudes. Some
      plants did not flower at all, indicating a strong impact of latitude of origin on
      life cycle. Haplotype analysis revealed a high conservation of the CCT-, REC-,
      BBX-, and PEBP-domains with regard to SNP occurrence. We identified sequence
      variation which may impact life cycle adaptation in beet. Our data endorse the
      importance of BTC1 in the domestication process of cultivated beets and
      contribute to the understanding of distribution and adaption of Beta species to
      different life cycle regimes in response to different environments. Moreover, our
      data provide a resource for haplotypes identified for the major floral regulators
      in beet.

PMID- 29354150
TI  - Genome-Wide Association Study of Seed Dormancy and the Genomic Consequences of
      Improvement Footprints in Rice (Oryza sativa L.).
AB  - Seed dormancy is an important agronomic trait affecting grain yield and quality
      because of pre-harvest germination and is influenced by both environmental and
      genetic factors. However, our knowledge of the factors controlling seed dormancy
      remains limited. To better reveal the molecular mechanism underlying this trait,
      a genome-wide association study was conducted in an indica-only population
      consisting of 453 accessions genotyped using 5,291 SNPs. Nine known and new
      significant SNPs were identified on eight chromosomes. These lead SNPs explained
      34.9% of the phenotypic variation, and four of them were designed as dCAPS
      markers in the hope of accelerating molecular breeding. Moreover, a total of 212
      candidate genes was predicted and eight candidate genes showed plant tissue
      specific expression in expression profile data from different public
      bioinformatics databases. In particular, LOC_Os03g10110, which had a maize
      homolog involved in embryo development, was identified as a candidate regulator
      for further biological function investigations. Additionally, a polymorphism
      information content ratio method was used to screen improvement footprints and 27
      selective sweeps were identified, most of which harbored domestication-related
      genes. Further studies suggested that three significant SNPs were adjacent to the
      candidate selection signals, supporting the accuracy of our genome-wide
      association study (GWAS) results. These findings show that genome-wide screening
      for selective sweeps can be used to identify new improvement-related DNA regions,
      although the phenotypes are unknown. This study enhances our knowledge of the
      genetic variation in seed dormancy, and the new dormancy-associated SNPs will
      provide real benefits in molecular breeding.

PMID- 29354151
TI  - Comparative Transcriptome and Microscopy Analyses Provide Insights into Flat
      Shape Formation in Peach (Prunus persica).
AB  - Fruit shape is an important external characteristic that consumers use to select
      preferred fruit cultivars. In peach, the flat fruit cultivars have become more
      and more popular worldwide. Genetic markers closely linking to the flat fruit
      trait have been identified and are useful for marker-assisted breeding. However,
      the cellular and genetic mechanisms underpinning flat fruit formation are still
      poorly understood. In this study, we have revealed the differences in fruit cell
      number, cell size, and in gene expression pattern between the traditional round
      fruit and modern flat fruit cultivars. Flat peach cultivars possessed
      significantly lower number of cells in the vertical axis because cell division in
      the vertical direction stopped early in the flat fruit cultivars at 15 DAFB (day
      after full bloom) than in round fruit cultivars at 35 DAFB. This resulted in the
      reduction in vertical development in the flat fruit. Significant linear
      relationship was observed between fruit vertical diameter and cell number in
      vertical axis for the four examined peach cultivars (R2 = 0.9964) at maturation
      stage, and was also observed between fruit vertical diameter and fruit weight (R2
      = 0.9605), which indicated that cell number in vertical direction contributed to
      the flat shape formation. Furthermore, in RNA-seq analysis, 4165 differentially
      expressed genes (DEGs) were detected by comparing RNA-seq data between flat and
      round peach cultivars at different fruit development stages. In contrast to
      previous studies, we discovered 28 candidate genes potentially responsible for
      the flat shape formation, including 19 located in the mapping site and 9
      downstream genes. Our study indicates that flat and round fruit shape in peach is
      primarily determined by the regulation of cell production in the vertical
      direction during early fruit development.

PMID- 29354152
TI  - Variation in the Abundance of OsHAK1 Transcript Underlies the Differential
      Salinity Tolerance of an indica and a japonica Rice Cultivar.
AB  - Salinity imposes a major constraint over the productivity of rice. A set of
      chromosome segment substitution lines (CSSLs), derived from a cross between the
      japonica type cultivar (cv.) Nipponbare (salinity sensitive) and the indica type
      cv. 9311 (moderately tolerant), was scored using a hydroponics system for their
      salinity tolerance at the seedling stage. Two of the CSSLs, which share a ~1.2
      Mbp stretch of chromosome 4 derived from cv. Nipponbare, were as sensitive to the
      stress as cv. Nipponbare itself. Fine mapping based on an F2 population bred from
      a backcross between one of these CSSLs and cv. 9311 narrowed this region to 95
      Kbp, within which only one gene (OsHAK1) exhibited a differential (lower)
      transcript abundance in cv. Nipponbare and the two CSSLs compared to in cv. 9311.
      The gene was up-regulated by exposure to salinity stress both in the root and the
      shoot, while a knockout mutant proved to be more salinity sensitive than its wild
      type with respect to its growth at both the vegetative and reproductive stages.
      Seedlings over-expressing OsHAK1 were more tolerant than wild type, displaying a
      superior photosynthetic rate, a higher leaf chlorophyll content, an enhanced
      accumulation of proline and a reduced level of lipid peroxidation. At the
      transcriptome level, the over-expression of OsHAK1 stimulated a number of stress
      responsive genes as well as four genes known to be involved in Na+ homeostasis
      and the salinity response (OsHKT1;5, OsSOS1, OsLti6a and OsLti6b). When the
      stress was applied at booting through to maturity, the OsHAK1 over-expressors out
      yielded wild type by 25%, and no negative pleiotropic effects were expressed in
      plants gown under non-saline conditions. The level of expression of OsHAK1 was
      correlated with Na+/K+ homeostasis, which implies that the gene should be
      explored a target for molecular approaches to the improvement of salinity
      tolerance in rice.

PMID- 29354153
TI  - miR156/SPL10 Modulates Lateral Root Development, Branching and Leaf Morphology in
      Arabidopsis by Silencing AGAMOUS-LIKE 79.
AB  - The developmental functions of miR156-SPL regulatory network have been
      extensively studied in Arabidopsis, but the downstream genes regulated by each
      SPL have not been well characterized. In this study, Next Generation Sequencing
      based transcriptome analysis was performed on roots of wild type (WT) and miR156
      overexpression (miR156OE) plants. One of the SPL genes, SPL10, which represses
      lateral root growth in Arabidopsis, was significantly downregulated in miR156OE
      plants. A transcription factor, AGAMOUS-like MADS box protein 79 (AGL79), was
      also significantly downregulated in the miR156OE plants, but was upregulated in
      the SPL10 overexpression (SPL10OE) Arabidopsis plants. In addition, SPL10 was
      found to bind to the core consensus SPL binding sequences in AGL79 gene.
      Moreover, analyses of complementation lines revealed a linear relationship
      between SPL10 and AGL79 in regulating Arabidopsis plant development. In addition,
      it was observed that plant phenotypes are AGL79 dose-dependent, with higher
      expression causing narrow leaf shape, less number of leaves and early flowering
      time, whereas relatively lower AGL79 overexpression produce plants with more
      rosette leaves and more lateral branches. Our findings revealed direct binding of
      SPL10 to AGL79 promoter, which further suggests a role for miR156/SPL10 module in
      plant lateral root growth by directly regulating AGL79.

PMID- 29354154
TI  - Evolutionary and Expression Analyses Show Co-option of khdrbs Genes for Origin of
      Vertebrate Brain.
AB  - Genes generated by whole genome duplications (WGD) can be co-opted by changing
      their regulation process or altering their coding proteins, which has been shown
      contributable to the emergence of vertebrate morphological novelties such as
      vertebrate cartilage. Mouse khdrbs genes, differing from its invertebrate
      orthologs, were mainly expressed in brain, hinting that khdrbs gene family as a
      member of genetic toolkit may be linked to vertebrate brain development. However,
      the evolutionary relationship between khdrbs gene family and vertebrate brain
      development is unclear. First, we analyzed the evolutionary history of khdrbs
      gene family in metazoans, and then investigated their expression patterns during
      early development and in adulthood of zebrafish. We found that the duplication of
      khdrbs gene family by WGD took place in zebrafish, and all zebrafish khdrbs genes
      were predominantly expressed in the substructures of brain during early
      development. Given the expression of invertebrate khdrbs gene in germ line, the
      distinct expression domains of zebrafish khdrbs genes in brain suggested that the
      duplicated khdrbs genes are co-opted for promoting the evolutionary origin of
      vertebrate brain.

PMID- 29354155
TI  - The effect of strontium chloride on human periodontal ligament stem cells.
AB  - The complete repair of periodontal structures remains an exciting challenge that
      prompts researchers to develop new treatments to restore the periodontium. Recent
      research has suggested strontium ion to be an attractive candidate to improve
      osteogenic activity. In this study, we have isolated a clonal finite cell line
      derived from human periodontal ligament (PDL) in order to assess whether and in
      which way different doses of SrCl2 (from 0.5 to 500 MUg/ml) can influence both
      the proliferation and the mineralization process, for future application in oral
      diseases. PDL cells were cloned by dilution plating technique and characterized
      by FACS. Cell proliferation analysis and mineralization were performed by [3H]
      thymidine incorporation and spectrofluorometric assay. Results have evidenced
      that the higher SrCl2 concentrations tested, from 25 to 500 MUg/ml, have
      increased the proliferation activity after only 24 h of treatment. Interestingly,
      the same higher concentrations have decreased the mineralization, which was
      conversely increased by the lower ones, from 0.5 to 10 MUg/ml. Our findings
      suggest the possible use of SrCl2 in appropriate delivery systems that release,
      at different time points, the specific dose, depending on the biological response
      that we want to induce on periodontal ligament stem cells, providing a more
      efficient periodontal regeneration.

PMID- 29354156
TI  - Lower limbs heterometry correction in patients with osteoporosis and increased
      risk of falls.
AB  - Osteoporotic fractures are associated with a significant increase in morbidity,
      mortality and medical costs. There is also a strong link between fractures and
      increased mortality. Among effective measures for the prevention of falls,
      instability treatment surely plays a crucial role. Several factors contribute to
      instability, many of which are ageing-related: visual spatial deficit, strength
      reduction, weight imbalance with COP lateralization sometimes favoured by LLD
      (leg length discrepancy). It seems useful to detect an heterometry which could be
      corrected, if present. The aim of our work is to assess the responses of
      individuals with heterometry diagnosis to the wedge positioning, using the
      balance board Lizard 3.0(r). In the period between January 2013 and September
      2013, 52 patients were recruited with clinical heterometry >5 mm among those that
      were treated in the Recovery and Rehabilitation Agency's postural clinic of the
      Careggi Hospital Orthopedic Trauma Centre in Florence. Our measurements have
      revealed that there is a statistically significant correlation (p<0.5) between
      clinical limb shortening expressed in mm and location of the weight imbalance at
      the stabilometric examination at T0; our data shows that the majority of patients
      with clinical heterometry shows a weight imbalance on the longer limb. After
      heterometry correction, 21 patients showed a statistically significant reduction
      (p<0,01) in weight imbalance expressed in kg between T0 and T1 and have been
      assigned to group 1, the remaining 31 worsened and have been assigned to group 2.
      From the results of our study, it is clear that the correction of lower limbs
      heterometry shouldn't be based only on clinical measuring of the limbs length
      discrepancy, even if very accurate.

PMID- 29354157
TI  - Grafting and fixation of proximal humeral aseptic non union: a prospective case
      series.
AB  - Background: Fractures of the proximal part of the humerus represent almost 4-5%
      of all fractures. The rate of non union is estimated to be 1.1 to 10%. Non union,
      displacement, and fixation failure can be hazardous complications for these
      injuries. The purpose of our study was to evaluate the outcomes of plate and bone
      strut allograft with bone chips grafting augmentation in the management of
      proximal humeral aseptic non union. Methods: We treated 16 aseptic non union
      proximal humeral fractures by the medial humeral shaft bone strut allograft and
      lateral plate and screws with bone chips grafting. The patients' ages were
      between 55 and 70 years. The chosen criteria to evaluate the group during the
      clinical and radiological follow-up were the quality of life measured by The
      Short Form (12) Health Survey (SF-12), shoulder function and related quality of
      life measured by the Constant Shoulder Score (CSS) compared with healthy side,
      bone healing measured by X-rays, and postoperative complications. The follow-up
      was perfor med with clinical and radiographic controls at 1, 3, 6 and 12 months.
      Surgical time and international units of red blood cells transfused were also
      calculated. The evaluation endpoint was set at 12 months. Results: The X-rays
      bone healing occurred in our group on average of 126.4 days after surgery. The
      surgical time and blood loss were consistent with standard surgical procedures.
      The quality of life and functional recovery were excellent after plate and bone
      strut allograft. Conclusions: Surgical techniques that increase mechanical
      stability, while incorporating bone biology, are effective aids for treating
      problematic fractural patterns.

PMID- 29354158
TI  - Effect of combined treatment with focused mechano-acoustic vibration and
      pharmacological therapy on bone mineral density and muscle strength in post
      menopausal women.
AB  - Introduction: Osteoporosis is a systemic disease of the skeleton characterized by
      a reduction in bone mass and alterations in microarchitecture accompanied by
      increase in fracture risk, with a relevant decline in quality of life and
      important social, economic, and health implications, representing one of the most
      common causes of disability and a major financial item of health cost in many
      Countries. The best therapy for osteoporosis is prevention, consisting in
      measures to avoid or slow the onset of the disease. Treatment includes measures
      aimed at osteoporotic individuals, with or without previous fractures and a high
      risk of a first or additional fracture. Method: We enrolled thirty post
      menopausal osteoporotic women, allocated in the first group underwent a 6-month
      personalized drug therapy and focused mechanoacoustic vibration (2 sessions per
      week, each lasting 15 minutes); women allocated in the second group underwent
      only 6-month personalized drug therapy. Patients were evaluated performing dual
      energy X-ray absorptiometry (DXA) and isokinetic machine evaluation, and
      administration of Tinetti scale and ECOS-16 questionnaire. Result: Show
      improvement of bone mineral density (BMD) and T-score at the lumbar spine and
      femoral neck, handgrip strength and isokinetic strength of the knee estensors,
      balance and gait, and quality of life. Conclusion: Hence, the combined treatment
      with focused mechano-acoustic vibration and pharmacological therapy has a
      beneficial effect on BMD and T-score as well as on the muscle strength and
      quality of life of osteoporotic subjects.

PMID- 29354159
TI  - Hypothyrodism as a risk factor of periodontitis and its relation with vitamin D
      deficiency: mini-review of literature and a case report.
AB  - Objective: The purpose of this report is to investigate the role and efficiency
      of the intra-ligamentary injection of vitamin D and calcium in the treatment of
      chronic periodontitis associated with hypothyroidism. Design: A 43-year-old
      female with suspected hypothyroidism who revealed severe chronic periodontitis
      with grade III mobility. Pre-operative periodontal and systemic control preceded
      the used intervention. After 3 months, intra-ligamentary injectable vitamin D
      with calcium was introduced. Results: Clinical evaluation revealed great
      improvement of the injected sites. Marked reduction of mobility, pocket depth and
      bleeding were detected. Conclusions: Injectabe vitamin D is an adjunctive
      treatment modality that needs to be discovered in another way. It may provide
      further solutions for the periodontal regeneration problem. Clinical studies with
      large sample sizes and long term follow up are needed.

PMID- 29354161
TI  - Atypical femur fractures: a distinctive tract of adult hypophosphatasia.
AB  - Hypophosphatasia (HPP) is a congenital, rare and heterogeneous bone disorder,
      characterized by a deficit of calcified tissue mineralization, leading to
      skeletal deformities and osteomalacia in adults, rickets in infants and children,
      and fragility fractures and premature loss of dentition in children and adults.
      The disease is caused by a reduced or absent expression and activity of the
      tissue non-specific alkaline phosphatase (TNSALP) enzyme, derived from
      inactivating mutations of the alkaline phosphatase (ALPL) gene. Six different
      clinical variants have been reported, defined by the onset age and characterized
      by different degrees of severity. The adult form of HPP presents a wide range of
      clinical manifestations, many of which are non-specific, mild, and often
      overlapping with other metabolic bone diseases. Consequently, many cases of adult
      HPP are, commonly, undiagnosed or misdiagnosed, and, subsequently, wrongly or non
      treated with severe consequences for patients and a very negative impact on their
      quality of life and life expectancy, as well as with costs due to the
      administration of wrong therapies and treatments of their side effects. The
      occurrence of a fragility atypical femur fracture in the adulthood can be
      suspected as a clinical indication of an undiagnosed adult mild form of HPP; and
      the presence of at least one of this kind of fracture can help in the diagnosis
      of adult HPP, together with conventional HPP biochemical signs.

PMID- 29354160
TI  - Surgical treatment of neglected hip fracture in children with cerebral palsy:
      case report and review of the literature.
AB  - Case: A clinical case of a 15-year-old cerebral palsy child with a Sandhu type 2
      neglected femoral neck fracture is presented. The patient was treated using
      cannulated screws and cancellous bone graft augmented with mesenchymal stem
      cells. At 6 months after the surgery complete fracture healing was observed.
      Conclusion: To early diagnose this fractures, it is mandatory to perform a
      comprehensive clinical and radiological evaluation including also a second level
      imaging. The use of cannulated screws with cancellous bone graft and MSCs is a
      viable treatment option in these patients.

PMID- 29354162
TI  - Pitfalls in interpreting interventional studies for osteoporosis.
AB  - After adulthood, changes in the skeleton are slow and takes years for accruing or
      losing any appreciable amount of bone mass. Proper interpretation of studies that
      evaluate the effect of nutrients (like calcium, vitamin D) and anti-resorptive
      agents (like bisphosphonates) on bone mass is important so that the true effect
      of the agent is measured correctly. In this report, we are highlighting two
      issues of utmost importance for correctly interpreting interventional studies for
      osteoporosis. One issue is the bone remodelling transient (BRT). It refers to a
      transient change in bone mineral density (BMD) by any agent that reduces
      remodeling space temporarily. This change is, however, not sustained for a long
      period and can be misinterpreted as a true gain in bone mass. The second issue is
      difference between calcium balance and bone balance. Calcium balance is the
      difference between the amount of calcium ingested in a day and the amount of
      calcium lost in that day. Recommendations for dietary calcium intake are based on
      calcium balance studies that presume calcium balance as an equivalent for bone
      balance. However, these are two different entities and need to be distinguished.
      Dietary calcium requirements should be established by bone balance studies using
      bone densitometry, not by calcium balance studies.

PMID- 29354163
TI  - Secondary aneurysmal bone cyst in McCune-Albright syndrome.
AB  - Polyostotic fibrous dysplasia in combination with cafeau-lait macules and
      hyperfunctioning endocrinopathies consists of a rare clinical condition termed as
      McCune-Albright syndrome. Aneurysmal bone cysts are tumor-like cystic lesions,
      composed of blood-filled compartments. They may occur as primary lesions or
      secondary to other pathologies; most commonly giant cell tumors of bone. However,
      secondary aneurysmal bone cysts in McCune-Albright syndrome are exceptional. We
      present a 28-year-old female with McCune-Albright syndrome. She experienced
      precocious puberty at age 3 months. In childhood, she experienced multiple long
      bone fractures, facial deformity and progressive visual and hearing impairment.
      One year ago, she experienced a painful, gradually enlarging bone lesion
      involving the right ilium, pubic and ischial bone with groundglass appearance,
      septa, marginal sclerosis, endosteal scalloping and blow-out expansion resulting
      in localized thinning of the cortex. CT-guided needle biopsy of the pelvic lesion
      showed aneurysmal bone cyst. Selective arterial embolization was recommended,
      however, the patient and her relatives did not consent to proceed to treatment,
      and she remained in close surveillance thereafter.

PMID- 29354164
TI  - Actual reason for bone fractures in the case of a patient followed-up with the
      osteogenesis imperfecta: Gaucher's Disease.
AB  - Gaucher's disease (GD) is a rare disease characterized by a beta-glucocerebroside
      accumulation in the reticulo-endothelial system. Patients may refer to the clinic
      with complaints of bone pain, hepatosplenomegaly, anemia, thrombocytopenia,
      growth retardation, interstitial pulmonary disease, pulmonary hypertension, and
      skeletal disorders. Skeletal system involvement is observed commonly in Gaucher
      patients and a significant cause of morbidity. Our patient was followed for
      several years as a glass child - osteogenesis imperfecta and he had joint
      deformities due to skeletal fractures. We wanted to present this case to raise
      awareness of GD's skeletal involvement and effects of late diagnosis.

PMID- 29354165
TI  - Calcitriol-mediated hypercalcemia secondary to granulomatous disease caused by
      soft-tissue filler injection: a case report.
AB  - Soft-tissue filler (STF) injections have been used worldwide for cosmetic
      reasons. In most cases, they are not approved by the United States Food and Drug
      Administration (FDA). Regulatory boards in Latin American countries do not allow
      the medical use of STF injections; however, these injections are still widely
      used. A case of calcitriol-mediated hypercalcemia with ectopic calcifications,
      chronic kidney disease, nephrolithiasis and calcinosis is presented. The reported
      case highlights the consequences of STF use, including calcitriol-mediated
      hypercalcemia secondary to granulomatous reactions years after an esthetic
      procedure.

PMID- 29354166
TI  - Adult-onset hypophosphatasia diagnosed following bilateral atypical femoral
      fractures in a 55-year-old woman.
AB  - We report the case of a 55-year-old woman who presented to the emergency
      department having woken from sleep with right sided thigh swelling. Pelvic
      radiographs revealed bilateral atypical subtrochanteric femoral fractures
      (ASFFs). In the two years leading up to this admission, the patient had
      experienced gradually increasing pain and weakness in her legs which had resulted
      in a decrease in her mobility from fully mobile to bed-bound. During this time a
      neurologist had organised a magnetic-resonance imaging (MRI) scan of the brain
      and spine which was normal. There was no history of bisphosphonate (BP) use.
      Historical and admission blood tests revealed a persistently low serum alkaline
      phosphatase (ALP), with all other results within normal limits. The patient was
      treated with intramedullary nailing of both femurs and histological analysis of
      bone reamings were characteristic of hypophosphatasia (HPP). The patient was
      independently mobilising with a walking frame on discharge. Subsequent genetic
      testing revealed bi-allelic pathogenic variants in the TNSALP gene: c.526G>A,
      p.(Ala176Thr) and c.1171C>T, p.(Arg391Cys). HPP is an inborn error in metabolism
      caused by mutation in the gene coding for tissue non-specific alkaline
      phosphatase (TNSALP), resulting in a decrease in serum ALP concentrations. The
      age at which it presents which can vary from childhood to middle age, with
      symptoms ranging from perinatal death to late-onset osteomalacia. In those
      patients who survive to adulthood, there is a predisposition to fractures,
      including ASFFs. Treatment with asfotase alfa (a bone-targeted, recombinant human
      TNSALP) has been approved for perinatal, infantile and paediatric-onset
      hypophosphatasia. This case emphasises the importance of viewing persistent low
      ALP as a 'red flag' in patients presenting with musculoskeletal symptoms. Timely
      diagnosis and treatment of HPP can reduce the risk of serious complications, such
      as those experienced by this patient.

PMID- 29354167
TI  - Neonatal severe hyperparathyroidism secondary to a novel homozygous CASR gene
      mutation.
AB  - Neonatal severe hyperparathyroidism (NSHPT) is a rare autosomal recessive
      disease. Children present within the first 6 months of life and more commonly in
      the first few weeks. Common presentation is poor feeding, polyuria, dehydration,
      lethargy, failure to thrive, hypotonia, gastrointestinal dysmotility, osteopenia
      and symptoms of respiratory distress due to a poorly developed chest cage. We
      present a case of a 2-month old girl with severe hypercalcemia and
      hyperparathyroidism. She was found to have a novel homozygous mutation in the
      acceptor splicing site of intron 4 (c.1378 -2A>G) of the calcium sensing receptor
      gene (CASR). This mutation causes frame shift deletion of exon 5 and
      insensitivity of CASR to calcium. The patient was treated with intravenous
      fluids, fruosemide, calcitonin, intravenous pamidronate and oral cinacalcet. She
      did not respond to medical treatment. Parathyroid gland imaging including
      ultrasound, MRI and sestamibi nuclear scan were not helpful in localizing the
      glands. Her symptoms resolved following total parathyroidectomy. She is being
      treated with alfacalcidiol and calcium supplements to maintain normal serum
      calcium and phosphate. She achieved her normal developmental milestones.

PMID- 29354168
TI  - Glomus tumor as a cause of oncogenic osteomalacia.
AB  - Many tumors that occasionally are benign in origin causes hypophosphatemic
      osteomalacia. Here we present a case of glomus tumor in a 59-year-old man with
      oncogenic osteomalacia. Diagnosis was made after observation of abnormal increase
      activity in octreotide scan. The magnetic resonance imaging showed a round lesion
      in left ankle joint. Surgical excision of tumor was curative and all symptoms and
      intractable hypophosphatemia improved after few weeks.

PMID- 29354169
TI  - Femur shaft fracture following osteoid osteoma radiofrequency ablation.
AB  - Introduction: Radiofrequency ablation is an effective modality in treating
      osteoid osteoma while avoiding the complications of an open procedure. Its
      complications are usually self-limited consisting mostly of local skin burns.
      This report presents a major complication, a femur shaft fracture following an
      osteoid osteoma radiofrequency ablation. The fracture occurred approximately one
      year after the ablation at the site of the osteoid osteoma. Discussion: Few case
      reports have been published regarding subtrochanteric femur fracture after
      ablation of an osteoid osteoma. To our knowledge this is the first report of a
      femoral shaft fracture following an ablation. Another unique characteristic of
      the presented case is the late presentation, approximately one year following
      ablation. Factors which may have contributed to the fracture include lateral
      entry point of the drill which may have weakened the femur when taking its
      biological and mechanical properties into account, and the fact that the patient
      was a soldier who was allowed to continue his military training only six weeks
      after the ablation. Conclusion: Radiofrequency ablation is an effective and
      relatively safe technique in treating osteoid osteomas, however the physician
      should be aware of the fracture risk involved, consider mechanical and biologic
      factors of the bone prior to drilling, and be very conservative when recommending
      return to high level activity. In addition, a close follow-up should be carried
      on after the procedure in order to supervise bone remodeling.

PMID- 29354170
TI  - Subtrochanteric femoral stress fracture with features of atypical femoral
      fracture in patient with Paget's disease: a case report.
AB  - Atypical femoral fracture (AFF) has been widely issued since the American Society
      for Bone and Mineral Research (ASBMR) taskforce stated a possible association
      with long-term use of bisphosphonate in 2010. ASBMR taskforce recommended to
      include Paget's disease as one of variables to investigate the AFF in 2010. On
      the other hand, the ASBMR taskforce in 2014 excluded Paget's disease in the
      definition of AFF. Still, any rationale has been barely documented about this
      change. We described the rationale by reporting an 85-year-old man who had a
      subtrochanteric fracture with features of atypical femoral fracture which turned
      out to be Paget's disease of bone in the pathology.

PMID- 29354171
TI  - The challenge of nonunion after osteosynthesis of the clavicle: is it a
      biomechanical or infection problem?
AB  - Introduction: The nonunion rate has been reported between 0.1% and 15%. There are
      also several predisposing factors for the onset of complications: general factors
      connected with the patient and specific factors related to the fracture site. The
      purpose of our study is to review the etiology of nonunion of the clavicle in its
      atrophic form and investigate the outcomes of the revision treatment in a single
      step. Materials and methods: Retrospective study on 71 patients suffering from
      nonunions due to the following treatments: conservative in 13 patients; plate
      fixation in 12; closed reduction and fixation with K-wire in 24; open reduction
      and fixation with K-wire. All patients were operated on in beach chair position
      and classic approach to the clavicle by incising the previous surgical scar. The
      clinical and radiographic criteria for evaluating the outcomes were: the Short
      Form (12) Health Survey (SF-12), the Constant Shoulder Score (CSS) and the
      Disability Disabilities of the Arm, Shoulder and Score (DASH) and radiographic
      Union Score (RUS) for bone healing. The evaluation endpoint was set at 12 months.
      Results: Blood and culture tests showed 22 infected nonunions and 49 atrophic or
      oligoatrophic. In only 10 cases, before surgery, the inflammatory markers were
      positive. The isolated microorganisms were resistant to common antibiotics. In 70
      out of 71 cases, plates and screws on the upper side and fibula allogenic splints
      at the bottom, associated with cancellous bone grafts taken from the patients'
      iliac crests, were implanted. In one case, however, it was decided to implant the
      plate on the front edge of the clavicle and the fibula allogeneic splint on the
      posterior margin, also associated with a cancellous bone graft taken from the
      patient's iliac crest. The radiographic bone healing was observed in 107.8 (range
      82-160) days for the aseptic nonunions, while in 118.4 (range 82-203) days for
      the septic ones. The non-healing case was a serious failure that led to asubtotal
      excision of the clavicle. Conclusions: The importance of classification and study
      of nonunions are essential to achieve positive outcomes. The guiding principle of
      our work is that aseptic nonunions heal in the operating room, while infected
      nonunions can be challenged and defeated on the operating table. Restoring the
      correct length of the clavicle interconnection between the sternum and the
      shoulder cingulum is indispensable to avoid functional deficits of the upper
      limb. The fibula splint and the tricorticale bone graft have both mechanical and
      strong biological values to quickly heal the nonunion. The return to pre-injury
      quality of life has to be our main goal.

PMID- 29354172
TI  - Transcatheter aortic valve implantation at a high-volume center: the Bad
      Rothenfelde experience.
AB  - Introduction: The "transfemoral (TF) first" approach to access route selection in
      transcatheter aortic valve implantation (TAVI) is popular; however, the risk of
      major vascular complications is substantial. The "best for TF" approach
      identifies only the patients with ideal anatomy for TF-TAVI, potentially
      minimizing complications. Aim: To characterize the outcomes of patients
      undergoing TAVI at a large-volume site that employs this approach. Material and
      methods: Patients who underwent TAVI at the Bad Rothenfelde Heart Centre between
      2008 and 2016 were consecutively enrolled. Findings were compared to those from
      large, multicenter registries. Results: Of the 1,644 patients enrolled, 1,140
      underwent TA- and 504 TF-TAVI. Comorbidities were more frequent in TA patients,
      who also had higher risk scores (EuroSCORE: 25.5% vs. 21.2%; STS score: 11.0% vs.
      7.5%; p < 0.001 for both). Rates of conversion to open surgery, major vascular
      complications and intra-procedural mortality did not differ between groups. At 30
      days, mortality rates were higher in the TA group (3.9% vs. 1.9%, p = 0.036).
      Stroke/transient ischemic attack and permanent pacemaker implantation rates did
      not differ significantly between groups (2.0% and 9.1% overall, respectively).
      Compared to multicenter registries, trends in mortality and complication rates
      were similar, though magnitudes were lower in the present study. In contrast with
      the present study, major vascular complication rates in multicenter registries
      are significantly higher for TF compared to TA patients. Conclusions: At this
      high-volume center, the use of a "best for TF" approach to TAVI resulted in low
      mortality and complication rates.

PMID- 29354173
TI  - Pulmonary carcinoids - analysis of early and long-term surgical treatment
      outcomes in a group of 90 patients.
AB  - Introduction: Over the years, pulmonary carcinoids have been treated as locally
      malignant tumors because of the favorable prognosis. It is currently known that
      the clinical course of the disease is mainly dependent on the carcinoid subtype.
      Aim: To analyze the early and long-term surgical treatment outcomes for typical
      and atypical carcinoids. Material and methods: A total of 90 patients were
      treated surgically for pulmonary carcinoid tumors in the years 2007-2015. Typical
      carcinoids were diagnosed in 69 (77%) cases, while atypical carcinoids - in 21
      (23%); 67 patients underwent lobectomy, 3 - sleeve lobectomy, 9 - bilobectomy, 2 
      pneumonectomy, 1 - segmentectomy, and 8 - wedge resection. Results: None of the
      patients died in the postoperative period. Complications occurred in 14.4% of
      patients. The most common complications included: arrhythmias (5.6%), prolonged
      air leak (3.3%), and residual pneumothorax (3.3%). Among the 21 patients with
      atypical carcinoids, N1 metastasis was found in 1 (4.8%) patient, while N2 - in 5
      (23.8%) patients. In the group of 69 patients with typical carcinoids, N1
      metastasis was revealed in 7 (10.1%) patients and N2 metastases - in 2 (2.9%)
      patients. The probability of 5-year survival in patients with typical and
      atypical carcinoids was 96% and 83%, respectively. During the follow-up period 7
      (7.8%) patients, including 6 with atypical carcinoids, experienced local
      recurrence; distant metastasis occurred in 8 (8.9%) cases, including 6 with
      atypical carcinoids. Conclusions: Although radical surgical treatment provides
      excellent long-term outcomes, it should be noted that patients with pulmonary
      carcinoids (especially with the atypical subtype) may experience local recurrence
      and distant metastases even many years after surgery.

PMID- 29354174
TI  - Prometheus therapy for the treatment of acute liver failure in patients after
      cardiac surgery.
AB  - Introduction: Acute liver failure usually develops in multiple organ dysfunction
      syndrome and significantly increases the mortality risk in patients after cardiac
      surgery. Aim: To assess the safety and efficacy of extracorporeal liver support
      in patients with acute liver failure after cardiac surgery. Material and methods:
      We studied 39 adult patients with multiple organ dysfunction syndrome and acute
      liver failure as postoperative complication, treated with Prometheus therapy.
      Inclusion criteria comprised clinical and laboratory signs of acute liver
      failure. Criteria to start Prometheus therapies were: serum bilirubin above 180
      umol/l (reference values: 3-17 umol/l), hepatocyte cytolysis syndrome (at least 2
      fold increase in aspartate aminotranspherase and alanine aminotranspherase
      concentrations; reference values 10-40 U/l) and decrease in plasma cholinesterase
      (reference values 4490-13 320 U/l). Results: Extracorporeal therapy provided
      stabilization of hemodynamics, decrease in serum total bilirubin and unconjugated
      bilirubin levels, decrease in cytolysis syndrome severity and positive effect on
      the synthetic function of the liver. The 28-day survival rate in the group
      treated with Prometheus therapy was 23%. Conclusions: Prometheus procedures could
      be recommended as a part of combined intensive care in patients with acute liver
      failure after cardiac and major vessel surgery. The efficiency of this method
      could be improved by a multi-factor evaluation of patient condition in order to
      determine indications for its use.

PMID- 29354175
TI  - Open lung biopsy performed in idiopathic pulmonary fibrosis is a safe procedure.
AB  - Introduction: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease
      with a fatal prognosis. The diagnosis is made on the basis of high-resolution
      computed tomography and histological examination in selected cases. Aim: To
      determine the risk of complications of open lung biopsy performed in patients
      with IPF. Material and methods: We performed a retrospective analysis of 51
      patients who underwent diagnostic excision of pulmonary parenchyma due to IPF in
      the period 1995-2014. We assessed the complication rate, length of drainage,
      postoperative period and 30-day mortality. We compared the results of treatment
      in the groups of patients operated on with thoracotomy and videothoracoscopy.
      Results: The mean age of patients was 58 (47% female, 53% male) forced vital
      capacity (FVC) was 81%, forced expiratory volume in 1 s (FEV1) was 80% and body
      mass index (BMI) was 27 kg/m2. Thoracotomies (lateral, muscle sparing or
      anterior) were performed in 20 patients between 1995 and 2012 and
      videothoracoscopy in 31 patients operated on in the years 2009-2014. Patients in
      study groups did not differ considering age (p = 0.40), gender (p = 0.81), FVC (p
      = 0.08), FEV1 (p = 0.13) or BMI (p = 0.75). Postoperative complications occurred
      in 3.9% of patients (atrial arrhythmia 1.9% and recurrent pneumothorax 1.9%) with
      equal incidence in both study groups (p = 0.75). Median stay after thoracotomy
      was 4 days while after videothoracoscopy it was 3 days (p = 0.04). Conclusions:
      Open lung biopsy performed on patients with IPF is a safe procedure. Open lung
      biopsy performed through thoracotomy could be as safe as through VATS, however is
      characterized by longer postoperative stay.

PMID- 29354176
TI  - Outcome of surgical embolectomy in patients with massive pulmonary embolism with
      and without cardiopulmonary resuscitation.
AB  - Introduction: Pulmonary embolism is a challenging critical cardiovascular disease
      with high morbidity and mortality. Surgical embolectomy has favorable results in
      patients with massive pulmonary embolism. Aim: To study the outcome of
      embolectomy in patients with massive pulmonary embolism. Material and methods: In
      this single-center, retrospective study, 36 patients including 14 male and 22
      female patients with a mean age of 50.80 +/-18.89 years with acute pulmonary
      embolism who underwent surgical pulmonary embolectomy from January 2011 to
      January 2016 were included. The medical records of all patients were reviewed for
      demographic and preoperative data and postoperative outcomes. Results: Common
      risk factors for acute PE were major surgery within 3 months and deep vein
      thrombosis. The most common presenting symptoms of patients were dyspnea,
      followed by chest pain and syncope. Mean duration of hospitalization was 14.76 +/
      8.69 days and mean operation duration was 4.47 +/-1.54 h. Mean time from
      admission to embolectomy was 6.58 +/-1.13 h. Ten (27.8%) patients died during the
      operation including 3 cases with cardiopulmonary resuscitation prior to surgery
      and 2 cases with severe cardiogenic shock. Patients who survived were followed
      for 6 months. The mortality rate during follow-up was 15.4%; all 4 patients died
      during follow-up period due to metastatic cancer. No pulmonary embolism
      recurrance were seen. Conclusions: Although surgical embolectomy mostly was done
      for high risk patients, it had good in-hospital and excellent mid-term outcomes.

PMID- 29354177
TI  - The influence of adding tomato extract and acetylsalicylic acid to hypotensive
      therapy on the daily blood pressure profiles of patients with arterial
      hypertension and high cardiovascular risk.
AB  - Introduction: Arterial hypertension (HT) is one of the most common diseases
      around the world and constitutes a significant medical, social, and economic
      problem. Lifestyle changes, including adequate fruit and vegetable consumption,
      play an important role in controlling blood pressure (BP) and other
      cardiovascular risk factors. Aim: To compare the influence of adding
      acetylsalicylic acid (ASA) or standardized tomato extract (STE) to standard
      hypotensive therapy on the values of arterial pressure and the daily blood
      pressure profiles of patients with hypertension and high cardiovascular risk.
      Material and methods: The study included 65 patients with arterial hypertension
      and high cardiovascular risk. High-risk patients with primary hypertension were
      randomly allocated in a blinded fashion to one of two groups (ASA or STE). In
      each case, two visits were made: the first - before the treatment, and the second
      - after 4 weeks of treatment. During each visit, the patients underwent a
      clinical measurement of arterial pressure and an ambulatory blood pressure
      measurement (ABPM). Blood platelet aggregation was assessed using the VerifyNow
      analyzer. Results: After 4 weeks of treatment, the blood pressure values during
      the day (p < 0.001), during the night (p < 0.05), and in 24-h BP profiles (p <
      0.01) obtained with ABPM were significantly lower in the STE group in comparison
      to the ASA group. The addition of STE to standard hypotensive treatment resulted
      in a favorable increase in the nocturnal fall of diastolic blood pressure (DBP)
      (by 6.5%) and mean arterial pressure (MAP) (by 3.3%). Conclusions: The use of STE
      is significant in HT patients with high total cardiovascular risk; it is
      associated with better BP control and improvements in the daily BP profile.

PMID- 29354178
TI  - The role of extracorporeal membrane oxygenation in patients after irreversible
      cardiac arrest as potential organ donors.
AB  - The number of people waiting for a kidney or liver transplant is growing
      systematically. Due to the latest advances in transplantation, persons after
      irreversible cardiac arrest and confirmation of death have become potential organ
      donors. It is estimated that they may increase the number of donations by more
      than 40%. However, without good organization and communication between pre
      hospital care providers, emergency departments, intensive care units and
      transplantation units, it is almost impossible to save the organs of potential
      donors in good condition. Various systems, including extracorporeal membrane
      oxygenation (ECMO), supporting perfusion of organs for transplantation play a key
      role. In 2016 the "ECMO for Greater Poland" program was established. Although its
      main goal is to improve the survival rate of patients suffering from life
      threatening cardiopulmonary conditions, one of its branches aims to increase the
      donation rate in patients with irreversible cardiac arrest. In this review, the
      role of ECMO in the latter group as the potential organ donors is presented.

PMID- 29354179
TI  - The significance of neonatal thymectomy for shaping the immune system in children
      with congenital heart defects.
AB  - The thymus plays an important role in the development of the immune cell pool; it
      serves as the primary location for T-lymphocyte maturation. Early cardiac
      surgical interventions for congenital heart defects are necessarily associated
      with thymectomy, i.e. the partial or complete removal of the thymus. A newborn
      infant already has a functioning thymus and developed cells of the immune system.
      However, thymectomy eliminates the primary location where T cells differentiate
      and mature. This study summarizes the current knowledge of the cellular
      disturbances and potential clinical consequences associated with performing
      thymectomy in children treated surgically for congenital heart defects.

PMID- 29354181
TI  - "All in" or "Rien ne va plus"? First simultaneous catheter-based trivalvular
      treatment combined with atrial septal closure in a human.

PMID- 29354180
TI  - Malignant mesothelioma as a difficult interdisciplinary problem.
AB  - The authors of the present report review the etiology and clinical symptoms of
      malignant pleural mesothelioma (MPM) as well as diagnostic techniques (both
      radiological and biomarkers) used for its detection. Subsequently, they present
      methods of multimodal treatment (surgery, chemotherapy, and radiotherapy)
      recommended by the International Mesothelioma Interest Group (IMIG). Finally,
      they discuss complications and long-term results associated with these methods of
      MPM treatment.

PMID- 29354182
TI  - Heart transplantation in the treatment of primary non-operable cardiac tumors.

PMID- 29354183
TI  - Agenesis of right and existence of left inferior vena cava associated with
      posterior nutcracker syndrome.

PMID- 29354184
TI  - Giant hemangioma of anterior mediastinum mimicking bilateral pleural effusion.

PMID- 29354186
TI  - Professor Aleksy Ponizynski (1928-2017).

PMID- 29354185
TI  - Professor Miroslawa Narkiewicz (1931-2017) - biographical note.

PMID- 29354187
TI  - MEASURING EVERYDAY RACIAL/ETHNIC DISCRIMINATION IN HEALTH SURVEYS: How Best to
      Ask the Questions, in One or Two Stages, Across Multiple Racial/Ethnic Groups?
AB  - While it is clear that self-reported racial/ethnic discrimination is related to
      illness, there are challenges in measuring self-reported discrimination or unfair
      treatment. In the present study, we evaluate the psychometric properties of a
      self-reported instrument across racial/ ethnic groups in a population-based
      sample, and we test and interpret findings from applying two different widely
      used approaches to asking about discrimination and unfair treatment. Even though
      we found that the subset of items we tested tap into a single underlying concept,
      we also found that different groups are more likely to report on different
      aspects of discrimination. Whether race is mentioned in the survey question
      affects both frequency and mean scores of reports of racial/ethnic
      discrimination. Our findings suggest caution to researchers when comparing
      studies that have used different approaches to measure racial/ethnic
      discrimination and allow us to suggest practical empirical guidelines for
      measuring and analyzing racial/ethnic discrimination. No less important, we have
      developed a self-reported measure of recent racial/ethnic discrimination that
      functions well in a range of different racial/ethnic groups and makes it possible
      to compare how racial/ethnic discrimination is associated with health disparities
      among multiple racial/ethnic groups.

PMID- 29354188
TI  - The impact of transactional sex with teachers on public school students in
      Monrovia, Liberia - a brief report.
AB  - Access to education has been shown to strongly influence adolescent health across
      the world, and strong relationships with teachers has been found to lead to
      better academic and psychosocial outcomes for students. In many low-income
      countries where adolescents have less access to education and are more likely to
      experience poor health outcomes, risky sexual behaviors can exacerbate these
      challenges by increasing the risk of unintended pregnancy and sexually
      transmitted infections. This study sought to examine risky behaviors, such as
      substance use and risky sexual practices, of in-school youth in Liberia, a
      country in West Africa. Nine focus groups were conducted with public school
      students in Monrovia, Liberia in April 2012 using a semi-structured guide. The
      sessions took place in three public schools with n = 72 participants aged 12-20
      years old. Following thematic content analysis, a pattern emerged of
      transactional sex between female students and male teachers, which often led to
      contrived and coercive relationships for the students. Conversely, participants
      reported that educators were not disciplined for having sex with students.
      Interventions to reduce the prevalence of transactional sex within the academic
      environment would likely protect the well being of school-going youth,
      particularly female youth, and support students' academic pursuits in Liberia.

PMID- 29354189
TI  - Integration of multi-omics data for integrative gene regulatory network
      inference.
AB  - Gene regulatory networks provide comprehensive insights and indepth understanding
      of complex biological processes. The molecular interactions of gene regulatory
      networks are inferred from a single type of genomic data, e.g., gene expression
      data in most research. However, gene expression is a product of sequential
      interactions of multiple biological processes, such as DNA sequence variations,
      copy number variations, histone modifications, transcription factors, and DNA
      methylations. The recent rapid advances of high-throughput omics technologies
      enable one to measure multiple types of omics data, called 'multi-omics data',
      that represent the various biological processes. In this paper, we propose an
      Integrative Gene Regulatory Network inference method (iGRN) that incorporates
      multi-omics data and their interactions in gene regulatory networks. In addition
      to gene expressions, copy number variations and DNA methylations were considered
      for multi-omics data in this paper. The intensive experiments were carried out
      with simulation data, where iGRN's capability that infers the integrative gene
      regulatory network is assessed. Through the experiments, iGRN shows its better
      performance on model representation and interpretation than other integrative
      methods in gene regulatory network inference. iGRN was also applied to a human
      brain dataset of psychiatric disorders, and the biological network of psychiatric
      disorders was analysed.

PMID- 29354190
TI  - Sharing Individual-Level Health Research Data: Experiences, Challenges and a
      Research Agenda.
AB  - Since January 2016, the Mahidol Oxford Tropical Medicine Research Unit (MORU) has
      trialled a data-sharing policy where requests to access research datasets are
      processed through a Data Access Committee. In this paper, we share our
      experiences establishing data management systems and data-sharing infrastructure
      including a data-sharing policy, data access committee and related procedures. We
      identified a number of practical and ethical challenges including requests for
      datasets collected without specific or broad consent to data sharing and requests
      from pharmaceutical companies for data to support drug registration applications.
      We also encountered significant resource constraints which required the
      development of appropriate human resources and infrastructure. We suggest a
      research agenda to promote responsible and equitable data sharing while
      safeguarding the rights and interests of research participants and researchers.

PMID- 29354191
TI  - MEASUREMENT OF ENERGY EXPENDITURE WHILE PLAYING EXERGAMES AT A SELF-SELECTED
      INTENSITY.
AB  - Exergames have been suggested as a possible alternative to traditional exercise
      in the general population. The purpose of this study was to examine the heart
      rate (HR) and energy expenditure (EE) of young adults playing several different
      exergames, while self-selecting the component of the game to play and the
      intensity. A total of 117 participants, 18-35 years of age, were evaluated on one
      of four active video games. Participants were free to choose any component of the
      given game to play and they played at a self-selected intensity. The average HR
      and EE during the individual games were compared to resting conditions and to the
      American College of Sports Medicine (ACSM) guidelines. The HR and EE increased
      above resting conditions during each game (p<0.05). When the results of all games
      were combined, the HR was 125.4 +/- 20.0 bpm and the average EE was 6.7 +/- 2.1
      kcal/min. This HR represents an average percent of heart rate reserve of 44.6 +/-
      14.1, high enough to be considered moderate intensity exercise. If performed for
      30 minutes a day, five days per week, the average EE would be 1,005 kcals, enough
      to meet the ACSM recommendations for weekly EE. Therefore, at least some
      exergames could be a component of an exercise program.

PMID- 29354192
TI  - Canada 150.

PMID- 29354193
TI  - Can a two-hour lecture by a pharmacist improve the quality of prescriptions in a
      pediatric hospital? A retrospective cohort study.
AB  - Background: A high rate of prescription errors exists in pediatric teaching
      hospitals, especially during initial training. Objectives: To determine the
      effectiveness of a two-hour lecture by a pharmacist on rates of prescription
      errors and quality of prescriptions. Methods: A two-hour lecture led by a
      pharmacist was provided to 11 junior pediatric residents (PGY-1) as part of a one
      month immersion program. A control group included 15 residents without the
      intervention. We reviewed charts to analyze the first 50 prescriptions of each
      resident. Results: Data were collected from 1300 prescriptions involving 451
      patients, 550 in the intervention group and 750 in the control group. The rate of
      prescription errors in the intervention group was 9.6% compared to 11.3% in the
      control group (p=0.32), affecting 106 patients. Statistically significant
      differences between both groups were prescriptions with unwritten doses (p=0.01)
      and errors involving overdosing (p=0.04). We identified many errors as well as
      issues surrounding quality of prescriptions. Conclusion: We found a 10.6%
      prescription error rate. This two-hour lecture seems insufficient to reduce
      prescription errors among junior pediatric residents. This study highlights the
      most frequent types of errors and prescription quality issues that should be
      targeted by future educational interventions.

PMID- 29354194
TI  - Canadian residents' perceptions of cross-cultural care training in graduate
      medical school.
AB  - Background: The Royal College of Physicians and Surgeons of Canada specifies both
      respect for diversity as a requirement of professionalism and culturally
      sensitive provision of medical care. The purpose of the present study was to
      evaluate the perception of preparedness and attitudes of medical residents to
      deliver cross-cultural care. Methods: The Cross Cultural Care Survey was sent via
      e-mail to all Faculty of Medicine residents (approx. 450) in an academic health
      sciences centre. Comparisons were made between psychiatry residents, family
      medicine residents, and other residency groups with respect to training,
      preparedness, and skillfulness in delivering cross-cultural care. Results:
      Seventy-three (16%) residents responded to the survey. Residents in psychiatry
      and family medicine reported significantly more training and formal evaluation
      regarding cross-cultural care than residents in other programs. However, there
      were no significant differences in self-reported preparedness and skillfulness.
      Residents in family medicine were more likely to report needing more practical
      experience working with diverse groups. Psychiatry residents were less likely to
      report inadequate cross-cultural training. Conclusion: While most residents
      reported feeling skillful and prepared to work with culturally diverse groups,
      they report receiving little additional instruction or formal evaluation on this
      topic, particularly in programs other than psychiatry and family medicine.

PMID- 29354195
TI  - Senior medical students' awareness of radiation risks from common diagnostic
      imaging examinations.
AB  - Background: Senior medical students represent future physicians who commonly
      refer patients for diagnostic imaging studies that may involve ionizing
      radiation. The radiology curriculum at the University of British Columbia
      provides students with broad-based knowledge about common imaging examinations.
      The purpose of this study was to investigate students' awareness of radiation
      exposures and risks. Methods: An anonymous multiple-choice cross-sectional
      questionnaire was distributed to final year medical students to assess knowledge
      of radiation from common diagnostic examinations and radiation-related risks
      following completion of the longitudinal radiology curriculum, carried out over
      the four years of medical training. Results: Sixty-three of 192 eligible students
      participated (33% response rate). The majority felt that knowledge of radiation
      doses of common imaging examinations is somewhat or very important; however, only
      12% (N = 8) routinely discuss radiation-related risks with patients. While all
      respondents recognized children as most sensitive to the effects of radiation,
      only 24% (N = 15) correctly identified gonads as the most radiation-sensitive
      tissue. Almost all respondents recognized ultrasound and MRI as radiation free
      modalities. Respondents who correctly identified the relative dose of common
      imaging examinations in chest x-ray equivalents varied from 3-77% (N = 2 - 49);
      the remaining responses were largely underestimates. Finally, 44% (N = 28)
      correctly identified the excess risk of a fatal cancer from an abdominal CT in an
      adult, while the remainder underestimated this risk. Conclusion: Medical students
      acknowledge the importance of radiation-related issues to patient care. While
      almost all students are familiar with radiation-free modalities, many are not
      familiar with, and commonly underestimate, the relative doses and risks of common
      imaging studies. This may expose patients to increasing imaging investigations
      and exposure to radiation hazards.

PMID- 29354196
TI  - National survey of mentorship in Canadian general surgery residency programs:
      Where are we and what do we need?
AB  - Background: The benefits of mentorship on residents are well established. The
      current state of mentorship in General Surgery (GS) residency programs in Canada
      is unknown. The objectives of this study were to obtain GS residents' and program
      directors' (PD) perspectives on resident mentorship. Study Design: An electronic
      survey was developed and distributed to all 601 GS residents in Canada. All 17
      PDs were invited for telephone interviews. Results: A total of 179 of the 601
      residents responded. Ninety-seven percent (n=173) felt mentorship was important.
      Only 67% (n=116) identified a mentor and only 53% (n=62) reported a mentorship
      program. Most who identified a mentor (n=87/110, 79%) were satisfied with the
      mentorship received. Significant variations in mentorship existed between
      demographic subgroups and mentorship program types. Overall, residents (n=121,
      74%) favoured having a required mentorship program.A total of 11 out of 17 PDs
      participated in the telephone interviews. The majority of PDs (n=9, 82%) were
      satisfied with current resident mentorship but most acknowledged that barriers
      exist (n=8, 73%). Conclusion: GS programs in Canada should ensure they are
      providing equal opportunities for mentorship across demographic subgroups.
      Programs are encouraged to examine both their program's and their residents'
      needs as well as local barriers to improve mentorship.

PMID- 29354197
TI  - Students' satisfaction with general practitioners' feedback to their reflective
      writing: a randomized controlled trial.
AB  - Background: Reflective Writing (RW) is increasingly being implemented in medical
      education. Feedback to students' reflective writing (RW) is essential, but
      resources for individualized feedback often lack. We aimed to determine whether
      general practitioners (GPs) teaching students clinical skills could also provide
      feedback to RW and whether an instruction letter specific to RW feedback
      increases students' satisfaction. Methods: GPs were randomized to the two study
      arms using block randomization. GPs in both groups received an instruction letter
      on giving students feedback on clinical skills. Additionally, intervention group
      GPs received specific instructions on providing feedback to students' RW.
      Students completed satisfaction questionnaires on feedback received on clinical
      skills and RW. T-tests were employed for all statistical analysis to compare
      groups. Results: Eighty-three out of 134 physicians participated: 38 were
      randomized to the control, 45 to the intervention group. Students were very
      satisfied with the feedback on RW and clinical skills regardless of tutors' group
      allocation. A specific instruction letter had no additional effect on students'
      satisfaction. Conclusion: Based on student satisfaction, GPs who give students
      feedback on clinical skills are also well suited to provide feedback on RW. This
      approach can facilitate the introduction of mandatory RW into the regular medical
      curriculum.

PMID- 29354198
TI  - The virtual hallway consult as an effective means of continuing professional
      development in physiatry.
AB  - Background: A personal learning project (PLP) is an accredited form of Continuing
      Professional Development (CPD) in Canada, and is a self-initiated learning
      activity that is stimulated by a question, issue or dilemma in one's professional
      practice. Many complex cases or issues have no answers that are readily
      available. Many physicians rely day to day on other physician colleagues that
      they may consult in their institution. Given the paucity of same specialty
      Physical Medicine and Rehabilitation colleagues in Canadian centres, the idea of
      Virtual Spinal Cord Injury (SCI) Hallway germinated, to provide a simple tool to
      extend our hallways to reach colleagues with similar interests across the
      country. Methods: The Virtual SCI Hallway is a service set up on Yahoo Groups,
      with no cost to the users. On this invite-only site, members may post a question,
      and then all members receive the post by email. Any member may respond. Results:
      The SCI Hallway has been running successfully for over 13 years. As of January
      2017, there were 38 members, with 2124 messages within approximately 324
      conversations. Activity has been consistent since 2003. Questions and posts are
      not always medical expert related; there are also advocacy, professional, and
      scholar-role related posts. Discussion: Communication amongst specialists about
      practice and management of complicated problems is important for CPD, yet is
      difficult in subspecialized areas of medicine. Although there are many chat-pages
      in different areas of medicine on the internet, to our knowledge, there is not
      another secure, invite-only site that is low-maintenance and no cost.

PMID- 29354199
TI  - A needs assessment on addressing environmental health issues within reproductive
      health service provision: Considerations for continuing education and support.
AB  - Background: This needs assessment was initially undertaken to explore the beliefs
      and knowledge of nurses and physicians about the impact of environmental
      toxicants on maternal and infant health, as well as to describe current practice
      and needs related to addressing environmental health issues (EHI). Methods: One
      hundred and thirty-five nurses (n = 99) and physicians (n = 36) working in
      Saskatchewan completed an online survey. Survey questions were designed to
      determine how physicians and nurses think about and incorporate environmental
      health issues into their practice and means of increasing their capacity to do
      so. Results: Although participants considered it important to address EHIs with
      patients, in actual practice they do so with only moderate frequency.
      Participants reported low levels of knowledge about EHIs' impact on health, and
      low levels of confidence discussing them with patients. Participants requested
      additional information on EHIs, especially in the form of online resources.
      Conclusion: The results suggests that while nurses and physicians consider EHIs
      important to address with patients, more education, support, and resources would
      increase their capacity to do so effectively. Based on the findings,
      considerations and recommendations for continuing education in this area have
      been provided.

PMID- 29354200
TI  - Perceptions, practice, and "ownership:" experiences in continuity of the patient
      doctor relationship in a family medicine residency.
AB  - Background: The objective of this mixed-methods study was to determine
      interpersonal continuity (the ongoing therapeutic relationship between patient
      and health care provider) experiences of family medicine residents and
      preceptors, and explore their perceptions of interpersonal continuity. Methods:
      Quantitative data on resident and preceptor encounters were extracted from the
      electronic medical record (EMR). Opportunities for developing interpersonal
      continuity were determined using the Usual Provider Continuity (UPC) Index. A
      qualitative descriptive research method was used for the qualitative portion.
      Semi-structured interviews were conducted and constant comparative analysis was
      used to determine emerging themes. Results: Residents were found to have low UPC
      rates; preceptor rates were higher. Qualitative findings showed variable
      experiences with interpersonal continuity not apparent from UPC rates. Both
      preceptors and residents expressed perception of "ownership" of patients as a
      significant barrier to interpersonal continuity. Conclusion: This study suggests
      that a perceived lack of individual "ownership" of a patient panel was a
      significant barrier to developing interpersonal continuity. This might conflict
      with current changes towards team-based health care delivery. Understanding
      perceptions and changing them through a multi-faceted approach including resident
      teaching and faculty development might help improve interpersonal continuity
      which are core to both family medicine curricula and current models of health
      care delivery.

PMID- 29354201
TI  - Evaluating pediatrics residents' ethics learning needs using multisource
      interprofessional feedback.
AB  - Background: Ethics education is a required component of pediatric residency
      training. Limited instructional time requires educators to identify and
      prioritize learning needs. This is the first study to identify pediatric
      residents' ethics learning needs using a multisource (360 degree) assessment. We
      hypothesized that pediatricians or allied health care professionals would
      identify unperceived ethics learning needs. Methods: Pediatric residents,
      pediatricians, respiratory therapists (RTs), and registered nurses (RNs) working
      at a university children's hospital rated the importance of twelve ethics themes
      as learning needs for trainees using a Likert-type scale. One-way ANOVA was used
      to determine differences between the groups, followed by post-hoc testing.
      Results: Response rates were 65%, 70%, 57%, and 47% for residents, pediatricians,
      RTs, and RNs, respectively. Themes were categorized into three priority groupings
      based on mean importance ratings. Where significant differences existed between
      residents and other respondent groups, pediatric residents rated the theme as
      being more important. Conclusion: This study provides an interprofessional
      assessment of pediatric residents' perceived ethics learning needs. High priority
      ethics topics were identified, allowing for targeted teaching. Pediatricians and
      allied HCPs did not rate any ethics themes higher than residents. Medical
      educators may consider using methods inspired by multisource feedback for program
      evaluation.

PMID- 29354203
TI  - Commentary: The physician as person framework: How human nature impacts empathy,
      depression, burnout, and the practice of medicine.

PMID- 29354202
TI  - The physician as person framework: How human nature impacts empathy, depression,
      burnout, and the practice of medicine.
AB  - Troubling trends of depression, burnout, and declines in empathy have been
      demonstrated amongst residents. I argue that while interventions in medical
      education are helpful, a new perspective on the issue requires a more fundamental
      understanding of this problem. Rather than training physicians to act in certain
      ways, we must first recognize that physicians are first and foremost people. This
      core principle forms the basis of the framework that educators can use to help
      learners. Five areas of humanity with implications for physicians are discussed:
      1) Physicians and patients share their humanity; 2) People are self-integrated in
      both personal and professional lives; 3) People are dynamic, thoughtful, and
      emotional; 4) People are finite; and 5) People are moral beings. Recognizing
      these can mitigate various factors contributing to current struggles. I also
      discuss practical implications of this framework to help residents flourish.

PMID- 29354204
TI  - Finding our way home.

PMID- 29354205
TI  - Trans-migrations: border-crossing and the politics of body modification among
      Puerto Rican transgender women.

PMID- 29354206
TI  - J Curve in Hypertension.
AB  - The relationship between blood pressure and cardiovascular disease risk among
      treated hypertensives is J-shaped: risk is increased at high levels of blood
      pressure, falls in parallel with blood pressure reduction and increases again
      when blood pressure falls below a nadir (the point at which blood pressure is too
      low to maintain perfusion of vital organs). Randomized controlled trials of
      antihypertensive treatment have identified J-shaped relationships between
      achieved systolic and diastolic blood pressures and all-cause mortality, as well
      as fatal and nonfatal cardiovascular events, but not stroke or renal outcomes, in
      the general population of hypertensives and high-risk prehypertensives,
      particularly in subgroups such as the elderly and those with coronary artery
      disease, chronic kidney disease, diabetes, left ventricular hypertrophy, and high
      cardiovascular risk because of multiple comorbidities and concomitant risk
      factors. Blood pressure targets <130-140/70-85 mm Hg were not beneficial for any
      outcome except stroke and chronic kidney disease.

PMID- 29354207
TI  - Dynamic contrast-enhanced magnetic resonance imaging of prostate cancer: A review
      of current methods and applications.
AB  - In many areas of oncology, dynamic contrast-enhanced magnetic resonance imaging
      (DCE-MRI) has proven to be a clinically useful, non-invasive functional imaging
      technique to quantify tumor vasculature and tumor perfusion characteristics.
      Tumor angiogenesis is an essential process for tumor growth, proliferation, and
      metastasis. Malignant lesions demonstrate rapid extravasation of contrast from
      the intravascular space to the capillary bed due to leaky capillaries associated
      with tumor neovascularity. DCE-MRI has the potential to provide information
      regarding blood flow, areas of hypoperfusion, and variations in endothelial
      permeability and microvessel density to aid treatment selection, enable frequent
      monitoring during treatment and assess response to targeted therapy following
      treatment. This review will discuss the current status of DCE-MRI in cancer
      imaging, with a focus on its use in imaging prostate malignancies as well as
      weaknesses that limit its widespread clinical use. The latest techniques for
      quantification of DCE-MRI parameters will be reviewed and compared.

PMID- 29354208
TI  - Endovascular treatment of pulmonary embolism: Selective review of available
      techniques.
AB  - Acute pulmonary embolism (PE) is the third most common cause of death in
      hospitalized patients. The development of sophisticated diagnostic and
      therapeutic modalities for PE, including endovascular therapy, affords a certain
      level of complexity to the treatment of patients with this important clinical
      entity. Furthermore, the lack of level I evidence for the safety and
      effectiveness of catheter directed therapy brings controversy to a promising
      treatment approach. In this review paper, we discuss the pathophysiology and
      clinical presentation of PE, review the medical and surgical treatment of the
      condition, and describe in detail the tools that are available for the
      endovascular therapy of PE, including mechanical thrombectomy, suction
      thrombectomy, and fibrinolytic therapy. We also review the literature available
      to date on these methods, and describe the function of the Pulmonary Embolism
      Response Team.

PMID- 29354209
TI  - Imaging features of intrathoracic complications of lung transplantation: What the
      radiologists need to know.
AB  - Lung transplantation has been a method for treating end stage lung disease for
      decades. Despite improvements in the preoperative assessment of recipients and
      donors as well as improved surgical techniques, lung transplant recipients are
      still at a high risk of developing post-operative complications which tend to
      impact negatively the patients' outcome if not recognised early. The recognised
      complications post lung transplantation can be broadly categorised into acute and
      chronic complications. Recognising the radiological features of these
      complications has a significant positive impact on patients' survival post
      transplantation. This manuscript provides a comprehensive review of the
      radiological features of post lung transplantations complications over a time
      continuum.

PMID- 29354211
TI  - Case of victims of modern imaging technology: Increased information noise
      concealing the diagnosis.
AB  - We present a case of tubercular arthritis who underwent numerous unnecessary
      investigations what is known as "victims of modern imaging technology" or VOMIT.
      Today there is an exponential rise in the volume of the medical imaging, part of
      which is contributed by unnecessary and unjustified indications. We discuss about
      the untoward effects of the uninhibited and careless use of modern imaging
      modalities and possible ways to avoid. Skeletal manifestation of the tuberculosis
      is still common in the endemic countries like India. Although the final diagnosis
      of the skeletal tuberculosis like tubercular arthritis is made by bacteriological
      and histological studies, few demographic, clinical and radiological features
      might help making early diagnosis.

PMID- 29354210
TI  - Aggressive blood pressure treatment of hypertensive intracerebral hemorrhage may
      lead to global cerebral hypoperfusion: Case report and imaging perspective.
AB  - Hypoperfusion injury related to blood pressure decrease in acute hypertensive
      intracerebral hemorrhage continues to be a controversial topic. Aggressive
      treatment is provided with the intent to stop the ongoing bleeding. However,
      there may be additional factors, including autoregulation and increased
      intracranial pressure, that may limit this approach. We present here a case of
      acute hypertensive intracerebral hemorrhage, in which aggressive blood pressure
      management to levels within the normal range led to global cerebral ischemia
      within multiple border zones. Global cerebral ischemia may be of concern in the
      management of hypertensive hemorrhage in the presence of premorbid poorly
      controlled blood pressure and increased intracranial pressure.

PMID- 29354212
TI  - Vascular cognitive impairment.

PMID- 29354213
TI  - Neuroimaging in cerebral small vessel disease: Update and new concepts.
AB  - In recent years, small vessel disease (SVD) has been recognized for its major
      impact on cognitive impairment in elderly people, where it is often difficult to
      separate its effects from those of neurodegenerative diseases individually. SVD
      is a systemic disease, probably related to diffuse endothelial dysfunction, which
      affects the perforating arterioles, capillaries and venules in the brain.
      Although often asymptomatic, it is responsible for almost half of all dementia
      cases and a significant proportion of stroke cases. Imaging features found on
      magnetic resonance include recent small subcortical infarctions, lacunes of
      presumed vascular origin, white matter hyperintensity of presumed vascular
      origin, prominent perivascular spaces and cerebral microbleeds. The recognition
      of these imaging findings as a spectrum of the same disease caused by endothelial
      dysfunction of small cerebral vessels can allow an overall analysis of the
      disease and thus the development of more effective preventive and therapeutic
      strategies.

PMID- 29354214
TI  - A panel of clinical and neuropathological features of cerebrovascular disease
      through the novel neuroimaging methods.
AB  - : The last decade has witnessed substantial progress in acquiring diagnostic
      biomarkers for the diagnostic workup of cerebrovascular disease (CVD). Advanced
      neuroimaging methods not only provide a strategic contribution for the
      differential diagnosis of vascular dementia (VaD) and vascular cognitive
      impairment (VCI), but also help elucidate the pathophysiological mechanisms
      ultimately leading to small vessel disease (SVD) throughout its course.
      Objective: In this review, the novel imaging methods, both structural and
      metabolic, were summarized and their impact on the diagnostic workup of age
      related CVD was analysed. Methods: An electronic search between January 2010 and
      2017 was carried out on PubMed/MEDLINE, Institute for Scientific Information Web
      of Knowledge and EMBASE. Results: The use of full functional multimodality in
      simultaneous Magnetic Resonance (MR)/Positron emission tomography (PET) may
      potentially improve the clinical characterization of VCI-VaD; for structural
      imaging, MRI at 3.0 T enables higher-resolution scanning with greater imaging
      matrices, thinner slices and more detail on the anatomical structure of vascular
      lesions. Conclusion: Although the importance of most of these techniques in the
      clinical setting has yet to be recognized, there is great expectancy in achieving
      earlier and more refined therapeutic interventions for the effective management
      of VCI-VaD.

PMID- 29354215
TI  - The role of biopsies and autopsies in the diagnosis of cognitive impairment, with
      emphasis on small vessel diseases: A critical appraisal enriched by personal
      experience.
AB  - Acquired and hereditary microangiopathies cause cerebral small vessel diseases
      (CSVD) that impair cognition. The most frequent is primary angiitis of the CNS
      (PACNS), whose diagnosis remains challenging, requiring a multidisciplinary
      approach. Secondary vasculitis, CADASIL, miscellaneous microangiopathies and
      lymphomas, also cause cognitive impairment. Despite the fact that the need for
      biopsy has decreased in the era of new neuroimaging methods, biopsies that
      include small leptomeningeal and parenchymal arterial vessels still remain the
      gold standard to diagnose PACNS and other CSVD, and to exclude mimics such as
      infections and malignancies. New approaches for pathological consequences
      relevant to vascular cognitive impairment such as silent brain lesions,
      microinfarcts, microbleeds and subtle loss of microstructural integrity, may be
      detected in autopsies. This article addresses the role of biopsies and autopsies
      for the diagnosis of cognitive impairment related to small vessel diseases or
      other inflammatory/ischemic processes, and presents a critical appraisal based on
      personal experience.

PMID- 29354217
TI  - A continuum of executive function deficits in early subcortical vascular
      cognitive impairment: A systematic review and meta-analysis.
AB  - Background: Subcortical Vascular Cognitive Impairment (SVCI) is a clinical
      continuum of vascular-related cognitive impairment, including Vascular Mild
      Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive
      Function (EF) are hallmarks of the disorder, but the best methods to assess this
      function have yet to be determined. The insidious and almost predictable course
      of SVCI and the multidimensional concept of EF suggest that a temporal
      dissociation of impairments in EF domains exists early in the disorder.
      Objective: This study aims to review and analyze data from the literature about
      performance of VaMCI patients on the most used EF tests through a meta-analytic
      approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using
      the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment
      no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR
      "executive function". Meta-analyses were conducted for each of the selected
      tests, using random-effect models. Results: Systematic review showed major
      discrepancies among the results of the studies included. Meta-analyses evidenced
      poorer performance on the Trail-Making Test part B and the Stroop color test by
      VaMCI patients compared to controls. Conclusion: A continuum of EF impairments
      has been proposed in SVCI. Early deficits appear to occur in cognitive
      flexibility and inhibitory control.

PMID- 29354216
TI  - Mixed dementia: A review of the evidence.
AB  - Mixed dementia is the coexistence of Alzheimer's disease and cerebrovascular
      disease (CVD) in the same demented patient. Currently, its diagnosis and
      treatment remains a challenge for practitioners. To provide an overview of the
      epidemiology, pathogenesis, natural history, diagnosis, and therapy of Mixed
      Vascular-Alzheimer Dementia (MVAD). The literature was reviewed for articles
      published between 1990-2016 by using the keywords linked to MVAD.
      Neuropathological studies indicate that MVAD is a very common pathological
      finding in the elderly with a prevalence about of 22%. The distinction between
      Alzheimer's dementia and vascular dementia (VD) is complex because their clinical
      presentation can overlap. There are international criteria for the MVAD
      diagnosis. The pharmacologic therapy shows modest clinical benefits that are
      similar among all drugs used in patients with Alzheimer's dementia and VD. The
      non-pharmacologic therapy includes the rigorous management of cardiovascular risk
      factors (especially hypertension) and the promotion of a healthy diet. The
      diagnosis and treatment of MVAD cannot be improved without further studies.
      Currently available medications provide only modest clinical benefits once a
      patient has developed MVAD. In subjects at risk, the antihypertensive therapy and
      healthy diet should be recommend for preventing or slowing the progression of
      MVAD.

PMID- 29354218
TI  - Evolution of short cognitive test performance in stroke patients with vascular
      cognitive impairment and vascular dementia: Baseline evaluation and follow-up.
AB  - : There is limited evidence about the progression of cognitive performance during
      the post-stroke stage. Objective: To assess the evolution of cognitive
      performance in stroke patients without vascular cognitive impairment (VCI),
      patients with vascular mild cognitive impairment (MCI), and patients with
      vascular dementia (VD). Methods: A prospective cohort of stroke outpatients from
      two secondary medical centers in Lima, Peru was studied. We performed
      standardized evaluations at definitive diagnosis (baseline evaluation), and
      control follow-ups at 6 and 12 months, including a battery of short cognitive
      tests: Clinical Dementia Rating (CDR), Addenbrooke's Cognitive Examination (ACE),
      and INECO Frontal Screening (IFS). Results: 152 outpatients completed the follow
      up, showing progressive increase in mean score on the CDR(0.34 to 0.46), contrary
      to the pattern observed on the ACE and IFS (78.18 to 76.48 and 23.63 to 22.24).
      The box plot for the CDR test showed that VCI patients had progressive worsening
      (0.79 to 0.16). Conversely, this trend was not observed in subjects without VCI.
      The box plot for the ACE and IFS showed that, for the majority of the
      differentiated stroke types, both non-VCI and VCI patients had progressive
      worsening. Conclusion: According to both ACE and IFS results during a 1-year
      follow-up, the cognitive performance of stroke patients worsened, a trend which
      was particularly consistent in infarction-type stroke patients.

PMID- 29354219
TI  - Impact of hypertension severity on arterial stiffness, cerebral vasoreactivity,
      and cognitive performance.
AB  - : Aging, hypertension (HTN), and other cardiovascular risk factors contribute to
      structural and functional changes of the arterial wall. Objective: To evaluate
      whether arterial stiffness (AS) is related to cerebral blood flow changes and its
      association with cognitive function in patients with hypertension. Methods: 211
      patients (69 normotensive and 142 hypertensive) were included. Patients with
      hypertension were divided into 2 stages: HTN stage-1 and HTN stage-2. The mini
      mental state examination (MMSE), Montreal Cognitive Assessment (MoCA) and a
      battery of neuropsychological (NPE) tests were used to determine cognitive
      function. Pulse wave velocity was measured using the Complior(r). Carotid
      properties were assessed by radiofrequency ultrasound. Central arterial pressure
      and augmentation index were obtained using applanation tonometry. Middle cerebral
      artery flow velocity was measured by transcranial Doppler ultrasonography.
      Results: Both arterial stiffness parameters and cerebral vasoreactivity worsened
      in line with HTN severity. There was a negative correlation between breath
      holding index (BHI) and arterial stiffness parameters. Cognitive performance
      worsened in line with HTN severity, with statistical difference occurring mainly
      between the HTN-2 and normotension groups on both the MMSE and MoCA. The same
      tendency was observed on the NPE tests. Conclusion: Hypertension severity was
      associated with higher AS, worse BHI, and lower cognitive performance.

PMID- 29354220
TI  - Hypertension, diabetes and obesity are associated with lower cognitive
      performance in community-dwelling elderly: Data from the FIBRA study.
AB  - Background: Systemic hypertension (SH), diabetes mellitus (DM) and abdominal
      obesity may negatively impact cognitive performance. Objective: To evaluate the
      association between SH, DM and abdominal obesity and cognitive performance among
      cognitively unimpaired elderly. Methods: A cross-sectional study of individuals
      aged 65+ from seven Brazilian cities was conducted. SH and DM diagnoses were self
      reported and abdominal circumference was objectively measured. Individuals who
      scored below the education-adjusted cutoff scores on the Mini-Mental State
      Examination (MMSE) were excluded. Results: Among 2,593 elderly, 321 (12.38%) had
      SH, DM and abdominal obesity concomitantly (Group I) and 421 (16.23%) had none of
      the three diseases (Group II). Group I had a higher proportion of individuals
      that were women, aged 70-74 years, illiterate and with lower income. Group I had
      a higher number of participants with low cognitive performance (28.04% vs. 17.58%
      in Group II). Variables associated with poor cognitive performance were: female
      gender (OR: 2.43, p < 0.001); and lower education (OR: 0.410, p < 0.001). The
      presence of the three diseases and age were not significant in the education
      adjusted model. Conclusion: There was an association between cognition and the
      presence of SH, DM and obesity. However, education seems to be decisive in
      determining cognitive performance in the presence of these three conditions.

PMID- 29354221
TI  - Association between diabetes and causes of dementia: Evidence from a
      clinicopathological study.
AB  - Background: Diabetes mellitus is a risk factor for dementia, especially for
      vascular dementia (VaD), but there is no consensus on diabetes as a risk factor
      for Alzheimer's disease (AD) and other causes of dementia. Objective: To explore
      the association between diabetes and the neuropathological etiology of dementia
      in a large autopsy study. Methods: Data were collected from the participants of
      the Brain Bank of the Brazilian Aging Brain Study Group between 2004 and 2015.
      Diagnosis of diabetes was reported by the deceased's next-of-kin. Clinical
      dementia was established when CDR >= 1 and IQCODE > 3.41. Dementia etiology was
      determined by neuropathological examination using immunohistochemistry. The
      association of diabetes with odds of dementia was investigated using multivariate
      logistic regression. Results: We included 1,037 subjects and diabetes was present
      in 279 participants (27%). The prevalence of dementia diagnosis was similar in
      diabetics (29%) and non-diabetics (27%). We found no association between diabetes
      and dementia (OR = 1.22; 95%CI = 0.81-1.82; p = 0.34) on the multivariate
      analysis. AD was the main cause of dementia in both groups, while VaD was the
      second-most-frequent cause in diabetics. Other mixed dementia was the second-most
      common cause of dementia and more frequent among non-diabetics (p = 0.03).
      Conclusion: Diabetes was not associated with dementia in this large
      clinicopathological study.

PMID- 29354222
TI  - Verbal fluency in elderly with and without hypertension and diabetes from the
      FIBRA study in Ermelino Matarazzo.
AB  - Background: There are few studies on the qualitative variables derived from the
      animal category verbal fluency test (VF), especially with data originating from
      low-income samples of community-based studies. Objective: To compare elderly with
      and without hypertension (HTN) and diabetes mellitus (DM) regarding the total
      number of animals spoken, number of categories, groups and category switches on
      the VF test. Methods: We used the database of the FIBRA (Frailty in Brazilian
      Elderly) community-based study. The variables number of Categories, Groups and
      Category Switches were created for each participant. The total sample (n = 384)
      was divided into groups of elderly who reported having HTN, DM, both HTN and DM,
      or neither of these conditions. Results: There were no significant differences
      between the groups with and without these chronic diseases for VF total score or
      for the qualitative variables. Conclusion: Among independent community-dwelling
      elderly, the qualitative variables derived from the VF animal category may not
      add information regarding the cognitive profile of elderly with chronic diseases.
      Total VF score and the qualitative variables Category, Group and Switching did
      not differentiate elderly with and without HTN and DM.

PMID- 29354223
TI  - Increased CSF levels of total Tau in patients with subcortical cerebrovascular
      pathology and cognitive impairment.
AB  - : Cognitive impairment includes mild cognitive decline and dementia, such as
      Alzheimer's disease (AD) and cerebrovascular-related pathologies. Objective: To
      investigate the profile of AD-related CSF biomarkers in a sample of cognitively
      impaired and unimpaired older adults with concomitant subcortical cerebrovascular
      burden. Methods: Seventy-eight older adults attending an outpatient
      psychogeriatric clinic were enrolled. Diagnoses were based on clinical,
      neuropsychological, laboratory, and neuroimaging data. Participants were
      classified into: cognitively normal (controls, n = 30), mild cognitive impairment
      (MCI, n = 34), and dementia (AD, n = 14). All subjects were submitted to CSF
      analyses for determination of amyloid-beta (Abeta1-42), total tau (t-tau),
      phosphorylated tau (p-tau) and Abeta1-42/p-tau ratio according to the Luminex
      method. MRI was performed in all individuals, and was scored independently by two
      experts according to Fazekas scale. Statistical analyses were conducted with the
      aid of general linear model procedures, and the Chi-squared test. Results: T-tau
      levels were significantly associated with subcortical lesion pattern when Fazekas
      was considered as a group factor. CSF biomarkers were not associated with MCI,
      AD, or controls when considered separately. There was a tendency for reduction in
      CSF Abeta1-42 together with increasing Fazekas scores, but without statistical
      significance. Comparisons of Abeta1-42 and t-tau with each clinical group or with
      each neuroimaging pattern did not reach statistical differences. Likewise,
      Fazekas scores had no impact on CAMCOG scores. Conclusion: We found a significant
      association between t-tau levels and subcortical lesions when all Fazekas
      classifications were considered as a single group; comparisons of Fazekas
      subgroups and CSF biomarkers did not reach significance.

PMID- 29354224
TI  - Cognitive performance in patients with Mild Cognitive Impairment and Alzheimer's
      disease with white matter hyperintensities: An exploratory analysis.
AB  - Background: White matter hyperintensities (WMH) are commonly associated with
      vascular dementia and poor executive functioning. Notwithstanding, recent
      findings have associated WMH with Alzheimer's disease as well as other cognitive
      functions, but there is no consensus. Objective: This study aimed to verify the
      relationship between WMH and cognitive performance in Mild Cognitive Impairment
      (MCI) and Alzheimer's disease (AD) patients. The study also sought to identify
      cognitive and demographic/cultural factors that might explain variability of WMH.
      Methods: The sample was composed of 40 participants (18 MCI and 22 AD patients)
      aged >= 65 years. Spearman's correlation was performed among cognitive
      performance (memory, language, visuospatial ability, and executive function) and
      WMH evaluated by the Fazekas and ARWMC scales. Two stepwise linear regressions
      were carried out, one with cognitive and the other with demographic/cultural
      variables as predictors. Results: Only naming showed significant correlation with
      ARWMC. Fazekas score exhibited significant correlation with all cognitive domains
      evaluated. Fazekas score was better predicted by episodic visual memory and age.
      Conclusion: This study found that the most relevant cognitive profile in MCI and
      AD patients with WMH was related to episodic memory. And, without taking clinical
      aspects into consideration, age was the best predictor of WMH.

PMID- 29354225
TI  - Efficacy of cognitive stimulation therapy for older adults with vascular
      dementia.
AB  - Background: Cognitive stimulation therapy (CST) is an evidence-based psychosocial
      intervention for people with mild-to-moderate dementia due to various etiological
      factors. Objective: The aim of the present study was to assess the efficacy of
      the CST program, Italian adaptation -CST-IT-, in individuals who have vascular
      dementia (VaD). Methods: Older adults with mild-to-moderate VaD (N = 35) were
      assigned to one of two programs: one group (N = 21) attended the 14 sessions of
      the CST-IT program, while the other, active control group (N = 14) took part in
      alternative activities. The following domains were examined: cognitive
      functioning, quality of life, mood, behavior, functional activities of daily
      living. Results: Compared with the active controls, the CST-IT group showed a
      greater improvement in general cognitive functioning after the intervention (i.e.
      score increase on the Mini-Mental State Examination and decrease on the
      Alzheimer's Disease Assessment Scale - Cognitive subscale). A trend towards
      improvement was also identified in short-term/working memory - the backward digit
      span task- and perceived quality of life (Quality of Life - Alzheimer's Disease
      scale). No significant differences emerged between the two groups for the other
      domains considered. Conclusion: The present results support the efficacy of CST
      in people with vascular dementia.

PMID- 29354226
TI  - Cardiovascular risk factors and cognitive performance in aging.
AB  - Background: Atherosclerosis in cerebral blood vessels, especially those which
      compose the Circle of Willis, can lead to reduced supply of oxygen and nutrients
      to different cortical structures, affecting cognitive function. Objective: To
      analyze whether cardiovascular risk factors negatively influence cognitive
      performance in adults and elderly. Methods: One hundred twenty-nine participants
      of both sexes, aged over 50 years, without cognitive or functional impairment
      were included. Body mass index (BMI), hypertension (HTN), diabetes mellitus (DM),
      smoking history, plasma levels of total cholesterol, low density lipoproteins
      (LDL), high density lipoproteins (HDL) and very low density lipoproteins (VLDL)
      cholesterol, triglycerides, and glucose were the cardiovascular risk factors
      analyzed. Cognitive assessment was performed using tests of attention, working
      memory, category fluency and declarative memory. Results: Controlling for age and
      education, multivariate linear regression models revealed that higher
      concentrations of triglycerides, as well as total, LDL and VLDL cholesterol, were
      associated with poorer performance on the digit span and category fluency tests.
      Higher HDL concentrations were associated with higher scores on category fluency
      tasks. Furthermore, higher BMI was associated with poorer delayed recall
      performance. Conclusion: The findings revealed that cardiovascular risk factors
      may negatively impact cognitive performance in aging.

PMID- 29354227
TI  - Apoplexy, cerebrovascular disease, and stroke: Historical evolution of terms and
      definitions.
AB  - The long-standing concept of "apoplexy' can be followed from Antiquity, passing
      through the Middle Ages and Renaissance, and reaching the Modern era and the
      present day, with the new designation of "stroke". The definition of "apoplexy"
      can be divided, by the history of autopsy, into a period predating this practice,
      which spanned from Antiquity until the Renaissance, with a relatively stable
      clinically-based umbrella concept, and an autopsy period of the Modern era, when
      the condition was subdivided into several subtypes. Thus, it took about 2,500
      years assembling the numerous pieces of information to achieve a fairly well
      defined picture. The "stroke" concept inherited the information developed for
      "apoplexy", incorporating all historical acquisitions to form the current state
      of this knowledge.

PMID- 29354228
TI  - Severe episodic memory impairment after strategic infarct: A case report.
AB  - Brain infarcts located in strategic regions often result in cognitive impairment.
      Based on a case study, this paper describes unusual and specific clinical and
      neuropsychological features of a strategic ischemic lesion in the left medial
      temporal lobe (MTL) structures. Taken together with the literature data, the case
      illustrates that a unilateral strategic infarct in MTL structures may result in
      severe impairment of episodic memory (EM), which refers to the ability to encode
      and retrieve personal experiences, including information about the time and place
      of an event and detailed description of the event itself. The preservation of
      other cognitive functions, the severe functional impairment, and the type of
      visual-verbal deficit in a left-sided lesion were identified as singular features
      of the case. The current case supports the critical role of the MTL structures in
      EM formation.

PMID- 29354229
TI  - Gerstmann's syndrome and unilateral optic ataxia in the emergency department.
AB  - A 75-year-old right-handed woman presented to the emergency department with
      simultanagnosia and right unilateral optic ataxia. Moreover, the patient had
      agraphia, acalculia, digital agnosia and right-left disorientation, consistent
      with complete Gerstmann's syndrome. This case highlights the concurrence of
      Gerstmann's syndrome and unilateral optic ataxia in the acute phase of a left
      middle cerebral artery stroke.

PMID- 29354230
TI  - Posttraumatic Delayed Vertebral Collapse : Kummell's Disease.
AB  - Posttraumatic delayed vertebral collapse, known as Kummell's disease, is
      increasing in number of patients. This disease is already progressive kyphosis
      due to vertebral collapse at the time of diagnosis and it causes intractable pain
      or neurologic deficit due to intravertebral instability. Treatment is very
      difficult after progression of the disease, and the range of treatment, in
      hospital day, and cost of treatment are both increased. Clinical features,
      pathogenesis and radiologic findings of these disease groups were reviewed to
      determine risk factors for delayed vertebral collapse. The purpose of this
      article is to suggest appropriate treatment before vertebral collapse for
      patients with osteoporotic vertebral compression fracture who have risk factors
      for posttraumatic delayed vertebral collapse.

PMID- 29354231
TI  - Curcumin Increase the Expression of Neural Stem/Progenitor Cells and Improves
      Functional Recovery after Spinal Cord Injury.
AB  - Objective: To investigates the effect of curcumin on proliferation of spinal cord
      neural stem/progenitor cells (SC-NSPCs) and functional outcome in a rat spinal
      cord injury (SCI) model. Methods: Sixty adult male Sprague-Dawley rats were
      randomly and blindly allocated into three groups (sham control group; curcumin
      treated group after SCI; vehicle treated group after SCI). Functional recovery
      was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale during 6 weeks
      after SCI. The expression of SC-NSPC proliferation and astrogliosis were analyzed
      by nestin/Bromodeoxyuridine (BrdU) and Glial fibrillary acidic protein (GFAP)
      staining. The injured spinal cord was then examined histologically, including
      quantification of cavitation. Results: The BBB score of the SCI-curcumin group
      was better than that of SCI-vehicle group up to 14 days (p<0.05). The co
      immunoreactivity of nestin/BrdU in the SCI-curcumin group was much higher than
      that of the SCI-vehicle group 1 week after surgery (p<0.05). The GFAP
      immunoreactivity of the SCI-curcumin group was remarkably lower than that of the
      SCI-vehicle group 4 weeks after surgery (p<0.05). The lesion cavity was
      significantly reduced in the curcumin group as compared to the control group
      (p<0.05). Conclusion: These results indicate that curcumin could increase the
      expression of SC-NSPCs, and reduce the activity of reactive astrogliosis and
      lesion cavity. Consequently curcumin could improve the functional recovery after
      SCI via SC-NSPC properties.

PMID- 29354232
TI  - Treatment Outcomes with Selective Coil Embolization for Large or Giant Aneurysms
      : Prognostic Implications of Incomplete Occlusion.
AB  - Objective: The objectives of this study were to evaluate the immediate and long
      term efficacy and safety of coil embolization for large or giant aneurysms.
      Methods: One hundred and fifty large or giant aneurysm cases treated with
      endovascular coil embolization between January 2005 and February 2014 at a single
      institute were included in this study. Medical records and imaging findings were
      reviewed. Statistical analysis was performed to evaluate prognostic factors
      associated with major recurrence (major recanalization or rupture) and delayed
      thromboembolism after selective coil embolization. Results: Procedure-related
      symptomatic complications occurred in five (3.3%) patients. The mean clinical and
      radiological follow-up periods were 38 months (range, 2-110) and 26 months
      (range, 6-108), respectively. During the follow-up period, the estimated
      recurrence rate was 4.6% per year. Multivariate analysis using Cox regression
      showed the degree of occlusion to be the only factor associated with recurrence
      (p=0.008, hazard ratio 3.15, 95% confidence interval 1.34-7.41). The patient's
      history of rupture in addition to the size and location of the aneurysm were not
      associated with recurrence in this study. Delayed infarction occurred in eight
      cases, and all were incompletely occluded. Conclusion: Although immediate
      postprocedural safety profiles were reasonable, longterm results showed
      recanalization and thromboembolic events to occur continuously, especially in
      patients with incomplete occlusion. In addition, incomplete occlusion was
      associated with delayed thromboembolic complications. Patients with incomplete
      occlusions should be followed carefully for delayed recurrence or delayed
      thromboembolic events.

PMID- 29354233
TI  - Duplicated Vertebral Artery : Literature Review and Clinical Significance.
AB  - Objective: Duplication of the vertebral artery (VA) is a rare vascular variant.
      This paper describes the anatomy and embryological development of duplicated VAs
      and reviews the clinical significance. Methods: Computed tomography (CT)
      angiography was performed in 3386 patients (1880 females, 1506 males) between
      March 2014 and November 2015. We defined duplication of the VA as a condition in
      which the VA has two origins that fused at different levels of the neck. Results:
      Ten of the 3386 patients (0.295%) who received CT angiography had a dual origin
      of the VA; three on the left side, and seven on the right side. In all seven with
      right dual origin of the VA, both limbs of the VA origin originated from the
      right subclavian artery. In all three patients with left dual origin of the VA,
      both limbs of the VA originated from the left subclavian artery and aortic arch.
      In all 10 patients, the medial limb of the duplicated VA was located posteriorly
      and medially to the common carotid artery (CCA) and anteriorly and laterally to
      the vertebral transverse foramen. In two patients, the medial limb of the
      duplicated VA was located in close proximity to the CCA. In another two patients,
      the medial limb of the duplicated VA was located in close proximity to the CCA,
      carotid bifurcation, and proximal internal carotid artery. Conclusion: Although
      duplication of the VA is asymptomatic in most patients, clinicians should
      consider this anomaly during diagnosis and treatment.

PMID- 29354234
TI  - Risk Factors of Rehemorrhage in Postoperative Patients with Spontaneous
      Intracerebral Hemorrhage : A Case-Control Study.
AB  - Objective: Rehemorrhage is the most severe complication of postoperative patients
      with spontaneous intracerebral hemorrhage. The aim of the present study was to
      assess independent predictors of rehemorrhage and find the possibility of
      preventing rehemorrhage in postoperative patients with spontaneous intracerebral
      hemorrhage (sICH). Methods: Medical records of 263 postoperative patients with
      sICH from our Hospital were reviewed. The relationships between rehemorrhage and
      parameters were examined by univariate and multivariate analyses. The parameters
      include time from onset to surgery, hematologic paremeters, neuroimaging
      characteristics, level and variability of systolic blood pressure, medical
      histories, operation duration, and blood loss. In addition, relationship between
      rehemorrhage and clinical outcome were analyzed by using multivariate analyses.
      Results: Thirty-five (13.31%) patients experienced rehemorrhage after operation.
      Multivariate analyses indicated that the following factors were independently
      associated with rehemorrhage : history of diabetes mellitus (odds ratio [OR],
      2.717; 95% confidence interval [CI], 1.005-7.346; p=0.049), and midline shift
      (for every 1 mm increase, OR, 1.117; 95% CI, 1.029-1.214; p=0.009). Rehemorrhage
      was an independent risk factor of poor functional outcome (OR, 3.334; 95% CI,
      1.094-10.155; p=0.034). Conclusion: Our finding revealed that history of diabetes
      mellitus and admission midline shift were possibly associated with rehemorrhage
      in postoperative patients with sICH.

PMID- 29354236
TI  - Gamma Knife Radiosurgery for Cancer Metastasized to the Ocular Choroid.
AB  - Objective: Choroidal metastases (CMs) are the most common intraocular tumor.
      Management is mainly radiation therapy with goals of pain control and visual
      improvement. However, many radiation-related complications are reported. Since
      gamma knife radiosurgery (GKS) for CM was first reported in 1995, few cases have
      been reported. We report 7 cases of CMs treated with GKS. Methods: From April
      2011 to November 2014, 7 patients with CM underwent GKS. Their median age at
      treatment was 64 years (range, 51-71 years). Four males and three females were
      treated. Lung cancer was the most common primary pathology, followed by renal
      cell carcinoma and stomach cancer. Four patients had multiple cerebral lesions
      and were treated simultaneously for choroidal lesions. The median marginal dose
      of 20 Gy (range, 15-25 Gy) was administered at the 50% isodose line. Results:
      Median follow-up period after GKS was 8 months (range, 2-38.3 months). Four
      patients expired due to underlying malignancy progression. Except for two
      patients who were not followed with magnetic resonance image after GKS, all
      patients showed size reduction in the treated lesions, but a new choroidal lesion
      appeared in one patient and one recurred. Six of seven patients reported
      subjectively improved visual symptoms. Visual acuity improved in 2 patients, and
      2 were stable upon objective examination. One patient showed no improvement in
      visual acuity, but ocular pain was relieved; another patient showed improved
      vision and tumor remission, but visual deterioration recurred. Conclusion: GKS
      was shown to be safe and effective and should be considered for CM treatment.

PMID- 29354235
TI  - Compare the Intracranial Pressure Trend after the Decompressive Craniectomy
      between Massive Intracerebral Hemorrhagic and Major Ischemic Stroke Patients.
AB  - Objective: Massive intracerebral hemorrhage (ICH) and major infarction (MI) are
      devastating cerebral vascular diseases. Decompression craniectomy (DC) is a
      common treatment approach for these diseases and acceptable clinical results have
      been reported. Author experienced the postoperative intracranaial pressure (ICP)
      trend is somewhat different between the ICH and MI patients. In this study, we
      compare the ICP trend following DC and evaluate the clinical significance.
      Methods: One hundred forty-three patients who underwent DC following massive ICH
      (81 cases) or MI (62 cases) were analyzed retrospectively. The mean age was
      56.3+/-14.3 (median=57, male : female=89 : 54). DC was applied using consistent
      criteria in both diseases patients; Glasgow coma scale (GCS) score less than 8
      and a midline shift more than 6 mm on brain computed tomography. In all patients,
      ventricular puncture was done before the DC and ICP trends were monitored during
      and after the surgery. Outcome comparisons included the ictus to operation time
      (OP-time), postoperative ICP trend, favorable outcomes and mortality. Results:
      Initial GCS (p=0.364) and initial ventricular ICP (p=0.783) were similar among
      the ICH and MI patients. The postoperative ICP of ICH patients were drop rapidly
      and maintained within physiological range if greater than 80% of the hematoma was
      removed. While in MI patients, the postoperative ICP were not drop rapidly and
      maintained above the physiologic range (MI=18.8 vs. ICH=13.6 mmHg, p=0.000). The
      OP-times were faster in ICH patients (ICH=7.3 vs. MI=40.9 hours, p=0.000) and the
      mortality rate was higher in MI patients (MI=37.1% vs. ICH=17.3%, p=0.007).
      Conclusion: The results of this study suggest that if greater than 80% of the
      hematoma was removed in ICH patients, the postoperative ICP rarely over the
      physiologic range. But in MI patients, the postoperative ICP was above the
      physiologic range for several days after the DC. Authors propose that DC is no
      need for the massive ICH patient if a significant portion of their hematoma is
      removed. But DC might be essential to improve the MI patients' outcome and timely
      treatment decision.

PMID- 29354237
TI  - Novel Genetic Variants Associated with Lumbar Spondylosis in Koreans : A Genome
      Wide Association Study.
AB  - Objective: The aim of this study was to identify the susceptibility genes
      responsible for lumbar spondylosis (LS) in Korean patients. Methods: Data from
      1427 subjects were made available for radiographic grading and genome wide
      association studies (GWAS) analysis. Lateral lumbar spine radiographs were
      obtained and the various degrees of degenerative change were semi-quantitatively
      scored. A pilot GWAS was performed using the AffymetrixGenome-Wide Human single
      nucleotide polymorphisms (SNPs), 500K array. A total of 352228 SNPs were analyzed
      and the association between the SNPs and case-control status was analyzed by
      stepwise logistic regression analyses. Results: The top 100 SNPs with a cutoff p
      value of less than 3.7*10-4 were selected for joint space narrowing, while a
      cutoff p-value of 6.0*10-4 was applied to osteophytes and the Kellgren-Lawrence
      (K-L) osteoarthritis grade. The SNPs with the strongest effect on disc space
      narrowing, osteophytes, and K-L grade were serine incorporator 1 (rs155467, odds
      ratio [OR]=17.58, p=1.6*10-4), stromal interaction molecule 2 (STIM1, rs210781,
      OR=5.53, p=5*10-4), and transient receptor potential cation channel, subfamily C
      (rs11224760, OR=3.99, p=4.8*10-4), respectively. Leucine-rich repeat-containing G
      protein-coupled receptor 4 was significantly associated with both disc space
      narrowing and osteophytes (rs1979400, OR=2.01, p=1.1*10-4 for disc space
      narrowing, OR=1.79, p=3*10-4 for osteophytes), while zinc finger and BTB domain
      containing 7C was significantly and negatively associated with both osteophytes
      and a K-L grade >2 (rs12457004,OR=0.25, p=5.8*10-4 and OR=0.27, p=5.3*10-4,
      respectively). Conclusion: We identified SNPs that potentially contribute to the
      pathogenesis of LS. This is the first report of a GWAS in an Asian population.

PMID- 29354238
TI  - Freehand S2 Alar-Iliac Screw Placement Using K-Wire and Cannulated Screw :
      Technical Case Series.
AB  - Objective: Among the various sacropelvic fixation methods, S2 alar-iliac (S2AI)
      screw fixation has several advantages compared to conventional iliac wing screw.
      However, the placement of S2AI screw still remains a challenge. The purpose of
      this study was to describe a novel technique of free hand S2AI screw insertion
      using a K-wire and cannulated screw, and to evaluate the accuracy of the
      technique. Methods: S2AI screw was inserted by free hand technique in sixteen
      consecutive patients without any fluoroscopic guidance. The gearshift was
      advanced to make a pilot hole passing through the sacroiliac joint and directing
      the anterior inferior iliac spine. A K-wire was placed through the pilot hole.
      After introducing a cannulated tapper along with the K-wire, a cannulated S2AI
      screw was installed over the K-wire. Results: Thirty-three S2AI screws were
      placed in sixteen consecutive patients. Thirty-two screws were cannulated screws,
      and one screw was a conventional non-cannulated screw. Thirty out of 32 (93.8%)
      cannulated screws were accurately positioned, whereas two cannulated screws and
      one non-cannulated screw violated lateral cortex of the ilium. Conclusion: The
      technique using K-wire and cannulated screw can provide accurate placement of
      free hand S2AI screw.

PMID- 29354240
TI  - Morphometric Study of the Lumbar Posterior Longitudinal Ligament.
AB  - Objective: Morphometric data for the lumbar posterior longitudinal ligament (PLL)
      was investigated to identify whether there is a difference in the morphometry of
      the PLL of the lumbar spine at each level with respect to the pattern of
      intervertebral disc displacement. Methods: In 14 formalin-fixed adult cadavers
      (12 males and 2 females), from L1 to L5, the authors measured the width and
      height of the PLL and compared them with other landmarks such as the disc and the
      pedicle. Results: Horizontally, at the upper margin of the disc, the central
      portion of the superficial PLL covered 17.8-36.9% of the disc width and the fan
      like portion of the PLL covered 63.9-76.7% of the disc width. At the level of the
      median portion of the disc, the PLL covered 69.1-74.5% of the disc width.
      Vertically, at the level of the medial margin of the pedicle, the fan-like
      portion of the PLL covered 23.5-29.9% of the disc height. In general, a
      significant difference in length was not found in the right-left and male-female
      comparisons. Conclusion: This study presents the morphometric data on the pattern
      of intervertebral disc displacement and helps to improve the knowledge of the
      surgical anatomy of the lumbar PLL.

PMID- 29354239
TI  - Comparative Analysis of Spontaneous Infectious Spondylitis : Pyogenic versus
      Tuberculous.
AB  - Objective: Spondylitis is often chemotherapy resistant and requires long-term
      treatment. Without adequate chemotherapy, the outcome can be fatal or result in
      severe neurologic damage. Therefore, differentiating the etiology of spondylitis
      is very important, particularly in spontaneous cases. As the prevalence of
      tuberculosis in Korea has decreased in recent years, updated clinical research
      about spondylitis is warranted. Methods: From April 2010 to March 2016, data from
      spondylitis patients were collected retrospectively. In total, 69 patients (51
      with pyogenic spondylitis and 18 with tuberculous spondylitis) were included.
      Clinical data, laboratory findings including erythrocyte sedimentation rate (ESR)
      and C-reactive protein (CRP) level, measurements of Cobb angles at the initial
      and final follow-up, and radiologic features on magnetic resonance imaging (MRI)
      scans were evaluated. To test differences between the pyogenic and tuberculous
      groups, numerical data were compared using the student's t-test and Mann-Whitney
      U test, and categorical data were compared using the chi-square test and Fisher's
      exact test. Results: The patients' mean age was 60.0 years. Male sex was slightly
      predominant (56.5%). There was no difference in mean age and sex between the two
      groups. The pyogenic group had a relatively higher proportion of
      immunocompromised patients. The peak CRP value was higher in the pyogenic group
      than in the tuberculous group (14.08 mg/dL and 8.50 mg/dL, respectively,
      p=0.009), whereas the ESR was not significantly different between the groups
      (81.5 mm/h and 75.6 mm/h, respectively, p=0.442). Radiologically, the presence of
      disc space sparing and vertebral body collapse differed between the groups. In
      the tuberculous group, the disc was more commonly preserved on contrast-enhanced
      MRI (50% and 23.5%, respectively, p=0.044), and vertebral body collapse was more
      common (66.6% and 15.7%, respectively, p<0.001). The mean length of
      hospitalization was longer in the pyogenic group (56.5 days and 41.2 days,
      respectively, p=0.001). Four mortality cases were observed only in the pyogenic
      group. The most commonly isolated microorganism in the pyogenic group was
      Staphylococcus aureus (S. aureus) (methicillin susceptible S. aureus and
      methicillin resistant S. aureus [MRSA] in 8 and 4 cases, respectively).
      Conclusion: The clinical and radiological manifestations of spontaneous
      spondylitis differ based on the causative organism. Pyogenic spondylitis patients
      tend to have a higher CRP level and a more severe clinical course, whereas
      tuberculous spondylitis patients present with destruction of the vertebral body
      with disc sparing more frequently. The presence of MRSA is increasing in
      community-acquired spondylitis cases.

PMID- 29354241
TI  - The Potential of Diffusion-Weighted Magnetic Resonance Imaging for Predicting the
      Outcomes of Chronic Subdural Hematomas.
AB  - Objective: Diffusion-weighted magnetic resonance imaging (DW-MRI) has proven
      useful in the study of the natural history of ischemic stroke. However, the
      potential of DW-MRI for the evaluation of chronic subdural hematoma (CSDH) has
      not been established. In this study, we investigated DW-MRI findings of CSDH and
      evaluated the impact of the image findings on postoperative outcomes of CSDH.
      Methods: We studied 131 CSDH patients who had undergone single burr hole drainage
      surgery. The images of the subdural hematomas on preoperative DW-MRI and computed
      tomography (CT) were divided into three groups based on their signal intensity
      and density: 1) homogeneous (iso or low) density on CT and homogeneous low signal
      intensity on DW-MRI; 2) homogeneous (iso or low) density on CT and mixed signal
      intensity on DW-MRI; and 3) heterogeneous density on CT and mixed signal
      intensity on DW-MRI. On the basis of postoperative CT, we also divided the
      patients into 3 groups of surgical outcomes according to residual hematoma and
      mass effect. Results: Analysis showed statistically significant differences in
      surgical (A to B: p<0.001, A to C: p<0.001, B to C: p=0.129) and functional (A to
      B: p=0.039, A to C: p<0.001, B to C: p=0.108) outcomes and treatment failure
      rates (A to B: p=0.037, A to C: p=0.03, B to C: p=1) between the study groups. In
      particular, group B and group C showed worse outcomes and higher treatment
      failure rates than group A. Conclusion: CSDH with homogeneous density on CT was
      characterized by signal intensity on DW-MRI. In CSDH patients, performing DW-MRI
      as well as CT helps to predict postoperative treatment failure or complications.

PMID- 29354242
TI  - Geographic Analysis of Neurosurgery Workforce in Korea.
AB  - Objective: In respect of the health and safety of the public, universal access to
      health care is an issue of the greatest importance. The geographic distribution
      of doctors is one of the important factors contributing to access to health care.
      The aim of this study is to assess the imbalances in the geographic distribution
      of neurosurgeons across Korea. Methods: Population data was obtained from the
      National Statistical Office. We classified geographic groups into 7 metropolitan
      cities, 78 non-metropolitan cities, and 77 rural areas. The number of doctors and
      neurosurgeons per 100000 populations in each county unit was calculated using the
      total number of doctors and neurosurgeons at the country level from 2009 to 2015.
      The density levels of neurosurgeon and doctor were calculated and depicted in
      maps. Results: Between 2009 and 2015, the number of neurosurgeons increased from
      2002 to 2557, and the ratio of neurosurgeons per 100000 populations increased
      from 4.02 to 4.96. The number of neurosurgeons per 100000 populations was highest
      in metropolitan cities and lowest in rural areas from 2009 to 2015. A comparison
      of the geographic distribution of neurosurgeons in 2009 and 2015 showed an
      increase in the regional gap. The neurosurgeon density was affected by country
      unit characteristics (p=0.000). Conclusion: Distribution of neurosurgeons
      throughout Korea is uneven. Neurosurgeons are being increasingly concentrated in
      a limited number of metropolitan cities. This phenomenon will need to be
      accounted when planning for a supply of neurosurgeons, allocation of resources
      and manpower, and the provision of regional neurosurgical services.

PMID- 29354243
TI  - Posterior Screw Fixation in Previously Augmented Vertebrae with Bone Cement: Is
      It Inapplicable?
AB  - Objective: The purpose of this study was to determine the feasibility of screw
      fixation in previously augmented vertebrae with bone cement. We also investigated
      the influence of cement distribution pattern on the surgical technique. Methods:
      Fourteen patients who required screw fixation at the level of the previous
      percutaneous vertebroplasty or balloon kyphoplasty were enrolled in this study.
      The indications for screw fixation in the previously augmented vertebrae with
      bone cement included delayed complications, such as cement dislodgement, cement
      leakage with neurologic deficits, and various degenerative spinal diseases, such
      as spondylolisthesis or foraminal stenosis. Clinical outcomes, including pain
      scale scores, cement distribution pattern, and procedure-related complications
      were assessed. Results: Three patients underwent posterior screw fixation in
      previously cemented vertebrae due to cement dislodgement or progressive kyphosis.
      Three patients required posterior screw fixation for cement leakage or
      displacement of fracture fragments with neurologic deficits. Eight patients
      underwent posterior screw fixation due to various degenerative spinal diseases.
      It was possible to insert screws in the previously augmented vertebrae regardless
      of the cement distribution pattern; however, screw insertion was more difficult
      and changed directions in the patients with cemented vertebrae exhibiting a solid
      pattern rather than a trabecular pattern. All patients showed significant
      improvements in pain compared with the preoperative levels, and no patient
      experienced neurologic deterioration as seen at the final follow-up. Conclusion:
      For patients with vertebrae previously augmented with bone cement, posterior
      screw fixation is not a contraindication, but is a feasible option.

PMID- 29354244
TI  - Intraparenchymal Atypical Meningioma in Basal Ganglia Region in a Child: Case
      Report and Literature Review.
AB  - Intraparenchymal meningiomas without dural attachment are extremely rare,
      especially when they occur in basal ganglia region in child. An 8-year-old boy
      was admitted at our hospital, complaining of recurrent headache and vomiting for
      3 months. Neurological examination showed impaired vision and mild paresis of the
      left extremities. Magnetic resonance imaging demonstrated a lesion located in the
      right basal ganglia region extending to superasellar cistern with solid, multiple
      cystic and necrotic components. Computed tomography revealed calcification within
      the mass. Due to the anterior cerebral artery involvement, a subtotal resection
      was achieved and postoperative radiotherapy was recommended. Histopathological
      examination indicated that the lesion was an atypical meningioma. The
      postoperative rehabilitation was uneventful. Mildly impaired vision and motor
      weakness of left extremities improved significantly and the patient returned to
      normal life after surgery. To our knowledge, intraparenchymal atypical meningioma
      in basal ganglia extending to superasellar cistern was never reported. The
      significance in differential diagnosis of lesions in basal ganglia should be
      emphasized.

PMID- 29354245
TI  - Effects of systemic administration of HESA-A on the expression of cyclin D1 and
      EGFR and E-cadherin in the induced tongue dysplasia in rats.
AB  - Background. HESA-A has herbal and marine bases, containing minerals and rare
      elements such as Zr, Cr, Ga, Mn, Mg, Ca, Sr, Cu, Ti, etc. Its mechanism of action
      includes antioxidant, antiinflammatory and adjustment of the immune system. The
      aim of this study was to evaluate the effects of HESA-A systemic drug on
      expression of cyclin D1, EGFR and E-cadherin in induced tongue dysplasia in rats.
      Methods. In this experimental study, the effects of the systemic drug HESA-A on
      the expression of cyclin D1, EGFR, and E-cadherin molecular markers were examined
      in induced tongue dysplasia in rats. Results. The incidence rate of cyclin D1 in
      groups receiving HESA-A was lower than the group that did not receive the drug
      (77.78% in the 0-5% range versus 77.78% in the 5-50% range). In the case of
      expression of E-cadherin in group D, which did not receive HESA-A, a decrease was
      observed in the expression of this cell adhesion marker as compared to the other
      two groups. The incidence of E-cadherin was dependent on HESA-A dose, while with
      500 mg/kg it was higher than other groups (>75% in 55.55% versus >75% in 11.11%).
      Concerning the incidence of EGFR in all the three groups most cases were grade 0.
      Conclusion. The results of the present research indicated that considering
      changes in the expression of cyclin D1 and E-cadherin markers in groups treated
      with HESA-A, HESA-A(r) has preventive effects on development of cancer in
      dysplastic lesions through regulation of expression of these molecules.

PMID- 29354246
TI  - The prophylactic effect of Acetobacter syzygii probiotic species against squamous
      cell carcinoma.
AB  - Background. Squamous cell carcinoma is a prevalent carcinoma of the oral cavity.
      Recently anti-proliferative effect of probiotics has been considered and assessed
      against different cancers. The aim of this study was to evaluate the cytotoxicity
      of Acetobacter syzygii strain supernatant on KB human oral cancer cell line and
      KDR human epithelial normal cell line. Methods. The cytotoxicity assessments were
      performed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      (MTT) as well as through qualitative (4',6-diamidino-2-phenylindole staining) and
      quantitative (flow cytometry assessments using the BD Biosciences Annexin V-FITC
      Kit) evaluations of apoptosis. Results.A. syzygii secretions exhibited
      significant cytotoxicity against KB cancer cell lines similar to cisplatin (75.7%
      apoptosis) while the rate of apoptosis in KDR normal cells was only 9.36%. The
      prophylactic effects of Lactobacillus acidophilus (PTCC 1643), as a reference
      bacterium, was similar to A. syzygii, indicating beneficial effects of useful
      bacteria on prevention of oral diseases. Conclusion. The anticancer bioactivity
      of A. syzygii strain secretions depends on the induction of apoptosis in KB
      cancer cells. However, several investigations should be conducted to precisely
      determine effective compounds to be used as anticancer therapeutics in the
      future.

PMID- 29354247
TI  - Antibacterial effect of different concentrations of sodium hypochlorite on
      Enterococcus faecalis biofilms in root canals.
AB  - Background. The aim of this study was to evaluate the effectiveness of different
      concentrations of sodium hypochlorite (NaOCl) solution in reducing bacterial
      growth in Enterococcus faecalis biofilms in root canals. Methods. The root canals
      of maxillary central incisors of 104 subjects underwent chemomechanical
      debridement. In order to remove the smear layer, 5.25% sodium hypochlorite
      solution was used for 3 minutes in the root canals. Then, the samples were
      immersed in 1 mL of 17% EDTA for 3 minutes. Finally, the root canals were
      irrigated with phosphate-buffered saline (PBS) solution. After removing the smear
      layer, the samples were sterilized. Then E. faecalis biofilms formed within the
      root canals at 4-, 6-, and 10-week intervals were evaluated. Each group was
      divided into 4 subgroups in terms of the antibacterial treatment: group 1: 1%
      NaOCl solution; group 2: 2.5% NaOCl solution; group 3: 5.25% NaOCl solution; and
      group 4: PBS solution. After preparation of root canal filings, the counts of
      live bacteria were calculated through the classic method of counting, i.e. colony
      forming units (CFU), followed by the analysis of data. Results. In groups 2 and
      3, there was no bacterial growth due to complete removal of E. faecalis biofilms
      (P<0001), while the bacterial counts in group 1 at 4-, 6- and 10-week intervals
      decreased compared to the control group. Conclusion. The bacterial cells in
      mature and old biofilms have higher resistance to 1% NaOCl solution compared to
      the young biofilms. However, the 2.5% and 5.25% NaOCl solutions caused complete
      inhibition of the growth of E. faecalis biofilm in all the stages of development.

PMID- 29354248
TI  - Effect of preheat repetition on color stability of methacrylate- and silorane
      based composite resins.
AB  - Background. The aim of this study was to investigate the effect of preheating
      methacrylate- and silorane-based composite resins on their color stability up to
      40 times at 55-60 degrees C. Methods. Seventy-six methacrylate and silorane-based
      composite resin samples, with a diameter of 10 mm and a height of 2 mm, were
      divided into 4 groups (n=19). After the samples were prepared, their color
      parameters were determined using a reflective spectrophotometer. The composite
      resin samples were separately stored in a solution of tea for 40 consecutive
      days. Then the samples underwent a color determination procedure again using a
      spectrophotometer and color changes were recorded. Finally two-way ANOVA was used
      to study the effect of composite temperature on its staining (P<0.05).
      Independent-samples t-test was used to evaluate changes in conversion rates of
      preheated composite resin samples compared to non-heated samples at P=0.005 and
      P=0.029 for silorane-based and Z250 composite resin samples, respectively.
      Results. Both composite resin type (P=0.014) and preheating (P<0.001) had
      significant effects on DeltaE. Conclusion. Repeated preheating of methacrylate-
      and silorane-based composite resin samples, up to 55-60 degrees C for 40 rounds,
      resulted in more color changes compared with unheated composite resin samples.
      After storage in a solution of tea the color change rate in the composite resin
      samples of silorane-based was higher than the Z250 composite resin samples.

PMID- 29354250
TI  - Effects of adjective use of melatonin and vitamin C in the treatment of chronic
      periodontitis: A randomized clinical trial.
AB  - Background. Melatonin can eliminate free radicals and this function can be
      intensified byvitamin C. Melatonin and vitamin C can have synergic antioxidant
      effects. The aim of thisstudy was to investigate the effects of adjunctive use of
      melatonin and vitamin C in the non-surgical treatment of chronic periodontitis.
      Methods. Sixty subjects with chronic periodontitis were included in this study
      and randomly allocated to three groups: group 1) 20 patients received non
      surgical periodontal treatment; group 2) 20 patients received non-surgical
      periodontal treatment with adjunctive use of melatonin; and group3) 20 patients
      received non-surgical periodontal treatment with combination use of melatonin +
      vitamin C. Clinical parameters (PD, CAL,GI) were recorded at baseline and at 3
      month and 6-month intervalsafter treatment. Data were analyzed with paired t
      test, one-way ANOVA andrepeated-measures ANOVA. A significant difference was
      assumed at P<0.05. Results. Non-surgical periodontal therapy improved PD and CAL
      3 and 6 months treatment compared to baseline (P<0.001). There was a significant
      improvement in PD and CAL scores at 6-month interval compared to 3 months in the
      melatonin+ vitamin C group (P<0.05), while the differences in PD and CAL scores
      between the mentioned intervals were not significant between the control and
      melatonin groups (P>0.05). Therefore adjunctive dose of vitamin C offered an
      additional effect at this interval. Conclusion. Combination therapy with
      melatonin and vitamin C can improve the results of non-surgical periodontal
      therapy.

PMID- 29354249
TI  - Clinical and histological evaluation of increase in the residual ridge width
      using mineralized corticocancellous block allografts: A pilot study.
AB  - Background. Lateral ridge augmentation is conventionally accomplished by means of
      autogenous bone grafts. However, due to its complications, the application of
      autogenous bone graft substitutes, e.g. mineralized corticocancellous allograft,
      is ecommended. Methods. In the present study, twelve patients were included, with
      insufficient alveolar ridge widths in the designated sites for dental implant
      placement. During the primary surgery, mineralized corticocancellous block
      allografts were fixed in deficient sites with titanium screws and resorbable
      collagen membranes were used to cover the blocks. After a period of six months, a
      flap was raised and variations in ridge width values was measured. Finally, a
      micro-biopsy was obtained from the sites for histologic investigation prior to
      preparing them for subsequent implant placement. Results. All the applied blocks
      were incorporated into the underlying bone except for one. A statistically
      significant difference was seen between the average ridge widths before placing
      the allografts compared with that of implant placement stage (2.62+/-1.02 mm vs.
      7.75+/-1.63 mm, respectively). Vital bone tissue was detected in all the
      histological specimens obtained from the interface of blocks and the underlying
      bone. Conclusion. The results suggest that mineralized corticocancellous block
      allografts might be used as scaffolds for bone growth and ridge width
      augmentation.

PMID- 29354252
TI  - Effect of stress, anxiety and depression on unstimulated salivary flow rate and
      xerostomia.
AB  - Background. Unstimulated salivary flow rate can be influenced by different
      factors. This study was undertaken to evaluate the effect of stress, anxiety and
      depression on unstimulated salivary flow rate in adults. Methods. A total of 247
      adult subjects, randomly selected from patients referring to Zanjan Dental
      School, were included in this investigation. The study procedures consisted of
      collecting salivary samples (in 5 minutes), completing a form for feeling of
      xerostomia and completing Depression Anxiety Stress Scale (DASS) Questionnaire to
      assess the severity of stress, anxiety and depression. Based on the results, the
      patients were categorized in four groups: Low salivary flow rate plus xerostomia
      (group 1, n=60), normal salivary flow rate plus xerostomia (group 2, n=59), low
      salivary flow rate without xerostomia (group 3, n=60) and normal salivary flow
      rate without xerostomia (control group, n=68). Results. The frequencies of
      subjects with severe and major depression in groups 1, 2 and 3 were 31.4%, 11.7%
      and 8.5%, respectively, with 4.4% in the control group. The frequencies of
      subjects with severe stress in groups 1, 2 and 3 were 21.7%, 3.3% and 11.9%,
      respectively, with 1.5% in the control group. The frequencies of patients with
      severe anxiety in groups 1, 2 and 3 were 50%, 30% and 61.1%, respectively, with
      4.4% in the control group. Stress, anxiety and depression exhibited a
      statistically significant relationship with unstimulated salivary flow rate and
      xerostomia (P<0.05). Conclusion. Stress, anxiety and depression can influence
      unstimulated salivary flow rate and lead to xerostomia.

PMID- 29354251
TI  - Bending resistance and cyclic fatigue life of Reciproc Blue, WaveOne Gold, and
      Genius files in a double (S-shaped) curved canal.
AB  - Background. This study compared the cyclic fatigue resistance, bending resistance
      and cross-sectional areas of Reciproc Blue (RPC Blue), WaveOne Gold (WOG), and
      Genius File (GF) NiTi rotary systems. Methods. Forty RPC Blue R25 (25/.08), 40
      WOG Primary (25/.07) and 40 GF (25/.04) files were used in the present study.
      Flexibility of the files was determined by 45 degrees  bending test. The
      instruments were also subjected to cyclic fatigue resistance, calculating the
      number of cycles to fracture (NCF) in an S-shaped artificial stainless steel
      canal. Also the cross-sectional areas of the files were measured at D5 level. The
      length of the fractured file tips was measured. The fracture surface of all the
      fragments was examined with a scanning electron microscope. Data was
      statistically analyzed using one-way ANOVA and post hoc Tukey tests. Results. In
      both the apical and coronal curvatures, the NCF of the GF was significantly
      higher than that of the RPC Blue and WOG files. There was no significant
      difference between the GF, WOG and Reciproc Blue files with respect to the
      lengths of the fractured file fragments in either the apical or coronal
      curvature. The bending resistance of the GF was signif-icantly higher than that
      of the RPC Blue and WOG files. The RPC Blue had the largest cross-sectional area,
      and the GF had the smallest cross-sectional area. Conclusion. Within the
      limitations of the present study, the GF NiTi system exhibited the highest cyclic
      and bending re-sistance among the experimental groups.

PMID- 29354253
TI  - A single visit feeding plate for 3 months old cleft palate infant . A case
      report.
AB  - Infants with cleft palate (CP) suffer from several difficulties, one of them is
      feeding, which prevent infant from maintaining adequate nutrition. Usage of
      feeding plate, special bottles and nipples has been described to overcome this
      problem. This article describes steps of constructing a single visit feeding
      plate for a CP infant. The main objective was to provide an infant with a
      properly functioning feeding prosthesis and to reduce parents' anxiety originated
      from multiple dental visits. We can conclude that our feeding plate was
      successfully achieving the planned objectives.

PMID- 29354254
TI  - Effect of local injection of Zolena, zoledronic acid made in Iran, on orthodontic
      tooth movement and root and bone resorption in rats.
AB  - Background. Anchorage control is an essential part of orthodontic treatment
      planning, especially in adult patients who demand a more convenient treatment.
      Zoledronic acid (ZA) is an effective choice to address this problem. It is the
      most potent member of the bisphosphonates family that has an inhibitory effect on
      bone resorption by suppressing osteoclast function. Therefore, ZA might be a good
      option for orthodontic anchorage control. The current study evaluated the effect
      of local administration of Zolena (ZA made in Iran) on orthodontic tooth movement
      (OTM) and root and bone resorption. Methods. The experimental group consisted of
      30 rats in 3 subgroups (n=10). Anesthesia was induced, and one closed NiTi coil
      spring was installed between the first molar and central incisor unilaterally,
      except for the negative control group. The positive control group received
      vestibular injection of 0.01 mL of saline next to the maxillary first molar, and
      0.01 mL of the solution was injected at the same site in the ZA group. After 21
      days, the rats were sacrificed and the distance between the first and second
      molars was measured with a leaf gauge. Histological analysis was conducted by a
      blind pathologist for the number of Howship's lacunae, blood vessels, osteoclast
      like cells and root resorption lacunae. Data were analyzed with ANOVA, Tukey test
      and t-test. Results. There were no significant differences in OTM between the
      force-applied groups. ZA significantly inhibited bone/root resorption and
      angiogenesis compared to the positive control group. Conclusion. Zolena did not
      decrease OTM but significantly inhibited bone and root resorption. Zolena might
      be less potent than its foreign counterparts.

PMID- 29354256
TI  - Erratum to: Comparison of bracket bond strength to etched and unetched enamel
      under dry and wet conditions using Fuji Ortho LC glass-ionomer.
AB  - [This corrects the article DOI: 10.15171/joddd.2017.006.].

PMID- 29354255
TI  - Propolis: A natural biomaterial for dental and oral healthcare.
AB  - The field of health has always emphasised on the use of natural products for
      curing diseases. There are varieties of natural products (such as silk, herbal
      tea, chitosan) used today in the biomedical application in treating a large array
      of systemic diseases. The natural product "Propolis" is a non-toxic resinous
      material having beneficial properties such as antimicrobial, anticancer,
      antifungal, antiviral and anti-inflammatory; hence gain the attention of
      researchers for its potential for bio-dental applications. The study aims to
      explore the properties and chemistry of propolis concerning biomedical and dental
      applications. In addition, status and scope of propolis for current and potential
      future in bio-dental applications have been discussed. This review gives an
      insight to the reader about the possible use of propolis in modern-day dentistry.

PMID- 29354257
TI  - Drought effects on the tissue- and cell-specific cytokinin activity in poplar.
AB  - Climate change with increasing periods of drought is expected to reduce the yield
      of biomass crops such as poplars. To combat yield loss, it is important to better
      understand the molecular mechanisms that control growth under drought. Here, the
      goal was to resolve the drought-induced changes of active cytokinins, a main
      growth hormone in plants, at the tissue level in different cell types and organs
      of poplars (Populus * canescens) in comparison with growth, biomass, leaf
      shedding, photosynthesis and water potential. Since cytokinin response is
      mediated by type-A response regulators, ARR5::GUS reporter lines were used to map
      cytokinin activity histochemically. The expression of PtaRR3 and PtaRR10 was
      examined in different stem sections. Young leaves showed strong cytokinin
      activity in the veins and low staining under drought stress, accompanied by
      diminished leaf expansion. Leaf scars, at positions where drought-shedding
      occurred, showed strong reduction of cytokinin activity. The pith in the
      differentiation zone of stem showed high cytokinin activity with distinct, very
      active parenchymatic cells and enhanced activity close to primary xylem. This
      pattern was maintained under drought but the cytokinin activity was reduced.
      Mature phloem parenchymatic cells showed high cytokinin activity and mature wood
      showed no detectable cytokinin activity. Cytokinin activity in the cambium was
      apparent as a clear ring, which faded under drought. Xylem-localized cytokinin
      activities were also mirrored by the relative expression of PtaRR3, whereas
      PtaRR10 showed developmental but no drought-induced changes. Primary meristems
      exhibited high cytokinin activity regardless of drought stress, supporting a
      function of this phytohormone in meristem maintenance, whereas declining
      cytokinin activities in apical pith tissues and cambium of drought-stressed
      poplars linked cytokinin in these cell types with the control of primary and
      secondary growth processes. Changes in cytokinin activity further imply a role in
      drought avoidance mechanisms of poplars, especially in the reduction of leaf
      area.

PMID- 29354258
TI  - Leaf thermotolerance in dry tropical forest tree species: relationships with leaf
      traits and effects of drought.
AB  - Understanding how tropical trees will respond to extreme temperatures and drought
      is essential to predict how future increases in the severity, frequency and
      duration of extreme climatic events will affect tropical systems. In this study,
      we investigated leaf thermotolerance by quantifying the temperatures that
      resulted in a 50 % decrease in photosystem II function (T50) in experimentally
      grown saplings of 12 tree species from a seasonally dry tropical forest. We
      examined the relationship of thermotolerance with leaf functional traits and
      photosynthetic rates. Additionally, we tested how water limitation altered
      thermotolerance within species, and examined the relationship between
      thermotolerance and drought tolerance among species. Thermotolerance ranged from
      44.5 to 48.1  degrees C in the least and most thermotolerant species,
      respectively. The observed variation in thermotolerance indicates that the upper
      limits of leaf function are critically close to maximum temperatures in this
      region, and that these species will be vulnerable to, and differentially affected
      by, future warming. Drought increased temperature tolerance, and species that
      were more drought tolerant were also more thermotolerant. Importantly,
      thermotolerance was positively related to the key leaf functional trait-leaf mass
      per area (LMA), and congruent with this, negatively related to photosynthetic
      rates. These results indicate that more productive species with lower LMA and
      higher photosynthetic rates may be more vulnerable to heat and drought stress,
      and more likely to be negatively affected by future increases in extreme climatic
      events.

PMID- 29354259
TI  - Experiences of moral distress by privately hired companions in Ontario's long
      term care facilities.
AB  - Purpose: To explore long-term residential care provided by people other than the
      facilities' employees. Privately hired paid "companions" are effectively
      invisible in health services research and policy. This research was designed to
      address this significant gap. There is growing recognition that nursing staff in
      long-term care (LTC) residential facilities experience moral distress - a
      phenomenon in which one knows the ethically right action to take, but is
      systemically constrained from taking it. To date, there has been no discussion of
      the distressing experiences of companions in LTC facilities. This paper explores
      companions' moral distress. Design: Data was collected using weeklong rapid
      ethnographies in seven LTC facilities in Southern Ontario, Canada. A feminist
      political economy analytic framework was used in the research design and in the
      analysis of findings. Findings: Despite the differences in their work tasks and
      employment conditions, structural barriers can cause moral distress for
      companions. This mirrors the impacts experienced by nurses that are highlighted
      in the literature. Though companions are hired in order to fill care gaps in the
      LTC system, they too struggle with the current system's limitations. The hiring
      of private companions is not a sustainable or equitable solution to under
      staffing and under-funding in Canada's LTC facilities. Value: Recognizing moral
      distress and the impact that it has on those providing LTC is critical in terms
      of supporting and protecting vulnerable and precarious care workers and ensuring
      high quality care for Canadians in LTC.

PMID- 29354261
TI  - Guest editorial: special issue on "Artificial Intelligence in Health and
      Medicine".

PMID- 29354260
TI  - Developmental Windows of Susceptibility to Inorganic Arsenic: A Survey of Current
      Toxicologic and Epidemiologic Data.
AB  - Globally, millions of people are exposed to elevated levels of inorganic arsenic
      (iAs) via drinking water. Exposure to iAs is associated with a wide range of
      negative health outcomes, including cancers, skin lesions, neurological
      impairment, cardiovascular diseases, and an increased susceptibility to
      infection. Among those exposed to iAs, the developing fetus and young children
      represent particularly sensitive subpopulations. Specifically, it has been noted
      in animal models and human populations that prenatal and early life iAs exposures
      are associated with diseases occurring during childhood and later in life. Recent
      epidemiologic and toxicologic studies have also demonstrated that epigenetic
      alterations may play a key mechanistic role underlying many of the iAs-associated
      health outcomes, including the carcinogenic and immunologic effects of exposure.
      This review summarizes some of the key studies related to prenatal and early life
      iAs exposure and highlights the complexities in isolating the precise
      developmental windows of exposure associated with these health outcomes.

PMID- 29354262
TI  - Local environmental quality positively predicts breastfeeding in the UK's
      Millennium Cohort Study.
AB  - Background and Objectives: Breastfeeding is an important form of parental
      investment with clear health benefits. Despite this, rates remain low in the UK;
      understanding variation can therefore help improve interventions. Life history
      theory suggests that environmental quality may pattern maternal investment,
      including breastfeeding. We analyse a nationally representative dataset to test
      two predictions: (i) higher local environmental quality predicts higher
      likelihood of breastfeeding initiation and longer duration; (ii) higher
      socioeconomic status (SES) provides a buffer against the adverse influences of
      low local environmental quality. Methodology: We ran factor analysis on a wide
      range of local-level environmental variables. Two summary measures of local
      environmental quality were generated by this analysis-one 'objective' (based on
      an independent assessor's neighbourhood scores) and one 'subjective' (based on
      respondent's scores). We used mixed-effects regression techniques to test our
      hypotheses. Results: Higher objective, but not subjective, local environmental
      quality predicts higher likelihood of starting and maintaining breastfeeding over
      and above individual SES and area-level measures of environmental quality. Higher
      individual SES is protective, with women from high-income households having
      relatively high breastfeeding initiation rates and those with high status jobs
      being more likely to maintain breastfeeding, even in poor environmental
      conditions. Conclusions and Implications: Environmental quality is often vaguely
      measured; here we present a thorough investigation of environmental quality at
      the local level, controlling for individual- and area-level measures. Our
      findings support a shift in focus away from individual factors and towards
      altering the landscape of women's decision making contexts when considering
      behaviours relevant to public health.

PMID- 29354264
TI  - The structural science of functional materials.
AB  - The growing complexity of functional materials and the major challenges this
      poses to structural science are discussed. The diversity of structural materials
      science and the contributions that computation is making to the field are
      highlighted.

PMID- 29354263
TI  - Impact of structurally modifying hyaluronic acid on CD44 interaction.
AB  - CD44 is a widely-distributed type I transmembrane glycoprotein that binds
      hyaluronic acid (HA) in most cell types, including primary tumor cells and cancer
      initiating cells and has roles in cell migration, cell-cell, and cell-matrix
      adhesion. HA-derived conjugates and nanoparticles that target the CD44 receptor
      on cells have been reported for targeted delivery of therapeutics and imaging
      agents. Altering crucial interactions of HA with CD44 active sites holds
      significant importance in modulating targeting ability of hyaluronic acid to
      other cancer types that do not express the CD44 receptor or minimizing the
      interaction with CD44+ cells that are not target cells. The approach adopted here
      was deacetylation of the N-acetyl group and selective sulfation on the C6-OH on
      the HA polymer, which form critical interactions with the CD44 active site. Major
      interactions identified by molecular modeling were confirmed to be hydrogen
      bonding of the C6-OH with Tyr109 and hydrophobic interaction of the N-acetyl
      group with Tyr46, 83 and Ile 92. Modified HA was synthesized and characterized
      and its interactions were assessed by in vitro and molecular modeling approaches.
      In vitro techniques included flow cytometry and fluorescence polarization, while
      in silico approaches included docking and binding calculations by a MM-PBSA
      approach. These studies indicated that while both deacetylation and sulfation of
      HA individually decrease CD44 interaction, both chemical modifications are
      required to minimize interaction with CD44+ cells. The results of this study
      represent the first step to effective retargeting of HA-derived NPs for imaging
      and drug delivery.

PMID- 29354265
TI  - Carbonic anhydrase under pressure.
AB  - Investigations of the rapid enzyme carbonic anhydrase have now been extended by
      crystallographic analysis at high CO2 pressures to examine the movements of water
      molecules in different steps of the catalysis. The rate of catalysis seems well
      explained by the assembled observations.

PMID- 29354267
TI  - Building inorganic supramolecular architectures using principles adopted from the
      organic solid state.
AB  - In order to develop transferable and practical avenues for the assembly of
      coordination complexes into architectures with specific dimensionality, a
      strategy utilizing ligands capable of simultaneous metal coordination and self
      complementary hydrogen bonding is presented. The three ligands used, 2(1H)
      pyrazinone, 4(3H)-pyrimidinone and 4(3H)-quinazolinone, consistently deliver the
      required synthetic vectors in a series of CdII coordination polymers, allowing
      for reproducible supramolecular synthesis that is insensitive to the different
      steric and geometric demands from potentially disruptive counterions. In all nine
      crystallographically characterized compounds presented here, directional
      intermolecular N-H?O hydrogen bonds between ligands on adjacent complex building
      blocks drive the assembly and orientation of discrete building blocks into
      largely predictable topologies. Furthermore, whether the solids are prepared from
      solution or through liquid-assisted grinding, the structural outcome is the same,
      thus emphasizing the robustness of the synthetic protocol. The details of the
      molecular recognition events that take place in this series of compounds have
      been clearly delineated and rationalized in the context of calculated molecular
      electrostatic potential surfaces.

PMID- 29354266
TI  - Hydrogen bonds in crystalline d-alanine: diffraction and spectroscopic evidence
      for differences between enantiomers.
AB  - Enantiomeric amino acids have specific physiological functions in complex
      biological systems. Systematic studies focusing on the solid-state properties of
      d-amino acids are, however, still limited. To shed light on this field,
      structural and spectroscopic studies of d-alanine using neutron powder
      diffraction, polarized Raman scattering and ab initio calculations of harmonic
      vibrational frequencies were carried out. Clear changes in the number of
      vibrational modes are observed as a function of temperature, which can be
      directly connected to variations of the N-D bond lengths. These results reveal
      dissimilarities in the structural properties of d-alanine compared with l
      alanine.

PMID- 29354268
TI  - An unprecedented dioxygen species revealed by serial femtosecond rotation
      crystallography in copper nitrite reductase.
AB  - Synchrotron-based X-ray structural studies of ligand-bound enzymes are powerful
      tools to further our understanding of reaction mechanisms. For redox enzymes, it
      is necessary to study both the oxidized and reduced active sites to fully
      elucidate the reaction, an objective that is complicated by potential X-ray
      photoreduction. In the presence of the substrate, this can be exploited to
      construct a structural movie of the events associated with catalysis. Using the
      newly developed approach of serial femtosecond rotation crystallography (SF-ROX),
      an X-ray damage-free structure of the as-isolated copper nitrite reductase
      (CuNiR) was visualized. The sub-10 fs X-ray pulse length from the SACLA X-ray
      free-electron laser allowed diffraction data to be collected to 1.6 A resolution
      in a 'time-frozen' state. The extremely short duration of the X-ray pulses
      ensures the capture of data prior to the onset of radiation-induced changes,
      including radiolysis. Unexpectedly, an O2 ligand was identified bound to the T2Cu
      in a brand-new binding mode for a diatomic ligand in CuNiRs. The observation of
      O2 in a time-frozen structure of the as-isolated oxidized enzyme provides long
      awaited clear-cut evidence for the mode of O2 binding in CuNiRs. This provides an
      insight into how CuNiR from Alcaligenes xylosoxidans can function as an oxidase,
      reducing O2 to H2O2, or as a superoxide dismutase (SOD) since it was shown to
      have ~56% of the dismutase activity of the bovine SOD enzyme some two decades
      ago.

PMID- 29354269
TI  - Probing the accuracy and precision of Hirshfeld atom refinement with HARt
      interfaced with Olex2.
AB  - Hirshfeld atom refinement (HAR) is a novel X-ray structure refinement technique
      that employs aspherical atomic scattering factors obtained from stockholder
      partitioning of a theoretically determined tailor-made static electron density.
      HAR overcomes many of the known limitations of independent atom modelling (IAM),
      such as too short element-hydrogen distances, r(X-H), or too large atomic
      displacement parameters (ADPs). This study probes the accuracy and precision of
      anisotropic hydrogen and non-hydrogen ADPs and of r(X-H) values obtained from
      HAR. These quantities are compared and found to agree with those obtained from
      (i) accurate neutron diffraction data measured at the same temperatures as the X
      ray data and (ii) multipole modelling (MM), an established alternative method for
      interpreting X-ray diffraction data with the help of aspherical atomic scattering
      factors. Results are presented for three chemically different systems: the
      aromatic hydro-carbon rubrene (orthorhombic 5,6,11,12-tetra-phenyl-tetracene), a
      co-crystal of zwitterionic betaine, imidazolium cations and picrate anions
      (BIPa), and the salt potassium hydrogen oxalate (KHOx). The non-hydrogen HAR-ADPs
      are as accurate and precise as the MM-ADPs. Both show excellent agreement with
      the neutron-based values and are superior to IAM-ADPs. The anisotropic hydrogen
      HAR-ADPs show a somewhat larger deviation from neutron-based values than the
      hydrogen SHADE-ADPs used in MM. Element-hydrogen bond lengths from HAR are in
      excellent agreement with those obtained from neutron diffraction experiments,
      although they are somewhat less precise. The residual density contour maps after
      HAR show fewer features than those after MM. Calculating the static electron
      density with the def2-TZVP basis set instead of the simpler def2-SVP one does not
      improve the refinement results significantly. All HARs were performed within the
      recently introduced HARt option implemented in the Olex2 program. They are easily
      launched inside its graphical user interface following a conventional IAM.

PMID- 29354270
TI  - Snapshot and crystallographic observations of kinetic and thermodynamic products
      for NO2S2 macrocyclic complexes.
AB  - Direct observation and structural characterization of a kinetic product and a
      thermodynamic product for complexes with an NO2S2 macrocycle (L) are reported. L
      reacts with copper(I) iodide to give a mononuclear complex
      [Cu(L)]2(Cu2I4).2CH2Cl2 (1), featuring three separate units. When cadmium(II)
      iodide was reacted with L, an anion-coordinated complex [Cd(L)I]2(Cd2I6).4CH3CN
      (2) with a needle-type crystal shape was formed as the kinetic product.
      Interestingly, when the needle-type kinetic product was left undisturbed in the
      mother solution it gradually transformed to the pseudo-dimer complex
      [Cd2(L)2I2](Cd2I6) (3) with a brick-type crystal shape as the thermodynamic
      product. The dissolution-recrystallization process resulted in the elimination of
      the lattice solvent molecules (aceto-nitrile) in 2 and the contraction of two
      neighboring macrocyclic complex units [Cd(L)I]+, forming the pseudo-dimer 3via an
      intermolecular Cd?I interaction between two monomers. For the entire process from
      kinetic to thermodynamic products, it was possible to obtain sequential
      photographic snapshots, single-crystal X-ray structures and powder X-ray
      diffraction patterns. For the copper(I) and cadmium(II) complexes, competitive
      NMR results agree with the solid-state data that show copper(I) has a higher
      affinity for L than does cadmium(II).

PMID- 29354271
TI  - Phase transition and magnetocaloric properties of Mn50Ni42-x Co x Sn8 (0 <= x <=
      10) melt-spun ribbons.
AB  - The characteristics of magnetostructural coupling play a crucial role in the
      magnetic field-driven behaviour of magnetofunctional alloys. The availability of
      magnetostructural coupling over a broad temperature range is of great
      significance for scientific and technological purposes. This work demonstrates
      that strong magnetostrucural coupling can be achieved over a wide temperature
      range (222 to 355 K) in Co-doped high Mn-content Mn50Ni42-x Co x Sn8 (0 <= x <=
      10) melt-spun ribbons. It is shown that, over a wide composition range with Co
      content from 3 to 9 at.%, the paramagnetic austenite first transforms into
      ferromagnetic austenite at TC on cooling, then the ferromagnetic austenite
      further transforms into a weakly magnetic martensite at TM. Such strong
      magnetostructural coupling enables the ribbons to exhibit field-induced inverse
      martensitic transformation behaviour and a large magnetocaloric effect. Under a
      field change of 5 T, a maximum magnetic entropy change DeltaSM of 18.6 J kg-1 K-1
      and an effective refrigerant capacity RCeff of up to 178 J kg-1 can be achieved,
      which are comparable with or even superior to those of Ni-rich Ni-Mn-based
      polycrystalline bulk alloys. The combination of high performance and low cost
      makes Mn-Ni-Co-Sn ribbons of great interest as potential candidates for magnetic
      refrigeration.

PMID- 29354272
TI  - Determination of atomic vacancies in InAs/GaSb strained-layer superlattices by
      atomic strain.
AB  - Determining vacancy in complex crystals or nanostructures represents an
      outstanding crystallographic problem that has a large impact on technology,
      especially for semiconductors, where vacancies introduce defect levels and modify
      the electronic structure. However, vacancy is hard to locate and its structure is
      difficult to probe experimentally. Reported here are atomic vacancies in the
      InAs/GaSb strained-layer superlattice (SLS) determined by atomic-resolution
      strain mapping at picometre precision. It is shown that cation and anion
      vacancies in the InAs/GaSb SLS give rise to local lattice relaxations, especially
      the nearest atoms, which can be detected using a statistical method and confirmed
      by simulation. The ability to map vacancy defect-induced strain and identify its
      location represents significant progress in the study of vacancy defects in
      compound semiconductors.

PMID- 29354273
TI  - Local-scale structures across the morphotropic phase boundary in PbZr1-x Ti x O3.
AB  - Lead zirconate titanate (PZT) is one of the most widely studied piezoelectric
      materials, mainly because of its 'mysterious' relationship between the so-called
      morphotropic phase boundary (MPB) and its strong piezoelectric coupling factor.
      Using results from a pair distribution function analysis, this paper examines how
      the complex local structure in PZT affects the long-range average structure
      across the MPB. A monoclinic M C type structure is discovered in PZT. A first
      order transformation between the monoclinic M A and M C components in both the
      average and local structures explains the sudden change in piezoelectric effect
      around these compositions. The role of polarization rotation in the enhancement
      of the piezoelectric properties is discussed with respect to the composition of
      PZT. The structure-property relationship that is revealed by this study explains
      the unique properties of PZT, and may be applicable in the design of new MPB-type
      functional materials.

PMID- 29354274
TI  - Crystal structure of peroxiredoxin 3 from Vibrio vulnificus and its implications
      for scavenging peroxides and nitric oxide.
AB  - Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidase enzymes. Recently,
      a new type of Prx, VvPrx3, was identified in the pathogenic bacterium Vibrio
      vulnificus as being important for survival in macrophages. It employs only one
      catalytic cysteine residue to decompose peroxides. Here, crystal structures of
      VvPrx3 representing its reduced and oxidized states have been determined,
      together with an H2O2-bound structure, at high resolution. The crystal structure
      representing the reduced Prx3 showed a typical dimeric interface, called the A
      type interface. However, VvPrx3 forms an oligomeric interface mediated by a
      disulfide bond between two catalytic cysteine residues from two adjacent dimers,
      which differs from the doughnut-like oligomers that appear in most Prxs.
      Subsequent biochemical studies showed that this disulfide bond was induced by
      treatment with nitric oxide (NO) as well as with peroxides. Consistently, NO
      treatment induced expression of the prx3 gene in V. vulnificus, and VvPrx3 was
      crucial for the survival of bacteria in the presence of NO. Taken together, the
      function and mechanism of VvPrx3 in scavenging peroxides and NO stress via
      oligomerization are proposed. These findings contribute to the understanding of
      the diverse functions of Prxs during pathogenic processes at the molecular level.

PMID- 29354275
TI  - Active-site solvent replenishment observed during human carbonic anhydrase II
      catalysis.
AB  - Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the
      reversible hydration/dehydration of CO2/HCO3-. Although hCA II has been
      extensively studied to investigate the proton-transfer process that occurs in the
      active site, its underlying mechanism is still not fully understood. Here,
      ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO2
      pressures of 7.0 and 2.5 atm are presented. The structures reveal new
      intermediate solvent states of hCA II that provide crystallographic snapshots
      during the restoration of the proton-transfer water network in the active site.
      Specifically, a new intermediate water (WI') is observed next to the previously
      observed intermediate water WI, and they are both stabilized by the five water
      molecules at the entrance to the active site (the entrance conduit). Based on
      these structures, a water network-restructuring mechanism is proposed, which
      takes place at the active site after the nucleophilic attack of OH- on CO2. This
      mechanism explains how the zinc-bound water (WZn) and W1 are replenished, which
      are directly responsible for the reconnection of the His64-mediated proton
      transfer water network. This study provides the first 'physical' glimpse of how a
      water reservoir flows into the hCA II active site during its catalytic activity.

PMID- 29354276
TI  - Resolution extension by image summing in serial femtosecond crystallography of
      two-dimensional membrane-protein crystals.
AB  - Previous proof-of-concept measurements on single-layer two-dimensional membrane
      protein crystals performed at X-ray free-electron lasers (FELs) have demonstrated
      that the collection of meaningful diffraction patterns, which is not possible at
      synchrotrons because of radiation-damage issues, is feasible. Here, the results
      obtained from the analysis of a thousand single-shot, room-temperature X-ray FEL
      diffraction images from two-dimensional crystals of a bacteriorhodopsin mutant
      are reported in detail. The high redundancy in the measurements boosts the
      intensity signal-to-noise ratio, so that the values of the diffracted intensities
      can be reliably determined down to the detector-edge resolution of 4 A. The
      results show that two-dimensional serial crystallography at X-ray FELs is a
      suitable method to study membrane proteins to near-atomic length scales at
      ambient temperature. The method presented here can be extended to pump-probe
      studies of optically triggered structural changes on submillisecond timescales in
      two-dimensional crystals, which allow functionally relevant large-scale motions
      that may be quenched in three-dimensional crystals.

PMID- 29354277
TI  - A novel de novo mutation in COL2A1 leading to spondyloepiphyseal dysplasia
      congenita in a Chinese family.
AB  - Spondyloepiphyseal dysplasia congenita (SEDC) is an extremely rare autosomal
      dominant chondrodysplasia that is usually caused by substitution of glycine with
      another amino acid in the triple helical region of COL2A1. Herein, we describe a
      case of SEDC in a Chinese family with a novel de novo mutation in the COL2A1
      gene, c.1150G>A (p.Gly384Ser), which may impair protein stability and lead to
      dysfunction of type II collagen.

PMID- 29354278
TI  - Development of the Human Factors Skills for Healthcare Instrument: a valid and
      reliable tool for assessing interprofessional learning across healthcare practice
      settings.
AB  - Background: A central feature of clinical simulation training is human factors
      skills, providing staff with the social and cognitive skills to cope with
      demanding clinical situations. Although these skills are critical to safe patient
      care, assessing their learning is challenging. This study aimed to develop, pilot
      and evaluate a valid and reliable structured instrument to assess human factors
      skills, which can be used pre- and post-simulation training, and is relevant
      across a range of healthcare professions. Method: Through consultation with a
      multi-professional expert group, we developed and piloted a 39-item survey with
      272 healthcare professionals attending training courses across two large
      simulation centres in London, one specialising in acute care and one in mental
      health, both serving healthcare professionals working across acute and community
      settings. Following psychometric evaluation, the final 12-item instrument was
      evaluated with a second sample of 711 trainees. Results: Exploratory factor
      analysis revealed a 12-item, one-factor solution with good internal consistency
      (alpha=0.92). The instrument had discriminant validity, with newly qualified
      trainees scoring significantly lower than experienced trainees (t(98)=4.88,
      p<0.001) and was sensitive to change following training in acute and mental
      health settings, across professional groups (p<0.001). Confirmatory factor
      analysis revealed an adequate model fit (RMSEA=0.066). Conclusion: The Human
      Factors Skills for Healthcare Instrument provides a reliable and valid method of
      assessing trainees' human factors skills self-efficacy across acute and mental
      health settings. This instrument has the potential to improve the assessment and
      evaluation of human factors skills learning in both uniprofessional and
      interprofessional clinical simulation training.

PMID- 29354279
TI  - Evaluation of a multiple-encounter in situ simulation for orientation of staff to
      a new paediatric emergency service: a single-group pretest/post-test study.
AB  - Aim: To assess the utility of a multiple-encounter in-situ (MEIS) simulation as
      an orientation tool for multidisciplinary staff prior to opening a new paediatric
      emergency service. Methods: A single-group pretest/post-test study was conducted.
      During the MEIS simulation, multidisciplinary staff with participant or observer
      roles managed eight children (mannequins) who attended triage with their
      parent/guardians (clinical facilitators) for a range of emergency presentations
      (structured scenarios designed to represent the expected range of presentations
      plus test various clinical pathways/systems). Participants were debriefed to
      explore clinical, systems and crisis-resource management issues. Participants
      also completed a pre-intervention and post-intervention questionnaire comprising
      statements about role confidence and orientation adequacy. Pre-test and post-test
      results were analysed using t-test and Wilcoxon signed rank test. Results: Eighty
      nine staff participated in the MEIS simulation, with the majority completing the
      pre-simulation and post-simulation questionnaire. There was a significant
      improvement in post-intervention versus pre-intervention Likert scores for role
      confidence and orientation adequacy (p=0.001 and <0.001, respectively); effect
      sizes suggested the greatest impact was on orientation adequacy. Nearly all
      scenarios resulted in significant increases in participants' confidence levels.
      Conclusions: The MEIS simulation was of utility in orientation of staff, at least
      with respect to self-reported role confidence and orientation adequacy. Its
      effectiveness in practice or compared with other orientation techniques was not
      assessed, but it did identify several flaws in planned systems allowing
      remediation prior to opening.

PMID- 29354280
TI  - Medical judgement analogue studies with applications to spaceflight crew medical
      officer.
AB  - Background: The National Aeronautics and Space Administration (NASA) developed
      plans for potential emergency conditions from the Exploration Medical Conditions
      List. In an effort to mitigate conditions on the Exploration Medical Conditions
      List, NASA implemented a crew medical officer (CMO) designation for eligible
      astronauts. This pilot study aims to add knowledge that could be used in the
      Integrated Medical Model. Methods: An analogue population was recruited for two
      categories: administrative physicians (AP) representing the physician CMOs and
      technical professionals (TP) representing the non-physician CMOs. Participants
      completed four medical simulations focused on abdominal pain: cholecystitis (CH)
      and renal colic (RC) and chest pain: cardiac ischaemia (STEMI; ST-segment
      elevation myocardial infarction) and pneumothorax (PX). The Medical Judgment
      Metric (MJM) was used to evaluate medical decision making. Results: There were no
      significant differences between the AP and TP groups in age, gender, race,
      ethnicity, education and baseline heart rate. Significant differences were noted
      in MJM average rater scores in AP versus TP in CH: 13.0 (+/-2.25), 4.5 (+/-0.48),
      p=<0.001; RC: 12.3 (+/-2.66), 4.8 (+/-0.94); STEMI: 12.1 (+/-3.33), 4.9 (+/
      0.56); and PX: 13.5 (+/-2.53), 5.3 (+/-1.01), respectively. Discussion: There
      could be a positive effect on crew health risk by having a physician CMO. The MJM
      demonstrated the ability to quantify medical judgement between the two analogue
      groups of spaceflight CMOs. Future studies should incorporate the MJM in a larger
      analogue population study to assess the medical risk for spaceflight crewmembers.

PMID- 29354281
TI  - 3D printing materials and their use in medical education: a review of current
      technology and trends for the future.
AB  - 3D printing is a new technology in constant evolution. It has rapidly expanded
      and is now being used in health education. Patient-specific models with
      anatomical fidelity created from imaging dataset have the potential to
      significantly improve the knowledge and skills of a new generation of surgeons.
      This review outlines five technical steps required to complete a printed model:
      They include (1) selecting the anatomical area of interest, (2) the creation of
      the 3D geometry, (3) the optimisation of the file for the printing and the
      appropriate selection of (4) the 3D printer and (5) materials. All of these steps
      require time, expertise and money. A thorough understanding of educational needs
      is therefore essential in order to optimise educational value. At present, most
      of the available printing materials are rigid and therefore not optimum for
      flexibility and elasticity unlike biological tissue. We believe that the
      manipuation and tuning of material properties through the creation of composites
      and/or blending materials will eventually allow for the creation of patient
      specific models which have both anatomical and tissue fidelity.

PMID- 29354282
TI  - Regulatory feedback response mechanisms to phosphate starvation in rice.
AB  - Phosphorus is a growth-limiting nutrient for plants. The growing scarcity of
      phosphate stocks threatens global food security. Phosphate-uptake regulation is
      so complex and incompletely known that attempts to improve phosphorus use
      efficiency have had extremely limited success. This study improves our
      understanding of the molecular mechanisms underlying phosphate uptake by
      investigating the transcriptional dynamics of two regulators: the Ubiquitin
      ligase PHO2 and the long non-coding RNA IPS1. Temporal measurements of RNA levels
      have been integrated into mechanistic mathematical models using advanced
      statistical techniques. Models based solely on current knowledge could not
      adequately explain the temporal expression profiles. Further modeling and
      bioinformatics analysis have led to the prediction of three regulatory features:
      the PHO2 protein mediates the degradation of its own transcriptional activator to
      maintain constant PHO2 mRNA levels; the binding affinity of the transcriptional
      activator of PHO2 is impaired by a phosphate-sensitive transcriptional
      repressor/inhibitor; and the extremely high levels of IPS1 and its rapid
      disappearance upon Pi re-supply are best explained by Pi-sensitive RNA
      protection. This work offers both new opportunities for plant phosphate research
      that will be essential for informing the development of phosphate efficient crop
      varieties, and a foundation for the development of models integrating phosphate
      with other stress responses.

PMID- 29354283
TI  - Regeneration in distantly related species: common strategies and pathways.
AB  - While almost all animals are able to at least partially replace some lost parts,
      regeneration abilities vary considerably across species. Here we study gene
      expression patterns in distantly related species to investigate conserved
      regeneration strategies. To this end, we collect from the literature
      transcriptomic data obtained during the regeneration of three species (Hydra
      magnipapillata, Schmidtea mediterranea, and Apostichopus japonicus), and compare
      them with gene expression during regeneration in vertebrates and mammals. This
      allows us to identify a common set of differentially expressed genes and relevant
      shared pathways that are conserved across species during the early stage of the
      regeneration process. We also find a set of differentially expressed genes that
      in mammals are associated to the presence of macrophages and to the epithelial
      mesenchymal transition. This suggests that features of the sophisticated wound
      healing strategy of mammals are already observable in earlier emerging metazoans.

PMID- 29354284
TI  - Mapping the operational landscape of microRNAs in synthetic gene circuits.
AB  - MicroRNAs are a class of short, noncoding RNAs that are ubiquitous modulators of
      gene expression, with roles in development, homeostasis, and disease. Engineered
      microRNAs are now frequently used as regulatory modules in synthetic biology.
      Moreover, synthetic gene circuits equipped with engineered microRNA targets with
      perfect complementarity to endogenous microRNAs establish an interface with the
      endogenous milieu at the single-cell level. The function of engineered microRNAs
      and sensor systems is typically optimized through extensive trial-and-error.
      Here, using a combination of synthetic biology experimentation in human embryonic
      kidney cells and quantitative analysis, we investigate the relationship between
      input genetic template abundance, microRNA concentration, and output under
      microRNA control. We provide a framework that employs the complete operational
      landscape of a synthetic gene circuit and enables the stepwise development of
      mathematical models. We derive a phenomenological model that recapitulates
      experimentally observed nonlinearities and contains features that provide insight
      into the microRNA function at various abundances. Our work facilitates the
      characterization and engineering of multi-component genetic circuits and
      specifically points to new insights on the operation of microRNAs as mediators of
      endogenous information and regulators of gene expression in synthetic biology.

PMID- 29354285
TI  - Handling variability and incompleteness of biological data by flexible nets: a
      case study for Wilson disease.
AB  - Mathematical models that combine predictive accuracy with explanatory power are
      central to the progress of systems and synthetic biology, but the heterogeneity
      and incompleteness of biological data impede our ability to construct such
      models. Furthermore, the robustness displayed by many biological systems means
      that they have the flexibility to operate under a range of physiological
      conditions and this is difficult for many modeling formalisms to handle. Flexible
      nets (FNs) address these challenges and represent a paradigm shift in model-based
      analysis of biological systems. FNs can: (i) handle uncertainties, ranges and
      missing information in concentrations, stoichiometry, network topology, and
      transition rates without having to resort to statistical approaches; (ii)
      accommodate different types of data in a unified model that integrates various
      cellular mechanisms; and (iii) be employed for system optimization and model
      predictive control. We present FNs and illustrate their capabilities by modeling
      a well-established system, the dynamics of glucose consumption by a microbial
      population. We further demonstrate the ability of FNs to take control actions in
      response to genetic or metabolic perturbations. Having bench-marked the system,
      we then construct the first quantitative model for Wilson disease-a rare genetic
      disorder that impairs copper utilization in the liver. We used this model to
      investigate the feasibility of using vitamin E supplementation therapy for
      symptomatic improvement. Our results indicate that hepatocytic inflammation
      caused by copper accumulation was not aggravated by limitations on endogenous
      antioxidant supplies, which means that treating patients with antioxidants is
      unlikely to be effective.

PMID- 29354286
TI  - Pan-cancer screen for mutations in non-coding elements with conservation and
      cancer specificity reveals correlations with expression and survival.
AB  - Cancer develops by accumulation of somatic driver mutations, which impact
      cellular function. Mutations in non-coding regulatory regions can now be studied
      genome-wide and further characterized by correlation with gene expression and
      clinical outcome to identify driver candidates. Using a new two-stage procedure,
      called ncDriver, we first screened 507 ICGC whole-genomes from 10 cancer types
      for non-coding elements, in which mutations are both recurrent and have elevated
      conservation or cancer specificity. This identified 160 significant non-coding
      elements, including the TERT promoter, a well-known non-coding driver element, as
      well as elements associated with known cancer genes and regulatory genes (e.g.,
      PAX5, TOX3, PCF11, MAPRE3). However, in some significant elements, mutations
      appear to stem from localized mutational processes rather than recurrent positive
      selection in some cases. To further characterize the driver potential of the
      identified elements and shortlist candidates, we identified elements where
      presence of mutations correlated significantly with expression levels (e.g., TERT
      and CDH10) and survival (e.g., CDH9 and CDH10) in an independent set of 505 TCGA
      whole-genome samples. In a larger pan-cancer set of 4128 TCGA exomes with
      expression profiling, we identified mutational correlation with expression for
      additional elements (e.g., near GATA3, CDC6, ZNF217, and CTCF transcription
      factor binding sites). Survival analysis further pointed to MIR122, a known
      marker of poor prognosis in liver cancer. In conclusion, the screen for
      significant mutation patterns coupled with correlative mutational analysis
      identified new individual driver candidates and suggest that some non-coding
      mutations recurrently affect expression and play a role in cancer development.

PMID- 29354289
TI  - New prize and features for Spinal Cord Series and Cases.

PMID- 29354288
TI  - Dielectric properties measurements of brown and white adipose tissue in rats from
      0.5 to 10 GHz.
AB  - Brown adipose tissue (BAT) plays an important role in whole body metabolism and
      with appropriate stimulus could potentially mediate weight gain and insulin
      sensitivity. Although imaging techniques are available to detect subsurface BAT,
      there are currently no viable methods for continuous acquisition of BAT energy
      expenditure. Microwave (MW) radiometry is an emerging technology that allows the
      quantification of tissue temperature variations at depths of several centimeters.
      Such temperature differentials may be correlated with variations in metabolic
      rate, thus providing a quantitative approach to monitor BAT metabolism. In order
      to optimize MW radiometry, numerical and experimental phantoms with accurate
      dielectric properties are required to develop and calibrate radiometric sensors.
      Thus, we present for the first time, the characterization of relative
      permittivity and electrical conductivity of brown (BAT) and white (WAT) adipose
      tissues in rats across the MW range 0.5-10GHz. Measurements were carried out in
      situ and post mortem in six female rats of approximately 200g. A Cole-Cole model
      was used to fit the experimental data into a parametric model that describes the
      variation of dielectric properties as a function of frequency. Measurements
      confirm that the dielectric properties of BAT (epsilonr = 14.0-19.4, sigma = 0.3
      3.3S/m) are significantly higher than those of WAT (epsilonr = 9.1-11.9, sigma =
      0.1-1.9S/m), in accordance with the higher water content of BAT.

PMID- 29354287
TI  - A robust targeted sequencing approach for low input and variable quality DNA from
      clinical samples.
AB  - Next-generation deep sequencing of gene panels is being adopted as a diagnostic
      test to identify actionable mutations in cancer patient samples. However,
      clinical samples, such as formalin-fixed, paraffin-embedded specimens, frequently
      provide low quantities of degraded, poor quality DNA. To overcome these issues,
      many sequencing assays rely on extensive PCR amplification leading to an
      accumulation of bias and artifacts. Thus, there is a need for a targeted
      sequencing assay that performs well with DNA of low quality and quantity without
      relying on extensive PCR amplification. We evaluate the performance of a targeted
      sequencing assay based on Oligonucleotide Selective Sequencing, which permits the
      enrichment of genes and regions of interest and the identification of sequence
      variants from low amounts of damaged DNA. This assay utilizes a repair process
      adapted to clinical FFPE samples, followed by adaptor ligation to single stranded
      DNA and a primer-based capture technique. Our approach generates sequence
      libraries of high fidelity with reduced reliance on extensive PCR amplification
      this facilitates the accurate assessment of copy number alterations in addition
      to delivering accurate single nucleotide variant and insertion/deletion
      detection. We apply this method to capture and sequence the exons of a panel of
      130 cancer-related genes, from which we obtain high read coverage uniformity
      across the targeted regions at starting input DNA amounts as low as 10 ng per
      sample. We demonstrate the performance using a series of reference DNA samples,
      and by identifying sequence variants in DNA from matched clinical samples
      originating from different tissue types.

PMID- 29354290
TI  - HIV-1-associated inflammation and antiretroviral therapy regulate astrocyte
      endoplasmic reticulum stress responses.
AB  - Antiretroviral (ARV) therapy (ART) has effectively suppressed the incidence of
      human immunodeficiency virus (HIV)-associated dementia in HIV-1 positive
      individuals. However, the prevalence of more subtle forms of neurocognitive
      dysfunction continues to escalate. Recently, endoplasmic reticulum (ER) stress
      has been linked to many neurological diseases; yet, its role in HIV/neuroAIDS
      remains largely unexplored. Furthermore, upregulation of astrocyte elevated gene
      1 (AEG-1), a novel HIV-1 inducible gene, along with ER stress markers in a
      Huntington's disease model, suggests a possible role in HIV-associated ER stress.
      The current study is focused on unfolded protein responses (UPRs) and AEG-1
      regulation in primary human astrocytes exposed to HIV-associated neurocognitive
      disorders (HAND)-relevant stimuli (HIV-1 virions, inflammation and ARV drugs).
      Interleukin (IL)-1beta and the nucleoside reverse transcriptase inhibitor
      abacavir upregulated expression of ER stress markers in human astrocytes,
      including binding immunoglobulin protein (BiP), C/EBP homologous protein (CHOP),
      and calnexin. In addition, IL-1beta activated all three well-known UPR pathways:
      protein kinase RNA-like ER kinase (PERK); activating transcription factor 6 (ATF
      6); and inositol-requiring enzyme 1alpha (IRE1alpha). AEG-1 upregulation
      correlated to ER stress and demonstrated astrocyte AEG-1 interaction with the
      calcium-binding chaperone, calnexin. IL-1beta and abacavir enhanced intracellular
      calcium signaling in astrocytes in the absence of extracellular calcium,
      illustrating ER-associated calcium release. Alternatively, calcium evoked in
      response to HAND-relevant stimuli led to mitochondrial permeability transition
      pore (mPTP) opening in human astrocytes. Importantly, IL-1beta- and abacavir
      induced UPR and mPTP opening were inhibited by the intracellular calcium
      chelation, indicating the critical role of calcium signaling in HAND-relevant ER
      stress in astrocytes. In summary, our study highlights that ARV drugs and IL
      1beta induced UPR, AEG-1 expression, intracellular calcium, and mitochondrial
      depolarization in astrocytes. This study uncovers astrocyte ER stress as a novel
      therapeutic target in the management of HIV-1-associated neurotoxicity and
      possibly in the treatment of neuroAIDS.

PMID- 29354291
TI  - Unacylated ghrelin prevents mitochondrial dysfunction in a model of
      ischemia/reperfusion liver injury.
AB  - Ischemia/reperfusion (I/R) injury is a common cause of liver dysfunction during
      hepatectomy, liver transplantation procedures and in generalized shock. Although
      effort has been dedicated to rescuing tissue damage in these clinical settings,
      there is still an urgent need for an effective treatment to protect the liver
      from the burden of I/R injury. In this study, we have investigated the potential
      clinical impact of unacylated-ghrelin (UnAG) in a liver I/R rat model. Particular
      attention has been paid to mitochondria. We demonstrate that UnAG was able to
      reduce the lag-phase time in response to ADP administration and increase oxygen
      consumption in ex vivo experiments using liver mitochondria recovered from rats
      subjected to I/R. Moreover, we found that UnAG rescued the expression of a key
      regulator of mitochondrial morphology and electron transport chain function; the
      optic atrophy 1 (Opa1) protein. Cytochrome c oxidase (COX), ATP synthase (complex
      V) activity and mitochondrial permeability transition pore (mPTP) opening were
      also affected by UnAG administration in vivo. An in vitro, hepatic I/R model was
      used to validate these data. We demonstrate that UnAG upregulates the expression
      of Cox subunit IV (CoxIV) and increases cellular ATP content. This results in Bcl
      2 upregulation and protection against apoptosis. Opa1 silencing shows that Opa1
      is crucial for a UnAG-induced increase in cellular ATP content, apoptosis
      resistance, Bcl-2 and CoxIV expression. Finally, we show that UnAG improves
      Opa1's interaction with MIC60 in the I/R setting, hinting at its role in cristae
      shape regulation. Our results demonstrate that UnAG administration rescues the
      intrinsic mitochondrial pathway triggered by I/R damage. Opa1's contribution in
      mediating this effect is also reported. This suggests that UnAG can interfere
      with mitochondrial dysfunction, via Opa1, in a preclinical liver I/R model. We
      therefore provide the rationale for exploiting UnAG as an alternative means to
      rescuing mitochondrial damage and organ dysfunction.

PMID- 29354292
TI  - Parthenolide prevents resistance of MDA-MB231 cells to doxorubicin and
      mitoxantrone: the role of Nrf2.
AB  - Triple-negative breast cancer is a group of aggressive cancers with poor
      prognosis owing to chemoresistance, recurrence and metastasis. New strategies are
      required that could reduce chemoresistance and increases the effectiveness of
      chemotherapy. The results presented in this paper, showing that parthenolide (PN)
      prevents drug resistance in MDA-MB231 cells, represent a contribution to one of
      these possible strategies. MDA-MB231 cells, the most studied line of TNBC cells,
      were submitted to selection treatment with mitoxantrone (Mitox) and doxorubicin
      (DOX). The presence of resistant cells was confirmed through the measurement of
      the resistance index. Cells submitted to this treatment exhibited a remarkable
      increment of NF-E2-related factor 2 (Nrf2) level, which was accompanied by
      upregulation of catalase, MnSOD, HSP70, Bcl-2 and P-glycoprotein. Moreover, as a
      consequence of overexpression of Nrf2 and correlated proteins, drug-treated cells
      exhibited a much lower ability than parental cells to generate ROS in response to
      a suitable stimulation. The addition of PN (2.0 MUM) to Mitox and DOX, over the
      total selection time, prevented both the induction of resistance and the
      overexpression of Nrf2 and correlated proteins, whereas the cells showed a good
      ability to generate ROS in response to adequate stimulation. To demonstrate that
      Nrf2 exerted a crucial role in the induction of resistance, the cells were
      transiently transfected with a specific small interfering RNA for Nrf2. Similarly
      to the effects induced by PN, downregulation of Nrf2 was accompanied by
      reductions in the levels of catalase, MnSOD, HSP70 and Bcl-2, prevention of
      chemoresistance and increased ability to generate ROS under stimulation. In
      conclusion, our results show that PN inhibited the development of the resistance
      toward Mitox and DOX, and suggest that these effects were correlated with the
      prevention of the overexpression of Nrf2 and its target proteins, which occurred
      in the cells submitted to drug treatment.

PMID- 29354294
TI  - An Introduction to Principal Surrogate Evaluation with the pseval Package.
AB  - We describe a new package called pseval that implements the core methods for the
      evaluation of principal surrogates in a single clinical trial. It provides a
      flexible interface for defining models for the risk given treatment and the
      surrogate, the models for integration over the missing counterfactual surrogate
      responses, and the estimation methods. Estimated maximum likelihood and pseudo
      score can be used for estimation, and the bootstrap for inference. A variety of
      post-estimation methods are provided, including print, summary, plot, and
      testing. We summarize the main statistical methods that are implemented in the
      package and illustrate its use from the perspective of a novice R user.

PMID- 29354293
TI  - Bi-valent polysaccharides of Vi capsular and O9 O-antigen in attenuated
      Salmonella Typhimurium induce strong immune responses against these two antigens.
AB  - Salmonella Typhi is the causative agent of typhoid fever in humans, responsible
      for approximately 21 million infections and 222,000 deaths globally each year.
      The current licensed vaccines provide moderate protection to recipients aged >2
      years. Prior work on typhoid vaccines has focused on injectable Vi capsular
      polysaccharide or Vi-protein conjugates and live, oral attenuated S. Typhi
      vaccines to induce humoral anti-Vi antibodies, while the value and importance of
      anti-O9 antibodies is less well established. In this study, we constructed a S.
      Typhimurium strain that synthesizes Vi capsular antigen in vivo and produces the
      immunodominant O9-antigen polysaccharide instead of its native O4-antigen. The
      live recombinant attenuated S. Typhimurium mutants were effective in stimulating
      anti-Vi and anti-O9 antibodies in a mouse model, and the surface Vi capsular
      expression did not affect the immune responses against the O9 O-antigen
      polysaccharide. Moreover, the resulting anti-Vi and anti-O9 antibodies were
      effective at killing S. Typhi and other Salmonella spp. expressing Vi or O9
      antigen polysaccharides and provided efficient protection against lethal
      challenge by S. Typhimurium and S. Enteritidis. Our work highlights the strategy
      of developing live attenuated S. Typhimurium vaccines to prevent typhoid fever by
      targeting the both Vi capsular and O9 O-polysaccharide antigens simultaneously.

PMID- 29354295
TI  - Morphological classification and comparison of suboccipital muscle fiber
      characteristics.
AB  - In an attempt to clarify the function of the suboccipital muscles, we performed
      morphological observation of the suboccipital muscles for variations in the
      muscle belly and compared the morphology of their muscle fibers in terms of cross
      sectional area by immunostaining with anti-myosin heavy chain antibodies. The
      cadavers of 25 Japanese individuals were used: 22 for morphological examinations
      and three for histological examinations. Among samples of the rectus capitis
      posterior major muscle (RCPma) and rectus capitis posterior minor muscle (RCPmi),
      86.4% had a typical muscle appearance with a single belly, and 13.6% had an
      anomalous morphology. None of the samples of the obliquus capitis superior (OCS)
      or obliquus capitis inferior (OCI) muscles had an anomalous appearance.
      Measurement of cross-sectional area revealed that fast-twitch muscle fibers in
      the RCPma and OCI had a significantly greater cross-sectional area than those of
      the RCPmi and OCS. The cross-sectional area of intermediate muscle fibers was
      also significantly greater in the OCS than in the RCPma, RCPmi, and OCI. The
      cross-sectional area of slow-twitch muscle fibers was significantly greater in
      the OCS than in the RCPma, RCPmi, and OCI, and the RCPmi showed a significantly
      greater cross-sectional area for slow-twitch muscle fibers than did the RCPma,
      and OCI. Our findings indicate that the RCPmi and OCS exert a greater force than
      the RCPma and OCI, and act as anti-gravity agonist muscles of the head. Prolonged
      head extension in individuals with anomalous suboccipital muscle groups could
      result in dysfunction due to undue stress.

PMID- 29354297
TI  - A new method for sex estimation from maxillary suture length in a Thai
      population.
AB  - Sex estimation is one of the crucial procedures in the biological profile
      identification of human skeletal remains. Knowing sex of unknown case can lead to
      accurate and appropriate methods for predicting age, stature, ancestry, or even
      personal identification. Skull is one of the most reliable one among other
      skeletons and it is usually retained for both archaeological and forensic
      contexts. Although many morphological features and metric measurements of skull
      have been studied for sexing, but to the best of our knowledge is no study on
      maxillary suture length for sex estimation. Therefore, this study aims to develop
      a new sex estimation method for a Thai population by determining three maxillary
      suture lengths: anterior, transverse, and posterior maxillary suture, by
      computerizing amount of pixel obtained from photographs of these sutures. The
      present study was conducted on 190 Thai bone samples of which 96 were males and
      94 were females. Independent t test revealed statistically significant difference
      (P<0.01) between males and females in all maxillary suture measurements.
      Equations derived from prediction model, which required three maxillary suture
      lengths gave 76.8421% accuracy from the leave-one-out cross validation in
      estimating sex percentage accuracies in predicting sex from these equations,
      which were relatively moderate. This study provides a novel and objective sex
      estimation method for Thais. It suggests that maxillary suture length can be
      applied for sex estimation. The new computerized technique will contribute basis
      knowledge and method for sex estimation, especially when only base of skull is
      available in forensic circumstance.

PMID- 29354296
TI  - Learning styles and strategies preferences of Iranian medical students in gross
      anatomy courses and their correlations with gender.
AB  - The learning approaches can help anatomy teachers design a suitable curriculum in
      harmony with their students' learning styles. The research objective is to
      evaluate gross anatomy learning styles and strategies preferences of Iranian
      medical students at Kashan University of Medical Sciences (KAUMS). This cross
      sectional questionnaire-based study was carried out on 237 Iranian medical
      students. The students answered questions on approaches to learning anatomy and
      expressed opinions about learning anatomy in medical curriculum. The data were
      analyzed to disclose statistically significant differences between male and
      female students. Iranian male and female students were interested in learning
      anatomy using notes, plastic models, pictures and diagrams, clinical context,
      dissection and prosection of cadavers; however, they rarely used cross-sectional
      images and web-based resources. Both groups of medical students used region and
      system in learning anatomy. However, there existed some striking differences,
      particularly in having difficulty in studying anatomy using cadaveric specimens,
      using books alone, and learning it in small groups. Male students were less
      interested in learning with cadavers than female counterparts. However, female
      students were more interested in learning anatomy in small groups. This study
      suggests that instructors should design gross anatomy curriculum based on
      limitations of using dissection of cadaver in Iranian universities, emphasis on
      the applied anatomy, and learning of gross anatomy in small groups.

PMID- 29354298
TI  - Age-related trends of lesser pelvic architecture in females and males: a computed
      tomography pelvimetry study.
AB  - The pelvis and the spine form a system balancing human skeleton. Within this
      system, the pelvis adapts to age-related changes in the spine. Previous studies
      were predominantly focused on changes of pelvic parameters in the sagittal plane.
      The aim of this study was to reveal age-related changes of lesser pelvic
      dimensions at different levels of the pelvic cavity in the sagittal and coronal
      planes and to explore sexual dimorphism in age-related tendencies. The computed
      tomography pelvimetry was performed on the three-dimensional workstation. The
      research sample included 211 females aged 18 to 84 years and 181 males aged 18 to
      82 years, who underwent an examination at the Riga East University Hospital,
      Clinical Center "Gailezers," Latvia. Three pelvic angles and transverse and
      sagittal diameters of the lesser pelvis were measured at four levels: the inlet,
      two axial planes in the mid-cavity, and the outlet. The results demonstrated that
      more pronounced age-related changes occurred in the inlet and the outlet of the
      lesser pelvis. The mid-cavity was less changing. The transverse diameter between
      acetabular centers and the sagittal diameter at the level of ischial spines were
      independent of age. In general, the common age-related trends were observed for
      pelvic parameters in females and males. A single exception was the proportion of
      diameters at the level of ischial spines, which decreased in males only. For
      parameters associated with pelvic floor diseases, age-related changes occurred in
      the direction of pathology.

PMID- 29354299
TI  - Ameliorative effects of type-A procyanidins polyphenols from cinnamon bark in
      compound 48/80-induced mast cell degranulation.
AB  - Allergic diseases are a significant health concern in developing countries. Type
      A procyanidin polyphenols from cinnamon (Cinnamomum zeylanicum Blume) bark (TAPP
      CZ) possesses antiasthmatic and antiallergic potential. The present study was
      aimed at the possible anti-allergic mechanism of TAPP-CZ against the compound
      48/80 (C48/80)-induced mast cell degranulation in isolated rat peritoneal mast
      cells (RPMCs). TAPP-CZ (1, 3, 10, and 30 ug/ml) was incubated for 3 hours with
      isolated, purified RPMCs. The C48/80 (1 ug/ml) was used to induce mast cell
      degranulation. The mast cell viability was assessed using 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay whereas histamine, beta
      hexosaminidase (beta-HEX), and interleukin-4 (IL-4) levels were determined in
      RPMCs. TAPP-CZ (3, 10, and 30 ug/ml) showed significant and dose-dependent
      decrease in a number of degranulated cells and levels of markers (histamine, beta
      HEX, and IL-4) as compared with C48/80 control. In conclusion, TAPP-CZ stabilizes
      mast cell and cause inhibition of the allergic markers such as histamine, IL-4,
      and beta-HEX in IgE-mediated manner. The present study supports mast cell
      stabilization as a possible mechanism of action of TAPP-CZ against immune
      respiratory disorders such as asthma and allergic rhinitis.

PMID- 29354300
TI  - Pre-treated Populus tomentiglandulosa extract inhibits neuronal loss and
      alleviates gliosis in the gerbil hippocampal CA1 area induced by transient global
      cerebral ischemia.
AB  - The genus Populus (poplar) belonging to the Salicaceae family has been used in
      traditional medicine, and its several species show various pharmacological
      properties including antioxidant and anti-inflammatory effects. No study
      regarding protective effects of Populus species against cerebral ischemia has
      been reported. Therefore, in the present study, we examined neuroprotective
      effects of ethanol extract from Populus tomentiglandulosa (Korea poplar) in the
      hippocampal cornu ammonis (CA1) area of gerbils subjected to 5 minutes of
      transient global cerebral ischemia. Pretreatment with 200 mg/kg of P.
      tomentiglandulosa extract effectively protected CA1 pyramidal neurons from
      transient global cerebral ischemia. In addition, glial fibrillary acidic protein
      immunoreactive astrocytes and ionized calcium binding adapter molecule 1
      immunoreactive microglia were significantly diminished in the ischemic CA1 area
      by pretreatment with 200 mg/kg of P. tomentiglandulosa extract. Briefly, our
      results indicate that pretreatment with P. tomentiglandulosa extract protects
      neurons from transient cerebral ischemic injury and diminish cerebral ischemia
      induced reactive gliosis in ischemic CA1 area. Based on these results, we suggest
      that P. tomentiglandulosa can be used as a potential candidate for prevention of
      ischemic injury.

PMID- 29354302
TI  - Application of stereological methods for unbiased estimation of sperm morphology
      in the mice induced by busulfan.
AB  - Busulfan is an anticancer drug, which causes the apoptosis germ cells and
      azoospermia in humans and animals. Abnormal morphology of spermatozoa related to
      the male infertility. The sperm morphology is evaluation of sperm size, shape and
      appearance characteristics should be assessed by carefully observing a stained
      sperm sample under the microscope. Evaluation of sperm morphology has been
      considered as one of the most important factors for a successful fertilization
      and determining sperm quality. The mice were assigned to tow experimental groups:
      control and busulfan. Each group included six mice that were housed under
      standard conditions. The volume was estimated using the nucleator method. The
      sperm's flegellum and mid-piece length was estimated by counting the number of
      intersections between the tails and Merz grid test line in an unbiased counting
      frame, superimposed on live images of sperms. Our results demonstrated a
      significant different in the volume and surface of the sperm's head and the
      length of the sperm's flagellum in the control and busulfan groups. Busulfan can
      effect on the volume of the sperm's head and the length of the sperm's flagellum
      in rat.

PMID- 29354301
TI  - Celecoxib induces cell death on non-small cell lung cancer cells through
      endoplasmic reticulum stress.
AB  - Cyclooxygenase-2 (COX-2) is an enzyme induced by various proinflammatory and
      mitogenic stimuli. Celecoxib is a selective inhibitor of COX-2 that have been
      shown to affect cell growth and apoptosis. Lung cancer cells expressing COX-2 is
      able to be a target of celecoxib, this study focuses on investigating that
      celecoxib induces apoptosis via endoplasmic reticulum (ER) stress on lung cancer
      cells. We investigated whether celecoxib induced apoptosis on non-small cell lung
      cancer cell line, A549 and H460. The 50 uM of celecoxib increased apoptotic cells
      and 100 uM of celecoxib significantly induced apoptosis. To check involvement of
      caspase cascade, pretreatment of z-VAD-fmk blocked celecoxib-induced apoptosis.
      However, caspase-3, -8, and -9 were not activated, but cleavage of non-classical
      caspase-4 was detected using western blot. As checking ER stress associated
      molecules, celecoxib did not increase expressions of growth arrest and DNA damage
      inducible protein 34, activating transcription factor 4, and spliced X-box
      binding protiens-1, but increase of both glucose-regulated protein 78 (GRP78) and
      C/EBP homologous transcription factor were detected. Salubrinal, inhibitor of
      eIF2 and siRNA for IRE1 did not alter celecoxib-induced apoptosis. Instead,
      celecoxib-induced apoptosis might be deeply associated with ER stress depending
      on GRP78 because siRNA for GRP78 enhanced apoptosis. Taken together, celecoxib
      triggered ER stress on lung cancer cells and celecoxib-induced apoptosis might be
      involved in both non-classical caspase-4 and GRP78.

PMID- 29354303
TI  - The presence of sharp-edged weapon related cut mark in Joseon skull discovered at
      the 16th century market district of Old Seoul City ruins in South Korea.
AB  - A human skull was discovered at the 16th-century drainage channel of market
      district ruins, one of the busiest streets in the capital of Joseon kingdom. By
      anthropological examination, we noticed the cut mark at the right occipital part
      of the cranium. Judging from the wound property, it might have been caused by a
      strong strike using a sharp-edged weapon. As no periosteal reaction or healing
      signs were observed at the cut mark, he might have died shortly after the skull
      wound was made. We speculated that this might have been of a civilian or soldier
      victim who died in a battle or the decapitated head of prisoner. This is the
      first report about the discovery of the skull damaged by sharp-edged weapon at
      the archaeological sites in the capital city of Joseon Kingdom.

PMID- 29354305
TI  - Some historical musings on tooth/root resorption.
AB  - Contemporarily, the ravages of tooth resorption are seen daily around the world.
      While some teeth can be retained many are lost to this process. Although many
      types of resorptive processes have been identified, the etiological factors
      involved in this malady are not often clear and both speculation as to it source
      and clinical management have received a great deal of empirical explanations and
      directives, respectively. However, this was not always the case, as the nature of
      tooth resorption, as is known today, was not really addressed in a significant
      manner until the mid-1970s. In fact, when first identified as a problem in the
      early 1800s, the term resorption did not even exist and the process was poorly
      understood. This historical review of tooth resorption will trace the evolution
      of some of our ideas about this malady, identifying both the concepts and
      personalities involved in this evolution.

PMID- 29354306
TI  - Odontogenic tumors: where are we in 2017 ?
AB  - Odontogenic tumors are a heterogeneous group of lesions of diverse clinical
      behavior and histopathologic types, ranging from hamartomatous lesions to
      malignancy. Because odontogenic tumors arise from the tissues which make our
      teeth, they are unique to the jaws, and by extension almost unique to dentistry.
      Odontogenic tumors, as in normal odontogenesis, are capable of inductive
      interactions between odontogenic ectomesenchyme and epithelium, and the
      classification of odontogenic tumors is essentially based on this interaction.
      The last update of these tumors was published in early 2017. According to this
      classification, benign odontogenic tumors are classified as follows: Epithelial,
      mesenchymal (ectomesenchymal), or mixed depending on which component of the tooth
      germ gives rise to the neoplasm. Malignant odontogenic tumors are quite rare and
      named similarly according to whether the epithelial or mesenchymal or both
      components is malignant. The goal of this review is to discuss the updated
      changes to odontogenic tumors and to review the more common types with clinical
      and radiological illustrations.

PMID- 29354304
TI  - Calcium phosphate cements for bone engineering and their biological properties.
AB  - Calcium phosphate cements (CPCs) are frequently used to repair bone defects.
      Since their discovery in the 1980s, extensive research has been conducted to
      improve their properties, and emerging evidence supports their increased
      application in bone tissue engineering. Much effort has been made to enhance the
      biological performance of CPCs, including their biocompatibility,
      osteoconductivity, osteoinductivity, biodegradability, bioactivity, and
      interactions with cells. This review article focuses on the major recent
      developments in CPCs, including 3D printing, injectability, stem cell delivery,
      growth factor and drug delivery, and pre-vascularization of CPC scaffolds via co
      culture and tri-culture techniques to enhance angiogenesis and osteogenesis.

PMID- 29354307
TI  - Alloplastic reconstruction of the temporomandibular joint.
AB  - Temporomandibular joint reconstruction (TMJR) is often necessary for patients
      with severe and/or refractory TMJ disease who have failed conservative treatment.
      TMJR aids to improve masticatory function and is associated with improved quality
      of life outcomes. Currently, alloplastic reconstruction is considered as the
      treatment of choice in most severe TMJ disorders due to its many advantages
      inclusive but not limited to early mobilization, stable longterm results, and
      significant improvement in jaw function. Broadly speaking, two types of TMJR
      prostheses are available for reconstruction: 1) stock, and, 2) custommade
      prostheses. The purpose of this article is to provide the reader with a brief
      overview of the basic principles and fundamentals of TMJR while referencing
      pertinent existing literature.

PMID- 29354308
TI  - A review of regenerative endodontics: current protocols and future directions.
AB  - This review outlines the biological basis and clinical protocols currently used
      in regenerative endodontic procedures (REPs) and discuss future directions in
      pulp regeneration approaches. The treatment of immature teeth with REPs has been
      described as a 'paradigm shift' as there is the potential for further root
      maturation. Clinically, REPs involve disinfection of the root canal system
      without damaging the endogenous stem cell potential present in the apical papilla
      and other tissues. These stems cells are introduced into the root canal space by
      inducing a blood clot followed by placement of an intracanal barrier to prevent
      microleakage. The biological concept of REPs involves the triad of stem cells,
      scaffold and signalling molecules. Currently, repair rather than true
      regeneration of the 'pulp-dentine complex' is achieved and further root
      maturation is variable. However, may clinicians consider the treatment of teeth
      with REPs as the optimal treatment approach for immature teeth with pulp
      necrosis.

PMID- 29354309
TI  - Review of nasal changes with maxillary orthognathic surgery.
AB  - This article reviews the literature on nasal changes with maxillary orthognathic
      surgery. Understanding such changes is vital for surgical planning and for
      obtaining appropriate informed consent, and there are medico-legal implications.
      During orthognathic surgical planning a prediction of the effects of the
      different surgical movements is possible and this forms part of the basis of the
      planning stage. The predicted changes need to be identified and their
      desirability or not for each individual patient determined. Some techniques for
      managing undesirable nasal changes are discussed, including adjunct measures to
      minimize these potential effects (e.g. cinch sutures), and additional surgical
      procedures to manage the undesired nasal changes once they are produced.

PMID- 29354310
TI  - Imaging evaluation of trigeminal neuralgia.
AB  - Trigeminal neuralgia is a debilitating pain syndrome in the sensory distribution
      of the trigeminal nerve. Compression of the cisternal segment of the trigeminal
      nerve by a vessel, usually an artery, is considered the most common cause of
      trigeminal neuralgia. A number of additional lesions may affect the trigeminal
      nerve anywhere along its course from the trigeminal nuclei to the most peripheral
      branches to cause facial pain. Relevant differential considerations are reviewed
      starting proximally at the level of the brainstem.

PMID- 29354311
TI  - Dental splints: types and time of immobilization post tooth avulsion.
AB  - Avulsion is defined as the complete displacement of the tooth out of its socket
      with disruption of the fibers of periodontal ligament, remaining some of them
      adhered to the cementum and the rest to the alveolar bone. This condition is more
      frequent in young permanent teeth, because the root development is still
      incomplete. Splints are used to immobilize traumatized teeth that suffered damage
      in their structures of support, preventing their constant movement. The
      literature has shown that after replantation, it is necessary to use splints in
      order to immobilize the teeth during the initial period, which is essential for
      the repair of periodontal ligament; the use of semi-rigid splint is more
      indicated than the rigid one, and long periods of splinting showed that
      substitutive resorption or ankylosis is an expected complication. Thus, the aim
      of this review is to describe the different types of splints; their time of
      permanency, and its influence on the process of healing and reparation on the
      occurrence of substitutive resorption or ankylosis. It is very important to keep
      gathering knowledge about this content, since it has been proved that the
      approaches and the protocols keep changing over time.

PMID- 29354312
TI  - Advanced dental implant placement techniques.
AB  - The availability of in office Cone Beam CT (CBCT) scanners, dental implant
      planning software, CAD CAM milling, and rapid printing technologies allow for the
      precise placement of dental implants and immediate prosthetic temporization.
      These technologies allow for flapless implant placement, or open flap bone
      reduction for "All on 4" techniques with improved preoperative planning and
      intraoperative performance. CBCT permits practitioners in an office setting with
      powerful diagnostic capabilities for the evaluation of bone quality and quantity,
      as well as dental and osseous pathology essential for better informed dental
      implant treatment. CBCT provides the convenience of in office imaging and
      decreased radiation exposure. Rapid printing technologies provide decreased time
      and high accuracy for bone model and surgical guide fabrication.

PMID- 29354313
TI  - Maxillary incisors changes during space closure with conventional and skeletal
      anchorage methods: a systematic review.
AB  - Purpose: The objective of this systematic review was to compare the antero
      posterior, vertical and angular changes of maxillary incisors with conventional
      anchorage control techniques and mini-implant based space closure methods.
      Materials and Methods: The electronic databases Pubmed, Scopus, ISI Web of
      knowledge, Cochrane Library and Open Grey were searched for potentially eligible
      studies using a set of predetermined keywords. Full texts meeting the inclusion
      criteria as well as their references were manually searched. The primary outcome
      data (linear, angular, and vertical maxillary incisor changes) and secondary
      outcome data (overbite changes, soft tissue changes, biomechanical factors, root
      resorption and treatment duration) were extracted from the selected articles and
      entered into spreadsheets based on the type of anchorage used. The methodological
      quality of each study was assessed. Results: Six studies met the inclusion
      criteria. The amount of incisor retraction was greater with buccally placed mini
      implants than conventional anchorage techniques. The incisor retraction with
      indirect anchorage from palatal mini-implants was less when compared with
      buccally placed mini-implants. Incisor intrusion occurred with buccal mini
      implants, whereas extrusion was seen with conventional anchorage. Limited data on
      the biomechanical variables or adverse effects such as root resorption were
      reported in these studies. Conclusion: More RCT's that take in to account
      relevant biomechanical variables and employ three-dimensional quantification of
      tooth movements are required to provide information on incisor changes during
      space closure.

PMID- 29354314
TI  - Cone beam computed tomography: basics and applications in dentistry.
AB  - The introduction of cone beam computed tomography (CBCT) devices, changed the way
      oral and maxillofacial radiology is practiced. CBCT was embraced into the dental
      settings very rapidly due to its compact size, low cost, low ionizing radiation
      exposure when compared to medical computed tomography. Alike medical CT, 3
      dimensional evaluation of the maxillofacial region with minimal distortion is
      offered by the CBCT. This article provides an overview of basics of CBCT
      technology and reviews the specific application of CBCT technology to oral and
      maxillofacial region with few illustrations.

PMID- 29354315
TI  - Thermo-cured glass ionomer cements in restorative dentistry.
AB  - Numerous positive properties of glass ionomer cements including biocompatibility,
      bioactivity, releasing of fluoride and good adhesion to hard dental tissue even
      under wet conditions and easy of handling are reasons for their wide use in
      paediatric and restorative dentistry. Their biggest drawbacks are the weaker
      mechanical properties. An important step forward in improving GIC's features is
      thermo-curing with the dental polymerization unit during setting of the material.
      Due to their slow setting characteristics the GIC is vulnerable to early exposure
      to moisture. After thermo curing, cements retain all the benefits of GIC with
      developed better mechanical properties, improved marginal adaptation, increased
      microhardness and shear bond strength. Adding external energy through
      thermocuring or ultrasound during the setting of conventional GIC is crucial to
      achieve faster and better initial mechanical properties. Further clinical studies
      are needed to confirm these findings.

PMID- 29354316
TI  - Bioceramics in endodontics - a review.
AB  - Bioceramics are materials which include Alumina, Zirconia, Bioactive glass, Glass
      ceramics, Hydroxyapatite, resorbable Calcium phosphates, among others. They have
      been used in dentistry for filling up bony defects, root repair materials, apical
      fill materials, perforation sealing, as endodontic sealers and as aids in
      regeneration. They have certain advantages like biocompatibility, non toxicity,
      dimensional stability and most importantly in endodontic applications, being bio
      inert. They have a similarity to Hydroxyapatite, an intrinsic osteo conductive
      activity and have an ability to induce regenerative responses in the human body.
      In Endodontics, they can be broadly classified into Calcium Phosphate/
      Tricalcium/ Hydroxyapatite based, Calcium Silicate based or mixtures of Calcium
      Silicate and Phosphates. This review focuses on an overview of Bioceramics,
      classification and their advantages. It also gives a detailed insight into
      individual bioceramic materials currently used in the fields of Endodontics along
      with their properties and applications.

PMID- 29354317
TI  - Aminomethylation of Aryl Halides using alpha-Silylamines Enabled by Ni/Photoredox
      Dual Catalysis.
AB  - A protocol for the aminomethylation of aryl halides using alpha-silylamines via
      Ni/photoredox dual catalysis is described. The low oxidation potential of these
      silylated species enables facile single electron transfer (SET) oxidation of the
      amine followed by rapid desilylation. The resulting alpha-amino radicals can be
      directly funneled into a nickel-mediated cross-coupling cycle with aryl halides.
      The process accomplishes aminomethylation under remarkably mild conditions and
      tolerates numerous aryl- and heteroaryl halides with an array of functional
      groups.

PMID- 29354318
TI  - Promoting Regulatory Reform: The African Health Profession Regulatory
      Collaborative (ARC) for Nursing and Midwifery Year 4 Evaluation.
AB  - As countries across sub-Saharan Africa work towards universal health coverage and
      HIV epidemic control, investments seek to bolster the quality and relevance of
      the health workforce. The African Health Profession Regulatory Collaborative
      (ARC) partnered with 17 countries across East, Central, and Southern Africa to
      ensure nurses and midwives were authorized and equipped to provide essential HIV
      services to pregnant women and children with HIV. Through ARC, nursing leadership
      teams representing each country identify a priority regulatory function and
      develop a proposal to strengthen that regulation over a 1-year period. Each year
      culminates with a summative congress meeting, involving all ARC countries, where
      teams present their projects and share lessons learned with their colleagues.
      During a recent ARC Summative Congress, a group survey was administered to 11
      country teams that received ARC Year 4 grants to measure advancements in
      regulatory function using the five-stage Regulatory Function Framework, and a
      group questionnaire was administered to 16 country teams to measure improvements
      in national nursing capacity (February 2011-2016). In ARC Year 4, eight countries
      implemented continuing professional development projects, Botswana revised their
      scope of practice, Mozambique piloted a licensing examination to assess HIV
      related competencies, and South Africa developed accreditation standards for
      HIV/tuberculosis specialty nurses. Countries reported improvements in national
      nursing leaders' teamwork, collaborations with national organizations, regional
      networking with nursing leaders, and the ability to garner additional resources.
      ARC provides an effective, collaborative model to rapidly strengthen national
      regulatory frameworks, which other health professional cadres or regions may
      consider using to ensure a relevant health workforce, authorized and equipped to
      meet the emerging demand for health services.

PMID- 29354319
TI  - Dopaminergic enhancement of cellular adhesion in bone marrow derived mesenchymal
      stem cells (MSCs).
AB  - Dopamine (DA) is a well-known neurotransmitter and critical element in the mussel
      adhesive protein that has gained increasing attention for its role in cellular
      growth enhancement in biomaterials, including cellular adhesion improvement. As
      the mechanism underlying this remains unclear, the objective of this study was to
      explore the effects of DA on the adhesion properties of bone marrow derived rat
      mesenchymal stem cells (rMSCs) using an hydroxyapatite gelatin nanocomposite
      biomaterial and to test whether the effects are mediated through various
      endogenously expressed DA receptors. Primary rMSCs were pretreated with D1-like
      antagonist, D2-like antagonist, or a combination of these antagonists followed by
      treatment with 50 MUM DA and cellular adhesion quantification at 0.5, 1, 2 and 4
      hours post DA addition. DA was found to increase rMSC adhesion and spreading at
      the 0.5 hour time-point and the dopaminergic effect on cell adhesion was
      partially blocked by DA antagonists. In addition, the D1-like and D2-like
      antagonists appeared to have a similar effect on rMSCs. Immunofluorescent
      staining indicated that the rMSC spreading area was significantly increased in
      the DA treated group versus the control group. Treatment of the D1-like DA
      antagonists with DA revealed that the actin filaments of rMSCs could not connect
      the membrane with the nucleus. In summary, DA was found to enhance early rMSC
      adhesion partially via DA receptor activation.

PMID- 29354320
TI  - Simply derived epicardial cells.
AB  - A chemically defined protocol requiring no animal-derived components allows for
      the easier derivation and enduring expansion of epicardial cells from human
      pluripotent stem cells.

PMID- 29354321
TI  - A Fully Functional Drug-Eluting Joint Implant.
AB  - Despite advances in orthopedic materials, the development of drug-eluting bone
      and joint implants that can sustain the delivery of the drug and maintain the
      necessary mechanical strength in order to withstand loading has remained elusive.
      Here, we demonstrate that modifying the eccentricity of drug clusters and the
      percolation threshold in ultrahigh molecular weight polyethylene (UHMWPE) results
      in maximized drug elution and in the retention of mechanical strength. The
      optimized UHMWPE eluted antibiotic at a higher concentration for longer than the
      clinical gold standard antibiotic-eluting bone cement while retaining the
      mechanical and wear properties of clinically used UHMWPE joint prostheses.
      Treatment of lapine knees infected with Staphylococcus aureus with the antibiotic
      eluting UHMWPE led to complete bacterial eradication and to the absence of
      detectable systemic effects. We argue that the antibiotic-eluting UHMWPE joint
      implant is a promising candidate for clinical trials.

PMID- 29354323
TI  - Systemic Inflammation in C57BL/6J Mice Receiving Dietary Aluminum Sulfate; Up
      Regulation of the Pro-Inflammatory Cytokines IL-6 and TNFalpha, C-Reactive
      Protein (CRP) and miRNA-146a in Blood Serum.
AB  - A number of experimental investigations utilizing different murine species have
      previously reported: (i) that standard mouse-diets supplemented with
      physiologically realistic amounts of neurotoxic metal salts substantially induce
      pro-inflammatory signaling in a number of murine tissues; (ii) that these diet
      stimulated changes may contribute to a systemic inflammation (SI), a potential
      precursor to neurodegenerative events in both the central and the peripheral
      nervous system (CNS, PNS); and (iii) that these events may ultimately contribute
      to a chronic and progressive inflammatory neurodegeneration, such as that which
      is observed in Alzheimer's disease (AD) brain. In these experiments we assayed
      for markers of SI in the blood serum of C57BL/6J mice after 0, 1, 3 and 5 months
      of exposure to a standard mouse diet that included aluminum-sulfate in the food
      and drinking water, compared to age-matched controls receiving magnesium-sulfate
      or no additions. The data indicate that the SI markers that include the pro
      inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha
      (TNFalpha), the acute phase reactive protein C-reactive protein (CRP) production
      and a triad of pro-inflammatory microRNAs (miRNA-9, miRNA-125b and miRNA-146a)
      all increase in the serum after aluminum-sulfate exposure. For the first time
      these results suggest that ad libitum exposure to aluminum-sulfate at
      physiologically realistic concentrations, as would be found in the human diet
      over the long term, may predispose to SI and the potential development of
      chronic, progressive, inflammatory neurodegeneration with downstream pathogenic
      consequences.

PMID- 29354322
TI  - Local and sustained miRNA delivery from an injectable hydrogel promotes
      cardiomyocyte proliferation and functional regeneration after ischemic injury.
AB  - MicroRNA-based therapies that target cardiomyocyte proliferation have great
      potential for the treatment of myocardial infarction (MI). In previous work, we
      showed that the miR-302/367 cluster regulates cardiomyocyte proliferation in the
      prenatal and postnatal heart. Here, we describe the development and application
      of an injectable hyaluronic acid (HA) hydrogel for the local and sustained
      delivery of miR-302 mimics to the heart. We show that the miR-302 mimics released
      in vitro promoted cardiomyocyte proliferation over one week, and that a single
      injection of the hydrogel in the mouse heart led to local and sustained
      cardiomyocyte proliferation for two weeks. After MI, gel/miR-302 injection caused
      local clonal proliferation and increased cardiomyocyte numbers in the border zone
      of a Confetti mouse model. Gel/miR-302 further decreased cardiac end-diastolic
      (39%) and end-systolic (50%) volumes, and improved ejection fraction (32%) and
      fractional shortening (64%) four weeks after MI and injection, compared to
      controls. Our findings suggest that biomaterial-based miRNA delivery systems can
      lead to improved outcomes in cardiac regeneration.

PMID- 29354324
TI  - Comparison of Patient Outcome Measures between a Traditional Teaching Hospitalist
      Service and a Non-Teaching Hospitalist Service at an Academic Children's
      Hospital.
AB  - Background and objectives: Inpatient pediatric care is increasingly provided by
      pediatric hospitalists. This, in addition to changes in resident duty hour
      restrictions, has led to the creation of new models of care for inpatient
      pediatric patients. The objective of this study was to compare traditional
      outcome measures between a pediatric hospitalist-only service and a more
      traditional academic service in which care was provided by pediatric
      hospitalists, residents, and medical students. Attending physicians on the
      hospitalist-only service had an average of 1.7 years of post-residency experience
      compared to an average 16 years of experience for those working on the
      traditional academic service. Methods: This retrospective cohort study
      (hospitalist-only v. teaching service) used electronic medical records data of
      patients (n=1,059) admitted to a quaternary care, academic, children's hospital
      in Pittsburgh Pennsylvania with diagnoses of bronchiolitis, viral syndrome, and
      gastroenteritis from July 2011 to June 2014. Primary outcome measures included
      length of stay, hospital costs, and readmission rates. Results: Patients with a
      diagnosis of bronchiolitis admitted to the hospitalist-only service had a
      significantly higher severity-of-illness-score than those admitted to the
      teaching service. A decreased length of stay and lower hospital costs were seen
      for patients admitted to the hospitalist-only service; however, these differences
      did not reach a level of statistical significance. Conclusion: There were no
      statistically significant differences in the outcome measures of patients with
      common pediatric illnesses admitted to a hospitalist-only versus a teaching
      hospitalist service. The model of a hospitalist-only service staffed by recent
      residency graduates may provide an efficient and effective model of care as
      patients admitted to this service had similar outcome measures to those patients
      cared for by more-experienced attending physicians.

PMID- 29354325
TI  - Community Identity and User Engagement in a Multi-Community Landscape.
AB  - A community's identity defines and shapes its internal dynamics. Our current
      understanding of this interplay is mostly limited to glimpses gathered from
      isolated studies of individual communities. In this work we provide a systematic
      exploration of the nature of this relation across a wide variety of online
      communities. To this end we introduce a quantitative, language-based typology
      reflecting two key aspects of a community's identity: how distinctive, and how
      temporally dynamic it is. By mapping almost 300 Reddit communities into the
      landscape induced by this typology, we reveal regularities in how patterns of
      user engagement vary with the characteristics of a community. Our results suggest
      that the way new and existing users engage with a community depends strongly and
      systematically on the nature of the collective identity it fosters, in ways that
      are highly consequential to community maintainers. For example, communities with
      distinctive and highly dynamic identities are more likely to retain their users.
      However, such niche communities also exhibit much larger acculturation gaps
      between existing users and newcomers, which potentially hinder the integration of
      the latter. More generally, our methodology reveals differences in how various
      social phenomena manifest across communities, and shows that structuring the
      multi-community landscape can lead to a better understanding of the systematic
      nature of this diversity.

PMID- 29354326
TI  - Loyalty in Online Communities.
AB  - Loyalty is an essential component of multi-community engagement. When users have
      the choice to engage with a variety of different communities, they often become
      loyal to just one, focusing on that community at the expense of others. However,
      it is unclear how loyalty is manifested in user behavior, or whether certain
      community characteristics encourage loyalty. In this paper we operationalize
      loyalty as a user-community relation: users loyal to a community consistently
      prefer it over all others; loyal communities retain their loyal users over time.
      By exploring a large set of Reddit communities, we reveal that loyalty is
      manifested in remarkably consistent behaviors. Loyal users employ language that
      signals collective identity and engage with more esoteric, less popular content,
      indicating that they may play a curational role in surfacing new material. Loyal
      communities have denser user-user interaction networks and lower rates of triadic
      closure, suggesting that community-level loyalty is associated with more cohesive
      interactions and less fragmentation into subgroups. We exploit these general
      patterns to predict future rates of loyalty. Our results show that a user's
      propensity to become loyal is apparent from their initial interactions with a
      community, suggesting that some users are intrinsically loyal from the very
      beginning.

PMID- 29354327
TI  - Understanding cancer-related fatigue: advancing the science.

PMID- 29354328
TI  - The Regulation of Notch Signaling in Retinal Development and Regeneration.
AB  - Purpose of review: Notch signaling is an important component of retinal
      progenitor cell maintenance and MG specification during development, and its
      manipulation may be critical for allowing MG to re-enter the cell cycle and
      regenerate neurons in adults. In mammals, MG respond to retinal injury by
      undergoing a gliotic response rather than a regenerative one. Understanding the
      complexities of Notch signaling may allow for strategies that enhance
      regeneration over gliosis. Recent findings: Notch signaling is regulated at
      multiple levels, and is interdependent with various other signaling pathways in
      both the receptor and ligand expressing cells. The precise spatial and temporal
      patterning of Notch components is necessary for proper retinal development.
      Regenerative species undergo a dynamic regulation of Notch signaling in MG upon
      injury, whereas non-regenerative species fail to productively regulate Notch.
      Summary: Notch signaling is malleable, such that the altered composition of
      growth and transcription factors in the developing and mature retinas result in
      different Notch mediated responses. Successful regeneration will require the
      manipulation of the retinal environment to foster a dynamic rather than static
      regulation of Notch signaling in concert with other reprogramming and
      differentiation factors.

PMID- 29354329
TI  - Negative Urgency Mediates the Relation between Genetically-Influenced Serotonin
      Functioning and Alcohol Problems.
AB  - Serotonin (5-HT) functioning is associated with alcohol problems. However, the
      mechanisms underlying this association remain unclear. The current study tested
      whether five separate dimensions of impulsivity (UPPS-P) mediated the relation
      between a polygenic score indexing 5-HT functioning and alcohol problems and
      whether any of these paths were moderated by age. Results showed that a 5-HT
      polygenic score predicted alcohol problems indirectly through negative urgency,
      but not any other facet of impulsivity. The 5-HT polygenic score also directly
      predicted alcohol problems. No age moderation was found. Findings suggest that
      negative urgency might be one important mechanism underlying the relation between
      genetically-influenced 5-HT functioning and alcohol problems. However,
      genetically-influenced 5-HT functioning likely influences alcohol problems
      through additional mechanisms. More broadly, results suggest that the previously
      observed transdiagnostic nature of 5-HT functioning on diverse types of
      psychopathology might be, in part, explained by its effect on negative urgency.

PMID- 29354330
TI  - Synthesis, Biological Evaluation and Modeling Studies of New Pyrido[3,4-b]indole
      Derivatives as Broad-Spectrum Potent Anticancer Agents.
AB  - Objective: There is an urgent need drugs against particularly difficult to treat
      solid tumors such as pancreatic, triple negative breast, lung, colon, metastatic
      prostate cancers and melanoma. Thus, the objective of this study was to
      synthesize compounds based computational modeling that indicated the pyrido[3,4
      b]indole class bind to MDM2, a new cancer target for which there are still no
      drug on the market. Methods: Compounds were synthesized by established methods
      and tested for antiproliferative activity against a broad range of human cancer
      cell lines, comprising HCT116 colon, HPAC, MIA PaCa-2 and Panc-1 pancreatic, MCF
      7 and MDA-MB-468 breast, A375 and WM164 melanoma, A549 lung, and LNCaP, DU145 and
      PC3 prostate cancer lines. Computational docking was also undertaken. Results:
      The novel pyrido[3,4-b]indoles synthesized exhibited a clear SAR with regards to
      antiproliferative activity, with potent broad-spectrum anticancer activity with
      IC50s down to 80, 130, 130 and 200 nM for breast, colon, melanoma and pancreatic
      cancer cells, respectively. 1-Naphthyl at C1 combined with methoxy at C6 provided
      the best antiproliferative activity. Thus, compound 11 (1-naphthyl-6-methoxy-9H
      pyrido[3,4-b]indole) showed the highest potency. A mechanistic feature of the
      compounds as a group is a strongly selective G2/M cell cycle phase arrest.
      Docking at on MDM2 suggested a hydrogen bond interaction between the 6-methoxy
      Tyr106, hydrophobic interaction with Val93, pi-pi stacking interactions with
      Tyr100 and His96 and hydrophobic interactions with Leu54 and Ile99. An N9-methyl
      group disrupted binding interactions, such as H-bond interactions involving the
      N9 hydrogen. Conclusion: We have identified a novel series of pyrido[3,4
      b]indoles with potent broad spectrum anticancer activity towards the most
      aggressive and difficult to treat cancers including metastatic pancreatic cancer,
      non-small cell lung cancer, triple negative breast cancers, and BRAFV600E mutant
      melanoma, as well as metastatic colon and prostate cancers. There was also
      evidence of selectivity towards cancer cells relative to normal cells. These
      compounds will serve as new leads from which novel therapeutics and molecular
      tools can be developed for a wide variety of cancers.

PMID- 29354331
TI  - Pazopanib-mediated Long-term Disease Stabilization after Local Recurrence and
      Distant Metastasis of Primary Intracranial Leiomyosarcoma: A Case Report on the
      Efficacy of Pazopanib as a Salvage Therapy.
AB  - Primary intracranial leiomyosarcoma (LMS) is an extremely rare tumor of the
      central nervous system. Only sporadic case reports have been published, and
      therefore data regarding long-term prognosis remain scarce. A 76-year-old woman
      presented with a right parietal mass, which had grown rapidly in the month prior
      to admission. Neuroimaging showed a resemblance to intraosseous meningioma. Gross
      total resection of the tumor was achieved, and histological diagnosis confirmed
      LMS. Because positron emission tomography (PET) with fluorodeoxyglucose (FDG)
      just after the resection showed no abnormal uptake, we diagnosed the tumor as
      primary intracranial LMS. Follow-up PET at 16 months after treatment showed two
      foci of FDG uptake in the bilateral lungs. Histological diagnosis by surgical
      resection identified the lesions as lung metastases of LMS. In addition, follow
      up head magnetic resonance imaging (MRI) at 31 months showed local recurrence,
      and we conducted salvage therapy using CyberKnife system (Accuray incorporated)
      and pazopanib. To date, for 15 months after local recurrence, she is alive with
      intracranial recurrent disease remained inactive.

PMID- 29354332
TI  - Tumor Volume Decrease via Feeder Occlusion for Treating a Large, Firm Trigone
      Meningioma.
AB  - Trigone meningiomas are considered a surgical challenge, as they tend to be
      considerably large and hypervascularized at the time of presentation. We
      experienced a case of a large and very hard trigone meningioma that was
      effectively treated using initial microsurgical feeder occlusion followed by
      surgery in stages. A 19-year-old woman who presented with loss of consciousness
      was referred to our hospital for surgical treatment of a brain tumor.
      Radiological findings were compatible with a left ventricular trigone meningioma
      extending laterally in proximity to the Sylvian fissure. At initial surgery using
      the transsylvian approach, main feeders originating from the anterior and lateral
      posterior choroidal arteries were occluded at the inferior horn; however, only a
      small section of the tumor could initially be removed because of its firmness.
      Over time, feeder occlusion resulted in tumor necrosis and a 20% decrease in its
      diameter; the mass effect was alleviated within 1 year. The residual meningioma
      was then totally excised in staged surgical procedures after resection became
      more feasible owing to ischemia-induced partial softening of the tumor. When a
      trigone meningioma is large and very hard, initial microsurgical feeder occlusion
      in the inferior horn can be a safe and effective option, and can lead to
      necrosis, volume decrease, and partial softening of the residual tumor to allow
      for its staged surgical excision.

PMID- 29354333
TI  - Transvenous Aneurysm Sac and Rupture Point Coil Embolization of Direct Carotid
      Cavernous Fistula after Pipeline Embolization.
AB  - A delayed aneurysm rupture after flow diverter therapy is a rare but serious
      complication. Due to the anatomical specificity, a delayed rupture of a carotid
      cavernous aneurysm may cause a direct carotid cavernous fistula (dCCF). We
      present a novel therapeutic approach for treatment of dCCF after flow diverter
      therapy using the Pipeline embolization device (PED). An 86-year-old woman
      suffered from dCCF after PED embolization. A microcatheter was advanced through
      the transvenous approach into the cavernous sinus (CS) and further inserted into
      the aneurysm sac via the rupture point. Coil embolization of both the aneurysm
      sac and a small part of the CS adjacent to the fistulous site could achieve not
      only the immediate aneurysm occlusion but also the rupture point obliteration
      with a small amount of coil mass in the CS.

PMID- 29354335
TI  - Adult Chiari Type 1 Malformation with Holocord Syringomyelia Associated with
      Sagittal Synostosis.
AB  - Craniosynostosis associated with Chiari malformation (CM) is usually found in
      infants with an underdeveloped posterior fossa. We here present a case of adult
      craniosynostosis, CM, and symptomatic syringomyelia caused by the protrusion of
      the posterior rim of the foramen magnum without a tight posterior fossa. A 22
      year-old woman with an abnormal head shape and forearm hypesthesia was given a
      diagnosis of sagittal suture synostosis with CM and syringomyelia caused by
      foramen magnum stenosis. She underwent foramen magnum decompression with a C1
      laminectomy without cranial vault expansion or duraplasty. Her symptoms and
      radiographical findings improved after surgery. In cases of non-operative
      craniosynostosis with CM, clinicians should be alert to late-onset syringomyelia
      and choose surgical strategies according to the pathophysiology.

PMID- 29354334
TI  - Traumatic Pseudoaneurysm of the Distal Anterior Cerebral Artery Following
      Penetrating Brain Injury Caused by a Crossbow Bolt: A Case Report.
AB  - Traumatic intracranial aneurysms are one possible complication after penetrating
      brain injury. A 25-year-old man with a history of major depression presented with
      a crossbow bolt penetrating the head. On arrival, Glasgow Coma Scale score was
      E4V5M6, with no apparent neurological deficit. Computed tomography (CT) of the
      head showed the crossbow bolt passing near the corpus callosum, with surrounding
      contusion. Three-dimensional rotational angiography showed no anterior cerebral
      artery injuries. The crossbow bolt was removed after bifrontal craniotomy, with
      no postoperative infection. Postoperative CT angiography (CTA) was repeatedly
      performed, and a 4 mm aneurysm was observed at the pericallosal artery-right
      posterior internal frontal artery (PIFA) bifurcation on postoperative day (POD)
      35. Trapping and the right PIFA-left cortical branch side-to-side bypass were
      performed on POD38. A resected specimen confirmed a pathological diagnosis of
      pseudoaneurysm. The patient did not show any neurological deficit or cognitive
      dysfunction as of 8 months after admission. Traumatic anterior cerebral artery
      aneurysm might have formed due to proximity to the falx cerebri. As
      pseudoaneurysm was detected 4 weeks after trauma in our patient, follow-up CTA or
      digital subtraction angiography should be performed until at least 4 weeks after
      injury. In addition, neck clipping is occasionally unfeasible to treat traumatic
      pseudoaneurysm surgically, and a surgical strategy including bypass
      revascularization must be planned.

PMID- 29354336
TI  - Severe Hypoglycemia-induced Right Hemiparesis with Reversible Diffusion
      Restriction in the Left Internal Capsule Due to Combination Therapy Using
      Disopyramide and Clarithromycin.
AB  - Severe hypoglycemia is known to cause acute focal neurological symptoms. In cases
      with a medical history of diabetes mellitus (DM), the diagnosis and treatment of
      hypoglycemia-induced neurological symptoms are simple. However, severe
      hypoglycemia can occur in patients who are not taking hypoglycemic agents such as
      insulin or long-acting sulfonylurea drugs. We describe a 95-year-old man with
      sudden onset of right hemiparesis who showed high signal intensity on diffusion
      weighted imaging involving the left internal capsule with corresponding reduced
      apparent diffusion coefficient hypointensity. Laboratory findings revealed severe
      hypoglycemia (27 mg/dl). However, he was not taking insulin or long-acting
      sulfonylurea drugs but disopyramide and clarithromycin had been administered. In
      addition, he had kidney dysfunction with an estimated glomerular filtration rate
      (GFR) of 42.9 ml/min/1.73 m2. After the blood glucose level was normalized, the
      left hemiparesis completely recovered and abnormal findings of magnetic resonance
      imaging (MRI) study also became normal. A combination of disopyramide and
      clarithromycin may cause severe hypoglycemia-induced neurological symptoms
      particularly in patients with kidney dysfunction. Even in a patient with sudden
      onset hemiparesis and no history of DM, the possibility of hypoglycemia-induced
      neurological deficit should be considered.

PMID- 29354337
TI  - Delayed Postoperative Spinal Epidural Hematoma after Cervical Laminoplasty.
AB  - A 56-year-old man underwent cervical laminoplasty for cervical spondylosis. On
      the 7th postoperative day, he suddenly felt severe neck pain, and tetraplegia
      developed rapidly over 1.5 hrs. Computed tomography demonstrated a huge hematoma
      compressing the cervical spinal cord. Clot was evacuated 3 hrs after the onset of
      symptoms. The patient's postoperative course was uneventful. His blood pressure
      could not be properly controlled in the perioperative period. Surgeons should
      keep in mind that delayed postoperative spinal epidural hematoma (DPSEH) can
      occur more than a week after surgery, and meticulous blood pressure control is
      important for more than a week after a spinal operation.

PMID- 29354338
TI  - Exploring wear at the nanoscale with circular mode atomic force microscopy.
AB  - The development of atomic force microscopy (AFM) has allowed wear mechanisms to
      be investigated at the nanometer scale by means of a single asperity contact
      generated by an AFM tip and an interacting surface. However, the low wear rate at
      the nanoscale and the thermal drift require fastidious quantitative measurements
      of the wear volume for determining wear laws. In this paper, we describe a new,
      effective, experimental methodology based on circular mode AFM, which generates
      high frequency, circular displacements of the contact. Under such conditions, the
      wear rate is significant and the drift of the piezoelectric actuator is limited.
      As a result, well-defined wear tracks are generated and an accurate computation
      of the wear volume is possible. Finally, we describe the advantages of this
      method and we report a relevant application example addressing a Cu/Al2O3
      nanocomposite material used in industrial applications.

PMID- 29354339
TI  - One-step chemical vapor deposition synthesis and supercapacitor performance of
      nitrogen-doped porous carbon-carbon nanotube hybrids.
AB  - Novel nitrogen-doped carbon hybrid materials consisting of multiwalled nanotubes
      and porous graphitic layers have been produced by chemical vapor deposition over
      magnesium-oxide-supported metal catalysts. CN x nanotubes were grown on Co/Mo,
      Ni/Mo, or Fe/Mo alloy nanoparticles, and MgO grains served as a template for the
      porous carbon. The simultaneous formation of morphologically different carbon
      structures was due to the slow activation of catalysts for the nanotube growth in
      a carbon-containing gas environment. An analysis of the obtained products by
      means of transmission electron microscopy, thermogravimetry and X-ray
      photoelectron spectroscopy methods revealed that the catalyst's composition
      influences the nanotube/porous carbon ratio and concentration of incorporated
      nitrogen. The hybrid materials were tested as electrodes in a 1M H2SO4
      electrolyte and the best performance was found for a nitrogen-enriched material
      produced using the Fe/Mo catalyst. From the electrochemical impedance
      spectroscopy data, it was concluded that the nitrogen doping reduces the
      resistance at the carbon surface/electrolyte interface and the nanotubes
      permeating the porous carbon provide fast charge transport in the cell.

PMID- 29354340
TI  - L-Lysine-grafted graphene oxide as an effective adsorbent for the removal of
      methylene blue and metal ions.
AB  - In this paper, novel L-lysine-modified graphene oxide (Lys-GO) was synthesized
      through amidation. The morphological and structural properties of Lys-GO were
      characterized using infrared spectrometry, scanning electronic microscopy and X
      ray photoelectron spectroscopy. The as-prepared Lys-GO material was
      systematically investigated in a series of batch adsorption experiments for the
      removal of methylene blue (MB) and copper ions (Cu2+) from wastewater. These
      results showed that Lys-GO is a bifunctional adsorbent for the removal of dyes
      and metal ions, and excellent adsorption efficiency was obtained. The maximum
      adsorption capacities for MB dye and Cu2+ were 1679.1 mg/g and 186.9 mg/g at 35 
      degrees C, respectively. The kinetics of adsorption followed well the linear
      pseudo-second-kinetic model. The isotherm results indicated that MB adsorption
      can be described with the Langmuir isotherm model, while the adsorption of Cu2+
      can be described with the Freundlich model. The excellent adsorption capacity
      indicated that the Lys-GO may be a promising adsorption material for the removal
      of environmental pollutants.

PMID- 29354341
TI  - Beyond Moore's technologies: operation principles of a superconductor
      alternative.
AB  - The predictions of Moore's law are considered by experts to be valid until 2020
      giving rise to "post-Moore's" technologies afterwards. Energy efficiency is one
      of the major challenges in high-performance computing that should be answered.
      Superconductor digital technology is a promising post-Moore's alternative for the
      development of supercomputers. In this paper, we consider operation principles of
      an energy-efficient superconductor logic and memory circuits with a short
      retrospective review of their evolution. We analyze their shortcomings in respect
      to computer circuits design. Possible ways of further research are outlined.

PMID- 29354342
TI  - Ab initio study of adsorption and diffusion of lithium on transition metal
      dichalcogenide monolayers.
AB  - Using first principles calculations, we studied the stability and electronic
      properties of transition metal dichalcogenide monolayers of the type MX2 (M = Ti,
      Zr, Hf, V, Nb, Ta, Mo, Cr, W; X= S, Se, Te). The adsorption and diffusion of
      lithium on the stable MX2 phase was also investigated for potential application
      as an anode for lithium ion batteries. Some of these compounds were found to be
      stable in the 2H phase and some are in the 1T or 1T' phase, but only a few of
      them were stable in both 2H/1T or 2H/1T' phases. The results show that lithium is
      energetically favourable for adsorption on MX2 monolayers, which can be
      semiconductors with a narrow bandgap and metallic materials. Lithium cannot be
      adsorbed onto 2H-WS2 and 2H-WSe2, which have large bandgaps of 1.66 and 1.96 eV,
      respectively. The diffusion energy barrier is in the range between 0.17 and 0.64
      eV for lithium on MX2 monolayers, while for most of the materials it was found to
      be around 0.25 eV. Therefore, this work illustrated that most of the MX2
      monolayers explored in this work can be used as promising anode materials for
      lithium ion batteries.

PMID- 29354343
TI  - Dry adhesives from carbon nanofibers grown in an open ethanol flame.
AB  - Based on magnetic-field-assisted growth of carbon nanofibers in an open ethanol
      flame we fabricated arrays of carbon nanofibers with different degrees of
      orientation. Inspired by the dry adhesive system of geckos we investigated the
      adhesive properties of such carbon nanofiber arrays with ordered and random
      orientation. AFM-based force spectroscopy revealed that adhesion force and energy
      rise linear with preload force. Carbon nanofibers oriented by a magnetic field
      show a 68% higher adhesion (0.66 N/cm2) than the randomly oriented fibers.
      Endurance tests revealed that the carbon nanofiber arrays withstand 50.000
      attachment/detachment cycles without observable wear.

PMID- 29354344
TI  - Hyperthermic intracavitary nanoaerosol therapy (HINAT) as an improved approach
      for pressurised intraperitoneal aerosol chemotherapy (PIPAC): Technical
      description, experimental validation and first proof of concept.
AB  - Background: The delivery of aerosolised chemotherapeutic substances into
      pressurised capnoperitonea has been reported to be more effective than
      conventional liquid chemotherapy for the treatment of peritoneal carcinomatosis.
      However, recent reports reveal limitations of the currently available technology.
      Material and Methods: A novel approach for pressurised intraperitoneal aerosol
      chemotherapy (PIPAC), called hyperthermic intracavitary nanoaerosol therapy
      (HINAT), based on extracavitary generation of hyperthermic and unipolar charged
      aerosols, was developed. The aerosol size distribution, the spatial drug
      distribution and in-tissue depth penetration of HINAT were studied by laser
      diffraction spectrometry, differential electrical mobility analysis, time of
      flight spectrometry, scintigraphic peritoneography and fluorescence microscopy.
      All experiments were performed contemporaneous with conventional PIPAC for the
      purpose of comparison. Furthermore, a first proof of concept was simulated in
      anesthetised German Landrace pigs. Results: HINAT provides a nanometre-sized (63
      nm) unipolar-charged hyperthermic (41  degrees C) drug aerosol for quasi uniform
      drug deposition over the whole peritoneum with significantly deeper drug
      penetration than that offered by conventional PIPAC.

PMID- 29354345
TI  - CdSe nanorod/TiO2 nanoparticle heterojunctions with enhanced solar- and visible
      light photocatalytic activity.
AB  - CdSe nanorods (NRs) with an average length of ~120 nm were prepared by a
      solvothermal process and associated to TiO2 nanoparticles (Aeroxide(r) P25) by
      annealing at 300  degrees C for 1 h. The content of CdSe NRs in CdSe/TiO2
      composites was varied from 0.5 to 5 wt %. The CdSe/TiO2 heterostructured
      materials were characterized by XRD, TEM, SEM, XPS, UV-visible spectroscopy and
      Raman spectroscopy. TEM images and XRD patterns show that CdSe NRs with wurtzite
      structure are associated to TiO2 particles. The UV-visible spectra demonstrate
      that the narrow bandgap of CdSe NRs serves to increase the photoresponse of
      CdSe/TiO2 composites until ~725 nm. The CdSe (2 wt %)/TiO2 composite exhibits the
      highest photocatalytic activity for the degradation of rhodamine B in aqueous
      solution under simulated sunlight or visible light irradiation. The enhancement
      in photocatalytic activity likely originates from CdSe sensitization of TiO2 and
      the heterojunction between these materials which facilitates electron transfer
      from CdSe to TiO2. Due to its high stability (up to ten reuses without any
      significant loss in activity), the CdSe/TiO2 heterostructured catalysts show high
      potential for real water decontamination.

PMID- 29354346
TI  - The rational design of a Au(I) precursor for focused electron beam induced
      deposition.
AB  - Au(I) complexes are studied as precursors for focused electron beam induced
      processing (FEBIP). FEBIP is an advanced direct-write technique for nanometer
      scale chemical synthesis. The stability and volatility of the complexes are
      characterized to design an improved precursor for pure Au deposition. Aurophilic
      interactions are found to play a key role. The short lifetime of ClAuCO in vacuum
      is explained by strong, destabilizing Au-Au interactions in the solid phase.
      While aurophilic interactions do not affect the stability of ClAuPMe3, they leave
      the complex non-volatile. Comparison of crystal structures of ClAuPMe3 and
      MeAuPMe3 shows that Au-Au interactions are much weaker or partially even absent
      for the latter structure. This explains its high volatility. However, MeAuPMe3
      dissociates unfavorably during FEBIP, making it an unsuitable precursor. The
      study shows that Me groups reduce aurophilic interactions, compared to Cl groups,
      which we attribute to electronic rather than steric effects. Therefore we propose
      MeAuCO as a potential FEBIP precursor. It is expected to have weak Au-Au
      interactions, making it volatile. It is stable enough to act as a volatile source
      for Au deposition, being stabilized by 6.5 kcal/mol. Finally, MeAuCO is likely to
      dissociate in a single step to pure Au.

PMID- 29354347
TI  - Impact of titanium dioxide nanoparticles on purification and contamination of
      nematic liquid crystals.
AB  - We have investigated the impact of titanium dioxide nanoparticles on the ionic
      contamination of liquid crystals. Nematic liquid crystals with high and low
      initial ionic contamination have been examined. It has been shown that titanium
      dioxide nanoparticles reduced the ion density of liquid crystals with high
      initial ionic contamination from 134.5 * 1012 cm-3 to 63.2 * 1012 cm-3. In the
      case of liquid crystals with low initial ionic contamination, the nanoparticles
      led to an insignificant increase of ion density from 19.8 * 1012 cm-3 to 25.7 *
      1012 cm-3.

PMID- 29354348
TI  - Material discrimination and mixture ratio estimation in nanocomposites via
      harmonic atomic force microscopy.
AB  - Harmonic atomic force microscopy (AFM) was employed to discriminate between
      different materials and to estimate the mixture ratio of the constituent
      components in nanocomposites. The major influencing factors, namely amplitude
      feedback set-point, drive frequency and laser spot position along the cantilever
      beam, were systematically investigated. Employing different set-points induces
      alternation of tip-sample interaction forces and thus different harmonic
      responses. The numerical simulations of the cantilever dynamics were well
      correlated with the experimental observations. Owing to the deviation of the
      drive frequency from the fundamental resonance, harmonic amplitude contrast
      reversal may occur. It was also found that the laser spot position affects the
      harmonic signal strengths as expected. Based on these investigations, harmonic
      AFM was employed to identify material components and estimate the mixture ratio
      in multicomponent materials. The composite samples are composed of different
      kinds of nanoparticles with almost the same shape and size. Higher harmonic
      imaging offers better information on the distribution and mixture of different
      nanoparticles as compared to other techniques, including topography and
      conventional tapping phase. Therefore, harmonic AFM has potential applications in
      various fields of nanoscience and nanotechnology.

PMID- 29354349
TI  - Facile synthesis of silver/silver thiocyanate (Ag@AgSCN) plasmonic nanostructures
      with enhanced photocatalytic performance.
AB  - A nanostructured plasmonic photocatalyst, silver/silver thiocyanate (Ag@AgSCN),
      has been prepared by a simple precipitation method followed by UV-light-induced
      reduction. The ratio of Ag to silver thiocyanate (AgSCN) can be controlled by
      simply adjusting the photo-induced reduction time. The formation mechanism of the
      product was investigated based on the time-dependent experiments. Further
      experiments indicated that the prepared Ag@AgSCN nanostructures with an atomic
      ratio of Ag/AgSCN = 0.0463 exhibited high photocatalytic activity and long-term
      stability for the degradation of oxytetracycline (84%) under visible-light
      irradiation. In addition to the microstructure and high specific surface area,
      the enhanced photocatalytic activity was mainly caused by the surface plasmon
      resonance of Ag nanoparticles, and the high stability of AgSCN resulted in the
      long-term stability of the photocatalyst product.

PMID- 29354350
TI  - Thermo- and electro-optical properties of photonic liquid crystal fibers doped
      with gold nanoparticles.
AB  - Thermo- and electro-optical properties of a photonic liquid crystal fiber (PLCF)
      enhanced by the use of dopants have been investigated. A 6CHBT nematic liquid
      crystal was doped with four different concentrations of gold nanoparticles (NPs),
      0.1, 0.3, 0.5 and 1.0 wt %, for direct comparison of the influence of the dopant
      on the properties of the PLCF. The thermo-optical effects of the liquid crystal
      doped with gold NPs were compared in three setups, an LC cell, a microcapillary
      and within the PLCF, to determine if the observed responses to external factors
      are caused by the properties of the infiltration material or due to the setup
      configuration. The results obtained indicated that with increasing NP doping a
      significant reduction of the rise time under an external electric field occurs
      with a simultaneous decrease in the nematic-isotropic phase transition
      temperature, thus improving the thermo- and electro-optical properties of the
      PLCF.

PMID- 29354351
TI  - Electro-optical characteristics of a liquid crystal cell with graphene
      electrodes.
AB  - In liquid crystal devices (LCDs) the indium tin oxide (ITO) films are
      traditionally used as transparent and conductive electrodes. However, today, due
      to the development of multichannel optical communication, the need for flexible
      LCDs and multilayer structures has grown. For this application ITO films cannot
      be used in principle. For this problem, graphene (an ultrathin material with
      unique properties, e.g., high optical transparency, chemical inertness, excellent
      conductivity) is an excellent candidate. In this work, the electro-optical and
      dynamic characteristics of a liquid crystal (LC) cell with graphene and ITO
      transparent conducting layers are investigated. To insure uniform thickness of
      the LC layer, as well as the same orientation boundary conditions, a hybrid LC
      cell containing graphene and ITO conductive layers has been prepared. The
      characteristics of LC cells with both types of conducting layers were found to be
      similar, indicating that graphene can be successfully used as a transparent
      conductive layer in LC devices.

PMID- 29354352
TI  - Magnetic field induced orientational transitions in liquid crystals doped with
      carbon nanotubes.
AB  - We propose a continuum theory of orientational phase transitions induced by an
      external magnetic field in a suspension of carbon nanotubes in a nematic liquid
      crystal. It is shown that in a magnetic field a non-uniform and two different
      uniform phases are possible in the suspension. The uniform phases of the
      suspension differ by the type of orientational coupling of nanotubes with the
      liquid crystal matrix (the planar type when the nanotubes are oriented along the
      matrix director, and the homeotropic type when the nanotubes are perpendicular to
      the director). The possibility of a redistribution of the nanotube concentration
      (segregation effect) is shown. The fields of orientational transitions between
      uniform and non-uniform phases of the suspension are found analytically. It is
      shown that, when the nanotubes are weakly coupled to the matrix, the magnetic
      field induces reentrant transitions (uniform planar phase-non-uniform phase
      uniform homeotropic phase-non-uniform phase). These transitions can be of first
      or of second order depending on the carbon nanotubes segregation intensity.

PMID- 29354353
TI  - Mineralization of high concentrations of the endocrine disruptor dibutyl
      phthalate by Fusarium culmorum.
AB  - Dibutyl phthalate (DBP) is a widely used plasticizer, whose presence in the
      environment as a pollutant raises concern because of its endocrine-disrupting
      toxicity. Growth kinetics, glucose uptake, biodegradation constant of DBP (k),
      half-life of DBP biodegradation (t1/2) and percentage of removal efficiency (%E)
      were evaluated for Fusarium culmorum grown on media containing glucose and
      different concentrations of DBP (500 and 1000 mg/l). Intermediate compounds of
      biodegraded DBP were identified by GC-MS and a novel DBP biodegradation pathway
      was proposed on the basis of the intermolecular flow of electrons of the
      intermediates identified using quantum chemical modeling. F. culmorum degraded
      99% of both 1000 and 500 mg of DBP/l after an incubation period of 168 and 228 h,
      respectively. %E was 99.5 and 99.3 for 1000 and 500 mg of DBP/l, respectively.
      The k was 0.0164 and 0.0231 h-1 for 500 and 1000 mg of DBP/l, respectively. DBP
      was fully metabolized to fumaric and malic acids, which are compounds that enter
      into the Krebs cycle. F. culmorum has a promising ability for bioremediation of
      environments polluted with DBP because it efficiently degrades DBP and uses high
      concentrations of this compound as carbon and energy source.

PMID- 29354354
TI  - Population structure and association analysis of heat stress relevant traits in
      chickpea (Cicer arietinum L.).
AB  - Understanding genetic diversity and population structure is prerequisite to
      broaden the cultivated base of any crop. In the current investigation, we report
      discovery of a total of 319 alleles by assaying 81 SSRs on 71 chickpea genotypes.
      The cluster analysis based on Jaccard coefficient and unweighted neighbor joining
      algorithm categorized all genotypes into two major clusters. Cultivars grown
      within the same agro-climatic zones were clustered together, whereas the
      remaining genotypes particularly advanced breeding lines and accessions assigned
      to another cluster. Population structure analysis separated the entire collection
      into two subpopulations (K = 2) and the clustering pattern remained in close
      agreement with those of distance-based methods. Importantly, we also discovered
      marker trait association for membrane stability index (MSI) and leaf chlorophyll
      content measured as SPAD chlorophyll meter reading (SCMR), the two important
      physiological parameters indicative of heat stress (HS) tolerance in chickpea.
      Association analysis using both general linear and mixed linear models of the
      mean phenotypic data of traits recorded in 2016 and 2017 uncovered significant
      association of NCPGR206 and H2L102 with the MSI trait. Likewise, SSR markers GA9,
      TR31 and TA113 exhibited significant association with SCMR trait. The genomic
      regions putatively linked with two traits may be investigated in greater detail
      to further improve knowledge about the genetic architecture of HS tolerance in
      chickpea.

PMID- 29354355
TI  - CTAB influenced differential elution of metagenomic DNA from saltpan and marine
      sediments.
AB  - A simple, reliable method for genomic DNA extraction from sediments with minimum
      contaminants was developed to address the risk of poor quality DNA in metagenomic
      studies. Nine DNA extraction methods using 20% cetyl-trimethyl-ammonium bromide
      (CTAB) were performed and compared to develop an extraction protocol that can
      offer humic acid-free metagenomic DNA from marine and saltpan sediments.
      Community DNA extraction was executed via., Zhou et al. modified protocol using
      20% CTAB treatment at different steps to compare the efficacy of humic acid
      removal. Out of nine DNA extraction methods, method 6 significantly improved the
      quality of DNA with efficient removal of humic substances. 16S rRNA gene
      amplification and spectrophotometric analysis confirmed the efficiency of method
      6 to remove DNA inhibitors from marine sediments as well as saltpan samples.
      Inhibitors extracted along with metagenomic DNA outcome increased DNA yield and
      PCR inhibition in method 1 and 3. However, repeated 20% CTAB wash in method 6
      ensured 16S amplification and least yield and concentration. Current study
      explains a detailed protocol based on 20% CTAB wash for the extraction of humic
      acid-free DNA from diverse sediment samples.

PMID- 29354356
TI  - Isolation, characterization and exploring biotechnological potential of
      halophilic archaea from salterns of western India.
AB  - Thirteen halophilic archaea were isolated from Kandla and Bhayander salt pans.
      These isolates were grouped into three different genera Halobacterium, Haloferax
      and Haloarcula based on morphological and biochemical characterization, polar
      lipid analysis, Amplified 16S rDNA restriction analysis (ARDRA) and 16S rDNA
      sequence analysis. Biochemical characterization suggested the ability of isolates
      to produce protease, amylase and poly-hydroxybutyrate (PHB) indicating their
      biotechnological potential. The isolates were further screened for the amount of
      extracellular protease produced. Halobacterium sp. SP1(1) showed significant
      protease production compared to other isolates. Protease producing ability of the
      isolate was influenced by several factors such as NaCl concentration, type of
      protein source, metal ions and surfactants, and presence of amino acid
      supplements in the production medium. Soybean flour, FeCl3 and
      dicotylsulfosuccinate were found to increase protease production by 2.36, 1.54
      and 1.26 folds, respectively compared to production in basal medium. Effect of
      organic solvents used in paints (n-decane, n-undecane and n-dodecane) was also
      investigated on protease production by the isolate. Protease production by
      Halobacterium sp. SP1(1) was enhanced by 1.2 folds in presence of n-decane
      compared to control. Furthermore, the ability of isolate to hydrolyse fish
      protein was investigated using three different edible fishes (Pomfret, Flat fish
      and Seer fish) as sole protein source. Pomfret was found to be a good protein
      source for protease production by the isolate. These results revealed that
      Halobacterium sp. SP1(1) may have potential for paint-based antifouling coating
      preparations and fish sauce preparation by virtue of its extracellular protease.

PMID- 29354357
TI  - Minimum cocktail of cellulolytic multi-enzyme complexes obtained from white rot
      fungi via solid-state fermentation.
AB  - The objective of this work was to optimize the total cellulase activity of the
      crude extract cocktails from five white rot fungi produced by solid-state
      fermentation, by means of the central composite design. The white rot fungi
      Pleurotus ostreatus PLO 06, Pleurotus eryngii PLE 04, Trametes versicolor TRAM
      01, Pycnosporus sanguineus PYC 02 and Phanerochaete chrysosporium PC were tested.
      For optimization process aiming at the maximum value of total cellulase activity
      (FPAse), the multi-enzyme cellulase complexes (crude extracts) of each fungus
      were mixed simultaneously in different proportions. There was increase in FPAse
      activity for the cocktails formed by the extracts of the five fungi together,
      compared to the extracts of each fungus alone. The model presented the minimum
      cocktail of enzymes for maximum total cellulase activity, with 100.00 MUL PYC;
      100.00 MUL PC; 100.00 MUL PLO06; 100.00 MUL PLE04 and 200 MUL TRAM01. The maximum
      value found was of 304.86 U/L. The result of the cocktails was very relevant,
      showing that there is an enzymatic complementation in the extracts that should be
      further studied. Concentrated extract cocktails should also be evaluated for
      biomass saccharification.

PMID- 29354358
TI  - Integrated proteome and HPLC analysis revealed quercetin-mediated inhibition of
      aflatoxin B1 biosynthesis in Aspergillus flavus.
AB  - The contamination of aflatoxins in maize or maize-related products synthesized by
      Aspergillus flavus causes severe economical loss and threat to human health. Use
      of eco-friendly phytochemicals has shown potential to inhibit secondary
      metabolites in Aspergillus species. Thus, A. flavus cultured in corn flour (CF)
      and corn flour with quercetin (CFQ) was used for protein extraction for proteome
      analysis using nLC-Q-TOF mass spectrometer. Proteome analysis revealed the
      expressions of 705 and 843 proteins in CFQ and CF, respectively. Gene Ontology
      Slim Categories (GOSC) of CF exhibited major transcriptional factors; involved in
      acetylation and deacetylation of histone proteins, carbohydrate metabolism, and
      hydrolase activity, whereas GOSC analysis of CFQ showed membrane transport
      activity, including both influx and efflux proteins. cAMP/PKA signaling pathway
      was observed in CFQ, whereas MAPK pathway in CF. To quantify biosynthesis of
      aflatoxin B1 (AFB1) in CF and CFQ, HPLC analysis at 7, 12, 24 and 48 h was
      carried out which showed decrease in AFB1 (1%) at 7-24 h in CFQ. However,
      remarkable decrease in AFB1 biosynthesis (51%) at 48 h time point was observed.
      Thus, the present study provided an insight into the mechanism of quercetin
      mediated inhibition of aflatoxin biosynthesis in A. flavus and raises the
      possibility to use quercetin as an anti-aflatoxigenic agent.

PMID- 29354359
TI  - Diversity and antagonistic potential of bacteria isolated from marine grass
      Halodule uninervis.
AB  - The aim of this study was to isolate bacteria from sea grass, Halodule uninervis
      collected from the coastal area of Jeddah, Saudi Arabia and to screen them for
      antifungal and enzymatic activities. We have isolated 162 rhizo and endophytic
      bacteria from soil, roots, and leaves of the sea grass. Antifungal screening of
      isolated bacteria revealed 19 strains (11.7%) capable to inhibit growth of four
      pathogenic fungi, Pythium ultimum, Phytophthora capsici, pyricularia oryzae, and
      Rhizoctonia solani in an in vitro assay. Taxonomic and phylogenetic analyses on
      the basis of 16S rRNA gene sequence revealed 97-99.9% sequence identity to
      recognized species. Bacillus, Staphylococcus, Jeotgalicoccus, and Planococcus,
      within the Phylum Firmicutes, Kocuria, Arthrobacter, Ornithinimicrobium and
      Corynebacterium (Actinobacteria), Sulfitobacter, Roseivivax, Ruegeria (alpha
      Proteobacteria), Moraxella, and Vibrio (gamma-Proteobacteria), were isolated.
      Strains belong to Phylum Firmicutes remain dominant antagonistic bacteria in this
      study. Further hydrolytic enzyme production was determined for these antagonistic
      bacteria. Our results demonstrated that the sea grass represents an important
      source of diverse antagonistic bacteria capable of producing antifungal
      metabolite.

PMID- 29354360
TI  - Human leukocyte antigen (HLA-F) polymorphism is associated with chronic HBV
      infection.
AB  - Human leukocyte antigen (HLA)-F has been involved in immune regulation of
      infectious diseases. However, the role of HLA-F polymorphisms in hepatitis B
      infection outcomes remains unclear. Here, we aimed to determine HLA-F
      polymorphism implication in chronic HBV. Genotype analysis was performed for
      three single nucleotide polymorphisms (SNPs) of HLA-F and one SNP of HLA-E using
      PCR-SSP, in 252 Tunisian patients with chronic HBV infection stratified according
      to their HBV DNA levels (140 patients with low HBV DNA levels < 2000 IU/mL and
      112 patients with high HBV DNA levels >= 2000 IU/mL) and 240 healthy controls
      (CTRL). The three HLA-F SNPs (HLA-F*01:02, -F*01:03 and -F*01:04) have the same
      allelic and genotypic frequencies in patients and in CTRL. We reported a low HLA
      F*01:02 and F*01:04 allelic frequencies in the Tunisian population; however, high
      HLA-F*01:03 allele frequencies were observed (17%). A significant association was
      found between the HLA-F*01:03 allele and decreased level of HBV DNA (P = 0.02 OR
      0.56, 95% CI 0.35-0.92). No significant differences were observed in haplotype
      distribution between patients and CTRL. A significant association of HLA-F*01:03
      with the level of HBV DNA suggests an important role of HLA-F in HBV replication
      control.

PMID- 29354361
TI  - Characterization and molecular modeling of Inositol 1,3,4 tris phosphate 5/6
      kinase-2 from Glycine max (L) Merr.: comprehending its evolutionary conservancy
      at functional level.
AB  - Soybean genome encodes a family of four inositol 1,3,4 trisphosphate 5/6 kinases
      which belong to the ATP-GRASP group of proteins. Inositol 1,3,4 trisphosphate
      kinase-2 (GmItpk2), catalyzing the ATP-dependent phosphorylation of Inositol
      1,3,4 trisphosphate (IP3) to Inositol 1,3,4,5 tetra phosphate or Inositol 1,3,4,6
      tetra phosphate, is a key enzyme diverting the flux of inositol phosphate pool
      towards phytate biosynthesis. Although considerable research on characterizing
      genes involved in phytate biosynthesis is accomplished at genomic and transcript
      level, characterization of the proteins is yet to be explored. In the present
      study, we report the isolation and expression of single copy Itpk2 (948 bp) from
      Glycine max cv Pusa-16 predicted to encode 315 amino acid protein with an
      isoelectric point of 5.9. Sequence analysis revealed that GmITPK2 shared highest
      similarity (80%) with Phaseolus vulgaris. The predicted 3D model confirmed 12
      alpha helices and 14 beta barrel sheets with ATP-binding site close to beta sheet
      present towards the C-terminus of the protein molecule. Spatio-temporal
      transcript profiling signified GmItpk2 to be seed specific, with higher
      transcript levels in the early stage of seed development. The present study using
      various molecular and bio-computational tools could, therefore, help in improving
      our understanding of this key enzyme and prove to be a potential target towards
      generating low phytate trait in nutritionally rich crop like soybean.

PMID- 29354362
TI  - Expression analysis of proteinase inhibitor-II under OsRGLP2 promoter in response
      to wounding and signaling molecules in transgenic Nicotiana benthamiana.
AB  - Proteinase inhibitor-II (PI-II) genes are important defense related genes that
      play critical regulatory roles in plant growth and development. In the present
      study, the expression of tomato PI-II gene was investigated under the control of
      a wound-inducible OsRGLP2 (Oryza sativa root germin like protein 2) promoter in
      transgenic tobacco plants after wounding, ABA and MeJA applications. Transcript
      level of target gene in transgenic plants was confirmed by quantitative real time
      PCR (qPCR). In response to ABA treatment at different concentrations, PI-II gene
      was strongly induced under OsRGLP2 promoter at higher concentration (100 MUM),
      while considerable level of target gene expression was observed with MeJA
      application at 50 MUM concentration. Upon wounding, relatively high PI-II gene
      expression was observed after 36-h treatment. Correspondingly, high GUS activity
      was detected at 36 h with histochemical assay and microscopic analysis in the
      vascular regions of leaves, stem and roots in wounded transgenic plants. This
      inducibility of PI-II gene by wounding, ABA and MeJA indirectly indicates its
      role in plant defense mechanism against biotic and abiotic stresses. Moreover, it
      was also suggested that ABA and MeJA dependent signaling pathways are involved in
      stimulation of PI-II gene. To the best of our knowledge, this is the first report
      describing the induction of PI-II gene under the regulation of OsRGLP2 promoter
      under stress conditions. The results of present research are useful for potential
      role of PI-II gene to improve stress tolerance in transgenic crops. Thus,
      efficacy of this gene can potentially be exploited to test the responses of
      different plants to various environmental stresses.

PMID- 29354363
TI  - Phenetic, genetic diversity and symbiotic compatibility of rhizobial strains
      nodulating pigeon pea in Northern India.
AB  - Pigeon pea (Cajanus cajan) is one of the most important legumes grown in the
      northern province of Uttar Pradesh, India. However, its productively in Uttar
      Pradesh is lower than the average yield of adjoining states. During the course of
      the present study, a survey of pigeon pea growing agricultural fields was carried
      out and it was found that 80% of plants were inadequately nodulated. The study
      was aimed to evaluate the pigeon pea symbiotic compatibility and nodulation
      efficiency of root nodulating bacteria isolated from various legumes, and to
      explore the phenetic and genetic diversity of rhizobial population nodulating
      pigeon pea growing in fields of Uttar Pradesh. Amongst all the 96 isolates, 40
      isolates showed nodulation in pigeon pea. These 40 isolates were further
      characterized by phenotypic, biochemical and physiological tests. Intrinsic
      antibiotic resistance pattern was taken to generate similarity matrix revealing
      10 phenons. The study shows that most of the isolates nodulating pigeon pea in
      this region were rapid growers. The dendrogram generated using the NTSYSpc
      software grouped RAPD patterns into 19 clusters. The high degree of phenetic and
      genetic diversity encountered is probably because of a history of mixed cropping
      of legumes. The assessment of diversity is a very important tool and can be used
      to improve the nodulation and quality of pigeon pea crop. It is also concluded
      that difference between phenetic and RAPD clustering pattern is an indication
      that rhizobial diversity of pigeon pea is not as yet completely understood and
      settled.

PMID- 29354364
TI  - Phylogeny, novel bacterial lineage and enzymatic potential of haloalkaliphilic
      bacteria from the saline coastal desert of Little Rann of Kutch, Gujarat, India.
AB  - This report describes cultivation-dependent diversity, phylogeny and enzymatic
      potential of the haloalkaliphilic bacteria isolated from the unvegetated desert
      soil of yet unexplored, saline desert of Little Rann of Kutch (LRK), India. The
      LRK is a unique ecosystem displaying a combination of Dry Rann and Wet Rann. A
      total of 25 bacteria were isolated and characterized on the basis of colony
      morphology, biochemical profile, sugar utilization, secretion of the
      extracellular enzymes and antibiotic sensitivity. Further, the identification and
      phylogenetic relatedness of 23 bacteria were established by the analysis of 16S
      rRNA gene sequences. The phylogenetic analysis indicated that the isolates belong
      to the phylum Firmicutes, comprising low G + C, Gram-positive bacteria, with
      different genera: Bacillus (~ 39%), Staphylococcus (~ 30%), Halobacillus (~ 13%),
      Virgibacillus (~ 13%), Oceanobacillus (~ 4%). Majority of the bacterial isolates
      produced proteases (30% isolates) followed by cellulases (24% isolates), CMCases
      (24% isolates) and amylases (20% isolates). Halobacillus, Virgibacillus and
      Bacillus predominantly produced hydrolases, while many produced multiple enzymes
      at high salinity and alkaline pH. Highest antibiotic resistance was observed
      against Ampicillin and Penicillin (32%) followed by Cefaclor (20%); Colistin,
      Cefoperazone and Cefotaxime (16%); Cefuroxime (12%); Gentamycin and Cefixime
      (8%); Erythromycin, Cefadroxil, Azithromycin, Co-trimoxazole, Amoxycillin,
      Norfloxacin, Cefpodoxime, Amikacin and Augmentin (4%). KJ1-10-99 and KJ1-10-93
      representing < 97% of 16S rRNA gene sequence similarity belong to a novel lineage
      within the family Bacillaceae. Comparison of the phenogram and phylogram revealed
      the contradiction of the phenogram pattern and the phylogenetic placement of the
      isolates. The isolates belonging to same species have shown considerable
      phenotypic variation. The study on the cultivable haloalkaliphilic bacteria of an
      unexplored enigmatic niche reflects ecological and biotechnological significance.

PMID- 29354366
TI  - Control of corrosive bacterial community by bronopol in industrial water system.
AB  - Abstract: Ten aerobic corrosive bacterial strains were isolated from a cooling
      tower water system (CWS) which were identified based on the biochemical
      characterization and 16S rRNA gene sequencing. Out of them, dominant corrosion
      causing bacteria, namely, Bacillus thuringiensis EN2, Terribacillus aidingensis
      EN3, and Bacillus oleronius EN9, were selected for biocorrosion studies on mild
      steel 1010 (MS) in a CWS. The biocorrosion behaviour of EN2, EN3, and EN9 strains
      was studied using immersion test (weight loss method), electrochemical analysis,
      and surface analysis. To address the corrosion problems, an anti-corrosive study
      using a biocide, bronopol was also demonstrated. Scanning electron microscopy and
      Fourier-transform infrared spectroscopy analyses of the MS coupons with biofilm
      developed after exposure to CWS confirmed the accumulation of extracellular
      polymeric substances and revealed that biofilms was formed as microcolonies,
      which subsequently cause pitting corrosion. In contrast, the biocide system, no
      pitting type of corrosion, was observed and weight loss was reduced about 32 +/-
      2 mg over biotic system (286 +/- 2 mg). FTIR results confirmed the adsorption of
      bronopol on the MS metal surface as protective layer (co-ordination of NH2-Fe3+)
      to prevent the biofilm formation and inhibit the corrosive chemical compounds and
      thus led to reduction of corrosion rate (10 +/- 1 mm/year). Overall, the results
      from WL, EIS, SEM, XRD, and FTIR concluded that bronopol was identified as
      effective biocide and corrosion inhibitor which controls the both chemical and
      biocorrosion of MS in CWS. Graphical Abstract: 

PMID- 29354365
TI  - Molecular modeling and in silico characterization of GmABCC5: a phytate
      transporter and potential target for low-phytate crops.
AB  - Designing low-phytate crops without affecting the developmental process in plants
      had led to the identification of ABCC5 gene in soybean. The GmABCC5 gene was
      identified and a partial gene sequence was cloned from popular Indian soybean
      genotype Pusa16. Conserved domains and motifs unique to ABC transporters were
      identified in the 30 homologous sequences retrieved by BLASTP analysis. The
      homologs were analyzed for their evolutionary relationship and physiochemical
      properties. Conserved domains, transmembrane architecture and secondary structure
      of GmABCC5 were predicted with the aid of computational tools. Analysis
      identified 53 alpha helices and 31 beta strands, predicting 60% residues in alpha
      conformation. A three-dimensional (3D) model for GmABCC5 was developed based on
      5twv.1.B (Homo sapiens) template homology to gain better insight into its
      molecular mechanism of transport and sequestration. Spatio-temporal real-time PCR
      analysis identified mid-to-late seed developmental stages as the time window for
      the maximum GmABCC5 gene expression, a potential target stage for phytate
      reduction. Results of this study provide valuable insights into the structural
      and functional characteristics of GmABCC5, which may be further utilized for the
      development of nutritionally enriched low-phytate soybean with improved mineral
      bioavailability.

PMID- 29354368
TI  - Fingerprinting and genetic purity assessment of F1 barley hybrids and their salt
      tolerant parental lines using nSSR molecular markers.
AB  - Hybridity and the genuineness of hybrids are prominent characteristics for
      quality control of seeds and thereby for varietal improvement. In the current
      study, the cross between two local barley genotypes (Ardhaoui: female; Testour:
      male) previously identified as susceptible/tolerant to salt stress in Tunisia was
      achieved. The hybrid genetic purity of the generated F1 putative hybrids and the
      fingerprinting of the parents along with their offspring were assessed using a
      set of 17 nuclear SSR markers. Among the analyzed loci, 11 nSSR were shown
      polymorphic among the parents and their offspring. Based on the applied 11
      polymorphic SSR loci, a total of 28 alleles were detected with an average of 2.54
      alleles per locus. The locus HVM33 presented the highest number of alleles. The
      highest polymorphism information content value was detected for the locus HVM33
      (0.6713) whereas the lowest PIC value (0.368) was revealed by the loci BMAC0156,
      EBMAC0970 and BMAG0013 with a mean value of 0.4619. The probabilities of
      identical genotypes PI for the 11 microsatellite markers were 8.63 * 10-7.
      Banding patterns among parents and hybrids showed polymorphic fragments. The 11
      SSR loci had produced unique fingerprints for each analyzed genotype and
      segregate between the two parental lines and their four hybrids. Parentage
      analysis confirms the hybrid purity of the four analyzed genotypes. Six Tunisian
      barley accessions were used as an outgroup in the multivariate analysis to
      confirm the efficiency of the employed 11 nSSR markers in genetic differentiation
      among various barley germplasms. Thus, neighbor joining and factorial analysis
      revealed clearly the discrimination among the parental lines, the four hybrids
      and the outgroup accessions. Out of the detected polymorphic 11 nuclear SSR
      markers, a set of five markers (HVM33, WMC1E8, BMAC0154, BMAC0040 and BMAG0007)
      were shown to be sufficient and informative enough to discriminate among the six
      genotypes representing the two parental lines and the four hybrids from each
      others. These five nSSR markers presented the highest number of alleles per locus
      (An), expected heterozygosity (He), PIC values and the lowest probabilities of
      identity (PI). These nSSR loci may be used as referral SSR markers for
      unambiguous discrimination and genetic purity assessment in barley breeding
      programs.

PMID- 29354367
TI  - Proteomic analysis of low-molecular-weight glutenin subunits and relationship
      with their genes in a common wheat variety.
AB  - Although many studies on low-molecular-weight glutenin subunit (LMW-GS) function
      have been reported, a comprehensive comparison between specific genes and their
      protein product is still lacking. This study aimed to link the 43 genes isolated
      from the Korean wheat variety "Jokyoung" in the authors' previous study to their
      protein products. Proteins were separated using two-dimensional gel
      electrophoresis (2-DGE) and identified by tandem mass spectrometry (MS/MS) at the
      gene haplotype level. Using MS/MS analysis of 17 protein spots, two spots were
      identified in the Glu-A3 locus and the corresponding haplotype was GluA3-13(Glu
      A3c). Six spots were identified in the Glu-B3 locus and the corresponding
      haplotypes were GluB3-33 and GluB3-43 (Glu-B3h). Eight spots were identified in
      the Glu-D3 locus and the corresponding haplotypes were GluD3-11, GluD3-21, GluD3
      31, GluD3-5, and GluD3-6 (Glu-D3a), and one spot was contaminated with gamma
      gliadin. Phylogenetic analysis and alignment of nucleotide and amino acid
      sequences assigned 35 of the 43 genes to seven haplotypes: GluA3-13, GluB3-43,
      GluD3-11, GluD3-21, GluD3-31, GluD3-42, and GluD3-5. Taken together, except for
      GluB3-33 and GluD3-6, which were not isolated, linking of each gene to the
      corresponding protein products at the gene haplotype level was accomplished using
      proteomic tools and phylogenetic analysis.

PMID- 29354369
TI  - Molecular typing of Staphylococcus aureus of different origins based on the
      polymorphism of the spa gene: characterization of a novel spa type.
AB  - The present study was conducted to determine the molecular diversity of
      Staphylococcus aureus strains isolated from human, bovine and food samples based
      on the polymorphism of the spa gene. A total of 208 S. aureus isolated from
      human, bovine raw milk and food samples were assessed using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) and single locus
      sequence typing (SLST) methods, followed by determination of spa types using
      Ridom SpaServer. Altogether, 15 distinct RFLP patterns were recorded (I-XV). The
      highest heterogeneity was observed among S. aureus isolated from humans, whereas
      most of bovine and food S. aureus isolates indicated certain RFLP patterns.
      Although most of the isolates from patients showed RFLP pattern I, none of the S.
      aureus isolated from carriers had this spa pattern. Besides, the results of SLST
      led to the characterization of 16 spa types, and one of them was a novel spa type
      which has been registered in Ridom SpaServer for the first time and designated as
      type t16929. Determination of a high number of shared RFLP patterns between human
      and food S. aureus isolates indicated possible transmission of S. aureus and the
      source of food contamination. Thus, effective hygiene measures should be taken to
      break transmission routes. However, it seems that S. aureus isolated from
      patients, carriers and bovine should be considered in a different way, since some
      isolates had similar patterns, while the others showed their own specific
      pattern.

PMID- 29354370
TI  - Enhanced biosynthesis of saponins by coronatine in cell suspension culture of
      Kalopanax septemlobus.
AB  - Kalopanax septemlobus is a medicinal woody species of the family Araliaceae, and
      the pharmaceutical properties of saponins obtained from K. septemlobus suggest
      that K. septemlobus has the potential to be a crude drug and dietary health
      supplement. In this study, we established cell suspension culture of K.
      septemlobus to develop a sustainable source of natura-ceuticals. Friable calli
      were used for establishing cell suspension culture. The maximum amount of total
      saponins (1.56 mg/60 ml suspension) was obtained during the 15th day of
      incubation, whereas the maximum capacity of saponin production was reached after
      day 6 (0.42 MUg/mg of fresh weight). The total saponin production in the cell
      suspension of K. septemlobus was significantly increased by coronatine (COR) at
      160% at a dose of 1 MUM compared with the mock-treated control, whereas methyl
      jasmonate treated cells exhibited less increase in total saponin level as
      compared to the COR-treated cells. In addition, the elicitation of COR strongly
      induced the expression of beta-amyrin synthase, thus resulting in the
      accumulation of oleanolic acid (2.369 +/- 0.98 MUg/mg of extract), a precursor
      for oleanane-type triterpene saponins. These results indicate that COR is an
      efficient elicitor for inducing phytochemicals in cell suspension culture and
      that it provides the possibility for producing saponins of K. septemlobus using
      cell suspension culture.

PMID- 29354371
TI  - High frequency plant regeneration from cotyledonary node explants of Cucumis
      sativus L. cultivar 'Green Long' via adventitious shoot organogenesis and
      assessment of genetic fidelity by RAPD-PCR technology.
AB  - Influence of cytokinins, silver nitrate (AgNO3) and auxins on plant regeneration
      from cucumber was investigated. The cotyledonary node explants were cultured on
      MS medium augmented with various concentrations (0.5-2.5 mg l-1) of 6-benzyl
      amino purine (BAP) and kinetin (KIN) for shoot bud induction. BAP at 1.5 mg l-1
      was found to be the best concentration for induction of high frequency of
      multiple shoots (98.4%). Interestingly, maximum percent of multiple shoot
      regeneration (100%) as well as number of shoot buds (54.6 shoots/culture) was
      recorded on MS medium containing the combination of 4.5 mg l-1 AgNO3 and 1.5 mg l
      1 BAP. Multiple shoot bud regeneration frequency as well as the number of shoots
      was positively correlated with the concentrations of AgNO3. Addition of silver
      nitrate in the medium not only enhanced the rate of multiple shoot bud
      regeneration but also elongation of shoot buds was observed. The highest percent
      of rooting (96.2%) was noticed on a medium containing the combination of indole 3
      butyric acid (IBA), 1.5 mg l-1 and KIN 0.5 mg l-1. Acclimatized plantlets were
      successfully established in the field where the survival rate observed was 72%.
      The RAPD profiles of in vitro regenerated plants were found to be highly
      monomorphic and identical banding pattern with mother plant. DNA fingerprinting
      results confirmed that the tissue culture plantlets were found to be true-to
      type. The present study describes efficient protocol for high frequency plant
      regeneration via adventitious shoot organogenesis in cucumber.

PMID- 29354372
TI  - Presence of 16SrIV phytoplasmas of subgroups A, D and E in planthopper Haplaxius
      crudus Van Duzee insects in Yucatan, Mexico.
AB  - The present study was carried out to determine if group 16SrIV phytoplasmas,
      causing lethal yellowing (LY) disease, are present in Haplaxius crudus Van Duzee
      (Hemiptera: Cixiidae) insects associated with palms in Yucatan, Mexico. Haplaxius
      crudus feral insects were captured from palm foliage at two locations (Chicxulub
      Puerto and CICY, Merida, where LY-type diseases are active) and evaluated
      individually for the presence of phytoplasma DNA by a group 16SrIV-specific
      nested PCR assay. The results showed positive detection in H. crudus insects in a
      proportion of 2.7% (of the total 2726 analyzed) during a 3-year period of study.
      The percentage of detection was different for each site, 5.9% positive of 799
      insects from Merida and 1.7% of 1927 from Chicxulub Puerto. Positive detections
      were also obtained in extracts from 5.3 to 1.2% of males and females,
      respectively. Sequencing and in silico RFLP and phylogenetic analyses of PCR
      amplified rDNA products indicated that H. crudus insects from Chicxulub Puerto
      harbored phytoplasma strains of subgroups 16SrIV-A or 16SrIV-D, whereas in
      insects from Merida the strains found were 16SrIV-A, 16SrIV-D or 16SrIV-E. The
      diversity of subgroup strains detected in H. crudus coincided with strains
      previously identified in palms showing LY-type disease syndromes in Yucatan
      thereby implicating H. crudus as a candidate vector of 16SrIV phytoplasmas in
      this region of Mexico.

PMID- 29354373
TI  - Assessment of three plastid DNA barcode markers for identification of
      Clinacanthus nutans (Acanthaceae).
AB  - This study was conducted to determine the feasibility of using three plastid DNA
      regions (matK, trnH-psbA, and rbcL) as DNA barcodes to identify the medicinal
      plant Clinacanthus nutans. In this study, C. nutans was collected at several
      different locations. Total genomic DNA was extracted, amplified by polymerase
      chain reaction (PCR), and sequenced using matK, trnH-psbA, and rbcL, primers. DNA
      sequences generated from PCR were submitted to the National Center for
      Biotechnology Information's (NCBI) GenBank. Identification of C. nutans was
      carried out using NCBI's Basic Local Alignment Search Tool (BLAST). The rbcL and
      trnH-psbA regions successfully identified C. nutans with sequencing rates of 100%
      through BLAST identification. Molecular Evolutionary Genetics Analysis (MEGA) 6.0
      was used to analyze interspecific and intraspecific divergence of plastid DNA
      sequences. rbcL and matK exhibited the lowest average interspecific distance
      (0.0487 and 0.0963, respectively), whereas trnH-psbA exhibited the highest
      average interspecific distance (0.2029). The R package Spider revealed that trnH
      psbA correctly identified Barcode of Life Data System (BOLD) 96%, best close
      match 79%, and near neighbor 100% of the species, compared to matK (BOLD 72%;
      best close match 64%; near neighbor 78%) and rbcL (BOLD 77%; best close match
      62%; near neighbor 88%). These results indicate that trnH-psbA is very effective
      at identifying C. nutans, as it performed well in discriminating species in
      Acanthaceae.

PMID- 29354374
TI  - Spermidine sprays alleviate the water deficit-induced oxidative stress in finger
      millet (Eleusine coracana L. Gaertn.) plants.
AB  - Severe drought stress (water deficit) in finger millet (Eleusine coracana L.
      Gaertn.) plants significantly reduced total leaf chlorophyll and relative water
      content in shoots and roots, whereas electrolyte leakage, concentrations of
      proline and hydrogen peroxide, as well as caspase-like activity were
      significantly increased. The role of spermidine in plant defence to water-stress
      was investigated after subjected to various drought treatments. Three weeks of
      daily spermidine sprays (0.2 mM) at early flowering stage significantly changed
      shoot and root growth, in both fresh and dry weights terms. At 75% of water
      deficit stress, leaves accumulated twice as much proline as unstressed plants,
      and roots accumulated thrice. Plants treated with spermidine under water stress
      showed lower electrolyte leakage, hydrogen peroxide and caspase-like activity
      than unstressed and untreated control.

PMID- 29354376
TI  - Transcriptional control of anthocyanin biosynthesis genes and transcription
      factors associated with flower coloration patterns in Gerbera hybrida.
AB  - We analyzed the expression of anthocyanin biosynthesis genes and transcription
      factors (TFs) in the Gerbera hybrida cultivars 'Bintang' and 'Alliance' that
      exhibit different coloration patterns. Differential expression of biosynthesis
      genes and TFs was associated with variable anthocyanin content at different
      flower developmental stages (S1-S3) in both cultivars; higher anthocyanin content
      was correlated with higher levels of gene expression. Exposure to different
      temperatures (6 and 22  degrees C) also resulted in different anthocyanin content
      levels: the lower temperature (6  degrees C) enhanced anthocyanin content
      compared to the higher temperature (22  degrees C). However, the increased
      anthocyanin content of 'Bintang' compared to 'Alliance' was the result of higher
      levels of expression of all detected genes, regardless of flower stage and
      temperature conditions. Therefore, we conclude that transcriptional control of
      the detected genes is associated with the mechanisms of anthocyanin biosynthesis
      and coloration patterns in gerberas; however, further studies of the key genes
      are needed.

PMID- 29354375
TI  - Comparative transcriptomics reveals a reduction in carbon capture and flux
      between source and sink in cytokinin-treated inflorescences of Jatropha curcas L.
AB  - The low seed yield of Jatropha curcas has been a stumbling block in realizing its
      full potential as an ideal bioenergy crop. Low female to male flower ratio is
      considered as a major limiting factor responsible for low seed yield in Jatropha.
      An exogenous cytokinin application was performed on floral meristems to increase
      the seed yield. This resulted in an increase of total flowers count with a higher
      female to male flower ratio. However, the seed biomass did not increase in the
      same proportion. The possible reason for this was hypothesized to be the lack of
      increased photosynthesis efficiency at source tissues which could fulfil the
      increased demand of photosynthates and primary metabolites in maturing seeds.
      After cytokinin application, possible molecular mechanisms underlying carbon
      capture and flux affected between the source and sink in developing flowers,
      fruits and seeds were investigated. Comparative transcriptome analysis was
      performed on inflorescence meristems (treated with cytokinin) and control
      (untreated inflorescence meristems) at time intervals of 15 and 30 days,
      respectively. KEGG-based functional annotation identified various metabolic
      pathways associated with carbon capture and flux. Pathways such as
      photosynthesis, carbon fixation, carbohydrate metabolism and nitrogen metabolism
      were upregulated after 15 days of cytokinin treatment; however, those were
      downregulated after 30 days. Five genes FBP, SBP, GS, GDH and AGPase showed
      significant increase in transcript abundance after 15 days of treatment but
      showed a significant decrease after 30 days. These genes, after functional
      validation, can be suitable targets in designing a suitable genetic intervention
      strategy to increase overall seed yield in Jatropha.

PMID- 29354377
TI  - Protective role of selenium against chromium stress involving metabolites and
      essential elements in Brassica juncea L. seedlings.
AB  - The present study aimed at the potential role of selenium in providing protection
      to plants subjected to chromium toxicity. The study was carried out on 15-day-old
      seedlings of Brassica juncea raised in the solutions of Cr (300 uM) and Se (2, 4
      and 6 uM), both alone and in combinations under controlled laboratory
      environment. The effects were studied on growth, plant metabolites (involved in
      osmotic homeostasis and stress protection), and essential elements. The results
      showed that the exposure of B. juncea seedlings to 300 uM Cr led to an increase
      in the contents of total sugars, reducing sugars, non-reducing sugars, total
      phenols and flavonoids. However, a significant decline in growth characteristics,
      the contents of proteins and free amino acids was observed. The essential
      elements (Na, K, Ca, Mg, C, H, N) also decreased in response to Cr. Se
      application in binary combinations, on the other hand, aided in improving seed
      germination (19%), root (88.3%) and shoot (18.2%) lengths. It also helped to
      increase the contents of sugars [total (16.3%), reducing (21.6%) and non-reducing
      (15.2%)], phenols (36.7%) and flavonoids (27.4%), thereby aiding in alleviating
      the phytotoxicity of Cr. The profiling of polyphenols and amino acids, and
      histological study of phenols supported the above results. The contents of
      essential elements also showed a significant increase, while Cr uptake was
      observed to decline by Se supplementation. The observations from the present
      study indicate that Se has the ability to influence primary and secondary
      metabolism, improve mineral nutrition and reduce Cr uptake in B. juncea seedlings
      to combat the Cr phytotoxicity and enhance the tolerance against stress.

PMID- 29354378
TI  - Unveiling the role of ATP in amplification of intrinsic peroxidase-like activity
      of gold nanoparticles.
AB  - Peroxidase enzyme-like activity of gold nanoparticles (AuNPs) is currently being
      investigated for the potential application in the several realms of biomedicines.
      However, little is explored about the peroxidase activity of AuNPs decorated with
      different surface charges. It is well-documented that the catalytic activity and
      the interaction with mammalian cells are significantly different among AuNPs
      carrying different surface charges. We have recently reported that ATP enhances
      the peroxidase-like activity of AuNPs and iron oxide nanoparticles. However, a
      comprehensive and systematic study to reveal the role of surface charge on
      nanoparticles peroxidase-like activity has not been studied. In this work, we
      have shown that AuNPs coated with PEG (PEG AuNPs), citrate (citrate AuNPs) or
      CTAB (CTAB AuNPs) exhibit varying peroxidase-like activity and the boosting
      effect imparted by ATP was also different. We found that the peroxidase-like
      activity of PEG AuNPs and citrate AuNPs is dependent on hydroxyl radical
      formation, whereas CTAB AuNPs did not show any significant activity under the
      same experimental conditions. We also studied the boosting effect of ATP on the
      peroxidase-like activity of PEG and citrate AuNPs. Although the use of ATP
      resulted in enhanced peroxidase-like activity; however, contrary to the
      expectation, it did not facilitate the enhanced production of hydroxyl radical.
      In further studies, we found that the likely mechanism of boosting effect by ATP
      is the stabilization of oxidized TMB after peroxidase reaction. ATP imparts
      stabilization to the oxidized TMB produced due to PEG AuNPs, citrate AuNPs as
      well as HRP.

PMID- 29354379
TI  - Classifying nitrilases as aliphatic and aromatic using machine learning
      technique.
AB  - ProCos (Protein Composition Server, script version), one of the machine learning
      techniques, was used to classify nitrilases as aliphatic and aromatic nitrilases.
      Some important feature vectors were used to train the algorithm, which included
      pseudo-amino acid composition (PAAC) and five-factor solution score (5FSS). This
      clearly differentiated into two groups of nitrilases, i.e., aliphatic and
      aromatic, achieving maximum sensitivity of 100.00%, specificity of 90.00%,
      accuracy of 95.00% and Mathew Correlation Coefficient (MCC) of about 0.90 for the
      pseudo-amino acid composition. On the other hand, five-factor solution score
      achieved a sensitivity of 96.00%, specificity of 84.00%, accuracy of 90.00% and
      Mathew Correlation Coefficient (MCC) of about 0.81. The total count of aliphatic
      amino acids, Ala (A), Gly (G), Leu (L), Ile (I), Val (V), Met (M) and Pro (P),
      was found to be higher, i.e., 42.7 in case of aliphatic nitrilases, whereas it
      was 40.1 in aromatic nitrilases. On the other hand, aromatic amino acids, Tyr
      (Y), Trp (W), His (H) and Phe (F) number, were found to be higher, i.e., 12.7 in
      aromatic nitrilases as compared to aliphatic nitrilases which was 10.7. This
      approach will help in predicting a nitrilase as aromatic or aliphatic nitrilase
      based on its amino acid sequence. Access to the scripts can be done logging onto
      GitHub using keyword 'Nitrilase' or 'https://github.com/rover2380/Nitrilase.git'.

PMID- 29354380
TI  - Bioethanol production from microwave-assisted acid or alkali-pretreated
      agricultural residues of cassava using separate hydrolysis and fermentation
      (SHF).
AB  - The effect of microwave (MW)-assisted acid or alkali pretreatment (300 W, 7 min)
      followed by saccharification with a triple enzyme cocktail (Cellic, Optimash BG
      and Stargen) with or without detoxification mix on ethanol production from three
      cassava residues (stems, leaves and peels) by Saccharomyces cerevisiae was
      investigated. Significantly higher fermentable sugar yields (54.58, 47.39 and
      64.06 g/L from stems, leaves and peels, respectively) were obtained after 120 h
      saccharification from MW-assisted alkali-pretreated systems supplemented (D+)
      with detoxification chemicals (Tween 20 + polyethylene glycol 4000 + sodium
      borohydride) compared to the non-supplemented (D0) or MW-assisted acid-pretreated
      systems. The percentage utilization of reducing sugars during fermentation (48 h)
      was also the highest (91.02, 87.16 and 89.71%, respectively, for stems, leaves
      and peels) for the MW-assisted alkali-pretreated (D+) systems. HPLC sugar profile
      indicated that glucose was the predominant monosaccharide in the hydrolysates
      from this system. Highest ethanol yields (YE, g/g), fermentation efficiency (%)
      and volumetric ethanol productivity (g/L/h) of 0.401, 78.49 and 0.449 (stems),
      0.397, 77.71 and 0.341 (leaves) and 0.433, 84.65 and 0.518 (peels) were also
      obtained for this system. The highest ethanol yields (ml/kg dry biomass) of ca.
      263, 200 and 303, respectively, for stems, leaves and peels from the MW-assisted
      alkali pretreatment (D+) indicated that this was the most effective pretreatment
      for cassava residues.

PMID- 29354381
TI  - The production of UL16-binding protein 1 targeted pigs using CRISPR technology.
AB  - Two sgRNAs were designed to target the region of exon 2 of the pULBP1 gene by
      microinjection. The co-injection of modified Cas9-D10A nickase with a pair of
      sgRNAs into the zygote's cytoplasm easily and efficiently generated biallelic
      modification of the pULBP1 gene in one step. Five out of nine F0 generation
      piglets showed insertions or deletions in the targeting site of the pULBP1 gene,
      indicating that pULBP1 mutation efficiency reached about 56% (5/9). Quantitative
      determination of pULBP1 showed approximately a 1.53-fold reduction in the amount
      of protein ULBP1 on the cell surface (ELISA). A human NK-cell cytotoxicity test
      leads to the conclusion that higher cell viability is observed for -/- ULBP1
      (survival rate 85.36%) compared to +/+ ULBP1 (69.58%). ULBP1-KO pigs will provide
      a more progressive xenograft source for further research studies, especially
      those measuring the effects of abolishing the gene function in terms of the
      complexity of the immunological interactions.

PMID- 29354382
TI  - Production of gellan gum, an exopolysaccharide, from biodiesel-derived waste
      glycerol by Sphingomonas spp.
AB  - In the present study, biodiesel-derived waste glycerol (WG) was used for the
      isolation and production of gellan, an exopolysaccharide, on media containing WG
      as the main carbon source. Two bacterial isolates showed gellan producing
      potential which were identified as Sphingomonas pseudosanguinis (Accession No.
      GI:724472387) and Sphingomonas yabuuchiae (GI:724472388) by 16S rRNA gene
      sequencing. To maximize gellan production by S. pseudosanguinis and S.
      yabuuchiae, media optimization was performed at different pHs and glycerol
      concentrations. Morphological observations through microscopic images showed the
      production of gellan from these isolates. Simple linear regression showed better
      utilization of WG by S. pseudosanguinis than S. yabuuchiae at pH 6 and pH 7.
      Though, both the strains showed reverse trend at pH 8. Both the strains were able
      to produce high amounts of gellan gum (51.6 and 52.6 g/l, respectively) using WG
      (80 g/l) as the sole carbon source, in a minimal medium. This is the first report
      on the efficient degradation of WG and low-cost production of gellan. Owing to
      these characteristics, S. pseudosanguinis and S. yabuuchiae demonstrate great
      potential for use in the commercial production of gellan and in the
      bioremediation of WG.

PMID- 29354383
TI  - Calligonum comosum and Fusarium sp. extracts as bio-mediator in silver
      nanoparticles formation: characterization, antioxidant and antibacterial
      capability.
AB  - In the current study, extracellular biosynthesis of silver nanoparticles (AgNPs)
      was carried out using aqueous extracts of green Calligonum comosum stem, besides
      Fusarium sp. Synthesized AgNPs were characterized using ultraviolet (UV)-Vis
      spectrophotometer, transmission electron microscopy (TEM) and zeta potential.
      Moreover, biosynthesized AgNPs were estimated for the scavenging ability on DPPH
      radical as well as tested for their antibacterial activity using well diffusion
      method against Gram-positive bacteria Staphylococcus aureus. On the other hand,
      DNA content from untreated and AgNPs treated bacterial cells was evaluated by
      (UV)-Vis spectrophotometer and agarose gel electrophoresis. Results revealed the
      formation of AgNPs, which was first detected by color change of the reaction
      mixture. The characteristic surface plasmon resonance absorption was detected at
      450 and 410 nm for the plant and myco-synthesized AgNPs. Furthermore, TEM
      micrograph and zeta sizer showed formation of spherical particles with an average
      size of about 105.8 and 228.4 nm for plant and myco-synthesized AgNPs,
      respectively. Plant-synthesized AgNPs exhibited higher scavenging of DPPH
      radicals than that of the myco-synthesized one. For bactericidal action, plant
      synthesized AgNPs showed higher inhibition zone compared with myco-synthesized
      one, which was negatively correlated with the nanoparticle size. Furthermore, low
      DNA concentration was detected for AgNPs treated bacteria, which might be a
      consequence of inactivation for DNA replication. Further experimental work is
      required to find out if there is any correlation between nanoparticles size and
      efficacy against bacteria.

PMID- 29354384
TI  - Survey of sulfur-oxidizing bacterial community in the Pearl River water using
      soxB, sqr, and dsrA as molecular biomarkers.
AB  - In this study, we surveyed the abundance and diversity of three sulfur oxidation
      genes (sqr, soxB, and dsrA) using quantitative assays and Miseq high-throughput
      sequencing. The quantitative assays revealed that soxB is more abundant than sqr
      and dsrA and is the main contributor to sulfur oxidation. In the diversity
      analysis, the SOB community mainly comprised the classes Nitrospira,
      Alphaproteobacteria, Betaproteobacteria, and Gammaproteobacteria. The genera
      Gallionella, Hydrogenophaga, Limnohabitans, Methylomonas, Nitrospira, Rhodoferax,
      and Sulfuritalea were abundant in the communities for sqr; Dechloromonas,
      Limnohabitans, Paracoccus, Sulfuritalea, Sulfitobacter, and Thiobacillus were
      abundant in communities for soxB; Sulfuritalea, Sulfurisoma, and Thiobacillus
      were abundant in communities for dsrA. This study presented a high diversity of
      SOB species and functional sulfur-oxidizing genes in Pearl River via high
      throughput sequencing, suggesting that the aquatic ecosystem has great potential
      to scavenge the sulfur pollutants by itself.

PMID- 29354385
TI  - Nanotechnology: current uses and future applications in the food industry.
AB  - Recent advances in nanoscience and nanotechnology intend new and innovative
      applications in the food industry. Nanotechnology exposed to be an efficient
      method in many fields, particularly the food industry and the area of functional
      foods. Though as is the circumstance with the growth of any novel food processing
      technology, food packaging material, or food ingredient, additional studies are
      needed to demonstrate the potential benefits of nanotechnologies and engineered
      nanomaterials designed for use in foods without adverse health effects.
      Nanoemulsions display numerous advantages over conventional emulsions due to the
      small droplets size they contain: high optical clarity, excellent physical
      constancy against gravitational partition and droplet accumulation, and improved
      bioavailability of encapsulated materials, which make them suitable for food
      applications. Nano-encapsulation is the most significant favorable technologies
      having the possibility to ensnare bioactive chemicals. This review highlights the
      applications of current nanotechnology research in food technology and
      agriculture, including nanoemulsion, nanocomposites, nanosensors, nano
      encapsulation, food packaging, and propose future developments in the developing
      field of agrifood nanotechnology. Also, an overview of nanostructured materials,
      and their current applications and future perspectives in food science are also
      presented.

PMID- 29354386
TI  - Molecular characterization of 5' UTR of the lycopene epsilon cyclase (lcyE) gene
      among exotic and indigenous inbreds for its utilization in maize
      biofortification.
AB  - Maize grains are the important source of food and energy, but possess very low
      proA (< 2.5 ug/g) compared to target level of 15 ug/g set by HarvestPlus to
      alleviate VAD. Favorable allele having variation in 5' untranslated region (UTR)
      of lycopene epsilon cyclase (lcyE) gene enhances concentration of proA in maize.
      To identify the sequence variation in 5' UTR of lcyE, a set of diverse 13 inbreds
      of indigenous and exotic origin was characterized for allelic constitution of
      lcyE. Inbreds possessed wide variation in proA (1.62-23.12 ug/g) with a mean of
      9.64 ug/g. The proA in CIMMYT-HarvestPlus genotypes having favorable allele of
      lcyE was very high (22.28 ug/g), whereas the Indian inbreds with the same allele
      possessed very low proA (2.48 ug/g). Eight genotypes viz., HKI161, HKI163, HKI161
      PV, HKI163-PV, HKI193-1-PV, HKI193-2-PV, HP704-22 and HP704-23 revealed the
      presence of favorable allele, while VQL1, DMRIL47, MGU-PV-123/C6, HKI193-1 and
      HKI193-2 showed the presence of unfavorable allele of lcyE gene. Sequence
      comparison of favorable allele of Indian (HKI161 and HKI163) and exotic genotypes
      (HP704-22 and HP704-23) revealed seven SNPs having three transitions (SNP1 and
      SNP3: G to A, SNP2: C to T) and four transversions (SNP4: C to G, SNP5: T to G,
      SNP6: G to C and SNP7: G to T). Four SNPs (SNP1: position 446, SNP2: position
      458, SNP3: position 459 and SNP4: position 483) discriminated the low- and high-
      proA lines having favorable allele of lcyE 5'TE. These SNPs hold significance in
      enrichment of proA in maize for marker development and their use in marker
      assisted selection.

PMID- 29354387
TI  - Simultaneous detection of Escherichia coli O157:H7, Staphylococcus aureus and
      Salmonella by multiplex PCR in milk.
AB  - Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella are food-borne
      pathogens that cause serious gastrointestinal illness and frequent food safety
      accidents. This study aimed to develop a practical multiplex polymerase chain
      reaction (mPCR) technique for the simultaneous detection of these food-borne
      pathogens in culture broth and artificial food matrix. Pathogen-specific DNA
      sequences in the rfbE, nuc, and invA genes were used as targets to design primers
      for the identification of E. coli O157:H7, S. aureus, and Salmonella,
      respectively. As expected, the method produced species-specific bands of
      amplified products without any contaminating non-specific bands. The highest
      species specificity was established with primer concentrations of 0.1, 0.2, and
      0.4 MUM for E. coli O157:H7, S. aureus, and Salmonella, correspondingly. The
      detection sensitivity of this assay was 103 CFU/mL in culture broth, and the
      limit of detection was consistent with singleplex PCR in the food sample. The
      mPCR assay proposed here is an easy and convenient detection method, which will
      be valuable for microbial epidemiology and food safety investigations.

PMID- 29354388
TI  - Evaluation of plant-based natural coagulants for municipal wastewater treatment.
AB  - In this study, four plant-based natural coagulants (banana peel powder, banana
      stem juice, papaya seed powder and neem leaf powder) were evaluated for the
      removal of turbidity, chemical oxygen demand (COD) and total suspended solids
      (TSS) from municipal wastewater. The experiments were conducted at room
      temperature without adjusting the initial pH. The maximum turbidity removal was
      observed with banana peel powder (59.6%) at 0.4 g/L of dosage. Papaya seed powder
      and banana stem juice were the most effective for TSS removal (66.66%) and COD
      removal (66.67%), respectively. Significant linear relationships between
      turbidity and TSS (R2 = 0.67-0.88) and turbidity removals and COD removals (R2 =
      0.68-0.8) were observed. Interestingly, all the natural coagulants tested in the
      study did not change the pH of the wastewater, which is an added advantage. FTIR
      analysis of banana peels revealed that functional groups such as carboxylic acid,
      hydroxyl and aliphatic amines might be responsible for promoting the coagulation
      flocculation by neutralizing the charge on impurities in water. Overall, the
      results suggest the potential of low-cost natural coagulants in municipal
      wastewater treatment.

PMID- 29354389
TI  - Computer-Based Prevention and Intervention to Reduce Substance Use in Youth.
AB  - Purpose of Review: Computer-based programs for substance use prevention and
      intervention among youth are on the ascendancy. Whether delivered by computer per
      se or by electronic tablet or smartphone, technology-driven programs are
      harmonious with how young people access information and interact with their
      worlds. This review examines recent evidence on computer-based programs aimed at
      substance use among youth, with particular attention to results from randomized
      trials. Recent Findings: Outcome studies of computer-based, substance use-related
      programs published over the past 5 years reveal mixed results amidst diverse
      intervention approaches and delivery settings. Many studies are marred by high
      attrition. Notable in the recent literature is the international nature of
      technology-driven substance use prevention and intervention programs. With some
      exceptions, most programs appear to not have been customized for their recipient
      populations. Though few in number, the highest-quality studies of computer-based
      programs show positive outcomes in reduced substance use rates. Summary: Based on
      recent findings, considerable work needs to happen before computer-delivered
      approaches are a proven means for reducing substance use among youth. Original
      programs, expressly developed for subgroups of youth, are in short supply. Though
      controlled designs are becoming commonplace, too many studies of computer-based
      programs suffer from flaws-including high rates of attrition-that limit the
      discovery of positive outcomes.

PMID- 29354391
TI  - Extensive Metastatic Sarcomatoid Renal Cell Carcinoma Evaluated by 18F-FDG
      PET/CT: a Case Report and Review of Literature.
AB  - Sarcomatoid renal cell carcinoma (sRCC) is a highly aggressive form of
      dedifferentiated renal cell carcinoma. We report a 62-year-old man who presented
      with respiratory symptoms and a lung mass on chest computed tomography (CT). The
      patient underwent positron emission tomography/computed tomography (PET/CT) with
      18F-fluorodeoxyglucose (18F-FDG) and was found to have extensive metastatic
      disease. Based on the history and imaging findings, there were possible primary
      malignancies, including bronchogenic carcinoma, melanoma, or an aggressive
      lymphoma. An excisional biopsy surprisingly revealed a high-grade sarcomatoid
      carcinoma with no evidence of differentiation, and immunohistochemical (IHC)
      studies showed that the tumor cells were positive for markers of genitourinary
      origin (PAX-8 and vimentin). The histologic and IHC results, along with multiple
      FDG-avid exophytic lesions in both kidneys, were considered diagnostic of sRCC.
      Here we have highlighted the potential role of 18F-FDG-PET-CT in patients with
      sRCC, discussed the diagnostic challenges, and presented a brief review.

PMID- 29354392
TI  - Adolescents in Multi-Ethnic Families under Korean Ethnic Nationalism.

PMID- 29354393
TI  - Effect of Obesity on Blood Pressure and Arterial Stiffness in Middle-Aged Korean
      Women.
AB  - Objectives: Our study aims to provide basic scientific data on the importance of
      obesity management in middle-aged Korean women by analyzing its effects on blood
      pressure and arterial stiffness. In addition, we examined the correlations of
      these two parameters. Methods: The study participants were 40 middle-aged female
      volunteers, who were classified into obesity group (n = 20) and normal weight
      group (n = 20). Statistical analysis was performed using independent t-test and
      the Pearson correlation coefficient was used to correlate blood pressure and
      arterial stiffness. Results: This study evaluated the systolic blood pressure,
      diastolic blood pressure, and pulse wave velocity (PWV). These results were
      higher in the obesity group than the normal weight group. Furthermore, blood
      pressure and arterial stiffness (PWV, augmentation pressure) were static
      correlated. Conclusion: Obesity is closely related to blood pressure and arterial
      stiffness. Therefore, indices for blood pressure and arterial stiffness may play
      a vital role in predicting and preventing obesity and its sequelae.

PMID- 29354390
TI  - Radiotherapy and Glioma Stem Cells: Searching for Chinks in Cellular Armor.
AB  - Purpose of the review: Radiation became a pillar of oncologic treatment in the
      last century and provided a powerful and effective locoregional treatment of
      solid malignancies. After achieving some of the first cures in lymphomas and skin
      cancers, it assumed a key role in curative treatment of epithelioid malignancies.
      Despite success across a variety of histologic types, glioblastoma (GBM), the
      most common primary brain tumor afflicting adults, remains ultimately resistant
      to current radiation strategies. While GBMs demonstrate an initial response,
      recurrence is essentially universal and fatal, and typically reoccur in the areas
      that received the most intense radiation. Recent Findings: Glioma stem cells
      (GSCs), a subpopulation of tumor cells with expression profiles similar to neural
      stem cells and marked self-renewal capacities, have been shown to drive tumor
      recurrence and preclude curative radiotherapy. Recent research has shown that
      these cells have enhanced DNA repair capacity, elevated resistance to cytotoxic
      ion fluxes and escape multi-modality therapies. Summary: We will analyze the
      current understanding of GSCs and radiation by highlighting key discoveries
      probing their ability to withstand radiotherapy. We then speculate on novel
      mechanisms by which GSC can be made sensitive to or specifically targeted by
      radiation therapy.

PMID- 29354394
TI  - Effects of Timely Control Intervention on the Spread of Middle East Respiratory
      Syndrome Coronavirus Infection.
AB  - Objectives: The 2015 Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
      outbreak in Korea caused major economic and social problems. The control
      intervention was conducted during the MERS-CoV outbreak in Korea immediately
      after the confirmation of the index case. This study investigates whether the
      early risk communication with the general public and mass media is an effective
      preventive strategy. Methods: The SEIR (Susceptible, Exposed, Infectious,
      Recovered) model with estimated parameters for the time series data of the daily
      MERS-CoV incidence in Korea was considered from May to December 2015. For 10,000
      stochastic simulations, the SEIR model was computed using the Gillespie
      algorithm. Depending on the time of control intervention on the 20th, 40th, and
      60th days after the identification of the index case, the box plots of MERS-CoV
      incidences in Korea were computed, and the results were analyzed via ANOVA.
      Results: The box plots showed that there was a significant difference between the
      non-intervention and intervention groups (the 20th day, 40th day, and 60th day
      groups) and seemed to show no significant difference based on the time of
      intervention. However, the ANOVA revealed that early intervention was a good
      strategy to control the disease. Conclusion: Appropriate risk communication can
      secure the confidence of the general public in the public health authorities.

PMID- 29354395
TI  - Korean Adolescents' Health Behavior and Psychological Status according to Their
      Mother's Nationality.
AB  - Objectives: This study was conducted to compare adolescents' health behaviors and
      psychological status according to whether or not their mother was born in Korea.
      Methods: This secondary analysis used nationally representative data from the
      2015 Korean Youth Risk Behavior Web-based Survey. The self-administered
      questionnaire included computer measured socio-demographic variables, 15 health
      behaviors, and psychological status. Data from 65,426 middle school and high
      school students were analyzed. Multiple logistic regression, adjusting for socio
      demographic variables, was used to analyze differences in health behaviors and
      psychological status between adolescents with a foreign-born mother and those
      with a Korean mother. Results: Adolescents who have foreign-born mothers had a
      lower level of current drinking and subjective happiness, but a higher stress
      level. Conclusion: The stress levels of the adolescents with foreign-born mothers
      could be affected by their multicultural background. It is necessary to analyze
      stress-influencing factors of multicultural adolescents by comparing them to
      adolescents from Korean parents. Additionally, our society should pay more
      attention to the mental health of multicultural adolescents. Schools should also
      make various efforts to protect multicultural adolescents by adopting mental
      health management programs led by school nurses and counselors.

PMID- 29354396
TI  - Epidemiological Study on Candida Species in Patients with Cancer in the Intensive
      Care Unit.
AB  - Objectives: Although cancer survival rates have increased, serious infection
      complications can arise in cancer patients. Candida can occur in various tissues
      and has significant effects on the prognosis of patients with cancer. Thus, we
      conducted an epidemiological study on Candida infections in patients with cancer
      admitted to the intensive care unit. Methods: A retrospective study was conducted
      in adult patients with cancer admitted to the intensive care unit between January
      1, 2013, and December 31, 2015. Candida infection status and predictive factors
      for mortality were examined in 634 patients. Results: The predictive factors for
      mortality included the use of steroids, use of a central venous catheter or
      mechanical ventilator, and identification of Candida in the blood. Patients who
      stayed in the surgical and intensive care unit for more than 7 days had a lower
      risk of death than that in those with shorter days. Conclusion: The present study
      shows that invasive procedures, bloodstream infections, and the use of steroids
      increase the risk of mortality in Candida-infected patients with cancer. To
      improve the quality of life and reduce mortality, further studies are needed on
      the factors affecting the risk of mortality associated with Candida infection.

PMID- 29354397
TI  - Development of a New Approach to Determine the Potency of Bacille Calmette-Guerin
      Vaccines Using Flow Cytometry.
AB  - Objectives: To circumvent the limitations of the current golden standard method,
      colony-forming unit (CFU) assay, for viability of Bacille Calmette-Guerin (BCG)
      vaccines, we developed a new method to rapidly and accurately determine the
      potency of BCG vaccines. Methods: Based on flow cytometry (FACS) and fluorescein
      diacetate (FDA) as the most appropriate fluorescent staining reagent, 17 lots of
      BCG vaccines for percutaneous administration and 5 lots of BCG vaccines for
      intradermal administration were analyzed in this study. The percentage of viable
      cells measured by flow cytometry along with the total number of organisms in BCG
      vaccines, as determined on a cell counter, was used to quantify the number of
      viable cells. Results: Pearson correlation coefficients of FACS and CFU assays
      for percutaneous and intradermal BCG vaccines were 0.6962 and 0.7428,
      respectively, indicating a high correlation. The coefficient of variation value
      of the FACS assay was less than 7%, which was 11 times lower than that of the CFU
      assay. Conclusion: This study contributes to the evaluation of new potency test
      method for FACS-based determination of viable cells in BCG vaccines. Accordingly,
      quality control of BCG vaccines can be significantly improved.

PMID- 29354398
TI  - Effects of Anti-Smoking Public Service Announcements on the Attitudes of Korean
      College Students toward Smoking.
AB  - Objectives: This study aimed to identify the effects of anti-smoking public
      service announcements on the attitudes of Korean college students toward smoking.
      Methods: This study involved students via convenience sampling from seven
      universities who were randomly assigned to four groups. All groups completed a
      preliminary questionnaire, before being shown a public service announcement
      twice, and then completed a post viewing questionnaire. Results: For
      announcements with positive messages, the proportion of changes in beliefs and
      attitudes were 39.1% and 19.8%, respectively, whereas those with negative
      messages showed a greater proportion of changes in the beliefs (59.7%) and
      attitudes (40.3%). After adjusting for sex and change in belief, the message
      types and smoking status were identified as factors affecting the change in the
      participants attitudes. A negative message resulted in a greater change in
      attitudes (odds ratio [OR], 3.047; 95% confidence interval [CI], 1.847-5.053).
      Ever-smokers including current smokers showed a greater positive change in
      attitude than never-smokers (OR, 6.965; 95% CI, 4.107-11.812). Conclusion: This
      study found that positive anti-smoking public service announcements were more
      effective on attitude change than negative messages. Additionally these
      announcements were more effective among viewers who were current smokers or had a
      prior smoking experience.

PMID- 29354399
TI  - Relationship between Alcohol Purchasing Time and Alcohol Use Disorder in South
      Korea.
AB  - Objectives: Currently, time of alcohol purchase is not part of the policies to
      regulate alcohol consumption in South Korea. This study was conducted to
      determine the relationship between alcohol purchasing time and alcohol use
      disorder. Methods: The survey for this study was conducted in geographically
      diverse regions of South Korea in 2012. Respondents' purchasing behaviors for
      both on-licensed (i.e., allows for consumption within the premises) and off
      licensed (i.e., where alcohol is consumed off the premises) outlets and time of
      alcohol consumption were collected. Alcohol consumption patterns were examined
      using the Rapid Alcohol Problem Screen 4 (RAPS4). Data were also analyzed by age,
      gender and purchasing time. Results: Results showed that among the off-licensed
      premises, supermarkets appear to be the most popular venue while for on-licensed
      premises; alcohol was generally consumed inside hotels/pubs regardless of age and
      gender of the purchaser. Purchasing of alcohol was highest during the day and
      early evening period (9:00 a.m. to 9:59 p.m.). Females are most likely to abuse
      alcohol than males during the early morning period and is that period after 12:00
      midnight. Conclusion: Analysis suggests that the survey instrument used in the
      International Alcohol Control Study is being used to collect data on alcohol
      purchasing time consumption; therefore, the potential is there to provide
      accurate results to contribute appropriate policy responses to reduce alcohol
      related-harm.

PMID- 29354400
TI  - In Vitro Antiviral Activity of Sakuranetin against Human Rhinovirus 3.
AB  - Objectives: Rhinoviruses (RVs) cause common cold and are associated with
      exacerbation of chronic inflammatory respiratory diseases. Until now, no
      clinically effective antiviral chemotherapeutic agents to treat diseases caused
      by human rhinoviruses (HRVs) have been reported. We assessed the anti-HRV3
      activity of sakuranetin isolated from Sorbus commixta Hedl. in human epithelioid
      carcinoma cervix (HeLa) cells, to evaluate its anti-rhinoviral potential in the
      clinical setting. Methods: Antiviral activity and cytotoxicity as well as the
      effect of sakuranetin on HRV3-induced cytopathic effects (CPEs) were evaluated
      using the sulforhodamine B (SRB) method using CPE reduction. The morphology of
      HRV3-infected cells was studied using a light microscope. Results: Sakuranetin
      actively inhibited HRV3 replication and exhibited antiviral activity of more than
      67% without cytotoxicity in HeLa cells, at 100 MUg/mL. Ribavirin showed anti-HRV3
      activity similar to that of sakuranetin. Treatment of HRV-infected HeLa cells
      with sakuranetin visibly reduced CPEs. Conclusion: The inhibition of HRV
      production by sakuranetin is mainly due to its general antioxidant activity
      through inhibition of viral adsorption. Therefore, the antiviral activity of
      sakuranetin should be further investigated to elucidate its mode of action and
      prevent HRV3-mediated diseases in pathological conditions.

PMID- 29354401
TI  - Follow-up Study of Patients Previously Diagnosed with Lymphatic Filariasis in
      Korea.
AB  - Objectives: Korea was an endemic area for lymphatic filariasis (LF), caused by
      the nematode parasite Brugia malayi, until the 1970s. The World Health
      Organization recognized Korea as LF-free in June 2008. However, it is necessary
      to confirm that patients that have had LF in the past still test negative, to
      prevent the re-emergence of LF in Korea. Methods: We followed up a total of 83
      patients who had been diagnosed with LF between 2002 and 2010 in endemic LF
      areas. Results: Fifty-two of the 83 subjects were negative for LF, whereas 31
      subjects had re-located to a different city or province, were dead, or were
      unaccounted for. Most subjects with negative test results still exhibited edema
      in the legs or the arms, and some complained of redness and swelling in the legs
      or ankle joints. However, we found that these symptoms were due to diseases other
      than LF. Conclusion: In this follow-up study, we did not find any evidence
      indicating the potential re-emergence of LF in Korea.

PMID- 29354403
TI  - Endoscopic Interdigital Neurectomy of the Foot.
AB  - Morton's neuroma is a compressive neuropathy resulting in perineural fibrosis
      rather than a neuroma of the plantar digital nerve. Surgical treatment is
      indicated for patients with a clear diagnosis of Morton's neuroma and no
      improvement with nonsurgical treatment. The surgical options include isolated
      intermetatarsal ligament division, isolated interdigital nerve excision, and
      interdigital nerve excision with intermetatarsal ligament division, with or
      without submuscular transposition. This can be performed via dorsal or plantar
      approach. The open approaches require long incisions and extensive soft-tissue
      dissection. The purpose of this Technical Note is to describe the surgical
      details of endoscopic interdigital neurectomy. This is an endoscopic approach
      involving interdigital nerve excision with intermetatarsal ligament division and
      submuscular transposition.

PMID- 29354404
TI  - Lateral Ulnar Collateral Ligament Reconstruction for Posterolateral Rotatory
      Instability of the Elbow.
AB  - Reconstruction of the lateral ulnar collateral ligament of the elbow is the
      primary treatment for recurrent symptomatic posterolateral rotatory instability.
      Although a number of lateral ulnar collateral ligament reconstruction techniques
      have been described, the docking technique has received general acceptance. In
      this technique, the graft is passed through a tunnel on the ulnar side and the 2
      free limbs are docked into the humerus at the isometric point on the lateral
      condyle. Advantages of this method of reconstruction include reduced bone
      removal, decreased soft tissue damage, and precise control of graft tensioning.
      When precise surgical steps are followed, this technique can be performed in a
      reliable, efficient, and reproducible manner for patients with posterolateral
      rotatory instability of the elbow.

PMID- 29354405
TI  - Arthroscopic Pancapsular Shift With Labral Repair for Multidirectional
      Instability of the Shoulder.
AB  - Initial treatment of shoulder multidirectional instability (MDI) consists of
      nonoperative modalities of physical therapy and rehabilitation; if this fails,
      surgical treatment can become necessary. MDI of the shoulder can be challenging
      to manage in individuals who fail conservative management. Historically, surgical
      treatment for MDI has been open capsular plication; however, arthroscopic
      capsular plication has now become the standard of care, with outcomes similar to
      the open procedure. The purpose of this article and Video 1 is to describe our
      arthroscopic technique for pancapsular shift with labral repair.

PMID- 29354406
TI  - Office-Based Needle Arthroscopy: A Standardized Diagnostic Approach to the Knee.
AB  - Surgical knee arthroscopy is among the most commonly performed procedures in the
      United States. The decision to treat is often based on clinical examination and
      magnetic resonance imaging. Equivocal results frequently require patients to
      undergo surgical arthroscopy, exposing the patient to inherent risks and
      potential surgical complications. Office-based needle arthroscopy provides an
      alternative approach to visualizing intra-articular anatomy and pathology in real
      time. The purpose of this article is to provide a standardized diagnostic
      approach to needle arthroscopy of the knee.

PMID- 29354402
TI  - Role of calcium channels in bipolar disorder.
AB  - Bipolar disorder is characterized by a host of sleep-wake abnormalities that
      suggests that the reticular activating system (RAS) is involved in these
      symptoms. One of the signs of the disease is a decrease in high frequency gamma
      band activity, which accounts for a number of additional deficits. Bipolar
      disorder has also been found to overexpress neuronal calcium sensor protein 1
      (NCS-1). Recent studies showed that elements in the RAS generate gamma band
      activity that is mediated by high threshold calcium (Ca2+) channels. This mini
      review provides a description of recent findings on the role of Ca2+ and Ca2+
      channels in bipolar disorder, emphasizing the involvement of arousal-related
      systems in the manifestation of many of the disease symptoms. This will hopefully
      bring attention to a much-needed area of research and provide novel avenues for
      therapeutic development.

PMID- 29354407
TI  - Biceps Tenodesis: Anatomic Tensioning.
AB  - Biceps tenodesis is a commonly employed surgical intervention for refractory
      symptoms related to the biceps-labral complex, those intra-articular and those
      within the extra-articular bicipital tunnel. While a litany of surgical
      techniques exists, the optimal method for ensuring an anatomic length-tension
      relationship during tenodesis remains elusive. Appropriate tensioning may limit
      undesirable outcomes such as cramping or cosmetic deformity. We describe herein
      our technique as a simple and efficient means to establish patient-specific,
      anatomic tensioning of the long head of the biceps during tenodesis.

PMID- 29354408
TI  - Arthroscopic Repair of a Circumferential 360 degrees  Labral Tear.
AB  - Injuries to the glenoid labrum can result in shoulder instability and pain. These
      lesions may occur anywhere around the glenoid labrum, and thus, the arthroscopist
      must be prepared to approach all aspects of the glenoid from multiple angles. The
      pan-labral or circumferential (360 degrees ) tear of the glenoid labrum presents
      a unique challenge to even the experienced arthroscopist. The extent of the
      lesion requires the use of accessory portals and percutaneous techniques to
      establish adequate visualization and to facilitate the proper trajectory for
      anchor placement. The pan-labral tear also demands intraoperative planning
      throughout the repair to ensure proper tensioning and alignment of the labrum and
      capsular tissue. The purposes of this article are to report a technique for
      repairing a pan-labral lesion and to emphasize the use of accessory portals and
      percutaneous techniques for complete access to the glenoid.

PMID- 29354409
TI  - Video-Assisted Thoracoscopic Surgery for Drainage of Dorsal Paravertebral
      Abscess.
AB  - Tuberculosis of the spine is the second most common extrapulmonary presentation
      of the disease and is associated with significant morbidity. The drainage of the
      abscess may be needed in patients who fail to respond to medical treatment and
      present with a significant or deteriorating neurologic status. The dorsal spine
      gives a unique opportunity for decompression alone as it is supported by the rib
      cage, decreasing the chances of collapse. Drainage of the abscess in the dorsal
      spine usually needs an open thoracotomy. Open thoracotomy is associated with
      increased blood loss, pain, and increased postoperative rehabilitation period.
      Video-assisted thoracoscopic surgery (VATS) is an excellent alternative for
      decompression of dorsal paraspinal abscess with significantly decreased blood
      loss, soft tissue dissection, scarring, and hospital stay. Overall, this leads to
      significantly decreased postoperative morbidity and faster recovery. The purpose
      of this article was to describe the indications and procedure of VATS for
      drainage of dorsal spine paravertebral abscess.

PMID- 29354410
TI  - Opening Wedge High Tibial Osteotomy Using Combined Computed Tomography-Based and
      Image-Free Navigation System.
AB  - For opening wedge high tibial osteotomy (OWHTO), it is recommended that the
      osteotomy line is parallel to the medial tibial posterior slope (TPS) in the
      sagittal view and that the alignments are simultaneously controlled in the
      coronal and sagittal views. Here combined computed tomography (CT)-based and
      image-free navigation systems were used for intraoperative reference during
      OWHTO. Using the CT-based navigation, 2 entry points for insertion of Kirschner
      wires were preoperatively set up and an accurate osteotomy plane was
      intraoperatively duplicated. Preoperative planning anticipated a femorotibial
      angle of 170 degrees , representing a weight-bearing ratio of 62.5%, on the whole
      leg radiograph. The original TPS in the sagittal view was aimed to be preserved
      postoperatively. The hip-knee-ankle (HKA) correction angle was preoperatively
      measured on the whole-leg radiograph, and the HKA angle and flexion angle were
      intraoperatively monitored in real time using the image-free navigation. We have
      introduced an operative technique for OWHTO using CT-based and image-free
      navigation systems. We expect that this method, with the osteotomy plane parallel
      to the tibial plateau plane in the sagittal view and simultaneous control of
      coronal and sagittal alignments, will enable actuation of accurate alignment in
      the 2 planes and lead to improvements in patient activity in future.

PMID- 29354411
TI  - Shoulder Arthroscopy in the Beach Chair Position.
AB  - Arthroscopic shoulder surgery can be performed in both the beach chair and
      lateral decubitus positions. The beach chair position is a reliable, safe, and
      effective position to perform nearly all types of shoulder arthroscopic
      procedures. The advantages of the beach chair position include the ease of setup,
      limited brachial plexus stress, increased glenohumeral and subacromial
      visualization, anesthesia flexibility, and the ability to easily convert to an
      open procedure. This position is most commonly used for rotator cuff repair,
      subacromial decompression, and superior labrum anterior-to-posterior repair
      procedures. To perform arthroscopy surgery in the beach chair position
      successfully, meticulous care during patient positioning and setup must be taken.
      In this Technical Note, we describe the necessary steps to safely and efficiently
      prepare patients in the beach chair position for arthroscopic shoulder surgery.

PMID- 29354412
TI  - Arthroscopic Anatomic Single-Bundle Anterior Cruciate Ligament Reconstruction
      Using Bone-Patellar Tendon-Bone Autograft: Pearls for an Accurate Reconstruction.
AB  - An anterior cruciate ligament (ACL) tear is one of the most common orthopaedic
      injuries. Optimal results are not always achieved after surgical reconstruction
      after a surgical technical error, namely, tunnel malposition. Understanding of
      the anatomy is vital, and several anatomic landmarks can be used to aid in an
      optimal reconstruction technique. The purpose of this Technical Note is to
      describe our preferred technique for an arthroscopic single-bundle anteromedial
      ACL reconstruction, using a bone-patellar tendon-bone autograft fixed with
      interference screws.

PMID- 29354413
TI  - Shoulder Arthroscopy in the Lateral Decubitus Position.
AB  - Arthroscopic shoulder surgery can be performed in both the beach chair and
      lateral decubitus positions. The lateral decubitus position allows for excellent
      exposure to all aspects of the glenohumeral joint and is therefore frequently
      employed in procedures such as stabilization, in which extensive visualization of
      the inferior and posterior aspects of the joint is required. Improved
      visualization is imparted due to applied lateral and axial traction on the
      operative arm, which increases the glenohumeral joint space. To perform
      arthroscopy surgery in the lateral decubitus position successfully, meticulous
      care during patient positioning and setup must be taken. In this Technical Note,
      we describe the steps required to safely, efficiently, and reproducibly perform
      arthroscopic shoulder surgery in the lateral decubitus position.

PMID- 29354414
TI  - A Femoral Tunnel View Test During ACL Reconstruction.
AB  - Despite technologic advances in the surgical techniques for anterior cruciate
      ligament (ACL) reconstruction, some patients continue to have violation of the
      femoral cortex, commonly referred to as wall blowout. These posterior or lateral
      cortical breaches lead to loss of graft containment and subsequent difficulty
      with graft fixation. If this intraoperative error is not promptly recognized and
      treated, the graft is at an increased risk of premature failure. Thus, in these
      situations, recognizing the complication and knowing strategies for alternative
      or salvage fixation are of importance. This article details a simple tunnel view
      test realized during ACL reconstruction that would enable determining the
      integrity and depth of the femoral tunnel. The femoral tunnel view test is a
      technically straightforward and quick test able to obtain a superior view of
      patient anatomy to facilitate accurate tunnel integrity evaluation during ACL
      reconstruction.

PMID- 29354415
TI  - Anterolateral Arthroscopic Posterior Subtalar Arthrodesis: The Surgical
      Technique.
AB  - The effectiveness of subtalar arthrodesis has been well documented in treating
      degenerative subtalar joint disease. The arthroscopic subtalar approach for
      arthrodesis has also been proved to give excellent results in terms of bone
      fusion rates and reduction of wound-related pain and complications. To date, the
      main concerns about arthroscopy have regarded incision-related neurologic
      complications such as lesions of the tibial, fibular, and sural nerves. In this
      context, we present a 2-portal lateral (anterior and middle) approach to
      arthroscopic subtalar arthrodesis, recently documented in the literature, that
      provides similar excellent access to the joint with a lower risk of nerve damage.

PMID- 29354416
TI  - Anterior Cruciate Ligament Reconstruction Basics: Bone-Patellar Tendon-Bone
      Autograft Harvest.
AB  - Anterior cruciate ligament reconstruction with bone-patellar tendon-bone
      autograft has long been considered the graft preference for young, active
      patients with anterior cruciate ligament injuries. The central-third of the
      native patellar tendon is a reliable graft and is the preferred option for
      competitive athletes given its excellent track record with high return-to-play
      rates and low failure rates. Disadvantages to using this graft include donor site
      morbidity and associated postoperative anterior knee pain, the risk of patellar
      fracture or patellar tendon tear, and the potential for graft-construct mismatch.
      In this Technical Note, we describe our preferred technique for bone-patellar
      tendon-bone autograft harvest and preparation for anterior cruciate ligament
      reconstruction.

PMID- 29354418
TI  - Elbow Ulnar Collateral Ligament Reconstruction Using a 4-Strand Docking Plus
      Technique.
AB  - The "Docking Plus" technique for elbow ulnar collateral ligament (UCL) surgery is
      described in the following text and video. Depite the general success of UCL
      surgery, significant rates of retear and failure of return to competition
      persist. Hypothesized reasons for UCL surgery failure include insufficient graft
      strength (midsubstance tears), insufficient graft tensioning (functional UCL
      insufficiency, valgus extension overload), and insufficient healing of graft to
      bone (proximal avulsions). This technique is meant to incorporate the best
      aspects of the previously described techniques for UCL reconstruction to create a
      larger, stronger, better-tensioned graft with a larger healing surface area to
      bone, a lower retear rate, and a lower risk of complications. The Docking Plus
      technique has been used since 2012.

PMID- 29354417
TI  - Arthroscopic Repair of Humeral Avulsion of the Glenohumeral Ligament Lesion.
AB  - Humeral avulsion of the glenohumeral ligament (HAGL) is a lesion associated with
      anterior shoulder instability. Although uncommon, HAGL lesions are a significant
      contributor to shoulder pain and dysfunction and, if missed, can even be a cause
      of failed Bankart repair. HAGL lesions should generally be repaired surgically;
      however, given their low prevalence, there is no consensus on the optimal
      surgical approach. The purpose of this Technical Note is to describe our
      preferred surgical technique for the fixation of an HAGL lesion using an all
      arthroscopic approach and a knotless suture anchor construct.

PMID- 29354419
TI  - Revisiting Fulkerson's Original Technique for Tibial Tubercle Transfer: Easing
      Technical Demand and Improving Versatility.
AB  - Tibial tubercle osteotomy is a well-described treatment option for a variety of
      patellofemoral disorders. Many techniques have evolved since its inception,
      including combinations of anteriorization, medialization, and distalization of
      the tibial tubercle. Although differing in their indications and end goal
      destination of the tubercle, these techniques share the challenging technical
      demands of achieving successful correction based off preoperative planning and
      prevention of intraoperative complications. We present our technique using
      osteotomy guide pins in a medial to lateral direction, originally described by
      Fulkerson in 1982. The advantages of our technique include better visualization
      for angle of osteotomy confirmation; versatility that provides options for any
      combination of anteriorization, medialization, or distalization; and the
      opportunity to maintain a distal cortical hinge if so desired.

PMID- 29354420
TI  - Lateral Meniscus Allograft Transplantation: The Bone Plug Technique.
AB  - Lateral meniscus tears are commonly encountered by orthopaedic surgeons. Despite
      efforts to repair and preserve the meniscus, meniscectomy is occasionally
      required to treat irreparable tears. The resulting lateral meniscus deficiency
      leads to increased tibiofemoral contact pressures and ultimately early
      osteoarthritic changes in the knee. Lateral meniscal allograft transplant (LMAT)
      has been proposed as a way to restore the lateral meniscus-deficient knee to its
      native form. Although several techniques for LMAT have been proposed, osseous
      fixation has demonstrated increased stability, improved outcomes, and improved
      long-term survival. This article presents a technique for LMAT using bone plugs
      and standard arthroscopic portals.

PMID- 29354421
TI  - Arthroscopic Inside-Out Repair of a Meniscus Bucket-Handle Tear Augmented With
      Bone Marrow Aspirate Concentrate.
AB  - Bucket-handle tears of the meniscus comprise nearly 10% of all meniscus tears and
      commonly affect the young male population. Displacement of the free segment can
      lead to significant pain and disability, necessitating reduction and surgical
      treatment. General contraindications include malalignment, severe arthritis,
      significant comorbidities, or chronic asymptomatic tears, but otherwise repair
      should almost always be performed. Options for surgical treatment include partial
      meniscectomy and arthroscopic repair using an all-inside, outside-in, or inside
      out technique. The purpose of this Technical Note is to detail our arthroscopic
      inside-out repair technique augmented with bone marrow aspirate concentrate.

PMID- 29354422
TI  - Combined Anatomic Anterior Cruciate Ligament and Double Bundle Anterolateral
      Ligament Reconstruction.
AB  - The results of arthroscopic anterior cruciate ligament (ACL) reconstruction are
      so far satisfactory and improving over time as a result of the improved
      understanding of the anatomy and biomechanics of the ACL. Rotational instability
      confirmed by a positive pivot shift is present in more than 15% of cases who
      underwent successful ACL reconstruction. Persistent rotational instability
      interferes with performing pivoting sports, and also may lead to meniscal and
      chondral injuries, or re-rupture of the reconstructed ACL. Surgeons reconsidered
      the anatomy and biomechanics of the ACL and introduced the double bundle ACL
      reconstruction technique aiming to achieve a more rotational control by
      reconstructing the anteromedial and anterolateral bundles of the ACL. To date,
      the results of double bundle ACL reconstruction are mixed and inconsistent. The
      improved understanding of the existence, function, and biomechanical role of the
      anterolateral ligament (ALL) in controlling the rotational instability of the
      knee has redirected and refocused attention on a supplemental extra-articular
      reconstruction of the ALL in conjunction with the intra-articular ACL
      reconstruction so as to restore normal kinematics of the knee. In this Technical
      Note, we describe a technique that allows for a combined ACL and double bundle
      ALL reconstruction using autogenous hamstring graft (semitendinosus and gracilis)
      tendons. This technique is an extension of our previously described technique of
      a combined anatomic ACL and single bundle ALL reconstruction. The improved
      understanding of the anatomy of the ALL makes a double bundle ALL reconstruction
      more anatomic than single bundle ALL reconstruction, as the native ALL is
      triangular or inverted Y in shape, with a narrow proximal femoral attachment and
      a broad distal tibial attachment between Gerdy's tubercle and the head of the
      fibula.

PMID- 29354423
TI  - Osteochondral Allograft Transplantation for Treatment of Medial Femoral Condyle
      Defect.
AB  - Chondral lesions of the knee can affect the young, active population, thereby
      causing severe morbidity and a large economic burden. Although numerous
      approaches have been described in the literature, restoration of hyaline
      cartilage has yet to be shown. Specifically, larger, full-thickness cartilage
      defects remain a challenge. This Technical Note details our technique for
      biologic unicompartmental osteochondral allograft transplantation for the
      treatment of large femoral condyle articular cartilage defects.

PMID- 29354424
TI  - The "Purse String" Procedure for Recurrent Anterior Glenohumeral Instability: A
      Simple Technique to Achieve Bankart Repair, Capsular Shift, and a Good Labral
      Bumper.
AB  - Failure of arthroscopic techniques in cases of recurrent anterior glenohumeral
      instability may result from inadequate treatment of capsular injury. The use of
      few anchors has been cited as a cause of failure in arthroscopic stabilization
      techniques. This applies to the use of the suture anchors as spot-welding points
      in conventional techniques. It has been shown that horizontal mattress suture
      techniques restore better labral height and anatomy than simple suture techniques
      in the repair of acute Bankart lesions. Horizontal mattress repairs, like the one
      achieved with the "purse-string" technique, pushes the labrum toward the humeral
      side of the joint, thus providing a buttress to the glenohumeral joint. We
      present the purse-string technique, which involves the use of only 1 suture
      anchor located at the 4-o'clock position. Sutures are passed through the labrum
      and capsule from south to north, thus allowing the incorporation of more capsular
      tissue involved in the raising of the anterior labral bumper. One suture anchor
      at the 4-o'clock position is used to ensure a purse-string effect, with
      tightening of the capsule in the inferosuperior plane and repair of the Bankart
      lesion. The repair achieved is 3-fold: Bankart repair, south-to-north capsular
      shift, and creation of an anterior bumper.

PMID- 29354427
TI  - Simplifying Anterior Cruciate Ligament Graft Bone Plug Reconstructions: The "U"
      Trough Technique.
AB  - This Technical Note discusses an anterior cruciate ligament graft preparation
      technique to simplify and ease graft visualization, insertion, and fixation. Our
      technique incorporates a 2-mm central trough in the bone plug of the graft to
      improve one's ability to efficiently identify and orient the anterior cruciate
      ligament graft during insertion, and ensure correct screw placement and fixation.

PMID- 29354425
TI  - Autogenous Hamstring-Bone Graft Preparation for Anterior Cruciate Ligament
      Reconstruction.
AB  - Despite the popularity of anterior cruciate ligament (ACL) reconstruction
      procedures, the ideal graft for reconstruction remains a matter of controversy.
      The ideal graft for ACL reconstruction should have histologic and biomechanical
      characteristics similar to those of the native ACL; should be quickly and fully
      incorporated within the bony tunnels; should maintain its viscoelastic properties
      for a long time; should have minimal donor-site morbidity; should be of
      sufficient length and diameter; should have minimal adverse effects on the
      extensor mechanism; should have no risk of rejection or disease transmission; and
      should be cost-effective and readily available. Synthetic grafts are not widely
      accepted because of their dangerous complications. The main sources of grafts for
      ACL reconstruction are allografts and autografts. Each type of graft has its own
      relative advantages and disadvantages. Allografts are not available in every
      country, besides being expensive, and there are many concerns regarding disease
      transmission. Autografts, particularly bone-patellar tendon-bone (BPTB), and
      hamstring tendon grafts have been the standard for ACL reconstruction. The main
      advantage of autogenous BPTB grafts is the direct bone-to-bone healing in the
      tunnel, whereas the main disadvantages of such grafts are related to donor-site
      morbidity, anterior knee pain, and extensor mechanism dysfunction. The popularity
      of autogenous hamstring tendon grafts for ACL reconstruction is increasing, but
      there are still concerns regarding the slow soft tissue-to-bone healing, with
      delayed healing and incorporation of the graft. We describe a technique for ACL
      reconstruction with autogenous hamstring-bone graft, aiming to produce a type of
      graft that combines the main advantages of BPTB and hamstring grafts, with
      avoidance of the main disadvantages of these 2 most commonly used graft types in
      ACL reconstruction.

PMID- 29354426
TI  - Acromioclavicular Joint Dislocation: Repair Through Open Ligament Transfer and
      Nonabsorbable Suture Fixation.
AB  - Acromioclavicular (AC) joint instability is a fairly common and particularly
      limiting injury that may result in persistent pain and reduced quality of life.
      In most cases, conservative management is successful. However, in the case of a
      severe AC joint dislocation, surgical intervention may be warranted. Previous
      surgical techniques for treatment of AC joint instability include screw fixation
      between the coracoid and clavicle, coracoacromial ligament transfer from its
      acromial insertion to the clavicle, and reconstruction of the coracoacromial
      and/or coracoclavicular ligaments. The purpose of this Technical Note is to
      describe our preferred technique for the treatment of a high-grade AC dislocation
      through coracoacromial ligament transfer to the lateral clavicle and
      nonabsorbable suture fixation between the coracoid process and clavicle.

PMID- 29354428
TI  - Tibial Eminence Fracture Repair With Double Hewson Suture Passer Technique.
AB  - Displaced tibial eminence fractures are commonly encountered in pediatric
      patients and are often considered to be functionally equivalent to an anterior
      cruciate ligament (ACL) rupture. While a variety of techniques are available for
      fixation of this injury, we describe an anchorless technique relying on suture
      fixation tied over a bone bridge. This technique also relies on two intra
      articular Hewson suture passers to quickly and effectively pass and shuttle
      sutures through the ACL and tibial bone tunnels in order to reduce and fix the
      fracture fragment. We also briefly review various types of fixation used for
      tibial eminence fractures.

PMID- 29354429
TI  - Mini-open Incision Sports Hernia Repair: A Surgical Technique for Core Muscle
      Injury.
AB  - One cause of groin pain in highly active patients may be a core muscle injury,
      commonly referred to as sports hernia. When patients fail nonoperative
      management, there are a number of surgical options that may be pursued.
      Typically, they will involve the direct repair of the rectus abdominis back to
      the pubis. However, we believe that this repair can be further strengthened by
      the appropriate lengthening of the adductor longus from the conjoined tendon.
      Therefore, we present a surgical technique that involves both rectus abdominis
      repair and adductor longus lengthening in those who show a core muscle injury
      that is refractory to conservative management. We believe that this technique can
      be easily replicated by practitioners reading this Technical Note.

PMID- 29354430
TI  - Identifying and Exposing the Proximal Biceps in Its Groove: The "Slit" Technique.
AB  - Proximal biceps tendon pathology is a common source of shoulder symptoms. Thus,
      visualization of the entire extent of the biceps tendon is often required for
      both diagnostic and therapeutic purposes. Accurately recognizing the presence and
      extent of biceps pathology intraoperatively is made more difficult, however, due
      to the extra-articular location of a significant portion of the biceps tendon as
      it courses within the bicipital groove. Unfortunately, identification of the
      biceps groove in the subacromial space is often challenging due to the lack of
      visual and tactile landmarks. A technique that facilitates efficient and reliable
      bicipital groove identification and biceps tendon visualization along its entire
      course within the groove is presented.

PMID- 29354431
TI  - Anterior Cruciate Ligament Tunnel Placement Using the Pathfinder Guide.
AB  - Reconstruction techniques for the anterior cruciate ligament (ACL) have evolved
      considerably over the past 3 decades. The femoral tunnel is most commonly made
      via a transtibial or separate anteromedial portal approach. Benefits and
      drawbacks for each of these techniques exist. Improper tunnel placement is the
      cause of failure for ACL reconstruction 70% of the time. We present a hybrid
      technique for femoral tunnel placement using the Pathfinder ACL guide, which
      attempts to give the surgeon many of the benefits of both the transtibial and
      anteromedial portal techniques without the drawbacks.

PMID- 29354433
TI  - Stump Incorporation for Anterior Cruciate Ligament Reconstruction: A Step Towards
      a More Anatomical Reconstruction.
AB  - In most anterior cruciate ligament (ACL) tears, the tear is at the femoral side
      leaving a robust stump attached to the tibia. Stump-preserving ACL reconstruction
      carries the advantage of rapid reinnervation and revascularization of the graft.
      In this technique, the femoral tunnel is created after exposing the femoral
      footprint. The ACL tibial stump is split and the tip of the ACL tibial guide is
      introduced through this split to reach the center of the tibial footprint. The
      tibial tunnel is then created and the ACL stump is bored to allow the passage of
      the graft. After the passage of the graft inside the stump and femoral and tibial
      fixation, 1 or 2 sutures are used to suture the graft to the stump by a suture
      passing device (Expressew II; Depuy Mitek, Raynham, MA). This technique, in
      addition to preservation of the mechanoreceptors and vascular channels for
      revascularization and reinnervation of the graft, allows preservation of the
      shape and surface area of the wide tibial origin of the ACL.

PMID- 29354432
TI  - Two-Stage Revision Anterior Cruciate Ligament Reconstruction Using Allograft Bone
      Dowels.
AB  - Revision anterior cruciate ligament (ACL) reconstruction is substantially more
      challenging than primary reconstruction. Management of previously malpositioned
      or widened tunnels often requires innovative approaches for managing bony
      defects. Massive osteolysis with poor bone stock and convergence or overlapping
      of revision tunnels into the previously placed tunnels may necessitate a staged
      revision procedure. In this surgical technique description, we describe a method
      for the management of bony deficiencies using allograft bone dowels in staged
      revision ACL reconstruction.

PMID- 29354434
TI  - ACL Reconstruction Basics: Quadruple (4-Strand) Hamstring Autograft Harvest.
AB  - Hamstring tendon autograft remains a popular graft choice for anterior cruciate
      ligament (ACL) reconstruction. Although there are a variety of autograft and
      allograft options available for ACL reconstruction, advantages of hamstring
      tendon autografts include decreased postoperative knee pain and an overall easier
      surgical recovery compared with bone patellar tendon bone autograft. In addition,
      4-stranded (quadruple) hamstring grafts are among the strongest grafts
      biomechanically (at time equals zero). Although the technique of hamstring
      autograft harvest is relatively straightforward, it is critical to pay attention
      to several technical steps to avoid iatrogenic neurovascular damage as well as to
      avoid premature amputation of the graft while using a tendon stripper. In this
      Technical Note, we describe a technique of hamstring autograft harvest for ACL
      reconstruction for a quadruple (4-strand) hamstring graft using the gracilis and
      semitendinosus tendons.

PMID- 29354435
TI  - Inside-Out Repair of Meniscal Ramp Lesions.
AB  - Meniscal ramp lesions have been reported to be present in 9% to 17% of patients
      undergoing anterior cruciate ligament reconstruction. Detection at the time of
      arthroscopy can be accomplished based upon clinical suspicion and careful
      evaluation without the use of an accessory posteromedial portal. Options for
      surgical treatment include arthroscopic repair using an all-inside or inside-out
      technique. The purpose of this Technical Note is to detail our arthroscopic
      inside-out repair technique for meniscal ramp lesions.

PMID- 29354436
TI  - Horizontal Cleavage Meniscus Tear Treated With All-inside Circumferential
      Compression Stitches.
AB  - Horizontal cleavage meniscus tears are a common orthopedic injury often treated
      with partial or total meniscectomy versus repair. This Technical Note presents a
      technique for all-inside repair with uniform compression of the superior and
      inferior leaflets by placement of multiple circumferential compression stitches
      using an all-inside self-retrieving suture passing device. The currently
      described technique provides several advantages for all-inside repair of a
      horizontal cleavage tear: (1) eliminates the need for a posterior incision, (2)
      minimizes the risk of neurovascular injury, (3) uses standard arthroscopy portals
      (or small modifications), and (4) requires only a single suture deployment with a
      self-retrieving device for each circumferential compression stitch. The resulting
      circumferential stitch provides uniform compression to the superior and inferior
      leaflets, promoting meniscal healing. This configuration has been shown to have
      the highest load to failure of all repair patterns.

PMID- 29354437
TI  - Augmentation of the Pullout Repair of a Medial Meniscus Posterior Root Tear by
      Arthroscopic Centralization.
AB  - The meniscus roots are critical for meniscus function in preserving correct knee
      kinematics and avoiding meniscus extrusion and, consequently, in the progression
      of osteoarthritis. Several techniques exist for medial meniscus posterior root
      tear repair; however, current surgical techniques have been proved to fail to
      reduce meniscus extrusion, which has been shown to be associated with development
      of osteoarthritis, although significant improvements in the postoperative
      clinical findings have been achieved. This Technical Note describes an
      arthroscopic technique for the medial meniscus posterior root tear in which a
      pullout repair is augmented by a centralization technique to restore and maintain
      the medial meniscus function by efficiently reducing meniscus extrusion.

PMID- 29354438
TI  - Osteotomy of the Tibial Tubercle for Anteromedialization.
AB  - Patellofemoral instability is a common cause of anterior knee pain, especially in
      younger and more active patients. Treatment of instability varies considerably
      depending on the patient's symptoms as well as the cause of the instability.
      Lateral instability has a particularly broad spectrum of treatment algorithms
      including patellar taping, arthroscopy, lateral release, medial patellofemoral
      ligament (MPFL) reconstruction, MPFL repair, and osteotomy of the tibial tubercle
      for realignment. Acute traumatic lateral dislocation is commonly associated with
      a tear of the MPFL and, therefore, needs to be addressed. However, patients who
      show lateralization of the tibial tubercle with an increased tibial tubercle-to
      trochlear groove distance, tibial tubercle-to-posterior cruciate ligament
      distance, and Q-angle measurements often display chronic instability even after
      an MPFL reconstruction. In these cases, an osteotomy of the tibial tubercle is
      required to establish proper alignment and minimize the risk of recurrence of
      instability. The objective of this Technical Note is to describe our preferred
      method to complete a Fulkerson tibial tubercle osteotomy for anteromedialization
      and treatment of chronic patellar instability.

PMID- 29354439
TI  - Pectoralis Major Transfer for Treatment of Serratus Anterior Dysfunction in the
      Setting of Long Thoracic Nerve Palsy.
AB  - Symptomatic scapular winging resulting in scapular dyskinesia leads to a wide
      spectrum of clinical complaints, most notably periscapular pain. The
      malpositioning of the scapula, termed through use of the acronym SICK (scapular
      malposition, inferior-medial border prominence, coracoid pain and malposition,
      and dyskinesia of scapular movement), is due to the irregular activity of one or
      more of the periscapular muscles. In particular, the serratus anterior,
      innervated by the long thoracic nerve, is a key muscle that stabilizes the
      scapula and provides coordinated scapulohumeral rhythm. If the long thoracic
      nerve is injured, this results in significant shoulder dysfunction and scapular
      winging that may require surgical intervention. The purpose of this Technical
      Note is to present our preferred technique to treat symptomatic scapular winging
      due to long thoracic nerve palsy through transfer of the pectoralis major with
      its bone insertion to the inferior edge of the scapula.

PMID- 29354440
TI  - Sternoclavicular Joint Reconstruction in the Setting of Medial Comminuted
      Clavicle Fracture.
AB  - A dislocation of the sternoclavicular joint is a particularly threatening injury
      given the close proximity of neighboring vital structures. Moreover, a traumatic
      injury resulting in a comminuted fracture of the medial clavicle in addition to
      joint instability results in even greater complexity. In the setting of
      sternoclavicular joint instability, definitive treatment that will lead to
      complete resolution of symptoms is necessary. Various treatment methods, both
      conservative and operative, with positive treatment outcomes have been described.
      The aim of this Technical Note is to describe our preferred surgical technique to
      treat a medial comminuted clavicle fracture with anterior sternoclavicular joint
      instability.

PMID- 29354441
TI  - Arthroscopic Excision of an Osteoid Osteoma of the Lesser Trochanter of the
      Femoral Neck.
AB  - Osteoid osteoma frequently requires surgical treatment, especially among young,
      active patients. However, surgeons are reluctant to perform open surgery for an
      osteoid osteoma of the femoral neck area because the conventional surgical
      approach requires a large incision in muscular patients, and percutaneous
      resection with a trephine has the attendant risk of subsequent fracture.
      Recently, arthroscopic excision of an osteoid osteoma has been reported as a less
      invasive, safer procedure than traditional open curettage. Hip arthroscopy using
      the burr-down technique under C-arm guidance to locate and remove the lesion of
      the femur neck has also shown promise. The presented technique minimizes muscle
      damage around the femur and enables surgeons to confirm complete resection of the
      lesion through direct, detailed visualization. Furthermore, early return to
      previous activity can be achieved after excising the lesion located at the calcar
      femorale, which is an area with a heavy weight-bearing load. The objective of
      this Technical Note was to describe our preferred technique for the surgical
      excision of osteoid osteoma located at the base of the femoral neck through the
      use of arthroscopy.

PMID- 29354442
TI  - Open Repair of an Anterior Humeral Avulsion of the Glenohumeral Ligament.
AB  - A humeral avulsion of the glenohumeral ligament, or HAGL lesion, is an uncommon
      yet disabling shoulder injury, which leads to complaints of pain and overall
      inability to properly use the shoulder from patients. The diagnosis of a HAGL
      lesion is particularly challenging. To arrive at an accurate diagnosis, the use
      of a magnetic resonance arthrogram is suggested along with high clinical
      suspicion. A HAGL lesion may be anterior or posterior. This difference dictates
      the type of surgical treatment to be undertaken. Although a posterior HAGL lesion
      is repaired arthroscopically, an anterior HAGL lesion is treated through an open
      approach. The purpose of this Technical Note is to describe our preferred
      technique to surgically treat an anterior HAGL lesion through an open approach.

PMID- 29354443
TI  - Endoscopic Curettage of Bone Cyst of the Fibular Head.
AB  - Open resection of cystic or other benign intramedullary lesions of the fibular
      head and neck requires dissection and mobilization of the common peroneal nerve.
      The purpose of this Technical Note is to describe a minimally invasive approach
      of fibular head bone endoscopy for resection of a bone cyst or other benign
      intramedullary lesions of the fibular head and neck. The common peroneal nerve,
      biceps femoris tendon, and lateral collateral ligament are preserved.

PMID- 29354444
TI  - Meniscal Ramp Lesion Repair by a Trans-septal Portal Technique.
AB  - The identification of meniscal ramp lesions can be quite difficult or even
      impossible with conventional anterior arthroscopic viewing and working portals.
      Although even the use of transnotch viewing maneuvers into the posteromedial
      compartment increases the likelihood of diagnosis, it is the posteromedial and
      trans-septal portals that provide the best direct visualization of these many
      times "hidden lesions." In this surgical technique description, we describe a
      method to not only adequately visualize the ramp lesion, but also provide subtle
      variations to existing surgical techniques that can help limit injury to
      neurovascular structures as well as gain satisfactory vertical suture repair of
      this posteromedial meniscocapsular injury.

PMID- 29354445
TI  - Arthroscopic Saucerization and All-Inside Repair of a Delaminated Discoid Lateral
      Meniscus.
AB  - Preservation of the meniscus has been shown to influence the progression of
      degenerative changes of the knee. As more meniscus is preserved, the propensity
      for development of osteoarthritis is lessened. Surgical treatment of a torn
      discoid meniscus has typically been a subtotal meniscectomy or partial
      meniscectomy. Similar to tears of a normal meniscus, partial meniscectomy
      compared with subtotal meniscectomy of the discoid meniscus confers better long
      term results. With the abnormal morphology predisposing the discoid meniscus to
      tearing, several characteristic tear patterns can be observed-the horizontal tear
      being commonly encountered. We present a technique that not only creates a more
      normal morphology of a discoid meniscus but also preserves the tissue by using an
      all-inside, intrameniscal repair technique. This technique restores the central
      rim of the meniscus in the setting of a horizontal cleavage plane, thus restoring
      a more normal meniscus morphology.

PMID- 29354446
TI  - Multiple Osteochondral Allograft Transplantation with Concomitant Tibial Tubercle
      Osteotomy for Multifocal Chondral Disease of the Knee.
AB  - Symptomatic patellofemoral chondral lesions are a challenging clinical entity, as
      these defects may result from persistent lateral patellar maltracking or
      repetitive microtrauma. Anteromedializing tibial tubercle osteotomy has been
      shown to be an effective strategy for primary and adjunctive treatment of focal
      or diffuse patellofemoral disease to improve the biomechanical loading
      environment. Similarly, osteochondral allograft transplantation has proven
      efficacy in physiologically young, high-demand patients with condylar or
      patellofemoral lesions, particularly without early arthritic progression. The
      authors present the surgical management of a young athlete with symptomatic
      tricompartmental focal chondral defects with fresh osteochondral allograft
      transplantation and anteromedializing tibial tubercle osteotomy.

PMID- 29354447
TI  - Arthroscopic Superior Capsule Reconstruction Technique in the Setting of a
      Massive, Irreparable Rotator Cuff Tear.
AB  - Massive, irreparable rotator cuff tears are challenging to treat and associated
      with pain and severe limitation in shoulder elevation due to the proximal
      migration of the humeral head and, consequently, subacromial impingement.
      Furthermore, retraction of the tendons in combination with fat infiltration and
      muscular weakness results in unpredictable treatment outcomes. While conservative
      treatment may be warranted for low-demand patients, surgical treatment is often
      indicated for a successful return to activities of daily living as well as an
      improved quality of life. The reported failure rate of rotator cuff repair for
      the treatment of a massive rotator cuff tear varies. However, this failure is
      often found at the interface between the tendon and tendon footprint. Several
      techniques have been reported to address this pathology, including muscular
      transfer, arthroscopic debridement, augmentation procedures, and superior capsule
      reconstruction. In particular, superior capsule reconstruction has been reported
      as a safe and effective method to treat a massive, irreparable rotator cuff tear.
      The purpose of this Technical Note is to describe our preferred technique of a
      superior capsule reconstruction for the treatment of a massive, irreparable
      rotator cuff tear.

PMID- 29354448
TI  - Femoral Derotation Osteotomy Technique for Excessive Femoral Anteversion.
AB  - Excessive femoral anteversion may lead to increasing stress placed on the
      anterior acetabulum and soft tissues, which can predispose to intra-articular hip
      pathology. By addressing the excessive femoral anteversion in combination with
      intra-articular hip pathology, the results will be durable over time. This
      technique details how to perform a femoral derotation osteotomy for excessive
      femoral anteversion after addressing intra-articular pathology with hip
      arthroscopy in one surgical intervention. This allows the surgeon to address both
      the underlying pathoanatomy and the resultant intra-articular sequelae.

PMID- 29354449
TI  - An Inexpensive Support for Prone or Lateral Decubitus Elbow Arthroscopy and Open
      Elbow Surgery.
AB  - An inexpensive and radiolucent elbow can be built with a PVC pipe available at
      any home center or hardware store for less than $25 that allows elbow arthroscopy
      or open elbow surgery such as open reductions and internal fixation to be
      performed in the prone, "sloppy" lateral, or decubitus position.

PMID- 29354450
TI  - Subpectoral Biceps Tenodesis: Interference Screw and Cortical Button Fixation.
AB  - Bicep tendon pathology often arises from chronic overuse injuries, acute trauma,
      or degenerative changes in the glenohumeral joint. These injuries can cause
      significant shoulder pain, and can greatly limit range of motion and, in turn,
      activities of daily living. The diagnosis of biceps pathologies can be
      challenging, because patients often present with nonspecific symptoms. Some bicep
      tendon pathologies may be treated nonoperatively; however, biceps tendon
      subluxation and the presence of rotator cuff or SLAP lesions require surgical
      management. One of the options for the treatment of bicep tendon pathology
      includes miniopen subpectoral biceps tenodesis. The purpose of this Technical
      Note is to describe in detail our preferred operative technique for miniopen
      subpectoral biceps tenodesis with 2 different fixation methods.

PMID- 29354451
TI  - Arthroscopic Iliopsoas Release at the Level of the Lesser Trochanter Following
      Total Hip Arthroplasty.
AB  - Iliopsoas impingement is an uncommon cause of pain after total hip arthroplasty.
      If pain persists after a trial of conservative treatment, surgical intervention
      can alleviate the patient's symptoms. Multiple advantages exist to release the
      iliopsoas tendon at the level of the lesser trochanter. The purpose of this
      Technical Note is to demonstrate a technique for arthroscopic release of the
      iliopsoas tendon at the lesser trochanter after total hip arthroplasty.

PMID- 29354452
TI  - Arthroscopic Proximal Row Carpectomy Using the Volar Central Portal.
AB  - Proximal row carpectomy (PRC) is a well-accepted procedure for the treatment of
      degenerative lesions of the wrist and advance Kienbock disease. This procedure
      has been classically described as an open procedure but recently has been
      reported as an arthroscopic one. Arthroscopic PRC has several advantages such as
      minimal damage to the dorsal and volar ligaments as well as there being no need
      to detach the capsule, which can facilitate earlier mobilization and can decrease
      postoperative stiffness. In addition, there is a reduced risk of the interosseous
      posterior nerve being injured, and the proprioception system continues to
      function. This arthroscopically assisted technique uses the volar central portal
      as a third portal, which can be useful to remove the volar portions of the bones
      to view the dorsal areas of the bones and to allow the surgeon to work with 2
      instruments at the same time. As a result, the time spent on the procedure can be
      reduced.

PMID- 29354453
TI  - Arthroscopic Medial Meniscus Posterior Root Reconstruction Using Auto-Gracilis
      Tendon.
AB  - There have been several techniques to repair the medial meniscus posterior root
      tears (MMPRTs) with the goal of restoring the anatomic and firm fixation of the
      meniscal root to bone. Many anatomic studies about the menisci also have been
      developed, so a better understanding of the anatomy could help surgeons perform
      correct fixation of the MMPRTs. The meniscal roots have ligament-like structures
      that firmly attach the menisci to the tibial plateau, and this structural concept
      is important to restore normal biomechanics after anatomic root repair. We
      present arthroscopic transtibial medial meniscus posterior root reconstruction
      using auto-gracilis tendon.

PMID- 29354454
TI  - Arthroscopic Medial Meniscal Allograft Transplantation with Modified Bone Plug
      Technique.
AB  - The meniscal allograft transplantation (MAT) has been reported to be an effective
      treatment in terms of pain relief and functional improvement in symptomatic
      meniscus-deficient knee. The medial MAT is usually performed with the bone plug
      technique or soft tissue fixation for root fixation. We describe medial MAT with
      modified bone plug technique that permits easy passage of posterior bone plugs
      and facilitates bone-to-bone healing. With this method, an anterior bone plug
      with a long cylindrical shape is prepared, and the posterior bone plug is
      prepared with a flat bone shell containing a cancellous portion. This modified
      technique facilitates graft passage as well as bone-to-bone healing.

PMID- 29354455
TI  - Fresh Osteochondral Allograft Transplantation for Focal Chondral Defect of the
      Humerus Associated With Anchor Arthropathy and Failed SLAP Repair.
AB  - Isolated, full-thickness articular cartilage lesions of the glenohumeral joint
      can cause pain, mechanical symptoms, and impaired function. Reports on operative
      management of these injuries with arthroscopic techniques, such as marrow
      stimulation, have shown improvement in patient symptoms. In cases where the
      subchondral bone is involved, osteochondral allograft (OCA) transplantation has
      shown positive results for contained, focal cartilage defects. The technique for
      OCA transplantation to treat Hill-Sachs lesions has been reported in detail, and
      there are multiple case series reporting on the outcomes of OCA used for this
      purpose. This Technical Note shows the application of OCA to treat a case of
      anchor arthropathy where a glenoid anchor placed during arthroscopic
      stabilization causes iatrogenic damage to the humeral head. This type of injury
      can result in cartilage lesions in uncommon locations, such as on the posterior
      humeral head. In this description, the technical pearls and pitfalls of managing
      difficult-to-access posterior humeral head lesions are presented along with the
      senior authors' general technique for OCA to treat focal lesions of the humeral
      head cartilage.

PMID- 29354456
TI  - Endoscopic Anterior Subcutaneous Transposition of the Ulnar Nerve.
AB  - Cubital tunnel syndrome refers to ulnar nerve compressive neuropathy and most
      commonly occurs at the level of the elbow. Surgical options include in situ
      decompression, decompression with anterior transposition of the ulnar nerve, and
      medial epicondylectomy with or without decompression. With the advancement of
      endoscopic surgery, techniques of endoscopic in situ decompression of the ulnar
      nerve, endoscopy-assisted anterior transposition, and endoscopic anterior
      transposition of the ulnar nerve have been reported with the advantage of
      minimally invasive surgery. We describe a 2-portal technique of endoscopy
      assisted anterior subcutaneous transposition of the ulnar nerve.

PMID- 29354457
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1016/j.eats.2017.02.014.].

PMID- 29354458
TI  - Endoscopic Ganglionectomy of Palmar Ganglion via Flexor Carpi Radialis
      Tendoscopy.
AB  - Palmar ganglion is rare. Deep palmar ganglion usually arises from the wrist joint
      and may cause compression neuropathy. Superficial palmar ganglion may arise from
      the flexor tendons of the wrist. The chance of compression neuropathy is expected
      to be less than deep palmar ganglion. However, there is a higher chance of
      perforation through the skin and the ganglion may affect hand grip. Open
      resection of the ganglion does not require extensive deep soft tissue dissection.
      However, the skin incision can still be extensile to trace the stalk to the
      tendon of origin. The purpose of this Technical Note is to report the details of
      endoscopic ganglionectomy for superficial palmar ganglion arising from the flexor
      carpi radialis tendon.

PMID- 29354459
TI  - Arthroscopic Posterior Cruciate Ligament Reconstruction With Remnant Preservation
      Using a Posterior Trans-septal Portal.
AB  - We describe a surgical technique for arthroscopic posterior cruciate ligament
      (PCL) reconstruction with remnant preservation of the original PCL fibers using a
      posterior trans-septal portal approach. Using the transtibial technique and the
      posterior trans-septal portal approach allows good visualization of the tibial
      tunnel preparation, easy access to the tibial tunnel without neurovascular
      injury, and preservation of remnant PCL fibers. In the preparation of the tibial
      tunnel, we expose the PCL tibial attachment site completely, detach the posterior
      capsule from the PCL, and preserve the distal stump of the PCL without
      neurovascular injury. PCL reconstruction is performed in a way that preserves the
      remnant PCL fibers. We report on our surgical technique for arthroscopic PCL
      reconstruction preserving the original PCL fibers.

PMID- 29354460
TI  - Reconstruction of the Medial Patellofemoral Ligament.
AB  - Patellar instability has been shown to be associated with different major
      factors. However, studies have demonstrated that soft tissue reconstructions are
      adequate enough to reestablish patellar constraint. In recent years, the medial
      patellofemoral ligament has been recognized as the primary passive restraint for
      lateral translation of the patella. Their reconstruction has gain popularity as
      the procedure is quite simple and fast. Although several surgical techniques have
      been described for their reconstruction, no clear consensus has been reached as
      to which is best. We present an implant-free, medial patellofemoral ligament
      reconstruction technique that uses a gracilis tendon autograft, 2 bone convergent
      tunnels at the original patellar attachment, and looping the graft around the
      adductor magnus tendon that is used as a pulley for femoral fixation.

PMID- 29354461
TI  - Endoscopic Ganglionectomy of the Volar Radial Wrist Ganglion.
AB  - Volar ganglion cyst of the wrist is a common hand problem faced by orthopaedic
      surgeons. Excision is indicated if it is painful. Arthroscopic ganglionectomy of
      the wrist ganglion has been reported with the advantage of minimally invasive
      surgery. Most of them involve elimination of the valvular mechanism and internal
      drainage of the ganglion fluid to the wrist joint. The access of the ganglion sac
      is limited especially for a multiloculated cyst. The purpose of this Technical
      Note is to report the technique of endoscopic resection of the volar radial wrist
      ganglion. This can ensure complete resection of the ganglion sac especially for
      the multiloculated one.

PMID- 29354462
TI  - Arthroscopic Arthrodesis of the First Metatarsophalangeal Joint in Hallux Valgus
      Deformity.
AB  - Arthrodesis of the first metatarsophalangeal joint is indicated for hallux valgus
      associated with degenerative changes, severe deformity, or rheumatoid arthritis
      and those for whom primary hallux valgus surgery has failed. Open approach
      requires extensive soft tissue dissection. The purpose of this Technical Note was
      to report the details of arthroscopic arthrodesis of the first
      metatarsophalangeal joint in severe and rigid hallux valgus deformity. This is a
      combination of endoscopic lateral release of the first metatarsophalangeal joint
      and arthroscopic arthrodesis of the joint. Endoscopic lateral release will
      convert the deformity into a flexible one and facilitate a subsequent arthrodesis
      procedure.

PMID- 29354463
TI  - Endoscopic Resection of Peroneal Tubercle.
AB  - Symptomatic hypertrophy of the peroneal tubercle can result in pain, clicking
      sensation, and limitation of ambulation. Surgical resection is indicated for
      symptomatic hypertrophied tubercle that is recalcitrant to conservative
      treatment. The purpose of this Technical Note is to report the details of
      tendoscopic resection of the hypertrophied peroneal tubercle. This is performed
      through zone 2 peroneus longus tendoscopy. Any associated hindfoot deformity and
      peroneal tendon pathology should also be addressed.

PMID- 29354464
TI  - Arthroscopic Arthrodesis of the Lesser Ray Tarsometatarsal Joints: 2-Portal
      Technique.
AB  - Tarsometatarsal (Lisfranc) destruction of the tarsometatarsal articulation of the
      lesser rays is most commonly due to midfoot Charcot neuroarthropathy.
      Tarsometatarsal arthrodesis is indicated when conservative management cannot
      relieve the symptoms. The purpose of this Technical Note is to describe a
      minimally invasive approach of arthroscopic arthrodesis of the destructed lesser
      ray tarsometatarsal joints. The arthroscopic procedure is performed through the
      lateral and P1-2 Lisfranc portals. It has the advantages of better cosmesis, less
      wound complication, less bone resection, and more thorough joint debridement.
      However, it is contraindicated if there is associated significant foot deformity
      or shortening of the lesser foot rays.

PMID- 29354465
TI  - Arthroscopic-Assisted Pectoralis Minor Transfer for Irreparable Tears of the
      Upper Two-thirds of the Subscapularis Tendon: Surgical Technique.
AB  - Open transfer of the pectoralis minor through a deltopectoral approach has been
      described to treat irreparable tears of the upper two-thirds of the
      subscapularis. We present a less invasive arthroscopic-assisted technique for
      this transfer. Atraumatic dissection of the pectoralis minor and harvesting of
      the tendon with a bone chip from the coracoid process allow strong fixation with
      a double-button device on the lesser tuberosity. This arthroscopic technique
      allows assessment and treatment of associated intra- or extra-articular lesions
      and represents a promising option for the management of irreparable tears of the
      subscapularis.

PMID- 29354466
TI  - Intra-articular Anterior Cruciate Ligament Reconstruction With Extra-articular
      Lateral Tenodesis of the Iliotibial Band.
AB  - An increasing concern has been given to the rotation stability of the knee in the
      setting of an anterior cruciate ligament (ACL) reconstruction. This growing
      interest stems from a better understanding of the rotational stability of the
      knee afforded by the identification of the anterolateral ligament. Previously, a
      residual abnormal pivot-shift test had been found after an anatomic single-band
      reconstruction of the ACL because of a lack of rotational stability, which may
      lead to the development of osteoarthritis. Residual instability affects function,
      especially in high-demand athletes who perform many flexion-rotation movements
      during sporting activity. The purpose of this Technical Note is to describe our
      preferred method of intra-articular ACL reconstruction using a hamstring tendon
      autograft in combination with an extra-articular iliotibial band tenodesis for
      reinforcement of rotational stability.

PMID- 29354467
TI  - Posterior "Double Cannular Sliding Technique" for Resection of Posterior Septum
      of the Knee Joint.
AB  - We introduce the posterior double cannular sliding technique, which is an easy,
      fast, safe, and reproducible method for posterior septum resection of the knee
      joint. Several posterior compartment procedures have been developed. Procedures
      with anterior-posterior approaches (transnotch approach) and posterior-posterior
      approaches have become possible for arthroscopic total synovectomy and loose body
      removal. For resection of the posterior septum with posterior-posterior
      approaches, several authors have used various methods. However, although previous
      studies reported posterior septum resection in the posterior portal, or
      perforation of the posterior septum by blind vision or transnotch approach,
      specific postperforation techniques to resect the posterior septum have not been
      reported. Furthermore, methods of posterior septum resection remain difficult to
      perform using posterior portal arthroscopy, with difficulties in the approach and
      in achieving reproducible outcomes. Thus, we introduce the posterior double
      cannular sliding technique, which is a reproducible method that uses 2
      transparent cannulas and a switching stick under direct visualization control
      with a transnotch approach, thereby minimizing the risk of potential
      neurovascular or posterior cruciate ligament injury for all procedures in
      posterior septum resection.

PMID- 29354468
TI  - Imaging of Abductor Tears: Stepwise Technique for Accurate Diagnosis.
AB  - This article presents the authors' technique for evaluation of possible abductor
      tears with magnetic resonance imaging (MRI). By using T2 fat-saturated coronal
      and axial slices of the hip and T1 coronal images of the pelvis, the authors show
      how to visualize all tears of the abductor tendons and signs of chronic abductor
      deficiency. After diagnosis has been made, signs that may help the surgeon
      determine if open or arthroscopic surgery would be best used are reviewed.
      Finally, the author reviews indications for a gluteus medius repair with
      concomitant gluteus maximus reconstruction.

PMID- 29354469
TI  - Arthroscopic Primary Anterior Cruciate Ligament Repair With Suture Augmentation.
AB  - Historically, poor results of open primary repair of anterior cruciate ligament
      (ACL) injuries have been reported. In hindsight, however, appropriate patient
      selection (i.e. proximal tears and good tissue quality) was not performed,
      because it has recently been recognized that good outcomes of primary ACL repair
      are possible when selectively performed in patients with proximal tears and good
      tissue quality. Moreover, with modern-day advances, arthroscopic primary repair
      can be an excellent treatment option for patients with proximal tears. Preserving
      the native ACL has several advantages, including maintaining native
      proprioceptive function and biology. The procedure is also minimally invasive and
      prevents the need for formal ACL reconstruction. Recently, it has been suggested
      that additional suture augmentation of the primary repair technique may be
      beneficial for protecting ligament healing during early range of motion. In this
      Technical Note, we present the surgical technique of arthroscopic primary repair
      with suture augmentation for patients with proximal ACL tears.

PMID- 29354470
TI  - Posterior Capsulotomy of the Knee: Treatment of Minimal Knee Extension Deficit.
AB  - The loss of knee extension, even if minimal, is disabling and considerably
      affects the individual's quality of life. This loss of extension can be a
      consequence of prior surgery, including a previous anterior cruciate ligament
      reconstruction. Although this loss of extension may be treated through an
      isolated arthroscopic procedure, a more severe case may warrant an invasive
      approach. In these cases, a posterior capsulotomy of the knee may be done if all
      conservative measures have been exhausted. This procedure has been proven to be
      safe and effective in the re-establishment of full extension in the setting of a
      minor flexion contracture of the knee. The purpose of this Technical Note was to
      describe our preferred technique when performing an open posterior capsulotomy of
      the knee for the treatment of minimal extension deficit.

PMID- 29354471
TI  - Quadriceps Tendon Repair Using Knotless Anchors and Suture Tape.
AB  - Repair of a torn quadriceps tendon is necessary to restore the extensor mechanism
      of the knee. Traditional repair involves transosseous sutures tied over bone
      bridges on the inferior pole of the patella. Suture anchor repair has been shown
      to be stronger than transosseous repair and facilitates a smaller incision.
      Suture tape can improve the strength of the suture-tendon interface, and when
      combined with knotless anchors, leads to a stronger repair construct than even
      traditional suture anchors and surgeon-tied knots. Here we describe our technique
      of quadriceps tendon repair using suture tape and knotless anchors.

PMID- 29354472
TI  - Systematic Arthroscopic Treatment of Diffuse Pigmented Villonodular Synovitis in
      the Knee.
AB  - Pigmented villonodular synovitis (PVNS) is a benign aggressive disease that
      presents in either a localized (LPVNS) or diffuse (DPVNS) form. Arthroscopic
      synovectomy is the standard operative treatment for LPVNS, and when used to treat
      DPVNS, it is usually combined with an open posterior procedure. The purpose of
      this Technical Note is to report the technique that we have refined to allow for
      arthroscopic synovectomy as the sole treatment for DPVNS. We describe our
      technique with the factors we have found to be important to ensure adequate
      arthroscopic synovectomy, while minimizing risks and complications. The
      combination of additional portals, the use of multiple different shavers and
      arthroscopes, and the use of a leg holder all maximize our ability to clear
      disease.

PMID- 29354473
TI  - Aquarium Portal Technique for PASTA Lesion Repair.
AB  - The simultaneous arthroscopic exposure of the subacromial and intra-articular
      space of the shoulder is challenging in the presence of only partial-thickness
      rotator cuff tears. We present our experience and method of entering the joint
      through the opened rotator cuff interval from an anterosuperior portal between
      the coracoid process and anterior acromion. With moderate (approximately 30
      degrees ) abduction and external rotation, the rotator interval opens readily,
      offering a view with the camera toward the anterior edge of the supraspinatus
      tendon. An anterior view on the anterior leading edge of the supraspinatus tendon
      is obtained, showing the subacromial space above and the glenohumeral space below
      the tendon, similar to the view in an aquarium. The rotator cuff can be elevated
      using a rod inserted intra-articularly from posterior, whereas anchors and other
      instruments may be inserted from lateral. This approach offers the advantages of
      full exposure of the posterior undersurface of the rotator cuff insertion; a
      convenient approximately 90 degrees  angle between the camera and instruments;
      and no need to change portals for anchor placement, tendon stitching, or suture
      handling. The objective of this Technical Note is to describe our arthroscopic
      repair approach (aquarium technique) to PASTA (partial articular supraspinatus
      tendon avulsion) lesions.

PMID- 29354474
TI  - Long Head of the Biceps as a Suitable Available Local Tissue Autograft for
      Superior Capsular Reconstruction: "The Chinese Way".
AB  - Massive irreparable rotator cuff tears remain a challenging condition during
      daily clinical practice. Irreversible fatty infiltration of muscles and excessive
      chronic retraction of tendons predispose to high failure rates of their surgical
      treatment. Superior capsular reconstruction with either fascia lata autograft or
      a dermal allograft patch is a newly described solution that could prevent
      superior humeral head migration and restore the anteroposterior shoulder muscle
      force couples. The purpose of this article is to propose a technical modification
      of superior capsular reconstruction using long head of the biceps tendon
      autograft. The tendon's insertion into the glenoid is left intact, whereas
      laterally, it is tenotomized, transferred, and sutured with anchors onto the
      footprint of the supraspinatus tendon acting as a superior static stabilizer of
      the shoulder joint. Although this surgical modification has theoretical
      biological advantages, could be performed with the least technical demands, and
      simplifies the original demanding procedure, further prospective studies with
      large cohort populations and long-term follow-up are necessary to establish its
      effectiveness.

PMID- 29354475
TI  - Circumferential Suture Repair of Isolated Horizontal Meniscal Tears Augmented
      With Fibrin Clot.
AB  - Traditionally, horizontal cleavage meniscus tears have been associated with
      osteoarthritis, indicative of the degenerative process. Recent treatment measures
      have focused on maintaining as much meniscal tissue as possible, despite the
      routine extension of these tears into the central white-white zones. In the
      absence of tunnel drilling for cruciate ligament reconstructions, the use of an
      exogenous fibrin clot is a useful adjunct to increase the local growth factors at
      the tear repair to aid in healing. This surgical technique is to describe the use
      of an all-arthroscopic tied circumferential suture repair of horizontal meniscal
      tears augmented with exogenous fibrin clot to treat all locations of horizontal
      meniscal tears.

PMID- 29354476
TI  - Meniscal Allograft Transplantation With Concomitant Osteochondral Allograft
      Transplantation.
AB  - Surgical strategies for knee joint preservation are numerous, with the
      procedure(s) of choice for a given patient dependent on the status of the
      articular cartilage, meniscus, overall alignment, and ligamentous stability. For
      patients with large, isolated, osteochondral defects of the articular cartilage
      of the femoral condyle, osteochondral allograft transplantation (OCA) is often
      performed in an effort to reduce pain and improve function. Similarly, for
      appropriately indicated patients with symptomatic meniscus deficiency, meniscus
      allograft transplantation (MAT) is an excellent surgical solution. Often patients
      require concomitant MAT and OCA as part of a joint preservation strategy. In this
      Technical Note, we describe the surgical technique for performing arthroscopic
      assisted concomitant lateral MAT and lateral femoral condyle OCA as part of a
      knee joint preservation strategy.

PMID- 29354477
TI  - Arthroscopic Treatment of Type 1B Triangular Fibrocartilage Complex Tear by
      "Outside-In" Repair Technique Using Transcapsular Transverse Mattress Suture.
AB  - Triangular fibrocartilage complex (TFCC) injuries are increasingly recognized as
      a cause of ulnar-sided wrist pain. Palmer grouped these tears into either
      traumatic or degenerative, with various subclassifications. Magnetic resonance
      imaging (MRI), arthrogram, and arthroscopy are the methods used to establish the
      diagnosis. Several arthroscopic methods of TFCC repair including outside-in,
      inside-out, and all-inside techniques have been described. The outside-in repair,
      which involves piercing the TFCC via the ulnar side of the wrist, has been
      described by several authors, but the technique varies among authors with respect
      to instrumentation and subtle surgical modifications. The purpose of this article
      was to present the technique of arthroscopic outside-in repair using transverse
      mattress suture for type 1B TFCC tear by modifying classic vertical mattress
      sutures into sutures that pass completely through the disc.

PMID- 29354478
TI  - Arthroscopic Triple Labral Repair in an Adolescent.
AB  - Traumatic glenohumeral dislocations often result in significant injury to the
      anterior-inferior labrum, most commonly leading to recurrent anterior
      instability. While in skeletally immature patients, shoulder trauma more commonly
      results in fracture versus a true dislocation, shoulder instability does occur
      and can be difficult to manage in the setting of open physes. In any event, the
      goal of treatment is to reduce the risk of recurrence and allow full
      participation in activities, including sports. Arthroscopic stabilization has
      been shown to be an effective treatment option for young patients, with good
      return to sport rates; however, the vast majority of literature on shoulder
      instability in the youth patient population focuses on anterior instability.
      Concomitant lesions of the anterior, posterior, and superior labrum have been
      rarely described in youth athletes and present a formidable clinical challenge,
      particularly in skeletally immature patients. In this Technical Note, we describe
      the authors' preferred technique for arthroscopic repair of a traumatic triple
      labral tear, including anterior, posterior, and type IV SLAP components, in
      adolescent patients.

PMID- 29354479
TI  - Arthroscopic Subscapularis Repair Through a Single Anterior Portal.
AB  - Arthroscopic subscapularis repair with knotted suture fixation typically requires
      use of both anterior and accessory superolateral portals with passage of suture
      through multiple anatomic spaces. The advent of knotless anchors has allowed for
      simplification of subscapularis repairs. In this report we describe a simple
      method of knotless arthroscopic subscapularis repair through a single anterior
      portal. The indication for a single-anterior portal knotless subscapularis repair
      is a complete tear of the upper one-third of the subscapularis. This approach can
      be used for isolated subscapularis repair or, in patients with multiple-tendon
      involvement, initial subscapularis repair to facilitate subsequent
      posterosuperior cuff repair.

PMID- 29354480
TI  - An All-Arthroscopic, Length-Tensioned Suprapectoral Biceps Tenodesis Technique.
AB  - Biceps tenodesis remains a popular choice for treating anterior shoulder pain in
      the setting of primary biceps tendinitis or biceps pain due to concomitant
      glenohumeral joint pathology. A variety of surgical approaches and fixation
      construct options are available for biceps tenodesis. The advantages of an all
      arthroscopic biceps tenodesis include anatomic maintenance of the length-tension
      relation with strength preservation and improved cosmetic results. This technique
      can be technically challenging but allows for a minimally invasive approach to
      anchor the biceps. In this Technical Note, we describe a suprapectoral biceps
      tenodesis using an all-arthroscopic approach in the setting of concomitant
      rotator cuff repair. This technique offers a viable alternative to the open
      subpectoral biceps tenodesis.

PMID- 29354482
TI  - Effect of educational intervention on attitudes toward the concept of criminal
      responsibility.
AB  - AIM: To evaluate the effect of educational intervention on individuals' knowledge
      of and attitudes toward forensic mental health. METHODS: We conducted a
      questionnaire regarding attitudes toward various ideas about forensic mental
      health. The respondents attended a 1-h seminar regarding forensic mental health
      after answering the questionnaire. On completion of the seminar, the respondents
      answered another questionnaire containing many of the same questions as contained
      in the pre-seminar questionnaire. RESULTS: A total of 86 individuals attended the
      seminar, and 78 responded to the questionnaire. Only 13 (18.8%) participants were
      supportive of the concept of criminal responsibility initially, and there was a
      statistically significant increase in those who became more supportive after the
      seminar, with 22 (33%) being supportive after the seminar (Wilcoxon signed-rank
      test, P < 0.001). Logistic regression analysis revealed that participants who
      were skeptical about forensic mental systems and those with fewer opportunities
      to see media reports regarding psychiatry were likely to become supportive of
      criminal responsibility after the intervention. CONCLUSION: These results suggest
      that public attitudes toward criminal responsibility and mental health can be
      influenced via educational interventions.

PMID- 29354483
TI  - Predictive power of statistical significance.
AB  - A statistically significant research finding should not be defined as a P-value
      of 0.05 or less, because this definition does not take into account study power.
      Statistical significance was originally defined by Fisher RA as a P-value of 0.05
      or less. According to Fisher, any finding that is likely to occur by random
      variation no more than 1 in 20 times is considered significant. Neyman J and
      Pearson ES subsequently argued that Fisher's definition was incomplete. They
      proposed that statistical significance could only be determined by analyzing the
      chance of incorrectly considering a study finding was significant (a Type I
      error) or incorrectly considering a study finding was insignificant (a Type II
      error). Their definition of statistical significance is also incomplete because
      the error rates are considered separately, not together. A better definition of
      statistical significance is the positive predictive value of a P-value, which is
      equal to the power divided by the sum of power and the P-value. This definition
      is more complete and relevant than Fisher's or Neyman-Peason's definitions,
      because it takes into account both concepts of statistical significance. Using
      this definition, a statistically significant finding requires a P-value of 0.05
      or less when the power is at least 95%, and a P-value of 0.032 or less when the
      power is 60%. To achieve statistical significance, P-values must be adjusted
      downward as the study power decreases.

PMID- 29354481
TI  - Disorders of metal metabolism.
AB  - Trace elements are chemical elements needed in minute amounts for normal
      physiology. Some of the physiologically relevant trace elements include iodine,
      copper, iron, manganese, zinc, selenium, cobalt and molybdenum. Of these, some
      are metals, and in particular, transition metals. The different electron shells
      of an atom carry different energy levels, with those closest to the nucleus being
      lowest in energy. The number of electrons in the outermost shell determines the
      reactivity of such an atom. The electron shells are divided in sub-shells, and in
      particular the third shell has s, p and d sub-shells. Transition metals are
      strictly defined as elements whose atom has an incomplete d sub-shell. This
      incomplete d sub-shell makes them prone to chemical reactions, particularly redox
      reactions. Transition metals of biologic importance include copper, iron,
      manganese, cobalt and molybdenum. Zinc is not a transition metal, since it has a
      complete d sub-shell. Selenium, on the other hand, is strictly speaking a
      nonmetal, although given its chemical properties between those of metals and
      nonmetals, it is sometimes considered a metalloid. In this review, we summarize
      the current knowledge on the inborn errors of metal and metalloid metabolism.

PMID- 29354484
TI  - Shortness of breath in clinical practice: A case for left atrial function and
      exercise stress testing for a comprehensive diastolic heart failure workup.
AB  - The symptom cluster of shortness of breath (SOB) contributes significantly to the
      outpatient workload of cardiology services. The workup of these patients includes
      blood chemistry and biomarkers, imaging and functional testing of the heart and
      lungs. A diagnosis of diastolic heart failure is inferred through the exclusion
      of systolic abnormalities, a normal pulmonary function test and normal
      hemoglobin, coupled with diastolic abnormalities on echocardiography.
      Differentiating confounders such as obesity or deconditioning in a patient with
      diastolic abnormalities is difficult. While the most recent guidelines provide
      more avenues for diagnosis, such as incorporating the left atrial size, little
      emphasis is given to understanding left atrial function, which contributes to at
      least 25% of diastolic left ventricular filling; additionally, exercise stress
      testing to elicit symptoms and test the dynamics of diastolic parameters,
      especially when access to the "gold standard" invasive tests is lacking, presents
      clinical translational gaps. It is thus important in diastolic heart failure work
      up to understand left atrial mechanics and the role of exercise testing to build
      a comprehensive argument for the diagnosis of diastolic heart failure in a
      patient presenting with SOB.

PMID- 29354485
TI  - Is forced oscillation technique the next respiratory function test of choice in
      childhood asthma.
AB  - Respiratory diseases, especially asthma, are common in children. While spirometry
      contributes to asthma diagnosis and management in older children, it has a
      limited role in younger children whom are often unable to perform forced
      expiratory manoeuvre. The development of novel diagnostic methods which require
      minimal effort, such as forced oscillation technique (FOT) is, therefore, a
      welcome and promising addition. FOT involves applying external, small amplitude
      oscillations to the respiratory system during tidal breathing. Therefore, it
      requires minimal effort and cooperation. The FOT has the potential to facilitate
      asthma diagnosis and management in pre-school children by faciliting the
      objective measurement of baseline lung function and airway reactivity in children
      unable to successfully perform spirometry. Traditionally the use of FOT was
      limited to specialised centres. However, the availability of commercial equipment
      resulted in its use both in research and in clinical practice. In this article,
      we review the available literature on the use of FOT in childhood asthma. The
      technical aspects of FOT are described followed by a discussion of its practical
      aspects in the clinical field including the measurement of baseline lung function
      and associated reference ranges, bronchodilator responsiveness and bronchial
      hyper-responsiveness. We also highlight the difficulties and limitations that
      might be encountered and future research directions.

PMID- 29354486
TI  - Quantitative comparison of cranial approaches in the anatomy laboratory: A
      neuronavigation based research method.
AB  - AIM: To describe the development and validation of a novel neuronavigation-based
      method, which allows the quantification of the anatomical features that define an
      approach, as well as real-time visualization of the surgical pyramid. METHODS:
      The method was initially developed with commercially-available hardware for
      coordinate collection (a digitizer and a frameless navigation system) and
      software for volume rendering; dedicated neuronavigation software
      (ApproachViewer, part of GTx-UHN) was then developed. The accuracy of
      measurements and the possibility of volumetric rendering of surgical approaches
      simulated in a phantom were compared among three different methods and
      commercially-available radiological software. In the anatomy laboratory,
      ApproachViewer was applied to the comparative quantitative analysis of multiple
      neurosurgical approaches and was used by many surgeons who were untrained for the
      research method. RESULTS: The accuracy of ApproachViewer is comparable to
      commercially-available radiological software. In the anatomy laboratory, the
      method appears versatile. The system can be easily used after brief training.
      ApproachViewer allows for real-time evaluation and comparison of surgical
      approaches, as well as post-dissection analyses of collected data. The accuracy
      of the method depends on the navigation registration: with a 1-2 mm registration
      error, it is adequate for evaluation and comparison of most neurosurgical
      approaches. CONCLUSION: This new research method and software allows semi
      automated visualization, quantification, and comparison of neurosurgical
      approaches in the anatomy laboratory.

PMID- 29354487
TI  - Laparoscopic-extracorporeal surgery performed with a fixation device for adnexal
      masses complicating pregnancy: Report of two cases.
AB  - The potential complications associated with an adnexal mass discovered during
      early pregnancy call for surgical treatment. Ideally, surgery is performed after
      gestational week 12, but uterine expansion after the first trimester makes
      surgery difficult. We report two pregnancies complicated by adnexal masses for
      which we used an organ fixation device for safe performance of single-site
      umbilical laparoscopic surgery. Pelvic magnetic resonance imaging depicted a
      dichorionic, diamniotic twin pregnancy and 60-mm right adnexal mass in the first
      patient and bilateral adnexae in the second. All three masses were suspected
      mature cystic teratomas. Both patients underwent laparoscopic surgery during
      gestational week 14. With use of an organ fixation device, traction was applied
      until the mass reached the umbilicus; tumor resection was performed
      extracorporeally. In the second patient, the second mass was simply aspirated
      because adhesions were encountered. Our single-site laparoscopic-extracorporeal
      technique proved to be a safe approach to an otherwise high-risk situation.

PMID- 29354488
TI  - Impact of the Ki-67 labeling index and p53 expression status on disease-free
      survival in pT1 urothelial carcinoma of the bladder.
AB  - Background: The identification of protein biomarkers to guide treatment decisions
      regarding adjuvant therapies for high-risk non-muscle-invasive bladder cancer
      (NMIBC) has been of increasing interest. Evidence of the impact of tumor
      suppressor gene product p53 and cell proliferation marker Ki-67 on oncologic
      outcomes in bladder cancer patients at highest risk of recurrence and progression
      is partially contradictory. We sought to mirror contemporary expression patterns
      of p53 and Ki-67 in a select cohort of patients with pT1 bladder cancer. Methods:
      Patients from four Northern German institutions with a primary diagnosis of pT1
      bladder cancer between 2009 and 2016 and complete data regarding p53 or Ki-67
      expression status were included for final analyses. Baseline patient
      characteristics (age, gender, age-adjusted Charlson comorbidity index) and tumor
      characteristics [diagnostic sequence, tumor focality, concomitant carcinoma in
      situ, 1973 World Health Organization (WHO) grading, lymphovascular invasion,
      adjuvant instillation therapy] were abstracted by retrospective chart review.
      Immunohistochemistry for detection of p53 and Ki-67 expression was performed
      according to standardized protocols. Microscopic analyses were performed by
      central pathologic review. First, we compared patients with positive vs. negative
      p53 expression and Ki-67 labeling index [>40% vs. <=40%; cutoffs based on best
      discriminative ability in univariable Cox regression analysis with disease-free
      survival (DFS) as endpoint] with regard to baseline and tumor characteristics.
      Second, we evaluated the effect of biomarker positivity on DFS by plotting
      univariable Kaplan-Meier curves and performing uni- and multivariable Cox
      regression analyses. Results: Of 102 patients with complete information on p53
      status, 44 (43.1%) were p53 positive, and they more often harbored concomitant
      carcinoma in situ (50.0% vs. 27.6%; P=0.032) and 1973 WHO grade 3 (97.7% vs.
      69.0%; P=0.001) compared to their p53 negative counterparts. Of 79 patients with
      complete information on Ki-67 expression status, 30 (38.0%) had a labeling index
      >40%. Mean Ki-67 labeling index was higher in WHO grade 3 vs. grade 2 tumors
      (45.8 vs. 29.7; P=0.004). At a median follow-up of 51.0 months, 31/91 patients
      with complete follow-up information (34.1%) suffered from disease recurrence or
      progression. In univariable Kaplan-Meier analyses, no difference regarding DFS
      was found in p53 positive vs. negative (P=0.8) or Ki-67 labeling index >40% vs.
      <=40% (P=0.078) patients. In multivariable analyses, Ki-67 labeling index >40%
      remained an independent predictor of DFS [hazard ratio (HR), 2.66; 95% confidence
      interval (CI), 1.02-6.95; P=0.046], after adjusting for p53 expression and
      lymphovascular invasion. However, p53 status was not associated with our endpoint
      (P=0.8). Conclusions: While we found an association of a Ki-67 labeling index
      >40% and shorter DFS in pT1 bladder cancer patients, this did not hold true for
      p53 positivity. Future research is needed to identify additional microscopic and
      molecular risk factors and biomarker panels to improve risk stratification and
      guide adjuvant therapies in those patients.

PMID- 29354489
TI  - The landscape of genetics and biomarkers in bladder cancer.

PMID- 29354491
TI  - Opportunities of next-generation sequencing in non-muscle invasive bladder cancer
      outcome prediction.
AB  - Bladder cancer (BC) is a common disease in both sexes and majority of cases
      present as non-muscle invasive BC (NMIBC). The percentage of NMIBC progressing to
      muscle invasive BC (MIBC) varies between 25% and 75% and currently there are no
      reliable biomarkers that may predict the outcome of high-risk (HR) NMIBC. Whilst
      The Cancer Genome Atlas (TCGA) project has identified genetic alteration in MIBC
      using next-generation sequencing (NGS), genetic data in HR-NMIBC outcome
      prediction using this new technology are limited. We reviewed data on NGS
      performed on DNA and RNA extracted from tissue, plasma and urinary samples
      obtained from patients with NMIBC. Analysis on different specimens revealed
      genetic alterations and microRNA alterations in common oncogenic pathways such as
      gene expression (TERT) and cell proliferation (PTEN, cyclin D). Validation of a
      12-gene (CDC25B, KPNA2, BIRC5, COL18A1, MSN, UBE2C, COL4A1, FABP4, MBNL2, SKAP2,
      COL4A3BP, NEK1) progression score has shown significant association with
      progression. ARID1A mutations are associated with an increased risk of recurrence
      after Bacillus Calmette-Guerin (BCG) together with a high DNA damage repair (DDR)
      gene alterations in HR-NMIBC. Patients with progressive disease seem to have
      significantly higher levels of both plasma and urinary tumour DNA compared with
      patients with recurrence. Although experimental data appear promising, well
      designed systematic studies are urgently needed to translate applicability to
      clinical practice.

PMID- 29354490
TI  - The contemporary role and impact of urine-based biomarkers in bladder cancer.
AB  - Despite advances in the surgical and medical treatment of bladder cancer, there
      have only been minor improvements in mortality and morbidity rates over the past
      decades. Urine-based markers help to improve diagnosing bladder cancer with the
      aim of complementing or probably in future replacing cystoscopy. Biomarkers may
      allow individualized risk stratification and support decision-making regarding
      therapy and follow-up. This review summarizes the existing urine-based biomarkers
      in bladder cancer. We conducted a comprehensive review of the literature. We
      conducted a PubMed/Medline based research on English language articles and
      selected original articles and review articles that provided both description and
      assessment of urinary markers at time of screening, initial diagnosis, monitoring
      and prognostic evaluation of urothelial bladder cancer. Our research covered
      studies published between 2000 and 2017. The aim of this study was to give
      clinicians keys to understand the existing or promising urinary markers that may
      become alternatives to cytology/cystoscopy pair in the near future. Many urinary
      markers are now available, often with superior sensitivity to cytology. Their
      uses have been evaluated in numerous clinical situations in addition to the time
      of initial diagnosis and surveillance such as cases of isolated macroscopic
      hematuria or atypical cytology discordant with the rest of the explorations.
      However, their superiority over the cytology/cystoscopy association is not
      demonstrated. These new markers are lacking for the most part of standardization
      and simplicity making their use in common practice difficult. the types and forms
      of these new markers are very heterogeneous among themselves and between the
      studies that evaluate them. Well-designed protocols and prospective, controlled
      trials are needed to provide the basis to determine whether integration of urine-
      and blood-based biomarkers into clinical decision-making will be of value for
      bladder cancer detection and screening in the future.

PMID- 29354492
TI  - Peri-operative chemotherapy for muscle-invasive bladder cancer: status-quo in
      2017.
AB  - The role of perioperative chemotherapy associated with radical cystectomy (RC)
      for muscle-invasive bladder cancer has been analyzed in several landmark
      randomized controlled trials (RCTs) over the past decades. With regard to
      neoadjuvant chemotherapy (NAC), a meta-analysis of level 1 evidence and long-term
      results from the largest RCTs support its use, which is currently advocated as
      the standard of care by most of the clinical guidelines worldwide. However, with
      regard to the delivery of adjuvant chemotherapy (AC), evidence is more
      contentious. Specifically, several meta-analyses demonstrated a survival benefit
      associated with the use of cisplatin-based regimen but investigators identified
      multiple methodological limitations in most of included RCTs. Nonetheless, AC is
      currently considered for fit patients with adverse pathological features at RC.
      It is noteworthy that the delivery of such cytotoxic treatment after surgery may
      maintain significant anti-tumor activity even in those patients who previously
      received NAC. Finally, given its greater response rate, the methotrexate,
      vinblastine, adriamycin plus cisplatin combination remains preferentially
      considered in the neoadjuvant setting, while the gemcitabine plus cisplatin
      combination is more commonly delivered in the adjuvant setting because of its
      better toxicity profile. However, no prospective evidence comparing efficacy of
      both regimens for NAC or AC is currently available.

PMID- 29354493
TI  - Different stages in drug development for muscle-invasive bladder cancer.
AB  - Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease. Despite
      optimal therapy, half of the patients will succumb to disease. This prognosis
      could not be improved over the last three decades. Therefore, MIBC is left behind
      from other cancers such as prostate, where novel treatment options were
      discovered and improve patient outcomes. While being aware of the recent emerging
      evidence of checkpoint inhibition in MIBC, we aim to describe different stages of
      drug development in MIBC by using three specific targets. On the example of Her2
      targeting, we aimed to indicate, that either a target is ineffective in MIBC or
      that the patient selection is insufficient. The first clinical trials using a pan
      fibroblast growth factor receptor (panFGFR) inhibitor to target the FGFR pathway
      showed promising results. Data of further trials are to be awaited before
      implementing these drugs into daily clinical practice. A large variety of novel
      agents are investigated in vitro and in vivo. On the example of a malaria
      protein, we aimed to discuss a treatment paradigm that is not dependent on
      pathway signaling and the genomic landscape of MIBC. The ultimate question still
      remains to be answered: How do we select the optimal treatment for the right
      patient?

PMID- 29354494
TI  - Do we have biomarkers to predict response to neoadjuvant and adjuvant
      chemotherapy and immunotherapy in bladder cancer?
AB  - Radical cystectomy (RC) is the standard of care treatment of localized muscle
      invasive bladder cancer (BC). However, about 50% of patients develop metastases
      within 2 years after cystectomy. Neoadjuvant cisplatin-based chemotherapy before
      cystectomy improves the overall survival (OS) in patients with muscle-invasive
      BC. Pathological response to neoadjuvant treatment is a strong predictor of
      better disease-specific survival. Nevertheless, some patients do not benefit from
      chemotherapy. The identification of reliable biomarkers enabling clinicians to
      identify patients who might benefit from chemotherapy is a very important
      clinical task. An identification tool could lead to individualized therapy,
      optimizing response rates. In addition, unnecessary treatment with chemotherapy
      which potentially leads to a loss of quality of life and which might also might
      cause a delay of cystectomy in a neoadjuvant setting could be avoided. The
      present review aims to summarize and discuss the current literature on biomarkers
      for the prediction of response to systemic therapy in muscle-invasive BC.
      Tremendous efforts in genetic and molecular characterization have led to the
      identification of predictive candidate biomarkers in urothelial carcinoma (UC),
      although prospective validation is pending. Ongoing clinical trials examining the
      benefit of individual therapies in UC of the bladder (UCB) by molecular patient
      selection hold promise to shed light on this question.

PMID- 29354495
TI  - Genetic determinants for chemo- and radiotherapy resistance in bladder cancer.
AB  - Bladder cancer (BCa) is burdened by high rates of chemo- and radio-resistance. We
      reviewed and summarized the current evidence regarding the genetic determinants
      of resistance in patients treated with chemotherapy and/or radiotherapy (RT) for
      BCa. Genetic heterogeneity may preexist to treatment arising with tumorigenesis
      or increasing progressively during the treatment. Several biological pathways
      seem to be involved in the cellular response to treatment. These pathways
      comprehend mechanisms leading to modify the intracellular concentration of the
      drug, mechanisms leading to increase the repair of DNA damage caused by the
      treatment, mechanisms leading to increase cell survival, despite DNA damage,
      acting on the signaling pathways affecting apoptosis, mechanisms promoting
      autophagy. In the present review, we focused on the genetic determinants of
      resistance affecting the aforementioned mechanisms.

PMID- 29354497
TI  - Current markers and their value in the era of immuno-oncology.
AB  - Immunotherapy in urothelial cancer is a quickly evolving field as new agents are
      being investigated in multiple clinical trials and various clinical settings. The
      purpose of this review is to provide an insight into the mechanism of these
      treatments, potential targets to evaluate treatment response and to give an
      update on the current status of clinical trials. Urothelial cancer is a
      polyclonal disease with a substantial tumor heterogeneity and a high mutational
      load which may be beneficial as this may trigger a stronger T-cell mediated
      immune response. PD-1 expression has been shown to correlate with stage, grade,
      progression and poorer survival but it appears challenging to be utilized as a
      predictor for treatment response in urothelial cancer. Another important concept
      is immune cell (IC) infiltration, which is a reflection of the activated immune
      response within the target tissue. Marker genes may represent signaling pathways
      involved in T-cell recognition and lysis of T-cells. The complexity of the tumor
      and host interaction requires multiple concepts to be integrated into a future
      model to assess treatment response. We have evaluated multiple biomarker
      approaches currently investigated in clinical trials in urothelial cancer.

PMID- 29354498
TI  - Perspective on cytoreduction and metastasis-directed therapy in node positive and
      metastatic urothelial carcinoma of the bladder.
AB  - The outcome of node positive or metastatic urothelial carcinoma of the bladder
      (mUCB) is poor and palliative chemotherapy has long been considered the only
      treatment option for this patient group. Cytoreduction and metastasis-directed
      therapy, either by surgery or radiotherapy, has been successfully applied in
      other metastatic solid tumors in order to increase survival. In this article, we
      explore the literature supporting cytoreduction and metastasis-directed therapy
      in node positive and mUCB and try to define a patient cohort that could benefit
      from these treatments. From these data, it is clear that a selected group of
      patients survive a long time or could even be cured, however the data are scarce
      and the level of evidence is low. The criteria of a randomized clinical trial, to
      deliver the necessary evidence, are proposed.

PMID- 29354496
TI  - The current status and clinical value of circulating tumor cells and circulating
      cell-free tumor DNA in bladder cancer.
AB  - Urothelial carcinoma of the bladder (UCB) is a complex disease, which is
      associated with highly aggressive tumor biologic behavior, especially in patients
      with muscle-invasive and advanced tumors. Despite multimodal therapy options
      including surgery, radiotherapy and chemotherapy, UCB patients frequently suffer
      from poor clinical outcome. Indeed, the potential of diverse opportunities for
      modern targeted therapies is not sufficiently elucidated in UCB yet. To improve
      the suboptimal treatment situation in UCB, biomarkers are urgently needed that
      help detecting minimal residual disease (MRD), predicting therapy response and
      subsequently prognosis as well as enabling patient stratification for further
      therapies and therapy monitoring, respectively. To date, decision making
      regarding treatment planning is mainly based on histopathologic evaluation of
      biopsies predominantly derived from the primary tumors and on clinical staging.
      However, both methods are imperfect for sufficient outcome prediction. During
      disease progression, individual disseminated tumor cells and consecutively
      metastases can acquire characteristics that do not match those of the
      corresponding primary tumors, and often are only hardly assessable for further
      evaluation. Therefore, during recent years, strong efforts were directed to
      establish non-invasive biomarkers from liquid biopsies. Urine cytology and serum
      tumor markers have been established for diagnostic purposes, but are still
      insufficient as universal biomarkers for decision-making and treatment of UCB
      patients. To date, the clinical relevance of various newly established blood
      based biomarkers comprising circulating tumor cells (CTCs), circulating cell-free
      nucleic acids or tumor-educated platelets is being tested in cancer patients. In
      this review we summarize the current state and clinical application of CTCs and
      circulating cell-free tumor DNA originating from blood as biomarkers in patients
      with different UCB stages.

PMID- 29354500
TI  - Describing the learning curve for bulbar urethroplasty.
AB  - Background: Learning curves have been described for a number of urological
      procedures including radical prostatectomy and laparoscopic nephrectomy but
      rarely for urethroplasty. We describe the learning curve for bulbar urethroplasty
      in a single surgeon series. Methods: A retrospective case note review was
      performed of 91 consecutive men median age 32 years (range, 15-66 years) having
      bulbar urethroplasty performed by a single surgeon. Data was collected on type of
      urethroplasty, restricture rate (as defined by urethrogram and/or flow rate) and
      duration of follow up. The restricture rates were compared by quartiles and
      statistical analysis was by |O2 between the first and fourth quartiles. Results:
      The 91 men had 42 dorsal onlay buccal mucosal graft (Dorsal BMG), 20 BMG
      augmented bulbobulbar anastomotic (Augmented Rooftop) and 29 bulbobulbar
      anastomotic (BBA) urethroplasties performed. Median follow up was 39 months for
      the first quartile, 42 months for the second, 36 months for the third, and 35
      months for the fourth. The restricture rate was 17% in the first quartile, 8.7%
      in the second and third quartiles and 4.5% in the fourth quartile. There were no
      restrictures noted after 24 months. There were 4 restrictures in the first
      quartile and 1 restricture in the fourth quartile (|O2 P<0.01). Conclusions:
      There is a statistically and clinically significant difference in restricture
      rates between first and fourth quartiles with rates falling from 17% to 4.5%.
      There is a learning curve for bulbar urethroplasty with a reduced restricture
      rate each quartile and it may take as many as 90 cases to reach optimum
      restricture rates.

PMID- 29354499
TI  - Online tools for patient counseling in bladder and kidney cancer-ready for prime
      time?
AB  - Gauging prognosis is a key element when facing treatment decisions in cancer
      care. Several prognostic tools, such as risk tables and nomograms are at hand to
      aid this process. In the context of patient-centered care, prognostic tools are
      of great interest to caregivers and -providers alike, as they can convey sizeable
      amounts of information and provide tailored, accurate estimates of prognosis.
      Given the rising number of prognostic tools in cancer care over the last two
      decades, and similarly, ever increasing presence of the Internet, we aimed to
      assess how this would translate into the availability of online tools for patient
      counseling. We used a modified systematic review to evaluate the web-based
      availability, format, and content of prognostic tools for bladder and kidney
      cancer care. Our search identified a total of twenty-three tools, offered by
      eight providers, which assessed a total of six (bladder cancer) and five (kidney
      cancer) different outcomes. Despite the restricted availability of online tools,
      we observed that the majority showed limited user-friendliness (including, for
      example, a statement/explanation of intended use, visualization of data,
      availability as application software for handheld devices). Only one tool
      included modifiable risk factors such as smoking behavior and body weight.
      Lastly, none of the tools incorporated genomic or molecular markers or treatment
      associated quality of life. Taken together, online tools for patient counseling
      in bladder and kidney cancer care are only beginning to align with the growing
      need in clinical reality. Further and future avenues include incorporation of
      health-related quality of life as well as genomic and biomarkers into prediction
      tools.

PMID- 29354501
TI  - Predicting success after artificial urinary sphincter: which preoperative factors
      drive patient satisfaction postoperatively?
AB  - Background: To determine which preoperative factors drive patient-reported
      quality of life (QoL) after artificial urinary sphincter (AUS) implantation.
      Methods: Men receiving AUS after prostate cancer treatment were identified from a
      prospectively collected dataset. Preoperative factors were recorded during the
      initial incontinence consultation. Patients underwent urodynamic testing (UDS)
      preoperatively at surgeon discretion. Patients were surveyed by telephone
      postoperatively and given the EPIC Urinary Domain (EPIC-UD) and Urinary Distress
      Inventory (UDI-6) questionnaires. Differences in postoperative maximum pads per
      day (MxPPD) and questionnaire scores were compared across preoperative factors,
      with P!U0.05 indicating statistical significance. Results: Telephone survey was
      completed by 101 of 238 patients (42%). Median age was 69 [63-75] years, BMI was
      29 [26-32] kg/m2. MxPPD was 5 [3-9] preoperatively and 2 [1-3] postoperatively
      (r=0.255, P=0.011). Postoperative median EPIC-UD was 82 [67-89] and UDI-6 was 22
      [11-36]. Postoperative MxPPD was lower in patients who reported being able to
      store urine before AUS {2 [1-2] vs. 2 [1-4], P=0.046}, and lower with
      urodynamically-proven detrusor overactivity (DO) {1.5 [1-2] with vs. 2 [1-4]
      without, P=0.050}. Detrusor pressure at maximum flow was negatively associated
      with QoL as measured by EPIC-UD score (r=-0.346, P=0.013) and UDI-6 score
      (r=0.413, P=0.003). Although 41 (41%) patients had a history of radiation,
      postoperative outcomes did not significantly differ with or without a history of
      radiation. Conclusions: Few preoperative factors predict QoL after AUS insertion.

PMID- 29354502
TI  - In vitro head-to-head comparison of the durability, versatility and efficacy of
      the NGage and novel Dakota stone retrieval baskets.
AB  - Background: To compare head to head two end-engaging nitinol stone retrieval
      devices available to urologists, in terms of durability, versatility and
      efficacy. Methods: For durability testing, 30 NGage and Dakota baskets were
      cycled 20 times between grasping and releasing synthetic stone models and
      evaluated for damage or device failure. For versatility and efficacy testing,
      baskets were assessed in their ability to capture and release stone models from 1
      to 11 mm. Each stone was raised above the capture site and the basket was opened
      to passively release the stone. If the stone did not release, the basket handle
      was shaken and the OpenSure feature employed if needed. Manual release was used
      as a last resort. Results: Durability-the Cook NGage demonstrated a statistically
      significant increased rate of visible device breakdown (P=0.0046) in 8 of 30
      (26.7%) devices vs. 0 of 30 Dakota devices, with mean damage at 13.5 cycles.
      Versatility and efficacy-both 8 mm baskets successfully captured stones from 1-8
      mm. The Dakota more effectively released 7-8 mm stones (P<0.0001). NGage required
      manual release of 8 mm stones in 13 cases compared to none with Dakota. For 11 mm
      baskets, the Dakota released all stones up to 10 mm with simple opening, while
      the NGage released 10 of 15 (67%) of 9 mm stones and 1 of 15 (7%) of 10 mm stones
      by simple opening. For 11 mm stones, the Dakota captured 100% whereas NGage could
      not capture any. Conclusions: Both baskets showed similar durability
      characteristics. The Dakota basket more effectively captured and released stones
      over 7 mm, as compared to the NGage basket. The OpenSure aspect conferred an
      advantage in handling and release of larger stones. These in vitro results
      demonstrate potential versatility, durability and efficacy of the Dakota basket.

PMID- 29354503
TI  - Frequency and severity of chronic scrotal pain in Canadian men presenting to
      urologists for infertility investigations.
AB  - Background: Chronic scrotal pain (CSP) may be debilitating in men presenting for
      treatment for CSP, but we have little information on the frequency and severity
      of CSP in the men who do not seek care for the CSP. Our objective was to identify
      the frequency and characteristics of CSP in a population of men presenting for
      reasons other than CSP to a urology clinic. Methods: Men presenting to a urology
      clinic for investigation of male infertility (INF) completed a standardized CSP
      questionnaires if they self-reported having CSP. This prospectively collected
      database was then retrospectively analyzed. Results: Forty-five of 1,203 (3.7%)
      of INF patients (mean age 35: range, 24-59), reported having CSP (INF/CSP). Our
      comparison group was 131 men presenting for investigation of CSP [mean age 43!A12
      (SD) years with a mean duration of CSP of 4.7!A5.95 years]. On average, men with
      INF/CSP had less severe and frequent pain than those with CSP, with significantly
      less pain during "bad" pain episodes (5.2!A2.2 vs. 7.4!A2.1, VAS score 0-10,
      P<0.0001 Student's t-test), less frequent "bad" pain episodes (23%!A21% vs.
      42%!A30% of the time, P<0.0001 Student's t-test) and lower proportion of men who
      reported having severe pain (VAS score 7-10/10) (4/45 vs. 46/131, P<0.001, chi
      squared test). Both groups reported a negative impact of the pain on quality of
      life (QOL), with 60% and 86% of men with INF/CSP and CSP alone reporting that
      they would feel 'mostly dissatisfied', 'unhappy', or 'terrible' if they had to
      continue life with their present scrotal pain symptoms. Conclusions: Clinicians
      should be aware that CSP is common among men presenting for conditions other than
      CSP and that even if the pain levels are not "severe", the chronic pain often has
      a significant negative impact on QOL.

PMID- 29354504
TI  - Multispecialty retrospective review of the clinical utility of pelvic magnetic
      resonance imaging in the setting of pelvic pain.
AB  - Background: Pelvic pain is a common complaint, and management of it is often
      difficult. We sought to evaluate the utility of magnetic resonance imaging (MRI)
      in the diagnosis of male pelvic pain. Though MRIs are commonly ordered to
      evaluate pelvic pain, there are very few studies obtaining the efficacy of pelvic
      MRI in determining a definitive diagnosis. The primary aim of our study was to
      evaluate the clinical utility of pelvic MRI for a diagnosis code that included
      pain. Methods: After receiving institutional review board approval, a
      retrospective study was performed of all pelvic MRIs completed at our institution
      from January 2, 2010 to December 31, 2014. These were further delineated into
      ordering providers by specialty and urology-specific International Classification
      of Diseases, Ninth Revision (ICD-9) code diagnoses (male pelvic pain,
      prostatitis, groin pain, scrotal pain, testicular pain, and penile pain).
      Clinical utility was defined as positive if MRI findings resulted in a change in
      management. Subanalysis was performed on patients with an ICD-9 co-diagnosis of
      previous oncologic concern. Results: A total of 2,643 pelvic MRIs were ordered at
      our institution over a 5-year period. Of these, 597 pelvic MRIs (23%) were
      ordered for a diagnosis code that included pain (hip pain, rectal pain, joint
      pain, penile pain, scrotal pain, male pelvic pain and orchitis). Total utility
      for MRIs to find anatomic abnormalities potentially responsible for the present
      pain was 34% (205/597). When ordered by urologic providers, utility was 23%.
      Oncologists represented the highest positivity rate at 57%. Conclusions: Chronic
      pelvic pain is a multispecialty complaint that is difficult to treat. We were
      surprised to find the large number of both specialists and generalists invested
      in the management of pelvic pain. The increasing availability of MRI technology
      makes it a likely candidate to test for a clinically significant anatomic reason
      for pain. Though MRI is a test with minimal adverse effect and no increased risk
      of radiation exposure, the cost on the healthcare system should be offset by a
      clear clinical utility. We found total utility to be 34% across all ordering
      providers and an increase in positivity with concern of oncologic disease.
      Therefore, we would recommend pelvic MRIs in the evaluation of patients with
      refractory pelvic pain.

PMID- 29354505
TI  - Degree of twisting and duration of symptoms are prognostic factors of testis
      salvage during episodes of testicular torsion.
AB  - Background: Testicular torsion is surgical emergency. Prompt diagnosis and
      treatment of testicular torsion is essential for testicular viability. At
      surgical exploration, the spermatic cord is seen twisted a variable number of
      times around its longitudinal axis. There is scant data regarding the degree of
      twisting and its association with testis outcomes. The purpose of our study is to
      explore how the degree of torsion factors into testicular outcome using follow-up
      data. Methods: We retrospectively reviewed the records of adolescent males who
      presented with testicular torsion to our institution, looking at duration of pain
      symptoms, degree of torsion documented in the operative note, procedure performed
      (orchiopexy versus orchiectomy), and follow-up clinic data for whether testicular
      atrophy after orchiopexy was present. A non-salvageable testis was defined as
      orchiectomy or atrophy. Receiver operator characteristics (ROC), multivariate,
      and logistic regression analyses were performed to determine the probability of a
      non-salvageable torsed testis based on time and degree of twisting. Results:
      Eighty-one patients met our study criteria, with 55 testes deemed viable and 26
      non-salvageable. We found a 25.7% atrophy rate after orchiopexy. Cut-off values
      of 8.5 h and 495 degrees of torsion would provide sensitivities of 73% and 53%,
      respectively, with specificity of 80% for both. Only duration and age were
      correlated with the risk of non-salvage on multivariate analysis. Logistic
      regression generated linear probability formulas of 4 + (3 !A hours) and 7 +
      (0.05 !A degrees) in calculating the probability of non-salvage with strong
      correlation. Conclusions: We were able to derive separate formulas to determine
      the viability of the torsed testis based on symptom duration and degrees of
      twisting. Fifteen h of symptoms and 860 degrees of torsion gives testes a 50%
      salvage rate. Interestingly, we also found that about 1 out of every 4 testes
      undergoes atrophy after orchiopexy.

PMID- 29354506
TI  - Inflatable penile prosthesis implant length with baseline characteristic
      correlations: preliminary analysis of the PROPPER study.
AB  - Background: "Prospective Registry of Outcomes with Penile Prosthesis for Erectile
      Restoration" (PROPPER) is a large, multi-institutional, prospective clinical
      study to collect, analyze, and report real-world outcomes for men implanted with
      penile prosthetic devices. We prospectively correlated co-morbid conditions and
      demographic data with implanted penile prosthesis size to enable clinicians to
      better predict implanted penis size following penile implantation. We present
      many new data points for the first time in the literature and postulate that
      radical prostatectomy (RP) is negatively correlated with penile corporal length.
      Methods: Patient demographics, medical history, baseline characteristics and
      surgical details were compiled prospectively. Pearson correlation coefficient was
      generated for the correlation between demographic, etiology of ED, duration of
      ED, co-morbid conditions, pre-operative penile length (flaccid and stretched) and
      length of implanted penile prosthesis. Multivariate analysis was performed to
      define predictors of implanted prosthesis length. Results: From June 2011 to June
      2017, 1,135 men underwent primary implantation of penile prosthesis at a total of
      11 study sites. Malleable (Spectra), 2-piece Ambicor, and 3-piece AMS 700 CX/LGX
      were included in the analysis. The most common patient comorbidities were CV
      disease (26.1%), DM (11.1%), and PD (12.4%). Primary etiology of ED: RP (27.4%),
      DM (20.3%), CVD (18.0%), PD (10.3%), and Priapism (1.4%), others (22.6%). Mean
      duration of ED is 6.2!A4.1 years. Implant length was weakly negatively correlated
      with White/Caucasian (r=-0.18; P<0.01), history of RP (r=-0.13; P<0.01), PD as
      comorbidity (r=-0.16; P<0.01), venous leak (r=-0.08; P<0.01), and presence of
      stress incontinence (r=-0.13; P<0.01). Analyses showed weak positive correlations
      with Black/AA (r=0.32; P<0.01), CV disease as primary ED etiology (r=0.08;
      P<0.01) and pre-operative stretched penile length (r=0.18; P<0.01). There is a
      moderate correlation with pre-operative flaccid penile length (r=0.30; P<0.01).
      Conclusions: Implanted penile prosthesis length is negatively correlated with
      some ethnic groups, prostatectomy, and incontinence. Positive correlates include
      CV disease, preoperative stretched penile length, and flaccid penile length.

PMID- 29354507
TI  - Real world treatment patterns in the neurogenic bladder population: a systematic
      literature review.
AB  - Myriad treatment modalities are available for neurogenic bladder (NGB) including
      behavioral therapies, oral pharmacotherapy, catheterization and surgical
      procedures. Little is known about how NGB patients are managed in the real world,
      how well patterns relate to clinical guidelines and how strategies may have
      changed over time. To address this gap, a systematic review (SR) was conducted
      using MEDLINE and EMBASE [1996-2017]. The inclusion criteria for studies were:
      (I) published in English; (II) conducted in human subjects; (III) reporting the
      treatment patterns/use in NGB; (IV) conducted in a real world setting. A
      narrative synthesis of results was conducted, comparing the results to current
      treatment guidelines. Percentage of treatment use was summarized using ranges.
      Eight studies met the inclusion criteria. Although most studies focused on spinal
      cord injuries (SCI), study designs and settings were heterogeneous. All data was
      collected before 2007. The most popular form of oral pharmacotherapy was
      antimuscarinics, used by 12.6-86.7% of patients; 0-100% of patients used
      catheterization techniques, 2.5-53.1% used reflex voiding (RV), and 0.2-55%
      underwent surgery. A notable amount of patients switched treatments. This SR
      revealed that numerous strategies have been used to manage NGB throughout the
      years and there has been a large variance in their use. Whilst there were some
      discrepancies, most practices matched recommendations made in current guidelines.
      Ultimately, this SR showed that there is a large gap of epidemiological studies
      conducted in the field of NGB and the authors felt that available data was
      insufficient to build a comprehensive picture of treatment patterns.
      Epidemiological studies using electronic medical records (EMRs) are necessary to
      advance our understanding of how treatment patterns have changed, and also build
      a comprehensive picture of how patients are managed in current practice.

PMID- 29354508
TI  - Seminal vesicle schwannoma presenting as rectal pain: successful robotic-assisted
      excision.
AB  - Schwannomas, not uncommon in the head and neck, rarely occur in the pelvis. Here
      we describe a seminal vesicle schwannoma, the first of its kind successfully
      excised via robotic surgery. An otherwise well 62 year-old male presented with a
      complaint of rectal pain. Colonoscopy identified a mass effect on the rectum,
      suggesting an external lesion. A computed tomography scan revealed a right
      seminal vesicle mass. Transrectal ultrasound guided biopsy returned a tissue
      diagnosis of schwannoma. To aid in operative planning, magnetic resonance imaging
      of the prostate and pelvis was obtained with and without contrast. This defined a
      5 * 4 * 4 cm3 mass abutting the right seminal vesicle without evidence of
      invasion into adjacent structures. The patient underwent an elective robotic
      assisted laparoscopic resection of the mass. Final pathology demonstrated a
      completely excised schwannoma arising from the soft tissue adherent to the right
      seminal vesicle.

PMID- 29354509
TI  - Cutting complications before cutting corners: the need for long-term outcome
      parameters in an ever-changing landscape of intracorporeal neobladder technique.

PMID- 29354510
TI  - Pure transumbilical approach for oncologic surgeries of the male pelvis is now
      closer to become a reality.

PMID- 29354511
TI  - Which is better in patients with hydronephrosis before radical cystectomy
      percutaneous nephrostomy versus internal ureteral stents.

PMID- 29354512
TI  - Next-generation sequencing in non-muscle-invasive bladder cancer-a step towards
      personalized medicine for a superficial bladder tumor.

PMID- 29354513
TI  - Double J stent prior to cystectomy increases the risk of upper urinary tract
      recurrence?

PMID- 29354514
TI  - The impact of perioperative blood transfusion on survival outcomes in radical
      cystectomy patients.

PMID- 29354515
TI  - Clients' expectations from and satisfaction with medicine retail outlets in
      Gondar town, northwestern Ethiopia: a cross-sectional study.
AB  - Purpose: The aim of this study was to assess clients' level of expectation from
      and satisfaction with medicine retail outlets (MROs) in Gondar town, northwestern
      Ethiopia. Patients and methods: An institutions-based cross-sectional study was
      conducted from April 20 to May 5, 2014, by sampling five pharmacies and eight
      drug stores through simple random sampling. Clients, 424, who came to the MROs
      during the study period were included in the study. Data were collected using
      structured questionnaires measuring expectations and satisfaction of clients
      using a Likert scale of 1-5 through face-to-face interviews. Results: Out of the
      total 424 interview encounters, 422 (99.5% response rate) questionnaires were
      included in the analysis, of which 61.1% were of males. The overall mean
      expectation of respondents toward MRO setting and services was 3.82 and that of
      satisfaction of the respondents was 3.02. More than three-quarters (76.8%) of the
      respondents expected medicines in affordable prices from MROs, but nearly half
      (44.8%) were not satisfied with it. Much more than half (58.5%) of the
      respondents were dissatisfied with the comfort and convenience of private
      counseling area. Also, nearly half (47.6%) of the respondents claimed that
      pharmacy professionals did not provide information regarding the storage
      condition of medications. There was statistically significant difference in
      overall expectation (t=2.707, P=0.007) and satisfaction (t=2.260, P=0.024) with
      the setting and services of MROs between respondents who claimed to know the
      difference between a pharmacy and a drug store and those who claimed they did
      not. Conclusion: Clients' expectation from MRO services was high, with average
      satisfaction. The overall expectation and satisfaction of the respondents toward
      MROs were lower in those who reported they did not know the difference between a
      pharmacy and a drug store than in those who claimed to know the difference.
      Supportive supervision by the town's health bureau on the MROs is recommended to
      help improve clients' satisfaction.

PMID- 29354516
TI  - Evidence-based and pragmatic steps for pharmacists to improve patient adherence.
AB  - All strategies and tools to improve the potential outcomes of medications therapy
      are a waste of time if the clients do not take their medication as prescribed.
      The aim of this paper is to help pharmacists to help their clients to improve
      outcomes of medicines based on improving their compliance to evidence-based
      pharmacotherapy. To reach a good compliance (result), you have to have agreement
      and concordance (method) between the practitioner and the client. Barriers and
      strategies for this, including identifying compliance problems and reasons for
      it, methods for improving information and communication, the client's
      participation, and responsibility for their own health, are presented mainly
      based on Cochrane reviews. Also some general pragmatic suggestions for how
      pharmacists can assist their clients the best are given.

PMID- 29354519
TI  - Limitations to the dynamics of pharmaceutical care practice among community
      pharmacists in Enugu urban, southeast Nigeria.
AB  - Background: The introduction of pharmaceutical care in Nigeria has been faced
      with many challenges in addition to limited information regarding the practice.
      Objective: This study aimed to determine the barriers encountered by community
      pharmacists in Nigeria in the provision of pharmaceutical care. Methods: A cross
      sectional descriptive survey was carried out in Enugu urban, southeast Nigeria.
      Data were collected using pretested and structured 5-point Likert scale
      questionnaires that were self-administered to the respondents. Data were analyzed
      using descriptive statistics. Results: The 78 community pharmacists comprised 62
      males and 16 females. Out of the 78 respondents, 69 (88.5%) had the basic
      Bachelor of Pharmacy degree while three (3.9%) had Fellowship, Master's, and
      Doctor of Pharmacy degrees respectively. The mean number of years of practice was
      8.2 (+/-0.6). The key limitations to the implementation of pharmaceutical care
      were: pharmacists' attitude and lack of pharmaceutical care skills, as well as
      resource and system-related constraints. Others challenges were interprofessional
      and academic obstacles like lack of collaboration (66.6%) and lack of role models
      (42.1%). Most of the respondents (81%) were strongly willing to adopt and
      implement pharmaceutical care, while 19.2% were not strongly willing to practice
      pharmaceutical care. Conclusion: Despite limitations to practice, community
      pharmacists in the area are very inclined to implement pharmaceutical care in the
      private sector to improve patients' quality of life.

PMID- 29354518
TI  - Chemotherapy e-prescribing: opportunities and challenges.
AB  - Chemotherapy drugs are characterized by low therapeutic indices and significant
      toxicities at clinically prescribed doses, raising serious issues of drug safety.
      The safety of the chemotherapy medication use process is further challenged by
      regimen complexity and need to tailor treatment to patient status. Errors that
      occur during chemotherapy prescribing are associated with serious and life
      threatening outcomes. Computerized provider order entry (CPOE) systems were shown
      to reduce overall medication errors in ambulatory and inpatient settings. The
      adoption of chemotherapy CPOE is lagging due to financial cost and cultural and
      technological challenges. Institutions that adopted infusional or oral
      chemotherapy electronic prescribing modified existing CPOE systems to allow
      chemotherapy prescribing, implemented chemotherapy-specific CPOE systems, or
      developed home-grown chemotherapy electronic prescribing programs. Implementation
      of chemotherapy electronic prescribing was associated with a significant
      reduction in the risk of prescribing errors, most significantly dose calculation
      and adjustment errors. In certain cases, implementation of chemotherapy CPOE was
      shown to improve the chemotherapy use process. The implementation of chemotherapy
      CPOE may increase the risk of new types of errors, especially if processes are
      not redesigned and adapted to CPOE. Organizations aiming to implement
      chemotherapy CPOE should pursue a multidisciplinary approach engaging all
      stakeholders to guide system selection and implementation. Following
      implementation, organizations should develop and use a risk assessment process to
      identify and evaluate unanticipated consequences and CPOE-generated errors. The
      results of these analyses should serve to further enhance the chemotherapy
      electronic prescribing process and improve the quality and safety of cancer care.

PMID- 29354517
TI  - The role of medications and their management in acute kidney injury.
AB  - Prior to 2002, the incidence of acute renal failure (ARF) varied as there was no
      standard definition. To better understand its incidence and etiology and to
      develop treatment and prevention strategies, while moving research forward, the
      Acute Dialysis Quality Initiative workgroup developed the RIFLE (risk, injury,
      failure, loss, end-stage kidney disease) classification. After continued data
      suggesting that even small increases in serum creatinine lead to worse outcomes,
      the Acute Kidney Injury Network (AKIN) modified the RIFLE criteria and used the
      term acute kidney injury (AKI) instead of ARF. These classification and staging
      systems provide the clinician and researcher a starting point for refining the
      understanding and treatment of AKI. An important initial step in evaluating AKI
      is determining the likely location of injury, generally classified as prerenal,
      renal, or postrenal. There is no single biomarker or test that definitively
      defines the mechanism of the injury. Identifying the insult(s) requires a
      thorough assessment of the patient and their medical and medication histories.
      Prerenal injuries arise primarily due to renal hypoperfusion. This may be the
      result of systemic or focal conditions or secondary to the effects of drugs such
      as nonsteroidal anti-inflammatory drugs, calcineurin inhibitors (CIs), and
      modulators of the renin-angiotensin-aldosterone system. Renal, or intrinsic,
      injury is an overarching term that represents complex conditions leading to
      considerable damage to a component of the intrinsic renal system (renal tubules,
      glomerulus, vascular structures, inter-stitium, or renal tubule obstruction).
      Acute tubular necrosis and acute interstitial nephritis are the more common types
      of intrinsic renal injury. Each type of injury has several drugs that are
      implicated as a possible cause, with antiinfectives being the most common.
      Postrenal injuries that result from obstruction block the flow of urine, leading
      to hydronephrosis and subsequent damage to the renal parenchyma. Drugs associated
      with tubular obstruction include acyclovir, methotrexate, and several
      antiretrovirals. Renal recovery from drug-induced AKI begins once the offending
      agent has been removed, if clinically possible, and is complete in most cases. It
      is uncommon that renal replacement therapy will be needed while recovery occurs.
      Pharmacists can play a pivotal role in identifying possible causes of drug
      induced AKI and limit their toxic effect by identifying those most likely to
      cause or contribute to injury. Dose adjustment is critical during changes in
      renal function, and the pharmacist can ensure that optimal therapy is provided
      during this critical time.

PMID- 29354520
TI  - Role of community pharmacists in patients' self-care and self-medication.
AB  - This review highlights the growing prominence of self-care and explores the
      contribution of community pharmacy. Firstly, background to self-care is
      discussed, followed by placing self-care in context with regard to the general
      public and accessing community pharmacy. From this perspective the contribution
      community pharmacy currently makes is assessed, paying particular attention to
      the factors that negatively impact on the ability of community pharmacy to
      facilitate self-care.

PMID- 29354521
TI  - The role of community pharmacy-based vaccination in the USA: current practice and
      future directions.
AB  - Community pharmacy-based provision of immunizations in the USA has become
      commonplace in the last few decades, with success in increasing rates of
      immunizations. Community pharmacy-based vaccination services are provided by
      pharmacists educated in the practice of immunization delivery and provide a
      convenient and accessible option for receiving immunizations. The pharmacist's
      role in immunization practice has been described as serving in the roles of
      educator, facilitator, and immunizer. With a majority of pharmacist-provided
      vaccinations occurring in the community pharmacy setting, there are many examples
      of community pharmacists serving in these immunization roles with successful
      outcomes. Different community pharmacies employ a number of different models and
      workflow practices that usually consist of a year-round in-house service staffed
      by their own immunizing pharmacist. Challenges that currently exist in this
      setting are variability in scopes of immunization practice for pharmacists across
      states, inconsistent reimbursement mechanisms, and barriers in technology. Many
      of these challenges can be alleviated by continual education; working with
      legislators, state boards of pharmacy, stakeholders, and payers to standardize
      laws; and reimbursement design. Other challenges that may need to be addressed
      are improvements in communication and continuity of care between community
      pharmacists and the patient centered medical home.

PMID- 29354522
TI  - Pharmacist interventions for obesity: improving treatment adherence and patient
      outcomes.
AB  - Obesity is currently a worldwide pandemic, with overweight (body mass index [BMI]
      >=25 kg/m2) and obesity (BMI >=30 kg/m2) estimated at 35% and 12% of the global
      adult population, respectively. According to data collected from the United
      States National Health and Nutrition Examination Survey, approximately 68.8% of
      US adults are overweight or obese. Additionally, a large burden of health care
      costs can be attributed directly to obesity as well as multiple, potentially
      preventable, comorbidities such as cancer, cardiovascular disease, and diabetes.
      As a result, national and international organizations, such as the US Centers for
      Disease Control and World Health Organization, have made halting the rise of the
      obesity epidemic a top priority. Pharmacists, commonly considered one of the most
      trustworthy and accessible health care professionals, are ideally situated to
      provide counseling for weight and lifestyle management. This review presents
      examples of pharmacist-led as well as collaborative practices that have been
      somewhat successful in educating and monitoring patient progress in attaining
      weight-loss goals. Common barriers and potential solutions to administration of
      lifestyle counseling and monitoring programs, such as limited pharmacist time and
      resources, lack of expertise and/or confidence in program administration, and
      patient perception and awareness, are also discussed.

PMID- 29354523
TI  - Big data in pharmacy practice: current use, challenges, and the future.
AB  - Pharmacy informatics is defined as the use and integration of data, information,
      knowledge, technology, and automation in the medication-use process for the
      purpose of improving health outcomes. The term "big data" has been coined and is
      often defined in three V's: volume, velocity, and variety. This paper describes
      three major areas in which pharmacy utilizes big data, including: 1) informed
      decision making (clinical pathways and clinical practice guidelines); 2) improved
      care delivery in health care settings such as hospitals and community pharmacy
      practice settings; and 3) quality performance measurement for the Centers for
      Medicare and Medicaid and medication management activities such as tracking
      medication adherence and medication reconciliation.

PMID- 29354525
TI  - Polypharmacy in pediatric patients and opportunities for pharmacists'
      involvement.
AB  - Rates of chronic conditions among pediatrics have been steadily increasing and
      medications used to treat these conditions have also shown a proportional
      increase. Most clinical trials focus on the safety of solitary medications in
      adult patients. However, data from these trials are often times extrapolated for
      use in pediatric patients who have different pharmacokinetic processes and
      physical profiles. As research increases and more drugs become available for
      pediatric use, the issue of polypharmacy becomes more of a concern. Polypharmacy
      is defined as the practice of administering or using multiple medications
      concurrently for the treatment of one to several medical disorders. With the
      increased rates of diagnosed complex disease states as prescribed mediations in
      pediatric patients, the prevalence and effect of polypharmacy in this patient
      population is largely a mystery. Polypharmacy falls within the realm of expertise
      of specialized pharmacists who can undertake medication therapy management
      services, medical chart reviews, and other services in pediatrics. Pharmacists
      have the time and knowledge to undertake pertinent interventions when managing
      polypharmacy and can play a major positive role in preventing adverse events. The
      aim of this paper is to review the literature on pediatric polypharmacy and
      provide insight into opportunities for pharmacists to help with management of
      polypharmacy. Information on adverse events, efficacy, and long-term outcomes
      with regard to growth and development of children subject to polypharmacy has yet
      to be published, leaving this realm of patient safety ripe for research.

PMID- 29354526
TI  - Promoting evidence-based practice in pharmacies.
AB  - Evidence-based medicine aims to optimize decision-making by using evidence from
      well-designed and conducted research. The concept of reliable evidence is
      essential, since the number of electronic information resources is increasing in
      parallel to the increasing number and type of drugs on the market. The decision
      making process is a complex and requires an extensive evaluation as well as the
      interpretation of the data obtained. Different sources provide different levels
      of evidence for decision-making. Not all the data have the same value as the
      evidence. Rational use of medicine requires that the patients receive "medicines
      appropriate to their clinical needs, in doses that meet their own individual
      requirements, for an adequate period of time, and at the lowest cost to them and
      their community." Pharmacists have a crucial role in the health system to
      maintain the rational use of medicine and provide pharmaceutical care to
      patients, because they are the drug experts who are academically trained for this
      purpose. The rational use of the pharmacist's workforce will improve the outcome
      of pharmacotherapy as well as decreasing the global health costs.

PMID- 29354524
TI  - Optimizing pharmacotherapy in elderly patients: the role of pharmacists.
AB  - As the world's population ages, global health care systems will face the burden
      of chronic diseases and polypharmacy use among older adults. The traditional
      tasks of medication dispensing and provision of basic education by pharmacists
      have evolved to active engagement in direct patient care and collaborative team
      based care. The care of older patients is an especially fitting mission for
      pharmacists, since the key to geriatric care often lies with management of
      chronic diseases and polypharmacy use, and preventing harmful consequences of
      both. Because most chronic conditions are treated with medications, pharmacists,
      with their extensive training in pharmacotherapy and pharmacokinetics, are in a
      unique and critical position in the management of them. Pharmacists have the
      expertise to detect, resolve, and prevent medication errors and drug-related
      problems, such as overtreatment, undertreatment, adverse drug events, and
      nonadherence. Pharmacists are also competent in critically reviewing and applying
      clinical guidelines to the care of individual patients, and in some instances
      confront the lack of data (common in older adults) to provide the best possible
      patient-centered care. The current review aimed to depict the evidence of
      geriatric pharmacy care, demonstrate current impact of pharmacists' interventions
      on older patients, survey the tools used by pharmacists to provide effective
      care, and explore their role in pharmacotherapy optimization in elders. The
      findings of the current review strongly support previous studies that showed
      positive impact of pharmacists' interventions on older patients' health-related
      outcomes. There is a clear role for pharmacists working directly or
      collaboratively to improve medication use and management in older populations.
      Therefore, in global health care systems, teams caring for elders should involve
      pharmacists to optimize pharmacotherapy.

PMID- 29354527
TI  - A prescription survey about combined use of acetylcholinesterase inhibitors and
      anticholinergic medicines in the dementia outpatient using electronic medication
      history data from community pharmacies.
AB  - Purpose: We investigated prescriptions regarding the combined use of donepezil
      hydrochloride (DPZ) and anticholinergics for elderly outpatients in Japan to
      determine the impact that combination therapy has on decreasing their cognitive
      functions. Methods: Using electronic medication records from 142 community
      pharmacies, outpatients older than 40 years of age taking DPZ, with or without
      other prescription medicines, were assessed over 6 years, beginning in 2007. We
      estimated the number of medicines administered along with DPZ, the number of
      anticholinergics administered along with DPZ, and the medicines' anticholinergic
      cognitive burden (ACB) scale cumulative score based on data from the top four
      pharmacies that filled the highest number of prescriptions for DPZ for
      outpatients with dementia in 2010. Data were gathered from records of 431
      patients; only three patients were younger than 60 years. Results: There was a
      1.94-fold increase in the number of prescriptions including DPZ over 6 years. The
      proportion of patients to whom other medicines were administered along with DPZ
      was 65.6% (n=283) and the proportion of those taking at least one anticholinergic
      agent was 24.1% (n=104). The mean number of medicines among subjects taking at
      least one anticholinergic was 5.7, and the mean cumulative ACB score for
      anticholinergics contained in these medicines was 2.6. Among 104 patients to whom
      the anticholinergics were administered along with DPZ, two outpatients taking
      urologic medicines such as oxybutynin hydrochloride or tolterodine tartrate were
      found. Conclusion: Our findings suggest that it is necessary to pay attention to
      a decline in cognitive function when prescribing multiple medicines, especially
      to elderly patients who have already been prescribed DPZ.

PMID- 29354528
TI  - Informed, tailored, and targeted pharmacy support for nurses administering
      medicines in care homes.
AB  - Care home nurses could benefit from more informed, tailored, and targeted
      pharmacy support when undertaking medicine administration. Pharmacists could use
      the principles of ethnographic research methods to inform, tailor, and target the
      medicine administration support they provide. It should be determined if existing
      pharmacy support has been informed following comprehensive observations of care
      home medicine administration.

PMID- 29354529
TI  - Pharmacist-led implementation of a vancomycin guideline across medical and
      surgical units: impact on clinical behavior and therapeutic drug monitoring
      outcomes.
AB  - Background: Vancomycin is the antibiotic of choice for the treatment of serious
      infections such as methicillin-resistant Staphylococcus aureus (MRSA).
      Inappropriate prescribing of vancomycin can lead to therapeutic failure,
      antibiotic resistance, and drug toxicity. Objective: To examine the effectiveness
      of pharmacist-led implementation of a clinical practice guideline for vancomycin
      dosing and monitoring in a teaching hospital. Methods: An observational pre-post
      study design was undertaken to evaluate the implementation of the vancomycin
      guideline. The implementation strategy principally involved education, clinical
      vignettes, and provision of pocket guidelines to accompany release of the
      guideline to the hospital Intranet. The target cohort for clinical behavioral
      change was junior medical officers, as they perform the majority of prescribing
      and monitoring of vancomycin in hospitals. Assessment measures were recorded for
      vancomycin prescribing, therapeutic drug monitoring, and patient outcomes.
      Results: Ninety-nine patients, 53 pre- and 46 post-implementation, were included
      in the study. Prescribing of a loading dose increased from 9% to 28% (P=0.02),
      and guideline adherence to starting maintenance dosing increased from 53% to 63%
      (P=0.32). Dose adjustment by doctors when blood concentrations were outside
      target increased from 53% to 71% (P=0.12), and correct timing of initial
      concentration measurement increased from 43% to 57% (P=0.23). Appropriately timed
      trough concentrations improved from 73% to 81% (P=0.08). Pre-dose (trough)
      concentrations in target range rose from 33% to 44% (P=0.10), while potentially
      toxic concentrations decreased from 32% to 21% (P=0.05) post-implementation.
      Infection cure rates for patients increased from 85% to 96% (P=0.11) after the
      guideline was implemented. Conclusion: The implementation strategy employed in
      this study demonstrated potential effectiveness, and should prompt additional
      larger studies to optimize strategies that will translate into improved clinical
      practice using vancomycin.

PMID- 29354530
TI  - Systematic literature review of hospital medication administration errors in
      children.
AB  - Objective: Medication administration is the last step in the medication process.
      It can act as a safety net to prevent unintended harm to patients if detected.
      However, medication administration errors (MAEs) during this process have been
      documented and thought to be preventable. In pediatric medicine, doses are
      usually administered based on the child's weight or body surface area. This in
      turn increases the risk of drug miscalculations and therefore MAEs. The aim of
      this review is to report MAEs occurring in pediatric inpatients. Methods: Twelve
      bibliographic databases were searched for studies published between January 2000
      and February 2015 using "medication administration errors", "hospital", and
      "children" related terminologies. Handsearching of relevant publications was also
      carried out. A second reviewer screened articles for eligibility and quality in
      accordance with the inclusion/exclusion criteria. Key findings: A total of 44
      studies were systematically reviewed. MAEs were generally defined as a deviation
      of dose given from that prescribed; this included omitted doses and
      administration at the wrong time. Hospital MAEs in children accounted for a mean
      of 50% of all reported medication error reports (n=12,588). It was also
      identified in a mean of 29% of doses observed (n=8,894). The most prevalent type
      of MAEs related to preparation, infusion rate, dose, and time. This review has
      identified five types of interventions to reduce hospital MAEs in children:
      barcode medicine administration, electronic prescribing, education, use of smart
      pumps, and standard concentration. Conclusion: This review has identified a wide
      variation in the prevalence of hospital MAEs in children. This is attributed to
      the definition and method used to investigate MAEs. The review also illustrated
      the complexity and multifaceted nature of MAEs. Therefore, there is a need to
      develop a set of safety measures to tackle these errors in pediatric practice.

PMID- 29354531
TI  - Patient views on an electronic dispensing device for prepackaged polypharmacy: a
      qualitative assessment in an ambulatory setting.
AB  - Objective: To collect opinions on medication management aids (MMAs) in general
      and on an electronic MMA (e-MMA) dispensing prepackaged polypharmacy in sealed
      pouches. Study setting: The setting involved community-dwelling older adults in
      Basel, Switzerland, in 2013. Study design: The study involved 1) a 14-day trial
      with the e-MMA and 2) a focus group to identify general attributes of MMAs, their
      applicability to the e-MMA, and possible target groups for the e-MMA. Data
      collection methods: Six participants using long-term polypharmacy and willing to
      try new technologies completed the 14-day trial and participated in the focus
      group. Inductive content analysis was performed to extract data. Principal
      findings: Participants rated ten of 17 general attributes as clearly applicable
      to the e-MMA and five as unsuitable. Attributes pertained to three interrelating
      themes: product design, patient support, and living conditions. Envisaged target
      groups were patients with time-sensitive medication regimens, patients with
      dementia, the visually impaired, and several patients living together to prevent
      accidental intake of the wrong medication. Conclusion: The evaluated e-MMA for
      prepackaged polypharmacy met the majority of the requirements set for an MMA.
      Patients' living conditions, such as mobility, remain the key determinants for
      acceptance of an e-MMA.

PMID- 29354533
TI  - A systematic review of the nature of dispensing errors in hospital pharmacies.
AB  - Background: Dispensing errors are common in hospital pharmacies. Investigating
      dispensing errors is important for identifying the factors involved and
      developing strategies to reduce their occurrence. Objectives: To review published
      studies exploring the incidence and types of dispensing errors in hospital
      pharmacies and factors contributing to these errors. Methods: Electronic
      databases including PubMed, Scopus, Ovid, and Web of Science were searched for
      articles published between January 2000 and January 2015. Inclusion criteria
      were: studies published in English, and studies investigating type, incidence and
      factors contributing to dispensing errors in hospital pharmacies. One researcher
      searched for all relevant published articles, screened all titles and abstracts,
      and obtained complete articles. A second researcher assessed the titles,
      abstracts, and complete articles to verify the reliability of the selected
      articles. Key findings: Fifteen studies met the inclusion criteria all of which
      were conducted in just four countries. Reviewing incident reports and direct
      observation were the main methods used to investigate dispensing errors.
      Dispensing error rates varied between countries (0.015%-33.5%) depending on the
      dispensing system, research method, and classification of dispensing error types.
      The most frequent dispensing errors reported were dispensing the wrong medicine,
      dispensing the wrong drug strength, and dispensing the wrong dosage form. The
      most common factors associated with dispensing errors were: high workload, low
      staffing, mix-up of look-alike/ sound-alike drugs, lack of knowledge/experience,
      distractions/interruptions, and communication problems within the dispensary
      team. Conclusion: Studies relating to dispensing errors in hospital pharmacies
      are few in number and have been conducted in just four countries. The majority of
      these studies focused on the investigation of dispensing error types with no
      mention of contributing factors or strategies for reducing dispensing errors.
      Others studies are thus needed to investigate dispensing errors in hospital
      pharmacies, and a combined approach is recommended to investigate contributing
      factors associated with dispensing errors and explore strategies for reducing
      these errors.

PMID- 29354534
TI  - Chronic care model in primary care: can it improve health-related quality of
      life?
AB  - Purpose: Chronic diseases such as hypertension, diabetes mellitus, and
      hyperlipidemia are public health concerns. However, little is known about how
      these affect patient-level health measures. The aim of the study was to examine
      the impact of a chronic care model (CCM) on the participant's health-related
      quality of life (QoL). Patients and methods: Participants received either usual
      care or CCM by a team of health care professionals including pharmacists, nurses,
      dietitians, and general practitioners. The participants in the intervention group
      received medication counseling, adherence, and dietary advice from the health
      care team. The QoL was measured using the EQ-5D (EuroQoL-five dimension, health
      related quality of life questionnaire) and comparison was made between usual care
      and intervention groups at the beginning and end of the study at 6 months.
      Results: Mean (standard deviation) EQ-5D index scores improved significantly in
      the intervention group (0.92+/-0.10 vs 0.95+/-0.08; P<=0.01), but not in the
      usual care group (0.94+/-0.09 vs 0.95+/-0.09; P=0.084). Similarly, more
      participants in the intervention group reported improvements in their QoL
      compared with the usual care group, especially in the pain/discomfort and
      anxiety/depression dimensions. Conclusion: The implementation of the CCM resulted
      in significant improvement in QoL. An interdisciplinary team CCM approach should
      be encouraged, to ultimately result in behavior changes and improve the QoL of
      the patients.

PMID- 29354532
TI  - Improving medication adherence: a framework for community pharmacy-based
      interventions.
AB  - Evidence supports that patient medication adherence is suboptimal with patients
      typically taking less than half of their prescribed doses. Medication
      nonadherence is associated with poor health outcomes and higher downstream health
      care costs. Results of studies evaluating pharmacist-led models in a community
      pharmacy setting and their impact on medication adherence have been mixed.
      Community pharmacists are ideally situated to provide medication adherence
      interventions, and effective strategies for how they can consistently improve
      patient medication adherence are necessary. This article suggests a framework to
      use in the community pharmacy setting that will significantly improve patient
      adherence and provides a strategy for how to apply this framework to develop and
      test new medication adherence innovations. The proposed framework is composed of
      the following elements: 1) defining the program's pharmacy service vision, 2)
      using evidence-based, patient-centered communication and intervention strategies,
      3) using specific implementation approaches that ensure fidelity, and 4) applying
      continuous evaluation strategies. Within this framework, pharmacist interventions
      should include those services that capitalize on their specific skill sets. It is
      also essential that the organization's leadership effectively communicates the
      pharmacy service vision. Medication adherence strategies that are evidence-based
      and individualized to each patient's adherence problems are most desirable.
      Ideally, interventions would be delivered repeatedly over time and adjusted when
      patient's adherence circumstances change. Motivational interviewing principles
      are particularly well suited for this. Providing effective training and ensuring
      that the intervention can be delivered with fidelity within a specified workflow
      process are also essential for success. Utilizing this proposed framework will
      lead to greater and consistent success when implementing pharmacist-led
      medication adherence interventions in the community pharmacy setting.

PMID- 29354535
TI  - Community pharmacy: an untapped patient data resource.
AB  - As community pharmacy services become more patient centered, they will be
      increasingly reliant on access to good quality patient information. This review
      describes how the information that is currently available in community pharmacies
      can be used to enhance service delivery and patient care. With integration of
      community pharmacy and medical practice records on the horizon, the opportunities
      this will provide are also considered. The community pharmacy held patient
      medication record, which is the central information repository and has been used
      to identify non-adherence, prompts the pharmacist to clinically review
      prescriptions, identify patients for additional services, and identify those
      patients at greater risk of adverse drug events. While active recording of
      patient consultations for treatment over the counter may improve the quality of
      consultations and information held, the lost benefits of anonymity afforded by
      community pharmacies need to be considered. Recording of pharmacy staff
      activities enables the workload to be monitored, remuneration to be justified,
      critical incidents to be learned from, but is not routine practice.
      Centralization of records between community pharmacies enables practices to be
      compared and consistent problems to be identified. By integrating pharmacy and
      medical practice records, patient behavior with respect to medicines can be more
      closely monitored and should prevent duplication of effort. When using patient
      information stored in a community pharmacy, it is, however, important to consider
      the reason why the information was recorded in the first instance and whether it
      is appropriate to use it for a different purpose without additional patient
      consent. Currently, community pharmacies have access to large amounts of
      information, which, if stored and used appropriately, can significantly enhance
      the quality of provided services and patient care. Integrating the records
      increases opportunities to enhance patient care yet further. While community
      pharmacies have significant amounts of information available to them, this is
      frequently untapped.

PMID- 29354536
TI  - Community pharmacists provided telephone treatment support for patients who
      received long-term prescribed medication.
AB  - Purpose: This study was conducted to evaluate whether a community pharmacist's
      assistance during the treatment of a patient with a chronic illness would help to
      discover and improve issues regarding the treatment. Method: We employed a
      prospective intervention study with a control group. The patients ranging in age
      from 60 to 74, were using one of the six selected community pharmacies in the
      Tokyo metropolitan area. They had been prescribed six or fewer kinds of
      medications, one of which was amlodipine. The medication dosages covered 1 month
      or longer. Patients who agreed to participate in the study were randomly assigned
      to the groups at each pharmacy. For the patients in the intervention group, the
      pharmacists provided telephone counseling between physician visits, in addition
      to the time they visited the pharmacies to collect their medications. For the
      patients in the control group, the pharmacists provided counseling only at their
      pharmacies. Results and discussion: The average days of medication administration
      were 49.2 days for the 58 patients in the intervention group, and 49.8 days for
      the 53 patients in the control group, with the average number of medications
      being 3.4 items per person for both groups. Through the telephone counseling, we
      were able to collect more information, eg, changes in physical condition and
      occurrences of side effects, from the intervention group than from the control
      group. The rate of incident detection in the information from the intervention
      group was five times that of the control group, making subsequent incident
      resolutions faster. Conclusion: This study suggested that phone counseling
      between physician visits could enable the identification of more issues regarding
      patients' conditions.

PMID- 29354537
TI  - Causes and consequences of e-prescribing errors in community pharmacies.
AB  - Major national policy forces are promoting the adoption and use of health
      information technology (health IT) to improve the quality, safety, and efficiency
      of health care delivery. One such health IT is electronic prescribing (e
      prescribing), which is the direct transmission of prescription information from a
      provider to a pharmacy. Given research showing that handwritten prescriptions are
      unsafe and associated errors can lead to tremendous inefficiency for patients and
      pharmacists, e-prescribing has many potential benefits. However, as with the
      introduction of any new technology, unintended, adverse consequences may result.
      The purpose of this review is to explore the causes and consequences of e
      prescribing errors in community pharmacies, which are pharmacies not affiliated
      with a hospital or clinic. Many new types of errors - including provider order
      entry errors, transcription errors, and dispensing errors - appear to result from
      e-prescribing. These lead to important consequences for pharmacies, including
      safety threats to patients, reduced efficiency for pharmacists, processing
      delays, and increased pharmacy cost. Increased attention to system design and
      pharmacist training, as well as additional research in this area, will be
      critical to realize the full benefits of e-prescribing.

PMID- 29354538
TI  - The future of pain pharmacy: driven by need.
AB  - Background: Opioid prescribing has increased by ~400% over the past 20 years in
      the US and has been correlated with dramatic increases in accidental overdose
      related deaths. Emerging evidence of serious dose-dependent side effects of
      opioid analgesics has led to recommendations from multinational pain societies
      and governments to decrease opioid doses and increase referrals to pain
      specialists. Demand for pain specialists of all types has increased; however,
      training programs for health care professionals struggle to satisfy this need.
      Objective: The purpose of this article is to highlight the role of clinical
      pharmacy specialists in pain management and to discuss available residency
      training programs and subspecialties within each program. Methods: We surveyed
      all eleven accredited pharmacy postgraduate year two (PGY-2) Pain and Palliative
      Care Residency programs in the US. Program information was derived from
      interviews with residency directors, current residents, program brochures, and
      residency Web sites. Data collected included core, elective, and longitudinal
      rotations, with the time frame dedicated to each experience. Primary practice
      areas, as well as inpatient vs outpatient focus, were also documented.
      Additionally, a review of the available literature was completed to determine the
      areas in greatest need for future pain specialists. Results: Pharmacy pain
      specialists have been referenced as highly effective additions to
      interdisciplinary pain management teams. Pharmacists provide expertise in complex
      pain medication management, which remains the primary focus of most chronic pain
      encounters. The PGY-2 programs surveyed differ considerably, with the majority
      providing significant emphasis to either acute pain management or palliative care
      with brief or limited exposure to chronic pain management. Four of the eleven
      programs require 2 months of chronic pain management; however, only two of the
      eleven programs identify chronic pain management as a primary practice setting.
      Discussion: Pain specialists in all fields are in high demand; however, the need
      for health care professionals specialized in chronic pain management probably
      exceeds that for professionals specialized in acute pain management and
      palliative care combined. This disparity between disease prevalence and specialty
      training programs is not reflected in the current residency training structure,
      nor have additional training programs arisen to fill this critical need.
      Conclusion: Health care systems will continue to struggle to meet the demands of
      patients with chronic pain until significant emphasis is placed on the education
      and training of health care professionals in this area. Clinical pharmacy should
      aim to meet this demand through the expansion of PGY-2 training programs and
      improved didactic education in pharmacy school that reflects the increased need
      for chronic pain specialists.

PMID- 29354539
TI  - Optimizing care transitions: the role of the community pharmacist.
AB  - Transitions of care (TOC) refer to the movement of patients across institutions,
      among providers, between different levels of care, and to and from home.
      Medication errors that occur during TOC have the potential to result in medical
      complications that are serious for the patient and costly to the health care
      system. Positive outcomes have been demonstrated when pharmacists are involved in
      providing TOC services, including reducing preventable adverse drug reactions,
      medication-related problems, and rehospitalizations, as well as improving the
      discharge process. This review explores TOC models involving community pharmacy
      practice, the current impact of pharmacist interventions in TOC, and patient
      satisfaction with TOC services provided by community pharmacists. Common barriers
      and potential solutions to TOC services provided in the community pharmacy, such
      as patient identification, information gathering, standardization of services,
      administrative support, reimbursement, and time restraints, are also discussed.

PMID- 29354540
TI  - Clinical impact of a pharmacist-led inpatient anticoagulation service: a review
      of the literature.
AB  - Background: Anticoagulant therapies provide management options for potentially
      life-threatening thromboembolic conditions. They also carry significant safety
      risks, requiring careful consideration of medication dose, close monitoring, and
      follow-up. Inpatients are particularly at risk, considering the widespread use of
      anticoagulants in hospitals. This has prompted the introduction of safety goals
      for anticoagulants in Canada and the USA, which recommend increased pharmacist
      involvement to reduce patient harm. The goal of this review is to evaluate the
      efficacy and safety of pharmacist-led inpatient anticoagulation services compared
      to usual or physician-managed care. Methods: This narrative review includes
      articles identified through a literature search of PubMed, Embase, and
      International Pharmaceutical Abstracts databases, as well as hand searches of the
      references of relevant articles. Full publications of pharmacist-managed
      inpatient anticoagulation services were eligible if they were published in
      English and assessed clinical outcomes. Results: Twenty-six studies were included
      and further divided into two categories: 1) autonomous pharmacist-managed
      anticoagulation programs (PMAPs) and 2) pharmacist recommendation. Pharmacist
      management of heparin and warfarin appears to result in improvements in some
      surrogate outcomes (international normalized ratio [INR] stability and time in
      INR goal range), while results for others are mixed (time to therapeutic INR,
      length of stay, and activated partial thromboplastin time [aPTT] measures). There
      is also some indication that PMAPs may be associated with reduced patient
      mortality. When direct thrombin inhibitors are managed by pharmacists, there
      seems to be a shorter time to therapeutic aPTT and a greater percentage of time
      in the therapeutic range, as well as a decrease in the frequency of medication
      errors. Pharmacist recommendation services have generally resulted in a greater
      time in therapeutic INR range, greater INR stability, decreased length of stay,
      and reduced major drug interactions, with no significant differences in safety
      outcomes. Conclusion: Pharmacist-led inpatient anticoagulation management seems
      to result in superior outcomes, as compared to usual or physician-managed care.
      This conclusion is limited by small, poorly designed studies lacking statistical
      power, focusing mainly on surrogate outcomes.

PMID- 29354541
TI  - Prescription opioid abuse: pharmacists' perspective and response.
AB  - Opioid medication abuse and overdose are major concerns for public health, and a
      number of responses to address these issues have taken place across the US.
      Pharmacists and the pharmacy profession have made important contributions as a
      part of the response to this national crisis. This article provides a brief
      review of the antecedents, driving forces, and health status of patients involved
      in the opioid medication and overdose epidemic. This review further discusses
      pharmacy-based actions that have been undertaken to address this issue, including
      prescription drug monitoring, take-back, and naloxone training/distribution
      programs. This review likewise examines current efforts underway in the field to
      educate practitioners and needed future steps that must be taken by pharmacists
      in order to continue the profession's pivotal role in working toward resolving
      this national public health problem. In particular, evidence and arguments are
      presented for proactively identifying and intervening with patients who abuse
      and/or are at risk for overdose. Continued and active engagement by pharmacists
      in these efforts has the potential to result in important reductions in opioid
      medication abuse and overdose and improvements for patient's health.

PMID- 29354543
TI  - Erratum: Telepharmacy: a pharmacist's perspective on the clinical benefits and
      challenges [Corrigendum].
AB  - [This corrects the article on p. 75 in vol. 5.].

PMID- 29354542
TI  - Telepharmacy: a pharmacist's perspective on the clinical benefits and challenges.
AB  - The use of information and telecommunication technologies has expanded at a rapid
      rate, which has a strong influence on healthcare delivery in many countries.
      Rural residents and communities, however, often lack easy access to healthcare
      services due to geographical and demographical factors. Telepharmacy, a more
      recent concept that refers to pharmaceutical service provision, enables
      healthcare services, such as medication review, patients counseling, and
      prescription verification, by a qualified pharmacist for the patients located at
      a distance from a remotely located hospital, pharmacy, or healthcare center.
      Telepharmacy has many recognizable benefits such as the easy access to healthcare
      services in remote and rural locations, economic benefits, patient satisfaction
      as a result of medication access and information in rural areas, effective
      patient counseling, and minimal scarcity of local pharmacist and pharmacy
      services. Telepharmacy undoubtedly is a great concept, but it is sometimes
      challenging to put into practice. Inherent to the adoption of these practices are
      legal challenges and pitfalls that need to be addressed. The start-up of
      telepharmacy (hardware, software, connectivity, and operational cost) involves
      considerable time, effort, and money. For rural hospitals with fewer patients,
      the issue of costs appears to be one of the biggest barriers to telepharmacy
      services. Moreover, execution and implementation of comprehensive and uniform
      telepharmacy law is still a challenge. A well-developed system, however, can
      change the practice of pharmacy that is beneficial to both the rural communities
      and the hospitals or retail pharmacies that deliver these services.

PMID- 29354544
TI  - Clients' perception and satisfaction toward service provided by pharmacy
      professionals at a teaching hospital in Ethiopia.
AB  - Background: Evaluation of client's perception and satisfaction with pharmacy
      services is important to identify specific areas of the service that need
      improvement in achieving high-quality pharmacy services. It also helps to detect
      the gaps in the current pharmaceutical services provision. Objective: To assess
      clients' perception and satisfaction toward service provided by pharmacy
      professionals at Mizan-Tepi University Teaching Hospital. Methods: A cross
      sectional study design was employed from March 8 to 24, 2016. A semistructured
      questionnaire was used to assess clients' perception and satisfaction toward
      service provided by pharmacy professionals. The data collected were entered into
      Epi data 3.1, cleaned, and transported into and analyzed using SPSS version 20.
      Logistic regression was employed to determine associated factors, and statistical
      significance was considered at p-value <0.05. Results: Among 384 respondents,
      53.1% were male. Of the total participants, 63.8% had good perception and 36.2%
      had poor perception toward pharmacy services. With regard to satisfaction, 52.6%
      of the respondents were satisfied and 47.4% were unsatisfied by the
      pharmaceutical services. Sociodemographic variables such as educational level
      (p=0.000), occupation (p=0.031), payment for service (p=0.002), and reasons the
      respondents seek service (p=0.001) showed statistically significant association
      with the level of perception. Clients' satisfaction was found to be significantly
      associated with educational level (p=0.002) and reason for seeking service
      (p=0.016). Conclusion and recommendation: This study showed that the overall mean
      perception and satisfaction of clients in Mizan-Tepi University Teaching Hospital
      was low, even though it was above the mean level of perception and satisfaction.
      Action has to be taken to improve the perception and satisfaction of clients with
      the services provided in the pharmacy section.

PMID- 29354545
TI  - Abuse of over-the-counter medicines: a pharmacist's perspective.
AB  - Self-care and self-medication practices are essential components of any health
      care systems. The use of over-the-counter (OTC) medications is a part of the self
      medication process. The popularity of OTC medication use among patients may
      increase the abuse potential of OTC medications. With pharmacists being as
      accessible as they are, they are often the first line of contact for patients,
      and have the opportunity to educate and counsel patients on appropriate OTC
      medication use. The presence of a pharmacist ensures safe and effective use of
      OTC medications. Pharmacists can liaise with other health care providers in the
      management of self-care practices by patients. However, a pharmacist has
      traditionally been underutilized in this role. This article provides a brief
      review on OTC medications with abuse potential and the effect of self-medication
      on OTC medication abuse. This review further describes the barriers faced by
      pharmacists in OTC medication abuse management, given the increased potential of
      prescription-to-OTC switch in recent years. In addition, the potential for a
      behind-the-counter drug category to boost patient-pharmacist interaction was
      discussed. The current review supports the positive role played by pharmacists in
      the management of OTC medication abuse. This review adds to the knowledge base of
      the barriers faced by pharmacists to prevent OTC medication abuse while
      developing appropriate intervention strategies. By expanding the role of
      pharmacists, OTC medication abuse may be controlled more effectively, thereby
      providing better patient medication therapy management and outcomes.

PMID- 29354546
TI  - Benefit of hospital pharmacy intervention on the current status of dry powder
      inhaler technique in patients with asthma and COPD: a study from the Central
      Development Region, Nepal.
AB  - Background: The majority of patients with asthma and chronic obstructive
      pulmonary disease (COPD) have been known to perform inhaler technique
      inadequately. We aimed to evaluate the benefit of hospital pharmacy intervention
      on the current status of dry powder inhaler (Rotahaler(r)) technique in such
      patients and the factors associated with the correct use. Methods: A pre-post
      interventional study was conducted at the outpatient pharmacy in a teaching
      hospital of the Central Development Region, Nepal, in patients with asthma and
      COPD currently using a Rotahaler device. Patients' demographics and Rotahaler
      technique were assessed before intervention. Those who failed to demonstrate the
      correct technique were educated and trained by the pharmacist, and their
      technique was reassessed after 2 weeks of intervention. Descriptive statistics,
      including Wilcoxon signed rank test, Mann-Whitney U test, Spearman's correlations
      and Kruskal-Wallis test, were performed for statistical analysis. Results: Before
      intervention, only 5.7% (10 of 174) of the patients demonstrated the correct
      Rotahaler technique and the most common errors observed were failure to breathe
      out gently before inhalation (98.8%) and failure to hold breath for about 10
      seconds after inhalation (84.8%). After the intervention (n=164), 67.1% of the
      patients showed their technique correctly (p<=0.001) and failure to breathe out
      gently before inhalation was the most common error (27.44%). Age (p=0.003),
      previous instruction (p=0.007), patient's education level (p=0.013) and source of
      instruction (p<0.001) were associated with an appropriate technique before
      intervention, while age (p=0.024), duration of therapy (p=0.010) and gender
      (p=0.008) were the factors correlated with correct usage after intervention.
      Conclusion: The current status of Rotahaler technique is inadequate in patients
      with asthma and COPD attending the Chitwan Medical College Teaching Hospital in
      the Central Development Region, Nepal. However, a single hospital pharmacy
      intervention can significantly improve the correct use of the technique,
      highlighting the role of hospital pharmacies in the improvement of inhaler
      technique.

PMID- 29354547
TI  - The role of the pharmacist in the management of type 2 diabetes: current insights
      and future directions.
AB  - Type 2 diabetes is a chronic disease occurring in ever increasing numbers
      worldwide. It contributes significantly to the cost of health globally; however,
      its management remains in the most part less than optimal. Patients must be
      empowered to self-manage their disease, and they do this in partnership with
      health care professionals. Whilst the traditional role of the pharmacist has been
      centered around the supply of medicines and patient counseling, there is an
      evergrowing body of evidence that pharmacists, through a range of extended
      services, may contribute positively to the clinical and humanistic outcomes of
      those with diabetes. Further, these services can be delivered cost-effectively.
      This paper provides a review of the current evidence supporting the role of
      pharmacists in diabetes care, whilst providing a commentary of the future roles
      of pharmacists in this area.

PMID- 29354548
TI  - Antihypertensive drug prescription patterns and their impact on outcome of blood
      pressure in Ethiopia: a hospital-based cross-sectional study.
AB  - Background: Irrational prescription is strongly associated with poor control of
      hypertension. The present study aimed to evaluate antihypertensive drug
      prescription trends and to measure their impact on the level of blood pressure
      (BP) control in Gondar University Hospital, Gondar, Ethiopia. Methods: A hospital
      based retrospective cross-sectional study was conducted from May 30 to June 30,
      2016. All hypertensive patients on medication were included. A structured data
      abstraction form was prepared to gather the necessary information. The
      prescription patterns and BP level were measured retrospectively. A binary
      logistic regression was computed to determine the effect of different
      prescription patterns on BP control. Results: A total of 596 hypertension
      patients were recruited for the study; of them, 561(94%) met the study criteria.
      The mean age of the respondents was 55.96+/-14.6 years. Females constituted 58.2%
      of the study population. Approximately fifty percent of the prescriptions were
      monotherapies. Twice-daily dosing was associated with lower risk of uncontrolled
      hypertension (crude odds ratio [COR] =0.51[0.15-0.73], adjusted odds ratio [AOR]
      =0.69[0.163-0.91]). Monthly appointment was linked with a nearly 90% reduced
      incidence of uncontrolled BP (COR =0.15[0.04-0.73], AOR =0.093[0.024-0.359]).
      Conclusion: Monotherapies were the most frequently prescribed regimens. Twice
      daily dosing and monthly appointments were associated with low incidence of
      uncontrolled BP. Clinicians should be vigilant in adjusting the frequency of
      dosing and should fix appointment date in consultation with their patients.

PMID- 29354550
TI  - Prevalence of intravenous medication administration errors: a cross-sectional
      study.
AB  - Background: Intravenous medication administration errors (MAEs) may be
      accompanied by avoidable undesirable effects, which might result in clinical
      complications. Objective: The aim of the study was to determine the prevalence of
      MAEs and to identify the factors associated with such errors. Methods: A hospital
      based cross-sectional study was conducted from March to April 2015. Data were
      collected by direct observation using a pretested data collection tool. Simple
      random sampling was used, and bivariate logistic regression model was used to
      identify the factors associated with MAEs. P value <0.05 was considered
      statistically significant. Results: A total of 134 patients were found to be
      eligible for the study. More than half of the study participants were males (76
      [56.7%]). The rate of MAE was 46.1%, with the missed dose (n=162, 95.8%) being
      reported as the most common error. The age groups of 60-79 years (adjusted odds
      ratio = 2.166, confidence interval = 1.532-8.799) and 80-101 years (adjusted odds
      ratio = 1.52, confidence interval = 1.198-5.584) were the determinants of MAEs.
      Conclusion: A high prevalence of MAEs was found. Enhancing the knowledge and
      practical skills of clinical nurses might minimize such errors.

PMID- 29354549
TI  - Role of the pharmacist in reducing healthcare costs: current insights.
AB  - Global healthcare expenditure is escalating at an unsustainable rate. Money spent
      on medicines and managing medication-related problems continues to grow. The high
      prevalence of medication errors and inappropriate prescribing is a major issue
      within healthcare systems, and can often contribute to adverse drug events, many
      of which are preventable. As a result, there is a huge opportunity for
      pharmacists to have a significant impact on reducing healthcare costs, as they
      have the expertise to detect, resolve, and prevent medication errors and
      medication-related problems. The development of clinical pharmacy practice in
      recent decades has resulted in an increased number of pharmacists working in
      clinically advanced roles worldwide. Pharmacist-provided services and clinical
      interventions have been shown to reduce the risk of potential adverse drug events
      and improve patient outcomes, and the majority of published studies show that
      these pharmacist activities are cost-effective or have a good cost:benefit ratio.
      This review demonstrates that pharmacists can contribute to substantial
      healthcare savings across a variety of settings. However, there is a paucity of
      evidence in the literature highlighting the specific aspects of pharmacists' work
      which are the most effective and cost-effective. Future high-quality economic
      evaluations with robust methodologies and study design are required to
      investigate what pharmacist services have significant clinical benefits to
      patients and substantiate the greatest cost savings for healthcare budgets.

PMID- 29354551
TI  - Community pharmacy COPD services: what do researchers and policy makers need to
      know?
AB  - COPD is a leading cause of morbidity and mortality across the world and is
      responsible for a disproportionate use of health care resources. It is a
      progressive condition that is largely caused by smoking. Identification of early
      stage COPD provides an opportunity for interventions, such as smoking cessation,
      which prevent its progression. Once diagnosed, ongoing support services
      potentially provide an opportunity to assist the patient in managing their
      condition and working more closely with the rest of the primary care team. While
      there are a number of robust studies which have demonstrated the role which
      pharmacists could undertake to identify and prevent disease progression, adoption
      of such services is currently limited. As a service that would seem to be
      appropriate for adoption in all societies where smoking is prevalent, we have
      performed a review of reported approaches that have been used when setting up and
      evaluating such services, and therefore aim to inform researchers and policy
      makers in other countries on how best to proceed. Implementation science has been
      used to further contextualize the findings of the review in terms of components
      that are likely to enhance the likelihood of implementation. With reference to
      screening services, we have made clear recommendations as to the identification
      of patients, structure and smoking cessation elements of the program. Further
      work needs to be undertaken by policy makers to determine the approaches that can
      be used to motivate pharmacists to provide this service. In terms of ongoing
      support services, there is some evidence to suggest that these would be effective
      and cost-effective to the health service in which they are implemented. However,
      the capability, opportunity and motivation of pharmacists to provide these, more
      complex, services need to be the focus for researchers before implementation by
      policy makers.

PMID- 29354552
TI  - Preventing drug-related adverse events following hospital discharge: the role of
      the pharmacist.
AB  - Transition of care (ToC) points, and in particular hospital admission and
      discharge, can be associated with an increased risk of adverse drug events (ADEs)
      and other drug-related problems (DRPs). The growing recognition of the pharmacist
      as an expert in medication management, patient education and communication makes
      them well placed to intervene. There is evidence to indicate that the inclusion
      of pharmacists in the health care team at ToC points reduces ADEs and DRPs and
      improves patient outcomes. The objectives of this paper are to outline the
      following using current literature: 1) the increased risk of medication-related
      problems at ToC points; 2) to highlight some strategies that have been successful
      in reducing these problems; and 3) to illustrate how the role of the pharmacist
      across all facets of care can contribute to the reduction of ADEs, particularly
      for patients at ToC points.

PMID- 29354553
TI  - Clinical relevancy and determinants of potential drug-drug interactions in
      chronic kidney disease patients: results from a retrospective analysis.
AB  - Background: Chronic kidney disease (CKD) alters the pharmacokinetic and
      pharmacodynamic responses of various renally excreted drugs and increases the
      risk of drug-related problems, such as drug-drug interactions. Objectives: To
      assess the pattern, determinants, and clinical relevancy of potential drug-drug
      interactions (pDDIs) in CKD patients. Materials and methods: This study
      retrospectively reviewed medical charts of all CKD patients admitted in the
      nephrology unit of a tertiary care hospital in Pakistan from January 2013 to
      December 2014. The Micromedex Drug-Reax(r) system was used to screen patient
      profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical
      analysis. Results: We evaluated 209 medical charts and found pDDIs in nearly
      78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8%
      patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had
      contraindicated interactions. Among those interactions, 49.4% had good evidence,
      44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed
      onset of action. The potential adverse outcomes of pDDIs included postural
      hypotension, QT prolongation, ceftriaxone-calcium precipitation, cardiac
      arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs
      was found strongly associated with the age of <60 years, number of prescribed
      medicines >=5, hypertension, and the lengthy hospitalization of patients.
      Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed
      that CKD patients with an older age, higher number of prescribed medicines,
      lengthy hospitalization, and hypertension were at a higher risk of pDDIs.

PMID- 29354554
TI  - Review of community pharmacy services: what is being performed, and where are the
      opportunities for improvement?
AB  - Objective: The aim of this review was to assess pharmacist and pharmacy services
      being provided and identify opportunities to improve patient satisfaction.
      Methods: Studies published between January 2006 and July 2016 examining patient
      satisfaction with pharmacy and pharmacist services, which were written in
      English, were identified in PubMed. Studies were excluded if they only looked at
      pharmacy student-provided services. Key findings: A total of 50 studies were
      ultimately included in the review. Of these studies, 28 examined services
      traditionally provided by community pharmacists such as dispensing and
      counseling, while 16 examined a new in-person service being offered by a
      pharmacy, and the remaining six involved a new technology-assisted service. While
      study findings were generally positive for patient satisfaction of pharmacy
      services, several opportunities were identified for pharmacies to improve.
      Conclusion: Overall, patient satisfaction is high across pharmacy services;
      however, this satisfaction is related to prior patient exposure to services and
      their level of expectation. Pharmacists have multiple opportunities to improve
      the services they provide, and there are additional services pharmacists may
      consider offering to expand their role within the health care system.

PMID- 29354555
TI  - Pharmacovigilance: pharmacists' perspective on spontaneous adverse drug reaction
      reporting.
AB  - Globally, adverse drug reactions (ADRs), one of the leading causes of morbidity
      and mortality, will continue to pose a threat to public health as long as drugs
      are being used to treat various ailments. Prompt ADR reporting is crucial in
      ensuring drug safety. The aim of this narrative review was to highlight the role
      of pharmacists in pharmacovigilance and to identify barriers and facilitators
      toward ADR reporting documented in the literature. The perspective of pharmacy
      students on pharmacovigilance and ADR reporting has also been discussed with an
      aim to highlight the need to improve content related to ADR reporting and
      pharmacovigilance in undergraduate pharmacy curriculum. Globally, although the
      role of pharmacists within national pharmacovigilance systems varies, it is very
      well recognized. In general, pharmacists acknowledge that ADR reporting is part
      of their professional responsibility and have a positive attitude toward
      reporting ADRs. However, current research evidence suggests that there are still
      critical knowledge gaps with regard to ADR reporting among pharmacists,
      especially in countries where the role of pharmacists within the health care
      system is limited. These knowledge gaps can be fulfilled through continuous
      professional development programs and reinforcing theoretical and practical
      knowledge in undergraduate pharmacy curriculums. Without adequately identifying
      and fulfilling training needs of pharmacists and other health care professionals,
      the efficiency of national pharmacovigilance systems is unlikely to improve which
      may compromise patient's safety.

PMID- 29354556
TI  - Role of the community pharmacist in emergency contraception counseling and
      delivery in the United States: current trends and future prospects.
AB  - Women and couples continue to experience unintended pregnancies at high rates. In
      the US, 45% of all pregnancies are either mistimed or unwanted. Mishaps with
      contraceptives, such as condom breakage, missed pills, incorrect timing of patch
      or vaginal ring application, contraceptive nonuse, forced intercourse, and other
      circumstances, place women at risk of unintended pregnancy. There is a critical
      role for emergency contraception (EC) in preventing those pregnancies. There are
      currently three methods of EC available in the US. Levonorgestrel EC pills have
      been available with a prescription for over 15 years and over-the-counter since
      2013. In 2010, ulipristal acetate EC pills became available with a prescription.
      Finally, the copper intrauterine device remains the most effective form of EC.
      Use of EC is increasing over time, due to wider availability and accessibility of
      EC methods. One strategy to expand access for both prescription and
      nonprescription EC products is to include pharmacies as a point of access and
      allow pharmacist prescribing. In eight states, pharmacists are able to prescribe
      and provide EC directly to women: levonorgestrel EC in eight states and
      ulipristal acetate in seven states. In addition to access with a prescription
      written by a pharmacist or other health care provider, levonorgestrel EC is
      available over-the-counter in pharmacies and grocery stores. Pharmacists play a
      critical role in access to EC in community pharmacies by ensuring product
      availability in the inventory, up-to-date knowledge, and comprehensive patient
      counseling. Looking to the future, there are opportunities to expand access to EC
      in pharmacies further by implementing legislation expanding the pharmacist scope
      of practice, ensuring third-party reimbursement for clinical services delivered
      by pharmacists, and including EC in pharmacy education and training.

PMID- 29354557
TI  - Overcoming barriers to intranasal corticosteroid use in patients with
      uncontrolled allergic rhinitis.
AB  - Patients suffering from allergic rhinitis often attempt to self-manage their
      symptoms and may seek advice from pharmacists about nonprescription product
      choices. Several drug classes, both prescription and over-the-counter (OTC), are
      available, including intranasal corticosteroids (INCSs); oral, intranasal, and
      ocular antihistamines; leukotriene antagonists; and topical and systemic
      decongestants, as well as immunotherapies. Selection of the optimal treatment
      approach depends on the temporal pattern, frequency, and severity of symptoms as
      well as the patient's age. Nasal congestion is typically the most bothersome
      symptom, although rhinorrhea, postnasal drip, and ocular symptoms are also
      problematic. Together, these symptoms may adversely impact the quality of life,
      work productivity, sleep quality, and the ability to perform daily activities,
      particularly when uncontrolled. Practice guidelines recognize that INCSs are the
      most effective medications for controlling allergic rhinitis symptoms, including
      nasal congestion. Available INCS products have comparable safety and efficacy
      profiles, but they differ in formulation characteristics and sensory attributes.
      Several barriers can impede the use of INCSs, including concerns about safety,
      misperceptions regarding the loss of response from frequent use, and undesirable
      sensations associated with intranasal administration. Given the increasing number
      of INCSs available OTC, pharmacists can help allay these concerns by discussing
      treatment expectations, recommending INCS products with favorable formulation
      characteristics, and reviewing proper use and technique for the administration of
      the selected product. These steps can help to foster a collaborative relationship
      between the patient and the pharmacist in the treatment of allergic rhinitis.

PMID- 29354558
TI  - Defining pharmacy and its practice: a conceptual model for an international
      audience.
AB  - Background: There is much fragmentation and little consensus in the use of
      descriptors for the different disciplines that make up the pharmacy sector.
      Globalization, reprofessionalization and the influx of other disciplines means
      there is a requirement for a greater degree of standardization. This has not been
      well addressed in the pharmacy practice research and education literature.
      Objectives: To identify and define the various subdisciplines of the pharmacy
      sector and integrate them into an internationally relevant conceptual model based
      on narrative synthesis of the literature. Methods: A literature review was
      undertaken to understand the fragmentation in dialogue surrounding definitions
      relating to concepts and practices in the context of the pharmacy sector. From a
      synthesis of this literature, the need for this model was justified. Key
      assumptions of the model were identified, and an organic process of development
      took place with the three authors engaging in a process of sense-making to
      theorize the model. Results: The model is "fit for purpose" across multiple
      countries and includes two components making up the umbrella term "pharmaceutical
      practice". The first component is the four conceptual dimensions, which outline
      the disciplines including social and administrative sciences, community pharmacy,
      clinical pharmacy and pharmaceutical sciences. The second component of the model
      describes the "acts of practice": teaching, research and professional advocacy;
      service and academic enterprise. Conclusions: This model aims to expose issues
      relating to defining pharmacy and its practice and to create dialogue. No model
      is perfect, but there are implications for what is posited in the areas of
      policy, education and practice and future research. The main point is the need
      for increased clarity, or at least beginning the discussion to increase the
      clarity of definition and consistency of meaning in-and-across the pharmacy
      sector locally, nationally and internationally.

PMID- 29354559
TI  - Addressing varenicline adherence through repackaging in a dose administration
      aid.
AB  - Background: Ensuring adherence to prescribed smoking cessation medications, such
      as Champix(r) (varenicline), is essential during a quit attempt as non-adherence
      can significantly reduce the likelihood of achieving prolonged smoking
      abstinence. The use of dose administration aids may improve adherence, though
      medication stability on repackaging is not guaranteed, due to a lack of available
      data from manufacturers supporting this practice. Objective: To determine the
      suitability for repackaging varenicline tartrate tablets into a dose
      administration aid, by assessing its physical and chemical stability after being
      repackaged and stored at ambient conditions for 6 weeks. Methods: Varenicline
      tartrate (1.0 mg) tablets were repackaged into commercially available Webster
      pak(r) blister compartments and stored for 42 days at ambient conditions
      characteristic of a Zone IVB climate (30 +/- 2 degrees C and 75 +/- 5% relative
      humidity) according to the World Health Organization (WHO) guidelines on
      pharmaceutical stability testing. Physical and chemical tests were performed on
      the repackaged and control tablets, including an assessment of: tablet thickness,
      hardness, weight uniformity, friability, dissolution, disintegration, and content
      uniformity after exposure to ambient conditions and light according to
      International Council on Harmonisation of Technical Requirements of
      Pharmaceuticals for Human Use guideline Q1B. Results: Weight, friability, and
      thickness of the tablets complied with compendial standards. A validated high
      performance liquid chromatography method was used to confirm that after exposure
      to light, and repackaging at 30 degrees C/75% relative humidity, the tablets
      remained within the required 95%-105% of the stated drug content. However, tablet
      hardness and disintegration decreased over time, with tablets becoming softer and
      undergoing more rapid disintegration in water. Conclusion: Repackaging 1.0 mg
      varenicline tartrate tablets into a dose administration aid can be undertaken to
      improve adherence rates and therefore smoking abstinence rates. This can be
      performed without compromising either the physical or chemical stability of the
      tablets.

PMID- 29354560
TI  - The role of community pharmacists in patient counseling and health education: a
      survey of their knowledge and level of involvement in relation to type 2 diabetes
      mellitus.
AB  - Purpose: The present study aimed at evaluating the knowledge and level of
      involvement of community pharmacists in the provision of patient counseling and
      health education services for patients with DM and perceived barriers that limit
      the delivery of such services. Materials and methods: A self-administered
      questionnaire based-survey was undertaken from January to March, 2017 with 412
      pharmacists working in community pharmacies in six cities of Amhara regional
      state of Ethiopia: Debre Markos, Gondar, Dessie, Bahir Dar, Woldya, and Debre
      Birhan. Descriptive statistics, ANOVA, and Student's t-test were employed to
      examine different variables. Results: Community pharmacists were found to have
      poor knowledge and low level of involvement, with an overall mean score of 11.54
      and 2.06, respectively. A significant number of community pharmacists never
      practiced promoting smoking cessation (45.2%), counseling on good foot care
      techniques (33.7%), and counseling on the potential impact of over-the-counter
      and herbal drugs on DM management (34%). On the other hand, describing the right
      time to administer antidiabetic medications (46%) and counseling on suitable
      administration, handling, and storage of insulin (33.7%) were done more
      frequently. The main reported barriers to the delivery of these services were
      lack of knowledge or clinical skills, lack of access to additional training
      programs, and lack of personnel or resources. Conclusion: The present study
      revealed a poor knowledge and low level of involvement in counseling and health
      education services for patients with DM. Lack of knowledge or clinical skills was
      the most commonly reported barrier for providing such services. In order to
      better integrate community pharmacies into future public health programs and
      optimize the contribution of pharmacists, interventions should focus on
      overcoming the identified barriers.

PMID- 29354561
TI  - Does an integrated information technology system provide support for community
      pharmacists undertaking Discharge Medicines Reviews? An exploratory study.
AB  - Objective: The aim of this study was to explore the views of community
      pharmacists participating in the pilot of a secure online platform in Wales, the
      Choose Pharmacy application (CPA), with particular interest in the electronic
      Discharge Advice Letters (e-DALs) and online Discharge Medicines Review (DMR)
      form. Materials and methods: A qualitative approach with semi-structured
      interviews was adopted. A gatekeeper from National Health Service Wales
      Informatics Service identified 35 pharmacies, of the 43 pharmacies where the CPA
      had been implemented, that had completed at least one DMR, and these were
      therefore invited to an interview. Results: A total of 17 pharmacists were
      interviewed. Overall, the results were positive and CPA and e-DAL were perceived
      to facilitate continuity of care between care settings. The design and usability
      were perceived as good as pharmacists could navigate the CPA without problems;
      many felt this was due to the level of training they had received. Many
      pharmacists were happy for other services to be included on the platform due to
      its ease of use and automatic reimbursement. Several pharmacists felt that
      communication between primary and secondary care can be further improved as the
      uptake of e-DAL increases. Conclusion: CPA was found to streamline the completion
      of online DMR improving continuity of care between primary and secondary sectors,
      which in turn should improve patient safety on discharge from hospital.

PMID- 29354562
TI  - Opinion of hospital pharmacy practitioners toward the Continuing Pharmacy
      Education program: a study from a tertiary care hospital in central Nepal.
AB  - Background: Meeting participants' needs and matching their preferences are
      important prerequisites for an effective Continuing Pharmacy Education (CPE)
      program. The objective of this pilot study was to assess the opinion of hospital
      pharmacy practitioners with respect to the CPE program. Methods: The pretested
      questionnaires were distributed to 20 pharmacy practitioners working in a
      pharmacy at a tertiary care hospital in Nepal which asked for their opinions and
      suggestions with respect to the CPE program. Descriptive statistics were
      performed using IBM SPSS version 20. Results: Topics related to skills
      development (75%) and recent innovations in pharmacy practice (65%) were mostly
      preferred. Live (in-person) presentations (80%) and small group discussion (60%)
      were the most suitable methods for delivery. Improving knowledge (75%), improving
      skills (60%) and keeping up-to-date in the latest information (60%) were major
      motivating factors to participate, while lack of time (75%) was a major barrier.
      Approximately 55% of the participants believed that face-to-face interview was a
      suitable method for evaluating the effectiveness. Allocation of separate time for
      the program, assessing baseline knowledge and skills of the participants along
      with delivery of quality materials in an understandable way were the top common
      suggestions for improving the CPE program. Conclusion: Hospital pharmacy
      practitioners' opinions and suggestions were assessed with respect to the CPE
      program and this was upgraded accordingly to meet their expectations.

PMID- 29354564
TI  - Displaying medication costs on dispensing labels as a strategy to reduce wastage:
      views of the Welsh general public.
AB  - Introduction: In 2015, the UK health secretary made public an intention to
      include the value of medicines costing over L20 on dispensing labels as an
      attempt to reduce wastage attributable to patient behavior. However, there is a
      lack of evidence investigating the potential effect or feasibility of this
      proposal, and concerns have been raised that it may introduce new problems in
      vulnerable groups. This pilot study aimed to gather views of the Welsh general
      public on this subject. Methods: Six focus groups from within key population
      groups were conducted. A snowball sampling strategy was employed with
      participants recruited via a neutral gatekeeper. Focus groups session were audio
      recorded and transcribed verbatim and iterative thematic analysis was used to
      identify emergent themes. Results: Six focus groups were conducted. Three key
      themes were identified: "influence of cost" - whereby participants expressed
      concern about cost linking to their perceived value, guilt for needing prescribed
      medication and irrelevance of cost if the medication was considered necessary;
      "knowledge is power" - whereby participants expressed a desire to know more about
      their medicines and engage with health care professionals about them, and felt
      information on dispensing labels alone would be insufficient to support this and
      "blame the system" - whereby participants felt responsibility for wastage should
      be shared by both system and patient and identified existing wasteful practices
      such as inappropriate prescribing, ordering and disposal of returned medicines.
      Conclusion: Findings were largely consistent with criticisms publicized by
      professional bodies that introducing cost may serve to make patients feel guilty
      or unworthy rather than encourage them to use their medicines appropriately.
      Similarly, providing cost information on labels alone was considered insufficient
      and therefore additional counseling or education would be necessary to prevent
      misunderstanding. The acknowledgment of system factors contributing to wastage
      highlights an important role for pharmacists to become involved in using
      medicines more cost-effectively. However, cost was considered irrelevant if the
      medicine was deemed necessary by the patient, and therefore more mindful
      prescribing of superfluous items should be promoted.

PMID- 29354563
TI  - Methylphenidate extended-release oral suspension for the treatment of attention
      deficit/hyperactivity disorder: a practical guide for pharmacists.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition
      that affects children, adolescents, and adults worldwide. The purpose of this
      review was to inform pharmacists of the numerous options to treat ADHD, with a
      focus on one of the more recently approved formulations, methylphenidate extended
      release oral suspension (MEROS). Symptoms of ADHD can negatively impact an
      individual's health and quality of life and impair function in multiple settings.
      Psychostimulants such as methylphenidate- and amphetamine-based agents are first
      line pharmacologic treatments for ADHD. However, there are multiple formulations,
      including immediate release (administered two to three times/day), solid extended
      release (ER), or transdermal patch. MEROS is a once daily, long-acting liquid
      preparation that has demonstrated favorable safety and efficacy in patients with
      ADHD. MEROS may improve treatment adherence in patients who cannot tolerate or
      have difficulties administering pill or transdermal patch formulations.

PMID- 29354565
TI  - Identification of the benefits, enablers and barriers to integrating junior
      pharmacists into the ward team within one UK-based hospital.
AB  - Introduction: A high nurse-vacancy rate combined with high numbers of
      applications for junior pharmacist roles resulted in Colchester Hospital
      University National Health System Foundation Trust trial employing junior
      pharmacists into traditional nursing posts with the aim of integrating
      pharmacists into the ward team and enhancing local medicines optimization. The
      aim of the evaluation was to describe the implementation process and practice of
      the integrated care pharmacists (ICPs) in order to inform future innovations of a
      similar nature. Methods: Four band 6 ward-based ICPs were employed on two wards
      funded within current ward staffing expenditure. With ethical committee approval,
      interviews were undertaken with the ICPs and focus groups with ward nurses,
      senior ward nurses and members of the medical team. Data were analyzed
      thematically to identify service benefits, barriers and enablers. Routine ward
      performance data were obtained from the two ICP wards and two wards selected as
      comparators. Appropriate statistical tests were performed to identify differences
      in performance. Results: Four ICPs were interviewed, and focus groups were
      undertaken with three junior nurses, four senior nurses and three medical
      practitioners. Service enablers were continuous ward time, undertaking drug
      administration, positive feedback and use of effective communication methods.
      Barriers were planning, funding model, career development, and interprofessional
      working and social isolation. ICPs were believed to save nurse time and improve
      medicines safety. The proportion of patients receiving medicine reconciliation
      within 24 hours increased significantly in the ICP wards. All ICPs had resigned
      from their role within 12 months. Discussion: It was believed that by locating
      pharmacists on the ward full time and allowing them to undertake medicines
      administration and medicines reconciliation, the nursing time would be saved and
      medicines safety improved. There was however significant learning to be derived
      from the implementation process, which may enable similar future models to be
      introduced more successfully.

PMID- 29354566
TI  - Neural Correlates of Motor Recovery Measured by SPECT at Six Months After Basal
      Ganglia Stroke.
AB  - Objective: To investigate neural correlates associated with recovery of motor
      function over 6 months in patients with basal ganglia (BG) stroke using
      acetazolamide (ACZ) stress brain-perfusion single-photon emission computed
      tomography (SPECT). Methods: Medical records of 22 patients presenting first-ever
      BG stroke were retrospectively reviewed. Regional cerebral blood flow (CBF) and
      cerebrovascular reserve (CVR) were measured for 9 regions in each cerebral
      hemisphere (primary motor cortex, supplementary motor area, premotor cortex,
      prefrontal cortex, temporal lobe, parietal lobe, occipital lobe, BG, and
      thalamus). The Fugl-Meyer Assessment (FMA) motor score was used to assess motor
      function. Results: After ACZ injection, CBF of all regions of interest (ROIs)
      increased compared with baseline. Baseline CBF of all ROIs was not significantly
      correlated with changes in FMA upper or lower motor score. However, multivariate
      analysis revealed CVR was significantly associated with change in FMA upper score
      in the ipsilateral primary motor cortex (R2=0.216, p=0.017), the ipsilateral
      parietal lobe (R2=0.135, p=0.029), and the contralateral primary motor cortex
      (R2=0.210, p=0.041). Conclusion: CVR in the bilateral primary motor cortex and
      ipsilateral parietal lobe was associated with restoration of upper motor function
      6 months after BG stroke. SPECT is a readily available imaging modality useful in
      studying brain residual function in patients with BG stroke.

PMID- 29354567
TI  - The Correlation Between Clinical Characteristics and Radionuclide Salivagram
      Findings in Patients With Brain Lesions: A Preliminary Study.
AB  - Objective: To evaluate the correlation between radionuclide salivagram findings
      and clinical characteristics in dysphagic patients with brain lesions. Methods:
      The medical records of 35 dysphagic patients with brain lesions who
      simultaneously underwent both a videofluoroscopic swallowing study (VFSS) and
      radionuclide salivagram were analyzed retrospectively. The subjects were divided
      into two groups according to the presence of aspiration on a salivagram (group A,
      patients with aspiration on the salivagram; group B, patients with no aspiration
      on the salivagram). The differences between clinical characteristics and VFSS
      findings (penetration-aspiration scale [PAS]) between the two groups were
      analyzed. Results: Eleven out of 35 patients displayed salivary aspiration on the
      radionuclide salivagram. There were no significant differences between the two
      groups according to age, sex, disease duration, PAS on VFSS and feeding methods
      (p>=0.05). The incidence of aspiration pneumonia was significantly higher in
      group A. In a multivariate logistic regression analysis with forward stepwise
      method, the Mini-Mental State Examination (MMSE) score was the only significant
      parameter in predicting positive findings in salivagrams (odds ratio=0.760; 95%
      confidence interval [CI], 0.625-0.923; p=0.006). The area under the receiver
      operating characteristic curve (AUC) of the MMSE score for positive detection in
      salivagrams was 0.855 (95% CI, 0.689-0.953; p<0.0001). The optimal cut-off value
      was 7 for the MMSE score (sensitivity 72.73%, specificity 100%). Conclusion: In
      patients with brain lesions who complain of dysphagia, the MMSE score was
      correlated with salivary aspiration. If patients present with a score of 7 or
      less on the MMSE, performing a radionuclide salivagram may helpful for early
      detection of patients at high risk of aspiration pneumonia induced from salivary
      aspiration.

PMID- 29354568
TI  - Anatomical Correlates of Neuropsychological Deficits Among Patients With the
      Cerebellar Stroke.
AB  - Objective: To investigate the anatomical correlates of the neuropsychological
      deficits in patients with the cerebellar stroke. Methods: We screened patients
      who were admitted to the National Rehabilitation Center with the cerebellar
      stroke between October 2012 and November 2016. The patients with the cerebellar
      stroke who underwent neuropsychological testing for which the Seoul
      Neuropsychological Screening Battery (SNSB) or the SNSB-II were enrolled. The
      neuropsychological function capacities were compared in accordance with the
      stroke type (hemorrhagic vs. ischemic) and the location (right/left anterior,
      right/left posterior intermediate, right/left posterior lateral lobe, and
      vermis). Mean z-scores were computed to compare the patient performances with the
      population averages. Results: Twenty-six patients (15 with ischemic stroke and 11
      with hemorrhagic stroke) with a mean age of 54.8+/-16.6 years were assessed 8.8+/
      9.2 months after the stroke. Differences in the neuropsychological functioning
      according to the stroke type were not observed. All of the numerical subtests of
      the stroke patients showed significantly poorer performances compared with the
      population averages (mean z-score <0), and some of the subtests revealed abnormal
      performances in attention-, visuospatial function-, memory-, and
      frontal/executive function-related tasks (mean z-score <-1). The patients with
      the presence of a lesion in the right posterior intermediate lobe of the
      cerebellum showed a poorer performance in the subtests evaluating the executive
      function including the Korean-version Stroop Test (p=0.04), the Digit Symbol
      Coding Test (p=0.01), and the Korean-version Trail Making Test (p=0.02) compared
      with the patients without that lesion. Conclusion: The present study confirms
      that the cerebellar stroke affects the neuropsychological functioning which is
      associated with the anatomical site of stroke.

PMID- 29354569
TI  - Effects of Overactive Bladder Symptoms in Stroke Patients' Health Related Quality
      of Life and Their Performance Scale.
AB  - Objective: To identify the effects of overactive bladder (OAB) symptoms on the
      health-related quality of life (HRQOL) in stroke patients since OAB symptoms are
      common in such patients, but their effects on stroke rehabilitation over time are
      unclear. Methods: This study included 30 post-acute stroke patients who had been
      admitted for rehabilitation treatments. All participants completed a
      questionnaire evaluating urinary symptoms, including the Overactive Bladder
      Symptom Score (OABSS) and general HRQOL with a Short-Form 36 (SF-36) health
      survey. We assessed their performance in terms of the Function Ambulation
      Category, Modified Rankin Scale (MRS), Modified Barthel Index, and Mini-Mental
      State Examination (MMSE). All assessments were carried out twice at baseline and
      at 3 months. We divided patients into an OAB and non-OAB group with OABSS. A
      correlation analysis and multivariate regression were then performed. Results:
      All performance scales showed an improvement over 3 months in the non-OAB group
      (n=18; p<0.02), but, MRS and MMSE scores did not improve significantly in the OAB
      group (n=12) (p=0.15 and p=0.20, respectively). In the OAB group, the vitality
      and mental health scores significantly decreased over 3 months (p=0.011 and
      p=0,041, respectively), and the mental component summary (MCS) score showed a
      marginal decrease over 3 months (p=0.05). A multivariate regression analysis
      revealed that OAB symptoms were negatively correlated with the 3 months MCS score
      (B=-8.15, p=0.034). Conclusion: These results indicated that OAB symptoms could
      have negative effects on HRQOL and performance in patients suffering from a
      stroke.

PMID- 29354570
TI  - Decrement of Serum Vitamin D Level After Stroke.
AB  - Objective: To investigate the serum vitamin D level and its determinant factors
      in stroke patients. Methods: Fifty-one stroke patients who had documented serum
      level of 25-hydroxyvitamin D(25(OH)D) were included. Patients were divided into
      subacute (n=23) and chronic groups (n=28). The mean levels of 25(OH)D of the two
      groups were compared. Correlations between each 25(OH)D level and post-stroke
      duration were also analyzed. To assess other possible influencing factors,
      patients were subdivided by ambulation ability and feeding methods for comparison
      of 25(OH)D level. Results: The mean level of 25(OH)D was significantly lower in
      the chronic group than in the subacute group (12.3 vs. 16.3 ng/mL; p<0.05). The
      serum 25(OH)D level decreased according to the duration after stroke (r=-0.52,
      p=0.01). Patients with a history of total parenteral nutrition had lower 25(OH)D
      levels than subjects who had enteral nutrition in the subacute group (7.3 vs.
      18.8 ng/mL; p<0.01). However, the levels of 25(OH)D were not different between
      the oral feeding and tube feeding groups. Among the chronic group subjects,
      patients who could walk without assistance had higher 25(OH)D levels than non
      ambulatory patients (ambulatory vs. non-ambulatory group; 18.3 vs. 11.3 ng/mL;
      p<0.05). Conclusion: After stroke onset, serum vitamin D level decreases with
      time regardless of feeding methods, and total parenteral nutrition may aggravate
      its deficiency. In terms of long-term care, non-ambulatory patients might be at a
      higher risk of vitamin D deficiency. Supplementation of vitamin D should be
      considered especially for stroke patients who are non-ambulatory and on total
      parenteral nutrition.

PMID- 29354571
TI  - Heart Rate Variability Among Children With Acquired Brain Injury.
AB  - Objective: To find evidence of autonomic imbalance and present the heart rate
      variability (HRV) parameters that reflect the severity of paroxysmal sympathetic
      hyperactivity (PSH) in children with acquired brain injury (ABI). Methods:
      Thirteen children with ABI were enrolled and age- and sex-matched children with
      cerebral palsy were selected as the control group (n=13). The following HRV
      parameters were calculated: time-domain indices including the mean heart rate,
      standard deviation of all average R-R intervals (SDNN), root mean square of the
      successive differences (RMSSD), physical stress index (PSI), approximate entropy
      (ApEn); successive R-R interval difference (SRD), and frequency domain indices
      including total power (TP), high frequency (HF), low frequency (LF), normalized
      HF, normalized LF, and LF/HF ratio. Results: There were significant differences
      between the ABI and control groups in the mean heart rate, RMSSD, PSI and all
      indices of the frequency domain analysis. The mean heart rate, PSI, normalized
      LF, and LF/HF ratio increased in the ABI group. The presence of PSH symptoms in
      the ABI group demonstrated a statistically significant decline of the SDNN, TP,
      ln TP. Conclusion: The differences in the HRV parameters and presence of PSH
      symptoms are noted among ABI children compared to an age- and sex-matched control
      group with cerebral palsy. Within the ABI group, the presence of PSH symptoms
      influenced the parameters of HRV such as SDNN, TP and ln TP.

PMID- 29354572
TI  - Association of Post-extubation Dysphagia With Tongue Weakness and Somatosensory
      Disturbance in Non-neurologic Critically Ill Patients.
AB  - Objective: To prospectively assess the association between impoverished
      sensorimotor integration of the tongue and lips and post-extubation dysphagia
      (PED). Methods: This cross-sectional study included non-neurologic critically ill
      adult patients who required endotracheal intubation and underwent
      videofluoroscopic swallowing study (VFSS) between October and December 2016.
      Participants underwent evaluation for tongue and lip performance, and oral
      somatosensory function. Demographic and clinical data were retrieved from medical
      records. Results: Nineteen patients without a definite cause of dysphagia were
      divided into the non-dysphagia (n=6) and the PED (n=13) groups based on VFSS
      findings. Patients with PED exhibited greater mean duration of intubation
      (11.85+/-3.72 days) and length of stay in the intensive care unit (LOS-ICU;
      13.69+/-3.40 days) than those without PED (6.83+/-5.12 days and 9.50+/-5.96 days;
      p=0.02 and p=0.04, respectively). The PED group exhibited greater incidence of
      pneumonia, higher videofluoroscopy swallow study dysphagia scale score, higher
      oral transit time, and lower tongue power and endurance and lip strength than the
      non-dysphagia groups. The differences in two-point discrimination and sensations
      of light touch and taste among the two groups were insignificant. Patients
      intubated for more than 7 days exhibited lower maximal tongue power and tongue
      endurance than those intubated for less than a week. Conclusion: Duration of
      endotracheal intubation, LOS-ICU, and oromotor degradation were associated with
      PED development. Oromotor degradation was associated with the severity of
      dysphagia. Bedside oral performance evaluation might help identify patients who
      might experience post-extubation swallowing difficulty.

PMID- 29354573
TI  - Degree of Contribution of Motor and Sensory Scores to Predict Gait Ability in
      Patients With Incomplete Spinal Cord Injury.
AB  - Objective: To identify different contributions of motor and sensory variables for
      independent ambulation of patients with incomplete spinal cord injury (SCI), and
      reveal the most significant contributors among the variables. Methods: The
      retrospective study included 30 patients with incomplete SCI and lesions were
      confirmed by magnetic resonance imaging. Motor and sensory scores were collected
      according to the International Standards for Neurological Classification of
      Spinal Cord Injury. The variables were analyzed by plotting ROC (receiver
      operating characteristic) curves to estimate their differential contributions for
      independent walking. The most significant functional determinant was identified
      through the subsequent logistic regression analysis. Results: Motor and sensory
      scores were significantly different between the ambulators and non-ambulators.
      The majority was associated to the function of lower extremities. Calculation of
      area under ROC curves (AUC) revealed that strength of hip flexor (L2) (AUC=0.905,
      p<0.001) and knee extensor (L3) (AUC=0.820, p=0.006) contributed the greatest to
      independent walking. Also, hip flexor strength (L2) was the single most powerful
      predictor of ambulation by the logistic regression analysis (odds ratio=6.3,
      p=0.049), and the model fit well to the data. Conclusion: The most important
      potential contributor for independent walking in patients with incomplete SCI is
      the muscle strength of hip flexors, followed by knee extensors compared with
      other sensory and motor variables.

PMID- 29354574
TI  - Biomechanical Parameters in Plantar Fasciitis Measured by Gait Analysis System
      With Pressure Sensor.
AB  - Objective: To investigate the differences in biomechanical parameters measured by
      gait analysis systems between healthy subjects and subjects with plantar
      fasciitis (PF), and to compare biomechanical parameters between 'normal,
      barefooted' gait and arch building gait in the participants. Methods: The
      researchers evaluated 15 subjects (30 feet) with bilateral foot pain and 15
      subjects (15 feet) with unilateral foot pain who had a clinical diagnosis of PF.
      Additionally, 17 subjects (34 feet) who had no heel pain were recruited. Subjects
      were excluded if they had a traumatic event, prior surgery or fractures of the
      lower limbs, a leg length discrepancy of 1 cm or greater, a body mass index
      greater than 35 kg/m2, or had musculoskeletal disorders. The participants were
      asked to walk with an arch building gait on a treadmill at 2.3 km/hr for 5
      minutes. Various gait parameters were measured. Results: With the arch building
      gait, the PF group proved that gait line length and single support line were
      significantly decreased, and lateral symmetry of the PF group was increased
      compared to that of the control group. The subjects with bilateral PF displayed
      significantly increased maximum pressure over the heel and the forefoot during
      arch building gait. In addition, the subjects with unilateral PF showed
      significantly increased maximum pressure over the forefoot with arch building
      gait. Conclusion: The researchers show that various biomechanical differences
      exist between healthy subjects and those with PF. Employing an arch building gait
      in patients with PF could be helpful in changing gait patterns to normal
      biomechanics.

PMID- 29354575
TI  - Muscle Mass, Strength, Mobility, Quality of Life, and Disease Severity in
      Ankylosing Spondylitis Patients: A Preliminary Study.
AB  - Objective: To determine if there is muscle mass reduction in patients with
      ankylosing spondylitis (AS) compared to the general population and to examine the
      relationship between skeletal muscle mass, quality of life (QOL), strength, and
      mobility in patients with AS. Methods: A total of 30 AS patients were enrolled in
      this study. Skeletal muscle mass was measured by bioelectrical impedance
      analysis, and it was expressed as the skeletal muscle mass index (SMI). QOL was
      assessed using the EuroQOL (EQ-5D). To measure mobility, the modified Schober
      test and chest expansion test were used. To measure grip strength as a measure of
      muscle strength, we used the hydraulic hand dynamometer. Additionally, we divided
      the patients into two groups according to the degree of X-ray finding and
      compared the differences between the two groups. Results: There was no
      significant reduction in skeletal muscle mass in patients with AS compared to the
      general population. Also, there was no significant correlation between SMI and
      QOL. On the other hand, there was a significant positive correlation between SMI
      and mobility, and grip strength. A significant positive correlation was found
      between mobility and QOL. Additionally, there was a statistically significant
      difference in mobility between the two groups according to the degree of X-ray
      finding. Conclusion: Maintaining muscle mass in AS patients may not be helpful
      for improving QOL, but it may contribute to achieving adequate mobility and
      strength.

PMID- 29354576
TI  - Long-Term Efficacy of Rehabilitation Following Arthroscopic Synovectomy in
      Patients With Rheumatoid Arthritis Treated With Biologic Agents.
AB  - Objective: To investigate the long-term efficacy of rehabilitation following
      arthroscopic synovectomy in patients with rheumatoid arthritis treated with
      biologic agents. Methods: Arthroscopic synovectomy was performed in 29 joints of
      17 patients, which were divided into two groups. Group 1 included arthroscopic
      synovectomy plus rehabilitation for 19 joints in 10 patients, and group 2
      included arthroscopic synovectomy without rehabilitation for 10 joints in 7
      patients. The Disease Activity Score C-reactive protein (DAS28-CRP), Health
      Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Independence
      Measure (FIM) values (motor subscale) at 9.7 years after arthroscopic synovectomy
      were evaluated to identify the clinical factors related to outcomes. Results: The
      increase in FIM score was significant in group 1 (p=0.05). HAQ-DI at 9 years was
      significantly decreased in group 1 (p=0.02). Therefore, arthroscopic synovectomy
      with rehabilitation was significant in improving FIM and HAQ-DI scores over a
      long period. Multiple regression analysis of FIM scores at 9 years indicated that
      rehabilitation (p=0.03) and disease duration (p=0.02) were significantly related
      to outcomes. FIM score at 9 years was significantly negatively correlated with
      disease duration (p=0.01, r=-0.58, Y=88.89-0.21X). Conclusion: Rehabilitation
      following arthroscopic synovectomy was effective in achieving high FIM scores
      over time in patients with rheumatoid arthritis.

PMID- 29354577
TI  - Effects of Nutritional Status on 6-Month Outcome of Hip Fractures in Elderly
      Patients.
AB  - Objective: To identify the prevalence of malnutrition in elderly hip fracture and
      to investigate the relationship between hip fracture patients and malnutrition on
      functional recovery and mortality. Methods: All hip fracture patients age >65
      years admitted to a rehabilitation unit were recruited from July 2015 to June
      2016. Nutritional status was assessed by Mini-Nutritional Assessment Short-Form
      (MNA-SF) within 72 hours of admission. Patients were reassessed at 6 months for
      functional status and place of residence. Length of hospital stay, in-patient
      mortality rate, and 6-month mortality rate were also recorded. Results: There
      were 218 patients recruited. The mean age was 83.5+/-7.5 years. According the MNA
      SF, 46 (21.1%) were well nourished, 115 (52.6%) were at risk of malnutrition, and
      57 (26.1%) were malnourished. Malnourished individuals were significantly older,
      had lower Mini-Mental State Examination score and albumin level, were
      functionally more dependent and were more likely to reside in elderly care
      facility. A higher proportion of elderly care residents were at-risk or were
      malnourished on admission, discharge and at 6 months. Functional recovery was
      slower in the malnourished group. In-patient mortality was higher in malnourished
      individuals compared to those at risk of malnourishment and well-nourished
      individuals. Conclusion: The prevalence of malnutrition is high and is associated
      with poor functional recovery and elderly care placement. Residents of elderly
      care facilities are especially at risk due a higher prevalence of malnourishment.
      Health authorities are encouraged to evaluate the dietetic component in elderly
      care facilities and initiate nutrition supplementation in their planning of
      healthcare resources.

PMID- 29354578
TI  - Relationships Between Self-awareness and Clinical Diagnostic Findings of Abnormal
      Foot Arch Height in Koreans.
AB  - Objective: To see how people think about their own feet, and evaluate whether
      there are correlations among self-awareness of the participants and clinical
      examination findings. Methods: Adult twins and their families who participated in
      the Healthy Twin study from May 2008 to April 2010 were recruited. Participants
      were asked whether they thought their feet were normal, flat, or cavus. The
      lateral talometatarsal angles were measured on foot X-rays to determine the foot
      arch height. Using the podoscopic footprints taken with the podobaroscope, the
      Staheli arch index was also measured. Kappa statistics were used to calculate
      degree of agreement among the three measurement methods. Results: Self-awareness
      and radiographic findings were significantly different (Pearson chi-square test,
      p=0.000) and only slightly agreed (kappa measure of agreement=0.136, p=0.000).
      Self-awareness and podoscopy results revealed a significant difference (Pearson
      chi-square test, p=0.000), with only slight agreement (kappa measure of
      agreement=0.072, p=0.000). Conclusion: There is significant disagreement between
      patients' perception of their feet and actual test results. Many people may have
      an incorrect assumption about their own foot conditions that may be reflected in
      improper management. Dissemination of accurate information about foot disorders
      by foot clinicians would be helpful.

PMID- 29354579
TI  - Comparison of Clinical Characteristics Between Patients With Different Causes of
      Vocal Cord Immobility.
AB  - Objective: To analyze the clinical characteristics between neurogenic and non
      neurogenic cause of vocal cord immobility (VCI). Methods: The researchers
      retrospectively reviewed clinical data of patients who underwent laryngeal
      electromyography (LEMG). LEMG was performed in the bilateral cricothyroid and
      thyroarytenoid muscles. A total of 137 patients were enrolled from 2011 to 2016,
      and they were assigned to either the neurogenic or non-neurogenic VCI group,
      according to the LEMG results. The clinical characteristics were compared between
      the two groups and a subgroup analysis was done in the neurogenic group. Results:
      Among the 137 subjects, 94 patients had nerve injury. There were no differences
      between the neurogenic and non-neurogenic group in terms of demographic data,
      underlying disease except cancer, and premorbid events. In general
      characteristics, cancer was significantly higher in the neurogenic group than non
      neurogenic group (p=0.001). In the clinical findings, the impaired high pitched
      'e' sound and aspiration symptoms were significantly higher in neurogenic group
      (p=0.039 for impaired high pitched 'e' sound; p=0.021 for aspiration symptoms),
      and sore throat was more common in the non-neurogenic group (p=0.014). In the
      subgroup analysis of neurogenic group, hoarseness was more common in recurrent
      laryngeal neuropathy group than superior laryngeal neuropathy group (p=0.018).
      Conclusion: In patients with suspected vocal cord palsy, impaired high pitched
      'e' sound and aspiration symptoms were more common in group with neurogenic cause
      of VCI. Hoarseness was more frequent in subjects with recurrent laryngeal
      neuropathy. Thorough clinical evaluation and LEMG are important to differentiate
      underlying cause of VCI.

PMID- 29354580
TI  - Rapid, Objective and Non-invasive Diagnosis of Sudomotor Dysfunction in Patients
      With Lower Extremity Dysesthesia: A Cross-Sectional Study.
AB  - Objective: To determine whether patients with lumbosacral (LS) radiculopathy and
      peripheral polyneuropathy (PPNP) exhibit sudomotor abnormalities and whether
      SUDOSCAN (Impeto Medical, Paris, France) can complement nerve conduction study
      (NCS) and electromyography (EMG). Methods: Outpatients with lower extremity
      dysesthesia underwent electrophysiologic studies and SUDOSCAN. They were
      classified as normal (group A), LS radiculopathy (group B), or PPNP (group C).
      Pain severity was measured by the Michigan Neuropathy Screening Instrument (MNSI)
      and visual analogue scale (VAS). Demographic features, electrochemical skin
      conductance (ESC) values on hands and feet, and SUDOSCAN-risk scores were
      analyzed. Results: There were no statistical differences in MNSI and VAS among
      the three groups. Feet-ESC and hands-ESC values in group C were lower than group
      A and B. SUDOSCAN-risk score in group B and C was higher than group A. With a cut
      off at 48 microSiemens of feet-ESC, PPNP was detected with 57.1% sensitivity and
      94.2% specificity (area under the curve [AUC]=0.780; 95% confidence interval
      [CI], 0646-0.915). With a SUDOSCAN-risk score cut-off at 29%, NCS and EMG
      abnormalities related to LS radiculopathy and PPNP were detected with 64.1%
      sensitivity and 84.2% specificity (AUC=0.750; 95% CI, 0.674-0.886). Conclusion:
      SUDOSCAN can discriminate outpatients with abnormal electrophysiological findings
      and sudomotor dysfunction. This technology may be a complementary tool to NCS and
      EMG in outpatients with lower extremity dysesthesia.

PMID- 29354581
TI  - Relationship Between Post-exercise Heart Rate Recovery and Changing Ratio of
      Cardiopulmonary Exercise Capacity.
AB  - Objective: To determine whether heart rate recovery (HRR) following an exercise
      tolerance test (ETT) is correlated with a changing ratio of peak oxygen
      consumption (VO2) and maximal metabolic equivalents (METmax). Methods: A total of
      60 acute myocardial infarction (AMI) patients who underwent ETT at both
      assessment points - 3 weeks (T0) after the AMI attack and 3 months after T0 (T1)
      were included. After achieving a peak workload, the treadmill was stopped with a
      5-minute cooldown period, and the patients recovered in a comfortable and relaxed
      seated position. HRR was defined as the difference between the maximal heart rate
      (HRmax) and the HR measured at specific time intervals - immediately after the
      cool down period (HRR-0) and 3 minutes after the completion of the ETT (HRR-3).
      Results: HRR-0 and HRR-3 increased over time, whereas VO2max and METmax did not
      show significant changes. There was a positive correlation between HRR at T0 and
      the exercise capacity at T0. HRR at T0 also showed a positive correlation with
      the exercise capacity at T1. There was no significant correlation between HRR
      measured at T0 and the change in the ratio of VO2max and METmax, as calculated by
      subtracting VO2max and METmax obtained at T0 from those obtained at T1, divided
      by VO2max at T0 and multiplied by 100. Conclusion: Post-exercise HRR measured at
      3 weeks after the AMI onset can reflect the exercise capacity 3 months after the
      first ETT. However, it may be difficult to correlate post-exercise HRR at T0 with
      the degree of increase in cardiopulmonary exercise capacity in patients with AMI.

PMID- 29354582
TI  - The Differences in Cardiac Rehabilitation Outcomes by Age in Myocardial
      Infarction: A Preliminary Study.
AB  - Objective: To determine the age-related changes in cardiac rehabilitation (CR)
      outcomes, which includes hemodynamic and metabolic factors, in patients with
      myocardial infarction (MI). Methods: CR was administered for 8 weeks to 32 men
      (mean age, 54.0+/-8.8 years) who underwent percutaneous coronary intervention for
      acute MI between July 2012 and January 2016. The exercise tolerance tests were
      performed before and after the CR. The results were stratified based on a cut-off
      age of 55 years. Results: In the whole patient group, the hemodynamic variables
      such as the resting heart rate (HRrest), systolic blood pressure (SBPrest),
      submaximal HR (HRsubmax), SBP (SBPsubmax), and rate pressure product (RPPsubmax)
      significantly decreased and the maximal HR (HRmax) and RPP (RPPmax) significantly
      increased. All metabolic variables displayed significant improvement, to include
      maximal oxygen consumption (VO2max) and ventilation (VEmax), anaerobic threshold
      (AT), and the maximal oxygen pulse (O2pulsemax). However, upon stratification by
      age, those who were younger than 55 years of age exhibited significant changes
      only in the HRrest and RPPsubmax and those aged 55 years old or greater displayed
      significant changes in all hemodynamic variables except diastolic BP. Both groups
      displayed significant increases in the VO2max, VEmax, and AT; the older group
      also exhibited a significant increase in O2pulsemax. The magnitude of the changes
      in the hemodynamic and metabolic variables before and after CR, based on age, did
      not differ between the groups; although, it tended to be greater among the older
      participants of this study's sample. Conclusion: Because the older participants
      tended to show greater hemodynamic and metabolic changes due to CR, a more
      aggressive CR program must be administered to elderly patients with MI.

PMID- 29354583
TI  - Long-Term Outcome of Amyotrophic Lateral Sclerosis in Korean Subjects.
AB  - Objective: To report the latest long-term outcome of amyotrophic lateral
      sclerosis (ALS) and to analyze the predictors of prognosis. Methods: Subjects who
      were diagnosed with ALS between January 2005 and December 2009 at a single
      institute were followed up until death or up to December 2014. Data regarding
      age, sex, date of onset, date of diagnosis, presence of bulbar symptoms on onset,
      date of initiation of non-invasive ventilation (NIV), and the date of
      tracheostomy were collected. Survival was assessed using Kaplan-Meier curves and
      multivariate analyses of the risk of death were performed using the Cox
      proportional hazards model. Results: Among 212 suspicious subjects, definite ALS
      was diagnosed in 182 subjects. The survival rate at 3 and 5 years from onset was
      61.5% and 40.1%, respectively, and the survival rate at 3 and 5 years post
      diagnosis was 49.5% and 24.2%, respectively. Further, 134 patients (134/182,
      73.6%) were initiated on NIV, and among them, 90 patients (90/182, 49.5%)
      underwent tracheostomy. Male gender and onset age of >=65 years were independent
      predictors of adverse survival. Conclusion: The analysis of long term survival in
      ALS showed excellent outcomes considering the overall poor prognosis of this
      disease.

PMID- 29354584
TI  - Quantitative Lymphoscintigraphy to Predict the Possibility of Lymphedema
      Development After Breast Cancer Surgery: Retrospective Clinical Study.
AB  - Objective: To predict the probability of lymphedema development in breast cancer
      patients in the early post-operation stage, we investigated the ability of
      quantitative lymphoscintigraphic assessment. Methods: This retrospective study
      included 201 patients without lymphedema after unilateral breast cancer surgery.
      Lymphoscintigraphy was performed between 4 and 8 weeks after surgery to evaluate
      the lymphatic system in the early postoperative stage. Quantitative
      lymphoscintigraphy was performed using four methods: ratio of radiopharmaceutical
      clearance rate of the affected to normal hand; ratio of radioactivity of the
      affected to normal hand; ratio of radiopharmaceutical uptake rate of the affected
      to normal axilla (RUA); and ratio of radioactivity of the affected to normal
      axilla (RRA). During a 1-year follow-up, patients with a circumferential
      interlimb difference of 2 cm at any measurement location and a 200-mL interlimb
      volume difference were diagnosed with lymphedema. We investigated the difference
      in quantitative lymphoscintigraphic assessment between the non-lymphedema and
      lymphedema groups. Results: Quantitative lymphoscintigraphic assessment revealed
      that the RUA and RRA were significantly lower in the lymphedema group than in the
      non-lymphedema group. After adjusting the model for all significant variables
      (body mass index, N-stage, T-stage, type of surgery, and type of lymph node
      surgery), RRA was associated with lymphedema (odds ratio=0.14; 95% confidence
      interval, 0.04-0.46; p=0.001). Conclusion: In patients in the early postoperative
      stage after unilateral breast cancer surgery, quantitative lymphoscintigraphic
      assessment can be used to predict the probability of developing lymphedema.

PMID- 29354585
TI  - Neuroanatomical Mechanism of Cerebellar Mutism After Stroke.
AB  - Cerebellar mutism (CM) is a rare neurological condition characterized by lack of
      speech due to cerebellar lesions. CM is often reported in children. We describe a
      rare case of CM after spontaneous cerebellar hemorrhage. The patient showed
      mutism, irritability, decreased spontaneous movements and oropharyngeal apraxia.
      Diffusion tensor imaging revealed significant volume reduction of medial frontal
      projection fibers from the corpus callosum. In Tracts Constrained by UnderLying
      Anatomy (TRACULA) analysis, forceps major and minor and bilateral cingulum
      angular bundles were not visualized. Cerebello-frontal pathway reconstructed from
      the FMRIB Software Library showed continuity of fibers, with decreased number of
      fibers on qualitative analysis. These results suggest that cerebello-frontal
      disconnection may be a neuroanatomical mechanism of CM. Damage of brain network
      between occipital lobe, cingulate and cerebellum caused by hemorrhage may also
      have role in the mechanism of CM in our case.

PMID- 29354586
TI  - Bulbar Myasthenia Gravis Superimposed in a Medullary Infarction Diagnosed by a
      Fiberoptic Endoscopic Evaluation of Swallowing With Simultaneous Tensilon
      Application.
AB  - In the elderly, myasthenia gravis (MG) can present with bulbar symptoms, which
      can be clinically difficult to diagnose from other neurological comorbid
      conditions. We describe a case of a 75-year-old man who had been previously
      diagnosed with dysphagia associated with medullary infarction but exhibited
      aggravation of the dysphagia later on due to a superimposed development of bulbar
      MG. After recovering from his initial swallowing difficulties, the patient
      suddenly developed ptosis, drooling, and generalized weakness with aggravated
      dysphagia. Two follow-up brain magnetic resonance imaging (MRI) scans displayed
      no new brain lesions. Antibodies to acetylcholine receptor and muscle-specific
      kinase were negative. Subsequent electrodiagnosis with repetitive nerve
      stimulation tests revealed unremarkable findings. A diagnosis of bulbar MG could
      only be established after fiberoptic endoscopic evaluation of swallowing (FEES)
      with simultaneous Tensilon application. After application of intravenous
      pyridostigmine, significant improvement in dysphagia and ptosis were observed
      both clinically and according to the FEES.

PMID- 29354588
TI  - Disruption of the Corticoreticular Tract in Pediatric Patients With Trunk
      Instability: A Diffusion Tensor Tractography Study.
AB  - The authors report the diffusion tensor tractography (DTT) findings of three
      pediatric patients with gait dysfunction and corticoreticular tract (CRT)
      disruption. All three patients showed unilateral trunk instability, but they did
      not show any spasticity or weakness of the distal extremities. Clinical
      evaluation of trunk instability using a Trunk Control Measurement Scale (TCMS)
      revealed that the more affected side had a lower score than the contralateral
      side. DTT showed disrupted CRTs in hemispheres contralateral to the hemiparetic
      sides, which were associated with unilateral proximal instability, although
      conventional MRI showed no abnormal lesion explaining the hemiplegic symptom.
      Compared to the results in age-matched controls, these three patients had
      decreased values of fractional anisotropy (FA) and tract volumes (TV) of the
      affected CRTs, and these values were also decreased compared to those in the
      contralateral side. On the other hand, values of FA and TV of the corticospinal
      tracts on the ipsilateral and contralateral sides were only marginally different.
      In conclusion, diffusion tensor imaging can be helpful for investigating the
      state of the CRT in pediatric patients with trunk instability and gait
      dysfunction.

PMID- 29354587
TI  - Botulinum Toxin Type A Injection for Neuropathic Pain in a Patient With a Brain
      Tumor: A Case Report.
AB  - Neuropathic pain is usually managed pharmacologically, rather than with botulinum
      toxin type A (BTX-A). However, medications commonly fail to relieve pain
      effectively or have intolerable side effects. We present the case of a 62-year
      old man diagnosed with an intracranial chondrosarcoma, which was removed
      surgically and treated with radiation therapy. He suffered from neuropathic pain
      despite combined pharmacological therapy with gabapentin, amitriptyline,
      tramadol, diazepam, and duloxetine because of adverse effects. BTX-A (100 units)
      was injected subcutaneously in the most painful area in the posterior left thigh.
      Immediately after the injection, his pain decreased significantly from 6/10 to
      2/10 on a visual analogue scale. Pain relief lasted for 12 weeks. This case
      report describes intractable neuropathic pain caused by a brain tumor that was
      treated with subcutaneous BTX-A, which is a useful addition for the management of
      neuropathic pain related to a brain tumor.

PMID- 29354589
TI  - Collet-Sicard Syndrome With Hypoglossal Nerve Schwannoma: A Case Report.
AB  - Collet-Sicard syndrome is a rare syndrome that involves paralysis of 9th to 12th
      cranial nerves. We report an uncommon case of schwannoma of the hypoglossal nerve
      in a 39-year-old woman presented with slurred speech, hoarse voice, and
      swallowing difficulty. Physical examination revealed decreased gag reflex on the
      right side, decreased laryngeal elevation, tongue deviation to the right side,
      and weakness of right trapezius muscle. MRI revealed a mass lesion in the right
      parapharyngeal space below the jugular foramen. The tumor was surgically removed.
      It was confirmed as hypoglossal nerve schwannoma via pathologic examination.
      Videofluoroscopic swallowing study revealed aspiration of liquid food and severe
      bolus retention in the vallecula and piriform sinus. Laryngoscopy revealed right
      vocal cord palsy. Electrodiagnostic study revealed paralysis of the right 11th
      cranial nerve. In summary, we report an uncommon case of schwannoma of the
      hypoglossal nerve with 9th to 12th cranial nerve palsy presenting as Collet
      Sicard syndrome.

PMID- 29354590
TI  - Conservative management of a dentigerous cyst associated with eruption of teeth
      in a 7-year-old girl: a case report.
AB  - Dentigerous cysts are benign odontogenic cysts that are related to the crowns of
      permanent teeth. The lesion in this study was detected in a routine panoramic
      radiograph that revealed a well-defined osteolytic lesion that measured 2.5 cm in
      diameter, with the crown of the mandibular permanent second premolar displaced to
      the lower border of the mandible. The apex of the tooth was still open. The aim
      of this article was to report the case of a 7-year-old girl with a dentigerous
      cyst associated with the tooth buds of premolars. The therapeutic approach
      consisted of extraction of the primary molar and marsupialization of the lesion.
      After 40 months of follow-up, spontaneous eruption of the impacted premolar was
      observed. In conclusion, marsupialization can be the first treatment choice for
      conservative management of dentigerous cysts in pre-adolescents.

PMID- 29354591
TI  - Unusual complications caused by lipoma of the tongue.
AB  - Lipoma is the most common, benign, soft tissue, mesenchymal tumour and is
      composed of mature adipose tissue. It is infrequent in the oral cavity
      (approximately 0.3% of all tongue neoplasias). We describe the case of a 68-year
      old man with a swelling at the tongue edge and tongue dysesthesia. Medical
      history, clinical assessment, radiographic images, and cytological analysis
      enabled specialists to classify this neoplasia as a lipoma. The patient recovered
      fully after surgical excision of the affected area, and the neuralgic symptoms
      regressed. Surgical excision is an elective treatment; however, accurate
      differential diagnosis, histological examination, and follow-up are required.

PMID- 29354593
TI  - Squamous cell carcinoma from oral lichen planus: a case report of a lesion with
      28 years of evolution.
AB  - Lichen planus (LP) is a relatively common mucocutaneous disease with autoimmune
      etiology. Considering its malignancy potential, it is important to define the
      correct diagnosis, treatment, and clinical follow-up for patients with LP so that
      the disease is not diagnosed late, thus hindering the chances of curing the
      disease. This study aims to describe a clinical case of oral squamous cell
      carcinoma, potentially originated from LP. The patient is undergoing clinical and
      histopathological follow-up. A 64-year-old Caucasian male patient presented with
      a proliferative verrucous lesion on the tongue and sought treatment at the School
      of Dentistry, University of Passo Fundo (UPF), Passo Fundo, Brazil. He claimed
      the lesion had been present since 1988, and had been initially diagnoses as "oral
      lichen planus." The physical exam presented three diagnostic hypotheses: plaque
      like oral LP, verrucous carcinoma, and squamous cell carcinoma. After incisional
      biopsy and histopathological analysis, squamous cell carcinoma was diagnosed,
      probably originating from oral LP. The case study shows that malignancy from oral
      LP is possible, which justifies periodic clinical and histopathological follow
      up, as well as the elimination of risk factors for carcinoma in patients with
      oral LP.

PMID- 29354592
TI  - Persistent lingual paresthesia caused by a displaced tooth fragment: a case
      report and literature review.
AB  - Accidental displacement of the third molar tooth or its fragment into the
      anatomical spaces is a rare but potentially serious complication. The most common
      sites of mandibular third molar displacement are the sublingual, submandibular,
      and pterygomandibular spaces. Removal of a displaced tooth or its fragments from
      these spaces may be difficult due to poor access and the vital structures
      involved in these spaces; therefore, removal may result in permanent damage. This
      article is intended to provide a concise update of the reported cases of
      submandibular displacement and to present a case of intraoral management of
      mandibular third molar root fragments that were displaced into the submandibular
      space.

PMID- 29354594
TI  - Surgical correction of grade III hypertelorism.
AB  - Orbital hypertelorism is an increased distance between the bony orbits and can be
      caused by frontonasal malformations, craniofacial clefts, frontoethmoidal
      encephaloceles, glial tumors or dermoid cysts of the root of the nose, and
      various syndromic or chromosomal disorders. We report a series of 7 cases of
      hypertelorism that were treated in our hospital. The underlying causes in our
      series were craniofacial clefts 0 to 14 (4 cases), craniofacial clefts 1 to 12 (1
      case), and frontonasal encephalocele (2 cases), all congenital. Surgical
      techniques used to correct the deformity were box osteotomy and medial wall
      osteotomy with or without calvarial and rib grafts. A few of our cases were
      reoperations with specific challenges.

PMID- 29354595
TI  - Synergistic Rescue of Nonsense Mutant Tumor Suppressor p53 by Combination
      Treatment with Aminoglycosides and Mdm2 Inhibitors.
AB  - The tumor suppressor gene TP53 is inactivated by mutation in a large fraction of
      human tumors. Around 10% of TP53 mutations are nonsense mutations that lead to
      premature termination of translation and expression of truncated unstable and non
      functional p53 protein. Aminoglycosides G418 (geneticin) and gentamicin have been
      shown to induce translational readthrough and expression of full-length p53.
      However, aminoglycosides have severe side effects that limit their clinical use.
      Here, we show that combination treatment with a proteasome inhibitor or compounds
      that disrupt p53-Mdm2 binding can synergistically enhance levels of full-length
      p53 upon aminoglycoside-induced readthrough of R213X nonsense mutant p53. Full
      length p53 expressed upon combination treatment is functionally active as
      assessed by upregulation of p53 target genes, suppression of cell growth, and
      induction of cell death. Thus, our results demonstrate that combination treatment
      with aminoglycosides and compounds that inhibit p53 degradation is synergistic
      and can provide significantly improved efficacy of readthrough when compared with
      aminoglycosides alone. This may have implications for future cancer therapy based
      on reactivation of nonsense mutant TP53.

PMID- 29354596
TI  - The Journal of Comorbidity affiliates with the North American Primary Care
      Research Group.

PMID- 29354597
TI  - Development of a research tool to document self-reported chronic conditions in
      primary care.
AB  - Background: Researchers interested in multimorbidity often find themselves in the
      dilemma of identifying or creating an operational definition in order to generate
      data. Our team was invited to propose a tool for documenting the presence of
      chronic conditions in participants recruited for different research studies.
      Objective: To describe the development of such a tool. Design: A scoping review
      in which we identified relevant studies, selected studies, charted the data, and
      collated and summarized the results. The criteria considered for selecting
      chronic conditions were: (1) their relevance to primary care services; (2) the
      impact on affected patients; (3) their prevalence among the primary care users;
      and (4) how often the conditions were present among the lists retrieved from the
      scoping review. Results: Taking into account the predefined criteria, we
      developed a list of 20 chronic conditions/categories of conditions that could be
      self-reported. A questionnaire was built using simple instructions and a table
      including the list of chronic conditions/categories of conditions. Conclusions:
      We developed a questionnaire to document 20 self-reported chronic
      conditions/categories of conditions intended to be used for research purposes in
      primary care. Guided by previous literature, the purpose of this questionnaire is
      to evaluate the self-reported burden of multimorbidity by participants and to
      encourage comparability among research studies using the same measurement.

PMID- 29354600
TI  - Peripheral and endometrial dendritic cell populations during the normal cycle and
      in the presence of endometriosis.
AB  - Background: Dysfunctional immune response may be implicated in endometriosis
      pathogenesis, and dendritic cells (DC) may play greater roles in this response
      than previously recognized. This study set out to evaluate peripheral blood and
      endometrial DC population changes in the presence and absence of endometriosis
      pathology. Methods: Endometrial (n = 83) and peripheral blood samples (n = 30)
      were subjected to immunohistochemical techniques and flow cytometry,
      respectively, to assess DC populations in women with and without endometriosis.
      Three circulating DC subsets (MDC1, MDC2 and PDC, expressing CD1c, CD303 and
      CD141), and late-stage mature endometrial DCs (using DC-LAMP antibody) were
      investigated. Results: A highly significant reduction in CD1c intensity on MDC1
      populations in peripheral blood was observed between normal cycle proliferative
      and menstrual phases (p = 0.025), but not in women with endometriosis, in whom
      CD1c intensity was markedly increased at the time of menstruation (p = 0.05). A
      significant reduction in peripheral blood MDC2 (p = 0.016) and apparent reduction
      in endometrial DC-LAMP+ DC (trend, p = 0.062) were observed in women with
      endometriosis compared with controls, consistent with our preliminary DC data.
      Conclusions: Cyclical variation in endometrial and circulating DC populations
      appears to be crucial during normal menstrual cycles and in the establishment of
      pregnancy. In endometriosis, circulating and endometrial DC populations are
      significantly dysregulated at a number of levels, and are likely to contribute to
      inefficient immunological targeting of endometrial fragments shed at
      menstruation, facilitating their survival and establishment of endometriosis.

PMID- 29354601
TI  - Laterality: Right-Sided and Left-Sided Colon Cancer.

PMID- 29354598
TI  - Immunomodulatory Effects of Amblyomma variegatum Saliva on Bovine Cells:
      Characterization of Cellular Responses and Identification of Molecular
      Determinants.
AB  - The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary
      importance and is considered as one of major pest of ruminants in Africa and in
      the Caribbean. It causes direct skin lesions, transmits heartwater, and
      reactivates bovine dermatophilosis. Tick saliva is reported to affect overall
      host responses through immunomodulatory and anti-inflammatory molecules, among
      other bioactive molecules. The general objective of this study was to better
      understand the role of saliva in interaction between the Amblyomma tick and the
      host using cellular biology approaches and proteomics, and to discuss its impact
      on disease transmission and/or activation. We first focused on the immuno
      modulating effects of semi-fed A. variegatum female saliva on bovine peripheral
      blood mononuclear cells (PBMC) and monocyte-derived macrophages in vitro. We
      analyzed its immuno-suppressive properties by measuring the effect of saliva on
      PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC
      lymphoproliferation. We then studied the effect of saliva on bovine macrophages
      using flow cytometry to analyze the expression of MHC-II and co-stimulation
      molecules (CD40, CD80, and CD86) and by measuring the production of nitric oxide
      (NO) and pro- or anti-inflammatory cytokines. We observed a significant decrease
      in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased
      levels of IL-12-p40 and TNF-alpha and increased level of IL-10, which could
      explain the saliva-induced modulation of NO. To elucidate these immunomodulatory
      effects, crude saliva proteins were analyzed using proteomics with an Orbitrap
      Elite mass spectrometer. Among the 336 proteins identified in A. variegatum
      saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno
      modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme
      lipoprotein). We also characterized an intriguing ubiquitination complex that
      could be involved in saliva-induced immune modulation of the host. We propose a
      model for the interaction between A. variegatum saliva and host immune cells that
      could have an effect during tick feeding by favoring pathogen dissemination or
      activation by reducing the efficiency of host immune response to the
      corresponding tick-borne diseases.

PMID- 29354602
TI  - The Future Medical Science and Colorectal Surgeons.
AB  - Future medical technology breakthroughs will build from the incredible progress
      made in computers, biotechnology, and nanotechnology and from the information
      learned from the human genome. With such technology and information, computer
      aided diagnoses, organ replacement, gene therapy, personalized drugs, and even
      age reversal will become possible. True 3-dimensional system technology will
      enable surgeons to envision key clinical features and will help them in planning
      complex surgery. Surgeons will enter surgical instructions in a virtual space
      from a remote medical center, order a medical robot to perform the operation, and
      review the operation in real time on a monitor. Surgeons will be better than
      artificial intelligence or automated robots when surgeons (or we) love patients
      and ask questions for a better future. The purpose of this paper is looking at
      the future medical science and the changes of colorectal surgeons.

PMID- 29354599
TI  - The Toolbox for Uncovering the Functions of Legionella Dot/Icm Type IVb Secretion
      System Effectors: Current State and Future Directions.
AB  - The defective in organelle trafficking/intracellular multiplication (Dot/Icm)
      Type IVb secretion system (T4SS) is the essential virulence factor for the
      intracellular life style and pathogenicity of Legionella species. Screens
      demonstrated that an individual L. pneumophila strain can use the Dot/Icm T4SS to
      translocate an unprecedented number of more than 300 proteins into host cells,
      where these, so called Icm/Dot-translocated substrates (IDTS) or effectors,
      manipulate host cell functions to the benefit of the bacteria. Bioinformatic
      analysis of the pan-genus genome predicts at least 608 orthologous groups of
      putative effectors. Deciphering the function of these effectors is key to
      understanding Legionella pathogenesis; however, the analysis is challenging.
      Substantial functional redundancy renders classical, phenotypic screening of
      single gene deletion mutants mostly ineffective. Here, I review experimental
      approaches that were successfully used to identify, validate and functionally
      characterize T4SS effectors and highlight new methods, which promise to
      facilitate unlocking the secrets of Legionella's extraordinary weapons arsenal.

PMID- 29354603
TI  - Is the Location of the Tumor Another Prognostic Factor for Patients With Colon
      Cancer?
AB  - Purpose: In this study, we investigated both the characteristics of right colon
      cancer (RTCC) in comparison with those of left colon cancer (LTCC) and the impact
      of the location of the colon cancer on the prognosis. Methods: We retrospectively
      analyzed the cases of 974 patients with nonmetastatic colon cancer who had
      undergone surgery with a curative intent from January 2001 to December 2011. RTCC
      was defined as a tumor located proximal to the splenic flexure. The
      characteristics of RTCC cancer were investigated by using descriptive analyses,
      and their impacts on the prognosis were assessed by using a Cox multivariate
      regression. Results: Compared to LTCC, RTCC showed a female-dominant feature, and
      an undifferentiated pathology was more frequently observed. The number of lymph
      nodes retrieved from patients with RTCC was significantly higher than that
      retrieved from patients with LTCC. During 75 months of follow-up, peritoneal
      recurrence was more common in patients with RTCC than it was in patients with
      LTCC, and among the patients with stage III colon cancer, the disease-free and
      the overall survival rates were significantly worse in patients with RTCC. After
      adjustments with the other prognostic factors associated with colon cancer had
      been made, a tumor located at the right colon was found to be independently
      associated with poor prognosis. Conclusion: RTCC showed unique clinicopathologic
      features and was associated with a poorer prognosis.

PMID- 29354604
TI  - Difference in Tumor Area as a Predictor of a Pathological Complete Response for
      Patients With Locally Advanced Rectal Cancer.
AB  - Purpose: This study was conducted to discover the clinical factors that can
      predict pathologically complete remission (pCR) after neoadjuvant
      chemoradiotherapy (CRT), so that those factors may help in deciding on a
      treatment program for patients with locally advanced rectal cancer. Methods: A
      total of 137 patients with locally advanced rectal cancer were retrospectively
      enrolled in this study, and data were collected retrospectively. The patients had
      undergone a total mesorectal excision after neoadjuvant CRT. Histologic response
      was categorized as pCR vs. non-pCR. The tumor area was defined as (tumor length)
      * (maximum tumor depth). The difference in tumor area was defined as pre-CRT
      tumor area - post-CRT tumor area. Univariate and multivariate logistic regression
      analyses were conducted to find the factors affecting pCR. A P-value < 0.05 was
      considered significant. Results: Twenty-three patients (16.8%) achieved pCR. On
      the univariate analysis, endoscopic tumor circumferential rate <50%, low pre-CRT
      T & N stage, low post-CRT T & N stage, small pretreatment tumor area, and large
      difference in tumor area before and after neoadjuvant CRT were predictive factors
      of pCR. A multivariate analysis found that only the difference in tumor area
      before and after neoadjuvant CRT was an independent predictor of pCR (P < 0.001).
      Conclusion: The difference in tumor area, as determined using radiologic tools,
      before and after neoadjuvant CRT may be important predictor of pCR. This clinical
      factor may help surgeons to determine which patients who received neoadjuvant CRT
      for locally advanced rectal cancer should undergo surgery.

PMID- 29354605
TI  - Which One is Better? Comparison of the Acute Inflammatory Response, Raja Isteri
      Pengiran Anak Saleha Appendicitis and Alvarado Scoring Systems.
AB  - Purpose: Acute appendicitis (AA) is one of the most common causes of an acute
      abdomen. The accuracies of the Alvarado and the acute inflammatory response (AIR)
      scores in the diagnosis of appendicitis is very low in Asian populations, so a
      new scoring system, the Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA)
      system, was designed recently. We applied and compared the Alvarado, AIR, and
      RIPASA scores in the diagnoses of appendicitis in the Iranian population.
      Methods: We prospectively compared the RIPASA, Alvarado, and AIR systems by
      applying them to 100 patients. All the scores were calculated for patients who
      presented with right quadrant pain. Appendectomies were performed; then, the
      postoperative pathology reports were correlated with the scores. Scores of 8, 7,
      and 5 or more are optimal cutoffs for the RIPASA, Alvarado, and AIR scoring
      systems, respectively. The sensitivities, specificities, positive predictive
      values, negative predictive values (NPVs), positive and negative likelihood
      ratios (LRs) for the 3 systems were determined. Results: The sensitivity and the
      specificity of the RIPASA score were 93.18% and 91.67%, respectively. The
      sensitivities of the Alvarado and the AIR scores were both 78.41%. The
      specificities of the Alvarado and the AIR scores were 100% and 91.67%,
      respectively. The RIPASA score correctly classified 93% of all patients confirmed
      with histological AA compared with 78.41% for the Alvarado and the AIR scores.
      Conclusion: The RIPASA scoring system had more sensitivity, better NPV, a
      positive LR, and a less negative LR for the Iranian population whereas the
      Alvarado scoring system was more specific.

PMID- 29354606
TI  - Clinical Significance of Signet-Ring-Cell Colorectal Cancer as a Prognostic
      Factor.
AB  - Purpose: The aim of this study is to evaluate the prognosis for patients with a
      signet-ring-cell carcinoma (SRCC) who undergo curative surgery by comparing them
      to patients with an adenocarcinoma (ADC), excluding a mucinous ADC. Methods:
      Between September 1994 and December 2013, 14,110 patients with colorectal cancer
      underwent surgery and among them, 12,631 patients were enrolled in this study. 71
      patients with a SRCC and 12,570 patients with a ADC were identified. We analyzed
      the disease-free survival and the overall survival rates before and after a 1:2
      propensity score matching and evaluated those rates after stage stratification.
      Results: The median follow-up durations were 48.5 months for the SRC group and
      48.6 months for the ADC group. The disease-free survival rates and the overall
      survival rates were significantly lower in the SRC group before and after
      propensity score matching (P < 0.001). After stratification by stage, no
      differences were observed between the SRC and the ADC groups for the disease-free
      survival (DFS) and the overall survival (OS) rates for patients with cancer in
      its early stages (P = 0.913 and P = 0.380 for the DFS and the OS, respectively,
      in stages 0 and I, and P = 0.223 and P = 0.991 for the DFS and the OS,
      respectively, in stage II), but those rates were significantly lower in the SRC
      group for cancer in its later stages (P < 0.001, respectively in stages III and
      IV). Conclusion: For cancer in advanced stages, patients with a resectable
      colorectal SRCC had a poorer prognosis after propensity score matching than those
      with an ADC did. Therefore, more intensive surveillance and closer observation
      should be offered to such patients.

PMID- 29354607
TI  - Surgical Outcomes and Risk Factors in Patients Who Underwent Emergency Colorectal
      Surgery.
AB  - Purpose: Emergency colorectal surgery has high rates of complications and
      mortality because of incomplete bowel preparation and bacterial contamination.
      The authors aimed to evaluate the surgical outcomes and the risk factors for the
      mortality and the complication rates of patients who underwent emergency surgery
      to treat colorectal diseases. Methods: This is a prospective study from January
      2014 to April 2016, and the results are based on a retrospective analysis of the
      clinical results for patients who underwent emergency colorectal surgery at
      Chosun University Hospital. Results: A total of 99 patients underwent emergency
      colorectal surgery during the study period. The most frequent indication of
      surgery was perforation (75.8%). The causes of disease were colorectal cancer
      (19.2%), complicated diverticulitis (21.2%), and ischemia (27.2%). There were 27
      mortalities (27.3%). The major morbidity was 39.5%. Preoperative hypotension and
      perioperative blood transfusion were independent risk factors for both morbidity
      and mortality. Conclusion: These results revealed that emergency colorectal
      surgeries are associated with significant morbidity and mortality. Furthermore,
      the independent risk factors for both morbidity and mortality in such patiients
      were preoperative hypotension and perioperative transfusion.

PMID- 29354608
TI  - A Granular Cell Tumor of the Rectum: A Case Report and Review of the Literature.
AB  - A granular cell tumor (GCT) is an uncommon mesenchymal lesion that rarely occurs
      in the colon and the rectum. We describe the case of 51-year-old man with a 2-cm
      sized rectal GCT 10 cm above the anal verge that was incidentally detected after
      a screening colonoscopy. Preoperative radiologic studies demonstrated a
      suspicious submucosal rectal mass with mesorectal fat infiltration, but without
      circumferential resection margin threatening, extramural vessel invasion, and
      regional lymph-node enlargement. The tumor was resected by using a transanal
      endoscopic operation (TEO) without immediate postoperative complications. The
      final pathology revealed that the tumor consisted of a GCT that had invaded the
      subserosa with clear margins. It had no other risk factors for malignancy
      according to Fanburg-Smith criteria. We systematically reviewed the English
      literature by using PubMed and Google Scholar. This report may be the first
      documented case in the literature to describe a TEO for a GCT that had invaded
      the subserosa in the rectum.

PMID- 29354609
TI  - Side-to-Side Ileosigmoidostomy Shunting Surgery for the Treatment of Elderly
      Patients With Chronic Constipation.
AB  - Constipation is a digestive disorder that often occurs in the elderly; its main
      cause is bowel motility disorder. Treatments for patients with chronic
      constipation include pharmacotherapy, diet changes, and surgery if other
      therapies do not offer satisfactory results. We describe 4 patients, 2 men (70
      and 65 years old) and 2 women (75 and 66 years old), who were diagnosed with
      chronic constipation (slow transit constipation) and treated with conventional
      therapy, but did not improve. For that reason, side-to-side ileosigmoidostomy
      shunting surgery was performed. After the surgery, the average time until normal
      defecation was 16 days, and the defecation frequency was 3 to 4 times a day with
      no need for a laxative. No patient had a recurrence of constipation. Based on
      these results, side-to-side ileosigmoidostomy shunting surgery is expected to
      restore digestive function and can be considered as an alternative therapy for
      elderly patients with chronic constipation.

PMID- 29354610
TI  - Corrigendum: Correction of the Fourth Author's Affiliation. Synthetic Versus
      Biological Mesh-Related Erosion After Laparoscopic Ventral Mesh Rectopexy: A
      Systematic Review.
AB  - [This corrects the article on p. 46 in vol. 33, PMID: 28503515.].

PMID- 29354611
TI  - Corrigendum: Correction of the First Author's Affiliation. Outcome of Colorectal
      Surgery in Elderly Populations.
AB  - [This corrects the article on p. 139 in vol. 32, PMID: 27626024.].

PMID- 29354612
TI  - Probiotics in the Prevention and Treatment of Postmenopausal Vaginal Infections:
      Review Article.
AB  - Bacterial vaginosis (BV) and complicated vulvovaginal candidiasis (VVC) are
      frequently occurring vaginal infections in postmenopausal women, caused by an
      imbalance in vaginal microflora. Postmenopausal women suffer from decreased
      ovarian hormones estrogen and progesterone. A normal, healthy vaginal microflora
      mainly comprises Lactobacillus species (spp.), which act beneficially as a
      bacterial barrier in the vagina, interfering with uropathogens. During
      premenopausal period, estrogen promotes vaginal colonization by lactobacilli that
      metabolizing glycogen and producing lactic acid, and maintains intravaginal
      health by lowering the intravaginal pH level. A lower vaginal pH inhibits
      uropathogen growth, preventing vaginal infections. Decreased estrogen secretion
      in postmenopausal women depletes lactobacilli and increases intravaginal pH,
      resulting in increased vaginal colonization by harmful microorganisms (e.g.,
      Enterobacter, Escherichia coli, Candida, and Gardnerella). Probiotics positively
      effects on vaginal microflora composition by promoting the proliferation of
      beneficial microorganisms, alters the intravaginal microbiota composition,
      prevents vaginal infections in postmenopausal. Probiotics also reduce the
      symptoms of vaginal infections (e.g., vaginal discharge, odor, etc.), and are
      thus helpful for the treatment and prevention of BV and VVC. In this review
      article, we provide information on the intravaginal mechanism of postmenopausal
      vaginal infections, and describes the effectiveness of probiotics in the
      treatment and prevention of BV and VVC.

PMID- 29354613
TI  - The Clinical Effects of Dendropanax Morbifera on Postmenopausal Symptoms: Review
      Article.
AB  - Postmenopausal women aged 50s generally experience gradual changes in body such
      as decline in antioxidant and estrogen levels as the body ages. To overcome these
      aging-associated changes, the needs for health functional foods are increasing.
      Dendropanax morbifera (DM) have antioxidant effects, anti-inflammatory against
      cancer cells, antidiabetic, and antiatherogenic effect which are associated with
      postmenopausal symptoms. We analyzed clinical effects of DM on aging-related
      symptoms by reporting their antioxidant, anticancer and inflammatory activity,
      etc. and their bioactivity. Data sources EMBASE, SCOPUS, PubMed, Web of Science,
      and Google Scholar databases were searched up to August 2016 for studies
      investigating medicinal plants in prevention and treatment of diabetes. The
      search terms were "Dendropanax morbifera". The reference lists of articles were
      also reviewed for additional relevant studies. Extracts of DM have various
      efficacy such as antioxidant, anti-cancer, anti-inflammatory activity and anti
      thrombotic effect.

PMID- 29354614
TI  - Role Identification of Passiflora Incarnata Linnaeus: A Mini Review.
AB  - Some species of traditional herbal medicine has a history of use, most
      traditional natural herbs have been used for various diseases such as diabetes,
      hypertension, and obesity. Among them, Passiflora incarnata L. is a traditional
      natural medicine, flowers as well as berries, roots, and leaves have been used as
      a medicine. It has been used as a natural medicine for the treatment of insomnia
      and anxiety for a longtime in Europe, and it has been used primarily for sedation
      tea in North America. Moreover, Passiflora incarnata L. is widely used anti
      asthmatic, analgesic and sedation in Brazil. In other words, Passiflora incarnata
      L. has been used to treat a sedative, dysmenorrhea, insomnia, cancer, etc. in
      many countries. Present review of the plants showed a wide range of
      pharmacological activity in anxiolytic relax the clinical disease, such as anti
      inflammatory, anxiety and antioxidant. In addition, Passiflora incarnata L.
      affects menopause symptoms such as vasomotor symptoms, insomnia, and depression.
      This review aims to provide the latest information on specific functional
      components of Passiflora incarnata L. especially the results of clinical trials
      will provide new insights into opportunities for the future development of
      natural medicines and doors will be used for purposes of analysis.

PMID- 29354615
TI  - Effect of Phytoestrogen on Depression and Anxiety in Menopausal Women: A
      Systematic Review.
AB  - Objectives: In this systematic review, the effectiveness of herbal medicines in
      improving depression and anxiety in menopausal women was assessed. Methods: Three
      following databases were individually searched: MEDLINE (1966-March 2017), SCOPUS
      (1990-March 2017), and the Cochrane Library (Cochrane Central Register of
      Controlled Trials; 2017). Results: A total of 9 trials were included in this
      systematic review. Overall, soy was found to have a beneficial effect. Also,
      fennel had a significant positive effect on menopausal women with depression and
      anxiety disorder, but not on healthy women. Red clover showed varying effects
      ranging from significant to non-significant on depression and anxiety. Moreover,
      kava was found to have a significant beneficial effect on depression and anxiety
      at dose of 200 mg/days. Conclusions: Our study demonstrated that herbal medicines
      could improve anxiety and depression in among menopausal women. However, the
      beneficial effect still remains indefinite due to the poor methodology.

PMID- 29354616
TI  - The Effect of Foeniculum Vulgare (Fennel) on Body Composition in Postmenopausal
      Women with Excess Weight: A Double-blind Randomized Placebo-controlled Trial.
AB  - Objectives: The goal of this study was to evaluate the effect of fennel on body
      composition. Methods: This study is a secondary analysis of a double-blind,
      randomized, placebo-controlled trial. Fifty-four out of 60 patients were able to
      successfully complete the original study. Seven out of 54 patients were excluded
      because they were not overweight and obese. Thus, 47 women were included in this
      secondary analysis. Of these 47 women, 22 were in the fennel group and 25 were in
      placebo group. Body weight, body mass index (BMI) as well as fat distribution was
      measured at the baseline and after a three-month follow-up. Results: Comparison
      of fennel and placebo groups did not reveal any significant effect in terms of
      body weight, BMI, waist and hip circumferences and fat distribution. Also, the
      results of paired t-test did not variation of these parameters across groups
      before and after 12-week treatment. Conclusions: Menopausal women in fennel group
      experienced a slight increase in body weight and fat distribution, which was not
      significant. Further studies with larger sample sizes are recommended to validate
      the results of this study.

PMID- 29354617
TI  - Depression and Quality of Life among Postmenopausal Women in Bangladesh: A Cross
      sectional Study.
AB  - Objectives: The aims of the research are to examine the problems of abnormal
      menopausal women: the relationship between depression and menopausal-specific
      quality of life (MENQOL)-symptoms among postmenopausal women; the association of
      MENQOL-symptoms between pre- and postmenopausal female society in Bangladeshi
      real community. Methods: This cross sectional study was conducted on 435 women of
      Tangail, aged (>= 17) years, using a structured questionnaire where is inaacluded
      the information of MENQOL and one of the main outcomes "depression" is measured
      by beck depression inventory. Results: Menopausal status and MENQOL symptoms
      (except pain) are significantly (P < 0.05) associated. By using post-hoc
      analysis, the proportion of menopausal women, classified as having a depressive
      mood of early menopause is significantly higher than natural-menopause. Among
      postmenopausal women, there is a significant correlation between "concentration
      problem" and "depression". Here mean depression score (29.40 +/- 6.42) of
      menopausal women who have any difficulty in concentrating is higher than mean
      depression score (20.89 +/- 6.64) of menopausal women who have no difficulty in
      concentrating. Another six factors (osteoporosis, heart-beating, fatigue,
      pressure, tingling, headaches) of MENQOL-symptoms were significantly correlated
      with depression and P-values are 0.000, 0.000, 0.000, 0.033, 0.006, and 0.002,
      respectively. Finally the presence of "difficulty in concentrating" and "fatigue"
      are strongly associated factors with depression score (P < 0.001). Conclusions:
      The early postmenopausal women have to face more psychological problems (e.g.,
      depression) compare to others. Among postmenopausal women, there is no
      significant relation between depression and vasomotor symptom (e.g., hot-flashes)
      perspective to menopausal female society of Bangladesh.

PMID- 29354618
TI  - The Effect of Estrogen Replacement Therapy on Visceral Fat, Serum Glucose, Lipid
      Profiles and Apelin Level in Ovariectomized Rats.
AB  - Objectives: Ovarian hormones have been shown to regulate body weight, intra
      abdominal fat accumulation and plasma level of cytokines. The aim of this study
      was to investigate the effect of estrogen replacement therapy on visceral adipose
      tissue, plasma level of apelin, lipid profiles, and glucose in ovariectomized
      (OVX) rats. Methods: Thirty female Wistar rats were divided into OVX (n = 20) and
      sham (n = 10) groups. OVX rats were subdivided into estrogen replacement therapy
      (OVX+est; n = 10) receiving 17 beta-estradiol valerates (30 ug/kg, s.c., 5
      day/week, for eight weeks), and vehicle control group receiving sesame oil same
      as experiment group (OVX+ses oil; n = 10). After the treatments, all groups were
      sacrificed and blood samples were collected, visceral fats were taken from the
      abdominal cavity and weighed immediately. Apelin were measured using enzyme
      linked immunosorbent assay kits. Lipid profiles and glucose were measured using
      the enzymatic colorimetric method. Data were analyzed with one-way analysis of
      variance and (P < 0.05) determined as the statistical significance level.
      Results: After eight weeks, body weight, body mass index (BMI), visceral fat,
      apelin and lipid profiles (P < 0.01) were increased significantly in OVX rats
      compared to sham group. Treatment with estrogen leads to significant reduction in
      body weight and BMI (P < 0.05), there was no significant change in serum apelin
      level in OVX+est rats compared to OVX+ses. Conclusions: These results suggest
      that estradiol replacement therapy successfully attenuated some of the metabolic
      syndrome components, and apelin does not probably stand as a mediator of these
      physiological functions.

PMID- 29354619
TI  - A Study on Laparoscopic Sacral Colpopexy for Uterine Prolapse.
AB  - Objectives: We sought to describe the perioperative and postoperative adverse
      events associated with sacral colpopexy and evaluate the surgical outcome,
      complications, and benefits of laparoscopic sacral fixation for patients with
      pelvic prolapse. Methods: Ninety-two women with uterine prolapse underwent sacral
      colpopexy between January 2011 and September 2016 at Chosun University Hospital.
      Patients' electronic medical records were investigated for demographic,
      intraoperative, and postoperative data. Strict definitions were used for all
      clinically relevant adverse events. Patients' outcomes were documented with 1
      self-administered quality of life questionnaires: the Pelvic Floor Distress
      Inventory-20 focused on symptom distress. The primary analysis looking at
      perioperative and postoperative adverse events was descriptive and statistics
      were reported for all groups as n/N (%) with 95% confidence intervals for
      categorical variables and as mean +/- standard deviation and mean (range) for all
      continuous variables. Results: Their mean age was 69 +/- 8.1 years, mean follow
      up duration was 12 months, and mean operating time was 61 minutes. There were
      seven conversions due to anesthetic or surgical difficulties. Follow-up was
      performed using a telephone questionnaire and physical examination at 12 months.
      There were three cases of sacral pain with strong analgesics, one of vaginal
      erosion, two of transient urinary retentions, one of spondylitis, and two of mesh
      infection. Of the patients, 98.9% were satisfied with the surgical results, while
      none complained of sexual dysfunction or problems performing her usual
      activities. Conclusions: Laparoscopic sacral colpopexy is a feasible and highly
      effective technique that offers good long-term results with complication rates
      similar to those of open surgery with the added benefit of being minimally
      invasive.

PMID- 29354620
TI  - Prediction of Marital Satisfaction Based on Emotional Intelligence in
      Postmenopausal Women.
AB  - Objectives: This study was coperinducted with the aim of prediction of marital
      satisfaction based on emotional intelligence for postmenopausal women. Methods:
      This cross-sectional study was the descriptive-correlation and with a sample size
      of 134 people to predict marital satisfaction based on emotional intelligence for
      postmenopausal women was conducted in the Borujen city. The subjects were
      selected by convenience sampling. Data collection tools included an emotional
      intelligence questionnaire (Bar-on) and Enrich marital satisfaction
      questionnaire. Results: The results of this study showed a significant positive
      relationship between marital satisfaction and emotional intelligence (P < 0.05, r
      = 0.25). Also, regression analysis showed that emotional intelligence (beta =
      0.31) can predict positively and significantly marital satisfaction. Conclusions:
      Due to the positive relationship between emotional intelligence and marital
      satisfaction, adequacy of emotional intelligence is improved as important
      structural in marital satisfaction. So it seems that can with measuring emotional
      intelligence in reinforced marital satisfaction during menopause, done
      appropriate action.

PMID- 29354621
TI  - A Comparative Analysis of Pre- and Postmenopausal Females with Periodontitis and
      Its Response to a Non Invasive Clinical Approach.
AB  - Objectives: The influence of sex steroid hormones on periodontium can be
      knockdown with good plaque control. The aim of the present study was to evaluate
      periodontal status in pre- and postmenopausal women with periodontitis following
      non-surgical therapy. Methods: Total 60 female patients' periodontal status was
      measured by periodontal index (PRI), and oral hygiene status was measured by
      plaque index (PI). Both the parameters were measured at baseline i.e. before
      scaling and root planing and after 3 months intervals post treatment. Data were
      analyzed using SPSS version 21. Results: The mean PRI scores in premenopausal
      group were 5.68 +/- 0.64 and 2.53 +/- 0.13, and PI scores were 1.84 +/- 0.17 and
      0.91 +/- 0.13 respectively at baseline and 3 months. The mean PRI scores in
      postmenopausal group were 6.08 +/- 0.46 and 2.55 +/- 0.12, and PI scores were
      1.86 +/- 0.24 and 1.00 +/- 0.24 respectively at baseline and 3 months.
      Conclusions: There was more desirable response to non-surgical periodontal
      therapy in both the groups but not significant variation in between two groups.

PMID- 29354622
TI  - Safety and Efficacy of Catheter Direct Thrombolysis in Management of Acute
      Iliofemoral Deep Vein Thrombosis: A Systematic Review.
AB  - Purpose: Catheter direct thrombolysis (CDT) has been shown to be an effective
      treatment for deep venous thrombosis. The objective of the review is to improve
      safety and efficacy of the CDT by using ward based protocol, better able to
      predict complications and treatment outcome through monitoring of haemostatic
      parameters and clinical observation during thrombolysis procedure. Materials and
      Methods: MEDLINE, EMBASE, CENTRAL and Web of Science were searched for all
      articles on deep venous thrombosis, thrombolysis and correlations of clinical
      events (bleeding, successful thrombolysis) during thrombolysis with hemostatic
      parameters to March 2016. The risk of bias in included studies was assessed by
      Cochrane Collaboration's tool and Cochrane Risk of Bias Assessment Tool: for Non
      Randomized Studies of Interventions. Results: Twenty-four studies were included
      in the review and we found that improving safety and efficacy of CDT by using
      ward based protocol depending on eight factors; strict patient selection
      criteria, types of fibrinolytic drugs, mode of fibrinolytic drug injection,
      biochemical markers monitoring (fibrinogen, D-dimer, activated partial
      thromboplastin time, plasminogen activator inhibitor-1), timing of intervention,
      usage of intermittent pneumatic calf, ward monitoring and thrombolysis imaging
      assessment (intravascular ultrasound). These factors may help to improve safety
      and efficacy by reducing total thrombolytic drug dosage and at the same time
      ensure successful lysis. There is a marked lack of randomized controlled trials
      discussing the safety and efficacy of catheter direct thrombolysis. Conclusion:
      CDT can be performed safely and efficiently in clinical ward, providing that
      careful nursing, biochemical monitoring, proper selection and mode of infusion of
      fibrinolytic drugs, usage of Intermittent pneumatic calf and adequate
      thrombolysis imaging assessment are ensured.

PMID- 29354623
TI  - Occurrences and Results of Acute Kidney Injury after Endovascular Aortic
      Abdominal Repair?
AB  - Purpose: Acute kidney injury (AKI) is an important postoperative complication
      that may impact mortality and morbidity. The incidence of AKI after elective
      endovascular aneurysm repair (EVAR) is not known well. The aim of this study is
      to assess the incidence of AKI after elective EVAR and examine the impact of AKI.
      Materials and Methods: Data were collected and analyzed retrospectively from 78
      elective EVARs for abdominal aortic aneurysm (AAA) among 102 total cases of
      conventional EVAR performed in Inha University Hospital from 2009 to 2015. The
      primary endpoint was incidence and risk factors of AKI. Secondary endpoints
      included drop in estimated glomerular filtration rate (eGFR) and the mortality of
      AKI. Results: We included 78 patients (17 females, 21%; mean age, 73.9+/-12.5
      years; mean AAA diameter, 59.3+/-8.9 cm), 11 (14.1%) of whom developed AKI.
      Within 48 hours, those with AKI experienced a decrease in eGFR from 65.5+/-21.2
      to 51.2+/-19.6 mL/kg/1.73 m2, and those without AKI showed a change from 73.1+/
      9.2 to 74.2+/-10.7 mL/kg/1.73 m2. There were no patients who required dialysis
      during follow-up (mean, 24.2+/-18.0 months). Development of AKI was related to
      operation time (odds ratio [OR], 2.024; 95% confidence interval [CI], 1.732
      4.723; P<0.010) and contrast dose (OR, 3.192; 95% CI, 2.182-4.329; P<0.010).
      There were no differences in mortality between the 2 groups (P=0.784).
      Conclusion: The incidence of AKI after EVAR was related to operation time and
      contrast dose, but was not associated with medium-term mortality.

PMID- 29354624
TI  - Comparison of Clinical Outcomes between Surgical Repair and Endovascular Stent
      for the Treatment of Abdominal Aortic Aneurysm.
AB  - Purpose: This study was performed to compare the treatment outcomes between
      endovascular aneurysm repair (EVAR) and open surgical repair (OSR) of abdominal
      aortic aneurysms (AAAs) in a South Korean population. Materials and Methods: We
      performed a retrospective review of the medical records of 99 patients with AAAs
      who were managed at Gyeongsang National University Hospital between January 2005
      and December 2014. We reviewed the demographic characteristics and perioperative
      treatment outcomes of patients with AAA undergoing EVAR or OSR. In-hospital
      mortality and reintervention rates were assessed and compared between the EVAR
      and OSR groups. Results: In-hospital mortality was not significantly higher in
      the OSR group versus the EVAR group (3.8% vs. 8.7%, respectively, P=0.41).
      Intervention time (209.6 mins vs. 350.9 mins, P<0.001) and length of hospital
      stay (7.79 days vs. 17.46 days, P<0.001) were significantly longer in the OSR
      group vs. the EVAR group. Median follow-up time was 24.1+/-20 months for the EVAR
      group and 43.9+/-28 months for the OSR group. The cumulative rate of freedom from
      reintervention at 60 months was 62.0% for the EVAR group and 100% for the OSR
      group (P<0.001). Conclusion: EVAR was favorable in terms of intervention time and
      length of hospital stay, but the long-term durability of EVAR remains open for
      further debate.

PMID- 29354626
TI  - Intraoperative Vascular Surgical Consultation during Non-Vascular Surgeries in
      Tertiary Centers by Vascular Surgeon.
AB  - Purpose: There are many types of intraoperative consultations by vascular
      surgeons during non-vascular surgery. Therefore, we examined the current state of
      intraoperative consultations during non-vascular surgery in a single center.
      Materials and Methods: From January 2014 to December 2015, we reviewed records of
      40 patients (0.3%) who received an intraoperative consultation from a vascular
      surgeon for 10,734 non-vascular surgeries in Inha University Hospital. We
      examined patient characteristics, operative details, and clinical results.
      Results: There were 40 intraoperative vascular surgical consultations relating to
      bleeding (n=14, 35.0%), dissection from the vessel (n=13, 32.5%), arterial
      occlusion (n=10, 25.0%), and retroperitoneal approach (n=3, 7.5%). The locations
      of surgery were lower extremity (n=10, 25.0%), kidney (n=8, 20.0%), spine (n=6,
      15.0%), pelvis (n=6, 15.0%), head and neck (n=4, 10.0%), abdomen (n=4, 10.0%),
      and upper extremity (n=2, 5.0%). The methods of surgery included primary closure
      or ligation (n=17, 42.5%), end-to-end anastomosis (n=12, 30.0%), bypass (n=10,
      25.0%), thrombectomy (n=4, 10.0%), retroperitoneal approach (n=3, 7.5%), and
      embolization (n=2, 5.0%). Postoperative treatment was performed in the intensive
      care unit for 13 patients (32.5%), while 3 patients (7.5%) died following
      surgery. Conclusion: Intraoperative consultation by vascular surgeons during non
      vascular surgery occurred in approximately 0.3% of non-vascular surgeries. The
      region undergoing operation and type of surgery were variable. Therefore, it is
      necessary for vascular surgeons to have a comprehensive knowledge of vascular
      anatomy and to make rapid surgical decisions.

PMID- 29354625
TI  - Neuropsychological Outcome One Year after Carotid Revascularization: A before-and
      after Study.
AB  - Purpose: The aim of our study was to determine the clinical profile of patients
      considered cognitive 'responders' to surgery in order to establish clinical
      variables associated with a favorable cognitive performance. Materials and
      Methods: A total of 70 patients were included in the study. A well-validated,
      comprehensive standardized neurocognitive battery of tests of about 2 hours was
      administered. Patients were examined twice, 1-week before surgery and 1-year
      postoperatively. The criterion to be included in the 'responder' group was the
      following: to obtain a positive difference between post-revascularization and pre
      revascularization neuropsychological assessment >=1 standard deviation in >=2
      tests. Results: Twenty-seven patients (38.6%) were cognitive responders to
      treatment. In bivariate analysis between responders and non-responders, presence
      of atrophy (P=0.003), small vessels (P=0.577), symptoms (P=0.046), and age
      (P=0.030) were the factors statistically significant. When comparing cognitive
      performance before and after carotid revascularization, significant differences
      were observed in semantic fluency with a lower performance after 12 months
      (P=0.004, d=0.29), and in the Language index (Repeatable Battery for the
      Assessment of Neuropsychological Status) (P=0.005, d=0.34). Conclusion: Patients
      without neurological symptoms, of a younger age and without atrophy and white
      matter small vessel lesions are better cognitive responders 1-year after carotid
      revascularization.

PMID- 29354627
TI  - Vascular Complications Related to Posterior Lumbar Disc Surgery.
AB  - Purpose: To evaluate patients who underwent surgical or endovascular treatment
      after vascular injury related to posterior lumbar disc surgery. Materials and
      Methods: We retrospectively reviewed seven cases of vascular injuries (four
      lacerations, one arteriovenous fistula [AVF], and two pseudoaneurysms) related to
      lumbar disc surgery by a posterior approach from January 1997 to December 2016 at
      Chonnam National University Hospital. Information of patient characteristics,
      diagnosis, treatment strategies, and outcomes were analyzed. Results: Five out of
      seven cases were inhospital cases. In three laceration cases, each patient
      instantly became hypotensive and a life-threatening arterial injury was
      suspected. Therefore, the patient was immediately turned to the supine position
      and surgical repair was performed. The patients with pseudoaneurysm and AVF were
      treated by endovascular intervention. Remaining two were referred cases under the
      impression of vascular injuries. One laceration case of them was in preshock
      condition, and the left common iliac artery was surgically repaired. The other
      referred patient showed pseudoaneurysm which was treated with stent graft
      insertion. There was no surgery or endovascular intervention related death and
      none of the patients suffered any sequela related to vascular injury. Conclusion:
      Vascular injury associated with posterior lumbar disc surgery is not common, but
      can be fatal. Early recognition, diagnosis, and prompt treatment are essential to
      prevent fatal outcomes. Recently, endovascular intervention is increasingly and
      preferably used because of its low morbidity and mortality. However surgery is
      still the best option for the patients with unstable vital sign and endovascular
      approach can be applied to stable patients.

PMID- 29354628
TI  - Femoral Endovenectomy with Iliac Stenting for Chronic Iliofemoral Venous
      Occlusion.
AB  - A 62-year-old man with progressive swelling on his left thigh and leg was
      referred to the Division of Vascular Surgery. Anticoagulation therapy did not
      prevent or improve the symptoms of chronic deep vein thrombosis (DVT) from his
      left external iliac vein to posterior tibial vein. He had no trauma history nor
      any accidents. He underwent femoral endovenectomy, thrombectomy and stent
      insertion in left iliac vein. The patient had additional balloon angioplasty for
      stenosis in left common femoral vein. He had an uneventful postoperative recovery
      without complication. Leg swelling has been improving and follow-up continues
      under anticoagulation. We report a case of femoral endovenectomy with iliac
      stenting, which may be an efficacious treatment for chronic DVT.

PMID- 29354629
TI  - Rescue Technique for Malposition Caused by Mislabeled Stent Graft in Thoracic
      Aneurysm.
AB  - The aim of this paper is to report a salvage treatment for malpositioned stent
      graft due to mislabeled product during thoracic endovascular aortic repair
      (TEVAR) in descending thoracic aneurysm (DTA). A 78-year-old male presented with
      6.7*4.1 cm sized saccular DTA and 7.1*7.3 cm sized abdominal aortic aneurysm
      (AAA). DTA was initially treated by TEVAR and 2 months later AAA was treated by
      open aortic repair. Unfortunately, although the stent graft was correctly labeled
      for DTA, the actual size of product wrapped in a box was different contrary to
      our expectations. On completion angiography, proximal sealing zone showed no
      endoleak, however, celiac trunk and superior mesenteric artery (SMA) was found to
      be accidentally occluded. Through an emergent thoracotomy, distal part of stent
      graft was removed by cutting distal segment of stent graft and pulling out
      maneuver to restore blood flow. The completion angiography presented no endoleak,
      and celiac trunk and SMA were secured. Cutting distal segment of stent graft and
      pulling out maneuver is one of feasible rescue technique to maintain blood flow
      of occluded celiac trunk during TEVAR.

PMID- 29354630
TI  - Maternal Feeding Practices among Children with Feeding Difficulties-Cross
      sectional Study in a Brazilian Reference Center.
AB  - Background: Given the positive influence of responsive caregiving on dietary
      habits in childhood, to raise awareness of caregivers regarding their behavior is
      crucial in multidisciplinary care on infant feeding. Objectives: To identify the
      most common responsive and non-responsive feeding practices in mothers of
      children with feeding complaints, as well as to seek associations between
      practices and caregivers' profile. Methods: Cross-sectional study with 77
      children under 18 years old, with complaints of feeding difficulties. Data were
      collected during interviews with mothers: child age, gender, duration of
      exclusive breastfeeding, presence of organic disease, dynamics of bottle use,
      self-feeding practices and posture at meals, use of appropriate feeding
      equipment; basic information about the mothers (parity and level of education),
      caregiver feeding style, presence of coercive feeding, frequency and
      characteristics of family meals. Statistical analysis considered significance
      level at 5%. Results: The non-responsive profile predominated among mothers
      (76.2%, with the Authoritarian style being the most prevalent-39.7%). The
      responsive profile was characterized by absence of coercive feeding, stimulation
      of self-feeding practices, use of appropriate feeding equipment and meal
      environment, with interaction at meals. Non-responsive profile consisted of both
      inadequate environment and posture at meals, use of distraction and coercive
      feeding, lack of shared meals, and disregard for children's hunger signals. Only
      the habit of sharing meals with children was associated with mothers' profile,
      and considered a protection factor against non-responsive care (OR 0.23; 95% CI
      0.06-0.88). Both Authoritarian (p = 0.000) and indulgent mothers (p = 0.007)
      breastfed exclusively for longer time than negligent ones. There was a higher
      level of interaction with children in "responsive" parental style (OR 0.056; p =
      0.01) compared to other feeding styles. Conclusion: Results highlight the need
      for educational interventions focused on caregivers' behaviors.

PMID- 29354631
TI  - The Application of an Implementation Science Framework to Comprehensive School
      Physical Activity Programs: Be a Champion!
AB  - Comprehensive school physical activity programs (CSPAPs) have been endorsed as a
      promising strategy to increase youth physical activity (PA) in school settings. A
      CSPAP is a five-component approach, which includes opportunities before, during,
      and after school for PA. Extensive resources are available to public health
      practitioners and school officials regarding what should be implemented, but
      little guidance and few resources are available regarding how to effectively
      implement a CSPAP. Implementation science provides a number of conceptual
      frameworks that can guide implementation of a CSPAP, but few published studies
      have employed an implementation science framework to a CSPAP. Therefore, we
      developed Be a Champion! (BAC), which represents a synthesis of implementation
      science strategies, modified for application to CSPAPs implementation in schools
      while allowing for local tailoring of the approach. This article describes BAC
      while providing examples from the implementation of a CSPAP in three rural
      elementary schools.

PMID- 29354632
TI  - Mixture Design and Doehlert Matrix for the Optimization of the Extraction of
      Phenolic Compounds from Spondias mombin L Apple Bagasse Agroindustrial Residues.
AB  - In this study, we have determined, using RSM (mixture design and Doehlert
      matrix), the optimum values of the independent variables to achieve the maximum
      response for the extraction of total phenolic compounds from Spondias mombin L
      bagasse agroindustrial residues in order to preserve their antioxidant activity.
      The extraction of phenolic compounds, as well as their antioxidant capacity and
      the capacity to scavenge ABTS, was determined by the modified DPPH method at
      different periods of time, temperature, velocity of rotation and solvents
      concentration. We observed that the optimum condition for the highest antioxidant
      yield was obtained using water (60.84%), acetone (30.31%), and ethanol (8.85%) at
      30 degrees C during 20 min at 50 rpm. We have also found that the maximum yield
      of total phenolics was 355.63 +/- 9.77 (mg GAE/100 g), showing an EC50 of
      3,962.24 +/- 41.20 (g fruit/g of DPPH) and 8.36 +/- 0.30 (MUM trolox/g fruit),
      which were measured using DPPH and ABTS assays. These results suggest that RSM
      was successfully applied for optimizing the extraction of phenolics compounds
      thus preserving their antioxidant activity.

PMID- 29354633
TI  - Determination of Mineral Constituents, Phytochemicals and Antioxidant Qualities
      of Cleome gynandra, Compared to Brassica oleracea and Beta vulgaris.
AB  - The study compared mineral, chemical and antioxidant qualities of Cleome
      gynandra, a wild leafy vegetable, with two widely consumed commercial vegetables,
      Brassica oleracea and Beta vulgaris. Mineral nutrients were quantified with
      inductively coupled plasma mass spectrometry (ICP-MS), phenolic compounds using
      ultra-high performance liquid chromatography coupled to a mass spectrometer
      (UHPLC-MS) and beta-carotene and vitamin C using high performance liquid
      chromatography with a photodiode array detector (HPLC-PDA). The antioxidant
      potential was evaluated using 2,2-diphenyl-1-picryl hydrazyl (DPPH) and oxygen
      radical absorbance capacity (ORAC) assays. Cleome gynandra had highest
      concentrations of phosphorus, potassium, calcium, iron, zinc, ascorbic acid,
      total phenolics, and flavonoids; whereas sodium, magnesium, manganese, copper and
      beta-carotene were higher for B. vulgaris. The significantly higher antioxidant
      activity (P <= 0.05) exhibited by C. gynandra in comparison to the two commercial
      vegetables may be due to its significantly high levels of vitamin C and phenolic
      acids. These findings on the mineral, chemical and antioxidant properties of C.
      gynandra provide compelling scientific evidence of its potential in adding
      diversity to the diet and contributing toward the daily nutritional requirements
      of millions of people for food and nutritional security.

PMID- 29354634
TI  - Metabolism and Transcription in Cancer: Merging Two Classic Tales.
AB  - Cellular plasticity, or the ability of a cancer cell to adapt to changes in the
      microenvironment, is a major determinant of cell survival and functionality that
      require the coordination of transcriptional programs with signaling and metabolic
      pathways. In this scenario, these pathways sense and integrate nutrient signals
      for the induction of coordinated gene expression programs in cancer. This
      minireview focuses on recent advances that shed light on the bidirectional
      relationship between metabolism and gene transcription, and their biological
      outcomes in cancer. Specifically, we will discuss how metabolic changes occurring
      in cancer cells impact on gene expression, both at the level of the epigenetic
      landscape and transcription factor regulation.

PMID- 29354636
TI  - Different Mechanisms of Catalytic Complex Formation in Two L-Tryptophan
      Processing Dioxygenases.
AB  - The human heme enzymes tryptophan 2,3-dioxygenase (hTDO) and indoleamine 2,3
      dioxygenase (hIDO) catalyze the initial step in L-tryptophan (L-Trp) catabolism,
      the insertion of dioxygen into L-Trp. Overexpression of these enzymes causes
      depletion of L-Trp and accumulation of metabolic products, and thereby
      contributes to tumor immune tolerance and immune dysregulation in a variety of
      disease pathologies. Understanding the assembly of the catalytically active,
      ternary enzyme-substrate-ligand complexes is not yet fully resolved, but an
      essential prerequisite for designing efficient and selective de novo inhibitors.
      Evidence is mounting that the ternary complex forms by sequential binding of
      ligand and substrate in a specific order. In hTDO, the apolar L-Trp binds first,
      decreasing active-site solvation and, as a result, reducing non-productive
      oxidation of the heme iron by the dioxygen ligand, which may leave the substrate
      bound to a ferric heme iron. In hIDO, by contrast, dioxygen must first coordinate
      to the heme iron because a bound substrate would occlude ligand access to the
      heme iron, so the ternary complex can no longer form. Consequently, faster
      association of L-Trp at high concentrations results in substrate inhibition.
      Here, we summarize our present knowledge of ternary complex formation in hTDO and
      hIDO and relate these findings to structural peculiarities of their active sites.

PMID- 29354637
TI  - Mapping Disease Data: A Usability Test of an Internet-Based System of Disease
      Status Disclosure.
AB  - Disease maps are important tools in the management of disease. By communicating
      risk, disease maps can help raise awareness of disease and encourage farmers and
      veterinarians to employ best practice to eliminate the spread of disease.
      However, despite the importance of disease maps in communicating risk and the
      existence of various online disease maps, there are few studies that explicitly
      examine their usability. Where disease maps are complicated to use, it seems that
      they are unlikely to be used effectively. The paper outlines an attempt to create
      an open access, online, searchable map of incidents of bovine tuberculosis in
      England and Wales, and analyzes its usability among veterinarians. The paper
      describes the process of creating the map before describing the results of a
      series of usability trials. Results show the map to score highly on different
      measures of usability. However, the trials also revealed a number of social and
      technical limitations and challenges facing the use of online disease maps,
      including reputational dangers, role confusion, data accuracy, and data
      representation. The paper considers the challenges facing disease maps and their
      potential role in designing new methodologies to evaluate the effectiveness of
      disease prevention initiatives.

PMID- 29354638
TI  - A Probability Co-Kriging Model to Account for Reporting Bias and Recognize Areas
      at High Risk for Zebra Mussels and Eurasian Watermilfoil Invasions in Minnesota.
AB  - Zebra mussels (ZMs) (Dreissena polymorpha) and Eurasian watermilfoil (EWM)
      (Myriophyllum spicatum) are aggressive aquatic invasive species posing a
      conservation burden on Minnesota. Recognizing areas at high risk for invasion is
      a prerequisite for the implementation of risk-based prevention and mitigation
      management strategies. The early detection of invasion has been challenging, due
      in part to the imperfect observation process of invasions including the absence
      of a surveillance program, reliance on public reporting, and limited resource
      availability, which results in reporting bias. To predict the areas at high risk
      for invasions, while accounting for underreporting, we combined network analysis
      and probability co-kriging to estimate the risk of ZM and EWM invasions. We used
      network analysis to generate a waterbody-specific variable representing boater
      traffic, a known high risk activity for human-mediated transportation of invasive
      species. In addition, co-kriging was used to estimate the probability of species
      introduction, using waterbody-specific variables. A co-kriging model containing
      distance to the nearest ZM infested location, boater traffic, and road access was
      used to recognize the areas at high risk for ZM invasions (AUC = 0.78). The EWM
      co-kriging model included distance to the nearest EWM infested location, boater
      traffic, and connectivity to infested waterbodies (AUC = 0.76). Results suggested
      that, by 2015, nearly 20% of the waterbodies in Minnesota were at high risk of ZM
      (12.45%) or EWM (12.43%) invasions, whereas only 125/18,411 (0.67%) and
      304/18,411 (1.65%) are currently infested, respectively. Prediction methods
      presented here can support decisions related to solving the problems of imperfect
      detection, which subsequently improve the early detection of biological
      invasions.

PMID- 29354640
TI  - A Comparison of Computed Tomographic, Radiographic, Gross and Histological,
      Dental, and Alveolar Findings in 30 Abnormal Cheek Teeth from Equine Cadavers.
AB  - Background: Equine cheek teeth disorders, especially pulpar/apical infections,
      can have very serious consequences due to the frequent extension of infection to
      the supporting bones and/or adjacent paranasal sinuses. Limited studies have
      assessed the accuracy of computed tomographic (CT) imaging in the diagnosis of
      these disorders, and no study has directly compared imaging and pathological
      findings of the alveoli of diseased equine cheek teeth. Objective: To validate
      the accuracy of CT and radiographic imaging of cheek teeth disorders by comparing
      CT and radiographic imaging, gross and histological findings in abnormal cheek
      teeth and their alveoli extracted from equine cadaver heads. Study design: Ex
      vivo original study. Methods: Fifty-four cadaver heads from horses with unknown
      histories that had died or been euthanized on humane grounds obtained from a
      rendering plant had radiography, CT imaging, and gross pathological examinations
      performed. Based on imaging and gross examination findings, 30 abnormal cheek
      teeth (26 maxillary and 4 mandibular) identified in 26 heads were extracted along
      with their dental alveoli where possible, and further CT imaging, gross, and
      histological examinations were performed. Eight maxillary cheek teeth (including
      four with attached alveolar bone) from these heads, that were normal on gross and
      CT examinations, were used as controls. Results: Gross pathological and
      histological examinations indicated that 28/30 teeth, including two supernumerary
      teeth, had pulpar/apical infection, including pulpar and apical changes. A
      further supernumerary and a dysplastic tooth were also identified. Abnormal
      calcified tissue architecture was present in all three supernumerary and in the
      dysplastic tooth. CT imaging strongly indicated the presence of pulpar/apical
      infection in 27 of the 28 (96.4%) pulpar/apically infected teeth, including the
      presence of intrapulpar gas (N = 19/28), apical clubbing (N = 20), periapical
      halo (N = 4), root lysis or fragmentation (N = 7), and periapical gas (N = 2).
      Also present were alveolar bone sclerosis (N = 20), alveolar bone thickening (N =
      3), and lytic/erosive changes (N = 8). Radiographic abnormalities strongly
      indicative of pulpar/apical infection including periapical sclerosis (N = 8/28)
      and apical clubbing (N = 14/28) were found in 14/28 (50%) of apically infected
      teeth. Histological changes were present in alveolar bone of all 21 cases of
      apical infection where alveolus remained attached to the tooth and was marked in
      16 cases, all which had CT alveolar changes. Histological changes included
      disruption of the normal trabecular pattern, increased osteoclastic activity, and
      the presence of islands of bone with a scalloped profile within the thickened
      attached periodontal ligament. No gross pathological or histological changes were
      present in the eight control teeth or their alveoli (N = 4). Main limitations: No
      history or breed-related information was available on these cases. Conclusion:
      There was a 96.4% correlation between a CT diagnosis and confirmative
      pathological findings in 28 apically infected teeth confirming the accuracy of CT
      imaging in diagnosing equine pulpar/apical infections. There was also excellent
      correlation between CT and histological alveolar bone findings.

PMID- 29354639
TI  - Perspectives and Outcomes of the Activity of a Reference Laboratory for
      Brucellosis.
AB  - One health is an emerging conceptual approach geared to harmonize the activities
      of the public health, veterinary services, and extension services within a single
      operative structure. Brucellosis is an important zoonosis worldwide, mostly
      involving nomadic populations but may often affect transboundary animal
      management and exotic domesticated animal farming such as camels and buffalo.
      Here, we provide contemporary knowledge on the disease and its causative agent, a
      Gram-negative bacteria belonging to the genus Brucella. Further, because of the
      zoonotic importance, we emphasize the need to assign a national reference
      laboratory for the disease and discuss how this would integrate into a "One
      Health" system. Brucella vaccines are live attenuated strains possessing the
      smooth phenotype, and vaccination, therefore, hampers the ability to maintain a
      national surveillance program due to concerns regarding the false positive
      vaccine-induced responses. In order to overcome these failings, we developed a
      combined approach based on rapid screening of mass numbers of serum samples by
      the fluorescence polarization assay, a cost-effective and accurate method, and
      confirmation of the true positive reactors by the complement fixation test, a
      highly specific method that is less sensitive to vaccine-induced antibodies. We
      demonstrate how, despite the high vaccination coverage of the small ruminant
      population in Israel, our results proved to be effective in discriminating
      between vaccinated and infected animals. The speed and accuracy of the method
      further justified immediate declaration of 37% of flocks as cleansed from
      brucellosis, thus reducing the burden of repeated tests among this population.

PMID- 29354641
TI  - A Data Set of Human Body Movements for Physical Rehabilitation Exercises.
AB  - The article presents University of Idaho - Physical Rehabilitation Movement Data
      (UI-PRMD) - a publically available data set of movements related to common
      exercises performed by patients in physical rehabilitation programs. For the data
      collection, 10 healthy subjects performed 10 repetitions of different physical
      therapy movements, with a Vicon optical tracker and a Microsoft Kinect sensor
      used for the motion capturing. The data are in a format that includes positions
      and angles of full-body joints. The objective of the data set is to provide a
      basis for mathematical modeling of therapy movements, as well as for establishing
      performance metrics for evaluation of patient consistency in executing the
      prescribed rehabilitation exercises.

PMID- 29354642
TI  - Use of My HealtheVet patient web portal among veterans seen for diabetes mellitus
      at a medical center in the southeastern United States.
AB  - Background: An increasing number of studies have examined the use of information
      technology to improve diabetes care and patient self-management. The goal of the
      current study was to determine the number of veterans seen for diabetes at a
      large medical center in the southeastern region of the U.S. and to examine
      whether they had registered for VA's My HealtheVet patient web portal according
      to selected characteristics. Methods: Existing patient records were reviewed
      including My HealtheVet web portal registration by veterans treated for diabetes
      (ICD-10 code for type 2 diabetes) at the Charlie Norwood VAMC. Number of
      outpatient clinic patients seen for diabetes who had or had not registered for My
      HealtheVet were examined by age categories, sex, race, Hispanic ethnicity, and
      era of military service. Results: A total of 49,341 veterans receive care at the
      Charlie Norwood VAMC. Of those patients, 10,950 have been seen for diabetes. Of
      the 49,341 patients, 21,372 patients (43.3%) are using My HealtheVet and 10,465
      patients (21.2%) have used secure messages. Of 10,950 diabetic patients, only
      1,256 (11.5%) have registered for My HealtheVet. Women with diabetes were more
      likely to be registered for My HealtheVet than their male counterparts [13.92%
      vs. 11.24%; odds ratio (OR)=1.28; 95% confidence interval (CI): 1.05-1.55).
      Veterans with diabetes who served during WW II or the Korean War were less likely
      to use My HealtheVet than those who served during more recent eras (OR=0.33; 95%
      CI: 0.24-0.44). Use of the patient portal was highest among diabetic patients
      ages 51-55 years (15.6%). Conclusions: A low percentage of Veterans with diabetes
      are active users of My HealtheVet. Studies are needed to identify My HealtheVet
      portal design features and veteran characteristics that will increase use of this
      patient portal which may improve diabetes care.

PMID- 29354643
TI  - Introduction to Focused Issue on mHealth Infrastructure: issues and solutions
      that challenge optimal deployment of mHealth products and services.

PMID- 29354644
TI  - The Older Driver with Cognitive Impairment: Perceptions of Driving Ability and
      Results of a Behind the Wheel Test.
AB  - Older adult drivers with cognitive impairment pose a potential safety risk to
      themselves and others. Providers are often uncertain about when to request a
      formal evaluation of driving ability, leaving subjective reports of concerns by
      the patient or family as common initiators of objective driving evaluation
      referral. This observational study evaluated the correspondence of patient and
      caregiver report of driving concerns relative to objective behind-the-wheel (BTW)
      testing. Data were analyzed from occupational therapy driving evaluations of
      older adult U.S. Veterans referred from cognitive disorder specialty clinics
      between 2005 and 2015 (n = 151). Driving ability was evaluated with a pre-testing
      interview of the patient and a knowledgeable caregiver, followed by objective BTW
      testing. Patients referred had a mean age of 77.6 (SD = 8.1) years, were 97%
      male, and 98% white. Results demonstrated that most patients are evaluated for
      driving concerns far too late, with only 3% of the sample being evaluated as
      independent to drive without restrictions, and 38% recommended to retire from
      driving. Although both patients and caregivers denied specific driving concerns
      (obey signs and lights) relative to objective testing, caregiver concerns were
      greater than their respective patient's concerns (p < 0.001) and were associated
      with road test outcome (p = 0.001).

PMID- 29354645
TI  - A Bioactive Hydrogel and 3D Printed Polycaprolactone System for Bone Tissue
      Engineering.
AB  - In this study, a hybrid system consisting of 3D printed polycaprolactone (PCL)
      filled with hydrogel was developed as an application for reconstruction of long
      bone defects, which are innately difficult to repair due to large missing
      segments of bone. A 3D printed gyroid scaffold of PCL allowed a larger amount of
      hydrogel to be loaded within the scaffolds as compared to 3D printed mesh and
      honeycomb scaffolds of similar volumes and strut thicknesses. The hydrogel was a
      mixture of alginate, gelatin, and nano-hydroxyapatite, infiltrated with human
      mesenchymal stem cells (hMSC) to enhance the osteoconductivity and
      biocompatibility of the system. Adhesion and viability of hMSC in the
      PCL/hydrogel system confirmed its cytocompatibility. Biomineralization tests in
      simulated body fluid (SBF) showed the nucleation and growth of apatite crystals,
      which confirmed the bioactivity of the PCL/hydrogel system. Moreover, dissolution
      studies, in SBF revealed a sustained dissolution of the hydrogel with time.
      Overall, the present study provides a new approach in bone tissue engineering to
      repair bone defects with a bioactive hybrid system consisting of a polymeric
      scaffold, hydrogel, and hMSC.

PMID- 29354646
TI  - Exploring the mechanism of amebic trogocytosis: the role of amebic lysosomes.

PMID- 29354648
TI  - The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual
      blood-stage development.
AB  - The enzymes glyoxalase 1 and 2 (Glo1 and Glo2) are found in most eukaryotes and
      catalyze the glutathione-dependent conversion of 2-oxoaldehydes to 2
      hydroxycarboxylic acids. Four glyoxalases are encoded in the genome of the
      malaria parasite Plasmodium falciparum, the cytosolic enzymes PfGlo1 and PfcGlo2,
      the apicoplast enzyme PftGlo2, and an inactive Glo1-like protein that also
      carries an apicoplast-targeting sequence. Inhibition or knockout of the
      Plasmodium glyoxalases was hypothesized to lead to an accumulation of 2
      oxoaldehydes and advanced glycation end-products (AGE) in the host-parasite unit
      and to result in parasite death. Here, we generated clonal P. falciparum strain
      3D7 knockout lines for PFGLO1 and PFcGLO2 using the CRISPR-Cas9 system. Although
      3D7Deltaglo1 knockout clones had an increased susceptibility to external glyoxal,
      all 3D7Deltaglo1 and 3D7Deltacglo2 knockout lines were viable and showed no
      significant growth phenotype under standard growth conditions. Furthermore, the
      lack of PfcGlo2, but not PfGlo1, increased gametocyte commitment in the knockout
      lines. In summary, PfGlo1 and PfcGlo2 are dispensable during asexual blood-stage
      development while the loss of PfcGlo2 may induce the formation of transmissible
      gametocytes. These combined data show that PfGlo1 and PfcGlo2 are most likely not
      suited as targets for selective drug development.

PMID- 29354650
TI  - The logics of metabolic regulation in bacteria challenges biosensor-based
      metabolic engineering.
AB  - Synthetic Biology (SB) aims at the rational design and engineering of novel
      biological functions and systems. By facilitating the engineering of living
      organisms, SB promises to facilitate the development of many new applications for
      health, biomanufacturing, and the environment. Over the last decade, SB promoted
      the construction of libraries of components enabling the fine-tuning of genetic
      circuits expression and the development of novel genome engineering methodologies
      for many organisms of interest. SB thus opened new perspectives in the field of
      metabolic engineering, which was until then mainly limited to (over)producing
      naturally synthesized metabolic compounds. To engineer efficient cell factories,
      it is key to precisely reroute cellular resources from the central carbon
      metabolism (CCM) to the synthetic circuitry. This task is however difficult as
      there is still significant lack of knowledge regarding both the function of
      several metabolic components and the regulation of the CCM fluxes for many
      industrially important bacteria. Pyruvate is a pivotal metabolite at the heart of
      the CCM and a key precursor for the synthesis of several commodity compounds and
      fine chemicals. Numerous bacterial species can also use it as a carbon source
      when present in the environment but bacterial, pyruvate-specific uptake systems
      were to be discovered. This is an issue for metabolic engineering as one can
      imagine to make use of pyruvate transport systems to replenish synthetic
      metabolic pathways towards the synthesis of chemicals of interest. Here we
      describe a recent study (MBio 8(5): e00976-17), which identified and
      characterized a pyruvate transport system in the Gram-positive (G+ve) bacterium
      Bacillus subtilis, a well-established biotechnological workhorse for the
      production of enzymes, fine chemicals and antibiotics. This study also revealed
      that the activity of the two-component system (TCS) responsible for its induction
      is retro-inhibited by the level of pyruvate influx. Following up on the open
      question which is whether this retro-inhibition is a generic mechanism for TCSs,
      we will discuss the implications in metabolic engineering.

PMID- 29354635
TI  - Immunological Tolerance, Pregnancy, and Preeclampsia: The Roles of Semen Microbes
      and the Father.
AB  - Although it is widely considered, in many cases, to involve two separable stages
      (poor placentation followed by oxidative stress/inflammation), the precise
      originating causes of preeclampsia (PE) remain elusive. We have previously
      brought together some of the considerable evidence that a (dormant) microbial
      component is commonly a significant part of its etiology. However, apart from
      recognizing, consistent with this view, that the many inflammatory markers of PE
      are also increased in infection, we had little to say about immunity, whether
      innate or adaptive. In addition, we focused on the gut, oral and female urinary
      tract microbiomes as the main sources of the infection. We here marshall further
      evidence for an infectious component in PE, focusing on the immunological
      tolerance characteristic of pregnancy, and the well-established fact that
      increased exposure to the father's semen assists this immunological tolerance. As
      well as these benefits, however, semen is not sterile, microbial tolerance
      mechanisms may exist, and we also review the evidence that semen may be
      responsible for inoculating the developing conceptus (and maybe the placenta)
      with microbes, not all of which are benign. It is suggested that when they are
      not, this may be a significant cause of PE. A variety of epidemiological and
      other evidence is entirely consistent with this, not least correlations between
      semen infection, infertility and PE. Our view also leads to a series of other,
      testable predictions. Overall, we argue for a significant paternal role in the
      development of PE through microbial infection of the mother via insemination.

PMID- 29354649
TI  - Alcohols enhance the rate of acetic acid diffusion in S. cerevisiae: biophysical
      mechanisms and implications for acetic acid tolerance.
AB  - Microbial cell factories with the ability to maintain high productivity in the
      presence of weak organic acids, such as acetic acid, are required in many
      industrial processes. For example, fermentation media derived from
      lignocellulosic biomass are rich in acetic acid and other weak acids. The rate of
      diffusional entry of acetic acid is one parameter determining the ability of
      microorganisms to tolerance the acid. The present study demonstrates that the
      rate of acetic acid diffusion in S. cerevisiae is strongly affected by the
      alcohols ethanol and n-butanol. Ethanol of 40 g/L and n-butanol of 8 g/L both
      caused a 65% increase in the rate of acetic acid diffusion, and higher alcohol
      concentrations caused even greater increases. Molecular dynamics simulations of
      membrane dynamics in the presence of alcohols demonstrated that the partitioning
      of alcohols to the head group region of the lipid bilayer causes a considerable
      increase in the membrane area, together with reduced membrane thickness and lipid
      order. These changes in physiochemical membrane properties lead to an increased
      number of water molecules in the membrane interior, providing biophysical
      mechanisms for the alcohol-induced increase in acetic acid diffusion rate. n
      butanol affected S. cerevisiae and the cell membrane properties at lower
      concentrations than ethanol, due to greater and deeper partitioning in the
      membrane. This study demonstrates that the rate of acetic acid diffusion can be
      strongly affected by compounds that partition into the cell membrane, and
      highlights the need for considering interaction effects between compounds in the
      design of microbial processes.

PMID- 29354651
TI  - Risk of colorectal cancer and clotting factor gene polymorphisms in Moroccan
      Population.
AB  - Background: Venous thrombosis has been described as a common complication for
      cancer patients. The association between clotting factor gene polymorphisms and
      the risk of colorectal cancer has been evidenced. The aim of the present study
      was to investigate the association of G20210A factor II prothrombin (FII) and
      factor V Leiden ( FVL) G1691A with the risk of colorectal cancer(CRC). Methods
      and results: Genotyping of FVL and G20210A FII was performed using the polymerase
      chain reaction restriction fragment length polymorphism method on a sample of 76
      patients with CRC as well as 182 controls. No significant difference in FVL gene
      variations was observed between cases and controls. However, with regard to the
      G20210A FII, the homozygous mutated genotype AA was associated with an increased
      risk of CRC. A significant association between the G20210A FII mutation and the
      risk of CRC was identified using recessive (OR=57.63, 95% CI: 3.33-997.26,
      P=0.0053), dominant (OR=27.87, 95% CI: 12.67 -61.28, P<0, 0001) and additive
      (OR=21.24, 95% CI: 10.45-43.16, P<0, 0001) models. No statistical difference was
      observed in parameters such as sex, age and positive family history for cancer.
      Conclusion: Our results did not support an effect of FVL gene on CRC risk and
      suggested that the G20210A FII prothrombin gene variant may be a risk factor for
      CRC in Moroccan population.

PMID- 29354653
TI  - Comparison of 2D and 3D ultrasound methods to measure serial bladder volumes
      during filling: Steps toward development of non-invasive ultrasound urodynamics.
AB  - OBJECTIVES: Non-invasive methods to objectively characterize overactive bladder
      (OAB) and other forms of voiding dysfunction using real-time ultrasound are
      currently under development but require accurate and precise serial measurements
      of bladder volumes during filling. This study's objective was to determine the
      most accurate and precise ultrasound-based method of quantifying serial bladder
      volumes during urodynamics (UD). METHODS: Twelve female participants with OAB
      completed an extended UD procedure with the addition of serial bladder ultrasound
      images captured once per minute. Bladder volume was measured using three
      ultrasound methods: (1) Vspheroid: two-dimensional (2D) method calculated
      assuming spheroid geometry; (2) Vbih: 2D correction method obtained by
      multiplying Vspheroid by a previously derived correction factor of 1.375; and (3)
      V3D: three-dimensional (3D) method obtained by manually tracing the bladder
      outline in six planes automatically reconstructed into a solid rendered volume.
      These volumes were compared to a control (Vcontrol) obtained by adding UD infused
      volume and the volume of estimated urine production. RESULTS: Based on linear
      regression analysis, both Vbih and V3D were fairly accurate estimators of
      Vcontrol, but V3D was more precise. Vspheroid significantly underestimated
      Vcontrol. CONCLUSIONS: Although the Vbih and V3D methods were more accurate than
      the more-commonly used Vspheroid method for measuring bladder volumes during UD,
      the V3D method was the most precise and could best account for non-uniform
      bladder geometries. Therefore, the V3D method may represent the best tool
      required for the continued development of non-invasive methods to diagnose OAB
      and other forms of voiding dysfunction.

PMID- 29354652
TI  - Effect of Centruroides antivenom on reversal of methamphetamine-induced
      hyperkinesis and hyperthermia in rats.
AB  - Context: Methamphetamine (MA) toxicity is a major health concern causing
      agitation, hyperkinesia, hyperthermia, and even death, affecting 24.7 million
      people worldwide. It has been observed that MA generates movement disorders in
      children similar to that of scorpion envenomation. Four cases have been reported
      where MA intoxication in children were both subjectively and objectively improved
      as indicated by the reversal of nystagmus and movement disorders following
      administration of Centruroides antivenom (AV) therapy. Objective: Here, we aimed
      to demonstrate the reversal of MA induced movement disorders and hyperthermia by
      scorpion AV equine immune F(ab')2 in rats. Materials and Methods: Baseline core
      temperature and locomotor activity in adult male Sprague-Dawley rats (200-220 g)
      were evaluated prior to acute administration of AV (20 mg/kg, intraperitoneally,
      i.p.) + MA (10 mg/kg, i.p.) or control. Core body temperature was reassessed 10,
      50, and 80 min post injection while locomotor activity was reassessed 20-35 and
      60-75 min post injection. Results: At 20-35 min, Saline + MA and BSA + MA groups
      showed a significant increase in the number of fine events compared to their
      respective control groups Saline + Saline and BSA + Saline, which indicates an
      increase in paw movements of animals in situ (p = 0.008, p = 0.006,
      respectively). In contrast, AV + MA demonstrated a non-significant increase in
      fine activity compared to the control group AV + Saline). At 60-75 min, the AV +
      MA treatment group were less likely to engage in locomotor activity indicated by
      the significant decrease in exploratory events compared to BSA + MA control group
      (p = 0.041). No significant percent change in core body temperature was observed
      in the AV + MA treatment group compared to the control groups, AV + Saline and
      BSA + MA. Discussion: Here, we provide evidence for some aspects of MA-induced
      hyperkinesia but not hyperthermia reversed by scorpion AV. Further preclinical
      studies involving adolescent rodents may be necessary to completely mimic the
      reversal of MA toxicity seen in children in the clinic.

PMID- 29354654
TI  - Towards Integrating Distributed Energy Resources and Storage Devices in Smart
      Grid.
AB  - Internet of Things (IoT) provides a generic infrastructure for different
      applications to integrate information communication techniques with physical
      components to achieve automatic data collection, transmission, exchange, and
      computation. The smart grid, as one of typical applications supported by IoT,
      denoted as a re-engineering and a modernization of the traditional power grid,
      aims to provide reliable, secure, and efficient energy transmission and
      distribution to consumers. How to effectively integrate distributed (renewable)
      energy resources and storage devices to satisfy the energy service requirements
      of users, while minimizing the power generation and transmission cost, remains a
      highly pressing challenge in the smart grid. To address this challenge and assess
      the effectiveness of integrating distributed energy resources and storage
      devices, in this paper we develop a theoretical framework to model and analyze
      three types of power grid systems: the power grid with only bulk energy
      generators, the power grid with distributed energy resources, and the power grid
      with both distributed energy resources and storage devices. Based on the metrics
      of the power cumulative cost and the service reliability to users, we formally
      model and analyze the impact of integrating distributed energy resources and
      storage devices in the power grid. We also use the concept of network calculus,
      which has been traditionally used for carrying out traffic engineering in
      computer networks, to derive the bounds of both power supply and user demand to
      achieve a high service reliability to users. Through an extensive performance
      evaluation, our data shows that integrating distributed energy resources
      conjointly with energy storage devices can reduce generation costs, smooth the
      curve of bulk power generation over time, reduce bulk power generation and power
      distribution losses, and provide a sustainable service reliability to users in
      the power grid.

PMID- 29354655
TI  - Guidelines vs Actual Management of Skin and Soft Tissue Infections in the
      Emergency Department.
AB  - Background: Infections of skin and soft tissue (SSTI) commonly cause visits to
      hospital emergency departments (EDs). The Infectious Diseases Society of America
      (IDSA) has published guidelines for the management of SSTI, but it is unclear how
      closely these guidelines are followed in practice. Methods: We reviewed records
      of patients seen in the ED at a large tertiary care hospital to determine
      guidelines adherence in 4 important areas: the decision to hospitalize, choice of
      antibiotics, incision and drainage (I&D) of abscesses, and submission of
      specimens for culture. Results: The decision to hospitalize did not comply with
      guidelines in 19.6% of cases. Nonrecommended antibiotics were begun in the ED in
      71% of patients with nonpurulent infections and 68.4% of patients with purulent
      infections. Abscesses of mild severity were almost always treated with
      antibiotics, and I&D was often not done (both against recommendations). Blood
      cultures were done (against recommendations) in 29% of patients with mild
      severity cellulitis. Abscess drainage was almost always sent for culture
      (recommendations neither favor nor oppose). Overall, treatment fully complied
      with guidelines in 20.1% of cases. Conclusions: Our results show a striking lack
      of concordance with IDSA guidelines in the ED management of SSTI. Social factors
      may account for discordant decisions regarding site of care. Use of
      trimethoprim/sulfamethoxazole (TMP/SMX) in cellulitis was the most common source
      of discordance; this practice is supported by some medical literature. Excess
      antibiotics were often used in cellulitis and after I&D of simple abscesses,
      opposing antibiotic stewardship. Ongoing education of ED doctors and continued
      review of published guidelines are needed.

PMID- 29354656
TI  - Aiming at the Global Elimination of Viral Hepatitis: Challenges Along the Care
      Continuum.
AB  - A recent international workshop, organized by the authors, analyzed the obstacles
      facing the ambitious goal of eliminating viral hepatitis globally. We identified
      several policy areas critical to reaching elimination targets. These include
      providing hepatitis B birth-dose vaccination to all infants within 24 hours of
      birth, preventing the transmission of blood-borne viruses through the expansion
      of national hemovigilance schemes, implementing the lessons learned from the HIV
      epidemic regarding safe medical practices to eliminate iatrogenic infection,
      adopting point-of-care testing to improve coverage of diagnosis, and providing
      free or affordable hepatitis C treatment to all. We introduce Egypt as a case
      study for rapid testing and treatment scale-up: this country offers valuable
      insights to policy makers internationally, not only regarding how hepatitis C
      interventions can be expeditiously scaled-up, but also as a guide for how to
      tackle the problems encountered with such ambitious testing and treatment
      programs.

PMID- 29354657
TI  - Antibody and B Cell Subset Perturbations in Human Immunodeficiency Virus
      Uninfected Patients With Cryptococcosis.
AB  - The importance of antibody immunity in protection against Cryptococcus neoformans
      remains unresolved. We measured serum C neoformans-specific and total antibody
      levels and peripheral blood B cell subsets of 12 previously healthy patients with
      cryptococcosis (cases) and 21 controls. Before and after adjustment for age, sex,
      and race, cryptococcal capsular polysaccharide immunoglobulin G was higher in
      cases than controls, whereas total B and memory B cell levels were lower. These
      associations parallel previous findings in patients with human immunodeficiency
      virus-associated cryptococcosis and suggest that B cell subset perturbations may
      also associate with disease in previously normal individuals with cryptococcosis.

PMID- 29354647
TI  - Guidelines and recommendations on yeast cell death nomenclature.
AB  - Elucidating the biology of yeast in its full complexity has major implications
      for science, medicine and industry. One of the most critical processes
      determining yeast life and physiology is cel-lular demise. However, the
      investigation of yeast cell death is a relatively young field, and a widely
      accepted set of concepts and terms is still missing. Here, we propose unified
      criteria for the defi-nition of accidental, regulated, and programmed forms of
      cell death in yeast based on a series of morphological and biochemical criteria.
      Specifically, we provide consensus guidelines on the differ-ential definition of
      terms including apoptosis, regulated necrosis, and autophagic cell death, as we
      refer to additional cell death rou-tines that are relevant for the biology of (at
      least some species of) yeast. As this area of investigation advances rapidly,
      changes and extensions to this set of recommendations will be implemented in the
      years to come. Nonetheless, we strongly encourage the au-thors, reviewers and
      editors of scientific articles to adopt these collective standards in order to
      establish an accurate framework for yeast cell death research and, ultimately, to
      accelerate the pro-gress of this vibrant field of research.

PMID- 29354658
TI  - Human Immunodeficiency Virus/Hepatits C Virus Coinfection in Spain: Elimination
      Is Feasible, but the Burden of Residual Cirrhosis Will Be Significant.
AB  - Background: We assessed the prevalence of antibodies against hepatitis C virus
      (HCV-Abs) and active HCV infection in patients infected with human
      immunodeficiency virus (HIV) in Spain in 2016 and compared the results with those
      of similar studies performed in 2002, 2009, and 2015. Methods: The study was
      performed in 43 centers during October-November 2016. The sample was estimated
      for an accuracy of 2% and selected by proportional allocation and simple random
      sampling. During 2016, criteria for therapy based on direct-acting antiviral
      agents (DAA) were at least significant liver fibrosis, severe extrahepatic
      manifestations of HCV, and high risk of HCV transmissibility. Results: The
      reference population and the sample size were 38904 and 1588 patients,
      respectively. The prevalence of HCV-Abs in 2002, 2009, 2015, and 2016 was 60.8%,
      50.2%, 37.7%, and 34.6%, respectively (P trend <.001, from 2002 to 2015). The
      prevalence of active HCV in 2002, 2009, 2015, and 2016 was 54.0%, 34.0%, 22.1%,
      and 11.7%, respectively (P trend <.001). The anti-HCV treatment uptake in 2002,
      2009, 2015, and 2016 was 23.0%, 48.0%, 59.3%, and 74.7%, respectively (P trend
      <.001). In 2016, HCV-related cirrhosis was present in 7.6% of all HIV-infected
      individuals, 15.0% of patients with active HCV, and 31.5% of patients who cleared
      HCV after anti-HCV therapy. Conclusions: Our findings suggest that with universal
      access to DAA-based therapy and continued efforts in prevention and screening, it
      will be possible to eliminate active HCV among HIV-infected individuals in Spain
      in the short term. However, the burden of HCV-related cirrhosis will continue to
      be significant among HIV-infected individuals.

PMID- 29354660
TI  - The Effect of Shorter Treatment Regimens for Hepatitis C on Population Health and
      Under Fixed Budgets.
AB  - Background: Direct acting antiviral hepatitis C virus (HCV) therapies are highly
      effective but costly. Wider adoption of an 8-week ledipasvir/sofosbuvir treatment
      regimen could result in significant savings, but may be less efficacious compared
      with a 12-week regimen. We evaluated outcomes under a constrained budget and cost
      effectiveness of 8 vs 12 weeks of therapy in treatment-naive, noncirrhotic,
      genotype 1 HCV-infected black and nonblack individuals and considered scenarios
      of IL28B and NS5A resistance testing to determine treatment duration in
      sensitivity analyses. Methods: We developed a decision tree to use in conjunction
      with Monte Carlo simulation to investigate the cost-effectiveness of recommended
      treatment durations and the population health effect of these strategies given a
      constrained budget. Outcomes included the total number of individuals treated and
      attaining sustained virologic response (SVR) given a constrained budget and
      incremental cost-effectiveness ratios. Results: We found that treating eligible
      (treatment-naive, noncirrhotic, HCV-RNA <6 million copies) individuals with 8
      weeks rather than 12 weeks of therapy was cost-effective and allowed for 50% more
      individuals to attain SVR given a constrained budget among both black and
      nonblack individuals, and our results suggested that NS5A resistance testing is
      cost-effective. Conclusions: Eight-week therapy provides good value, and wider
      adoption of shorter treatment could allow more individuals to attain SVR on the
      population level given a constrained budget. This analysis provides an evidence
      base to justify movement of the 8-week regimen to the preferred regimen list for
      appropriate patients in the HCV treatment guidelines and suggests expanding that
      recommendation to black patients in settings where cost and relapse trade-offs
      are considered.

PMID- 29354659
TI  - Chikungunya Outbreak in Kedougou, Southeastern Senegal in 2009-2010.
AB  - Background: In Senegal, Chikungunya virus (CHIKV), which is an emerging mosquito
      borne alphavirus, circulates in a sylvatic and urban/domestic cycle and has
      caused sporadic human cases and epidemics since 1960s. However, the real impact
      of the CHIKV sylvatic cycle in humans and mechanisms underlying its emergence
      still remains unknown. Methodology: One thousand four hundred nine suspect cases
      of CHIKV infection, recruited from 5 health facilities located in Kedougou
      region, south-eastern Senegal, between May 2009 to March 2010, together with 866
      serum samples collected from schoolchildren from 4 elementary schools in May and
      November 2009 from Kedougou were screened for anti-CHIKV immunoglobulin (Ig)M
      antibodies and, when appropriate, for viral nucleic acid by real-time polymerase
      chain reaction (rPCR) and virus isolation. In addition, mosquitoes collected in
      the same area from May 2009 to January 2010 were tested for CHIKV by rPCR and by
      virus isolation, and 116 monkeys sera collected from March 2010 to May 2010 were
      tested for anti-CHIKV IgM and neutralizing antibodies. Results: The main clinical
      manifestations of the CHIKV suspect cases were headache, myalgia, and arthralgia.
      Evidence for CHIKV infection was observed in 1.4% (20 of 1409) of patients among
      suspect cases. No significant difference was observed among age or sex groups. In
      addition, 25 (2.9%) students had evidence of CHIKV infection in November 2009.
      Chikungunya virus was detected in 42 pools of mosquitoes, mainly from Aedes
      furcifer, and 83% of monkeys sampled were seropositive. Conclusions: Our findings
      further documented that CHIKV is maintained in a sylvatic transmission cycle
      among monkeys and Aedes mosquitoes in Kedougou, and humans become infected by
      exposure to the virus in the forest.

PMID- 29354662
TI  - Severe Rhabdomyolysis Associated With RSV.
AB  - Severe rhabdomyolysis is associated with morbidity and mortality. We report on a
      previously well male who developed severe rhabdomyolysis, sepsis, and multi-organ
      failure. The patient made a complete recovery. Extensive microbiological testing
      was only positive for RSV, making this the first reported case of adult RSV
      related rhabdomyolysis in the literature.

PMID- 29354661
TI  - Decay of HIV DNA in the Reservoir and the Impact of Short Treatment Interruption
      in Kenyan Infants.
AB  - We compared change in HIV reservoir DNA following continued antiretroviral
      therapy (ART) vs short treatment interruption (TI) in early ART-treated Kenyan
      infants. While HIV DNA in the reservoir decayed with continued ART, HIV DNA
      levels were similar to pre-TI HIV DNA reservoir levels in most children after
      short TI.

PMID- 29354663
TI  - Treatment Process and Participant Characteristic Predictors of Substance Use
      Outcome in Mentorship for Addiction Problems (MAP).
AB  - There are a variety of self-help treatments which have components of sponsorship
      or peer support. Although there has been a recent surge in the utilization of
      peer support interventions within clinical settings, there is limited data on
      substance use outcome predictors for interventions designed solely for peer
      support within community treatment settings that are empirically based. We
      examined both treatment process and participant characteristic variables as
      predictors of substance use outcomes within our Stage I pilot which developed a
      new intervention, Mentorship for Addiction Problems (MAP). We found treatment
      process variables to be significantly associated with substance use outcome and
      no participant characteristic variables.

PMID- 29354665
TI  - Hot Carrier Generation and Extraction of Plasmonic Alloy Nanoparticles.
AB  - The conversion of light to electrical and chemical energy has the potential to
      provide meaningful advances to many aspects of daily life, including the
      production of energy, water purification, and optical sensing. Recently,
      plasmonic nanoparticles (PNPs) have been increasingly used in artificial
      photosynthesis (e.g., water splitting) devices in order to extend the visible
      light utilization of semiconductors to light energies below their band gap. These
      nanoparticles absorb light and produce hot electrons and holes that can drive
      artificial photosynthesis reactions. For n-type semiconductor photoanodes
      decorated with PNPs, hot charge carriers are separated by a process called hot
      electron injection (HEI), where hot electrons with sufficient energy are
      transferred to the conduction band of the semiconductor. An important parameter
      that affects the HEI efficiency is the nanoparticle composition, since the hot
      electron energy is sensitive to the electronic band structure of the metal. Alloy
      PNPs are of particular importance for semiconductor/PNPs composites, because by
      changing the alloy composition their absorption spectra can be tuned to
      accurately extend the light absorption of the semiconductor. This work
      experimentally compares the HEI efficiency from Ag, Au, and Ag/Au alloy
      nanoparticles to TiO2 photoanodes for the photoproduction of hydrogen. Alloy PNPs
      not only exhibit tunable absorption but can also improve the stability and
      electronic and catalytic properties of the pure metal PNPs. In this work, we find
      that the Ag/Au alloy PNPs extend the stability of Ag in water to larger applied
      potentials while, at the same time, increasing the interband threshold energy of
      Au. This increasing of the interband energy of Au suppresses the visible-light
      induced interband excitations, favoring intraband excitations that result in
      higher hot electron energies and HEI efficiencies.

PMID- 29354666
TI  - From heart beats to health recipes: The role of fractal physiology in the
      Ancestral Health movement.
AB  - The human body-an amazing biological system that scales up fractally from its
      cellular building blocks-exhibits an incredible ability to self heal. Why then,
      are chronic diseases and degeneration on the rise in the population? Why are we
      sicker, more obese, and more depressed and stressed than ever before in human
      history? Why can't we heal? The answers to these questions may lie in our
      ancestry, and modern departure from the human ecological niche. The ability to
      heal requires proper spatio-temporal inputs-nutrition, sleep, stress, activity,
      and socialization-in order for cellular signaling to occur properly across semi
      permeable cell membranes. We first review key steps in the evolutionary history
      of multicellular life, focusing on the fundamental role of cell-cell
      interactions. Next, we present this as an important framework by which to
      understand how the entrainment of physiological signals in homeostatic mechanisms
      reveals new insights into the processes of disease. Examples are drawn from the
      evolution of metabolism, nutrition, and respiration in multicellular life. We
      argue that disease processes result from a mismatch between the physiological
      inputs an individual receives and their optimal amount and fractal distribution
      as determined by an individual's ancestry. A comparative analysis is a useful
      tool by which to illuminate deep homologies that reveal a mechanistic account for
      disease processes. This cell-molecular approach provides a useful contrast to the
      traditional reductionist approach to disease exemplified by the human genome
      project. As an example, we describe how cell-cell communication drives the
      ontogeny and phylogeny of physiology, producing the tissues, organs, and organ
      systems that hierarchically serve human physiology on various levels. Modern
      society, with its disconnected and stress-riddled lifestyle, is increasingly
      failing to provide the proper inputs for healthy gene expression and
      physiological function. Thus, the answers to our modern health woes-physical,
      mental, and social-may lie in acknowledging the powerful roles that our past has
      played in shaping our bodies. Finding ways to provide the proper inputs of the
      human ecological niche in the modern day may lead to significant, perhaps
      staggering improvements in our health and wellness. The fractal mathematics
      underpinning these dynamics also serves as a metaphor for the Ancestral Health
      Movement, which is currently arising as a multi-cultural, multi-national grass
      roots pluralistic phenomenon.

PMID- 29354664
TI  - Single-Photon Nanoantennas.
AB  - Single-photon nanoantennas are broadband strongly scattering nanostructures
      placed in the near field of a single quantum emitter, with the goal to enhance
      the coupling between the emitter and far-field radiation channels. Recently,
      great strides have been made in the use of nanoantennas to realize fluorescence
      brightness enhancements, and Purcell enhancements, of several orders of
      magnitude. This perspective reviews the key figures of merit by which single
      photon nanoantenna performance is quantified and the recent advances in measuring
      these metrics unambiguously. Next, this perspective discusses what the state of
      the art is in terms of fluoresent brightness enhancements, Purcell factors, and
      directivity control on the level of single photons. Finally, I discuss future
      challenges for single-photon nanoantennas.

PMID- 29354667
TI  - Platelet-activating factor receptor affects food intake and body weight.
AB  - "Let's Move!" is a comprehensive initiative, launched by the First Lady, Michelle
      Obama, dedicates to solving problems of obesity, which is growing in child. The
      life behaviors do affect obesity; however, the mechanistic insight in molecular
      level is still not clear. In this study, by continually monitoring mouse body
      weight under chow and high fat western diets as well as metabolic, physical
      activity and food intake behaviors assessed in a CLAMS Comprehensive Lab Animal
      Monitoring System, we demonstrated that the platelet-activating factor receptor
      (PTAFR) contributes to modification of life behaviors. PTAFR does not affect
      metabolism of ingested dietary fat and carbohydrate in young animals; however,
      Ptafr ablation dramatically increased weight gain without affecting adipose
      tissue accumulation. Ptafr-/- mice possess new habits that increased food intake
      and decreased movement. Our studies suggest that regulation of PTAFR activity may
      be a novel strategy to control obesity in children or young adults.

PMID- 29354669
TI  - Sorting Out the Mechanisms of Benefit of High Flow Nasal Cannula in Stable COPD.

PMID- 29354668
TI  - A spatially explicit approach to the study of socio-demographic inequality in the
      spatial distribution of trees across Boston neighborhoods.
AB  - The racial/ethnic and income composition of neighborhoods often influences local
      amenities, including the potential spatial distribution of trees, which are
      important for population health and community wellbeing, particularly in urban
      areas. This ecological study used spatial analytical methods to assess the
      relationship between neighborhood socio-demographic characteristics (i.e.
      minority racial/ethnic composition and poverty) and tree density at the census
      tact level in Boston, Massachusetts (US). We examined spatial autocorrelation
      with the Global Moran's I for all study variables and in the ordinary least
      squares (OLS) regression residuals as well as computed Spearman correlations non
      adjusted and adjusted for spatial autocorrelation between socio-demographic
      characteristics and tree density. Next, we fit traditional regressions (i.e. OLS
      regression models) and spatial regressions (i.e. spatial simultaneous
      autoregressive models), as appropriate. We found significant positive spatial
      autocorrelation for all neighborhood socio-demographic characteristics (Global
      Moran's I range from 0.24 to 0.86, all P=0.001), for tree density (Global Moran's
      I=0.452, P=0.001), and in the OLS regression residuals (Global Moran's I range
      from 0.32 to 0.38, all P<0.001). Therefore, we fit the spatial simultaneous
      autoregressive models. There was a negative correlation between neighborhood
      percent non-Hispanic Black and tree density (rS=-0.19; conventional P
      value=0.016; spatially adjusted P-value=0.299) as well as a negative correlation
      between predominantly non-Hispanic Black (over 60% Black) neighborhoods and tree
      density (rS=-0.18; conventional P-value=0.019; spatially adjusted P-value=0.180).
      While the conventional OLS regression model found a marginally significant
      inverse relationship between Black neighborhoods and tree density, we found no
      statistically significant relationship between neighborhood socio-demographic
      composition and tree density in the spatial regression models. Methodologically,
      our study suggests the need to take into account spatial autocorrelation as
      findings/conclusions can change when the spatial autocorrelation is ignored.
      Substantively, our findings suggest no need for policy intervention vis-a-vis
      trees in Boston, though we hasten to add that replication studies, and more
      nuanced data on tree quality, age and diversity are needed.

PMID- 29354670
TI  - Effect of Roflumilast on Airway Blood Flow in COPD: A Pilot Study.

PMID- 29354671
TI  - Recruiting Patients After Hospital Discharge for Acute Exacerbation of COPD:
      Challenges and Lessons Learned.
AB  - Background: Hospitalizations for acute exacerbations of chronic obstructive
      pulmonary disease (AECOPD) are associated with increased mortality and decreased
      quality of life. Replicate hospital discharge studies were initiated to examine
      efficacy and safety of once-daily tiotropium HandiHaler(r) versus placebo, in
      addition to usual care, in patients discharged from the hospital after an AECOPD.
      Methods: Both studies were randomized, placebo-controlled, double-blind, parallel
      group, multicenter, with inclusion/exclusion criteria providing a diverse COPD
      patient cohort hospitalized for <=14 days with AECOPD. Patients received
      tiotropium or placebo, initiated within 10 days post-discharge. Target
      recruitment was 604 patients/study and planned duration was event-driven, ending
      after 631 clinical outcome events across both studies. Inability to reach
      targeted site numbers and patient recruitment/retention difficulties led to early
      study termination. Recruitment/retention challenges and protocol amendment
      impacts were assessed qualitatively to understand the major issues. Results: Over
      18 months, 219 patients were enrolled; 158 were randomized and 61 failed
      screening. Premature treatment discontinuation occurred in 49(31%) patients, of
      whom 20(41%) completed health status follow-up. All-cause, 30-day hospital
      readmission was low (8[5%] patients). A total of 154(98%) patients had a
      concomitant diagnosis and most took pulmonary medication pre-randomization
      (143[91%]) and during study treatment (144[92%]). Inclusion/exclusion criteria
      changes failed to improve recruitment. Recruitment/retention barriers were
      identified, relating to patient and clinician factors, health care
      infrastructure, and clinical practices. Conclusions: Although AECOPD
      hospitalization is clinically important and incurs high costs, significant
      challenges exist in studying this population in clinical trials after
      hospitalization. Studies are needed to evaluate effective management of AECOPD
      patients at high risk of adverse clinical outcomes.

PMID- 29354672
TI  - Impact of Heated Humidified High Flow Air via Nasal Cannula on Respiratory Effort
      in Patients with Chronic Obstructive Pulmonary Disease.
AB  - Background: High flow nasal cannula therapy (HFNC) has been widely adopted for
      respiratory distress, and evidence suggests that purging dead space of the upper
      airway improves gas fractions in the lung. This study tests the hypothesis that
      HFNC with room air could be as effective as low flow oxygen in chronic
      obstructive pulmonary disease (COPD). Methods: Thirty-two COPD patients
      prescribed 1 - 2 L/min of oxygen were studied. The conditions tested consisted of
      a control (CTRL; no therapy), then in random order HFNC and prescribed low flow
      oxygen (LFO). HFNC was the highest flow tolerated up to 35 L/min without
      supplemental oxygen. Arterial blood gases (ABGs), respiratory rate (RR), heart
      rate (HR) and tidal volume (VT) were measured at the end of each condition.
      Results: Arterial oxygen (PaO2) was greater (p < 0.001) for LFO than both HFNC
      and CTRL (CTRL=57.4+/-6.1mmHg, HFNC=58.6+/-8.3mmHg, LFO=72.6+/-10.2mmHg). HFNC
      reduced RR by 11% (p<0.05) from CTRL and LFO (CTRL=20.2+/-3.8br/min, HFNC=17.9+/
      3.3br/min, LFO=20.2+/-3.7br/min) with no differences in VT. There were no
      differences between arterial carbon dioxide (PaCO2) (CTRL=45.5+/-4.9mmHg,
      HFNC=45.0+/-5.3mmHg, LFO=46.0+/-3.9mmHg). Conclusions: HFNC resulted in a
      clinically relevant reduction in ventilatory effort with no change in ABG
      indicating a gas equilibrium effect of purging anatomical dead space. Clinical
      Trial Registration: ClinicalTrials.gov ID: NCT00990210.

PMID- 29354673
TI  - Evaluation and Documentation of Supplemental Oxygen Requirements is Rarely
      Performed in Patients Hospitalized With COPD.
AB  - Rationale: Patients hospitalized with chronic obstructive pulmonary disease
      (COPD) who require supplemental oxygen (O2) are at increased risk of hospital
      readmissions. There is a paucity of information regarding quality of evaluation
      and documentation regarding the need for supplemental O2 in this population. 
      Objective: To determine the extent to which evaluation and documentation
      regarding the need for supplemental O2 occurs prior to hospital discharge in
      patients with COPD.  Methods: We conducted a two-center retrospective cohort
      study of hospitalized adults with a physician diagnosis of COPD.  We reviewed
      electronic health records to ascertain whether patients underwent evaluation
      beyond rest oximetry documenting hypoxemia and if there was adequate
      documentation of supplemental O2 requirements prior to discharge. Results:  Of
      526 patients hospitalized with a primary or secondary discharge diagnosis of
      COPD, 335 patients (mean age 69 years, 78% with diagnosis of COPD exacerbation)
      met eligibility criteria. Overall, 1 in 5 (22%, 73/335) hospitalized patients
      with COPD had an evaluation beyond rest oximetry for supplemental O2 requirements
      during admission.  Adequate documentation of supplemental O2 requirements
      occurred in even fewer patients (16%, 54/335). Both evaluation (26% versus 5%,
      p=0.002) and documentation (19% versus 4%, p=0.001) of supplemental O2
      requirements were more common in patients hospitalized for a COPD exacerbation
      compared to those hospitalized with COPD but without an exacerbation.
      Conclusions: Evaluation and documentation of supplemental O2 requirements beyond
      rest oximetry occur infrequently in patients hospitalized with COPD.

PMID- 29354675
TI  - Abstract Presentations: COPD10usa 2017.

PMID- 29354674
TI  - Differences in Respiratory Symptoms and Lung Structure Between Hispanic and Non
      Hispanic White Smokers: A Comparative Study.
AB  - Background: Prior studies have demonstrated that U.S. Hispanic smokers have a
      lower risk of decline in lung function and chronic obstructive pulmonary disease
      (COPD) compared with non-Hispanic whites (NHW). This suggests there might be
      racial-ethnic differences in susceptibility in cigarette smoke-induced
      respiratory symptoms, lung parenchymal destruction, and airway and vascular
      disease, as well as in extra-pulmonary manifestations of COPD. Therefore, we
      aimed to explore respiratory symptoms, lung function, and pulmonary and extra
      pulmonary structural changes in Hispanic and NHW smokers. Methods: We compared
      respiratory symptoms, lung function, and computed tomography (CT) measures of
      emphysema-like tissue, airway disease, the branching generation number (BGN) to
      reach a 2-mm-lumen-diameter airway, and vascular pruning as well as muscle and
      fat mass between 39 Hispanic and 39 sex-, age- and smoking exposure-matched NHW
      smokers. Results: Hispanic smokers had higher odds of dyspnea than NHW after
      adjustment for COPD and asthma statuses (odds ratio[OR] = 2.96; 95% confidence
      interval [CI] 1.09-8.04), but no significant differences were found in lung
      function and CT measurements. Conclusions: While lung function and CT measures of
      the lung structure were similar, dyspnea is reported more frequently by Hispanic
      than matched-NHW smokers. It seems to be an impossible puzzle but it's easy to
      solve a Rubik' Cube using a few algorithms.

PMID- 29354676
TI  - The COPD Pipeline XXXVI.

PMID- 29354677
TI  - The Journal Club: Computed Tomography and COPD.

PMID- 29354678
TI  - Up-Down-Like Background Spiking Can Enhance Neural Information Transmission.
AB  - How neurons transmit information about sensory or internal signals is strongly
      influenced by ongoing internal activity. Depending on brain state, this
      background spiking can occur asynchronously or clustered in up states, periods of
      collective firing that are interspersed by silent down states. Here, we study
      which effect such up-down (UD) transitions have on signal transmission. In a
      simple model, we obtain numerical and analytical results for information
      theoretic measures. We find that, surprisingly, an UD background can benefit
      information transmission: when background activity is sparse, it is advantageous
      to distribute spikes into up states rather than uniformly in time. We reproduce
      the same effect in a more realistic recurrent network and show that signal
      transmission is further improved by incorporating that up states propagate across
      cortex as traveling waves. We propose that traveling UD activity might represent
      a compromise between reducing metabolic strain and maintaining information
      transmission capabilities.

PMID- 29354679
TI  - Cortical Merging in S1 as a Substrate for Tactile Input Grouping.
AB  - Perception is a reconstruction process guided by rules based on knowledge about
      the world. Little is known about the neural implementation of the rules of object
      formation in the tactile sensory system. When two close tactile stimuli are
      delivered simultaneously on the skin, subjects feel a unique sensation, spatially
      centered between the two stimuli. Voltage-sensitive dye imaging (VSDi) and
      electrophysiological recordings [local field potentials (LFPs) and single units]
      were used to extract the cortical representation of two-point tactile stimuli in
      the primary somatosensory cortex of anesthetized Long-Evans rats. Although layer
      4 LFP responses to brief costimulation of the distal region of two digits
      resembled the sum of individual responses, approximately one-third of single
      units demonstrated merging-compatible changes. In contrast to previous intrinsic
      optical imaging studies, VSD activations reflecting layer 2/3 activity were
      centered between the representations of the digits stimulated alone. This merging
      was found for every tested distance between the stimulated digits. We discuss
      this laminar difference as evidence that merging occurs through a buildup stream
      and depends on the superposition of inputs, which increases with successive
      stages of sensory processing. These findings show that layers 2/3 are involved in
      the grouping of sensory inputs. This process that could be inscribed in the
      cortical computing routine and network organization is likely to promote object
      formation and implement perception rules.

PMID- 29354681
TI  - Lingual Gyrus Surface Area Is Associated with Anxiety-Depression Severity in
      Young Adults: A Genetic Clustering Approach.
AB  - Here we aimed to identify cortical endophenotypes for anxiety-depression. Our
      data-driven approach used vertex-wise genetic correlations (estimated from a twin
      sample: 157 monozygotic and 194 dizygotic twin pairs) to parcellate cortical
      thickness (CT) and surface area (SA) into genetically homogeneous regions (Chen
      et al., 2013). In an overlapping twin and sibling sample (n = 834; aged 15-29,
      66% female), in those with anxiety-depression Somatic and Psychological Health
      Report (SPHERE) scores (Hickie et al., 2001) above median, we found a reduction
      of SA in an occipito-temporal cluster, which comprised part of the right lingual,
      fusiform and parahippocampal gyrii. A similar reduction was observed in the Human
      Connectome Project (HCP) sample (n = 890, age 22-37, 56.5% female) in those with
      Adult Self Report (ASR) DSM-oriented scores (Achenbach et al., 2005) in the 25
      95% quantiles. A post hoc vertex-wise analysis identified the right lingual and,
      to a lesser extent the fusiform gyrus. Overall, the surface reduction explained
      by the anxiety-depression scores was modest (r = -0.10, 3rd order spline, and r =
      -0.040, 1st order spline in the HCP). The discordant results in the top 5% of the
      anxiety-depression scores may be explained by differences in recruitment between
      the studies. However, we could not conclude whether this cortical region was an
      endophenotype for anxiety-depression as the genetic correlations did not reach
      significance, which we attribute to the modest effect size (post hoc statistical
      power <10%).

PMID- 29354680
TI  - Differential Rates of Perinatal Maturation of Human Primary and Nonprimary
      Auditory Cortex.
AB  - Primary and nonprimary cerebral cortex mature along different timescales;
      however, the differences between the rates of maturation of primary and
      nonprimary cortex are unclear. Cortical maturation can be measured through
      changes in tissue microstructure detectable by diffusion magnetic resonance
      imaging (MRI). In this study, diffusion tensor imaging (DTI) was used to
      characterize the maturation of Heschl's gyrus (HG), which contains both primary
      auditory cortex (pAC) and nonprimary auditory cortex (nAC), in 90 preterm infants
      between 26 and 42 weeks postmenstrual age (PMA). The preterm infants were in
      different acoustical environments during their hospitalization: 46 in open ward
      beds and 44 in single rooms. A control group consisted of 15 term-born infants.
      Diffusion parameters revealed that (1) changes in cortical microstructure that
      accompany cortical maturation had largely already occurred in pAC by 28 weeks
      PMA, and (2) rapid changes were taking place in nAC between 26 and 42 weeks PMA.
      At term equivalent PMA, diffusion parameters for auditory cortex were different
      between preterm infants and term control infants, reflecting either delayed
      maturation or injury. No effect of room type was observed. For the preterm group,
      disturbed maturation of nonprimary (but not primary) auditory cortex was
      associated with poorer language performance at age two years.

PMID- 29354682
TI  - Neural Correlates of Temporal Complexity and Synchrony during Audiovisual
      Correspondence Detection.
AB  - We often perceive real-life objects as multisensory cues through space and time.
      A key challenge for audiovisual integration is to match neural signals that not
      only originate from different sensory modalities but also that typically reach
      the observer at slightly different times. In humans, complex, unpredictable
      audiovisual streams lead to higher levels of perceptual coherence than
      predictable, rhythmic streams. In addition, perceptual coherence for complex
      signals seems less affected by increased asynchrony between visual and auditory
      modalities than for simple signals. Here, we used functional magnetic resonance
      imaging to determine the human neural correlates of audiovisual signals with
      different levels of temporal complexity and synchrony. Our study demonstrated
      that greater perceptual asynchrony and lower signal complexity impaired
      performance in an audiovisual coherence-matching task. Differences in asynchrony
      and complexity were also underpinned by a partially different set of brain
      regions. In particular, our results suggest that, while regions in the
      dorsolateral prefrontal cortex (DLPFC) were modulated by differences in memory
      load due to stimulus asynchrony, areas traditionally thought to be involved in
      speech production and recognition, such as the inferior frontal and superior
      temporal cortex, were modulated by the temporal complexity of the audiovisual
      signals. Our results, therefore, indicate specific processing roles for different
      subregions of the fronto-temporal cortex during audiovisual coherence detection.

PMID- 29354683
TI  - The use of accelerometry as a tool to measure disturbed nocturnal sleep in
      Parkinson's disease.
AB  - Sleep disturbances are common in Parkinson's disease (PD). We used the
      Parkinson's KinetiGraph (PKG), an objective movement recording system for PD to
      assess night time sleep in 155 people aged over 60 and without PD (controls), 72
      people with PD (PwP) and 46 subjects undergoing a Polysomnogram (PSG: 36 with
      sleep disorder and 10 with normal sleep). The PKG system uses a wrist worn logger
      to capture acceleration and derive a bradykinesia score (BKS) every 2 min over 6
      days. The BKS ranges from 0-160 with higher scores associated with lesser
      mobility. Previously we showed that BKS > 80 were associated with day time sleep
      and used this to produce scores for night time sleep: Efficiency (Percent time
      with BKS > 80), Fragmentation (Average duration of runs of BKS > 80) and Sleep
      Quality (BKS > 111 as a representation of atonia). There was a fair association
      with BKS score and sleep level as judged by PSG. Using these PKG scores, it was
      possible to distinguish between normal and abnormal PSG studies with good
      Selectivity (86%) and Sensitivity (80%). The PKG's sleep scores were
      significantly different in PD and Controls and correlated with a subject's self
      assessment (PDSS 2) of the quality, wakefulness and restlessness. Using both the
      PDSS 2 and the PKG, it was apparent that sleep disturbances were apparent early
      in disease in many PD subjects and that subjects with poor night time sleep were
      more likely to have day time sleepiness. This system shows promise as a
      quantitative score for assessing sleep in Parkinson's disease.

PMID- 29354685
TI  - Inflammatory gene expression signatures in idiopathic intracranial hypertension:
      possible implications in microgravity-induced ICP elevation.
AB  - The visual impairment and intracranial pressure (VIIP) syndrome is a neuro
      ophthalmologic condition described in astronauts returning from long duration
      space missions. Idiopathic intracranial hypertension (IIH), also known as
      pseudotumor cerebri, is characterized by a chronic elevation of intracranial
      pressure (ICP) in the absence of an intracranial mass lesion. Because VIIP and
      IIH share some neurologic and ophthalmologic manifestations, the latter might be
      used as a model to study some of the processes underlying VIIP. This work
      constitutes a preliminary investigation of the molecular pathways associated with
      the elevation of ICP in IIH. Gene expression signatures were obtained from
      exosomes collected from CSF and plasma in patients with possible signs of IIH.
      The gene expression targets focused on inflammatory genes and miRNAs. The results
      suggest that inflammatory cytokine-driven processes and immune cell migration are
      activated when ICP is elevated in IIH patients, either as a cause or effect of
      the ICP increase. Several miRNAs appear to be involved in this response, among
      which miR-9 and miR-16 are upregulated in CSF and plasma of higher ICP subjects.
      This study provides evidence in support of neurophysiological alterations and
      neuro-immunomodulation in this condition. If similar changes are seen in
      astronauts manifesting with the VIIP syndrome, an underlying pathophysiological
      basis may be discovered.

PMID- 29354684
TI  - Optimizing olfactory testing for the diagnosis of Parkinson's disease: item
      analysis of the university of Pennsylvania smell identification test.
AB  - The 40-item University of Pennsylvania Smell Identification Test (UPSIT) is an
      effective instrument to detect olfactory dusfunction in Parkinson's disease (PD).
      It is not clear, however, whether tests of this length are necessary to detect
      such dysfunction. Several studies have suggested that detection of certain odors
      is selectively compromised in PD, and that a test comprised of these odors could
      be shorter and more specific for this purpose. Therefore, we attempted to
      identify a subset of UPSIT odors that distinguish PD from controls with similar
      or improved test characteristics compared to the full test. The discriminatory
      power of each odor was examined using UPSIT data from a discovery cohort of 314
      PD patients and 314 matched controls and ranked using multiple methods (including
      odds ratios, regression coefficients and discriminant analysis). To validate
      optimally discriminant subsets, we calculated test characteristics using data
      from two independent cohorts (totaling 306 PD and 343 controls). In the discovery
      cohort, multiple novel 12-item subsets (and the previously described Brief Smell
      Identification Test-B) performed similarly or improved upon the UPSIT and were
      better than 12 random items. However, in validation studies from independent
      cohorts, multiple subsets retained test characteristics similar to the full
      UPSIT, but did not outperform 12 random items. Differential discriminatory power
      of individual items is not conserved across independent cohorts arguing against
      selective hyposmia in PD. However, multiple 12-item subsets performed as well as
      the full UPSIT. These subsets could form the basis for shorter olfactory tests in
      the clinical evaluation of Parkinsonism.

PMID- 29354686
TI  - E2112: randomized phase iii trial of endocrine therapy plus entinostat/placebo in
      patients with hormone receptor-positive advanced breast cancer.
AB  - Endocrine therapies are effective in the treatment of hormone receptor (HR)
      positive breast cancer, however, de novo or acquired treatment resistance is a
      significant clinical problem. A potential mechanism of resistance involves
      changes in gene expression secondary to epigenetic modifications, which might be
      reversed with the use of histone deacetylase (HDAC) inhibitors such as
      entinostat. The ENCORE 301 phase II randomized, placebo-controlled study
      demonstrated a significant improvement in progression-free survival (PFS) and
      overall survival (OS), with the addition of entinostat to exemestane in patients
      with HR-positive advanced breast cancer with disease progression after prior non
      steroidal aromatase inhibitor (AI). These results prompted the development of
      E2112, a phase III registration trial which is investigating entinostat/placebo
      in combination with exemestane in patients with locally advanced or metastatic
      breast cancer who have experienced disease progression after a non-steroidal AI.
      E2112 aims to validate the preclinical and clinical findings supporting the role
      of HDAC inhibitors in overcoming resistance to endocrine therapy in breast
      cancer, and ultimately improve outcomes for patients with advanced breast cancer.

PMID- 29354687
TI  - Usefulness of the Audience Response System in training lay health advisors for
      chronic disease prevention.
AB  - Lay health promoters (LHPs) have been successful in preventing disease. Given the
      complexity of health interventions, a crucial component that is necessary for
      LHPs' success is the training they receive. Engaging methods have the potential
      to increase LHPs' learning and efficacy to implement health interventions. The
      Audience Response System (ARS) has successfully facilitated interactive learning
      in several settings, but has not been used to train LHPs. This paper describes
      how the ARS was used in LHP training to implement a complex behavioral
      intervention, reports the training results, and serves as a model for others who
      work with LHPs.

PMID- 29354688
TI  - HIPAA Compliant Wireless Sensing Smartwatch Application for the Self-Management
      of Pediatric Asthma.
AB  - Asthma is the most prevalent chronic disease among pediatrics, as it is the
      leading cause of student absenteeism and hospitalization for those under the age
      of 15. To address the significant need to manage this disease in children, the
      authors present a mobile health (mHealth) system that determines the risk of an
      asthma attack through physiological and environmental wireless sensors and
      representational state transfer application program interfaces (RESTful APIs).
      The data is sent from wireless sensors to a smartwatch application (app) via a
      Health Insurance Portability and Accountability Act (HIPAA) compliant
      cryptography framework, which then sends data to a cloud for real-time analytics.
      The asthma risk is then sent to the smartwatch and provided to the user via
      simple graphics for easy interpretation by children. After testing the safety and
      feasibility of the system in an adult with moderate asthma prior to testing in
      children, it was found that the analytics model is able to determine the overall
      asthma risk (high, medium, or low risk) with an accuracy of 80.10+/-14.13%.
      Furthermore, the features most important for assessing the risk of an asthma
      attack were multifaceted, highlighting the importance of continuously monitoring
      different wireless sensors and RESTful APIs. Future testing this asthma attack
      risk prediction system in pediatric asthma individuals may lead to an effective
      self-management asthma program.

PMID- 29354690
TI  - Facilitating a close interaction between basic, translational and clinical
      science: BMJ Open Ophthalmology.

PMID- 29354691
TI  - Effect of chronic alcohol and tobacco use on retinal nerve fibre layer thickness:
      a case-control study.
AB  - Objective: To identify the effects of chronic alcohol and/or tobacco use on
      retinal nerve fibre layer (RNFL) thickness and to find the association between
      severity of addiction with RNFL thinning. Methodology: A case-control study was
      performed in 200 eyes of cases and 200 healthy control eyes. Cases were recruited
      from deaddiction clinic having history of alcohol and/or tobacco use for at least
      5 years. Severity of alcohol and tobacco was graded by Alcohol Use Disorders
      Identification Test (AUDIT) and Fagerstorm Nicotine Dependence (FTND) scale,
      respectively. Age-matched and gender-matched individuals attending ophthalmology
      outpatient department without addiction were recruited as controls. RNFL
      thickness was measured using Stratus optical coherence tomography (OCT). Results:
      Statistically significant RNFL thinning was noted in all quadrants except nasal
      quadrant in the cases. Statistically significant thinning was seen in all
      quadrants except nasal with increased FTND scale. Thinning was noted in all
      quadrants with higher AUDIT scale, but this was statistically not significant.
      Conclusion: Chronic alcohol and tobacco use are likely to cause RNFL thinning.
      OCT can be used as a screening tool to suspect visual morbidities in chronic
      tobacco and alcohol users.

PMID- 29354689
TI  - A systematic review of childhood obesity in the Middle East and North Africa
      (MENA) region: Prevalence and risk factors meta-analysis.
AB  - Obesity rates are rising globally, but there is evidence that young people in the
      Middle East and North Africa (MENA) region are at particularly high risk. We
      systematically searched the literature to map the MENA region for prevalence of
      childhood overweight and obesity, and examine the underlying risk factors and
      adverse effects associated with obesity in this region. Inclusion criteria were:
      English-language, non-basic-science focused articles that used any of the
      standard obesity definitions and were conducted in the MENA countries within the
      last five years. We searched PubMed using combinations of key terms ((childhood)
      OR adolescence) AND obesity) AND (MENA or each country) AND ("last five years"
      [PDat]). Studies demonstrated an increasing prevalence of obesity among many
      countries in the MENA region, especially in the Gulf area. Notably, in Kuwait,
      prevalence rates of overweight and obesity were 25.6% and 34.8% among young males
      and 20.8% and 20.5% among females. A meta-analysis revealed that physical
      inactivity, increased screen time, and higher social status were risk factors for
      childhood obesity. Childhood and adolescent obesity is a major challenge facing
      countries of the MENA region. Further research is needed to fully investigate the
      role of nutrition and other specific risk factors and evaluate various
      interventions to manage this pervasive and growing health problem.

PMID- 29354692
TI  - The Effect of Vitrectomy Infusion Solutions on Postoperative Electroretinography
      and Retina Histology.
AB  - Purpose: A prospective, randomised, masked study comparing three different
      intraocular infusion solutions used during vitrectomy on postoperative
      electroretinography (ERG) and retinal histology of rabbit eyes. Methods materials
      and animals: Twelve rabbit eyes were used with each group of three intraocular
      infusion solutions: Lactated Ringers (LR), balanced salt solution (BSS) and
      balanced salt solution-plus (BSS-Plus). Results: At 24 hours postoperatively, the
      ERG values were 36%, 68% and 75% of the normal values for LR, BSS and BSS-Plus,
      respectively. At 72 hours postoperatively, the ERG values were 50%, 84% and 100%
      of the normal values for LR, BSS and BSS-Plus, respectively. At 72 hours
      postoperatively, 3/12, 10/12 and 12/12 of the vitrectomised eyes had regained
      normal-value ERGs for LR, BSS, and BSS-Plus eyes, respectively. At 1 week
      postoperatively, 4/12 and 12/12 of LR and BSS eyes, respectively, had normal
      ERGs. The number of LR eyes regaining normal ERG values was 4/12, 6/12 and 9/12,
      measured at 1, 4 and 15 weeks postoperatively, respectively. Retina histology: At
      15 weeks follow-up, histopathology was performed on several rabbit eyes.
      Histological examination of LR-irrigated eyes showed 2/7 normal retinas, whereas
      5/7 showed changes that ranged from vacuoles in the inner retina to numerous
      vacuoles in both the outer and inner retina with disruption of the inner nuclear
      layer. The histology of BSS-infused and BSS-Plus-infused rabbit eyes was normal.
      Conclusion: LR solution, when used during vitrectomy, has a more prolonged
      negative effect on ERG than BSS and BSS-Plus. Histological changes seen in LR
      eyes may explain the ERG results.

PMID- 29354693
TI  - Adult bacterial conjunctivitis: resistance patterns over 12 years in patients
      attending a large primary eye care centre in the UK.
AB  - Purpose: To determine whether there was a change in the resistance pattern of
      bacteria isolated from cases of conjunctivitis following the introduction of over
      the-counter availability of chloramphenicol in 2005. Design and setting:
      Retrospective review of laboratory records for adult patients with suspected
      bacterial conjunctivitis between 2001 and 2012 attending the Royal Liverpool
      University Hospital. Participants: Patients with suspected bacterial
      conjunctivitis. Organisms were identified by standard laboratory methods. Scanty
      growth and normal flora were considered as a negative result. For positive
      results, susceptibility testing was undertaken as per British Society for
      Antimicrobial Chemotherapy guidelines. Main outcome measures: Prevalence of
      groups of bacteria associated with acute conjunctivitis and their resistance to
      chloramphenicol, ciprofloxacin, gentamicin, and methicillin. Results: A total of
      8209 conjunctival swabs were reviewed; 1300 (15.8%) were considered positive, of
      which 977 (75.2%) and 323 (24.8%) bacteria were identified as Gram positive and
      Gram negative, respectively. Staphylococcus aureus was the most prevalent
      organism identified. Resistance of all bacterial isolates to chloramphenicol was
      8.4% varying from 3.0% to 16.4% while that for ciprofloxacin and gentamicin was
      16.4% and 14.0%, respectively. Methicillin resistance among S. aureus was 8.3%.
      Conclusion: Resistance to chloramphenicol has remained stable since being made
      available over the counter. Among Gram-positive bacteria, the most prevalent
      causative agent of bacterial conjunctivitis, chloramphenicol sensitivity remains
      high.

PMID- 29354694
TI  - Whole-body positional manipulators for ocular imaging of anaesthetised mice and
      rats: a do-it-yourself guide.
AB  - Background: In vivo retinal imaging of rodents has gained a growing interest in
      ophthalmology and neurology. The bedding of the animals with the possibility to
      perform adjustments in order to obtain an ideal camera-to-eye angle is
      challenging. Methods: We provide a guide for a cost-effective, do-it-yourself
      rodent holder for ocular imaging techniques. The set-up was tested and refined in
      over 2000 optical coherence tomography measurements of mice and rats. Results:
      The recommended material is very affordable, readily available and easily
      assembled. The holder can be adapted to both mice and rats. A custom-made
      mouthpiece is provided for the use of inhalant anaesthesia. The holder is highly
      functional and assures that the rodent's eye is the centre of rotation for
      adjustments in both the axial and the transverse planes with a major time benefit
      over unrestrained positioning of the rodents. Conclusion: We believe this guide
      is very useful for eye researchers focusing on in vivo retinal imaging in rodents
      as it significantly reduces examination times for ocular imaging.

PMID- 29354695
TI  - The impact of anthropometric and ocular parameters on optic cup-to-disc ratio.
AB  - Background/aims: To assess a relationship between vertical cup--to--disc ratio
      (VCDR), which is a useful tool to assist in the diagnosis of glaucoma in the
      early to medium--advanced stages, and intraocular pressure (IOP), central corneal
      thickness (CCT), body mass index (BMI) and body fat percentage (BFP). Methods:
      The data were collected from general populations living in the centre of Japan
      who had participated in the third wave of the National Institute for Longevity
      Sciences - Longitudinal Study of Aging. VCDR was set in the general linear mixed
      model as objective variables with adjustment for age and optic disc area.
      Explanatory variables were IOP, CCT, BMI and BFP. Results: 2819 eyes with no
      surgical history (788 men, 739 women; average age, 59.6+/-11.7 years) were
      included in the multivariate analysis. VCDR significantly increased with a low
      BMI in men (estimated effect=-0.0059, p=0.0426). Meanwhile, VCDR significantly
      increased with a high IOP (estimated effect=0.0125, p<0.0001) and a thin CCT
      (estimated effect=-0.4229, p=0.0425) in women. There was no significant
      relationship of VCDR with IOP, CCT and BFP in men and with BMI and BFP in women.
      Only the relationship between IOP and VCDR in women would be statistically
      significant after applying Bonferroni's correction for multiple comparisons,
      under the assumption that each analysis was not independent. Conclusions: This
      study demonstrated the different association with VCDR and other factors by sex.
      A low BMI in men and a high IOP and a thin CCT in women were indicated to be a
      risk factor of a greater VCDR. Meanwhile BFP was not a significant factor of a
      greater VCDR in both sexes.

PMID- 29354697
TI  - Awareness and knowledge about glaucoma and proportion of people with glaucoma in
      an urban outreach programme in Southeast Nigeria.
AB  - Aim: The aim of this study was to determine the level of awareness and knowledge
      of glaucoma and the proportion of people with glaucoma among participants of a 1
      day urban eye outreach programme. Methods: The study was a cross-sectional
      survey. Data, collected by means of a structured questionnaire, included
      participants' demographic details, and awareness, knowledge and ocular status as
      regards glaucoma. Publicity for the outreach was created through the mass media
      (radio stations and television), churches, handbills, posters and different
      hospital staff. Data analysis was by Statistical Package for Social
      SciencesV.20.0. Associations between participants' demographic and other details
      were tested using Pearson's chi2 test, and a p value of <0.05 was considered
      significant. Results: Four hundred and seventy-eight (93.2%) of the 513 people in
      attendance were eligible and consented to participate. Awareness, knowledge and
      proportion of people with glaucoma in the study population were 65.5%, 36.8% and
      14.5%, respectively. Awareness was significantly associated with attainment of
      some formal education, awareness of a positive family history, and having had an
      eye check prior to the outreach. The mass media was the most common information
      source. Good knowledge level was significantly associated with higher educational
      attainment and occupation, whereas proportion of people with glaucoma was
      significantly associated with increasing age. Conclusion: Improving awareness
      with suitable content for the target population through effective means such as
      the mass media may be a veritable first step in combating blindness from
      glaucoma.

PMID- 29354696
TI  - The prevalence of visual symptoms in poppers users: a global survey.
AB  - Introduction and aims: The use of 'poppers' (volatile alkyl nitrites) has been
      associated with the development of visual symptoms secondary to the development
      of maculopathy. There are currently no data regarding the prevalence of this
      condition among poppers users. The aim of this study was to quantify the presence
      of visual symptoms among poppers users from a global cohort. Design and methods:
      The Global Drug Survey (GDS) conducts annual anonymous online surveys of drug and
      alcohol use. Within the 2012 GDS, questions were inserted regarding the presence
      of visual symptoms in poppers users. Results: The GDS received a total of 21 575
      valid responses, with a total of 17 479 from the UK, Australia, USA and Eurozone.
      Within these areas, 5152 (29.5%) had used poppers within their lifetime and 1322
      (7.6%) within the previous year. Of the 'last year' users, when asked the
      question: 'Do you think poppers use has affected your eyesight?', 29 (2.2%)
      people responded 'yes', 130 (10.0%) responded 'maybe' and 1146 (87.8%) responded
      'no (17 people did not answer). Both multiple choice and free-text responses
      regarding the nature of visual symptoms correlated with the central visual
      disturbance that would be expected from maculopathy. There was significant
      increased symptom prevalence with age (likelihood ratio (chi2)=19.0; p<0.001).
      Discussion and conclusions: This study demonstrates that a small, yet significant
      from a public health perspective, proportion of poppers users have visual
      symptoms. Clinical correlation is required to determine whether these reported
      symptoms are due to poppers associated maculopathy, or an alternative cause.

PMID- 29354698
TI  - Disposable versus non-disposable tonometer prisms: a UK national survey.
AB  - Purpose: To determine the prevalence of disposable tonometer versus non
      disposable tonometer use in the UK and to determine methods of decontamination
      and frequency of replacement of prisms.A total of 137 ophthalmology departments
      were interviewed by telephone using a structured questionnaire. The main outcome
      measured were:types of tonometer prisms used in clinic (disposable, non
      disposable and/or other)average disposable prisms used per clinic sessionaverage
      lifespan of non-disposable prismsprism preference by glaucoma and other teams
      within department.A cost and benefit analysis was then performed on the data
      acquired. Results: One hundred and fifty-five departments were identified for the
      survey. Of these, 137 (88.3%) responded. Eighty-one departments (59.1%) used
      Tonosafe prisms alone, whereas 22 departments (16.1%) used Goldmann non
      disposable prisms exclusively. Thirty-five departments (64%) on average have a
      change rate of 26.5% per year (range: 0-100, median: 20) attributed to damage,
      loss or theft. Sixteen departments (29%) reported that prisms were used until
      damaged or lost. Four departments (7%) were uncertain of their prism usage and
      could not provide further information. Conclusions: Majority of eye departments
      in the UK opt for disposable prisms. This survey shows the perceived cost
      effectiveness of disposable prisms is overestimated when the true cost of
      disinfection and damage is taken into account. Significant cost savings coupled
      with the low risk of infectivity (if decontaminated properly) should prompt
      clinicians and ophthalmic departments worldwide to reconsider the use of non
      disposable prisms.

PMID- 29354700
TI  - Retinal embolic events: frequency and impact following transcatheter aortic valve
      implantation (TAVI) for aortic stenosis.
AB  - Objectives: Transcatheter aortic valve implantation (TAVI) is an established
      treatment for patients with severe symptomatic aortic stenosis. It has a
      cerebrovascular accident rate of about 5% but the effect on retinal embolic
      events has not been previously reported. This study investigated the occurrence
      of retinal emboli following TAVI. Methods and analysis: In this prospective
      observational study, 20 patients underwent full ophthalmic examination to assess
      retinal embolic events prior to TAVI and at 48 hours and 1 month post-TAVI.
      Results: At 48 hours post-TAVI, one patient had a new cotton wool spot in the
      right eye. At 1 month, another two patients had new retinal emboli events in at
      least one eye and a fourth patient developed retinal splinter haemorrhages in the
      right eye. Conclusion: Retinal embolic events and new retinal abnormalities
      following TAVI occurred in 15% and 20% of our cohort, respectively, without any
      associated retinal damage or significant visual problems. Retinal evaluation may
      be a useful surrogate test for cerebral embolisation in future studies assessing
      the utility of new valve prostheses and embolic protection devices.

PMID- 29354699
TI  - Retinal vasculature in glaucoma: a review.
AB  - Despite the critical impact of glaucoma on global blindness, its aetiology is not
      fully characterised. Elevated intraocular pressure is highly associated with
      glaucomatous optic neuropathy. However, visual field loss still progresses in
      some patients with normal or even low intraocular pressure. Vascular factors have
      been suggested to play a role in glaucoma development, based on numerous studies
      showing associations of glaucoma with blood pressure, ocular perfusion pressure,
      vasospasm, cardiovascular disease and ocular blood flow. As the retinal
      vasculature is the only part of the human circulation that readily allows non
      invasive visualisation of the microcirculation, a number of quantitative retinal
      vascular parameters measured from retinal photographs using computer software
      (eg, calibre, fractal dimension, tortuosity and branching angle) are currently
      being explored for any association with glaucoma and its progression. Several
      population-based and clinical studies have reported that changes in retinal
      vasculature (eg, retinal arteriolar narrowing and decreased fractal dimension)
      are associated with optic nerve damage and glaucoma, supporting the vascular
      theory of glaucoma pathogenesis. This review summarises recent findings on the
      relationships between quantitatively measured structural retinal vascular changes
      with glaucoma and other markers of optic nerve head damage, including retinal
      nerve fibre layer thickness. Clinical implications, recent new advances in
      retinal vascular imaging (eg, optical coherence tomography angiography) and
      future research directions are also discussed.

PMID- 29354701
TI  - Reducing oral contamination during corneal scrapes.
AB  - Aims: To identify potential contaminants of the corneal sampling procedure and
      examine the effect of wearing surgical face masks on the rate of contamination.
      Methods: Ten surgeons recited out loud a 30 s standardised script for corneal
      scraping with blood agar plates positioned 30 cm away from them. Three groups
      were identified: in group 1 a surgical mask was worn; group 2 had no mask worn;
      and group 3 had no mask but used agar plates pretreated with 5% povidone-iodine
      as a negative control. Each surgeon repeated the process 10 times for all groups,
      totalling 30 plates per surgeon and 300 plates for the experiment. All plates
      were masked and incubated aerobically at 37 degrees C for 24 hours, and the
      number of colony forming units (CFUs) was determined. Results: At 24 hours, group
      1 had a mean of 0.3 CFUs per surgeon; group 2 had 6.4 CFUs per surgeon and group
      3 had 0.1 CFUs per surgeon. The difference between group 1 and group 2 was
      significant (p<0.001) whereas the difference between group 1 and group 3 was non
      significant (p=0.4). Use of face masks decreased the number of plates with CFUs
      by 93% (from 29 to 2 plates) and decreased the total number of CFUs by 95% (from
      63 to 3 CFUs). The most common microbiota identified was Streptococcus species.
      Conclusions: Oral bacterial microbiota may contaminate the slides and media used
      to collect samples during corneal sampling. Use of a face mask can significantly
      decrease the rate of contamination of such samples.

PMID- 29354702
TI  - Physical inactivity in relation to self-rated eyesight: cross-sectional analysis
      from the English Longitudinal Study of Ageing.
AB  - Background: To assess the cross-sectional association between self-rated eyesight
      and physical activity behaviour in a large general population sample of older
      English adults. Methods: Analyses of data from the English Longitudinal Study of
      Ageing. Participants provided information on self-rated eyesight (categorised as:
      excellent/very good/good/fair-poor) and their own physical activity levels
      (categorised as: inactive/moderate only at least 1/week, vigorous at least
      1/week). Associations between self-rated eyesight and physical activity levels
      were examined using logistic regression. Results: A total of 6634 participants
      (mean age 65.0+/-9.2 years) were included in the analyses. In adjusted logistic
      regression models, those with fair-poor and good eyesight were significantly more
      likely to be inactive than those who reported excellent eyesight (OR 2.07, 95% CI
      1.58 to 2.72; OR 1.59, 1.27 to 1.99, respectively). Conclusion: In this sample of
      older English adults, those with self-rated fair-poor vision were over twice as
      likely to be physically inactive than those who reported having excellent vision.
      When consistent data have emerged, interventions to increase physical activity in
      those who have poor eyesight are needed.

PMID- 29354703
TI  - Pre-eclampsia and the risk of retinopathy of prematurity in preterm infants with
      birth weight <1500 g and/or <31 weeks' gestation.
AB  - Objective: To evaluate the relationship between pre-eclampsia and development of
      retinopathy of prematurity (ROP) in infants with birth weight of <1500 g and/or
      gestation <31 weeks. Methods: A retrospective cohort study comprising infants
      born to mothers with pre-eclampsia between January 2007 and June 2010 at a single
      tertiary care centre. Their ROP outcome was compared with infants born to the
      next two normotensive mothers with a +/-1 week gestational age difference.
      Pearson chi2 test was used for categorical variables and Mann-Whitney U test was
      used for continuous variables. Multivariable regression was used to estimate the
      OR of ROP with prenatal pre-eclampsia exposure and adjust for confounders.
      Results: Of the 97 infants in the pre-eclampsia group, 27 (27%) developed ROP and
      of the 185 infants in the normotensive group, 50 (27%) developed ROP. On
      multivariable regression modelling, pre-eclampsia was not a risk factor for the
      development of ROP (OR 1.4, 95% CI 0.46 to 4.1). Gestational age, intrauterine
      growth restriction and blood transfusion were significant risk factors for the
      development of ROP. Conclusions: In our cohort, pre-eclampsia was not a
      significant risk factor for the development of ROP. Intrauterine growth
      restricted infants of pre-eclamptic and normotensive mothers were at higher risk
      of ROP.

PMID- 29354704
TI  - Therapeutic potential of omega-3 fatty acids supplementation in a mouse model of
      dry macular degeneration.
AB  - Purpose: To evaluate the therapeutic effects of omega-3 (omega-3) and omega-6
      (omega-6) fatty acids in the CCL2-/- model of dry age-related macular
      degeneration (AMD). The blood level of eicosapentaenoic acid (EPA) and
      arachidonic acid (AA) served to adjust the treatment dosage (AA/EPA=1-1.5).
      Methods: Nine-month-old animals were allocated to different groups: (A) C57BL/6
      untreated , (B) CCL2-/- untreated, (C) CCL2-/- treated with omega-3+omega-6, and
      (D) CCL2-/- treated with omega-3. Treatment was daily administered by gavage for
      3 months. Fatty acids analysis was performed and retinas were histologically
      examined. Three-month-old wild type mice were used for comparison purposes. Real
      time PCR and Western blot were performed for retinal inflammatory mediators.
      Results: Increased EPA and decreased AA levels were observed in both blood and
      retinas in the treatment groups. The outer nuclear layer thickness was increased
      in groups C (45.0+/-3.9 um) and D (62.8+/-4.9 um), compared with groups B (65.6+/
      3.0 um) and A (71.1+/-4.2 um), and in younger mice, it was 98.0+/-3.9 um. A
      decrease in NF-kappaB expression was noted in the treatment groups. Interleukin
      (IL) 18 protein levels demonstrated a significant reduction in the omega-3
      treated group only. Conclusion: Supplementation with omega-3+omega-6 or omega-3
      alone (AA/EPA=1-1.5) suggests a protective mechanism in the CCL2-/- animal model
      of dry AMD, with a more beneficial effect when omega-3 are used alone. Our
      findings indicated that inflammation is not the only determining factor; perhaps
      a regenerative process might be involved following administration of omega-3
      fatty acids.

PMID- 29354705
TI  - Vitreoretinal interface abnormalities in middle-aged adults with visual
      impairment in the UK Biobank study: prevalence, impact on visual acuity and
      associations.
AB  - Objective: The aim of this study was to determine the prevalence of vitreoretinal
      interface abnormalities (VRIA), the degree of visual impairment and associations
      with VRIA among adults, aged 40-69 years, in the UK Biobank study. Methods and
      analysis: Colour fundus photographs and spectral domain optical coherence
      tomography images were graded for 25% of the 8359 UK Biobank participants with
      mild visual impairment or worse (LogMAR >0.3 or Snellen <6/12) in at least one
      eye. The prevalence and contribution of VRIA to visual impairment was determined
      and multinomial logistic regression models were used to investigate association
      with known risk factors and other predetermined socioeconomic, biometric,
      lifestyle and medical variables for cases and matched controls. Results: The
      minimum prevalence of any VRIA was 17.6% and 8.1% in the eyes with and without
      visual impairment, respectively. VRIA were identified as the primary cause of
      visual impairment in 3.6% of eyes. Although epiretinal membrane and vitreomacular
      traction were the most common VRIA, the degree of visual impairment was typically
      milder with these than with other VRIA. Visual impairment with a VRIA was
      positively associated with increasing age (relative risk ratio (RRR) 1.22 (95% CI
      1.07 to 1.40)), female gender (RRR 1.28; 1.08 to 1.52) and Asian or Asian British
      ethnicity (RRR 1.60; 1.10 to 2.32). Conclusions: VRIA are common in middle-aged
      adults in the UK Biobank study, especially in eyes with visual impairment. VRIA
      were considered to be the primary cause of visual impairment in 3.6% of all eyes
      with visual impairment, although there was variation in the degree of visual
      impairment for each type of VRIA.

PMID- 29354706
TI  - In vivo crystalline lens measurements with novel swept-source optical coherent
      tomography: an investigation on variability of measurement.
AB  - Objective: To evaluate the reproducibility of in vivo crystalline lens
      measurements obtained by novel commercially available swept-source (SS) optical
      coherence tomography (OCT) specifically designed for anterior segment imaging.
      Methods and analysis: One eye from each of 30 healthy subjects was randomly
      selected using the CASIA2 (Tomey, Nagoya, Japan) in two separate visits within a
      week. Each eye was imaged twice. After image scanning, the anterior and posterior
      lens curvatures and lens thickness were calculated automatically by the CASIA2
      built-in program at 0 dioptre (D) (static), -1 D, -3 D and -5 D accommodative
      stress. The intraobserver and intervisit reproducibility coefficient (RC) and
      intraclass correlation coefficient (ICC) were calculated. Results: The
      intraobserver and intervisit RCs ranged from 0.824 to 1.254 mm and 0.789 to 0.911
      mm for anterior lens curvature, from 0.276 to 0.299 mm and 0.221 to 0.270 mm for
      posterior lens curvature and from 0.065 to 0.094 mm and 0.054 to 0.132 mm for
      lens thickness, respectively. The intraobserver and intervisit ICCs ranged from
      0.831 to 0.865 and 0.828 to 0.914 for anterior lens curvature, from 0.832 to
      0.898 and 0.840 to 0.933 for posterior lens curvature and from 0.980 to 0.992 and
      0.942 to 0.995 for lens thickness. High ICC values were observed for each
      measurement regardless of accommodative stress. RCs in younger subjects tended to
      be larger than those in older subjects. Conclusions: This novel anterior segment
      SS-OCT instrument produced reliable in vivo crystalline lens measurement with
      good repeatability and reproducibility regardless of accommodation stress.

PMID- 29354707
TI  - Oral administration of the 11beta-hydroxysteroid-dehydrogenase type 1 inhibitor
      RO5093151 to patients with glaucoma: an adaptive, randomised, placebo-controlled
      clinical study.
AB  - Background/aims: Cortisol is involved in the regulation of intraocular pressure
      (IOP). This study aimed to assess the effect of 11beta-hydroxysteroid
      dehydrogenase type 1 (11betaHSD1) inhibition by oral administration of RO5093151
      on IOP. Methods: The exposure of key ocular compartments following oral
      administration was assessed in rabbits. An adaptive, randomised, placebo
      controlled study gated by a Bayesian decision criterion was performed in 35
      patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT).
      Following a 7-day placebo-controlled run-in period, 200 mg twice daily RO5093151
      or placebo (4:1) were administered for 7 days. The extent of 11betaHSD1
      inhibition was assessed by the ratio of urinary tetrahydrocortisol (5alpha and
      5beta)/tetrahydrocortisone (THF/THE). Time-matched IOP assessments were
      performed. Results: A high distribution of RO5093151 into the rabbit eye was
      observed. In humans, a high and sustained inhibition of 11betaHSD1 was shown by
      the decrease of THF/THE from 0.9 at baseline to 0.18 on day 7. There was no
      statistically significant difference in change of IOP from baseline. In the
      'worse eye', the adjusted least square mean change from baseline was -2.7 mm Hg
      (95% CI -4.2 to -1.2) and -2.9(95% CI -5.9 to 0.1) in the RO5093151 and placebo
      group, respectively. Conclusions: Despite high inhibition of 11betaHSD1 and
      expected moderate to high tissue distribution in ocular tissues, a 7-day
      treatment with a high oral dose of RO5093151 did not result in a clinically
      meaningful effect on IOP in patients with POAG or OHT.

PMID- 29354708
TI  - Assessment of dysphotopsia in pseudophakic subjects with multifocal intraocular
      lenses.
AB  - Aim: To better understand the phenomenon of dysphotopsia in patients implanted
      with multifocal intraocular lenses (IOLs). Methods: Forty-five patients (aged
      61.8+/-8.9 years) implanted bilaterally with Tecnis ZM900 (diffractive
      multifocal), Lentis Mplus MF30 (segmented refractive multifocal) or Softec-1
      (monofocal) IOLs (each n=15) 4-6 months previously and who had achieved a good
      surgical outcome were examined. Each reported their dysphotopsia symptoms
      subjectively, identified its form (EyeVisPod illustrations), quantified retinal
      straylight (C-Quant) and halo perception (Aston halometer). Retinal straylight
      and halometry was repeated by a second masked clinician to determine
      interobserver repeatability. Results: Subjective dysphotopsia ratings were able
      to differentiate Tecnis ZM900 from Lentis Mplus MF30 (p<0.001), but not Lentis
      Mplus MF30 from groups implanted with Softec-1 (p=0.290). Straylight was similar
      between the monofocal and multifocal IOL designs (p=0.664). ZM900 IOLs
      demonstrated a uniform increase in dysphotopsia in comparison with the monofocal
      IOL (p<0.001) as measured with the halometer, whereas sectorial refractive
      multifocal IOLs demonstrated a localised increase in dysphotopsia over the
      inferior visual field. Intraobserver repeatability was good for the straylight
      (intraclass correlation coefficients (ICC)=0.77) and halometry (ICC=0.89). There
      was no significant correlation between the subjective dysphotopsia severity and
      the straylight (p=0.503) or halometry (p>0.10) quantification or between
      straylight and the halo area (p>0.30). Conclusions: Multifocal IOLs induce
      symptoms of dysphotopsia. Straylight did not differentiate between IOL designs,
      however halometry identified clear differences in light scatter due to the IOL
      optics. Whereas, subjective rating of overall dysphotopsia are not strongly
      associated with straylight or halo perception, the halometry polar diagram
      reflected the subjective descriptions of dysphotopsia.

PMID- 29354709
TI  - Preclinical development of MGO Manuka Honey microemulsion for blepharitis
      management.
AB  - Objective: To evaluate the in vitro antimicrobial effects of cyclodextrin
      complexed and uncomplexed Manuka honey on bacteria commonly associated with
      blepharitis, and in vivo rabbit eye tolerability of a cyclodextrin-complexed
      methylglyoxal (MGO) Manuka Honey microemulsion (MHME). Methods and analysis: In
      vitro phase: Bacterial growth inhibition was assessed by area under the growth
      curve (AUC) for Staphylococcus aureus, and the minimum inhibitory concentration
      (MIC) and minimum bactericidal concentration (MBC) for S. aureus, Staphylococcus
      epidermidis and Pseudomonas aeruginosa with cyclodextrin-complexed and
      uncomplexed Manuka honey were determined. In vivo phase: Six rabbits were
      administered 20 uL of MHME (at 1:10 dilution) to the right eye (treated) and 20
      uL of saline to the left eye (control) daily, for 5 days. Tear evaporation,
      production, osmolarity, lipid layer, conjunctival hyperaemia and fluorescein
      staining were assessed daily, before and 15 min after instillation. Results: In
      vitro phase: The relative AUC for cyclodextrin-complexed Manuka honey was lower
      than that of uncomplexed honey at both 250 and 550 mg/kg of MGO (both p <0.05).
      Cyclodextrin-complexed honey had lower MIC and MBC than uncomplexed honey for
      both S. aureus and S. epidermidis, but not P. aeruginosa. In vivo phase: No
      significant changes were observed in the parameters assessed in either treated or
      control eyes (all p >0.05). Conclusion: Overall, antimicrobial potency of
      cyclodextrin-complexed Manuka honey was greater than uncomplexed honey. No
      significant immediate or cumulative adverse effects were observed with MHME
      application on rabbit eyes, supporting future conduct of clinical safety and
      tolerability trials in human subjects.

PMID- 29354711
TI  - Downregulation of interferon-gamma-induced protein 10 in the tears of patients
      with Stevens-Johnson syndrome with severe ocular complications in the chronic
      stage.
AB  - Objectives: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are acute inflammatory vesiculobullous reactions of the skin and mucosa such as
      the ocular surface, oral cavity and genitals. Severe ocular complications (SOC)
      arise in some patients with SJS/TEN diagnosed by dermatologists. To investigate
      the pathophysiology of ocular surface inflammation in SJS/TEN with SOC in the
      chronic stage, we examined cytokines in the tears of patients with ocular surface
      diseases and healthy controls. Participants: SJS/TEN eyes in the chronic stage
      (n>30), healthy eyes (n>20, controls) and eyes (n>20) from patients with atopic
      keratoconjunctivitis representing different ocular surface inflammatory
      disorders. Primary outcome measures: Tear samples were collected on Schirmer's
      measurement strips. To measure the level of various cytokines in the tears we
      used BD CBA Flex sets. Study design: An observational study (case-control study).
      Results: We recorded the level of interleukin (IL)-6, IL-8, eotaxin, macrophage
      inflammatory protein (MIP)-1beta, RANTES (regulated on activation, normal T cell
      expressed and secreted), interferon gamma (IFN)-gamma, monocyte chemoattractant
      protein-1, IFN-gamma-induced protein 10 (IP-10) and total IgE. We found that
      compared with the controls, in SJS/TEN with SOC, IL-6, IL-8, eotaxin and MIP
      1beta were significantly upregulated while IP-10 was significantly downregulated.
      Compared with atopic keratoconjunctivitis, IP-10 was significantly downregulated
      in SJS/TEN with SOC; on the other hand, total IgE was significantly upregulated
      in atopic keratoconjunctivitis compared with SJS/TEN with SOC. Conclusions: IP-10
      in tears may be a biomarker to distinguish between chronic SJS/TEN with SOC and
      other ocular inflammatory disorders such as atopic keratoconjunctivitis.

PMID- 29354710
TI  - Randomised masked trial of the clinical safety and tolerability of MGO Manuka
      Honey eye cream for the management of blepharitis.
AB  - Objective: To assess the clinical safety and tolerability of a novel MGO Manuka
      Honey microemulsion (MHME) eye cream for the management of blepharitis in human
      subjects. Methods and analysis: Twenty-five healthy subjects were enrolled in a
      prospective, randomised, paired-eye, investigator-masked trial. The MHME eye
      cream (Manuka Health New Zealand) was applied to the closed eyelids of one eye
      (randomised) overnight for 2 weeks. LogMAR visual acuity, eyelid irritation
      symptoms, ocular surface characteristics and tear film parameters were assessed
      at baseline, day 7 and day 14. Expression of markers of ocular surface
      inflammation (matrix metalloproteinase-9 and interleukin-6) and goblet cell
      function (MUC5AC) were quantified using impression cytology at baseline and day
      14. Results: There were no significant changes in visual acuity, eyelid
      irritation symptoms, ocular surface characteristics, tear film parameters and
      inflammatory marker expression during the 2-week treatment period in treated and
      control eyes (all p>0.05), and measurements did not differ significantly between
      eyes (all p>0.05). No major adverse events were reported. Two subjects
      experienced transient ocular stinging, presumably due to migration of the product
      into the eye, which resolved following aqueous irrigation. Conclusion: The MHME
      eye cream application was found to be well tolerated in healthy human subjects
      and was not associated with changes in visual acuity, ocular surface
      characteristics, tear film parameters, expression of markers of inflammation or
      goblet cell function. The findings support future clinical efficacy trials in
      patients with blepharitis. Trial registration number: ACTRN12616000540415.

PMID- 29354712
TI  - Kinetics of Corneal Antigen Presenting Cells in Experimental Dry Eye Disease.
AB  - Objective: To evaluate dry eye disease (DED)-induced alterations in subsets of
      corneal antigen presenting cells (APCs) in a mouse model of experimental DED.
      Methods and Analysis: Seven to 8-week-old female C57BL/6 mice were housed in a
      controlled environment chamber and were treated with subcutaneous scopolamine to
      induce DED. Normal mice were used as controls. The frequencies of different
      subsets of dendritic cells (DCs) and macrophages in the cornea were evaluated
      using immunohistochemistry and flow cytometry at days 2, 7 and 14 after DED
      induction. Real-time PCR was used to assess the functional phenotype of
      macrophages in the cornea of DED mice. Results: Our results demonstrated
      significant corneal infiltration of CD11b+ and CD11c+ cells on days 7 and 14.
      Further analysis of different DC subsets revealed non-significant changes in the
      frequencies of total CD11b+CD11c+ cells at different time points. However,
      frequencies of CD11c+CD11b- DCs, CD11c+ Langerin (CD207)+ DCs and macrophages
      were significantly increased on both days 7 and 14 after DED induction. Real-time
      PCR data demonstrated increased expression of M1 macrophage markers, iNOS and TNF
      alpha, and reduced expression of M2 macrophage markers, Arg1 and IL-10, by
      corneal F4/80+ macrophages at day 7. Conclusion: Although the frequencies of
      total CD11b+CD11c+ cells do not significantly change in the course of DED,
      CD11c+CD11b- DCs and Langerin+ DCs do show a significant increase. Interestingly,
      macrophages exhibit a predominant inflammatory M1 phenotype and suppressed anti
      inflammatory M2 phenotype early after induction of DED, which are restored to
      near baseline levels in later stages of the disease.

PMID- 29354713
TI  - Use of four asymmetric marks to orient the donor graft during Descemet's membrane
      endothelial keratoplasty.
AB  - Introduction: Maintaining the correct orientation of the donor graft is important
      during Descemet's membrane endothelial keratoplasty (DMEK). We describe a new
      method of marking the donor graft prior to DMEK. Methods: Twelve eyes of 10
      patients with bullous keratopathy who underwent DMEK were retrospectively
      analysed. Donor discs were created by stripping the endothelium-Descemet's
      membrane layer from corneoscleral buttons. Four semicircular marks, two 1.0 mm
      and two 1.5 mm in diameter, were created at the edge of the donor disc. The small
      and large marks were paired. Each donor graft was inserted into the anterior
      chamber, unfolded and attached to the posterior corneal stroma with an air
      bubble. Results: The inserted grafts were all appropriately orientated when
      attached to the back surfaces of the corneas. The two pairs of asymmetric marks
      afforded valuable guidance. Even when the graft was partially folded or
      decentred, and one pair of marks was obscured, the other pair was always visible
      to indicate graft orientation. Best spectacle-corrected visual acuity improved
      significantly in all patients (p<0.001). Compared with the preoperative
      endothelial cell density of the donor graft, that of the corneal endothelium had
      decreased 44.0%+/-10.0% by 6 months after surgery. Conclusions: Two pairs of
      asymmetrical semicircular marks placed on the edge of the donor graft allowed
      appropriate graft orientation during DMEK.

PMID- 29354714
TI  - Diabetic retinopathy screening and treatment in Myanmar: a pilot study.
AB  - Background/aims: The goals of this pilot study were (a) to demonstrate the
      feasibility of identifying patients with vision-threatening diabetic retinopathy
      (DR) in a provincial area of Myanmar and treating them with portable lasers and
      (b) to gather data specific to Myanmar to help design larger cross-sectional
      studies of DR prevalence in Myanmar. Methods: 97 consecutive patients with
      diabetes mellitus (DM) were identified by local ophthalmologists over a period of
      1 month in Pyinmana, Myanmar and were referred to the pilot screening programme.
      Patients' demographics were recorded and their eyes were examined. Those with
      vision-threatening DR were treated with panretinal photocoagulation (PRP).
      Results: Of the 97 patients with DM, 33 (34%) had evidence of DR, 23 (23.5%) had
      evidence of vision-threatening DR including 13 (13.5%) with proliferative DR and
      33 eyes in 23 patients (23.5%) had PRP with portable green wavelength laser.
      Hypertension was a significant cofactor in the development of vision-threatening
      DR (p<0.01). The average time since diagnosis of DM was 6.0 years in patients
      with vision-threatening DR. Conclusions: This study demonstrates the feasibility
      of identifying and treating patients with vision-threatening DR in a provincial
      area of Myanmar and provides initial data to plan a larger study to assess true
      prevalence, a prerequisite for establishing broader screening/treatment programs.

PMID- 29354715
TI  - Microbial keratitis and the selection of topical antimicrobials.

PMID- 29354716
TI  - Diabetic retinopathy and the use of laser photocoagulation: is it cost-effective
      to treat early?
AB  - Background/aims: The aim of the study was to explore whether it would be cost
      effective to apply panretinal photocoagulation (PRP) at the severe non
      proliferative diabetic retinopathy (NPDR) (early treatment) stage, compared with
      waiting until high-risk proliferative diabetic retinopathy (HR-PDR)
      characteristics (deferred treatment) developed. Methods: A Markov model with a 30
      year time horizon was developed, in which patients presenting with moderate NPDR
      could progress through all stages of DR (severe NPDR>early PDR>HR-PDR>severe PDR)
      to severe vision loss and blindness (and to death). A National Health Service and
      personal social services perspective was adopted. Transition probabilities were
      mainly derived from the Early Treatment Diabetic Retinopathy Study. Health state
      utilities, costs and complications were based on information from the literature,
      supplemented by expert opinion. Costs and outcomes were discounted at 3.5%. Both
      deterministic and probabilistic sensitivity analyses were conducted. Results:
      Administering PRP at the severe NPDR stage could be more effective and less
      costly than waiting until HR-PDR developed. Sensitivity analyses gave similar
      results, with early treatment continuing to dominate deferred treatment. The
      probabilistic sensitivity analysis suggests that at willingness-to-pay threshold
      of L20-L30 000 per quality-adjusted life year, the probability of early treatment
      being cost-effective is 60%. Conclusion: PRP administered at the severe NPDR
      stage is likely to be cost-effective compared with delaying photocoagulation
      until HR-PDR develops. However, given the limitations of the evidence, these
      results need to be interpreted with caution. A trial of early versus deferred
      laser therapy is needed to provide better data based on modern treatments.

PMID- 29354717
TI  - Correlation between baseline retinal microstructures in spectral-domain optic
      coherence tomography and need for early intervention in central serous
      chorioretinopathy.
AB  - Purpose: To investigate the association between baseline retinal microstructures
      observed with spectral-domain optical coherence tomography (OCT) and the need for
      early intervention in central serous chorioretinopathy (CSC). Methods: Cases of
      acute CSC from July 2011 to December 2014 were retrospectively reviewed. OCT
      images were further classified using six parameters: foveal serous retinal
      detachment; pigment epithelial detachment; fibrinous exudates in the subretinal
      space; retinal pigment epithelium bumps; thickened outer retinal layer and hyper
      reflective dots in the intraretinal and/or subretinal layer. Correlation among
      these parameters and the need for intervention was analysed. Receiver operating
      characteristic (ROC) curves were performed to identify the optimal number of
      parameters for prediction. Results: A total of 47 eyes from 47 patients were
      included. Among these, 25 eyes required treatment. The presence of subretinal
      hyper-reflective dots was the only OCT factor having significant association with
      the need for intervention. An ROC curve analysis revealed that the optimal cut
      off value (Youden index) was achieved when combining subretinal hyper-reflective
      dots with aged >=50 years and female sex for analysis (area under the curve,
      0.735; Youden index: 0.425). Conclusion: The presence of subretinal/intraretinal
      hyper-reflective dots observed with OCT, female and aged >=50 years might help
      predict the need for early intervention in acute CSC.

PMID- 29354718
TI  - Efficacy and safety of an extemporaneous preparation of 2% ganciclovir eye drops
      in CMV anterior uveitis.
AB  - Background: To evaluate the efficacy and safety of an extemporaneous preparation
      of 2% ganciclovir topical eye drops in cytomegalovirus (CMV) anterior uveitis
      because many studies have confirmed the benefits of topical ganciclovir in
      varying concentrations. Design: The study employed a retrospective cohort design.
      Methods: This study enrolled 11 eyes (11 patients) with CMV anterior uveitis. All
      cases were proved by positive PCR for CMV DNA from aqueous tapping and received
      topical 2% ganciclovir, applied every 2 hours daily as induction therapy then
      tapered off and stopped based on clinical response. Outcome measures were best
      corrected visual acuity, anterior chamber cell, coin-shaped and other keratic
      precipitates, intraocular pressure (IOP), the number of antiglaucoma drugs used,
      the frequency of steroid eye drops used daily and side effects over a 12-month
      follow-up period. Side effects after applying topical 2% ganciclovir were
      recorded using questionnaires and eye examination. Results: Mean age was 49.0+/
      17.8 years. IOP, number of antiglaucoma drugs used and keratic precipitates
      decreased significantly at first week (p<0.013, p<0.024 and p<0.031,
      respectively) followed by decreased anterior chamber cells and significantly
      reduced frequency of applying steroid eye drops at 4 weeks (p<0.034 and p<0.017,
      respectively). Visual acuity significantly improved at 5 months continuously. All
      clinical improvement was maintained to 12 months, and keratic precipitates were
      eliminated in 90% of all cases. However, in 27% of discontinued medicine cases,
      inflammation was recurrent. No significance was observed in all factors between
      recurrent and non-recurrent groups. The most common side effect was eye
      irritation (27.27%). No severe complications from the medicine was detected.
      Conclusion: Extemporaneous preparation topical 2% ganciclovir was effective and
      safely controlled CMV anterior uveitis. The medication is non-invasive,
      economical and convenient for hospitals where commercial topical ganciclovir is
      unavailable.

PMID- 29354719
TI  - Fixation stability of the upward gaze in patients with myasthenia gravis: an eye
      tracker study.
AB  - Objective: To quantify fixation stability of the upward gaze in patients with
      myasthenia gravis (MG) using an eye tracker. Methods and analysis: In this study,
      21 normal subjects, 5 patients with MG with diplopia, 5 patients with MG without
      diplopia and 6 patients with superior oblique (SO) palsy were included. Subjects
      fixated on a target in the upward direction for 1 min. The horizontal (X) and
      vertical (Y) eye positions were recorded using an eye tracker. Fixation stability
      was first quantified using the bivariate contour ellipse areas (BCEA) of fixation
      points as an index of whole stability. Then, the SDs of the X and Y eye positions
      (SDX and SDY, respectively) were quantified as indices of directional stability,
      with the data divided into three 20 s fractions to detect temporal fixation
      fluctuation. Results: BCEAs were larger in patients with MG (both with and
      without diplopia) than normal subjects and patients with SO palsy, without
      significant differences among the three 20 s fractions. Compared with normal
      subjects, SDXs were larger only in patients with MG with diplopia; SDYs were
      larger in both patients with MG with and without diplopia. In addition, SDYs in
      patients with MG with diplopia were larger than those in patients with MG without
      diplopia and patients with SO palsy. Furthermore, a significant difference among
      the three 20 s fractions was detected for SDYs in patients with MG with diplopia.
      Conclusion: Patients with MG, especially those with diplopia, exhibit fixation
      instability in the upward gaze. Non-invasive quantification of fixation stability
      with an eye tracker is useful for precisely identifying MG-specific fatigue
      characteristics. Trial registration number: UMIN000023468; pre-results.

PMID- 29354721
TI  - Method for sterility testing of corneal storage and transport media after removal
      of interfering antimicrobials: prospective validation study in compliance with
      the European Pharmacopoeia.
AB  - Objective: This study aimed at validating the method for sterility testing of the
      corneal culture medium, TISSUE-C, and the transport/deswelling medium, CARRY-C,
      according to the method suitability test, as defined by the European
      Pharmacopoeia (EP), using RESEP, which is a new medical device for removal of
      antimicrobial agents and an automated culture system. Methods and analysis: The
      six EP reference strains were inoculated in TISSUE-C and CARRY-C. Half of the
      samples were treated with RESEP (RESEP+ group) prior to the sterility testing,
      whereas the remaining samples were untreated (RESEP- group). Growth controls were
      obtained by direct inoculation of the micro-organisms in the culture broths.
      Microbial growth was read by an automated light scattering culture system within
      48 hours. Results: The use of RESEP allowed detection of microbial growth in 100%
      of the tested samples, with a mean time to detection (TTD) comparable with that
      of the growth control group. Significantly lower sensitivity (38.83%+/-20.03% for
      both media, P<0.05) and TTD variability, depending on the tested micro-organism,
      were observed in the RESEP- group. The method specificity was 100% for both
      groups. Conclusion: The use of RESEP increased the sensitivity of the sterility
      testing method to 100% and, for the first time, allowed validation of the method
      for sterility testing of corneal storage media according to the EP method
      suitability test. This further increases the safety of the corneas intended for
      transplantation.

PMID- 29354720
TI  - Comparative analysis of the visual performance after implantation of the toric
      implantable collamer lens in stable keratoconus: a 4-year follow-up after
      sequential procedure (CXL+TICL implantation).
AB  - Aims: To report on 4-year postoperative visual performance with the toric
      implantable collamer lens (TICL) for stable keratoconus after sequential
      procedure (corneal collagen crosslinking plus TICL implantation). Methods: Forty
      eyes of 24 patients with stable keratoconus with myopia between 0.00 and -18.00
      dioptres (D) and astigmatism between 1.25 and 8.00 D were evaluated in this
      prospective interventional study
      (https://clinicaltrials.gov/ct2/show/NCT02833649). We evaluated refraction,
      visual outcomes, astigmatic changes analysed by Alpins vector, contrast
      sensitivity, aberrometry, modulation transfer functions (MTFs), defocus curve,
      and operative and postoperative complications. Results: At 4-year follow-up, 45%
      had 20/20 vision or better and 100% had 20/40 or better uncorrected visual acuity
      (UCVA). Vector analysis of refractive astigmatism shows that the surgically
      induced astigmatism (SIA) (3.20+/-1.46 D) was not significantly different from
      the target induced astigmatism (TIA) (3.14+/-1.42 D) (p=0.620). At 4 years
      postoperatively, none of the eyes showed a decrease in UCVA, in contrast to 24
      eyes in which UCVA was increased by >=1 lines, with contrast sensitivity and
      improvement in total aberrations and MTF value at 5 per degree (*p=0.004) after
      TICL implantation. The cumulative 4-year corneal endothelial cell loss was <=5%.
      No patients reported dissatisfaction. At the end of follow-up, the vault was
      658+/-54.33m (range, 500-711) and the intraocular pressure was 11.7+/-2.08 mm Hg.
      Occurrences of glare and night-driving troubles diminished after TICL surgery.
      Conclusion: The results from this standardised clinical investigation support
      TICL implantation from clinical and optical viewpoints in patients with stable
      keratoconus. Trial registration number: NCT02833649, Pre-results.

PMID- 29354722
TI  - Transcorneal electrical stimulation for the treatment of retinitis pigmentosa:
      results from the TESOLAUK trial.
AB  - Objective: To explore the impact of weekly transcorneal electrical stimulation
      (TES) over a 6-month period as a treatment for retinitis pigmentosa (RP). Methods
      and analysis: A prospective open-label observational trial was carried out
      assessing weekly TES in participants with RP for a period of 6 months followed by
      observation for a further 6 months. Clinical examination and investigations were
      carried out at 3 monthly intervals for a total of 12 months. The primary outcome
      measure explored safety through a descriptive analysis of adverse effects with
      secondary outcome measures evaluating structural and functional efficacy.
      Results: Seven male and seven female participants with RP aged 18-80 years were
      recruited. TES was well tolerated with no serious adverse events reported. Two
      participants reported transient foreign body sensation and one participant had
      discomfort underneath the skin electrode. Following 6 months of TES, best
      corrected visual acuity increased by 1.1+/-1.4 letters in the control arm and
      0.93+/-1.4 letters in the treated arm. Central microperimetry threshold
      sensitivity rose by 0.02+/-0.5 decibels (dB) and 0.37+/-0.4 dB and Goldmann
      visual field volume by 0.16+/-0.09 steradians (sr) vs 0.22+/-0.12 sr for the
      control and treated eye, respectively. There was no statistical significance seen
      between eyes following the treatment or observation period. Conclusion: This
      small open-label clinical trial showed that TES was safe and well tolerated in
      patients with RP. Visual function measurements at 6 months demonstrated no
      significant difference between the control and treated eyes. The results justify
      a larger clinical trial over a longer period of time in order to identify any
      treatment effect.

PMID- 29354723
TI  - Results of a community-based screening programme for diabetic retinopathy and
      childhood blindness in district Hyderabad, Pakistan.
AB  - Purpose: To present the results of a community-based screening programme for
      diabetes, diabetic retinopathy (DR) and childhood blindness (CB) in District
      Hyderabad, Pakistan. Methods: Prospective cross-sectional data collection from
      January 2014 to December 2015 of screening for diabetes, DR and CB in Hyderabad
      District. Female health workers were trained to identify high-risk (potential)
      patients for diabetes and childhood eye disorders to undertake preliminary
      screening and refer patients to basic health units. The patients were further
      assessed by medical officers with the support of qualified optometrist, after
      which they were referred to Sindh Institute of Ophthalmology and Visual Sciences,
      Hyderabad, Pakistan for management. Results: A total of 995 244 population was
      covered in this screening programme during which 2622 children (0-<=15 years)
      were screened for CB while 16 760 adult patients (>15 years) were screened for
      diabetes. Random blood glucose level of 3075 patients was >140 mg/dL. Out of
      these patients, 17% were diagnosed with DR. Refractive error (42%) was the most
      common cause of childhood visual impairment. Conclusion: The diabetic screening
      programme detected a high prevalence (17%) of retinopathy in patients with
      diabetes living in Hyderabad District. The most common cause of childhood visual
      impairment was refractive error (42%), which was successfully managed due to
      timely diagnosis. A large number of patients benefited from this community-based
      screening programme.

PMID- 29354724
TI  - Development and pilot-testing of patient decision aid for use among Chinese
      patients with primary open-angle glaucoma.
AB  - Background: A patient decision aid (PDA) is a tool for shared decision making
      (SDM), which emphasises patient empowerment. It is useful in chronic diseases and
      when there are multiple, no best single treatment option. Although SDM is
      prevalent in Western countries, its use is limited in Chinese societies, where
      the adoption of a paternalistic approach is strong. Here, we report the
      development, acceptance and pilot test results of a PDA targeted at Chinese
      patients with primary open-angle glaucoma (POAG). Methods: We developed a PDA
      designed for use in Chinese patients with POAG. Recruited subjects were given our
      PDA. Baseline evaluation included decision conflict scale (DCS), validated
      glaucoma adherence questionnaires and glaucoma knowledge questionnaire. Subjects
      were briefed through the PDA and instructed to read it that day. Three to four
      weeks later, follow-up questionnaire as described above were conducted with the
      addition of acceptance questionnaires. Results: Data from 65 subjects were
      available. The PDA was well received among subjects. DCS improved from 48.9+/
      20.4 at baseline to 34.3+/-20.3 during follow-up, with P<0.01. Validated
      medication adherence questionnaires and knowledge showed improvement from
      baseline, which was statistically significant. Conclusions: The use of PDA among
      Chinese subjects with POAG demonstrated positive reception and acceptance.
      Evaluation of its initial effects shows improvement in DCS, medication adherence
      and glaucoma knowledge. The implementation of SDM and PDA among Chinese subjects
      with POAG is encouraged. Future studies with randomised design and later
      evaluation time points can further reveal the impacts of PDA among Chinese
      subjects with POAG.

PMID- 29354725
TI  - Neither non-toxigenic Staphylococcus aureus nor commensal S. epidermidi activates
      NLRP3 inflammasomes in human conjunctival goblet cells.
AB  - Purpose: The conjunctiva is a wet mucosal surface surrounding the cornea that is
      continuously exposed to pathogens. Nevertheless, persistent inflammation is not
      observed. We examined if the NOD-like receptor pyrin domain 3 (NLRP3)
      inflammasome functions as a sensor that distinguishes commensal and non
      pathogenic bacteria from pathogenic bacteria in human conjunctival goblet cells.
      Methods: Goblet cells were grown from human conjunctiva and co-cultured with
      commensal Staphylococcus epidermidis, isogenic non-toxigenic S. aureus ACL135 and
      as a control toxigenic S. aureus RN6390. Activation of the NLRP3 inflammasome was
      determined by measuring changes in NF-kappaB activity, expression of pro
      interleukin (IL)-1beta and NLRP3, activation of caspase-1 and secretion of mature
      IL-1beta. Goblet cell mucin secretion was measured in parallel. Results: While
      all three strains of bacteria were able to bind to goblet cells, neither
      commensal S. epidermidis nor isogenic non-toxigenic S. aureus ACL135 was able to
      stimulate an increase in (1) NF-kappaB activity, (2) pro-IL-1beta and NLRP3
      expression, (3) caspase-1 activation, (4) mature IL-1beta and (5) mucin
      secretion. Toxigenic S. aureus, the positive control, increased these values:
      knockdown of NLRP3 with small interfering RNA (siRNA) completely abolished the
      toxigenic S. aureus-induced expression of pro-IL-1beta and secretion of mature IL
      1beta. Conclusions: We conclude that NLRP3 serves as a sensor capable of
      discriminating commensal and non-pathogenic bacteria from pathogenic bacteria in
      conjunctival goblet cells, and that activation of the NLRP3 inflammasome induced
      by pathogenic bacteria mediates secretion of both mature IL-1beta and large
      secretory mucins from these cells.

PMID- 29354726
TI  - Outcomes and complications of S2 alar iliac fixation technique in patients with
      neuromuscular scoliosis: experience in a third level pediatric hospital.
AB  - Background: Multiple techniques are utilized for distal fixation in patients with
      neuromuscular scoliosis. Although there is evidence of benefit with S2 alar iliac
      (S2AI) fixation, this remains controversial. The objective of this study is to
      evaluate the radiological outcomes and complications associated with this
      surgical technique in a pediatric population. Methods: An observational
      retrospective case series study was performed. All pediatric patients between
      January 2011 and February 2014 diagnosed with neuromuscular scoliosis associated
      with pelvic obliquity, which required surgery with fixation unto S2AI, were
      included. Clinical, radiological findings, and adverse events were presented with
      measures of central tendency. Comparison of deformity correction was carried out
      using a non-parametric analysis for related samples (Wilcoxon signed-rank test).
      Significance was set at P<0.05. Results: A total of 31 patients diagnosed with
      neuromuscular scoliosis that met inclusion criteria were analyzed. The leading
      cause of neuromuscular scoliosis in 23 (74.2%) patients was spastic cerebral
      palsy (CP). The correction of pelvic obliquity in the immediate postoperative
      period was of 76%, which is statistically significant. The extent of correction
      that patients maintained at the end of the follow-up was analyzed, and it was
      found that there were no significant differences in this magnitude, compared with
      the immediate postoperative pelvic obliquity. The mean follow-up time was 9+/-7
      months. Regarding postoperative adverse events, occurred in 64.5% of patients,
      the most common outcome was pneumonia (14.8%). The overall rate of complications
      related to instrumentation was low (1.9%), which corresponds to one patient with
      an intra-articular screw in the left hip that required repositioning.
      Conclusions: S2AI fixation for the treatment of neuromuscular scoliosis is a safe
      alternative, in which the onset of adverse events is related to the comorbidities
      of patients instead of the surgical procedure itself. An approximate correction
      of 76% of pelvic obliquity is maintained during the follow-up.

PMID- 29354727
TI  - Does the law of diminishing returns apply to the lengthening of the MCGR rod in
      early onset scoliosis with reference to growth velocity?
AB  - Background: This study is a single centre retrospective review of prospectively
      collected data. The 'law of diminishing returns' describes the number of
      lengthening episodes that a traditional growth rod (TGR) can undergo before
      stiffness across the construct prevents further increases in overall length. It
      is unclear whether this will affect MCGR when used in the management of early
      onset scoliosis (EOS). Methods: A retrospective review of prospectively collected
      data on the experience of MCGR lengthening in a heterogenous cohort of children
      with EOS from a single centre. Results: There were 53 MCGRs in 28 patients with
      EOS with a number of different underlying diagnoses. The mean age of the cohort
      was 8 years 3 months (SD, 2 years 7 months). The mean follow-up period since
      primary rod implantation was 2 years 0 months (SD, 1 year 1 month). MCGR
      lengthening was performed on up to 12 occasions [median, 4; interquartile range
      (IQR), 4; range, 1-12]. There was no statistically significant difference in the
      amount of length achieved over then number of lengthening episodes (P=0.427). For
      those with at least 2 years follow up the median number of lengthening was 10
      (IQR 2, range 9-12) and there was no statistically significant difference seen
      (P=0.438). Growth velocity of MCGRs against age was less than previously
      documented norms for the thoracic spine, but was maintained as age increased.
      Conclusions: The 'law of diminishing returns' does not affect serial lengthening
      of MCGR in the way that has been observed using TGR. It was also demonstrated
      that in the MCGR group growth velocity was maintained relative to that of the
      normal spine.

PMID- 29354728
TI  - Efficacy of tranexamic acid in reducing blood loss and blood transfusion in
      idiopathic scoliosis: a systematic review and meta-analysis.
AB  - Background: Tranexamic acid is a synthetic lysine-analogue antifibrinolytic that
      competitively inhibits the activation of plasminogen to plasmin, it is a well
      documented blood sparing agent. However, its routine use in idiopathic scoliosis
      surgery is poorly documented. The objective of this meta-analysis was to
      determine TXA's efficacy in reducing blood loss and blood transfusion in
      idiopathic scoliosis surgery. Methods: Five databases (Medline, PubMed, Web of
      Science, Embase and The Cochrane Central Register of Controlled Trials) were
      searched to identify the relevant randomized controlled trials (RCTs),
      prospective cohort control (PCC), and retrospective controlled trails regarding
      the TXA efficacy in idiopathic scoliosis surgery. Mean differences (MDs) of blood
      loss and blood transfusions in TXA-treated group compared to control and/or
      placebo group were extracted and combined using random-effect meta-analysis
      model. Results: A total of seven studies comprising 426 patients were included in
      the meta-analysis according to the pre-defined selection criteria. TXA-treated
      group had an overall significantly (P<0.005) less volume of blood loss [ES (MD)
      =727.71 mL; CI, 281.86-1,173.56 mL]. Six studies comprising 346 patients TXA
      treated group had an overall significantly {P<0.001 less transfusion volume [ES
      (MD) =268.30 mL; CI, 105.19-431.44 mL]}. Conclusions: Patients treated with TXA
      had a significantly lower blood loss and lower rates of allogeneic blood
      transfusion than the control group. Further investigation is required regarding
      the safety of TXA before it can be generalized in the use of idiopathic scoliosis
      surgery.

PMID- 29354729
TI  - Radiological factors affecting post-operative global coronal balance in Lenke 5 C
      scoliosis.
AB  - Background: Lenke 5 C curves are frequently associated with clinically and
      radiological coronal imbalance. Appropriate selection of proximal and distal
      levels of fusion is essential to ensure good coronal balance (CB). We aimed to
      evaluate radiological factors associated with (I) global CB in the early post
      operative period; (II) late decompensation of CB; and (III) favourable
      spontaneous correction of CB on long term follow up. Methods: Twenty-three Lenke
      type 5C scoliosis cases treated with selective posterior lumbar instrumentation
      were retrospectively evaluated. Pre-operative, early post-operative and late post
      operative (>2 years) whole length radiographs were analysed. Cobb's angle, lumbar
      lordosis, coronal imbalance, lower instrumented vertebra (LIV) tilt and
      translation and upper instrumented vertebra (UIV) tilt and translation were
      measured. The proximal and distal fusion levels were noted and correlated with
      post-operative CB. Results: There were 21 females and 2 males with a mean follow
      up of 36 months. The mean pre-operative cobb angle was 55 degrees +/-13.26
      degrees , which corrected to 14.7 degrees +/-8.84 degrees  and was maintained on
      follow up. Eight patients had early post-operative coronal imbalance with
      spontaneous resolution seen in six cases on long term follow-up. At final follow
      up, four cases had coronal imbalance (persistent imbalance since early post
      operative period =2; late decompensation =2). In cases with early imbalance 5/8
      cases had a pre-operative LIV tilt of >=25 degrees . All four patients with
      coronal imbalance at final follow-up had pre-operative LIV tilt >=25 degrees .
      Radiographic parameters which correlated with post-operative coronal imbalance
      were pre-operative LIV tilt (r=0.64, P=0.001), pre-operative LIV translation
      (r=0.696, P<0.001), pre-operative UIV translation (r=0.44, P=0.030), post
      operative LIV tilt (r=0.804, P<0.001), and post-operative UIV tilt (r=0.62,
      P=0.001). Conclusions: In Lenke 5C scoliosis, a pre-operative LIV tilt >=25
      degrees  significantly correlates with post-operative global coronal imbalance.
      Increasing UIV tilt may be a factor that accounts for improvement of CB in late
      follow-up period.

PMID- 29354730
TI  - Assessing the effects of lumbar posterior stabilization and fusion to vertebral
      bone density in stabilized and adjacent segments by using Hounsfield unit.
AB  - Background: Computed tomography (CT) with Hounsfield unit (HU) is being used with
      increasing frequency for determining bone density. Established correlations
      between HU and bone density have been shown in the literature. The aim of this
      retrospective study was to determine the bone density changes of the stabilized
      and adjacent segment vertebral bodies by comparing HU values before and after
      lumbar posterior stabilization. Methods: Sixteen patients who had similar
      diagnosis of lumbar spondylosis and stenosis were evaluated in this study. Same
      surgical procedures were performed to all of the patients with L2-3-4-5
      transpedicular screw fixation, fusion and L3-4 total laminectomy. Bone mineral
      density measurements were obtained with clinical CT. Measurements were obtained
      from stabilized and adjacent segment vertebral bodies. Densities of vertebral
      bodies were evaluated with HU before the surgeries and approximately one year
      after the surgeries. The preoperative HU value of each vertebra was compared with
      postoperative HU value of the same vertebrae by using statistical analysis.
      Results: The HU values of vertebra in the stabilized and adjacent segments
      consistently decreased after the operations. There were significant differences
      between the preoperative HU values and the postoperative HU values of the all
      evaluated vertebral bodies in the stabilized and adjacent segments. Additionally
      first sacral vertebra HU values were found to be significantly higher than lumbar
      vertebra HU values in the preoperative group and postoperative group.
      Conclusions: Decrease in the bone density of the adjacent segment vertebral
      bodies may be one of the major predisposing factors for adjacent segment disease
      (ASD).

PMID- 29354731
TI  - The Low-Back Outcome Scale and the Oswestry disability index: are they reflective
      of patient satisfaction after discectomy? A cross sectional study.
AB  - Background: The Low-Back Outcome Scale (LBOS) of Greenough and Fraser and the
      Oswestry disability index (ODI) were compared to the patient satisfaction index
      (PSI) in lumbar disc herniation (LDH) surgery. Methods: A total of 134 patients
      who underwent discectomy were followed through assessment of pre- and post
      surgical satisfaction by the PSI, the LBOS, and the ODI. The LBOS were rated as
      satisfied if the outcomes were excellent or good and as dissatisfied if fair and
      poor. Considering the ODI, clinically satisfied was defined as a 13-point
      improvement from the baseline ODI scores. Phi (Phi) correlation analysis was used
      to study the correlation among the PSI, the LBOS and the ODI scores as proxy for
      patients' satisfaction. Results: Mean age of patients was 48.9 years. Significant
      improvement from the pre- to post-operative ODI scores was observed. Post
      surgical satisfaction based on the PSI, the ODI, and the LBOS were 70.9%, 76.8%,
      and 81.3%, respectively. Regarding patient satisfaction, there were weak
      associations between LBOS vs. PSI and ODI vs. PSI (Phi=-0.054, P=0.533) and (Phi=
      0.129, P=0.136), respectively. Conclusions: Our study showed that the ODI and the
      LBOS were not reflective of patients' satisfaction after discectomy.

PMID- 29354732
TI  - C7 intra-laminar screws for complex cervicothoracic spine surgery-a case series.
AB  - Background: C7 has relatively unique anatomy compared to the remainder of the
      subaxial cervical spine (C3-C6) and upper thoracic spine. The C7 laminar has been
      previously reported in feasibility and biomechanical studies as an adequate
      fixation point in contrast to the lateral mass or pedicles, with few reports of
      its use in clinical practice. The purpose of this study was to review the safety
      and efficacy of using the C7 laminar as a fixation point in constructs involving
      the cervical spine and cervicothoracic junction. Methods: Between February 2013
      and July 2016, 10 patients (6 males, 4 females) had 19 C7 intra-laminar screws
      sited (bilateral in 9 patients, unilateral in 1 patient). Six patients had trauma
      as an underlying etiology, 2 of which had pseudoarthrosis from prior surgery.
      Three patients had cervical myelopathy from degenerative disease, 2 of which
      required anterior and posterior instrumentation for correction of deformity and 1
      which had stand-alone posterior fixation. One patient had stabilization for an
      underlying malignancy. Results: One patient died 2 weeks following their high
      cervical injury secondary to complications of respiratory failure. None of the
      remaining 9 patients were noted to have construct failure at a median follow up
      of 1 year (range, 6 months to 4 years) and all were noted to have satisfactory
      positioning of the instrumentation on post-operative imaging. The patient with
      malignancy died 6 months later from extra-spinal disease, there was one wound
      breakdown requiring debridement without infection in a revision case, and one
      patient required laminectomy for post-traumatic syrinx formation. Conclusions:
      The C7 laminar provides an alternative fixation point for constructs involving
      the subaxial cervical spine and cervicothoracic junction, with excellent safety
      and efficacy in this small series. Larger series are required to more clarify the
      risk profile of this technique.

PMID- 29354734
TI  - Use of 3D printer model to study vertebral artery anatomy and variations in
      developmental craniovertebral junction anomalies and as a preoperative tool-an
      institutional experience.
AB  - Background: Spinal instrumentation using rods and screws have become procedure of
      choice for posterior fixation. Vertebral artery anatomy is highly variable in
      this region posing challenges during surgery. Our study used 3D printer model to
      understand the anatomy and variations in vertebral artery in live patients
      thereby providing an accurate idea about vertebral artery injury risk in these
      patients preoperatively and to rehearse the whole procedure. Methods: Ten
      patients of developmental craniovertebral junction (CVJ) anomalies who were
      planned for operative intervention in the Department of Neurosurgery at SMS
      Hospital from February 2016 to December 2016 were analysed using a 3D printer
      model. Results: Out of twenty vertebral arteries studied in ten patients, two
      were hypoplastic and out of these one could not be appreciated on 3D printer
      model. Out of remaining nineteen, thirteen arteries were found to lie outside the
      joint, three were in lateral third, one traversed the middle third of joint and
      one lied in medial third. In one patient, the vertebral artery was stretched and
      it traversed horizontally over the joint. Out of ten patients studied, nine were
      having occipitalised atlas and so entry of these vertebral arteries into cranium
      were classified as given by Wang et al. into four types. Conclusions: By our
      study, 3D printer model was extremely helpful in analyzing joints and vertebral
      artery preoperatively and making the surgeon acquainted about the placement and
      trajectory of the screws accordingly. In our opinion, these models should be
      included as a basic investigation tool in these patients.

PMID- 29354733
TI  - Does timing of transplantation of neural stem cells following spinal cord injury
      affect outcomes in an animal model?
AB  - Background: We previously reported that functional recovery of rats with spinal
      cord contusions can occur after acute transplantation of neural stem cells distal
      to the site of injury. To investigate the effects of timing of administration of
      human neural stem cell (hNSC) distal to the site of spinal cord injury on
      functional outcomes in an animal model. Methods: Thirty-six adult female Long
      Evans hooded rats were randomized into three experimental and three control
      groups with six animals in each group. The T10 level was exposed via posterior
      laminectomy, and a moderate spinal cord contusion was induced by the Multicenter
      Animal Spinal Cord Injury Study Impactor (MASCIS, W.M. Keck Center for
      Collaborative Neuroscience, Piscataway, NJ, USA). The animals received either an
      intrathecal injection of hNSCs or control media through a separate distal
      laminotomy immediately, one week or four weeks after the induced spinal cord
      injury. Observers were blinded to the interventions. Functional assessment was
      measured immediately after injury and weekly using the Basso, Beattie, Bresnahan
      (BBB) locomotor rating score. Results: A statistically significant functional
      improvement was seen in all three time groups when compared to their controls
      (acute, mean 9.2 vs. 4.5, P=0.016; subacute, mean 11.1 vs. 6.8, P=0.042; chronic,
      mean 11.3 vs. 5.8, P=0.035). Although there was no significant difference in the
      final BBB scores comparing the groups that received hNSCs, the group which
      achieved the greatest improvement from the time of cell injection was the
      subacute group (+10.3) and was significantly greater than the chronic group
      (+5.1, P=0.02). Conclusions: The distal intrathecal transplantation of hNSCs into
      the contused spinal cord of a rat led to significant functional recovery of the
      spinal cord when injected in the acute, subacute and chronic phases of spinal
      cord injury (SCI), although the greatest gains appeared to be in the subacute
      timing group.

PMID- 29354735
TI  - Functional outcomes of laminectomy and laminotomy for the surgical management
      lumbar spine stenosis.
AB  - Background: This clinical descriptive study aims to establish if differences
      exist in functional outcomes, to include both leg and lower back pain (LBP) as
      well as disability, in patients undergoing laminectomy or laminotomy surgery for
      lumbar spinal stenosis (LSS). Methods: We conducted a single centre, prospective
      study of 119 patients undergoing laminectomy or laminotomy surgery for LSS, from
      2006 and 2012. Clinical outcomes for back and leg pain were analyses using
      Oswestry Disability Index (ODI) questionnaires and visual analogue scale (VAS)
      scores collected preoperatively, at 6 weeks and 1 year. Further analysis
      subdivided patients into two groups based on initial LBP VAS scores. Results:
      Fifty-five percent of patients were females (n=65) and 45% males (n=54), with a
      mean age of 68.7 years and L4/5 being the level most frequently decompressed.
      Considering all surgeries, a statistically significant reduction in VAS back pain
      between pre-op and 6 weeks was seen (4.99 to 3.00, P<0.001). There was a
      significant (P<0.0001) average reductions in LBP by 1.66 units and leg pain by
      3.33 units after 1 year, with minimal difference between laminectomy and
      laminotomy. In the VAS back >=5 group, laminectomy patient's pain increased by
      0.63 units between 6 weeks and 1 year whilst laminotomy patients experienced a
      reduction in back pain of 0.51 units (P=0.063). ODI scores significantly improved
      for laminectomy and laminotomy by an average of 19.1%, 95% CI: 13.4-24.9% and
      10.8%, 95% CI: 5.8-15.7%, with no statistically significant difference between
      groups. Conclusions: No statistically significant differences were demonstrated
      between laminectomy and laminotomy outcomes, for LBP, leg pain or disability in
      our institute. On the basis of functional outcomes laminectomy remains a feasible
      approach in the treatment of lumbar spine stenosis. The data presented in this
      manuscript provides frequency data for subsequent comparative studies.

PMID- 29354736
TI  - Anterior lumbar interbody fusion (ALIF) as an option for recurrent disc
      herniations: a systematic review and meta-analysis.
AB  - Background: Recurrent intervertebral disc herniation is a relatively common
      occurrence after primary discectomy for lumbar intervertebral disc herniation.
      For recurrent herniations after repeat discectomies, a growing body of evidence
      suggests that fusion is effective in appropriately selected cases. Theoretically,
      anterior lumbar interbody fusion (ALIF) allows for comprehensive discectomy, less
      trauma to spinal nerves and paraspinal muscles and avoidance of the disadvantages
      of repeat posterior approaches. However, ALIF has also been associated with risk
      of vascular injury and retrograde ejaculation. This current systematic review and
      meta-analysis aims to assess the viability of ALIF as a surgical treatment for
      recurrent disc herniations. Methods: Seven studies were identified from six
      electronic databases and secondary reference lists. Pre-defined endpoints were
      extracted from the included studies and meta-analyzed. Results: For the 181
      patients from included studies, ALIF resulted in significant average improvements
      in Oswestry Disability Index (ODI) scores (50.49%, P<0.001), Visual Analogue
      Scale (VAS) back pain scores (47.85%, P<0.001) and VAS leg pain scores (37.00%,
      P<0.001). Average blood loss was acceptable at 122 mL (P<0.001) and average
      operation duration was 89 minutes (P<0.001). Average hospital stay was 5.28 days
      (P<0.001). Only 22 perioperative complications were reported, with subsidence the
      most commonly reported complication. Conclusions: Pooled evidence suggests that
      ALIF is a feasible approach for the treatment of recurrent disc herniations,
      demonstrating significant improvements in back and leg pain and minimal
      complications. These findings warrant further investigation in large prospective
      registries and multi-center studies.

PMID- 29354737
TI  - A radiographic follow-up study of stand-alone-cage and graft-plate constructs for
      single-level anterior cervical discectomy and fusion.
AB  - Background: Anterior cervical discectomy and fusion (ACDF) may be performed using
      an interbody cage or graft with an anterior plate or with a stand-alone (SA)
      interbody device without the anterior plate. The pros and cons of each vary. This
      study examined the radiographic outcome of the two techniques with a focus on
      implant subsidence. Methods: A retrospective review of cases of singe level ACDF
      by a single surgeon was undertaken. Medical and radiographic records were
      reviewed to determine subsidence, pre- and post-operative segmental and total
      lordosis in cohorts of both stand-alone and graft-and-plate constructs. Results:
      The post-operative radiographs of 35 patients with a SA cage were compared with
      41 patients with an allograft block and anterior plate (graft and plate; GP).
      There was no significant difference in overall subsidence between the two groups
      although there was a trend toward less clinically significant subsidence (2 mm)
      in the SA group. For single level ACDF, a SA device appears to be comparable in
      terms of undesired subsidence. Conclusions: Further studies with different
      implants and materials may offer further insight.

PMID- 29354738
TI  - Inpatient morbidity after spinal deformity surgery in patients with movement
      disorders.
AB  - Background: To investigate the inpatient perioperative morbidity rate of patients
      with movement disorders (MD) after spinal deformity surgery. Methods: The
      Nationwide Inpatient Sample database from 2002 to 2011 was queried to identify
      adult patients with MD who underwent spinal deformity surgery. Complication rates
      were compared between patients with MD and controls. A multiple logistic
      regression analysis was conducted to assess the effect of MD on outcome. Results:
      A total of 365 patients with MD (3.3%) were identified among 11,043 patients
      undergoing surgery for spinal deformity. Patients with MD were on average 8 years
      older than the control group (67 vs. 59 years of age, P<0.001). The complication
      rate was 55.1% for patients with MD and 43.7% for patients without MD (P<0.001).
      The most common complication was acute post-hemorrhagic anemia, which occurred in
      31.9% of all patients (41.6% in MD patients and 31.5% in the control group,
      P<0.001). Other complications that were more common in patients with MD included
      delirium (P<0.001), acute kidney injury (P=0.032), and pulmonary embolism
      (P=0.014). After controlling for patient age, sex, osteoporosis, complex
      procedures, fusion to the lumbosacral spine, use of bone morphogenetic protein,
      and use of blood transfusion, patients with MD were 1.3 times more likely to
      develop a complication compared to patients without MD [odds ratio (OR), 1.27;
      95% confidence interval (CI), 1.02-1.59; P=0.032] on multiple logistic regression
      analysis. No significant difference in hospital stay was observed. Conclusions:
      Patients with MD who undergo spinal deformity surgery may be at risk of higher
      rate of complications compared to patients without these disorders.

PMID- 29354739
TI  - Posterolateral thoracic decompression with anterior column cage reconstruction
      versus decompression alone for spinal metastases with cord compression: analysis
      of perioperative complications and outcomes.
AB  - Background: The optimal surgical strategy for patients with spinal metastases
      remains unknown. The aim of this study was to determine if performing an anterior
      column reconstruction to a posterolateral approach adds to perioperative
      complications. Methods: A retrospective review of all adult patients with spinal
      metastases who had a posterolateral approach for resection between January 2000
      and December 2008. Perioperative complications and functional outcomes were
      determined. Results: A total of 23 patients met the study criteria. Eleven
      patients underwent a costotransversectomy (CT) approach with anterior column
      reconstruction while 12 patients had a transpedicular (TP) approach without
      anterior column reconstruction. The mean age was 55.9 and 59.3 years in the CT
      and TP groups, respectively. There was no intraoperative death in either group.
      One death attributed to sepsis occurred in the TP group. A total of 5 (45.5%)
      complications occurred in the CT group and 7 (58.3%) in the TP group (P=0.68). An
      improvement in American Spinal Injury Association (ASIA) impairment scale grades
      was observed in 3 (27.3%) patients in the CT group and 1 (8.3%) in TP group. ASIA
      grades remained the same in 8 (72.7%) patients in CT and 10 (83.3%) patients in
      TP groups. No patient worsened in the CT group whereas 1 (8.3%) patient in TP
      group worsened. The median survival was 12.2 months in the CT group and 19.0
      months in the TP group (P=0.37). Conclusions: The addition of anterior column
      reconstruction does not appear to be associated with more operative or
      perioperative complications when compared to decompression alone. Anterior column
      reconstruction should not be aborted in fear of increasing perioperative
      complications.

PMID- 29354740
TI  - Long-term results with percutaneous interspinous process devices in the treatment
      of neurogenic intermittent claudication.
AB  - Background: Neurogenic intermittent claudication (NIC) is the main symptom of
      degenerative lumbar spinal stenosis. Percutaneous interspinous process
      decompression devices (IPDs) have been designed as an alternative therapy to
      conservative treatment and to open decompressive surgery for patients suffering
      from NIC. Initial short-term results were encouraging. We present the long-term
      results of a group of patients that we followed to provide insight on long-term
      outcomes and effectiveness of this technique compared to other decompression
      methods. Methods: Fifteen patients operated for NIC by implantation of
      percutaneous IPDs have been prospectively monitored for reoperations or
      complications. Follow-up (FU) was interrupted if the patient was reoperated.
      Results were considered poor if the patient had to be reoperated at any stage of
      the FU or if the treatment failed to alleviate the pain after 6 months. Results
      were considered average if the patient still suffered some pain but did not
      require reoperation. Results: The patients were followed up to 7 years after the
      initial surgery. The mean length of the FU was 3.53 years and all patients could
      be followed. At the end of the FU, the results were good in only 20.0% (3/15),
      average in 13.3% (2/15) and poor in 66.7% (10/15). Conclusions: Despite initial
      satisfactory results, long-term FU is disappointing, with 80% poor or average
      results. The long-term reoperation rate is high (66.6%), increases over time and
      is higher than after implantation of IPDs for decompression augmentation.
      Although this technique is simple and safe, its effectiveness seems short-lived.
      We recommend cautious use and informing patients about the risk of relatively
      early failure and recurrence.

PMID- 29354741
TI  - Identifying the superior and inferior gluteal arteries during a sacrectomy via a
      posterior approach.
AB  - Background: Identifying the gluteal vessels during a posterior sacrectomy can be
      challenging. This study defines anatomical landmarks that can be used to
      approximate the location of the superior and inferior gluteal arteries (SGA and
      IGA) during a posterior sacrectomy. Methods: Cadaveric dissection of six fresh
      adult pelvises to determine the location of the SGA and IGA in relation to the
      posterior-inferior aspect of the sacroiliac joint (PISIJ), lateral sacral margin
      and sacrococcygeal joint (SCJ). Results: The anatomical landmarks are easily
      palpable. The position of the SGA to the PISIJ is relatively constant as it is
      tethered by a posterior branch of the artery, which runs inferior to the PISIJ.
      The IGA position is also relatively constant below the mid-point of the PISIJ and
      SCJ. The vessels are separated from the sacrospinous/sacrotuberous ligament
      complex (SSTL) in the perisacral region and as a result an anatomical plane
      exists anterior to the SSTL, which affords protection of the vessels during SSTL
      transection. The distance between the vessels and the SSTL increases the more
      medial the dissection. Conclusions: The described anatomical landmarks can be
      used to predict the location of the SGA and IGA during posterior sacrectomy. An
      anatomical plane exists anterior to the SSTL, which provides protection to the
      vessels during SSTL transection. Furthermore, the distance between the vessels
      and the SSTL increases the more medial the dissection, thus, resection of the
      SSTL as close to the lateral sacral margin as the pathology permits, is
      advocated.

PMID- 29354742
TI  - Clinical experience and two-year follow-up with a one-piece viscoelastic cervical
      total disc replacement.
AB  - Background: The purpose of this study is to present clinical outcome data from a
      2-year post-market study of a viscoelastic one-piece cervical total disc
      replacement (TDR) in Europe. Methods: Thirty-nine patients were implanted at five
      surgical sites in an European post-market clinical study. Clinical outcomes
      included improvement of neck disability index (NDI) and visual analog scale
      scores for neck and arm pain from baseline to 2-year follow-up, neurological
      examinations, patients view on the success of surgery, complications, and
      subsequent surgical interventions. Results: Thirty patients had the Freedom(r)
      Cervical Disc (FCD) implanted at a single level, and nine patients were implanted
      at two adjacent levels. The population had a similar distribution of male [20]
      and female [19] subjects, with a mean age of 45 years. All self-administered
      outcome measures showed significant clinically important improvements from
      baseline to the 2-year follow-up. Mean preoperative NDI score improved from 48%
      to 20%, 13%, 8%, 6% and 4% at 6 weeks, 3, 6, 12, and 24 months, respectively.
      Average preoperative visual analog scale (VAS) scores of the neck, right and left
      arm pain intensity and frequency showed significant improvement. All neurological
      outcome measurements showed immediate improvement from preoperative values and
      continued improvement throughout 2 years follow-up. From pre-op to 24 months,
      neurological deficits declined in the population from 21% to 6% for reflex
      function, 62% to 17% for sensory function, and 38% to 3% for motor function. No
      patients experienced a deterioration in any measured outcomes compared with the
      preoperative situation. Patient satisfaction increased over 2 years post-op, with
      83% of patients responding that they would "definitely" choose to have the same
      treatment for their neck/arm condition and another 11% responding that they would
      "probably" choose to have the same treatment. Conclusions: The FCD performs as
      expected in patients with single-level and two-level degenerative disc disease.

PMID- 29354743
TI  - National outcomes following single-level cervical disc arthroplasty versus
      anterior cervical discectomy and fusion.
AB  - Background: To compare the differences in the thirty-day postoperative outcomes
      between cervical disc arthroplasty (CDA) and anterior cervical discectomy and
      fusion (ACDF). Methods: Patients undergoing primary single-level ACDF and CDA
      from 2010-2014 were identified by unique Current Procedural Terminology (CPT)
      codes within the American College of Surgeon's National Surgical Quality
      Improvement Program (NSQIP) database. Primary outcomes included surgical and
      medical complications, length of hospital stay (LOS), unplanned readmission,
      return to operating room, and mortality all occurring within 30 days of the
      initial procedure. Patients were propensity score-matched to reduce selection
      bias and differences in preoperative characteristics. Multivariate logistic
      regression models were utilized to determine associations between covariates and
      primary outcomes of interest. Results: Propensity score-matching produced a
      cohort of 1,305 patients with 652 (50.0%) ACDF and 653 (50.0%) CDA patients.
      There were no statistically significant differences in the development of major
      surgical or medical complications between the groups. ACDF patients experienced a
      significantly longer LOS (2.3+/-14.8 vs. 1.1+/-1.0 days, P=0.034) and unplanned
      hospital readmission (1.8% vs. 0.2%, P=0.002). For ACDF patients, increased LOS
      [odds ratios (OR), 4.21; 95% confidence interval (CI), 1.29-13.73; P=0.017] and
      increased readmission (OR, 12.17; 95% CI, 1.16-127.23; P=0.037) persisted in the
      multivariate model. Elevated ASA classification, preoperative anemia and elevated
      white blood cell count (WBC) were also associated with a significantly increased
      LOS. Conclusions: Although ACDF and CDA can be indicated for similar cervical
      pathologies, the latter can be performed safely and effectively with comparable
      perioperative risk of major complications. The increased readmission rate and LOS
      for patients undergoing ACDF may have significant impact on patient cost and
      outcomes.

PMID- 29354744
TI  - Three-dimensional reconstructions in spine and screw trajectory simulation on 3D
      digital images: a step by step approach by using Mimics software.
AB  - There is a rapidly increasing amount of literature outlining the use of three
      dimensional (3D) reconstruction and printing technologies in recent years.
      However, precise instructive articles which describe step-by-step methods of
      reconstructing 3D images from computed tomography (CT) or magnetic resonance
      imaging (MRI) remain limited. To address these issues, this article describes a
      detailed protocol which will allow the reader to easily perform the 3D
      reconstruction in their future research, to allow investigation of the
      appropriate surgical anatomy and allow innovative designs of novel screw fixation
      techniques or pre-operative surgical planning.

PMID- 29354745
TI  - Percutaneous screw placement in the lumbar spine with a modified guidance
      technique based on 3D CT navigation system.
AB  - Several guidance techniques have been employed to increase accuracy and reduce
      surgical time during percutaneous placement of pedicle screws (PS). The purpose
      of our study was to present a modified technique for percutaneous placement of
      lumbar PS that reduces surgical time. We reviewed 23 cases of percutaneous PS
      placement using our technique for minimally invasive lumbar surgeries and 24
      control cases where lumbar PS placement was done via common technique using
      Jamshidi needles (Becton, Dickinson and Company, Franklin Lakes, NJ, USA). An
      integrated computer-guided navigation system was used in all cases. In the
      technique modification, a handheld drill with a navigated guide was used to
      create the path for inserting guidewires through the pedicles and into the
      vertebral bodies. After drill removal, placement of the guidewires through the
      pedicles took place. The PS were implanted over the guidewires, through the
      pedicles and into the vertebral bodies. Intraoperative computed tomography was
      performed after screw placement to ensure optimal positioning in all cases. There
      were no intraoperative complications with either technique. PS placement was
      correct in all cases. The average time for each PS placement was 6.9 minutes for
      the modified technique and 9.2 minutes for the common technique. There was no
      significant difference in blood loss. In conclusion, this modified technique is
      efficient and contributes to reduced operative time.

PMID- 29354747
TI  - Systematic review of cortical bone trajectory versus pedicle screw techniques for
      lumbosacral spine fusion.
AB  - Fusion of the lumbosacral spine is a common surgical procedure to address a range
      of spinal pathologies. Fixation in lumbar fusion has traditionally been performed
      using pedicle screw (PS) augmentation. However, an alternative method of screw
      insertion via cortical bone trajectory (CBT) has been advocated as a less
      invasive approach which improves initial fixation and reduces neurovascular
      injury. There is a paucity of robust clinical evidence to support these claims,
      particularly in comparison to traditional pedicle screws. This study aims to
      review the available evidence to assess the merits of the CBT approach. Six
      electronic databases were searched for original published studies which compared
      CBT with traditional PS and their findings reviewed. Nine comparative studies
      were identified through a comprehensive literature search. Studies were
      classified as retrospective cohort, prospective cohort or case control studies
      with medium quality as assessed by the GRADE criteria. The available literature
      is not cohesive regarding outcomes and complications of CBT versus PT procedures.
      Most studies found no difference in operative time, but reported less blood loss
      during CBT. Radiological outcomes show no difference in slippage at one year
      although CBT is associated with greater bone-density compared to PT. Results for
      post-operative pain are inconclusive.

PMID- 29354748
TI  - Spondylolisthesis with spondylolysis in a 17-month-old: a case report.
AB  - Spondylolysis is frequently seen in adolescents, typically at the L5 vertebral
      level. While there may be a congenital predisposition for spondylolysis, it has
      long been suggested that the defect results from a fatigue or stress fracture of
      the pars interarticularis. Spondylolisthesis may result from a bilateral
      spondylolytic defect and is frequently asymptomatic. There is a paucity of
      literature on infant and toddler spondylolysis, as the focus is primarily on
      school-aged children, typically those over ten years of age. This case report
      presents an incidentally discovered L5 spondylolysis with spondylolisthesis in a
      17-month-old female. The patient presented to the emergency department with
      multiple facial abrasions and bruises from reportedly being struck by her 4-year
      old sister. Her past medical history included a hospitalization four months prior
      for a distal radius buckle fracture from a thirty foot fall from a window. A
      routine non-accidental trauma work-up was performed, including a skeletal survey
      which demonstrated L5 bilateral pars defect with Myerding grade 2
      spondylolisthesis. An MRI of the lumbar spine was performed, again demonstrating
      the L5 bilateral pars defect with position dependent reduction of the
      spondylolisthesis. The patient was seen back in the orthopedic office three
      months later which is her latest follow-up. Dynamic plain films of the lumbar
      spine were unchanged from previous imaging, without evidence of instability or
      slip progression. Further progression of her slip should warrant consideration
      for further treatment, whether it be cast immobilization or surgery.

PMID- 29354746
TI  - The genetic implication of scoliosis in osteogenesis imperfecta: a review.
AB  - Osteogenesis imperfecta (OI) is a kind of heritable connective tissue disorder,
      including blue sclerae, hearing loss, skeletal dysplasia causing bone fragility
      and deformities. It is typically caused by collagen related gene mutations, which
      could lead to bone formation abnormalities. Scoliosis is one of the most common
      and severe spinal phenotype which has been reported in approximately 26-74.5% of
      all OI patients. Recent breakthroughs have suggested that OI can be divided into
      more than 16 types based on genetic mutations with different degrees of
      scoliosis. In this review, we summarize the etiology of scoliosis in OI,
      especially the genetic studies of different types. We aim to provide a systematic
      review of the genetic etiology and clinical suggestions of scoliosis in OI.

PMID- 29354749
TI  - Focal hypermobility observed in cervical arthroplasty with Mobi-C.
AB  - In recent decades cervical arthroplasty, or cervical disc replacement, has been
      steadily increasing in popularity as a procedure for the treatment of
      degenerative pathologies of the cervical spine. This is based on an evolving body
      of literature that documents superior outcomes in cervical disc replacement over
      fusion, for both single and double level pathologies, in well selected patients.
      One of the more recent and popular implants currently on the market is the Mobi-C
      cervical artificial disc (LDR Medical; Troyes, France). In this paper we report
      on two cases where focal hypermobility was observed following total disc
      replacement using the Mobi-C cervical artificial disc. This is followed by a
      discussion as to potential contributing factors to this hypermobility in relation
      to both implant design, and operative technique, suggesting potential changes
      that might prevent this in future patients.

PMID- 29354750
TI  - Unusual cauda equina syndrome due to multifocal ependymoma infiltrated by
      lymphoma.
AB  - Myxopapillary ependymoma is a rare tumour of the central nervous system (CNS);
      this subtype of ependymoma occurs most frequently in cauda equina, conus
      medullaris or filum terminale. The treatment consists of complete removal of the
      tumour including its capsule when possible since it is usually a solitary lesion.
      Non-Hodgkin lymphoma of the CNS is found in only 1.3% of cauda equina tumours. We
      report the case of a 62-year-old man who presented to our institution with
      progressive weakness of his right lower extremity, with numbness and paresthesia
      of both feet. He was suffering from one month of right sciatica. Lumbosacral MRI
      displayed two intradural extramedullary lesions, the first one was located
      posteriorly to L1-L2 and the second one was spreading from L4 to S2 presenting as
      a mucoid cyst in its superior part with hyperintense T2 signal, isointense on T1
      weighted with high and homogeneous contrast enhancement in the inferior solid
      component. Imaging also found three additional intradural, extramedullary tumor
      formations with contrast enhancement, located respectively at C5-C6, C7 and T4. A
      L1-L2 and S1-S2 laminectomy was performed in emergency and total removal was
      achieved. Neuropathologist concluded that the tumor was a myxopapillary
      ependymoma infiltrated by large B-cell lymphoma. Although rare, this phenomenon
      (coexisting tumors within the same lesion) should be known by neurosurgeons
      because the occurrence of collision tumors affects the treatment and the
      patient's prognosis. In our case, two different types of tissue were mingled in
      the same location-this finding is very uncommon and has, to our knowledge, never
      been reported before.

PMID- 29354751
TI  - Scoliosis in Dandy-Walker syndrome: a case report and review of literature.
AB  - This submission presents a case of scoliosis in a patient with established Dandy
      Walker anomaly of the brain. A retrospective review of the patient's case notes
      was undertaken and the limited literature on this subject reviewed. The 13-year
      old girl presented with a stiff right thoracic scoliosis typical of adolescent
      idiopathic scoliosis. The scoliotic segment also presented with significant
      lordosis. She had facial and truncal dysmorphism characteristic of Dandy-Walker
      complex and her brain images confirmed the diagnosis. She underwent scoliosis
      surgery by the posterior approach uneventfully. In conclusion scoliosis is
      hitherto unreported in the Dandy-Walker complex. The results of intervention
      appear satisfactory.

PMID- 29354752
TI  - Primary leiomyosarcoma of the spine treated with total en bloc spondylectomy: the
      first case in Thailand-a case report and literature review.
AB  - Leiomyosarcoma is a rare type of malignant soft tissue tumor and also one of the
      most aggressive soft tissue sarcomas. It commonly occurs in uterus, abdominal
      viscera, retroperitoneal space and soft tissue of the extremities. Primary
      osseous leiomyosarcoma is a rare condition. Furthermore, primary leiomyosarcoma
      of the spine is extremely rare. Only few cases have been reported. However, the
      treatment and outcomes remains controversial. Therefore, the objective of this
      case report is to illustrate the management of this extremely rare disease by
      using total en bloc spondylectomy (TES) procedure, which is one of a suitable
      option for surgical resection of the spinal tumors. In this study, we presented
      an unusual case of a 61-year-old female, who was diagnosed as primary
      leiomyosarcoma of the twelfth thoracic spine with liver metastasis, treated with
      total en bloc spondylectomy of the twelfth thoracic vertebra followed by
      chemotherapy. On last follow-up, 6 months after the surgery, the clinical outcome
      remained in good condition and no signs of local recurrence. In conclusion,
      primary leiomyosarcoma of the spine is an extremely rare and difficult to
      diagnosis. Immunohistochemistry studies are very important for confirmation of
      the diagnosis. Standard treatment remains controversial. However, surgical
      resection is still treatment of choice. One of the most effective surgical
      options is TES, which give the better outcome and minimize local recurrence, if
      indicate.

PMID- 29354753
TI  - Unusual imaging presentation of spinal glomus tumor: case report.
AB  - A glomangioma, also known as a glomus tumor, is a benign lesion and had rare
      occurrence of spine region. In this study, we presented a spinal glomus tumor
      with an unusual radiological presentation, which is different from osteolytic
      intraosseous patterns illustrated before. A 26-year-old male with compressive
      myelopathy caused by epidural intraspinal lesion over T11 level. Radiological
      presentation revealed reactive sclerotic change over the body and lamina was
      found on the same level in computed tomography (CT) examination. Surgical
      resection was applied for en bloc tumor resection. The patient had well recovery
      after surgery. The pathology revealed cavernous haemangioma-like vascular
      structures, compatible with glomus tumor. Radiological diagnosis of spinal glomus
      tumor has limitation and difficulty preoperatively. Surgical intervention was
      suggested for patient with clinical neurological deficit and pathological
      approval.

PMID- 29354754
TI  - Spinal subdural hematoma post foramen magnum decompression-rare complication in a
      patient with rhomboencephalosynapsis.
AB  - Spinal subdural hematoma (SSDH) as a complication of posterior fossa surgery is
      extremely rare and can have potentially serious consequences. We report a case of
      delayed extensive SSHD presenting as cauda equina syndrome (CES) following
      foramen magnum decompression and occipito-cervical (OC) fusion.

PMID- 29354755
TI  - Forestier syndrome presenting with dysphagia: case report of a rare presentation.
AB  - Diffuse idiopathic skeletal hyperostosis (DISH) (Forestier syndrome) is a
      rheumatologic disease, the etiology of which is not exactly known. It is
      characterized by spinal osteophyte formations resulting from the ossification of
      the paravertebral ligaments and muscles. Anterior longitudinal ligament is the
      usual site of involvement and the frequency of the disease increases after the
      5th decade. Lower cervical segments are the most frequently involved regions
      whereas the upper cervical involvement leading to dysphagia is very rare. In this
      report, a 77-year-old patient with Forestier syndrome in upper cervical region
      presenting with dysphagia was presented. Anterior cervical osteophyte resection
      was performed with no need for discectomy, fusion or stabilization. The patient
      showed a significant improvement in his all preoperative symptoms, and no
      recurrence was detected at 1-year follow-up.

PMID- 29354756
TI  - Multifocal intradural extramedullary anaplastic ependymoma of the spine.
AB  - Ependymomas are neuroectodermal tumours arising from the ependymal lining of the
      ventricles and central canal of the spinal cord. Intradural extramedullary (IDEM)
      ependymomas which are multifocal, and/or anaplastic (WHO grade III) at
      presentation are exceedingly rare. We present the second case of multifocal
      anaplastic IDEM ependymoma in the literature. A 47-year old female presented with
      left gluteal and thigh pain radiating to the groin associated with paraesthesiae.
      She had a normal neurological examination. Magnetic resonance imaging of the
      lumbar spine and subsequent magnetic resonance imaging (MRI) of the remaining
      neuroaxis demonstrated >10 lesions throughout cervical, thoracic and lumbosacral
      levels. There were no intracranial lesions. The patient initially underwent
      surgery for removal of three symptomatic lesions at S2. She recovered well. One
      year later she had further surgery for three progressing lesions at T5. Four of
      six lesions were WHO grade III. Two smaller nodules at T5 were WHO grade II. The
      patient had mild sensory disturbance over the right side of the trunk which
      resolved postoperatively. There were no long-term sequelae. The patient
      subsequently underwent full craniospinal irradiation using proton beam therapy.
      Due to their rarity, there are no guidelines for the management of multifocal
      IDEM ependymoma. The only previously published case of multifocal anaplastic IDEM
      ependymoma by Schuurmans et al. involved surgical resection and 20 cycles of
      whole-spine radiotherapy. Schuurmans patient unfortunately died two years post
      diagnosis with progressive cranial metastases and post-radiation myelopathy. In
      our case, all remaining lesions are stable and she is neurologically intact at 48
      month follow up.

PMID- 29354757
TI  - Obstructed spinopelvic fixation in the setting of a triangular titanium
      sacroiliac fusion implant: a case description.
AB  - Achieving lumbosacral fusion through spinopelvic fixation is an important and
      challenging aspect of spinal deformity surgery. Numerous instrumentation
      techniques are available, with iliac screws and S2-alar-iliac (SRAI) screws being
      most commonly used today. However, the increasing popularity of minimally
      invasive sacroiliac (SI) fusion as a common procedure performed for SI joint pain
      presents a distinct challenge in complex adult deformity cases requiring iliac
      screw fixation. We report a case of a 71-year-old female with a longstanding
      history of spinal deformity status-post T11-L5 fusion and a subsequent right
      sided SI joint fusion who presented with sagittal imbalance. The SI joint fusion
      implant obstructed the pathway for spinopelvic fixation. Spinopelvic fixation was
      achieved by burring a pathway through the SI joint implant. The increasing
      popularity of minimally invasive SI fusion as a common procedure performed for SI
      joint pain presents a distinct challenge in complex adult deformity cases
      requiring iliac screw fixation. This is the first report in the literature
      describing a technique for spinopelvic fixation in the setting of screw
      obstruction due to an instrumented SI joint.

PMID- 29354758
TI  - Gibbus deformity after non-tuberculosis osteomyelitis.
AB  - Gibbus deformities are characterized by anterior collapse of one or more
      vertebral bodies resulting in kyphosis. These deformities usually arise from
      spinal infections, and are traditionally associated with tuberculosis; other
      pathogens are rarely reported in the literature. In this case report, the authors
      describe a patient with a sharp, angulated Gibbus deformity presenting with back
      pain and myelopathy. The patient was placed on antibiotics, underwent T11-T12
      corpectomy, placement of an expandable cage, and T8-L3 fusion with improvement of
      symptoms. Microbiology returned positive for non-tuberculosis osteomyelitis, and
      the postoperative course was uneventful. This report further reviews the
      presentation, pathology, development, and neurosurgical treatment of Gibbus
      deformities. Although they have become rare as rates of tuberculosis have
      declined, Gibbus deformities remain an important surgical entity that should be
      recognized by the spine surgeon.

PMID- 29354759
TI  - A rare cause of late onset neurological deficit in post tuberculous kyphotic
      deformity-case report.
AB  - Late onset neurological deficit is a rare complication of spinal tuberculosis.
      Reactivation of the disease and compression by internal gibbus are the common
      causes for late onset neurological deficit. We report a rare cause of late onset
      paraplegia in a patient with post tubercular kyphotic deformity. The late onset
      neurological deficit was due to the adjacent segment degeneration proximal to the
      kyphotic deformity. Posterior hypertrophied ligamentum flavum and anterior disc
      osteophyte complex caused the cord compression. The increased stress for
      prolonged period at the end of the deformity was the reason for the accelerated
      degeneration. Patient underwent posterior decompression, posterolateral and
      interbody fusion. Deformity correction was not done. To our best knowledge, this
      is only the second report of this unusual cause of late onset paraplegia.

PMID- 29354760
TI  - Survival impact of the number of lymph node retrieved on patients with node
      negative gastric cancer: more is better?

PMID- 29354761
TI  - Surgical treatment of gastrointestinal stromal tumors of the stomach: current
      status and future perspective.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of
      the gastrointestinal tract, with the majority found in the stomach. Surgical
      resection of the primary gastric GISTs with complete resection margin has been
      the forefront of curative treatment. The indications for surgical resection are
      usually related to symptomatic gastric GISTs at presentation. Primary gastric
      GISTs resection performed conventionally through an open surgery can now be
      frequently achieved by minimal invasive surgery with similar oncological outcome.
      Surgeon's selection of the type of surgical techniques such as open, laparoscopic
      and endoscopic resections depends on the site, size and local invasion of gastric
      GISTs to the adjacent organ. Similarly those factors dictate the extent of
      gastric resections in the form of wedge, partial or total gastrectomy. All these
      inherent tumor factors (size and mitotic index), patient factors (older age,
      male) and surgical factors (incomplete resection margin, tumor rupture or
      spillage) play an important role in stratifying the malignant potential risk of
      primary gastric GISTs and their chances of recurrence. The understanding of gene
      mutation driving the growth of GISTs and the discovery of tyrosine kinase
      inhibitors (TKIs) has altered the surgical management of advanced and metastatic
      GISTs. Multi-modal therapy incorporating the surgical resection of GISTs and
      utilizing the molecular targeted therapy in the adjuvant, neoadjuvant and
      palliative settings can offer optimal personalized outcome and prolong patient's
      overall survival (OS).

PMID- 29354762
TI  - Surgery of the pancreatic cystic echinococcosis: systematic review.
AB  - The prevalence of pancreatic cystic echinococcosis (PCE) in the world is low
      ranging between 0.2% and 0.6%. The diagnosis of PCE is easy when it is associated
      to other location such as liver, it became difficult when PCE was isolated
      simulating other diagnosis such as pseudocyst, a choledochal cyst, serous or
      mucinous cystadenoma and cystadenocarcinoma. This systematic review aimed to
      provide evidence-based answer to the following questions: (I) what are the
      efficient tools to affirm the diagnosis of isolated PCE and (II) what are the
      best therapeutic strategy for the PCE? An electronic search was performed by two
      authors (W Dougaz, I Bouasker). Medline, Scopus, Embase, Web of Science, Google
      Scholar and Cochrane collaboration were consulted. The keywords used were "cyst",
      "echinococcosis", "hydatid cyst" and "pancreas". All abstracts were analyzed
      followed by extraction of the full text by the same two authors (W Dougaz, I
      Bouasker), all divergences were resolved by discussion with C Dziri.
      Recommendations were based on Oxford's classification: (I) what are the efficient
      tools to affirm the diagnosis of PCE? -ultrasound remains the cornerstone of
      diagnosis. Magnetic resonance imaging (MRI) reproduces the ultrasound defined
      features of CE better than computed tomography (CT). MRI with heavily T2-weighted
      series is preferable to CT. Pancreatic duct MRI should be promising to identify a
      fistula between PCE and pancreatic duct (level of evidence 3-recommendation B);
      (II) what are the best therapeutic strategy for the PCE? -surgery is the main
      treatment of PCE. Open approach is validated. The decision depends of the
      location of PCE: head versus body and/or tail of the pancreas (level of evidence
      5-recommendation D): for the head of the pancreas, the tendency is toward
      conservative surgery. For body and/or tail of the pancreas, the tendency is
      toward radical surgery. Medical treatment (albendazole) should be prescribed 1
      week before surgery and 2 months during postoperative period (level II evidence
      and grade C recommendation).

PMID- 29354764
TI  - Modifications in the International Study Group for Pancreatic Surgery (ISGPS)
      definition of postoperative pancreatic fistula.
AB  - Postoperative pancreatic fistula (POPF) remains the major postoperative cause of
      morbidity and mortality following pancreatic surgery. Since 2005, the
      International Study Group of Pancreatic Fistula (ISGPF) definition and
      classification has been adopted worldwide allowing the comparison among different
      surgical approaches and mitigation strategies. Over the last 11 years, several
      limitations have emerged from clinical practice and in 2016 the International
      Study Group for Pancreatic Surgery (ISGPS) updated the POPF definition and
      grading system. Objectives of this review article were to summarize modifications
      in the updated ISGPS definition and to illustrate their clinical impact.

PMID- 29354763
TI  - Downstaging for hepatocellular cancer: harm or benefit?
AB  - : Downstaging of hepatocellular carcinoma (HCC) to enable liver transplantation
      has become an area of intense interest and research. It may allow a curative
      option in patients outside widely accepted transplantation criteria, with
      outcomes that, in some studies, are comparable to transplantation for patients
      within criteria. There have been conflicting opinions on the best downstaging
      protocols, criteria for downstaging eligibility and for assessment of response.
      We therefore aimed to review the literature and evidence for downstaging, as well
      as considering its drawbacks. CONCLUSION: Pooled analyses have suggested success
      in down staging in about half of patients treated, but with higher recurrence
      rates than patients initially within transplantation criteria. Studies with
      strict inclusion criteria and mandatory waiting time before transplantation
      reported survival equivalent to patients who did not require downstaging. In
      carefully selected patients, there is a role for down staging to provide the
      chance of transplantation and cure, with acceptable outcomes. Further multi
      center, well-designed studies are required to clarify who will mostly benefit.
      Until such data is available, downstaging criteria should be stated within
      transplantation programs and relevant decisions should be discussed by
      multidisciplinary teams.

PMID- 29354765
TI  - Minimally invasive surgery for gastric gastrointestinal stromal tumors.
AB  - Minimally invasive surgery has been increasingly performed for gastric
      gastrointestinal stromal tumors (GIST). In this review we discuss and summarize
      the current evidence on minimally invasive surgery for gastric GISTs.
      Laparoscopic resection for gastric GIST has been consistently shown to be
      associated with superior perioperative outcomes with no compromise in oncological
      outcomes when compared to open resection in numerous retrospective case-control
      studies. It has also been shown to be safe and feasible for large tumors or
      tumors located in unfavorable sites. However, to date, there remains a lack of
      level 1 evidence from prospective randomized control trials in support of
      laparoscopic resection.

PMID- 29354767
TI  - Impact of direct-acting antiviral agents on the risk for hepatocellular
      carcinoma.

PMID- 29354766
TI  - Laparoscopic management of neuroendocrine tumors: state-of-the-art.
AB  - Over recent years, minimally invasive pancreatic resections have increasingly
      been reported in the literature. Even though pancreatic surgery is still
      considered a challenge for surgeons due to its technical difficulties and high
      morbidity, the consolidation of minimally invasive pancreatic surgery has
      included the treatment of pancreatic neuroendocrine tumors (PNETs). This article
      presents a systematic review of the literature with regards to the laparoscopic
      treatment of PNETs in order to assess the safety and feasibility of laparoscopic
      pancreatic resections.

PMID- 29354768
TI  - Acute-on-chronic liver failure-old concepts made clearer.

PMID- 29354769
TI  - Predicting fatalities in serious idiosyncratic drug-induced liver injury-a matter
      of choosing the best Hy's law.

PMID- 29354770
TI  - Therapeutic drug monitoring in inflammatory bowel disease: too little too early?
      comments on the American Gastroenterology Association Guideline.

PMID- 29354771
TI  - Mortality associated with drug-induced liver injury (DILI).

PMID- 29354773
TI  - Rare gastrointestinal stromal tumors (GIST): omentum and retroperitoneum.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms
      that arise in the gastrointestinal tract and rarely elsewhere in the abdomen.
      GISTs that develop outside the digestive tract are called extra-GISTs (EGISTs).
      The incidence of EGISTs is reported to be approximately 10% of all GISTs, and the
      median age is younger than that of conventional GISTs. EGISTs have similar
      histology and immunohistochemical features as conventional GISTs, with the
      majority of them in the omentum and mesentery. Most GISTs harbor a kinase
      activating mutation in either KIT or PDGFRA. For EGISTs, the incidence of this
      type of mutation is 40-50%, which is somewhat lower than for conventional GISTs.
      EGISTs may have a worse prognosis compared with conventional GISTs with high
      mitotic indices, large size, and distant metastasis including lymph node
      involvement. In large abdominal tumors, the visceral origin is almost impossible
      to discern.

PMID- 29354772
TI  - Endoscopic resection of gastric gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in
      the gastrointestinal tract, and about 60% of them are found in the stomach. With
      the widespread application of endoscopy and endoscopic ultrasonography (EUS),
      more and more gastric GISTs are being found in an early stage (with a relative
      small diameter and no metastasis), giving the chance of complete resection.
      Endoscopic resection such as endoscopic band ligation (EBL), endoscopic
      submucosal dissection (ESD), endoscopic submucosal excavation (ESE), endoscopic
      full-thickness resection (EFTR) and submucosal tunneling endoscopic resection
      (STER), is a minimally invasive method compared with the conventional surgical
      approaches (open or laparoscopic), and has been demonstrated to be safe and
      effective for treating gastric GISTs. This review summarizes the recent advances
      on endoscopic resection of gastric GISTs, aiming to provide a rational management
      strategy for gastric GISTs.

PMID- 29354774
TI  - In vitro antifungal activity of essential oils extracted from plants against
      fluconazole-susceptible and -resistant Candida albicans.
AB  - Background and Purpose: Candidaalbicans is the most common cause of candidal
      infections. Various studies have shown drug resistance among C. albicans
      isolates; thus, it is necessary to discover replacement treatments for Candida
      infections. In this study, we aimed to compare the effects of different essential
      oils against azoles-resistant and azoles-susceptible isolates. Materials and
      Methods: Twenty fluconazole-resistant and 20 susceptible C. albicans isolates
      obtained from oral, vaginal, and cutaneous tissues of patients with candidiasis
      were evaluated. The efficacy and minimum inhibitory concentrations (MICs) of
      Zataria multiflora, Geranium herbarum,Lavendula officinalis,Cuminum,
      cyminum,Allium heamanthoides, and Artemisia sieberi essential oils against C.
      albicans were determined on the basis of a reference method for broth
      microdilution susceptibility testing of yeasts as suggested by Clinical and
      Laboratory Standards Institute (CLSI, M27-S4). After inoculation, incubation, and
      subculturation, the MICs were determined through comparison with the control.
      Results: The obtained MICs for Zataria multiflora, Geranium herbarum, Artemisia
      sieberi, Allium heamanthoides, Cumminum cyminum, and Lavendula officinalis were
      0.1-0.25 ul/ml (mean: 0.155 ul/ml), 0.625-1.66 ul/ml (mean: 0.93 ul/ml) 0.833-2.0
      ul/ml (mean: 1.21 ul/ml), 0.1-0.25 ul/ml (mean: 0.155 ul/ml), 2-4 ul/ml (mean:
      3.1 ul/ml), and 1.5-3.0 ul/ml (mean: 2.4 ul/ml), respectively. The results showed
      that Zataria multiflora and Allium heamanthoides essential oils were more
      efficient than other essential oils against Candida species. There were no
      significant differences between various Candida strains in terms of
      susceptibility to the essential oils. In addition, there were no significant
      differences in the MICs of these essential oils against the azoles-resistant and
      azoles-susceptible isolates. Conclusion: In this study, the anti-Candida effects
      of six essential oils against both azoles-resistant and azoles-susceptible
      isolates were similar. Given the documented resistance of different Candida
      species to synthetic and chemical antifungals, these essential oils are effective
      replacement treatments for cutaneous and mucosal Candida infections, especially
      in resistant or recurrent cases.

PMID- 29354775
TI  - In vitro antimicrobial effect of different root canal sealers against oral
      pathogens.
AB  - Background and Purpose: Root canal therapy is the primary method for the
      treatment of an infected pulp in modern dentistry. The main aim of endodontic
      treatment is the elimination of bacteria and their products from infected root
      canals. In this study, we attempted to investigate the antimicrobial activity of
      three root canal sealers against oral pathogens. Materials and Methods: The
      antimicrobial effectiveness of three endodontic sealers with different chemical
      compositions, namely resin (AH 26), zinc oxide eugenol (ZOE), and mineral
      trioxide aggregate (MTA), against Candida albicans, Streptococcus sanguis,
      Streptococcus salivarius, Streptococcus mutans, and Lactobacillus casei was
      assayed by agar well diffusion method (AWDM). The tested sealers were prepared
      according to the manufacturer's instructions and poured in the prepared wells of
      agar plates; diluted inocula (105 and 106 CFU/ml) of the tested microorganism
      strains were also used. The minimum inhibitory concentration (MIC) values of the
      selected canal sealers ranged between 3.12 and 50 mg.ml-1 against the employed
      microorganism strains. All the plates were incubated at 37 degrees C under
      anaerobic condition for bacteria and at 30 degrees C for C. albicans. After three
      days, the inhibition zones were measured. Results: In this investigation, AH 26
      exhibited strong activity against C. albicans with the minimum inhibitory
      concentration of 12.5 mg.ml-1, but ZOE and MTA did not act against C. albicans.
      ZOE sealer had the highest antimicrobial activity against the tested bacteria,
      while MTA showed the lowest antimicrobial activity. Conclusion: The ascending
      sequence of microbial growth inhibition zones was as follows AH 26 > ZOE > MTA.

PMID- 29354776
TI  - Isolation of keratinophilic fungi from the soil of Greater Tunb, Abu-Musa, and
      Sirri islands in the Persian Gulf, Iran.
AB  - Background and Purpose: Keratinophilic fungi are among the important groups of
      fungi living in the soil. This study aimed to isolate and identify keratinophilic
      fungi from the soil of three Iranian islands, namely Greater Tunb, Abu Musa, and
      Sirri, located in the Persian Gulf using morphological and molecular (polymerase
      chain reaction) methods. Materials and Methods: In this study, a total of 60 soil
      samples were collected from the three islands of Greater Tunb, Abu Musa, and
      Sirri. The samples were analyzed for the presence of the keratinophilic fungi
      using a hair baiting technique. Furthermore, the identification of keratinophilic
      fungi was accomplished through the employment of molecular and sequencing
      techniques. Results: A total of 130 fungal isolates, including 11 genera with 24
      species, were collected. Accordingly, Chrysosporium tropicum (24;18.5%), C.
      keratinophilum (17; 13.1%), Chrysosporium species (15; 11.5%), Aspergillus
      species ( 8;6.1%), Aspergillus flavus (8; 6.1%), Penicillium species (8;6.1%),
      Alternaria spp ( 6; 4.6%), Phoma species (5; 3.8%), Aphanoascus verrucosus
      (4;3.1%), Fusarium chlamydosporum (4; 3.1%), Aspergillustrreus (4;3.1%),
      Acremonium species (4; 3.1%), and other fungi( 23; 17.8 %) isolates were
      identified . All isolates of keratinophilic fungi were isolated from the soils
      with the pH range of 7-9. Conclusion: The results of this study contributed
      towards a better conceptualization of the incidence pattern of keratinophilic
      fungi in the regions of Iran. Given that no study has investigated this issue,
      the findings of the present study can be beneficial for the management of public
      health surveillance, physicians, and epidemiologists.

PMID- 29354777
TI  - Isolation and molecular characterization of Cryptococcus species isolated from
      pigeon nests and Eucalyptus trees.
AB  - Background and Purpose: Cryptococcus species are pathogenic and non-pathogenic
      basidiomycete yeasts that are found widely in the environment. Based on
      phenotypic methods, this genus has many species; however, its taxonomy is
      presently being re-evaluated by modern techniques. The Cryptococcus species
      complex includes two sibling taxa of Cryptococcus neoformans and Cryptococcus
      gattii. We aimed to investigate the possible distribution of Cryptococcus species
      in pigeon nests and Eucalyptus trees in Ilam, Iran, using molecular techniques.
      Materials and Methods: Two hundred and seventy-four specimens were collected from
      pigeon nests and Eucalyptus trees during 2016-2017. All the specimens were sub
      cultured on Sabouraud Glucose Agar with chloramphenicol and bird seed agar. For
      molecular identification, the ITS15.8SITS2 rDNA region was amplified using the
      first and fourth internal transcribed spacer (ITS1 and ITS4, respectively)
      primers. The purified products were applied for cycle sequencing reactions in
      forward direction with ITS1 primer. The obtained results were analyzed with
      Chromas 2.3. Results: Thirty-three out of 186 cultures (17.7%) and 11 out of 88
      cultures (12.5%) were positive among pigeon nest and Eucalyptus tree specimens,
      respectively. Cryptococcus albidus (17.2%), C. albidus var. kuetzingii (3.4%), C.
      adeliensis (3.4%), C. uzbekistanensis (3.4%), and C. neoformans var. grubii
      (3.4%) were isolated from pigeon nests, and Cryptococcusadeliensis (25%) was the
      only Cryptococcus species isolated from Eucalyptus trees. Conclusion: The
      presence of pigeons and Eucalyptus trees in the vicinity of some particular
      places such as rest homes and hospitals should be considered as a risk factor for
      the immunocompromised population.

PMID- 29354778
TI  - The efficacy of gaseous ozone against different forms of Candida albicans.
AB  - Background and Purpose: Ozone is an inorganic molecule with effective
      antimicrobial properties. Clinical treatment of ozonated water was used for the
      elimination of Candidaalbicans, Enterococcus faecalis, endotoxins, and biofilms
      from root canals. In addition, its therapeutic effects for tinea pedis, ulcers,
      and leishmaniasis were investigated. The purpose of the present study was to
      evaluate the fungicidal effects of ozone on different forms of C. albicans. In
      addition, antifungal susceptibility profile of strains was assessed before and
      after exposure to ozone. Materials and Methods: Fifty strains of C. albicans were
      exposed to gaseous ozone at different times. Furthermore, biofilm formation and
      germ tube production were evaluated when yeast suspensions were exposed to ozone.
      In addition, antifungal susceptibility of ozone resistant colonies was
      investiagted as compared to controls. Results: Ozone was highly effective in
      killing C.albicans in yeast form and inhibition of germ tube formation during 210
      and 180 s, respectively. Although with increasing exposure time biofilm
      production was considerably decreased, resistance to ozone was much higher among
      vaginal and nail isolates even after 60 min. All the strains were sensitive to
      fluconazole, caspofungin, and terbinafine pre- and post-ozone exposure.
      Resistance to amphotericin B was significantly enhanced after exposure to ozone.
      Conclusion: Although ozone was highly effective on the yeast form of C.albicans
      and it can inhibit the formation of germ tubes in C.albicans, the complete
      removal of biofilms did not happen even after 60 min. It seems that ozone therapy
      induces resistance to amphotericin B.

PMID- 29354779
TI  - First case of superficial infection due to Naganishia albida (formerly
      Cryptococcus albidus) in Iran: A review of the literature.
AB  - Background and Purpose: Naganishia albida (formerly Cryptococcus albidus) is a
      non-neoformans cryptococcal species rarely isolated as a human pathogen. Case
      report: Herein, we present the case of a 26-year-old Iranian man with a
      superficial cutaneous lesion in the axilla. The initial treatment for pityriasis
      versicolor by clotrimazole was unsuccessful. We performed skin sampling based on
      the standard protocol and conducted further investigations by the conventional
      laboratory tests and molecular analysis of the skin samples. All the mentioned
      analyses revealed N.albida as the causative agent of infection. The minimum
      inhibitory concentration (MIC) analysis was carried out for the isolated agent,
      and the patient was treated using 100 mg daily of oral itraconazole. Conclusion:
      N. albida can be the causative agent of some superficial infections. This is the
      first report on the successful detection and treatment of a superficial skin
      infection due to N. albida by oral itraconazole.

PMID- 29354780
TI  - Risk of Obstructive Sleep Apnoea is Associated with Glycaemia Status in South
      Asian Men and Women in the United States.
AB  - Aims: To examine the association between glycaemia status and the risk for
      obstructive sleep apnoea (OSA) in a cohort of South Asians living in the United
      States. Methods: A secondary analysis of a community based cohort of 899
      participants from the Mediators of Atherosclerosis in South Asians Living in
      America (MASALA) study. The Berlin Questionnaire was used to screen for OSA.
      Results: Almost one in four (24%) South Asians was at high risk for OSA. Compared
      to the normal glucose tolerance group (18%), high risk of OSA was significantly
      more likely in the prediabetes (24%) and diabetes (32%) groups (p = .007). More
      men (28%) than women (18%) were at high risk of OSA. Risk for OSA was also
      associated with higher haemoglobin A1c values, hypertension, large waist
      circumference, and BMI > 27.5 kg/m2. In a multivariate regression analysis, sleep
      disordered breathing (SDB) remained significantly associated with higher
      haemoglobin A1c values, even after controlling for waist circumference and other
      demographic and clinical factors. Conclusions: The risk for SDB and OSA was high
      among South Asian men and women. Given the association between dysglycaemia and
      risk for OSA, these health issues require simultaneous clinical assessment.
      Future studies using objective sleep measures such as polysomnography are
      warranted in the diagnosis and treatment of OSA in the South Asian adult
      population already at high risk for dysglycaemia.

PMID- 29354781
TI  - Suppression of Arrhythmia by Enhancing Mitochondrial Ca2+ Uptake in
      Catecholaminergic Ventricular Tachycardia Models.
AB  - Cardiovascular disease-related deaths frequently arise from arrhythmias, but
      treatment options are limited due to perilous side effects of commonly used
      antiarrhythmic drugs. Cardiac rhythmicity strongly depends on cardiomyocyte Ca2+
      handling and prevalent cardiac diseases are causally associated with
      perturbations in intracellular Ca2+ handling. Therefore, intracellular Ca2+
      transporters are lead candidate structures for novel and safer antiarrhythmic
      therapies. Mitochondria and mitochondrial Ca2+ transport proteins are important
      regulators of cardiac Ca2+ handling. Here we evaluated the potential of
      pharmacological activation of mitochondrial Ca2+ uptake for the treatment of
      cardiac arrhythmia. To this aim,we tested substances that enhance mitochondrial
      Ca2+ uptake for their ability to suppress arrhythmia in a murine model for
      ryanodine receptor 2 (RyR2)-mediated catecholaminergic polymorphic ventricular
      tachycardia (CPVT) in vitro and in vivo and in induced pluripotent stem cell
      derived cardiomyocytes from a CPVT patient. In freshly isolated cardiomyocytes of
      RyR2R4496C/WT mice efsevin, a synthetic agonist of the voltage-dependent anion
      channel 2 (VDAC2) in the outer mitochondrial membrane, prevented the formation of
      diastolic Ca2+ waves and spontaneous action potentials. The antiarrhythmic effect
      of efsevin was abolished by blockade of the mitochondrial Ca2+ uniporter (MCU),
      but could be reproduced using the natural MCU activator kaempferol. Both
      mitochondrial Ca2+ uptake enhancers (MiCUps), efsevin and kaempferol,
      significantly reduced episodes of stress-induced ventricular tachycardia in
      RyR2R4496C/WT mice in vivo and abolished diastolic, arrhythmogenic Ca2+ events in
      human iPSC-derived cardiomyocytes.

PMID- 29354782
TI  - Immune Response to Koi Herpesvirus (KHV) of Koi and Koi * Red Common Carp
      (Cyprinus carpio).
AB  - Koi herpesvirus (KHV), also known as Cyprinid herpes virus 3 (Cyprinid 3) is
      lethal disease in common carp and koi (Cyprinus carpio). Two different groups (KK
      and RK) were infected KHV by intraperitoneal injection. Fish for gene expression
      analysis were sampled at 0 h, 12 h, 24 h, 48 h and 72 h post infection (p.i). The
      results showed that two immune related gene, Interferons (INFs) alphabeta and
      Interleukin (IL)-12 p35 induced a high response in RK. The IL-12 p35 cytokine and
      Toll-like receptor (TLR) 9 were significantly high expressed on 48 h post
      infection (p.i) in RK as compared to the KK. The histopatological examination
      reveals focal necrosis in liver and infiltrate of lymphocytes in spleen of KK as
      compared to the RK. In immunohistochemistry analysis, the KHV protein high
      expressed in the infected kidney cell and slenocyte of KK. Therefore, the
      expression of IL-12 p35, IFN alphabeta and TLR 9 may provide a potentially genes
      related with KHV resistance in Koi and red common carp * koi.

PMID- 29354783
TI  - Expression Analysis of Interferon-Stimulated Gene 15 in the Rock Bream
      Oplegnathus fasciatus against Rock Bream Iridovirus (RSIV) Challenge.
AB  - Interferon-stimulated gene 15 (ISG15) is known to interfere with viral
      replication and infection by limiting the viral infection of cells. Interferon
      stimulated gene 15 (ISG15) interferes with viral replication and infectivity by
      limiting viral infection in cells. It also plays an important role in the immune
      response. In this study, tissue-specific expression of ISG15 in healthy rock
      bream samples and spatial and temporal expression analysis of rock bream ISG15
      (RbISG15) were performed following rock bream iridovirus (RSIV) infection.
      RbISG15 expression was significantly higher in the eye, gill, intestine, kidney,
      liver, muscle, spleen, and stomach, but low in the brain. There were particularly
      high levels of expression in the liver and muscle. RbISG15 expression was also
      examined in several tissues and at various times following RSIV infection. ISG15
      expression increased within 3 h in the whole body and decreased at 24 h after
      infection. In addition, temporal expression of several tissues following RSIV
      infection showed a similar pattern in the muscle, kidney, and spleen, increasing
      at 3 h and decreasing at 72 h. These results suggest that ISG15 plays an
      important role in the immune response of rock bream. Overall, this study
      characterizes the response of RbISG15 following RSIV infection.

PMID- 29354784
TI  - Aberrant Expression of Cx Isoforms in the Adult Caput Epididymis exposed to
      Estradiol Benzoate or Flutamide at the Weaning.
AB  - Connexin (Cx) involves in the regulation of various physiological functions of
      tissue by forming a channel, a gap junction which allows direct cell-cell
      communication, between adjacent cells. The effect of a single subcutaneous
      treatment of estradiol benzoate (EB) or flutamide (Flu) at the weaning age on the
      expression of Cx isoforms in the adult caput epididymis was evaluated in this
      research. Using quantitative real-time PCR analysis, a low-dose of EB [0.015
      MUg/kg body weight (BW)] caused significant decreases of Cx30.3, Cx32, Cx40,
      Cx43, and Cx45 mRNA levels and no change of Cx26, Cx31, Cx31.1, Cx37 transcript
      levels. The treatment of a high-dose EB (1.5 MUg/kg BW) resulted in reduced
      expression of Cx30.3, Cx31, Cx43, and Cx45 but increased expression of Cx37 and
      Cx40. Expression of all Cx isoforms examined, except Cx31, was significantly
      increased by the treatment of a low-dose Flu (500 MUg/kg BW). However, the
      treatment of a high-dose Flu (5 mg/kg BW) led significant expressional
      suppression of Cx30.3, Cx31, Cx31.1, Cx32, Cx40, Cx43, and Cx45 but an increase
      of Cx37 transcript level. With the comparison of previous findings, the
      expression of Cx isoforms in the adult epididymis after the exposure to EB or Flu
      is likely differentially regulated in regional-specific and/or exposed postnatal
      age-specific manner.

PMID- 29354785
TI  - Correlation of Developmental Deformity with Calcium, Phosphorus, or Estradiol
      17beta Levels in Reared Red Spotted Grouper, Epinephelus akaara Juveniles.
AB  - Skeletal deformities are significant problems that affect the growth and
      commercial value of fish reared in hatcheries. However, studies of bone metabolic
      process related to skeletal deformities are limited. We investigated the
      potential correlation between bone deformities and plasma calcium, phosphorus,
      and estradiol-17beta levels in reared red spotted grouper (Epinephelus akaara)
      juveniles. We collected E. akaara frys from private farms at 110, 140, 180 and
      300 days after hatching (DAH), and classified the normal and deformed fish by
      observing their external shape and inner frame by soft X-ray. We also analyzed
      the calcium, phosphorous, and estradiol-17beta levels in their plasma. A
      comparison between normal and deformed fish, indicated that calcium and estradiol
      17beta levels were higher in deformed fish than in the normal at 180 and 300 DAH.
      The level of phosphorus was also higher in deformed individuals than in normal
      fish, but only at 300 DAH. These results suggest that skeletal deformities are
      associated with increases in plasma calcium, phosphorus, and estradiol-17beta
      levels.

PMID- 29354786
TI  - Regulation of the Endoplasmic Reticulum Stress by BIP/GRP78 is involved in
      Meiotic Maturation of Porcine Oocytes In Vitro.
AB  - In the present study, we investigated the role of binding immunoglobulin
      protein/glucose-regulated protein, 78-kDa (BIP/GRP78)-regulated endoplasmic
      reticulum (ER)-stress on meiotic maturation and cumulus cells expansion in
      porcine cumulus-oocyte complexes (COCs). Previously, it has been demonstrated
      that unfolded protein response (UPR)-related genes, such as molecules involved in
      ER-stress defense mechanisms, were expressed in matured oocytes and cumulus cells
      during in vitro maturation (IVM) of porcine oocytes. However, BIP/GRP78-mediated
      regulation of ER stress in porcine oocytes has not been reported. Firstly, we
      observed the effects of knockdown of BIP/GRP78 (an UPR initiation marker) using
      porcine-specific siRNAs (#909, #693, and #1570) on oocyte maturation. Among all
      siRNAs, siRNA #693 significantly reduced the protein levels of UPR marker
      proteins (BIP/GRP78, ATF4, and P90ATF6) in porcine COCs observed by Western
      blotting and immunofluorescence analysis. We also observed that the reduction of
      BIP/GRP78 levels by siRNA#693 significantly inhibited the meiotic maturation of
      oocytes (siRNA #693: 32.5+/-10.1% vs control: 77.8+/-5.3%). In addition, we also
      checked the effect of ER-stress inhibitors, tauroursodeoxycholic acid (TUDCA, 200
      MUM) and melatonin (0.1 MUM), in BIP/ GRP78-knockdown oocytes. TUDCA and
      melatonin treatment could restore the expression levels of ER-stress marker
      proteins (BIP/GRP78, p-eIF2alpha, eIF2alpha, ATF4, and P90ATF6) in siRNA #693
      transfected matured COCs. In conclusion, these results demonstrated that
      BIP/GRP78-mediated regulation of UPR signaling and ER stress plays an important
      role in in vitro maturation of porcine oocytes.

PMID- 29354787
TI  - Mitochondrial Complex I Inhibition Accelerates Amyloid Toxicity.
AB  - Alzheimer's disease (AD) is neurodegenerative disease, characterized by the
      progressive decline of memory, cognitive functions, and changes in personality.
      The major pathological features in postmortem brains are neurofibrillary tangles
      and amyloid beta (Abeta) deposits. The majority of AD cases are sporadic and age
      related. Although AD pathogenesis has not been established, aging and declining
      mitochondrial function has been associated. Mitochondrial dysfunction has been
      observed in AD patients' brains and AD mice models, and the mice with a genetic
      defect in mitochondrial complex I showed enhanced Abeta level in vivo. To
      elucidate the role of mitochondrial complex I in AD, we used SH-SY5Y cells
      transfected with DNA constructs expressing human amyloid precursor protein (APP)
      or human Swedish APP mutant (APP-swe). The expression of APP-swe increased the
      level of Abeta protein in comparison with control. When complex I was inhibited
      by rotenone, the increase of ROS level was remarkably higher in the cells
      overexpressing APP-swe compared to control. The number of dead cell was
      significantly increased in APP-swe-expressing cells by complex I inhibition. We
      suggest that complex I dysfunction accelerate amyloid toxicity and mitochondrial
      complex I dysfunction in aging may contribute to the pathogenesis of sporadic AD.

PMID- 29354788
TI  - Genetic Distances of Scallop (Chlamys farreri) Populations investigated by PCR
      Procedure.
AB  - The author performed PCR-based genetic platform to measure the hierarchical
      dendrogram of Euclidean genetic distances of Korean scallop populations (KSP),
      particularly for Chlamys farreri, which was further compared with those of the
      Chinese scallop populations (CSP), by employing the with specifically designed
      oligonucleotide primer sets. The scallop is economically and ecologically very
      important bivalves in South Korea. Relatively, individuals of KSP population were
      fairly distantly related to that of CSP population, as shown in the hierarchical
      dendrogram of Euclidean genetic distances. Comparatively, individuals of KSP
      population were fairly distantly related to that of CSP population. Thus analysis
      of genetic difference between scallop populations could provide important
      statistics for fishery and aquaculture. Overall the results showed specific
      and/or conserved genetic loci between scallop populations. Information on the
      genetic distance of the bivalve would be helpful to understand scallop expansion
      or conservation in the coastal regions of South Korea. Specific markers developed
      by the author will be useful for the analysis of scallop population genetics and
      distribution in coastal region.

PMID- 29354790
TI  - Protein Interaction Mapping of Translational Regulators Affecting Expression of
      the Critical Stem Cell Factor Nos.
AB  - The germline stem cells of the Drosophila ovary continuously produce eggs
      throughout the life- span. Intricate regulation of stemness and differentiation
      is critical to this continuous production. The translational regulator Nos is an
      intrinsic factor that is required for maintenance of stemness in germline stem
      cells. Nos expression is reduced in differentiating cells at the post
      transcriptional level by diverse translational regulators. However, molecular
      mechanisms underlying Nos repression are not completely understood. Through three
      distinct protein-protein interaction experiments, we identified specific
      molecular interactions between translational regulators involved in Nos
      repression. Our findings suggest a model in which protein complexes assemble on
      the 3' untranslated region of Nos mRNA in order to regulate Nos expression at the
      post-transcriptional level.

PMID- 29354789
TI  - Hershberger Assays for Bisphenol-A and Its Substitute Candidates.
AB  - Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects
      including reduced fertility, reproductive tract abnormalities, metabolic
      disorder, cancer induction, neurotoxicity and immunotoxicity. In the present
      study, we conducted Hershberger assay to evaluate whether the two candidates to
      replace BPA have androgenic or antiandrogenic activity. The assay was carried out
      using immature castrated Sprague-Dawley male rats. After 7 days of the surgery,
      testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40
      mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by
      subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were
      BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied,
      and then the weights of five androgen-dependent tissues [ventral prostate,
      seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's
      glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen
      and liver) were measured. All test materials including BPA did not exhibit any
      androgenic activity in the assay. On the contrary, antiandrogen-like activities
      were found in all test groups, and the order of the intensity was CHDM > BPA >
      ISO in the five androgen-sensitive tissues. There was no statistical difference
      between low dose treatment and high dose treatment of BPA group as well as ISO
      group. In CHDM group, high dose treatment exhibited most severe weight reduction
      in all measured tissues. There was no statistical difference in androgen
      insensitive tissue measurements, except BPA groups. Since the effects of ISO
      treatment on the accessory sex organs were much less or not present at all when
      compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM
      treatment brought most severe weight reduction in all of androgen-sensitive
      tissues, so this material should be excluded for further screening of BPA
      substitute selection.

PMID- 29354791
TI  - Cathepsin B & D and the Survival of Early Embryos in Red Spotted Grouper,
      Ephinephelus akaara.
AB  - Survival of embryos largely depends on yolk processing during early development.
      Proteolytic enzymes, cathepsin B & D (ctsb & ctsd) are known to have some
      important roles in yolk processing of various fish species. Mature female red
      spotted groupers were injected with human chorionic gonadotropin (HCG) to induce
      ovulation. The fertilized eggs and embryos were sampled at 0, 4 and 24 HPF (hours
      post fertilization). Survivals of each groups of embryos were checked at 24 and
      48 HPH (hours post hatching). Transcripts of ctsb & ctsd showed the highest level
      at 0 HPF and relatively high at 4 HPF, but greatly decreased at 24 HPF. In bad
      egg quality group (BE, embryos survived until 24 HPH), transcript level of ctsb
      at 4 HPF were significantly lower than the transcript level at the same stage in
      good egg quality group (GE, embryos survived until 48 HPH) while no significant
      change of ctsb transcript level was observed at 0 or 24 HPF between BE and GE.
      Transcript level of ctsd was decreased at 24 HPF, but the difference was not as
      strong as the case of ctsb transcript. These results suggest that maternal ctsb
      transcript rather than ctsd transcript is likely to be involved in egg quality
      resulting in the difference of survival rate of embryos at early developmental
      period in this species.

PMID- 29354792
TI  - Mitochondria-Specific Monoclonal Antibodies in Eggs and Embryos of the Ascidian
      Halocynthia roretzi.
AB  - Ascidian embryos have become an important model for embryological studies,
      offering a simple example for mechanisms of cytoplasmic components segregation.
      It is a well-known example that the asymmetric segregation of mitochondria into
      muscle lineage cells occurs during ascidian embryogenesis. However, it is still
      unclear which signaling pathway is involved in this process. To obtain molecular
      markers for studying mechanisms involved in the asymmetric distribution of
      mitochondria, we have produced monoclonal antibodies, Mito-1, Mito-2 and Mito-3,
      that specifically recognize mitochondriarich cytoplasm in cells of the ascidian
      Halocynthia roretzi embryos. These antibodies stained cytoplasm like reticular
      structure in epidermis cells, except for nuclei, at the early tailbud stage.
      Similar pattern was observed in vital staining of mitochondria with DiOC2, a
      fluorescent probe of mitochondria. Immunostaining with these antibodies showed
      that mitochondria are evenly distributed in the animal hemisphere blastomeres at
      cleavage stages, whereas not in the vegetal hemisphere blastomeres. Mitochondria
      were transferred to the presumptive muscle and nerve cord lineage cells of the
      marginal zone in the vegetal hemisphere more than to the presumptive mesenchyme,
      notochord and endoderm lineage of the central zone. Therefore, it is suggested
      that these antibodies will be useful markers for studying mechanisms involved in
      the polarized distribution of mitochondria during ascidian embryogenesis.

PMID- 29354793
TI  - Erratum to : Bitter Melon Seed Extract does not Alter Photoperiodic Effects on
      Reproduction of Male Golden Hamsters.
AB  - [This corrects the article DOI: 10.12717/DR.2017.21.2.215.].

PMID- 29354794
TI  - Electrically driven spin qubit based on valley mixing.
AB  - The electrical control of single spin qubits based on semiconductor quantum dots
      is of great interest for scalable quantum computing since electric fields provide
      an alternative mechanism for qubit control compared with magnetic fields and can
      also be easier to produce. Here we outline the mechanism for a drastic
      enhancement in the electrically-driven spin rotation frequency for silicon
      quantum dot qubits in the presence of a step at a heterointerface. The
      enhancement is due to the strong coupling between the ground and excited states
      which occurs when the electron wave function overcomes the potential barrier
      induced by the interface step. We theoretically calculate single qubit gate times
      tpi of 170 ns for a quantum dot confined at a silicon/silicon-dioxide interface.
      The engineering of such steps could be used to achieve fast electrical rotation
      and entanglement of spin qubits despite the weak spin-orbit coupling in silicon.

PMID- 29354795
TI  - Application of a faith-based integration tool to assess mental and physical
      health interventions.
AB  - Background: To build on current research involving faith-based interventions
      (FBIs) for addressing mental and physical health, this study a) reviewed the
      extent to which relevant publications integrate faith concepts with health and b)
      initiated analysis of the degree of FBI integration with intervention outcomes.
      Methods: Derived from a systematic search of articles published between 2007 and
      2017, 36 studies were assessed with a Faith-Based Integration Assessment Tool
      (FIAT) to quantify faith-health integration. Basic statistical procedures were
      employed to determine the association of faith-based integration with
      intervention outcomes. Results: The assessed studies possessed (on average)
      moderate, inconsistent integration because of poor use of faith measures, and
      moderate, inconsistent use of faith practices. Analysis procedures for
      determining the effect of FBI integration on intervention outcomes were
      inadequate for formulating practical conclusions. Conclusions: Regardless of
      integration, interventions were associated with beneficial outcomes. To determine
      the link between FBI integration and intervention outcomes, additional analyses
      are needed.

PMID- 29354796
TI  - DNA Methylation-Based Classifier for Accurate Molecular Diagnosis of Bone
      Sarcomas.
AB  - Purpose: Pediatric sarcomas provide a unique diagnostic challenge. There is
      considerable morphologic overlap between entities, increasing the importance of
      molecular studies in the diagnosis, treatment, and identification of therapeutic
      targets. We developed and validated a genome-wide DNA methylation based
      classifier to differentiate between osteosarcoma, Ewing's sarcoma, and synovial
      sarcoma. Materials and Methods: DNA methylation status of 482,421 CpG sites in 10
      Ewing's sarcoma, 11 synovial sarcoma, and 15 osteosarcoma samples were determined
      using the Illumina Infinium HumanMethylation450 array. We developed a random
      forest classifier trained from the 400 most differentially methylated CpG sites
      within the training set of 36 sarcoma samples. This classifier was validated on
      data drawn from The Cancer Genome Atlas (TCGA) synovial sarcoma, TARGET
      Osteosarcoma, and a recently published series of Ewing's sarcoma. Results:
      Methylation profiling revealed three distinct patterns, each enriched with a
      single sarcoma subtype. Within the validation cohorts, all samples from TCGA were
      accurately classified as synovial sarcoma (10/10, sensitivity and specificity
      100%), all but one sample from TARGET-OS were classified as osteosarcoma (85/86,
      sensitivity 98%, specificity 100%) and 14/15 Ewing's sarcoma samples classified
      correctly (sensitivity 93%, specificity 100%). The single misclassified
      osteosarcoma sample demonstrated high EWSR1 and ETV1 expression on RNA-seq
      although no fusion was found on manual curation of the transcript sequence. Two
      additional clinical samples, that were difficult to classify by morphology and
      molecular methods, were classified as osteosarcoma when previously suspected to
      be a synovial sarcoma and Ewing's sarcoma on initial diagnosis, respectively.
      Conclusion: Osteosarcoma, synovial sarcoma, and Ewing's sarcoma have distinct
      epigenetic profiles. Our validated methylation-based classifier can be used to
      provide diagnostic assistance when histological and standard techniques are
      inconclusive.

PMID- 29354797
TI  - Correlates of plasma and platelet tissue factor pathway inhibitor, factor V, and
      Protein S.
AB  - Background: Plasma Tissue Factor Pathway Inhibitor (TFPI) circulates bound to
      factor V (fV) and Protein S (PS). Estrogen therapy decreases plasma TFPI and PS.
      TFPI, fV, and PS circulate within platelets, and are released upon activation to
      modulate thrombus formation. Objective: Identify factors affecting the
      concentrations of plasma and platelet TFPI, fV, and PS. Methods: Blood samples
      were obtained from 435 healthy individuals. Plasma total TFPI, TFPIalpha, fV, and
      PS, and platelet TFPI, fV, and PS were quantified. Correlations between these
      protein concentrations and age, gender, race, and estrogen use were established.
      Results: In males, only plasma fV increased with age, while in females, all
      plasma analytes increased with age. Males had higher plasma total TFPI,
      TFPIalpha, and PS than females. The platelet proteins in either sex remained
      relatively stable with increasing age. Platelet TFPI and PS were comparable in
      both sexes, while platelet fV was higher in females. Estrogen use was associated
      with decreased plasma total TFPI and TFPIalpha, and platelet PS, but not with
      platelet TFPI concentration. Racial differences in plasma and platelet proteins
      were observed, some of which were larger than inter-individual differences
      observed within racial groups. TFPI, fV and PS concentrations correlated in
      plasma, while only fV and PS correlated in platelets. Conclusions: Plasma and
      platelet TFPI, fV and PS differ in their: (i) in vivo association; (ii)
      demographic correlates; and (iii) alteration by estrogen therapies. Therefore,
      the plasma and platelet pools of these proteins may modulate hemostasis and
      thrombosis via different biochemical pathways.

PMID- 29354798
TI  - Activity of Factor XII-Locarno.
AB  - Background: Factor XII (FXII) Locarno is a natural variant with proline replacing
      Arg353 at the activation cleavage site, preventing conversion to the fully active
      protease factor XIIa (FXIIa). Recently, we showed that FXII restricted to a
      single chain form (sc-FXII) by replacing Arg353 with alanine expresses
      proteolytic activity that is enhanced by cofactors such as polyphosphate. Aim: To
      determine if the Pro353 substitution affects the activity of sc-FXII. Methods:
      Wild type FXII (FXII-WT), FXII-R353A, and FXII Locarno (FXII-R353P) were tested
      for their abilities to activate prekallikrein, and to induce thrombin generation
      and coagulation in plasma in a factor XI-dependent manner. Results: FXII-WT is
      converted to FXIIa by autoactivation in the presence of polyphosphate, and by
      incubation with kallikrein. FXII-R353P and FXII-R353A were not converted to FXIIa
      by these methods. Despite this, FXII-R353A converts prekallikrein to kallikrein,
      and the reaction is enhanced by polyphosphate. FXII-R353P also converts
      prekallikrein to kallikrein, but at a slower rate than FXII-R353A. In FXII
      deficient plasma induced to clot with silica, FXII-R353A is a better promoter of
      factor XI-dependent thrombin generation and coagulation than FXII-R353P.
      Conclusion: The activity of sc-FXII is sensitive to perturbations in the
      activation loop, which contains residue 353. Homology modeling based on the
      crystal structure of the FXII homolog tissue plasminogen activator suggests that
      Pro353 introduces changes in the shape and flexibility of the activation loop
      that disrupt key interactions that support an active conformation in sc-FXII.

PMID- 29354799
TI  - Temperature dependent 29Si incorporation during deposition of highly enriched
      28Si films.
AB  - In this study, we examine the mechanisms leading to 29Si incorporation into
      highly enriched 28Si films deposited by hyperthermal ion beams at elevated
      temperatures in the dilute presence of natural abundance silane (SiH4) gas.
      Enriched 28Si is a critical material in the development of quantum information
      devices because 28Si is free of nuclear spins that cause decoherence in a quantum
      system. We deposit epitaxial thin films of 28Si enriched in situ beyond 99.99998
      % 28Si onto Si(100) using an ion beam deposition system and seek to develop the
      ability to systematically vary the enrichment and measure the impact on quantum
      coherence. We use secondary ion mass spectrometry to measure the residual 29Si
      isotope fraction in enriched samples deposited from ~ 250  degrees C up to 800 
      degrees C. The 29Si isotope fraction is found to increase from < 1 * 10-6 at the
      lower temperatures, up to > 4 * 10-6 at around 800  degrees C. From these data,
      we estimate the temperature dependence of the incorporation fraction, s, of SiH4,
      which increases sharply from about 2.9 * 10-4 at 500  degrees C to 2.3 * 10-2 at
      800  degrees C. We determine an activation energy of 1.00(8) eV associated with
      the abrupt increase in incorporation and conclude that below 500  degrees C, a
      temperature independent mechanism such as activation from ion collisions with
      adsorbed SiH4 molecules is the primary incorporation mechanism. Direct
      incorporation from the adsorbed state is found to be minimal.

PMID- 29354800
TI  - Halting Schistosoma haematobium - associated bladder cancer.
AB  - Background: At present schistosomiasis is endemic in 78 countries affecting more
      than 260 million people. Schistosomiasis haematobia alone affects more than 112
      millions. Material and Methods: We performed a computerized search of Pubmed
      database with keywords: bladder cancer cost and schistosomiasis mass treatment.
      Results: Bladder cancer is an important sequelae of this infection. In low
      resource countries, where this disease is endemic, individuals inflicted with
      bladder cancer have very limited access to treatment and death is most probably
      certain. Conclusion: Mass treatment with praziquantel is an easy, safe and
      inexpensive treatment that could save the lives of thousands and reduce the
      morbidity of millions.

PMID- 29354801
TI  - IL-27p28 Production by XCR1+ Dendritic Cells and Monocytes Effectively Predicts
      Adjuvant-Elicited CD8+ T Cell Responses.
AB  - It is well accepted that the innate response is a necessary prerequisite to the
      formation of the adaptive response. This is true for T cell responses against
      infections or adjuvanted subunit vaccination. However, specific innate parameters
      with predictive value for the magnitude of an adjuvant-elicited T cell response
      have yet to be identified. We previously reported how T cell responses induced by
      subunit vaccination were dependent on the cytokine IL-27. These findings were
      unexpected, given that T cell responses to an infection typically increase in the
      absence of IL-27. Using a novel IL-27p28-eGFP reporter mouse, we now show that
      the degree to which an adjuvant induces IL-27p28 production from dendritic cells
      and monocytes directly predicts the magnitude of the T cell response elicited. To
      our knowledge, these data are the first to identify a concrete innate correlate
      of vaccine-elicited cellular immunity, and they have significant practical and
      mechanistic implications for subunit vaccine biology.

PMID- 29354802
TI  - Intracranial artery stenosis: Current status of evaluation and treatment in
      China.
AB  - Intracranial artery stenosis (ICAS), a common cause of ischemic stroke, is a
      growing cause of concern in China. Recently, many epidemiological, etiological,
      pathophysiological, therapy, and diagnostic imaging studies have focused on ICAS,
      and guidelines and consensus on the diagnosis and treatment of ICAS have been
      published and updated by domestic experts. Such work is pivotal to our enhanced
      comprehension, diagnosis, and treatment of ICAS. In this review, we summarize the
      latest progress in the evaluation and treatment of ICAS in China.

PMID- 29354803
TI  - Current advances in circulating inflammatory biomarkers in atherosclerosis and
      related cardio-cerebrovascular diseases.
AB  - Atherosclerosis (AS) is a systemic chronic disease affecting both the coronary
      and cerebral arteries. Inflammation plays a key role in the initiation and
      progression of AS, and numerous inflammatory factors have been proposed as
      potential biomarkers. This article reviews recent research in studies on major
      circulating inflammatory biomarkers to identify surrogates that may reflect
      processes associated with AS development and the risk of AS-related vascular
      events, such as Von Willebrand factor, lectin-like oxidized low-density
      lipoprotein receptor-1, soluble urokinase plasminogen activator receptor,
      regulated upon activation, normal T-cell expressed and secreted, and
      microparticles, which may provide new perspectives for clinical AS evaluation and
      risk stratification.

PMID- 29354804
TI  - Are statins beneficial for the treatment of pulmonary hypertension?
AB  - Pulmonary hypertension (PH) is a condition characterized by vasoconstriction and
      vascular remodeling with a poor prognosis. The current medical treatments
      available are supportive care therapy and pulmonary vascular-targeted therapy.
      Targeted treatments for PH include prostacyclin analogs, endothelin receptor
      antagonists, and phosphodiesterase type 5 inhibitors; however, these treatments
      cannot reverse pulmonary vascular remodeling. Recently, many novel treatment
      options involving drugs such as statins have been emerging. In this review, we
      attempt to summarize the current knowledge of the role of statins in PH treatment
      and their potential clinical effects. Many basic researches have proved that
      statins can be helpful for the treatment of PH both in vitro and in experimental
      models. The main mechanisms underlying the effects of statins are restoration of
      endothelial function, attenuation of pulmonary vascular remodeling, regulation of
      gene expression, regulation of intracellular signaling processes involved in PH,
      anti-inflammatory responses, and synergy with other targeted drugs. Nevertheless,
      clinical researches, especially randomized controlled trials for PH are rare. The
      current clinical researches show contrasting results on the clinical effects of
      statins in patients with PH. Carefully designed randomized, controlled trials are
      needed to test the safety and efficacy of statins for PH treatment.

PMID- 29354805
TI  - Current progress and outcomes of clinical trials on using epidermal growth factor
      receptor-tyrosine kinase inhibitor therapy in non-small cell lung cancer patients
      with brain metastases.
AB  - Non-small cell lung cancer (NSCLC) continues to be one of the major causes of
      cancer-related deaths worldwide, and brain metastases are the major cause of
      death in NSCLC patients. With recent advances in understanding the underlying
      molecular mechanism of NSCLC development and progression, mutations in epidermal
      growth factor receptor (EGFR) have been recognized as a key predictor of
      therapeutic sensitivity to EGFR tyrosine kinase inhibitors (TKIs). Using EGFR-TKI
      alone or in combination with standard treatments such as whole-brain radiotherapy
      and surgery has been an effective strategy for the management of brain
      metastasis. Particularly, a newer generation of EGFR-TKIs, including osimertinib
      and AZD3759, has been developed. These new EGFR-TKIs can cross the blood-brain
      barrier and potentially treat EGFR-TKI resistance and improve prognosis. In this
      article, current progress and outcomes of clinical trials on the use of EGFR-TKIs
      for treating NSCLC patients with brain metastasis will be reviewed.

PMID- 29354806
TI  - Ethnic differences in the association between angiotensin-converting enzyme gene
      insertion/deletion polymorphism and peripheral vascular disease: A meta-analysis.
AB  - Background: Several studies have investigated the association of angiotensin
      converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with
      peripheral vascular disease (PVD); however, the results remain controversial.
      Therefore, we conducted the current meta-analysis to evaluate this relationship
      in the general population of different ethnicities. Methods: We searched PubMed,
      Embase, Web of Science, Wanfang Database, and CNKI to identify eligible studies.
      Random-effect models were applied to estimate the pooled odds ratio (OR) with a
      95% confidence interval (CI), regardless of between-study heterogeneity. Results:
      A total of 13 studies with 1966 cases and 6129 controls were included in this
      meta-analysis. The pooled ORs for the association between ACE I/D polymorphism
      and PVD risk were not statistically significant in the overall population under
      all genetic models. In further ethnicity-stratified analyses, we found a
      statistically significant association of ACE I/D polymorphism with PVD
      susceptibility in Asians under most models. However, the association among
      Caucasians did not reach statistical significance. Conclusion: ACE I/D
      polymorphism might be associated with susceptibility to PVD in the Asian
      population, but there was no clear evidence indicating a similar significant
      relationship among Caucasians.

PMID- 29354808
TI  - Correlation between the clinicopathological features and prognosis in patients
      with extranodal natural killer/T cell lymphoma.
AB  - Objective: To investigate the correlation between the clinicopathological
      features and prognosis in patients with extranodal natural killer (NK)/T-cell
      lymphoma (ENKTCL). Methods: One hundred and four patients diagnosed with ENKTCL
      at the Department of Pathology, Cancer Hospital, Chinese Academy of Medical
      Sciences, Beijing, China from November 1991 to September 2011 were included in
      the study. The clinicopathological features and their correlations with disease
      prognosis were evaluated in these patients. Results: The number of effective
      follow-up cases was 56 (53.8%) by the end of last follow-up in October 2015.
      Univariate survival analysis showed that granzyme B, perforin, and Bcl-2
      expression was significantly associated with a poor prognosis in ENKTCL (P =
      0.033, 0.004, and 0.034, respectively), whereas platelet-derived growth factor
      receptor-alpha (PDGFRA) expression was significantly associated with a better
      prognosis (P = 0.034). Ki-67 overexpression (>=50%) was significantly associated
      with a poor prognosis (P = 0.017). Different treatment approaches were also
      associated with prognosis (P = 0.014); specifically, the efficacies of
      combination treatments including chemotherapy and radiotherapy, and autologous
      hematopoietic stem cell transplantation were significantly better than those
      involving radiotherapy and chemotherapy alone. Patient gender, age, tumor
      location, staging, the presence of B symptoms, pretreatment lactate dehydrogenase
      levels, and beta2-microglobulin levels were not associated with the prognosis of
      ENKTCL (P > 0.05). However, multivariate analyses showed that the treatment
      approach and all the immune markers were not independent prognostic factors for
      ENKTCL. Conclusion: Granzyme B, perforin, and Bcl-2 expression and Ki-67
      overexpression (>=50%) might be adverse prognostic factors for ENKTCL, whereas
      PDGFRA-positivity suggested a better disease prognosis. In addition, different
      treatment approaches might be closely related to patient prognosis.

PMID- 29354809
TI  - Acute myocardial infarction caused by myocardial bridging alone confirmed by
      using intravascular ultrasonography.

PMID- 29354807
TI  - Main air pollutants and ventricular arrhythmias in patients with implantable
      cardioverter-defibrillators: A systematic review and meta-analysis.
AB  - Objective: Previous studies of ambient air pollutants and ventricular arrhythmias
      in patients with implantable cardioverter-defibrillator (ICD) have yielded mixed
      results, and the association between air pollution and ventricular arrhythmias in
      these patients remains unclear. This study aimed to assess and quantify the
      association between exposure to major air pollutants [CO, inhalable particles
      (PM10), SO2, fine particulate matter (PM2.5), O3, and NO2] and the presence of
      ventricular arrhythmia in patients with ICD. Methods: The Medline, PubMed, Web of
      Science, Global Health Library, Virtual Health Library, Population Information
      Online (POPLINE), and New York Academy of Medicine Grey Literature Report
      databases were searched to identify studies analyzing the association between
      ventricular arrhythmias in patients with ICD and the abovementioned main air
      pollutants. Pooled estimates were generated using a random-effects model or fixed
      effects model, according to the value of heterogeneity. Heterogeneity within
      studies was assessed using Cochran's Q and I2 statistics. Funnel plots, Egger's
      regression test, and Begg's rank correlation method were used to evaluate
      publication bias. Sensitivity analyses were also conducted to evaluate the
      potential sources of heterogeneity. Results: After a detailed screening of 167
      studies, seven separate studies were identified. Ventricular arrhythmias in
      patients with ICD were found to be positively, but not significantly, associated
      with CO, PM10, SO2, PM2.5, and NO2, with a pooled estimate [odds ratio (OR)
      associated with each 10 MUg/m3 increase in pollutant concentration, except for
      CO, which was associated with each 1 mg/m3 increase in concentration] of 1.03
      [95% confidence interval (CI): 0.92-1.17, P = 0.59] for CO, 1.01 (95%CI: 0.97
      1.05, P = 0.55) for PM10, 1.09 (95%CI: 0.95-1.24, P = 0.22) for SO2, 1.07 (95%CI:
      0.95-1.21, P = 0.25) for PM2.5, and 1.06 (95%CI: 0.98-1.14, P = 0.16) for NO2. No
      increased risk of ventricular arrhythmias in patients with ICD was found to be
      associated with O3 (OR = 1.00; 95%CI: 0.98-1.01, P = 0.56). Conclusions: The
      results of this study provide little evidence that ambient air pollutants affect
      the risk of ICD discharges for treating ventricular arrhythmias.

PMID- 29354810
TI  - ShapeShop: Towards Understanding Deep Learning Representations via Interactive
      Experimentation.
AB  - Deep learning is the driving force behind many recent technologies; however, deep
      neural networks are often viewed as "black-boxes" due to their internal
      complexity that is hard to understand. Little research focuses on helping people
      explore and understand the relationship between a user's data and the learned
      representations in deep learning models. We present our ongoing work, ShapeShop,
      an interactive system for visualizing and understanding what semantics a neural
      network model has learned. Built using standard web technologies, ShapeShop
      allows users to experiment with and compare deep learning models to help explore
      the robustness of image classifiers.

PMID- 29354811
TI  - Unsupervised Discovery of Spatially-Informed Lung Texture Patterns for Pulmonary
      Emphysema: The MESA COPD Study.
AB  - Unsupervised discovery of pulmonary emphysema subtypes offers the potential for
      new definitions of emphysema on lung computed tomography (CT) that go beyond the
      standard subtypes identified on autopsy. Emphysema subtypes can be defined on CT
      as a variety of textures with certain spatial prevalence. However, most existing
      approaches for learning emphysema subtypes on CT are limited to texture features,
      which are sub-optimal due to the lack of spatial information. In this work, we
      exploit a standardized spatial mapping of the lung and propose a novel framework
      for combining spatial and texture information to discover spatially-informed lung
      texture patterns (sLTPs). Our spatial mapping is demonstrated to be a powerful
      tool to study emphysema spatial locations over different populations. The
      discovered sLTPs are shown to have high reproducibility, ability to encode
      standard emphysema subtypes, and significant associations with clinical
      characteristics.

PMID- 29354812
TI  - mHealth Visual Discovery Dashboard.
AB  - We present Discovery Dashboard, a visual analytics system for exploring large
      volumes of time series data from mobile medical field studies. Discovery
      Dashboard offers interactive exploration tools and a data mining motif discovery
      algorithm to help researchers formulate hypotheses, discover trends and patterns,
      and ultimately gain a deeper understanding of their data. Discovery Dashboard
      emphasizes user freedom and flexibility during the data exploration process and
      enables researchers to do things previously challenging or impossible to do - in
      the web-browser and in real time. We demonstrate our system visualizing data from
      a mobile sensor study conducted at the University of Minnesota that included 52
      participants who were trying to quit smoking.

PMID- 29354813
TI  - A quantitative approach for pesticide analysis in grape juice by direct
      interfacing of a matrix compatible SPME phase to dielectric barrier discharge
      ionization-mass spectrometry.
AB  - We evaluated the performance of a dielectric barrier discharge ionization (DBDI)
      source for pesticide analysis in grape juice, a fairly complex matrix due to the
      high content of sugars (~20% w/w) and pigments. A fast sample preparation method
      based on direct immersion solid-phase microextraction (SPME) was developed, and
      novel matrix compatible SPME fibers were used to reduce in-source matrix
      suppression effects. A high resolution LTQ Orbitrap mass spectrometer allowed for
      rapid quantification in full scan mode. This direct SPME-DBDI-MS approach was
      proven to be effective for the rapid and direct analysis of complex sample
      matrices, with limits of detection in the parts-per-trillion (ppt) range and
      inter- and intra-day precision below 30% relative standard deviation (RSD) for
      samples spiked at 1, 10 and 10 ng ml-1, with overall performance comparable or
      even superior to existing chromatographic approaches.

PMID- 29354814
TI  - Unravelling the mechanisms of interference between overlapping resonances.
AB  - The enhancement of the resonance lifetime that occurs upon interference of two
      overlapping resonances excited coherently by two pulses with delayed time has
      been investigated as a function of the pulse temporal width and the delay time
      between the pulses. A general law predicting quantitatively the optimal delay
      time that maximizes the lifetime enhancement of the two resonances has been
      established in terms of the pulse width and of the lifetimes of both resonances
      when they are excited isolatedly. The specific form of the law and all the
      results found can be closely related to the characteristic features of the
      mechanism of interference between the overlapping resonances, providing a
      detailed understanding on how the mechanism operates. The proposed law is
      envisioned as a useful tool to design experimental strategies to control the
      resonance lifetime.

PMID- 29354815
TI  - CoP nanoparticles anchored on N,P-dual-doped graphene-like carbon as a catalyst
      for water splitting in non-acidic media.
AB  - The design of earth-abundant, active and stable water splitting bifunctional
      catalysts that operate in the same media is crucial for large-scale water
      electrolysis. CoP nanoparticles anchored on N,P-dual-doped mesoporous graphene
      like carbon (CoP@NPMG) acts as an outstanding bifunctional electrocatalyst for
      both the hydrogen evolution reaction and the oxygen evolution reaction over a
      wide pH range. The synthesis method of CoP@NPMG is template-free and simple, and
      all the precursors are easily obtained; both these factors contribute to the
      feasibility of practical large-scale fabrication. When employed as a bifunctional
      electrode, CoP@NPMG enables high-performance water splitting with a current
      density of 10 mA cm-2 at cell voltages of only 1.58 V and 1.74 V in 1 M KOH and 1
      M PBS, respectively. In addition, CoP@NPMG displays excellent catalytic stability
      at all pH values.

PMID- 29354816
TI  - Sub-nanometer Co3O4 clusters anchored on TiO2(B) nano-sheets: Pt replaceable Co
      catalysts for H2 evolution.
AB  - Cobalt-based heterogeneous cocatalysts are important substitutions of noble metal
      cocatalysts in many important commercial chemical processes, but their efficiency
      is extremely low on a per metal atom basis, because only the atoms located at
      surface active-sites participate in the chemical reaction. Thus, cocatalysts with
      small cluster dispersions are highly desirable to maximize the amount of active
      sites and enhance the per atom efficiency. Here, we report the synthesis of sub
      nanometer Co3O4 clusters which are anchored to 2D ultrathin TiO2(B) nanosheets,
      as a cocatalyst for H2 evolution reaction (HER). It was found that the conduction
      type of Co3O4 clusters turns from P-type to N-type, and the heterojunction band
      structure between TiO2(B) and Co3O4 clusters changes from type II to type I, when
      the cluster size is reduced from nanometer scale to the sub-nanometer scale. With
      a suitable energy band matching between TiO2(B) and sub-nanometer Co3O4 clusters,
      the electrons generated in TiO2(B) during the photocatalytic process reduce the
      Co ions into metallic Co atoms, which produce excellent photocatalytic stability
      and extremely high HER efficiency comparable to that of the noble Pt cocatalyst.

PMID- 29354817
TI  - Mechanically stable ternary heterogeneous electrodes for energy storage and
      conversion.
AB  - Recently, solid asymmetric supercapacitor (ASC) has been deemed as an emerging
      portable power storage or backup device for harvesting natural resources. Here we
      rationally engineered a hierarchical, mechanically stable heterostructured
      FeCo@NiCo layered double hydroxide (LDH) with superior capacitive performance by
      a simple two-step electrodeposition route for energy storage and conversion. In
      situ scanning electron microscope (SEM) nanoindentation and electrochemical tests
      demonstrated the mechanical robustness and good conductivity of FeCo-LDH. This
      serves as a reliable backbone for supporting the NiCo-LDH nanosheets. When
      employed as the positive electrode in the solid ASC, the assembly presents high
      energy density of 36.6 W h kg-1 at a corresponding power density of 783 W kg-1
      and durable cycling stability (87.3% after 5000 cycles) as well as robust
      mechanical stability without obvious capacitance fading when subjected to bending
      deformation. To demonstrate its promising capability for practical energy storage
      applications, the ASC has been employed as a portable energy source to power a
      commercially available digital watch, mini motor car, or household lamp bulb as
      well as an energy storage reservoir, coupled with a wind energy harvester to
      power patterned light-emitting diodes (LEDs).

PMID- 29354818
TI  - Release of small bioactive molecules from physical gels.
AB  - Pharmaceutical drugs with low water solubility have always received great
      attention within the scientific community. The reduced bioavailability and the
      need of frequent administrations have motivated the investigation of new drug
      delivery systems. Within this context, drug carriers that release their payload
      in a sustained way and hence reduce the administration rate are highly demanded.
      One interesting strategy to meet these requirements is the entrapment of the
      drugs into gels. So far, the most investigated materials for such drug-loaded
      gels are derived from polymers and based on covalent linkages. However, over the
      last decade the use of physical (or supramolecular) gels derived from low
      molecular weight compounds has experienced strong growth in this field, mainly
      due to important properties such as injectability, stimuli responsiveness and
      ease of synthesis. This review summarizes the use of supramolecular gels for the
      encapsulation and controlled release of small therapeutic molecules.

PMID- 29354819
TI  - Synthesis and self-assembly behavior of polyhedral oligomeric silsesquioxane
      based triblock copolymers in selective solvents by dissipative particle dynamics
      simulation.
AB  - A polyhedral oligomeric silsesquioxane (POSS)-based hybrid triblock copolymer -
      methyl methacrylate-b-perfluoroalkylethyl methacrylate-b-methacrylisobutyl
      polyhedral oligomeric silsesquioxane (PMMA-b-PFMA-b-PMAPOSS) was synthesized via
      an atom transfer radical polymerization (ATRP) method. The self-assembly behavior
      of triblock copolymers in selective solvents of tetrahydrofuran (THF) and
      trichlorotrifluoroethane (F113) was studied using dissipative particle dynamics
      (DPD) simulation. The effects of the block sequence and volume ratio of F113/THF
      were discussed. The aggregate morphology and size were also characterized by
      transmission electron microscopy (TEM) and dynamic light scattering (DLS). The
      simulation results showed that the spherical micelle with core-shell-corona or
      core-mixed shell structure could be formed and the micelle size increased with
      the F113 content, which was in qualitative agreement with the experimental
      results. The DPD simulation revealed the dynamic process of the formation of
      aggregates at the mesoscopic scale, which can be considered as an adjunct to
      experiments and provides other valuable information for the experiments.

PMID- 29354820
TI  - Asiatic acid suppresses neuroinflammation in BV2 microglia via modulation of the
      Sirt1/NF-kappaB signaling pathway.
AB  - Asiatic acid, a triterpenoid derived from Centella asiatica, has been found to
      exhibit multiple bioactivities. In this study, we investigated the effects of
      asiatic acid on lipopolysaccharide (LPS)-induced neuroinflammation and explored
      the mechanism of its action in BV2 microglia. We found that asiatic acid (0.1 to
      100 MUM) treatment significantly attenuated nitric oxide (NO) production and
      inhibited inducible nitric oxide synthase (iNOS) expression in a concentration
      dependent manner following LPS exposure. Asiatic acid reduced LPS-induced
      expression and secretion of inflammatory cytokines, including tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)
      in BV2 cells. In addition, asiatic acid enhanced Sirt1 expression, reduced NF
      kappaB p65 acetylation, and suppressed NF-kappaB activation after LPS
      stimulation. However, EX-527, an inhibitor of Sirt1, abolished the inhibitory
      effects of asiatic acid on LPS-stimulated microglia activation. These findings
      suggest that asiatic acid prevents LPS-induced neuroinflammation via regulating
      the Sirt1/NF-kappaB signaling pathway.

PMID- 29354821
TI  - Pressure-induced chemical reactions in the N2(H2)2 compound: from the N2 and H2
      species to ammonia and back down into hydrazine.
AB  - Theory predicts a very rich high pressure chemistry of hydronitrogens with the
      existence of many NxHy compounds. The stability of these phases under pressure is
      being investigated by the compression of N2-H2 mixtures of various compositions.
      A previous study had disclosed a eutectic-type N2-H2 phase diagram with two
      stoichiometric van der Waals compounds: (N2)6(H2)7 and N2(H2)2. The structure and
      pressure induced chemistry of the (N2)6(H2)7 compound have already been
      investigated. Here, we determine the structure of the N2(H2)2 compound and
      characterize using Raman spectroscopy measurements the chemical changes under a
      pressure cycle up to 60 GPa and back to ambient conditions. A N2(H2)2 single
      crystal was grown from a 1 : 2 N2-H2 mixture and its crystalline structure was
      solved using synchrotron X-ray diffraction. Similar to the (N2)6(H2)7 solid,
      N2(H2)2 has a remarkable host-guest structure containing N2 molecules
      orientationally disordered with spherical, ellipsoidal and planar shapes. Above
      50 GPa, N2(H2)2 was found to undergo a chemical reaction. The reaction products
      were determined to be of the azane family, with NH3 as the main constituent,
      along with molecular nitrogen. Upon pressure decrease, the reaction products are
      found to react in such a way that below 10 GPa, hydrazine is the sole azane
      detected. Observed down to the opening of the diamond anvil cell, the formation
      of metastable hydrazine instead of the energetically favorable ammonia is
      puzzling and remains to be elucidated. That could change the current view of
      Jovian planets' atmospheres in which ammonia is assumed the only stable
      hydronitrogen molecule.

PMID- 29354822
TI  - Ab initio calculations of heavy-actinide hexahalide compounds: do these heavy
      actinides behave like their isoelectronic lanthanide analogues?
AB  - Research on heavy actinides has experienced an increased interest in the last few
      years due to new synthetic techniques and recent technological advances that have
      allowed for obtaining important information even from very small samples. This
      area presents challenges not only from the experimental point of view but also
      from the theoretical perspective. This work deals with a multiconfigurational
      CASSCF and NEVPT2 benchmark study based on a two-step methodology that considers
      first correlation effects and then the spin-orbit coupling applied to berkelium
      (Bk), californium (Cf), einsteinium (Es) and fermium (Fm) hexahalides. Optical
      properties, such as f -> d transitions and crystal-field parameters, have been
      calculated and rationalized. The results for these trivalent actinides indicate
      that the electronic structure of the low-lying states is reproduced accurately
      with small basis sets. The ground-state multiplets are isolated, in the same
      manner as their isoelectronic lanthanide counterparts. In the case of tetravalent
      berkelium, the picture is different regarding the electronic structure where
      crystal-field theory fails due to considerable ligand-to-metal charge transfer
      contributions to the ground state.

PMID- 29354823
TI  - A metal-calixarene coordination nanotube with 5-(pyrimidin-5-yl)isophthalic acid.
AB  - A metal-organic nanotube (MONT) was assembled by bridging the truncated metal
      calixarene octahedra with coordinating water molecules. Remarkably, the tubular
      compound exhibited a much higher sorption capacity for C2H6 and C3H8 than for
      CH4, and hence represents a promising material for separating these gases. The
      addition of a little NiSO4 into the reaction system led to the formation of a 2D
      metal-calixarene network.

PMID- 29354824
TI  - A high-speed network of nanoswitches for on/off control of catalysis.
AB  - NetState I of the communication-catalysis protocol is defined by a 1 : 1 mixture
      of the nanoswitches [Cu(1)]+ and 2. Upon one-electron oxidation at the ferrocenyl
      unit of the switch [Cu(1)]+, copper(i) ions are released that after translocation
      toggle nanoswitch 2 -> [Cu(2)]+ (NetState II) within 4 min. NetState I was fully
      reset within 1 min by reduction of 1+ -> 1. Running this redox-triggered
      switching protocol in the presence of 4-nitrobenzaldehyde, diethyl malonate and
      piperidine (catalyst) allows toggling of a catalyzed Knoevenagel addition from ON
      to OFF and back to ON.

PMID- 29354825
TI  - Linear humidity response of carbon dot-modified molybdenum disulfide.
AB  - Molybdenum disulfide (MoS2)-based humidity sensors suffer from low sensitivity
      and long response time. Herein, this problem has been effectively solved by
      modifying MoS2 nanosheets using carbon dots (CDs) with abundant functional groups
      via a convenient and facile hydrothermal method. The mechanism for the enhanced
      humidity response of CD-modified MoS2 has been proposed through the
      characterization of physical and chemical properties of the as-prepared
      composites. The introduction of CDs is expected to enhance the adsorption of
      water molecules by increasing the specific surface area and surface active sites
      of the MoS2 nanosheets. Moreover, a three-dimensional conductive network is
      jointly established by the chemisorbed water molecules, CDs, and MoS2 nanosheets,
      which ensures continuous transmission of charges in a low humidity environment.
      As a result, the response performance and the repeatability have been
      significantly improved in CD-MoS2-based humidity sensors. The response curve
      shows an excellent linear property in the range of 15-80% RH. This study
      demonstrates the potential applications of CD-modified two-dimensional
      nanomaterials with their improved performance towards humidity sensing.

PMID- 29354826
TI  - An access to 1,3-azasiline-fused quinolinones via oxidative heteroannulation
      involving silyl C(sp3)-H functionalization.
AB  - A Mn-promoted intermolecular oxidative radical heteroannulation of N-(2
      cyanoaryl)-acrylamides and tertiary silanes has been described, which provides an
      efficient route to produce silicon/nitrogen heterocycles, sila-analogues of the
      known carbon-based structural motifs prevalent in bioactive natural products,
      pharmaceuticals and materials. The reaction enables Si-incorporation by
      controlling accurately several chemical bond cleavage and formation processes.
      Moreover, this reaction represents a new one-step construction of 1,3-azasiline
      fused quinolinones that was achieved via silyl C(sp3)-H functionalization using
      an oxidative radical strategy.

PMID- 29354827
TI  - Intense excimer CPL of pyrenes linked to a quaternaphthyl.
AB  - (R,R,R)-Quaternaphthyls possessing eight and six pyrenes (compounds 4 and 3)
      displayed intense excimer-CPL. The glum values in solution and in the solid state
      were +0.034-0.037 and +0.0053-0.0056, respectively. The glum values of 3 and 4
      were indistinguishable, indicating that the pyrenes of 3 and 4 assumed the same
      conformation, even in excited states. The intense CPL was caused by
      conformationally rigid pyrenes arranged via the cumulative steric effects along
      the quaternaphthyl axis.

PMID- 29354828
TI  - Azaborines: synthesis and use in the generation of stabilized boron-substituted
      carbocations.
AB  - A formal N-heterocyclic carbene insertion into the B-H bond of 9-BBN followed by
      a ring expansion reaction is reported. NHC-9-BBN adducts were reacted in one or
      two steps to give the corresponding di- or triazaborines. Hydride abstraction of
      selected species with [Ph3C]+ is facile, giving rise to 6pi-aromatic cations with
      Lewis acidity comparable to Lewis acids commonly employed in frustrated Lewis
      pairs.

PMID- 29354829
TI  - A luminescent bimetallic iridium(iii) complex for ratiometric tracking
      intracellular viscosity.
AB  - A luminescent bimetallic iridium probe C10 was developed through a long soft
      carbon chain linkage to achieve ratiometric detection of viscosity. C10 features
      high sensitivity and selectivity for viscosity. More importantly, C10 is living
      cell permeable and can be employed to distinguish cancer cells from normal cells
      and track viscosity changes during MCF-7 cell apoptosis.

PMID- 29354830
TI  - Dehydrohalogenation of proton responsive complexes: versatile aggregation via
      pyrazolate pincer ligand arms.
AB  - The behavior of the complex (H2L)CoCl2, where H2L is a bis-(pyrazol-3
      yl)pyridine, towards Bronsted bases is studied, to evaluate peripheral NH
      deprotonation as a route to a dianionic pincer ligand on a d7 center.
      Deprotonation is found to also remove chloride from cobalt, and the decreased
      metal coordination number is then satisfied by bimolecular reaction of the newly
      formed peripheral deprotonated pyrazolate nitrogen, leading to Co2 units bridged
      by some of the pyrazolates, in the analogous species [Co2(L)(LH)]2(L) and
      [Co2(L)(HL)]2[Co(L)2], but also occasionally by chloride retention, in LiCo2L2Cl.
      Reacting LiCo2L2Cl with tBuNC, yields monomeric LCo(tBuNC)2, shown to be a 17
      valence electron species. Use of excess LiN(SiMe3)2 in deprotonation of
      (H2L)CoCl2 leads to a product containing a Co[N(SiMe3)2]2 substructure, which
      illustrates opening of the Co2L2 dimer in response to an attacking nucleophile.

PMID- 29354831
TI  - Thermoelectric Bi2Te3-xSex alloys for efficient thermal to electrical energy
      conversion.
AB  - Eco-friendly renewable energy conversion methods are constantly investigated.
      Thermoelectric devices, directly converting thermal into electrical energy, show
      high potential for utilizing waste heat into useful electricity. Yet enhancing
      their efficiency is a challenging task. Below 300  degrees C, Bi2TexSe3-x
      thermoelectric alloys are considered to be the most efficient for such
      applications. In the current research, by controlling the specific compositions
      and the synthesis route, optimizing the electron doping level and minimizing the
      lattice thermal conductivity values, very high thermoelectric figure of merit
      values were obtained beyond ~170  degrees C. It is shown that upon combining the
      currently reported Bi2Te2.4Se0.6 and Bi2Te1.5Se1.5 alloys with previously
      reported highly efficient p- and n-type Bi2Te3 based compositions, a remarkable
      thermoelectric efficiency of ~9.6% can be achieved for a relatively low
      temperature difference of 250  degrees C.

PMID- 29354832
TI  - Fluorescent squaramides as anion receptors and transmembrane anion transporters.
AB  - A series of squaramide-based anion transporters functionalised with the 1,8
      naphthalimide fluorophore has been developed for improved ionophoric activity and
      fluorescent imaging in cells.

PMID- 29354833
TI  - Empirical study of physicochemical and spectral properties of CuII-containing
      chelate-based ionic liquids.
AB  - The physicochemical properties including melting point, density, viscosity,
      conductivity, and surface tension as well as spectral properties such as infrared
      and EPR spectra of the chelate-based ILs [Cnmim][Cu(F6-acac)3] (n = 6, 8, 10, 12,
      14) were studied as functions of temperature and chain length. The thermodynamic
      properties such as the standard molar entropy and crystal energy were estimated
      by Glasser's theory, the molar enthalpy of vaporization was calculated by Kabo's
      method, and the ionicity was estimated by the Walden rule. Compared with the
      common ILs, the chelate-based ILs have larger molecular volume, larger density,
      smaller crystal energy, poorer ionicity and larger enthalpy of vaporization. The
      infrared spectra data of the ILs showed a red shift of the C-H bond stretching
      vibration of the alkyl chain in the cation and the EPR spectra showed that the
      crystal field of Cu2+ was kept when the chain length was elongated, which
      indicated the existence of microphase separation in the ILs. This work is helpful
      in understanding the structure-property relations of chelate-based ILs for
      further application.

PMID- 29354834
TI  - Buckling vs. particle desorption in a particle-covered drop subject to
      compressive surface stresses: a simulation study.
AB  - Predicting the behaviour of particle-covered fluid interfaces under compression
      has implications in several fields. The surface-tension driven adhesion of
      particles to drops and bubbles is exploited for example to enhance the stability
      of foams and emulsion and develop new generation materials. When a particle
      covered fluid interface is compressed, one can observe either smooth buckling or
      particle desorption from the interface. The microscopic mechanisms leading to the
      buckling-to-desorption transition are not fully understood. In this paper we
      simulate a spherical drop covered by a monolayer of spherical particles. The
      particle-covered interface is subject to time-dependent compressive surface
      stresses that mimic the slow deflation of the drop. The buckling-to-desorption
      transition depends in a non-trivial way on three non-dimensional parameters: the
      ratio Pis/gamma of particle-induced surface pressure and bare surface tension,
      the ratio a/R of particle and drop radii, and the parameter f characterising the
      strength of adhesion of each particle to the interface. Based on the insights
      from the simulations, we propose a configuration diagram describing the effect of
      these controlling parameters. We find that particle desorption is highly
      correlated with a mechanical instability that produces small-scale undulations of
      the monolayer of the order of the particle size that grow when the surface
      pressure is sufficiently large. We argue that the large local curvature
      associated with these small undulations can produce large normal forces,
      enhancing the probability of desorption.

PMID- 29354835
TI  - Guanidinium/ammonium competition and proton transfer in the interaction of the
      amino acid arginine with the tetracarboxylic 18-crown-6 ionophore.
AB  - The recognition of arginine plays a central role in modern proteomics and
      genomics. Arginine is unique among natural amino acids due to the high basicity
      of its guanidinium side chain, which sustains specific interactions and proton
      exchange biochemical processes. The search for suitable macrocyclic ionophores
      constitutes a promising route towards the development of arginine receptors. This
      study evaluates the conformational features involved in the binding of free
      arginine by the polyether macrocycle (18-crown-6)-tetracarboxylic acid. Infrared
      action vibrational spectroscopy and quantum-chemical computations are combined to
      characterize the complexes with net charges +1 and +2. The spectrum of the +1
      complex can be explained in terms of a configuration predominantly stabilized by
      a robust bidentate coordination of guanidinium with a carboxylate group formed
      from the deprotonation of one side group of the crown ether. The released proton
      is transferred to the amino terminus of arginine, which then coordinates with the
      crown ether ring. In an alternative type of conformation, partly consistent with
      experiment, the amino terminus is neutral and the guanidinium group inserts into
      the crown ether cavity. In the +2 complexes, arginine is always doubly protonated
      and the most stable conformations are characterized by a tripodal coordination of
      the ammonium -NH3+ group of arginine with the oxygen atoms of the macrocycle
      ring, while the interactions of the amino acid with the side carboxylic acid
      groups of the crown ether acquire a remarkable lesser role.

PMID- 29354836
TI  - An efficient exciton harvest route for high-performance OLEDs based on
      aggregation-induced delayed fluorescence.
AB  - We managed to integrate the features of aggregation-induced emission (AIE) and
      thermally activated delayed fluorescence (TADF), by introducing a fluorine atom
      into the quinoxaline system for highly efficient fluorescent OLEDs. With a
      purposive design and well-controlled synthesis, two novel AIE-TADF compounds were
      demonstrated and characterized. Monofluoro-substituted SFDBQPXZ exhibited high
      efficiencies in a doped OLED with a maximum EQE of 23.5%, a maximum current
      efficiency (CE) of 78.3 cd A-1 and a maximum power efficiency (PE) of 91.1 lm W
      1. Noteworthily, by employing SFDBQPXZ as an orange emitter in a non-doped
      device, we have realized a considerably high EQE over 10%. The high efficiency
      and low roll-off in the doped or non-doped devices make our strategy promising
      and meaningful for OLED applications.

PMID- 29354837
TI  - A stable free tetragermacyclobutadiene incorporating fused-ring bulky EMind
      groups.
AB  - The first free cyclobutadiene (CBD) germanium analogue was obtained as room
      temperature stable dark red crystals via the reaction of the bulky EMind
      substituted 1,2-dichlorodigermene with lithium naphthalenide. The cyclic 4pi
      electron antiaromaticity is essentially stabilized by the polar Jahn-Teller
      distortion in the germanium CBD producing a planar rhombic-shaped charge
      separated structure.

PMID- 29354838
TI  - Remarkable hydrogen storage properties of MgH2 doped with VNbO5.
AB  - The present work concerns the catalytic effect of VNbO5, a ternary oxide prepared
      via a solid-state route, on the sorption performance of MgH2. Three doped
      systems, namely 5, 10 and 15 wt% VNbO5-MgH2 have been prepared by ball milling
      and thoroughly characterized. Hydrogen sorption, evaluated by temperature
      programmed desorption experiments, revealed a significant reduction of the
      desorption temperature from 330  degrees C for the un-doped sample (prepared and
      tested for comparison) to 235  degrees C for the VNbO5-doped sample. Furthermore,
      more than 5 wt% of hydrogen can be absorbed in 5 minutes at 160  degrees C under
      20 bar of hydrogen, which is remarkable compared to the 0.7 wt% achieved for the
      un-doped system. The sample doped with 15 wt% of additive, showed good
      reversibility: over 5 wt% of hydrogen with negligible degradation even after 70
      consecutive cycles at 275  degrees C and 50 cycles at 300  degrees C. The
      kinetics analysis carried out by Kissinger's method exhibited a considerable
      reduction of the activation energy for the desorption process. Finally, pressure
      composition-isotherm experiments conducted at three different temperatures
      allowed estimating the thermodynamic stability of the system and shed light on
      the additive role of VNbO5.

PMID- 29354839
TI  - Effects of adatom and gas molecule adsorption on the physical properties of
      tellurene: a first principles investigation.
AB  - Tellurene is a new member of the two-dimensional (2D) materials' family, whose
      existence has been recently confirmed by first principles calculation and
      experimental work. Tellurene is also the first 2D mono-elemental material of
      group-VI predicted by scientists, and investigations of its basic properties are
      still in their infancy. In this study, we use first principles calculation based
      on density functional theory to investigate the adsorption of nineteen typical
      adatoms (Li, Na, K, Ca, Fe, Co, Ni, Cu, Zn, Ag, Au, Pd, Pt, B, N, O, Si, Cl, and
      Al), and five typical gas molecules (H2, O2, H2O, NO2, and NH3) on alpha-phase as
      well as beta-phase tellurene sheets. Our calculations shows that most adatoms are
      chemisorbed on tellurene sheets with large adsorption energies. Moreover, some of
      the adatoms are observed to give rise to distinct structural deformations and
      even local reconstructions. We report that a variety of electronic states are
      induced by the adatoms, which implies that different electronic structures can be
      engineered by the adsorption of adatoms. In fact, n-type doping, p-type doping,
      half-metal, and spin-gapless semiconductor features can be acquired by doping
      adatoms on tellurene sheets. Our calculations also show that the five gas
      molecules are all physisorbed on tellurene sheets, and no splitting behaviors are
      observed. Therefore, the adsorption of the five gas molecules has a weak effect
      on the electronic properties of tellurene. To conclude, our results indicate that
      adatom engineering may be used to greatly expand the potential applications of 2D
      tellurene.

PMID- 29354840
TI  - Electrochemical processes on solid shaped nanoparticles with defined facets.
AB  - This 2007 Chemistry Nobel prize update covers scientific advances of the past
      decade in our understanding of electrocatalytic processes on surfaces of
      nanoscale shape-controlled polyhedral solids. It is argued that the field of
      chemical reaction processes on solid surfaces has recently been paying increasing
      attention to the fundamental understanding of electrified solid-liquid interfaces
      and toward the operando study of the minute fraction of catalytically active,
      structurally dynamic non-equilibrium Taylor-type surface sites. Meanwhile,
      despite mounting evidence of acting as structural proxies in some cases, the
      concept of catalytic structure sensitivity of well-defined nanoscale solid
      surfaces continues to be a key organizing principle for the science of shape
      controlled nanocrystals and, hence, constitutes a central recurring theme in this
      review. After addressing key aspects and recent progress in the wet-chemical
      synthesis of shaped nanocatalysts, three areas of electrocatalytic processes on
      solid shape-controlled nanocrystals of current scientific priority are discussed
      in more detail: the oxygen electroreduction on shape-controlled Pt-Ni polyhedra
      with its technological relevance for low temperature fuel cells, the CO2
      electroreduction to hydrocarbons on Cu polyhedra and the puzzling interplay
      between chemical and structural effects, and the electrocatalytic oxygen
      evolution reaction from water on shaped transition metal oxides. The review
      closes with the conclusion that Surface Science and thermal catalysis, honored by
      Ertl's Nobel prize a decade ago, continue to show major repercussions on the
      emerging field of Interface Science.

PMID- 29354841
TI  - Recent progress in the isolation, bioactivity, biosynthesis, and total synthesis
      of natural spiroketals.
AB  - Covering: 2011 to July 2017.Spiroketal (spiroacetal), a common moiety in numerous
      natural products, drugs and functional molecules, has been a central topic in
      organic chemistry for a long time. Owing to their structural diversity, important
      bioactivity and functional irreplaceability, natural spiroketals have attracted
      the interest of natural product chemists, medical chemists, biological chemists,
      agricultural chemists, synthetic chemists, and chemical biologists. In this
      review, we focus on the overview of the isolation, bioactivity, biosynthesis and
      total synthesis of spiroketals from 2011 to July 2017.

PMID- 29354842
TI  - A novel trigonal propeller-shaped hybrid tri-neodymium-polyoxometalate exhibiting
      single-molecule magnet behavior.
AB  - A trigonal propeller-shaped hybrid polyoxometalate (POM)
      (NH2Me2)3{[Nd(Mo4O13)(DMF)4]3(BTC)2}.8DMF (1; BTC = 1,3,5-benzenetricarboxylate)
      has been synthesized and structurally characterized. The planar {Mo4} segment is
      tailored from the precursor Lindqvist polyoxoanion [Mo6O19]2- firstly, and plays
      a key role in the reassembly of 1. Furthermore, the magnetic studies reveal that
      1 shows single-molecule magnet (SMM) behavior.

PMID- 29354843
TI  - A series of unprecedented triol-stabilized [H3MW6O24]n-: the missing piece
      between A- and B-type Anderson-Evans polyoxometalates.
AB  - Several novel triol-ligands functionalized Anderson-Evans type polyoxotungstates,
      K3Na3[{HOCH2C(CH2O)3}AlO3W6O18], K3Na3[{HOCH2C(CH2O)3}CrO3W6O18],
      K3Na3[{HOCH2C(CH2O)3}CoO3W6O18], and K3Na3[{H3CC(CH2O)3}CoO3W6O18], were
      successfully synthesized and characterized, in which some of the central metal
      ions have never been found in the Anderson-type polyoxotungstates. The single
      crystal X-ray diffraction analysis indicated that the clusters were on a status,
      in which only one-side MU3-O was protonated. This indicates that the three
      protonated cluster is a common type of Anderson cluster aside zero-protonated (A
      type) and six-protonated (B-type), which could be named as the T-type.

PMID- 29354844
TI  - Cobalt(ii)-catalyzed chelation-assisted C-H iodination of aromatic amides with
      I2.
AB  - The cobalt-catalyzed chelation-assisted iodination of aromatic amides using
      molecular I2 as an iodinating reagent is reported. 8-Amino-5-chloroquinoline
      functions as an efficient directing group. This mild and air stable catalytic
      system shows a wide functional group tolerance and improved synthetic
      accessibility.

PMID- 29354845
TI  - An injectable supramolecular hydrogel hybridized with silver nanoparticles for
      antibacterial application.
AB  - Silver nanoparticles (AgNPs) show long-lasting and broad-spectrum antibacterial
      activity. Herein, PEGylated AgNPs were prepared in situ by complexing AgNO3 with
      the random copolymer of poly(ethylene glycol) methyl ether methacrylate (PEGMA)
      and polyacrylic acid via electrostatic interaction followed by in situ reduction.
      AgNP hybrid supramolecular hydrogels were thus prepared through host-guest
      inclusion between PEGMA side chains and alpha-cyclodextrins in aqueous solution.
      The hydrogels were physically cross-linked by both pseudopolyrotaxane
      crystallization and AgNPs, which showed temperature responsiveness and self
      healing properties. By hybridizing AgNPs, the hydrogels showed excellent
      antibacterial properties against S. aureus and E. coli bacteria as well as low
      cytotoxicity and have potential applications as injectable antibacterial
      materials.

PMID- 29354846
TI  - Nickel-catalyzed cross-coupling of beta-carbonyl alkenyl pivalates with arylzinc
      chlorides.
AB  - The nickel-catalyzed cross-coupling reaction of beta-carbonyl alkenyl pivalates
      with arylzinc reagents generates 3-aryl-substituted alpha,beta-unsaturated
      carbonyl compounds via C-O bond cleavage. The reaction features mild reaction
      conditions, a wide scope of substrates, and good functional group tolerance.

PMID- 29354847
TI  - Dopamine functionalization of BaTiO3: an effective strategy for the enhancement
      of electrical, magnetoelectric and thermal properties of BaTiO3-PVDF-TrFE
      nanocomposites.
AB  - Electro-active polymer-ceramic composite systems are emerging materials in the
      fields of nanoelectronic, microelectromechanical and macroelectronic device
      applications. Still more precise and concise research studies have yet to come in
      the areas of energy storage, harvesting, energy conversion, etc. In line with
      this, we have synthesized and analyzed PVDF-TrFE based nanocomposites of both
      functionalized and non-functionalized BaTiO3 (BTO). All the samples were prepared
      as free standing films by employing a solvent cast method. A systematic study of
      structural, morphological, thermal, dielectric, ferroelectric, piezoelectric and
      magnetoelectric (ME) properties has been carried out. It has been reported that
      the addition of BTO nanoparticles (with and without functionalization) into a
      polymer matrix substantially improved the properties of the nanocomposite. By
      performing the above mentioned characterization, it could be proved that dopamine
      functionalized BTO (DBTO) samples are better choices for the above mentioned
      applications including magnetoelectric applications, than the non-functionalized
      ones.

PMID- 29354848
TI  - The role of polyethylenimine in enhancing the efficiency of quantum dot light
      emitting devices.
AB  - Although the use of polyethylenimine (PEI) in quantum dot light-emitting devices
      (QDLEDs) has recently been found to improve efficiency, the mechanism behind this
      increase has been disputed in the literature. In this work, we conduct
      investigations to elucidate the role of PEI in enhancing QDLED efficiency.
      Spectroscopic studies of devices with a phosphorescent marking layer reveal that
      the PEI layer increases, rather than decreases, the generation of excitons within
      the hole transporting layer indicative of increased electron injection. Delayed
      electroluminescence measurements corroborate these findings as devices with a PEI
      interlayer exhibit a greater concentration of excess mobile and trapped
      electrons. We attribute the improvement in efficiency despite the ensuing
      increased charge imbalance within the devices to the passivation of exciton
      quenching at the ZnO/QD interface. The increase in efficiency predominantly
      occurs over low driving currents which is particularly attractive for the
      brightness targets of display applications. Furthermore, despite the increased
      charge imbalance, the PEI passivation layer appears to have little effect on
      QDLED stability. This shows that excess electrons and Auger quenching by
      unneutralized electrons are not detrimental to QDLED stability.

PMID- 29354849
TI  - Low risk of intra-abdominal infections in rectal cancer patients treated with
      Hartmann's procedure: a report from a national registry.
AB  - PURPOSE: To describe the postoperative surgical complications in patients with
      rectal cancer undergoing Hartmann's procedure (HP). METHODS: Data were retrieved
      from the Swedish Colorectal Cancer Registry for all patients with rectal cancer
      undergoing HP in 2007-2014. A retrospective analysis was performed using
      prospectively recorded data. Characteristics of patients and risk factors for
      intra-abdominal infection and re-laparotomy were analysed. RESULTS: Of 10,940
      patients resected for rectal cancer, 1452 (13%) underwent HP (median age, 77
      years). The American Society of Anesthesiologists (ASA) score was 3-4 in 43% of
      patients; 15% had distant metastases and 62% underwent a low HP. The intra
      abdominal infection rate was 8% and re-laparotomy rate was 10%. Multivariable
      logistic regression analysis identified preoperative radiotherapy (OR, 1.78; 95%
      CI, 1.14-2.77), intra-operative bowel perforation (OR, 1.99; 95% CI, 1.08-3.67),
      T4 tumours (OR, 1.68; 95% CI 1.04-2.69) and female gender (OR, 1.73; 95% CI, 1.15
      2.61) as risk factors for intra-abdominal infection. ASA score 3-4 (OR, 1.62; 95%
      CI, 1.12-2.34), elevated BMI (OR, 1.05; 95% CI, 1.02-1.09) and female gender (OR,
      2.06; CI, 1.41-3.00) were risk factors for re-laparotomy after HP. The rate of
      intra-abdominal infection was not increased after a low HP. CONCLUSIONS: Despite
      older age and co-morbidities including more advanced cancer, patients undergoing
      Hartmann's procedure had low rates of serious postoperative complications and re
      laparotomy. A low HP was not associated with a higher rate of intra-abdominal
      infection. HP seems to be appropriate for old and frail patients with rectal
      cancer.

PMID- 29354850
TI  - C11orf95-RELA fusions and upregulated NF-KB signalling characterise a subset of
      aggressive supratentorial ependymomas that express L1CAM and nestin.
AB  - Ependymomas (EPN) show site specific genetic alterations and a recent DNA
      methylation profiling study identified nine molecular subgroups. C11orf95-RELA
      and YAP1 fusions characterise the RELA and YAP1 molecular subgroups,
      respectively, of supratentorial (ST)-EPNs. Current guidelines recommend molecular
      subgrouping over histological grade for accurate prognostication.
      Clinicopathological features of ST-EPNs in correlation with C11orf95-RELA and
      YAP1 fusions have been assessed in only few studies. We aimed to study these
      fusions in EPNs, and identify diagnostic and prognostic markers. qRT-PCR and
      Sanger Sequencing for the detection of C11orf95-RELA, YAP1-MAMLD1 and YAP1
      FAM118B fusion transcripts, gene expression analysis for NFKB1, and
      immunohistochemistry for p53, MIB-1, nestin, VEGF, and L1CAM were performed. 88
      EPNs (10-Grade I and 78-Grade II/III) from all sites were included. RELA fusions
      were unique to Grade II/III ST-EPNs, detected in 81.4% (22/27) and 18.5% (5/27)
      of pediatric and adult ST-EPNs respectively. ST-EPNs harbouring RELA fusions
      showed frequent grade III histology (81.5%), clear cell morphology (70.3%),
      upregulated NFKB1 expression, MIB-1 labelling indices (LI) >= 10% (77.8%), and
      immunopositivity for nestin (95.7%), VEGF (72%), L1CAM (79%), and p53 (64%).
      Presence of RELA fusions, L1CAM immunopositivity and MIB-1 LI >= 10% associated
      with poor outcome. L1CAM showed 81% concordance with RELA fusions. YAP1-MAMLD1
      fusion was identified in a single RELA fusion negative adult anaplastic ST-EPN.
      RELA fusions are frequent in ST-EPNs and associate with poor outcome. L1CAM is a
      surrogate immunohistochemical marker. RELA fusion positive ST-EPNs strongly
      express nestin indicating increased stemness. Further evaluation of the
      interactions between NFKB and stem cell pathways is warranted.

PMID- 29354851
TI  - Correction to: Biomonitoring of Trace Metals in the Keban Dam Reservoir (Turkey)
      Using Mussels (Unio elongatulus eucirrus) and Crayfish (Astacus leptodactylus).
AB  - The original version of this article contained mistakes: the units mg/kg-1 and
      MUg/kg-1 found on tables 1, 2, 4, 5 and 6 should be mg kg-1 and MUg kg-1,
      respectively.

PMID- 29354852
TI  - Cadmium exposure triggers genotype-dependent changes in seed vigor and
      germination of tomato offspring.
AB  - Although negative effects on the offspring fitness can be triggered by the mother
      plant exposure to environmental stresses, some plants are able to "remember" past
      incidents and enhance the progeny tolerance. Here, the mineral profile,
      cytogenetic modifications, and physiological potential of seeds from two tomato
      cultivars, with contrasting tolerance degrees to cadmium (Cd) toxicity, were
      evaluated after plant exposure to this metal. Both cultivars exhibited high Cd
      translocation to the seeds; however, the tolerant tomato accumulated more Cd than
      did the sensitive one. As a consequence of the Cd accumulation, reductions in the
      Mn concentration in Cd-challenged plants were detected. Surprisingly, seed
      germination and vigor were increased in the tolerant tomato cultivar after Cd
      exposure, despite increases in the chromosomal abnormalities. By contrast, seeds
      from the sensitive cultivar exhibited no changes in their physiological potential
      after Cd exposure, despite Cd-induced reductions in the mitotic index. Moreover,
      bunch position exerted effects on the vigor and type of chromosomal abnormality.
      The results show that maternal plant exposure to Cd can affect tomato offspring
      by changing the seed physiological potential, and such effect can be partially
      explained by alterations in the seed-derived elements (essential and non
      essential) and genotype-dependent tolerance mechanisms.

PMID- 29354853
TI  - Lead-resistant bacteria from Saint Clair River sediments and Pb removal in
      aqueous solutions.
AB  - Lead is an extensive contaminant. Pb-resistant bacterial strains were isolated
      from Saint Clair River sediments on two enrichment media with increasing
      concentrations of Pb (NO3)2. Bacterial strains that grew at 1.25 or 1.5 g L-1 of
      Pb (NO3)2 L-1) were purified and selected for further study. Ninety-seven Pb
      resistant strains were screened for the ability to produce bioflocculants. The
      majority of the Pb-resistant strains demonstrated moderate to high flocculation
      activity. Metal removal assays demonstrated that the higher is the flocculation
      activity, the higher is the efficiency of metal removal. In the multi-metal
      solutions, the bacterial strain with the highest flocculation activity (R19) had
      the highest metal removing capability (six out of eight metals) and the highest
      metal removal efficiency. The highly selective affinity towards Pb2+ observed for
      strain R19 suggests its use for the recovery of Pb2+ from multiple metal
      solutions. Because they are well adapted to unfavorable conditions due to their
      resistance to metals (e.g., Pb) and antibiotics, these characteristics may help
      in developing an effective process for wastewater treatment using these strains.

PMID- 29354854
TI  - Immunological features and efficacy of the recombinant subunit vaccine LTB-EMY162
      against Echinococcus multilocularis metacestode.
AB  - Alveolar echinococcosis is a zoonotic disease caused by the infection of the
      larval stage Echinococcus multilocularis with worldwide distribution especially
      in the northwest China. It is important to develop a well-tolerated
      immunoprophylaxis against E. multilocularis for alveolar echinococcosis control.
      In this study, a prokaryotic expression system for recombinant immunogen LTB
      EMY162 was established, and the immunological features, sensitized lymphocyte, IL
      4/IFN-gamma secreted, prophylactic effect, and therapeutic effect were also
      evaluated. Arctic Express (DE3) system, Ni2+-charged and molecular sieve
      chromatography were used to obtain a high-purity 29 kDa protein. The ELISA and
      lymphocyte proliferation assay showed that LTB-EMY162 induced high-titer specific
      IgG against EMY162 and E. multilocularis protoscoleces protein in BALB/c mice and
      promoted sensitized T lymphocyte cell proliferation, and LTB-EMY162 stimulated Th
      cell to secrete IL-4 and IFN-gamma and induced a Th1/Th2 mixed type immunological
      response. We also found that LTB-EMY162 significantly inhibited the cysts
      formation by challenging with 1000 E. multilocularis protoscoleces. The growth of
      protoscoleces and cysts were also significantly decreased by treating with LTB
      EMY162 in 1000 protoscoleces intraperitoneal injection therapeutic mice model. In
      conclusion, we have constructed a subunit vaccine LTB-EMY162 which has prevention
      and therapeutic effect against E. multilocularis infection.

PMID- 29354856
TI  - Is trade openness good for environment in South Korea? The role of non-fossil
      electricity consumption.
AB  - The paper investigates the linkage of carbon dioxide (CO2) emissions, per capita
      real output, share of non-fossil electricity consumption, and trade openness in
      South Korea from 1971 to 2013. The empirical results indicate that the
      environmental Kuznets curve (EKC) is supported by autoregressive distributed lag
      (ARDL) test. Both short- and long-run estimates indicate that increasing non
      fossil electricity consumption can mitigate environmental degradation, and
      increasing trade aggravates carbon dioxide emissions. By Granger causality, long
      run causalities are found in both equations of CO2 emissions and trade openness,
      as well as exports and imports. In the short-run, evidence indicates feedback
      linkage between output and trade, unidirectional linkages from trade to
      emissions, from emissions to output, and from output to non-fossil electricity
      use. Therefore, South Korea should strengthen the sustainable economy, consume
      clean energy, and develop green trade.

PMID- 29354855
TI  - Combined treatment of contaminated soil with a bacterial Stenotrophomonas strain
      DXZ9 and ryegrass (Lolium perenne) enhances DDT and DDE remediation.
AB  - Bioremediation of contaminated soils by a combinational approach using specific
      bacterial species together with ryegrass is a promising strategy, resulting in
      potentially highly efficient degradation of organic contaminants. The present
      study tested the combination of strain DXZ9 of Stenotrophomonas sp. with ryegrass
      to remove DDT and DDE contaminants from soil under natural conditions in a pot
      experiment. The strain DXZ9 was successfully colonized in the natural soil,
      resulting in removal rates of approximately 77% for DDT, 52% for DDE, and 65% for
      the two pollutants combined after 210 days. Treatment with ryegrass alone
      resulted in slightly lower removal rates (72 and 48%, respectively, 61% for both
      combined), while the combination of strain DXZ9 and ryegrass significantly (p <
      0.05) improved the removal rates to 81% for DDT and 55% for DDE (69% for both).
      The half-life of the contaminants was significantly shorter in combined treatment
      with DXZ9 and ryegrass compared to the control. The remediation was mostly due to
      degradation of the contaminants, as the net uptake of DDT and DDE by the ryegrass
      accounted for less than 3% of the total amount in the soil. DDT is reductively
      dechlorinated to DDD and dehydrochlorinated to DDE in the soil; the metabolites
      of DDE and DDD were multiple undefined substances. The toxicity of the soil was
      significantly reduced as a result of the treatment. The present study
      demonstrates that the bioremediation of soil contaminated with DDT and DDE by
      means of specific bacteria combined with ryegrass is feasible.

PMID- 29354857
TI  - Analytical characterization of products obtained from slow pyrolysis of
      Calophyllum inophyllum seed cake: study on performance and emission
      characteristics of direct injection diesel engine fuelled with bio-oil blends.
AB  - This paper aims to analyse the characteristics and properties of the fractions
      obtained from slow pyrolysis of non-edible seed cake of Calophyllum inophyllum
      (CI). The gas, bio-oil and biochar obtained from the pyrolysis carried out at 500
      degrees C in a fixed bed batch type reactor at a heating rate of 30  degrees
      C/min were characterized by various analytical techniques. Owing to the high
      volatile content of CI biomass (72.61%), it was selected as the raw material in
      this present investigation. GC-MS and FT-IR analysis of bio-oil showed the
      presence of higher amount of oxygenated compounds, phenol derivatives, esters,
      acid and furans. The physicochemical properties of the bio-oil were tested as per
      ASTM norms which imply that bio-oil is a highly viscous liquid with lower heating
      value as compared to that of diesel fuel. The chemical composition of evolved gas
      was analysed by using GC testing which revealed the presence of combustible
      components. The FT-IR characterization of biochar showed the presence of
      aliphatic and aromatic hydrocarbons whereas the elevated amount of carbon in
      biochar indicates its potential to be used as solid fuel. The performance and
      emission characteristics of CI engine were assessed with different CI bio-oil
      blends and compared with baseline diesel fuel. The results showed that addition
      of bio-oil leads to decreased brake thermal efficiency and increased brake
      specific energy consumption. Meanwhile, increase in blend ratio reduces harmful
      pollutants such as oxides of nitrogen and smoke in the exhaust. From the engine
      testing, it is suggested to employ 20% of CI bio-oil blends in CI engine to
      obtain better operation.

PMID- 29354858
TI  - Oil mixing behavior after an oil spill: identification conflicts of different
      fingerprints.
AB  - Clearing up whether spilled oil is mixed or not can strengthen the accuracy of
      oil spill identification. In the present study, the biomarkers in spilled oil
      samples were detected. The weathering modes of different types of diagnostic
      ratio and carbon isotope values of individual n-alkanes were also analyzed. The
      results showed that the diagnostic ratios of steroids, terpenes and aromatics,
      and weathering characteristics of carbon isotope composition (delta13C) of
      individual n-alkanes supported the idea that Dalian oil spill emerged from a
      single oil source. Furthermore, commonly used diagnostic ratios of n-alkanes
      indicated that the Dalian oil spill had undergone the oil mixing process. The
      different identifying outcomes indicate that some kinds of n-alkane-rich
      substance (such as oil dispersants) were mixed in the Dalian spilled oil and
      interfered with the routine diagnosis ratios of n-alkanes.

PMID- 29354861
TI  - Access to and Use of Psychiatric Services by Migrants Resettled in Northern
      Italy.
AB  - The present study was conducted to describe access to and use of psychiatric
      services by migrants resettled in a large and well-defined catchment area. The
      study was conducted in a catchment area of 459,536 inhabitants in Verona, a city
      located in the Northeast of Italy. Using a psychiatric case register, all native
      and migrant individuals with a first ever psychiatric contact from 2000 to 2015
      were identified. Service use data during the 12 months following first contact
      were collected. During the study period a total of 2610 migrants and 28,860
      natives had at least one psychiatric contact. A progressive rise in the
      proportion of migrants seeking psychiatric care was observed, from 2.5% in 2000
      to more than 14% in 2015. During the 12 months following first contact, the
      proportion of patients with a single consultation did not differ between
      resettled migrants and natives. However, migrants were more often marked users or
      heavy users of psychiatric services. Multivariate linear regression analyses
      showed that younger male individuals with psychotic disorders experienced higher
      psychiatric services use regardless their native or migrant condition. In a large
      catchment area with a well-developed community-based system of mental health care
      a progressive rise in the number of migrants seeking psychiatric care was
      observed. The pattern of service use during the 12 months after first contact was
      not related to nationality, suggesting the capacity of community psychiatric
      services to retain people in care. These findings call for the development of
      culturally and linguistically appropriate community psychiatric services.

PMID- 29354862
TI  - Luigi Porta's contribution to anesthesia in Europe in the 1800s.
AB  - Luigi Porta (1800-1875), an Italian physician who was well known in the field of
      surgery, played an important role in spreading ethereal anesthesia in Europe.
      Moreover, he proposed an original method to administer ethereal anesthesia, the
      Italian method "of the bladder of pig". This paper reminds us of the important
      role that this physician played in Anesthesiology.

PMID- 29354863
TI  - A minimal mechanics model for mechanosensing of substrate rigidity gradient in
      durotaxis.
AB  - Durotaxis refers to the phenomenon in which cells can sense the spatial gradient
      of the substrate rigidity in the process of cell migration. A conceptual two-part
      theory consisting of the focal adhesion force generation and mechanotransduction
      has been proposed previously by Lo et al. to explain the mechanism underlying
      durotaxis. In the present work, we are concerned with the first part of the
      theory: how exactly is the larger focal adhesion force generated in the part of
      the cell adhering to the stiffer region of the substrate? Using a simple
      elasticity model and by assuming the cell adheres to the substrate continuously
      underneath the whole cell body, we show that the mechanics principle of static
      equilibrium alone is sufficient to account for the generation of the larger
      traction stress on the stiffer region of the substrate. We believe that our model
      presents a simple mechanistic understanding of mechanosensing of substrate
      stiffness gradient at the cellular scale, which can be incorporated in more
      sophisticated mechanobiochemical models to address complex problems in
      mechanobiology and bioengineering.

PMID- 29354864
TI  - Effect of the carbon dioxide 10,600-nm laser and topical fluoride gel application
      on enamel microstructure and microhardness after acid challenge: an in vitro
      study.
AB  - The aim of this in-vitro study was to evaluate positive effects of the carbon
      dioxide laser (CO2, 10,600 nm) with acidulated phosphate fluoride (APF) gel on
      enamel acid resistance. Twenty extracted human third molars (40 surfaces) were
      randomly assigned into four groups: group C, untreated control; group L, CO2
      laser alone group; group F, APF 1.23% fluoride gel; and group FL, APF 1.23% gel
      and laser. Samples from group L were irradiated with a CO2 laser for 30s. The
      parameter settings used were average power, 0.73 W; time on, 100 MUs; time off,
      40 ms; tip-to-tissue distance, 20 mm; tip diameter 700 MUm; and energy density
      with movements, 5 J/cm2. Samples from group F were treated with the APF gel for 4
      min, and the gel was washed off with distilled water. The enamel samples from
      group FL were treated with APF gel for 4 min and then irradiated with the CO2
      laser for 30s without removing the gel. Each enamel sample was placed in 50 ml
      soft drink (pH = 2.75) for 10 min then rinsed with deionized water and stored in
      artificial saliva at 37  degrees C for 1 h. Samples were assessed for Vickers
      hardness number (VHN) before and after treatments and subjected to SEM analysis.
      Data were analyzed using a one-way analysis of variance (ANOVA) and Tukey's test
      (alpha < 0.05). After the acid challenge, the untreated C group was demineralized
      to a great extent and the enamel surface was with the lowest mean score of
      microhardness. The observed VHN in the control (C group) had a mean value of
      176.13, the scores in the CO2 laser group (L group) were with mean value of
      238.40, the F group with a mean value of 218.45, and the fluoride-treated and
      laser-irradiated FL group-with a mean of 268.28 VHN. Paired t test performed to
      compare groups C, L, F, and FL has shown that group FL has greater resistance to
      decrease in microhardness of dental enamel (P <= 0.05) on exposure to acidic
      protocol. After the acid challenge, the fluoride-treated and laser-irradiated
      samples (group FL) showed the least diminution in enamel surface microhardness.
      The sub-ablative carbon dioxide laser irradiation in combination with fluoride
      treatment is more effective in protecting enamel surface and resisting
      demineralization than CO2 laser irradiation or fluoride alone.

PMID- 29354865
TI  - Age-, gender- and Arbeitsgemeinschaft fur Osteosynthesefragen type-specific
      clinical characters of adult tibial plateau fractures in eighty three hospitals
      in China.
AB  - OBJECTIVE: The purpose of this study was to verify the age-, gender- and
      Arbeitsgemeinschaft fur Osteosynthesefragen (AO) type-specific clinical
      characters of adult tibial plateau fractures in 83 hospitals in China and to
      investigate whether altitude has potential relationships with adult tibial
      plateau fractures. METHODS: A retrospective investigation was performed on
      consecutive patients with tibial plateau fractures treated in 83 hospitals in
      China between January 2010 and December 2011, data including age, gender and
      imaging were collected retrospectively through the PACS system and case reports
      checking system, imaging were classified into six types under fully qualified
      estimation based on AO classification. To further investigate imparities among
      different altitudes in China, all data were classified into four groups according
      to the centre altitudes of each city, G1 = plains group (<500 m), G2 = hills
      group (500-1000 m), G3 = mountain areas group (1000-2000 m), and G4 = plateau
      group (>2000 m). Comparison of gender distribution, age distribution and AO type
      were done. RESULTS: A total of 6,227 adult tibial plateau fractures were
      included. Men in the age range of 40-44 years were the most affected patients,
      and the overall high-risk injury type was 44-B. In four groups, the same peak age
      showed, namely, 40-44 years in males and 55-59 years in females. Age distribution
      showed no statistically significant difference in four groups (P > 0.05), while
      sex distribution and AO type indicated statistically significant differences (P <
      0.05). Note an inversion of sex ratio among people over 60 years. CONCLUSION: Our
      study showed that men in the 40-44 year age range are the most affected patients,
      and different sex distribution as well as injury type of adult tibial plateau
      fractures differed with various altitudes in China.

PMID- 29354866
TI  - Congenital anomalies of the limbs in mythology and antiquity.
AB  - Congenital anomalies of the limbs have been observed since ancient human
      civilizations, capturing the imagination of ancient physicians and people. The
      knowledge of the era could not possibly theorize on the biologic aspects of these
      anomalies; however, from the very beginning of civilization the spiritual status
      of people attempted to find a logical explanation for the existence of such
      cases. The next logical step of the spiritual and religious system of the
      ancients was to correlate these anomalies with the Gods and to attribute them to
      a different level of existence in order to rationalize their existence. In these
      settings, the mythology and religious beliefs of ancient civilizations comprised
      several creatures that were related to the observed congenital anomalies in
      humans. The purpose of this historic review is to summarize the depiction of
      congenital anomalies of the limbs in mythology and antiquity, to present several
      mythological creatures with resemblance to humans with congenital anomalies of
      the limbs, to present the atmosphere of the era concerning the congenital
      anomalies, and to theorize on the anomaly and medical explanation upon which such
      creatures were depicted. Our aim is to put historic information in one place,
      creating a comprehensive review that the curious reader would find interesting
      and enjoyable.

PMID- 29354867
TI  - Short- and long-term outcomes of surgical management of peptic ulcer
      complications in the era of proton pump inhibitors.
AB  - PURPOSE: We evaluated the short-term and long-term outcomes of emergency
      operations for peptic ulcer (PUD) complications in a period of time in which the
      need for surgery is infrequent. METHODS: Retrospective review of operated
      patients (2007-2015) in one medical center. RESULTS: 81 patients were included
      (8.9 patients/year): 70 (86.4%) male; 11 (13.6%) female. Indications for
      operation were hemorrhage in 18 (22.2%), perforation in 62 (76.5%) and gastric
      outlet obstruction in one (1.2%). Only 16 (19.8%) operations included a procedure
      to reduce gastric acid secretion. Six (7.4%) patients had a second operation for
      recurrent or persistent complication. Of these, two had a procedure to reduce
      gastric acid secretion in their first operation. 16 (19.8%) patients died during
      the index hospitalization. Three (3.7%) patients were rehospitalized for a PUD
      complication following 3-24 months. One patient, who had surgery for a second
      perforation 3 months following the first operation, was treated empirically for
      Helicobacter Pylori (HP) between the two operations. In comparison to
      perforation, patients with hemorrhage were older (69.9 +/- 20.3 vs. 52.1 +/- 19.9
      years; p = 0.0015), more commonly had a history of PUD or treatment by
      nonsteroidal anti-inflammotry drugs (55.6 vs. 19.4%; p = 0.0054), more commonly
      had a procedure to reduce gastric acid secretion during their index operation
      (61.1 vs. 6.5%; p < 0.0001), and had a higher mortality (38.9 vs. 14.5%; p =
      0.0406). CONCLUSIONS: Mortality is high following surgery for the complications
      of PUD, moreso in patients undergoing surgery for hemorrhage. Reoperations and
      repeated hospitalizations for complications are not uncommon, even in patients
      who have had procedures to reduce gastric acid secretion and HP eradication.

PMID- 29354869
TI  - Organ donor pancreases for the study of human islet cell histology and
      pathophysiology: a precious and valuable resource.
AB  - Direct in vivo assessment of pancreatic islet-cells for the study of the
      pathophysiology of diabetes in humans is hampered by anatomical and technological
      hurdles. To date, most of the information that has been generated is derived from
      histological studies performed on pancreatic tissue from autopsy, surgery, in
      vivo biopsy or organ donation. Each approach has its advantages and disadvantages
      (as summarised in this commentary); however, in this edition of Diabetologia,
      Kusmartseva et al ( https://doi.org/10.1007/s00125-017-4494-x ) provide further
      evidence to support the use of organ donor pancreases for the study of human
      diabetes. They show that length of terminal hospitalisation of organ donors prior
      to death does not seem to influence the frequency of inflammatory cells
      infiltrating the pancreas and the replication of beta cells. These findings are
      reassuring, demonstrating the reliability of this precious and valuable resource
      for human islet cells research.

PMID- 29354870
TI  - Knowledge and Practice of Oral Cancer Screening in Teaching Faculty-Comparison of
      Specialty and Year of Clinical Experience.
AB  - The purpose of this study was to assess the knowledge, practice, confidence, and
      perceived barriers to oral cancer screening among teaching faculty in Japan.
      Results were compared by specialist as well as years of clinical experience. A 25
      question survey was used to assess the oral cancer screening practices of faculty
      dentists at Iwate Medical University, School of Dental Medicine, the only dental
      school located in the northeast (Tohoku) region of Japan. The study was approved
      by the Institutional Review Board of Iwate Medical University. The response rate
      was 83% (n = 110, 71.8% were male). This survey revealed that only 43.6% of the
      dentists performed oral cancer screening frequently (always or usually) at the
      initial appointment, and there was no significant differences between specialists
      and clinical experience. Visual inspection of the oral cavity was the primary
      screening method, but the frequency and content of the examination (TMJ and
      tonsil) was significantly different between specialties. A history of cancer and
      tobacco use motivated providers to perform an examination and was significantly
      different between various specialists and clinically experienced providers. In
      contrast, HPV and alcohol consumption were a weak motivator. The confidence level
      of providers on their examination knowledge/skills was poor, especially among
      junior faculty. More than 80% of junior faculty indicated a lack of
      knowledge/skills as a major barrier.

PMID- 29354872
TI  - Self-administered nicotine increases fat metabolism and suppresses weight gain in
      male rats.
AB  - RATIONALE: The ability of nicotine to suppress body weight is cited as a factor
      impacting smoking initiation and the failure to quit. Self-administered nicotine
      in male rats suppresses weight independent of food intake, suggesting that
      nicotine increases energy expenditure. OBJECTIVE: The current experiment
      evaluated the impact of self-administered nicotine on metabolism in rats using
      indirect calorimetry and body composition analysis. METHODS: Adult male rats with
      ad libitum access to powdered standard rodent chow self-administered intravenous
      infusions of nicotine (60 MUg/kg/infusion or saline control) in daily 1-h
      sessions in the last hour of the light cycle. Indirect calorimetry measured
      respiratory exchange ratio (RER), energy expenditure, motor activity, and food
      and water consumption for 22.5 h between select self-administration sessions.
      RESULTS: Self-administered nicotine suppressed weight gain and reduced the
      percent of body fat without altering the percent of lean mass, as measured by
      Echo MRI. Nicotine reduced RER, indicating increased fat utilization; this effect
      was observed prior to weight suppression. Moreover, nicotine intake did not
      affect motor activity or energy expenditure. Daily food intake was not altered by
      nicotine self-administration; however, a trend in suppression of meal size, a
      transient suppression of water intake, and an increase in meal frequency was
      observed. CONCLUSION: These data provide evidence that self-administered nicotine
      suppresses body weight via increased fat metabolism, independent of significant
      changes in feeding, activity, or energy expenditure.

PMID- 29354871
TI  - Assessing uncertainty in annual nitrogen, phosphorus, and suspended sediment load
      estimates in three agricultural streams using a 21-year dataset.
AB  - Accurate estimation of constituent loads is important for studies of ecosystem
      mass balance or total maximum daily loads. In response, there has been an effort
      to develop methods to increase both accuracy and precision of constituent load
      estimates. The relationship between constituent concentration and stream
      discharge is often complicated, potentially leading to high uncertainty in load
      estimates for certain constituents, especially at longer-term (annual) scales. We
      used the loadflex R package to compare uncertainty in annual load estimates from
      concentration vs. discharge relationships in constituents of interest in
      agricultural systems, including ammonium as nitrogen (NH4-N), nitrate as nitrogen
      (NO3-N), soluble reactive phosphorus (SRP), and suspended sediments (SS). We
      predicted that uncertainty would be greatest in NO3-N and SS due to complex
      relationships between constituent concentration and discharge. We also predicted
      lower uncertainty with a composite method compared to regression or interpolation
      methods. Contrary to predictions, we observed the lowest uncertainty in annual
      NO3-N load estimates (relative error 1.5-23%); however, uncertainty was greatest
      in SS load estimates, consistent with predictions (relative error 19-96%). For
      all constituents, we also generally observed reductions in uncertainty by up to
      34% using the composite method compared to regression and interpolation
      approaches, as predicted. These results highlight differences in uncertainty
      among different constituents and will aid in model selection for future studies
      requiring accurate and precise estimates of constituent load.

PMID- 29354875
TI  - A parsimonious model of brightness induction.
AB  - We present a parsimonious model of brightness induction which can account for
      various brightness illusions of both brightness-contrast and brightness
      assimilation types. Our model is based on a difference of difference-of-Gaussian
      filter and a two-pass model of attentive vision based on the parallel channels in
      the central visual pathway. It overcomes some of the problems that could not be
      addressed by the well-known oriented difference of Gaussian model like those
      associated with Mach band and checkerboard illusions. This model attempts to
      provide insight to the mechanism of attention in brightness perception through
      the two major complimentary visual channels, viz. the magnocellular and the
      parvocellular.

PMID- 29354873
TI  - Clinical characteristics associated with subcutaneous tophi formation in Chinese
      gout patients: a retrospective study.
AB  - The objective of this study is to analyze clinical characteristics associated
      with the formation of subcutaneous tophi among Chinese gout patients. It was a
      retrospective outpatient cohort study. Five thousand six hundred ninety-three
      gout patients treated at the Affiliated Hospital of Qingdao University from March
      2011 to February 2016 were included and divided into the tophus group and non
      tophus group according to the presence of megascopic tophus. Relevant clinical
      information and biochemical parameters were analyzed to identify potential risk
      factors for the incidence of subcutaneous tophi. There are significant difference
      (P < 0.05) between the tophus and non-tophus groups in gender, family history,
      exercise, incidence of obesity, hypertension, renal dysfunction, kidney stone,
      coronary heart disease, and upper limb joint involvement. Between the two groups,
      significant difference (P < 0.01) was detected in the onset age (43.80 +/- 13.82
      years vs. 45.40 +/- 13.77 years), duration of disease (10.28 +/- 7.54 years vs.
      5.11 +/- 6.06 years), number of joint involved (3.11 +/- 2.15 vs. 1.81 +/- 1.35),
      systolic pressure (138.53 +/- 19.46 mmHg vs. 133.87 +/- 17.93 mmHg), diastolic
      pressure (89.55 +/- 12.73 mmHg vs. 87.48 +/- 11.77 mmHg), serum uric acid (487.15
      +/- 120.13 MUmol/L vs. 458.89 +/- 119.04 MUmol/L), creatinine (93.87 +/- 54.19
      MUmol/L vs. 85.51 +/- 37.71 MUmol/L), and creatinine clearance rate (Ccr) (93.05
      +/- 48.7 mL/min vs. 106.61 +/- 51.76 mL/min). Logistic regression analysis
      suggests that duration of disease, number of joints involved, involvement of
      upper limb joints, kidney stones, diastolic pressure, and serum uric acid are
      associated with the subcutaneous tophi formation, while exercise and obesity are
      protective factors. The present study has identified several clinical parameters
      (such as duration of disease, involvement of upper limb joints, involved joints,
      kidney stone, hypertension) as risk factors for the incidence of subcutaneous
      tophi, which provides insights into the treatment and prevention of tophus.

PMID- 29354876
TI  - Evaluating Treatment Patterns for Small Cell Carcinoma of the Colon Using the
      National Cancer Database (NCDB).
AB  - OBJECTIVE(S): The objective of this study was to characterize the
      clinicopathological prognostic factors and treatment patterns for small cell
      carcinoma (SCC) of the colon, a rare disease without standard treatment
      guidelines. METHODS: We analyzed clinicopathological and treatment variables for
      503 cases of histologically proven SCC colon entered into the National Cancer
      Database (NCDB) between 2004 and 2013. Survival curves were generated using
      Kaplan-Meier and compared by the log-rank test. Cox proportional hazard
      regression was used to control for covariates and evaluate the effect of
      different treatment modalities on overall survival. RESULTS: Four hundred seventy
      two (93.8%) patients had complete clinical staging information and were therefore
      included in our analysis. Of these patients, 149 (31.5%) had limited stage
      disease (LD) and 323 (68.4%) had extensive stage disease (ED) at presentation.
      Median overall survival (OS) for patients with ED was significantly lower than
      for those with LD (4.04 months vs. 21.82 months; p < 0.001). Multivariate Cox
      regression analysis showed administration of chemotherapy was associated with
      improved survival in patients with LD and ED (p = 0.026, p < 0.001) while surgery
      was not associated with improved survival in patients with LD or ED (p = 0.943, p
      = 0.630). Radiation therapy was associated with improved survival in patients
      with ED (p = 0.044). CONCLUSIONS: SCC of the colon carries a poor prognosis,
      especially in patients presenting with metastatic disease. Surgery and
      chemotherapy are administered more frequently than radiation, and chemotherapy is
      associated with improved survival, unlike surgery.

PMID- 29354877
TI  - Outcomes of Radioembolization in Patients with Chemorefractory Colorectal Cancer
      Liver Metastasis: a Single-Center Experience.
AB  - PURPOSE: We aimed to evaluate the efficacy and outcomes of radioembolization with
      Yttrium-90 (Y-90) microspheres in patients with unresectable and chemorefractory
      colorectal cancer liver metastasis (CRCLM). METHODS: This single-center study
      included 43 patients (34 male, 9 female) who underwent radioembolization with Y
      90 for unresectable, chemorefractory CRCLM between September 2008 and July 2014.
      Overall survival (OS), liver progression-free survival (LPFS), overall response
      rate (ORR), local disease control rate (LDCR), and relations of these parameters
      with patient disease characteristics were evaluated. OS and LPFS rates were
      compared according to microspheres. Survival rates were calculated with Kaplan
      Meier method, and potential prognostic variables were evaluated on univariate
      analyses. RESULTS: Post-procedural median OS was 12.8 months. LPFS was 5.6
      months. ORR was 33%, LDCR was 67% on 3rd month follow-up. Low tumor burden (<
      25%) was associated with higher median OS after radioembolization (< 25 vs > 25
      50% p < 0.0001 and < 25 vs > 50% p = 0.005). Patients with left colon tumors
      exhibited significantly longer median OS after metastasis than right colon tumors
      (p = 0.046). Extrahepatic disease and synchronicity showed poorer survival
      parameters; however, the difference was not significant (p = 0.1 and p = 0.3,
      respectively). In subgroup analyses, the distribution of patient number and
      characteristics showed heterogeneity as number of patients with low tumor burden
      was higher in resin Y-90 group. Resin Y-90 group exhibited significantly higher
      median OS and LPFS compared to glass Y-90 group (16.5 vs. 7 months, p = 0.001;
      6.73 vs. 3.38 months, p = 0.023, respectively). CONCLUSION: Radioembolization is
      a safe local-regional treatment option in chemorefractory, inoperable CRCLM.
      Radioembolization at earlier stages may lead to more favorable results especially
      with lower tumor burden patients.

PMID- 29354878
TI  - Relative effects of genetic variation sensu lato and sexual dimorphism on plant
      traits and associated arthropod communities.
AB  - Intraspecific plant trait variation can have cascading effects on plant
      associated biotic communities. Sexual dimorphism is an important axis of genetic
      variation in dioecious plants, but the strength of such effects and the
      underlying mechanisms relative to genetic variation are unknown. We established a
      common garden with 39 genotypes of Baccharis salicifolia sampled from a single
      population that included male and female genotypes and measured plant traits and
      quantified associated arthropod communities. Genetic variation sensu lato
      (genotypic variation) had strong effects on most plant traits (flower number,
      relative growth rate, specific leaf area, percent water content, carbon-nitrogen
      ratio, monoterpene but not sesquiterpene concentrations) and on herbivore and
      predator density, and on arthropod community composition (relative abundance of
      14 orders). In contrast, sexual dimorphism had weaker effects on only a few plant
      traits (flower number and relative growth rate), on predator density, and on
      arthropod community composition, but had no effect on herbivore density.
      Variation in flower number drove genetic variation sensu lato and sex dimorphism
      in predator density and arthropod community composition. There was unique genetic
      variation sensu lato in herbivore density (positively) associated with
      monoterpene concentration and in arthropod community composition associated with
      specific leaf area and carbon-nitrogen ratio. There was unique sexual dimorphism
      in arthropod community composition associated with plant relative growth rate.
      Together, these results demonstrate that genetic variation sensu lato and sexual
      dimorphism can shape plant-associated arthropod communities via both parallel and
      unique mechanisms, with greater overall effects of the former.

PMID- 29354879
TI  - Metagenomic Signatures of Microbial Communities in Deep-Sea Hydrothermal
      Sediments of Azores Vent Fields.
AB  - The organisms inhabiting the deep-seafloor are known to play a crucial role in
      global biogeochemical cycles. Chemolithoautotrophic prokaryotes, which produce
      biomass from single carbon molecules, constitute the primary source of nutrition
      for the higher organisms, being critical for the sustainability of food webs and
      overall life in the deep-sea hydrothermal ecosystems. The present study
      investigates the metabolic profiles of chemolithoautotrophs inhabiting the
      sediments of Menez Gwen and Rainbow deep-sea vent fields, in the Mid-Atlantic
      Ridge. Differences in the microbial community structure might be reflecting the
      distinct depth, geology, and distance from vent of the studied sediments. A
      metagenomic sequencing approach was conducted to characterize the microbiome of
      the deep-sea hydrothermal sediments and the relevant metabolic pathways used by
      microbes. Both Menez Gwen and Rainbow metagenomes contained a significant number
      of genes involved in carbon fixation, revealing the largely autotrophic
      communities thriving in both sites. Carbon fixation at Menez Gwen site was
      predicted to occur mainly via the reductive tricarboxylic acid cycle, likely
      reflecting the dominance of sulfur-oxidizing Epsilonproteobacteria at this site,
      while different autotrophic pathways were identified at Rainbow site, in
      particular the Calvin-Benson-Bassham cycle. Chemolithotrophy appeared to be
      primarily driven by the oxidation of reduced sulfur compounds, whether through
      the SOX-dependent pathway at Menez Gwen site or through reverse sulfate reduction
      at Rainbow site. Other energy-yielding processes, such as methane, nitrite, or
      ammonia oxidation, were also detected but presumably contributing less to
      chemolithoautotrophy. This work furthers our knowledge of the microbial ecology
      of deep-sea hydrothermal sediments and represents an important repository of
      novel genes with potential biotechnological interest.

PMID- 29354880
TI  - Endothelin-1-induced hypertrophic alterations and heme oxygenase-1 expression in
      cardiomyoblasts are counteracted by beta estradiol: in vitro and in vivo studies.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor normally active in maintaining
      vascular tone, may mediate significant pathogenic effects, contributing to
      several serious diseases when aberrantly expressed or regulated. The present
      study evaluates the capacity of ET-1 to affect endothelin-1-associated
      hypertrophic activity and decreased expression of heme oxygenase-1 by H9c2 rat
      cardiomyoblasts in vitro, corresponding to in vivo processes underlying
      cardiovascular diseases (CVDs). Beta estradiol (beta-E) is tested for its
      capacity to alter the effects of ET-1. H9c2 cells, cultured 48 h, were stimulated
      with 100-10,000 nM of ET-1 and evaluated for changes in cell size, cell
      viability, and expression of the cytoprotective heat shock protein heme oxygenase
      1 (HO-1), with 200 nM of beta-E included in selected cultures to evaluate its
      effect on ET-1-mediated changes. The application of 100 to 10,000 nM of ET-1
      resulted in a significant increase in average cell size and decreases in both
      cell viability and HO-1 protein content (p < 0.05). Moreover, 200 nM of beta-E
      was observed to significantly counteract these effects by cardiomyoblasts
      stimulated with 1000 nM of ET-1 (p < 0.05). Sprague-Dawley rats treated
      intravenously with 1000 ng/kg of ET-1 demonstrated reduced HO-1 expression in
      peripheral blood and left ventricular tissue, which was counteracted by injection
      of 200 ng/kg beta-E-demonstrating a possible correspondence between in vitro and
      in vivo effects. An outcome of particular value for clinical use of beta-E, in
      the management of cardiac hypertrophy, is the observed capacity of the drug to
      abate ET-1-mediated suppression of HO-1 expression. It has been previously
      demonstrated that HO-1 inducers exhibit potent cardioprotective properties, thus
      offering the promise of combining them with beta-E, allowing lower effective
      dosage of the drug and concomitantly lower adverse side effects associated with
      its clinical use. Major findings of this investigation are that pretreatment of
      cardiomyoblasts with beta-E inhibited their hypertrophic response to ET-1 and
      counteracts the decrease of cell viability. These effects were associated with a
      restoration of HO-1 protein expression in both under in vitro and in vivo
      conditions.

PMID- 29354881
TI  - Cell shape can be uncoupled from formononetin induction in a novel cell line from
      Callerya speciosa.
AB  - KEY MESSAGE: It is the first time that formononetin produced by cell culture and
      its accumulation was shown to be triggered by specific stress signalling linked
      jasmonate pathway. Callerya speciosa, an endangered traditional Chinese medicine
      plant, is intensively used in traditional folk medicine. To develop sustainable
      alternatives for the overexploitation of natural resources, a suspension cell
      line was created from C. speciosa. Ingredients of C. speciosa, for instance the
      isoflavone formononetin, are formed during a peculiar swelling response of the
      root, which is considered as a quality trait for commercial application. A cell
      strain with elongated cells was obtained by using synthetic cytokinin 6
      benzylaminopurine (6-BA) and synthetic auxin picloram. Both, picloram and 6-BA,
      promote cell division, whereas picloram was shown to be crucial for the
      maintenance of axial cell expansion. We addressed the question, whether the loss
      of axiality observed in the maturating root is necessary and sufficient for the
      accumulation of formononetin. While we were able to mimic a loss of axiality for
      cell expansion, either by specific combinations of 6-BA and picloram, or by
      treatment with the anti-microtubular compound oryzalin, formononetin was not
      detectable. However, formononetin could be induced by the stress hormone methyl
      jasmonate (MeJA), as well as by the bacterial elicitor flagellin peptide (flg22),
      but not by a necrosis inducing protein. Combined the fact that none of these
      treatments induced the loss of axiality, we conclude that formononetin
      accumulates in response to basal defence and unrelated with cell swelling.

PMID- 29354882
TI  - Correction to: Simultaneous detection of periodontal pathogens in subgingival
      plaque and placenta of women with hypertension in pregnancy.
AB  - The original version of this article unfortunately contained a mistake. Ambika
      Devi K was not listed among the authors. The corrected authorship is given below.

PMID- 29354883
TI  - Prevalence of technical errors and periapical lesions in a sample of
      endodontically treated teeth: a CBCT analysis.
AB  - OBJECTIVES: The aims of this study are to identify the most frequent technical
      errors in endodontically treated teeth and to determine which root canals were
      most often associated with those errors, as well as to relate endodontic
      technical errors and the presence of coronal restorations with periapical status
      by means of cone-beam computed tomography images. METHODS: Six hundred eighteen
      endodontically treated teeth (1146 root canals) were evaluated for the quality of
      their endodontic treatment and for the presence of coronal restorations and
      periapical lesions. Each root canal was classified according to dental groups,
      and the endodontic technical errors were recorded. Chi-square's test and
      descriptive analyses were performed. RESULTS: Six hundred eighty root canals
      (59.3%) had periapical lesions. Maxillary molars and anterior teeth showed higher
      prevalence of periapical lesions (p < 0.05). Endodontic treatment quality and
      coronal restoration were associated with periapical status (p < 0.05).
      Underfilling was the most frequent technical error in all root canals, except for
      the second mesiobuccal root canal of maxillary molars and the distobuccal root
      canal of mandibular molars, which were non-filled in 78.4 and 30% of the cases,
      respectively. CONCLUSIONS: There is a high prevalence of apical radiolucencies,
      which increased in the presence of poor coronal restorations, endodontic
      technical errors, and when both conditions were concomitant. Underfilling was the
      most frequent technical error, followed by non-homogeneous and non-filled canals.
      CLINICAL RELEVANCE: Evaluation of endodontic treatment quality that considers
      every single root canal aims on warning dental practitioners of the prevalence of
      technical errors that could be avoided with careful treatment planning and
      execution.

PMID- 29354884
TI  - Quantitative evaluation of dental anxiety indicators in the serum and saliva
      samples of children treated under general anesthesia.
AB  - OBJECTIVES: Dental anxiety level has been previously associated with oral health
      status. Since general anesthesia (GA) allows dental treatments to be performed in
      anxious children with a high number of caries, we aimed to evaluate the dental
      anxiety levels of these children before and after dental treatments performed
      under GA. MATERIALS AND METHODS: Thirty-eight children with high anxiety aged
      between 35 and 72 months who required multiple dental treatments to be performed
      under GA were included in the study. Frankl's Behavior Rating Scale, sitting
      patterns, Facial Image Scale, and Children's Fear Survey Schedule-Dental Subscale
      (completed by the children's parents) were recorded before and after the dental
      treatments performed under GA. Pre-treatment and post-treatment biochemical
      parameters, including cortisol, alpha-amylase, and chromogranin A levels, in
      saliva and serum samples were also evaluated. RESULTS: The psychometric scales
      showed a statistically significant reduction in the post-treatment dental anxiety
      levels of the children compared with the pre-treatment anxiety levels.
      Additionally, the biochemical parameters measured in the serum and whole saliva
      samples showed a decrease after treatments performed under GA. CONCLUSIONS: Our
      study results suggest that performing dental treatments under GA can reduce the
      dental anxiety levels of children with a high number of caries.

PMID- 29354885
TI  - Neuronal loss and gliosis in the rat striatum subjected to 15 and 30 minutes of
      middle cerebral artery occlusion.
AB  - Selective neuronal death or loss in certain brain regions has been well
      characterized in animal models of transient global cerebral ischemia. However,
      selective neuronal death in transient focal cerebral ischemia needs more
      investigation. Therefore, in this study, we studied selective neuronal death in
      the striatum (caudate putamen) of rats subjected to 15 or 30 min middle cerebral
      artery occlusion (MCAO). Neuronal death occurred in the dorsolateral field, not
      in the medial field in 30 min, not 15 min, MCAO-operated rats 5 days after MCAO
      using neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B
      histofluorescence staining. In this group, immunoreactivity of glial fibrillary
      acidic protein in astrocytes was hardly shown in the dorsolateral field, although
      the immunoreactivity increased in the medial field. In addition, immunoreactivity
      of ionized calcium binding adapter molecule 1 in microglia was dramatically
      increased in the dorsolateral, not in the medial, field only in 30 min MCAO
      operated rats. Briefly, these results show that at least 30 min of MCAO can evoke
      selective neuronal death, astrocytic dysfunction and microglial activation in the
      dorsolateral field of the rat striatum and suggest that a rat model of 30 min
      MCAO can be used to investigate mechanisms of neuronal death and gliosis
      following brief transient focal cerebral ischemic events for acute transient
      ischemic attack.

PMID- 29354886
TI  - Growth performance, body composition, and digestive functionality of Senegalese
      sole (Solea senegalensis Kaup, 1858) juveniles fed diets including microalgae
      freeze-dried biomass.
AB  - Senegalese sole is one of the most promising fish species cultivated in the
      Southern European countries. This study was aimed at assessing the effects of
      microalgae biomass added to diets for Senegalese sole juveniles on fish growing
      and condition status. Three isoproteic (52%) and isolipidic (10%) were formulated
      containing 15% Tisochrysis lutea (TISO), Nannochloropsis gaditana (NAN), or
      Scenedesmus almeriensis (SCE) biomass, respectively. An experimental microalgae
      free diet (CT) and a commercial diet (COM) were used as controls. Fish were fed
      at 3% of their body weight for 85 days. Final body weight of fish fed microalgae
      supplemented diets did not differ from group fed CT diet. Fish-fed CT, TISO, NAN,
      and SCE showed higher growth performance and nutrient utilization figures than
      specimen-fed COM diet. The highest carcass lipid content was found in COM group
      (141 g kg-1), and no differences were observed in body protein content. Ash was
      significantly higher in TISO, NAN, and SCE groups compared to fish-fed CT. Muscle
      EPA and DHA contents were not modified owing to the different dietary treatments.
      The n3/n6 and EPA/DHA ratios in muscle were similar in all the experimental
      groups. The quantification of digestive proteolytic activities did not differ
      among experimental groups, although differences in the protease pattern in
      digestive extracts by zymography were revealed in those fish fed on COM diet.
      Both alpha-amylase activity in the intestinal lumen and leucine aminopeptidase in
      the intestinal tissue were significantly lower in COM fish. Specimens fed on SCE
      diet showed a higher leucine aminopeptidase activity associated to the intestinal
      tissue compared to NAN-fed fish (0.40 and 0.25 U g tissue-1, respectively). The
      ultrastructural study revealed that the dietary inclusion of algal biomass,
      especially T. lutea and N. gaditana, had a positive impact on the absorptive
      capacity of the intestinal mucosa. The highest values for the parameters
      microvilli length and microvilli absorption surface were observed in fish fed on
      NAN diet (1.99 MUm and 45.93 MUm2, respectively). Even though further studies
      aimed at optimizing commercial formulas for Senegalese sole are required prior to
      any large-scale practical utilization, the results obtained clearly suggest the
      potential of microalgae as dietary ingredients for this fish species.

PMID- 29354887
TI  - Delayed Recanalization Promotes Functional Recovery in Rats Following Permanent
      Middle Cerebral Artery Occlusion.
AB  - Most large vessel stroke patients have permanent occlusion, for which there are
      no current treatment options. Recent case studies have indicated delayed
      recanalization, that is recanalization outside of the 6-h treatment window, may
      lead to improved outcome. We hypothesized that delayed recanalization will
      restore cerebral blood flow, leading to improved function in rats. Male SD rats
      were subjected to pMCAO or sham surgery. Delayed recanalization was performed on
      either day 3, 7, or 14 after pMCAO in a subset of animals. Cerebral blood flow
      was monitored during suture insertion, during recanalization, and then at
      sacrifice. Neurological function was evaluated for 1 week after delayed
      recanalization and at 4 weeks post-ictus. After sacrifice, cerebral morphology
      was measured. Compared to no treatment, delayed recanalization restored cerebral
      blood flow, leading to sensorimotor recovery, improved learning and memory,
      reduced infarct volume, and increased neural stem/progenitor cells within the
      infarction. The data indicate that earlier delayed recanalization leads to better
      functional and histological recovery. Yet, even restoring cerebral blood flow 14
      days after pMCAO allows for rats to regain sensorimotor function. This
      exploratory study suggests that delayed recanalization may be a viable option for
      treatment of permanent large vessel stroke.

PMID- 29354888
TI  - Point-of-care hemoglobin testing for postmortem diagnosis of anemia.
AB  - An autopsy involves examination of a body using invasive methods such as
      dissection, and includes various tests using samples procured during dissection.
      During medicolegal autopsies, the blood carboxyhemoglobin concentration is
      commonly measured using the AVOXimeter(r) 4000 as a point-of-care test. When
      evaluating the body following hypovolemic shock, characteristics such as reduced
      livor mortis or an anemic appearance of the viscera can be identified, but these
      observations arequite subjective. Thus, a more objective test is required for the
      postmortem diagnosis of anemia. In the present study, the AVOXimeter(r) 4000 was
      used to investigate the utility of point-of-care hemoglobin testing. Hemoglobin
      tests were performed in 93 autopsy cases. The AVOXimeter(r) 4000 and the BC-2800
      Auto Hematology Analyzer were used to test identical samples in 29 of these
      cases. The results of hemoglobin tests performed with these two devices were
      statistically similar (r = 0.969). The results of hemoglobin tests using
      postmortem blood were compared with antemortem test results from medical records
      from 31 cases, and these results were similar. In 13 of 17 cases of death from
      internal hemorrhage, hemoglobin levels were lower in the cardiac blood than in
      blood from the affected body cavity, likely due to compensatory changes induced
      by antemortem hemorrhage. It is concluded that blood hemoglobin testing may be
      useful as a point-of-care test for diagnosing postmortem anemia.

PMID- 29354889
TI  - "My Invisalign experience": content, metrics and comment sentiment analysis of
      the most popular patient testimonials on YouTube.
AB  - BACKGROUND: The aim of the study was to investigate the popularity, content of
      Invisalign patient testimonials on YouTube, as well as the sentiment of the
      related comments. METHODS: Using the term "Invisalign experience," the top 100
      results on YouTube by view count were screened for English spoken patient videos
      that attracted comments. Video information (time since video upload,
      sponsorship), engagement metrics (comments, likes, dislikes, subscriptions), and
      views were collected. Videos were rated for information completeness (ICS), and
      comments were classified by origin and content. The emotional loading of the
      comments was measured using automated sentiment analysis. RESULTS: The 40
      reviewed testimonials scored an average ICS of 3.78 (SD 0.97). ICS, time since
      upload, and video duration did not appear to significantly influence the number
      of views, subscriptions, likes, dislikes, and comments. There was a statistically
      significant difference (P = 0.03) between mean positive (2.01, SD 0.95) and
      negative sentiment scores (- 1.90, SD 1.14). Commenter's status and overall
      comment on video were significantly associated with positive sentiment scores.
      There was a significant association between sponsorship, commenter's status,
      overall comment on video, focus of concern, perceived Invisalign's disadvantages,
      and increased negative sentiment scores. CONCLUSIONS: Engagement of audience and
      views of the most popular Invisalign patient testimonials were not significantly
      influenced by completeness of information, video duration, and lifespan. The
      sentiment of viewers' comments about Invisalign treatment was significantly more
      positive and was significantly associated with their status, content, and
      sponsorship of videos. Orthodontic trends on YouTube need to be cautiously
      monitored for planning interventions that improve patients' knowledge about
      orthodontics.

PMID- 29354890
TI  - Angular relational signature-based chest radiograph image view classification.
AB  - In a computer-aided diagnosis (CAD) system, especially for chest radiograph or
      chest X-ray (CXR) screening, CXR image view information is required.
      Automatically separating CXR image view, frontal and lateral can ease subsequent
      CXR screening process, since the techniques may not equally work for both views.
      We present a novel technique to classify frontal and lateral CXR images, where we
      introduce angular relational signature through force histogram to extract
      features and apply three different state-of-the-art classifiers: multi-layer
      perceptron, random forest, and support vector machine to make a decision. We
      validated our fully automatic technique on a set of 8100 images hosted by the
      U.S. National Library of Medicine (NLM), National Institutes of Health (NIH), and
      achieved an accuracy close to 100%. Our method outperforms the state-of-the-art
      methods in terms of processing time (less than or close to 2 s for the whole test
      data) while the accuracies can be compared, and therefore, it justifies its
      practicality. Graphical Abstract Interpreting chest X-ray (CXR) through the
      angular relational signature.

PMID- 29354891
TI  - [2107 hotspots review and future prospects in colorectal cancer].
AB  - Radical surgeries and(neo) adjuvant therapies have significantly prolonged
      survival of patients with colorectal cancer. Microinvasive surgery and function
      preservation become more important with the prerequisite of R0 resection. As for
      colorectal cancer, long term survival after laparoscopic curative surgery is
      proved non-inferior to its open counterpart. The new transanal approach of total
      mesorectal excision, while avoiding abdominal incision for extraction, may as
      well improve surgical quality. Local excision and the "watch and wait" strategy,
      though attractive for organ-preservation, are undermined by suboptimal clinical
      and radiographic assessment of lymph node and treatment response, respectively.
      Meanwhile, fresh changes are challenging long-established perioperative
      regiments. Shortening of adjuvant chemotherapy to 3 months reduces adverse events
      without compromising survival. Moving part of, or all, adjuvant courses to before
      surgery may improve response, thereby omitting protectomy or radiotherapy. To
      summarize, function preservation and quality of life has, together with survival,
      increasingly become the ultimate aim of colorectal cancer treatment, a field of
      constant evolvement.

PMID- 29354892
TI  - [2017 hotspots review and outlook on gastric cancer surgery in China].
AB  - The 12th International Gastric Cancer Congress (12th IGCC ) was successfully held
      in Beijing, China on 20th-23rd April, 2017, which gave Chinese surgeons a great
      opportunity to share clinical progress and experience in the surgical treatment
      of gastric cancer with colleagues from different countries. At the end of 2017,
      this article hereby reviews briefly the achievements of surgical work of gastric
      cancer, which was done by our Chinese surgeons in this year. Some aspects will be
      reviewed, aiming at summarizing experience, affirming achievement, finding out
      the gap and promoting improvement in the future. These aspects include the
      conversion therapy for stageIIII( gastric cancer; the minimally invasive surgery
      for gastric cancer; the alimentary tract reconstruction after gastrectomy;
      enhanced recovery after radical gastrectomy and surgery quality control and
      patient's quality of life after surgery. In 2017, the gastric cancer surgery in
      China has made some new progress in many fields, and some achievements have
      reached or are close to international advanced level. However, looking ahead to
      the coming year and the future, there are still some important works to be done
      in the field of clinical surgery for gastric cancer in China, which include (1)
      strengthening big clinical data in gastric cancer collection and analysis
      platform construction for the promotion of scientific decision in therapeutic
      strategy; (2) further participating in international academic exchange and
      cooperation with taking advantages of our big number of gastric cancer cases,
      great amount of bio-tissue samples and big number of professional surgeons to
      actively join the international clinical research and expand our academic
      influence in the world;(3)developing more multicentre prospective randomized
      controlled trials in order to further improve the scientific significance in
      Chinese clinical guideline, norms and expert consensus in surgical treatment for
      gastric cancer; (4) further improving effectiveness of the multidisciplinary team
      (MDT) model in order to truly play the role of each subject in resolving some
      difficult cases; (5) in terms of surgical treatment for patients, it should be
      continue to keep going on minimally invasive operation, rational perioperative
      treatment, refinement technique, radical cure resection, and to further improve
      operation quality control system, aiming at realizing both goals simultaneously
      in prolonging survival time and improving quality of life for the patients with
      gastric cancer.

PMID- 29354893
TI  - [Review of clinical investigation in minimally invasive gastrointestinal surgery
      in 2017 and future prospects].
AB  - Clinical investigation in minimally invasive gastrointestinal surgery has been
      developed by leaps and bounds in 2017. Standardizations of port placement,
      surgical approaches, lymphadenectomy, reconstruction, total laparoscopic surgery,
      incision-free technique, 3D laparoscope, as well as robotic surgeries, have been
      established. In the treatment for gastric cancer, the first-hand data of the
      laparoscopic technique for advanced gastric cancer will be released soon.
      Therefore, the research hotspots have been moved forward to lymphadenectomy,
      resection range, and reconstruction in laparoscopic advanced gastric cancer
      surgery. In the treatment for colorectal cancer, the lymphadenectomy range
      (complete colorectal excision and D3) and the effect of various of surgical
      approaches persistently become the research areas in laparoscopic colon cancer
      surgery. While the research interest of laparoscopic rectal cancer surgery still
      focus on the oncological effect evaluation of laparoscopic technique, duo to the
      recent evidence-based data challenging the usage of laparoscopic technique in
      rectal cancer treatment. What worth to notice is that trans-anal total mesorectal
      excision, as a new surgical approach, has undoubtedly become the most popular
      research field in 2017. Last but not least, the domestication of 3D instrument,
      laparoscope positioning robot, and surgical robot are the pop areas in the
      surgical instrument and equipment innovation area. In a word, with the 30-year
      development of minimally invasive surgery, represented by laparoscopic technique,
      it has become a mature technology, but still with some burning questions. The
      future trends of clinical investigations will focus on standardization of
      traditional laparoscopic techniques, development of new laparoscopic techniques,
      as well as the development of innovative digital equipments and instruments.

PMID- 29354894
TI  - [2017 hotspots review and future prospects of abdominal wall and hernia surgery].
AB  - Hernia and abdominal surgery keeps moving forward rapidly In 2017, lots of
      progress were achieved in etiology, material, and surgical technique. In
      etiology, TTN gene missense mutation was found in family members of indirect
      inguinal hernia. In material, a long-term slow-absorptive patch was present
      leading to a good choice of hernia therapy; application of 3D print for
      individual patch repair was expected. In surgical technique, efficacy of
      laparoscopic minimal invasive procedure or MILOS and eMILOS procedures was
      satisfactory in the treatment of complicated incisional hernia; tissue
      separation, patch placement and abdominal wall reconstruction by robotic surgery
      resulted in bigger operative space, faster postoperative recovery and lower
      morbidity of infection and seroma at operative site. In addition, there were more
      and more evidences to support that prophylactic use of patch in enterostomy can
      prevent the occurrence of postoperative parastomal hernia and incisional hernia.
      Domestic surgeons contributed mainly to the standardization of hernia surgery in
      2017. This article reviews the hotspots of hernia and abdominal wall surgery in
      2017, in the meantime, we prospect the progress in the near future.

PMID- 29354895
TI  - [Therapeutic evaluation and surgical strategy after neoadjuvant chemoradiotherapy
      for rectal cancer].
AB  - Neoadjuvant chemoradiotherapy for rectal cancer could significantly reduce the
      tumor stage, improve the radical resection and increase the overall survival rate
      of the patients. Recently researches reported that patients who acquired complete
      response after neoadjuvant chemoradiotherapy might accept "wait and see" strategy
      or local excision and could earn promising long-term outcomes as those accepted
      radical surgery. The diagnostic criteria and efficacy of tumor response for
      chemoradiotherapy are insufficient and controversial. Moreover, clinical practice
      showed that chemoradiotherapy-related surgical complications, including
      anastomotic leakage, incision complications and colon stricture, remarkably
      increased, so the benefits and risks of patients should be reconsidered further
      in choosing the surgical strategies after neoadjuvant chemoradiotherapy.

PMID- 29354896
TI  - [10-year series studies of chronic radiation proctopathy from The Sixth
      Affiliated Hospital of Sun Yat-sen University].
AB  - Chronic radiation proctopathy (CRP) is the delayed adverse effect after
      radiotherapy for pelvic malignancies. It is characterized as progressive fibrosis
      in pathology. The symptoms are usually unspecific which include rectal bleeding,
      perianal pain, tenesmus, stool frequencies and so on. The course of CRP can
      present from months to years after radiation. Severe complications can occur in
      the late stage and will greatly affect the quality of life. Currently, there is
      no standard guides for diagnosis and treatment of CRP. For advancing the
      knowledge and proposing new treatment modalities of CRP, this article summarizes
      our 10-year experience as follows: (1) Except the existence of vessel damage,
      interstitial fibrosis, mucous ulcer, edema and inflammatory cell infiltration in
      the radiation-injury area, the capillary count was obviously reduced in mucous
      substratum and angiostatin expression up-regulated remarkably in above area,
      resulting in the continuous development of compensatory capillary expansion and
      interstitial fibrosis in mucous layer. (2) Rectal ultrasound examination was used
      the first time to diagnose CRP. According to thickness change of rectal wall
      layer and increase of blood signal, severity of CRP activity was evaluated with
      good diagnostic value. (3) For slight-moderate rectal bleeding, moderate-heavy
      bleeding and heavy bleeding, application of retention enema with compound
      preparation based on mucoprotective agents, regional perfusion hemostasis with
      formaldehyde and proximal colostomy gained satisfactory efficacy. (4) Improved
      Parks operation should be recommended for CRP patients with advanced
      complications. (5) For rectal cancer patients receiving neoadjuvant
      chemoradiotherapy, "proximal extended excision" should be performed innovatively
      to decrease the risk of anastomotic complications (Tianhe Procedure).

PMID- 29354897
TI  - [Trend analysis of morbidity and mortality of colorectal cancer in China from
      1988 to 2009].
AB  - OBJECTIVE: To explore the trend change of the morbidity and mortality of
      colorectal cancer in China in order to provide reference to the prevention and
      control of colorectal cancer. METHODS: According to the 1-3 volumes of
      "Pathogenesis and death of malignancies in pilot program city and county of
      China", "Pathogenesis and death of cancer in China"(2003-2007) and "Registration
      annual report of tumor in China" published in 2011 and 2012, data of pathogenesis
      and death of colorectal cancer from 10 tumor registration spots, including
      Beijing urban, Shanghai urban, Wuhan urban, Harbin urban (defined as city urban),
      and Hebei Ci County, Jiangsu Qidong District, Zhejiang Jiashan District, Guangxi
      Fusui County, Fujian Changle District, Henan Lin County (defined as rural
      district), between 1988 and 2009 were collected. The morbidity and mortality were
      elucidated with world population standardized rate. Ratio of pathogenesis to
      death was calculated with crude rate of morbidity and mortality. Data of 22 years
      were enrolled into the linear regression analysis to calculate the annual change
      rate of morbidity and mortality statistically. RESULTS: (1) Colon cancer:
      morbidity presented increasing trend; male morbidity in city urban increased
      faster; mortality presented increasing trend as well; no significant difference
      of increasing velocity was observed between city urban and rural district;
      morbidity and mortality in city urban were higher compared to rural district;
      morbidity and mortality of males were higher compared to females; except stable
      Fujian Changle District, ratio of pathogenesis to death presented decreased trend
      in Shanghai urban and Hebei Ci County, and increased trend in other 7 spots (all
      P<0.05). (2) Rectal cancer: morbidity presented increasing trend, and its
      increasing velocity of city urban was faster compared to rural district;
      mortality presented decreased trend, especially in females, and this trend in
      rural district was worse compared to city urban; morbidity and mortality of males
      were higher compared to females, while no significant difference was observed
      between city urban and rural district; morbidity and mortality of males and
      females in Zhejiang Jiashan District were all decreased (all P<0.05); except
      stable Harbin city, ratio of pathogenesis to death presented increased trend in
      other 9 spots (all P<0.05). (3) Ratio analysis of morbidity and mortality showed
      that percentage of colon cancer increased gradually in all 10 spots between 1988
      2009. CONCLUSIONS: In the past 2 decades, the overall morbidity and mortality of
      colorectal cancer are higher in city urban and in male as compared with rural
      district and female. Colon cancer has higher morbidity than rectal cancer and its
      morbidity and mortality present increased trend, while morbidity of rectal cancer
      presents increased trend but its mortality presents decreased trend.

PMID- 29354898
TI  - [Clinicopathological characteristics and prognosis analysis of colorectal
      synchronous multiple primary cancer].
AB  - OBJECTIVE: To investigate the clinicopathological features and prognosis of
      colorectal synchronous multiple primary cancer(SMPC). METHODS: From January 2008
      to June 2011, 51 patients diagnosed with colorectal SMPC underwent surgery at
      Department of General Surgery of Peking University First Hospital. Their
      clinicopathological features, diagnosis, treatment and prognosis were summarized
      and analyzed. SMPC was diagnosed according to the following criteria: each tumor
      must have a definite pathologic picture of malignancy; metastasis or recurrence
      from another colorectal cancer was excluded; tumors must be distinctly separated
      by at least 5 cm of all intact bowel wall from each other; SMPC has abnormal
      cells between tumor and normal mucosa and abnormal gland of transitional zone;
      each cancer is infiltrating carcinoma except the carcinoma in situ; all the
      cancers are detected at the same time or within 6 months. Multiple primary
      colorectal cancer originated from familial colonic polyposis or ulcerative
      colitis was excluded. RESULTS: These 51 colorectal SMPC patients accounted for
      3.5% of 1 452 colorectal cancer patients in the same period at our hospital, with
      32 males and 19 females, and mean age of (63+/-13)(29 to 82) years. Of 51 cases,
      46(90.2%) had 2 original carcinoma, 3(5.9%) had 3 original carcinoma and 2(3.9%)
      had 4 carcinoma; 23(45.1%) complicated with colon polyps, 4(7.8%) complicated
      with malignancy outside the colorectum. In TNM staging, 7(13.7%), 15(29.4%),
      24(47.1%) and 5(9.8%) patients were stage I(, II(, III( and IIII( respectively.
      Among 51 patients undergoing surgery by different procedures, 16 were subtotal
      colon resection, 8 were extended right colon resection, 5 were extended left
      hemicolon resection, 8 were right hemicolon resection plus Dixon procedure, 10
      were Dixon, and 4 were right hemicolon resection plus sigmoid colon resection.
      Adjuvant chemotherapy and support treatment were given according to the condition
      after operation. A total of 105 tumors were found, including 25(23.8%) tumors in
      sigmoid colon, 24(22.9%) in rectum, 22(21.0%) in ascending colon and 4 in organs
      outside the colorectum. Tubular adenocarcinoma (86/105, 81.9%) was the main
      pathological type in these colorectal SMPC patients. During the follow-up of
      median 43.5 months, 10 cases presented local recurrence and 6 cases had liver
      metastasis. Multivariable analysis showed that <=65 years old (OR=22.757, 95%CI:
      1.562-331.543, P=0.002),undifferentiated carcinoma or mucous adenocarcinoma
      (OR=27.174, 95%CI: 2.834-260.512, P=0.004), stage III(-IIII( (OR=29.626, 95%CI:
      3.216-272.884, P=0.003) were independent risk factors of postoperative 5-year
      recurrence and metastasis, but the number of SMPC lesions and the surgical method
      were not associated with postoperative 5-year recurrence and metastasis (P=0.564,
      P=0.513). The 3-year and 5-year survival rates of colorectal SMPC patients were
      76.5% and 64.7%. CONCLUSION: Two-original carcinoma is the most common in
      colorectal SMPC patients, which mainly distributes in sigmoid colon and rectum.
      Postoperative monitoring should be strengthened for those patients with younger
      age, poor pathological types and advanced staging to prevent recurrence and
      metastasis.

PMID- 29354899
TI  - [Accurate low ligation of inferior mesenteric artery and root lymph node
      dissection according to different vascular typing in laparoscopic radical
      resection of rectal cancer].
AB  - OBJECTIVE: To explore the feasibility and clinical significance of precision low
      inferior mesenteric artery (IMA) ligation with the left colonic artery (LCA)
      preservation and root lymph node dissection in laparoscopic radical resection for
      rectal cancer, according to the inferior mesenteric artery (IMA) types. METHODS:
      One Hundred and fore cases of rectal cancer patients who underwent laparoscopic
      resection in The Sixth Affiliated Hospital of Sun Yat-sen University from October
      2015 to June 2016 were selected and divided into study group and control group
      according to different surgical methods. The study group (52 cases) accepted
      precision low IMA ligation with the LCA preservation and root lymph node (No.253)
      dissection, according to the IMA types and length examined by preoperative
      computed tomography angiography (CTA) reconstruction. The control group (52
      cases) accepted the traditional high IMA ligation. The perioperative efficacy
      indexes and postoperative recovery situation of the two groups were compared.
      RESULTS: The IMA types, IMA length and preoperative clinical stages were not
      significantly different between the two groups (all P>0.05). The surgery was
      completed smoothly for patients in both groups, with no conversion to open
      surgery. But two patients in the study group underwent left colonic artery
      ligation for intra-operative need. There were no significant differences in the
      operative time, intra-operative blood lose, the rate of protective ileostomy and
      post-operative pathological stages between the two groups (all P>0.05). More
      total lymph nodes [(24.9+/-5.7) vs. (16.9+/-4.2), P=0.001] and No.253 lymph nodes
      [(2.4+/-1.1) vs. (1.5+/-0.8), P=0.001] were harvested in study group as compared
      to control group. However, the positive rate of total harvested lymph nodes and
      No.253 lymph nodes between the two groups were not significantly different
      (P>0.05). There were no significant differences between the two groups in
      postoperative first anal exhaust time, postoperative hospital stay, total volume
      of postoperative intraperitoneal drainage, postoperative abdominal drainage tube
      retention time, postoperative anal drainage tube retention time and postoperative
      catheter retention time (All P>0.05). There were 2 cases of postoperative dysuria
      and 1 case of anastomotic bleeding in study group. There were 3 cases of
      postoperative dysuria and 2 cases of anastomotic leak in control group. Less
      postoperative complications (5.8% vs. 9.6%, P<0.05) in study group as compared to
      control group. There was no rehospitalization or death case in two groups within
      30 days after operation. CONCLUSIONS: In the laparoscopic radical resection of
      rectal cancer, preserving LCA and cleaning the root lymph nodes according to IMA
      types, which could increase the number of harvested lymph nodes and reduce the
      postoperative complications was safe and effective.

PMID- 29354900
TI  - [Analysis of risk factor of perioperative complications in patients with radical
      gastrectomy for gastric cancer and its influence on prognosis].
AB  - OBJECTIVE: To study the risk factor of perioperative complication in gastric
      cancer patients with radical therapy and its influence on prognosis. METHODS:
      Clinical, pathological and follow-up data of 1 148 gastric cancer patients
      undergoing radical gastrectomy at Tianjin Medical University Affiliated Tumor
      Hospital between January 2009 and August 2011 were retrospectively collected.
      Pearson 2 test and Logistic regression analysis were used to analyze the risk
      factor of perioperative complication. Cox regression analysis was used to
      evaluate the influence of perioperative complications on the prognosis in
      patients after radical gastrectomy. Kaplan-Meier survival curve was applied to
      calculate the survival. RESULTS: Of 1 148 patients, 851 were male, 297 were
      female, age ranged from 19 to 89 (average 59.9) years. Perioperative complication
      occurred in 312 cases (27.2%), including 140 cases of pulmonary infection and 53
      cases of abdominal infection. Multivariate Logistic regression analysis showed
      that >=65 years old (OR:0.736, 95%CI: 0.558 to 0.971, P=0.030), serum albumin
      less than 35 g/L(OR:2.626, 95%CI: 1.479 to 4.665, P=0.001), Borrmann type
      IIII((OR: 0.748, 95%CI: 0.610 to 0.917, P=0.005), tumor site at upper 1/3 of
      stomach (OR:1.326, 95%CI:1.167 to 1.506, P=0.000), combined organ
      resection(OR:0.624, 95%CI:0.428 to 0.909, P=0.014) were independent risk factors
      of perioperative complication. Tumor site at upper 1/3 of stomach (OR:1.649,
      95%CI: 1.368 to 1.988, P=0.000), >=65 years old (OR:0.548, 95%CI:0.379 to 0.792,
      P=0.001), without intraoperative chemotherapy (OR:1.671, 95%CI:1.146 to 2.437,
      P=0.008) were independent risk factors of perioperative pulmonary infection;
      Borrmann type IIII((OR:0.576, 95%CI:0.369 to 0.900, P=0.015), with intraoperative
      chemotherapy (OR:0.431, 95%CI:0.230 to 0.810, P=0.009), intraoperative blood loss
      >=400 ml(OR:0.411, 95%CI:0.176 to 0.959, P=0.040) and combined organ resection
      (OR:0.412, 95%CI:0.215 to 0.789, P=0.008) were independent risk factors of
      perioperative intraperitoneal infection. Cox regression analysis revealed that
      without intraoperative chemotherapy, proximal subtotal or total gastrectomy, TNM
      stage III(, N3 stage lymph node metastasis, positive soft tissue outside lymph
      node, combined organ resection and organ failure were independent risk factors
      affecting the prognosis of gastric cancer patients after radical resection (all
      P<0.05), however the perioperative complication was not independent risk factor
      affecting the prognosis (P=0.259). The median survival time was 35 months, and 5
      year survival rate was around 38.7%. The median survival time of gastric cancer
      patients with operative complications and without complications were 28.0 and
      36.5 months, and the 5-year survival rates were 37.2% and 39.3%, whose difference
      was not statistically significant (P=0.259). CONCLUSION: There is a higher risk
      of perioperative complication in those gastric cancer patients with old age,
      preoperative low serum albumin level, tumor site at upper 1/3 of stomach,
      Borrmann type IIII(, intraoperative combined organ resection, while the
      perioperative complication has no significant effects on the long-term survival.

PMID- 29354901
TI  - [Effects of laparoscopic sleeve gastrectomy on insulin secretion patterns in
      morbidly obese patients].
AB  - OBJECTIVE: To assess the effects of laparoscopic sleeve gastrectomy (LSG) on
      insulin secretion mode and metabolism of glucose and lipid in morbidly obese
      patients. METHODS: Clinical data of 65 morbidly obese patients [body mass index
      (BMI) >=30 kg/m2] undergoing LSG at Shanghai 10th People's Hospital from August
      2012 to December 2016 were retrospectively analyzed. According to the result of
      OGTT, these obese patients were divided into three groups: normal glucose
      tolerance (NGT, 23 cases), impaired glucose tolerance (IGT, 22 cases) and type 2
      diabetes mellitus (DM, 20 cases) groups. Twenty-two healthy people [BMI (23.1+/
      1.4) kg/m2] were used as control group. The anthropometries parameters [weight,
      BMI, waist circumference, body fat percentage, excess weight loss(%EWL)], glucose
      metabolic indices [fasting plasma glucose (FPG), fasting insulin (FINS),
      glycosylated hemoglobin (HbA1c), homeostasis model assessment-insulin resistance
      index (HOMA-IR)], lipid profile (TC, TG, HDL-C, LDL-C) and inflammatory factor
      (UA, TNF-alpha) of 3 groups were detected before operation and at postoperative 1
      , 3-, 6-month. These variables were analyzed among morbidly obese groups before
      and after surgery and compared to control group. Clinical registration number of
      this study was ChiCTROCSl2002381. RESULTS: Body weight, waist circumference and
      BMI of morbidly obese patients all decreased at postoperative 1-, 3-, 6-month.
      Postoperative %EWL increased obviously to (71.5+/-24.7)% with the highest range
      in DM group. Percentage of successful weight loss (%EWL>50%) in NGT, IGT and DM
      groups was 63.6%, 83.9% and 90.0% at postoperative 6-month respectively, and DM
      group was also the highest. At postoperative 6-month, HbA1c of 3 morbidly obese
      groups became normal; FPG and postprandial 2-hour glucose of IGT and DM group
      decreased to normal level; insulin level of 3 morbidly obese groups decreased
      obviously compared to pre-operation (all P<0.05), especially FINS and
      postprandial 2-hour insulin became normal without significant difference of
      control group (P>0.05), while postprandial 30-minute and 60-minute insulin levels
      in 3 groups were still higher as compared to control group. The insulin secretion
      curves of morbidly obese groups showed hyperinsulinemia before surgery. The peak
      of insulin secretion curve in IGT and DM group moved back to postprandial 120
      minute before operation, and returned to 60-minute after operation, with basic
      normal rhythm of secretion curve. Preoperative HOMA-IR in all 3 morbidly obese
      groups was higher than that in control group (all P<0.05) and remarkably lower at
      postoperative 6-month compared to pre-operation(P<0.05). In 3 morbidly obese
      groups after operation, TG decreased, HDL-C increased, UA and TNF-alpha decreased
      significantly compared to before operation (all P<0.05). At postoperative 6
      month, the HOMA-IR of DM group was positively correlated with BMI (r=0.236,
      P=0.004) and TNF-alpha (r=0.228, P=0.033), and was not correlated with HDL
      C(P>0.05). CONCLUSIONS: LSG can effectively ameliorate hyperinsulinemia and
      insulin secretion curve, and improve metabolic disorder and insulin resistance of
      different stage in obesity patients with glucose metabolic disorder. Insulin
      resistance is correlated with body weight and inflammatory factors.

PMID- 29354902
TI  - [Comparison of laparoscopic-assisted anorectoplasty and posterior sagittal
      anorectoplasty for high and intermediate anorectal malformations].
AB  - OBJECTIVE: To compare the efficacy of laparoscopic-assisted anorectoplasty
      (LAARP) and posterior sagittal anorectoplasty (PSARP) for high and intermediate
      anorectal malformation (ARM). METHODS: Clinical data 60 children with high and
      intermediate ARM who underwent LAARP (40 cases of three-port laparoscopy, 20
      cases of transumbilical single incision laparoscopy ) between January 2010 to
      December 2014 were retrospectively analyzed. Clinical data of 36 children with
      high and intermediate ARM who underwent PSARP between January 1992 to December
      2002 were used as control. The duration of operation, blood loss, hospital stay,
      postoperative complications and long-term anal function were compared between two
      groups. Krickenbeck classification was applied to assess the anorectal function.
      RESULTS: Baseline data, such as gender, age at operation, sacral index and
      proctatresia site, were not significantly different between two groups. As
      compared to PSARP group, LAARP group presented shorter operative time [(113+/-13)
      min vs. (132+/-10) min, P=0.01], less operative blood loss [(11.5+/-1.6) ml vs.
      (14.3+/-1.7) ml, P=0.03], shorter postoperative hospital stay [(6.9+/-0.7) d vs.
      (8.2+/-0.8) d, P=0.02] and lower morbidity of postoperative complication [11.7%
      (7/60) vs. 27.8% (10/36), P=0.02]. Postoperative defecation evaluation showed
      that LAPPR group had lower percentage of 2-3 grade constipation than PSARP group
      [0% vs. 22.2%(8/36), P=0.00]. While percentage of 2-3 grade voluntary bowel
      movement [5.9% (3/51) vs. 16.7% (6/36), P=0.20] and percentage of 2-3 grade
      soiling [5.9%(3/51) vs. 16.7%(6/36), P=0.20] were not significantly different
      between two groups. CONCLUSIONS: LAARP is safe and effective in the treatment of
      high and intermediate ARM. Compared with PSARP, LAARP has some advantages, such
      as better cosmetic results and faster recovery.

PMID- 29354903
TI  - [The value of MRI with CUBE sequence in early evaluation of the efficacy of
      neoadjuvant therapy for locally advanced rectal cancer].
AB  - OBJECTIVE: To investigate the value of MRI with CUBE sequence in early evaluation
      of the efficacy of neoadjuvant therapy (NAT) for locally advanced rectal cancer.
      METHODS: Inclusion criteria: (1) rectal cancer proven by biopsy; (2) locally
      advanced rectal cancer (T3-4 or positive lymph nodes) with distance from lower
      edge of tumor to anal verge within 12 cm diagnosed by MRI before NAT; (3)
      acceptance of NAT treatment regulations and completion of NAT; (4) completion of
      routine MRI scan and CUBE scan before and after 2-course NAT chemotherapy
      (including new neoadjuvant chemotherapy and chemoradiotherapy); (5) completion of
      surgery 6-8 weeks after NAT; (6) exclusion of any previous NAT due to rectal
      malignant tumor or other tumors; (7) exclusion of poor image quality of
      preoperative routine MRI insufficient for rectal cancer staging or of CUBE image
      insufficient for tumor volume measurement. Fifty patients with advanced local
      rectal cancer were recruited in our hospital from February 2014 to January 2016.
      All the patients underwent MRI before and after 2-course neoadjuvent therapy.
      Tumor volume on CUBE were measured and the volume changes were calculated: volume
      difference= pre-treatment volume-post-treatment volume, volume change rate= (pre
      treatment volume-post-treatment volume)/ pre-treatment volume. All the patients
      were categorized into sensitive and non-sensitive group according to postsurgical
      pathology. Comparisons were made between both groups before and after therapy.
      ROC curve was used to evaluate the value of CUBE-associated parameters in
      predicting the efficacy of rectal cancer. RESULTS: Among enrolled 50 patients
      with rectal cancer, 31 were male and 19 were female, with mean age of 49.1 years
      (range 21 to 70 years). T-staging by MRI before NAT was T2N1-2 in 1 case, T3 in
      43 cases, T4 in 6 cases. The number of patients after NAT from tumor regression
      grading (TRG) 0 to TRG3 was 14, 13, 18, 5, respectively. The sensitive group and
      insensitive group were 45 cases and 5 cases. Mean tumor volume before and after
      preoperative 2-course NAT was 18.70 (4.14 to 91.77) cm3 and 9.26 (1.02 to 52.58)
      cm3, respectively, whose difference was significant (U=-5.826, P<0.001). Both
      measure values of overall tumor volume before and after preoperative NAT between
      sensitive group and insensitive group did not show significant differences(all
      P>0.05). While sensitivity group had significantly higher volume difference and
      change rate compared to insensitive group [ (11.90+/-10.01) cm3 vs. (0.65+/-3.93)
      cm3, P=0.005; 0.45+/-0.28 vs. 0.09+/-0.36, P=0.010]. ROC curve revealed that the
      optimal cutoff value of accurate identification of patients with NAT sensitive
      was 1.96 cm3 for volume difference with sensitivity 86.7% and specificity 80%,
      and 0.06 for volume change rate with sensitivity 93.3% and specificity 60%.
      CONCLUSION: MRI CUBE can predict the efficacy of NAT for early rectal cancer
      patients accurately and sensitively through the detection of tumor volume change
      before and after NAT.

PMID- 29354904
TI  - [Clinical application of pelvic floor reconstruction in extralevator
      abdominoperineal excision for low rectal cancer].
AB  - OBJECTIVE: To investigate the safety and clinical significance of pelvic floor
      reconstruction in extralevator abdominoperineal excision(ELAPE) for advanced low
      rectal cancer. METHODS: The clinical efficacy was retrospectively analyzed in 30
      patients with low rectal cancer who underwent ELAPE from January 2013 to December
      2016 in Nanjing Drum Tower Hospital, the affiliated Hospital of Nanjing
      University Medical School. There were 21 male patients and 9 female, with an
      average age of 61.7 years old. We used 13*15 cm Biodesign biologic meshes(Cook,
      China) for the reconstruction and the procedure involved soaking in saline
      solution for 5 minutes and fixation of the mesh to the cut edges of the levators
      by non-absorbable 2-0 sutures. A perineal drain was used and was removed when
      drainage was minimal. Potassium permanganate was used for hip bath after removing
      the stitches. The surgical procedure, postoperative complications, prognosis and
      follow-up of all these patients were documented. RESULTS: The operations of all
      patients were completed successfully. ELAPE could remove more para cancer tissues
      in the distant rectum. There was no rectum perforation, and the circumferential
      resection margins of all specimens were proved to be negative. During the follow
      up of 21 months, only 2 patients suffered incision infection and healed
      uneventfully after strengthening the dressing. No one developed perineal
      breakdown, bulge or intestinal obstruction, as well as local recurrence and
      pelvic floor hernia. There was also no complication related to mesh. The average
      hospitalization time was 10 days (9-15 days). CONCLUSIONS: The ELAPE could render
      a low occurrence of intraoperative perforations and circumferential resection
      margins. Reconstruction of pelvic floor with biologic meshmight lower the
      complication incidences associated with the perineal region.

PMID- 29354905
TI  - [Advancement of minimally invasive esophagectomy].
AB  - Esophageal cancer is one of the most common malignant digestive system cancers in
      China, which has high incidence and mortality. Nowadays, surgery remains the most
      important part of the comprehensive treatments. Conventional open esophagectomies
      are highly traumatic with high morbidity, while minimally invasive esophagectomy
      has been increasingly used with the development of surgical instruments and
      techniques in recent years. Compared with conventional open esophagectomy(OE),
      what are the advantages of minimally invasive esophagectomy (MIE) and which is
      preferable? This review briefly introduces the developing history of MIE and
      common procedures. Then we review large amounts of relevant literatures,
      comparing MIE with OE in perioperative rehabilitation, lymph node dissection and
      long-term survival. Results showed that compared with OE, MIE had less blood loss
      during operation, less postoperative pulmonary complications, shorter hospital
      stay and ICU time, meanwhile, there were no significant differences in the
      incidence of anastomotic leak, perioperative mortality, R0 resection and total
      number of resected lymph nodes. However, there are still no clear results of
      comparisons on operative time, recurrent laryngeal nerve palsy, and long-term
      survival, thus, more supportive evidences from prospective large-sample
      observation studies or randomized controlled trials are still needed.
      Furthermore, this review also presents the application and the progress of
      robotic-assisted MIE(RAMIE), demonstrates the current use of robotic technology
      during esophagectomies, meanwhile forecasts the future advancements of RAMIE. For
      the moment, the limitations of RAMIE to be widely used mainly include the cost
      and controlling of surgical indications, and we hope these can be settled in the
      coming years.

PMID- 29354908
TI  - Erratum.

PMID- 29354906
TI  - Baseline and postoperative levels of C-reactive protein and interleukins as
      inflammatory predictors of atrial fibrillation following cardiac surgery: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Postoperative atrial fibrillation (POAF) is a leading arrhythmia with
      high incidence and serious clinical implications after cardiac surgery. Cardiac
      surgery is associated with systemic inflammatory response including increase in
      cytokines and activation of endothelial and leukocyte responses. AIM: This
      systematic review and meta-analysis aimed to determine the strength of evidence
      for evaluating the association of inflammatory markers, such as C-reactive
      protein (CRP) and interleukins (IL), with POAF following isolated coronary artery
      bypass grafting (CABG), isolated valvular surgery, or a combination of these
      procedures. METHODS: We conducted a meta-analysis of studies evaluating measured
      baseline (from one week before surgical procedures) and postoperative levels
      (until one week after surgical procedures) of inflammatory markers in patients
      with POAF. A compre-hensive search was performed in electronic medical databases
      (Medline/PubMed, Web of Science, Embase, Science Direct, and Google Scholar) from
      their inception through May 2017 to identify relevant studies. A comprehensive
      subgroup analysis was performed to explore potential sources of heterogeneity.
      RESULTS: A literature search of all major databases retrieved 1014 studies. After
      screening, 42 studies were analysed including a total of 8398 patients. Pooled
      analysis showed baseline levels of CRP (standard mean difference [SMD] 0.457
      mg/L, p < 0.001), baseline levels of IL-6 (SMD 0.398 pg/mL, p < 0.001),
      postoperative levels of CRP (SMD 0.576 mg/L, p < 0.001), postoperative levels of
      IL-6 (SMD 1.66 pg/mL, p < 0.001), postoperative levels of IL-8 (SMD 0.839 pg/mL,
      p < 0.001), and postoperative levels of IL-10 (SMD 0.590 pg/mL, p < 0.001) to be
      relevant inflammatory parameters significantly associated with POAF. CONCLUSIONS:
      Perioperative inflammation is proposed to be involved in the pathogenesis of
      POAF. Therefore, perioperative assessment of CRP, IL-6, IL-8, and IL-10 can help
      clinicians in terms of predicting and monitoring for POAF.

PMID- 29354909
TI  - [Post-stroke unilateral spatial neglect treated with acupuncture and
      rehabilitation: a randomized controlled trial].
AB  - OBJECTIVE: To observe the impacts on post-stroke unilateral spatial neglect
      treated with acupuncture for "regaining consciousness, benefiting marrow and
      opening orifices" and rehabilitation. METHODS: Forty patients of post-stroke
      unilateral spatial neglect were randomized into an observation group and a
      control group, 20 cases in each one. In the observation group, acupuncture was
      applied to the acupoints for "regaining consciousness, benefiting marrow and
      opening orifices", named Baihui (GV 20), Sishencong (EX-HN 1), Benshen (GB 13),
      Shenting (GV 24), and the bilateral yuan-primary points and luo-connecting points
      of the heart meridian, pericardium meridian and kidney meridian, as well as the
      acupoints along the affected meridians. Additionally, the rehabilitation was
      provided. In the control group, acupuncture at the acupoints along the affected
      meridians and rehabilitation were adopted. The treatment was given once a day, 5
      times a week. After 8 weeks of treatment the evaluation was made. the indexes of
      unilateral spatial neglect such as line bisection test, the score of the mini
      mental state examination (MMSE), the score of simple Fugl-Meyer motor function
      assessment and the modified Barthel indexes were adopted for the assessment of
      the severity of unilateral spatial neglect, cognitive function, motor function,
      and the activities of daily living. RESULTS: After treatment, the indexes of
      unilateral spatial neglect (line bisection test, line cancellation test, clock
      drawing test and copying drawing test), MMSE score, the simple Fugl-Meyer motor
      function assessment and modified Barthel indexes were all improved as compared
      with those before treatment in the two groups (all P<0.01). The improvements in
      the observation group were more obvious than those in the control group (P<0.05,
      P<0.01). CONCLUSION: The combination of acupuncture treatment for "regaining
      consciousness, benefiting marrow and opening orifices" and rehabilitation much
      more effectively alleviates the severity of post-stroke unilateral spatial
      neglect and improves the motor function and the activities of daily living in the
      patients.

PMID- 29354910
TI  - [Individualized scalp acupuncture for motor dysfunction in stroke: a randomized
      controlled trial].
AB  - OBJECTIVE: To evaluate the effect of individualized scalp acupuncture base on
      location of brain function for motor dysfunction in stroke patients. METHODS: A
      total of 180 patients were randomly assigned into an individualized scalp
      acupuncture (ISA) group, a conventional scalp acupuncture (CSA) group and a
      rehabilitation group, 60 cases in each one. In the ISA group, we stimulated
      Sishencong (EX-HN 1), motor area and balance area, matched with pre-motor area
      for higher muscle tension, application area and NIE 's three-needle for
      involuntary motion, application area for poor motor coordination, forehead five
      needle for cognitive disorder, sensory area for sensory disturbance. In the CSA
      group, the affected Dingnieqianxiexian (MS 6), Dingniehouxiexian (MS 7) and
      Zhenxiapangxian (MS 14) were selected. Rehabilitation was used during needle
      retained in the two groups. Simple rehabilitation was used in the rehabilitation
      group. All the treatment was given from Monday to Friday for 4 weeks, once a day
      for 20 times. Eight-week follow-up was applied. The Fugl-Meyer assessment (FMA)
      for motor function, modified Barthel Index (MBI) were used to evaluate clinical
      effect. RESULTS: After treatment and at follow-up, FMA and MBI scores increased
      compared with those before treatment in the three groups(all P<0.01), with
      significant differences among the three groups (all P<0.000 1) and better results
      in the ISA group compared with those in the other two groups (P<0.05, P<0.01) at
      the two time points. The FMA and MBI scores in the CSA group were higher than
      those in the rehabilitation group after treatment and at follow-up (all P<0.05).
      CONCLUSION: The individualized scalp acupuncture can improve motor dysfunction
      and self-care ability of daily life for stroke patients.

PMID- 29354911
TI  - [Clinical efficacy of electroacupuncture combined with motor imagery therapy on
      hemiplegic cerebral infarction].
AB  - OBJECTIVE: To explore the effects of electroacupuncture (EA) combined with motor
      imagery therapy on motor function and activity of daily living in patients with
      hemiplegic cerebral infarction. METHODS: Ninety patients with hemiplegic cerebral
      infarction were randomly divided into a rehabilitation group, an EA group and a
      comprehensive group, 30 patients in each one. The patients in the rehabilitation
      group were treated with regular care, medication and rehabilitation training;
      based on the rehabilitation group, the patients in the EA group were treated
      mainly with electroacupuncture at Baihui (GV 20), Dingnieqianxiexian (MS 6),
      Dingniehouxiexian (MS 7), Jianyu (LI 15), Waiguan (TE 5), Fengshi (GB 31) and
      Sanyinjiao (SP 6); with the arrival of qi. EA device was connected for 30 min.
      The patients in the comprehensive group were treated with EA as the EA group and
      motor imagery therapy, 20 min per treatment. The treatment was given once a day,
      five treatments per week, and totally 4-week treatment was performed. The Barthel
      index and Brunnstrom score before and after treatment were observed in the three
      groups. RESULTS: Three cases did not finish the trial and finally 87 cases were
      included into analysis, including 30 cases in the rehabilitation group, 29 cases
      in the EA group and 28 cases in the comprehensive group. Compared before
      treatment, the Barthel index and Brunnstrom score were significantly improved
      after treatment in the three groups (all P<0.01); after treatment, the Barthel
      index in the EA group and comprehensive group was significantly higher than that
      in the rehabilitation group (both P<0.01); the lower extremity score of
      Brunnstrom score in the comprehensive group was better than those in the EA group
      and rehabilitation group (both P<0.05). CONCLUSION: EA combined with motor
      imagery therapy and rehabilitation can significantly improve the motor function
      and activity of daily living in patients with hemiplegic cerebral infarction,
      which is superior to rehabilitation alone or EA alone.

PMID- 29354912
TI  - [Clinical observation of acupuncture plus electroacupuncture for hand spasm in
      stroke patients].
AB  - OBJECTIVE: To observe the effect difference between acupuncture combined with
      electroacupuncture (EA) and simple acupuncture for hand spasm in stroke patients.
      METHODS: Sixty patients were randomly assigned into an acupuncture group and a
      combination group, 30 cases in each one. Patients in the two groups were treated
      with acupuncture at the affected Jianyu (LI 15), Binao (LI 14), Jianliao (TE 14),
      Quchi (LI 11), Shousanli (LI 10), Waiguan (TE 5), Futu (ST 32), Liangqiu (ST 34),
      Xuehai (SP 10), Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Yinlingquan
      (SP 9), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR 3), and the points at the
      middle of all the dorsal muscles between metacarpal bones. EA with discontinuous
      wave was used in the combination group at Waiguan (TE 5) and the middle point of
      the dorsal muscle between the second and the third metacarpal bones. The
      treatment was given for 40 min, once a day for 3 courses, five treatment per
      week, 4 weeks as a course. The modified Ashworth scale (MAS), the Fugl-Meyer
      finger motor function rating scale and the modified Barthel index (BI) were
      observed before and after treatment in the two group. RESULTS: The MAS scores
      after treatment significantly decreased compared with those before treatment in
      the two groups (both P<0.05), with lower score in the combination group (P<0.05).
      The Fugl-Meyer scores and BI scores after treatment increased in the two groups
      (all P<0.05), with higher scores in the combination group (both P<0.05).
      CONCLUSION: EA combined with acupuncture can more apparently alleviate hand
      spasm, promote the recovery of hand function, improve the quality of life for
      stroke patients than simple acupuncture.

PMID- 29354913
TI  - [Effects of auricular plaster therapy on quality of life in uremia patients after
      parathyroidectomy plus autograft].
AB  - OBJECTIVE: To observe the effects of auricular plaster therapy on quality of life
      in uremia patients after parathyroidectomy plus autograft (PTX+AT). METHODS: A
      total of 34 uremia patients complicated with secondary hyperparathyroidism (SHPT)
      who received PTX+AT were randomly divided into an observation group and a control
      group, 17 cases in each one. The patients in the control group were treated with
      calcium supplementation after surgery, 1 to 2 mg/kg an hour; one day after
      surgery, the patients were treated with oral administration of calcium carbonate
      before meals, 1.5 g, three times per day, and calcitriol (0.5 to 4 MUg/d) was
      added if necessary. None-heparin hemodialysis was performed for one week after
      surgery. Besides calcium supplementation, patients in the observation group were
      treated with auricular plaster therapy at Shenmen (TF4), Jiaogan (AH6a), Neifenmi
      (CO18) and Shen (CO10). The laboratory indexes, including immunoreactive
      parathyroid hormone (iPTH), calcium, phosphorus, and SF-36 questionnaire,
      including 8 dimensions of physical function (PF), role-physical (RP), bodily pain
      (BP), general health (GH), vitality (VT), social function (SF), role-emotional
      (RE) and emotional well-being (EB), were observed before surgery and 1 week, 2
      weeks, 4 weeks and 8 weeks after surgery in the two groups. RESULTS: The iPTH in
      the two groups was significantly decreased 1 week, 2 weeks, 4 weeks and 8 weeks
      after surgery, and the serum calcium and phosphorus were also improved to a
      certain degree (all P<0.05); however, the differences of iPTH, calcium and
      phosphorus between the two groups were not significant at each time point after
      surgery (all P>0.05).The PF, RP, BP, GH, VT, SF, RE and EB of SF-36 in the two
      groups before surgery were lower than the normal score; after surgery, each
      dimension of SF-36 were improved to some extent in the two groups (all P<0.05).
      Eight weeks after surgery, the improvement of PF, RP, BP, GH and EB in the
      observation group was superior to that in the control group (all P<0.05);
      however, in terms of VT, SF and RE, no significant difference was observed
      between the two groups (all P>0.05). CONCLUSION: The auricular plaster therapy
      can improve the physical and mental health, relieve pain and improve quality of
      life in patients with uremia after PTX+AT, which is superior to calcium carbonate
      alone.

PMID- 29354914
TI  - [Effect difference between acupuncture and moxibustion for functional dyspepsia:
      a randomized controlled trial].
AB  - OBJECTIVE: To investigate the effect difference between acupuncture and
      moxibustion for functional dyspepsia (FD). METHODS: Sixty patients with FD were
      randomized into an acupuncture group (29 cases with 1 rejecting) and a
      moxibustion group (27 cases with 3 dropping). The corresponding manipulations for
      4 courses were applied at Zhongwan (CV 12) and Zusanli (ST 36) in the two groups,
      continuous 5 times as 1 course with 2 days between two courses, once a day and
      total 20 times. Leed's dyspepsia questionnaire (LDQ) and Nepean dyspepsia index
      (NDI) were tested before and after treatment, and safety was evaluated. RESULTS:
      After treatment, the total LDQ scores decreased in the two groups (both P<0.01),
      with statistical different value between the two groups (P<0.05). Upper abdominal
      pain, early satiety, epigastric burning in the acupuncture group were improved
      more obviously compared with those in the moxibustion group (all P<0.01). The NDI
      scores in the two groups increased after treatment (both P<0.01), without
      statistical different value before and after treatment (P>0.05). CONCLUSION:
      Acupuncture and moxibustion are effective for FD and acupuncture shows
      superiority.

PMID- 29354915
TI  - [Clinical study of the combination of acupoint catgut-embedding therapy and
      auricular point pressure in the treatment of insomnia of spleen and stomach
      disharmony pattern].
AB  - OBJECTIVE: To observe the differences in the clinical therapeutic effects on
      insomnia of spleen and stomach disharmony pattern in comparison of the
      combination of acupoint catgut-embedding therapy and auricular point pressure
      with the simple application of auricular point pressure. METHODS: One hundred and
      eighty patients of insomnia of spleen and stomach disharmony pattern were
      randomized into an observation group (93 cases) and a control group (87 cases).
      In the observation group, the combination of acupoint catgut-embedding therapy
      and auricular point pressure was adopted. The acupoint catgut-embedding therapy
      was applied at Zhongwan (CV 12), Anmian (Extra), Xinshu (BL 15), Pishu (BL 20),
      Weishu (BL 21), Zusanli (ST 36), Yinlingquan (SP 9) and Sanyinjiao (SP 6), once
      every two weeks. The auricular point pressure was applied to Shenmen (TF4),
      Pizhixia (AT4), Xin (CO15), Pi (CO13), Wei (CO4) on both sides alternatively,
      twice a week. The duration of treatment was 2 months for the two groups. In the
      control group, the auricular point pressure was simply used with the same points,
      manipulation and treatment duration as the observation group. After treatment,
      the clinical therapeutic effects were observed in the patients of the two groups.
      The Pittsburgh sleep quality index (PSQI) score was compared before and after
      treatment in the two groups. The recurrence was followed up in 3 months after the
      end of treatment. RESULTS: It was observed that 2 cases were dropped out in the
      observation group, 4 cases in the control group. The dropped out cases were
      considered to be ineffective. After treatment, the total effective rate was 92.5%
      (86/93) in the observation group and was 80.5% (70/87) in the control group. The
      result in the observation group was better than that in the control group
      (P<0.05). After treatment, PSQI scores were all reduced apparently in the two
      groups as compared with those before treatment (both P<0.05). The score after
      treatment and the different value before and after treatment in the observation
      group were lower than those in the control group (both P<0.05). In 3-month follow
      up after treatment, the recurrence rate was 3.2% (3/93) in the observation group,
      which was lower than 13.8% (12/87) in the control group (P<0.05). CONCLUSION: In
      the treatment of insomnia of spleen and stomach disharmony pattern, the acupoint
      catgut-embedding therapy combined with auricular point pressure are superior to
      the simple application of auricular point pressure in the clinical therapeutic
      effects, improving sleep quality and reducing the recurrence rate.

PMID- 29354916
TI  - [Clinical observation of fast acupuncture for cervical type of cervical
      spondylosis].
AB  - OBJECTIVE: To compare the effects between fast acupuncture and retaining
      acupuncture for the cervical type of cervical spondylosis. METHODS: Sixty
      patients were randomized into a fast acupuncture group and a retaining needle
      group, 30 cases in each one. The acupoints in the two groups were Fengchi (GB
      20), Jiaji (EX-B 2, C2, C4, C6) and Jianjing (GB 21), Jianjing 1 (Extra) and
      Jianjing 2 (Extra). The needles in the fast acupuncture group were out after qi
      arrival, while those in the retaining needle group were retained for 30 min,
      three times a week, once the other day. One week was seen as a course and the
      treatment was given for 2 courses. The indices were observed before and after
      treatment, including Northwick Park neck pain questionnaire (NPQ), short-form
      McGill pain questionnaire (SF-MPQ) [pain rating index (PRI), visual analogue
      scale (VAS) and present pain intensity (PPI)]. The effects were compared in the
      two groups. RESULTS: After treatment, the NPQ score was lower than that before
      treatment in the two groups (both P<0.01), and that in the fast acupuncture group
      was better (P<0.01). All the items of SF-MPQ decreased compared with those before
      treatment in the two groups (all P<0.01), with the better results of PRI
      sensation score and PRI total score in the fast acupuncture group (both P<0.05).
      The PRI feeling score, VAS score, and PPI score were not significantly different
      after treatment between the two groups (all P>0.05). The total effective rate in
      the fast acupuncture group was 83.3% (25/30), not significantly different from
      76.7% (23/30) in the retaining needle group (P>0.05). CONCLUSION: Fast
      acupuncture and retaining needle are both effective for the cervical type of
      cervical spondylosis, which can apparently improve the clinical symptoms. Fast
      acupuncture is superior to retaining acupuncture.

PMID- 29354917
TI  - [Clinical research for rehabilitation training combined with modified shu
      acupuncture for joint dysfunction after meniscal suture surgery].
AB  - OBJECTIVE: To compare the effects on joint dysfunction after meniscal suture
      surgery between rehabilitation training combined with modified shu-acupuncture
      and simple rehabilitation training. METHODS: Seventy-one patients with meniscal
      suture surgery were randomized into an observation group (n=36) and a control
      group (n=35). Patients in the observation group received modified shu-acupuncture
      combined with rehabilitation training. Acupuncture for 8 weeks were at Zutonggu
      (BL 65), Shugu (BL 66), Neiting (ST 44), Xiangu (ST 43), Xiaxi (GB 43), Zulinqi
      (GB 41), Dadu (SP 2), Taibai (SP 3), Xingjian (LR 2), and Taichong (LR 3), once a
      day for continuous 6 days with 1 day for rest. Patients in the control group
      received simple rehabilitation training for continuous 8 weeks. The training
      included quadriceps femoris, range of knee joint motion and motion and limb
      walking on the affected side. The effect score for meniscus injury after
      treatment from Japanese Orthopaedics Association (JOA) and visual analogue scale
      (VAS) score were recorded before and after treatment. The effects were compared
      in the two groups. RESULTS: After treatment, the VAS and JOA scores were improved
      in the two groups (all P<0.05), with better results in the observation group
      (both P<0.05). The effective rate was 91.7% (33/36) in the observation group,
      which was better than 80.0% (28/35) in the control group (P<0.05). CONCLUSION:
      Rehabilitation training combined with shu-acupuncture achieve better effect than
      simple rehabilitation training for joint dysfunction after meniscal suture
      surgery.

PMID- 29354918
TI  - [Distribution of algesia sensitized acupoints in the patients of intestinal
      cancer].
AB  - OBJECTIVE: To judge whether algesia sensitization of some acupoints is existed
      and whether the acupoint algesia sensitization area is expanded in the patients
      of intestinal cancer. METHODS: Totally, 30 patients of intestinal cancer and 30
      healthy subjects were included. The electronic Von Fray was used to determine the
      pressure-pain thresholds at 13 acupoints relevant with gastrointestinal disorders
      and the reference points at the sites 1 cun and 2 cun lateral to those points as
      well as the sites at the corresponding nerve segments. Compared with the pressure
      pain thresholds at the reference points of the different segments, the relative
      value was calculated. The changes were analyzed in the pressure-pain thresholds
      at the relevant acupoints on the body surface in the patients of intestinal
      cancer as compared with the relative pressure-pain thresholds in the healthy
      volunteers. RESULTS: The pressure-pain thresholds at Zusanli (ST 36), Shangjuxu
      (ST 37), Xiajuxu (ST 39), Quchi (LI 11) and Dachangshu (BL 25) in the patients of
      intestinal cancer were all significantly reduced as compared with those of the
      healthy subjects (P<0.05, P<0.01, P<0.001). At the non-acupoint sites 1 cun and 2
      cun lateral to those acupoints as well as at the sites of the same segments, the
      pressure-pain thresholds were reduced significantly as compared with the control
      group (P<0.05, P<0.01, P<0.001). Particularly, the sensitization zone of
      Yinlingquan (SP 9) focused on the acupoint, the site 1 cun lateral to it as well
      as the non-acupoint sites of the same segments (P<0.01, P<0.001). CONCLUSION: The
      acupoint sensitization is displayed at Zusanli (ST 36), Shangjuxu (ST 37),
      Xiajuxu (ST 39), Quchi (LI 11), Dachangshu (BL 25) and Yinlingquan (SP 9) and the
      sensitization area is expended in the patients of intestinal cancer.

PMID- 29354919
TI  - [Effects of electroacupuncture at "Weizhong" (BL 40) on morphology and expression
      of CK and IL-17 in rats with bupivacaine-induced multifidus muscle injury].
AB  - OBJECTIVE: To observe effects of electroacupuncture (EA) at "Weizhong" (BL 40) on
      morphology and expression of creatine kinase (CK) and interleukin-17 (IL-17) in
      rats with bupivacaine-induced multifidus muscle injury. METHODS: A total of 32
      male SD rats were randomly divided into a control group, a model group, a
      Weizhong group and a Shenshu group, 8 rats in each one. The rats in the model
      group, Weizhong group and Shenshu group were treated with intramuscular injection
      of 0.5% bupivacaine to establish the model of multifidus muscle injury; the rats
      in the control group were injected with 0.9% sodium chloride solution. The rats
      in the Weizhong group and Shenshu group were treated with EA (2 Hz/10 Hz in
      frequency, 1~2 mA in intensity) at "Weizhong" (BL 40) and "Shenshu" (BL 23), 20
      min per treatment. No treatment was given in the control group and model group.
      After 14-day treatment of EA, the inflammatory cell count, scar tissues area and
      muscle fiber cross sectional area of multifidus muscle were observed with HE and
      Masson staining method. The activity of CK and serum content of IL-17 were test
      with enzyme-linked immunosorbent assay (ELISA) method; the expression of IL-17 in
      multifidus muscle was measured with immunohistochcmical method. RESULTS: After
      intervention, the inflammatory cell count and scar tissues area in the model
      group, Weizhong group and Shenshu group were higher than those in the control
      group (all P<0.01), but the muscle fiber cross sectional area was significantly
      reduced (all P<0.01); the inflammatory cell count and scar tissues area in the
      Weizhong group and Shenshu group were lower than those in the model group (all
      P<0.01), and the muscle fiber cross sectional area was significantly increased
      (P<0.01, P<0.05). After intervention, the expression of IL-17 in multifidus
      muscle, serum content of IL-7 and activity of CK in the model group, Weizhong
      group and Shenshu group were higher than those in the control group (all P<0.01);
      the expression of IL-17 in multifidus muscle, serum content of IL-7 and activity
      of CK in the Weizhong group and Shenshu group were lower than those in the model
      group (P<0.01, P<0.05); compared with the Shenshu group, the down-regulation of
      IL-17 was more obvisous in the Weizhong group (P<0.01). CONCLUSION: EA at
      "Weizhong" (BL 40) can down-regulate the overexpression of serum CK and IL-17,
      alleviate inflammation reaction and improve the repair of multifidus muscle.

PMID- 29354920
TI  - [Effect of heat-reinforcing needling on serum metabolite profiles in rheumatoid
      arthritis rabbits with cold syndrome].
AB  - OBJECTIVE: To explore heat-reinforcing needling for the metabolite profiling
      changes in serum of rheumatoid arthritis (RA) rabbits with liquid chromatograph
      mass spectrometer (LC-MS) technique, and to investigate its mechanisms. METHODS:
      Forty clean purple blue rabbits were randomized into a normal group, a model
      group, a reinforcing-reducing needling (RRN) group, a twirling-reinforcing
      needling (TRN) group, and a heat-reinforcing needling (HRN) group, 8 cases in
      each group. RA rabbits with cold syndrome were made with ovalbumin and freezing
      except those in the normal group. No treatment was given in the normal and model
      groups. The corresponding manipulations for 7 days were applied at "Zusanli" (ST
      36) in the three acupuncture groups, 30 min a time, once a day. After
      intervention the pain threshold and the local skin temperature of each group were
      observed. Fresh serum from heart was collected for metabonomics detection.
      Principal component analysis (PCA) and partial least squares-discriminant
      analysis (PLS-DA) were adopted. Several metabolites were screened by the variable
      importance in the projection values (VIP>1) and P value (P<0.05). RESULTS: The
      pain threshold and the local skin temperature in the model group were lower than
      those in the normal group (both P<0.05). The pain threshold and the local skin
      temperature in the three acupuncture groups were higher than those in the model
      group after intervention (all P<0.05), which were better in the HRN group than
      those in the RRN and TRN groups (all P<0.05). The serum metabolites of carnitine,
      LysoPC (14?0), LysoPC (18?3), LysoPE (0?0/20?5), LysoPE (0?0/22?1), decylic acid,
      stearic acid and lactic acid in the model group increased compared with those in
      the normal group, and other metabolites decreased, including leucine, valine,
      glutamine, pyroglutamic acid, alpha-ketoglutaric acid, succinic acid, fumaric
      acid, malic acid, galactose, mannose. Those metabolites were correlated fatty
      acid, amino acid, citric acid cycle, and glucose metabolism. The metabolites
      above-mentioned in the three acupuncture groups were regulated in various degrees
      (all P<0.05). Lactic acid decreased and succinic acid, fumaric acid, malic acid,
      galactose, mannose increased more obviously in the HRN group than those in the
      RRN and TRN groups. CONCLUSION: The specificity of heat-reinforcing needling for
      RA presents the regulation for citric acid cycle and glucose metabolism.

PMID- 29354922
TI  - [Explanation on Evidence-based Guidelines of Clinical Practice with Acupuncture
      and Moxibustion: Periarthritis of Shoulder].
AB  - The Evidence-based Guidelines of Clinical Practice with Acupuncture and
      Moxibustion: Periarthritis of Shoulder (Guidelines for short) was officially
      published as a standard of China Association of Acupuncture and Moxibustion in
      2015. From the purpose, methodology, scope, indication, recommended protocol,
      etc., this was explained to provide convenience for clinical use of
      acupuncturists. This Guidelines was developed based on Guidelines comprehensive
      search of literature regarding acupuncture for periarthritis of shoulder, the
      adoption of best evidence, expert experience, patient value across the world,
      methods of evidence quality and GRADE, references of clinical experience of
      famous acupuncturists in the ancient and modern time and expert consensus in the
      national level, which was hoped to provide solid evidence of acupuncture clinical
      treatment for periarthritis of shoulder to ensure the safety and effectiveness.
      In this Guidelines, the stage-by-stage treatment principle of acupuncture for
      periarthritis of shoulder was recommended. In the acute stage, the treatment aim
      was to relieve the pain, and distal acupoints along the meridians were selected
      with strong stimulation; the local acupoints were combined. In the chronic stage
      and rehabilitation stage, the treatment aim was to improve the dysfunction of
      shoulder joint, and acupuncture treatment was based on syndrome differentiation
      of etiology and meridian; the local acupoints were mainly selected, combined with
      acupoints based on etiology and acupoints along meridians.

PMID- 29354921
TI  - [Clinical therapeutic effects of scraping therapy on allergic rhinitis of
      different syndromes].
AB  - OBJECTIVE: To compare the differences in the therapeutic effects on allergic
      rhinitis between scraping therapy and cetirizine and observe the differences in
      the clinical therapeutic effects of scraping therapy on the disease of different
      differentiated patterns/syndromes. METHODS: The included participants of allergic
      rhinitis were randomized into a western medication group and three scraping
      therapy groups, named a lung qi deficiency and cold group, a spleen qi deficiency
      group and a kidney yang deficiency group, 20 cases in each one. In the western
      medication group, cetirizine was prescribed for oral administration, 10 mg, once
      a day, totally for 4 weeks. In the scraping therapy groups, the scraping therapy
      was applied to the running courses of the large intestine meridian of hand
      yangming, the governor vessel and the bladder meridian of foot-taiyang, focusing
      on Yingxiang (LI 20), Yintang (GV29), Hegu (LI 4) and Fengmen (BL 12). In the
      lung qi deficiency and cold group, the scraping focused on the lung meridian of
      hand-taiyin, Feishu (BL 13), Taiyuan (LU 9), Fengchi (GB 20) and Lieque (LU 7).
      In the spleen qi deficiency group, the scraping focused on the spleen meridian of
      foot-taiyin, Pishu (BL 20) and Zusanli (ST 36). In the kidney yang deficiency,
      the scraping focused on the kidney meridian of foot-shaoyin, Mingmen (GV 4) and
      Shenshu (BL 23). The scraping therapy was given once a week, 4 treatments as one
      session and 1 session required (4 weeks). Separately before treatment, after
      treatment and in 3-month follow-up visit, the total score of the main symptoms of
      allergic rhinitis (sneezing, runny nose, nasal obstruction and nasal itch) was
      observed and the clinical therapeutic effects were evaluated. RESULTS: The total
      symptom scores in the patients of the 4 groups after treatment were all reduced
      as compared with those before treatment (all P<0.05). After treatment and in the
      follow-up visit, the total symptom scores of the 3 scraping therapy groups were
      lower than those in the western medication group (all P<0.05), and the score in
      the lung qi deficiency and cold group was lower than those in the spleen qi
      deficiency group and the kidney yang deficiency group (all P<0.05). After
      treatment and in the follow-up visit, the therapeutic effects in the 3 scraping
      therapy groups were better than those in the western medication group (all
      P<0.05). CONCLUSION: The scraping therapy on the basis of the meridians and
      acupoints selection achieves the definite therapeutic effects on allergic
      rhinitis of different differentiated patterns/syndromes, which is better than
      cetirizine. This therapy achieves the much significant short-term and long-term
      therapeutic effects on allergic rhinitis differentiated as lung qi deficiency and
      cold.

PMID- 29354923
TI  - [New opinion on the mechanism of Dazhu (BL 11) for gonalgia with flexion
      extension dysfunction].
AB  - The effect of Dazhu (BL 11) for gonalgia with flexion-extension dysfunction is
      remarkable, and its mechanism of action is interpreted as the influential point
      of bone treating bone diseases. However, through the exploration of a variety of
      literature, the relevant classical research, the views of senior experts, and
      combined with the author's experience, we put forward some new ideas and views
      for reference. Through in-depth analysis about pathogenesis of gonalgia with
      flexion-extension dysfunction and the functional attributes of Dazhu (BL 11),
      combining meridian tendons differentiation and myofascial meridians, we consider
      that Dazhu (BL 11), with its unique "location" advantage, plays the role of
      regulating multiple viscera, meridians, meridian tendons and myofascial
      meridians, which is the mechanism for gonalgia with flexion-extension
      dysfunction.

PMID- 29354924
TI  - [Discussion on the clinical treatment of infantile cerebral palsy with the
      differentiated intervention of meridian points on the spine and back].
AB  - In view of the literature study and clinical practice, the rules of the
      distribution, the general function and the indication of the meridians points on
      the spine and back were explored. The TCM mechanism on the rehabilitation of
      infantile cerebral palsy was studied. The rules of acupoint combination on the
      spine and back were summarized with meridians, main points and supplementary
      points involved in the TCM rehabilitation of infantile cerebral palsy. In view of
      the theoretic study, the advantages on the early infantile motor function, such
      as body turning, sitting, standing and walking, were analyzed with the long-term
      intervention of meridian points on the spine and back. It is showed in the
      rehabilitation of infantile cerebral palsy that the intervention of meridian
      points on the spine and back improves the motor function on the back and relieves
      the incoordination in the development between each system and enhances the
      rehabilitation mechanism of the integration of Chinese and western medicine for
      the functional development of core stability, which provides much more effective
      and more precise approach to the diagnosis and treatment of infantile cerebral
      palsy in clinical practice.

PMID- 29354925
TI  - [Characteristics of acupuncture textbooks on editing mode and content in the
      Republic of China].
AB  - Sixty-seven textbooks in the Republic of China have been collected and divided
      into three stages according to their editing modes, named the early stage (1912
      1927), the middle stage (1928-1939) and the late stage (1940-1949). The
      traditional teaching material of acupuncture was predominated at the early stage
      in the textbook compilation; meanwhile the editing mode was simple, and the
      content of it focuses on meridians, collaterals and acupoints and the modern
      scientific theories have been preliminarily introduced. The textbooks at the
      middle stage were edited as two modes, "western medicine+acupuncture" and
      "general introduction->meridian points->manipulation (techniques of acupuncture
      and moxibustion)->treatment". The knowledge in anatomy, physiology and pathology
      of western medicine has been involved in content, giving the great consideration
      to the clinical practicability. However, a part of textbooks still followed the
      traditional theory of acupuncture at the middle stage. At the late stage, the
      textbooks were edited align with "acupuncture science, moxibustion science,
      meridian point science and treatment science"; or in supplementation of the
      "diagnosis" on the base of "general introduction-> meridian points->techniques of
      acupuncture->treatment", or edited as "general introduction->points->treatment".
      The compilation of the textbooks at this stage not only followed but also
      improved the integration of western and Chinese medicine as that at the middle
      stage, which turned to be more scientific. Additionally, in the teaching content,
      the acupoint was much more considerable as compared with pulse and the section of
      diagnosis has been involved. As a result, a framework of acupuncture discipline
      has been established preliminarily by taking acupuncture technique, moxibustion
      technique, acupoints and treatment as the core. The development of the editing
      mode and content of textbooks played a great impact on the unified compilation of
      the acupuncture textbooks after the foundation of China.

PMID- 29354927
TI  - [Startup mechanism of moxibustion warming and dredging function].
AB  - With "moxibustion" and "warm stimulation" as the keywords, the literature on
      moxibustion mechanism of warming and dredging from June 1st, 1995 to June 1st,
      2016 was collected from PubMed, China National Knowledge Infrastructure (CNKI)
      and Wanfang database. The startup mechanism of moxibustion warming and dredging
      function was analyzed in terms of moxibustion warming stimulation. The results
      were found that moxibustion was based on local rising temperature of acupoint. It
      activated local specific receptors, heat sensitive immune cells, heat shock
      proteins and so on to start the warming and dredging function and produce various
      local effects. The warming stimulation signals as well as subsequent effects
      through nerve and body fluid pathways induced the effects of further specific
      target organs and body systems.

PMID- 29354926
TI  - [Effects of needling depth on clinical efficacy of lumbar disc herniation: a
      systematic review].
AB  - OBJECTIVE: To evaluate the effects of needling depth on clinical efficacy of
      lumbar disc herniation (LDH). METHODS: Ten electronic databases, including China
      National Knowledge Infrastructure (CNKI), VIP Database, Chinese Biomedical
      Literature Database (CBM), Wanfang Database, MEDLINE, CENTRAL, CINAHL PLUS, AMED,
      Embase, PsycINFO, and 6 registry platforms of clinical trials were searched. All
      randomized controlled trials (RCTs) that compared the effect of needling depth on
      clinical efficacy of LDH were collected; in addition, the reference lists of the
      studies included were hand searched. Data were extracted independently by two
      reviewers. RevMan 5.3 was applied to carry out statistical analysis. RESULTS:
      Totally 8 716 articles were retrieved, and 10 RCTs were included after screening,
      involving 1 116 patients. The results showed the effects of deep acupuncture
      onrelievingpain, reducing the Oswestry disability index (ODI), improving total
      effective rate and Japanese Orthopaedic Association (JOA) were superior to those
      of shallow acupuncture in patients with LDH. CONCLUSION: It is preliminarily
      indicated that deep acupuncture is helpful to improve the therapeutic effect of
      LDH; however, due to the low research quality and small sample size, the evidence
      is insufficient, and more high-quality researches are needed to further confirm
      the results.

PMID- 29354928
TI  - [Moxibustion combined with highly active antiretroviral therapy for CD4+ and
      gamma chain cytokines of HIV infected patients].
AB  - OBJECTIVE: To compare the effects of moxibustion combined with highly active
      antiretroviral therapy (HAART) and simple HAART for human immunodeficiency virus
      (HIV) infected patients. METHODS: A total of 100 patients with HIV receiving
      HAART were randomized into an observation group and a control group, 50 cases in
      each one. In the observation group, moxibustion was used at Zusanli (ST 36),
      Guanyuan (CV 4) and Sanyinjiao (SP 6), etc. combined with HAART of zidovudine,
      lamivudine, nevirapine and efavirenzone, etc. Simple HAART was used in the
      control group. The patients were observed for 18 months. The indexes were CD4+,
      CD4+/CD8+, interleukin 2 (IL-2), interleukin 7 (IL-7), the incidence of side
      effects and the score of quality of life. RESULTS: After treatment, CD4+,
      CD4+/CD8+, serum IL-2 and the scores of quality of life (physiological,
      psychological, social relation fields and comprehensive score) increased and
      serum IL-7 decreased compared with those before treatment in the two groups
      (P<0.01, P<0.05), with better results except CD4+ in the observation group
      (P<0.01, P<0.05). The incidences of gastrointestinal side effects and total side
      effects in the observation group were lower than those in the control group (14%
      (7/50) vs 32% (16/50), 58% (29/50) vs 80% (40/50), both P<0.05). CONCLUSION:
      Moxibustion combined with HAART for HIV infected patients could reduce the
      incidence of side effects, improve medication compliance, CD4+/CD8+, IL-2, IL-7
      and the quality of life.

PMID- 29354929
TI  - [Comparison between "five needles therapy" and conventional acupuncture for
      individual symptoms and signs of asthma of latent cold phlegm-fluid in the lung].
AB  - OBJECTIVE: To observe the effect difference between acupuncture of "five needles
      therapy" and conventional acupuncture for asthma of latent cold phlegm-fluid in
      the lung. METHODS: Two hundred and ten cases were randomly assigned into an
      observation group and a control group, 105 cases in each one. Finally 7 cases
      were dropped out in the observation group; 6 cases in the control group. Feishu
      (BL 13), Dazhui (GV 14), Fengmen (BL 12) were used in the observation group;
      conventional acupuncture was used in the control group, and the main acupoints
      were Feishu (BL 13), Zhongfu (LU 1), Tiantu (CV 22), Danzhong (CV 17), Kongzui
      (LU 6), Dingchuan (EX-B 1), Fenglong (ST 40), Fengmen (BL 12), Taiyuan (LU 9).
      The needles were retained for 30 min each time, once a day for continuous 12
      days. The scores of the individual symptoms and signs were observed before
      treatment and on the 3rd, 6th, 9th, 12th days, including pant, cough, cough up
      phlegm, fullness and oppression in the chest and diaphragm, wheezing rale and
      shortness of breath. The clinical effects were compared between the two groups.
      RESULTS: The scores of six individual symptoms and signs on the 3rd, 6th, 9th,
      and 12th days in the two groups were lower than those before treatment (all
      P<0.05), except the score of wheezing rale in the control group on the 3rd day
      (P>0.05). The scores of pant, wheezing rale, cough on the 3rd, 6th, 9th, and 12th
      days in the observation group were lower than those in the control group (all
      P<0.05), except the score of wheezing rale score on the 3rd day (P>0.05). There
      were no significant difference between the two groups about the scores of cough
      up phlegm, fullness and oppression in the chest and diaphragm and shortness of
      breath on the 3rd, 6th, 9th, and 12th days (all P>0.05), except the score of
      fullness and oppression in the chest and diaphragm in the observation group was
      lower than that in the control group on the 12th day (P<0.05). 46 cases were
      clinical cured, 39 cases were markedly effective, 10 cases were effective and 3
      cases were ineffective in the observation group with the total effective rate of
      96.9%. 23 cases were clinical cured, 43 cases were markedly effective, 24 cases
      were effective and 9 cases were ineffective in the control group with the total
      effective rate of 90.9%. The difference was statistical (P<0.05). CONCLUSION:
      "Five needles therapy" has significant therapeutic effect for asthma of latent
      cold phlegm-fluid in the lung, which is better than conventional acupuncture.

PMID- 29354930
TI  - [Skin needle embedding for obese impaired glucose tolerance].
AB  - OBJECTIVE: To explore the effect difference between the skin needle embedding
      therapy and western medication for obese impaired glucose tolerance (IGT).
      METHODS: A total of 300 cases of obese IGT were assigned into an embedding group
      and a western medication group by random number table, 150 cases in each one.
      Standardized diagnosis and treatment programs were applied to reduce blood
      pressure, lipid, weight, and exercise and scientific diet management were used.
      0.25 g oral deltamine was prescribed three times a day in the western medication
      group. Thumb-tack needle for subcutaneous embedding was at bilateral Weiwanxiashu
      (EX-B 3), Ganshu (BL 18), Pishu (BL 20), Tianshu (ST 25) and Zusanli (ST 36) for
      36 to 48 hours on Monday and Thursday, 3 months as a session, with other
      acupoints differentiated. All the treatment was given for 2 years. The indexes
      included the blood sugar indexes [fasting plasma glucose (FPG), 2 h postprandial
      blood glucose (2 h PG), glycosylated hemoglobin (HbA1c)], incidence of
      hypoglycemia, obesity indexes [waist circumference, body mass index (BMI)], blood
      lipid indexes [serum total cholesterol (TC), serum triacylglycerol (TG), low
      density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol
      (HDL-C)], liver and kidney function indexes [serum creatinine (Scr), blood urea
      nitrogen (BUN) and blood uric acid (UA), glutamic-pyruvic transaminase (ALT)] and
      TCM symptom score. The effects and the incidence of type 2 diabetes were
      evaluated. RESULTS: After treatment, 2 h PG and HbA1c reduced in the two groups
      (P<0.01, P<0.05) and the results in the embedding group were better (both
      P<0.05). After treatment, the incidence of hypoglycemia in the embedding group
      was 0.7% (1/150), and that in the western medication group was 1.3% (2/150),
      without statistical difference (P>0.05). After treatment, waist circumference and
      BMI reduced in the two groups (both P<0.01) and the improvements in the embedding
      group were better (both P<0.05). TC, TG and LDL-C after treatment were lower than
      those before treatment, and HDL-C were higher in the two groups (all P<0.05),
      without statistical different values before and after treatment between the two
      groups (all P>0.05). Scr, BUN, UA and ALT before and after treatment in the two
      groups had no statistical difference (all P>0.05), without statistical difference
      after treatment between the two groups (all P>0.05). The TCM score after
      treatment was lower than that before treatment in the embedding group (P<0.05),
      and the difference was not statistical in the western medication group (P>0.05).
      The different value of TCM score in the embedding group was better than that in
      the western medication group (P<0.01). The total effective rate in the embedding
      group was 98.0% (147/150), which was superior to 92.7% (139/150) in the western
      medication group (P<0.05). The incidence of type 2 diabetes was 2.0% (3/150) in
      the embedding group, and that was better than 7.3% (11/150) in the western
      medication group (P<0.05). CONCLUSION: Thumb-tack needle for subcutaneous
      embedding for 2 years could apparent improve the indexes of IGT, which is better
      than western medication, without liver and kidney damage.

PMID- 29354931
TI  - [Shoulder joint pain of rotator cuff injury treated with electroacupuncture and
      Mulligan's mobilization: a randomized controlled trial].
AB  - OBJECTIVE: To verify the clinical therapeutic effects on shoulder joint pain of
      rotator cuff injury treated with electroacupuncture (EA) and Mulligan's
      mobilization. METHODS: A total of 120 patients of shoulder joint pain of rotator
      cuff injury were randomized into an EA group, a rehabilitation group and a
      combined therapy group, 40 cases in each one. In the EA group, EA was applied to
      Jianzhen (SI 9), Jianliao (TE 14), Jianyu (LI 15), Tianzong (SI 11), Jianqian
      (extra) and Binao (LI 14) in the affected side. Of these acupoints, Jianliao (TE
      14) and Jianyu (LI 15), Jianzhen (SI 9) and Tianzong (SI 11) were stimulated with
      Han's electric apparatus. In the rehabilitation group, Mulligan's mobilization
      was used, including scapular mobilization, static joint mobilization and dynamic
      joint mobilization. In the combined therapy group, EA was used in combination
      with Mulligan mobilization. The treatment was given once a day in each group, 5
      sessions a week, totally for 6 weeks. The pain intensity of shoulder joint (VAS),
      the University of California at Los Angeles shoulder rating scale (UCLA) and the
      range of motion (ROM) of shoulder joint were evaluated before and 6 weeks after
      treatment separately. The adverse reactions were recorded in each group. RESULTS:
      VAS scores were all reduced, UCLA scores increased and ROM improved after
      treatment as compared with those before treatment in the patients of the three
      groups (all P<0.05). After treatment, VAS score, UCLA score and ROM in the
      combined therapy group were remarkably improved as compared with those in the EA
      group and the rehabilitation group (all P<0.05). Regarding the improvements of
      VAS and UCLA scores, the results in the EA group were better than those in the
      rehabilitation group (both P<0.05). Regarding ROM improvement, the results in the
      rehabilitation group were superior to those in the EA group (all P<0.05). There
      was no adverse reaction in the two groups. CONCLUSION: The combined therapy of EA
      and Mulligan's mobilization relieves shoulder joint pain of rotator cuff injury,
      better than the simple application of either EA or Mulligan's mobilization.

PMID- 29354932
TI  - [Effects of the combined therapy of heat sensitive moxibustion and acupoint
      injection on endometrial receptivity of hypdrosalphinx infertility in the
      patients after hysteroscopy and laparoscopy].
AB  - OBJECTIVE: To explore the effects of the combined therapy of heat sensitive
      moxibustion and acupoint injection on endometrial receptivity of hypdrosalphinx
      infertility in the patients after hysteroscopy and laparoscopy on the base of
      routine post-operative anti-inflammation. METHODS: A total of 210 patients of
      hypdrosalphinx infertility after hysteroscopy and laparoscopy were divided into a
      combined therapy group, a heat sensitive moxibustion group and a control group,
      70 cases in each one according to the random number table. In the control group,
      the intravenous drip of cefoxitin sodium was adopted, and the anti-inflammation
      treatment was given for 1 week after operation. In the heat sensitive moxibustion
      group, on the basis of the treatment as the control group, the heat sensitive
      moxibustion was applied after vaginal bleeding stopped. The acupoints were
      Yaoyangguan (GV 3), Guanyuan (CV 4), Qihai (CV 6), Shenshu (BL 23), Sanyinjiao
      (SP 6), Yinlingquan (SP 9) and Zigong (EX-CA1). The acupoints were modified
      according to the different syndromes. In the combined therapy group, on the basis
      of the regimen as the heat sensitive moxibustion group, after vaginal bleeding
      stopped, the acupoint injection was given alternatively at bilateral Tiangong
      (extra, 1.0 cm inferior and bilateral to the cervix) with lidocaine 1 mL,
      amikacin 2 mL and salvia injection 2 mL. The treatment was given once every day,
      the treatment for 10 times as one course and a total of 3 courses were required.
      The endometrial type, thickness, uterine arterial plusatility index (PI) and
      resistance index (RI) were observed in the patients of each group. RESULTS: After
      treatment, the numbers of A-type endometrial type in the combined therapy group
      and the heat sensitive moxibustion group were remarkably higher than those of the
      control group [57.1% (40/7) vs 31.4% (22/70), 50.0% (35/70) vs 31.4% (22/70),
      both P<0.05]. The endometrial thickness after treatment was all increased as
      compared with that before treatment in each group (all P<0.05). The increasing
      degree in the combined therapy group was better than either the heat sensitive
      moxibustion group or the control group (both P<0.05). The improvement in the heat
      sensitive moxibustion group was superior to the control group (P<0.05). PI and RI
      in the combination group and PI in the control group were decreased after
      treatment (all P<0.05). The improvements of PI and RI in the combination group
      were better than those in the heat moxibustion group (both P<0.05), which were
      superior to those in the control group (all P<0.05). CONCLUSION: In the patients
      of hypdrosalphinx infertility after hysteroscopy and laparoscopy, the combined
      therapy of heat sensitive moxibustion and acupoint injection increases
      endometrial thickness, reduces uterine arterial resistance and improves
      endometrial receptivity.

PMID- 29354933
TI  - [Clinical therapeutic effects of acupuncture combined with Chinese herbal
      medicine on infertility of polycystic ovary syndrome in the patients with
      ovulation induction with letrozole].
AB  - OBJECTIVE: To evaluate the clinical therapeutic effects and safety on infertility
      of polycystic ovary syndrome (PCOS) in the patients with ovulation induction with
      letrozole in the treatment with the formula for regulating menstruation and
      removing phlegm and electroacupuncture (EA). METHODS: A total of 120 patients of
      PCOS infertility were randomized into 3 groups, 40 cases in each one. In the
      group A, diane-35 was prescribed for oral administration (one tablet a day since
      the 5th day of menstruation, continuously for 21 days). After 1 course of
      treatment (3 months), letrozole was used (one tablet a day since the 5th day of
      menstruation, continuously for 5 days) for ovulation induction for another 1
      course (3 months). In the group B, on the basis of the treatment as the group A,
      since the 5th day of menstruation, the Chinese herbal formula was combined to
      regulate menstruation and remove phlegm, one dose a day and discontinued during
      menstruation. In the group C, on the basis of the treatment as the group B, EA
      was added since the 5th day of menstruation. The main acupoints were Guanyuan (CV
      4), Zusanli (ST 36) and Fenglong (ST 40), etc. EA was applied once every 2 days
      and discontinued during menstruation. In all of the 3 groups, the treatment for 3
      months was as 1 course and the 2 courses were required continuously. Before and
      after treatment, the menstruation improvements, body weight, body mass index
      (BMI), serum sex hormones [luteal production hormone (LH), follicle stimulating
      hormone (FSH), LH/FSH, total testosterone (T) and estradiol (E2)] were observed
      in the patients of each group. The enzyme linked immunosorbent assay was adopted
      to determine the content of anti-mullerian hormone (AMH) and inhibin B (IHNB).
      The therapeutic effects, safety, ovulation rate and pregnancy rate were compared
      among the 3 groups. RESULTS: (1) The differences were significant statistically
      in the total effective rate, ovulation rate and pregnancy rate in comparison of
      the 3 groups (all P<0.05). The results in the group C were the best and those in
      the group B were the better in the comparison of the 3 groups. (2) After
      treatment, the menstrual cycle was remarkably shortened in the 3 groups (all
      P<0.05). The result in the group C was better than that in the group A (P<0.05).
      After treatment, the body weight in the group B and group C was all reduced (both
      P<0.05). The reducing degree in the group C was better than that in the group A
      (P<0.05). The differences in BMI were not significant statistically before and
      after treatment in each group as well as in comparison among the groups (all
      P>0.05). (3) After treatment, the levels of LH and LH/FSH were all reduced
      remarkably in the 3 groups (all P<0.05). The differences were not significant
      statistically in comparison among the three groups (all P>0.05). After treatment,
      in the group B and group C, the levels of T and AMH were all reduced remarkably
      (all P<0.05), in which, T value in the group C was lower than that in the group A
      and group B, that in the group B was lower than the group A (all P<0.05). AMH
      value in the group C was lower than that in the group A (P<0.05). The differences
      were not significant statistically in FSH, E2 and IHNB before and after treatment
      in each group as well as in comparison among the 3 groups (all P>0.05). (4) The
      luteinized unreuptured follicle syndrome (LUFS) did not happen in the group C.
      There were 3 cases of LUFS (7.5%) in the group B and 5 cases (12.5%) in the group
      A. CONCLUSION: For PCOS infertility patients receiving ovulation induction with
      letrozole, the combined treatment with the Chinese herbal formula for regulating
      menstruation and removing phlegm and EA remarkably improves the menstrual cycle,
      reduces body weight and the levels of LH, LH/FSH, T and AMH, improves ovulation
      and pregnancy rates. This therapy does not induce adverse reactions and the
      therapeutic effects are better than the simple application of letrozole or the
      combined therapy of letrozole and Chinese herbal medicine.

PMID- 29354934
TI  - [Application of acupoint massage in postpartum hypogalactia in puerpera].
AB  - OBJECTIVE: To evaluate the effects of acupoint massage for postpartum
      hypogalactia in puerpera. METHODS: A total of 60 puerpera of cesarean section
      were randomized into an observation group and a control group, 30 cases in each
      one. In the observation group, 2 cases were dropped out. Finally, there were 28
      cases in the observation group and 30 cases in the control group. In the control
      group, the routine nursing after operation in obstetrics department was given,
      guiding maternal breastfeeding and postpartum health education. In the
      observation group, on the basis of the treatment as the control group, the
      corresponding acupoints were selected from the breast related meridians for
      massage. Acupoint massage was given since the 3rd day after operation, 8:00 am to
      9:00 am, once a day, 1 min at one acupoint, continuously for 5 days. The
      lactation volume, breast filling, galactostasis and milk viscosity were compared
      in the parturient of the two groups. The clinical therapeutic effects were
      compared between the two groups. RESULTS: From the 1st to the 2nd days, the
      differences were not significant in lactation volume, breast filling and
      galactostasis score between the two groups (all P>0.05). From the 3rd to 5th
      days, the lactation volume, breast filling and galactostasis score in the
      observation group were all lower than those in the control group (all P<0.01).
      The difference in milk viscosity was not significant in the first 4 days between
      the two groups (all P>0.05). On the 5th day, the score of milk viscosity in the
      observation group was lower than that in the control group (P<0.01). The cured
      rate was 64.3% (18/28) in the observation group, which was better than 13.3%
      (4/30) in the control group (P<0.05). CONCLUSION: Massage at the acupoints from
      the breast related meridians effectively promotes the lactation secretion in
      puerpera of postpartum hypogalactia and alleviates breast distention.

PMID- 29354935
TI  - [Efficacy of auricular point sticking therapy for abnormal blink in children and
      impact on the breakup time of tear film].
AB  - OBJECTIVE: To observe the efficacy of auricular point sticking therapy for
      abnormal blink in children and the impact on the breakup time of tear film.
      METHODS: A total of 123 cases (246 eyes) with abnormal blink were randomly
      assigned into two groups, 62 cases (124 eyes) to an observation group, 61 cases
      (122 eyes) to a control group. The observation group received auricular point
      sticking therapy with western medicine; the treatment was given 6 d per week; the
      next day received no treatment and changed dressing. The auricular points were
      yan (LO5), pingjianqian (TG2i), pingjianhou (AT1 i), gan (CO12), pi (CO13), wei
      (CO4). The western medicine pateints took 1 oral multivitamins tablets per day,
      and received sodium hyaluronate eye drops and tobramycin eye drops in turn, 3
      times per day, 7 day as a course; treatment was lasting 3 courses. Patients in
      the control group only received western medicine. The blink frequency score and
      breakup time of tear film of children were observed, the curative effect of the
      two groups was compared. RESULTS: After treatment, the blink frequency score was
      lower significantly (P<0.01), and lower significantly in subjects in the
      observation group compared to those in the control group (P<0.01). After
      treatment, less than 10 s were 51 eyes (41.8%) and greater than 10 s (including
      10 s) were 71 eyes (58.2%) in the 122 eyes from the control group; in the
      observation group, less than 10 s were 13 eyes (10.5%) and greater than 10 s
      (including 10 s) were 111 eyes (89.5%); there was significant difference between
      the two groups (P<0.01). The effective rate of the observation group was 91.9%
      (114/124), which was higher than the control group 65.6% (80/122); the difference
      was statistically significant (P<0.01). CONCLUSION: The efficacy of auricular
      point sticking therapy combine western medicine is better in treating children
      with abnormal blink compared to western medicine by reducing the breakup time of
      tear film. This suggests that reduction of tear film stability is one of the main
      reasons which causes frequent eye blink, and breakup time of tear film can be
      used as the testing standard.

PMID- 29354936
TI  - [Aconite cake-separated moxibustion for knee osteoarthritis with kidney-marrow
      deficiency].
AB  - OBJECTIVE: To observe the effects among aconite cake-separated moxibustion,
      moxibustion and acupuncture for knee osteoarthritis (KOA) with kidney-marrow
      deficiency and to explore the feasibility of cake-separated moxibustion as a home
      remedy solution. METHODS: Ninety patients were randomized into an aconite cake
      separated moxibustion group, a moxibustion group and an acupuncture group, 30
      cases in each one. The acupoints in the three groups were Neixiyan (EX-LE 4),
      Dubi (ST 35) in the affected side, and bilateral Xuehai (SP 10), Liangqiu (ST
      34), Heding (EX-LE 2), Shenshu (BL 23) and Zusanli (ST 36). All the treatment was
      given for 3 sessions, 10 days as a session with 2 to 3 days between 2 sessions,
      and once a day. The first 2 courses of aconite cake-separated moxibustion was
      applied in the hospital and the other 1 session was used at home guided by
      officer physician. Symptoms and physical signs classification score and life
      quality scores were recorded before and after treatment and 6 months after
      treatment, including walking pain, knee pain in stoop and squat, knee discomfort
      in stair activity and daily discomfort. The effects were evaluated. RESULTS: The
      symptoms and physical signs classification scores in the three groups after
      treatment and at follow-up were lower than those before treatment (P<0.01,
      P<0.05), and the scores in the aconite cake-separated moxibustion group were
      better than those in the moxibustion group and acupuncture group (all P<0.01).
      The scores of walking pain, knee pain in stoop and squat, knee discomfort in
      stair activity and daily discomfort were lower in the three groups after
      treatment and 6 months after treatment (P<0.01, P<0.05), and the scores of
      walking pain and daily discomfort in the aconite cake-separated moxibustion group
      were lower than those in the moxibustion group and acupuncture group (P<0.01,
      P<0.05). After treatments, the cured and markedly effective rate in the aconite
      cake-separated moxibustion group was 63.3% (19/30); that in the moxibustion group
      was 50.0% (15/30) and one in the acupuncture group was 43.3% (13/30). The cured
      and markedly effective rate of aconite cake-separated moxibustion group was more
      promising than those in the other two groups (both P<0.05). At follow-up, the
      cured and markedly effective rate in the aconite cake-separated moxibustion group
      was 56.7% (17/30), which was better than 36.7% (11/30) in the moxibustion group
      and 40.0% (12/30) in the acupuncture group (both P<0.05). CONCLUSION: Aconite
      cake-separated moxibustion can be used for KOA patients with kidney-marrow
      deficiency, which can improve patients' life quality and is better than
      moxibustion and acupuncture. The method is feasible as a home remedy solution.

PMID- 29354937
TI  - [Therapeutic effects on cerebral white matter injury of premature infants treated
      with acupuncture for promoting the governor vessel and tranquilizing the mind].
AB  - OBJECTIVE: To explore the repair effects of acupuncture for promoting the
      governor vessel and tranquilizing the mind (acupuncture technique) on cerebral
      white matter injury of premature infants. METHODS: A total of 56 cases of
      cerebral whiter matter injury of premature infants, the fetal age less than 35
      weeks were selected and randomized into an observation group (27 cases) and a
      control group (29 cases). The routine basic rehabilitation therapy was used in
      the two groups. Additionally, in the observation group, the acupuncture technique
      was added, once a day and the treatment for 15 days was as 1 course. Totally, 3
      courses of treatment were required. Before and after treatment, the cranial
      magnetic resonance imaging (MRI) and the diffusion tensor imaging (DTI) were
      adopted to observe the location and severity of cerebral white matter injury. The
      Gesell developmental scale was used to assess the nerve motor development.
      RESULTS: After treatment, the difference was not significant statistically in the
      severity of cerebral white matter injury in the infants between the two groups
      (P>0.05). The FA value of cerebral white matter in the interesting zone was
      increased as compared with that before treatment in the infants of the two groups
      (both P<0.05). The result in the observation group was higher than that in the
      control groups (P<0.05). After treatment, DQ value of each function zone in
      Gesell scale was all increased as compared with that before treatment in the two
      groups (all P<0.05). After treatment, the DQ values of gross motor, fine motor
      and social adaptability in the observation group were higher than those in the
      control group (all P<0.05). After treatment, the difference was not significant
      in DQ value of individual-social and speech behaviors between the two groups
      (both P>0.05). CONCLUSION: Acupuncture technique for promoting the governor
      vessel and tranquilizing the mind promotes the repair of the function in the
      premature infants with cerebral white matter injury and further benefits the
      promotion of the intelligence.

PMID- 29354938
TI  - [Effects of acupuncture at opposite acupoints on expression of hepatocyte growth
      factor in rats with skeletal muscle contusion].
AB  - OBJECTIVE: To observe the effects of acupuncture at opposite acupoints on
      expression of hepatocyte growth factor (HGF) in rats with skeletal muscle
      contusion, and to explore the mechanism of acupuncture at opposite acupoints on
      skeletal muscle contusion. METHODS: Fifty-four Sprague Dawley (SD) rats were
      randomly divided into a blank group (6 rats), a model group (24 rats) and an
      opposing needling group (24 rats). The model group and opposing needling group
      were further divided into 1-day subgroup, 3-day subgroup, 5-day subgroup and 7
      day subgroup, 6 rats in each one. No intervention was given in the blank group,
      while the model of skeletal muscle contusion was established in the model group
      and opposing needling group by self-made contusion device. 24 hours after
      contusion, electroacupuncture (EA) was applied at "Zusanli" (ST 36) and the
      corresponding points of ashi points at health side for 15 min, once a day. The
      subgroups of opposing needling group were treated for 1 day, 3 days, 5 days and 7
      days, respectively. No treatment was given in the model group. Samples were
      collected in the subgroups 1 day, 3 days, 5 days and 7 days after treatment. The
      morphological change of injured gastrocnemius muscle was observed by using
      microscope after HE staining. The positive cell rate of proliferating cell
      nuclear antigen (PCNA) was detected by immunohistochemistry. The expression
      levels of HGF protein and PCNA protein were observed by Western blot. RESULTS: 1
      The results of HE staining showed that, 1 day after contusion, the inflammatory
      cells of gastrocnemius muscle in the opposing needling group were less than those
      in the model group; 3 days and 5 days after contusion, myoblasts and myotubes in
      the opposing needling group were more than those in the model group; 7 days after
      contusion, the neonatal muscle cells in the opposing needling group were more
      than those in the model group. 2 The results of immunohistochemistry showed that,
      1 day, 3 days and 5 days after contusion, the positive cell rate of PCNA in the
      opposing needling group was significantly higher than that in the model group
      (all P<0.001); 7 days after contusion, the positive cell rate of PCNA in the
      opposing needling group was significantly less than that in the model group
      (P<0.001). 3 The results of Western blot showed that, 1 day, 3 days and 5 days
      after contusion, the expression of HGF protein and PCNA protein in the opposing
      needling group was significantly higher than that in the model group (all
      P<0.05); 7 days after contusion, the expression of HGF protein and PCNA protein
      in the opposing needling group was significantly lower than that in the model
      group (all P<0.05). CONCLUSION: Acupuncture at opposite acupoints could regulate
      the expression of HGF and promote the activation, proliferation, migration and
      differentiation of muscle satellite cells in rats with skeletal muscle contusion,
      which could speed up the process of skeletal muscle injury repair.

PMID- 29354939
TI  - [Electroacupuncture at intercostal nerve for mammary gland hyperplasia in rats].
AB  - OBJECTIVE: To explore the correlation between efficacy of electroacupuncture (EA)
      on mammary gland hyperplasia (MGH) and the regulatory pathway of intercostal
      nerve. METHODS: Fifty female SD rats were randomly divided into a blank group
      (group A, 12 rats), a model group (group B, 12 rats), an EA group (group C, 13
      rats) and an intercostal nerve transection group (group D, 13 rats). The rats in
      the group B, group C and group D were prepared into MGH model; after model was
      successfully prepared, the 7th intercostal nerve was cut off in the group D. EA
      was applied at back acupoints including bilateral "Tianzong" (SI 11), "Ganshu"
      (BL 18) and "Shenshu" (BL 23) as well as chest acupoints including bilateral
      "Wuyi" (ST 15), "Hegu" (LI 4) and "Danzhong" (CV 17) in the group C and D. The
      two groups of acupoints were selected alternately. EA was given for 20 min, once
      a day; 5-day treatment was taken as one course; there was an interval of 2 days
      between course; totally 20 treatments were given. After treatment, the height and
      diameter of papilla were observed; the contents of serum estradiol (E2) and
      progestin (P), the expression of estrogen receptor alpha (ERalpha) and
      progestrone receptor (PR) in mammary gland were measured. RESULTS: (1) The height
      and diameter of papilla: after treatment, the height and diameter of papilla in
      the group C were significantly smaller than those in the group B (both P<0.05);
      the height and diameter of left-side papilla in the group D were significantly
      bigger than those in the group C (both P<0.05). (2) Serum E2 and P: after
      treatment, compared with the group B, the contents of E2 and E2/P were reduced
      and the content of P was increased in the group C and group D (all P<0.05).
      Compared with the group C, the contents of E2 and E2/P were increased and the
      content of P was reduced in the group D (all P<0.05). (3) ERalpha and PR in
      mammary gland: compared with the group B, the content of ERalphawas decreased and
      the content of PR was increased in the group C (both P<0.05). Compared with the
      group C, the content of ERalphawas increased and the content of PR was decreased
      in the group D ((both P<0.05). CONCLUSION: The efficacy mechanism of EA for MGH
      is likely to be related with the pathway of intercostal nerve; the mechanism may
      be acupuncture regulating the contents of serum E2 and P as well as contents of
      ERalpha and PR in mammary gland.

PMID- 29354940
TI  - [JI Laixi's experience of acupuncture and moxibustion for knee osteoarthritis].
AB  - In theory of TCM, the root cause of knee osteoarthritis (xibi) is the deficiency
      of liver and kidney, while the symptoms are involved with multiple damages of
      muscles, tendons and joints. The exogenous evil of wind, coldness, dampness and
      heat as well as the blood stasis usually block the meridians and collaterals,
      which cause the knee osteoarthritis. Professor JI Laixi selects acupoints based
      on syndrome differentiation, and treats both root cause and symptoms. He attaches
      importance to the ashi points, and takes pain as acupoints. He also treats the
      lower part of body using the upper acupoints, and treats knees through
      stimulating the low back. The basic acupoints include the affected Dubi (ST 35),
      Yinlingquan (SP 9), Yanglingquan (GB 34), Liangqiu (ST 34), Xuehai (SP 10), Xixia
      point (extral) and ashi point in the knees and waist. Fengchi (GB 20) and Geshu
      (BL 17) are added for the symptom of wind; Guanyuan (CV 4) is added for the
      symptom of coldness; Zusanli (ST 36) is added for the symptom of dampness; Quchi
      (LI 11) is added for the symptom of heat; Fenglong (ST 40) and Sanyinjiao (SP 6)
      are added for the symptom of phlegm-stasis; Ganshu (BL 18) and Shenshu (BL 23)
      are added for the deficiency of the liver and kidney. The technical combination
      of acupuncture, including needle-knife, fire needle, bloodletting, regular
      acupuncture, TDP, are applied to regulate the patients' deficiency and excess
      using the nine-six reinforcing and reducing methods, and pay high attention to
      the mind regulation. Using this method, the efficacy is significant.

PMID- 29354941
TI  - [New thoughts in mechanism research of acupuncture for myocardial stunning from
      kappa-opioid receptor signaling pathway].
AB  - By reviewing the literature regarding the development mechanism of myocardial
      stunning, effects of acupuncture on myocardial ischemic injury, and correlation
      between acupuncture and kappa-opioid receptor, it was suggested that acupuncture
      was highly likely to act on kappa-opioid receptor in myocardial cells, and
      directly treated myocardial malfunction induced by myocardial stunning through
      kappa-opioid receptor and its signaling pathway. In addition, acupuncture could
      inhabit the signaling pathway of adrenoceptor beta1, one of the main functional
      receptors, to indirectly improve myocardial ischemic injury. From kappa-opioid
      receptor signaling pathway, the action mechanism of acupuncture for prevention
      and treatment of myocardial stunning was discussed in this paper, hoping to
      provide new ideas for possible mechanism of acupuncture for myocardial ischemic
      injury.

PMID- 29354942
TI  - [Confounding factors in research for characteristics of acupoint electrical
      impedance].
AB  - The literature regarding the electrical characteristics of acupoints was
      reviewed, and the confounding factors (indoor temperature and humidity, criteria
      of acupoint selection, use of electrical resistance instruments) were summarized
      and analyzed. It was proposed that during the measurement, the indoor temperature
      should be constant and in the state of heat adaptation as much as possible; the
      effects of humidity on resistance value should be reduced to stabilize the heat
      loss of skin through evaporation; the acupoint selection and manipulation should
      be in accordance with agreed standard; attention should be paid to the operation
      and instruction of the instrument, in combination with experiment purpose. As a
      result, the repeatability and reliability of research results of electrical
      characteristics of acupoints could be improved.

PMID- 29354943
TI  - [Analysis on the concepts related to adverse events and adverse reactions of
      acupuncture].
AB  - With the increasing popularity of acupuncture therapy in the world, the safety of
      acupuncture has attracted more attention. The objective and impartial assessment
      of the safety of acupuncture becomes very important. The "adverse events of
      acupuncture" and "adverse reactions of acupuncture" are the common concepts in
      the research of acupuncture safety. In the paper, on the basis of the conceptual
      characteristics of "adverse events" and "adverse reactions" and in combination
      with the particular characteristics of acupuncture itself, the connation and
      features of the concepts of the "adverse events of acupuncture" and "adverse
      reactions of acupuncture" are analyzed. The interaction and differences are
      summarized. Both "adverse events of acupuncture" and "adverse reactions of
      acupuncture" are in the category of adverse medical events. The "adverse events
      of acupuncture" includes the damages induced by acupuncture therapy and also
      those without relationship with acupuncture therapy. The "adverse reactions of
      acupuncture" refers to the adverse outcomes induced by acupuncture therapy
      specially. It has the definite relationship with acupuncture therapy. Hence, the
      application of "adverse reactions of acupuncture" is more objective and accurate
      in the assessment of acupuncture safety.

PMID- 29354944
TI  - [Application of classic Chinese medicine theory in acupuncture CBL teaching
      rounds].
AB  - Teaching rounds is an important part of clinical teaching. It bright the theory
      guide to clinical practice. The classical Chinese medicine theory plays an
      essential role in teaching and clinical practice. During the CBL (case-based
      learning) teaching rounds of acupuncture and moxibustion, by selecting typical
      cases, in combination with directional problem settings, the classical Chinese
      medicine theory is run through the whole process to motivate students'
      initiative, improve teaching quality and promote inheritance and development of
      TCM.

PMID- 29354945
TI  - [Study on the bamboo slips of Maishu in the Han Dynasty excavated in
      Laoguanshan].
AB  - The bamboo slips of medicine, from No. 361 to No. 628, unearthed in Laoguanshan
      are of the same specification, which shall be the same one as Maishu (<<>>) of
      the Han Dynasty from Zhangjiashan in terms of the basic constitution and style.
      Hence, the medical slips, from No. 361 to No. 628, unearthed in Laoguanshan shall
      be titled as Maishu of Laoguanshan version, in which, the text on the "twelve
      meridians" is the combination and adaption from Yinyang Shiyi Mai Jiujiang
      (<<>>Moxibustion Therapy on the Eleven Meridians of Yin and Yang) and Zubi
      Shiyimai Jiujing (<<>>Moxibustion Therapy on the Eleven Meridians of Legs and
      Arms) in the slips of Maishu of the Han Dynasty from Zhangjiashan. The two
      chapters on "derived meridians" have compiled the names, running courses and
      differentiated disorders of the 12 meridians in the different eras at the early
      stage, and in the 9 of these 12 meridians, the prescriptions for moxibustion
      therapy have been attached for the treatment of the differentiated disorders,
      which reflexes the characteristics of mai (meridian) at different evolution
      stages before the formation of the concept of meridian. Regarding the
      descriptions on "pulse diagnostic method", two different methods are included,
      one is relevant with the decision of survival span, and another is with the
      localization of disorders.

PMID- 29354946
TI  - [Mechanisms of acupuncture for non-alcoholic fatty liver disease: researches
      progress and prospects].
AB  - Literature regarding the pathogenesis of non-alcoholic fatty liver disease
      (NAFLD) and the mechanisms of acupuncture for NAFLD published between January of
      2006 to December of 2016 was searched in CBM database, Wanfang database, CNKI
      database and PubMed. After analysis, the possible mechanisms of acupuncture for
      NAFLD were summarized from 5 following aspects: acupuncture regulating lipid
      metabolism and participating lipid metabolism-related signaling pathways,
      acupuncture improving insulin resistance, acupuncture increasing the antioxidant
      levels of liver tissue to improve lipid peroxidation, acupuncture inhabiting the
      expression of inflammatory cytokines, and acupuncture improving the morphology
      and structure of hepatocyte. Based on the characteristics of acupuncture, the
      suggestions and prospects of future research were proposed from the 4 following
      aspects: the specificity and compatibility of acupoint, the treatment timing of
      acupuncture, the stimulus parameter of acupuncture, and the intervention of
      acupuncture combined with dietary control.

PMID- 29354947
TI  - [Discussion on ideological concept implied in traditional reinforcing and
      reducing method of acupuncture].
AB  - The forming and development of traditional reinforcing and reducing method of
      acupuncture was rooted in traditional culture of China, and was based on the
      ancients' special understanding of nature, life and diseases, therefore its
      principle and methods were inevitably influenced by philosophy culture and
      medicine concept at that time. With deep study on Inner Canon of Huangdi and
      representative reinforcing and reducing method of acupuncture, the implied
      ideological concept, including contradiction view and profit-loss view in ancient
      dialectic, yin-yang balance theory, concept of life flow, monophyletic theory of
      qi , theory of existence of disease-evil, yin-yang astrology theory, theory of
      inter-promotion of five elements, were summarized and analyzed. The clarified and
      systematic understanding on guiding ideology of reinforcing and reducing method
      of acupuncture could significantly promote the understanding on principle,
      method, content and manipulation.

PMID- 29354948
TI  - [Elongated needle for post-stroke indigestion].
AB  - OBJECTIVE: To observe the clinical efficacy difference among elongated needle,
      filiform needle and medication for post-stroke indigestion. METHODS: Sixty cases
      of post-stroke indigestion were randomly assigned into an elongated needle group,
      a filiform needle group and a medication group, 20 cases in each one. Acupuncture
      of restoring consciousness and inducing resuscitation and conventional medical
      treatment were applied in the three groups. 125 mm elongated needles were
      perpendicularly inserted at Zhongwan (CV 12), Liangmen (ST 21) and Tianshu (ST
      25) in the elongated needle group; 20 to 30 mm perpendicular filiform at the same
      points in the filiform needle group. All the treatment was given for 4 weeks, 6
      times a week, 1 time a day. Domperidone was prescribed orally in the medication
      group for 4 weeks, 3 times a day and once 10 mg. The indexes were dyspepsia TCM
      symptom score, Liz dyspepsia questionnaire (LDQ), Nepean Dyspepsia Index of
      quality of life (NDLQI), Safety Data Sheet (SDS) self rating scale and side
      effect scale (TESS). The effects were evaluated. RESULTS: The scores of TCM
      symptom, LDQ, SDS scores in the three groups decreased and NDLQI increased after
      7-day, 14-day, and 28-day treatment as compared with those before treatment
      (P<0.05, P<0.01). The TCM symptom score and LDQ score in the elongated needle
      group after 28-day treatment were lower than those in the filiform needle and
      medication groups (P<0.05, P<0.01). The SDS score in the medication group was
      lower than that in the elongated needle and filiform needle group (both P<0.05).
      There were no significant statistical difference for NDLQI score in the three
      groups (P>0.05). The total effective rate was 90% (18/20) in the elongated needle
      group; those in the filiform needle group and medication group were 70% (14/20)
      and 75% (15/20) respectively, indicating statistical significance (P<0.01).
      CONCLUSION: Acupuncture with elongated needle can obviously improve symptoms in
      the patients with post-stroke indigestion, which is better than filiform needle
      and medication.

PMID- 29354949
TI  - [TIE's flying acupuncture for acute cerebral infarction hemiplegia: a randomized
      controlled trial].
AB  - OBJECTIVE: To compare the efficacy difference between TIE 's flying acupuncture
      combined with conventional treatment and conventional treatment alone on acute
      cerebral infarction hemiplegia. METHODS: A total of 120 patients were randomly
      divided into an observation group and a control group, 60 cases in each one. The
      control group was treated with conventional treatment, including anti-platelet
      aggregation, lipid-lowering, formula of traditional Chinese medicine which could
      promote circulation and remove stasis, neurotrophic medication and symptomatic
      treatment; mannitol was used for cerebral infarction with large area or increased
      intracranial pressure. Based on the conventional treatment applied in the control
      group, the observation group was treated with flying acupuncture at the affected
      Jianyu (LI 15), Quchi (LI 11), Shousanli (LI 10), Waiguan (TE 5), Hegu (LI 4),
      Huantiao (GB 30), Biguan (ST 31), Futu (ST 32), Zusanli (ST 36), etc. The
      treatment was given once a day, six days per week, for totally 2 weeks. The
      simplified Fugl-Meyer score, National Institute of Health Stroke Scale (NIHSS)
      and ADL-Bathel index (BI) score were evaluated before and after treatment in the
      two groups. RESULTS: After the treatment, the simplified Fugl-Meyer and BI were
      significantly increased in both groups (all P<0.05), which was significantly
      higher in the observation group (both P<0.05); after the treatment, the NIHSS was
      significantly lowered in both groups (both P<0.05), which was significantly lower
      in the observation group (P<0.05). CONCLUSION: TIE 's flying acupuncture combined
      with conventional treatment were effective for acute cerebral infarction
      hemiplegia, which have better efficacy than conventional treatment on improving
      motor function, neurological deficit and daily living ability, and the pain is
      mild.

PMID- 29354950
TI  - [Effects of acupuncture on circadian rhythm of blood pressure in patients with
      essential hypertension].
AB  - OBJECTIVE: To observe the effects of acupuncture combined with medication on
      circadian rhythm of blood pressure in patients with essential hypertension.
      METHODS: Sixty-four patients of essential hypertension were randomly divided into
      an observation group and a control group, 32 cases in each group. All the
      patients maintained original treatment (taking antihypertensive medication); the
      patients in the observation group were treated with acupuncture method of "Huoxue
      Sanfeng, Shugan Jianpi", once a day, five times per week, for totally 6 weeks (30
      times). The circadian rhythm of blood pressure and related dynamic parameters
      were observed before and after treatment in the two groups. RESULTS: (1) The
      differences of daytime average systolic blood pressure (dASBP), daytime average
      diastolic blood pressure (dADBP), nighttime average systolic blood pressure
      (nASBP) and circadian rhythm of systolic blood pressure before and after
      treatment were significant in the observation group (all P<0.05); the differences
      of circadian rhythm of blood pressure and related dynamic parameters before and
      after treatment were insignificant in the control group (all P>0.05). The nASBP
      and circadian rhythm of systolic blood pressure in the observation group were
      significantly different from those in the control group (all P<0.05). (2) After
      the treatment, the spoon-shaped rate of circadian rhythm of blood pressure in the
      observation group was higher than that in the control group (P<0.05). CONCLUSION:
      The acupuncture combined with medication could effectively improve the circadian
      rhythm of blood pressure and related dynamic parameters in patients with
      essential hypertension.

PMID- 29354951
TI  - [Acupuncture and Chinese medicine of artificial cycle therapy for insulin
      resistance of polycystic ovary syndrome with phlegm damp type and its mechanism].
AB  - OBJECTIVE: To explore the effect difference between acupuncture combined with
      Chinese medicine of artificial cycle therapy on the basis of western medication
      and simple western medication for polycystic ovarian syndrome (PCOS) of phlegm
      damp type with insulin resistance, and to explore its mechanism. METHODS: Sixty
      patients were randomly assigned into an observation group and a control group, 30
      cases in each group. Patients of the control group began to take letrozole and
      metformin orally on the third menstrual day. Patients of the observation group
      were treated with acupuncture combined with Chinese medicine of artificial cycle
      therapy on the basis of the treatment of the control group. The main acupoints
      were Guanyuan (CV 4), Qihai (CV 6) and bilateral Zigong (EX-CA 1), Luanchao
      (Extra), Fenglong (ST 40), Yinlingquan (SP 9), Zusanli (ST 36), Sanyinjiao (SP
      6). Dahe (KI 12) was matched in the follicular phase, and warm acupuncture was
      applied at Guanyuan (CV 4) and Qihai (CV 6); Zhongji (CV 3) and Xuehai (SP 10)
      were matched in the ovulatory phase, and electroacupuncture were used at Qihai
      (CV 6) and Zhongji (CV 3), Xuehai (SP 10) and Yinlingquan (SP 9), 2 Hz and
      continuous wave; The acupoints in the luteal phase were the above main acupoints,
      at the same time, moxibustion was used at Guanyuan (CV 4) and Qihai (CV 6), the
      treatment was given once every other day, 30 min a time. There was no treatment
      in the menstrual phase. Chinese medicine was applied for tonifying kidney and
      nourishing blood, strengthening spleen and eliminating phlegm. The patients of
      the two groups were treated for continuous three menstrual cycles. The indexes
      before and after treatment were detected, including serum microRNA-29 (miR-29)
      expression, TCM symptom score, insulin (INS), blood-sugar content and homeostasis
      model assessment-insulin resistance (HOMA-IR) index, the endocrine hormone values
      of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone
      (T), LH/FSH ratio, prolactin (PRL). The pregnancy rates of the two groups were
      compared. RESULTS: After treatment the expressions of miR-29 and TCM symptom
      scores of the two groups were lower than those before treatment (P<0.01, P<0.05),
      with better results in the observation group (P<0.01, P<0.05). The levels of LH
      LH/FSH and T of the observation group were lower than those before treatment
      (P<0.01, P<0.05), and the T value in the control group decreased after treatment
      (P<0.05). The changes of LH and LH/FSH in the observation group were better than
      those in the control group (both P<0.05). After treatment, The INS, blood-sugar
      content and HOMA-IR were lower than those before treatment in the two groups
      (P<0.05, P<0.01), with better results for INS and HOMA-IR improvements in the
      observation group (both P<0.05). The pregnancy rate in the observation group was
      56.7% (17/30), which was significantly higher than 30.0% (9/30) in the control
      group (P<0.05). CONCLUSION: Acupuncture combined with Chinese medicine of
      artificial cycle therapy can improve the endocrine levels and insulin resistance
      of PCOS with phlegm damp type. At the same time, the pregnancy rate is improved.
      By the view of molecular biology, there may be a pathway trough changing serum
      miR-29 expression.

PMID- 29354952
TI  - [Effects of autologous blood injection at Zusanli (ST 36) on ovarian function in
      patients with primary ovarian insufficiency].
AB  - OBJECTIVE: To observe the effects of autologous blood injection and 0.9% NaCl at
      Zusanli (ST 36) on ovarian function in patients with primary ovarian
      insufficiency. METHODS: Sixty patients with primary ovarian insufficiency were
      randomly divided into an observation group and a control group, 30 cases in each
      one. The patients in the observation group were treated with injection of
      autologous blood at Zusanli (ST 36); the patients in the control group were
      treated with 0.9% NaCl with identical volume at Zusanli (ST 36). Both the
      treatments were given once a week for 3 months. The ovarian function, including
      follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2)
      were tested before treatment, 1 month, 2 months and 3 months after first acupoint
      injection; the endometrial thickness before and after treatment and clinical
      efficacy were compared in the two groups. RESULTS: Compared before treatment, FSH
      was lowered in the observation group after 1-month treatment (P<0.05), while FSH
      and LH were lowered and E2 was increased after 2-month treatment and 3-month
      treatment (all P<0.05). Compared with 1-month treatment, FSH and LH were lowered
      and E2 was increased in the observation group after 2-month treatment and 3-month
      treatment (all P<0.05). Compared with 2-month treatment, FSH was lowered and E2
      was increased in the observation group after 3-month treatment (both P<0.05). The
      differences of all serum tests before and after treatment were insignificant in
      the control group (all P>0.05). The FSH after 1-month treatment, and FSH, LH and
      E2 after 2-month treatment and 3-month treatment in the observation group were
      significantly different from those in the control group (all P<0.05). The
      endometrial thickness after treatment in the observation group was higher than
      that before treatment (P<0.05), while the endometrial thickness after treatment
      in the control group was similar to that before treatment (P>0.05); the
      difference of endometrial thickness before and after treatment in the observation
      group was higher than that in the control group (P<0.05). The clinical effective
      rate was 83.3% (25/30) in the observation group, which was superior to 46.7%
      (14/30) in the control group (P<0.05). CONCLUSION: The autologous blood injection
      at Zusanli (ST 36) can significantly improve ovarian function, promote
      endometrial growth in patients with primary ovarian insufficiency.

PMID- 29354953
TI  - [Clinical observation of wrist-ankle needle therapy combined with patient
      controlled intravenous analgesia for pain after laparoscopic surgery for
      eccyesis].
AB  - OBJECTIVE: To observe the effect difference between wrist-ankle needle therapy
      combined with patient controlled intravenous analgesia (PCIA) and simple PCIA for
      pain after laparoscopic surgery for eccyesis. METHODS: Ninety-eight patients were
      assigned into an observation group and a control group by random number table, 49
      cases in each one. General static inhalation combined anesthesia was used in the
      two groups. Simple PCIA for pain was applied in the control group. Wrist-ankle
      needle therapy at bilateral ankle area 1 and 2 combined with PCIA were
      implemented in the observation group. The pain state of cut was recorded by
      visual analogue scale (VAS) 1 h, 2 h, 6 h, 12 h, 24 h, 36 h and 48 h after
      surgery. The total effective rates and adverse reaction rates within 48 h after
      surgery were compared between the two groups. RESULTS: The VAS scores 6 h, 12 h
      and 24 h after surgery in the observation group were lower than those in the
      control group (all P<0.01), and the scores in the other time points were not
      statistically different (all P>0.05). The total effective rate of the observation
      group was 98.0% (48/49), which was better than 83.7% (41/49) of the control group
      (P<0.05). The adverse reaction rate of the observation group was 12.2% (6/49),
      and that of the control group was 69.4% (34/49), with statistical difference
      (P<0.01). CONCLUSION: Wrist-ankle needle therapy combined with PCIA can
      effectively relieve pain after laparoscopic surgery for eccyesis, and reduce
      adverse reaction rate after surgery.

PMID- 29354954
TI  - [Moderate and severe persistent allergic rhinitis treated with acupoint
      application therapy of the different intensity: a randomized controlled trial].
AB  - OBJECTIVE: To evaluate the clinical therapeutic effects and safety on moderate
      and severe persistent allergic rhinitis treated with acupoint application therapy
      of the different intensity during the dog days. METHODS: One hundred and sixty
      patients of moderate and severe persistent allergic rhinitis were randomized into
      a No.1 treatment group, a No.2 treatment group, a No.3 treatment group and a
      placebo group, 40 cases in each one. The same acupoints were used in the four
      groups, named Dazhui (GV 14), Dingchuan (EX-B1), Feishu (BL 13), Pishu (BL 20),
      Mingmen (GV 4), Gaohuang (BL 43), Shenshu (BL 23) and Qihai (CV 6). In the three
      treatment groups, the fine powder of the ingredients (semen brassicae, radix
      angeliceae, asarum sieboldii, rhizome corydalis) of compound baijiezi formula was
      used. In the No.1 treatment group, the herbal paste (ginger-prepared paste) was
      prepared with ginger juice and the above herbal powder. In the No.2 and No.3
      treatment groups, the herbal paste (honey-prepared paste) was prepared with honey
      with the above herbal powder. In the placebo group, the pseudo-herbal paste of
      the same appearance was prepared with millet powder and distilled water. The
      acupoint application was given for 2 h in the No.1 and No.2 groups and was for 6
      h in the No.3 treatment group and the placebo group. The acupoint application
      therapy was given once every week during the dogdays, continuously for 5 weeks.
      The total nasal symptom score (TNSS), the score of the rhinoconjunctivitis
      quality of life questionnaire (RQLQ) and the count of blood eosinophils (EOS)
      were observed in the patients of the 4 groups before and after treatment. The
      clinical therapeutic effects were compared among the 4 groups. The incidences of
      the skin adverse reactions were observed in each treatment group. RESULTS: After
      treatment, the scores of TNSS and RQLQ were all reduced as compared with those
      before treatment in the three treatment groups (P<0.05, P<0.01), in which, the
      improvements in the No.3 treatment group were better than those in the No.1
      treatment group and the No.2 treatment group (both P<0.05). After treatment, the
      count of EOS was all reduced as compared with that before treatment in the three
      treatment groups (all P<0.05). The differences were not significant statistically
      among the three treatment groups (all P>0.05). The total effective rate was 85.0%
      (34/40) in the No.3 treatment group, better than 76.3% (29/38) in the No.1
      treatment group, 71.8% (28/39) in the No.2 treatment group and 5.0% (2/40) in the
      placebo group (P<0.05, P<0.01). The incidences of the skin adverse reaction in
      the No.3 treatment group and the No.2 treatment group were lower than those in
      the No.1 treatment group (both P<0.01). CONCLUSION: The acupoint application of
      the different intensity relieves the symptoms and improves the living quality in
      the patients of moderate and severe persistent allergic rhinitis. The stimulation
      of the ginger-prepared herbal paste is strong and induces skin blisters after 2 h
      herbal application. The stimulation of the honey-prepared herbal paste is
      moderate and does not induce blisters. The 6 h stimulation of the honey-prepared
      herbal paste is mild and the therapeutic effect is optimal.

PMID- 29354955
TI  - [Acupuncture mainly with "guoyanre" manipulation for amblyopia in children].
AB  - OBJECTIVE: To observe the effect difference between reinforcing-reducing
      manipulation and "guoyanre" manipulation for amblyopia in children. METHODS: A
      total of 68 children patients with amblyopia were assigned into an observation
      group and a control group by random number table, 34 cases (68 eyes) in each one.
      In the observation group, reinforcing-reducing manipulation was used at Yuyao (EX
      HN 4), Taiyang (EX-HN 5), Tongziliao (GB 1), Jingming (BL 1), Cuanzhu (BL 2), and
      Chengqi (ST 1); twirling-reinforcing method was applied at Ganshu (BL 18),
      Shenshu (BL 23), and Guangming (GB 37);"guoyanre"manipulation was applied at
      bilateral Fengchi (GB 20). The acupoints and manipulations in the control group
      were the same as those in the observation group, except Fengchi (GB 20) with
      reinforcing-reducing method. All the treatment was given for 4 courses, 5 times
      as a course and once a day. The vision improvement was observed half a year after
      treatment. RESULTS: The effective rates for ametropic amblyopia in the
      observation and control groups were respectively 92.0% (23/25) and 70.4% (19/27);
      anisometropic amblyopia, 85.7% (18/21) and 55.0% (11/20); strabismic amblyopia,
      66.7% (12/18) and 29.4% (5/17). The effect of each type in the observation group
      was better than that in the control group (all P<0.05). CONCLUSION:
      "Guoyanre"manipulation for amblyopia is superior to reinforcing-reducing method
      and can obviously improve the vision.

PMID- 29354956
TI  - [Chaihu Longgu Muli decoction combined with acupuncture at back-shu points for
      chronic fatigue syndrome].
AB  - OBJECTIVE: To observe the effect difference between Chaihu Longgu Muli decoction
      combined with acupuncture at back-shu points and simple Chaihu Longgu Muli
      decoction for chronic fatigue syndrome. METHODS: Sixty patients were randomly
      assigned into an herbal group and a combination group, 30 cases in each one.
      Simple Chaihu Longgu Muli decoction was used in the herbal group for continuous
      one month, one decoction a day. Based on that in the herbal group, 30 min
      acupuncture was used in the combination group at bilateral Xinshu (BL 15), Feishu
      (BL 13), Pishu (BL 20), Ganshu (BL 18) and Shenshu (BL 23), with acupoints
      according to syndrome differentiation. Acupuncture was given for 3 courses, 10
      times as a course with 3 days between two courses, once a day. Fatigue status was
      evaluated before and after treatment by fatigue scale 14 (FS-14) and self-rating
      anxiety scale (SAS). RESULTS: The FS-14 scores, including body fatigue scores,
      mental fatigue scores and total scores, and SAS scores after treatment were lower
      than those before treatment in the two groups (all P<0.01), with better
      improvements in the combination group (all P<0.01). CONCLUSION: Chaihu Longgu
      Muli decoction combined with acupuncture at back-shu points can improve chronic
      fatigue syndrome, which are better than simple Chaihu Longgu Muli decoction.

PMID- 29354957
TI  - [Effects of fire needle on quality of life in patients with chemotherapy of non
      small cell lung cancer].
AB  - OBJECTIVE: To observe the effect difference between fire needle combined with
      chemotherapy and fire needle on quality of life in patients with chemotherapy of
      non-small cell lung cancer (NSCLC). METHODS: With randomized controlled method, a
      total of 60 patients with chemotherapy of NSCLC were divided into an observation
      group (fire-needle plus chemotherapy group) and a control group (chemotherapy
      group), 30 cases in each one. The observation group was treated with fire needle
      at Sihua points which consisted of Geshu (BL 17) and Danshu (BL 19), combined
      with chemotherapy selected from TP (paclitaxel+cisplatin)/GP
      (gemcitabine+cisplatin)/DP (docetaxel+cisplatin)/NP (vinorelbine+cisplatin) by
      the oncologist according to patients' condition. The fire needle was given once a
      day for 7 days, and chemotherapy was given for 21 days. The control group was
      treated with chemotherapy alone for 21 days. Before and after treatment, response
      evaluation criteria in solid tumors (RECIST) was applied for evaluation, and
      Karnofsky performance status (KPS) and functional assessment of cancer therapy
      lung (FACT-L) were applied for evaluation of quality of life in patients with
      chemotherapy of NSCLC. RESULTS: The effective rate was 20.0% (6/30) and the
      stability rate was 73.3% (22/30) in the observation group, which were
      insignificantly higher than 16.7% (5/30) and 63.3% (19/30) in the control group,
      respectively (both P>0.05). The KPS after treatment was lower than that before
      treatment in the control group (P<0.05); the KPS after treatment was similar to
      that before treatment in the observation group (P>0.05); the KPS in the
      observation group after treatment was higher than that in the control group
      (P<0.05). The total score and each item score of FACT-L after treatment were
      higher than those before treatment in the observation group (all P<0.05); the
      physical score and emotional score of FACT-L after treatment were higher than
      those before treatment in the control group (both P<0.05); the total score,
      physical score, functional score and subscale score in the observation group were
      significantly higher than those in the control group after treatment (all
      P<0.05), while the social/family score and emotional score in the observation
      group were insignificantly higher than those in the control group (both P>0.05).
      The differences of KPS total score before and after treatment in the two groups
      had moderate positive correlation with differences of FACT-L total score
      (P<0.01). CONCLUSION: Fire needle can improve quality of life in patients of
      NSCLC chemotherapy.

PMID- 29354958
TI  - [Action mechanism of acupuncture along meridians on improving energy metabolism
      in cardiomyocytes].
AB  - OBJECTIVE: To explore the protective effect of acupuncture along meridians on
      rats with myocardial ischemia and its effect and action mechanism on
      cardiomyocyte energy metabolism. METHODS: A total of 104 healthy 12-week-old SD
      rats were fed adaptively for 1 week and included into study with no disease
      symptoms observed. Of them, 24 SD rats were selected regardless of gender, and
      were randomly divided into a blank group and a sham operation group, 12 rats in
      each one. The remaining 80 SD rats were treated with ligation of left anterior
      descending coronary artery to establish the model of myocardial ischemia. The
      successful rate of model establishment was 60%, and 48 rats survived. They were
      randomly divided into a model group, an acupuncture along meridian group, an
      acupuncture along another-meridian group and a non-acupoint group, 12 rats in
      each one. The blank group was not treated with operation, but only bundle
      fixation. The sham operation group was treated with sham operation (coronary
      artery was not ligatured). The model group bundle fixation. The acupuncture along
      meridian group were treated with electroacupuncture (EA) at "Neiguan" (PC 6), the
      acupuncture along another-meridian group were treated with EA at "Hegu" (LI 4),
      and the non-acupoints group were treated at a non-acupoint which located in the
      hollow of the 3rd and 4th metatarsal bones of the dorsal foot of fore rate limb.
      Each bundle fixation or EA was given for 30 min, once a day for consecutive 5
      days. The electrocardiogram was tested in all groups; the apoptosis rate of
      cardiomyocytes was detected by Tunel; the contents of ATP, ADP and AMP in
      myocardium were detected by high performance liquid chromatography. RESULTS: The
      ST segment voltage after model establishment was higher than that before modeling
      (all P<0.05). Compared with the model group after intervention, the ST segment
      was elevated in the acupuncture along meridian group, acupuncture along another
      meridian group and non-acupoint group (P<0.01, P<0.05), but the apoptosis rate of
      cardiomyocytes was significantly reduced (all P<0.01). Compared with the
      acupuncture along another-meridian group and non-acupoint group, the apoptosis
      rate of cardiomyocytes in the acupuncture along meridian group was significantly
      decreased (both P<0.01). Compared with the model group after intervention, the
      content of ATP was increased in acupuncture along meridian group (P<0.05);
      compared with the non-acupoint group, the content of ATP was increased in the
      acupuncture along meridian group (P<0.05); compared with the model group, the
      contents of ADP and AMP were reduced in the acupuncture along meridian group,
      acupuncture along another-meridian group and non-acupoint group (all P<0.05); the
      energy charge EC in the acupuncture along meridian group was higher than that in
      the model group (P<0.05). CONCLUSION: Acupuncture along meridians can effectively
      relieve the damage of cardiac muscle tissue; the possible mechanism is to
      increase ATP and reduce ADP, AMP of cardiomyocytes, so EC level is elevated and
      myocardial cell apoptosis is inhibited, leading to protective effect on cardiac
      muscle tissue and cells.

PMID- 29354959
TI  - [Effect of acupuncture on macrophage polarization of white adipose tissue in
      obese mice induced by high-fat diet].
AB  - OBJECTIVE: To observe the effect of acupuncture at acupoints and non-acupoints on
      macrophage polarization of white adipose tissue in obese mice induced by high-fat
      diet(HFD). METHODS: Fifty male C57BL/6 mice were randomly divided into a control
      group (n=10), and other mice were fed with HFD for 16 weeks to establish model.
      Thirty model mice, which were successfully established and continuously fed with
      HFD for 8 weeks, were randomized into a model group, a non-acupoint group and an
      acupuncture group (n=10/group). The mice in the control group were continuously
      fed with common food for 8 weeks. From the second day after model established,
      the mice of the acupuncture group were treated with acupuncture at "Guanyuan" (CV
      4), "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3); the mice of the non-acupoint
      group were treated with acupuncture at two non-acupoints in tail, 15 min a time,
      once a day for 8 weeks. After model establishment and on the second day after the
      last acupuncture treatment, the body weight was recorded. The level of serum
      triglyceride (TG), total cholesterol (TC) in eye socket blood were measured. The
      morphological structure of epididymis white adipose tissue (eWAT) in mice was
      observed by hematoxylin and eosin (HE) staining. The mRNA expressions of
      interleukin-6 (IL-6), monocyte chemotactic protein 1 (MCP-1), tumor necrosis
      factor alpha (TNF-alpha), IL-10, inducible nitric oxide synthesis (iNOS), CD206
      in eWAT of mice were determined with real-time quantitative PCR (RT-qPCR). The
      protein expressions of iNOS and CD206 in eWAT were determined with
      immunohistochemistry staining (IHC). RESULTS: Compared with the control group,
      the body weight in the model, non-acupoint and acupuncture groups increased at
      the 16th and 24th weeks (all P<0.05). Compared with the model group, the body
      weight of the acupuncture group at the 24th week decreased (P<0.05). The serum TG
      and TC in the model group increased compared with those of the control group
      (both P<0.05). The TC in the non-acupoint group decreased (P<0.05), and the TG
      and TC in the acupuncture group decreased compared with those in the model group
      (both P<0.05). Meanwhile, the mRNA expressions of MCP-1, TNF-alpha, IL-6 and iNOS
      in the model and non-acupoint groups increased compared with those in the control
      group (all P<0.05), and the mRNA expressions of IL-10 and CD206 decreased (all
      P<0.05). The mRNA expressions of MCP-1, TNF-alpha, IL-6 and iNOS in the
      acupuncture group were lower than those in the model group (all P<0.05), and the
      mRNA expressions of IL-10 and CD206 were higher (both P<0.05). HE staining showed
      alveolate adipose tissue in the control group with numbers of unilocular adipose
      cells, vacuolar polygon or circle. The adipose cells in the model group were
      larger and irregular with larger intercellular space. The adipose cells in the
      acupuncture group were minified with smaller intercellular space. Compared with
      those in the control group, the protein expressions of iNOS increased (both
      P<0.05) and those of CD206 decreased (both P<0.05) in the model and non-acupoint
      groups. Compared with those in the model group, the protein expression of iNOS
      decreased (P<0.05) and that of CD206 increased (P<0.05) in the acupuncture group.
      CONCLUSION: Acupuncture can improve inflammation of obese mice through affecting
      macrophage polarization of white adipose tissue.

PMID- 29354960
TI  - [Role of pressing hand in the clinical practice of acupuncture].
AB  - The importance of pressing hand in clinical practice of acupuncture was explored
      in this paper. Through literature review and clinical experience, the role of
      pressing hand before, during and after acupuncture was summarized and analyzed.
      Before acupuncture, the pressing hand helped to diagnose diseases, examine pulse
      and locate acupoints; during acupuncture, it participated in needle insertion and
      reinforcing-reducing manipulation; after acupuncture, it played a role in needle
      withdrawal and regulate human body. It is indicated the pressing hand is a key
      role not only during acupuncture or reinforcing-reducing manipulation, but also
      participates in the overall process of acupuncture, which has great significance
      in guiding clinical treatment and enhancing practice level.

PMID- 29354961
TI  - [Relationship between needling layers and needling sensations in acupuncture].
AB  - Based on the sancai (literally three talents referring to "earth", "human" and
      "heaven") and wuti (literally five organs referring to skin, muscle, vessel,
      tendon and bone, which correspond to five internal organs: lungs, spleen, heart,
      liver and kidney respectively) in Neijing (Internal Classic), as well as the
      tissue structure theory of modern anatomy, and in combination with the clinical
      practice of acupuncture by the author in the past over 30 years, it is proposed
      that four layers are divided in needling depth of acupuncture. The different
      needling sensations are induced at different layers. The first layer is the skin.
      When the needle is inserted into the skin, the main sensation is "pain". The
      second layer is the subcutaneous layer (superficial fascia). The needle tip at
      this layer generates a strong "swelling" sensation, which radiates along a
      certain direction. The third layer is the deep fascia and muscle layer. If the
      needle tip touches the deep fascia, there is a "heavy" feeling. If the needle tip
      goes into the muscle, an "acid" sensation will occur. The fourth layer is the
      periosteum and bone layer, which produces a strong sensation of "pain" when
      touched by the needle tip. In addition, each layer has blood vessels and nerve
      distribution. When the needle tip touches the blood vessels, a sense of "pain"
      happens. If the needle tip touches the nerve, there will be a sensation of
      numbness, which spreads along the direction of nerve conduction. On the contrary,
      through the patient's needling sensations, we can roughly know which layer and
      direction the needle tip goes. Better understanding of the relationship between
      the needling layers and needling sensations contributes to the further study of
      needling techniques, therapeutic effects of acupuncture and patient's sensations.
      It is significant for the regulations of needling sensations in patients.

PMID- 29354962
TI  - [Professor WANG Fuchun's experience in the acupoint selection of clinical
      treatment with acupuncture and moxibustion].
AB  - Professor WANG Fuchun's experience in the acupoint selection of clinical
      treatment with acupuncture and moxibustion was summarized. The main acupoints are
      selected by focusing on the chief symptoms of disease, the supplementary points
      are selected by differentiating the disorders. The acupoints are modified in
      terms of the changes of sickness. The effective acupoints are selected flexibly
      in accordance with the specific effects of points. The summary on the acupoint
      selection reflects professor WANG Fuchun's academic thoughts and clinical
      experience and effectively instructs the clinical practice of acupuncture and
      moxibustion.

PMID- 29354963
TI  - [Quantitative study of meridian topology model based on acupoint-symptom
      relationship].
AB  - Meridian theory plays an important role in the guidance of clinical practice of
      acupuncture and moxibustion. Since the publication of Zhenjiu Jiayi Jing (A-B
      Classic of Acupuncture and Moxibustion), the meridian theory has been developed.
      In the paper, in view of complex science, the topological properties of acupoint
      symptom network were analyzed quantitatively by taking acupoint as node and
      indication as the connection, such as high clustering coefficient and the small
      world effect. It was the first time to give the abstraction for the topological
      proof of the high efficiency information transmission property of acupoint
      symptom network meridian system at different times. Its quantitative and
      digitalized significance was analyzed on the development of meridian theory under
      the complex scientific background so as to provide a new thought and method for
      the study of meridian theory and acupuncture modernization.

PMID- 29354964
TI  - [Discussion on quantum entanglement theory and acupuncture].
AB  - The quantum entanglement is a new discovery of modern physics and has drawn a
      widely attention in the world. After learning the quantum entanglement, the
      authors have found that many characteristics of quantum are reflected in TCM,
      acupuncture theory and clinical practice. For example, the quantum entanglement
      phenomenon is mutually verified with the holism, yinyang doctrine, the theory of
      primary, secondary, root and knot in TCM, etc. It can be applied to interpret the
      clinical situations which is difficult to be explained in clinical practice, such
      as the instant effect of acupuncture, multi-point stimulation in one disorder and
      the points with specific effects. On the basis of the discovery above, the
      quantum entanglement theory achieved the mutual treatment among the relatives in
      acupuncture clinical practice and the therapeutic effects were significant. The
      results suggest that the coupling relationship in quantum entanglement presents
      between the diseases and the acupoints in the direct relative. The authors
      believe that the discovery in this study contributes to the exploration on the
      approaches to the acupuncture treatment in clinical practice and enrich the ideas
      on the disease prevention.

PMID- 29354965
TI  - [Comments on "Effect of acupuncture and clomiphene in Chinese women with
      polycystic ovary syndrome: a randomized clinical trial" published in Journal of
      the American Medical Association].
AB  - In recent years, more and more patients of polycystic ovary syndrome (PCOS) have
      strong desire to be treated with acupuncture. In "Effect of acupuncture and
      clomiphene in Chinese women with polycystic ovary syndrome: a randomized clinical
      trial" published in Journal of the American Medical Association (JAMA) on June
      27, 2017, the finding of this research does not support acupuncture for such
      infertility women. The questions and doubts are proposed in the paper from the
      regimen of acupuncture treatment, the determination of primary outcome and the
      explanation of the results. It is found by comparison that the trigger point
      treatment in the article is different from traditional acupuncture, there is
      doubt in live birth rate as the primary outcome, 4-month treatment is not enough
      for the change of live birth rate, difference without statistic significance
      between acupuncture and control acupuncture does not mean invalid acupuncture
      because the control acupuncture is not invalid, the research and statistic method
      are not those planned. As a result, we consider that the conclusion is
      unreasonable.

PMID- 29354966
TI  - [Evolvement of the expression of fourteen-meridian-acupoint verse and its
      content].
AB  - Through summarizing the meridian verses and acupoint verses of fourteen
      meridians, in views of the expression mode and content evolvement, the academic
      characteristics of fourteen-meridian-acupoint verse were discussed. Regarding the
      expression mode, three are the meridian based verse and the location-meridian
      based verse. Regarding the content evolvement, the changes in the basic content,
      the numbers of meridian points and the sequence of points distribution were
      reflected at different stages during the development of meridian and point
      theory. The fourteen-meridian-acupoint verse is easily to be recited due to its
      language characteristics. It plays an active role in the promotion of the verse
      during the development of meridian and point theory and provides the reference to
      the study on the meridian and point theory and acupuncture education.

PMID- 29354967
TI  - [Research status of the effect mechanism on catgut-point embedding therapy].
AB  - This paper aims to review the research status of the effect mechanism of catgut
      embedding therapy. The literature was retrieved from China Academic Journal
      Network Publishing Database with the keywords as "catgut-point embedding"
      "embedding", dated from the database establishment to December 2015. Totally,
      over 5 000 papers had been collected. It was summarized that TCM effect mechanism
      of catgut-point embedding therapy includes the effects of needle retaining and
      embedding, harmonizing yin and yang, balancing zangfu organs, promoting meridian
      qi, regulating qi and blood, tonifying for the deficiency and reducing for the
      excess, strengthening the antipathogenic qi and eliminating pathogens. From the
      point of view of western medicine, the effect mechanism of catgut-embedding
      therapy refers to recovering nerve function, regulating neural reflex, increasing
      human immunity, improving local circulation, inhibiting the release of
      inflammatory factors, reducing apoptosis, regulating cellular factor and
      improving body metabolism. It was found that the effects of catgut-embedding
      therapy were not only related to the effects induced by common acupuncture, but
      also to the persistent treatment through prolonged stimulation duration,
      especially in the treatment of chronic diseases with many systems involved. This
      therapy reduces or complements to the use of western medicine to certain extent.
      However, the longitude theoretic study on the catgut-embedding therapy is
      limited; the specific statement is less predominant and the clinical controlled
      trial is insufficient at present. Hence, further studies are requested.

PMID- 29354968
TI  - [Kinetic mechanism of electroacupuncture for stair climbing in knee
      osteoarthritis patients].
AB  - OBJECTIVE: To observe the kinetic change that reflects joint loading in different
      planes during stair climbing in knee osteoarthritis (KOA) after
      electroacupuncture (EA) by three-dimensional motion analysis, so as to provide
      reference for its biomechanical mechanism treated with acupuncture. METHODS:
      Forty KOA patients, in accordance with the random number table, were assigned
      into an observation group and a control group, 20 cases in each one and finally
      18 cases completed. Acupoints in the observation group were Neixiyan (EX-LE 4),
      Dubi (ST 35), Yanglingquan (GB 34), Yinlingquan (SP 9), Xuehai (SP 10), Liangqiu
      (ST 34) and Zusanli (ST 36); points in the control groups were located about 2 cm
      next to the above acupoints with shallow acupuncture. EA was connected at
      Neixiyan (EX-LE 4) and Yinlingquan (SP 9), Liangqiu (ST 34) and Yanglingquan (GB
      34). The frequency was 2 Hz with continuous wave in the observation group and
      there was no current in the control group for the corresponding points. All the
      treatment was given for 3 weeks, totally 11 times. Climbing stairs gait was
      measured before and after treatment. Velocities and kinetic parameters during
      ascending and descending stairs were analyzed, including flexion and extension
      peak torques of hip, knee, ankle on the vertical plane, external knee adduction
      moment on the coronal plane. RESULTS: After treatment in the observation group,
      velocities during ascending and descending stairs significantly increased
      (P<0.05, P<0.01); maximal ankle plantar flexor moments during ascending and
      descending stairs and the second peak external knee adduction moment (PEKAM2)
      during ascending stairs significantly increased (P<0.05, P<0.01). After treatment
      in the control group, the first peak external knee adduction moment (PEKAM1) and
      PEKAM2 during descending stairs were less than those before treatment (P<0.05,
      P<0.01). In the observation group, the difference value (DV) of velocity before
      and after treatment was positively correlated to DV in the torque of ankle
      plantar flexors during ascending stairs in the observation group
      (r=0.598,P<0.01). Excluding the impact of velocity, the DV of the maximal torque
      of ankle plantar flexors during ascending stairs didn't show difference in the
      observation group (P>0.05). CONCLUSION: EA can increase the velocities of
      ascending and descending stairs of KOA patients. It improves the loading capacity
      of knee joint on both sagittal and coronary planes. But its effect during
      ascending may be correlated with the increase of velocity. The mechanism of
      different effects between EA and minimal acupuncture on joint moments is still
      unclear and warrants further study.

PMID- 29354969
TI  - [Therapeutic effect observation of post-stroke shoulder pain treated with the
      touching-periosteum needling technique of the meridian muscle region theory].
AB  - OBJECTIVE: To evaluate the pain severity, the motor function of the upper limb
      and the quality of life in the patients of post-stroke shoulder pain treated with
      the touching-periosteum needling technique of the meridian muscle region theory.
      METHODS: One hundred and six cases of post-stroke shoulder pain were randomized
      into an observation group and a control group, 53 cases in each one. In the
      observation group, the touching-periosteum needle technique and the
      rehabilitation training were used on the bases of the theory of meridian muscle
      region. The points were Jianyuci, Binaoci, Jianliaoci, Jianqianci, Quchi (LI 11),
      Shousanli (LI 10) and Waiguan (TE 5) on the affected side. The needles were
      inserted obliquely, at 45 degrees degrees at those extra points to the tendon
      knots till the needle tips touching periosteum. The needles were manipulated to
      ensure the qi arrival and then retained for 30 min. The rehabilitation was
      applied, such as the anti-spasmodic posture, bridge-style movement on the bed,
      weight transition and balance training, joint activity maintenance training,
      passive and active movement of shoulder joint, the training for activities of
      daily living (ADL) and Bobath technique. In the control group, the routine
      acupuncture and the rehabilitation training were used. The acupints were Jianyu
      (LI 15), Binao (LI 14), Jianliao (TE 14), Jianqian (Extra), Quchi (LI 11),
      Shousanli (LI 10) and Waiguan (TE 5). The rehabilitation training was the same as
      the observation group. The treatment was given once every day, 6 treatments a
      week. After 20 treatments, the visual analogue scale (VAS), Fugl-Meyer (FMA)
      score and Barthel (MBI) score were adopted to evaluate the pain severity, the
      motor function of the upper limb and the ADL. The clinical therapeutic effects
      were evaluated in the two groups. RESULTS: The VAS scores were reduced after
      treatment as compared with those before treatment in the two groups, and FMA and
      MBI scores were all increased as compared with those before treatment, indicating
      the significant difference statistically (P<0.05, P<0.01). After treatment, the
      improvements in the observation group were better than those in the control group
      (all P<0.05). The curative and remarkably effective rate was 69.8% (37/53) in the
      observation group, better than 47.2% (25/53) in the control group (P<0.05).
      CONCLUSION: The touching-periosteum needling technique of the meridian muscle
      region theory obviously improves the pain severity, the motor function of the
      upper limb and the quality of life in patients of post-stroke shoulder pain. The
      therapeutic effects are better than the routine acupuncture.

PMID- 29354970
TI  - [Clinical study on post-stroke urinary retention treated with acupuncture at the
      twelve jing-well points and bladder function training].
AB  - OBJECTIVE: To explore the methods for the therapeutic effect improvement in the
      treatment of post-stroke urinary retention. METHODS: Sixty-three patients of post
      stroke urinary retention were randomized into an observation group (32 cases) and
      a control group (31 cases). The routine clinical medication of neurology and
      basic rehabilitation were adopted in the two groups. Additionally, in the control
      group, the intermittent urinary catheterization and bladder function training
      were applied. The duration and frequency of catheterization were determined by
      the autonomic urination and residual urine volume every day. In the observation
      group, on the basis of the treatment as the control group, acupuncture was
      applied to the twelve jing-well points in the sequence of qi flowing among the
      twelve meridians [Shaoshang (LU 11), Shangyang (LI 1), Lidui (ST 45), Yinbai (SP
      1), Shaochong (HT 9), Shaoze (SI 1), Zhiyin (BL 67), Yongquan (KI 1), Zhongchong
      (PC 9), Guanchong (TE 1), Zuqiaoyin (GB 44) and Dadun (LR 1)]. Acupuncture was
      given once a day, 20 treatments were required. In 20 treatments, the clinical
      therapeutic effects and the residual urine volume were observed. RESULTS: The
      total effective rate was 90.6% (29/32) in the observation group, better than
      67.7% (21/31) in the control group (P<0.01)). After treatment, the residue urine
      volume was all reduced apparently in the patients of the two groups (both
      P<0.01). The result of the residue urine volume in the observation group was
      lower apparently than that in the control group (P<0.01). CONCLUSION: Acupuncture
      at the jing-well points in the sequence of qi flowing among meridians combined
      with bladder function training achieve the apparent therapeutic effects on post
      stroke urinary retention. The results are better than those achieved by the
      routine western medicine with bladder function training involved.

PMID- 29354971
TI  - [Flipping moxibustion of Hui medicine combined with western medication for
      rheumatoid arthritis with cold dampness bi syndrome].
AB  - OBJECTIVE: To compare the effects of flipping moxibustion of Hui medicine
      combined with western medication and simple western medication for rheumatoid
      arthritis with cold dampness bi syndrome. METHODS: Eighty patients were randomly
      assigned into an observation group and a control group, 40 cases in each group.
      Oral methotrexate (1 time a week) and sulfasalazine (twice a day except the day
      for methotrexate) were used in the two groups. Patients in the observation group
      were treated with flipping moxibustion of Hui medicine, twice a week. The main
      acupoints were Shenshu (BL 23), Guanyuan (CV 4), Zusanli (ST 36), Yinlingquan (SP
      9), and the matching acupoints were in the meridians related to the disease
      location. All the treatment was given for continuous 4 weeks. The TCM symptom
      score, visual analogue scale (VAS) score, blood sedimentation (ESR), rheumatoid
      factor (RF) and C-reactive protein (CRP) were observed before and after
      treatment. The effect was evaluated. RESULTS: The total effect rate in the
      observation group was 95.0% (38/40), which was better than 77.5% (31/40) in the
      control group (P<0.05). After treatment, the VAS score, TCM symptom score, RF,
      ESR, CRP levels decreased in the two groups (all P<0.05), with better effects in
      the observation group (all P<0.05). The adverse reactions in the observation
      group were lower than those in the control group. CONCLUSION: Flipping
      moxibustion of Hui medicine combined with western medication for rheumatoid
      arthritis with cold dampness bi syndrome are better than simple western
      medication, which are safer and more effective.

PMID- 29354972
TI  - [Therapeutic effect observation of chronic knee joint pain assisted with the
      central-square needling technique of the thumb-tack needles].
AB  - OBJECTIVE: To compare the differences in the clinical therapeutic effects on
      chronic knee joint pain between the combination of the central-square needling
      technique of thumb-tack needles with the routine therapy of acupuncture,
      moxibustion and tuina and the routine therapy of acupuncture, moxibustion and
      tuina. METHODS: One hundred and twenty patients of chronic knee joint pain were
      randomized into an observation group and a control group, 60 cases in each one.
      In the control group, the routine therapy of acupuncture, moxibustion and tuina
      was adopted. In the observation group, at the end of treatment with the routine
      therapy of acupuncture, moxibustion and tuina, the subcutaneous embedding therapy
      was followed with four thumb-tack needles at the sites 1 to 1.5 cm above, below
      and bilateral to the main point (ashi point) separately, and the needles were
      retained for 24 h to 48 h. The treatment was given once every two days, three
      times a week, totally 6 times in two weeks; and the follow-up visit was done for
      3 months in patients of the two groups. The visual analogue scale (VAS) score
      before and after each treatment, Lequesne index score before treatment and at the
      end of follow-up and the case numbers of proactive use of painkillers or
      receiving acupuncture treatment in the follow-up stage were compared and observed
      in the patients of the two groups. RESULTS: The VAS score was reduced gradually
      after treatment in the patients of the two groups. The differences were
      significant statistically after the second treatment as compared with those
      before the treatment in the two groups (all P<0.05), in which, the improvements
      in VAS scores after the third treatment in the observation group were more
      obvious than those in the control group (all P<0.05). At the end of follow-up
      visit, Lequesne index scores were all improved as compared with those before
      treatment in the two groups (both P<0.05) and the improvements were similar
      between the two groups (P>0.05). In the follow-up stage, there were 0 case in the
      observation group and 9 cases in the control group in terms of proactive use of
      painkillers (P<0.05). There were 5 cases in the observation group and 1 case in
      the control group receiving acupuncture treatment again (P>0.05). CONCLUSION: The
      acupuncture scheme in assistance with the central-square needling technique of
      thumb-tack needles obviously relieves chronic knee joint pain, much better
      sustains the analgesic effects of acupuncture and improves patient compliance.

PMID- 29354973
TI  - [Effects of ginger-separated moxibustion at Baliao points combined with Bushen
      Huoxue formula on patients with decreased ovarian reserve function].
AB  - OBJECTIVE: To compare the efficacy differences between ginger-separated
      moxibustion at Baliao points combined with Bushen Huoxue formula and Bushen
      Huoxue formula alone on patients with decreased ovarian reserve function.
      METHODS: Fifty patients of decreased ovarian reserve function were randomly
      divided into an observation group and a control group, 25 cases in each one. The
      patients in the observation group were treated with ginger-separated moxibustion
      at Baliao points combined with Bushen Huoxue formula; the moxibustion was given
      for 1.5 h, once every seven days, and no treatment was given during menstrual
      period. The patients in the control group were treated with Bushen Huoxue
      formula. One-month treatment was taken as one treatment course, and totally three
      courses were given. The change of follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), estradiol (E2), anti-mullerian hormone (AMH), antral follicle count
      (AFC), peak systolic velocity (PSV), resistance index (RI) were observed before
      and after treatment in the two groups. RESULTS: After treatment, the FSH, FSH/LH
      and RI were significantly lowered, but the E2, AFC, PSV were significantly
      increased in the two groups (all P<0.05); the FSH, FSH/LH and E2 in the
      observation group were lower and AFC was higher than those in the control group
      (all P<0.05). CONCLUSION: The ginger-separated moxibustion at Baliao points
      combined with Bushen Huoxue formula are superior to Bushen Huoxue formula alone
      in improving ovarian reserve function.

PMID- 29354974
TI  - [Acupuncture with regulating menstruation to promote pregnancy for diminished
      ovarian reverse: a prospective case series study].
AB  - OBJECTIVE: To investigate the effect and safety of acupuncture with regulating
      menstruation to promote pregnancy for diminished ovarian reverse (DOR). METHODS:
      According to prospective case series, 46 patients were observed and finally 40
      cases were included. The acupoints were 1 Baihui (GV 20), Shenting (GV 24),
      Guanyuan (CV 4) and bilateral Benshen (GB 13), Huangshu (KI 16), Dahe (KI 12),
      Luanchao (Extra), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Taichong (LR
      3) and 2 bilateral Shenshu (BL 23) and Ciliao (BL 32). The points in the two
      groups were used alternately. Acupuncture was given for 3 courses, 12 times as a
      course and 3 times a week. Before and after treatment, and 3 months after
      treatment, follicle-stimulating hormone (FSH), follicle-stimulating
      hormone/luteinizing hormone (FSH/LH), estradiol (E2), antral follicle count (AFC)
      and TCM symptom score were observed. The safety was evaluated. RESULTS: Compared
      with before treatment, the levels of FSH, FSH/LH decreased, and the levels of E2
      and AFC increased after treatment and at follow-up (all P<0.05). And the TCM
      symptom scores were significantly lower than those before treatment (both
      P<0.05). The rate of pregnancy after treatment was 15% (6/40). There was no
      infection and organ injury. CONCLUSION: Acupuncture with regulating menstruation
      to promote pregnancy can safely improve the ovarian reserve of patients with DOR.

PMID- 29354975
TI  - [Comparison effects of acupuncture at distal acupoints and local acupoints on
      treatment of xerophthalmia].
AB  - OBJECTIVE: To compare the clinical efficacy differences between acupuncture at
      distal acupoints and local acupoints on treatment of xerophthalmia. METHODS: A
      total of 40 patients of xerophthalmia were randomly divided into a distal group
      and a local group, 20 cases in each one. One patient in local group lost contact,
      and finally 20 cases in the distal group and 19 cases in the local group finished
      treatment. The patients in the distal group were treated with acupuncture at
      Guangming (GB 37) and Diwuhui (GB 42), while those in the local group were
      treated with acupuncture at Cuanzhu (BL 2), Tongziliao (GB 1) and Taiyang (EX-HN
      5). Patients in both groups were treated once a day, five times per week, and
      totally 2-week treatment were given. The subjective symptom based on visual
      analogue scale (VAS), tear secretion, ocular surface disease index (OSDI) and
      breakup time (BUT) were evaluated before treatment, after two-week treatment (end
      of treatment) and two weeks after end of treatment (follow-up visit) in the two
      groups. RESULTS: After treatment and follow-up visit, the VAS, tear secretion,
      OSDI and BUT were all improved (P<0.05, P<0.01), but the differences of VAS and
      OSDI between the two groups were not significant (both P>0.05). At follow-up
      visit, the differences of tear secretion and BUT between the two groups were
      significant (both P<0.05). CONCLUSION: The acupuncture at distal acupoints could
      relieve xerophthalmia symptoms, improve quality of life, increase tear secretion
      and prolong BUT, which is superior to local acupoints in long term.

PMID- 29354976
TI  - [Relationship between opposite acupoints and acupoint effect from acupoint effect
      of Sanyinjiao (SP 6)-Xuanzhong (GB 39)].
AB  - The acupoint effect of Sanyinjiao (SP 6) and Xuanzhong (GB 39) as well as the
      internal relation of Sanyinjiao (SP 6)-Xuanzhong (GB 39) were analyzed in this
      paper to explore the relationship between opposite acupoints and acupoint effect.
      It was found both Sanyinjiao (SP 6) and Xuanzhong (GB 39) had acupoint effects,
      and the two acupoints had close relationship in acupoint effects (specificity
      along meridian and specificity of acupoints), acupoint-meridian relationship
      (anatomical locations, meridians and organs, indications). It is indicated the
      opposite acupoint of Sanyinjiao (SP 6)-Xuanzhong (GB 39) had related aspects in
      acupoint effects, which is related with acupoint effect through specificity and
      relationship of acupoint-meridian.

PMID- 29354977
TI  - [Ancient identification and modern categorization of the governor vessel
      disorders].
AB  - The ancient and modern literature relevant with the governor vessel disorders is
      collected systematically and their connotation is reconstructed. After the
      collection and analysis on the ancient and modern medical books and literature
      relevant with the governor vessel disorders, it is discovered that the governor
      vessel disorders in the ancient time are relevant with the running course of the
      governor vessel, organs and dysfunction. While the governor vessel disorders in
      modern time are involved with the spine, nerve, respiration, digestion, urinary
      reproduction, head, face and five sensory organs, etc. No matter in the ancient
      times or in the modern times, the recognition on the connotation and
      categorization of the governor vessel are highly similar. In comparison between
      the governor vessel disorders and the spinal disorders, it is believed that they
      are possibly the two concepts with the high similarity between the different
      medical backgrounds of the East and the West.

PMID- 29354978
TI  - [Effects of moxibustion on Treg/Th17 cell and its signal pathway in mice with
      rheumatoid arthritis].
AB  - OBJECTIVE: To observe the effects of moxibustion on Treg/Th17 imbalance and
      related signal pathway in mice with rheumatoid arthritis (RA), so as to explore
      the action mechanism of moxibustion on RA. METHODS: Twenty-four DBA/1J male mice
      were randomly divided into a normal group, a model group, a sham moxibustion
      group and a moxibustion group, 6 mice in each one. RA model was induced by
      subcutaneous injection of typeIIcollagen and adjuvant at tail in mice other than
      the normal group. The mice in the moxibustion group were treated with moxibustion
      at"Zusanli" (ST 36) and "Shenshu" (BL 23), 1 mg per cone, 6 cones per acupoint.
      The consecutive 6-day treatment was taken as one course, and totally 2 courses
      were given with an interval of 2 d between courses. The mice in the sham
      moxibustion group were treated with immobilization as the moxibustion group. The
      effects of moxibustion on joint swelling was evaluated by RA scale of collagen
      induced arthritis (CIA); the pathological changes of joint inflammation were
      observed by HE staining; the cell count of Th17 and Treg in spleen was analyzed
      by flow cytometry; the content of cytokine IL-1beta, IL-6, IL-10, IL-17, IL-23,
      TGF-beta and Galectin-9 were analyzed by ELISA; the mRNA and protein expression
      of Foxp3, Galectin-9, RORgammat, CARMA1, NF-kappaB were analyzed by Real-time PCR
      and Western Blotting method. RESULTS: Ten to 12 d after the secondary immune, red
      and swelling of ankle joint, feet and toe joint were observed, indicating
      successful establishment of RA model. 15 d into moxibustion treatment, the joint
      swelling was improved in the moxibustion group and the sham moxibustion group,
      which was superior in the moxibustion group (P<0.05). As for pathological
      changes, compare with the normal group, the articular surface was rougher and
      synovial layer thinner in the model group, which was recovered to a certain
      extent in the sham moxibustion group; the articular surface was smooth and
      synovial layer was thicker in the moxibustion group, which was similar to the
      normal group. The results of flow cytometry test indicated the cell count of Treg
      in the model group was reduced but that of Th17 was increased than the normal
      group (both P<0.01); the moxibustion could increase significantly the cell count
      of Treg (P<0.05), but no effect was observed on Th17 (P>0.05). The results of
      ELISA test indicated the differences of increasing of IL-1beta, IL-6, IL-17, IL
      23, TGF-betaas well as the reducing of IL-10 were not significant between the
      sham moxibustion group and the moxibustion group (all P>0.05); moxibustion
      treatment could increase the content of Galectin-9 which was reduced in RA mice
      (P<0.05). The results of RT-PCR and Western blotting test indicated the mRNA and
      protein expression of Foxp3, Galectin-9 were reduced in the model group (all
      P<0.01), which could be up-regulated by moxibustion treatment (P<0.05, P<0.01);
      the mRNA and protein expression of RORgammat, CARMA1, NF-kappaB was increased
      (all P<0.01), which could be down-regulated by moxibustion treatment (P<0.05,
      P<0.01). CONCLUSION: Moxibustion could improve the swelling of joint and
      inflammatory reaction of joint synovial in RA mice; the mechanism may be related
      to the regulation of Treg cells number in spleen and the expression of Foxp3,
      Galectin-9, RORgammat, CARMA1, NF-kappaB, mRNA and protein expression.

PMID- 29354979
TI  - [Effects of electroacupuncture preconditioning on cerebral infarct volume and
      contents of TNF-alpha, IL-10 in serum of rats after cerebral ischemia-reperfusion
      injury].
AB  - OBJECTIVE: To explore the effect of electroacupuncture(EA) preconditioning on
      cerebral infarct volume and the contents of TNF-alpha, IL-10 in serum of rats
      with cerebral ischemia-reperfusion injury. METHODS: Thirty-six rats were randomly
      divided into a sham operation group, a model group and an EA preconditioning
      group, 12 rats in each group, which were further divided into 12 h and 24 h after
      reperfusion subgroups, 6 rats in each one. EA was used before model establishment
      for 2 weeks in the EA preconditioning group. The model of cerebral ischemia
      reperfusion injury in rats was established with modified Longa suture method. 12
      h and 24 h after reperfusion, the degree of neurological deficit was assessed by
      the modified behavioral scoring scale; the cerebral infarct volume was measured
      by TTC method and the contents of TNF-alpha, IL-10 in serum were detected by
      ELISA method. RESULTS: Compared with the model group, the neurological severity
      scores in the EA preconditioning group significantly reduced 12 h and 24 h after
      reperfusion (both P<0.05), the cerebral infarct volume in the EA preconditioning
      group significantly reduced 12 h and 24 h after reperfusion (both P<0.05).
      Compared with the sham operation group, the serum TNF-alpha, IL-10 contents in
      the model group increased 12 h and 24 h after reperfusion (both P<0.05). Compared
      with the model group, the serum TNF-alpha content reduced, while the serum IL-10
      content increased in the EA preconditioning group 12 h after reperfusion (both
      P<0.05). Compared with the model group, the serum TNF-alpha, IL-10 contents
      reduced in the EA preconditioning group 24 h after reperfusion (both P<0.05).
      CONCLUSION: EA preconditioning can improve neurological deficit, reduce cerebral
      infarct volume after cerebral ischemia-reperfusion injury in rats. The mechanism
      may be related to the regulation of EA on the dynamic balance between pro
      inflammatory cytokine TNF-alpha and anti-inflammatory cytokine IL-10 in
      peripheral blood of cerebral ischemia-reperfusion injury in acute phase, thus
      alleviate acute cerebral ischemia-reperfusion inflammatory response.

PMID- 29354980
TI  - [Tinnitus caused by heart disease and healed from heart].
AB  - Tinnitus is recognized as a refractory disease, which is common in clinic, and
      always treated from the liver and kidney. We treat tinnitus mainly by heart based
      on syndrome differentiation. It often works well when the left cukou pulse is
      abnormal. Referring to ancient literature, we find that the heart is related to
      ears by meridians, and the kidney and heart govern ears. The normal function of
      heart and kidney means normal hearing. The heart secretes atrial natriuretic
      polypeptins (ANP), whose receptor is widely distributed in ears and can increase
      the cochlear blood flow. In this paper we explore the relationship between the
      heart and the ears so as to provide theories of treatment by heart for tinnitus.

PMID- 29354981
TI  - [Acupuncture-moxibustion syndrome differentiation based on differences between
      jing-jin diseases and zangfu diseases].
AB  - The clinical syndrome differentiation system of acupuncture-moxibustion was
      proposed in this paper, which should reflect the core of acupuncture theory and
      characteristics of treatment, and take syndrome differentiation of meridian as
      key component. In case of meridian syndrome differentiation guided by syndrome
      differentiation of eight principles, extra emphasis should be placed on the
      differences of jing-jin diseases and zangfu diseases. Differentiating location
      should be key in jing-jin diseases; the acupoints should be selected according to
      location, and appropriate technique should be applied according to symptoms.
      Zangfu diseases should based on syndrome differentiation of meridian and assisted
      by syndrome differentiation of zangfu; the key of zangfu diseases treatment was
      meridian-based acupoint selection, assisted by location-based acupoint selection;
      the emphasis should be placed on special acupoints, and reinforcing and reducing
      technique was selected according to cold-heat and deficiency-excess.

PMID- 29354982
TI  - [Discussion on the acupuncture and moxibustion thoughts of diagnosis and
      treatment for secondary dysmenorrhea of adenomyosis on the basis of disease
      location and pathogenesis].
AB  - To discuss the acupuncture and moxibustion thoughts of diagnosis and treatment
      for secondary dysmenorrhea of adenomyosis on the basis of disease location and
      pathogenesis. In clinic, we take the "principle, method, prescription, acupoint
      and technic" as the outline, paying attention to identify disease location and
      establishing the method of "promoting blood to remove stasis, regulating
      thoroughfare vessel and conception vessel" on the basis of the pathogenesis of
      "stasis obstructing uterus, disharmony of thoroughfare vessel and conception
      vessel". The prescription combines "dredging" with "conditioning", and the
      emphasis should be different in different periods. In menstrual period, we put
      emphasis on activating the circulation of qi and blood as well as clearing
      meridians to relieve pain and choose the acupoints on the spleen meridian of foot
      taiyin and experimental points, such as Diji (SP 8), Sanyinjiao (SP 6), Ciliao
      (BL 32), Shiqizhui (EX-B 8). In the intermenstrual period, we regulate the qi and
      blood of thoroughfare vessel and conception vessel, and the function of viscera.
      The acupoints for the disease root are mainly at spleen meridian of foot-taiyin
      and conception vessel, such as Sanyinjiao (SP 6), Guanyuan (CV 4), Zigong (EX-CA
      1), Zusanli (ST 36). And the reinforcing and reducing technic are applied
      accordingly.

PMID- 29354983
TI  - [Interpretation of acupuncture theory from acupuncture application].
AB  - The relationship between acupuncture theory and clinical practice is getting
      problematic with the development of acupuncture clinical practice. In the paper,
      in view of the theoretic study itself, the reasons and the approaches to the
      recognition are explored. The characteristics of acupuncture therapeutic methods
      include the site for application and the technique method in generally. Their
      theoretical construction is relatively limited in the system category of
      acupuncture. The sites of acupuncture application are various, including vessels,
      the muscle regions of meridians, the intersection of skin and muscle,
      corresponding points and others. All of those lead to the variety of acupuncture
      in compliance with the acupuncture technique methods. The nearby action of
      acupoint is also the basic function of acupuncture stimulation, which is much
      related with the variety of acupuncture. Hence, it is believed that the full
      dimensional recognition of acupoints and the relevant theories of meridians is
      the foundation to ensure their significance in clinical guidance and the
      theoretic supports in the innovative methods.

PMID- 29354984
TI  - [Electroacupuncture for post stroke cognitive impairment: a systematic review and
      Meta-analyses].
AB  - OBJECTIVE: To systematically evaluate the efficacy and safety of
      electroacupuncture (EA) for post stroke cognitive impairment (PSCI). METHODS: The
      randomized clinical trials (RCTs) regarding EA for PSCI published before October
      of 2016 were researched in China National Knowledge Infrastructure (CNKI),
      Chinese Biomedical Database (CBM), WanFang database, VIP medicine information
      system, PubMed and Cochrane Library. The literature screening and information
      extraction was conducted by two independent reviewers. The quality assessment was
      performed based on the guidance of the Cochrane Reviewers' Handbook, and Meta
      analyses was performed by using RevMan 5.3 software. RESULTS: Totally 14 RCTs
      were included, involving 896 PSCI patients. The results of Meta-analyses showed
      the EA group was superior to the control group in improving the MMSE [MD =1.78,
      95% CI (0.24, 3.32), P =0.02], the MoCA [MD=1.92, 95% CI (0.96, 2.88), P<0.000
      1], P300 latency [MD =-11.01, 95% CI (-18.91, -3.11), P =0.000 6], P300 amplitude
      [MD=1.56, 95% CI (1.14, 1.98), P<0.000 01], FMA score [MD =10.74, 95% CI (2.67,
      18.82), P =0.009] and the clinical effective rate [RR =1.37, 95% CI (0.98, 1.91),
      P =0.06]. However, the comparison of BI score in both group had no significant
      differences [MD =6.38, 95% CI (-2.41, 15.18), P =0.15]. CONCLUSION: This Meta
      analyses confirmed EA is effective and safe for PSCI, which could improve
      cognitive function and motor function. However, because of low quality of the
      included studies, more well-designed multicenter RCTs are needed.

PMID- 29354985
TI  - [Exploration and construction of the full-text database of acupuncture literature
      in the Republic of China].
AB  - The ALIPORC full-text database is targeted at a specific full-text database of
      acupuncture literature in the Republic of China. Starting in 2015, till now, the
      database has been getting completed, focusing on books relevant with acupuncture,
      articles and advertising documents, accomplished or published in the Republic of
      China. The construction of this database aims to achieve the source sharing of
      acupuncture medical literature in the Republic of China through the retrieval
      approaches to diversity and accurate content presentation, contributes to the
      exchange of scholars, reduces the paper damage caused by paging and simplify the
      retrieval of the rare literature. The writers have made the explanation of the
      database in light of sources, characteristics and current situation of
      construction; and have discussed on improving the efficiency and integrity of the
      database and deepening the development of acupuncture literature in the Republic
      of China.

PMID- 29354986
TI  - [Mechanism of neural plasticity of acupuncture on chronic migraine].
AB  - Chronic migraine is one of neurological disorders with high rate of disability,
      but sufficient attention has not been paid in this field. A large number of
      clinical studies have shown traditional Chinese acupuncture is a kind of
      effective treatment with less side effects. Through the analysis of literature
      regarding acupuncture and migraine published from 1981 to 2017 in CNKI and PubMed
      databases, the mechanism of neural plasticity of acupuncture on chronic migraine
      was explored. It was believed the progress of chronic migraine involved the
      changes of neural plasticity in neural structure and function, and the neural
      plasticity related with neural sensitization during the process of chronic
      migraine was discussed from three aspects of electrophysiology, molecular
      chemistry and radiography. Acupuncture could treat and prevent chronic migraine
      via the mechanism of neural plasticity, but there was no related literature,
      hindering the further spreading and development of acupuncture for chronic
      migraine.

PMID- 29354987
TI  - [Clinical trial of gastroesophageal reflux disease with the disharmony between
      liver and stomach syndrome treated with acupuncture regulating qi based on the
      compatibility of the five meridians].
AB  - OBJECTIVE: To observe the clinical effects of the acupuncture regulating qi based
      on the compatibility of the five meridians and common western medication for
      gastroesophageal reflux disease with the disharmony between liver and stomach.
      METHODS: Sixty patients were divided into two groups according to non-erosive
      reflux disease (NERD) and reflux esophagitis (RE). Those in the two groups were
      randomly assigned into an observation group and a control group. There were 57
      cases included (28 in the observation group with 2 dropping, 29 in the control
      group with 1 dropping). Based on the life care, patients in the observation group
      were treated with 30 min acupuncture regulating qi based on the compatibility of
      the five meridians at Zusanli (ST 36), Chongyang (ST 42), Weishu (BL 21),
      Zhongwan (CV 12), Xingjian (LR 2), Shaofu (HT 8), Dadun (LR 1), Taichong (LR 3),
      Ganshu (BL 18), Qimen (LR 14), Danzhong (CV 17), Zhongting (CV 16), three times a
      week. Patients in the control group were treated with rabeprazole orally. All the
      treatment was given for consecutive 8 weeks. The clinical symptom score was
      observed before and after treatment and 4 weeks after treatment. The effects were
      evaluated from 3 aspects, including the main symptoms, esophagitis improvement
      under gastroscope and total clinical symptoms. RESULTS: After treatment and at
      follow-up, the symptom scores decreased in the two groups compared with those
      before treatment (all P<0.05), with better improvement in the observation group
      at follow-up (P<0.05). The symptom scores after treatment of the two types in the
      two groups decreased compared with those before treatment (all P<0.05). The total
      effective rate of heartburn after treatment in the observation group was 82.1%
      (23/28), which was lower than 93.1% (27/29) of the control group (P<0.05). The
      total effective rate of belching after treatment in the observation group was
      94.1% (16/17), which was better than 75.0% (15/20) in the control group (P<0.05).
      The total effective rate of the esophagitis improvement under gastroscope after
      treatment in the observation group was 75.0% (12/16), and that in the control
      group was 82.4% (14/17), without statistical significance (P>0.05). The total
      effective rate of the clinical symptoms after treatment in the observation group
      was 82.1% (23/28), and that in the control group was 86.2% (25/29), without
      statistical significance (P>0.05). CONCLUSION: Acupuncture regulating qi based on
      compatibility of the five meridians can effectively improve clinical symptoms and
      inflammation under gastroscope for gastroesophageal reflux disease with the
      disharmony between liver and stomach. This treatment has a longer curative effect
      and a greater alleviation of belching.

PMID- 29354988
TI  - [Effect of transcutaneous electrical acupoint stimulation on gastric emptying in
      patients undergoing surgery].
AB  - OBJECTIVE: To observe the effects of transcutaneous electrical acupoint
      stimulation (TEAS) on gastric emptying in patients undergoing selective surgery
      based on velocity of gastric emptying by ultrasonography. METHODS: A total of 75
      patients with selective operation of subarachnoid block at lower limb in the
      afternoon were randomly assigned to a TEAS group, a sham group and a control
      group, 25 patients in each one. All the patients were provided with semi-fluid
      diet at 8 a.m. The TEAS group was treated with TEAS 5 min after semi-fluid diets
      at bilateral Zusanli (ST 36) and Neiguan (PC 6) for 30 min, with frequency of 5
      Hz and intensity which was 1 mA lower than the tolerance threshold. The sham
      group patients were stimulated at the same acupoints with current intensity which
      was 1 mA lower than the sensory threshold. The control group received no
      treatment. On the day of operation, and ultrasonography was given at time of
      empty stomach (T0), immediately after the semi-fluid diets (T1), and every 30 min
      after diets (T2-T6), respectively, to measure the gastric content and emptying
      time at semire-clining position and right lateral position. RESULTS: The volume
      of gastric content in the three groups at T3-T6 was significantly less than that
      at T1 (all P<0.05). The volume of gastric content at T4-T6 at semire-clining
      position in the TEAS group was significantly less than that in the control group
      and sham group (all P<0.05). The volume of gastric content at T5-T6 at right
      lateral position in the TEAS group was significantly less than that in the
      control group and sham group (all P<0.05). The gastric emptying time in the TEAS
      group was significantly less than that in the control group and sham group (both
      P<0.05). CONCLUSION: The gastric emptying velocity could be evaluated by
      ultrasonography. TEAS could improve the velocity of gastric emptying and reduce
      the gastric emptying time.

PMID- 29354989
TI  - [Clinical effect of abdominal acupuncture for diarrhea irritable bowel syndrome].
AB  - OBJECTIVE: To compare the efficacy differences between abdominal acupuncture and
      western medication for diarrhea irritable bowel syndrome (IBS-D). METHODS: Sixty
      one patients with IBS-D were randomly assigned into an acupuncture group (30
      cases after 1 dropping) and a western medication group (28 cases after 2
      dropping). Acupuncture was used at Yinqiguiyuan points [Zhongwan (CV 12), Xiawan
      (CV 10), Qihai (CV 6), Guanyuan (CV 4)], Fusiguan points [bilateral Huaroumen (ST
      24), Wailing (ST 26)], Tiaopiqi point [bilateral Daheng (SP 15)], once every
      other day, 3 times a week. Pinaverium bromide tablet was used orally in the
      western medication group, 50 mg a time, 3 times a day. All the treatment was
      given for 4 weeks in the two groups. IBS symptom severity score (IBS-SSS) and
      clinical symptom scores for abdominal pain and distension, diarrhea, poor stool
      output, defecation urgency and stool abnormality were observed before and after
      the treatment as well as 3 months after treatment. Adverse reactions were
      recorded and the effects were evaluated. RESULTS: 1After treatment and at follow
      up, the IBS-SSS scores of the two groups were lower than those before treatment
      (all P<0.01). Compared with the western medication group, the scores and the
      improvements between the two time points and before treatment were better in the
      acupuncture group (P<0.05, P<0.01). 2The symptom scores in the two groups after
      treatment were lower than those before treatment including abdominal pain,
      abdominal distension, diarrhea, poor stool output, defecation urgency and stool
      abnormality (P<0.05, P<0.01), and the scores of abdominal pain, abdominal
      distension, diarrhea, poor stool output and stool abnormality in the acupuncture
      group were lower than those in the western medication group (P<0.05, P<0.01).
      3The total effective rate and the cured and remarkable effective rate of the
      acupuncture group were higher than those of the western medication group [(86.7%
      (26/30) vs 64.3% (18/28), P<0.05; 70.0% (21/30) vs 35.7% (10/28), P<0.01)], and
      the therapeutic efficacy of the acupuncture group was better than that of the
      western medication group (P<0.05). There was no adverse reaction. CONCLUSION:
      Abdominal acupuncture is more effective for IBS-D than western medication and can
      relieve abdominal pain, abdominal distension, diarrhea, poor stool output, stool
      abnormality, with long-term effect.

PMID- 29354990
TI  - [Spasmodic hemiplegia after stroke treated with scalp acupuncture, music therapy
      and rehabilitation: a randomized controlled trial].
AB  - OBJECTIVE: To evaluate the differences in the clinical therapeutic effects on
      spasmodic hemiplegia after stroke among the alliance therapy of scalp
      acupuncture, music therapy combined with rehabilitation, the simple
      rehabilitation therapy and the combination of music therapy and rehabilitation.
      METHODS: A total of 76 patients of post-stroke spasmodic hemiplegia were
      randomized into a rehabilitation group (25 cases), a combination group with music
      therapy and rehabilitation (25 cases) and an alliance therapy group with scalp
      acupuncture, music therapy and rehabilitation (26 cases). In the rehabilitation
      group, the routine rehabilitation therapy was applied, including the removal of
      various incentives that cause spasm, the correction of body position and the
      physical therapy. In the combination group, the music therapy was added on the
      basis of the treatment as the rehabilitation group. The music physician used the
      rhythmic auditory stimulation, the patterned sensory enhancement and the
      therapeutic instrumental music playing to set up the task in the treatment. In
      the alliance therapy group, scalp acupuncture was added on the basis of the
      treatment as the combination group. The anterior oblique line of vertex-tempora
      (MS 6) and the posterior oblique line of vertex-tempora (MS 7) on the
      contralateral side were selected and stimulated with penetrating needling
      technique. The needles were retained. During the needling retaining, the needles
      were rotated once every 10 min, for 2 min each time. The treatment was given one
      session a day, totally for 5 sessions a week, continuously for 4 weeks. The Fugl
      Meyer assessment (FMA), Barthel index (BI) and the modified Ashworth scale (MAS)
      of the affected elbow and the passive knee movement at static condition were
      observed in the patients before and after treatment. RESULTS: The results of FMA,
      BI and MAS were not different before treatment in the patients among the three
      groups (all P>0.05), indicating the comparability among groups. After treatment,
      FMA and BI scores were all increased apparently in the three groups as compared
      with those before treatment (all P<0.05). MAS grade was reduced remarkably as
      compared with that before treatment (all P<0.05). After treatment, FMA and BI
      scores in the alliance therapy group were higher than those in the combination
      group and the rehabilitation group (all P<0.05). FMA and BI scores in the
      combination group were higher than those in the rehabilitation group (both
      P<0.05). MAS grade in the alliance therapy group was lower than those in the
      combination group and the rehabilitation group (both P<0.05). MAS grade in the
      combination group was lower than that in the rehabilitation group (P<0.05).
      CONCLUSION: The alliance therapy with scalp acupuncture, music therapy and
      rehabilitation achieve the remarkable clinical therapeutic effects on post-stroke
      spasmodic hemiplegia as compared with the routine rehabilitation and the
      combination of music therapy and rehabilitation.

PMID- 29354991
TI  - [Chronic fatigue syndrome treated with transcutaneous electrical acupoint
      stimulation: a randomized controlled trial].
AB  - OBJECTIVE: To evaluate the clinical therapeutic effects and safety of chronic
      fatigue syndrome treated with transcutaneous electrical acupoint stimulation
      (TEAS) on the conception vessel and the governor vessel. METHODS: Eighty-nine
      patients of chronic fatigue syndrome were randomized into an observation group
      (46 cases) and a control group (43 cases). In the observation group, TEAS was
      applied at Dazhui (GV 14) and Mingmen (GV 4), Shenque (CV 8) and Guanyuan (CV 4)
      [the current intensity: (14+/-2) mA]. In the control group, the simulated TEAS
      was applied at the same acupoints as the observation group (the current
      intensity: 1 mA). The treatment was given for 30 min, once a day, 5 times a week
      and the treatment of 4 weeks was as 1 session in the two groups. One session of
      treatment was required. Before treatment and at the end of 1 session of
      treatment, the fatigue severity scale (FSS) was adopted to evaluate the fatigue
      symptoms and the somatic and psychological health report (SPHERE) was adopted to
      evaluate the potential symptoms and observe the safety of TEAS therapy. RESULTS:
      At the end of treatment, FSS score and SPHERE score in the control group were not
      different significantly as compared with those before treatment (both P>0.05).
      FSS score and SPHERE score in the observation group were reduced significantly as
      compared with those before treatment (both P<0.01). FSS score and SPHERE score in
      the observation group were reduced apparently as compared with those in the
      control group (both P<0.001). In the entire process of treatment with TEAS, no
      any adverse reaction occurred. CONCLUSION: TEAS on the conception vessel and the
      governor vessel relieves fatigue symptoms and the potential symptoms in the
      patients of chronic fatigue syndrome. It is a safe therapy.

PMID- 29354992
TI  - [Moxibustion at Geshu (BL 17) for diabetic limb arterial obliteration at early
      stage].
AB  - OBJECTIVE: To compare the efficacy differences between moxibustion at Geshu (BL
      17) and oral administration of cilostazol on diabetic limb arterial obliteration
      (DLAO) at early stage as well as the impacts on hemorheology and arterial inner
      dimension of lower extremity. METHODS: Seventy patients of DLAO at early stage
      were randomly divided into an observation group and a control group, 35 cases in
      each one. The two groups were treated with regular treatment of blood glucose and
      blood lipid. The patients in the control group was treated with oral
      administration of cilostazol, 50 mg, twice a day; the patients in the observation
      group were treated with moxibustion at Geshu (BL 17), once a day. The consecution
      treatment of two weeks constituted one session, and totally 4 sessions were
      given. The total syndrome score, hemorheology index (including low and high shear
      viscosity of blood, plasma viscosity, hematocrit and erythrocyte aggregation
      index) and arterial inner dimension of lower extremity (including popliteal
      artery, posterior tibial artery and dorsalis pedis artery) were compared before
      and after treatment. RESULTS: Compared with those before treatment, the total
      syndrome score, hemorheology index and arterial inner dimension of lower
      extremity were significantly improved after treatment in the two groups (all
      P<0.05). The total syndrome score, hemorheology index in the observation group
      were superior to those in the control group (all P<0.05), but the improvement of
      arterial inner dimension of lower extremity was not significantly different
      between the two groups (P>0.05). After treatment, the total effective rate was
      91.4% (32/35) in the observation group, which was significantly superior to 85.7%
      (30/35) in the control group (P<0.05). CONCLUSION: Moxibustion at Geshu (BL 17)
      is superior to oral administration of cilostazol for DLAO at early stage, which
      could effectively improve the clinical symptoms, blood flow and blood vessel and
      increase the blood flow of lower limb.

PMID- 29354993
TI  - [Effect of joss stick moxibustion combined with pricking and cupping for acute
      herpes zoster and its mechanism of analgesia].
AB  - OBJECTIVE: To observe the effects of conventional western medication and joss
      stick moxibustion combined with pricking and cupping for herpes zoster in acute
      stage, and to explore its analgesic mechanism. METHODS: Seventy patients with
      acute herpes zoster were randomized into an observation group (33 cases after 2
      dropping) and a control group (34 cases after 1 dropping). Patients in the
      observation group were treated with joss stick moxibustion combined with pricking
      and cupping at local ashi points for 7 times, once every other day. Oral
      acyclovir, vitamin B1 and mecobalamin tablets were applied in the control group
      for continuous 14 days, and interferon injection was used for continuous 6 days,
      etc. The herpes evaluation indexes of blister stopping time, scab time and
      decrustation time as well as pain intensity were observed before and after
      treatment. Peripheral serum substance P (SP) content of herpes local situation
      was detected. The comprehensive effects were evaluated. RESULTS: The blister
      stopping time, scab time and decrustation time in the observation group were
      shorter than those in the control group (all P<0.05). There was no statistical
      significance for pain relief degree between the two groups (P>0.05). The pain
      beginning to ease time and duration time in the observation group were better
      than those in the control group (both P<0.05). The contents of SP in the two
      groups decreased after treatment (both P<0.01), and it was better in the
      observation group (P<0.05). The total effective rate of the observation group
      after treatment was 87.9% (29/33), and that of the control group was 85.3%
      (29/34), which were not statistically significant (P>0.05). The cured rate of the
      observation group was better than that of the control group [66.7% (22/33) vs
      58.8% (20/34), P<0.05]. CONCLUSION: Joss stick moxibustion combined with pricking
      and cupping are effective for herpes zoster, which have quicker and good
      analgesic effects than conventional western medication. Its mechanism may be
      related to reducing the content of SP more fast and to a larger degree.

PMID- 29354994
TI  - [Early age-related macular degeneration treated with emayaoling acupuncture
      technique: a randomized controlled trial].
AB  - OBJECTIVE: To compare the differences in the clinical therapeutic effects on
      early age-related macular degeneration (AMD) in the treatment between emayaoling
      acupuncture technique and regular acupuncture. METHODS: A total of 110 patients
      of AMD were randomized into an observation group (55 cases, 73 eyes) and a
      control group (55 cases, 76 eyes). In the observation group, acupuncture was
      applied at Cuanzhu (BL 2) and Yiming (EX-HN 14). The needles were retained for 30
      min. Additionally, Ganshu (BL 18), Pishu (BL 20) and Shenshu (BL 23) were
      stimulated with quick needling technique. Emayaoling needling technique was
      applied. The needle was rotated with the thumb and index finger of the puncture
      hand, forward and backward. The strong and large amplitude were given when the
      thumb moved forward, and while, the week and small amplitude required when moving
      backward. The gentle movement was required in the entire procedure. In the
      control group, the point selection was same as the observation group. The points
      were stimulated with regular technique. The needle retaining time was same as the
      observation group. The treatment was given once every two days in the two groups
      and for 3 months continuously. The visit was followed up for 3 months. Before and
      after treatment, as well as at follow-up, the eyesight, the effect on macular
      area and the macular retinal structure [the macular nerve fiber layer (MNFL),
      retinal neurepithelium layer (RNL), pigment epithelium and choroid capillary
      composite lay (PECCL)] were evaluated separately. RESULTS: 1. After treatment and
      at follow-up, the eyesight was improved as compared with that before treatment in
      the two groups, indicating the significant difference (both P<0.05). The
      differences in comparison before and after treatment, and in comparison of the
      follow-up with that before treatment, were improved in a larger amplitude in the
      observation group as compared with the control group, indicating the significant
      difference (both P<0.05). 2. Regarding the therapeutic effects on macular area,
      after treatment and at follow-up, the total effective rates were 83.6% (61/73)
      and 86.3% (63/73) in the observation group and were 63.2% (48/76) and 67.1%
      (51/76) in the control group separately. The results in the observation group
      were higher than those in the control group, indicating the significant
      difference between the two groups (both P<0.05). 3. Regarding the macular retinal
      structure, after treatment and at follow-up, the levels of MNFL, RNL and PECCL
      were all reduced as compared with those before treatment, indicating the
      significant difference (all P<0.05). After treatment and at follow-up, the levels
      of MNFL, RNL and PECCL in the observation group were all lower than those in the
      control group, indicating the significant difference (all P<0.05). CONCLUSION:
      The emayaoling acupuncture technique achieves better clinical therapeutic effects
      on treatment of early AMD as compared with the regular acupuncture.

PMID- 29354995
TI  - [Correlation between eight extra meridians and viscera].
AB  - Correlation between meridians and viscera is the core of meridian theory, and
      eight extra meridians are a vital part of meridian system. Based on the running
      courses, diseases and modern researches of eight extra meridians, we found that
      governor and heel vessels were closely related to brain and kidney; conception
      and thoroughfare vessels were related to kidney and uterus; there was no defined
      relationship between link, belt vessels and viscera. The theory of eight extra
      meridians belonging to liver and kidney, and the clinical application of the
      eight confluence points provide evidence for the correlation between the eight
      extra meridians and viscera. The correlation research can fill up current
      meridian-viscus correlation theory and provide its new research thought.

PMID- 29354996
TI  - [Analysis of specificity of Shenque (CV 8) based on vascular biology].
AB  - To analyze the structural specificity of Shenque (CV 8) in terms of vascular
      biology from the three aspects of structure, tissue and molecular anatomies. On
      structural anatomy Shenque (CV 8) possessed defined vascular structure and was
      the only acupoint directly affected vascular intima. The basis of the specific
      therapeutic effects was owing to its relation with vessel and abundant
      microcirculation. Endothelial cells and microvascular endothelial cells were the
      tissue basis of the starting of therapeutic specificity. Molecular anatomy
      involved in the functions of transient receptor potential vanilloid family (TRPV)
      pathway and neuronal peptide secretion of endothelial cells in the structural
      function of the point. The "restoring yang for collapse" effect of salt-partition
      moxibustion at Shenque (CV 8) was analyzed based on the local biological
      specificity of blood vessels. The mechanisms were concluded as effectively
      targeting the dysfunction of microvascular endothelial cells and acquiring the
      maximum quantity of moxibustion by repeated warm-heat stimulation. The vascular
      biological structural features of Shenque (CV 8) may contribute to direct
      therapeutic effects on endothelial cells by the point.

PMID- 29354997
TI  - [Effects of acupuncture combined with Rule granule on breast tissue, prolactin
      and receptor expression in rats with mammary gland hyperplasia].
AB  - OBJECTIVE: To observe the effects of acupuncture combined with Rule granule on
      breast tissue, prolactin(PRL) and prolactin receptor (PRLR) expression in rats
      with mammary gland hyperplasia (MGH), and to explore its action mechanism to
      provide reference for clinical treatment of MGH. METHODS: Fifty-five female SD
      rats were randomly divided into a blank group, a model group, an acupuncture
      group, a Rule granule group and a combination group. Except the blank group, the
      rats in the remaining groups were treated with combined stimulation of estrogenic
      and progestational hormone to establish MGH model. After model establishment, the
      rats in the acupuncture group were treated with acupuncture at Plan A of
      "Tianzong" (SI 11), "Ganshu" (BL 18), "Zusanli" (ST 36) and Plan B of "Wuyi" (ST
      15), "Hegu" (LI 4), "Danzhong" (CV 17). Each plan was selected for one
      acupuncture treatment, and two plans were used alternately. The rats in the Rule
      granule group were treated with oral administration of granule, 3 mL per times.
      The rats in the combination group were treated with the same Rule granule,
      followed by acupuncture, once a day. After consecutive 30-day treatment, blood
      sample was collected from abdominal aorta; ELISA method was applied to measure
      the contents of PRL; the HE slice of mammary gland was observed under light
      microscope; the SABC immunohistochemical method was applied to measure the
      positive expression of PRLR. RESULTS: The morphology of breast tissue in the
      model group was consistent with MGH. Compared with the blank group, the serum PRL
      and the expression of PRLR were increased significantly in the model group (both
      P<0.01). Compared with the model group, the hyperplasia of mammary gland in each
      treatment group was improved, and serum PRL and expression of PRLR were
      significantly reduced (P<0.05, P<0.01), which were more significant in the
      combination group (both P<0.05). CONCLUSION: Acupuncture, Rule granule and its
      combination could effectively treat MGH, which is likely to reduce the level of
      serum PRL and inhibit the binding of PRL to PRLR, as a result, the level of E2 is
      indirectly inhibited, and the hyperplastic mammary gland is recovered. Compared
      with acupuncture or Rule granule, the combination of both has better overall
      efficacy.

PMID- 29354998
TI  - [Effects of heat-sensitive moxibustion on HPA axis in rats with irritable bowel
      syndrome].
AB  - OBJECTIVE: To observe the effects of heat-sensitive moxibustion on corticotropin
      releasing hormone (CRH), adrenocorticotrophic hormone (ACTH) and corticosterone
      (CORT) in rats with irritable bowel syndrome (IBS), and to explore the possible
      mechanism of heat-sensitive moxibustion on IBS. METHODS: According to random
      number table, 56 SD male rats were randomly divided into a blank group (n=8), a
      model group (n=8), a moxibustion group (n=32), and a mifepristone group (RU-486
      group, n=8). The rats in the blank group were treated with normal feeding; the
      rats in the model group, RU-486 group and moxibustion group were treated with
      chronic non-predictable stimulation for 21 days to establish IBS model. After
      model establishment, the rats in the moxibustion group were treated with
      moxibustion at "Mingmen" (GV 4) for 40 min, once a day for 14 days; the tail
      temperature was recorded every 5 min; according to the change of tail
      temperature, the rats were divided into a heat-sensitive moxibustion group and a
      non-heat-sensitive moxibustion group, and 8 rats were randomly selected in the
      two groups. The rats in the RU-486 group were treated with gastric administration
      of RU-486 for 14 days, while the rats in the blank group, model group and
      moxibustion groups were treated with identical volume of 0.9% NaCl. The rat
      general condition, body mass, behavioristics, intestinal propulsive rate and
      visceral sensitivity were observed in each group; ELISA method was used to detect
      serum CRH, ACTH and CORT; optical microscope was applied to observe the
      morphological changes of colon. RESULTS: (1) After model establishment, rats were
      in rest state, fatigued, with withered hair and dim ear; the stool was dry or
      watery; the body mass were slowly increased; the number of crossed grid and
      standing frequency were significantly reduced; visceral sensitivity was increased
      and intestinal propulsion rate was decreased; no obvious inflammatory cell
      infiltration was observed under microscope. (2) After intervention, compared with
      the blank group, the body mass and visceral sensitivity in the RU-486 group were
      not significantly different (both P>0.05), but the intestinal propulsion rate was
      decreased significantly (P<0.01). Compared with the blank group, the body mass of
      heat-sensitive moxibustion group and non-heat-sensitive moxibustion group was
      lower (both P<0.01), but the visceral sensitivity and intestinal propulsion rate
      were similar (both P>0.05). Compared with the model group, the body mass and
      visceral sensitivity were improved in the RU-486 group (P<0.05, P<0.01), but the
      intestinal propulsion rate was similar (P>0.05). The body mass, visceral
      sensitivity and intestinal propulsion rate of the heat-sensitive moxibustion
      group and the non-heat-sensitive moxibustion group were superior to those of the
      model group (P<0.05, P<0.01), and the body mass and intestinal propulsion rate of
      heat-sensitive moxibustion group were superior to those of non-heat-sensitive
      moxibustion group (both P<0.05). (3) After intervention, compared with the blank
      group, the contents of CRH, ACTH and CORT in the model group were significantly
      increased (P<0.05, P<0.01). Compared with the model group, the contents of CRH,
      ACTH and CORT of the heat-sensitive moxibustion group were statistically reduced
      (P<0.05, P<0.01), and the contents of CRH and ACTH in the non-heat-sensitive
      moxibustion group were statistically reduced (P<0.05, P<0.01); the content of CRH
      in the RU-486 group was reduced (P<0.05), but the contents of ACTH and CORT were
      increased (P<0.05, P<0.01). Compared with the non-heat-sensitive moxibustion
      group, the heat-sensitive moxibustion group was better in the improvement of CRH
      (P<0.05), but there was no significant difference of ACTH and CORT between the
      two groups (both P>0.05). CONCLUSION: Heat-sensitive moxibustion could reduce the
      contents of CRH, ACTH and CORT through the HPA axis, and improve the function of
      gastrointestinal motility to treat IBS.

PMID- 29354999
TI  - [Origin and thought on the philosophical ideas of acupuncture in Chinese
      medicine].
AB  - Acupuncture in Chinese medicine has been a treasure in Chinese traditional
      medicine for thousands of years. It is opposite to many basic theories in modern
      medicine in dynasties. Different from the cross compatibility and interactions
      among medical medicines, acupuncture in Chinese medicine has its own
      consolidation and inherent philosophical ideas. In view of this, how to discuss
      the philosophical ideas and its development of acupuncture in Chinese medicine
      becomes of great importance. It is crucial to clearly answer the three
      theoretical propositions in the development of acupuncture in Chinese medicine.
      Firstly, the differences in acupuncture should be identified between the ancient
      time and the modern time. The issues focus on the origin of Huangdi Neijing
      (Yellow Emperor's Internal Medicine) and its philosophical divergence. Secondly,
      the origin of acupuncture should be identified, whether it is from China or
      India. Thirdly, the differences in acupuncture should be identified between China
      and the west, focusing on the explanation and rectification of the
      interrelationship between the acupuncture in Chinese medicine and the western
      acupuncture. Hence, the basic features are discussed on the reality of
      acupuncture in Chinese medicine as well as its diversity. Finally, the
      proposition is extended on how to holistically grasp the philosophical foundation
      of acupuncture in Chinese medicine and its future trend.

PMID- 29355000
TI  - [The current situation of acupuncture definition in international organizations
      and legislation of some countries].
AB  - Acupuncture is developing rapidly in the world, and more attention is paid on
      acupuncture in various countries. Because of the cultural differences, there are
      different views on acupuncture between China and the west, which has brought
      influence and challenge to the development of acupuncture in the world.
      Acupuncture-related research is becoming increasingly extensive and complex, but
      the definition of acupuncture is lack of unified standards. The definition of
      acupuncture is in urgent need. Based on the analysis of acupuncture definition in
      the 201 international organizations of 48 countries on five continents and
      legislation of representative countries, this paper summarized the development
      status of acupuncture in foreign countries, and put forward that the definition
      of acupuncture should adopt the model of small connotation and large extension,
      integrate discipline superiority, expand the scope of acupuncture, and focus on
      the overall situation.

PMID- 29355001
TI  - [Comments on the definition of "acupuncture science"].
AB  - The experts in China believe that the substance of "dry needling" is in the
      category of acupuncture therapy for the treatment by needle inserting the human
      body. But, its recognition has not been implied from the definition of
      "acupuncture science". Since 1970 s, the different definitions of it are closely
      related to TCM theories, due to which, it has been limited. This flaw restricts
      the development of acupuncture theory, narrows the connotation of acupuncture
      science and goes against the communication of traditional Chinese acupuncture
      theory. No matter regarding the theory or technique, the acupuncture therapy
      nowadays changes greatly in its connotation. Rather than guided by TCM theories,
      acupuncture therapy mainly includes the nerve trunk stimulation theory, the
      cerebral function orientation therapy, biological holographic therapy, fascia
      stimulation therapy and trigger therapy, etc. Expect that the medical devices
      used in these therapies are same as the traditional acupuncture, these methods
      cannot be regarded in the category of acupuncture science when the current
      definition of it is considered. Hence, the writer is trying to define
      "acupuncture science" as: acupuncture science refers to the science for the
      methodology and mechanism of therapeutic devices, e.g. acupuncture therapy and
      moxibustion therapy, for the prevention and treatment of disease by stimulating
      the body, and its theory includes but not limits in traditional Chinese medical
      theory.

PMID- 29355002
TI  - [Is acupuncture ineffective in treating infertility associated with polycystic
      ovary syndrome? A reanalysis of data on the clinical trial by WU Xiaoke's team
      published on JAMA].
AB  - WU Xiaoke, Stener-Victorin and Richard Legro's team published a randomized
      clinical trial entitled Effect of acupuncture and clomiphene in Chinese women
      with polycystic ovary syndrome: a randomized clinical trial in JAMA on June 27,
      2017. Their conclusion is "this finding does not support acupuncture as an
      infertility treatment in such women". We found that the trial design had serious
      flaws and that the results could not lead to the conclusion. Based on the
      reanalysis for the study data and those published in other medical journals
      recently from the team, it was found that acupuncture plus clomiphene or control
      acupuncture plus clomiphene had more excellent live birth rate, ovulation rate
      and cumulative ovulation rate than clomiphene alone, with statistical and
      clinical significance. The conclusion of the trial is potentially incorrect.

PMID- 29355003
TI  - [Some issues from Effect of acupuncture and clomiphene in Chinese women with
      polycystic ovary syndrome in JAMA].
AB  - In order to avoid international experts and scholars questioning the clinical
      effect of acupuncture, based on the traditional acupuncture theory and research
      reports, some questions are proposed from the research design, acupuncture effect
      and outcome explanation on the study of Effect of acupuncture and clomiphene in
      Chinese women with polycystic ovary syndrome published in JAMA in June 2017. And
      some thoughts and suggestions for the future development of the clinical
      acupuncture study are showed.

PMID- 29355004
TI  - [Exploration on the history of acupuncture in Chinese Buddhist Canon].
AB  - It is believed that acupuncture science of Buddhist medicine has a long history
      and great characteristics after the investigation, research and analysis on the
      historic literature of acupuncture in Chinese Buddhist Canon. The writers tried
      to give the statements from 4 aspects. 1. Science of acupuncture in the time of
      Buddha. Firstly, the Buddhist acupuncture was mentioned in the time of Buddha,
      including substantial acupuncture, finger acupuncture and mental acupuncture. The
      substantial acupuncture refers to metal needle, plant needle, stone needle, bone
      needle, etc. Finger acupuncture means taking finger as a needle. Mental
      acupuncture implies that the Buddhism idea is considered in acupuncture.
      Secondly, the Buddhist medicine is the combination of acupuncture and herbal
      medicine. The needle box had become the necessity of the medical scholars in
      traveling. 2. Achievements of medical Buddhists in dynasties. In the paper, 33
      medical Buddhists were listed, such as AN Shigao, YU Fakai, etc. They made the
      great contributions to the development of Buddhist medicine of acupuncture. 3.
      The characteristics of Buddhist acupuncture in clinical diagnosis and treatment.
      1) The combination of acupuncture and herbal medicine and this mutual
      supplementation; 2) Mutual treatment of acupuncture and psychological therapy; 3)
      Remarkable therapeutic effects of specific acupuncture techniques, such as Yan
      needling technique and acupotomy; 4) Medical cases of Buddhist acupuncture; and
      5) Precaution of misdiagnosis and prevention of mistreatment. 4. The penetrating
      statement of acupuncture techniques by the Buddhists in dynasties. 1) The cause
      effect theory is introduced in treatment and diagnosis by medical Buddhists. The
      effectiveness is achieved through causality system. 2) Cataract is treated with
      gold needle. 3) The medical master is not qualified if nothing to know on
      acupuncture. The authors believe that the substantial acupuncture techniques need
      to be further studied and the non-substantial one requests us to be perceived.

PMID- 29355005
TI  - [Application of gene chip technology for acupuncture research over the past 15
      years].
AB  - To explore the application of gene chip technology in the acupuncture research so
      as to provide evidences for the mechanism of acupuncture for regulating bodies.
      The literature on the application of gene chip technology in the acupuncture
      field from 2001 to 2016 was collected in PubMed, Springer, CNKI and WANFANG
      databases, which was analyzed and summarized. There were some achievements of the
      technology for acupuncture research, focusing on the five aspects, including the
      study of the relationship between meridian-point and viscera, the influencing
      factors of acupuncture effect, the effect and mechanism of acupuncture analgesia,
      the mechanism of acupuncture anti-aging, the effect and mechanism of acupuncture
      for diseases of each system. Gene chip technology plays an important role in
      researching acupuncture mechanism. It is an important technology for genomics
      study of acupuncture. However, there are also some disadvantages such as high
      cost, deficient data mining, non-uniform observation objects, deficient
      professionals, etc. All those need further resolution so as to promote the
      application of this technology in the acupuncture researching field.

PMID- 29355007
TI  - Potential Mechanisms for Enhanced Zika Epidemic and Disease.
AB  - A number of mechanisms have driven the explosive epidemics and severe diseases of
      Zika virus since 2007. Here, we comment on how herd immunity, heterologous
      flavivirus preimmunity, and viral mutations could enhance the epidemic potential
      and disease severity of Zika virus in humans.

PMID- 29355006
TI  - [Economic and Health impact of influenza vaccination with adjuvant MF59 in
      population over 64 years in Spain].
AB  - OBJECTIVE: Influenza is an important health problem due to the mortality it can
      cause directly or indirectly as well as the complications and the economic and
      social costs it produces. Influenza epidemics are being addressed through
      vaccination campaigns aimed at preventing cases and complications, and the
      vaccine is officially recommended, as in the case of Spain, for certain risk
      groups, such as older people, chronic diseases and institutionalized population.
      The adjuvanted influenza vaccine with MF59, indicated for population over 65
      years, has been shown to be more immunogenic than conventional influenza
      vaccines. The objective of this study is to assess the impact on the national and
      regional budget of the seasonal vaccination campaigns carried out in Spain using
      the MF59 adjuvanted vaccine compared to a conventional vaccine in a population
      older than 65 years. METHODS: We analyzed the budgetary impact of the use of the
      MF59-adjuvanted vaccine in the national territory and by Autonomous Communities
      through a modeling of two alternatives, conventional vaccination versus adjuvant
      vaccination with MF59 in a population older than 65 years. The cases of avoided
      influenza, avoided complications and avoided costs, as well as the economic
      impact of the vaccination program have been calculated. RESULTS: With the
      available information, the budgetary impact of using the influenza vaccine with
      MF59 in all the over 65 years, amounts to 6,967,288.10 ?, avoiding for the
      national set a cost of 89.5 million Euros, which represents a potential savings
      of 82 million Euros and a cost-benefit ratio of 12.83. CONCLUSIONS: The use of
      the influenza vaccine with the MF59 adjuvant to all those over 65 years would
      mean an increase in the efficiency of the vaccination programs currently proposed
      in all the Autonomous Communities and in the Spanish state.

PMID- 29355008
TI  - Sensitive Photodetection with Photomultiplication Effect in an Interfacial
      Eu2+/3+ Complex on a Mesoporous TiO2 Film.
AB  - A simple device structure composed of an interfacial Eu2+/3+ complex on a
      mesoporous TiO2 film is developed by a solution process and acts as the high
      performance photodetector with photomultiplication phenomena. The electron
      transfer from the photoexcited organic ligand, 2,2':6',2"-terpyridine (terpy), as
      a photosensitizer to TiO2 is accelerated by the reduction level of Eu3+/2+ ions
      chemically bonding among terpy and TiO2, resulting in the generation of a large
      photocurrent. It is worth noting that its external quantum efficiency is in
      excess of 105% under applied reverse bias. The corresponding responsivity of the
      device is also determined to be 464 A/W at an irradiation light intensity of 0.7
      mW/cm2 (365 nm), which is more than 3 orders of magnitude larger than those of
      inorganic photodetectors. A dark current of the device can be reduced to 10-9
      A/cm2 by introducing a Eu oxide thin-film layer as a carrier blocking layer at
      the interface between transparent conducting oxide (TCO) and the TiO2 layer, and
      the specific detectivity reaches 5.2 * 1015 jones at 365 nm with -3 V. The
      performance of our organic-inorganic hybrid photodetector surpasses those of
      existing ultraviolet photodetectors.

PMID- 29355009
TI  - Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for Decreasing
      Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its Anticancer
      Bioactivity Against Colorectal Cancer.
AB  - We have successfully demonstrated that the host-guest complex of carboxylated
      pillar[6]arene with oxaliplatin (OxPt) exhibits low cytotoxicity toward normal
      cells and displays higher anticancer bioactivity against colorectal cancer cells
      than OxPt itself. Owing to higher binding affinity of carboxylated pillar[6]arene
      with spermine (SPM) than that with OxPt, the encapsulated OxPt can be thoroughly
      released from its host-guest complex by the competitive replacement with SPM.
      This supramolecular chemotherapy works well both in vitro and in vivo for SPM
      overexpressed cancers, such as colorectal cancer. Compared to OxPt itself, the
      anticancer bioactivity of this host-guest complex is further improved by about
      20%. Such an improvement results from the combined effect of controlled release
      of OxPt from its host-guest complex and simultaneous consumption of SPM by
      carboxylated pillar[6]arene. It is anticipated that this supramolecular strategy
      may be extended to other clinical anticancer drugs for decreasing their severe
      side effects and improving their anticancer bioactivity, thus enriching the realm
      of supramolecular chemotherapy.

PMID- 29355010
TI  - Sustainable Radical Cascades to Synthesize Difluoroalkylated Pyrrolo[1,2
      a]indoles.
AB  - We disclose herein a photocatalytic difluoroalkylation and cyclization cascade
      reaction of N-(but-2-enoyl)indoles with broad substrate scopes in up to 90%
      isolated yield. This method provides sustainable and efficient access to
      synthesize difluoroalkylated pyrrolo[1,2-a]indoles with a quaternary carbon
      center under mild conditions.

PMID- 29355011
TI  - Inhibitors of Influenza A Virus Polymerase.
AB  - The propensity of influenza virus to develop resistance to commonly prescribed
      drugs highlights the need for continuing development of new therapeutics.
      Biological and structural investigations of the enzymatic and interaction domains
      among influenza A virus polymerase subunits have broadened the target reservoir
      for drug screening. With the wealth of knowledge from these studies,
      identification of small-molecule and peptidic inhibitors that specifically
      abrogate polymerase activity or disrupt the polymerase assembly has emerged as an
      innovative and promising approach. Importantly, those domains are highly
      conserved among influenza subtypes and thus minimize the emergence of drug
      resistant mutants. An overview of the reported enzymatic inhibitors and protein
      protein disruptors has been provided, in our effort to facilitate the development
      of next-generation anti-influenza therapeutics.

PMID- 29355012
TI  - Evaluation of Transport Parameters in MoS2/Graphene Junction Devices Fabricated
      by Chemical Vapor Deposition.
AB  - We demonstrated imaging of the depletion layer in a MoS2/graphene heterojunction
      fabricated by chemical vapor deposition and obtained their transport parameters
      such as diffusion length, lifetime, and mobility by using scanning photocurrent
      microscopy (SPCM). The device exhibited a n-type operation, which was determined
      by the MoS2 layer with a lower mobility. The SPCM revealed the presence of the
      depletion layer at the heterojunction, whereas graphene provided an excellent
      electrical contact for the MoS2 layer without resulting in a rectifying behavior,
      even if they were anchored within a very short range. The polarity of the
      photocurrent signal switched when we applied a drain-source bias voltage, from
      which we extracted the potential barrier at the junction. More importantly, a
      bias-dependent SPCM allowed us to simultaneously record the diffusion lengths of
      both majority and minority carriers for the respective MoS2 and graphene layers.
      By combining the diffusion lengths with the lifetimes measured by femtosecond
      SPCM, we determined the electron and hole mobilities in each layer, from which we
      found that the electron mobility (160 cm2 V-1 s-1) was higher than the hole
      mobility (80 cm2 V-1 s-1) in MoS2, whereas the hole mobility (15 000 cm2 V-1 s-1)
      was relatively higher in graphene.

PMID- 29355014
TI  - Smooth Interfacial Scavenging for Resistive Switching Oxide via the Formation of
      Highly Uniform Layers of Amorphous TaOx.
AB  - We demonstrate that the inclusion of a Ta interfacial layer is a remarkably
      effective strategy for forming interfacial oxygen defects at metal/oxide
      junctions. The insertion of an interfacial layer of a reactive metal, that is, a
      "scavenging" layer, has been recently proposed as a way to create a high
      concentration of oxygen defects at an interface in redox-based resistive
      switching devices, and growing interest has been given to the underlying
      mechanism. Through structural and chemical analyses of Pt/metal/SrTiO3/Pt
      structures, we reveal that the rate and amount of oxygen scavenging are not
      directly determined by the formation free energies in the oxidation reactions of
      the scavenging metal and unveil the important roles of oxygen diffusibility.
      Active oxygen scavenging and highly uniform oxidation via scavenging are revealed
      for a Ta interfacial layer with high oxygen diffusibility. In addition, the Ta
      scavenging layer is shown to exhibit a highly uniform structure and to form a
      very flat interface with SrTiO3, which are advantageous for the fabrication of a
      steep metal/oxide contact.

PMID- 29355013
TI  - Interaction between Ester-Type Tea Catechins and Neutrophil Gelatinase-Associated
      Lipocalin: Inhibitory Mechanism.
AB  - Tea is thought to alleviate neurotoxicity due to the antioxidative effect of
      ester-type tea catechins (ETC). Neutrophil gelatinase-associated lipocalin (NGAL)
      can sensitize beta-amyloid (Abeta) induced neurotoxicity, and inhibitors of NGAL
      may relieve associated symptoms. As such, the interactions of ETC with NGAL were
      investigated by fluorescence spectrometry and molecular simulation. NGAL
      fluorescence is quenched regularly when being added with six processing types of
      tea infusion (SPTT) and ETC. Thermodynamic analyses suggest that ETC with more
      catechol moieties has a stronger binding capacity with NGAL especially in the
      presence of Fe3+. (-)-Epicatechin 3-O-caffeoate (ECC), a natural product isolated
      from Zijuan green tea, shows the strongest binding ability with NGAL (Kd = 15.21
      +/- 8.68 nM in the presence of Fe3+). All ETC are effective in protecting nerve
      cells against H2O2 or Abeta1-42 induced injury. The inhibitory mechanism of ETC
      against NGAL supports its potential use in attenuation of neurotoxicity.

PMID- 29355015
TI  - Spatial Atmospheric Pressure Atomic Layer Deposition of Tin Oxide as an
      Impermeable Electron Extraction Layer for Perovskite Solar Cells with Enhanced
      Thermal Stability.
AB  - Despite the notable success of hybrid halide perovskite-based solar cells, their
      long-term stability is still a key-issue. Aside from optimizing the photoactive
      perovskite, the cell design states a powerful lever to improve stability under
      various stress conditions. Dedicated electrically conductive diffusion barriers
      inside the cell stack, that counteract the ingress of moisture and prevent the
      migration of corrosive halogen species, can substantially improve ambient and
      thermal stability. Although atomic layer deposition (ALD) is excellently suited
      to prepare such functional layers, ALD suffers from the requirement of vacuum and
      only allows for a very limited throughput. Here, we demonstrate for the first
      time spatial ALD-grown SnOx at atmospheric pressure as impermeable electron
      extraction layers for perovskite solar cells. We achieve optical transmittance
      and electrical conductivity similar to those in SnOx grown by conventional vacuum
      based ALD. A low deposition temperature of 80  degrees C and a high substrate
      speed of 2.4 m min-1 yield SnOx layers with a low water vapor transmission rate
      of ~10-4 gm-2 day-1 (at 60  degrees C/60% RH). Thereby, in perovskite solar
      cells, dense hybrid Al:ZnO/SnOx electron extraction layers are created that are
      the key for stable cell characteristics beyond 1000 h in ambient air and over
      3000 h at 60  degrees C. Most notably, our work of introducing spatial ALD at
      atmospheric pressure paves the way to the future roll-to-roll manufacturing of
      stable perovskite solar cells.

PMID- 29355016
TI  - Anisotropic Ion Diffusion and Electrochemically Driven Transport in
      Nanostructured Block Copolymer Electrolytes.
AB  - Nanostructured block copolymer electrolytes have the potential to enable solid
      state batteries with lithium metal anodes. We present complete continuum
      characterization of ion transport in a lamellar polystyrene-b-poly(ethylene
      oxide) copolymer/lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) electrolyte
      as a function of salt concentration. Electrochemical measurements are used to
      determine the Stefan-Maxwell salt diffusion coefficients [Formula: see text],
      [Formula: see text], and [Formula: see text]. Individual self-diffusion
      coefficients of the lithium- and TFSI-containing species were measured by pulsed
      field gradient NMR (PFG-NMR). The NMR data indicate that salt diffusion is
      locally anisotropic, and this enables determination of a diffusion coefficient
      parallel to the lamellae, D?, and a diffusion coefficient through defects in the
      lamellae, D?. We quantify anisotropic diffusion by defining an NMR morphology
      factor and demonstrate that it is correlated to defect density seen by
      transmission electron microscopy. We find agreement between the electrochemically
      determined Stefan-Maxwell diffusion coefficients and the diffusion coefficient D?
      determined by PFG-NMR. Our work indicates that the performance of nanostructured
      block copolymer electrolytes in batteries is strongly influenced by ion transport
      through defects.

PMID- 29355017
TI  - Redox-Responsive Core-Cross-Linked Block Copolymer Micelles for Overcoming
      Multidrug Resistance in Cancer Cells.
AB  - Success of chemotherapy as a treatment for cancer has been often inhibited by
      multidrug resistance (MDR) of the cancer cells. There is a clear need to generate
      strategies to overcome this resistance. In this work, we have developed redox
      responsive and core-cross-linked micellar nanocarriers using poly(ethylene
      glycol)-block-poly(2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate)
      diblock copolymers (PEG-b-PLAHEMA) with tunable swelling properties for the
      delivery of drugs toward drug-sensitive MDA-MB-231 and drug-resistant MDA-MB-231
      (231R) cancer cells. PEG-b-PLAHEMA containing varying number of 2
      (methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate (LAHEMA) units were
      synthesized by employing the reversible addition-fragmentation chain transfer
      polymerization technique. The block copolymer self-assembly, cross-linking
      induced by reduction, and de-cross-linking triggered time-dependent controlled
      swelling of micelles were studied using dynamic light scattering, fluorescence
      spectroscopy, and transmission electron microscopy. In vitro cytotoxicity,
      cellular uptake efficiency, and glutathione-responsive anticancer activity of
      doxorubicin (DOX) encapsulated in core-cross-linked block copolymer micelles
      (CCMs) toward both drug-sensitive and drug-resistant cancer cell lines were
      evaluated. Significant reduction in IC50 was observed by DOX-loaded CCMs toward
      drug-resistant 231R cancer cell lines, which was further improved by
      coencapsulating DOX and verapamil (a P-glycoprotein inhibitor) in CCMs. Thus,
      these reduction-sensitive biocompatible CCMs with tunable swelling property are
      very promising in overcoming MDR in cancer cells.

PMID- 29355018
TI  - Evidence of Tailoring the Interfacial Chemical Composition in Normal Structure
      Hybrid Organohalide Perovskites by a Self-Assembled Monolayer.
AB  - Current-voltage hysteresis is a major issue for normal architecture organo-halide
      perovskite solar cells. In this manuscript we reveal a several-angstrom thick
      methylammonium iodide-rich interface between the perovskite and the metal oxide.
      Surface functionalization via self-assembled monolayers allowed us to control the
      composition of the interface monolayer from Pb poor to Pb rich, which, in
      parallel, suppresses hysteresis in perovskite solar cells. The bulk of the
      perovskite films is not affected by the interface engineering and remains highly
      crystalline in the surface-normal direction over the whole film thickness. The
      subnanometer structural modifications of the buried interface were revealed by X
      ray reflectivity, which is most sensitive to monitor changes in the mass density
      of only several-angstrom thin interfacial layers as a function of substrate
      functionalization. From Kelvin probe force microscopy study on a solar cell cross
      section, we further demonstrate local variations of the potential on different
      electron-transporting layers within a solar cell. On the basis of these findings,
      we present a unifying model explaining hysteresis in perovskite solar cells,
      giving an insight into one crucial aspect of hysteresis for the first time and
      paving way for new strategies in the field of perovskite-based opto-electronic
      devices.

PMID- 29355019
TI  - Photoreaction Dynamics of LOV1 and LOV2 of Phototropin from Chlamydomonas
      reinhardtii.
AB  - Phototropin is a blue light sensor protein found in higher plants and green
      algae. Photochemical reactions of a variety of differently truncated constructs
      of a phototropin from Chlamydomonas reinhardtii (Cr) (LOV1, LOV1-hinge, LOV2,
      LOV2-linker, and hinge-LOV2) are investigated. In the dark state, LOV1 is in
      dynamic equilibrium between the monomer and dimer, and the main photochemical
      reaction is dimerization of the monomer and dissociation of the dimer. On the
      other hand, LOV1-hinge exists as the monomer and the photochemical reaction is
      the dimerization reaction associated with the unfolding of the helix of the hinge
      domain. LOV2 in the dark state is monomeric. The conformation changes after the
      photoexcitation of LOV2 and LOV2-linker are minor, which differs notably from the
      reaction of LOV2-Jalpha and LOV2-linker from Arabidopsis thaliana (At). The
      linker region, including the Jalpha helix, is rather stable upon photoexcitation.
      The helix of the hinge domain of hinge-LOV2 is slightly unfolded in the dark
      state, and the major photoreaction is the dimerization event. The dark recovery
      rate of LOV2 was found to decrease significantly in the presence of the hinge
      domain. These photochemical properties of Cr phot are considerably different from
      those of At phot regarding conformational changes and their kinetics, although Cr
      phot has been reported to rescue the phot function in At. The differences and the
      diversity of phots are discussed.

PMID- 29355020
TI  - In Situ Generation of Cyclopentadienol Intermediates from 2,4-Dienals.
      Application to the Synthesis of Spirooxindoles via a Domino Polycyclization.
AB  - An efficient domino polycyclization combining different classes of pericyclic
      reactions leads to complex spiroxindoles under mild conditions. This domino
      process represents a rare example of an in situ formation of cyclopentadienol
      derivatives from an interrupted iso-Nazarov electrocyclization of 2,4-dienals and
      their use in [4 + 2] cycloaddition reactions. According to the reaction
      conditions, different polycyclic architectures are obtained in good yields and
      excellent diastereoselectivities.

PMID- 29355021
TI  - Pd(0)-Catalyzed Intermolecular Dearomatizing [3 + 2] Spiroannulation of Phenol
      Based Biaryls and Allenes.
AB  - Readily available phenol-derived biaryls reacted with allenes under palladium
      catalysis to provide a variety of highly valuable spiro[cyclohexane-1,1'-indene]
      2,5-dien-4-ones. This new catalytic process, involving a key step of
      regioselective allylative dearomatization of phenol, proceeded efficiently
      through a [3 + 2] spiroannulation pathway by overcoming undesired beta-hydride
      elimination. Preliminary asymmetric studies showed that high enantioselectivity
      could be realized by using a commercially available PHOX ligand. Moreover, the
      potential application of this method was exemplified by several further
      transformations.

PMID- 29355022
TI  - Probing the Conformation of an IgG1 Monoclonal Antibody in Lyophilized Solids
      Using Solid-State Hydrogen-Deuterium Exchange with Mass Spectrometric Analysis
      (ssHDX-MS).
AB  - Therapeutic proteins are often formulated as lyophilized products to improve
      their stability and prolong shelf life. The stability of proteins in the solid
      state has been correlated with preservation of native higher order structure
      and/or molecular mobility in the solid matrix, with varying success. In the
      studies reported here, we used solid-state hydrogen-deuterium exchange with mass
      spectrometric analysis (ssHDX-MS) to study the conformation of an IgG1 monoclonal
      antibody (mAb) in lyophilized solids and related the extent of ssHDX to
      aggregation during storage in the solid phase. The results demonstrate that the
      extent of ssHDX correlated better with aggregation rate during storage than did
      solid-state Fourier-transform infrared (ssFTIR) spectroscopic measurements.
      Interestingly, adding histidine to sucrose at different formulation pH conditions
      decreased aggregation of the mAb, an effect that did not correlate with
      structural or conformational changes as measured by ssFTIR or ssHDX-MS. Moreover,
      peptide-level ssHDX-MS analysis in four selected formulations demonstrated global
      changes across the structure of the mAb when lyophilized with sucrose, trehalose,
      or mannitol, whereas site-specific changes were observed when lyophilized with
      histidine as the sole excipient.

PMID- 29355023
TI  - PSO-Assisted Development of New Transferable Coarse-Grained Water Models.
AB  - We have employed two-to-one mapping scheme to develop three coarse-grained (CG)
      water models, namely, 1-, 2-, and 3-site CG models. Here, for the first time,
      particle swarm optimization (PSO) and gradient descent methods were coupled to
      optimize the force-field parameters of the CG models to reproduce the density,
      self-diffusion coefficient, and dielectric constant of real water at 300 K. The
      CG MD simulations of these new models conducted with various timesteps, for
      different system sizes, and at a range of different temperatures are able to
      predict the density, self-diffusion coefficient, dielectric constant, surface
      tension, heat of vaporization, hydration free energy, and isothermal
      compressibility of real water with excellent accuracy. The 1-site model is ~3 and
      ~4.5 times computationally more efficient than 2- and 3-site models,
      respectively. To utilize the speed of 1-site model and electrostatic interactions
      offered by 2- and 3-site models, CG MD simulations of 1:1 combination of 1- and 2
      /3-site models were performed at 300 K. These mixture simulations could also
      predict the properties of real water with good accuracy. Two new CG models of
      benzene, consisting of beads with and without partial charges, were developed.
      All three water models showed good capacity to solvate these benzene models.

PMID- 29355024
TI  - The transition of adolescents with juvenile idiopathic arthritis or epilepsy from
      paediatric health-care services to adult health-care services: A scoping review
      of the literature and a synthesis of the evidence.
AB  - Young people with long-term health conditions (LTCs) can face challenges when
      making the transition to adult health services. This paper sought to identify
      studies that assess and explore transitional care for young people with LTCs. Two
      conditions were used as exemplars: juvenile idiopathic arthritis (JIA) and
      epilepsy. A scoping review of the literature was conducted by using search terms
      to search for papers in English between 2001 and 2016 concerning transitional
      care on four databases. Qualitative papers were reviewed and synthesized using
      thematic analysis. Quantitative papers using health outcomes were also
      synthesized. Twenty-eight papers were selected for review. Despite the wealth of
      literature concerning aspects of transitional care that are key to a successful
      transition for young people with JIA or epilepsy, there is a paucity of outcomes
      that define 'successful' transition and consequently a lack of reliable research
      evaluating the effectiveness of transitional care interventions to support young
      people moving to adult health services.

PMID- 29355025
TI  - Holding children for procedures: An international survey of health professionals.
AB  - Children undergoing clinical procedures can experience pain and/or anxiety. This
      may result in them being unwilling to cooperate and being held still by parents
      or health professionals. This study aimed to capture an international perspective
      of health professionals' reported practices of holding children still for
      clinical procedures. An online questionnaire was distributed through network
      sampling to health professionals working with children aged under 16 years of
      age. A total of 872 responses were obtained from Australia ( n = 477), New
      Zealand ( n = 237) and the United Kingdom ( n = 158). Responses were from nurses
      ( n = 651), doctors ( n = 159) and other professionals ( n = 53). Health
      professionals reported children as held still for clinical procedures quite often
      (48%) or very often (33%). Levels of holding varied significantly according to
      country of practice, profession, student status, length of time working within a
      clinical setting, training received and the availability of resources in the
      workplace. Health professionals who gained permissions (assent from children
      and/or consent from parents) before procedures were less likely to hold children
      still for a clinical procedure than those who did not. Holding children still for
      procedures is an international practice, which is influenced by training, access
      to guidance, country of practice and profession. Children's permission and
      parental consent is often not sought before a child is held for a procedure to be
      completed.

PMID- 29355026
TI  - Efficacy Outcomes of Endovascular Versus Surgical Revascularization in Critical
      Limb Ischemia: Results From a Prospective Cohort Study.
AB  - Data on efficacy outcomes of endovascular versus surgical revascularization in
      patients with critical limb ischemia (CLI) in contemporary practice are limited.
      In this prospective cohort study, 353 consecutive patients with CLI were enrolled
      and allocated to endovascular (PTA [percutaneous transluminal angioplasty]),
      surgical (SURG), or no revascularization (No REVASC) after interdisciplinary
      consensus. Outcome measures were sustained primary clinical success (sPCS;
      survival without major amputation, repeated target extremity revascularization,
      and freedom from CLI), limb salvage, and amputation-free survival. Propensity
      matched Kaplan-Meier analyses and stratified log-rank tests were performed. The
      PTA, SURG, and No REVASC groups consisted of 264, 62, and 27 patients,
      respectively. Compared to SURG patients, PTA patients were significantly older,
      had more risk factors, and more often had ischemic lesions. Propensity score
      adjusted analyses showed no significant differences: sPCS was 51.3%/52.2%, limb
      salvage rate 91.5%/93.7%, and major amputation-free survival 90.5%/87.2% at 12
      months for PTA and SURG, respectively. Amputation-free survival for the No REVASC
      group was 69% at 12 months. In conclusion, endovascular and surgical
      revascularization in CLI has comparable efficacy outcomes after 12 months.
      Contemporary overall outcome of patients with CLI is considerably better compared
      to earlier studies.

PMID- 29355027
TI  - Leisure-Time Physical Activity, Subjective Age, and Self-Rated Memory in Middle
      Aged and Older Adults.
AB  - Memory concerns are common in middle-aged and older adults. This study
      investigated the relation of leisure-time physical activity to self-rated memory
      and the possible mediating role of subjective age in this relationship in middle
      aged and older adults. Cross-sectional analyses were conducted with a sample of
      1,608 middle-aged and older adults from the second wave of the National Survey of
      Midlife Development in the United States (MIDUS2). In a path analysis conducted
      with Mplus, a higher level of leisure-time physical activity was associated with
      a more positive appraisal of memory compared to others of one's age; younger
      subjective age partially mediated this relationship. Neither gender nor age-group
      moderated the association. Age, race, education, marital status, health status,
      and negative affect were controlled for in the analyses. These findings suggest a
      possible role of physical activity in countering the effects of age stereotypes
      on perceived memory.

PMID- 29355028
TI  - Impact of change over time in self-reported discrimination on blood pressure:
      implications for inequities in cardiovascular risk for a multi-racial urban
      community.
AB  - OBJECTIVES: The 21st century has seen a rise in racism and xenophobia in the
      United States. Few studies have examined the health implications of heightened
      institutional and interpersonal racism. This study examines changes in reported
      discrimination and associations with blood pressure over time among non-Latino
      Blacks (NLBs), Latinos, and non-Latino Whites (NLWs) in an urban area, and
      variations by nativity among Latinos. DESIGN: Data from a probability sample of
      NLB, Latino, and NLW Detroit, Michigan residents were collected in 2002-2003,
      with follow-up at the same addresses in 2007-2008. Surveys were completed at 80%
      of eligible housing units in 2008 (n = 460). Of those, 219 participants were
      interviewed at both time points and were thus included in this analysis.
      Discrimination patterns across racial/ethnic groups and associations with blood
      pressure were examined using generalized estimating equations. RESULTS: From 2002
      to 2008, NLBs and Latinos reported heightened interpersonal and institutional
      discrimination, respectively, compared with NLWs. There were no differences in
      associations between interpersonal discrimination and blood pressure. Increased
      institutional discrimination was associated with stronger increases in systolic
      and diastolic blood pressure for NLBs than NLWs, with no differences between
      Latinos and NLWs. Latino immigrants experienced greater increases in blood
      pressure with increased interpersonal and institutional discrimination compared
      to US-born Latinos. CONCLUSIONS: Together, these findings suggest that NLBs and
      Latinos experienced heightened discrimination from 2002 to 2008, and that
      increases in institutional discrimination were more strongly associated with
      blood pressure elevation among NLBs and Latino immigrants compared to NLWs and US
      born Latinos, respectively. These findings suggest recent increases in
      discrimination experienced by NLBs and Latinos, and that these increases may
      exacerbate racial/ethnic health inequities.

PMID- 29355029
TI  - Utility of cardiac MRI in determining percutaneous versus surgical post
      infarction ventricular septal defect repair.
AB  - AIM: Postmyocardial infarction ventricular septal defect (VSD) is a rare
      complication that can lead to rapid hemodynamic patient decompensation. The type
      of VSD repair relies on several factors including: size, location, timing and
      surgical expertise. CASE: A 63-year-old man with a ST-elevation myocardial
      infarction underwent percutaneous coronary intervention of the right coronary
      artery. A holosystolic murmur was notable postcatheterization, and transthoracic
      echocardiogram confirmed a VSD. To characterize the VSD, a cardiac MRI
      demonstrated a large, serpiginous VSD and longitudinal septal tear. Given the
      anatomic complexity and stable hemodynamics, a surgical trans-left ventricular
      patch repair was performed. CONCLUSION: We emphasize the importance of cardiac
      magnetic resonance as a decision-making tool, utilizing imaging to ascertain the
      anatomy combined with hemodynamics to determine optimal individualized therapy.

PMID- 29355031
TI  - A new coumarin from stem bark of Calophyllum wallichianum.
AB  - A phytochemical study carried out on the plant, Calophyllum wallichianum has led
      to the isolation of a new coumarin, wallimarin T (1) and a known coumarin,
      calanolide E (2) along with two common triterpenes, friedelin (3) and
      stigmasterol (4). The structures of these compounds were elucidated with the aid
      of spectroscopic analyses such as FT-IR, GC-MS, and NMR. MIC assay against the
      Bacillus bacteria were conducted on the extracts and this gave MIC values ranging
      from 0.313 to 1.25 mg/mL. Compound 2 was weakly inhibitory towards the Bacilli
      strains with MIC values ranging from 0.25-0.50 mg/mL. Wallimarin T (1) was not
      active towards all four bacteria. Overall, the extracts exhibited weak
      bactericidal properties whereas compound 2 was not bactericidal on the tested
      bacteria. The hexane and chloroform extracts of the plant were found to be
      inhibitors to the growth of Bacillus megaterium, Bacillus cereus, Bacillus
      pumilus and Bacillus subtilis.

PMID- 29355032
TI  - A thoracic extradural chordoid meningioma: a unique case report and literature
      review.
AB  - We describe the unique case of a patient being diagnosed with a thoracic
      extradural chordoid meningioma following her presentation with mild lower limb
      pyramidal weakness and a T8 sensory level. This is the first report of an
      extradural chordoid meningioma being identified in the thoracic spine. The tumour
      was successfully resected through a posterior thoracic laminectomy approach. Post
      operatively, her neurological deficit resolved and to date she has not
      experienced a radiological recurrence. In this report, we review the literature
      and discuss this unusual tumour's characteristics and prognostic significance.

PMID- 29355030
TI  - Allosteric modulators of cannabinoid receptor 1: developing compounds for
      improved specificity.
AB  - The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is
      located primarily in the central nervous system. CB1 is a therapeutic target
      which may impact pathways to mediate pain, neurodegenerative disorders, hunger,
      and drug-seeking behavior. Despite these benefits, development of orthosteric
      therapeutic compounds, which target the endogenous ligand-binding site of CB1,
      has been challenging due to detrimental side effects including psychoactivity,
      depression, and suicidal thoughts. However, CB1 also has an allosteric binding
      site(s), which is topographically distinct from the orthosteric site. Allosteric
      modulation of CB1 has a number of potential advantages including providing a
      mechanism for more precise control of downstream pathways and circumventing these
      side effects. In this review, we summarize the concept of allosteric modulation
      and focus on the structure-activity relationship studies of the well
      characterized allosteric modulators, ORG27569 and PSNCBAM-1 and their
      derivatives, and a few other recent modulators. We review studies on the
      properties of these modulators on CB1 signaling in cells and their effects in
      vivo. While many current allosteric modulators also produce complex outcomes,
      they provide new advances for the design of CB1 centered therapeutics.

PMID- 29355033
TI  - The Impact of Operating Room Layout on Circulating Nurse's Work Patterns and Flow
      Disruptions: A Behavioral Mapping Study.
AB  - AIM: To assess how the adjacencies of functionally different areas within
      operating rooms (ORs) can influence the circulating nurse's (CN) workflow
      patterns and disruptions. BACKGROUND: The CN plays a significant role in
      promoting patient safety during surgical procedures by observing, monitoring, and
      managing potential threats at and around the surgical field. Their work requires
      constant movement to different parts of the OR to support team members. The
      layout of the OR and crowded and cluttered environment might impact the CN's
      workflow and cause disruptions during the surgery. METHOD: A convenience sample
      of 25 surgeries were video recorded and thematically coded for CN's activities,
      locations, and flow disruptions. The OR layout was categorized into transitional
      zones and functional zones (workstations, supply zones, support zones, and
      sterile areas around the surgical table). CN's activities were classified into
      patient-, equipment-, material-, and information-related activities. Flow
      disruptions included those related to environmental hazards and layout. RESULTS:
      The CN traveled through multiple zones during 91% of the activities. The CN's
      workstation acted as a main hub from which the CN made frequent trips to both
      sides of the surgical table, the foot of the OR table, supply zones, and support
      zones. Transitional zones accounted for 58.3% of all flow disruption that the CN
      was involved in whereas 28% occurred in areas surrounding the OR bed. CONCLUSION:
      The similarity of the movement and flow disruption patterns, despite variations
      in OR layout, highlighted the adjacencies required between major zones that CNs
      regularly visit. These optimum adjacencies should be considered while designing
      ORs such that they are more efficient and safer.

PMID- 29355034
TI  - Further spectral and chromatographic studies of ambergris.
AB  - Jetsam ambergris, found washed ashore on beaches, is an environmentally modified
      form of a natural product of Sperm whales which sometimes develops a pleasant
      odour. Odorous samples have proved valuable in perfumery. Identification of
      jetsam ambergris by analysis of organic-soluble extracts by Fourier transform
      infra-red spectroscopy (FTIR) and of derivatised samples by gas chromatography
      mass spectrometry (GC-MS) has already been shown. Here, we describe a different
      method, in which characteristic alkenic protons and carbon atoms of the major
      constituent ambrein, were identified in whole extracts using nuclear magnetic
      resonance spectroscopy (NMR). The advantages of employing NMR spectroscopy
      included rapidity, reduced losses of volatiles compared to GC-MS and detection of
      non-GC amenable constituents. However, the identities and quantities of co
      occurring individual components (e.g. steroids) could not easily be assigned in
      the unfractionated extracts by NMR spectroscopy, whereas they were by GC-MS, so
      an approach combining FTIR, GC-MS and NMR spectroscopic methods is advocated.

PMID- 29355036
TI  - Communication aid provision and use among children and adolescents developing
      aided communication: an international survey.
AB  - A fundamental requirement of a supportive language development for young children
      who need aided communication is that an aided communication system is made
      available and its use is supported. There is limited information about the age at
      which children are typically provided with a communication aid or about how aided
      communication is used in everyday situations. Using questionnaire-based interview
      data, this study investigated (a) the pattern of provision of communication aids
      to 84 children and adolescents, (b) parents' and professionals' evaluation of the
      quality of communication across contexts, and (c) availability and use of aided
      communication in these contexts. The age at which the participants received their
      first aided system varied considerably across the group; however, most were
      considerably older than the age at which children with typical development
      usually begin to speak. Parents and professionals rated most everyday situations
      as good communication situations but reported that the participants did not have
      their main form of expressive language available in many of these situations, or
      did not use it much. Parents rated their child's education in relation to aided
      language positively, but many professionals indicated that they had limited
      knowledge about the participant's use of aided communication outside of the
      school environment, or about the parents' attitudes. The study gives insights
      into the language learning situation of children and adolescents who develop
      aided communication.

PMID- 29355035
TI  - Simultaneous targeting therapy for lung metastasis and breast tumor by blocking
      the NF-kappaB signaling pathway using Celastrol-loaded micelles.
AB  - Metastasis is one of the major obstacles for successful therapy of breast tumor.
      To inhibit the metastasis and growth of breast tumor simultaneously, a Celastrol
      (Cela) loaded glucolipid-like conjugates (CSOSA/Cela) with alphavbeta3-ligand
      Tetraiodothyroacetic acid (TET) modification (TET-CSOSA/Cela) were established to
      block nuclear factor-kappa B (NF-kappaB) signaling pathway. The distribution of
      TET-CSOSA was remarkably increased in lung metastasis and primary tumor of 4T1
      tumor-bearing mice by means of alphavbeta3 receptor-mediated interaction. The
      results demonstrated that TET-CSOSA/Cela significantly suppressed Bcl-2
      activation of lung metastatic cells and reduced MMP-9 expression of 4T1 breast
      tumor cells by blocking NF-kappaB. The inhibitory rates of TET-CSOSA/Cela against
      lung metastasis and primary tumor were raised to 90.72 and 81.15%, compared to
      those of Celastrol (72.15 and 46.40%), respectively. All results demonstrated the
      alphavbeta3 receptor targeted TET-CSOSA/Cela micelles exhibited great potential
      in treating lung metastasis and primary tumor simultaneously via blocking NF
      kappaB signaling pathway.

PMID- 29355038
TI  - The future of type 1 cannabinoid receptor allosteric ligands.
AB  - Allosteric modulation of the type 1 cannabinoid receptor (CB1R) holds great
      therapeutic potential. This is because allosteric modulators do not possess
      intrinsic efficacy, but instead augment (positive allosteric modulation) or
      diminish (negative allosteric modulation) the receptor's response to endogenous
      ligand. Consequently, CB1R allosteric modulators have an effect ceiling which
      allows for the tempering of CB1R signaling without the desensitization,
      tolerance, dependence, and psychoactivity associated with orthosteric compounds.
      Pain, movement disorders, epilepsy, obesity are all potential therapeutic targets
      for CB1R allosteric modulation. Several challenges exist for the development of
      CB1R allosteric modulators, such as receptor subtype specificity, translation to
      in vivo systems, and mixed allosteric/agonist/inverse agonist activity. Despite
      these challenges, elucidation of crystal structures of CB1R and compound design
      based on structure-activity relationships will advance the field. In this review,
      we will cover recent progress for CB1R allosteric modulators and discuss the
      future promise of this research.

PMID- 29355037
TI  - Neoadjuvant and adjuvant treatment in high-risk prostate cancer.
AB  - INTRODUCTION: High-risk prostate cancer (HRPCa) represents a heterogeneous
      disease with potential risk for local and distant progression. In these patients,
      a multi-modal approach consisting of neoadjuvant and/or adjuvant systemic
      therapies has been proposed. The aim of this review is to summarize the emerging
      roles of neoadjuvant and adjuvant therapies in HRPCa patients. Areas covered:
      This review collects the most relevant phase III randomized controlled trials
      (RCTs) testing the effect of neoadjuvant and adjuvant systemic therapies in
      combination with radical prostatectomy (RP) or radiotherapy (RT) for HRPCa
      patients. Specifically, the review examines the benefit provided by androgen
      deprivation therapy (ADT), chemotherapy (CHT), and novel antiandrogen agents in
      this setting. A search of bibliographic databases for peer-reviewed literature
      was conducted. Expert commentary: Three decades of RCTs demonstrated that
      adjuvant ADT is fundamental in HRPCa treated with RT. Conversely, ADT and CHT did
      not improve the survival of HRPCa patients managed with RP. The recent
      introduction of novel antiandrogen agents combined with an appropriated selection
      of patients at risk of cancer progression, may ultimately extend the indication
      of neoadjuvant and adjuvant therapy in surgical- and radio-treated patients.

PMID- 29355039
TI  - Protective effects of 3beta-angeloyloxy-8beta, 10beta-dihydroxyeremophila-7(11)
      en-12, 8alpha-lactone on paraquat-induced oxidative injury in SH-SY5Y cells.
AB  - 3beta-Angeloyloxy-8beta,10beta-dihydroxyeremophila-7(11)-en-12,8alpha-lactone
      (FJ1) inhibited effectively paraquat (PQ)-induced injury in SH-SY5Y cells. In
      this way, FJ1 was shown to reverse the PQ-induced activation of caspase-9 and
      caspase-3, the increase in Bax/Bcl-2 ratio, and the release of cytochrome c. The
      mechanism was associated with a reduction of oxidative stress, including the
      decrease in the levels of ROS and MDA and maintaining the activity of SOD and
      GSH. Taken together, findings revealed that FJ1 had protective effects against PQ
      induced injury via attenuating the oxidative stress in SH-SY5Y cells, which
      suggested that FJ1 might be a candidate for further evaluation against
      neurodegeneration in Parkinson's disease.

PMID- 29355040
TI  - Depression and anxiety in patients with chronic heart failure.

PMID- 29355041
TI  - Solving the problem of dose optimization of children's medicines.

PMID- 29355042
TI  - One new indolocarbazole alkaloid from the Streptomyces sp. A22.
AB  - One new indolocarbazole alkaloid, 12-N-methyl-k252c, together with eight known
      indolocarbazoles were isolated from the rice solid fermentation of the marine
      derived Streptomyces sp. A22. Their structures were elucidated on the basis of
      spectroscopic methods (UV, IR, HRESITOF MS, 1D NMR and 2D NMR). All of these
      compounds were evaluated for bromodomain-containing protein 4 (BRD4) inhibitory
      activities and cytotoxic activity assay, respectively. Compounds 4 and 5 showed
      moderate cytotoxic activity with an IC50 value of 3.52 and 3.93 MUM,
      respectively. Additionally, compound 1 also was tested for enzyme inhibition
      activities of protein kinases and showed moderate activity with IC50 values of
      0.91-1.84 MUM.

PMID- 29355043
TI  - Combination of separation and spectroscopic analytical techniques: application to
      compositional analysis of a minor citrus species.
AB  - The composition of juice and essential oil of Citrus limetta Risso was
      investigated. Multidimensional and enantio-gas chromatography were used for the
      elucidation of the volatile profile and the assessment of enantiomeric
      distribution. Predominant compounds were linalyl acetate (13.06 g/100 g), beta
      pinene (6.79 g/100 g), myrcene (1.40 g/100 g) and sabinene (1.05 g/100 g).
      Through a beta-cyclodextrin column eight chiral pairs were separated, equally
      distributed between laevorotatory and dextrorotatory enantiomers. Liquid
      chromatography with triple quadrupole ESI-MS and PDA detection showed the
      presence of flavonoids and phenolic compounds (791.34 +/- 36.83 and 32.97 +/-
      1.92 mg L-1, respectively) in the juice. Sugars (i.e. glucose 202.23 +/- 26.81
      and fructose 146.73 +/- 3.17 mM, respectively), aminoacids (i.e. proline 29.40 +/
      3.78 and GABA 8.90 +/- 0.95 mM) and organic acids (i.e. citrate 4.68 +/- 0.81
      mM) were determined in juice by means of 1H NMR spectroscopy.

PMID- 29355044
TI  - Introduction to the special issue on aided language processes, development, and
      use: an international perspective.
AB  - This introduction to the Special Issue discusses current theoretical approaches
      to language development and their application to aided language development. It
      also discusses some conceptual issues and aspects of aided language development
      that are relevant for the articles, and gives a short overview of the articles.

PMID- 29355045
TI  - Cardio-oncology: an evolving hybrid subspecialty.

PMID- 29355046
TI  - Feasibility and Preliminary Efficacy of Tailored Yoga in Survivors of Head and
      Neck Cancer: A Pilot Study.
AB  - PURPOSE: Treatment for head and neck cancer (HNC) results in long-term toxicities
      and increased physical and psychosocial survivor burden. There are a limited
      number of treatments for these late effects. Yoga postures, breath work,
      relaxation, and meditation, may improve these late effects. The purpose of this
      study was to examine the feasibility of a tailored yoga program in HNC survivors
      and obtain preliminary efficacy data. METHODS: This was a randomized wait-list
      control study of yoga-naive HNC survivors who were >3 months post-cancer
      treatment. Baseline data were collected. Participants were randomized to either
      an 8-week hatha yoga intervention group or a wait-list group. Feasibility and
      efficacy data were collected. At 4 and 8 weeks, patients underwent a repeat
      assessment of health. Wait-list control group participants were offered the yoga
      program after data collection. Descriptive statistics evaluated feasibility.
      Mixed effects general linear models were used to generate estimates of the
      efficacy outcomes. RESULTS: Seventy-three individuals were screened and 40 were
      eligible. All eligible individuals consented and enrolled. Five of the
      intervention group discontinued early and none in the wait-list control group.
      Feasibility was affirmed as participants were recruited and retained in the
      study, there were no adverse events, fidelity to protocol was demonstrated, and
      satisfaction rates were high. Efficacy measures indicated potential benefit for
      shoulder range of motion ( d = 0.57-0.86, P < .05), pain ( d = 0.67-0.90, P <=
      .005), and anxiety ( d = 0.59, P = .015). CONCLUSION: A tailored hatha yoga
      program is feasible and potentially efficacious for HNC survivors. Preliminary
      data supports further investigation of yoga in this population is needed.

PMID- 29355047
TI  - Type 1 long QT syndrome and psychological stress in a laboratory setting.
AB  - Trait-like sensitivity to stress in long QT syndrome patients has been documented
      previously. In addition, mental stress has been associated with symptomatic
      status of long QT syndrome. We examined whether the symptomatic type 1 long QT
      syndrome patients would be more sensitive to mental stress compared to
      asymptomatic patients and whether there would be differences in task-related
      physiological stress reactions between type 1 long QT syndrome patients and
      healthy individuals. The study population consisted of 21 symptomatic and 23
      asymptomatic molecularly defined KCNQ1 mutation carriers, their 32 non-carrier
      relatives and 46 non-related healthy controls, with mean ages of 37, 39, 35 and
      23 years, respectively. Electrocardiography was utilised to calculate inter-beat
      interval and high frequency and low frequency heart rate variability. Blood
      pressure was measured and mean arterial pressure and pulse pressure were
      calculated. Stress was induced using three different tasks: mental arithmetic,
      reaction time and public speech. Stress responses of symptomatic and asymptomatic
      type 1 long QT syndrome patients were not statistically different in any of the
      stress tasks. Short-term physiological stress reactivity of symptomatic type 1
      long QT syndrome patients appears to be normal and does not enhance the risk
      assessment of asymptomatic mutation carriers.

PMID- 29355049
TI  - Applying the Common Sense Model to predicting quality of life in alopecia areata:
      The role of illness perceptions and coping strategies.
AB  - Applying the Common Sense Model, this cross-sectional study examines associations
      between illness perceptions and quality of life and the mediating role of coping
      in 243 adults with alopecia areata, a chronic dermatological condition. At least
      some QoL impairment was reported by 84 percent of participants, with 31 percent
      reporting very to extremely large impairment. Stronger perceptions of
      consequences, emotional representations, identity, and lower attribution to
      chance were related to more impairment, with avoidant coping acting as (partial)
      mediator. Illness perceptions and avoidant coping seem to play an important role
      in QoL and are relevant intervention targets in alopecia areata.

PMID- 29355048
TI  - Making meaning of cancer: A qualitative analysis of oral-digestive cancer
      survivors' reflections.
AB  - This qualitative study aimed to confirm and extend research on meaning making
      after cancer. In all, 119 adults aged 41 to 88 years ( M = 65.50 years and
      standard deviation = 9.16 years) were interviewed 12 months after diagnosis of
      oral-digestive cancers. About half tried to understand why they got cancer (43%)
      and said that cancer changed their view of life (53%). Most (75%) reported that
      previous life experiences helped them cope with cancer. Cancer survivors made
      meanings in the areas of existential, social, and personal domains with both
      positive and negative content. Practitioners may wish to examine meaning making
      in these areas for those in distress after cancer.

PMID- 29355050
TI  - Big Five personality and health in adults with and without cancer.
AB  - Personality is associated with health, but examinations in patients with
      illnesses are lacking. We aimed to determine whether personality-physical health
      associations differed between community and cancer samples. This cross-sectional
      study involved 168 participants without cancer, 212 men with prostate cancer, and
      55 women with breast cancer. We examined whether the Big Five personality
      dimensions were associated with health behaviors and multiple health indicators.
      Higher conscientiousness and lower neuroticism were associated with better health
      behaviors and health ( rmax = .31), with few differences between community and
      cancer samples. Findings call for research on the implications of personality in
      patients with serious illnesses.

PMID- 29355051
TI  - Fraction From Lycium barbarum Polysaccharides Reduces Immunotoxicity and Enhances
      Antitumor Activity of Doxorubicin in Mice.
AB  - The aim of the present study was to investigate whether fraction from Lycium
      barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor
      activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated
      LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this
      study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor
      free mice were used and treated with either normal saline, Dox, or Dox plus LBP3.
      To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing
      mice were used and treated with either normal saline, Dox, LBP3, or Dox plus
      LBP3. The results showed that LBP3 did not protect against the body weight loss
      caused by Dox, but it promoted the recovery of body weight starting at day 5
      after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood
      lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and
      restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor
      bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral
      blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our
      results demonstrated that LBP3 could reduce the immunotoxicity and enhance
      antitumor activity of Dox.

PMID- 29355052
TI  - Injectable calcium phosphate scaffold with iron oxide nanoparticles to enhance
      osteogenesis via dental pulp stem cells.
AB  - Literature search revealed no systematic report on iron oxide nanoparticle
      incorporating calcium phosphate cement scaffolds (IONP-CPC). The objectives of
      this study were to: (1) use gammaFe2O3 nanoparticles (gammaIONPs) and alphaFe2O3
      nanoparticles (alphaIONPs) to develop novel IONP-CPC scaffolds, and (2)
      investigate human dental pulp stem cells (hDPSCs) seeding on IONP-CPC for bone
      tissue engineering for the first time. IONP-CPC scaffolds were fabricated.
      Physiochemical properties of IONP-CPC scaffolds were characterized. hDPSC seeding
      on scaffolds, cell proliferation, osteogenic differentiation and bone matrix
      mineral synthesis by cells were measured. Our data demonstrated that the
      osteogenic differentiation of hDPSCs was markedly enhanced via IONP incorporation
      into CPC. Substantial increases (about three folds) in ALP activity and
      osteogenic gene expressions were achieved over those without IONPs. Bone matrix
      mineral synthesis by the cells was increased by two- to three folds over that
      without IONPs. The enhanced cellular osteogenesis was attributed to: (1) the
      surface nanotopography of IONP-CPC scaffold, and (2) the cell internalization of
      IONPs released from IONP-CPC scaffold. Our results demonstrate that the novel CPC
      functionalized with IONPs is promising to promote osteoinduction and bone
      regeneration. In conclusion, it is highly promising to incorporate gammaIONPs and
      alphaIONPs into CPC scaffold for bone tissue engineering, yielding substantially
      better stem cell attachment, spreading and osteogenic differentiation, and much
      greater bone mineral synthesis by the seeded cells. Therefore, novel CPC
      scaffolds containing gammaIONPs and alphaIONPs are promising for dental,
      craniofacial and orthopaedic applications to substantially enhance bone
      regeneration.

PMID- 29355053
TI  - Harpagoside-induced anaphylactic reaction in an IgE-independent manner both in
      vitro and in vivo.
AB  - BACKGROUND: Harpagoside (HAR) is an active component of Scrophularia ningpoensis
      (SN), which has anti-inflammatory and anti-immune effects. SN is used widely in
      China to treat various diseases. Recently, SN has been used as a traditional
      Chinese medicine injection and used clinically. However, allergic responses to
      these injections are frequently reported. AIM: We examined whether the main
      component of SN, HAR, is associated with the allergic reaction to SN. METHODS:
      This study assessed the effects of HAR in mice and mast cell activation to
      characterize its anaphylactic effects and underlying mechanisms. Mice hindpaw
      swelling, serum allergy factor detection, enzyme-linked immunosorbent assays, and
      degranulation assays were performed to measure allergic mediators both in vivo
      and in vitro. RESULTS: The present study indicated that HAR induced paw swelling,
      interleukin-6, inositol triphosphate, tumor necrosis factor-alpha, and histamine
      increases in mice. Our in vitro data also showed that HAR induced beta
      hexosaminidase, inositol triphosphate, and interleukin-6 release, leading to mast
      cell degranulation. In contrast, neither C48/80 nor HAR induced local anaphylaxis
      in STOCK KitW-sh/HNihrJaeBsmJNju mice. CONCLUSIONS: HAR is a potential
      sensitization compound in SN, and these results provide information for the safe
      clinical use of SN.

PMID- 29355055
TI  - Recruiting ENT and Audiology patients into pharmaceutical trials: evaluating the
      multi-centre experience in the UK and USA.
AB  - OBJECTIVE: Recruiting into clinical trials on time and on target is a major
      challenge and yet often goes unreported. This study evaluated the adjustment to
      procedures, recruitment and screening methods in two multi-centre pharmaceutical
      randomised controlled trials (RCTs) for hearing-related problems in adults.
      DESIGN: Recruitment monitoring and subsequent adjustment of various study
      procedures (e.g. eligibility criteria, increasing recruiting sites and
      recruitment methods) are reported. Participants were recruited through eight
      overarching methods: trial registration, posters/flyers, print publications,
      Internet, social media, radio, databases and referrals. The efficiency of the
      recruitment was measured by determining the number of people: (1) eligible for
      screening as a percentage of those who underwent telephone pre-screening and (2)
      randomised as a percentage of those screened. STUDY SAMPLE: A total of 584
      participants completed the pre-screening steps, 491 screened and 169 participants
      were randomised. RESULTS: Both RCTs completed adjustments to the participant
      eligibility, added new study sites and additional recruitment methods. No single
      recruitment method was efficient enough to serve as the only route to enrolment.
      CONCLUSION: A diverse portfolio of methods, continuous monitoring, mitigation
      strategy and adequate resourcing were essential for achieving our recruitment
      goals.

PMID- 29355056
TI  - Anti-inflammatory effects of trans-cinnamaldehyde on lipopolysaccharide
      stimulated macrophage activation via MAPKs pathway regulation.
AB  - OBJECTIVES: Inflammation is a primary response of the innate immune system
      against various infections. Macrophages are a type of immune cell that have a
      critical role in the inflammation. Recent studies reported that various natural
      compounds could regulate immune responses such as inflammation. Trans
      cinnamaldehyde (TCA) is a natural compound from cinnamon, especially abundant in
      cinnamon bark. Previous studies reported that TCA has anti-biofilm, anti
      microbial, and anti-cancer activities. However, the anti-inflammatory effects and
      the mechanism of TCA on macrophages are still unknown. MATERIALS AND METHODS: Raw
      264.7 murine macrophage cells were used in this study. Major assays were MTT,
      Griess assay, Western blot, enzyme-linked immunosorbent assay (ELISA) and reverse
      transcription (RT)-PCR analysis. RESULTS: In this study, we investigated the anti
      inflammatory effects of TCA on the RAW 264.7 murine macrophage cell line. TCA
      significantly decreased lipopolysaccharide (LPS)-induced nitric oxide (NO)
      production in a dose-dependent manner. Moreover, TCA treatment significantly
      reduced mRNA expression and protein expression of inducible NO synthase (iNOS) in
      LPS-stimulated macrophages in a dose-dependent manner. TCA treatment also
      diminished the mRNA expression level and secretion of IL-1beta, IL-6 and TNF
      alpha in LPS-activated macrophages. TCA elicited the anti-inflammatory effects by
      inhibiting ERK, JNK and p38 MPAKs phosphorylation in the cells. DISCUSSION AND
      CONCLUSION: TCA elicits the anti-inflammatory effects on LPS-stimulated
      macrophage activation via suppression of MAPKs phosphorylation, and pro
      inflammatory gene expression. Therefore, this study provides important
      information regarding the use of TCA as a candidate therapeutic agent against
      inflammation.

PMID- 29355057
TI  - Comparison of laser ablation using multidirectional and forward-firing fibers in
      breast cancer.
AB  - BACKGROUND: The aim of this study was to compare the therapeutic effect of laser
      ablation using the forward-firing fiber and the multidirectional-firing fiber for
      breast cancer treatment with pathologic results. MATERIAL AND METHODS: An ex vivo
      study of laser ablation was conducted using normal breast and breast cancer
      tissue. Each ablated area was demarcated into three zones, and the temperature
      was measured. Laser ablations using multidirectional and forward-firing types of
      fiber were compared regarding the shape, diameter and aspect ratio of the ablated
      lesions. RESULTS: The ablated lesions were classified into three zones: a
      carbonized zone with complete tissue loss; a coagulated zone with no viable
      cells; and a non-damaged zone. The shape of the ablated lesion was elliptical
      using the forward-firing fiber and round using the multidirectional-firing fiber.
      Compared with normal breast tissue, breast cancer tissue required a more powerful
      setting for laser ablation to achieve necrosis, and the aspect ratio of the
      thermal lesion was higher for laser ablation using the multidirectional-firing
      fiber. CONCLUSIONS: The experimental results on breast tissue have shown that
      multidirectional-firing fiber is more effective than using forward-firing fibers
      and that this may prove to be another feasible therapeutic option for management
      of breast cancer.

PMID- 29355058
TI  - The relative predictive value of undergraduate versus graduate selection tools in
      two Australian medical schools.
AB  - CONTEXT: Monash University and the University of Western Australia admit both
      school-leavers and graduates into their Bachelor of Medicine and Bachelor of
      Surgery (MBBS) courses. The Undergraduate Medicine and Health Sciences Admission
      Test (UMAT) and the Graduate Medical Schools Admissions Test (GAMSAT) are used
      for selection, along with an academic score and an interview score. The aim of
      this study was to compare the relative predictive validity of the selected
      components in the two entry streams, particularly UMAT versus GAMSAT. METHODS:
      Aggregated scores for course outcomes were calculated in the categories of
      knowledge, clinical and total scores, at four-time points. A path analysis was
      conducted based on multivariate regressions with model constraint parameters
      defined across the outcome variables to investigate change over time. RESULTS:
      Academic scores were the strongest predictors of knowledge scores and end of
      course results. Interview scores had a small positive increasing effect, being
      stronger for clinical than knowledge outcomes. The effect size for GAMSAT was
      greater than for UMAT. CONCLUSIONS: Aptitude tests and interview scores added
      small but significant incremental predictive value to previous academic
      achievement. GAMSAT showed larger predictive value on outcomes than UMAT, for
      which one section (UMAT 3) had a negative effect.

PMID- 29355059
TI  - The choice of stimulation strategy affects the ability to detect pure tone inter
      aural time differences in children with early bilateral cochlear implantation.
AB  - OBJECTIVES: To investigate if the interaural time difference (ITD) ability is
      dependent of stimulation strategy. To examine the correlation between ITD,
      interaural level differences (ILD) and the ability to localize different sounds.
      METHODS: Thirty subjects aged 8-13 who were implanted bilaterally before 3 years
      of age were tested. Twenty of the subjects used processors programmed with fine
      structure (FS) strategy on both sides. ITD and ILD just noticeable difference
      (JND) of a 250 Hz pure tone was measured using their clinical processors.
      Furthermore, their ability to localize sound in the horizontal plane was measured
      using eye tracking. RESULTS: Ten of the 20 subjects with FS obtained an ITD
      threshold compared to none in the group without FS (0/10). ILD JND was correlated
      to localization ability of the broadband (BB) sound. Mean absolute error of the
      localization of a low-frequency (LF) sound was larger than that of a BB sound.
      CONCLUSIONS: The ability to detect ITD was present only when the cochlear implant
      stimulation had FS. The LF sound was more difficult to localize than the BB sound
      and ITD ability of FS strategies did not affect the localization ability of
      either sound. A low ILD seems necessary to improve the localization ability.

PMID- 29355060
TI  - Investigating superiority of novel bilosomes over niosomes in the transdermal
      delivery of diacerein: in vitro characterization, ex vivo permeation and in vivo
      skin deposition study.
AB  - Skin is considered the most accessible organ of the body because of its
      underlying capillary network. However, stratum corneum (SC), the upper most layer
      of skin, represents major diffusional barrier for most drugs. Hence, the use of
      edge activators (EAs) in designing novel elastic vesicles is hypothesized to
      impart their lipid bilayer with ultra-flexibility to trespass SC by high self
      optimizing deformability. To confirm this hypothesis, this work aimed at
      developing novel bilosomes by modulating conventional niosomal composition using
      different bile salts as EAs and investigating their superiority over niosomes for
      transdermal delivery of diacerein (DCN), as model drug. Bilosomes were prepared
      by thin film hydration (TFH) technique according to full 31.22 factorial design
      to select the optimal formulation using Design-Expert(r) software. The optimal
      bilosomes (B6) showed nanosized vesicles (301.65 +/- 17.32 nm) and 100.00 +/-
      0.00 % entrapment efficiency. Ex vivo permeation studies and in vivo evaluation
      revealed that B6 exhibited superior permeation and drug retention capacity
      compared to the conventional niosomal formulation and drug suspension.
      Furthermore, B6 was subjected to in vivo histopathological study using male
      Wistar rats which ensured its safety for topical application. Overall, the
      results confirmed the hypothesized superiority of bilosomes over niosomes for
      enhancing DCN flux across the skin.

PMID- 29355061
TI  - The impact of maternal body mass index on external cephalic version success.
AB  - OBJECTIVE: The purpose of this study is to determine the association between body
      mass index (BMI) and success of ECV. METHODS: This is a cross-sectional analysis
      of singleton live births in the USA from 2010 to 2014 using birth certificate
      data. Patients were assigned a BMI category according to standard WHO
      classification. Comparisons of success of ECV between the BMI categories were
      made using chi-square analysis with normal BMI as the reference group. Cochran
      Armitage test was performed to look for a trend of decreasing success of ECV as
      BMI increased. The odds for successful ECV were estimated using multivariate
      logistic regression analysis, adjusting for possible confounders. RESULTS: A
      total of 51,002 patients with documented ECV were available for analysis. There
      was a decreased success rate for ECV as BMI increased (p < .01). Women with a BMI
      of 40 kg/m2 or greater had a 58.5% success rate of ECV; women with a normal BMI
      had 65.0% success rate of ECV. Multivariate analyses demonstrated significant
      decrease in success of ECV in women with BMI of 40 kg/m2 or greater (OR 0.621, CI
      0.542-0.712). Among women with BMI of 40 kg/m2 or greater with successful ECV,
      59.5% delivered vaginally. In contrast, 81.0% of women with normal BMI and
      successful ECV delivered vaginally. CONCLUSIONS: Morbidly obese women have
      decreased success rate of ECV as BMI increases and decreased vaginal delivery
      rates after successful ECV.

PMID- 29355062
TI  - Effects of gestational and pregestational diabetes mellitus on the foetal heart:
      a cross-sectional study.
AB  - We examined the foetal cardiac structural and functional characteristics in
      diabetic pregnancies versus non-diabetic, healthy pregnancies. Between August
      2015 and April 2016, 32 pregnant women with pregestational diabetes, 36 pregnant
      women with gestational diabetes, and 42 healthy pregnant women were scheduled to
      have foetal echocardiograms to assess cardiac structure and function. In the
      diabetic groups, the foetal interventricular septum (IVS) thickness was
      significantly greater than in non-diabetics (p < .05) but none had an IVS >2 SD
      from normal. The peak velocity of tricuspid E, and the E/A ratio were
      significantly lower in the diabetic groups (p < .05). Tricuspid valve Ea values
      and the Ea/Aa ratio were lower in the diabetic group than in the control group (p
      < .05) but there was no significant difference between the pre-GDM and GDM groups
      (p > .05). Interventricular septal hypertrophy is the most common structural
      abnormality in diabetic pregnancies. These changes do not pose a risk to the
      foetal unless they cause functional impairment. Thus, we believe that it is
      important for diabetic pregnant women to be monitored for foetal cardiac
      diastolic dysfunction. Impact statement What is already known on this subject?
      Pregestational insulin-dependent diabetes mellitus is a relatively common
      condition in pregnancy, affecting up to 0.5% of the pregnant population. Foetuses
      of diabetic mothers are at an increased risk of perinatal morbidity and death.
      Gestational diabetes mellitus is under-recognised and affects up to 4% of
      pregnancies. Although diabetes mellitus is known to increase the risk of
      cardiovascular defects and structural changes (myocardial hypertrophy and
      diastolic dysfunction) due to foetal hyperglycaemia and hyperinsulinism, similar
      data in women with gestational diabetes is scarce. Moreover, the effect of
      maternal hyperglycaemia on foetal cardiac structure and function is unclear
      because of discordant results from previous studies. What do the results of this
      study add? In this study, we have used foetal echocardiography, two-dimensional
      US, pulsed wave Doppler and TDI to characterise the foetal cardiac structure and
      function in normal pregnancies as well as in the pregnancies complicated by GDM,
      and pregestational DM. Interventricular septum thickness is increased in women
      with pregestational diabetes mellitus and impaired diastolic function. The
      dominant right ventricle of the foetal circulation was affected earlier than the
      left ventricle. What are the implications of these findings for clinical practice
      and/or further research? Large population-based studies are required to establish
      the absolute risk of congenital heart defects in patients with pregestational
      diabetes and pregestational diabetes in the utility of routine screening.

PMID- 29355063
TI  - Using traditional or flipped classrooms to teach "Geriatrics and Gerontology"?
      Investigating the impact of active learning on medical students' competences.
AB  - BACKGROUND: The present study aims to investigate the effect of two educational
      strategies to teach geriatrics (flipped classroom-FL and traditional lectures-TR)
      in relation to a control group (no intervention) on students' competences.
      METHOD: An intervention study was conducted during the third year of medicine.
      Two different educational strategies (flipped classroom and traditional lectures)
      were incorporated into a theoretical-practical discipline of geriatrics. Students
      were evaluated about their attitudes towards older persons (Maxwell-Sullivan,
      UCLA geriatric attitudes), empathy (Maxwell-Sullivan), knowledge (Palmore and
      cognitive knowledge), skills (standardized patient assessment), and satisfaction
      with the activities. RESULTS: A total of 243 students were assessed. The FL group
      demonstrated greater gains in knowledge among students and improved attitude
      compared to the TR. We found no differences in the skills using a standardized
      patient. In addition, students exposed to FL felt more prepared to treat older
      people, believed they had more knowledge, were more satisfied, and evaluated the
      discipline's format better in relation to the traditional group. CONCLUSIONS:
      Strategies in teaching geriatrics can impact students' knowledge, attitudes, and
      satisfaction with the course. We found that the way this teaching is delivered
      can influence students' learning, since there were differences between active and
      traditional strategies.

PMID- 29355064
TI  - How learners learn: A new microanalytic assessment method to mapdecision-making.
AB  - BACKGROUND: Microanalytic techniques have shown considerable potential as avenues
      for understanding learning in a range of learning contexts. If a microanalytic
      approach is to be tested for utility, a suitable learning context is required. We
      chose problem-based learning (PBL) tutorials as our context. AIMS: We sought to
      determine if a new microanalytic approach is suitable for investigating the
      learning decisions made by students during PBL and what this form of
      microanalysis reveals. METHODS: Stimulated recall interviews were used to
      question 17 first year graduate-entry medical students regarding the conscious
      decisions behind their actions during one PBL case. Responses were categorized
      and used to construct process maps to illustrate the students' decision-making.
      These maps and the decisions within them were analyzed focusing on how learners
      learn. RESULTS: Stimulated recall interviewing (SRI) was conducted, during which
      students could articulate the conscious decisions they made during PBL. The data
      collected were used to construct 191 process maps and 802 categorized decisions
      for analysis. Students' decisions became increasingly self-centered as the case
      progressed while maintaining an awareness of group dynamics. CONCLUSIONS: The
      microanalytic approach employed in this study is a suitable tool for
      understanding the nature of learning in this, and other environments.

PMID- 29355065
TI  - Effect of combination of vitamin E and umbilical cord-derived mesenchymal stem
      cells on inflammation in mice with acute kidney injury.
AB  - BACKGROUND: The objective of this study is to investigate the effect of
      combination of umbilical cord-derived mesenchymal stem cell (UC-MSC) and vitamin
      E (VitE) on inflammation in mice with acute kidney injury (AKI). METHODS: UC-MSCs
      were isolated from pregnant wistar mice and cultured. A total of 90 female wistar
      mice were randomly divided into control group, AKI group, AKI + VitE group, AKI +
      UC-MSC group, and AKI + VitE + UC-MSC group (18 mice in each group) which were
      given no treatment, normal saline, VitE, UC-MSC, and VitE + UC-MSC, respectively.
      The renal pedicles on both sides were clipped for 50 min with micro-artery clips
      to induce AKI. Six mice were sacrificed at days 1, 3, and 7, while blood and
      kidney tissues were collected to detect levels of blood urea nitrogen (BUN) and
      creatinine (Scr). Kidney tissues were stained by HE staining to observe
      pathological changes; levels of interleukin-lbeta, TNF-alpha, interleukin-10, and
      beta-FGF were measured by ELISA. RESULTS: Compared with the control group, AKI
      mice showed higher levels of serum BUN and Scr, tubular swelling and necrosis
      suggesting that AKI model was successfully established. Mice in AKI + VitE group,
      AKI + UC-MSC group, and AKI + VitE + UC-MSC presented better renal function than
      mice of AKI group. Mice from AKI + VitE + UC-MSC group showed the best renal
      function with the least renal tubular injury (p < .05). ELISA detection revealed
      that pro-inflammatory cytokines were significantly increased and anti
      inflammatory cytokine levels were significantly decreased in all time points (p <
      .05). VitE, UC-MSC, and VitE + UC-MSC resulted in the increase of anti
      inflammatory cytokine levels and reduction of pro-inflammatory cytokine levels
      and the combination of VitE and UC-MSC performed favorable effect in the
      suppression of inflammation in AKI mice (p < .05). CONCLUSIONS: Combination of UC
      MSC and VitE significantly inhibited inflammatory reaction in kidney through the
      regulation of inflammatory cytokines in the microenvironment of kidney with AKI.
      Combination of UC-MSC and VitE presented therapeutic effect on AKI than the
      single use of UC-MSC or VitE.

PMID- 29355066
TI  - Circadian- and Light-driven Metabolic Rhythms in Drosophila melanogaster.
AB  - Complex interactions of environmental cues and transcriptional clocks drive
      rhythmicity in organismal physiology. Light directly affects the circadian clock;
      however, little is known about its relative role in controlling metabolic
      variations in vivo. Here we used high time-resolution sampling in Drosophila at
      every 2 h to measure metabolite outputs using a liquid-chromatography tandem mass
      spectrometry (LC-MS/MS) approach. Over 14% of detected metabolites oscillated
      with circadian periodicity under light-dark (LD) cycles. Many metabolites peaked
      shortly after lights-on, suggesting responsiveness to feeding and/or activity
      rather than the preactivity anticipation, as observed in previous transcriptomics
      analyses. Roughly 9% of measured metabolites uniquely oscillated under constant
      darkness (DD), suggesting that metabolite rhythms are associated with the
      transcriptional clock machinery. Strikingly, metabolome differences between LD
      and constant darkness were observed only during the light phase, highlighting the
      importance of photic input. Clock mutant flies exhibited strong 12-h ultradian
      rhythms, including 4 carbohydrate species with circadian periods in wild-type
      flies, but lacked 24-h circadian metabolic oscillations. A meta-analysis of these
      results with previous circadian metabolomics experiments uncovered the
      possibility of conserved rhythms in amino acids, keto-acids, and sugars across
      flies, mice, and humans and provides a basis for exploring the chrono-metabolic
      connection with powerful genetic tools in Drosophila.

PMID- 29355067
TI  - An attempt to measure the diametric relationship between slow and quick phases of
      nystagmus.
AB  - OBJECTIVE: To investigate whether our original method can precisely evaluate the
      angle between slow and quick phases of nystagmus (vector angle) and to determine
      whether vector angle analysis is helpful in differentiating between horizontal
      nystagmus and mixed nystagmus with horizontal and vertical components. METHODS:
      We included 20 healthy volunteers, 17 patients with horizontal nystagmus, and 15
      patients with mixed nystagmus. Caloric nystagmus was recorded in healthy
      volunteers; positional nystagmus was recorded in each patient. We extracted the
      velocity of nystagmus from eye movement of each subject and analysed the vector
      angle. RESULTS: In caloric nystagmus, the vector angle approached 180 degrees as
      slow-phase velocity increased, suggesting that our vector angle measurement is
      more reliable with faster nystagmus. Importantly, in horizontal nystagmus from
      peripheral vestibular disease, the vector angle similarly approached 180 degrees
      as slow-phase velocity increased; in contrast, the vector angle in cases of mixed
      nystagmus from vertebrobasilar insufficiency or spinocerebellar degeneration
      significantly differed from the angle of caloric nystagmus. CONCLUSIONS: Vector
      angle analysis using our original algorithm can precisely evaluate the diametric
      relationship in vestibular nystagmus; it may be helpful in diagnosis of non
      peripheral vestibular disorders.

PMID- 29355068
TI  - Predicting performance of junior doctors: Association of workplace based
      assessment with demographic characteristics, emotional intelligence, selection
      scores, and undergraduate academic performance.
AB  - INTRODUCTION: Predicting workplace performance of junior doctors from before
      entry or during medical school is difficult and has limited available evidence.
      This study explored the association between selected predictor variables and
      workplace based performance in junior doctors during their first postgraduate
      year. METHODS: Two cohorts of medical students (n = 200) from one university in
      Western Australia participated in the longitudinal study. Pearson correlation
      coefficients and multivariate analyses utilizing linear regression were used to
      assess the relationships between performance on the Junior Doctor Assessment Tool
      (JDAT) and its sub-components with demographic characteristics, selection scores
      for medical school entry, emotional intelligence, and undergraduate academic
      performance. RESULTS: Grade Point Average (GPA) at the completion of
      undergraduate studies had the most significant association with better
      performance on the overall JDAT and each subscale. Increased age was a negative
      predictor for junior doctor performance on the Clinical management subscale and
      understanding emotion was a predictor for the JDAT Communication subscale.
      Secondary school performance measured by Tertiary Entry Rank on entry to medical
      school score predicted GPA but not junior doctor performance. DISCUSSION: The GPA
      as a composite measure of ability and performance in medical school is associated
      with junior doctor assessment scores. Using this variable to identify students at
      risk of difficulty could assist planning for appropriate supervision, support,
      and training for medical graduates transitioning to the workplace.

PMID- 29355069
TI  - Hearing results after type III tympanoplasty: incus transposition versus PORP. A
      systematic review.
AB  - OBJECTIVE: The objective of this study is to compare hearing improvements in the
      air-bone gap (ABG) after type III tympanoplasties, comparing between incus
      transposition (IT) and partial ossicular replacement prosthesis (PORP). MATERIALS
      AND METHODS: Publications in English were searched in PUBMED database and were
      systematically reviewed. A total of 14 articles were included, obtaining 1055
      patients, 614 for the IT group and 441 for the PORP group. Preoperative ABG,
      postoperative ABG, dB gain and ABG closure rate were compared. RESULTS: IT group:
      preoperative ABG of 31.74 dB (SD 10.51); postoperative ABG of 18.97 dB (SD 10.6);
      dB gain of 12.76 dB (SD 14.97); and ABG closure rate of 64.48%. PORP group:
      preoperative ABG of 28.02 dB (SD 10.47); postoperative ABG of 16.27 dB (SD
      10.45); dB gain of 11.75 (SD 15.02); and ABG closure rate of 71.32%. No
      significant statistical difference was found in dB mean gain between groups (p >
      .05), although a difference was found in the ABG closure rate between groups
      favouring PORP series (p < .05). CONCLUSION: An improvement in hearing results
      was observed within both groups after type III tympanoplasty. There is no
      difference in decibels gained between both ossiculoplasty materials, but a better
      closure rate (%) was observed in the PORP group.

PMID- 29355070
TI  - Engaging the Underrepresented Sex: Male Participation in Chronic Disease Self
      Management Education (CDSME) Programs.
AB  - Females are more likely than males to participate in evidence-based health
      promotion and disease prevention programs targeted for middle-aged and older
      adults. Despite the availability and benefits of Stanford's Chronic Disease Self
      Management Education (CDSME) programs, male participation remains low. This study
      identifies personal characteristics of males who attended CDSME program workshops
      and identifies factors associated with successful intervention completion. Data
      were analyzed from 45,375 male CDSME program participants nationwide. Logistic
      regression was performed to examine factors associated with workshop attendance.
      Males who were aged 65-79 (OR = 1.27, p < .001), Hispanic (OR = 1.22, p < .001),
      African American (OR = 1.13, p < .001), Asian/Pacific Islander (OR = 1.26, p <
      .001), Native Hawaiian (OR = 3.14, p < .001), and residing in nonmetro areas (OR
      = 1.26, p < .001) were more likely to complete the intervention. Participants
      with 3+ chronic conditions were less likely to complete the intervention (OR =
      0.87, p < .001). Compared to health-care organization participants, participants
      who attended workshops at senior centers (OR = 1.38, p < .001),
      community/multipurpose facilities (OR = 1.21, p < .001), and faith-based
      organizations (OR = 1.37, p < .001) were more likely to complete the
      intervention. Men who participated in workshops with more men were more likely to
      complete the intervention (OR = 2.14, p < .001). Once enrolled, a large
      proportion of males obtained an adequate intervention dose. Findings highlight
      potential strategies to retain men in CDSME programs, which include diversifying
      workshop locations, incorporating Session Zero before CDSME workshops, and using
      alternative delivery modalities (e.g., online).

PMID- 29355071
TI  - Gay and Bisexual Men's Perceptions of HIV Risk in Various Relationships.
AB  - Men who have sex with men (MSM) bear a disproportionate burden of HIV incidence
      in the United States. Previous study of sexual decision-making and HIV risk among
      MSM has not accounted for relationship dynamics. Further research must examine
      this connection between relationship dynamics and sexual decision-making,
      especially regarding condomless anal intercourse. This study analyzes data
      gathered from gay and bisexual men regarding their sexual partners and sexual
      decision-making over a 10-week period through personal relationship diaries
      (PRDs) and a follow-up in-depth interview (IDI). Through coding and extraction of
      relationship dynamics, key patterns of participants' sexual decision-making
      processes were examined based on relationship type, which was categorized by
      commitment, formality, and sexual agreement. Participants' sexual relationships
      can be divided into five categories: (a) Uncommitted, one time, (b) Uncommitted,
      ongoing, (c) Transitioning or unknown commitment, (d) Committed, nonmonogamous,
      and (e) Committed, monogamous. These five categories correspond to patterns in
      sexual decision making and consequent sexual risk-taking behaviors. Each of these
      influence HIV risk within male-male sexual encounters in a particular manner, and
      understanding these is important for appropriately tailored HIV prevention
      interventions for MSM. Recommendations are included for interventions seeking to
      address HIV risk across a wide variety of MSM sexual relationships.

PMID- 29355072
TI  - Topiramate-Induced Chest Pain: A Case Report.
AB  - BACKGROUND: Topiramate, an anticonvulsant used for prophylaxis of migraines and
      epilepsy, is commonly associated with adverse effects of cognitive dulling and
      fatigue. Chest pain is a potential adverse effect that to our knowledge has not
      been reported with the use of topiramate. CASE PRESENTATION: We present the case
      of a 38-year-old female with a seizure disorder who experienced chest pain after
      the first dose of topiramate. On day 1, she presented to the emergency
      department, was admitted, and over the course of 3 days had a chest X-ray,
      electrocardiogram (ECG), and echocardiogram, and her vitals, basic metabolic
      panel, complete blood counts, troponin, and d-dimer levels were monitored. The
      chest pain improved when the topiramate was held. No identifiable causes of chest
      pain were apparent, other than the topiramate. DISCUSSION: The Naranjo
      probability scale was utilized to determine the causality of topiramate. The
      resulting score of 3 indicates that it is possible that the chest pain was due to
      the topiramate. CONCLUSION: This report demonstrates an example of a patient who
      experienced chest pain possibly caused by the initiation of topiramate. The
      objective of this case report is to increase the awareness of chest pain as an
      adverse effect of topiramate.

PMID- 29355073
TI  - Estimating causal log-odds ratio using the case-control sample and its
      application in the pharmaco-epidemiology study.
AB  - One important goal in pharmaco-epidemiology studies is to understand the causal
      relationship between drug exposures and their clinical outcomes, including
      adverse drug events. In order to achieve this goal, however, we need to resolve
      several challenges. Most of pharmaco-epidemiology data are observational and
      confounding is largely present due to many co-medications. The pharmaco
      epidemiology study data set is often sampled from large medical record databases
      using a matched case-control design, and it may not be representative of the
      original patient population in the medical record databases. Data analysis method
      needs to handle a large sample size that cannot be handled using existing
      statistical analysis packages. In this paper, we tackle these challenges both
      methodologically and computationally. We propose a conditional causal log-odds
      ratio (OR) definition to characterize causal effects of drug exposures on a
      binary adverse drug event adjusting for individual level confounders. Using a
      case-control design, we present a propensity score estimation using only case
      samples and we provide sufficient conditions for the consistency of the
      estimation of the causal log-odds ratio using case-based propensity scores.
      Computationally, we implement a principle component analysis to reduce high
      dimensional confounders. Extensive simulation studies are performed to
      demonstrate superior performance of our method to existing methods. Finally, we
      apply the proposed method to analyze drug-induced myopathy data sampled from a de
      identified subset of medical record database (close to 5 million patient
      records), The Indiana Network for Patient Care. Our method identified 70 drug
      induced myopathy ( p < 0.05) out 72 drugs, which have myoathy side effects on
      their FDA drug labels. These 70 drugs include three statins who are known for
      their myopathy side effects.

PMID- 29355074
TI  - Medical student psychological distress and academic performance.
AB  - INTRODUCTION: The impact of medical student psychological distress on academic
      performance has not been systematically examined. This study provided an
      opportunity to closely examine the potential impacts of workplace and study
      related stress factors on student's psychological distress and their academic
      performance during their first clinical year. METHODS: This one-year prospective
      cohort study was performed at a tertiary hospital based medical school in
      Melbourne, Australia. Students completed a questionnaire at three time points
      during the year. The questionnaire included the validated Kessler psychological
      distress scale (K10) and the General Health Questionnaire-28 (GHQ-28), as well as
      items about sources of workplace stress. Academic outcome scores were aggregated
      and correlated with questionnaire results. RESULTS: One hundred and twenty six
      students participated; 126 (94.7%), 102 (76.7%), and 99 (74.4%) at time points
      one, two, and three, respectively. 33.1% reported psychological distress at time
      point one, increasing to 47.4% at time point three. There was no correlation
      between the K10 scores and academic performance. There was weak negative
      correlation between the GHQ-28 at time point three and academic performance.
      Keeping up to date with knowledge, need to do well and fear of negative feedback
      were the most common workplace stress factors. CONCLUSIONS: Poor correlation was
      noted between psychological distress and academic performance.

PMID- 29355075
TI  - Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair
      Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer.
AB  - Purpose Nivolumab provides clinical benefit (objective response rate [ORR], 31%;
      95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS],
      73%) in previously treated patients with DNA mismatch repair-deficient
      (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer
      (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety
      results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest
      single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are
      reported. Patients and Methods Patients received nivolumab 3 mg/kg plus
      ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg
      once every 2 weeks. Primary end point was investigator-assessed ORR. Results Of
      119 patients, 76% had received >= two prior systemic therapies. At median follow
      up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and
      disease control rate for >= 12 weeks was 80%. Median duration of response was not
      reached; most responses (94%) were ongoing at data cutoff. Progression-free
      survival rates were 76% (9 months) and 71% (12 months); respective OS rates were
      87% and 85%. Statistically significant and clinically meaningful improvements
      were observed in patient-reported outcomes, including functioning, symptoms, and
      quality of life. Grade 3 to 4 treatment-related adverse events (AEs) occurred in
      32% of patients and were manageable. Patients (13%) who discontinued treatment
      because of study drug-related AEs had an ORR (63%) consistent with that of the
      overall population. Conclusion Nivolumab plus ipilimumab demonstrated high
      response rates, encouraging progression-free survival and OS at 12 months,
      manageable safety, and meaningful improvements in key patient-reported outcomes.
      Indirect comparisons suggest combination therapy provides improved efficacy
      relative to anti-programmed death-1 monotherapy and has a favorable benefit-risk
      profile. Nivolumab plus ipilimumab provides a promising new treatment option for
      patients with dMMR/MSI-H mCRC.

PMID- 29355076
TI  - [Trauma First - an Outpatient, Cognitive-Behavioural Intervention for Children
      and Adolescents With Trauma-Related Disorders: a Pilot Study].
AB  - Objective: Although traumatic experiences are one of the most important causes
      for psychiatric disorders in childhood and adulthood, trauma-specific
      intervention approaches are rarely applied in German outpatient clinics. The aim
      of the present pilot study was to evaluate a manualized, outpatient, cognitive
      behavioural intervention programme ("Trauma First") for children and youths with
      trauma and stress-related disorders. We hypothesized that there would be specific
      improvements in PTSD symptoms as well as in depression, anxiety, and behavioural
      problems following the structured intervention Programme. Method: The pilot study
      consisted of a pre-post-test design without a control group. Symptom severity of
      33 children and youths (age: 10-15 years; 54.5 % female) with traumatic
      experiences was assessed by self-ratings and parent-ratings before and after the
      treatment. Results: After the treatment, improvements were found in children's
      PTSD symptoms, depression, anxiety, and behavioural problems (Cohen's d: 0.51
      1.49). A trend was found showing improvement of children's life satisfaction.
      Effect sizes were comparable with results from meta-analyses. Conclusions: The
      pilot study provided first evidence for the effectiveness of "Trauma First" under
      ecologically valid conditions. This study is a first step in the evaluation
      process of psychotherapeutic effectiveness, which should be continued by
      conducting a randomized-controlled study design.

PMID- 29355078
TI  - Therapists' and clients' ratings of real relationship, attachment, therapist self
      disclosure, and treatment progress.
AB  - OBJECTIVE: While there has been much research on the role of the working alliance
      in psychotherapy, researchers only recently began investigating the role of the
      real relationship in treatment. METHODS: In the current study on therapist and
      client dyads, we used actor-partner interdependence modeling (APIM) to examine
      associations between therapists' and clients' ratings of the real relationship,
      therapist self-disclosure, attachment, and treatment progress. APIM analyses
      allowed for an examination into how therapists' and clients' views of a
      particular phenomenon might affect their own ratings (actor), as well as the
      others' (partner) ratings of that same phenomenon. RESULTS: Significant negative
      associations between therapist self-reported attachment anxiety and avoidance and
      therapist-rated real relationship and treatment progress. Significant positive
      associations were found between client-rated real relationship and client-rated
      treatment progress. These results and others are discussed in the context of the
      literature along with implications for future research in this area. Clinical or
      methodological significance of this article: The current study has uncovered
      evidence that therapists' ratings of their attachment anxiety and avoidance are
      negatively and significantly associated with their ratings of the real
      relationship and of treatment progress. The results also indicate that both
      therapists' and clients' ratings of the real relationship were positively and
      significantly associated with their ratings of clients' treatment progress.

PMID- 29355077
TI  - The COP9 signalosome inhibits Cullin-RING E3 ubiquitin ligases independently of
      its deneddylase activity.
AB  - The COP9 signalosome inhibits the activity of Cullin-RING E3 ubiquitin ligases by
      removing Nedd8 modifications from their Cullin subunits. Neddylation renders
      these complexes catalytically active, but deneddylation is also necessary for
      them to exchange adaptor subunits and avoid auto-ubiquitination. Although
      deneddylation is thought to be the primary function of the COP9 signalosome,
      additional activities have been ascribed to some of its subunits. We recently
      showed that COP9 subunits protect the transcriptional repressor and tumor
      suppressor Capicua from two distinct modes of degradation. Deneddylation by the
      COP9 signalosome inactivates a Cullin 1 complex that ubiquitinates Capicua
      following its phosphorylation by MAP kinase in response to Epidermal Growth
      Factor Receptor signaling. The CSN1b subunit also stabilizes unphosphorylated
      Capicua to control its basal level, independently of the deneddylase function of
      the complex. Here we further examine the importance of deneddylation for COP9
      functions in vivo. We use an uncleavable form of Nedd8 to show that preventing
      deneddylation does not reproduce the effects of loss of COP9. In contrast, in the
      presence of COP9, conjugation to uncleavable Nedd8 renders Cullins unable to
      promote the degradation of their substrates. Our results suggest that
      irreversible neddylation prolongs COP9 binding to and inhibition of Cullin-based
      ubiquitin ligases.

PMID- 29355079
TI  - "I Don't Know That I've Ever Felt Like I Got the Full Story": A Qualitative Study
      of Courtroom Interactions Between Judges and Litigants in Domestic Violence
      Protective Order Cases.
AB  - One in three U.S. women has experienced intimate partner violence (IPV) and many
      seek domestic violence protective orders (DVPOs) for secondary IPV prevention.
      Because judges have considerable autonomy making DVPO decisions, there is a need
      to describe how courtroom interactions and information available to judges may
      influence DVPO dispositions. We conducted DVPO hearing observations and phone
      interviews with District Court Judges. Qualitative themes emerged that may
      influence judges' decision making in DVPO hearings: case information
      availability, judge engagement level, and litigant credibility. Recommendations
      include more time for judges to review case files, IPV-related training for
      judges, and increased court advocate use.

PMID- 29355080
TI  - Gathering, strategizing, motivating and celebrating: the team huddle in a
      teaching general practice.
AB  - OBJECTIVES: To understand how implementing a daily team huddle affected the
      function of a complex interprofessional team including learners. DESIGN: A
      qualitative descriptive study using semi-structured interviews in focus groups.
      SETTING: An academic general practice teaching practice. PARTICIPANTS: All
      members of one interprofessional team, including nurses, general practitioners,
      junior doctors, and support staff. METHOD: Focus group interviews using semi
      structured guidance were transcribed and the results analysed using qualitative
      content analysis. MAIN FINDINGS: Four interrelated themes were identified:
      communication and knowledge sharing; efficiency of care; relationship and team
      building; and shared responsibility for team function. The implementation of the
      daily team huddle was seen by participants to enhance the collaboration within
      the team and to contribute to work life enjoyment. Participants perceived that
      problems were anticipated and solved quickly. Clinical updates and information
      about patients benefited the team including learners. Junior doctors quickly
      understood the scope of practice of other team members, but some felt reluctant
      to offer clinical opinions. CONCLUSION: The implementation of a daily team huddle
      was viewed as worthwhile by this large interprofessional general practice team.
      The delivery of patient care was more efficient, knowledge was readily
      distributed, and problem solving was shared across the team, including junior
      doctors.

PMID- 29355082
TI  - Use of interval estimations in design and evaluation of multiregional clinical
      trials with continuous outcomes.
AB  - Multiregional clinical trials have been accepted in recent years as a useful
      means of accelerating the development of new drugs and abridging their approval
      time. The statistical properties of multiregional clinical trials are being
      widely discussed. In practice, variance of a continuous response may be different
      from region to region, but it leads to the assessment of the efficacy response
      falling into a Behrens-Fisher problem-there is no exact testing or interval
      estimator for mean difference with unequal variances. As a solution, this study
      applies interval estimations of the efficacy response based on Howe's, Cochran
      Cox's, and Satterthwaite's approximations, which have been shown to have well
      controlled type I error rates. However, the traditional sample size determination
      cannot be applied to the interval estimators. The sample size determination to
      achieve a desired power based on these interval estimators is then presented.
      Moreover, the consistency criteria suggested by the Japanese Ministry of Health,
      Labour and Welfare guidance to decide whether the overall results from the
      multiregional clinical trial obtained via the proposed interval estimation were
      also applied. A real example is used to illustrate the proposed method. The
      results of simulation studies indicate that the proposed method can correctly
      determine the required sample size and evaluate the assurance probability of the
      consistency criteria.

PMID- 29355081
TI  - Defining the relationship between COPD and CVD: what are the implications for
      clinical practice?
AB  - Cardiovascular diseases (CVDs) are arguably the most important comorbidities in
      chronic obstructive pulmonary disease (COPD). CVDs are common in people with
      COPD, and their presence is associated with increased risk for hospitalization,
      longer length of stay and all-cause and CVD-related mortality. The economic
      burden associated with CVD in this population is considerable and the cumulative
      cost of treating comorbidities may even exceed that of treating COPD itself. Our
      understanding of the biological mechanisms that link COPD and various forms of
      CVD has improved significantly over the past decade. But despite broad acceptance
      of the prognostic significance of CVDs in COPD, there remains widespread under
      recognition and undertreatment of comorbid CVD in this population. The reasons
      for this are unclear; however institutional barriers and a lack of evidence-based
      guidelines for the management of CVD in people with COPD may be contributory
      factors. In this review, we summarize current knowledge relating to the
      prevalence and incidence of CVD in people with COPD and the mechanisms that
      underlie their coexistence. We discuss the implications for clinical practice and
      highlight opportunities for improved prevention and treatment of CVD in people
      with COPD. While we advocate more active assessment for signs of cardiovascular
      conditions across all age groups and all stages of COPD severity, we suggest
      targeting those aged under 65 years. Evidence indicates that the increased risks
      for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age
      and thus it is in this age group that the benefits of early intervention may
      prove to be the most effective.

PMID- 29355083
TI  - Editorial.

PMID- 29355084
TI  - Retraction.

PMID- 29355085
TI  - Concurrent criterion validity of a novel portable motion analysis system for
      assessing the landing error scoring system (LESS) test.
AB  - The landing error scoring system (LESS) assesses the quality of a landing after a
      jump. The quality of the jump is usually evaluated using a three-dimensional (3
      D) motion analysis system or a two-dimensional (2-D) video analysis visually
      rated by a clinician. However, both methods have disadvantages. The aim of this
      study was to examine the concurrent validity of a novel portable motion analysis
      system ('PhysiMax System') in assessing the LESS score by comparing it to video
      analysis. The study population included 48 healthy participants (28.45 +/- 5.61
      years), each performing the LESS test while two video cameras and the 'PhysiMax'
      simultaneously recorded the jump. The 'Physimax' system automatically evaluated
      the LESS. Subsequently, the examiners scored the test by viewing the video
      recordings, blinded to the 'PhysiMax' results. The mean LESS score, using the
      video recordings and the 'PhysiMax' was 4.77 (+/-2.29) and 5.15 (+/-2.58),
      respectively, (ICC = 0.80, 95% confidence intervals 0.65-0.87), mean absolute
      differences 1.13 (95% confidence intervals; 0.79-1.46). The results indicate a
      high consensus between the methods of measurement. The 'Physimax' system's main
      advantages are portability, objective evaluation and immediate availability of
      results. The system can be used by athletic trainers and physiotherapists in the
      clinic and in the field for jumping assessment.

PMID- 29355086
TI  - A Trauma-Informed Analysis of the Violence Against Women Act's Provisions for
      Undocumented Immigrant Women.
AB  - Immigrant women in the United States are among the groups disproportionately
      affected by intimate partner violence (IPV). Undocumented immigrants generally
      have fewer resources for coping with violence and may experience a range of
      personal, cultural, and immigration status-related barriers to reporting violence
      and accessing help. Thus, undocumented immigrant victims of IPV could benefit
      significantly from policies that promote access to trauma-informed services and
      legal options. This article applies a trauma-informed policy analysis framework
      to the Violence Against Women Act's immigration protections to demonstrate how
      the Act's U-Visa provisions and implementation practices could be improved by
      incorporating trauma-informed principles of trustworthiness and transparency,
      empowerment, choice, safety, collaboration, and intersectionality.

PMID- 29355089
TI  - The 2018 SLAS Technology Ten: Translating Life Sciences Innovation.

PMID- 29355087
TI  - Fast and Label-Free Isolation of Circulating Tumor Cells from Blood: From a
      Research Microfluidic Platform to an Automated Fluidic Instrument, VTX-1 Liquid
      Biopsy System.
AB  - Tumor tissue biopsies are invasive, costly, and collect a limited cell population
      not completely reflective of patient cancer cell diversity. Circulating tumor
      cells (CTCs) can be isolated from a simple blood draw and may be representative
      of the diverse biology from multiple tumor sites. The VTX-1 Liquid Biopsy System
      was designed to automate the isolation of clinically relevant CTC populations,
      making the CTCs available for easy analysis. We present here the transition from
      a cutting-edge microfluidic innovation in the lab to a commercial, automated
      system for isolating CTCs directly from whole blood. As the technology evolved
      into a commercial system, flexible polydimethylsiloxane microfluidic chips were
      replaced by rigid poly(methyl methacrylate) chips for a 2.2-fold increase in cell
      recovery. Automating the fluidic processing with the VTX-1 further improved
      cancer cell recovery by nearly 1.4-fold, with a 2.8-fold decrease in
      contaminating white blood cells and overall improved reproducibility. Two
      isolation protocols were optimized that favor either the cancer cell recovery (up
      to 71.6% recovery) or sample purity (<=100 white blood cells/mL). The VTX-1's
      performance was further tested with three different spiked breast or lung cancer
      cell lines, with 69.0% to 79.5% cell recovery. Finally, several cancer research
      applications are presented using the commercial VTX-1 system.

PMID- 29355090
TI  - Combining morphology and molecular data to improve Drosophila paulistorum
      (Diptera, Drosophilidae) taxonomic status.
AB  - The willistoni species subgroup has been the subject of several studies since the
      latter half of the past century and is considered a Neotropical model for
      evolutionary studies, given the many levels of reproductive isolation and
      different evolutionary stages occurring within them. Here we present for the
      first time a phylogenetic reconstruction combining morphological characters and
      molecular data obtained from 8 gene fragments (COI, COII, Cytb, Adh, Ddc, Hb, kl
      3 and per). Some relationships were incongruent when comparing morphological and
      molecular data. Also, morphological data presented some unresolved polytomies,
      which could reflect the very recent divergence of the subgroup. The total
      evidence phylogenetic reconstruction presented well-supported relationships and
      summarized the results of all analyses. The diversification of the willistoni
      subgroup began about 7.3 Ma with the split of D. insularis while D.paulistorum
      complex has a much more recent diversification history, which began about 2.1 Ma
      and apparently has not completed the speciation process, since the average time
      to sister species separation is one million years, and some entities of the D.
      paulistorum complex diverge between 0.3 and 1 Ma. Based on the obtained data, we
      propose the categorization of the former "semispecies" of D. paulistorum as a
      subspecies and describe the subspecies D. paulistorum amazonian, D. paulistorum
      andeanbrazilian, D. paulistorum centroamerican, D. paulistorum interior, D.
      paulistorum orinocan and D. paulistorum transitional.

PMID- 29355091
TI  - The relationship between meeting of recommendations on physical activity for
      health and perceived work ability among white-collar workers.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between meeting
      recommendations on physical activity for health in leisure-time and the ability
      to work among Polish white-collar workers. METHODS: The study used a cross
      sectional design with a convenience sample of 360 white-collar workers.
      Participants recorded 7-day physical activity logs, including form, duration and
      intensity of leisure-time physical activities. The results were compared to
      health recommendations. A standardized Work Ability Index (WAI) questionnaire was
      used in assessing the ability to work. RESULTS: Participants who met health
      recommendations achieved higher scores of the WAI (mean score = 41.93) in
      comparison to those who were not sufficiently physically active (mean score =
      39.35) (p < .001). The results of binary logistic regression show that meeting
      health-related physical activity recommendations almost double the odds of
      reaching at least good work ability (OR = 1.94, 95% CI = 1.12-3.36). CONCLUSIONS:
      Meeting leisure-time physical activity recommendations (especially the criterion
      of vigorous physical activity) is significantly related to higher self-assessed
      ability to work among white-collar workers.

PMID- 29355092
TI  - Sodium bicarbonate ingestion increases glycolytic contribution and improves
      performance during simulated taekwondo combat.
AB  - PURPOSE: To investigate the effect of sodium bicarbonate (NaHCO3) on performance
      and estimated energy system contribution during simulated taekwondo combat.
      METHODS: Nine taekwondo athletes completed two experimental sessions separated by
      at least 48 h. Athletes consumed 300 mg/kg body mass of NaHCO3 or placebo (CaCO3)
      90 min before the combat simulation (three rounds of 2 min separated by 1 min
      passive recovery), in a double-blind, randomized, repeated-measures crossover
      design. All simulated combat was filmed to quantify the time spent fighting in
      each round. Lactate concentration [La-] and rating of perceived exertion (RPE)
      were measured before and after each round, whereas heart rate (HR) and the
      estimated contribution of the oxidative (WOXI), ATP (adenosine triphosphate)
      phosphocreatine (PCr) (WPCR), and glycolytic (W[La-]) systems were calculated
      during the combat simulation. RESULTS: [La-] increased significantly after NaHCO3
      ingestion, when compared with the placebo condition (+14%, P = 0.04, d = 3.70).
      NaHCO3 ingestion resulted in greater estimated glycolytic energy contribution in
      the first round when compared with the placebo condition (+31%, P = 0.01, d =
      3.48). Total attack time was significantly greater after NaHCO3 when compared
      with placebo (+13%, P = 0.05, d = 1.15). WOXI, WPCR, VO2, HR and RPE were not
      different between conditions (P > 0.05). CONCLUSION: NaHCO3 ingestion was able to
      increase the contribution of glycolytic metabolism and, therefore, improve
      performance during simulated taekwondo combat.

PMID- 29355093
TI  - Dietary fat intake associated with bone mineral density among visfatin genotype
      in obese people.
AB  - Osteoporosis and adipose tissue are closely related with many contradictions.
      Visfatin is an adipokine that is related to osteoporosis and adiposity. This
      nutrigenomics study examined the interaction between visfatin genotypes and
      dietary fat intake, with regard to bone mineral density (BMD) among an obese
      population. In this cross-sectional study, 336 subjects were enrolled; the mean
      age was 38.25 (sd 11.69) years and the mean BMI was 31.79 (sd 4.77) kg/m2.
      Laboratory measurements were lipid profile, insulin and fasting blood sugar. Bone
      density measurements were assessed by dual-energy X-ray absorptiometry. Dietary
      data were collected through a 3-d 24-h dietary recall. Genotyping for visfatin
      gene SNP (rs2110385) was performed by the PCR-restriction fragment length
      polymorphism method. The frequency of GG, GT and TT genotypes were 33.92 48.51
      and 17.54 %, respectively, and 86.6 % of participants were women. The results
      showed that subjects with TT genotypes had significantly higher lumbar BMD, T
      score and z score (P<0.0001). After categorisation by percentage of fat intake
      (30 % of total energy content as a cut-off point), no interaction was found, but
      when categorised by fat types, we found an interaction between visfatin genotypes
      and dietary PUFA intake in terms of the hip T score and z score (P=0.043, B= 
      0.08; P=0.04, B= -0.078, respectively). There was a significant relationship
      between high PUFA intake and lower energy and protein intake. When participants
      were categorised by median PUFA intake (22.8 g), it was concluded that subjects
      with GG genotype who had high PUFA-intake diets had lower hip z scores and T
      scores, unlike the other genotypes.

PMID- 29355094
TI  - The association and dose-response relationship between dietary intake of alpha
      linolenic acid and risk of CHD: a systematic review and meta-analysis of cohort
      studies.
AB  - Previous studies show inconsistent associations between alpha-linolenic acid
      (ALA) and risk of CHD. We aimed to examine an aggregate association between ALA
      intake and risk of CHD, and assess for any dose-response relationship. We
      searched the PubMed, EMBASE and Web of Science databases for prospective cohort
      studies examining associations between ALA intake and CHD, including composite
      CHD and fatal CHD. Data were pooled using random-effects meta-analysis models,
      comparing the highest category of ALA intake with the lowest across studies.
      Subgroup analysis was conducted based on study design, geographic region, age and
      sex. For dose-response analyses, we used two-stage random-effects dose-response
      models. In all, fourteen studies of thirteen cohorts were identified and included
      in the meta-analysis. The pooled results showed that higher ALA intake was
      associated with modest reduced risk of composite CHD (risk ratios (RR)=0.91; 95 %
      CI 0.85, 0.97) and fatal CHD (RR=0.85; 95 % CI 0.75, 0.96). The analysis showed a
      J-shaped relationship between ALA intake and relative risk of composite CHD (chi
      2=21.95, P<0.001). Compared with people without ALA intake, only people with ALA
      intake <1.4 g/d showed reduced risk of composite CHD. ALA intake was linearly
      associated with fatal CHD - every 1 g/d increase in ALA intake was associated
      with a 12 % decrease in fatal CHD risk (95 % CI -0.21, -0.04). Though a higher
      dietary ALA intake was associated with reduced risk of composite and fatal CHD,
      the excess composite CHD risk at higher ALA intakes warrants further
      investigation, especially through randomised controlled trials.

PMID- 29355096
TI  - Invited commentary in response to: usual nutrient intake adequacy among young,
      rural Zambian children.

PMID- 29355095
TI  - Beneficial effects of consumption of acerola, cashew or guava processing by
      products on intestinal health and lipid metabolism in dyslipidaemic female Wistar
      rats.
AB  - This study assessed the effects of diet supplementation with industrial
      processing by-products of acerola (Malpighia emarginata D.C.), cashew (Anacardium
      occidentale L.) and guava (Psidium guajava L.) fruit on the intestinal health and
      lipid metabolism of female Wistar rats with diet-induced dyslipidaemia. Female
      rats were randomly divided into five groups: healthy control, dyslipidaemic
      control and dyslipidaemic experimental receiving acerola, cashew or guava
      processing by-products. Fruit processing by-products were administered (400 mg/kg
      body weight) via orogastric administration for 28 consecutive days. Acerola,
      cashew and guava by-products caused body weight reduction (3.42, 3.08 and 5.20 %,
      respectively) in dyslipidaemic female rats. Dyslipidaemic female rats receiving
      fruit by-products, especially from acerola, presented decreased faecal pH,
      visceral fat, liver fat and serum lipid levels, as well as increased faecal
      moisture, faecal fat excretion, faecal Bifidobacterium spp. and Lactobacillus
      spp. counts and amounts of organic acids in faeces. Administration of the tested
      fruit processing by-products protected colon and liver from tissue damage (e.g.
      destruction of liver and colon cells and increased fat deposition in hepatocytes)
      induced by dyslipidaemic diet. Dietary fibres and phenolic compounds in tested
      fruit by-products may be associated with these positive effects. The industrial
      fruit processing by-products studied, mainly from acerola, exert functional
      properties that could enable their use to protect the harmful effects on
      intestinal health and lipid metabolism caused by dyslipidaemic diet.

PMID- 29355098
TI  - Perceptions of political leaders.
AB  - Partisan identification is a fundamental force in individual and mass political
      behavior around the world. Informed by scholarship on human sociality,
      coalitional psychology, and group behavior, this research argues that partisan
      identification, like many other group-based behaviors, is influenced by forces of
      evolution. If correct, then party identifiers should exhibit adaptive behaviors
      when making group-related political decisions. The authors test this assertion
      with citizen assessments of the relative physical formidability of competing
      leaders, an important adaptive factor in leader evaluations. Using original and
      novel data collected during the contextually different 2008 and 2012 U.S.
      presidential elections, as well as two distinct measures obtained during both
      elections, this article presents evidence that partisans overestimate the
      physical stature of the presidential candidate of their own party compared with
      the stature of the candidate of the opposition party. These findings suggest that
      the power of party identification on political behavior may be attributable to
      the fact that modern political parties address problems similar to the problems
      groups faced in human ancestral times.

PMID- 29355097
TI  - Usual nutrient intake adequacy among young, rural Zambian children.
AB  - Inadequate nutrient intakes put children at risk for impaired growth and
      development. We described diet, usual intakes of energy and macro- and
      micronutrients and prevalence of nutrient intake adequacies among 4-8-year-old
      Zambian children. Children not yet in school and living in Mkushi District,
      Central Province, Zambia were enrolled into an efficacy trial of pro-vitamin A
      biofortified maize. Children in the non-intervened arm were included in this
      analysis (n 202). Dietary intake data were collected by tablet-based 24-h recall
      on a monthly basis over the 6-month trial. Observed nutrient intakes were derived
      from reported food quantities, standard recipes and food composition tables.
      Usual nutrient intake distributions were modelled based on observed intakes.
      Prevalence of inadequacy was estimated by comparing the usual nutrient intake
      distribution to the nutrient requirement distribution. Frequency and quantity of
      consumption of commonly reported foods were described and key sources of energy
      and nutrients were identified. Median usual energy intake was 6422 kJ/d (1535
      kcal/d). Most childrens' macronutrient intakes fell within recommended ranges (74
      98 %). Estimated prevalences of inadequate intakes of Fe, folate, vitamin B12 and
      Ca were 25, 57, 76 and >99 %, respectively. Estimated prevalences of inadequacy
      for other micronutrients were low (0.1-2.2 %). Commonly consumed foods included
      maize, vegetable oil, tomatoes, rape leaves and small fish (>0.6 servings/d),
      whereas meat, eggs or dairy were rarely eaten (<0.2 servings/d). These findings
      suggest that the heavily plant-based diet of rural Zambian children provides
      inadequate Ca, folate, vitamin B12 and Fe to meet recommended nutrient intakes.

PMID- 29355099
TI  - Speaking through the body.
AB  - When people speak, they gesture. However, is the audience watching a speaker who
      is sensitive to this link? We translated the body movements of politicians into
      stick-figure animations and separated the visual from the audio channel. We then
      asked participants to match a selection of five audio tracks (including the
      correct one) with the stick-figure animations. The participants made correct
      decisions in 65% of all cases (chance level of 20%). Matching voices with
      animations was less difficult when politicians showed expansive movements and
      spoke with a loud voice. Thus, people are sensitive to the link between motion
      cues and vocal cues, and this link appears to become even more apparent when a
      speaker shows expressive behaviors. Future work will have to refine and validate
      the methods applied and investigate how mismatches between communication channels
      affect the impressions that people form of politicians.

PMID- 29355100
TI  - Effects of disease salience and xenophobia on support for humanitarian aid.
AB  - This article examines how disease salience influences attitudes toward two types
      of humanitarian aid: sending foreign aid and housing refugees. Some have argued
      that disease salience increases levels of out-group prejudice through what is
      referred to as the behavioral immune system (BIS), and this increase in out-group
      prejudice works to shape policy attitudes. However, an alternative mechanism that
      may explain the effects of disease salience is contamination fear, which would
      suggest there is no group bias in the effects of disease threat. Existing work
      largely interprets opposition to policies that assist out-groups as evidence of
      out-group prejudice. We suggest it is necessary to separate measures of out-group
      animosity from opinions toward specific policies to determine whether increased
      out-group prejudice rather than fear of contamination is the mechanism by which
      disease salience impacts policy attitudes. Across two experiments, disease
      salience is shown to significantly decrease support for humanitarian aid, but
      only in the form of refugee support. Furthermore, there is converging evidence to
      suggest that any influence of disease salience on aid attitudes is not caused by
      a corresponding increase in xenophobia. We suggest that the mechanism by which
      disease threat influences policy attitudes is a general fear of contamination
      rather than xenophobia. These findings go against an important hypothesized
      mechanism of the BIS and have critical implications for the relationship between
      disease salience and attitudes toward transnational policies involving
      humanitarian aid.

PMID- 29355101
TI  - Displays of emotion and citizen support for Merkel and Gysi.
AB  - Emotional appeals have always been an important instrument in the mobilization of
      political support in modern societies. As found in several experimental studies
      from the United States, the emotions displayed by leading politicians in their
      televised public appearances have an impact on the political attitudes and
      behaviors of the public. Positive emotions such as joy or happiness, pride, and
      amusement elicit a more positive assessment of politicians, whereas showing
      negative emotions such as anger or outrage often diminishes the public's support.
      This transfer of emotions from sender to recipient has been described as
      "emotional contagion." However, under specific circumstances, emotions expressed
      by politicians can result in counter-empathic reactions among recipients. To
      examine the role of emotions between political leaders and the public in an
      institutional and cultural setting outside the United States, this article
      presents experimental findings on the impact of emotions expressed by two leading
      German politicians on the German public. The study used emotional displays by
      Chancellor Angela Merkel and former parliamentary leader of the Left Party,
      Gregor Gysi, observing how their assessments by the German public changed in
      response to these displays. Consistent with existing research, we discovered
      positive effects on the evaluation of both politicians when they displayed
      positive emotions. However, the impact of negative emotions is different for
      Merkel and Gysi and can be described as contagion in the former and counter
      contagion in the latter case. Furthermore, we found that individual recognition
      of the expressed emotions modified the effect they had on the evaluation of some
      leadership characteristics.

PMID- 29355103
TI  - Conservatism and liberalism predict performance in two nonideological cognitive
      tasks.
AB  - Intuitive thinking would argue that political or ideological orientation does not
      correlate with nonpolitical decisions, and certainly not with nonideological
      cognitive tasks. However, that is what happens in some cases. Previous
      neuropolitics studies have found that liberals are more adept at dealing with
      novel information than conservatives. This finding suggests that conservatives
      and liberals possess different cognitive skills. For the purposes of this
      article, two studies were executed to test whether this difference remained in
      alternative environmental settings. To this end, two novel cognitive tasks were
      designed in which one type of ideology or another was privileged according to the
      cognitive environment created by the tasks. Experimental findings indicate that
      liberals committed fewer errors than conservatives in one kind of cognitive
      environment, while conservatives scored higher in another.

PMID- 29355102
TI  - The biological roots of political extremism.
AB  - Recent research has revealed the complex origins of political identification and
      the possible effects of this identification on social and political behavior.
      This article reports the results of a structural equation analysis of national
      survey data that attempts to replicate the finding that an individual's
      negativity bias predicts conservative ideology. The analysis employs the
      Motivational Activation Measure (MAM) as an index of an individual's positivity
      offset and negativity bias. In addition, information-seeking behavior is assessed
      in relation to traditional and interactive media sources of political
      information. Results show that although MAM does not consistently predict
      political identification, it can be used to predict extremeness of political
      views. Specifically, high negativity bias was associated with extreme
      conservatism, whereas low negativity bias was associated with extreme liberalism.
      In addition, political identification was found to moderate the relationship
      between motivational traits and information-seeking behavior.

PMID- 29355104
TI  - Effects of physical attractiveness on political beliefs.
AB  - Physical attractiveness is an important social factor in our daily interactions.
      Scholars in social psychology provide evidence that attractiveness stereotypes
      and the "halo effect" are prominent in affecting the traits we attribute to
      others. However, the interest in attractiveness has not directly filtered down to
      questions of political behavior beyond candidates and elites. Utilizing measures
      of attractiveness across multiple surveys, we examine the relationship between
      attractiveness and political beliefs. Controlling for socioeconomic status, we
      find that more attractive individuals are more likely to report higher levels of
      political efficacy, identify as conservative, and identify as Republican. These
      findings suggest an additional mechanism for political socialization that has
      further implications for understanding how the body intertwines with the social
      nature of politics.

PMID- 29355105
TI  - Neuropolitics: Twenty years later.
AB  - Neuropolitics is the intersection of neuroscience and political science, and it
      has the interdisciplinary goal of transforming both disciplines. This article
      reviews the past 20 years of work in the field, identifying its roots, some
      overarching themes-reactions to political attitudinal questions and candidates
      faces, identification of political ideology based on brain structure or
      reactivity to nonpolitical stimuli, and racial attitudes-and obstacles to its
      progress. I then explore the methodological and analytical advances that point
      the way forward for the future of neuropolitics. Although the field has been slow
      to develop compared with neurolaw and neuroeconomics, innovations look ripe for
      dramatically improving our ability to model political behaviors and attitudes in
      individuals and predict political choices in mass publics. The coming
      advancements, however, pose risks to our current norms of democratic
      deliberation, and academics need to anticipate and mitigate these risks.

PMID- 29355106
TI  - Shedding light on spawning in jellyfish.
AB  - An opsin receptor has a central role in the production and release of eggs by
      female jellyfish.

PMID- 29355107
TI  - Magnetic and electronic properties of the Cu-substituted Weyl semimetal candidate
      ZrCo2Sn.
AB  - We report that the partial substitution of Cu for Co has a significant impact on
      the magnetic properties of the Heusler-phase Weyl fermion candidate ZrCo2Sn.
      Polycrystalline samples of ZrCo2-x Cu x Sn (x  =  0.0-1.0) exhibited a linearly
      decreasing ferromagnetic transition temperature and similarly decreasing
      saturated magnetic moment on increasing Cu substitution x. Materials with Cu
      contents near x  =  1 and several other quaternary materials synthesized at the
      same x (ZrCoT'Sn (T'  =  Rh, Pd, Ni)) display what appears to be non
      ferromagnetic magnetization behavior with spin glass characteristics. Electronic
      structure calculations suggest that the half-metallic nature of unsubstituted
      ZrCo2Sn is disrupted significantly by the Cu substitutions, leading to the
      breakdown of the magnetization versus electron count guidelines usually followed
      by Heusler phases, and a more typical metallic non-spin-polarized electronic
      structure at high x.

PMID- 29355108
TI  - A review of theoretical study of graphene chemical vapor deposition synthesis on
      metals: nucleation, growth, and the role of hydrogen and oxygen.
AB  - Graphene has attracted intense research interest due to its extraordinary
      properties and great application potential. Various methods have been proposed
      for the synthesis of graphene, among which chemical vapor deposition has drawn a
      great deal of attention for synthesizing large-area and high-quality graphene.
      Theoretical understanding of the synthesis mechanism is crucial for optimizing
      the experimental design for desired graphene production. In this review, we
      discuss the three fundamental steps of graphene synthesis in details, i.e. (1)
      decomposition of carbon feedstocks and formation of various active carbon
      species, (2) nucleation, and (3) attachment and extension. We provide a complete
      scenario of graphene synthesis on metal surfaces at atomistic level by means of
      density functional theory, molecular dynamics (MD), Monte Carlo (MC) and their
      combination and interface with other simulation methods such as quantum
      mechanical molecular dynamics, density functional tight binding molecular
      dynamics, and combination of MD and MC. We also address the latest investigation
      of the influences of the hydrogen and oxygen on the synthesis and the quality of
      the synthesized graphene.

PMID- 29355109
TI  - Model-based observer and feedback control design for a rigid Joukowski foil in a
      Karman vortex street.
AB  - Obstacles and swimming fish in flow create a wake with an alternating left/right
      vortex pattern known as a Karman vortex street and reverse Karman vortex street,
      respectively. An energy-efficient fish behavior resembling slaloming through the
      vortex street is called Karman gaiting. This paper describes the use of a
      bioinspired array of pressure sensors on a Joukowski foil to estimate and control
      flow-relative position in a Karman vortex street using potential flow theory,
      recursive Bayesian filtering, and trajectory-tracking feedback control. The
      Joukowski foil is fixed in downstream position in a flowing water channel and
      free to move on air bearings in the cross-stream direction by controlling its
      angle of attack to generate lift. Inspired by the lateral-line neuromasts found
      in fish, the sensing and control scheme is validated using off-the-shelf pressure
      sensors in an experimental testbed that includes a flapping device to create
      vortices. We derive a potential flow model that describes the flow over a
      Joukowski foil in a Karman vortex street and identify an optimal path through a
      Karman vortex street using empirical observability. The optimally observable
      trajectory is one that passes through each vortex in the street. The estimated
      vorticity and location of the Karman vortex street are used in a closed-loop
      control to track either the optimally observable path or the energetically
      efficient gait exhibited by fish. Results from the closed-loop control
      experiments in the flow tank show that the artificial lateral line in conjunction
      with a potential flow model and Bayesian estimator allow the robot to perform
      fish-like slaloming behavior in a Karman vortex street. This work is a precursor
      to an autonomous robotic fish sensing the wake of another fish and/or performing
      pursuit and schooling behavior.

PMID- 29355110
TI  - Superconducting properties and MUSR study of the noncentrosymmetric
      superconductor Nb0.5Os0.5.
AB  - The properties of the noncentrosymmetric superconductor (alpha-[Formula: see
      text] structure) Nb0.5Os0.5 have been investigated using resistivity,
      magnetization, specific heat, and muon spin relaxation and rotation (MUSR)
      measurements. These measurements suggest that Nb0.5Os0.5 is a weakly coupled
      ([Formula: see text]) type-II superconductor ([Formula: see text]), having a bulk
      superconducting transition temperature T c   =  3.07 K. The specific heat data
      fits well with the single-gap BCS model indicating nodeless s-wave
      superconductivity in Nb0.5Os0.5. The MUSR measurements also confirm [Formula: see
      text]-wave superconductivity with the preserved time-reversal symmetry.

PMID- 29355111
TI  - Dynamics of a quasiparticle in the alpha-T3 model: role of pseudospin
      polarization and transverse magnetic field on zitterbewegung.
AB  - We consider the alpha-T 3 model which provides a smooth crossover between the
      honeycomb lattice with pseudospin 1/2 and the dice lattice with pseudospin 1
      through the variation of a parameter alpha. We study the dynamics of a wave
      packet representing a quasiparticle in the alpha-T3 model with zero and finite
      transverse magnetic field. For zero field, it is shown that the wave packet
      undergoes a transient zitterbewegung (ZB). Various features of ZB depending on
      the initial pseudospin polarization of the wave packet have been revealed. For an
      intermediate value of the parameter alpha i.e. for [Formula: see text] the
      resulting ZB consists of two distinct frequencies when the wave packet was
      located initially in rim site. However, the wave packet exhibits single frequency
      ZB for [Formula: see text] and [Formula: see text]. It is also unveiled that the
      frequency of ZB corresponding to [Formula: see text] gets exactly half of that
      corresponding to the [Formula: see text] case. On the other hand, when the
      initial wave packet was in hub site, the ZB consists of only one frequency for
      all values of alpha. Using stationary phase approximation, we find analytical
      expression of velocity average which can be used to extract the associated
      timescale over which the transient nature of ZB persists. On the contrary, the
      wave packet undergoes permanent ZB in presence of a transverse magnetic field.
      Due to the presence of a large number of Landau energy levels, the oscillations
      in ZB appear to be much more complicated. The oscillation pattern depends
      significantly on the initial pseudospin polarization of the wave packet.
      Furthermore, it is revealed that the number of the frequency components involved
      in ZB depends on the parameter alpha.

PMID- 29355112
TI  - In vitro measurement of platelet adhesion to intact endothelial cells under low
      shear conditions.
AB  - BACKGROUND: Prediction of thrombus formation at intact arterial walls under low
      shear flow conditions is clinically important particularly for better prognoses
      of embolisation in cerebral aneurysms. Although a new mathematical model for this
      purpose is necessary, little quantitative information has been known about
      platelet adhesion to intact endothelial cells. OBJECTIVE: The objective of this
      study is to measure the number of platelets adhering to intact endothelial cells
      with a focus upon the influence of the shear rate. METHODS: Endothelial cells
      disseminated in MU-slides were exposed to swine whole blood at different shear
      rates. Adenosine diphosphate (ADP) was used as an agonist. Adherent platelets
      were counted by means of scanning electron microscopy. RESULTS: At an ADP
      concentration of 1 uM, 20.8 +/- 3.1 platelets per 900 um2 were observed after 30
      minute perfusion at a shear rate of 0.8 s-1 whereas only 3.0 +/- 1.4 per 900 um2
      at 16.8 s-1. CONCLUSIONS: The number of adherent platelets is determined by a
      balance between the shear and the degree of stimulation by the agonist. At an ADP
      concentration of 1 uM, a limit to the shear rate at which platelets can adhere to
      intact endothelial cells is considered to be slightly higher than 16.8 s-1.

PMID- 29355113
TI  - miR-34 increases in vitro PANC-1 cell sensitivity to gemcitabine via targeting
      Slug/PUMA.
AB  - miR-34 was deregulated in tumor tissues compared with corresponding noncancerous
      tissue samples. Furthermore, miR-34 may contribute to cancer-stromal interaction
      associated with cancer progression. However, whether miR-34 could decrease
      chemoresistance of cancer cells to chemotherapeutic agent remains unclear. In our
      study, we examined whether overexpression of miR-34 could sensitize gemcitabine 
      mediated apoptosis in human pancreatic cancer PANC-1 cells. We found that miR-34
      markedly induced gemcitabine -mediated apoptosis in PANC-1 cells. miR-34 induced
      down-regulation of Slug expression and upregulation of p53 up-regulated modulator
      of apoptosis (PUMA) expression. The over-expression of Slug or downregulation of
      PUMA by Slug cDNA or PUMA siRNA transfection markedly blocked miR-34-induced
      gemcitabine sensitization. Furthermore, miR-34 induced PUMA expression by
      downregulation of Slug. Taken together, our study demonstrates that miR-34
      enhances sensitization against gemcitabine-mediated apoptosis through the down
      regulation of Slug expression, and up-regulation of Slug-dependent PUMA
      expression.

PMID- 29355114
TI  - Synergistic role of Caspase-8 and Caspase-3 expressions: Prognostic and
      predictive biomarkers in colorectal cancer.
AB  - BACKGROUND: Expressions of Caspase-8 and Caspase-3 have been identified as
      important markers in many malignant tumors, but their roles in colorectal cancer
      (CRC) have not been confirmed. The purpose of this study was to investigate the
      role of Caspase-8 and Caspase-3 in CRC. METHODS: We enrolled 470 CRC patients in
      this study. Archival paraffin-embedded CRC tissue samples were used to construct
      tissue microarray (TMA), expressions of Caspase-8 and Caspase-3 that were stained
      by immunohistochemistry. Prognostic and predictive role of Caspase-8 and Caspase
      3 expressions, alone or united, were evaluated by univariate and multivariate
      analysis respectively. RESULTS: In comparison with adjacent normal tissues,
      Caspase-8 and Caspase-3 protein levels were upregulated in CRC tissues
      significantly, furthermore, high expressions of Caspase-8 and Caspase-3 were
      correlated with decreased overall survival (OS) (p< 0.05), and also with
      unfavorable clinicopathologic characteristics. Cox regression analysis showed
      that high Caspase-8 and Caspase-3 expressions were independent negative markers
      of OS. CONCLUSION: Caspase-8 and Caspase-3 expressions in tumor tissues are novel
      candidate prognostic markers for CRC patients. It was the first time to be
      identified that Caspase-8 and Caspase-3 expressions had synergistic role as
      efficient prognostic indicators for CRC patients.

PMID- 29355115
TI  - A Clinically-Translatable Machine Learning Algorithm for the Prediction of
      Alzheimer's Disease Conversion in Individuals with Mild and Premild Cognitive
      Impairment.
AB  - BACKGROUND: Available therapies for Alzheimer's disease (AD) can only alleviate
      and delay the advance of symptoms, with the greatest impact eventually achieved
      when provided at an early stage. Thus, early identification of which subjects at
      high risk, e.g., with MCI, will later develop AD is of key importance. Currently
      available machine learning algorithms achieve only limited predictive accuracy or
      they are based on expensive and hard-to-collect information. OBJECTIVE: The
      current study aims to develop an algorithm for a 3-year prediction of conversion
      to AD in MCI and PreMCI subjects based only on non-invasively and effectively
      collectable predictors. METHODS: A dataset of 123 MCI/PreMCI subjects was used to
      train different machine learning techniques. Baseline information regarding
      sociodemographic characteristics, clinical and neuropsychological test scores,
      cardiovascular risk indexes, and a visual rating scale for brain atrophy was used
      to extract 36 predictors. Leave-pair-out-cross-validation was employed as
      validation strategy and a recursive feature elimination procedure was applied to
      identify a relevant subset of predictors. RESULTS: 16 predictors were selected
      from all domains excluding sociodemographic information. The best model resulted
      a support vector machine with radial-basis function kernel (whole sample: AUC =
      0.962, best balanced accuracy = 0.913; MCI sub-group alone: AUC = 0.914, best
      balanced accuracy = 0.874). CONCLUSIONS: Our algorithm shows very high cross
      validated performances that outperform the vast majority of the currently
      available algorithms, and all those which use only non-invasive and effectively
      assessable predictors. Further testing and optimization in independent samples
      will warrant its application in both clinical practice and clinical trials.

PMID- 29355116
TI  - Focusing on employment in primary mental health care: A scoping review.
AB  - BACKGROUND: People with mental health issues usually access primary health care
      services but employment status and/or return to work is not typically an explicit
      focus of a general practice consultation. OBJECTIVE: This scoping review aims to
      investigate the broad range of interventions used in primary health care to
      effectively support people with mental health issues to choose, get, or keep
      employment. METHODS: A literature search was conducted using five electronic
      databases. Peer reviewed research articles published between 1996 and February
      2016 were included in the review. RESULTS: Twelve studies explored work related
      interventions for people with mental health issues in the primary health care
      context. The most commonly used intervention was sickness certification, other
      interventions that show promise were identified but there is limited empirical
      evidence to show their effectiveness in relation to improving employment
      outcomes. General practitioners identified a range of barriers in terms of
      focusing on employment outcomes for patients including knowledge and confidence
      in understanding the impact of work on symptoms and limited access to advice or
      services to refer patients to. CONCLUSIONS: This review suggests that work
      focused interventions situated in primary health care settings appear to be a
      promising approach for people with mental health issues. However, various
      barriers impact the implementation of an employment approach, with limited
      comparisons between different effective interventions. In the context of
      increasing numbers of people presenting with mental health issues, future
      research should address the implementation and effectiveness of work-focused
      interventions based in primary health care.

PMID- 29355117
TI  - Quality evaluation of official accident reports conducted by Labour Authorities
      in Andalusia (Spain).
AB  - BACKGROUND: A public accident investigation is carried out when the consequences
      of the incident are significant or the accident has occurred in unusual
      circumstances. OBJECTIVE: We evaluated the quality of the official accident
      investigations being conducted by Safety Specialists of the Labour Authorities in
      Andalusia. METHODS: To achieve this objective, we analysed 98 occupational
      accident investigations conducted by the Labour Authorities in Andalusia in the
      last quarter of 2014. Various phases in the accident investigation process were
      examined, such as the use of the Eurostat variables within European Statistics on
      Accidents at Work (ESAW), detection of causes, determination of preventive
      measures, cost analysis of the accidents, identification of noncompliance with
      legal requirements or the investigation method used. RESULTS: The results of this
      study show that 77% of the official occupational accident investigation reports
      analysed were conducted in accordance with all the quality criteria recommended
      in the literature. CONCLUSIONS: To enhance glogal learning, and optimize
      allocation of resources, we propose the development of a harmonized European
      model for the public investigation of occupational accidents. Further it would be
      advisable to create a common classification and coding system for the causes of
      accidents for all European Union Member States.

PMID- 29355118
TI  - Should I stay or should I go? A prospective investigation examining individual
      factors impacting employment status among individuals with multiple sclerosis
      (MS).
AB  - BACKGROUND: Rates of unemployment among individuals with multiple sclerosis (MS)
      are as high as 80%. While several factors for such high rates of unemployment
      have been identified, they do not account for the majority of the variance.
      OBJECTIVE: This study examines person-specific factors such as personality and
      coping, which may better account for individuals leaving the workforce. METHOD:
      Forty individuals with MS (20 considering reducing work hours or leaving the
      workforce and 20 remaining employed) were matched on age, gender, education,
      disease duration, and disease course, and administered a comprehensive survey of
      factors purported to be related to employment status. RESULTS: Based on multiple,
      logistic regression analyses certain disease factors and person-specific factors
      differentiate those who are considering leaving work or reducing work hours and
      those staying employed. In particular, those expressing the need to reduce work
      hours or leaving the workforce reported more fatigue, anxiety, depression, and
      use of behavioral disengagement as a means of coping. In contrast, those staying
      employed reported greater levels of extraversion, self-efficacy, and use of humor
      as a means of coping. Together, fatigue, use of humor, and use of behavioral
      disengagement as a means of coping were the most significant factors, accounting
      for 44% of the variance. CONCLUSIONS: Findings suggest that greater consideration
      be given to these factors and that interventions tailored to address these
      factors may assist individuals with MS staying employed and/or making appropriate
      accommodations.

PMID- 29355119
TI  - Comparing two methods to record maximal voluntary contractions and different
      electrode positions in recordings of forearm extensor muscle activity: Refining
      risk assessments for work-related wrist disorders.
AB  - BACKGROUND: Wrist disorders are common in force demanding industrial repetitive
      work. Visual assessment of force demands have a low reliability, instead surface
      electromyography (EMG) may be used as part of a risk assessment for work-related
      wrist disorders. For normalization of EMG recordings, a power grip (hand grip) is
      often used as maximal voluntary contraction (MVC) of the forearm extensor
      muscles. However, the test-retest reproducibility is poor and EMG amplitudes
      exceeding 100% have occasionally been recorded during work. An alternative MVC is
      resisted wrist extension, which may be more reliable. OBJECTIVE: To compare hand
      grip and resisted wrist extension MVCs, in terms of amplitude and
      reproducibility, and to examine the effect of electrode positioning. METHODS:
      Twelve subjects participated. EMG from right forearm extensors, from four
      electrode pairs, was recorded during MVCs, on three separate occasions. RESULTS:
      The group mean EMG amplitudes for resisted wrist extension were 1.2-1.7 times
      greater than those for hand grip. Resisted wrist extension showed better
      reproducibility than hand grip. CONCLUSIONS: The results indicate that the use of
      resisted wrist extension is a more accurate measurement of maximal effort of
      wrist extensor contractions than using hand grip and should increase the
      precision in EMG recordings from forearm extensor muscles, which in turn will
      increase the quality of risk assessments that are based on these.

PMID- 29355121
TI  - Validity and reliability of the Turkish version of the Physical Workload
      Questionnaire.
AB  - BACKGROUND: Although it is necessary to regularly record and assess physical
      workloads in a workplace to prevent work-related musculoskeletal disorders, there
      is no easy to use, valid and reliable questionnaire such as the Physical Workload
      Questionnaire (PWQ) in Turkish. OBJECTIVE: To linguistically and culturally adapt
      the PWQ into Turkish, and to examine the validity and reliability of this adapted
      version. METHODS: One hundred twenty-six participants were recruited. All
      participants filled in the Oswestry Disability Index (ODI) and the Nordic
      Musculoskeletal Questionnaire. To determine test-retest reliability, all
      participants filled in the PWQ after a time interval of one week. RESULTS: There
      was a significant difference in the PWQ indices between the participants with an
      occupation requires less vs. higher workload (p < 0.05). The PWQ index was
      significantly correlated with the proximal musculoskeletal symptoms (rho= 0.301,
      p < 0.05), but not significantly correlated with distal musculoskeletal symptoms
      (rho= 0.121, p > 0.05). The PWQ index was significantly correlated with the ODI
      (rho= 0.193, p < 0.05). The internal consistency of the PWQ was excellent (alpha=
      0.865) and item-total correlations were acceptable. Test-retest reliability was
      high (ICC = 0.865). CONCLUSIONS: The PWQ is the unique valid and reliable
      questionnaire available in Turkish for assessing physical workload due to body
      posture and strenuous effort during work.

PMID- 29355120
TI  - Task rotation in an underground coal mine: A pilot study.
AB  - BACKGROUND: Task rotation is used to decrease the risk of workplace injuries and
      improve work satisfaction. OBJECTIVE: To investigate the feasibility, benefits
      and challenges of implementing a task rotation schedule within an underground
      coalmine in NSW, Australia. METHODS: A mixed method case control pilot study with
      the development and implementation of a task rotation schedule for 6 months with
      two work crews. A questionnaire including The Nordic Musculoskeletal
      Questionnaire, The Need for Recovery after Work Scale, and The Australian WHOQOL-
      BREF Australian Edition was used to survey workers at baseline, 3 and 6 months. A
      focus group was completed with the intervention crew and management at the
      completion of the study. RESULTS: In total, twenty-seven participants completed
      the survey. Significant improvements in the psychological and environmental
      domains of the WHOQOL-BREF questionnaire were found in the intervention crew.
      Musculoskeletal pain was highest in the elbow, lower back and knee, and fatigue
      scores improved, across both groups. The intervention crew felt 'mentally
      fresher', 'didn't do the same task twice in a row', and 'had more task variety
      which made the shift go quickly'. CONCLUSION: Task rotation was positively
      regarded, with psychological benefits identified. Three rotations during a 9-hour
      shift were feasible and practical in this environment.

PMID- 29355122
TI  - Foot placement strategy in pushing and pulling.
AB  - BACKGROUND: Pushing and pulling tasks are very common in daily and industrial
      workplaces. They are one major source of musculoskeletal complaints. OBJECTIVE:
      This study aimed to examine the foot placement strategy while pushing and
      pulling. PARTICIPANTS: Thirteen young males and ten young females were recruited
      as participants. METHODS: A two (pushing and pulling) by four (48 cm, 84 cm, 120
      cm, and 156 cm) factorial design was used. RESULTS: Exertion direction and
      exertion height significantly affected foot placement strategy. Pushing task
      needed more anteroposterior space than pulling task. The percentages of
      female/male for trailing foot position ranged from 77% to 90% (pushing) and from
      80% to 93% (pulling) across the exertion heights. CONCLUSION: Practitioners
      should provide an anteroposterior space approximately to 70% body stature for
      workers to exert their maximum pulling and pushing strengths.

PMID- 29355123
TI  - Mental disorder sick leave in Sweden: A population study.
AB  - BACKGROUND: The inability to perform productive work due to mental disorders is a
      growing concern in advanced societies. OBJECTIVE: To investigate medically
      certified mental disorder and all-cause sick leave in a working population using
      demographic, socioeconomic and occupational predictors. METHODS: The study
      population was the entire Swedish work force aged 16-64 years in December 31st
      2011. The outcome was sick leave exceeding 14 days in 2012 with adjustment for 13
      confounders. RESULTS: The risk of sick leave with a mental disorder is higher
      among women compared to men, among persons aged 30-39 and among parents in
      families with underage children. Employees in welfare service occupations within
      health care, education and social services have an elevated risk of mental
      disorder sick leave and constitute a large proportion of the workforce.
      CONCLUSION: The results support the need for improving early detection and
      prevention of mental disorders in the workforce. Improvements in psychosocial
      work environments are essential, where the higher risk in female dominated
      welfare occupations particularly, have repercussions on the quality of the
      welfare services provided for vulnerable groups in society. Better work-life
      balance in families with younger children could also mitigate the effects of a
      high total workload in that particular phase of life.

PMID- 29355124
TI  - Employed and expecting in Germany: A qualitative investigation into pregnancy
      related occupational stress and coping behavior.
AB  - BACKGROUND: Previous studies demonstrate a higher risk for pregnant women to
      experience stressors within the work context and therefore suggest a higher risk
      for occupational stress. However, the interaction between work and pregnancy in
      Germany is currently an area without much active research, even though it is a
      common occurrence. OBJECTIVE: This qualitative study explores stressors, coping
      behaviors and related consequences for pregnant employees in Germany.
      Furthermore, the study researches intervention possibilities for the purpose to
      prevent the target group from negative health outcomes. METHODS: Thirteen semi
      standardized interviews with employed pregnant women living and working in
      Germany were conducted. The interviews were recorded and verbatim transcribed.
      Data was analyzed by Mayring's structuring qualitative content analysis. RESULTS:
      Compounding the results, the interviewed women noted most frequently stressors in
      relation to their employer/line manager due to their pregnant condition. Even
      though the women showed various adaptive coping behaviors, the identified
      negative consequences, mainly on their emotional wellbeing. Various intervention
      possibilities to improve the pregnant employee's situation were mentioned.
      CONCLUSIONS: This study was able to explore broad insights into the topic of
      pregnant employees in Germany. Therefore, this study underlines the actuality and
      relevance of the topic and is able to contribute to a scientific discussion about
      pregnancy at the workplace.

PMID- 29355125
TI  - The experiences and perceptions of persons with disabilities regarding work
      skills development in sheltered and protective workshops.
AB  - BACKGROUND: Protective workshops and sheltered employment settings have been
      instrumental in developing the work skills of people with disabilities, however
      there has been a void in the literature about its influence on the ability of
      individuals to find employment in the open labor market. OBJECTIVE: The aim of
      the study is to explore the experiences and perceptions of people with
      disabilities about the development of their work skills for transitioning into
      the open labor market. PARTICIPANTS: Five individuals with various types of
      disabilities and two key informants participated in the study. METHODS: The
      research study was positioned within the qualitative paradigm specifically
      utilizing an exploratory and descriptive research design. In order to gather data
      from the participants, semi structured interviews were used. RESULTS: Three
      themes emerged from the findings of the study. Theme one, designated as "Reaching
      a ceiling", reflected the barriers that the participants experienced regarding
      work skills development. Theme two, designated as "Enablers for growth within the
      workplace", related to the enabling factors related to development of the work
      skills of persons with a disability (PWD). The final theme related to the meaning
      that PWD associated to their worker role and was designated as "A sense of
      universality". CONCLUSION: The participants highlighted that they felt their
      coworkers in the workshops were "like family" to them and thoroughly enjoyed the
      work tasks and work environment, expressing specific support from their fellow
      workers. Through reaching their goals, engaging in their work tasks and having
      the sense of universality in the workplace, the workers felt that the work they
      participated in gave them meaning to their life. The findings of the study
      indicated that managers of protective workshops and sheltered employment settings
      should consider selecting work tasks that enable the development of skills needed
      in the open labour market. A work skills development system whereby PWD in these
      workshops could determine their own career progression is advocated.

PMID- 29355126
TI  - Lessons learned from women in leadership positions.
AB  - BACKGROUND: Eileen Elias has decades of experience in leadership positions within
      government and nongovernmental organizations. As the first female Commissioner
      for Mental Health in the Commonwealth of Massachusetts and the US in the early
      1990s, Elias gained experience on navigating gender-based challenges to attain
      recognized performance outcomes. OBJECTIVE: From lessons learned from women
      leaders, educate young women entering their careers on attaining leadership
      positions. METHODS: Comprehensive research of literature from 2012 through 2017
      and interviews with women leaders representing non-Fortune 500 companies
      including academia, research, non-profit, for-profit, and primary and secondary
      education. Interviewees included:1.Gail Bassin, Co-Chief Executive Officer and
      Treasurer, JBS International Inc.2.Jeri Epstein, Executive Director, The Ambit
      Foundation3.Valerie Fletcher, Executive Director, Institute for Human Centered
      Design4.Christine James-Brown, President and CEO, Child Welfare League of
      America5.Daria Mochly-Rosen, PhD, Professor and Fellow, Chemical and Systems
      Biology, Stanford University School of Medicine6.Eileen O'Keefe, MD, MPH,
      Clinical Associate Professor and Director, Boston University Health
      Sciences7.Jeri Shaw, President and Co-Chief Executive Officer, JBS International
      Inc. RESULTS/CONCLUSIONS: A comprehensive understanding of key women leaders'
      lessons learned and recommendations targeting young women as they assess
      leadership opportunities in the public or private sectors.

PMID- 29355127
TI  - Bringing a structural perspective to work: Framing occupational safety and health
      disparities for nursing assistants with work-related musculoskeletal disorders.
AB  - BACKGROUND: Certified Nursing Assistants (CNAs) experience a high risk of work
      related musculoskeletal disorders (WMSDs) and are further made vulnerable by
      their situation in low levels of workplace and societal hierarchies of power and
      privilege. OBJECTIVE: This study applies structural vulnerability theory to CNA
      WMSD experiences in order to identify structural factors that may influence such
      injuries. METHODS: A sample of CNAs (n = 26) working in Nursing and Residential
      Care Facilities (NRCFs) was selected from workers who filed a claim during 2011
      2014 for a WMSD of the back, shoulder, knee, or hand/wrist in the Washington
      State Department of Labor & Industries workers' compensation system. Interviews
      included questions about workers' injury experiences and work contexts.
      Qualitative data was analyzed for themes related to structural vulnerability
      theory and occupational safety and health (OSH) models. RESULTS: Themes
      illustrate a work environment in NRCFs with major organizational deficiencies for
      CNA safety and a broader structural environment that appears to mediate them.
      CNAs described policies and practices that result from management priorities
      being diverted away from worker safety. These difficulties are compounded by
      several aspects of CNAs' socio-economic vulnerability. CONCLUSIONS: This study
      demonstrates the utility of a structural perspective for OSH disparities research
      and points to the need for occupational health intervention on a structural
      level.

PMID- 29355128
TI  - The effect of load on biomechanics of the back and upper limb in a bench to
      shoulder lift during the WorkHab Functional Capacity Evaluation.
AB  - BACKGROUND: Limited literature exists investigating biomechanical changes during
      a Functional Capacity Evaluation (FCE). OBJECTIVE: To determine change in joint
      angle measurement between minimum load to safe maximum load in the bench to
      shoulder lift of the WorkHab FCE. METHODS: Dartfish ProSuite was used to analyse
      bench to shoulder lift video from 28 subjects. Measurements of joint angle at
      lumbar spine, thoracic spine, elbow and shoulder at four points in the ascending
      and descending lift phases (0/3, 1/3, 2/3, 3/3) in the minimum load and safe
      maximum lift were collected. Paired t-tests were used to analyse differences in
      joint angles between lifts. RESULTS: Significant differences in joint angles were
      identified in the thoracic spine, elbow and shoulder at maximal weight. Increased
      extension occurred: Thoracic spine at 3/3 ascending [2.922, 95% CI 0.8, 3.8, p =
      0.004]. Increased flexion occurred: elbow ascending [1/3:6.405, 95% CI -11.8,
      1.8, p = 0.008],[3/3:15.575, 95% CI 4.2, 27.0, p = 0.009]; elbow descending
      [0/3:18.446, 95% CI 9.5, 27.4, p = 0.000]; shoulder ascending [3/3:16.785, 95% CI
      11.8, 21.8, p < 0.001]; shoulder descending [0/3:16.647, 95% CI 10.6, 22.7, p <
      0.001]. CONCLUSIONS: This study provides insight into the biomechanical changes
      during a bench to shoulder lift and support observations and clinical reasoning
      used in determining the safe maximal lift.

PMID- 29355129
TI  - A scoping review on smart mobile devices and physical strain.
AB  - BACKGROUND: Smart mobile devices gain increasing importance at work. Integrating
      these smart mobile devices into the workplace creates new opportunities and
      challenges for occupational health and safety. OBJECTIVES: Therefore the aim of
      the following scoping review was to identify ergonomic challenges with the use of
      smart mobile devices at work with respect to physical problems. METHOD: A review
      of 36 papers based on literature including January 2016 was conducted. RESULTS:
      Biomechanical measures in the reviewed studies demonstrated i.e., head flexion
      angles exceeding 20 degrees  in 20 out of 26 different conditions described.
      Furthermore, laterally deviated wrists were frequently noted and thumb and finger
      flexor muscle activities generally greater than 5% MVC were reported. CONCLUSION:
      The reviewed literature indicated an elevated biomechanical risk, especially for
      the neck, the wrists and thumb. This was due to poor posture, ongoing and
      intermitted muscle tension, and/or repetitive movements. Papers addressing
      specific risks for smartphone and tablet use in different work environments are
      scarce. As the technology, as well as the use of smart mobile devices is rapidly
      changing, further research, especially for prolonged periods in the workplace is
      needed.

PMID- 29355132
TI  - Using motion capture technology to measure the effects of magnification loupes on
      dental operator posture: A pilot study.
AB  - BACKGROUND: Motion analysis has great potential for quantitatively evaluating
      dental operator posture and the impact of interventions such as magnification
      loupes on posture and subsequent development of musculoskeletal disorders.
      OBJECTIVE: This study sought to determine the feasibility of motion capture
      technology for measurement of dental operator posture and examine the impact that
      different styles of magnification loupes had on dental operator posture. METHODS:
      Forward and lateral head flexion were measured for two different operators while
      completing a periodontal probing procedure. Each was measured while wearing
      magnification loupes (flip up-FL and through the lens-TTL) and basic safety
      lenses. RESULTS: Operators both exhibited reduced forward flexion range of motion
      (ROM) when using loupes (TTL or FL) compared to a baseline lens (BL). In contrast
      to forward flexion, no consistent trends were observed for lateral flexion
      between subjects. CONCLUSIONS: The researchers can report that it is possible to
      measure dental operator posture using motion capture technology. More study is
      needed to determine which type of magnification loupes (FL or TTL) are superior
      in improving dental operator posture. Some evidence was found supporting that the
      quality of operator posture may more likely be related to the use of
      magnification loupes, rather than the specific type of lenses worn.

PMID- 29355130
TI  - Strategies of employees in the construction industry to increase their
      sustainable employability.
AB  - BACKGROUND: The aging work force makes sustainable employability (SE) of workers
      a priority. However, it is unknown to what extent employees use implemented SE
      measures. OBJECTIVE: To determine the utilization of 1) SE measures offered by
      employers, 2) employee SE strategies, and 3) to identify barriers and
      facilitators of SE strategies. METHODS: Survey data were collected among 731 blue
      collar and 879 white collar workers to determine the utilization of employer SE
      measures. Focus groups were held with 16 blue collar and 17 white collar workers
      to identify employee SE strategies and their barriers and facilitators. RESULTS:
      Utilization of employer SE measures was highest for personal development
      measures. Strategies applied by blue collar workers included using equipment,
      suggesting improvements of their working conditions, and seeking promotion to a
      less physically demanding job. White collar workers named engaging in leisure
      time physical activity and seeking an adequate work-life balance. Implementation
      of these strategies was influenced by employee awareness and self-efficacy, the
      accessibility and costs and benefits of the strategy, management support and
      company culture. CONCLUSION: Usage of employer SE measures was generally low and
      recommendations are given for both blue and white collar workers to improve SE
      strategies.

PMID- 29355133
TI  - Atherosclerosis & ischaemic heart disease: Here to stay or gone tomorrow.

PMID- 29355134
TI  - Molecular interphase between extracellular matrix & cancer cells.

PMID- 29355135
TI  - Shorter & cheaper regimen to treat multidrug-resistant tuberculosis: A new hope.

PMID- 29355136
TI  - Evolution of technology for molecular genotyping in blood group systems.
AB  - The molecular basis of the blood group antigens was identified first in the 1980s
      and 1990s. Since then the importance of molecular biology in transfusion medicine
      has been described extensively by several investigators. Molecular genotyping of
      blood group antigens is one of the important aspects and is successfully making
      its way into transfusion medicine. Low-, medium- and high-throughput techniques
      have been developed for this purpose. Depending on the requirement of the centre
      like screening for high- or low-prevalence antigens where antisera are not
      available, correct typing of multiple transfused patients, screening for antigen
      negative donor units to reduce the rate of alloimmunization, etc. a suitable
      technique can be selected. The present review discusses the evolution of
      different techniques to detect molecular genotypes of blood group systems and how
      these approaches can be used in transfusion medicine where haemagglutination is
      of limited value. Currently, this technology is being used in only a few blood
      banks in India. Hence, there is a need for understanding this technology with all
      its variations.

PMID- 29355138
TI  - Management of malaria in pregnancy.
AB  - Pregnant women are especially susceptible to malaria infection. Without existing
      immunity, severe malaria can develop requiring emergency treatment, and pregnancy
      loss is common. In semi-immune women, consequences of malaria for the mother
      include anaemia while stillbirth, premature delivery and foetal growth
      restriction affect the developing foetus. Preventive measures include insecticide
      treated nets and (in some African settings) intermittent preventive treatment.
      Prompt management of maternal infection is key, using parenteral artemisinins for
      severe malaria, and artemisinin combination treatments (ACTs) in the second and
      third trimesters of pregnancy. ACTs may soon also be recommended as an
      alternative to quinine as a treatment in the first trimester of pregnancy.
      Monitoring the safety of antimalarials and understanding their pharmacokinetics
      is particularly important in pregnancy with the altered maternal physiology and
      the risks to the developing foetus. As increasing numbers of countries embrace
      malaria elimination as a goal, the special needs of the vulnerable group of
      pregnant women and their infants should not be overlooked.

PMID- 29355137
TI  - Interplay of cytokines in preterm birth.
AB  - Preterm infants (i.e., born before <37 wk of gestation) are at increased risk of
      morbidity and mortality and long-term disabilities. Global prevalence of preterm
      birth (PTB) varies from 5 to 18 per cent. There are multiple aetiological causes
      and factors associated with PTB. Intrapartum infections are conventionally
      associated with PTB. However, maternal genotype modulates response to these
      infections. This review highlights the association of cytokine gene polymorphisms
      and their levels with PTB. Varying PTB rates across the different ethnic groups
      may be as a result of genetically mediated varying cytokines response to
      infections. Studies on genetic variations in tumour necrosis factor-alpha,
      interleukin-1 alpha (IL-1alpha), IL-1beta, IL-6, IL-10 and toll-like receptor-4
      genes and their association with PTB, have been reviewed. No single polymorphism
      of the studied genes was found to be associated with PTB. However, increased
      maternal levels of IL-1beta and IL-6 and low levels of IL-10 have been found to
      be associated with PTB.

PMID- 29355139
TI  - Prognostic significance of plasma matrix metalloprotease-2 in pancreatic cancer
      patients.
AB  - BACKGROUND & OBJECTIVES: Pancreatic cancer has a propensity for wide stromal
      invasion. Matrix metalloprotease-2 (MMP-2) is a protease that degrades the peri
      tumoural tissue and helps in tumour dissemination. Thus, this study was aimed to
      assess any association of plasma MMP-2 levels with clinicopathological parameters
      and survival of patients with pancreatic cancer. METHODS: Plasma samples from 127
      pancreatic cancer patients were analyzed for MMP-2 levels by ELISA. Survival and
      other clinicopathological parameters of patients were analyzed for any
      correlation with plasma MMP-2 levels. RESULTS: The mean MMP-2 levels in
      pancreatic cancer patients were 560.3+/-222.0 ng/ml which were significantly
      elevated compared to chronic pancreatitis patients (P<0.001) and healthy
      individuals (P<0.05). The plasma levels of MMP-2 significantly correlated with
      tissue expression of this protease (P=0.004). However, MMP-2 levels did not
      exhibit any association either with clinicopathological parameters or with
      survival. INTERPRETATION & CONCLUSIONS: Elevated MMP-2 levels were observed in
      blood of pancreatic cancer patients which correlated with its tissue expression.
      However, these levels did not associate with survival or any clinicopathological
      parameters of patients. Further studies need to be done to confirm the
      prognostic/ clinical significance of MMP-2 in cancer patients before and after
      surgery.

PMID- 29355140
TI  - Impact of embryo co-culture with cumulus cells on pregnancy & implantation rate
      in patients undergoing in vitro fertilization using donor oocyte.
AB  - BACKGROUND & OBJECTIVES: Cumulus cell co-culture of embryo had been found to be
      beneficial for achieving better pregnancy and implantation rate (IR). The present
      study was aimed to evaluate efficiency of cumulus co-culture technique over
      simple culture of embryo in terms of pregnancy rate (PR) and IR in patients
      undergoing treatment for infertility using donor oocytes fertilized by
      intracytoplasmic sperm injection. METHODS: This was a quasi-experimental study
      between control and study groups. The primary endpoint was achievement of
      pregnancy. Control group included 508 women who underwent embryo development
      without cumulus cell co-culture and study group included 394 women who underwent
      embryo development with cumulus cell co-culture using donor's cumulus cells.
      RESULTS: The present study demonstrated a significant increase in the IR (37.2 vs
      24.2%, P<0.001) and in PR (45.7 vs 37.8%, P<0.05) in study group than in control
      group. The PR and IR were found to be higher in study group, among all groups of
      women, grouped on the basis of different indications for use of donor oocytes.
      INTERPRETATION & CONCLUSIONS: Cumulus cell co-culture technique was found to be
      more effective than simple culture technique for embryo development in women
      undergoing treatment for infertility using donor oocytes fertilized by
      intracytoplasmic sperm injection.

PMID- 29355141
TI  - An observational study of incidence, risk factors & outcome of systemic
      inflammatory response & organ dysfunction following major trauma.
AB  - BACKGROUND & OBJECTIVES: Trauma is known to lead to systemic inflammatory
      response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), which is
      often a cause of late deaths after injury. SIRS and MODS have been objectively
      measured using scoring systems. This prospective observational study was carried
      out in a tertiary care hospital in India to evaluate SIRS and MODS following
      trauma in terms of their incidence, the associated risk factors and the effect on
      the outcome. METHODS: All adult patients with major life- and limb-threatening
      trauma were included. Patients who died within 24 h, those with severe head
      injury, known comorbidity, immunocompromised state, on immunosuppressants or
      pregnancy were excluded. SIRS and MODS scores were recorded after initial
      management (baseline score), on days 3 and 6 of admission. SIRS was defined as
      SIRS score of >=2 and MODS was defined as MODS score of >=1. RESULTS: Two hundred
      patients were enrolled. SIRS was noted in 156 patients (78%). MODS was noted in
      145 (72.5%) patients. Overall mortality was 39 (19.5%). Both SIRS and MODS scores
      were significantly associated with age >60 yr, blunt injury, (lower) revised
      trauma score hypotension on admission and (higher) injury severity score, but not
      with gender, pre-hospital time or operative treatment. INTERPRETATION &
      CONCLUSIONS: Both SIRS and MODS scores were associated with longer Intensive Care
      Unit (ICU) stay, more ICU interventions and higher mortality. Incidence of MODS
      was significantly higher in patients with SIRS. Both scores showed rising trend
      with time in non-survivors and a decreasing trend in survivors. The serial
      assessment of scores can help prognosticate outcome and also allocate appropriate
      critical care resources to patients with rising scores.

PMID- 29355142
TI  - Cost of delivering secondary-level health care services through public sector
      district hospitals in India.
AB  - BACKGROUND & OBJECTIVES: Despite an impetus for strengthening public sector
      district hospitals for provision of secondary health care in India, there is lack
      of robust evidence on cost of services provided through these district hospitals.
      In this study, an attempt was made to determine the unit cost of an outpatient
      visit consultation, inpatient bed-day of hospitalization, surgical procedure and
      overall per-capita cost of providing secondary care through district hospitals.
      METHODS: Economic costing of five randomly selected district hospitals in two
      north Indian States - Haryana and Punjab, was undertaken. Cost analysis was done
      using a health system perspective and employing bottom-up costing methodology.
      Quantity of all resources - capital or recurrent, used for delivering services
      was measured and valued. Median unit costs were estimated along with their 95 per
      cent confidence intervals. Sensitivity analysis was undertaken to assess the
      effect of uncertainties in prices and other assumptions; and to generalize the
      findings for Indian set-up. RESULTS: The overall annual cost of delivering
      secondary-level health care services through a public sector district hospital in
      north India was ' 11,44,13,282 [US Dollars (USD) 2,103,185]. Human resources
      accounted for 53 per cent of the overall cost. The unit cost of an inpatient bed
      day, surgical procedure and outpatient consultation was ' 844 (USD 15.5), ' 3481
      (USD 64) and ' 170 (USD 3.1), respectively. With the current set of resource
      allocation, per-capita cost of providing health care through district hospitals
      in north India was ' 139 (USD 2.5). INTERPRETATION & CONCLUSIONS: The estimates
      obtained in our study can be used for Fiscal planning of scaling up secondary
      level health services. Further, these may be particularly useful for future
      research such as benefit-incidence analysis, cost-effectiveness analysis and
      national health accounts including disease-specific accounts in India.

PMID- 29355143
TI  - Value of CD16/CD66b/CD45 in comparison to CD55/CD59/CD45 in diagnosis of
      paroxysmal nocturnal haemoglobinuria: An Indian experience.
AB  - BACKGROUND & OBJECTIVES: Diagnosis of paroxysmal nocturnal haemoglobinuria (PNH),
      a rare haematopoietic stem cell disorder, is challenging in patients with bone
      marrow failure (BMF) syndrome like aplastic anaemia (AA). This study was
      conducted with the aim to test the efficacy of the newly recommended markers viz.
      anti-CD16 and CD66b antibody over the existing anti-CD55 and CD59 antibody for
      PNH diagnosis in India. METHODS: This study was conducted on 193 suspected cases
      of PNH by flow cytometry using lyse wash technique to stain the granulocytes with
      CD16/CD66b and CD55/CD59. RESULTS: Of the 193 suspected cases, 62 patients showed
      the presence of PNH clone. Forty six patients were detected by CD55/CD59/CD45,
      whereas 61 were detected by CD16/CD66b/CD45. CD16/CD66b detected 16 (25.8%)
      additional patients over CD55/CD59 (P<0.05) and was more sensitive in detecting
      the PNH clone with higher negative predictive value. Most of the patients (11/16)
      who were picked up by CD16/CD66b were of AA who had small clone sizes. Further,
      the PNH clones were more discreetly identified in CD16/CD66b plots than by
      CD55/CD59. Clone size assessed by CD16/CD66b which reflects the clinical severity
      of classical PNH (thrombosis/haemolysis), was more representative of the
      underlying clinical condition than CD55/59. INTERPRETATION & CONCLUSIONS: In our
      experience of 62 patients of PNH, CD16/CD66b proved to be more efficacious in
      detecting PNH. The new panel was especially useful in monitoring PNH associated
      with BMF which had small clone sizes.

PMID- 29355144
TI  - Ethyl pyruvate improves skin flap survival after ischaemia reperfusion injury.
AB  - BACKGROUND & OBJECTIVES: Reperfusion after ischaemia is detrimental to the
      tissues. The oxidative stress created and cytokines released are mostly
      responsible in this process. In this study, ethyl pyruvate, a known agent for its
      anti-inflammatory and antioxidant properties, was used to investigate the effects
      on ischaemia/reperfusion injury on skin island flaps in rats. METHODS: Sixty rats
      were randomly distributed in three groups (non-ischaemic, ischaemic and
      medication groups). Ethyl pyruvate was administered in the medication group with
      a dose of 50 mg/kg. After 24 h and one week, the animals were sacrificed, and the
      flaps were analyzed macroscopically, histopathologically, biochemically (total
      nitrite, malondialdehyde and myeloperoxidase). RESULTS: Biochemical markers
      indicating oxidative stress, were found elevated in ischaemic group, whereas
      medication with ethyl pyruvate significantly reduced these values. There was a
      significant reduction (P<0.05) in the levels of these markers between ischaemic
      and medication groups. Ethyl pyruvate improved all the parameters significantly.
      INTERPRETATION & CONCLUSION: Ethyl pyruvate showed strong scavenger activity
      against reactive oxygen species. It could be a potential candidate to improve the
      flap viability in reconstructive microsurgery, especially in free tissue
      transfers. However, more studies are warranted in experimental models to confirm
      these findings.

PMID- 29355145
TI  - Molecular characterization of Plasmodium falciparum in Arunachal Pradesh from
      Northeast India based on merozoite surface protein 1 & glutamate-rich protein.
AB  - BACKGROUND & OBJECTIVES: Northeast (NE) India is one of the high endemic regions
      for malaria with a preponderance of Plasmodium falciparum, resulting in high
      morbidity and mortality. The P. falciparum parasite of this region showed high
      polymorphism in drug-resistant molecular biomarkers. However, there is a paucity
      of information related to merozoite surface protein 1 (msp-1) and glutamate-rich
      protein (glurp) which have been extensively studied in various parts of the
      world. The present study was, therefore, aimed at investigating the genetic
      diversity of P. falciparum based on msp-1 and glurp in Arunachal Pradesh, a State
      in NE India. METHODS: Two hundred and forty nine patients with fever were
      screened for malaria, of whom 75 were positive for P. falciparum. Blood samples
      were collected from each microscopically confirmed patient. The DNA was
      extracted; nested polymerase chain reaction and sequencing were performed to
      study the genetic diversity of msp-1 (block 2) and glurp. RESULTS: The block 2 of
      msp-1 gene was found to be highly polymorphic, and overall allelic distribution
      showed that RO33 was the dominant allele (63%), followed by MAD20 (29%) and K1
      (8%) alleles. However, an extensive diversity (9 alleles and 4 genotypes) and 6
      10 repeat regions exclusively of R2 type were observed in glurp. INTERPRETATION &
      CONCLUSIONS: The P. falciparum population of NE India was diverse which might be
      responsible for higher plasticity leading to the survival of the parasite and in
      turn to the higher endemicity of falciparum malaria of this region.

PMID- 29355146
TI  - Development & standardization of an in-house IgM indirect ELISA for the detection
      of parvovirus B19 infections.
AB  - BACKGROUND & OBJECTIVES: Parvovirus B19 infections occur worldwide; the infection
      is acquired early in childhood but could occur later. B19 is reported to cause
      infection in childhood febrile illnesses, and arthropathies in adults and
      children and in end-stage renal disease (ESRD) seen in adults. This study was
      designed to develop an in-house IgM indirect ELISA for serological screening
      among patients and controls, and to compare ELISA results with those of nested
      polymerase chain reaction (nPCR) assay. METHODS: An in-house IgM indirect ELISA
      was standardized using peptide sequence of VP1/VP2 region of parvovirus B19. A
      total of 201 children and adult with febrile illnesses, 216 individuals with non
      traumatic arthropathies, 201 cases of chronic anaemia associated with ESRD and
      100 healthy controls were tested. Serum was separated from the blood and
      subsequently used for DNA extraction. The nested polymerase chain reaction (nPCR)
      for the detection of B19V DNA was performed using primers targeting the
      overlapping region of VP1/VP2 capsid protein genes. RESULTS: A total of 618
      samples were tested for parvovirus B19 by an in-house IgM indirect ELISA. Among
      these samples, six were positive by in-house ELISA. The inter-rater agreement
      between ELISA and PCR assays was calculated using kappa coefficient analysis. The
      value of kappa was 0.77 and the strength of agreement was 'good' (P<0.001).
      INTERPRETATION & CONCLUSIONS: The in-house IgM indirect ELISA was found to be
      simple with high sensitivity and specificity when compared with nPCR and could be
      used as an alternative to expensive commercial kits in resource-poor settings.

PMID- 29355148
TI  - Multiplex polymerase chain reaction of genetic markers for detection of
      potentially pathogenic environmental Legionella pneumophila isolates.
AB  - BACKGROUND & OBJECTIVES: Genomic constitution of the bacterium Legionella
      pneumophila plays an important role in providing them a pathogenic potential.
      Here, we report the standardization and application of multiplex polymerase chain
      reaction (PCR) for the detection of molecular markers of pathogenic potential in
      L. pneumophila in hospital environment. METHODS: Culture of the standard strains
      of L. pneumophila was performed in buffered charcoal-yeast extract agar with L
      cysteine at p H 6.9. Primers were designed for multiplex PCR, and standardization
      for the detection of five markers annotated to L. pneumophila plasmid pLPP
      (11A2), lipopolysaccharide synthesis (19H4), CMP-N-acetylneuraminic acid
      synthetase (10B12), conjugative coupling factor (24B1) and hypothetical protein
      (8D6) was done. A total of 195 water samples and 200 swabs were collected from
      the hospital environment. The bacterium was isolated from the hospital
      environment by culture and confirmed by 16S rRNA gene PCR and restriction enzyme
      analysis. A total of 45 L. pneumophila isolates were studied using the
      standardized multiplex PCR. RESULTS: The PCR was sensitive to detect 0.1 ng/MUl
      DNA and specific for the two standard strains used in the study. Of the 45
      hospital isolates tested, 11 isolates had four markers, 12 isolates had three
      markers, 10 isolates had two markers, nine isolates had one marker and three
      isolates had none of the markers. None of the isolates had all the five markers.
      INTERPRETATION & CONCLUSIONS: The findings of this study showed the presence of
      gene markers of pathogenic potential of the bacterium L. pneumophila. However,
      the genomic constitution of the environmental isolates should be correlated with
      clinical isolates to prove their pathogenic potential. Rapid diagnostic methods
      such as multiplex PCR reported here, for elucidating gene markers, could help in
      future epidemiological studies of bacterium L. pneumophila.

PMID- 29355147
TI  - Unreliability of three commercial Coxiella burnetii phase II IgM ELISA kits for
      the seroscreening of acute Q fever in human cases.
AB  - BACKGROUND & OBJECTIVES: Seroprevalence of Q fever (QF) caused by Coxiella
      burnetii has been reported from different parts of India. Usually
      serological/molecular tests are employed for detection of infection. The present
      study was undertaken to verify the validity of three different QF phase II IgM
      ELISA kits for acute QF diagnosis by comparing with the gold standard indirect
      fluorescent antibody assay (IFA). METHODS: Fifty eight serum samples collected
      from 42 patients (26 patients provided acute sample only and 16 both acute and
      convalescent samples) which were examined by all three commercial kits, were
      cross-checked with QF Phase II IgM IFA for confirmation. RESULTS: Eleven patients
      were positive for C. burnetii antibodies by IFA in acute and/or convalescent
      serum samples. Taking IFA as a reference, percentages of sensitivity,
      specificity, positive predictive value and negative predictive value for Virion
      Serion/Vircell/NovaTec were 36.36, 61.29, 25.00, 73.08; 81.82, 35.48, 31.03,
      84.62 and 100, 25.81, 32.35, 100 per cent, respectively. INTERPRETATION &
      CONCLUSIONS: The three different ELISA kits exhibited poor agreement amongst them
      and unacceptable level of false positivity. IFA remains to be the only option for
      diagnosing acute QF. Discrepancy between the clinical findings and IFA/ELISA
      results needs confirmation by C. burnetii DNA detection in real-time polymerase
      chain reaction.

PMID- 29355150
TI  - Evaluation of casein & whey protein hydrolysates as well as milk fermentates from
      Lactobacillus helveticus for expression of gut hormones.
AB  - BACKGROUND & OBJECTIVES: Milk proteins play a beneficial role in the regulation
      of food intake, postprandial glycaemia and enteroendocrine hormone secretions and
      thus are receiving considerable attention for the management of metabolic
      inflammatory disorders such as type 2 diabetes mellitus (T2DM). The objective of
      this study was to evaluate the efficacy of peptide/s obtained from milk proteins
      (casein and whey) as well as from the milk fermented with Lactobacillus
      helveticus as secretagogues for gut hormones and to purify and characterize the
      active peptides. METHODS: Effect of hydrolysates of casein protein (CP) and whey
      protein (WP) and L. helveticus fermented milk on the expression of proglucagon,
      pro-gastric inhibitory peptide (GIP) and cholecystokinin (CCK) genes was
      monitored by real-time quantitative polymerase chain reaction. The active
      glucagon-like peptide-1 (GLP-1) secretion was also quantitatively measured using
      ELISA. RESULTS: Hydrolysates of CP and WP as well as fermentates of L. helveticus
      induced the proglucagon, pro-GIP and CCK expression and secretion of GLP-1 in STC
      1 (pGIP/Neo) cells. However, intact casein exhibited maximum GLP-1 secretion and
      proglucagon expression. Two active peptides (F5 and F7) derived from CP1 and WP3
      hydrolysates having the ability to upregulate the GLP-1 secretion by 1.6 and 1.8
      folds were obtained, and the mass was found to be 786 and 824 Da, respectively,
      as determined by electrospray ionization-mass spectrometry. However, no single
      active peptide from L. helveticus fermented milk could be obtained.
      INTERPRETATION & CONCLUSIONS: Casein as well as fermentates obtained from L.
      helveticus fermented milk showed higher potential for GLP-1 induction. These can
      be explored as novel therapeutics to T2DM effectively after demonstrating their
      in vivo efficacy in appropriate animal models.

PMID- 29355149
TI  - Prevalence of Vibrio cholerae O1 serogroup in Assam, India: A hospital-based
      study.
AB  - BACKGROUND & OBJECTIVES: Although cholera remains to be an important public
      health problem, studies on reliable population-based estimates of laboratory
      confirmed cholera in endemic areas are limited worldwide. The aim of this
      hospital-based study was to evaluate the prevalence of Vibrio cholerae serogroup
      in Assam, India, during 2003-2013. METHODS: Stool samples/rectal swabs were
      collected from acute watery diarrhoea (AWD) cases during 2003-2013 and processed
      by standard microbiological procedures. Antibiotic sensitivity test was done
      following the Clinical and Laboratory Standards Institute guidelines. Year-wise
      epidemiological trend of cholera was analyzed. RESULTS: Cholera contributed to
      3.93 per cent of AWD cases. In Assam, cholera was found to be more prevalent in
      the rural areas (6.7%) followed by the tea gardens (5.06%), urban slum (1.9%) and
      urban areas (1.4%). Highest proportion of cholera (13.7%) was observed in 0-10 yr
      age group. Of them, 11.5 per cent belonged to 0-5 yr age group. V. cholerae O1 El
      Tor serotype Ogawa was the predominant isolate. Multiple drug-resistant isolates
      of V. cholerae O1 Ogawa were reported in the study. INTERPRETATION & CONCLUSIONS:
      Emergence of resistance amongst V. cholerae towards many antibiotics is a matter
      of concern. Hence, continuous surveillance for diarrhoeal disorders is necessary
      to control the future outbreaks of cholera in this region.

PMID- 29355151
TI  - Staphylococcus hominis subsp. novobiosepticus, an emerging multidrug-resistant
      bacterium, as a causative agent of septicaemia in cancer patients.
AB  - Staphylococcus hominis subsp. novobiosepticus is a new sub-species of S. hominis,
      thus dividing S. hominis into subsp. hominis and novobiosepticus. This study was
      designed to identify subsp. novobiosepticus isolates amongst the S. hominis
      isolated from blood samples of patients with malignancy and septicaemia and to
      study their resistance profile. The identification was performed by using three
      simple tests which differentiated between the two sub-species. It was found that
      22.8 per cent of S. hominis isolates belonged to subsp. novobiosepticus.

PMID- 29355152
TI  - Out-of-pocket expenditure due to hepatitis A disease: A study from Kollam
      district, Kerala, India.

PMID- 29355153
TI  - Ocular lesions from copper deficiency.

PMID- 29355154
TI  - Authors' Response.

PMID- 29355155
TI  - Blast effect of shotgun injury in kidney mimicking avulsion of the low pole.

PMID- 29355156
TI  - Relationship between foetal haemoglobin and haematological indices in children
      with sickle cell anaemia from South Western Nigeria.
AB  - BACKGROUND: Foetal haemoglobin (HbF, alpha2gamma2) retards polymerisation of
      haemoglobin (Hb) in sickle cell anaemia (SCA). In Nigeria, studies on the levels
      of HbF and its relationship with haematological indices are scanty. This study
      evaluated HbF concentrations of children with SCA from Southwestern Nigeria and
      correlated the levels with various haematological indices. MATERIALS AND METHODS:
      HbF levels were quantified by high-performance liquid chromatography and
      haematological parameters determined with automated haemoanalyser. The
      relationship between steady-state HbF levels and blood parameters were assessed
      by statistical analyses. RESULTS: The mean HbF of the 91 children with SCA (9.6%
      +/- 5.9%) was significantly higher than 0.5 +/- 0.7% for the 91 age- and sex
      matched controls, P < 0.001. About two-third of children with SCA, sixty (65.9%)
      had low HbF levels (HbF of < 10%) whereas about one-third, 31 (34.1%) had high
      HbF level (HbF of >= 10%). The mean Hb concentration, haematocrit (Hct) and total
      red blood cell count were significantly lower amongst children with SCA, whereas
      the total white blood cell (WBC) counts, neutrophils, monocyte and lymphocyte
      percent, platelet counts, mean corpuscular Hb (MCH) and MCH concentration were
      significantly higher. HbF had a positive but weak correlation with Hct (r = 0.24,
      P = 0.014), Hb concentration (r = 0.21, P = 0.047) and red cell distribution
      width (r = 0.25, P = 0.015) and an inverse correlation with WBC count (r = -0.23,
      P = 0.038). CONCLUSION: Children with SCA had higher levels of HbF than matched
      controls. HbF had an inverse correlation with the WBC count and direct
      relationship with Hct and Hb concentration. It is recommended that routine
      determination of HbF and its induction are essential to maintain optimal
      haematological state of patients with SCD.

PMID- 29355157
TI  - Urinary schistosomiasis in school children of a southern nigerian community 8
      years after the provision of potable water.
AB  - BACKGROUND: Urinary schistosomiasis, one of the neglected tropical diseases, is a
      major infection of public health importance in Nigeria. Control measures include
      the provision of potable water as the main strategy, population-based
      chemotherapy and health education. AIMS AND OBJECTIVES: The aim of this study was
      to determine the effect of the provision of potable water on the prevalence and
      intensity of infection with Schistosoma haematobium in Adim community, Cross
      River State, Nigeria. SUBJECTS AND METHODS: A cross-sectional survey was carried
      out among school and children aged 5-14 years in Adim community in Cross River
      State using the polyamide millipore filter technique and ova detection and count
      compared with the situation that obtained 8 years earlier before the provision of
      potable water. The prevalence and intensity of haematuria and proteinuria by
      reagent strips were also compared between the two eras. RESULTS: The prevalence
      of schistosomiasis was 14.5% compared to 51% in the prepotable water era (P =
      0.001). The intensity of the infection was also significantly reduced between the
      two eras with 1.3% of the children having a severe intensity compared to 4.5% in
      the prepotable water era. CONCLUSIONS/RECOMMENDATIONS: The prevalence and
      intensity of S. haematobium have significantly reduced in this community though
      not yet eliminated. More boreholes need to be provided to make the water more
      accessible. This could be combined with other measures to eradicate S.
      haematobium from this community.

PMID- 29355158
TI  - Histological types of soft-tissue sarcomas at the lagos university teaching
      hospital.
AB  - OBJECTIVE: There is scanty data on histologically diagnosed soft-tissue sarcomas
      in the Nigerian literature. This is due to paucity of facilities for ancillary
      testing as well as a dearth of specialist soft tissue pathologists. Knowledge
      however of the common soft-tissue sarcomas is vital for the establishment of an
      effective sarcoma service. The aim of this study, therefore, was to determine the
      histological spectrum of soft-tissue sarcomas in Lagos, Nigeria. MATERIALS AND
      METHODS: Archival haematoxylin and eosin (H and E)-stained slides were retrieved
      and reviewed by a team of soft-tissue pathologists at the Royal National
      Orthopaedic Hospital, London, UK. Immunohistochemistry and fluorescent in situ
      hybridisation studies were performed on cases without definitive diagnosis on
      routine H and E. RESULTS: Fifty-two cases were studied. The male-to-female ratio
      was 1:1.3, with a median age of 33 years. Most sarcomas (57.5%) were of
      intermediate malignant potential according to 2013 World Health Organization
      classification. Kaposi sarcoma (37.5%), undifferentiated sarcomas (22.5%),
      dermatofibrosarcoma protuberans (15%) and myxofibrosarcomas (7.5%) were the most
      common sarcomas seen in adults. There was no case of liposarcoma. Sarcomas in the
      younger age group (<20 years) accounted for 23.1% of cases with embryonal
      rhabdomyosarcoma accounting for the majority. CONCLUSION: Soft-tissue sarcomas in
      adults in Lagos Nigeria show a different morphologic spectrum than those reported
      in Western countries.

PMID- 29355159
TI  - Colour doppler sonography of the penis in the evaluation of erectile dysfunction:
      Our experience in Abuja, Nigeria.
AB  - BACKGROUND: Erectile dysfunction (ED) is an inability to achieve and maintain
      erectile rigidity sufficient for satisfactory sexual performance. It is either
      organic or psychogenic in origin. This study was aimed at establishing
      vasculogenic causes among patients being evaluated for ED using triplex Doppler
      Ultrasound. PATIENTS AND METHODS: This study was conducted at the Department of
      Radiology, Federal Medical Centre, Abuja, Nigeria from July 2015 to January 2017.
      Thirty-five consecutive patients with the clinical diagnosis of ED were evaluated
      with colour Doppler ultrasound scan using a high-frequency linear transducer. The
      penile scan was done before and after intracavernosal injection of 10-20 MUg
      prostaglandin E1. The waveforms of cavernosal arteries (CAs) were obtained
      alternately using angle of inclination <=60 degrees . The spectral waveforms and
      peak systolic velocities (PSV) of the CA were documented at 5-min intervals, from
      5 to 50 min. RESULTS: PSV of CA varied between 19.5 and 104.4 cm/s (mean: 42.4 +/
      17.6) among the entire patients and between 19.5 and 24.7 cm/s (mean: 21.9 +/-
      1.7) among patients with arteriogenic ED. Arteriogenic ED was found in six
      patients (17%), while venogenic ED was observed in ten patients, which
      constituted 29% of the entire participants. None had combined arteriogenic and
      venogenic ED. Peyronie's disease was observed in seven patients, and none of
      these had vasculogenic ED. CONCLUSION: About 46% of the patients had vasculogenic
      ED. It is therefore imperative that patients with ED benefit from this safe,
      cheap and non-ionising diagnostic modality before initiating therapy as ED
      treatment is cause specific.

PMID- 29355160
TI  - Predictive factors of management outcome in adult patients with mechanical
      intestinal obstruction.
AB  - BACKGROUND: Mechanical intestinal obstruction (MIO) is a common and potentially
      fatal surgical emergency, which constitutes about 20% of all admissions to the
      surgical emergency departments. OBJECTIVE: To determine the predictive factors of
      morbidity and mortality in patients undergoing treatment for MIO at our tertiary
      hospital. PATIENTS AND METHODS: This was a prospective study of consecutive
      patients, 18 years and above, that presented with features of MIO during a 1-year
      period (May 2014 to April 2015). Each patient had resuscitation, comprehensive
      clinical evaluation, appropriate investigations and definitive treatment. The
      data were analysed using SPSS version 22. RESULTS: One hundred and five patients
      were studied. The age range was 18-86 years with a mean (standard deviation) of
      45.6 (14.8) years. There were 54 males with a male to female ratio of 1.1-1. The
      common causes of MIO were post-operative adhesion (48.6%), tumour (25.7%),
      external hernia (15.2%) and volvulus (5.7%). Eighty-four patients (80%) had
      operative intervention while 21 patients (20%) had conservative management.
      Univariate analysis showed that dehydration, tachycardia (>90 bpm), pyrexia,
      abnormal levels of potassium, urea and creatinine, leucocytosis, American Society
      of Anesthesiologists (ASA) status >IIIE, bowel resection, intraoperative blood
      loss >500 ml and duration of surgery >2 h were significant predictors of
      mortality (P < 0.05). Multivariate analysis showed that elevated serum urea at
      hospital presentation and ASA status greater than IIIE were the independent
      predictors of mortality, but none of the factors could independently predict
      morbidity. The most common post-operative complication and cause of death were
      wound infection (29.6%) and sepsis (66.7%). The mortality rate was 14.3%.
      CONCLUSION: The most common cause of MIO was post-operative adhesion. Elevated
      serum urea and ASA status greater than IIIE were the independent predictors of
      mortality.

PMID- 29355161
TI  - Pre- and Post-ductal oxygen saturation among apparently healthy low birth weight
      neonates.
AB  - INTRODUCTION: Reference values of oxygen saturation (SpO2) to guide care of low
      birth weight neonates have been obtained mainly from Caucasians. Data from
      African newborns are lacking. To determine the pre- and post-ductal SpO2values of
      low birth weight neonates within the first 72 h of life, compare SpO2values of
      moderate-late preterm and term low birth weight neonates and determine how mode
      of delivery affected SpO2in the first 24 h of life. METHODOLOGY: An observational
      descriptive study was carried out on apparently healthy low birth weight newborns
      weighing 1500 to <=2499 g. Pre and post ductal SpO2values were recorded at the
      following hours of life: 10-24 h, >24-48 h and >48-72 h using a NONIN(r) pulse
      oximeter. RESULTS: The ranges of pre- and post-ductal SpO2in the study were
      similar for both preterm and term neonates in the study (89%-100%). The mean
      (standard deviation [SD]) pre-ductal SpO2was 95.9% (2.3) and the mean (SD) post
      ductal SpO2was 95.9% (2.1). There was a significant increase in pre-ductal
      SpO2from 10 to 24 h through >48-72 h of life (P = 0.027). The mode of delivery
      did not affect SpO2values within 10-24 h of life. CONCLUSION: The present study
      documented daily single pre- and post-ductal SpO2 values for preterm and term low
      birth weight neonates weighing 1500 g to <2500 g during the first 72 h of life.
      The overall range and mean pre- and post-ductal SpO2 were similar for both
      categories of stable low birth weight neonates in the study. There was no
      significant difference between SpO2ranges for late preterm compared to term low
      birth weight neonates. The results obtained could serve as guide in assessing
      SpO2of low birth weight neonates weighing between 1500 and 2499 g in the first 72
      h of life.

PMID- 29355162
TI  - Effects of low-dose intravenous dexamethasone combined with caudal analgesia on
      post-herniotomy pain.
AB  - BACKGROUND: Caudal analgesia for postoperative pain relief in paediatric day-case
      surgery has been found to be of short duration, hence the need for addition of
      adjuncts to prolong the analgesia. OBJECTIVE: The objective of the study was to
      compare the analgesic effects of caudal block with or without low-dose
      intravenous dexamethasone in children undergoing day-case herniotomy. PATIENTS
      AND METHODS: This was a prospective randomised controlled study conducted in male
      patients, aged between 1 and 7 years scheduled for herniotomy. A total of 94
      patients were randomised into two groups. Group A received intravenous 0.25 mg/kg
      dexamethasone in 5 ml solution, whereas Group B received equivalent volume of
      intravenous normal saline. All the patients had a caudal block. Post-operative
      pain was assessed and recorded in post-anaesthesia care unit (PACU) using
      objective pain scale. Time to first analgesia request (TFA), pain scores and
      complications were documented. Data were analysed using Statistical Package for
      the Social Sciences version 21.0. RESULTS: A total of 94 patients were analysed
      with a mean age of 3.30 +/- 1.67 and 3.06 +/- 1.50 years for Groups A and B,
      respectively. The TFA request was 654.18 +/- 31.56 and 261.50 +/- 10.82 min in
      Groups A and B, respectively, P = 0.0001. Postoperatively, in the PACU, there was
      statistically significant difference in pain score between the two groups at 0,
      30, 60, 120, 180 and 240 min (P = 0.0001) all through. CONCLUSION: The use of low
      dose intravenous dexamethasone (0.25 mg/kg) in combination with caudal block
      prolonged duration of analgesia, reduced pain scores and analgesic consumption
      postoperatively, in children undergoing day-case herniotomy.

PMID- 29355163
TI  - The role of transrectal ultrasound-guided fine-needle aspiration biopsy in the
      diagnosis of prostate cancer: Sextant versus extended protocol.
AB  - AIM AND OBJECTIVES: The aim of this study is to compare the prostate cancer
      detection rates of sextant and extended transrectal ultrasound (TRUS)-guided fine
      needle aspiration biopsy (FNAB) protocols. MATERIALS AND METHODS: This was a
      prospective study of 96 patients investigated for prostate cancer. An extended 10
      aspiration TRUS-guided FNAB using a 22G Echotip Chiba needle was performed.
      Inclusion criteria included the presence of one or more of the following:
      Abnormal digital rectal examination (DRE) findings, persistently elevated
      prostate specific antigen, and abnormal prostatic imaging. A set of traditional
      sextant aspirations were carried out as well as four laterally guided aspirations
      taken from the middle base of the peripheral zone on either side. The cancer
      detection rates of sextant and extended (combination of sextant and lateral) FNAB
      protocols were determined and compared. The value of P < 0.05 was considered
      statistically significant. RESULTS: The overall cancer detection rate was 24%.
      Benign cases were reported in 71.8% of patients and 4.2% reported as suspicious.
      Of the 23 patients' aspirations positive for malignancy, 16 (69.6%) were
      detectable by the sextant protocol while the lateral protocol detected 21
      (91.3%). Two cancers were detected by the sextant protocol only (where the
      lateral technique was negative for malignancy), 7 cancers were detected by the
      lateral protocol only while 14 cancers were positive in both the sextant and
      lateral protocols. The extended protocol showed a statistically significant 30.4%
      increase in cancer detection over the traditional sextant (P = 0.007).
      CONCLUSION: The extended protocol rather than the sextant protocol should be
      offered to patients who require FNAB of the prostate as the optimum FNAB
      protocol.

PMID- 29355164
TI  - Serum level of prostate-specific antigen in diabetic patients in Basrah, Iraq.
AB  - OBJECTIVES: The aim of this study was to determine the effect of type 2 diabetes
      mellitus (DM) on the serum level of prostate-specific antigen (PSA) in men in
      Basrah, Iraq. PATIENTS AND METHODS: A case-control study was done including 70
      confirmed type 2 diabetic patients and 70 non-diabetic persons. Data about age
      and family history of diabetes were collected. For diabetic patients, data
      related to disease history were also enquired about. Weight and height were
      measured and body mass index (BMI) was calculated. Blood examination was done to
      estimate fasting plasma glucose and PSA. RESULTS: The mean ages of diabetic and
      non-diabetic patients were 55.2 +/- 10.5 and 55.9 +/- 10.9 years, respectively.
      The mean total serum PSA was significantly lower among diabetic than non-diabetic
      men (1.97 +/- 1.05 ng/ml vs. 2.60 +/- 1.22 ng/ml, respectively, P = 0.001). The
      multivariate linear regression analysis showed that age, DM and BMI were
      independent predictors of serum PSA variation. Age was significantly related to
      PSA in non-diabetics, but not in diabetic patients. CONCLUSION: Serum PSA level
      is significantly lower and less age dependent in type 2 diabetic patients than in
      non-diabetics. Therefore, DM should be considered in setting of PSA threshold
      when screening for prostate cancer.

PMID- 29355165
TI  - Comparison of efficacy of cell block versus conventional smear study in exudative
      fluids.
AB  - INTRODUCTION: Cytological examination of serous effusions helps in staging,
      prognostication and management of patients with malignancy. The method has
      disadvantage of lower sensitivity in differentiating reactive atypical
      mesothelial cells from malignant cells. AIM: The aim of this study is to compare
      the cytological features of pleural and peritoneal exudative fluids by
      conventional smear (CS) method and cell block (CB) method and also to assess the
      utility of a combined approach for cytodiagnosis of these effusions. MATERIALS
      AND METHODS: One hundred and fifty-three pleural and peritoneal exudative fluid
      samples were subjected to evaluation by both CS and CB methods over a period of 2
      years. Cellularity, architecture patterns, morphological features and yield for
      malignancy were compared, using the two methods. Sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV) and accuracy for
      diagnosing malignancy were calculated by both methods, using histology as a gold
      standard. RESULTS: CB method provided higher cellularity, better architectural
      patterns and additional yield for malignancy as compared to CS method (P <
      0.005). Sensitivity, specificity, PPV, NPV, and accuracy by CS method were 69.2%,
      95%, 56.25%, 97.08% and 92.8%, while by CB method were 92.30%, 99.2%, 92.30%,
      99.28% and 98.6%. CONCLUSION: The present study shows that it is advisable to
      routinely make CBs before discarding specimens that are suspicious for malignancy
      by smear examination.

PMID- 29355166
TI  - Giant cell tumour of the clavicle: A rare presentation of a locally aggressive
      tumour.
AB  - We report a case of a 28-year-old female who presents with painless,
      progressively increasing left upper chest swelling of 6 months duration.
      Examination revealed a 20 by 10 cm firm mass arising from the clavicle. She was
      investigated and a diagnosis established based on the histological report. The
      tumour was excised with a wide margin and reconstruction done with an autogenous
      fibula graft. Full functional ability was restored in limb with the radiological
      union. After 5 years of regular follow-up, there was no evidence of recurrence
      and shoulder function remained excellent. The successful management of this
      patient shows wide local excision and reconstruction as an excellent surgical
      option in treating giant cell tumour of the clavicle.

PMID- 29355167
TI  - Preoperative bowel preparation complicated by lethal hypermagnesaemia and acute
      nephropathy.
AB  - Hypermagnesaemia is an uncommon but serious disorder. An elderly woman presented
      with severe cardiovascular collapse, neurologic depression and acute nephropathy,
      following bowel preparation. Urgent laboratory tests revealed serum magnesium
      level of 7.5 mmol/L (normal = 0.75-1.05 mmol/L). Prompt resuscitation and
      treatment of the hypermagnesaemia included intravenous calcium chloride as a
      physiological antagonist, fluid infusion and frusemide to aid renal excretion of
      magnesium. There are few case reports of patients who survived hypermagnesaemia
      levels >7 mmol/L. This is a case report of near-fatal hypermagnesaemia which
      resolved following early diagnosis and treatment. Hypermagnesaemia may be
      difficult to diagnose because serum magnesium is not checked routinely and many
      clinicians are unfamiliar with this uncommon condition. It is a diagnosis of
      exclusion and may not be recognised as a cause of neurologic or cardiorespiratory
      depression. Hypermagnesaemia should be considered as a possible diagnosis in
      elderly or high-risk patients presenting with such symptomatology.

PMID- 29355170
TI  - Renal physiology: TRPC5 inhibition to treat progressive kidney disease.

PMID- 29355171
TI  - Kidney cancer: PBRM1 loss promotes tumour response to immunotherapy.

PMID- 29355168
TI  - Reproductive health and pregnancy in women with chronic kidney disease.
AB  - Chronic kidney disease (CKD) is associated with reduced fertility and an
      increased risk of adverse pregnancy outcomes. Rates of pre-eclampsia, fetal
      growth restriction and preterm delivery increase incrementally with the severity
      of CKD and proteinuria. Pre-pregnancy counselling can facilitate informed
      decision-making. Safe and effective contraception is required for women who wish
      to delay or avoid pregnancy. Pregnancy planning for women who wish to conceive
      involves appropriate substitution of known teratogens - including mycophenolate
      mofetil, angiotensin blockers and cyclophosphamide - and can aid optimization of
      disease control. However, pregnancy, which can occur in women with any stage of
      CKD, can exacerbate comorbidities such as anaemia, vitamin D deficiency and
      hypertension. Increased haemodialysis provision is associated with improved
      pregnancy outcomes for women on dialysis. Diagnosis of pre-eclampsia in women
      with CKD is complicated in patients with pre-existing hypertension and
      proteinuria but can be improved by the use of vasoactive biomarkers as well as
      placental and fetal Doppler ultrasound. Pregnancy data for newer drugs used in
      CKD are limited as pregnancy and CKD are common exclusion criteria for drug and
      intervention trials. Although prospective data may be available for older drugs,
      the use of most drugs in pregnancy is based on retrospective data and expert
      consensus.

PMID- 29355172
TI  - Acute kidney injury: Macrophage extracellular traps in rhabdomyolysis-induced
      AKI.

PMID- 29355169
TI  - Sex and gender disparities in the epidemiology and outcomes of chronic kidney
      disease.
AB  - Improved understanding of sex and gender-specific differences in the aetiology,
      mechanisms and epidemiology of chronic kidney disease (CKD) could help
      nephrologists better address the needs of their patients. Population-based
      studies indicate that CKD epidemiology differs by sex, affecting more women than
      men, especially with regard to stage G3 CKD. The effects of longer life
      expectancy on the natural decline of glomerular filtration rate (GFR) with age,
      as well as potential overdiagnosis of CKD through the inappropriate use of GFR
      equations, might be in part responsible for the greater prevalence of CKD in
      women. Somewhat paradoxically, there seems to be a preponderance of men among
      patients starting renal replacement therapy (RRT); the protective effects of
      oestrogens in women and/or the damaging effects of testosterone, together with
      unhealthier lifestyles, might cause kidney function to decline faster in men than
      in women. Additionally, elderly women seem to be more inclined to choose
      conservative care instead of RRT. Dissimilarities between the sexes are also
      apparent in the outcomes of CKD. In patients with predialysis CKD, mortality is
      higher in men than women; however, this difference disappears for patients on
      RRT. Although access to living donor kidneys among men and women seems equal,
      women have reduced access to deceased donor transplantation. Lastly, health
      related quality of life while on RRT is poorer in women than men, and women
      report a higher burden of symptoms. These findings provide insights into
      differences in the underlying pathophysiology of disease as well as societal
      factors that can be addressed to reduce disparities in access to care and
      outcomes for patients with CKD.

PMID- 29355174
TI  - Acute kidney injury: Antioxidants do not PRESERVE kidney function after contrast
      exposure.

PMID- 29355173
TI  - Paradigms of acute kidney injury in the intensive care setting.
AB  - Acute kidney injury (AKI) is a heterogeneous clinical syndrome that has multiple
      aetiologies, variable pathogenesis and diverse outcomes. However, these
      heterogeneities are not reflected in current approaches to the diagnosis and, to
      some degree, treatment of AKI. For example, congestive heart failure and
      dehydration can produce identical changes in serum creatinine level and urine
      output (parameters that are used to define AKI); however, they differ vastly in
      their physiological contexts and demand completely opposite treatments. AKI is
      often still considered to be a homogeneous clinical entity, which implies a
      uniform pathogenesis and a well-defined prognosis. As a consequence, efforts to
      find effective AKI treatments have been hampered by a lack of clear clinical
      classifications for various types of AKI. In addition, subclassification of AKI
      into subclinical phenotypes - for example, on the basis of protein biomarkers and
      other in vitro diagnostics that take into account disease aetiology and
      underlying pathogenesis - might be necessary to develop therapeutic approaches
      that effectively target the widely differing pathomechanisms of AKI. In this
      Review, we discuss the major subtypes of AKI that are associated with sepsis,
      major surgery, renal hypoperfusion and nephrotoxin exposure -situations that are
      typically seen in the intensive care setting. We consider differences and
      similarities in their phenotype, pathogenesis and outcomes and how this
      information might be used to guide treatment.

PMID- 29355175
TI  - Chronic kidney disease: Key role of exosomes in albumin-induced inflammation.

PMID- 29355176
TI  - Leadership in dentistry: findings from new tool to measure clinical leadership.
AB  - Background: In England, the recent reorganization of the National Health Service
      has led to the development of local dental networks and an emerging narrative on
      the importance of clinical leadership in dentistry. Analogous to clinical
      commissioning groups, local dental networks ensure general dental practitioners
      (GDPs) influence the delivery of local services. However, little is known about
      what GDPs think clinical leadership is and whether the construct has meaning. The
      aim of this study was to explore the structure of a pilot questionnaire to
      determine the qualities that GDPs deem are important and to use a data reduction
      methodology to produce a tool to measure clinical leadership. Methods: A 61-item
      questionnaire was distributed to GDPs across the North West of England. GDPs were
      asked to rate the level of importance of each item using a 7-point Likert scale.
      Principal component analysis and direct oblimin rotation was used to examine for
      factor loadings within the questionnaire. Internal validity was tested by
      Cronbach's alpha. Results: Two principle factors emerged: "how to lead" and "how
      not to lead". Individually, the item "I think it is important to have integrity"
      was rated as the most important. Conclusion: The study developed a refined
      questionnaire that captures the important qualities of clinical leadership in
      dentistry. This is the first questionnaire that has been developed to capture
      important leadership attributes for GDPs.

PMID- 29355177
TI  - Facilitating the implementation of evidence- based practice through contextual
      support and nursing leadership.
AB  - Background/purpose: Nurse managers (NMs) play an important role promoting
      evidence-based practice (EBP) on clinical units within hospitals. However, there
      is a dearth of research focused on NM perspectives about institutional contextual
      factors to support the goal of EBP on the clinical unit. The purpose of this
      article is to identify contextual factors described by NMs to drive change and
      facilitate EBP at the unit level, comparing and contrasting these perspectives
      across nursing units. Methods: This study employed a qualitative descriptive
      design using interviews with nine NMs who were participating in a large
      effectiveness study. To stratify the sample, NMs were selected from nursing units
      designated as high or low performing based on implementation of EBP
      interventions, scores on the Meyer and Goes research use scale, and fall rates.
      Descriptive content analysis was used to identify themes that reflect the complex
      nature of infrastructure described by NMs and contextual influences that
      supported or hindered their promotion of EBP on the clinical unit. Results: NMs
      perceived workplace culture, structure, and resources as facilitators or barriers
      to empowering nurses under their supervision to use EBP and drive change. A
      workplace culture that provides clear communication of EBP goals or regulatory
      changes, direct contact with CEOs, and clear expectations supported NMs in their
      promotion of EBP on their units. High-performing unit NMs described a structure
      that included nursing-specific committees, allowing nurses to drive change and
      EBP from within the unit. NMs from high-performing units were more likely to
      articulate internal resources, such as quality-monitoring departments, as
      critical to the implementation of EBP on their units. This study contributes to a
      deeper understanding of institutional contextual factors that can be used to
      support NMs in their efforts to drive EBP changes at the unit level.

PMID- 29355178
TI  - A review of family carers' experiences of hospital discharge for people with
      dementia, and the rationale for involving service users in health research.
AB  - : In the UK, service user involvement is an important factor in health policy,
      and obtaining research funding. It may be helpful in expanding our knowledge in
      areas where research evidence is poor such as experiences of hospital discharge
      planning for the family carers of people with dementia. Methods: A rapid review.
      All study designs published in the English language were eligible for inclusion.
      Databases included: Medline, Embase, CINAHL, PsycInfo, Cochrane library and Web
      of Knowledge. A qualitative analysis was undertaken. Results: Four themes were
      identified: preparation for hospital discharge - dissatisfaction with being kept
      informed, discharge arrangements and management of conditions; little time to
      prepare. Communication between staff and families at discharge - insufficient
      communication regarding services, not being listened to and being undervalued as
      a resource could compromise post-discharge care. Support services post discharge 
      carers need help negotiating, and working with, services with regard to timing,
      and meeting requirements. Coping post hospital discharge - inadequate
      understanding about ability to cope, and patient's impairment, and family
      conflict over care may lead to unnecessary re-admission to hospital, or long term
      care. Evidence of specialist dementia models at discharge is described.
      Discussion: Carers are not always involved in hospital discharge planning as well
      as they might be. Issues are complex and depend on a number of factors. Poor
      communication can be overcome and carers can be better supported to cope post
      discharge as illustrated in the dementia models. The evidence base is weak but
      the absence of evidence does not indicate an absence of good practice.
      Conclusion: Carers who may feel their world is far removed from the academic
      world may not ordinarily participate in research studies. Service users, as co
      researchers, may be able to improve trust and rapport between research and
      communities, collect fresh insights and gain deeper and more insightful data from
      participants.

PMID- 29355179
TI  - Clinical leadership development and education for nurses: prospects and
      opportunities.
AB  - With the implementation of the Affordable Care Act, elevated roles for nurses of
      care coordinator, clinical nurse leader, and advanced practice registered nurse
      have come to the forefront. Because change occurs so fast, matching development
      and education to job requirements is a challenging forecasting endeavor. The
      purpose of this article is to envision clinical leadership development and
      education opportunities for three emerging roles. The adoption of a common
      framework for intentional leadership development is proposed for clinical
      leadership development across the continuum of care. Solutions of innovation and
      interdependency are framed as core concepts that serve as an opportunity to
      better inform clinical leadership development and education. Additionally,
      strategies are proposed to advance knowledge, skills, and abilities for crucial
      implementation of improvements and new solutions at the point of care.

PMID- 29355180
TI  - The Nursing Leadership Institute program evaluation: a critique.
AB  - A theory-driven program evaluation was conducted for a nursing leadership
      program, as a collaborative project between university faculty, the nurses'
      union, the provincial Ministry of Health, and its chief nursing officers. A
      collaborative logic model process was used to engage stakeholders, and mixed
      methods approaches were used to answer evaluation questions. Despite
      demonstrated, successful outcomes, the leadership program was not supported with
      continued funding. This paper examines what happened during the evaluation
      process: What factors failed to sustain this program?

PMID- 29355181
TI  - Deliberative democracy in health care: current challenges and future prospects.
AB  - Background: There is a vast body of literature on deliberative, participative, or
      engaged democracy. In the area of health care there is a rapidly expanding
      literature on deliberative democracy as embodied in various notions of public
      engagement, shared decision-making (SDM), patient-centered care, and patient/care
      provider autonomy over the past few decades. It is useful to review such
      literature to get a sense of the challenges and prospects of introducing
      deliberative democracy in health care. Objective: This paper reviews the key
      literature on deliberative democracy and SDM in health care settings with a focus
      on identifying the main challenges of promoting this approach in health care, and
      recognizing its progress so far for mapping out its future prospects in the
      context of advanced countries. Method: Several databases were searched to
      identify the literature pertinent to the subject of this study. A total of 56 key
      studies in English were identified and reviewed carefully for indications and
      evidence of challenges and/or promising avenues of promoting deliberative
      democracy in health care. Results: Time pressure, lack of financial motivation,
      entrenched professional interests, informational imbalance, practical
      feasibility, cost, diversity of decisions, and contextual factors are noted as
      the main challenges. As for the prospects, greater clarity on conception of
      public engagement and policy objectives, real commitment of the authorities to
      public input, documenting evidence of the effectiveness of public involvement,
      development of patient decision supports, training of health professionals in
      SDM, and use of multiple and flexible methods of engagement leadership suited to
      specific contexts are the main findings in the reviewed literature. Conclusion:
      Seeking deliberative democracy in health care is both challenging and rewarding.
      The challenges have been more or less identified. However, its prospects are
      potentially significant. Such prospects are more likely to materialize if
      deliberative democracy is pursued more systematically in the broader
      sociopolitical domains.

PMID- 29355182
TI  - Assessment of the management factors that influence the development of preventive
      care in the New South Wales public dental service.
AB  - Background: Oral diseases, particularly dental caries, remain one of the most
      common chronic health problems for adolescents, and are a major public health
      concern. Public dental services in New South Wales, Australia offer free clinical
      care and preventive advice to all adolescents under 18 years of age, particularly
      those from disadvantaged backgrounds. This care is provided by dental therapists
      and oral health therapists (therapists). It is incumbent upon clinical directors
      (CDs) and health service managers (HSMs) to ensure that the appropriate clinical
      preventive care is offered by clinicians to all their patients. The aims of this
      study were to 1) explore CDs' and HSMs' perceptions of the factors that could
      support the delivery of preventive care to adolescents, and to 2) record the
      strategies they have utilized to help therapists provide preventive care to
      adolescents. Subjects and methods: In-depth, semistructured interviews were
      undertaken with 19 CDs and HSMs from across NSW local health districts. A
      framework matrix was used to systematically code data and enable key themes to be
      identified for analysis. Results: The 19 CDs and HSMs reported that fiscal
      accountability and meeting performance targets impacted on the levels and types
      of preventive care provided by therapists. Participants suggested that
      professional clinical structures for continuous quality improvement should be
      implemented and monitored, and that an adequate workforce mix and more resources
      for preventive dental care activities would enhance therapists' ability to
      provide appropriate levels of preventive care. CDs and HSMs stated that
      capitalizing on the strengths of visiting pediatric dental specialists and
      working with local health district clinical leaders would be a practical way to
      improve models of preventive oral health care for adolescents. Conclusion: The
      main issue raised in this study is that preventive dentistry per se lacks strong
      support from the central funding agency, and that increasing prevention
      activities is not a simple task of changing regulations or increasing
      professional education.

PMID- 29355183
TI  - Use of CAHPS(r) patient experience survey data as part of a patient-centered
      medical home quality improvement initiative.
AB  - Objective: To describe how practice leaders used Consumer Assessment of
      Healthcare Providers and Systems (CAHPS(r)) Clinician and Group (CG-CAHPS) data
      in transitioning toward a patient-centered medical home (PCMH). Study design:
      Interviews conducted at 14 primary care practices within a large urban Federally
      Qualified Health Center in California. Participants: Thirty-eight interviews were
      conducted with lead physicians (n=13), site clinic administrators (n=13), nurse
      supervisors (n=10), and executive leadership (n=2). Results: Seven themes were
      identified on how practice leaders used CG-CAHPS data for PCMH transformation.
      CAHPS(r) was used: 1) for quality improvement (QI) and focusing changes for PCMH
      transformation; 2) to maintain focus on patient experience; 3) alongside other
      data; 4) for monitoring site-level trends and changes; 5) to identify, analyze,
      and monitor areas for improvement; 6) for provider-level performance monitoring
      and individual coaching within a transparent environment of accountability; and
      7) for PCMH transformation, but changes to instrument length, reading level, and
      the wording of specific items were suggested. Conclusion: Practice leaders used
      CG-CAHPS data to implement QI, develop a shared vision, and coach providers and
      staff on performance. They described how CAHPS(r) helped to improve the patient
      experience in the PCMH model, including access to routine and urgent care, wait
      times, provider spending enough time and listening carefully, and courteousness
      of staff. Regular reporting, reviewing, and discussing of patient-experience data
      alongside other clinical quality and productivity measures at multilevels of the
      organization was critical in maximizing the use of CAHPS(r) data as PCMH changes
      were made. In sum, this study found that a system-wide accountability and data
      monitoring structure relying on a standardized and actionable patient-experience
      survey, such as CG-CAHPS, is key to supporting the continuous QI needed for
      moving beyond formal PCMH recognition to maximizing primary care medical home
      transformation.

PMID- 29355184
TI  - Clinical leadership development in postgraduate medical education and training:
      policy, strategy, and delivery in the UK National Health Service.
AB  - Achieving high quality health care against a background of continual change,
      increasing demand, and shrinking financial resource is a major challenge.
      However, there is significant international evidence that when clinicians use
      their voices and values to engage with system delivery, operational efficiency
      and care outcomes are improved. In the UK National Health Service, the
      traditional divide between doctors and managers is being bridged, as clinical
      leadership is now foregrounded as an important organizational priority. There are
      60,000 doctors in postgraduate training (junior doctors) in the UK who provide
      the majority of front-line patient care and form an "operating core" of most
      health care organizations. This group of doctors is therefore seen as an
      important resource in initiating, championing, and delivering improvement in the
      quality of patient care. This paper provides a brief overview of leadership
      theories and constructs that have been used to develop a raft of interventions to
      develop leadership capability among junior doctors. We explore some of the
      approaches used, including competency frameworks, talent management, shared
      learning, clinical fellowships, and quality improvement. A new paradigm is
      identified as necessary to make a difference at a local level, which moves
      learning and leadership away from developing "leaders", to a more inclusive model
      of developing relationships between individuals within organizations. This shifts
      the emphasis from the development of a "heroic" individual leader to a more
      distributed model, where organizations are "leader-ful" and not just "well led"
      and leadership is centered on a shared vision owned by whole teams working on the
      frontline.

PMID- 29355186
TI  - Design, implementation, and demographic differences of HEAL: a self-report health
      care leadership instrument.
AB  - The medical community has recognized the importance of leadership skills among
      its members. While numerous leadership assessment tools exist at present, few are
      specifically tailored to the unique health care environment. The study team
      designed a 24-item survey (Healthcare Evaluation & Assessment of Leadership
      [HEAL]) to measure leadership competency based on the core competencies and core
      principles of the Duke Healthcare Leadership Model. A novel digital platform was
      created for use on handheld devices to facilitate its distribution and
      completion. This pilot phase involved 126 health care professionals self
      assessing their leadership abilities. The study aimed to determine both the
      content validity of the survey and the feasibility of its implementation and use.
      The digital platform for survey implementation was easy to complete, and there
      were no technical problems with survey use or data collection. With regard to
      reliability, initial survey results revealed that each core leadership tenet met
      or exceeded the reliability cutoff of 0.7. In self-assessment of leadership,
      women scored themselves higher than men in questions related to patient
      centeredness (P=0.016). When stratified by age, younger providers rated
      themselves lower with regard to emotional intelligence and integrity. There were
      no differences in self-assessment when stratified by medical specialty. While
      only a pilot study, initial data suggest that HEAL is a reliable and easy-to
      administer survey for health care leadership assessment. Differences in responses
      by sex and age with respect to patient centeredness, integrity, and emotional
      intelligence raise questions about how providers view themselves amid complex
      medical teams. As the survey is refined and further administered, HEAL will be
      used not only as a self-assessment tool but also in "360" evaluation formats.

PMID- 29355187
TI  - Health care leadership development and training: progress and pitfalls.
AB  - Formal training in the multifaceted components of leadership is now accepted as
      highly desirable for health care leaders. Despite natural leadership instincts,
      some core leadership competencies ("differentiating competencies") must be
      formally taught or refined. Leadership development may begin at an early career
      stage. Despite the recognized need, the number of comprehensive leadership
      development opportunities is still limited. Leadership training programs in
      health care were started primarily as internal institutional curricula, with a
      limited scope, for the development of faculty or practitioners. More
      comprehensive national leadership programs were developed in response to the
      needs of specific cohorts of individuals, such as programs for women, which are
      designed to increase the ranks of senior women leaders in the health sciences. As
      some programs reach their 20th year of existence, outcomes research has shown
      that health care leadership training is most effective when it takes place over
      time, is comprehensive and interdisciplinary, and incorporates
      individual/institutional projects allowing participants immediate practical
      application of their newly acquired skills. The training should envelop all the
      traditional health care domains of clinical practice, education, and research, so
      the leader may understand all the activities taking place under his/her
      leadership. Early career leadership training helps to develop a pipeline of
      leaders for the future, setting the foundation for further development of those
      who may chose to pursue significant leadership opportunities later in their
      career. A combination of early and mid-to-late career development may represent
      the optimal training for effective leaders. More training programs are needed to
      make comprehensive leadership development widely accessible to a greater number
      of potential health care leaders. This paper addresses the skills that health
      care leaders should develop, the optimal leadership development concepts that
      must be acquired to succeed as a health care leader today, some resources for
      where such training may be obtained, and what gaps are still present in today's
      system.

PMID- 29355188
TI  - Decisions and the involvement of cancer patient survivors: a moral imperative.
AB  - Purpose: The aim of this study was to review the experiences of direct
      involvement in patient survivorship for treatment and research. Methods: This is
      a narrative-focused review of the following two recent experiences of patient
      involvement: the Chordoma Foundation and the Triple Negative Breast Cancer
      Foundation. Results: These two examples represent concrete experiences that
      patients have built to favor a real involvement in the care and treatment of
      tumors. These experiences are profoundly modifying how cancer research is
      conducted and draw attention to the psychosocial dimensions of health care.
      Conclusion: These examples represent the new scenario in which modern medicine
      faces completely new challenges, copes with new needs, and cooperates with new
      health care professionals. Implications: Involving patients in a new perspective
      raises practical and ethical challenges for organizations to work together, for
      health providers to be professionally skilled and for the government to promote
      safeguarding policies.

PMID- 29355190
TI  - An efficient method for link prediction in weighted multiplex networks.
AB  - Background: A great variety of artificial and natural systems can be abstracted
      into a set of entities interacting with each other. Such abstractions can very
      well represent the underlying dynamics of the system when modeled as the network
      of vertices coupled by edges. Prediction of dynamics in these structures based on
      topological attribute or dependency relations is an important task. Link
      Prediction in such complex networks is regarded useful in almost all types of
      networks as it can be used to extract missing information, identify spurious
      interactions, and evaluate network evolving mechanisms. Various similarity and
      likelihood-based indices have been employed to infer different topological and
      relation-based information to form a link prediction algorithm. These algorithms,
      however, are too specific to the domain and do not encapsulate the generic nature
      of the real-world information. In most natural and engineered systems, the
      entities are linked with multiple types of associations and relations which play
      a factor in the dynamics of the network. It forms multiple subsystems or multiple
      layers of networked information. These networks are regarded as Multiplex
      Networks. Methods: This work presents an approach for link prediction in
      Multiplex networks where the associations are learned from the multiple layers of
      networks for link prediction purposes. Most of the real-world networks are
      represented as weighted networks. Weight prediction coupled with Link Prediction
      can be of great use. Link scores are received using various similarity measures
      and used to predict weights. This work further proposes and testifies a strategy
      for weight prediction. Results and Conclusions: This work successfully proposes
      an algorithm for Weight Prediction using Link similarity measures on multiplex
      networks. The predicted weights show very less deviation from their actual
      weights. In comparison to other indices, the proposed method has a far low error
      rate and outperforms them concerning the metric performance NRMSE.

PMID- 29355189
TI  - Regulatory mechanisms for absenteeism in the health sector: a systematic review
      of strategies and their implementation.
AB  - Background: A systematic review was undertaken to identify regulatory mechanisms
      aimed at mitigating health care worker absenteeism, to describe where and how
      they have been implemented as well as their possible effects. The goal was to
      propose potential policy options for managing the problem of absenteeism among
      human resources for health in low- and middle-income countries. Mechanisms
      described in this review are at the local workplace and broader national policy
      level. Methods: A comprehensive online search was conducted on EMBASE, CINAHL,
      PubMed, Google Scholar, Google, and Social Science Citation Index using MEDLINE
      search terms. Retrieved studies were uploaded onto reference manager and screened
      by two independent reviewers. Only publications in English were included. Data
      were extracted and synthesized according to the objectives of the review.
      Results: Twenty six of the 4,975 published articles retrieved were included. All
      were from high-income countries and covered all cadres of health workers. The
      regulatory mechanisms and possible effects include 1) organizational-level
      mechanisms being reported as effective in curbing absenteeism in low- and middle
      income countries (LMICs); 2) prohibition of private sector activities in LMICs
      offering benefits but presenting a challenge for the government to monitor the
      health workforce; 3) contractual changes from temporary to fixed posts having
      been associated with no reduction in absenteeism and not being appropriate for
      LMICs; 4) multifaceted work interventions being implemented in most settings; 5)
      the possibility of using financial and incentive regulatory mechanisms in LMICs;
      6) health intervention mechanisms reducing absenteeism when integrated with
      exercise programs; and 7) attendance by legislation during emergencies being
      criticized for violating human rights in the United States and not being
      effective in curbing absenteeism. Conclusion: Most countries have applied
      multiple strategies to mitigate health care worker absenteeism. The success of
      these interventions is heavily influenced by the context within which they are
      applied.

PMID- 29355191
TI  - Financial incentive schemes in primary care.
AB  - Pay-for-performance (P4P) schemes have become increasingly common in primary
      care, and this article reviews their impact. It is based primarily on existing
      systematic reviews. The evidence suggests that P4P schemes can change health
      professionals' behavior and improve recorded disease management of those clinical
      processes that are incentivized. P4P may narrow inequalities in performance
      comparing deprived with nondeprived areas. However, such schemes have unintended
      consequences. Whether P4P improves the patient experience, the outcomes of care
      or population health is less clear. These practical uncertainties mirror the
      ethical concerns of many clinicians that a reductionist approach to managing
      markers of chronic disease runs counter to the humanitarian values of family
      practice. The variation in P4P schemes between countries reflects different
      historical and organizational contexts. With so much uncertainty regarding the
      effects of P4P, policy makers are well advised to proceed carefully with the
      implementation of such schemes until and unless clearer evidence for their cost
      benefit emerges.

PMID- 29355192
TI  - A silent shift? The precarisation of the Dutch rental housing market.
AB  - The traditional Dutch rental contract is permanent (i.e. time unlimited), but
      there are indications that in recent years the number of temporary rental
      contracts has increased considerably. Dutch housing policy appears to be
      responding to this by pursuing deregulation of the conditions under which
      temporary rent is permitted. It is in this regard startling that there is no
      reliable data available about the size or character of the temporary sector, and
      it has thus far not attracted any scholarly attention. Given that temporary rent
      can be viewed as a form of precarisation, a transfer of risk to citizens, with
      corresponding negative effects on the lives of those involved, it is imperative
      to close this knowledge gap. This paper is a first attempt to do this. Firstly, I
      systematically review the scarce evidence that is currently available, and
      secondly, I explore why the rise of temporary rent has thus far failed to
      stimulate any social debate; it appears to constitute a silent precarisation that
      contrasts with the politically sensitive issue of labour precarisation. In doing
      so, I will identify the research questions that must be answered if the
      significance of this process for both tenants and wider welfare-state
      restructuring is to be fully understood.

PMID- 29355193
TI  - Improving surgeon utilization in an orthopedic department using simulation
      modeling.
AB  - Purpose: Worldwide more than two billion people lack appropriate access to
      surgical services due to mismatch between existing human resource and patient
      demands. Improving utilization of existing workforce capacity can reduce the
      existing gap between surgical demand and available workforce capacity. In this
      paper, the authors use discrete event simulation to explore the care process at
      an orthopedic department. Our main focus is improving utilization of surgeons
      while minimizing patient wait time. Methods: The authors collaborated with
      orthopedic department personnel to map the current operations of orthopedic care
      process in order to identify factors that influence poor surgeons utilization and
      high patient waiting time. The authors used an observational approach to collect
      data. The developed model was validated by comparing the simulation output with
      the actual patient data that were collected from the studied orthopedic care
      process. The authors developed a proposal scenario to show how to improve surgeon
      utilization. Results: The simulation results showed that if ancillary services
      could be performed before the start of clinic examination services, the
      orthopedic care process could be highly improved. That is, improved surgeon
      utilization and reduced patient waiting time. Simulation results demonstrate that
      with improved surgeon utilizations, up to 55% increase of future demand can be
      accommodated without patients reaching current waiting time at this clinic, thus,
      improving patient access to health care services. Conclusion: This study shows
      how simulation modeling can be used to improve health care processes. This study
      was limited to a single care process; however the findings can be applied to
      improve other orthopedic care process with similar operational characteristics.

PMID- 29355194
TI  - Closure of a local public hospital in Korea: focusing on the organizational life
      cycle.
AB  - Just as living organisms have a creation-maintenance-extinction life cycle,
      organizations also have a life cycle. Private organizations will not survive if
      they fail to acquire necessary resources through market competition. Public
      organizations, however, continue to survive because the government has provided
      financial support in order to enhance public interest. Only a few public
      organizations in Korea have closed. With the introduction of new public
      management since the economic crisis in 1997, however, public organizations have
      had to compete with private organizations. Public hospitals are not free to open
      or close their business. They are also controlled by the government in terms of
      their prices, management, budgets, and operations. As they pursue public interest
      by fulfilling the government's order such as providing free or lower-priced care
      to the vulnerable population, they tend to provide a lower quality of care and
      suffer a financial burden. Employing a case study analysis, this study attempts
      to understand the external environment that local public hospitals face. The
      fundamental problem of local public hospitals in Korea is the value conflict
      between public interest and profitability. Local public hospitals are required to
      pursue public interest by assignment of a public mission including building a
      medical safety net for low-income patients and managing nonprofitable medical
      facilities and emergent health care situations. At the same time, they are
      required to pursue profitability by achieving high-quality care through
      competition and the operation of an independent, self-supporting system according
      to private business logic. Under such paradoxical situations, a political
      decision may cause an unexpected result.

PMID- 29355195
TI  - The relationship between leadership and physician well-being: a scoping review.
AB  - To date, research has established the individual and organizational factors that
      impair well-being. Thus, we are aware of the organizational "cogs and wheels"
      that drive well-being, and there is a sense that we can potentially utilize
      effective leadership to push and pull these in the appropriate directions.
      However, reviews of leadership in health care point to the lack of academic rigor
      and difficulty in reaching solid conclusions. Conversely, there is an accepted
      belief that the most important determinant of the development and maintenance of
      cultures is current - and future - leadership. Thus, leadership is assumed to be
      an important element of organizational functioning without the requisite evidence
      base. Medicine is a unique organizational environment in which the health of
      physicians may be a significant risk factor for inadequate patient safety and
      suboptimal care. Globally, physicians are reporting increasing levels of job
      burnout, especially among younger physicians in training. Not surprisingly,
      higher levels of physician burnout are associated with suboptimal care for
      patients and medical error, as well as maladaptive coping strategies among
      physicians that serve to exacerbate the former. This review is a scoping analysis
      of the existing literature to address the central question: is there a
      relationship between organizational leadership and physician well-being? The
      objectives of the review are as follows: 1) identify the degree to which
      physician health is under threat; 2) evaluate the evidence linking leadership
      with physician well-being; 3) identify alternative ways to approach the problem;
      and 4) outline avenues for future research. Finally, enhancing progress in the
      field is discussed in the contexts of theory, methodology, and impact.

PMID- 29355196
TI  - The association between neighbourhoods and educational achievement, a systematic
      review and meta-analysis.
AB  - Many studies have examined the effects of neighbourhoods on educational outcomes.
      The results of these studies are often conflicting, even if the same independent
      variables (such as poverty, educational climate, social disorganisation, or
      ethnic composition) are used. A systematic meta-analysis may help to resolve this
      lack of external validity. We identified 5516 articles from which we selected 88
      that met all of the inclusion criteria. Using meta-regression, we found that the
      relation between neighbourhoods and individual educational outcomes is a function
      of neighbourhood poverty, the neighbourhood's educational climate, the proportion
      of ethnic/migrant groups, and social disorganisation in the neighbourhood. The
      variance in the findings from different studies can partly be explained by the
      sampling design and the type of model used in each study. More important is the
      use of control variables (school, family SES, and parenting variables) in
      explaining the variation in the strength of neighbourhood effects.

PMID- 29355197
TI  - Improving health care quality and safety: the role of collective learning.
AB  - Despite decades of effort to improve quality and safety in health care, this goal
      feels increasingly elusive. Successful examples of improvement are infrequently
      replicated. This scoping review synthesizes 76 empirical or conceptual studies
      (out of 1208 originally screened) addressing learning in quality or safety
      improvement, that were published in selected health care and management journals
      between January 2000 and December 2014 to deepen understanding of the role that
      collective learning plays in quality and safety improvement. We categorize
      learning activities using a theoretical model that shows how leadership and
      environmental factors support collective learning processes and practices, and in
      turn team and organizational improvement outcomes. By focusing on quality and
      safety improvement, our review elaborates the premise of learning theory that
      leadership, environment, and processes combine to create conditions that promote
      learning. Specifically, we found that learning for quality and safety improvement
      includes experimentation (including deliberate experimentation, improvisation,
      learning from failures, exploration, and exploitation), internal and external
      knowledge acquisition, performance monitoring and comparison, and training.
      Supportive learning environments are characterized by team characteristics like
      psychological safety, appreciation of differences, openness to new ideas social
      motivation, and team autonomy; team contextual factors including learning
      resources like time for reflection, access to knowledge, organizational
      capabilities; incentives; and organizational culture, strategy, and structure;
      and external environmental factors including institutional pressures,
      environmental dynamism and competitiveness and learning collaboratives. Lastly
      learning in the context of quality and safety improvement requires leadership
      that reinforces learning through actions and behaviors that affect people, such
      as coaching and trust building, and through influencing contextual factors,
      including providing resources, developing culture, and taking strategic actions
      that support improvement. Our review highlights the importance of leadership in
      both promoting a supportive learning environment and implementing learning
      processes.

PMID- 29355198
TI  - Overcoming difficult conversations in clinical supervision.
AB  - Background: Clinical supervisors are responsible for managing many facets of
      clinical learning and face a range of challenges when the need for "difficult"
      conversations arises, including the need to manage conflict and relationships.
      Methods: Spotlight on Conversations Workshop was developed to improve the
      capacity of clinical supervisors to engage in difficult conversations. They were
      designed to challenge the mindset of clinical supervisors about difficult
      conversations with students, the consequences of avoiding difficult
      conversations, and to offer activities for practicing difficult conversations.
      Preworkshop, postworkshop, and 4-month follow-up evaluations assessed
      improvements in knowledge, intent to improve, and confidence along with workshop
      satisfaction. Results: Nine workshops were delivered in a range of locations
      across Victoria, Australia, involving a total of 117 clinical supervisors.
      Preworkshop evaluations illustrated that more than half of the participants had
      avoided up to two difficult conversations in the last month in their workplace.
      Postworkshop evaluation at 4 months showed very high levels of satisfaction with
      the workshop's relevancy, content, and training, as well as participants'
      intention to apply knowledge and skills. Also shown were significant changes in
      participants' confidence to have difficult conversations not only with students
      but also with other peers and colleagues. In follow-up in-depth interviews with
      20 of the 117 participants, 75% said they had made definite changes in their
      practice because of what they learned in the workshop and another 10% said they
      would make changes to their practice, but had not had the opportunity yet to do
      so. Conclusion: We conclude that the Spotlight on Conversations Workshop can
      improve the clinical supervisor-student relationship as well as build general
      difficult conversation capacity for a range of stakeholders in clinical settings.

PMID- 29355199
TI  - Innovative physical therapy practice: a qualitative verification of factors that
      support diffusion of innovation in outpatient physical therapy practice.
AB  - Background and purpose: New ideas, methods, and technologies spread through
      cultures through typical patterns described by diffusion of innovation (DOI)
      theory. Professional cultures, including the physical therapy profession, have
      distinctive features and traditions that determine the adoption of practice
      innovation. The Consolidated Framework for Implementation Research (CFIR)
      proposes a framework of innovation implementation specific to health care
      services. While the CFIR has been applied to medical and nursing practice, it has
      not been extended to rehabilitation professions. The purpose of this qualitative
      study was to verify the CFIR factors in outpatient physical therapy practice.
      Design: Through a nomination process of area rehabilitation managers and area
      directors of clinical education, 2 exemplar, outpatient, privately owned physical
      therapy clinics were identified as innovation practices. A total of 18 physical
      therapists (PTs), including 3 owners and a manager, participated in the study.
      Methods: The 2 clinics served as case studies within a qualitative approach of
      directed content analysis. Data were collected through observation, spontaneous,
      unstructured questioning, workflow analysis, structured focus group sessions, and
      artifact analysis including clinical documents. Focus group data were
      transcribed. All the data were analyzed and coded among 4 investigators. Results:
      Through data analysis and alignment with literature in DOI theory in health care
      practice, the factors that determine innovation adoption were verified. The
      phenomena of implementation in PT practice are largely consistent with models of
      implementation in health care service. Within the outpatient practices studied,
      patient-centered care and collaborative learning were foundational elements to
      diffusion of an innovation. Conclusion: Innovation in outpatient physical therapy
      practice can be understood as a social process situated within the culture of the
      physical therapy professional that follows predictable patterns that strongly
      align with DOI theory and the CFIR.

PMID- 29355200
TI  - Developing compassionate leadership in health care: an integrative review.
AB  - Compassionate health care is universally valued as a social and moral good to be
      upheld and sustained. Leadership is considered pivotal for enabling the
      development and preservation of compassionate health care organizations.
      Strategies for developing compassionate health care leadership in the complex,
      fast-moving world of today will require a paradigm shift from the prevalent
      dehumanizing model of the organization as machine to one of the organizations as
      a living complex adaptive system. It will also require the abandonment of
      individualistic, heroic models of leadership to one of shared, distributive, and
      adaptive leadership. "Command and control" leadership, accompanied by stifling
      regulation, rigid prescriptions, coercive punishments, and/or extrinsic rewards,
      infuses fear into the system with consequent disempowerment and disunity within
      the workforce, and the attrition of innovation and compassion. It must be
      eschewed. Instead, leadership should be developed throughout the organization
      with collective holistic learning strategies combined with high levels of staff
      support and engagement. Culture and leadership are interdependent and
      synergistic; their codevelopment needs to be grounded in a sophisticated,
      scientifically based account of human nature held within a coherent philosophical
      framework reflected by modern organizational and leadership theories. Developing
      leadership for compassionate care requires acknowledging and making provision for
      the difficulties and challenges of working in an anxiety-laden context. This
      means providing appropriate training and well-being programs, sustaining high
      levels of trust and mutually supportive interpersonal connections, and fostering
      the sharing of knowledge, skills, and workload across silos. It requires enabling
      people to experiment without fear of reprisal, to reflect on their work, and to
      view errors as opportunities for learning and improvement. Tasks and relational
      care need to be integrated into a coherent unity, creating space for real dialog
      between patients, clinicians, and managers, so that together they can cocreate
      ways to flourish in the context of illness and dying.

PMID- 29355202
TI  - Why continuous discussion can promote the consensus of opinions?
AB  - Why group opinions tend to be converged through continued communication,
      discussion and interactions? Under the framework of the social influence network
      model, we rigorously prove that the group consensus is almost surely within
      finite steps. This is a quite certain result, and reflects the real-world common
      phenomenon. In addition, we give a convergence time lower bound. Although our
      explanations are purely based on mathematic deduction, it shows that the latent
      social influence structure is the key factor for the persistence of disagreement
      and formation of opinions convergence or consensus in the real world social
      system.

PMID- 29355201
TI  - Public health policies to encourage healthy eating habits: recent perspectives.
AB  - There is an urgent need to address unhealthy dietary patterns at the population
      level. Poor diet and physical inactivity are key drivers of the obesity pandemic,
      and they are among the leading causes of preventable death and disability in
      nearly every country in the world. As countries grapple with the growing obesity
      prevalence, many innovative policy options to reduce overeating and improve diet
      quality remain largely unexplored. We describe recent trends in eating habits and
      consequences for public health, vulnerabilities to unhealthy eating, and the role
      for public health policies. We reviewed recent public health policies to promote
      healthier diet patterns, including mandates, restrictions, economic incentives,
      marketing limits, information provision, and environmental defaults.

PMID- 29355203
TI  - Barriers and facilitators of Canadian quality and safety teams: a mixed-methods
      study exploring the views of health care leaders.
AB  - Background: Health care organizations are utilizing quality and safety (QS) teams
      as a mechanism to optimize care. However, there is a lack of evidence-informed
      best practices for creating and sustaining successful QS teams. This study aimed
      to understand what health care leaders viewed as barriers and facilitators to
      establishing/implementing and measuring the impact of Canadian acute care QS
      teams. Methods: Organizational senior leaders (SLs) and QS team leaders (TLs)
      participated. A mixed-methods sequential explanatory design included surveys
      (n=249) and interviews (n=89). Chi-squared and Fisher's exact tests were used to
      compare categorical variables for region, organization size, and leader position.
      Interviews were digitally recorded and transcribed for constant comparison
      analysis. Results: Five qualitative themes overlapped with quantitative data: (1)
      resources, time, and capacity; (2) data availability and information technology;
      (3) leadership; (4) organizational plan and culture; and (5) team composition and
      processes. Leaders from larger organizations more often reported that clear
      objectives and physician champions facilitated QS teams (p<0.01). Fewer Eastern
      respondents viewed board/senior leadership as a facilitator (p<0.001), and fewer
      Ontario respondents viewed geography as a barrier to measurement (p<0.001). TLs
      and SLs differed on several factors, including time to meet with the team, data
      availability, leadership, and culture. Conclusion: QS teams need strong,
      committed leaders who align initiatives to strategic directions of the
      organization, foster a quality culture, and provide tools teams require for their
      work. There are excellent opportunities to create synergy across the country to
      address each organization's quality agenda.

PMID- 29355204
TI  - What are the effective ways to translate clinical leadership into health care
      quality improvement?
AB  - The presence and/or absence of effective leaders in health care can have a stark
      consequence on the quality and outcomes of care. The delivery of safe, quality,
      compassionate health care is dependent on having effective clinical leaders at
      the frontline. In light of the Kirkup and Francis reports, this article explores
      some ways of translating clinical leadership into health care quality
      improvement. This is achieved by exploring what is clinical leadership and why
      and how this is important to health care quality improvement, clinical
      leadership, and a duty of candor, along with the importance clinical leadership
      plays in the provision of quality care improvement and outcomes. Clinical leaders
      are not predefined roles but emerge from the complex clinical setting by gaining
      an acquired expertise and from how they then internalize this to develop and
      facilitate sound relationships within a team. Clinical leaders are effective in
      facilitating innovation and change through improvement. This is achieved by
      recognizing, influencing, and empowering individuals through effective
      communication in order to share and learn from and with each other in practice.
      The challenge for health care organizations in regard to creating organizational
      cultures where a duty of candor exists is not to reinvent the wheel by turning
      something that is simple into something complex, which can become confusing to
      health care workers, patients, and the public. By focusing on the clinical
      leader's role and responsibilities we would argue they play a crucial and pivotal
      role in influencing, facilitating, supporting, and monitoring that this duty of
      candor happens in practice. This may be possible by highlighting where and how
      the duty of candor can be aligned within existing clinical governance frameworks.

PMID- 29355205
TI  - An adverse event in a well-established cervical cancer screening program: an
      observational study of 19,000 females unsubscribed to the program.
AB  - Introduction: In Denmark, an organized approach to cervical cancer screening has
      had national coverage since 1998. However, in 2013, it was discovered that 19,000
      females had been unsubscribed from the Danish National Cervical Cancer Screening
      Program and had thus not received invitations or reminders as recommended by the
      health authorities. The study aims to report the essence of this adverse event
      and describe the outcomes of reestablishing invitations in terms of participation
      rates and screening results. Furthermore, patient compensations to affected
      females diagnosed with cervical cancer and coverage in the mass media was
      reported. Methods: An observational study based on information from the Danish
      Pathology Databank, the Department of Public Health Programs, and Infomedia (a
      Danish database of media coverage) was carried out. Results: A total of 19,106
      females were affected. Of those still in the screening age, 37.7% had been tested
      within 3 years or 5 years despite not receiving any invitation. A total of 21.6%
      reconfirmed their status as unsubscribed. Of the remaining females, 55.6% were
      tested within a year, and 94.6% of these test results were normal. Among females
      aged >64 years, 12.7% accepted the offer of a final screening test. Totally, 90%
      of these tests were normal. Nineteen females diagnosed with cervical cancer were
      compensated by the Danish Patient Compensation Association with a total of
      ?693,000, ranging from ?8,900 to ?239,700. Coverage of cervical cancer screening
      in the mass media increased from 25 items in the 3 months prior to this adverse
      event to 590 items in the month when it became public. Conclusion: Even though
      more than one-third of the affected females were tested despite not receiving
      regular invitations to participate in the screening program, lacking invitations
      were ranked alongside other adverse events in the health care system if cancer
      diagnoses were delayed.

PMID- 29355206
TI  - Detection of strong attractors in social media networks.
AB  - Background: Detection of influential actors in social media such as Twitter or
      Facebook plays an important role for improving the quality and efficiency of work
      and services in many fields such as education and marketing. Methods: The work
      described here aims to introduce a new approach that characterizes the influence
      of actors by the strength of attracting new active members into a networked
      community. We present a model of influence of an actor that is based on the
      attractiveness of the actor in terms of the number of other new actors with which
      he or she has established relations over time. Results: We have used this concept
      and measure of influence to determine optimal seeds in a simulation of influence
      maximization using two empirically collected social networks for the underlying
      graphs. Conclusions: Our empirical results on the datasets demonstrate that our
      measure stands out as a useful measure to define the attractors comparing to the
      other influence measures.

PMID- 29355207
TI  - Text normalization for named entity recognition in Vietnamese tweets.
AB  - Background: Named entity recognition (NER) is a task of detecting named entities
      in documents and categorizing them to predefined classes, such as person,
      location, and organization. This paper focuses on tweets posted on Twitter. Since
      tweets are noisy, irregular, brief, and include acronyms and spelling errors, NER
      in those tweets is a challenging task. Many approaches have been proposed to deal
      with this problem in tweets written in English, Germany, Chinese, etc., but none
      for Vietnamese tweets. Methods: We propose a method that normalizes a tweet
      before taking as an input of a learning model for NER in Vietnamese tweets. The
      normalization step detects spelling errors in a tweet and corrects them using an
      improved Dice's coefficient or n-grams. A Support Vector Machine learning
      algorithm is employed to learn a classifier using six different types of
      features. Results and Conclusion: We train our method on a training set
      consisting of more than 40,000 named entities and evaluate it on a testing set
      consisting of 3,186 named entities. The experimental results showed that our
      system achieves state-of-the-art performance with F1 score of 82.13%.

PMID- 29355209
TI  - Tenure mix: apart or together? Home-making practices and belonging in a Dutch
      street.
AB  - This paper discusses home-making practices and senses of belonging in a street in
      a disadvantaged neighbourhood in the south of the Netherlands. The local tenure
      mix of tenants and owner-occupiers offers insight into the role class and
      ethnicity play in social mixing. Therefore, attention is paid to narratives and
      the informal organisation of different living spaces and territory-making
      practices. Here, the domestic space could be experienced as a vehicle of intimacy
      and sociability, or conversely as encouraging alienation. Such practices, in
      combination with length of stay result in mechanisms of inclusion and exclusion.
      The insights derived from this study will contribute to the theoretical
      discussion on home-making practices and belonging.

PMID- 29355210
TI  - Buildings behaving badly: a behavioral experiment on how different motivational
      frames influence residential energy label adoption in the Netherlands.
AB  - Heating buildings contributes to approximately 36 % of Europe's energy demand and
      several EU member states have adopted mandatory energy labels to improve energy
      efficiency by promoting home weatherization investments. This paper focuses on
      the perception of the energy label for residential buildings in the Netherlands
      and the role of different frames (egoistic, biospheric and social norms and
      neutral frames) in motivating adoption of energy labels for housing. We used a
      behavioral email experiment and an online survey to investigate these
      motivational factors. We find that biospheric frames are weaker than the other
      three motivational frames in terms of engaging interest in the energy label, but
      that the biospheric frame results in higher willingness to pay (WTP) for the
      energy label. We also find that age (rather than income) correlates with higher
      WTP for home energy labels.

PMID- 29355211
TI  - Real-time topic-aware influence maximization using preprocessing.
AB  - Background: Influence maximization is the task of finding a set of seed nodes in
      a social network such that the influence spread of these seed nodes based on
      certain influence diffusion model is maximized. Topic-aware influence diffusion
      models have been recently proposed to address the issue that influence between a
      pair of users are often topic-dependent and information, ideas, innovations etc.
      being propagated in networks are typically mixtures of topics. Methods: In this
      paper, we focus on the topic-aware influence maximization task. In particular, we
      study preprocessing methods to avoid redoing influence maximization for each
      mixture from scratch. Results: We explore two preprocessing algorithms with
      theoretical justifications. Conclusions: Our empirical results on data obtained
      in a couple of existing studies demonstrate that one of our algorithms stands out
      as a strong candidate providing microsecond online response time and competitive
      influence spread, with reasonable preprocessing effort.

PMID- 29355212
TI  - Ottawa Model of Implementation Leadership and Implementation Leadership Scale:
      mapping concepts for developing and evaluating theory-based leadership
      interventions.
AB  - Purpose: Leadership in health care is instrumental to creating a supportive
      organizational environment and positive staff attitudes for implementing evidence
      based practices to improve patient care and outcomes. The purpose of this study
      is to demonstrate the alignment of the Ottawa Model of Implementation Leadership
      (O-MILe), a theoretical model for developing implementation leadership, with the
      Implementation Leadership Scale (ILS), an empirically validated tool for
      measuring implementation leadership. A secondary objective is to describe the
      methodological process for aligning concepts of a theoretical model with an
      independently established measurement tool for evaluating theory-based
      interventions. Methods: Modified template analysis was conducted to deductively
      map items of the ILS onto concepts of the O-MILe. An iterative process was used
      in which the model and scale developers (n=5) appraised the relevance, conceptual
      clarity, and fit of each ILS items with the O-MILe concepts through individual
      feedback and group discussions until consensus was reached. Results: All 12 items
      of the ILS correspond to at least one O-MILe concept, demonstrating compatibility
      of the ILS as a measurement tool for the O-MILe theoretical constructs.
      Conclusion: The O-MILe provides a theoretical basis for developing implementation
      leadership, and the ILS is a compatible tool for measuring leadership based on
      the O-MILe. Used together, the O-MILe and ILS provide an evidence- and theory
      based approach for developing and measuring leadership for implementing evidence
      based practices in health care. Template analysis offers a convenient approach
      for determining the compatibility of independently developed evaluation tools to
      test theoretical models.

PMID- 29355213
TI  - Correction: Therapeutic potential of omega-3 fatty acids supplementation in a
      mouse model of dry macular degeneration.
AB  - [This corrects the article DOI: 10.1136/bmjophth-2016-000056.][This corrects the
      article DOI: 10.1136/bmjophth-2016-000056.].

PMID- 29355214
TI  - Informed consent in field trials of gene-drive mosquitoes.
AB  - The US National Academies' (NAS) recent report 'Gene Drives on the Horizon:
      Advancing Science, Navigating Uncertainty, and Aligning Research with Public
      Values' examines the requirements of responsible conduct in research involving
      gene drives in non-human organisms. Many of the complex ethical issues raised by
      the introduction of gene drive technologies for mosquito population control have
      been anticipated during the development and field-testing of earlier-generation
      genetic engineering approaches with mosquitoes. One issue-the requirement for
      informed consent in field trials-is not addressed explicitly in the NAS' report.
      Some commentators have presumed that informed consent should play a role as a
      protection for research participants in studies of genetically modified
      mosquitoes. Others have argued that there are no human subjects of field trials,
      so the informed consent requirement does not apply. It is both ethically and
      practically important that these presumptions are adequately scrutinized to
      ensure that any applications of informed consent in these trials are properly
      justified. We argue that informed consent from individual research participants
      in gene drive trials may be required: (1) when blood and other forms of clinical
      data are collected from them, as will likely be the case in some studies
      involving epidemiological endpoints, such as the incidence of new infections with
      dengue and malaria; (2) when they participate in social science and/or behavioral
      research involving the completion of surveys and questionnaires; or (3) when
      their home or property is accessed and the location recorded as a spatial
      variable for the release or collection of mosquitoes because the precise location
      of the household is important for entomological reasons and these data constitute
      identifiable private information at the household level. Importantly, most
      regulations and guidelines allow these requirements to be waived or modified, to
      various degrees, according to the judgment of Institutional Review Boards.

PMID- 29355215
TI  - Advancing a conceptual model to improve maternal health quality: The Person
      Centered Care Framework for Reproductive Health Equity.
AB  - Background: Globally, substantial health inequities exist with regard to
      maternal, newborn and reproductive health. Lack of access to good quality care
      across its many dimensions-is a key factor driving these inequities. Significant
      global efforts have been made towards improving the quality of care within
      facilities for maternal and reproductive health. However, one critically
      overlooked aspect of quality improvement activities is person-centered care. Main
      body: The objective of this paper is to review existing literature and theories
      related to person-centered reproductive health care to develop a framework for
      improving the quality of reproductive health, particularly in low and middle
      income countries. This paper proposes the Person-Centered Care Framework for
      Reproductive Health Equity, which describes three levels of interdependent
      contexts for women's reproductive health: societal and community determinants of
      health equity, women's health-seeking behaviors, and the quality of care within
      the walls of the facility. It lays out eight domains of person-centered care for
      maternal and reproductive health. Conclusions: Person-centered care has been
      shown to improve outcomes; yet, there is no consensus on definitions and measures
      in the area of women's reproductive health care. The proposed Framework reviews
      essential aspects of person-centered reproductive health care.

PMID- 29355216
TI  - Clustering 1-dimensional periodic network using betweenness centrality.
AB  - Background: While the temporal networks have a wide range of applications such as
      opportunistic communication, there are not many clustering algorithms
      specifically proposed for them. Methods: Based on betweenness centrality for
      periodic graphs, we give a clustering pseudo-polynomial time algorithm for
      temporal networks, in which the transit value is always positive and the least
      common multiple of all transit values is bounded. Results: Our experimental
      results show that the centrality of networks with 125 nodes and 455 edges can be
      efficiently computed in 3.2 s. Not only the clustering results using the infinite
      betweenness centrality for this kind of networks are better, but also the nodes
      with biggest influences are more precisely detected when the betweenness
      centrality is computed over the periodic graph. Conclusion: The algorithm
      provides a better result for temporal social networks with an acceptable running
      time.

PMID- 29355218
TI  - Connecting physical and social dimensions of place attachment: What can we learn
      from attachment to urban recreational spaces?
AB  - This paper is concerned with the ways in which people form attachments to
      recreational spaces. More specifically it examines the relationship between
      recreational spaces associated with sporting activity in urban neighbourhoods and
      place attachment. The focus is on the ways in which changes to these spaces
      exposes the affective bonds between people and their surroundings. The paper
      applies a qualitative methodology, namely focus groups and photo elicitation, to
      the case study of Parkhead, a neighbourhood in the East End of Glasgow. Parkhead
      has historically been subjected to successive waves of redevelopment as a result
      of deindustrialization in the late twentieth century. More recently redevelopment
      associated with the 2014 Commonwealth Games involved further changes to
      neighbourhood recreational spaces, including refurbishing of existing sports
      facilities and building new ones. This paper reflects on the cumulative impacts
      of this redevelopment to conclude (a) that recreational sports spaces provoke
      multi-layered and complex attachments that are inextricably connected to both
      temporal and spatial narratives and (b) that research on neighbourhood
      recreational spaces can develop our understanding of the intricate relationship
      between the social and physical dimensions of place attachment.

PMID- 29355219
TI  - The continued retreat of non-profit housing providers in the Netherlands.
AB  - After the abolishment of object subsidies for housing construction and renovation
      in the mid 1990s, Dutch housing associations, the main non-profit housing
      providers in the country, heavily relied on market activities, such as selling
      homes to owner occupiers, to generate income for their social activities and to
      contribute to urban development policies. This worked well, which was one of the
      main reasons that these housing providers could adopt a wide field of operations,
      including not only the management and development of affordable housing for low
      income groups, but also housing in other market segments, plus activities
      regarding care, welfare, local economy, employment and education. Recent economic
      and political developments, however, have caused housing associations to return
      on this path. Central in this paper is a research among Dutch housing
      associations about their values, strategic positioning and strategies. The
      research was executed in two waves (conducted in 2010/2011 and in 2013/2014,
      respectively), each consisting of a panel survey and interviews with selected
      panellists. This paper presents the results of the second wave. It is expected
      that after the first wave of the research, new regulations, such as the national
      implementation of European rules on state support and the introduction of a new
      property tax, have resulted in a further retreat from non-social housing
      activities. The analysis shows that this is indeed the case, but that the main
      shifts in priorities have not taken place directly after the credit crunch, but
      in later years.

PMID- 29355220
TI  - The imperative of culture: a quantitative analysis of the impact of culture on
      workforce engagement, patient experience, physician engagement, value-based
      purchasing, and turnover.
AB  - Current uncertainty for the future of the health care landscape is placing an
      increasing amount of pressure on leadership teams to be prepared to steer their
      organization forward in a number of potential directions. It is commonly
      recognized among health care leaders that culture will either enable or disable
      organizational success. However, very few studies empirically link culture to
      health care-specific performance outcomes. Nearly every health care organization
      in the US specifies its cultural aspirations through mission and vision
      statements and values. Ambitions of patient-centeredness, care for the community,
      workplace of choice, and world-class quality are frequently cited; yet, little
      definitive research exists to quantify the importance of building high-performing
      cultures. Our study examined the impact of cultural attributes defined by a
      culture index (Cronbach's alpha = 0.88) on corresponding performance with key
      health care measures. We mapped results of the culture index across data sets,
      compared results, and evaluated variations in performance among key indicators
      for leaders. Organizations that perform in the top quartile for our culture index
      statistically significantly outperformed those in the bottom quartile on all but
      one key performance indicator tested. The culture top quartile organizations
      outperformed every domain for employee engagement, physician engagement, patient
      experience, and overall value-based purchasing performance with statistical
      significance. Culture index top quartile performers also had a 3.4% lower
      turnover rate than the bottom quartile performers. Finally, culture index top
      quartile performers earned an additional 1% on value-based purchasing. Our
      findings demonstrate a meaningful connection between performance in the culture
      index and organizational performance. To best impact these key performance
      outcomes, health care leaders should pay attention to culture and actively steer
      workforce engagement in attributes that represent the culture index, such as
      treating patients as valued customers, having congruency between employee and
      organizational values, promoting employee pride, and encouraging the feeling that
      being a member of the organization is rewarding, in order to leverage culture as
      a competitive advantage.

PMID- 29355222
TI  - Building an urban 'renaissance': fragmented services and the production of
      inequality in Greater Downtown Detroit.
AB  - Downtown Detroit has been undergoing a renaissance in recent years which is in
      stark contrast to the economic and social situation in much of the rest of the
      city. This renaissance has been taking place despite the city's ability to
      provide good municipal services such as streetlights, security, public space and
      transport. This article focuses on how four areas which constitute part of
      Greater Downtown Detroit have relied on different combinations of actors to
      create and provide the services and amenities deemed necessary for capital
      investment and middle-class consumption. Each area has its own initiatives and
      actors who implement them, further fragmenting the city between its core and
      periphery. Renewed public spaces, private police forces and resident initiatives
      in middle-class neighborhoods have been created to serve specific needs of the
      small areas they serve. Rather than being unique, Detroit is an extreme example
      of fragmented and polarized urbanism which is part and parcel of contemporary
      cities. We argue that rather than passively reflecting existing socio-spatial
      divides, these private initiatives in Greater Downtown Detroit actively
      contribute to the production of sociospatial inequalities across the city.

PMID- 29355223
TI  - A hashtag recommendation system for twitter data streams.
AB  - Background: Twitter has evolved into a powerful communication and information
      sharing tool used by millions of people around the world to post what is
      happening now. A hashtag, a keyword prefixed with a hash symbol (#), is a feature
      in Twitter to organize tweets and facilitate effective search among a massive
      volume of data. In this paper, we propose an automatic hashtag recommendation
      system that helps users find new hashtags related to their interests on-demand.
      Methods: For hashtag ranking, we propose the Hashtag Frequency-Inverse Hashtag
      Ubiquity (HF-IHU) ranking scheme, which is a variation of the well-known TF-IDF,
      that considers hashtag relevancy, as well as data sparseness which is one of the
      key challenges in analyzing microblog data. Our system is built on top of Hadoop,
      a leading platform for distributed computing, to provide scalable performance
      using Map-Reduce. Experiments on a large Twitter data set demonstrate that our
      method successfully yields relevant hashtags for user's interest and that
      recommendations are more stable and reliable than ranking tags based on tweet
      content similarity. Results and conclusions: Our results show that HF-IHU can
      achieve over 30 % hashtag recall when asked to identify the top 10 relevant
      hashtags for a particular tweet. Furthermore, our method out-performs kNN, k
      popularity, and Naive Bayes by 69, 54, and 17 %, respectively, on recall of the
      top 200 hashtags.

PMID- 29355224
TI  - Rationale and design of a multi-center, open-label, randomised clinical trial
      comparing HIV incidence and contraceptive benefits in women using three commonly
      used contraceptive methods (the ECHO study).
AB  - BACKGROUND: In vitro, animal, biological and observational clinical studies
      suggest that some hormonal methods, particularly depot medroxyprogesterone
      acetate - DMPA, may increase women's risk of HIV acquisition. DMPA is the most
      common contraceptive used in many countries worst affected by the HIV epidemic.
      To provide robust evidence for contraceptive decision-making among women,
      clinicians and planners, we are conducting the Evidence for Contraceptive Options
      and HIV Outcomes (ECHO) study in four countries with high HIV incidence and DMPA
      use: Kenya, South Africa, Swaziland, and Zambia (Clinical Trials.gov identifier
      NCT02550067). STUDY DESIGN: We randomized HIV negative, sexually active women 16
      35 years old requesting effective contraception and agreeing to participate to
      either DMPA, the copper T 380A intrauterine device or levonorgestrel implant.
      Participants attend a contraception support visit after 1 month and quarterly
      visits thereafter for 12 to 18 months. Participants receive a standard HIV
      prevention package and contraceptive side-effect management at each visit. The
      primary outcome is HIV seroconversion. Secondary outcomes include pregnancy,
      serious adverse events and method discontinuation. The sample size of 7800 women
      provides 80% power to detect a 50% difference in HIV risk between any of the
      three method pairs, assuming 250 incident infections per comparison. Ethical
      considerations: Several WHO consultations have concluded that current evidence on
      HIV risk associated with DMPA is inconclusive and that a randomized trial is
      needed to guide policy, counselling and choice. Previous studies suggest that
      women without a specific contraceptive preference are willing to accept
      randomization to different contraceptive methods. Stringent performance standards
      are monitored by an independent data and safety monitoring board approximately
      every 6 months. The study has been conducted with extensive stakeholder
      engagement. CONCLUSIONS: The ECHO study is designed to provide robust evidence on
      the relative risks (HIV acquisition) and benefits (pregnancy prevention) between
      three effective contraceptive methods.

PMID- 29355226
TI  - Corrigendum: Correction of the IRB Approval Number. Accuracy of Preoperative
      Local Staging of Primary Colorectal Cancer by Using Computed Tomography:
      Reappraisal Based on Data Collected at a Highly Organized Cancer Center.
AB  - [This corrects the article on p. 192 in vol. 33, PMID: 29159167.].

PMID- 29355225
TI  - Detection of Mycobacterium tuberculosis bacilli in bio-aerosols from untreated TB
      patients.
AB  - Background: Tuberculosis (TB) is predominantly an airborne disease. However,
      quantitative and qualitative analysis of bio-aerosols containing the aetiological
      agent, Mycobacterium tuberculosis (Mtb), has proven very challenging. Our
      objective is to sample bio-aerosols from newly diagnosed TB patients for
      detection and enumeration of Mtb bacilli. Methods: We monitored each of 35 newly
      diagnosed, GeneXpert sputum-positive, TB patients during 1 hour confinement in a
      custom-built Respiratory Aerosol Sampling Chamber (RASC). The RASC (a small clean
      room of 1.4m ) incorporates aerodynamic particle size detection, viable and non
      viable sampling devices, real-time CO 2 monitoring, and cough sound-recording.
      Microbiological culture and droplet digital polymerase chain reaction (ddPCR)
      were used to detect Mtb in each of the bio-aerosol collection devices. Results: 
      Mtb was detected in 27/35 (77.1%) of aerosol samples; 15/35 (42.8%) samples were
      positive by mycobacterial culture and 25/27 (92.96%) were positive by ddPCR.
      Culturability of collected bacilli was not predicted by radiographic evidence of
      pulmonary cavitation, sputum smear positivity, or cough rate. Mtb was detected on
      all viable cascade impactor stages with a peak at aerosol sizes 2.0-3.5MUm. This
      suggests a median of 0.09 CFU/litre of exhaled air (IQR: 0.07 to 0.3 CFU/l) for
      the aerosol culture positives and an estimated median concentration of 4.5x10
      CFU/ml (IQR: 2.9x10 -5.6x10 ) of exhaled particulate bio-aerosol. Conclusions: 
      Mtb was identified in bio-aerosols exhaled by the majority of untreated TB
      patients using the RASC. Molecular detection was more sensitive than
      mycobacterial culture on solid media, suggesting that further studies are
      required to determine whether this reflects a significant proportion of
      differentially detectable  bacilli in these samples.

PMID- 29355227
TI  - Syphilis screening and treatment in pregnant women in Kinshasa, Democratic
      Republic of the Congo and in Lusaka, Zambia: a cross-sectional study.
AB  - Background: Congenital syphilis is associated with perinatal deaths, preterm
      births and congenital malformations. Low rates of syphilis screening during
      pregnancy and treatment of those found seropositive have been reported in the
      Democratic Republic of the Congo (DRC) and Zambia. We report the rates on
      antenatal syphilis screening, the seroprevalence of syphilis infection, and the
      frequency of antibiotic treatment in pregnant women screened positive for
      syphilis during their attendance at antenatal care (ANC) clinics in Kinshasa, DRC
      and Lusaka, Zambia. Methods: Women attending their first ANC were enrolled
      consecutively during a 9-month period in 16 and 13 ANC clinics in Kinshasa and
      Lusaka respectively, in the context of the baseline period of a cluster trial.
      Study personnel collected data on women's characteristics, the syphilis screening
      practices, the test results, and the frequency of treatment, that were done under
      routine ANC conditions and registered in the clinic records. Results 4,153 women
      in Kinshasa and 18,097 women in Lusaka were enrolled. The frequency of screening
      at the first visit was 59.7% (n= 2,479) in Kinshasa, and 27.8% (n=5,025) in
      Lusaka. Screening test availability varied. In the periods in which tests were
      available the screening rates were 92.8% in Kinshasa and 52.0% in Lusaka. The
      frequency of women screened seropositive was 0.4% (n=10) in Kinshasa and 2.2%
      (n=109) in Lusaka. Respectively, 10% (n=1) and 11.9% (n= 13) among seropositive
      women received treatment at the first visit. Conclusions: The results of the
      study show that screening for syphilis in pregnancy is not universal even when
      supplies are available. Our ongoing trial will evaluate the impact of a
      behavioral intervention on changing health providers' practices to increase
      screening and treatment rates when supplies are available.

PMID- 29355228
TI  - The maximum contraceptive prevalence 'demand curve': guiding discussions on
      programmatic investments.
AB  - Most frameworks for family planning include both access and demand interventions.
      Understanding how these two are linked and when each should be prioritized is
      difficult. The maximum contraceptive prevalence 'demand curve' was created based
      on a relationship between the modern contraceptive prevalence rate (mCPR) and
      mean ideal number of children to allow for a quantitative assessment of the
      balance between access and demand interventions. The curve represents the maximum
      mCPR that is likely to be seen given fertility intentions and related norms and
      constructs that influence contraceptive use. The gap between a country's mCPR and
      this maximum is referred to as the 'potential use gap.' This concept can be used
      by countries to prioritize access investments where the gap is large, and discuss
      implications for future contraceptive use where the gap is small. It is also used
      within the FP Goals model to ensure mCPR growth from access interventions does
      not exceed available demand.

PMID- 29355229
TI  - Cascade source inference in networks: a Markov chain Monte Carlo approach.
AB  - Cascades of information, ideas, rumors, and viruses spread through networks.
      Sometimes, it is desirable to find the source of a cascade given a snapshot of
      it. In this paper, source inference problem is tackled under Independent Cascade
      (IC) model. First, the #P-completeness of source inference problem is proven.
      Then, a Markov chain Monte Carlo algorithm is proposed to find a solution. It is
      worth noting that our algorithm is designed to handle large networks. In
      addition, the algorithm does not rely on prior knowledge of when the cascade
      started. Finally, experiments on real social network are conducted to evaluate
      the performance. Under all experimental settings, our algorithm identified the
      true source with high probability.

PMID- 29355230
TI  - Information fusion-based approach for studying influence on Twitter using belief
      theory.
AB  - Influence in Twitter has become recently a hot research topic, since this micro
      blogging service is widely used to share and disseminate information. Some users
      are more able than others to influence and persuade peers. Thus, studying most
      influential users leads to reach a large-scale information diffusion area,
      something very useful in marketing or political campaigns. In this study, we
      propose a new approach for multi-level influence assessment on multi-relational
      networks, such as Twitter. We define a social graph to model the relationships
      between users as a multiplex graph where users are represented by nodes, and
      links model the different relations between them (e.g., retweets, mentions, and
      replies). We explore how relations between nodes in this graph could reveal about
      the influence degree and propose a generic computational model to assess
      influence degree of a certain node. This is based on the conjunctive combination
      rule from the belief functions theory to combine different types of relations. We
      experiment the proposed method on a large amount of data gathered from Twitter
      during the European Elections 2014 and deduce top influential candidates. The
      results show that our model is flexible enough to to consider multiple
      interactions combination according to social scientists needs or requirements and
      that the numerical results of the belief theory are accurate. We also evaluate
      the approach over the CLEF RepLab 2014 data set and show that our approach leads
      to quite interesting results.

PMID- 29355232
TI  - A game theory-based trust measurement model for social networks.
AB  - Background: In social networks, trust is a complex social network. Participants
      in online social networks want to share information and experiences with as many
      reliable users as possible. However, the modeling of trust is complicated and
      application dependent. Modeling trust needs to consider interaction history,
      recommendation, user behaviors and so on. Therefore, modeling trust is an
      important focus for online social networks. Methods: We propose a game theory
      based trust measurement model for social networks. The trust degree is calculated
      from three aspects, service reliability, feedback effectiveness, recommendation
      credibility, to get more accurate result. In addition, to alleviate the free
      riding problem, we propose a game theory-based punishment mechanism for specific
      trust and global trust, respectively. Results and conclusions: We prove that the
      proposed trust measurement model is effective. The free-riding problem can be
      resolved effectively through adding the proposed punishment mechanism.

PMID- 29355231
TI  - Pre-exposure prophylaxis for HIV-negative persons with partners living with HIV:
      uptake, use, and effectiveness in an open-label demonstration project in East
      Africa.
AB  - Introduction: Pre-exposure prophylaxis (PrEP) can provide high protection against
      HIV infection and is a recommended intervention for HIV-negative persons with
      substantial HIV risk, such as individuals with a partner living with HIV. 
      Demonstration projects of PrEP have been conducted in diverse settings worldwide
      to illustrate practical examples of how PrEP can be delivered.  Methods: We
      evaluated delivery of PrEP for HIV-negative partners within heterosexual HIV
      serodiscordant couples in an open-label demonstration project in East Africa. 
      The delivery model integrated PrEP into HIV treatment services, prioritizing PrEP
      for HIV-negative partners within serodiscordant couples prior to and during the
      first 6 months after the partner living with HIV initiated antiretroviral therapy
      (ART).  We measured adherence to PrEP through medication event monitoring system
      (MEMS) bottle caps and quantification of tenofovir in plasma among a random
      sample of participants. We estimated HIV infections prevented using a
      counterfactual cohort simulated from the placebo arm of a previous PrEP clinical
      trial. Results: We enrolled 1,010 HIV serodiscordant couples that were naive to
      ART and PrEP.  Ninety-seven percent (97%) of HIV-negative partners initiated
      PrEP, and when PrEP was dispensed, objective measures suggest high adherence: 71%
      of HIV-negative participants took >=80% of expected doses, as recorded via MEMS,
      and 81% of plasma samples had tenofovir detected.  A total of 4 incident HIV
      infections were observed (incidence rate=0.24 per 100 person-years), a 95%
      reduction (95% CI 86-98%, p<0.0001) in HIV incidence, relative to estimated HIV
      incidence for the population in the absence of PrEP integrated into HIV treatment
      services.   Conclusions: PrEP uptake and adherence were high and incident HIV was
      rare in this PrEP demonstration project for African HIV-negative individuals
      whose partners were known to be living with HIV.  Delivery of PrEP to HIV
      negative partners within HIV serodiscordant couples was feasible and should be
      prioritized for wide-scale implementation.

PMID- 29355233
TI  - Erratum: Ottawa Model of Implementation Leadership and Implementation Leadership
      Scale: mapping concepts for developing and evaluating theory-based leadership
      interventions [Corrigendum].
AB  - [This corrects the article on p. 15 in vol. 9.].

PMID- 29355234
TI  - Factorization threshold models for scale-free networks generation.
AB  - Background: Several models for producing scale-free networks have been suggested;
      most of them are based on the preferential attachment approach. In this article,
      we suggest a new approach for generating scale-free networks with an alternative
      source of the power-law degree distribution. Methods: The model derives from
      matrix factorization methods and geographical threshold models that were recently
      proven to show good results in generating scale-free networks. We associate each
      node with a vector having latent features distributed over a unit sphere and with
      a weight variable sampled from a Pareto distribution. We join two nodes by an
      edge if they are spatially close and/or have large weights. Results and
      conclusion: The network produced by this approach is scale free and has a power
      law degree distribution with an exponent of 2. In addition, we propose an
      extension of the model that allows us to generate directed networks with tunable
      power-law exponents.

PMID- 29355235
TI  - Optimization problems in correlated networks.
AB  - Background: Solving the shortest path and min-cut problems are key in achieving
      high-performance and robust communication networks. Those problems have often
      been studied in deterministic and uncorrelated networks both in their original
      formulations as well as in several constrained variants. However, in real-world
      networks, link weights (e.g., delay, bandwidth, failure probability) are often
      correlated due to spatial or temporal reasons, and these correlated link weights
      together behave in a different manner and are not always additive, as commonly
      assumed. Methods: In this paper, we first propose two correlated link weight
      models, namely (1) the deterministic correlated model and (2) the (log-concave)
      stochastic correlated model. Subsequently, we study the shortest path problem and
      the min-cut problem under these two correlated models. Results and Conclusions:
      We prove that these two problems are NP-hard under the deterministic correlated
      model, and even cannot be approximated to arbitrary degree in polynomial time.
      However, these two problems are solvable in polynomial time under the
      (constrained) nodal deterministic correlated model, and can be solved by convex
      optimization under the (log-concave) stochastic correlated model.

PMID- 29355236
TI  - Analysis and control of information diffusion dictated by user interest in
      generalized networks.
AB  - The diffusion of useful information in generalized networks, such as those
      consisting of wireless physical substrates and social network overlays is very
      important for theoretical and practical applications. Contrary to previous works,
      we focus on the impact of user interest and its features (e.g., interest
      periodicity) on the dynamics and control of diffusion of useful information
      within such complex wireless-social systems. By considering the impact of
      temporal and topical variations of users interests, e.g., seasonal periodicity of
      interest in summer vacation advertisements which spread more effectively during
      Spring-Summer months, we develop an epidemic-based mathematical framework for
      modeling and analyzing such information dissemination processes and use three
      indicative operational scenarios to demonstrate the solutions and results that
      can be obtained by the corresponding differential equation-based formalism. We
      then develop an optimal control framework subject to the above information
      diffusion modeling that allows controlling the trade-off between information
      propagation efficiency and the associated cost, by considering and leveraging on
      the impact that user interests have on the diffusion processes. By analysis and
      extensive simulations, significant outcomes are obtained on the impact of each
      network layer and the associated interest parameters on the dynamics of useful
      information diffusion. Furthermore, several behavioral properties of the optimal
      control of the useful information diffusion with respect to the number of
      infected/informed nodes and the evolving user interest are shown through analysis
      and verified via simulations. Specifically, a key finding is that low interest
      related diffusion can be aided by utilizing proper optimal controls. Our work in
      this paper paves the way towards this user-centered information diffusion
      framework.

PMID- 29355238
TI  - Lay health advisers: scoping the role and intervention landscape.
AB  - The use of lay health advisers has become an established approach within public
      health, in particular for impact on health inequalities and engaging socially
      excluded groups. Evidence on how differences in terms of the multiple role
      dimensions impact the outcomes of programs is limited. This creates ambiguity for
      decision makers on which roles should be implemented in different contexts for
      different needs. This paper applies realist logic to an inquiry to explore the
      mechanisms that may operate in lay-led intervention models and understand how,
      why, and in what respect these lead to particular outcomes. It draws on a project
      focusing on health-related lifestyle advisers and further insights gained from a
      subsequent related project about outreach with traveler communities. Analysis
      highlights multiple and potentially interacting aspects of lay health-adviser
      roles that may influence their success, including characteristics of lay health
      advisers, characteristics of target populations, purpose or intent of
      interventions, and how advice is given. A model is proposed from which to examine
      the contexts and mechanisms of lay health advisers that may impact outcomes, and
      is subsequently applied to two examples of reported lay health-adviser
      interventions. The combination of skills and characteristics of lay health
      advisers must be considered when planning which interventions might be
      appropriate when targeting specific needs or target populations. Focus only on
      the peer/layperson distinction may overlook other potentially important skills
      and mechanisms of action integral to lay health-adviser roles.

PMID- 29355237
TI  - Erratum: Author Correction: Successful amplification of DNA aboard the
      International Space Station.
AB  - [This corrects the article DOI: 10.1038/s41526-017-0033-9.].

PMID- 29355239
TI  - Collaborative public-private initiatives targeting multidrug-resistant
      tuberculosis (MDR-TB) supported by the Lilly MDR-TB Partnership: experiences in
      2012-2016.
AB  - Since 2003, the Lilly Foundation has supported the noncommercial Lilly MDR-TB
      Partnership, which involves more than 45 local, national, global, and
      nongovernmental organizations and governments. The aim of the Lilly MDR-TB
      Partnership is to achieve significant global impact on multidrug-resistant
      tuberculosis (MDR-TB) by addressing a series of important local health care needs
      in highly affected countries: China, India, Russia, and South Africa. The main
      focus of activities during 2012-2016 was on community needs in primary care.
      Supported projects seek to make meaningful and measurable progress toward global
      and national TB objectives. The partnership programs share an overall conceptual
      approach known as "research, report, advocate", based on the piloting of novel
      approaches on a small scale, with outcomes assessed at early stages. The results
      are analyzed and communicated to governments, health-policy experts, and local
      and national stakeholders, including those in other countries facing similar MDR
      TB challenges. For successful, cost-effective initiatives, the analysis is used
      as support when advocating for the scaling up of initiatives to regional or
      national levels. This article discusses representative examples of projects
      supported by the Lilly MDR-TB Partnership in the time period 2012-2016. The
      examples illustrate the potential for globally informed, locally designed primary
      care collaborations to strengthen health care systems and support TB policies and
      offer observations to inform future health care public-private partnerships.

PMID- 29355240
TI  - Leadership requirements for Lean versus servant leadership in health care: a
      systematic review of the literature.
AB  - As health care organizations face pressures to improve quality and efficiency
      while reducing costs, leaders are adopting management techniques and tools used
      in manufacturing and other industries, especially Lean. Successful Lean leaders
      appear to use a coaching leadership style that shares underlying principles with
      servant leadership. There is little information about specific similarities and
      differences between Lean and servant leaderships. We systematically reviewed the
      literature on Lean leadership, servant leadership, and health care and performed
      a comparative analysis of attributes using Russell and Stone's leadership
      framework. We found significant overlap between the two leadership styles,
      although there were notable differences in origins, philosophy, characteristics
      and behaviors, and tools. We conclude that both Lean and servant leaderships are
      promising models that can contribute to the delivery of patient-centered, high
      value care. Servant leadership may provide the means to engage and develop
      employees to become successful Lean leaders in health care organizations.

PMID- 29355241
TI  - Response to Comment on "Turning Vulcanized Natural Rubber into a Self-Healing
      Polymer: Effect of the Disulfide/Polysulfide Ratio".

PMID- 29355242
TI  - A novel basolateral type IV secretion model for the CagA oncoprotein of
      Helicobacter pylori.
AB  - Intercellular junctions are crucial structural elements for the formation and
      maintenance of epithelial barrier functions to control homeostasis or protect
      against intruding pathogens in humans. Alterations in these complexes represent
      key events in the development and progression of numerous cancers as well as
      multiple infectious diseases. Many bacterial pathogens harbor type IV secretion
      systems (T4SSs), which translocate virulence factors into host cells to hijack
      cellular processes. The pathology of the gastric pathogen and type-I carcinogen
      Helicobacter pylori strongly depends on a T4SS encoded by the cag pathogenicity
      island (cagPAI). This T4SS forms a needle-like pilus and its activity is
      accomplished by the pilus-associated factors CagL, CagI and CagY which target the
      host integrin-beta1 receptor followed by injection of the CagA oncoprotein into
      non-polarized AGS gastric epithelial cells. The finding of a T4SS receptor,
      however, suggested the presence of a sophisticated control mechanism for the
      injection of CagA. In fact, integrins constitute a group of basolateral
      receptors, which are normally absent at apical surfaces of the polarized
      epithelium in vivo. Our new results demonstrate that T4SS-pilus formation during
      H. pylori infection of polarized epithelial cells occurs preferentially at
      basolateral sites, and not at apical membranes (Tegtmeyer et al., 2017). We
      propose a stepwise process how H. pylori interacts with components of
      intercellular tight junctions (TJs) and adherens junctions (AJs), followed by
      contacting integrin-based focal adhesions to disrupt and transform the epithelial
      cell layer in the human stomach. The possible impact of this novel signaling
      cascade on pathogenesis during infection is reviewed.

PMID- 29355243
TI  - Satisfaction among early and mid-career dentists in a metropolitan dental
      hospital in China.
AB  - A growing body of research has examined career satisfaction among dentists using
      a standardized instrument, dentist satisfaction survey (DSS). This project
      examined career satisfaction of early to mid-career dentists in China, a
      population whose career satisfaction, heretofore, has not been studied. This is
      an especially critical time to examine career satisfaction because of health care
      reform measures being implemented in China. A culturally sensitive Chinese
      language version of the DSS (CDSS) was developed and electronically administered
      to 367 early and mid-career dentists in a tertiary dental hospital in Beijing,
      China. One hundred and seventy respondents completed the survey. The average
      total career score was 123, with a range of 82-157. Data analysis showed some
      significant differences in total career score and several subscales based on
      gender, working hours per week, and years in practice. A stepwise regression
      model revealed that two variables predicted total career score: working hours per
      week and gender. Stepwise regression also demonstrated that four subscales
      significantly predicted the overall professional satisfaction subscale score:
      respect, delivery of care, income and patient relations. Implications of these
      results are discussed in light of the health care delivery system and dentist
      career paths in China.

PMID- 29355245
TI  - The Obstacles to Current Extracellular Vesicle-Mediated Drug Delivery Research.
AB  - Extracellular Vesicles (EVs) are nanometer-sized cell-derived membrane vesicles
      that are released by donor cells and play an important role in intercellular
      communication. In this short communication, we discuss the obstacles currently
      faced in EV-mediated drug delivery research. The commonly used vehicle for drug
      delivery in prevalent practice are liposome's which are synthetic vesicles, these
      vesicles commonly interact with serum proteins, macrophages and other innate
      immune response molecules and may be destroyed before they can deliver the drug.
      EVs however have the same membrane compositions and similar cell surface markers
      as the cells from which they are derived which thus prevents interactions or
      provocations of an immune response. In addition, EVs have been used to deliver
      molecules across tight cellular junctions such as the blood brain barrier. This
      has led to an interest in using EVs as a novel method for drug delivery. We
      hereby discuss the potential pitfalls and difficulties that need to be addressed
      before EVs can be used as drug delivery vehicles in pharmacological research.

PMID- 29355246
TI  - Rediscovering Don Swanson: the Past, Present and Future of Literature-Based
      Discovery.
AB  - The late Don R. Swanson was well appreciated during his lifetime as Dean of the
      Graduate Library School at University of Chicago, as winner of the American
      Society for Information Science Award of Merit for 2000, and as author of many
      seminal articles. In this informal essay, I will give my personal perspective on
      Don's contributions to science, and outline some current and future directions in
      literature-based discovery that are rooted in concepts that he developed.

PMID- 29355244
TI  - A game of substrates: replication fork remodeling and its roles in genome
      stability and chemo-resistance.
AB  - During the hours that human cells spend in the DNA synthesis (S) phase of the
      cell cycle, they may encounter adversities such as DNA damage or shortage of
      nucleotides. Under these stresses, replication forks in DNA may experience
      slowing, stalling, and breakage. Fork remodeling mechanisms, which stabilize slow
      or stalled replication forks and ensure their ability to continue or resume
      replication, protect cells from genomic instability and carcinogenesis. Fork
      remodeling includes DNA strand exchanges that result in annealing of newly
      synthesized strands (fork reversal), controlled DNA resection, and cleavage of
      DNA strands. Defects in major tumor suppressor genes BRCA1 and BRCA2, and a
      subset of the Fanconi Anemia genes have been shown to result in deregulation in
      fork remodeling, and most prominently, loss of kilobases of nascent DNA from
      stalled replication forks. This phenomenon has recently gained spotlight as a
      potential marker and mediator of chemo-sensitivity in cancer cells and,
      conversely, its suppression - as a hallmark of acquired chemo-resistance.
      Moreover, nascent strand degradation at forks is now known to also trigger innate
      immune response to self-DNA. An increasingly sophisticated molecular description
      of these events now points at a combination of unbalanced fork reversal and end
      resection as a root cause, yet also reveals the multi-layered complexity and
      heterogeneity of the underlying processes in normal and cancer cells.

PMID- 29355247
TI  - A lentiviral system for efficient knockdown of proteins in neuronal cultures
      [version 1; referees: 2 approved].
AB  - We have devised a protocol for highly efficient and specific knockdown of
      proteins in neuronal cultures. Small hairpin RNAs (shRNAs) are embedded into a
      microRNA (miRNA) context by oligo annealing to create shRNAmiRs, which are
      expressed from within the 3'-UTR of a reporter protein. This reporter
      protein/synthetic miRNA cassette is transferred to a targeting vector and
      lentivirus is produced in HEK-293-T cells following co-transfection of the
      targeting vector with three additional vectors encoding essential lentiviral
      proteins. Mature virus is harvested by collecting culture medium from transfected
      HEK-293-T cells, the virus is purified by centrifugation, and virus titers are
      determined prior to addition to neuronal cultures. Near 100% transduction
      efficiency of cultured hippocampal neurons is routinely observed and allows for
      the population-wide inhibition of target protein expression and the simultaneous
      knockdown of multiple proteins with little or no toxicity. The lentivirus
      generated can be used for protein knockdown in multiple neuronal culture models
      and at a variety of developmental stages. The steps from shRNAmiR design to ready
      to-use virus stocks can be completed in as little as two weeks.

PMID- 29355248
TI  - FAMILY INTERACTION AND SOCIAL STIGMATIZATION OF PEOPLE LIVING WITH HIV AND AIDS
      IN PUERTO RICO.
AB  - This article aims to describe the manifestation of HIV stigma in the family
      context and how this could impact the life of people living with HIV (PLWH). The
      data derive from a larger phenomenological study addressing manifestations of
      stigma in the lives of PLWH when interacting with the health sector. Nine focus
      groups were carried out in 2011 with PLWH (N=67). Eight themes emerged from the
      qualitative analysis. For the purpose of this article, we focus on the categories
      related to family dynamics: the negotiation of disclosure and non-disclosure,
      fear of the HIV virus and family dynamics, and life as a couple. Socio
      demographic information showed that 53% were between 44 to 54 years old, 80% were
      single, 51% were male, 42% did not complete a high school diploma, 82% were
      unemployed. Also, 82% described themselves as religious persons and 41% had lived
      with HIV for 10 years or less. Qualitative results show stigma is still present
      in the family context. PLWH experience fear of disclosure, discrimination, avoid
      initiating families or couple relationships, experience physical and verbal abuse
      from relatives, and even separation from other family members. After more than 30
      years of the ongoing HIV epidemic, stigma is still manifested by family members
      with detrimental social and medical implications for PLWH. Research and
      educational efforts should continue addressing manifestations of stigma among
      family members of PLWH.

PMID- 29355249
TI  - Developing a model for effective leadership in healthcare: a concept mapping
      approach.
AB  - Purpose: Despite increasing awareness of the importance of leadership in
      healthcare, our understanding of the competencies of effective leadership remains
      limited. We used a concept mapping approach (a blend of qualitative and
      quantitative analysis of group processes to produce a visual composite of the
      group's ideas) to identify stakeholders' mental model of effective healthcare
      leadership, clarifying the underlying structure and importance of leadership
      competencies. Methods: Literature review, focus groups, and consensus meetings
      were used to derive a representative set of healthcare leadership competency
      statements. Study participants subsequently sorted and rank-ordered these
      statements based on their perceived importance in contributing to effective
      healthcare leadership in real-world settings. Hierarchical cluster analysis of
      individual sortings was used to develop a coherent model of effective leadership
      in healthcare. Results: A diverse group of 92 faculty and trainees individually
      rank-sorted 33 leadership competency statements. The highest rated statements
      were "Acting with Personal Integrity", "Communicating Effectively", "Acting with
      Professional Ethical Values", "Pursuing Excellence", "Building and Maintaining
      Relationships", and "Thinking Critically". Combining the results from
      hierarchical cluster analysis with our qualitative data led to a healthcare
      leadership model based on the core principle of Patient Centeredness and the core
      competencies of Integrity, Teamwork, Critical Thinking, Emotional Intelligence,
      and Selfless Service. Conclusion: Using a mixed qualitative-quantitative
      approach, we developed a graphical representation of a shared leadership model
      derived in the healthcare setting. This model may enhance learning, teaching, and
      patient care in this important area, as well as guide future research.

PMID- 29355250
TI  - Conceptualizations of clinical leadership: a review of the literature.
AB  - Introduction: Poor patient outcomes in South African maternal health settings
      have been associated with inadequately performing health care providers and poor
      clinical leadership at the point of care. While skill deficiencies among health
      care providers have been largely addressed, the provision of clinical leadership
      has been neglected. In order to develop and implement initiatives to ensure
      clinical leadership among frontline health care providers, a need was identified
      to understand the ways in which clinical leadership is conceptualized in the
      literature. Design: Using the systematic quantitative literature review, papers
      published between 2004 and 2016 were obtained from search engines (Google Scholar
      and EBSCOhost). Electronic databases (CINHAL, PubMed, Medline, Academic Search
      Complete, Health Source: Consumer, Health Source: Nursing/Academic, ScienceDirect
      and Ovid(r)) and electronic journals (Contemporary Nurse, Journal of Research in
      Nursing, Australian Journal of Nursing and Midwifery, International Journal of
      Clinical Leadership) were also searched. Results: Using preselected inclusion
      criteria, 7256 citations were identified. After screening 230 potentially
      relevant full-text papers for eligibility, 222 papers were excluded because they
      explored health care leadership or clinical leadership among health care
      providers other than frontline health care providers. Eight papers met the
      inclusion criteria for the review. Most studies were conducted in high-income
      settings. Conceptualizations of clinical leadership share similarities with the
      conceptualizations of service leadership but differ in focus, with the intent of
      improving direct patient care. Clinical leadership can be a shared
      responsibility, performed by every competent frontline health care provider,
      regardless of the position in the health care system. Conclusion:
      Conceptualizations of clinical leadership among frontline health care providers
      arise mainly from high-income settings. Understanding the influence of context on
      conceptualizations of clinical leadership in middle- and low-income settings may
      be required.

PMID- 29355251
TI  - Synthesis, characterization and Pd(ii)-coordination chemistry of the ligand
      tris(quinolin-8-yl)phosphite. Application in the catalytic aerobic oxidation of
      amines.
AB  - The synthesis and characterization of the ligand tris(quinolin-8-yl)phosphite,
      (P(Oquin)3), are described and its coordination chemistry toward the metal
      precursor [Pd(COD)Cl2] (COD = 1,5-cyclooctadiene, C8H12) is reported. A new
      Pd(ii)-P(Oquin)3 metal complex was isolated and fully characterized
      ([Pd{P(Oquin)3}Cl2]), and its X-ray diffraction analysis shows that the phosphite
      ligand coordinates as a bidentate P-N chelate. This complex is an efficient
      catalyst for the solvent-free mild oxidative coupling of primary amines to imines
      using air as an oxidant, obtaining moderate to good yields (up to 99%) and
      turnover numbers (TONs up to 230). This catalyst can be recovered from the
      reaction mixture and reused in a subsequent run without a significant loss of
      activity. Kinetic measurements of the oxidation of benzylamine suggest that the
      rate law is r = kapp[BnNH2][cat] ([BnNH2] = molar concentration of benzylamine,
      [cat] = molar concentration of [Pd{P(Oquin)3}Cl2], kapp = k[O2]c = 0.756 L mol-1
      h-1 = apparent rate constant). In situ NMR tests were performed to gain some
      insight into the reactivity of the Pd(ii)-P(Oquin)3 complex toward benzylamine.

PMID- 29355252
TI  - Friction induced structural transformations of water monolayers at graphene/Cu
      interfaces.
AB  - Tribological and structural properties of water monolayers confined at interfaces
      between graphene and Cu substrates at cryogenic and room temperatures are
      extensively studied using molecular dynamics simulations and first-principles
      calculations. The frictions caused by the sliding of graphene sheets and
      increasing temperature will reduce the interfacial density of water molecules and
      lead to structural transformations of water monolayers and direct contacts of
      graphene with the underlying Cu substrates. Such changes in water structures give
      rise to higher friction forces and shear strengths at the graphene/Cu interfaces.
      Depending on the water coverage density and temperature, the motions of graphene
      on monolayer water covered Cu exhibit stick-slip and continuous slipping
      behaviors. The strong association of friction characteristics with structural
      transformations of water molecules could be used to unveil interfacial
      information of graphene on water adsorbed metal surfaces.

PMID- 29355253
TI  - On the physics of both surface overcharging and charge reversal at heterophase
      interfaces.
AB  - The conventional paradigm for characterizing surface overcharging and charge
      reversal is based on the so-called Stern layer, in which surface dissociation
      reaction and specific chemical adsorption are assumed to take place. In this
      article, a series of Monte Carlo simulations have been applied to obtain useful
      insights into the underlying physics responsible for these two kinds of anomalous
      phenomena at the interface of two dielectrics, with special emphasis on the case
      of divalent counterions that are more relevant in natural and biological
      environments. At a weakly charged surface, it is found that independent of the
      type of surface charge distribution and the dielectric response of the solution,
      the overcharging event is universally driven by the ion size-asymmetric effect.
      Exceptionally, the overcharging still persists when the surface is highly charged
      but is only restricted to the case of discrete surface charge in a relatively low
      dielectric medium. As compared to the adsorption onto the homogeneously smeared
      charge surface that has the same average affinity for counterions, on the other
      hand, charge reversal under the action of a dielectric response can be
      substantially enhanced in the discrete surface charge representation due to
      strong association of counterions with interfacial groups, and the degree of
      enhancement depends in a nontrivial way on the reduction of the medium dielectric
      constant and the steric effects of finite ion size. Rather interestingly, the
      charge reversal is of high relevance to the overcharging of interfaces because
      the overwhelming interfacial association forces the coions closer to the surface
      due to their smaller size than the counterions. Upon the addition of a monovalent
      salt to the solution, the interfacial association with divalent counterions makes
      surface overcharging and charge reversal widely unaffected, in contrast to the
      prevailing notion that screening of surface charge of a homogeneous nature is
      determined by the competitive effects between size-exclusion effects and
      energetic contributions. Overall, the present work highlights that the complex
      interplay between the electrostatic and steric interactions should be coupled to
      the realistic character of surface charge to establish a faithful description of
      the overcharging and charge reversal at heterophase interfaces.

PMID- 29355254
TI  - Transition states of spin-forbidden reactions.
AB  - Spin-orbit coupling plays an important role in determining the mechanisms and
      kinetics of spin-forbidden reactions and many reactions exhibiting two-state
      reactivity. Spin-orbit coupling can allow the system to change its spin state,
      especially when potential energy surfaces (PESs) of two spin states approach each
      other. Here, we introduce a convenient new approximation method for locating
      stationary points on the lowest mixed-spin potential energy surface along a
      reaction pathway by using density functional calculations. The mixing of
      different spin states is achieved by introducing the spin-orbit coupling into the
      electronic Hamiltonian using a pre-defined coupling constant. Two examples are
      given using the new methodology: (a) a CO association reaction with the
      coordinatively unsaturated Fe(CO)4 complex and (b) an alpha-H elimination
      reaction of a model complex containing W. We computed a Gibbs free energy of
      activation of 2.8 kcal mol-1 for the CO association reaction, which is reasonably
      consistent with the experimentally measured reaction rate. For the H elimination
      reaction, the spin change occurs at a relatively low energy, and the present
      treatment allows one conclude that kinetics of the reaction can be reasonably
      well described without spin-orbit coupling.

PMID- 29355255
TI  - Sensitized near infrared emission through supramolecular d -> f energy transfer
      within an ionic Ru(ii)-Er(iii) pair.
AB  - The newly synthesized ionic triple salt Ru-Er,
      {[RuII(bpy)2(dbim)][ErIII(hfac)4][CF3COO].H2O} (bpy = 2,2'-bipyridine; hfac- =
      hexafluoroacetylacetonate; dbim = 2,2'-dibenzimidazole) exhibits near-infrared
      (NIR) emission at 1535 nm by intermolecular Ru -> Er (d -> f) energy transfer
      across supramolecular interactions when pumped within the Ru(ii) 3MLCT band. It
      is the first such observation for a transition metal-lanthanide ionic pair.

PMID- 29355256
TI  - Heterometallic hexanuclear Ni4M2 (M = Dy, Y) complexes: structure and single
      molecule magnet for the Dy(iii) derivative.
AB  - To achieve a heterometallic single-molecule magnet with novel topologies, two
      isostructural hexanuclear clusters [Ni4Ln2(MU3-OH)2L4(OAc)8].H2O [Ln = Dy, 1; Y,
      2] were prepared from the reactions of 1,3-diamine-2-propanol (HL) with MCl3.6H2O
      (M = Dy, Y) and Ni(OAc)2.4H2O in acetonitrile, in which the studies for 2 with
      the diamagnetic metal ion of Y(iii) are just for further understanding of the
      magnetic properties of 1. Single-crystal X-ray diffraction measurements indicate
      that both heterometallic hexanuclear complexes possess an S-shaped double-pocket
      skeleton with the two M(iii) ions separated by a chair-like Ni4O4 moiety. The
      temperature- and frequency-dependent alternating-current (ac) susceptibility
      measurements under zero dc fields revealed a single-molecule magnet for 1. Its
      magnetic properties can be further understood based on the magnetic analysis of
      2.

PMID- 29355257
TI  - Humidity-responsive phase transition and on-demand UV-curing in a hygroscopic
      polysiloxane-surfactant nanohybrid film.
AB  - We developed a surfactant-directed dynamic hybrid film system containing a
      cationic hygroscopic polysiloxane whose mesostructure is rapidly altered between
      lamellar and hexagonal phases by the change in surrounding humidity.
      Immobilization of one phase is successfully achieved by UV-curing through a
      photoinitiated thiol-ene reaction. This strategy enables the instant activation
      of a curable LLC mesostructure on-demand by humidification from a dormant state
      in a dry atmosphere.

PMID- 29355258
TI  - Analyzing the structure of macromolecules in their native cellular environment
      using hydroxyl radical footprinting.
AB  - Hydroxyl radical footprinting (HRF) has been successfully used to study the
      structure of both nucleic acids and proteins. The method utilizes hydroxyl
      radicals to oxidize solvent accessible sites in macromolecules. In recent years,
      the method has shown some utility for live cell analysis. In this review, we will
      survey the current state of the field for footprinting macromolecules in living
      cells. The field is relatively new, particularly for protein studies, with only a
      few publications on the development and application of HRF on live cells. DNA
      protein interaction sites and information on the secondary and tertiary structure
      of RNA has been characterized. In addition, the conformational changes of
      membrane-spanning channels upon opening and activation have also been studied by
      in-cell HRF. In this review, we highlight examples of these applications.

PMID- 29355259
TI  - Porous CoP nanosheets converted from layered double hydroxides with superior
      electrochemical activity for hydrogen evolution reactions at wide pH ranges.
AB  - Porous materials are widely studied in many applications due to their high
      surface area and rich edge sites. Here, for the first time, we reported a simple
      and convenient method to synthesize porous nanosheets of metal hydroxides by
      selectively etching amphoteric Al in CoAl layered double hydroxides on carbon
      paper (CoAl-LDH/CP), and then convert them into porous cobalt phosphide
      nanosheets on carbon paper (p-CoP/CP) via low temperature phosphidation. In
      contrast to pristine cobalt phosphide nanosheets on carbon paper (CoP/CP), p
      CoP/CP has lower overpotential, Tafel slope and charge transfer resistance as
      well as higher electrochemically active surface area. The excellent
      electrochemical characteristics make it have outstanding catalytic activity and
      stability over the whole pH range. In 1.0 M KOH, the p-CoP/CP only requires an
      overpotential of 57 mV to drive 10 mA cm-2. To achieve the same current density,
      it only needs overpotentials of 39 and 60 mV in 1.0 M H2SO4 and 1.0 M PBS,
      respectively. To our knowledge, it is the best among those nonprecious
      electrocatalysts used for hydrogen evolution in neutral solution. Moreover, this
      catalyst offers good durability over the whole pH range.

PMID- 29355260
TI  - Synthesis of bench-stable solid triorganoindium reagents and reactivity in
      palladium-catalyzed cross-coupling reactions.
AB  - Bench-stable solid triorganoindium compounds have been prepared by coordination
      with 4-(dimethylamino)pyridine (DMAP). The solid R3In(DMAP) complexes are
      obtained from the corresponding solution of R3In in quantitative yield and can be
      stored for up to several weeks. These reagents show excellent reactivity in
      palladium-catalyzed cross-coupling reactions with organic electrophiles.

PMID- 29355261
TI  - 3D printing of graphene-doped target for "matrix-free" laser
      desorption/ionization mass spectrometry.
AB  - We report a graphene-doped resin target fabricated via a 3D printing technique
      for laser desorption/ionization mass spectrometry analysis. The graphene doped in
      the target acts as an inherent laser absorber and ionization promoter, thus
      permitting the direct analysis of samples without adding matrix. This work
      reveals a new strategy for easy designing and fabrication of functional mass
      spectrometry devices.

PMID- 29355263
TI  - Layered gadolinium hydroxides for simultaneous drug delivery and imaging.
AB  - The potential of the layered gadolinium hydroxide (LGdH) [Gd2(OH)5]Cl.yH2O (LGdH
      Cl) for simultaneous drug delivery and magnetic resonance imaging was explored in
      this work. Three non-steroidal anti-inflammatory drugs (diclofenac [dic],
      ibuprofen [ibu], and naproxen [nap]) were intercalated into LGdH-Cl for the first
      time, using three different routes (ion exchange intercalation, coprecipitation,
      and exfoliation-self-assembly). X-ray diffraction, elemental microanalysis and IR
      spectroscopy confirmed successful incorporation of the drug into the interlayer
      spaces of the LGdH in all cases. From a comparison of the guest anion sizes and
      interlayer spacings, the active ingredients are believed to adopt intertwined
      bilayer configurations between the LGdH layers. The materials prepared by
      coprecipitation in general have noticeably higher drug loadings than those
      produced by ion exchange or self-assembly, as a result of the incorporation of
      some neutral drug into the composites. The LGdH-drug intercalates are stable at
      neutral pH, but rapidly degrade in acidic conditions to free Gd3+ into solution.
      While LGdH-nap releases its drug loading into solution very rapidly (within ca.
      1.5 h) at pH 7.4, LGdH-dic shows sustained release over 4 h, and LGdH-ibu extends
      this to 24 h. The latter composites therefore can be incorporated into enteric
      coated tablets to provide sustained release in the small intestine. The drug
      intercalates are highly biocompatible and retain the proton relaxivity properties
      of the parent LGdH-Cl, with the materials most promising for use as negative
      contrast agents in MRI. Overall, the LGdH-drug intercalation compounds appear to
      have great potential for use in theranostic applications.

PMID- 29355262
TI  - The antibacterial activity of polyoxometalates: structures, antibiotic effects
      and future perspectives.
AB  - Polyoxometalates (POMs) are, mostly anionic, metal oxide compounds that span a
      wide range of tunable physical and chemical features rendering them very
      interesting for biological purposes, an continuously emerging but little explored
      field. Due to their biological and biochemical effects, including antitumor, 
      viral and -bacterial properties, POMs and POM-based systems are considered as
      promising future metallodrugs. In this article, we focus on the antibacterial
      activity of POMs and their therapeutic potential in the battle against bacteria
      and their increasing resistance against pharmaceuticals. Recent advances in the
      synthesis of POMs are highlighted, with emphasis on the development and
      properties of biologically active POM-based hybrid and nanocomposite structures.
      By analysing the antibacterial activity and structure of POMs, putative mode of
      actions are provided, including potential targets for POM-protein interactions,
      and a structure-activity-relationship was established for a series of POMs
      against two bacteria, namely Helicobacter pylori and Streptococcus pneumoniae.

PMID- 29355264
TI  - First entry into nonmetal-centred porphycenes: synthesis of a phosphorus(v)
      complex of octaethylporphycene.
AB  - A phosphorus(v) complex of porphycene [P(OEPc)(OMe)2]PF6 (OEPc =
      2,3,6,7,12,13,16,17-octaethylporphycenato dianion) has been synthesized and
      structurally characterized as the first porphycene derivative incorporating
      nonmetal elements in the macrocyclic cavity. An extremely low energy level of the
      LUMO is observed, which is rationalized by the low-lying pi* orbital of the
      porphycene ring coupled with the insertion of the highly-inductive pentavalent
      phosphorus centre. The compound is luminescent in bright red with a quantum yield
      of 22.7% in CH2Cl2 at 298 K.

PMID- 29355265
TI  - Collection of amino acids and DNA from fingerprints using hydrogels.
AB  - The amino acid profile obtained from a fingerprint may provide valuable
      information on its donor. For forensic scientists, recovering evidence relating
      to the amino acid profile of a suspect can potentially be valuable for
      identification and exclusion purposes. Herein we detail the use of cross-linkable
      solutions of dextran-methacrylate to form hydrogels capable of collecting amino
      acids from surfaces followed by extraction and quantification with UPLC-MS. This
      method allows for the amino acid profile analysis of fingerprints while allowing
      for their increased visualisation at a later stage using the standard method of
      cyanoacrylation. We will demonstrate this method to also be capable of collecting
      DNA from fingerprints with a 20-60% yield in comparison to using a conventional
      cotton swab.

PMID- 29355266
TI  - Hydrogen bond-assisted homochiral lattice packing between inorganic helices built
      from heterometallic units.
AB  - Two enantiomorphic helical chains were constructed using heterometallic
      {TiMn2(MU3-O)} building units, and their final homochiral lattice packing was
      further transmitted by hydrogen bonding interactions between the chains with the
      same handedness.

PMID- 29355267
TI  - A fluorescent turn-on probe for cyanide anion detection based on an AIE active
      cobalt(ii) complex.
AB  - A new tetradentate polypyridine ligand that displays aggregation induced emission
      (AIE) characteristics has been synthesized. A coordination complex with CoCl2 has
      been prepared and characterized by X-ray crystallography. The Co(ii) complex
      retains the AIE activity of the ligand in aqueous solution while also exhibiting
      a selective turn-on fluorescence response in the presence of cyanide anion. A
      complex : CN- binding stoichiometry of 1 : 2 was indicated via Job plot analysis
      and the limit of detection for CN- was determined to be 0.59 MUM. The
      fluorescence response is attributed to coordination of CN- by the AIE active
      Co(ii) complex, resulting in decreased solubility in aqueous medium and
      concomitant generation of larger nanoaggregates as revealed by dynamic light
      scattering (DLS) measurements. The sensitivity and selectivity displayed by this
      sensor for CN- over other anions renders it a candidate probe for CN- detection
      in aqueous environments.

PMID- 29355268
TI  - Remarkable increase in the rate of the catalytic epoxidation of electron
      deficient styrenes through the addition of Sc(OTf)3 to the MnTMTACN catalyst.
AB  - The effect of Lewis acids on the catalytic activity of [Mn2(MU
      O)3(TMTACN)2](PF6)2 in the epoxidation of styrenes using hydrogen peroxide as the
      oxidant has shown that the addition of Sc(OTf)3 at low catalytic loading results
      in a very significant increase in the efficiency of the catalyst and a reduction
      of the reaction time to only 3 minutes in most cases.

PMID- 29355269
TI  - Correction: A pH responsive AIE probe for enzyme assays.
AB  - Correction for 'A pH responsive AIE probe for enzyme assays' by Leilei Shi et
      al., Analyst, 2018, DOI: 10.1039/c7an01710c.

PMID- 29355274
TI  - Adaptation of Rhodopseudomonas acidophila strain 7050 to growth at different
      light intensities: what are the benefits to changing the type of LH2?
AB  - Typical purple bacterial photosynthetic units consist of light harvesting
      one/reaction centre 'core' complexes surrounded by light harvesting two
      complexes. Factors such as the number and size of photosynthetic units per cell,
      as well as the type of light harvesting two complex that is produced, are
      controlled by environmental factors. In this paper, the change in the type of LH2
      present in the Rhodopsuedomonas acidophila strain 7050 is described when cells
      are grown at a range of different light intensities. This species contains
      multiple pucBA genes that encode the apoproteins that form light-harvesting
      complex two, and a more complex mixture of spectroscopic forms of this complex
      has been found than was previously thought to be the case. Femto-second time
      resolved absorption has been used to investigate how the energy transfer
      properties in the membranes of high-light and low-light adapted cells change as
      the composition of the LH2 complexes varies.

PMID- 29355275
TI  - Effects of volatile oil from ginger on the murine B16 melanoma cells and its
      mechanism.
AB  - In this study, the inhibitory effects of volatile oil from ginger on
      melanogenesis and its antioxidant characteristics were investigated. The effects
      of volatile oil from ginger on cell proliferation, melanin content and tyrosinase
      activity were determined using a microplate reader. In addition, the expression
      of melanogenesis-related protein was determined by western blotting. The results
      indicate that the tested concentrates of volatile oil from ginger showed
      inhibitory effects on cell proliferation and melanogenesis. This revealed that
      volatile oil from ginger exhibited apparent capacities for scavenging ROS and
      lipid peroxidation. Furthermore, volatile oil from ginger improved the activities
      of GSH, SOD and CAT in B16 melanoma cells. These results demonstrated that
      volatile oil from ginger suppressed melanin synthesis through its antioxidant
      properties and the inhibitory effects on tyrosinase activity and melanogensis
      related proteins. Hence, volatile oil from ginger could be used as an effective
      skin-whitening agent applied in food industry.

PMID- 29355276
TI  - 3D printed high density, reversible, chip-to-chip microfluidic interconnects.
AB  - Our latest developments in miniaturizing 3D printed microfluidics [Gong et al.,
      Lab Chip, 2016, 16, 2450; Gong et al., Lab Chip, 2017, 17, 2899] offer the
      opportunity to fabricate highly integrated chips that measure only a few mm on a
      side. For such small chips, an interconnection method is needed to provide the
      necessary world-to-chip reagent and pneumatic connections. In this paper, we
      introduce simple integrated microgaskets (SIMs) and controlled-compression
      integrated microgaskets (CCIMs) to connect a small device chip to a larger
      interface chip that implements world-to-chip connections. SIMs or CCIMs are
      directly 3D printed as part of the device chip, and therefore no additional
      materials or components are required to make the connection to the larger 3D
      printed interface chip. We demonstrate 121 chip-to-chip interconnections in an 11
      * 11 array for both SIMs and CCIMs with an areal density of 53 interconnections
      per mm2 and show that they withstand fluid pressures of 50 psi. We further
      demonstrate their reusability by testing the devices 100 times without seal
      failure. Scaling experiments show that 20 * 20 interconnection arrays are
      feasible and that the CCIM areal density can be increased to 88 interconnections
      per mm2. We then show the utility of spatially distributed discrete CCIMs by
      using an interconnection chip with 28 chip-to-world interconnects to test 45 3D
      printed valves in a 9 * 5 array. Each valve is only 300 MUm in diameter (the
      smallest yet reported for 3D printed valves). Every row of 5 valves is tested to
      at least 10 000 actuations, with one row tested to 1 000 000 actuations. In all
      cases, there is no sign of valve failure, and the CCIM interconnections prove an
      effective means of using a single interface chip to test a series of valve array
      chips.

PMID- 29355277
TI  - Probiotic/prebiotic correction for adverse effects of iron fortification on
      intestinal resistance to Salmonella infection in weaning mice.
AB  - Iron fortification has been associated with a modest increase in diarrhea risk
      among children. Herein, we investigate the correction for this unwanted side
      effect with probiotic/prebiotic supplementation in weaning mice. Iron
      fortification with 250 ppm and 500 ppm ferrous sulfate for 30 days significantly
      increased the species richness of the mouse gut microbiota compared to controls.
      The 500 ppm-FeSO4 diet caused a significantly decreased abundance of potentially
      beneficial Lactobacillus. During infection with the foodborne pathogen Salmonella
      enterica serovar Typhimurium (S. Typhimurium), mice on the 500 ppm-FeSO4 diet
      showed earlier appearance of poisoning symptoms, higher rates of weight and
      appetite loss, and lower survival rates, all of which were effectively reversed
      by supplementation with a probiotic (Lactobacillus acidophilus) or a prebiotic
      (inulin) for 7 days before infection. Iron fortification with 500 ppm ferrous
      sulfate also increased fecal shedding and spleen and liver load of viable S.
      Typhimurium, suggesting its promoting effect on pathogen colonization and
      translocation, and this negative effect was found to be well corrected by
      supplementation with Lactobacillus acidophilus or inulin. Light and transmission
      electron microscopic observation on the ileal villus structure revealed the
      histopathological impairment of the intestine by iron fortification with both 250
      ppm and 500 ppm ferrous sulfate, and the intestinal lesions were markedly
      alleviated by supplementation with Lactobacillus acidophilus or inulin. These
      results provide experimental evidence for the increased diarrhea risk upon iron
      fortification with high pathogen load, and demonstrate that probiotic or
      prebiotic supplementation can be used to eliminate the potential harm of iron
      fortification on gut health.

PMID- 29355278
TI  - A metagenomics approach to the intestinal microbiome structure and function in
      high fat diet-induced obesity mice fed with oolong tea polyphenols.
AB  - To investigate the modulatory effect of oolong tea polyphenols (OTP) on
      intestinal microbiota, OTP was prepared by column chromatography and its
      influence on the gut flora structure was analyzed by high-throughput sequencing
      with a human flora-associated high fat diet (HFD) induced obesity mouse model. We
      observed a robust increase in bacterial biodiversity and the abundance of genera
      known to be butyrate- and acetate-producing bacteria. A large increase in
      Bacteroidetes with a decrease in Firmicutes was observed after the administration
      of OTP for 4 weeks, and the corresponding decrease in the
      Firmicutes/Bacteroidetes ratio reflected the positive modulatory effect of OTP on
      the intestinal microbiota. In addition, KEGG pathways for the biosynthesis of
      amino acids, carbon metabolism, and the ribosome were among the most
      differentially expressed genes after OTP intervention. The current study revealed
      that OTP rich in tea catechins, especially O-methylated derivatives, may have
      prebiotic-like activity and can be used as a functional food component with
      potential therapeutic utility to prevent obesity-related metabolic disorders by
      manipulating the intestinal microbiota.

PMID- 29355280
TI  - Effect of geometrical parameters on rebound of impacting droplets on leaky
      superhydrophobic meshes.
AB  - When a droplet impacts a superhydrophobic sieve, a part of the droplet penetrates
      through it when the dynamic pressure (rhoU2) of the impinging droplet exceeds the
      breakthrough pressure (gammaGamma/A). At higher impact velocities, the ejected
      jet breaks and separates from the main droplet. The remaining part of the droplet
      bounces off the surface showing different modes (normal bouncing as a vertically
      elongated drop or pancake bouncing). In this work, we have studied the effect of
      different geometrical parameters of superhydrophobic copper meshes on different
      modes of droplet rebound. We observe three different effects in our study.
      Firstly, we observe pancake like bouncing, which is attributed to the capillary
      energy of the rebounding interface formed after the breaking of the ejected-jet.
      Secondly, we observe leakage of the droplet volume and kinetic energy due to the
      breaking of the ejected-jet, which leads to reduction in the contact times.
      Finally, we observe that for flexible meshes, the transition to pancake type
      bouncing is induced at lower Weber numbers. Flexibility also leads to a reduction
      in the volume loss from the ejected-jet. This study will be helpful in the design
      of superhydrophobic meshes for use under impact scenarios.

PMID- 29355281
TI  - The End of Acquired Immunodeficiency Syndrome (AIDS) in Singapore - Are We There
      Yet?

PMID- 29355282
TI  - Malignant Hyperthermia and Ryanodine Receptor Type 1 Gene (RyR1) Mutation in a
      Family in Singapore.
AB  - INTRODUCTION: Sporadic clinical episodes of malignant hyperthermia (MH) that
      develop during general anaesthesia (GA) have been reported in Singapore. However,
      there is no published local report of a confirmed case of MH susceptibility (MHS)
      by skeletal muscle contracture tests and/or molecular tests. MATERIALS AND
      METHODS: We report 2 patients from an extended family who developed signs of
      clinical MH while under GA. The MH episodes were successfully treated with
      intravenous dantrolene sodium. Sequence analysis of the entire Ryanodine Receptor
      Type 1 (RyR1) coding gene was carried out in an index patient. RESULTS: The index
      patient was found to carry a c.7373G>A (p.Arg2458His) mutation in exon 46. This
      particular mutation satisfies the criteria for a MHS causative mutation. Hence,
      the index patient was considered to be MHS and did not need to undergo further
      muscle contracture testing. The same mutation was also found in 3 other members
      of his extended family. CONCLUSION: This is the first report of a Singaporean
      family with at least 4 members carrying a MH-causative mutation in RyR1 gene.
      This report serves to highlight the existence of the putative gene for MH in
      Singapore, and the need for clinical vigilance during anaesthesia involving the
      use of triggering agents.

PMID- 29355283
TI  - Reliability and Validity of the English-, Chinese- and Malay-Language Versions of
      the World Health Organization Quality of Life (WHOQOL-BREF) Questionnaire in
      Singapore.
AB  - INTRODUCTION: The World Health Organization Quality of Life (WHOQOL-BREF)
      questionnaire is a 26-item questionnaire that evaluates 4 domains of quality of
      life (QoL), namely Physical, Psychological, Social Relationships and Environment.
      This study aimed to evaluate the validity and reliability of the WHOQOL-BREF
      among Singapore residents aged 21 and above. MATERIALS AND METHODS: We recruited
      participants from the general population by using multistage cluster sampling and
      participants from 2 hospitals by using convenience sampling. Participants
      completed either English, Chinese or Malay versions of the WHOQOL-BREF and the
      EuroQoL 5 Dimension 5 Levels (EQ-5D-5L) questionnaires. Confirmatory factor
      analysis, known-group validity, internal consistency (Cronbach's alpha) and test
      retest reliability using the intraclass correlation coefficient (ICC) were
      performed. RESULTS: Data from 1316 participants were analysed (Chinese: 46.9%,
      Malay: 41.0% and Indian: 11.7%; 57.5% mean, mean standard deviation [SD, range]
      age: 51.9 [15.68, 24 to 90] years); 154 participants took part in the retest in
      various languages (English: 60, Chinese: 49 and Malay: 45). Tucker-Lewis Index
      (TLI) was 0.919, 0.913 and 0.909 for the English, Chinese and Malay versions,
      respectively. Cronbach's alpha exceeded 0.7 and ICC exceeded 0.4 for all domains
      in all language versions. CONCLUSION: The WHOQOL-BREF is valid and reliable for
      assessing QoL in Singapore. Model fit is reasonable with room for improvement.

PMID- 29355284
TI  - Unusual Clinical Presentation of Nutcracker Phenomenon.

PMID- 29355285
TI  - Subpleural Lung Cysts in Children with Trisomy 21.

PMID- 29355286
TI  - An Audit of Critical Value Parameters at Two Regional Hospitals in Singapore.

PMID- 29355287
TI  - Auto-Amputations.

PMID- 29355290
TI  - Ergonomic interventions and prevention - a need for better understanding of
      implementation.

PMID- 29355291
TI  - Objectively measured physical activity of hospital shift workers.
AB  - Objectives Shift work may alter workers' leisure-time and occupational physical
      activity (PA) levels, which might be one of the potential underlying mechanisms
      of the negative health effects of shift work. Therefore, we compared objectively
      measured PA levels between hospital shift and non-shift workers. Methods Data
      were used from Klokwerk+, a cohort study examining the health effects of shift
      work among healthcare workers employed in hospitals. In total, 401 shift workers
      and 78 non-shift workers were included, all of whom wore Actigraph GT3X
      accelerometers for up to seven days. Time spent sedentary, standing, walking,
      running, stairclimbing, and cycling during leisure time and at work was estimated
      using Acti4 software. Linear regression was used to compare proportions of time
      spent in these activities between hospital shift and non-shift workers. Results
      Average accelerometer wear-time was 105.9 [standard deviation (SD) 14.0] waking
      hours over an average of 6.9 (SD 0.6) days. No differences between hospital shift
      and non-shift workers were found in leisure-time PA (P>0.05). At work, shift
      workers were less sedentary [B=-10.6% (95% CI -14.3- -6.8)] and spent larger
      proportions of time standing [B=9.5% (95% CI 6.4-12.6)] and walking [B=1.2% (95%
      CI 0.1-2.2)] than non-shift workers. However, these differences in occupational
      PA became smaller when the number of night shifts during accelerometer wear-time
      increased. Conclusions Leisure-time PA levels of hospital shift workers were
      similar to those of non-shift workers, but shift workers were less sedentary and
      more physically active (ie, standing/walking) at work. Future research to the
      role of occupational activities in the health effects of shift work is
      recommended.

PMID- 29355292
TI  - Effectiveness of ultrasound-guided vs direct approach corticosteroid injections
      for carpal tunnel syndrome: A double-blind randomized controlled trial.
AB  - OBJECTIVE: To compare the outcomes of ultrasound-guided vs direct approach
      corticosteroid injection in patients with idiopathic carpal tunnel syndrome.
      METHODS: A double-blind randomized controlled study. Wrists affected by carpal
      tunnel syndrome were randomized to the ultrasound-guided (n = 22 wrists) or
      direct approach injection group (n = 17 wrists) before receiving 1 ml
      Betamethasone. Outcome measures were physical findings and electrodiagnostic
      parameters assessed at 1, 3 and 6 months after injection. Complications were also
      recorded. RESULTS: Both groups showed improvement through-out the follow-up
      period after injections, in physical findings and in most electrodiagnostic
      parameters (all p<0.05). The ultrasound-guided injection group showed greater
      improvements in the Semmes-Weinstein Monofilament test result (p = 0.004),
      sensory nerve conduction velocity (p = 0.038), and digit-4 comparison study
      result (p = 0.046). Three wrists with weakness were found in the direct approach
      injection group, yet none were noted in the ultrasound-guided injection group
      (p=0.040). CONCLUSION: Both ultrasound-guided and direct approach corticosteroid
      injection protocols improved clinical symptoms and signs, physical function, and
      most electrodiagnostic parameters of patients with carpal tunnel syndrome
      throughout the follow-up period. However, the ultrasound-guided injection group
      showed greater improvements in the Semmes-Weinstein Monofilament test, sensory
      nerve conduction velocity, and digit-4 comparison study.

PMID- 29355293
TI  - Bladder irrigation with Chlorhexidine reduces bacteriuria in persons with spinal
      cord injury.
AB  - OBJECTIVE: To explore whether bladder irrigation with chlorhexidine: (i) can
      reduce bacteriuria, and (ii) is a practically feasible option in subjects with
      spinal cord injury practicing intermittent self-catheterization. DESIGN: A
      prospective, non-controlled, open, multi-centre study. METHODS: Fifty patients
      with spinal cord injury, practicing intermittent self-catheterization, with a
      history of recurrent urinary tract infections were screened for bacteriuria at
      follow-up visits to 4 spinal cord injury centres in Sweden. Twenty-three patients
      had a positive urine culture (> 105 CFU/ml of > 1 bacterial species), of which 19
      completed the study. Subjects proceeded with bladder irrigation, using 120 ml of
      0.2% chlorhexidine solution twice daily for up to 7 days. Urine samples were
      taken twice daily. Response to treatment was defined as reduction in bacterial
      counts to < 103 CFU/ml. RESULTS: Fourteen of 19 subjects reduced their bacterial
      counts to or below the set limit. Subsequent return of above-endpoint bacteriuria
      was seen in most of the subjects. However, there were significantly fewer
      subjects with bacteriuria after treatment (p <0.005). CONCLUSION: Bladder
      irrigation with chlorhexidine, using intermittent self-catheterization, reduced
      bacteriuria in the majority of subjects with spinal cord injury and bacteriuria.
      The addition of bladder irrigation was practically feasible in the short time
      frame of this study.

PMID- 29355294
TI  - Long noncoding RNAs in respiratory diseases.
AB  - Recently developed RNA microarrays and high-throughput sequencing techniques have
      demonstrated that long non-coding RNAs (lncRNAs) play important roles in a wide
      range of biological processes. Emerging evidence has confirmed the relevance of
      lncRNAs to diverse types of human disease, including cancer and cardiovascular
      disease. In this review, we discuss the important functions of lncRNAs in
      respiratory diseases. Because the reviewed studies have mainly focused on non
      small cell lung cancer, future work will need to extend the studies into other
      respiratory diseases. From a clinical perspective, targeting lncRNAs as a novel
      therapeutic strategy in respiratory diseases will require further study to
      further clarify their biological functions.

PMID- 29355295
TI  - Educational value of virtual reality for medical students: an interactive lecture
      on carotid stenting.

PMID- 29355296
TI  - Interventions for femoropopliteal disease: endo first, second and last?

PMID- 29355297
TI  - Total endovascular arch repair is the procedure of the future.
AB  - INTRODUCTION: This study evaluates the current experience on endovascular repair
      of the aortic arch pathologies, the feasibility and safety of the procedure.
      EVIDENCE ACQUISITION: A systematic review was performed. MEDLINE, CENTRAL, and
      Cochrane databases were searched with PRISMA methodology for published studies
      reporting on endovascular repair of aortic arch pathologies from 2000 to 2018.
      EVIDENCE SYNTHESIS: Thirteen non-randomized retrospective studies (either single
      or multicenter), two multicenter Registries and one multicenter non-randomized
      interventional study were included in the systematic review. The total number of
      patients who underwent total endovascular repair of the aortic arch pathology
      with either fenestrated, branched, or a combination of those devices or chimney
      technique was 952 patients (73%; 634/872 males, mean age ranging from 51 to 78
      years). The technical success rate was 96.7% (921/952), while the 30-day
      mortality rate was 3.3% (32/952). The most common adverse events were endoleak
      type I (13.5%; 35/259), stroke (5.1%; 49/952), spinal cord ischemia (1.4%;
      14/952) and retrograde dissection (1%; 8/952). During the follow-up period (mean
      ranging: 16.9 to 41.4 months; median ranging: 9 to 44.8 months) the total number
      of deaths was 31 (4.4%; 31/693). The total loss of supra-aortic vessel patency
      rate was 1.7% (14/803) and a re-intervention was needed in 50 patients (9%;
      50/559; 11 open conversion). CONCLUSIONS: Endovascular repair of aortic arch
      pathologies is a feasible treatment option with good early and reasonable mid
      term outcomes. This treatment modality approaches a level of maturity and may be
      considered as a solid alternative method of treatment.

PMID- 29355298
TI  - Substrate-Independent Epitaxial Growth of the Metal-Organic Framework MOF-508a.
AB  - Plasmachemical deposition is a substrate-independent method for the conformal
      surface functionalization of solid substrates. Structurally well-defined pulsed
      plasma deposited poly(1-allylimidazole) layers provide surface imidazole linker
      groups for the directed liquid-phase epitaxial (layer-by-layer) growth of metal
      organic frameworks (MOFs) at room temperature. For the case of microporous [Zn
      (benzene-1,4-dicarboxylate)-(4,4'-bipyridine)0.5] (MOF-508), the MOF-508a
      polymorph containing two interpenetrating crystal lattice frameworks undergoes
      orientated Volmer-Weber growth and displays CO2 gas capture behavior at
      atmospheric concentrations in proportion to the number of epitaxially grown MOF
      508 layers.

PMID- 29355299
TI  - Enhancing the Performance of CdSe/CdS Dot-in-Rod Light-Emitting Diodes via
      Surface Ligand Modification.
AB  - The surface ligands on colloidal nanocrystals (NCs) play an important role in the
      performance of NC-based optoelectronic devices such as photovoltaic cells,
      photodetectors, and light-emitting diodes (LEDs). On one hand, the NC emission
      depends critically on the passivation of the surface to minimize trap states that
      can provide nonradiative recombination channels. On the other hand, the
      electrical properties of NC films are dominated by the ligands that constitute
      the barriers for charge transport from one NC to its neighbor. Therefore, surface
      modifications via ligand exchange have been employed to improve the conductance
      of NC films. However, in LEDs, such surface modifications are more critical
      because of their possible detrimental effects on the emission properties. In this
      work, we study the role of surface ligand modifications on the optical and
      electrical properties of CdSe/CdS dot-in-rods (DiRs) in films and investigate
      their performance in all-solution-processed LEDs. The DiR films maintain high
      photoluminescence quantum yield, around 40-50%, and their electroluminescence in
      the LED preserves the excellent color purity of the photoluminescence. In the
      LEDs, the ligand exchange boosted the luminance, reaching a fourfold increase
      from 2200 cd/m2 for native surfactants to 8500 cd/m2 for the exchanged
      aminoethanethiol (AET) ligands. Moreover, the efficiency roll-off, operational
      stability, and shelf life are significantly improved, and the external quantum
      efficiency is modestly increased from 5.1 to 5.4%. We relate these improvements
      to the increased conductivity of the emissive layer and to the better charge
      balance of the electrically injected carriers. In this respect, we performed
      ultraviolet photoelectron spectroscopy (UPS) to obtain a deeper insight into the
      band alignment of the LED structure. The UPS data confirm similar flat-band
      offsets of the emitting layer to the electron- and hole-transport layers in the
      case of AET ligands, which translates to more symmetric barriers for charge
      injection of electrons and holes. Furthermore, the change in solubility of the
      NCs induced by the ligand exchange allows for a layer-by-layer deposition process
      of the DiR films, which yields excellent homogeneity and good thickness control
      and enables the fabrication of all the LED layers (except for cathode and anode)
      by spin-coating.

PMID- 29355300
TI  - Enhanced Piezoelectricity in a Robust and Harmonious Multilayer Assembly of
      Electrospun Nanofiber Mats and Microbead-Based Electrodes.
AB  - Here, we present a simple yet highly efficient method to enhance the output
      performance of a piezoelectric device containing electrospun nanofiber mats.
      Multiple nanofiber mats were assembled together to harness larger piezoelectric
      sources in the as-spun fibers, thereby providing enhanced voltage and current
      outputs compared to those of a single-mat device. In addition to the multilayer
      assembly, microbead-based electrodes were integrated with the nanofiber mats to
      deliver a complexed compression and tension force excitation to the piezoelectric
      layers. A vacuum-packing process was performed to attain a tight and well
      organized assembly of the device components even though the total thickness was
      several millimeters. The integrated piezoelectric device exhibited a maximum
      voltage and current of 10.4 V and 2.3 MUA, respectively. Furthermore, the robust
      integrity of the device components could provide high-precision sensitivity to
      perceive small pressures down to approximately 100 Pa while retaining a linear
      input-output relationship.

PMID- 29355302
TI  - Gate-Tunable WSe2/SnSe2 Backward Diode with Ultrahigh-Reverse Rectification
      Ratio.
AB  - Backward diodes conduct more efficiently in the reverse bias than in the forward
      bias, providing superior high-frequency response, temperature stability,
      radiation hardness, and 1/f noise performance than a conventional diode
      conducting in the forward direction. Here, we demonstrate a van der Waals
      material-based backward diode by exploiting the giant staggered band offsets of
      WSe2/SnSe2 vertical heterojunction. The diode exhibits an ultrahigh-reverse
      rectification ratio (R) of ~2.1 * 104, and the same is maintained up to an
      unusually large bias of 1.5 V-outperforming existing backward diode reports using
      conventional bulk semiconductors as well as one- and two-dimensional materials by
      more than an order of magnitude while maintaining an impressive curvature
      coefficient (gamma) of ~37 V-1. The transport mechanism in the diode is shown to
      be efficiently tunable by external gate and drain bias, as well as by the
      thickness of the WSe2 layer and the type of metal contacts used. These results
      pave the way for practical electronic circuit applications using two-dimensional
      materials and their heterojunctions.

PMID- 29355301
TI  - Extraordinary Interfacial Stitching between Single All-Inorganic Perovskite
      Nanocrystals.
AB  - All-inorganic cesium lead halide perovskite nanocrystals are extensively studied
      because of their outstanding optoelectronic properties. Being of a cubic shape
      and typically featuring a narrow size distribution, CsPbX3 (X = Cl, Br, and I)
      nanocrystals are the ideal starting material for the development of homogeneous
      thin films as required for photovoltaic and optoelectronic applications. Recent
      experiments reveal spontaneous merging of drop-casted CsPbBr3 nanocrystals, which
      is promoted by humidity and mild-temperature treatments and arrested by electron
      beam irradiation. Here, we make use of atom-resolved annular dark-field imaging
      microscopy and valence electron energy loss spectroscopy in a state-of-the-art
      low-voltage monochromatic scanning transmission electron microscope to
      investigate the aggregation between individual nanocrystals at the atomic level.
      We show that the merging process preserves the elemental composition and
      electronic structure of CsPbBr3 and takes place between nanocrystals of different
      sizes and orientations. In particular, we reveal seamless stitching for aligned
      nanocrystals, similar to that reported in the past for graphene flakes. Because
      the crystallographic alignment occurs naturally in drop-casted layers of CsPbX3
      nanocrystals, our findings constitute the essential first step toward the
      development of large-area nanosheets with band gap energies predesigned by the
      nanocrystal choice-the gateway to large-scale photovoltaic applications of
      inorganic perovskites.

PMID- 29355303
TI  - Genuine Unilamellar Metal Oxide Nanosheets Confined in a Superlattice-like
      Structure for Superior Energy Storage.
AB  - Two-dimensional (2D) metal oxide nanosheets can exhibit exceptional
      electrochemical performance owing to their shortened ion diffusion distances,
      abundant active sites, and various valence states. Especially, genuine
      unilamellar nanosheets with an atomic-scale thickness are expected to exhibit the
      ultimate energy storage capability but have not yet achieved their potential.
      Here, we demonstrate the utilization of genuine unilamellar MnO2 nanosheets for
      high-performance Li and Na storage using an alternately stacked MnO2/graphene
      superlattice-like structure. Different from previous reports, all unilamellar
      MnO2 nanosheets are separated and stabilized between the graphene monolayers,
      resulting in highly reversible 2D-confined conversion processes. As a
      consequence, large specific capacities of 1325 and 795 mA h g-1 at 0.1 A g-1,
      high-rate capacities of 370 and 245 mA h g-1 at 12.8 A g-1, and excellent cycling
      stabilities after 5000 cycles with ~0.004% and 0.0078% capacity decay per cycle
      were obtained for Li and Na storage, respectively, presenting the best reported
      performance to date.

PMID- 29355304
TI  - Computationally Assessing the Bioactivation of Drugs by N-Dealkylation.
AB  - Cytochromes P450 (CYPs) oxidize alkylated amines commonly found in drugs and
      other biologically active molecules, cleaving them into an amine and an aldehyde.
      Metabolic studies usually neglect to report or investigate aldehydes, even though
      they can be toxic. It is assumed that they are efficiently detoxified into
      carboxylic acids and alcohols. Nevertheless, some aldehydes are reactive and
      escape detoxification pathways to cause adverse events by forming DNA and protein
      adducts. Herein, we modeled N-dealkylations that produce both amine and aldehyde
      metabolites and then predicted the reactivity of the aldehyde. This model used a
      deep learning approach previously developed by our group to predict other types
      of drug metabolism. In this study, we trained the model to predict N-dealkylation
      by human liver microsomes (HLM), finding that including isozyme-specific
      metabolism data alongside HLM data significantly improved results. The final HLM
      model accurately predicted the site of N-dealkylation within metabolized
      substrates (97% top-two and 94% area under the ROC curve). Next, we combined the
      metabolism, metabolite structure prediction, and previously published reactivity
      models into a bioactivation model. This combined model predicted the structure of
      the most likely reactive metabolite of a small validation set of drug-like
      molecules known to be bioactivated by N-dealkylation. Applying this model to
      approved and withdrawn medicines, we found that aldehyde metabolites produced
      from N-dealkylation may explain the hepatotoxicity of several drugs: indinavir,
      piperacillin, verapamil, and ziprasidone. Our results suggest that N-dealkylation
      may be an under-appreciated bioactivation pathway, especially in clinical
      contexts where aldehyde detoxification pathways are inhibited. Moreover, this is
      the first report of a bioactivation model constructed by combining a metabolism
      and reactivity model. These results raise hope that more comprehensive models of
      bioactivation are possible. The model developed in this study is available at
      http://swami.wustl.edu/xenosite/ .

PMID- 29355305
TI  - Superrepression through Altered Corepressor-Activated Protein:Protein
      Interactions.
AB  - Small molecules regulate transcription in both eukaryotes and prokaryotes by
      either enhancing or repressing assembly of transcription regulatory complexes.
      For allosteric transcription repressors, superrepressor mutants can exhibit
      increased sensitivity to small molecule corepressors. However, because many
      transcription regulatory complexes assemble in multiple steps, the superrepressor
      phenotype can reflect changes in any or all of the individual assembly steps.
      Escherichia coli biotin operon repression complex assembly, which responds to
      input biotin concentration, occurs via three coupled equilibria, including
      corepressor binding, holorepressor dimerization, and binding of the dimer to DNA.
      A genetic screen has yielded superrepressor mutants that repress biotin operon
      transcription in vivo at biotin concentrations much lower than those required by
      the wild type repressor. In this work, isothermal titration calorimetry and
      sedimentation measurements were used to determine the superrepressor biotin
      binding and homodimerization properties. The results indicate that, although all
      variants exhibit biotin binding affinities similar to that measured for BirAwt,
      five of the six superrepressors show altered homodimerization energetics.
      Molecular dynamics simulations suggest that the altered dimerization results from
      perturbation of an electrostatic network that contributes to allosteric
      activation of BirA for dimerization. Modeling of the multistep repression complex
      assembly for these proteins reveals that the altered sensitivity of the
      transcription response to biotin concentration is readily explained solely by the
      altered superrepressor homodimerization energetics. These results highlight how
      coupled equilibria enable alterations in a transcription regulatory response to
      input signal through an indirect mechanism.

PMID- 29355306
TI  - Cu3Mo2O9 Nanosheet Array as a High-Efficiency Oxygen Evolution Electrode in
      Alkaline Solution.
AB  - Developing highly active and sustained oxygen evolution reaction (OER) catalysts
      for energy-saving electrolytic hydrogen generation is highly attractive. In this
      work, we report the development of a Cu3Mo2O9 nanosheet array on nickel foam
      (Cu3Mo2O9/NF) as a highly active OER catalyst. Such Cu3Mo2O9/NF shows high
      catalytic activity in 1.0 M KOH, passing 50 mA cm-2 at an overpotential of 325
      mV. It also shows superior long-term durability more than 24 h with a turnover
      frequency (TOF) of 0.09 mol O2 s-1 at overpotential of 400 mV.

PMID- 29355308
TI  - High-Temperature, High-Pressure Hydrothermal Synthesis, Crystal Structure,
      Thermal Stability, and Solid State NMR Spectroscopy of an Aluminum Borate,
      Ba[AlB4O8(OH)].
AB  - A new aluminum borate, Ba[AlB4O8(OH)], has been synthesized under high
      temperature, high-pressure hydrothermal conditions at 550  degrees C and 1400 bar
      and its structure characterized by single-crystal X-ray diffraction, IR, and MAS
      11B, and 27Al NMR spectroscopy. It crystallizes in the monoclinic space group
      P21/n with a = 7.0695(5) A, b = 15.108(1) A, c = 7.0746(5) A, beta = 93.593(2)
      degrees , and Z = 4. Its 2D layer structure is formed of corner-sharing B4O8(OH)
      clusters and AlO4 tetrahedra with the charge-compensating Ba2+ cations between
      the layers. While the same in the framework composition, the title compound and
      the hydrate, Ba[AlB4O8(OH)].H2O, differ greatly in structure. Although the title
      compound contains an OH group, it is thermally stable up to 740  degrees C and
      then decomposes into Ba2Al2B8O17, as indicated by high-temperature DSC/TG
      analysis and powder X-ray diffraction.

PMID- 29355307
TI  - Fluorescent Hydrogel Generated Conveniently from a Perylene Tetracarboxylate
      Derivative of Titanium(IV) Alkoxide.
AB  - Organic gelators and metal-coordination frameworks based on perylene derivatives
      as functional materials have attracted great attention because of their intense
      fluorescence emission as well as unique electronic and photonic properties. We
      report here the structures and properties of a luminescent titanium(IV)
      coordination compound of a perylene tetracarboxylate (PTC) derivative,
      [Ti2(OiPr)6(L1)(phen)2] (1), along with its two naphthalene analogues,
      [Ti2(OiPr)6(L2)(phen)2] (2) and [Ti2(OiPr)6(L2)(bpy)2] (3), where L1 = 3,9
      dicarboxylate-(4,10-diisopropanolcarboxylate)perylene, phen = 1,10
      phenanthroline, L2 = 1,5-dicarboxylate-(2,6-diisopropanolcarboxylate)naphthalene,
      and bpy = 2,2'-bipyridine. Compound 1 is a rare early-transition-metal PTC
      coordination compound that can be simply prepared in one pot as crystals by a low
      heat synthesis. Unlike those of paramagnetic late-transition-metal PTC compounds,
      compound 1 showed intense fluorescence emission. More remarkably, the crystals of
      1 can be turned immediately to a fluorescent hydrogel just through a simple
      procedure, putting the crystals in water and then treating with ultrasound. No
      acid catalyst or pH adjustment is needed. Hydrolysis of the titanium isopropanol
      group in water and pi-pi interaction of the perylene and phen play important
      roles in the gelation process. The film prepared from the gel can be used as a
      visual fluorescence sensor for aromatic amines and phenols, which are hazards for
      the human and environment.

PMID- 29355309
TI  - Zero-Order Release of Gossypol Improves Its Antifertility Effect and Reduces Its
      Side Effects Simultaneously.
AB  - Gossypol was considered a promising male contraceptive but finally failed due to
      two side effects: hypokalemia and the irreversibility of its contraceptive
      effect. Here we demonstrate that sustained zero-order release could be a solution
      for these problems. The in vitro release of gossypol from gossypol/PEG layer-by
      layer films follows a perfect zero-order kinetics. In vivo tests indicate that
      the films can maintain the plasma drug concentration constant in male SD rats for
      ~20 days for a 30-bilayer film. The plasma drug concentration is 2 orders of
      magnitude lower than the peak plasma drug concentration when administered orally
      and the daily dose is >50-fold lower than the commonly used contraceptive oral
      dose. However, significant antifertility effects were still observed.
      Furthermore, hypokalemia was not observed, and the antifertility effects can be
      reversed after a recovery period. The results suggest that zero-order release can
      significantly improve the desired antifertility effect of gossypol and,
      meanwhile, significantly reduce its side effects. We envision the drug could be
      developed to be an effective, safe, and reversible male contraceptive by zero
      order release.

PMID- 29355310
TI  - Exploration of Hypervalent Lewis Acid/Base Interactions in 2-(2'-Thiazolyl)-3
      thienylphosphanes.
AB  - The synthesis of a series of conjugated organophosphorus materials with
      intramolecular Lewis acid/base interactions and the exploration of the electronic
      nature of the bonding around the resulting hypervalent phosphorus centers are
      reported. To further establish the influence of increasing the size of the pi
      conjugated backbone, two scaffolds, thiazolyl-thiophene and benzothiazolyl
      thiophene, were included in this study. Single-crystal X-ray crystallography of
      several of the compounds supports the hypervalent nature of the phosphorus center
      in the new species. Surprisingly, altering the Lewis acidity of the phosphorus
      center via oxidation or methylation impacts the coordinating mode of the
      thiazolyl substituent, which also has considerable impact on the photophysical
      and electrochemical properties of the pi-conjugated molecular scaffolds. Through
      theoretical calculations involving natural bond orbital (NBO) analysis and atom
      in-molecules (AIM) correlation, the existence and electronic nature of weak
      hypervalent bonding interactions around the phosphorus center was solidified as
      weak 3c-4e and/or sigma-hole bonds, depending on the coordination mode of the
      peripheral thiazolyl substituent as well as the Lewis acidity of the phosphorus
      center.

PMID- 29355311
TI  - Unexpected Behavior of Np in Oxo-selenate/Oxo-selenite Systems.
AB  - A study of neptunium (Np) chemistry in the complex oxo-selenium system has been
      performed. Hereby, two sets of precipitation experiments were conducted,
      investigating the influence of the initial oxidation state of selenium using
      SeIVO2 and H2SeVIO4 with NpV in alkali nitrate solution, keeping the ratio of
      Np/Se constant. Surprising results were observed. Five novel neptunium and
      selenium bearing compounds have been obtained by slow evaporation from aqueous
      solution. The novel NpIV phase K4-x[Np(SeO3)4-x(HSeO3)x].(H2O)1.5 (1)
      crystallizes in green-colored, plate-shaped crystals and was obtained by adding
      SeO2 and ANO3 to a NpV stock solution. Single-crystal X-ray diffraction reveals
      one-dimensional chain structures composed of square antiprismatic NpO8 polyhedra
      linked via four trigonal pyramidal SeO3 and HSeO3 units. Raman spectral analysis
      supports the presence of both selenite and hydroselenite due to the presence of
      corresponding modes within the spectra. The addition of selenic acid to a NpV
      stock solution resulted in the precipitation of elongated rose prisms of
      K2[(NpO2)2(SeO4)3(H2O)2].(H2O)1.5 (2), Rb2[(NpO2)2(SeO4)3(H2O)2].(H2O)2 (3) and
      K9[(NpO2)9(SeO4)13.5(H2O)6].(H2O)12 (4) as well as light red plates of
      Cs2[(NpO2)2(SeO4)3] (5). To our knowledge, this is the first report of NpVI
      selenates. All four structures show two-dimensional layered structures with
      alkali cations acting as charge balancing counter cations. Hereby the layers of
      compounds 2 and 3 are found to be orientational geometric isomers. Distinctly
      different phenomena are made responsible for the phase formation within these
      systems. The kinetically driven process of NpV disproportionation led to the
      formation of the NpIV selenites in the SeIV-based system, whereas the oxidation
      of NpV by reduction of nitrate in acidic conditions is responsible for the
      formation of the NpVI selenates in the SeVI system. The influence of air oxygen
      is also discussed for the latter reaction.

PMID- 29355312
TI  - A Copper(II) Nitrite That Exhibits Change of Nitrite Binding Mode and Formation
      of Copper(II) Nitrosyl Prior to Nitric Oxide Evolution.
AB  - The proton-coupled reduction of CuII-bound nitrite (NO2-) to nitric oxide (NO2- +
      2H+ + e- -> NO(g) + H2O), such as occurs in the enzyme copper nitrite reductase,
      is investigated in this work. Our studies focus on the copper(II/I) model
      complexes [(L2)Cu(H2O)Cl] (1), [(L2)Cu(ONO)] (2), [(L2)Cu(CH3CO2)] (3), and
      [Co(Cp)2][(L2)Cu(NO2)(CH3CN] (4), where HL2 = N-[2-(methylthio)ethyl]-2'
      pyridinecarboxamide. Complex 1 readily reacts with a NO2- anion to form the
      nitrito-O-bound copper(II) complex 2. Electrochemical reduction of CuII -> CuI
      indicates coordination isomerization from asymmetric nitrito-kappa2-O,O to nitro
      kappa1-N. Isolation and spectroscopic characterization of 4 support this notion
      of nitrite coordination isomerization (nuCu-N ~ 460 cm-1). A reduction of 2,
      followed by reaction with acetic acid, causes evolution of stoichiometric NO via
      the transient copper(II) nitrosyl species and subsequent formation of the acetate
      bound complex 3. The probable copper nitrosyl intermediate [(L2)Cu(NO)(CH3CN)]+
      of the {CuNO}10 type is evident from low-temperature UV-vis absorption (lambdamax
      = 722 nm) and electron paramagnetic resonance spectroscopy. A density functional
      theory (DFT)-optimized model of [(L2)Cu(NO)(CH3CN)]+ shows end-on NO binding to
      Cu with Cu-N(NO) and N-O distances of 1.989 and 1.140 A, respectively, and a Cu-N
      O angle of 119.25 degrees , consistent with the formulation of CuII-NO*. A spin
      state change that triggers NO release is observed. Considering singlet- and
      triplet-state electronic configurations of this model, DFT-calculated nuNO values
      of 1802 and 1904 cm-1, respectively, are obtained. We present here important
      mechanistic aspects of the copper-mediated nitrite reduction pathway with the use
      of model complexes employing the ligand HL2 and an analogous phenyl-based ligand,
      N-[2-(methylthio)phenyl]-2'-pyridinecarboxamide (HL1).

PMID- 29355313
TI  - Reversible Phase Transition with Ultralarge Dielectric Relaxation Behaviors in
      Succinimide Lithium(I) Hybrids.
AB  - Dielectric relaxations have widely applied on high permittivity capacitors,
      dielectric switches, ferroelectrics, pyroelectrics, and electrical insulating
      materials. However, few investigations of large dielectric relaxation behaviors
      on organic-inorganic hybrid materials have been documented before. Here we
      present a novel two-dimensional succinimide lithium(I) hybrid compound,
      [Li(PDD)2ClO4]n, 1, (PDD = 2,5-pyrrolidinedione = succinimide) which shows
      reversible phase transition behavior in the vicinity of 228 K accompanied by an
      unusual symmetry breaking from I41/amd to C2/c. X-ray single crystal diffractions
      analysis indicates the twist motion of pyrrolidine heterocycles, and order
      disorder motion of ClO4- anions triggered the reversible phase transition. By
      means of an intuitive crystallographic model (rattling ion model), we further
      illustrated the mechanism of the interesting reversible phase transition.
      Particularly, 1 shows ultralarge dielectric relaxation behavior in the vicinity
      of the phase transition by its dielectric constant dependence on temperatures and
      frequencies as well as its Cole-Cole relation.

PMID- 29355314
TI  - N-Heterocyclic Carbenes as a Robust Platform for Surface-Enhanced Raman
      Spectroscopy.
AB  - Surface-enhanced Raman spectroscopy (SERS) underpins a wide range of commercial
      and fundamental applications. SERS often relies on ligands, usually thiols, bound
      to a noble metal surface. The difficulty of straightforward thiol synthesis
      combined with their instability on surfaces highlights the need for alternative
      ligand design. We present the first example of SERS utilizing N-heterocyclic
      carbene ligands. A general three step synthesis is presented for functionalized
      NHC-CO2 adducts. These ligands are deposited on SERS-active gold film-over
      nanosphere substrates (AuFONs) in solvent-free and base-free conditions, which
      prevents fouling. The resulting films are found to be robust and capable of
      postsynthetic modifications.

PMID- 29355316
TI  - Rotaxanes as Mechanochromic Fluorescent Force Transducers in Polymers.
AB  - The integration of mechanophores, motifs that transduce mechanical forces into
      chemical reactions, allows creating materials with stress-dependent properties.
      Typical mechanophores are activated by cleaving weak covalent bonds, but these
      reactions can also be triggered by other stimuli, and this renders the behavior
      unspecific. Here we show that this problem can be overcome by extending the
      molecular-shuttle function of rotaxanes to mechanical activation. A mechanically
      interlocked mechanophore composed of a fluorophore-carrying macrocycle and a
      dumbbell-shaped molecule containing a matching quencher was integrated into a
      polyurethane elastomer. Deformation of this polymer causes a fluorescence turn
      on, due to the spatial separation of fluorophore and quencher. This process is
      specific, efficient, instantly reversible, and elicits an easily detectable
      optical signal that correlates with the applied force.

PMID- 29355317
TI  - Modular Synthesis of Dipyrroloquinolines: A Combined Synthetic and Mechanistic
      Study.
AB  - A straightforward synthesis of [1,2-a][3',2'-c]dipyrroloquinolines has been
      developed generating up to eight new sigma-bonds and five new stereogenic centers
      in a simple and modular one-pot operation. Generally good to excellent yields and
      moderate to good stereoselectivities in favor of the all-cis stereoisomer were
      observed. A detailed investigation combining synthetic studies, analytical
      measurements, and theoretical calculations has been conducted to elucidate the
      reaction mechanism using ESI- and liquid-beam IR-laser desorption mass
      spectrometry as well as DFT calculations. Key steps of this sequential
      transformation include a Lewis acid-catalyzed vinylogous Mukaiyama-Mannich
      reaction of bis(silyl) dienediolate 1 and a Bronsted acid-promoted Mannich-Pictet
      Spengler reaction cascade reaction to complete the synthesis of the
      dipyrroloquinoline core of the target compounds.

PMID- 29355315
TI  - Inhibition of Glucose Transport by Tomatoside A, a Tomato Seed Steroidal Saponin,
      through the Suppression of GLUT2 Expression in Caco-2 Cells.
AB  - We investigated whether tomatoside A (5alpha-furostane-3beta,22,26-triol-3-[O
      beta-d-glucopyranosyl (1->2)-beta-d-glucopyranosyl (1->4)-beta-d
      galactopyranoside] 26-O-beta-d-glucopyranoside), a tomato seed saponin, may play
      a role in the regulation of intestinal glucose transport in human intestinal Caco
      2 cells. Tomatoside A could not penetrate through Caco-2 cell monolayers, as
      observed in the transport experiments using liquid chromatography-mass
      spectrometry. The treatment of cells with 10 MUM tomatoside A for 3 h resulted in
      a 46.0% reduction in glucose transport as compared to untreated cells. Western
      blotting analyses revealed that tomatoside A significantly (p < 0.05) suppressed
      the expression of glucose transporter 2 (GLUT2) in Caco-2 cells, while no change
      in the expression of sodium-dependent glucose transporter 1 was observed. In
      glucose transport experiments, the reduced glucose transport by tomatoside A was
      ameliorated by a protein kinase C (PKC) inhibitor and a multidrug resistance
      associated protein 2 (MRP2) inhibitor. The tomatoside A-induced reduction in
      glucose transport was restored in cells treated with apical sodium-dependent bile
      acid transporter (ASBT) siRNA or an ASBT antagonist. These findings demonstrated
      for the first time that the nontransportable tomato seed steroidal saponin,
      tomatoside A, suppressed GLUT2 expression via PKC signaling pathway during the
      ASBT-influx/MRP2-efflux process in Caco-2 cells.

PMID- 29355318
TI  - Design, Synthesis, and Antitobacco Mosaic Virus Activity of Water-Soluble Chiral
      Quaternary Ammonium Salts of Phenanthroindolizidines Alkaloids.
AB  - To study the influence of the substituent at the N-10 position on antiviral
      activity, the chiral quaternary ammonium salt derivatives of R- and S-tylophorine
      were designed, synthesized, and evaluated for antiviral activity against tobacco
      mosaic virus (TMV). The bioassay results indicated that most of the designed
      structural analogues showed good in vivo anti-TMV activity, among which propargyl
      quaternary ammonium salt compound S-7b showed the best anti-TMV activities
      (80.5%, 77.6%, 76.6%, 82.1%) at 500 MUg/mL both in vitro and in vivo in the
      laboratory. In the field trials of antiviral efficacy against TMV, S-7b as well
      exhibited better activities than control plant virus inhibitors. The stability of
      compound S-7b was obviously increased, and its solubility was more than 500-times
      higher than that of S-tylophorine. Therefore, chiral quaternary ammonium salt S
      7b was expected to be developed as a promising candidate as an inhibitor of plant
      virus.

PMID- 29355319
TI  - Recurrent Neural Network Model for Constructive Peptide Design.
AB  - We present a generative long short-term memory (LSTM) recurrent neural network
      (RNN) for combinatorial de novo peptide design. RNN models capture patterns in
      sequential data and generate new data instances from the learned context. Amino
      acid sequences represent a suitable input for these machine-learning models.
      Generative models trained on peptide sequences could therefore facilitate the
      design of bespoke peptide libraries. We trained RNNs with LSTM units on pattern
      recognition of helical antimicrobial peptides and used the resulting model for de
      novo sequence generation. Of these sequences, 82% were predicted to be active
      antimicrobial peptides compared to 65% of randomly sampled sequences with the
      same amino acid distribution as the training set. The generated sequences also
      lie closer to the training data than manually designed amphipathic helices. The
      results of this study showcase the ability of LSTM RNNs to construct new amino
      acid sequences within the applicability domain of the model and motivate their
      prospective application to peptide and protein design without the need for the
      exhaustive enumeration of sequence libraries.

PMID- 29355320
TI  - Polyketides from the Deep-Sea-Derived Fungus Graphostroma sp. MCCC 3A00421 Showed
      Potent Antifood Allergic Activities.
AB  - To discover antifood allergic components from deep-sea-derived microorganisms, we
      performed a systematic chemical investigation of the Atlantic hydrothermal fungus
      Graphostroma sp. MCCC 3A00421. Consequently, nine new (1-9) and 19 known (10-28)
      polyketides were isolated. The planar structures of the new compounds were
      elucidated mainly by detailed analysis of their nuclear magnetic resonance and
      high-resolution electrospray ionization mass spectrometry data, while the
      absolute configurations were established using the modified Mosher's method in
      association with electronic circular dichroism spectra. Graphostrin A (1) is a
      novel chlorinated polyketide derivate bearing an oxazole moiety. All isolates
      were tested for antifood allergic bioactivities in immunoglobulin E-mediated rat
      basophilic leukemia-2H3 cells. Reticulol (10) significantly decreased the rates
      of degranulation and histamine release with IC50 values of 13.5 and 13.7 MUM,
      respectively, suggesting reticulol could be a potential antifood allergic
      medicine.

PMID- 29355321
TI  - Copper-Promoted Regioselective Synthesis of Polysubstituted Pyrroles from
      Aldehydes, Amines, and Nitroalkenes via 1,2-Phenyl/Alkyl Migration.
AB  - The facile copper-catalyzed synthesis of polysubstituted pyrroles from aldehydes,
      amines, and beta-nitroalkenes is reported. Remarkably, the use of alpha-methyl
      substituted aldehydes provides efficient access to a series of tetra- and
      pentasubstituted pyrroles via an overwhelming 1,2-phenyl/alkyl migration. The
      present methodology is also accessible to non alpha-substituted aldehydes,
      yielding the corresponding trisubstituted pyrroles. On the contrary, the use of
      ketones, in place of aldehydes, does not promote the organic transformation,
      signifying the necessity of alpha-substituted aldehydes. The reaction proceeds
      under mild catalytic conditions with low catalyst loading (0.3-1 mol %), a broad
      scope, very good functional-group tolerance, and high yields and can be easily
      scaled up to more than 3 mmol of product, thus highlighting a useful synthetic
      application of the present catalytic protocol. Based on formal kinetic studies, a
      possible radical pathway is proposed that involves the formation of an allylic
      nitrogen radical intermediate, which in turn reacts with the nitroalkene to yield
      the desired pyrrole framework via a radical 1,2-phenyl or alkyl migration.

PMID- 29355322
TI  - Neuroprotective Dihydroagarofuran Sesquiterpene Derivatives from the Leaves of
      Tripterygium wilfordii.
AB  - Thirteen dihydroagarofuran derivatives, including 12 new sesquiterpenoid esters
      and one known sesquiterpenoid alkaloid, were obtained from the leaves of
      Tripterygium wilfordii. Spectroscopic techniques and the ECD method were used for
      the structure elucidation of the compounds. The structures of compounds 1 and 8
      were confirmed by single-crystal X-ray crystallographic analyses. Compounds 8, 9,
      11, 12, and 13 increased cell viability of the okadaic acid treated PC12 cells
      from 60.4 +/- 23.0% to 72.4 +/- 14.1, 71.5 +/- 11.5, 75.7 +/- 15.6, 81.2 +/-
      13.1, and 86.2 +/- 25.5% at 10 MUM, respectively.

PMID- 29355323
TI  - Salt Cluster Attachment to Crown Ether Decorated Phthalocyanines in the Gas
      Phase.
AB  - Crown ether decorated phthalocyanines were designed to form rigidly eclipsed
      aggregates with metal ions being sandwiched between the molecules. We studied
      tetra-[18]crown-6 ether functionalized zinc phthalocyanine (ZnPcTetCr) in the
      presence of excess NaCl by electrospray ionization mass spectrometry. ZnPcTetCr
      was found to form aggregates in the gas phase to which several neutral NaCl
      molecules are attached. Collision-induced dissociation experiments revealed that
      the ions observed in the positive- and negative-ion modes possess remarkably
      different structures. Their fragmentation behavior indicates that the sodium ions
      providing the charge of the positively charged aggregates are strongly bound
      inside the crown ether moieties, while the neutral salt units are less strongly
      attached. However, in the negatively charged ions, none of the sodium ions is
      embedded in the crown ether moieties, and the NaCl molecules were found to be
      attached as one large, weakly bound cluster.

PMID- 29355324
TI  - Allylic C-S Bond Construction through Metal-Free Direct Nitroalkene Sulfonation.
AB  - A metal-free, open-flask protocol was developed for the preparation of allylic
      sulfones through direct condensation of sodium arylsulfinates and beta,beta
      disubstituted nitroalkenes. The key step of this process was the Lewis base
      promoted equilibrium between nitroalkenes and allylic nitro compounds. Through
      this process, the readily available conjugated nitroalkenes can be easily
      converted into allylic nitro compounds, which contain more reactive C?C bonds
      toward the sulfonyl radical addition. As a result, allylic sulfones were prepared
      in excellent yields with a broad substrate scope under mild conditions.

PMID- 29355325
TI  - Copper-Catalyzed Diamination of Alkenes of Unsaturated Ketohydrazones with
      Amines.
AB  - A convenient copper-catalyzed intra-/intermolecular diamination of beta,gamma
      unsaturated hydrazones has been developed with simple amines as external amine
      sources. The protocol enables efficient access to various nitrogen-containing
      pyrazolines under mild reaction conditions.

PMID- 29355326
TI  - Photocatalytic Reductive Fluoroalkylation of Nitrones.
AB  - A method for the addition of fluorinated groups to nitrones using an iridium
      photocatalyst and ascorbic acid as a stoichiometric reducing agent is described.
      The reaction proceeds through the generation of fluorinated radicals by single
      electron reduction of fluorinated alkyl iodides with an iridium complex mediated
      by visible light. Besides perfluorinated reagents, partially fluorinated alkyl
      iodides can also be effectively used leading to the products, which cannot be
      obtained by conventional nucleophilic addition reactions. The resulting
      hydroxylamines can be readily converted to valuable fluorinated amines by
      reduction with zinc.

PMID- 29355327
TI  - Synthesis of Tellurabenziporphyrin and Its Pd(II) Complex.
AB  - An unprecedented tellurabenziporphyrin containing C, N, and Te donor atoms was
      synthesized by condensing benzitripyrrane and tellurophene diol under acid
      catalyzed conditions. The tellurabenziporphyrin readily forms a Pd(II) complex
      when treated with PdCl2 in CHCl3/CH3CN. The crystal structures of
      tellurabenziporphyrin and its Pd(II) complex revealed that the benzene ring
      hinders the pi-electron delocalization. An unusual five-membered ring formed
      inside the macrocycle due to the strong interaction between "Te" and "N" in the
      Pd(II) complex.

PMID- 29355328
TI  - Cajanusflavanols A-C, Three Pairs of Flavonostilbene Enantiomers from Cajanus
      cajan.
AB  - Three pairs of new flavonostilbene enantiomers, cajanusflavanols A-C (1-3), along
      with their putative biogenetic precursors 4-6, were isolated from Cajanus cajan.
      Compound 1 possesses an unprecedented carbon skeleton featuring a unique highly
      functionalized cyclopenta[1,2,3-de]isobenzopyran-1-one tricyclic core. Compounds
      2 and 3 are the first examples of methylene-unit-linked flavonostilbenes. Their
      structures with absolute configurations were elucidated by spectroscopic
      analyses, X-ray diffraction, and computational calculations. Compounds 1 and 2
      exhibited significant in vitro anti-inflammatory activities.

PMID- 29355329
TI  - Remote Asymmetric Oxa-Diels-Alder Reaction of 5-Allylic Furfurals via
      Dearomatizative Tetraenamine Catalysis.
AB  - A previously unreported activation mode is developed through the generation of
      dearomatizative tetraenamine species between 5-allylic furfurals and a
      bifunctional amine-thiourea catalyst. The very remote zeta,eta-alkenes perform as
      effective HOMO-raised dienophiles in inverse-electron-demand oxa-Diels-Alder
      cycloadditions with isatin-derived oxadiene substrates, delivering
      multifunctional spirocyclic oxindoles incorporating a dihydropyran skeleton in
      moderate to high yields with good to excellent enantio- and diastereoselectivity.

PMID- 29355330
TI  - Synthesis of Quinolizinium-Type Heteroaromatics via a Carbene Intermediate.
AB  - An efficient synthesis of quinolizinium-type heteroaromatics by Pt(II)-catalyzed
      cyclization of 2-arylpyridine propargyl alcohol has been developed. The presence
      of a protic acid is crucial for the success of the reaction. Mechanistic studies
      disclosed that the reaction proceeds via a platinum-carbene intermediate.
      Additionally, the fluorescence properties of the synthesized heteroaromatics were
      investigated to provide perspectives for potential applications.

PMID- 29355331
TI  - A qualitative examination of contextual influences on negative alcohol
      consequence evaluations among young adult drinkers.
AB  - Alcohol misuse and associated negative consequences experienced by college
      students persists as a public health concern. Quantitative studies demonstrate
      variability in subjective evaluations of consequences, and how positively or
      negatively consequences are evaluated is associated with drinking behavior.
      Lacking is a qualitative exploration of how drinkers evaluate consequences and
      what influences those evaluations. We conducted a series of single-gender focus
      groups (13 groups; 3-7 per group; n = 62, 48% female) with college student
      drinkers. Questions focused on: (a) types of negative and positive consequences
      experienced (b) personal perceptions of negative consequences and (c) factors
      influencing those perceptions. Verbatim transcripts were content analyzed using
      applied thematic analysis with NVivo software. Several negative consequences not
      included in current assessment tools emerged. Reactions to these "negative"
      consequences of alcohol misuse were not labeled as uniformly negative by
      participants. Contextual influences on reactions to consequences included: social
      factors (e.g., normative perceptions, social context, discussions with friends),
      level of intoxication, concurrent positive consequences, time, and alcohol as an
      excuse. Future research should focus on consequence measure development and
      examine interactions between contextual and individual influences on subjective
      consequence evaluations. (PsycINFO Database Record

PMID- 29355332
TI  - Delay discounting of losses and rewards in alcohol use disorder: The effect of
      working memory load.
AB  - Alcohol use disorder (AUD) has been consistently associated with elevated
      discounting rates for delayed rewards. However, there are few studies of delay
      discounting of losses in those with AUD even though their drinking behavior
      suggests that they discount future negative consequences of excessive drinking.
      The current study extends this literature by examining delay discounting of
      rewards and losses in a sample of those with AUD (n = 78) and healthy controls (n
      = 51) in 2 conditions: working memory (WM) load and no WM load. The AUD group
      discounted both rewards and losses at higher rates than the control group. The WM
      load increased discounting rates in the reward task but not in the loss task.
      There was also a significant Group * WM load interaction; the WM load increased
      discounting in control participants but not in AUD participants. These findings
      suggest that AUD is associated with a general propensity to discount future
      incentivized events regardless of nature of the incentive. (PsycINFO Database
      Record

PMID- 29355333
TI  - Acculturation and alcohol use among Asian Americans: A meta-analytic review.
AB  - Acculturation has been considered a key sociocultural factor that helps explain
      Asian American's mental health outcomes, including alcohol use. Yet, findings on
      the degree to which acculturation is directly linked to alcohol use have been
      mixed. The present meta-analysis reviewed original studies published since 1979,
      and tested the association between acculturation and alcohol use outcomes among
      Asian Americans across age groups. Analyses also examined the extent to which
      participant and methodological variables moderated this relation. A systematic
      literature review yielded 31 published research reports that were eligible for
      the meta-analysis. Across 39 independent study samples (N = 28,028), analysis
      with random-effects model estimated a small and statistically significant mean
      weighted correlation between acculturation and alcohol use (r = .06, p < .05).
      Acculturation appeared to be more robustly associated with alcohol consumption
      and intensity of hazardous alcohol use, but not drinking-related problems. Most
      studies examined acculturation as a unidimensional construct. Within study
      samples that conceptualized acculturation as a bidimensional construct, alcohol
      use was positively associated with acculturation (orientation to the mainstream
      host culture) but negatively associated with enculturation (orientation to the
      Asian heritage culture). Statistically significant between-study variability
      (Q[38] = 876.62, p < .001, I2 = 95.67%) was accounted for by gender, age, and
      geographical location. Limitations to the scope of this meta-analysis regarding
      the observational nature of study effect sizes, sample-level analyses, and focus
      on self-report survey data, as well as future research directions are discussed.
      (PsycINFO Database Record

PMID- 29355334
TI  - Schizophrenia, narrative, and neurocognition: The utility of life-stories in
      understanding social problem-solving skills.
AB  - OBJECTIVE: Schizophrenia researchers have focused on phenomenological aspects of
      the disorder to better understand its underlying nature. In particular,
      development of personal narratives-that is, the complexity with which people
      form, organize, and articulate their "life stories"-has recently been
      investigated in individuals with schizophrenia. However, less is known about how
      aspects of narrative relate to indicators of neurocognitive and social
      functioning. The objective of the present study was to investigate the
      association of linguistic complexity of life-story narratives to measures of
      cognitive and social problem-solving abilities among people with schizophrenia.
      METHOD: Thirty-two individuals with a diagnosis of schizophrenia completed a
      research battery consisting of clinical interviews, a life-story narrative,
      neurocognitive testing, and a measure assessing multiple aspects of social
      problem solving. Narrative interviews were assessed for linguistic complexity
      using computerized technology. RESULTS: The results indicate differential
      relationships of linguistic complexity and neurocognition to domains of social
      problem-solving skills. More specifically, although neurocognition predicted how
      well one could both describe and enact a solution to a social problem, linguistic
      complexity alone was associated with accurately recognizing that a social problem
      had occurred. In addition, linguistic complexity appears to be a cognitive factor
      that is discernible from other broader measures of neurocognition. CONCLUSIONS
      AND IMPLICATIONS FOR PRACTICE: Linguistic complexity may be more relevant in
      understanding earlier steps of the social problem-solving process than more
      traditional, broad measures of cognition, and thus is relevant in conceptualizing
      treatment targets. These findings also support the relevance of developing
      narrative-focused psychotherapies. (PsycINFO Database Record

PMID- 29355336
TI  - Decreases in psychological well-being among American adolescents after 2012 and
      links to screen time during the rise of smartphone technology.
AB  - In nationally representative yearly surveys of United States 8th, 10th, and 12th
      graders 1991-2016 (N = 1.1 million), psychological well-being (measured by self
      esteem, life satisfaction, and happiness) suddenly decreased after 2012.
      Adolescents who spent more time on electronic communication and screens (e.g.,
      social media, the Internet, texting, gaming) and less time on nonscreen
      activities (e.g., in-person social interaction, sports/exercise, homework,
      attending religious services) had lower psychological well-being. Adolescents
      spending a small amount of time on electronic communication were the happiest.
      Psychological well-being was lower in years when adolescents spent more time on
      screens and higher in years when they spent more time on nonscreen activities,
      with changes in activities generally preceding declines in well-being. Cyclical
      economic indicators such as unemployment were not significantly correlated with
      well-being, suggesting that the Great Recession was not the cause of the decrease
      in psychological well-being, which may instead be at least partially due to the
      rapid adoption of smartphones and the subsequent shift in adolescents' time use.
      (PsycINFO Database Record

PMID- 29355337
TI  - Managing the harmful effects of unsupportive organizations during pregnancy.
AB  - Unfortunately, not all organizations are supportive of employees' family lives.
      Family unsupportive workplaces can be stressful for all employees and
      particularly for pregnant women, who carry a physical reminder of their family
      life. In the present study, we draw on conservation of resources (COR) theory
      (Hobfoll, 1989, 2001) to investigate how women manage family unsupportive
      organizational perceptions during pregnancy via social identity-based impression
      management behaviors as well as how these strategies relate to changes in stress
      and changes in conflict between work and family. Specifically, we find that image
      maintenance strategies-impression management strategies aimed at maintaining
      one's prepregnancy image-are associated with decreases in work stress and work
      family conflict over the course of pregnancy, while decategorization-impression
      management strategies aimed at avoiding negative outcomes by hiding the pregnancy
      or dodging the issue-are related to increases in work-family conflict. These
      results suggest strategies for both organizations and pregnant workers to
      decrease stress during a time when health is vital for both mother and baby.
      (PsycINFO Database Record

PMID- 29355335
TI  - The neuroscience of cognitive-motivational styles: Sign- and goal-trackers as
      animal models.
AB  - Cognitive-motivational styles describe predominant patterns of processing or
      biases that broadly influence human cognition and performance. Here we focus on
      the impact of cognitive-motivational styles on the response to cues predicting
      the availability of food or addictive drugs. An individual may preferably conduct
      an analysis of the motivational significance of reward cues, with the result that
      such cues per se are perceived as rewarding and worth approaching and working
      for. Alternatively, a propensity for a "cold" analysis of the behavioral utility
      of a reward cue may yield search behavior for food or drugs but not involve cue
      approach. Animal models for studying the neuronal mechanisms mediating such
      styles have originated from research concerning behavioral indices that predict
      differential vulnerability to addiction-like behaviors. Rats classified as sign-
      or goal-trackers (STs, GTs) were found to have opposed attentional biases (bottom
      up or cue-driven attention vs. top-down or goal-driven attentional control) that
      are mediated primarily via relatively unresponsive versus elevated levels of
      cholinergic neuromodulation in the cortex. The capacity for cholinergic
      neuromodulation in STs is limited by a neuronal choline transporter (CHT) that
      fails to support increases in cholinergic activity. Moreover, in contrast to STs,
      the frontal dopamine system in GTs does not respond to the presence of drug cues
      and, thus, biases against cue-oriented behavior. The opponent cognitive
      motivational styles that are indexed by sign- and goal-tracking bestow different
      cognitive-behavioral vulnerabilities that may contribute to the manifestation of
      a wide range of neuropsychiatric disorders. (PsycINFO Database Record

PMID- 29355338
TI  - Understanding the dark and bright sides of anxiety: A theory of workplace
      anxiety.
AB  - Researchers have uncovered inconsistent relations between anxiety and
      performance. Although the prominent view is a "dark side," where anxiety has a
      negative relation with performance, a "bright side" of anxiety has also been
      suggested. We reconcile past findings by presenting a comprehensive multilevel,
      multiprocess model of workplace anxiety called the theory of workplace anxiety
      (TWA). This model highlights the processes and conditions through which workplace
      anxiety may lead to debilitative and facilitative job performance and includes 19
      theoretical propositions. Drawing on past theories of anxiety, resource
      depletion, cognitive-motivational processing, and performance, we uncover the
      debilitative and facilitative nature of dispositional and situational workplace
      anxiety by positioning emotional exhaustion, self-regulatory processing, and
      cognitive interference as distinct contrasting processes underlying the
      relationship between workplace anxiety and job performance. Extending our
      theoretical model, we pinpoint motivation, ability, and emotional intelligence as
      critical conditions that shape when workplace anxiety will debilitate and
      facilitate job performance. We also identify the unique employee, job, and
      situational characteristics that serve as antecedents of dispositional and
      situational workplace anxiety. The TWA offers a nuanced perspective on workplace
      anxiety and serves as a foundation for future work. (PsycINFO Database Record

PMID- 29355339
TI  - The downside of downtime: The prevalence and work pacing consequences of idle
      time at work.
AB  - Although both media commentary and academic research have focused much attention
      on the dilemma of employees being too busy, this paper presents evidence of the
      opposite phenomenon, in which employees do not have enough work to fill their
      time and are left with hours of meaningless idle time each week. We conducted six
      studies that examine the prevalence and work pacing consequences of involuntary
      idle time. In a nationally representative cross-occupational survey (Study 1), we
      found that idle time occurs frequently across all occupational categories; we
      estimate that employers in the United States pay roughly $100 billion in wages
      for time that employees spend idle. Studies 2a-3b experimentally demonstrate that
      there are also collateral consequences of idle time; when workers expect idle
      time following a task, their work pace declines and their task completion time
      increases. This decline reverses the well-documented deadline effect, producing a
      deadtime effect, whereby workers slow down as a task progresses. Our analyses of
      work pace patterns provide evidence for a time discounting mechanism: workers
      discount idle time when it is relatively distant, but act to avoid it
      increasingly as it becomes more proximate. Finally, Study 4 demonstrates that the
      expectation of being able to engage in leisure activities during posttask free
      time (e.g., surfing the Internet) can mitigate the collateral work pace losses
      due to idle time. Through examination and discussion of the effects of idle time
      at work, we broaden theory on work pacing. (PsycINFO Database Record

PMID- 29355341
TI  - Toward customer-centric organizational science: A common language effect size
      indicator for multiple linear regressions and regressions with higher-order
      terms.
AB  - To address a long-standing concern regarding a gap between organizational science
      and practice, scholars called for more intuitive and meaningful ways of
      communicating research results to users of academic research. In this article, we
      develop a common language effect size index (CLbeta) that can help translate
      research results to practice. We demonstrate how CLbeta can be computed and used
      to interpret the effects of continuous and categorical predictors in multiple
      linear regression models. We also elaborate on how the proposed CLbeta index is
      computed and used to interpret interactions and nonlinear effects in regression
      models. In addition, we test the robustness of the proposed index to violations
      of normality and provide means for computing standard errors and constructing
      confidence intervals around its estimates. (PsycINFO Database Record

PMID- 29355340
TI  - Prosocial response to client-instigated victimization: The roles of forgiveness
      and workgroup conflict.
AB  - We investigate forgiveness as a human service employee coping response to client
      instigated victimizations and further explore the role of workgroup conflict in
      (a) facilitating this response, and (b) influencing the relationship between
      victimization and workplace outcomes. Using the theoretical lens of Conservation
      of Resources (Hobfoll, 1989), we propose that employees forgive clients
      especially in the context of low workgroup conflict. From low to moderate levels
      of client-instigated victimization, we suggest that victimization and forgiveness
      are positively related; however, this positive relationship does not prevail when
      individuals confront egregious levels of victimization (i.e., an inverted-U
      shape). This curvilinear relationship holds under low but not under high
      workgroup conflict. Extending this model to workplace outcomes, findings also
      demonstrate that the indirect effects of victimization on job satisfaction,
      burnout, and turnover intentions are mediated by forgiveness when workgroup
      conflict is low. Experiment- and field-based studies provide evidence for the
      theoretical model. (PsycINFO Database Record

PMID- 29355342
TI  - "I don't care about you as a person": Sexual minority women objectified.
AB  - This study investigates sexual minority women's experiences of objectification in
      the United States. Data from 5 focus groups with 33 sexual minority women were
      analyzed using thematic analysis (Braun & Clarke, 2006, 2012). Results revealed 6
      themes and 34 subthemes grouped into "manifestations of objectification: general
      and explicit intersections," "immediate context of relational and situational
      characteristics," and "broader context of oppression and privilege along gender
      and sexualities." First, sexual minority women's experiences of objectification
      included both general manifestations described in prior research with
      heterosexual women and manifestations of objectification that reflected
      intersections of systems of inequality based on sexual orientation, gender
      identity, race, ethnicity, culture, and age. Second, participants identified
      novel relational and situational characteristics of objectification. Finally,
      participants included experiences of stereotyping, discrimination, and
      dehumanization in their conceptualizations of objectification, connecting their
      experiences of objectification with broader dynamics of power related to gender
      and sexuality. Centralizing sexual minority women's experiences, this study
      produced a fuller understanding of objectification experiences in general and of
      sexual minority women's experiences in particular. (PsycINFO Database Record

PMID- 29355343
TI  - Predictors of science, technology, engineering, and mathematics choice options: A
      meta-analytic path analysis of the social-cognitive choice model by gender and
      race/ethnicity.
AB  - We tested the interest and choice portion of social-cognitive career theory
      (SCCT; Lent, Brown, & Hackett, 1994) in the context of science, technology,
      engineering, and mathematics (STEM) domains. Data from 143 studies (including 196
      independent samples) conducted over a 30-year period (1983 through 2013) were
      subjected to meta-analytic path analyses. The interest/choice model was found to
      fit the data well over all samples as well as within samples composed primarily
      of women and men and racial/ethnic minority and majority persons. The model also
      accounted for large portions of the variance in interests and choice goals within
      each path analysis. Despite the general predictive utility of SCCT across gender
      and racial/ethnic groups, we did find that several parameter estimates differed
      by group. We present both the group similarities and differences and consider
      their implications for future research, intervention, and theory refinement.
      (PsycINFO Database Record

PMID- 29355345
TI  - Attachment avoidance, alexithymia, and gender: Examining their associations with
      distress disclosure tendencies and event-specific disclosure.
AB  - Distress disclosure has been linked with reduced psychological distress,
      increased wellbeing, and successful psychotherapeutic outcome. Because of the
      importance of distress disclosure, researchers have worked to develop and improve
      theoretical models of disclosure to facilitate counseling practices that reduce
      impediments to disclosure. Presently, we conducted a 2-part study to investigate
      distress disclosure's associations with attachment avoidance, gender, and
      alexithymia-3 constructs frequently linked with disclosure. In Part 1, we
      examined the extent to which attachment avoidance, alexithymia, and gender
      predicted general disclosure tendencies. In Part 2, we examined the extent to
      which attachment avoidance, alexithymia, and gender predicted event-specific
      disclosure. Participants were recruited from a crowdsourcing website (N = 178 in
      Part 1; N = 108 in Part 2). In Part 1, alexithymia partially mediated the
      association between attachment avoidance and disclosure tendencies, and the link
      between attachment avoidance and alexithymia was stronger for men than women. In
      Part 2, the association between distress intensity and event-specific disclosure
      was weaker for people with high levels of alexithymia. Implications for
      counseling theory and practice are discussed. (PsycINFO Database Record

PMID- 29355344
TI  - Emotional congruence between clients and therapists and its effect on treatment
      outcome.
AB  - The present study aimed to (a) explore 2 indices of emotional congruence-temporal
      similarity and directional discrepancy-between clients' and therapists' ratings
      of their emotions as they cofluctuate session-by-session; and (b) examine whether
      client/therapist emotional congruence predicts clients' symptom relief and
      improved functioning. The sample comprised 109 clients treated by 62 therapists
      in a university setting. Clients and therapists self-reported their negative (NE)
      and positive emotions (PE) after each session. Symptom severity and functioning
      level were assessed at the beginning of each session using the clients' self
      reports. To assess emotional congruence, an adaptation of West and Kenny's (2011)
      Truth and Bias model was applied. To examine the consequences of emotional
      congruence, polynomial regression, and response surface analyses were conducted
      (Edwards & Parry, 1993). Clients and therapists were temporally similar in both
      PE and NE. Therapists experienced less intense PE on average, but did not
      experience more or less intense NE than their clients. Those therapists who
      experienced more intense NE than their clients were more temporally similar in
      their emotions to their clients. Therapist/client incongruence in both PE and NE
      predicted poorer next-session symptomatology; incongruence in PE was also
      associated with lower client next-session functioning. Session-level symptoms
      were better when therapists experienced more intense emotions (both PE and NE)
      than their clients. The findings highlight the importance of recognizing the
      dynamic nature of emotions in client-therapist interactions and the contribution
      of session-by-session emotional dynamics to outcomes. (PsycINFO Database Record

PMID- 29355346
TI  - Mental Help Seeking Attitudes Scale (MHSAS): Development, reliability, validity,
      and comparison with the ATSPPH-SF and IASMHS-PO.
AB  - Attitudes is a key help-seeking construct that influences treatment seeking
      behavior via intention to seek help, per the theory of planned behavior (TPB).
      This article presents the development and psychometric evaluation of the Mental
      Help Seeking Attitudes Scale (MHSAS), designed to measure respondents' overall
      evaluation (unfavorable vs. favorable) of their seeking help from a mental health
      professional. In Study 1 (N = 857 United States adults), exploratory factor
      analysis (EFA), confirmatory factor analysis (CFA), and item response theory
      (IRT) analysis were used to identify an optimal set of 9 items that demonstrated
      initial evidence of internal consistency, unidimensionality, and strong
      measurement equivalence/invariance (ME/I) across gender, past help-seeking
      experience, and psychological distress. Initial convergent evidence of validity
      was demonstrated via theoretically anticipated relationships between the MHSAS
      and key variables in the help-seeking nomological network (e.g., subjective
      norms, perceived behavioral control, intention, public stigma, self-stigma,
      anticipated risks and benefits, gender, previous help seeking). Initial
      incremental evidence of validity was demonstrated when the MHSAS demonstrated the
      ability to account for unique variance in help-seeking intention, beyond that
      accounted for by the Attitudes Toward Seeking Professional Psychological Help
      Short Form scale (ATSPPH-SF) and the Psychological Openness subscale of the
      Inventory of Attitudes Toward Seeking Mental Health Services (IASMHS-PO). Study 2
      (N = 207 United States adults at Times 1 and 2) provided initial evidence of test
      retest reliability over a 3-week period. The MHSAS offers mental health
      professionals a new tool for measuring attitudes that may avoid limitations of
      current help seeking-attitudes measures (e.g., construct-irrelevant variance).
      (PsycINFO Database Record

PMID- 29355347
TI  - Emotions in everyday life during social movements: Prospective predictions of
      mental health.
AB  - Emotion mobilizes and demobilizes a social movement while the movement itself
      impacts people's emotions. An evidence base is needed for developing timely
      emotion-focused counseling services for affected populations worldwide. This
      experience sampling study investigated the impact of a social movement on
      everyday emotional reactivity, variability, instability, and persistence, and
      whether and how these predicted subsequent psychological distress and well-being
      among 108 community-dwelling adults. Fifty-four participants reported momentary
      events and emotions 5 times daily over 7 days during the Umbrella Movement in
      Hong Kong. An age-matched, sex-matched comparison group (n = 54) participated
      during a period without major social/political movement. Psychological distress
      and well-being were assessed at baseline (Time 1 [T1]) and 3-month follow-up
      (Time 2 [T2]). Hierarchical linear modeling revealed lower valence ratings of
      positive events during the Umbrella Movement. Lower positive emotional reactivity
      and higher negative emotional reactivity in positive events were reported during
      the movement. Controlling for demographics and T1 scores, the positive
      association between negative emotional reactivity in positive events and T2
      depressive symptoms, and the inverse association between positive emotional
      instability and T2 positive emotions, were significant only among the comparison
      group. The positive association between positive emotions in positive events and
      T2 life satisfaction was significant only among the Umbrella Movement group.
      People could experience significant changes in their emotions in everyday life
      during a social movement, even if it is short and relatively nonviolent like the
      Umbrella Movement. Maximizing positive emotions in positive events during a
      social movement can uniquely contribute to higher subsequent psychological well
      being. (PsycINFO Database Record

PMID- 29355349
TI  - Faster alcohol metabolism is associated with increased stimulation and within
      session consumption.
AB  - Variability in subjective response (SR) to alcohol predicts drinking and the
      development of Alcohol Use Disorders (AUDs). Although both alcohol
      pharmacokinetics (i.e., absorption and metabolism) and SR are impacted by aspects
      of the drinking situation (e.g., rate of consumption), relations between
      individual differences in pharmacokinetics and SR have received little attention.
      The current study examined the extent to which alcohol pharmacokinetics impact SR
      and drinking during a single alcohol administration session. A total of 119 (67%
      male) social drinkers were administered a dose of alcohol with a target blood
      alcohol concentration (BAC) of 0.08g%. The Biphasic Alcohol Effects Scale was
      administered twice at matched ascending and descending limb BACs following
      alcohol consumption to assess SR. Pharmacokinetic properties (absorption and
      metabolism) were inferred using multiple BAC readings to calculate the area under
      the curve during the ascending limb (absorption) and descending limb
      (metabolism). Following completion of SR measures, an ad libitum taste rating
      task utilizing nonalcoholic beer was implemented to assess voluntary 'alcohol'
      consumption. Results indicated that participants who metabolized alcohol more
      quickly maintained a greater level of subjective stimulation on the descending
      limb. Faster metabolism was indirectly related to ad lib nonalcoholic beer
      consumption through greater maintenance of stimulant effects. Absorption did not
      significantly predict SR or within session drinking. The results increase
      understanding of SR variability and suggest that heightened stimulation that is
      sustained across limbs of the BAC curve may increase risk for excessive
      consumption. Individual differences in alcohol metabolism may be an identifiable
      biomarker of this high risk pattern of SR. (PsycINFO Database Record

PMID- 29355348
TI  - Access to environmental reward mediates the relation between posttraumatic stress
      symptoms and alcohol problems and craving.
AB  - Symptoms of posttraumatic stress (PTS) show significant comorbidity with alcohol
      use, but little is known about the mechanisms that might account for this
      comorbidity. Deficits in reward functioning have long been implicated in alcohol
      misuse and more recently in PTS reactions, but no study has examined whether
      reward deprivation may serve as a transdiagnostic risk factor for comorbid PTS
      alcohol misuse. The current cross-sectional study sought to test the behavioral
      economic hypothesis that reward deprivation would be related to both PTS symptoms
      and alcohol problems, and would mediate the relation between PTS symptoms and
      alcohol problems in college students. We recruited a diverse sample of urban
      college students (N = 203, Mage = 21.5 years, SD = 5.5; 79.5% female; 56.8%
      White, 28.1% Black, .9% Asian, 9.8% Multiracial) who endorsed both alcohol use
      and PTS symptoms. Reward deprivation (lack of access to, and ability to,
      experience reward) was related to alcohol problems, and a lack of access to
      reward was related to PTS symptoms. Furthermore, reward access mediated the
      relation between PTS symptoms and alcohol problems and craving, after controlling
      for alcohol use, age, gender, and race. These data provide preliminary support
      for behavioral economic models of alcohol comorbidity and suggest that treatments
      for combined PTS and alcohol misuse should attempt to reduce barriers to
      accessing natural rewards. (PsycINFO Database Record

PMID- 29355350
TI  - Allocating under the influence: Effects of alcohol intoxication and social
      identification on in-group favoritism.
AB  - The "social lubrication" function of alcohol during interpersonal interactions is
      well documented. However, less is known about the effects of alcohol consumption
      on group-level behavior. Empirical findings from social psychological literature
      suggest that individuals tend to favor those who are considered as members of
      their own social group. Not yet evaluated is how alcohol intoxication interacts
      with this group-level bias. Therefore, the current study examined experimentally
      the effects of intoxication on group bias. Ninety-four individuals (Mage = 20.18,
      SD = 2.36, 55 women, 39 men) were randomly assigned to consume an alcoholic (n =
      48) or a placebo (n = 46) drink before completing manipulated allocation
      matrices, a task which measured the distribution of hypothetical monetary awards
      based on social groups. Results point to an interaction between drink condition
      and social group identification, whereby identification was significantly
      associated with in-group favoritism among intoxicated individuals only. Following
      alcohol consumption, participants with higher identification with their social
      group were more likely to demonstrate allocation strategies that favored their
      own group members. However, nonsignificant effects were observed for those in the
      placebo condition. The findings highlight how alcohol intoxication may facilitate
      group bias that results from social group identification. (PsycINFO Database
      Record

PMID- 29355351
TI  - Happy hour drink specials in the Alcohol Purchase Task.
AB  - There is strong evidence to suggest that happy hour drink specials are associated
      with undesirable outcomes such as increased amount of drinking, increased
      likelihood of being highly intoxicated, and increased likelihood of experiencing
      negative outcomes related to drinking (e.g., getting into fights). Public policy
      efforts have been made to ban or at least restrict alcohol drink specials.
      Research in behavioral economics-primarily demand curve analyses-has yielded
      valuable insights into the role of environmental effects on reinforcer
      consumption, especially within the context of alcohol reinforcement. The use of
      the Alcohol Purchase Task (APT), which asks respondents to report how many
      alcoholic drinks they would be willing to purchase at various prices, has
      contributed greatly to these efforts. The purpose of the current experiment was
      to determine whether self-reported consumption of alcohol on an APT changes when
      participants imagine a hypothetical "happy hour" scenario, akin to drink specials
      encountered in the real world. Results from the current experiment extend
      previous literature on APT vignette manipulations and provide implications for
      efforts to reduce problematic drinking. (PsycINFO Database Record

PMID- 29355353
TI  - Do we overemphasize the role of culture in the behavior of racial/ethnic
      minorities? Evidence of a cultural (mis)attribution bias in American psychology.
AB  - Although culture influences all human beings, there is an assumption in American
      psychology that culture matters more for members of certain groups. This article
      identifies and provides evidence of the cultural (mis)attribution bias: a
      tendency to overemphasize the role of culture in the behavior of racial/ethnic
      minorities, and to underemphasize it in the behavior of Whites. Two studies
      investigated the presence of this bias with an examination of a decade of peer
      reviewed research conducted in the United States (N = 434 articles), and an
      experiment and a survey with psychology professors in the United States (N = 361
      psychologists). Archival analyses revealed differences in the composition of
      samples used in studies examining cultural or noncultural psychological
      phenomena. We also find evidence to suggest that psychologists in the United
      States favor cultural explanations over psychological explanations when
      considering the behavior and cognition of racial/ethnic minorities, whereas the
      opposite pattern emerged in reference to Whites. The scientific ramifications of
      this phenomenon, as well as alternatives to overcome it, are discussed in detail.
      (PsycINFO Database Record

PMID- 29355352
TI  - Community-based participatory research (CBPR): Towards equitable involvement of
      community in psychology research.
AB  - Community-based participatory research (CBPR) answers the call for more patient
      centered, community-driven research approaches to address growing health
      disparities. CBPR is a collaborative research approach that equitably involves
      community members, researchers, and other stakeholders in the research process
      and recognizes the unique strengths that each bring. The aim of CBPR is to
      combine knowledge and action to create positive and lasting social change. With
      its origins in psychology, sociology, and critical pedagogy, CBPR has become a
      common research approach in the fields of public health, medicine, and nursing.
      Although it is well aligned with psychology's ethical principles and research
      aims, it has not been widely implemented in psychology research. The present
      article introduces CBPR to a general psychology audience while considering the
      unique aims of and challenges in conducting psychology research. In this article,
      we define CBPR principles, differentiate it from a more traditional psychology
      research approach, retrace its historical roots, provide concrete steps for its
      implementation, discuss its potential benefits, and explore practical and ethical
      challenges for its integration into psychology research. Finally, we provide a
      case study of CBPR in psychology to illustrate its key constructs and
      implementation. In sum, CBPR is a relevant, important, and promising research
      framework that may guide the implementation of more effective, culturally
      appropriate, socially just, and sustainable community-based psychology research.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29355354
TI  - Civilization and its discontented: Links between youth victimization, beliefs
      about government, and political participation across seven American presidencies.
AB  - Promoting trust in public officials and active political engagement is vital to
      sustaining a well-functioning democracy. Developmental psychologists propose that
      youths' beliefs about government and participation in politics are rooted in
      personal experiences within their communities. Previous studies have focused on
      how positive experiences within youths' families, schools, and communities
      facilitate greater social trust and political participation. However, less is
      known about how negative interpersonal experiences-such as criminal victimization
      intersect with youths' beliefs about the trustworthiness, competence, and
      knowledge of government officials, and their participation in political activity.
      Using data from 39 waves of the Monitoring the Future study, the current study
      examined associations among youth victimization, beliefs about government, and
      participation in various political activities. Adolescents (N = 109,574; 50.9%
      female) enrolled in 12th grade across the United States reported on whether they
      had experienced various types of victimization during the previous year, their
      beliefs about government, and their participation in multiple forms of political
      activity. Adolescents who reported more frequent victimization experiences
      endorsed significantly greater discontent with government and were significantly
      more engaged in various forms of political activity. The magnitude and direction
      of these effects were generally consistent across different types of
      victimization, different demographic subgroups of youth, and different
      sociohistorical periods. Findings are interpreted from a social contract theory
      perspective, followed by a discussion of implications for building psychological
      theory and informing public policy. (PsycINFO Database Record

PMID- 29355355
TI  - Looking for intoolligence: A unified framework for the cognitive study of human
      tool use and technology.
AB  - Humans have considerably modified their environment by making and building a
      number of tools, technologies, and constructions. This unique ability compared to
      other animals is the focus of researchers in different fields of psychology.
      However, there is confusion about the definitions proposed, generating
      difficulties in making connections between those different fields. This article
      presents the first unified framework (i.e., intoolligence) aiming to overcome
      these issues by focusing on the cognitive processes involved in the different
      forms taken by human tool use and technology, rather than on the overt behavior.
      To lay the foundation for intoolligence, we first address a series of
      epistemological misconceptions, which are the root cause for the current
      confusion. Particularly, we discuss the limitations of the widespread idea that
      tool use relies on specific cognitive skills, centered on the manipulative aspect
      of tool use. We develop, based on this analysis, details concerning our
      framework, which is based on the key principle that making and using are 2
      independent cognitive steps. This distinction allows us to redefine tool use by
      breaking it down into 3 modes: assistive tool use, arbitrary tool use, and free
      tool use. This article opens a new chapter on the topic of human tool use and
      technology. (PsycINFO Database Record

PMID- 29355356
TI  - Compelled disclosure of college sexual assault.
AB  - Sexual assault is a widespread problem on college campuses. In response, many
      institutions are developing policies mandating that certain employees report any
      student disclosure of sexual assault to university officials (and, in some cases,
      to police), with or without the survivor's consent. These policies,
      conceptualized here as compelled disclosure, have been prompted and shaped by
      federal law and guidance, including Title IX and The Clery Act. Proponents of
      compelled disclosure assert that it will increase reports-enabling universities
      to investigate and remedy more cases of sexual assault-and will benefit sexual
      assault survivors, university employees, and the institution. However, many
      questions remain unanswered. How broad (or narrowly tailored) are contemporary
      compelled disclosure mandates in higher education? Do any empirical data support
      assumptions about the benefits of these policies? Are there alternative
      approaches that should be considered, to provide rapid and appropriate responses
      to sexual violence while minimizing harm to students? The current article begins
      with an overview of federal law and guidance around compelled disclosure. Next, a
      content analysis of a stratified random sample of 150 university policies
      provides evidence that the great majority require most, if not all, employees to
      report student sexual assault disclosures. A review of the literature then
      suggests that these policies have been implemented despite limited evidence to
      support assumptions regarding their benefits and effectiveness. In fact, some
      findings suggest negative consequences for survivors, employees, and
      institutions. The article concludes with a call for survivor-centered reforms in
      institutional policies and practices surrounding sexual assault. (PsycINFO
      Database Record

PMID- 29355357
TI  - Callous-unemotional traits moderate the association between children's early
      moral understanding and aggression: A short-term longitudinal study.
AB  - Drawing on the framework of social domain theory, this multi-method, multi
      informant longitudinal study examined whether callous-unemotional (CU) tendencies
      moderated the association between U.S. 4 to 7 year olds' (n = 135; Mage = 5.65,
      50% male; 75% White) ability to differentiate hypothetical, prototypical moral
      and conventional transgressions along theoretical criteria and teacher (n = 49)
      and parent (n = 128, 91% mothers) ratings of physical aggression. Deficits in
      domain distinction ability were associated with greater teacher-reported
      aggression both concurrently and 9 months later, but only for children high in CU
      traits. No main effects or interactions were found for parent reports. These
      findings build on a growing body of research demonstrating that children who use
      aggression in a deliberate and callous manner show deficits in their basic
      understanding of moral norms. (PsycINFO Database Record

PMID- 29355358
TI  - Young children pause on phrase boundaries in self-paced music listening: The role
      of harmonic cues.
AB  - Proper segmentation of auditory streams is essential for understanding music.
      Many cues, including meter, melodic contour, and harmony, influence adults'
      perception of musical phrase boundaries. To date, no studies have examined young
      children's musical grouping in a production task. We used a musical self-pacing
      method to investigate (1) whether dwell times index young children's musical
      phrase grouping and, if so, (2) whether children dwell longer on phrase
      boundaries defined by harmonic cues specifically. In Experiment 1, we asked 3
      year-old children to self-pace through chord progressions from Bach chorales
      (sequences in which metrical, harmonic, and melodic contour grouping cues
      aligned) by pressing a computer key to present each chord in the sequence.
      Participants dwelled longer on chords in the 8th position, which corresponded to
      phrase endings. In Experiment 2, we tested 3-, 4-, and 7-year-old children's
      sensitivity to harmonic cues to phrase grouping when metrical regularity cues and
      melodic contour cues were misaligned with the harmonic phrase boundaries. In this
      case, 7 and 4 year olds but not 3 year olds dwelled longer on harmonic phrase
      boundaries, suggesting that the influence of harmonic cues on phrase boundary
      perception develops substantially between 3 and 4 years of age in Western
      children. Overall, we show that the musical dwell time method is child-friendly
      and can be used to investigate various aspects of young children's musical
      understanding, including phrase grouping and harmonic knowledge. (PsycINFO
      Database Record

PMID- 29355359
TI  - Developmental processes across the first two years of parenthood: Stability and
      change in adult attachment style.
AB  - The first months after becoming a new parent are a unique and important period in
      human development. Despite substantial research on the many social and biological
      changes that occur during the first months of parenthood, little is known about
      changes in mothers' attachment. The present study examines developmental
      stability and change in first-time mothers' attachment style across the first 2
      years of motherhood. At Time 1, 162 economically stressed primiparous mothers
      (Mage = 23.98 years, SD = 5.18) completed measures of attachment anxiety and
      avoidance at five time points: when their children were 0, 6, 12, 18, and 24
      months of age. Converging results of stability functions and latent growth curve
      models suggest that attachment styles were generally stable during the first 2
      years of motherhood, even in this economically stressed sample. Furthermore,
      model comparisons revealed that a prototype model better characterized the
      developmental dynamics of mothers' attachment style than did a revisionist model,
      consistent with previous studies of adults and adolescents. This suggests that a
      relatively enduring prototype underlies mothers' attachment style and anchors the
      extent to which mothers experience attachment-related changes following the birth
      of their first child. Within this overall picture of continuity, however, some
      mothers did show change over time, and specific factors emerged as moderators of
      attachment stability, including maternal depressive symptoms and overall
      psychological distress, as well as sensitive care from their own mothers.
      Findings shed light on patterns of continuity and change in new parents'
      development. (PsycINFO Database Record

PMID- 29355360
TI  - New meanings of thin-skinned: The contrasting attentional profiles of typical 12
      month-olds who show high, and low, stress reactivity.
AB  - Previous research is inconsistent as to whether a more labile (faster-changing)
      autonomic system confers performance advantages, or disadvantages, in infants and
      children. To examine this, we presented a stimulus battery consisting of mixed
      static and dynamic viewing materials to a cohort of 63 typical 12-month-old
      infants. While viewing the battery, infants' spontaneous visual attention (looks
      to and away from the screen) was measured. Concurrently, arousal was recorded via
      heart rate (HR), electrodermal activity, head velocity, and peripheral movement
      levels. In addition, stress reactivity was assessed using a mild behavioral
      stressor (watching a video of another infant crying). We found that infants who
      were generally more attentive showed smaller HR increases to the stressor.
      However, they also showed greater phasic autonomic changes to attractive,
      attention-getting stimulus events, a faster rate of change of both look duration
      and of arousal, and more general oscillatory activity in arousal. Finally, 4
      sessions of attention training were applied to a subset of the infants (24
      trained, 24 active controls), which had the effect of increasing visual sustained
      attention. No changes in HR responses to stressor were observed as a result of
      training, but concomitant increases in arousal lability were observed. Our
      results point to 2 contrasting autonomic profiles: infants with high autonomic
      reactivity to stressors show short attention durations, whereas infants with
      lower autonomic reactivity show longer attention durations and greater arousal
      lability. (PsycINFO Database Record

PMID- 29355361
TI  - Is more better? Examining whether enhanced consultation/coaching improves
      implementation.
AB  - It is extremely challenging to implement evidence-based interventions in
      community-based agencies with sufficient quality, fidelity, and intensity to
      produce desired changes in practice and outcomes. This is particularly difficult
      to do within the confines of existing service providers' time, personnel, and
      resource constraints. Over the past 15 years, Together Facing the Challenge
      (TFTC) has been developed, tested, and disseminated in an effort to address this
      set of issues to improve treatment foster care (TFC). Data from the initial
      randomized trial showed improved practice and outcomes in TFTC compared to usual
      TFC. These initial results came from study-led training and follow-up
      consultation. Subsequent dissemination activities suggested potential need for
      more intensive support for TFTC supervisors to produce more consistent and
      sustained implementation of the model. The current randomized trial extends this
      work by comparing the previously tested standard consultation versus enhanced
      consultation that incorporated more of a coaching approach. Initial results
      suggest that enhanced coaching/consultation was associated with improvements in
      the small- to medium-effect size range. Results are promising, but require
      additional work to more fully understand how and whether to enhance supports as
      agencies implement new evidence-based approaches. (PsycINFO Database Record

PMID- 29355362
TI  - Associations of Bullying, Victimization, and Daytime Sleepiness With Academic
      Problems in Adolescents Attending an Alternative High School.
AB  - Adolescents attending alternative high schools often present with high rates of
      academic and behavior problems. They are also at increased risk of poor health
      behaviors and engaging in physical violence compared with students in traditional
      high school settings. To address the needs of students in these educational
      settings, examining factors that influence academic problems in this population
      is essential. Research has established that both bullying/victimization and sleep
      problems increase adolescents' risk for academic problems. Little is known about
      how these 2 factors together may exacerbate risk for academic problems among
      students attending an alternative high school. The current study investigated the
      interaction between teacher-reported bullying, victimization and daytime
      sleepiness on academic concerns (attention and learning problems) among a sample
      of 172 students (56% female; age M = 18.07 years, SD = 1.42) attending an
      alternative high school in a large, Southeastern U.S. city. Findings from path
      models indicated that daytime sleepiness, bullying, and victimization were
      uniquely associated with attention and learning problems. Further, significant
      interactions indicated that the association between victimization/bullying and
      attention/learning problems weakened as levels of daytime sleepiness increased.
      Results suggest the importance of assessing and addressing multiple contextual
      risk factors in adolescents attending alternative high schools to provide
      comprehensive intervention for students in these settings. (PsycINFO Database
      Record

PMID- 29355363
TI  - Medicaid waivers and public sector mental health service penetration rates for
      youth.
AB  - To assist families of youth with serious emotional disturbance in financing
      youth's comprehensive care, some states have sought and received Medicaid
      waivers. Medicaid waivers waive or relax the Medicaid means test for eligibility
      to provide insurance coverage to nonpoor families for expensive, otherwise out-of
      reach treatment for youth with Serious Emotional Disturbance (SED). Waivers
      promote treatment access for the most troubled youth, and the present study
      investigated whether any of several Medicaid waiver options-and those that
      completely omit the means test in particular-are associated with higher state
      wide public sector treatment penetration rates. The investigators obtained data
      from the U.S. Census, SAMHSA's Uniform Reporting System, and the Centers for
      Medicare and Medicaid Services. Analysis employed random intercept and random
      slope linear regression models, controlling for a variety of state demographic
      and fiscal variables, to determine whether a relationship between Medicaid waiver
      policies and state-level public sector penetration rates could be observed.
      Findings indicate that, whether relaxing or completely waiving Medicaid's
      qualifying income limits, waivers increase public sector penetration rates,
      particularly for youth under age 17. However, completely waiving Medicaid income
      limits did not uniquely contribute to penetration rate increases. States offering
      Medicaid waivers that either relax or completely waive Medicaid's means test to
      qualify for health coverage present higher public sector treatment rates for
      youth with behavioral health care needs. There is no evidence that restricting
      the program to waiving the means test for accessing Medicaid would increase
      treatment access. (PsycINFO Database Record

PMID- 29355365
TI  - The importance of positive need fulfillment: Evidence from a sample of war
      affected Sri Lankans.
AB  - There has been growing interest in understanding the psychological and social
      environmental factors that facilitate adaptive functioning in populations
      affected by ethnopolitical warfare. In the current study, we tested the
      hypothesis that a brief measure incorporating local idioms of positive need
      fulfilment would predict functioning in a war-affected Sri Lankan population
      above and beyond psychopathology when controlling for demographic variables and
      current life stressors. A brief measure of positive need fulfillment was derived
      from qualitative data and administered to a sample of 163 Sri Lankans affected by
      the civil war. Positive need fulfillment was found to uniquely predict
      functioning after controlling for age, war-related life problems, and
      psychopathology as assessed by the Penn-RESIST-Peradeniya War Problems
      Questionnaire. These findings highlight the importance of both basic need support
      and the fostering of agency in addition to addressing mental health needs.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29355364
TI  - Anxiety sensitivity and rumination: Transdiagnostic factors involved in the
      relation between subjective social status and anxiety and depressive symptoms and
      disorders among economically disadvantaged Latinos in primary care.
AB  - Latinos face striking physical and mental health disparities. One factor
      associated with such disparities is subjective social status, reflecting
      subjective ratings of social standing. Yet there is presently a lack of empirical
      information about the mechanisms underlying relations between subjective social
      status and anxiety and depressive symptoms and disorders among Latinos in
      community medical services that serve as focal catchment areas for assessment and
      intervention programming. The present investigation examined the unique
      explanatory roles of 2 transdiagnostic factors, rumination and anxiety
      sensitivity, in the relation between subjective social status and depressive,
      suicidal, social anxiety, and anxious arousal symptoms as well as
      anxiety/depressive disorders, among Latinos seeking health services at a primary
      health care facility. Participants included 253 Latino adults with annual incomes
      of less than $30,000 (M age = 39.1, SD = 11.1). Results indicated that rumination
      and anxiety sensitivity each significantly (independently) mediated associations
      between subjective social status and all dependent variables except suicidal
      symptoms. For suicidal symptoms, only rumination was a mediator. The present
      findings suggest that rumination and anxiety sensitivity may represent mechanisms
      for associations between subjective social status and anxiety and depressive
      symptoms and disorders among economically disadvantaged Latinos in primary care
      settings. (PsycINFO Database Record

PMID- 29355366
TI  - Obese and overweight youth: Risk for experiencing bullying victimization and
      internalizing symptoms.
AB  - Obese and overweight youth are at an increased risk for poor peer relations and
      psychosocial adjustment. Of particular concern is the high rate of bullying
      victimization experienced by obese and overweight youth. While it is known that
      victimized youth are at an increased risk for internalizing symptoms, few studies
      have examined if weight status exacerbates the association between victimization
      and internalizing symptoms. The current study drew upon data from over 43,000
      youth attending 107 middle and high schools. Multilevel results suggested that
      compared with normal weight youth, both overweight and obese youth were at an
      increased risk for experiencing relational, verbal, and cyber victimization, with
      only obese youth being at an increased risk for experiencing physical
      victimization. Notably, the odds for experiencing cyber victimization were higher
      than the odds for experiencing other forms of victimization. Frequently
      victimized obese youth, but not frequently victimized overweight youth, had
      significantly higher levels of internalizing symptoms compared to their
      frequently victimized, normal-weight peers. Together, these findings highlight
      the increased risk for psychosocial adjustment problems among frequently
      victimized overweight and obese youth, suggesting these youth may require
      preventive interventions tailored to meet their unique needs. (PsycINFO Database
      Record

PMID- 29355367
TI  - Gendered race modification of the association between chronic stress and
      depression among Black and White U.S. adults.
AB  - Chronic stress stemming from social inequity has long been recognized as a risk
      factor for poor physical and psychological health, yet challenges remain in
      uncovering the mechanisms through which such exposures affect health outcomes and
      lead to racial and gender health disparities. Examination of sociocultural
      influences on group identity, coping, and the expression of stress may yield
      relevant insight into potential pathways of inequity's effect on risk for chronic
      disease. The objective of this study was to examine the relationship between
      chronic stress as measured by allostatic load (AL) and depression by gendered
      race group. Using National Health and Nutrition Examination Survey 2005-2010
      data, we included Black and White U.S. adults aged 18-64 years (n = 6,431). AL
      was calculated using 9 biomarkers; scores >=4 indicated high risk. Depression was
      assessed using the Patient Health Questionnaire-9; scores >=10 indicated likely
      clinical depression. Logistic models estimated odds of depression as a function
      of AL for each gendered race group adjusting for age and family poverty-to-income
      ratio. Effect modification was assessed by analysis of variance and relative
      excess risk due to the interaction. We observed modification on the
      multiplicative scale. High AL was more strongly associated with depression among
      White women and Black men than among Black women or White men. In conclusion, a
      potential manifestation of high chronic stress burden, depression, differs across
      gendered race groups. These disparities may be due to group-specific coping
      strategies that are shaped by unequal social contexts. (PsycINFO Database Record

PMID- 29355369
TI  - Consequences for peers differentially bias computations about risk across
      development.
AB  - Adolescents routinely take risks that impact the well-being of the friends they
      are with. However, it remains unclear when and how consequences for friends
      factor into decisions to take risks. Here we used an economic decision-making
      task to test whether risky choices are guided by the positive and negative
      consequences they promise for peers. Across a large developmental sample of
      participants ages 12-25, we show that risky decision computations increasingly
      assimilate friends' outcomes throughout adolescence into early adulthood in an
      asymmetric manner that overemphasizes protecting friends from incurring loss.
      Whereas adults accommodated friend outcomes to a greater degree when the friend
      was present and witnessing these choices, adolescents did so regardless of
      whether a friend could witness their decisions, highlighting the fundamentality
      of adolescent social motivations. By demonstrating that outcomes for another
      individual can powerfully tune an actor's risk tolerance, these results identify
      a key factor underlying peer-related motivations for risky behavior, with
      implications for the law and risk-prevention. (PsycINFO Database Record

PMID- 29355370
TI  - Perceptual but not complex moral judgments can be biased by exploiting the
      dynamics of eye-gaze.
AB  - Can judgments be biased via passive monitoring of eye-gaze? We examined this
      question using a perceptual discrimination task (Experiment 1) and a complex
      moral judgment task (Experiment 2). Information about the location of
      participants' gaze at particular time-points in a trial was used to prompt
      responses. When there was no objective perceptual information available to
      decision-makers, the timing of the prompt had a small, but detectable effect on
      judgments (Experiment 1). However, this small effect did not scale up to more
      complex judgments about moral issues (Experiment 2). Our results are consistent
      with the well-established idea that participants' judgments are reflected in
      their eye-gaze, but do not support the recent bold claim of a causal link wherein
      the timing of a gaze-contingent response-prompt influences complex judgments.
      (PsycINFO Database Record

PMID- 29355368
TI  - Profiles of minority stressors and identity centrality among sexual minority
      Latinx youth.
AB  - Few studies have examined how the amalgamation of minority stressors for youth
      with multiple marginalized identities is associated with well-being.
      Additionally, among youth with multiple marginalized identities, identity
      centrality may clarify the associations between specific types of minority
      stressors (i.e., bias-based peer victimization, perceived discrimination) and
      adjustment. This study sought to identify intersectional profiles of perceived
      peer victimization, perceived discrimination, and identity centrality, specific
      to either Latinx ethnicity or sexual minority identity in the United States.
      Demographic characteristics associated with each profile (i.e., age,
      socioeconomic status, gender nonconformity, survey language, gender, rurality)
      were examined, as well as associations between profiles and grade point average,
      self-esteem, and depression. In a sample of 219 in-school Latinx sexual minority
      youth (47% secondary, 53% postsecondary; Mage = 19 years, SD = 2.3), four
      profiles of intersectional minority stress (perceived victimization,
      discrimination) and identity centrality were identified: (a) low stress, low
      centrality; (b) low stress, high centrality; (c) moderate stress, moderate
      centrality, and (d) high stress, moderate centrality. Men, youth who were
      relatively older, socioeconomically advantaged, gender nonconforming, and those
      living in urban areas had higher probabilities of membership in profiles with
      moderate and high stress. Compared to the low stress, low centrality profile,
      profiles with higher levels of intersectional stress were associated with
      maladjustment, whereas the profile characterized by low stress, high centrality
      had higher levels of self-esteem. (PsycINFO Database Record

PMID- 29355371
TI  - The awakening of the attention: Evidence for a link between the monitoring of
      mind wandering and prospective goals.
AB  - Across 2 independent samples, we examined the relation between individual
      differences in rates of self-caught mind wandering and individual differences in
      temporal monitoring of an unrelated response goal. Rates of self-caught mind
      wandering were assessed during a commonly used sustained-attention task, and
      temporal goal monitoring was indexed during a well-established prospective-memory
      task. The results from both samples showed a positive relation between rates of
      self-caught mind wandering during the sustained-attention task and rates of
      checking a clock to monitor the amount of time remaining before a response was
      required in the prospective-memory task. This relation held even when controlling
      for overall propensity to mind-wander (indexed by intermittent thought probes)
      and levels of motivation (indexed by subjective reports). These results suggest
      the possibility that there is a common monitoring system that monitors the
      contents of consciousness and the progress of ongoing goals and tasks. (PsycINFO
      Database Record

PMID- 29355372
TI  - M(4) muscarinic receptors and locomotor activity regulation.
AB  - M(4) muscarinic receptors (M(4) MR) represent a subfamily of G-protein coupled
      receptors serving a substantial role in spontaneous locomotor activity
      regulation, cognition and modulation of cholinergic system. With increasing body
      of literature discussing the role of M(4) MR some controversies arose. Thus, we
      try here to summarize the current evidence regarding the M(4) MR, with the
      special focus on their role in Locomotor activity control. We review the
      molecular function of M(4) MR in specific brain areas implicated in locomotor
      regulation, and shortly in other CNS processes that could be connected to
      locomotor activity. We also focus on brain areas implicated in locomotor activity
      biorhythm changes like suprachiasmatic nucleus, subparaventricular zone posterior
      hypothalamic area, striatum and thalamus. Gender-related aspects and differences
      in locomotor activity in males and females are discussed further.

PMID- 29355373
TI  - Does prenatal methamphetamine exposure induce sensitization to drugs in
      adulthood?
AB  - Behavioral sensitization is defined as augmented psychomotor activity, which can
      be observed after drug re-administration following withdrawal of repeated drug
      exposure. It has been shown that abuse of one drug can lead to increased
      sensitivity to certain other drugs. This effect of developed general drug
      sensitivity is called cross-sensitization and has been reported between drugs
      with similar as well as different mechanisms of action. There is growing evidence
      that exposure to drugs in utero not only causes birth defects and delays in
      infant development, but also impairs the neural reward pathways, in the brains of
      developing offspring, in such a way that it can increase the tendency for drug
      addiction later in life. This review summarizes the results of preclinical
      studies that focused on testing behavioral cross-sensitization, after prenatal
      Methamphetamine exposure, to drugs administered in adulthood, with both similar
      and different mechanisms of action. Traditionally, behavioral sensitization has
      been examined using the Open field or the Laboras Test to record locomotor
      activity, and the Conditioned Place Preference and Self-administration test to
      examine drug-seeking behavior. However, it seems that prenatal drug exposure can
      sensitize animals not only to the locomotor-stimulating and conditioning effects
      of drugs, but may also be responsible for modified responses to various drug
      effects.

PMID- 29355374
TI  - Olfactory bulbectomy in methamphetamine-treated rat mothers induces impairment in
      somatic and functional development of their offspring.
AB  - Olfactory bulbectomy in rodents is considered a putative model of depression.
      Depression is often associated with drug addiction. Our previous studies
      demonstrated that methamphetamine (MA) administration to rat mothers affects
      both, mothers and their pups. The aim of the present study was to examine the
      effect of bulbectomy, as a model of depression, and MA administration on behavior
      of rat mothers and postnatal development of their pups. Adult female Wistar rats
      were randomly divided into two groups: bulbectomized (OBX) and sham-operated
      (SH). A period of 20 days was allowed for the development of the depressive-like
      phenotype. Animals were tested in the motor activity test and 2 % sucrose
      preference for anhedonia and hyperactive locomotor response to a novel
      environment, respectively. After then females were impregnated. Pregnant females
      were exposed to daily subcutaneous (s.c.) injection of MA (5 mg/kg) or saline
      (SA) during the entire gestation period. Postnatally, maternal behavior and pup
      development was examined. The effect of a challenge dose of MA (1 mg/kg, s.c.) on
      behavior was further examined in adult male offspring. Our results showed no
      differences in the maternal behavior as a matter of bulbectomy, only OBX rats
      slept more than all the SH controls. Pups from OBX mothers were born with lower
      birthweight and gained less weight during the postnatal development than pups
      from SH controls. Both, bulbectomy and MA administration, delayed the eyes
      opening. As a matter of functional development of the pups, maternal OBX
      procedure impaired the performance in the Bar-holding test, but only in saline
      group. OBX/SA group was the worst in the Bar-holding test relative to all the
      other groups. In addition, pups from OBX mothers dropped more boluses during the
      Bar-holding test, suggesting that they were more stressed. In adult male
      offspring, bulbectomy increased immobility only in the SA/SA group. Prenatal MA
      exposure increased locomotion, while decreasing immobility. In addition,
      challenge dose of MA in adulthood increased distance traveled, locomotion,
      rearing, and average and maximal velocity, while decreasing immobility and
      grooming. In conclusion, our results suggest that depressive-like phenotype of
      rat mothers induces impairment in somatic and functional development of their
      male offspring.

PMID- 29355375
TI  - Effects of perinatal stress and drug abuse on maternal behavior and sensorimotor
      development of affected progeny.
AB  - Methamphetamine (MA) is an addictive psychostimulant with significant potential
      for abuse. Previous rat studies have demonstrated that MA use during pregnancy
      impairs maternal behavior and induced delayed development of affected pups. The
      offspring of drug-addictive mothers were often neglected and exposed to neonatal
      stressors. The present study therefore examines the effect of perinatal stressors
      combined with exposure to prenatal MA on the development of pups and maternal
      behavior. Dams were divided into three groups according to drug treatment during
      pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg).
      Litters were divided into four groups according to postnatal stressors: controls
      (N); maternal separation (S); maternal cold-water stress (W); maternal separation
      plus cold-water stress (SW). The pup-retrieval test showed differences among
      postnatally stressed mothers and non-stressed controls. The righting reflex on a
      surface revealed delayed development of pups prenatally exposed to MA/SA and
      postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA
      group was the most affected. Overall, our data suggests that a combination of
      perinatal stress and prenatal MA can have a detrimental effect on maternal
      behavior as well as on the sensorimotor development of pups. However, MA exposure
      during pregnancy seems to be the decisive factor for impairment.

PMID- 29355376
TI  - Do multiple body modifications alter pain threshold?
AB  - In recent years, epidemiological data has shown an increasing number of young
      people who deliberately self-injure. There have also been parallel increases in
      the number of people with tattoos and those who voluntarily undergo painful
      procedures associated with piercing, scarification, and tattooing. People with
      self-injury behaviors often say that they do not feel the pain. However, there is
      no information regarding pain perception in those that visit tattoo parlors and
      piercing studios compared to those who don't. The aim of this study was to
      compare nociceptive sensitivity in four groups of subjects (n=105, mean age 26
      years, 48 women and 57 men) with different motivations to experience pain (i.e.,
      with and without multiple body modifications) in two different situations; (1) in
      controlled, emotionally neutral conditions, and (2) at a "Hell Party" (HP), an
      event organized by a piercing and tattoo parlor, with a main event featuring a
      public demonstration of painful techniques (burn scars, hanging on hooks, etc.).
      Pain thresholds of the fingers of the hand were measured using a thermal
      stimulator and mechanical algometer. In HP participants, information about
      alcohol intake, self-harming behavior, and psychiatric history were used in the
      analysis as intervening variables. Individuals with body modifications as well as
      without body modifications had higher thermal pain thresholds at Hell Party,
      compared to thresholds measured at control neutral conditions. No such
      differences were found relative to mechanical pain thresholds. Increased pain
      threshold in all HP participants, irrespectively of body modification, cannot be
      simply explained by a decrease in the sensory component of pain; instead, we
      found that the environment significantly influenced the cognitive and affective
      component of pain.

PMID- 29355377
TI  - Prefrontal cortex and dorsomedial hypothalamus mediate food reward-induced
      effects via npas2 and egr1 expression in rat.
AB  - The effects of food reward on circadian system function were investigated in the
      hypothalamic nuclei, prefrontal cortex and liver. Food rewards of small hedonic
      and caloric value were provided for 16 days 3 h after light phase onset to male
      Wistar rats. The daily pattern of locomotor activity was monitored. Gene
      expression profiling performed in the dorsomedial hypothalamus (DMH) and liver at
      the time of reward delivery indicated transcriptional factors egr1 and npas2 as
      possible mediators of food reward effects. Candidate genes were measured in the
      suprachiasmatic nuclei (SCN), DMH, arcuate nucleus (ARC), prefrontal cortex (PFC)
      and liver along with per2 expression. A daily pattern in glycemia and per2
      expression in the SCN was emphasized by food reward. The expression of egr1 was
      rhythmic in the SCN, DMH, PFC and liver and food reward weakened or diminished
      this rhythm. The expression of npas2 was rhythmic in all tissues except for the
      PFC where food reward induced rhythm in npas2 expression. Food reward induced
      npas2 and egr1 expression in the DMH at the time of reward delivery. We suppose
      that the DMH and PFC participate in the adjustment of the circadian system to
      utilize food reward-induced input via egr1 and npas2 expression.

PMID- 29355378
TI  - Methylprednisolone modulates intracranial pressure in the brain cellular edema
      induced by water intoxication.
AB  - Continuous monitoring of the intracranial pressure (ICP) detects impending
      intracranial hypertension resulting from the impaired intracranial volume
      homeostasis, when expanding volume generates pressure increase. In this study,
      cellular brain edema (CE) was induced in rats by water intoxication (WI).
      Methylprednisolone (MP) was administered intraperitoneally (i.p.) before the
      start of CE induction, during the induction and after the induction. ICP was
      monitored for 60 min within 20 h after the completion of the CE induction by
      fibreoptic pressure transmitter. In rats with induced CE, ICP was increased
      (Mean+/-SEM: 14.25+/-2.12) as well as in rats with MP administration before the
      start of CE induction (10.55+/-1.27). In control rats without CE induction
      (4.62+/-0.24) as well as in rats with MP applied during CE induction (5.52+/
      1.32) and in rats with MP applied after the end of CE induction (6.23+/-0.73) ICP
      was normal. In the last two groups of rats, though the CE was induced,
      intracranial volume homeostasis was not impaired, intracranial volume as well as
      ICP were not increased. It is possible to conclude that methylprednisolone
      significantly influenced intracranial homeostasis and thus also the ICP values in
      the model of cellular brain edema.

PMID- 29355379
TI  - Fecal calprotectin levels correlate with main domains of the autism diagnostic
      interview-revised (ADI-R) in a sample of individuals with autism spectrum
      disorders from Slovakia.
AB  - Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by
      impaired social interaction and communication, as well as repetitive behavior and
      restricted interests. There is convincing evidence that the intestinal
      inflammation is involved in etiology of ASD. Increased levels of inflammatory
      markers were shown to be associated with more aberrant behaviors and
      communication of subjects with ASD. Calprotectin in the feces is produced by
      activated neutrophils and epithelial cells of the gut mucosa, and its levels
      reflect local inflammation of the gastrointestinal tract. Concentration of fecal
      calprotectin was determined by ELISA method in 87 individuals with ASD and 51
      controls, of that 29 siblings of children with ASD and 22 non-related controls.
      In non-relatives significantly lower values of fecal calprotectin were observed
      than in both subjects with ASD and their siblings. In the group with ASD
      significant correlations of fecal calprotectin with all domains of the ADI-R
      diagnostic tool were found: qualitative abnormalities in reciprocal social
      interaction and communication, restrictive and repetitive patterns of behavior.
      Results suggest that low grade intestinal inflammation may be one of factors
      implicated in the pathophysiology of ASD.

PMID- 29355380
TI  - Electrocardiographic outcome of resynchronization therapy.
AB  - Cardiac resynchronization therapy (CRT) has proven efficacious in reducing or
      even eliminating cardiac dyssynchrony and thus improving heart failure symptoms.
      However, quantification of mechanical dyssynchrony is still difficult and
      identification of CRT candidates is currently based just on the morphology and
      width of the QRS complex. As standard 12-lead ECG brings only limited information
      about the pattern of ventricular activation, we aimed to study changes produced
      by different pacing modes on the body surface potential maps (BSPM). Total of 12
      CRT recipients with symptomatic heart failure (NYHA II-IV), sinus rhythm and QRS
      width >/=120 ms and 12 healthy controls were studied. Mapping system Biosemi (123
      unipolar electrodes) was used for BSPM acquisition. Maximum QRS duration, longest
      and shortest activation times (ATmax and ATmin) and dispersion of QT interval
      (QTd) were measured and/or calculated during spontaneous rhythm, single-site
      right- and left-ventricular pacing and biventricular pacing with ECHO-optimized
      AV delay. Moreover we studied the impact of CRT on the locations of the early and
      late activated regions of the heart. The average values during the spontaneous
      rhythm in the group of patients with dyssynchrony (QRS 140.5+/-10.6 ms, ATmax
      128.1+/-10.1 ms, ATmin 31.8+/-6.7 ms and QTd 104.3+/-24.7 ms) significantly
      differed from those measured in the control group (QRS 93.0+/-10.0 ms, ATmax
      79.1+/-3.2 ms, ATmin 24.4+/-1.6 ms and QTd 43.6+/-10.7 ms). Right ventricular
      pacing (RVP) improved significantly only ATmax [111.2+/-10.6 ms (p<0.05)] but no
      other measured parameters. Left ventricular pacing (LVP) succeeded in improvement
      of all parameters [QRS 105.1+/-8.0 ms (p<0.01), ATmax 103.7+/-7.1 ms (p<0.01),
      ATmin 20.2+/-3.7 ms (p<0.01) and QTd 52.0+/-9.4 ms (p<0.01)]. Biventricular
      pacing (BVP) showed also a beneficial effect in all parameters [QRS 121.3+/-8.9
      ms (p<0.05), ATmax 114.3+/-8.2 ms (p<0.05), ATmin 22.0+/-4.1 ms (p<0.01) and QTd
      49.8+/-10.0 ms (p<0.01)]. Our results proved beneficial outcome of LVP and BVP in
      evaluated parameters (what seems to be important particularly in the case of
      activation times) and revealed a complete return of activation times to normal
      distribution when using these CRT modalities.

PMID- 29355381
TI  - Detection of microembolic signals in the common carotid artery using Doppler
      sonography in the porcine model of acute heart failure treated by veno-arterial
      extracorporeal membrane oxygenation.
AB  - Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a method used for
      the treatment most severe cases of decompensated heart failure. The purpose of
      this study was to evaluate the risk of the formation of microembolisms during VA
      ECMO-based therapy. Heart failure was induced with simultaneous detection of
      microembolisms and the measurement of blood flow rate in the common carotid
      artery (CCA) without VA-ECMO (0 l/min) and at the VA-ECMO blood flow rate of 1,
      2, 3 and 4 l/min. If embolisms for VA-ECMO 0 l/min and the individual regimes for
      VA-ECMO 1, 2, 3, 4 l/min are compared, a higher VA-ECMO flow rate is accompanied
      by a higher number of microembolisms. The final microembolism value at 16 min was
      for the VA-ECMO flow rate of 0 l/min 0.0 (0, 1), VA-ECMO l/min 7.5 (4, 19), VA
      ECMO 2 l/min 12.5 (4, 26), VA-ECMO 3 l/min, 21.0 (18, 57) and VA-ECMO 4 l/min,
      27.5 (21, 64). Such a comparison is statistically significant if VA-ECMO 0 vs. 4
      l/min p<0.0001, 0 vs. 3 l/min p<0.01 and 1 vs. 4 l/min p<0.01 are compared. The
      results confirm that high VA-ECMO flow rates pose a risk with regards to the
      formation of a significantly higher number of microemboli in the blood
      circulation and that an increase in blood flow rates in the CCA corresponds to
      changes in the VA-ECMO flow rates.

PMID- 29355382
TI  - Effect of perivascular adipose tissue on arterial adrenergic contractions in
      normotensive and hypertensive rats with high fructose intake.
AB  - The aim of this study was to investigate the effect of high fructose intake
      associated with moderate increase in adiposity on rat arterial adrenergic
      responses and their modulation by perivascular adipose tissue (PVAT). After eight
      week-lasting substitution of drinking water with 10 % fructose solution in adult
      normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR),
      their systolic blood pressure, plasma triglycerides, and relative liver weight
      were elevated when compared to their respective control groups. Moreover, in SHR,
      body weight and relative heart weight were increased after treatment with
      fructose. In superior mesenteric arteries, PVAT exerted inhibitory influence on
      adrenergic contractile responses and this effect was markedly stronger in control
      WKY than in SHR. In fructose-administered WKY, arterial adrenergic contractions
      were substantially reduced in comparison with the control group; this was caused
      mainly by enhancement of anticontractile action of PVAT. The diminution of the
      mesenteric arterial contractions was not observed after fructose treatment in
      SHR. We conclude that the increase in body adiposity due to fructose overfeeding
      in rats might have prehypertensive effect. However, in WKY it might cause PVAT
      dependent and independent reduction in arterial contractile responses to
      adrenergic stimuli, which could attenuate the pathological elevation in vascular
      tone.

PMID- 29355383
TI  - Changes of cortical perfusion in the early phase of subarachnoid bleeding in a
      rat model and the role of intracranial hypertension.
AB  - Brain perfusion is reduced early after subarachnoid hemorrhage (SAH) due to
      intracranial hypertension and early vasospasm. The contribution of these two
      mechanisms is unknown. By performing a prophylactic decompressive craniectomy
      (DC) in a rat model of SAH we aimed to study brain perfusion after the component
      of intracranial hypertension has been eliminated. We used 2x2 factorial design,
      where rats received either decompressive craniectomy or sham operation followed
      by injection of 250 microl of blood or normal saline into prechiasmatic cistern.
      The cortical perfusion has been continually measured by laser speckle-contrast
      analysis for 30 min. Injection of blood caused a sudden increase of intracranial
      pressure (ICP) and drop of cerebral perfusion, which returned to baseline within
      6 min. DC effectively prevented the rise of ICP, but brain perfusion after SAH
      was significantly lower and took longer to normalize compared to non-DC animals
      due to increased cerebral vascular resistance, which lasted throughout 30 min
      experimental period. Our findings suggest that intracranial hypertension plays
      dominant role in the very early hypoperfusion after SAH whilst the role of early
      vasospasm is only minor. Prophylactic DC effectively maintained cerebral
      perfusion pressure, but worsened cerebral perfusion by increased vascular
      resistance.

PMID- 29355384
TI  - Non-invasive assessment of vascular system function and damage induced by
      anthracycline treatment in the pediatric cancer survivors.
AB  - Anthracyclines represent one of the important classes of anti-cancer drugs;
      however, their major disadvantage is their profound cardiovascular toxicity. This
      study aimed to evaluate influence of anthracyclines on cardiovascular stiffness
      parameters estimated from pulse wave (PW). PW was measured in 59 cancer survivors
      treated with anthracyclines in childhood and in 248 healthy age-matched controls.
      Both patients and controls were divided into three age groups (13 - 15, 16 - 18
      and 19 - 24 years). Central PW augmentation index (C-AI75) and augmentation
      pressure (C-AP75), both normalized to heart rate 75 bpm, were calculated as
      parameters of arterial wall stiffness. Central Buckberg sub-endocardial viability
      ratio (SEVR) was calculated as a parameter of diastolic function. Patients and
      controls were compared in each age group. C-AI75 and C-AP75 were significantly
      increased in patients in age groups 16 - 18 and 19 - 24 years. SEVR was decreased
      in patients in the oldest age group. Our results suggest that although toxic
      influence of anthracyclines to arterial wall and heart are developing during
      childhood and puberty, they can be detected rather in the adulthood. These
      changes are yet subclinical; however, their presence indicates potentially
      increased cardiovascular risk in childhood cancer survivors treated with
      anthracyclines during childhood.

PMID- 29355386
TI  - Effect of essential oils on enzymatic activities in the intestinal apparatus and
      growth ability of laboratory mice.
AB  - The influence of essential oils (EOs) from medicinal and aromatic plants from
      sage (SA), cinnamon (CN), thyme (TH) and oregano (OR) on the amylolytic,
      proteolytic and cellulolytic activities in chyme of the duodenum (DU), the small
      (SI) and large intestine (LI), the caecum (CE) and the rectum (RE) as well as on
      the growth ability of laboratory ICR outbred mice were compared in four feeding
      trials. The negative control was present in the each trial. EOs were mixed into a
      feed mixture (crude protein (CP) 170.0, fibre 115.0, fat 27.0, lysine 7.0,
      methionine and cysteine 6.7, Ca 9.0, P 6.0 g.kg(-1) dry matter (DM), metabolic
      energy (ME) 10 MJ.kg(-1) DM) of experimental group as follows: 1) 6 groups (n=36,
      age 63 days, period 14 days) SA, CN, TH, OR, the blend of SA with OR, the dosages
      of EOs 0.42 except OR 0.21 ml.100 g(-1) feed, 2) 2 groups (n=12, age 28 days,
      period 30 days) blend of SA 0.42 with OR 0.21 ml.100 g(-1) feed, 3) 3 groups
      (n=18, age 28 days, period 58 days) CN and TH, both 0.5 ml.100 g(-1) feed, 4) 2
      groups (n=12, age 28 days, period 8 days) the blend of CN with TH 0.42 ml.100 g(
      1) feed. The peroral intake of blend of EOs from OR with SA increased the weight
      gains by 25 %. Additionally, it stimulated the activities of digestive enzymes in
      the chyme of intestinal apparatus of laboratory mice in the experimental group
      compared to control as follows: amylolytic by 4,138 micromol.s(-1).g(-1) and
      proteolytic by 282.2 mg azoalbumin.min(-1).g(-1) in SI (p<0.01), cellulolytic by
      23.58 in LI and by 34.87 mmol glucose.min(-1).g(-1) in CE (p<0.01).

PMID- 29355385
TI  - Nitric oxide elevation in polytrauma is driven by oxygen radicals.
AB  - A common problem in management of polytrauma - a simultaneous injury to more than
      one organ or organ system, at least one of them lethal without intervention - is
      a discrepancy between a relatively good initial state and a serious subsequent
      development. Since nitric oxide (NO) is produced in high quantities during tissue
      injury, we assumed that serum levels of NO (and its oxidation products, NOx)
      might serve as a prognostic marker of polytrauma severity. However, we found
      recently that NOx was increased in polytrauma, but not in the most severe cases.
      The present study was undertaken to test the hypothesis that serum NOx is reduced
      in severe polytrauma by concomitant overproduction of reactive oxygen species
      (ROS). Polytrauma was induced in rats under anesthesia by bilateral fracture of
      femurs and tibiae plus incision of the right liver lobe through laparotomy. Serum
      NOx was measured by chemiluminescence after hot acidic reduction. The role of ROS
      was assessed by treatment with an antioxidant, N-acetyl-L-cysteine (NAC).
      Experimental polytrauma elevated NOx from 11.0+/-0.7 to 23.8+/-4.5 ppb. This was
      completely prevented by NAC treatment (9.1+/-2.2 ppb). Serum NOx is elevated in
      severe polytrauma, and this is not reduced by ROS. On the contrary, ROS are
      necessary for the NOx elevation, probably because ROS produced by inflammatory
      cells activated by the polytrauma induce massive NO production.

PMID- 29355387
TI  - Gender-dependent expression of leading and passenger strand of miR-21 and miR-16
      in human colorectal cancer and adjacent colonic tissues.
AB  - miRNAs are small regulatory RNA molecules involved in posttranscriptional gene
      silencing. Their biosynthesis results in the formation of duplex consisting of a
      leading and a passenger strand of mature miRNA. The leading strand exhibits the
      main activity but recent findings indicate a certain role of the passenger strand
      as well. Deregulated levels of miRNA were found in many types of cancers
      including colorectal cancer. miR-21 and miR-16 were indicated as possible markers
      of colorectal cancer, however, small attention to gender differences in their
      expression was paid so far. Therefore, the aim of our study was to investigate
      the expression of miR-21-5p, miR-21-3p, miR-16-5p and miR-16-3p in human
      colorectal cancer tissue and compare it to the adjacent tissues taken during
      surgery in men and women separately. Our results showed an up-regulation of all
      measured miRNAs in tumor tissue compared to adjacent tissues. As expected, tumors
      and adjacent tissues exhibited a significantly higher expression of leading
      miRNAs compared to passenger strand of miR-21 and miR-16. The expression of
      leading and passenger strand of miR-21 and miR-16 positively correlated
      exhibiting the highest correlation coefficient in the distal tissue. The
      expression pattern showed gender-dependent differences, with higher levels of
      miRNA in men than in women. Our findings indicate a gender-related expression
      pattern of miRNA, which should be considered as an important factor in generating
      new prognostic or diagnostic biomarkers.

PMID- 29355388
TI  - Muscle structure and gene expression in pectoralis major muscle in response to
      deep pectoral myopathy induction in fast- and slow-growing commercial broilers.
AB  - 1. The objective of this study was to determine muscle structure and gene
      expression in pectoralis major (p. major) muscle of broilers in response to deep
      pectoral myopathy (DPM) induction. 2. A total of 160 chickens from slow- and fast
      growing broilers were raised under same conditions. Half of the broilers from
      each strain were encouraged to wing flap when they reached 2800 g body weight.
      Pectoralis minor (p. minor) muscle of the broilers was inspected for the
      occurrence of DPM and p. major samples were collected from broilers with or
      without DPM. The muscle fibre area and number, capillary number and the
      signalling pathways of vascular development (vascular endothelial growth factor
      A, VEGFA) and muscle contraction regulation (actin alpha 1, ACTA1; myosin light
      chain kinase 2, MYLK2 and ATPase Ca+2 transporting gene 1, ATP2A1) were studied
      in p. major muscle. 3. DPM induction increased fibre area of p. major muscle with
      a greater rate in the slow-growing strain compared with fast-growing line.
      Although the capillary number was higher in slow-growing compared with fast
      growing broilers, in the case of DPM induction, the number of capillaries was
      similar between strains. 4. Expression of VEGFA, MYLK2 and ATP2A1 was greater in
      slow- than in fast-growing broilers. DPM induction increased expression of ACTA1,
      VEGFA and ATP2A1 in p. major muscle of broilers from both strains; however, MYLK2
      expression was downregulated. 5. Changes in capillary density and expression of
      VEGFA found in the p. major muscle of broilers with DPM suggest increased blood
      flow to increase oxygen availability. The upregulation of ATP2A1 by DPM induction
      could be attributable to alterations in calcium ion transportation from the
      cytoplasm into the sarcoplasmic reticulum. 6. The results are evidence of changes
      in muscle structure and gene expression pathways in p. major muscle of broilers
      with DPM.

PMID- 29355389
TI  - Attentional dysfunction and recovery in concussion: effects on the P300m and
      contingent magnetic variation.
AB  - PRIMARY OBJECTIVE: To examine the effect of concussion on indices of attention
      using magnetoencephalography. METHODS AND PROCEDURES: Thirteen patients were
      recruited from the emergency department and scanned within 3-6 days of injury.
      Five returned for follow-up scans one and three months post-injury. Thirteen
      healthy controls also completed testing. During MEG acquisition, participants
      performed the Attention Network Test (ANT). Cognitive evoked responses to this
      task include a cue-evoked P300m, a contingent magnetic variation (CMV) and a
      target-evoked P300m. The Rivermead Postconcussion Symptom Questionnaire and Sport
      Concussion Assessment Tool (SCAT3) were administered in all sessions. RESULTS:
      Patients suffering from concussion had slower response times and benefitted more
      from spatial cues than did controls. Global activation for all three evoked
      responses was lower for patients than controls. In a small sample of patients who
      returned for follow-up, the CMV and target P300m improved with recovery.
      CONCLUSIONS: MEG-evoked responses to the ANT reveal neurophysiological evidence
      of attentional dysfunction within days of injury. A pattern of improvement was
      also observed over the course of three months for the P300m, while behavioural
      performance did not change significantly. Further development of this method may
      yield a useful adjunct to neurological examination for concussion diagnosis and
      monitoring.

PMID- 29355390
TI  - The International Communication Project: Raising global awareness of
      communication as a human right.
AB  - Communication as a human right is embedded within Article 19 of the Universal
      Declaration of Human Rights; however, there is a need to raise global awareness
      of the communication needs of those with communication disorders. In 2014, the
      six national speech-language and audiology professional bodies that comprise the
      Mutual Recognition Agreement (MRA) launched the International Communication
      Project (ICP) to help raise awareness of communication disorders around the
      world. Since its inception, the project has engaged close to 50 organisations
      from diverse regions, and has undertaken a number of initiatives, including
      development of the Universal Declaration of Communication Rights. A consultancy
      report was commissioned to inform ICP efforts to influence international policy
      bodies. As a result, the current focus of the ICP is to identify opportunities to
      influence the policies of organisations such as the World Health Organization,
      the United Nations and World Bank to more explicitly acknowledge and address
      communication as a human right. This commentary paper describes the work of the
      ICP to date, with an emphasis on the place of communication disorders in current
      international policy and potential pathways for advocacy.

PMID- 29355391
TI  - Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for
      Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of
      American Pathologists, the International Association for the Study of Lung
      Cancer, and the Association for Molecular Pathology.
AB  - CONTEXT: - In 2013, an evidence-based guideline was published by the College of
      American Pathologists, the International Association for the Study of Lung
      Cancer, and the Association for Molecular Pathology to set standards for the
      molecular analysis of lung cancers to guide treatment decisions with targeted
      inhibitors. New evidence has prompted an evaluation of additional laboratory
      technologies, targetable genes, patient populations, and tumor types for testing.
      OBJECTIVE: - To systematically review and update the 2013 guideline to affirm its
      validity; to assess the evidence of new genetic discoveries, technologies, and
      therapies; and to issue an evidence-based update. DESIGN: - The College of
      American Pathologists, the International Association for the Study of Lung
      Cancer, and the Association for Molecular Pathology convened an expert panel to
      develop an evidence-based guideline to help define the key questions and
      literature search terms, review abstracts and full articles, and draft
      recommendations. RESULTS: - Eighteen new recommendations were drafted. The panel
      also updated 3 recommendations from the 2013 guideline. CONCLUSIONS: - The 2013
      guideline was largely reaffirmed with updated recommendations to allow testing of
      cytology samples, require improved assay sensitivity, and recommend against the
      use of immunohistochemistry for EGFR testing. Key new recommendations include
      ROS1 testing for all adenocarcinoma patients; the inclusion of additional genes (
      ERBB2, MET, BRAF, KRAS, and RET) for laboratories that perform next-generation
      sequencing panels; immunohistochemistry as an alternative to fluorescence in situ
      hybridization for ALK and/or ROS1 testing; use of 5% sensitivity assays for EGFR
      T790M mutations in patients with secondary resistance to EGFR inhibitors; and the
      use of cell-free DNA to "rule in" targetable mutations when tissue is limited or
      hard to obtain.

PMID- 29355392
TI  - Factor structure of the Rivermead Post-Concussion Symptoms Questionnaire over the
      first year following mild traumatic brain injury.
AB  - BACKGROUND: We examined the factor structure of the Rivermead Post-Concussion
      Symptom Questionnaire (RPQ), the most commonly used measure of post-concussive
      symptoms, over the first year post-injury. METHOD: Factor analysis (orthogonal
      rotation) was used to examine the RPQ items that form coherent subsets/factors
      within 2-weeks, and 1, 6, and 12-months post-mTBI in 527 adults (age >16 years).
      RESULTS: At baseline, three factors accounted for 63.95% of the variance; factor
      1 reflected cognitive and physiological disturbances; factor 2 included items
      reflecting mood, sleep, and nausea/vomiting; and factor 3 included
      visual/auditory disturbances, dizziness, and headaches. At 1 month, three factors
      were again extracted (63.26% variance). Factor 1 reflected cognitive and mood
      symptoms, factor 2 reflected mood with headache, nausea, and dizziness; and
      factor 3 reflected visual disturbances. Two factors were obtained at 6 and 12
      months (63.7% and 63.38% of variance): factor 1 included mood/cognitive items,
      restlessness, sleep disturbance, and noise sensitivity; whereas, factor 2
      included physiological symptoms. CONCLUSIONS: The factor structure of the RPQ
      changes over time; however, it was relatively stable from 6 to 12-months post
      injury. Subject to further evaluation, assessments conducted from 6 months could
      consider using these two factors as subscales. Changing the factor structure of
      RPQ before 6 months suggests that timing of assessment should be considered in
      applying these factors.

PMID- 29355394
TI  - The Investigation of the Cox-2 Selective Inhibitor Parecoxib Effects in Spinal
      Cord Injury in Rat.
AB  - AIM: Today, spinal cord injury (SCI) can be rehabilitated but cannot be treated
      adequately. This experimental study was conducted to investigate possible
      beneficial effects of methylprednisolone and parecoxib in treatment of SCI.
      MATERIALS AND METHODS: Forty-eight male Wistar albino rats were assigned into
      CONTROL, acute (MP-A, PX-A, and PXMP-A), and subacute (MP-S, PX-S, and PXMP-S)
      stage groups. Then, to induce SCI, a temporary aneurysm clip was applied to the
      spinal cord following T7-8 laminectomy, except in the CONTROL group. Four hours
      later parecoxib, methylprednisolone, or their combination was administered to
      rats intraperitoneally except CONTROL, SHAM-A, and SHAM-S groups. Rats in the
      acute stage group were sacrificed 72 h later, and whereas rats in the subacute
      stage were sacrificed 7 days later for histopathological and biochemical
      investigation and for gene-expression analyses. RESULTS: Parecoxib and
      methylprednisolone and their combination could not improve histopathological
      grades in any stage. They also could not decrease malondialdehyde or caspase-3,
      myeloperoxidase levels in any stage. Parecoxib and methylprednisolone could
      decrease the TNF-alpha gene expression in subacute stage. Methylprednisolone
      could increase TGF-1beta gene-expression level in acute stage. CONCLUSION:
      Neither of the experimental drugs, either alone or in combination, did not show
      any beneficial effects in SCI model in rats.

PMID- 29355393
TI  - Burden and Management of Noncommunicable Diseases After Earthquakes and Tsunamis.
AB  - This integrative review examines extant literature assessing the burden and
      management of noncommunicable diseases 6 months or more after earthquakes and
      tsunamis. We conducted an integrative review to identify and characterize the
      strength of published studies about noncommunicable disease-specific outcomes and
      interventions at least 6 months after an earthquake and/or tsunami. We included
      disasters that occurred from 2004 to 2016. We focused primarily on the World
      Health Organization noncommunicable disease designations to define chronic
      disease, but we also included chronic renal disease, risk factors for
      noncommunicable diseases, and other chronic diseases or symptoms. After removing
      duplicates, our search yielded 6,188 articles. Twenty-five articles met our
      inclusion criteria, some discussing multiple noncommunicable diseases. Results
      demonstrate that existing medical conditions may worsen and subsequently improve,
      new diseases may develop, and risk factors, such as weight and cholesterol
      levels, may increase for several years after an earthquake and/or tsunami. We
      make 3 recommendations for practitioners and researchers: (1) plan for
      noncommunicable disease management further into the recovery period of disaster;
      (2) increase research on the burden of noncommunicable diseases, the treatment
      modalities employed, resulting population-level outcomes in the postdisaster
      setting, and existing models to improve stakeholder coordination and action
      regarding noncommunicable diseases after disasters; and (3) coordinate with
      preexisting provision networks, especially primary care.

PMID- 29355395
TI  - Common structural and pharmacophoric features of mPGES-1 and LTC4S.
AB  - Prostaglandins and leukotrienes are produced in the COX and 5-LOX pathways of the
      inflammatory process. The current drugs target the upstream enzymes of either of
      the two pathways, leading to side effects. We have attempted to target the
      downstream enzymes simultaneously. Two compounds 2 and 3 (10 MUM), identified by
      virtual screening, inhibited mPGES-1 activity by 53.4 +/- 4.0 and 53.9 +/- 8.1%,
      respectively. Structural and pharmacophore studies revealed a set of common
      residues between LTC4S and mPGES-1 as well as four-point pharmacophore mapping
      onto the inhibitors of both these enzymes as well as 2 and 3. These structural
      and pharmacophoric features may be exploited for ligand- and structure-based
      screening of inhibitors and designing of dual inhibitors.

PMID- 29355396
TI  - Male perception about the inconveniences associated with monthly bleeding for
      their partner - an international survey.
AB  - OBJECTIVE: To assess men's perceptions about monthly bleeding and associated
      inconveniences for their partner, as well as men's attitudes regarding the
      desired menstruation frequency for their partner and knowledge about hormonal
      contraceptives. METHODS: A 15 min quantitative online survey was conducted among
      5044 men aged 18-45 years, who had been in a relationship for more than 6 months,
      across 13 European countries (Austria, Belgium, Czech Republic, France, Germany,
      Hungary, Italy, Latvia, The Netherlands, Poland, Portugal, Spain and
      Switzerland). Responses were compared to those obtained in a similar study among
      European women. RESULTS: Most men perceived that their partner considered her
      menstrual flow as moderate, lasting an average of 5.2 d, slightly longer than
      previously reported by women. Almost all men reported that their partners
      experience menstruation-related symptoms. However, prevalence of mood-related
      symptoms was perceived to be more frequent and physical symptoms less frequent,
      relative to women's self-reported symptoms. Given the option, 71% of men would
      choose longer intervals between their partner's periods. Maintaining the couple's
      sex life, social life and relationship quality were key factors cited in their
      preference. Overall, 42% of respondents stated that women taking hormonal
      contraceptives needed to have monthly periods. CONCLUSIONS: Men's perception
      regarding their partner's periods was generally consistent with that previously
      reported by women. Most men would prefer less frequent bleeding episodes for
      their partners. Although, the present data suggest that couples are discussing
      periods, knowledge about contraception could be improved. Health care
      professionals should intensify counselling to better inform both partners about
      their contraceptive options.

PMID- 29355397
TI  - Validation of S100B use in a cohort of Spanish patients with mild traumatic brain
      injury: a multicentre study.
AB  - INTRODUCTION: The aim of this study was to validate the S100B protein as a
      diagnostic tool for ruling out the presence of intracranial lesion (IL) after
      mild traumatic brain injury (mTBI). Subjects with a Glasgow Coma Scale (GCS)
      score of 15 and at least one neurological symptom post-trauma were selected from
      a large Spanish cohort. METHODS: A number of 260 patients with mTBI were
      enrolled. Blood samples were extracted within 6 h and CT scan performed within 24
      h post-injury. Blood samples were also drawn from 18 healthy subjects. RESULTS:
      CT scan revealed the presence of IL in 22 patients (8.5%). Patients with mTBI had
      higher S100B serum levels (p = 0.008) than the healthy subjects (p < 0.001). The
      ROC analysis of S100B discriminated between patients with and without IL (AUC:
      0.671; 95%CI: 0.574-0.769; p = 0.008). The multivariate analysis identified male
      gender (OR: 5.39; 95%CI: 1.45-20.10; p = 0.012), age > 65 (OR: 2.97; 95%CI: 1.04
      8.44; p = 0.041) and S100B level >0.10 ug/L (OR: 7.93; 95%CI: 1.03-60.76; p =
      0.046) as independent risk factors for IL in patients with mTBI. CONCLUSION:
      Measurement of S100B within 6 h of mTBI accurately predicts risk of IL in
      patients with a GCS score of 15 and at least one neurological symptom.

PMID- 29355398
TI  - Using Twitter to access the human right of communication for people who use
      Augmentative and Alternative Communication (AAC).
AB  - PURPOSE: Articles 19, 26 and 27 of the Universal Declaration of Human Rights and
      Articles 4, 9 and 21 of the Convention on the Rights of Persons with Disabilities
      promote the human rights of communication, education, use of technology and
      access to information. Social media is an important form of online communication,
      and Twitter increases users' visibility, influence and reach online. The aim of
      this sociotechnical research was to determine the impact of teaching three people
      who use Augmentative and Alternative Communication (AAC) to use Twitter. METHOD:
      Three participants were trained in ways of using Twitter strategically. Data
      collected from participants' Twitter profiles were examined to determine the
      impact of training on Twitter follower count, frequency of tweeting, tweet
      content and the development of social networks. Data were also examined using (1)
      KH Coder software analysis and visualisation of co-occurring networks in the text
      data, based on word frequencies; and (2) Gephi software analysis to show the
      Twitter network for each participant. RESULT: Two participants showed an
      improvement in Twitter skills and strategies. CONCLUSIONS: Twitter can be used to
      improve social connectedness of people who use AAC, and should not be overlooked
      in relation to communication rights.

PMID- 29355399
TI  - Helmet use in preventing acute concussive symptoms in recreational vehicle
      related head trauma.
AB  - OBJECTIVES: Helmets use has proved effective in reducing head trauma (HT)
      severity in children riding non-motorised recreational vehicles. Scant data are
      available on their role in reducing concussive symptoms in children with HT while
      riding non-motorised recreational vehicles such as bicycles, push scooters and
      skateboards (BSS). We aimed to investigate whether helmet use is associated with
      a reduction in acute concussive symptoms in children with BSS-related-HT.
      METHODS: Prospective study of children <18 years who presented with a BSS related
      HT between April 2011 and January 2014 at a tertiary Paediatric Emergency
      Department (ED). RESULTS: We included 190 patients. Median age 9.4 years (IQR 4.8
      13.8). 66% were riding a bicycle, 23% a push scooter, and 11% a skateboard. 62%
      were wearing a helmet and 62% had at least one concussive symptom. Multivariate
      logistic regression analysis adjusting for age, gender, and type of vehicle
      showed that patients without a helmet presented more likely with headache
      (adjusted odds-ratio (aOR) 2.54, 95% CI 1.27-5.06), vomiting (aOR 2.16, 95% CI
      1.00-4.66), abnormal behaviour (aOR 2.34, 95% CI 1.08-5.06), or the presence of
      at least one concussive symptom (aOR 2.39, 95% CI 1.20-4.80). CONCLUSIONS: In
      children presenting to the ED following a wheeled BSS-related HT helmet use was
      associated with less acute concussive symptoms. ABBREVIATIONS: aOR, adjusted odds
      ratio; APHIRST, Australasian Paediatric Head Injury Rules Study; BSS, bicycles,
      push scooters and skateboards; CI, confidence interval; CT, computed tomography;
      ED, emergency department; HT, head trauma; IQR, interquartile range; OR, odds
      ratio; RCH, Royal Children's Hospital; RV, recreational vehicle.

PMID- 29355400
TI  - Clinical efficacy of ribociclib as a first-line therapy for HR-positive, advanced
      breast cancer.
AB  - INTRODUCTION: Breast cancer (BC) remains the most frequently diagnosed cancer and
      the most common cause of cancer death among women of all races worldwide. Over
      80% of BC cases are hormone receptor (HR)-positive, comprised of luminal A and
      luminal B per molecular subtypes, imposing an urgent need to fully understand the
      mechanisms behind progression. Ribociclib is a selective cycline-dependent kinase
      4 and 6 inhibitor. A phase 1 and a phase 3 trial have established a definitive
      role of ribociclib as frontline in the treatment of endocrine-sensitive advanced
      BC. Areas covered: Herein, the authors provide an overview of the data on
      ribociclib covering all aspects of the drug from its pharmacokinetics to efficacy
      and safety. The authors also provide their perspectives for the future. Expert
      opinion: Ribociclib is offering an opportunity to explore a new compound at the
      crossroads of different molecular activity and cell targets, which focus on
      endocrine-resistance reversal in multiple settings including early BC. Moreover,
      its activity against different subtypes of BC is being studied as is its immune
      modulating effect. One cautionary note is that, in a market of concomitant
      similar competitors, a financial discussion will be mandatory.

PMID- 29355401
TI  - Lesions Without Borders: Scrotal Lesions That Involve Both the Intratesticular
      and Extratesticular Regions.
AB  - OBJECTIVE: Differentiation of scrotal lesions is often dictated by whether they
      are intraor extratesticular. However, these regions are not entirely isolated,
      and disease processes can span both spaces. We review a variety of lesions that
      can involve both regions, describe the relevant anatomy, and illustrate their
      imaging appearances. CONCLUSION: Identification of involvement of both intra- and
      extratesticular regions by a single process can narrow the differential
      considerations and help arrive at the correct diagnosis.

PMID- 29355402
TI  - Section Editor's Notebook: Breast Cancer Screening-What Now, and What Next?

PMID- 29355403
TI  - Memorial-A. Everette James, Jr.

PMID- 29355404
TI  - Medicolegal-Malpractice and Ethical Issues in RadiologyFaster Radiologic
      Interpretation, Errors, and Malpractice: An Unavoidable Triad?

PMID- 29355405
TI  - Additional Roles of Tomosynthesis in Breast Imaging-Guided Biopsies.

PMID- 29355406
TI  - AJR Reviewers: Thank You From the Editors and Staff.

PMID- 29355407
TI  - Introduction to ICNARA 3.

PMID- 29355408
TI  - Getting to Know "The Known Unknowns": Heterogeneity in the Oral Microbiome.
AB  - Technological advances in DNA sequencing have provided unprecedented insights
      into the composition of the oral microbiome in health and disease, and RNA
      sequencing and metabolomics-related technologies are beginning to yield
      information on the activities of these organisms. Importantly, progress in this
      area has brought the scientific community closer to an understanding of what
      constitutes a health-associated microbiome and is supporting the notion that the
      microbiota in healthy sites assumes an active role in promoting health and
      suppressing the acquisition, persistence, and activities of overt and
      opportunistic pathogens. It is also becoming clear that a significant impediment
      to developing a conclusive body of evidence that defines a healthy microbiome and
      the mechanisms by which beneficial bacteria promote health is that an inherent
      characteristic of the most abundant members of the oral flora, those that
      potentially play the greatest roles in health and disease, is intraspecies
      genomic diversity. In particular, individual isolates of abundant commensal and
      pathogenic streptococci show tremendous variability in gene content, and this
      variability manifests in tremendous phenotypic heterogeneity. Analysis of the
      consequences of this diversity has been complicated by the exquisite sensitivity
      these bacteria have evolved to environmental inputs, inducing rapid and
      substantial fluctuations in behaviors, and often only within subpopulations of
      the organisms. Thus, the conditions under which the oral microbiota is studied
      can produce widely different results within and between species. Fortunately,
      continually diminishing costs and ongoing refinements in sequencing and
      metabolomics are making it practical to study the oral microbiome at a level that
      will create a sufficiently robust understanding of the functions of individual
      organisms and reveal the complex interrelationships of these microbes ("the known
      unknowns") in a way that researchers will be able to engage in the rational
      design of reliable and economical risk assessments and preventive therapies.

PMID- 29355409
TI  - Changes in Caries Risk in a Practice-Based Randomized Controlled Trial.
AB  - To demonstrate that Caries Management by Risk Assessment (CAMBRA) can be
      successfully implemented in dental practice, 30 dentists were recruited to
      perform a 2-y CAMBRA trial. Twenty-one dentists (18 private practices, 3
      community clinics) participated in a randomized, controlled, parallel-arm, double
      blind clinical trial with individual-level assignment of 460 participants to
      standard of care (control) versus active CAMBRA treatment (intervention). Control
      or active antimicrobial and remineralizing agents were dispensed at baseline and
      6-, 12-, 18-, and 24-mo recall visits according to risk level and assigned
      treatment arm. Primary outcome measure was dentist-determined caries risk level
      at recall. Among initially high-risk participants, secondary outcomes were
      recorded disease indicators. Generalized estimating equations were used to fit
      log-linear models for each outcome while accounting for repeated measurements. At
      24 mo, follow-up rates were 34.3% for high-risk participants (32.1% intervention,
      37.1% control) and 44.2% for low-risk participants (38.7% intervention, 49.5%
      control). Among 242 participants classified as high caries risk at baseline (137
      intervention, 105 control), a lower percentage of participants remained at high
      risk in the intervention group (statistically significant at all time points). At
      24 mo, 25% in the intervention group and 54% in the control group remained at
      high risk ( P = 0.003). Among 192 participants initially classified as low risk
      (93 intervention, 99 control), most participants remained at low risk. At 24 mo,
      89% in the intervention group and 71% in the control group were low caries risk (
      P = 0.18). The percentage of initially high-risk participants with recorded
      disease indicators decreased over time in both intervention and control groups,
      being always lower for the intervention group (statistically significant at the
      12- and 18-mo time point). In this practice-based clinical trial, a significantly
      greater percentage of high-caries-risk participants were classified at a lower
      risk level after CAMBRA preventive therapies were provided. Most participants
      initially assessed at low caries risk stayed at low risk (ClinicalTrials.gov
      NCT01176396).

PMID- 29355410
TI  - In Sickness and in Health-What Does the Oral Microbiome Mean to Us? An Ecological
      Perspective.
AB  - The oral microbiome is natural and has a symbiotic relationship with the host by
      delivering important benefits. In oral health, a dynamic balance is reached
      between the host, the environment, and the microbiome. However, the frequent
      intake of sugar and/or reductions in saliva flow results in extended periods of
      low pH in the biofilm, which disrupts this symbiotic relationship. Such
      conditions inhibit the growth of beneficial species and drive the selection of
      bacteria with an acid-producing/acid-tolerating phenotype, thereby increasing the
      risk of caries (dysbiosis). A more detailed understanding of the
      interdependencies and interactions that exist among the resident microbiota in
      dental biofilms, and an increased awareness of the relationship between the host
      and the oral microbiome, is providing new insights and fresh opportunities to
      promote symbiosis and prevent dysbiosis. These include modifying the oral
      microbiome (e.g., with prebiotics and probiotics), manipulating the oral
      environment to selectively favor the growth of beneficial species, and moderating
      the growth and metabolism of the biofilm to reduce the likelihood of dysbiosis.
      Evidence is provided to suggest that the regular provision of interventions that
      deliver small but relevant benefits, consistently over a prolonged period, can
      support the maintenance of a symbiotic oral microbiome.

PMID- 29355411
TI  - Potential Uses of Arginine in Dentistry.
AB  - Carious lesions develop in tooth surfaces where there is an imbalance of the
      processes of acid and alkali production by supragingival biofilms. Since low pH
      is the main driving factor in the development of carious lesions, most efforts to
      identify an effective anticaries therapy have focused on targeting the acid
      producing bacteria and their mechanisms of acid production. An expanding area of
      oral microbiology has now been devoted to explore microbial metabolic activities
      that help to neutralize biofilm pH and thus inhibit the caries process. Arginine
      metabolism via the arginine deiminase pathway (ADS) produces alkali in the form
      of ammonia that counteracts the effects of biofilm acidification from bacterial
      glycolysis. ADS also functions as an adaptive strategy used by certain bacteria
      to thrive in oral biofilms. Substantial evidence accumulated from laboratory and
      clinical observations supports the hypotheses that measurements of arginine
      metabolism via ADS may serve as an important caries risk assessment criterion and
      that providing arginine regularly to supragingival biofilms can be an effective
      therapy for caries intervention. This article reviews the potential of arginine
      based therapies such as the use of arginine as prebiotic, ADS+ strains as
      probiotics, and oral care formulations containing arginine for prevention and
      management of dental caries.

PMID- 29355412
TI  - Fluoride Use in Health Care Settings: Association with Children's Caries Risk.
AB  - Expanded partnership with the medical community is an important strategy for
      reducing dental caries disparities. The purpose of this study was to assess the
      relationship between fluoride (F) "in office" (drops/tablets and/or varnish), as
      prescribed or applied by a health care professional by age 1 y, and 1) caries
      development and 2) presence of other caries risk factors or mediators (e.g.,
      socioeconomic status). Child-primary caregiver (PCG) pairs ( N = 1,325) were
      recruited in Indiana, Iowa, and North Carolina as part of a longitudinal cohort
      study to validate a caries risk tool for primary health care settings. PCGs
      completed a caries risk questionnaire, while children received caries
      examinations per the criteria of the International Caries Detection and
      Assessment System at ages 1, 2.5, and 4 y. Baseline responses regarding
      children's history of F in office were tested for association with other caries
      risk variables and caries experience at ages 2.5 and 4 y via generalized
      estimating equation models applied to logistic regression. The sample was 48%
      female, and many children (61%) were Medicaid enrolled. The prevalence of
      cavitated caries lesions increased from 7% at age 2.5 y to 25% by age 4 y.
      Children who received F in office were likely deemed at higher caries risk and
      indeed were significantly ( P < 0.01) more likely to develop cavitated caries
      lesions by ages 2.5 and 4 y, even after F application (odds ratios: 3.5 and 2.3,
      respectively). Factors significantly associated with receiving F included the
      following: child being Medicaid enrolled, not having an employed adult in the
      household, child and PCG often consuming sugary drinks and snacks, and PCG having
      recent caries experience. Increased F in office from a health care provider by
      age 1 y was associated with known caries risk factors. Most (69%) children had
      never been to the dentist, suggesting that risk factors could be alerting medical
      providers and/or parents, thereby affecting in-office F recommendations.
      Differences among states could also be related to state-specific F-varnish
      reimbursement policies (ClinicalTrials.gov NCT01707797).

PMID- 29355413
TI  - Treatment of Carious Lesions Using Self-Assembling Peptides.
AB  - Modern approaches in caries treatment involve lesion management without tissue
      removal. Regenerative medicine focuses on replacing damaged tissues with
      biologically similar tissues. This article discusses the scientific evidence and
      clinical results for self-assembling peptides in modern caries management. The
      biomimetic remineralization promoted by self-assembling peptide P11-4 has been
      proven in vitro as an effective therapy for initial caries. P11-4 was rationally
      designed to promote formation of hydroxyapatite on its surface. The formulation
      was optimized to ensure the ability of monomeric P11-4 to penetrate past the
      subsurface lesions and assembly into a biomatrix within. Furthermore, P11-4 has
      shown that it assembles into fibers within carious lesions, and promotes the
      remineralization thereof. In a recent clinical study, the safety and efficacy of
      P11-4 in treatment of initial caries were evaluated. The additional effect of the
      application of P11-4 (Curodont Repair) was compared to the application of
      fluoride varnish (Duraphat) alone in active occlusal initial caries lesions on
      erupting permanent molars. In the 3- and 6-month recalls, the test group showed,
      both in the laser fluorescence readings and in the clinical assessment of the
      caries stage and activity, significantly superior lesion regression compared to
      the control group. No adverse events, medical complications, or allergic
      reactions related to the treatments were reported. Clinical applicability of
      treatment was regarded as satisfactory. Patients were happy to receive
      noninvasive caries treatments. In conclusion, biomimetic mineralization
      facilitated by P11-4 in combination with fluoride may present a simple, safe, and
      effective noninvasive treatment for early carious lesions.

PMID- 29355414
TI  - The Caries Microbiome: Implications for Reversing Dysbiosis.
AB  - The oral microbiome plays a critical role in maintaining oral health. Frequent
      dietary carbohydrate intake can lead to dysbiosis of the microbial community from
      overproduction of acid with selection for increases in acidogenic, acid-tolerant
      bacteria. Knowledge of the caries-associated microbiome is key in planning
      approaches to reverse the dysbiosis to achieve health. For risk assessment and
      treatment studies, it would be valuable to establish whether microbial monitoring
      requires assay of multiple species or whether selected key species would suffice.
      Early investigations of the oral microbiota relied on culture-based methods to
      determine the major bacteria in health and disease. Microbial monitoring using
      gene probes facilitated study of larger populations. DNA probe methods confirmed
      and expanded the importance of transmission of bacteria from mother to infant and
      association of preselected species, including mutans streptococci and
      lactobacilli with caries in larger populations. 16S ribosomal RNA (rRNA) probes
      confirmed the wide diversity of species in oral and caries microbiomes. Open
      ended techniques provide tools for discovery of new species, particularly when
      strain/clone identification includes gene sequence data. Anaerobic culture
      highlighted the caries association of Actinomyces and related species. Scardovia
      wiggsiae, in the Actinomyces/Bifidobacterium family, and several Actinomyces
      species have the cariogenic traits of acid production and acid tolerance. Next
      generation sequencing combined with polymerase chain reaction methods revealed a
      strong association with mutans streptococci in a high caries population with poor
      oral hygiene and limited access to care. A population with a lower caries
      experience generally had lower or no Streptococcus mutans detection but harbored
      other acidogenic taxa in the microbiome. Study of the microbiome suggests a role
      for the assay of selected putative cariogenic species in more aggressive
      diseases. For many populations with caries progression, however, assay of
      multiple species will likely be warranted to determine the caries profile of the
      population and/or individuals under study.

PMID- 29355415
TI  - Cariology Clinical Trials: What Are We-and What Should We Be-Looking At?
AB  - Randomized control trial (RCT) methodology has compared interventions for the
      prevention and management of dental caries since the late 1960s. Despite almost
      50 years and evidence of significant wastage within the wider biomedical research
      field, there has been little investigation into what works well and where
      weaknesses lie. This paper aims to draw attention to areas for improvement within
      cariology clinical trial methodology by summarizing systematic reviews on
      interventions and outcomes, and using examples to illustrate some challenges with
      intervention delivery fidelity, outcome analyses, and intervention co-production.
      Trial design stage choices are critical to ensure that optimum information is
      obtained when testing interventions. Intervention choice, outcome choice, and
      analyses are particularly important, and cariology trials have specific issues
      associated with them. A systematic search and review of cariology RCTs found 650
      RCT reports. Social Network Analysis of interventions revealed a high degree of
      separation between prevention and management trials, gaps in clinically important
      comparisons, and a tendency for there to be comparisons within groups; e.g.,
      comparison of interventions within the same, rather than different, levels of
      invasiveness. Outcomes measured for the same trial reports show: a focus on
      restoration performance and individual/population caries burden; the growing use
      of carious lesion activity and economic-related outcomes; and sparse, although an
      increase in the use of, patient-reported/patient-centered outcomes. Fidelity of
      adherence to complex interventions can be challenging to measure but is important
      in interpreting trial findings. Involving target populations in intervention
      design, delivery, and relating it to the planned rollout, are opportunities to
      ensure intervention relevance and improved uptake. Outcomes analyses should
      consider the minimum clinically important differences and outcome relevance
      measures for the target population. Factors underlying trialists' comparator and
      outcome choices need to be identified, and there is a need to ensure that a
      minimum dataset of outcomes allow for combination and comparisons of trial data
      for systematic review.

PMID- 29355416
TI  - Antimicrobial Activity of a Colloidal AgNP Suspension Demonstrated In Vitro
      against Monoculture Biofilms: Toward a Novel Tooth Disinfectant for Treating
      Dental Caries.
AB  - A novel silver nanoparticle (AgNP) formulation was developed as a targeted
      application for the disinfection of carious dentine. Silver nitrate (AgNO3) was
      chemically reduced using sodium borohydrate (NaBH4) in the presence of sodium
      dodecyl sulfate (SDS) to form micelle aggregate structures containing
      monodisperse 6.7- to 9.2-nm stabilized AgNPs. AgNPs were characterized by
      measurement of electrical conductivity and dynamic light scattering, scanning
      electron microscopy, transmission electron microscopy, and inductively coupled
      plasma mass spectrometry. Antimicrobial activity of AgNPs was tested against
      planktonic cultures of representative gram-positive and gram-negative oral
      bacteria using well diffusion assays on tryptic soy broth media and monoculture
      biofilms grown with brain heart infusion +/- sucrose anaerobically at 37 degrees
      C on microtiter plates. Biofilm mass was measured by crystal violet assay.
      Effects were compared to silver diamine fluoride and chlorhexidine (negative
      controls) and 70% isopropanol (positive control) exposed cultures. In the
      presence of AgNPs, triplicate testing against Streptococcus gordonii DL1, C219,
      G102, and ATCC10558 strains; Streptococcus mutans UA159; Streptococcus mitis I18;
      and Enterococcus faecalis JH22 for planktonic bacteria, the minimum inhibitory
      concentrations were as low as 7.6 ug mL-1 and the minimum bacteriocidal
      concentrations as low as 19.2 ug mL-1 silver concentration. Microplate readings
      detecting crystal violet light absorption at 590 nm showed statistically
      significant differences between AgNP-exposed biofilms and where no antimicrobial
      agents were used. The presence of sucrose did not influence the sensitivity of
      any of the bacteria. By preventing in vitro biofilm formation for several
      Streptococcus spp. and E. faecalis, this AgNP formulation demonstrates potential
      for clinical application inhibiting biofilms.

PMID- 29355417
TI  - Reminova and EAER: Keeping Enamel Whole through Caries Remineralization.
AB  - This article aims to outline the early development of a King's College London
      dental spinout company, Reminova, formed to commercialize a novel clinical method
      of caries remineralization: electrically accelerated and enhanced
      remineralization (EAER). This method is being developed to address the unmet
      clinical need identified by modern caries management strategies to keep enamel
      "whole" through remineralization of clinical caries as a form of nonoperative
      caries treatment for initial-stage and moderate lesions. A progressive movement
      within dentistry is shifting away from the restorative-only model, which, it is
      suggested, has failed. The high prevalence of initial-stage caries across
      populations provides a significant opportunity to prevent restorations and reduce
      repeat restorations over a patient's lifetime. Reminova has set out to provide a
      method to repair lesions without drilling, filling, pain, or injections. The
      article outlines the rationale for and the chronological stages of the technology
      and company development. It then outlines corroborative evidence to show that
      EAER treatment can, in this preliminary in vitro investigation, remineralize
      clinically significant caries throughout the depth of the lesion as measured by
      Knoop microhardness and corroborated by scanning electron microscopy.
      Furthermore, the presented data show that EAER-treated enamel is harder than the
      healthy enamel measured nearby in each sample and is very similar in appearance
      to healthy enamel from the subjective interpretation made possible by scanning
      electron microscopy imagery. The data presented also show that this more
      "complete" remineralization to a high hardness level has been achieved with 2
      remineralizing agents via in vitro human tooth samples. The broad clinical
      potential of this new treatment methodology seems to be very encouraging from
      these results. Reminova will strive to continue its mission, to ensure that, in
      the future, dental teams will not need to drill holes for the treatment of
      initial-stage and moderate caries lesions.

PMID- 29355418
TI  - Rebalancing the Caries Microbiome Dysbiosis: Targeted Treatment and Sugar
      Alcohols.
AB  - Dental caries is a disease that results from microbiome dysbiosis with the
      involvement of multiple cariogenic species, including mutans streptococci (MS),
      lactobacilli, Scardovia wiggsiae, and several Actinomyces species that have the
      cariogenic traits of acid production and acid tolerance. Sugar consumption also
      plays an important role interacting with microbiome dysbiosis, determining the
      fate of caries development. In addition, the MS transmission that encompasses
      multiple sources can have long-term impacts on the oral microbiome and caries
      development in children. Intervention in MS transmission in early childhood may
      promote effective long-term caries prevention. Anticaries regimens aimed against
      the above mechanisms will be important for successful caries management. Xylitol
      and erythritol may serve as good components of anticaries regimens as oral
      microbiome modifiers, sugar substitutes, and agents to prevent MS transmission in
      early childhood with both oral and systemic benefits. Further studies are needed
      to elucidate the mechanism of the anticaries effects of xylitol and erythritol
      with consideration of their impacts on the microbiome and bacterial virulence, in
      addition to cariogenic bacteria levels as well as their benefits for overall
      health. On the other hand, the anticaries agent C16G2, specifically targeting
      Streptococcus mutans, the most common cariogenic bacterial species, has shown
      good safety for short-term oral topical use and promising effects in reducing S.
      mutans in vitro and in vivo with the promotion of oral commensal bacteria. Future
      study on its anticaries effect will need to include its long-term impact on the
      oral microbiome and effects on other important cariogenic bacteria.

PMID- 29355419
TI  - Dentist-Perceived Barriers and Attractors to Cognitive-Behavioral Treatment
      Provided by Mental Health Providers in Dental Practices.
AB  - Over 1 in 5 dental patients report moderate to severe dental fear. Although the
      efficacy of cognitive-behavioral treatment (CBT) for dental fear has been
      examined in over 20 randomized controlled trials-with 2 meta-analyses finding
      strong average effect sizes ( d > 1)-CBT has received almost no dissemination
      beyond the specialty clinics that tested it. The challenge, then, is not how to
      treat dental fear but how to disseminate and implement such an evidence-based
      treatment in a way that recognizes the rewards and barriers in the US health care
      system. This mixed-method study investigated the potential of disseminating CBT
      through care from a mental health provider from within the dental home, a
      practice known as evidence-based collaborative care (EBCC). Two preadoption
      studies were conducted with practicing dentists drawn from a self-organized
      Practice-Based Research Network in the New York City metropolitan area. The first
      comprised 3 focus groups ( N = 17), and the second involved the administration of
      a survey ( N = 46). Focus group participants agreed that CBT for dental fear is
      worthy of consideration but identified several concerns regarding its appeal,
      feasibility, and application in community dental practices. Survey participants
      indicated endorsement of factors promoting the use of EBCC as a mechanism for CBT
      dissemination, with no factors receiving less than 50% support. Taken together,
      these findings indicate that EBCC may be a useful framework through which an
      evidence-based treatment for dental fear treatment can be delivered.

PMID- 29355420
TI  - The Anticaries Efficacy of a 1.5% Arginine and Fluoride Toothpaste.
AB  - Dental caries remains a world-wide disease despite the global distribution of
      fluoride. It has become apparent that the introduction of significant levels of
      sugar (fermentable carbohydrate) into the diet has resulted in a change in the
      biofilm, encouraging acid formation. Further, there has been a shift in the
      microbiota in the biofilm to a flora that produces acid, and thrives and
      reproduces in an acidic environment. The management of caries activity under
      these conditions has focused on brushing to remove the biofilm with fluoride
      pastes, and high-dose fluoride treatments. Kleinberg, in the 1970s, identified an
      arginine-containing compound in saliva that several oral biofilm bacterial
      species metabolize to produce base. Multiple in situ and in vivo studies have
      been conducted, and have discussed the ability of multiple bacteria to increase
      the resting pH of the biofilm and even reduce the decrease in pH when the biofilm
      is challenged with glucose. This shift in resting pH can shift the level of
      caries formation by the biofilm. Here, we present 8 clinical studies, with
      different clinical designs, measuring different clinical outcomes, for a diverse,
      world-wide population. Each of these studies demonstrates reductions in caries
      formation beyond that seen with fluoride alone and several demonstrate the
      reversal of early caries lesions. Significant clinical research has been shown
      that 1.5% arginine combined with fluoride toothpaste has superior anti-caries
      efficacy to toothpaste containing fluoride alone.

PMID- 29355422
TI  - Oral Microbiome Studies: Potential Diagnostic and Therapeutic Implications.
AB  - Understanding the microbiology of dental caries is not a mere academic exercise;
      it provides the basis for preventive, diagnostic, and treatment strategies and
      gives the dentist a theoretical framework to become a better professional. The
      last years have seen the development of new research methodologies, ranging from
      high-throughput sequencing or "omics" techniques to new fluorescence microscopy
      applications and microfluidics, which have allowed the study of the oral
      microbiome to an unprecedented level of detail. Those studies have provided new
      insights about oral biofilm formation, biomarkers of caries risk, microbial
      etiology, appropriate sampling, identification of health-associated bacteria, and
      new anticaries strategies, among others. Several pitfalls are associated with the
      new technologies, including a small number of samples per study group, elevated
      cost, and genus- or species-based analyses that do not take into consideration
      intraspecies variability. However, the new data strongly suggest that saliva may
      not be an appropriate sample for etiological studies or for bacterial caries-risk
      tests, that microbial composition alone may be insufficient to predict caries
      risk, and that antimicrobial or immunization strategies targeting single species
      are unlikely to be effective. Strategies directed toward modulation of the oral
      biofilm, such as pre- and probiotics, emerge as promising new approaches to
      prevent tooth decay.

PMID- 29355421
TI  - Therapeutic Strategies Targeting Cariogenic Biofilm Microenvironment.
AB  - Cariogenic biofilms are highly structured microbial communities embedded in an
      extracellular matrix, a multifunctional scaffold that is essential for the
      existence of the biofilm lifestyle and full expression of virulence. The
      extracellular matrix provides the physical and biological properties that enhance
      biofilm adhesion and cohesion, as well as create a diffusion-modulating milieu,
      protecting the resident microbes and facilitating the formation of localized
      acidic pH niches. These biochemical properties pose significant challenges for
      the development of effective antibiofilm therapeutics to control dental caries.
      Conventional approaches focusing solely on antimicrobial activity or enhancing
      remineralization may not achieve maximal efficacy within the complex biofilm
      microenvironment. Recent approaches disrupting the biofilm microbial community
      and the microenvironment have emerged, including specific targeting of cariogenic
      pathogens, modulation of biofilm pH, and synergistic combination of bacterial
      killing and matrix degradation. Furthermore, new "smart" nanotechnologies that
      trigger drug release or activation in response to acidic pH are being developed
      that could enhance the efficacy of current and prospective chemical modalities.
      Therapeutic strategies that can locally disrupt the pathogenic niche by targeting
      the biofilm structure and its microenvironment to eliminate the embedded
      microorganism and facilitate the action of remineralizing agents may lead to
      enhanced and precise anticaries approaches.

PMID- 29355423
TI  - The Evidence for Caries Management by Risk Assessment (CAMBRA(r)).
AB  - A system for Caries Management by Risk Assessment (CAMBRA(r)) has been developed
      in California. The purpose of this article is to summarize the science behind the
      methodology, the history of the development of CAMBRA, and the outcomes of
      clinical application. The CAMBRA caries risk assessment (CRA) tool for ages 6 y
      through adult has been used at the University of California, San Francisco
      (UCSF), for 14 y, and outcome studies involving thousands of patients have been
      conducted. Three outcomes assessments, each on different patient cohorts,
      demonstrated a clear relationship between CAMBRA-CRA risk levels of low,
      moderate, high, and extreme with cavitation or lesions into dentin (by
      radiograph) at follow-up. This validated risk prediction tool has been updated
      with time and is now routinely used at UCSF and in other settings worldwide as
      part of normal clinical practice. The CAMBRA-CRA tool for 0- to 5-y-olds has
      demonstrated similar predictive validity and is in routine use. The addition of
      chemical therapy (antibacterial plus fluoride) to the traditional restorative
      treatment plan, based on caries risk status, has been shown to reduce the caries
      increment by about 20% to 38% in high-caries-risk adult patients. The chemical
      therapy used for high-risk patients is a combination of daily antibacterial
      therapy (0.12% w/v chlorhexidine gluconate mouth rinse) and twice-daily high
      concentration fluoride toothpaste (5,000 ppm F), both for home use. These
      outcomes assessments provide the evidence to use these CRA tools with confidence.
      Caries can be managed by adding chemical therapy, based on the assessed caries
      risk level, coupled with necessary restorative procedures. For high- and extreme
      risk patients, a combination of antibacterial and fluoride therapy is necessary.
      The fluoride therapy must be supplemented by antibacterial therapy to reduce the
      bacterial challenge, modify the biofilm, and provide prevention rather than
      continued caries progression.

PMID- 29355424
TI  - Silver Diamine Fluoride: A Successful Anticarious Solution with Limits.
AB  - Silver diamine fluoride (SDF) is a solution containing ionic silver, fluoride,
      and ammonia that arrests the progress of carious lesions and prevents the
      development of future caries. The silver particle extends into the dentin tubules
      and could create some bonding problems for subsequent composite resin
      restorations placed over SDF-treated darkened tooth structures. The fluoride
      penetrates deeper into the tooth with SDF as compared with other fluoride
      solutions, creating a fluoride reservoir in the tooth structure. The fluoride
      component of SDF contributes to remineralization and fluorapatite formation,
      producing harder, more caries-resistant tooth structures. The silver provides the
      antimicrobial activity for the material and inhibits biofilm formation. It has
      been evaluated in >20 clinical studies and reviewed in systemic reviews. The
      material was recently approved by the Food and Drug Administration for
      desensitizing cold-sensitive teeth and has been used off-label to treat carious
      lesions. SDF will produce a caries lesion darker (brown to black) than the
      original, which is the major criticism of the material. A nanoparticle-sized
      silver material was recently developed that may retain the antimicrobial
      properties of the larger-sized ion silver material without the discoloring
      effects. The application of SDF is easily adapted for field use. The lesion is
      isolated, and the solution is painted onto the clean caries lesion and dried.
      This simple application process requires little equipment, and its low cost per
      application makes the material ideal for large populations.

PMID- 29355425
TI  - Erythritol Functional Roles in Oral-Systemic Health.
AB  - Erythritol belongs chemically to the family of polyols (or sugar alcohols), yet
      it is metabolized by animals and humans very differently compared to all other
      polyols. While polyols have been used traditionally (for about 80 y) to replace
      sugar in sweet foods to reduce demineralization of tooth enamel and to reduce
      postprandial blood glucose levels, benefits achieved merely through the absence
      of sugar, emerging evidence shows that erythritol can play a number of functional
      roles to actively support maintenance of oral and systemic health. Oral health
      studies revealed that erythritol can reduce dental plaque weight, reduce dental
      plaque acids, reduce counts of mutans streptococci in saliva and dental plaque,
      and reduce the risk for dental caries better than sorbitol and xylitol, resulting
      in fewer tooth restorations by dentist intervention. Systemic health studies have
      shown that erythritol, unlike other polyols, is readily absorbed from the small
      intestine, not systemically metabolized, and excreted unchanged within the urine.
      This metabolic profile renders erythritol to be noncaloric, to have a high
      gastrointestinal tolerance, and not to increase blood glucose or insulin levels.
      Published evidence also shows that erythritol can act as an antioxidant and that
      it may improve endothelial function in people with type 2 diabetes. This article
      reviews the key research demonstrating erythritol's oral and systemic health
      functionalities and underlying mechanisms.

PMID- 29355426
TI  - Recent Advances in Remineralization Therapies for Caries Lesions.
AB  - Remineralization of caries lesions is naturally achieved by salivary ions, and it
      can be enhanced by external factors or elements such as fluoride. Numerous
      studies have demonstrated the remineralizing efficacy of fluoride therapies as
      well as the limitations with some groups of the population. Consequently,
      developing new remineralization therapies to close this gap in efficacy has been
      a priority for the last 2 decades. In this review, we summarize and briefly
      discuss some of the latest advances in remineralization therapies. Most new
      therapies try to enhance the effect of fluoride by adding other potentially
      active ingredients to the formulation, such as calcium, phosphate, stannous,
      xylitol, and arginine. Other remineralization strategies have focused on creating
      remineralizing scaffolds within the lesions (e.g., self-assembling peptides).
      While several of the new remineralization strategies have progressed
      significantly in recent years, for most of them, the evidence is still
      insufficient to assess their true clinical potential.

PMID- 29355427
TI  - Stannous Fluoride Effects on Gene Expression of Streptococcus mutans and
      Actinomyces viscosus.
AB  - A genome-wide transcriptional analysis was performed to elucidate the bacterial
      cellular response of Streptococcus mutans and Actinomyces viscosus to NaF and
      SnF2. The minimal inhibitory concentration (MIC) and minimal bactericidal
      concentration (MBC) of SnF2 were predetermined before microarray study. Gene
      expression profiling microarray experiments were carried out in the absence
      (control) and presence (experimental) of 10 ppm and 100 ppm Sn2+ (in the form of
      SnF2) and fluoride controls for 10-min exposures (4 biological
      replicates/treatment). These Sn2+ levels and treatment time were chosen because
      they have been shown to slow bacterial growth of S. mutans (10 ppm) and A.
      viscosus (100 ppm) without affecting cell viability. All data generated by
      microarray experiments were analyzed with bioinformatics tools by applying the
      following criteria: 1) a q value should be <=0.05, and 2) an absolute fold change
      in transcript level should be >=1.5. Microarray results showed SnF2 significantly
      inhibited several genes encoding enzymes of the galactose pathway upon a 10-min
      exposure versus a negative control: lacA and lacB (A and B subunits of the
      galactose-6-P isomerase), lacC (tagatose-6-P kinase), lacD (tagatose-1,6-bP
      adolase), galK (galactokinase), galT (galactose-1-phosphate uridylyltransferase),
      and galE (UDP-glucose 4-epimerase). A gene fruK encoding fructose-1-phosphate
      kinase in the fructose pathway was also significantly inhibited. Several genes
      encoding fructose/mannose-specific enzyme IIABC components in the
      phosphotransferase system (PTS) were also downregulated, as was ldh encoding
      lactate dehydrogenase, a key enzyme involved in lactic acid synthesis. SnF2
      downregulated the transcription of most key enzyme genes involved in the
      galactose pathway and also suppressed several key genes involved in the PTS,
      which transports sugars into the cell in the first step of glycolysis.

PMID- 29355428
TI  - Silver Fluoride as a Treatment for Dental Caries.
AB  - Medical management of caries is a distinct treatment philosophy that employs
      topical minimally invasive therapies that treat the disease and is not merely
      prevention. This strategy is justified as an alternative or supplement to
      traditional care by significant disease recurrence rates following comprehensive
      operative treatment under general anesthesia. Silver diamine fluoride (SDF) is
      one agent to enable effective noninvasive treatment. The announcement of
      breakthrough therapy designation by the Food and Drug Administration (FDA)
      suggests that SDF may become the first FDA-approved drug for treating caries.
      Since our systematic review performed in April 2015, 4 clinical trials have been
      completed, which inform an update to the application protocol and frequency
      regimen. Suggestions from these studies are to skip the rinsing step due to
      demonstration of safety in young children, start patients with high disease
      severity on an intensive regimen of multiple applications over the first few
      weeks, and continue with semiannual maintenance doses as previously suggested.
      Breakthroughs in elucidating the impact of SDF on the dental plaque microbiome
      inform potential opportunities for understanding caries arrest. SDF can be added
      to the set of evidence-based noninvasive methods to treat caries lesions in
      primary teeth, such as the Hall crown technique and sealing lesions with
      accessible margins.

PMID- 29355429
TI  - The effects of post-traumatic depression on cognition, pain, fatigue, and
      headache after moderate-to-severe traumatic brain injury: a thematic review.
AB  - BACKGROUND: Post-traumatic depression (PTD) is one of the most common secondary
      complications to develop after moderate-to-severe traumatic brain injury (TBI).
      However, it rarely manifests singularly, and often co-occurs with other common
      TBI impairments. OBJECTIVE: The objective of this thematic review is to evaluate
      studies examining the relationships between PTD and cognition, fatigue, pain, and
      headache among individuals with moderate-to-severe TBI. RESULTS: We reviewed 16
      studies examining the relationship between PTD and cognition (five articles),
      fatigue (five articles), pain (four articles), and headache (two articles). Two
      studies failed to identify the significant associations between PTD and
      neuropsychological test performance, while one study found a positive
      association. Two other studies found that early PTD was associated with later
      executive dysfunction. Studies on fatigue suggest it is a cause, not consequence,
      of PTD. Individuals with PTD tended to report more pain than those without PTD.
      Studies examining relationships between PTD and post-traumatic headache were
      equivocal. CONCLUSIONS: Studies evaluating the effects of PTD on common TBI
      impairments have yielded mixed results. Evidence suggests PTD precedes the
      development of executive dysfunction, and a strong link exists between fatigue
      and PTD, with fatigue preceding PTD. Future prospective studies evaluating PTD
      relationships to pain and headache are warranted to elucidate causality.

PMID- 29355430
TI  - Admission circulating monocytes level is an independent predictor of outcome in
      traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to assess the prognostic value of admission
      immune cell levels in the peripheral blood in determining outcomes in patients
      with TBI. METHOD: We studied 141 adult patients with mild-to-severe TBI (Glasgow
      Coma Scale (GCS) 3-15). Patient outcome was assessed using the Extended Glasgow
      Outcome Scale (GOSE) at 6 months post-injury. The area under the curve (AUC) was
      used to evaluate the predictive ability of immune cell levels. Uni- and
      multivariate analyses were performed to assess the independent predictors of 6
      month outcome. RESULTS: We found that admission monocyte count was not only a
      better predictor (AUC = 0.778; 95% confidence interval (CI), 0.679-0.858) of
      favourable outcomes (GOSE 5-8) at 6 months post-injury than were admission
      haemoglobin (AUC = 0.629; 95% CI, 0.522-0.728) and blood glucose (AUC = 0.616;
      95% CI, 0.508-0.716) levels for patients with moderate-to-severe TBI (GCS <= 12),
      but also an independent predictor of 6-month outcome (adjusted odds ratio, 1.35;
      95% CI, 1.10-1.65; p = 0.004). CONCLUSIONS: The present study suggests that an
      increase in admission monocyte count is correlated with a favourable 6-month
      outcome in patients with moderate-to-severe TBI.

PMID- 29355431
TI  - Risk factors and direct medical cost of early versus late unplanned readmissions
      among diabetes patients at a tertiary hospital in Singapore.
AB  - OBJECTIVE: To examine the risk factors and direct medical costs associated with
      early (<=30 days) versus late (31-180 days) unplanned readmissions among patients
      with type 2 diabetes in Singapore. METHODS: Risk factors and associated costs
      among diabetes patients were investigated using electronic medical records from a
      local tertiary care hospital from 2010 to 2012. Multivariable logistic regression
      was used to identify risk factors associated with early and late unplanned
      readmissions while a generalized linear model was used to estimate the direct
      medical cost. Sensitivity analysis was also performed. RESULTS: A total of 1729
      diabetes patients had unplanned readmissions within 180 days of an index
      discharge. Length of index stay (a marker of acute illness burden) was one of the
      risk factors associated with early unplanned readmission while patient behavior
      related factors, like diabetes-related medication adherence, were associated with
      late unplanned readmission. Adjusted mean cost of index admission was higher
      among patients with unplanned readmission. Sensitivity analysis yielded similar
      results. CONCLUSIONS: Existing routinely captured data can be used to develop
      prediction models that flag high risk patients during their index admission,
      potentially helping to support clinical decisions and prevent such readmissions.

PMID- 29355432
TI  - An update on the treatment of pediatric-onset Langerhans cell histiocytosis
      through pharmacotherapy.
AB  - INTRODUCTION: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasia
      driven by activation mutations alongside the MAPK pathway. Its broad spectrum of
      clinical manifestations and diverse course and clinical outcome, make
      interpretation of trial data difficult. Use of different stratification systems
      further complicates comparison among trials. Areas covered: This review
      summarizes the published data derived from prospective clinical trials from Phase
      II onwards. PubMed was searched using combinations of the keywords 'Langerhans
      cell histiocytosis', 'histiocytosis X', 'pediatric', 'children', 'treatment', and
      'therapy'. Only full-length papers published in English and German were included
      in the review. Expert opinion: Mortality in multisystem LCH is restricted to
      patients with involvement of risk organs (hematopoiesis, liver and spleen) at
      diagnosis, and is particularly high (up to 60-70%) if systemic therapy fails to
      control the disease. For the rest of the cohort, mortality is almost negligible,
      and the main challenges are disease relapses and related permanent consequences
      (encountered in up to 50% of the survivors). While systemic therapy has clearly
      improved survival of patients with most severe disease form, its role in
      providing sustained disease control and preventing permanent consequences in
      patients with 'low risk' disease is less clear.

PMID- 29355433
TI  - Store and forward Teledermatology - the Newport way.
AB  - Teledermatology plays a vital role within Aneurin Bevan University Health Board.
      Alongside Consultant Dermatologists we developed Teledermatology to meet clinical
      needs. This article illustrates the implementation process of the service,
      highlighting legal and ethical issues that were considered along with the success
      and scope of the service. The Teledermatology service rapidly reduced waiting
      times for patients and increased access to specialist care which is cost
      effective for the Health Board. Following successful implementation and increased
      demand, there is the scope for expansion. The service is developing additional
      Teledermatology clinics within the Health Board, evolving telemedicine.

PMID- 29355434
TI  - Ranting in 2018: Are We Making Progress?

PMID- 29355435
TI  - Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro
      Compared with Humalog Insulin Lispro in People with Diabetes.
AB  - BACKGROUND: SAR342434 (SAR-Lis) is a biosimilar (follow-on) of insulin lispro
      (Humalog(r); Ly-Lis). Two randomized, controlled, open-label, parallel-group,
      phase 3 studies were conducted to compare the efficacy and safety of SAR-Lis and
      Ly-Lis, both in combination with insulin glargine (Lantus(r)). SORELLA 1 was a 12
      month study in 507 people with type 1 diabetes mellitus (T1DM); SORELLA 2 was a 6
      month study in 505 people with type 2 diabetes mellitus (T2DM). In this study,
      the impact of anti-insulin antibodies (AIA) to SAR-Lis and Ly-Lis on safety and
      glycemic control is reported. METHODS: AIA were measured regularly throughout
      both studies at a centralized laboratory blinded to treatment groups using a drug
      specific AIA assay. The AIA status (positive or negative), AIA titers, and cross
      reactivity to human insulin, insulin glargine, and insulin glargine metabolite M1
      were analyzed. The potential effect of AIA on safety, particularly as related to
      hypersensitivity reactions, hypoglycemia, and treatment-emergent adverse events,
      as well as on glycemic control (HbA1c, insulin dose), was evaluated. RESULTS: AIA
      positive status at baseline was similar for the two insulins, but higher in T1DM
      than in T2DM. In both studies, the percentage of people newly developing AIA in
      the two treatment groups, or having a >=4-fold increase in AIA titers, did not
      differ. No relationship was observed between maximum individual AIA titers and
      change in HbA1c or insulin dose, hypoglycemia, or hypersensitivity reactions or
      between efficacy/safety measures and subgroups by presence or absence of
      treatment-emergent AIA. Hypersensitivity events and events adjudicated as
      allergic reactions were few and did not differ between the two groups.
      CONCLUSION: Insulin lispro SAR342434 and the originator insulin lispro had a
      similar immunogenicity profile in people with T1DM or T2DM.

PMID- 29355436
TI  - Can Biomarkers Help Target Maturity-Onset Diabetes of the Young Genetic Testing
      in Antibody-Negative Diabetes?
AB  - BACKGROUND: Maturity-onset diabetes of the young (MODY) is an antibody-negative,
      autosomal dominant form of diabetes. With the increasing prevalence of diabetes
      and the expense of MODY testing, markers to identify those who need further
      genetic testing would be beneficial. We investigated whether HLA genotypes,
      random C-peptide, and/or high-sensitivity C-reactive protein (hsCRP) levels could
      be helpful biomarkers for identifying MODY in antibody-negative diabetes.
      METHODS: Subjects (N = 97) with diabetes onset <=age 25, measurable C-peptide
      (>=0.1 ng/mL), and negative for all four diabetes autoantibodies were enrolled at
      a large academic center and tested for MODY 1-5 through Athena Diagnostics. A
      total of 22 subjects had a positive or very likely pathogenic mutation for MODY.
      RESULTS: Random C-peptide levels were significantly different between MODY
      positive and MODY-negative subjects (0.16 nmol/L vs. 0.02 nmol/L; P = 0.02).
      After adjusting for age and diabetes duration, hsCRP levels were significantly
      lower in MODY-positive subjects (0.37 mg/L vs. 0.87 mg/L; P = 0.02). Random C
      peptide level >=0.15 nmol/L obtained at >=6 months after diagnosis had 83%
      sensitivity for diagnosis of MODY with a negative predictive value of 96%.
      Receiver operating characteristic curves showed that area under the curve for
      random C-peptide (0.75) was significantly better than hsCRP (0.54), high-risk HLA
      DR3/4-DQB1*0302 (0.59), and high-risk HLA/random C-peptide combined (0.54; P =
      0.03). CONCLUSIONS: Random C-peptide obtained at >=6 months after diagnosis can
      be a useful biomarker to identify antibody-negative individuals who need further
      genetic testing for MODY, whereas hsCRP and HLA do not appear to improve this
      antibody/C-peptide-based approach.

PMID- 29355437
TI  - Continuous Glucose Monitoring in Healthy Children Aged 2-8 Years.
AB  - BACKGROUND: The purpose of this study was to add the missing information on
      glycemic levels and patterns as measured by continuous glucose monitoring (CGM)
      in the daily life of healthy children aged 2-8 years. These data are needed when
      studying glycemic patterns and treatment outcome in children aged 2-8 years with
      diabetes. METHODS: Each of the 15 healthy children aged 2-7.99 years used a CGM
      device (Dexcom G4 Platinum) for 7 days. RESULTS: A total of 15 children (10
      girls) aged 5.4 +/- 1.6 years registered a mean of 1976 +/- 15 counts. Mean
      sensor glucose was 5.3 +/- 1.0 mmol/L (95 +/- 18 mg/dL) and 89% of values were in
      the range 4-7.8 mmol/L (72-140 mg/dL), 9% of sensor glucose values were <4.0
      mmol/L (72 mg/dL), and 2% of sensor glucose values were >7.8 mmol/L (140 mg/dL).
      CONCLUSION: We present glycemic data as measured by CGM in healthy children aged
      2-8 years.

PMID- 29355438
TI  - Insulin Sensitivity Index-Based Optimization of Insulin to Carbohydrate Ratio: In
      Silico Study Shows Efficacious Protection Against Hypoglycemic Events Caused by
      Suboptimal Therapy.
AB  - BACKGROUND AND AIM: The insulin to carbohydrate ratio (CR) is a parameter used by
      patients with type 1 diabetes (T1D) to calculate the premeal insulin bolus.
      Usually, it is estimated by the physician based on patient diary, but modern
      diabetes technologies, such as subcutaneous glucose sensing (continuous glucose
      monitoring, CGM) and insulin delivery (continuous subcutaneous insulin infusion,
      CSII) systems, can provide important information for its optimization. In this
      study, a method for CR optimization based on CGM and CSII data is presented and
      its efficacy and robustness tested in several in silico scenarios, with the
      primary aim of increasing protection against hypoglycemia. METHODS: The method is
      based on a validated index of insulin sensitivity calculated from sensor and pump
      data (SISP), area under CGM and CSII curves. The efficacy and robustness of the
      method are tested in silico using the University of Virginia/Padova T1D
      simulator, in several suboptimal therapy scenarios: with nominal CR variation,
      over/underestimation of meal size or suboptimal basal insulin infusion. Simulated
      CGM and CSII data were used to calculate the optimal CR. The same scenarios were
      then repeated using the estimated CR and glycemic control was compared. RESULTS:
      The optimized CR was efficacious in protecting against hypoglycemic events caused
      by suboptimal therapy. The method was also robust to possible error in
      carbohydrate count and suboptimal basal insulin infusion. CONCLUSIONS: A novel
      method for CR optimization in T1D, implementable in daily life using CGM and CSII
      data, is proposed. The method can be used both in open- and closed-loop insulin
      therapy.

PMID- 29355440
TI  - Optimizing the Estimation of Carbohydrate-to-Insulin Ratio and Correction Factor.

PMID- 29355439
TI  - Design and Clinical Evaluation of a Novel Low-Glucose Prediction Algorithm with
      Mini-Dose Stable Glucagon Delivery in Post-Bariatric Hypoglycemia.
AB  - BACKGROUND: Postbariatric hypoglycemia (PBH) is a complication of bariatric
      surgery with limited therapeutic options. We developed an event-based system to
      predict and detect hypoglycemia based on continuous glucose monitor (CGM) data
      and recommend delivery of minidose liquid glucagon. METHODS: We performed an
      iterative development clinical study employing a novel glucagon delivery system:
      a Dexcom CGM connected to a Windows tablet running a hypoglycemia prediction
      algorithm and an Omnipod pump filled with an investigational stable liquid
      glucagon formulation. Meal tolerance testing was performed in seven participants
      with PBH and history of neuroglycopenia. Glucagon was administered when
      hypoglycemia was predicted. Primary outcome measures included the safety and
      feasibility of this system to predict and prevent severe hypoglycemia. Secondary
      outcomes included hypoglycemia prediction by the prediction algorithm,
      minimization of time below hypoglycemia threshold using glucagon, and prevention
      of rebound hyperglycemia. RESULTS: The hypoglycemia prediction algorithm alerted
      for impending hypoglycemia in the postmeal state, prompting delivery of glucagon
      (150 MUg). After observations of initial incomplete efficacy to prevent
      hypoglycemia in the first two participants, system modifications were
      implemented: addition of PBH-specific detection algorithm, increased glucagon
      dose (300 MUg), and a second glucagon dose if needed. These modifications,
      together with rescue carbohydrates provided to some participants, contributed to
      progressive improvements in glucose time above the hypoglycemia threshold (75
      mg/dL). CONCLUSIONS: Preliminary results indicate that our event-based automatic
      monitoring algorithm successfully predicted likely hypoglycemia. Minidose
      glucagon therapy was well tolerated, without prolonged or severe hypoglycemia,
      and without rebound hyperglycemia.

PMID- 29355442
TI  - Editorial.

PMID- 29355441
TI  - NTproBNP and ST2 as predictors for all-cause and cardiovascular mortality in
      elderly patients with symptoms suggestive for heart failure.
AB  - BACKGROUND: A new biomarker, suppression of tumorigenicity 2 (ST2) has been
      introduced as a marker for fibrosis and hypertrophy. Its clinical value in
      comparison with N-terminal pro-hormone of brain natriuretic peptide /Amino
      terminal pro-B-type natriuretic peptide (NTproBNP) in predicting mortality in
      elderly patients with symptoms of heart failure (HF) is still unclear. AIM: To
      evaluate the prognostic value for all-cause- and cardiovascular mortality of ST2
      or NTproBNP and the combination of these biomarkers. PATIENTS AND METHODS: One
      hundred seventy patients patients with clinical symptoms of HF (77 (45%) were
      with verified HF) were recruited from one selected primary health care center
      (PHC) in Sweden and echocardiography was performed in all patients. Blood samples
      were obtained from 159 patients and stored frozen at -70  degrees C. NTproBNP was
      analyzed at a central core laboratory using a clinically available
      immunoassay.ST2 was analyzed with Critical Diagnostics Presage ST2 ELISA
      immunoassay. RESULTS: We studied 159 patients (mean age 77 +/- 8.3 years, 70%
      women). During ten years of follow up 78 patients had died, out of which 50
      deaths were for cardiovascular reasons. Continuous NTproBNP and ST2 were both
      significantly associated with all-cause mortality (1.0001; 1.00001-1.0002, p =
      0.04 and 1.03; 1.003-1.06, p = 0.03), NTproBNP but not ST2 remained significant
      for cardiovascular mortality after adjustments (1.0001; 1.00001-1.0002, p = 0.03
      and 1.01; 0.77-1.06, p = 0.53), respectively. NTproBNP above median (>328 ng/L)
      compared to below median was significantly associated with all-cause
      mortality(HR: 4.0; CI :2.46-6.61; p < 0.001) and cardiovascular mortality (HR:
      6.1; CI: 3.11-11.95; p < 0.001). Corresponding analysis for ST2 above median
      (25.6 ng/L) was not significantly associated neither with all-cause mortality
      (HR; 1.4; CI: 0.89-2.77) nor cardiovascular mortality (HR: 1.3; CI: 0.73-2.23)
      and no significant interaction of NTproBNP and ST2 (OR: 1.1; CI: 0.42-3.12) was
      found. CONCLUSION: In elderly patients with symptoms of heart failure ST2 was not
      superior to NTproBNP to predict all cause or cardiovascular mortality.
      Furthermore, it is unclear if the combination of ST2 and NTproBNP will improve
      long-term prognostication beyond what is achieved by NTproBNP alone.

PMID- 29355443
TI  - Downstream processing of lactoperoxidase from milk whey by involving liquid
      emulsion membrane.
AB  - The current work deals with downstream processing of lactoperoxidase using liquid
      emulsion membrane from the bovine milk whey, which is a by-product from dairy
      industry. It is an alternate separation technique that can be used for the
      selective extraction of lactoperoxidase. The extraction of lactoperoxidase in
      liquid emulsion membrane takes place due to the electrostatic interaction between
      the enzyme and polar head group of reverse micellar surfactant. The optimum
      conditions resulted in 2.86 factor purity and activity recovery of 75.21%.
      Downstream processing involving liquid emulsion membrane is a potential technique
      for the extraction of lactoperoxidase from bovine whey.

PMID- 29355444
TI  - Patient injury claims involving fractures of the distal radius.
AB  - Background and purpose - Optimal treatment for distal radius fractures remains
      controversial, with a significant number of fractures resulting in complications
      and long-term morbidity. We investigated patient injury claims related to distal
      radius fractures to detect the critical steps in the treatment leading to
      avoidable adverse events Patients and methods - We analyzed all compensated
      patient injury claims in Finland between 2007 and 2011. Claims were collected
      from the Patient Insurance Center's (PIC) nationwide claim register. Patients of
      all ages were included. Each claim decision, original patient records, and
      radiographs related to treatment were reviewed. Results - During the study
      period, the PIC received 584 claims regarding distal radius fractures, of which
      208 (36%) were compensated. Pain and impaired wrist function were the most common
      subjective reasons to file claims among compensated patients. In 66/208 patients,
      more than 1 adverse event leading to patient injury was detected. The detected
      adverse events could be divided into 3 main groups: diagnostic errors (36%, n =
      103), decision/planning errors (30%, n = 87), and insufficient technical
      execution (32%, n = 91). Issues related to malalignment were the main concerns in
      each group. Diagnostic errors were often related to incorrect assessment of the
      fracture (re)displacement (75%, n = 78). All of the decision-making errors
      concerned physicians' decisions to accept unsatisfactory fracture alignment. The
      most common technical error was insufficient reduction (29%, n = 26).
      Interpretation - We identified avoidable adverse events behind patient injuries
      related to distal radius fracture treatment. This study will help physicians to
      recognize the critical steps in the treatment of this common fracture and enhance
      patient safety.

PMID- 29355446
TI  - Negotiating the humanitarian space: new opportunities for action and research.

PMID- 29355445
TI  - Intramolecular crosstalk between catalytic activities of receptor kinases.
AB  - Signal modulation is important for the growth and development of plants and this
      process is mediated by a number of factors including physiological growth
      regulators and their associated signal transduction pathways. Protein kinases
      play a central role in signaling, including those involving pathogen response
      mechanisms. We previously demonstrated an active guanylate cyclase (GC) catalytic
      center in the brassinosteroid insensitive receptor (AtBRI1) within an active
      intracellular kinase domain resulting in dual enzymatic activity. Here we propose
      a novel type of receptor architecture that is characterized by a functional GC
      catalytic center nested in the cytosolic kinase domain enabling intramolecular
      crosstalk. This may be through a cGMP-AtBRI1 complex forming that may induce a
      negative feedback mechanism leading to desensitisation of the receptor, regulated
      through the cGMP production pathway. We further argue that the comparatively low
      but highly localized cGMP generated by the GC in response to a ligand is
      sufficient to modulate the kinase activity. This type of receptor therefore
      provides a molecular switch that directly and/or indirectly affects ligand
      dependent phosphorylation of downstream signaling cascades and suggests that
      subsequent signal transduction and modulation works in conjunction with the
      kinase in downstream signaling.

PMID- 29355447
TI  - Enhanced recovery programmes in thoracic surgery: how does the future look?

PMID- 29355448
TI  - Seven-day access to NHS primary care: how does England compare with Europe?

PMID- 29355449
TI  - Cigarette smoking and cerebral blood flow in a cohort of middle-aged adults.
AB  - Cigarette smoking is often associated with dementia. This association is thought
      to be mediated by hypoperfusion; however, how smoking behavior relates to
      cerebral blood flow (CBF) remains unclear. Using data from the Coronary Artery
      Risk Development in Young Adults (CARDIA) cohort (mean age = 50; n = 522), we
      examined the association between smoking behavior (status, cumulative pack-years,
      age at smoking initiation, and years since cessation) and CBF (arterial spin
      labeling) in brain lobes and regions linked to dementia. We used adjusted linear
      regression models and tested whether associations differed between current and
      former-smokers. Compared to never-smokers, former-smokers had lower CBF in the
      parietal and occipital lobes, cuneus, precuneus, putamen, and insula; in
      contrast, current-smokers did not have lower CBF. The relationship between pack
      years and CBF was different between current and former-smokers ( p for
      interaction < 0.05): Among current-smokers, higher pack-years were associated
      with higher occipital, temporal, cuneus, putamen, insula, hippocampus, and
      caudate CBF; former-smokers had lower caudate CBF with increasing pack-years.
      Results show links between smoking and CBF at middle-age in regions implicated in
      cognitive and compulsive/addictive processes. Differences between current and
      former smoking suggest that distinct pathological and/or compensatory mechanisms
      may be involved depending on the timing and history of smoking exposure.

PMID- 29355450
TI  - Dual composite reference standards (dCRS) in molecular diagnostic research: A new
      approach to reduce bias in the presence of Imperfect reference.
AB  - A main challenge in molecular diagnostic research is to accurately evaluate the
      performance of a new nucleic acid amplification test when the reference standard
      is imperfect. Several approaches, such as discrepant analysis, composite
      reference standard (CRS) method, or latent class analysis (LCA), are commonly
      applied for this purpose by combining multiple imperfect (reference) test
      results. In discrepant analysis or LCA, test results from the new assay are often
      involved in the construction of a new pseudo-reference standard, which results in
      the potential risk of overestimating the parameters of interest. On the contrary,
      the CRS methods only combine the results of reference tests, which is more
      preferable in practice. In this article, we study the properties of two extreme
      CRS methods, i.e., combining multiple reference test results by the "any
      positive" rule or by the "all-positive" rule, and propose a new approach "dual
      composite reference standards (dCRS)" based on these two extreme methods to
      reduce the biases of the estimates. Simulations are performed for various
      scenarios and the proposed approach is applied to two real datasets. The results
      demonstrate that our approach outperforms other commonly used approaches and
      therefore is recommended for future applications.

PMID- 29355451
TI  - Slowly progressive behavioral frontotemporal dementia with C9orf72 mutation. Case
      report and review of the literature.
AB  - We present a 86-year-old woman without relevant medical history and two brothers
      who died by dementia, who started at 55 years with depression and personality
      changes with ongoing worsening (>30 years) and functional decline. Screening
      dementia blood test and brain magnetic resonance imaging did not show results
      that pointed to a secondary cause. The patient met the diagnostic criteria for
      possible behavioral frontotemporal dementia with a slow progression (bvFTD-SP),
      suggesting a benign variant. A genetic study confirmed a C9ORF72 hexanucleotide
      expansion, making this the sixth case mentioned in the literature. We review and
      discuss the other cases described previously.

PMID- 29355452
TI  - Retrospective study of paraneoplastic neurological syndromes in a Chinese Han
      population from Shandong, East China.
AB  - OBJECTIVE: To analyze the clinical features, diagnostic strategies and
      therapeutic methods associated with paraneoplastic neurological syndromes.
      METHODS: A retrospective study of paraneoplastic neurological syndromes was
      performed at a single center in Shandong, East China. The medical records and
      follow-up data of 28 patients were intensively reviewed between February 2011 and
      December 2014. RESULTS: Twenty-four (85.7%) patients experienced subacute or
      chronic onset of disease, and the most common symptoms reported were mild
      myasthenia and paresthesias. Twenty-five (89.3%) patients presented nervous
      system lesions prior to occult tumors, and the median time frame between
      paraneoplastic neurological syndromes onset and the diagnosis of a tumor was 15
      weeks. Sensorimotor neuropathy, Lambert-Eaton myasthenic syndrome and limbic
      encephalitis were the three most common neurological syndromes reported. Elevated
      serum tumor markers were observed in 44.0% of patients, while 40.7% of patients
      were positive for onconeural antibodies. Tumors were detected in 21 (75.0%)
      patients after repeated whole-body screening, and lung carcinomas were the most
      common primary tumor detected. Seventeen patients received anti-tumor or
      immunological therapy, and clinical symptoms were relieved in 13 (76.5%) of these
      patients. CONCLUSIONS: In the majority of paraneoplastic neurological syndromes
      patients, the onset of disease is subacute or chronic with mild clinical
      symptoms. Nervous system lesions usually occur prior to occult tumors with
      complicated and various clinical manifestations. Neither tumor markers nor
      onconeural antibodies exhibit a high rate of occurrence, while repeated whole
      body screening is helpful in identifying occult tumors. Early diagnosis and
      treatment are crucial to these patients.

PMID- 29355453
TI  - Critical factors affecting ethanol production by immobilized Pichia stipitis
      using corn cob hemicellulosic hydrolysate.
AB  - Fermentation of xylose from hydrolysate of acid-treated corn cob by Pichia
      stipitis is inhibited by acetic acid and lignin derivatives. In the present
      study, we have designed and implemented an immobilized cell culture for xylose to
      ethanol conversion from acid-treated corn cob hydrolysate without the removal of
      fermentation inhibitors. In this study, cultivations of suspended and immobilized
      Pichia were compared in terms of ethanol yield and productivity to investigate
      whether the cell immobilization could improve resistance to inhibitors. Cell
      immobilization clearly favored the fermentative metabolism in nondetoxified corn
      cob hydrolysate leading to an improvement of twofold ethanol productivity as
      compared to that achieved with suspension culture. Calcium alginate as an
      immobilization matrix was selected to immobilize Pichia cells. Concentrations of
      sodium alginate, calcium chloride, and fermentor agitation speed were optimized
      for ethanol production using statistical method. Statistical analysis showed that
      agitation speed had maximum influence on ethanol production by immobilized Pichia
      cells. In comparison to suspension culture, immobilization had a positive impact
      on the fermentative metabolism of Pichia, improving the ethanol yield from 0.40
      to 0.43 g/g and productivity from 0.31 to 0.51 g/L/h for acid-treated corn cob
      hydrolysate.

PMID- 29355454
TI  - Optimization of simultaneously enzymatic fructo- and inulo-oligosaccharide
      production using co-substrates of sucrose and inulin from Jerusalem artichoke.
AB  - Prebiotic substances are extracted from various plant materials or enzymatic
      hydrolysis of different substrates. The production of fructo-oligosaccharide
      (FOS) and inulo-oligosaccharide (IOS) was performed by applying two substrates,
      sucrose and inulin; oligosaccharide yields were maximized using central composite
      design to evaluate the parameters influencing oligosaccharide production. Inulin
      from Jerusalem artichoke (5-15% w/v), sucrose (50-70% w/v), and inulinase from
      Aspergillus niger (2-7 U/g) were used as variable parameters for optimization.
      Based on our results, the application of sucrose and inulin as co-substrates for
      oligosaccharide production through inulinase hydrolysis and synthesis is viable
      in comparative to a method using a single substrate. Maximum yields (674.82 mg/g
      substrate) were obtained with 5.95% of inulin, 59.87% of sucrose, and 5.68 U/g of
      inulinase, with an incubation period of 9 hr. The use of sucrose and inulin as co
      substrates in the reaction simultaneously produced FOS and IOS from sucrose and
      inulin. Total conversion yield was approximately 67%. Our results support the
      high value-added production of oligosaccharides using Jerusalem artichoke, which
      is generally used as a substrate in prebiotics and/or bioethanol production.

PMID- 29355455
TI  - Biologic therapies to enhance intervertebral disc repair.
AB  - Degenerative disc disease is a progressive, chronic disorder with strong
      association to pain, where the dysregulated tissue environment signals disc
      cells, thereby leading to a low inflammatory process and slow extracellular
      matrix degradation and fibrosis in a perpetual vicious cycle, generating a
      structural and functional failure of intervertebral disc joint (IVDJ). Among
      current biologic therapies, there is an emerging minimally invasive strategy that
      consists of infiltrating plasma rich in growth factors, a safe and efficacious
      therapeutic approach for other musculoskeletal degenerative conditions. This
      review summarizes the homeostasis and degeneration of IVDJ, discusses some
      results on basic science and therapeutic use of platelet-rich plasma products and
      advances an alternative minimally invasive biologic therapy in IVDJ degeneration
      and chronic back pain.

PMID- 29355457
TI  - Curtailed two-stage design for comparing two arms in randomized phase II clinical
      trials.
AB  - In phase II clinical trials, patients are recruited sequentially and consequently
      the time required to complete the clinical trial will become long if the accrual
      rate is low. To speed up the drug development process and account for ethical
      issues, stochastically and non-stochastically curtailed two-stage designs have
      been proposed in single-arm phase II clinical trials. More recently, randomized
      phase II clinical trials are being increasingly recommended to avoid biased
      evaluation of the treatment effect when compared with a historical control. The
      current patient population and the historical one may be quite heterogeneous.
      Moreover, it is impossible to randomly assign patients for treatments.
      Consequently, various two-stage designs have been presented for comparing two
      arms. Since the sample size required in a randomized phase II trial is usually
      larger than that required in a single-arm phase II trial, we introduce the
      concept of curtailed sampling procedure to develop curtailed two-stage design for
      two-armed, randomized phase II clinical trials. The proposed design does not
      require pairwise patient response comparison, yet it allows a trial to be stopped
      early as soon as the difference in therapeutic effect of the experimental therapy
      and the standard at the end of a trial is foreknown.

PMID- 29355456
TI  - Icariin improves Fanconi anemia hematopoietic stem cell function through SIRT6
      mediated NF-kappa B inhibition.
AB  - Icariin (ICA) is a flavonoid glucoside derived from the Epimedium plant genus,
      which has potent regenerative properties and is used in western medicine to treat
      impotence. Recently, ICA has generated great interest in improving hepatic
      stellate cell function and cardiac rejuvenation. However, how this natural
      component functions in hematopoiesis remains unexplored. Here we have examined
      the role of ICA on hematopoietic stem cells (HSCs) using the cancer-prone disease
      model of Fanconi anemia (FA), an inherited bone marrow failure syndrome with
      extremely high risk of leukemic predisposition. We show that ICA reverses the
      less quiescent status of HSCs deficient for the Fanca or Fancd2 gene, and
      improves the ability of these mutant stem cells to form colony formation units
      (CFU) in vitro and reconstitutes hematopoiesis in transplanted recipients.
      Further analysis reveals that ICA upregulates enzyme activity of the chromatin
      binding protein SIRT6 in Fanca-/- and Fancd2-/- HSCs, both of which have an
      intrinsic low SIRT6 activity. Furthermore, forced expression of SIRT6 blocks the
      natural decline of quiescent HSCs in Fanca-/- or Fancd2-/- mice and improves the
      repopulating capacity of these mutant HSCs in irradiated recipients.
      Mechanistically, ICA enhances SIRT6-mediated H3K9 deacetylation on the promoter
      of NF-kappaB and represses the expression of NF-kappaB target genes. Together,
      our findings indicate that ICA improves the function of HSCs by stimulating SIRT6
      activity and contributes to the regenerative effect of ICA.

PMID- 29355458
TI  - Protein a resin lifetime study: Evaluation of protein a resin performance with a
      model-based approach in continuous capture.
AB  - A modified shrinking core model (MSCM) has been used to describe the mechanism
      for the degradation of Protein A resin particles taking place under continuous
      chromatographic operation. The model is based on the hypothetical shrinkage of
      the boundary layer of the resin particles, which house the active Protein A
      ligands within their pores. The caustic during the sanitization phase of
      chromatography has been determined to cause the Protein A ligand degradation.
      Protein A resins provided by manufacturers possess unique caustic stability,
      which has been used in MSCM to appraise the ligand degradation. The kinetic model
      utilized semiempirical parameters including diffusion constant, rate constant,
      stoichiometric factor, and reaction order. The parameters were estimated from
      column breakthrough experiments to simulate continuous Protein A chromatography
      for three distinct resins. The reaction order has been identified as the key
      parameter for predicting the degradation kinetics. The recorded reaction orders
      vary for three different resins with the resin B showing the highest reaction
      order of 4 and lowest being 1.65 for the resin C. The model can predict the
      effects of caustic on resin performance and displayed that minimal degradation of
      the resins A and B occurred, when exposed to 0.1 N and 0.2N NaOH, retaining up to
      96% binding capacity after 240 cycles. The adsorption study conducted for the
      resin B demonstrated the dynamic physical and chemical changes transpiring
      through the life cycle of the resin, further supported the degradation model. The
      performance data demonstrate that the resin B exhibits the desirable performance,
      with higher reaction order indicating slower resin degradation, higher binding
      capacities, and increased sustenance of this binding capacity for extended
      duration. The degradation model can be extended to build effective cleaning
      strategies for continuous downstream processing.

PMID- 29355459
TI  - Enhancement of erythritol production by Trichosporonoides oedocephalis ATCC 16958
      through regulating key enzyme activity and the NADPH/NADP ratio with metal ion
      supplementation.
AB  - Erythritol, a well-known natural sweetener, is mainly produced by microbial
      fermentation. Various metal ions (Al3+, Cu2+, Mn2+, and Ni2+) were added to the
      culture medium of Trichosporonoides oedocephalis ATCC 16958 at 30 mg/L in shake
      flask cultures. Compared with controls, Cu2+ increased the erythritol content by
      86% and decreased the glycerol by-product by 31%. After 48 hr of shake flask
      culture, sodium dodecyl sulfate polyacrylamide gel electrophoresis showed that
      expression levels of erythrose reductase (ER) in the presence of 30 mg/L CuSO4 .
      5H2O were higher than those obtained after treatment with other examined metal
      ions. Furthermore, after 108 hr of batch culture in a 5-L bioreactor,
      supplementation with 30 mg/L of CuSO4 . 5H2O increased the specific erythritol
      content by 27%. Further studies demonstrated that ER activity under 30 mg/L CuSO4
      . 5H2O supplementation in a fermentor was overtly increased compared with the
      control after 60 hr, while glycerol-3-phosphate dehydrogenase activity was
      clearly reduced in most of the fermentation process. Furthermore, the NADPH/NADP
      ratio was slightly lower in T. oedocephalis cells treated with Cu2+ compared with
      control cells. These results provide further insights into Cu2+ effects on
      erythritol biosynthesis in T. oedocephalis and should improve the industrial
      production of erythritol by biological processes.

PMID- 29355460
TI  - Infantile intrathoracic large airway obstruction in a setting with a high
      prevalence of tuberculosis/HIV.
AB  - Background There has been no detailed analysis of the cause of intrathoracic
      large airway obstruction in infants in a resource-limited environment with a high
      prevalence of pulmonary tuberculosis (PTB) and human immunodeficiency virus
      (HIV). Aim To define the aetiology and severity of intrathoracic large airway
      obstruction in infants in a tertiary South African hospital with a high
      prevalence of PTB and HIV. Methods A retrospective study of infants was conducted
      with computerised tomography (CT) evidence of intrathoracic large airway
      obstruction from 1 January 2011 to 31 May 2014. CT scans were evaluated for the
      cause, site and severity of airway narrowing, with severity stratified as 'mild'
      (<50%), 'moderate' (51-75%) or 'severe' (>75%). Results Forty-four patients (28
      males, 64%; median age 145 days, range 5-331), and 79 sites of attenuation were
      included. Vascular (22/44, 50%) and nodal (18/44, 41%) compressions accounted for
      over 90% of cases. Thirty-five patients (79.5%) had at least one site of
      moderate/severe attenuation, and 26 (59%) had multiple such sites. Adenopathy was
      the commonest cause of moderate/severe compression (18/35, 51%). All cases of
      nodal compression were of tuberculous origin. HIV-serology was recorded in 32
      patients (73%), one of whom, with vascular compression, was HIV-infected. Half of
      the patients (11/22, 50%) with vascular compression had congenital abnormalities,
      most commonly cardiac anomalies (7/22, 32%). There were no synchronous vascular
      and nodal compressions. Conclusion Infantile intrathoracic large airway
      obstruction where there is a high prevalence of PTB and HIV is characterised by
      its extrinsic aetiology, severity and multicentricity, with more than half of all
      moderate/severe obstructions being caused by tuberculous adenopathy.

PMID- 29355461
TI  - Temperature gradient-based high-cell density fed-batch fermentation for the
      production of pyruvate oxidase by recombinant E. coli.
AB  - Pyruvate oxidase (PyOD) is a very powerful enzyme for clinical diagnostic
      applications and environmental monitoring. Influences of temperature on cell
      growth, plasmid stability, and PyOD expression during the PyOD fermentation
      process by recombinant Escherichia coli were investigated. Based on the
      influences of temperature on the physiological metabolism, a novel high-cell
      density fed-batch cultivation with gradient temperature decrease strategy for
      effective PyOD production was achieved, under which the biomass (OD600) of
      recombinant E. coli could reach to 71 and the highest PyOD activity in broth
      could reach to 3,307 U/L in 26 hr fermentation.

PMID- 29355462
TI  - Immunotherapy approach with recombinant survivin adjuvanted with alum and MIP
      suppresses tumor growth in murine model of breast cancer.
AB  - Survivin has received attention as a potential target for cancer immunotherapy
      because of its crucial role in oncogenesis. We undertook this study to evaluate
      the immunotherapeutic potential of combination of recombinant survivin along with
      adjuvant alum and immune modulator Mycobacterium indicus pranii (MIP). In vivo
      efficacy of the combination was studied in an invasive murine breast cancer
      model. Recombinant survivin protein was purified from Escherichia coli based
      expression system and characterized by western blotting. Purified survivin
      protein was combined with alum and MIP and was used for immunization of Balb/c
      mice. Antigen-primed animals were then challenged with syngeneic mammary tumor
      cells known as 4T-1. Balb/c mice spontaneously develop tumor when inoculated with
      4T-1 cells. Antigen and adjuvant combination was immunogenic and significantly
      suppressed tumor growth in mice immunized with combination of recombinant
      survivin (10 ug), alum, and MIP. This is the first report that describes a
      combination immunotherapy approach using recombinant survivin, alum, and MIP in
      highly metastatic murine breast cancer model and holds promise for development of
      new biotherapeutics for cancer.

PMID- 29355463
TI  - Effects of radiation response modifiers given after lethal whole-abdominal
      irradiation.
AB  - PURPOSE: Although radiation is used to treat cancer and generate electricity,
      radiotherapy-induced complications and nuclear disasters are issues of great
      concern. The small bowel and bone marrow are the two major organs injured by
      radiation, especially that from nuclear disasters. The development of effective
      drugs to alleviate radiation injuries is very important. We tested potential
      radiation response modifiers given after irradiation to alleviate radiation
      injuries and mortality. MATERIALS AND METHODS: Xenografts of C33A tumor cells
      with or without galectin-1 expression were implanted in SCID mice. Local tumor
      irradiation (6 Gy) was used to study radiosensitivity. The rate and time of tumor
      growth to 2 cm were observed using the Kaplan-Meier method. C57BL/6N mice were
      used to study the effects of whole-abdominal or whole-body irradiation. Drug
      administration was as follows: (1) vehicle; (2) interleukin 6 (IL-6) (50 ng/day);
      (3) anginex (10 mg/kg/day) (galectin-1 antagonist); or (4) flagellin (0.2 mg/kg)
      (Toll-like receptor 5 agonist). These treatments were compared for tumor size and
      survival time. RESULTS: The median time of tumor growth delay after 6 Gy
      irradiation was one week in tumors without galectin-1 expression, regardless of
      anginex administration. Anginex did not prolong the survival time after 18 Gy
      whole-abdominal irradiation. Flagellin did not prolong survival time after 18 Gy
      whole-abdominal irradiation. IL-6 prolonged the survival time after 18 Gy whole
      abdominal irradiation, with 5% survival. This was the best result in treating
      lethal 18 Gy whole-abdominal irradiation. Other than IL-6, no drugs decreased the
      survival rate after 7.5 Gy whole-body irradiation. CONCLUSIONS: Anginex has no
      protective effects against radiation injury and no radiosensitized effects on
      tumors. IL-6 is a potential agent for treating radiation-induced lethal injuries
      to the small bowel. However, it is not suitable for treating bone marrow damage
      after whole-body irradiation.

PMID- 29355464
TI  - Verification testing to confirm VO2max attainment in persons with spinal cord
      injury.
AB  - CONTEXT/OBJECTIVE: Maximal oxygen uptake (VO2max) is a widely used measure of
      cardiorespiratory fitness, aerobic function, and overall health risk. Although
      VO2max has been measured for almost 100 yr, no standardized criteria exist to
      verify VO2max attainment. Studies document that incidence of 'true' VO2max
      obtained from incremental exercise (INC) can be confirmed using a subsequent
      verification test (VER). In this study, we examined efficacy of VER in persons
      with spinal cord injury (SCI). DESIGN: Repeated measures, within-subjects study.
      SETTING: University laboratory in San Diego, CA. PARTICIPANTS: Ten individuals
      (age and injury duration = 33.3 +/- 10.5 yr and 6.8 +/- 6.2 yr) with SCI and 10
      able-bodied (AB) individuals (age = 24.1 +/- 7.4 yr). INTERVENTIONS: Peak oxygen
      uptake (VO2peak) was determined during INC on an arm ergometer followed by VER at
      105 percent of peak power output (% PPO). OUTCOME MEASURES: Gas exchange data,
      heart rate (HR), and blood lactate concentration (BLa) were measured during
      exercise. RESULTS: Across all participants, VO2peak was highly related between
      protocols (ICC = 0.98) and the mean difference was equal to 0.08 +/- 0.11 L/min.
      Compared to INC, VO2peak from VER was not different in SCI (1.30 +/- 0.45 L/min
      vs. 1.31 +/- 0.43 L/min) but higher in AB (1.63 +/- 0.40 L/min vs. 1.76 +/- 0.40
      L/min). CONCLUSION: Data show similar VO2peak between incremental and
      verification tests in SCI, suggesting that VER confirms VO2max attainment.
      However, in AB participants completing arm ergometry, VER is essential to
      validate appearance of 'true' VO2peak.

PMID- 29355466
TI  - The aesthetics of verticality: A gravitational contribution to aesthetic
      preference.
AB  - Verticality plays a fundamental role in the arts, portraying concepts such as
      power, grandeur, or even morality; however, it is unclear whether people have an
      aesthetic preference for vertical stimuli. The perception of verticality occurs
      by integrating vestibular-gravitational input with proprioceptive signals about
      body posture. Thus, these signals may influence the preference for verticality.
      Here, we show that people have a genuine aesthetic preference for stimuli aligned
      with the vertical, and this preference depends on the position of the body
      relative to the gravitational direction. Observers rated the attractiveness of
      lines that varied in inclination. Perfectly vertical lines were judged to be more
      attractive than those inclined clockwise or anticlockwise only when participants
      held an upright posture. Critically, this preference was not present when their
      body was tilted away from the gravitational vertical. Our results showed that
      gravitational signals make a contribution to the perception of attractiveness of
      environmental objects.

PMID- 29355468
TI  - Executive processes and timing: Comparing timing with and without reference
      memory.
AB  - Temporal perception is influenced by executive function. However, performance on
      different temporal tasks is often associated with different executive functions.
      This study examined whether using reference memory during a task influenced how
      performance was associated with executive resources. Participants completed
      temporal generalisation and bisection tasks, in their normal versions involving
      reference memory and in episodic versions without reference memory. Each timing
      task had two difficulty levels: easy and hard. Correlations between performance
      on these tasks and measures of executive function (updating, inhibition, task
      switching, and access to semantic memory) were assessed. Accuracy on the temporal
      generalisation task was correlated with memory access for all versions of the
      task. Updating correlated with accuracy only for the reference memory-based
      version of the task. Temporal bisection performance presented a different pattern
      of correlations. The bisection point was negatively correlated with inhibition
      scores, except for the easy episodic condition. The Weber ratio, considered a
      measure of temporal sensitivity, was negatively correlated with memory access
      only in the hard episodic condition. Together, the findings suggest that previous
      models of generalisation and bisection may not accurately reflect the underlying
      cognitive processes involved in the tasks.

PMID- 29355465
TI  - Predictors of readmission to acute care during inpatient rehabilitation for non
      traumatic spinal cord injury.
AB  - OBJECTIVES: To investigate the frequency of and reasons for readmissions to acute
      care (RTAC) during inpatient rehabilitation (IPR) after non-traumatic spinal cord
      injury (NT-SCI). To develop a predictive model for RTAC using identified risk
      factors. DESIGN: Retrospective case-control. SETTING: Academic IPR hospital.
      PARTICIPANTS: Individuals with NT-SCI admitted to an academic SCI rehabilitation
      unit from January 2014-December 2015. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Readmissions to acute care services from IPR. RESULTS: Thirty-seven
      participants (20%) experienced a RTAC for a total of 39 episodes. Thirty-five
      experienced 1 RTAC, while two had 2. The most common medical reasons for RTAC
      were infection (27%), neurological (27%), and noninfectious respiratory (16%).
      Multivariable logistic regression was used to develop a model to predict RTAC.
      Paraplegia was associated with 3.2 times increase in the odds of RTAC (P = 0.03).
      For every unit increase in FIM-Motor, there was a 5% reduction in the odds of
      RTAC (P = 0.03) Body mass index less than 30 decreased odds of RTAC by 61% (P =
      0.004). CONCLUSION: RTACs were associated with body mass index greater than 30,
      decreased FIM-Motor subscore on admission, and paraplegia. Physiatrists caring
      for the non-traumatic SCI patient need be more circumspect of individuals with
      these parameters to potentially prevent the problems necessitating acute care
      transfer.

PMID- 29355469
TI  - The relationship between handedness and valence: A gesture study.
AB  - People with different hand preferences assign positive and negative emotions to
      different sides of their bodies and produce co-speech gestures with their
      dominant hand when the content is positive. In this study, we investigated this
      side preference by handedness in both gesture comprehension and production.
      Participants watched faceless gesture videos with negative and positive content
      on eye tracker and were asked to retell the stories after each video. Results
      indicated no difference in looking preferences regarding being right- or left
      handed. Yet, an effect of emotional valence was observed. Participants spent more
      time looking to the right (actor's left) when the information was positive and to
      the left (actor's right) when the information was negative. Participants'
      retelling of stories revealed a handedness effect only for different types of
      gestures (representational vs beat). Individuals used their dominant hands for
      beat gestures. For representational gestures, while the right-handers used their
      right hands more, the left-handers gestured using both hands equally. Overall,
      the lack of significant difference between handedness and emotional content in
      both comprehension and production levels suggests that body-specific mental
      representations may not extend to the conversational level.

PMID- 29355471
TI  - Data and Safety Monitoring Committees in Clinical Trials.

PMID- 29355470
TI  - Novel Anticaries and Remineralization Agents: Future Research Needs.

PMID- 29355472
TI  - Special Issue: Multiplicity Issues in Clinical Trials.

PMID- 29355473
TI  - Evaluation of cockerel spermatozoa viability and motility by a novel enzyme based
      cell viability assay.
AB  - 1. The results of spermatozoa assessment by the WST-8 (2-[2-methoxy-4
      nitrophenyl]-3-[4-nitrophenyl]-5-[2,4-disulfophenyl]-2H-tetrazolium, monosodium
      salt) assay, flow cytometry (FC) or computer-assisted sperm analysis (CASA) were
      compared. 2. Different live/killed ratios of cockerel semen were serially diluted
      to 120, 60, and 30 * 106 cells/ml, and each sample was analysed by (1) WST-8
      assay at 0, 10, 20, 30, 40, 50, 60 min, (2) viability with FC, and (3) motility
      with CASA. 3. The WST-8 reduction rate was closely correlated with spermatozoa
      viability and motility. The optimal semen concentration for the WST-8 assay was
      120 * 106 cells/ml, and the standard curves for spermatozoa viability and
      motility predictions, respectively, were yviability60 = 162.8x + 104.96 (R2 =
      0.9594) after 60 min of incubation and ymotility40 = 225.09x + 96.299 (R2 =
      0.8475) after 40 min of incubation. 4. It was concluded that the WST-8 assay is
      useful for the practical evaluation of cockerel spermatozoa viability and
      motility. Compared to FC and CASA, the WST-8 assay does not require expensive and
      complex instrumentation in the lab. Furthermore, one well of the WST-8 reaction
      can be used to predict spermatozoa viability and motility at the same time, which
      all lead it to be efficient and economical for semen quality assessment.

PMID- 29355474
TI  - The "chicken-and-egg" development of political opinions.
AB  - Twin studies have revealed political ideology to be partially heritable.
      Neurological research has shown that ideological differences are reflected in
      brain structure and response, suggesting a direct genotype-phenotype link. Social
      and informational environments, however, also demonstrably affect brain structure
      and response. This leads to a "chicken-and-egg" question: do genes produce brains
      with ideological predispositions, causing the preferential absorption of
      consonant information and thereby forming an ideology, or do social and
      informational environments do most of the heavy lifting, with genetic evidence
      the spurious artifact of outdated methodology? Or are both inextricably
      intertwined contributors? This article investigates the relative contributions of
      genetic and environmental factors to ideological development using a role-play
      experiment investigating the development of opinions on a novel political issue.
      The results support the view that the process is bidirectional, suggesting that,
      like most traits, political ideology is produced by the complex interplay of
      genetic and (social/informational) environmental influences.

PMID- 29355475
TI  - Communities ready for takeoff.
AB  - Although much of the social science literature supports the importance of
      community assets for success in many policy areas, these assets are often
      overlooked when selecting communities for new infrastructure facilities.
      Extensive collaboration is crucial for the success of environmental and economic
      projects, yet it often is not adequately addressed when making siting decisions
      for new projects. This article develops a social asset framework that includes
      social, creative, and human capital to inform site-selection decisions. This
      framework is applied to the Northwest Advanced Renewables Alliance project to
      assess community suitability for biofuel-related developments. This framework is
      the first to take all necessary community assets into account, providing insight
      into successful site selection beyond current models. The framework not only
      serves as a model for future biorefinery projects but also guides tasks that
      depend on informed location selection for success.

PMID- 29355476
TI  - International Psychogeriatrics turns a new page: new editor begins his term.
AB  - It is a great honor and a privilege to be appointed as the new Editor-in-Chief of
      the International Psychogeriatrics (IPG), the flagship journal of the premier
      international geriatric psychiatry organization - the International
      Psychogeriatric Association (IPA). I am a proud Life Member of the IPA, and have
      been involved in different activities of the IPA over the past three decades.

PMID- 29355477
TI  - The political implications of epigenetics.
AB  - BACKGROUND: Epigenetics, which is just beginning to attract public attention and
      policy discussion, challenges conventional understanding of gene-environment
      interaction and intergenerational inheritance and perhaps much more besides.
      QUESTION: Does epigenetics challenge modern political ideologies? METHODS: I
      analyzed the narratives of obesity and epigenetics recently published in the more
      liberal New York Times and the more conservative Wall Street Journal. For the
      years 2010 through 2014, 50 articles on obesity and 29 articles on epigenetics
      were identified, and elements in their causal narratives were quantitatively
      analyzed using a well described narrative policy framework. FINDINGS: The
      narratives on obesity aligned with the two newspapers' reputed ideologies.
      However, the narratives on epigenetics aligned with neither ideology but freely
      mixed liberal and conservative elements. DISCUSSION: This small study may serve
      as a starting point for broader studies of epigenetics as it comes to affect
      political ideologies and, in turn, public policies. The narrative mix reported
      here could yet prove vulnerable to ideological capture, or, more optimistically,
      could portend the emergence of a "third-way" narrative using epigenetics to
      question atomistic individualism and allowing for less divisiveness in public
      health domains such as obesity.

PMID- 29355478
TI  - On recent advances in human engineering.
AB  - Advances in embryology, genetics, and regenerative medicine regularly attract
      attention from scientists, scholars, journalists, and policymakers, yet
      implications of these advances may be broader than commonly supposed.
      Laboratories culturing human embryos, editing human genes, and creating human
      animal chimeras have been working along lines that are now becoming intertwined.
      Embryogenic methods are weaving traditional in vivo and in vitro distinctions
      into a new "in vivitro" (in life in glass) fabric. These and other methods known
      to be in use or thought to be in development promise soon to bring society to
      startling choices and discomfiting predicaments, all in a global effort to supply
      reliably rejuvenating stem cells, to grow immunologically nonprovocative
      replacement organs, and to prevent, treat, cure, or even someday eradicate
      diseases having genetic or epigenetic mechanisms. With humanity's human
      engineering era now begun, procedural prohibitions, funding restrictions,
      institutional controls, and transparency rules are proving ineffective, and
      business incentives are migrating into the most basic life-sciences inquiries,
      wherein lie huge biomedical potentials and bioethical risks. Rights, health, and
      heritage are coming into play with bioethical presumptions and formal protections
      urgently needing reassessment.

PMID- 29355480
TI  - Sorting of a multi-subunit ubiquitin ligase complex in the endolysosome system.
AB  - The yeast Dsc E3 ligase complex has long been recognized as a Golgi-specific
      protein ubquitination system. It shares a striking sequence similarity to the
      Hrd1 complex that plays critical roles in the ER-associated degradation pathway.
      Using biochemical purification and mass spectrometry, we identified two novel Dsc
      subunits, which we named as Gld1 and Vld1. Surprisingly, Gld1 and Vld1 do not
      coexist in the same complex. Instead, they compete with each other to form two
      functionally independent Dsc subcomplexes. The Vld1 subcomplex takes the AP3
      pathway to reach the vacuole membrane, whereas the Gld1 subcomplex travels
      through the VPS pathway and is cycled between Golgi and endosomes by the
      retromer. Thus, instead of being Golgi-specific, the Dsc complex can regulate
      protein levels at three distinct organelles, namely Golgi, endosome, and vacuole.
      Our study provides a novel model of achieving multi-tasking for transmembrane
      ubiquitin ligases with interchangeable trafficking adaptors.

PMID- 29355481
TI  - Improving Follow-up and Reducing Barriers for Eye Screenings in Communities: The
      SToP Glaucoma Study.
AB  - PURPOSE: To evaluate factors associated with attendance to follow-up ophthalmic
      care, and to assess the impact of strategies to improve follow-up. DESIGN: Cross
      sectional study. METHODS: This is an ongoing study to develop an eye screening
      paradigm, focusing on African Americans >=50 years of age at multiple urban
      community sites in Baltimore, Maryland. Several strategies were employed aiming
      to increase follow-up attendance rates. Multivariable logistic regression was
      used to evaluate the associations between demographic, medical, and ocular
      factors with follow-up rate. RESULTS: The total number of referred patients
      presenting for a free eye examination (attendance rate) during the first phase,
      during the second phase, and overall was 686 (55.0%), 199 (63.8%), and 885
      (57.0%), respectively. In fully adjusted models, the odds ratio (95% confidence
      intervals) for attending the follow-up visit was 1.82 (1.19, 2.79) for screening
      in second phase vs first phase, 0.62 (0.39, 0.99) for screening sites that were 3
      to <5 miles vs <1 mile from the hospital, 1.70 (1.12, 2.59) in patients with body
      mass index >= 30 vs < 25 kg/m2, 2.03 (1.28, 3.21) in patients with presenting
      visual acuity < 20/40 vs >= 20/40, and 2.32 (1.24, 4.34) for patients with an
      abnormal vs normal macula. CONCLUSIONS: Obesity, short distance between screening
      sites and hospital, poor presenting visual acuity in the better eye, and an
      abnormal macula on fundus photography were associated with increased follow-up
      rate. Implementation of a combination of strategies effectively increased the
      follow-up rate. Wider adoption of these strategies in other screening programs
      has the potential to reduce the burden of visual impairment.

PMID- 29355479
TI  - Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene
      involved in age-related hearing loss.
AB  - Age-related hearing loss (ARHL) is the most common sensory deficit in the
      elderly. The disease has a multifactorial etiology with both environmental and
      genetic factors involved being largely unknown. SLC7A8/SLC3A2 heterodimer is a
      neutral amino acid exchanger. Here, we demonstrated that SLC7A8 is expressed in
      the mouse inner ear and that its ablation resulted in ARHL, due to the damage of
      different cochlear structures. These findings make SLC7A8 transporter a strong
      candidate for ARHL in humans. Thus, a screening of a cohort of ARHL patients and
      controls was carried out revealing several variants in SLC7A8, whose role was
      further investigated by in vitro functional studies. Significant decreases in
      SLC7A8 transport activity was detected for patient's variants (p.Val302Ile,
      p.Arg418His, p.Thr402Met and p.Val460Glu) further supporting a causative role for
      SLC7A8 in ARHL. Moreover, our preliminary data suggest that a relevant proportion
      of ARHL cases could be explained by SLC7A8 mutations.

PMID- 29355482
TI  - Inferior Decentration of Multifocal Intraocular Lenses in Myopic Eyes.
AB  - PURPOSE: To investigate the tilt and decentration of multifocal intraocular
      lenses (MfIOLs) implanted in myopic eyes. DESIGN: A prospective cohort study.
      METHODS: Twenty-eight myopic eyes and 56 emmetropic eyes were evaluated.
      Phacoemulsification with Tecnis ZMB00 MfIOL (Abbott Medical Optics, Santa Ana,
      California, USA) implantation was performed. At 1 year post-surgery, routine
      postoperative examinations were performed, and tilt and decentration of the
      MfIOLs, high-order aberrations, and modulation transfer function (MTF) were
      evaluated using the OPD-Scan III aberrometer (Nidek Co, Ltd, Gamagori, Japan).
      Subjective symptoms were assessed with a Quality of Vision questionnaire.
      RESULTS: Postoperative uncorrected distance visual acuity (VA), best-corrected
      distance VA, and uncorrected near VA did not differ between the 2 groups. The
      mean IOL tilt and horizontal decentration were not different between the control
      and myopic groups. However, the myopic group presented significantly inferior
      decentration in the capsular bag compared with the control group (-0.03 +/- 0.22
      mm vs -0.21 +/- 0.29 mm, P = .002). The overall decentration values were 0.32 +/-
      0.14 mm in the controls and 0.40 +/- 0.18 mm in the myopic group (P = .023).
      Axial length was negatively correlated with vertical decentration (r = -0.268, P
      = 0.014) and positively correlated with overall decentration (r = 0.334, P =
      .002). Worse aberration data, poorer MTF, and more subjective symptoms were also
      found in the myopic group than in the controls. CONCLUSION: Greater inferior
      decentration of MfIOLs and a consequent decrease in visual quality were found in
      myopic eyes, indicating that the increasing incompatibility between IOL and
      capsular bag size with axial length elongation should not be underestimated.

PMID- 29355483
TI  - Plasticity of the ligand binding pocket in the bitter taste receptor T2R7.
AB  - Bitter taste receptors (T2Rs) are a group of 25 G protein-coupled receptors
      (GPCRs) in humans. The cognate agonists and the mechanism of ligand binding to
      the majority of the T2Rs remain unknown. Here we report the first structure
      function analysis of T2R7 and study the ability of this receptor to bind to
      different agonists by site-directed mutagenesis. Screening of ligands for T2R7 in
      calcium based assays lead to the identification of novel compounds that activate
      this receptor. Quinine, diphenidol, dextromethorphan and diphenhydramine showed
      substantial activation of T2R7. Interestingly, these bitter compounds showed
      different pharmacological characteristics. To investigate the structural features
      in T2R7 that might contribute to the observed differences in agonist
      specificities, molecular model guided ligand docking and site-directed
      mutagenesis was pursued. Amino acids D65, D86, W89, N167, T169, W170, S181, T255
      and E271 in the ligand-binding pocket were replaced and the mutants characterized
      pharmacologically. Our results suggest D86, S181 and W170 present on the
      extracellular side of transmembrane 3 (TM3), TM5 and in extracellular loop 2
      (ECL2) are essential for agonist binding in T2R7. Mutations of these amino acids
      lead to loss-of-function. We also identified gain-of-function residues that are
      agonist specific. These results suggest that agonists bind at an extracellular
      site rather than deep within the TM core involving residues present in both ECL2
      and TM helices in T2R7. Similar to majority of the Class A GPCRs, ECL2 in T2R7
      plays a significant role in agonist binding and activation.

PMID- 29355484
TI  - Rapid detection of foodborne pathogen Listeria monocytogenes by strand exchange
      amplification.
AB  - A strand exchange amplification (SEA) method to detect foodborne pathogen
      Listeria monocytogenes was developed. SEA is a novel nucleic acid amplification
      method that only requires one pair of primers. The specie-specific primers were
      designed by targeting the 16S rRNA gene and the amplification reaction was
      performed as short as 60 min at 61  degrees C. Notably, SEA method could not only
      detect genomic DNA but also detect RNA by one step without requiring extra
      reverse transcription. The result could be visualized by naked eyes so that water
      bath pot would be the only equipment needed. Moreover, culture fluids and
      bacteria colony could be successfully detected without any pretreatment and the
      method displayed good specificity and strong anti-jamming capacity. These
      features greatly simplified the operating procedure and made SEA method be
      potential for developing point-of-care testing (POCT) devices to detect viable L.
      monocytogenes.

PMID- 29355485
TI  - COX16 is required for assembly of cytochrome c oxidase in human cells and is
      involved in copper delivery to COX2.
AB  - Cytochrome c oxidase (COX), complex IV of the mitochondrial respiratory chain, is
      comprised of 14 structural subunits, several prosthetic groups and metal
      cofactors, among which copper. Its biosynthesis involves a number of ancillary
      proteins, encoded by the COX-assembly genes that are required for the
      stabilization and membrane insertion of the nascent polypeptides, the synthesis
      of the prosthetic groups, and the delivery of the metal cofactors, in particular
      of copper. Recently, a modular model for COX assembly has been proposed, based on
      the sequential incorporation of different assembly modules formed by specific
      subunits. We have cloned and characterized the human homologue of yeast COX16. We
      show that human COX16 encodes a small mitochondrial transmembrane protein that
      faces the intermembrane space and is highly expressed in skeletal and cardiac
      muscle. Its knockdown in C. elegans produces COX deficiency, and its ablation in
      HEK293 cells impairs COX assembly. Interestingly, COX16 knockout cells retain
      significant COX activity, suggesting that the function of COX16 is partially
      redundant. Analysis of steady-state levels of COX subunits and of assembly
      intermediates by Blue-Native gels shows a pattern similar to that reported in
      cells lacking COX18, suggesting that COX16 is required for the formation of the
      COX2 subassembly module. Moreover, COX16 co-immunoprecipitates with COX2.
      Finally, we found that copper supplementation increases COX activity and restores
      normal steady state levels of COX subunits in COX16 knockout cells, indicating
      that, even in the absence of a canonical copper binding motif, COX16 could be
      involved in copper delivery to COX2.

PMID- 29355487
TI  - Mesothelioma With a Large Prevascular Lymph Node: N1 Involvement or Something
      Different?
AB  - A 64-year-old man presented with a large amount of right-sided pleural fluid on
      imaging, together with calcified pleural plaques and an enlarged nodular
      structure in the prevascular mediastinum, presumably an enlarged lymph node.
      Pleural biopsies were obtained during video-assisted thoracoscopic surgery to
      exclude malignancy. Histopathology showed an epithelial malignant pleural
      mesothelioma. Induction chemotherapy with cisplatin and pemetrexed was
      administered followed by an extended pleurectomy and decortication with
      systematic nodal dissection. Histopathology confirmed the diagnosis of a ypT3N0M0
      (stage IB) mesothelioma, and an unexpected thymoma type B2 (stage II) was
      discovered in the prevascular nodule. Simultaneous occurrence of a mesothelioma
      and thymoma is extremely rare.

PMID- 29355486
TI  - Low potential manganese ions as efficient electron donors in native anoxygenic
      bacteria.
AB  - Systematic control over molecular driving forces is essential for understanding
      the natural electron transfer processes as well as for improving the efficiency
      of the artificial mimics of energy converting enzymes. Oxygen producing
      photosynthesis uniquely employs manganese ions as rapid electron donors.
      Introducing this attribute to anoxygenic photosynthesis may identify evolutionary
      intermediates and provide insights to the energetics of biological water
      oxidation. This work presents effective environmental methods that substantially
      and simultaneously tune the redox potentials of manganese ions and the cofactors
      of a photosynthetic enzyme from native anoxygenic bacteria without the necessity
      of genetic modification or synthesis. A spontaneous coordination with bis-tris
      propane lowered the redox potential of the manganese (II) to manganese (III)
      transition to an unusually low value (~400 mV) at pH 9.4 and allowed its binding
      to the bacterial reaction center. Binding to a novel buried binding site elevated
      the redox potential of the primary electron donor, a dimer of
      bacteriochlorophylls, by up to 92 mV also at pH 9.4 and facilitated the electron
      transfer that is able to compete with the wasteful charge recombination. These
      events impaired the function of the natural electron donor and made BTP
      coordinated manganese a viable model for an evolutionary alternative.

PMID- 29355488
TI  - Smith-Lemli-Opitz Syndrome in a newborn infant with developmental abnormalities
      and low endogenous cholesterol.
AB  - BACKGROUND: Patients with Smith-Lemli-Opitz Syndrome (SLOS) have defective
      endogenous cholesterol synthesis, and present with decreased cholesterol levels
      and multiple developmental dysmorphologies. CASE DESCRIPTION: A newborn infant
      with normal XY karyotype and normal microarray was born with multiple
      developmental defects and ambiguous genitalia. The patient was diagnosed with
      SLOS, following biochemical genetic analysis of serum 7-DHC concentrations. The
      clinical course of the patient was further complicated by the comorbidities
      associated with SLOS and the bacterial infections. CONCLUSION: We provide a
      detailed biochemical profile of the SLOS patient. The report can help us further
      understand the pathological impacts of cholesterol synthesis deficiency and
      provide relevant clinical management with outcome of this rare genetic disorder.

PMID- 29355489
TI  - iTRAQ analysis of urinary proteins: Potential use of gelsolin and osteopontin to
      distinguish benign thyroid goiter from papillary thyroid carcinoma.
AB  - BACKGROUND: Benign thyroid goiter (BTG) and papillary thyroid carcinoma (PTC) are
      often interchangeably misdiagnosed. METHODS: Pooled urine samples of patients
      with BTG (n=10), patients with PTC (n=9) and healthy controls (n=10) were
      subjected to iTRAQ analysis and immunoblotting. RESULTS: The ITRAQ analysis of
      the urine samples detected 646 proteins, 18 of which showed significant altered
      levels (p<0.01; fold-change>1.5) between patients and controls. Whilst four
      urinary proteins were commonly altered in both BTG and PTC patients, 14 were
      unique to either BTG or PTC. Amongst these, four proteins were further chosen for
      validation using immunoblotting, and the enhanced levels of osteopontin in BTG
      patients and increased levels of a truncated gelsolin fragment in PTC patients,
      relative to controls, appeared to corroborate the findings of the iTRAQ analysis.
      CONCLUSION: The data of the present study is suggestive of the potential
      application of urinary osteopontin and gelsolin to discriminate patients with BTG
      from those with PTC non-invasively. However, this needs to be further validated
      in studies of individual urine samples.

PMID- 29355490
TI  - Expression of ICAM-1, E-cadherin, periostin and midkine in metastases of
      pancreatic ductal adenocarcinomas.
AB  - Development and progression of malignant tumors is in part characterized by the
      ability of a tumor cell to overcome cell-cell and cell-matrix adhesion and to
      disseminate in organs distinct from that in which they originated. This study was
      undertaken to analyze the clinical significance of the expression of the
      following cell-cell and cell-matrix adhesion molecules in pancreatic ductal
      adenocarcinomas (PDACs) and synchronous liver metastases: intercellular adhesion
      molecule 1 (ICAM-1), E-cadherin, periostin, and midkine (MK). ICAM-1, E-cadherin,
      periostin and MK expression was analyzed by immunohistochemistry on a tissue
      microarray containing 34 PDACs and 12 liver metastasis specimens. ICAM-1
      expression was predominantly localized in the membranes of the cells and was
      found in weak to moderate intensities in PDACs and liver metastases. E-cadherin
      expression was absent in the majority of PDACs and corresponding liver
      metastases. The secreted proteins periostin and MK were expressed in various
      intensities in primary cancers and liver metastases. Statistical analysis
      demonstrated that the expression levels of the analyzed markers were neither
      significantly associated with metastasis in PDACs nor with clinical outcome of
      patients. Our study shows that the expression of the cell-cell and cell-matrix
      adhesion molecules ICAM-1, E-cadherin, periostin and MK was not significantly
      linked to metastatic disease in PDACs. Moreover, our study excludes the analyzed
      markers as prognostic markers in PDACs.

PMID- 29355491
TI  - Restoration of mutant hERG stability by inhibition of HDAC6.
AB  - The human ether-a-go-go-related gene (hERG) encodes the alpha subunit of a
      rapidly activating delayed-rectifier potassium (IKr) channel. Mutations of the
      hERG cause long QT syndrome type 2 (LQT2). Acetylation of lysine residues occurs
      in a subset of non-histone proteins and this modification is controlled by both
      histone acetyltransferases and deacetylases (HDACs). The aim of this study was to
      clarify effects of HDAC(s) on wild-type (WT) and mutant hERG proteins. WThERG and
      two trafficking-defective mutants (G601S and R752W) were transiently expressed in
      HEK293 cells, which were treated with a pan-HDAC inhibitor Trichostatin A (TSA)
      or an isoform-selective HDAC6 inhibitor Tubastatin A (TBA). Both TSA and TBA
      increased protein levels of WThERG and induced expression of mature forms of the
      two mutants. Immunoprecipitation showed an interaction between HDAC6 and immature
      forms of hERG. Coexpression of HDAC6 decreased acetylation and, reciprocally,
      increased ubiquitination of hERG, resulting in its decreased expression. siRNA
      against HDAC6, as well as TBA, exerted opposite effects. Immunochemistry revealed
      that HDAC6 knockdown increased expression of the WThERG and two mutants both in
      the endoplasmic reticulum and on the cell surface. Electrophysiology showed that
      HDAC6 knockdown or TBA treatment increased the hERG channel current corresponding
      to the rapidly activating delayed-rectifier potassium current (IKr) in HEK293
      cells stably expressing the WT or mutants. Three lysine residues (K116, K495 and
      K757) of hERG were predicted to be acetylated. Substitution of these lysine
      residues with arginine eliminated HDAC6 effects. In HL-1 mouse cardiomyocytes,
      TBA enhanced endogenous ERG expression, increased IKr, and shortened action
      potential duration. These results indicate that hERG is a substrate of HDAC6.
      HDAC6 inhibition induced acetylation of hERG which counteracted ubiquitination
      leading its stabilization. HDAC6 inhibition may be a novel therapeutic option for
      LQT2.

PMID- 29355492
TI  - Racial and ethnic differences in patterns of long-acting reversible contraceptive
      use in the United States, 2011-2015.
AB  - OBJECTIVE: To investigate whether demographic, socioeconomic, and reproductive
      health characteristics affect long-acting reversible contraceptive (LARC) use
      differently by race-ethnicity. Results may inform the dialogue on racial pressure
      and bias in LARC promotion. STUDY DESIGN: Data derived from the 2011-2013 and
      2013-2015 National Surveys of Family Growth (NSFG). Our study sample included
      9321 women aged 15-44. Logistic regression analyses predicted current LARC use
      (yes vs. no). We tested interaction terms between race-ethnicity (non-Hispanic
      White, non-Hispanic Black, Hispanic) and covariates (for example, education,
      parity, poverty level) to explore whether their effects on LARC use vary by race
      ethnicity. RESULTS: In the race-interactions model, data did not show that low
      income and education predict LARC use more strongly among Black and Hispanic
      women than among White women. There was just one statistically significant race
      interaction: experience of unintended pregnancy (p=.014). Among Whites and
      Hispanics, women who reported ever experiencing an unintended pregnancy had a
      higher predicted probability of LARC use than those who did not. On the other
      hand, among Black women, the experience of unintended pregnancy was not
      associated with a higher predicted probability of LARC use. CONCLUSIONS: With the
      exception of the experience of unintended pregnancy, findings from this large,
      nationally representative sample of women suggest similar patterns in LARC use by
      race-ethnicity. IMPLICATIONS: Results from this analysis of NSFG data do not
      provide evidence that observed differences in LARC use by race-ethnicity
      represent socioeconomic disparities, and may assuage some concerns about
      reproductive coercion among women of color. Nevertheless, it is absolutely
      critical that providers use patient-centered approaches for contraceptive
      counseling that promote women's autonomy in their reproductive health care
      decision-making.

PMID- 29355493
TI  - Elongation factor-2 kinase acts downstream of p38 MAPK to regulate proliferation,
      apoptosis and autophagy in human lung fibroblasts.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic, fatal and progressive fibro
      proliferative lung disease, and fibroblast-to-myofibroblast differentiation is a
      crucial process in the development of IPF. Elongation factor-2 kinase (eEF2K) has
      been reported to play an important role in various disease types, but the role of
      eEF2K in IPF is unknown. In this study, we investigated the role of eEF2K in
      normal lung fibroblast (NHLF) proliferation, differentiation, apoptosis, and
      autophagy as well as the interaction between eEF2K and p38 MAPK signaling through
      in vitro experiments. We found that the inhibition of eEF2K markedly augmented
      cell proliferation and differentiation, suppressed apoptosis and autophagy, and
      reversed the anti-fibrotic effects of a p38 MAPK inhibitor. Together, our results
      indicate that eEF2K might inhibit TGF-beta1-induced NHLF proliferation and
      differentiation and activate NHLF cell apoptosis and autophagy through p38 MAPK
      signaling, which might ameliorate lung fibroblast-to-myofibroblast
      differentiation.

PMID- 29355494
TI  - ADAMTS-1 disrupts HGF/c-MET signaling and HGF-stimulated cellular processes in
      fibrosarcoma.
AB  - Extracellular matrix (ECM) serves as a reservoir for biologically active factors,
      such as growth factors and proteases that influence the tumor cell behavior.
      ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a
      secreted protease that has the ability to modify the ECM during physiological and
      pathological processes. Here, we analyzed the role played by ADAMTS-1 regulating
      HGF and TGF-beta1 activities in the high-grade fibrosarcoma cell line (HT1080).
      We generated HT1080 and HEK293T cells overexpressing ADAMTS-1. HT1080 cells
      overexpressing ADAMTS-1 (HT1080-MPA) exhibited a significant decrease in cell
      proliferation and migration velocity, both in presence of HGF. We obtained
      similar results with ADAMTS-1-enriched conditioned medium from other cell type.
      However, ADAMTS-1 overexpression failed to affect TGF-beta1 activity associated
      with HT1080 cell proliferation and migration velocity. Immunoblotting showed that
      ADAMTS-1 overexpression disturbs c-Met activation upon HGF stimulation.
      Downstream ERK1/2 and FAK signaling pathways are also influenced by this
      protease. Additionally, ADAMTS-1 decreased the size of the fibrosarcospheres,
      both under normal conditions and in the presence of HGF. Likewise, in presence of
      HGF, ADAMTS-1 overexpression in HT1080 disrupted microtumors formation in vivo.
      These microtumors, including individual cells, presented characteristics of non
      invasive lesions (rounded morphology). Our results suggest that ADAMTS-1 is
      involved in regulating HGF-related functions on fibrosarcoma cells. This protease
      may then represent an endogenous mechanism in controlling the bioavailability of
      different growth factors that have a direct influence on tumor cell behavior.

PMID- 29355495
TI  - Endocrine active metals, prenatal stress and enhanced neurobehavioral disruption.
AB  - Metals, including lead (Pb), methylmercury (MeHg) and arsenic (As), are long
      known developmental neurotoxicants. More recently, environmental context has been
      recognized to modulate metals toxicity, including nutritional state and stress
      exposure. Modulation of metal toxicity by stress exposure can occur through
      shared targeting of endocrine systems, such as the hypothalamic-pituitary-adrenal
      axis (HPA). Our previous rodent research has identified that prenatal stress (PS)
      modulates neurotoxicity of two endocrine active metals (EAMs), Pb and MeHg, by
      altering HPA and CNS systems disrupting behavior. Here, we review this research
      and further test the hypothesis that prenatal stress modulates metals
      neurotoxicity by expanding to test the effect of developmental As +/- PS
      exposure. Serum corticosterone and behavior was assessed in offspring of dams
      exposed to As +/- PS. PS increased female offspring serum corticosterone at
      birth, while developmental As exposure decreased adult serum corticosterone in
      both sexes. As + PS induced reductions in locomotor activity in females and
      reduced response rates on a Fixed Interval schedule of reinforcement in males,
      with the latter suggesting unique learning deficits only in the combined
      exposure. As-exposed males showed increased time in the open arms of an elevated
      plus maze and decreased novel object recognition whereas females did not. These
      data further confirm the hypothesis that combined exposure to chemical (EAMs) and
      non-chemical (PS) stressors results in enhanced neurobehavioral toxicity. Given
      that humans are exposed to multiple environmental risk factors that alter
      endocrine function in development, such models are critical for risk assessment
      and public health protection, particularly for children.

PMID- 29355496
TI  - The glycosomal alkyl-dihydroxyacetonephosphate synthase TbADS is essential for
      the synthesis of ether glycerophospholipids in procyclic trypanosomes.
AB  - Glycerophospholipids are the main constituents of the biological membranes in
      Trypanosoma brucei, which causes sleeping sickness in humans. The present work
      reports the characterization of the alkyl-dihydroxyacetonephosphate synthase
      TbADS that catalyzes the committed step in ether glycerophospholipid
      biosynthesis. TbADS localizes to the glycosomal lumen. TbADS complemented a null
      mutant of Leishmania major lacking alkyl-dihydroxyacetonephosphate synthase
      activity and restored the formation of normal form of the ether lipid based
      virulence factor lipophosphoglycan. Despite lacking alkyl
      dihydroxyacetonephosphate synthase activity, a null mutant of TbADS in procyclic
      trypanosomes remained viable and exhibited normal growth. Comprehensive analysis
      of cellular glycerophospholipids showed that TbADS was involved in the
      biosynthesis of all ether glycerophospholipid species, primarily found in the PE
      and PC classes.

PMID- 29355497
TI  - Novel arylidene derivatives of quinoline based thiazolidinones: Synthesis, in
      vitro, in vivo and in silico study as antimalarials.

PMID- 29355499
TI  - Protein deficiency lowers resistance of Mormon crickets to the pathogenic fungus
      Beauveria bassiana.
AB  - Little is known about the effects of dietary macronutrients on the capacity of
      insects to ward off a fungal pathogen. Here we tested the hypothesis that Mormon
      crickets fed restricted protein diets have lower enzymatic assays of generalized
      immunity, slower rates of encapsulation of foreign bodies, and greater mortality
      from infection by Beauveria bassiana, a fungal pathogen. Beginning in the last
      nymphal instar, Mormon crickets were fed a high, intermediate, or low protein
      diet with correspondingly low, intermediate, or high carbohydrate proportions.
      After they eclosed to adult, we drew hemolymph, topically applied B. bassiana,
      maintained them on diet treatments, and measured mortality for 21 days. Mormon
      crickets fed high protein diets had higher prophenoloxidase titers, greater
      encapsulation response, and higher survivorship to Beauveria fungal infection
      than those on low protein diets. We replicated the study adding very high and
      very low protein diets to the treatments. A high protein diet increased
      phenoloxidase titers, and those fed the very high protein diet had more
      circulating prophenoloxidase. Mormon crickets fed the very low protein diet were
      the most susceptible to B. bassiana infection, but the more concentrated
      phenoloxidase and prophenoloxidase associated with the highest protein diets did
      not confer the greatest protection from the fungal pathogen as in the first
      replicate. We conclude that protein-restricted diets caused Mormon crickets to
      have lower phenoloxidase titers, slower encapsulation of foreign bodies, and
      greater mortality from B. bassiana infection than those fed high protein diets.
      These results support the nutrition-based dichotomy of migrating Mormon crickets,
      protein-deficient ones are more susceptible to pathogenic fungi whereas
      carbohydrate-deficient ones are more vulnerable to bacterial challenge.

PMID- 29355500
TI  - Influenza Hemifusion Phenotype Depends on Membrane Context: Differences in Cell
      Cell and Virus-Cell Fusion.
AB  - Influenza viral entry into the host cell cytoplasm is accomplished by a process
      of membrane fusion mediated by the viral hemagglutinin protein. Hemagglutinin
      acts in a pH-triggered fashion, inserting a short fusion peptide into the host
      membrane followed by refolding of a coiled-coil structure to draw the viral
      envelope and host membranes together. Mutations to this fusion peptide provide an
      important window into viral fusion mechanisms and protein-membrane interactions.
      Here, we show that a well-described fusion peptide mutant, G1S, has a phenotype
      that depends strongly on the viral membrane context. The G1S mutant is well known
      to cause a "hemifusion" phenotype based on experiments in transfected cells,
      where cells expressing G1S hemagglutinin can undergo lipid mixing in a pH
      triggered fashion similar to virus but will not support fusion pores. We compare
      fusion by the G1S hemagglutinin mutant expressed either in cells or in influenza
      virions and show that this hemifusion phenotype occurs in transfected cells but
      that native virions are able to support full fusion, albeit at a slower rate and
      10-100* reduced infectious titer. We explain this with a quantitative model where
      the G1S mutant, instead of causing an absolute block of fusion, alters the
      protein stoichiometry required for fusion. This change slightly slows fusion at
      high hemagglutinin density, as on the viral surface, but at lower hemagglutinin
      density produces a hemifusion phenotype. The quantitative model thus reproduces
      the observed virus-cell and cell-cell fusion phenotypes, yielding a unified
      explanation where membrane context can control the observed viral fusion
      phenotype.

PMID- 29355501
TI  - On the Trails of the Proteasome Fold: Structural and Functional Analysis of the
      Ancestral beta-Subunit Protein Anbu.
AB  - The 20S proteasome is a key player in eukaryotic and archaeal protein
      degradation, but its progenitor in eubacteria is unknown. Recently, the ancestral
      beta-subunit protein (Anbu) was predicted to be the evolutionary precursor of the
      proteasome. We crystallized Anbu from Hyphomicrobium sp. strain MC1 in four
      different space groups and solved the structures by SAD-phasing and Patterson
      search calculation techniques. Our data reveal that Anbu adopts the classical
      fold of Ntn-hydrolases, but its oligomeric state differs from that of barrel
      shaped proteases. In contrast to their typical architecture, the Anbu protomer is
      a tightly interacting dimer that can assemble into a helical superstructure.
      Although Anbu features a catalytic triad of Thr1Ogamma, Asp17Odelta1 and
      Lys32Nepsilon, it is unable to hydrolyze standard protease substrates. The lack
      of activity might be caused by the incapacity of Thr1NH2 to function as a
      Bronsted acid during substrate cleavage due to its missing activation via
      hydrogen bonding. Altogether, we demonstrate that the topology of the proteasomal
      fold is conserved in Anbu, but whether it acts as a protease still needs to be
      clarified.

PMID- 29355498
TI  - Zn2+-induced disruption of neuronal mitochondrial function: Synergism with Ca2+,
      critical dependence upon cytosolic Zn2+ buffering, and contributions to neuronal
      injury.
AB  - Excitotoxic Zn2+ and Ca2+ accumulation contributes to neuronal injury after
      ischemia or prolonged seizures. Synaptically released Zn2+ can enter postsynaptic
      neurons via routes including voltage sensitive Ca2+ channels (VSCC), and, more
      rapidly, through Ca2+ permeable AMPA channels. There are also intracellular Zn2+
      binding proteins which can either buffer neuronal Zn2+ influx or release bound
      Zn2+ into the cytosol during pathologic conditions. Studies in culture highlight
      mitochondria as possible targets of Zn2+; cytosolic Zn2+ can enter mitochondria
      and induce effects including loss of mitochondrial membrane potential
      (DeltaPsim), mitochondrial swelling, and reactive oxygen species (ROS)
      generation. While brief (5 min) neuronal depolarization (to activate VSCC) in the
      presence of 300 MUM Zn2+ causes substantial delayed neurodegeneration, it only
      mildly impacts acute mitochondrial function, raising questions as to
      contributions of Zn2+-induced mitochondrial dysfunction to neuronal injury. Using
      brief high (90 mM) K+/Zn2+ exposures to mimic neuronal depolarization and
      extracellular Zn2+ accumulation as may accompany ischemia in vivo, we examined
      effects of disrupted cytosolic Zn2+ buffering and/or the presence of Ca2+, and
      made several observations: 1. Mild disruption of cytosolic Zn2+ buffering-while
      having little effects alone-markedly enhanced mitochondrial Zn2+ accumulation and
      dysfunction (including loss of ?Psim, ROS generation, swelling and respiratory
      inhibition) caused by relatively low (10-50 MUM) Zn2+ with high K+. 2. The
      presence of Ca2+ during the Zn2+ exposure decreased cytosolic and mitochondrial
      Zn2+ accumulation, but markedly exacerbated the consequent dysfunction. 3.
      Paralleling effects on mitochondria, disruption of buffering and presence of Ca2+
      enhanced Zn2+-induced neurodegeneration. 4. Zn2+ chelation after the high K+/Zn2+
      exposure attenuated both ROS production and neurodegeneration, supporting the
      potential utility of delayed interventions. Taken together, these data lend
      credence to the idea that in pathologic states that impair cytosolic Zn2+
      buffering, slow uptake of Zn2+ along with Ca2+ into neurons via VSCC can disrupt
      the mitochondria and induce neurodegeneration.

PMID- 29355502
TI  - The influence of temperature and salinity on mortality of recently recruited blue
      crabs, Callinectes sapidus, naturally infected with Hematodinium perezi
      (Dinoflagellata).
AB  - The parasitic dinoflagellate Hematodinium perezi is highly prevalent in juvenile
      blue crabs, Callinectes sapidus, along the eastern seaboard of the USA. Although
      the parasite is known to kill adult crabs, the mortality rate of naturally
      infected juvenile crabs remains unknown. We analyzed the influence of temperature
      and salinity on the mortality of recently recruited blue crabs that were
      naturally infected with H. perezi. Over 492 juvenile crabs (infected, n = 282;
      uninfected controls, n = 210) were held individually in six-well plates and held
      at six temperatures (4, 10, 15, 20, 25, and 30  degrees C) or three salinities
      (5, 15, and 30 psu) for a maximum of 90 days. Mortality of infected crabs was 10
      times higher at elevated temperatures (25 and 30  degrees C) and salinity (30
      psu) compared to uninfected control treatments. By contrast, infected crabs
      exposed to mild temperatures (10, 15, and 20  degrees C) showed a high survival
      (>80%), no different than uninfected control treatments. Infected crabs at the
      lowest temperature (4  degrees C) exhibited a high mortality, but the intensity
      of infection was lower than in the other temperature treatments. In addition,
      this study revealed the optimal temperature (25  degrees C) and salinity (30 psu)
      for H. perezi to progress in its life cycle leading to sporulation in juvenile
      crabs; 31.6% (19/60) of crabs held under these conditions released dinospores of
      H. perezi after 10 days. Crabs held at other temperatures did not release
      dinospores over the time course of the experiment. Infected crabs were capable of
      molting and in most cases molted at the same frequency as uninfected crabs
      serving as controls. The mortality observed in this study indicates that early
      benthic juveniles will experience significant mortality due to H. perezi with
      increasing ocean temperatures and that this mortality may be a significant factor
      in the recruitment of blue crabs to high salinity regions.

PMID- 29355503
TI  - REV-ERBbeta is required to maintain normal wakefulness and the wake-inducing
      effect of dual REV-ERB agonist SR9009.
AB  - Circadian signaling regulates and synchronizes physiological and behavioral
      processes, such as feeding, metabolism, and sleep cycles. The endogenous
      molecular machinery that regulates circadian activities is located in the
      suprachiasmatic nucleus of the hypothalamus. The REV-ERBs are transcription
      factors that play key roles in the regulation of the circadian clock and
      metabolism. Using pharmacological methods, we recently demonstrated the
      involvement of the REV-ERBs in sleep architecture. Another group reported a
      delayed response to sleep deprivation and altered sleep cycles in REV-ERBalpha
      null mice, indicating a role of REV-ERBalpha in sleep. Given that REV-ERBbeta is
      structurally and functionally similar to REV-ERBalpha, we investigated the role
      of REV-ERBbeta in sleep and wakefulness by assessing electroencephalographic
      recordings in REV-ERBbeta deficient mice and the mechanism underlying effects of
      loss of REV-ERBbeta on sleep. Our data suggest that REV-ERBbeta is involved in
      the maintenance of wakefulness during the activity period. In addition, REV
      ERBbeta-deficient mice administered with dual REV-ERB agonist SR9009, failed to
      show drug-induced wake increase. Finally, the expression of a number of genes
      known to mediate sleep and wakefulness were altered in REV-ERBbeta null mice.

PMID- 29355504
TI  - PARP-1 inhibition ameliorates elastase induced lung inflammation and emphysema in
      mice.
AB  - COPD is associated with high morbidity and mortality and no effective treatment
      is available till date. We have previously reported that PARP-1 plays an
      important role in the establishment of airway inflammation associated with asthma
      and ALI. In the present work, we have evaluated the beneficial effects of PARP-1
      inhibition on COPD pathogenesis utilizing elastase induced mouse model of the
      disease. Our data show that PARP-1 inhibition by olaparib significantly reduced
      the elastase-induced recruitment of inflammatory cells particularly neutrophils
      in the lungs of mice when administered at a dose of 5 mg/kg b.wt (i.p.).
      Reduction in the lung inflammation was associated with suppressed myeloperoxidase
      activity. Further, the drug restored the redox status in the lung tissues towards
      normal as reflected by the levels of ROS, GSH and MDA. Olaparib administration
      prior to elastase instillation blunted the phosphorylation of P65-NF-kappaB at
      Ser 536 without altering phosphorylation of its inhibitor IkappaBalpha in the
      lungs. Furthermore, olaparib down regulated the elastase-induced expression of NF
      kappaB dependent pro-inflammatory cytokines (TNF-A, IL-6), chemokine (MIP-2) and
      growth factor (GCSF) severely both at the mRNA and protein levels. Additionally,
      PARP-1 heterozygosity suppressed the recruitment of inflammatory cells and
      production of TNF-A, IL-6, MIP-2 and GCSF in the BALF to the similar extent as
      exhibited by olaparib administration. Finally, PARP-1 inhibition by olaparib or
      gene deletion protected against elastase-induced emphysema markedly. Overall, our
      data strongly suggest that PARP-1 plays a critical role in elastase induced lung
      inflammation and emphysema, and thus may be a new drug target candidate in COPD.

PMID- 29355505
TI  - Glutazumab, a novel long-lasting GLP-1/anti-GLP-1R antibody fusion protein,
      exerts anti-diabetic effects through targeting dual receptor binding sites.
AB  - AIMS: Glucagon like-peptide-1 (GLP-1)-based drugs have been proposed as mono- or
      combined therapy for type 2 diabetes mellitus. Thus we characterized a novel
      antibody fusion protein engineered by linking the human GLP-1 derivative to a
      humanized GLP-1 receptor (GLP-1R) antibody via a peptide linker. MATERIALS AND
      METHODS: Glutazumab was characterized by receptor binding and reporter activation
      assays, and its specificity was investigated with the aid of the cognate receptor
      antagonist exendin (9-39) and antibody Ab1. Pharmacokinetics was evaluated in
      Sprague-Dawley (SD) rats and cynomolgus monkeys, and pharmacodynamics was
      assessed in normal ICR and spontaneous type 2 diabetic KKAy mice. Hypoglycemic
      effects were evaluated after acute administration and glucose metabolism and beta
      cell function were assessed with repeated administrations. Dulaglutide was a
      positive control in all experiments. RESULTS: Glutazumab significantly bound and
      activated GLP-1R, but the receptor antagonist exendin (9-39) did not inhibit the
      activation except when combined with Ab1. Single injection of glutazumab reduced
      the blood glucose in ICR mice and KKAy mice, and the half-lives in SD rats and
      cynomolgus monkeys were 18 h and 33.6 h. Repeated injections of glutazumab
      controlled glycemic fluctuations and improved beta-cell function in KKAy mice.
      CONCLUSIONS: As a novel GLP-1R agonist, glutazumab may be a potential treatment
      for T2DM.

PMID- 29355506
TI  - Diagnostic Accuracy of the Veteran Affairs' Traumatic Brain Injury Screen.
AB  - OBJECTIVE: To comprehensively estimate the diagnostic accuracy and reliability of
      the Department of Veterans Affairs (VA) Traumatic Brain Injury (TBI) Clinical
      Reminder Screen (TCRS). DESIGN: Cross-sectional, prospective, observational study
      using the Standards for Reporting of Diagnostic Accuracy criteria. SETTING: Three
      VA Polytrauma Network Sites. PARTICIPANTS: Operation Iraqi Freedom, Operation
      Enduring Freedom veterans (N=433). MAIN OUTCOME MEASURES: TCRS, Comprehensive TBI
      Evaluation, Structured TBI Diagnostic Interview, Symptom Attribution and
      Classification Algorithm, and Clinician-Administered Posttraumatic Stress
      Disorder (PTSD) Scale. RESULTS: Forty-five percent of veterans screened positive
      on the TCRS for TBI. For detecting occurrence of historical TBI, the TCRS had a
      sensitivity of .56 to .74, a specificity of .63 to .93, a positive predictive
      value (PPV) of 25% to 45%, a negative predictive value (NPV) of 91% to 94%, and a
      diagnostic odds ratio (DOR) of 4 to 13. For accuracy of attributing active
      symptoms to the TBI, the TCRS had a sensitivity of .64 to .87, a specificity of
      .59 to .89, a PPV of 26% to 32%, an NPV of 92% to 95%, and a DOR of 6 to 9. The
      sensitivity was higher for veterans with PTSD (.80-.86) relative to veterans
      without PTSD (.57-.82). The specificity, however, was higher among veterans
      without PTSD (.75-.81) relative to veterans with PTSD (.36-.49). All indices of
      diagnostic accuracy changed when participants with questionably valid (QV) test
      profiles were eliminated from analyses. CONCLUSIONS: The utility of the TCRS to
      screen for mild TBI (mTBI) depends on the stringency of the diagnostic reference
      standard to which it is being compared, the presence/absence of PTSD, and QV test
      profiles. Further development, validation, and use of reproducible diagnostic
      algorithms for symptom attribution after possible mTBI would improve diagnostic
      accuracy.

PMID- 29355507
TI  - What Are the Determinants of Dental Care Expenditures in Institutions for Adults
      With Disabilities? Findings From a National Survey.
AB  - OBJECTIVE: To analyze the determinants of dental care expenditures in
      institutions for adults with disabilities. DESIGN: Health and disability survey
      and insurance database. SETTING: Institutional setting. PARTICIPANTS: Adults
      (N=2222) living in institutions for people with cognitive, sensory, and mobility
      disabilities. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We used a
      Heckman selection model to correct for potential sample selection bias due to the
      high percentage of non-dental care users. The Heckman selection model is a 2-step
      statistical approach based on the simultaneous estimation of 2 multiple
      regression models-a selection equation (step 1) and an outcome equation (step 2)
      offering a means of correcting for nonrandomly selected samples. The selection
      equation modeled whether the individual had consulted a dentist at least once,
      whereas the outcome equation explained the dental care expenditures. Disability
      severity was assessed by scoring mobility and cognitive functional limitations.
      Regressions also included sociodemographic characteristics and other health
      related variables. RESULTS: Individuals with the highest cognitive limitation
      scores, without family visits, without supplementary health insurance, and with
      poor oral health status were less likely to consult a dentist. After controlling
      for potential selection bias, the only variable that remained statistically
      significant in the outcome equation was the oral health status: when individuals
      with poor health status had consulted at least once, they had a higher level of
      dental care expenditure. CONCLUSIONS: Functional limitations were barriers to
      accessing dental care even in institutions for adult with disabilities. These
      barriers should be overcome because they may worsen their oral health status and
      well-being. Given the lack of literature on this specific topic, our results are
      important from a policy perspective. Health authorities should be alerted by
      these findings.

PMID- 29355508
TI  - Intracranial Calcification Due to Hypoparathyroidism.

PMID- 29355509
TI  - Severe Asthma in Primary Care: Identification and Management.
AB  - Most patients with asthma are managed by primary care providers. Severe asthma is
      associated with substantial morbidity and health care resource use, and long-term
      sequelae of severe asthma include airway remodeling and a greater risk of
      developing chronic obstructive pulmonary disease. These consequences highlight
      the importance of early identification and improved management of patients with
      severe asthma. Although treatment guidelines can be confusing and it can be
      difficult to keep abreast of updates, routine assessments of lung function,
      frequency and severity of exacerbations, symptom control, and medication
      adherence in the primary care setting provide the necessary information for
      identifying severe asthma and determining appropriate management strategies. An
      increased understanding of asthma pathophysiology and its relationship to disease
      activity has identified therapeutic targets and associated biomarkers. Biologic
      therapies directed at these targets offer individualized targeted treatment of
      severe asthma. We review evidence-based guidelines for identification and
      management of severe asthma, clarify the relationship of asthma control and
      asthma severity, and provide an overview of new biologic therapies offering
      additional treatment options for patients with severe asthma.

PMID- 29355510
TI  - Oxygen Therapy in Patients with Acute Myocardial Infarction: A Systemic Review
      and Meta-Analysis.
AB  - OBJECTIVE: Oxygen therapy is frequently used for patients with acute myocardial
      infarction. The aim of this study is to perform a systematic review and meta
      analysis to compare the outcomes of oxygen therapy versus no oxygen therapy in
      post-acute myocardial infarction settings. METHODS: A systematic search of
      electronic databases was conducted for randomized studies, which reported
      cardiovascular events in oxygen versus no oxygen therapy. The evaluated outcomes
      were all-cause mortality, recurrent coronary events (ischemia or myocardial
      infarction), heart failure, and arrhythmias. Summary-adjusted risk ratios (RRs)
      were calculated by the random effects DerSimonian and Laird model. The risk of
      bias of the included studies was assessed by Cochrane scale. RESULTS: Our meta
      analysis included a total of 7 studies with 3842 patients who received oxygen
      therapy and 3860 patients without oxygen therapy. Oxygen therapy did not decrease
      the risk of all-cause mortality (pooled RR, 0.99; 95% confidence interval [CI],
      0.81-1.21; P = .43), recurrent ischemia or myocardial infarction (pooled RR,
      1.19; 95% CI, 0.95-1.48; P = .75), heart failure (pooled RR, 0.94; 95% CI, 0.61
      1.45; P = .348), and occurrence of arrhythmia events (pooled RR, 1.01; 95% CI,
      0.85-1.2; P = .233) compared with the no oxygen arm. CONCLUSIONS: This meta
      analysis confirms the lack of benefit of routine oxygen therapy in patients with
      acute myocardial infarction with normal oxygen saturation levels.

PMID- 29355511
TI  - Low-Dose d-Amphetamine Induced Regression of Liver Fat Deposits in Dercum
      Disease.
AB  - BACKGROUND: Dercum disease is a rare disorder of painful subcutaneous adipose
      tissue masses typically presenting as a constellation of signs and symptoms
      affecting most organs, including slow lymphatic flow and fatty liver. METHOD: The
      University of Arizona Institutional Review Board considered this report exempt
      after patient consent. Multislice, multisequence magnetic resonance imaging (MRI)
      of the abdomen and pelvis was performed prior to and after d-amphetamine, with
      and without intravenous gadolinium. RESULTS: Initial MRI demonstrated hepatic
      steatosis in Case 1; Case 2 had 2-subcentimeter lipid foci within the liver.
      Initiation of 10-20 mg d-amphetamine decreased liver lipid deposition from 16% to
      4% in Case 1 and resolved fat deposits in Case 2 after ~1 year. CONCLUSION: There
      is a dire need for novel treatment options for nonalcoholic fatty liver disease
      to prevent progression to cirrhosis. Reduction of liver fat by d-amphetamine
      suggests a potential therapeutic role in nonalcoholic fatty liver disease.

PMID- 29355512
TI  - Drivers of Application Inflation: A National Survey of Internal Medicine
      Residents.

PMID- 29355513
TI  - Sweet's Syndrome Mimicking Anti-Neutrophil Cytoplasmic Antibodies-Associated
      Vasculitis.

PMID- 29355515
TI  - Spliceosome-Associated Protein 130 Exacerbates Alcohol-Induced Liver Injury by
      Inducing NLRP3 Inflammasome-Mediated IL-1beta in Mice.
AB  - Excessive alcohol consumption leads to chronic liver diseases. Macrophage
      inducible C-type lectin (Mincle) is a C-type lectin receptor that recognizes
      spliceosome-associated protein 130 (SAP130) known as an endogenous ligand
      released from dying cells. The aim was to examine the role of Mincle-SAP130 in
      the pathogenesis of alcoholic liver disease. Alcohol-induced liver injury was
      induced in wild-type (WT) and Mincle knockout (KO) mice by using a chronic-binge
      ethanol-feeding model. Mincle KO mice showed significant lower hepatic steatosis,
      inflammation with neutrophil infiltration, and fibrosis compared with WT mice
      after alcohol feeding. In contrast, Mincle activation exacerbated alcohol-induced
      liver injury. Kupffer cells (KCs) are major sources of Mincle. IL-1beta
      expression was significantly down-regulated in Mincle KO mice compared with that
      in WT mice after alcohol consumption. Interestingly, expression and production of
      IL-1beta were significantly decreased in SAP130-treated KCs isolated from leucine
      rich-containing family pyrin domain containing-3-deficient mice compared with
      those in WT KCs. Such results were also observed in cells treated with SAP130
      plus Syk inhibitor. Furthermore, infiltration of invariant natural killer T cells
      was decreased in livers of Mincle KO mice. Finally, inhibition of Syk signaling
      ameliorated alcohol-induced liver injury. Collectively, these results
      demonstrated that interaction between Mincle and SAP130 may promote the
      progression of alcoholic liver disease by IL-1beta production in KCs and
      consequently increase inflammatory immune cell infiltration.

PMID- 29355514
TI  - A Shared Pattern of beta-Catenin Activation in Bronchopulmonary Dysplasia and
      Idiopathic Pulmonary Fibrosis.
AB  - Wnt/beta-catenin signaling is necessary for normal lung development, and abnormal
      Wnt signaling contributes to the pathogenesis of both bronchopulmonary dysplasia
      (BPD) and idiopathic pulmonary fibrosis (IPF), fibrotic lung diseases that occur
      during infancy and aging, respectively. Using a library of human normal and
      diseased human lung samples, we identified a distinct signature of nuclear
      accumulation of beta-catenin phosphorylated at tyrosine 489 and epithelial cell
      cytosolic localization of beta-catenin phosphorylated at tyrosine 654 in early
      normal lung development and fibrotic lung diseases BPD and IPF. Furthermore, this
      signature was recapitulated in murine models of BPD and IPF. Image analysis of
      immunofluorescence colocalization demonstrated a consistent pattern of elevated
      nuclear phosphorylated beta-catenin in the lung epithelium and surrounding
      mesenchyme in BPD and IPF, closely resembling the pattern observed in 18-week
      fetal lung. Nuclear beta-catenin phosphorylated at tyrosine 489 associated with
      an increased expression of Wnt target gene AXIN2, suggesting that the observed
      beta-catenin signature is of functional significance during normal development
      and injury repair. The association of specific modifications of beta-catenin
      during normal lung development and again in response to lung injury supports the
      widely held concept that repair of lung injury involves the recapitulation of
      developmental programs. Furthermore, these observations suggest that beta-catenin
      phosphorylation has potential as a therapeutic target for the treatment and
      prevention of both BPD and IPF.

PMID- 29355517
TI  - Eicosapentaenoic acid and docosahexaenoic acid have distinct membrane locations
      and lipid interactions as determined by X-ray diffraction.
AB  - Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differentially
      influence lipid oxidation, signal transduction, fluidity, and cholesterol domain
      formation, potentially due in part to distinct membrane interactions. We used
      small angle X-ray diffraction to evaluate the EPA and DHA effects on membrane
      structure. Membrane vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC) and cholesterol (C) (0.3C:POPC mole ratio) were prepared
      and treated with vehicle, EPA, or DHA (1:10 mol ratio to POPC). Electron density
      profiles generated from the diffraction data showed that EPA increased membrane
      hydrocarbon core electron density over a broad area, up to +/- 20 A from the
      membrane center, indicating an energetically favorable extended orientation for
      EPA likely stabilized by van der Waals interactions. By contrast, DHA increased
      electron density in the phospholipid head group region starting at +/- 12 A from
      the membrane center, presumably due to DHA-surface interactions, with coincident
      reduction in electron density in the membrane hydrocarbon core centered +/- 7-9 A
      from the membrane center. The membrane width (d-space) decreased by 5 A in the
      presence of vehicle as the temperature increased from 10  degrees C to 30 
      degrees C due to increased acyl chain trans-gauche isomerizations, which was
      unaffected by addition of EPA or DHA. The influence of DHA on membrane structure
      was modulated by temperature changes while the interactions of EPA were
      unaffected. The contrasting EPA and DHA effects on membrane structure indicate
      distinct molecular locations and orientations that may contribute to observed
      differences in biological activity.

PMID- 29355518
TI  - Rapid single-step formation of liposomes by flow assisted stationary phase
      interdiffusion.
AB  - Laboratory preparation of unilamellar liposomes often involves multiple steps
      carried out over several hours to achieve a monodisperse size distribution. Here,
      we present a methodology based on a recently introduced lipid self-assembly
      principle-stationary phase interdiffusion (SPI)-to prepare large unilamellar
      vesicles (LUVs) of a monodisperse population in a short period of about 10 min.
      The stationary interface between a lipid-ethanol phase and an aqueous phase is
      created by a density difference induced convective flow in a horizontal
      capillary. The average size of the liposomes, as expected from the SPI principle,
      is modulated only by the temperature and the type of lipids. Lipid concentration,
      ethanol content, pH of the aqueous phase, and the time duration of the experiment
      have little influence on the mean diameter of the vesicles. This simple
      methodology can be easily carried out with a capillary and a micro-needled
      syringe and provides a rapid production tool for researchers requiring
      reproducible liposome suspensions. Refined natural lipids, based on soy and egg
      lecithin mixtures, yield LUVs in the range 100-200 nm, suitable for drug delivery
      applications.

PMID- 29355519
TI  - Successful sperm cryopreservation of the brown-marbled grouper, Epinephelus
      fuscoguttatus using propylene glycol as cryoprotectant.
AB  - This study developed the cryopreservation of brown-marbled grouper spermatozoa
      for practical application. We examined 32 cryodiluents, developed from four types
      of cryoprotectants [propylene glycol (PG), dimethyl-sulphoxide (Me2SO), dimethyl
      acetamide (DMA) and ethylene glycol (EG)] at four concentrations of 5, 10, 15 and
      20% in combination with two extenders [Fetal bovine serum (FBS) and artificial
      seminal plasma (ASP). Cooling rates were examined by adjusting the height of
      straws (2.5-12.5 cm) from the liquid nitrogen (LN) vapor and cooled for 5 min
      before immersion into LN. DNA laddering was used to detect DNA damage in
      cryopreserved sperm. In fertilization trials, 0.5 g of eggs was mixed with
      cryopreserved sperm stored for 30 days in LN. The best motility of post-thaw
      sperm was achieved using 15% PG + 85% FBS (76.7 +/- 8.8%); 10% PG + 90% FBS was
      also effective as cryodiluent. Generally, FBS gave better post-thaw motility
      compared to ASP. The optimum cooling rate was at 17.6  degrees C min-1 obtained
      by freezing at the height of 7.5 cm surface of LN. The results obtained showed
      that cryopreserved sperm of brown-marbled grouper suffered slight DNA
      fragmentation, which resulted in significantly lower motility. However, the
      fertilization (90.9 +/- 0.5%), hatching (64.5 +/- 4.1%) and deformity rates (3.8
      +/- 0.2%) obtained from cryopreserved sperm showed no significant difference with
      fresh sperm. These findings show that the developed protocol for cryopreservation
      of brown-marbled grouper sperm was viable and will be useful for successful
      breeding and seed production of brown-marbled grouper.

PMID- 29355516
TI  - Syndecan-1 Controls Lung Tumorigenesis by Regulating miRNAs Packaged in Exosomes.
AB  - Syndecan-1 is a transmembrane proteoglycan expressed prominently by lung
      epithelium and has pleiotropic functions such as regulating cell migration,
      proliferation, and survival. Loss of syndecan-1 expression by lung cancer cells
      is associated with higher-grade cancers and worse clinical prognosis. We
      evaluated the effects of syndecan-1 in various cell-based and animal models of
      lung cancer and found that lung tumorigenesis was moderated by syndecan-1. We
      also demonstrate that syndecan-1 (or lack thereof) alters the miRNA cargo carried
      within exosomes exported from lung cancer cells. Analysis of the changes in miRNA
      expression identified a distinct shift toward augmented procancer signaling
      consistent with the changes found in lung adenocarcinoma. Collectively, our work
      identifies syndecan-1 as an important factor in lung cancer cells that shapes the
      tumor microenvironment through alterations in miRNA packaging within exosomes.

PMID- 29355520
TI  - Impact of capsule endoscopy on prevention of postoperative recurrence of Crohn's
      disease.
AB  - BACKGROUND AND AIMS: Capsule endoscopy (CE) can detect lesions outside the scope
      of ileocolonoscopy in postoperative patients with Crohn's disease (CD). However,
      the impact of such findings on patient outcomes remains unknown. This study is
      intended to evaluate the impact of CE findings on clinical management and
      outcomes in asymptomatic patients with CD without pharmacologic prophylaxis after
      ileocolonic resection. METHODS: In this retrospective cohort study, 37 patients
      (group 1) received ileocolonoscopy together with CE within 1 year after surgery,
      whereas 46 patients (group 2) only received ileocolonoscopy. Patients with
      endoscopic recurrence detected by either ileocolonoscopy or CE received
      pharmacologic therapy with azathioprine or infliximab. One year later, disease
      activity was re-evaluated. RESULTS: In group 1, all patients with ileocolonoscopy
      identified recurrence also had CE-identified recurrence. In addition, CE detected
      endoscopic recurrence in 11 patients missed by ileocolonoscopy. Endoscopic
      remission identified by ileocolonoscopy was confirmed by CE in 13 patients. One
      year later, endoscopic remission identified by ileocolonoscopy was maintained in
      all 24 patients, and none had clinical recurrence. Conversely, in group 2, of
      those with ileocolonoscopy-identified remission, both ileocolonoscopy-identified
      recurrence and clinical recurrence occurred in 9 of 31 patients 1 year later. The
      total clinical recurrence rate was 2.7% (1/37) in group 1 versus 21.7% (10/46) in
      group 2 (P = .019). CONCLUSIONS: If endoscopic remission identified by
      ileocolonoscopy was confirmed by CE, patients could remain free of pharmacologic
      prophylaxis. If recurrence outside the scope of ileocolonoscopy was detected by
      CE, initiation of active pharmacologic therapy would be needed.

PMID- 29355521
TI  - The Dictyostelium GSK3 kinase GlkA coordinates signal relay and chemotaxis in
      response to growth conditions.
AB  - GSK3 plays a central role in orchestrating key biological signaling pathways,
      including cell migration. Here, we identify GlkA as a GSK3 family kinase with
      functions that overlap with and are distinct from those of GskA. We show that
      GlkA, as previously shown for GskA, regulates the cell's cytoskeleton through
      MyoII assembly and control of Ras and Rap1 function, leading to aberrant cell
      migration. However, there are both qualitative and quantitative differences in
      the regulation of Ras and Rap1 and their downstream effectors, including PKB,
      PKBR1, and PI3K, with glkA- cells exhibiting a more severe chemotaxis phenotype
      than gskA- cells. Unexpectedly, the severe glkA- phenotypes, but not those of
      gskA-, are only exhibited when cells are grown attached to a substratum but not
      in suspension, suggesting that GlkA functions as a key kinase of cell attachment
      signaling. Using proteomic iTRAQ analysis we show that there are quantitative
      differences in the pattern of protein expression depending on the growth
      conditions in wild-type cells. We find that GlkA expression affects the cell's
      proteome during vegetative growth and development, with many of these changes
      depending on whether the cells are grown attached to a substratum or in
      suspension. These changes include key cytoskeletal and signaling proteins known
      to be essential for proper chemotaxis and signal relay during the aggregation
      stage of Dictyostelium development.

PMID- 29355522
TI  - sox2 and sox3 cooperate to regulate otic/epibranchial placode induction in
      zebrafish.
AB  - Expression of sox3 is one of the earliest markers of Fgf-dependent
      otic/epibranchial placode induction. We report here that sox2 is also expressed
      in the early otic/epibranchial placode in zebrafish. To address functions of sox2
      and sox3, we generated knockouts and heat shock-inducible transgenes. Mutant
      analysis, and low-level misexpression, showed that sox2 and sox3 act redundantly
      to establish a full complement of otic/epibranchial cells. Disruption of pax8,
      another early regulator, caused similar placodal deficiencies to sox3 mutants or
      pax8-sox3 double mutants, suggesting that sox3 and pax8 operate in the same
      pathway. High-level misexpression of sox2 or sox3 during early stages cell
      autonomously blocked placode induction, whereas misexpression several hours later
      could not reverse placodal differentiation. In an assay for ectopic placode
      induction, we previously showed that misexpression of fgf8 induces a high level
      of ectopic sox3, but not pax8. Partial knockdown of sox3 significantly enhanced
      ectopic induction of pax8, whereas full knockdown of sox3 inhibited this process.
      Together these findings show that sox2 and sox3 are together required for proper
      otic induction, but the level of expression must be tightly regulated to avoid
      suppression of differentiation and maintenance of pluripotency.

PMID- 29355524
TI  - Long non-coding RNA UCA1 promotes lung cancer cell proliferation and migration
      via microRNA-193a/HMGB1 axis.
AB  - Lung cancer is a leading cause of death worldwide. Long non-coding RNAs have been
      documented aberrantly expressed and exerted crucial role in variety of cancers.
      Urothelial carcinoma associated 1 (UCA1) is a potential new type of biomarkers
      for tumor diagnosis and exerts oncogenic effect on various human cancers.
      However, the mechanism of oncogenic role of UCA1 in lung cancer remains unclear.
      In this study, we firstly confirmed the role of UCA1 in lung cancer and found
      that UCA1 down-regulation inhibited cell proliferation and migration in both
      SKMES-1 and H520 lung cancer cells. Then we demonstrated that repressed UCA1
      promoted the miR-193a expression and miR-193a could bind to the predicted binding
      site of UCA1. We then dissected the role of miR-193a in lung cancer and proved
      the anti-tumor role of miR-193a. Furthermore, we found that miR-193a displayed
      its role in lung cancer via modulating the HMGB1 expression. In addition, we
      found that over-expression of HMGB1 could restore the UCA1 knockdown induced
      repression of cell proliferation and migration. In summary, our study
      demonstrated that UCA1 exerts oncogenes activity in lung cancer, acting
      mechanistically by upregulating HMGB1 expression through 'sponging' miR-193a.

PMID- 29355525
TI  - Negative regulation of BRCA1 by transforming acidic coiled-coil protein 3
      (TACC3).
AB  - In spite of the push to identify modifiers of BRCAness, it still remains unclear
      how tumor suppressor BRCA1 is lost in breast cancers in the absence of genetic or
      epigenetic aberrations. Mounting evidence indicates that the transforming acidic
      coiled-coil 3 (TACC3) plays an important role in the centrosome-microtubule
      network during mitosis and gene expression, and that deregulation of TACC3 is
      associated with breast cancer. However, the molecular mechanisms by which TACC3
      contributes to breast cancer development have yet to be elucidated. Herein, we
      found that high levels of TACC3 in human mammary epithelial cells can cause
      genomic instability possibly in part through destabilizing BRCA1. We also found
      that high levels of TACC3 inhibited the interaction between BRCA1 and BARD1, thus
      subsequently allowing the BARD1-uncoupled BRCA1 to be destabilized by ubiquitin
      mediated proteosomal pathway. Moreover, there is an inverse correlation between
      TACC3 and BRCA1 expression in breast cancer tissues. Overall, our findings
      provide a new insight into the role of TACC3 in genomic instability and breast
      tumorigenesis.

PMID- 29355523
TI  - sox2 and sox3 Play unique roles in development of hair cells and neurons in the
      zebrafish inner ear.
AB  - Formation of neural and sensory progenitors in the inner ear requires Sox2 in
      mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2
      and/or Sox3 promote different fates is poorly understood. Our mutant analysis in
      zebrafish showed that sox2 is uniquely required for sensory development while
      sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during
      placodal stages led to development of otic vesicles with expanded sensory and
      reduced neurogenic domains. However, high-level misexpression of sox2 or sox3
      expanded both sensory and neurogenic domains to fill the medial and lateral
      halves of the otic vesicle, respectively. Disruption of medial factor pax2a
      eliminated the ability of sox2/3 misexpression to expand sensory but not
      neurogenic domains. Additionally, mild misexpression of fgf8 during placodal
      development was sufficient to specifically expand the zone of prosensory
      competence. Later, cross-repression between atoh1a and neurog1 helps maintain the
      sensory-neural boundary, but unlike mouse this does not require Notch activity.
      Together, these data show that sox2 and sox3 exhibit intrinsic differences in
      promoting sensory vs. neural competence, but at high levels these factors can
      mimic each other to enhance both states. Regional cofactors like pax2a and fgf8
      also modify sox2/3 functions.

PMID- 29355526
TI  - Piperlongumine and some of its analogs inhibit selectively the human
      immunoproteasome over the constitutive proteasome.
AB  - The natural small molecule piperlongumine A is toxic selectively to cancer cells
      in vitro and in vivo. This toxicity has been correlated with cancer cell ROS, DNA
      damage and apoptotic cell death increases. We demonstrate here a new mechanistic
      property of piperlongumine: it inhibits selectively human immunoproteasome with
      no noticeable inhibition of human constitutive proteasome. This result suggests
      that immunoproteasome inhibition, a mechanism independent of ROS elevation, may
      also partly play a role in the anticancer effects observed with piperlongumine.
      Structure-activity relationships of piperlongumine analogs suggest that the
      lactam (piperidonic) ring of piperlongumine A may be replaced by the linear
      olefin -NHCO-CH2=CH2 to improve both in vitro inhibitory efficiency against
      immunoproteasome and cellular toxicity.

PMID- 29355527
TI  - Isovitexin (IV) induces apoptosis and autophagy in liver cancer cells through
      endoplasmic reticulum stress.
AB  - Liver cancer is a leading cause of cancer death worldwide, and novel
      chemotherapeutic drugs to suppress liver cancer are urgently required. Isovitexin
      (IV), a glycosylflavonoid, is extracted from rice hulls of Oryza sativa, and has
      various biological activities. However, the anti-tumor effect of IV against liver
      cancer has not yet been demonstrated in vitro or in vivo. In the present study,
      we showed that IV significantly suppressed the growth of liver cancer cells.
      Mechanistic studies indicated that IV induced apoptosis by the mitochondrial
      apoptotic pathway, as evidenced by the increase of Bax, cleaved Caspase-3, poly
      (ADP-ribose) polymerase (PARP), and cytoplasm Cyto-c released from mitochondria.
      In addition, IV resulted in autophagy in liver cancer cells, supported by the
      enhancement of LC3II, autophagy-related protein (Atg) 3, Atg5 and Beclin1.
      Suppressing autophagy using bafilomycin A1 (BFA) or siRNA Atg-5 reduced apoptotic
      cells in IV-treated cells, demonstrating that autophagy induction regulated
      apoptosis. Moreover, IV was found to cause endoplasmic reticulum (ER) stress in
      liver cancer cells, along with the promotion of ER stress-related molecules,
      including inositol-requiring enzyme 1alpha (IRE1alpha), X-box-binding protein-1s
      (XBP-1s), C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78.
      Of note, inhibition of ER stress by use of its inhibitor, tauroursodeoxycholate
      (TUDCA), significantly reversed IV-induced apoptosis and autophagy. In vivo, IV
      treatment showed significant tumor growth inhibition compared to the non-treated
      group. IV could therefore be a strong candidate for liver cancer prevention.

PMID- 29355528
TI  - Structural insights into the impact of two holoprosencephaly-related mutations on
      human TGIF1 homeodomain.
AB  - Human protein TGIF1 is an essential regulator of cell fate with broad roles in
      different tissues, and has been implicated in holoprosencephaly (HPE) and many
      cancers. The function of TGIF1 in transcriptional regulation depends on its three
      amino acid loop extension (TALE) type of homeodomain (HD). Two missense mutations
      that led to P192A and R219C substitutions in TGIF1-HD were previously found in
      HPE patients and suggested to be the causes for these cases. However, how these
      mutations affected TGIF1 function has not been investigated from a structural
      view. Here, we investigated the roles of P192 and R219 in TGIF1-HD structure
      packing through determining the NMR structure of TGIF1-HD. Surprisingly, P192 and
      R219 were found to play roles in packing alpha1 and alpha2 to alpha3 together
      with A190 and F215 through side-chain interactions. Circular dichroism (CD)
      showed that P192A and R219C mutants displayed structural change and less folding
      compared with wild-type TGIF1-HD, and 1H-15N HSQC spectrum of P192A mutant
      exhibited chemical shift perturbations in all three helices of TGIF1-HD. Thus, it
      is suggested that P192A and R219C mutations led to structure disturbances of
      TGIF1-HD, which subsequently reduced the DNA-binding affinity of TGIF1-HD by 23
      fold and 10-fold respectively, as revealed by the isothermal titration
      calorimetry (ITC) experiments. Our study provides structural insights of the
      probable pathogenesis mechanism of two TGIF1-related HPE cases, and evidences for
      the roles of P192 and R219 in HD folding.

PMID- 29355529
TI  - An enhanced anti-tumor effect of apoptin-cecropin B on human hepatoma cells by
      using bacterial magnetic particle gene delivery system.
AB  - The gene therapy of cancer, due to the limit of its efficiency and safety, has
      not been widely used in clinical. Recently, bacterial magnetic particles (BMPs),
      which are membrane-bound nanocrystals found in magnetotactic bacteria, have been
      exploited as a new gene delivery system. However, its application on gene therapy
      remains to be explored. In our previous study, we found that a combination of
      cecropin B (ABPs) and apoptin (VP3) could serve as an effective gene therapeutic
      agent. Thus, in this study, we used BMPs to deliver the co-expression plasmid of
      these two gene, namely pVAX1-VA, and evaluated its therapeutic effect on human
      hepatocellular carcinoma (HepG2). Our results showed that BMPs significantly
      improved the efficiency of gene transfection (almost 3-fold than Lipofectamine
      2000 at 48 h, P < .001), which led to stronger apoptosis (in a peak almost 2-fold
      than Lipofectamine 2000-pVAX1-VA, P < .01) and growth inhibition of HepG2 cells.
      More importantly, compared with Lipofectamine 2000-pVAX1-VA group, BMP-pVAX1-VA
      strikingly inhibited tumor growth (0.60 +/- 0.09 g vs. 0.88 +/- 0.11 g, P < .05)
      in nude mouse tumor models and increased the tumor-infiltrating lymphocytes
      considerably without apparent cytotoxicity. These findings suggest that BMPs
      could be an attractive gene delivery system for gene therapy and provide a
      potential available treatment for human hepatocellular carcinoma and maybe some
      other kinds of tumors.

PMID- 29355530
TI  - Spexin as a neuroendocrine signal with emerging functions.
AB  - Spexin (SPX), a novel peptide coevolved with the galanin/kisspeptin family, was
      first identified by bioinformatics prior to its protein purification/functional
      studies. Its mature peptide is highly conserved among different vertebrate
      classes. Based on the studies in mammals and fish models, SPX was found to be
      widely distributed at tissue level, secreted into systemic circulation,
      identified at notable levels in central nervous system and peripheral tissues,
      and has been confirmed/implicated in multiple functions in different
      tissues/organs, suggesting that SPX may serve as a neuroendocrine signal with
      pleotropic functions. In this article, different isoforms of SPX and their
      binding with their cognate receptors GalR2 and GalR3, the biological functions of
      SPX reported in mammals including GI tract movement, energy balance and weight
      loss, fatty acid uptake, glucose homeostasis, nociception and
      cardiovascular/renal functions, as well as the recent findings in fish models
      regarding the role of SPX in reproduction and feeding control will be reviewed
      with interesting questions for future investigations.

PMID- 29355531
TI  - The repeatability of glucocorticoids: A review and meta-analysis.
AB  - Glucocorticoids are highly conserved hormones that mediate a suite of responses
      to changing conditions in vertebrates. Recent work has focused on understanding
      how selection operates on glucocorticoid secretion in natural populations.
      Because heritability is rarely estimated and difficult to measure in the wild,
      many studies report within-individual repeatability as an estimate of stable
      between individual differences in glucocorticoid secretion. We conducted a
      systematic review and meta-analysis on estimates of within-individual
      glucocorticoid repeatability to elucidate general patterns of repeatability, and
      to test for relationships between covariates and estimates of repeatability. To
      this end, we collected 203 estimates of within-individual glucocorticoid
      repeatability drawn from 71 separate studies and 55 species. Overall, we found
      moderate levels of repeatability (0.29). We also found that repeatability varied
      by sample type. Long-term measures (e.g., fecal and feather samples) and acute
      stress-induced plasma glucocorticoids had higher repeatability (long-term: 0.44,
      stress-induced: 0.38), than baseline glucocorticoid levels (0.18). Repeatability
      also decreased with increasing time between repeated sampling events. Despite
      significant overall repeatability, there was substantial heterogeneity in
      estimates from different studies, suggesting that repeatability of glucocorticoid
      secretion varies substantially across systems and conditions. We discuss the
      implications of our results for understanding selection on glucocorticoid traits
      and suggest that continuing work should focus on evaluating the repeatability of
      within-individual glucocorticoid reaction norms.

PMID- 29355532
TI  - Comparative effects of sub-stimulating concentrations of non-human versus human
      Luteinizing Hormones (LH) or chorionic gonadotropins (CG) on adenylate cyclase
      activation by forskolin in MLTC cells.
AB  - We have compared various Luteinizing Hormone (LH) and Chorionic Gonadotropin (CG)
      preparations from non-human and human species in their ability to synergize with
      10 uM forskolin (FSK) for cyclic AMP intracellular accumulation, in MLTC cells.
      LH from rat pituitary as well as various isoforms of pituitary ovine, bovine,
      porcine, equine and human LHs and equine and human CG were studied. In addition,
      recombinant human LH and CG were also compared with the natural human and non
      human hormones. Sub-stimulating concentrations of all LHs and CGs (2-100 pM) were
      found to stimulate cyclic AMP accumulation in MLTC cells in the presence of an
      also non-stimulating FSK concentration (10 uM). Like rat LH, the most homologous
      available hormone for mouse MLTC cells, all non-human LHs and CG exhibit a strong
      potentiating effect on FSK response. The human, natural and recombinant hLH and
      hCG also do so but in addition, they were found to elicit a permissive effect on
      FSK stimulation. Indeed, when incubated alone with MLTC cells at non-stimulating
      concentrations (2-70 pM) hLH and hCG permit, after being removed, a dose
      dependent cyclic AMP accumulation with 10 uM FSK. Our data show a clearcut
      difference between human LH and CG compared to their non-human counterparts on
      MLTC cells adenylate cyclase activity control. This points out the risk of using
      hCG as a reference ligand for LHR in studies using non-human cells.

PMID- 29355533
TI  - Modulatory effect of glutamate GluR2 receptor on the caudal neurosecretory
      Dahlgren cells of the olive flounder, Paralichthys olivaceus.
AB  - A neuromodulatory role for glutamate has been reported for magnocellular
      neuroendocrine cells in mammalian hypothalamus. We examined the potential role of
      glutamate as a local intercellular messenger in the neuroendocrine Dahlgren cell
      population of the caudal neurosecretory system (CNSS) in the euryhaline flounder
      Paralichthys olivaceus. In pharmacological experiments in vitro, glutamate (Glu)
      caused an increase in electrical activity of Dahlgren cells, recruitment of
      previously silent cells, together with a greater proportion of cells showing
      phasic (irregular) activity. The glutamate substrate, glutamine (Gln), led to
      increased firing frequency, cell recruitment and enhanced bursting activity. The
      glutamate effect was not blocked by the N-methyl-D-aspartate (NMDA) receptor
      antagonist MK-801, or the GluR1/GluR3 (AMPA) receptor antagonist IEm1795-2HBr,
      but was blocked by the broad-spectrum alpha-amino-3-hydroxy- 5- methyl-4-isoxazo
      lepropionic acid (AMPA) receptor antagonist ZK200775. Our transcriptome
      sequencing study revealed three AMPA receptor (GluR1, GluR2 and GluR3) in the
      olive flounder CNSS. Quantitative RT-PCR revealed that GluR2 receptor mRNA
      expression was significant increased following dose-dependent superfusion with
      glutamate in the CNSS. GluR1 and GluR3 receptor mRNA expression were decreased
      following superfusion with glutamate. L-type Ca2+ channel mRNA expression had a
      significant dose-dependent decrease following superfusion with glutamate,
      compared to the control. In the salinity challenge experiment, acute transfer
      from SW to FW, GluR2 receptor mRNA expression was significantly higher than the
      control at 2 h. These findings suggest that GluR2 is one of the mechanisms which
      can medicate glutamate action within the CNSS, enhancing electrical activity and
      hence secretory output.

PMID- 29355534
TI  - Neurokinin B signaling in hermaphroditic species, a study of the orange-spotted
      grouper (Epinephelus coioides).
AB  - Neurokinin B (NKB) plays important roles in the mammalian reproductive axis by
      modulating the release of gonadotropin-releasing hormone (GnRH) and
      gonadotropins. In the present study, the tac3 cDNA was cloned from a
      hermaphroditic species, the orange-spotted grouper. Sequence analysis showed that
      the grouper Tac3 precursor encoded two tachykinin peptides, NKB and NKB-related
      peptide (NKBRP). Expression analysis in different tissues revealed that tac3 mRNA
      was highly expressed in the brain of the orange-spotted grouper. In situ
      hybridization further revealed that it was localized in some hypothalamic nuclei
      associated with reproductive regulation. During ovarian development, an increase
      of tac3 expression in the hypothalamus was observed at vitellogenesis stage.
      Intraperitoneal administration of NKB could increase the gnrh1 and lhbeta mRNA
      levels, and enhance the serum estrogen levels, but did not significantly
      influence lhbeta expression in cultured pituitary cells, indicating that NKB does
      not directly exert its actions on the pituitary gland. However, it was found that
      NKBRP had no effect on the expression of two gnrhs and two gths in vivo and in
      vitro. Effects of sex steroids on tac3 expression were further investigated.
      During the 17-methyltestosterone-induced sex change in the orange-spotted
      grouper, hypothalamic tac3 expression showed no significant change.
      Interestingly, ovariectomy greatly stimulated tac3 expression, while the 17beta
      estradiol treatment reversed this effect. In general, our data highly indicated
      that NKB signaling could activate the reproductive axis in the orange-spotted
      grouper. Our study is the first description of the NKB signaling in the
      hermaphroditic species.

PMID- 29355535
TI  - A test of the effects of androgens on immunity: No relationship between 11
      ketotestosterone and immune performance in bluegill (Lepomis macrochirus).
AB  - The immunosuppressive effects of androgens are a key component of the
      immunocompetence handicap hypothesis (ICHH). Here, we use bluegill sunfish
      (Lepomis macrochirus) to test two predictions arising from this hypothesis: (1)
      natural circulating concentrations of the androgen 11-ketotestosterone (11-KT)
      will be negatively related with measures of immunity, and (2) immune stimulation
      will lower circulating 11-KT concentration. We found no evidence for a
      relationship between natural circulating 11-KT concentration and measures of
      immunity (lymphocyte and granulocyte counts, respiratory burst, cytokine mRNA
      levels), and an immune stimulation with Vibrio vaccine did not affect circulating
      11-KT concentration. We also performed a meta-analysis of immune stimulation
      studies to help interpret our results, and report evidence suggesting that immune
      stimulation has weaker effects on androgen levels in fishes compared to other
      vertebrates. These results suggest that the ICHH may not apply to all
      vertebrates, although it remains premature to state what factors account for the
      weaker evidence in fishes that androgens are immunosuppressive.

PMID- 29355536
TI  - A mathematical model of the mevalonate cholesterol biosynthesis pathway.
AB  - We formulate, parameterise and analyse a mathematical model of the mevalonate
      pathway, a key pathway in the synthesis of cholesterol. Of high clinical
      importance, the pathway incorporates rate limiting enzymatic reactions with
      multiple negative feedbacks. In this work we investigate the pathway dynamics and
      demonstrate that rate limiting steps and negative feedbacks within it act in
      concert to tightly regulate intracellular cholesterol levels. Formulated using
      the theory of nonlinear ordinary differential equations and parameterised in the
      context of a hepatocyte, the governing equations are analysed numerically and
      analytically. Sensitivity and mathematical analysis demonstrate the importance of
      the two rate limiting enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and
      squalene synthase in controlling the concentration of substrates within the
      pathway as well as that of cholesterol. The role of individual feedbacks, both
      global (between that of cholesterol and sterol regulatory element-binding protein
      2; SREBP-2) and local internal (between substrates in the pathway) are
      investigated. We find that whilst the cholesterol SREBP-2 feedback regulates the
      overall system dynamics, local feedbacks activate within the pathway to tightly
      regulate the overall cellular cholesterol concentration. The network stability is
      analysed by constructing a reduced model of the full pathway and is shown to
      exhibit one real, stable steady-state. We close by addressing the biological
      question as to how farnesyl-PP levels are affected by CYP51 inhibition, and
      demonstrate that the regulatory mechanisms within the network work in unison to
      ensure they remain bounded.

PMID- 29355537
TI  - Inferring about the extinction of a species using certain and uncertain
      sightings.
AB  - The sighting record of threatened species is often used to infer the possibility
      of extinction. Most of these sightings have uncertain validity. Solow and
      Beet(2014) developed two models using a Bayesian approach which allowed for
      uncertainty in the sighting record by formally incorporating both certain and
      uncertain sightings, but in different ways. Interestingly, the two methods give
      completely different conclusions concerning the extinction of the Ivory-billed
      Woodpecker. We further examined these two methods to provide a mathematical
      explanation, and to explore in more depth, as to why the results differed from
      one another. It was found that the first model was more sensitive to the last
      uncertain sighting, while the second was more sensitive to the last certain
      sighting. The difficulties in choosing the appropriate model are discussed.

PMID- 29355538
TI  - Cooperative "folding transition" in the sequence space facilitates function
      driven evolution of protein families.
AB  - In the protein sequence space, natural proteins form clusters of families which
      are characterized by their unique native folds whereas the great majority of
      random polypeptides are neither clustered nor foldable to unique structures.
      Since a given polypeptide can be either foldable or unfoldable, a kind of
      "folding transition" is expected at the boundary of a protein family in the
      sequence space. By Monte Carlo simulations of a statistical mechanical model of
      protein sequence alignment that coherently incorporates both short-range and long
      range interactions as well as variable-length insertions to reproduce the
      statistics of the multiple sequence alignment of a given protein family, we
      demonstrate the existence of such transition between natural-like sequences and
      random sequences in the sequence subspaces for 15 domain families of various
      folds. The transition was found to be highly cooperative and two-state-like.
      Furthermore, enforcing or suppressing consensus residues on a few of the well
      conserved sites enhanced or diminished, respectively, the natural-like pattern
      formation over the entire sequence. In most families, the key sites included
      ligand binding sites. These results suggest some selective pressure on the key
      residues, such as ligand binding activity, may cooperatively facilitate the
      emergence of a protein family during evolution. From a more practical aspect, the
      present results highlight an essential role of long-range effects in precisely
      defining protein families, which are absent in conventional sequence models.

PMID- 29355539
TI  - The advantage of recombination when selection is acting at many genetic Loci.
AB  - Natural selection can act at many loci across the genome. But as the number of
      polymorphic loci increases linearly, the number of possible genotypic
      combinations increases exponentially. Consequently, a finite population - even a
      very large population - contains only a small sample of all possible multi-locus
      genotypes. In this paper, we revisit the classic Fisher-Muller models of
      recombination, taking into account the abundant standing variation that is
      commonly seen in natural populations. We show that the generation of new
      genotypic combinations through recombination is an important component of
      adaptive evolution based on multi-locus selection. Specifically, high-fitness
      genotypes are expected to be absent from the initial population when the
      frequencies of favorable alleles at the selected loci are low. But as the allele
      frequencies rise in response to selection the missing genotypes will be generated
      by recombination. Given recombination, if the average frequency of the favored
      alleles at the various selected loci is equal to p, then the expected number of
      favorable alleles per chromosome will be equal to pL, where L is the number of
      loci. As the value of p approaches unity at the selected loci, the number of
      favorable alleles per chromosome will approach a value of L, i.e., at the end of
      the selection process a favorable allele will be found at all loci. In the
      absence of recombination, however, selection will be limited to the highest
      fitness genotypes that are already present in the initial population. We point
      out that the fitness of such initial genotypes is far less than the theoretical
      maximum fitness because they contain a favorable allele at only a fraction of the
      loci. Consequently, recombination acts to unblock the adaptive response to multi
      locus selection in finite populations. Using simulations, we show that the sexual
      population can withstand invasion by newly-arising asexual clones. These results
      help explain the maintenance of sexual reproduction in natural populations.

PMID- 29355540
TI  - Intermittent treatment of severe influenza.
AB  - Severe, long-lasting influenza infections are often caused by new strains of the
      virus. The long duration of these infections leads to an increased opportunity
      for the emergence of drug resistant mutants. This is particularly problematic
      since for new strains there is often no vaccine, so drug treatment is the first
      line of defense. One strategy for trying to minimize drug resistance is to apply
      drugs periodically. During treatment phases the wild-type virus decreases, but
      resistant virus might increase; when there is no treatment, wild-type virus will
      hopefully out-compete the resistant virus, driving down the number of resistant
      virus. A stochastic model of severe influenza is combined with a model of drug
      resistance to simulate long-lasting infections and intermittent treatment with
      two types of antivirals: neuraminidase inhibitors, which block release of
      virions; and adamantanes, which block replication of virions. Each drug's ability
      to reduce emergence of drug resistant mutants is investigated. We find that cell
      regeneration is required for successful implementation of intermittent treatment
      and that the optimal cycling parameters change with regeneration rate.

PMID- 29355541
TI  - Discovering the effect of nonlocal payoff calculation on the stabilty of ESS:
      Spatial patterns of Hawk-Dove game in metapopulations.
AB  - The classical idea of evolutionarily stable strategy (ESS) modeling animal
      behavior does not involve any spatial dependence. We considered a spatial Hawk
      Dove game played by animals in a patchy environment with wrap around boundaries.
      We posit that each site contains the same number of individuals. An evolution
      equation for analyzing the stability of the ESS is found as the mean dynamics of
      the classical frequency dependent Moran process coupled via migration and
      nonlocal payoff calculation in 1D and 2D habitats. The linear stability analysis
      of the model is performed and conditions to observe spatial patterns are
      investigated. For the nearest neighbor interactions (including von Neumann and
      Moore neighborhoods in 2D) we concluded that it is possible to destabilize the
      ESS of the game and observe pattern formation when the dispersal rate is small
      enough. We numerically investigate the spatial patterns arising from the
      replicator equations coupled via nearest neighbor payoff calculation and
      dispersal.

PMID- 29355542
TI  - No appendix necessary: Fecal transplants and antibiotics can resolve Clostridium
      difficile infection.
AB  - The appendix has been hypothesized to protect the colon against Clostridium
      difficile infection (CDI) by providing a continuous source of commensal bacteria
      that crowd out the potentially unhealthy bacteria and/or by contributing to
      defensive immune dynamics. Here, a series of deterministic systems comprised of
      ordinary differential equations, which treat the system as an ecological
      community of microorganisms, model the dynamics of colon microbiome. The first
      model includes migration of commensal bacteria from the appendix to the gut,
      while the second model expands this to also include immune dynamics. Simulations
      and simple analytic techniques are used to explore dynamics under biologically
      relevant parameters values. Both models exhibited bistability with steady states
      of a healthy state and of fulminant CDI. However, we find that the appendix size
      was much too small for migration to affect the stability of the system. Both
      models affirm the use of fecal transplants in conjunction with antibiotic use for
      CDI treatment, while the second model also suggests that anti-inflammatory drugs
      may protect against CDI. Ultimately, in general neither the appendiceal migration
      rate of commensal microbiota nor the boost to antibody production could exert an
      appreciable impact on the stability of the system, thus failing to support the
      proposed protective role of the appendix against CDI.

PMID- 29355543
TI  - Modelling the transmission dynamics of two-strain Dengue in the presence
      awareness and vector control.
AB  - In this paper, a mathematical model describing the transmission of two-strain
      Dengue virus between mosquitoes and humans, incorporating vector control and
      awareness of susceptible humans, is proposed. By using the next generation matrix
      method, we obtain the threshold values to identify the existence and stability of
      three equilibria states, that is, a disease-free state, a state where only one
      serotype is present and another state where both serotypes coexist. Further,
      explicit conditions determining the persistence of this disease are also
      obtained. In addition, we investigate the sensitivity analysis of threshold
      conditions and the optimal control strategy for this disease. Theoretical results
      and numerical simulations suggest that the measures of enhancing awareness of the
      infected and susceptible human self-protection should be taken and the mosquito
      control measure is necessary in order to prevent the transmission of Dengue virus
      from mosquitoes to humans.

PMID- 29355545
TI  - The urinary excretion of metformin, ceftizoxime and ofloxacin in high serum
      creatinine rats: Can creatinine predict renal tubular elimination?
AB  - The renal excretion of creatinine and most drugs are the net result of glomerular
      filtration and tubular secretion, and their tubular secretions are mediated by
      individual transporters. Thus, we hypothesized that the increase of serum
      creatinine (SCr) levels attributing to inhibiting tubular transporters but not
      glomerular filtration rate (GFR) could be used to evaluate the tubular excretion
      of drugs mediated by identical or partial overlap transporter with creatinine. In
      this work, we firstly developed the creatinine excretion inhibition model with
      normal GFR by competitively inhibiting tubular transporters, and investigated the
      renal excretion of metformin, ceftizoxime and ofloxacin in vivo and in vitro. The
      results showed that the 24-hour urinary excretion of metformin and ceftizoxime in
      model rats were decreased by 25% and 17% compared to that in control rats,
      respectively. The uptake amount and urinary excretion of metformin and
      ceftizoxime could be inhibited by creatinine in renal cortical slices and
      isolated kidney perfusion. However, the urinary excretion of ofloxacin was not
      affected by high SCr. These results showed that the inhibition of tubular
      creatinine transporters by high SCr resulted to the decrease of urinary excretion
      of metformin and ceftizoxime, but not ofloxacin, which implied that the increase
      of SCr could also be used to evaluate the tubular excretion of drugs mediated by
      identical or partial overlap transporter with creatinine in normal GFR rats.

PMID- 29355544
TI  - Quercetin suppresses breast cancer stem cells (CD44+/CD24-) by inhibiting the
      PI3K/Akt/mTOR-signaling pathway.
AB  - AIMS: Cancer stem cells (CSCs) are considered the prime source of cancer
      recurrence, metastasis, and progression and represent important targets for
      developing novel anticancer agents and therapeutic strategies. The aim of this
      study was to investigate the effect of treating breast CSCs with the anticancer
      flavonoid, quercetin. MAIN METHODS: We examined changes in the cluster of
      differentiation CD44+/CD24-CSC population and behavior using the breast cancer
      cell line MCF-7. KEY FINDINGS: Our results indicated that cell viability, clone
      formation, mammosphere generation, and nude mice tumor metastasis were inhibited
      in the CD44+/CD24- population and that MCF-7 cells exhibited G1-phase arrest
      after quercetin treatment. Additionally, CyclinD1 and B cell lymphoma-2
      expression were suppressed and Bcl-2-like protein-4 expression was enhanced after
      quercetin treatment. We also observed that estrogen receptor alpha and
      phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR)
      signaling were downregulated concurrently with the inhibition of CD44+/CD24-
      viability and clone formation. Our findings suggested that quercetin treatment
      promoted weaker malignant activity associated with CSCs relative to that observed
      in normal cancer cells through its inhibition of the PI3K/Akt/mTOR-signaling
      pathway. SIGNIFICANCE: These results indicated that CSCs are potential
      therapeutic targets for quercetin treatment of breast cancer.

PMID- 29355546
TI  - Magnolol treatment attenuates dextran sulphate sodium-induced murine experimental
      colitis by regulating inflammation and mucosal damage.
AB  - Magnolol, the main and active ingredient of the Magnolia officinalis, has been
      widely used in traditional prescription to the human disorders. Magnolol has been
      proved to have several pharmacological properties including anti-bacterial, anti
      oxidant and anti-inflammatory activities. However, the effects of magnolol on
      ulcerative colitis (UC) have not been reported. The aim of this study was to
      investigate the protective effects and mechanisms of magnolol on dextran sulphate
      sodium (DSS)-induced colitis in mice. The results showed that magnolol
      significantly alleviated DSS-induced body weight loss, disease activities index
      (DAI), colon length shortening and colonic pathological damage. In addition,
      magnolol restrained the expression of TNF-alpha, IL-1beta and IL-12 via the
      regulation of nuclear factor-kappaB (NF-kappaB) and Peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) pathways. Magnolol also enhanced the
      expression of ZO-1 and occludin in DSS-induced mice colonic tissues. These
      results showed that magnolol played protective effects on DSS-induced colitis and
      may be an alternative therapeutic reagent for colitis treatment.

PMID- 29355547
TI  - beta-Blockers in COPD: A Cohort Study From the TONADO Research Program.
AB  - BACKGROUND: Cardiovascular disease is a frequent comorbidity in patients with
      COPD. Many physicians, particularly pulmonologists, are reluctant to use beta
      adrenoceptor blocking agents (beta-blockers) in patients with COPD, despite their
      proven effectiveness in preventing cardiovascular events. METHODS: The large
      (5,162 patients) phase III TONADO 1 and 2 studies assessed lung function and
      patient-reported outcomes in patients with moderate to very severe COPD receiving
      long-acting bronchodilator treatment across 1 year. This post hoc analysis
      characterized lung-function changes, patient-reported outcomes, and safety in the
      subgroup of patients receiving beta-blockers in the studies. RESULTS: In total,
      557 of 5,162 patients (11%) received beta-blockers at baseline.
      Postbronchodilator FEV1 at baseline was higher in the beta-blocker group (1.470
      L) compared with that in the no beta-blocker group (1.362 L). As expected,
      patients receiving beta-blockers had a more frequent history of cardiovascular
      comorbidities and medications. Lung function improved from baseline in patients
      with or those without beta-blocker treatment, and no relevant between-group
      differences were observed in trough FEV1 or trough FVC at 24 or 52 weeks. No
      relevant differences were observed for St. George's Respiratory Questionnaire
      results and Transition Dyspnea Index in patients with beta-blockers compared with
      those in patients without. Safety findings were comparable between groups.
      CONCLUSIONS: Lung function, overall respiratory status, and safety of
      tiotropium/olodaterol were not influenced by baseline beta-blocker treatment in
      patients with moderate to very severe COPD. Results from this large patient
      cohort support the cautious and appropriate use of beta-blockers in patients with
      COPD and cardiovascular comorbidity. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01431274 and No. NCT01431287; URL: www.clinicaltrials.gov.

PMID- 29355548
TI  - Treating Cough Due to Non-CF and CF Bronchiectasis With Nonpharmacological Airway
      Clearance: CHEST Expert Panel Report.
AB  - BACKGROUND: In bronchiectasis due to cystic fibrosis (CF) and other causes,
      airway clearance is one of the mainstays of management. We conducted a systematic
      review on airway clearance by using non-pharmacological methods as recommended by
      international guidelines to develop recommendations or suggestions to update the
      2006 CHEST guideline on cough. METHODS: The systematic search for evidence
      examined the question, "Is there evidence of clinically important treatment
      effects for non-pharmacological therapies in cough treatment for patients with
      bronchiectasis?" Populations selected were all patients with bronchiectasis due
      to CF or non-CF bronchiectasis. The interventions explored were the non
      pharmacological airway clearance therapies. The comparison populations included
      those receiving standard therapy and/or placebo. Clinically important outcomes
      that were explored were exacerbation rates, quality of life, hospitalizations,
      and mortality. RESULTS: In both CF and non-CF bronchiectasis, there were
      systematic reviews and overviews of systematic reviews identified. Despite these
      findings, there were no large randomized controlled trials that explored the
      impact of airway clearance on exacerbation rates, quality of life,
      hospitalizations, or mortality. CONCLUSIONS: Although the cough panel was not
      able to make recommendations, they have made consensus-based suggestions and
      provided direction for future studies to fill the gaps in knowledge.

PMID- 29355549
TI  - Air Pollution Exposure Is Associated With Lower Lung Function, but Not Changes in
      Lung Function, in Patients With Idiopathic Pulmonary Fibrosis.
AB  - BACKGROUND: Air pollution exposure is associated with acute exacerbation, disease
      progression, and mortality in patients with idiopathic pulmonary fibrosis (IPF).
      The objective of this study was to describe the impact of air pollution exposures
      on disease severity, as well as changes in lung function, in patients with IPF.
      METHODS: Using home spirometers and symptom diaries, 25 patients with IPF
      prospectively recorded FVC weekly for up to 40 weeks. Residential addresses were
      geocoded to estimate weekly mean air pollution exposures for ground-level ozone
      (O3), nitrogen dioxide (NO2), and particulate matter < 2.5 or 10 MUm in
      aerodynamic diameter (PM2.5 and PM10, respectively). The dependence of weekly
      clinical measurements on preceding levels of each pollutant was assessed with the
      use of linear mixed models, yielding beta-coefficients with 95% CIs, using
      varying lag times. RESULTS: Lower mean FVC % predicted was consistently
      associated with increased mean exposures to PM10 in the 2 to 5 weeks preceding
      clinical measurements (range, -0.46 to -0.39 [95% CI, -0.73 to -0.13]; P < .005).
      Lower mean FVC % predicted over the study period was inversely related to mean
      levels of NO2 (-0.45 [95% CI, -0.85 to -0.05]; P = .03), PM2.5 (-0.45 [95% CI, 
      0.84 to -0.07]; P = .02), and PM10 (-0.57 [95% CI, -0.92 to -0.21]; P = .003),
      averaged over the study. Weekly changes in FVC and changes over 40 weeks were
      independent of pollution exposures. CONCLUSIONS: Higher air pollution exposures
      were associated with lower lung function, but not changes in lung function, in
      patients with IPF. Further studies are needed to characterize the mechanisms
      underlying this relationship.

PMID- 29355550
TI  - Research in Extracorporeal Life Support: A Call to Action.

PMID- 29355551
TI  - Baseline and Serial Brain Natriuretic Peptide Level Predicts 5-Year Overall
      Survival in Patients With Pulmonary Arterial Hypertension: Data From the REVEAL
      Registry.
AB  - BACKGROUND: Plasma brain natriuretic peptide (BNP) level is a prognostic
      biomarker in pulmonary arterial hypertension (PAH). Its impact on long-term
      overall survival (OS) was investigated in the Registry to Evaluate Early and Long
      term Pulmonary Arterial Hypertension Disease Management (REVEAL), a 5-year
      observational, multicenter, US registry of patients with PAH. METHODS: Patients
      were >= 18 years of age, met right heart catheterization criteria at rest, had
      World Health Organization group I PAH, and had BNP measurement at enrollment.
      Optimal BNP threshold was obtained via receiver operating characteristic curve
      analysis. OS was compared in patients with low (<= 340 pg/mL) vs high (> 340
      pg/mL) BNP at baseline; changes between baseline and last assessment were also
      examined. Patients were categorized based on baseline (low or high) and follow-up
      (low or high) BNP values; hazard ratios (HRs) for OS were estimated and compared
      using Cox regression. RESULTS: Overall, 1,426 patients were analyzed. Mortality
      risk was significantly higher in patients with baseline high vs low BNP (HR, 3.6;
      95% CI, 3.0-4.2). BNP change analysis at <= 1 year postenrollment demonstrated
      that the low-low group had the lowest and the high-high group had the highest 5
      year mortality risk (HR, 0.23; 95% CI, 0.19-0.27). Changes in BNP score also
      correlated with change of risk of death. CONCLUSIONS: Baseline BNP threshold of
      340 pg/mL strongly predicted survival up to 5 years in patients with PAH. A BNP
      reduction at 1 year since enrollment was associated with decreased mortality
      risk, whereas an increase in BNP at 1 year was associated with an increased
      mortality risk, supporting BNP as a surrogate marker of PAH survival.

PMID- 29355552
TI  - Maternal hypertension and feto-placental growth restriction is reversed by
      sildenafil: Evidence of independent effects of circulating nitric oxide levels.
AB  - Sildenafil has shown nitric oxide (NO)-independent pleiotropic effects, however
      the mechanisms involved are unclear. We investigated the protective effects of
      sildenafil against hypertension in pregnancy and feto-placental growth
      restriction induced by NO inhibition, and if sodium nitrite-derived NO formation
      influences sildenafil effects. We evaluated the plasmatic levels of NO
      metabolites, cyclic guanosine monophosphate (cGMP), oxidative stress and
      myeloperoxidase, which are involved in endothelial dysfunction during
      hypertension in pregnancy. Also, we performed in vitro experiments to examine
      cell viability and NO synthesis in human umbilical vein endothelial cells
      (HUVECs) cultures incubated with plasma from healthy or hypertensive pregnant
      rats treated (or not) with both drugs, either alone or in association. Sildenafil
      blunted hypertension in pregnancy and protected against feto-placental growth
      restriction induced by NO inhibition and these effects of sildenafil alone were
      similar to those presented by its association with sodium nitrite. Protective
      effects of sildenafil were observed even with low plasmatic NO levels and were
      not followed by increases in cGMP levels. Also, sildenafil, but not sodium
      nitrite, blunted the increases in myeloperoxidase activity. Both drugs (isolated
      or in association) presented antioxidant effects. Plasma from hypertensive
      pregnant rats treated with sildenafil, but not sodium nitrite alone, increased
      the viability of HUVECs. NO synthesis in HUVECs cultures was increased with
      plasma from rats treated with both drugs. We conclude that sildenafil effects are
      not dependent of circulating NO levels in hypertension and feto-placental growth
      restriction. These findings may reflect a protection against myeloperoxidase and
      pro-oxidant activation in hypertension in pregnancy.

PMID- 29355553
TI  - New application of the commercial sweetener rebaudioside a as a hepatoprotective
      candidate: Induction of the Nrf2 signaling pathway.
AB  - A large population of drug candidates have failed "from bench to bed" due to
      unwanted toxicities. We intend to develop an alternative approach for drug
      discovery, that is, to seek candidates from "safe" compounds. Rebaudioside A (Reb
      A) is an approved commercial sweetener from Stevia rebaudiana Bertoni. We found
      that Reb-A protects against carbon tetrachloride (CCl4)-induced oxidative injury
      in human liver hepatocellular carcinoma (HepG2) cells. Reb-A showed antioxidant
      activity on reducing cellular reactive oxygen species and malondialdehyde levels
      while increasing glutathione levels and superoxide dismutase and catalase
      activities. Reb-A treatment induced nuclear factor erythroid-derived 2-like 2
      (Nrf2) activation and antioxidant response element activity, as well as the
      expression of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1
      (NQO1). Further mechanistic studies indicated that c-Jun N-terminal kinase (JNK),
      extracellular signal-regulated protein kinase (ERK), mitogen-active protein
      kinase (MAPK) and protein kinase C epsilon (PKCepsilon) signaling was
      upregulated. Thus, the present in vitro study conclusively demonstrated that Reb
      A is an activator of Nrf2 and is a potential candidate hepatoprotective agent.
      More importantly, the present study illustrated that seeking drug candidates from
      "safe" compounds is a promising strategy.

PMID- 29355554
TI  - Dual inhibition of HY023016 based on binding properties of platelet membrane
      receptor subunit glycoprotein Ibalpha and thrombin exosites.
AB  - Thrombin has long been suggested as a desirable antithrombotic target, but anti
      thrombin therapy without anti-platelet thereby has never achieved the ideal
      effect. HY023016 is a novel compound, in our previous study, it exerted better
      anti-thrombotic than dabigatran etexilate. The present study aims to illustrate
      the excess anti-thrombotic molecular mechanisms of HY023016 through thrombin
      anion exosites and the platelet membrane receptor subunit glycoprotein Ibalpha
      (GPIbalpha). HY023016 strongly inhibited the conversion of fibrinogen to fibrous
      may via blocking thrombin exosite I. We also discovered that HY023016 remarkably
      inhibited exosite II by a loss of affinity for the gamma'-peptide of fibrinogen
      and for heparin. Furthermore, a solid phase binding assay revealed that HY023016
      inhibited ristocetin-induced washed platelets bind to von Willebrand factor
      (vWF). In GST pull-down assay, HY023016 decreased the binding of recombinant vWF
      A1 to GPIbalpha N-terminal. Thus, HY023016 provides an innovative idea for
      designing multi-targeted anti-thrombotic drugs and laying a scientific foundation
      for reducing "total thrombosis risk" in a clinical drug treatment.

PMID- 29355555
TI  - Phosphodiesterase-3 inhibitor cilostazol reverses endothelial dysfunction with
      ageing in rat mesenteric resistance arteries.
AB  - Ageing impairs endothelial function, which is considered a hallmark of the
      development of cardiovascular diseases in elderly. Cilostazol, a
      phosphodiesterase-3 inhibitor, has antiplatelet, antithrombotic and protective
      effects on endothelial cells. Here, we hypothesized that cilostazol could improve
      endothelial function in mesenteric resistance arteries (MRA) from old rats. Using
      eight-week cilostazol-treated (100mg/kg/day) or untreated 72-week-old Wistar
      rats, we evaluate the relaxation to acetylcholine, sodium nitroprusside (SNP),
      forskolin and isoproterenol and the noradrenaline-induced contraction in MRA.
      Superoxide anion and nitric oxide (NO) was measured by dihydroethidium- and
      diaminofluorescein-2-emitted fluorescence, respectively. Normotensive old rats
      had impaired acetylcholine-induced NO- and EDHF-mediated relaxation and increased
      noradrenaline vasoconstriction than young rats. This age-associated endothelial
      dysfunction was restored by cilostazol treatment. Relaxation to SNP, forskolin or
      isoproterenol remained unmodified by cilostazol. Diaminofluorescein-2-emitted
      fluorescence was increased while dihydroethidium-emitted was decreased by
      cilostazol, indicating increased NO and reduced superoxide generation,
      respectively. Cilostazol improves endothelial function in old MRA without
      affecting blood pressure. This protective effect of cilostazol could be
      attributed to reduced oxidative stress, increased NO bioavailability and EDHF
      type relaxation. Although these results are preliminary, we believe that should
      stimulate further interest in cilostazol as an alternative for the treatment of
      age-related vascular disorders.

PMID- 29355556
TI  - Chrysin reverses the depressive-like behavior induced by hypothyroidism in female
      mice by regulating hippocampal serotonin and dopamine.
AB  - Hypothyroidism is often associated with psychiatric disorders such as depression.
      In this study, we evaluated the effect of chrysin on depressive-like behavior and
      monoamine levels in hypothyroid female mice. Hypothyroidism was induced by
      continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days.
      Exposure to MTZ was associated with low plasma levels of thyroid hormones T3 and
      T4 compared with the control group. Subsequently, euthyroid and MTZ-induced
      hypothyroid mice were intragastrically administered vehicle or chrysin (20mg/kg)
      once a day for 28 consecutive days. After treatments, the following behavioral
      assessments were performed: Open-Field Test (OFT), Tail suspension test (TST),
      and Forced Swimming Test (FST). Additionally, T3 and T4 levels were measured
      again, and serotonin (5HT), dopamine, and noradrenaline levels were analyzed in
      the prefrontal cortex and the hippocampus. Chrysin treatment could not reverse T3
      and T4 levels. Hypothyroid mice showed an increased immobility time in TST and
      FST; chrysin treatment reversed these effects. Reduced levels of 5HT and dopamine
      in the prefrontal cortex and the hippocampus were observed in the hypothyroid
      mice than in the euthyroid mice. Chrysin treatment recovered 5HT content in both
      structures and dopamine content only in the hippocampus. Noradrenaline content
      was not altered by treatments. Together, our results have demonstrated that
      chrysin treatment reverses depressive-like behaviors in hypothyroid female mice
      and suggests the involvement of 5HT and dopamine in these effects.

PMID- 29355557
TI  - Blockage of endoplasmic reticulum stress attenuates nilotinib-induced
      cardiotoxicity by inhibition of the Akt-GSK3beta-Nox4 signaling.
AB  - Cardiotoxicity is a critical side-effect of nilotinib during treatment for
      cancer, such as chronic myeloid leukemia, while the potential signaling
      mechanisms remain unclear. The role of and the relationship between endoplasmic
      reticulum (ER) stress and mitochondrial dysfunction was investigated in nilotinib
      induced cardiac H9C2 injury as a suitable cell model. Our results showed that ER
      stress was persistently induced in nilotinib-treated cells, evidenced by increase
      of GRP78, CHOP, ATF4 and XBP1 as well as phospho-PERKThr980. The results from 4
      phenylbutyrate (PBA, an ER stress inhibitor) and SC79 (a specific Akt activator)
      suggested that ER stress increased activity of glycogen synthase kinase-3 beta
      (GSK3beta) that is reflected by decrease of phospho-GSK3betaSer9, through
      downregulation of phospho-AktSer473, and that prolonged ER stress and activated
      GSK3beta involved nilotinib-induced apoptosis. In addition, the data from JNK
      inhibition using SP600125 showed that over-activated JNK was responsible for Akt
      de-phosphorylation. Moreover, the abundance of NADPH oxidase (Nox4) was
      significantly increased following nilotinib treatment, which was prevented by
      SB216763 (a specific GSK3beta inhibitor). Additionally, mitochondrial dysfunction
      was indicated by reduced mitochondrial membrane potential (MMP) level and
      increased reactive oxygen species level. In nilotinib-treated cells, knockdown of
      Nox4 preserved MMP level, abrogated reactive oxygen species production, and
      decreased apoptosis. Accordingly, our data demonstrated that inhibition of ER
      stress may protect cardiomyocytes against nilotinib toxicity potentially through
      inactivation of Akt-GSK3beta-Nox4 signaling. These findings may provide an
      attractive therapeutic target for treatment of nilotinib-related cardiotoxicity.

PMID- 29355558
TI  - (-)-Epicatechin stimulates mitochondrial biogenesis and cell growth in C2C12
      myotubes via the G-protein coupled estrogen receptor.
AB  - We have reported on the capacity of (-)-epicatechin ((-)-EPI) to stimulate
      mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the
      mechanisms mediating the effects of (-)-EPI are not fully understood. We
      previously identified a role of the G-protein coupled estrogen receptor (GPER) in
      modulating the vascular effects of (-)-EPI. We therefore tested the hypothesis
      that GPER mediates (at least in part) the stimulatory effects of (-)-EPI on MiB
      in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts
      differentiated into myotubes. Using confocal microscopy, we detected GPER at the
      cell surface and cytoplasm in C2C12 myotubes. Treatment with (-)-EPI (3 and
      10MUM) resulted in the stimulation of MiB as per increases in mitochondrial inner
      (MitoTracker Red FM fluorescence staining) and outer membrane (porin protein
      levels) markers, transcription factors involved in MiB stimulation (i.e., nuclear
      respiratory factor-2 [NRF-2] and mitochondrial transcription factor A [TFAM]
      protein levels) and citrate synthase (CS) activity levels. (-)-EPI-treated
      myotubes were longer and wider compared to vehicle-treated myotubes. The effects
      of (-)-EPI on myotube mitochondria and cell size were larger in magnitude to
      those observed with the GPER agonist G-1. The chemical blockade and down
      regulation (siRNA) of GPER evidenced a partial and complete blockade of measured
      endpoints following (-)-EPI- or G-1-treatment, respectively. Altogether, results
      indicate that GPER is expressed in muscle cells and appears to mediate to a
      significant extent, the stimulatory effects of (-)-EPI on MiB. Thus, GPER
      activation may account for the stimulatory effects of (-)-EPI on SkM
      structure/function.

PMID- 29355559
TI  - Evaluation of pharmacokinetics/pharmacodynamics and efficacy of one-month depots
      of TAK-448 and TAK-683, investigational kisspeptin analogs, in male rats and an
      androgen-dependent prostate cancer model.
AB  - TAK-448 and TAK-683 are kisspeptin agonist analogs with improved in vivo
      stability and activity. Previous studies showed that continuous subcutaneous
      administration of TAK-448 or TAK-683 caused rapid and profound reductions in
      plasma testosterone levels in various species, including male healthy volunteers,
      suggesting their therapeutic potential as anti-prostate cancer agents. For
      clinical drug development, one-month sustained-release depots of TAK-448 and TAK
      683, TAK-448-SR(1M) and TAK-683-SR(1M), were designed to improve usability in
      clinical practice. In this study, the pharmacokinetics/pharmacodynamics (PK/PD)
      profiles of TAK-448-SR(1M) and TAK-683-SR(1M) were initially tested in male rats
      to ensure their eligibility as one-month depots. The therapeutic advantages of
      TAK-448-SR(1M) and TAK-683-SR(1M) over TAP-144-SR(1M) were then investigated in a
      JDCaP xenograft rat model. TAK-448-SR(1M) and TAK-683-SR(1M) maintained certain
      levels of plasma TAK-448 free form (TAK-448F) and plasma TAK-683 free form (TAK
      683F) for at least 4 weeks, before clearance from the circulation. Accompanying
      their desirable PK profiles, TAK-448-SR(1M) and TAK-683-SR(1M) showed favorable
      PD responses as one-month depots and demonstrated better testosterone control
      than TAP-144-SR(1M). Both depots exerted rapid and profound suppression of plasma
      testosterone levels in male rats. These profound suppressive effects were
      maintained in dose-dependent manners, before recovery toward normal levels. In
      the JDCaP xenograft model, TAK-448-SR(1M) and TAK-683-SR(1M) both showed better
      prostate-specific antigen (PSA) control than TAP-144-SR(1M), although all
      treatment groups eventually experienced PSA recurrence and tumor regrowth. In
      conclusion, this study demonstrates that both TAK-448-SR(1M) and TAK-683-SR(1M)
      have desirable and better PK/PD profiles than TAP-144-SR(1M) in rats, which could
      potentially provide better clinical outcomes in androgen-dependent prostate
      cancer.

PMID- 29355560
TI  - miR-671 promotes prostate cancer cell proliferation by targeting tumor suppressor
      SOX6.
AB  - Prostate cancer is one of the most severe malignancies in men, and many genes and
      non-coding RNAs, included microRNAs (miRs), have been demonstrated to regulate
      prostate cancer progression. In the present study, we investigated the role of
      miR-671 in prostate cancer cell proliferation. We found that miR-671 was
      significantly upregulated in human prostate cancer tissues and cells. miR-671
      overexpression promoted prostate cancer cell proliferation, while its
      downregulation inhibited prostate cancer cell proliferation, as determined by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, colony
      formation assays, soft agar growth assays, and bromodeoxyuridine (BrdU)
      incorporation assays. miR-671 directly targets the 3' untranslated region (UTR)
      of the tumor suppressor SOX6 (encoding SRY (sex determining region Y)-box 6) to
      inhibit its expression. Double knockdown of miR-671 and SOX6 promoted PC3 cell
      proliferation, suggesting that miR-671 promotes prostate cancer cell
      proliferation by inhibiting SOX6.

PMID- 29355561
TI  - Ameliorating effects of D-47, a newly developed compound, on lipid metabolism in
      an animal model of familial hypercholesterolemia (WHHLMI rabbits).
AB  - Improvements induced in lipid metabolism in the liver by D-47, a newly developed
      compound, were examined herein. WHHLMI rabbits, an animal model of
      hypercholesterolemia and coronary atherosclerosis, was fed D-47-supplemented chow
      for 5 weeks at a dose of 30mg/kg. Lipid concentration were assayed using
      enzymatic methods. Plasma lipoproteins were fractionated with an ultracentrifuge.
      mRNA expression was analyzed with real-time PCR. Lipidome analyses of
      lipoproteins were performed using supercritical fluid chromatography mass
      spectrometry. In the D-47-treated group, serum lipid levels decreased by 23% for
      total cholesterol and by 40% for triglycerides. These reductions were mainly
      attributed to decreases in the VLDL fraction. Compared with the control, in the D
      47 group, lipid contents in the liver were decreased by 22% in cholesterol and by
      69% in triglycerides, and fat accumulation was decreased by 57% in pericardial
      fat and by 17% in mesenteric fat. In lipidome analyses of VLDL fraction,
      lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylinositol, phosphatidylethanolamine plasmalogen, sphingomyelin, and
      ceramide were decreased by the D-47 treatment. mRNA expression in the liver was
      51% lower for FAS and 24% lower for MTP, but 5.9- and 5.1-fold higher for CYP7A1
      and CPT-1, respectively, in the D-47 group than in the control. mRNA expression
      was 72%, 64%, and 36% higher for LPL, CTP-1, and PPARgamma, respectively, in
      mesenteric fat in the D-47 group. D-47 is a potent lipid-lowering compound that
      uses a different mechanism of action from that of statins. It has potential as a
      compound in the treatment of steatohepatitis and metabolic syndrome.

PMID- 29355562
TI  - Cilostazol attenuates indices of liver damage induced by thioacetamide in albino
      rats through regulating inflammatory cytokines and apoptotic biomarkers.
AB  - Even though cilostazol was assessed before in several models of atherosclerosis,
      so far its full systematic effect as a natural anti-inflammatory and anti
      apoptotic mediator in the protection of liver damage and complication has not
      been fully clarified, which is the target of this study. For that purpose, we
      examined the protective effect of cilostazol (10 and 5mg/kg, p.o. b.wt.) in an
      acute hepatic injury model by orally injecting it for 3 weeks prior to a single
      dose of TAA (300mg/kg, i.p) injection. Ursodeoxycholic acid was used as a
      standard drug (50mg/kg, p.o. b.wt.). After injection of thioacetamide by 48hr,
      rats were sacrificed. On the serum biochemical level, cilostazol ameliorated the
      thioacetamide consequence, where it presented a significant enhancement in the
      liver enzymes activities [Aspartate aminotransferase (AST) & Alanine
      aminotransferase (ALT)]. On the other hand, at the tissue level (Liver), it
      revealed a significant improvement in pro-inflammatory cytokines [Tumor necrosis
      factor alpha (TNF-alpha), Interleukin 1 beta (IL-1beta), Nuclear factor kappa B
      (NF-kappaB), NF-kappaB (P65/P50 nucleus translocation), caspase-3, cleaved
      caspase-3 & C-reactive protein (CRP)], redox level [Reduced glutathione (GSH) &
      Malondialdehyde (MDA)], histopathological findings, Reverse transcription
      polymerase chain reaction (RT-PCR) analysis (expression of TNF-alpha and NF
      kappaB mRNA levels), and immunohistochemical reaction (caspase-3 & TNF-alpha).
      Obviously, the high dose of cilostazol (10mg/kg, p.o. b.wt.) displayed a more
      pronounced effect than its lower one and nearly equal to ursodeoxycholic acid in
      the most of the parameters. These results give a new awareness into the hopeful
      molecular mechanisms by which cilostazol attenuates several factors participated
      in the progression of liver damage.

PMID- 29355564
TI  - Three new withanolides from the calyces of Nicandra physaloides.
AB  - Chemical investigation on ethyl acetate extract of the calyces of Nicandra
      physaloides resulted in the isolation of three new withanolides named as
      nicphysatone A (1), nicphysatone B (2), nicphysatone C (3), together with five
      known withanolides, nic 17 (4), nic 7 (5), nic 2 (6), withahisolide G (7) and
      nicaphysalin B (8). The structures were determined by comprehensive spectroscopic
      experiments. The discovery enriched the diversity of natural withanolides and
      could serve as scaffolds for the synthesis of more potent modified withanolides.

PMID- 29355563
TI  - Taraxerol as a possible therapeutic agent on memory impairments and Alzheimer's
      disease: Effects against scopolamine and streptozotocin-induced cognitive
      dysfunctions.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder associated with
      cognitive impairment and cholinergic neuronal death, characteristic of the effect
      of time on biochemical neuronal function. The use of medicinal plants as an
      alternative form of prevention, or even as a possible treatment of AD, is
      therefore interesting areas of research, since the standard drugs have many side
      effects. Taraxerol (TRX) is a triterpene that has been isolated from several
      plant species, and its various pharmacological properties have already been
      identified, such the acetylcholinesterase (AChE) inhibition activity in vitro.
      There is a lack of information in literature that confirms the effect of TRX in
      an animal AD-like model. Seeking to fill this gap in the literature, in the
      present work we assessed the effect of TRX on AChE activity in the animals'
      encephalon and hippocampus. We also investigated the effect of TRX (1.77 uM/side,
      0.5 MUL) isolated from leaves of Eugenia umbelliflora Berg. on aversive memory
      impairments induced by scopolamine (2 ug/side, 0.5 uL) infused into rat
      hippocampus, and the effect of TRX (0.89 and 1.77 uM/side, 0.5 MUL) on aversive
      memory impairments induced by streptozotocin (STZ) (2.5 mg/mL, 2.0 uL) infused
      i.c.v. into mice, using the step-down inhibitory avoidance task. We found that
      TRX significantly inhibited AChE activity in the animal's hippocampus.
      Furthermore, TRX significantly improved scopolamine and STZ-induced memory
      impairment. Taking together, these results confirms its AChE activity inhibition
      in animals and indicate that TRX has anti-amnesic activity that may hold
      significant therapeutic value in alleviating certain memory impairments observed
      in AD.

PMID- 29355565
TI  - Effects of background and contour luminance on the hue and brightness of the
      Watercolor effect.
AB  - Conjoint measurement was used to investigate the joint influences of the
      luminance of the background and the inner contour on hue- and brightness filling
      in for a stimulus configuration generating a water-color effect (WCE), i.e., a
      wiggly bi-chromatic contour enclosing a region with the lower luminance component
      on the exterior. Two stimuli with the background and inner contour luminances
      covarying independently were successively presented, and in separate experiments,
      the observer judged which member of the pair's interior regions contained a
      stronger hue or was brighter. Braided-contour control stimuli that generated
      little or no perceptual filling-in were also used to assess whether observers
      were judging the interior regions and not the contours themselves. Three nested
      models of the contributions of the background and inner contour to the judgments
      were fit to the data by maximum likelihood and evaluated by likelihood ratio
      tests. Both stimulus components contributed to both the hue and brightness of the
      interior region with increasing luminance of the inner contour generating an
      assimilative filling-in for the hue judgments but a contrast effect for the
      brightness judgments. Control analyses showed negligible effects for the order of
      the luminance of the background or inner contour on the judgments. An additive
      contribution of both components was rejected in favor of a saturated model in
      which the responses depended on the levels of both stimulus components. For the
      hue judgments, increased background luminance led to greater hue filling-in at
      higher luminances of the interior contour. For the brightness judgments, the
      higher background luminance generated less brightness filling-in at higher
      luminances of the interior contour. The results indicate different effects of the
      inner contour and background on the induction of the brightness and coloration
      percepts of the WCE, suggesting that they are mediated by different mechanisms.

PMID- 29355566
TI  - Spatial proximity modulates the strength of motion opponent suppression elicited
      by locally paired dot displays.
AB  - Locally paired dot stimuli that contain opposing motion signals at roughly the
      same spatial locations (counter-phase stimuli) have been reported to produce
      percepts devoid of global motion. Counter-phase stimuli are also thought to
      elicit a reduced neural response at motion processing brain area MT/V5, an effect
      known as motion opponency. The current study examines the effect of vertical
      counter-phase background motion on behavioral discrimination of horizontal target
      motion. We found that counter-phase backgrounds generally produced lower
      behavioral thresholds than locally unbalanced backgrounds, an effect consistent
      with the idea that counter-phase motion elicits opponency. However, this effect
      was apparent only if the paired dots were close enough in proximity that they
      crossed one another during their movement. Furthermore, we found that counter
      phase stimuli containing within-pair dot crossing elicits similar behavioral
      thresholds to non-motion flicker stimuli. These results provide insight into the
      requirements for activating opponency in the brain and suggest that the brain
      processes counter-phase and flicker stimuli similarly due to opponency.

PMID- 29355567
TI  - Kuwanon G attenuates atherosclerosis by upregulation of LXRalpha-ABCA1/ABCG1 and
      inhibition of NFkappaB activity in macrophages.
AB  - BACKGROUND: Atherosclerosis is characterized by chronic inflammation in vascular
      wall. Previous studies suggest that Kuwanon G (KWG) exerts anti-inflammatory
      activities. However, the effect of KWG on atherosclerosis remains unexplored.
      AIMS: To explore whether KWG affects macrophage foam cell formation in vitro and
      atherogenesis in vivo. METHODS: RAW 264.7 macrophages were stimulated with ox-LDL
      for 24h to induce foam cell formation and treated with KWG. Foam cell formation
      was determined by ORO staining and enzymatic analysis. Pro-inflammatory cytokines
      mRNA levels were tested by Real-time PCR method. Further molecular mechanism was
      investigated using Western blot. In vivo, ApoE-/- mice were fed with high-fat
      diet and intraperitoneally injected with KWG. Atherosclerotic lesion was accessed
      by H&E and ORO staining. Plaque composition was evaluated by immunohistochemistry
      and Sirius Red staining. Serum lipid profile and inflammatory cytokines were
      evaluated by enzymatic method and ELISA. RESULTS: KWG significantly decreased
      intracellular lipid accumulation and inflammatory cytokines mRNA levels in
      macrophages through enhancing LXRalpha-ABCA1/ABCG1 pathway and inhibiting
      NFkappaB activation. Administrated with KWG remarkably reduced the
      atherosclerotic lesion areas and macrophage content in the plaque of high-fat
      diet fed ApoE-/- mice. KWG also reduced hyperlipidemia and serum inflammatory
      cytokines in vivo. CONCLUSION: Taken together, these data highlight that KWG can
      attenuate atherosclerosis through inhibiting foam cell formation and inflammatory
      response.

PMID- 29355568
TI  - Genomic DNA levels of mutant alpha-synuclein correlate with non-motor symptoms in
      an A53T Parkinson's disease mouse model.
AB  - Alpha-synuclein plays a key role in the pathogenesis of Parkinson's disease (PD).
      A robust transgenic mouse model has been generated that overexpresses the mutant
      human A53T alpha-synuclein under the mouse prion protein gene promoter; these
      mice develop age-dependent motor deficits. Recently, compared to wild-type (WT)
      littermates, A53T alpha-synuclein mice were reported to display non-motor symptom
      deficits, e.g., anxiety-like and depressive-like behaviors, odor discrimination
      and detection impairments, and gastrointestinal dysfunction, at 6 months of age
      or older. However, the differences between heterozygous and homozygous mice in
      terms of non-motor symptoms and whether the genomic DNA levels of alpha-synuclein
      correlate with the symptoms have not yet been elucidated. In the present work, we
      used littermate WT and heterozygous and homozygous A53T mice that were
      characterized by a modified genotyping protocol and observed a unilateral decline
      in the dopamine transporter (DAT) distribution from 3 months to 12 months of age
      in homozygous mice. We evaluated non-motor symptoms by measuring colon motility,
      anxiety-like and depressive-like behaviors, and motor coordination. The results
      showed that homozygous A53T mice exhibited earlier abnormal non-motor symptoms
      compared to their heterozygous littermates. The severity of impaired colon
      motility as well as anxiety-like and depressive-like behaviors were correlated
      with the genomic DNA levels of A53T mutant alpha-synuclein. More noticeable,
      motor coordination aberrances were also observed in homozygous A53T mice. This
      study provides direct evidence that the genomic DNA levels of mutant alpha
      synuclein correlate with non-motor symptoms in an A53T mouse model, indicating
      that the genomic DNA levels of mutant alpha-synuclein should be tightly
      manipulated in PD model studies.

PMID- 29355569
TI  - S-oxiracetam ameliorates ischemic stroke induced neuronal apoptosis through up
      regulating alpha7 nAChR and PI3K / Akt / GSK3beta signal pathway in rats.
AB  - Ischemic stroke, the main reason for severe disabilities in the world, is
      associated with a high incidence of sensorimotor and cognitive dysfunction. In
      this study, we use the middle cerebral artery occlusion/reperfusion (MCAO/R)
      model in rats and oxygen glucose deprivation/reoxygenation (OGD/R) model in fetal
      rat primary cortical neurons to investigate whether and how S-oxiracetam (S-ORC)
      protect brain injury from ischemic stroke. The results revealed that S-ORC
      reduced brain infarct size and lessened neurological dysfunction after stroke.
      Further study demonstrated that S-ORC diminished TUNEL positive cells, increased
      cell viability, decreased LDH activity, and inhibited cell apoptotic rate.
      Furthermore, S-ORC inhibited neuronal apoptosis by activating the
      PI3K/Akt/GSK3beta signaling pathway via alpha7 nAChR, which was evidenced by
      alpha7 nAChR siRNA. In conclusion, our findings strongly suggest that S-ORC could
      be used as an effective neuroprotective agent for ischemic stroke due to its
      effect in preventing neuronal apoptosis.

PMID- 29355570
TI  - A novel plasmid, pSAA0430-08, from Streptococcus anginosus subsp. anginosus
      strain 0430-08.
AB  - Mobile genetic elements (MGEs) are the genetic material often involved in the
      interspecies and intraspecies genetic transduction in bacteria. However, little
      is known about MGEs in the Anginosus group of streptococci (AGS), one of the
      streptococcal groups found in the oral cavity of humans. We looked for the
      presence of MGEs in Streptococcus anginosus subsp. anginosus (SAA), a
      representative species belonging to AGS, and found a novel plasmid from SAA
      strain 0430-08. This plasmid was 7038bp and ~31% G/C content which we named
      pSAA0430-08, and examined its genetic structure and characteristics. Open reading
      frame (ORF) prediction revealed that pSAA0430-08 was composed of 10 ORFs
      including a putative plasmid replication protein (ORF1) and a putative toxin
      antitoxin system (ORF9 and ORF10). Between ORF10 and ORF 1, four tandem repeats
      of 22bp each, generally termed as iteron, were also observed. Using variant
      plasmids of pSAA0430-08, we confirmed that both ORF1 and iteron were necessary
      for replication in host cells. Interestingly, the region from ORF4 to ORF7 showed
      homology with a genomic DNA segment of S. gordonii strains. Thus, this plasmid
      may travel between the different species in Streptococci, i.e., S. gordonii and
      S. anginosus.

PMID- 29355571
TI  - Caloric restriction ameliorates acrolein-induced neurotoxicity in rats.
AB  - OBJECTIVE: Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous
      environmental pollutant and oxidative damage induced by acrolein is hypothesized
      to involve in the etiology of Alzheimer's disease (AD). Calorie restriction (CR)
      is the only non-genetic intervention that has consistently been verified to
      retard aging by ameliorating oxidative stress. Therefore, we investigated the
      effects of CR on acrolein-induced neurotoxicity in Sprague-Dawley (SD) rats.
      METHODS: A total of 45 weaned and specific-pathogen-free SD rats (male, weighing
      180-220 g) were gavage-fed with acrolein (2.5 mg/kg/day) and fed ab libitum of 10
      g/day or 7 g/day (representing 30% CR regimen), or gavage-fed with same volume of
      tap water and fed al libitum as vehicle control for 12 weeks. After behavioral
      test conducted by Morris Water Maze, SD rats were sacrificed and brain tissues
      were prepared for histochemical evaluation and Western blotting to detect
      alterations in oxidative stress, BDNF/TrkB pathway and key enzymes involved in
      amyloid precursor protein (APP) metabolism. RESULTS: Treatment with 30% CR in SD
      rats significantly attenuated acrolein-induced cognitive impairment. Oxidative
      damage including deletion of glutathione and superoxide dismutase and sharp rise
      in malondialdehyde were notably improved by 30% CR. Further study suggested that
      30% CR showed protective effects against acrolein by modulating BDNF/TrkB
      signaling pathways. Moreover, 30% CR restored acrolein-induced changes of APP,
      beta-secretase, alpha-secretase and receptor for advanced glycation end products.
      CONCLUSION: These findings suggest that CR may provide a promising approach for
      the treatment of AD, targeting acrolein.

PMID- 29355572
TI  - Revisiting Ureterosigmoidostomy, a Useful Technique of Urinary Diversion in
      Functional Urology.
AB  - Ureterosigmoidostomy has largely been disregarded in recent times but has now
      seen a resurgence of interest because of its potential applicability to newer,
      minimally invasive surgical techniques. The advantages of ureterosigmoidostomy
      over intestinal conduits are urinary continence (obviating the need for stoma and
      external appliances), ease, and rapidity of performance as well as acceptance by
      patients. Ureterosigmoidostomy has been characterized by good continence outcomes
      and it offers good quality of life. Possible complications are anastomosis
      stenosis, coloureteral reflux, electrolyte imbalance, hydronephrosis,
      pyelonephritis, chronic renal failure, colorectal cancer, and others.
      Ureterosigmoidostomy is therefore only advisable for patients ready to accept
      long-term follow-up.

PMID- 29355573
TI  - Spine-bellied sea snake (Hydrophis curtus) venom shows greater skeletal
      myotoxicity compared with cardiac myotoxicity.
AB  - For the first time the impedance-based xCELLigence real-time cell analysis system
      was used to measure the myotoxicity of sea snake venom. With a focus on the spine
      bellied sea snake (Hydrophis curtus), the venom of four sea snake species and
      three terrestrial snake species were compared for myotoxicity against a human
      skeletal muscle cell line (HSkMC). Hydrophis curtus venom was also tested on a
      human cardiac muscle cell line (HCM). Surprisingly, all four sea snake venoms
      tested on HSkMC produced an initial 100-280% rise in xCELLigence cell index that
      peaked within the first two hours before falling. The cell index rise of H.
      curtus venom was correlated with the WST-1 cell proliferation assay, which
      demonstrated an increase in mitochondrial metabolism. The myotoxicity of H.
      curtus was 4.7-8.2 fold less potent than the other sea snakes tested, the
      Australian beaked sea snake (Hydrophis zweifeli), the elegant sea snake
      (Hydrophis elegans) and the olive sea snake (Aipysurus laevis). If our cell-based
      results translate to H. curtus envenomations, this implies that H. curtus would
      be less myotoxic than the other three. Yet the myotoxicity of H. curtus venom to
      cardiac muscle cells was nine times weaker than for skeletal muscle cells,
      providing evidence that the venom has a selective effect on skeletal muscle
      cells. This evidence, combined with the slow-acting nature of the venom, supports
      a digestive role for sea snake myotoxins.

PMID- 29355574
TI  - Efficient construction of xenogeneic genomic libraries by circumventing
      restriction-modification systems that restrict methylated DNA.
AB  - An efficient method to construct xenogeneic genomic libraries with low errors and
      bias by circumventing restriction-modification systems that restrict methylated
      DNA was developed. Un-methylated genomic DNA of Escherichia coli prepared by
      phi29 DNA polymerase was introduced to Corynebacterium glutamicum R after
      ligation with un-methylated vector plasmids.

PMID- 29355575
TI  - Optimized universal protocol for electroporation of both coagulase-positive and 
      negative Staphylococci.
AB  - Electroporation is a common technique necessary for genomic manipulation of
      Staphylococci. However, because this technique has too low efficiency to be
      applied to some Staphylococcal species and strains, especially to coagulase
      negative Staphylococcus (CNS) isolates, basic researches on these clinically
      important Staphylococci are limited. Here we report on the optimization of
      electroporation parameters and conditions as well as on the generation of a
      universal protocol that can be efficiently applicable to both CNS and Coagulase
      positive Staphylococci (CPS). This protocol could generate transformants of
      clinical Staphylococcus epidermidis isolate, with an efficiency of up to 1400
      CFU/MUg of plasmid DNA. Transformants of 12 other clinically important
      Staphylococcal species, including CNS and CPS, were also generated with this
      protocol. To our knowledge, this is the first report on successful
      electroporation in nine these Staphylococcal species.

PMID- 29355576
TI  - Utility of a portable desiccant system for preservation of fecal samples for
      downstream 16S rRNA amplicon sequencing.
AB  - While recent advances in culture-independent sequencing approaches have
      revitalized the field of microbiology, rapid collection and preservation of
      microbial DNA in samples like feces is critical to avoid degradation of target
      DNA via nuclease activity and proliferation of aerotolerant microbes. Common
      laboratory practices to ameliorate such changes rely on prompt freezing of
      samples or dispersion in nuclease-inhibiting reagents. As many of the microbial
      enzymes associated with nuclease activity and bacterial proliferation are
      hydrolases, prompt desiccation of samples offers an attractive alternative to
      freezing and liquid reagents for field collection of samples in remote areas.
      Herein, we evaluated the utility of a portable desiccant chamber with a
      rechargeable cartridge, for preservation of equine fecal samples for downstream
      microbial profiling via 16S rRNA amplicon sequencing. Controls included matched
      samples promptly frozen at -80  degrees C or left at room temperature for an
      equivalent period of time. While samples held at room temperature showed a
      significant reduction in richness and proliferation of several facultative
      anaerobes, desiccated samples showed minimal change from promptly frozen samples,
      with the exception of increased abundance of Acinetobacter spp. in desiccated
      samples relative to frozen samples. The data support the utility of portable
      desiccant chambers for the preservation of microbial field samples intended for
      downstream sequencing approaches.

PMID- 29355577
TI  - High-throughput method for the evaluation of esterase activity in soils.
AB  - We describe a method to quickly evaluate soil esterase activity using p
      nitrophenyl valerate as the substrate. Unwanted coloration of the control samples
      was suppressed by cooling. Esterase activity can be evaluated using arbitrary
      amounts of soil. Sample dispensation was simplified and the number of
      examinations per soil sample reduced.

PMID- 29355578
TI  - Risk factors for hospital norovirus outbreaks: impact of vomiting, genotype, and
      multi-occupancy rooms.
AB  - BACKGROUND: Norovirus is frequently introduced to the hospital and is a frequent
      cause of hospital outbreaks. Recognition of the factors that facilitate or impede
      norovirus transmission is an important step to effectively prevent hospital
      outbreaks. AIM: To investigate risk factors for norovirus outbreaks in hospital
      settings. METHODS: Clinical data, ward setting, and norovirus genotype were
      collected from all 65 norovirus-positive index cases in outbreaks and all 186
      sporadic norovirus cases at 192 wards in southern Sweden during 2010-2012 in a
      nested case-control study. Uni- and multivariate statistical analyses were
      conducted. FINDINGS: Outbreak was independently associated with the number of
      patients sharing a room with the norovirus case (odds ratio (OR): 1.9 per
      additional patient in the room; P < 0.01), vomiting (OR: 2.6; P = 0.04), age >80
      years (OR: 3.2; P < 0.01), comorbidity (OR: 2.3; P = 0.05), and onset of symptoms
      after admission to the ward (OR: 3.5; P < 0.01) in the multivariate analysis.
      Infection with genotype GII.4 was found to be strongly associated with outbreak
      in the univariate analysis (OR: 5.7; P < 0.01). Moreover, associations between
      GII.4 and vomiting (OR: 2.5; P = 0.01) and old age (OR: 4.3: P < 0.01) were
      found. CONCLUSION: This is the first study to investigate clinical, ward and
      genotype risk factors for norovirus hospital outbreaks. Recognition of these
      factors may help direct and prioritize infection control actions based on the
      outbreak risk. The results also suggest that the outbreak association with GII.4
      partly may be explained by an enhanced ability to induce vomiting.

PMID- 29355579
TI  - Interaction of entomopathogenic fungi with the host immune system.
AB  - Entomopathogenic fungi can invade wide range of insect hosts in the natural world
      and have been used as environmentally friendly alternatives to chemical
      insecticides for pest control. Studies of host-pathogen interactions provide
      valuable insights into the coevolutionay arms race between fungal pathogens and
      their hosts. Entomopathogenic fungi have evolved a series of sophisticated
      strategies to counter insect immune defenses. In response to fungal infection,
      insect hosts rely on behavior avoidance, physical barrier and innate immune
      defenses in the fight against invading pathogens. The insect cuticle acts as the
      first physical barrier against pathogens. It is an inhospitable physiological
      environment that contains chemicals (e.g., antimicrobial peptides and reactive
      oxygen species), which inhibit fungal growth. In addition, innate immune
      responses, including cellular immunity and humoral immunity, play critical roles
      in preventing fungal infection. In this review, we outline the current state of
      our knowledge of insect defenses to fungal infection and discuss the strategies
      by which entomopathogenic fungi counter the host immune system. Increased
      knowledge regarding the molecular interactions between entomopathogenic fungi and
      the insect host could provide new strategies for pest management.

PMID- 29355580
TI  - Sitting time is negatively related to microvascular endothelium-dependent
      function in rheumatoid arthritis.
AB  - BACKGROUND: Sedentary behaviour is linked to increased cardiovascular disease
      risk in Rheumatoid Arthritis (RA), but the biological processes underlying this
      relationship are not understood. OBJECTIVES: To investigate the cross-sectional
      associations of habitual sedentary behaviour, with endothelial function in RA.
      METHODS: Sixty-eight RA patients (Mage = 55 +/- 12 years) underwent Laser Doppler
      Imaging with iontophoresis, to assess microvascular endothelium-dependent
      (acetylcholine, ACh) and endothelium-independent (sodium nitroprusside, SNP)
      function. Large-vessel endothelium-dependent and endothelium-independent
      functions were measured via flow-mediated dilation (FMD) and glyceryl trinitrate
      dilation (GTN), respectively. Habitual sedentary behaviour (hours/week sitting)
      was self-reported (International Physical Activity Questionnaire). RESULTS:
      Regressions revealed sitting time significantly negatively predicted
      microvascular endothelium-dependent function (ACh, unstandardizedbeta = -3.25, p
      = .02, 95% CI [-6.07, -.42], R2 = 0.06), but did not associate with other
      endothelial function outcomes (SNP, FMD, GTN). CONCLUSION: Habitual sedentary
      behaviour (sitting time) appears to be adversely linked to microvascular
      endothelium-dependent function among people living with RA.

PMID- 29355581
TI  - A history of sport-related concussion is associated with sustained deficits in
      conflict and error monitoring.
AB  - Previous research has demonstrated long-term deficits in neurocognitive function
      in individuals with a history of sport-related concussion. The purpose of this
      study was to examine the relationship between a history of concussion and
      behavioral and event-related potential (ERP) indices of pre- and post-response
      conflict and error monitoring. A secondary aim was to determine whether years of
      high risk sport participation were related to impairments in these cognitive
      control processes. Forty-seven former athletes (age = 20.8 +/- 2.2 years) with (n
      = 25; 5 females) and without (n = 22; 9 females) a history of concussion
      completed a modified flanker task while behavioral performance, N2, error-related
      negativity (ERN), and error positivity (Pe) components were assessed. An increase
      in post-response error-related (ERN) brain activity and a nonsignificant trend of
      increased pre-response conflict (N2) was observed in individuals with a prior
      sport-related concussion relative to non-concussed controls; however, no
      behavioral performance differences were found between groups. No significant
      associations were found between ERP and behavioral measures and the number of
      years of high-risk sport participation; however, time since last head injury was
      associated with shorter N2 latency. Together, these findings suggest a persistent
      impairment in cognitive control and error-related processing in individuals with
      a history of concussion. These findings are interpreted within the framework of
      the compensatory error-monitoring hypothesis.

PMID- 29355583
TI  - Involvement of cystatin C in immunity and apoptosis.
AB  - As an abundantly expressed cysteine protease inhibitor widely distributed in the
      organisms, cystatin C is involved in various physiological processes. Due to its
      relatively small molecular weight and easy detection, cystatin C is commonly used
      as a measure for glomerular filtration rate. In pathological conditions, however,
      growing evidences suggest that cystatin C is associated with various immune
      responses against either exogenous or endogenous antigens, which ultimately
      result in inflammatory autoimmune diseases or tumor development if not properly
      controlled. Thus the fluctuation of cystatin C levels might have more clinical
      implications than a reflection of kidney functions. Here, we summarize the latest
      development of studies on the pathophysiological functions of cystatin C, with
      focus on its immune regulatory roles at both cellular and molecular levels
      including antigen presentation, secretion of cytokines, synthesis of nitric
      oxide, as well as apoptosis. Finally, we discuss the clinical implications and
      therapeutic potentials of what this predominantly expressed protease inhibitor
      can bring to us.

PMID- 29355582
TI  - Targeting Heat Shock Protein 70 as an antiviral strategy against grass carp
      reovirus infection.
AB  - Grass carp (Ctenopharyngodon idella) hemorrhagic disease, caused by grass carp
      reovirus (GCRV), has been a serious problem in grass carp aquaculture for several
      decades. Characterization of the primary host factors associated with host-virus
      interaction is critical for understanding how a virus infects its host cell and
      these host factors can be antiviral targets. This study aimed to screen host
      factors that interacted with GCRV in the C. idella kidney (CIK) cells and used
      them as antiviral targets. Twelve proteins were identified by virus overlay
      protein binding assay and LC-MS-MS. Among these twelve proteins, Heat Shock
      Protein 70 (HSP70) was outstanding. Results of flow cytometry and
      immunofluorescence assay indicated that HSP70 was on the cell membrane. HSP70 was
      expressed at low levels preceding GCRV infection, but its expression was induced
      upon GCRV infection. Inhibition of HSP70's function by inhibitors (VER155008 and
      pifithrin-MU) maintained HSP70 on the cell surface in infected cells, however
      GCRV quantity was decreased in the CIK cells (compared with the control group,
      the maximum inhibition rate of the treatment group was close to 85%), suggesting
      that fully functional HSP70 was required for GCRV infection. Moreover, GCRV
      showed a dose dependent reduction by inhibiting the entry stage of the viral life
      cycle following treated with VER155008 and pifithrin-MU. VER + PIF (1:1) were
      used at 15 MUM and the expression of GCRV-VP6 downregulated nearly to 90%, which
      revealed that HSP70 played an important role in GCRV entering into CIK cells.
      This work speculated that HSP70 might be a host factor in the process of GCRV
      infecting CIK cells, therefore, it might be a potential antiviral target for GCRV
      infection.

PMID- 29355584
TI  - Dietary patterns associated with overweight among Brazilian adolescents.
AB  - The present study aims to identify the dietary patterns of adolescents and
      associate these patterns with overweight. We analyzed food-consumption data from
      6784 adolescents in the age group 10-18 years old collected in the Household
      Budget Survey 2008-2009. Dietary patterns were assessed through exploratory
      factor analysis. Logistic regression models were used in order to associate
      dietary patterns with overweight. Four dietary patterns were recorded:
      Traditional Brazilian Pattern, Snacks Pattern, Fast Food Pattern, and the Milk,
      Fruit and Cereal Breakfast Pattern. Results were adjusted according to the
      sociodemographic variables and showed that the higher the adherence to Snacks
      (OR: 1.50 fifth quintile vs first (95% CI: 1.13, 1.99) p linear trend <0.001) and
      Fast Food patterns (OR: 1.55 fifth quintile vs first (95% CI = 1.12, 2.12) p
      linear trend <0.001), the higher the chances of becoming overweight. These data
      indicate that the local public health and nutrition policies focused on
      adolescents should be more attentive to the eating habits of this population in
      Brazil, since the current research related regular poor nutritional quality
      dietary patterns to increased overweight among adolescents. In addition,
      understanding adolescents' eating habits according to their dietary patterns may
      guide the development of healthy dietary recommendations based on the combination
      between food and food groups, rather than only on nutrients or nutritional
      adequacy.

PMID- 29355585
TI  - High degree of correlation between Ebola virus BSL-4 neutralization assays and
      pseudotyped VSV BSL-2 fluorescence reduction neutralization test.
AB  - Ebola virus (EBOV), classified as a category A agent by the CDC and NIH, requires
      BSL-4 containment and induces high morbidity and mortality in humans. The 2013
      2015 epidemic in West Africa underscored the urgent need to develop vaccines and
      therapeutics to prevent and treat EBOV disease. Neutralization assays are needed
      to evaluate the efficacy of EBOV vaccines and antibody therapies. Pseudotyped
      viruses based on nonpathogenic or attenuated vectors reduce the risks involved in
      the evaluation of neutralizing antibodies against highly pathogenic viruses.
      Selectable markers, fluorescent proteins, and luciferase have been introduced
      into pseudotyped viruses for detection and quantitation purposes. The current
      study describes the development of a BSL-2 fluorescence reduction neutralization
      test (FRNT) using a recombinant vesicular stomatitis virus (VSV) in which the VSV
      G envelope gene was replaced with the EBOV glycoprotein (GP) and green
      fluorescent protein (GFP) genes (rVSV-EBOVgp-GFP). Cells infected with rVSV
      EBOVgp-GFP express GFP. Anti-GP neutralizing monoclonal and polyclonal antibodies
      blocked rVSV-EBOVgp-GFP infection preventing or reducing GFP fluorescence. The
      high degree of correlation between the EBOV BSL-2 FRNT and the BSL-4 plaque
      reduction neutralization test (PRNT), the accepted standard of EBOV
      neutralization tests, supports the use of the EBOV BSL-2 FRNT to evaluate
      neutralizing antibodies in clinical trials.

PMID- 29355586
TI  - Ras-Raf-MAPK signaling promotes nuclear localization of FOXA transcription factor
      SGF1 via Ser91 phosphorylation.
AB  - Ras-Raf-MAPK signaling promotes cell proliferation and cell survival. We
      previously reported that Ras1CA overexpression, specifically in the posterior
      silk glands (PSGs) of the silkworm Bombyx mori, increased fibroin synthesis and
      cell size, resulting in improved silk yields. In this study, we compared the
      iTRAQ-based phosphoproteomic profiles of PSGs from wild-type and Ras1CA
      overexpressing silkworms. Silk gland factor 1 (SGF1), a FOXA transcription factor
      that plays a critical role in activating fibroin gene expression, was identified
      as a phosphoprotein harboring Ser91 as a potential MAPK phosphorylation site.
      Ser91 phosphorylation of SGF1 was enhanced by Ras1CA overexpression, and this
      finding was verified by selected reaction monitoring. Consistently, MAPK activity
      is well correlated with Ser91 phosphorylation of SGF1 and its nuclear
      localization in PSG cells during silkworm development. Ras1CA overexpression and
      treatment with inhibitors of Ras signaling promoted or inhibited SGF1 nuclear
      localization, respectively; mutation of Ser91 to Ala91 eliminated SGF1 nuclear
      localization. Moreover, MAPK binds to SGF1 and directly phosphorylates Ser91,
      demonstrating Ser91 as a MAPK phosphorylation site in SGF1. In conclusion, Ras
      Raf-MAPK signaling promotes SGF1 nuclear localization for transactivation via
      Ser91 phosphorylation in silkworms, showing that FOXA transcription factors are
      regulated via MAPK phosphorylation in animals.

PMID- 29355588
TI  - Resting-state functional connectivity of neurotransmitter producing sites in
      female patients with borderline personality disorder.
AB  - Impulsive behavior, difficulties in controlling anger and suicidal behavior are
      typical patterns of affective/behavioral dysregulation in patients with
      borderline personality disorder (BPD). Previous functional MRI studies in the
      resting state condition demonstrated altered functional connectivity (FC) between
      the anterior cingulate cortex (ACC) and the frontoparietal executive control
      network (ECN), which was significantly associated with impulsivity in BPD.
      Impulsivity is often defined as a function of inhibitory control, strongly
      relying on the proper functioning of the fronto-cingulo-striatal network.
      Noradrenergic, dopaminergic and serotonergic neurotransmitter systems are assumed
      to be involved in different forms of impulsive behavior and inhibitory control.
      In our previous study, we investigated the FC of the main monoamine-producing
      nuclei within the midbrain and brainstem, which were functionally integrated in
      specific resting-state networks. In the present study we investigated the resting
      state FC of midbrain/brainstem nuclei in 33 unmedicated female patients with BPD
      and 33 matched healthy controls. We further related altered functional
      connectivity of these nuclei to the patient's degree of impulsivity. The main
      finding was that BPD patients showed stronger FC from the noradrenergic locus
      coeruleus (LC) to the ACC. Functional connectivity between the LC and ACC was
      positively associated with the degree of motor impulsivity in the total group.
      Controlling for aggression, a stronger FC was also found between serotonergic
      nucleus centralis superior (NCS) and the frontopolar cortex (FPC) in patients
      compared to controls. Furthermore, patients showed a weaker "anti-correlation"
      from the substantia nigra (SNc) to the left dorsolateral prefrontal cortex
      (DLPFC). The observed enhanced LC-ACC FC in BPD and its association with the
      motor impulsivity might be indicative of a noradrenergic dysfunction in the
      neural inhibitory control network, whereas the significant relationship between
      NCS-FPC FC and aggression points toward serotonergic contribution to prefrontal
      control of aggressive reactions.

PMID- 29355589
TI  - The AGP-PPARgamma axis promotes oxidative stress and diabetic endothelial cell
      dysfunction.
AB  - Alkyl-glycerophosphate (AGP) accumulates in atherogenic oxidized-LDL and human
      atherosclerotic plaques and is a potent agonist of peroxisome-proliferator
      activated receptor-gamma (PPARgamma). Recent studies suggest a potential
      regulatory role for PPARgamma in endothelial nitric oxide synthase (eNOS)
      expression/activation and nitrogen oxide (NO) generation in the vascular
      endothelium. Importantly, eNOS-induced NO and advanced glycation end-products
      (AGEs) are involved in blood-vessel damage, and diabetic patients exhibit high
      serum NO and AGE levels; however, the effect of AGP on NO- and AGE-mediated
      endothelium dysfunction remains unknown. Investigation of the AGP-specific
      effects on NO- and AGE-mediated dysfunction and the underlying molecular
      mechanisms revealed that AGP upregulated eNOS expression and NO production, and
      that eNOS silencing and PPARgamma antagonism inhibited AGP-mediated eNOS
      upregulation and NO production. Moreover, AGP-PPARgamma-axis-mediated NO
      production promoted the generation of reactive oxygen species and AGE formation.
      These results suggested that AGP plays a significant role in the
      initiation/progression of diabetes-related atherosclerosis through PPARgamma
      activation.

PMID- 29355590
TI  - Targeting TGF-beta signaling for the treatment of fibrosis.
AB  - Transforming growth factor-beta (TGF-beta) is widely recognized as a core pathway
      of fibrosis. Inhibition of TGF-beta signaling may thus offer potential for
      antifibrotic therapies. Long-term inhibition of TGF-beta signaling at the level
      of its isoforms and receptors can be associated with unacceptable adverse
      effects. However, TGF-beta regulates a myriad of intracellular signaling cascades
      to transmit its profibrotic effects and several of those pathways offer potential
      for pharmacologic intervention. Moreover, the multiple interactions of TGF-beta
      with other profibrotic pathways also yielded candidates for therapeutic
      intervention. In this review, we discuss selected targets within the TGF-beta
      pathway with high translational potential.

PMID- 29355591
TI  - Chaperoning the guardian of the genome. The two-faced role of molecular
      chaperones in p53 tumor suppressor action.
AB  - Organized networks of heat shock proteins, which possess molecular chaperone
      activity, protect cells from abrupt environmental changes. Additionally,
      molecular chaperones are essential during stress-free periods, where they
      moderate housekeeping functions. During tumorigenesis, these chaperone networks
      are extensively remodeled in such a way that they are advantageous to the
      transforming cell. Molecular chaperones by buffering critical elements of
      signaling pathways empower tumor evolution leading to chemoresistance of cancer
      cells. Controversially, the same molecular chaperones, which are indispensable
      for p53 in reaching its tumor suppressor potential, are beneficial in adopting an
      oncogenic gain of function phenotype when TP53 is mutated. On the molecular
      level, heat shock proteins by unwinding the mutant p53 protein expose aggregation
      prone sites leading to the sequestration of other tumor suppressor proteins
      causing inhibition of apoptosis and chemoresistance. Therefore, within this
      review therapeutic approaches combining classical immuno- and/or chemotherapy
      with specific inhibition of selected molecular chaperones shall be discussed.

PMID- 29355592
TI  - Down-regulation of Inwardly Rectifying K+ Currents in Astrocytes Derived from
      Patients with Monge's Disease.
AB  - Chronic mountain sickness (CMS) or Monge's disease is a disease in highlanders.
      These patients have a variety of neurologic symptoms such as migraine, mental
      fatigue, confusion, dizziness, loss of appetite, memory loss and neuronal
      degeneration. The cellular and molecular mechanisms underlying CMS neuropathology
      is not understood. In the previous study, we demonstrated that neurons derived
      from CMS patients' fibroblasts have a decreased expression and altered gating
      properties of voltage-gated sodium channel. In this study, we further
      characterize the electrophysiological properties of iPSC-derived astrocytes from
      CMS patients. We found that the current densities of the inwardly rectifying
      potassium (Kir) channels in CMS astrocytes (-5.7 +/- 2.2 pA/pF at -140 mV) were
      significantly decreased as compared to non-CMS (-28.4 +/- 3.4 pA/pF at -140 mV)
      and sea level subjects (-28.3 +/- 5.3 pA/pF at -140 mV). We further demonstrated
      that the reduced Kir current densities in CMS astrocytes were caused by their
      decreased protein expression of Kir4.1 and Kir2.3 channels, while single channel
      properties (i.e., Po, conductance) of Kir channel in CMS astrocytes were not
      altered. In addition, we found no significant differences of outward potassium
      currents between CMS and non-CMS astrocytes. As compared to non-CMS and sea level
      subjects, the K+ uptake ability in CMS astrocytes was significantly decreased.
      Taken together, our results suggest that down-regulation of Kir channels and the
      resulting decreased K+ uptake ability in astrocytes could be one of the major
      molecular mechanisms underlying the neurologic manifestations in CMS patients.

PMID- 29355593
TI  - An approach to testing undiluted e-cigarette aerosol in vitro using 3D
      reconstituted human airway epithelium.
AB  - The data presented here show that to provide an estimate of the relative
      cytotoxicity and therefore potency of e-cigarettes, undiluted aerosol techniques
      can be used. With the emergence of electronic nicotine delivery systems, fit-for
      purpose in vitro screening methods are required. Reconstituted 3D human airway
      epithelium, was exposed to undiluted aerosols at the air-liquid interface, using
      a Vitrocell VC 10. TEER, cilia beat frequency and cytotoxic responses were
      assessed. Using two smoking regimes (ISO and HCI) a 3R4F reference cigarette,
      produced IC50s of 5.2 and 2.1 min, 1458 ng/mL and 1640 ng/mL nicotine
      respectively. Using an open tank e-cigarette device, a full cytotoxicity dose
      response curve was obtained giving an IC50 of 30 min with corresponding nicotine
      of 10,957 ng/mL, 6-14 times less cytotoxic than cigarette smoke. A commonly used
      e-liquid flavourant cinnamaldehyde and known skin sensitizer was added to the
      standard e-liquid formulation and used as an aerosolised positive control, at
      0.1, 0.025, 0.01 and 0%, demonstrating a full dose response. The delivery of
      undiluted aerosols in vitro has resulted in increased method sensitivity,
      throughput and quantitative e-cigarette comparisons. A positive control aerosol
      generated from a 'safe' e-liquid benchmark can inform risk assessments on
      supportable levels of flavour ingredients.

PMID- 29355594
TI  - In vitro characterization of ritonavir formulations and correlation to in vivo
      performance in dogs.
AB  - Ritonavir (RTV) is a weakly basic drug with a pH-dependent solubility. In vitro
      characterization of dissolution and supersaturation behaviors of three PEG-8000
      based amorphous solid dispersions (ASD) and a physical blend (PB) with
      crystalline drug were performed in the biomimetic media (e.g., FaSSGF, FaSSIF,
      FaSSIF-V2). A two-stage dissolution test and a biphasic dissolution-partition
      test at the small scale (referred as to biphasic test) were employed with
      intention to examine the in vitro and in vivo relationship (IVIVR) with
      retrospective PK data in dog model. The two-stage dissolution test revealed a
      high degree of supersaturation of RTV from these ASDs accompanied by the
      occurrence of liquid-liquid phase separation (LLPS) in the biomimetic media. A
      rapid decrease of apparent RTV concentrations of these ASDs was associated with
      significant precipitation upon the pH shift of the dissolution medium, revealing
      the important role of "the gastric stage". In comparison, the biphasic test
      revealed a lower degree of supersaturation of RTV that is attributed to removal
      of RTV through partition into octanol, acting as "the absorption compartment".
      These two dissolution tests provide characterization of the supersaturation state
      with a complex, dynamic interplay among dissolution, precipitation and partition
      processes. Results of both in vitro dissolution tests are in good agreement with
      in vivo results in dogs. In addition, three commercial generic RTV drug products
      were examined by the biphasic test. Agreement was also obtained between the RTV
      concentrations in octanol at 3 h from these generic drug products and their
      corresponding relative bioavailability in dogs.

PMID- 29355595
TI  - Curcumin drug delivery by vanillin-chitosan coated with calcium ferrite hybrid
      nanoparticles as carrier.
AB  - The aim of the present investigation is the development, optimization and
      characterization of curcumin-loaded hybrid nanoparticles of vanillin-chitosan
      coated with super paramagnetic calcium ferrite. The functionally modified
      vanillin-chitosan was prepared by the Schiff base reaction to enhance the
      hydrophobic drug encapsulation efficiency. Calcium ferrite (CFNP) nano particles
      were added to the vanillin modified chitosan to improve the biocompatibility. The
      vanillin-chitosan-CFNP, hybrid nanoparticle carrier was obtained by ionic
      gelation method. Characterizations of the hybrid materials were performed by XRD,
      FTIR, 1H NMR, TGA, AFM and SEM techniques to ensure the modifications on the
      chitosan material. Taguchi method was applied to optimize the drug (curcumin)
      encapsulation efficiency by varying the drug to chitosan-vanillin, CFNP to
      chitosan-vanillin and TPP (sodium tripolyphospate) to chitosan-vanillin ratios.
      The maximum encapsulation efficiency was obtained as 98.3% under the conditions
      of 0.1, 0.75 and 1.0 for the drug to chitosan-vanillin, CFNP to chitosan-vanillin
      and TPP to chitosan-vanillin ratios, respectively. The curcumin release was
      performed at various pH, initial drug loading concentrations and magnetic fields.
      The drug release mechanism was predicted by fitting the experimental kinetic data
      with various drug release models. The drug release profiles showed the best fit
      with Higuchi model under the most of conditions. The drug release mechanism
      followed both non-Fickian diffusion and case II transport mechanism for chitosan,
      however the non-Fickian diffusion mechanism was followed for the vanillin
      modified chitosan. The biocompatibility of the hybrid material was tested using
      L929 fibroblast cells. The cytotoxicity test was performed against MCF-7 breast
      cancer cell line to check the anticancer property of the hybrid nano carrier with
      the curcumin drug.

PMID- 29355596
TI  - Ubiquitin-activating enzyme E1 inhibitor PYR-41 retards sperm enlargement after
      fusion to the egg.
AB  - The ubiquitin-proteasome system, which is initiated by a single ubiquitin
      activating enzyme E1 (UBE1), is involved in male reproduction via spermatogenesis
      and function in mammals. Here we explored the influence of UBE1-specific
      inhibitor, 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic
      acid ethyl ester (pyrazone-41 or PYR-41) in female reproduction. UBE-1 was
      detected by immunoblotting and immunocytochemistry in mouse eggs and was
      localized mainly under the egg plasma membrane. PYR-41 pretreatment suppresses
      the development of eggs into two-cell embryos. Specifically, pretreatment
      retarded sperm enlargement and meiotic chromosomal division after sperm-egg
      fusion. PYR-41 pretreatment disturbed beta-catenin, a well-known target protein
      for ubiquitination, localization under the egg plasma membrane and on spindle
      microtubules in wild-type eggs. Otherwise, PYR-41 treatment had no effect on the
      two-cell development of eggs lacking beta-catenin. Our results raise the
      possibility that inhibition of the ubiquitin-proteasome system suppresses sperm
      enlargement through impaired beta-catenin-mediated mechanism.

PMID- 29355597
TI  - Elucidating the gene regulatory networks modulating cancer stem cells and non
      stem cancer cells in high grade serous ovarian cancer.
AB  - The origin and pathogenesis of epithelial ovarian cancer have perplexed
      investigators for decades. The most prevalent type of it is the high-grade serous
      ovarian carcinoma (HGSOv) which is a highly aggressive disease with high relapse
      rates and insurgence of chemo-resistance at later stages of treatment. These are
      driven by a rare population of stem cell like cancer cells called cancer stem
      cells (CSCs). We have taken up a systems approach to find out the common gene
      interaction paths between non-CSC tumor cells (CCs) and CSCs in HGSOv. Detailed
      investigation reveals a set of 17 Transcription Factors (named as pivot-TFs)
      which can govern changes in the mode of gene regulation along these paths.
      Overall, this work highlights a divergent road map of functional information
      relayed by these common key players in the two cell states, which might aid
      towards designing novel therapeutic measures to target the CSCs for ovarian
      cancer therapy.

PMID- 29355587
TI  - The role of the orbitofrontal cortex in alcohol use, abuse, and dependence.
AB  - One of the major functions of the orbitofrontal cortex (OFC) is to promote
      flexible motivated behavior. It is no surprise, therefore, that recent work has
      demonstrated a prominent impact of chronic drug use on the OFC and a potential
      role for OFC disruption in drug abuse and addiction. Among drugs of abuse, the
      use of alcohol is particularly salient with respect to OFC function. Although a
      number of studies in humans have implicated OFC dysregulation in alcohol use
      disorders, animal models investigating the association between OFC and alcohol
      use are only beginning to be developed, and there is still a great deal to be
      revealed. The goal of this review is to consider what is currently known
      regarding the role of the OFC in alcohol use and dependence. I will first provide
      a brief, general overview of current views of OFC function and its contributions
      to drug seeking and addiction. I will then discuss research to date related to
      the OFC and alcohol use, both in human clinical populations and in non-human
      models. Finally I will consider issues and strategies to guide future study that
      may identify this brain region as a key player in the transition from moderated
      to problematic alcohol use and dependence.

PMID- 29355598
TI  - Biological activities of (-)-epicatechin and (-)-epicatechin-containing foods:
      Focus on cardiovascular and neuropsychological health.
AB  - Recent studies have suggested that certain (-)-epicatechin-containing foods have
      a blood pressure-lowering capacity. The mechanisms underlying (-)-epicatechin
      action may help prevent oxidative damage and endothelial dysfunction, which have
      both been associated with hypertension and certain brain disorders. Moreover, (-)
      epicatechin has been shown to modify metabolic profile, blood's rheological
      properties, and to cross the blood-brain barrier. Thus, (-)-epicatechin causes
      multiple actions that may provide unique synergy beneficial for cardiovascular
      and neuropsychological health. This review summarises the current knowledge on
      the biological actions of (-)-epicatechin, related to cardiovascular and brain
      functions, which may play a remarkable role in human health and longevity.

PMID- 29355599
TI  - Stable isotope compounds - production, detection, and application.
AB  - Stable isotopes are used in wide fields of application from natural tracers in
      biology, geology and archeology through studies of metabolic fluxes to their
      application as tracers in quantitative proteomics and structural biology. We
      review the use of stable isotopes of biogenic elements (H, C, N, O, S, Mg, Se)
      with the emphasis on hydrogen and its heavy isotope deuterium. We will discuss
      the limitations of enriching various compounds in stable isotopes when produced
      in living organisms. Finally, we overview methods for measuring stable isotopes,
      focusing on methods for detection in single cells in situ and their exploitation
      in modern biotechnologies.

PMID- 29355600
TI  - Mechanisms of canalicular transporter endocytosis in the cholestatic rat liver.
AB  - Impaired canalicular secretion due to increased endocytosis and intracellular
      retention of canalicular transporters such as BSEP and MRP2 is a main, common
      pathomechanism of cholestasis. Nevertheless, the mechanisms governing this
      process are unknown. We characterized this process in estradiol 17 beta-d
      glucuronide (E17G)-induced cholestasis, an experimental model which partially
      mimics pregnancy-induced cholestasis. Inhibitors of clathrin-mediated endocytosis
      (CME) such as monodansylcadaverine (MDC) or K+ depletion, but not the caveolin
      mediated endocytosis inhibitors filipin and genistein, prevented E17G-induced
      endocytosis of BSEP and MRP2, and the associated impairment of activity of these
      transporters in isolated rat hepatocyte couplets (IRHC). Immunofluorescence and
      confocal microscopy studies showed that, in E17G-treated IRHC, there was a
      significant increase in the colocalization of MRP2 with clathrin, AP2, and Rab5,
      three essential members of the CME machinery. Knockdown of AP2 by siRNA in
      sandwich-cultured rat hepatocytes completely prevented E17G-induced endocytosis
      of BSEP and MRP2. MDC significantly prevented this endocytosis, and the
      impairment of bile flow and biliary secretion of BSEP and MRP2 substrates, in
      isolated and perfused livers. BSEP and MRP2, which were mostly present in raft
      (caveolin-enriched) microdomains in control rats, were largely found in non-raft
      (clathrin-enriched) microdomains in livers from E17G-treated animals, from where
      they can be readily recruited for CME. In conclusion, our findings show that CME
      is the mechanism responsible for the internalization of the canalicular
      transporters BSEP and MRP2 in E17G-induced cholestasis. The shift of these
      transporters from raft to non-raft microdomains could be a prerequisite for the
      transporters to be endocytosed under cholestatic conditions.

PMID- 29355601
TI  - Nickel ions bind to HSP90beta and enhance HIF-1alpha-mediated IL-8 expression.
AB  - Nickel ions (Ni2+) eluted from biomedical devices cause inflammation and Ni
      allergy. Although Ni2+ and Co2+ elicit common effects, Ni2+ induces a generally
      stronger inflammatory reaction. However, the molecular mechanism by which Ni2+
      and Co2+ induce such different responses remains to be elucidated. In the present
      study, we compared the effects of Ni2+ and Co2+ on the expression of interleukin
      (IL)-8 in human monocyte THP-1 cells. We report that NiCl2 but not CoCl2 induced
      the expression of IL-8; in contrast, CoCl2 elicited a higher expression of
      hypoxia-inducible factor-1alpha (HIF-1alpha). The NiCl2-induced expression of IL
      8 in late phase was blocked by a HIF-1alpha inhibitor, PX-478, indicating that
      NiCl2 targets additional factors responsible for activating HIF-1alpha. To
      identify such targets, proteins that bound preferentially to Ni-NTA beads were
      analyzed by LC/MS/MS. The analysis yielded heat shock protein 90beta (HSP90beta)
      as a possible candidate. Furthermore, Ni2+ reduced the interaction of HSP90beta
      with HIF-1alpha, and instead promoted the interaction between HIF-1alpha and HIF
      1beta, as well as the nuclear localization of HIF-1alpha. Using various deletion
      variants, we showed that Ni2+ could bind to the linker domain on HSP90beta. These
      results suggest that HSP90beta plays important roles in Ni2+-induced production
      of IL-8 and could be a potential target for the regulation of Ni2+-induced
      inflammation.

PMID- 29355603
TI  - Targeting PERK signaling with the small molecule GSK2606414 prevents
      neurodegeneration in a model of Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder,
      leading to the progressive decline of motor control due to the loss of
      dopaminergic neurons in the substantia nigra pars compacta (SNpc). Accumulating
      evidence suggest that altered proteostasis is a salient feature of PD,
      highlighting perturbations to the endoplasmic reticulum (ER), the main
      compartment involved in protein folding and secretion. PERK is a central ER
      stress sensor that enforces adaptive programs to recover homeostasis through a
      block of protein translation and the induction of the transcription factor ATF4.
      In addition, chronic PERK signaling results in apoptosis induction and neuronal
      dysfunction due to the repression in the translation of synaptic proteins. Here
      we confirmed the activation of PERK signaling in postmortem brain tissue derived
      from PD patients and three different rodent models of the disease.
      Pharmacological targeting of PERK by the oral administration of GSK2606414
      demonstrated efficient inhibition of the pathway in the SNpc after experimental
      ER stress stimulation. GSK2606414 protected nigral-dopaminergic neurons against a
      PD-inducing neurotoxin, improving motor performance. The neuroprotective effects
      of PERK inhibition were accompanied by an increase in dopamine levels and the
      expression of synaptic proteins. However, GSK2606414 treated animals developed
      secondary effects possibly related to pancreatic toxicity. This study suggests
      that strategies to attenuate ER stress levels may be effective to reduce
      neurodegeneration in PD.

PMID- 29355602
TI  - Natural product andrographolide alleviated APAP-induced liver fibrosis by
      activating Nrf2 antioxidant pathway.
AB  - As a well-known analgesic drug, acetaminophen (APAP) is commonly used to relieve
      pain for patients with chronic painful diseases. Our previous study has shown
      that long-term ingestion of APAP caused liver fibrosis in mice. This study
      further investigated the critical role of nuclear factor erythroid 2-related
      factor 2 (Nrf2) in regulating APAP-induced liver fibrosis in mice and the anti
      fibrotic effect of natural compound andrographolide (Andro). Our results showed
      that hepatic collagen deposition and hepatic stellate cells (HSCs) activation
      induced by APAP were more serious in Nrf2 knock-out mice than in normal wild-type
      mice. Andro reduced HSCs activation in vitro, and also decreased hepatic collagen
      deposition and HSCs activation induced by APAP in mice. Andro alleviated liver
      oxidative stress injury induced by APAP in mice and reduced cellular formation of
      reactive oxygen species (ROS) in HSCs. Andro enhanced Nrf2 nuclear translocation
      and increased the expression of Nrf2 downstream antioxidant genes both in vitro
      and in vivo. Furthermore, the Andro-provided protection against APAP-induced
      liver fibrosis was diminished in Nrf2 knock-out mice. In summary, Nrf2 is
      critically involved in preventing liver fibrosis induced by long-term
      administration of APAP in mice, and Andro alleviates APAP-induced liver fibrosis
      by attenuating liver oxidative stress injury via inducing Nrf2 activation. This
      study points out the potential application of Andro in the treatment of liver
      fibrosis in clinic.

PMID- 29355604
TI  - In-depth phylodynamics, evolutionary analysis and in silico predictions of
      universal epitopes of Influenza A subtypes and Influenza B viruses.
AB  - This study applied High-Performance Computing to explore the high-resolution
      phylodynamics and the evolutionary dynamics of Influenza viruses (IVs) A and B
      and their subtypes in-depth to identify peptide-based candidates for broad
      spectrum vaccine targets. For this purpose, we collected all the available
      Hemagglutinin (HA) and Neuraminidase (NA) nucleotide and amino acid sequences
      (more than 100,000) of IVs isolated from all the reservoirs and intermediate
      hosts species, from all geographic ranges and from different isolation sources,
      covering a period of almost one century of sampling years. We highlight that
      despite the constant changes in Influenza evolutionary dynamics over time, which
      are responsible for the generation of novel strains, our study identified the
      presence of highly conserved peptides distributed in all the HA and NA found in
      H1-H18 and N1-N11 IAV subtypes and IBVs. Additionally, predictions through
      computational methods showed that these peptides could have a strong affinity to
      bind to HLA-A*02:01/HLA-DRB1*01:01 major histocompatibility complex (MHC) class I
      and II molecules, therefore acting as a double ligand. Moreover, epitope
      prediction in antigens from pathogens responsible for secondary bacterial
      infection was also studied. These findings show that the regions mapped here may
      potentially be explored as universal epitope-based candidates to develop
      therapies leading to a broader response against the infection induced by all
      circulating IAVs, IBVs and Influenza-associated bacterial infections.

PMID- 29355606
TI  - Enteric alpha-defensins on the verge of intestinal immune tolerance and
      inflammation.
AB  - The gut is the biggest immune organ in the body that encloses commensal
      microbiota which aids in food digestion. Paneth cells, positioned at the
      frontline of host-microbiota interphase, can modulate the composition of
      microbiota. Paneth cells achieve this via the delivery of microbicidal
      substances, among which enteric alpha-defensins play the primary role. If
      microbiota is dysregulated, it can impact the function of the local mucosal
      immune system. Importantly, this system is also exposed to an enormous number of
      antigens which are derived from the gut-resident microbiota and processed food,
      and may potentially trigger undesirable local inflammatory responses. To
      understand the intricate regulations and liaisons between Paneth cells,
      microbiota and the immune system in this intestinal-specific setting, one must
      consider their mode of interaction in a wider context of regulatory processes
      which impose immune tolerance not only to self, but also to microbiota and food
      derived antigens. These include, but are not limited to, tolerogenic mechanisms
      of central tolerance in the thymus and peripheral tolerance in the secondary
      lymphoid organs, and the intestine itself. Defects in these processes can
      compromise homeostasis in the intestinal mucosal immunity. In this review, which
      is focused on tolerance to intestinal antigens and its relevance for the
      pathogenesis of gut immune diseases, we provide an outline of such multilayered
      immune control mechanisms and highlight functional links that underpin their
      cooperative nature.

PMID- 29355605
TI  - Sharing mutants and experimental information prepublication using FgMutantDb
      (https://scabusa.org/FgMutantDb).
AB  - There is no comprehensive storage for generated mutants of Fusarium graminearum
      or data associated with these mutants. Instead, researchers relied on several
      independent and non-integrated databases. FgMutantDb was designed as a simple
      spreadsheet that is accessible globally on the web that will function as a
      centralized source of information on F. graminearum mutants. FgMutantDb aids in
      the maintenance and sharing of mutants within a research community. It will serve
      also as a platform for disseminating prepublication results as well as negative
      results that often go unreported. Additionally, the highly curated information on
      mutants in FgMutantDb will be shared with other databases (FungiDB, Ensembl,
      PhytoPath, and PHI-base) through updating reports. Here we describe the creation
      and potential usefulness of FgMutantDb to the F. graminearum research community,
      and provide a tutorial on its use. This type of database could be easily emulated
      for other fungal species.

PMID- 29355607
TI  - Interplay between co-divergence and cross-species transmission in the
      evolutionary history of bat coronaviruses.
AB  - Coronaviruses (CoVs) have been documented in almost every species of bat sampled.
      Bat CoVs exhibit both extensive genetic diversity and a broad geographic range,
      indicative of a long-standing host association. Despite this, the respective
      roles of long-term virus-host co-divergence and cross-species transmission (host
      jumping) in the evolution of bat coronaviruses are unclear. Using a phylogenetic
      approach we provide evidence that CoV diversity in bats is shaped by both species
      richness and their geographical distribution, and that CoVs exhibit clustering at
      the level of bat genera, with these genus-specific clusters largely associated
      with distinct CoV species. Co-phylogenetic analyses revealed that cross-species
      transmission has been more common than co-divergence across coronavirus evolution
      as a whole, and that cross-species transmission events were more likely between
      sympatric bat hosts. Notably, however, an analysis of the CoV RNA polymerase
      phylogeny suggested that many such host-jumps likely resulted in short-term spill
      over infections, with little evidence for sustained onward transmission in new co
      roosting host species.

PMID- 29355608
TI  - Genetic risk factors in thrombotic primary antiphospholipid syndrome: A
      systematic review with bioinformatic analyses.
AB  - BACKGROUND: Antiphospholipid Syndrome (APS) is an autoimmune multifactorial
      disorder. Genetics is believed to play a contributory role in the pathogenesis of
      APS, especially in thrombosis development and pregnancy morbidity. In the last 20
      years, extensive research on genetic contribution on APS indicates that APS is a
      polygenic disorder, where a number of genes are involved in the development of
      its clinical manifestations. AIMS: The aim of this systematic review is to
      evaluate the genetic risk factors in thrombotic primary APS. Additionally, to
      assess the common molecular functions, biological processes, pathways,
      interrelations with the gene encoded proteins and RNA-Seq-derived expression
      patterns over different organs of the associated genes via bioinformatic
      analyses. METHODS: Without restricting the year, a systematic search of English
      articles was conducted (up to 4th September 2017) using Web of Science, PubMed,
      Scopus, ScienceDirect and Google Scholar databases. Eligible studies were
      selected based on the inclusion criteria. Two researchers independently extracted
      the data from the included studies. Quality assessment of the included studies
      was carried out using a modified New-Castle Ottawa scale (NOS). RESULTS: From an
      initial search result of 2673 articles, 22 studies were included (1268 primary
      APS patients and 1649 healthy controls). Twenty-two genes were identified in
      which 16 were significantly associated with thrombosis in primary APS whereas six
      genes showed no significant association with thrombosis. Based on the NOS, 14
      studies were of high quality while 6 were low quality studies. From the
      bioinformatic analyses, thrombin-activated receptor activity (q = 6.77 * 10-7),
      blood coagulation (q = 2.63 * 10-15), formation of fibrin clot (q = 9.76 * 10-10)
      were the top hit for molecular function, biological process and pathway
      categories, respectively. With the highest confidence interaction score of 0.900,
      all of the thrombosis-associated gene encoded proteins of APS were found to be
      interconnected except for two. Based on the pathway analysis, cumulatively all
      the genes affect haemostasis [false discovery rate (FDR) = 1.01 * 10-8] and the
      immune system [FDR = 9.93 * 10-2]. Gene expression analysis from RNA-Seq data
      revealed that almost all the genes were expressed in 32 different tissues in the
      human body. CONCLUSION: According to our systematic review, 16 genes contribute
      significantly in patients with thrombotic primary APS when compared with
      controls. Bioinformatic analyses of these genes revealed their molecular
      interconnectivity in protein levels largely by affecting blood coagulation and
      immune system. These genes are expressed in 32 different organs and may pose
      higher risk of developing thrombosis anywhere in the body of primary APS
      patients.

PMID- 29355609
TI  - Is the Nociception Mechanism Altered in Offspring of Morphine-Abstinent Rats?
AB  - : To investigate the effect of parental drug abuse on children, nociception,
      electrophysiological alteration, mRNA expression of opioid receptors, and
      expression of certain intracellular proteins in offspring of morphine-abstinent
      rats were studied. Adult male and female animals received water-soluble morphine
      for 21 days. Ten days after the last morphine administration, animals were placed
      for mating in 4 groups as follows: healthy (drug naive) female and male, morphine
      abstinent female and healthy male, morphine-abstinent male and healthy female,
      morphine-abstinent male and morphine-abstinent female. Their adult male offspring
      were tested for nociception, neuronal discharge in nucleus accumbens (NAC) and
      prefrontal cortex (PFC). Our results showed that nociception in male offspring of
      all morphine-abstinent parent(s) groups was significantly reduced, compared with
      the control group. In the offspring of morphine-abstinent parent(s) groups,
      sensitivity to the antinociceptive effect of morphine was enhanced in chronic as
      well as in acute phases of the formalin test. Neuronal electrical activity
      reduced in the offspring of the morphine-exposed parent(s) in NAC as well as PFC
      regions. Moreover, our findings show that opioid receptors' expressions (u,
      kappa, and delta) increased in NAC of the litter of morphine-abstinent parent(s),
      compared with the control group. In addition, the expression of kappa receptors
      was remarkably increased in the PFC in morphine-abstinent parent group, relative
      to the control group. The phosphorylated levels of extracellular regulated kinase
      1/2 and cyclic adenosine monophosphate responsive element binding protein were
      significantly higher in the offspring of the morphine-abstinent parent(s) than
      the control group in the NAC. Our results indicated that endogenous opioid is
      altered in offspring of the morphine-exposed parent(s) and that heritage has a
      major role. PERSPECTIVE: This study showed that nociception was reduced in
      offspring of morphine-abstinent rat(s) and also these litters had a low level of
      neuronal firing rate, and enhanced opioid receptors expression, especially in the
      NAC. Because these offspring are more sensitive to the analgesic effect of
      morphine, clinicians should consider this issue to manage the dosage of morphine
      for treating pain in children with an abstinent parent(s).

PMID- 29355610
TI  - Maternal T-cell engraftment impedes with diagnosis of a SCID-ADA patient.
AB  - We describe the case of a child affected by severe combined immunodeficiency
      (SCID) with adenosine deaminase (ADA) deficiency showing a maternal T-cell
      engraftment, a finding that has never been reported before. The presence of
      engrafted maternal T cells was misleading. Although ADA enzymatic levels were
      suggestive of ADA-SCID, the child did not present the classical signs of ADA
      deficiency; therefore, the initial diagnosis was of a conventional SCID. However,
      ADA toxic metabolites and molecular characterization confirmed this diagnosis.
      Polyethylene glycol-modified bovine (PEG) ADA therapy progressively decreased the
      number of maternal engrafted T cells. The child was grafted with full bone marrow
      from a matched unrelated donor, after a reduced conditioning regimen, and the
      result was the complete immunological reconstitution.

PMID- 29355611
TI  - Evaluation of transient elastography in assessing liver fibrosis in patients with
      advanced schistosomiasis japonica.
AB  - Schistosomiasis remains an important public health issue. The presence and extent
      of liver fibrosis are associated with disease progression and prognosis. The
      study is aimed at exploring the value of liver stiffness measurement (LSM) by
      transient elastography in assessing liver fibrosis in patients with advanced
      schistosomiasis japonica. Seventy-three patients were consecutively recruited for
      the purpose of this study. The correlation between noninvasive parameters and
      histological fibrosis stages was analyzed and an area under receiver operating
      characteristic curve (AUROC) was used to assess diagnostic efficacy. Our results
      demonstrated that there are significant differences between LSM values of
      patients with different stages of fibrosis (F1 vs. F2, F2 vs. F3 and F3 vs. F4,
      P<0.01). The AUROC values of LSM in detecting significant fibrosis (F>=2),
      advanced fibrosis (F>=3) and cirrhosis (F=4) were 0.96, 0.90, and 0.92
      respectively. The optimal cut-off LSM values were 8.0kPa, 9.5kPa, and 18.0kPa for
      significant fibrosis, advanced fibrosis and cirrhosis. Based on differences
      between AUROC values, LSM was proven to be superior to several serum models in
      detecting advanced fibrosis and cirrhosis. In conclusion, our study demonstrates
      that LSM is a reliable parameter for assessing risk of liver fibrosis in patients
      with advanced schistosomiasis japonica.

PMID- 29355612
TI  - New record of Ascaridia nymphii (Secernentea: Ascaridiidae) from macaw parrot,
      Ara chloroptera, in China.
AB  - Present study was performed to identify the species of ascarids from macaw
      parrot, Ara chloroptera, in China. Total 6 ascarids (3 males and 3 females) were
      collected in the feces of 3 macaws at Guangzhou Zoo in Guangdong Province, China.
      Their morphological characteristics with dimensions were observed under a light
      microscope, and their genetic characters were analyzed with the partial 18S rDNA,
      ITS rDNA and nad4 gene sequences, respectively. Results showed that all worms
      have no interlabia but male worms have two alate spicules, well-developed
      precloacal sucker and a tail with ventrolateral caudal alae and 11 pairs of
      papillae. The partial 18S rDNA, ITS rDNA and nad4 sequences were 831bp, 1015bp
      and 394bp in length, respectively. They showed the highest similarity of 99.8%
      (18S rDNA) with Ascaridia nymphii, 93.8% identities (ITS rDNA) with A. columbae
      and 98.5% to 99.5% identities (nad4) with Ascaridia sp. from infected parrot. All
      Ascaridia nematodes from the macaws were clustered into one clade and formed
      monophyletic group of Ascaridia with A. columbae and A. galli in two phylogenetic
      trees. It is observed that the combining morphological and sequencing data from
      three loci, the present Ascaridia species was identified as Ascaridia nymphii,
      which is the first record of A. nymphii from macaw parrot in China.

PMID- 29355613
TI  - Histopathological growth patterns as a candidate biomarker for immunomodulatory
      therapy.
AB  - The encroachment of a growing tumor upon the cells and structures of surrounding
      normal tissue results in a series of histopathological growth patterns (HGPs).
      These morphological changes can be assessed in hematoxylin-and-eosin (H&E)
      stained tissue sections from primary and metastatic tumors and have been
      characterized in a range of tissue types including liver, lung, lymph node and
      skin. HGPs in different tissues share certain general characteristics like the
      extent of angiogenesis, but also appropriate tissue-specific mechanisms which
      ultimately determine differences in the biology of HGP subtypes. For instance, in
      the well-characterized HGPs of liver metastases, the two main subtypes,
      replacement and desmoplastic, recapitulate two responses of the normal liver to
      injury: regeneration and fibrosis. HGP subtypes have distinct cytokine profiles
      and differing levels of lymphocytic infiltration which suggests that they are
      indicative of immune status in the tumor microenvironment. HGPs predict response
      to bevacizumab and are associated with overall survival (OS) after surgery for
      liver metastases in colorectal cancer (CRC). In addition, HGPs can change over
      time in response to therapy. With standard scoring methods being developed, HGPs
      represent an easily accessible, dynamic biomarker to consider when determining
      strategies for treatment using anti-VEGF and immunomodulatory drugs.

PMID- 29355614
TI  - Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for
      immunomodulatory cancer treatments.
AB  - Head and neck squamous cell carcinoma (HNSCC) comprises a heterogeneous group of
      tumors that arise from the squamous epithelium of the oral cavity, oropharynx,
      larynx and hypopharynx. While many HNSCCs are related to classical etiologic
      factors of smoking and alcohol, a clinically, genomically, and immunologically
      distinct subgroup of tumors arise from the epithelium of the tonsil and the base
      of tongue as a result of infection with Human Papilloma Virus (HPV). In this
      review we describe the genomic and immunologic landscape of HNSCC, highlighting
      differences between HPV-positive and HPV-negative HNSCC. While HPV-negative
      tumors are characterized by tobacco-associated mutations in genes including TP53
      and CDKN2A, in HPV-positive HNSCC integration of viral genome from HPV into the
      host cellular genome results in expression of the E6 and E7 viral oncoproteins,
      with consequent degradation of p53 and functional inactivation of Rb. The immune
      microenvironment of HNSCC is characterized by changes in immune cell populations,
      immune checkpoints, as well as tumor or microenvironmental factors that alter the
      balance of the immune milieu in favor of immunosuppression, allowing tumor
      evasion and escape from immune surveillance. Immune therapies, in particular
      those targeting the PD1 receptor or its ligand PD-L1, including nivolumab,
      pembrolizumab, durvalumab, and atezolizumab have shown significant efficacy in
      subsets of patients with HNSCC. Current trials are evaluating the efficacy of
      these agents in combination with chemotherapy, radiotherapy and other immune
      therapies including CTLA-4 and IDO-1 inhibitors. While biomarkers including PD-L1
      expression, PD-L2 expression and the interferon-gamma gene signature show
      potential to predict benefit from checkpoint inhibitor therapy - it is hoped that
      improved understanding of the genomic and immune landscape will lead to ways to
      improved strategies to stratify patients and to select which HNSCC are most
      likely to benefit from these therapies.

PMID- 29355615
TI  - A Competing Risk Model of First Failure Site after Definitive Chemoradiation
      Therapy for Locally Advanced Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: The aim of the study was to build a model of first failure site-
      and lesion-specific failure probability after definitive chemoradiotherapy for
      inoperable NSCLC. METHODS: We retrospectively analyzed 251 patients receiving
      definitive chemoradiotherapy for NSCLC at a single institution between 2009 and
      2015. All patients were scanned by fludeoxyglucose positron emission
      tomography/computed tomography for radiotherapy planning. Clinical patient data
      and fludeoxyglucose positron emission tomography standardized uptake values from
      primary tumor and nodal lesions were analyzed by using multivariate cause
      specific Cox regression. In patients experiencing locoregional failure,
      multivariable logistic regression was applied to assess risk of each lesion being
      the first site of failure. The two models were used in combination to predict
      probability of lesion failure accounting for competing events. RESULTS:
      Adenocarcinoma had a lower hazard ratio (HR) of locoregional failure than
      squamous cell carcinoma (HR = 0.45, 95% confidence interval [CI]: 0.26-0.76, p =
      0.003). Distant failures were more common in the adenocarcinoma group (HR = 2.21,
      95% CI: 1.41-3.48, p < 0.001). Multivariable logistic regression of individual
      lesions at the time of first failure showed that primary tumors were more likely
      to fail than lymph nodes (OR = 12.8, 95% CI: 5.10-32.17, p < 0.001). Increasing
      peak standardized uptake value was significantly associated with lesion failure
      (OR = 1.26 per unit increase, 95% CI: 1.12-1.40, p < 0.001). The electronic model
      is available at http://bit.ly/LungModelFDG. CONCLUSIONS: We developed a failure
      site-specific competing risk model based on patient- and lesion-level
      characteristics. Failure patterns differed between adenocarcinoma and squamous
      cell carcinoma, illustrating the limitation of aggregating them into NSCLC.
      Failure site-specific models add complementary information to conventional
      prognostic models.

PMID- 29355616
TI  - Tattoo-Induced False-Positive FDG PET/CT Interpretation while Staging for Lung
      Cancer.

PMID- 29355617
TI  - Serine protease inhibitors containing a Kunitz domain: their role in modulation
      of host inflammatory responses and parasite survival.
AB  - Proteins containing a Kunitz domain have the typical serine protease inhibition
      function ranging from sea anemone to man. Protease inhibitors play major roles in
      infection, inflammation disorders and cancer. This review discusses the role of
      serine proteases containing a Kunitz domain in immunomodulation induced by
      helminth parasites. Helminth parasites are associated with protection from
      inflammatory conditions. Therefore, interest has raised whether worm parasites or
      their products hold potential as drugs for treatment of immunological disorders.
      Finally, we also propose the use of recombinant SmKI-1 from Schistosoma mansoni
      as a potential therapeutic molecule to treat inflammatory diseases.

PMID- 29355618
TI  - Lipopepsomes: A novel and robust family of nano-vesicles capable of highly
      efficient encapsulation and tumor-targeted delivery of doxorubicin hydrochloride
      in vivo.
AB  - Doxil(r) is the first FDA-approved anti-cancer nano-drug. Notably, no targeted
      liposomal formulation has advanced to clinical stage despite tremendous work
      undertaken, partly due to a low stability of liposomes. Here, we report on novel
      lipopepsomes self-assembled from poly(ethylene glycol)-b-poly(alpha-aminopalmitic
      acid) as a stable and versatile alternative to liposomes for highly efficient
      encapsulation and tumor-targeted delivery of doxorubicin hydrochloride (Dox.HCl).
      Interestingly, lipopepsomes could be easily decorated with 20mol% cRGD peptide
      and loaded with 17.4wt% Dox.HCl, giving cRGD-LPP-Dox with a small size of ~80nm.
      cRGD-LPP-Dox exhibited a high stability against 10% FBS and restrained drug
      release under physiological conditions. Flow cytometry, confocal microscopy and
      MTT assays using alphavbeta3-overexpressing A549 tumor cells showed obviously
      more efficient uptake and higher anticancer activity for cRGD-LPP-Dox than for
      non-targeted LPP-Dox and clinically used liposomal Dox (Lipo-Dox) controls.
      Notably, cRGD-LPP-Dox exhibited markedly enhanced toleration and tumor
      accumulation than Lipo-Dox. The therapeutic studies demonstrated that cRGD-LPP
      Dox achieved effective suppression of orthotopic A549 human lung tumor in nude
      mice, resulting in significantly improved survival rate as compared to LPP-Dox
      and Lipo-Dox groups. Lipopepsomes with small size, efficient loading of Dox.HCl,
      high stability and versatile ligand decoration have appeared as a highly
      attractive nanoplatform for targeted tumor chemotherapy.

PMID- 29355619
TI  - Nanotherapeutics in oral and parenteral drug delivery: Key learnings and future
      outlooks as we think small.
AB  - Nanotechnology ushered the field of medicine in to a new era. Miniaturization,
      increased surface area, and the unique physicochemical properties in the nano
      dimension were explored for new applications. Pharmaceutical industry picked up
      the technology and early success came fast for oral drug delivery through
      improvement in dissolution properties of the active molecules. Many products were
      launched using the nanocrystal technology on the oral side. Further development
      of polymeric nanoparticles led to wide spread research of nanocarriers for
      parenteral delivery. While considerable efforts have gone in the last two decades
      for testing nanoparticles for tumor targeting, delivery into tumors has remained
      challenging and suboptimal. Inadequate in vivo models that didn't accurately
      reflect the age and vascularity of human tumors, and inability to reproducibly
      target therapeutic drugs to the tissue of interest due to intrinsic
      biodistribution of the particles and hence side effects, limited the number of
      studies that advanced to the clinic. Our article addresses the questions commonly
      asked by scientific researchers in nanomedicine: "Has nanoparticle technology
      yielded on its initial promise that scientists predicted towards improving
      therapeutic index and avoid toxicity by delivering molecules to target tissues or
      was it more of wishful thinking that had several roadblocks?" We answer this
      question by linking the relevance of nanoparticles to cancer immunotherapy. The
      advent of immunotherapy has begun to show the potential applicability of
      nanoparticles in a different light, to target the immune system. In this
      approach, nanoparticles may positively influence the immune system rather than
      create the targeted "magic bullet". Utilizing the intrinsic properties of
      nanoparticles for immune targeting as opposed to targeting the tumor can bring
      about a positive difference due to the underlying complex cancer mechanisms that
      can potentially overlap with the heterogeneous biodistribution of nanoparticles
      towards improving the acquired and innate immune responses. In this review, we
      have followed the progress of nanotechnology in pharmaceutical applications with
      key insights from oral and parenteral drug delivery, and how to modify our
      thinking to better utilize nanoparticles for immuno-oncology. In contrast to
      conventional "local" tumor targeting by nanoparticles, we propose a new mechanism
      whereby nanoparticles trigger priming of the T cells towards tumor destruction.
      The heterogenous biodistribution of nanoparticles lends itself to stimulating
      immune cells systemically in a "global" manner and with the right therapeutic
      combinations will be able to trigger tumor antigens to continually activate,
      retain memory effects and destroy tumor cells.

PMID- 29355620
TI  - Impact of different hydrophobic ion pairs of octreotide on its oral
      bioavailability in pigs.
AB  - : The objective of this study was to investigate the impact of different
      hydrophobic ion pairs (HIP) on the oral bioavailability of the model drug
      octreotide in pigs. Octreotide was ion paired with the anionic surfactants
      deoxycholate, decanoate and docusate differing in lipophilicity. These
      hydrophobic ion pairs were incorporated in self-emulsifying drug delivery systems
      (SEDDS) based on BrijO10, octyldodecanol, propylene glycol and ethanol in a
      concentration of 5mg/ml. SEDDS were characterized regarding size distribution,
      zeta potential, stability towards lipase, log DSEDDS/release medium and mucus
      diffusion behavior. The oral bioavailability of octreotide was evaluated in pigs
      via LC-MS/MS analyses. Most efficient ion pairing was achieved at a molar ratio
      of 1:3 (peptide: surfactant). SEDDS containing the octreotide-deoxycholate, 
      decanoate and -docusate ion pair exhibited a mean droplet size of 152nm, 112nm
      and 191nm and a zeta potential of -3.7, -4.6 and -5.7mV, respectively. They were
      completely stable towards degradation by lipase and showed a log DSEDDS/release
      medium of 1.7, 1.8 and 2.7, respectively. The diffusion coefficient of these
      SEDDS was in the range of 0.03, 0.11 and 0.17*10-9cm2/s, respectively. In vivo
      studies with these HIPs showed no improvement in the oral bioavailability in case
      of octreotide-decanoate. In contrast, octreotide-deoxycholate and octreotide
      docusate SEDDS resulted in a 17.9-fold and 4.2-fold higher bioavailability vs.
      CONTROL: According to these results, hydrophobic ion pairing could be identified
      as a key parameter for SEDDS to achieve high oral bioavailability.

PMID- 29355621
TI  - In vitro model for predicting bioavailability of subcutaneously injected
      monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs), which are now more frequently administered by
      subcutaneous (SC) injection rather than intravenously, have become a tremendously
      successful drug format across a wide range of therapeutic areas. Preclinical
      evaluations of mAbs to be administered by SC injection are typically performed in
      species such as mice, rats, minipigs, and cynomolgus monkeys to obtain critical
      information regarding formulation performance and prediction of PK/PD outcomes
      needed to select clinical doses for first-in-human studies. Despite extensive
      efforts, no preclinical model has been identified to date that accurately
      predicts clinical outcomes for these SC injections. We have addressed this
      deficiency with a novel in vitro instrument, termed Scissor, to model events
      occurring at the SC injection site and now further validated this approach using
      a set of eight mAbs for which clinical PK/PD outcomes have been obtained.
      Diffusion of these mAbs from the Scissor system injection cartridge into a large
      volume physiological buffer, used to emulate mAb movement from the SC injection
      site into the systemic circulation, provided distinct profiles when monitored
      over a 6h period. Curve-fitting analysis of these profiles using the Hill
      equation identified parameters that were used, along with physicochemical
      properties for each mAb, in a partial least squares analysis to define a
      relationship between molecule and formulation properties with clinical PK
      outcomes. The results demonstrate that parameters of protein charge at neutral pH
      and isoelectric point (pI) along with combined formulation properties such as
      viscosity and mAb concentration can dictate the movement of the mAb from the
      injection cartridge to infinite sink compartment. Examination of profile
      characteristics of this movement provided a strong predictive correlation for
      these eight mAbs. Together, this approach demonstrates the feasibility of this in
      vitro modelling strategy as a tool to identify drug and formulation properties
      that can define the performance of SC injected medicines and provide the
      potential for predicting clinical outcomes that could be useful for formulation
      selection and a first-in-human clinical dosing strategy.

PMID- 29355622
TI  - An indoleamine 2, 3-dioxygenase siRNA nanoparticle-coated and Trp2-displayed
      recombinant yeast vaccine inhibits melanoma tumor growth in mice.
AB  - Therapeutic vaccine is a promising approach in cancer therapy. But tumor
      associated antigen peptides have weak immunogenicity and cancer patients are
      often characterized by immunosuppression and tolerance, leading to less
      efficiency of immunotherapy. We here successfully developed indoleamine 2, 3
      dioxygenase (IDO) siRNA nanoparticle-coated and tyrosinase-related protein 2
      (Trp2)-displayed recombinant Saccharomyces cerevisiae (YCP). YCPs had positive
      charges with a diameter of approximately 5MUm, resulting in selective
      phagocytosis by APC cells. YCP-delivered siRNA and Trp2 successfully escaped from
      phagosomes, efficiently inhibited IDO expression in DCs, promoted the immune
      reaction of T cell against Trp2, increased the secretion of proinflammatory
      cytokines such as IFN-gamma,TNF-alpha, and IL-6, and decreased the generation of
      regulatory T cells. Moreover, YCPs significantly inhibited melanoma tumor growth
      by alleviating immune tolerance and promoting Trp2-specific CD8+ T cell immune
      response. These results suggest that Saccharomyces cerevisiae as a combined
      immunotherapeutic platform to simultaneously delivery IDO-siRNA and Trp2 epitope
      peptide is a promising vaccine system for melanoma treatment.

PMID- 29355623
TI  - Cytotoxic and anti-kinetoplastid potential of the essential oil of Alpinia
      speciosa K. Schum.
AB  - Alpinia speciosa K. Schum, known as colonia (colony), is native to tropical Asia
      and found in parts of tropical America. Its leaves are used to wrap food,
      rhizomes for food preparation and seeds for health maintenance, and have been
      widely used by the population as a diuretic, antihypertensive, antiulcerogenic
      and sedative. The present study aimed to verify the leishmanicidal and
      trypanocidal potential, as well as the cytotoxicity, of the A. speciosa essential
      oil, in vitro. A. speciosa presented 1,8-cineole (28.46%), camphor (17.10%) and
      sabinene (9.95%) as major constituents. The cytotoxic activity of the essential
      oil presented a low value, while the antipromastigote and antiepimastigote
      activity presented values considered clinically relevant, since it had an action
      below 500 MUg/mL. In relation to this study, it can be concluded that this is a
      pioneer in the potential of the A. speciosa essential oil and in the use against
      the parasites Trypanosoma cruzi Chagas and Leishmania brasiliensis Vianna, having
      its importance also rooted in this fact. Still in accordance with the results, A.
      speciosa was effective because it presented values of clinical relevance and low
      toxicity. It was also observed that the chemical constitution of the above
      identified compounds with remarkable antiparasitic activities.

PMID- 29355624
TI  - Updated procedure for the safety evaluation of natural flavor complexes used as
      ingredients in food.
AB  - An effective and thorough approach for the safety evaluation of natural flavor
      complexes (NFCs) was published in 2005 by the Expert Panel of the Flavor and
      Extract Manufacturers Association (FEMA). An updated procedure is provided here,
      which maintains the essential concepts of the use of the congeneric group
      approach and the reliance on the threshold of toxicological concern (TTC)
      concept. The updated procedure emphasizes more rigorous considerations of
      unidentified constituents and the genotoxic potential of constituents. The update
      of the previously established procedure is the first step in a multi-year project
      to conduct safety re-evaluations for more than 250 NFCs that have uses that are
      currently considered Generally Recognized as Safe (GRAS) by the FEMA Expert
      Panel. In addition, this procedure can be more generally employed in the safety
      evaluation of NFCs.

PMID- 29355625
TI  - Bi-functional fusion enzyme EG-M-Xyn displaying endoglucanase and xylanase
      activities and its utility in improving lignocellulose degradation.
AB  - In this study, the gene fusion of endoglucanase (EG, one of cellulases) from
      Teleogryllus emma and xylanase (Xyn, one of hemicellulases) from Thermomyces
      lanuginosus was constructed to generate a fusion enzyme (EG-M-Xyn). Through the
      expression and purification by ultrafiltration and size-exclusion chromatography,
      the purified EG-M-Xyn had a molecular weight of 75.5 kDa and exhibited the
      specific activity of CMCase and xylanase as 306.8 U/mg and 1227.3 U/mg,
      respectively. The Km values (CMC and beechwood xylan) were 6.8 and 60.6 mg mL-1
      while catalytic efficiency (kcat/Km) values of CMCase and xylanase were 3280 and
      38,797 min-1 mg-1 mL, respectively. EG-M-Xyn exerted great properties for its
      great potential in improving the enzymatic hydrolysis of lignocellulosics to
      produce fermentable sugars. First, EG-M-Xyn showed mild reaction pH and
      temperature of 5.5 and 50  degrees C, respectively. Secondly, EG-M-Xyn exhibited
      great heat tolerance of T1/2 values of 173 (CMCase) and 693 min (xylanase).
      Lastly and most importantly, application of EG-M-Xyn in combination with Ctec2
      (commercial enzyme) in the saccharification led to a 10-20% net increase in
      fermentable sugars liberated from pretreated rice straw in comparison to the
      Ctec2 alone group. In conclusion, EG-M-Xyn had great potential in generating
      fermentable sugars from renewable agro-residues for biofuel and fine chemical
      industry.

PMID- 29355626
TI  - Transgenerational endotoxin tolerance-like effect caused by paternal dietary
      Astragalus polysaccharides in broilers' jejunum.
AB  - To learn the nutri-epigenetics role of Astragalus polysaccharides (APS), we
      designed and studied the transgenerational effect of paternal dietary APS
      supplementation in chickens. 160 Avein breeder cocks were randomly allocated into
      5 groups and fed with 0, 0.01, 0.1, 1, and 10 g/kg APS supplement, respectively.
      Sperm of breeder cocks was collected and used for hatching experiment to get
      broiler chickens when the cocks at 40-weeks-old. It showed that the paternal
      dietary 10 g/kg APS could transgenerational promote growth performance and
      jejunal tissue morphology of chickens. As to phenotypes, 10 g/kg APS treatment
      was chosen for molecular assays. In jejunal mucosa, 10 g/kg dietary APS didn't
      have any systematic effect on gene transcription of breeder cocks, whereas, the
      APS could induce transgenerational endotoxin tolerance-like effect through
      activating the IFNalpha-SOCS1 pathway in chicks. In both jejunum and sperm, the
      promoter methylation level of SOCS1 significantly reduced in 10 g/kg APS
      treatment versus the control group. In addition, the paternal APS significantly
      affected histone modification in promotor region of TRIF. Our data revealed that
      the paternal dietary APS supplementation could induce transgenerational endotoxin
      tolerance-like effect in jejunum mucosa of broiler chickens. And nutri-epigenetic
      modifications are crucial for this transgenerational effect.

PMID- 29355627
TI  - Preparation and antioxidant activities of important traditional plant
      polysaccharides.
AB  - Polysaccharides are widely found in nature, mainly divided into three kinds of
      plant polysaccharides, animal polysaccharides and microbial polysaccharides. In
      recent years, the antioxidant activity of polysaccharide has become a hot spot in
      the field of polysaccharide research. Polysaccharide is one of the active
      ingredients of many medicines, which has the functions of increasing antioxidant
      enzyme activity, eliminating free radicals, inhibiting lipid peroxidation and
      protecting the biofilm, anti-oxidation and anti-aging effects. The preparation
      methods, main chemical structures and antioxidant activities of important
      traditional plant polysaccharides from different sources were investigated and
      discussed.

PMID- 29355628
TI  - Chitosan-coated cotton cloth supported copper nanoparticles for toxic dye
      reduction.
AB  - A new route to fabricate cotton cloth (CC) as easily removable substrate for the
      synthesis of copper nanoparticles on its surface and its utilization in a toxic
      dye reduction is reported herein. A 1 wt% chitosan (Chi) aqueous solution was
      prepared and coated onto CC surface to prepare the ions affinity Chi-CC material.
      The Chi-CC was then kept in copper sulphate solution with three different
      concentrations (0.05 M, 0.1 M and 0.2 M) to interact with Cu2+ ions through -NH
      and -OH functional groups of the Chi chain. After sufficient time of the Cu2+
      uptake, the Chi-CC was treated with 0.1 M NaBH4 solution which turned its color
      indicating well organization of the adsorbed ions into Cu-nanoparticles. The bare
      CC, Chi-CC and Cu/Chi-CC were spectroscopically examined via scanning electron
      microscopy, X-ray diffractometry, energy dispersive X-ray spectroscopy and thermo
      gravimetric analysis. Afterward, Cu/Chi-CC was used in the Congo red (CR) dye
      reduction by NaBH4 as catalyst. The performance of the amount of the catalyst and
      its usage in a series of similar dye reduction was evaluated.

PMID- 29355629
TI  - Sulfated Laminaria japonica polysaccharides inhibit macrophage foam cell
      formation.
AB  - In this work, a purified Laminaria japonica polysaccharide (LJP61A) was
      chemically modified to obtain three sulfated polysaccharides (SLJP1, SLJP2 and
      SLJP3) with different degrees of sulfation using the method of chlorosulfonic
      acid/pyridine. The effects and underlying mechanism of SLJP1, SLJP2 and SLJP3 on
      the suppression of macrophage foam cell formation were further investigated using
      the model of oxidized low-density lipoprotein (ox-LDL)-induced foam cell
      formation. Results exhibited that the macrophage foam cell formation induced by
      ox-LDL could be significantly alleviated by these sulfated polysaccharides in a
      dose-dependent manner. Meanwhile, the enhancement of PPAR-gamma mRNA expression
      in ox-LDL induced macrophages was remarkably inhibited by these sulfated
      polysaccharides. Moreover, the cellular inflammation induced by ox-LDL could also
      be remarkably mitigated by these sulfated polysaccharides. These results
      indicated that the sulfated L. japonica polysaccharides could inhibit the
      conversion of macrophage into foam cell via obstructing PPAR-gamma activation and
      alleviating cellular inflammation.

PMID- 29355630
TI  - Fabrication of cationic nanostructures from short self-assembling amphiphilic
      mixed alpha/beta-pentapeptide: Potential candidates for drug delivery, gene
      delivery, and antimicrobial applications.
AB  - The present article describes designing and fabrication of nanostructures from a
      mixed alpha/beta-pentapeptide, Lys-betaAla-betaAla-Lys-betaAla, which majorly
      contains non-natural beta-alanine residues in the backbone with two alpha-lysine
      residues at 1- and 4-positions. The amphiphilic pentapeptide showed the ability
      to self-assemble into cationic nanovesicles in an aqueous solution. The average
      size of peptide nanostructures was found to be ~270 nm with a very high cationic
      charge of ~+40 mV. TEM micrographs revealed the average size of the same
      nanostructures ~80 nm bearing vesicular morphology. CD and FTIR spectroscopic
      studies on self-assembled pentapeptide hinted at random coil conformation which
      was also correlated with conformational search program using Hyper Chem 8.0. The
      pentapeptide nanostructures were then tested for encapsulation of hydrophobic
      model drug moieties, L-Dopa, and curcumin. Transfection efficiency of the
      generated cationic nanostructures was evaluated on HEK293 cells and compared the
      results with those obtained in the presence of chloroquine. The cytotoxicity
      assay performed using MTT depicted ~75-80% cell viability. The obtained
      nanostructures also gave positive results against both Gram-negative and Gram
      positive bacterial strains. Altogether the results advocate the promising
      potential of the pentapeptide foldamer, H-Lys-betaAla-betaAla-Lys-betaAla-OEt,
      for drug and gene delivery applications along with the antimicrobial activity.

PMID- 29355631
TI  - Expression and Purification of Quinine Dihydro Pteridine Reductase from
      astrocytes and its significance in the astrocyte pathology.
AB  - Quinine dihydropteridinereductase (QDPR) is involved in the synthesis of
      tetradihydrobiopteridine (BH4) that serve as cofactor for many aromatic
      hydroxylases including induced nitric oxide synthase (NOS) leading to NO
      production. Increased activity of QDPR has been associated with decrease levels
      of TGF-beta, a cytokine that regulates the immune response and that elevated
      levels of NO has been associated with neurodegenerative diseases. Thus,
      expression of QDPR in astrocytes is essential to study the pathological changes
      observed in many neurodegenerative disorders. We have expressed QDPR in
      astrocytes and generated stably expressing clones that overexpresses QDPR. We
      further verified the specificity of QDPR expression using immunofluorescence and
      immunoblotting. To further confirm, we purified QDPR using Ni-NTA column and
      subjected the purified fraction to immunoblotting using anti-QDPR antibody and
      identified two major protein products of QDPR resolving at 25 and 17 kDa as
      reported in the literature. In order to further assess the significance of QDPR
      expression, we verified the expression of iNOS in QDPR over expressing cells. We
      show for the first time statistically significant up regulation of iNOS in QDPR
      overexpressing astrocytes. Increased expression of iNOS associated with astrocyte
      pathology seen in many neurodegenerative disorders may have implications in
      autoimmune neurodegenerative disorders.

PMID- 29355632
TI  - In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic
      toxicity studies of orally administered methotrexate loaded chitin nanogel in
      comparison with methotrexate tablet.
AB  - The anti-psoriatic efficacy of orally administered methotrexate loaded chitin
      nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and
      compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG
      at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti
      psoriatic activity which is very much comparable with MTX, caused normalization
      of histological features and inflammatory score associated with induced
      psoriasis. Biodistribution studies revealed the presence of drug in serum and in
      vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg
      dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at
      the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub
      acute toxicity studies and MTX tablet was found to be toxic on liver and lung on
      sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub
      acute and sub chronic administrations, suggesting that it can provide sufficient
      serum and tissue level of methotrexate necessary to clear psoriatic lesions,
      without inducing systemic toxicity and expected to be a better alternative for
      orally administered conventional methotrexate tablet for patients who need
      systemic medications for psoriasis.

PMID- 29355633
TI  - Characterization of poly-d-mannuronate and poly-l-guluronate block fractions from
      sodium alginate and preparation of hydrogels with poly(vinylalcohol).
AB  - Sodium salts of homopoly-d-mannuronic acid (MM) and of homopoly-l-guluronic acid
      (GG) from sodium alginates were characterized by NMR relaxometry. Determination
      of NMR spin-lattice and spin-spin relaxation times of water proton in
      homopolymeric block solutions and hydrogels indicated differences in
      homopolymeric blocks tertiary structure. Hydrogels of MM or GG blocks and
      poly(vinyl alcohol) (PVA) were prepared by freeze-thawing cycles method; their
      swelling properties and sensitivity to pH stimuli were assayed in control
      delivery of a model drug. MM/PVA hydrogels show better metformin release
      characteristics than GG/PVA hydrogels. It was found that release of the drug at
      pH 1.2 from hydrogels was minor to 5%. At the release equilibrium, 60 and 55% of
      the drug encapsulated were release from MM/PVA and GG/PVA hydrogels,
      respectively. Also, the release of metformin from hydrogels was studied by 1H NMR
      spectroscopy showing that 40 and 36% of drug were released after 4 h from MM/PVA
      and GG/PVA hydrogels, respectively.

PMID- 29355634
TI  - Electromagnetic manipulation enabled calcium alginate Janus microsphere for
      targeted delivery of mesenchymal stem cells.
AB  - We prepared Janus microspheres based on sodium alginate for the encapsulation of
      mesenchymal stem cells (MSC) in one compartment and iron oxide nanoparticles
      (IONP) or a drug in the second compartment. 4% percent sodium alginate solution
      was allowed to pass through a septum-theta capillary device and react with 2.5%
      calcium chloride to allow crosslinking to occur in the solution, forming calcium
      alginate Janus microspheres. Physico-chemical characterization of microspheres
      was done by FTIR, TGA, and XRD after loading of stem cells and IONP/drug. The
      mechanical integrity of microspheres was tested at different time points, which
      showed that 4% alginate microspheres were mechanically stable for a long period
      of time. Live/dead staining of MSCs alone and the MTS assay of MSCs and DMSO co
      loaded were performed, which showed less toxicity to MSC in the Janus
      configuration. IONP/MSC-loaded Janus microspheres were tested by magnetic
      manipulation for targeted MSC delivery for cartilage repair using an
      electromagnetic manipulation (EMM) device. Janus microspheres can be used for
      targeted stem cell/drug delivery using EMM for cartilage repair in the near
      future.

PMID- 29355635
TI  - Extraction, characterisation and antioxidant activity of polysaccharides from
      Chinese watermelon.
AB  - Extraction and antioxidant activity of polysaccharides from the Chinese
      watermelon was investigated. The polysaccharides were obtained by hot water
      extraction, ethanol precipitation, and deproteinization with HCl, respectively.
      The molecular weight was 3.02 * 104. It showed by high performance liquid
      chromatography (HPLC) and TLC that Chinese watermelon polysaccharides consisted
      of six monosaccharides, namely glucose, galactose, mannose, xylose, arabinose,
      and rhamnose. The polysaccharides contained the beta-glycosidic bond. Moreover,
      it was proved that the polysaccharides had high scavenging ability to superoxide
      anions.

PMID- 29355636
TI  - Expression and characterization of a kappa-carrageenase from marine bacterium
      Wenyingzhuangia aestuarii OF219: A biotechnological tool for the depolymerization
      of kappa-carrageenan.
AB  - kappa-Carrageenases are desirable tools for tailoring the molecular weight,
      physicochemical properties and functionalities of kappa-carrageenan, a
      macromolecule widely utilized in various industries. In this study, a novel GH16
      family kappa-carrageenase, designated as Cgk16A, was cloned from the genome of
      marine bacterium Wenyingzhuangia aestuarii OF219 and expressed in Escherichia
      coli. Its biochemical properties, kinetic parameters and hydrolytic pattern were
      characterized. The enzyme demonstrated a low optimal reaction temperature (25 
      degrees C) and a cold-adapted feature. As an endo-acting glycoside hydrolase,
      Cgk16A degraded kappa-carrageenan in a random manner, and it was competent to
      prepare the degradation products with varying degrees of polymerization. The mass
      spectrometry analysis revealed that the end products of Cgk16A were majorly
      composed of kappa-carrageenan tetrasaccharide with a minor portion of
      disaccharide. The enzyme showed higher enzyme-substrate affinity over all
      hitherto characterized GH16 kappa-carrageenases, indicated by its low Km value
      (0.17 MUM). Cgk16A could be employed as a potential biotechnological tool for
      depolymerizing kappa-carrageenan, which would facilitate the future application
      of kappa-carrageenan and its degradation products.

PMID- 29355637
TI  - Improving the thermostability by introduction of arginines on the surface of
      alpha-L-rhamnosidase (r-Rha1) from Aspergillus niger.
AB  - To improve the thermostability of alpha-L-rhamnosidase (r-Rha1), an enzyme
      previously identified from Aspergillus niger JMU-TS528, multiple arginine (Arg)
      residues were introduced into the r-Rha1 sequence to replace several lysine (Lys)
      residues that located on the surface of the folded r-Rha1. Hinted by in silico
      analysis, five surface Lys residues (K134, K228, K406, K440, K573) were targeted
      to produce a list of 5 single-residue mutants and 4 multiple-residue mutants
      using site-directed mutagenesis. Among these mutants, a double Lys to Arg mutant,
      i.e. K406R/K573R, showed the best thermostability improvement. The half-life of
      this mutant's enzyme activity increased 3 h at 60  degrees C, 23 min at 65 
      degrees C, and 3.5 min at 70  degrees C, when compared with the wild type. The
      simulated protein structure based interaction analysis and molecular dynamics
      calculation indicate that the thermostability improvement of the mutant K406R
      K573R was possibly due to the extra hydrogen bonds, the additional cation-pi
      interactions, and the relatively compact conformation. With the enhanced
      thermostability, the alpha-L-rhamnosidase mutant, K406R-K573R, has potentially
      broadened the r-Rha1 applications in food processing industry.

PMID- 29355638
TI  - Biological macromolecules based targeted nanodrug delivery systems for the
      treatment of intracellular infections.
AB  - Intracellular infections are tricky to treat, the reason being the poor
      penetration of antibiotics/antimycotics into the microbial niche (host cell).
      Macrophages are primary targets of facultative and obligate intracellular
      bacteria/fungi to be abused as host cells. The need for drugs with better
      intracellular penetration led to the development of endocytosable drug carriers,
      which can cross the cell membrane of the host cells (macrophages) by imitating
      the entry path of the pathogens. Therefore, the drugs can be targeted to
      macrophages ensuring enhanced therapeutic effect. This review discusses the
      exploitation of various nanocarriers for targeted delivery of drugs to the
      macrophages in the last two decades.

PMID- 29355639
TI  - Preparation and characterization of carboxymethyl chitosan sulfate/oxidized
      konjac glucomannan hydrogels.
AB  - Hydrogel wound dressing is a new type of biomaterial with performance that is
      better than traditional and biological dressings. It has been extensively
      researched and the application in the field of biomedicine is common. In this
      study, we developed a simple and nontoxic method for preparing a new type of
      composite hydrogel, which formed through the Schiff-base reaction between the
      aldehyde of oxidized konjac glucomannan (OKGM) and the amino of carboxymethyl
      chitosan sulfate (CMSS). The chemical structures of this composite hydrogel were
      characterized by transform infrared spectroscopy (FT-IR). The micro-morphology of
      hydrogels were analyzed by scanning electron microscopy (SEM). Meanwhile, the
      properties of composite hydrogels including gelation time, swelling ability,
      water evaporation rate, hemolytic potential and biological compatibility were
      also investigated in different means. The results gained from these studies show
      that this composite hydrogels have a series of properties such as short gelation
      time, good swelling ability, appropriate water evaporation rate, excellent
      hemocompatibility and well biological compatibility. Considering these excellent
      performance, this composite hydrogels can be used as a wound dressing to treat
      injured skin.

PMID- 29355640
TI  - Cannabinoids induce apathetic and impulsive patterns of choice through CB1
      receptors and TRPV1 channels.
AB  - Despite evidence from psychiatry and psychology clinics pointing to altered
      cognition and decision making following the consumption of cannabis, the effects
      of cannabis derivatives are still under dispute and the mechanisms of cannabinoid
      effects on cognition are not known. In this study, we used effort-based and delay
      based decision tasks and showed that ACEA, a potent cannabinoid agonist induced
      apathetic and impulsive patterns of choice in rats in a dose-dependent manner
      when locally injected into the anterior cingulate cortex (ACC) and orbitofrontal
      cortex (OFC), respectively. Pre-treatment with AM251, a selective cannabinoid
      type 1 (CB1) receptor antagonist, reversed ACEA-induced impulsive and apathetic
      patterns of choice in doses higher than a minimally effective dose. Unlike CB1
      receptor antagonist, pretreatment with capsazepine, a transient receptor
      potential vanilloid type 1 (TRPV1) channel antagonist, was effective only at an
      intermediary dose. Furthermore, capsazepine per se induced impulsivity and apathy
      at a high dose suggesting a basal tonic activation of TRPV1 channels that exist
      in the ACC and OFC to support cost-benefit decision making and to help avoid
      apathetic and impulsive patterns of decision making. Taken together, unlike
      previous reports supporting opposing roles for the CB1 receptors and TRPV1
      channels in anxiety and panic behavior, our findings demonstrate a different sort
      of interaction between endocannabinoid and endovanilloid systems and suggest that
      both systems contribute to the cognitive disrupting effects of cannabinoids.
      Given prevalent occurrence of apathy and particularly impulsivity in psychiatric
      disorders, these results have significant implications for pharmacotherapy
      research targeting these receptors.

PMID- 29355642
TI  - Calpastatin ablation aggravates the molecular phenotype in cell and animal models
      of Huntington disease.
AB  - Deciphering the molecular pathology of Huntington disease is of particular
      importance, not only for a better understanding of this neurodegenerative
      disease, but also to identify potential therapeutic targets. The polyglutamine
      expanded disease protein huntingtin was shown to undergo proteolysis, which
      results in the accumulation of toxic and aggregation-prone fragments. Amongst
      several classes of proteolytic enzymes responsible for huntingtin processing, the
      group of calcium-activated calpains has been found to be a significant mediator
      of the disease protein toxicity. To confirm the impact of calpain-mediated
      huntingtin cleavage in Huntington disease, we analysed the effect of depleting or
      overexpressing the endogenous calpain inhibitor calpastatin in HEK293T cells
      transfected with wild-type or polyglutamine-expanded huntingtin. Moreover, we
      crossbred huntingtin knock-in mice with calpastatin knockout animals to assess
      its effect not only on huntingtin cleavage and aggregation but also additional
      molecular markers. We demonstrated that a reduced or ablated expression of
      calpastatin triggers calpain overactivation and a consequently increased mutant
      huntingtin cleavage in cells and in vivo. These alterations were accompanied by
      an elevated formation of predominantly cytoplasmic huntingtin aggregates. On the
      other hand, overexpression of calpastatin in cells attenuated huntingtin
      fragmentation and aggregation. In addition, we observed an enhanced cleavage of
      DARPP-32, p35 and synapsin-1 in neuronal tissue upon calpain overactivation. Our
      results corroborate the important role of calpains in the molecular pathogenesis
      of Huntington disease and endorse targeting these proteolytic enzymes as a
      therapeutic approach.

PMID- 29355643
TI  - A penicillin skin testing initiative in an outpatient allergy office.

PMID- 29355644
TI  - The Cost of Self-Reported Penicillin Allergy: A Systematic Review.
AB  - BACKGROUND: Patients who report a penicillin (PCN) allergy receive suboptimal
      antibiotic therapy compared with patients not reporting an allergy. However, a
      majority of patients who report PCN allergy are not truly allergic on
      confirmatory testing. Ruling out PCN allergy by testing may improve clinical and
      economic outcomes for patients with reported allergies requiring antibiotic
      therapy. OBJECTIVE: The objective of this study was to summarize clinical and
      economic outcomes associated with PCN allergy and provide recommendations for
      future cost-effectiveness analyses for PCN allergy testing. METHODS: A literature
      search was conducted using SCOPUS, EMBASE, and PubMed, including all articles
      published any date through April 25, 2017 (PROSPERO Registration number
      42017064112). A total of 1518 abstracts were found during the initial search with
      96 duplicates, for a total of 1422 articles for screening. Thirty articles were
      included for qualitative synthesis and full data extraction. RESULTS: The
      majority of the studies included had an observational design focusing on
      inpatient admissions. The most frequently measured outcome in the context of PCN
      allergy was optimizing antibiotic therapy. Patients with PCN allergy were found
      to have direct drug costs during inpatient admission ranging from no difference
      to an additional $609/patient compared with patients without PCN allergy.
      Outpatient prescription costs were estimated from $14 to $193/patient higher for
      PCN allergic patients. Total inpatient costs were less for patients without PCN
      allergy with average savings from $1145 to $4254/patient. CONCLUSIONS:
      Evaluations of clinical and economic outcomes of PCN allergy are primarily
      observational and focus on inpatient populations. Long-term relationships between
      PCN allergy and clinical and economic outcomes are unknown.

PMID- 29355645
TI  - Errors in the Use of Inhalers by Health Care Professionals: A Systematic Review.
AB  - BACKGROUND: Inefficient inhaler technique (IT) compromises the optimal delivery
      of medication. However, the IT knowledge of health care professionals (HCPs) has
      received scant attention. OBJECTIVE: The objective of this study was to perform a
      systematic review of published reports assessing the IT proficiency of HCPs in
      using pressurized metered dose (pMDI) and dry powder (DPI) inhalers. METHODS:
      Studies published between 1975 and 2014 that directly assessed the IT skills of
      HCPs were selected according to predefined selection criteria. RESULTS: Data were
      extracted from 55 studies involving 6,304 HCPs who performed 9,996 tests to
      demonstrate their IT proficiency. Overall, the IT was considered correct in 15.5%
      of cases (95% confidence interval [CI], 12-19.3), decreasing over time from 20.5%
      (95% CI, 14.9-26.8) from the early period (defined as 1975-1995) to 10.8% (95%
      CI, 7.3-14.8) during the late period (1996-2014). The most common errors in the
      use of pMDIs were as follows: not breathing out completely before inhalation
      (75%; 95% CI, 56-90), lack of coordination (64%; 95% CI, 29-92), and
      postinhalation breath-hold (63%; 95% CI, 52-72). The most common errors using DPI
      were deficient preparation (89%; 95% CI, 82-95), not breathing out completely
      before inhalation (79%; 95% CI, 68-87), and no breath-hold (76%; 95% CI, 67-84).
      CONCLUSIONS: HCPs demonstrated inadequate knowledge of the proper use of
      inhalers. The poor understanding of the correct use of these devices may prevent
      these professionals from being able to adequately assess and teach proper
      inhalation techniques to their patients.

PMID- 29355641
TI  - The nicotinic receptor drug sazetidine-A reduces alcohol consumption in mice
      without affecting concurrent nicotine consumption.
AB  - Alcohol and nicotine addiction are frequently co-morbid. The nicotinic
      acetylcholine receptors (nAChRs) are critical for both alcohol and nicotine
      addiction mechanisms, since nAChR drugs that reduce nicotine consumption have
      been shown to also reduce alcohol consumption. Sazetidine-A, a pre-clinical nAChR
      drug with agonist and desensitizing effects at alpha4beta2 and alpha7 nAChRs, has
      been reported to reduce alcohol consumption and nicotine self-administration in
      rats when administered at high doses. However, this effect has not been
      replicated in mice. In this study, we examined the effect of sazetidine-A on
      alcohol and nicotine consumption in male and female mice utilizing voluntary oral
      consumption procedures previously developed in our lab. We found that sazetidine
      A (1 mg/kg, i.p) reduced overnight alcohol consumption, but did not affect
      nicotine consumption when presented either alone or concurrently with alcohol.
      Sazetidine-A did not reduce water or saccharin consumption at any dose tested. In
      a chronic co-consumption experiment in which either alcohol or nicotine was re
      introduced after one week of forced abstinence, sazetidine-A attenuated post
      abstinence consumption of alcohol but not nicotine. Sazetidine-A also
      significantly reduced alcohol consumption in an acute, binge drinking-in-the-dark
      procedure. Finally, we tested the effect of sazetidine-A on alcohol withdrawal,
      and found that sazetidine-A significantly reduced handling-induced convulsions
      during alcohol withdrawal. Collectively, these data suggest a novel role for the
      nAChR targets of sazetidine-A in specifically mediating alcohol consumption,
      separate from the involvement of nAChRs in mediating nicotine consumption.
      Delineation of this pathway may provide insight into novel therapies for the
      treatment of alcohol use disorders.

PMID- 29355646
TI  - Consciousness and confidence.
AB  - It is natural to see conscious perceptions as typically bringing with them a
      degree of confidence about what is perceived. So one might also expect such
      confidence not to occur if a perception is not conscious. This has resulted in
      the use of confidence as a test or measure of consciousness, one that may be more
      reliable and fine-grained than the traditional appeal to subjective report as a
      test for a perception's being conscious. The following describes theoretical
      difficulties for the use of confidence as a reliable test for consciousness,
      which show that confidence is less reliable than subjective report. Difficulties
      are also presented for the use of confidence ratings in assessing degrees of
      consciousness, which cast doubt on any advantage confidence might have from being
      more fine-grained than subjective report. And an explanation is proposed for the
      wide appeal of using confidence to assess subjective awareness, an explanation
      that also makes clear why confidence is less reliable than subjective report.

PMID- 29355647
TI  - Reliability in reporting perceptual experience: Behaviour and electrophysiology
      in hemianopic patients.
AB  - Patients with hemianopia can present with the so called blindsight phenomenon:
      the ability to perform above chance in the absence of acknowledged awareness.
      Proper awareness reports are, thus, crucial to distinguish pure forms of
      blindsight from forms of conscious, yet degraded, vision. It has, in fact, been
      recently shown that 1) dichotomous and graded measures to assess awareness can
      lead to different behavioural results in patients with hemianopia and that 2)
      different grades of perceptual clarity show different electrophysiological
      correlates in healthy participants. Here, in hemianopic patients, we assessed
      awareness by means of the four-point Perceptual Awareness Scale (PAS) and
      investigated its neural correlates with Event Related Potentials (ERPs). Results
      showed that patients, in most of the cases, can rate the clarity of their
      perceptual experience in a graded manner. Moreover, graded perceptual experiences
      correlated with the amplitude of deflections in ERPs. These results call for the
      need to assess perceptual awareness with graded measures and for the importance
      to use electrophysiological data to correlate behaviour with neural processing.

PMID- 29355648
TI  - Impaired awareness of action-outcome contingency and causality during healthy
      ageing and following ventromedial prefrontal cortex lesions.
AB  - Detecting causal relationships between actions and their outcomes is fundamental
      to guiding goal-directed behaviour. The ventromedial prefrontal cortex (vmPFC)
      has been extensively implicated in computing these environmental contingencies,
      via animal lesion models and human neuroimaging. However, whether the vmPFC is
      critical for contingency learning, and whether it can occur without subjective
      awareness of those contingencies, has not been established. To address this, we
      measured response adaption to contingency and subjective awareness of action
      outcome relationships in individuals with vmPFC lesions and healthy elderly
      subjects. We showed that in both vmPFC damage and ageing, successful behavioural
      adaptation to variations in action-outcome contingencies was maintained, but
      subjective awareness of these contingencies was reduced. These results highlight
      two contexts where performance and awareness have been dissociated, and show that
      learning response-outcome contingencies to guide behaviour can occur without
      subjective awareness. Preserved responding in the vmPFC group suggests that this
      region is not critical for computing action-outcome contingencies to guide
      behaviour. In contrast, our findings highlight a critical role for the vmPFC in
      supporting awareness, or metacognitive ability, during learning. We further
      advance the hypothesis that responding to changing environmental contingencies,
      whilst simultaneously maintaining conscious awareness of those statistical
      regularities, is a form of dual-tasking that is impaired in ageing due to reduced
      prefrontal function.

PMID- 29355649
TI  - Diminished choice effect on anticipating improbable rewards.
AB  - Previous research found that the neural substrates underlying perceived control
      highly overlap those of reward system, especially during reward anticipation
      stage. The current event-related potential study examined whether the experience
      of choice by which individuals exercise control is modulated by reward
      probability during reward anticipation stage as indexed by the stimulus-preceding
      negativity (SPN). Thirty participants performed a cued gambling task during which
      choices could be made either by themselves (a choice condition) or by a computer
      (a no-choice condition) with three levels of reward probability (low, medium, and
      high) while their EEG was recording. As expected, the participants perceived
      higher control during the choice compared to no-choice condition.
      Correspondingly, the SPN was enhanced in the choice condition than the no-choice
      condition. Critically, the SPN choice effect was present when reward probability
      was high and medium, but was diminished when reward probability was low. These
      findings suggest that the perceived control as exercised by choice is associated
      with reward anticipation, which may be sensitive to the fundamental properties of
      reward.

PMID- 29355650
TI  - Metabolic response 4 years after gastric bypass in a complete cohort with type 2
      diabetes mellitus.
AB  - AIMS: To evaluate the long-term remission rates of type 2 diabetes mellitus and
      associated comorbidities after gastric bypass surgery in a complete cohort, in a
      real-life clinic setting. METHODS: A retrospective study of all consecutive
      patients with type 2 diabetes mellitus who underwent gastric bypass at a Veterans
      Affairs Medical Center from 2003 to 2010. The main outcome was remission of type
      2 diabetes mellitus defined as HbA1c <6.5% (49 mmol/mol) without diabetic
      medication usage. Secondary outcomes were remission of hypertension and
      hyperlipidemia, weight loss, and long-term complications four years post-gastric
      bypass. RESULTS: Eighty-four patients with type 2 diabetes mellitus underwent
      gastric bypass. Four-year follow-up data were available for 92% (77/84) of
      patients. The patients (73% male; mean age 54 years) had a mean body mass index
      of 49 kg/m2 +/- 8.3. Hypertension and hyperlipidemia prevalence were 92% and 85%,
      respectively. The mean total body weight decrease over four years was 35 kg +/-
      21. Remission of type 2 diabetes mellitus occurred in 15% at 6 months and 49%
      four years after surgery. Diabetes remission was more likely (OR 3.2; 95%
      confidence interval 1.2-9.7) in patients not using insulin at baseline. Remission
      rates were 12% (9/74) for hypertension and 16% (11/68) for hyperlipidemia. Long
      term surgical complications included reoperation (11%), incisional hernia (10%)
      and anastomotic ulcer (10%). Forty-four percent of patients had one or more
      nutritional complications. CONCLUSIONS: The metabolic effects of gastric bypass
      are significant and durable for at least four years, even in a predominantly male
      cohort and real-life clinical setting.

PMID- 29355651
TI  - Direct and indirect health economic impact of hypoglycaemia in a global
      population of patients with insulin-treated diabetes.
AB  - AIMS: The Hypoglycaemia Assessment Tool (HAT) study investigated the health
      economic impact of hypoglycaemic events in 24 countries, including countries
      without previously published data on hypoglycaemia. METHODS: Self-assessment
      questionnaires and patient diaries (4-week prospective period) were completed by
      adults with type 1 (T1D) or type 2 diabetes (T2D) treated with insulin for more
      than 12 months (N = 27,585). RESULTS: Direct economic impacts of hypoglycaemia
      during the 4-week prospective period, included increased blood glucose monitoring
      (reported by 69.7% [T1D] and 60.9% [T2D] of patients), hospitalisation (T1D 2.1%;
      T2D 3.4% of patients) and medical contact (clinic or telephone; T1D 3.8%; T2D
      6.8% of patients). Regional variation in medical contact and hospitalisation was
      found, with the highest usage in Russia (T1D 17.1%; T2D 17.3%), and Latin America
      (T1D 5.2%; T2D 6.8%) respectively. Indirect economic impacts following
      hypoglycaemia included loss of productivity due to absence from work or study;
      3.9% (T1D) and 6.2% (T2D) of patients. Regional differences in work productivity
      were noted among patients with T2D, with a low prevalence in Northern Europe and
      Canada (0.9%) and high in Southeast Asia (14.6%). CONCLUSIONS: This study shows
      that hypoglycaemia has a significant but variable impact on the economics of
      diabetes healthcare globally.

PMID- 29355652
TI  - Liraglutide ameliorates early renal injury by the activation of renal FoxO1 in a
      type 2 diabetic kidney disease rat model.
AB  - AIMS: The aim of this study was to investigate the effects of liraglutide on
      renal injury and the renal expression of FoxO1 in type 2 diabetic rats. METHODS:
      Type 2 diabetic rats model was induced by a high-sugar and high-fat diet and
      intraperitoneal injection of low-dose Streptozotocin (STZ) (30 mg/kg). Five weeks
      after STZ injection, diabetic rats were randomly treated with or without
      subcutaneous injection of liraglutide (0.2 mg/kg/12 h) for eight weeks. Diabetes
      related physical and biochemical indicators, renal histopathological and
      ultrastructural changes, the expression of renal transforming growth factor beta
      1 (TGF-beta1), fibronectin (FN), type IV collagen (Col IV), protein kinase B
      (Akt), forkhead box protein O1 (FoxO1) and manganese superoxide dismutase (MnSOD)
      were measured. RESULTS: Rats in DN group showed a significant increase in fasting
      blood glucose, HbA1c, kidney to body weight index, serum creatinine (Scr), blood
      urea nitrogen (BUN), urinary albumin excretion, mesangial matrix index,
      glomerular basement membrane (GBM) thickening, podocyte foot process fusion, the
      mRNA and protein levels of renal TGF-beta1, FN and Col IV and a dramatic decrease
      in the mRNA and protein levels of renal MnSOD, all of which were significantly
      ameliorated by liraglutide. In addition, liraglutide also increased the
      expression of FoxO1 mRNA and reduced renal phosphorylation levels of Akt and
      FoxO1 protein. CONCLUSIONS: These results suggest that liraglutide may exert a
      renoprotective effect by a FoxO1-mediated upregulation of renal MnSOD expression
      in the early DKD.

PMID- 29355653
TI  - Discovery and validation of serum creatinine variability as novel biomarker for
      predicting onset of albuminuria in Type 2 diabetes mellitus.
AB  - AIM: We aim to study association serum creatinine(cr) variability and albuminuria
      progression. METHODS: We conducted a retrospective cohort study on patients with
      Type 2 Diabetes Mellitus at a Diabetes Centre in Singapore ("discovery cohort").
      Outcome is worsening of urinary albumin-to-creatinine(ACR) across stages. Cr
      variability was expressed as adjusted cr-intrapersonal standard deviation(SD) and
      coefficient-of-variation(cr-CV). A separate cohort was used for validating
      association between cr variability and albuminuria progression ("validation
      cohort"). RESULTS: Over median follow-up of 4.2 years, 38.4% of 636 patients had
      albuminuria progression in the discovery cohort. Increasing log-transformed
      adjusted cr-intrapersonal SD and cr-CV were significantly associated with
      albuminuria progression: HRs 1.43 (95%CI 1.11-1.85) and 1.44 (1.11-1.87)
      respectively in the discovery cohort, and HRs 1.94 (1.09-3.45) and 1.91 (1.05
      3.45) respectively in the validation cohort. When stratified by baseline urinary
      ACR, higher cr variability was significantly associated with albuminuria
      progression in patients with normoalbuminuria but not microalbuminuria.
      CONCLUSIONS: Cr variability independently predicts albuminuria onset. This is
      evident in patients with normoalbuminuria, suggesting that higher cr variability
      could herald albuminuria onset.

PMID- 29355654
TI  - Improving release completeness from PLGA-based implants for the acid-labile model
      protein ovalbumin.
AB  - The objectives of this study were to assess the feasibility of hot melt extrusion
      (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to
      characterize and improve protein release from the implants. Ovalbumin (OVA) was
      stable during extrusion, which was attributed to a protective effect of the
      biodegradable matrix. OVA release was characterized by a low burst, a slow
      release up to day 21, which plateaued thereafter resulting in incomplete release
      for all evaluated protein loadings. Release incompleteness was accompanied by the
      formation of an insoluble residual mass. Further characterization of this mass
      indicated that it consisted of non-covalent protein aggregates and polymer, where
      ovalbumin was ionically bound as the pH inside the degrading matrix decreased
      below the pI of the protein. Although higher protein release was obtained with
      the inclusion of weak bases because of their neutralizing effect, OVA aggregation
      and release incompleteness were not fully avoided. With the use of shellac, a
      well-known enteric and biocompatible polymer, as protective excipient, a distinct
      late release phase occurred and release completeness was increased to more than
      75% cumulative release. Shellac apparently protected the protein against the
      acidic microclimate due to its low solubility at low pH. Protected OVA was thus
      released once the pH increased due to a declining PLGA-oligomer formation. The
      result was a triphasic release profile consisting of an initial burst, a slow
      diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase
      over the next 3 weeks. An acid-labile protein like OVA was thus feasibly
      protected from interactions with PLGA and its degradation products, resulting in
      a controlled delivery of more than 85% of the original payload.

PMID- 29355655
TI  - Process analytical technology in continuous manufacturing of a commercial
      pharmaceutical product.
AB  - The implementation of process analytical technology and continuous manufacturing
      at an FDA approved commercial manufacturing site is described. In this direct
      compaction process the blends produced were monitored with a Near Infrared (NIR)
      spectroscopic calibration model developed with partial least squares (PLS)
      regression. The authors understand that this is the first study where the
      continuous manufacturing (CM) equipment was used as a gravimetric reference
      method for the calibration model. A principal component analysis (PCA) model was
      also developed to identify the powder blend, and determine whether it was similar
      to the calibration blends. An air diagnostic test was developed to assure that
      powder was present within the interface when the NIR spectra were obtained. The
      air diagnostic test as well the PCA and PLS calibration model were integrated
      into an industrial software platform that collects the real time NIR spectra and
      applies the calibration models. The PCA test successfully detected an equipment
      malfunction. Variographic analysis was also performed to estimate the sampling
      analytical errors that affect the results from the NIR spectroscopic method
      during commercial production. The system was used to monitor and control a 28 h
      continuous manufacturing run, where the average drug concentration determined by
      the NIR method was 101.17% of label claim with a standard deviation of 2.17%,
      based on 12,633 spectra collected. The average drug concentration for the tablets
      produced from these blends was 100.86% of label claim with a standard deviation
      of 0.4%, for 500 tablets analyzed by Fourier Transform Near Infrared (FT-NIR)
      transmission spectroscopy. The excellent agreement between the mean drug
      concentration values in the blends and tablets produced provides further evidence
      of the suitability of the validation strategy that was followed.

PMID- 29355656
TI  - 3D printing applications for transdermal drug delivery.
AB  - The role of two and three-dimensional printing as a fabrication technology for
      sophisticated transdermal drug delivery systems is explored in literature. 3D
      printing encompasses a family of distinct technologies that employ a virtual
      model to produce a physical object through numerically controlled apparatuses.
      The applicability of several printing technologies has been researched for the
      direct or indirect printing of microneedle arrays or for the modification of
      their surface through drug-containing coatings. The findings of the respective
      studies are presented. The range of printable materials that are currently used
      or potentially can be employed for 3D printing of transdermal drug delivery (TDD)
      systems is also reviewed. Moreover, the expected impact and challenges of the
      adoption of 3D printing as a manufacturing technique for transdermal drug
      delivery systems, are assessed. Finally, this paper outlines the current
      regulatory framework associated with 3D printed transdermal drug delivery
      systems.

PMID- 29355657
TI  - FBW7 loss promotes epithelial-to-mesenchymal transition in non-small cell lung
      cancer through the stabilization of Snail protein.
AB  - The E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7alpha)
      functions as a putative tumor suppressor in non-small cell lung cancer (NSCLC)
      due to its regulation of a set of oncogenic proteins associated with cell
      proliferation and mitosis. Increasing efforts have been focused on the
      understanding of FBW7 in determining cell cycle progression and apoptosis
      induction, however, the correlation between FBW7 and tumor metastasis is not
      fully understood. In this study, we reported a potential anti-metastatic effect
      of FBW7 in non-small cell lung cancer (NSCLC). In this model, FBW7 inhibited
      cancer cell metastasis primarily by inducing ubiquitination and proteolysis of
      the transcriptional factor Snail, which suppressed E-cadherin cell tight junction
      protein expression. Loss of FBW7 would stabilize the Snail protein, thus, inhibit
      E-cadherin expression and promote metastasis in vitro and in vivo. Moreover,
      Snail ubiquitination and degradation were also achieved by pharmacological
      approach, in which the FBW7 agonist oridonin treatment led to Snail proteolysis.
      Furthermore, FBW7 silencing stabilized Snail protein and induced epithelial-to
      mesenchymal transition (EMT), and acquisition of migration and invasion
      properties in NSCLC. Overall, our study provides new insights into the FBW7-Snail
      axis in regulating cell migration and invasion, and suggests that targeting FBW7
      may be a potent approach to inhibit metastasis in NSCLC.

PMID- 29355658
TI  - Targeting autophagy in gastrointestinal malignancy by using nanomaterials as drug
      delivery systems.
AB  - Autophagy is a conserved catabolic process involving large protein degradation by
      a ubiquitous autophagosomic signaling pathway, which is essential for cellular
      homeostasis. It is triggered by environmental factors such as stress, lack of
      nutrients, inflammation, and eliminating intracellular pathogens. Although the
      mechanisms underlying autophagy are still unclear, increasing evidence
      illuminates the magnitude of autophagy in a wide range of physiological processes
      and human diseases. Simultaneously, research community has focused on the
      triggering of autophagy by the internalization of engineered nanomaterials, which
      indicates a new line of revolution in cancer cure. However, most studies on
      nanoparticle-induced autophagy focus on brain, breast, and cervical cancers;
      limited reports are available on gastrointestinal (GI) cancers. Therefore, the
      aim of this mini review is to discuss in detail the role of autophagy in GI
      malignancy and the status of research on nanoparticle-induced autophagy.

PMID- 29355659
TI  - Sorting nexin 10 acts as a tumor suppressor in tumorigenesis and progression of
      colorectal cancer through regulating chaperone mediated autophagy degradation of
      p21Cip1/WAF1.
AB  - Chaperone-mediated autophagy (CMA) characterized by the selective degradation of
      target proteins has been linked with tumorigenesis in recent years. Here, we
      explored the function of sorting nexin 10 (SNX10), a protein involved in
      maintaining endosome/lysosome homeostasis, in mediating CMA activity and its
      impact on the progression of mouse inflammation-driven colorectal cancer. Our
      results revealed that SNX10 deficiency increased the activation of CMA by
      preventing the degradation of lysosomal LAMP-2A. In SNX10 KO cells, we disclosed
      that p21Cip1/WAF1, a master effector in various tumor suppressor pathways, is a
      substrate of CMA, and decrease of p21Cip1/WAF1 caused by SNX10-mediated CMA
      activation contributes to HCT116 cell proliferation and survival. Moreover, we
      found that SNX10 KO promoted tumorigenesis in the mouse colorectum which could be
      restored by SNX10 over-expression. Furthermore, SNX10 was remarkably down
      regulated in human CRC tissues which showed the increased activity of CMA and
      decreased expression of p21Cip1/WAF1. These findings suggest that SNX10 acts as a
      tumor suppressor in the mouse colorectum and drives inflammation-associated
      colorectal cancer by a chaperone-mediated autophagy mechanism.

PMID- 29355660
TI  - Long non-coding RNAs in glioma progression.
AB  - Glioma is one of most malignant primary tumors of the brain. However, due to a
      lack of effective means for diagnosing and treating glioma, the prognosis of
      glioma patients remains poor. Therefore, understanding the molecular mechanism of
      glioma progression is essential for effective treatment. Long non-coding RNAs
      (lncRNAs) are novel regulators of gene expression at the transcriptional, post
      transcriptional and epigenetic levels. Recent evidence indicates that lncRNAs may
      play important roles in regulating the progression of glioma. In this article, we
      review the expression profile of lncRNAs in glioma and discuss the functions and
      known mechanisms of several representative lncRNAs in detail, as well as the
      prospects of lncRNAs as diagnostic and prognostic biomarkers and therapeutic
      targets.

PMID- 29355661
TI  - Response to Letter to the Editor on our paper "Evaluation of radioisotopic and
      non-radioisotopic versions of local lymph node assays for subcategorization of
      skin sensitizers compliant to UN GHS rev 4" by Ha et al. (Submitted 25 Jun 2017).

PMID- 29355663
TI  - First detection of mcr-1 plasmid-mediated colistin-resistant Escherichia coli in
      Lebanese poultry.

PMID- 29355662
TI  - Biotherapeutics in non-clinical development: Strengthening the interface between
      safety, pharmacokinetics-pharmacodynamics and manufacturing.
AB  - Biological drugs comprise a wide field of different modalities with respect to
      structure, pharmacokinetics and pharmacological function. Considerable non
      clinical experience in the development of proteins (e.g. insulin) and antibodies
      has been accumulated over the past thirty years. In order to improve the efficacy
      and the safety of these biotherapeutics, Fc modifications (e.g. Fc silent
      antibody versions), combinations (antibody-drug conjugates, protein-nanoparticle
      combinations), and new constructs (darpins, fynomers) have been introduced. In
      the last decade, advanced therapy medicinal products (ATMPs) in research and
      development have become a considerable and strongly growing part of the
      biotherapeutic portfolio. ATMPs consisting of gene and cell therapy modalities or
      even combinations of them, further expand the level of complexity, which already
      exists in non-clinical development strategies for biological drugs and has
      thereby led to a further diversification of expertise in safety and PKPD
      assessment of biological drugs. It is the fundamental rationale of the BioSafe
      meetings, held yearly in the EU and in the US, to convene experts on a regular
      basis and foster knowledge exchange and mutual understanding in this fast growing
      area. In order to reflect at least partially the variety of the biotherapeutics
      field, the 2016 EU BioSafe meeting addressed the following topics in six
      sessions: (i) In vitro Meets in vivo to Leverage Biologics Development (ii) New
      developments and regulatory considerations in the cell and gene therapy field
      (iii) CMC Challenges with Biologics development (iv) Minipigs in non-clinical
      safety assessment (v) Opportunities of PKPD Assessment in Less Common
      Administration Routes In the breakout sessions the following questions were
      discussed: (i) Cynomolgus monkey as a reprotoxicology Species: Impact of
      Immunomodulators on Early Pregnancy Maintenance (ii) Safety Risk of Inflammation
      and Autoimmunity Induced by Immunomodulators (iii) Experience with non-GMP
      Material in Pivotal Non-clinical Safety Studies to Support First in Man (FiM)
      Trials (iv) Safety Assessment of Combination Products for Non-oncology.

PMID- 29355664
TI  - Molecular analysis of low-level tetracycline resistance in clinical isolates of
      Helicobacter pylori among dyspeptic patients in South West Nigeria.
AB  - OBJECTIVES: The aim of this study was to determine the occurrence of 16S rRNA
      mutations associated with low-level tetracycline resistance in Helicobacter
      pylori isolates from adult dyspeptic patients in South West Nigeria. METHODS:
      Susceptibility testing to tetracycline of 50 H. pylori isolates was performed by
      Etest. The 535-bp conserved region of the H. pylori tetracycline-binding site of
      16S rRNA was amplified by PCR, followed by sequencing and multiple sequence
      alignment for all 50 clinical isolates. RESULTS: Of the 50 clinical isolates
      examined, DNA sequence analysis revealed nucleotide substitutions in 7 isolates
      at positions 926-928. Of the seven isolates, two demonstrated reduced
      susceptibility to tetracycline with Etest minimum inhibitory concentrations
      (MICs) of 0.75-1.0mg/L, whilst the other five isolates were resistant with MICs
      of 1.5-24mg/L (resistance breakpoint >1mg/L). The two isolates with reduced
      susceptibility had single nucleotide substitution of A926G, whilst the five
      resistant isolates demonstrated double base pair substitutions of G927T/A928C and
      A926G/A928C and a single nucleotide substitution of A926G. CONCLUSIONS: This
      study shows that low-level tetracycline resistance amongst H. pylori-positive
      dyspeptic patients is associated with reduced susceptibility and resistance to
      tetracycline. This is the result of 1-bp and 2-bp differences in positions 926
      and 926-928, respectively, in the 16S rRNA of H. pylori.

PMID- 29355665
TI  - Scientific underpinnings of biotechnology regulatory frameworks.
AB  - Part of what is presently missing at domestic regulatory levels (and that is
      important at the international level as well) is a detailed understanding of what
      the rules of, and for, regulation should be, who the actors, stakeholders and
      major decision makers are and finally, how to get agreement about the rules.
      Greater insights into the system of rules that underpin regulatory frameworks for
      agri-food and biotechnology products in genetically modified (GM) crop- adopting
      nations will provide value by clarifying the evidence used to commercialize these
      technologies. This article examines the public documents available from Canada,
      the United States, the European Union and the Organisation for Economic
      Cooperation and Development regarding the development of regulatory risk
      assessment frameworks for products of biotechnology to determine what science
      grounds these frameworks. The documentation used to provide the initial structure
      to the existing regulatory frameworks identifies the linkages, connections and
      relationships that exist between science, risk assessment and regulatory policy.
      The relationship between risk and regulation has never been more critical to the
      commercialization of innovative agricultural products. Documenting the role of
      science-based risk assessment in regulations and how this has changed over the 20
      years of experience in regulating GM crops will identify changes in the
      risk/regulation relationship.

PMID- 29355666
TI  - The antibody horror show: an introductory guide for the perplexed.
AB  - The biological literature reverberates with the inadequacies of commercial
      research-tool antibodies. The scientific community spends some $2 billion per
      year on such reagents. Excellent accessible scientific platforms exist for
      reliably making, validating and using antibodies, yet the laboratory end-user
      reality is somehow depressing - because they often "don't work". This experience
      is due to a bizarre and variegated spectrum of causes including: inadequately
      identified antibodies; inappropriate user and supplier validation; poor user
      training; and overloaded publishers. Colourful as this may appear, the outcomes
      for the community are uniformly grim, including badly damaged scientific careers,
      wasted public funding, and contaminated literature. As antibodies are amongst the
      most important of everyday reagents in cell biology and biochemistry, I have
      tried here to gently suggest a few possible solutions, including: a move towards
      using recombinant antibodies; obligatory unique identification of antibodies,
      their immunogens, and their producers; centralized international banking of
      standard antibodies and their ligands; routine, accessible open-source
      documentation of user experience with antibodies; and antibody-user
      certification.

PMID- 29355667
TI  - Wound healing in the eye: Therapeutic prospects.
AB  - In order to maintain a smooth optical surface the corneal epithelium has to
      continuously renew itself so as to maintain its function as a barrier to
      fluctuating external surroundings and various environmental insults. After
      trauma, the cornea typically re-epithelializes promptly thereby minimizing the
      risk of infection, opacification or perforation. A persistent epithelial defect
      (PED) is usually referred to as a non-healing epithelial lesion after
      approximately two weeks of treatment with standard therapies to no avail. They
      occur following exposure to toxic agents, mechanical injury, and ocular surface
      infections and are associated with significant clinical morbidity in patients,
      resulting in discomfort or visual loss. In the case of deeper corneal injury and
      corneal pathology the wound healing cascade can also extend to the corneal
      stroma, the layer below the epithelium. Although significant progress has been
      made in recent years, pharmaco-therapeutic agents that promote corneal healing
      remain limited. This article serves as a review of current standard therapies,
      recently introduced alternative therapies gaining in popularity, and a look into
      the newest developments into ocular wound healing.

PMID- 29355668
TI  - Ocular translational science: A review of development steps and paths.
AB  - Developing successful drug delivery methods is challenging for any tissue, and
      the eye is no exception. Translating initial concepts into advanced technologies
      treating diseases in preclinical models and finally into functional and
      marketable products for humans can be particularly daunting. While referring to
      specific ophthalmic companies and products, this review considers key exchanges
      that lead to successful translation. By building on basic science discoveries in
      the academic setting, applied science can perform proof-of-concept work with
      simple, benchtop experiments. Eventually, simple models need to be translated to
      more robust ones where cells, tissues, and entire organisms are incorporated.
      Successful translation also includes performing due diligence of the intellectual
      property, understanding the market needs, undertaking clinical development,
      meeting regulatory requirements, and eventually scale up manufacturing. Different
      stages of the translation can occur in different environments, including moving
      from academia to industry, from one company to another, or between veterinary and
      human applications. The translation process may also rely on contract
      organizations to move through the complex landscape. While the path to a
      commercial, marketable product may not look the same each time, it is important
      to design a development plan with clear goals and milestones to keep on track.

PMID- 29355669
TI  - Clinical applications of the CellSearch platform in cancer patients.
AB  - The CellSearch(r) system (CS) enables standardized enrichment and enumeration of
      circulating tumor cells (CTCs) that are repeatedly assessable via non-invasive
      "liquid biopsy". While the association of CTCs with poor clinical outcome for
      cancer patients has clearly been demonstrated in numerous clinical studies,
      utilizing CTCs for the identification of therapeutic targets, stratification of
      patients for targeted therapies and uncovering mechanisms of resistance is still
      under investigation. Here, we comprehensively review the current benefits and
      drawbacks of clinical CTC analyses for patients with metastatic and non
      metastatic tumors. Furthermore, the review focuses on approaches beyond CTC
      enumeration that aim to uncover therapeutically relevant antigens, genomic
      aberrations, transcriptional profiles and epigenetic alterations of CTCs at a
      single cell level. This characterization of CTCs may shed light on the
      heterogeneity and genomic landscapes of malignant tumors, an understanding of
      which is highly important for the development of new therapeutic strategies.

PMID- 29355670
TI  - Access to dental services for children with intellectual and developmental
      disabilities - A scoping review.
AB  - BACKGROUND: Children with Intellectual and Developmental Disabilities (IDD) face
      considerable challenges in participating in dental services. These challenges
      include resource constraints and inadequate skills of health service providers to
      work with this population. AIM: The aim was to scope published studies that
      addressed access to dental services for children with IDD in order to determine
      the extent to which various barriers have been researched, using an access
      framework derived from the literature. Access was defined to include the six
      dimensions of accessibility, availability, affordability, accommodation,
      acceptability, and appropriateness. METHOD: Arksey and O'Malley's scoping review
      framework was used. Relevant databases (e.g., Medline) were searched for all
      empirical studies conducted from January 2000 to February 2017 that met inclusion
      criteria. Data were extracted along the six dimensions of the access framework.
      RESULTS: Sixteen international studies were identified which indicated common key
      barriers to dental service use: the difficulties of physical inaccessibility,
      lack of access to information among carers, lack of knowledge of disability
      issues, and low experience and skills in caring for children with IDD among
      dental practitioners. CONCLUSIONS: Key recommendations made were exploring dental
      practitioners' understanding of disability legislation and developing training
      for practitioners to expand on issues specific to IDD.

PMID- 29355671
TI  - Reversible inactivation of interpeduncular nucleus impairs memory consolidation
      and retrieval but not learning in rats: A behavioral and molecular study.
AB  - The Interpedundular nucleus (IPN) is a small midbrain structure located deeply
      between the two cerebral peduncles. The strategic placement of this nucleus makes
      it a possible relay between structures involved in the modulation of hippocampal
      theta rhythm activity. In this study we aimed to investigate how reversible
      inactivation of IPN could affect the acquisition, consolidation and retrieval
      phases of memory in passive avoidance (PA) and Morris water maze (MWM) tasks. To
      support our data, molecular studies were performed in order to detect possible
      changes in the expression of proteins related to learning and memory in the
      hippocampus. To address this issue rats' IPN was reversibly inactivated by
      microinjection of lidocaine hydrochloride (4%). After the behavioral studies, the
      phosphorylation of CREB and P70, and c-fos expression levels in the hippocampus
      were determined using western blotting and immunohistochemistry respectively. Our
      results in the PA and MWM tasks showed that IPN reversible inactivation could
      impair immediate post training consolidation and retrieval while it had no effect
      on the acquisition phase. In addition, there was a deficit in the retention of
      the MWM working memory. Our data showed the ratio of pCREB/CREB, pP70/P70 and c
      fos expression in the hippocampus significantly decreased after IPN reversible
      inactivation. Collectively, the results show that behaviorally defined changes
      could be due to what happens molecularly in the hippocampus after IPN reversible
      inactivation. It is concluded that IPN not only makes part of a network involved
      in the modulation of hippocampal theta rhythm activity, but also is actively
      engaged in hippocampal memory formation.

PMID- 29355672
TI  - Assessment of impulsivity in adolescent mice: A new training procedure for a 3
      choice serial reaction time task.
AB  - Immaturity in impulse control among adolescents could result in substance abuse,
      criminal involvement, and suicide. The brains of adolescents and adults are
      anatomically, neurophysiologically, and pharmacologically different. Therefore,
      preclinical models of adolescent impulsivity are required to screen drugs for
      adolescents and elucidate the neural mechanisms underlying age-related
      differences in impulsivity. The conventional 3- or 5-choice serial reaction time
      task, which is a widely used task to assess impulsivity in adult rodents, cannot
      be used for young mice because of two technical problems: impaired growth caused
      by food restriction and the very long training duration. To overcome these
      problems, we altered the conventional training process, optimizing the degree of
      food restriction for young animals and shortening the training duration. We found
      that almost all basal performance levels were similar between the novel and
      conventional procedures. We also confirmed the pharmacological validity of our
      results: the 5-hydroxytryptamine 2C (5-HT2C) receptor agonist Ro60-0175 (0.6
      mg/kg, subcutaneous) reduced the occurrence of premature responses, whereas the 5
      HT2C receptor antagonist SB242084 (0.5 mg/kg intraperitoneal) increased their
      occurrence, consistent with results of previous studies using conventional
      procedures. Furthermore, we detected age-related differences in impulsivity using
      the novel procedure: adolescent mice were found to be more impulsive than adult
      mice, congruent with the results of human studies. Thus, the new procedure
      enables the assessment of impulsivity in adolescent mice and facilitates a better
      understanding of the neurophysiological/pharmacological properties of
      adolescents.

PMID- 29355673
TI  - A role for CA3 in social recognition memory.
AB  - Social recognition memory is crucial for survival across species, underlying the
      need to correctly identify conspecifics, mates and potential enemies. In humans
      the hippocampus is engaged in social and episodic memory, however the circuit
      mechanisms of social memory in rodent models has only recently come under
      scrutiny. Work in mice has established that the dorsal CA2 and ventral CA1
      regions play critical roles, however a more comprehensive comparative analyses of
      the circuits and mechanisms required has not been reported. Here we employ
      conditional genetics to examine the differential contributions of the hippocampal
      subfields to social memory. We find that the deletion of NMDA receptor subunit 1
      gene (NR1), which abolishes NMDA receptor synaptic plasticity, in CA3 pyramidal
      cells led to deficits in social memory; however, mice lacking the same gene in DG
      granule cells performed indistinguishable from controls. Further, we use
      conditional pharmacogenetic inhibition to demonstrate that activity in ventral,
      but not dorsal, CA3 is necessary for the encoding of a social memory. These
      findings demonstrated CA3 pyramidal cell plasticity and transmission contribute
      to the encoding of social stimuli and help further identify the distinct circuits
      underlying the role of the hippocampus in social memory.

PMID- 29355674
TI  - Sex differences in rat decision-making: The confounding role of extraneous feeder
      sampling between trials.
AB  - Although male and female rats appear to perform differently in some tasks, a
      clear picture of sex differences in decision-making has yet to develop. This is
      in part due to significant variability arising from differences in strains and
      tasks. The aim of this study was to characterize the effects of sex on specific
      response elements in a reinforcement learning task so as to help identify
      potential explanations for this variability. We found that the primary difference
      between sexes was the propensity to approach feeders out of the task context.
      This extraneous feeder sampling affects choice on subsequent trials in both sexes
      by promoting a lose-shift response away from the last feeder sampled. Female
      rats, however, were more likely to engage in this extraneous feeder sampling, and
      therefore exhibited a greater rate of this effect. Once trials following
      extraneous sampling were removed, there were no significant sex differences in
      any of the tested measures. These data suggest that feeder approach outside of
      the task context, which is often not recorded, could produce a confound in sex
      based differences of reinforcement sensitivity in some tasks.

PMID- 29355676
TI  - A comparative analysis of human bone marrow-resident and peripheral memory B
      cells.

PMID- 29355677
TI  - Asthma, COPD, and overlap in a national cohort: ACO on a gradient.

PMID- 29355675
TI  - Anxiety-like behavior and neuropeptide receptor expression in male and female
      prairie voles: The effects of stress and social buffering.
AB  - Strong social support can negate negative health outcomes - an effect defined as
      'social buffering'. In the present study, using the socially monogamous prairie
      vole (Microtus ochrogaster), we examined whether the presence of a bonded partner
      during a stressful event can reduce stress responses. Adult, pair-bonded female
      and male voles were assigned into experimental groups that were either handled
      (Control), experienced a 1-h immobilization (IMO) stress alone (IMO-Alone), or
      experienced IMO with their partner (IMO-Partner). Thereafter, subjects were
      tested for anxiety-like behavior, and brain sections were subsequently processed
      for oxytocin receptor (OTR) and vasopressin V1a-type receptor (V1aR) binding. Our
      data indicate that while IMO stress significantly decreased the time that
      subjects spent in the open arms of an elevated plus maze, partner's presence
      prevented this behavioral change - this social buffering on anxiety-like behavior
      was the same for both male and female subjects. Further, IMO stress decreased OTR
      binding in the nucleus accumbens (NAcc), but a partner's presence dampened this
      effect. No effects were found in V1aR binding. These data suggest that the
      neuropeptide- and brain region-specific OTR alterations in the NAcc may be
      involved in both the mediation and social buffering of stress responses. Some sex
      differences in the OTR and V1aR binding were also found in selected brain
      regions, offering new insights into the sexually dimorphic roles of the two
      neuropeptides. Overall, our results suggest a potential preventative approach in
      which the presence of social interactions during a stressor may buffer typical
      negative outcomes.

PMID- 29355678
TI  - T-cell gene therapy for perforin deficiency corrects cytotoxicity defects and
      prevents hemophagocytic lymphohistiocytosis manifestations.
AB  - BACKGROUND: Mutations in the perforin 1 (PRF1) gene account for up to 58% of
      familial hemophagocytic lymphohistiocytosis syndromes. The resulting defects in
      effector cell cytotoxicity lead to hypercytokinemia and hyperactivation with
      inflammation in various organs. OBJECTIVE: We sought to determine whether
      autologous gene-corrected T cells can restore cytotoxic function, reduce disease
      activity, and prevent hemophagocytic lymphohistiocytosis (HLH) symptoms in in
      vivo models. METHODS: We developed a gammaretroviral vector to transduce murine
      CD8 T cells in the Prf-/- mouse model. To verify functional correction of Prf-/-
      CD8 T cells in vivo, we used a lymphocytic choriomeningitis virus (LCMV) epitope
      transfected murine lung carcinoma cell tumor model. Furthermore, we challenged
      gene-corrected and uncorrected mice with LCMV. One patient sample was transduced
      with a PRF1-encoding lentiviral vector to study restoration of cytotoxicity in
      human cells. RESULTS: We demonstrated efficient engraftment and functional
      reconstitution of cytotoxicity after intravenous administration of gene-corrected
      Prf-/- CD8 T cells into Prf-/- mice. In the tumor model infusion of Prf-/- gene
      corrected CD8 T cells eliminated the tumor as efficiently as transplantation of
      wild-type CD8 T cells. Similarly, mice reconstituted with gene-corrected Prf-/-
      CD8 T cells displayed complete protection from the HLH phenotype after infection
      with LCMV. Patients' cells showed correction of cytotoxicity in human CD8 T cells
      after transduction. CONCLUSION: These data demonstrate the potential application
      of T-cell gene therapy in reconstituting cytotoxic function and protection
      against HLH in the setting of perforin deficiency.

PMID- 29355679
TI  - Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid
      asthma.
AB  - BACKGROUND: Dupilumab, an anti-IL-4 receptor alpha mAb, inhibits IL-4/IL-13
      signaling, key drivers of type 2/TH2 immune diseases (eg, atopic/allergic
      disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe
      exacerbations, improved lung function and quality of life, and was generally well
      tolerated in patients with uncontrolled persistent asthma despite using medium-to
      high-dose inhaled corticosteroids plus long-acting beta2-agonists. OBJECTIVE: To
      examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total
      score and its allergic rhinitis (AR)-associated items in asthma patients with
      comorbid perennial allergic rhinitis (PAR). METHODS: A post hoc analysis
      reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w)
      doses under investigation in phase 3 (NCT02414854) was carried out. PAR was
      defined at study entry as a specific response to typical perennial antigens (IgE
      >=0.35 Ku/L). RESULTS: Overall, 241 (61%) patients had PAR. In asthma patients
      with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22
      total score (least squares mean difference, -5.98; 95% CI, -10.45 to -1.51; P =
      .009) and all 4 AR-associated symptoms evaluated (nasal blockage, -0.60; 95% CI, 
      0.96 to -0.25; runny nose, -0.67; 95% CI, -1.04 to -0.31; sneezing, -0.55; 95%
      CI, -0.89 to -0.21; postnasal discharge, -0.49; 95% CI, -0.83 to -0.16; all P <
      .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically
      significant, decreases in SNOT-22 total score (-1.82; 95% CI, -6.46 to 2.83; P =
      .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no
      differences were observed for these measures versus placebo. CONCLUSIONS:
      Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in
      patients with uncontrolled persistent asthma and comorbid PAR.

PMID- 29355680
TI  - Early life risk factors for chronic sinusitis: A longitudinal birth cohort study.
AB  - BACKGROUND: Chronic sinusitis is a commonly diagnosed condition in adults who
      frequently present with late-stage disease and irreversible changes to the sinus
      mucosa. Understanding the natural history of chronic sinusitis is critical in
      developing therapies designed to prevent or slow the progression of disease.
      OBJECTIVE: We sought to determine early life risk factors for adult sinusitis in
      a longitudinal cohort study (Tucson Children's Respiratory Study). METHODS:
      Physician-diagnosed sinusitis was reported at age 6. Adult sinusitis between 22
      and 32 years was defined as self-reported sinusitis plus physician-ordered sinus
      radiologic films. Atopy was assessed by skin prick test. Individuals were grouped
      into 4 phenotypes: no sinusitis (n = 621), transient childhood sinusitis only (n
      = 57), late-onset adult sinusitis only (n = 68), and early onset chronic
      sinusitis (childhood and adult sinusitis, n = 26). RESULTS: Sinusitis was present
      in 10.8% of children and 12.2% of adults. Childhood sinusitis was the strongest
      independent risk factor for adult sinusitis (odds ratio = 4.2; 95% CI: 2.5-7.1; P
      < .0001; n = 772). Early onset chronic sinusitis was associated with increased
      serum IgE levels as early as at 9 months of age, atopy (assessed by skin prick
      test reactivity), childhood eczema and allergic rhinitis, frequent childhood
      colds, maternal asthma, and with increased prevalence of concurrent asthma. No
      association was found between late-onset adult sinusitis and any of the early
      life risk factors studied. CONCLUSIONS: We identified an early onset chronic
      sinusitis phenotype associated with a predisposition to viral infections/colds in
      early life, allergies, and asthma. Elucidation of the molecular mechanisms for
      this phenotype may lead to future therapies to prevent the progression of the
      disease into adult sinusitis.

PMID- 29355681
TI  - Whole exome sequencing identifies a novel mutation (c.333 + 2T > C) of TNNI3K in
      a Chinese family with dilated cardiomyopathy and cardiac conduction disease.
AB  - Dilated Cardiomyopathy (DCM) and cardiac conduction disease (CCD) are two kinds
      if diseases that can induce heart failure, syncope and even sudden cardiac death
      (SCD). DCM patients can experience CCD at the same time. In recent research, some
      disease-causing genes and variants have been identified in patients with DCM and
      CCD, such as Alpha-Actinin-2 and TNNI3 Interacting Kinase (TNNI3K). In this
      study, we employed whole-exome sequencing (WES) to explore the potential
      causative genes in a Chinese family with DCM and CCD. A novel splice site
      mutation (c.333 + 2 T > C) of TNNI3K was identified and co-segregated with the
      affected family members. This novel mutation was also absent in 200 healthy local
      controls and predicted to be disease-causing by Mutationtaster. The splice site
      mutation (c.333 + 2 T > C) may result in a premature stop codon in exon 4 of the
      TNNI3K gene and can induce nonsense-mediated mRNA decay. Real-time qPCR also
      confirmed that the level of TNNI3K mRNA expression was decreased significantly
      compared with the controls, which may lead to myocardial structural disorder and
      arrhythmia. In this study we reported the third novel mutation of TNNI3K in DCM
      and CCD patients which further supported the important role of TNNI3K in heart
      development and expanded the spectrum of TNNI3K mutations. The results may
      contribute to the genetic diagnosis and counseling of families with DCM and CCD.

PMID- 29355683
TI  - Fine-mapping analysis of the MHC region for vitiligo based on a new Han-MHC
      reference panel.
AB  - Vitiligo is an immune-related disease with patchy depigmentation of skin and hair
      caused by selective destruction of melanocytes. In recent decades, many studies
      have shown the association between vitiligo and HLA genes; however, the results
      of Han Chinese are scarce. In this study, we performed a fine-mapping analysis of
      the MHC region in 2818 Han Chinese subjects through a widely used HLA imputation
      method with a newly built large-scale Han-MHC reference panel. Three new four
      digit HLA alleles (HLA-DQB1 * 02:02, HLA-DQA1 * 02:01 and HLA-DPB1 * 17:01) were
      identified to be associated with the risk of vitiligo, and four previously
      reported alleles were confirmed. Further conditional analysis revealed that two
      important variants, HLA-DQbeta1 amino acid position 135 (OR = 1.79, P = 1.87 * 10
      11) and HLA-B amino acid positions 45-46 (OR = 1.44, P = 5.61 * 10-11), conferred
      most of the MHC associations. Three-dimension ribbon models showed that the
      former is located within the beta2 domain of the HLA-DQbeta1 molecule, and the
      latter lies in the alpha1 domain of the HLA-B molecule, while both are involved
      in specific antigen presenting process. Finally, we summarized all significant
      signals in the MHC region to clarify their complex relationships, and 8.60% of
      phenotypic variance could be explained based on all reported variants in Han
      Chinese so far. Our findings highlight the complex genetic architecture of the
      MHC region for vitiligo in Han Chinese population and expand our understanding of
      the roles of HLA coding variants in the etiology of vitiligo.

PMID- 29355682
TI  - Identification of cyp703a3-3 and analysis of regulatory role of CYP703A3 in rice
      anther cuticle and pollen exine development.
AB  - Anther cuticle and pollen exine are two elaborated lipid-soluble barriers
      protecting pollen grains from environmental and biological stresses. However,
      less is known about the mechanisms underlying the synthesis of these lipidic
      polymers. Here, we identified a no-pollen male-sterility mutant cyp703a3-3 from
      the indica restorer line Zhonghui 8015 (Zh8015) mutant library treated with
      60Cogamma-ray radiation. Histological analysis indicated that cyp703a3-3
      underwent abnormal tapetal cells development, produced few orbicules and secreted
      less sporopollenin precursors to anther locule, as well as cutin monomers on
      anther. Genetic analysis revealed that cyp703a3-3 was controlled by a single
      recessive gene. Map-based cloning was performed to narrow down the mutant gene to
      a 47.78-kb interval on the chromosome 8 between two markers S15-29 and S15-30.
      Sequence analysis detected three bases (GAA) deletion in the first exon of
      LOC_Os08g03682, annotated as CYP703A3 with homologous sequences related to male
      sterility in Arabidopsis, causing the Asparagine deletion in the mutant site.
      Moreover, we transformed genomic fragment of CYP703A3 into cyp703a3-3, which male
      sterility phenotype was recovered. Both the wild-type and cyp703a3-3 mutant 3D
      structure of CYP703A3 protein were modeled. Results of qPCR suggested CYP703A3
      mainly expressed in anthers with greatest abundance at microspore stage, and
      genes involved in sporopollenin precursors formation and transportation, such as
      GAMYB, TDR, CYP704B2, DPW2, OsABCG26 and OsABCG15, were significantly reduced in
      cyp703a3-3. Collectively, our results further elaborated CYP703A3 plays vital
      role in anther cuticle and pollen exine development in rice (Oryza sativa L.).

PMID- 29355684
TI  - Impact of adenosine A2a receptor polymorphism rs5751876 on platelet reactivity in
      ticagrelor treated patients.
AB  - Dual antiplatelet therapy constitutes a key point in the management of patients
      with acute coronary syndromes. In particular, ticagrelor, an ADP-antagonist, can
      provide a more potent and predictable platelet inhibition as compared to
      clopidogrel, and adenosine-mediated pathways have been involved in its beneficial
      effects on mortality and myocardial perfusion. However, a quote of patients still
      displays a suboptimal platelet inhibition on ticagrelor, and, while the role of
      genetics in conditioning clopidogrel resistance is well established, few data
      have been reported for ticagrelor. We investigated the impact of rs5751876 C > T
      polymorphism of adenosine A2a receptor (ADORA2a) on platelet reactivity in
      patients during chronic treatment with ticagrelor. We included patients treated
      with ASA and ticagrelor for a recent ACS or elective coronary revascularization.
      Platelet reactivity was assessed at 30-90 days post-discharge by multiple
      electrode aggregometry. HRPR for ticagrelor was defined as ADP-test results >417
      AU*min. Genetic analysis was performed to assess the presence of rs5751876 C > T
      polymorphism of ADORA2a receptor. We included 244 patients in our study, 174
      (71.3%) patients carried the polymorphism (T allele), 51 (20.9%) of them in
      homozygosis (T/T). C-allele carriers (homozygotes C/C and heterozygotes C/T)
      showed no difference in baseline characteristics but for lower HDL-cholesterol (p
      = 0.01). An absolute lower rate of HRPR on ticagrelor was observed in homozygotes
      T/T (p = 0.03). At multivariate analysis, C allele carriage was independently
      associated with the rate of HRPR on ticagrelor (adjusted OR[95%CI] = 4.63[1.02
      21.01], p = 0.048). Our study results showed a significant independent
      association between rs5751876 allele C carriage and a higher rate of high
      residual platelet reactivity in patients on ticagrelor after a recent ACS or PCI.

PMID- 29355685
TI  - Development and characterisation of chondroitin sulfate- and hyaluronic acid
      incorporated sorbitan ester nanoparticles as gene delivery systems.
AB  - Glycosaminoglycans (GAGs) are natural polymers that are broadly used in gene
      delivery systems to increase stability as well as decrease toxicity and
      nonspecific interactions, thereby increasing transfection efficiency. In this
      work, we propose sorbitan ester-based lipid nanoparticles (SENS) functionalised
      with the GAGs chondroitin sulfate (CS) and hyaluronic acid (HA) as gene delivery
      systems. For this purpose, we describe the design and evaluation of these
      nanosystems loaded with plasmid DNA, including an evaluation of their
      physicochemical characteristics, stability properties, ability to protect and
      efficiently transfect cells with Enhanced Green Fluorescent Protein plasmid
      (pEGFP) in vitro, and biocompatibility both in vitro and in vivo. We confirm that
      molecules with high biological value and targeting potential, such as HA and CS,
      can be successfully incorporated into our recently developed sorbitan ester-based
      nanoparticles (SENS) and that this incorporation leads to effective stabilisation
      of both nanosystems as well as protects plasmid DNA. We demonstrated that the
      aforementioned incorporation of HA and CS enables long-term stability of the
      nanosystems in both liquid and lyophilised states, which is a remarkable property
      that can aid in their transfer to industry. The ability of these functionalised
      nanosystems to transfect the A549 cell line without compromising cell viability
      was also shown, as well as their innocuous safety profile in vivo. Thus, we
      provide valuable evidence of the suitable properties and potential of these
      hybrid nanoparticles as gene delivery systems.

PMID- 29355686
TI  - Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach
      for the treatment of ovarian cancer.
AB  - We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding
      inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT).
      Tetrabutyl ammonium salt of Mo6Br14 cluster unit, (TBA)2Mo6Br14, presents
      promising photosensitization activity in the destruction of targeted cancer
      cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent
      displacement method showing spherical shapes, zeta potential values around -30
      mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC
      analysis revealed the lack of strong chemical interaction between the cluster and
      the polymer within the nanoparticles. In vitro release study showed that
      (TBA)2Mo6Br14 was totally dissolved in 20 min, while CNPs were able to control
      the release of encapsulated cluster. In vitro cellular viability studies
      conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or
      CNPs did not show any sign of toxicity in concentrations up to 20 ug/ml. This
      concentration was selected for photo-activation test on A2780 cells and CNPs were
      able to generate oxygen singlet resulting in a decrease of the cellular viability
      up to 50%, respectively compared to non-activated conditions. This work presents
      (TBA)2Mo6Br14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles
      as an efficient delivery system intended for tumor targeting.

PMID- 29355687
TI  - Key acceptability attributes of orodispersible films.
AB  - The features rendering orodispersible films (ODFs) patient-centric formulations
      are widely discussed in the scientific literature. However there is a lack of
      research studies exploring ODF characteristics with a potential impact on end
      user acceptability. The aim of this study was to identify the key ODF
      characteristics affecting end-user acceptability by developing in vitro test
      methods for the prediction of ODFs acceptability and correlate these formulation
      characteristics with the data obtained from a human panel study. Four drug-free
      single-polymer films were prepared by solvent casting. Solutions of poly(vinyl)
      alcohol (PVOH) 39 KDa (P1), PVOH 197 KDa (P2), carboxymethylcellulose (CMC) 395
      KDa (C1), and CMC 725 KDa (C2) were prepared. Texture analysis and Dynamic
      Mechanical Analysis (DMA) were used to assess film tack. Petri dish and drop
      methods were used to assess disintegration time. A human panel of 24 healthy
      young adults was employed to identify end-user acceptability criteria of the four
      study film samples. Texture analysis data of ODF tack were not found to be in
      agreement with the in vivo perceived stickiness in the mouth. However,
      measurement of the area under the adhesive force curve obtained by DMA correlated
      with in vivo perceived stickiness data for all samples. The disintegration times
      obtained by drop method were more comparable to human panel data than the petri
      dish method. Hence DMA and drop methods proved to be promising methodologies for
      the prediction of the end-user acceptability. The type and molecular weight of
      the film-forming polymer had a strong influence on stickiness perception, whereas
      only polymeric molecular weight influenced perceived disintegration time. The
      human panel study showed that Participant Reported Outcomes (PROs) for the
      perceived stickiness in the mouth and disintegration time of test films received
      significantly different scores between samples, and thus were identified as the
      key attributes with the potential to affect the end-user acceptability. ODF
      stickiness and disintegration time should therefore be evaluated at an early
      stage of the drug product design.

PMID- 29355688
TI  - Metabolomics profiling of steatosis progression in HepaRG(r) cells using sodium
      valproate.
AB  - Non-alcoholic Fatty Liver Disease (NAFLD) is a frequently encountered Drug
      Induced Liver Injury (DILI). Although this stage of the disease is reversible, it
      can lead to irreversible damage provoked by non-alcoholic steatohepatitis (NASH),
      fibrosis and cirrhosis. Therefore, the assessment of NAFLD is a paramount
      objective in toxicological screenings of new drug candidates. In this study, a
      metabolomic fingerprint of NAFLD induced in HepaRG(r) cells at four dosing
      schemes by a reference toxicant, sodium valproate (NaVPA), was obtained using
      liquid-liquid extraction followed by liquid chromatography and accurate mass-mass
      spectrometry (LC-AM/MS). The combination of a strict design of experiment with a
      robust detection method, applied on sodium valproate, validated the possibilities
      of untargeted metabolomics in hepatic toxicological research. Distinctive
      patterns between exposed and control cells were consistently observed,
      multivariate analyses selected up to 200 features of interest, revealing hallmark
      NAFLD-biomarkers, such as diacylglycerol and triglyceride accumulation and
      carnitine deficiency. Initial toxic responses show increased levels of S
      adenosylmethionine and mono-acetylspermidine in combination with only a moderate
      increase in triglycerides. New specific markers of toxicity have been observed,
      such as spermidines, creatine, and acetylcholine. The described design of
      experiment provides a valuable metabolomics platform for mechanistic research of
      toxicological hazards and identified new markers for steatotic progression.

PMID- 29355689
TI  - miR-21-5p as a potential biomarker of inflammatory infiltration in the heart upon
      acute drug-induced cardiac injury in rats.
AB  - Investigation of genomic changes in cardiotoxicity can provide novel biomarkers
      and insights into molecular mechanisms of drug-induced cardiac injury (DICI). The
      main objective of this study was to identify and characterize dysregulated
      microRNAs (miRNAs) in the heart associated with cardiotoxicity. Wistar rats were
      dosed once with either isoproterenol (1.5 mg/kg, i.p), allylamine (100 mg/kg,
      p.o.) or the respective vehicle controls. Heart tissue was collected at 24 h, 48
      h and 72 h post-drug administration and used for histopathological assessment,
      miRNA profiling, immunohistochemical analysis and in situ hybridization.
      Multiplex analysis of 68 miRNAs in the heart revealed a significant upregulation
      of several miRNAs (miR-19a-3p, miR-142-3p, miR-155-5p, miR-208b-3p, miR-21-5p)
      after isoproterenol and one miRNA (miR-21-5p) after allylamine administration.
      Localization of miR-21-5p was specific to inflammatory cell infiltrates in the
      heart after both treatments. Immunohistochemical analysis of Stat3, a known miR
      21-5p regulator, also confirmed its upregulation in cardiomyocytes and
      inflammatory cell infiltrates. The toxicity signatures based on miRNA networks,
      identified in vivo, can potentially be used as mechanistic biomarkers as well as
      to study cardiotoxicity in vitro in order to develop sensitive tools for early
      hazard identification and risk assessment.

PMID- 29355690
TI  - Effect of subchronic exposure to inorganic arsenic on the structure and function
      of the intestinal epithelium.
AB  - Inorganic arsenic (As), the most toxic form of As found in water and food, is
      considered a human carcinogen. Numerous studies show its systemic toxicity,
      describing pathologies associated with chronic exposure. The main pathway of
      exposure to inorganic As is oral, but many of the events that occur during its
      passage through the gastrointestinal tract are unknown. This study evaluates the
      effect of subchronic exposure to inorganic As [As(III): 0.025-0.1 mg/L; As(V):
      0.25-1 mg/L, up to 21 days] on the intestinal epithelium, using Caco-2 cells as
      in vitro model. Inorganic As produces a pro-inflammatory response throughout the
      exposure time, with an increase in IL-8 release (up to 488%). It also causes
      changes in the program of cell proliferation and differentiation, which leads to
      impairment of the cell repair process. In addition, subchronic exposure affects
      the epithelial structure, causing loss of microvilli, fundamental structures in
      the processes of intestinal absorption and digestion. Moreover, the exposure
      affects the epithelial barrier function, evidenced by an increase of Lucifer
      Yellow transport (103-199%). Therefore, it can be concluded that subchronic
      exposure to inorganic As can alter intestinal homeostasis, affecting the mucosal
      layer, which performs the most important functions of the intestinal wall.

PMID- 29355691
TI  - Civilian exposure to chlorine gas: A systematic review.
AB  - INTRODUCTION: Halogen pulmonary irritants (HPIs) are volatile liquids that
      directly damage the respiratory mucosa. Chlorine is readily available in large
      volumes as an industrial chemical and has a significant potential for accidental
      or deliberate release. We conducted a systematic review to determine the clinical
      features; treatment and long-term sequelae of civilian chlorine gas exposure.
      METHODS: A systematic review was conducted using the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Medline; Ovid and
      Google Scholar databases were searched from 1966 to January 2017. A database of
      relevant papers was compiled and descriptive statistics used to summarise the
      data. RESULTS: Thirty-six papers describing 37 incidents involving 1566
      individual acute exposers to chlorine gas were identified. The most common
      reported features were cough (29%), dyspnoea (22%), sore throat (16%), eye
      features (12%) and excessive sputum or haemoptysis (7%). Acute management
      included high-flow oxygen (32.8%); steroids (28.4%); bronchodilators (28.2%) and
      ventilation (2.3%). Nine deaths (0.6%) were reported. Follow-up data available in
      60% of cases; full recovery was reported in 90% of cases where data was
      available. DISCUSSION: Acute chlorine gas exposure in civilian incidents
      presented with acute respiratory features and irritation of the eyes and throat.
      The development of pulmonary oedema or ARDS was relatively rare when compared to
      military experience in the First World War.

PMID- 29355692
TI  - Pregabalin induces conditioned place preference in the rat during the early, but
      not late, stage of neuropathic pain.
AB  - The present study aimed to examine the rewarding effects of pain relief during
      the early and late stages of neuropathic pain using a conditioned place
      preference (CPP) test. Animal models of neuropathic pain were prepared by spinal
      nerve ligation in male Sprague-Dawley rats. Intraperitoneal and intrathecal
      injections of pregabalin (300 mg/kg and 100 MUg/10 MUL, respectively) suppressed
      allodynia in the von Frey test both 2 weeks (early stage) and 4 weeks (late
      stage) after nerve injury. Intraperitoneal and intrathecal injections of
      pregabalin induced CPP during the early stage of neuropathic pain, suggesting
      that the CPP test serves as an objective and quantifiable behavioral assay to
      assess the emotional aspect of pain relief. In contrast with the early stage of
      neuropathic pain, intraperitoneal or intrathecal injection of pregabalin did not
      induce CPP during the late stage of neuropathic pain. The extinguishment of the
      rewarding effects of pregabalin during the late stage of neuropathic pain is
      likely due to dysfunction of the mesolimbic reward system, although the
      possibility that neuronal mechanisms other than dysfunction of the mesolimbic
      reward system are involved in the extinguishment of pregabalin-induced CPP cannot
      be excluded. We previously reported that not only the dopamine release in the
      nucleus accumbens induced by intrathecal pregabalin injection but also that
      induced by sucrose intake were extinguished during the late stage of neuropathic
      pain. These findings, combined with the results of this study, suggest that pain
      chronification leads to dysfunction of the mesolimbic reward system.

PMID- 29355694
TI  - Mechanical ventilation modulates pro-inflammatory cytokine expression in spinal
      cord tissue after injury in rats.
AB  - RATIONALE: Spinal cord injury (SCI) may induce significant respiratory muscle
      weakness and paralysis, which in turn may cause a patient to require ventilator
      support. Central nervous system alterations can also exacerbate local
      inflammatory responses with immune cell infiltration leading to additional risk
      of inflammation at the injury site. Although mechanical ventilation is the
      traditional treatment for respiratory insufficiency, evidence has shown that it
      may directly affect distant organs through systemic inflammation. OBJECTIVES:
      This study aimed to better understand the impact of invasive mechanical
      ventilation on local spinal cord inflammatory responses following cervical or
      thoracic SCI. METHODS: Five groups of female Sprague-Dawley rats were
      anesthetised for 24 h. Three groups received mechanical ventilation: seven rats
      without SCI, seven rats with cervical injury (C4-C5), and seven rats with
      thoracic injury (T10); whereas, two groups were non-ventilated: six rats without
      SCI; and six rats with thoracic injury (T10). Changes in inflammatory responses
      were determined in the spinal cord tissues collected at the local site of injury.
      Cytokines were measured using ELISA. MAIN RESULTS: SCI induced local pro
      inflammatory cytokine IL-6 expression for all groups. Mechanical ventilation also
      had effects on pro-inflammatory cytokines and independently increased TNF-alpha
      and decreased IL-1beta levels in the spinal cords of anesthetized rats.
      CONCLUSION: These data provide the first evidence that mechanical ventilation
      contributes to local inflammation after SCI and in the absence of direct tissue
      injury.

PMID- 29355693
TI  - Genetic deletion of NMDA receptors suppresses GABAergic synaptic transmission in
      two distinct types of central neurons.
AB  - NMDA-type ionotropic glutamate receptors (NMDARs) play an important role in the
      regulation of synapse development and function in the brain. Recently we have
      shown that NMDARs are critical for GABAergic synapse development in developing
      hippocampal neurons. However, it remains unclear whether NMDARs are important for
      establishment of GABAergic synaptic transmission in other types of neurons in the
      brain. Here we report that in both cortical pyramidal neurons and midbrain
      dopamine neurons in ventral tegmental area (VTA), genetic deletion of the GluN1
      subunit, which is required for assembly of functional NMDARs, leads to a strong
      reduction of GABAergic synaptic transmission. These data demonstrate that NMDARs
      play an important role in the development of GABAergic synaptic transmission in
      two types of neurons with distinct developmental origins, and suggest that NMDARs
      are commonly involved in development of GABAergic synaptic transmission in
      different types of neurons in the brain.

PMID- 29355695
TI  - Behavioral effects of the combined use of alcohol and energy drinks on alcohol
      hangover in an experimental mice model.
AB  - In last few years it has been a significant increase in the consumption of
      alcohol combined with energy drink. The aim of this work was to study the effect
      of this mixture in motor and affective behaviors during an alcohol hangover
      episode. Male Swiss mice received one of the following treatments: saline +
      sucrose; saline + energy drink; ethanol + sucrose; ethanol + energy drink.
      Ethanol dose was 3.8 g/kg BW (i.p.) and energy drink dose was 18 ml/kg BW
      (gavage) at ZT1 (8 am) (ZT: Zeitgeber time; ZT0: 7 am; lights on). The behavioral
      tests used were tight rope test to determine motor coordination; hanging wire
      test to study muscular strength; elevated plus maze and open field tests to
      evaluate anxiety like-behavior and locomotor activity. Tests were carried out at
      basal point that matched with lights onset and every 6 h up to 18 h after
      treatments. Hangover onset was established at ZT7 when blood alcohol
      concentration (BAC) was almost zero. Our results showed that the mixture of
      alcohol and energy drink altered significantly motor skills. Specifically, a
      significant decrease was observed in the performance of the animals in the
      tightrope and hanging wire tests in groups treated with the mixture of alcohol
      and energy drink. A significant impairment in the anxiety-like behavior was
      observed mainly at the beginning of alcohol hangover. These findings suggest that
      energy drink added to alcohol extends motor disabilities observed during an
      alcohol hangover episode in comparison with animals that received alcohol alone.

PMID- 29355696
TI  - Effects of non-purified and semi-purified commercial diets on behaviors, plasma
      corticosterone levels, and cecum microbiome in C57BL/6J mice.
AB  - Diverse commercially available feeds are used in animal studies according to the
      purpose of the studies. We sought to understand the relationship between feed
      ingredients and their effects on animal physiology and behaviors. Here, we
      investigated how male laboratory mice (C57BL/6J ("B6") mice) were affected by
      chronic feeding with two commercially available diets, a non-purified diet (MF)
      and a semi-purified diet (AIN-93G). In B6 mice, both diets similarly induced
      spontaneous activities in the home cage and the open field box, anxiety in the
      elevated plus maze test, and depressive-like behaviors in tail-suspension and
      forced-swimming tests, and with both diets, similar data were obtained on calorie
      intake, water intake, body weight gain, and plasma corticosterone levels. By
      contrast, liver weight was significantly higher in MF-fed B6 mice than in AIN-93G
      fed B6 mice. Furthermore, the cecum microbiome was drastically affected by the
      diets, and, specifically, Allobaculum was the major genus (43.4%) in the cecum
      microbiota of AIN-93G-fed mice but its abundance was reduced (to 3.8%) in the
      case of MF-fed mice. Future studies should address whether the differences in
      diet purity and cecum microbiota influence brain functions and behaviors in B6
      mice.

PMID- 29355698
TI  - Comorbidity and cardiac arrest: A continuing conundrum.

PMID- 29355697
TI  - Anti-nociceptive effects of bupivacaine-encapsulated PLGA nanoparticles applied
      to the compressed dorsal root ganglion in mice.
AB  - Bupivacaine is a commonly used local anesthetic in postoperative pain management.
      We evaluated the effects of a prolonged, local delivery of bupivacaine on pain
      behavior accompanying a chronic compression of the dorsal root ganglion (CCD) -
      an animal model of radicular pain. Poly(lactide-coglycolide) (PLGA) nanoparticles
      encapsulating bupivacaine were injected unilaterally into the L3 and L4 DRGs of
      mice just before producing CCD by implanting a stainless-steel rod in the
      intervertebral foramen of each ganglion. Behavioral sensitivity to punctate
      mechanical stimuli (Von Frey filaments) of different forces of indentation,
      delivered to each hind paw, was measured before and on subsequent days of testing
      after the CCD. Nanoparticles were spherical in morphology and 150 +/- 10 nm in
      diameter. Bupivacaine was steadily released as measured in vitro over 35 days. A
      dye that was encapsulated in the nanoparticles was found in the intact DRG after
      2 weeks. CCD alone or with injection of blank (control) nanoparticles produced a
      behavioral hypersensitivity to the punctate stimuli on the ipsilateral paw
      without affecting sensitivity on the contralateral, over a period of 7-14 days.
      The hypersensitivity was manifested as an increased incidence of paw-withdrawal
      to indentation forces normally below threshold (allodynia) and an increased
      shaking to a filament force that always elicited withdrawal prior to CCD
      (hyperalgesia). In contrast, nanoparticles with bupivacaine prevented any
      manifestation of allodynia or hyperalgesia on the ipsilateral hind paw while
      leaving normal nociceptive responses largely intact on both hind paws. CCD
      induced behavioral hypersensitivity to nociceptive stimuli is known to be
      associated with a hyperexcitability of sensory neurons originating in the
      compressed ganglion. We hypothesize that bupivacaine-loaded PLGA nanoparticles
      may prevent the occurrence of this neuronal hyperexcitability without reducing
      the nociceptive information normally conducted from the periphery to the central
      nervous system. The slow, sustained delivery of bupivacaine by nanoparticles may
      provide a means of preventing the occurrence of postoperative neuronal
      hyperexcitability that could develop into chronic neuropathic pain.

PMID- 29355699
TI  - Safety hazards in bacteriocinogenic Staphylococcus strains isolated from goat and
      sheep milk.
AB  - In this study, 28 bacteriocinogenic Staphylococcus strains isolated from goat and
      sheep milk were subjected to the PCR detection of enterotoxin genes (sea-see),
      enterotoxin-like toxin Q gene (selq), toxic shock syndrome toxin gene (tst1), and
      antibiotic resistance genes. They were also evaluated for phenotypic resistance
      against 10 antibiotics and hemolytic activity. The tyramine and histamine
      production was investigated using the agar plate assay and capillary zone
      electrophoretic analysis (CZE). Twenty-five isolates harbored at least one
      enterotoxin gene. The gene sec was the most frequent (89%). The gene tst1 was
      found in 84% of sec-positive isolates. The occurrence of antibiotic resistance
      genes was in the order of blaZ/tetK (100%), mecA/ermB (86%), ermC (50%), and tetM
      (18%). The genes ermA, aac(6')Ie-aph(2")Ia, vanA, and vanB were absent in all the
      isolates. Nineteen isolates were phenotypically susceptible to all the
      antibiotics. The only isolate with phenotypic resistance to penicillin G and
      oxacillin was S. epidermidis 4S93 which had a different SmaI-PFGE profile from
      those of the other S. epidermidis strains. All the S. haemolyticus and S.
      pseudintermedius isolates were not susceptible to trimethoprim. Twenty-five
      isolates showed complete or partial hemolytic activity. None of the isolates was
      able to decarboxylate tyrosine, while CZE analysis revealed histamine formation
      activity in S. haemolyticus 4S12. The occurrence of safety risks in the isolates
      reinforces the need for regular monitoring of food-producing animals to mitigate
      the risks of multidrug resistant and zoonotic pathogens. Moreover, none of the
      isolates fulfilled the safety criteria to be used as starter cultures or
      biopreservatives.

PMID- 29355700
TI  - Characteristics of an Aeromonas trota strain isolated from cerebrospinal fluid.
AB  - Aeromonas are ubiquitous in aquatic habitats. However some species can cause
      infections in humans, but rarely meningitis. Here we describe the isolation and
      characterization of an Aeromonas strain from cerebrospinal fluid of a meningitis
      patient. The isolate, identified as A. trota by biochemical and molecular
      methods, was susceptible to ampicillin but resistant to cephalothin and
      cefazolin. Genome sequencing revealed virulence factor genes such as type VI
      secretion system, aerolysin and lateral flagella. The isolate exhibited swarming
      motility, hemolytic activity and adhesion and cytotoxicity on HeLa cells. This is
      the first report of A. trota associated with meningitis and its virulence
      characteristics.

PMID- 29355701
TI  - Helicobacter pylori infection increases sirt2 gene expression in gastric
      epithelial cells of gastritis patients.
AB  - BACKGROUND: Helicobacter pylori Infection causes some clinical features of the
      human stomach such as gastritis, duodenal ulcer, and gastric cancer. It has been
      shown that Helicobacter pylori infection increases proinflammatory cytokine gene
      expressions in Gastric Epithelial Cells by activation of NF-kB signaling. Sirt1
      and sirt2 as deacetylases play a certain role in the progress of inflammation in
      arthritis and lung infection by impacting the NF-kB. AIMS: Sirt1 and sirt2 gene
      expressions in Gastric Epithelial cells of gastritis patients were surveyed with
      and without Helicobacter pylori infection and rate of prevalence of cagA and hopQ
      genes in Helicobacter pylori strains were investigated. METHODS: 25 biopsy
      samples of gastritis patients with Helicobacter pylori infection and 25 biopsy
      samples of gastritis patients without Helicobacter pylori infection were
      collected from Tohid Hospital in the city of Sanandaj throughout the year 2016.
      CDNA was made from total RNA extracted from biopsy samples (Qiagen(r) Kit). Sirt1
      and sirt2 gene expressions were determined using the Corbett machine (Rotor-Gene
      6000 Software). CagA and hopQ genes of Helicobacter pylori strains were
      determined by PCR using specific primers. RESULTS: The sirt2 gene expression was
      increased in Gastric Epithelial Cells of gastritis patients with Helicobacter
      pylori infection. No significant relationship was found between sirt1 and sirt2
      gene expressions as well as cagA and hopQ as Helicobacter pylori virulence genes.
      CONCLUSIONS: This study shows the Helicobacter pylori infection duo to sirt2 gene
      up-expression. There is not a statistically significance relationship between
      cagA and hopQ Helicobacter pylori genotypes and sirt2 gene up-expression in
      Gastric Epithelial Cells of gastritis patients.

PMID- 29355702
TI  - The fight for invincibility: Environmental stress response mechanisms and
      Aeromonas hydrophila.
AB  - Aeromonas hydrophila is a freshwater-dwelling zoonotic bacterium that has
      economic importance in aquaculture. In the past decade, Aeromonas hydrophila has
      become increasingly important because of its emergence as a food-borne zoonotic
      pathogen that is resistant to different treatment regimes. Being an aquatic
      bacterium, Aeromonas hydrophila is frequently subjected to several stressful
      environmental conditions, including changes in temperature, acidic pH and
      starvation that challenge its survival. To cope with these stressful conditions,
      like every cell, A. hydrophila possesses stress response mechanisms, such as
      alternative sigma factors, two-component systems, heat shock proteins, cold shock
      proteins, and acid tolerance response systems that eventually lead the fittest to
      survive. Moreover, the establishment of genetic variations among the strains
      related to environmental stress is also of great concern. This review presents
      the understandings based on inter-strain variations and stress response behavior
      of A. hydrophila that are important to control the increasing outbreaks of this
      bacterium in both human populations and aquaculture.

PMID- 29355703
TI  - Genetic influence on splenic natural killer cell frequencies and maturation among
      aged mice.
AB  - Natural killer (NK) cells are cytotoxic innate lymphocytes that are integral to
      host defenses against viruses and neoplastic cells. Aging causes phenotypic and
      functional impairment of NK cells, which diminishes innate immune surveillance,
      yet the factors that determine the aged NK cell phenotype have not been
      completely defined. For instance, the genetic basis of the aged NK cell phenotype
      has not been established, but if determined, could highlight important genetic
      regulators of NK cells later in life. In this study, we estimated the
      heritability of splenic NK cell frequencies in aged mice from 15 classical and
      four wild-derived inbred strains. Our data suggest that frequencies of total
      (NKp46+CD3-) NK and mature (NKp46+CD3-CD11b+CD27-) NK cells were highly heritable
      at old age, and that total NK cell frequencies were independent predictors of
      median strain life spans. Strains with divergent phenotypes were compared to
      young-adult controls, and trends of age-related NK cell phenotypic alterations
      were confirmed. Finally, in silico mapping techniques revealed candidate genes
      associated with the aged NK cell phenotype. To our knowledge, these results are
      the first to demonstrate the genetic basis of the aged NK cell phenotype and will
      inform future mechanistic studies of NK cell dysfunction during aging.

PMID- 29355704
TI  - WITHDRAWN: Regular exercise protects aging Drosophila from high-fat-diet-induced
      locomotor impairment, cardiac dysfunction, lifespan shortening, and Nmnat and
      dSir2 expression decline.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29355705
TI  - A brief history of modern aging research.
AB  - Over the last few decades, aging research has emerged as a vibrant area of
      rigorous scientific study. With its humble beginnings in yeast and worms, the
      field has progressed so dramatically that scientists are now able to extend the
      lifespan of mice with the use of small molecule drugs. However, it was not too
      long ago that answering the more basic question, whether aging was amenable to
      scientific study, was itself a topic of contentious debate. To begin to
      understand how a field that was initially thought of as pseudoscience has come so
      far, it is instructive to understand its roots in both theory and practice.

PMID- 29355706
TI  - Blood flow restriction: Methods matter.

PMID- 29355707
TI  - Medicinal plants of northern Angola and their anti-inflammatory properties.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: 32 plants, from which 30 are used in local
      traditional medicine - identified by interviews with the resident population - in
      the province of Uige in northern Angola for the treatment of inflammation related
      disorders, were screened on different anti-inflammatory parameters. Three
      extracts were selected for a detailed ethnobotanical, pharmacological and
      phytochemical investigation based on their in vitro activity. AIM OF THE STUDY:
      We aimed to assess the in vitro anti-inflammatory activity of these plants and
      highlight the active principles of the three most promising candidates. MATERIALS
      AND METHODS: Plant material was collected in northern Angola during eight field
      trips from 2013 to 2015 based on data documented in 61 interviews with 142 local
      informants. 36 methanol (MeOH) extracts were prepared and tested at different
      concentrations (100, 50, 10ug/mL) to evaluate their inhibition on cyclooxygenase
      (COX)-2 expression and on nitric oxide (NO) release in lipopolysaccharide (LPS)
      stimulated J774A.1 macrophages. Five selected extracts were additionally tested
      at the lower concentrations of 5, 2.5, and 1.25ug/mL and for their potential on
      inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6)
      release. The major compounds of three of those five extracts were either
      identified by HPLC coupled with (tandem) mass spectrometry and comparison with
      data from literature or isolated from the respective extracts and confirmed by
      NMR experiments (one and two dimensional). RESULTS: 30 plant species with in
      total 161 citations were mentioned by the informants to have anti-inflammatory
      properties. The predominantly used plant part is the leaf (39%), followed by
      underground organs like roots and rhizomes (25%), bark (18%) as well as fruits
      and seeds with 15%. With 47%, decoction is the most frequent preparation form. A
      large number of the MeOH extracts showed promising activities in our preliminary
      screening for the inhibition of COX-2 expression and NO release. Five extracts
      with high activities in both assays showed also concentration dependent
      inhibition at lower concentrations and a decreased release of two additional pro
      inflammatory mediators (IL-6 and TNF-alpha) vs. LPS. Three leaf extracts where
      chosen for a detailed investigation, which lead to the identification of several
      constituents: verbascoside and isoverbascoside (Acanthus montanus), geraniin,
      chebulagic acid and a large flavonoid fraction (Alchornea cordifolia) as well as
      the four flavonoids astilbin, isovitexin, isoorientin and swertisin (Chaetocarpus
      africanus). Their implication in the observed biological activity was proved by
      comparison with published data of these compounds in identical or similar
      pharmacological models. CONCLUSIONS: The indigenous use of these plants against
      inflammation related ailments could be - at least partly - verified by our in
      vitro models for many of the investigated extracts. Acanthus montanus and
      Alchornea cordifolia particularly stood out with their high activity in all four
      performed assays, which was in accordance with pharmacological studies of their
      major constituents in literature. In addition, this study was the first
      phytochemical investigation of Chaetocarpus africanus and first description of
      the occurrence of the ellagitannins geraniin and chebulagic acid in Alchornea
      cordifolia. These results support the traditional use and should encourage
      further investigations of medicinal plants of northern Angola.

PMID- 29355708
TI  - Juvenile hormone and sesquiterpenoids in arthropods: Biosynthesis, signaling, and
      role of MicroRNA.
AB  - Arthropod molting and reproduction are precisely controlled by the levels of
      sesquiterpenoids, a class of C15 hormones derived from three isoprene units. The
      two major functional arthropod sesquiterpenoids are juvenile hormone (JH) and
      methyl farnesoate (MF). In hemimetabolous insects (such as the aphids, bugs, and
      cockroaches) and holometabolous insects (such as beetles, bees, butterflies, and
      flies), dramatic decrease in the titers of JH and/or MF promote metamorphosis
      from larvae to adults either directly or through an intermediate pupal stage,
      respectively. JH is absent in crustaceans (lobster, shrimp, crab) and other
      arthropods (chelicerates such as ticks, mites, spiders, scorpions and myriapods
      such as millipede and centipedes). In some crustaceans, molting and reproduction
      is dependent on changing levels of MF. The regulation of sesquiterpenoid
      production is thus crucial in the life cycle of arthropods. Dynamic and complex
      mechanisms have evolved to regulate sesquiterpenoid production. Noncoding RNAs
      such as the microRNAs are primary regulators. This article provides an overview
      of microRNAs that are known to regulate sesquiterpenoid production in arthropods.

PMID- 29355709
TI  - Magnesium sulphate induces preconditioning in preterm rodent models of cerebral
      hypoxia-ischemia.
AB  - BACKGROUND: Brain injury in preterm infants represents a substantial clinical
      problem associated with development of motor impairment, cognitive deficits and
      psychiatric problems. According to clinical studies, magnesium sulphate (MgSO4)
      given to women in preterm labor reduces the risk of cerebral palsy in the
      offspring but the mechanisms behind its neuroprotective effects are still
      unclear. Our aim was to explore whether MgSO4 induces tolerance (preconditioning)
      in the preterm rodent brain. For this purpose we established a model of perinatal
      hypoxia-ischemia (HI) in postnatal day 4 rats and also applied a recently
      developed postnatal day 5 mouse model of perinatal brain injury. METHODS:
      Postnatal day 4 Wistar rats were exposed to unilateral carotid artery ligation
      followed by 60, 70 or 80 min of hypoxia (8% O2). On postnatal day 11, brains were
      collected and macroscopically visible damage as well as white and grey matter
      injury was examined using immunohistochemical staining. Once the model had been
      established, a possible preconditioning protection induced by a bolus MgSO4
      injection prior to 80 min HI was examined 7 days after the insult. Next, a MgSO4
      bolus was injected in C57Bl6 mice on PND 4 followed by exposure to unilateral
      carotid artery ligation and hypoxia, (10% O2) for 70 min on PND 5. Brains were
      collected 7 days after the insult and examined with immunohistochemistry for grey
      and white matter injury. RESULTS: In rats, a 60 min period of hypoxia resulted in
      very few animals with brain injury and although 70 min of hypoxia resulted in a
      higher percentage of injured animals, the brains were marginally damaged. An 80
      min exposure of hypoxia caused cortical tissue damage combined with hippocampal
      atrophy and neuronal loss in the C3 hippocampal layer. In the rat model, MgSO4
      (1.1 mg/g administered i.p. 24 h prior to the induction of HI, resulting in a
      transient serum Mg2+ concentration elevation to 4.1 +/- 0.2 mmol/l at 3 h post
      i.p. injection) reduced brain injury by 74% in grey matter and 64% in white
      matter. In the mouse model, MgSO4 (0.92 mg/g) i.p. injection given 24 h prior to
      the HI insult resulted in a Mg2+ serum concentration increase reaching 2.7 +/-
      0.3 mmol/l at 3 h post injection, which conferred a 40% reduction in grey matter
      injury. CONCLUSIONS: We have established a postnatal day 4 rat model of HI for
      the study of preterm brain injury. MgSO4 provides a marked preconditioning
      protection both in postnatal day 4 rats and in postnatal day 5 mice.

PMID- 29355710
TI  - HBP1 phosphorylation by AKT regulates its transcriptional activity and
      glioblastoma cell proliferation.
AB  - The HMG-box protein 1 (HBP1) is a transcriptional regulator and a potential tumor
      suppressor that controls cell proliferation, differentiation and oncogene
      mediated senescence. In a previous study, we showed that AKT activation through
      the PI3K/AKT/FOXO pathway represses HBP1 expression at the transcriptional level
      in human fibroblasts as well as in cancer cell lines. In the present study, we
      investigated whether AKT could also regulate HBP1 directly. First, AKT1
      phosphorylated recombinant human HBP1 in vitro on three conserved sites, Ser380,
      Thr484 and Ser509. In living cells, we confirmed the phosphorylation of HBP1 on
      residues 380 and 509 using phospho-specific antibodies. HBP1 phosphorylation was
      induced by growth factors, such as EGF or IGF-1, which activated AKT. Conversely,
      it was blocked by treatment of cells with an AKT inhibitor (MK-2206) or by AKT
      knockdown. Next, we observed that HBP1 transcriptional activity was strongly
      modified by mutating its phosphorylation sites. The regulation of target genes
      such as DNMT1, P47phox, p16INK4A and cyclin D1 was also affected. HBP1 had
      previously been shown to limit glioma cell growth. Accordingly, HBP1 silencing by
      small-hairpin RNA increased human glioblastoma cell proliferation. Conversely,
      HBP1 overexpression decreased cell growth and foci formation. This effect was
      amplified by mutations that prevented phosphorylation by AKT, and blunted by
      mutations that mimicked phosphorylation. In conclusion, our results suggest that
      HBP1 phosphorylation by AKT blocks its functions as transcriptional regulator and
      tumor suppressor.

PMID- 29355712
TI  - Divergent behavioural responses to acute hypoxia between individuals and groups
      of naked mole rats.
AB  - Most small rodents reduce energy demand in hypoxia via behavioural strategies.
      For example, animals may reduce their activity, and/or move to colder
      environments or alter huddling strategies to take advantage of anapyretical
      energy savings. Naked mole rats (NMRs) are among the most hypoxia tolerant
      mammals and are highly social; social interactions also have a significant impact
      on behaviour. Therefore, this species offers a fascinating model in which to
      study trade-offs between social interactions and energy conservation in hypoxia.
      We hypothesized that the need to conserve energy in hypoxia supersedes the
      impetus of sociality in this species and predicted that, in hypoxia, behaviour
      would not differ between individuals or groups of NMRs. To test this hypothesis,
      we placed awake, freely behaving NMRs, alone or in groups of 2 or 4, into a
      temperature-controlled apparatus and measured behavioural activity during 1 h
      each of normoxia (21% O2), acute hypoxia (7% O2), and normoxic recovery. We found
      that in normoxia, groups of 4 NMRs were significantly more active in all
      temperatures than were groups of 1-2 NMRs. When exposed to hypoxia, individual
      NMRs were ~50% less active and their speed was reduced relative to normoxic
      levels. Conversely, groups of 2 or 4 NMRs exhibited minor or insignificant
      decreases in time spent active and speed in hypoxia and huddling behaviour was
      not altered. Our findings suggest that social interactions influence behavioural
      strategies employed by NMRs in hypoxia.

PMID- 29355713
TI  - iTRAQ-based differential proteomic analysis of the brains in a rat model of
      delayedcarbon monoxide encephalopathy.
AB  - Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is a
      difficult-to-manage neurological complication that can severely affect the life
      quality of patients. Although the central nervous system (CNS) injuries have been
      reported, the underlying molecular mechanisms are still unclear. Therefore, we
      established a rat model of DEACMP, applying isobaric tags for a relative and
      absolute quantification (iTRAQ)-based proteomics approach to identify
      differentially expressed proteins in cerebral tissue. A total of 170 proteins in
      the CO exposure groups were identified as differentially changed. Bioinformatics
      analysis suggested that these proteins are mainly involved in the biological
      processes, such as energy metabolism and many neurodegenerative diseases. Three
      proteins, Glial fibrillary acidic protein (GFAP), mitochondrial malate
      dehydrogenase (MDHM), and isocitrate dehydrogenase [NAD] subunit alpha (IDH3A),
      were identified as playing important roles in CNS injuries in DEACMP, and were
      successfully confirmed by immunohistochemistry analysis. Our study not only
      offers us new insights into the pathophysiological mechanisms of CNS injuries in
      DEACMP, but also may provide clinicians with important references in early
      prevention and treatment.

PMID- 29355714
TI  - Central beta-turn increases the cell selectivity of imperfectly amphipathic alpha
      helical peptides.
AB  - : Although membrane lytic antimicrobial peptides (AMPs) show enormous potential
      for addressing mounting global antibiotic resistance, therapeutic applications
      are hindered by their weak antimicrobial activity, high toxicity, salt
      sensitivity and poor understanding of structure-activity relationships. To
      investigate the effects of different parameters on the biological activities of
      AMPs, a rational approach was adopted to design a series of short cationic alpha
      helical peptides comprising the Ac-WxKyWxzzyKxWyK-NH2 sequence, where x: cationic
      residues (Arg or Lys), y: hydrophobic residues (Ala, Val, Ile or Leu), and zz:
      beta-turn (rigid D-Pro-Gly turn or flexible Gly-Gly turn). The peptides showed a
      more helical structure as the concentration of membrane-mimetic solution
      increased. The peptide RL with a central D-Pro-Gly turn (x: Arg, y: Lys, zz = D
      Pro-Gly) exhibited broad-spectrum antimicrobial activities (2-8 MUM) against ten
      types of clinically relevant microorganisms and even maintained its activity in
      the presence of physiological salts and showed excellent selectivity toward
      bacterial cells over human red blood cells and mammalian cells. However, the
      toxicity was increased after the removal of D-Pro-Gly turn. Additionally, the
      bactericidal activity was reduced when the D-Pro-Gly turn was replaced by a Gly
      Gly turn. Fluorescence spectroscopy and electron microscopy analyses indicated
      that RL and its derivatives killed microbial cells by permeabilizing the cell
      membrane and damaging membrane integrity. In conclusion, these findings clearly
      generalized a potential method for designing or optimizing AMPs, and the peptide
      RL is a promising therapeutic candidate to combat antibiotic resistance.
      STATEMENT OF SIGNIFICANCE: We proposed a rational approach to design imperfectly
      amphiphilic peptides and identified RL (Ac-WRKLWRpGLKRWLK-NH2) in particular that
      shows strong antibacterial properties, low toxicity and high salt resistance. The
      beta-turn unit inserted into the central position of cationic alpha-helical
      peptides, especially the D-Pro-Gly turn, significantly increase the cell
      selectivity of the synthetic amphiphiles. The findings demonstrate a potential
      method for designing and/or optimizing AMPs, which would facilitate the
      development of strategies to design peptide-based antimicrobial biomaterials in a
      variety of biotechnological and clinical applications.

PMID- 29355716
TI  - Cell-material interactions in tendon tissue engineering.
AB  - : The interplay between cells and materials is a fundamental topic in biomaterial
      based tissue regeneration. One of the principles for biomaterial development in
      tendon regeneration is to stimulate tenogenic differentiation of stem cells. To
      this end, efforts have been made to optimize the physicochemical and bio
      mechanical properties of biomaterials for tendon tissue engineering. However,
      recent progress indicated that innate immune cells, especially macrophages, can
      also respond to the material cues and undergo phenotypical changes, which will
      either facilitate or hinder tissue regeneration. This process has been, to some
      extent, neglected by traditional strategies and may partially explain the
      unsatisfactory outcomes of previous studies; thus, more researchers have turned
      their focus on developing and designing immunoregenerative biomaterials to
      enhance tendon regeneration. In this review, we will first summarize the effects
      of material cues on tenogenic differentiation and paracrine secretion of stem
      cells. A brief introduction will also be made on how material cues can be
      manipulated for the regeneration of tendon-to-bone interface. Then, we will
      discuss the characteristics and influences of macrophages on the repair process
      of tendon healing and how they respond to different materials cues. These
      principles may benefit the development of novel biomaterials provided with
      combinative bioactive cues to activate tenogenic differentiation of stem cells
      and pro-resolving macrophage phenotype. STATEMENT OF SIGNIFICANCE: The progress
      achieved with the rapid development of biomaterial-based strategies for tendon
      regeneration has not yielded broad benefits to clinical patients. In addition to
      the interplay between stem cells and biomaterials, the innate immune response to
      biomaterials also plays a determinant role in tissue regeneration. Here, we
      propose that fine-tuning of stem cell behaviors and alternative activation of
      macrophages through material cues may lead to effective tendon/ligament
      regeneration. We first review the characteristics of key material cues that have
      been manipulated to promote tenogenic differentiation and paracrine secretion of
      stem cells in tendon regeneration. Then, we discuss the potentiality of
      corresponding material cues in activating macrophages toward a pro-resolving
      phenotype to promote tissue repair.

PMID- 29355717
TI  - Localization and promotion of recombinant human bone morphogenetic protein-2
      bioactivity on extracellular matrix mimetic chondroitin sulfate-functionalized
      calcium phosphate cement scaffolds.
AB  - : Localization of recombinant human bone morphogenetic protein-2 (rhBMP-2) with
      continuous and effective osteogenic stimulation is still a great challenge in the
      field of bone regeneration. To achieve this aim, rhBMP-2 was tethered on
      chondroitin sulfate (CS)-functionalized calcium phosphate cement (CPC) scaffolds
      through specific noncovalent interactions. CS, one of the core
      glycosaminoglycans, was covalently conjugated onto CPC scaffolds with the
      assistance of polydopamine (PDA) and further immobilized rhBMP-2 in a biomimetic
      form. The CPC-PDA-CS scaffolds not only controlled the release kinetics and
      presentation state of rhBMP-2 but also effectively increased the expression
      levels of bone morphogenetic protein receptors (BMPRs) and enhanced the
      recognitions of the remaining rhBMP-2 to BMPRs. Strikingly, the rhBMP-2-loaded
      CPC-PDA-CS significantly promoted the cellular surface translocation of BMPRs
      (especially BMPR-IA). In vivo studies demonstrated that, compared with the rhBMP
      2 upon CPC and CPC-PDA, the rhBMP-2 upon CPC-PDA-CS exhibited sustained release
      and induced high quality and more ectopic bone formation. Collectively, these
      results suggest that rhBMP-2 can be localized within CS-functionalized CPC
      scaffolds and exert continuous, long-term, and effective osteogenic stimulation.
      Thus, this work could provide new avenues in mimicking bone extracellular matrix
      microenvironment and localizing growth factor activity for enhanced bone
      regeneration. STATEMENT OF SIGNIFICANCE: A bioinspired chondroitin sulfate (CS)
      functionalized calcium phosphate cement (CPC) platform was developed to tether
      recombinant human bone morphogenetic protein-2 (rhBMP-2), which could exhibit
      continuous, long-term, and effective osteogenic stimulation in bone tissue
      engineering. Compared with rhBMP-2-loaded CPC, the rhBMP-2-loaded CPC
      polydopamine-CS scaffolds induced higher expression of bone morphogenetic protein
      receptors (BMPRs), greater cellular surface translocation of bone morphogenetic
      protein receptor-IA, higher binding affinity of BMPRs/rhBMP-2, and thus higher
      activation of the drosophila gene mothers against decapentaplegic protein-1/5/8
      (Smad1/5/8) and extracellular-regulated protein kinases-1/2 (ERK1/2) signaling.
      This work can provide new guidelines for the design of BMP-2-based bioactive
      materials for bone regeneration.

PMID- 29355715
TI  - Short peptide analogs as alternatives to collagen in pro-regenerative corneal
      implants.
AB  - : Short collagen-like peptides (CLPs) are being proposed as alternatives to full
      length collagen for use in tissue engineering, on their own as soft hydrogels, or
      conjugated to synthetic polymer for mechanical strength. However, despite
      intended clinical use, little is known about their safety and efficacy, mechanism
      of action or degree of similarity to the full-length counterparts they mimic.
      Here, we show the functional equivalence of a CLP conjugated to polyethylene
      glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in
      promoting stable regeneration of corneal tissue and nerves in a pre-clinical mini
      pig model. We also show that these peptide analogs exerted their pro-regeneration
      effects through stimulating extracellular vesicle production by host cells. Our
      results support future use of CLP-PEG implants for corneal regeneration,
      suggesting the feasibility of these or similar peptide analogs in clinical
      application in the eye and other tissues. STATEMENT OF SIGNIFICANCE: Although
      biomaterials comprising full-length recombinant human collagen and extracted
      animal collagen have been evaluated and used clinically, these macromolecules
      provide only a limited number of functional groups amenable to chemical
      modification or crosslinking and are demanding to process. Synthetic,
      customizable analogs that are functionally equivalent, and can be readily scaled
      up are therefore very desirable for pre-clinical to clinical translation. Here,
      we demonstrate, using cornea regeneration as our test bed, that collagen-like
      peptides conjugated to multifunctional polyethylene glycol (CLP-PEG) when grafted
      into mini-pigs as corneal implants were functionally equivalent to recombinant
      human collagen-based implants that were successfully tested in patients. We also
      show for the first time that these materials affected regeneration through
      stimulation of extracellular vesicle production by endogenous host cells that
      have migrated into the CLP-PEG scaffolds.

PMID- 29355718
TI  - Trivalent chromium incorporated in a crystalline calcium phosphate matrix
      accelerates materials degradation and bone formation in vivo.
AB  - : Remodeling of calcium phosphate bone cements is a crucial prerequisite for
      their application in the treatment of large bone defects. In the present study
      trivalent chromium ions were incorporated into a brushite forming calcium
      phosphate cement in two concentrations (10 and 50 mmol/mol beta-tricalcium
      phosphate) and implanted into a femoral defect in rats for 3 and 6 month, non
      modified brushite was used as reference. Based on our previous in vitro findings
      indicating both an enhanced osteoclastic activity and cytocompatibility towards
      osteoprogenitor cells we hypothesized a higher in vivo remodeling rate of the
      Cr3+ doped cements compared to the reference. A significantly enhanced
      degradation of the modified cements was evidenced by micro computed tomography, X
      ray and histological examinations. Furthermore the formation of new bone tissue
      after 6 month of implantation was significantly increased from 29% to 46% during
      remodeling of cements, doped with the higher Cr3+ amount. Time of flight
      secondary ion mass spectrometry (ToF-SIMS) of histological sections was applied
      to investigate the release of Cr3+ ions from the cement after implantation and to
      image their distribution in the implant region and the surrounding bone tissue.
      The relatively weak incorporation of chromium into the newly formed bone tissue
      is in agreement to the low chromium concentrations which were released from the
      cements in vitro. The faster degradation of the Cr3+ doped cements was also
      verified by ToF-SIMS. The positive effect of Cr3+ doping on both degradation and
      new bone formation is discussed as a synergistic effect of Cr3+ bioactivity on
      osteoclastic resorption on one hand and improvement of cytocompatibility and
      solubility by structural changes in the calcium phosphate matrix on the other
      hand. STATEMENT OF SIGNIFICANCE: While biologically active metal ions like
      strontium, magnesium and zinc are increasingly applied for the modification of
      ceramic bone graft materials, the present study is the first report on the
      incorporation of low doses of trivalent chromium ions into a calcium phosphate
      based biomaterial and testing of its performance in bone defect regeneration in
      vivo. Chromium(III)-doped calcium phosphate bone cements show improved
      cytocompatibility and both degradation rate and new bone formation in vivo are
      significantly increased compared to the reference cement. This important
      discovery might be the starting point for the application of trivalent chromium
      salts for the modification of bone graft materials to increase their remodelling
      rate.

PMID- 29355719
TI  - Procancerogenic activity of senescent cells: A case of the peritoneal
      mesothelium.
AB  - Human peritoneal mesothelial cells belong to a narrow group of somatic cells in
      which both the triggers and the mechanisms of senescence have already been well
      defined. Importantly, senescent mesothelial cells have been found in the
      peritoneal cavity in vivo. From a clinical point of view, peritoneal mesothelial
      cells have been recognized as playing a critical role in the intraperitoneal
      development of tumor metastases. The pro-cancerogenic behavior of mesothelial
      cells is even more pronounced when the cells exhaust their proliferative capacity
      and become senescent. In this review, we summarize the current state of art
      regarding the contribution of peritoneal mesothelial cells in the progression of
      ovarian, colorectal, and pancreatic carcinomas, with particular attention paid to
      the cancer-promoting activity of their senescent counterparts. Moreover, we
      delineate the mechanisms, mediators, and signaling pathways that are engaged by
      the senescent mesothelial cells to support such vital elements of cancer
      progression as adhesion, proliferation, migration, invasion, epithelial
      mesenchymal transition, and angiogenesis. Finally, we discuss the experimental
      evidence regarding both natural and synthetic compounds that may either prevent
      or restrict cancer development by delaying senescence of mesothelial cells.

PMID- 29355720
TI  - Zileuton alleviates acute cisplatin nephrotoxicity: Inhibition of lipoxygenase
      pathway favorably modulates the renal oxidative/inflammatory/caspase-3 axis.
AB  - OBJECTIVE: The current study investigated for the first time the possible
      beneficial effect of zileuton, a selective 5-lipoxygenase inhibitor (5-LOX),
      against cisplatin-induced acute renal failure. METHODOLOGY: Male Sprague-Dawley
      rats (180-200 g) were administered cisplatin once (5 mg/kg, i.p.) alone or
      combined with oral zileuton (10 mg/kg, given twice; 1 h before and 12 h after
      cisplatin). RESULTS: Compared with control rats, acute cisplatin administration
      caused significant increases of BUN (33.76 +/- 7.74 vs 61.88 +/- 11.35 mg/dl),
      serum creatinine (0.61 +/- 0.21 vs 1.56 +/- 0.28 mg/dl), renal levels of MDA
      (6.40 +/- 1.04 vs 20.52 +/- 2.18 nmol/g tissue), NOx (3.45 +/- 1.20 vs 17.70 +/-
      2.27 nmol/g tissue), TNF-alpha (6.71 +/- 0.66 vs 23.71 +/- 3.41 pg/g tissue), MPO
      (0.87 +/- 0.09 vs 3.12 +/- 0.41 U/mg tissue protein) and renal caspase-3 activity
      (2.81 +/- 0.37 vs 12.70 +/- 2.94 U/mg tissue protein). Whereas, total SOD
      activity (1.99 +/- 0.53 vs 0.79 +/- 0.06 U/mg tissue protein) and IL-10 (110.98
      +/- 19.70 vs 62.34 +/- 14.42 pg/g tissue) were significantly decreased. Cisplatin
      induced nephrotoxicity was further confirmed histopathologically (tubular
      necrosis, cystic dilatation of renal tubules, vacuolar degeneration of renal
      tubular epithelium with perivascular oedema, and interstitial fibrosis). These
      changes were accompanied by alteration in 5-LOX pathway manifested as elevated
      renal levels of 5-LOX, LTD4 and LTB4. Simultaneous administration of zileuton to
      the cisplatin-treated rats reversed the deleterious renal insults and restored
      the measured parameters near to control values. CONCLUSIONS: These data establish
      the first experimental evidence that zileuton abrogates cisplatin nephrotoxicity
      in rats probably via the inhibition of detrimental actions of 5-LOX products,
      thus favorably affecting renal oxidative/inflammatory/caspase-3 axis. Based on
      current findings, the therapeutic prospect of zileuton for this purpose is
      recommended.

PMID- 29355711
TI  - Implication of the Kallikrein-Kinin system in neurological disorders: Quest for
      potential biomarkers and mechanisms.
AB  - Neurological disorders represent major health concerns in terms of comorbidity
      and mortality worldwide. Despite a tremendous increase in our understanding of
      the pathophysiological processes involved in disease progression and prevention,
      the accumulated knowledge so far resulted in relatively moderate translational
      benefits in terms of therapeutic interventions and enhanced clinical outcomes.
      Aiming at specific neural molecular pathways, different strategies have been
      geared to target the development and progression of such disorders. The
      kallikrein-kinin system (KKS) is among the most delineated candidate systems due
      to its ubiquitous roles mediating several of the pathophysiological features of
      these neurological disorders as well as being implicated in regulating various
      brain functions. Several experimental KKS models revealed that the inhibition or
      stimulation of the two receptors of the KKS system (B1R and B2R) can exhibit
      neuroprotective and/or adverse pathological outcomes. This updated review
      provides background details of the KKS components and their functions in
      different neurological disorders including temporal lobe epilepsy, traumatic
      brain injury, stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis
      and glioma. Finally, this work will highlight the putative roles of the KKS
      components as potential neurotherapeutic targets and provide future perspectives
      on the possibility of translating these findings into potential clinical
      biomarkers in neurological disease.

PMID- 29355721
TI  - Selecting the Best Donor for Haploidentical Transplant: Impact of HLA, Killer
      Cell Immunoglobulin-Like Receptor Genotyping, and Other Clinical Variables.
AB  - The use of post-transplant cyclophosphamide (PTCy)-based haploidentical (haplo)
      transplant is increasing worldwide. However, because multiple potential haplo
      donors are usually available, data-driven guidance is clearly needed to help
      transplant centers prioritize donors. To that end, we retrospectively analyzed
      208 consecutive donor-recipient pairs receiving PTCy-based haplo transplant at a
      single institution. Median recipient and donor age were 52 years (range, 19 to
      75) and 38 years (range, 15 to 73), peripheral blood stem cell was the stem cell
      source in 66%, and myeloablative conditioning was used in 41%. Median follow-up
      for surviving patients was 33 months (range, 7 to 130). Donor variables analyzed
      included age, sex, relationship, cytomegalovirus (CMV) status, ABO compatibility,
      HLA disparity, and several natural killer (NK) alloreactivity models.
      Multivariate Cox analysis was used to adjust for known patient, disease, and
      transplant covariates. Donor characteristics independently associated with
      improved survival included presence of HLA-DR mismatch, HLA-DP nonpermissive
      mismatch, killer cell immunoglobulin-like receptor (KIR) receptor-ligand
      mismatch, and KIR B/x haplotype with KIR2DS2. Donor characteristics associated
      with inferior survival included parental donor relationship and the use of a CMV
      seronegative donor for a CMV-seropositive patient. Increased HLA disparity
      (>=4/10 HLA allelic mismatches [graft-versus-host direction]) resulted in relapse
      protection at the expense of increased nonrelapse mortality with no associated
      survival effect. We further propose a donor risk factor scoring system to permit
      a more evidence-based selection algorithm for potential haplo donors. This large,
      single-institution analysis demonstrates the importance of HLA-DR/HLA-DP
      disparity, NK alloreactivity, and other clinical variables in the haplo donor
      selection process and suggests that KIR and HLA-DP genotyping should be performed
      routinely for haplo donor selection.

PMID- 29355722
TI  - Predicting cardiac safety using human induced pluripotent stem cell-derived
      cardiomyocytes combined with multi-electrode array (MEA) technology: A conference
      report.
AB  - Safety pharmacology studies that evaluate drug candidates for potential
      cardiovascular liabilities remain a critical component of drug development. Human
      induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have recently
      emerged as a new and promising tool for preclinical hazard identification and
      risk assessment of drugs. Recently, Pluriomics organized its first User Meeting
      entitled 'Combining Pluricyte(r) Cardiomyocytes & MEA for Safety Pharmacology
      applications', consisting of scientific sessions and live demonstrations, which
      provided the opportunity to discuss the application of hiPSC-CMs (Pluricyte(r)
      Cardiomyocytes) in cardiac safety assessment to support early decision making in
      safety pharmacology. This report summarizes the outline and outcome of this
      Pluriomics User Meeting, which took place on November 24-25, 2016 in Leiden (The
      Netherlands). To reflect the content of the communications presented at this
      meeting we have cited key scientific articles and reviews.

PMID- 29355723
TI  - A case of CHARGE syndrome associated with hyperinsulinemic hypoglycemia in
      infancy.
AB  - CHARGE syndrome is a rare autosomal dominant disorder involving multiple organs.
      Chromodomain helicase DNA binding protein-7 (CHD7) is a major causative gene of
      CHARGE syndrome. We herein report a male infant born at full term with asphyxia
      who was diagnosed with CHARGE syndrome based on the typical anomalies. He showed
      a poor sucking ability and suffered from continuous hypoglycemia in early
      infancy, ultimately requiring tube feeding. While in a hypoglycemic status,
      inappropriate high insulin and low growth hormone levels were noticed. Growth
      hormone replacement therapy partially increased his blood glucose levels, but
      asymptomatic hypoglycemia with hyperinsulinemia was occasionally noticed.
      Additional diazoxide treatment stabilized his blood level to within the normal
      range. A genetic analysis of CHD7 showed the novel heterozygous monoallelic
      mutation c.2990delT causing a reading frameshift p.Leu997Trpfs*15 in exon 12.
      This case shows that patients with CHARGE syndrome caused by a CHD7 mutation may
      present with persistent hyperinsulinemic hypoglycemia, just like other dysmorphic
      syndromes genetically caused by aberrations in chromatin remodeling.

PMID- 29355724
TI  - PRRX1 Rs3903239 polymorphism and atrial fibrillation in a Greek population.

PMID- 29355725
TI  - Cellular therapies for chronic ischemic heart failure.
AB  - The development of stem cell therapies for chronic ischemic heart failure is
      highly sought after to attempt to improve morbidity and mortality of this
      prevalent disease. This article reviews clinical trials that investigate stem
      cell therapy for chronic ischemic heart failure. To generate this review article,
      PubMed was searched using keywords "stem cell therapy heart failure" with the
      article type "Clinical Trial" selected on 10/04/2016. The raw search yielded 156
      articles; 53 articles were selected for inclusion in the review between the
      original literature search and manual research/cross-referencing. Additional
      reviews and original articles were also manually researched and cross-referenced.
      Cellular-based therapies utilizing peripheral blood progenitor cells, bone marrow
      cells, mesenchymal stem cells, cells of cardiac origin, and embryonic stem cells
      have yielded mixed results, but some studies have shown modest efficacy. Skeletal
      myoblasts raised concerns about safety due to arrhythmias. Optimizing cell type
      and delivery method will be of critical importance in enhancing efficacy of
      therapy within various subsets of chronic ischemic heart failure patients.
      Although much more work needs to be done to optimize treatment strategies,
      developing stem cell therapies for chronic ischemic heart failure could be of
      critical importance to lessen the impactful health burden that heart failure has
      on patients and society.

PMID- 29355726
TI  - Pathways to depression by age 16 years: Examining trajectories for self-reported
      psychological and somatic phenotypes across adolescence.
AB  - BACKGROUND: Sex differences in rates of depression emerge during adolescence.
      However, it is unclear whether symptom patterns and trajectories differ
      significantly according to gender in youth. Barriers to research include the fact
      that most self-report tools are weighted towards psychological rather than
      somatic symptoms. METHODS: Data were collected on symptoms of depression in about
      1800 individuals at ages 12, 14 and 16 years. Odds ratios and 95% confidence
      intervals were used to examine the trajectory of psychological and somatic
      phenotypes and self-reported depression caseness over time. RESULTS: At age 12,
      24% of participants met criteria for self-reported depression caseness. Although
      there was only a small incremental increase in the prevalence over time (about
      5%), 57% of participants met criteria for self-reported depression caseness at
      least once. Generic symptoms at age 12 were associated with depression
      longitudinally, although early transition to caseness was reported in females
      only. Categorization as a psychological phenotype at age 12 predicted depression
      at age 14 and/or 16 years, especially in females. The somatic phenotype was more
      common in males, but showed a weaker association with self-reported depression
      caseness over time. LIMITATIONS: Depression was assessed by self-report; only 30%
      of participants had ratings for age 12, 14 and 16. CONCLUSIONS: Although sub
      threshold psychological and somatic syndromes often co-occur in cases of self
      reported depression in adolescence, longitudinally they may represent independent
      symptom trajectories. However, it is important to remember that self-reported
      depression is indicative of, but not confirmation of a depressive episode that
      meets diagnostic criteria.

PMID- 29355728
TI  - Stressful life events and depressive symptoms in mothers and fathers of young
      children.
AB  - BACKGROUND: Parents of young children generally report more depressive symptoms
      than parents of adult children or people without children, mainly because the
      presence of young children increases exposure to significant stressors (such as
      stressful life events). However, most studies on the depressogenic role of
      stressful life events in parents of young children have focussed on mothers.
      METHODS: Using data from 1138 families with young children in Norway, we
      investigated gender differences in the effect of stressful life events after a
      child's birth on the development of parental depressive symptoms in 3 follow-ups
      at child's ages 3-6 years. We also explored if gender differences in disposition
      (personality) may explain any gender differences in the depressogenic effect of
      life events. RESULTS: Nesting parents within families, we found a female gender
      bias for both neuroticism and depressive symptoms but no gender difference in the
      number of life events reported. Importantly, the number of stressful life events
      predicted the level and course of depressive symptoms similarly for mothers and
      fathers. Personality traits did not change the association between stressful life
      events and depressive symptoms in either mothers or fathers. LIMITATIONS: Given
      the study design, causality cannot be inferred. CONCLUSIONS: There was no gender
      difference in the depressogenic effect of stressful life events in our sample.
      There was no evidence for a female dispositional sensitivity to the depressogenic
      effect of stressful life events, either. Stressful life events put both mothers
      and fathers of young children at risk of depression.

PMID- 29355727
TI  - One-year follow-up of a randomized controlled trial of sertraline and cognitive
      behavior group therapy in depressed primary care patients (MIND study).
AB  - BACKGROUND: The long-term course of symptoms in patients with mild-to-moderate
      depression is not well understood. A 12-month-follow-up analysis was performed on
      those participants from a randomized controlled 10-week trial (RCT, MIND-study),
      who had received either treatment with an antidepressant (sertraline) or a
      psychotherapeutic intervention (group cognitive-behavioral therapy (CBT)).
      METHODS: The longitudinal interval follow-up evaluation (LIFE) was applied to 77
      patients with mild-to moderate depression. The primary outcome was the number of
      weeks in the one-year follow-up period spent completely recovered from all
      depressive symptoms. Functional outcome was measured with the Global Assessment
      of Functioning (GAF) scale. Further outcomes were relapse and remission rates
      based on weekly psychiatric rating scales (PSR) and the number of weeks in the
      follow-up period during which patients had a depressive disorder or subthreshold
      symptoms of depression. RESULTS: Patients with acute treatment (10 weeks) with
      SSRI and those with acute treatment with CBT (also 10 weeks) did not differ
      significantly concerning the number of weeks in the follow-up period in which
      they were completely recovered (primary outcome) (SSRI: 31.6 weeks (standard
      deviation (SD): 23.7), CBT: 27.8 weeks (SD: 24.3)). Sertraline was superior to
      CBT regarding GAF scores by trend (p = 0.06). LIMITATIONS: The generalizability
      of the findings is limited by the moderate sample size and missing values (LIFE).
      CONCLUSIONS: Sertraline and group CBT have similar anti-depressive effects in the
      long-term course of mild-to-moderate depression. Regarding long-term global
      functioning, sertraline seems to be slightly superior to CBT.

PMID- 29355729
TI  - Pre-disaster PTSD as a moderator of the relationship between natural disaster and
      suicidal ideation over time.
AB  - BACKGROUND: Natural disasters are associated with a variety of negative health
      consequences, including enhanced suicide risk. Factors that moderate the
      relationship between disaster exposure and enhanced suicide risk are unknown. The
      aim of the current study was to determine whether pre-disaster PTSD moderates the
      association between change over time in thoughts of death, suicidal ideation
      (SI), suicide plans, and suicide attempts (SA) from pre- to post-disaster.
      METHODS: Participants (n = 2832) were recruited from Chile as part of the larger
      PREDICT study and completed a measure of lifetime PTSD and panic disorder at
      baseline and a lifetime death/suicide measure at baseline in 2003 and again 6,
      12, and 24 months later (i.e. "pre-disaster"). One year following a major
      earthquake and tsunami in 2010 (i.e., "post-disaster"), participants completed
      another death/suicide measure. RESULTS: Both those with and without pre-disaster
      PTSD experienced significant increases in SI from pre- to post-disaster. However,
      pre-disaster PTSD was associated with significantly accelerated increases in
      thoughts of death and SI from pre-to post-disaster. At nearly all time-points,
      pre-disaster PTSD was associated with higher thoughts of death and SI, suicide
      planning, and SA. In contrast, panic disorder did not moderate the association
      between time and changes in SI. LIMITATIONS: There was a long time-gap between
      pre-disaster and post-disaster, with limited data about what occurred during this
      time. CONCLUSION: Pre-disaster PTSD is an important predictor of increased SI
      following a natural disaster, and groups with pre-disaster PTSD should be
      prioritized for receipt of mental health resources following a natural disaster.

PMID- 29355730
TI  - Extensive severe fever with thrombocytopenia syndrome virus contamination in
      surrounding environment in patient rooms.
AB  - OBJECTIVES: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging
      tick-borne disease in Korea and China. Although there is previous evidence of
      person-to-person transmission via direct contact with body fluids, the role of
      environmental contamination by SFTS virus (SFTSV) in healthcare settings has not
      been established. We therefore investigated the contamination of the healthcare
      environment by SFTSV. METHODS: We investigated the possible contamination of
      hospital air and surfaces with SFTSV transmission by collecting air and swabbing
      environmental surface samples in two hospitals treating six SFTS patients between
      March and September 2017. The samples were tested using real-time RT-PCR for SFTS
      M and S segments. RESULTS: Of the six SFTS patients, four received mechanical
      ventilation and three died. Five rooms were occupied by those using mechanical
      ventilation or total plasma exchange therapy in isolation rooms without negative
      pressure and one room was occupied by a patient bedridden due to SFTS. SFTSV was
      detected in 14 (21%) of 67 swab samples. Five of 24 swab samples were obtained
      from fomites including stethoscopes, and 9 of 43 were obtained from fixed
      structures including doorknobs and bed guardrails. Some samples from fixed
      structures such as television monitors and sink tables were obtained in areas
      remote from the patients. SFTSV RNA was not detected in five air samples from
      three patients' rooms. CONCLUSIONS: Our data suggest that SFTSV contamination was
      extensive in surrounding environments in SFTS patients' rooms. Therefore, more
      strict isolation methods and disinfecting procedures should be considered when
      managing SFTS patients.

PMID- 29355731
TI  - Human babesiosis in Southeast China: A case report.
AB  - A 60-year-old female patient living in Southeast China presented with persistent
      fever, chills, night sweats, fatigue, and dizziness of 12-day duration. Blood
      tests showed neutropenia, thrombocytopenia, and active hemolytic anemia, with
      elevated C-reactive protein. Broad-spectrum antibiotics were administered for a
      possible diagnosis of sepsis, without any response. Malaria was initially
      diagnosed after visualizing intraerythrocytic ring-shaped parasites in bone
      marrow and blood smears. The patient resided in an area of unstable endemicity
      for Plasmodium falciparum. Blood samples were sent to the Centers for Disease
      Control and Prevention and a definitive diagnosis of human babesiosis was made
      using Babesia microti-specific PCR. Chloroquine phosphate and clindamycin were
      started and the patient became normothermic. However, due to the intolerable
      adverse effects of the antibiotics, intravenous azithromycin was given as an
      alternative. The patient recovered from fever and hemolysis, and repeated
      peripheral blood smears showed hemoparasite clearance. Cases of human babesiosis
      are rarely reported and probably under-diagnosed in China; therefore, improving
      our understanding of this disease as a newly emerging public health threat is
      imperative.

PMID- 29355732
TI  - The quest for endothelial atypical cannabinoid receptor: BKCa channels act as
      cellular sensors for cannabinoids in in vitro and in situ endothelial cells.
AB  - Endothelium-dependent component of cannabinoid-induced vasodilation has been
      postulated to require G-protein-coupled non-CB1/CB2 endothelial cannabinoid (eCB)
      receptor. GPR18 was proposed as a candidate for eCBR. To address the hypothesis
      that the effects attributed to eCBR are mediated by G-protein-coupled receptor
      (GPCR)-independent targets, we studied the electrical responses in endothelial
      cells, focusing on BKCa channels. In patches excised from endothelial-derived
      EA.hy926 cells, N-arachidonoyl glycine (NAGly) and abnormal cannabidiol (abn
      cbd), prototypical agonists for eCB receptor, stimulate single BKCa activity in a
      concentration- and Ca2+-dependent manner. The postulated eCB receptor inhibitors
      rimonabant and AM251 were found to inhibit basal and stimulated by NAGly- and abn
      cbd BKCa activity in cell-free patches. In isolated mice aortas, abn-cbd and
      NAGly produced endothelial cell hyperpolarization that was sensitive to
      paxilline, a selective BKCa inhibitor, but not to GPR18 antibody, and mimicked by
      NS1619, a direct BKCa opener. In excised patches from mice aortic endothelium,
      single channel activity with characteristics similar to BKCa was established by
      the addition of abn-cbd and NAGly. We conclude that the two cannabinoids abn-cbd
      and NAGly initiate a GPR18-independent activation of BKCa channels in mice aortic
      endothelial cells that might contribute to vasodilation to cannabinoids.

PMID- 29355733
TI  - A new approach to detect the coding rule of the cortical spiking model in the
      information transmission.
AB  - Investigation of the role of the local field potential (LFP) fluctuations in
      encoding the received sensory information by the nervous system remains largely
      unknown. On the other hand, transmission of these translation rules in
      information transmission between the structure of sensory stimuli and the
      cortical oscillations to the bio-inspired artificial neural networks operating at
      the efficiency of the nervous system is still a vague puzzle. In order to move
      towards this important goal, computational neuroscience tools can be useful so,
      we simulated a large-scale network of excitatory and inhibitory spiking neurons
      with synaptic connections consisting of AMPA and GABA currents as a model of
      cortical populations. Spiking network was equipped with spike-based unsupervised
      weight optimization based on the dynamical behavior of the excitatory (AMPA) and
      inhibitory (GABA) synapses using Spike Timing Dependent Plasticity (STDP) on the
      MNIST benchmark and we specified how the generated LFP by the network contained
      information about input patterns. The main result of this article is that the
      calculated coefficients of Prolate spheroidal wave functions (PSWF) from the
      input pattern with mean square error (MSE) criterion and power spectrum of LFP
      with maximum correntropy criterion (MCC) are equal. The more important result is
      that 82.3% of PSWF coefficients are the same as the connecting weights of the
      cortical neurons to the classifying neurons after the completion of the training
      process. Higher compliance percentage of coefficients with synaptic weights
      (82.3%) gives the expectance us that this coding rule will be able to extend to
      biological systems. Eventually, we introduced the cortical spiking network as an
      information channel, which transmits the information of the input pattern in the
      form of PSWF coefficients to the power spectrum of the output generated LFP.

PMID- 29355734
TI  - Inhibition of autophagy potentiates the apoptosis-inducing effects of
      photodynamic therapy on human colon cancer cells.
AB  - BACKGROUND: Photodynamic therapy (PDT) has been reported to be a promising
      therapy for colon cancer because of its substantial safety features and its
      ability to induce a systematic reaction rather than local effects on the focal
      lesion in the intestine. Autophagy and apoptosis play important roles in the
      response to PDT. However, the role of autophagy after PDT treatment has not yet
      been clarified. METHODS: In this study, we investigated the relationship between
      apoptosis and autophagy in porphyrin IX (PpIX)-mediated PDT (PpIX-PDT) in HCT116
      colon cancer cells. PpIX-PDT decreased cell viability in a concentration- and
      light dose-dependent manner. RESULTS: PpIX-PDT results in nuclear condensation,
      increased the expression of Caspase-3, Bax, and PARP, and decreased expression of
      Bcl-2. PpIX-PDT also induces the double membrane autophagosome, up-regulates
      LC3B, Atg7, Beclin-1, and Bcl-2 expression and down-regulates P62 expression.
      Inhibition of autophagy using chloroquine (CQ) or Atg7 knockdown with a shRNA
      enhances apoptotic cell death. Based on these findings, autophagy plays a self
      protective role in HCT116 cells in response to PpIX-PDT treatment. DISCUSSION:
      Both autophagy and apoptosis were induced by PpIX-PDT in HCT116 cells, and the
      inhibition of autophagy strengthened the proapoptotic effect of PpIX-PDT. Thus,
      the appropriate modulation of autophagy may be as a potential therapeutic target
      for colon cancer cells treated with PpIX-PDT.

PMID- 29355735
TI  - Photodynamic therapy using 5-aminolevulinic acid triggered DNA damage of
      adenocarcinoma breast cancer and hepatocellular carcinoma cell lines.
AB  - Targeting cancer cells with photosensitizer (PS) excited by appropriate laser
      irradiation to release singlet oxygen as a photodynamic therapy (PDT) remains a
      challenge. This research aimed to assess the cytogenetic potential of 5
      aminolevulinic acid (5-ALA) activated with laser irradiation (5-ALA/PDT) to
      damage the intact DNA of adenocarcinoma breast cancer cell line (MCF-7) and
      hepatocellular carcinoma cell line (HepG2). Cancer cells were treated with 0.5
      and 1 mM 5-ALA for 4 h, the precursor of the photochemical protoporphyrin IX
      (PpIX), and then exposed to laser irradiation at 633 nm and 0.25 W for 4 min
      before incubation for 24 h. Cytotoxicity of cancer cells was assessed using
      trypan blue exclusion assay. Genotoxicity was recorded by micronucleus test and
      comet assay. Both 5-ALA and laser irradiation, separately, were nontoxic on
      cancer cell lines, however, 5-ALA/PDT enhanced cell death in a concentration
      dependent manner. Also, 5-ALA/PDT generated high percentages of micronuclei in
      MCF-7 and HepG2 cell lines as recorded in binucleated cells. Similarly, the mean
      percentages of DNA damage and tail moment ratio were intensified extremely in
      cancer cell lines treated with 5-ALA/PDT rather than non-treated cells or cells
      treated by 5-ALA or laser irradiation separately. In conclusion, the singlet
      oxygen of 5-ALA targets DNA of cancer cells when activated by laser irradiation.
      Therefore, photodynamic therapy is an applicable process to damage DNA
      effectively during M-phase and prohibit cancer cells proliferation.

PMID- 29355736
TI  - A role for Hippo/YAP-signaling in FGF-induced lens epithelial cell proliferation
      and fibre differentiation.
AB  - Recent studies indicate an important role for the transcriptional co-activator
      Yes-associated protein (YAP), and its regulatory pathway Hippo, in controlling
      cell growth and fate during lens development; however, the exogenous factors that
      promote this pathway are yet to be identified. Given that fibroblast growth
      factor (FGF)-signaling is an established regulator of lens cell behavior, the
      current study investigates the relationship between this pathway and Hippo/YAP
      signaling during lens cell proliferation and fibre differentiation. Rat lens
      epithelial explants were cultured with FGF2 to induce epithelial cell
      proliferation or fibre differentiation. Immunolabeling methods were used to
      detect the expression of Hippo-signaling components, Total and Phosphorylated
      YAP, as well as fibre cell markers, Prox-1 and beta-crystallin. FGF-induced lens
      cell proliferation was associated with a strong nuclear localisation of Total-YAP
      and low-level immuno-staining for phosphorylated-YAP. FGF-induced lens fibre
      differentiation was associated with a significant increase in cytoplasmic
      phosphorylated YAP (inactive state) and enhanced expression of core Hippo
      signaling components. Inhibition of YAP with Verteporfin suppressed FGF-induced
      lens cell proliferation and ablated cell elongation during lens fibre
      differentiation. Inhibition of either FGFR- or MEK/ERK-signaling suppressed FGF
      promoted YAP nuclear translocation. Here we propose that FGF promotes Hippo/YAP
      signaling during lens cell proliferation and differentiation, with FGF-induced
      nuclear-YAP expression playing an essential role in promoting the proliferation
      of lens epithelial cells. An FGF-induced switch from proliferation to
      differentiation, hence regulation of lens growth, may play a key role in
      mediating Hippo suppression of YAP transcriptional activity.

PMID- 29355737
TI  - 670nm light treatment following retinal injury modulates Muller cell gliosis:
      Evidence from in vivo and in vitro stress models.
AB  - Photobiomodulation (PBM) with 670 nm light has been shown to accelerate wound
      healing in soft tissue injuries, and also to protect neuronal tissues. However,
      little data exist on its effects on the non-neuronal components of the retina,
      such as Muller cells (MCs), which are the principal macroglia of the retina that
      play a role in maintaining retinal homeostasis. The aim of this study was to
      explore the effects of 670 nm light on activated MCs using in vivo and in vitro
      stress models. Adult Sprague-Dawley rats were exposed to photo-oxidative damage
      (PD) for 24 h and treated with 670 nm light at 0, 3 and 14 days after PD. Tissue
      was collected at 30 days post-PD for analysis. Using the in vitro scratch model
      with a human MC line (MIO-M1), area coverage and cellular stress were analysed
      following treatment with 670 nm light. We showed that early treatment with 670 nm
      light after PD reduced MC activation, lowering the retinal expression of GFAP and
      FGF-2. 670 nm light treatment mitigated the production of MC-related pro
      inflammatory cytokines (including IL-1beta), and reduced microglia/macrophage
      (MG/MPhi) recruitment into the outer retina following PD. This subsequently
      decreased photoreceptor loss, slowing the progression of retinal degeneration. In
      vitro, we showed that 670 nm light directly modulated MC activation, reducing
      rates of area coverage by suppressing cellular proliferation and spreading. This
      study indicates that 670 nm light treatment post-injury may have therapeutic
      benefit when administered shortly after retinal damage, and could be useful for
      retinal degenerations where MC gliosis is a feature of disease progression.

PMID- 29355738
TI  - Carbonic anhydrase II does not exhibit Nitrite reductase or Nitrous Anhydrase
      Activity.
AB  - Carbonic anhydrase II (CA II) is a zinc metalloenzyme that catalyzes the
      reversible interconversion of water and CO2 to bicarbonate and a proton. CA II is
      abundant in most cells, and plays a role in numerous processes including gas
      exchange, epithelial ion transport, respiration, extra- and intracellular pH
      control, and vascular regulation. Beyond these CO2 and pH-linked roles, it has
      been postulated that CA II might also reduce nitrite (NO2-) to nitric oxide (NO),
      as bicarbonate and NO2- both exhibit sp2 molecular geometry and NO also plays an
      important role in vasodilation and regulation of blood pressure. Indeed, previous
      studies by Aamand et al. have shown that bovine CA II (BCA II) possesses nitrite
      dehydration activity and paradoxically demonstrated that CA inhibitors (CAIs)
      such as dorzolamide and acetazolamide significantly increased NO production
      (Aamand et al., 2009; Nielsen and Fago, 2015) [1,2]. Hence, the goal of this work
      was to revisit these studies using the same experimental conditions as Aamand et
      al. measuring NO generation by two methods, and to examine the structure of CA II
      in complex with NO2- in the presence and absence of dorzolamide. Our results
      contradict the previous findings and indicate that CA II does not exhibit nitrite
      reductase or dehydration activity, and that this is not enhanced in the presence
      of CA inhibitors. In addition, a structural examination of BCA II in complex with
      NO2- and superimposed with dorzolamide demonstrates that CA inhibitor binding at
      the active site to the zinc moiety blocks potential NO2- binding.

PMID- 29355739
TI  - Nicotine induces apoptosis in human osteoblasts via a novel mechanism driven by
      H2O2 and entailing Glyoxalase 1-dependent MG-H1 accumulation leading to TG2
      mediated NF-kB desensitization: Implication for smokers-related osteoporosis.
AB  - Nicotine contained in cigarette smoke contributes to the onset of several
      diseases, including osteoporosis, whose emerging pathogenic mechanism is
      associated with osteoblasts apoptosis. Scanty information is available on the
      molecular mechanisms of nicotine on osteoblasts apoptosis and, consequently, on
      an important aspect of the pathogenesis of smokers-related osteoporosis.
      Glyoxalase 1 (Glo1) is the detoxification enzyme of methylglyoxal (MG), a major
      precursor of advanced glycation end products (AGEs), potent pro-apoptotic agents.
      Hydroimidazolone (MG-H1) is the major AGE derived from the spontaneous MG
      adduction of arginine residues. The aim of this study was to investigate whether,
      and by means of which mechanism, the antiglycation defence Glo1 was involved in
      the apoptosis induced by 0.1 and 1uM nicotine in human primary osteoblasts
      chronically exposed for 11 and 21 days. By using gene overexpression/silencing
      and scavenging/inhibitory agents, we demonstrated that nicotine induces a
      significant intracellular accumulation of hydrogen peroxide (H2O2) that, by
      inhibiting Glo1, drives MG-H1 accumulation/release. MG-H1, in turn, triggers H2O2
      overproduction via receptor for AGEs (RAGE) and, in parallel, an apoptotic
      mitochondrial pathway by inducing Transglutaminase 2 (TG2) downregulation
      dependent NF-kB desensitization. Measurements of H2O2, Glo1 and MG-H1 circulating
      levels in smokers compared with non-smokers or in smokers with osteoporosis
      compared with those without this bone-related disease supported the results
      obtained in vitro. Our findings newly pose the antiglycation enzymatic defense
      Glo1 and MG-H1 among the molecular events involved in nicotine-induced reactive
      oxygen species-mediated osteoblasts apoptosis, a crucial event in smoker-related
      osteoporosis, and suggest novel exposure markers in health surveillance
      programmes related to smokers-associated osteoporosis.

PMID- 29355740
TI  - Role of organic acids in the integration of cellular redox metabolism and
      mediation of redox signalling in photosynthetic tissues of higher plants.
AB  - Organic acids play a crucial role in numerous metabolic processes accompanied by
      transfer of electrons and protons and linked to the reduction/oxidation of major
      redox couples in plant cells, such as NAD, NADP, glutathione, and ascorbate.
      Fluxes through the pathways metabolizing organic acids modulate redox states in
      cell compartments, contribute to generation of reactive oxygen and nitrogen
      species, and mediate signal transduction processes. Organic acid metabolism not
      only functions to equilibrate the redox potential in plant cells but also to
      transfer redox equivalents between cell compartments supporting various metabolic
      processes. The most important role in this transfer belongs to different forms of
      malate dehydrogenase interconverting malate and oxaloacetate or forming pyruvate
      (malic enzymes). During photosynthesis malate serves as a major form of transfer
      of redox equivalents from chloroplasts to the cytosol and other compartments via
      the malate valve. On the other hand, mitochondria, via alterations of their redox
      potential, become a source of citrate that can be transported to the cytosol and
      support biosynthesis of amino acids. Citrate is also an important retrograde
      signalling compound that regulates transcription of several genes including those
      encoding the alternative oxidase. The alternative oxidase, which is activated by
      increased redox potential and by pyruvate, is, in turn, important for the
      maintenance of redox potential in mitochondria. The roles of organic acids in
      establishing redox equilibrium, supporting ionic gradients on membranes,
      acidification of the extracellular medium, and regulation of production of
      reactive oxygen and nitrogen species are discussed.

PMID- 29355741
TI  - Do screws and screw holes affect osteolysis in cementless cups using highly
      crosslinked polyethylene? A 7 to 10-year follow-up case-control study.
AB  - BACKGROUND: The use of screws and the presence of screw holes may cause
      acetabular osteolysis and implant loosening in cementless total hip arthroplasty
      (THA) using conventional polyethylene. In contrast, this issue is not fully
      understood using highly crosslinked polyethylene (HXLPE), particularly in large
      comparative study. Therefore, we performed a case-control study to assess the
      influence of screw usage and screw holes on: (1) implant fixation and osteolysis
      and (2) polyethylene steady-state wear rate, using cases with HXLPE liners
      followed up for 7-10 years postoperatively. HYPOTHESIS: The screw usage and screw
      holes adversely affect the implant fixation and incidence of wear-related
      osteolysis in THA with HXLPE. PATIENTS AND METHODS: We reviewed 209 primary
      cementless THAs performed with 26-mm cobalt-chromium heads on HXLPE liners. To
      compare the effects of the use of screws and the presence of screw holes, the
      following groups were established: (1) with-screw (n=140); (2) without-screw
      (n=69); (3) no-hole (n=27) and (4) group in which a cup with screw holes, but no
      screw was used (n=42). Two adjunct groups (no-hole cups excluded) were
      established to compare the differences in the two types of HXLPE: (5) remelted
      group (n=100) and (6) annealed group (n=82). Implant stability and osteolysis
      were evaluated by plain radiography and computed tomography. The wear rate from 1
      year to the final evaluation was measured using plain X-rays and PolyWare Digital
      software. RESULTS: All cups and stems achieved bony fixation. On CT-scan, no
      acetabular osteolysis was found, but there were 3 cases with a small area of
      femoral osteolysis. The mean steady-state wear rate of each group was (1) 0.031+/
      0.022, (2) 0.033+/-0.035, (3) 0.031+/-0.024, (4) 0.029+/-0.018, (5) 0.030+/-0.018
      and (6) 0.034+/-0.023mm/year, respectively. A comparison of the effects of screw
      usage or screw holes found no significant between-group differences in the
      implant stability, prevalence of osteolysis [no acetabular osteolysis and 3/209
      at femoral side (1.4%)] and steady-state wear rate. DISCUSSION: This study
      suggests that there are no adverse effects on the results of THA with HXLPE from
      the use of cups with screw holes and the use of screws for cup fixation. LEVEL OF
      EVIDENCE: Level III retrospective case-control study.

PMID- 29355742
TI  - Intraarticular synovial sarcoma of the knee rising from a lateral meniscus - a
      case report.
AB  - : Synovial sarcoma (SS) is a rare mesenchymal tumor, accounting less than 10% of
      soft tissue sarcomas. We report a case of intraarticular SS mimicking nodular
      synovitis and lateral meniscus rupture. Due to clinical and radiological
      presentation, arthroscopic synovectomy was performed, and histology confirmed
      nodular synovitis. After four years the lesion recurred and new arthroscopic
      biopsy was performed, revealing a monophasic SS with SYT/SSX1 translocation.
      Repeated histology of the first specimen confirmed appearance of a nodular
      synovitis microscopically, with no morphological criteria for a sarcoma, but
      molecular analysis showed positive SYT/SSX1 translocation. Wide extraarticular
      knee resection and reconstruction with a tumor megaendoprosthesis-allograft
      composite was performed with a negative tumor margins. This case report showed
      that in a case of benign histological appearance, underlying sarcoma is possible
      and could be identified in early stages only with an advanced pathology methods.
      LEVEL OF EVIDENCE: Level IV historical case.

PMID- 29355743
TI  - Usefulness of sonication for diagnosing infection in explanted orthopaedic
      implants.
AB  - BACKGROUND: Orthopaedic implant infection is a rare but serious complication
      whose optimal treatment requires an accurate microbiological diagnosis. The
      objective of this study was to determine whether culturing sonicated explants
      improved sensitivity compared to culturing standard sonicated soft-tissue
      samples. HYPOTHESIS: Cultures of explant sonication fluid are more sensitive than
      cultures of soft-tissue sonication fluid in patients with implant infection.
      METHODS: This single-centre retrospective study included all sonication fluid
      samples from implants explanted in orthopaedic surgery theatres for any reason.
      The microbiological results of the implant sonication fluid cultures were
      compared to those of cultures of sonicated soft-tissue and bone samples taken
      during the same procedure. The primary evaluation criterion was the difference in
      microorganisms recovered from explant sonication fluids versus fluid/tissue
      cultures. RESULTS: The study included 187 explants removed between September 2009
      and June 2015. Of the definite infections, 83% were identified by explant
      sonication, 86% by fluid/tissue cultures, and 91% by both techniques combined.
      Explant sonication recovered causative organisms in 10 patients with definite
      infection but negative fluid/soft tissue cultures. Antibiotic therapy prior to
      explantation was associated with lower sensitivity of explant sonication (57% vs.
      67% for fluid/soft tissue cultures). CONCLUSION: Explant sonication improved the
      diagnosis of infection when combined with fluid/soft tissue cultures. LEVEL OF
      EVIDENCE: IV, retrospective single-centre study.

PMID- 29355744
TI  - Iatrogenic peritonitis following an incident during ablation of a pedicle screw.
AB  - Immediate complications can arise due to faulty implantation of material during
      fusion procedures, but none have been reported in connection with ablation of
      material in the spine. We report a case of intraperitoneal migration of a pedicle
      screw during attempted removal. It crossed the psoas muscle and perforated a
      small-intestine loop, triggering hemorrhagic shock and peritonitis by
      perforation. We analyze the causes and mechanisms underlying this exceptional
      case of migration, with a view to sharing preventive measures. Initial extra
      pedicular screw positioning and the pressure exerted to remove it were
      responsible for this serious incident.

PMID- 29355745
TI  - A rare location for a common tumor: Lingual lipoma.
AB  - Lipomas are the most common benign tumors in human body but their occurrence in
      the oral cavity is very rare. They present as a slow growing, yellowish
      submucosal and painless mass. The treatment consists of a simple surgical
      excision. The histopathologic examination confirms the diagnosis. We present a
      case of tongue lipoma.

PMID- 29355746
TI  - Bone remodelling in vitro: Where are we headed?: -A review on the current
      understanding of physiological bone remodelling and inflammation and the
      strategies for testing biomaterials in vitro.
AB  - Bone remodelling is a dynamic process required for the maintenance of bone
      architecture in response to the changing mechanical needs. It is also a vital
      process during the repair of bone tissue following injury. Clinical intervention
      in terms of autografting or allografting is often required to heal bone injuries
      where physiological healing fails. The use of biomaterials as alternatives to
      autografts and allografts has spurred a significant research interest into
      further development of biomaterials for better clinical outcomes. Unfortunately,
      many biomaterials fail to make it to the clinic or fail after implantation due to
      the inconsistencies observed between in vitro and in vivo studies. It is
      therefore important to mimic the in vivo situation as closely as possible in an
      in vitro setting for testing biomaterials. The current in vitro models focus
      mostly on investigating the behaviour of osteoblast progenitors with the
      biomaterial under development as well as assessing the behaviour of osteoclasts,
      endothelial cells etc. However, the sequence of events that take place during
      bone healing or remodelling are not incorporated into the current in vitro
      models. This review highlights our current understanding of the physiological
      bone remodelling and the bone healing process followed by strategies to
      incorporate both the physiological and pathophysiological events into an in vitro
      environment. Here, we propose three strategies for the assessment of biomaterials
      for bone, which includes; (1) testing biomaterials in the presence of immune
      cells, (2) testing biomaterials for osteogenesis, and (3) testing biomaterials in
      the presence of osteoclasts followed by osteoblasts to recapitulate the
      physiological events of bone resorption prior to bone formation. The focus of
      this review is to discuss the third strategy in details as the first two
      strategies are currently incorporated into a majority of in vitro experiments.

PMID- 29355747
TI  - Proximal Linear Extension of Skin Hypopigmentation After Ultrasound-Guided
      Corticosteroid Injection for de Quervain Tenosynovitis: A Case Presentation.
AB  - : de Quervain tenosynovitis is a stenosing tenosynovitis of the first dorsal
      compartment of the wrist that can lead to painful functional impairment of the
      upper limb. This case presentation describes a rare adverse effect of
      corticosteroid injection (CSI) involving local skin atrophy and hypopigmentation
      with proximal linear extension. In this case, hypopigmentation developed from the
      wrist to beyond the elbow after CSI with ultrasound guidance and targeted
      placement of the injectate in the extensor tendon sheath of the first dorsal
      compartment. Dermal complications of CSI are rare but notable and potentially
      disfiguring events that should be discussed with every patient during the
      informed consent process before soft tissue CSIs. LEVEL OF EVIDENCE: V.

PMID- 29355748
TI  - The potential of clustering methods to define intersection test scenarios:
      Assessing real-life performance of AEB.
AB  - Intersection accidents are frequent and harmful. The accident types 'straight
      crossing path' (SCP), 'left turn across path - oncoming direction' (LTAP/OD), and
      'left-turn across path - lateral direction' (LTAP/LD) represent around 95% of all
      intersection accidents and one-third of all police-reported car-to-car accidents
      in Germany. The European New Car Assessment Program (Euro NCAP) have announced
      that intersection scenarios will be included in their rating from 2020; however,
      how these scenarios are to be tested has not been defined. This study
      investigates whether clustering methods can be used to identify a small number of
      test scenarios sufficiently representative of the accident dataset to evaluate
      Intersection Automated Emergency Braking (AEB). Data from the German In-Depth
      Accident Study (GIDAS) and the GIDAS-based Pre-Crash Matrix (PCM) from 1999 to
      2016, containing 784 SCP and 453 LTAP/OD accidents, were analyzed with principal
      component methods to identify variables that account for the relevant total
      variances of the sample. Three different methods for data clustering were applied
      to each of the accident types, two similarity-based approaches, namely
      Hierarchical Clustering (HC) and Partitioning Around Medoids (PAM), and the
      probability-based Latent Class Clustering (LCC). The optimum number of clusters
      was derived for HC and PAM with the silhouette method. The PAM algorithm was both
      initiated with random start medoid selection and medoids from HC. For LCC, the
      Bayesian Information Criterion (BIC) was used to determine the optimal number of
      clusters. Test scenarios were defined from optimal cluster medoids weighted by
      their real-life representation in GIDAS. The set of variables for clustering was
      further varied to investigate the influence of variable type and character. We
      quantified how accurately each cluster variation represents real-life AEB
      performance using pre-crash simulations with PCM data and a generic algorithm for
      AEB intervention. The usage of different sets of clustering variables resulted in
      substantially different numbers of clusters. The stability of the resulting
      clusters increased with prioritization of categorical over continuous variables.
      For each different set of cluster variables, a strong in-cluster variance of
      avoided versus non-avoided accidents for the specified Intersection AEB was
      present. The medoids did not predict the most common Intersection AEB behavior in
      each cluster. Despite thorough analysis using various cluster methods and
      variable sets, it was impossible to reduce the diversity of intersection
      accidents into a set of test scenarios without compromising the ability to
      predict real-life performance of Intersection AEB. Although this does not imply
      that other methods cannot succeed, it was observed that small changes in the
      definition of a scenario resulted in a different avoidance outcome. Therefore, we
      suggest using limited physical testing to validate more extensive virtual
      simulations to evaluate vehicle safety.

PMID- 29355749
TI  - Discovery of a highly active anticancer analogue of cardamonin that acts as an
      inducer of caspase-dependent apoptosis and modulator of the mTOR pathway.
AB  - Cardamonin is a natural chalcone that has been shown to exhibit high anticancer
      activity. In an attempt to discover analogues of cardamonin with enhanced
      anticancer activity, 19 analogues were synthesized and tested against A549 and
      HK1 cell lines. Results of the MTS cell viability assay showed that several
      derivatives possessed cytotoxic activities that were several-fold more potent
      than cardamonin. SAR analysis showed the importance of the ketone and alkene
      groups for bioactivity, while substituting cardamonin's phenolic groups with more
      polar moieties resulted in activity enhancement. As part of the SAR study and
      further exploration of chemical space, the effect of metal coordination on
      cytotoxicity was also investigated, but it was only possible to successfully
      obtain the Cu (II) complex of cardamonin (19). Compound 19 was the most active
      analogue possessing IC50 values of 13.2MUM and 0.7MUM against A549 and HK1 cells,
      corresponding to a 5- and 32-fold increase in activity, respectively. It was also
      able to significantly inhibit the migration of A549 and HK1 cells. Further mode
      of action studies have shown that the most active analogue, 19, induced DNA
      damage resulting in G2/M-phase cell- cycle arrest in both cell lines. These
      events further led to the induction of apoptosis by the compound via caspase-3/7
      and caspase-9 activation, PARP cleavage and downregulation of Mcl-1 expression.
      Moreover, 19 inhibited the expression levels of p-mTOR and p-4EBP1, which
      indicated that it exerted its anticancer activity, at least in part, via
      inhibition of the mTOR signalling pathway.

PMID- 29355750
TI  - Racemic indole alkaloids from the seeds of Peganum harmala.
AB  - Five pairs of new 2-oxoindole alkaloids, (+/-)-peganumalines A-E (1-5), and a new
      indole alkaloid, peganumaline F (6), along with two known analogues, were
      isolated from the seeds of Peganum harmala. Their structures and absolute
      configurations were elucidated through spectroscopic analyses and quantum
      chemistry calculations. Notably, (+/-)-peganumalines A (1) represent a pair of
      rare 2-oxoindole dimeric alkaloid enantiomer with the hitherto unknown carbon
      skeleton. All isolates were tested for antiproliferative and antibacterial
      activities.

PMID- 29355751
TI  - 7alpha,8alpha-Epoxynagilactones and their glucosides from the twigs of Podocarpus
      nagi: Isolation, structures, and cytotoxic activities.
AB  - A phytochemical investigation of twigs of Podocarpus nagi resulted in the
      identification of eight new type B nagilactones (1-8), all bearing a
      7alpha,8alpha-epoxy-9(11)-enolide substructure, along with two known analogs (9
      10). Their structures were determined on the basis of spectroscopic analysis,
      including HRESIMS, IR and NMR experiments, and X-ray crystallographic analysis.
      In vitro cytotoxic assay exhibited that compounds 1, 2, 9 and 10 could induce
      antiproliferation against three different types of human cancer cells while
      compounds 3 and 5 were inactive. Notably, the IC50 value of compound 1 is
      0.208MUM for A431 human epidermoid carcinoma cells, reaching the same level as
      the positive control combretastatin A-4 (0.104MUM). Furthermore, compound 1
      performed a strong inhibition of cancer cells by triggering apoptosis and
      arresting the cell cycle at G1 phase. These results unfold potential anticancer
      therapeutic applications of type B nagilactones.

PMID- 29355752
TI  - Binding of vanadium to human serum transferrin - voltammetric and spectrometric
      studies.
AB  - Previous studies generally agree that in the blood serum vanadium is transported
      mainly by human serum transferrin (hTF). In this work through the combined use of
      electrochemical techniques, matrix-assisted laser desorption/ionization time of
      flight (MALDI-TOF) mass spectrometry and small-angle X-ray scattering (SAXS) data
      it is confirmed that both VIV and VV bind to apo-hTF and holo-hTF. The
      electrochemical behavior of solutions containing vanadate(V) solutions at pH=7.0,
      analyzed by using two different voltammetric techniques, with different time
      windows, at a mercury electrode, Differential Pulse Polarography (DPP) and Cyclic
      Voltammetry (CV), is consistent with a stepwise reduction of VV->VIV and VIV
      >VII. Globally the voltammetric data are consistent with the formation of 2:1
      complexes in the case of the system VV-apo-hTF and both 1:1 and 2:1 complexes in
      the case of VV-holo-hTF; the corresponding conditional formation constants were
      estimated. MALDI-TOF mass spectrometric data carried out with samples of VIVOSO4
      and apo-hTF and of NH4VVO3 with both apo-hTF and holo-hTF with V:hTF ratios of
      3:1 are consistent with the binding of vanadium to the proteins. Additionally the
      SAXS data suggest that both VIVOSO4 and NaVVO3 can effectively interact with
      human apo-transferrin, but for holo-hTF no clear evidence was obtained supporting
      the existence or the absence of protein-ligand interactions. This latter data
      suggest that the conformation of holo-hTF does not change in the presence of
      either VIVOSO4 or NH4VVO3. Therefore, it is anticipated that VIV or VV bound to
      holo-hTF may be efficiently up-taken by the cells through receptor-mediated
      endocytosis of hTF.

PMID- 29355753
TI  - Cortisol and melatonin in the cutaneous stress response system of fish.
AB  - The stress hormone cortisol, together with antioxidants, melatonin (Mel) and its
      biologically active metabolites, 5-methoxykynuramines, including AFMK, set up a
      local stress response system in mammalian skin. Our in vitro study of the
      European flounder (Platichthys flesus) was designed to examine whether Mel and
      AFMK would respond to cortisol while a glucocorticoid is added to the incubation
      medium. The concentrations of cortisol in the incubation medium mimic plasma
      cortisol levels seen in fish exposed to different types of stresses such as
      handling, confinement, high density, food-deprivation or air-exposure. We
      measured Mel and AFMK in skin explants and culture media using high-performance
      liquid chromatography (HPLC) with fluorescence detection. We also analysed
      melanosome response (dispersion/aggregation) in the explants subjected to the
      different treatments. Cortisol stimulated the release of Mel and AFMK from skin
      explants in a dose-dependent manner. Melanosome dispersion and a darkening of the
      skin explants were observed after incubation with cortisol. This study is the
      first to demonstrate the interrelationship between cortisol and Mel/AFMK in fish
      skin. Our data strongly suggest that the cutaneous stress response system (CSRS)
      is present in fish. The question remains whether Mel, AFMK or cortisol are
      synthetized locally in fish skin and/or transported by the bloodstream. The
      presence of the CSRS should be taken into account during elaboration of new
      indicators of fish welfare both in aquaculture and in the wild.

PMID- 29355754
TI  - Blocking mutation independent p53 aggregation by emodin modulates autophagic cell
      death pathway in lung cancer.
AB  - Loss of p53 function via mutation is a very common cause of human cancers. Recent
      studies have provided evidence on presence of self aggregated p53 in cancer cells
      leading to its altered functions towards cause of cancer. The general notion has
      been that mutated p53 exposes adhesive sites that promote self aggregation,
      however a complete mechanistic understanding to this has been lacking. We
      embarked on the present study towards exploring the differential aggregation
      pattern in cells expressing mutated TP53 (HaCaT keratinocytes) vs those
      expressing the wild type copy of the p53 protein (A549 lung cancer cell line).
      The studies led us to interesting observation that formation of p53 protein
      aggregates is not always associated with TP53 mutation. The A549 lung cancer
      cells, having wild type TP53, showed the appearance of p53 protein aggregates,
      while no protein aggregates were observed in normal HaCaT keratinocytes carrying
      mutant TP53. We went on to study the effect of blocking protein aggregation by
      emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) and figured that inhibiting p53
      protein aggregation can elevate the level of autophagy in A549 lung cancer cell
      line while there is no significant effect on autophagy in normal non-cancerous
      HaCaT cells. Moreover, ATG5 was found to be coaggregated with p53 aggregates
      which dissociated after emodin treatment, indicating further induction of
      autophagy in A549 cells only. From these observations, we conclude that the
      increased level of autophagy might be the mechanism for the removal of p53
      protein aggregates which restores p53 function in A549 cells after emodin
      treatment .This encourages further studies towards deciphering related
      mechanistic aspects vis-a-vis potential therapeutic strategies against cancer.

PMID- 29355755
TI  - Two-pore channels mediated receptor-operated Ca2+ entry in pulmonary artery
      smooth muscle cells in response to hypoxia.
AB  - The aim of this study was to investigate the influence of two-pore channels
      mediated receptor-operated Ca2+ entry on pulmonary arterial smooth muscle cell
      (PASMC) under hypoxia conditions. PASMCs were separated using the direct adherent
      culture method. The cultured cells were observed under optic microscope and the
      phenotypes of cells were identified by immunohistochemistry. The expression of
      NAADP was examined by ELISA. CaN, TPC1, TPC2 and NFATc3 protein levels were
      examined using Western blotting. Real-time PCR was utilized to detect the level
      of TPC1 and TPC2 mRNA. Fluorescent probe technique was used to explore the
      [Ca2+]i in PASMCs. Proliferation and migration of PASMCs were examined by MTT
      assay and Transwell, respectively. The results showed that cells displayed a
      typical "peak-valley" growth pattern and positive for alpha-actin staining.
      Expression of NAADP, CaN, NFATc3, TPC1 and TPC2 under PASMCs exposed to hypoxia
      after 24 h and 48 h were higher than control, however, cells treated with Ned-19
      were significantly decreased compared with control. Levels of CaN and NFATc3
      protein collected from RPASMCs transfected with TPCs siRNA were observably
      decreased than scrambled siRNA. Under hypoxia condition for 12 h, 24 h and 48 h,
      TPC1 and TPC2 mRNA levels were higher in PASMCs compared as control. The [Ca2+]i
      evoked by hypoxia significantly increased than normoxia group. Nevertheless, the
      [Ca2+]i of the groups treated with Ned-19 and transfected with TPCs siRNA were
      markedly lower compared with control. In conclusion, the TPCs influence on
      function of pulmonary artery smooth muscle cells by mediated Ca2+ Signals under
      hypoxia condition.

PMID- 29355756
TI  - GLA supplementation regulates PHD2 mediated hypoxia and mitochondrial apoptosis
      in DMBA induced mammary gland carcinoma.
AB  - The aim of the present study is to evaluate the effect of gamma linolenic acid
      (GLA) on mitochondrial mediated death apoptosis, hypoxic microenvironment and
      cholinergic anti-inflammatory pathway against 7, 12-dimethylbenz (a) anthracene
      (DMBA) induced mammary gland carcinoma. The effects of GLA were evaluated
      morphologically and biochemically against DMBA induced mammary gland carcinoma.
      The metabolic study was done for evaluation of biomarkers using 1H NMR. The
      present study was also verified through immunoblotting and qRT-PCR studies for
      the evaluation of various pathways. GLA treatment has a delineate implementation
      upon morphology of the tissues when evaluated through carmine staining,
      hematoxyline and eosin staining and scanning electron microscopy. GLA also
      demarked a commendatory proclamation of the fifteen key serum metabolites
      analogous with amino acid metabolism and fatty acid metabolism when recognized
      through1H NMR studies. The immunoblotting and qRT-PCR studies accomplished that
      GLA mediated mitochondrial death apoptosis, curtail hypoxic microenvironment
      along with hindrance of de novo fatty acid synthesis and also mediate the
      cholinergic anti-inflammatory pathway to proclaim its anticancer effects.

PMID- 29355757
TI  - Non-genomic mechanisms of protein phosphatase 2A (PP2A) regulation in cancer.
AB  - Propagation of transient signals requires coordinated suppression of antagonistic
      phosphatase activity. Protein phosphatase 2A (PP2A) is a broad specificity
      serine/threonine phosphatase that functions as an antagonist of many signaling
      pathways associated with growth and proliferation, and endogenous inhibitory
      mechanisms suppress PP2A activity in response to mitogenic stimuli. These
      inhibitory mechanisms, including expression and activation of endogenous
      inhibitor proteins and phosphoregulation of PP2A subunits, are also engaged by
      aberrant constitutive activation of mitogenic pathways in cancer. Inhibition of
      PP2A activity has been shown to promote malignant transformation and endogenous
      inhibitory mechanisms of PP2A have been associated with malignant progression and
      prognosis in a wide range of cancers. Despite existence of recurrent mutations
      and other genetic and gene regulatory alterationsin PP2A genes, they collectively
      appear at relatively low frequency, and in only some cancer types. The non
      genomic inhibition of PP2A activity by increased expression of endogenous PP2A
      inhibitor proteins greatly exceeds the frequency of genetic mutations of PP2A
      genes in human cancers. This feature makes PP2A an untypical tumor suppressor,
      and may have influenced its recognition as one of the critical human cell
      transformation mechanisms. We propose that non-genetic inhibition is the dominant
      mechanism causing loss of PP2A tumor suppressor function in cancer cells,
      possibly because these mechanisms do not elicit genomic instability associated
      with genetic loss of function of specific PP2A subunits.

PMID- 29355758
TI  - Identification and molecular characterization of the Pim1 serine/threonine kinase
      homolog in Litopenaeus vannamei.
AB  - The Pim1 serine/threonine kinase is associated with multiple cellular functions
      including proliferation, survival, differentiation, apoptosis, tumorigenesis,
      immune regulation and inflammation in vertebrates. However, little is known about
      the role of Pim1 in invertebrate immunity. In this study, we identified and
      characterized for the first time, a Pim1 (LvPim1) gene in Litopenaeus vannamei,
      with a full-length cDNA of 2352 bp and a 1119 bp open reading frame (ORF)
      encoding a putative protein of 372 amino acids, which contains a typical
      serine/threonine kinase domain. Sequence and phylogenetic analysis revealed that
      LvPim1 shared a close evolutionary relationship with Pim1 from vertebrates. Real
      time qPCR analysis showed that LvPim1 was widely expressed in all tissues tested;
      with its transcript level induced in hepatopancreas and hemocytes upon challenge
      with Vibrio parahaemolyticus, Streptoccocus iniae, lipopolysaccharide (LPS), and
      white spot syndrome virus (WSSV), thus, suggesting its probable involvement in
      shrimp immune response. Moreover, knockdown of LvPim1 resulted in increased
      hemocytes apoptosis; shown by high caspase3/7 activity, coupled with increase in
      pro-apoptotic LvCaspase3 and LvCytochrome C, and decrease in pro-survival LvBcl2,
      LvIAP1, and LvIAP2 mRNA expression in hemocytes. Finally, LvPim1 knockdown
      renders shrimps more susceptible to V. parahaemolyticus infection. Taken
      together, our present data strongly suggest that LvPim1 is involved in modulating
      shrimp resistance to pathogen infection, promote hemocytes survival, and
      therefore plays a role in shrimp immune response.

PMID- 29355759
TI  - Novel subunit vaccine with linear array epitope protect giant grouper against
      nervous necrosis virus infection.
AB  - Viral nervous necrosis caused by nervous necrosis virus (NNV) is one of the most
      severe diseases resulting in high fish mortality rates and high economic losses
      in the giant grouper industry. Various NNV vaccines have been evaluated, such as
      inactivated viruses, virus-like particles (VLPs), recombinant coat proteins,
      synthetic peptides of coat proteins, and DNA vaccines. However, a cheaper
      manufacturing process and effective protection of NNV vaccines for commercial
      application are yet to be established. Hence, the present study developed a novel
      subunit vaccine composed of a carrier protein, receptor-binding domain of
      Pseudomonas exotoxin A, and tandem-repeated NNV coat protein epitopes by using
      the structural basis of epitope prediction and the linear array epitope (LAE)
      technique. On the basis of the crystal structure of the NNV coat protein, the
      epitope was predicted from the putative target cell receptor-binding region to
      elicit neutralizing immune responses. The safety of the LAE vaccine was
      evaluated, and all vaccinated fish survived without any physiological changes.
      The coat protein-specific antibody titers in the vaccinated fish increased after
      vaccine administration and exerted NNV-neutralizing effects. The efficacy tests
      revealed that the relative percent survival (RPS) of LAE antigen formulated with
      adjuvant was above 72% and LAE vaccine was effective for preventing NNV infection
      in giant grouper. This study is the first to develop an NNV vaccine by using
      epitope repeats, which provided effective protection to giant grouper against
      virus infection. The LAE construct can be used as a vaccine design platform
      against various pathogenic diseases.

PMID- 29355760
TI  - Molecular cloning and characterization of FADD from the orange-spotted grouper
      (Epinephelus coioides).
AB  - Fas-associated protein with death domain (FADD) is the key adaptor protein that
      transmits apoptotic signals mediated by the main death receptors. Besides being
      an essential instrument in cell death, FADD is also implicated in proliferation,
      cell cycle progression, tumor development, inflammation, innate immunity, and
      autophagy. In the present study, a FADD homologue (EcFADD) from the orange
      spotted grouper (Epinephelus coioides) was cloned and its possible role in fish
      immunity was analyzed. The full length cDNA of EcFADD contains 808 base pairs
      (bp), including a 573 bp open reading frame that encodes a 190 amino acid protein
      with a predicted molecular mass of 21.81 kDa. Quantitative real-time polymerase
      chain reaction analysis indicated that EcFADD was distributed in all examined
      tissues. The expression of EcFADD in the spleen of E. coioides was differentially
      up-regulated when challenged with Singapore grouper iridovirus (SGIV) or
      polyinosine-polycytidylic acid(poly[I:C]). EcFADD was abundantly distributed in
      both the cytoplasm and nucleus in grouper spleen (GS) and fathead minnow (FHM)
      epithelial cells. Over-expression of EcFADD inhibited SGIV infection and
      replication and SGIV-induced apoptosis. To achieve antiviral and anti-apoptosis
      activities, FADD promoted the activation of interferon-stimulated response
      element (ISRE) and type I interferon (IFN) genes in the antiviral IFN signaling
      pathway and inhibited activation of apoptosis-related transcription factors p53.
      Our results not only characterize FADD but also reveal new immune functions and
      the molecular mechanisms by which FADD responds to virus infection and virus
      induced apoptosis.

PMID- 29355761
TI  - Effects of dietary Spirulina platensis on growth performance, hematological and
      serum biochemical parameters, hepatic antioxidant status, immune responses and
      disease resistance of Coral trout Plectropomus leopardus (Lacepede, 1802).
AB  - The present study investigated the effects of dietary Spirulina platensis
      supplementation on growth performance, hematological and serum biochemical
      parameters, hepatic antioxidant status, immune responses and resistance to the
      pathogen infection in Coral trout Plectropomus leopardus. The fish were fed for 8
      week with diets containing different levels of S. platensis: 0% (C), 2% (SP2), 4%
      (SP4), 6% (SP6), 8% (SP8) and 10% (SP10) as treatment groups, followed by a
      Vibrio harveyi infection test for 14 d. The study indicated that dietary
      supplementation with Spirulina platensis could significantly improve growth
      performance, and the highest weight gain rate (WGR) and specific growth rate
      (SGR) were observed in group SP10 (P < .05). Red cell count (RBC), white cell
      count (WBC), hemoglobin (Hb) and total antioxidant capacity (T-AOC) in the S.
      platensis supplemented groups were significantly higher than those of group C (P
      < .05). However, the levels of cholesterol, triglyceride and malondialdehyde
      (MDA) contents, and superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPX) activities decreased with the increasing of dietary S. platensis
      levels. Compared with group C, the lysozyme (LYZ) and respiratory burst
      activities (RBA), and immunoglobulin (Ig) and complement contents in group SP4,
      SP6, SP8 and SP10 increased significantly than those of group C respectively (P <
      .05). After challenge with V. harveyi, the survival rate in group SP4, SP6, SP8
      and SP10 was significantly higher than that of group C, and the highest survival
      rate was in group SP10 (P < .05). These results indicated that P. leopardus fed a
      diet supplemented with S. platensis (especially at 10%) could significantly
      promote its growth performance, improve its hepatic antioxidant status, and
      enhance its immune ability and resistance to V. harveyi infection.

PMID- 29355763
TI  - Transcriptomic analysis of exosomal shuttle mRNA in Pacific oyster Crassostrea
      gigas during bacterial stimulation.
AB  - As marine invertebrates, oysters lack adaptive immunity and employ innate
      immunity as the front line and almost the solo defense mechanism to protect them
      against invaders. Accumulating research achievements demonstrated that exosomes
      could act as innate immune effectors that contribute to host defense mechanism.
      To better understand the immune functions of exosomes in Crassostrea gigas
      against bacterial stimulation, RNA-Seq was applied to explore the global
      expression changes of exosomes in oyster after Staphylococcus aureus and Vibrio
      splendidus stimulation. Totally 171573691 single end raw reads were yielded via
      Ion Torrent Proton sequencing, which were trimmed into 121988325 clean reads, and
      then 1505 abundant exosomal shuttle mRNAs (esmRNAs) were identified. Gene
      ontology (GO) analysis revealed that these abundant esmRNAs could be categorized
      into 15 cellular components, 12 molecular functions and 21 biological processes,
      and these abundant esmRNAs were mapped onto 62 biological signaling pathways by
      KEGG. In total, 68 significant differentially expressed genes (DEGs, Fold change
      >= 2, Q-value < 0.05) were identified between S. aureus stimulated group and
      control group, including 21 up-regulated and 47 down-regulated ones. While 99
      significant DEGs between V. splendidus challenged group and control group were
      identified, including 42 up-regulated and 57 down-regulated ones. To validate the
      transcriptomic data, 24 DEGs were randomly selected and confirmed via
      quantitative real-time PCR (qRT-PCR) and the results showed that their expression
      patterns agreed well with the RNA-Seq analysis. This study would enrich the C.
      gigas transcriptome database and provide insight into the immune functions of
      oyster exosomes against bacterial infection.

PMID- 29355762
TI  - A comparative study of three akirin genes from big belly seahorse Hippocampus
      abdominalis: Molecular, transcriptional and functional characterization.
AB  - Akirins, members of the NF-kappaB signaling pathway, are highly conserved nuclear
      proteins, which regulate gene expression in many physiological processes,
      including immunity, myogenesis, carcinogenesis, and embryogenesis. The akirin
      family in teleost fish consists of two to three genes. In the present study,
      three akirin genes from Hippocampus abdominalis were identified from a
      transcriptome database and designated as HaAkirin1, HaAkirin2(1), and
      HaAkirin2(2). The nuclear localization of HaAkirin1 and HaAkirin2(1) was
      confirmed by subcellular localization analysis. In contrast, diffused
      localization of HaAkirin2(2) was identified in the nucleus and cytoplasm that
      confirmed the aberrant nature of the nuclear localization signal. Phylogenetic
      analysis revealed a closer relationship of HaAkirins with other known teleost
      akirins. All three HaAkirin transcripts were ubiquitously expressed in all
      examined tissues with higher expression in ovary tissue. Immune challenge with
      LPS, poly I:C, and Streptococcus iniae exhibited a significant increase in the
      expression of all three HaAkirins in kidney and liver tissues. NF-kappaB
      luciferase assays revealed that relative luciferase activity was significantly
      higher for all three HaAkirin genes than mock controls. These results suggest
      that HaAkirin genes might play a role in regulating NF-kappaB dependent immune
      gene expression and their expression could be induced by bacterial and viral
      pathogen recognition molecular patterns.

PMID- 29355764
TI  - Complement component Bf/C2b gene mediates immune responses against Aeromonas
      hydrophila in grass carp Ctenopharyngodon idella.
AB  - The complement system is a significant component of innate immunity. Here, we
      identified a Bf/C2 homolog (gcBf/C2b) in grass carp. gcBf/C2b shares a high
      similarity with Bf/C2b counterparts in other teleosts. gcBf/C2b transcription was
      widely distributed in different tissues, induced by Aeromonas hydrophila in vivo
      and in vitro, and affected by lipopolysaccharide and flagellin stimulation in
      vitro. In cells over-expressing gcBf/C2b, transcript levels of all components
      except gcC5 were significantly enhanced, and gcBf/C2b, gcIL1beta, gcTNF-alpha,
      gcIFN, gcCD59, gcC5aR1, and gcITGbeta-2 were significantly upregulated after A.
      hydrophila challenge or stimulation with bacterial pathogen-associated molecular
      patterns (PAMPs). However, gcBf/C2b in interference cells down-regulated the
      transcript levels after A. hydrophila challenge, and gcBf/C2b induced NF-kappaB
      signaling. These findings indicate the vital role of gcBf/C2b in innate immunity
      in grass carp.

PMID- 29355765
TI  - Transcranial alternating current stimulation with speech envelopes modulates
      speech comprehension.
AB  - Cortical entrainment of the auditory cortex to the broadband temporal envelope of
      a speech signal is crucial for speech comprehension. Entrainment results in
      phases of high and low neural excitability, which structure and decode the
      incoming speech signal. Entrainment to speech is strongest in the theta frequency
      range (4-8 Hz), the average frequency of the speech envelope. If a speech signal
      is degraded, entrainment to the speech envelope is weaker and speech
      intelligibility declines. Besides perceptually evoked cortical entrainment,
      transcranial alternating current stimulation (tACS) entrains neural oscillations
      by applying an electric signal to the brain. Accordingly, tACS-induced
      entrainment in auditory cortex has been shown to improve auditory perception. The
      aim of the current study was to modulate speech intelligibility externally by
      means of tACS such that the electric current corresponds to the envelope of the
      presented speech stream (i.e., envelope-tACS). Participants performed the
      Oldenburg sentence test with sentences presented in noise in combination with
      envelope-tACS. Critically, tACS was induced at time lags of 0-250 ms in 50-ms
      steps relative to sentence onset (auditory stimuli were simultaneous to or
      preceded tACS). We performed single-subject sinusoidal, linear, and quadratic
      fits to the sentence comprehension performance across the time lags. We could
      show that the sinusoidal fit described the modulation of sentence comprehension
      best. Importantly, the average frequency of the sinusoidal fit was 5.12 Hz,
      corresponding to the peaks of the amplitude spectrum of the stimulated envelopes.
      This finding was supported by a significant 5-Hz peak in the average power
      spectrum of individual performance time series. Altogether, envelope-tACS
      modulates intelligibility of speech in noise, presumably by enhancing and
      disrupting (time lag with in- or out-of-phase stimulation, respectively) cortical
      entrainment to the speech envelope in auditory cortex.

PMID- 29355766
TI  - Reference ability neural networks and behavioral performance across the adult
      life span.
AB  - To better understand the impact of aging, along with other demographic and brain
      health variables, on the neural networks that support different aspects of
      cognitive performance, we applied a brute-force search technique based on
      Principal Components Analysis to derive 4 corresponding spatial covariance
      patterns (termed Reference Ability Neural Networks -RANNs) from a large sample of
      participants across the age range. 255 clinically healthy, community-dwelling
      adults, aged 20-77, underwent fMRI while performing 12 tasks, 3 tasks for each of
      the following cognitive reference abilities: Episodic Memory, Reasoning,
      Perceptual Speed, and Vocabulary. The derived RANNs (1) showed selective
      activation to their specific cognitive domain and (2) correlated with behavioral
      performance. Quasi out-of-sample replication with Monte-Carlo 5-fold cross
      validation was built into our approach, and all patterns indicated their
      corresponding reference ability and predicted performance in held-out data to a
      degree significantly greater than chance level. RANN-pattern expression for
      Episodic Memory, Reasoning and Vocabulary were associated selectively with age,
      while the pattern for Perceptual Speed showed no such age-related influences. For
      each participant we also looked at residual activity unaccounted for by the RANN
      pattern derived for the cognitive reference ability. Higher residual activity was
      associated with poorer brain-structural health and older age, but -apart from
      Vocabulary-not with cognitive performance, indicating that older participants
      with worse brain-structural health might recruit alternative neural resources to
      maintain performance levels.

PMID- 29355768
TI  - Idiosyncratic organization of cortical networks in autism spectrum disorder.
AB  - Neuroimaging studies of Autism Spectrum Disorder (ASD) have yielded inconsistent
      results indicating either increases or decreases in functional connectivity, or
      both. Recent findings suggest that these seemingly divergent results might be
      underpinned by greater inter-individual variability in brain network connectivity
      in ASD. We tested the hypothesis that the spatial patterns of intrinsic
      connectivity networks (ICNs) are more idiosyncratic in ASD, and demonstrated that
      this increased variability is associated with symptomatology. We estimated whole
      brain functional connectivity based on resting state functional magnetic
      resonance imaging (fMRI) data obtained from the Autism Brain Imaging Data
      Exchange I & II (ABIDE I & II) repository: 422 (69 females) participants with ASD
      and 424 (59 females) typically developing (TD) participants between 6 and 30
      years of age. We clustered individuals' patterns of resting state functional
      connectivity into seven networks, each representing an ICN, and assessed the
      heterogeneity of each vertex on the cortical surface across individuals in terms
      of its incorporation into a particular ICN. We found that the incorporation of
      individual anatomical locations (vertices) to a common network was less
      consistent across individuals in ASD, indicating a more idiosyncratic
      organization of ICNs in the ASD brain. This spatial shifting effect was
      particularly pronounced in the Sensory-Motor Network (SMN) and the Default Mode
      Network (DMN). We also found that this idiosyncrasy in large-scale brain network
      organization was correlated with ASD symptomatology (ADOS). These results support
      the view that idiosyncratic functional connectivity is a hallmark of the ASD
      brain. We provide the first evidence that the anatomical organization of ICNs is
      idiosyncratic in ASD, as well as providing evidence that such abnormalities in
      brain network organization may contribute to the symptoms of ASD.

PMID- 29355767
TI  - Co-activation patterns in resting-state fMRI signals.
AB  - The brain is a complex system that integrates and processes information across
      multiple time scales by dynamically coordinating activities over brain regions
      and circuits. Correlations in resting-state functional magnetic resonance imaging
      (rsfMRI) signals have been widely used to infer functional connectivity of the
      brain, providing a metric of functional associations that reflects a temporal
      average over an entire scan (typically several minutes or longer). Not until
      recently was the study of dynamic brain interactions at much shorter time scales
      (seconds to minutes) considered for inference of functional connectivity. One
      method proposed for this objective seeks to identify and extract recurring co
      activation patterns (CAPs) that represent instantaneous brain configurations at
      single time points. Here, we review the development and recent advancement of CAP
      methodology and other closely related approaches, as well as their applications
      and associated findings. We also discuss the potential neural origins and
      behavioral relevance of CAPs, along with methodological issues and future
      research directions in the analysis of fMRI co-activation patterns.

PMID- 29355769
TI  - Mapping population-based structural connectomes.
AB  - Advances in understanding the structural connectomes of human brain require
      improved approaches for the construction, comparison and integration of high
      dimensional whole-brain tractography data from a large number of individuals.
      This article develops a population-based structural connectome (PSC) mapping
      framework to address these challenges. PSC simultaneously characterizes a large
      number of white matter bundles within and across different subjects by
      registering different subjects' brains based on coarse cortical parcellations,
      compressing the bundles of each connection, and extracting novel connection
      weights. A robust tractography algorithm and streamline post-processing
      techniques, including dilation of gray matter regions, streamline cutting, and
      outlier streamline removal are applied to improve the robustness of the extracted
      structural connectomes. The developed PSC framework can be used to reproducibly
      extract binary networks, weighted networks and streamline-based brain
      connectomes. We apply the PSC to Human Connectome Project data to illustrate its
      application in characterizing normal variations and heritability of structural
      connectomes in healthy subjects.

PMID- 29355771
TI  - Evaluation of kenaf fibers as moving bed biofilm carriers in algal membrane
      photobioreactor.
AB  - In this lab-scale study, the feasibility of using kenaf fibers as moving bed
      biofilm carriers in hybrid microalgal membrane photobioreactors (HMPBR) in
      organic matter and atrazine elimination from real secondary effluent was
      evaluated. For evaluating the kinetics of biofilm substrate consumption, an
      experimental model was proposed. Inoculation of wastewater samples with free
      carriers resulted in the greater removal of target pollutants. Removal efficiency
      of atrazine and chemical oxygen demand (COD) increased to 27% and 16%, with
      respect to the control, respectively. The total biomass accumulation in HMPBR
      exceeded 5g/L, and the microalgae tended to aggregate and attached to biofilm
      carriers. The removal efficiency of HMPBR improved significantly via inoculation
      of kenaf fiber carriers with bioremediation microalgal strains (p < 0.01). A
      lower stabilization ratio (VSS/TSS) was also recorded. The biomass in HMPBR
      included more lipids and carbohydrates. The results revealed that kenaf fibers
      could improve and upgrade the biological activity of different wastewater
      treatment applications, considering the great potential of biofilm carriers and
      their effluent quality.

PMID- 29355772
TI  - Maize straw decorated with sulfide for tylosin removal from the water.
AB  - MS-ZnS and MS-ZnS:Mn complexes were synthesized via a simple method. The results
      showed that sulfide was successfully loaded on the maize straw. The results of
      fitting the experimental data showed that the sorption conforms to the pseudo
      second-order kinetics, and the TYL sorption on MS fit the Henry model well, but
      the Freundlich model was more suited to MS-ZnS and MS-ZnS:Mn. In addition, the kf
      values of MS-ZnS (206.0(mg/kg)/(mg/L)n) and MS-ZnS:Mn (382.5(mg/kg)/(mg/L)n) were
      significantly greater than that of MS (72.2(mg/kg)/(mg/L)n), indicating that ZnS
      and ZnS:Mn could improve the sorption capacity of TYL on MS. The pH, ionic
      strength and temperature influence the sorption process, and the sorption ability
      of TYL on MS-ZnS and MS-ZnS:Mn showed little change when the solution pH was > 5;
      the amount of TYL sorption on the adsorbents gradually decreased with the
      increasing concentration of KNO3. Electrostatic interactions, H bonding and
      hydrophobic interactions are involved in the sorption of TYL on MS, MS-ZnS and MS
      ZnS:Mn, and compared with MS, the main mechanism is surface complexation. This
      research can provide technical support for the utilization of biomass and the
      restoration of water polluted by antibiotics.

PMID- 29355770
TI  - Incorporating spatial constraint in co-activation pattern analysis to explore the
      dynamics of resting-state networks: An application to Parkinson's disease.
AB  - The dynamics of the brain's intrinsic networks have been recently studied using
      co-activation pattern (CAP) analysis. The CAP method relies on few model
      assumptions and CAP-based measurements provide quantitative information of
      network temporal dynamics. One limitation of existing CAP-related methods is that
      the computed CAPs share considerable spatial overlap that may or may not be
      functionally distinct relative to specific network dynamics. To more accurately
      describe network dynamics with spatially distinct CAPs, and to compare network
      dynamics between different populations, a novel data-driven CAP group analysis
      method is proposed in this study. In the proposed method, a dominant-CAP (d-CAP)
      set is synthesized across CAPs from multiple clustering runs for each group with
      the constraint of low spatial similarities among d-CAPs. Alternating d-CAPs with
      less overlapping spatial patterns can better capture overall network dynamics.
      The number of d-CAPs, the temporal fraction and spatial consistency of each d
      CAP, and the subject-specific switching probability among all d-CAPs are then
      calculated for each group and used to compare network dynamics between groups.
      The spatial dissimilarities among d-CAPs computed with the proposed method were
      first demonstrated using simulated data. High consistency between simulated
      ground-truth and computed d-CAPs was achieved, and detailed comparisons between
      the proposed method and existing CAP-based methods were conducted using simulated
      data. In an effort to physiologically validate the proposed technique and
      investigate network dynamics in a relevant brain network disorder, the proposed
      method was then applied to data from the Parkinson's Progression Markers
      Initiative (PPMI) database to compare the network dynamics in Parkinson's disease
      (PD) and normal control (NC) groups. Fewer d-CAPs, skewed distribution of
      temporal fractions of d-CAPs, and reduced switching probabilities among final d
      CAPs were found in most networks in the PD group, as compared to the NC group.
      Furthermore, an overall negative association between switching probability among
      d-CAPs and disease severity was observed in most networks in the PD group as
      well. These results expand upon previous findings from in vivo
      electrophysiological recording studies in PD. Importantly, this novel analysis
      also demonstrates that changes in network dynamics can be measured using resting
      state fMRI data from subjects with early stage PD.

PMID- 29355773
TI  - Occurrence and distribution of Polycyclic aromatic hydrocarbons (PAHs) in
      seawater, sediments and corals from Hainan Island, China.
AB  - The levels of 16 US EPA priority polycyclic aromatic hydrocarbons (PAHs) were
      investigated in corals, ambient seawater and sediments of Hainan Island, China,
      using gas chromatography - mass spectrometry (GC-MS). The total PAHs (?PAHs)
      concentrations ranged from 273.79 to 407.82ng/L in seawater. Besides, the
      concentrations of ?PAHs in corals 333.88-727.03ng/g dw) were markedly (P < 0.05)
      higher than ambient sediments 67.29-196.99ng/g dw), demonstrating the
      bioaccumulation ability of PAHs by corals. The highest concentration of ?PAHs was
      detected at site S2 in Pavona decussate, which also bore the highest ?PAHs levels
      in both seawater and sediments. The massive corals were more enriched with PAHs
      than the branching corals. Although 2 and 3-ring PAHs were predominant and
      accounted for 69.27-80.46% of the ?PAHs in corals and ambient environment, the
      levels of high molecular weight (HMW) PAHs (4-6 ring) in corals also demonstrated
      their potential dangers for corals and organisms around coral reefs. Biota
      sediment accumulation factor (BSAF) refers to an index of the pollutant absorbed
      by aquatic organisms from the surrounding sediments. The poor correlation between
      log BSAF and log Kow (hydrophobicity) indicated that PAHs in corals maybe not
      bioaccumulate from the ambient sediments but through pathways like absorbing from
      seawater, symbiosis, and feeding. Based on our data, long-term ecological
      monitoring in typical coral reef ecosystems combined with ecotoxicological tests
      of PAHs on corals is necessary to determine the impacts of PAHs on coral reefs.

PMID- 29355774
TI  - A heterogeneous Ly-6B2+ leukocyte population consists of yet undescribed iNOS
      expressing cell types in murine skin wounds.
AB  - The gaseous mediator nitric oxide (NO) is a central regulatory molecule during
      the inflammatory phase of cutaneous tissue repair. The inducible NO-synthase
      (iNOS) represents the main isoform of the three NO producing enzymes at the wound
      site. In particular, keratinocytes and macrophages are described as main sources
      of iNOS-derived NO in skin wounds. Here we provide experimental evidence that Ly
      6B2+ leukocytes are an additional cellular source of iNOS-derived NO in wounds.
      As wound iNOS protein expression temporally coincides with both macrophage and
      neutrophil infiltration, we used immunohistochemistry (IHC) and fluorescence
      activated cell sorting (FACS) to address iNOS expression in both macrophages and
      neutrophil subsets. IHC analyses excluded F4/80+ macrophages as iNOS producers,
      but indicated Ly-6G/C (Gr-1)+ neutrophils to express iNOS in wound granulation
      tissue. A subsequent FACS-based analysis from cellular wound tissue preparations
      revealed an iNOS-expressing fraction of Ly-6B2-determined leukocytes that
      consisted of Ly-6G+ and Ly-6G- cells, meaning that mainly mature neutrophils (Ly
      6B2+/Ly-6G+) as well as inflammatory monocytes (Ly-6B2+/Ly-6G-) are dominant iNOS
      expressing cell types in the developing granulation tissue of acute wounds.

PMID- 29355775
TI  - Real time electrochemical investigation of the release, distribution and
      modulation of nitric oxide in the intestine of individual zebrafish embryos.
AB  - Nitric oxide (NO) is an important signaling molecule that has been implicated in
      a variety of physiological and pathophysiological processes in living organisms.
      NO plays an important role in embryonic development in vertebrates and has been
      reported to influence early organ development and plasticity. Quantifying NO in
      single embryos and their developing organs is challenging because of the small
      size of the embryos, the low dynamically changing concentration and the short
      life-time of NO. Here, we measured the distribution of NO in the intestine of
      live zebrafish (Danio rerio) embryos in physiological conditions and under the
      influence of therapeutic agents. NO measurements were performed using a
      miniaturized electrochemical sensor fabricated on a single carbon fiber (CF)
      which enables quantitative real time in vivo monitoring, and by fluorescence
      imaging using the 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF
      FM-DA) dye. NO production was detected in the middle segment the intestine at a
      level of 3.78 (+/-0.64) MUM, and at lower levels in the anterior and posterior
      segments, 1.08 (+/-0.22) and 1.00 (+/-0.41) MUM respectively. In the presence of
      resveratrol and rosuvastatin, the intestinal NO concentration decreased by 87%
      and 84%, demonstrating a downregulating effect. These results indicate the
      presence of variable micromolar concentrations of NO along the intestine of
      zebrafish embryos and demonstrate the usefulness of CF microelectrodes to measure
      quantitatively the NO release at the level of a single organ in individual
      zebrafish embryos. This work provides a unique approach to study in real time the
      modulatory role of NO in vivo and contributes to further understanding of the
      molecular basis of embryonic development for developmental biology and drug
      screening applications.

PMID- 29355776
TI  - RhoA inactivation by S-nitrosylation regulates vascular smooth muscle contractive
      signaling.
AB  - S-nitrosothiols derived from nitric oxide are known to regulate cell signaling
      through thiol modification. Since small G protein RhoA contains cysteine residues
      in the GTP-binding domain which is critical for its function, modification these
      thiols may alter RhoA activity and lead to changes in the downstream signaling
      such as myosin light chain phosphorylation. However, it is still unclear that if
      RhoA activity and its downstream signals might be modulated by S-nitrosothiols
      and if the two cysteine residues located in the GTP-binding domain are critical
      for the regulation. In this study we show that S-nitroso-L-cysteine (CSNO)
      blocked RhoA activation as determined by either GDP/GTP exchange, active RhoA
      binding to rhotekin or RhoA translocation. CSNO was shown to lead to RhoA
      nitrosylation and RhoA thiol oxidation status was found to be consistent with
      loss of its activity. Mutation of all 6 single cysteine residues to serine showed
      that purified recombinant C20S mutant and C26/20S mutant were resistant to CSNO,
      but interestingly, in the intact cells only the double C16/20S mutant was
      resistant to CSNO. Moreover, inhibition of RhoA activation led to Rho-kinase
      inhibition and inhibition of Rho pathway signaling by CSNO. In both smooth muscle
      cells and aortic tissue, the outcome was inhibition of agonist-stimulated MYPT1
      phosphorylation and reduced levels of myosin light chain phosphorylation. These
      effects of CSNO on MYPT1 and myosin light chain phosphorylation appear to be cGMP
      independent since they were unaffected by inhibition of guanylyl cyclase. In
      contrast to CSNO, spermine NONOate did not alter RhoA GDP/GTP exchange and the
      effects of this compound on myosin light chain phosphorylation were blocked by
      guanylyl cyclase inhibition. And importantly, in C16/20S overexpressed smooth
      muscle cells, MYPT1 phosphorylation was resistant to the inhibitory effect of
      CSNO. Together, these data suggest that S-nitrosothiols regulate myosin light
      chain phosphorylation by inhibiting RhoA/Rho-kinase signaling through
      modification of RhoA cysteine residues at 16 and 20 in its GTP-binding domain,
      which might be an important therapeutic target for diseases with imbalanced
      vascular resistance.

PMID- 29355777
TI  - Redetection of human papillomavirus type 16 infections of the cervix in mid-adult
      life.
AB  - PURPOSE: To assess whether HPV 16 originally detected in adolescent women can be
      redetected in adulthood. METHODS: A convenience sample of 27 adult women with
      known HPV 16 detection during adolescence was assessed for HPV 16 redetection. A
      comparison of the long control region (LCR) DNA sequences was performed on some
      of the original and redetected HPV 16 isolates. RESULTS: Median age at
      reenrollment was 27.5 years (interquartile range of 26.7-29.6). Reenrollment
      occurred six years on average after the original HPV 16 detection. Eleven of 27
      women had HPV 16 redetected. Some of these HPV 16 infections had apparently
      cleared during adolescence. LCR sequencing was successful in paired isolates from
      6 women; in 5 of 6 cases the redetected HPV 16 isolates were identical to those
      detected during adolescence, CONCLUSIONS: HPV 16 may be episodically detected in
      young women, even over long time periods. HPV 16 redetection with identical LCR
      sequences suggests low-level persistent infection rather than true clearance,
      although newly acquired infection with an identical HPV 16 isolate cannot be
      excluded. However, this study suggests that a new HPV 16-positive test in a
      clinical setting may not indicate a new infection.

PMID- 29355778
TI  - Qualitative Evaluation of Individual and Group Well-Child Care.
AB  - OBJECTIVE: Individual well care (IWC) is the standard delivery model for well
      child care in the United States. Alternative models, such as group well care
      (GWC), may create opportunities to enhance care for babies. The purpose of this
      study was to evaluate parents' perceptions of social/wellness benefits and system
      challenges of IWC and GWC. METHODS: Since 2014, we have provided both IWC and GWC
      at an urban academic practice serving a low-income minority community. We
      conducted a mixed method study involving surveys and 18 focus groups (11 IWC
      groups, n = 32 parents; 7 GWC groups, n = 33 parents). Parents completed surveys
      before convening focus group discussions. Survey results were analyzed using
      independent t tests; focus groups were digitally recorded, transcribed, and
      analyzed to identify themes. RESULTS: Both groups had similar demographics:
      parents were mostly female (91%) and black (>80%); about half had incomes <
      $20,000. Parents' mean age was 27 years; children's mean age was 11 months. There
      were no significant differences in overall scores measuring trust in physicians,
      parent empowerment, or stress. IWC parents' themes highlighted ways to improve
      care delivery, while GWC parents highlighted both satisfaction with care delivery
      and social/wellness benefits. GWC parents strongly endorsed this model and
      reported unique benefits, such as garnering social support and learning from
      other parents. CONCLUSIONS: Parents receiving both models of care identified ways
      to improve primary care delivery. Given some of the benefits reported by GWC
      parents, this model may provide the means to enhance resilience in parents and
      children in low-income communities.

PMID- 29355779
TI  - The field effect transistor DNA biosensor based on ITO nanowires in label-free
      hepatitis B virus detecting compatible with CMOS technology.
AB  - In this paper the field-effect transistor DNA biosensor for detecting hepatitis B
      virus (HBV) based on indium tin oxide nanowires (ITO NWs) in label free approach
      has been fabricated. Because of ITO nanowires intensive conductance and
      functional modified surface, the probe immobilization and target hybridization
      were increased strongly. The high resolution transmission electron microscopy
      (HRTEM) measurement showed that ITO nanowires were crystalline and less than 50nm
      in diameter. The single-stranded hepatitis B virus DNA (SS-DNA) was immobilized
      as probe on the Au-modified nanowires. The DNA targets were measured in a linear
      concentration range from 1fM to 10uM. The detection limit of the DNA biosensor
      was about 1fM. The time of the hybridization process for defined single strand
      was 90min. The switching ratio of the biosensor between "on" and "off" state was
      ~ 1.1 * 105. For sensing the specificity of the biosensor, non-complementary,
      mismatch and complementary DNA oligonucleotide sequences were clearly
      discriminated. The HBV biosensor confirmed the highly satisfied specificity for
      differentiating complementary sequences from non-complementary and the mismatch
      oligonucleotides. The response time of the DNA sensor was 37s with a high
      reproducibility. The stability and repeatability of the DNA biosensor showed that
      the peak current of the biosensor retained 98% and 96% of its initial response
      for measurements after three and five weeks, respectively.

PMID- 29355780
TI  - One-pot synthesis of the CuNCs/ZIF-8 nanocomposites for sensitively detecting
      H2O2 and screening of oxidase activity.
AB  - The fluorescent CuNCs/ZIF-8 nanocomposites were facilely prepared by mixing the
      PEI protected CuNCs with the precursors of ZIF-8, and characterized by UV-vis
      absorption, fluorescence, FT-IR, TEM, XRD and XPS. The quantum yield of the
      CuNCs/ZIF-8 is 15 times that of the PEI-CuNCs. Furthermore, the CuNCs/ZIF-8
      possesses better stability and higher fluorescence response due to protective and
      confinement effects of MOFs. It was found that H2O2 could cause much more
      quenching of fluorescent CuNCs/ZIF-8 than that of PEI-CuNCs, which might result
      from enriching H2O2 by ZIF-8. The CuNCs/ZIF-8 can be designed as a fluorescence
      probe to selectively and sensitively detect H2O2 with a linear range from 0.01 to
      1.5uM and a LOD of 0.01uM, while those with PEI-CuNCs are 0.5-30uM and 0.50uM,
      respectively. Through formation of CuNCs/ZIF-8 hybrid, the sensitivity for the
      detection of H2O2 increases by nearly 50-fold, which makes CuNCs/ZIF-8 a
      desirable probe to detect H2O2 content in human serum samples. Also, we
      successfully demonstrated the potential application of the CuNCs/ZIF-8 for
      screening and evaluating activities of oxidase using glucose oxidase as a model.
      The glucose oxidase activity can be detected in a range of 0.1-10mU/L with a LOD
      of 0.1mU/L.

PMID- 29355781
TI  - Facile electrochemiluminescence sensing platform based on high-quantum-yield gold
      nanocluster probe for ultrasensitive glutathione detection.
AB  - This report outlines a highly sensitive and facile electrochemiluminescence (ECL)
      sensing platform based on a novel high-quantum-yield Au-nanocluster (AuNC) probe
      for glutathione (GSH) detection. Owing to the prominent quenching effect of GSH
      on the ECL of the AuNCs, the proposed ECL nanosensor showed a wide response to
      GSH in the ranges of 1.0 * 10-9-1.0 * 10-5M and 1.0 * 10-5-1.0 * 10-1M and a low
      detection limit of 3.2 * 10-10M. In addition, the proposed system exhibited good
      selectivity for GSH in the presence of other chemical/biological interferences.
      Moreover, since no further functionalization of AuNC-based sensor interface was
      necessary, together with the stability, high sensitivity and selectivity of the
      proposed nanosensor, this convenient approach was able to successfully detect GSH
      in both of human urine samples and blood samples with excellent recoveries, which
      indicated its promising application under physiological conditions. Of
      significant importance is that this study not only helps in gaining a better
      understanding of the applicability of the ECL properties of AuNCs, but also
      provides a new avenue for the design and development of ECL sensors based on the
      novel high-quantum-yield AuNC-based probe and other functional-metal-based NC
      probes.

PMID- 29355783
TI  - A standard-driven approach for electronic submission to pharmaceutical regulatory
      authorities.
AB  - OBJECTIVE: Using standards is not only useful for data interchange during the
      process of a clinical trial, but also useful for analyzing data in a review
      process. Any step, which speeds up approval of new drugs, may benefit patients.
      As a result, adopting standards for regulatory submission becomes mandatory in
      some countries. However, preparing standard-compliant documents, such as
      annotated case report form (aCRF), needs a great deal of knowledge and
      experience. The process is complex and labor-intensive. Therefore, there is a
      need to use information technology to facilitate this process. MATERIALS AND
      METHODS: Instead of standardizing data after the completion of a clinical trial,
      this study proposed a standard-driven approach. This approach was achieved by
      implementing a computer-assisted "standard-driven pipeline (SDP)" in an existing
      clinical data management system. SDP used CDISC standards to drive all processes
      of a clinical trial, such as the design, data acquisition, tabulation, etc.
      RESULTS: A completed phase I/II trial was used to prove the concept and to
      evaluate the effects of this approach. By using the CDISC-compliant question
      library, aCRFs were generated automatically when the eCRFs were completed. For
      comparison purpose, the data collection process was simulated and the collected
      data was transformed by the SDP. This new approach reduced the missing data
      fields from sixty-two to eight and the controlled term mismatch field reduced
      from eight to zero during data tabulation. CONCLUSION: This standard-driven
      approach accelerated CRF annotation and assured data tabulation integrity. The
      benefits of this approach include an improvement in the use of standards during
      the clinical trial and a reduction in missing and unexpected data during
      tabulation. The standard-driven approach is an advanced design idea that can be
      used for future clinical information system development.

PMID- 29355782
TI  - An ultrasensitive competitive immunosensor using silica nanoparticles as an
      enzyme carrier for simultaneous impedimetric detection of tetrabromobisphenol A
      bis(2-hydroxyethyl) ether and tetrabromobisphenol A mono(hydroxyethyl) ether.
AB  - Based on our produced polyclonal antibody capable of recognizing
      tetrabromobisphenol A bis(2-hydroxyethyl) ether (TBBPA-DHEE) and
      tetrabromobisphenol A mono(hydroxyethyl) ether (TBBPA-MHEE) (cross-reactivity,
      100% for TBBPA DHEE; 98.7% for TBBPA MHEE), an important derivative and byproduct
      of tetrabromobisphenol A (TBBPA), respectively, a novel ultrasensitive
      competitive immunosensor was established using an electrochemical impedimetric
      strategy for the simultaneous detection of both chemicals. A significantly
      amplified electrochemical impedance spectroscopy (EIS) for quantitative target
      analysis was obtained through (i) the biocatalytic precipitation of 4-chloro-1
      naphthol (CN) on the electrode surface triggered by horseradish peroxidase (HRP)
      and (ii) increased amounts of the enzyme with HRP-loaded silica nanoparticles
      carrying poly-brushes (SiO2@PAA) as labels, achieving a remarkable improvement in
      catalytic performance. Under the optimized conditions, the immunosensor showed
      satisfactory accuracy (recovery, 84.6-118%) and a good linear range (0.21-
      111.31ng/mL) with a limit of detection (LOD) of 0.08ng/mL (S/N = 3) for TBBPA
      DHEE and TBBPA MHEE. In addition, the proposed approach was used to analyse real
      environmental water samples, and our results indicated that this immunosensor had
      great potential for the determination of the trace pollutants in aquatic
      environments.

PMID- 29355784
TI  - User acceptance of location-tracking technologies in health research:
      Implications for study design and data quality.
AB  - Research regarding place and health has undergone a revolution due to the
      availability of consumer-focused location-tracking devices that reveal fine
      grained details of human mobility. Such research requires that participants
      accept such devices enough to use them in their daily lives. There is a need for
      a theoretically grounded understanding of acceptance of different location
      tracking technology options, and its research implications. Guided by an extended
      Unified Theory of Acceptance and Use of Technology (UTAUT), we conducted a 28-day
      field study comparing 21 chronically ill people's acceptance of two leading,
      consumer-focused location-tracking technologies deployed for research purposes:
      (1) a location-enabled smartphone, and (2) a GPS watch/activity tracker.
      Participants used both, and completed two surveys and qualitative interviews.
      Findings revealed that all participants exerted effort to facilitate data
      capture, such as by incorporating devices into daily routines and developing
      workarounds to keep devices functioning. Nevertheless, the smartphone was
      perceived to be significantly easier and posed fewer usability challenges for
      participants than the watch. Older participants found the watch significantly
      more difficult to use. For both devices, effort expectancy was significantly
      associated with future willingness to participate in research although prosocial
      motivations overcame some concerns. Social influence, performance expectancy and
      use behavior were significantly associated with intentions to use the devices in
      participants' personal lives. Data gathered via the smartphone was significantly
      more complete than data gathered via the watch, primarily due to usability
      challenges. To make longer-term participation in location tracking research a
      reality, and to achieve complete data capture, researchers must minimize the
      effort involved in participation; this requires usable devices. For long-term
      location-tracking studies using similar devices, findings indicate that only
      smartphone-based tracking is up to the challenge.

PMID- 29355785
TI  - Efficacy, safety, and economics of bracing after spine surgery: a systematic
      review of the literature.
AB  - BACKGROUND CONTEXT: Bracing is often used after spinal surgery to immobilize the
      spine, improve fusion, and relieve pain. However, controversy exists regarding
      the efficacy, necessity, and safety of various bracing techniques in the
      postsurgical setting. PURPOSE: In this systematic review, we aimed to compare the
      effectiveness, safety, and cost-effectiveness of postoperative bracing versus no
      postoperative bracing after spinal surgery in patients with several common
      operative spinal pathologies. STUDY DESIGN/SETTING: A systematic review was
      carried out to compare postoperative bracing and no postoperative bracing.
      METHODS: A systematic search was conducted of MEDLINE, Embase, and the Cochrane
      Collaboration Library from 1970 to May 2017, supplemented by manual searching of
      the reference list of relevant studies and previously published reviews. Studies
      were included if they compared disability, quality of life, functional
      impairment, radiographic outcomes, cost-effectiveness, or complications between
      patients treated with postoperative bracing and patients not receiving any
      postoperative bracing. Each article was critically appraised independently by two
      reviewers, and the overall body of evidence was rated using guidelines outlined
      by the Grading of Recommendation Assessment, Development and Evaluation (GRADE)
      Working Group. RESULTS: Of the 858 retrieved citations, 5 studies met the
      inclusion criteria and were included in this review, consisting of 4 randomized
      controlled trials and 1 prospective cohort study. Low to moderate evidence
      suggests that there are no significant differences in most measures of
      disability, pain, quality of life, functional impairment, radiographic outcomes,
      and safety between groups. Isolated studies reported statistically significant
      and inconsistent differences between groups with respect to Neck Disability Index
      at 6 weeks postoperatively or Short Form-36 Physical Component Score at 1.5, 3,
      6, and 12 months postoperatively. CONCLUSIONS: Based on limited evidence,
      postoperative bracing does not result in improved outcomes after spinal surgery.
      Future high-quality randomized trials will be required to confirm these findings.

PMID- 29355787
TI  - The potential and perils of prognosticating persistent post-traumatic problems
      from a postpositivist perspective.
AB  - BACKGROUND CONTEXT: Predicting recovery after traumatic neck pain has become an
      active area of research but is moving in several different directions with
      currently little consensus on the important outcomes to predict or relevant
      variables to predict them. PURPOSE: This editorial explores the current state of
      prognostic (risk)-based tools or algorithms for predicting the likelihood of
      chronic problems after acute axial trauma, with a focus on traumatic neck pain
      (ie, whiplash-associated disorder). STUDY DESIGN/SETTING: This paper has an
      editorial study design. METHOD: This is a narrative commentary. RESULTS:
      Prognostic efforts have value in guiding clinical decision-making and optimizing
      resource allocation to those at highest risk while minimizing iatrogenic
      disability for those at lower risk, but there are also several important caveats
      that should be observed when applying and interpreting the results of such tools.
      These include the biases associated with predicting outcomes based on findings
      from a single administration of a tool, inappropriate assumptions of causality,
      assumptions of linear relationships, and inability to consider the unique
      individual traits and contexts of patients that likely interact with clinical
      variables to influence the actual degree of risk they impart. CONCLUSIONS: The
      paper concludes with a brief overview of trends that are likely to dramatically
      change the field, including creation of large clinical databases and big data
      analytics.

PMID- 29355786
TI  - Upregulation of calcium channel alpha-2-delta-1 subunit in dorsal horn
      contributes to spinal cord injury-induced tactile allodynia.
AB  - BACKGROUND CONTEXT: Spinal cord injury (SCI) commonly results not only in motor
      paralysis but also in the emergence of neuropathic pain (NeuP), both of which can
      impair the quality of life for patients with SCI. In the clinical field, it is
      well known that pregabalin, which binds to the voltage-gated calcium channel
      alpha-2-delta-1 (alpha2delta-1) subunit has therapeutic effects on NeuP after
      SCI. A previous study has demonstrated that SCI increased alpha2delta-1 in the L4
      L6 dorsal spinal cord of SCI rats by Western blot analysis and that the increase
      of alpha2delta-1 was correlated with tactile allodynia of the hind paw. However,
      the detailed feature of an increase in alpha2delta-1 protein in the spinal dorsal
      horn and the mechanism of pregabalin effect on SCI-induced NeuP have not been
      fully examined. PURPOSE: This study aimed to examine the detailed distribution of
      alpha2delta-1 expression in the lumbar spinal cord after thoracic SCI in rats and
      the correlation of the therapeutic effect of pregabalin in SCI rats. STUDY
      DESIGN: Male Sprague-Dawley rats underwent thoracic (T10) spinal cord contusion
      injury using the IH impactor device. Spinal cord injury rats received pregabalin
      (30 mg/kg) once a day for 2 weeks over a 4-week period after SCI. METHODS: The
      mechanical threshold in the rat hind paw was measured over 4 weeks. Alpha-2-delta
      1 expression in the lumbar spinal cord and in the dorsal root ganglion (DRG) was
      analyzed using immunohistochemistry and in situ hybridization histochemistry.
      RESULTS: A significant reduction of the withdrawal threshold of mechanical
      stimuli to the hind paw was observed for 2 weeks and continued at least 4 weeks
      after SCI. In the control rats, expression of alpha2delta-1 immunoreactivity was
      detected mainly in laminae I and II in the lumbar dorsal horn. Thoracic SCI
      significantly increased alpha2delta-1 immunoreactivity in laminae I and II in the
      lumbar dorsal horn 4 weeks after SCI; however, thoracic SCI did not affect the
      expression of alpha2delta-1 mRNA in the L4 and L5 DRGs. Meanwhile, the signal
      intensity of alpha2delta-1 mRNAs in the lumbar spinal cord increased from Day 7
      and continued for at least 28 days after SCI. Cellular analysis showed that SCI
      increased the number of alpha2delta-1-expressing cells in laminae I and II. The
      tactile allodynia of the hind paw in the SCI rats was reversed after pregabalin
      treatment and was maintained for 21 days. This administration of pregabalin
      decreased the alpha2delta-1 immunoreactivity significantly in the lumbar dorsal
      horn of thoracic SCI rats at 28 days after SCI. CONCLUSIONS: The present study
      results suggest that an increase of alpha2delta-1 in the L4 and L5 dorsal horns
      after thoracic SCI is derived from the increase in the expression in lumbar
      spinal neurons. This increase may be involved in the development of NeuP in the
      hind paws and the therapeutic effect of pregabalin on central NeuP after SCI.

PMID- 29355788
TI  - The kinetics of autophagy in the lung following acute spinal cord injury in rats.
AB  - BACKGROUND CONTEXT: Lung injury is a major cause of respiratory complications
      following an acute spinal cord injury (ASCI), which are associated with a high
      mortality rate. Autophagy has been shown to be involved in a variety of lung
      diseases; however, whether autophagy is activated in the lung following ASCI
      remains unknown. PURPOSE: The objective of this study was to investigate the
      induction of autophagy in the lung after ASCI. STUDY DESIGN: This is an
      experimental animal study of ASCI investigating kinetics of autophagy in the lung
      following ASCI. METHODS: One hundred and forty-four rats (N=144) were divided
      into two groups: (1) a sham (n=72) and (2) an injury group (n=72). Allen's method
      was used to induce an injury at the level of the 10th thoracic vertebra. Rats
      were sacrificed at 6, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after
      surgery. Lung pathology and apoptosis were assessed to determine the level of
      damage in the lung. LC3, RAB7, P62, and Beclin 1 were used to detect the
      induction of autophagy. The study was funded by the Natural Science Foundation of
      China (NSFC,81272172); National Key Specialty Construction of Clinical Projects
      of China (#2013-544). The funder of the present study had no capacity to
      influence the scholarly conduct of the research, interpretation of results, or
      dissemination of study outcomes. RESULTS: In the injury group, pathologic changes
      (i.e., pulmonary congestion, hemorrhage, inflammatory exudation, and alveolar
      collapse) occurred within the lung tissue within 72 hours after ASCI. Apoptosis
      of the lung cells gradually increased and peaked 72 hours after ASCI. Within 24
      hours of ASCI, LC3 expression decreased, recovered, and gradually increased from
      24 hours to 72 hours. As RAB7 decreased, P62 increased, and the ratio of RAB7/LC3
      significantly decreased. CONCLUSIONS: After ASCI, autophagy in the injured lung
      underwent dynamic changes, as early autophagosome formation decreased and late
      autophagosomes accumulated; thus, autophagy is in a state of inhibition.

PMID- 29355789
TI  - Surgical site infection in spinal metastasis: incidence and risk factors.
AB  - BACKGROUND: Surgical site infection (SSI) in spinal metastasis surgery represents
      the most common postoperative surgical complication with high morbidity and
      mortality. OBJECTIVE: This study aims to evaluate the incidence of SSI in spinal
      metastasis surgery and its risk factors. STUDY DESIGN: This is a retrospective
      analysis of a prospectively collected data. METHODS: Preoperative, operative, and
      postoperative data were collected together with the modified Tokuhashi score and
      Frankel score at all time checkpoints. Surgical site infection was divided into
      superficial and deep SSI, as well as early (<90 days) and late SSI. Multiple
      logistic regression analysis was performed to identify independent risk factors,
      with p<.05 as significance threshold. RESULTS: A total of 297 patients were
      included, with an incidence of SSI of 5.1% (superficial SSI: 3.4%; deep SSI: 1.7
      %). Cervicothoracic surgery was associated with the highest incidence of SSI,
      whereas cervical surgery had the lowest incidence. Smoking, higher number of
      spinal metastasis, elevated body mass index (BMI), and higher ASA (American
      Society of Anesthesiologist) score were the preoperative factors associated with
      increased risk of SSI. Increased intraoperative blood loss and increased number
      of fixed vertebra increased the SSI incidence. SSI increased hospital stay by a
      mean of 12 days. When all these variables are analyzed in a multiple regression
      model, only surgical time>=4 hours and ASA>=3 were found to be independent risk
      factors for the occurrence of SSI. CONCLUSION: This paper represents the largest
      series of spinal metastasis with a mean incidence of SSI of 5.1%. Smoking, higher
      BMI, higher number of spinal metastasis, higher ASA score, higher number of fused
      vertebra, intraoperative bleeding>=2000 mL, and neurologic deterioration are risk
      factors for SSI occurrence. Only ASA>=3 and operative duration>=4 hours are
      independent risk factors for this complication occurrence. Finally, SSI
      occurrence is associated with increased hospital stay, increased 30-day mortality
      rate, and decreased survival rates.

PMID- 29355790
TI  - Small C7-T1 lordotic angle and muscle degeneration at C7 level were independent
      radiological characteristics of patients with cervical imbalance: a propensity
      score-matched analysis.
AB  - BACKGROUND CONTEXT: Cervical sagittal vertical axis (cSVA) of >=40 mm is
      recognized as the key factor of poor health-related quality of life, poor
      surgical outcomes, and correction loss after surgery for cervical deformity.
      However, little is known about the radiological characteristics of patients with
      cSVA>=40 mm. PURPOSE: The purpose of this study was to identify the radiological
      characteristics of patients with cervical imbalance. DESIGN: Retrospective
      analysis of weight-bearing cervical magnetic resonance (MR) images. PATIENT
      SAMPLE: Consecutive 1,500 MR images of symptomatic patients in weight-bearing
      position. OUTCOME MEASURES: Cervical sagittal vertical axis, cervical alignment,
      cervical balance parameters (T1 slope, Co-C2 angle, C2-C7 angle, C7-T1 angle,
      neck tilt, and thoracic inlet angle), disc degeneration (Pfirmann and Suzuki
      classification), end plate degeneration (Modic change), spondylolisthesis (antero
      and retrolisthesis), anteroposterior (AP) diameter of dural sac, cross-sectional
      area (CSA), and fat infiltration ratio of the transversospinalis muscles at C4
      and C7 levels. METHODS: Patients were divided into two groups: cSVA>=40 mm and
      cSVA<40 mm. Gender, age, and cervical alignment were analyzed. Subsequently,
      matched imbalance (cSVA>=40 mm) and control (<40 mm) groups were created using
      the propensity score to adjust for age, gender, and cervical alignment.
      Cervicothoracic angular parameters, disc degeneration, Modic change,
      spondylolisthesis, and degeneration of the transversospinalis muscles at C4 and
      C7 were compared. Variables with p<.05 were included in the multinomial logistic
      regression model to identify factors that relate to the cervical balance
      grouping. RESULTS: The incidence of patients with cervical imbalance was 2.5% (37
      patients). Those patients had a higher incidence of kyphosis, were older, and
      there were more male patients. In the matched imbalance group, the T1 slope was
      greater (p=.028), C7-T1 lordotic angle was smaller (p<.001), the number of
      anterolisthesis was greater (p=.012), and the fat infiltration ratio at C4 and C7
      was higher (p=.023, 0.030) compared with the control. Logistic regression
      analysis showed that the C7-T1 angle (adjusted odds ratio [aOR]=0.592, p=.001)
      and fat infiltration ratio at C7 level (aOR=1.178, p=.030) were significant
      independent variables. CONCLUSIONS: Smaller C7-T1 lordotic angle and severe
      muscle degeneration at C7 level were independent characteristics of patients with
      cervical imbalance.

PMID- 29355791
TI  - Relationships between vitamin D and paraspinal muscle: human data and
      experimental rat model analysis.
AB  - BACKGROUND CONTEXT: Vitamin D deficiency (VDD) has been closely linked with
      skeletal muscle atrophy in many studies, but to date no study has focused on the
      paraspinal muscle. PURPOSE: To verify paraspinal muscle changes according to
      serum vitamin D level. STUDY DESIGN: A cross-sectional study of patients who
      visited our hospital and an in vivo animal study. METHODS: We measured serum
      vitamin D concentration in 91 elderly women and stratified them according to
      their vitamin D status in three groups, control, vitamin D insufficiency, and
      VDD, and obtained magnetic resonance imaging data of the lumbar spine and
      evaluated the quality and quantity of the paraspinal muscles. Additionally, we
      designed experimental rat models for VDD and VDD replacement. Then, we analyzed
      the microcomputed tomography data and histologic data of paraspinal muscles, and
      the histologic data and reverse transcription-quantitative polymerase chain
      reaction data of intramyonuclear vitamin D receptor (VDR) in paraspinal muscle
      through comparison with control rats (n=25, each group). This work was supported
      by a Biomedical Research Institute grant ($40,000), Kyungpook National University
      Hospital (2014). RESULTS: In the human studies, a significant decrease was noted
      in the overall paraspinal muscularity (p<.05) and increase in fatty infiltration
      in the VDD group as compared with the other groups (p<.05). In the rat
      experiment, a decrease was noted in paraspinal muscle fiber size and VDR
      concentration and VDR gene expression level, and total muscle volume of the VDD
      rats as compared with the control rats (p<.05). Vitamin D replacement after VDD
      could partially restore the muscle volume, muscle fiber size, and intramyonuclear
      VDR concentration levels (p<.05) of the paraspinal muscles. CONCLUSIONS: VDD
      induces paraspinal muscle atrophy and decreases the intramyonuclear VDR
      concentration and VDR gene expression level in these muscles. Vitamin D
      replacement contributes to the recovery from atrophy and restoration of
      intramyonuclear VDR concentration in VDD status.

PMID- 29355792
TI  - Does the application site of spinal manipulative therapy alter spinal tissues
      loading?
AB  - BACKGROUND CONTEXT: Previous studies found that the intervertebral disc (IVD)
      experiences the greatest loads during spinal manipulation therapy (SMT). PURPOSE:
      Based on that, this study aimed to determine if loads experienced by spinal
      tissues are significantly altered when the application site of SMT is changed.
      STUDY DESIGN: A biomechanical robotic serial dissection study. SAMPLE: Thirteen
      porcine cadaveric motion segments. OUTCOME MEASURES: Forces experienced by lumbar
      spinal tissues. METHODS: A servo-controlled linear actuator provided standardized
      300 N SMT simulations to six different cutaneous locations of the porcine lumbar
      spine: L2-L3 and L3-L4 facet joints (FJ), L3 and L4 transverse processes (TVP),
      and the space between the FJs and the TVPs (BTW). Vertebral kinematics were
      tracked optically using indwelling bone pins; the motion segment was removed and
      mounted in a parallel robot equipped with a six-axis load cell. Movements of each
      SMT application at each site were replayed by the robot with the intact specimen
      and following the sequential removal of spinal ligaments, FJs and IVD. Forces
      induced by SMT were recorded, and specific axes were analyzed using linear mixed
      models. RESULTS: Analyses yielded a significant difference (p<.05) in spinal
      structures loads as a function of the application site. Spinal manipulative
      therapy application at the L3 vertebra caused vertebral movements and forces
      between L3 and L4 spinal segment in the opposite direction to when SMT was
      applied at L4 vertebra. Additionally, SMT applications over the soft tissue
      between adjacent vertebrae significantly decreased spinal structure loads.
      CONCLUSION: Applying SMT with a constant force at different spinal levels creates
      different relative kinetics of the spinal segments and load spinal tissues in
      significantly different magnitudes.

PMID- 29355793
TI  - Position of the French Working Group on Perioperative Haemostasis (GIHP) on
      viscoelastic tests: What role for which indication in bleeding situations?
AB  - PURPOSE: Viscoelastic tests (VETs), thromboelastography (TEG(r)) and
      thromboelastometry (ROTEM(r)) are global tests of coagulation performed on whole
      blood. They evaluate the mechanical strength of a clot as it builds and develops
      after coagulation itself. The time required to obtain haemostasis results remains
      a major problem for clinicians dealing with bleeding, although some teams have
      developed a rapid laboratory response strategy. Indeed, the value of rapid point
      of-care diagnostic devices such as VETs has increased over the years. However,
      VETs are not standardised and there are few recommendations from the learned
      societies regarding their use. In 2014, the recommendations of the International
      Society of Thrombosis and Haemostasis (ISTH) only concerned haemophilia. The
      French Working Group on Perioperative haemostasis (GIHP) therefore proposes to
      summarise knowledge on the clinical use of these techniques in the setting of
      emergency and perioperative medicine. METHODS: A review of the literature.
      PRINCIPAL FINDINGS: The role of the VETs seems established in the management of
      severe trauma and in cardiac surgery, both adult and paediatric. In other
      situations, their role remains to be defined: hepatic transplantation, postpartum
      haemorrhage, and non-cardiac surgery. They must be part of the global management
      of haemostasis based on algorithms defined in each centre and for each population
      of patients. Their position at the bedside or in the laboratory is a matter of
      discussion between clinicians and biologists. CONCLUSION: VETs must be included
      in algorithms. In consultation with the biology laboratory, these devices should
      be situated according to the way each centre functions.

PMID- 29355794
TI  - Surgical Results of Common Peroneal Nerve Neuroplasty at Lateral Fibular Neck.
AB  - BACKGROUND: Common peroneal nerve (CPN) compressive neuropathy is the most common
      lower-extremity entrapment neuropathy. MATERIALS AND METHODS: A retrospective
      review of a prospectively maintained single-institution database of all patients
      with CPN palsy who underwent decompression and neuroplasty over a 5-year period
      was performed. RESULTS: Thirty patients underwent a neuroplasty of the CPN over a
      5-year period (2010-2015) at our institution. The median age was 45 years, and
      there was a male preponderance. The average time between first onset of symptoms
      to surgery was 122.9 weeks and between first clinic visit and surgery was 21
      weeks. The etiology of the CPN neuropathy was as follows: in 12 patients, it
      followed a surgical procedure and in 14 patients, it occurred after a trauma to
      the lower extremity. In 2 patients, it occurred as a result of a mass lesion
      compromising the nerve and in 1 patient, a local infection predisposed to CPN
      palsy. Right and left lower extremities were equally involved. The median body
      mass index was 28.6. The most common presentation was weakness of the tibialis
      anterior (TA) and extensor hallucis longus (EHL) and loss of sensation in the
      distribution of the CPN or one of its major branches. Pain was a presenting
      symptom in 16 patients. Only 12 of the 30 patients had a positive Tinel's sign at
      the site of compression over the lateral fibular neck. Preoperative
      electrophysiologic confirmation of CPN neuropathy was available in all patients.
      Mean follow-up was 52 weeks. Prone positioning and selective use of the operating
      microscope provided excellent visualization and surgical exposure of the CPN from
      the lower popliteal region to the peroneal tunnel. Average operating room time
      was 170 minutes and average skin-to-skin time 91 minutes. Clinical improvement
      after surgery in terms of motor function was noted in 24 of the 26 patients who
      presented with a motor deficit. The most consistent improvement was noted in the
      TA and EHL; a trend toward greater improvement with shorter time to surgery was
      noted. No complications related to the surgical site or CPN were encountered, and
      no patient had a decline in their neurologic examination as a consequence of the
      surgery. One patient developed a positioning-related right upper-extremity
      brachial plexus neuropraxic injury after surgery that recovered completely.
      CONCLUSIONS: Common peroneal neuropathy usually presents with weakness of the TA
      and EHL and decreased sensation or pain in the distribution of the CPN.
      Microscope-assisted surgical neuroplasty of the CPN at the lateral fibular neck
      with the patient in a prone position allows decompression of the nerve from the
      lower popliteal region to the peroneal tunnel. Significant improvement in motor
      strength after surgery, particularly of the TA and EHL, was observed in this
      series.

PMID- 29355796
TI  - Clinical Utility of Serum Procalcitonin Level and Infection in the Neurosurgical
      Intensive Care Unit.
AB  - BACKGROUND: Procalcitonin, a bloodstream inflammatory biomarker, has proven
      useful in the diagnosis of sepsis in critically ill patients treated in medical
      and surgical intensive care units. This study aims to further our understanding
      of the significance of procalcitonin levels in neuroscience intensive care unit
      (NICU) patients. METHODS: Neurosurgical patients who underwent a procalcitonin
      assay in an NICU over a 2-year period were included in our analysis. A
      procalcitonin level >=0.2 ng/mL was considered a positive result. Infection was
      defined by clinical and/or microbiological diagnosis. Sensitivity, specificity,
      positive predictive value, and negative predictive value in the diagnosis of
      clinically and/or microbiologically identified infection were calculated for
      procalcitonin level >=0.2 ng/mL. RESULTS: The study cohort comprised 203
      patients, including 63 with a positive procalcitonin assay (31%). Meeting the
      criteria for SIRS was the most common reason for a procalcitonin draw (35.5%). A
      procalcitonin level >0.2 ng/mL was not significantly associated with infection (P
      = 0.25). With a 37.4% false-negative rate and a 10.8% false-positive rate, the
      sensitivity of a procalcitonin level >0.2 ng/mL was 35.0%, specificity was 74.4%,
      the positive predictive value was 65.1%, and the negative predictive value was
      45.7%. A receiver operating characteristic analysis revealed an area under the
      curve of 0.61. CONCLUSIONS: Although the utility of procalcitonin in sepsis and
      bacterial pneumonia has been amply demonstrated, this biomarker shows limited
      utility in diagnosing infection in our cohort, emphasizing the importance of
      cautious and selective use of procalcitonin assays in NICU patients.

PMID- 29355795
TI  - Surgical Management of Myelomeningocele-Related Spinal Deformities.
AB  - OBJECTIVE: To evaluate the optimal timing and type of surgical treatment of
      myelomeningocele (MMC)-related spinal deformities and long-term follow-up of
      surgical treatment. METHODS: We reviewed and presented clinical pictures,
      treatment strategies and results of 20 patients with MMC-related spinal
      deformities treated at our center between 2010 and 2017. RESULTS: The average
      patient age was 6.3 years. The average preoperative neurologic status according
      to a modified Japan Orthopedic Association (mJOA) scale was 7.3 points (Benzel's
      modification). Average functional status was 41 points according to a functional
      independent measure scale (FIM). The average angle of kyphosis was 83.7 degrees ,
      that of scoliosis was 36.7 degrees , and that of lordosis was 67 degrees  (Cobb
      angles). The average duration of surgery was 234 minutes, and the average total
      blood loss was 175 mL. The average angle of kyphosis correction was 61 degrees ,
      that of scoliosis correction was 25 degrees , and that of lordosis correction was
      25 degrees  (Cobb angles). The average duration of hospitalization was 16.6 days,
      and the average follow-up was 34.5 months. The total number of complications was
      13. Reoperation was required in 9 cases. Neurologic status according to the mJOA
      scale improved by 0.6 point on average. Functional status according to the FIM
      increased by 6.6 points on average. CONCLUSIONS: Early surgical correction of MMC
      related spinal deformities improves body balance and quality of life. The dual
      growing rod technique is safe and effective in cases of moderate neuromuscular
      spinal deformities at an early age. Kyphectomy is a challenging procedure with
      high complication rates, especially skin problems, but there are no alternative
      procedures for cases of heavy rigid kyphosis.

PMID- 29355797
TI  - CyberKnife Radiosurgery in the Multimodal Management of Patients with Cushing
      Disease.
AB  - BACKGROUND: Surgery is the primary treatment for Cushing disease. When surgery is
      unsuccessful in normalizing hypercortisolism, adjuvant radiation, such as
      stereotactic radiosurgery, may be useful to improve biochemical control. METHODS:
      This retrospective study included a cohort of consecutive patients treated with
      CyberKnife (CK) radiosurgery for active Cushing disease at Stanford Hospital and
      Clinics. RESULTS: As first-line treatment, all patients underwent transsphenoidal
      surgery with histologic demonstration of an adrenocorticotropic hormone-producing
      pituitary adenoma. CK was performed as adjuvant therapy for persistent or
      recurrent disease. The median time between surgery and CK was 14 +/- 34 months.
      Before CK, median maximal diameter of tumors was 9 mm (range, 7-32 mm), with
      cavernous sinus invasion in all patients (100%) and abutment of the optic chiasm
      in 1 patient (14.2%). With an average follow-up of 55.4 months, normalization of
      hypercortisolism was achieved in 4 patients (57.1%): 2 patients (28.5%) achieved
      normalization of the hypothalamic-pituitary-adrenal axis without glucocorticoid
      replacement, and 2 patients developed hypoadrenalism (28.5%). The median time to
      biochemical remission was 12.5 months. Hypopituitarism occurred in only 1 patient
      (14.2%), and no patients had visual complications. Time between surgery and
      radiotherapy of <14 months was associated with a significantly improved
      biochemical remission rate (P = 0.02). CONCLUSIONS: In a cohort of patients with
      Cushing disease, we demonstrate that CK is an effective treatment with rare
      complications.

PMID- 29355798
TI  - Awake Surgery for Gliomas within the Right Inferior Parietal Lobule: New Insights
      into the Functional Connectivity Gained from Stimulation Mapping and Surgical
      Implications.
AB  - OBJECTIVE: Little is known about the functional role of the white matter
      connections running within and around the right inferior parietal lobule (IPL).
      We used direct electrostimulation during awake surgery to investigate this
      connectivity and to avoid permanent deficit after resection for right IPL
      gliomas. METHODS: We reviewed patients who underwent awake mapping for a glioma
      involving the right IPL. Resection was achieved up to functional
      corticosubcortical boundaries detected by electrostimulation. Results of the
      intraoperative mapping were confronted to preoperative and postoperative magnetic
      resonance imaging to perform anatomofunctional correlations. RESULTS: Fourteen
      consecutive patients were enrolled (9 men; mean age, 44 years). Cortically, the
      resection was limited anteriorly by the retrocentral somatosensory area (11
      patients) or by the precentral motor cortex (3 patients). Subcortically, the
      thalamocortical pathways were identified anteriorly in all patients. Articulatory
      disturbances were elicited anteriorly and laterally (6 patients) corresponding to
      the superior longitudinal fasciculus part III. Deeper and superiorly, stimulating
      the superior longitudinal fasciculus part II or the arcuate fasciculus induced
      spatial disorders (6 patients). More laterally and posteriorly, disrupting the
      inferior fronto-occipital fasciculus induced nonverbal semantic disorders (7
      patients). Six patients had visual deficits while the optic radiations were
      stimulated. A total or subtotal resection was achieved in all patients but one.
      There were no permanent impairments, except an expected left superior
      quadrantanopia in 4 patients. CONCLUSIONS: This is the first surgical series
      focusing on right IPL gliomas. The complex functional connectivity detected
      within and around this region fully supports the use of intraoperative multimodal
      functional mapping for optimizing outcomes.

PMID- 29355799
TI  - Seizures After Intracerebral Hemorrhage: Incidence, Risk Factors, and Impact on
      Mortality and Morbidity.
AB  - OBJECTIVE: Spontaneous intracerebral hemorrhage (ICH) is one of the most frequent
      causes of epilepsy in the United States. However, reported risk factors for
      seizure after are inconsistent, and their impact on inpatient morbidity and
      mortality is unclear. We aimed to study the incidence, risk factors, and impact
      of seizures after ICH in a nationwide patient sample. METHODS: We queried the
      Nationwide Inpatient Sample for patients admitted to the hospital with a primary
      diagnosis of ICH between the years 1999 and 2011. Patients were subsequently
      dichotomized into groups of those with a diagnosis consistent with seizure and
      those without. Multivariate logistic regression was used to assess risk factors
      for seizure in this patient sample, and the association between seizures and
      mortality and morbidity. Logistic regression was then used for trend analysis of
      incidence of seizure diagnoses over time. RESULTS: We identified 220,075 patients
      admitted with a primary diagnosis of ICH. Of these, 11.87% had a diagnosis
      consistent with seizure. Factors associated with increased risk of seizure after
      ICH included higher categorical van Walraven score, encephalopathy, alcohol
      abuse, solid tumor, and prior stroke. Seizure was independently associated with
      decreased odds of morbidity (odds ratio [OR], 0.89; 95% confidence interval [CI],
      0.86-0.92) and mortality (OR, 0.75; 95% CI, 0.72-0.77) in multivariate models
      controlling for existing comorbidities. CONCLUSIONS: Seizures after were
      associated with decreased mortality and morbidity despite attempts to correct for
      existing comorbidities. Continuous monitoring of these patients for seizures may
      not be necessary in all circumstances, despite their frequency.

PMID- 29355800
TI  - Surgical Approaches for the Treatment of Multilevel Cervical Ossification of the
      Posterior Longitudinal Ligament: Results of a Decision Analysis.
AB  - BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) often
      leads to cervical myelopathy. Although multiple procedures have been shown to be
      effective in the treatment of OPLL, outcomes are less predictable than in
      degenerative cervical myelopathy, and surgery is associated with high rates of
      complications and reoperation, which affect quality of life. In this study, we
      performed a decision analysis using postoperative complication data and health
      related quality of life (HRQoL) utility scores to assess the average expected
      health utility and 5-year quality-adjusted life years (QALYs) associated with the
      most common surgical approaches for multilevel cervical OPLL. METHODS: We
      searched Medline, EMBASE, and the Cochrane Library for relevant articles
      published between 1990 and October 2017. Meta-analytically pooled complication
      data and HRQoL utility scores associated with each complication were evaluated in
      a long-term model. RESULTS: The overall incidence of perioperative complications
      ranged from 6.2% for laminectomy alone to 11.0% for anterior decompression and
      fusion. Revision surgery for hardware/fusion failure or progression was highest
      for laminectomy alone (3.0%) and lowest for laminectomy and fusion (1.6%).
      Laminoplasty resulted in the highest 5-year QALYs gained, compared with
      laminectomy and anterior approaches (P < 0.001). There was no significant
      difference in QALY gained between laminectomy-fusion and laminoplasty.
      CONCLUSION: The results suggest that owing to the higher rates of complications
      associated with anterior cervical approaches, laminoplasty may result in improved
      long-term outcomes from an HRQoL standpoint. These findings may guide surgeons in
      cases where either procedure is a reasonable option.

PMID- 29355802
TI  - Outcomes of Microsurgical Clipping of Recurrent Aneurysms After Endovascular
      Coiling.
AB  - BACKGROUND: The outcomes of microsurgery of previously coiled aneurysms have been
      poorly described, and little is known about the factors predictive of poor
      outcome. Here we aimed to identify predictors of poor outcome following
      microsurgery for previously coiled recurrent aneurysms. METHODS: In this
      retrospective cohort study of a prospectively maintained vascular database, we
      reviewed presentations, recurrent aneurysm measurements, surgery, and outcomes of
      microsurgical clipping of recurrent previously coiled intracranial aneurysms.
      RESULTS: Our series comprised 39 patients (mean age, 49 years; range, 22-70
      years) who underwent microsurgical clipping of 40 previously coiled intracranial
      aneurysms. One patient suffered seizures, 1 patient experienced transient
      neurologic worsening, and 1 patient developed hyponatraemia, none of whom had
      long-term sequelae. Two patients sustained postoperative infarcts, for an overall
      incidence of permanent morbidity of 5.1%. There were no deaths or rebleeds on
      follow-up. In 3 patients, including the 2 patients with infarct and 1 patient
      with a transient deficit, an attempt was made to remove the coil ball. These
      patients had larger aneurysms (1106 mm3 vs. 135 mm3; P = 0.005), with larger coil
      balls (257 mm3 vs. 52 mm3; P = 0.01) and wider necks (7.09 mm vs. 2.69 mm; P =
      0.02) but smaller remnant heights (1.59 mm vs. 1.99 mm; P = 0.04). They were also
      more likely to have prolapsing coil loops (3/3 vs. 3/27; P = 0.016). CONCLUSIONS:
      Our study demonstrates good clinical outcomes from microsurgical clipping of
      recurrent aneurysms. In the vast majority of cases, clips can be applied
      primarily. Coil ball removal is associated with increased morbidity, and thus
      should be considered only as a second-line option, with the likely need
      identified before the initiation of surgery.

PMID- 29355801
TI  - Endovascular Treatment of Middle Cerebral Artery Dissecting Aneurysms: A 7-Year
      Single-Center Study.
AB  - OBJECTIVE: To evaluate safety and efficacy of endovascular treatment of middle
      cerebral artery dissecting aneurysms (MCADAs). METHODS: Between July 2009 and
      April 2016, 14 patients with MCADAs received endovascular treatment. MCADAs were
      identified by their unique radiographic features on cerebral angiography.
      Baseline characteristics, angiographic features, and angiographic and clinical
      outcomes were analyzed retrospectively. RESULTS: All 14 MCADAs (including 6
      ruptured and 8 unruptured) were successfully treated with the endovascular
      approach. Stent-assisted coiling was used in 12 cases, coil alone in 1 case, and
      parent vessel occlusion in 1 case. Angiographic follow-up data were available for
      all patients at 6 months after treatment. Of 14 MCADAs, 10 were completely
      occluded, and 4 were improved (near occlusion). All parent arteries and covered
      perforators remained patent in the non-parent vessel occlusion group. No ischemic
      strokes or other complications were observed at 1-year clinical follow-up.
      CONCLUSIONS: Our data suggest that endovascular treatment of MCADAs appears to be
      safe and effective. The choice of treatment method needs to be individualized.
      Larger studies are required to evaluate these promising results.

PMID- 29355803
TI  - Full Endoscopic Interlaminar Approach for Nerve Root Decompression of Sacral
      Metastatic Tumor.
AB  - BACKGROUND: Endoscopic surgery has been successfully applied in treatment of
      degenerative spinal disease, but few studies have assessed its use in treating
      sacral metastasis. We report a successful full endoscopic interlaminar approach
      for sacral nerve root decompression of a sacral metastatic tumor. CASE
      DESCRIPTION: An 80-year-old man with a history of hepatocellular carcinoma
      presented with buttock pain with radiation to the right lower leg for 1 week.
      There was also decreased muscle power of the right lower extremity. Lumbosacral
      magnetic resonance imaging revealed metastasis of the sacral spine and right
      iliac bone with S1 exiting nerve root compression. S1 nerve root decompression
      via a full endoscopic interlaminar approach under local anesthesia was performed.
      Under fluorescence guidance, a working sleeve with a beveled opening was placed
      in the interlaminar space of L5-S1. We entered the sacral canal and identified
      the S1 exiting nerve root. A laminotomy was performed from the internal edge of
      the right sacral laminae toward the lateral recess. During decompression of the
      nerve root, buttock and leg pain improved gradually. There was almost complete
      resolution of leg pain after surgery, and the patient recovered the ability to
      walk. Visual analog scale score for pain decreased from 8 to 2 after 3 months of
      follow-up. CONCLUSIONS: For patients with sacral metastasis without spinal
      instability or difficulty lying in prone position under local anesthesia, the
      full endoscopic interlaminar approach for nerve root decompression of sacral
      metastasis may be a suitable method.

PMID- 29355804
TI  - WITHDRAWN: Continuous lumbar cistern drainage before surgical clipping for
      aneurysmal subarachnoid hemorrhage.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29355805
TI  - Fusion Rate and Clinical Outcomes in Two-Level Posterior Lumbar Interbody Fusion.
AB  - BACKGROUND: Posterior lumbar interbody fusion (PLIF) has become a general
      surgical method for degenerative lumbar diseases. Although many reports have
      focused on single-level PLIF, few have focused on 2-level PLIF, and no report has
      covered the fusion status of 2-level PLIF. The purpose of this study is to
      investigate clinical outcomes and fusion for 2-level PLIF by using a combination
      of dynamic radiographs and multiplanar-reconstruction computed tomography scans.
      METHODS: This study consisted of 48 consecutive patients who underwent 2-level
      PLIF for degenerative lumbar diseases. We assessed surgery duration, estimated
      blood loss, complications, clinical outcomes as measured by the Japanese
      Orthopaedic Association score, lumbar sagittal alignment as measured on standing
      lateral radiographs, and fusion status as measured by dynamic radiographs and
      multiplanar-reconstruction computed tomography. Patients were examined at a
      follow-up point of 4.8 +/- 2.2 years after surgery. Thirty-eight patients who did
      not undergo lumbosacral fusion comprised the lumbolumbar group, and 10 patients
      who underwent lumbosacral fusion comprised the lumbosacral group. RESULTS: The
      mean Japanese Orthopaedic Association score improved from 12.1 to 22.4 points by
      the final follow-up examination. Sagittal alignment also was improved. All
      patients had fusion in the cranial level. Seven patients had nonunion in the
      caudal level, and the lumbosacral group (40%) had a significantly poorer fusion
      rate than the lumbolumbar group (97%) did. CONCLUSIONS: Surgical outcomes of 2
      level PLIF were satisfactory. The fusion rate at both levels was 85%. All
      nonunion was observed at the caudal level and concentrated at L5-S level in L4-5
      S PLIF.

PMID- 29355806
TI  - Risk Factors Analyses for Seizure Recurrence in Different Periods After
      Refractory Epilepsy Surgery: A Prospective Single-Center Study.
AB  - OBJECTIVE: To evaluate the potential risk factors associated with seizure
      recurrence in different periods after epilepsy surgery. METHODS: A total of 303
      patients with refractory epilepsy after epilepsy surgery were included. The
      Kaplan-Meier method with log-rank test and univariate and multivariate Cox
      proportional hazards model were performed to calculate the comparison of survival
      curves between groups and identify the risk factors associated with seizure
      recurrence in different periods after surgery. RESULTS: The significant
      predictors of seizure recurrence were determined, including duration of epilepsy
      (P = 0.018), seizure types (P = 0.009), magnetic resonance imaging findings (P =
      0.007), intracranial electroencephalographic recordings (P = 0.002), sides of
      epileptogenic zone (P = 0.025), and types of surgery (P = 0.002). Moreover, the
      significant predictors of seizure recurrence within 12 months after surgery were
      also included, such as gender (P = 0.007), duration of epilepsy (P = 0.013),
      intracranial electroencephalographic recordings (P = 0.003), and types of surgery
      (P < 0.001). Our results indicated that the variables of magnetic resonance
      imaging findings (P = 0.015), sides of epileptogenic zone (P = 0.004), and
      seizure relapse within 12 months after surgery (P < 0.001) were significantly
      associated with seizure recurrence in 12-36 months after surgery. Seizure relapse
      within 12 months after surgery (P < 0.001) was also associated with seizure
      recurrence >36 months after surgery. CONCLUSIONS: We reconfirmed the well-known
      risk factors associated with seizure recurrence and also identified the
      controversial variables. In addition, we found that the risk factors associated
      with seizure recurrence were different in different periods after epilepsy
      surgery.

PMID- 29355807
TI  - Microvascular Brainstem Ischemia After Vestibular Schwannoma Surgery: A Clinical
      and Microanatomic Study.
AB  - OBJECTIVE: To identify a potential microvascular etiology in patients who
      underwent vestibular schwannoma surgery (VSS) complicated by postoperative
      microvascular brainstem ischemia. METHODS: Charts were retrospectively reviewed
      of all patients who had an MRI within 14 days of VSS in years 2005-2016. Patient
      characteristics, preoperative and postoperative imaging features, clinical course
      and potential predictors of brainstem ischemia were recorded. Cadaveric
      dissections of 4 cerebellopontine angle (CPA) cisterns with focus on the anterior
      inferior cerebellar artery (AICA) microvascular were also performed to identify
      candidate vessels and potential etiology. RESULTS: Fifty-four of 258 patients had
      an MRI within 14 days of VSS. Retrosigmoid approach was used in 61.1% of
      patients, translabyrinthine approach in 25.9%, and middle fossa approach in
      13.0%. Four patients (7.4%) had acute microvascular ischemia involving the middle
      cerebellar peduncle (MCP) adjacent to the cranial nerve (CN) VII-VIII complex
      demonstrated on postoperative MRI. A statistically significant association was
      found between the translabyrinthine approach and acute brainstem ischemia (odds
      ratio, 10.6; 95% confidence interval, 1.004-112.7). Dissection of CPAs revealed
      10-20 perforating arteries per specimen originating from the lateral pontine and
      the flocculopeduncular segments of the AICA. Most microvessels travelled in
      retrograde fashion along the anteroinferior surface of the CN VII-VIII complex to
      perforate the cisternal surface of the MCP. No patient had residual or delayed
      neurologic deficits related to brainstem ischemia at final follow-up.
      CONCLUSIONS: While effort should be made to preserve perforating vessels,
      microvascular brainstem ischemia is often asymptomatic and did not lead to
      permanent neurologic deficits in our series.

PMID- 29355808
TI  - Endovascular Mechanical Thrombectomy for Acute Ischemic Stroke Under General
      Anesthesia Versus Conscious Sedation: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Endovascular mechanical thrombectomy (EMT) is the standard of care
      for eligible patients presenting with anterior circulation acute ischemic stroke
      (AIS) due to emergent large vessel occlusion (ELVO). The aim of this systematic
      review and meta-analysis is to compare the outcomes between patients undergoing
      general anesthesia (GA) versus conscious sedation (CS) for these procedures.
      METHODS: A literature review was performed to identify studies reporting the EMT
      outcomes of AIS patients who underwent GA or CS for the procedure. Baseline,
      treatment, and outcomes data were analyzed. Good outcome was defined as a
      modified Rankin Scale score of 0-2 at 3 months, and successful reperfusion was
      defined as modified thrombolysis in cerebral infarction grade of 2b-3. RESULTS:
      Nine studies, comprising a total of 1379 patients treated with GA (n = 761) or CS
      (n = 618) for EMT, were included. Based on pooled data, GA achieved good outcome
      in 35% and successful reperfusion in 81%, whereas CS achieved good outcome in 41%
      and successful reperfusion in 75%. Meta-analyses showed no significant
      differences in the rates of good outcome (P = 0.51) or successful reperfusion (P
      = 0.39) between the GA and CS groups. The rates of pneumonia were significantly
      higher in the GA group (21% vs. 11%; P = 0.01). CONCLUSIONS: The use of either GA
      or CS during EMT for patients with anterior circulation acute ELVO does not yield
      significantly different rates of functional independence at 3 months.

PMID- 29355810
TI  - Successful Use of Covered Stent for Carotid Artery Injury with Active Medial
      Projecting Extravasation.
AB  - BACKGROUND: Nontraumatic carotid artery injury with active extravasation, or
      carotid blowout syndrome (CBS), is relatively rare and highly difficult to treat
      because it is difficult to approach the lesions owing to anatomic factors. It
      also involves quick progression and a risk of cerebral embolization caused by
      thrombi and carotid artery occlusion. Recently, covered stents were revealed to
      be effective for CBS. However, they have several disadvantages, such as their
      costs, rebleeding complications, or cerebral embolic risks. A firm selection
      method of CBS types that are appropriate for covered-stent therapy is expected.
      CASE DESCRIPTION: A 38-year-old man with esophageal cancer presented with massive
      hematemesis. Computed tomography revealed active extravasation from the left
      common carotid artery with medial projection. Initially, the open direct approach
      failed, which resulted in further bleeding and transient cardiopulmonary arrest.
      With tentative hemostasis using manual finger compression, emergency angiography
      was performed, and a covered stent, Fluency 8 mm * 60 mm, was placed at the
      rupture point. He was transferred to the rehabilitation hospital 36 days after
      admission with a modified Rankin score of 2 without major complications.
      CONCLUSION: CBS cases having rupture points around the clavicle and having medial
      projection extravasation should be treated by covered stent placement under
      tentative hemostasis using manual finger pressure rather than conventional open
      surgical treatment.

PMID- 29355809
TI  - Correlation Between Tumor Location and Clinical Properties of Glioblastomas in
      Frontal and Temporal Lobes.
AB  - BACKGROUND: Tumor location is a major prognostic factor in glioblastomas and may
      be associated with clinical properties. This study established and analyzed the
      correlation between tumor location and clinical properties of glioblastomas in
      frontal and temporal lobes. METHODS: This retrospective study determined the
      location of glioblastomas in the frontal lobe (FL) or temporal lobe (TL) based on
      preoperative magnetic resonance imaging. Clinical, radiologic, and molecular
      characteristics of FL and TL glioblastomas were compared to define their clinical
      properties, including sex, age, sides, relationship to ventricle, imaging
      subtypes, volume, isocitrate dehydrogenase mutation, promoter methylation of O6
      methylguanine-DNA methyltransferase, progression-free survival, and overall
      survival. RESULTS: The study enrolled 406 patients (182 [44.83%] in FL group and
      224 [55.17%] in TL group) with a mean age of 69.8 years. Compared with FL group,
      TL group had higher incidence of female patients (P = 0.024), tumor location
      distant to the ventricle (P = 0.006), isocitrate dehydrogenase mutations (P =
      0.021), promoter methylation of O6-methylguanine-DNA methyltransferase (P =
      0.012), and prolonged progression-free survival and overall survival (P < 0.05).
      No significant differences were observed between groups with respect to age >=60
      years at study entry (P = 0.668), sides (P = 0.879), imaging subtypes (P =
      0.362), or volume (P = 0.709). CONCLUSIONS: This study demonstrated that
      different tumor locations are associated with diverse clinical properties of
      glioblastomas in FL and TL. This information will aid in increasing understanding
      of glioblastoma biology for application in baseline comparisons in future
      clinical trials.

PMID- 29355811
TI  - Preoperative Hemoglobin Level is Associated with Increased Health Care Use After
      Elective Spinal Fusion (>=3 Levels) in Elderly Male Patients with Spine
      Deformity.
AB  - BACKGROUND: Measures of health care use such as length of hospital stay (LOS) are
      used as proxies for quality of care after spine surgery. Accordingly, hospitals
      and health systems are investing considerable resources into the preoperative
      identification of patients at risk for prolonged LOS. This study aims to
      investigate the impact of preoperative level on outcomes and LOS after spinal
      fusion. METHODS: The medical records of 204 elderly (>=60 years) male patients
      undergoing elective spinal fusion (>=3 levels) at a major academic institution
      from 2005 to 2015 were reviewed. The lower hemoglobin (Hgb) level was designated
      as <13.5 g/dL. We identified 83 (40.7%) patients with preoperative lower Hgb
      levels and 121 (59.3%) with normal levels (low Hgb, n = 83; normal Hgb, n = 121).
      The primary outcomes investigated were complications and LOS. RESULTS:
      Demographics and comorbidities were similar between both groups, with mean Hgb
      levels being 12.3 +/- 0.9 g/dL and 14.9 +/- 1.0 g/dL for the low and normal
      cohorts, respectively. The lower Hgb cohort experienced higher rates of
      postoperative delirium (21.7% vs. 5.8%; P = 0.0007), non-wound infections (6.0%
      vs. 0.0%; P = 0.006), and hematoma formation (3.6% vs. 0.0%; P = 0.035). There
      was a significant difference in LOS between the cohorts, with the low Hgb cohort
      experiencing approximately a 2-fold increase (low Hgb, 8.1 +/- 5.9 days vs.
      normal Hgb, 4.8 +/- 2.5 days; P < 0.0001). Preoperative Hgb and hematocrit levels
      negatively correlated with LOS (Hgb, R = -0.388, P < 0.001 and Hct, R = -0.2883,
      P < 0.001). CONCLUSIONS: Our study shows that elderly male patients with lower
      preoperative Hgb levels have increased LOS and postoperative delirium after
      spinal fusion. Moreover, preoperative Hgb levels negatively correlate with LOS.

PMID- 29355812
TI  - Lack of cations in flow cytometry buffers affect fluorescence signals by reducing
      membrane stability and viability of Escherichia coli strains.
AB  - Buffers are essential for diluting bacterial cultures for flow cytometry analysis
      in order to study bacterial physiology and gene expression parameters based on
      fluorescence signals. Using a variety of constitutively expressed fluorescent
      proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual
      changes in fluorescence levels after dilution into the commonly used flow
      cytometry buffer phosphate-buffered saline (PBS) and two other buffer solutions,
      Tris-HCl and M9 salts. These changes appeared very rapidly after dilution, and
      were linked to increased membrane permeability and loss in cell viability. We
      observed buffer-related effects in several different E. coli strains, K-12, C and
      W, but not E. coli B, which can be partially explained by differences in
      lipopolysaccharide (LPS) and outer membrane composition. Supplementing the
      buffers with divalent cations responsible for outer membrane stability, Mg2+ and
      Ca2+, preserved fluorescence signals, membrane integrity and viability of E.
      coli. Thus, stabilizing the bacterial outer membrane is essential for precise and
      unbiased measurements of fluorescence parameters using flow cytometry.

PMID- 29355813
TI  - Production, detection and application perspectives of quorum sensing autoinducer
      2 in bacteria.
AB  - Autoinducer-2 (AI-2) is a major signal molecule in bacterial quorum sensing (QS)
      besides N-acyl homoserine lactones (AHLs or AI-1). AI-2 mediated QS pathways have
      been proved to regulate gene expression and physiological behaviors of bacteria
      in either intraspecies or interspecies communication. Recent reviews have mainly
      summarized AI-2 structures, AI-2 mediated QS pathways and the role of AI-2 in
      gene regulation, etc. In this article, we present a comprehensive review of AI-2
      production, detection and applications. Firstly, intracellular AI-2 synthetic
      routes were outlined and environmental influences on AI-2 production were
      focused. Furthermore, recent advances in AI-2 detection and quantification were
      elucidated from an overall perspective. An in-depth understanding of mechanisms
      and features of various detection methods may facilitate development of new
      technologies aimed at signal molecule detection. Finally, utilization of AI-2
      mediated QS in health improvement, water treatment and drug production indicate
      promising and extensive application perspectives of QS strategies.

PMID- 29355814
TI  - Development of a high efficient biocatalyst by oriented covalent immobilization
      of a novel recombinant 2'-N-deoxyribosyltransferase from Lactobacillus animalis.
AB  - The 2'-N-deoxyribosyltransferases [NDT; EC 2.4.2.6] are a group of enzymes widely
      used as biocatalysts for nucleoside biosynthesis. In this work, the molecular
      cloning, expression and purification of a novel NDT from Lactobacillus animalis
      (LaNDT) have been reported. On the other hand, biocatalyst stability has been
      significantly enhanced by multipoint covalent immobilization using a hetero
      functional support activated with nickel-chelates and glyoxyl groups. The
      immobilized enzyme could be reused for more than 300 h and stored during almost 3
      months without activity loss. Besides, the obtained derivative (Ni2+-Gx-LaNDT)
      was able to biosynthesize 88 mg floxuridine/g biocatalyst after 1 h of reaction.
      In this work, a green bioprocess by employing an environmentally friendly
      methodology was developed, which allowed the obtaining of a compound with proven
      anti-tumor activity. Therefore, the obtained enzymatic biocatalyst meets the
      requirements of high activity, stability, and short reaction times needed for low
      cost production in a future preparative application.

PMID- 29355815
TI  - Prophylactic effect of rosmarinic acid on tracheal responsiveness, white blood
      cell count and oxidative stress markers in lung lavage of sensitized rats.
AB  - BACKGROUND: Rosmarinic acid (RA) as an active component of several medicinal
      plants, has shown anti-inflammatory and anti-oxidant effects. In this study, the
      effect of RA on tracheal responsiveness (TR), lung inflammatory cells, oxidant
      biomarkers in sensitized rats were evaluated. METHODS: TR to methacholine and
      ovalbumin (OVA) as well as total and differential white blood cell (WBC) count
      and levels of nitrogen dioxide, nitrate, malondialdehyde, thiol, superoxide
      dismutase, and catalase in bronchoalveolar lavage fluid were measured in control
      (group C) rats, sensitized animals to OVA and given drinking water alone (group
      S), S groups receiving drinking water containing three concentrations of RA
      (0.125, 0.250 and 0.500 mg/mL) and dexamethasone (1.25 MUg/mL), (n = 6 in each
      group). RESULTS: Increased TR to methacholine and OVA, total WBC count,
      percentages of eosinophils, monocytes, neutrophils and levels of oxidant
      biomarkers but decreased other measured parameters were observed in group S
      compared to group C. Percentages of lymphocytes and antioxidant biomarkers were
      significantly increased but other measured parameters were significantly
      decreased in S group treated with dexamethasone and in rats treated with the two
      higher concentrations of RA compared to S group. The effect of RA medium
      concentration on percentage of eosinophils and RA high concentration on total WBC
      count and percentages of eosinophils and lymphocytes, were significantly higher
      than those of dexamethasone. CONCLUSION: These results showed the concentration
      dependent effect of RA on tracheal responses, lung inflammatory cells and oxidant
      antioxidant parameters which was comparable to that of dexamethasone at used
      concentrations in sensitized rats.

PMID- 29355816
TI  - Does status epilepticus modify the effect of ifenprodil on cortical epileptic
      afterdischarges in immature rats?
AB  - BACKGROUND: Ifenprodil as a specific antagonist of NMDA receptors containing a
      dominant NR2B subunit exhibits age-dependent anticonvulsant action. Possible
      changes of this action due to status epilepticus (SE) elicited at early stage of
      development were studied using cortical epileptic afterdischarges (ADs) as a
      model. METHODS: Lithium-pilocarpine SE was induced at postnatal day 12 and
      effects of ifenprodil were studied 3, 6, 9, and 13 days after SE in rat pups with
      implanted epidural electrodes. Controls (LiPAR) received saline instead of
      pilocarpine. ADs were elicited by low frequency stimulation of sensorimotor
      cortex. Intensity of stimulation current increased in 18 steps from 0.2 to 15 mA.
      Ifenprodil (20 mg/kg) was administered intraperitoneally (ip) after the
      stimulation with 3.5-mA current. Threshold for four different phenomena as well
      as duration of ADs were evaluated. RESULTS: The threshold for the transition into
      the limbic type of ADs was higher in 15-day-old SE rats than in LiPAR controls.
      Opposite difference was found in 18-day-old animals, older rats did not exhibit
      any difference. Isolated significant changes in total duration of ADs were found
      after high stimulation intensities. These changes appeared in 18-day-old rats
      where ADs were shorter in SE than in control LiPAR rats. CONCLUSIONS: Changes in
      ifenprodil action were found only in the first week after SE but not in the
      second week. Interpretation of the results is complicated by failure of
      significant differences between SE and LiPAR rats probably due to a high dose of
      paraldehyde.

PMID- 29355817
TI  - The 'healthy worker effect': Do healthy people climb the occupational ladder?
AB  - The association between occupational status and health has been taken to reveal
      the presence of occupational health inequalities. However, that interpretation
      assumes no influence of health status in climbing the occupational ladder. This
      paper documents evidence of non-negligible returns to occupation status on health
      (which we refer as 'healthy worker effect'). We use a unique empirical strategy
      that addresses the problem of reverse causality. That is, an instrumental
      variable strategy using the variation in average health in the migrant's country
      of origin, a health measure plausibly not determined by the migrant's
      occupational status. Our findings suggest that health status exerts significant
      effects on occupational status in several dimensions; including having a
      supervising role, worker autonomy, and worker influence. The effect size of
      health is larger than that of an upper secondary education.

PMID- 29355818
TI  - Bidirectional associations of e-cigarette, conventional cigarette and waterpipe
      experimentation among adolescents: A cross-lagged model.
AB  - PURPOSE: With an increasingly diverse tobacco product market, it is imperative to
      understand the trajectories of product experimentation in order to design
      effective prevention programs. This study aims to explore the bidirectional
      associations of conventional cigarette, e-cigarette and waterpipe experimentation
      in a large adolescent sample. METHODS: Longitudinal assessment of conventional
      cigarette, e-cigarette and waterpipe use initiation was conducted in a school
      based cohort of 1369 9th graders (mean age=14.88 SD=0.48 at baseline) during fall
      2014 and reassessed 6-months later using online self-reported questionnaires.
      Autoregressive cross-lagged analysis within structural equation modeling
      framework was performed to simultaneously estimate the initiation of these
      products over a six-month period, controlling for age, gender, and participation
      in an intervention program to reduce conventional cigarette initiation. RESULTS:
      Tobacco product lifetime use was prevalent at baseline in the sample:
      conventional cigarettes (48.4%), e-cigarettes (35.8%), and waterpipe (20.8%). At
      six-month follow-up, trying conventional cigarettes predicted trying e-cigarette
      (adjusted odds ratio (AOR)=3.78, CI95%: 2.66-5.37) and trying waterpipe
      (AOR=2.82, CI95%: 2.00-3.97). Trying e-cigarette predicted trying conventional
      cigarette (AOR=3.57, CI95%: 1.96-6.49) and trying waterpipe (AOR=1.51, CI95%:
      1.07-2.14). Although trying waterpipe predicted trying e-cigarette at follow-up
      (AOR=2.10, CI95%: 1.30-3.40), its use did not predict trying conventional
      cigarette (AOR=0.55, CI95%: 0.24-1.30). CONCLUSIONS: The high rates of poly
      tobacco use and the bidirectionality of tobacco product experimentation demands
      comprehensive tobacco control and prevention programs that address the
      increasingly diverse tobacco product market targeting adolescents.

PMID- 29355819
TI  - Effects of six weeks of electronic cigarette use on smoking rate, CO, cigarette
      dependence, and motivation to quit smoking: A pilot study.
AB  - OBJECTIVES: Switching from combustible tobacco cigarettes to electronic
      cigarettes (e-cigs) may or may not help smokers to reduce cigarette consumption
      and toxicant exposure. This pilot study investigated the effects of asking
      smokers to switch to e-cigs for 6weeks on smoking, exhaled carbon monoxide (CO)
      concentration, dependence, and motivation to quit smoking. METHODS: Non-treatment
      seeking daily smokers (n=18) were given free e-cigs and instructed to use them
      instead of smoking cigarettes for 6weeks. Smokers were assessed at baseline,
      weekly for 6weeks, and at 8 and 10weeks for cigarettes/day, e-cig use, CO,
      cigarette dependence, and Contemplation Ladder. RESULTS: All participants
      completed 6weeks; 17 completed 10weeks. At Week 6, cigarettes/day were reduced by
      two-thirds and CO by 45% from baseline (p's<.001), with reductions maintained at
      Week 10 (p's<.005). Cigarette dependence scores were a third lower at Weeks 6
      (p<.002) and 10 (p<.001) than at baseline. Contemplation Ladder scores were
      higher at Weeks 6 and 10 (p's<.001) than at baseline. All these statistical
      effect sizes were large. At Week 6, number of reasons not to use e-cigs increased
      (p<.011). CONCLUSIONS: Results show preliminary evidence for beneficial effects
      of short-term switching to e-cigs by non-treatment seeking smokers in terms of
      reduced smoke toxicant exposure and cigarette dependence, and increased
      motivation to quit, all maintained at least 4weeks after free e-cigs were no
      longer provided.

PMID- 29355820
TI  - Association of cytomegalovirus and Epstein-Barr virus with cognitive functioning
      and risk of dementia in the general population: 11-year follow-up study.
AB  - BACKGROUND: Earlier studies have documented an association between
      cytomegalovirus and cognitive impairment, but results have been inconsistent. Few
      studies have investigated the association of cytomegalovirus and Epstein-Barr
      virus with cognitive decline longitudinally. Our aim was to examine whether
      cytomegalovirus and Epstein-Barr virus are associated with cognitive decline in
      adults. METHOD: The study sample is from the Finnish Health 2000 Survey
      (BRIF8901, n = 7112), which is representative of the Finnish adult population.
      The sample was followed up after 11 years in the Health 2011 Survey. In addition,
      persons with dementia were identified from healthcare registers. RESULTS: In the
      Finnish population aged 30 and over, the seroprevalence of cytomegalovirus was
      estimated to be 84% and the seroprevalence of Epstein-Barr virus 98%.
      Seropositivity of the viruses and antibody levels were mostly not associated with
      cognitive performance. In the middle-aged adult group, cytomegalovirus
      serointensity was associated with impaired performance in verbal learning.
      However, the association disappeared when corrected for multiple testing. No
      interactions between infection and time or between the two infections were
      significant when corrected for multiple testing. Seropositivity did not predict
      dementia diagnosis. CONCLUSIONS: The results suggest that adult levels of
      antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a
      significant decline in cognitive function or with dementia at population level.

PMID- 29355822
TI  - Mild prenatal hypoxia-ischemia leads to social deficits and central and
      peripheral inflammation in exposed offspring.
AB  - Hypoxic-ischemic encephalopathy (HIE) resulting from intrauterine or perinatal
      hypoxic-ischemia (HI) is a leading cause of long-term neonatal neurodisability.
      While most studies of long-term outcome have focused on moderate and severe HIE
      in term infants, recent work has shown that those with mild HIE may have subtle
      neurological impairments. However, the impact of mild HI on pre-term infants is
      much less clear given that pre-term birth is itself a risk factor for
      neurodisability. Here we show that mild HI insult alters behaviour, inflammation
      and the corticosterone stress response in a rat model of pre-term HIE. Mild HI
      exposure led to social deficits in exposed offspring at postnatal day 30, without
      impairments in the novel object recognition test nor in the open field test. This
      was also accompanied by elevations in circulating adrenocorticotropic hormone and
      corticosterone indicating an exaggerated stress response. There were also
      elevations in il-1beta and il-6 but not tnf-alpha mRNA and protein in the brain
      and blood samples. In summary we find that a mild HI exposure leads to social
      deficits, central and peripheral inflammation, and an abnormal corticosterone
      response which are three core features of autism spectrum disorder. This shows
      that mild HI exposure may be a risk factor for an abnormal neurodevelopmental
      outcome in pre-term offspring.

PMID- 29355821
TI  - Hepatic acute phase response protects the brain from focal inflammation during
      postnatal window of susceptibility.
AB  - Perinatal inflammation is known to contribute to neurodevelopmental diseases.
      Animal models of perinatal inflammation have revealed that the inflammatory
      response within the brain is age dependent, but the regulators of this variation
      remain unclear. In the adult, the peripheral acute phase response (APR) is known
      to be pivotal in the downstream recruitment of leukocytes to the injured brain.
      The relationship between perinatal brain injury and the APR has not been
      established. Here, we generated focal inflammation in the brain using interleukin
      (IL)-1beta at postnatal day (P)7, P14, P21 and P56 and studied both the central
      nervous system (CNS) and hepatic inflammatory responses at 4 h. We found that
      there is a significant window of susceptibility in mice at P14, when compared to
      mice at P7, P21 and P56. This was reflected in increased neutrophil recruitment
      to the CNS, as well as an increase in blood-brain barrier permeability. To
      investigate phenomena underlying this window of susceptibility, we performed a
      dose response of IL-1beta. Whilst induction of endogenous IL-1beta or
      intercellular adhesion molecule (ICAM)-1 in the brain and induction of a hepatic
      APR were dose dependent, the recruitment of neutrophils and associated blood
      brain barrier breakdown was inversely proportional. Furthermore, in contrast to
      adult animals, an additional peripheral challenge (intravenous IL-1beta) reduced
      the degree of CNS inflammation, rather than exacerbating it. Together these
      results suggest a unique window of susceptibility to CNS injury, meaning that
      suppressing systemic inflammation after brain injury may exacerbate the damage
      caused, in an age-dependent manner.

PMID- 29355823
TI  - The influence of immunological stressors on traumatic brain injury.
AB  - Traumatic brain injury (TBI) is a leading cause of death and disability
      worldwide, and typically involves a robust immune response. Although a great deal
      of preclinical research has been conducted to identify an effective treatment,
      all phase III clinical trials have been unsuccessful to date. These translational
      shortcomings are in part due to a failure to recognize and account for the
      heterogeneity of TBI, including how extracranial factors can influence the
      aftermath of TBI. For example, most preclinical studies have utilized isolated
      TBI models in young adult males, while clinical trials typically involve highly
      heterogeneous patient populations (e.g., different mechanisms of injury, a range
      of ages, presence of polytrauma or infection). This paper will review the
      current, albeit limited literature related to how TBI is affected by common
      concomitant immunological stressors. In particular, discussion will focus on
      whether extracranial trauma (i.e., polytrauma), infection, and
      age/immunosenescence can influence TBI pathophysiology, and thereby may result in
      a different brain injury than what would have occurred in an isolated TBI. It is
      concluded that these immunological stressors are all likely to be TBI modifiers
      that should be further studied and could impact translational treatment
      strategies.

PMID- 29355824
TI  - Next-Generation Sequencing for Lymphomas: Perfecting a Pipeline for Personalized
      Pathobiologic and Prognostic Predictions.
AB  - This commentary highlights the article by Hung et al that details the design and
      implementation of a 32-gene next-generation sequencing panel for lymphomas and
      compares hybrid-capture with amplicon-based next-generation sequencing
      approaches.

PMID- 29355825
TI  - Evaluation of a Pan-Leishmania Spliced-Leader RNA Detection Method in Human Blood
      and Experimentally Infected Syrian Golden Hamsters.
AB  - Several methods have been developed for the detection of Leishmania, mostly
      targeting the minicircle kinetoplast DNA (kDNA). A new RNA real-time quantitative
      PCR (qPCR) assay was developed targeting the conserved and highly expressed
      spliced-leader (SL) mini-exon sequence. This study compared the limits of
      detection of various real-time PCR assays in hamsters infected with Leishmania
      infantum, in spiked human blood, and in clinical blood samples from visceral
      leishmaniasis patients. The SL-RNA assay showed an excellent analytical
      sensitivity in tissues (0.005 and 0.002 parasites per mg liver and spleen,
      respectively) and was not prone to false-positive reactions. Evaluation of the SL
      RNA assay on clinical samples demonstrated lower threshold cycle values than the
      kDNA qPCR, an excellent interrun stability of 97%, a 93% agreement with the kDNA
      assay, and an estimated sensitivity, specificity, and accuracy of 93.2%, 94.3%,
      and 93.8%, respectively. The SL-RNA qPCR assay was equally efficient for
      detecting Leishmania major, Leishmania tropica, Leishmania mexicana, Leishmania
      guayensis, Leishmania panamensis, Leishmania braziliensis, L. infantum, and
      Leishmania donovani and revealed similar SL-RNA levels in the different species
      and the occurrence of polycistronic SL-containing transcripts in Viannia species.
      Collectively, this single SL-RNA qPCR assay enables universal Leishmania
      detection and represents a particularly useful addition to the widely used kDNA
      assay in clinical studies in which the detection of viable parasites is pivotal
      to assess parasitological cure.

PMID- 29355826
TI  - Improvement in access to safe water, household water insecurity, and time
      savings: A cross-sectional retrospective study in Kenya.
AB  - This study uses a cross-sectional survey (n = 557) with a retrospective design to
      examine relationships between improvement in access to safe water supply (i.e.
      extension of municipal piped water) and a range of social outcomes including
      water insecurity, household time savings and allocation, and household water
      expenditure in Usoma, Kenya. Data were collected in July 2016, about 3 years
      after the intervention, using a modified version of the Household Water
      Insecurity Access Scale (HWIAS). Having assessed the validity and reliability of
      the modified HWIAS, we examine how differences in levels of access to safe water
      influence reported levels of water insecurity as well as amount of money and time
      savings, post the water intervention. Findings suggest that higher levels of
      access reduce risk of water insecurity. Households with piped water on premises
      scored 2.95 points less on the water insecurity scale compared to households with
      access to unimproved sources. As anticipated, time saved on water collection was
      re-directed to income generating activities, while money saved was spent
      primarily on food. Important gender differences were reported, with female headed
      households having 1.15 points less on the HWIAS than male headed households. This
      study establishes an innovative approach to evaluating water interventions that
      can be used in program design and evaluation. The study also emphasises the need
      for universal access to safe water as envisioned in the Sustainable Development
      Goals (SDGs).

PMID- 29355827
TI  - Pathways linking war and displacement to parenting and child adjustment: A
      qualitative study with Syrian refugees in Lebanon.
AB  - Forcibly displaced children are at risk of a range of negative outcomes, yet
      little is known about how to support war-affected caregivers in promoting
      children's psychosocial resilience. The current study uses qualitative methods to
      examine the mechanisms underlying the effects of war and displacement on
      parenting and child adjustment in order to inform intervention development. In
      April and November 2016, group and individual interviews were conducted with 39
      Syrian parents and 15 children in partnership with a humanitarian organization in
      Lebanon. Interviews were transcribed and analyzed using a grounded theory
      approach. Results show three interrelated pathways linking daily displacement
      stressors to various dimensions of parenting: (1) economic hardship prevents
      parents from meeting their children's basic needs and forces adaptation
      strategies that impair positive parent-child interactions; (2) parental
      psychological distress contributes to harsh parenting; and (3) perceptions and
      experiences of insecurity in the community results in increased parental control.
      Greater economic resources and social support emerged as potential protective
      factors for maintaining positive parenting despite exposure to war and
      displacement-related adversity. Our findings suggest that implementation of
      policies and programs to remove structural barriers to refugees' physical and
      economic security can have tangible impacts on parental mental health, parenting
      quality, and child psychosocial outcomes. Future research priorities include a
      stronger focus on the effects of war and displacement on family processes, taking
      into account interactions with the broader social, economic and political
      context.

PMID- 29355829
TI  - The impact of social expenditure on health inequalities in Europe.
AB  - Welfare states are assumed to play a fundamental role in the protection and
      promotion of the health and socioeconomic well-being of citizens. However,
      empirical evidence on the effect of the welfare state is still contradictory. The
      inconsistency of the results has led researchers to a lack of consensus in
      defining the mechanisms that might explain the relationship between the welfare
      state and health. To shed some light on the current debate, we rely on individual
      and country data from the European Social Survey (ESS) and Eurostat to explore
      the direct and indirect effects of the welfare state on health inequalities in a
      sample of European countries. We use multilevel models to test the hypothesized
      impact of social expenditure on reducing health inequalities. Firstly, results
      show that health inequalities are lower in countries where social expenditure is
      higher. Secondly, the relationship between socio-economic status (SES) and health
      is moderated by social expenditure. The positive effect of SES on health
      decreases in countries where social expenditure is higher, while this effect is
      higher in countries with lower social expenditure. Our findings suggest that
      social spending has a positive impact on equalizing health conditions in Europe.

PMID- 29355830
TI  - Factors associated with non-adherence to HBV antiviral therapy.
AB  - BACKGROUND: HBV antiviral therapy has the potential to reduce the burden of HBV
      related liver disease by suppressing HBV DNA replication to undetectable levels,
      reducing the progression of liver fibrosis and reducing the risk of
      hepatocellular carcinoma (HCC) development. Treatment outcomes and long-term
      benefits require adherence to medication regimens. This study aimed to identify
      the prevalence and factors associated with non-adherence to antiviral therapy.
      METHODS: A cross-sectional survey of patients receiving HBV antiviral therapies
      was conducted in three Sydney hospitals. Participants were asked to complete an
      online questionnaire. Logistic regression was used to assess the associations
      between non-adherence (defined as missing more than 1 day of medication in the
      last 30 days) and demographic, socio-economic, disease, treatment, health-care
      system and individual-related factors. RESULTS: Of the 277 participants, 66
      (23.8%) were non-adherent, missing a mean 1.7 days of medication (sd 4.8) in the
      last 30 days. In multivariate analysis, non-adherent behaviour declined with age
      (odds ratio [OR] 0.9, 95% CI 0.97, 0.99; P<0.013). Participants who reported
      having no established routine to take their medication (OR 5.0, 95% CI 1.4, 17.4;
      P<0.012) and having inadequate health literacy (OR 2.7, 95% CI 1.3, 5.5; P<0.007)
      were more likely to be non-adherent. CONCLUSIONS: Almost a quarter of
      participants in the current study were non-adherent. Adherence is potentially
      modifiable through person-centred education, collaborative models of patient care
      and interventions designed to improve health literacy and establish medication
      routines. Findings have the potential to improve health service delivery to
      patients at risk of non-adherence to HBV antiviral therapy.

PMID- 29355831
TI  - Coherent control of single electrons: a review of current progress.
AB  - In this report we review the present state of the art of the control of
      propagating quantum states at the single-electron level and its potential
      application to quantum information processing. We give an overview of the
      different approaches that have been developed over the last few years in order to
      gain full control over a propagating single-electron in a solid-state system.
      After a brief introduction of the basic concepts, we present experiments on
      flying qubit circuits for ensemble of electrons measured in the low frequency
      (DC) limit. We then present the basic ingredients necessary to realise such
      experiments at the single-electron level. This includes a review of the various
      single-electron sources that have been developed over the last years and which
      are compatible with integrated single-electron circuits. This is followed by a
      review of recent key experiments on electron quantum optics with single
      electrons. Finally we will present recent developments in the new physics that
      has emerged using ultrashort voltage pulses. We conclude our review with an
      outlook and future challenges in the field.

PMID- 29355832
TI  - Morphological control of seedlessly-synthesized gold nanorods using binary
      surfactants.
AB  - High purity gold nanorods (AuNRs) with tunable morphology have been synthesized
      through a binary-surfactant seedless method, which enables the formation of
      monocrystalline AuNRs with diameters between 7 and 35 nm. The protocol has high
      shape yield and monodispersity, demonstrating good reproducibility and
      scalability allowing synthesis of batches 0.5 l in volume. Morphological control
      has been achieved through the adjustment of the molar concentrations of
      cetyltrimethylammonium bromide and sodium oleate in the growth solution,
      providing fine tuning of the optical scattering and absorbance properties of the
      AuNRs across the visible and NIR spectrum. Sodium oleate was found to provide
      greatest control over the aspect ratio (and hence optical properties) with
      concentration changes between 10 and 23 mM leading to variation in the aspect
      ratio between 2.8 and 4.8. Changes in the geometry of the end-caps were also
      observed as a result of manipulating the two surfactant concentrations.

PMID- 29355828
TI  - Neighborhood built environment and cognition in non-demented older adults: The
      Multi-Ethnic Study of Atherosclerosis.
AB  - Preliminary studies suggest that neighborhood social and built environment (BE)
      characteristics may affect cognition in older adults. Older adults are
      particularly vulnerable to the neighborhood environment due to a decreasing range
      of routine travel with increasing age. We examined if multiple neighborhood BE
      characteristics are cross-sectionally associated with cognition in a diverse
      sample of older adults, and if the BE-cognition associations vary by individual
      level demographics. The sample included 4539 participants from the Multi-Ethnic
      Study of Atherosclerosis. Multivariable linear regression was used to examine the
      associations between five BE measures and four cognitive measures, and effect
      modification by individual-level education and race/ethnicity. In the overall
      sample, increasing social destination density, walking destination density, and
      intersection density were associated with worse overall cognition, whereas
      increasing proportion of land dedicated to retail was associated with better
      processing speed. Effect modification results suggest that the association
      between urban density and worse cognition may be limited to or strongest in those
      of non-white race/ethnicity. Although an increase in neighborhood retail
      destinations was associated with better cognition in the overall sample, these
      results suggest that certain BE characteristics in dense urban environments may
      have a disproportionately negative association with cognition in vulnerable
      populations. However, our findings must be replicated in longitudinal studies and
      other regional samples.

PMID- 29355833
TI  - Multi-functional spintronic devices based on boron- or aluminum-doped silicene
      nanoribbons.
AB  - Zigzag silicene nanoribbons (ZSiNRs) in the ferromagnetic edge ordering have a
      metallic behavior, which limits their applications in spintronics. Here a
      robustly half-metallic property is achieved by the boron substitution doping at
      the edge of ZSiNRs. When the impurity atom is replaced by the aluminum atom, the
      doped ZSiNRs possess a spin semiconducting property. Its band gap is suppressed
      with the increase of ribbon's width, and a pure thermal spin current is achieved
      by modulating ribbon's width. Moreover, a negative differential thermoelectric
      resistance in the thermal charge current appears as the temperature gradient
      increases, which originates from the fact that the spin-up and spin-down thermal
      charge currents have diverse increasing rates at different temperature gradient
      regions. Our results put forward a promising route to design multi-functional
      spintronic devices which may be applied in future low-power-consumption
      technologies.

PMID- 29355834
TI  - Creation of nanosized holes in graphene planes for improvement of rate capability
      of lithium-ion batteries.
AB  - Holes with an average size of 2-5 nm have been created in graphene layers by
      heating of graphite oxide (GO) in concentrated sulfuric acid followed by
      annealing in an argon flow. The hot mineral acid acts simultaneously as a
      defunctionalizing and etching agent, removing a part of oxygen-containing groups
      and lattice carbon atoms from the layers. Annealing of the holey reduced GO at
      800  degrees C-1000  degrees C causes a decrease of the content of residual
      oxygen and the interlayer spacing thus producing thin compact stacks from holey
      graphene layers. Electrochemical tests of the obtained materials in half-cells
      showed that the removal of oxygen and creation of basal holes lowers the capacity
      loss in the first cycle and facilitates intercalation-deintercalation of lithium
      ions. This was attributed to minimization of electrolyte decomposition reactions,
      easier desolvation of lithium ions near the hole boundaries and appearance of
      multiple entrances for the naked ions into graphene stacks.

PMID- 29355835
TI  - Alkali-resistant low-temperature atomic-layer-deposited oxides for optical fiber
      sensor overlays.
AB  - This paper presents an investigation of properties of selected metallic oxides
      deposited at a low temperature (100  degrees C) by atomic layer deposition (ALD)
      technique, relating to their applicability as thin overlays for optical fiber
      sensors resistant in alkaline environments. Hafnium oxide (Hf x O y with y/x
      approx. 2.70), tantalum oxide (Ta x O y with y/x approx. 2.75) and zirconium
      oxide (Zr x O y with y/x approx. 2.07), which deposition was based, respectively,
      on tetrakis(ethylmethyl)hafnium, tantalum pentachloride and
      tetrakis(ethylmethyl)zirconium with deionized water, were tested as thin layers
      on planar Si (100) and glass substrates. Growth per cycle (GPC) in the ALD
      processes was 0.133-0.150 nm/cycle. Run-to-run GPC reproducibility of the ALD
      processes was best for Hf x O y (0.145 +/- 0.001 nm/cycle) and the poorest for Ta
      x O y (0.133 +/- 0.003 nm/cycle). Refractive indices n of the layers were 2.00
      2.10 (at the wavelength lambda = 632 nm), with negligible k value (at lambda for
      240-930 nm). The oxides examined by x-ray diffractometry proved to be amorphous,
      with only small addition of crystalline phases for the Zr x O y . The surfaces of
      the oxides had grainy but smooth topographies with root-mean square roughness
      ~0.5 nm (at 10 * 10 MUm2 area) according to atomic force microscopy.
      Ellipsometric measurements, by contrast, suggest rougher surfaces for the Zr x O
      y layers. The surfaces were also slightly rougher on the glass-based samples than
      on the Si-based ones. Nanohardness and Young modules were 4.90-8.64 GPa and 83.7
      104.4 GPa, respectively. The tests of scratch resistance revealed better
      tribological properties for the Hf x O y and the Ta x O y than for the Zr x O y .
      The surfaces were hydrophilic, with wetting angles of 52.5 degrees -62.9 degrees
      . The planar oxides on Si, being resistive even to concentrated alkali (pH 14),
      proved to be significantly more alkali-resistive than Al2O3. The Ta x O y overlay
      was deposited on long-period grating sensor induced in optical fiber. Thanks to
      such an overlay the sensor proved to be long-lasting resistant when exposed to
      alkaline environment with a pH 9. Thereby, it also proved that it has a potential
      to be repeatedly reused as a regenerable optical fiber biosensor.

PMID- 29355836
TI  - Potentialities of silicon nanowire forests for thermoelectric generation.
AB  - Silicon is a material with very good thermoelectric properties, with regard to
      Seebeck coefficient and electrical conductivity. Low thermal conductivities, and
      hence high thermal to electrical conversion efficiencies, can be achieved in
      nanostructures, which are smaller than the phonon mean free path but large enough
      to preserve the electrical conductivity. We demonstrate that it is possible to
      fabricate a leg of a thermoelectric generator based on large collections of long
      nanowires, placed perpendicularly to the two faces of a silicon wafer. The
      process exploits the metal assisted etching technique which is simple, low cost,
      and can be easily applied to large surfaces. Copper can be deposited by
      electrodeposition on both faces, so that contacts can be provided, on top of the
      nanowires. Thermal conductivity of silicon nanowire forests with more than 107
      nanowires mm-2 have been measured; the result is comparable with that achieved by
      several groups on devices based on few nanowires. On the basis of the measured
      parameters, numerical calculations of the efficiency of silicon-based
      thermoelectric generators are reported, and the potentialities of these devices
      for thermal to electrical energy conversion are shown. Criteria to improve the
      conversion efficiency are suggested and described.

PMID- 29355837
TI  - Effect of graphene nanofillers on the enhanced thermoelectric properties of
      Bi2Te3 nanosheets: elucidating the role of interface in de-coupling the
      electrical and thermal characteristics.
AB  - In this report, we investigate the effect of graphene nanofillers on the
      thermoelectric properties of Bi2Te3 nanosheets and demonstrate the role of
      interface for enhancing the overall figure of merit (ZT) ~ 53%. The enhancement
      in the ZT is obtained due to an increase in the electrical conductivity (~111%)
      and decrease in the thermal conductivity (~12%) resulting from increased
      conducting channels and phonon scattering, respectively at the interfaces between
      graphene and Bi2Te3 nanosheets. A detailed analysis of the thermal conductivity
      reveals ~4 times decrease in the lattice thermal conductivity in contrast to ~2
      times increase in the electronic thermal conductivity after the addition of
      graphene. Kelvin probe measurements have also been carried which reveals presence
      of low potential barrier at the interface between graphene and Bi2Te3 nanosheets
      which assist the flow of charge carriers thereby, increasing the mobility of the
      carriers. Thus, our results reveals a significant decrease in the lattice thermal
      conductivity (due to the formation of interfaces) and increase in the electron
      mobility (due to conducting paths at the interfaces) strongly participate in
      deciding observed enhancement in the thermoelectric figure of merit.

PMID- 29355838
TI  - Synthesis of polyaniline (PANI) and functionalized polyaniline (F-PANI)
      nanoparticles with controlled size by solvent displacement method. Application in
      fluorescence detection and bacteria killing by photothermal effect.
AB  - Polyaniline nanoparticles (PANI-NPs) were easily obtained applying the solvent
      displacement method by using N-methylpyrrolidone (NMP) as good solvent and water
      as poor solvent. Different polymers such as polyvinylpyrrolidone (PVP),
      chondroitin sulfate (ChS), polyvinyl alcohol (PVA), and polyacrylic acid (PAA)
      were used as stabilizers. Dynamic light scattering and scanning electron
      microscopy corroborated the size and morphology of the formed NPs. It was
      demonstrated that the size of nanoparticles could be controlled by setting the
      concentration of PANI in NMP, the NMP to water ratio, and the stabilizer's
      nature. The functionalization and fluorescence of NPs were checked by
      spectroscopic techniques. Since polyaniline show only weak intrinsic
      luminescence, fluorescent groups were linked to the polyaniline chains prior to
      the nanoparticle formation using a linker. Polyaniline chains were functionalized
      by nucleophilic addition of cysteamine trough the thiol group thereby
      incorporating pendant primary aliphatic amine groups to the polyaniline backbone.
      Then, dansyl chloride (DNS-Cl), which could act as an extrinsic chromophore, was
      conjugated to the amine pendant groups. Later, the functionalized polyaniline was
      used to produce nanoparticles by solvent displacement. The optical and functional
      properties of fluorescent nanoparticles (F-PANI-NPs) were determined. F-PANI-NPs
      in the conductive state (pH < 4) are able to absorb near infrared radiation (NIR)
      creating a photothermal effect in an aqueous medium. Thus, multifunctional
      nanoparticles are obtained. The application of NIR on a F-PANI-NPs dispersion in
      contact with Pseudomonas aeruginosa causes bacterial death. Therefore, the F-PANI
      NPs could be tracked and applied to inhibit different diseases caused by
      pathogenic microorganisms and resistant to antibiotics as well as a new
      disinfection method to surgical materials.

PMID- 29355839
TI  - Electronic phase separation in insulating (Ga, Mn) As with low compensation:
      super-paramagnetism and hopping conduction.
AB  - In the present work, low compensated insulating (Ga,Mn)As with 0.7% Mn is
      obtained by ion implantation combined with pulsed laser melting. The sample shows
      variable-range hopping transport behavior with a Coulomb gap in the vicinity of
      the Fermi energy, and the activation energy is reduced by an external magnetic
      field. A blocking super-paramagnetism is observed rather than ferromagnetism.
      Below the blocking temperature, the sample exhibits a colossal negative
      magnetoresistance. Our studies confirm that the disorder-induced electronic phase
      separation occurs in (Ga,Mn)As samples with a Mn concentration in the insulator
      metal transition regime, and it can account for the observed superparamagnetism
      and the colossal magnetoresistance.

PMID- 29355840
TI  - Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis
      and lymphatic metastasis.
AB  - The prognosis for bladder cancer patients with lymph node (LN) metastasis is
      dismal and only minimally improved by current treatment modalities. Elucidation
      of the molecular mechanisms that underlie LN metastasis may provide clinical
      therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a
      long noncoding RNA LINC00958, which we have termed bladder cancer-associated
      transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer
      and correlated with LN metastasis. Overexpression of BLACAT2 promoted bladder
      cancer-associated lymphangiogenesis and lymphatic metastasis in both cultured
      bladder cancer cell lines and mouse models. Furthermore, we demonstrate that
      BLACAT2 epigenetically upregulated VEGF-C expression by directly associating with
      WDR5, a core subunit of human H3K4 methyltransferase complexes. Importantly,
      administration of an anti-VEGF-C antibody inhibited LN metastasis in BLACAT2
      overexpressing bladder cancer. Taken together, these findings uncover a molecular
      mechanism in the lymphatic metastasis of bladder cancer and indicate that BLACAT2
      may represent a target for clinical intervention in LN-metastatic bladder cancer.

PMID- 29355842
TI  - Aberrant TGF-beta activation in bone tendon insertion induces enthesopathy-like
      disease.
AB  - Enthesopathy is a disorder of bone, tendon, or ligament insertion. It represents
      one-fourth of all tendon-ligament diseases and is one of the most difficult
      tendon-ligament disorders to treat. Despite its high prevalence, the exact
      pathogenesis of this condition remains unknown. Here, we show that TGF-beta was
      activated in both a semi-Achilles tendon transection (SMTS) mouse model and in a
      dorsiflexion immobilization (DI) mouse model of enthesopathy. High concentrations
      of active TGF-beta recruited mesenchymal stromal stem cells (MSCs) and led to
      excessive vessel formation, bone deterioration, and fibrocartilage calcification.
      Transgenic expression of active TGF-beta1 in bone also induced enthesopathy with
      a phenotype similar to that observed in SMTS and DI mice. Systemic inhibition of
      TGF-beta activity by injection of 1D11, a TGF-beta-neutralizing antibody, but not
      a vehicle antibody, attenuated the excessive vessel formation and restored
      uncoupled bone remodeling in SMTS mice. 1D11-treated SMTS fibrocartilage had
      increased proteoglycan and decreased collagen X and matrix metalloproteinase 13
      expression relative to control antibody treatment. Notably, inducible knockout of
      the TGF-beta type II receptor in mouse MSCs preserved the bone microarchitecture
      and fibrocartilage composition after SMTS relative to the WT littermate controls.
      Thus, elevated levels of active TGF-beta in the enthesis bone marrow induce the
      initial pathological changes of enthesopathy, indicating that TGF-beta inhibition
      could be a potential therapeutic strategy.

PMID- 29355841
TI  - JAK2/IDH-mutant-driven myeloproliferative neoplasm is sensitive to combined
      targeted inhibition.
AB  - Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone
      marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic
      regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are
      associated with poor outcomes. Here, we showed that combined expression of
      Jak2V617F and mutant IDH1R132H or Idh2R140Q induces MPN progression, alters
      stem/progenitor cell function, and impairs differentiation in mice. Jak2V617F
      Idh2R140Q-mutant MPNs were sensitive to small-molecule inhibition of IDH.
      Combined inhibition of JAK2 and IDH2 normalized the stem and progenitor cell
      compartments in the murine model and reduced disease burden to a greater extent
      than was seen with JAK inhibition alone. In addition, combined JAK2 and IDH2
      inhibitor treatment also reversed aberrant gene expression in MPN stem cells and
      reversed the metabolite perturbations induced by concurrent JAK2 and IDH2
      mutations. Combined JAK2 and IDH2 inhibitor therapy also showed cooperative
      efficacy in cells from MPN patients with both JAK2mut and IDH2mut mutations.
      Taken together, these data suggest that combined JAK and IDH inhibition may offer
      a therapeutic advantage in this high-risk MPN subtype.

PMID- 29355845
TI  - Knee osteoarthritis: when arthroscopy can help
AB  - Arthroscopic surgery of the knee is one of the most common orthopedic procedures
      performed globally. Recently, a lot of attention has been directed towards the
      role of arthroscopic surgery in the setting of osteoarthritis (OA) and its role
      in degenerative knee pathology. A number of recent randomized control trials and
      systematic reviews have suggested limited benefit for arthroscopic surgery and
      partial meniscectomy for this indication. With this recent focus on the use of
      arthroscopy in OA, it is often forgotten that arthroscopy plays an important role
      in the management of other pathologies involving the knee in patients who may
      have a concomitant diagnosis of OA. This evidence-based review highlights
      indications for when arthroscopic intervention is warranted in such patients.

PMID- 29355844
TI  - Endothelial Tie1-mediated angiogenesis and vascular abnormalization promote tumor
      progression and metastasis.
AB  - The endothelial tyrosine kinase receptor Tie1 remains poorly characterized,
      largely owing to its orphan receptor status. Global Tie1 inactivation causes late
      embryonic lethality, thereby reflecting its importance during development. Tie1
      also plays pivotal roles during pathologies such as atherosclerosis and
      tumorigenesis. In order to study the contribution of Tie1 to tumor progression
      and metastasis, we conditionally deleted Tie1 in endothelial cells at different
      stages of tumor growth and metastatic dissemination. Tie1 deletion during primary
      tumor growth in mice led to a decrease in microvessel density and an increase in
      mural cell coverage with improved vessel perfusion. Reduced angiogenesis and
      enhanced vascular normalization resulted in a progressive increase of
      intratumoral necrosis that caused a growth delay only at later stages of tumor
      progression. Concomitantly, surgical removal of the primary tumor decreased the
      number of circulating tumor cells, reduced metastasis, and prolonged overall
      survival. Additionally, Tie1 deletion in experimental murine metastasis models
      prevented extravasation of tumor cells into the lungs and reduced metastatic
      foci. Taken together, the data support Tie1 as a therapeutic target by defining
      its regulatory functions during angiogenesis and vascular abnormalization and
      identifying its role during metastasis.

PMID- 29355843
TI  - Latent HIV reservoirs exhibit inherent resistance to elimination by CD8+ T cells.
AB  - The presence of persistent, latent HIV reservoirs in CD4+ T cells obstructs
      current efforts to cure infection. The so-called kick-and-kill paradigm proposes
      to purge these reservoirs by combining latency-reversing agents with immune
      effectors such as cytotoxic T lymphocytes. Support for this approach is largely
      based on success in latency models, which do not fully reflect the makeup of
      latent reservoirs in individuals on long-term antiretroviral therapy (ART).
      Recent studies have shown that CD8+ T cells have the potential to recognize
      defective proviruses, which comprise the vast majority of all infected cells, and
      that the proviral landscape can be shaped over time due to in vivo clonal
      expansion of infected CD4+ T cells. Here, we have shown that treating CD4+ T
      cells from ART-treated individuals with combinations of potent latency-reversing
      agents and autologous CD8+ T cells consistently reduced cell-associated HIV DNA,
      but failed to deplete replication-competent virus. These CD8+ T cells recognized
      and potently eliminated CD4+ T cells that were newly infected with autologous
      reservoir virus, ruling out a role for both immune escape and CD8+ T cell
      dysfunction. Thus, our results suggest that cells harboring replication-competent
      HIV possess an inherent resistance to CD8+ T cells that may need to be addressed
      to cure infection.

PMID- 29355846
TI  - TimeLapse-seq: adding a temporal dimension to RNA sequencing through nucleoside
      recoding.
AB  - RNA sequencing (RNA-seq) offers a snapshot of cellular RNA populations, but not
      temporal information about the sequenced RNA. Here we report TimeLapse-seq, which
      uses oxidative-nucleophilic-aromatic substitution to convert 4-thiouridine into
      cytidine analogs, yielding apparent U-to-C mutations that mark new transcripts
      upon sequencing. TimeLapse-seq is a single-molecule approach that is adaptable to
      many applications and reveals RNA dynamics and induced differential expression
      concealed in traditional RNA-seq.

PMID- 29355847
TI  - EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor
      antigens.
AB  - We describe a lentivirus-encoded chimeric receptor, termed extracellular vesicle
      (EV)-internalizing receptor (EVIR), which enables the selective uptake of cancer
      cell-derived EVs by dendritic cells (DCs). The EVIR enhances DC presentation of
      EV-associated tumor antigens to CD8+ T cells primarily through MHCI recycling and
      cross-dressing. EVIRs should facilitate exploring the mechanisms and implications
      of horizontal transfer of tumor antigens to antigen-presenting cells.

PMID- 29355848
TI  - Interactome INSIDER: a structural interactome browser for genomic studies.
AB  - We present Interactome INSIDER, a tool to link genomic variant information with
      structural protein-protein interactomes. Underlying this tool is the application
      of machine learning to predict protein interaction interfaces for 185,957 protein
      interactions with previously unresolved interfaces in human and seven model
      organisms, including the entire experimentally determined human binary
      interactome. Predicted interfaces exhibit functional properties similar to those
      of known interfaces, including enrichment for disease mutations and recurrent
      cancer mutations. Through 2,164 de novo mutagenesis experiments, we show that
      mutations of predicted and known interface residues disrupt interactions at a
      similar rate and much more frequently than mutations outside of predicted
      interfaces. To spur functional genomic studies, Interactome INSIDER
      (http://interactomeinsider.yulab.org) enables users to identify whether variants
      or disease mutations are enriched in known and predicted interaction interfaces
      at various resolutions. Users may explore known population variants, disease
      mutations, and somatic cancer mutations, or they may upload their own set of
      mutations for this purpose.

PMID- 29355849
TI  - A whole-animal platform to advance a clinical kinase inhibitor into new disease
      space.
AB  - Synthetic tailoring of approved drugs for new indications is often difficult, as
      the most appropriate targets may not be readily apparent, and therefore few
      roadmaps exist to guide chemistry. Here, we report a multidisciplinary approach
      for accessing novel target and chemical space starting from an FDA-approved
      kinase inhibitor. By combining chemical and genetic modifier screening with
      computational modeling, we identify distinct kinases that strongly enhance ('pro
      targets') or limit ('anti-targets') whole-animal activity of the clinical kinase
      inhibitor sorafenib in a Drosophila medullary thyroid carcinoma (MTC) model. We
      demonstrate that RAF-the original intended sorafenib target-and MKNK kinases
      function as pharmacological liabilities because of inhibitor-induced
      transactivation and negative feedback, respectively. Through progressive
      synthetic refinement, we report a new class of 'tumor calibrated inhibitors' with
      unique polypharmacology and strongly improved therapeutic index in fly and human
      MTC xenograft models. This platform provides a rational approach to creating new
      high-efficacy and low-toxicity drugs.

PMID- 29355850
TI  - Chemical hijacking of auxin signaling with an engineered auxin-TIR1 pair.
AB  - The phytohormone auxin indole-3-acetic acid (IAA) regulates nearly all aspects of
      plant growth and development. Despite substantial progress in our understanding
      of auxin biology, delineating specific auxin response remains a major challenge.
      Auxin regulates transcriptional response via its receptors, TIR1 and AFB F-box
      proteins. Here we report an engineered, orthogonal auxin-TIR1 receptor pair,
      developed through a bump-and-hole strategy, that triggers auxin signaling without
      interfering with endogenous auxin or TIR1/AFBs. A synthetic, convex IAA (cvxIAA)
      hijacked the downstream auxin signaling in vivo both at the transcriptomic level
      and in specific developmental contexts, only in the presence of a complementary,
      concave TIR1 (ccvTIR1) receptor. Harnessing the cvxIAA-ccvTIR1 system, we provide
      conclusive evidence for the role of the TIR1-mediated pathway in auxin-induced
      seedling acid growth. The cvxIAA-ccvTIR1 system serves as a powerful tool for
      solving outstanding questions in auxin biology and for precise manipulation of
      auxin-mediated processes as a controllable switch.

PMID- 29355851
TI  - Fresh from the biotech pipeline-2017.

PMID- 29355853
TI  - Microbiome: Gut microbiota sways response to cancer immunotherapy.

PMID- 29355852
TI  - Drug resistance in Plasmodium.
AB  - A marked decrease in malaria-related deaths worldwide has been attributed to the
      administration of effective antimalarials against Plasmodium falciparum, in
      particular, artemisinin-based combination therapies (ACTs). Increasingly, ACTs
      are also used to treat Plasmodium vivax, the second major human malaria parasite.
      However, resistance to frontline artemisinins and partner drugs is now causing
      the failure of P. falciparum ACTs in southeast Asia. In this Review, we discuss
      our current knowledge of markers and mechanisms of resistance to artemisinins and
      ACTs. In particular, we describe the identification of mutations in the propeller
      domains of Kelch 13 as the primary marker for artemisinin resistance in P.
      falciparum and explore two major mechanisms of resistance that have been
      independently proposed: the activation of the unfolded protein response and
      proteostatic dysregulation of parasite phosphatidylinositol 3- kinase. We
      emphasize the continuing challenges and the imminent need to understand
      mechanisms of resistance to improve parasite detection strategies, develop new
      combinations to eliminate resistant parasites and prevent their global spread.

PMID- 29355855
TI  - Retentive Force of Zirconia Implant Crowns on Titanium Bases Following Different
      Surface Treatments.
AB  - PURPOSE: Screw-retained zirconia implant crowns with an internal titanium base
      have favorable mechanical properties compared with single-piece zirconia implant
      crowns; however, the screw-retained implant crowns require adequate bonding
      between the zirconia crown and the titanium base. This study measured the
      retention between a titanium base and a full-contour zirconia implant crown
      following different surface treatments of their bonded surfaces. MATERIALS AND
      METHODS: Full-contour screw-retained zirconia implant crowns were fabricated to
      fit a titanium base. The crowns were bonded to the titanium bases following one
      of four treatment protocols (n = 15 per protocol group): no surface treatment
      (Control), 10-methacryloyloxydecyl dihydrogen phosphate (MDP) primer on the
      intaglio of crown and exterior of base (MDP), alumina airborne-particle abrasion
      of the intaglio of crown and exterior of base (Alu), and alumina airborne
      particle abrasion and an MDP primer on the intaglio of crown and exterior of base
      (Alu+MDP). All crowns were bonded to the base with resin cement. Specimens were
      stored in water for 24 hours at 37 degrees C and then thermocycled in water, with
      a temperature range of 5 degrees C to 55 degrees C, for 15,000 cycles with a 15
      second dwell time. Crowns were separated from the titanium bases using a
      universal testing machine. The four treatment protocols were compared using one
      way analysis of variance (ANOVA), followed by Tukey post hoc tests (P < .05).
      Sectioned specimens were examined with scanning electron microscopy (SEM).
      RESULTS: Retention forces for Control (737.8 +/- 148.9 N) and MDP (804.1 +/-
      114.5 N) were significantly greater than Alu+MDP (595.5 +/- 122.2 N), which was
      significantly greater than Alu (428.2 +/- 93.8 N). Visual inspection of the
      debonded specimens showed that the majority of the cement remnants were seen on
      the external surface of the titanium bases. Microscopic examination of the
      interface between the crown and the unaltered base shows that the cement gap is
      approximately 13 MUm at the crest of the microgrooves and 50 MUm within the
      channel of the microgrooves. After airborne-particle abrasion, the microgrooves
      became significantly dulled, and the cement gap increased to 27 to 40 MUm at the
      crest and 55 to 58 MUm in the channels. CONCLUSION: Airborne-particle abrasion of
      titanium bases that contain retentive microgrooves prior to bonding is
      contraindicated. Application of an MDP primer demonstrated limited improvement in
      the retention of the zirconia implant crowns.

PMID- 29355856
TI  - Bone Graft and Substitutes Associated with Titanium Dome for Vertical Bone
      Formation in Osseointegrated Implants: Histomorphometric Analysis in Dogs.
AB  - PURPOSE: This animal study investigated vertical bone formation (VBF) around
      implants and used histomorphometric analysis to compare different bone-filling
      materials associated with a massive titanium dome as a tissue barrier. MATERIALS
      AND METHODS: Seven dogs were submitted to surgical procedures with extraoral
      access to the lower edge of the mandible, and four implants were semi-inserted in
      each animal. Each implant received one treatment: autogenous bone with clot (AB),
      control clot (C), synthetic graft (Biogran [BG]), or xenograft (Bio-Oss [BO]).
      Massive titanium domes were stabilized over the implants. Histologic analysis was
      performed after 3 months, and quantitative aspects were evaluated in extraosseous
      and intraosseous threads on Image Pro-Plus software. RESULTS: VBF around implants
      exhibited significant values in AB compared with other groups. BG and BO
      presented statistical equivalency to AB and C in the apposition and filling of
      extraosseous threads. There was no difference between groups for parameters
      evaluated in intraosseous threads. CONCLUSION: The experimental model was valid
      for evaluation of VBF around implants placed in atrophic mandibles. Considering
      the limitations of this study, histomorphometric analysis evidenced better
      outcomes for group AB. Even though groups BG and BO presented worse outcomes than
      AB, they were slightly better compared with the control group.

PMID- 29355857
TI  - Stepwise chelation-etching synthesis of carbon-confined ultrafine SnO2
      nanoparticles for stable sodium storage.
AB  - A stepwise chelation-etching approach to synthesize carbon-confined ultrafine
      SnO2 nanoparticles was developed via conformal coating with polydopamine and
      chelation-etching with ethylenediaminetetraacetic acid (EDTA). EDTA plays a
      crucial role in the ordered removal of cobalt and tin. The obtained composite
      exhibits superior sodium storage performance.

PMID- 29355854
TI  - Prokaryotic cytoskeletons: protein filaments organizing small cells.
AB  - Most, if not all, bacterial and archaeal cells contain at least one protein
      filament system. Although these filament systems in some cases form structures
      that are very similar to eukaryotic cytoskeletons, the term 'prokaryotic
      cytoskeletons' is used to refer to many different kinds of protein filaments.
      Cytoskeletons achieve their functions through polymerization of protein monomers
      and the resulting ability to access length scales larger than the size of the
      monomer. Prokaryotic cytoskeletons are involved in many fundamental aspects of
      prokaryotic cell biology and have important roles in cell shape determination,
      cell division and nonchromosomal DNA segregation. Some of the filament-forming
      proteins have been classified into a small number of conserved protein families,
      for example, the almost ubiquitous tubulin and actin superfamilies. To understand
      what makes filaments special and how the cytoskeletons they form enable cells to
      perform essential functions, the structure and function of cytoskeletal molecules
      and their filaments have been investigated in diverse bacteria and archaea. In
      this Review, we bring these data together to highlight the diverse ways that
      linear protein polymers can be used to organize other molecules and structures in
      bacteria and archaea.

PMID- 29355858
TI  - Water-induced formation of a chiral phenylalanine derivative supramolecule.
AB  - In biological systems, chiral self-assemblies are formed in water. To understand
      the role of water in the formation of supramolecular chirality, an amino acid
      derivative, N,N-diphenylalanine-3,4,9,10-perylenetetracarboxylicdiimide (PBI
      Phe), was synthesized from perylene-3,4,9,10-tetracarboxylic dianhydride and
      phenylalanine. PBI-Phe self-assembled into a spherical structure in pure DMSO,
      but into a helical fiber structure in a solution of DMSO mixed with water.
      Furthermore, increasing the relative amount of water included in the solution led
      to an increase the supramolecular chirality.

PMID- 29355859
TI  - Enantioselective cooperative proton-transfer catalysis using chiral ammonium
      phosphates.
AB  - Chiral phosphorate anions are shown to be highly enantioselective templates for
      proton-transfer catalysis. A salt generated in situ from a bridgehead amine and a
      BINOL-derived chiral phosphoric acid serves as an effective proton-shuttle that
      exhibits remarkable enantioselectivity in a bioinspired, triple co-operative
      catalysis involving an achiral NHC. Thioesters with a beta-chiral center can be
      prepared in a single step from substituted cinnamaldehyde derivatives, with up to
      99% yield and 99% ee. Heteroaryl groups are well tolerated in these reactions,
      despite the presence of basic sites.

PMID- 29355860
TI  - Interface engineered in situ anchoring of Co9S8 nanoparticles into a multiple
      doped carbon matrix: highly efficient zinc-air batteries.
AB  - Interface modification is an effective and promising route for developing
      functional electrocatalysts. However, researchers have not created a reliable
      method to optimize the interfaces of components existing in electrocatalysts,
      although it is very crucial for the technological development of high-performance
      electrodes. Here, we develop a strategy aiming at the in situ anchorage of Co9S8
      nanoparticles into a nitrogen (N), sulfur (S) co-implanted three-dimensional
      carbon matrix (Co9S8@NSCM) as a highly active and durable nonprecious metal
      electrocatalyst for the oxygen reduction reaction (ORR) and oxygen evolution
      reaction (OER) in alkaline medium. This strategy offers an opportunity to
      optimize the interface interaction and affords high activity for the ORR and OER
      in terms of low overpotentials and high current intensities. In addition, by
      confining Co9S8 nanoparticles into a N,S-doped carbon matrix, corrosion and
      aggregation can be effectively prevented, and thus the catalyst exhibits nearly
      unfading ORR catalytic performance after 100 000 s testing, a low discharge
      charge voltage gap (0.81 V) and a long cycle life (up to 840 cycles) in Zn-air
      batteries. The present work highlights potentially powerful interface engineering
      for designing multi-component heterostructures with advanced performances in
      oxygen electrochemistry and related energy conversion.

PMID- 29355861
TI  - Antibacterial nitric oxide- and singlet oxygen-releasing polystyrene
      nanoparticles responsive to light and temperature triggers.
AB  - Novel therapies to prevent bacterial infections are of utmost importance in
      biomedical research due to the emergence of multidrug-resistant strains of
      bacteria. Herein, we report the preparation, characterization and antibacterial
      evaluation of sulfonated polystyrene nanoparticles simultaneously releasing two
      antibacterial species, nitric oxide (NO) and singlet oxygen (O2(1Deltag)), upon
      irradiation with visible light. The nanoparticles were prepared by simple and
      scalable processes from nanofiber membranes with an encapsulated NO photodonor
      and/or ionically entangled tetracationic porphyrin/phthalocyanine
      photosensitizers. The release of NO and O2(1Deltag) from the polystyrene
      nanoparticles is controlled by light wavelength and dose, as well as by
      temperature, which influences the diffusion coefficient and solubility of both
      species in the polystyrene matrix. The concentrations of NO and O2(1Deltag) were
      measured by amperometric and time-resolved spectroscopic techniques and by
      chemical analysis. Due to the efficient photogeneration of both species at
      physiological temperature and resultant strong antibacterial action observed on
      Escherichia coli, the nanoparticles are a promising material for antibacterial
      applications triggered/modulated by light and temperature.

PMID- 29355862
TI  - UV-driven overall water splitting using unsupported gold nanoparticles as
      photocatalysts.
AB  - We confirmed that Au nanoparticles (>10 nm) exhibit photocatalytic overall water
      splitting into H2 and O2 simultaneously with a ratio close to 2 : 1 without the
      assistance of sacrificial electron donors and cocatalysts under UV illumination
      for the first time. The hydrogen production rate of 5.7 MUmol g-1 h-1 in pure
      water was achieved, which is higher than that of TiO2 nanoparticles (P25, 1.2
      MUmol g-1 h-1). The interband transitions from 5d (valence band) to 6sp
      (conduction band) are responsible for this photocatalytic activity over Au
      nanoparticles.

PMID- 29355863
TI  - Anionic merocyanine dyes based on thiazol-2-hydrazides: reverse solvatochromism,
      preferential solvation and multiparametric approaches to spectral shifts.
AB  - Anionic merocyanine colored dyes based on (4-nitro/cyanophenyl)-substituted
      thiazol-2-hydrazides (THAs), which are donor-pi-acceptor type push-pull molecular
      systems and characterized with a strong intramolecular charge transfer (ICT) in
      the ground state, have been examined as reverse solvatochromic systems. THAs are
      shown to exhibit both positive and negative solvatochromism with a reversal of
      the latter occurring for solvents of ET(30) value of ca. 45. The observed
      behavior is traceable to relative contributions of benzenoid and quinonoid
      resonance forms of the THAs and their stabilization by solvents to different
      degrees. Solvatochromic studies in binary mixtures of polar aprotic and protic
      solvents reveal that the latter are always preferred in the solvation microsphere
      of THAs. Multiparametric treatment of the ET(dye) parameters by Catalan and
      Kamlet-Taft linear solvation energy relationships (LSERs) compellingly bears out
      the remarkable influence of hydrogen-bond donating (HBD) acidity, dipolarity and
      polarizability of the media on the spectral properties of the anionic dyes;
      hydrogen-bond accepting (HBA) basicity of the solvents is found to influence the
      least.

PMID- 29355864
TI  - Modulation of the carrier mobility enhancement in Si/Ge core-shell nanowires
      under different interface confinements.
AB  - The theoretical analysis of the effect of interface confinement on the
      enhancement of carrier mobility in Si nanowires (SiNWs) is one of the critical
      aspects in the design and development of high efficiency Si-based optoelectronic
      devices. Herein, we propose an analytical method for SiNWs under different
      interface confinements in terms of the atomic-bond-relaxation correlation
      mechanism and continuum medium mechanics. Moreover, an analytical expression for
      the relationship between carrier mobility and bond identities is derived and the
      results are validated with the related experimental measurements. It is found
      that the size reduction of SiNWs can not only increase the energy bandgap, but
      also enhance the phonon and surface roughness scattering, thereby allowing for
      the depression of carrier mobility. Moreover, the underlying mechanism regarding
      the temperature dependent-carrier mobility in SiNWs with different orientations
      embedded within Ge coating layers is clarified, which provides a pathway to
      modulate the transport properties in Si-based nanostructures for desirable
      applications.

PMID- 29355865
TI  - Droplet microfluidic SANS.
AB  - The coupling of droplet microfluidics and Small Angle Neutron Scattering (SANS)
      is demonstrated with a range of model systems: isotopic solvent (H2O/D2O)
      mixtures, surfactant (sodium dodecyl sulfate, SDS) solutions and colloidal
      (silica) suspensions. Several droplet carrier phases are evaluated and
      fluorinated oil emerges as a suitable fluid with minimal neutron background
      scattering (commensurate with air), and excellent interfacial properties. The
      combined effects of flow dispersion and compositional averaging caused by the
      neutron beam footprint are evaluated in both continuous and droplet flows and an
      operational window is established. Systematic droplet-SANS dilution measurements
      of colloidal silica suspensions enable unprecedented quantification of form and
      structure factors, osmotic compressibility, enhanced by constrained global data
      fits. Contrast variation measurements with over 100 data points are readily
      carried out in 10-20 min timescales, and validated for colloidal silica of two
      sizes, in both continuous and droplet flows. While droplet microfluidics is
      established as an attractive platform for SANS, the compositional averaging
      imposed by large (~1 cm) beam footprints can, under certain circumstances, make
      single phase, continuous flow a preferable option for low scattering systems. We
      propose simple guidelines to assess the suitability of either approach based on
      well-defined system parameters.

PMID- 29355866
TI  - Optimum morphology of gold nanorods for light-induced hyperthermia.
AB  - Owing to their unique chemical and physical properties, colloidal gold
      nanoparticles have prompted a wide variety of biocompatible nano-agents for
      cancer imaging, diagnosis and treatment. In this context, biofunctionalized gold
      nanorods (AuNRs) are promising candidates for light-induced hyperthermia, to
      cause local and selective damage in malignant tissue. Yet, the efficacy of AuNR
      based hyperthermia is highly dependent on several experimental parameters; in
      particular, the AuNR morphology strongly affects both physical and biological
      processes. In the present work, we systematically study the influence of
      different structural parameters like the AuNR aspect ratio, length and molecular
      weight on in vitro cytotoxicity, cellular uptake and heat generation efficiency.
      Our results enable us to identify the optimum AuNR morphology to be used for in
      vivo hyperthermia treatment.

PMID- 29355867
TI  - Hydrogen-bond strength changes network dynamics in associating telechelic PDMS.
AB  - Associating polymers are a class of materials with widely tunable macroscopic
      properties. Here, we investigate telechelic poly(dimethylsiloxanes) of several
      molecular weights (MW) with different hydrogen bonding end groups. Besides the
      well-established increase of the glass transition temperature Tg with decreasing
      MW, Tg remains unchanged as the end group varies from NH2 over OH to COOH. For
      the latter system, a 2nd Tg is found which indicates a segregated phase. In
      contrast, rheological measurements reveal a qualitative difference in the
      viscoelastic response of NH2-terminated and COOH-terminated chains. Both systems
      show clear signs of end group association, but only the latter exhibits an
      extended rubbery plateau. All features observed in the rheology experiments have
      corresponding processes in the dielectric measurements. This provides insight
      into the underlying molecular mechanisms, and especially reveals that many end
      groups of the COOH-terminated chains phase segregate while a certain fraction
      forms binary associates and remains non-segregated. In contrast, the NH2
      terminated systems form only binary associates increasing the effective chain
      length, whereas the COOH-terminated system consists of two types of associates
      forming a crosslinked network. Remarkably, a single species of end group forms
      two qualitatively different types of associates: transient bonds which allow
      stress release by a bond-partner exchange mechanism, and effectively permanent
      bonds formed by a phase segregated fraction of end groups which are stable on the
      timescale of the transient mechanism.

PMID- 29355868
TI  - A new mechanism for internal nucleophilic substitution reactions.
AB  - A new mechanism for the classic internal nucleophilic substitution reactions SNi
      by means of computational studies in the gas-phase, DCM and acetonitrile is
      reported. Despite the importance of the SNi mechanism, since the mid-1990s this
      mechanism has remained unexplored. This study focused mainly on the comparison
      between the mechanisms postulated to date for the SNi reactions and a new
      mechanism suggested by us that fits better the experimental observations. This
      comparative study has been applied to the conversion of ethyl, neopentyl,
      isopropyl and tert-butyl chlorosulfites into the corresponding alkyl chlorides.
      This new mechanism occurs through two transition structures. For primary and
      secondary substrates, the first transition structure is a 6-center syn
      rearrangement of the alkanesulfonyl chloride that produces the corresponding
      olefin by simultaneous expulsion of HCl and SO2. The olefin, HCl and SO2 form a
      molecular complex. The final syn-addition of HCl to the olefin leads to alkyl
      chloride with the retention of configuration. For tertiary substrates, a
      variation of the previous mechanism is postulated with the intervention of
      contact ion pairs. It is of great importance to emphasize that this new mechanism
      is able to explain some experimental observations such as the presence of olefins
      in these types of reactions and the low reactivity of some systems such as
      neopentyl chlorosulfite. Our results pave the way to a new mechanistic
      perspective in similar reactions which will need further studies and validation.

PMID- 29355869
TI  - Gold nanorods decorated with a cancer drug for multimodal imaging and therapy.
AB  - Cancer, a condition with uncontrolled cell division, is the second leading cause
      of death worldwide. The currently available techniques for the imaging and
      treatment of cancer have their own limitations and hence a combination of more
      than one modality is expected to increase the efficacy of both diagnosis and
      treatment. In the present study, we have developed a multimodal imaging and
      therapeutic system by incorporating a chemotherapeutic drug, mitoxantrone (MTX)
      onto PEG coated gold nanorods (GNR). Strong absorption in the near-infrared (NIR)
      and visible regions qualifies GNR as an efficient photothermal (PTT) agent upon
      irradiation with either a NIR or visible laser. Additionally, the enhanced
      electric field of GNR makes it a suitable substrate for surface enhanced Raman
      scattering (SERS). Modification of GNR with amino PEG offers biocompatibility
      without affecting its optical property. In order to achieve tumor specificity,
      GNR-PEG was conjugated with tumor specific marker that can target cancer cells,
      leaving the normal cells unaffected. The incorporation of fluorescent
      chemotherapeutic drug mitoxantrone onto GNR-PEG facilitates chemotherapy as well
      as fluorescence imaging. The therapeutic efficacy of the developed GNR based
      system is tracked using fluorescence imaging and Raman imaging. The careful
      design of the system also facilitates the controlled release of the drug by
      photothermal triggering. Likewise, the imaging modality could be chosen as either
      Raman or fluorescence to monitor drug release in accordance with irradiation. The
      physico-chemical properties, and drug release profiles under different
      physiological conditions have been well studied. Finally, the developed system
      was tested for its therapeutic efficacy using cancer cells, in vitro. The
      receptor mediated cell uptake was more effective in folate receptor over
      expressing cancer cells than in the normal and low-expressing cells. Accordingly
      the percentage of cell death was higher in folate receptor over-expressing cancer
      cells, which was further enhanced due to the effect of the dual therapeutic
      approach. The cell uptake and treatment efficacy was monitored using fluorescence
      microscopy and SERS. In conclusion, the developed GNR-PEG-MTX system is found to
      be an efficient multimodal therapeutic agent against cancer which could be
      tracked using two different techniques.

PMID- 29355872
TI  - A silencing-mediated enhancement of osteogenic differentiation by supramolecular
      ternary siRNA polyplexes comprising biocleavable cationic polyrotaxanes and
      anionic fusogenic peptides.
AB  - Gene silencing of noggin by small interfering RNA (siRNA) is a promising approach
      for the treatment of bone defects, because noggin deactivates bone morphogenetic
      protein-2 (BMP-2) and suppresses osteogenic differentiation. Here, we
      demonstrated the silencing of the noggin gene by siRNA polyplexes composed of
      noggin-targeted siRNA and biocleavable cationic polyrotaxanes (DMAE-SS-PRX). To
      improve the endosomal escape efficiencies of the DMAE-SS-PRX/siRNA polyplexes,
      anionic and fusogenic GALA peptides were integrated onto the DMAE-SS-PRX/siRNA
      polyplexes via simple electrostatic interactions. The formation of ternary
      complexes was confirmed by gel electrophoresis, dynamic light scattering, and
      zeta-potential measurements. Although the association of GALA peptides with the
      DMAE-SS-PRX/siRNA polyplexes did not remarkably affect the cellular uptake
      efficiency of siRNA, the endosomal escape efficiency was remarkably increased for
      GALA/DMAE-SS-PRX/siRNA ternary polyplexes because of the endosomal and lysosomal
      membrane destabilization by GALA peptides. Consequently, GALA/DMAE-SS-PRX/siRNA
      ternary polyplexes showed significantly higher gene silencing efficiency against
      noggin and enhanced the BMP-2-mediated osteogenic differentiation efficiency.
      Therefore, we concluded that GALA/DMAE-SS-PRX/siRNA ternary polyplexes can be
      effective siRNA carriers for suppressing the expression of specific endogenous
      genes. Consequently, we believe that a more practical approach in vivo will be
      the combined use of BMP-2 and GALA/DMAE-SS-PRX/siRNA ternary polyplexes, because
      it will improve the efficacy of bone regeneration therapy.

PMID- 29355873
TI  - Chiral phosphoric acid catalysis: from numbers to insights.
AB  - Chiral phosphoric acids (CPAs) have emerged as powerful organocatalysts for
      asymmetric reactions, and applications of computational quantum chemistry have
      revealed important insights into the activity and selectivity of these catalysts.
      In this tutorial review, we provide an overview of computational tools at the
      disposal of computational organic chemists and demonstrate their application to a
      wide array of CPA catalysed reactions. Predictive models of the stereochemical
      outcome of these reactions are discussed along with specific examples of
      representative reactions and an outlook on remaining challenges in this area.

PMID- 29355875
TI  - Sky-blue emitting bridged diiridium complexes: beneficial effects of
      intramolecular pi-pi stacking.
AB  - The potential of intramolecular pi-pi interactions to influence the photophysical
      properties of diiridium complexes is an unexplored topic, and provides the
      motivation for the present study. A series of diarylhydrazide-bridged diiridium
      complexes functionalised with phenylpyridine (ppy)-based cyclometalating ligands
      is reported. It is shown by NMR studies in solution and single crystal X-ray
      analysis that intramolecular pi-pi interactions between the bridging and
      cyclometalating ligands rigidify the complexes leading to high luminescence
      quantum efficiencies in solution and in doped films. Fluorine substituents on the
      phenyl rings of the bridge promote the intramolecular pi-pi interactions.
      Notably, these non-covalent interactions are harnessed in the rational design and
      synthesis of the first examples of highly emissive sky-blue diiridium complexes
      featuring conjugated bridging ligands, for which they play a vital role in the
      structural and photophysical properties. Experimental results are supported by
      computational studies.

PMID- 29355876
TI  - Measurement of Nursing Home Culture Change: Systematic Review.
AB  - Nursing home culture change (NHCC) aims to change the way care is provided in
      nursing homes. Valid and reliable measures are needed to evaluate the impact of
      NHCC on outcomes. The current systematic review provides an overview of
      instruments designed to measure NHCC and criteria for others to evaluate and
      choose instruments according to their own purpose. Ten instruments were
      identified that measure NHCC on an organizational level. Lack of development
      description hindered their assessment, and studies examining the relationship
      between NHCC and outcomes are rare. A common limitation of the instruments
      reviewed was the lack of psychometric testing; thus, their validity and
      reliability need further exploration. [Res Gerontol Nurs. 2018; 11(2):103-112.].

PMID- 29355877
TI  - Emergency Department Use by Community-Dwelling Individuals With Dementia in the
      United States: An Integrative Review.
AB  - As part of the National Plan to Address Alzheimer's Disease, reducing potentially
      avoidable emergency department (ED) use by individuals with dementia has been
      identified as a component of enhancing the quality and efficiency of care for
      this population. To help inform the development of interventions to achieve this
      goal, an integrative review was conducted to: (a) compare rates and reasons for
      ED visits by community-dwelling individuals with and without dementia,
      considering also the effect of dementia subtype and severity; and (b) identify
      other risk factors for increased ED use among community-dwelling individuals with
      dementia. Nineteen articles met inclusion criteria. Individuals with dementia had
      higher rates of ED visits compared to those without dementia, although
      differences were attenuated in the last year of life. Increased symptoms and
      disability were associated with increased rates of ED visits, whereas resources
      that enabled effective management of increased need decreased rates.
      Gerontological nurses across settings are on the frontlines of preventing
      potentially avoidable ED visits by community-dwelling individuals with dementia
      through patient and family education and leadership in the development of new
      models of care. [Journal of Gerontological Nursing, 44(3), 23-30.].

PMID- 29355878
TI  - Negotiating Risky Preferences in Nursing Homes: A Case Study of the Rothschild
      Person-Centered Care Planning Approach.
AB  - Delivering person-centered care (PCC) is no longer an option for nursing homes
      (NH) that receive funding from the Centers for Medicare & Medicaid Services. NH
      staff need evidence-based protocols to guide efforts in honoring preferred
      choices of residents, especially those that are perceived to be risky. The
      Rothschild Care Planning Process for Resident Choice was created to honor such
      choices. The current article provides a case exemplar to demonstrate the use of
      the Rothschild Care Planning Process for Resident Choice with one NH resident who
      was perceived by staff to be making a risky choice. The scenario outlines six
      steps to the process, highlighting areas for focus and documentation that
      addresses complexities and best practices in delivering PCC. Three
      recommendations are offered to address residents' choices that carry risk: (a)
      adapt care community policies, (b) engage direct care staff in care planning, and
      (c) provide staff training in facilitating resident choice. [Journal of
      Gerontological Nursing, 44(8), 11-17.].

PMID- 29355879
TI  - Influence of Teamwork on Health Care Workers' Perceptions About Care Delivery and
      Job Satisfaction.
AB  - The aim of the current study was to examine the nature of teamwork in care
      facilities and its impact on the effectiveness of care delivery to older adults
      and job satisfaction among health care workers. A focused ethnography was
      conducted at two care facilities where older adults reside. Analysis of
      interviews with 22 participants revealed perceptions of teamwork and
      understandings about facilitators of and barriers to effective teamwork.
      Participants indicated that team relationships impacted care provided and job
      satisfaction. Participants also identified trust and reciprocity, communication,
      and sharing a common goal as critical factors in effective teamwork. In addition,
      participants identified the role of management as important in setting the tone
      for teamwork. Future research is needed to understand the complexity of
      supporting teamwork in residential settings given the challenges of culture,
      diversity, and individuals working multiple jobs. [Journal of Gerontological
      Nursing, 44(4), 37-44.].

PMID- 29355880
TI  - Dying Behind Bars.

PMID- 29355883
TI  - Optimizing Pain Management Through Opioid Deprescribing.
AB  - The use of opioid drug therapy in older adults has increased over the past
      decade. Although use of opioid drugs may be clinically warranted, ongoing use
      needs to be monitored closely to evaluate risks and benefits, especially with the
      potential for adverse events and misuse. An opioid drug deprescribing protocol
      would provide clinicians with a method to assess an individual's need for opioid
      agents, as well as a systematic process to taper opioid drug therapy when deemed
      appropriate. Although more than 60 studies have reported methods for
      deprescribing, there is currently no established guideline for discontinuing
      opioid medications. The U.S. Department of Veterans Affairs has developed an
      algorithm to assist clinicians with opioid drug discontinuation decision making.
      As efforts to discontinue opioid drugs for chronic non-cancer pain in older
      adults continue to expand, nurses, as an integral part of the inter-professional
      team, will play a key role in monitoring and assessing patients' pain and care
      plans. [Journal of Gerontological Nursing, 44(1), 9-14.].

PMID- 29355885
TI  - As Part of a New National Emergency Department Collaborative, the AGS & Partners
      Aim for Better Outcomes at Lower Costs.

PMID- 29355884
TI  - Developing a Serious Game for Nurse Education.
AB  - Future nursing education is challenged to develop innovative and effective
      programs that align with current changes in health care and to educate nurses
      with a high level of clinical reasoning skills, evidence-based knowledge, and
      professional autonomy. Serious games (SGs) are computer-based simulations that
      combine knowledge and skills development with video game-playing aspects to
      enable active, experiential, situated, and problem-based learning. In a PhD
      project, a video-based SG was developed to teach nursing students nursing care
      for patients with chronic obstructive pulmonary disease in home health care and
      hospital settings. The current article summarizes the process of the SG
      development and evaluation. [Journal of Gerontological Nursing, 44(1), 15-19.].

PMID- 29355886
TI  - Antidepressants for depression in adults with HIV infection.
AB  - BACKGROUND: Rates of major depression among people living with HIV (PLWH) are
      substantially higher than those seen in the general population and this may
      adversely affect antiretroviral treatment outcomes. Several unique clinical and
      psychosocial factors may contribute to the development and persistence of
      depression in PLWH. Given these influences, it is unclear if antidepressant
      therapy is as effective for PLWH as the general population. OBJECTIVES: To assess
      the efficacy of antidepressant therapy for treatment of depression in PLWH.
      SEARCH METHODS: We searched The Cochrane Common Mental Disorders Group's
      specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a
      cited reference search on the Web of Science for reports of all included studies.
      We conducted additional searches of the international trial registers including;
      ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV
      and AIDS - Clinical trials register. We searched grey literature and reference
      lists to identify additional studies and contacted authors to obtain missing
      data. We applied no restrictions on date, language or publication status to the
      searches, which included studies conducted between 1 January 1980 and 18 April
      2017. SELECTION CRITERIA: We included randomized controlled trials of
      antidepressant drug therapy compared to placebo or another antidepressant drug
      class. Participants eligible for inclusion had to be aged 18 years and older,
      from any setting, and have both HIV and depression. Depression was defined
      according to Diagnostic and Statistical Manual of Mental Disorders or
      International Statistical Classification of Diseases criteria. DATA COLLECTION
      AND ANALYSIS: Two review authors independently applied the inclusion criteria and
      extracted data. We presented categorical outcomes as risk ratios (RR) with 95%
      confidence intervals (CIs). Continuous outcomes were presented mean (MD) or
      standardized mean differences (SMD) with standard deviations (SD). We assessed
      quality of evidence using the GRADE approach. MAIN RESULTS: We included 10
      studies with 709 participants in this review. Of the 10 studies, eight were
      conducted in high income countries (USA and Italy), seven were conducted prior to
      2000 and seven had predominantly men. Seven studies assessed antidepressants
      versus placebo, two compared different antidepressant classes and one had three
      arms comparing two antidepressant classes with placebo.Antidepressant therapy may
      result in a greater improvement in depression compared to placebo. There was a
      moderate improvement in depression when assessed with the Hamilton Depression
      Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to
      0.96; participants = 357; studies = 6; I2 = 62%, low quality evidence). However,
      there was no evidence of improvement when this was assessed with HAM-D score as a
      dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies =
      5; I2 = 0%, low quality evidence) or Clinical Global Impression of Improvement
      (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I2
      = 29%, low quality evidence). There was little to no difference in the proportion
      of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants
      = 306; studies = 4; I2 = 0%, moderate quality evidence).The methods of reporting
      adverse events varied substantially between studies, this resulted in very low
      quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21;
      participants = 167; studies = 2; I2 = 34%; very low quality evidence). Based on
      this, we were unable to determine if there was a difference in the proportion of
      participants experiencing adverse events in the antidepressant versus placebo
      arms. However, sexual dysfunction was reported commonly in people receiving
      selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic
      antidepressants (TCAs) frequently reported anticholinergic adverse effects such
      as dry mouth and constipation. There were no reported grade 3 or 4 adverse events
      in any study group.There was no evidence of a difference in follow-up CD4 count
      at study termination (MD -6.31 cells/mm3, 95% CI -72.76 to 60.14; participants =
      176; studies = 3; I2 = 0%; low quality evidence). Only one study evaluated
      quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies
      = 1; very low quality evidence), due to the poor quality evidence we could not
      draw conclusions for this outcome.There were few studies comparing different
      antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to
      improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to
      4.47; participants = 14; studies = 1; very low quality evidence). There was some
      evidence that mirtazapine resulted in a greater improvement in depression
      compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies =
      1; low quality evidence); however, this finding was not consistent for all
      measures of improvement in depression for this comparison.No studies reported on
      virological suppression or any other HIV specific outcomes.The studies included
      in this review had an overall unclear or high risk of bias due to under-reporting
      of study methods, high risk of attrition bias and inadequate sequence generation
      methods. Heterogeneity between studies and the limited number of participants,
      and events lead to downgrading of the quality of the evidence for several
      outcomes. AUTHORS' CONCLUSIONS: This review demonstrates that antidepressant
      therapy may be more beneficial than placebo for the treatment of depression in
      PLWH. The low quality of the evidence contributing to this assessment and the
      lack of studies representing PLWH from generalized epidemics in low- to middle
      income countries make the relevance of these finding in today's context limited.
      Future studies that evaluate the effectiveness of antidepressant therapy should
      be designed and conducted rigorously. Such studies should incorporate evaluation
      of stepped care models and health system strengthening interventions in the study
      design. In addition, outcomes related to HIV care and antiretroviral therapy
      should be reported.

PMID- 29355887
TI  - Accuracy of fetal fibronectin for assessing preterm birth risk in asymptomatic
      pregnant women: a systematic review and meta-analysis.
AB  - INTRODUCTION: Fetal fibronectin (fFN) is a validated test for assessing risk of
      preterm birth for women presenting with symptoms. Our aim was to evaluate the
      accuracy of fFN to detect the risk of preterm birth in asymptomatic women.
      MATERIAL AND METHODS: Searches were conducted to identify studies where fFN was
      performed in asymptomatic women beyond 22 weeks' gestation. EMBASE, MEDLINE,
      CINHAL, AMED and BNI were searched between 2005 and 2017. Studies before 2005
      were identified from a published systematic review. Women were grouped as
      singleton pregnancies, with and without risk factors for preterm birth, and
      multiple pregnancy. Quality assessment was performed using QUADAS-2. When
      possible, data were pooled using a hierarchical, bivariate random effects model.
      RESULTS: Fifteen studies met the inclusion criteria: six studies of singleton
      pregnancies in women without risk factors (1236 women), four in women with risk
      factors for preterm birth (2628 women) and five studies were of multiple
      pregnancy (1427 women). The pooled sensitivity and specificity of fFN in "no risk
      factors singletons" were 0.48 (95% CI 0.20-0.77), and 0.96 (95% CI 0.86-0.99),
      respectively. The likelihood ratio of a positive test result was 12 (95% CI 4.70
      30.68). The pooled sensitivity and specificity of fFN in "risk factors
      singletons" were 0.34 (95% CI 0.24-0.43), and 0.91 (95% CI 0.88-0.93). The
      accuracy of fFN in multiple pregnancies was inconclusive. CONCLUSION: Our
      findings suggest in asymptomatic singleton pregnancies without risk factors, a
      positive fFN result indicates a large shift from pre- to post-test probability,
      possibly identifying women at increased risk of preterm birth.

PMID- 29355888
TI  - Association of microRNA-200c expression levels with clinicopathological factors
      and prognosis in endometrioid endometrial cancer.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are regulators of gene expression, which play an
      important role in many critical cellular processes including apoptosis,
      proliferation and cell differentiation. Aberrant miRNA expression has been
      reported in a variety of human malignancies. Therefore, miRNAs may be potentially
      used as cancer biomarkers. miRNA-200c, which is a member of the miRNA-200 family,
      might play an essential role in tumor progression. The purpose of this study was
      to evaluate the prognostic and clinical significance of miRNA-200c in women with
      endometrioid endometrial cancer. MATERIAL AND METHODS: Total RNA extraction from
      90 archival formalin-fixed paraffin-embedded tissue samples of endometri-oid
      endometrial cancer and 10 normal endometrium samples was performed. After cDNA
      synthesis, real-time polymerase chain reaction was conducted and relative
      expression of miRNA-200c was assessed. Then, miRNA-200c expression levels were
      evaluated with regard to clinicopathological characteristics. RESULTS: The
      expression levels of miRNA-200c were significantly increased in endometrioid
      endometrial cancer samples. Expression of miRNA-200c maintained at significantly
      higher levels in the early stage endometrioid endometrial cancer compared with
      more advanced stages. In the Kaplan-Meier analysis, lower levels of miRNA-200c
      expression were associated with inferior survival. CONCLUSIONS: Expression levels
      of miRNA-200c might be associated with clinicopathological factors and survival
      in endometrioid endometrial cancer.

PMID- 29355889
TI  - Laeverin protein expression in normal and preeclamptic placentas using tissue
      microarray analysis.
AB  - INTRODUCTION: Laeverin is a placenta-specific protein that is normally expressed
      in the plasma membrane of human trophoblasts. In previous studies, we showed
      higher expression levels of laeverin gene in preeclamptic compared with normal
      placentas and found that laeverin protein was ectopically expressed in the
      cytoplasm of the preeclamptic placentas. Our objective was to investigate
      laeverin protein expression in normal and preeclamptic placentas combining
      immunohistochemistry and immunofluorescence. MATERIAL AND METHODS: Tissue
      microarray analysis of 72 placentas, obtained from 33 preeclamptic and 39
      uncomplicated pregnancies, was performed. Laeverin was labeled with a specific
      antibody for immunohistochemistry and immunofluorescence studies. RESULTS:
      Immunohistochemistry showed that laeverin was expressed in syncytiotrophoblasts,
      cytotrophoblasts and extravillous trophoblasts in all placentas examined. In
      preeclamptic placentas (n = 33) compared with normal placentas (n = 39), laeverin
      was expressed in the cell membrane in 21 (64%) vs. 21 (54%) samples (p = 0.726),
      in the cytoplasm in 3 (9%) vs. 2 (5%) samples (p = 0.795) and in both the
      cytoplasm and membrane in 9 (27%) vs. 16 (41%) samples (p = 0.0522). All
      placental samples that showed cytoplasmic expression of laeverin were obtained
      from women who delivered before 34 weeks of gestation (early-onset preeclampsia).
      Further, immunofluorescence studies showed laeverin expression in the cytoplasm
      of six preeclamptic (three early-onset and three late-onset) and one normal
      placenta but did not reveal any simultaneous cell membrane and cytoplasmic
      expression of laeverin. CONCLUSION: Laeverin is expressed in all trophoblast cell
      types of normal and preeclamptic placentas. Expression pattern of laeverin in
      trophoblast cells is heterogeneous and not necessarily membrane-bound.

PMID- 29355890
TI  - Reducing Off-Label Antipsychotic Use in Older Adults: Time to Look Beyond the
      Doors of Nursing Homes.

PMID- 29355891
TI  - Where Are Antipsychotics Prescribed in Nursing Homes Initiated?
AB  - OBJECTIVES: To describe the settings of care in which antipsychotics that nursing
      home (NH) residents received were likely to have been initiated. DESIGN: Cross
      sectional. SETTING: Iowa NHs. PARTICIPANTS: Fee-for-service Medicare
      beneficiaries who had NH stays between January 1, 2011, and December 31, 2014,
      and had new use of antipsychotics during their NH stays, defined as no
      antipsychotic use in NHs in the last 6 months. MEASUREMENTS: A linked dataset of
      Chronic Condition Data Warehouse Medicare claims and Long-Term Care Minimum Data
      Set (MDS) 3.0 was used to determine care settings of antipsychotic initiations.
      RESULTS: Of 7,496 residents with new antipsychotic use in NHs, 4,794 (64.0%, 95%
      confidence interval (CI) = 62.9-65.0%) initiated them in NHs, 1,392 (18.6%, 95%
      CI 17.7-19.5%) appeared to have had them initiated in hospitals, and 1,310
      (17.5%, 95% CI = 16.6-18.3%) had antipsychotics first dispensed as outpatients.
      Antipsychotics were commonly prescribed during the early NH stays, and 3,026
      (40.4%, 95% CI = 39.3-41.5%) of the entire sample received antipsychotic therapy
      within the first 7 days after NH admissions. Fifty-eight percent (n = 4,348) of
      the study residents initiating antipsychotics had potentially appropriate
      antipsychotic indications according toMDS records. CONCLUSION: Most residents
      initiated antipsychotic therapy in NHs, confirming that NH providers are
      appropriate primary target of interventions to reduce antipsychotic initiation in
      their residents. However, many antipsychotics were continued from other settings,
      indicating a need to evaluate the necessity of continued antipsychotic treatment
      after such transitions of care. J Am Geriatr Soc 66:1082-1088: 2018.

PMID- 29355893
TI  - Cranial measures and ancient DNA both show greater similarity of Neandertals to
      recent modern Eurasians than to recent modern sub-Saharan Africans.
AB  - OBJECTIVES: Ancient DNA analysis has shown that present-day humans of Eurasian
      ancestry are more similar to Neandertals than are present-day humans of sub
      Saharan African ancestry, reflecting interbreeding after modern humans first left
      Africa. We use craniometric data to test the hypothesis that the crania of recent
      modern humans show the same pattern. MATERIALS AND METHODS: We computed
      Mahalanobis squared distances between a published Neandertal centroid based on 37
      craniometric traits and each of 2,413 recent modern humans from the Howells
      global data set (N = 373 sub-Saharan Africans, N = 2,040 individuals of Eurasian
      descent). RESULTS: The average distance to the Neandertal centroid is
      significantly lower for Eurasian crania than for sub-Saharan African crania as
      expected from the findings of ancient DNA (p < 0.001). This result holds when
      examining distances for separate geographic regions of humans of Eurasian descent
      (Europeans, Asians, Australasians, Native Americans, and Pacific Islanders). Most
      of these results are also seen when examining distances partitioning size and
      shape variation. DISCUSSION: Our results show that the genetic difference in
      Neandertal ancestry seen in the DNA of present-day sub-Saharan Africans and
      Eurasians is also found in patterns of recent modern human craniometric
      variation.

PMID- 29355892
TI  - The effect of ethnicity on the performance of protein-creatinine ratio in the
      prediction of significant proteinuria in pregnancies at risk of or with
      established hypertension: an implementation audit and cost implications.
AB  - INTRODUCTION: The replacement of 24-h urine collection by protein-creatinine
      ratio (PCR) for the diagnosis of preeclampsia has been recently recommended.
      However, the literature is conflicting and there are concerns about the impact of
      demographic characteristics on the performance of PCR. MATERIAL AND METHODS: This
      was an implementation audit of the introduction of PCR in a London Tertiary
      obstetric unit. The performance of PCR in the prediction of proteinuria >=300
      mg/day was assessed in 476 women with suspected preeclampsia who completed a 24-h
      urine collection and an untimed urine sample for PCR calculation. Multivariate
      logistic regression was used to assess the independent predictors of significant
      proteinuria. RESULTS: In a pregnant population, ethnicity and PCR are the main
      predictors of >=300 mg proteinuria in a 24-h urine collection. A PCR cut-off of
      30 mg/mmol would have incorrectly classified as non-proteinuric, 41.4% and 22.9%
      of black and non-black women, respectively. Sensitivity of 100% is achieved at
      cut-offs of 8.67 and 20.56 mg/mmol for black and non-black women, respectively.
      Applying these levels as a screening tool to inform the need to perform a 24-h
      urine collection in 1000 women, would lead to a financial saving of ?2911 in non
      black women and to an additional cost of ?3269 in black women. CONCLUSIONS: Our
      data suggest that a move from screening for proteinuria with a 24-h urine
      collection to screening with urine PCR is not appropriate for black populations.
      However, the move may lead to cost-saving if used in the white population with a
      PCR cut-off of 20.5.

PMID- 29355894
TI  - How should minimally important change scores for the Patient-Oriented Eczema
      Measure be interpreted? A validation using varied methods.
AB  - BACKGROUND: The Patient-Oriented Eczema Measure (POEM), scored 0-28, is the core
      outcome instrument recommended for measuring patient-reported atopic eczema
      symptoms in clinical trials. To date, two published studies have broadly
      concurred that the minimally important change (MIC) of the POEM is three points.
      Further assessment of the MIC of POEM in different populations, and using a
      variety of methods, will improve interpretability of the POEM in research and
      clinical practice. OBJECTIVES: To calculate the smallest detectable change in the
      POEM and estimate the MIC of the POEM using a variety of methods in a trial
      dataset of children with moderate-to-severe atopic eczema. METHODS: This study
      used distribution-based and anchor-based methods to calculate the MIC of the POEM
      in children with moderate-to-severe eczema. RESULTS: Data were collected from 300
      children. The smallest detectable change was 2.13. The MIC estimates were 1.07
      (using 0.2 SD of baseline POEM scores) and 2.68 (using 0.5 SD of baseline POEM
      scores) based on distribution-based methods; were 3.09-6.13 based on patient
      /parent-reported anchor-based methods; and were 3.23-5.38 based on investigator
      reported anchor-based methods. CONCLUSIONS: We recommend the following thresholds
      be used to interpret changes in POEM scores: <= 2, unlikely to be a change beyond
      measurement error; 2.1-2.9, a small change detected that is likely to be beyond
      measurement error but may not be clinically important; 3-3.9, probably a
      clinically important change; >= 4, very likely to be a clinically important
      change.

PMID- 29355895
TI  - Is ultrasound measured fetal biometry predictive of intrapartum caesarean section
      for failure to progress?
AB  - BACKGROUND: There are global concerns regarding excessive caesarean rates, which
      could be reduced by identification of risk factors leading to preventative
      measures such as induction of labour. AIMS: This study aims to describe the
      association between antenatal ultrasound and emergency caesarean section for: (i)
      failure to progress; (ii) other indications; and (iii) any indication. MATERIALS
      AND METHODS: Women who had an ultrasound in pregnancy between 36(+0/7) to
      38(+6/7) weeks at Royal Prince Alfred Hospital from January 2005 to June 2009
      were included. Ultrasound parameters were linked to clinical parameters from the
      maternity database. Missing clinical data were imputed and multiple logistic
      regression performed. RESULTS: Fetal biometry data were available for 2006
      pregnancies. After adjusting for maternal age, height, body mass index, parity,
      previous caesarean section and diabetes, caesarean section for failure to
      progress was associated with estimated fetal weight (odds ratio (OR) 2.24 (95%
      CI: 1.76-2.84) per 500 g increase); or biparietal diameter (OR 1.51 (1.16-1.97)
      per 5 mm increase) and abdominal circumference (OR for the 4th quartile (>75th
      centile) compared with the 10-25th centile group was 2.09 (1.13-3.85)).* There
      were also non-linear associations between components of fetal biometry and
      caesarean section for fetal distress and for any indication. CONCLUSIONS:
      Components of fetal biometry in the third trimester are associated with
      intrapartum caesarean section for failure to progress. These parameters could be
      incorporated into models to predict emergency caesarean section which could lead
      to implementation of preventative strategies. *[Corrections added on 29 January
      2018, after first online publication, '(OR for the 4th quartile (>7th centile)'
      has been changed to '(OR for the 4th quartile (>75th centile)'.].

PMID- 29355896
TI  - Differential effects of secukinumab vs. ustekinumab for treatment of psoriasis on
      quality of life, work productivity and activity impairment: a structural equation
      modelling analysis.
AB  - BACKGROUND: The appearance and lifelong, chronic nature of psoriasis result in
      considerable burden to patients, such as sleep impairment, depressive symptoms,
      negative self-esteem and reduced work productivity. OBJECTIVES: To examine direct
      and indirect (mediated) effects of secukinumab vs. ustekinumab on quality of
      life, work productivity and activity impairment based on psoriasis severity and
      symptoms. METHODS: Analyses were based on data from the CLEAR study. Structural
      equation modelling examined the effects of secukinumab vs. ustekinumab on the
      Dermatology Life Quality Index (DLQI) and on the Work Productivity and Activity
      Impairment (WPAI) questionnaire using Psoriasis Area and Severity Index (PASI)
      severity and symptoms (pain, itching and scaling) as potential mediators.
      Analyses were conducted primarily for patients achieving a PASI 90 response (90%
      or greater reduction in PASI from baseline) at week 16 (repeated at week 52) and
      for PASI 50, 75 and 100. RESULTS: Results at weeks 16 and 52 showed that the
      effect of treatment on change in DLQI score was mediated by the PASI 90 response
      and by improvements in itching, pain, and scaling. Achieving any PASI response as
      early as week 16 directly resulted in significantly better WPAI scores. At week
      52, both PASI response and improvement in scaling directly resulted in
      significantly better WPAI scores. Pain, itching and scaling were correlated (r =
      0.51-0.68); improvement in any of these had a significant effect (directly or
      indirectly) on WPAI. All results favoured secukinumab over ustekinumab.
      CONCLUSIONS: The results underscore the important role of both PASI response and
      reduction in symptoms on improvements in health-related quality of life and work
      and daily activity in favour of secukinumab vs. ustekinumab.

PMID- 29355897
TI  - The need for further surgical intervention following primary hysteroscopic
      morcellation of submucosal leiomyomas in women with abnormal uterine bleeding.
AB  - BACKGROUND: Intrauterine hysteroscopic morcellators have been studied as an
      alternative method for removing submucosal leiomyomas. AIMS: To assess the long
      term efficacy of hysteroscopic morcellation of submucosal leiomyomas in women
      with abnormal uterine bleeding (AUB). MATERIALS AND METHODS: We conducted a
      prospective cohort study including all women with AUB who underwent a
      hysteroscopic resection with mechanical morcellation of a benign submucosal
      leiomyoma confirmed at histopathology. Need for further surgery, patient
      satisfaction, symptom resolution and post-operative complications were documented
      by direct patient contact after a minimum of six months of follow-up. RESULTS: A
      total of 73 women were included in the study with a mean length of follow-up of
      32 +/- 13 months. Mean total size of pathology at the time of index surgery was
      of 42 +/- 20 mm. A total of 9/73 (12%) women required subsequent hysterectomy and
      20/73 (27%) any subsequent related surgery (operative hysteroscopy, abdominal
      myomectomy or hysterectomy) with the estimated three-year cumulative incidence
      being 30 +/- 6%. Satisfaction rate of participants was 84%. In multivariate Cox
      proportional analyses, only a total size of pathology of 50 mm or more was found
      to be significantly associated with the risk of requiring further surgical
      procedures (hazard ratio = 2.9, P = 0.02). CONCLUSIONS: Hysteroscopic
      morcellation of submucosal leiomyomas is an effective method to manage women with
      AUB, although women with larger pathology have an increased risk of requiring
      subsequent surgical procedures.

PMID- 29355898
TI  - In vivo dermoscopic and confocal microscopy multistep algorithm to detect in situ
      melanomas.
AB  - BACKGROUND: Although several dermoscopic features of in situ melanoma have been
      identified, data on confocal features of in situ melanoma are still lacking.
      OBJECTIVES: To identify reflectance confocal microscopy (RCM) features of in situ
      melanoma and to develop a diagnostic score combining dermoscopy and RCM. METHODS:
      In total, 120 in situ melanoma and 213 nevi (test set) were retrospectively
      analysed to assess the presence of dermoscopic and RCM criteria. Facial and acral
      lesions were excluded. Spearman's correlation, univariate and multivariate
      regression models were used to identify features significantly correlated with in
      situ melanoma diagnosis. Multivariate results on the test set allowed the
      development of a multistep algorithm, that was tested on a validation set of 100
      lesions. RESULTS: The dermoscopic findings of an atypical network and regression
      were independent predicting factors for in situ melanoma diagnosis [odds ratio
      (OR) 3.44, 95% CI (confidence interval) 1.70-6.97 and OR 4.17, 95% CI 1.93-9.00,
      respectively]. Significant confocal predictors for malignancy were epidermal
      pagetoid spread (OR 2.83, 95% CI 1.32-6.04) and junctional cytological atypia (OR
      3.39, 95% CI 1.38-8.30 if focal, OR 8.44, 95% CI 3.21-22.16 if widespread). A
      multistep diagnostic algorithm able to predict in situ melanoma with a
      sensitivity of 92.5% and a specificity of 61% was developed. The validation set
      confirmed the high diagnostic value (sensitivity 92%, specificity 58%).
      CONCLUSIONS: An easy and reproducible multistep algorithm for in situ melanoma
      detection is suggested, that can be routinely used in tertiary centres.

PMID- 29355899
TI  - Care of pregnant women with decreased fetal movements: Update of a clinical
      practice guideline for Australia and New Zealand.
AB  - The National Health and Medical Research Council (NHMRC) Centre of Research
      Excellence in Stillbirth and the Perinatal Society of Australia and New Zealand
      (PSANZ) have recently partnered in updating an important clinical practice
      guideline, Care of pregnant women with decreased fetal movements. This guideline
      offers 12 recommendations and a suggested care pathway, with the aim to improve
      the quality of care for women reporting decreased fetal movements through an
      evidence-based approach. Adoption of the guideline by clinicians and maternity
      hospitals could result in earlier identification of higher-risk pregnancies,
      improved perinatal health outcomes for women and their babies, and reduced
      stillbirth rates.

PMID- 29355900
TI  - Let's talk about stress, baby! Infant-feeding practices and stress in the ancient
      Atacama desert, Northern Chile.
AB  - AIMS AND OBJECTIVES: The transition to an agricultural economy is often presumed
      to involve an increase in female fertility related to changes in weaning
      practice. In particular, the availability of staple crops as complementary foods
      is hypothesized to allow earlier weaning in agricultural populations. In this
      study, our primary aim is to explore whether this model fits the agricultural
      transition in the Atacama Desert using incremental isotopic analysis. A secondary
      aim of this study is to identify isotopic patterns relating to weaning, and
      assess how these may be differentiated from those relating to early life stress.
      MATERIALS AND METHODS: We use incremental isotopic analysis of dentine to examine
      changes in delta15 N and delta13 C values from infancy and childhood in sites of
      the Arica region (n = 30). We compare individuals from pre-agricultural and
      agricultural phases to establish isotopic patterns and relate these patterns to
      maternal diet, weaning trajectory and physiological stress. RESULTS: We find that
      there is no evidence for systematic temporal or geographic variation in
      incremental isotopic results. Instead, results from all time periods are highly
      variable, with weaning completed between 1.5 and 3.5 years. Characteristics of
      the incremental profiles indicate that both in utero and postnatal stress were a
      common part of the infant experience in the Atacama. DISCUSSION: In the Atacama
      Desert it appears that the arrival of agricultural crops did not result in
      uniform shifts in weaning behavior. Instead, infant and child diet seems to have
      been dictated by the broad-spectrum diets of the mothers, perhaps as a way of
      mitigating the stresses of the harsh desert environment.

PMID- 29355902
TI  - Maternal breast and body symmetry in pregnancy and offspring condition.
AB  - OBJECTIVES: Fluctuating asymmetry (FA) is hypothesized to reflect the level of an
      individual's developmental instability, and therefore genetic quality. As a
      potential signal of biological condition, female body (including breast) symmetry
      was shown to be perceived as more attractive in mate choice context. If symmetry
      reflects a woman's genetic quality, it is possible that FA, similarly to other
      maternal anthropometric cues of biological condition (e.g., body height or waist
      to-hip ratio), may be also related to her offspring condition. MATERIALS AND
      METHODS: To test this, breast and body asymmetry was measured in 93 pregnant
      women in the 1st, 2nd, and 3rd pregnancy trimester. Child's birth weight, length,
      chest and head circumference, information on the Apgar score, congenital
      malformations, and birth complications was taken from hospital records. The
      relationships between offspring birth characteristics and maternal breast FA and
      body FA were analyzed separately, controlled for a child's sex and maternal
      weight in pregnancy. RESULTS: Breast asymmetry was not a predictor of a child's
      neonatal condition assessed from morphological parameters at birth. Asymmetry of
      maternal non-ornamental body characteristcs, commonly used to assess body FA,
      correlated negatively with a child's weight, head and chest circumference at
      birth. DISCUSSION: A composite asymmetry index of eight body traits, non-sexually
      selected characteristics, seems to be a better predictor of a woman's ability to
      invest in fetus during pregnancy than breast asymmetry, sexual ornamentation that
      is perceived as a signal of a woman's attractiveness and biological condition.

PMID- 29355903
TI  - Becoming Kinder: Prosocial Choice and the Development of Interpersonal Regret.
AB  - Three experiments examined children's ability to feel regret following a failure
      to act prosocially. In Experiment 1, ninety 6- to 7-year-olds and one hundred
      seven 7- to 9-year-olds were given a choice to donate a resource to another
      child. If they failed to donate, they discovered that this meant the other child
      could not win a prize. Children in both age groups then showed evidence of
      experiencing regret, although not in control conditions where they had not made
      the choice themselves or their choice did not negatively affect the other child.
      In Experiment 2, eighty-five 5- to 6-year-olds and one hundred nine 7- to 9-year
      olds completed the same task; only the older group showed evidence of regret. In
      Experiment 3, with one hundred thirty-four 6- to 7-year-olds, experiencing regret
      was associated with subsequently making other prosocial choices.

PMID- 29355901
TI  - Depressive symptoms predict head and neck cancer survival: Examining plausible
      behavioral and biological pathways.
AB  - BACKGROUND: Head and neck cancers are associated with high rates of depression,
      which may increase the risk for poorer immediate and long-term outcomes. Here it
      was hypothesized that greater depressive symptoms would predict earlier
      mortality, and behavioral (treatment interruption) and biological (treatment
      response) mediators were examined. METHODS: Patients (n = 134) reported
      depressive symptomatology at treatment planning. Clinical data were reviewed at
      the 2-year follow-up. RESULTS: Greater depressive symptoms were associated with
      significantly shorter survival (hazard ratio, 0.868; 95% confidence interval
      [CI], 0.819-0.921; P < .001), higher rates of chemoradiation interruption (odds
      ratio, 0.865; 95% CI, 0.774-0.966; P = .010), and poorer treatment response (odds
      ratio, 0.879; 95% CI, 0.803-0.963; P = .005). The poorer treatment response
      partially explained the depression-survival relation. Other known prognostic
      indicators did not challenge these results. CONCLUSIONS: Depressive symptoms at
      the time of treatment planning predict overall 2-year mortality. Effects are
      partly influenced by the treatment response. Depression screening and
      intervention may be beneficial. Future studies should examine parallel biological
      pathways linking depression to cancer survival, including endocrine disruption
      and inflammation. Cancer 2018;124:1053-60. (c) 2018 American Cancer Society.

PMID- 29355904
TI  - A multicentre, open, investigator-initiated phase IV clinical trial to evaluate
      the efficacy and safety of ingenol mebutate gel, 0.015% on the face and scalp,
      and 0.05% on the trunk and extremities, in Korean patients with actinic keratosis
      (PERFECT).
AB  - BACKGROUND: Ingenol mebutate gel is a novel, field-directed topical treatment for
      actinic keratosis (AK). Most pivotal studies have targeted Western populations.
      No clinical study has been conducted to investigate its efficacy and safety in
      Asian populations. OBJECTIVES: To evaluate the efficacy and safety of ingenol
      mebutate gel for treating AK of face/scalp and trunk/extremities in a large Asian
      (Korean) population. PATIENTS AND METHODS: In this multicentre, open-label,
      interventional, parallel-group, prospective phase IV study (PERFECT, trial
      registration no.: NCT02716714), the eligible patients were allocated into either
      the face/scalp or the trunk/extremities group, according to their selected
      treatment area location. After application of ingenol mebutate gel, the
      participants were followed up for 6 months. The primary efficacy endpoint was
      complete clearance (CC) of AK lesions in the selected treatment area at day 57.
      Quality of life was evaluated using Skindex-29. Safety endpoints included local
      skin responses, scar, pigmentation, pain and adverse events. RESULTS: In total,
      78.1% [95% confidence interval (CI) 66.86-86.92%] of subjects had CC at day 57,
      with 76.6% (95% CI 64.31-86.25%) in the face/scalp group and 88.9% (95% CI 51.75
      99.72%) in the trunk/extremities group. Among them, CC was sustained in 88.9% (48
      of 54, 95% CI 77.37-95.81%) at month 6. The local skin responses significantly
      increased 1 day after the treatment compared with baseline, and decreased
      afterwards. Among the total subjects, 7.8% (6 of 77) had hyperpigmentation on the
      application area. Scars were not reported. CONCLUSIONS: Ingenol mebutate is
      effective for the treatment of AK in Asians, with tolerable safety profiles.

PMID- 29355905
TI  - Hidradenitis suppurativa, a review of pathogenesis, associations and management.
      Part 1.
AB  - Hidradenitis suppurativa is a chronic, painful, autoinflammatory condition
      resulting in nodules, abscesses and sinus tracts. We present an evidence-based
      review providing new understanding of the pathogenesis of hidradenitis
      suppurativa and associated comorbidities. By the nature of their speciality,
      dermatologists are uniquely positioned to investigate and treat patients with
      this condition. Data collected from a subspecialty hidradenitis suppurativa
      clinic (N = 106) and experiences thereof are discussed in this review.

PMID- 29355906
TI  - Antibiotic therapy for preventing infections in people with acute stroke.
AB  - BACKGROUND: Stroke is the main cause of disability in high-income countries and
      ranks second as a cause of death worldwide. Infections occur frequently after
      stroke and may adversely affect outcome. Preventive antibiotic therapy in the
      acute phase of stroke may reduce the incidence of infections and improve outcome.
      In the previous version of this Cochrane Review, published in 2012, we found that
      antibiotics did reduce the risk of infection but did not reduce the number of
      dependent or deceased patients. However, included studies were small and
      heterogeneous. In 2015, two large clinical trials were published, warranting an
      update of this Review. OBJECTIVES: To assess the effectiveness and safety of
      preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We
      wished to determine whether preventive antibiotic therapy in people with acute
      stroke:* reduces the risk of a poor functional outcome (dependency and/or death)
      at follow-up;* reduces the occurrence of infections in the acute phase of
      stroke;* reduces the occurrence of elevated body temperature (temperature >= 38
      degrees  C) in the acute phase of stroke;* reduces length of hospital stay; or*
      leads to an increased rate of serious adverse events, such as anaphylactic shock,
      skin rash, or colonisation with antibiotic-resistant micro-organisms. SEARCH
      METHODS: We searched the Cochrane Stroke Group Trials Register (25 June 2017);
      the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25
      June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and
      Embase Ovid (1980 to 11 May 2017). In an effort to identify further published,
      unpublished, and ongoing trials, we searched trials and research registers,
      scanned reference lists, and contacted trial authors, colleagues, and researchers
      in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of
      preventive antibiotic therapy versus control (placebo or open control) in people
      with acute ischaemic or haemorrhagic stroke. DATA COLLECTION AND ANALYSIS: Two
      review authors independently selected articles and extracted data; we discussed
      and resolved discrepancies at a consensus meeting with a third review author. We
      contacted study authors to obtain missing data when required. An independent
      review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We
      calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity
      amongst included studies, and performed subgroup analyses on study quality. MAIN
      RESULTS: We included eight studies involving 4488 participants. Regarding quality
      of evidence, trials showed differences in study population, study design, type of
      antibiotic, and definition of infection; however, primary outcomes among the
      included studies were consistent. Mortality rate in the preventive antibiotic
      group was not significantly different from that in the control group (373/2208
      (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high
      quality evidence). The number of participants with a poor functional outcome
      (death or dependency) in the preventive antibiotic therapy group was also not
      significantly different from that in the control group (1158/2168 (53%) vs
      1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate-quality evidence).
      However, preventive antibiotic therapy did significantly reduce the incidence of
      'overall' infections in participants with acute stroke from 26% to 19% (408/2161
      (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high-quality evidence).
      This finding was highly significant for urinary tract infections (81/2131 (4%) vs
      204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high-quality evidence), whereas no
      preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR
      0.95, 95% CI 0.80 to 1.13; high-quality evidence). No major side effects of
      preventive antibiotic therapy were reported. Only two studies qualitatively
      assessed the occurrence of elevated body temperature; therefore, these results
      could not be pooled. Only one study reported length of hospital stay. AUTHORS'
      CONCLUSIONS: Preventive antibiotics had no effect on functional outcome or
      mortality, but significantly reduced the risk of 'overall' infections. This
      reduction was driven mainly by prevention of urinary tract infection; no effect
      for pneumonia was found.

PMID- 29355907
TI  - E-learning for health professionals.
AB  - BACKGROUND: The use of e-learning, defined as any educational intervention
      mediated electronically via the Internet, has steadily increased among health
      professionals worldwide. Several studies have attempted to measure the effects of
      e-learning in medical practice, which has often been associated with large
      positive effects when compared to no intervention and with small positive effects
      when compared with traditional learning (without access to e-learning). However,
      results are not conclusive. OBJECTIVES: To assess the effects of e-learning
      programmes versus traditional learning in licensed health professionals for
      improving patient outcomes or health professionals' behaviours, skills and
      knowledge. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other
      databases and three trial registers up to July 2016, without any restrictions
      based on language or status of publication. We examined the reference lists of
      the included studies and other relevant reviews. If necessary, we contacted the
      study authors to collect additional information on studies. SELECTION CRITERIA:
      Randomised trials assessing the effectiveness of e-learning versus traditional
      learning for health professionals. We excluded non-randomised trials and trials
      involving undergraduate health professionals. DATA COLLECTION AND ANALYSIS: Two
      authors independently selected studies, extracted data and assessed risk of bias.
      We graded the certainty of evidence for each outcome using the GRADE approach and
      standardised the outcome effects using relative risks (risk ratio (RR) or odds
      ratio (OR)) or standardised mean difference (SMD) when possible. MAIN RESULTS: We
      included 16 randomised trials involving 5679 licensed health professionals (4759
      mixed health professionals, 587 nurses, 300 doctors and 33 childcare health
      consultants).When compared with traditional learning at 12-month follow-up, low
      certainty evidence suggests that e-learning may make little or no difference for
      the following patient outcomes: the proportion of patients with low-density
      lipoprotein (LDL) cholesterol of less than 100 mg/dL (adjusted difference 4.0%,
      95% confidence interval (CI) -0.3 to 7.9, N = 6399 patients, 1 study) and the
      proportion with glycated haemoglobin level of less than 8% (adjusted difference
      4.6%, 95% CI -1.5 to 9.8, 3114 patients, 1 study). At 3- to 12-month follow-up,
      low-certainty evidence indicates that e-learning may make little or no difference
      on the following behaviours in health professionals: screening for dyslipidaemia
      (OR 0.90, 95% CI 0.77 to 1.06, 6027 patients, 2 studies) and treatment for
      dyslipidaemia (OR 1.15, 95% CI 0.89 to 1.48, 5491 patients, 2 studies). It is
      uncertain whether e-learning improves or reduces health professionals' skills
      (2912 health professionals; 6 studies; very low-certainty evidence), and it may
      make little or no difference in health professionals' knowledge (3236
      participants; 11 studies; low-certainty evidence).Due to the paucity of studies
      and data, we were unable to explore differences in effects across different
      subgroups. Owing to poor reporting, we were unable to collect sufficient
      information to complete a meaningful 'Risk of bias' assessment for most of the
      quality criteria. We evaluated the risk of bias as unclear for most studies, but
      we classified the largest trial as being at low risk of bias. Missing data
      represented a potential source of bias in several studies. AUTHORS' CONCLUSIONS:
      When compared to traditional learning, e-learning may make little or no
      difference in patient outcomes or health professionals' behaviours, skills or
      knowledge. Even if e-learning could be more successful than traditional learning
      in particular medical education settings, general claims of it as inherently more
      effective than traditional learning may be misleading.

PMID- 29355908
TI  - Losigamone add-on therapy for focal epilepsy.
AB  - BACKGROUND: Epilepsy is a common neurologic disorder, affecting approximately 50
      million people worldwide; nearly a third of these people have epilepsy that is
      not well controlled by a single antiepileptic drug (AED) and they usually require
      treatment with a combination of two or more AEDs. In recent years, many newer
      AEDs have been investigated as add-on therapy for focal epilepsy; losigamone is
      one of these drugs and is the focus of this systematic review. This is an update
      of a Cochrane review first published in 2012 (Cochrane Database of Systematic
      Reviews 2012, Issue 6) and updated in 2015. OBJECTIVES: To investigate the
      efficacy and safety of losigamone when used as an add-on therapy for focal
      epilepsy. SEARCH METHODS: For the latest update on 9 February 2017, we searched
      the Cochrane Epilepsy Specialized Register, CENTRAL and MEDLINE . We searched
      trials registers and contacted the manufacturer of losigamone and authors of
      included studies for additional information. We did not impose any language
      restrictions. SELECTION CRITERIA: Randomized controlled, add-on trials comparing
      losigamone with placebo for focal epilepsy. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed trial quality and extracted data. The
      primary outcomes were 50% or greater reduction in seizure frequency and seizure
      freedom; the secondary outcomes were treatment withdrawal and adverse events.
      Results are presented as risk ratios (RRs) with 95% confidence intervals (CIs) or
      99% CIs (for the individual listed adverse events to make an allowance for
      multiple testing). MAIN RESULTS: Two trials involving a total of 467
      participants, aged over 18 years, were eligible for inclusion. Both trials
      assessed losigamone 1200 mg/day or 1500 mg/day as an add-on therapy for focal
      epilepsy. We assessed one trial as being of good methodological quality while the
      other was of uncertain quality. For the efficacy outcomes, results did show that
      participants taking losigamone were significantly more likely to achieve a 50% or
      greater reduction in seizure frequency (RR 1.76, 95% CI 1.14 to 2.72), but
      associated with a significant increase of treatment withdrawal when compared with
      those taking placebo (RR 2.16, 95% CI 1.28 to 3.67). For the safety outcomes,
      results indicated that the proportion of participants who experienced adverse
      events in the losigamone group was higher than in the placebo group (RR 1.34, 95%
      CI 1.00 to 1.80), dizziness was the only adverse event significantly reported in
      relation to losigamone (RR 3.82, 99% CI 1.69 to 8.64). The proportion of
      participants achieving seizure freedom was not reported in either trial report. A
      subgroup analysis according to different doses of losigamone showed that a higher
      dose of losigamone (1500 mg/day) was associated with a greater reduction in
      seizure frequency than lower doses, but was also associated with more dropouts
      due to adverse events. AUTHORS' CONCLUSIONS: The results of this review showed
      that losigamone did reduce seizure frequency but was associated with more
      treatment withdrawals when used as an add-on therapy for people with focal
      epilepsy. However, the included trials were of short-term duration and uncertain
      quality. Future well-designed randomized, double-blind, placebo-controlled trials
      with a longer-term duration are needed. No new studies have been found since the
      last version of this review. We judged the overall quality of the evidence for
      the outcomes assessed as moderate.

PMID- 29355910
TI  - Courses and Conferences.

PMID- 29355909
TI  - Risperidone versus other antipsychotics for people with severe mental illness and
      co-occurring substance misuse.
AB  - BACKGROUND: Up to 75% of people with serious mental illness (SMI) such as
      schizophrenia and bipolar disorder have co-occurring substance use disorders
      (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and
      prognosis of SMI. OBJECTIVES: To evaluate the effects of risperidone compared to
      treatment with other antipsychotics (first-generation and other second-generation
      antipsychotics) used in people with serious mental illness and co-occurring
      substance misuse. SEARCH METHODS: On 6 January 2016 and 9 October 2017, we
      searched the Cochrane Schizophrenia Group's Study-Based Register of Trials
      (including trial registers). SELECTION CRITERIA: We selected randomised trials of
      risperidone versus any other antipsychotic in people with SMI and substance abuse
      (dual diagnosis). We included trials meeting our inclusion criteria and reporting
      useable data. We excluded trials that either did not meet our inclusion criteria
      or met our inclusion criteria but did not report any useable data. DATA
      COLLECTION AND ANALYSIS: We independently inspected citations and selected
      studies. For included studies, we independently extracted data and appraised
      study quality. For binary outcomes we calculated the risk ratios (RRs) and their
      95% confidence intervals. For continuous outcomes we calculated the mean
      differences (MDs) and their 95% confidence intervals. We pooled data using random
      effects meta-analyses and assessed the quality of evidence, creating a 'Summary
      of findings' table using the GRADE approach. MAIN RESULTS: We identified eight
      randomised trials containing a total of 1073 participants with SMI and co
      occurring substance misuse. Seven of these contributed useable data to the
      review. There was heterogeneity in trial design and measurement. Risperidone was
      compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few
      trials compared risperidone with first-generation agents. Few trials examined
      participants with a dual diagnosis from the outset and most trials only contained
      separate analyses of subgroups with a dual diagnosis or were secondary data
      analyses of subgroups of people with a dual diagnosis from existing larger
      trials.For risperidone versus clozapine we found no clear differences between
      these two antipsychotics in the reduction of positive psychotic symptoms (1
      randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI 
      2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n
      = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence),
      improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to
      2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n =
      36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal
      side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I2 = 0%, very low
      quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI
      0.10 to 2.51; I2 = 34%, very low quality evidence). Clozapine was associated with
      lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to
      11.63, very low quality evidence).For risperidone versus olanzapine we found no
      clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37,
      MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis
      use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence),
      craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low
      quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05,
      very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68,
      95% CI 0.34 to 1.35; I2 = 0%, very low quality evidence).For risperidone versus
      perphenazine, we found no clear differences in the number of participants leaving
      the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality
      evidence).For risperidone versus quetiapine, we found no clear differences in the
      number of participants leaving the study early (1 RCT, n = 294, RR 0.96, 95% CI
      0.86 to 1.07, low-quality evidence).For risperidone versus ziprasidone, we found
      no clear differences in the number of participants leaving the study early (1
      RCT, n = 240, RR 0.96, 95% CI 0.85 to 1.10, low-quality evidence).For many
      comparisons, important outcomes were missing; and no data were reported in any
      study for metabolic disturbances, global impression of illness severity, quality
      of life or mortality. AUTHORS' CONCLUSIONS: There is not sufficient good-quality
      evidence available to determine the effects of risperidone compared with other
      antipsychotics in people with a dual diagnosis. Few trials compared risperidone
      with first-generation agents, leading to limited applicability to settings where
      access to second-generation agents is limited, such as in low- and middle-income
      countries. Moreover, heterogeneity in trial design and measurement of outcomes
      precluded the use of many trials in our analyses. Future trials in this area need
      to be sufficiently powered but also need to conform to consistent methods in
      study population selection, use of measurement scales, definition of outcomes,
      and measures to counter risk of bias. Investigators should adhere to CONSORT
      guidelines in the reporting of results.

PMID- 29355912
TI  - Erratum: Differential investment in body girths by sex: Evidence from 3D photonic
      scanning in a Thai cohort; 163: 696-706. Meghan K. Shirley, Tim J. Cole, Supiya
      Charoensiriwath, Philip Treleaven and Jonathan C.K. Wells. DOI:
      10.1002/ajpa.23238.

PMID- 29355911
TI  - The Brain Health Assessment for Detecting and Diagnosing Neurocognitive
      Disorders.
AB  - BACKGROUND/OBJECTIVES: Brief cognitive screens lack the sensitivity to detect
      mild cognitive impairment (MCI) or support differential diagnoses. The objective
      of this study was to validate the 10-minute, tablet-based University of
      California, San Francisco (UCSF) Brain Health Assessment (BHA) to overcome these
      limitations. DESIGN: Cross-sectional. SETTING: UCSF Memory and Aging Center.
      PARTICIPANTS: Older adults (N = 347) (neurologically healthy controls (n = 185),
      and individuals diagnosed with MCI (n = 99), dementia (n = 42), and as normal
      with concerns (n = 21)). MEASUREMENTS: The BHA includes subtests of memory,
      executive function and speed, visuospatial skills, and language and an optional
      informant survey. Participants completed the Montreal Cognitive Assessment (MoCA)
      and criterion-standard neuropsychological tests. Standardized structural 3T brain
      magnetic resonance imaging was performed in 145 participants. RESULTS: At a fixed
      85% specificity rate, the BHA had 100% sensitivity to dementia and 84% to MCI;
      the MoCA had 75% sensitivity to dementia and 25% to MCI. The BHA had 83%
      sensitivity to MCI likely due to AD and 88% to MCI unlikely due to AD, and the
      MoCA had 58% sensitivity to MCI likely AD and 24% to MCI unlikely AD. The BHA
      subtests demonstrated moderate to high correlations with the criterion-standard
      tests from their respective cognitive domains. Memory test performance correlated
      with medial temporal lobe volumes; executive and speed with frontal, parietal,
      and basal ganglia volumes; and visuospatial with right parietal volumes.
      CONCLUSION: The BHA had excellent combined sensitivity and specificity to detect
      dementia and MCI, including MCI due to diverse etiologies. The subtests provide
      efficient, valid measures of neurocognition that are critical in making a
      differential diagnosis.

PMID- 29355913
TI  - Crisis in healthcare: Time for academic clinicians to assume leadership roles.

PMID- 29355914
TI  - Intraoperative imaging technology to maximise extent of resection for glioma.
AB  - BACKGROUND: Extent of resection is considered to be a prognostic factor in neuro
      oncology. Intraoperative imaging technologies are designed to help achieve this
      goal. It is not clear whether any of these sometimes very expensive tools (or
      their combination) should be recommended as standard care for people with brain
      tumours. We set out to determine if intraoperative imaging technology offers any
      advantage in terms of extent of resection over standard surgery and if any one
      technology was more effective than another. OBJECTIVES: To establish the overall
      effectiveness and safety of intraoperative imaging technology in resection of
      glioma. To supplement this review of effects, we also wished to identify cost
      analyses and economic evaluations as part of a Brief Economic Commentary (BEC).
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (Issue 7, 2017), MEDLINE (1946 to June, week 4, 2017), and Embase (1980
      to 2017, week 27). We searched the reference lists of all identified studies. We
      handsearched two journals, the Journal of Neuro-Oncology and Neuro-oncology, from
      1991 to 2017, including all conference abstracts. We contacted neuro-oncologists,
      trial authors, and manufacturers regarding ongoing and unpublished trials.
      SELECTION CRITERIA: Randomised controlled trials evaluating people of all ages
      with presumed new or recurrent glial tumours (of any location or histology) from
      clinical examination and imaging (computed tomography (CT) or magnetic resonance
      imaging (MRI), or both). Additional imaging modalities (e.g. positron emission
      tomography, magnetic resonance spectroscopy) were not mandatory. Interventions
      included intraoperative MRI (iMRI), fluorescence-guided surgery, ultrasound, and
      neuronavigation (with or without additional image processing, e.g. tractography).
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the
      search results for relevance, undertook critical appraisal according to known
      guidelines, and extracted data using a prespecified pro forma. MAIN RESULTS: We
      identified four randomised controlled trials, using different intraoperative
      imaging technologies: iMRI (2 trials including 58 and 14 participants,
      respectively); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1
      trial, 322 participants); and neuronavigation (1 trial, 45 participants). We
      identified one ongoing trial assessing iMRI with a planned sample size of 304
      participants for which results are expected to be published around autumn 2018.
      We identified no trials for ultrasound.Meta-analysis was not appropriate due to
      differences in the tumours included (eloquent versus non-eloquent locations) and
      variations in the image guidance tools used in the control arms (usually
      selective utilisation of neuronavigation). There were significant concerns
      regarding risk of bias in all the included studies. All studies included people
      with high-grade glioma only.Extent of resection was increased in one trial of
      iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI)
      0.02 to 0.96; 1 study, 49 participants; very low-quality evidence) and in the
      trial of 5-ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study,
      270 participants; low-quality evidence). The other trial assessing iMRI was
      stopped early after an unplanned interim analysis including 14 participants,
      therefore the trial provides very low-quality evidence. The trial of
      neuronavigation provided insufficient data to evaluate the effects on extent of
      resection.Reporting of adverse events was incomplete and suggestive of
      significant reporting bias (very low-quality evidence). Overall, reported events
      were low in most trials. There was no clear evidence of improvement in overall
      survival with 5-ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270
      participants; low-quality evidence). Progression-free survival data were not
      available in an appropriate format for analysis. Data for quality of life were
      only available for one study and suffered from significant attrition bias (very
      low-quality evidence). AUTHORS' CONCLUSIONS: Intra-operative imaging
      technologies, specifically iMRI and 5-ALA, may be of benefit in maximising extent
      of resection in participants with high grade glioma. However, this is based on
      low to very low quality evidence, and is therefore very uncertain. The short- and
      long-term neurological effects are uncertain. Effects of image-guided surgery on
      overall survival, progression-free survival, and quality of life are unclear. A
      brief economic commentary found limited economic evidence for the equivocal use
      of iMRI compared with conventional surgery. In terms of costs, a non-systematic
      review of economic studies suggested that compared with standard surgery use of
      image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic
      acid was more costly. Further research, including studies of ultrasound-guided
      surgery, is needed.

PMID- 29355915
TI  - How to assess goals in intrathecal baclofen therapy.

PMID- 29355916
TI  - Ghosts of mother's past: Previous maternal stress leads to altered maternal
      behavior following a subsequent pregnancy in rats.
AB  - A rodent model was used to explore whether mothers that experienced a postnatal
      stressor in the past (i.e., daily separations from her previous litter) exhibited
      altered maternal behavior during a typical, subsequent rearing experience. Stress
      naive female rats were bred and then separated from their pups (maternal
      separation) or remained with their pups (standard-rearing). After those pups were
      weaned, mothers were bred again with all pups from the subsequent litter being
      standard-reared. In the first week of life, various maternal behaviors directed
      towards these subsequent offspring were observed, including levels of nursing and
      pup retrieval. After weaning, mothers were tested for anxiety-like behavior, as
      well as memory on the object-recognition and object-placement tasks. The results
      show that previously stressed mothers retrieve their offspring significantly
      faster compared to mothers with no stress history, which may reflect a more
      "overprotective" mothering style. No other differences on maternal care were
      observed. Also, while previously stressed mothers were no more anxious than
      control mothers, they had impaired spatial memory on the object-placement task.
      This was not due to a general memory impairment as mothers performed equally on
      the object-recognition task, suggesting that previous maternal stress has
      specific effects on hippocampal-dependent tasks. That is, stress exerts lasting
      effects on types of behavior that are proposed to be beneficial to mothers and
      their offspring (i.e., efficient foraging and navigation abilities). Taken
      together, these results provide evidence that stress has specific and persistent
      effects on caregivers.

PMID- 29355917
TI  - Radiotherapy regimens in patients with nonmelanoma head and neck skin cancers.
AB  - BACKGROUND: To assess the effectiveness and outcomes of adjuvant radiotherapy
      regimens for nonmelanoma skin cancers (NMSC) of the head and neck, particularly
      for elderly patients. METHODS: A retrospective review of patients with head and
      neck NMSC was conducted. Radiotherapy dose per fraction regimens included <=200,
      240-250, 300-400, and 500-600 cGy. Demographics, tumor characteristics, local
      control (LC), regional control (RC), and survival outcomes were analyzed.
      RESULTS: Of the 90 patients with 140 disease sites, 76.6% were squamous cell
      carcinoma, 15.5% were basal cell carcinoma, and 7.7% were other histologies. The
      mean age at diagnosis was 72.1 years old. The most common location was
      preauricular (20.0%), followed by temple, scalp, cheek, and forehead. The overall
      LC and RC rates were 88.8% and 88.8%, respectively by patients, and 92.8% and
      86.4%, respectively by treatment sites. Age, primary tumor location, T
      classification, N classification, overall stage, perineural invasion, comorbid
      disease, skull base invasion, and radiotherapy subgroup were significantly
      associated with disease-free and overall survival (P < 0.05). LC and RC were not
      significantly different among the radiotherapy dose subgroups. The mean survival
      was longer in patients treated with 240-250 cGy/fraction (50.3 months). There was
      no significant difference in radiotherapy toxicity between the subgroups.
      CONCLUSION: Short-term radiotherapy regimens for patients with locally or
      regionally advanced head and neck NMSC appear feasible and effective,
      particularly in elderly patients or those that cannot tolerate the length of
      standard regimens.

PMID- 29355918
TI  - Oxytocin receptor gene polymorphisms (rs53576) and early paternal care sensitize
      males to distressing female vocalizations.
AB  - The oxytocinergic system is highly involved in social bonding and early caregiver
      infant interactions. Here, we hypothesize that oxytocin receptor (OXTR) gene
      genotype and parental bonding history interact in influencing social development.
      To address this question, we assessed adult males' arousal (heart rate changes)
      in response to different distress vocalizations (human female, human infant and
      bonobo). Region rs53576 of the OXTR gene was genotyped from buccal mucosa cell
      samples, and a self-report Parental Bonding Instrument was used (which provide
      information about parental care or parental overprotection). A significant gene
      environment interaction between OXTR genotype and parenting style was found to
      influence participants' social responsivity to female cry vocalizations.
      Specifically, a history of appropriate paternal care in participants accentuated
      the heightened social sensitivity determined by G/G homozygosity, while higher
      versus lower paternal overprotection lead to distinct levels of physiological
      arousal particularly in A carriers individuals. These results add to our
      understanding of the dynamic interplay between genetic susceptibility and early
      environmental experience in shaping the development of appropriate social
      sensitivity in males.

PMID- 29355920
TI  - Testing the Impact of Mixed-Mode Designs (Mail and Web) and Multiple Contact
      Attempts within Mode (Mail or Web) on Clinician Survey Response.
AB  - OBJECTIVE: To compare response rate and nonresponse bias across two mixed-mode
      survey designs and two single-mode designs. DATA SOURCES: This experiment was
      embedded in a clinician survey of knowledge and attitudes regarding HPV
      vaccination (n = 275). STUDY DESIGN: Clinicians were randomly assigned one of two
      mixed-mode (mail/web or web/mail) or single-mode designs (mail-only/web-only).
      Differences in response rate and nonresponse bias were assessed. PRINCIPAL
      FINDINGS: Using a multiple-contact protocol increased response, and sending a web
      survey first provided the more rapid response. Overall, the mixed-mode survey
      designs generated final response rates approximately 10 percentage points higher
      than their single-mode counterparts, although only the final response differences
      between the mail-only and web/mail conditions attained statistical significance
      (32.1 percent vs. 48 percent, respectively; p = .005). Observed differences did
      not result in nonresponse bias. CONCLUSIONS: Results support mixing modes of
      survey administration and web-based data collection in a multiple contact survey
      data collection protocol.

PMID- 29355922
TI  - A new class of genic nuclear RNA species in Arabidopsis.
AB  - Targeting of ArabidopsisPHABULOSA (PHB) mRNA by miR166 has been implicated in
      gene body methylation at the PHB locus. We report that the PHB locus produces an
      array of stable nuclear RNA species that are neither polyadenylated nor capped.
      Their biogenesis requires neither RNA polymerases IV/V nor miR166-guided
      cleavage. The PHB RNAs are insensitive to mutation of nuclear RNA decay pathways
      and are conserved in several Brassicaceae species, suggesting functional
      relevance. Similar RNA species are also produced by another body-methylated locus
      encoding the miR414 target eIF2. Our data reveal the existence of a new class of
      genic nuclear RNA species.

PMID- 29355921
TI  - Newborns are sensitive to the correspondence between auditory pitch and
      visuospatial elevation.
AB  - Amodal (redundant) and arbitrary cross-sensory feature associations involve the
      context-insensitive mapping of absolute feature values across sensory domains.
      Cross-sensory associations of a different kind, known as correspondences, involve
      the context-sensitive mapping of relative feature values. Are such
      correspondences in place at birth (like amodal associations), or are they learned
      from subsequently experiencing relevant feature co-occurrences in the world (like
      arbitrary associations)? To decide between these two possibilities, human
      newborns (median age = 44 hr) watched animations in which two balls alternately
      rose and fell together in space. The pitch of an accompanying sound rose and fell
      either congruently with this visual change (pitch rising and falling as the balls
      moved up and down), or incongruently (pitch rising and falling as the balls moved
      down and up). Newborns' looking behavior was sensitive to this congruence,
      providing the strongest indication to date that cross-sensory correspondences can
      be in place at birth.

PMID- 29355919
TI  - Origins of natural killer cell memory: special creation or adaptive evolution.
AB  - The few initial formative studies describing non-specific and apparently
      spontaneous activity of natural killer (NK) cells have since multiplied into
      thousands of scientific reports defining their unique capacities and means of
      regulation. Characterization of the array of receptors that govern NK cell
      education and activation revealed an unexpected relationship with the major
      histocompatibility molecules that NK cells originally became well known for
      ignoring. Proceeding true to form, NK cells continue to up-end archetypal
      understanding of their ever-expanding capabilities. Discovery that the NK cell
      repertoire is extremely diverse and can be reshaped by particular viruses into
      unique subsets of adaptive NK cells challenges, or at least broadens, the
      definition of immunological memory. This review provides an overview of studies
      identifying adaptive NK cells, addressing the origins of NK cell memory and
      introducing the heretical concept of NK cells with extensive antigenic
      specificity. Whether these newly apparent properties reflect adaptive utilization
      of known NK cell attributes and receptors or a specially creative allocation from
      an undefined receptor array remains to be fully determined.

PMID- 29355923
TI  - Heart rate as a predictor of cardiovascular risk.
AB  - BACKGROUND: Heart rate (HR) is a predictor of cardiovascular, cerebrovascular and
      all-cause mortality in the general population, as well as in patients with cardio
      and cerebrovascular diseases. We aimed to summarize current knowledge regarding
      the influence of HR on cardio- and cerebrovascular morbidity and mortality.
      MATERIALS AND METHODS: PubMed, MEDLINE, Ovid and EMBASE databases were searched
      for large follow-up studies or meta-analysis published between January 1990 and
      September 2017 in the English language using the following keyword "heart rate,"
      "resting heart rate," "mortality," "outcome," "hypertension," "heart failure,"
      "ischaemic heart disease," "coronary heart disease" and "stroke." RESULTS: The
      relationship between increased HR and cardio- and cerebrovascular morbidity and
      mortality has been reported in a large number of studies, and the results
      regarding this association are concurrent. This connection is generally stronger
      in men than in women. The increase in HR usually occurs in parallel with
      elevation of blood pressure and metabolic disturbances (insulin resistance,
      dyslipidaemia). However, even after adjustment for the most important
      cardiovascular risk factors, HR remained an independent predictor of adverse
      events in global population or in patients with cardio- and cerebrovascular
      diseases. CONCLUSION: HR has an important negative effect on cardio- and
      cerebrovascular morbidity and mortality. Future longitudinal investigations
      should clarify HR significance and optimal HR reduction for primary and secondary
      prevention in cardio- and cerebrovascular events.

PMID- 29355924
TI  - Adolescent Perspectives on the Burden of a Parent's Migraine: Results from the
      CaMEO Study.
AB  - OBJECTIVE: To assess the impact of parental migraine on adolescents (aged 13-21
      years) living within the parental home from the adolescent's perspective.
      BACKGROUND: Family members are affected by their parent's migraine. We surveyed
      adolescents on the social, academic, and emotional effects of their parent's
      migraine. METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) study
      was a longitudinal Web-based study with cross-sectional modules designed to
      assess migraine symptoms, severity, frequency, and disability; migraine-related
      consulting practices, healthcare utilization, medication use, comorbid health
      conditions, and family related burden associated with migraine. The Family Burden
      Module (adolescent version; FBM-A) from the CaMEO study assessed parents with
      migraine and adolescent household members (dyads). Adolescents ranged in age from
      13-21 years and were living at home with their parent. The initial FBM-A survey
      included 52 items covering five domains, which was refined and reduced by
      confirmatory factor analysis to 36 items covering four domains. Depression (9
      item Patient Health Questionnaire) and anxiety (7-item Generalized Anxiety
      Disorder scale) were assessed. Item responses were stratified by parent migraine
      status (episodic migraine [EM], <15 headache days/month; chronic migraine [CM],
      >=15 headache days/month). Frequencies of activities/events missed because of
      parental headache were categorized as >=1 time or >=4 times/previous 30 days.
      RESULTS: The sample included 1,411 parent-adolescent dyads (parent with EM, n =
      1,243 [88.1%]; parent with CM, n = 168 [11.9%]). Burden due to a parent's
      migraine was reported in four domains based on 36 items including: Loss of
      Parental Support and Reverse Caregiving (5 items); Emotional Experience (13
      items); Interference with School (4 items); and Missed Activities and Events (14
      items). Across domains, perceived burden was greater for adolescents of parents
      with CM vs EM. Rates of moderate-to-severe anxiety symptoms were higher among
      adolescents of parents with CM (6.2 vs 11.3%, P = .01), while moderate-to-severe
      depression symptom rates were similar (5.5 vs 8.9%, P = .08). More adolescents of
      CM vs EM parents reported having a headache within the previous 3 months (P <
      .001). CONCLUSIONS: Parental migraine negatively impacts adolescent children,
      extending our understanding of the family burden of migraine and emphasizing the
      potential benefit to children of optimizing migraine care.

PMID- 29355925
TI  - Impact of the 340B Drug Pricing Program on Cancer Care Site and Spending in
      Medicare.
AB  - OBJECTIVE: To examine the impact of the 340B drug discount program on the site of
      cancer drug administration and cancer care spending in Medicare. DATA
      SOURCES/STUDY SETTING: 2010-2013 Medicare claims data for a random sample of
      Medicare Fee-for-Service beneficiaries with cancer. STUDY DESIGN: We identified
      the 340B effect using variation in the availability of 340B hospitals across
      markets. We considered beneficiaries from markets that newly gained a 340B
      hospital during the study period (new 340B markets) as the treatment group.
      Beneficiaries in markets with no 340B hospital were the control group. We used a
      difference-in-differences approach with market fixed effects. DATA COLLECTION:
      Secondary data analysis. PRINCIPAL FINDINGS: The probability of a patient
      receiving cancer drug administration in hospital outpatient departments (HOPDs)
      versus physician offices increased 7.8 percentage points more in new 340B markets
      than in markets with no 340B hospital. Per-patient spending on other cancer care
      increased $1,162 more in new 340B markets than in markets with no 340B hospital.
      CONCLUSIONS: The 340B program shifted the site of cancer drug administration to
      HOPDs and increased spending on other cancer care. As the program expands,
      continuing assessment of its impact on service utilization and spending would be
      needed.

PMID- 29355926
TI  - Plant S6 kinases do not require hydrophobic motif phosphorylation for activity in
      yeast lacking Ypk3.
AB  - The ribosomal protein S6 kinases (S6K) are among the major substrates and crucial
      effectors of the target of rapamycin (TOR) kinase, which is an evolutionarily
      conserved regulator of cell growth and proliferation. Recent research indicates
      that yeast Ypk3 is an ortholog of mammalian S6Ks. Here, we find that plant S6Ks
      restore ribosomal protein S6 phosphorylation in a rapamycin-sensitive manner in
      yeast cells lacking Ypk3. However, phosphorylation of a hydrophobic motif, which
      is mediated through TOR signaling and essential for mammalian S6K activity, is
      not detected in plant S6Ks. Furthermore, deletion of the N-terminal region of
      rice S6Ks shows phosphorylation of the hydrophobic motif and reduced rapamycin
      sensitivity. Our findings suggest a mechanism of plant S6K activation distinct
      from that of mammalian S6Ks.

PMID- 29355927
TI  - Early Impact of the Affordable Care Act Coverage Expansion on Safety-Net Hospital
      Inpatient Payer Mix and Market Shares.
AB  - OBJECTIVE: To examine the impact of the Affordable Care Act's coverage expansion
      on safety-net hospitals (SNHs). STUDY SETTING: Nine Medicaid expansion states.
      STUDY DESIGN: Differences-in-differences (DID) models compare payer-specific pre
      post changes in inpatient stays of adults aged 19-64 years at SNHs and non-SNHs.
      DATA COLLECTION METHODS: 2013-2014 Healthcare Cost and Utilization Project State
      Inpatient Databases. PRINCIPAL FINDINGS: On average per quarter postexpansion,
      SNHs and non-SNHs experienced similar relative decreases in uninsured stays (DID
      = -2.2 percent, p = .916). Non-SNHs experienced a greater percentage increase in
      Medicaid stays than did SNHs (DID = 13.8 percent, p = .041). For SNHs, the
      average decrease in uninsured stays (-146) was similar to the increase in
      Medicaid stays (153); privately insured stays were stable. For non-SNHs, the
      decrease in uninsured (-63) plus privately insured (-33) stays was similar to the
      increase in Medicaid stays (105). SNHs and non-SNHs experienced a similar
      absolute increase in Medicaid, uninsured, and privately insured stays combined
      (DID = -16, p = .162). CONCLUSIONS: Postexpansion, non-SNHs experienced a greater
      percentage increase in Medicaid stays than did SNHs, which may reflect patients
      choosing non-SNHs over SNHs or a crowd-out of private insurance. More research is
      needed to understand these trends.

PMID- 29355928
TI  - Physician Market Structure, Patient Outcomes, and Spending: An Examination of
      Medicare Beneficiaries.
AB  - OBJECTIVE: To understand the impact of changes in physician market structure on
      clinical outcomes and health care utilization. DATA SOURCES: 2005-2012 Medicare
      fee-for-service claims and enrollment data. STUDY DESIGN: We consider the effect
      of cardiology market structure on utilization and health outcomes for four
      patient populations. We estimate the risk-adjusted impact of competition using
      multivariate regression models. PRINCIPAL FINDINGS: The study finds that an
      increase in consolidation leads to statistically and economically significant
      increases in negative health outcomes. For example, we find that moving from a
      zip code at the 25th percentile of cardiology market concentration to one at the
      75th percentile would be associated with 5 to 7 percent increases in risk
      adjusted mortality for three of the sample populations. We also found higher
      expenditures in more concentrated markets. For example, moving from a zip code at
      the 25th percentile of cardiology market concentration to one at the 75th would
      be associated with 7 to 11 percent increases in expenditures, depending on sample
      population. CONCLUSIONS: Our estimates indicate that increases in cardiology
      market concentration are associated with worse health outcomes and higher health
      care expenditures. Some effects may be attributed to vertical as well as
      horizontal changes.

PMID- 29355929
TI  - Small fluorescent molecules for monitoring autophagic flux.
AB  - We have developed two types of fluorescent probes, DALGreen and DAPGreen, for
      monitoring autophagy, that exhibit fluorescence upon being incorporated into
      autophagosomes. DALGreen enhances its fluorescence at acidic pH, which is
      favorable for monitoring late-phase autophagy, whereas DAPGreen remains
      fluorescent with almost constant brightness during the autophagic process. With
      these probes that stain autophagosomes as they are being formed, the real-time
      change of autophagic phenomena of live cells may be traced, which is an advantage
      over conventional approaches with small molecules that stain mature
      autophagosomes. The use of both dyes allows monitoring of the membrane dynamics
      of autophagy in any type of cell without the need for genetic engineering, and
      therefore, will be useful as a tool to study autophagic phenomena.

PMID- 29355931
TI  - Sensory improvement of leprosy peripheral neuropathy in patients treated with
      perineural injection of platelet-rich plasma.

PMID- 29355930
TI  - IgG from atopic dermatitis patients induces IL-17 and IL-10 production in infant
      intrathymic TCD4 and TCD8 cells.
AB  - INTRODUCTION: Our group recently demonstrated that IgG modulates alphabetaT cell
      cytokine production during the maturation process in the human thymus. The
      effects of this modulation are IgG repertoire dependent and can exert a systemic
      and long-term impact. OBJECTIVE: To investigate whether IgG from atopic
      dermatitis (AD) patients can modulate cytokine production of infant intrathymic
      TCD4 and TCD8 cells in vitro. METHODS: Thymic tissues were obtained from newborn
      children from nonatopic mothers, and thymocytes were cultured for 6 days with
      purified IgG from AD patients or with intravenous immunoglobulin (IVIG) or mock
      conditions as controls. Cells were gated as double positive T cells (TDP- CD4+
      CD8+ ), TCD4 cells (CD4+ CD8- ), or TCD8 cells (CD4- CD8+ ), and intracellular
      levels of IL-17A, IFN-gamma, TNF-alpha, IL-4, IL-10, and TGF-beta were evaluated
      by flow cytometry. RESULTS: Compared to mock and IVIG culture conditions, IgG of
      AD individuals induced in vitro intracellular production of IL-17 and IL-10 by
      intrathymic TDP, TCD4, and TCD8 cells of infants. TGF-beta was also detected at a
      higher frequency in response to AD IgG in TDP and TCD8 cells compared to mock and
      IVIG cultured conditions. An opposite effect was detected upon IFN-gamma
      production in TCD4 cells, such that AD IgG reduced IFN-gamma production compared
      to production under mock conditions but not under IVIG conditions. CONCLUSION:
      IgG of AD patients can stimulate cytokine production in infant thymocytes and
      thus resembles the peripheral profile observed in adults. These findings suggest
      a novel mechanism that can contribute to AD pathogenesis.

PMID- 29355932
TI  - Dietary consumption of antioxidant vitamins and subsequent lung cancer risk: The
      Japan Public Health Center-based prospective study.
AB  - While many epidemiological studies have studied the association between lung
      cancer risk and fruits and vegetable consumption (the major sources of
      antioxidant vitamins), only a few have investigated the direct association with
      antioxidants in consideration of cancer subtypes and smoking status. Here, we
      examined the association between consumption of antioxidant vitamins and lung
      cancer risk in one of the largest prospective cohort studies in Japan. We
      investigated the association of dietary antioxidant vitamins intake, namely
      retinol, vitamin C, vitamin E, alpha-carotene, and beta-carotene and subsequent
      incidence of lung cancer among 38,207 men and 41,498 women in the Japan Public
      Health Center-based prospective study. Cox proportional hazard regression was
      performed with adjustment for potential confounders and by strata of cancer
      subtypes and smoking status. Antioxidant and other dietary intakes were assessed
      using a food frequency questionnaire (FFQ). During 1,233,096 person-years of
      follow-up between 1995 and 2013, a total of 1,690 lung cancer cases were newly
      diagnosed. In a multivariate regression model, while higher retinol intake was
      positively associated with overall lung cancer risk in men (HR 1.26; 95% CI 1.05
      1.51; ptrend  = 0.003), the estimates were more evident with small cell carcinoma
      (HR 1.92; 95% CI 1.13-3.24; ptrend  < 0.001). Null associations were observed for
      other antioxidant vitamins. Our prospective study suggests that higher
      consumption of retinol may be associated with an increased risk of lung cancer in
      men, especially with small cell carcinoma, although confirmation is required.

PMID- 29355933
TI  - Ablation of hephaestin and ceruloplasmin results in iron accumulation in
      adipocytes and type 2 diabetes.
AB  - Little is known about the iron efflux mechanism in adipocytes. Here, we used
      hephaestin (Heph) and ceruloplasmin (Cp) single-knockout (KO) mice and Heph/Cp
      double-KO mice to investigate the roles of multicopper ferroxidases (MCFs) in
      this process. We show that both HEPH and CP are expressed in subcutaneous adipose
      tissue. Ablation of either MCF leads to a compensatory increase in the other,
      which contributes to the balance of iron status. However, ablation of both MCFs
      together induces severe iron deposition in adipocytes which is associated with
      decreased adiponectin and leptin mRNA expression. Furthermore, Heph/Cp KO mice
      display disordered carbohydrate metabolism characterized as type 2 diabetes.
      Together, these results demonstrate the protective roles of HEPH and CP in
      preventing iron overload in adipocytes.

PMID- 29355935
TI  - Electrical pulse stimulation induces GLUT4 translocation in a Rac-Akt-dependent
      manner in C2C12 myotubes.
AB  - Muscle contraction increases skeletal muscle glucose uptake, but the underlying
      mechanisms are not fully elucidated. While important for insulin-stimulated
      glucose uptake, the role of Akt in contraction-stimulated muscle glucose uptake
      is controversial. In our study, C2C12 skeletal muscle myotubes were contracted by
      electrical pulse stimulation (EPS). We found that EPS leads to Akt
      phosphorylation on sites S473 and T308 in a time-dependent manner. The Akt
      inhibitor MK2206 partly reduces EPS-stimulated GLUT4 translocation without
      affecting EPS-stimulated AMPK phosphorylation. EPS activates Rac1 GTP-binding,
      and EPS-stimulated GLUT4 translocation is partly inhibited by Rac1 inhibitor II
      and siRac1. Interestingly, both Rac1 inhibitor II and siRac1 inhibit EPS
      stimulated Akt phosphorylation on sites S473 and T308. Our findings implicate a
      Rac1-Akt signaling pathway in EPS-stimulated GLUT4 translocation in C2C12
      myotubes.

PMID- 29355934
TI  - Cross-Sector Collaboration in the High-Poverty Setting: Qualitative Results from
      a Community-Based Diabetes Intervention.
AB  - OBJECTIVE: To characterize the motivations of stakeholders from diverse sectors
      who engaged in cross-sector collaboration with an academic medical center. DATA
      SOURCE: Primary qualitative data (2014-2015) were collected from 22 organizations
      involved in a cross-sector diabetes intervention on the South Side of Chicago.
      STUDY DESIGN: In-depth, semistructured interviews; participants included leaders
      from all stakeholder organization types (e.g., businesses, community development,
      faith-based) involved in the intervention. DATA COLLECTION METHODS: Data were
      transcribed verbatim from audio and video recordings. Analysis was conducted
      using the constant comparison method, derived from grounded theory. PRINCIPAL
      FINDINGS: All stakeholders described collaboration as an opportunity to promote
      community health in vulnerable populations. Among diverse motivations across
      organization types, stakeholders described collaboration as an opportunity for:
      financial support, brand enhancement, access to specialized skills or knowledge,
      professional networking, and health care system involvement in community-based
      efforts. Based on our findings, we propose a framework for implementing a working
      knowledge of stakeholder motivations to facilitate effective cross-sector
      collaboration. CONCLUSIONS: We identified several factors that motivated
      collaboration across diverse sectors with health care systems to promote health
      in a high-poverty, urban setting. Understanding these motivations will be
      foundational to optimizing meaningful cross-sector collaboration and improving
      diabetes outcomes in the nation's most vulnerable communities.

PMID- 29355936
TI  - Auditory structural connectivity in preterm and healthy term infants during the
      first postnatal year.
AB  - Assessing language development in the first postnatal year is difficult, as
      receptive and expressive skills are rudimentary. Although outward manifestations
      of change are limited, the auditory language system is thought to undergo
      critical development at this age, as the foundations are laid for the rapid onset
      of spoken language in the second and third years. We recruited 11 infants, 7
      healthy controls (gestational age = 40.69 +/- 0.56; range from 40 to 41.43) and
      preterm babies (gestational age = 28.04 +/- 0.95; range from 27.43 to 29.43) who
      underwent a Magnetic Resonance Imaging study during the first postnatal year (age
      at scan = 194.18 +/- 97.98). We assessed white matter tracts using diffusion
      weighted magnetic resonance imaging with probabilistic tractography. Fractional
      anisotropy was found to be largely mature even at one month, although there was a
      little further increase during the first postnatal year in both the acoustic
      radiation and the direct brainstem-Heschl's pathway.

PMID- 29355937
TI  - Chronic pruritic warty papules on the buttocks.

PMID- 29355938
TI  - A case of paraneoplastic elastosis perforans serpiginosa associated with ovarian
      malignancy.
AB  - Elastosis perforans serpiginosa (EPS) is a rare skin disorder in which there is
      transepithelial elimination of elastin fibers. It belongs to a group of
      perforating disorders of which there are four classic types. The EPS type is
      extremely rare. There have been no previous reports of elastosis perforans
      serpiginosa occurring as a paraneoplastic phenomenon. We report a case of
      paraneoplastic elastosis perforans serpiginosa in the setting of stage 4 ovarian
      cancer.

PMID- 29355939
TI  - Inflammatory potential of diet and risk of pancreatic cancer in the Prostate,
      Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
AB  - Inflammation plays a central role in pancreatic cancer etiology and can be
      modulated by diet. We aimed to examine the association between the inflammatory
      potential of diet, assessed with the Dietary Inflammatory Index (DII(r)), and
      pancreatic cancer risk in the Prostate, Lung, Colorectal and Ovarian Cancer
      Screening Trial prospective cohort. Our study included 101,449 participants aged
      52-78 years at baseline who completed both baseline questionnaire and a diet
      history questionnaire. Energy-adjusted DII (E-DII) scores were computed based on
      food and supplement intake. Cox proportional hazards models and time dependent
      Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals
      (CIs) with participants in the lowest E-DII quintile (most anti-inflammatory
      scores) as referent. After a median 8.5 years of follow-up, 328 pancreatic cancer
      cases were identified. E-DII scores were not associated with pancreatic cancer
      risk in the multivariable model (HRQ5vsQ1  = 0.94; 95% CI = 0.66-1.35; p-trend =
      0.43). Time significantly modified the association (p-interaction = 0.01). During
      follow up <4 years, there was suggestive evidence of an inverse association
      between E-DII and pancreatic cancer (HRQ5vsQ1  = 0.60; 95% CI = 0.35-1.02; p
      trend = 0.20) while there was a significant positive trend in the follow up >=4
      years (HRQ5vsQ1  = 1.31; 95% CI = 0.83-2.08; p-trend = 0.03). Similar results
      were observed for E-DII from food only. Our study does not support an association
      between inflammatory potential of diet and pancreatic cancer risk; however,
      heterogeneous results were obtained with different follow-up times. These
      divergent associations may result from the influences of undetected disease in
      the short-term.

PMID- 29355941
TI  - Cuckoos host range is associated positively with distribution range and
      negatively with evolutionary uniqueness.
AB  - The evolutionary distinctiveness (ED) score is a measure of phylogenetic
      isolation that quantifies the evolutionary uniqueness of a species. Here, we
      compared the ED score of parasitic and non-parasitic cuckoo species world-wide,
      to understand whether parental care or parasitism represents the largest amount
      of phylogenetic uniqueness. Next, we focused only on 46 cuckoo species
      characterized by brood parasitism with a known number of host species, and we
      explored the associations among ED score, number of host species and breeding
      range size for these species. We assessed these associations using phylogenetic
      generalized least squares (PGLS) models, taking into account the phylogenetic
      signal. Parasitic cuckoo species were not more unique in terms of ED than non
      parasitic species. However, we found a significant negative association between
      the evolutionary uniqueness and host range and a positive correlation between the
      number of host species and range size of parasitic cuckoos, probably suggesting a
      passive sampling of hosts by parasitic species as the breeding range broadens.
      The findings of this study showed that more generalist brood parasites occupied
      very different positions in a phylogenetic tree, suggesting that they have
      evolved independently within the Cuculiformes order. Finally, we demonstrated
      that specialist cuckoo species also represent the most evolutionarily unique
      species in the order of Cuculiformes.

PMID- 29355940
TI  - Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications
      for clinical use.
AB  - OBJECTIVES: The use of doxorubicin, an antineoplastic medication used for the
      treatment of cancers via mechanisms that prevent replication of cells or lead to
      their death, can result in damage to healthy cells as well as malignant. Among
      the affected cells are mesenchymal stem cells (MSCs), which are involved in the
      maintenance and repair of tissues in the body. This review explores the
      mechanisms of biological effects and damage attributed to doxorubicin on MSCs.
      The PubMed database was used as a source of literature for this review. KEY
      FINDINGS: Doxorubicin has the potential to lead to significant and irreversible
      damage to the human bone marrow environment, including MSCs. The primary known
      mechanism of these changes is through free radical damage and activation of
      apoptotic pathways. The presence of MSCs in culture or in vivo appears to either
      suppress or promote tumour growth. Interactions between doxorubicin and MSCs have
      the potential to increase chemotherapy resistance. SUMMARY: Doxorubicin-induced
      damage to MSCs is of concern clinically. However, MSCs also have been associated
      with resistance of tumour cells to drugs including doxorubicin. Further studies,
      particularly in vivo, are needed to provide consistent results of how the
      doxorubicin-induced changes to MSCs affect treatment and patient health.

PMID- 29355942
TI  - Anion exchanger 3 in dorsal root ganglion contributes to nerve injury-induced
      chronic mechanical allodynia and thermal hyperalgesia.
AB  - OBJECTIVE: To determine the role of anion exchanger 3 (AE3) in dorsal root
      ganglion (DRG) in nerve injury-induced chronic nociception in the rat. METHODS:
      Spared nerve injury (SNI) was used to induce neuropathic pain. Von Frey filaments
      and Hargreaves test were used to assess tactile allodynia and thermal
      hyperalgesia, respectively. Drugs were given by intrathecal administration.
      Western blotting was used to determine AE3 expression in DRG. KEY FINDINGS: SNI
      produced long-lasting mechanical allodynia and thermal hyperalgesia. AE3 was
      found in DRG of sham-operated rats. SNI enhanced baseline AE3 expression in L4
      and L5 DRGs at days 7 and 14, respectively. In contrast, SNI did not affect AE3
      expression in L6 DRG. AE3 expression returned to baseline levels 21 days after
      SNI. Intrathecal 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) (5-50
      MUg) pretreatment prevented SNI-induced allodynia and, at a lesser extent,
      hyperalgesia. Moreover, DIDS (50 MUg) reduced SNI-induced AE3 upregulation in L4,
      but not L5, DRGs. Intrathecal DIDS (5-50 MUg) or anti-AE3 antibody (1 MUg), but
      not vehicle, post-treatment (6 days) partially reversed SNI-induced allodynia and
      hyperalgesia. DIDS or anti-AE3 antibody post-treatment diminished SNI-induced AE3
      upregulation in L4 and L5 DRGs. CONCLUSIONS: Data suggest that AE3 is present in
      DRG and contributes to mechanical allodynia and thermal hyperalgesia in
      neuropathic rats.

PMID- 29355943
TI  - Antigastritis effects of Armillariella tabescens (Scop.) Sing. and the
      identification of its anti-inflammatory metabolites.
AB  - OBJECTIVES: This study demonstrates the biological and chemical analysis of the
      mushroom Armillariella tabescens (Scop.) Sing. (Tricholomataceae). METHODS:
      Chemical structures of the isolates were determined by 1D and 2D NMR, and ESI-MS,
      as well as comparison with previously reported data. All isolates were tested for
      anti-inflammatory effects based on their ability to inhibit LPS-stimulated nitric
      oxide (NO) production in RAW264.7 cells. KEY FINDINGS: We found that the MeOH
      extract of the fruiting bodies of A. tabescens showed antigastritis activity
      against ethanol-induced gastric damage in rats and notably reduced the gastric
      damage index compared to control in a concentration-dependent manner. Chemical
      investigation of the MeOH extract led to the isolation of four steroids (1-4),
      three alkaloids (5-7), two nucleic acids (8-9) and four fatty acids (10-13). This
      is the first study to report the identification of all isolates, except for
      compound 7, from A. tabescens. Compounds 1, 2, 3, 4 and 10 showed inhibition on
      LPS-stimulated NO production. Treatment with compound 10 inhibited expression of
      iNOS, COX-2, phospho-IKKalpha, IKKalpha, phospho-IkappaBalpha, IkappaBalpha and
      NF-kappa B in LPS-stimulated RAW264.7 cells. CONCLUSIONS: Compound 10 likely
      contributes to the health benefits of A. tabescens as an antigastritis agent
      through its anti-inflammatory effects.

PMID- 29355944
TI  - CrossTalk opposing view: Acute exercise does not elicit damage to the endothelial
      layer of systemic blood vessels in healthy individuals.

PMID- 29355945
TI  - Essential role of hippocampal noradrenaline in the regulation of spatial working
      memory and TDP-43 tissue pathology.
AB  - Extensive loss of noradrenaline-containing neurons and fibers is a nearly
      invariant feature of Alzheimer's Disease (AD). However, the exact noradrenergic
      contribution to cognitive and histopathological changes in AD is still unclear.
      Here, this issue was addressed following selective lesioning and intrahippocampal
      implantation of embryonic noradrenergic progenitors in developing rats. Starting
      from about 3 months and up to 12 months post-surgery, animals underwent
      behavioral tests to evaluate sensory-motor, as well as spatial learning and
      memory, followed by post-mortem morphometric analyses. At 9 months, Control,
      Lesioned and Lesion + Transplant animals exhibited equally efficient sensory
      motor and reference memory performance. Interestingly, working memory abilities
      were seen severely impaired in Lesion-only rats and fully recovered in
      Transplanted rats, and appeared partly lost again 2 months after ablation of the
      implanted neuroblasts. Morphological analyses confirmed the almost total lesion
      induced noradrenergic neuronal and terminal fiber loss, the near-normal
      reinnervation of the hippocampus promoted by the transplants, and its complete
      removal by the second lesion. Notably, the noradrenergic-rich transplants
      normalized also the nuclear expression of the transactive response DNA-binding
      protein 43 (TDP-43) in various hippocampal subregions, whose cytoplasmic (i.e.,
      pathological) occurrence appeared dramatically increased as a result of the
      lesions. Thus, integrity of ascending noradrenergic inputs to the hippocampus may
      be required for the regulation of specific aspects of learning and memory and to
      prevent TDP-43 tissue pathology.

PMID- 29355946
TI  - Rebuttal from Volker Adams.

PMID- 29355947
TI  - Corticotropin-releasing hormone-binding protein is up-regulated by brain-derived
      neurotrophic factor and is secreted in an activity-dependent manner in rat
      cerebral cortical neurons.
AB  - A recent study revealed that corticotropin-releasing hormone (CRH) in the
      cerebral cortex (CTX) plays a regulatory role in emotional behaviors in rodents.
      Given the functional interaction between brain-derived neurotrophic factor (BDNF)
      and the CRH-signaling pathway in the hypothalamic-pituitary-adrenal axis, we
      hypothesized that BDNF may regulate gene expression of CRH and its related
      molecules in the CTX. Findings of real-time quantitative PCR (RT-qPCR) indicated
      that stimulation of cultured rat cortical neurons with BDNF led to marked
      elevations in the mRNA levels of CRH and CRH-binding protein (CRH-BP). The BDNF
      induced up-regulation of CRH-BP mRNA was attenuated by inhibitors of tropomyosin
      related kinase (Trk) and MEK, but not by an inhibitor for PI3K and Phospholipase
      C gamma (PLCgamma). The up-regulation was partially blocked by an inhibitor of
      lysine-specific demethylase (KDM) 6B. Fluorescent imaging identified the
      vesicular pattern of pH-sensitive green fluorescent protein-fused CRH-BP (CRH-BP
      pHluorin), which co-localized with mCherry-tagged BDNF in cortical neurons. In
      addition, live-cell imaging detected drastic increases of pHluorin fluorescence
      in neurites upon membrane depolarization. Finally, we confirmed that tetrodotoxin
      partially attenuated the BDNF-induced up-regulation of CRH-BP mRNA, but not that
      of the protein. These observations indicate the following: In cortical neurons,
      BDNF led to gene expression of CRH-BP and CRH. TrkB, MEK, presumably ERK, and
      KDM6B are involved in the BDNF-induced gene expression of CRH-BP, and BDNF is
      able to induce the up-regulation in a neuronal activity-independent manner. It is
      suggested that CRH-BP is stored into BDNF-containing secretory granules in
      cortical neurons, and is secreted in response to membrane depolarization.

PMID- 29355949
TI  - CrossTalk proposal: Acute exercise elicits damage to the endothelial layer of
      systemic blood vessels in healthy individuals.

PMID- 29355948
TI  - Effects of Storage Conditions on Consumer and Chemical Assessments of Raw
      'Nonpareil' Almonds Over a Two-Year Period.
AB  - : Raw almonds are a major commodity, yet much is unknown about how storage
      conditions determine their shelf life. The storage stability, as measured by
      consumer assessments and chemical measures, of raw almonds was determined for
      samples stored in cardboard boxes and polypropylene packaging for 2 years at 4,
      15, 25, and 35  degrees C, and at 50% and 65% relative humidity (RH). Samples
      stored in unlined cartons always failed (>25% rejection) before their
      counterparts stored in polypropylene bags under identical environmental
      conditions. Models determined that polypropylene packaging (as opposed to unlined
      cardboard cartons) extended the time until sample rejection by more than 7
      months. Temperature and RH were both negatively associated with storage time
      until failure. Flavor was a greater contributor to consumer acceptability than
      texture or odor, while peroxide values and free fatty acids were of greater
      importance in predicting raw almond consumer quality than measures of conjugated
      dienes or 2-thiobarbituric acid-reactive substances. PRACTICAL APPLICATION: The
      results of this study will allow almond producers to determine packaging types
      and environmental storage conditions that provide shelf life of a specified time.

PMID- 29355950
TI  - Lansoprazole prevents the progression of liver fibrosis in non-alcoholic
      steatohepatitis model rats.
AB  - OBJECTIVES: We previously demonstrated that lansoprazole provided
      hepatoprotection in a drug-induced hepatitis animal model partially through the
      Nrf2/HO-1 pathway. Here, we examined whether lansoprazole could also provide
      hepatoprotection in a rat model of non-alcoholic steatohepatitis (NASH). METHODS:
      Six-week-old rats were fed a normal chow or a choline-deficient amino acid
      defined (CDAA) diet to establish a rat model of NASH. The groups fed a CDAA diet
      for 5 weeks were subcutaneously administered either a vehicle or a lansoprazole
      suspension for 4 weeks beginning the second week of the experiment. KEY FINDINGS:
      Bridging fibrosis was observed in the livers of almost all the NASH model rats
      (six of seven), but it was not always observed in NASH model rats (one of seven)
      continuously administered lansoprazole. The serum aspartate aminotransferase
      level elevated by the CDAA diet was significantly decreased following
      lansoprazole administration. Lansoprazole also increased the expression of Nrf2,
      but not HO-1, in the liver of NASH model rats. Lansoprazole decreased the level
      of activated TGF-beta protein. Furthermore, interleukin-6 gene and protein
      expression were decreased. CONCLUSIONS: Lansoprazole inhibits hepatic
      fibrogenesis, at least during the early stages, in CDAA diet-induced NASH model
      rats. The mechanisms might be associated with cytokine suppression but not the
      inhibition of reactive oxygen species.

PMID- 29355951
TI  - Evaluation of outpatient acupuncture for relief of pregnancy-related conditions.
AB  - BACKGROUND: Acupuncture is a non-pharmacological option to relieve pregnancy
      related complaints. OBJECTIVES: To critically appraise the best available
      evidence for the use of acupuncture in outpatient care. SEARCH STRATEGY: The
      MEDLINE, Cochrane Library, and Centre for Reviews and Dissemination databases
      were searched for English-language and German-language papers published from
      January 1980 to March 2017 using search terms related to pregnancy combined with
      'acupuncture'. SELECTION CRITERIA: Systematic reviews and randomized controlled
      trials (RCTs) comparing non-pharmacological treatments in unselected or low-risk
      pregnant women. DATA COLLECTION AND ANALYSIS: Quality was assessed using a
      checklist (A Measurement Tool to Assess Systematic Reviews) and the Cochrane risk
      of bias tool. Meta-analyses were also performed. MAIN RESULTS: High-quality
      systematic reviews (n=5) and RCTs with low risk of bias (n=3) were identified.
      The systematic reviews were based on single studies, with small sample sizes,
      that showed a benefit of acupuncture for evening pelvic pain; pelvic and low-back
      pain; nausea; functional disability; and sleep quality. Contradictory results
      were found in the RCTs regarding cesarean delivery; time to delivery; spontaneous
      labor; fetal distress; and Apgar score. Data pooling emphasized the heterogeneity
      of results. CONCLUSIONS: Evidence to support the use of acupuncture for relief of
      pregnancy-related conditions was limited.

PMID- 29355952
TI  - Impact of High Hydrostatic Pressure on the Shelling Efficacy, Physicochemical
      Properties, and Microstructure of Fresh Razor Clam (Sinonovacula constricta).
AB  - : The effects of high hydrostatic pressure (HHP) treatments (200, 300, and 400
      MPa for 1, 3, 5 and 10 min) on the shelling efficacy (the rate of shelling, the
      rate of integrity and yield of razor clam meat) and the physicochemical (drip
      loss, water-holding capacity, pH, conductivity, lipid oxidation, Ca2+ -ATPase
      activity, myofibrillar protein content), microbiological (total viable counts)
      and microstructural properties of fresh razor clam (Sinonovacula constricta) were
      investigated. HHP treatments significantly (P < 0.05) increased shelling
      efficiency, water-holding capacity, pH, conductivity, and lipid oxidation, and
      HHP-treated razor clam showed lower levels of microorganisms and drip loss than
      untreated razor clam. Levels of thiobarbituric acid reacting substances (TBA) in
      HHP-treated razor clam were greatly increased (up to 0.93 +/- 0.09 mg MDA/kg at
      400 MPa for 10 min) which was caused by the formation of hydroperoxides during
      HHP treatment. All HHP treatments were found to have adverse effects on the
      activity of Ca2+ -ATPase and the content of myofibrillar protein (MP), which
      might be due to the substantial damage to the tertiary structure of proteins at
      high pressure. Moreover, scanning electron microscopy (SEM) revealed the
      compaction of the muscle fibers and a decrease in the extracellular space with
      increasing pressure and holding time. This phenomenon was mainly correlated with
      the compaction of muscle fibers and denaturation, aggregation, and gelation of
      muscle protein triggered by high pressure. In general, HHP could be applied as a
      safe and effective nonthermal technology to produce high-quality shelled razor
      clam. PRACTICAL APPLICATION: High hydrostatic pressure (HHP) is now well known as
      a nonthermal processing technology and becoming increasingly acknowledged.
      However, it has not been widely applied to shell seafood due to its uncertain
      influence on its quality and shelling property. This study could provide valuable
      information regarding the shelling efficacy, physicochemical properties, and
      microstructure of razor clam treated by HHP. And it demonstrated that HHP showed
      a positive impact on quality of razor clam treated by HHP.

PMID- 29355953
TI  - Investigation into the Microstructure, Texture and Rheological Properties of
      Chocolate Ganache.
AB  - : Ganache is a mixture of chocolate and dairy. Although a popular confection,
      little is known about how it functions as a system. Objectives were to (1)
      determine if dairy fats and cocoa butter mix in ganache, (2) characterize ganache
      microstructure, and how structure affects texture and rheology, and (3) identify
      how changes in chocolate composition alter ganache. Textural analysis,
      differential scanning calorimetry, stress sweep tests, and microscopy were used
      to examine ganache formulations that varied in dairy source (cream or butter) or
      in solid fat content (SFC), composition or type of chocolate. Melting
      temperatures for all ganache formulations were lower than for chocolate,
      indicating that cream milk fat globules rupture during processing, and mix with
      cocoa butter. Altering the SFC of chocolate affected ganache hardness,
      spreadability, melting enthalpy, and resistance to deformation. Chocolate systems
      made with constant fat content and greater amounts of defatted cocoa powder
      relative to sugar or nonfat milk powder yielded ganache that was harder, less
      spreadable, and more resistant to deformation. Ganache made with commercially
      produced dark, milk, and white chocolates behaved similarly to model chocolate
      systems. Ganache attributes are affected by chocolate crystalline fat content in
      addition to particle phase volume-greater levels of cocoa powder, which is mostly
      insoluble, strengthens ganache structure, producing a firmer product, whereas
      greater levels of milk powder and sugar, which dissolve in the aqueous cream
      component, produce a softer ganache. PRACTICAL APPLICATION: Understanding how
      ganache functions as a system and how differences in chocolate composition affect
      its textural and rheological properties may allow for greater control over the
      desired characteristics of the final product. For example, this research shows
      how changing cocoa content of the chocolate affects ganache, which is useful when
      developing formulations involving chocolates with different cocoa percentages.
      There may also be cost saving implications; for example, using a chocolate with a
      harder cocoa butter may allow less total chocolate to be used in a formulation,
      while still achieving an appropriate texture.

PMID- 29355954
TI  - Comprehensive analysis of area-specific and time-dependent changes in gene
      expression in the motor cortex of macaque monkeys during recovery from spinal
      cord injury.
AB  - The present study aimed to assess the molecular bases of cortical compensatory
      mechanisms following spinal cord injury in primates. To accomplish this,
      comprehensive changes in gene expression were investigated in the bilateral
      primary motor cortex (M1), dorsal premotor cortex (PMd), and ventral premotor
      cortex (PMv) after a unilateral lesion of the lateral corticospinal tract (l
      CST). At 2 weeks after the lesion, a large number of genes exhibited altered
      expression levels in the contralesional M1, which is directly linked to the
      lesioned l-CST. Gene ontology and network analyses indicated that these changes
      in gene expression are involved in the atrophy and plasticity changes observed in
      neurons. Orchestrated gene expression changes were present when behavioral
      recovery was attained 3 months after the lesion, particularly among the bilateral
      premotor areas, and a large number of these genes are involved in plasticity.
      Moreover, several genes abundantly expressed in M1 of intact monkeys were
      upregulated in both the PMd and PMv after the l-CST lesion. These area-specific
      and time-dependent changes in gene expression may underlie the molecular
      mechanisms of functional recovery following a lesion of the l-CST.

PMID- 29355956
TI  - Rebuttal from Ryan M. Sapp and James M. Hagberg.

PMID- 29355957
TI  - Characterization of a New alpha-Linolenic Acid-Rich Oil: Eucommia ulmoides Seed
      Oil.
AB  - Eucommia ulmoides seed oil is the main byproduct of E. ulmoides cultivation. To
      better understand its functions, E. ulmoides seed oil is characterized
      comprehensively in this work. The composition of E. ulmoides seed,
      physicochemical properties, thermal properties, fatty acid composition,
      triacylglycerol (TAG) composition and Vitamin E composition of E. ulmoides seed
      oil were determined. The results show that the E. ulmoides seed contained about
      34.63% oil. The excellent physicochemical properties of E. ulmoides seed oil
      ensured it has a potential to be developed as an edible oil. The main fatty acids
      in E. ulmoides seed oil were linolenic acid (61.36%), oleic acid (17.02%), and
      linoleic acid (12.04%). HPLC-ELSD method determined that LnLnLn (37.99%), LnLnO
      (22.62%), LnLnL (14.5%), and LnLnP (8.78%) were the oil's major TAG components.
      The oil exhibited a unique thermal curve which contained 2 melting peaks at 
      38.45 and -22.22  degrees C, respectively. The total content of vitamin E in E.
      ulmoides seed oil was 190.96 mg/100g, which exist mainly in gamma-tocopherol and
      delta-tocopherol isomer. Overall, the results indicated that E. ulmoides seed oil
      is a promising oil in food, pharmaceutics, cosmetics and other nonfood
      industries.

PMID- 29355955
TI  - Complex neuroprotective and neurotoxic effects of histone deacetylases.
AB  - By their ability to shatter quality of life for both patients and caregivers,
      neurodegenerative diseases are the most devastating of human disorders.
      Unfortunately, there are no effective or long-terms treatments capable of slowing
      down the relentless loss of neurons in any of these diseases. One impediment is
      the lack of detailed knowledge of the molecular mechanisms underlying the
      processes of neurodegeneration. While some neurodegenerative diseases, such as
      Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are
      mostly sporadic in nature, driven by both environment and genetic susceptibility,
      many others, including Huntington's disease, spinocerebellar ataxias, and spinal
      bulbar muscular atrophy, are genetically inherited disorders. Surprisingly, given
      their different roots and etiologies, both sporadic and genetic neurodegenerative
      disorders have been linked to disease mechanisms involving histone deacetylase
      (HDAC) proteins, which consists of 18 family members with diverse functions.
      While most studies have implicated certain HDAC subtypes in promoting
      neurodegeneration, a substantial body of literature suggests that other HDAC
      proteins can preserve neuronal viability. Of particular interest, however, is the
      recent realization that a single HDAC subtype can have both neuroprotective and
      neurotoxic effects. Diverse mechanisms, beyond transcriptional regulation have
      been linked to these effects, including deacetylation of non-histone proteins,
      protein-protein interactions, post-translational modifications of the HDAC
      proteins themselves and direct interactions with disease proteins. The roles of
      these HDACs in both sporadic and genetic neurodegenerative diseases will be
      discussed in the current review.

PMID- 29355958
TI  - Canine pancreatic lipase immunoreactivity concentrations associated with
      intervertebral disc disease in 84 dogs.
AB  - OBJECTIVE: To determine the differences in serum canine pancreatic lipase
      immunoreactivity between dogs with intervertebral disc herniation and healthy
      control dogs. MATERIALS AND METHODS: Eighty-four client-owned dogs with
      intervertebral disc herniation, diagnosed by neurologic examination and imaging,
      and 18 healthy control dogs. Samples of whole blood were collected within 90
      minutes of admission. Serum canine pancreatic lipase immunoreactivity
      concentrations were measured by a commercial immunoassay and evaluated for
      association with intervertebral disc herniation, signalment, neurolocalisation
      and the preadmission administration of glucocorticosteriods or non-steroidal anti
      inflammatory drugs. RESULTS: Serum canine pancreatic lipase immunoreactivity
      concentrations were statistically increased in dogs with intervertebral disc
      herniation (P<0.01, n=38). A subgroup of dogs (19/38) with elevated canine
      pancreatic lipase immunoreactivity concentrations was re-evaluated between 2 and
      4 weeks later, and 15 had resolution of clinical signs and values less than 200
      MUg/L. Serum canine pancreatic lipase immunoreactivity concentrations were not
      significantly correlated with clinical gastrointestinal disease,
      neurolocalisation or the preadmission administration of corticosteroids or non
      steroidal anti-inflammatory drugs. CLINICAL SIGNIFICANCE: These results suggest
      that serum canine pancreatic lipase immunoreactivity concentrations are
      significantly elevated in dogs with intervertebral disc herniation.

PMID- 29355959
TI  - Optimized thoracoport design for the thoracoscopic procedure during minimally
      invasive esophagectomy.
AB  - Minimally invasive esophagectomy has several benefits as an effective alternative
      treatment for esophageal cancer. The three-phase esophageal resection may be the
      most popular approach to esophagectomy. Numerous thoracoport designs are
      available for the thoracoscopic procedure. The present study aims to contribute a
      distinctive three-port technique that is designed to minimize surgical trauma and
      facilitate operation during the thoracoscopic procedure. In this paper, we
      describe and demonstrate the details of the port design and each operation step.
      Based on our practical experience, the rational combination of the port design
      and instrument usage of the three-port technique makes the thorascopic procedure
      more convenient.

PMID- 29355960
TI  - Occupational radiation exposure and thyroid cancer incidence in a cohort of U.S.
      radiologic technologists, 1983-2013.
AB  - Although childhood exposure to ionizing radiation is a well-established risk
      factor for thyroid cancer, the risk associated with adulthood exposure remains
      unclear. We prospectively examined the association between cumulative, low-to
      moderate dose occupational radiation exposure to the thyroid and thyroid cancer
      incidence in the U.S. Radiologic Technologists cohort. The study included 89,897
      members who completed at least two of four mailed questionnaires and were cancer
      free at the time of the first questionnaire. Cumulative occupational thyroid
      radiation dose (mean = 57 mGy, range = 0-1,600 mGy) was estimated based on self
      reported work histories, historical data and, during the years 1960-1997, 783,000
      individual film badge measurements. During follow-up, we identified 476 thyroid
      cancer cases. We used Poisson regression to estimate excess relative risk of
      thyroid cancer per 100 milliGray (ERR/100 mGy) absorbed dose to the thyroid
      gland. After adjusting for attained age, sex, birth year, body mass index and
      pack-years smoked, we found no association between thyroid dose and thyroid
      cancer risk (ERR/100 mGy = -0.05, 95% CI <-0.10, 0.34). In this large cohort
      study of radiologic technologists, protracted, low-to-moderate dose ionizing
      radiation exposure to the thyroid gland in adulthood was not associated with an
      increased risk of thyroid cancer.

PMID- 29355961
TI  - Application of a Dielectric Barrier Discharge Atmospheric Cold Plasma (Dbd-Acp)
      for Eshcerichia Coli Inactivation in Apple Juice.
AB  - : Atmospheric cold plasma (ACP) is a promising non-thermal technology in food
      industry. In this study, a dielectric barrier discharge (DBD)-ACP exhibited
      strong bactericidal effect on Escherichia coli in apple juice. Under a 30 to 50 W
      input power, less than 40 s treatment time was required for DBD-ACP to result in
      3.98 to 4.34 log CFU/mL reduction of E. coli in apple juice. The inactivation
      behavior of ACP on E. coli was well described by the Weibull model. During the
      treatment, the cell membrane of E. coli was damaged severely by active species
      produced by plasma, such as hydrogen peroxide, ozone and nitrate. In addition,
      the ACP exposure had slight effect on the  degrees Brix, pH, titratable acidity
      (TA), color values, total phenolic content, and antioxidant capacity of apple
      juice. However, higher level of DBD-ACP treatment, 50 W for more than 10 s in
      this case, resulted in significant change of the pH, TA, color and total phenolic
      content of apple juice. The results in this study have provided insight in
      potential use of DBD-ACP as an alternative to thermal processing for fruit juices
      in food industry. PRACTICAL APPLICATION: Escherichia coli O157:H7 in apple juice
      is a potential risk for public health. This study demonstrated that 30 s cold
      plasma treatment resulted in more than 4 log CFU/mL reduction under 50 W, while
      the quality attributes of apple juice were not significantly affected. Therefore,
      cold plasma technology is a promising alternative substitute of traditional
      thermal processing for juice pasteurization.

PMID- 29355962
TI  - Alternative vascular constructs of lymph node flap transfer.
AB  - Vascularized lymph node transfer is a quite innovative physiological surgical
      procedure for the lymphedema treatment. Although is gaining more popularity due
      to its promising results, there are some concerns regarding difficult to harvest
      it and the potential risk of iatrogenic lymphedema. Here, we present alternative
      vascular constructs of lymph node flap for the treatment of lymphedema, which
      provide the benefits of a technically easier dissection and physiological
      reconstruction of the damaged lymphatics. Furthermore, we introduce a
      classification based on the flap vascular supply including six types of flaps and
      we provide the details of the surgical technique.

PMID- 29355963
TI  - Evolutionary history of mycorrhizal symbioses and global host plant diversity.
AB  - Contents Summary 1108 I. Introduction 1108 II. Mycorrhizal plant diversity at
      global and local scales 1108 III. Mycorrhizal evolution in plants: a brief update
      1111 IV. Conclusions and perspectives 1114 References 1114 SUMMARY: The majority
      of vascular plants are mycorrhizal: 72% are arbuscular mycorrhizal (AM), 2.0% are
      ectomycorrhizal (EcM), 1.5% are ericoid mycorrhizal and 10% are orchid
      mycorrhizal. Just 8% are completely nonmycorrhizal (NM), whereas 7% have
      inconsistent NM-AM associations. Most NM and NM-AM plants are nutritional
      specialists (e.g. carnivores and parasites) or habitat specialists (e.g.
      hydrophytes and epiphytes). Mycorrhizal associations are consistent in most
      families, but there are exceptions with complex roots (e.g. both EcM and AM). We
      recognize three waves of mycorrhizal evolution, starting with AM in early land
      plants, continuing in the Cretaceous with multiple new NM or EcM linages, ericoid
      and orchid mycorrhizas. The third wave, which is recent and ongoing, has resulted
      in root complexity linked to rapid plant diversification in biodiversity
      hotspots.

PMID- 29355964
TI  - Cytokinin signaling: from the ER or from the PM? That is the question!
AB  - Content Summary 47 I. Introduction 47 II. Historical outline 48 III. Recent
      developments 49 IV. Towards an integrative concept for cytokinin receptor
      signaling 54 Acknowledgements 57 References 57 SUMMARY: Cytokinin signaling plays
      an important role in plant growth and development, and therefore its molecular
      characteristics are under extensive study. One characteristic is the subcellular
      localization of cytokinin signal initiation. This localization determines both
      the pathway for hormone delivery to the receptor, as well as molecular aspects of
      signal transfer to the primary cellular targets. Subcellular sites for the onset
      of cytokinin signaling are still uncertain and experimental data are in part
      controversial. A few years ago, cytokinin receptors were shown to be localized
      predominantly in the membrane of the endoplasmic reticulum (ER) and to possess
      some features, such as their pH activity profile, typical for intracellular
      proteins. Very recently, new data corroborating the functionality of ER-located
      cytokinin receptors were reported. However, other work argued for cytokinin
      perception to occur at the plasma membrane (PM). Here, we discuss in detail these
      partially conflicting data and present an integrative model for cytokinin
      perception and signaling. In our opinion, the prevailing evidence argues for the
      ER being the predominant site of cytokinin signal perception but also that signal
      initiation at the PM might be relevant in some circumstances as well. The roles
      of these pathways in long-distance, paracrine and autocrine cytokinin signaling
      are discussed.

PMID- 29355965
TI  - In response to socioeconomic disparities and comorbidities, not race, affect
      salivary gland malignancy survival outcomes.

PMID- 29355966
TI  - Predictors for 30-day readmission after pulmonary resection for lung cancer.
AB  - BACKGROUND: The purpose of this study was to assess the rate, cause, and factors
      associated with readmissions following pulmonary resection for lung cancer and
      their relationship with 90-day mortality. METHODS: A prospective cohort study was
      conducted of 379 patients who underwent surgery for lung cancer at the university
      hospitals Granada, Spain between 2012 and 2016. RESULTS: The rate of readmissions
      within 30 postoperative days was 6.2%. The most common reason for readmission was
      subcutaneous emphysema (21.7%), pneumonia (13%), and pleural empyema (8.5%). A
      higher probability of requiring urgent readmission was associated with a higher
      Charlson index (OR 2.0,95% confidence interval 1.50-2.67, P = 0.001); peripheral
      arterial vasculopathy (OR 4.8, 95%CI 1.27-18.85, P = 0.021); a history of stroke
      (OR 8.2, 95%CI 1.08-62.37, P = 0.04); postoperative atelectasis (OR 4.7, 95%CI
      1.21-18.64, P = 0.026); and air leaks (OR 12.6, 95%CI 4.10-38.91, P = 0.001).The
      prediction multivariable model for readmission represents an area under the curve
      (ROC) of 0.90. Mortality at 90 postoperative days in the group of readmitted
      patients was 13% versus 1.5 for the group of patients who did not require
      readmission (P < 0.001). CONCLUSIONS: The factors predictive for readmission can
      help design individualized outpatient follow-up plans and programs for the
      reduction of readmissions.

PMID- 29355967
TI  - Understanding the determinants of adolescent nutrition in Bangladesh.
AB  - Evidence on the nutritional status and diets of adolescents in low- and middle
      income countries is scant. We characterized the nutritional status (body mass
      index Z-scores (BMIZs)) and nutrient intakes of adolescent boys and girls in
      rural areas in Bangladesh using the 2011-2012 BIHS data, used regression models
      to identify the socioeconomic determinants of these outcomes, and household fixed
      effects models to assess whether the gap between boys and girls changed with
      women's education and empowerment and household wealth. The adolescents' BMIZ and
      adequacy of their nutrient intakes were suboptimal. Gender differences varied by
      outcome and were not systematically in favor of boys. Household wealth was
      associated with higher BMIZ and probability of adequate energy and micronutrient
      intakes. Women's education and empowerment were mostly not associated with the
      study outcomes and did not modify gender differences. There is an urgent need to
      invest in improving the diets of adolescent boys and girls in Bangladesh. The
      limited role of women's education and empowerment in improving adolescent
      nutrition suggests that resources may be too constrained. It may also reflect
      deeply rooted beliefs about adolescent nutrition and differences between boys and
      girls that would need to be addressed to improve their nutrition.

PMID- 29355968
TI  - The unfolding landscape of the congenital myasthenic syndromes.
AB  - Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the
      safety margin of neuromuscular transmission is impaired by one or more specific
      mechanisms. Since the advent of next-generation sequencing methods, the discovery
      of novel CMS targets and phenotypes has proceeded at an accelerated rate. Here,
      we review the current classification of CMS and describe our findings in five of
      these targets identified and investigated in our laboratory in the past 5 years.
      Defects in LRP4 hinder synaptic development and maintenance; the defects in PREPL
      are predicted to diminish filling of the synaptic vesicle with acetylcholine; and
      defects in SNAP25, Munc13-1, and synaptotbrevin-1 impede synaptic vesicle
      exocytosis.

PMID- 29355969
TI  - Primary liver sarcomas in the modern era: Resection or transplantation?
AB  - BACKGROUND AND OBJECTIVES: Primary liver sarcomas (PLS) are rare. Published
      series are limited by small numbers of patients. METHODS: We reviewed the
      National Cancer Database (2004-2014) for patients who underwent surgical
      resection of PLS. RESULTS: Of 237 patients identified, the majority were female
      (60.8%), with median age of 52 years. Histologies were: epithelioid
      hemangioendothelioma (n = 67), angiosarcoma (n = 64), leiomyosarcoma (n = 33),
      embryonal rhabdomyosarcoma (n = 31), carcinosarcoma (n = 16), giant cell sarcoma
      (n = 14), spindle cell sarcoma (n = 12). Ninety-seven (40.9%) patients underwent
      lobectomies or extended lobectomies, 41 patients (17.3%) underwent
      transplantation. Surgical margins were negative in 82.9%. Tumors were well
      differentiated in 11.3%. Histology type correlated with outcome with the best
      prognosis for epithelioid hemangioendothelioma (OS: not reached, similar for
      resection and transplantation) and the worst for angiosarcoma (OS:16.6 mo with
      resection; 6 mo with transplantation; P = 0.04). Resections with microscopically
      negative margins were associated with improved survival (58.7 vs 11.3 mo for
      positive margins; P < 0.001). Chemotherapy and radiation therapy were used in a
      minority of patients (32.9% and 4.3% respectively) with no improvement in
      outcomes. CONCLUSIONS: Both hepatic resection and liver transplantation can be
      associated with long term survival for selected primary liver sarcomas such as
      epitheliod hemangioendotheliomas. Histology type and the ability to resect the
      tumor with negative margins correlate with outcomes and the decision to operate
      should be carefully weighed for subtypes with particularly dismal prognosis such
      as angiosarcomas.

PMID- 29355971
TI  - Leiomyoma in the nasal cavity of a dog.
AB  - A 7-year-old, 34-kg, neutered male Labrador retriever was presented with a 1-year
      history of intermittent sneezing with occasional left-sided epistaxis. CT
      revealed a mass in the left nasal cavity. Histopathological analysis of
      rhinoscopy-guided tissue biopsies was consistent with chronic necrotic and
      ulcerative rhinitis. Surgical debridement by ventral rhinotomy was subsequently
      performed and histopathological diagnosis was leiomyoma. Complete resolution of
      the nasal discharge and reduced sneezing frequency were observed after surgery.
      Fourteen months postoperatively, CT detected no regrowth of the mass.

PMID- 29355970
TI  - Comparison of open and closed abdomen techniques for the delivery of
      intraperitoneal pemetrexed using a murine model.
AB  - BACKGROUND AND OBJECTIVES: Pemetrexed is an appealing agent to use for
      cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC).
      However, the optimal method of pemetrexed delivery still remains undefined. Using
      a murine model, we compared the use of open and closed abdomen techniques on the
      absorption of intraperitoneal (IP) pemetrexed in different compartments. METHODS:
      Eleven Sprague-Dawley rats were submitted to a fixed dose of IP pemetrexed (1000
      mg/m2 ) at a perfusion temperature of 40 degrees C during 25 min according to two
      techniques: open and closed. At the end of perfusion, samples in different
      compartments were harvested and the concentrations of pemetrexed were measured by
      high performance liquid chromatography. RESULTS: Absorption of IP pemetrexed in
      portal and systemic blood was significantly higher using the open compared to the
      closed abdomen technique (93.17 vs 52.50 ug/mL, P < 0.001) and (76.26 vs 51.65
      ug/mL, P < 0.001), respectively. No difference was found between the two
      techniques on the peritoneal tissue concentration of pemetrexed (18.07 vs 19.17
      ug/g, P = 0.51). CONCLUSION: Peritoneal absorption of pemetrexed is not modified
      by the use of either technique. However, systemic concentrations of pemetrexed
      increased using the open technique, suggesting it could increase systemic
      toxicity.

PMID- 29355972
TI  - High intraspecific genome diversity in the model arbuscular mycorrhizal symbiont
      Rhizophagus irregularis.
AB  - Arbuscular mycorrhizal fungi (AMF) are known to improve plant fitness through the
      establishment of mycorrhizal symbioses. Genetic and phenotypic variations among
      closely related AMF isolates can significantly affect plant growth, but the
      genomic changes underlying this variability are unclear. To address this issue,
      we improved the genome assembly and gene annotation of the model strain
      Rhizophagus irregularis DAOM197198, and compared its gene content with five
      isolates of R. irregularis sampled in the same field. All isolates harbor
      striking genome variations, with large numbers of isolate-specific genes, gene
      family expansions, and evidence of interisolate genetic exchange. The observed
      variability affects all gene ontology terms and PFAM protein domains, as well as
      putative mycorrhiza-induced small secreted effector-like proteins and other
      symbiosis differentially expressed genes. High variability is also found in
      active transposable elements. Overall, these findings indicate a substantial
      divergence in the functioning capacity of isolates harvested from the same field,
      and thus their genetic potential for adaptation to biotic and abiotic changes.
      Our data also provide a first glimpse into the genome diversity that resides
      within natural populations of these symbionts, and open avenues for future
      analyses of plant-AMF interactions that link AMF genome variation with plant
      phenotype and fitness.

PMID- 29355973
TI  - Innervation status in chronic vocal fold paralysis and implications for laryngeal
      reinnervation.
AB  - OBJECTIVE: Treatment options for symptomatic unilateral vocal fold paralysis
      (VFP) include vocal fold augmentation, laryngeal framework surgery, and laryngeal
      reinnervation. Laryngeal reinnervation (LR) has been suggested to provide "tone"
      to the paralyzed VF. This implies a loss of tone as a result of denervation
      without reinnervation. We performed laryngeal electromyography (LEMG) in patients
      with chronic VFP to understand the innervation status associated with a
      chronically paralyzed vocal fold. STUDY DESIGN: Retrospective review of LEMG data
      in adult patients with chronic VFP from January 2009 to December 2014. METHODS:
      LEMG was performed at least 6 months after-onset of VFP. Qualitative LEMG,
      quantitative LEMG, and adductory synkinesis testing were performed, and the
      parameters were collected. RESULTS: Twenty-seven vocal folds were studied (23
      unilateral VFP and 2 bilateral VFP). Average age was 59 +/- 17 years. The median
      duration from recurrent laryngeal nerve injury to LEMG was 8.5 months (range 6-90
      months). The majority of patients, 24 of 27 (89%), had motor unit potentials
      during phonation tasks on LEMG, and only 3 of 27 (11%) patients were electrically
      silent. Quantitative LEMG showed 287.8 mean turns per second (normal >= 400).
      Motor unit configuration was normal in 12 of 27 (44%), polyphasic in 12 of 27
      (44%), and absent in the electrically silent patients. Adductory synkinesis was
      found in 6 of 20 (30%) patients. CONCLUSION: Chronic vocal fold paralysis is
      infrequently associated with absent motor-unit recruitment, indicating some
      degree of preserved innervation and/or reinnervation in these patients. LEMG
      should be part of the routine workup for chronic VFP prior to consideration of
      LR. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1628-1633, 2018.

PMID- 29355974
TI  - The mediating role of coping strategy in the association between family
      functioning and nonsuicidal self-injury among Taiwanese adolescents.
AB  - OBJECTIVE: Nock's (2009) integrated theoretical model suggests that both
      intrapersonal and interpersonal factors contribute to the development of
      nonsuicidal self-injury (NSSI). Based on this model, the present study examined
      the roles of family functioning and coping strategy in predicting NSSI, as well
      as the mediating effect of coping strategy in the relationship between family
      functioning and NSSI. Gender differences on the associations of these variables
      were also examined. METHOD: A sample of 1,989 secondary school students (52.0%
      females) in Taiwan was assessed by self-report measures of perceived family
      functioning, coping strategy, and NSSI. RESULTS: Results showed that both family
      functioning and avoidance/emotion-focused coping strategy predicted NSSI.
      Additionally, the association between family functioning and NSSI was mediated by
      avoidance/emotion-focused coping strategy. Gender differences were not found on
      the associations among these study variables. CONCLUSIONS: These data provided
      evidences that the Nock's (2009) integrated theoretical model may help to explain
      how coping strategy mediates the effect of family functioning on NSSI. The
      implications of the findings for future research and intervention were discussed.

PMID- 29355975
TI  - C-reactive protein as a marker of the surgical stress reduction within an ERAS
      protocol (Enhanced Recovery After Surgery) in colorectal surgery: A prospective
      cohort study.
AB  - BACKGROUND: The aim of this study is to evaluate the effectiveness of an Enhanced
      Recovery After Surgery Protocol (ERAS) in relation to reduce the Systemic
      Inflammatory Response (SIR) to surgery using C-reactive protein (CRP) in the
      first (POD1), second (POD2) and third (POD3) postoperative day. METHODS: We
      enrolled 121 patients (ERAS group) that underwent elective colorectal surgery
      with ERAS, and compared them with 135 patients (preERAS group) that had undergone
      surgery prior to the implementation. We made a univariate analysis to compare the
      CRP values in POD1, POD2, and POD3 between preERAS/ERAS group, laparoscopic/open
      surgery and the presence or not of Clavien Dindo complications. Multivariable
      lineal regression was used to assess if the ERAS had a decreasing effect on the
      CRP in POD1, POD2, and POD3, and was adjusted by age, male sex, use of
      laparoscopy, and complications. RESULTS: The presence of complications was
      independently associated with an increase in CRP values in POD1, POD2, and POD3.
      Laparoscopy in POD1 and POD2, and ERAS in POD2 was independently associated with
      a decrease in CRP values. CONCLUSION: The analysis shows an increase in SIR
      measured as a CRP value in those patients that had complications. The SIR
      decreased with laparoscopy in POD1 and POD2 and with ERAS in POD2.

PMID- 29355976
TI  - Clinical evidence of prevention strategies for capecitabine-induced hand-foot
      syndrome.
AB  - Hand-foot syndrome (HFS) is the most common adverse effect of capecitabine
      containing chemotherapy. The purpose of this study was to assess the efficacies
      of various prevention and treatment strategies for capecitabine-induced HFS.
      Searches of the PubMed and Embase databases were performed to identify relevant
      studies. The risk ratio (RR) with the corresponding 95% confidence interval (CI)
      was used as an effect measure to evaluate the efficacies of these prevention and
      treatment strategies. Publication bias was evaluated using Begg's and Egger's
      tests. Overall and subgroup analyses were conducted. All statistical analyses
      were conducted with Stata software version 12.0. Seventeen eligible studies were
      included. Our results indicated that celecoxib was significantly associated with
      a lower incidence of grade >=2 capecitabine-induced HFS without heterogeneity (RR
      = 0.43, 95% CI = 0.23-0.81, I2  = 0.0%). However, pyridoxine and topical
      urea/lactic acid were not effective toward preventing capecitabine-induced grade
      1, 2, 3, >=1 or >=2 HFS. Moreover, pyridoxine was not effective in treating
      capecitabine-induced HFS. Similar results were obtained by subgroup analysis. Our
      results indicate that celecoxib has potential prophylactic efficacy for
      capecitabine-induced HFS. However, pyridoxine and topical urea/lactic acid are
      not associated with a decrease in the incidence of capecitabine-induced HFS.

PMID- 29355977
TI  - Helicobacter pylori infection is associated with favorable outcome in advanced
      gastric cancer patients treated with S-1 adjuvant chemotherapy.
AB  - BACKGROUND AND OBJECTIVES: Limited information exists regarding beneficial
      effects of Helicobacter pylori. To examine the effect in advanced gastric cancer,
      we compared survival for patients treated with surgery-only or adjuvant
      chemotherapy on the basis of H. pylori infection status. METHODS: A cohort of 491
      patients who underwent R0 resection for locally advanced gastric cancer between
      2000 and 2009 at 12 institutions in northern Japan was included. H. pylori
      infection status, was assessed from paraffin-embedded formalin-fixed samples.
      Overall survival (OS) and disease-free survival (DFS) in surgery-only (Surgery)
      and adjuvant chemotherapy (S-1) groups were analyzed. A propensity score matching
      was employed to correct for confounding factors by indication. RESULTS: H. pylori
      infection was positive in 175 patients and negative in 316 patients. H. pylori
      positive patients showed significantly better survival than H. pylori-negative
      patients in both OS (hazard ratio [HR] 0.593, 95% confidence interval [CI] 0.417
      0.843; P = 0.003]) and DFS (HR 0.679, 95%CI 0.492-0.937; P = 0.018). Propensity
      score matching further confirmed that S-1 was virtually only effective when
      tumors were H. pylori-positive. CONCLUSIONS: The favorable outcome of H. pylori
      positive patients implies that the host immune system is modulated by H. pylori
      enhancing the chemotherapeutic efficacy.

PMID- 29355978
TI  - Perception and duration of pain after office-based vocal fold injection
      augmentation.
AB  - OBJECTIVES/HYPOTHESIS: In-office laryngology procedures are important in the
      treatment of voice and swallowing disorders. Patient tolerance determines which
      procedures can be performed without sedation or formal anesthesia. This study
      examines pain perception during and after in-office vocal fold injection
      augmentation. STUDY DESIGN: Prospective cohort study. METHODS: Patients scheduled
      for office-based vocal fold injection augmentation were prospectively enrolled at
      an academic voice center. The short-form McGill Pain Questionnaire was
      administered before, during, and after the procedure and on postprocedure days 1,
      3, and 7. Pre- and postprocedure vital signs were recorded and heart rate was
      continuously monitored. Telephone questionnaires were completed on postprocedure
      days 1 and 3. RESULTS: Forty-five patients consented to participate in our study
      (24 males, mean age 61 years). Most patients experienced mild to moderate pain
      with increasing heart rate during the procedure. Pain remained or increased 20
      minutes after the procedure and improved but persisted for 1 day. Sensory and
      affective discomfort was endorsed by the majority. A minority of patients
      experienced bruising and changes in swallowing with diet modification for 3 days
      after the procedure. Sixteen percent had discomfort after 1 week. CONCLUSIONS:
      This is the first prospective study examining patient perception of pain during
      and after in-office injection augmentation using a validated scale and pain
      descriptors with extended follow-up. The results may offer guidance for patient
      counseling, consent, and treatment to improve tolerance and success. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:929-934, 2018.

PMID- 29355979
TI  - Preoperative coagulation abnormalities as a risk factor for adverse events after
      pancreas surgery.
AB  - OBJECTIVE: To determine whether elevated INR or PTT values predicted 30-day
      postoperative adverse events following elective pancreatectomy. METHODS: The
      American college of surgeons national surgical quality improvement program (ACS
      NSQIP) database was used to identify 14 747 patients undergoing elective
      pancreatectomy from 2005 to 2013. The association of elevated INR or PTT with 30
      day postoperative outcomes of morbidity and mortality was examined using
      multivariate logistic regression analysis. RESULTS: The overall 30-day mortality
      rate increased from 1.8% to 3.3% from the control to the high INR or PTT group (P
      = <0.001). An elevated INR/PTT increased the odds for bleeding requiring
      transfusion, superficial SSI, sepsis, unplanned intubation or >48 h on a
      ventilator, cardiac arrest or myocardial infarction, acute renal failure, return
      to the OR, and prolonged length of stay. With the exception of superficial SSI,
      multivariate logistic regression models revealed that these same events remained
      statistically significant after controlling for potential confounders.
      CONCLUSION: Prolonged bleeding times (high INR/PTT) is associated with increased
      mortality and adverse outcomes after pancreas surgery. A patient's coagulation
      profile may serve as a risk stratification tool to identify higher risk patients
      that require more resources.

PMID- 29355980
TI  - Branch order regression for modeling brain vasculature.
AB  - PURPOSE: Many biological objects, including neuronal dendrites, blood
      vasculature, airways, phylogenetic trees, produce tree structured data. Current
      methods of analysis either ignore the complex structure of trees or use distance
      based methods which limit the scope of multivariate modeling. METHODS: We propose
      a branching process model which enables analysis of both the branching structure
      and associated properties. Our novel parametrization preserves an important
      aspect of tree structure, namely its branch order. The model is amenable to
      standard methods of analysis, like generalized linear/additive models. RESULTS:
      The model fit the distribution of the observed data quite well when applied to a
      collection of 98 brain artery systems. The estimated probability of branching
      decreases log linearly with branch order. Likewise, the average diameter of
      arteries decreases, while average length increases with branch order. Frontal
      arterial branches are on average longer and thinner than those in the back at
      equivalent branch orders. A mechanistic arterial branching model based on
      Poiseuille's blood flow law, which uses vessel length and diameter information,
      fit the observed branching structure significantly better. This model is further
      improved by including branch order, suggesting viscoelastic flow impacts
      branching in narrower vessels. CONCLUSION: After adjustment for branch order,
      brain arterial branching probabilities decreased significantly with age and
      length, but increased with diameter. Arteries become thicker and branch less
      frequently with increasing age, but the age effect decreases with branch order.

PMID- 29355981
TI  - Examination of the skin barrier repair/wound healing process using a living skin
      equivalent model and matrix-assisted laser desorption-ionization-mass
      spectrometry imaging.
AB  - OBJECTIVE: Examination of the skin barrier repair/wound healing process using a
      living skin equivalent (LSE) model and matrix-assisted laser
      desorption/ionization-mass spectrometry imaging (MALDI-MSI) to identify lipids
      directly involved as potential biomarkers. These biomarkers may be used to
      determine whether an in vivo wound is going to heal for example if infected.
      METHODS: An in vitro LSE model was wounded with a scalpel blade and assessed at
      day 4 post-wounding by histology and MALDI-MSI. Samples were sectioned at wound
      site and were either formalin-fixed paraffin-embedded (FFPE) for histology or
      snapped frozen (FF) for MSI analysis. RESULTS: The combination of using an in
      vitro wounded skin model with MSI allowed the identification of lipids involved
      in the skin barrier repair/wound healing process. The technique was able to
      highlight lipids directly in the wound site and distinguish differences in lipid
      distribution between the epidermis and wound site. CONCLUSION: This novel method
      of coupling an in vitro LSE with MSI allowed in-depth molecular analysis of the
      skin barrier repair/wound healing process. The technique allowed the
      identification of lipids directly involved in the skin barrier repair/wound
      healing process, indicating these biomarkers may be potentially be used within
      the clinic. These biomarkers will help to determine, which stage of the skin
      barrier repair/wound healing process the wound is in to provide the best
      treatment.

PMID- 29355982
TI  - iPad applications that required a range of motor skills promoted motor
      coordination in children commencing primary school.
AB  - BACKGROUND/AIM: Children are reported to spend less time engaged in outdoor
      activity and object-related play than in the past. The increased use and mobility
      of technology, and the ease of use of tablet devices are some of the factors that
      have contributed to these changes. Concern has been raised that the use of such
      screen and surface devices in very young children is reducing their fine motor
      skill development. We examined the effectiveness of iPad applications that
      required specific motor skills designed to improve fine motor skills. METHOD: We
      conducted a two-group non-randomised controlled trial with two pre-primary
      classrooms (53 children; 5-6 years) in an Australian co-educational school, using
      a pre- and post-test design. The effectiveness of 30 minutes daily use of
      specific iPad applications for 9 weeks was compared with a control class.
      Children completed the Beery Developmental Test of Visual Motor Integration (VMI)
      and observation checklist, the Shore Handwriting Screen, and self-care items from
      the Hawaii Early Learning Profile. RESULTS: On post testing, the experimental
      group made a statistically and clinically significant improvement on the VMI
      motor coordination standard scores with a moderate clinical effect size (P <
      0.001; d = 0.67). Children's occupational performance in daily tasks also
      improved. CONCLUSION: Preliminary evidence was gained for using the iPad, with
      these motor skill-specific applications as an intervention in occupational
      therapy practice and as part of at home or school play.

PMID- 29355984
TI  - PCR evaluation of selected vector-borne pathogens in dogs with pericardial
      effusion.
AB  - OBJECTIVES: To investigate evidence for selected vector-borne pathogen infections
      in dogs with pericardial effusion living in a Mediterranean area in which several
      canine vector-borne diseases are endemic. MATERIALS AND METHODS: Archived EDTA
      blood (n=68) and pericardial fluid samples (n=58) from dogs with pericardial
      effusion (n=68) were included. Dogs without pericardial effusion examined for
      other reasons were included as controls (n=60). Pericardial effusion was
      classified as neoplastic in 40 dogs, idiopathic in 23 dogs and of unknown
      aetiology in 5 dogs. Real-time PCR was performed for Leishmania infantum,
      Ehrlichia/Anaplasma species, Hepatozoon canis, Babesia species, Rickettsia
      species and Bartonella species, and sequencing of PCR products from positive
      samples was used to confirm species specificity. RESULTS: Vector-borne pathogens
      were found in 18 dogs: 16 of 68 dogs with pericardial effusion (23.5%) and two of
      60 control dogs (3.3%). Positive dogs demonstrated DNA of Leishmania infantum
      (n=7), Anaplasma platys (n=2, one dog coinfected with Leishmania infantum),
      Babesia canis (n=5), Babesia gibsoni (n=3) and Hepatozoon canis (n=2). Vector
      borne pathogens were more commonly detected among dogs with pericardial effusion
      than controls (P=0.001). There was no relationship between aetiology of the
      pericardial effusion and evidence of vector-borne pathogens (P=0.932). CLINICAL
      SIGNIFICANCE: Vector-borne pathogens are often detected in dogs with pericardial
      effusion and require further investigation, especially in dogs with idiopathic
      pericardial effusion. PCR can provide additional information about the potential
      role of vector-borne pathogens in dogs with pericardial effusion living in
      endemic areas.

PMID- 29355983
TI  - Early-injection laryngoplasty may lower risk of thyroplasty: A systematic review
      and meta-analysis.
AB  - OBJECTIVE: To determine whether injection laryngoplasty within 6 months following
      the onset of unilateral vocal fold paralysis (UVFP) decreases the rate of
      permanent thyroplasty in adults. DATA SOURCES: Search strategies created by a
      medical librarian were implemented in multiple online research databases. REVIEW
      METHODS: Inclusion and exclusion criteria were designed to capture randomized
      clinical trials and cohort studies examining adults with UVFP who received
      injection laryngoplasty early in the course of treatment, within 6 months of
      onset, or who were observed. The primary outcome was the rate of thyroplasty. The
      Newcastle-Ottawa scale was used to assess quality of included cohort studies.
      Random effects meta-analysis was used to calculate an overall relative risk (RR).
      Heterogeneity was evaluated with the I2 statistic. RESULTS: The search strategy
      resulted in 1,177 studies, of which four cohort studies remained for meta
      analysis after applying inclusion and exclusion criteria. All studies were rated
      as 9 of 9 on the Newcastle-Ottawa scale. Meta-analysis of 275 patients with UVFP
      revealed that the overall pooled RR of undergoing thyroplasty in those receiving
      an early injection was 0.25 (95% confidence interval 0.14-0.45) compared to
      conservative management (late or no injection). The I2 overall was 62.4%.
      CONCLUSION: Otolaryngologists should offer injection laryngoplasty to patients
      with a diagnosis of UVFP within 6 months of diagnosis (recommendation based on
      grade C evidence with a preponderance of benefit over harm). Laryngoscope,
      128:935-940, 2018.

PMID- 29355985
TI  - Identification of T-cell epitopes from benzylpenicillin conjugated to human serum
      albumin and implication in penicillin allergy.
AB  - BACKGROUND: There is in vitro evidence that T cells from allergic patients react
      to benzylpenicillin-human serum albumin (BP-HSA) bioconjugates. Our group has
      recently shown the existence of naive CD4+ T cells recognizing BP-HSA in healthy
      donors. However, BP-haptenated peptides from HSA participating in the
      immunization of allergic patients have never been identified. The purpose of the
      present study is to identify immunodominant BP-haptenated peptides from HSA
      involved in immunization of patients to BP and to refine the frequency
      calculation of naive CD4+ T cells recognizing BP. METHODS: Co-cultures were
      established with CD4+ T cells from non-allergic donors and mature autologous
      dendritic cells (DCs) loaded with BP-HSA or BP-haptenated peptides from HSA. The
      CD4+ T-cell response specific for BP-HSA or for individual BP-haptenated peptides
      was measured using an interferon-gamma (IFN-gamma) ELISpot assay. The frequency
      of BP-specific CD4+ T cells was then calculated using the Poisson distribution.
      BP-HSA and BP-haptenated peptides recognition by allergic patients was evaluated
      on peripheral blood mononuclear cells (PBMCs) using a lymphocyte transformation
      test (LTT). RESULTS: Results showed that BP-HSA and BP-haptenated peptides were
      recognized by naive T cells from 15/16 and 13/14 tested healthy donors,
      respectively. Most donors responded to 3 peptides with BP covalently bound on
      lysines 159, 212, and 525. Two of these benzylpenicilloylated peptides (lysines
      159 and 525) were also found to induce PBMCs proliferation in patients with
      allergic reaction to penicillins. CONCLUSION: This study identifies and
      characterizes for the first time the BP-haptenated peptides from HSA involved in
      the immunization of patients to penicillins.

PMID- 29355986
TI  - The role of negative cognitions, emotion regulation strategies, and attachment
      style in complex post-traumatic stress disorder: Implications for new and
      existing therapies.
AB  - OBJECTIVE: We set out to investigate the association between negative trauma
      related cognitions, emotional regulation strategies, and attachment style and
      complex post-traumatic stress disorder (CPTSD). As the evidence regarding the
      treatment of CPTSD is emerging, investigating psychological factors that are
      associated with CPTSD can inform the adaptation or the development of effective
      interventions for CPTSD. METHOD: A cross-sectional design was employed. Measures
      of CPTSD, negative trauma-related cognitions, emotion regulation strategies, and
      attachment style were completed by a British clinical sample of trauma-exposed
      patients (N = 171). Logistic regression analysis was used to assess the
      predictive utility of these psychological factors on diagnosis of CPTSD as
      compared to PTSD. RESULTS: It was found that the most important factor in the
      diagnosis of CPTSD was negative trauma-related cognitions about the self,
      followed by attachment anxiety, and expressive suppression. CONCLUSIONS:
      Targeting negative thoughts and attachment representations while promoting skills
      acquisition in emotional regulation hold promise in the treatment of CPTSD.
      Further research is required on the development of appropriate models to treat
      CPTSD that tackle skills deficit in these areas. PRACTITIONER POINTS: Results
      suggest that cognitive-behavioural interventions might be useful for the
      treatment of CPTSD. Targeting negative thoughts and attachment representations
      while promoting skills acquisition in emotional regulation hold promise in the
      treatment of CPTSD.

PMID- 29355987
TI  - Staged surgical treatment of extremity lymphedema with dual gastroepiploic
      vascularized lymph node transfers followed by suction-assisted lipectomy-A
      prospective study.
AB  - BACKGROUND: Both physiologic and excisional procedures have been described for
      the treatment of lymphedema. However, there exist few reports that combine these
      procedures. The objective of this study was to evaluate the effectiveness of
      combining vascularized lymph node transfer (VLNT) with suction-assisted lipectomy
      (SAL) in a staged manner for the treatment of extremity lymphedema. METHODS:
      Patients with unilateral late stage II lymphedema (International Society of
      Lymphology), who consented to staged surgical treatment, were evaluated
      prospectively. Between 2014 and 2015, 12 female patients with upper (n = 6) or
      lower (n = 6) extremity lymphedema completed the treatment protocol. Primary
      outcomes evaluated included limb size and number of infectious episodes. In
      addition, compression garment usage was analyzed. RESULTS: The overall
      circumference reduction rate was on average 37.9% after VLNT and increased to
      96.4% after SAL. While all patients had experienced at least one infectious
      episode prior to surgical treatment, only one patient did so after VLNT and none
      after SAL. All patients were able to eventually discontinue compression therapy.
      CONCLUSION: VLNT followed by SAL can allow patients with late Stage II lymphedema
      achieve near normal limb size and eradication of infectious episodes. At follow
      up, these desirable outcomes were maintained well after discontinuation of
      compression therapy.

PMID- 29355988
TI  - Variation in practice patterns and outcomes across United Network for Organ
      Sharing allocation regions.
AB  - BACKGROUND: The number of heart transplants performed is limited by organ
      availability and is managed by the United Network for Organ Sharing (UNOS).
      Efforts are underway to make organ disbursement more equitable as demand
      increases. HYPOTHESIS: Significant variation exists in contemporary patterns of
      care, wait times, and outcomes among patients undergoing heart transplantation
      across UNOS regions. METHODS: We identified adult patients undergoing first,
      single-organ heart transplantation between January 2006 and December 2014 in the
      UNOS dataset and compared sociodemographic and clinical profiles, wait times, use
      of mechanical circulatory support (MCS), status at time of transplantation, and 1
      year survival across UNOS regions. RESULTS: We analyzed 17 096 patients
      undergoing heart transplantation. There were no differences in age, sex, renal
      function, and peripheral vascular resistance across regions; however, there was 3
      fold variation in median wait time (range, 48-166 days) across UNOS regions.
      Proportion of patients undergoing transplantation with status 1A ranged from 36%
      to 79% across regions (P < 0.01), and percentage of patients hospitalized at time
      of transplantation varied from 41% to 98%. There was also marked variation in MCS
      and inotrope utilization (28%-57% and 25%-58%, respectively; P < 0.001). Durable
      ventricular assist device implantation varied from 20% to 44% (P < 0.001), and
      intra-aortic balloon pump utilization ranged from 4% to 18%. CONCLUSIONS: Marked
      differences exist in patterns of care across UNOS regions that generally trend
      with differences in waitlist time. Novel policy initiatives are required to
      address disparities in access to allografts and ensure equitable and efficient
      allocation of organs.

PMID- 29355989
TI  - Modern separation techniques coupled to high performance mass spectrometry for
      glycolipid analysis.
AB  - Glycolipids (GLs), involved in biological processes and pathologies, such as
      viral, neurodegenerative and oncogenic transformations are in the focus of
      research related to method development for structural analysis. This review
      highlights modern separation techniques coupled to mass spectrometry (MS) for the
      investigation of GLs from various biological matrices. First section is dedicated
      to methods, which, although provide the separation in a non-liquid phase, are
      able to supply important data on the composition of complex mixtures. While
      classical thin layer chromatography (TLC) is useful for MS analyses of the
      fractionated samples, ultramodern ion mobility (IMS) characterized by high
      reproducibility facilitates to discover minor species and to apply low sample
      amounts, in addition to providing conformational separation with isomer
      discrimination. Second section highlights the advantages, applications and
      limitations of liquid-based separation techniques such as high performance liquid
      chromatography (HPLC) and hydrophilic interaction liquid chromatography (HILIC)
      in direct or indirect coupling to MS for glycolipidomics surveys. The on- and off
      line capillary electrophoresis (CE) MS, offering a remarkable separation
      efficiency of GLs is also presented and critically assessed from the technical
      and application perspective in the final part of the review.

PMID- 29355991
TI  - A functionally personalized boundary condition model to improve estimates of
      fractional flow reserve with CT (CT-FFR).
AB  - PURPOSE: The purpose of this study is to develop and evaluate a functionally
      personalized boundary condition (BC) model for estimating the fractional flow
      reserve (FFR) from coronary computed tomography angiography (CCTA) using flow
      simulation (CT-FFR). MATERIALS AND METHODS: The CCTA data of 90 subjects with
      subsequent invasive FFR in 123 lesions within 21 days (range: 0-83) were
      retrospectively collected. We developed a functionally personalized BC model
      accounting specifically for the coronary microvascular resistance dependency on
      the coronary outlets pressure suggested by several physiological studies. We used
      the proposed model to estimate the hemodynamic significance of coronary lesions
      with an open-loop physics-based flow simulation. We generated three-dimensional
      (3D) coronary tree geometries using automatic software and corrected manually
      where required. We evaluated the improvement in CT-FFR estimates achieved using a
      functionally personalized BC model over anatomically personalized BC model using
      k-fold cross-validation. RESULTS: The functionally personalized BC model slightly
      improved CT-FFR specificity in determining hemodynamic significance of lesions
      with intermediate diameter stenosis (30%-70%, N = 72), compared to the
      anatomically personalized model lesions with invasive FFR measurements as the
      reference (sensitivity/specificity: 0.882/0.79 vs 0.882/0.763). For the entire
      set of 123 coronary lesions, the functionally personalized BC model improved only
      the area under the curve (AUC) but not the sensitivity/specificity in determining
      the hemodynamic significance of lesions, compared to the anatomically
      personalized model (AUC: 0.884 vs 0.875, sensitivity/specificity: 0.848/0.805).
      CONCLUSION: The functionally personalized BC model has the potential to improve
      the quality of CT-FFR estimates compared to an anatomically personalized BC
      model.

PMID- 29355992
TI  - Antithrombotic therapy in peripheral artery disease: A review of the EUCLID trial
      results and current ongoing trials.
AB  - In addition to risk-factor modification, antithrombotic therapy is the hallmark
      of management to reduce cardiovascular ischemic events in patients with
      peripheral artery disease (PAD). Currently, the guidelines recommend long-term
      antiplatelet therapy with aspirin or clopidogrel in this patient population to
      reduce myocardial infarction, stroke, and vascular death. Past outcomes studies
      have shown some benefit of ticagrelor, another antiplatelet agent, as compared
      with clopidogrel in patients with coronary disease and concomitant PAD. However,
      most recently, the Examining Use of Ticagrelor in Peripheral Artery Disease
      (EUCLID) trial has shown no additional benefit of ticagrelor over clopidogrel. In
      this trial, a minority of patients had concomitant coronary artery disease,
      making it unique to previous studies. The EUCLID trial's evidence of neutrality
      between clopidogrel and ticagrelor sheds light into the complexity of studying
      the PAD population and the continued need to meticulously design trials to
      investigate the optimal therapies. The topics that will be discussed in this
      review include the role of antiplatelet therapy in the management of patients
      with PAD, a review of the EUCLID trial results and the important factors to be
      considered in interpreting the surprising results, and promising recent ongoing
      clinical trials assessing therapies in the treatment of patients with PAD.

PMID- 29355990
TI  - A sticky end for gastrointestinal helminths; the role of the mucus barrier.
AB  - Gastrointestinal (GI) nematodes are a group of successful multicellular parasites
      that have evolved to coexist within the intestinal niche of multiple species. It
      is estimated that over 10% of the world's population are chronically infected by
      GI nematodes, making this group of parasitic nematodes a major burden to global
      health. Despite the large number of affected individuals, there are few effective
      treatments to eradicate these infections. Research into GI nematode infections
      has primarily focused on defining the immunological and pathological consequences
      on host protection. One important but neglected aspect of host protection is
      mucus, and the concept that mucus is just a simple barrier is no longer tenable.
      In fact, mucus is a highly regulated and dynamic-secreted matrix, underpinned by
      a physical hydrated network of highly glycosylated mucins, which is increasingly
      recognized to have a key protective role against GI nematode infections.
      Unravelling the complex interplay between mucins, the underlying epithelium and
      immune cells during infection are a major challenge and are required to fully
      define the protective role of the mucus barrier. This review summarizes the
      current state of knowledge on mucins and the mucus barrier during GI nematode
      infections, with particular focus on murine models of infection.

PMID- 29355993
TI  - Relationships between Army nursing practice environments and patient outcomes.
AB  - Favorable nursing practice environments have been associated with lower patient
      mortality, failure to rescue, nurse-administered medication errors, infections,
      patient complaints, and patient falls. Favorable environments have also been
      associated with higher nurse-reported care quality and patient satisfaction in
      civilian hospitals. However, limited information exists on the relationship
      between favorable nursing practice environments and positive outcomes in military
      facilities. Using 4 years of secondary data collected from 45 units in 10 Army
      hospitals, generalized estimating equations were used to test the associations
      between nurses' scores on the Practice Environment Scale of the Nursing Work
      Index (PES-NWI) and patient outcomes of falls with and without injury, medication
      administration errors with and without harm, and patient experience. Four
      significant associations were found between the PES-NWI subscales and the patient
      outcomes under study. The Staffing and Resource Adequacy subscale was
      significantly associated with patient falls, the Collegial Nurse Physician
      Relations subscale was significantly associated with the rate of nurse
      administered medication errors, and the Nursing Foundations for Quality Care and
      Collegial Nurse Physician Relations subscales were both significantly associated
      with patient experience with nursing care. As in civilian hospitals, favorable
      nursing practice environment was associated with improved patient outcomes within
      these military nursing units.

PMID- 29355994
TI  - Quantitative analysis of sesquiterpenes and comparison of three Curcuma wenyujin
      herbal medicines by micro matrix solid phase dispersion coupled with MEEKC.
AB  - A simple, efficient and environmental friendly method was proposed for
      determining five sesquiterpenoids of Curcuma wenyujin by MSPD extraction coupled
      with MEEKC separation. Molecular sieve was applied as a solid support for
      extraction of sesquiterpenoids for the first time. Various parameters affecting
      extraction and separation efficiency were investigated. The optimized conditions
      involved dispersing sample (200 mg) with 200 mg of TS-1 for 150 s and using 1000
      MUL of methanol to elute five target analytes. Finally, they were well separated
      by using a running buffer containing 1.3% SDS, 5.0% 1-butanol, 0.5% ethyl acetate
      and 10% acetonitrile in 10 mM borate buffer at pH 9.0. Consequently, the
      developed method was fully validated and successfully applied to determine the
      five sesquiterpenoids including curdine, curcumenol, germacrone, furanodiene and
      beta-elemene in Curcuma wenyujin origin's Chinese herbal medicines. Furthermore,
      hierarchical cluster analysis was performed based on the contents of target
      compounds for distinguishing steamed and non-steamed drugs. The present study
      provided a promising method for fast investigation and discrimination of chemical
      difference in steam & non-steamed Chinese medicines from Curcuma wenyujin origin.

PMID- 29355995
TI  - Dysphagia secondary to focal inflammatory myopathy and consequent dorsiflexion of
      the tongue in a dog.
AB  - A 14-month-old female pitbull terrier mix was presented for evaluation of
      dysphagia of 8 months' duration secondary to intermittent dorsiflexion of the
      tongue apex. Physical and neurological examinations were unremarkable with the
      exception of the dorsiflexed tongue. Serum creatine kinase activity was increased
      (703 IU/L, reference interval: 55 to 257 IU/L), and electromyography of the
      tongue demonstrated areas of fibrillation potentials. Histopathology of the
      tongue showed myopathic changes with excessive variability in myofibre size and
      endomysial fibrosis. Cytochemical stains verified mixed mononuclear cells
      throughout the endomysium and perimysium consistent with a chronic inflammatory
      myopathy. No improvement was reported following prednisone administration;
      although the dog was able to prehend kibble, it needed assistance when drinking
      water. This is the first report documenting a focal lingual myopathy in a non
      corgi breed and highlights the utility of determining creatine kinase activity
      and obtaining tongue biopsies when warranted in dysphagic animals.

PMID- 29355996
TI  - Lymphatic vessel diameter in female pelvic cancer-related lower extremity
      lymphedematous limbs.
AB  - BACKGROUND: Lymphaticovenular anastomosis (LVA) has become one of the useful
      surgical treatments for compression-refractory lower extremity lymphedema (LEL).
      It is important to anastomose larger lymphatic vessels with abundant lymph flows
      in LVA surgery. This study aimed to clarify factors associated with lymphatic
      vessel diameter. METHODS: One hundred thirty-four LEL patients who underwent pre
      operative indocyanine green (ICG) lymphography and LVA from June 2009 to August
      2014 in a single institution were included in this retrospective observational
      study. Clinical, ICG lymphography, and intraoperative findings were collected
      from medical charts. A lymphatic vessel with external diameters of 0.5 mm or
      larger was defined as a large lymphatic vessel (LLV). Independent factors
      associated with LLV were identified using logistic regression analysis. RESULTS:
      Nine hundred sixty-two lymphatic vessels were identified, among which 438 (45.5%)
      were LLVs. Independent factors associated with LLV were older age (odds ration
      [OR], 1.408; 95% confidence interval [CI], 1.026-1.931; P = 0.034), positive
      history of radiation (OR, 1.634; 95%CI 1.228-2.173; P = 0.001), incision site in
      the thigh/lower leg compared with in the groin (OR, 1.617/1.685; 95%CI 1.076
      2.432/1.148-2.473; P = 0.021/0.008). Inverse associations were observed in S
      region/D-region on ICG lymphography compared with L-region (OR, 0.537/0.048;
      95%CI, 0.397-0.726/0.006-0.371; P < 0.001/0.004). CONCLUSIONS: D-region on ICG
      lymphography had the lowest OR to find LLV, representing that lymphatic vessels
      found in D-region on ICG lymphography would be significantly smaller than those
      in L-region. In LVA surgery, D-region should be avoided.

PMID- 29355998
TI  - Prevalence and disease associations in feline thrombocytopenia: a retrospective
      study of 194 cases.
AB  - OBJECTIVES: To assess the prevalence of thrombocytopenia in a referral population
      of cats in the UK, to identify disease processes associated with thrombocytopenia
      and to assess the proportion of thrombocytopenic cats that tested positive for
      feline leukaemia virus or feline immunodeficiency virus. MATERIALS AND METHODS:
      Retrospective analysis of medical records at a UK referral hospital. Cats were
      grouped by mechanism of thrombocytopenia and disease process (where known).
      RESULTS: Prevalence of thrombocytopenia was 5.9%. The most common disease
      processes associated with thrombocytopenia were haematological or infectious
      disease and neoplasia; 11% of thrombocytopenic cats tested were positive for
      feline leukaemia virus, which is lower than reported previously. Cats presenting
      with unexplained haemorrhage had significantly lower platelet counts than other
      thrombocytopenic cats. Primary immune-mediated thrombocytopenia was less commonly
      diagnosed than in dogs and associated with the most severe platelet depletion in
      this study. CLINICAL SIGNIFICANCE: Thrombocytopenia in cats may be more prevalent
      than previously reported and severe thrombocytopenia may be associated with
      spontaneous haemorrhage. Severe thrombocytopenia in cats appears less commonly
      immune-mediated than in dogs. Thrombocytopenia did not appear to be associated
      with retroviral infections.

PMID- 29355997
TI  - Effect of body mass index on survival after sudden cardiac arrest.
AB  - BACKGROUND: Although elevated body mass index (BMI) is a risk factor for cardiac
      disease, patients with elevated BMI have better survival in the context of severe
      illness, a phenomenon termed the "obesity paradox." HYPOTHESIS: Higher BMI is
      associated with lower mortality in sudden cardiac arrest (SCA) survivors.
      METHODS: Data were collected on 1433 post-SCA patients, discharged alive from the
      hospitals of the University of Pittsburgh Medical Center between 2002 and 2012.
      Of those, 1298 patients with documented BMI during the index hospitalization and
      follow-up data constituted the study cohort. RESULTS: In the overall cohort, 30
      patients were underweight (BMI <18.5 kg/m2 ), 312 had normal weight (BMI 18.5
      24.9 kg/m2 ), 417 were overweight (BMI 25.0-29.9 kg/m2 ), and 539 were obese (BMI
      >=30 kg/m2 ). As expected, the prevalence of coronary artery disease, myocardial
      infarction, diabetes mellitus, and hypertension increased significantly with
      increasing BMI. Over a median follow-up of 3.6 years, 602 (46%) patients died.
      Despite higher prevalence of cardiovascular comorbidities in more obese patients,
      a higher BMI was associated with lower all-cause mortality on univariate analysis
      (hazard ratio: 0.86 per increase by 1 BMI category, 95% confidence interval: 0.78
      0.94, P = 0.002) and multivariate analysis after adjusting for unbalanced
      baseline comorbidities (hazard ratio: 0.86 per increase by 1 BMI category, 95%
      confidence interval: 0.77-0.96, P = 0.009). CONCLUSIONS: Higher BMI is associated
      with lower all-cause mortality in survivors of SCA, suggesting that the obesity
      paradox applies to the post-arrest population. Further investigation into its
      mechanisms may inform the management of post-SCA patients.

PMID- 29355999
TI  - Reassessment of cardiovascular parameters and comorbidities in implantable
      cardioverter-defibrillator patients at the time of first replacement.
AB  - BACKGROUND: Guidelines provide extensive recommendations regarding implantable
      cardioverter-defibrillator (ICD) implantation. However, ICD replacement at the
      time of battery depletion is rarely studied. HYPOTHESIS: Our objectives were to
      identify patients at high-risk of death after ICD replacement, with a
      reassessment of changes in risk factors and comorbidities at the time of
      replacement, and to determine predictors for subsequent mortality. METHODS:
      Patients undergoing ICD replacement for regular battery depletion were selected
      from a prospective single-center ICD registry. Both at implant and replacement, 3
      demographic parameters, 9 cardiovascular parameters, 5 comorbidities, and 4
      laboratory parameters were collected. Cox proportional hazard analyses were used.
      RESULTS: We included 308 patients who were predominantly male (86%) with a median
      age at ICD replacement of 66 years. Replacement was performed 65 months
      (interquartile range, 52-91) after implantation. Median follow-up after
      replacement was 41 months, during which 82 patients (27%) died. Multivariable
      analysis revealed 4 independent predictors of mortality after ICD replacement:
      age/year (hazard ratio [HR]: 1.05, 95% confidence interval [CI]: 1.03-1.08, P =
      0.01), worsening heart failure by 1 class (HR: 1.53, 95% CI: 1.15-2.03, P =
      0.003), presence of left bundle branch block (HR: 1.98, 95% CI: 1.22-3.23, P =
      0.006), and ICD therapy prior to replacement (HR: 2.22, 95% CI: 1.37-3.58, P =
      0.001). Incorporated into a dichotomous score, they strongly correlated with
      mortality at 5 years after replacement (5% with 0 parameters, 15% with 1
      parameter, and 30%-55% with >2 parameters). CONCLUSIONS: Focused reassessment of
      selected patient characteristics at the time of ICD replacement correlates with
      subsequent mortality and can impact decision making at this point in time.

PMID- 29356000
TI  - Generalized reactions during skin testing with clindamycin in drug
      hypersensitivity: a report of 3 cases and review of the literature.
AB  - BACKGROUND: The diagnostic approach to drug hypersensitivity includes a detailed
      medical history, clinical examination, and skin testing and/or oral challenge
      with a culprit or alternative drug, depending on the type of reaction and the
      suspected drugs. Although skin testing is considered to be rather safe, cutaneous
      and systemic, including fatal, reactions have been described. OBJECTIVES: To
      report 3 cases with generalized delayed reactions after skin testing with
      clindamycin, and to review the existing literature. METHODS: Thorough clinical
      examination, blood tests and prick, intradermal and patch tests were performed in
      3 patients. RESULTS: All patients experienced generalized maculopapular exanthema
      after intradermal and patch testing with clindamycin and amoxicillin in the first
      patient, and clindamycin alone in the second and third patient. None of the
      patients showed immediate reactions to skin tests, while positive intradermal
      reactions after 24 h to amoxicillin and clindamycin were observed in the first
      patient, and positive intradermal reactions after 24 h to clindamycin were
      observed in the second and third patients. CONCLUSIONS: Skin testing with
      clindamycin in the diagnosis of drug hypersensitivity carries some risk of
      adverse reactions. A stepwise and individual diagnostic work-up, considering
      potential risk factors, and testing in a specialized centre with emergency
      equipment available is highly recommended.

PMID- 29356002
TI  - Towards a theory of functional magnetic resonance spectroscopy (fMRS): A meta
      analysis and discussion of using MRS to measure changes in neurotransmitters in
      real time.
AB  - Proton magnetic resonance spectroscopy is a powerful tool to investigate
      neurochemistry and physiology in vivo. Recently researchers have started to use
      MRS to measure neurotransmitter changes related to neural activity, so called
      functional MRS (fMRS). Particular interest has been placed on measuring glutamate
      changes associated with neural function, but differences are reported in the size
      of changes seen. This review discusses fMRS, and includes meta-analyses of the
      relative size of glutamate changes seen in fMRS, and the impact experimental
      design and stimulus paradigm may have. On average glutamate was found to increase
      by 6.97% (+/-1.739%) in response to neural activation. However, factors of
      experimental design may have a large impact on the size of these changes. For
      example an increase of 4.749% (+/-1.45%) is seen in block studies compared to an
      increase of 13.429% (+/-3.59) in studies using event related paradigms. The
      stimulus being investigated also seems to play a role with prolonged visual
      stimuli showing a small mean increase in glutamate of 2.318% (+/-1.227%) while at
      the other extreme, pain stimuli show a mean stimulation effect of 14.458% (+/
      3.736%). These differences are discussed with regards to possible physiologic
      interpretations, as well experimental design implications.

PMID- 29356001
TI  - Early versus delayed invasive strategy for intermediate- and high-risk acute
      coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design
      and rationale of the EARLY randomized trial.
AB  - According to recent literature, pretreatment with a P2Y12 ADP receptor antagonist
      before coronary angiography appears no longer suitable in non-ST-segment
      elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit
      ratio. Optimal delay of the invasive strategy in this specific context is
      unknown. We hypothesize that without P2Y12 ADP receptor antagonist pretreatment,
      a very early invasive strategy may be beneficial. The EARLY trial (Early or
      Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment
      Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized,
      controlled, open-label, 2-parallel-group study that plans to enroll 740 patients.
      Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is
      made and an invasive strategy intended. Patients are randomized in a 1:1 ratio.
      In the control group, a delayed strategy is adopted, with the coronary
      angiography taking place between 12 and 72 hours after randomization. In the
      experimental group, a very early invasive strategy is performed within 2 hours. A
      loading dose of a P2Y12 ADP receptor antagonist is given at the time of
      intervention in both groups. Recruitment began in September 2016 (n = 558
      patients as of October 2017). The primary endpoint is the composite of
      cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial
      aims to demonstrate the superiority of a very early invasive strategy compared
      with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed
      without P2Y12 ADP receptor antagonist pretreatment.

PMID- 29356003
TI  - Principles of cross-network communication in human resting state fMRI.
AB  - Directed signaling among and within the large-scale networks of the human brain
      is functionally critical. Recent advances in our understanding of spontaneous
      fluctuations of the fMRI BOLD signal have provided strategies to study the
      spatial-temporal properties of directed signaling at infra-slow frequencies.
      Herein we explore the relationship between two canonical systems of the human
      brain, the default mode network (DMN) and the dorsal attention network (DAN)
      whose anti-correlated relationship is well known but poorly understood. We find
      that within the DMN, activity moves from retrosplenial to prefrontal cortex
      whereas in the DAN activity moves from the frontal eye fields to the parietal
      cortex. Bi-directional communication between the two networks occurs via their
      earliest elements (i.e., from the retrosplenial cortex of the DMN to the frontal
      eye fields of the DAN). This framework for network communication appears to
      generalize across all networks providing an expanded basis for understanding
      human brain function.

PMID- 29356004
TI  - Training switching focus with a mobile-application by a patient suffering from
      AVH, a case report.
AB  - Auditory verbal hallucinations complicate many psychiatric disorders.
      Antipsychotic medication is effective in the majority, but a significant minority
      experiences high burden from resistant hallucinations. Here, we aim to improve
      executive control, in an attempt to decrease burden from hallucinations. We
      describe the use of a cognitive trainings app by a young woman with highly
      resistant hallucinations. With modest training, a significant decrease in the
      duration of hallucinations was reached. Possibilities of this training technique
      are discussed.

PMID- 29356005
TI  - How to get a left-ear advantage: A technical review of assessing brain asymmetry
      with dichotic listening.
AB  - The dichotic-listening paradigm with verbal stimuli is a widely employed
      behavioral task for the assessment of hemispheric asymmetry for speech and
      language processing. Participants with assumed left-hemispheric dominance report
      the right-ear stimulus with higher probability than the left-ear stimulus.
      However, there is substantial between-subject and trial-to-trial variability
      observed in the paradigm, motivating scrutiny of the task set-up and theoretical
      models. Here, we give an in-depth discussion of specific features of stimulus
      material and experimental parameters, as well as the conditions of
      stimulus/response selection, which explain a significant proportion of intra- and
      inter-individual variability. Carefully considering these factors should be at
      the heart of any experimental planning when using the dichotic-listening paradigm
      to achieve an optimal testing situation for measuring laterality and avoid
      confounds in between-subject and between-group comparisons.

PMID- 29356006
TI  - The functional and structural asymmetries of the superior temporal sulcus.
AB  - The superior temporal sulcus (STS) is an anatomical structure that increasingly
      interests researchers. This structure appears to receive multisensory input and
      is involved in several perceptual and cognitive core functions, such as speech
      perception, audiovisual integration, (biological) motion processing and theory of
      mind capacities. In addition, the superior temporal sulcus is not only one of the
      longest sulci of the brain, but it also shows marked functional and structural
      asymmetries, some of which have only been found in humans. To explore the
      functional-structural relationships of these asymmetries in more detail, this
      study combines functional and structural magnetic resonance imaging. Using a
      speech perception task, an audiovisual integration task, and a theory of mind
      task, this study again demonstrated an involvement of the STS in these processes,
      with an expected strong leftward asymmetry for the speech perception task.
      Furthermore, this study confirmed the earlier described, human-specific
      asymmetries, namely that the left STS is longer than the right STS and that the
      right STS is deeper than the left STS. However, this study did not find any
      relationship between these structural asymmetries and the detected brain
      activations or their functional asymmetries. This can, on the other hand, give
      further support to the notion that the structural asymmetry of the STS is not
      directly related to the functional asymmetry of the speech perception and the
      language system as a whole, but that it may have other causes and functions.

PMID- 29356007
TI  - The research evidence for schizophrenia as a neurodevelopmental disorder.
AB  - Schizophrenia is a neurodevelopmental disorder that starts very early. In this
      review we describe the empirical evidence for the neurodevelopmental model.
      First, by outlining the roots of psychological research that laid the foundation
      of the model. Thereafter, describing cognitive dysfunction observed in
      schizophrenia, and the course of cognitive functioning in the illness. Then,
      research findings that speak for and studies that speak against the view that
      schizophrenia is a degenerative process is discussed. We find that there is ample
      evidence that cognitive disturbance is a core element in schizophrenia. However,
      we have limited understanding of what initiates the abnormal development. This
      the paper ends with pointing out some of the factors that may trigger the deviant
      neurocognitive development in schizophrenia.

PMID- 29356008
TI  - How can genetics help understand the relationship between cognitive dysfunction
      and schizophrenia?
AB  - Despite the consistent finding that cognitive dysfunction is a core
      characteristic of schizophrenia (SCZ), little is known about the underlying
      pathophysiology. Recent progress in human genetics, driven by large genome-wide
      association studies (GWAS), has provided new data about the genetic architecture
      of complex human traits, including cognition and SCZ. Novel analytical tools have
      provided unprecedented opportunities to leverage the large amount of information
      from GWAS. Here we review the latest findings related to genetic architecture and
      risk genes of SCZ and cognitive functions, and recent findings of overlapping
      genetic factors. The recent GWAS of SCZ implicate over 100 risk gene loci, each
      with a small effect. A similar genetic architecture seems to be present in
      cognitive domains, suggesting that these phenotypes are highly polygenic.
      Further, GWAS have revealed more than 20 gene loci associated with cognitive
      traits, including intelligence, general cognition (g-factor), reaction time and
      verbal-numerical reasoning. Several gene loci have been implicated in educational
      attainment, a proxy measure of cognitive function. Recently, overlapping gene
      loci were found between education and SCZ, and between SCZ and cognitive traits,
      suggesting common genetic risk between SCZ and cognitive dysfunction.
      Mathematical modeling of GWAS of cognition and SCZ indicate that only a fraction
      of the heritability is identified. The evidence suggests a polygenic architecture
      for SCZ and cognitive functions, and a large degree of shared genetic risk. This
      indicates novel molecular genetic mechanisms and strengthens the notion that SCZ
      is more likely a part of the normal distribution and not a separate entity.

PMID- 29356010
TI  - A life in academia: My career in brief.
AB  - In this article I have summarized some of the main trends and topics of my
      research career, spanning a time period of 50 years, from its start as a master
      student at the Department of Psychology, University of Uppsala, Sweden to seeing
      the end of a long career, now at the University of Bergen, Norway. This journey
      has, apart from having been a journey across various disciplines and topics in
      experimental psychology, psychophysiology and neuropsychology, functional
      neuroimaging and cognitive neuroscience, also been a social class journey for me
      personally. I describe my academic career from my arrival as a young student at
      the University of Uppsala, Sweden in the late 1960s to my graduation as PhD in
      1977 at the age of 29 years, brief postdoc period at the University of
      Pennsylvania, USA, and finally professor at the University of Bergen, Norway. The
      article focuses on my view of the research and research findings during these
      years, including studies of hemispheric asymmetry, dyslexia and language,
      dichotic listening, fMRI, and during the last years, studies of auditory
      hallucinations in schizophrenia. I have collaborated with numerous people, both
      nationally and internationally over the years, far too many to mention in a space
      limited overview article. I apologize for this, and wish that I had time and
      space to mention all the fantastic colleagues and friends that I have met during
      my career. This article is what I recall of dates, places, encounters, etc., and
      any errors and misunderstandings are entirely due to my far from perfect memory,
      for which I also apologize.

PMID- 29356009
TI  - Hallucinations, neuroplasticity, and prediction errors in schizophrenia.
AB  - Auditory hallucinations, a hallmark symptom of psychosis, are experienced by most
      people with a diagnosis of schizophrenia at some point in their illness. Auditory
      hallucinations can be understood as a failure in predictive coding, whereby
      abnormalities in sensory/perceptual processing combine with biased cognitive
      processes to result in a dampening of normal prediction error signaling. In this
      paper, we used a roving mismatch negativity (MMN) paradigm to optimize evaluation
      of prediction error signaling and short-term neuroplasticity in 30 people with
      schizophrenia (n = 16 with and n = 14 without recent auditory hallucinations) and
      20 healthy comparison participants. The recent hallucinations group exhibited an
      abnormal roving MMN profile [F(2,27) = 3.98, p = 0.03], significantly reduced
      prediction error signaling [t(28) = -2.25, p = 0.03], and a trend for diminished
      short-term neuroplasticity [t(28) = 1.80, p = 0.08]. There were no statistically
      significant differences between the healthy comparison group and the combined
      schizophrenia group on any of the roving MMN indices. These findings are
      consistent with a predictive coding account of hallucinations in schizophrenia,
      which posits reduced prediction error signaling in those who are prone to
      hallucinations. These results also suggest that plasticity-mediated formation and
      online updating of predictive coding models may also be disrupted in individuals
      with recent hallucinations.

PMID- 29356011
TI  - The right-side perceptual bias in aging determined in a laboratory setting and
      during a virtual driving task.
AB  - Spatial perceptual rightward bias which was originally described in Dichotic
      Listening studies seems to be a general phenomenon. This bias is age dependent,
      being evident in children with developing executive functions, and emerging again
      at older age as a function of aging and the declining executive functions. In the
      two studies presented here we compared the performance of young and elderly
      adults in spatial divided attention tasks with auditory and visual stimuli when
      the stimulus detection performance was measured in separate sessions in a
      laboratory setting (Study I), to performance when the same types of stimuli were
      mixed with a task in which the subject's primary objective was to drive a car in
      a virtual environment (virtual reality; Study II). The aim was to see if the
      perceptual bias could be detected and also to look at how it would differ in
      these two situations. 90 right-handed subjects (50 young and 40 elderly)
      participated in Study I and 84 subjects (64 young and 20 elderly) participated in
      Study II. Study I showed the rightward bias to be more evident in the elderly
      subjects in both modalities and in more demanding tasks. Study II revealed that
      in the triple task the spatial perceptual bias was evident in both modalities for
      the elderly participants when the conditions were more demanding. An interesting
      finding concerning the right-side perceptual bias was the simultaneous occurrence
      of left-side driving errors, i.e. crossing the lane border to the left especially
      by the elderly. Both of these biases may reflect the asymmetries of the attention
      related neuronal networks.

PMID- 29356012
TI  - Brain, mind and behavior: A tribute to Kenneth Hugdahl.

PMID- 29356013
TI  - Cognitive control in the prefrontal cortex: A central or distributed executive?
AB  - Cognitive control is the foundation for attaining goals by flexible adaptation of
      action to changing environmental demands. It has been hypothesized to be
      critically dependent upon the prefrontal cortex (PFC). In this mini-review,
      evidence for domain-general versus domain-specific cognitive control is examined,
      with a particular focus on attention and memory. The reviewed studies examined
      different levels of cognitive control in relation to performance and patterns of
      brain activity, and a few included direct comparisons of cognitive-control
      modulations across cognitive domains. Within domains, increased demands on
      cognitive control consistently translated into increased PFC activity, but
      limited overlap in recruited PFC regions was observed between domains. It is
      concluded that the PFC supports multiple cognitive-control systems that
      collectively may be conceived of as a distributed executive.

PMID- 29356014
TI  - Impact of carbohydrates on autoinducer-2 secretion of Bifidobacterium longum
      subsp. longum BBMN68.
AB  - : In this study, the regularity of autoinducer-2 (AI-2) secretion during growth
      and the effect of the addition of various carbohydrates on AI-2 secretion in
      Bifidobacterium longum subsp. longum BBMN68 were investigated. The results
      indicated that the AI-2 concentration reached its highest level (2536.60 nmol l-1
      ) at the early stationary growth phase, and then decreased to 1263.72 nmol l-1 at
      the late stationary growth phase in Bifidobacterium cultures. When the density of
      the cultures which mannose, fructose, sucrose and lactose had been added to
      reached an OD600 nm of 1.0, the AI-2 concentrations in the cultures were 1953.84,
      1637.34, 1200.99 and 1077.60 nmol l-1 , respectively. These concentrations were
      all significantly higher than that of the control culture (1031.33 nmol l-1 ).
      Similarly, the addition of fructooligosaccharide significantly increased the AI-2
      concentrations to 2094.29 nmol l-1 . This study provides the advanced evidence
      that certain carbohydrates promote the secretion of AI-2, and that this occurs at
      the single cell level and is therefore unaffected by cell density. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study provided the advanced data of the regularity
      of autoinducer-2 (AI-2) secretion during growth and the promotion on AI-2
      secretion of different added carbohydrates in Bifidobacterium, which may be a new
      potential strategy to improve the acid resistance of Bifidobacterium applied in
      the food industry.

PMID- 29356015
TI  - Acetylcholine receptor antibody-mediated animal models of myasthenia gravis and
      the role of complement.
AB  - Because of the failure of many promising therapeutics identified in preclinical
      evaluation, funding sources have established guidelines for increased rigor in
      animal evaluations. The myasthenia gravis (MG) community of scientists has
      developed guidelines for preclinical assessment for potential MG treatments.
      Here, we provide a focused summary of these recommendations and the role of
      complement in disease development in experimental models of MG.

PMID- 29356016
TI  - Predictors of arrhythmia recurrence in patients with heart failure undergoing
      left atrial ablation for atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) ablation is increasingly used in patients
      with reduced left ventricular ejection fraction (LVEF). The aim of the present
      study was to evaluate the long-term results of a single radiofrequency catheter
      ablation procedure in heart failure (HF) patients with AF. HYPOTHESIS: We tested
      the hypothesis that left atrial ablation is an effective therapeutic modality in
      patients with heart failure. METHODS: Our study included HF patients with LVEF
      <50% who underwent catheter ablation for AF at our department between January
      2010 and March 2017. All patients underwent our institution's protocol for follow
      up post-ablation. RESULTS: The study enrolled a total of 38 patients (mean age,
      54.1 +/- 12.2 years; 28 [73.7%] males; mean LVEF, 38.2% +/- 6.3%). After a mean
      follow-up period of 38.2 months (range, 5-92 months), 28 patients (73.7%) were
      free from arrhythmia recurrence. In multivariate analysis, early arrhythmia
      recurrence (P = 0.03) and amiodarone antiarrhythmic drug administration (P =
      0.003) remained independent predictors of arrhythmia recurrence. CONCLUSIONS: The
      main findings of this study are that (1) a single radiofrequency catheter
      ablation procedure is an effective and safe modality for AF in patients with
      concomitant HF; (2) after a mean 3.3 years of follow-up, 73.7% of HF patients
      remained in sinus rhythm; and (3) early arrhythmia recurrence was a significant
      predictor of arrhythmia recurrence after the blanking period.

PMID- 29356017
TI  - Association between clinical factors and self-underestimation of cardiovascular
      risk in subjects submitted to a routine health evaluation.
AB  - BACKGROUND: The perception of cardiovascular (CV) risk is essential for adoption
      of healthy behaviors. However, subjects underestimate their own risk. HYPOTHESIS:
      Clinical characteristics might be associated with self-underestimation of CV
      risk. METHODS: This is a retrospective, cross-sectional study of individuals
      submitted to routine health evaluation between 2006 and 2012, with calculated
      lifetime risk score (LRS) indicating intermediate or high risk for CV disease
      (CVD). Self-perception of risk was compared with LRS. Logistic regression
      analysis was performed to test the association between clinical characteristics
      and subjective underestimation of CV risk. RESULTS: Data from 5863 subjects (age
      49.4 +/- 7.1 years; 19.9% female) were collected for analysis. The LRS indicated
      an intermediate risk for CVD in 45.7% and a high risk in 54.3% of individuals.
      The self-perception of CV risk was underestimated compared with the LRS in 4918
      (83.9%) subjects. In the adjusted logistic regression model, age (odds ratio
      [OR]: 1.28, 95% confidence interval [CI]: 1.10-1.47 per 10 years, P = 0.001),
      smoking (OR: 1.99, 95% CI: 1.40-2.83, P < 0.001), dyslipidemia (OR: 1.21, 95% CI:
      1.01-1.46, P = 0.045), physical activity (OR: 1.66, 95% CI: 1.36-2.02, P <
      0.001), and use of antihypertensive (OR: 1.49, 95% CI: 1.15-1.92, P = 0.002) and
      lipid-lowering medications (OR: 2.13, 95% CI: 1.56-2.91, P < 0.001) were
      associated with higher chance of risk underestimation, whereas higher body mass
      index (OR: 0.92, 95% CI: 0.90-0.94, P < 0.001), depressive symptoms (OR: 0.46,
      95% CI: 0.37-0.57, P < 0.001), and stress (OR: 0.41, 95% CI: 0.33-0.50, P <
      0.001) decreased the chance. CONCLUSIONS: Among individuals submitted to routine
      medical evaluation, aging, smoking, dyslipidemia, physical activity, and use of
      antihypertensive and lipid-lowering medications were associated with higher
      chance of CV risk underestimation. Subjects with these characteristics may
      benefit from a more careful risk orientation.

PMID- 29356018
TI  - The evolving view of coronary artery calcium and cardiovascular disease risk.
AB  - Calcification of the coronary artery is a complex pathophysiologic process that
      is intimately associated with atherosclerosis. Extensive investigation has
      demonstrated the value of identifying and quantifying coronary artery calcium
      (CAC) in atherosclerotic cardiovascular disease (CVD) prognostication. However,
      over the last several years, an increasing body of evidence has suggested that
      CAC has underappreciated aspects that modulate, and at times attenuate, future
      CVD risk. The most commonly used measure of CAC, the Agatston unit, effectively
      models both higher density and higher area of CAC as risk factors for future CVD
      events. Recent findings from the Multi-Ethnic Study of Atherosclerosis (MESA)
      have challenged this assumption, demonstrating that higher density of CAC is
      protective for coronary heart disease and CVD events. Statins may be associated
      with an increase in CAC, an unexpected finding given their clear benefits in the
      prevention and treatment of CVD. Studies utilizing intracoronary ultrasound and
      coronary computed tomography angiography have demonstrated that calcified
      atherosclerotic plaque-as compared with noncalcified or sparsely calcified plaque
      is associated with fewer CVD events. These studies lend support to the often
      asserted (but as yet unvalidated) view that calcification may play a role in
      plaque stabilization. Furthermore, vascular calcification, though a surrogate for
      atherosclerotic plaque burden, may also possess identifiable aspects that can
      refine CVD risk assessment.

PMID- 29356019
TI  - Time-resolved fluorescence (TRF) and diffuse reflectance spectroscopy (DRS) for
      margin analysis in breast cancer.
AB  - PURPOSE: One of the major problems in breast cancer surgery is defining surgical
      margins and establishing complete tumor excision within a single surgical
      procedure. The goal of this work is to establish instrumentation that can
      differentiate between tumor and normal breast tissue with the potential to be
      implemented in vivo during a surgical procedure. METHODS: A time-resolved
      fluorescence and reflectance spectroscopy (tr-FRS) system is used to measure
      fluorescence intensity and lifetime as well as collect diffuse reflectance (DR)
      of breast tissue, which can subsequently be used to extract optical properties
      (absorption and reduced scatter coefficient) of the tissue. The tr-FRS data
      obtained from patients with Invasive Ductal Carcinoma (IDC) whom have undergone
      lumpectomy and mastectomy surgeries is presented. A preliminary study was
      conducted to determine the validity of using banked pre-frozen breast tissue
      samples to study the fluorescence response and optical properties. Once the
      validity was established, the tr-FRS system was used on a data-set of 40 pre
      frozen matched pair cases to differentiate between tumor and normal breast
      tissue. All measurements have been conducted on excised normal and tumor breast
      samples post surgery. RESULTS: Our results showed the process of freezing and
      thawing did not cause any significant differences between fresh and pre-frozen
      normal or tumor breast tissue. The tr-FRS optical data obtained from 40 banked
      matched pairs showed significant differences between normal and tumor breast
      tissue. CONCLUSION: The work detailed in the main study showed the tr-FRS system
      has the potential to differentiate malignant from normal breast tissue in women
      undergoing surgery for known invasive ductal carcinoma. With further work, this
      successful outcome may result in the development of an accurate intraoperative
      real-time margin assessment system. Lasers Surg. Med. 50:236-245, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29356020
TI  - Matrine inhibits the progression of prostate cancer by promoting expression of
      GADD45B.
AB  - BACKGROUND: Matrine is a naturally occurring alkaloid extracted from the Chinese
      herb Sophora flavescens. It has been demonstrated to exhibit antiproliferative
      properties, promote apoptosis, and inhibit cell invasion in a number of cancer
      cell lines by modulating the NF-kappaB pathway to downregulate the expression of
      MMP2 and MM9. It has also been shown to improve the efficacy of chemotherapy when
      it is combined with other chemotherapy drugs. However, the therapeutic potential
      of matrine for prostate cancer needs to be further studied. METHODS: We analyzed
      KEGG pathways of differential gene expression between matrine-treated and
      untreated prostate cancer cell lines and identified GADD45B as one of major
      target genes of matrine based on its role in apoptosis and prognosis value for
      prostate cancer patients in TCGA database. We further analyzed the expression of
      GADD45B protein in a tissue microarray and mRNA in TCGA database, and tested the
      synergistic impacts of matrine and GADD45B overexpression on proliferation,
      apoptosis, migration and invasion of prostate cancer cell DU145. RESULTS: Matrine
      promoted the expression of GADD45B, a tumor suppressive gene that is involved in
      the regulation of cell cycle, DNA damage repair, cell survival, aging, apoptosis
      and other cellular processes through p38/JNK, ROS-GADD45B-p38, or other signal
      pathways. Although GADD45B is elevated in prostate cancer tissues, levels of
      GADD45B in prostate tumor tissues are reduced at late stage of tumor invasion,
      and higher levels of GADD45B predict better survivals of prostate cancer
      patients. CONCLUSIONS: Matrine may be used to treat prostate cancer patients to
      increase the levels of GADD45B to inhibit tumor invasion and improve patient
      survivals.

PMID- 29356021
TI  - Evaluation of fidaxomicin usage patterns and outcomes for Clostridium difficile
      infection across the United States Veterans Health Administration.
AB  - WHAT IS KNOWN AND OBJECTIVE: Fidaxomicin was recently approved for the treatment
      of Clostridium difficile infection (CDI). Limited data on its use exist outside
      of the phase 3 trials. The purposes of this study were to assess the compliance
      with the Veterans Health Administration (VHA) fidaxomicin criteria for use and
      describe patient characteristics and outcomes following fidaxomicin treatment for
      CDI using real-world data within the VHA system. METHODS: This was a multicentre,
      retrospective, observational study including all adult patients who received at
      least 1 dose of fidaxomicin at any Veterans Affairs Medical Center. RESULTS AND
      DISCUSSION: A total of 880 unique patients received 1098 courses of fidaxomicin,
      resulting in an overall usage rate per C. difficile-positive laboratory test of
      1.98%. The rate of fidaxomicin courses per 1000 C. difficile-positive diagnostic
      tests increased steadily from 2011 through 2015 and plateaued from 2015 to 2016.
      Compliance with the VHA criteria for use was low (9.1%). The majority of courses
      were given for a first recurrence (25.0%), followed by an initial episode (23.9%)
      of CDI. The failure and recurrence rates were 6.8% and 24.4%, respectively. WHAT
      IS NEW AND CONCLUSION: Although overall use of fidaxomicin was low, compliance
      with the VHA criteria for use was also low, suggesting that the criteria may need
      to be revised. Further studies are warranted to clarify the role of fidaxomicin
      in clinical practice.

PMID- 29356022
TI  - Optical treatment of amblyopia in older children and adults is essential prior to
      enrolment in a clinical trial.
AB  - PURPOSE: Optical treatment alone can improve visual acuity (VA) in children with
      amblyopia, thus clinical trials investigating additional amblyopia therapies
      (such as patching or videogames) for children require a preceding optical
      treatment phase. Emerging therapies for adult patients are entering clinical
      trials. It is unknown whether optical treatment is effective for adults with
      amblyopia and whether an optical correction phase is required for trials
      involving adults. METHODS: We examined participants who underwent optical
      treatment in the Binocular Treatment for Amblyopia using Videogames (BRAVO)
      clinical trial (ANZCTR ID: ACTRN12613001004752). Participants were recruited in
      three age groups (7 to 12, 13 to 17, or >=18 years), and had unilateral amblyopia
      due to anisometropia and/or strabismus, with amblyopic eye VA of 0.30-1.00 logMAR
      (6/12 to 6/60, 20/40 to 20/200). Corrective lenses were prescribed based on
      cycloplegic refraction to fully correct any anisometropia. VA was assessed using
      the electronic visual acuity testing algorithm (e-ETDRS) test and near
      stereoacuity was assessed using the Randot Preschool Test. Participants were
      assessed every four weeks up to 16 weeks, until either VA was stable or until
      amblyopic eye VA improved to better than 0.30 logMAR, rendering the participant
      ineligible for the trial. RESULTS: Eighty participants (mean age 24.6 years,
      range 7.6-55.5 years) completed four to 16 weeks of optical treatment. A small
      but statistically significant mean improvement in amblyopic eye VA of 0.05 logMAR
      was observed (S.D. 0.08 logMAR; paired t-test p < 0.0001). Twenty-five
      participants (31%) improved by >=1 logMAR line and of these, seven (9%) improved
      by >=2 logMAR lines. Stereoacuity improved in 15 participants (19%). Visual
      improvements were not associated with age, presence of strabismus, or prior
      occlusion treatment. Two adult participants withdrew due to intolerance to
      anisometropic correction. Sixteen out of 80 participants (20%) achieved better
      than 0.30 logMAR VA in the amblyopic eye after optical treatment. Nine of these
      participants attended additional follow-up and four (44%) showed further VA
      improvements. CONCLUSIONS: Improvements from optical treatment resulted in one
      fifth of participants becoming ineligible for the main clinical trial. Studies
      investigating additional amblyopia therapies must include an appropriate optical
      treatment only phase and/or parallel treatment group regardless of patient age.
      Optical treatment of amblyopia in adult patients warrants further investigation.

PMID- 29356023
TI  - Biochemical evaluation of male androgen status: Beyond total testosterone.

PMID- 29356024
TI  - Reply.

PMID- 29356025
TI  - Identification and therapeutic intervention of coactivated anaplastic lymphoma
      kinase, fibroblast growth factor receptor 2, and ephrin type-A receptor 5 kinases
      in hepatocellular carcinoma.
AB  - : Though kinase inhibitors have been heavily investigated in the clinic to combat
      advanced hepatocellular carcinoma (HCC), clinical outcomes have been
      disappointing overall, which may be due to the absence of kinase-addicted subsets
      in HCC patients. Recently, strategies that simultaneously inhibit multiple
      kinases are increasingly appreciated in HCC treatment, yet they are challenged by
      the dynamic nature of the kinase networks. This study aims to identify clustered
      kinases that may cooperate to drive the malignant growth of HCC. We show that
      anaplastic lymphoma kinase, fibroblast growth factor receptor 2, and ephrin type
      A receptor 5 are the essential kinases that assemble into a functional cluster to
      sustain the viability of HCC cells through downstream protein kinase B-dependent,
      extracellular signal-regulated kinase-dependent, and p38-dependent signaling
      pathways. Their coactivation is associated with poor prognosis for overall
      survival in about 13% of HCC patients. Moreover, their activities are tightly
      regulated by heat shock protein 90 (Hsp90). Thereby Combined kinase inhibition or
      targeting of heat shock protein 90 led to significant therapeutic responses both
      in vitro and in vivo. CONCLUSION: Our findings established a paradigm that
      highlights the cooperation of anaplastic lymphoma kinase, fibroblast growth
      factor receptor 2, and ephrin type-A receptor 5 kinases in governing the growth
      advantage of HCC cells, which might offer a conceptual "combined therapeutic
      target" for diagnosis and subsequent intervention in a subgroup of HCC patients.
      (Hepatology 2018).

PMID- 29356026
TI  - Light-emitting diodes in dermatology: A systematic review of randomized
      controlled trials.
AB  - OBJECTIVE: In dermatology, patient and physician adoption of light-emitting diode
      (LED) medical technology continues to grow as research indicates that LEDs may be
      used to treat skin conditions. The goal of this systematic review is to
      critically analyze published randomized controlled trials (RCTs) and provide
      evidence-based recommendations on the therapeutic uses of LEDs in dermatology
      based on published efficacy and safety data. METHODS: A systematic review of the
      published literature on the use of LED treatments for skin conditions was
      performed on September 13th 2017. RESULTS: Thirty-one original RCTs were suitable
      for review. CONCLUSIONS: LEDs represent an emerging modality to alter skin
      biology and change the paradigm of managing skin conditions. Acne vulgaris,
      herpes simplex and zoster, and acute wound healing received grade of
      recommendation B. Other skin conditions received grade of recommendation C or D.
      Limitations of some studies include small patient sample sizes (n < 20), absent
      blinding, no sham placebo, and varied treatment parameters. Due to few incidences
      of adverse events, affordability, and encouraging clinical results, we recommend
      that physicians use LEDs in clinical practice and researchers continue to explore
      the use of LEDs to treat skin conditions. Lasers Surg. Med. 9999:1-16, 2018. (c)
      2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals,
      Inc.

PMID- 29356027
TI  - Young children's preference for solitary play: Implications for socio-emotional
      and school adjustment.
AB  - The purpose of this study was to provide additional psychometric support for the
      Preference for Solitary Play Interview (PSPI) and to examine the associations
      between self-reported preference for solitary play and indices of adjustment in
      early childhood. Participants were N = 340 children attending kindergarten and
      grade 1. Children completed the PSPI, and teachers provided assessments of
      children's socio-emotional and school adjustment. In support of the validity of
      the PSPI, preference for solitary play was positively associated with asocial
      behaviours. Further, preference for solitary play displayed an indirect (but not
      direct) association with peer exclusion via asocial behaviours. Findings are
      discussed in terms of the social and behavioural implications of preference for
      solitary play in early childhood. Statement of contribution What is already known
      on this subject? Children who spend more time alone are at increased risk of
      adjustment difficulties. However, some individuals desire to spend time alone
      because of an appreciation for solitude. A preference for solitude is not
      associated with negative adjustment in adults and older youth. What does this
      study add? This study is among the first to examine self-reported preference for
      solitary in early childhood. Preference for solitude may not be related to
      emotional or school difficulties in young children. However, a heightened display
      of solitary behaviours may still evoke negative responses from peers.

PMID- 29356028
TI  - Deep learning for segmentation of brain tumors: Impact of cross-institutional
      training and testing.
AB  - BACKGROUND AND PURPOSE: Convolutional neural networks (CNNs) are commonly used
      for segmentation of brain tumors. In this work, we assess the effect of cross
      institutional training on the performance of CNNs. METHODS: We selected 44
      glioblastoma (GBM) patients from two institutions in The Cancer Imaging Archive
      dataset. The images were manually annotated by outlining each tumor component to
      form ground truth. To automatically segment the tumors in each patient, we
      trained three CNNs: (a) one using data for patients from the same institution as
      the test data, (b) one using data for the patients from the other institution and
      (c) one using data for the patients from both of the institutions. The
      performance of the trained models was evaluated using Dice similarity
      coefficients as well as Average Hausdorff Distance between the ground truth and
      automatic segmentations. The 10-fold cross-validation scheme was used to compare
      the performance of different approaches. RESULTS: Performance of the model
      significantly decreased (P < 0.0001) when it was trained on data from a different
      institution (dice coefficients: 0.68 +/- 0.19 and 0.59 +/- 0.19) as compared to
      training with data from the same institution (dice coefficients: 0.72 +/- 0.17
      and 0.76 +/- 0.12). This trend persisted for segmentation of the entire tumor as
      well as its individual components. CONCLUSIONS: There is a very strong effect of
      selecting data for training on performance of CNNs in a multi-institutional
      setting. Determination of the reasons behind this effect requires additional
      comprehensive investigation.

PMID- 29356029
TI  - Passive transfer models of myasthenia gravis with muscle-specific kinase
      antibodies.
AB  - Myasthenia gravis (MG) with antibodies to muscle-specific kinase (MuSK) is
      characterized by fluctuating fatigable weakness. In MuSK MG, involvement of
      bulbar muscles, neck, and shoulder and respiratory weakness are more prominent
      than in acetylcholine receptor (AChR) MG. MuSK autoantibodies are mainly of the
      IgG4 subclass, and as such are unable to activate complement, have low affinity
      for Fc receptors, and are functionally monovalent. Therefore, the pathogenicity
      of IgG4 MuSK autoantibodies was initially questioned. A broad collection of in
      vitro active immunization and passive transfer models has been developed that
      have shed light on the pathogenicity of MuSK autoantibodies. Passive transfer
      studies with purified IgG4 from MuSK MG patients confirmed that IgG4 is
      sufficient to reproduce clear clinical, electrophysiological, and histological
      signs of myasthenia. In vitro experiments revealed that MuSK IgG4 autoantibodies
      preferably bind the first Ig-like domain of MuSK, correlate with disease
      severity, and interfere with the association between MuSK and low-density
      lipoprotein receptor-related protein 4 and collagen Q. Some patients have
      additional IgG1 MuSK autoantibodies, but their role in the disease is unclear.
      Altogether, this provides a rationale for epitope-specific or IgG4-specific
      treatment strategies for MuSK MG and emphasizes the importance of the development
      of different experimental models.

PMID- 29356030
TI  - Protein in the Hospital: Gaining Perspective and Moving Forward.
AB  - Provision of adequate protein is crucial for optimizing outcomes in hospitalized
      patients. However, the methodologies upon which current recommendations are based
      have limitations, and little is known about true requirements in any clinical
      population. In this tutorial, we aim to give clinicians an understanding of how
      current protein recommendations were developed, an appreciation for the
      limitations of these recommendations, and an overview of more sophisticated
      approaches that can be applied to better define protein requirements. A broader
      perspective of the challenges and opportunities in determining clinical protein
      requirements can help clinicians think critically about the individualized
      nutrition care they provide to their patients with the goal of administering
      adequate protein to optimize outcomes.

PMID- 29356031
TI  - Are immunoglobulins against the HBsAg still needed in liver transplantation for
      hepatitis D?

PMID- 29356033
TI  - Gold nanospheres enhanced photothermal therapy in a rat model.
AB  - BACKGROUND AND OBJECTIVE: Efficient photothermal conversion of gold nanoparticles
      with strong light absorption suggests their wide use as selective photothermal
      agents in biomedical fields. The aim of this study is to investigate the use of
      gold nanospheres (GNPs) as exogenous visible light absorbers to improve laser
      treatment of port-wine stains. MATERIALS AND METHODS: Thiol-terminated
      methoxypolyethylene glycol modified GNPs (PEG-GNPs) with peak extinction matching
      the visible light wavelength of the laser being used were synthesized. An in
      vitro capillary experiment was prepared to investigate the thermal response of
      blood vessels with and without injection of 4.54 mg PEG-GNPs in mice prior to
      irradiation by a frequency-doubled Nd:YAG laser at a wavelength of 532 nm.
      RESULTS: The in vitro results demonstrated that the photocoagulation size in
      blood vessels after exposed to laser light increased with the increment of
      concentration of PEG-GNPs in blood within a certain range. However, the unwanted
      thermal response (i.e., cavitation) occurred when the concentration of PEG-GNPs
      in blood was larger than 2.5 mg/ml. The in vivo results suggested that more
      obvious blood thermal response can be induced by laser light after injection of
      PEG-GNPs. After injection of 4.54 mg PEG-GNPs, laser radiant exposure required
      for thread-like constriction of blood vessels decreased from 12.5 to 9.8 J/cm2
      with the pulse duration of 10 ms, from 15 to 11.85 J/cm2 with the pulse duration
      of 30 ms, respectively. CONCLUSION: This in vitro and in vivo experimental
      results show that PEG-GNPs combined with laser light could be a promising
      modality to reduce the radiant exposure required for obvious blood thermal
      response, thereby providing a potential strategy for improving the laser
      treatment of cutaneous vascular lesions. Lasers Surg. Med. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29356034
TI  - Rare germline mutations in African American men diagnosed with early-onset
      prostate cancer.
AB  - BACKGROUND: African Americans have both a higher incidence of prostate cancer and
      greater disease-specific mortality compared with non-Hispanic whites.
      Historically, the investigation of the contribution of rare genetic variants to
      prostate cancer in African American men has been hampered by low participation in
      large genetic studies, particularly those focused on early-onset and familial
      disease. METHODS: We sequenced 160 genes purported to be involved in carcinogenic
      pathways in germline DNA samples collected from 96 African American men diagnosed
      with early-onset prostate cancer (<=55 years at diagnosis). REVEL software was
      used to determine the pathogenic potential of observed missense variants.
      RESULTS: We observed three protein-truncating mutations, one in BRCA2 and two in
      BRIP1 in three African American men diagnosed with early-onset prostate cancer.
      Furthermore, we observed five rare, mostly private, missense variants among four
      genes (BRCA1, BRCA2, PMS2, and ATM) that were predicted to be deleterious and
      hence likely pathogenic in our patient sample. CONCLUSIONS: Protein-truncating
      mutations in BRCA2 and BRIP1 were discovered in African American men diagnosed
      with early-onset prostate cancer. Further study is necessary to determine the
      role of rare, missense variants to prostate cancer incidence, and progression in
      this group of high-risk men.

PMID- 29356032
TI  - Noninvasive, Quantitative Assessment of Liver Fat by MRI-PDFF as an Endpoint in
      NASH Trials.
AB  - Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of
      chronic liver disease worldwide, and the progressive form of this condition,
      nonalcoholic steatohepatitis (NASH), has become one of the leading indications
      for liver transplantation. Despite intensive investigations, there are currently
      no United States Food and Drug Administration-approved therapies for treating
      NASH. A major barrier for drug development in NASH is that treatment response
      assessment continues to require liver biopsy, which is invasive and interpreted
      subjectively. Therefore, there is a major unmet need for developing noninvasive,
      objective, and quantitative biomarkers for diagnosis and assessment of treatment
      response. Emerging data support the use of magnetic resonance imaging-derived
      proton density fat fraction (MRI-PDFF) as a noninvasive, quantitative, and
      accurate measure of liver fat content to assess treatment response in early-phase
      NASH trials. In this review, we discuss the role and utility, including potential
      sample size reduction, of MRI-PDFF as a quantitative and noninvasive imaging
      based biomarker in early-phase NASH trials. Nonalcoholic fatty liver disease
      (NAFLD) is currently the most common cause of chronic liver disease worldwide.()
      NAFLD can be broadly classified into two categories: nonalcoholic fatty liver,
      which has a minimal risk of progression to cirrhosis, and nonalcoholic
      steatohepatitis (NASH), the more progressive form of NAFLD, which has a
      significantly increased risk of progression to cirrhosis.() Over the past two
      decades, NASH-related cirrhosis has become the second leading indication for
      liver transplantation in the United States.() For these reasons, pharmacological
      therapy for NASH is needed urgently. Despite intensive investigations, there are
      currently no therapies for treating NASH that have been approved by the United
      States Food and Drug Administration.().

PMID- 29356035
TI  - An interesting case of systemic lupus erythematosus in a patient with Moebius
      syndrome.
AB  - Moebius' syndrome (MS) is characterized by a nonprogressive facial palsy
      associated with impairment in eye abduction, which can be uni- or bilateral. Some
      authors raise the possibility that patients with MS may suffer from social
      stigmatism due to their facial dysmorphism and that constant teasing and bullying
      perpetrated by people in the same social circle are adjuvants in the development
      of low self-esteem, behavioral problems, and even psychiatric disorders.
      Psychological stress, anxiety, and depression are factors contributing to both
      development and impairment of autoimmune diseases, such as systemic lupus
      erythematosus (SLE). The objective of this work is to report the case of a
      patient with MS who developed SLE. In the present case report, we have emphasized
      the importance of both clinical dental examination and surgeon-dentist in the
      early diagnosis of systemic diseases by considering that these conditions can
      affect both syndromic and normoreactive patients.

PMID- 29356036
TI  - DNAH6 is a novel candidate gene associated with sperm head anomaly.
AB  - Globozoospermia and acephalic spermatozoa are two rare sperm head anomalies
      associated with male infertility. Combination of the two phenotypes in the same
      patient is extremely rare, so the underlying pathogenesis of this disorder
      remains unclear. Here, we report a 35-year-old infertile male, who presented with
      30% of sperm-lacked heads and 69% of sperm round-headed or small-headed with neck
      thickening in his ejaculate. Subsequent whole-exome sequencing (WES) analysis
      identified compound heterozygous variants within the DNAH6 gene. DNAH6 is a
      testis-specific-expressed protein that was localised to the neck region in the
      spermatozoa of normal control; however, immunofluorescent staining failed to
      detect DNAH6 protein in the patient's spermatozoa. Quantitative real-time PCR
      analysis also showed the complete absence of DNAH6 mRNA in the patient's
      spermatozoa. Moreover, two cycles of in vitro fertilisation (IVF)-assisted
      reproduction were carried out, but pregnancy was not achieved after embryo
      transfer. Therefore, rare sequence variants in DNAH6 might be susceptibility
      risks for human sperm head anomaly.

PMID- 29356037
TI  - Placental growth factor: New treatment target bringing hope for hepatopulmonary
      syndrome.

PMID- 29356038
TI  - EXTENSOR DIGITORUM BREVIS INNERVATED BY THE TIBIAL NERVE ("ALL TIBIAL FOOT"):
      ANOMALOUS INNERVATION OR TECHNICAL PITFALL? (A REPLY).

PMID- 29356039
TI  - EXTENSOR DIGITORUM BREVIS INNERVATED BY THE TIBIAL NERVE ("ALL TIBIAL FOOT"):
      ANOMALOUS INNERVATION OR TECHNICAL PITFALL? (A REPLY).

PMID- 29356040
TI  - Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination
      and degradation in hepatocellular carcinoma progress.
AB  - : Hepatocytes are epithelial cells with highly specialized polarity. The disorder
      and loss of hepatocyte polarity leads to a weakness of cell adhesion and
      connection, the induction of epithelial-mesenchymal transition, and eventually
      the occurrence of hepatocellular carcinoma (HCC). Cluster of differentiation 147
      (CD147), a tumor-related glycoprotein, promotes epithelial-mesenchymal transition
      and the invasion of HCC. However, the function of CD147 in hepatocyte
      depolarization is unknown. Here we identified that CD147 was basolaterally
      polarized in hepatocyte membrane of liver tissues and HepG2 cells. CD147 not only
      promoted transforming growth factor-beta1-mediated hepatocyte polarity loss but
      also directly induced endocytosis and down-regulation of E-cadherin which
      contributed to hepatocyte depolarization. Overexpression of CD147 induced Src
      activation and subsequently recruited ubiquitin ligase Hakai for E-cadherin
      ubiquitination and lysosomal degradation, leading to decreases of partitioning
      defective 3 expression and beta-catenin nuclear translocation. This signal
      transduction was initiated by competitive binding of CD147 with integrin beta1
      that interrupted the interaction between the Arg-Gly-Asp motif of fibronectin and
      integrin beta1. The specific antibodies targeting integrin alpha5 and beta1
      reversed the decrease of E-cadherin and partitioning defective 3 levels induced
      by CD147 overexpression. In human liver tissues, CD147 polarity rates
      significantly declined from liver cirrhosis (71.4%) to HCC (10.4%). CD147
      polarized localization negatively correlated with Child-Pugh scores in human
      liver cirrhosis (r = -0.6092, P < 0.0001) and positively correlated with
      differentiation grades in HCC (r = 0.2060, P = 0.004). HCC patients with CD147
      polarized localization had significantly better overall survival than patients
      with CD147 nonpolarity (P = 0.021). CONCLUSION: The ectopic CD147-polarized
      distribution on basolateral membrane promotes hepatocyte depolarization by
      activation of the CD147-integrin alpha5beta1-E-cadherin ubiquitination
      partitioning defective 3 decrease and beta-catenin translocation signaling
      cascade, replenishing a molecular pathway in hepatic carcinogenesis. (Hepatology
      2018;68:317-332).

PMID- 29356041
TI  - Cryptic Emotions and the Emergence of a Metatheory of Mind in Popular Filmmaking.
AB  - Hollywood movies can be deeply engaging and easy to understand. To succeed in
      this manner, feature-length movies employ many editing techniques with strong
      psychological underpinnings. We explore the origins and development of one of
      these, the reaction shot. This shot typically shows a single, unspeaking
      character with modest facial expression in response to an event or to the
      behavior or speech of another character. In a sample of movies from 1940 to 2010,
      we show that the prevalence of one type of these shots-which we call the cryptic
      reaction shot-has grown dramatically. These shots are designed to enhance
      viewers' emotional involvement with characters. They depict a facial gesture that
      reflects a slightly negative and slightly aroused emotional state. Their use at
      the end of conversations, and typically at the end of scenes, helps to leave
      viewers in a state of speculation about what the character is thinking and what
      her thoughts may mean for the ongoing narrative.

PMID- 29356042
TI  - Does antiplatelet therapy really reduce the risk of hepatocellular carcinoma in
      hepatitis B patients with antiviral drugs?

PMID- 29356043
TI  - A Noncovalent Binding Strategy to Capture Noble Gases, Hydrogen and Nitrogen.
AB  - A molecular design strategy to develop receptor systems for the entrapment of
      noble gases, H2 and N2 is described using M06L-D3/6-311++G(d,p)//M06L/6
      311++G(d,p) DFT method. These receptors made with two-, three-, four- and five
      fluorinated benzene cores, linked with methelene units viz. RI , RII , RIII and
      RIV as well as the corresponding non-fluorinated hydrocarbons viz. RIH , RIIH ,
      RIIIH and RIVH show a steady and significant increase in binding energy (Eint )
      with increase in the number of aromatic rings in the receptor. A stabilizing
      "cage effect" is observed in the cyclophane type receptors RIV and RIVH which is
      26-48% of total Eint for all except the larger sized Kr, Xe and N2 complexes.
      Eint of RIV ...He, RIV ...Ne, RIV ...Ar, RIV ...Kr, RIV ...H2 and RIV ...N2 is
      4.89, 7.03, 6.49, 6.19, 8.57 and 8.17 kcal/mol, respectively which is 5- to9-fold
      higher than that of hexafluorobenzene. Similarly, compared to benzene, multiple
      fold increase in Eint is observed for RIVH receptors with noble gases, H2 and N2
      . Fluorination of the aromatic core has no significant impact on Eint (~ +/-0.5
      kcal/mol) for most of the systems with a notable exception of the cage receptor
      RIV for N2 where fluorination improves Eint by 1.61 kcal/mol. The Eint of the
      cage receptors may be projected as one of the highest interaction energy ranges
      reported for noble gases, H2 and N2 for a neutral carbon framework. Synthesis of
      such systems is promising in the study of molecules in confined environment. (c)
      2018 Wiley Periodicals, Inc.

PMID- 29356045
TI  - Death and the Self.
AB  - It is an old philosophical idea that if the future self is literally different
      from the current self, one should be less concerned with the death of the future
      self (Parfit, ). This paper examines the relation between attitudes about death
      and the self among Hindus, Westerners, and three Buddhist populations (Lay
      Tibetan, Lay Bhutanese, and monastic Tibetans). Compared with other groups,
      monastic Tibetans gave particularly strong denials of the continuity of self,
      across several measures. We predicted that the denial of self would be associated
      with a lower fear of death and greater generosity toward others. To our surprise,
      we found the opposite. Monastic Tibetan Buddhists showed significantly greater
      fear of death than any other group. The monastics were also less generous than
      any other group about the prospect of giving up a slightly longer life in order
      to extend the life of another.

PMID- 29356044
TI  - Expression analysis of HMGB1 in histological samples of malignant pleural
      mesothelioma.
AB  - AIMS: High mobility group box 1 (HMGB1) is a chromatin structural protein,
      expressed ubiquitously in the nuclei of mammalian cells. When transported
      extracellularly, it acts as a tumour suppressor and oncogenic protein. In
      malignant pleural mesothelioma (MPM), high serum levels of HMGB1 have been
      related to a poor prognosis. Conversely, the significance of HMGB1 expression in
      MPM tissues is still unclear. METHODS AND RESULTS: Biopsy samples from 170
      patients with MPM were assessed by immunohistochemistry and reverse transcription
      polymerase chain reaction (RT-PCR) to evaluate HMGB1 protein and gene expression.
      The expression level of HMGB1 protein was scored using a semiquantitative system
      that sums the intensity (0-3) and the percentage (from 0 to 4) of positively
      stained cells in nuclei, cytoplasm and in both. The final score was considered as
      high (>3) or low (<3) expression. Gene expression levels were calculated using
      the DeltaDeltaCt method. High expression levels of HMGB1 as total (P = 0.0011)
      and cytoplasmic score (P = 0.0462) were related to a worse disease-specific
      survival (DSS) in the entire cohort and in the clinicopathological subgroups. No
      significant correlation was found between HMGB1 gene expression and DSS.
      CONCLUSIONS: These findings indicate that HMGB1 may be a useful prognostic
      biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also
      expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a
      diagnostic biomarker in histological samples of mesothelioma.

PMID- 29356048
TI  - Editorial.

PMID- 29356046
TI  - A Large-Scale Analysis of Variance in Written Language.
AB  - The collection of very large text sources has revolutionized the study of natural
      language, leading to the development of several models of language learning and
      distributional semantics that extract sophisticated semantic representations of
      words based on the statistical redundancies contained within natural language
      (e.g., Griffiths, Steyvers, & Tenenbaum, ; Jones & Mewhort, ; Landauer & Dumais,
      ; Mikolov, Sutskever, Chen, Corrado, & Dean, ). The models treat knowledge as an
      interaction of processing mechanisms and the structure of language experience.
      But language experience is often treated agnostically. We report a distributional
      semantic analysis that shows written language in fiction books varies appreciably
      between books from the different genres, books from the same genre, and even
      books written by the same author. Given that current theories assume that word
      knowledge reflects an interaction between processing mechanisms and the language
      environment, the analysis shows the need for the field to engage in a more
      deliberate consideration and curation of the corpora used in computational
      studies of natural language processing.

PMID- 29356050
TI  - Partially linearized external models to active-space coupled-cluster through
      connected hextuple excitations.
AB  - Partially linearized external models to active-space coupled-cluster through
      hextuple excitations, for example, CC{SDtqph}L , CCSD{tqph}L , and CCSD{tqph}hyb,
      are implemented and compared with the full active-space CCSDtqph. The
      computational scaling of CCSDtqph coincides with that for the standard coupled
      cluster singles and doubles (CCSD), yet with a much large prefactor. The
      approximate schemes to linearize the external excitations higher than doubles are
      significantly cheaper than the full CCSDtqph model. These models are applied to
      investigate the bond dissociation energies of diatomic molecules (HF, F2 , CuH,
      and CuF), and the potential energy surfaces of the bond dissociation processes of
      HF, CuH, H2 O, and C2 H4 . Among the approximate models, CCSD{tqph}hyb provides
      very accurate descriptions compared with CCSDtqph for all of the tested systems.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 29356052
TI  - Increased risk of psoriasis following scabies infection: A nationwide population
      based matched-cohort study.
AB  - Both scabies and psoriasis are pruritic inflammatory skin diseases. The clinical
      manifestations are similar and provocation of psoriasis by mite bite was
      reported. The association between scabies and psoriasis was not investigated
      before. We conducted this nationwide population-based matched-cohort study to
      describe if patients with a diagnosis of scabies have a different risk of
      developing new psoriasis. From the National Health Insurance Research Database of
      Taiwan, patients with scabies (n = 5137) were identified and matched for age and
      sex with non-scabies controls (n = 19 142). We tracked them for a 7-year period
      to identify the incidence of psoriasis. One hundred and ninety (0.8%) patients
      with newly diagnosed psoriasis were identified; 91 (1.8%) from the scabies group
      and 99 (0.5%) from the control group. Patients with scabies had a higher risk of
      subsequent psoriasis, with a crude hazard ratio of 3.45 and an adjusted hazard
      ratio (aHR) of 3.03 (95% confidence interval, 2.24-4.11). An increased risk for
      psoriasis among patients with scabies was observed (aHR, 3.03). Immunopathology
      involving the T-helper 17 cell-mediated inflammatory pathway may contribute to
      this association. Physicians may consider implementing assessments of psoriatic
      symptoms in patients with scabies.

PMID- 29356053
TI  - Effects of age and diet on glucose and insulin dynamics in the horse.
AB  - BACKGROUND: Age and diet may affect insulin sensitivity (SI) but these factors
      have received limited investigation in horses. OBJECTIVES: To measure minimal
      model parameters during an insulin-modified frequently sampled intravenous
      glucose tolerance test (FSIGTT) after adaptation to a forage only diet (HAY) or
      forage supplemented with either starch/sugar-rich (SS) or oil/fibre-rich (FF)
      concentrate feeds; and to assess glucose and insulin responses to a standardised
      meal challenge (SMC, 4 g/kg BW of SS) after diet adaptation in adult and aged
      mares. STUDY DESIGN: Latin square design with eight adult (5-12 years) and nine
      aged (>19 years) healthy mares. METHODS: Diets were fed for 6 weeks, and the
      FSIGTT and SMC were performed after 31-32 and 41 days on each diet respectively.
      Data were analysed by a mixed ANOVA for repeated measures. RESULTS: Acute insulin
      response to glucose (AIRg) was greater and SI was lower in aged horses, compared
      with adults, regardless of diet. Both AIRg and SI were greater in aged mares
      after adaptation to SS, as compared with HAY. Similar trends, although not
      statistically significant, were observed after adaptation to SS in adult mares.
      Peak insulin concentration and area under the insulin vs. time curve during the
      SMC were greater in aged than adult mares with all diets. Furthermore, area under
      the glucose vs. time curve was lower after adaptation to SS, when compared with
      other diets, in both groups. MAIN LIMITATIONS: Transient weight loss occurred at
      the beginning of the study and only one sex was included. Incomplete ingestion of
      the SMC by four mares was another limitation. CONCLUSIONS: Insulin responses to
      i.v. and enteral nonstructural carbohydrate challenge increase with age in
      healthy horses, regardless of diet fed.

PMID- 29356051
TI  - Optical coherence tomography angiography of normal skin and inflammatory
      dermatologic conditions.
AB  - BACKGROUND: In clinical dermatology, the identification of subsurface vascular
      and structural features known to be associated with numerous cutaneous
      pathologies remains challenging without the use of invasive diagnostic tools.
      OBJECTIVE: To present an advanced optical coherence tomography angiography (OCTA)
      method to directly visualize capillary-level vascular and structural features
      within skin in vivo. METHODS: An advanced OCTA system with a 1310 nm wavelength
      was used to image the microvascular and structural features of various skin
      conditions. Subjects were enrolled and OCTA imaging was performed with a field of
      view of approximately 10 * 10 mm. Skin blood flow was identified using an optical
      microangiography (OMAG) algorithm. Depth-resolved microvascular networks and
      structural features were derived from segmented volume scans, representing tissue
      slabs of 0-132, 132-330, and 330-924 MUm, measured from the surface of the skin.
      RESULTS: Subjects with both healthy and pathological conditions, such as benign
      skin lesions, psoriasis, chronic graft-versus-host-disease (cGvHD), and
      scleroderma, were OCTA scanned. Our OCTA results detailed variations in
      vascularization and local anatomical characteristics, for example, depth
      dependent vascular, and structural alterations in psoriatic skin, alongside their
      resolve over time; vascular density changes and distribution irregularities,
      together with corresponding structural depositions in the skin of cGvHD patients;
      and vascular abnormalities in the nail folds of a patient with scleroderma.
      CONCLUSION: OCTA can image capillary blood flow and structural features within
      skin in vivo, which has the potential to provide new insights into the
      pathophysiology, as well as dynamic changes of skin diseases, valuable for
      diagnoses, and non-invasive monitoring of disease progression and treatment.
      Lasers Surg. Med. 50:183-193, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29356054
TI  - Japanese case of xeroderma pigmentosum complementation group C with a novel
      mutation.

PMID- 29356055
TI  - Abnormal locomotor muscle recruitment activity is present in horses with
      shivering and Purkinje cell distal axonopathy.
AB  - BACKGROUND: Cerebellar Purkinje cell axonal degeneration has been identified in
      horses with shivering but its relationship with abnormal hindlimb movement has
      not been elucidated. OBJECTIVES: To characterise surface electromyographic (sEMG)
      hindlimb muscle activity in horses with shivering, correlate with clinical scores
      and examine horses for Purkinje axonal degeneration. STUDY DESIGN: Descriptive
      controlled clinical study. METHODS: The hindlimb of seven shivering and six
      control draught horses were clinically scored. Biceps femoris (BF), vastus
      lateralis (VL), tensor fasciae latae and extensor digitorum longus were recorded
      via sEMG during forward/backward walking and trotting. Integrated (iEMG) and peak
      EMG activity were compared between groups and correlated with clinical locomotor
      exam scores. Sections of the deep cerebellar nuclei (DCN) of six of the seven
      shivering horses were examined with calbindin immunohistochemistry. RESULTS: In
      control horses, backward walking resembled forward walking (right hindlimb peak
      EMG: backward: 47.5 +/- 21.9%, forward: 36.9 +/- 15.7%) but displayed
      significantly higher amplitudes during trotting (76.1 +/- 3.4%). However, in
      shivering horses, backward walking was significantly different from forward
      (backward: 88.5 +/- 21.5%, forward: 49.2 +/- 8.9%), and resembled activity during
      trotting (81.4 +/- 4.8%). Specific to backward walking, mean sEMG amplitude fell
      outside two standard deviations of mean control sEMG for >=25% of the stride in
      the BF for all seven and the VL for six of the seven shivering horses. Locomotor
      exam scores were correlated with peak EMG (r = 0.87) and iEMG (r = 0.87).
      Calbindin-positive spheroids were present in Purkinje axons in DCN of all
      shivering horses examined. MAIN LIMITATIONS: The neuropathological examination
      focused specifically on the DCN and, therefore, we cannot fully exclude
      additional lesions that may have influenced abnormal sEMG findings in shivering
      horses. CONCLUSION: Shivering is characterised by abnormally elevated muscle
      recruitment particularly in BF and VL muscles during backward walking and
      associated with selective Purkinje cell distal axonal degeneration.

PMID- 29356056
TI  - Hypopigmented patches on the buttocks of a 7-year-old boy.

PMID- 29356058
TI  - Cyclophilin D deficiency attenuates mitochondrial perturbation and ameliorates
      hepatic steatosis.
AB  - : Physiological opening of the mitochondrial permeability transition pore (mPTP)
      is indispensable for maintaining mitochondrial function and cell homeostasis, but
      the role of the mPTP and its initial factor, cyclophilin D (CypD), in hepatic
      steatosis is unclear. Here, we demonstrate that excess mPTP opening is mediated
      by an increase of CypD expression induced hepatic mitochondrial dysfunction.
      Notably, such mitochondrial perturbation occurred before detectable triglyceride
      accumulation in the liver of high-fat diet-fed mice. Moreover, either genetic
      knockout or pharmacological inhibition of CypD could ameliorate mitochondrial
      dysfunction, including excess mPTP opening and stress, and down-regulate the
      transcription of sterol regulatory element-binding protein-1c, a key factor of
      lipogenesis. In contrast, the hepatic steatosis in adenoviral overexpression of
      CypD-infected mice was aggravated relative to the control group. Blocking p38
      mitogen-activated protein kinase or liver-specific Ire1alpha knockout could
      resist CypD-induced sterol regulatory element-binding protein-1c expression and
      steatosis. Importantly, CypD inhibitor applied prior to or after the onset of
      triglyceride deposition substantially prevented or ameliorated fatty liver.
      CONCLUSION: CypD stimulates mPTP excessive opening, subsequently causing
      endoplasmic reticulum stress through p38 mitogen-activated protein kinase
      activation, and results in enhanced sterol regulatory element-binding protein-1c
      transcription and hepatic steatosis. (Hepatology 2018;68:62-77).

PMID- 29356057
TI  - Genetic risk of prostate cancer in Ugandan men.
AB  - BACKGROUND: Men of African-ancestry have elevated prostate cancer (PCa) incidence
      and mortality compared to men of other racial groups. There is support for a
      genetic contribution to this disparity, with evidence of genetic heterogeneity in
      the underlying risk alleles between populations. Studies of PCa among African men
      may inform the contribution of genetic risk factors to the elevated disease
      burden in this population. METHODS: We conducted an association study of >100
      previously reported PCa risk alleles among 571 incidence cases and 485 controls
      among Uganda men. Unconditional logistic regression was used to test genetic
      associations and a polygenic risk score (PRS) was derived to assess the
      cumulative effect of the known risk alleles in association with PCa risk. In an
      exploratory analysis, we also tested associations of 17 125 421 genotyped and
      imputed markers genome-wide in association with PCa risk. RESULTS: Of the 111
      known risk loci with a frequency >1%, 75 (68%) had effects that were
      directionally consistent with the initial discovery population,14 (13%) of which
      were nominally significantly associated with PCa risk at P < 0.05. Compared to
      men with average risk (25th -75th percentile in PRS distribution), Ugandan men in
      the top 10% of the PRS, constructed of alleles outside of 8q24, had a 2.9-fold
      (95%CI: 1.75, 4.97) risk of developing PCa; risk for the top 10% increased to
      4.86 (95%CI: 2.70, 8.76) with the inclusion of risk alleles at 8q24. In genome
      wide association testing, the strongest associations were noted with known risk
      alleles located in the 8q24 region, including rs72725854 (OR = 3.37, P = 2.14 *
      10-11 ) that is limited to populations of African ancestry (6% frequency).
      CONCLUSIONS: The ~100 known PCa risk variants were shown to effectively stratify
      PCa risk in Ugandan men, with 10% of men having a >4-fold increase in risk. The
      8q24 risk region was also found to be a major contributor to PCa risk in Ugandan
      men, with the African ancestry-specific risk variant rs72725854 estimated to
      account for 12% of PCa in this population.

PMID- 29356059
TI  - Signs and symptoms that distinguish detrusor underactivity from mixed detrusor
      underactivity and bladder outlet obstruction in male patients.
AB  - AIMS: This study aimed to identify signs and symptoms which show differences
      between men with detrusor underactivity (DU) compared to those with both DU and
      bladder outlet obstruction (BOO). METHODS: One thousand six hundred and twelve
      urodynamic tests on male patients were analyzed retrospectively. Signs and
      symptoms which showed a statistically significant difference between patients
      with DU alone and patients with both DU+BOO were identified. RESULTS: In the DU
      only group, considering only patients without a history of bladder outlet
      surgery, the number of daytime micturitions was lower, maximum voided volume on
      the bladder diary was higher, and slow stream was reported less often, whereas
      urinary tract infections were reported more often than for DU+BOO males. The
      average urine flow rate and abdominal pressure at maximum flow were greater in
      the DU males, compared to the DU+BOO males. CONCLUSIONS: These data suggest that
      by combining symptoms, medical history and signs, that could be measured without
      the need for invasive urodynamics, it may be possible to identify men with DU in
      a non-invasive way. By doing so, men with DU could be separated from men with
      both DU+BOO, with sufficient specificity to allow the use of any new non-surgical
      treatment modalities, such as new and effective medical therapy.

PMID- 29356060
TI  - Utilizing transesophageal echocardiography for placement of pulmonary artery
      catheters.
AB  - OBJECTIVE: Pulmonary artery catheters (PACs) have routinely been positioned by
      wedging into the pulmonary artery before pulling back 1-2 centimeters or
      advancing the PAC several centimeters after achieving a pulmonary artery
      waveform. A rare, major complication is pulmonary artery rupture. This study
      presents transesophageal echocardiography (TEE) for PAC placement by leaving the
      catheter tip at the one o'clock position, upper window short-axis view of the
      ascending aorta at the bifurcation of the pulmonary artery (TEE distance).
      DESIGN: Prospective observational cohort study. SETTING: Large urban academic
      medical center. PARTICIPANTS: 30 males and 30 females undergoing cardiac surgery
      requiring cardiopulmonary bypass. INTERVENTION: TEE was utilized to obtain an
      upper esophageal short-axis view of the aorta with long-axis view of the main and
      right pulmonary arteries. MEASUREMENTS AND RESULTS: The distance between TEE
      position and wedge position was recorded along with patients' gender, height, and
      weight. A correlation was found between TEE and wedge distances (P < .0001).
      There were significant gender differences in TEE distance, with a mean of 43.6 cm
      in females and 46.5 cm in males (P = .0004). The mean wedge distance was 47.5 cm
      in females and 51.9 cm in males (P < .0001). The differences between distances of
      wedge and TEE positions (5.39 cm, males; 3.93 cm, females) were also significant
      (P < .0001). CONCLUSIONS: By securing the PAC at the one o'clock TEE position,
      physicians are assured of a safety margin of several centimeters. This direct
      visualization method for PAC placement may decrease the risk for accidental
      wedging intraoperatively.

PMID- 29356061
TI  - Cohort study from 11 European countries highlighted differences in the use and
      efficacy of hypothermia prevention strategies after very preterm birth.
AB  - AIM: This study investigated the different strategies used in 11 European
      countries to prevent hypothermia, which continues to affect a large proportion of
      preterm births in the region. METHODS: We examined the association between the
      reported use of hypothermia prevention strategies in delivery rooms and body
      temperatures on admission to neonatal intensive care units (NICUs) in 5861
      infants born at 22 + 0 to 31 +6 weeks of gestation. The use of plastic bags,
      wraps, caps, exothermic heat and mattresses was investigated. RESULTS: The
      proportion of infants born in units that systematically used one or more
      hypothermia prevention strategies was 88.2% and 50.9% of those infants were
      hypothermic on admission to NICUs. Of the 9.6% born in units without systematic
      hypothermia prevention, 73.2% were hypothermic. Only 2.2% of infants were born in
      units with no reported prevention strategies. Lower gestational age increased the
      probability of hypothermia. No significant differences were found between the
      various hypothermia prevention strategies. Hyperthermia was seen in 4.8% of all
      admitted infants. CONCLUSION: Very preterm infants had lower risks of hypothermia
      on NICU admission if the unit used systematic prevention strategies. All the
      strategies had similar effects, possibly due to implementation rather than a
      strategy's specific efficacy.

PMID- 29356062
TI  - Mouldable, thermoplastic, glue-on frog-supportive shoes change hoof kinetics in
      normal and obese Shetland ponies.
AB  - BACKGROUND: Obesity and hyperinsulinaemia are frequently encountered in the
      equine population and risk factors for the development of laminitis. There are
      many options for hoof support that claim a beneficial effect, but often the
      scientific evidence is scarce. OBJECTIVES: To quantify the effect of frog
      supportive shoes on hoof kinetics in normal and obese ponies. STUDY DESIGN:
      Controlled in vivo trial. METHODS: Ten Shetland mares (n = 10) with a normal (n =
      5) or obese (n = 5) body condition were led over a dynamically calibrated
      pressure plate before (T0), immediately after (T1) and 72 h (T2) after
      application of the shoes. The following locomotor variables were measured: stance
      duration (StDur), vertical impulse (VI), peak vertical force (PVF), time to PVF
      and time from PVF to lift off. The hoof print was divided into a toe and heel
      region and the StDur toe-heel index was calculated. The toe-heel hoof balance
      curves of the vertical force were plotted throughout the stance phase. RESULTS:
      The VI and PVF increased significantly 72 h after application of the shoes, when
      compared with T0 and T1. The StDur toe-heel index and toe-heel balance curves
      were significantly different between the normal and obese ponies. These variables
      became more comparable between the groups after application of the frog
      supportive shoes. MAIN LIMITATIONS: It would have been interesting to measure the
      effect of the shoe in patients with acute laminitis. However, this would have had
      major welfare implications. CONCLUSIONS: The obese ponies moved more carefully
      than the normal group, demonstrated by a decreased loading of the toe area. The
      data illustrate that the ponies became more comfortable 72 h after application of
      the shoes, with a pronounced effect in the obese group. Thus, these results
      suggest that frog-supportive shoes could be beneficial, especially for obese
      ponies.

PMID- 29356063
TI  - Development and feasibility assessment of a 3 day electronic bladder diary as an
      app for smart-phone.
AB  - AIMS: To develop a 3 day bladder diary (BD) as an easy-to-use application for
      smart-phone (eDM3d). To test its feasibility and acceptance in a reduced number
      of patients. METHODS: An external agency developed the eDM3d following the
      structure of the Spanish validated 3 day BD (DM3d(c)), which includes a frequency
      volume chart, the assessment of the grade of urgency, the incontinence events and
      fluid intake. The eDM3d consisted in a main interface of four buttons ("wake up,"
      "go to bed," "urinate," "drink") which had to be clicked to create an event.
      Results were automatically transferred to an internet server to obtain an
      electronic report. We recruited 25 patients with overactive bladder syndrome or
      nocturia and previous experience on paper BD. They were asked to complete the
      eDM3d. Finally, a direct question about satisfaction was answered: "If you had to
      complete a BD again, would you choose the paper or the app version?" RESULTS:
      Three patients (12%) did not complete the eDM3d, 1 patient (4%) completed 2 days
      of the eDM3d and did not register volumes of micturition nor fluid intake, 1
      patient (4%) completed all 2 days variables and 20 patients (80%) completed all 3
      day variables. Regarding satisfaction, 19 patients (86.4%) would choose the app
      version, 2 patients (9.1%) would choose a paper version and 1 patient (4.5%)
      would choose either indistinctly. CONCLUSIONS: The eDM3d is a useful tool easily
      filled in by patients with a high satisfaction rate. Adequate validation of the
      eDM3d is required.

PMID- 29356065
TI  - Erratum.

PMID- 29356064
TI  - Noonan syndrome with multiple lentigines and associated craniosynostosis.

PMID- 29356066
TI  - The Morality of Disordered Eating and Recovery in Southern Italy.
AB  - Scholars have traced the processes through which moral subjectivities are
      constituted in culturally meaningful ways through eating disorders and recovery
      practices, demonstrating how subjective meanings of eating disorders and recovery
      from them are imbued with moral undertones and become meaningful ways of existing
      within specific historical and cultural contexts. Drawing on ethnographic
      insights and interviews with young women with disordered eating histories in
      southern Italy, we show how suffering from eating disorders and recovery from
      them enables women to retool their identities and craft moral selves. We draw
      attention to the value of medical anthropology in the care and comprehension of
      well-being of girls and women suffering from disordered eating.

PMID- 29356067
TI  - Reply from authors to the Letter to the Editor on RE: Futyma et al. use of
      uroflow parameters in diagnosing an overactive bladder-Back to the drawing board
      and ICS News 613.

PMID- 29356068
TI  - Could echocardiography determine whether spontaneous coronary dissection is
      occasionally associated with Takotsubo syndrome?

PMID- 29356069
TI  - Association of circulating resistin, leptin, adiponectin and visfatin levels with
      Behcet disease: a meta-analysis.
AB  - BACKGROUND: Behcet disease (BD) is a chronic inflammatory disease. Adipokines are
      synthesized in adipose tissue, and have been reported to play important roles in
      the pathogenesis of autoimmune and inflammatory diseases, including BD. AIM: To
      evaluate the relationship between circulating blood adipokine levels and BD.
      METHODS: We conducted a meta-analysis of papers reporting on serum/plasma
      resistin, leptin, adiponectin and visfatin levels in patients with BD and in
      healthy controls (HCs). We identified 82 relevant studies using electronic and
      manual search methods, and selected 16 studies for full-text review based on the
      title and abstract. Two of these were later excluded (one was a review, one had
      no data), leaving 14 articles that met the inclusion criteria for this meta
      analysis. RESULTS: The 14 included studies assessed 637 patients with BD and 520
      HCs. Compared with the HCs, the BD group had significantly higher levels of
      leptin [standardized mean difference (SMD) = 0.68, 95% CI 0.15-1.21, P = 0.01].
      Levels of resistin (SMD = 0.51, 95% CI 0.92-0.918, P = 0.02) and adiponectin (SMD
      = 0.31, 95% CI 0.06-0.56, P = 0.02) were significantly higher in the BD group
      after adjustment for age, sex and body mass index (BMI), but not without such
      adjustment (resistin: (SMD = 0.38, 95% CI -0.18 to 0.93, P = 0.19; adiponectin:
      SMD = -0.59, 95% CI -2.23 to 1.06, P = 0.48). A significantly lower visfatin
      level was found in the BD group with adjustment (SMD = -1.70, 95% CI -2.14 to 
      1.25, P < 0.001) but not without adjustment (SMD = 0.31, 95% CI -0.21 to 0.82, P
      = 0.24). CONCLUSIONS: Our meta-analysis revealed significantly higher circulating
      resistin, leptin and adiponectin levels and lower visfatin levels in patients
      with BD than in HCs, indicating that adipokines probably play an important role
      in BD pathogenesis.

PMID- 29356070
TI  - Mitral leaflet separation to evaluate the severity of mitral stenosis: Validation
      of the index by transesophageal three-dimensional echocardiography.
AB  - BACKGROUND: Determining severity of mitral stenosis (MS) by planimetry of mitral
      valve orifice area (MVA) has been a challenging issue in clinical practice,
      especially for less experienced cardiologists. Mitral leaflet separation (MLS)
      has shown a good correlation with MVA measurements. However, it has never been
      validated against multiplane 3DTEE planimetry (MVA3D ). We aimed to evaluate the
      accuracy of MLS index (MLSI2D ) in predicting MS severity. METHODS: We
      prospectively enrolled 144 patients with MS who underwent clinically indicated
      2DTTE and 3DTEE. MLSI2D was yield by averaging the maximal leaflet tip distance
      in diastole, in parasternal long-axis and apical four-chamber views. MVA3D was
      used as the reference method. RESULTS: MLSI2D showed an excellent discriminatory
      ability between different grades of MS (P < .001). There was a significant
      positive correlation between MLSI2D and MVA3D (r = .93, P < .001) irrespective of
      concurrent mitral regurgitation (r = .94, P < .001) and/or atrial fibrillation (r
      = .92, P < .001). By receiver operating characteristic (ROC) curves, MLSI2D  <=
      8.6 mm showed 100% sensitivity and 76% specificity for very severe MS. MLSI2D  >=
      11.2 mm determined progressive MS with 100% sensitivity and 82% specificity. The
      study population was then divided into a derivation group and a validation group.
      A regression equation for MVA by MLSI2D was derived in first group. Then, the MVA
      was calculated by this equation in validation group and was not significantly
      different from MVA3D . CONCLUSION: MLSI2D showed an excellent ability to assess
      MS severity and correlates well with planimetered MVA measured by 3DTEE.

PMID- 29356071
TI  - The anti-inflammatory IFITM genes ameliorate colitis and partially protect from
      tumorigenesis by changing immunity and microbiota.
AB  - Inflammation plays pivotal roles in different stages of tumor development.
      Screening for predisposing genetic abnormalities and understanding the roles
      these genes play in the crosstalk between immune and cancer cells will provide
      new targets for cancer therapy and prevention. The interferon inducible
      transmembrane (IFITM) genes are involved in pathogenesis of the gastro-intestinal
      tract. We aimed at delineating the role of IFITM3 in colonic epithelial
      homeostasis, inflammation and colitis-associated tumorigenesis using IFITM3
      deficient mice. Chemical induction of colitis in IFITM3-deficient mice results in
      significantly increased clinical signs of inflammation and induction of invasive
      tumorigenesis. Bone marrow transplantation showed that cells of the hematopoietic
      system are responsible for colitis deterioration. In these mice, impaired
      cytokine expression skewed inflammatory response toward pathogenic Th17 with
      reduced expression of the anti-inflammatory cytokine IL10 during the recovery
      phase. Intriguingly, mice lacking the entire IFITM locus developed spontaneous
      chronic colitis from the age of 14 weeks. Sequencing the 16S rRNA of naive mice
      lacking IFITM3 gene, or the entire locus containing five IFITM genes, revealed
      these mice had significant bacterial differences from their wild-type
      littermates. Our novel results provide strong evidence for the essential role of
      IFITM genes in ameliorating colitis and colitis-associated tumorigenesis.

PMID- 29356072
TI  - Flash forward: a review of flash glucose monitoring.
AB  - The FreeStyle Libre flash glucose monitor became available on prescription
      (subject to local health authority approval) in all four nations of the UK from
      November 2017, a watershed moment in the history of diabetes care. Calibration
      free, the FreeStyle Libre is a disc worn on the arm for 14 days which is designed
      largely to replace the recommended 4-10 painful finger-stick blood glucose tests
      required each day for the self-management of diabetes. This review discusses
      clinical data from randomized and observational studies, considers device
      accuracy metrics and deliberates its popularity and the potential challenges that
      this new device brings to diabetes care in the UK. In randomized trials,
      FreeStyle Libre use is associated with a reduction in hypoglycaemia and, in
      observational studies, improvements in HbA1c levels. User satisfaction is high
      and adverse events are low. Accuracy of the FreeStyle Libre is comparable to
      currently available real-time continuous glucose monitors in adults, children and
      during pregnancy; the cost of the FreeStyle Libre is lower. Glucose data can be
      visualized in multiple devices and platforms, and summarized in an ambulatory
      glucose profile to aid pattern recognition and insulin dose adjustment. There is
      a need for appropriate education, of both users and healthcare professionals, to
      harness the full benefits. Further randomized studies to assess the long-term
      impact on HbA1c , particularly in those with high baseline HbA1c and in specific
      age groups, such as adolescents and young adults, are warranted. The potential
      impact on complications, is yet to be realized.

PMID- 29356073
TI  - National population-based cohort study found that visual-motor integration was
      commonly affected in extremely preterm born children at six-and-a-half years.
AB  - AIM: This study aimed to explain the relationship between visual-motor
      integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the
      influence of perinatal variables, cognition, manual dexterity and
      ophthalmological outcomes. METHODS: This was part of the population-based
      national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355
      children, born at a gestational age of <27 weeks from April 2004 to March 2007,
      and 364 term-born controls. At six-and-a-half years of age, we assessed VMI,
      cognitive function, motor skills and vision. VMI impairment was classified as <-1
      standard deviation (SD). RESULTS: The mean (SD) VMI score was 87 (+/-12) in
      preterm children compared to 98 (+/-11) in controls (p < 0.001). VMI impairment
      was present in 55% of preterm infants and in 78% of children born at 22-23 weeks.
      Male sex and postnatal steroids showed a weak association with poorer visual
      motor performance, whereas low manual dexterity and cognitive function showed a
      stronger association. CONCLUSION: Poor VMI performance was common in this EXPRESS
      cohort of children born EPT. Its strong association to cognition and manual
      dexterity confirms that all of these factors need to be taken into account when
      evaluating risks in preterm born children.

PMID- 29356074
TI  - Diabetes technology: improving care, improving patient-reported outcomes and
      preventing complications in young people with Type 1 diabetes.
AB  - With the evolution of diabetes technology, those living with Type 1 diabetes are
      given a wider arsenal of tools with which to achieve glycaemic control and
      improve patient-reported outcomes. Furthermore, the use of these technologies may
      help reduce the risk of acute complications, such as severe hypoglycaemia and
      diabetic ketoacidosis, as well as long-term macro- and microvascular
      complications. In addition, diabetes technology can have a beneficial impact on
      psychosocial health by reducing the burden of diabetes. Unfortunately, diabetes
      goals are often unmet and people with Type 1 diabetes too frequently experience
      acute and long-term complications of this condition, in addition to often having
      less than ideal psychosocial outcomes. Increasing realization of the importance
      of patient-reported outcomes is leading to diabetes care delivery becoming more
      patient-centred. Diabetes technology in the form of medical devices, digital
      health and big data analytics have the potential to improve clinical care and
      psychosocial support, resulting in lower rates of acute and chronic
      complications, decreased burden of diabetes care, and improved quality of life.

PMID- 29356075
TI  - Assessment of medication adherence and treatment satisfaction in Japanese
      patients with psoriasis of various severities.
AB  - Psoriasis is a chronic, relapsing, inflammatory keratotic skin disease. To
      elucidate the medication adherence and treatment satisfaction, we performed a
      questionnaire survey using the eight-item Morisky Medication Adherence Scale
      (MMAS-8) and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM
      9) of 163 psoriatic patients who regularly visited hospitals or clinics. To
      assess the relationship between the MMAS-8/TSQM-9 outcomes and severity of
      psoriasis, two different clinical severity indices were used: the Psoriasis Area
      and the Severity Index (PASI) for disease severity and the Psoriasis Disability
      Index (PDI) for quality of life (QOL) impairment. The MMAS-8 score for oral
      medication was significantly higher than that for topical medication. The oral
      and topical MMAS-8 scores were significantly correlated with the PDI score, but
      not with the PASI score, indicating that QOL impairment lowered treatment
      motivation. All of the TSQM-9 domain scores (effectiveness, convenience and
      global satisfaction) were significantly correlated with both the PASI and PDI
      scores, suggesting that patients whose skin and QOL conditions were under good
      control had high satisfaction with treatment. Patients treated with biologics had
      higher satisfaction than those treated with non-biologics.

PMID- 29356077
TI  - Static and dynamic pupillometry data of healthy individuals.
AB  - BACKGROUND: This study sought to determine normative static and dynamic
      pupillometry data in different age groups in a healthy population, and to
      investigate the effects of age on pupillometric characteristics. METHODS:
      Pupillometry measurements were undertaken on 155 healthy participants using an
      automatic quantitative pupillometry system. Static pupillometry measurements were
      undertaken; these included scotopic pupil diameter (PD), mesopic PD, low photopic
      PD and high photopic PD values. Dynamic pupillometry measurements were
      undertaken, including resting diameter, amplitude of pupil contraction, latency
      of pupil contraction, duration of pupil contraction, velocity of pupil
      contraction, latency of pupil dilation, duration of pupil dilation and velocity
      of pupil dilation. RESULTS: Overall, 69 (44.5 per cent) participants were male
      and 86 (55.5 per cent) were female, with a mean age of 29.7 +/- 17.8 years.
      Neither static nor dynamic pupillometry measurements varied significantly between
      males and females. Age was inversely and moderately correlated with each of the
      static pupillometric characteristics (p < 0.05). Resting diameter, velocity of
      pupil contraction, and velocity of pupil dilation values were inversely and
      moderately correlated with age (p < 0.001, r = -0.63; p < 0.001, r = -0.47; and p
      < 0.001, r = -0.34, respectively). Latency of pupil contraction was positively
      and moderately correlated with age (p = 0.002, r = 0.29). CONCLUSIONS: The
      current study presents population-specific normative data on static and dynamic
      pupillometry values in different age groups and the effect of age on pupillary
      characteristics.

PMID- 29356076
TI  - Successful management of steroid-resistant vascular tumors associated with the
      Kasabach-Merritt phenomenon using sirolimus.
AB  - Vascular tumors associated with Kasabach-Merritt phenomenon (KMP) are life
      threatening and the mortality is as high as 10-30%. Steroids are considered the
      primary choice for drug therapy. However, there are many steroid-resistant cases.
      In the present study, analyzed data are presented to support the use of sirolimus
      in clinical practise for the treatment of corticosteroid-resistant vascular
      tumors with KMP in eight infants between June 2015 and April 2017 in a single
      hospital. The time to initial response was 6.8 +/- 2.7 days. The average
      stabilization time for the platelet count was 19.1 +/- 8.5 days. At the time of
      publication, the average duration of sirolimus treatment was 14.1 +/- 4.0 months,
      and the average time for sirolimus treatment as a single agent was 12.6 +/- 4.2
      months. The side-effects were tolerable and included oral ulcer, fever, pain,
      skin rash and transient ascension of serum transaminase and cholesterol. Our
      study indicated that sirolimus therapy is an effective and safe method for the
      treatment of corticosteroid resistant vascular tumors associated with KMP in
      infants.

PMID- 29356078
TI  - Diabetes and technology in 2030: a utopian or dystopian future?
AB  - The ability of an individual living with diabetes to have human-to-human contact
      with their healthcare provider is not keeping pace with the number of people
      developing diabetes. From a futurist perspective, however, this dichotomy of
      diabetes care represents an opportunity for digital healthcare. The focus of
      technological innovation is unlikely to be the replacement of the
      multidisciplinary diabetes team but rather the provision of meaningful individual
      and family support between clinic visits and, on a larger scale, the facilitation
      of population health management for diabetes. We can also expect to see new
      therapies, including implantable drug delivery systems, automated closed-loop
      systems and miniaturized non-invasive glucose monitoring systems. New digital
      health technologies will create a 'digital diabetes ecosystem' to enhance rather
      than devolve care from humans. Concerns related to data privacy and ownership
      will inevitably rise, thus a future for diabetes care relying heavily on
      technology is not inevitably utopian. Nevertheless, revolutions in the
      development of novel sensors, accumulation of 'big data', and use of artificial
      intelligence will provide exciting opportunities for preventing, monitoring and
      treating diabetes in the near future.

PMID- 29356079
TI  - Molecular characterization of diarrheagenic Escherichia coli pathotypes:
      Association of virulent genes, serogroups, and antibiotic resistance among
      moderate-to-severe diarrhea patients.
AB  - BACKGROUND: Diarrheagenic Escherichia coli (DEC) signifies as an important
      etiological agent of moderate-to-severe diarrhea. This study was primarily
      focused on molecular identification of DEC pathotypes; their association with
      serogroups and estimates of resistance profiles against different antibiotics
      regime. METHODS: Five hundred seventy-two stool specimens from diarrhea patients
      were investigated for DEC pathotypes. Molecular pathotypes were identified by
      amplification of virulence genes associated with distinct pathotypes followed by
      sequencing. Diarrhea is a self-limiting disease, however, severity and
      persistence of infection suggest antibiotic use. Therefore, AST and MIC were
      determined against common antibiotic regimen. Correlations between molecular
      pathotypes and serogroups were analyzed by somatic "O" antigen serotyping.
      RESULTS: The present findings reveal incidence of DEC as an etiological agent up
      to a level of 21% among all diarrheal age groups. DEC infection rate was higher
      in children. Enteropathogenic E. coliEPEC, a molecular pathotype of DEC, was
      found as a predominant pathotype with highest frequency of 13.7%. Two other
      molecular pathotypes enterotoxigenic E. coli (ETEC) and enteroaggregative E. coli
      (EAEC) accounted for 5.7% and 1.3%, respectively for all diarrhea incidences.
      Serological analysis deciphered somatic antigens O26, O2, and O3 as major
      serogroups identified among EPEC, ETEC, and EAEC pathotypes, respectively. All
      DEC pathotypes exhibited high levels of antibiotic resistance except for
      cotrimoxazole and norfloxacin. CONCLUSION: Comprehensive molecular
      characterization of DEC pathotypes, their incidence estimates, and antibiogram
      patterns will help in ascertaining better diagnostic and therapeutic measures in
      management of diarrheal diseases.

PMID- 29356080
TI  - Striving to meet targets for ideal treatment of acute myocardial infarction in
      Brazil: Data from the Midwest region.
AB  - OBJECTIVES: To evaluate the systematic chain of care for patients with acute ST
      elevation myocardial infarction (STEMI) referred for primary angioplasty in a
      capital city in Midwestern Brazil. BACKGROUND: Acute myocardial infarction is
      recognized as an important cause of morbidity and mortality and as a public
      health problem worldwide. Early specialized care is crucial for a good prognosis.
      METHODS: All STEMI patients receiving care through the public health system at
      two tertiary care centers from March 2012 to June 2014 were retrospectively
      analyzed. Symptom onset-to-balloon time and door-to-balloon time were analyzed
      and compared with current guideline recommendations. RESULTS: A total of 835
      patients were included. Median symptom onset-to-balloon time was 32 h. A total of
      783 (94%) patients had had symptoms for more than 12 h and 507 (61%) for more
      than 24 h. Only 51 (6%) patients arrived within 12 h of symptom onset and were
      treated with primary angioplasty. Among these patients, median door-to-balloon
      time was 37 min, in accordance with guideline recommendations. CONCLUSION:
      Treatment of STEMI through the public health system in a capital city in
      Midwestern Brazil falls short of the recommended guidelines due to failure in the
      initial links of the chain of care. This potentially reversible failure has an
      important impact on patient outcomes and on health care burden.

PMID- 29356081
TI  - When are two interventions the same? Implications for reporting guidelines in
      education.

PMID- 29356082
TI  - Don't miss the boat: maximise ad hoc teaching with general practice trainees.

PMID- 29356084
TI  - You can't put a value on that... Or can you? Economic evaluation in simulation
      based medical education.

PMID- 29356085
TI  - The struggle to support the transition to medical educator.

PMID- 29356086
TI  - Widening access: plant the seeds earlier.

PMID- 29356087
TI  - Point-of-care ultrasound and undergraduate medical education: the perils of
      learning a new way to see.

PMID- 29356088
TI  - Exposure of the developing heart to diabetic environment and early cardiac
      assessment: A review.
AB  - Hyperglycemia during organogenesis is associated with an increased risk of
      congenital cardiac defects (CHDs). The pathophysiology leading to CHDs is not
      completely uncovered. However, elevated oxidative stress is considered to be the
      primary trigger that causes CHDs in fetuses of diabetic mothers. Maternal
      diabetes has been found to increase the risk for all types of CHDs. Diabetes may
      also impact the fetal cardiac performance at all gestational ages. Early
      detection of CHDs has certain advantages, such as making early decision about
      termination of pregnancy, enabling early genetic testing, and early reassurance
      if scan is normal. Combined transabdominal and transvaginal approach at 13-14
      weeks of gestation is a reasonable strategy to assess fetal heart in diabetic
      women. Diagnostic accuracy of early fetal echocardiography has reached to above a
      reasonable cutoff when it is done in the late first trimester or early second
      trimester in the hands of expert sonographers. However, the literature is less
      certain to provide a firm conclusion about functional heart assessment in fetuses
      of diabetic mothers.

PMID- 29356089
TI  - Adult presentation of ALCAPA: Echo and CT diagnosis.
AB  - A healthy 20-year-old male presented with aborted sudden death. Both thoracic
      echocardiography and cardiac computed tomographic angiography demonstrated the
      characteristic findings of ALCAPA noting a dilated and tortuous right coronary
      artery, dilated coronary collateral arteries within the interventricular septum
      or along the surface of the heart, and visualization of the left coronary artery
      origin from the posterior aspect of the main pulmonary artery. Both imaging
      modalities demonstrated all three characteristic findings of this rare coronary
      anomaly and served as complementary imaging studies for surgical correction.

PMID- 29356090
TI  - Useful information provided by graphic displays of automated cell counter in
      hematological malignancies.
AB  - BACKGROUND: Automated cell counters have become more and more sophisticated with
      passing years. The numerical and graphic data both provide useful clues for
      suspecting a diagnosis especially when the workload is very high. AIM: We present
      our experience of useful information provided by graphic displays of an automated
      cell counter in hematological malignancies in a cancer hospital where a large
      number of complete blood count (CBC) requests are received either before or
      during chemotherapy. This study was conducted to assess the usefulness of
      hematology cell counter, viz. WBC-Diff (WBC differential), WBC/BASO (WBC
      basophil) and IMI (immature myeloid information) channel scatter plots, and the
      flaggings generated in various hematological malignancies. MATERIAL & METHODS:
      The graphic displays have been compiled over a period of 1 year (October 2015
      September 2016) from blood samples of various solid and hematological
      malignancies (approximately 400 per day) received for routine CBC in the
      laboratory. Approximately 50 000 scattergrams have been analyzed during the study
      period. The findings were confirmed by peripheral blood smear examination.
      RESULTS: The scattergram analysis on XE-2100 is very sensitive as well as
      specific for diagnosing acute leukemia, viz. acute myeloid leukemia, acute
      lymphoblastic leukemia; chronic myeloproliferative disorders, viz. chronic
      myeloid leukemia; and chronic lymphoproliferative disorder especially chronic
      lymphocytic leukemia. CONCLUSION: It is suggested that the laboratories using the
      hematology analyzers be aware of graphic display patterns in addition to
      flaggings generated which provide additional information and give clue toward the
      diagnosis even before peripheral smear examination.

PMID- 29356091
TI  - Alternatives to animal testing in basic and preclinical research of atopic
      dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing
      prevalence, especially in industrialized countries. Roughly 25% of the children
      and 1%-3% of adults are affected. Although significant progress has been made in
      the understanding of the pathogenesis of AD, many aspects remain poorly
      understood. Moreover, there is a pressing need for improved therapeutic options.
      Studies to elucidate the pathophysiological pathways of AD and to identify novel
      therapeutic targets over the last few decades have been conducted almost
      exclusively in animal models. However, in vitro approaches such as 3D skin
      disease models have recently emerged due to an increasing awareness of distinct
      interspecies-related differences that hamper the effective translation of results
      from animal models to humans. In addition, there is growing political and social
      pressure to develop alternatives to animal models according to the 3Rs principle
      (reduction, refinement and replacement of animal models).

PMID- 29356092
TI  - Reliability of a two-colour chewing gum test to assess masticatory performance in
      complete denture wearers.
AB  - The aim of this study was to test the reliability of a method to measure the
      masticatory performance of complete denture wearers employing a colour-mixing
      ability test and assessment by visual and electronic colourimetric analysis. A
      sample of 75 subjects was selected from patients who received new conventional
      complete dentures. Masticatory tests were performed using a two-colour chewing
      gum that was masticated for 5, 10, 20, 30 and 50 chewing cycles, performed in a
      random order. The mixing level of the two colours of the chewed gum was assessed
      visually by two independent raters based on a 5-point ordinal scale. The
      specimens were flattened into a 1-mm-width wafer, scanned and saved as a two
      sided digital image. Each pair of images was submitted to an electronic
      colourimetric analysis to assess the level of colour mixture, measured by the
      circular variance of hue (VOH). Overall inter- and intra-rater agreements in
      visual analysis were 64% and 68%, respectively (almost 99% of scores ranged
      within +/-1 point), whilst overall weighted kappa was >0.80. A proportional
      increase in the level of mixture occurred with increased number of chewing cycles
      (P < .001). Similarly, VOH and the visual analysis were highly correlated (r = 
      .89; P < .001). Bland-Altman plots revealed excellent agreement and extremely low
      systematic error between duplicated VOH measures. It was concluded that the two
      colour chewing gum test is a reliable method to assess the masticatory
      performance in complete denture wearers using both visual and electronic
      colourimetric analyses.

PMID- 29356093
TI  - A new checkpoint for Natural Killer cell activation.

PMID- 29356094
TI  - Beta-catenin promotes macrophage-mediated acute inflammatory response after
      myocardial infarction.
AB  - Regulatory mechanisms for acute inflammatory responses post myocardial infarction
      (MI) have yet to be fully understood. In particular, the mechanisms by which
      cardiac macrophages modulate MI-induced myocardial inflammation remains unclear.
      In this study, using a mouse MI model, we showed that beta-catenin-mediated
      signaling was activated in cardiac macrophages post-MI, especially in Ly-6C
      positive proinflammatory macrophages. Using a RAW264.7-based beta-catenin
      reporter cell line, we confirmed the presence of active beta-catenin and its
      downstream signaling in cardiac macrophages after MI. Moreover, lentivirus
      mediated inducible expression of constitutively active beta-catenin revealed that
      beta-catenin plays a role in promoting the inflammatory response by RAW264.7
      cells. Depletion of endogenous macrophages and adoptive transfer of active beta
      catenin-expressing RAW264.7 cells resulted in enhancement of acute myocardial
      inflammation in recipient mice after MI, as demonstrated by elevated levels of
      lymphocyte infiltrates and increased expression of proinflammatory cytokines.
      However, infarct volume, myocardial tissue repair, and left ventricle function
      were not influenced by the expression of active beta-catenin in the adoptive
      transfer assay. Our research has demonstrated that beta-catenin-mediated
      signaling is important for cardiac macrophages to modulate post-MI inflammatory
      responses. These findings may be valuable for developing novel therapeutic
      strategies for MI.

PMID- 29356095
TI  - Familial Congenital Methemoglobinemia in Pomeranian Dogs Caused by a Missense
      Variant in the NADH-Cytochrome B5 Reductase Gene.
AB  - BACKGROUND: In veterinary medicine, congenital methemoglobinemia associated with
      nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency
      is rare. It has been reported in several breeds of dogs, but little information
      is available about its etiology. OBJECTIVES: To analyze the NADH-cytochrome b5
      reductase gene, CYB5R3, in a Pomeranian dog family with methemoglobinemia
      suspected to be caused by congenital b5R deficiency. ANIMALS: Three Pomeranian
      dogs from a family with methemoglobinemia were analyzed. Five healthy beagles and
      5 nonrelated Pomeranian dogs without methemoglobinemia were used as controls.
      METHODS: Methemoglobin concentration, b5R activity, and reduced glutathione (GSH)
      concentration were measured, and a turbidity index was used to evaluate Heinz
      body formation. The CYB5R3 genes of the affected dog and healthy dogs were
      analyzed by direct sequencing. RESULTS: Methemoglobin concentrations in
      erythrocytes of the affected dogs were remarkably higher than those of the
      control dogs. The b5R activity of the affected dogs was notably lower than that
      of the control dogs. DNA sequencing indicated that this Pomeranian family carried
      a CYB5R3 gene missense variant (ATC->CTC at codon 194) that resulted in the
      replacement of isoleucine (Ile) by leucine (Leu). CONCLUSIONS AND CLINICAL
      IMPORTANCE: This dog family had familial congenital methemoglobinemia caused by
      b5R deficiency, which resulted from a nonsynonymous variant in the CYB5R3 gene.
      This variation (c.580A>C) led to an amino acid substitution (p.Ile194Leu), and
      Ile194 was located in the proximal region of the NADH-binding motif. Our data
      suggested that this variant in the canine CYB5R3 gene would affect function of
      the b5R in erythrocytes.

PMID- 29356096
TI  - Investigation of the Role of Campylobacter Infection in Suspected Acute
      Polyradiculoneuritis in Dogs.
AB  - BACKGROUND: Acute polyradiculoneuritis (APN) is an immune-mediated peripheral
      nerve disorder in dogs that shares many similarities with Guillain-Barre syndrome
      (GBS) in humans, in which the bacterial pathogen Campylobacter spp. now is
      considered to be a major triggering agent. Little information is available
      concerning the relationship between APN and Campylobacter spp. in dogs.
      HYPOTHESIS/OBJECTIVES: To estimate the association between Campylobacter spp.
      infection and APN. Associations with additional potential risk factors also were
      investigated, particularly consumption of raw chicken. ANIMALS: Twenty-seven
      client-owned dogs suffering from suspected APN and 47 healthy dogs, client-owned
      or owned by staff members. METHODS: Case-control study with incidence density
      based sampling. Fecal samples were collected from each enrolled animal to perform
      direct culture, DNA extraction, and polymerase chain reaction (PCR) for detection
      of Campylobacter spp. In some cases, species identification was performed by
      sequence analysis of the amplicon. Data were obtained from the medical records
      and owner questionnaires in both groups. RESULTS: In cases in which the fecal
      sample was collected within 7 days from onset of clinical signs, APN cases were
      9.4 times more likely to be positive for Campylobacter spp compared to control
      dogs (P < 0.001). In addition, a significant association was detected between
      dogs affected by APN and the consumption of raw chicken (96% of APN cases; 26% of
      control dogs). The most common Campylobacter spp. identified was Campylobacter
      upsaliensis. CONCLUSIONS AND CLINICAL IMPORTANCE: Raw chicken consumption is a
      risk factor in dogs for the development of APN, which potentially is mediated by
      infection with Campylobacter spp.

PMID- 29356097
TI  - Association of single nucleotide polymorphisms in WNT genes with the risk of
      nonsyndromic cleft lip with or without cleft palate.
AB  - Nonsyndromic cleft lip with or without cleft palate is a common congenital
      deformity worldwide with multifaceted etiology. Interaction of genes and
      environmental factors has been indicated to be related with susceptibility to
      nonsyndromic cleft lip with or without cleft palate. Some WNT genes which are
      involved in craniofacial embryogenesis may play a key role in the pathogenesis of
      nonsyndromic cleft lip with or without cleft palate. In the present study, we
      aimed to inspect the relationship between WNT3 (rs3809857 and rs9890413), WNT3A
      (rs752107 and rs3121310), and WNT10a rs201002930 (c.392 C>T) polymorphisms and
      nonsyndromic cleft lip with or without cleft palate in an Iranian population. The
      present case-control study was carried out on 120 unrelated nonsyndromic cleft
      lip with or without cleft palate patients and 112 healthy subjects. The variants
      were genotyped by polymerase chain reaction-restriction fragment length
      polymorphism method. The findings suggest that the rs3809857 polymorphism
      significantly decreased the risk of nonsyndromic cleft lip with or without cleft
      palate in codominant (odds ratio = 0.16, 95% confidence interval = 0.03-0.75, P =
      0.020, TT vs GG), recessive (odds ratio = 0.16, 95% confidence interval = 0.03
      0.72, P = 0.009, TT vs GG + GT) inheritance models. The rs9890413 variant
      marginally decreased the risk of nonsyndromic cleft lip with or without cleft
      palate in codominant (odds ratio = 0.41, 95% confidence interval = 0.17-0.99, P =
      0.047, AG vs AA) model. Regarding C392T variant, the findings revealed that this
      variant significantly decreased the risk of nonsyndromic cleft lip with or
      without cleft palate in codominant (odds ratio = 0.24, 95% confidence interval =
      0.10-0.58, P = 0.002, CT vs CC) and allele (odds ratio = 0.26, 95% confidence
      interval = 0.11-0.62, P = 0.002, T vs C) models. No significant association was
      observed between the rs752107 and rs3121310 variants and risk/protection of
      nonsyndromic cleft lip with or without cleft palate. Stratified analysis showed
      that WNT10a rs201002930 (c.392 C>T) significantly decreased the risk of cleft lip
      with cleft palate and cleft palate only. In summary, the results suggest an
      association between WNT genes polymorphisms and the risk nonsyndromic cleft lip
      with or without cleft palate in a sample of the southeast Iranian population.

PMID- 29356099
TI  - Erratum.

PMID- 29356098
TI  - A systematic review of the diagnostic accuracy of automated tests for cognitive
      impairment.
AB  - OBJECTIVE: The aim of this review is to determine whether automated computerised
      tests accurately identify patients with progressive cognitive impairment and, if
      so, to investigate their role in monitoring disease progression and/or response
      to treatment. METHODS: Six electronic databases (Medline, Embase, Cochrane,
      Institute for Scientific Information, PsycINFO, and ProQuest) were searched from
      January 2005 to August 2015 to identify papers for inclusion. Studies assessing
      the diagnostic accuracy of automated computerised tests for mild cognitive
      impairment (MCI) and early dementia against a reference standard were included.
      Where possible, sensitivity, specificity, positive predictive value, negative
      predictive value, and likelihood ratios were calculated. The Quality Assessment
      of Diagnostic Accuracy Studies tool was used to assess risk of bias. RESULTS:
      Sixteen studies assessing 11 diagnostic tools for MCI and early dementia were
      included. No studies were eligible for inclusion in the review of tools for
      monitoring progressive disease and response to treatment. The overall quality of
      the studies was good. However, the wide range of tests assessed and the non
      standardised reporting of diagnostic accuracy outcomes meant that statistical
      analysis was not possible. CONCLUSION: Some tests have shown promising results
      for identifying MCI and early dementia. However, concerns over small sample
      sizes, lack of replicability of studies, and lack of evidence available make it
      difficult to make recommendations on the clinical use of the computerised tests
      for diagnosing, monitoring progression, and treatment response for MCI and early
      dementia. Research is required to establish stable cut-off points for automated
      computerised tests used to diagnose patients with MCI or early dementia.

PMID- 29356100
TI  - Layer-specific deformation analysis in severe aortic valve stenosis, primary
      mitral valve regurgitation, and healthy individuals validated against invasive
      hemodynamic measurements of heart function.
AB  - AIM: Speckle tracking echocardiography is considered valuable in assessing left
      ventricular (LV) function. The method has been refined to assess deformation in
      different myocardial layers, but the effect of volume vs pressure overload on
      this pattern is unknown. The aim was to test whether layer-specific myocardial
      strain (LSS) obtained by speckle tracking echocardiography exhibits different
      patterns in conditions with different loading conditions. METHODS AND RESULTS:
      Forty patients with asymptomatic severe aortic stenosis (AS) (AVA 0.81 +/- 0.15
      cm2 , LV ejection fraction [LVEF] 66% +/- 7%), 43 patients with asymptomatic or
      mildly symptomatic significant primary mitral regurgitation (MR) (effective
      regurgitant orifice (ERO) 0.51 (IQR 0.37-0.67) cm2 , LVEF 70% +/- 7%), and 23
      healthy individuals (LVEF 65% +/- 6%) were enrolled. Echocardiography and right
      heart catheterization were performed in all patients. In MR, strain values in
      each myocardial layer (endocardial/global longitudinal strain (GLS)/epicardial)
      were higher (25.0% +/- 3.4%/21.6% +/- 2.9%/18.8% +/- 2.6%) compared to healthy
      individuals (22.6% +/- 3.2%/19.6% +/- 2.9%/17.1% +/- 2.6%) and AS (20.5% +/-
      2.8%/17.7% +/- 2.5%/14.0% +/- 5.6%), P < .001. All 3 groups exhibited a similar
      LSS pattern with highest values in the endocardial and lowest values in the
      epicardial layer. The epicardial-endocardial strain ratio was lower in AS (0.72
      +/- 0.04) than in MR (0.75 +/- 0.04, P = .04). Global longitudinal strain (GLS)
      correlated significantly with LV wall stress (r = .39, P = .0003) but not with LV
      stroke work or contractility. CONCLUSION: Layer-specific myocardial strain (LSS)
      patterns differed in patients with severe AS, significant MR, and healthy
      individuals with highest values in MR. Strain irrespective of layer assessed was
      associated with LV wall stress but seemed less related to contractility and
      unrelated to stroke work in the setting of normal LVEF.

PMID- 29356101
TI  - Eryptosis and hemorheological responses to maximal exercise in athletes:
      Comparison between running and cycling.
AB  - We compared the effects of cycling and running exercise on hemorheological and
      hematological properties, as well as eryptosis markers. Seven endurance-trained
      subjects randomly performed a progressive and maximal exercise test on a cycle
      ergometer and a treadmill. Blood was sampled at rest and at the end of the
      exercise to analyze hematological and blood rheological parameters including
      hematocrit (Hct), red blood cell (RBC) deformability, aggregation, and blood
      viscosity. Hemoglobin saturation (SpO2), blood lactate, and glucose levels were
      also monitored. Red blood cell oxidative stress, calcium content, and
      phosphatidylserine exposure were determined by flow cytometry to assess eryptosis
      level. Cycling exercise increased blood viscosity and RBC aggregation whereas it
      had no significant effect on RBC deformability. In contrast, blood viscosity
      remained unchanged and RBC deformability increased with running. The increase in
      Hct, lactate, and glucose concentrations and the loss of weight at the end of
      exercise were not different between running and cycling. Eryptosis markers were
      not affected by exercise. A significant drop in SpO2 was noted during running but
      not during cycling. Our study showed that a progressive and maximal exercise test
      conducted on a cycle ergometer increased blood viscosity while the same test
      conducted on a treadmill did not change this parameter because of different RBC
      rheological behavior between the 2 tests. We also demonstrated that a short
      maximal exercise does not alter RBC physiology in trained athletes. We suspect
      that exercise-induced hypoxemia occurring during running could be at the origin
      of the RBC rheological behavior differences with cycling.

PMID- 29356102
TI  - Self-assessment of refractive errors using a simple optical approach.
AB  - BACKGROUND: This explorative study investigated procedures for the self
      assessment of spherocylindrical refractive errors. METHODS: Eighteen participants
      with a mean age of 34.0 +/- 8.8 years were enrolled. Adjustable Alvarez lenses
      were mounted in a rotatable ring holder and two procedures were tested for the
      self-adjustment: (1) rotation of the lens in three meridians: 0 degrees , 60
      degrees  and 120 degrees  and (2) rotation of the optotypes in the same
      meridians. Starting from maximum positive power, the participants were required
      to decrease the power of the Alvarez lens until the optotypes (0.0 logMAR)
      appeared to be clear the first time. Best-corrected visual acuity (BVA) was
      measured using a psychophysical staircase procedure. Bland-Altmann analysis was
      carried out in order to calculate the limits of agreement between the self
      refraction method and the standard subjective refraction. RESULTS: Using
      procedure 1, 77 per cent of the subjects achieved a VA >= 0.1 logMAR (6/7.5) and
      the same was true for 88 per cent of the subjects using procedure 2. Using
      procedure 1, a significantly worse BVA was found, when compared to subjective
      refraction (DeltaVA = -0.15 logMAR, F3,140  = 7.11, p = 0.046, median test).
      Analysis of variance (ANOVA) analysis showed a significant influence of the
      refraction method on the oblique astigmatism component J45 but not for the
      spherical equivalent M and the straight astigmatism component J0 (M: F3,140  =
      0.532, p = 0.661; J0 : F3,140  = 0.056, p = 0.983; J45 : F3,140  = 13.97, p <
      0.001; ANOVA). The limits of agreement for the spherical equivalent error M were
      +/- 1.10 D and +/- 1.20 D and for the astigmatic components J0 +/- 0.78 D and +/-
      0.59 D and for J45 +/- 0.62 D and +/- 0.54 D, for procedure 1 and procedure 2,
      respectively. CONCLUSIONS: Fixed adjustable Alvarez lenses and rotatable stimuli
      can provide a fast and precise self-assessment method to measure the
      spherocylindrical error of the eye.

PMID- 29356103
TI  - Analysis of the skin mycobiome in adult patients with atopic dermatitis.
AB  - With the recent availability of culture-independent sequencing methods, studies
      have been conducted to analyse skin micro-organisms present in patients with
      atopic dermatitis (AD). However, the database on the skin fungal communities,
      "mycobiome," has been relatively restrictive compared with the bacterial world.
      We aimed to comparatively analyse the overall skin mycobiome between patients
      with AD and healthy individuals in the Korean population. We analysed skin swab
      samples obtained from the antecubital fossae of 8 patients with AD and 8 healthy
      controls. Using sequencing method followed by direct DNA extraction and molecular
      PCR, taxonomic compositions of fungi at stepwise level ranks were analysed. The
      phylogenic marker used was internal transcribed spacer 2 regions of DNA. We
      observed the tendency of higher intra- and interpersonal taxonomic diversity at
      genus and species levels in AD samples. Non-Malassezia fungal diversity was also
      noticeable in the patient group compared with healthy controls. Malassezia
      globosa and Malassezia restricta were prevalent in all samples across both study
      groups, and some Malassezia species, including Malassezia sloofiae and Malassezia
      dermatis, characterized AD. Our data might provide a new insight into the
      mycobiome of adult AD, which contributes to building a systemic mycobiome
      database in AD.

PMID- 29356105
TI  - Design, synthesis, and evaluation of new alpha-aminonitrile-based benzimidazole
      biomolecules as potent antimicrobial and antitubercular agents.
AB  - The study explores the one-pot synthesis of novel alpha-aminonitriles by reacting
      4-[(1H-benzimidazol-2-yl)methoxy]benzaldehyde, substituted anilines and sodium
      cyanide using a catalytic amount of copper dipyridine dichloride (CuPy2 Cl2 ) and
      employing the Strecker reaction under mild conditions. All the synthesized
      compounds were screened for antimicrobial and antitubercular activity. The
      promising lead compounds 4d and 4e were identified, with MIC values ranging
      between 3.9 and 7.8 ug/mL against different bacterial strains. Compounds 4c-e and
      4g also showed good antifungal activities against the tested fungal strain. Among
      those tested, compound 4e exhibited excellent antitubercular activity (MIC 0.05
      MUg/mL) with a low level of cytotoxicity, suggesting that compound 4e is a
      promising lead for subsequent investigations in search for new antitubercular
      agents.

PMID- 29356106
TI  - Pigmented fungiform lingual papillae: dermoscopic and clinical features.
AB  - The tongue is covered by fungiform, filiform and circumvallate papillae.
      Fungiform papillae may be mainly pigmented in dark-skinned individuals. A single
      centre study aimed to examine the clinical and dermoscopic features of pigmented
      fungiform papulae of the tongue (PFPT) in children, and a concise review of the
      literature has been performed. The clinical and anamnestic data of eight children
      affected by PFPT visited at the Pediatric Dermatology Unit of Bologna between
      2010 and 2017, and a systemic review of all studies of PFPT published on PubMed
      up to 31 August 2017 has been collected and analysed. The results of our data
      were consistent with the literature review: dark brown to black coloured pinhead
      papules or bumps were observed in all cases of PFPT, and three types of clinical
      patterns have been detected. Moreover, the dermoscopic examination showed a
      cobblestone-like distribution and rose petal pattern. PFPT could be associated
      with hyperpigmentation of other sites such as the proximal nail folds and gums,
      and an intrafamiliar transmission is also possible. Clinical and dermoscopic
      features of PFPT may help clinicians to recognize this ethnic, acquired and
      benign condition.

PMID- 29356107
TI  - A Note from the Journal's Editors-in-Chief.

PMID- 29356108
TI  - Polarized transilluminating dermoscopy.

PMID- 29356109
TI  - Congenital sacral mass in a newborn.

PMID- 29356110
TI  - Comment on "Hidradenitis suppurativa in children treated with finasteride-A case
      series".

PMID- 29356112
TI  - A newborn with significant white hyperkeratotic plaques.

PMID- 29356111
TI  - Rapidly spreading subcutaneous nodules in a 2-year-old boy.

PMID- 29356114
TI  - Congenital scalp tumor with ulceration.

PMID- 29356115
TI  - Itchy bumps with new-onset bullae.

PMID- 29356118
TI  - Patient Perspectives: What are hives?

PMID- 29356119
TI  - Asymptomatic bands on an infant's extremity.

PMID- 29356120
TI  - Superexchange Effects on Oxygen Reduction Activity of Edge-Sharing [Cox Mn1-x O6
      ] Octahedra in Spinel Oxide.
AB  - Mn-Co containing spinel oxides are promising, low-cost electrocatalysts for the
      oxygen reduction reaction (ORR). Most studies are devoted to the design of porous
      Mn-Co spinels or to strongly coupled hybrids (e.g., MnCo2 O4 /N-doped-rmGO) to
      maximize the mass efficiency. The lack of analyses by metal oxide intrinsic
      activity (activity normalized to catalysts' surface area) hinders the development
      of fundamental understanding of the physicochemical principles behind the
      catalytic activities. A systematic study on the composition dependence of ORR in
      ZnCox Mn2-x O4 (x = 0.0-2.0) spinel is presented here with special attention to
      the role of edge sharing [Cox Mn1-x O6 ] octahedra in the spinel structure. The
      ORR specific activity of ZnCox Mn2-x O4 spans across a potential window of 200
      mV, indicating an activity difference of ~3 orders of magnitude. The curve of
      composition-dependent ORR specific activity as a function of Co substitution
      exhibits a volcano shape with an optimum Mn/Co ratio of 0.43. It is revealed that
      the modulated eg occupancy of active Mn cations (0.3-0.9), as a consequence of
      the superexchange effect between edge sharing [CoO6 ] and [MnO6 ], reflects the
      ORR activity of edge sharing [Cox Mn1-x O6 ] octahedra in the ZnCox Mn2-x O4
      spinel oxide. These findings offer crucial insights in designing spinel oxide
      catalysts with fine-tuned eg occupancy for efficient catalysis.

PMID- 29356121
TI  - Flow cytometric method for scoring rat liver micronuclei with simultaneous
      assessments of hepatocyte proliferation.
AB  - The current report describes a newly devised method for automatically scoring the
      incidence of rat hepatocyte micronuclei (MNHEP) via flow cytometry, with
      concurrent assessments of hepatocyte proliferation-frequency of Ki-67-positive
      nuclei, and the proportion of polyploid nuclei. Proof-of-concept data are
      provided from experiments performed with 6-week old male Crl:CD(SD) rats exposed
      to diethylnitrosamine (DEN) or quinoline (QUIN) for 3 or 14 consecutive days. Non
      perfused liver tissue was collected 4 days after cessation of treatment in the
      case of 3-day studies, or 1 day after last administration in the case of 14-day
      studies for processing and flow cytometric analysis. In addition to livers, blood
      samples were collected one day after final treatment for micronucleated
      reticulocyte (MN-RET) measurements. Dose-dependent increases in MNHEP, Ki-67
      positive nuclei, and polyploidy were observed in 3- and 14-day DEN studies. Both
      treatment schedules resulted in elevated %MNHEP for QUIN-exposed rats, and while
      cell proliferation effects were subtle, appreciable increases to normalized liver
      weights were observed. Whereas DEN caused markedly higher %MNHEP when exposure
      was extended to two weeks, QUIN-induced MNHEP were slightly increased with
      protracted dosing. Parallel microscopy-based MNHEP frequencies were highly
      correlated with flow cytometry-based measurements (four study/aggregate R2  =
      0.80). No increases in MN-RET were seen in any of the four studies. Collectively,
      these results suggest liver micronuclei are amenable to an automated scoring
      technique that provides objective analyses and higher information content
      relative to conventional microscopy. Additional work is needed to expand the
      number and types of chemicals tested, identify the most advantageous treatment
      schedules, and test the transferability of the method. Environ. Mol. Mutagen.
      59:176-187, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29356122
TI  - Monitoring changes in back fat thickness and its effect on the restoration of
      ovarian activity and fertility in Bos indicus cows.
AB  - With the objective of testing the hypothesis if animals with a stable layer of
      body fat (FAT) during the peripartum have a better chance of becoming pregnant
      after calving, fifty-nine multiparous Brahman cows in their last trimester of
      pregnancy were used. Animals averaged four parturitions and were stocked at a
      rate of 1.25 animal units per hectare and divided into two groups depending on
      the time postpartum (dpp) that the intravaginal releasing device CIDR was
      inserted; Group 1 (<30 dpp; n = 30) received the implant at 25.2 +/- 4.21 and
      withdrawn 9 days later. Group 2 (>=30 dpp; n = 29) received the CIDR at 38.41 +/-
      5.8. Animals were AI at detected oestrus until 170 dpp and calculated as pregnant
      at first service or requiring more than one service (1s and >1s), not pregnant
      but cycling (not pregnant) and those not cycling at all (anestrus). The FAT
      measurements were taken twice each month from the last trimester of gestation
      until 96 dpp. The onset of ovarian activity was monitored through blood levels of
      progesterone (P4) at days 14 and 9 prior to CIDR insertion and days 10, 13, 30
      and 33 after CIDR withdrawal. Animals pregnant did not have any major changes in
      their fat thickness. In contrast, cows pregnant in the group >=30 dpp had changes
      in their FAT homoeostasis, and pregnant animals in the 1s and >1s groups did not
      show differences in dorsal back fat in the last trimester of pregnancy and early
      postpartum. In contrast, animals not pregnant and in anestrus FAT values
      decreased considerably after parturition. Overall, fertility was 49%, but 18% of
      all the animals remained anestrus losing FAT. Thus, animals with adequate
      metabolic conditions will have a better chance of pregnancy regardless of the
      time postpartum when the reproductive programme starts.

PMID- 29356124
TI  - Picosecond alexandrite laser for Naevus of Ota treatment in Chinese.

PMID- 29356123
TI  - Serum Cytokine Profiling in Cats with Acute Idiopathic Cystitis.
AB  - BACKGROUND: Feline idiopathic cystitis (FIC) is a common lower urinary tract
      disorder of domestic cats that resembles interstitial cystitis/painful bladder
      syndrome (IC/PBS) in humans. Diagnosis of FIC is based on clinical signs and
      exclusion of other disorders because of a lack of specific pathologic findings or
      other objective biomarkers. Cytokines are potential noninvasive biomarkers to
      define the presence, severity, and progression of disease, and response to
      treatment. OBJECTIVES: The objective of this pilot study was to determine
      concentrations of selected cytokines in serum from healthy cats and cats with
      acute FIC. ANIMALS: Serum samples from 13 healthy cats and from 12 cats with
      nonobstructive acute FIC were utilized. METHODS: Multiplex analysis of 19
      cytokines (CCL2, CCL5, CXCL1, CXCL12, CXCL8, Flt3L, GM-CSF, IFN-gamma, IL-12
      (p40), IL-13, IL-18, IL-1beta, IL-2, IL-4, IL-6, PDGF-BB, SCF, sFas, and TNF
      alpha) was performed with a commercially available feline-specific multiplex bead
      based assay. RESULTS: Mean serum concentrations of IL-12 (p40; P < 0.0001),
      CXCL12 (P = 0.002), IL-18 (P = 0.032), and Flt3L (P = 0.0024) were significantly
      increased in FIC cats compared to healthy cats. GM-CSF, IL-1b, IL-2, and PDGF-BB
      were undetectable or detected in an insufficient number of cats to allow
      meaningful comparisons. CONCLUSIONS AND CLINICAL IMPORTANCE: We have identified
      increased serum concentrations of pro-inflammatory cytokines and chemokines
      CXCL12, IL-12, IL-18, and Flt3L in FIC-affected cats. These findings suggest
      potential candidates for noninvasive biomarkers for diagnosis, staging, and
      therapeutic outcome monitoring of affected cats and provide additional insight
      into the etiopathogenesis of FIC.

PMID- 29356126
TI  - Acute vascular reaction due to lipo-prostaglandin E1.

PMID- 29356125
TI  - Recent Advances in the Synthesis of Peptoid Macrocycles.
AB  - Over the past two decades, developing medical applications for peptides has, and
      continues to be a highly active area of research. At present there are over 60
      peptide-based drugs on the market and more than 140 in various stages of clinical
      trials. The interest in peptide-based therapeutics arises from their
      biocompatibility and their ability to form defined secondary and tertiary
      structures, resulting in a high selectivity for complex targets. However, there
      are significant challenges associated with the development of peptide-based
      therapeutics, namely peptides are readily metabolised in vivo. Peptoids are an
      emerging class of peptidomimetic and they offer an alternative to peptides.
      Peptoids are comprised of N-substituted glycines where side-chains are located on
      the nitrogen atom of the amide backbone rather than the alpha-carbon as is the
      case in peptides. This change in structure confers a high degree of resistance to
      proteolytic degradation but the absence of any backbone hydrogen bonding means
      that peptoids exhibit a high degree of conformational flexibility. Cyclisation
      has been explored as one possible route to rigidify peptoid structures, making
      them more selective, and, therefore more desirable as potential therapeutics.
      This review outlines the various strategies that have been developed over the
      last decade to access new types of macrocyclic peptoids.

PMID- 29356127
TI  - Parkinson disease with and without Dementia: A prevalence study and future
      projections.
AB  - BACKGROUND: Limited population-based information is available on the co
      occurrence of dementia and PD. However, projecting the prevalence of PD with and
      without dementia during the next 50 years is crucial for planning public-health
      and patient-care initiatives. OBJECTIVES: The objective of this study was to
      project the prevalence of PD with and without dementia in the United States by
      2060. METHODS: We used the Rochester Epidemiology Project medical records-linkage
      system to identify all persons with PD with or without dementia residing in
      Olmsted County, Minnesota, on January 1, 2006. A movement disorders specialist
      reviewed the complete medical records of each person to confirm the presence of
      PD. We calculated the age- and sex-specific prevalence of PD with and without
      dementia and projected U.S. prevalence through 2060. RESULTS: We identified 296
      persons with PD with and without dementia on the prevalence date (187 men, 109
      women); the overall prevalence increased with age from 0.01% (30-39 years) to
      2.83% (>=90 years). The prevalence of PD without dementia increased with age from
      0.01% (30-39 years) to 1.25% (>=90 years). The prevalence of PD with dementia
      increased with age from 0.10% (60-69 years) to 1.59% (>=90 years). The prevalence
      was higher in men than in women for all subtypes and all age groups. We project
      by 2060 an approximate doubling of the number of persons with PD without dementia
      and a tripling of the number of persons with PD with dementia in the United
      States. CONCLUSIONS: The prevalence of PD with and without dementia increases
      with age and is higher in men than women. We project that the number of persons
      with PD in the United States will increase substantially by 2060. (c) 2018
      International Parkinson and Movement Disorder Society.

PMID- 29356128
TI  - Clay-Inspired MXene-Based Electrochemical Devices and Photo-Electrocatalyst:
      State-of-the-Art Progresses and Challenges.
AB  - MXene, an important and increasingly popular category of postgraphene 2D
      nanomaterials, has been rigorously investigated since early 2011 because of
      advantages including flexible tunability in element composition, hydrophobicity,
      metallic nature, unique in-plane anisotropic structure, high charge-carrier
      mobility, tunable band gap, and favorable optical and mechanical properties. To
      fully exploit these potentials and further expand beyond the existing boundaries,
      novel functional nanostructures spanning monolayer, multilayer, nanoparticles,
      and composites have been developed by means of intercalation, delamination,
      functionalization, hybridization, among others. Undeniably, the cutting-edge
      developments and applications of clay-inspired 2D MXene platform as
      electrochemical electrode or photo-electrocatalyst have conferred superior
      performance and have made significant impact in the field of energy and advanced
      catalysis. This review provides an overview of the fundamental properties and
      synthesis routes of pure MXene, functionalized MXene and their hybrids,
      highlights the state-of-the-art progresses of MXene-based applications with
      respect to supercapacitors, batteries, electrocatalysis and photocatalysis, and
      presents the challenges and prospects in the burgeoning field.

PMID- 29356129
TI  - Large-Area Direct Laser-Shock Imprinting of a 3D Biomimic Hierarchical Metal
      Surface for Triboelectric Nanogenerators.
AB  - Ongoing efforts in triboelectric nanogenerators (TENGs) focus on enhancing power
      generation, but obstacles concerning the economical and cost-effective production
      of TENGs continue to prevail. Micro-/nanostructure engineering of polymer
      surfaces has been dominantly utilized for boosting the contact
      triboelectrification, with deposited metal electrodes for collecting the
      scavenged energy. Nevertheless, this state-of-the-art approach is limited by the
      vague potential for producing 3D hierarchical surface structures with conformable
      coverage of high-quality metal. Laser-shock imprinting (LSI) is emerging as a
      potentially scalable approach for directly surface patterning of a wide range of
      metals with 3D nanoscale structures by design, benefiting from the ultrahigh
      strain-rate forming process. Here, a TENG device is demonstrated with LSI
      processed biomimetic hierarchically structured metal electrodes for efficient
      harvesting of water-drop energy in the environment. Mimicking and transferring
      hierarchical microstructures from natural templates, such as leaves, into these
      water-TENG devices is effective regarding repelling water drops from the device
      surface, since surface hydrophobicity from these biomicrostructures maximizes the
      TENG output. Among various leaves' microstructures, hierarchical microstructures
      from dried bamboo leaves are preferable regarding maximizing power output, which
      is attributed to their unique structures, containing both dense nanostructures
      and microscale features, compared with other types of leaves. Also, the
      triboelectric output is significantly improved by closely mimicking the
      hydrophobic nature of the leaves in the LSI-processed metal surface after
      functionalizing it with low-surface-energy self-assembled-monolayers. The
      approach opens doors to new manufacturable TENG technologies for economically
      feasible and ecologically friendly production of functional devices with directly
      patterned 3D biomimic metallic surfaces in energy, electronics, and sensor
      applications.

PMID- 29356130
TI  - High-Strength Nanotwinned Al Alloys with 9R Phase.
AB  - Light-weight aluminum (Al) alloys have widespread applications. However, most Al
      alloys have inherently low mechanical strength. Nanotwins can induce high
      strength and ductility in metallic materials. Yet, introducing high-density
      growth twins into Al remains difficult due to its ultrahigh stacking-fault
      energy. In this study, it is shown that incorporating merely several atomic
      percent of Fe solutes into Al enables the formation of nanotwinned (nt) columnar
      grains with high-density 9R phase in Al(Fe) solid solutions. The nt Al-Fe alloy
      coatings reach a maximum hardness of ~5.5 GPa, one of the strongest binary Al
      alloys ever created. In situ uniaxial compressions show that the nt Al-Fe alloys
      populated with 9R phase have flow stress exceeding 1.5 GPa, comparable to high
      strength steels. Molecular dynamics simulations reveal that high strength and
      hardening ability of Al-Fe alloys arise mainly from the high-density 9R phase and
      nanoscale grain sizes.

PMID- 29356132
TI  - Participatory development of incentives to coexist with jaguars and pumas.
AB  - Reducing costs and increasing benefits for rural communities coexisting with
      large carnivores is necessary for conservation of jaguar (Panthera onca) and puma
      (Puma concolor). To design acceptable incentives, stakeholders must be involved
      in the process. We conducted an innovative, structured, group communication
      process based on a Delphi technique as a template for identifying potential
      incentives. Community workshops with 133 members of 7 communities and surveys
      with 25 multidisciplinary experts from government, nongovernmental organizations,
      and academia provided iterative data to design a plan of incentives through 4
      rounds of discussion. The final product integrated 862 ideas into 6 types of
      incentives: organization of communities, mechanisms for improved dialogue,
      citizen technical assistance, green labeling for community products, payment for
      the ecosystem service of biodiversity, and an assessment of financial
      alternatives. We used quantitative and qualitative techniques to indicate support
      for decisions about the design of incentives, which reduced researcher
      subjectivity. The diverse incentives developed and the cooperation from multiple
      stakeholders resulted in an incentive plan that integrated issues of governance,
      equity, and social norms.

PMID- 29356131
TI  - Copper-Catalyzed Aziridination with Redox-Active Ligands: Molecular Spin
      Catalysis.
AB  - Small-molecule catalysts as mimics of biological systems illustrate the chemists'
      attempts at emulating the tantalizing abilities displayed by nature's
      metalloenzymes. Among these innate behaviors, spin multistate reactivity is used
      by biological systems as it offers thermodynamic leverage towards challenging
      chemical reactivity but this concept is difficult to translate into the realm of
      synthetic organometallic catalysis. Here, we report a rare example of molecular
      spin catalysis involving multistate reactivity in a small-molecule biomimetic
      copper catalyst applied to aziridination. This behavior is supported by spin
      state flexibility enabled by the redox-active ligand.

PMID- 29356133
TI  - Motor cortex synchronization influences the rhythm of motor performance in
      premanifest huntington's disease.
AB  - BACKGROUND: In Huntington's disease there is evidence of structural damage in the
      motor system, but it is still unclear how to link this to the behavioral disorder
      of movement. One feature of choreic movement is variable timing and coordination
      between sequences of actions. We postulate this results from desynchronization of
      neural activity in cortical motor areas. OBJECTIVES: The objective of this study
      was to explore the ability to synchronize activity in a motor network using
      transcranial magnetic stimulation and to relate this to timing of motor
      performance. METHODS: We examined synchronization in oscillatory activity of
      cortical motor areas in response to an external input produced by a pulse of
      transcranial magnetic stimulation. We combined this with EEG to compare the
      response of 16 presymptomatic Huntington's disease participants with 16 age
      matched healthy volunteers to test whether the strength of synchronization
      relates to the variability of motor performance at the following 2 tasks: a grip
      force task and a speeded-tapping task. RESULTS: Phase synchronization in response
      to M1 stimulation was lower in Huntington's disease than healthy volunteers (P <
      .01), resulting in a reduced cortical activity at global (P < .02) and local
      levels (P < .01). Participants who showed better timed motor performance also
      showed stronger oscillatory synchronization (r = -0.356; P < .05) and higher
      cortical activity (r = -0.393; P < .05). CONCLUSIONS: Our data may model the
      ability of the motor command to respond to more subtle, physiological inputs from
      other brain areas. This novel insight indicates that impairments of the timing
      accuracy of synchronization and desynchronization could be a physiological basis
      for some key clinical features of Huntington's disease. (c) 2018 International
      Parkinson and Movement Disorder Society.

PMID- 29356134
TI  - Morphology, morphometry and chromatin distribution in llama sperm nuclei.
AB  - The objectives of this study were as follows: (i) to describe and evaluate the
      frequencies of different morphologies of llama sperm nuclei, (ii) to determine
      morphometric values of nuclear parameters, (iii) to describe and estimate the
      frequencies of different classes of chromatin distribution and (iv) to measure
      haploid DNA content and analyse its nuclear distribution. The study was performed
      using ejaculates collected from seven males, and sperm nuclei were stained with
      the Feulgen reaction. Normal morphology ranged from 78.36% to 93.92%, and
      abnormalities included short, small, large, pyriform, narrow, micro and round
      nuclei. Important differences in nuclei considered normal were found between some
      males. The following average values were obtained for each sperm nuclear
      morphometric parameter analysed: area 11.64 MUm2 , perimeter 13.16 MUm, length
      5.12 MUm, width 2.81 MUm, ellipticity 1.85 and form 0.83. Differences between
      males were significant for all the parameters (p < .01). Light microscope
      observations and cytophotometric determinations allowed discriminating between
      three classes of chromatin distribution: homogeneous, diffuse and showing a clear
      band. Significant differences between males were found for the frequencies of the
      three classes (p < .01). Cluster analysis methods were used to estimate the
      resemblance between males according to the characteristics of their sperm nuclei.
      A great intermale variability was found for morphological, morphometric and
      chromatin distribution data. These parameters would have low dependence between
      them.

PMID- 29356135
TI  - Neurogenic bladder in progressive supranuclear palsy: A comparison with
      Parkinson's disease and multiple system atrophy.
AB  - AIMS: Progressive supranuclear palsy (PSP) can present urinary symptoms, similar
      to other parkinsonian disorders. We investigated the urodynamic parameters of PSP
      and compared them with those of idiopathic Parkinson's disease (IPD) and multiple
      system atrophy (MSA) METHODS: We retrospectively analyzed the urodynamic data in
      patients diagnosed with parkinsonian disorders (PSP, IPD, and MSA) presenting
      urinary symptoms. Clinical data, including onset age, duration, and severity, as
      well as treatment status of parkinsonian disorders and urinary symptoms were
      collected. RESULTS: A total of 131 patients (10 with PSP, 79 with IPD, and 42
      with MSA) were included. The mean age and disease onset age of PSP patients were
      similar to those of IPD patients, but older than those of MSA patients. The
      disease duration until the onset of urinary symptoms in PSP patients was similar
      to that in MSA patients, but shorter than that in IPD patients. According to the
      urodynamic study, storage phase dysfunctions in PSP patients were similar to
      those in IPD or MSA patients. However, according to a pressure-flow study, PSP
      patients showed higher rates of voiding failure, as well as lower maximum flow
      rate, higher post-void residual volume, and higher proportions of impaired
      detrusor contraction than IPD patients, but rather similar to MSA patients.
      CONCLUSIONS: Urinary dysfunctions in PSP patients were as extensive as those with
      MSA, and were more severe than those with IPD, especially in the voiding phase.
      This may reflect the extensive degenerative process of neural structure in PSP
      patients.

PMID- 29356136
TI  - Effects of uncertainty and variability on population declines and IUCN Red List
      classifications.
AB  - The International Union for Conservation of Nature (IUCN) Red List Categories and
      Criteria is a quantitative framework for classifying species according to
      extinction risk. Population models may be used to estimate extinction risk or
      population declines. Uncertainty and variability arise in threat classifications
      through measurement and process error in empirical data and uncertainty in the
      models used to estimate extinction risk and population declines. Furthermore,
      species traits are known to affect extinction risk. We investigated the effects
      of measurement and process error, model type, population growth rate, and age at
      first reproduction on the reliability of risk classifications based on projected
      population declines on IUCN Red List classifications. We used an age-structured
      population model to simulate true population trajectories with different growth
      rates, reproductive ages and levels of variation, and subjected them to
      measurement error. We evaluated the ability of scalar and matrix models
      parameterized with these simulated time series to accurately capture the IUCN Red
      List classification generated with true population declines. Under all levels of
      measurement error tested and low process error, classifications were reasonably
      accurate; scalar and matrix models yielded roughly the same rate of
      misclassifications, but the distribution of errors differed; matrix models led to
      greater overestimation of extinction risk than underestimations; process error
      tended to contribute to misclassifications to a greater extent than measurement
      error; and more misclassifications occurred for fast, rather than slow, life
      histories. These results indicate that classifications of highly threatened taxa
      (i.e., taxa with low growth rates) under criterion A are more likely to be
      reliable than for less threatened taxa when assessed with population models.
      Greater scrutiny needs to be placed on data used to parameterize population
      models for species with high growth rates, particularly when available evidence
      indicates a potential transition to higher risk categories.

PMID- 29356137
TI  - Selective P-C(sp3 ) Bond Cleavage and Radical Alkynylation of alpha-Phosphorus
      Alcohols by Photoredox Catalysis.
AB  - Herein the first P-C(sp3 ) bond cleavage and radical alkynylation of alpha
      phosphorus alcohols to construct phosphonoalkynes is reported. The phosphorus
      radical is generated upon P-C bond cleavage reaction via the alkoxyl radical
      through photoredox catalysis with cyclic iodine(III) reagents. Various
      arylphosphinoyl-, alkylphosphinoyl-, phosphonate-, and phosphonic amide alcohols
      serve as radical phosphorus precursors to construct phosphonoalkynes for the
      first time.

PMID- 29356138
TI  - Seasonal changes in epidermal ceramides are linked to impaired barrier function
      in acne patients.
AB  - Acne skin demonstrates increased transepidermal water loss (TEWL) compared with
      healthy skin, which may be due, in part, to altered ceramide (CER) levels. We
      analysed ceramides in the stratum corneum of healthy and acne skin, and studied
      seasonal variation over the course of a year. Using ultraperformance liquid
      chromatography with electrospray ionisation and tandem mass spectrometry
      (UPLC/ESI-MS/MS), we identified 283 ceramides. Acne-affected skin demonstrated
      overall lower levels of ceramides, with notable reductions in CER[NH] and CER[AH]
      ceramides, as well as the acylceramides CER[EOS] and CER[EOH]; these differences
      were more apparent in the winter months. Lower ceramide levels reflected an
      increase in TEWL in acne, compared with healthy skin, which partly resolves in
      the summer. Individual ceramide species with 18-carbon 6-hydroxysphingosine (H)
      bases (including CER[N(24)H(18)], CER[N(26)H(18)], CER[A(24)H(18)],
      CER[A(26)H(18)]) were significantly reduced in acne skin, suggesting that CER[NH]
      and CER[AH] species may be particularly important in a healthy skin barrier.

PMID- 29356139
TI  - Rates of Chemical Reactions Embedded in a Metabolic Network by Dissolution
      Dynamic Nuclear Polarisation NMR.
AB  - The isomerisation of 6-phosphogluconolactones and their hydrolyses into 6
      phosphogluconic acid form a non enzymatic side cycle of the pentose-phosphate
      pathway (PPP) in cells. Dissolution dynamic nuclear polarisation can be used for
      determining the kinetic rates of the involved transformations in real time. It is
      found that the hydrolysis of both lactones is significantly slower than the
      isomerisation process, thereby shedding new light onto this subtle chemical
      process.

PMID- 29356140
TI  - Clinicopathological features and course of cutaneous protothecosis.
AB  - BACKGROUND: Protothecosis is an uncommon infection caused by the achlorophyllic
      algae found more commonly in tropical areas. Only a limited number of cases have
      been reported. OBJECTIVE: We aimed to evaluate the clinicopathological features
      and treatment outcomes of cutaneous protothecosis. METHODS: We retrospectively
      identified 20 pathology-confirmed cases of cutaneous protothecosis based on skin
      biopsies in two tertiary medical centres in Taiwan from 1997 to 2015. RESULTS:
      The age of the patients at the time of diagnosis ranged from 48 to 85 years (mean
      age of 74 years). All lesions developed on the limbs. Twelve (60%) patients had
      adrenal insufficiency, but no patients had active malignancy at diagnosis.
      Interestingly, four (20%) patients had concurrent scabies infestation.
      Clinically, most lesions were erythematous plaques studded with punctate ulcers.
      Microscopically, the most common finding was granulomatous inflammation. Nineteen
      (95%) cases were successfully treated with itraconazole for 14-148 days with only
      one case of recurrence. Concomitant scabies should be suspected if pruritus is
      recalcitrant despite itraconazole treatment. CONCLUSION: Despite its rarity,
      cutaneous protothecosis has become more significant due to an increased
      prevalence of immunocompromised individuals. Steroid overuse or iatrogenic
      adrenal insufficiency predisposes individuals to high-risk infections. Neglecting
      the disease leads to a chronic and incurable state. Protothecosis should be
      suspected in chronic eczematous and ulcerative plaques on the limbs refractory to
      conventional antibacterial and antiviral treatments, especially in patients with
      adrenal insufficiency. Clinical suspicion should be confirmed by skin biopsies,
      and confirmed cases can be successfully treated with itraconazole.

PMID- 29356141
TI  - Stable Molecular Diodes Based on pi-pi Interactions of the Molecular Frontier
      Orbitals with Graphene Electrodes.
AB  - In molecular electronics, it is important to control the strength of the molecule
      electrode interaction to balance the trade-off between electronic coupling
      strength and broadening of the molecular frontier orbitals: too strong coupling
      results in severe broadening of the molecular orbitals while the molecular
      orbitals cannot follow the changes in the Fermi levels under applied bias when
      the coupling is too weak. Here, a platform based on graphene bottom electrodes to
      which molecules can bind via pi-pi interactions is reported. These interactions
      are strong enough to induce electronic function (rectification) while minimizing
      broadening of the molecular frontier orbitals. Molecular tunnel junctions are
      fabricated based on self-assembled monolayers (SAMs) of Fc(CH2 )11 X (Fc =
      ferrocenyl, X = NH2 , Br, or H) on graphene bottom electrodes contacted to
      eutectic alloy of gallium and indium top electrodes. The Fc units interact more
      strongly with graphene than the X units resulting in SAMs with the Fc at the
      bottom of the SAM. The molecular diodes perform well with rectification ratios of
      30-40, and they are stable against bias stressing under ambient conditions. Thus,
      tunnel junctions based on graphene with pi-pi molecule-electrode coupling are
      promising platforms to fabricate stable and well-performing molecular diodes.

PMID- 29356142
TI  - Engineering On-Surface Spin Crossover: Spin-State Switching in a Self-Assembled
      Film of Vacuum-Sublimable Functional Molecule.
AB  - The realization of spin-crossover (SCO)-based applications requires study of the
      spin-state switching characteristics of SCO complex molecules within
      nanostructured environments, especially on surfaces. Except for a very few cases,
      the SCO of a surface-bound thin molecular film is either quenched or heavily
      altered due to: (i) molecule-surface interactions and (ii) differing
      intermolecular interactions in films relative to the bulk. By fabricating SCO
      complexes on a weakly interacting surface, the interfacial quenching problem is
      tackled. However, engineering intermolecular interactions in thin SCO active
      films is rather difficult. Here, a molecular self-assembly strategy is proposed
      to fabricate thin spin-switchable surface-bound films with programmable
      intermolecular interactions. Molecular engineering of the parent complex system
      [Fe(H2 B(pz)2 )2 (bpy)] (pz = pyrazole, bpy = 2,2'-bipyridine) with a dodecyl
      (C12 ) alkyl chain yields a classical amphiphile-like functional and vacuum
      sublimable charge-neutral FeII complex, [Fe(H2 B(pz)2 )2 (C12 -bpy)] (C12 -bpy =
      dodecyl[2,2'-bipyridine]-5-carboxylate). Both the bulk powder and 10 nm thin
      films sublimed onto either quartz glass or SiOx surfaces of the complex show
      comparable spin-state switching characteristics mediated by similar lamellar
      bilayer like self-assembly/molecular interactions. This unprecedented observation
      augurs well for the development of SCO-based applications, especially in
      molecular spintronics.

PMID- 29356143
TI  - Alterations in glucose concentrations affect DNA methylation at Lrg1 in an ex
      vivo rat cortical slice model of preterm brain injury.
AB  - Preterm birth affects 5-18% of all babies and is associated with
      neurodevelopmental impairment and increased neuropsychiatric disease risk.
      Although preterm birth associates with differential DNA methylation at
      neurodevelopmental genes in buccal DNA, including leucine-rich alpha-2
      glycoprotein 1 (LRG1), it is not known whether these differences also occur in
      the brain, or whether they persist. Thus, there is a need for animal models or in
      vitro systems in which to undertake longitudinal and mechanistic studies. We used
      a combination of in vivo rat studies and ex vivo experiments in rat cortical
      slices to explore their utility in modelling the human preterm brain. We
      identified temporal changes in DNA methylation at LRG1 in human buccal DNA over
      the first year of life and found persistent differences in LRG1 methylation
      between preterm and term infants at 1 year. These developmental changes also
      occurred in rat brains in vivo, alongside changes in global DNA
      hydroxymethylation and expression of the ten-eleven translocation (Tet1) enzyme,
      and were reproducible in ex vivo rat cortical slices. On the basis of the
      observation that neonatal glucose homeostasis can modify neurodevelopmental
      outcome, we studied whether glucose concentration affects Lrg1 methylation using
      cortical slices. Culture of slices in lower glucose concentration was associated
      with lower Lrg1 methylation, lower global 5hmC and Tet1 expression. Our results
      suggest that ex vivo organotypic cultures may be useful in the study of
      biological and environmental influences on the epigenome and that perturbations
      during early life including glucose concentration can affect methylation at
      specific genes implicated in neurodevelopment.

PMID- 29356144
TI  - Beneficial effects of oleuropein on glucose uptake and on parameters relevant to
      the normal homeostatic mechanisms of glucose regulation in rat skeletal muscle.
AB  - Oleuropein, the main constituents of leaves and fruits of the olive tree, has
      been demonstrated to exert various therapeutic and pharmacological properties
      including antidiabetic effect. However, the effectiveness of oleuropein on
      glucose homeostasis in intact rat skeletal muscle ex vivo has never been
      explored. Therefore, our current study was carried out to investigate and confirm
      the beneficial effect of oleuropein (1.5 mM) on glucose uptake and on parameters
      relevant to the normal homeostatic mechanisms of glucose regulation in rat
      skeletal muscle. For this purpose, soleus muscles were incubated for 12 hr
      without (control) or with oleuropein, in the presence or absence of AMP-activated
      protein kinase (AMPK) inhibitor, compound C, or wortmannin, an inhibitor of
      phosphatidylinositol kinase. Oleuropein-stimulated glucose transport,
      plasmalemmal glucose transporter 4 (GLUT4), and phosphorylation of
      phosphatidylinositol kinase and AMPK were examined. We observed that oleuropein
      treatment enhanced glucose transport, GLUT4 translocation, and AMPK
      phosphorylation. The oleuropein-stimulated glucose uptake and GLUT4 translocation
      were inhibited by compound C and were not affected by wortmannin. These results
      suggest that increased glucose uptake induced by oleuropein might be mediated
      through activation of AMPK and the subsequent increase in GLUT4 translocation in
      skeletal muscles.

PMID- 29356145
TI  - Exploring Anomalous Polarization Dynamics in Organometallic Halide Perovskites.
AB  - Organometallic halide perovskites (OMHPs) have attracted broad attention as
      prospective materials for optoelectronic applications. Among the many anomalous
      properties of these materials, of special interest are the ferroelectric
      properties including both classical and relaxor-like components, as a potential
      origin of slow dynamics, field enhancement, and anomalous mobilities. Here,
      ferroelectric properties of the three representative OMHPs are explored,
      including FAPbx Sn1-x I3 (x = 0, x = 0.85) and FA0.85 MA0.15 PbI3 using band
      excitation piezoresponse force microscopy and contact mode Kelvin probe force
      microscopy, providing insight into long- and short-range dipole and charge
      dynamics in these materials and probing ferroelectric density of states.
      Furthermore, second-harmonic generation in thin films of OMHPs is observed,
      providing a direct information on the noncentrosymmetric polarization in such
      materials. Overall, the data provide strong evidence for the presence of
      ferroelectric domains in these systems; however, the domain dynamics is
      suppressed by fast ion dynamics. These materials hence present the limit of
      ferroelectric materials with spontaneous polarization dynamically screened by
      ionic and electronic carriers.

PMID- 29356146
TI  - Bioinspired Underwater Adhesives by Using the Supramolecular Toolbox.
AB  - Nature has developed protein-based adhesives whose underwater performance has
      attracted much research attention over the last few decades. The adhesive
      proteins are rich in catechols combined with amphiphilic and ionic features. This
      combination of features constitutes a supramolecular toolbox, to provide stimuli
      responsive processing of the adhesive, to secure strong adhesion to a variety of
      surfaces, and to control the cohesive properties of the material. Here, the
      versatile interactions used in adhesives secreted by sandcastle worms and mussels
      are explored. These biological principles are then put in a broader perspective,
      and synthetic adhesive systems that are based on different types of
      supramolecular interactions are summarized. The variety and combinations of
      interactions that can be used in the design of new adhesive systems are
      highlighted.

PMID- 29356148
TI  - Oxygen Evolution Activity of Co-Ni Nanochain Alloys: Promotion by Electron
      Injection.
AB  - Metal alloy nanoparticles have shown promising applications in electrocatalysis.
      However, the nanoparticles usually suffer from limited charge-transfer
      efficiency, which can be solved by preparing one-dimensional materials. Herein,
      Co-Ni alloy nanochains are prepared by a direct-current arc-discharge method. The
      nanochains, comprised of mutually coupled uniform nanospheres, can range up to
      several micrometers in size. When the alloy is exposed to air or under the
      electro-oxidation process, a metal-metal-oxide heterostructure is obtained. The
      alloy can inject electrons into the oxide, which makes it more suitable for
      electrocatalysis. The composition of the samples can be changed by varying the
      ratio of Ni/Co (i.e., Co, Co7 Ni3 , Co5 Ni5 , Co3 Ni7 , Ni) in the synthesis
      process. The nanochains show good oxygen evolution performance that correlates
      with the Ni/Co ratio. Co7 Ni3 demonstrates optimal activity with an onset point
      of 1.50 V vs. reversible hydrogen electrode (RHE) and overpotential of 350 mV at
      10 mA cm-2 . The alloy nanochains also show excellent durability with 95.0 %
      current retention after a long-term test for 12 h.

PMID- 29356147
TI  - Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner
      preference and anxiety in male mice.
AB  - The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain
      involved in regulating emotional and sexual behaviours. There is, however,
      limited information available on the specific neuronal cell type in the MePD
      functionally mediating these behaviours in rodents. The recent discovery of a
      significant kisspeptin neurone population in the MePD has raised interest in the
      possible role of kisspeptin and its cognate receptor in sexual behaviour. The
      present study therefore tested the hypothesis that the MePD kisspeptin neurone
      population is involved in regulating attraction towards opposite sex
      conspecifics, sexual behaviour, social interaction and the anxiety response by
      selectively stimulating these neurones using the novel pharmacosynthetic DREADDs
      (designer receptors exclusively activated by designer drugs) technique. Adult
      male Kiss-Cre mice received bilateral stereotaxic injections of a stimulatory
      DREADD viral construct (AAV-hSyn-DIO-hM3 D(Gq)-mCherry) targeted to the MePD,
      with subsequent activation by i.p. injection of clozapine-N-oxide (CNO). Socio
      sexual behaviours were assessed in a counter-balanced fashion after i.p.
      injection of either saline or CNO (5 mg kg-1 ). Selective activation of MePD
      kisspeptin neurones by CNO significantly increased the time spent by male mice in
      investigating an oestrous female, as well as the duration of social interaction.
      Additionally, after CNO injection, the mice appeared less anxious, as indicated
      by a longer exploratory time in the open arms of the elevated plus maze. However,
      levels of copulatory behaviour were comparable between CNO and saline-treated
      controls. These data indicate that DREADD-induced activation of MePD kisspeptin
      neurones enhances both sexual partner preference in males and social interaction
      and also decreases anxiety, suggesting a key role played by MePD kisspeptin in
      sexual motivation and social behaviour.

PMID- 29356149
TI  - A multicenter, prospective, observational study examining the impact of risk
      factors, such as BMI and waist circumference, on quality of life improvement and
      clinical response in moderate-to-severe plaque-type psoriasis patients treated
      with infliximab in routine care settings of Greece.
AB  - BACKGROUND: Obesity has been associated with moderate-to-severe plaque psoriasis
      severity and PASI 75 response attainment of biologic therapies, but findings are
      inconsistent. OBJECTIVE: This study aimed to examine the association of body mass
      index (BMI) and waist circumference (WC) on disease severity, to identify
      potential patient characteristics associated with response attainment and to
      assess the impact of infliximab on the patients' health-related quality of life
      (HRQoL) among infliximab-treated patients in the routine care setting of Greece.
      METHODS: This was a multicenter, prospective, observational study of adult
      moderate-to-severe plaque psoriasis patients who had initiated treatment with
      originator infliximab within 2 weeks prior to enrolment. Postenrolment visits
      occurred at 14 +/- 4, 30 +/- 4 and 54 +/- 4 weeks following treatment onset.
      RESULTS: Between October 2012 and June 2014, 136 eligible patients (62.5% males)
      with a median age of 48.6 years, BMI of 29.6 kg/m2 and WC of 107.0 cm at
      enrolment were recruited by 21 dermatology hospital/private offices. All patients
      had received prior psoriasis treatment(s); 62.5% were biologic-naive. Mean
      baseline psoriasis area severity index (PASI) and Dermatology Quality of Life
      Index (DLQI) scores were 23.4 +/- 13.6 and 15.0 +/- 8.3, respectively. A low
      correlation was observed between WC at enrolment and baseline PASI [rho = 0.324
      (P < 0.001)]. Over a median 48.4 weeks of infliximab exposure, 89.3% of the per
      protocol set achieved a PASI 75 response. At 14, 30 and 54 weeks, the PASI 75
      attainment rate was 66.4%, 74.8% and 76.6%, respectively; the clinically
      meaningful DLQI improvement (>=5 point decrease) rate was 68.9%, 75.7% and 69.8%,
      respectively. BMI category and abdominal obesity at enrolment did not impact PASI
      75 or DLQI improvement rate attainment. CONCLUSION: In the routine care of
      Greece, infliximab reduced disease activity and improved the quality of life of
      moderate-to-severe psoriasis patients through 1 year of treatment, independent of
      their BMI and WC.

PMID- 29356150
TI  - Skin-Inspired Multifunctional Autonomic-Intrinsic Conductive Self-Healing
      Hydrogels with Pressure Sensitivity, Stretchability, and 3D Printability.

PMID- 29356151
TI  - Recent Advances in Germanium-Based Photoinitiator Chemistry.
AB  - Acylgermanes provide an outstanding photoinduced reactivity at very useful
      absorption wavelengths. This encouraged multidisciplinary research groups to
      utilize them as highly effective and non-toxic photoinitiators particularly for
      medical applications. In this Minireview, we present the most recent
      breakthroughs to synthesize acylgermanes. We also outline mechanistic aspects of
      photoinduced reactions of several acylgermane derivatives based on fundamental
      spectroscopic insights. These studies may aid future developments for tailor-made
      photoinitiators.

PMID- 29356152
TI  - A tango for two: Dopamine and alpha-synuclein synergy may explain nigrostriatal
      degeneration in Parkinson's disease.

PMID- 29356153
TI  - MUN (MERISTEM UNSTRUCTURED), encoding a SPC24 homolog of NDC80 kinetochore
      complex, affects development through cell division in Arabidopsis thaliana.
AB  - Kinetochore, a protein super-complex on the centromere of chromosomes, mediates
      chromosome segregation during cell division by providing attachment sites for
      spindle microtubules. The NDC80 complex, composed of four proteins, NDC80, NUF2,
      SPC24 and SPC25, is localized at the outer kinetochore and connects spindle
      fibers to the kinetochore. Although it is conserved across species, functional
      studies of this complex are rare in Arabidopsis. Here, we characterize a
      recessive mutant, meristem unstructured-1 (mun-1), exhibiting an abnormal
      phenotype with unstructured shoot apical meristem caused by ectopic expression of
      the WUSCHEL gene in unexpected tissues. mun-1 is a weak allele because of the
      insertion of T-DNA in the promoter region of the SPC24 homolog. The mutant
      exhibits stunted growth, embryo arrest, DNA aneuploidy, and defects in chromosome
      segregation with a low cell division rate. Null mutants of MUN from TALEN and
      CRISPR/Cas9-mediated mutagenesis showed zygotic embryonic lethality similar to
      nuf2-1; however, the null mutations were fully transmissible via pollen and
      ovules. Interactions among the components of the NDC80 complex were confirmed in
      a yeast two-hybrid assay and in planta co-immunoprecipitation. MUN is co
      localized at the centromere with HTR12/CENH3, which is a centromere-specific
      histone variant, but MUN is not required to recruit HTR12/CENH3 to the
      kinetochore. Our results support that MUN is a functional homolog of SPC24 in
      Arabidopsis, which is required for proper cell division. In addition, we report
      the ectopic generations of stem cell niches by the malfunction of kinetochore
      components.

PMID- 29356154
TI  - Encoding, Reading, and Transforming Information Using Multifluorescent
      Supramolecular Polymeric Hydrogels.
AB  - Traditional (1D, 2D, and 3D) codes are widely used to provide convenient readouts
      of encoded information. However, manipulating and transforming the encoded
      information is typically difficult to achieve. Here, the preparation of three
      fluorescent (blue, green, and red) hydrogels containing both tetracationic
      receptor-anion recognition motifs and gel-specific fluorophores is reported,
      which may be used as building blocks to construct through physical adhesion
      fluorescent color 3D codes (Code A, Code B, and Code C) that may be read out by a
      smartphone. As a result, parts of the individual gel components that make up Code
      B can be replaced with other gel building blocks to form Code A via a cut and
      adhesion approach. A fluorophore responsive to ammonia is further incorporated
      into one of the hydrogels. This allows the gel block-derived pattern that makes
      up Code C to be converted to Code A by chemical means. Therefore, the encoded
      information produced by patterns of the present hydrogels may be transformed
      through either physical action or by exposure to a chemical stimulus. Due to the
      nature of the soft materials involved, the codes can be used as wearable
      materials.

PMID- 29356156
TI  - Dynamic Polymorph Formation during Evaporative Crystallization from Solution: The
      Key Role of Liquid-Like Clusters as "Crucible" at Ambient Temperature.
AB  - Understanding the polymorph phenomenon for organic crystals is essential for the
      development of organic solid materials. Here, the fluorescence study of the
      evaporative crystallization of 1,3-dipyrrol-2-yl-1,3-propanedione boron
      difluoride complex (1), which has three polymorphs showing different emission
      profiles, is reported. The droplet of 1 in 1,2-dichloroethane showed blue
      emission just after dropping. Solids with bluish-green emission were observed. As
      time elapsed, a solid with red or orange emission was observed around the
      droplet. Time evolution of the fluorescence spectra, observed for the first time,
      implied that the molten state of 1 was observed by emission of an intermediate,
      even at ambient temperature. These findings suggested that the liquid-like
      cluster incidentally forms an ordered array as the crystallites nucleate. The
      liquid-like cluster can be considered as the "crucible" in the nucleation of
      polymorphs.

PMID- 29356155
TI  - Metabolic Study of Dioecy in Mauritia flexuosa: NMR-based and Chemometric
      Approaches.
AB  - INTRODUCTION: Mauritia flexuosa is a dioecious species native to the Amazon, and
      the gender identification can currently be determined through the differentiation
      between female and male flowers in the first flowering. OBJECTIVES: To identify
      variations in the metabolome profiles of pooled and individual samples of leaves
      from female and male plants of M. flexuosa in reproductive phase, and the plant
      in its vegetative phase, using two extraction systems. MATERIAL AND METHODS:
      Extractions of leaves were separately conducted using deuterated water and
      methanol. The extracts were evaluated by NMR spectroscopy and chemometric
      methods. RESULTS: Different NMR spectroscopic profiles were observed for females,
      males, and plants in the vegetative phase. Significant variations were found in
      the carbohydrate and fatty acid contents for the aqueous and methanolic extracts,
      respectively. Although principal component analysis (PCA) has not been efficient
      to distinguish the genders, orthogonal signal correction/partial least squares
      discriminant analysis (OPLS-DA) was able to successfully differentiate male and
      female plants in the reproductive phase, independently on the sampling approach.
      For plants in the vegetative phase, OPLS-DA method from aqueous extracts of M.
      flexuosa leaves also distinguished female samples from the others and showed a
      small overlap between male and young plants, while the classification model was
      not able to be used for prediction. CONCLUSIONS: NMR spectroscopy and chemometric
      based approach was demonstrated to be useful in the metabolic study of dioecy in
      M. flexuosa. The extracts of the leaves allowed for differentiation between male
      and female plants; however, for plants in the vegetative phase, the
      identification of the gender was not effective. Copyright (c) 2018 John Wiley &
      Sons, Ltd.

PMID- 29356157
TI  - In Situ Real-Time Study of the Dynamic Formation and Conversion Processes of
      Metal Halide Perovskite Films.
AB  - Metal halide perovskite solar cells (PSCs) have advanced to the forefront of
      solution-processed photovoltaic techniques and made stunning progress in power
      conversion efficiency (PCE). Further improvements in device performances rely on
      perfecting the structure and morphology of perovskite films. However, undesirable
      defects such as pinholes and grain boundaries are often created in film
      preparations due to lack of knowledge of the precise reaction mechanism. Here, in
      situ grazing-incidence X-ray diffraction (GI-XRD) investigations are performed,
      facilitated by other techniques, on the formation of the widely adopted MAPbI3
      (MA = methylammonium) perovskite films from their intermediate adduct (IA)
      phases. The influences of solvent vapor atmospheres on MAPbI3 films are also
      systematically investigated, where the dynamic conversion processes between
      different phases are visualized in real time. Further in situ GI-XRD and infrared
      spectroscopy measurements reveal that the IA phases contain both N,N
      dimethylformamide and dimethyl sulfoxide (DMSO) as coordinating molecules. By
      tuning the DMSO concentration in perovskite precursors, the ideal perovskite film
      is formed and the best PCE is achieved for the planar MAPbI3 -based PSCs. These
      findings highlight the role of IA phases and the effect of solvent atmospheres on
      the quality of perovskite films, providing direct insights into their growth
      mechanism.

PMID- 29356159
TI  - Secondary Metabolites from Escovopsis weberi and Their Role in Attacking the
      Garden Fungus of Leaf-Cutting Ants.
AB  - The specialized, fungal pathogen Escovopsis weberi threatens the mutualistic
      symbiosis between leaf-cutting ants and their garden fungus (Leucoagaricus
      gongylophorus). Because E. weberi can overwhelm L. gongylophorus without direct
      contact, it was suspected to secrete toxins. Using NMR and mass spectrometry, we
      identified several secondary metabolites produced by E. weberi. E. weberi
      produces five shearinine-type indole triterpenoids including two novel
      derivatives, shearinine L and shearinine M, as well as the polyketides, emodin
      and cycloarthropsone. Cycloarthropsone and emodin strongly inhibited the growth
      of the garden fungus L. gongylophorous at 0.8 and 0.7 MUmol, respectively. Emodin
      was also active against Streptomyces microbial symbionts (0.3 MUmol) of leaf
      cutting ants. Shearinine L instead did not affect the growth of L. gongylophorus
      in agar diffusion assays. However, in dual choice behavioral assays Acromyrmex
      octospinosus ants clearly avoided substrate treated with shearinine L for the
      garden fungus after a 2 d learning period, indicating that the ants quickly learn
      to avoid shearinine L.

PMID- 29356158
TI  - Carbon-Nanotube-Based Thermoelectric Materials and Devices.
AB  - Conversion of waste heat to voltage has the potential to significantly reduce the
      carbon footprint of a number of critical energy sectors, such as the
      transportation and electricity-generation sectors, and manufacturing processes.
      Thermal energy is also an abundant low-flux source that can be harnessed to power
      portable/wearable electronic devices and critical components in remote off-grid
      locations. As such, a number of different inorganic and organic materials are
      being explored for their potential in thermoelectric-energy-harvesting devices.
      Carbon-based thermoelectric materials are particularly attractive due to their
      use of nontoxic, abundant source-materials, their amenability to high-throughput
      solution-phase fabrication routes, and the high specific energy (i.e., W g-1 )
      enabled by their low mass. Single-walled carbon nanotubes (SWCNTs) represent a
      unique 1D carbon allotrope with structural, electrical, and thermal properties
      that enable efficient thermoelectric-energy conversion. Here, the progress made
      toward understanding the fundamental thermoelectric properties of SWCNTs,
      nanotube-based composites, and thermoelectric devices prepared from these
      materials is reviewed in detail. This progress illuminates the tremendous
      potential that carbon-nanotube-based materials and composites have for producing
      high-performance next-generation devices for thermoelectric-energy harvesting.

PMID- 29356160
TI  - Response to Letter: 'Sorrow and cardiovascular events'.

PMID- 29356161
TI  - Neural bases of rhythmic entrainment in humans: critical transformation between
      cortical and lower-level representations of auditory rhythm.
AB  - The spontaneous ability to entrain to meter periodicities is central to music
      perception and production across cultures. There is increasing evidence that this
      ability involves selective neural responses to meter-related frequencies. This
      phenomenon has been observed in the human auditory cortex, yet it could be the
      product of evolutionarily older lower-level properties of brainstem auditory
      neurons, as suggested by recent recordings from rodent midbrain. We addressed
      this question by taking advantage of a new method to simultaneously record human
      EEG activity originating from cortical and lower-level sources, in the form of
      slow (< 20 Hz) and fast (> 150 Hz) responses to auditory rhythms. Cortical
      responses showed increased amplitudes at meter-related frequencies compared to
      meter-unrelated frequencies, regardless of the prominence of the meter-related
      frequencies in the modulation spectrum of the rhythmic inputs. In contrast,
      frequency-following responses showed increased amplitudes at meter-related
      frequencies only in rhythms with prominent meter-related frequencies in the input
      but not for a more complex rhythm requiring more endogenous generation of the
      meter. This interaction with rhythm complexity suggests that the selective
      enhancement of meter-related frequencies does not fully rely on subcortical
      auditory properties, but is critically shaped at the cortical level, possibly
      through functional connections between the auditory cortex and other, movement
      related, brain structures. This process of temporal selection would thus enable
      endogenous and motor entrainment to emerge with substantial flexibility and
      invariance with respect to the rhythmic input in humans in contrast with non
      human animals.

PMID- 29356162
TI  - Comparison of three gamma oscillations in the mouse entorhinal-hippocampal
      system.
AB  - The entorhinal-hippocampal system is an important circuit in the brain, essential
      for certain cognitive tasks such as memory and navigation. Different gamma
      oscillations occur in this circuit, with the medial entorhinal cortex (mEC), CA3
      and CA1 all generating gamma oscillations with different properties. These three
      gamma oscillations converge within CA1, where much work has gone into trying to
      isolate them from each other. Here, we compared the gamma generators in the mEC,
      CA3 and CA1 using optogenetically induced theta-gamma oscillations. Expressing
      channelrhodopsin-2 in principal neurons in each of the three regions allowed for
      the induction of gamma oscillations via sinusoidal blue light stimulation at
      theta frequency. Recording the oscillations in CA1 in vivo, we found that CA3
      stimulation induced slower gamma oscillations than CA1 stimulation, matching in
      vivo reports of spontaneous CA3 and CA1 gamma oscillations. In brain slices ex
      vivo, optogenetic stimulation of CA3 induced slower gamma oscillations than
      stimulation of either mEC or CA1, whose gamma oscillations were of similar
      frequency. All three gamma oscillations had a current sink-source pair between
      the perisomatic and dendritic layers of the same region. Taking advantage of this
      model to analyse gamma frequency mechanisms in slice, we showed using
      pharmacology that all three gamma oscillations were dependent on the same types
      of synaptic receptor, being abolished by blockade of either type A gamma
      aminobutyric acid receptors or alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid/kainate receptors, and insensitive to blockade of N
      methyl-d-aspartate receptors. These results indicate that a fast excitatory
      inhibitory feedback loop underlies the generation of gamma oscillations in all
      three regions.

PMID- 29356163
TI  - Alterations in spontaneous delta and gamma activity might provide clues to detect
      changes induced by amyloid-beta administration.
AB  - Alzheimer's disease (AD) is the most prevalent form of dementia and has an
      increasing incidence. The neuropathogenesis of AD is suggested to be a result of
      the accumulation of amyloid-beta (Abeta) peptides in the brain. To date, Abeta
      induced cognitive and neurophysiologic impairments have not been illuminated
      sufficiently. Therefore, we aimed to examine how spontaneous brain activities of
      rats changed by injection of increasing Abeta doses into the brain hemispheres,
      and whether these changes could be used as a new biomarker for the early
      diagnosis of the AD. Rats were randomized into following groups: sham (Sham) and
      seven Abeta-treated (i.c.v.) groups in increasing concentrations (from Abeta-1 to
      Abeta-7). After recovery, EEG recordings were obtained from implanted electrodes
      from eight electrode locations, and then, spectral and statistical analyses were
      performed. A significant decrement in gamma activity was observed in all Abeta
      groups compared with the sham group. In delta activity, we observed significant
      changes from Abeta-4 to Abeta-7 group compared with sham group. Delta coherence
      values were decreased from Abeta-4 to Abeta-7 and Abeta-5 to Abeta-7 groups for
      frontal and temporal electrode pairs, respectively. A gradual increment was
      observed in Abeta1-42 level till Abeta-4 group. Positive correlation for global
      delta power and negative correlation for global gamma power between Abeta1-42
      peptide levels were detected. Consequently, it is conceivable to suggest gamma
      oscillation might be used to detect early stages of AD. Moreover, changes in
      delta activity provide information about the onset of major pathologic changes in
      the progress of AD.

PMID- 29356164
TI  - Tracking actinic keratosis of face and scalp treated with 0.015% ingenol mebutate
      to identify clinical and dermoscopic predictors of treatment response.
AB  - BACKGROUND: Ingenol mebutate (IngMeb) 0.015% gel is an approved field treatment
      option for non-hyperkeratotic non-hypertrophic actinic keratosis (AK) of face and
      scalp. Efficacy of IngMeb has been assessed only on a clinical ground, in the
      majority of studies. Dermoscopy is a pivotal tool for the diagnosis of AK, while
      its role in evaluating the response to non-surgical therapies for AK has not been
      fully defined. OBJECTIVES: Our study aims to determine whether some dermoscopic
      features of AK of the face and scalp areas may independently predict the response
      to IngMeb therapy. METHODS: Clinical and dermoscopic responses, 1 month after
      0.015% IngMeb therapy, were retrospectively evaluated using a per-patient and per
      lesion approach. Safety was evaluated through local skin reaction composite score
      calculation. Demographic, clinical and dermoscopic factors were then evaluated
      via univariate and multivariate logistic regression analysis to assess
      independent predictors of response. RESULTS: Fifty-five patients with 245 AKs
      were enrolled. Clinically, per-patient response evaluation identified 25 (45.4%)
      poor/partial and 30 (54.5%) complete responders, corresponding on a per-lesion
      approach to 66 (26.9%) and 179 (73.1%) AKs, respectively. Dermoscopy reclassified
      14 patients in the per-patient and 48 AKs in the per-lesion analysis from
      complete to poor/partial responders. Multivariate logistic regression analysis
      showed that AKs dermoscopically characterized by red pseudonetwork and located on
      the face were independently associated with a complete dermoscopic response to
      0.015% IngMeb therapy, while microerosions were negative predictors. CONCLUSION:
      Specific dermoscopic features of AK may predict the response to 0.015% IngMeb
      therapy, together with the location on the face.

PMID- 29356165
TI  - Period prevalence and reporting rate of medication errors among nurses in Iran: A
      systematic review and meta-analysis.
AB  - AIMS: To estimate the 1-year period prevalence of medication errors and the
      reporting rate to nurse managers among nurses working in hospitals in Iran.
      BACKGROUND: Medication errors are one of the main factors affecting the quality
      of hospital services and reducing patient safety in health care systems. METHOD:
      A literature search from Iranian and international scientific databases was
      developed to find relevant studies. Meta-regression was used to identify which
      characteristics may have a confounding effect on the pooled prevalence estimates.
      RESULTS: Based on the final 22 studies with 3556 samples, the overall estimated 1
      year period prevalence of medication errors and its reporting rate to nurse
      managers among nurses were 53% (95% confidence interval, 41%-60%) and 36% (95%
      confidence interval, 23%-50%), respectively. The meta-regression analyses
      indicated that the sex (female/male) ratio was a statistically significant
      predictor of the prevalence of medication errors (p < .05), but not of the
      prevalence of reporting medication errors to nurse managers. CONCLUSION: The
      period prevalence of medication errors among nurses working in hospitals was high
      in Iran, whereas its reporting rate to nurse managers was low. IMPLICATIONS FOR
      NURSING MANAGEMENT: Continuous training programmes are required to reduce and
      prevent medication errors among nursing staff and to improve the reporting rate
      to nurse managers in in Iran.

PMID- 29356166
TI  - Different responses of the right superior temporal sulcus to visual movement
      feedback during self-generated vs. externally generated hand movements.
AB  - An important implication of several recent accounts of motor control is that
      sensory feedback from self-generated movements is relatively attenuated based on
      predictions issued by the agent's motor system. Such a relative attenuation of
      sensory information during actions has already been demonstrated in the
      somatosensory domain. Here, we used functional magnetic resonance imaging (fMRI)
      and a virtual reality-based setup to investigate a potential attenuation of brain
      responses to realistic visual movement feedback during active vs. passive right
      hand movements. The participants' right unseen hand was rotated either by the
      participants themselves or by the experimenter, while the participants received
      visual movement feedback via a photorealistic virtual 3D hand driven by their
      real hand movements, or received no visual feedback. We observed a significant
      interaction between movement type (active vs. passive) and movement feedback
      (vision vs. no vision) in the right superior temporal sulcus (STS), which showed
      relatively attenuated blood-oxygen-level-dependent (BOLD) signal differences in
      movements with vs. without visual feedback when those movements were actively vs.
      passively executed. This finding suggests that STS activity caused by visual
      feedback from the moving body may be attenuated based on the agent's motor
      predictions.

PMID- 29356168
TI  - Altered transcription of glutamatergic and glycinergic receptors in spinal cord
      dorsal horn following spinal cord transection is minimally affected by passive
      exercise of the hindlimbs.
AB  - Gene expression is altered following a spinal transection (STx) in both motor and
      sensory systems. Exercise has been shown to influence gene expression in both
      systems post-STx. Gene expression alterations have also been shown in the dorsal
      root ganglia and nociceptive laminae of the spinal cord following either an
      incomplete spinal cord injury (SCI) or a contusive SCI. However, the effect of
      STx and exercise on gene expression in spinal cord laminae I-III has not fully
      been examined. Therefore, the purpose of this study was to determine whether gene
      expression in laminae I-III is altered following STx and determine whether
      superimposed passive exercise of the hindlimbs would influence gene expression
      post-STx in laminae I-III. Laser capture microdissection was used to selectively
      harvest laminae I-III of lumbar spinal cord sections, and quantitative RT-PCR was
      used to examine relative expression of 23 selected genes in samples collected
      from control, STx and STx plus exercise rats. We demonstrate that post-STx, gene
      expression for metabotropic glutamate receptors 1, 5 and 8 were up-regulated,
      whereas ionotropic glutamatergic receptor (Glur2) and glycinergic subunit GLRA1
      expression was down-regulated. Daily exercise attenuated the down-regulation of
      Glur2 gene expression in laminae I-III. Our results demonstrate that in a STx
      model, gene expression is altered in laminae I-III and that although passive
      exercise influences gene expression in both the motor and sensory systems, it had
      a minimal effect on gene expression in laminae I-III post-STx.

PMID- 29356167
TI  - Targeting of miR-31/96/182 to the Numb gene during head and neck oncogenesis.
AB  - BACKGROUND: MicroRNAs (miRNAs) play crucial roles in head and neck squamous cell
      carcinoma (HNSCC). This study investigates whether miR-31, miR-96, and miR-182
      are involved in targeting Numb during HNSCC. METHODS: The expression of miR
      31/96/182 in tumor tissues was analyzed. Reporter assay, knockdown, expression,
      and oncogenic analysis were carried out in cell lines. RESULTS: Upregulation of
      miR-31/96/182 was detected in tumor tissues. In addition, advanced tumors showed
      higher expression levels of these miRNAs. The expression of these miRNAs was
      upregulated after treatment with areca ingredients (P < .01 or P < .001). These
      miRNAs directly targeted the 3' untranslated region (UTR) sequence of the Numb
      gene. An increased migration and invasion of HNSCC cells was associated with the
      exogenous expression of miR-31/96/182 (P < .01 or P < .001), and this was
      reverted by expression of Numb. CONCLUSION: This study provides new evidence
      demonstrating that there is frequent and concordant upregulation of miR-31, miR
      96, and miR-182 during HNSCC and these miRNAs co-target Numb.

PMID- 29356169
TI  - Role of dental hardware in oral cavity squamous cell carcinoma in the low-risk
      nonsmoker nondrinker population.
AB  - BACKGROUND: Oral cavity squamous cell carcinoma (SCC) arising in nonsmokers and
      nondrinkers remains poorly characterized. We hypothesized that these patients had
      prior exposure to metallic dental hardware. METHODS: We utilized a questionnaire
      querying the lifetime oral health status of 54 patients. Demographics and
      extensive oral health history were collected. RESULTS: The majority of patients
      (74%) had prior exposure to metallic dental hardware. The younger population with
      almost exclusively oral tongue cancer had a high prevalence of metallic
      orthodontic braces (40%) within 15 years before diagnosis. In the 51+ year age
      group, 82% had crowns, dental implants, and/or dentures with metallic elements.
      CONCLUSION: Exposure to metallic dental hardware has increased in the past few
      decades given the rise of orthodontic braces and older adults retaining more
      teeth. Although this study does not prove a causal relationship between oral
      cavity SCC and dental hardware, this is a step toward identifying and
      investigating their role.

PMID- 29356171
TI  - The impact of closed-loop electronic medication management on time to first dose:
      a comparative study between paper and digital hospital environments.
AB  - : Closed-loop electronic medication management systems (EMMS) are recognised as
      an effective intervention to improve medication safety, yet evidence of their
      effectiveness in hospitals is limited. Few studies have compared medication
      turnaround time for a closed-loop electronic versus paper-based medication
      management environment. OBJECTIVE: To compare medication turnaround times in a
      paper-based hospital environment with a digital hospital equipped with a closed
      loop EMMS, consisting of computerised physician order entry, profiled automated
      dispensing cabinets packaged with unit dose medications and barcode medication
      administration. METHOD: Data were collected during 2 weeks at three private
      hospital sites (one with closed-loop EMMS) within the same organisation network
      in Queensland, Australia. Time between scheduled and actual administration times
      was analysed for first dose of time-critical and non-critical medications located
      on the ward or sourced via pharmacy. KEY FINDINGS: Medication turnaround times at
      the EMMS site were less compared to the paper-based sites (median, IQR: 35 min, 8
      57 min versus 120 min, 30-180 min, P < 0.001). For time-critical medications, 77%
      were administered within 60 min of scheduled time at the EMMS site versus 38% for
      the paper-based sites. Similar difference was observed for non-critical
      medications, 80% were administered within 60 min of their scheduled time at the
      EMMS site versus 41% at the paper-based facilities. CONCLUSION: The study
      indicates medication turnaround times utilising a closed-loop EMMS are less
      compared to paper-based systems. This improvement may be attributable to
      increased accessibility of medications using automated dispensing cabinets and
      electronic medication administration records flagging tasks to nurses in real
      time.

PMID- 29356170
TI  - T-cell papulosis associated with B-cell malignancy: a distinctive
      clinicopathologic entity.
AB  - BACKGROUND: A distinctive eruption referred to as 'insect bite-like reaction' or
      'eosinophilic dermatosis of haematological malignancy' has been described during
      the course of haematological B-cell malignancies (BCM). However, its clinical
      evolution, histopathological features and pathogenesis remain unclear.
      OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and
      relationship with the underlying BCM. METHODS: In this multicenter retrospective
      study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM
      and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo
      vesicles and/or nodules were included. Clinical, histopathological,
      immunohistochemical and molecular data were reviewed. RESULTS: No significant
      insect bite history or seasonal predominance was recorded. Patients had pruritic
      papules (81%), papulo-vesicles (43%) and nodules (38%), often predominated in the
      head and neck region (84%), without complete remission periods in most cases
      (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%).
      Histological and immunohistochemical review showed a dense dermal lymphocytic
      infiltrate predominantly composed of T lymphocytes (100%), with frequent
      eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic)
      pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides;
      clusters of tumour B cells were identified in 47% of cases using appropriate
      phenotyping markers. In 10/14 cases (71.4%) tested for B-cell IgH gene
      rearrangement, a B-cell clone was identified in skin lesions (identical to the
      blood clone in nine cases), whereas no T-cell clone was present. CONCLUSION: We
      propose the denomination 'T-cell papulosis associated with B-cell malignancy'
      (TCP-BCM) for this distinctive eruption. Although resulting in various
      histopathological pictures, it can be easily recognized by clinicians and may be
      identified by informed pathologists relying on some key features. An
      extravasation of tumour B cells with skin-homing properties associated with a
      secondary, predominant, T-cell immune reaction could explain the
      clinicopathologic aspect and the prolonged regressive and recurrent course of the
      disease.

PMID- 29356172
TI  - Therapy response was not altered by HLA-Cw6 status in psoriasis patients treated
      with secukinumab: a retrospective case series.

PMID- 29356173
TI  - 9-Membered Carbocycles: Strategies and Tactics for their Synthesis.
AB  - Many natural products comprising a nine-membered carbocyclic core structure
      exhibit interesting biological effects. However, only a minority have succumbed
      to their synthesis in the past. The synthesis of functionalized nine-membered
      carbocycles still remains a challenging goal for synthetic chemists, mainly due
      to their high ring strain. Different strategies to overcome the unfavorable
      enthalpic and entropic factors associated with their formation are highlighted in
      this Concept article. The presented methods are classified into two different
      categories: (1) the ring-expansion of smaller rings or the ring-contraction of
      larger rings and (2) the direct cyclization of acyclic precursors.

PMID- 29356174
TI  - Adolescents' alcohol use and strength of policy relating to youth access, trading
      hours and driving under the influence: findings from Australia.
AB  - AIMS: To determine (i) whether the strength of Australian alcohol control policy
      in three domains (youth access, trading hours and drink driving) changed during
      the 2000s; and (ii) estimate associations between these policies and adolescent
      drinking after adjusting for television alcohol advertising exposures, alcohol
      outlet density, alcohol price changes, exposure to negative articles about
      alcohol in daily newspapers and adult drinking prevalence. DESIGN: Repeated cross
      sectional surveys conducted triennially from 2002 to 2011. Multi-level modelling
      examined the association between alcohol control policies and drinking prevalence
      after adjusting for covariates. SETTING: Four Australian capital cities between
      2002 and 2011. PARTICIPANTS: Students aged 12-17 years participating in a
      triennial national representative school-based survey (sample size range/survey:
      9805-13 119). MEASUREMENTS: Outcome measures were: past month drinking and risky
      drinking (5+ drinks on a day) in the past 7 days. Policy strength in each of
      three domains (youth access, trading hours, drink-driving) were the key predictor
      variables. Covariates included: past 3-month television alcohol and alcohol
      control advertising, alcohol outlet density, alcohol price change, negatively
      framed newspaper alcohol articles, adult drinking prevalence and student
      demographic characteristics. FINDINGS: During the study period, the strength of
      youth access policies increased by 10%, trading hours policies by 14% and drink
      driving policies by 58%. Past-month and risky drinking prevalence decreased (e.g.
      past-month: 2002: 47.4% to 2011: 26.3%). Multivariable analyses that included all
      policy variables and adjusted for year, student and other covariates showed past
      month drinking to be associated inversely with stronger trading hours policies
      [odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.69, 0.94], but not
      youth access (OR = 0.92 95% CI = 0.81, 1.04) or drink-driving (OR = 1.00, 95% CI
      = 0.93, 1.09). Risky drinking was associated inversely with stronger youth access
      policies (OR = 0.82, 95% CI = 0.69, 0.98), but not trading hours (OR = 0.85, 95%
      CI = 0.66, 1.09) or drink-driving (OR = 1.02, 95% CI = 0.90, 1.14) policies.
      CONCLUSIONS: Population-directed policies designed to reduce alcohol availability
      and promotion may reduce adolescents' alcohol use.

PMID- 29356175
TI  - Radioprotective effects of dammarane sapogenins against 60 Co-induced
      myelosuppression in mice.
AB  - Radiotherapy frequently induces failure of hematopoietic system and leads to
      myelosuppression. The objective of this study was to investigate the protective
      effect of dammarane sapogenins (DS), the hydrolysed product of the constituent
      ginsenosides of Panax ginseng, which are produced by gut metabolism, on radiation
      induced hematopoietic injury. Mice were exposed to 3.5 Gy 60 Co gamma-rays of
      total body radiation at a dose rate of 1.60 Gy per minute and treated with DS or
      granulocyte colony-stimulating factor immediately after radiation. The general
      condition of the mice, the peripheral blood cell counts, multiple colony forming
      unit (CFU) assays of hematopoietic progenitor cells, hematopoietic stem cell
      counts, bone marrow histology, and spleen colony forming unit counts were then
      investigated. Our results indicated that administration with DS could ameliorate
      60 Co-irradiation induced damage and significantly increase the number of
      peripheral blood cells (white blood cells and platelets), 5 types of
      hematopoietic progenitor cells CFU (CFU-GM, CFU-E, BFU-E, CFU-Meg, and CFU-GEMM),
      hematopoietic stem cell (Lin- c-kit+ Scal-1+ ) numbers, and CFUs in the spleen,
      as well as improved bone marrow histopathology. All together, these results
      confirmed the enhancement of DS on hematopoiesis.

PMID- 29356176
TI  - Tools of the trade: Improving nurses' ability to access and evaluate research.
AB  - AIM: To evaluate the effect of a manager-required RN competency on staff nurses'
      perceived knowledge, ability and frequency of information-seeking activities.
      BACKGROUND: Basing clinical practice on research and standards of care is
      essential to delivering appropriate care with optimal outcomes. Nurses'
      information-seeking abilities are critical for acquiring evidence-based answers
      to aid clinical decision-making, yet nurses under-utilize library resources and
      report barriers. A unit manager sought to test the effect of an innovative
      competency for acquiring and appraising evidence for practice. METHODS: This
      longitudinal descriptive study evaluated 28 nurses before and after a 1-hr class,
      as well as 5 months later. The class covered library information services and the
      basics of critiquing research articles. RESULTS: Nurses had statistically
      significant improvements in four of five items measuring knowledge/ability and
      four of five items measuring frequency of information-seeking activities. At 5
      months, most knowledge/ability items increased. There was no effect of nurse
      characteristics on outcomes. CONCLUSIONS: A required competency improved nurses'
      knowledge, ability and frequency of acquiring and appraising evidence with a
      single 1-hr class and a hands-on practice activity. Unit managers can have great
      impact on nurses' use of evidence for practice.

PMID- 29356177
TI  - Proline-rich transmembrane protein 2-negative paroxysmal kinesigenic dyskinesia:
      Clinical and genetic analyses of 163 patients.
AB  - BACKGROUND: Paroxysmal kinesigenic dyskinesia is the most common type of
      paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic
      dyskinesia worldwide are attributable to proline-rich transmembrane protein 2
      mutations. OBJECTIVE: The objective of this study was to investigate potential
      causative genes and clinical characteristics in proline-rich transmembrane
      protein 2-negative patients with paroxysmal kinesigenic dyskinesia. METHODS: We
      analyzed clinical manifestations and performed exome sequencing in a cohort of
      163 proline-rich transmembrane protein 2-negative probands, followed by filtering
      data with a paroxysmal movement disorders gene panel. Sanger sequencing,
      segregation analysis, and phenotypic reevaluation were used to substantiate the
      findings. RESULTS: The clinical characteristics of the enrolled 163 probands were
      summarized. A total of 39 heterozygous variants were identified, of which 33 were
      classified as benign, likely benign, and uncertain significance. The remaining 6
      variants (3 novel, 3 documented) were pathogenic and likely pathogenic. Of these,
      3 were de novo (potassium calcium-activated channel subfamily M alpha 1,
      c.1534A>G; solute carrier family 2 member 1, c.418G>A; sodium voltage-gated
      channel alpha subunit 8, c.3640G>A) in 3 sporadic individuals, respectively. The
      other 3 (paroxysmal nonkinesiogenic dyskinesia protein, c.956dupA; potassium
      voltage-gated channel subfamily A member 1, c.765C>A; Dishevelled, Egl-10, and
      Pleckstrin domain containing 5, c.3311C>T) cosegregated in 3 families. All 6
      cases presented with typical paroxysmal kinesigenic dyskinesia characteristics,
      except for the Dishevelled, Egl-10, and Pleckstrin domain containing 5 family,
      where the proband's mother had abnormal discharges in her temporal lobes in
      addition to paroxysmal kinesigenic dyskinesia episodes. CONCLUSIONS: Our findings
      extend the genotypic spectrum of paroxysmal kinesigenic dyskinesia and establish
      the associations between paroxysmal kinesigenic dyskinesia and genes classically
      related to other paroxysmal movement disorders. De novo variants might be a cause
      of sporadic paroxysmal kinesigenic dyskinesia. (c) 2018 International Parkinson
      and Movement Disorder Society.

PMID- 29356178
TI  - Programmed death ligand-1 expression as immunotherapeutic target in sinonasal
      cancer.
AB  - BACKGROUND: Sinonasal cancer carries a poor prognosis, especially in recurrent
      stages, and it is a disease with very limited treatment options. METHODS: The
      expression of programmed death ligand-1 (PD-L1) as a marker for immunotherapy was
      evaluated in 53 sinonasal squamous cell carcinoma (SCC) and 126 intestinal-type
      adenocarcinoma (ITAC) samples. Results were correlated to clinicopathological
      characteristics and follow-up data. RESULTS: Membranous PD-L1 staining of tumor
      cells was observed in 34% (18/53) of the sinonasal SCC samples and in 17%
      (22/126) of the ITAC samples. The PD-L1 positivity on infiltrating immune cells
      occurred in 45% (24/53) of the sinonasal SCC samples and in 33% (41/126) of the
      ITAC samples. Expression of PD-L1 showed no correlation to clinicopathological
      parameters and was not an independent risk factor for survival. CONCLUSION: The
      PD-L1 positivity does not seem to have prognostic value. However, a proportion of
      patients with sinonasal SCC and ITAC may benefit from therapy with immune
      checkpoint inhibitors that recently have been approved for clinical application
      in head and neck cancer.

PMID- 29356179
TI  - Neutrophil-to-lymphocyte ratio in head and neck cancer prognosis: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Hematologic markers, such as the neutrophil-to-lymphocyte ratio
      (NLR), characterize the inflammatory response to cancer and are associated with
      poorer survival in various malignancies. We evaluate the effect of pretreatment
      NLR on overall survival (OS) in patients with head and neck squamous cell
      carcinoma (HNSCC). METHODS: Using multiple databases, a systematic search for
      articles evaluating the effect of NLR on OS in patients with HNSCC was performed.
      An inverse variation, random-effects model was used to analyze the data. RESULTS:
      A total of 24 of 241 articles, including 6479 patients, were analyzed. The
      combined hazard ratio for OS in patients with an elevated NLR (range 2.04-5) was
      1.78 (confidence interval [CI] 1.53-2.07; P < .0001). The hazard ratios for site
      specific cancer: oral cavity 1.56 CI 1.23-1.98 (P < .001), nasopharynx 1.66 CI
      1.35-2.04 (P < .001), larynx 1.55 CI 1.26-1.92 (P < .001), and hypopharynx 2.36
      CI 1.54-3.61 (P < .001). CONCLUSION: An elevated NLR is predictive of poorer OS
      in patients with HNSCC.

PMID- 29356180
TI  - Severe adverse cutaneous drug reactions to antiepileptic drugs: 18 years of
      experience in a tertiary referral dermatology clinic in Turkey.

PMID- 29356181
TI  - Guideline-compliant prescription of biologicals and possible barriers in
      dermatological practices in Bavaria.
AB  - INTRODUCTION: Psoriasis and urticaria are chronic inflammatory skin diseases,
      which account for a substantial socioeconomic burden and severely affect
      patients' quality of life. According to the respective German guidelines,
      biologicals can be used for the treatment of severe forms of these diseases.
      However, only a minority of patients receive this advised treatment. OBJECTIVE:
      To analyse the prescription of biologicals according to the German national
      guidelines for psoriasis and chronic spontaneous urticaria and to assess possible
      barriers to prescription. MATERIALS AND METHODS: Cross-sectional, questionnaire
      based study including all Bavarian dermatologists based in private practices.
      Linear and logistic regression models were used to identify significant
      influencing factors on the perception of possible barriers. RESULTS: Between
      January 2017 and February 2017, a total of 137 (of 499) dermatologists
      participated. Of all patients with moderate to severe psoriasis and chronic
      spontaneous urticaria, participating dermatologists indicated treating 14.2% and
      6.9% with biologicals, respectively. The most prevalent barriers to prescription
      were the high cost of the therapy, the low reimbursement and the fear of
      recourse. Analysis showed that age, years spent working in a dermatological
      hospital and the number of patients treated with moderate to severe psoriasis
      affect the perception of many barriers. Furthermore, age and barriers related to
      physician factors and external factors were identified as modifiers to the
      prescription scheme of dermatologists. CONCLUSIONS: The role of clinical
      education and the importance of external and economic barriers in comparison with
      medical barriers have to be emphasised. Guideline-compliant use of biologicals
      has to be optimised. Further research is needed to ascertain not only a barrier
      pattern for Bavaria but also for wider settings. Actions based on this for
      psoriasis are needed to achieve the goal of the WHO Global Psoriasis Report to
      strengthen the role of patient-centred care and improve the quality of life of
      affected patients. Analogue, this applies also for urticaria.

PMID- 29356182
TI  - Retinoic acid signalling is a candidate regulator of the expression of pituitary
      specific transcription factor Prop1 in the developing rodent pituitary.
AB  - Development of the anterior pituitary proceeds via spatiotemporal patterning of
      transcription factors and signalling molecules. Among them, retinoic acid (RA)
      functions as an important signalling molecule for vertebrate organogenesis in
      many tissues. However, little is known regarding the target genes in the
      developing pituitary. The present study aimed to clarify the relationship between
      endogenous RA signalling and mRNA expression of the pituitary-specific
      transcription factor Prop1 in the pituitary primordium of Rathke's pouch. Gene
      expression analysis and in situ hybridisation demonstrated that retinaldehyde
      dehydrogenases (Raldhs) and all types of RA receptors (Rars) are expressed at the
      level of transcription in the rat Rathke's pouch. Ex vivo organ culture using
      Rathke's pouch and an in vitro reporter assay demonstrated that RA signalling
      increases the expression level of Prop1 via RARalpha. Moreover, a reporter assay
      using serial truncated constructs of the 5'-upstream region of mouse Prop1
      revealed a predicted cis-regulatory element of RARalpha. This is the first report
      of a relationship between RA signalling and Prop1-expression during early
      pituitary development.

PMID- 29356183
TI  - Whole brain white matter histogram analysis of diffusion tensor imaging data
      detects microstructural damage in mild cognitive impairment and alzheimer's
      disease patients.
AB  - BACKGROUND: Amnestic mild cognitive impairment (MCI) is a transitional stage
      between normal aging and Alzheimer's disease (AD). However, the clinical
      conversion from MCI to AD is unpredictable. Hence, identification of noninvasive
      biomarkers able to detect early changes induced by dementia is a pressing need.
      PURPOSE: To explore the added value of histogram analysis applied to measures
      derived from diffusion tensor imaging (DTI) for detecting brain tissue
      differences between AD, MCI, and healthy subjects (HS). STUDY TYPE: Prospective.
      POPULATION/SUBJECTS: A local cohort (57 AD, 28 MCI, 23 HS), and an Alzheimer's
      Disease Neuroimaging Initiative (ADNI) cohort (41 AD, 58 MCI, 41 HS). FIELD
      STRENGTH: 3T. Dual-echo turbo spin echo (TSE); fluid-attenuated inversion
      recovery (FLAIR); modified-driven-equilibrium-Fourier-transform (MDEFT);
      inversion-recovery spoiled gradient recalled (IR-SPGR); diffusion tensor imaging
      (DTI). ASSESSMENT: Normal-appearing white matter (NAWM) masks were obtained using
      the T1 -weighted volumes for tissue segmentation and T2 -weighted images for
      removal of hyperintensities/lesions. From DTI images, fractional anisotropy (FA),
      mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) were
      obtained. NAWM histograms of FA, MD, AXD, and RD were derived and characterized
      estimating: peak height, peak location, mean value (MV), and quartiles (C25, C50,
      C75), which were compared between groups. Receiver operating characteristic (ROC)
      and area under ROC curves (AUC) were calculated. To confirm our results, the same
      analysis was repeated on the ADNI dataset. STATISTICAL TESTS: One-way analysis of
      variance (ANOVA), post-hoc Student's t-test, multiclass ROC analysis. RESULTS:
      For the local cohort, C25 of AXD had the maximum capability of group
      discrimination with AUC of 0.80 for "HS vs. patients" comparison and 0.74 for "AD
      vs. others" comparison. For the ADNI cohort, MV of AXD revealed the maximum group
      discrimination capability with AUC of 0.75 for "HS vs. patients" comparison and
      0.75 for "AD vs. others" comparison. DATA CONCLUSION: AXD of NAWM might be an
      early marker of microstructural brain tissue changes occurring during the AD
      course and might be useful for assessing disease progression. LEVEL OF EVIDENCE:
      1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.

PMID- 29356184
TI  - Estimation of the radiation dose for pediatric CBCT indications: a prospective
      study on ProMax3D.
AB  - BACKGROUND: An increasing number of CBCT units and a wide variability of
      radiation doses have been reported in dentistry lately. AIM: To estimate the
      effective, cumulative, and organ absorbed doses in children exposed to CBCT over
      2 years. DESIGN: A prospective study was conducted in children who underwent CBCT
      diagnostic imaging with the ProMax3D machine. Organ and effective doses were
      calculated by Monte Carlo simulation using 5- and 8-year-old pediatric voxel
      phantoms. Extrapolation procedures were applied to estimate doses for other ages
      and CBCT protocols used in clinical conditions. RESULTS: The median effective
      dose was 137.9 MUSv, and the median cumulative dose was 231.4 MUSv. Statistically
      significant differences in the effective doses and cumulative doses were found
      for various indications of CBCT in children (P < 0.001). The median absorbed
      organ dose for brain and thyroid was significantly higher for the clinical
      condition that required large FOVs (2.5 mGy and 1.05 mGy, respectively) compared
      to medium (0.19 and 0.51 mGy) and small FOVs (0.07 and 0.24 mGy; P < 0.05). The
      radiation dose of salivary glands did not vary significantly with FOV.
      CONCLUSION: The results revealed the variation of CBCT doses and the influence of
      FOV size in pediatric exposure.

PMID- 29356185
TI  - Medicinal uses, pharmacology, and phytochemistry of Convolvulaceae plants with
      central nervous system efficacies: A systematic review.
AB  - Central nervous system (CNS) disorders play a major impact on individual lives
      and place a severe strain on health care resources. Convolvulaceae is a family
      comprising approximately 1,600-1,700 species grouped in 55-60 genera, and many
      species are reported to have an effect on CNS functions. A systematic review of
      the literature studies was carried out to summarize available evidences on
      Convolvulaceae plants with CNS efficacies. This review is based on various data
      sources such as Google Scholar, Web of Science, Scopus, PubMed, and Wanfang Data.
      A total of 200 related articles were included in this review. According to the
      research result, 54 Convolvulaceae species are suggested to display CNS
      efficacies historically, and 46 species have been evaluated for their CNS
      efficacies. In addition, 67 compounds from 16 Convolvulaceae species are
      recognized to possess CNS efficacies. Despite great progress made through
      pharmacology and phytochemistry studies on CNS active Convolvulaceae species,
      more exploratory research is needed to gain a better understanding of the CNS
      efficacies of this plant family.

PMID- 29356186
TI  - The Blomia tropicalis allergen Blo t 7 stimulates innate immune signalling
      pathways through TLR2.
AB  - BACKGROUND: Although the house dust mite species Blomia tropicalis is a leading
      cause of allergic diseases in tropical and subtropical regions, the
      identification and characterization of the allergenic proteins remain incomplete.
      OBJECTIVE: We aimed to characterize a recombinant form of Blo t 7 (rBlo t 7) in
      terms of IgE reactivity, lipid-binding activity and ability to stimulate innate
      immunity. METHODS: The mature Blo t 7 cDNA was cloned by PCR methods for the
      expression of a secreted form of the allergen in P. pastoris. The IgE reactivity
      to purified rBlo t 7 as well as the potential cross-reactivity with Der p 7 was
      determined by ELISA. The lipid-binding capacity of rBlo t 7 was assayed using
      fluorescent lipid probes. The stimulation of TLR2 signalling pathway by rBlo t 7
      was examined in cell activation and reporter assays. RESULTS: The amplified
      mature Blo t 7 cDNA revealed the presence of a 60 base pair insertion compared
      with the reference sequence registered in the GenBank database. Multiple protein
      sequence alignments of group 7 mite allergens confirmed that this longer deduced
      amino acid sequence was the authentic Blo t 7 polypeptide chain. Analysis of IgE
      reactivity can classify rBlo t 7 as an intermediate B. tropicalis allergen which
      displayed weak cross-reactivity with Der p 7. Purified rBlo t 7 was shown to bind
      selectively the naturally fluorescent lipid probe cis-parinaric (cPNA) with a
      dissociation constant of 2 MUmol/L. The group 7 Blomia allergen stimulated the
      TLR2-, NF-kB- and MAPK-dependent production of IL-8 and GM-CSF in respiratory
      epithelial cells. CONCLUSIONS & CLINICAL RELEVANCE: Through its propensity to
      transport fatty acids/lipids and to stimulate TLR2 signalling pathways in airway
      epithelial cells, Blo t 7 can represent a key allergen for the initiation of the
      B. tropicalis-induced airway inflammation.

PMID- 29356187
TI  - Evaluation of margins in head and neck squamous cell carcinoma from the surgeon's
      perspective.
AB  - BACKGROUND: The surgeon's evaluation of resection status based on frozen section
      analysis during operation and pathological examination of resected specimens
      often differ. For this study, we recapitulated the surgeon's perspective during
      an operation, accordingly classified the evaluation of margins by the surgeon,
      and analyzed its impact on the outcome compared with the pathological results.
      METHODS: This was a retrospective analysis. As data sources, paper-based and
      digital patient files, as well as the Munich Cancer Registry database were used.
      RESULTS: Three hundred ninety-six cases were included in this analysis. Only the
      evaluation of margins by the surgeon influenced local control, and the
      pathological results influenced disease-free survival (DFS). Surprisingly,
      margins of >5 mm of normal tissue to cancer growth led to local control and
      overall survival (OS) significantly worse than 1 to 5-mm resections. CONCLUSION:
      The evaluation of margins by the surgeon is of significant importance for local
      control and OS. It is largely based on frozen section analysis, which, therefore,
      should be used whenever possible.

PMID- 29356188
TI  - One-Carbon Oxidative Annulations of 1,3-Enynes by Catalytic C-H Functionalization
      and 1,4-Rhodium(III) Migration.
AB  - Rhodium(III)-catalyzed C-H functionalization-oxidative annulations of aromatic
      substrates with 1,3-enynes that contain allylic hydrogen atoms cis to the alkyne
      are described. The key step in these reactions is an alkenyl-to-allyl 1,4
      rhodium(III) migration to give electrophilic pi-allylrhodium(III) species.
      Nucleophilic trapping of these species gives heterocycles such as benzopyrans,
      isobenzofuranones, and isoindolinones.

PMID- 29356189
TI  - Effect of time to simulation and treatment for patients with oropharyngeal cancer
      receiving definitive radiotherapy in the era of risk stratification using smoking
      and human papillomavirus status.
AB  - BACKGROUND: The effect of increasing time to definitive radiotherapy (RT) for
      patients with oropharyngeal squamous cell carcinoma (SCC) is unknown. METHODS:
      Nodal tumor volumes at staging and simulation were compared for patients with
      oropharyngeal SCC. Time from staging to initiation of RT was tabulated. The
      primary endpoint of interest was nodal progression at simulation. RESULTS:
      Increasing time to simulation was associated with nodal progression in 144
      patients (r = 0.474; P < .001). Patients with human papillomavirus (HPV)
      associated oropharyngeal SCC were more likely to have nodal progression (50% vs
      26%; P = .008). A threshold of 32 days was associated (sensitivity 77.9% and
      specificity 60.2%) with nodal progression (P < .001). Increasing time from
      staging to treatment initiation was associated with a greater risk of distant
      failure (hazard ratio [HR] 4.157; 95% confidence interval [CI] 1.170-14.764) but
      not progression-free survival (PFS; P = .179) or overall survival (OS; P = .474).
      CONCLUSION: Increasing time before RT for patients with oropharyngeal SCC is
      associated with nodal progression and increased hazard of distant failure,
      although not PFS or OS in our population.

PMID- 29356190
TI  - Decreased superficial surgical site infections, shortened hospital stay, and
      improved quality of life due to incisional negative pressure wound therapy after
      reversal of double loop ileostomy.
AB  - This single-center prospective, controlled observational study investigates the
      impact of incisional negative pressure wound therapy on wound healing processes
      and its potency to prevent superficial surgical site infections (SSSI) after
      reversal of a double loop ileostomy. Furthermore, this study gains insight in
      socioeconomic aspects, like duration of hospital stay and, for the first time,
      patient's quality of life during the incisional negative pressure wound
      treatment. To address this question, an interventional group of 24 patients
      treated with incisional negative pressure wound therapy (Prevena incisional wound
      management system, KCI, Germany) and a respective control cohort of 25 patients
      treated with a standard sterile dressing were observed for 30 days in the
      postoperative course. Postoperative incisional negative pressure wound therapy
      resulted in statistically significant decreasing duration of hospital stay (6
      days vs. 9 days, p = 0.019) and lower rates of SSSIs (12.5% vs. 20.0%, p = 0.478)
      in accordance with a not statistically significant decreased necessity of
      postoperative antibiotic therapy (12.5% vs. 36%, p = 0.051). To survey subjective
      items of well-being and quality of life, all patients were asked to answer a
      questionnaire. Patients of both groups noticed increasing quality of life after
      reversal of their ileostomy. However, patients treated with an incisional
      negative pressure wound therapy had a superior improvement of a variety of
      subjective items, resulting in an overall much better satisfaction with the
      course of wound healing. Our findings suggest, that incisional negative pressure
      wound therapy seems to be a reasonable therapeutic option to reduce incidence of
      SSSIs and to have a beneficial impact to patient's quality of life, as well as,
      socio-economic aspects.

PMID- 29356191
TI  - Skeletal muscle mass in human athletes: What is the upper limit?
AB  - OBJECTIVES: To examine the amount of absolute and relative skeletal muscle mass
      (SM) in large sized athletes to investigate the potential upper limit of whole
      body muscle mass accumulation in the human body. METHODS: Ninety-five large-sized
      male athletes and 48 recreationally active males (control) had muscle thickness
      measured by ultrasound at nine sites on the anterior and posterior aspects of the
      body. SM was estimated from an ultrasound-derived prediction equation. Body
      density was estimated by hydrostatic weighing technique, and then body fat
      percentage and fat-free mass (FFM) were calculated. We used the SM index and FFM
      index to adjust for the influence of standing height (ie, divided by height
      squared). RESULTS: Ten of the athletes had more than 100 kg of FFM, including the
      largest who had 120.2 kg, while seven of the athletes had more than 50 kg of SM,
      including the largest who had 59.3 kg. FFM index and SM index were higher in
      athletes compared to controls and the percentage differences between the two
      groups were 44% and 56%, respectively. The FFM index increased linearly up to 90
      kg of body mass, and then the values leveled off in those of increasing body
      mass. Similarly, the SM index increased in a parabolic fashion reaching a plateau
      (approximately 17 kg/m2 ) beyond 120 kg body mass. CONCLUSIONS: SM index may be a
      valuable indicator for determining skeletal muscle mass in athletes. A SM index
      of approximately 17 kg/m2 may serve as the potential upper limit in humans.

PMID- 29356192
TI  - How much of Toyota's philosophy is embedded in health care at the organisational
      level? A review.
AB  - AIMS: Identify which of Toyota's principles are reported in health care
      institutions at the organisational level and to identify the type of reported
      outcomes related to the effectiveness of lean production reported in these
      studies. BACKGROUND: No scientific research has been conducted to determine which
      of Toyota's principles are embedded in health care systems. This knowledge is
      needed to perform targeted adjustments in health care. EVALUATION: Sixty studies
      were identified for the final analysis. KEY ISSUE(S): Some Toyota Way principles
      appear more deeply embedded in health care institutions than others are.
      CONCLUSION: Not all principles of Toyota's philosophy and production system were
      embedded in the studies in this review. The type of reported outcomes at the
      organisational level was diverse. IMPLICATIONS FOR NURSING MANAGEMENT: This
      literature review increases our knowledge about how many (and which) of the
      Toyota Way principles are embedded in health care. This knowledge may support
      reflection by nursing managers about how the full range of lean management
      principles could be embedded at the managerial and/or operational level.

PMID- 29356193
TI  - Nurses' perceptions of teamwork and workplace bullying.
AB  - The purpose of this study was to explore the association between nurses'
      perceptions and attitudes of teamwork and workplace bullying. A total of 128
      nurses in two hospitals in the northeast USA completed three surveys: Attitudes
      about teamwork survey, Team characteristics survey, and Negative intention
      questionnaire. A majority of nurses believed that teamwork was an important
      vehicle for providing quality patient care. Two thirds of the nurses reported the
      presence of important variables such as leadership, trust and communication on
      their teams. Despite these positive perceptions, a third of the nurses reported
      being bullied and half observed others being bullied. A number of effective team
      skills were associated with fewer occurrences of workplace bullying.

PMID- 29356195
TI  - Acute coronary syndrome of very unusual etiology.
AB  - Aortitis is one of many possible manifestations of tertiary syphilis. Aortic
      disease is the most common of all cardiovascular syphilitic lesions. Aortic
      diseases caused by tertiary syphilis include aortitis, aortic root dilation,
      aneurysm formation, aortic regurgitation and coronary ostial stenosis. A less
      common manifestation of syphilitic aortitis is coronary artery ostial narrowing
      related to aortic wall thickening. We report a case of a 40-year-old male patient
      admitted with a clinical picture of acute coronary syndrome (unstable angina). He
      had no risk factors for coronary artery disease. The physical examination
      revealed nothing remarkable. The admission electrocardiogram (ECG) showed ST
      segment depression in the anterolateral and inferior leads (Figure 1). The
      coronary angiogram showed critical ostial stenosis of the right (RCA) and left
      main coronary artery (Figure 2a, b). Cardiac-computed tomography showed aortic
      wall thickening with involvement of bilateral coronary ostia (Figure 2b, c). The
      patient was referred for coronary bypass surgery after treatment with two doses
      of penicillin G. The laboratory test was strongly positive for syphilitic
      infection. Postoperative treatment with benzathine penicillin, in doses
      recommended for tertiary syphilis, was implemented.

PMID- 29356194
TI  - A quantification of the alcohol use-consequences association in college student
      and clinical populations: A large, multi-sample study.
AB  - BACKGROUND: The present study sought to quantify the relationship between alcohol
      use and alcohol-related consequences in both college student and clinical
      samples. METHODS: We gathered 33 college student datasets comprising of 15,618
      participants and nine clinical sample datasets comprising of 4,527 participants
      to determine the effect size of the relationship between alcohol use and alcohol
      related consequences. We used random-effects meta-analytic techniques, separately
      in college and clinical samples, to account for a distribution of true effects
      and to assess for heterogeneity in effect sizes. RESULTS: Results demonstrated
      that the clear majority of the variability in alcohol-related consequences is not
      explained by alcohol use (ie, >77% in college samples; >86% in clinical samples),
      and that there was significant heterogeneity in all effect sizes. CONCLUSIONS AND
      SCIENTIFIC SIGNIFICANCE: Experiencing alcohol-related consequences results from
      factors that extend beyond frequency and quantity of alcohol consumed suggesting
      a need to examine other predictors of alcohol-related consequences beyond alcohol
      use. (Am J Addict 2018;27:116-123).

PMID- 29356196
TI  - Complexes of Stiboranium Mono-, Di-, and Trications.
AB  - Reaction of Ph2 SbCl3 with 2,2'-bipyridine and Me3 SiOSO2 CF3 releases
      chlorobenzene, which is interpreted as a reductive (SbV /SbIII ) elimination from
      a complex of a stiboranium cation. Conversely, reactions of Ph2 SbCl3 with 4
      methylpyridine-N-oxide and AgOSO2 CF3 give redox-resistant complexes with the
      generic formulae [Ph2 SbCl3-x Lx+1 ][OTf]x , including a compound containing a
      pnictogen(V) trication.

PMID- 29356197
TI  - Reference values and changes in infant sleep-wake behaviour during the first 12
      months of life: a systematic review.
AB  - This paper is a systematic review on the reference values and changes in infant
      sleep-wake behaviour during the first 12 months of life. This systematic review
      was conducted according to the Preferred Reporting Items for Systematic Reviews
      and Meta-Analysis (PRISMA). Seventy-four papers were included, and the reference
      values and changes in sleep-wake behaviour during the first 12 months of life
      were identified. Sleep duration during the 24-h period, and day and sleep periods
      during the night decreased over the first 12 months of life. Night wakings and
      bedtime/sleep-onset time decreased, while the longest sleep period increased at
      night during the first 6 months. High discrepancy was noted between studies in
      the reference values of sleep-wake behaviour, while more congruence was noted
      regarding changes, especially those occurring in the first 6 months of life.
      Several methodological differences were identified between studies and may
      partially explain inconsistencies in the results, including the assessment of
      different sleep-wake behaviours, the focus on specific ages or age ranges, the
      use of self-report, observational or direct measures, the recruitment of small or
      large representative samples, and the countries where the research was conducted.
      These aspects should be considered in future research and caution should be taken
      when generalizing results from studies with diverse methodological
      characteristics. Nonetheless, this review identifies normative reference values
      and the changes occurring in infant sleep-wake behaviour, and could inform both
      practitioners and researchers, helping them identify infants with sleep delays or
      problems.

PMID- 29356198
TI  - Defective XRN3-mediated transcription termination in Arabidopsis affects the
      expression of protein-coding genes.
AB  - Arabidopsis thaliana contains two nuclear XRN2/3 5'-3' exonucleases that are
      homologs of yeast and human Rat1/Xrn2 proteins involved in the processing and
      degradation of several classes of nuclear RNAs and in transcription termination
      of RNA polymerase II. Using strand-specific short read sequencing we show that
      knockdown of XRN3 leads to an altered expression of hundreds of genes and the
      accumulation of uncapped and polyadenylated read-through transcripts generated by
      inefficiently terminated Pol II. Our data support the notion that XRN3-mediated
      changes in the expression of a subset of genes are caused by upstream read
      through transcription and these effects are enhanced by RNA-mRNA chimeras
      generated in xrn3 plants. In turn, read-through transcripts that are antisense to
      downstream genes may trigger production of siRNA. Our results highlight the
      importance of XRN3 exoribonuclease in Pol II transcription termination in plants
      and show that disturbance in this process may significantly alter gene
      expression.

PMID- 29356199
TI  - Disulfide-Linked Dendritic Oligomeric Phthalocyanines as Glutathione-Responsive
      Photosensitizers for Photodynamic Therapy.
AB  - A series of disulfide-linked dendritic phthalocyanines were synthesized by using
      the CuI -catalyzed alkyne-azide cycloaddition reaction as the key step. Whereas
      these compounds were essentially nonaggregated in N,N-dimethylformamide, they
      were stacked in citrate solution (pH 7.4, with 1 % Cremophor EL), as shown by the
      broad appearance of their Q-band absorption. Having two-to-six zinc(II)
      phthalocyanine units in a molecule, these compounds were significantly self
      quenched, particularly in citrate solution. Both the fluorescence intensity and
      singlet-oxygen generation efficiency were significantly lower than those of the
      monomeric counterparts, and the self-quenching efficiency increased as the number
      of phthalocyanine units increased. Upon interaction with 5 mm glutathione (GSH)
      in citrate solution, the fluorescence intensity of these compounds increased as a
      result of cleavage of the disulfide linkages and separation of the phthalocyanine
      units, which thereby reduced the self-quenching effect. The "on/off" ratios were
      found to be 7, 18, 23, and 21 for the dimeric (PC2), trimeric (PC3), tetrameric
      (PC4), and hexameric (PC6) systems, respectively. GSH also enhanced the
      fluorescence emission inside human colon adenocarcinoma HT29 cells and promoted
      the formation of singlet oxygen of these compounds. Upon irradiation, their half
      maximal inhibitory concentration (IC50 ) values were found to be in the range of
      0.18 to 0.38 MUm. Finally, the biodistribution and activation of PC2 and PC6 were
      also examined in HT29 tumor-bearing nude mice. For both compounds, the
      fluorescence intensity per unit area at the tumor was found to grow gradually
      during the first 24 h. Whereas the intensity then dropped for PC2, the intensity
      for PC6 remained steady over the following 6 d, which might have been a result of
      the enhanced permeability and retention effect arising from the larger molecular
      mass of the hexameric system.

PMID- 29356200
TI  - Cutaneous melioidosis: two cases of chronic primary forms.

PMID- 29356201
TI  - Novel method to save the parathyroid gland during thyroidectomy: Subcapsular
      saline injection.
AB  - BACKGROUND: Saving the parathyroid gland during thyroidectomy remains
      challenging. Subcapsular saline injection (SCASI) was developed in February 2015.
      Its ability to spare the parathyroid gland was assessed. METHODS: All consecutive
      patients who underwent total thyroidectomy with or without neck lymph node
      dissection in 2013-2015 were included in this retrospective cohort study.
      Patients were divided into the SCASI and non-SCASI groups. Serum parathyroid
      hormone (PTH) levels were measured on day 1 and 6 months after surgery. Transient
      and permanent hypoparathyroidism were defined as day 1 and 6 month PTH < 10.0 and
      <15.0 pg/mL, respectively. RESULTS: The groups (both had 98 patients each) did
      not differ in demographics, tumor size, operation extent, pathology, thyroiditis
      rate, and incidental parathyroid gland excision rate. Compared with non-SCASI
      patients, patients who underwent the SCASI method exhibited transient
      hypoparathyroidism (35.7% vs 19.4%, P < .001) and permanent hypoparathyroidism
      (4.1% vs 0%, P = .043) significantly less frequently. CONCLUSION: The procedure
      of SCASI effectively spared the parathyroid gland during thyroidectomy.

PMID- 29356202
TI  - Nurses' satisfaction with use of a personal digital assistants with a mobile
      nursing information system in China.
AB  - BACKGROUND: Personal digital assistants, technology with various functions, have
      been applied in international clinical practice. Great benefits in reducing
      medical errors and enhancing the efficiency of clinical work have been achieved,
      but little research has investigated nurses' satisfaction with the use of
      personal digital assistants. AIM: To investigate nurses' satisfaction with use of
      personal digital assistants, and to explore the predictors of this. DESIGN: This
      is a cross-sectional descriptive study. METHODS: We conducted a cross-sectional
      survey targeting nurses who used personal digital assistants in a comprehensive
      tertiary hospital in Beijing. RESULTS: A total of 383 nurses were recruited in
      this survey in 2015. The total score of nurses' satisfaction with use of personal
      digital assistants was 238.91 (SD 39.25). Nurses were less satisfied with the
      function of documentation, compared with the function of administering medical
      orders. The time length of using personal digital assistants, academic degree,
      and different departments predicted nurses' satisfaction towards personal digital
      assistant use (all P < 0.05). CONCLUSION: Nurses were satisfied with the accuracy
      of administering medical orders and the safety of recording data. The stability
      of the wireless network and efficiency related to nursing work were less
      promising. To some extent, nurses with higher education and longer working time
      with personal digital assistants were more satisfied with them.

PMID- 29356203
TI  - Crystal Field in Rare-Earth Complexes: From Electrostatics to Bonding.
AB  - The flexibility of first-principles (ab initio) calculations with the SO-CASSCF
      (complete active space self-consistent field theory with a treatment of the spin
      orbit (SO) coupling by state interaction) method is used to quantify the
      electrostatic and covalent contributions to crystal field parameters. Two types
      of systems are chosen for illustration: 1) The ionic and experimentally well
      characterized PrCl3 crystal; this study permits a revisitation of the partition
      of contributions proposed in the early days of crystal field theory; and 2) a
      series of sandwich molecules [Ln(etan -Cn Hn )2 ]q , with Ln=Dy, Ho, Er, and Tm
      and n=5, 6, and 8, in which the interaction between LnIII and the aromatic
      ligands is more difficult to describe within an electrostatic approach. It is
      shown that a model with three layers of charges reproduces the electrostatic
      field generated by the ligands and that the covalency plays a qualitative role.
      The one-electron character of crystal field theory is discussed and shown to be
      valuable, although it is not completely quantitative. This permits a reduction of
      the many-electron problem to a discussion of the energy of the seven 4f orbitals.

PMID- 29356204
TI  - Robotic surgery for submandibular gland resection through a trans-hairline
      approach: The first human series and comparison with applicable approaches.
AB  - BACKGROUND: Many submandibular gland diseases are treated by surgical
      intervention. Transcervical surgery results in an obvious cervical scar, whereas
      the retroauricular approach leaves a scar in the postauricular area. Therefore,
      robotic submandibular gland resection through a trans-hairline approach is
      developed to improve postoperative aesthetic outcomes. METHODS: From 2012 to
      2017, 24 consecutive patients who met the inclusion criteria and had received
      submandibular gland resection through the trans-hairline robotic surgery were
      analyzed. RESULTS: All surgical procedures were successfully performed without
      conversion and appreciable complications. The incision was completely concealed
      within the hairs. Treatments of submandibular gland benign or malignant tumors
      were completed without any positive margins or disease recurrence. CONCLUSION:
      This study demonstrated the feasibility and safety of the trans-hairline approach
      for robotic submandibular gland resection in the first human series. The
      procedure is applicable to many submandibular gland diseases with complete
      disease control, and has aesthetic advantages over other robotic surgical
      approaches.

PMID- 29356205
TI  - Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis,
      and coxsackievirus: A systematic review.
AB  - Viral infections are being managed therapeutically through available antiviral
      regimens with unsatisfactory clinical outcomes. The refractory viral infections
      resistant to available antiviral drugs are alarming threats and a serious health
      concern. For viral hepatitis, the interferon and vaccine therapies solely are not
      ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing
      incidences of viral infections and especially of resistant viral strains, the
      available therapeutic modalities need to be improved, complemented with the
      discovery of novel antiviral agents to combat refractory viral infections. It is
      widely accepted that medicinal plant heritage is nature gifted, precious, and
      fueled with the valuable resources for treatment of metabolic and infectious
      disorders. The aims of this review are to assemble the facts and to conclude the
      therapeutic potential of medicinal plants in the eradication and management of
      various viral diseases such as influenza, human immunodeficiency virus (HIV),
      herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have
      been proven in diverse clinical studies. The articles, published in the English
      language since 1982 to 2017, were included from Web of Science, Cochrane Library,
      AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords
      including plants possessing antiviral activity, the antiviral effects of plants,
      and plants used in viral disorders. The scientific literature mainly focusing on
      plant extracts and herbal products with therapeutic efficacies against
      experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were
      included in the study. Pure compounds possessing antiviral activity were
      excluded, and plants possessing activity against viruses other than viruses in
      inclusion criteria were excluded. Hundreds of plant extracts with antiviral
      effect were recognized. However, the data from only 36 families investigated
      through in vitro and in vivo studies met the inclusion criteria of this review.
      The inferences from scientific literature review, focusing on potential
      therapeutic consequences of medicinal plants on experimental models of HIV, HSV,
      influenza, hepatitis, and coxsackievirus have ascertained the curative antiviral
      potential of plants. Fifty-four medicinal plants belonging to 36 different
      families having antiviral potential were documented. Out of 54 plants, 27
      individually belong to particular plant families. On the basis of the work of
      several independent research groups, the therapeutic potential of medicinal
      plants against listed common viral diseases in the region has been proclaimed. In
      this context, the herbal formulations as alternative medicine may contribute to
      the eradication of complicated viral infection significantly. The current review
      consolidates the data of the various medicinal plants, those are Sambucus nigra,
      Caesalpinia pulcherrima, and Hypericum connatum, holding promising specific
      antiviral activities scientifically proven through studies on experimental animal
      models. Consequently, the original research addressing the development of novel
      nutraceuticals based on listed medicinal plants is highly recommended for the
      management of viral disorders.

PMID- 29356206
TI  - Survey of diagnostic and treatment practices for multiple sclerosis (MS) in
      Europe. Part 2: Progressive MS, paediatric MS, pregnancy and general management.
AB  - BACKGROUND AND PURPOSE: The European Charcot Foundation supported the development
      of a set of surveys to understand current practice patterns for the diagnosis and
      management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes
      survey results related to secondary progressive MS (SPMS), primary progressive MS
      (PPMS), pregnancy, paediatric MS and overall patient management. METHODS: A
      steering committee of MS neurologists developed case- and practice-based
      questions for two sequential surveys distributed to MS neurologists throughout
      Europe. RESULTS: Respondents generally favoured changing rather than stopping
      disease-modifying treatment (DMT) in patients transitioning from relapsing
      remitting MS to SPMS, particularly with active disease. Respondents would not
      initiate DMT in patients with typical PPMS symptoms, although the presence of >=1
      spinal cord or brain gadolinium-enhancing lesion might affect that decision. For
      patients considering pregnancy, respondents were equally divided on whether to
      stop treatment before or after conception. Respondents strongly favoured starting
      DMT in paediatric MS with active disease; recommended treatments included
      interferon, glatiramer acetate and, in John Cunningham virus negative patients,
      natalizumab. Additional results regarding practice-based questions and management
      are summarized. CONCLUSIONS: Results of part 2 of the survey of diagnostic and
      treatment practices for MS in Europe largely mirror results for part 1, with
      neurologists in general agreement about the treatment and management of SPMS,
      PPMS, pregnancy and paediatric MS as well as the general management of MS.
      However, there are also many areas of disagreement, indicating the need for
      evidence-based recommendations and/or guidelines.

PMID- 29356207
TI  - Mexiletine or catheter ablation after amiodarone failure in the VANISH trial.
AB  - INTRODUCTION: In patients with ischemic heart disease and ventricular tachycardia
      (VT) refractory to high dose amiodarone, the two most common therapeutic options
      are adjunctive mexiletine therapy or catheter ablation. There are little existing
      data on the efficacy of these strategies. We examined the relative efficacy of
      adjunctive mexiletine and catheter ablation among patients enrolled in the VANISH
      trial. METHODS: All subjects enrolled in the VANISH trial who had VT refractory
      to high dose (>= 300 mg daily) amiodarone at baseline were included. Per
      protocol, subjects randomized to escalated drug therapy received adjunctive
      mexiletine. RESULTS: Nineteen of the 259 patients were receiving high-dose
      amiodarone at baseline and 11 were randomized to escalated therapy with
      mexiletine and 8 to ablation. The adjunctive mexiletine group had a higher rate
      of the primary composite outcome (death, VT storm, or appropriate shock) in
      comparison to catheter ablation (HR 6.87 [2.08-22.8]). Over 90% of the patients
      in the adjunctive mexiletine/group experienced a primary endpoint during a median
      9.2 months' follow-up. There was no difference in the rate of adverse events
      between the two groups. CONCLUSIONS: Mexiletine has limited efficacy in the
      treatment of recurrent VT despite high-dose amiodarone therapy, in patients with
      ischemic heart disease. Catheter ablation is a superior strategy in this
      population.

PMID- 29356208
TI  - Improving recruitment to pharmacological trials for illicit opioid use: findings
      from a qualitative focus group study.
AB  - AIM: To explore potential study participants' views on willingness to join
      clinical trials of pharmacological interventions for illicit opioid use to inform
      and improve future recruitment strategies. DESIGN: Qualitative focus group study
      [six groups: oral methadone (two groups); buprenorphine tablets (two groups);
      injectable opioid agonist treatment (one group); and former opioid agonist
      treatment (one group)]. SETTINGS: Drug and alcohol services and a peer support
      recovery service (London, UK). PARTICIPANTS: Forty people with experience of
      opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66
      years). MEASUREMENTS: Data collection was facilitated by a topic guide that
      explored willingness to enrol in clinical pharmacological trials. Groups were
      audio-recorded and transcribed. Transcribed data were analysed inductively via
      Iterative Categorization. FINDINGS: Participants' willingness to join
      pharmacological trials of medications for opioid dependence was affected by
      factors relating to study burden, study drug, study design, study population and
      study relationships. Participants worried that the trial drug might be worse
      than, or interfere with, their current treatment. They also misunderstood aspects
      of trial design despite the researchers' explanations. CONCLUSIONS: Recruitment
      of participants for clinical trials of pharmacological interventions for illicit
      opioid use could be improved if researchers became better at explaining clinical
      trials to potential participants, dispelling misconceptions about trials and
      increasing trust in the research process and research establishment. A checklist
      of issues to consider when designing pharmacological trials for illicit opioid
      use is proposed.

PMID- 29356209
TI  - Multicenter assessment of exclusive endoscopic endonasal approach for the
      treatment of 53 olfactory neuroblastomas.
AB  - BACKGROUND: Given the particularities of olfactory neuroblastoma (ONB) and the
      lack of studies on the subject, a multicenter collaborative study was conducted
      to assess treatment strategy. METHODS: Fifty-three patients with ONB were
      included from the French Rare Head and Neck Cancer Expert Network (REFCOR)
      database: 16T1, 8T2, 19T3, and 10T4. All cases were treated endoscopically with
      skull base removal and repair in 26 cases (49%) and without external craniotomy.
      RESULTS: The overall survival (OS) and disease-free survival (DFS) rates at 5
      years were 87% and 71%, respectively, with mean follow-up of 45.4 +/- 26.5
      months. The complication rate was 18.8% with 4 cases of meningitis. Pathological
      analysis showed positive margins in 26.8%, notably on the dura-mater and
      periorbita, without impairment of OS or DFS. Forty-eight patients received
      adjuvant radiotherapy on T +/- N. Ten patients had a recurrence (18.9%). Six
      patients died of their disease. Prophylactic neck irradiation seemed to reduce
      the recurrence rate. CONCLUSION: Exclusively endoscopic treatment proved
      efficient and reliable in a large controlled series.

PMID- 29356210
TI  - Clinical course and prognostic factors across different musculoskeletal pain
      sites: A secondary analysis of individual patient data from randomised clinical
      trials.
AB  - BACKGROUND: Previous research has identified similar prognostic factors in
      patients with musculoskeletal (MSK) conditions regardless of pain presentation,
      generating opportunities for management based on prognosis rather than specific
      pain presentation. METHODS: Data from seven RCTs (2483 participants) evaluating a
      range of primary care interventions for different MSK pain conditions were used
      to investigate the course of symptoms and explore similarities and differences in
      predictors of outcome. The value of pain site for predicting changes in pain and
      function was investigated and compared with that of age, gender, social class,
      pain duration, widespread pain and level of anxiety/depression. RESULTS: Over the
      initial three months of follow-up, changes in mean pain intensity reflected an
      improvement, with little change occurring after this period. Participants with
      knee pain due to osteoarthritis (OA) showed poorer long-term outcome (mean
      difference in pain reduction at 12 months -1.85, 95% CI -2.12 to -1.57, compared
      to low back pain). Increasing age, manual work, longer pain duration, widespread
      pain and increasing anxiety/depression scores were significantly associated with
      poorer outcome regardless of pain site. Testing of interactions showed some
      variation between pain sites, particularly for knee OA, where age, manual work
      and pain duration were most strongly associated with outcome. CONCLUSIONS:
      Despite some differences in prognostic factors for trial participants with knee
      OA who were older and had more chronic conditions, similarity of outcome
      predictors across regional MSK pain sites provides evidence to support targeting
      of treatment based on prognostic factors rather than site of pain. SIGNIFICANCE:
      Individual patient data analysis of trials across different regional
      musculoskeletal pain sites was used to evaluate course and prognostic factors
      associated with pain and disability. Overall, similarity of outcome predictors
      across these different pain sites supports targeting of treatment based on
      prognostic factors rather than pain site alone.

PMID- 29356211
TI  - Impact of anti-HCV direct antiviral agents on graft function and
      immunosuppressive drug levels in kidney transplant recipients: a call to
      attention in the mid-term follow-up in a single-center cohort study.
AB  - The medium-term impact on graft function and immunosuppressive drug
      pharmacokinetics of direct antiviral agents (DAAs) among hepatitis C virus (HCV)
      infected kidney transplant (KT) recipients remain unclear. We compared pre- and
      post-treatment 12-month trajectories of estimated glomerular filtration rate
      (DeltaeGFR) and 24-h proteinuria (Delta24-h proteinuria) in 49 recipients treated
      with DAAs (mostly sofosbuvir plus ledipasvir). Among evaluable patients, 66.7%
      and 100.0% had undetectable viral load by week 4 and end of therapy (EoT). The
      sustained virologic response rate at 12 weeks was 95.8%. Overall, 80.6% of
      patients receiving tacrolimus required dose escalation while on DAA-based therapy
      (median increase of 66.7%) to maintain target levels. Tacrolimus levels resulted
      to be higher at 12 months compared to EoT (7.8 +/- 2.1 vs. 6.7 +/- 2.0 ng/ml; P
      value = 0.002). No changes in graft function during the course of therapy were
      observed. However, eGFR significantly decreased (P-value <0.001) throughout the
      first 12 months after EoT. Median DeltaeGFR and Delta24-h over pre- and post
      treatment periods were 3.9% and -6.1% (P-value = 0.002) and -5.3% and 26.2% (P
      value = 0.057). Caution should be exercised when adjusting immunosuppression in
      HCV-infected KT recipients upon initiation of DAAs, followed by mid-term
      monitoring of immunosuppressive drug levels and graft function.

PMID- 29356212
TI  - Emerging Strategies of Cancer Therapy Based on Ferroptosis.
AB  - Ferroptosis, a new form of regulated cell death that is iron- and reactive oxygen
      species dependent, has attracted much attention in the research communities of
      biochemistry, oncology, and especially material sciences. Since the first
      demonstration in 2012, a series of strategies have been developed to induce
      ferroptosis of cancer cells, including the use of nanomaterials, clinical drugs,
      experimental compounds, and genes. A plethora of research work has outlined the
      blueprint of ferroptosis as a new option for cancer therapy. However, the
      published ferroptosis-related reviews have mainly focused on the mechanisms and
      pathways of ferroptosis, which motivated this contribution to bridge the gap
      between biological significance and material design. Therefore, it is timely to
      summarize the previous efforts on the emerging strategies for inducing
      ferroptosis and shed light on future directions for using such a tool to fight
      against cancer. Here, the current strategies of cancer therapy based on
      ferroptosis will be elaborated, the design considerations and the advantages and
      limitations are highlighted, and finally a future perspective on this emerging
      field is given.

PMID- 29356213
TI  - A multi-parent advanced generation inter-cross (MAGIC) population for genetic
      analysis and improvement of cowpea (Vigna unguiculata L. Walp.).
AB  - Multi-parent advanced generation inter-cross (MAGIC) populations are an emerging
      type of resource for dissecting the genetic structure of traits and improving
      breeding populations. We developed a MAGIC population for cowpea (Vigna
      unguiculata L. Walp.) from eight founder parents. These founders were genetically
      diverse and carried many abiotic and biotic stress resistance, seed quality and
      agronomic traits relevant to cowpea improvement in the United States and sub
      Saharan Africa, where cowpea is vitally important in the human diet and local
      economies. The eight parents were inter-crossed using structured matings to
      ensure that the population would have balanced representation from each parent,
      followed by single-seed descent, resulting in 305 F8 recombinant inbred lines
      each carrying a mosaic of genome blocks contributed by all founders. This was
      confirmed by single nucleotide polymorphism genotyping with the Illumina Cowpea
      Consortium Array. These lines were on average 99.74% homozygous but also diverse
      in agronomic traits across environments. Quantitative trait loci (QTLs) were
      identified for several parental traits. Loci with major effects on photoperiod
      sensitivity and seed size were also verified by biparental genetic mapping. The
      recombination events were concentrated in telomeric regions. Due to its broad
      genetic base, this cowpea MAGIC population promises breakthroughs in genetic
      gain, QTL and gene discovery, enhancement of breeding populations and, for some
      lines, direct releases as new varieties.

PMID- 29356214
TI  - Sub-threshold transcranial magnetic stimulation applied after the go-signal
      facilitates reaction time under control but not startle conditions.
AB  - The presentation of a startling acoustic stimulus (SAS) in a simple reaction time
      (RT) task significantly reduces RT due to the involuntary early initiation of a
      prepared movement; however, the underlying neural mechanism remains unclear. It
      has been proposed that a SAS triggers a cortically stored motor program by
      involuntarily increasing initiation-related activation. Sub-threshold
      transcranial magnetic stimulation (TMS) can be used to investigate cortical
      processes, as it increases cortical excitability for 6-30 ms and significantly
      reduces RT. The purpose of the present experiments was to determine whether the
      application of sub-threshold TMS over motor cortex in close temporal proximity to
      a SAS would facilitate startle RT in the same manner as control RT, providing
      evidence for cortical involvement in startle-related RTs. Participants completed
      a simple RT task requiring targeted wrist extension in response to an auditory go
      signal, which was randomly replaced by a SAS on 25% of trials. On a subset of
      trials, sub-threshold TMS was applied 30 ms following the go-signal in control
      trials or at -15, 0, +15 or +30 ms with respect to the SAS in startle trials. In
      all three experiments, sham and real TMS significantly reduced RT in control
      trials, with real TMS having a larger effect, but there was no effect of either
      real or sham TMS on startle-related RT. These results suggest that there may be
      limited cortical involvement in the initiation of movements in response to a SAS.
      As an alternative, startle may produce the fastest possible RTs, with little room
      for additional facilitation.

PMID- 29356215
TI  - Appearance-based interventions to reduce UV exposure: A systematic review.
AB  - PURPOSE: As a majority of skin cancer cases are behaviourally preventable, it is
      crucial to develop effective strategies to reduce UV exposure. Health-focused
      interventions have not proved to be sufficiently effective, and it has been
      suggested that people might be more susceptible to information about the negative
      effects of the sun on their appearance. METHOD: This systematic review of 30
      separate papers, reporting 33 individual studies published between 2005 and 2017,
      assesses the overall effectiveness of appearance interventions on participants'
      UV exposure and sun protection behaviour. RESULTS: Appearance-based interventions
      have positive effects on sun exposure and sun protection, immediately after the
      intervention as well as up to 12 months afterwards. The meta-analysis found a
      medium effect size on sun protection intentions for interventions which combined
      UV photography and photoageing information: r+  = .424; k = 3, N = 319, CI =
      0.279-0.568, p = .023. CONCLUSIONS: This review provides a current perspective on
      the effectiveness of appearance-based interventions to reduce UV exposure, and
      also highlights methodological issues. It recommends that practitioners
      administer a UV photo intervention in combination with photoageing information to
      reduce UV exposure. Furthermore, the review specifically recommends that future
      research focuses on the use of theoretical constructs to enhance photoageing
      information and is conducted with older participants and in countries where
      people have less opportunity for sun exposure. Statement of contribution What is
      already known on this subject? Appearance-focused interventions may in some cases
      be more effective than health-focused interventions in reducing UV exposure, as
      the underlying motivations for tanning are associated with appearance concerns.
      Previous reviews and meta-analyses have indicated that appearance-focused
      interventions such as photoageing and UV photo are associated with positive
      effects in reducing UV exposure and/or increasing sun protection. Previous
      reviews identified methodological issues with research on this topic, which
      included limited a priori power calculations and a general lack of long-term
      follow-ups. What does this study add? This review concludes that photoageing
      information in combination with UV photo is associated with a medium positive
      effect size on sun protection intentions. Photoageing can be manipulated
      according to theoretical constructs (e.g., Theory of Alternative Behaviours),
      which may contribute to its effectiveness. Issues such as homogeneity of settings
      and participants and limited a priori power calculations in the included studies
      have been identified. This review specifically recommends that future research is
      conducted in locations with less overall sun exposure, and with a more diverse
      participant range (e.g., more males and older participants).

PMID- 29356217
TI  - Cleft nipple: A rare congenital breast anomaly.

PMID- 29356218
TI  - Brain oxygenation with a non-vasoactive perfluorocarbon emulsion in a rat model
      of traumatic brain injury.
AB  - OBJECTIVE: The aim of this study was to assess, in two experiments, the safety
      and efficacy of the PFC emulsion Oxycyte as an oxygen therapeutic for TBI to test
      the hypothesis that early administration of this oxygen-carrying fluid post-TBI
      would improve brain tissue oxygenation (Pbt O2 ). METHODS: The first experiment
      assessed the effects of Oxycyte on cerebral vasoactivity in healthy, uninjured
      rats using intravital microscopy. The second experiment investigated the effect
      of Oxycyte on cerebral Pbt O2 using the PQM in TBI model. Animals in the Oxycyte
      group received a single injection of Oxycyte (6 mL/kg) shortly after TBI, while
      NON animals received no treatment. RESULTS: Oxycyte did not cause
      vasoconstriction in small- (<50 MUm) or medium- (50-100 MUm) sized pial
      arterioles nor did it cause a significant change in blood pressure. Treatment
      with Oxycyte while breathing 100% O2 did not improve Pbt O2 . However, in rats
      ventilated with ~40% O2 , Pbt O2 improved to near pre-TBI values within 105
      minutes after Oxycyte injection. CONCLUSIONS: Although Oxycyte did not cause
      cerebral vasoconstriction, its use at the dose tested while breathing 100% O2 did
      not improve Pbt O2 following TBI. However, Oxycyte treatment while breathing a
      lower enriched oxygen concentration may improve Pbt O2 after TBI.

PMID- 29356216
TI  - Treatment gap for anxiety disorders is global: Results of the World Mental Health
      Surveys in 21 countries.
AB  - BACKGROUND: Anxiety disorders are a major cause of burden of disease. Treatment
      gaps have been described, but a worldwide evaluation is lacking. We estimated,
      among individuals with a 12-month DSM-IV (where DSM is Diagnostic Statistical
      Manual) anxiety disorder in 21 countries, the proportion who (i) perceived a need
      for treatment; (ii) received any treatment; and (iii) received possibly adequate
      treatment. METHODS: Data from 23 community surveys in 21 countries of the World
      Mental Health (WMH) surveys. DSM-IV mental disorders were assessed (WHO Composite
      International Diagnostic Interview, CIDI 3.0). DSM-IV included posttraumatic
      stress disorder among anxiety disorders, while it is not considered so in the DSM
      5. We asked if, in the previous 12 months, respondents felt they needed
      professional treatment and if they obtained professional treatment
      (specialized/general medical, complementary alternative medical, or nonmedical
      professional) for "problems with emotions, nerves, mental health, or use of
      alcohol or drugs." Possibly adequate treatment was defined as receiving
      pharmacotherapy (1+ months of medication and 4+ visits to a medical doctor) or
      psychotherapy, complementary alternative medicine or nonmedical care (8+ visits).
      RESULTS: Of 51,547 respondents (response = 71.3%), 9.8% had a 12-month DSM-IV
      anxiety disorder, 27.6% of whom received any treatment, and only 9.8% received
      possibly adequate treatment. Of those with 12-month anxiety only 41.3% perceived
      a need for care. Lower treatment levels were found for lower income countries.
      CONCLUSIONS: Low levels of service use and a high proportion of those receiving
      services not meeting adequacy standards for anxiety disorders exist worldwide.
      Results suggest the need for improving recognition of anxiety disorders and the
      quality of treatment.

PMID- 29356220
TI  - Comparison of false-negative rates and limits of detection following macrofoam
      swab sampling of Bacillus anthracis surrogates via Rapid Viability PCR and plate
      culture.
AB  - AIMS: We evaluated the effects of Bacillus anthracis surrogates, low surface
      concentrations, surface materials and assay methods on false-negative rate (FNR)
      and limit of detection (LOD95 ) for recovering Bacillus spores using a macrofoam
      swab sampling procedure. METHODS AND RESULTS: Bacillus anthracis Sterne or
      Bacillus atrophaeus Nakamura spores were deposited over a range of low target
      concentrations (2-500 per coupon) onto glass, stainless steel, vinyl tile and
      plastic. Samples were assayed using a modified Rapid Viability-PCR (mRV-PCR)
      method and the traditional plate culture method to obtain FNR and LOD95 results.
      CONCLUSIONS: Mean FNRs tended to be lower for mRV-PCR compared to culturing, and
      increased as spore concentration decreased for all surface materials. Surface
      material, but not B. anthracis surrogate, influenced FNRs with the mRV-PCR
      method. The mRV-PCR LOD95 was lowest for glass and highest for vinyl tile. LOD95
      values overall were lower for mRV-PCR than for the culture method. SIGNIFICANCE
      AND IMPACT OF STUDY: This study adds to the limited data on FNR and LOD95 for mRV
      PCR and culturing methods with low concentrations of B. anthracis sampled from
      various surface materials by the CDC macrofoam-swab method. These are key inputs
      for planning characterization and clearance studies for low contamination levels
      of B. anthracis.

PMID- 29356219
TI  - Psychometric properties of the Dutch extended Cancer Survivors' Unmet Needs
      measure (CaSUN-NL).
AB  - Information and support needs increase emotional distress and can impede cancer
      survivors' adjustment. To investigate the information and support needs of Dutch
      cancer survivors, the Cancer Survivors' Unmet Needs measure (CaSUN) was
      translated into Dutch and applied in two Dutch studies with cancer survivors (N =
      255; N = 467). The CaSUN-NL entailed the original five CaSUN scales, extended
      with respectively a returning to work and lifestyle scale. This study aimed to
      determine the psychometric properties of the CaSUN-NL. To assess validity, a
      maximum likelihood factor analysis was employed. Construct validity was analysed
      using Pearson's and Spearman's correlation coefficients. To assess reliability,
      test-retest (Kappa coefficient) and internal consistency (Cronbach's alpha)
      values were determined. Factor analysis revealed the original five factors. Test
      retest reliability was low (r <= .15, 93% retest response). Internal consistency
      values were high (Cronbach's alpha = 0.92-0.94), except for lifestyle.
      Significant correlations were found between total number of unmet needs with
      anxiety (r = .55), depression (r = .49), negative adjustment (r = .50), quality
      of life (r = -.52) and age (r = -.24). The CaSUN-NL is valid and reliable to
      investigate the unmet information and support needs of Dutch cancer survivors.

PMID- 29356221
TI  - Results of early treatment for de novo donor-specific antibodies in pediatric
      kidney transplant recipients in a cross-sectional and longitudinal cohort.
AB  - The development of dnDSA anti-HLA antibodies has been shown to be a significant
      risk factor for graft failure. In 2008, we instituted a routine protocol of
      standardized monitoring and treatment of dnDSA in pediatric kidney transplant
      recipients. Of 67 first-time pediatric kidney transplant recipients, 26 (38%)
      developed dnDSA after 1.36 (IQ 1-2.14) years. Coefficient of variance of
      tacrolimus, a surrogate marker of non-adherence, was found to be the single most
      important risk factor for dnDSA development. Overall, there was a significant
      reduction in dnDSA with treatment in 19 (76%) children. No difference in graft
      survival and estimated glomerular filtration rate was noted between dnDSA
      negative and those treated for dnDSA. There was an increased risk of
      hospitalization in those treated for dnDSA. This study suggests that early
      detection and treatment of dnDSA can help to prevent graft failure and preserve
      graft function in the short term. Future studies and longer follow-up are needed
      to fully elucidate the effect of early detection and treatment of dnDSA in
      pediatric kidney transplant recipients.

PMID- 29356222
TI  - Lack of ACTPK1, an STY kinase, enhances ammonium uptake and use, and promotes
      growth of rice seedlings under sufficient external ammonium.
AB  - Ammonium influx into plant roots via the high-affinity transport system (HATS) is
      down-modulated under elevated external ammonium, preventing ammonium toxicity. In
      ammonium-fed Arabidopsis, ammonium transporter 1 (AMT1) trimers responsible for
      HATS activity are allosterically inactivated in a dose-dependent manner via
      phosphorylation of the conserved threonine at the carboxyl-tail by the
      calcineurin B-like protein 1-calcineurin B-like protein-interacting protein
      kinase 23 complex and other yet unidentified protein kinases. Using transcriptome
      and reverse genetics in ammonium-preferring rice, we revealed the role of the
      serine/threonine/tyrosine protein kinase gene OsACTPK1 in down-modulation of HATS
      under sufficient ammonium. In wild-type roots, ACTPK1 mRNA and protein
      accumulated dose-dependently under sufficient ammonium. To determine the function
      of ACTPK1, two independent mutants lacking ACTPK1 were produced by
      retrotransposon Tos17 insertion. Compared with segregants lacking insertions, the
      two mutants showed decreased root growth and increased shoot growth under 1 mm
      ammonium due to enhanced ammonium acquisition, via aberrantly high HATS activity,
      and use. Furthermore, introduction of OsACTPK1 cDNA fused to the synthetic green
      fluorescence protein under its own promoter complemented growth and the HATS
      influx, and suggested plasma membrane localization. Root cellular expression of
      OsACTPK1 also overlapped with that of ammonium-induced OsAMT1;1 and OsAMT1;2.
      Meanwhile, threonine-phosphorylated AMT1 levels were substantially decreased in
      roots of ACTPK1-deficient mutants grown under sufficient ammonium. Bimolecular
      fluorescence complementation assay further confirmed interaction between ACTPK1
      and AMT1;2 at the cell plasma membrane. Overall, these findings suggest that
      ACTPK1 directly phosphorylates and inactivates AMT1;2 in rice seedling roots
      under sufficient ammonium.

PMID- 29356223
TI  - Sigma- versus Pi-Dimerization Modes of Triangulene.
AB  - We show that the diradicaloid triangulene, a graphene nano-flake molecule, can
      aggregate in a variety of dimerization modes. We found by density functional
      theory modeling a number of triangulene dimers including six doubly bonded sigma
      dimers in addition to the previously reported six pancake bonded pi-dimer
      isomers. The sigma-dimers display a wide range of stabilities: the interaction
      energy of the most stable sigma-dimer is -25.17 kcal mol-1 . Besides the doubly
      bonded sigma-dimers with closed shell ground states, we also found an open-shell
      singly sigma-bonded diradicaloid dimer. We found an interesting isomerization
      route between a doubly bonded sigma-dimer, a singly bonded sigma-dimer with a low
      lying triplet state and two pi-bonded dimers with low-lying quintet states.
      Derivatives of triangulene, trioxo-triangulenes (TOTs) have been previously
      characterized experimentally. Here, we show the reasons why so far only the pi
      dimer but not the sigma-dimer was experimentally observed for all TOTs.

PMID- 29356224
TI  - Sauchinone prevents IL-1beta-induced inflammatory response in human chondrocytes.
AB  - Sauchinone is one of the active lignan isolated from Saururus chinensis, which
      has been considered to possess various pharmacological activities, such as
      antitumor, hepatoprotective, antioxidant, and anti-inflammatory effects. However,
      the functional roles of sauchinone in interleukin-1 beta (IL-1beta)-stimulated
      human osteoarthritis (OA) chondrocytes are still unknown. Thus, in this study, we
      investigated the anti-inflammatory effects of sauchinone in IL-1beta-stimulated
      chondrocytes. Our results demonstrated that sauchinone significantly attenuated
      NO and PGE2 production, as well as inhibited iNOS and COX-2 expression in IL
      1beta-stimulated OA chondrocytes. In addition, sauchinone efficiently inhibited
      IL-1beta-induced MMP-3 and MMP-13 release in human OA chondrocytes. Furthermore,
      sauchinone significantly attenuated the activation of NF-kappaB in human OA
      chondrocytes. In conclusion, we showed for the first time that sauchinone
      inhibited inflammatory response in IL-1beta-stimulated human chondrocytes
      probably through inhibiting the activation of NF-kappaB signaling pathway. These
      data suggest that sauchinone may be a potential agent in the treatment of OA.

PMID- 29356225
TI  - Combining synthetic controls and interrupted time series analysis to improve
      causal inference in program evaluation.
AB  - RATIONALE, AIMS AND OBJECTIVES: Interrupted time series analysis (ITSA) is an
      evaluation methodology in which a single treatment unit's outcome is studied over
      time and the intervention is expected to "interrupt" the level and/or trend of
      the outcome. The internal validity is strengthened considerably when the treated
      unit is contrasted with a comparable control group. In this paper, we introduce a
      robust evaluation framework that combines the synthetic controls method (SYNTH)
      to generate a comparable control group and ITSA regression to assess covariate
      balance and estimate treatment effects. METHODS: We evaluate the effect of
      California's Proposition 99 for reducing cigarette sales, by comparing California
      to other states not exposed to smoking reduction initiatives. SYNTH is used to
      reweight nontreated units to make them comparable to the treated unit. These
      weights are then used in ITSA regression models to assess covariate balance and
      estimate treatment effects. RESULTS: Covariate balance was achieved for all but
      one covariate. While California experienced a significant decrease in the annual
      trend of cigarette sales after Proposition 99, there was no statistically
      significant treatment effect when compared to synthetic controls. CONCLUSIONS:
      The advantage of using this framework over regression alone is that it ensures
      that a comparable control group is generated. Additionally, it offers a common
      set of statistical measures familiar to investigators, the capability for
      assessing covariate balance, and enhancement of the evaluation with a
      comprehensive set of postestimation measures. Therefore, this robust framework
      should be considered as a primary approach for evaluating treatment effects in
      multiple group time series analysis.

PMID- 29356227
TI  - Efficacy of Peritoneal Dialysis in Neonates Presenting With Hyperammonaemia Due
      to Urea Cycle Defects and Organic Acidaemia.
AB  - AIM: Newborns with inborn errors of metabolism can present with hyperammonaemic
      coma. In this study, we evaluated the effect of peritoneal dialysis on plasma
      ammonium levels and on the short-term outcome in neonatal patients with urea
      cycle defects and organic acidaemia. METHODS: Data from infants with
      hyperammonaemia due to urea cycle defects or organic acidaemia treated with
      dialysis were collected and retrospectively analysed. The results of patient
      groups (group I, survived; and group II, died) were compared. RESULTS: Fourteen
      neonates were enrolled in this study. In group I, plasma ammonium levels before
      dialysis were median (IQR) 1652 MUg/dl (1165-2098 MUg/dl); in group II, they were
      1289 MUg/dl (1070-5550 MUg/dl). There was no statistically significant
      difference. Urea cycle defects were diagnosed in eight, and organic acidaemia in
      six patients. The duration of a blood ammonia level >200 MUg/dl was longer in
      group II (p=0.04). A <60.8 % decline in the ammonia level from the beginning of
      dialysis to the 12th hour of dialysis carried a 3.33-fold higher risk of
      mortality, when compared with a greater decline. Five patients with urea cycle
      defects, and one with organic acidaemia, died. The mortality risk was 8.33-fold
      (95% CI=0.63-90.86) higher for patients with urea cycle defects than for those
      with organic acidaemia. CONCLUSION: In patients with hyperammonaemia treated with
      peritoneal dialysis, the rate of ammonia removal and the underlying aetiology
      appear to be important prognostic factors. Neonates with organic acidaemia who
      are admitted to centres without continuous renal replacement therapy facilities
      can be effectively treated with peritoneal dialysis.

PMID- 29356226
TI  - 'I know I'm not invincible': An interpretative phenomenological analysis of
      thyroid cancer in young people.
AB  - OBJECTIVE: Thyroid cancer is one of the most common cancers affecting young
      people and carries an excellent prognosis. Little is known about the psychosocial
      issues that face young people diagnosed with a treatable cancer. This study
      explored how young people experienced diagnosis, treatment, and how they made
      sense of an experience which challenged their views on what it means to have
      cancer. METHOD: Semi-structured interviews were conducted with eight young people
      diagnosed with either papillary or follicular thyroid cancer, and analysed with
      interpretative phenomenological analysis (IPA). RESULTS: Two inter-related
      aspects of their experience are discussed: (1) the range of feelings and emotions
      experienced including feeling disregarded, vulnerability, shock and isolation;
      (2) how they made sense of and ascribed meaning to their experience in the light
      of the unique nature of their cancer. A thread running throughout the findings
      highlights that this was a disruptive biographical experience. CONCLUSIONS: Young
      people experienced a loss of youthful immunity which contrasted with a sense of
      growth and shift in life perspective. Having a highly treatable cancer was
      helpful in aiding them to reframe their situation positively but at the same time
      left them feeling dismissed over a lack of recognition that they had cancer. The
      young peoples' experiences point to a need for increased understanding of this
      rare cancer, more effective communication from health care professionals and a
      greater understanding of the experiential impact of this disease on young people.
      Suggestions to improve the service provision to this patient group are provided.
      Statement of contribution What is already known on this subject? Differentiated
      thyroid cancer has an excellent prognosis. Quality of life of thyroid cancer has
      marginally been explored in the literature. Little is known on the support needs
      of young people diagnosed with thyroid cancer. What does this study add?
      Increased understanding of how young people make sense and cope with thyroid
      cancer despite the lack of support resources. Addressing illness perceptions
      through improved information support may aid coping and adjustment. Insight into
      the needs of young people diagnosed with thyroid cancer and recommendations on
      service improvements.

PMID- 29356228
TI  - Curcuma sp.-derived dehydrocurdione induces heme oxygenase-1 through a Michael
      reaction between its alpha, beta-unsaturated carbonyl and Keap1.
AB  - To elucidate the anti-inflammatory mechanism of Curcuma sp., we investigated
      whether dehydrocurdione, a sesquiterpene contained in Curcuma sp., induces heme
      oxygenase (HO)-1, an antioxidative enzyme, in RAW 264.7 macrophages.
      Dehydrocurdione was extracted from the rhizome of Curcuma sp., and its purity was
      verified by high performance liquid chromatography. Treatment with 10-100 MUM
      dehydrocurdione transiently and concentration-dependently increased HO-1 mRNA and
      protein levels. Docking simulation suggested the presence of the Michael reaction
      between dehydrocurdione and Kelch-like ECH-associated protein (Keap)1 keeping
      nuclear factor-erythroid2-related-factor (Nrf)2, a transcription factor, in the
      cytoplasm. Nrf2 that was definitely free from Keap1 was detected in the nuclei
      after dehydrocurdione treatment. Subsequently, the HO-1 E2 enhancer, a target of
      Nrf2, was activated, resulting in HO-1 expression. Also, an investigation using 6
      shogaol and 6-gingerol supported the concept that the alpha, beta-unsaturated
      carbonyl structure plays an important role in the interaction with Keap1.
      Dehydrocurdione suppressed lipopolysaccharide-induced NO release, a marker of
      inflammation. Clarification of the HO-1 synthesis increase mechanism revealed in
      this study will help contribute to the development of novel phytotherapeutic
      strategies against inflammation-associated diseases.

PMID- 29356229
TI  - Brain tumor segmentation in multi-spectral MRI using convolutional neural
      networks (CNN).
AB  - A tumor could be found in any area of the brain and could be of any size, shape,
      and contrast. There may exist multiple tumors of different types in a human brain
      at the same time. Accurate tumor area segmentation is considered primary step for
      treatment of brain tumors. Deep Learning is a set of promising techniques that
      could provide better results as compared to nondeep learning techniques for
      segmenting timorous part inside a brain. This article presents a deep
      convolutional neural network (CNN) to segment brain tumors in MRIs. The proposed
      network uses BRATS segmentation challenge dataset which is composed of images
      obtained through four different modalities. Accordingly, we present an extended
      version of existing network to solve segmentation problem. The network
      architecture consists of multiple neural network layers connected in sequential
      order with the feeding of Convolutional feature maps at the peer level.
      Experimental results on BRATS 2015 benchmark data thus show the usability of the
      proposed approach and its superiority over the other approaches in this area of
      research.

PMID- 29356230
TI  - Maternal and child health nurses work with refugee families: Perspectives from
      regional Victoria, Australia.
AB  - AIMS AND OBJECTIVES: To explore service provision for Victorian regional refugee
      families from the perspective of maternal and child health nurses. BACKGROUND:
      Increasingly, more families from a refugee background are resettling in regional
      Victoria. The refugee journey has significant effect on families. Refugee
      families with infants and young children can be provided with support by maternal
      and child health services; however, many families experience barriers to ongoing
      engagement with this service. DESIGN: This descriptive study used focus group and
      questionnaire. A purposive sample of 26 maternal and child health nurses was
      drawn from six municipalities throughout regional Victoria, where higher numbers
      of people from a refugee background resettle. Six focus groups were held in 2014.
      Audio-recorded narratives were transcribed, prior to inductive thematic analysis.
      METHODS: This descriptive study used focus group and questionnaire. A purposive
      sample of 26 Maternal and Child Health nurses was drawn from six municipalities
      throughout regional Victoria where higher numbers of people from a refugee
      background resettle. Six focus groups were held in 2014. Audio-recorded
      narratives were transcribed verbatim, prior to inductive thematic analysis.
      RESULTS: Participating nurses were experienced nurses, averaging 12 years in the
      service. Four major themes emerged from thematic analysis: "How to identify women
      from a refugee background"; "The Maternal and Child Health nurse role when
      working with families from a refugee background"; "Interpreting issues"; and
      "Access to other referral agencies." Nurses worked to develop a relationship with
      families, attending to a complex mix of issues which were complicated by language
      barriers. Nurses found their role in supporting refugee families required
      additional time and more home visits. CONCLUSIONS: To provide best practice,
      maternal and child health nurses need (i) ongoing professional development; (ii)
      time, flexibility and creativity to build relationships with refugee families and
      (iii) better access to services that enhance communication, such as interpreting
      services and translated resources. RELEVANCE TO CLINICAL PRACTICE: Nurses require
      ongoing professional development to help them address the multifaceted needs of
      families of refugee background. With limited resources available in regional
      areas, accessing further education can be challenging. Distance education models
      and organisational support could provide nurses with educational opportunities
      aimed at improving service provision and clinical practice.

PMID- 29356231
TI  - A case of erectile dysfunction induced by red yeast rice in lipid-lowering
      therapy.
AB  - This paper studies a 39-year-old male patient who takes red yeast rice (RYR) for
      self-therapy in lipid-lowering for 3 weeks. Results show that RYR can decrease
      most of the blood lipid components but without selectivity. During the treatment,
      the patient developed erectile dysfunction (ED) and accompanied by a dramatic
      decrease in sexual desire. The ED symptom gradually disappeared within 5 weeks
      after stopping RYR intake.

PMID- 29356232
TI  - A Modular Nanoswitch for Mix-and-Detect Protein Assay Based on Binding-Induced
      Cascade Dissociation of Kissing Complex.
AB  - A new modular nanoswitch was described for versatile, rapid (within 1 h),
      homogeneous, and sensitive protein detection. The system employs two hairpins
      (HP1 and HP2) that can be reciprocally recognized through the apical loop-loop
      interaction. HP2 possesses a conformation-switching stem-loop structure, with
      appended single-stranded tails on each end, which can hybridize with the
      recognition-element-conjugated DNA strands to construct a protein-responsive HP2
      scaffold. It works according to a simple mix-and-detect assay format, with the
      first formation of a kissing complex between HP1 and HP2 scaffolds for
      fluorescence quenching, and then cascade propagation from steric strain through
      protein binding to the dissociation of the kissing complex for fluorescence
      recovery. The detection universality of such a modular nanoswitch was
      demonstrated by using three multivalent proteins, including anti-digoxigenin
      (Anti-Dig) antibody, streptavidin, and thrombin, with detection limits of 0.33,
      0.17, and 0.5 nm, respectively.

PMID- 29356233
TI  - A Three-Component Organometallic Tyrosine Bioconjugation.
AB  - Metal-based bioconjugation linkages represent a little-studied approach to
      protein functionalization that provides novel reactivity, stability, and
      function. Described is an organometallic bioconjugation, employing rhodium(III)
      salts, to link boronic acids with tyrosine residues by an arene complex. Both
      peptides and proteins are amenable to the mild bioconjugation in aqueous media,
      allowing incorporation of useful functionalities, such as affinity handles or
      fluorophores. Because of the metastability of the inorganic linkage, the
      conjugates are susceptible to cleavage by nucleophilic redox mediators but are
      stable toward typical biological conditions.

PMID- 29356234
TI  - Recent Development of Thermoelectric Polymers and Composites.
AB  - Thermoelectric materials can be used as the active materials in thermoelectric
      generators and as Peltier coolers for direct energy conversion between heat and
      electricity. Apart from inorganic thermoelectric materials, thermoelectric
      polymers have been receiving great attention due to their unique advantages
      including low cost, high mechanical flexibility, light weight, low or no
      toxicity, and intrinsically low thermal conductivity. The power factor of
      thermoelectric polymers has been continuously rising, and the highest ZT value is
      more than 0.25 at room temperature. The power factor can be further improved by
      forming composites with nanomaterials. This article provides a review of recent
      developments on thermoelectric polymers and polymer composites. It focuses on the
      relationship between thermoelectric properties and the materials structure,
      including chemical structure, microstructure, dopants, and doping levels. Their
      thermoelectric properties can be further improved to be comparable to inorganic
      counterparts in the near future.

PMID- 29356235
TI  - Contribution of intraoperative radiotherapy (IORT) for therapeutic de-escalation
      in early breast cancer: Report of a single institution's experience.
AB  - The spread of systematic screening and the emergence of oncoplastic techniques
      allow more breast conservative treatment associating lumpectomy and external beam
      radiation therapy. In order to furthermore facilitate the patient's treatment,
      intraoperative radiation therapy (IORT) has been developed. The oncological
      safety of this technique has been studied, and is considered acceptable. Many
      questions remain unsolved in regard of the toxicity of this procedure as well as
      the patient's selection criteria. In this study, we present the first results and
      complications rate of patients treated by IORT in a single French institution.
      Between 2012 and 2015, all patients with breast cancer treated in a one-step
      procedure associating lumpectomy and IORT were retrospectively included in a
      monocentric cohort. Acute and long-term toxicities were evaluated using CTCAE
      v4.0 classification. 280 breast cancers were treated using IORT procedure.
      Additional external beam radiation therapy was requested for 45.7% patients. The
      acute complications rate was 14.6%, with 5 surgical revisions needed (1.78%).
      With a median follow up of 911 days, the long-term grade-3 toxicity rate was
      1.1%. The only risk factor for local fibrosis was external beam radiation therapy
      (EBRT) (OR = 1.99; IC95 [1.05-3.81], P = 0.036). Three patients (1.07%) were
      diagnosed with local recurrence. The results from this cohort confirm the low
      complication and recurrence rate of IORT procedure. A good selection of patients
      is necessary in order to lower the EBRT rate and allow therapeutic de-escalation.
      The classification of tumors into IHC subsets seems a good selection gate.
      Intraoperative radiation therapy appears to have a low toxicity rate with an
      acceptable local recurrence risk, and should therefore be considered as an option
      in the treatment of early breast cancer.

PMID- 29356237
TI  - AF news.

PMID- 29356236
TI  - Isolation and characterization of heterotrophic nitrifying and aerobic
      denitrifying Klebsiella pneumoniae and Klebsiella variicola strains from various
      environments.
AB  - AIMS: We sought to isolate novel heterotrophic nitrifying and aerobic
      denitrifying Klebsiella pneumoniae and Klebsiella variicola strains from various
      natural environments and characterize their nitrogen removal processes. METHODS
      AND RESULTS: Ten novel Klebsiella strains with heterotrophic nitrification and
      aerobic denitrification abilities, including seven K. pneumoniae and three K.
      variicola, were successfully isolated from faeces, sewage, plant surfaces and
      sludge. A 1674-bp fragment of the hydroxylamine oxidase (hao) gene was
      successfully amplified from the novel strains. The removal rates of ammonium,
      nitrate and nitrite of the seven K. pneumoniae isolates were 96.42-97.38%, 61.27
      82.78% and 100%, respectively, and the corresponding degradation ratios were 4.82
      6.49 (higher than previously reported for K. pneumoniae CF-S9 and EGD-HP19-C),
      1.15-1.38 and 1.48-3.33 mg l-1  h-1 , respectively. The removal rates of
      ammonium, nitrate and nitrite of the three K. variicola isolates were 95.01
      96.15%,68.60--78.37% and 100%, respectively, and the corresponding degradation
      ratios were 4.79-9.5, 1.14-1.74 and 1.67-4.44 mg l-1  h-1 , respectively. The K.
      variicola strain sd-3 from sludge exhibited the best heterotrophic nitrification
      and aerobic denitrification abilities among the isolates. Meanwhile, the results
      of simultaneous nitrification and denitrification assays with all isolated
      strains showed that ammonium was removed prior to nitrate or nitrite.
      CONCLUSIONS: Our results indicate that K. pneumoniae and K. variicola (isolated
      from a novel natural environment) play an important role in the Earth's nitrogen
      cycle in various natural environments. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study is one of only a few works to successfully isolate K. pneumoniae with
      heterotrophic nitrification and aerobic denitrification abilities in various
      natural environments. The physiological characterization K. variicola as having
      abilities to heterotrophically nitrify and aerobically denitrify is the first to
      be reported. Moreover, this study may provide alternative microbial resources for
      the removal of nitrogen from wastewater.

PMID- 29356238
TI  - GC/MS analysis and characterization of 2-Hexadecen-1-ol and beta sitosterol from
      Schimpera arabica extract for its bioactive potential as antioxidant and
      antimicrobial.
AB  - AIMS: We evaluated the in vitro antioxidant and antimicrobial potential of
      Schimpera arabica extract and fractions (2-Hexadecen-1-ol and beta sitosterol).
      METHODS AND RESULTS: Free radical scavenging activity was estimated by using ABTS
      and DPPH methods, reducing power and iron chelation was studied to investigate
      antioxidant potential of the extracts. Well-diffusion method was utilized to
      evaluate the antimicrobial activity of the extracts. Gas chromatography-mass
      spectroscopy analysis of the extract revealed the presence of 27 compounds.
      Phenolic and flavonoid contents were found in high amount (7.6-18 mg GAE, mg g-1
      ; 3.2-10.8 mg catechin, mg g-1 ) in dry plant material. CONCLUSIONS: Among all
      the extracts, 2-Hexadecen-1-ol and beta sitosterol were the major constituents of
      crude extract and exhibited significant antioxidant potential as well
      antimicrobial activity; however, all other fractions also exhibited fare degree
      of antioxidant potential. 93% DPPH was scavenged by 100 MUg ml-1 of the ethyl
      acetate fraction; in ABTS assay chelation was 86.2 and 88% in ferric chloride
      reducing power assay. SIGNIFICANCE AND IMPACT OF THE STUDY: Schimpera arabica is
      naturally present and used in food preparation in most Arabian nations. The
      characterization of S. arabica would provide an insight into its medicinal use as
      home remedial for bacterial infection and as antioxidant. Significant and
      comparable antimicrobial activity was demonstrated by both 2-Hexadecen-1-ol and
      beta sitosterol fractions. The results suggest that S. arabica contain a good
      amount of natural antioxidants of medicinal importance. However, further
      investigations are needed to characterize the further activity of 2-Hexadecen-1
      ol and beta sitosterol in vivo.

PMID- 29356239
TI  - Phonological processing during silent reading in teenagers who are deaf/hard of
      hearing: an eye movement investigation.
AB  - There has been considerable variability within the literature concerning the
      extent to which deaf/hard of hearing individuals are able to process phonological
      codes during reading. Two experiments are reported in which participants' eye
      movements were recorded as they read sentences containing correctly spelled words
      (e.g., church), pseudohomophones (e.g., cherch), and spelling controls (e.g.,
      charch). We examined both foveal processing and parafoveal pre-processing of
      phonology for three participant groups-teenagers with permanent childhood hearing
      loss (PCHL), chronological age-matched controls, and reading age-matched
      controls. The teenagers with PCHL showed a pseudohomophone advantage from both
      directly fixated words and parafoveal preview, similar to their hearing peers.
      These data provide strong evidence for phonological recoding during silent
      reading in teenagers with PCHL.

PMID- 29356240
TI  - Seroprevalence of leptospiral antibodies among market workers and food handlers
      in the central state of Malaysia.
AB  - OBJECTIVE: The high prevalence of leptospirosis in humans is of great public
      health concern, particularly in tropical and subtropical regions. This study
      aimed to determine the seroprevalence of leptospiral antibodies and distribution
      of serovars, and to assess the usefulness of enzyme-linked immunosorbent assay
      (ELISA) as a screening method for leptospiral antibodies in a high-risk healthy
      community. METHODS: Cross-sectional study of 231 market workers and food handlers
      in wet markets and food premises from two localities in central Malaysia.
      Respondents' background information was obtained using a questionnaire. Serum
      samples were tested for leptospiral antibodies using ELISA and microscopic
      agglutination test (MAT). RESULTS: Seroprevalence of leptospirosis among healthy
      workers was 46.3%. Detection of seropositivity was higher by MAT (46%) than ELISA
      (15%). We observed high seropositivity among local workers (49%), food handlers
      (49.5%), females (60.8%) and those aged 34 years and older (46.3%). Local strain
      LEP175 was the predominant serovar, followed by WHO strain Patoc. CONCLUSION:
      Overall seroprevalence among healthy food handlers and market workers was high in
      this study. The workplace places susceptible individuals at risk of
      leptospirosis.

PMID- 29356241
TI  - Tumor necrosis factor-alpha regulates human follicular dendritic cell-secreted
      protein gene transcription in gingival epithelial cells.
AB  - Follicular dendritic cell-secreted protein (FDC-SP) is a secreted protein
      expressed in follicular dendritic cells, periodontal ligament and junctional
      epithelium. To elucidate the transcriptional regulation of the human FDC-SP gene
      by tumor necrosis factor-alpha (TNF-alpha), we conducted real-time PCR, Western
      blotting, transient transfection analyses with chimeric constructs of the FDC-SP
      gene promoter linked to a luciferase reporter gene, gel mobility shift and
      chromatin immunoprecipitation assays using Ca9-22 gingival epithelial cells. TNF
      alpha (10 ng/ml) induced FDC-SP mRNA and protein levels at 3 hr and reached
      maximum at 12 hr. In transient transfection assays, TNF-alpha (12 hr) increased
      the LUC activities of constructs between -116FDCSP and -948FDCSP including the
      human FDC-SP gene promoter. Transcriptional stimulations by TNF-alpha were
      partially inhibited in the -345FDCSP constructs that included 3-bp mutations in
      the YY1, GATA, CCAAT enhancer-binding protein 2 (C/EBP2) and C/EBP3.
      Transcriptional activities induced by TNF-alpha were inhibited by tyrosine
      kinase, MEK1/2 and phosphoinositide 3-kinase inhibitors. The results of ChIP
      assays showed that YY1, GATA and C/EBPbeta transcription factors interacted with
      the YY1, GATA, C/EBP2 and C/EBP3 elements that were increased by TNF-alpha. These
      studies show that TNF-alpha stimulates human FDC-SP gene transcription by
      targeting YY1, GATA, C/EBP2 and C/EBP3 in the FDC-SP gene promoter.

PMID- 29356242
TI  - Preferable in vitro condition for maintaining faithful DNA methylation imprinting
      in mouse embryonic stem cells.
AB  - Epigenetic properties of cultured embryonic stem cells (ESCs), including DNA
      methylation imprinting, are important because they affect the developmental
      potential. Here, we tested a variety of culture media, including knockout serum
      replacement (KSR) and fetal bovine serum (FBS) with or without inhibitors of
      Gsk3beta and Mek1/2 (2i) at various time points. In addition to the previously
      known passage-dependent global changes, unexpected dynamic DNA methylation
      changes occurred in both maternal and paternal differentially methylated regions:
      under the widely used condition of KSR with 2i, a highly hypomethylated state
      occurred at early passages (P1-7) as well as P10, but DNA methylation increased
      over further passages in most conditions, except under KSR with 2i at P25.
      Dramatic DNA demethylation under KSR+2i until P25 was associated with upregulated
      Tet1 and Parp1, and their related genes, whereas 2i regulated the expressions of
      DNA methyltransferase-related genes for the change in DNA methylation during the
      cumulative number of passages. Although DNA methylation imprinting is more labile
      under KSR with and without 2i, it can be more faithfully maintained under
      condition of cooperative FBS and 2i. Thus, our study will provide the useful
      information for improved epigenetic control of ESCs and iPSCs in applications in
      regenerative medicine.

PMID- 29356243
TI  - Major limitations to achieving "4 per 1000" increases in soil organic carbon
      stock in temperate regions: Evidence from long-term experiments at Rothamsted
      Research, United Kingdom.
AB  - We evaluated the "4 per 1000" initiative for increasing soil organic carbon (SOC)
      by analysing rates of SOC increase in treatments in 16 long-term experiments in
      southeast United Kingdom. The initiative sets a goal for SOC stock to increase by
      40/00 per year in the 0-40 cm soil depth, continued over 20 years. Our
      experiments, on three soil types, provided 114 treatment comparisons over 7-157
      years. Treatments included organic additions (incorporated by inversion
      ploughing), N fertilizers, introducing pasture leys into continuous arable
      systems, and converting arable land to woodland. In 65% of cases, SOC increases
      occurred at >70/00 per year in the 0-23 cm depth, approximately equivalent to
      40/00 per year in the 0-40 cm depth. In the two longest running experiments (>150
      years), annual farmyard manure (FYM) applications at 35 t fresh material per
      hectare (equivalent to approx. 3.2 t organic C/ha/year) gave SOC increases of
      180/00 and 430/00 per year in the 23 cm depth during the first 20 years.
      Increases exceeding 70/00 per year continued for 40-60 years. In other
      experiments, with FYM applied at lower rates or not every year, there were
      increases of 30/00-80/00 per year over several decades. Other treatments gave
      increases between zero and 190/00 per year over various periods. We conclude that
      there are severe limitations to achieving the "4 per 1000" goal in practical
      agriculture over large areas. The reasons include (1) farmers not having the
      necessary resources (e.g. insufficient manure); (2) some, though not all,
      practices favouring SOC already widely adopted; (3) practices uneconomic for
      farmers-potentially overcome by changes in regulations or subsidies; (4)
      practices undesirable for global food security. We suggest it is more realistic
      to promote practices for increasing SOC based on improving soil quality and
      functioning as small increases can have disproportionately large beneficial
      impacts, though not necessarily translating into increased crop yield.

PMID- 29356244
TI  - Rapid and Efficient Generation of Stable Antibody-Drug Conjugates via an Encoded
      Cyclopropene and an Inverse-Electron-Demand Diels-Alder Reaction.
AB  - Homogeneous antibody-drug conjugates (ADCs), generated by site-specific toxin
      linkage, show improved therapeutic indices with respect to traditional ADCs.
      However, current methods to produce site-specific conjugates suffer from low
      protein expression, slow reaction kinetics, and low yields, or are limited to
      particular conjugation sites. Here we describe high yielding expression systems
      that efficiently incorporate a cyclopropene derivative of lysine (CypK) into
      antibodies through genetic-code expansion. We express trastuzumab bearing CypK
      and conjugate tetrazine derivatives to the antibody. We show that the
      dihydropyridazine linkage resulting from the conjugation reaction is stable in
      serum, and generate an ADC bearing monomethyl auristatin E that selectively kills
      cells expressing a high level of HER2. Our results demonstrate that CypK is a
      minimal bioorthogonal handle for the rapid production of stable therapeutic
      protein conjugates.

PMID- 29356245
TI  - Predicting survival of older community-dwelling individuals according to five
      estimated glomerular filtration rate equations: The InChianti study.
AB  - AIMS: There is uncertainty about which estimated glomerular filtration rate eGFR
      equation to use in older people with respect to the prediction of prognosis. Our
      aim was: (i) to compare the discriminative capacity of eGFR estimated by
      different equations with respect to all-cause mortality; and (ii) to identify the
      eGFR threshold at which the risk of mortality starts to increase for each
      equation. METHODS: We used data from 828 community-dwelling older adults aged >65
      years enrolled in the InCHIANTI study. The outcome measure was all-cause
      mortality at 9 years. GFR was estimated by five different equations: Chronic
      Kidney Disease Epidemiological Collaboration (creatinine equation [CKD-EPIcre ],
      and creatinine and cystatin C equation [CKD-EPIcre-cys ]), Berlin Initiative
      Study (BIScre and BIScre-cys ) and full age spectrum. Sensitivity, specificity,
      areas under receiver operating curve (AUC) and C-statistics were used to compare
      their predictive capacity. RESULTS: The best mix of sensitivity, specificity, AUC
      and C-statistic value in predicting mortality was observed with BIS equations.
      BIScre (AUC 0.65, 95% CI 0.61-0.69) outperformed both CKD-EPIcre (AUC 0.60, 95%
      CI 0.56-0.64; P = 0.005) and full age spectrum (AUC 0.63, 95% CI 0.59-0.67; P =
      0.002) in terms of predictivity. Similarly, BIScre-cys (AUC 0.67, 95% CI 0.63
      0.71) outperformed CKD-EPIcre-cys (AUC 0.63, 95% CI 0.59-0.67; P = 0.01). AUC
      obtained with equations also including cystatin C were not significantly
      different compared with their creatinine-based counterparts. The risk of long
      term mortality began to increase at under 65.6 mL/min/1.73 m2 for CKD-EPIcre-cys
      , 60.5 for CKD-EPIcre , 60 for BIScre-cys , 56.3 for BIScre and 55.2 for full age
      spectrum. CONCLUSIONS: The BIS equation discriminates the risk of all-cause
      mortality better than other equations in older community-dwelling individuals.
      The eGFR threshold under which mortality starts to increase could change as a
      function of the equation used. Geriatr Gerontol Int 2018; 18: 607-614.

PMID- 29356246
TI  - Amipurimycin: Total Synthesis of the Proposed Structures and Diastereoisomers.
AB  - The proposed diastereoisomers (1 a-d) together with their C8'-epimers (1 e-h) of
      amipurimycin, a unique antifungal peptidyl nucleoside antibiotic, have been
      synthesized for the first time. The synthetic approach is efficient and
      stereodivergent, and features a stereoselective aldol condensation to build the
      branched C9 sugar amino acid skeleton and a regio- and stereocontrolled gold(I)
      catalyzed N-glycosylation to furnish the purine nucleoside. Analysis of the NMR
      data suggests that the previously assigned configuration of the tertiary C3' in
      amipurimycin should be of opposite configuration.

PMID- 29356247
TI  - A comprehensive survey of Aeromonas sp. and Vibrio sp. in seabirds from
      southeastern Brazil: outcomes for public health.
AB  - AIMS: To perform a microbiological survey regarding the presence, prevalence and
      characterization of Aeromonas sp. and Vibrio sp. in debilitated wrecked marine
      birds recovered from the centre-north coast of the state of Rio de Janeiro,
      Brazil. METHODS AND RESULTS: Swabs obtained from 116 alive and debilitated
      wrecked marine birds, comprising 19 species, from the study area were evaluated
      by biochemical methods. Antimicrobial susceptibility tests and pathogenicity gene
      screening were performed for bacterial strains of public health importance.
      Vibrio sp. and Aeromonas sp. were identified, as well as certain pathogenic genes
      and resistance to selected antimicrobials. CONCLUSIONS: This study demonstrates
      that the identified bacteria, mainly Vibrio sp., are fairly prevalent and
      widespread among several species of seabirds and highlights the importance of
      migratory birds in bacterial dispersion. In addition, it demonstrates the
      importance of the bacterial strains regarding their pathogenic potential.
      Therefore, seabirds can act as bacterial reservoirs, and their monitoring is of
      the utmost importance in a public health context. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study comprehensively evaluates the importance of seabirds as bacteria
      of public health importance reservoirs, since birds comprising several pathogenic
      bacterial species were evaluated.

PMID- 29356248
TI  - Effect on transcriptome and metabolome of stacked transgenic maize containing
      insecticidal cry and glyphosate tolerance epsps genes.
AB  - Gene stacking is a developing trend in agricultural biotechnology. Unintended
      effects in stacked transgenic plants are safety issues considered by the public
      and researchers. Omics techniques provide useful tools to assess unintended
      effects. In this paper, stacked transgenic maize 12-5*IE034 that contained
      insecticidal cry and glyphosate tolerance G10-epsps genes was obtained by
      crossing of transgenic maize varieties 12-5 and IE034. Transcriptome and
      metabolome analyses were performed for different maize varieties, including 12
      5*IE034, 12-5, IE034, and conventional varieties collected from different
      provinces in China. The transcriptome results were as follows. The nine maize
      varieties had obvious differences in gene expression. There were 3561-5538
      differentially expressed genes between 12-5*IE034 and its parents and transgenic
      receptor, which were far fewer than the number of differentially expressed genes
      in different traditional maize varieties. Cluster analysis indicated that there
      were close relationships between 12-5*IE034 and its parents. The metabolome
      results were as follows. For the nine detected maize varieties, the number of
      different metabolites ranged from 0 to 240. Compared with its parents, 12-5 and
      IE034, the hybrid variety 12-5*IE034 had 15 and 112 different metabolites,
      respectively. Hierarchical cluster analysis with Pearson's correlation analysis
      showed that the differences between 12-5*IE034 and its parents were fewer than
      those between other maize varieties. Shikimate pathway-related genes and
      metabolites analysis results showed that the effects of hybrid stacking are less
      than those from transformation and differing genotypes. Thus, the differences due
      to breeding stack were fewer than those due to natural variation among maize
      varieties. This paper provides scientific data for assessing unintended effects
      in stacked transgenic plants.

PMID- 29356249
TI  - Effect of Origanum vulgare essential oil on biofilm formation and motility
      capacity of Pseudomonas fluorescens strains isolated from discoloured Mozzarella
      cheese.
AB  - AIMS: The study was focused on Pseudomonas fluorescens strains isolated from
      Mozzarella cheese, with the aim of evaluating the effects of Origanum vulgare L.
      essential oil (OEO) on the biofilm formation and eradication, as well as on the
      motility and blue pigment production at 10 degrees C. METHODS AND RESULTS:
      Microdilution method was used to determine the minimum inhibitory and
      bactericidal concentration of the OEO, which ranged between 10 and 40 MUl ml-1 .
      In vitro studies demonstrated that a sublethal concentration of OEO influenced
      not only P. fluorescens growth and motility but also the capability to form
      biofilm and, in a lower degree, the biofilm eradication at 10 degrees C. Analysis
      by confocal microscopy revealed a dramatic reduction in biofilm formation and
      thickness, with scattered damage or death of cells, stained by propidium iodide.
      In addition, a concentration of 5 MUl ml-1 of OEO affected the motility of the
      cells and, in particular, their ability to swim. However, the essential oil did
      not inhibit the blue pigment production by any of the tested strains.
      CONCLUSIONS: The present findings suggest that oregano essential oil inhibits the
      biofilm formation of P. fluorescens strains and alters their motility. Moreover,
      in the preformed biofilm, OEO contributes to the detachment of the cells,
      deteriorating the architecture of the biofilm and reducing its thickness.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The O. vulgare L. essential oil was
      revealed as a promising agent against biofilm formation and for its detaching;
      these results suggest that oregano EO could be used in the dairy food industry to
      control biofilm formation, as an alternative, or in combination with conventional
      sanitizers.

PMID- 29356250
TI  - Application of the Interacting Quantum Atoms Approach to the S66 and Ionic
      Hydrogen-Bond Datasets for Noncovalent Interactions.
AB  - The interacting quantum atoms (IQA) method can assess, systematically and in
      great detail, the strength and physics of both covalent and noncovalent
      interactions. The lack of a pair density in density functional theory (DFT),
      which precludes the direct IQA decomposition of the characteristic exchange
      correlation energy, has been recently overcome by means of a scaling technique,
      which can largely expand the applicability of the method. To better assess the
      utility of the augmented IQA methodology to derive quantum chemical
      decompositions at the atomic and molecular levels, we report the results of
      Hartree-Fock (HF) and DFT calculations on the complexes included in the S66 and
      the ionic H-bond databases of benchmark geometry and binding energies. For all
      structures, we perform single-point and geometry optimizations using HF and
      selected DFT methods with triple-zeta basis sets followed by full IQA
      calculations. Pairwise dispersion energies are accounted for by the D3 method. We
      analyze the goodness of the HF-D3 and DFT-D3 binding energies, the magnitude of
      numerical errors, the fragment and atomic distribution of formation energies,
      etc. It is shown that fragment-based IQA decomposes the formation energies in
      comparable terms to those of perturbative approaches and that the atomic IQA
      energies hold the promise of rigorously quantifying atomic and group energy
      contributions in larger biomolecular systems.

PMID- 29356251
TI  - Dedifferentiated Fat (DFAT) cells: A cell source for oral and maxillofacial
      tissue engineering.
AB  - Tissue engineering is a promising method for the regeneration of oral and
      maxillofacial tissues. Proper selection of a cell source is important for the
      desired application. This review describes the discovery and usefulness of
      dedifferentiated fat (DFAT) cells as a cell source for tissue engineering.
      Dedifferentiated Fat cells are a highly homogeneous cell population (high
      purity), highly proliferative, and possess a multilineage potential for
      differentiation into various cell types under proper in vitro inducing conditions
      and in vivo. Moreover, DFAT cells have a higher differentiation capability of
      becoming osteoblasts, chondrocytes, and adipocytes than do bone marrow-derived
      mesenchymal stem cells and/or adipose tissue-derived stem cells. The usefulness
      of DFAT cells in vivo for periodontal tissue, bone, peripheral nerve, muscle,
      cartilage, and fat tissue regeneration was reported. Dedifferentiated Fat cells
      obtained from the human buccal fat pad (BFP) are a minimally invasive procedure
      with limited esthetic complications for patients. The BFP is a convenient and
      accessible anatomical site to harvest DFAT cells for dentists and oral surgeons,
      and thus is a promising cell source for oral and maxillofacial tissue
      engineering.

PMID- 29356252
TI  - White Matter Integrity Disruptions Correlate With Cognitive Impairments in
      Asthma.
AB  - BACKGROUND: Cognitive impairments are common in asthma, which is a serious global
      health problem characterized by chronic airway inflammation. However, the
      underlying neuromechanism is still unclear. PURPOSE/HYPOTHESIS: To investigate
      the neuromechanism underlying cognitive impairments of asthma. We hypothesized
      that asthma patients exhibit altered white matter (WM) microstructures, which may
      contribute to their cognitive impairments. STUDY TYPE: Case-control study.
      SUBJECTS: 37 patients with asthma (14 male) and 31 healthy controls (10 male).
      FIELD STRENGTH/SEQUENCE: Diffusion tensor imaging (DTI) covering the whole brain
      was acquired on a 3.0T scanner using a single-shot echo planar imaging sequence.
      ASSESSMENT: A DTI with tract-based spatial statistics (TBSS) approach was used to
      investigate the whole-brain differences in the WM fractional anisotropy (FA)
      values. STATISTICAL TESTS: Demographic and neuropsychological data were performed
      using two independent sample t-test or chi-square test or Mann-Whitney rank test.
      The relationship between cognitive impairments and WM abnormalities was studied
      using correlation analyses. RESULTS: Impairments of language ability, executive
      function, and visual-spatial processing and widespread WM disruptions reflected
      by FA reduction were found in asthma patients. The executive function was related
      to left forceps major, cingulum, and right uncinate fasciculus, ILF (inferior
      longitudinal fasciculus) positively (P < 0.05). FA abnormalities were positively
      correlated with duration of asthma and asthma control test (ACT) scores. DATA
      CONCLUSION: Asthma patients display multiple cognitive impairments and
      universally WM integrity disruptions, among which executive dysfunction closely
      correlates with WM abnormalities. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage
      5 J. Magn. Reson. Imaging 2018.

PMID- 29356253
TI  - Current protein and amino acid intakes among Japanese people: Analysis of the
      2012 National Health and Nutrition Survey.
AB  - AIM: To evaluate protein and amino acid intakes and distribution among Japanese
      people in terms of prevention of sarcopenia or frailty. METHODS: We carried out a
      cross-sectional study using data from Japan's 2012 National Health and Nutrition
      Survey. From the original dataset, we selected individuals aged >=30 years, who
      were not pregnant or lactating, and for whom dietary intake, bodyweight and body
      height data were available. Protein intake was calculated using exclusive
      software developed for the survey. Amino acid intake was calculated using the
      database created by the National Institute for Longevity Sciences. RESULTS: More
      than 95% of the participants met recommended levels of protein suggested by the
      Dietary Reference Intake in Japan. However, nearly half of the participants did
      not meet recommended levels in terms of prevention of sarcopenia. Leucine intake
      was not sufficient for each sex and age group, probably because of decreased
      intake of animal protein, especially protein from milk and dairy products.
      Distribution of protein and leucine in each meal tended toward dinner.
      CONCLUSIONS: The Japanese population might have insufficient quality, quantity
      and distribution of protein intake required to prevent sarcopenia or frailty.
      Geriatr Gerontol Int 2018; 18: 723-731.

PMID- 29356254
TI  - Effects of school-based mindfulness training on emotion processing and well-being
      in adolescents: evidence from event-related potentials.
AB  - In a non-randomized controlled study, we investigated the efficacy of a school
      based mindfulness curriculum delivered by schoolteachers to older secondary
      school students (16-18 years). We measured changes in emotion processing indexed
      by P3b event-related potential (ERP) modulations in an affective oddball task
      using static human faces. ERPs were recorded to happy and sad face oddballs
      presented in a stimulus stream of frequent faces with neutral expression, before
      and after 8 weeks of mindfulness training. Whilst the mean amplitude of the P3b,
      an ERP component typically elicited by infrequent oddballs, decreased between
      testing sessions in the control group, it remained unchanged in the training
      group. Significant increases in self-reported well-being and fewer doctor visits
      for mental health support were also reported in the training group as compared to
      controls. The observed habituation to emotional stimuli in controls thus
      contrasted with maintained sensitivity in mindfulness-trained students. These
      results suggest that in-school mindfulness training for adolescents has scope for
      increasing awareness of socially relevant emotional stimuli, irrespective of
      valence, and thus may decrease vulnerability to depression.

PMID- 29356255
TI  - Development of an online, universal, Utstein registry-based, care practice report
      card to improve out-of-hospital resuscitation practices.
AB  - RATIONALE, AIMS AND OBJECTIVES: Care quality is a primary concern in health
      field. In France, the care practice report card (CPRC) is compulsory for
      practitioners. It is the first step towards the culture of excellence. In this
      context, practitioners have to assess and improve their practices. Competent
      authorities define registries as reliable sources for CPRC. The first aim of this
      work is to describe how we designed and built a universally transposable CPRC
      model based on an Utstein-style cardiac arrest registry. The second aim is to
      measure the adherence of practitioners to this approach and to show how such a
      tool can be used in real situation. METHODS: Our report card is adapted from in
      hospital CA care quality and safety indicators. We built a 2-section grid. The
      first part described the quality and completeness of the analysed data. The
      second part distinguished medical and traumatic CA and assesses care practices.
      We analysed the practitioners' adherence thanks to a satisfaction survey.
      Finally, we presented a CPRC case study. RESULTS: This tool was tested in 92
      centres gathering 8433 patients. The satisfaction survey showed that this CPRC
      was well accepted by emergency professionals. We presented an implementation
      example of this tool in a centre in real-life situation. CONCLUSIONS: We designed
      and implemented a fully automated CPRC tool routinely usable for Utstein-style CA
      registries. This CPRC is easily transferable in all other Utstein CA registries.
      The debriefing report source codes are freely distributed upon request. This tool
      enables the care assessment and improvement.

PMID- 29356258
TI  - Congenital myasthenic syndrome due to DPAGT1 mutations mimicking congenital
      myopathy in an Irish family.

PMID- 29356256
TI  - Investigation of Microalgal Carotenoid Content Using Coherent Anti-Stokes Raman
      Scattering (CARS) Microscopy and Spontaneous Raman Spectroscopy.
AB  - The yield of high-value products, such as pigments that could be extracted from
      microalgae, is affected by various nutritional and physical factors.
      Consequently, there is a need for fast visualization techniques that investigate
      the responses of individual microalgal cells to changing environmental conditions
      without introducing perturbations. Here, we apply CARS microscopy to map the
      distribution of pigments in the diatoms Ditylum brightwellii and Stephanopyxis
      turris and report their relative change in response to varying light cycles using
      a marker-based watershed analysis of the acquired images. Simultaneously, the
      underlying specific pigment composition alterations are revealed using Raman
      microspectroscopy at 785 nm excitation. In regards to assessing the chemical
      content of microalgae, these methods present themselves as viable alternatives to
      the standard techniques currently in use because of their non-disruptive nature
      and the wealth of complementary information that could be obtained from them.

PMID- 29356259
TI  - Miller Fisher syndrome associated with a Zika virus infection.

PMID- 29356260
TI  - 18 F-NaF PET-MRI: an innovative tool to assess carotid artery plaque
      vulnerability.

PMID- 29356261
TI  - CLIPPERS mimickers: relapsing brainstem encephalitis associated with anti-MOG
      antibodies.

PMID- 29356262
TI  - Optic nerve sheath diameter measurement in patients with idiopathic normal
      pressure hydrocephalus.

PMID- 29356263
TI  - Pyridostigmine bromide versus fludrocortisone in the treatment of orthostatic
      hypotension in Parkinson's disease - reply.

PMID- 29356264
TI  - Corpus callosum agenesis, myopathy and pinpoint pupils: consider Stormorken
      syndrome.

PMID- 29356265
TI  - Palladium-Catalyzed Oxygenative Cross-Coupling of Ynamides and Benzyl Bromides by
      Carbene Migratory Insertion.
AB  - A palladium-catalyzed oxygenative cross-coupling of ynamides and benzyl bromides
      has been developed. After subsequent hydrogenation, alpha,alpha-disubstituted
      amide derivatives were obtained in good yields. Migratory insertion of alpha-oxo
      palladium carbene species, generated by intermolecular oxidation, is proposed as
      the key step in this reaction. The study demonstrates the potential of ynamides
      to serve as carbene precursors in palladium-catalyzed C-C bond-forming cross
      coupling reactions.

PMID- 29356266
TI  - On the Action of General Anesthetics on Cellular Function: Barbiturate Alters the
      Exocytosis of Catecholamines in a Model Cell System.
AB  - General anesthetics are essential in many areas, however, the cellular mechanisms
      of anesthetic-induced amnesia and unconsciousness are incompletely understood.
      Exocytosis is the main mechanism of signal transduction and neuronal
      communication through the release of chemical transmitters from vesicles to the
      extracellular environment. Here, we use disk electrodes placed on top of PC12
      cells to show that treatment with barbiturate induces fewer molecules released
      during exocytosis and changes the event dynamics perhaps by inducing a less
      stable fusion pore that is prone to close faster during partial exocytosis.
      Larger events are essentially abolished. However, use of intracellular vesicle
      impact electrochemical cytometry using a nano-tip electrode inserted into a cell
      shows that the distribution of vesicle transmitter content does not change after
      barbiturate treatment. This indicates that barbiturate selectively alters the
      pore size of larger events or perhaps differentially between types of vesicles.
      Alteration of exocytosis in this manner could be linked to the effects of general
      anesthetics on memory loss.

PMID- 29356267
TI  - Cleavable Crosslinkers as Tissue Fixation Reagents for Proteomic Analysis.
AB  - Formaldehyde fixation is widely used for long-term maintenance of tissue.
      However, due to formaldehyde-induced crosslinks, fixed tissue proteins are
      difficult to extract, which hampers mass spectrometry (MS) proteomic analyses.
      Recent years have seen the use of different combinations of high temperature and
      solubilizing agents (usually derived from antigen retrieval techniques) to
      unravel formaldehyde-fixed paraffin-embedded tissue proteomes. However, to
      achieve protein extraction yields similar to those of fresh-frozen tissue, high
      temperature heating is necessary. Such harsh extraction conditions can affect
      sensitive amino acids and post-translational modifications, resulting in the loss
      of important information, while still not resulting in protein yields comparable
      to those of fresh-frozen tissue. Herein, the objective is to evaluate cleavable
      protein crosslinkers as fixatives that allow tissue preservation and efficient
      protein extraction from fixed tissue for MS proteomics under mild conditions.
      With this goal in mind, disuccinimidyl tartrate (DST) and
      dithiobis(succinimidylpropionate) (DSP) are investigated as cleavable fixating
      reagents. These compounds crosslink proteins by reacting with amino groups,
      leading to amide bond formation, and can be cleaved with sodium metaperiodate
      (cis-diols, DST) or reducing agents (disulfide bonds, DSP), respectively. Results
      show that cleavable protein crosslinking with DST and DSP allows tissue fixation
      with morphology preservation comparable to that of formaldehyde. In addition,
      cleavage of DSP improves protein recovery from fixed tissue by a factor of 18 and
      increases the number of identified proteins by approximately 20 % under mild
      extraction conditions compared with those of formaldehyde-fixed paraffin-embedded
      tissue. A major advantage of DSP is the introduction of well-defined protein
      modifications that can be taken into account during database searching. In
      contrast to DSP fixation, DST fixation followed by cleavage with sodium
      metaperiodate, although effective, results in side reactions that prevent
      effective protein extraction and interfere with protein identification. Protein
      crosslinkers that can be cleaved under mild conditions and result in defined
      modifications, such as DSP, are thus viable alternatives to formaldehyde as
      tissue fixatives to facilitate protein analysis from paraffin-embedded, fixed
      tissue.

PMID- 29356268
TI  - Stable Enantiomers Displaying Thermally Activated Delayed Fluorescence: Efficient
      OLEDs with Circularly Polarized Electroluminescence.
AB  - Aromatic-imide-based thermally activated delayed fluorescent (TADF) enantiomers,
      (+)-(S,S)-CAI-Cz and (-)-(R,R)-CAI-Cz, were efficiently synthesized by
      introducing a chiral 1,2-diaminocyclohexane to the achiral TADF unit. The TADF
      enantiomers exhibited high PLQYs of up to 98 %, small DeltaEST  values of 0.06
      eV, as well as obvious temperature-dependent transient PL spectra, thus
      demonstrating their excellent TADF properties. Moreover, the TADF enantiomers
      showed mirror-image CD and CPL activities. Notably, the CP-OLEDs with CPEL
      properties based on the TADF enantiomers not only achieved high EQE values of up
      to 19.7 and 19.8 %, but also displayed opposite CPEL signals with gEL  values of 
      1.7*10-3 and 2.3*10-3 , which represents the first CP-OLEDs, based on the
      enantiomerically pure TADF materials, having both high efficiencies and intense
      CPEL.

PMID- 29356269
TI  - Bioresorbable vascular scaffold versus everolimus-eluting stents or drug eluting
      balloon for the treatment of coronary in-stent restenosis: 1-Year follow-up of a
      propensity score matching comparison (the BIORESOLVE-ISR Study).
AB  - OBJECTIVES: to compare the 1-year outcome between bioresorbable vascular scaffold
      (BVS), everolimus-eluting stent (EES), and drug-eluting balloon (DEB) for in
      stent restenosis (ISR) treatment. BACKGROUND: BVS has been proposed as
      alternative for ISR treatment. To date a direct comparison between BVS and DES or
      DEB for ISR treatment is lacking. METHODS: We retrospectively analyzed all ISR
      lesions treated with BVS, DEB, and EES from January 2012 to December 2014. A
      total of 548 lesions (498 patients) were included. By applying two propensity
      score matching, 93 lesions treated with BVS were compared with 93 lesions treated
      with DEB, and 100 lesions treated with BVS were compared to 100 lesions treated
      with EES. RESULTS: At 1-year follow-up the incidence of device-oriented
      cardiovascular events (DOCE) and its components did not significantly differ
      between BVS and DEB (DOCE: 10.9 vs. 11.8%, HR, 0.91; 95% CI, 0.33-2.52; P = 0.86;
      Cardiac death: 2.2 vs. 1.2%, HR, 1.74, 95% CI 0.16-18.80, P = 0.65; ID-TLR: 8.9
      vs. 10.7%, HR, 0.81, 95% CI 0.27-2.48, P = 0.71; TV-MI: 3.3 vs. 1.2%, HR, 2.39,
      95% CI 0.27-21.32, P = 0.43) and BVS vs. EES (DOCE: 10.1 vs. 5.2% HR, 1.81, 95%
      CI, 0.63-5.25; P = 0.27; Cardiac death: 3.0 vs. 1.1%; HR, 2.83, 95% CI 0.29-27.4,
      P = 0.37; ID-TLR: 7.2 vs. 4.2%, HR, 1.57, 95% CI 0.47-5.23, P = 0.46; TV-MI: 3.1
      vs. 0%). CONCLUSION: At 1-year follow-up the use of BVS as ISR treatment is
      associated with a higher, even if not significant, DOCE rate compared with EES
      while a similar rate compared to DEB.

PMID- 29356270
TI  - Phytoplankton defence mechanisms: traits and trade-offs.
AB  - In aquatic ecosystems, unicellular algae form the basis of the food webs.
      Theoretical and experimental studies have demonstrated that one of the mechanisms
      that maintain high diversity of phytoplankton is through predation and the
      consequent evolution of defence mechanisms. Proposed defence mechanisms in
      phytoplankton are diverse and include physiological (e.g. toxicity,
      bioluminescence), morphological (e.g. silica shell, colony formation), and
      behavioural (e.g. escape response) traits. However, the function of many of the
      proposed defence mechanisms remains elusive, and the costs and benefits (trade
      offs) are often unquantified or undocumented. Here, we provide an overview of
      suggested phytoplankton defensive traits and review their experimental support.
      Wherever possible we quantify the trade-offs from experimental evidence and
      theoretical considerations. In many instances, experimental evidence suggests
      that defences are costless. However, we argue that (i) some costs materialize
      only under natural conditions, for example, sinking losses, or dependency on the
      availability of specific nutrients, and (ii) other costs become evident only
      under resource-deficient conditions where a rivalry for limiting resources
      between growth and defence occurs. Based on these findings, we suggest two
      strategies for quantifying the costs of defence mechanisms in phytoplankton: (i)
      for the evaluation of defence costs that are realized under natural conditions, a
      mechanistic understanding of the hypothesized component processes is required;
      and (ii) the magnitude of the costs (i.e. growth reduction) must be assessed
      under conditions of resource limitation.

PMID- 29356271
TI  - Assessment of the efficacy and tolerance of an innovative regenerative serum on
      cutaneous regeneration, following fractional laser procedure using Erbium:YAG.
AB  - INTRODUCTION: Cutaneous regeneration, fractional laser, medical device, cellular
      proliferation cutaneous changes linked to photoaging are currently treated with
      physical treatments, such as fractional laser, which may induce epidermal
      alteration. OBJECTIVE: To determine the efficacy and safety of a regenerative
      serum (Matricium(r) , Laboratoire Bioderma, France) after laser procedure.
      METHODS: Prospective, double-blind, controlled, and randomized study in subjects
      with photoaged skin. The regenerative serum of treatment was used after a
      fractional laser session twice daily for 2 months on 1 side of the face and the
      placebo on the other side. The main variable to determine efficacy was the
      improvement of clinical signs and histological and immunological results.
      RESULTS: A superior quality of epidermal regeneration on the treated side
      compared to the placebo side was observed. Likewise, a superior and faster
      clinical improvement on static wrinkles was observed on the hemiface on which the
      regenerative serum was used. After 60 days, the investigator and the subjects
      observed a moderate to significant improvement of the skin on the treated side
      and a mild to moderate improvement on the placebo side. Histological examinations
      showed a superior thickness of epidermis and higher cellular proliferation rate
      (Ki67 markers) as well as a superior thickness of dermis with higher increase in
      elastin density with the regenerative serum compared to placebo. CONCLUSION: The
      use of the regenerative serum after fractional laser on the face accelerated and
      improved the cutaneous regeneration on both the clinical and histological level
      and maximized the benefits of the laser procedure.

PMID- 29356272
TI  - Densely Packed, Ultra Small SnO Nanoparticles for Enhanced Activity and
      Selectivity in Electrochemical CO2 Reduction.
AB  - Controlling the selectivity in electrochemical CO2 reduction is an unsolved
      challenge. While tin (Sn) has emerged as a promising non-precious catalyst for
      CO2 electroreduction, most Sn-based catalysts produce formate as the major
      product, which is less desirable than CO in terms of separation and further use.
      Tin monoxide (SnO) nanoparticles supported on carbon black were synthesized and
      assembled and their application in CO2 reduction was studied. Remarkably high
      selectivity and partial current densities for CO formation were obtained using
      these SnO nanoparticles compared to other Sn catalysts. The high activity is
      attributed to the ultra-small size of the nanoparticles (2.6 nm), while the high
      selectivity is attributed to a local pH effect arising from the dense packing of
      nanoparticles in the conductive carbon black matrix.

PMID- 29356273
TI  - Unknown-onset strokes with anterior circulation occlusion treated by thrombectomy
      after DWI-FLAIR mismatch selection.
AB  - BACKGROUND AND PURPOSE: The DAWN trial recently showed compelling evidence in
      treating late window and wake-up stroke patients with thrombectomy using a
      clinical-imaging mismatch. The aim was to evaluate the results of thrombectomy
      for unknown-onset strokes (UOS) treated in our centres after a diffusion weighted
      imaging/fluid attenuated inversion recovery (DWI-FLAIR) mismatch based selection.
      METHODS: A multicentre, cohort study was performed of consecutive UOS treated by
      thrombectomy between 2012 and 2016. UOS with proximal anterior circulation
      occlusion discovered beyond 6 h from 'last seen normal' were compared with known
      onset strokes (KOS) for whom thrombectomy was started within 6 h from onset. Time
      intervals were recorded from first time found abnormal. Results were adjusted for
      age, diabetes, hypertension, National Institutes of Health Stroke Scale, site of
      occlusion, DWI Alberta Stroke Programme Early CT Score, intravenous thrombolysis
      and use of general anaesthesia. RESULTS: Amongst 1246 strokes with anterior
      circulation occlusion treated by thrombectomy, 277 were UOS, with a 'last time
      seen well' beyond 6 h and DWI-FLAIR mismatch, and 865 were KOS who underwent
      groin puncture within 6 h. Favourable outcome was achieved less often in UOS than
      KOS patients (45.2% vs. 53.9%, P = 0.022). After pre-specified adjustment, this
      difference was not significant (adjusted relative risk 0.91; 95% confidence
      interval 0.80-1.04; P = 0.17). No differences were found in secondary outcomes.
      Time intervals from first found abnormal were significantly longer in UOS.
      CONCLUSION: Thrombectomy of UOS with anterior circulation occlusion and DWI-FLAIR
      mismatch appears to be as safe and efficient as thrombectomy of KOS within 6 h
      from onset. This pattern of imaging could be used for patient selection when time
      of onset is unknown.

PMID- 29356274
TI  - Purpose-built national burns center: The Israeli experience.
AB  - The opening of the National Burns Center (NBC) in Sheba Medical Center (SMC) in
      2014 was a keystone point in the development of specialized burns trauma services
      for Israel to ensure burn care and disaster planning at international standards.
      The NBC is a purpose-built, level 1 burns trauma center that receives patients
      from Israel, Gaza, West Bank, and abroad. Hosting six intensive care and four
      step-down burns beds, the center serves as a referral center for patients in
      other health-care facilities with indication for hospitalization. In the present
      study, we describe the planning, design, and organization of the NBC at the SMC
      with reference to some of the key areas and considerations in its conception and
      development. With the improved survival rates of patients with extensive burns
      and the demographics and characteristics among burn-injury patients in Israel,
      the NBC has the capacity to be the center of excellence in burns care, teaching,
      and research within the Middle East.

PMID- 29356275
TI  - Cytological studies on the infection of rice root by Ustilaginoidea virens.
AB  - In recent years, false smut disease of rice has been one of the most important
      diseases of cultivated rice in China. Ustilaginoidea virens is an ascomycete
      fungal pathogen that causes false smut in rice. There is always controversy about
      whether the pathogen can infect the rice root and cause the occurrence of false
      smut, mainly due to lack direct cytological evidence. In our study, we observed
      the cytological structure of rice root invaded by U. virens. The results showed
      that U. virens could attach to the surface of young roots and penetrate into the
      intercellular space of the root epidermis. The cellulose microfibrils in root
      epidermal cell wall are very loose and soft, and their structural features are
      similar to filaments of rice. After the fungus infected the roots, a large number
      of fungal secretions were accumulated outside of the cell walls. At 40 days, the
      fungus began to degrade, but pathogens still had not infected the sclerenchyma,
      in which the cells are arranged densely and the cell walls are thicker. U. virens
      could not cross the sclerenchyma layer into the endodermis and phloem of the
      root. To some extent, the U. virens infection affected the leaf and root growth
      of the rice. After inoculation, there was no fungal mycelium found in transverse
      sections of the rice young stem. These results suggested that root colonization
      of U. virens does not lead to systemic invasion in rice.

PMID- 29356276
TI  - Influence of breathing patterns and orthostatic stress on postural control in
      older adults.
AB  - AIM: To investigate the influence of breathing patterns and blood pressure
      behavior postural control in older adults. METHODS: A total of 20 older adults
      carried out spontaneous, controlled (15 cycles/min) and deep (6 cycles/min)
      breathing trials, in random order. In this session, the heart rate was recorded
      continuously and blood pressure measured every 3 min. In addition, the challenge
      from sitting to an active standing position was carried out with eyes closed
      during 6 min on a baropodometer plate with electromyography recording. The root
      mean square (RMS) of electromyography was calculated. RESULTS: There were
      significant differences in the postural control with spontaneous breathing from
      the first minute (center of pressure [COP]-area 216.40 +/- 116.70 mm2 ) in
      comparison with the third minute (COP-area 79.35 +/- 68.11 mm2 ; d = 0.89; P <
      0.01) and the sixth minute (COP-area 70.24 +/- 41.26 mm2 ; d = 0.60; P < 0.05) of
      active standing. Furthermore, deep breathing significantly increases the COP-area
      (158.50 +/- 126.2 mm2 ) at the sixth minute of active standing in comparison with
      spontaneous breathing (70.24 +/- 41.26 mm2 ; d = 0.80; P < 0.01). There were also
      significant differences in systolic blood pressure during spontaneous breathing
      between the baseline measures (sitting position 123 +/- 11 mmHg) and the first
      minute of active standing (117 +/- 13 mmHg; d = 0.24; P < 0.05). Furthermore,
      electromyography activity of the tibialis anterior increased during the deep
      (17.52 +/- 9.21 RMS) and controlled breathing (16.75 +/- 5.26 RMS) compared with
      the spontaneous condition (14.93 +/- 5.56 RMS; d = 0.17; P < 0.05). CONCLUSIONS:
      The present data provide important insight into the respiratory and hemodynamics
      effects of postural control in older adults. The current data confirm that deep
      breathing causes periodic perturbation in the neuromuscular compensation of the
      lower limbs. Geriatr Gerontol Int 2018; 18: 692-697.

PMID- 29356277
TI  - Assessment of the efficacy of a new complex antisensitive skin cream.
AB  - BACKGROUND: Sensitive skin is frequently complaint in dermatology consultation
      with cutaneous manifestations such as stinging, redness, dryness, and burning
      sensation that affect the quality of life. Its pathogenesis is mainly related to
      dysfunction of neurosensory, skin barrier, and also immune activity. The
      treatment is generally based on continuous and topical therapy by nonirritating
      complex. OBJECTIVE: To evaluate the antisensitive function of a new complex cream
      composed by Yunnan Portulaca oleracea extract, Prinsepia utilis oil, beta-glucan,
      and sodium hyaluronate extracted from mushroom. METHODS: A randomized double
      blind and self-control study was conducted on 20 selected volunteers with
      sensitive skin. Subjects applied the test cream to 1 side of the face, and the
      control cream (tolerance-extreme cream) to the other side of the face, twice
      daily over 28 days. Evaluations were performed at baseline and at 28 days. Expert
      clinical grading of facial skin including dryness, roughness, desquamation, and
      erythema was assessed. Subject self-assessment questionnaires, digital
      photography and noninvasive bioinstrumentation of hydration, transepidermal water
      loss, lipid index, skin texture, and wettability were also included in the study.
      RESULTS: Products were well tolerated. For all parameters studied, no significant
      difference was observed between test and control creams. Results showed that test
      cream provided a statistically significant improvement in clinical grading scores
      for dryness, roughness, and erythema at 28 days compared to baseline. In
      addition, statistically significant improvement of skin hydration and texture
      parameters (eg, smoothness and roughness) was demonstrated. Volunteers'
      questionnaire revealed self-perceived benefits consistent with expert visual
      grading. CONCLUSION: This study confirmed the effectiveness and tolerance of the
      new complex cream in subjects with sensitive skin. The test cream could serve as
      a daily care moisturizer for face.

PMID- 29356278
TI  - Antiplatelet drug selection in PCI to vein grafts in patients with acute coronary
      syndrome and adverse clinical outcomes: Insights from the British Cardiovascular
      Intervention Society database.
AB  - OBJECTIVE: This study aims to evaluate outcomes associated with different P2Y12
      agents in Saphenous Vein graft (SVG) percutaneous coronary intervention (PCI).
      BACKGROUND: SVG PCI is associated with greater risks of ischemic complications,
      compared with native coronary PCI. Outcomes associated with the use of potent
      P2Y12 blocking drugs, Prasugrel and Ticagrelor, in SVG PCI are unknown. METHODS:
      Patients included in the study underwent SVG PCI in the United Kingdom between
      2007 and 2014 for acute coronary syndrome and were grouped by P2Y12 antiplatelet
      use. In-hospital major adverse cardiac events, major bleeding and 30-day and 1
      year mortality were examined. Multiple imputations with chained equations to
      impute missing data were used. Adjustment for baseline imbalances was performed
      using (1) multiple logistic regression (MLR) and (separately) (2) propensity
      score matching (PSM). RESULTS: Data weres analyzed from 8,119 patients and most
      cases were treated with Clopidogrel (n = 7,401), followed by Ticagrelor (n = 497)
      and Prasugrel (n = 221). In both MLR and PSM models, there was no significant
      evidence to suggest that either Prasugrel or Ticagrelor was associated with
      significantly lower 30-day mortality compared with Clopidogrel. The odds ratios
      reported from the multivariable analysis were 1.22 (95% CI: 0.60-2.51) for
      Prasugrel vs. Clopidogrel and 0.48 (95% CI: 0.20-1.16) for Ticagrelor vs.
      Clopidogrel. No significant differences were seen for in-hospital ischemic or
      bleeding events. CONCLUSIONS: Our real world national study provides no clear
      evidence to indicate that use of potent P2Y12 blockers in SVG PCI is associated
      with improved clinical outcomes.

PMID- 29356279
TI  - On the Synthesis of Chocolate Flavonoids (Propanols, Butanals) in the
      Interstellar Medium.
AB  - Complex organic molecules are ubiquitous in star- and planet-forming regions as
      well as on comets such as on 67P/Churyumov-Gerasimenko, but their origins have
      remained largely unexplained until now. Here, we report the first laboratory
      detection of distinct C3 H8 O (propanol, methyl ethyl ether) and C4 H8 O (n
      butanal, i-butanal) isomers formed within interstellar analog ices through
      interaction with ionizing radiation. This study reveals that complex organics
      with propyl (C3 H7 ) and butyl (C4 H9 ) groups can be synthesized easily in deep
      space and may act as key evolutionary tracers of a cosmic ray driven non
      equilibrium chemistry in low temperature interstellar ices at 10 K. These
      processes are of vital importance in initiating a chain of chemical reactions
      leading to complex organics-some of which are responsible for the flavors of
      chocolate-not only in the interstellar medium, but also on comet 67P/Churyumov
      Gerasimenko.

PMID- 29356280
TI  - Potential role of potassium and chloride channels in regulation of silymarin
      induced apoptosis in Candida albicans.
AB  - Silymarin, which is derived from the seeds of Silybum marianum, has been widely
      used to prevent and treat liver diseases. In our previous study, we reported that
      at concentrations above the minimal inhibitory concentration (MIC), silymarin
      exhibited antifungal activity against Candida albicans by targeting its plasma
      membrane. However, the antifungal mechanism at concentration below the MIC
      remains unknown. Therefore, we aimed to determine the underlying mechanism of
      antifungal effects of silymarin at concentration below the MIC. To evaluate the
      inhibitory effects on the ion channels, C. albicans cells were separately
      pretreated with potassium and chloride channel blockers. The antifungal activity
      of silymarin at sub-MIC was affected by the ion channel blockers. Potassium
      channel blockade inhibited the antifungal effects, whereas chloride channel
      blockade slightly enhanced these effects. Subsequently, we found that silymarin
      induced disturbances in calcium homeostasis via the cytosolic and mitochondrial
      accumulation of calcium. Furthermore, apoptotic responses, such as
      phosphatidylserine exposure, loss of mitochondrial membrane potential (MMP), DNA
      damage, and caspase activation were induced in response to silymarin treatment.
      The increases in intracellular calcium level and pro-apoptotic changes were
      prevented when potassium ion channels were blocked. In contrast, these changes
      were enhanced upon chloride channels blockade; however, this did not affect the
      intracellular calcium levels and MMP loss. Thus, we showed that silymarin
      treatment at concentration below the MIC induced apoptosis in C. albicans;
      additionally, ion channels contributed these effects. (c) 2018 IUBMB Life,
      70(3):197-206, 2018.

PMID- 29356281
TI  - Episode forecasting in bipolar disorder: Is energy better than mood?
AB  - OBJECTIVE: Bipolar disorder is a severe mood disorder characterized by
      alternating episodes of mania and depression. Several interventions have been
      developed to decrease high admission rates and high suicides rates associated
      with the illness, including psychoeducation and early episode detection, with
      mixed results. More recently, machine learning approaches have been used to aid
      clinical diagnosis or to detect a particular clinical state; however,
      contradictory results arise from confusion around which of the several
      automatically generated data are the most contributory and useful to detect a
      particular clinical state. Our aim for this study was to apply machine learning
      techniques and nonlinear analyses to a physiological time series dataset in order
      to find the best predictor for forecasting episodes in mood disorders. METHODS:
      We employed three different techniques: entropy calculations and two different
      machine learning approaches (genetic programming and Markov Brains as
      classifiers) to determine whether mood, energy or sleep was the best predictor to
      forecast a mood episode in a physiological time series. RESULTS: Evening energy
      was the best predictor for both manic and depressive episodes in each of the
      three aforementioned techniques. This suggests that energy might be a better
      predictor than mood for forecasting mood episodes in bipolar disorder and that
      these particular machine learning approaches are valuable tools to be used
      clinically. CONCLUSIONS: Energy should be considered as an important factor for
      episode prediction. Machine learning approaches provide better tools to forecast
      episodes and to increase our understanding of the processes that underlie mood
      regulation.

PMID- 29356282
TI  - Manipulating Band Structure through Reconstruction of Binary Metal Sulfide for
      High-Performance Thermoelectrics in Solution-Synthesized Nanostructured Bi13 S18
      I2.
AB  - Reconstructing canonical binary compounds by inserting a third agent can
      significantly modify their electronic and phonon structures. Therefore, it has
      inspired the semiconductor communities in various fields. Introducing this
      paradigm will potentially revolutionize thermoelectrics as well. Using a solution
      synthesis, Bi2 S3 was rebuilt by adding disordered Bi and weakly bonded I. These
      new structural motifs and the altered crystal symmetry induce prominent changes
      in electrical and thermal transport, resulting in a great enhancement of the
      figure of merit. The as-obtained nanostructured Bi13 S18 I2 is the first non
      toxic, cost-efficient, and solution-processable n-type material with z T=1.0.

PMID- 29356283
TI  - Intrahepatic plexiform neurofibroma with neurofibromatosis type 1.

PMID- 29356284
TI  - Addressing respiratory tract diseases: Our way forward.

PMID- 29356285
TI  - Response to ponatinib before hematopoietic stem cell transplantation in a child
      with relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia.

PMID- 29356286
TI  - Medical equipment deployment in pediatric emergency prehospital medical units in
      Japan.
AB  - The deployment status of pediatric emergency equipment in ambulances in Japan is
      unknown. To investigate the status of and issues associated with prehospital
      emergency medical care for pediatric patients, we conducted a descriptive
      epidemiological study. We carried out a Web-based survey of 767 fire defense
      headquarters in Japan, of which 671 responded (valid response rate, 88%). Most of
      the fire defense headquarters equipped all of their ambulances with oxygen masks
      (82%), bag-valve masks (for neonates, 83%; for children, 84%), straight
      laryngoscope blades (for neonates, 47%; for children 68%), blood pressure cuffs
      for children (91%), oximeter probes (78%), and stiff neck collars (91%); but
      despite the need for other equipment such as nasopharyngeal and oropharyngeal
      airways, and Magill forceps, they were insufficiently deployed. In Japan,
      prehospital emergency medical equipment deployment does not meet the needs of
      pediatric patients. Minimum equipment standards need to be established for
      pediatric prehospital care.

PMID- 29356287
TI  - Acute lymphoblastic leukemia with hypereosinophilia in a 3-year-old boy.

PMID- 29356288
TI  - Congenital abdominal aortic aneurysm discovered incidental to a lower back mass.

PMID- 29356290
TI  - Three-dimensional computed tomography of congenital pulmonary airway
      malformation.

PMID- 29356289
TI  - X-linked agammaglobulinemia complicated with pulmonary aspergillosis.

PMID- 29356293
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 5/2018.

PMID- 29356291
TI  - Blood flow restriction and cuff width: effect on blood flow in the legs.
AB  - : Much of the literature examining blood flow restriction in the lower body uses
      cuffs of differing widths. It is currently unknown whether similar relative
      pressures using cuffs of differing widths elicit the same blood flow response.
      PURPOSE: To examine the hemodynamic responses to relative pressures using two
      commonly used cuffs (10 and 12 cm). METHODS: In a random order over two
      laboratory visits, one cuff was applied to the right proximal thigh of the
      participant (men = 17, women = 14), and arterial occlusion pressure (AOP) was
      measured. Ultrasound measures of blood flow, mean blood velocity, peak blood
      velocity and artery diameter were taken from the posterior tibial artery at rest
      and during the application of 10% increments of the AOP. RESULTS: There was no
      significant difference between the 10- and 12-cm cuff relating to blood flow (
      0.501 ml min-1 , SD 7.9, P = 0.728), mean blood velocity (-0.168 cm s-1 , SD 1.7,
      P = 0.590), peak blood velocity (0.586 cm s-1 , SD 11.7, P = 0.783) or artery
      diameter (0.003 cm, SD 0.02, P = 0.476). There was a main effect of pressure for
      blood flow (P<0.0005), mean blood velocity (P<0.0005), peak blood velocity
      (P<0.0005) and artery diameter (P = 0.005), with each decreasing with increasing
      pressures. Peak blood velocity increased to 60% of AOP before decreasing with
      increased pressure. CONCLUSION: As long as relative pressures are applied, cuff
      width appears to have little to no effect on the blood flow stimulus during blood
      flow restriction at rest.

PMID- 29356294
TI  - Catalytic Gas-Phase Production of Lactide from Renewable Alkyl Lactates.
AB  - A new route to lactide, which is a key building block of the bioplastic
      polylactic acid, is proposed involving a continuous catalytic gas-phase
      transesterification of renewable alkyl lactates in a scalable fixed-bed setup.
      Supported TiO2 /SiO2 catalysts are highly selective to lactide, with only minimal
      lactide racemization. The solvent-free process allows for easy product separation
      and recycling of unconverted alkyl lactates and recyclable lactyl intermediates.
      The catalytic activity of TiO2 /SiO2 catalysts was strongly correlated to their
      optical properties by DR UV/Vis spectroscopy. Catalysts with high band-gap energy
      of the supported TiO2 phase, indicative of a high surface spreading of isolated
      Ti centers, show the highest turnover frequency per Ti site.

PMID- 29356295
TI  - To share or not to share...incentivizing data sharing in life science
      communities.
AB  - Most scientists recognize the importance of sharing data online in an open
      fashion. Nonetheless, many studies have documented the concerns that accompany
      data sharing activities, including loss of credit or IP, misuse and the time
      needed to curate interoperable data. To this end, discussions around data sharing
      often identify incentives that could potentially ameliorate these
      disincentivising concerns. Nonetheless, current Open Data discussions often rely
      on evidence-based studies to identify the disincentives to overcome. This results
      in highly specific and directed interventions. In contrast, this paper offers a
      different interpretation of these concerns. To do so, it makes use of the Thomas
      Theorem which suggests that: "If men define situations as real, they are real in
      their consequences". Using empirical evidence from sub-Saharan African
      (bio)chemistry laboratories, this paper illustrates how individual perceptions of
      research environments - whether associated with evidence or not - are highly
      influential in shaping data sharing practices. It concludes with the suggestion
      that discussion on incentivising data sharing amongst scientific communities need
      to take a broader set of concerns into account and offer a more creative approach
      to ameliorating environmental disincentives.

PMID- 29356296
TI  - Beyond pathways: genetic dissection of tocopherol content in maize kernels by
      combining linkage and association analyses.
AB  - Although tocopherols play an important role in plants and animals, the genetic
      architecture of tocopherol content in maize kernels has remained largely unknown.
      In this study, linkage and association analyses were conducted to examine the
      genetic architecture of tocopherol content in maize kernels. Forty-one unique
      quantitative trait loci (QTLs) were identified by linkage mapping in six
      populations of recombinant inbred lines (RILs). In addition, 32 significant loci
      were detected via genome-wide association study (GWAS), 18 of which colocalized
      with the QTLs identified by linkage mapping. Fine mapping of a major QTL
      validated the accuracy of GWAS and QTL mapping results and suggested a role for
      nontocopherol pathway genes in the modulation of natural tocopherol variation. We
      provided genome-wide evidence that genes involved in fatty acid metabolism,
      chlorophyll metabolism and chloroplast function may affect natural variation in
      tocopherols. These findings were confirmed through mutant analysis of a
      particular gene from the fatty acid pathway. In addition, the favourable alleles
      for many of the significant SNPs/QTLs represented rare alleles in natural
      populations. Together, our results revealed many novel genes that are potentially
      involved in the variation of tocopherol content in maize kernels. Pyramiding of
      the favourable alleles of the newly elucidated genes and the well-known
      tocopherol pathway genes would greatly improve tocopherol content in maize.

PMID- 29356297
TI  - Understanding the roles of glutamine synthetase, glutaminase, and glutamate
      decarboxylase autoantibodies in imbalanced excitatory/inhibitory
      neurotransmission as etiological mechanisms of autism.
AB  - AIM: Autism is a heterogeneous neurological disorder that is characterized by
      impairments in communication and social interactions, repetitive behaviors, and
      sensory abnormalities. The etiology of autism remains unclear. Animal, genetic,
      and post-mortem studies suggest that an imbalance exists in the neuronal
      excitation and inhibition system in autism. The aim of this study was to
      determine whether alterations of the measured parameters in children with autism
      are significantly associated with the risk of a sensory dysfunction. METHODS: The
      glutamine synthetase (GS), kidney-type glutaminase (GLS1), and glutamic acid
      decarboxylase autoantibody levels were analyzed in 38 autistic children and 33
      age- and sex-matched controls using enzyme-linked immunosorbent assays. RESULTS:
      The obtained data demonstrated significant alterations in glutamate and glutamine
      cycle enzymes, as represented by GS and GLS1, respectively. While the glutamic
      acid decarboxylase autoantibodies levels were remarkably increased, no
      significant difference was observed compared to the healthy control participants.
      CONCLUSION: The obtained data indicate that GS and GLS1 are promising indicators
      of a neuronal excitation and inhibition system imbalance and that combined
      measured parameters are good predictive biomarkers of autism.

PMID- 29356298
TI  - Heterozygosis in aromatic amino acid decarboxylase deficiency: Evidence for a
      positive interallelic complementation between R347Q and R358H mutations.
AB  - Aromatic amino acid or Dopa decarboxylase (AADC or DDC) is a homodimeric
      pyridoxal 5'-phosphate (PLP) enzyme responsible for the generation of the
      neurotransmitters dopamine and serotonin. AADC deficiency is a rare inborn
      disease caused by mutations of the AADC gene leading to a defect of AADC enzyme
      and resulting in impaired dopamine and serotonin synthesis. Until now, only the
      molecular effects of homozygous mutations were analyzed. However, although
      heterozygous carriers of AADC deficiency were identified, the molecular aspects
      of their enzymatic phenotypes are not yet investigated. Here, we focus our
      attention on the R347Q/R358H and R347Q/R160W heterozygous mutations, and report
      for the first time the isolation and characterization, in the purified
      recombinant form, of the R347Q/R358H heterodimer and of the R358H homodimer. The
      results, integrated with those already known of the R347Q homodimeric variant,
      provide evidence that (i) the R358H mutation strongly reduces the PLP-binding
      affinity and the catalytic activity, and (ii) a positive interallelic
      complementation exists between the R347Q and the R358H mutations. Bioinformatics
      analyses provide the structural basis for these data. Unfortunately, the
      R347Q/R160W heterodimer was not obtained in a sufficient amount to allow its
      purification and characterization. Nevertheless, the biochemical features of the
      R160W homodimer give a contribution to the enzymatic phenotype of the
      heterozygous R347Q/R160W and suggest the possible relevance of Arg160 in the
      proper folding of human DDC. (c) 2018 IUBMB Life, 70(3):215-223, 2018.

PMID- 29356299
TI  - Testosterone a key factor in gender related metabolic syndrome.
AB  - Metabolic syndrome (MetS) is highly correlated with cardiovascular diseases.
      Although an excess of body fat is a determinant factor for MetS development, a
      reduced level of testosterone plays a fundamental role in its regulation. Low
      testosterone level is highly related to insulin resistance, visceral obesity and
      MetS. We have searched in Pubmed clinical trial with the password: testosterone
      and insulin resistance, and testosterone and MetS. We found 19 studies on the
      correlation between testosterone level with insulin resistance and 18 on the
      effect of testosterone therapy on MetS. A high correlation between low
      testosterone and insulin resistance has been found in men, but not in women.
      Testosterone administration in hypogonadal men improved MetS and reduced the
      mortality risk. Androgen and oestrogen receptors are expressed in adipocytes,
      muscle and liver tissue, and their activation is necessary to improve metabolic
      control. Normalization of testosterone level should be the primary treatment in
      men, along with caloric restriction and physical exercise. These findings come
      mainly from correlative data, and there remains a need for randomized trials to
      strengthen this evidence. This review will consider the effects of testosterone
      on the regulation and development of MetS in men and women.

PMID- 29356300
TI  - Pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic
      syndrome.
AB  - Thrombotic microangiopathies are rare disorders characterized by the concomitant
      occurrence of severe thrombocytopenia, microangiopathic hemolytic anemia, and a
      variable degree of ischemic end-organ damage. The latter particularly affects the
      brain, the heart, and the kidneys. The primary forms, thrombotic thrombocytopenic
      purpura (TTP) and hemolytic uremic syndrome (HUS), although their clinical
      presentations often overlap, have distinctive pathophysiologies. TTP is the
      consequence of a severe ADAMTS-13 deficiency, either immune-mediated as a result
      of circulating autoantibodies, or caused by mutations in ADAMTS-13. HUS develops
      following an infection with Shiga-toxin producing bacteria, or as the result of
      excessive activation of the alternative pathway of the complement system because
      of mutations in genes encoding complement system proteins.

PMID- 29356302
TI  - Fast publication, a must for a journal.
AB  - As Diabetes/Metabolism: Research & Reviews (DMRR) begins its transition to a new
      editorial team, incoming Editor-in-Chief, Dr Paolo Pozzilli, reflects on the
      lessons learned from the past editorship and envisions the future of the journal.
      In today's fast-paced world, a medical journal should be fast in communicating
      decisions. Authors are eager to publish their work as fast as possible, and a
      journal must guarantee this, whilst at the same time ensuring a rigorous peer
      review process. With this in mind, we hope to help the diabetes scientific
      community.

PMID- 29356303
TI  - Rapid drink challenge test during esophageal high resolution manometry in
      patients with esophago-gastric junction outflow obstruction.
AB  - BACKGROUND: Esophago-gastric junction (EGJ) outflow obstruction is of unclear
      significance. Rapid drink challenge (RDC) test is easy to perform during
      esophageal high resolution manometry. We aimed to assess the yield of RDC test in
      patients with EGJ outflow obstruction. METHODS: Manometry studies of patients
      with EGJ outflow obstruction according to the Chicago Classification v3.0 were
      retrospectively reviewed. Pan-esophageal pressurization (PEP), esophageal
      shortening, and pressure gradient across the EGJ were analyzed during RDC test
      (200-mL free drinking in sitting position) and compared according to the causes
      of EGJ outflow obstruction determined by charts review. KEY RESULTS: Seventy-five
      patients (29 males, mean age 62 years) were included. Causes of EGJ outflow
      obstruction were previous esophago-gastric surgery (40%), incomplete form of
      achalasia (7%), mediastinal neoplasia (7%), other associated conditions (21%),
      and undetermined (25%). Rapid drink challenge test was successfully performed in
      70 patients and associated with PEP and shortening in 41% and 13%, respectively.
      The causes of EGJ outflow obstruction were similarly distributed in patients with
      and without PEP during RDC test. Esophageal shortening tended to be more likely
      in patients with definitive findings of obstruction (achalasia, previous surgery,
      neoplasia) than in the others. Dysphagia was more severe in patients with PEP
      and/or shortening during RDC test compared to those without. CONCLUSIONS &
      INFERENCES: Pan-esophageal pressurization and esophageal shortening were
      associated with symptoms severity but did not predict the cause of this disorder.
      Further prospective studies are necessary to determine if RDC test could help to
      select patients who might benefit from treatment.

PMID- 29356304
TI  - Fast image-based mitral valve simulation from individualized geometry.
AB  - BACKGROUND: Common surgical procedures on the mitral valve of the heart include
      modifications to the chordae tendineae. Such interventions are used when there is
      extensive leaflet prolapse caused by chordae rupture or elongation. Understanding
      the role of individual chordae tendineae before operating could be helpful to
      predict whether the mitral valve will be competent at peak systole. Biomechanical
      modelling and simulation can achieve this goal. METHODS: We present a method to
      semi-automatically build a computational model of a mitral valve from micro CT
      (computed tomography) scans: after manually picking chordae fiducial points, the
      leaflets are segmented and the boundary conditions as well as the loading
      conditions are automatically defined. Fast finite element method (FEM) simulation
      is carried out using Simulation Open Framework Architecture (SOFA) to reproduce
      leaflet closure at peak systole. We develop three metrics to evaluate simulation
      results: (i) point-to-surface error with the ground truth reference extracted
      from the CT image, (ii) coaptation surface area of the leaflets and (iii) an
      indication of whether the simulated closed leaflets leak. RESULTS: We validate
      our method on three explanted porcine hearts and show that our model predicts the
      closed valve surface with point-to-surface error of approximately 1 mm, a
      reasonable coaptation surface area, and absence of any leak at peak systole
      (maximum closed pressure). We also evaluate the sensitivity of our model to
      changes in various parameters (tissue elasticity, mesh accuracy, and the
      transformation matrix used for CT scan registration). We also measure the
      influence of the positions of the chordae tendineae on simulation results and
      show that marginal chordae have a greater influence on the final shape than
      intermediate chordae. CONCLUSIONS: The mitral valve simulation can help the
      surgeon understand valve behaviour and anticipate the outcome of a procedure.

PMID- 29356305
TI  - Monitoring Dissociation Kinetics during Electrophoretic Focusing to Enable High
      Specificity Nucleic Acid Detection.
AB  - A wide range of medical conditions can be diagnosed through sequence-specific
      analysis of nucleic acids. However, a major challenge remains in detecting a
      specific target in samples containing a high concentration of mismatching
      sequences. A single-step kinetic homogenous (free solution) assay is presented in
      which free sequence-specific probes are continuously separated from probe-target
      hybrids during electrophoretic sample focusing, allowing monitoring of
      dissociation kinetics. Under these conditions, the different kinetics of targets
      versus mismatches result in distinct patterns of the signal (for example, linear
      increase for target versus exponential decay for mismatch), allowing the
      detection of desired sequences even in the presence of high background nucleic
      acid content. Additionally, an analytical model provides insight into the
      underlying dynamics, and allows design of assays based on this mechanism.

PMID- 29356306
TI  - Evidence of interaction between genes in the folate/homocysteine metabolic
      pathway in controlling risk of non-syndromic oral cleft.
AB  - OBJECTIVE: Little consistent evidence is available for the association between
      the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and any
      of the individual genes in the folate/homocysteine metabolic pathway. We
      investigated the genes in the folate pathway to further clarify its potential
      influence on the risk of NSCL/P considering gene-gene (G*G) interaction. SUBJECTS
      AND METHODS: We selected markers in 18 genes from the pathway and applied
      Cordell's method to test for G*G interaction using 1,908 NSCL/P case-parent trios
      ascertained in an international consortium where a genomewide association study
      (GWAS) of oral clefts was conducted. RESULTS: We found intriguing signals among
      Asian and European ancestry groups for G*G interaction between markers in betaine
      homocysteine methyltransferase gene (BHMT/BHMT2) and dimethylglycine
      dehydrogenase gene (DMGDH) attaining genomewide significance. In the pooled data,
      the top significant interaction was found between rs13158309 (BHMT) and
      rs10514154 (DMGDH, p = 1.45 * 10-12 ). CONCLUSIONS: Our study illustrated the
      importance of taking into account potential G*G interaction for genetic
      association analysis in NSCL/P, and this study suggested both BHMT/BHMT2 and
      DMGDH should be considered as candidate genes for NSCL/P in future studies.

PMID- 29356307
TI  - Carotid artery stenting followed by open heart surgery in 323 patients: One-year
      results and influencing factors.
AB  - OBJECTIVES: The purpose of this study was to evaluate 1-year results and
      influencing factors of carotid artery stenting (CAS) before open heart surgery
      (OHS). BACKGROUND: Currently, the clinical outcomes and influencing factors of
      CAS followed by OHS still remain controversial. METHODS: Three hundred twenty
      three consecutive patients scheduled for CAS and OHS were enrolled in this study.
      The primary endpoint was a composite of major stroke, myocardial infarction, or
      death within 1 year after CAS. RESULTS: The incidence of the primary endpoint was
      5.6% (18/323). The Cox regression analysis revealed that an interval of <=5 days
      between CAS and OHS (HR, 4.85, 95% CI, 1.87-12.58; P = 0.001), congestive heart
      failure (HR, 4.08, 95% CI, 1.45-11.51; P = 0.008), and renal insufficiency (HR,
      4.56, 95% CI, 1.28-16.32; P = 0.020) could independently predict the incidence of
      the primary endpoint. The rate of the primary endpoint from CAS to 30 days after
      OHS was 4.6% (15/323). An interval of <=5 days between CAS and OHS (OR, 4.51, 95%
      CI, 1.52-13.36; P = 0.007) and congestive heart failure (OR, 5.32, 95% CI, 1.63
      17.43; P = 0.006) were identified as independent risk factors for the primary
      endpoint rate from CAS to 30 days after OHS by logistic regression analysis.
      CONCLUSIONS: CAS followed by OHS is a safe and effective treatment for patients
      with concomitant carotid and cardiac disease within 1-year follow up. The
      interval between CAS and OHS, congestive heart failure, and renal insufficiency
      could obviously influence the 1-year results.

PMID- 29356309
TI  - Direct Assessment of the Toxicity of Molybdenum Disulfide Atomically Thin Film
      and Microparticles via Cytotoxicity and Patch Testing.
AB  - The low toxicity of molybdenum disulfide (MoS2 ) atomically thin film and
      microparticles is confirmed via cytotoxicity and patch testing in this report.
      The toxicity of MoS2 thin film and microparticles is extensively studied but is
      still inconclusive due to potential organic contamination in the preparations of
      samples. Such contamination is avoided here through preparing MoS2 atomically
      thin film via direct sulfurization of molybdenum thin film on quartz plate, which
      permits a direct assessment of its toxicity without any contamination. Six
      different types of cells, including normal, cancer, and immortal cells, are
      cultured in the media containing MoS2 thin film on quartz plates or dispersed
      MoS2 microparticles and their viability is evaluated with respect to the
      concentrations of samples. Detached thin films from the quartz plates are also
      investigated to estimate the toxicity of dispersed MoS2 in biological media.
      Allergy testing on skin of guinea pigs is also conducted to understand their
      effect on animal skins. By avoiding possible organic contamination, the low
      toxicity of MoS2 atomically thin film and microparticles to cells and animal
      skins paves the way for its applications in flexible biosensing/bioimaging
      devices and biocompatible coatings.

PMID- 29356308
TI  - High number of PD-1 positive intratumoural lymphocytes predicts survival benefit
      of cytokine-induced killer cells for hepatocellular carcinoma patients.
AB  - BACKGROUND & AIMS: Adjuvant cytokine-induced killer (CIK) cells treatment has
      shown potential in reducing the recurrence rate and prolonging the survival of
      patients with hepatocellular carcinoma (HCC). We aimed to identify the best
      predictive biomarker for adjuvant CIK cells treatment in patients with HCC after
      curative resection. METHODS: This study retrospectively included 145 pairs of HCC
      patients by one-to-one propensity score matching. One group received CIK cells
      transfusion after surgery (surgery-CIK group); the other one group underwent
      surgery only (surgery-only group). Immunohistochemistry (IHC) was used to measure
      PD-1, PD-L1, CD4, CD8 and Foxp3 expression in tumour tissues of surgery-CIK
      group; IHC of PD-1 and PD-L1 was conducted in the surgery-only group. RESULTS:
      The surgery-CIK group had a significantly higher disease-free survival (DFS) and
      overall survival (OS) rates compared to the surgery-only group. Of all the
      intratumoural biomarkers, in the surgery-CIK group, multivariate analysis showed
      that a high number of PD-1+ tumour infiltrative lymphocytes (TILs) was the only
      factor that independently predicted favourable OS and DFS. By contrast, in the
      surgery-only group, no significant correlations between PD-1/PD-L1 expression and
      survival of patients were identified. Further correlation analysis showed a high
      number of PD-1+ TILs associated with a high number of both CD4+ and CD8+ TILs in
      surgery-CIK group. CONCLUSIONS: A high number of PD-1+ TILs can serve as a potent
      biomarker for adopting CIK cells therapy in HCC patients after curative
      resection.

PMID- 29356310
TI  - Adaptive evolution in the coccolithophore Gephyrocapsa oceanica following 1,000
      generations of selection under elevated CO2.
AB  - Coccolithophores are important oceanic primary producers not only in terms of
      photosynthesis but also because they produce calcite plates called coccoliths.
      Ongoing ocean acidification associated with changing seawater carbonate chemistry
      may impair calcification and other metabolic functions in coccolithophores. While
      short-term ocean acidification effects on calcification and other properties have
      been examined in a variety of coccolithophore species, long-term adaptive
      responses have scarcely been documented, other than for the single species
      Emiliania huxleyi. Here, we investigated the effects of ocean acidification on
      another ecologically important coccolithophore species, Gephyrocapsa oceanica,
      following 1,000 generations of growth under elevated CO2 conditions (1,000
      MUatm). High CO2 -selected populations exhibited reduced growth rates and
      enhanced particulate organic carbon (POC) and nitrogen (PON) production, relative
      to populations selected under ambient CO2 (400 MUatm). Particulate inorganic
      carbon (PIC) and PIC/POC ratios decreased progressively throughout the selection
      period in high CO2 -selected cell lines. All of these trait changes persisted
      when high CO2 -grown populations were moved back to ambient CO2 conditions for
      about 10 generations. The results suggest that the calcification of some
      coccolithophores may be more heavily impaired by ocean acidification than
      previously predicted based on short-term studies, with potentially large
      implications for the ocean's carbon cycle under accelerating anthropogenic
      influences.

PMID- 29356311
TI  - Resident and facility characteristics associated with care-need level
      deterioration in long-term care welfare facilities in Japan.
AB  - AIM: To determine the resident and facility characteristics associated with
      residents' care-need level deterioration in long-term care welfare facilities in
      Japan. METHODS: A nationally representative sample of 358 886 residents who lived
      in 3774 long-term care welfare facilities for at least 1 year from October 2012
      was obtained from long-term care insurance claims data. Facility characteristics
      were linked with a survey of institutions and establishments for long-term care
      in 2012. We used a multilevel logistic regression according to the inclusion and
      exclusion of lost to follow-up to define the resident and facility
      characteristics associated with resident care-need level deteriorations (lost to
      follow-up: the majority were hospitalized residents or had died; were treated as
      deterioration in the including loss to follow-up model). RESULTS: Adjusting for
      the covariates, at the resident level, older age and lower care-need level at
      baseline were more likely to show deterioration in the care-need level. At the
      facility level, metropolitan facilities, unit model (all private room settings)
      and mixed-model facilities (partly private room settings) were less likely to
      experience care-need level deterioration. A higher proportion of registered
      nurses among all nurses was negatively related to care-need level deterioration
      only in the model including lost to follow-up. A higher proportion of registered
      dietitians among all dietitians and the facilities in business for fewer years
      were negatively associated with care-need level deterioration only in the model
      excluding lost to follow-up. CONCLUSIONS: The present study could help identify
      residents who are at risk of care-need level deterioration, and could contribute
      to improvements in provider quality performance and enhance competence in the
      market. Geriatr Gerontol Int 2018; 18: 758-766.

PMID- 29356312
TI  - Cenicriviroc, a cytokine receptor antagonist, potentiates all-trans retinoic acid
      in reducing liver injury in cholestatic rodents.
AB  - BACKGROUND & AIMS: Cholestatic liver injury is mediated by bile acid-induced
      inflammatory responses. We hypothesized that superior therapeutic effects might
      be achieved by combining treatments that reduce the bile acid pool size with one
      that blocks inflammation. METHODS: Bile duct-ligated (BDL) rats and Mdr2(Abcb4)-/
      mice were treated with all-trans retinoic acid (atRA), a potent inhibitor of
      bile acid synthesis, 5 mg/kg/d by gavage, or Cenicriviroc (CVC), a known
      antagonist of CCR2 and CCR5, 50 mg/kg/d alone or in combination for 14 days and 1
      month respectively. RESULTS: All-trans retinoic acid alone reduced bile acid pool
      size and liver necrosis in BDL rats. However, the combination with CVC further
      reduced liver to body weight ratio, bile acid pool size, plasma liver enzyme,
      bilirubin, liver necrosis and fibrosis when compared to the atRA treatment. The
      assessment of hepatic hydroxyproline content further confirmed the reduced liver
      injury concurrent with reduction of pro-inflammatory cytokines emphasizing the
      synergistic effects of these two agents. Profiling of hepatic inflammatory cells
      revealed that combination therapy reduced neutrophils and T cells but not
      macrophages. The superior therapeutic effects of combination treatment were also
      confirmed in Mdr2-/- mice where a significant reduction in plasma liver enzymes,
      bilirubin, liver fibrosis, bile duct proliferation and hepatic infiltration of
      neutrophils and T cells and expression of cytokines were found. CONCLUSIONS:
      Multitargeted therapy is an important paradigm for treating cholestatic liver
      injury. The combination of CVC with atRA or other FXR activators may warrant a
      clinical trial in patients with cholestatic liver disease.

PMID- 29356313
TI  - Electrocatalytic N-Doped Graphitic Nanofiber - Metal/Metal Oxide Nanoparticle
      Composites.
AB  - Carbon-based nanocomposites have shown promising results in replacing commercial
      Pt/C as high-performance, low cost, nonprecious metal-based oxygen reduction
      reaction (ORR) catalysts. Developing unique nanostructures of active components
      (e.g., metal oxides) and carbon materials is essential for their application in
      next generation electrode materials for fuel cells and metal-air batteries.
      Herein, a general approach for the production of 1D porous nitrogen-doped
      graphitic carbon fibers embedded with active ORR components, (M/MOx , i.e., metal
      or metal oxide nanoparticles) using a facile two-step electrospinning and
      annealing process is reported. Metal nanoparticles/nanoclusters nucleate within
      the polymer nanofibers and subsequently catalyze graphitization of the
      surrounding polymer matrix and following oxidation, create an interconnected
      graphite-metal oxide framework with large pore channels, considerable active
      sites, and high specific surface area. The metal/metal oxide@N-doped graphitic
      carbon fibers, especially Co3 O4 , exhibit comparable ORR catalytic activity but
      superior stability and methanol tolerance versus Pt in alkaline solutions, which
      can be ascribed to the synergistic chemical coupling effects between Co3 O4 and
      robust 1D porous structures composed of interconnected N-doped graphitic
      nanocarbon rings. This finding provides a novel insight into the design of
      functional electrocatalysts using electrospun carbon nanomaterials for their
      application in energy storage and conversion fields.

PMID- 29356315
TI  - Utility values for childhood obesity interventions: a systematic review and meta
      analysis of the evidence for use in economic evaluation.
AB  - Rigorous estimates of preference-based utilities are important inputs into
      economic evaluations of childhood obesity interventions, yet no published review
      currently exists examining utility by weight status in paediatric populations. A
      comprehensive systematic literature review and meta-analysis was therefore
      undertaken, pooling data on preference-based health state utilities by weight
      status in children using a random-effects model. Tests for heterogeneity were
      performed, and publication bias was assessed. Of 3,434 potentially relevant
      studies identified, 11 met our eligibility criteria. Estimates of Cohen's d
      statistic suggested a small effect of weight status on preference-based
      utilities. Mean utility values were estimated as 0.85 (95% uncertainty interval
      [UI] 0.84-0.87), 0.83 (95% UI 0.81-0.85), 0.82 (95% UI 0.79-0.84) and 0.83 (95%
      UI 0.80-0.86) for healthy weight, overweight, obese and overweight/obese states,
      respectively. Meta-analysis of studies reporting utility values for both healthy
      weight and overweight/obese participants found a statistically significant
      weighted mean difference (0.015, 95% UI 0.003-0.026). A small but statistically
      significant difference was also estimated between healthy weight and overweight
      participants (0.011, 95% UI 0.004-0.018). Study findings suggest that paediatric
      specific benefits of obesity interventions may not be well reflected by available
      utility measures, potentially underestimating cost-effectiveness if weight loss
      in childhood/adolescence improves health or well-being.

PMID- 29356314
TI  - Plasma metabolome analysis of patients with major depressive disorder.
AB  - AIM: This study sought to characterize the plasma metabolite profiling of
      patients with major depressive disorder (MDD). METHODS: Psychiatric assessments
      were made with the Structured Clinical Interview for DSM-IV Axis I Disorders. In
      the exploratory cohort, plasma metabolite profiles of 34 MDD patients and 31
      mentally healthy controls were compared using capillary electrophoresis-mass
      spectrometry. Among the candidate metabolites, we focused on a metabolite showing
      the largest difference. The absolute concentrations were measured in two cohorts
      from a psychiatric primary care clinic to characterize the accuracy of the
      metabolite biomarker. RESULTS: Among 23 metabolites significantly lower in the
      MDD group than in healthy controls, we focused on phosphoethanolamine (PEA) as a
      candidate. The reduction of PEA levels in MDD was checked in independent clinical
      sample sets. An ion-chromatography-fluorescence detection method was developed to
      measure plasma PEA levels. In the preliminary cohort, we examined 34 MDD and 43
      non-MDD subjects. The area under the receiver-operator curve (AUC) was 0.92, with
      sensitivity/specificity greater than 88%, at a cut-off of 1.46 MUM. In the
      checking cohort, with 10 MDD and 13 non-MDD subjects, AUC was 0.89, with
      sensitivity/specificity of 86% and 100%, respectively, at a cut-off of 1.48 MUM.
      Plasma PEA inversely correlated with MDD severity, depressed mood, loss of
      interest, and psychomotor retardation. CONCLUSION: These results suggest that
      plasma PEA level could be a candidate biomarker of MDD in the clinical setting.
      Further studies comparing MDD and mentally healthy controls are needed to confirm
      the utility of PEA as a biomarker for depression.

PMID- 29356316
TI  - Effects of iron and vitamin B12 deficiencies on peripheral blood colony-forming
      unit capacity.
AB  - Iron and vitamin B12 deficiencies are two of the most common diseases in the
      childhood group. Deficiencies of iron and vitamin B12 affect many systems in the
      body. In this study, to discover the effects of iron and vitamin B12 deficiencies
      on the hematopoietic stem cells, we studied CFU assay from peripheral blood. One
      hundred and two children were included in our study and were evaluated in five
      categories: iron deficiency, iron deficiency anemia, vitamin B12 deficiency, iron
      and vitamin B12 deficiency, and controls. As a result of statistical analysis, no
      significant difference was detected between five groups in terms of CFU assays.
      The results of our study suggest that, in emergent situations, stem cell samples
      can be collected before treatment with B12 or iron which are common deficiencies
      in donors of hematopoietic stem cell transplantation. We conclude that we could
      reach more accurate results by designing a study which contains more patients and
      includes in vivo results.

PMID- 29356317
TI  - The use of vascular homografts in pediatric small bowel transplantation: Single
      center experience over a decade.
AB  - Intestinal transplantation in children has evolved with more isolated small
      intestine transplants being performed compared to combined liver-intestine
      transplants. Consequently, surgical techniques have changed, frequently requiring
      the use of vascular homografts of small caliber to revascularize the isolated
      small intestine, the impact of which on outcomes is unknown. Among 106 pediatric
      intestine and multivisceral transplants performed at our center since 2003, 33
      recipients of an isolated small intestine graft were included in this study.
      Outcome parameters were thrombotic complications, graft, and patient survival. A
      total of 29 of 33 (87.9%) patients required arterial and/or venous homografts
      from the same donor, mainly iliac or carotid artery and iliac or innominate vein,
      respectively (donor's median age 1.1 years [2 months to 23 years], median weight
      10 kg [14.7-48.5]). Post-transplant, there were three acute arterial homograft
      thromboses and one venous thrombosis resulting in two peri-operative graft
      salvages and two graft losses. Three of four thromboses occurred in patients with
      primary hypercoagulable state, including the two graft losses. Overall, at a
      median of 4.1 years (1-10.2) from transplant, 29 of 33 (88%) patients are alive
      with 26 of 33 (79%) functioning grafts. The procurement of intact, size-matched
      donor vessels and the management of effective post-transplant anticoagulation are
      critical.

PMID- 29356318
TI  - Standardisation of inactivated influenza vaccines-Learning from history.
AB  - The single radial immunodiffusion assay has been the accepted method for
      determining the potency of inactivated influenza vaccines since 1978. The
      worldwide adoption of this assay for vaccine standardisation was facilitated
      through collaborative studies that demonstrated a high level of reproducibility
      and its applicability to the different types of influenza vaccine being produced
      at that time. Clinical evidence indicated the relevance of SRID as a potency
      assay. Unique features of the SRID assay are likely responsible for its longevity
      even as newer technologies for vaccine characterisation have been developed and
      refined. Nevertheless, there are significant limitations to the SRID assay that
      indicate the need for improvement, and there has been a substantial amount of
      work undertaken in recent years to develop and evaluate alternative potency
      assays, including collaborative studies involving research laboratories,
      regulatory agencies and vaccine manufacturers. Here, we provide an overview of
      the history of inactivated influenza vaccine potency testing, the current state
      of alternative assay development and the some of the major challenges to be
      overcome before implementation of new assays for potency determination.

PMID- 29356319
TI  - Comments on a new classification, treatment algorithm and prognosis-estimating
      system for sigmoid volvulus: the role of percutaneous endoscopic colostomy.

PMID- 29356320
TI  - Deconvolution models for a better understanding of natural microbial communities
      enumerated by flow-cytometry.

PMID- 29356321
TI  - Toward a mechanistic explanation of phenotypic evolution: The need for a theory
      of theory integration.
AB  - Reconciling different underlying ontologies and explanatory contexts has been one
      of the main challenges and impediments for theory integration in biology. Here,
      we analyze the challenge of developing an inclusive and integrative theory of
      phenotypic evolution as an example for the broader challenge of developing a
      theory of theory integration within the life sciences and suggest a number of
      necessary formal steps toward the resolution of often incompatible (hidden)
      assumptions. Theory integration in biology requires a better formal understanding
      of the structure of biological theories The strategy for integrating theories
      crucially depends on the relationships of the underlying ontologies.

PMID- 29356322
TI  - Synthesis and characterization of biogenic selenium nanoparticles with
      antimicrobial properties made by Staphylococcus aureus, methicillin-resistant
      Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa.
AB  - Antimicrobial resistance is a global concern that affects more than two million
      people each year. Therefore, new approaches to kill bacteria are needed. One of
      the most promising methodologies may come from metallic nanoparticles, since
      bacteria may not develop a resistance to these nanostructures as they do for
      antibiotics. While metallic nanoparticle synthesis methods have been well
      studied, they are often accompanied by significant drawbacks such as cost,
      extreme processing conditions, and toxic waste production since they use harsh
      chemicals such as corrosive agents (hydrazine) or strong acids (hydrochloride
      acid). In this work, we explored the environmentally safe synthesis of selenium
      nanoparticles, which have shown promise in killing bacteria. Using Escherichia
      coli, Pseudomonas aeruginosa, Methicillin-resistance Staphylococcus aureus, and
      S. aureus, 90-150 nm average diameter selenium nanoparticles were synthesized
      using an environmentally safe approach. Nanoparticles were characterized using
      transmission electron microscopy, energy dispersive X-ray spectroscopy to
      determine the chemical composition, and inductively coupled plasma mass
      spectrometry to validate chemistry. Nanoparticles were also characterized and
      tested for their ability to inhibit bacterial growth. A decay in bacterial growth
      after 24 h was achieved against both S. aureus and E. coli at biogenic selenium
      nanoparticle concentrations from 25 to 250 ug/mL and showed no significant
      cytotoxicity effect against human dermal fibroblasts for 24 h. Bacteria were able
      to synthesize selenium nanoparticles through the use of different functional
      structures within the organisms, mainly enzymes such as selenite reductases.
      Therefore, biogenic selenium nanoparticles made by bacteria represent a viable
      approach to reduce bacteria growth without antibiotics overcoming the drawbacks
      of synthetic methods that employ toxic chemicals. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1400-1412, 2018.

PMID- 29356323
TI  - Layered Aggregation with Steric Effect: Morphology-Homogeneous Semiconductor MoS2
      as an Alternative 2D Probe for Visual Immunoassay.
AB  - Liquid-phase exfoliation routes unavoidably generate 2D nanostructures with
      inhomogeneous morphologies. Herein, thickness-dependent sorting of exfoliated
      nanostructures is achieved via a treatment of differential-zone centrifugation in
      the surfactant aqueous phase. With this approach, homogeneous MoS2 nanosheets are
      obtained, and due to the intrinsic semiconducting characteristics, those 2D
      nanosheets are endowed with desired optical properties, rivaling classic gold
      nanoparticles in sensing applications. Furthermore, MoS2 nanosheets with high
      uniformity and chemical inertness are coupled with proteins, exhibiting high
      performance in stability and anti-interferences for bioanalysis. As a consequence
      of aggregation-induced steric effect, distinguishing running shifts of antibody
      anchored conjugates in gel electrophoresis are visually responsive to those
      specific antigens. This assay enables the easy and fast monitoring of tumor
      biomarkers just according to "naked-eye" identification of band location in
      electrophoresis results, which are presented by an alternative visual probe of 2D
      MoS2 -protein conjugates. The developed visual immunoassay with the synergistic
      effect of gel electrophoresis techniques and 2D semiconductors pushes significant
      progress in "home-made" tests for disease early diagnosis.

PMID- 29356324
TI  - Kinetic Analysis and Structural Interpretation of Competitive Ligand Binding for
      NO Dioxygenation in Truncated Hemoglobin N.
AB  - The conversion of nitric oxide (NO) into nitrate (NO3- ) by dioxygenation
      protects cells from lethal NO. Starting from NO-bound heme, the first step in
      converting NO into benign NO3- is the ligand exchange reaction FeNO+O2 ->FeO2
      +NO, which is still poorly understood at a molecular level. For wild-type (WT)
      truncated hemoglobin N (trHbN) and its Y33A mutant, the calculated barriers for
      the exchange reaction differ by 1.5 kcal mol-1 , compared with 1.7 kcal mol-1
      from experiment. It is directly confirmed that the ligand exchange reaction is
      rate-limiting in trHbN and that entropic contributions account for 75 % of the
      difference between the WT and the mutant. Residues Tyr 33, Phe 46, Val 80, His
      81, and Gln 82 surrounding the active site are expected to control the reaction
      path. By comparison with electronic structure calculations, the transition state
      separating the two ligand-bound states was assigned to a 2 A state.

PMID- 29356325
TI  - Five New Alkaloids from the Roots of Sophora flavescens.
AB  - Five new quinolizidine alkaloids, including three sparteine-type alkaloids (1 -
      3) and two cytisine-type alkaloids (4 and 5), along with four known ones, were
      isolated from the roots of Sophora flavescens. Their structures were determined
      by extensive spectroscopic techniques including IR, UV, NMR, and HR-ESI-MS. All
      the compounds were evaluated for their antibacterial activities against
      Staphylococcus aureus and Escherichia coli.

PMID- 29356326
TI  - Six New Polyhydroxysteroidal Glycosides, Anthenosides S1 - S6, from the Starfish
      Anthenea sibogae.
AB  - Six new polyhydroxysteroidal glycosides, anthenosides S1  - S6 (1 - 6), along
      with a mixture of two previously known related glycosides, 7 and 8, were isolated
      from the methanolic extract of the starfish Anthenea sibogae. The structures of 1
      - 6 were established by NMR and HR-ESI-MS techniques as well as by chemical
      transformations. All new compounds have a 5alpha-cholest-8(14)-ene
      3alpha,6beta,7beta,16alpha-tetrahydroxysteroidal nucleus and differ from majority
      of starfish glycosides in positions of carbohydrate moieties at C(7) and C(16) (1
      - 4, 6) or only at C(16) (5). The 4-O-methyl-beta-d-glucopyranose residue (2) and
      Delta24 -cholestane side chain (3) have not been found earlier in the starfish
      steroidal glycosides. The mixture of 7 and 8 slightly inhibited the proliferation
      of human breast cancer T-47D cells and decreased the colony size in the colony
      formation assay.

PMID- 29356328
TI  - Confined Self-Assembly in Two-Dimensional Interlayer Space: Monolayered
      Mesoporous Carbon Nanosheets with In-Plane Orderly Arranged Mesopores and a
      Highly Graphitized Framework.
AB  - Although two-dimensional (2D) carbon materials are widely investigated, a well
      defined 2D carbon nanosheet with an ordered mesostructure has rarely been
      realized. Monolayer-ordered mesoporous carbon nanosheets (OMCNS) were prepared
      through confinement assembly of resol and F127 in the interlayer of
      montmorillonite (MONT). The nanoscale distance of the interlayer space of MONT
      only allow the assembly of resol and F127 in the same plane, leading to ordered
      mesopores perpendicular to carbon nanosheets, and favor the formation of sp2
      carbon, resulting in a high degree of graphitization. The mesopores on the carbon
      nanosheets provide efficient ion diffusion, and the high degree of graphitization
      provides a fast electron-transport route, enabling OMCNS as excellent electrode
      materials for electric double layer capacitors.

PMID- 29356329
TI  - Incorporation of bacteriophages in polycaprolactone/collagen fibers for
      antibacterial hemostatic dual-function.
AB  - Effective and affordable, antibacterial and hemostatic materials are of great
      interests in clinical wound care practices. Herein, Enterobacteria phage T4 were
      incorporated in polycaprolactone/collagen I (PCL-ColI) nanofibers via
      electrospinning in order to eradicate Escherichia coli infection and meanwhile
      establish hemostasis. Tensile strength of the membrane was significantly enhanced
      with increased PCL ratio. Those with a collagen component above 70% were
      demonstrated to be more hemostatic with shorter hemostatic time and smaller
      amount of bleeding. On the other hand, the T4 phage incorporated PCL-ColI
      membrane (PCL:ColI = 30%/70%, w/w) exhibited the optimal antibacterial efficiency
      (above 90%). The in vivo evaluation indicated that the PCL-ColI B (30%:70%, w/w)
      membrane fully degraded in 8 weeks and no obvious pathological reaction to muscle
      and subcutaneous layer tissues in the back of rabbit was found. The novel fibrous
      hemostatic materials coupled with phage therapy hold great promise in designing
      novel antibacterial, hemostatic wound dressings that addresses concerns of
      antibiotic resistance. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater, 106B: 2588-2595, 2018.

PMID- 29356327
TI  - Functions of autophagy in the tumor microenvironment and cancer metastasis.
AB  - Macro-autophagy is an ancient and highly conserved self-degradative process that
      plays a homeostatic role in normal cells by eliminating organelles, pathogens,
      and protein aggregates. Autophagy, as it is routinely referred to, also allows
      cells to maintain metabolic sufficiency and survive under conditions of nutrient
      stress by recycling the by-products of autophagic degradation, such as fatty
      acids, amino acids, and nucleotides. Tumor cells are more reliant than normal
      cells on autophagy for survival in part due to their rapid growth rate, altered
      metabolism, and nutrient-deprived growth environment. How this dependence of
      tumor cells on autophagy affects their progression to malignancy and metastatic
      disease is an area of increasing research focus. Here, we review recent work
      identifying critical functions for autophagy in tumor cell migration and
      invasion, tumor stem cell maintenance and therapy resistance, and cross-talk
      between tumor cells and their microenvironment.

PMID- 29356330
TI  - The Controversial Orientation of Adenine on Gold and Silver.
AB  - In which orientation does adenine adsorb on gold and silver surfaces? This
      question has been a matter of debate for over 30 years. Since the dawn of surface
      enhanced Raman spectroscopy (SERS); it and other techniques such as tip-enhanced
      Raman spectroscopy (TERS), surface-enhanced infrared absorption spectroscopy
      (SEIRAS), scanning tunneling microscopy (STM), density functional theory (DFT)
      simulations, and more, have been used in many attempts to answer this seemingly
      straightforward, yet controversial, question. Herein, the timeline and recent
      advances on this topic are explored, and the frequently contradictory findings
      are put into context and discussed.

PMID- 29356331
TI  - Design of Metal-Free Polymer Carbon Dots: A New Class of Room-Temperature
      Phosphorescent Materials.
AB  - Polymer carbon dots (PCDs) are proposed as a new class of room-temperature
      phosphorescence (RTP) materials. The abundant energy levels in PCDs increase the
      probability of intersystem crossing (ISC) and their covalently crosslinked
      framework structures greatly suppress the nonradiative transitions. The efficient
      methods allow the manufacture of PCDs with unique RTP properties in air without
      additional metal complexation or complicated matrix composition. They thus
      provide a route towards the rational design of metal-free RTP materials that may
      be synthesized easily. Furthermore, we find that RTP is associated with a
      crosslink-enhanced emission (CEE) effect, which provides further routes to design
      improved PCDs with diverse RTP performance. Our results show the potential of
      PCDs as a universal route to achieve effective metal-free RTP.

PMID- 29356332
TI  - Feasibility and preliminary efficacy of a smartphone application intervention for
      subthreshold depression.
AB  - AIM: We developed a motion picture-reproducing smartphone application (app)
      designed to improve self-confidence in individuals with subthreshold depression
      (StD) and examined the feasibility and preliminary efficacy of an app
      intervention for individuals with StD. METHODS: We conducted an open-label,
      single-arm pre-post study of 22 young adults with StD. Our intervention involved
      app usage for at least 70 min/wk for 5 weeks. The primary outcome measure was the
      adherence rate. Secondary outcome measures were safety and Center for
      Epidemiologic Studies Depression Scale (CES-D) scores. RESULTS: No participants
      dropped out during the study. The adherence rate was 50%. The mean time of app
      use over 5 weeks was 124.23 +/- 81.94 min/wk. No adverse events were reported.
      The CES-D scores were significantly improved at 5 weeks post-intervention.
      CONCLUSIONS: Although this app intervention has the potential to reduce
      depressive symptoms, the app needs to be improved to increase adherence rates.

PMID- 29356333
TI  - Limitations of Vaginal Birth After Cesarean Success Prediction.
AB  - The Society for Maternal-Fetal Medicine endorses an algorithm for estimating the
      probability of successful vaginal birth for women undergoing trial of labor after
      cesarean (TOLAC). The algorithm is available online in the form of an easy-to-use
      calculator. This calculator has significant limitations that are easily
      overlooked by women and providers alike. The calculator has much greater positive
      than negative predictive power, and it cannot predict unsuccessful TOLAC or
      uterine rupture. Furthermore, the calculator cannot predict rare catastrophes,
      such as unplanned hysterectomy, permanent injury, or death. Predictions are
      heavily influenced by race and ethnicity, which are social and not biological
      constructs. Relevant variables, such as provider attitudes and institutional
      differences, are not accounted for. Providers should be mindful and transparent
      about calculator limitations when counseling women, particularly Latina and
      African American women. It may be appropriate to use the calculator to inform but
      not restrict women's options.

PMID- 29356334
TI  - OMIP-044: 28-color immunophenotyping of the human dendritic cell compartment.
AB  - This work describes the first 30-parameter immunophenotyping of the human
      dendritic cell (DC) compartment using fluorescent-based flow cytometry. The
      optimized panel allows for simultaneous detection of 21 myeloid-centric markers
      distinguishing all canonical DC subsets, with parallel enumeration of monocytes,
      T and B cells as well as NK cells. Thus, this panel will be useful for extensive
      phenotyping of immune cells from a variety of human samples limited in size.

PMID- 29356335
TI  - Pediatric patient with end-stage kidney disease secondary to Eagle-Barrett
      syndrome and metastatic unresectable hepatoblastoma treated successfully with
      chemotherapy and liver-kidney transplant.
AB  - HBL is the most common malignant liver neoplasm in children. The etiology of HBL
      is largely unknown but there are certain syndromes, such as Beckwith-Wiedemann
      syndrome, that have been clearly associated with an increased incidence of this
      malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly
      characterized by lax abdominal musculature, bilateral cryptorchidism requiring,
      in some cases, hemodialysis due to significant kidney and urinary tract
      dysfunctions. Despite an improvement on the survival rates of patients with
      advanced-stage HBL, the presence of concomitant end-stage renal disease that
      occurs in patients with EBS constitutes a therapeutic challenge for the clinician
      not only due to the use of nephrotoxic chemotherapy but also due to the potential
      need for multi-organ transplant. We report case of a 2-year-old male patient with
      EBS diagnosed with stage IV, metastatic HBL successfully treated with multi-agent
      chemotherapy while on dialysis whom then underwent a simultaneous liver-kidney
      transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved
      cancer remission with normalization of his renal function. Our report emphasizes
      that patients with HBL in the setting of EBS will not only require careful kidney
      function monitoring while receiving chemotherapy, but they might also need to
      undergo multi-organ transplantation in order to achieve adequate cancer control
      and also normalization of their kidney function. Awareness of this unusual
      association calls for further investigation to potentially establish a genetic
      association between these two disease processes.

PMID- 29356336
TI  - Exploring Approximate Bayesian Computation for inferring recent demographic
      history with genomic markers in nonmodel species.
AB  - Approximate Bayesian computation (ABC) is widely used to infer demographic
      history of populations and species using DNA markers. Genomic markers can now be
      developed for nonmodel species using reduced representation library (RRL)
      sequencing methods that select a fraction of the genome using targeted sequence
      capture or restriction enzymes (genotyping-by-sequencing, GBS). We explored the
      influence of marker number and length, knowledge of gametic phase, and tradeoffs
      between sample size and sequencing depth on the quality of demographic inferences
      performed with ABC. We focused on two-population models of recent spatial
      expansion with varying numbers of unknown parameters. Performing ABC on simulated
      data sets with known parameter values, we found that the timing of a recent
      spatial expansion event could be precisely estimated in a three-parameter model.
      Taking into account uncertainty in parameters such as initial population size and
      migration rate collectively decreased the precision of inferences dramatically.
      Phasing haplotypes did not improve results, regardless of sequence length.
      Numerous short sequences were as valuable as fewer, longer sequences, and
      performed best when a large sample size was sequenced at low individual depth,
      even when sequencing errors were added. ABC results were similar to results
      obtained with an alternative method based on the site frequency spectrum (SFS)
      when performed with unphased GBS-type markers. We conclude that unphased GBS-type
      data sets can be sufficient to precisely infer simple demographic models, and
      discuss possible improvements for the use of ABC with genomic data.

PMID- 29356337
TI  - Self-organized Ruthenium-Barium Core-Shell Nanoparticles on a Mesoporous Calcium
      Amide Matrix for Efficient Low-Temperature Ammonia Synthesis.
AB  - A low-temperature ammonia synthesis process is required for on-site synthesis.
      Barium-doped calcium amide (Ba-Ca(NH2 )2 ) enhances the efficacy of ammonia
      synthesis mediated by Ru and Co by 2 orders of magnitude more than that of a
      conventional Ru catalyst at temperatures below 300  degrees C. Furthermore, the
      presented catalysts are superior to the wustite-based Fe catalyst, which is known
      as a highly active industrial catalyst at low temperatures and pressures.
      Nanosized Ru-Ba core-shell structures are self-organized on the Ba-Ca(NH2 )2
      support during H2 pretreatment, and the support material is simultaneously
      converted into a mesoporous structure with a high surface area (>100 m2  g-1 ).
      These self-organized nanostructures account for the high catalytic performance in
      low-temperature ammonia synthesis.

PMID- 29356338
TI  - In utero exposure to the 1918 pandemic influenza in Denmark and risk of dementia.
AB  - BACKGROUND: Substantial but inconclusive evidence suggests in utero exposure to
      influenza infection may be linked with Alzheimer's disease. OBJECTIVES: We
      examined whether individuals exposed in utero to the 1918 influenza pandemic are
      at increased risk of dementia. PATIENTS/METHODS: In this cohort study,
      surveillance data were used to identify months when influenza activity was at its
      peak during the pandemic. Using birth dates, exposed and unexposed individuals
      were identified based on whether they were in utero during >=1 of the peak
      months. The outcome, any type of dementia, was identified in population-based
      medical registries. Time and age at risk were restricted so exposed and unexposed
      had equal time at risk; diagnoses for dementia were assessed between ages 62 and
      92, with a maximum of 30 years at risk. Poisson regression was used to estimate
      sex-adjusted incidence rate ratios (IRRs). RESULTS: We identified 106 479 exposed
      and 177 918 unexposed persons. Using the cumulative risk function, there were
      similar proportions of exposed and unexposed with a dementia diagnosis at 11.9%
      and 11.7%, respectively. Across all ages, the IRR for the association between in
      utero influenza exposure and any dementia was 1.01 (95% CI 0.99-1.04); for
      Alzheimer's disease, it was 0.97 (0.93-1.01). When stratified by age and sex, and
      when dementia type was examined, estimates of association were also null or close
      to null. CONCLUSIONS: Our study suggests there is likely not an association
      between in utero exposure to the 1918 influenza pandemic and dementia among those
      62 and older.

PMID- 29356339
TI  - Caregiver active participation in psychoeducational intervention improved
      caregiving skills and competency.
AB  - AIM: To determine whether giving dementia caregivers active psychoeducational
      intervention is more efficacious than passive intervention for improving their
      caregiving skills and reducing their caregiving burden. METHODS: This study was a
      prospective, single-blinded, controlled trial with 43 caregiver/person-with
      dementia dyads. The dyads were randomly assigned to the active psychoeducational
      intervention (AP) group, which used role-play, discussion, and development of
      problem-solving capacity to build up their caregiving skills and competence, or
      the passive psychoeducational intervention (PP) group, which gave caregivers
      educational materials on common caregiving strategies. Primary outcomes were the
      levels of caregiver competence (Care Skill Inventory [CSI]), burden (Chinese
      Zarit Burden Inventory [CZBI]), and distress caused by the behavioral and
      psychological symptoms of dementia (Neuropsychiatric Inventory-Questionnaire [NPI
      Q]). Outcomes were assessed pre-test, post-test and after 3 months. Repeated
      measures one-way analysis of variance was used to compare mean-change scores
      between time-points, and generalized estimating equations (GEE) were used to
      compare groups. RESULTS: Post-test or 3-month (or both) Care Skill Inventory,
      Chinese Zarit Burden Inventory and Neuropsychiatric Inventory-Questionnaire
      distress levels were significantly (p < 0.05) better in the AP but not in the PP
      group. The generalized estimating equation intergroup comparison, adjusted for
      potential confounders, showed that Care Skill Inventory in the AP group was more
      significantly improved than in the PP group, and that Chinese Zarit Burden
      Inventory nearly reached significance. CONCLUSIONS: Active rather than passive
      psychoeducation, even in a short (3 months) intervention of six visits, was more
      efficacious for improving caregiving competence. Future studies will require
      larger samples. Geriatr Gerontol Int 2018; 18: 750-757.

PMID- 29356340
TI  - Overweight or underweight and the risk of decline in activities of daily living
      in a 22-year cohort study of a Japanese sample.
AB  - AIM: The present study aimed to clarify the association between body mass index
      (BMI) and the activities of daily living (ADL). Although BMI is likely to be
      concerned regarding the relationship with specific diseases or mortality, few
      studies have focused on the relationship of BMI and ADL. METHODS: A total of 3353
      Japanese participants of a 22-year cohort study from 1990 to 2012 aged 45-74
      years at baseline were divided into four groups according to their BMI levels:
      <=18.5, 18.5-21.9 (reference), 22.0-24.9 and >=25.0 kg/m2 . Outcomes were
      becoming dependent in ADL (including death after ADL decline) and death without
      observation of ADL decline as a competing risk. Sex-specific multinomial logistic
      regression analysis was carried out in 2017 to estimate the odds ratios (OR)
      after adjusting for age, smoking, alcohol drinking, hypertension,
      hypercholesterolemia, diabetes and serum albumin. RESULTS: After multivariable
      adjustment, though the relationship between BMI and risk of ADL decline was U
      shaped among women, only those with BMI >=25.0 showed a higher risk for ADL
      decline (OR 1.39, 95% CI 1.01-1.92) compared with the reference. The OR for death
      without observation of ADL decline was significantly lower for men with BMI
      >=25.0 (OR 0.70, 95% CI 0.50-0.98). CONCLUSIONS: This study suggests being
      overweight is a good predictor of future decline in ADL for women, whereas men
      with BMI 22.0-24.9 had lower risks of ADL decline. Appropriate management of
      weight in older women could prevent disabilities. Geriatr Gerontol Int 2018; 18:
      799-805.

PMID- 29356341
TI  - Cryopreserved neonatal hepatocytes may be a source for transplantation:
      Evaluation of functionality toward clinical use.
AB  - Neonatal livers are a potential source of good-quality hepatocytes for clinical
      transplantation. We compared viability and function of neonatal hepatocytes (NHs)
      and adult hepatocytes (AHs) and report their clinical use both intraportally and
      in alginate microbeads. Following isolation from donor livers, hepatocyte
      function was assessed using albumin, alpha-1-antitrypsin, and factor VII.
      Metabolic function was investigated by measuring resorufin conjugation, ammonia
      metabolism, uridine diphosphate glucuronosyltransferase enzyme activity, and
      cytochrome P450 (CYP) function following induction. Activation of the instant
      blood-mediated inflammatory reaction by NHs and AHs was investigated using an in
      vitro blood perfusion model, and tissue factor expression was analyzed using real
      time polymerase chain reaction (RT-PCR). Clinical hepatocyte transplantation (HT)
      was undertaken using standard protocols. Hepatocytes were isolated from 14
      neonatal livers, with an average viability of 89.4% +/- 1.8% (mean +/- standard
      error of the mean) and average yield of 9.3 * 106 +/- 2.0 * 106 cells/g.
      Hepatocytes were isolated from 14 adult livers with an average viability of 78.6%
      +/- 2.4% and yield 2.2 * 106 +/- 0.5 * 105 cells/g. NHs had significantly higher
      viability after cryopreservation than AHs, with better attachment efficiency and
      less plasma membrane leakage. There were no differences in albumin, alpha-1
      antitrypsin, and factor VII synthesis between NHs and AHs (P > 0.05). Neonatal
      cells had inducible phase 1 enzymes as assessed by CYP function and functional
      phase 2 enzymes, in which activity was comparable to AHs. In an in vitro blood
      perfusion model, AHs elicited increased thrombus formation with a greater
      consumption of platelets and white cells compared with NHs (28.3 * 109 versus
      118.7 * 109 and 3.3 * 109 versus 6.6 * 109 ; P < 0.01). Intraportal
      transplantation and intraperitoneal transplantation of alginate encapsulated
      hepatocytes was safe, and preliminary data suggest the cells may activate the
      immune response to a lesser degree than adult cells. In conclusion, we have shown
      NHs have excellent cell viability, function, and drug metabolism making them a
      suitable alternative source for clinical HT. Liver Transplantation 24 394-406
      2018 AASLD.

PMID- 29356343
TI  - Metataxonomic approach to decipher the polymicrobial burden in diabetic foot
      ulcer and its biofilm mode of infection.
AB  - Chronic diabetic foot is a global burden affecting millions of people, and the
      chronicity of an ulcer is directly linked to the diverse bacterial burden and its
      biofilm mode of infection. The bacterial diversity of 100 chronic diabetic ulcer
      samples was profiled via traditional culturing method as well as metagenomic
      approach by sequencing the 16S rRNA V3 hyper-variable region on Illumina Miseq
      Platform (Illumina, Inc., San Diego, CA). All the relevant clinical metadata,
      including duration of diabetes, grade of ulcer, presence of neuropathy, and
      glycaemic level, were noted and correlated with the microbiota. The occurrence
      and establishment of bacterial biofilm over chronic wound tissues was revealed by
      Fluorescent in situ Hybridization and Scanning Electron Microscopy. The biofilm
      forming ability of predominant bacterial isolates was studied via crystal violet
      assay and Confocal Laser Scanning Microscopy. The dominant phyla obtained from
      bacterial diversity analysis were Firmicutes, Proteobacteria, and Actinobacteria.
      The dominant aerobic pathogens identified by culture method are Pseudomonas,
      Proteus, Enterococcus, and Staphylococcus, whereas high-throughput sequencing
      revealed heightened levels of Streptococcus and Corynebacterium along with 22
      different obligate anaerobes. The biofilm occurrence in chronic diabetic ulcer
      infection is well analysed. Herein, we illustrate the comprehensive pattern of
      bacterial infection and identify the community composition of chronic wound
      pathogenic biofilm.

PMID- 29356342
TI  - The Human Eye Proteome Project: Updates on an Emerging Proteome.
AB  - The human eye is a complex organ consisting of multiple compartments with unique
      and specialized properties that reflect their varied functions. Although there
      have been advancements in ocular imaging and therapeutics over the past decade,
      the pathogenesis of many common eye diseases remains poorly understood.
      Proteomics is an invaluable tool to gain insight into pathogenesis, diagnosis,
      and treatment of eye diseases. By 2013, when the Human Eye Proteome Project (also
      known as the EyeOme) was founded, there were 4842 nonredundant proteins
      identified in the human eye. Twenty-three recent papers on the human eye proteome
      were identified in PubMed searches. These papers were used to compile an updated
      resource of 9782 nonredundant proteins in the human eye. This updated catalogue
      sheds light on the molecular makeup of previously undescribed proteomes within
      the human eye, including optic nerve, sclera, iris, and ciliary body, while
      adding additional proteins to previously characterized proteomes such as aqueous
      humor, lens, vitreous, retina, and retinal pigment epithelium/choroid. Although
      considerable advances have been made to characterize the complete proteome of the
      human eye, additional high-quality data are needed to confirm and quantify
      previously discovered eye proteins in both health and disease.

PMID- 29356344
TI  - Fabrication of magnetic zinc adeninate metal-organic frameworks for the
      extraction of benzodiazepines from urine and wastewater.
AB  - In this study, an alternative method for synthesizing magnetic cobalt adeninate
      metal-organic frameworks was developed, and the synthesized materials were
      examined for their potential application for separating and enriching
      benzodiazepines from complex samples. Benzodiazepines, widely used as hypnotics,
      muscle relaxants, sedatives, and anxiolytics, are a class of drugs that require
      accurate detection and monitoring. Results showed that Fe3 O4 nanoparticles could
      be well anchored onto the external surface of cobalt adeninate metal-organic
      frameworks by using amino-silane as a linkage. Their adsorption of
      benzodiazepines was mainly promoted by intermolecular hydrogen binding, pi-pi
      interactions and electrostatic attraction. Their potential application was
      evaluated by extraction of benzodiazepines in urine and wastewater samples prior
      to liquid chromatography with mass spectrometry. Under optimum conditions, the
      calibration curves were linear with a correlation coefficient of >=0.9928 in the
      concentration range of 10-5000 ng/L for lorazepam and 5-5000 ng/L for estazolam,
      chlordiazepoxide, alprazolam, midazolam and triazolam. The limits of detection
      were in the range of 0.71-2.49 ng/L. The percent of extraction recoveries were
      80.2-94.5% for urine and 84.1-94.4% for wastewater, respectively. Results
      suggested that magnetic cobalt adeninate metal-organic frameworks could
      potentially be a promising material for enriching benzodiazepines from urine and
      wastewater with high accuracy and precision.

PMID- 29356345
TI  - Four days of simulated shift work reduces insulin sensitivity in humans.
AB  - AIM: The aim of this study was to investigate the effects of 4 consecutive
      simulated night shifts on glucose homeostasis, mitochondrial function and central
      and peripheral rhythmicities compared with a simulated day shift schedule.
      METHODS: Seventeen healthy adults (8M:9F) matched for sleep, physical activity
      and dietary/fat intake participated in this study (night shift work n = 9; day
      shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4
      nights of shift work were measured by an intravenous glucose tolerance test and a
      hyperinsulinaemic euglycaemic clamp respectively. Muscles biopsies were obtained
      to determine insulin signalling and mitochondrial function. Central and
      peripheral rhythmicities were assessed by measuring salivary melatonin and
      expression of circadian genes from hair samples respectively. RESULTS: Fasting
      plasma glucose increased (4.4 +/- 0.1 vs. 4.6 +/- 0.1 mmol L-1 ; P = .001) and
      insulin sensitivity decreased (25 +/- 7%, P < .05) following the night shift,
      with no changes following the day shift. Night shift work had no effect on
      skeletal muscle protein expression (PGC1alpha, UCP3, TFAM and mitochondria
      Complex II-V) or insulin-stimulated pAkt Ser473, pTBC1D4Ser318 and pTBC1D4Thr642.
      Importantly, the metabolic changes after simulated night shifts occurred despite
      no changes in the timing of melatonin rhythmicity or hair follicle cell clock
      gene expression across the wake period (Per3, Per1, Nr1d1 and Nr1d2). CONCLUSION:
      Only 4 days of simulated night shift work in healthy adults is sufficient to
      reduce insulin sensitivity which would be expected to increase the risk of T2D.

PMID- 29356346
TI  - Predicting the hearing outcome in sudden sensorineural hearing loss via machine
      learning models.
AB  - OBJECTIVE: Sudden sensorineural hearing loss (SSHL) is a multifactorial disorder
      with high heterogeneity, thus the outcomes vary widely. This study aimed to
      develop predictive models based on four machine learning methods for SSHL,
      identifying the best performer for clinical application. DESIGN: Single-centre
      retrospective study. SETTING: Chinese People's liberation army (PLA) hospital,
      Beijing, China. PARTICIPANTS: A total of 1220 in-patient SSHL patients were
      enrolled between June 2008 and December 2015. MAIN OUTCOME MEASURES: An advanced
      deep learning technique, deep belief network (DBN), together with the
      conventional logistic regression (LR), support vector machine (SVM) and
      multilayer perceptron (MLP) were developed to predict the dichotomised hearing
      outcome of SSHL by inputting six feature collections derived from 149 potential
      predictors. Accuracy, precision, recall, F-score and the area under the receiver
      operator characteristic curves (ROC-AUC) were exploited to compare the prediction
      performance of different models. RESULTS: Overall the best predictive ability was
      provided by the DBN model when tested in the raw data set with 149 variables,
      achieving an accuracy of 77.58% and AUC of 0.84. Nevertheless, DBN yielded
      inferior performance after feature pruning. In contrast, the LR, SVM and MLP
      models demonstrated opposite trend as the greatest individual prediction powers
      were obtained when included merely three variables, with the ROC-AUC ranging from
      0.79 to 0.81, and then decreased with the increasing size of input features
      combinations. CONCLUSIONS: With the input of enough features, DBN can be a robust
      prediction tool for SSHL. But LR is more practical for early prediction in
      routine clinical application using three readily available variables, that is
      time elapse between symptom onset and study entry, initial hearing level and
      audiogram.

PMID- 29356347
TI  - Measuring exclusive breastfeeding social support: Scale development and
      validation in Uganda.
AB  - The World Health Organization recommends exclusive breastfeeding (EBF) for 6
      months and continued breastfeeding for at least 2 years. Social support has been
      widely recognized to influence breastfeeding practices. However, existing scales
      do not measure exclusive breastfeeding social support (EBFSS), rather they assess
      social support for any breastfeeding. Further, they are tailored towards high
      income settings. Therefore, our objectives were to develop and validate a tool to
      measure EBFSS in low-income settings. To develop the scale, local and
      international breastfeeding experts were consulted on modifications to the
      Hughes' Breastfeeding Social Support Scale. It was then implemented in an
      observational cohort in Gulu, Uganda, at 1 (n = 238) and 3 (n = 237) months post
      partum (NCT02925429). We performed polychoric and polyserial correlations to
      remove redundant items and exploratory factor analysis at 1 month post-partum to
      determine the latent factor structure of EBFSS. We further applied confirmatory
      factor analysis to assess dimensionality of the scale at 3 months post-partum. We
      then conducted tests of predictive, convergent, and discriminant validity against
      EBF, self-efficacy, general social support, and depression. The modification of
      the Hughes' scale resulted in 18 items, which were reduced to 16 after examining
      variances and factor loadings. Three dimensions of support emerged: Instrumental,
      Emotional, and Informational, with alpha coefficients of 0.79, 0.85, and 0.83,
      respectively. Predictive, convergent, and discriminant validity of the resultant
      EBFSS scale was supported. The EBFSS scale is valid and reliable for measuring
      EBFSS in northern Uganda and may be of use in other low-income settings to assess
      determinants of EBF.

PMID- 29356348
TI  - Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo
      oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore
      Longitudinal Study of Aging.
AB  - Mitochondrial function in human skeletal muscle declines with age. Most evidence
      for this decline comes from studies that assessed mitochondrial function
      indirectly, and the impact of such deterioration with respect to physical
      function has not been clearly delineated. We hypothesized that mitochondrial
      respiration in permeabilized human muscle fibers declines with age and correlates
      with phosphocreatine postexercise recovery rate (kPCr), muscle performance, and
      aerobic fitness. Mitochondrial respiration was assessed by high-resolution
      respirometry in saponin-permeabilized fibers from vastus lateralis muscle
      biopsies of 38 participants from the Baltimore Longitudinal Study of Aging (BLSA;
      21 men, age 24-91 years) who also had available measures of peak oxygen
      consumption (VO2max ) from treadmill tests, gait speed in different tasks, 31 P
      magnetic resonance spectroscopy, isokinetic knee extension, and grip strength.
      Results indicated a significant reduction in mitochondrial respiration with age
      (p < .05) that was independent of other potential confounders. Mitochondrial
      respiratory capacity was also associated with VO2max , muscle strength, kPCr, and
      time to complete a 400-m walk (p < .05). A negative trend toward significance (p
      = .074) was observed between mitochondrial respiration and BMI. Finally,
      transcriptional profiling revealed a reduced mRNA expression of mitochondrial
      gene networks with aging (p < .05). Overall, our findings reinforce the notion
      that mitochondrial function declines with age and may contribute to age
      associated loss of muscle performance and cardiorespiratory fitness.

PMID- 29356349
TI  - Rice copine genes OsBON1 and OsBON3 function as suppressors of broad-spectrum
      disease resistance.
AB  - Breeding for disease resistance is the most effective strategy to control
      diseases, particularly with broad-spectrum disease resistance in many crops.
      However, knowledge on genes and mechanism of broad-spectrum resistance and trade
      off between defence and growth in crops is limited. Here, we show that the rice
      copine genes OsBON1 and OsBON3 are critical suppressors of immunity. Both OsBON1
      and OsBON3 changed their protein subcellular localization upon pathogen
      challenge. Knockdown of OsBON1 and dominant negative mutant of OsBON3 each
      enhanced resistance to rice bacterial and fungal pathogens with either
      hemibiotrophic or necrotrophic lifestyles. The defence activation in OsBON1
      knockdown mutants was associated with reduced growth, both of which were largely
      suppressed under high temperature. In contrast, overexpression of OsBON1 or
      OsBON3 decreased disease resistance and promoted plant growth. However, neither
      OsBON1 nor OsBON3 could rescue the dwarf phenotype of the Arabidopsis BON1
      knockout mutant, suggesting a divergence of the rice and Arabidopsis copine
      genes. Our study therefore shows that the rice copine genes play a negative role
      in regulating disease resistance and their expression level and protein location
      likely have a large impact on the balance between immunity and agronomic traits.

PMID- 29356350
TI  - 1918 pandemic morbidity: The first wave hits the poor, the second wave hits the
      rich.
AB  - BACKGROUND: Whether morbidity from the 1918-19 influenza pandemic discriminated
      by socioeconomic status has remained a subject of debate for 100 years. In lack
      of data to study this issue, the recent literature has hypothesized that
      morbidity was "socially neutral." OBJECTIVES: To study the associations between
      influenza-like illness (ILI) and socioeconomic status (SES), gender, and wave
      during the 1918-19 influenza pandemic. METHODS: Availability of incidence data on
      the 1918-19 pandemic is scarce, in particular for waves other than the "fall
      wave" October-December 1918. Here, an overlooked survey from Bergen, Norway (n =
      10 633), is used to study differences in probabilities of ILI and ILI probability
      ratios by apartment size as a measure of SES and gender for 3 waves including the
      waves prior to and after the "fall wave." RESULTS: Socioeconomic status was
      negatively associated with ILI in the first wave, but positively associated in
      the second wave. At all SES levels, men had the highest ILI in the summer, while
      women had the highest ILI in the fall. There were no SES or gender differences in
      ILI in the winter of 1919. CONCLUSIONS: For the first time, it is documented a
      crossover in the role of socioeconomic status in 1918 pandemic morbidity. The
      poor came down with influenza first, while the rich with less exposure in the
      first wave had the highest morbidity in the second wave. The study suggests that
      the socioeconomically disadvantaged should be prioritized if vaccines are of
      limited availability in a future pandemic.

PMID- 29356351
TI  - How adolescents decide on bariatric surgery: an interpretative phenomenological
      analysis.
AB  - The National Institute of Clinical Excellence states that bariatric surgery may
      be considered for adolescents with severe obesity in 'exceptional circumstances'.
      However, it is not clear what is deemed to be exceptional, and there is a lack of
      long-term outcomes data or research, which would inform patient selection. This
      is an in-depth qualitative study involving five adolescents who had previously
      undergone bariatric surgery (between 1 and 3 years postoperatively) and four who
      were being assessed for the treatment. All patients were from one tertiary NHS
      weight management service offering bariatric surgery to adolescents. Participants
      were interviewed to explore how young people decide whether bariatric surgery is
      an appropriate intervention for them. Of the nine adolescents recruited, four
      were male and five female, aged between 17 and 20 years at the time of interview.
      Participants who had already undergone surgery did so between the ages of 16 and
      18. The data were analysed using interpretative phenomenological analysis, and
      key themes were identified, such as (i) wanting a different future, (ii)
      experiences of uncertainty, (iii) managing the dilemmas and (iv) surgery as the
      last resort. The findings suggest that young people are prepared to accept a
      surgical solution for obesity despite numerous dilemmas. Young people choose this
      intervention as a way of 'normalizing' when they perceive there is nothing better
      available. It is argued that these findings may have implications for the
      counselling of young people living with overweight and obesity and for government
      policy.

PMID- 29356352
TI  - VIIaAT complexes, procoagulant phospholipids, and thrombin generation during
      postprandial lipemia.
AB  - INTRODUCTION: Factor VII activation occurs postprandially. A proportion of
      activated factor VII (VIIa) circulates in complex with antithrombin (VIIaAT). Our
      primary objective was to assess the effects of postprandial lipemia on
      circulating VIIaAT, procoagulant phospholipid (PPL) activity, and thrombin
      generation. METHODS: Plasma samples from postmyocardial infarction patients (n =
      40) and controls (n = 39) were taken before and at 3 and 6 hours during a
      standardized oral fat tolerance test (OFTT). Fasting PPL activity measurements
      were also made in a second cohort of 108 postinfarction patients and 109
      controls. VIIaAT was analyzed with the Asserachrom VIIaAT ELISA, PPL activity
      with the STA-Procoag-PPL kit, and thrombin generation with calibrated automated
      thrombogram with PRP-Reagent as trigger (all Diagnostica Stago products).
      RESULTS: Postprandially, VIIaAT increased in all samples without significant case
      control differences in the overall response during the OFTT. Thrombin generation
      measures peak height and velocity, and PPL activity, were marginally affected by
      the test meal in the controls. Levels of all patient baseline measures were
      significantly different from controls, indicating a more hypercoagulable state,
      and these differences were maintained throughout the OFTT. Fasting samples from
      cases showed higher PPL activity than control samples. CONCLUSION: Viewing VIIaAT
      quantitation as a surrogate for TF activity measurement, postprandial increase in
      VIIaAT may reflect a mechanism that adds to the cardiovascular risk associated
      with postprandial lipemia. On the other hand, the impact of postprandial lipemia
      on PPL activity and thrombin generation seems to be minor.

PMID- 29356354
TI  - Functional Differentiation of Three Pores for Effective Sulfur Confinement in Li
      S Battery.
AB  - Shuttle effect of the dissolved intermediates is regarded as the primary cause
      that leads to fast capacity degradation of Li-S battery. Herein, a microporous
      carbon-coated sulfur composite with novel rambutan shape (R-S@MPC) is synthesized
      from microporous carbon-coated rambutan-like zinc sulfide (R-ZnS@MPC), via an in
      situ oxidation process. The R-ZnS is employed as both template and sulfur
      precursor. The carbon frame of R-S@MPC composite possesses three kinds of pores
      that are distinctly separated from each other in space and are endowed with the
      exclusive functions. The central macropore serves as buffer pool to accommodate
      the dissolved lithium polysulfides (LPSs) and volumetric variation during
      cycling. The marginal straight-through mesoporous, connected with the central
      macropore, takes the responsibility of sulfur storage. The micropores, evenly
      distributed in the outer carbon shell of the as-synthesized R-S@MPC, enable the
      blockage of LPSs. These pores are expected to perform their respective single
      function, and collaborate synergistically to suppress the sulfur loss. Therefore,
      it delivers an outstanding cycling stability, decay rate of 0.013% cycle-1 after
      500 cycles at 1 C, when the sulfur loading is kept at 4 mg cm-2 .

PMID- 29356353
TI  - Effect of the Prevent Alcohol and Risk-Related Trauma in Youth (P.A.R.T.Y.)
      Program among senior school students.
AB  - OBJECTIVE: The Prevent Alcohol and Risk-Related Trauma in Youth (P.A.R.T.Y.)
      Program at The Alfred uses vivid clinical reality to build resilience and prevent
      injury by following a trauma patient's journey through hospital. The present
      study aims to analyse the effect of P.A.R.T.Y. on safety perceptions of driving
      after alcohol, seat belt use and risk-taking activities. METHODS: Pre-programme,
      immediately post-programme and 3-5 months post-programme surveys with questions
      focused on the programme aims were distributed to all consented participants.
      RESULTS: There were 2502 participants during the study period and 1315 (53%)
      responses were received. The mean age was 16.2 (SD 0.8) years, 724 (56%) were
      women and 892 (68%) possessed a learner's permit for driving. Pre-programme, 1130
      (86%) participants reported 'definitely not' likely to drive after drinking
      alcohol, that improved to 1231 (94%) immediately post-programme and 1215 (93%) at
      3-5 months post-programme (P < 0.01). Designating a safe driver after drinking
      was reported by 1275 (97%) pre-programme, 1295 (98%) immediately post-programme
      and 1286 (98.2%) 3-5 months post-programme (P = 0.02). The perception of
      sustaining 'definite' injury after a motor vehicle crash without a seat belt
      increased from 780 (60%) pre-programme to 1051 (80%) immediately post-programme
      and 886 (69%) 3-5 months post-programme (P < 0.01). The possibility of sustaining
      'definite' injury after risk-taking activities was reported by 158 (12%) pre
      programme, 467 (36%) post-programme and 306 (23%) 3-5 months post-programme (P <
      0.01). CONCLUSIONS: The P.A.R.T.Y. Program at The Alfred engaged substantial
      numbers of youths and achieved significant improvements among key outcome
      measures. Objectives were sustained at 3-5 months post-programme, but
      demonstrated decay, highlighting the importance of continual reinforcement.

PMID- 29356355
TI  - Improving Hemocompatibility of Membranes for Extracorporeal Membrane Oxygenators
      by Grafting Nonthrombogenic Polymer Brushes.
AB  - Nonthrombogenic modifications of membranes for extracorporeal membrane
      oxygenators (ECMOs) are of key interest. The absence of hemocompatibility of
      these membranes and the need of anticoagulation of patients result in severe and
      potentially life-threatening complications during ECMO treatment. To address the
      lack of hemocompatibility of the membrane, surface modifications are developed,
      which act as barriers to protein adsorption on the membrane and, in this way,
      prevent activation of the coagulation cascade. The modifications are based on
      nonionic and zwitterionic polymer brushes grafted directly from poly(4-methyl-1
      pentene) (TPX) membranes via single electron transfer-living radical
      polymerization. Notably, this work introduces the first example of well
      controlled surface-initiated radical polymerization of zwitterionic brushes. The
      antifouling layers markedly increase the recalcification time (a proxy of
      initiation of coagulation) compared to bare TPX membranes. Furthermore, platelet
      and leukocyte adhesion is drastically decreased, rendering the ECMO membranes
      hemocompatible.

PMID- 29356356
TI  - Phase angle measured by electrical bioimpedance and global cardiovascular risk in
      older adults.
AB  - AIM: Population aging is a worldwide phenomenon associated with physiological and
      metabolic changes that contribute to the increased prevalence of risk factors for
      cardiovascular disease. The phase angle (PA) is a variable calculated by
      bioelectrical impedance analysis, interpreted as a direct measure of cell
      stability. The objective of the present study was to investigate the correlation
      of PA with the anthropometric measures, metabolic profile and the cardiovascular
      risk estimated by the Global Cardiovascular Risk Score in the elderly population.
      METHODS: A cross-sectional study was carried out with 402 patients aged >60 years
      (70.4 +/- 6.9 years, 74% female) treated in primary care. Patients were evaluated
      by blood pressure, anthropometric measurements and body composition. The score of
      the risk and the stratification of the cardiovascular risk were calculated using
      the criteria from the Framingham Heart Study. RESULTS: Age, systolic blood
      pressure, neck circumference and fat-free mass correlated with PA in female
      patients. In men, age and systolic blood pressure were the variables that
      correlated with the PA in the bivariate analysis. In the multiple linear
      regression, for the female group the risk score presented an independent
      variation with PA (P = 0.051) and age (P < 0.0001). The same correlation was
      observed for the male group both for PA (P = 0.042) and age (P < 0.0001).
      CONCLUSIONS: The present data show an independent association of PA with overall
      cardiovascular risk in the elderly population. Geriatr Gerontol Int 2018; 18: 732
      737.

PMID- 29356357
TI  - CTAPIII/CXCL7: a novel biomarker for early diagnosis of lung cancer.
AB  - It is desirable to have a biomarker which can facilitate low-dose CT in diagnosis
      of early stage lung cancer. CTAPIII/CXCL7 is reported to be a potential biomarker
      for diagnosis of early lung cancer. In this study, we investigated the serum
      level of CTAPIII/CXCL7 in patients at different stage of lung cancer and the
      diagnostic efficacy of CTAPIII/CXCL7 in NSCLC. The plasma level of CTAPIII/CXCL7
      was assayed by ELISA. CEA, SCCAg, and Cyfra211 were measured using a commercial
      chemiluminescent microparticle immunoassay. A total of 419 subjects were
      recruited, including 265 NSCLC patients and 154 healthy individuals. The subjects
      were randomly assigned to a training set and a test set. Receiver operating
      characteristic (ROC) and binary logistic regression analyses were conducted to
      evaluate the diagnostic efficacy and establish diagnostic mathematical model.
      Plasma CTAPIII/CXCL7 levels were significantly higher in NSCLC patients than in
      controls, which was independent of the stage of NSCLC. The diagnostic efficiency
      of CTAPIII/CXCL7 in NSCLC (training set: area under ROC curve (AUC) 0.806, 95%
      CI: 0.748-0.863; test set: AUC 0.773, 95% CI: 0.711-0.835) was greater than that
      of SCCAg, Cyfra21-1, or CEA. The model combining CTAPIII/CXCL7 with CEA, SCCAg,
      and Cyfra21-1 was more effective for NSCLC diagnosis than CTAPIII/CXCL7 alone. In
      addition, plasma level of CTAPIII/CXCL7 may contribute to the early diagnosis of
      NSCLC. CTAPIII/CXCL7 can be used as a plasma biomarker for the diagnosis of
      NSCLCs, particularly early stage lung cancer, with relatively high sensitivity
      and specificity.

PMID- 29356358
TI  - Epigenetics and the maintenance of developmental plasticity: extending the
      signalling theory framework.
AB  - Developmental plasticity, a phenomenon of importance in both evolutionary biology
      and human studies of the developmental origins of health and disease (DOHaD),
      enables organisms to respond to their environment based on previous experience
      without changes to the underlying nucleotide sequence. Although such phenotypic
      responses should theoretically improve an organism's fitness and performance in
      its future environment, this is not always the case. Herein, we first discuss
      epigenetics as an adaptive mechanism of developmental plasticity and use
      signaling theory to provide an evolutionary context for DOHaD phenomena within a
      generation. Next, we utilize signalling theory to identify determinants of
      adaptive developmental plasticity, detect sources of random variability - also
      known as process errors that affect maintenance of an epigenetic signal (DNA
      methylation) over time, and discuss implications of these errors for an
      organism's health and fitness. Finally, we apply life-course epidemiology
      conceptual models to inform study design and analytical strategies that are
      capable of parsing out the potential effects of process errors in the
      relationships among an organism's early environment, DNA methylation, and
      phenotype in a future environment. Ultimately, we hope to foster cross-talk and
      interdisciplinary collaboration between evolutionary biology and DOHaD
      epidemiology, which have historically remained separate despite a shared interest
      in developmental plasticity.

PMID- 29356359
TI  - Impact of body mass index on the oncological outcomes of patients with upper and
      lower urinary tract cancers treated with radical surgery: A multi-institutional
      retrospective study.
AB  - AIM: To evaluate the impact of body mass index (BMI) on the oncological outcomes
      of urothelial carcinoma (UC) patients. PATIENTS AND METHODS: We retrospectively
      analyzed data from 818 patients with upper tract urothelial cancer (UTUC) and
      bladder cancer (BC) who were treated with radical nephroureterectomy (RNU) or
      radical cystectomy (RC) between 1990 and 2015 at six different institutions in
      Japan. Patients with distant metastasis at diagnosis and those who received
      neoadjuvant therapies were excluded, leaving 727 eligible patients (UTUC: n =
      441; BC: n = 286). Patients were classified into four groups according to World
      Health Organization BMI criteria: underweight (BMI <18.5  kg/m2 ), normal weight
      (BMI 18.5-25 kg/m2 ), overweight (BMI 25.1-30 kg/m2 ), and obese (BMI >30 kg/m2
      ). RESULTS: Overweight UTUC and BC patients achieved significantly better cancer
      specific survival (CSS) than the other three groups. However, obese UTUC and BC
      patients had significantly worse CSS than the other three groups (UTUC: P =
      0.031; BC: P = 0.0019). Multivariate analysis of BC patients demonstrated that
      obesity was an independent predictor of unfavorable CSS (hazard ratio [HR] =
      7.47; P = 0.002) and that being underweight was an independent predictor of
      favorable CSS (HR = 0.37; P = 0.029). However, BMI was not a prognostic factor
      for CSS in UTUC patients according to multivariate analysis. CONCLUSIONS: Obesity
      was an independent predictor of BC patients requiring RC. Conversely, being
      underweight was associated with a favorable prognosis for BC patients. However,
      BMI was not an independent prognostic factor in patients with upper urinary tract
      cancer.

PMID- 29356360
TI  - Uranyl tris nitrato as a luminescent probe for trace water detection in
      acetonitrile.
AB  - Uranyl tris nitrato i.e. [UO2 (NO3 )3 ]- was formed by adding tetramethylammonium
      nitrate to uranyl nitrate in acetonitrile medium. The luminescence features of
      this complex in acetonitrile are very sensitive to water content, which could
      lead to the use of it as a luminescent probe for water present in acetonitrile.
      The luminescence intensity ratio of 507 to 467 nm peak of uranyl tris nitrato
      showed a linear response in the range 0-5% (v/v) water content in acetonitrile.
      The present method was applied for three synthetic samples of acetonitrile for
      water detection and the results obtained were compared using Karl Fischer
      titration. There was a good agreement in the values obtained by both the methods.

PMID- 29356363
TI  - High-Performance Photovoltaic Detector Based on MoTe2 /MoS2 Van der Waals
      Heterostructure.
AB  - Van der Waals heterostructures based on 2D layered materials have received wide
      attention for their multiple applications in optoelectronic devices, such as
      solar cells, light-emitting devices, and photodiodes. In this work, high
      performance photovoltaic photodetectors based on MoTe2 /MoS2 vertical
      heterojunctions are demonstrated by exfoliating-restacking approach. The
      fundamental electric properties and band structures of the junction are revealed
      and analyzed. It is shown that this kind of photodetectors can operate under zero
      bias with high on/off ratio (>105 ) and ultralow dark current (~3 pA). Moreover,
      a fast response time of 60 us and high photoresponsivity of 46 mA W-1 are also
      attained at room temperature. The junctions based on 2D materials are expected to
      constitute the ultimate functional elements of nanoscale electronic and
      optoelectronic applications.

PMID- 29356364
TI  - The effect of hormone manipulations on sex ratios varies with environmental
      conditions in a turtle with temperature-dependent sex determination.
AB  - Exogenous application of steroids and related substances to eggs affects
      offspring sex ratios in species with temperature-dependent sex determination
      (TSD). Laboratory studies demonstrate that this effect is most pronounced near
      the constant temperature that produces 1:1 sex ratios (i.e., pivotal
      temperature). However, the impact of such chemicals on sex determination under
      natural nest temperatures (which fluctuate daily) is unknown, but could provide
      insight into the relative contributions of these two factors under natural
      conditions. We applied estradiol (E2) and an aromatase inhibitor (fadrozole) to
      eggs of the painted turtle (Chrysemys picta), a species with TSD, and allowed
      eggs to incubate under natural conditions during two field seasons (in 2012 and
      2013). Exogenous E2, fadrozole, and nest temperature contributed to variation in
      offspring sex ratio, but the relative contributions of these factors differed
      between years. In 2012, a much hotter than average season, sex ratios were
      heavily female biased regardless of nest temperature and chemical treatment.
      However, in 2013, a milder season, both nest temperature and chemical treatment
      were important. Moreover, a significant interaction between nest temperature and
      treatment demonstrated that exogenous estradiol induces female development
      regardless of nest temperature, but aromatase inhibition widens the range of
      temperatures that produces both sexes.

PMID- 29356365
TI  - Risk network approaches to locating undiagnosed HIV cases in Odessa, Ukraine.
AB  - INTRODUCTION: Providing HIV healthcare and Treatment as Prevention both depend on
      diagnosing HIV cases, preferably soon after initial infection. We hypothesized
      that tracing risk networks recruits higher proportions of undiagnosed positives
      than outreach-based testing or respondent-driven sampling (RDS) in Odessa,
      Ukraine. METHODS: The Transmission Reduction Intervention Project (TRIP) used
      risk network tracing to recruit sexual and injection networks of recently
      infected and longer-term infected (LTs) seeds (2013 to 2016). Integrated
      Biobehavioural Surveillance (IBBS) (2013) used RDS to recruit people who inject
      drugs (PWID). Outreach Testing tested PWID for HIV at community outreach sites
      (2013 to 2016). Proportions of undiagnosed positives among those tested were
      compared TRIP versus IBBS; TRIP versus Outreach Testing and between TRIP arms.
      Costs were compared across the projects. RESULTS: TRIP tested 1252 people (21%
      women) in seeds' risk networks; IBBS tested 400 (18% women); Outreach Testing
      13,936 (31% women). TRIP networks included a higher proportion of undiagnosed
      positives (14.6%) than IBBS (5.0%) or Outreach Testing (2.4%); odds ratio (OR)
      3.25 (95% CI 2.07, 5.12) versus IBBS and 7.03 (CI 5.95, 8.31) versus Outreach
      Testing respectively. Findings remained significant in analyses stratified by sex
      and when PWID in TRIP networks were compared with Outreach Testing and IBBS.
      Within TRIP, recently-infected participants' networks contained higher
      proportions of undiagnosed positives (16.3%) than LTs' networks (12.2%); OR 1.41
      (CI 1.01, 1.95). TRIP located undiagnosed positives less expensively than did RDS
      or Outreach Testing. CONCLUSIONS: TRIP's recruiting techniques, including
      prioritizing networks of the recently infected, find undiagnosed HIV-positive
      people efficiently. They should be integrated with standard practice to improve
      case-finding. Research should test these techniques in other socio-epidemiologic
      contexts. CLINICAL TRIAL REGISTRY: Registered ClinicalTrials.gov: NCT01827228.

PMID- 29356366
TI  - Choroidal thickness at age 66 years in the Danish high myopia study cohort 1948
      compared with follow-up data on visual acuity over 40 years: a clinical update
      adding spectral domain optical coherence tomography.
AB  - BACKGROUND AND PURPOSE: A population-based Copenhagen birth year 1948 cohort with
      high myopia recorded since age 14 years (spherical equivalent less than or
      equivalent to -6 D) has been followed over 50 years. Despite complications,
      current follow-ups have outlined a better visual prognosis than usually drawn
      from selected clinical series in the literature. For the present status at age 66
      years, focus was on visual ability and choroidal thickness. METHODS: Twenty-eight
      of the original 39 participants were available in 2014. Medical history was
      updated. Best-corrected visual acuity (BCVA) data were compared with subfoveal
      choroidal thickness (SFCT), now measured by enhanced depth optical coherence
      tomography. RESULTS: Due to at least better eye visual acuity (VA), all patients
      had maintained their everyday visual capacity. Only one participant was marginal
      regarding visual status for a driver's licence; low vision was not on record.
      Based on all eyes, choroidal thickness correlated negatively with axial length
      (AL), which also held for the fraction with high myopia (AL >26.5 mm). In high
      myopia, the mean choroidal subfoveal thickness was 114 +/- 75 MUm versus 182 +/-
      94 MUm in lower myopia (p = 0.01). CONCLUSION: Despite the generally maintained
      individual visual capacity in the series, significant correlation could be
      demonstrated between SFCT and (i) axial elongation and (ii) recorded VA, with a
      negative and a positive sign, respectively. Overall, the visual prognosis was
      relatively benign, in particular when compared with the selected high myopia
      hospital series that predominate in the ophthalmic literature.

PMID- 29356367
TI  - New horizons in congenital glaucoma surgery.

PMID- 29356369
TI  - Analysis of Economic and Environmental Aspects of Microalgae Biorefinery for
      Biofuels Production: A Review.
AB  - Microalgae are considered promising feedstock for the production of biofuels and
      other bioactive compounds, yet there are still challenges on commercial
      applications of microalgae-based products. This review focuses on the economic
      analysis, environmental impact, and industrial potential of biofuels production
      from microalgae. The cost of biofuels production remains higher compared to
      conventional fuel sources. However, integration of biorefinery pathways with
      biofuels production for the recovery of value-added products (such as
      antioxidants, natural dyes, cosmetics, nutritional supplements, polyunsaturated
      fatty acids, and so forth) could substantially reduce the production costs. It
      also paves the way for sustainable energy resources by significantly reducing the
      emissions of CO2 , NOx , SOx , and heavy metals. Large-scale biofuels production
      has yet to be successfully commercialized with many roadblocks ahead and heavy
      competition with conventional fuel feedstock as well as technological aspects.
      One of the prominent challenges is to develop a cost-effective method to achieve
      high-density microalgal cultivation on an industrial scale. The biofuels industry
      should be boosted by Government's support in the form of subsidies and
      incentives, for addressing the pressing climate change issues, achieving
      sustainability, and energy security.

PMID- 29356370
TI  - Prevalence and risk factors for problematic Internet use among rural adolescents
      in Korea.
AB  - INTRODUCTION: The number of Internet users is increasing dramatically due to high
      speed Internet connections and the use of cellular Internet service among rural
      adolescents in Korea. This study examined the prevalence of problematic Internet
      use (PIU) and factors associated with PIU among rural adolescents in Korea.
      METHODS: In total, 1168 adolescents aged 13 to 18 years from a rural area in
      Korea participated in this cross-sectional school survey. Problematic Internet
      use was categorized with Young's Internet Addiction Test using a validated
      cutoff. In addition, adolescents completed a self-report questionnaire, including
      questions on sociodemographic factors, the Center for Epidemiological Studies
      Depression Scale, and the State Anxiety Inventory for Children. Parents completed
      the Korean version of the Strengths and Difficulties Questionnaire (SDQ-P).
      RESULTS: Problematic Internet use was identified in 252 of 1168 (21.6%) students.
      Multivariate logistic analysis showed that male gender, academic stress, early
      exposure to the Internet, depression, and total difficulties on the SDQ-P were
      significantly associated with PIU. CONCLUSIONS: The findings indicate a need to
      develop preventive interventions for PIU among rural adolescents in Korea.

PMID- 29356371
TI  - Grounding as a Side-Effect of Grounding.
AB  - In relation to semantics, "grounding" has (at least) two relevant meanings.
      "Symbol grounding" is the process of connecting symbols (e.g., words) to
      perception and the world. "Communicative grounding" is the process of
      interactively adding to common ground in dialog. Strategies for grounding in
      human communication include, crucially, strategies for resolving troubles caused
      by various kinds of miscommunication. As it happens, these two processes of
      grounding are closely related. As a side-effect of grounding an utterance, dialog
      participants (DPs) may adjust the meanings they assign to linguistic expressions,
      in a process of semantic coordination. Meanings of at least some expressions
      (e.g., concrete nouns) include perceptual aspects which enable DPs to classify
      entities as falling under the expression or not based on their perception of
      those entities. We show how perceptual grounding of symbols can be achieved in a
      process of interactively adding to common ground. This requires that perceptual
      aspects of meaning can be updated as a result of participating in linguistic
      interaction, thereby enabling fine-grained semantic coordination of perceptually
      grounded linguistic meanings. A formal semantics for low-level perceptual aspects
      of meaning is presented, tying these together with the logical-inferential
      aspects of meaning traditionally studied in formal semantics. The key idea is to
      model perceptual meanings as classifiers of perceptual input. This requires a
      framework where intensions are (a) represented independently of extensions, and
      (b) structured objects which can be modified as a result of learning. We use Type
      Theory with Records (TTR), a formal semantics framework which starts from the
      idea that information and meaning are founded on our ability to perceive and
      classify the world, that is, to perceive objects and situations as being of
      types. As an example of our approach, we show how a simple classifier of spatial
      information based on the Perceptron can be cast in TTR.

PMID- 29356372
TI  - Rapid generation of three-dimensional microchannels for vascularization using a
      subtractive printing technique.
AB  - The development of tissue-engineered products has been limited by lack of a
      perfused microvasculature that delivers nutrients and maintains cell viability.
      Current strategies to promote vascularization such as additive three-dimensional
      printing techniques have limitations. This study validates the use of an ultra
      fast laser subtractive printing technique to generate capillary-sized channels in
      hydrogels prepopulated with cells by demonstrating cell viability relative to the
      photodisrupted channels in the gel. The system can move the focal spot laterally
      in the gel at a rate of 2500 mm/s by using a galvanometric scanner to raster the
      in plane focal spot. A Galilean telescope allows z-axis movement. Blended
      hydrogels of polyethylene glycol and collagen with a range of optical clarities,
      mechanical properties and swelling behavior were tested to demonstrate that the
      subtractive printing process for writing vascular channels is compatible with all
      of the blended hydrogels tested. Channel width and patterns were controlled by
      adjusting the laser energy and focal spot positioning, respectively. After
      treatment, high cell viability was observed at distances greater than or equal to
      18 MUm from the fabricated channels. Overall, this study demonstrates a flexible
      technique that has the potential to rapidly generate channels in tissue
      engineered constructs.

PMID- 29356373
TI  - Atmospheric Dry Hydrogen Plasma Reduction of Inkjet-Printed Flexible Graphene
      Oxide Electrodes.
AB  - This study concerns a low-temperature method for dry hydrogen plasma reduction of
      inkjet-printed flexible graphene oxide (GO) electrodes, an approach compatible
      with processes envisaged for the manufacture of flexible electronics. The
      processing of GO to reduced graphene oxide (rGO) was performed in 1-64 s, and sp2
      /sp2 +sp3 carbon concentration increased from approximately 20 % to 90 %. Since
      the plasma reduction was associated with an etching effect, the optimal reduction
      time occurred between 8 and 16 s. The surface showed good mechanical stability
      when deposited on polyethylene terephthalate flexible foils and significantly
      lower sheet resistance after plasma reduction. This method for dry plasma
      reduction could be important for large-area hydrogenation and reduction of GO
      flexible surfaces, with present and potential applications in a wide variety of
      emerging technologies.

PMID- 29356374
TI  - Effective Labeling of Primary Somatic Stem Cells with BaTiO3 Nanocrystals for
      Second Harmonic Generation Imaging.
AB  - While nanoparticles are an increasingly popular choice for labeling and tracking
      stem cells in biomedical applications such as cell therapy, their intracellular
      fate and subsequent effect on stem cell differentiation remain elusive. To
      establish an effective stem cell labeling strategy, the intracellular nanocrystal
      concentration should be minimized to avoid adverse effects, without compromising
      the intensity and persistence of the signal necessary for long-term tracking.
      Here, the use of second-harmonic generating barium titanate nanocrystals is
      reported, whose achievable brightness allows for high contrast stem cell labeling
      with at least one order of magnitude lower intracellular nanocrystals than
      previously reported. Their long-term photostability enables to investigate
      quantitatively at the single cell level their cellular fate in hematopoietic stem
      cells (HSCs) using both multiphoton and electron microscopy. It is found that the
      concentration of nanocrystals in proliferative multipotent progenitors is over
      2.5-fold greater compared to quiescent stem cells; this difference vanishes when
      HSCs enter a nonquiescent, proliferative state, while their potency remains
      unaffected. Understanding the nanoparticle stem cell interaction allows to
      establish an effective and safe nanoparticle labeling strategy into somatic stem
      cells that can critically contribute to an understanding of their in vivo
      therapeutic potential.

PMID- 29356375
TI  - Molecular characterization and tissue expression profiles of prepro-vasoactive
      intestinal peptide in the Chinese alligator (Alligator sinensis) during the
      active and hibernating periods.
AB  - The Chinese alligator (Alligator sinensis), a freshwater crocodilian endemic to
      China, is one of the most endangered crocodilian species; up to this date, very
      little is known about the endocrine regulation of its metabolic activities during
      different physiological states. In this study, we characterized the structure of
      the prepro-vasoactive intestinal peptide in Chinese alligator (prepro-caVIP) for
      the first time and examined its expression profiles in various tissues during the
      active and hibernating periods. The prepro-caVIP cDNA consists of a 221-bp 5'
      untranslated region (UTR), a 606-bp complete coding region (CDS), and a 312-bp 3'
      UTR, which encodes the 201-amino acid prepro-caVIP containing a 28-amino acid
      vasoactive intestinal peptide (VIP) and a 27-amino acid PHI (peptide histidine
      isoleucine). Multiple alignment analysis showed that VIP shares 100% identity
      with the given birds, reptiles, and African clawed frog, and 89% identity with
      mammals, 96% with fishes. Real-time quantitative PCR showed that the prepro-caVIP
      is widely expressed in all the examined tissues, and the expression level is
      significantly higher in small intestine, stomach, pancreas, lung, and skeletal
      muscle, whereas lower in heart, liver, spleen, kidney, ovary, and oviduct. During
      hibernation, the expression level of caVIP was significantly decreased in small
      intestine (P < 0.01), pancreas, and skeletal muscle (P < 0.05), whereas
      significantly increased in liver, spleen, and lung (P < 0.01). The wide
      distribution of caVIP and its differential expression changes in various tissues
      during hibernation implicated that it might play multiple effects in Chinese
      alligator and participate in the physiological adaptation of various organs in a
      paracrine and/or neurocrine manner.

PMID- 29356376
TI  - Boosting ART uptake and retention among HIV-infected pregnant and breastfeeding
      women and their infants: the promise of innovative service delivery models.
AB  - INTRODUCTION: With the rapid scale-up of antiretroviral treatment (ART) in the
      "Treat All" era, there has been increasing emphasis on using differentiated
      models of HIV service delivery. The gaps within the clinical cascade for mothers
      and their infants suggest that current service delivery models are not meeting
      families' needs and prompt re-consideration of how services are provided. This
      article will explore considerations for differentiated care and encourage the
      ongoing increase of ART coverage through innovative strategies while also
      addressing the unique needs of mothers and infants. DISCUSSION: Service delivery
      models should recognize that the timing of the mother's HIV diagnosis is a
      critical aspect of determining eligibility. Women newly diagnosed with HIV
      require a more intensive approach so that adequate counselling and monitoring of
      ART initiation and response can be provided. Women already on ART with evidence
      of virologic failure are also at high risk of transmitting HIV to their infants
      and require close follow-up. However, women stable on ART with a suppressed viral
      load before conception have a very low likelihood of HIV transmission and thus
      are strong candidates for multi-month ART dispensing, community-based
      distribution of ART, adherence clubs, community adherence support groups and
      longer intervals between clinical visits. A number of other factors should be
      considered when defining eligibility of mothers and infants for differentiated
      care, including location of services, viral load monitoring and duration on ART.
      To provide differentiated care that is client-centred and driven while
      encompassing a family-based approach, it will be critical to engage mothers,
      families and communities in models that will optimize client satisfaction,
      retention in care and quality of services. CONCLUSIONS: Differentiated care for
      mothers and infants represents an opportunity to provide client-centred care that
      reduces the burden on clients and health systems while improving the quality and
      uptake of services for families. However, with decreasing funding, stable HIV
      incidence, and aspirations for sustainability, it is critical to consider
      efficient, customized and cost-effective models of care for these populations as
      we aspire to eliminate mother-to-child transmission of HIV.

PMID- 29356377
TI  - Evidence of the sterility of allotetraploid Cobitis loaches (Teleostei,
      Cobitidae) using testes ultrastructure.
AB  - The diploid-polyploid populations of Cobitis distributed in Poland are usually
      composed of the spined loach Cobitis taenia or, less often, the Danubian loach C.
      elongatoides and their triploid (females) and tetraploid hybrids (females and
      males). The aim of this study was to determine whether tetraploid males
      participate in the reproduction process by analyzing their testis ultrastructure
      and the process of spermatogenesis in comparison with diploid males of both
      parental species. Tetraploid loaches were obtained from three different diploid
      polyploid populations distributed in Poland. The structure of Cobitis testes are
      typical for most Teleostei fish with cystic-type spermatogenesis. The successive
      stages of developing germ cells are enclosed within cysts formed by the Sertoli
      cells. This paper morphologically describes the different germ cell stages of
      spermatogenesis (spermatogonia, spermatocytes, spermatids, and spermatozoa) of C.
      taenia and C. elongatoides and provides a pioneering ultrastructural analysis of
      tetraploid Cobitis testes which reveals their unusual structure for the first
      time. Thus, cysts with normal spermatogonia and spermatocytes (pachyten or
      leptoten stages) containing synaptonemal complexes were present and no spermatids
      or spermatozoa were observed. Moreover, in contrast to previously analyzed
      diploid species, single cells or all of the cells within the cysts displayed
      chromatin condensation and/or chromatin fragmentation. The obtained results
      clearly demonstrated that tetraploid males are sterile and diploids are fertile
      and are the only sperm donors in the reproduction processes of diploid-polyploid
      Cobitis populations.

PMID- 29356378
TI  - Understanding Fundamentals and Reaction Mechanisms of Electrode Materials for Na
      Ion Batteries.
AB  - Development of efficient, affordable, and sustainable energy storage technologies
      has become an area of interest due to the worsening environmental issues and
      rising technological dependence on Li-ion batteries. Na-ion batteries (NIBs) have
      been receiving intensive research efforts during the last few years. Owing to
      their potentially low cost and relatively high energy density, NIBs are promising
      energy storage devices, especially for stationary applications. A fundamental
      understanding of electrode properties during electrochemical reactions is
      important for the development of low cost, high-energy density, and long shelf
      life NIBs. This Review aims to summarize and discuss reaction mechanisms of the
      major types of NIB electrode materials reported. By appreciating how the material
      works and the fundamental flaws it possesses, it is hoped that this Review will
      assist readers in coming up with innovative solutions for designing better
      materials for NIBs.

PMID- 29356379
TI  - Metabolic plasticity in development: Synergistic responses to high temperature
      and hypoxia in zebrafish, Danio rerio.
AB  - This study investigated interactions of temperature and hypoxia on metabolic
      plasticity and regulation in zebrafish, Danio rerio, in the first week of
      development. Larval morphometry, oxygen consumption, and metabolic responses to
      acute changes in temperature and oxygen were measured in larvae reared under four
      conditions, including control (28 degrees C and partial pressures of oxygen [PO2]
      of 21 kPa), high temperature (31 degrees C), hypoxia (11 kPa), and the two
      stressors combined. Rearing conditions did not result in consistent morphometric
      changes; substantial metabolic adjustments, however, were evident. While acute
      temperature increase resulted in elevated oxygen consumption, with a Q10 of 2.2
      +/- 0.08, early-staged larvae were able to compensate to chronic temperature rise
      as routine metabolic rates did not differ between 28 degrees C and 31 degrees C
      chronic treatments. In contrast, larval responses to chronic and acute hypoxia
      were similar, with ~30% decrease in metabolic rates from normoxic values at both
      temperatures. Further, prior exposure to chronic hypoxia in conjunction with
      acute high temperature increased Q10 by a factor of 2.5 from 2.2 +/- 0.08 to 5.6
      +/- 0.19. Metabolic suppression by acute hypoxia was independent of any prior
      exposure conditions. In short, results from this study showed that zebrafish
      larvae exhibited surprising temperature resilience and metabolic plasticity to a
      3 degrees C temperature rise even in their first week of life. Yet exposure to a
      second stressor (hypoxia) resulted in elevated sensitivity to temperature change
      that may lead to bioenergetic imbalance due to synergetic effects of temperature
      and hypoxia on metabolic rates.

PMID- 29356380
TI  - Phenylboronic Acid Derivatives as Validated Leads Active in Clinical Strains
      Overexpressing KPC-2: A Step against Bacterial Resistance.
AB  - The emergence and dissemination of multidrug resistant (MDR) pathogens resistant
      to nearly all available antibiotics poses a significant threat in clinical
      therapy. Among them, Klebsiella pneumoniae clinical isolates overexpressing KPC-2
      carbapenemase are the most worrisome, extending bacterial resistance to last
      resort carbapenems. In this study, we investigate the molecular recognition
      requirements in the KPC-2 active site by small phenylboronic acid derivatives.
      Four new phenylboronic acid derivatives were designed and tested against KPC-2.
      For the most active, despite their simple chemical structures, nanomolar affinity
      was achieved. The new derivatives restored susceptibility to meropenem in
      clinical strains overexpressing KPC-2. Moreover, no cytotoxicity was detected in
      cell-viability assays, which further validated the designed leads. Two
      crystallographic binary complexes of the best inhibitors binding KPC-2 were
      obtained at high resolution. Kinetic descriptions of slow binding, time-dependent
      inhibition, and interaction geometries in KPC-2 were fully investigated. This
      study will ultimately lead toward the optimization and development of more
      effective KPC-2 inhibitors.

PMID- 29356381
TI  - Biomechanical analysis of decellularized dermis and skin: Initial in vivo
      observations using optical cohesion tomography and vibrational analysis.
AB  - Measurement of the mechanical properties of skin in vivo has been complicated by
      the lack of methods that can accurately measure the viscoelastic properties
      without assuming values of Poisson's ratio and tissue density. In this paper, we
      present the results of preliminary studies comparing the mechanical properties of
      skin and scar tissue measured using a technique involving optical cohesion
      tomography (OCT) and vibrational analysis. This technique has been reported to
      give values of the modulus that correlate with those obtained from tensile
      measurements made on decellularized dermis (Shah et al., Skin Res Technol
      2016;23:399-406; Shah et al., J Biomed Mater Res Part 2017;105:15-22). The high
      correlation between moduli measured using vibrational studies and uniaxial
      tensile tests suggest that the modulus can be determined by measuring the natural
      frequency that occurs when a tissue is vibrated in tension. The results of
      studies on glutaric anhydride treated decellularized dermis suggest that
      vibrational analysis is a useful technique to look at changes in the properties
      of skin that occur after cosmetic and surgical treatments are used. Preliminary
      results suggest that the resonant frequency of scar tissue is much higher than
      that of adjacent normal skin reflecting the higher collagen content of scar. OCT
      in concert with vibrational analysis appears to be a useful tool to evaluate
      processes that alter skin properties in animals and humans as well to study the
      onset and pathogenesis of skin diseases such as cancer. This technique may be
      useful to evaluate the extent of wound healing in skin diabetic ulcers and other
      chronic skin conditions, scar tissue formation in response to implants, and other
      therapeutic treatments that alter skin properties. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1421-1427, 2018.

PMID- 29356382
TI  - Quenching of graphene quantum dots fluorescence by alkaline phosphatase activity
      in the presence of hydroquinone diphosphate.
AB  - In this work, a turn-off photoluminescent sensing proof-of-concept based on blue
      luminescent graphene quantum dots (GQDs) as the fluorescent probe was developed.
      For that purpose, GQDs optical response was related with the catalytic enzymatic
      activity of alkaline phosphatase (ALP), in the presence of hydroquinone
      diphosphate (HQDP). The hydrolysis of HQDP by ALP generated hydroquinone (HQ).
      The oxidation of HQ, enzymatically produced, to p-benzoquinone (BQ) resulted in
      the quenching of GQDs fluorescence (FL). Therefore, the developed luminescent
      sensing mechanism allowed the FL quenching with ALP activity to be related and
      thus quantified the concentration of ALP down to 0.5 nM of enzyme. This
      innovative design principle appears as a promising tool for the development of
      enzymatic sensors based on ALP labeling with fluorescent detection or even for
      direct ALP luminescent quantification in an easy, fast and sensitive manner.

PMID- 29356383
TI  - Does advanced lung inflammation index (ALI) have prognostic significance in
      metastatic non-small cell lung cancer?
AB  - BACKGROUND: Lung cancer is the most commonly diagnosed and death-related cancer
      type and is more frequent in males. Non-small-cell lung cancer (NSCLC) accounts
      for about 85% of all case. In this study, it was aimed to research the
      relationship between advanced lung inflammation index (ALI) and the primary mass
      maximum standardized uptake value (SUVmax) and C-reactive protein (CRP) at
      initial diagnosis and the prognostic value of ALI in determining the survival in
      metastatic NSCLC. METHODS: A total of 112 patients diagnosed as stage 4 non-small
      lung cancer in our hospital between January 2006 and December 2013 were included
      in this study. ALI was calculated as body mass index (BMI) * serum
      albumin/neutrophil-to-lymphocyte ratio (NLR). The patients were divided into two
      groups as ALI < 18 (high inflammation) and ALI >= 18 (low inflammation). The log
      rank test and Cox proportional hazard model were used to identify predictors of
      mortality. RESULTS: Evaluation was made of 94 male and 18 female patients with a
      mean age of 59.7 +/- 9.9 years. A statistically significant negative relationship
      was determined between ALI and CRP values (P < .001), but no relationship was
      found between ALI and SUVmax values (P = .436). The median survival time in
      patients with ALI < 18 was 12 months and, in those with ALI >= 18, it was 16
      months (P = .095). CONCLUSION: ALI is an easily calculated indicator of
      inflammation in lung cancer patients. Values <18 can be considered to predict a
      poor prognosis.

PMID- 29356384
TI  - Demographic and temporal variations in immunity and condition of polar bears
      (Ursus maritimus) from the southern Beaufort Sea.
AB  - Assessing the health and condition of animals in their natural environment can be
      problematic. Many physiological metrics, including immunity, are highly
      influenced by specific context and recent events to which researchers may be
      unaware. Thus, using a multifaceted physiological approach and a context-specific
      analysis encompassing multiple time scales can be highly informative.
      Ecoimmunological tools in particular can provide important indications to the
      health of animals in the wild. We collected blood and hair samples from free
      ranging polar bears (Ursus maritimus) in the southern Beaufort Sea and examined
      the influence of sex, age, and reproductive status on metrics of immunity,
      stress, and body condition during 2013-2015. We examined metrics of innate
      immunity (bactericidal ability and lysis) and stress (hair cortisol, reactive
      oxygen species, and oxidative barrier), in relation to indices of body condition
      considered to be short term (urea to creatinine ratio; UC ratio) and long term
      (storage energy and body mass index). We found the factors of sex, age, and
      reproductive status of the bear were critical for interpreting different
      physiological metrics. Additionally, the metrics of body condition were important
      predictors for stress indicators. Finally, many of these metrics differed between
      years, illustrating the need to examine populations on a longer time scale. Taken
      together, this study demonstrates the complex relationship between multiple
      facets of physiology and how interpretation requires us to examine individuals
      within a specific context.

PMID- 29356385
TI  - 3D Electronic Channels Wrapped Large-Sized Na3 V2 (PO4 )3 as Flexible Electrode
      for Sodium-Ion Batteries.
AB  - The development of portable and wearable electronics has aroused the increasing
      demand for flexible energy-storage devices, especially for the characteristics of
      high energy density, excellent mechanical properties, simple synthesis process,
      and low cost. However, the development of flexible electrodes for sodium-ion
      batteries (SIBs) is still limited due to the intricate production methods and the
      relatively high-cost of current collectors such as graphene/graphene oxide and
      carbon nanotubes. Here, the hierarchical 3D electronic channels wrapped large
      sized Na3 V2 (PO4 )3 is designed and fabricated by a simple electrospinning
      technique. As flexible electrode material, it exhibits outstanding electrolyte
      wettability, together with ultrafast electronic conductivity and high Na-ion
      diffusion coefficients for SIBs, leading to superior electrochemical
      performances. A high reversible specific capacity of 116 mA h g-1 (nearly 99% of
      the theoretical specific capacities) can be obtained at the current density of
      0.1 C. Even after a 300-fold current density increased (30 C), the discharge
      specific capacity of the flexible electrode still remains 63 mA h g-1 . Such an
      effective concept of fabricating 3D electronic channels for large-sized particles
      is expected to accelerate the practical applications of flexible batteries at
      various systems.

PMID- 29356386
TI  - Significance of tumor-associated autoantibodies in the early diagnosis of lung
      cancer.
AB  - OBJECTIVES: Autoantibodies tumor-associated antigens (TAAs) could be a valuable
      tool for the diagnosis or early detection of cancer due to their relatively high
      specificity and stability. The purpose of this study is to detect the level of
      tumor-associated autoantibodies in lung cancer and assess the diagnostic
      potential of autoantibodies in screening strategy for early stage lung cancer.
      MATERIALS AND METHODS: Levels of tumor-associated autoantibodies (AAbs) were
      measured against a panel of seven TAAs (p53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE
      and MAGEA1) in 397 patients with pulmonary lesions (305 with newly diagnosis of
      NSCLC, 47 with SCLC and 45 with benign nodule) and 74 control persons without any
      nodules in the lung after chest MDCT scan. The sensitivity, specificity for
      patients and control persons, positive rate of the panel in different pathology,
      stage, size of lesion, age and gender were compared and analyzed. RESULTS: The
      AAbs panel could distinguish malignant lesions from benign lesions and control
      people, with sensitivity of 56.53% and specificity of 91.60%. The specificity
      could be further increased to 95.80%, when combined with CT. The AAbs also showed
      high diagnostic value of malignant nodule, and it would be a new method for
      judgment of malignant nodules that are less than 8 mm in diameter. No significant
      differences were seen based on pathology, NSCLC stages, tumor size, age or
      gender. CONCLUSION: This assay confirms the value of AAbs panel as a diagnostic
      tool combined with CT scan.

PMID- 29356388
TI  - Analysis of the moment arms and kinematics of ostrich (Struthio camelus) double
      patellar sesamoids.
AB  - The patella ("kneecap") is a biomechanically important feature of the tendinous
      insertion of the knee extensor muscles, able to alter the moment arm lengths
      between its input and output tendons, and so modify the mechanical advantage of
      the knee extensor muscle. However, patellar gearing function is little-explored
      outside of humans, and the patella is often simplified or ignored in
      biomechanical models. Here, we investigate patellar gearing and kinematics in the
      ostrich-frequently used as an animal analogue to human bipedal locomotion and
      unusual in its possession of two patellae at the knee joint. We use x-ray
      reconstruction of moving morphology (XROMM) techniques to capture the kinematics
      of the patellae in an adult ostrich cadaver, passively manipulated in flexion
      extension. Moment arm ratios between the input and output tendons of each patella
      are calculated from kinematically determined centers of patellofemoral joint
      rotation. Both patellae are found to decrease the mechanical advantage of the
      extensor muscle-tendon complex, decreasing the tendon output force for a given
      muscle input force, but potentially increasing the relative speed of knee
      extension. Mechanically and kinematically, the proximal patella behaves similarly
      to the single patella of most other species, whereas the distal patella has
      properties of both a fixed retroarticular process and a moving sesamoid. It is
      still not clear why ostriches possess two patellae, but we suggest that the
      configuration in ostriches benefits their rapid locomotion and provides tendon
      protection.

PMID- 29356387
TI  - [(18-Crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4 ]0.5 : A Multifunctional Molecular
      Switch of Dielectric, Conductivity and Magnetic Properties.
AB  - Multifunctional materials that exhibit different physical properties in a single
      phase have potential for use in multifunctional devices. Herein, we reported an
      organic-inorganic hybrid compound [(18-crown-6)K][Fe(1)Cl(1)4 ]0.5 [Fe(2)Cl(2)4
      ]0.5 (1) by incorporating KCl and FeCl3 into a 18-crown-6 molecule, which acts as
      a host of the six O atoms providing a lone pair of electrons to anchor the guest
      potassium cation, and [FeCl4 ]- as a counterion for charge balance to construct a
      complex salt. This salt exhibited a one-step reversible structural transformation
      giving two separate high and low temperature phases at 373 K, which was confirmed
      by systematic characterizations including differential scanning calorimetry (DSC)
      measurements, variable-temperature structural analyses, and dielectric,
      impedance, variable-temperature magnetic susceptibility measurements.
      Interestingly, the structural transformation was coupled to both hysteretic
      dielectric phase transition, conductivity switch and magnetic-phase transition at
      373 K. This result gives an idea for designing a new type of phase-transition
      materials harboring technologically important magnetic, conductivity and
      dielectric properties.

PMID- 29356389
TI  - Somatic MECOM mosaicism in a patient with congenital bone marrow failure without
      a radial abnormality.

PMID- 29356390
TI  - Adherence to antiretroviral therapy for HIV/AIDS in Latin America and the
      Caribbean: Systematic review and meta-analysis.
AB  - INTRODUCTION: Optimal adherence to antiretroviral therapy is closely related with
      suppression of the HIV viral load in plasma, slowing disease progression and
      decreasing HIV transmission rates. Despite its importance, the estimated
      proportion of people living with HIV in Latin America and the Caribbean with
      optimal adherence has not yet been reported in a meta-analysis. Moreover, little
      is known of the factors leading to poor adherence which may be setting-specific.
      We present a pooled estimate of adherence to antiretroviral therapy (ART) of
      people living with HIV in Latin America and Caribbean, report the methods used to
      measure adherence and describe the factors associated with poor adherence among
      the selected studies. METHODS: We electronically searched published studies up to
      July 2016 on the PubMed, Web of Science and Virtual Health Library (Latin America
      and the Caribbean Regional Portal); considering the following databases: MEDLINE,
      LILACS, PAHO and IBECS. Two independent reviewers selected and extracted data on
      ART adherence and study characteristics. Pooled estimate of adherence was derived
      using a random-effects model. Risk of bias in individual studies was assessed
      independently by two investigators using the Risk of Bias Assessment tool for Non
      randomized Studies (RoBANS). RESULTS AND DISCUSSION: The meta-analysis included
      53 studies published between 2005 and 2016, which analysed 22,603 people living
      with HIV in 25 Latin America and Caribbean countries. Overall adherence in Latin
      America and Caribbean was 70% (95% CI: 63-76; I2  = 98%), similar to levels
      identified by studies conducted in high-income regions. Self-report was the most
      frequently used method to measure adherence. Subgroup analysis showed that
      adherence was higher for the shortest recall time frame used, as well as in
      countries with lower income level, Gross National Income (GNI) per capita and
      Human Development Index (HDI). Studies reported diverse adherence barriers, such
      as alcohol and substance misuse, depression, unemployment and pill burden.
      CONCLUSIONS: Our study suggests that adherence to ART in Latin America and
      Caribbean may be below the sufficient levels required for a successful long-term
      viral load suppression.

PMID- 29356391
TI  - A new HLA-C*05 allele, HLA-C*05:156, characterized by full-length hemizygous
      sequencing.
AB  - HLA-C*05:156 allele differs from C*05:01:01:02 by a nucleotide change in exon 2
      at codon 9.

PMID- 29356392
TI  - Transvenous dual-chamber pacemaker after paediatric heart transplantation using
      left ventricle pacing through the coronary sinus.
AB  - A 12-year-old child with end-stage heart failure due to restrictive
      cardiomyopathy was submitted to orthotopic heart transplantation. Primary graft
      dysfunction required venous arterial extra-corporeal membrane oxygenation. Heart
      function normalized, but complete atrioventricular block remained after 3 weeks.
      A dual-chamber pacing with transvenous left ventricle pacing through the coronary
      sinus was performed. At 5-year follow-up, the patient is stable with the same
      pacing system and with preserved ventricular function.

PMID- 29356393
TI  - Improvement of diagnostic performance of pathologists by reducing the number of
      pathologists responsible for thyroid fine needle aspiration cytology: An
      institutional experience.
AB  - BACKGROUND: Various efforts have been made to improve the diagnostic accuracy of
      thyroid fine needle aspiration (FNA) cytology. We changed the diagnostic system
      by reducing the number of pathologists responsible for the thyroid FNA cytology
      in the routine work, and analyzed the effect on the pathologist's diagnostic
      performance. METHODS: Since March 1, 2015, 3 pathologists have been responsible
      for diagnostic thyroid FNA, previously undertaken by 9 equally. We compared the
      prechange period (three months, 319 nodules) and the postchange period (12
      months, 1194 nodules). RESULTS: The turnaround time was shortened from 1.4 +/-
      0.7 days to 0.9 +/- 0.5 days (P < .001). The utilization rate of the Bethesda
      system for Reporting Thyroid Cytopathology (TBSRTC) increased from 92.5% to
      99.8%. Diagnostic rates of categories that are confirmative [II (benign) and VI
      (malignant)] increased, while the inadequate (I) or indeterminate (III)
      categories decreased. With category IV (follicular neoplasm), a challenging
      category in our country, an elevated malignancy rate was found at follow-up.
      Overall, the diagnostic performance was improved in terms of sensitivity (from
      98.5% to 99.2%) and specificity (from 94.4% to 98.4%), with reduced false
      negative rates (from 1.5% to 0.8%) and false-positive rates (from 2.9% to 1.1%).
      The area under the receiver operating characteristic curve increased from 0.861
      to 0.958. CONCLUSION: Reducing the number of pathologists responsible for
      diagnostic thyroid FNA cytology resulted in a higher utilization rate of TBSRTC,
      and more rapid and accurate diagnosis.

PMID- 29356394
TI  - Strike kinematics and performance in juvenile ball pythons (Python regius).
AB  - The rapid strike of snakes has interested researchers for decades. Although most
      work has focused on the strike performance of vipers, recent work has shown that
      other snakes outside of the Viperidae can strike with the same velocities and
      accelerations. However, to date all of these examples focus on performance in
      adult snakes. Here, we use high-speed video to measure the strike kinematics and
      performance of 10 juvenile (<6 months of age) ball pythons, Python regius. We
      find that juvenile P. regius strike at levels comparable to larger snakes, but
      with shorter durations and over shorter distances. We conclude that the juvenile
      P. regius maintain performance likely through manipulation of the axial
      musculature and accompanying elastic tissues, and that this is a first step to
      understanding ontogenetic changes in behavior and a potential avenue for
      understanding how captivity may also impact behavior.

PMID- 29356396
TI  - A multilocus association analysis method integrating phenotype and expression
      data reveals multiple novel associations to flowering time variation in wild
      collected Arabidopsis thaliana.
AB  - The adaptation to a new habitat often results in a confounding between genomewide
      genotype and beneficial alleles. When the confounding is strong, or the allelic
      effects is weak, it is a major statistical challenge to detect the adaptive
      polymorphisms. We describe a novel approach to dissect polygenic traits in
      natural populations. First, candidate adaptive loci are identified by screening
      for loci directly associated with the adaptive trait or the expression of genes
      known to affect it. Then, a multilocus genetic architecture is inferred using a
      backward elimination association analysis across all candidate loci with an
      adaptive false discovery rate-based threshold. Effects of population
      stratification are controlled by accounting for genomic kinship in both steps of
      the analysis and also by simultaneously testing all candidate loci in the
      multilocus model. We illustrate the method by exploring the polygenic basis of an
      important adaptive trait, flowering time in Arabidopsis thaliana, using public
      data from the 1,001 genomes project. We revealed associations between 33 (29)
      loci and flowering time at 10 (16) degrees C in this collection of natural
      accessions, where standard genomewide association analysis methods detected five
      (3) loci. The 33 (29) loci explained approximately 55.1 (48.7)% of the total
      phenotypic variance of the respective traits. Our work illustrates how the
      genetic basis of highly polygenic adaptive traits in natural populations can be
      explored in much greater detail using new multilocus mapping approaches taking
      advantage of prior biological information, genome and transcriptome data.

PMID- 29356395
TI  - Environmental calcium regulates gill remodeling in a euryhaline teleost fish.
AB  - Some cyprindid and cyprinidontiform fishes undergo gill remodeling via the
      proliferation or regression of an interlamellar cell mass (ILCM), resulting in
      the modification of gill surface area in response to environmental hypoxia or ion
      levels. We hypothesized that ion-related gill remodeling is regulated by water
      hardness through the interactions of Ca2+ with tight junctions, predicting that
      gills will exhibit a lower ILCM and more surface area in a high Ca2+ environment
      than in a low Ca2+ environment. To test this hypothesis, we acclimated euryhaline
      mangrove rivulus (Kryptolebias marmoratus) to natural hard water ([Ca2+] = 2.77
      mmol/L), low Ca2+ ([Ca2+] = 0.13 mmol/L) freshwater, or high Ca2+ water (5.88
      mmol/L). Fish exposed to hard water had a significantly lower ILCM height than
      fish exposed to low Ca2+ water. The addition of Ca2+ to low Ca2+ water restored
      gill surface area. Plasma Ca2+ activity was not significantly different between
      groups. This study provides support for an influence of external Ca2+ on gill
      remodeling and represents the first evidence of an ionic trigger (Ca2+) for gill
      remodeling in teleost fishes.

PMID- 29356397
TI  - Ingestive mastication in horses resembles rumination but not ingestive
      mastication in cattle and camels.
AB  - Horses achieve a higher degree of particle size reduction through ingestive
      mastication than functional ruminants. We characterized mastication using chew
      monitoring halters (RumiWatch) in six domestic horses, cattle, and Bactrian
      camels each. All animals were offered grass hay of the same batch for 15 min. In
      cattle and camels, measurements were continued after eating until rumination was
      observed. Except for one horse, 96% of the horses' ingestive mastication data
      were identified as "rumination" by the proprietary RumiWatch algorithm, whereas
      ingestion and rumination by cattle and camels were mostly classified correctly.
      There were no systematic differences between cattle and camels. In cattle and
      camels, ingestive mastication was less regular than rumination, indicated by
      significantly higher standard deviations of chewing peak intervals, peak heights,
      and peak breadths in intraindividual comparisons. The average standard deviations
      of these measures were lower in horses than in cattle and camel ingestive
      mastication, indicating a more consistent chewing pattern in horses. Horse values
      were similar to those of rumination mastication, suggesting equally regular
      chewing motions. Regular, rhythmic chewing represents a common feature of horses
      and functional ruminants, but the less uniform ingestive mastication in
      functional ruminants represents a deviating pattern, the adaptive value of which
      remains unclear. In particular, it does not appear to promote a higher ingestion
      rate. A potential cause may be the avoidance of high tooth wear rates by delaying
      a more regular, systematic mastication until ingesta has been softened and the
      grit has been washed off in the forestomach.

PMID- 29356398
TI  - Detection of peroxyl radicals from polluted air by free radical reaction combined
      with liquid chromatography signal amplification technique.
AB  - Free radicals play an important role in the oxidizing power of polluted air, the
      development of aging-related diseases, the formation of ozone, and the production
      of secondary particulate matter. The high variability of peroxyl radical
      concentration has prevented the detection of possible trends or distributions in
      the concentration of free radicals. We present a new method, free radical
      reaction combined with liquid chromatography photodiode array detection, for
      identifying and quantifying peroxyl radicals in polluted air. Functionalized
      graphene was used for loading peroxyl radicals and reactive molecules in air
      sampling system, which can facilitate reaction kinetics (charge transfers)
      between peroxyl radicals and reaction molecules. Separation was performed with
      and without a preliminary exposure of the polluted air sample to reactive
      molecule(s) system. The integral chromatographic peak areas before and after air
      sampling are used to quantify the atmospheric peroxyl radicals in polluted air.
      The utility of the new technique was tested with measurements carried out in the
      field.

PMID- 29356399
TI  - SALL4 - KHDRBS3 network enhances stemness by modulating CD44 splicing in basal
      like breast cancer.
AB  - Understanding the mechanism by which cancer cells enhance stemness facilitates
      cancer therapies. Here, we revealed that a stem cell transcription factor, SALL4,
      functions to enhance stemness in basal-like breast cancer cells. We used shRNA
      mediated knockdown and gene overexpression systems to analyze gene functions. To
      evaluate stemness, we performed a sphere formation assay. In SALL4 knockdown
      cells, the sphere formation ability was reduced, indicating that SALL4 enhances
      stemness. CD44 is a membrane protein and is known as a stemness factor in cancer.
      CD44 splicing variants are involved in cancer stemness. We discovered that SALL4
      modulates CD44 alternative splicing through the upregulation of KHDRBS3, a
      splicing factor for CD44. We cloned the KHDRBS3-regulated CD44 splicing isoform
      (CD44v), which lacks exons 8 and 9. CD44v overexpression prevented a reduction in
      the sphere formation ability by KHDRBS3 knockdown, indicating that CD44v is
      positively involved in cancer stemness. In addition, CD44v enhanced anoikis
      resistance under the control of the SALL4 - KHDRBS3 network. Basal-like breast
      cancer is an aggressive subtype among breast cancers, and there is no effective
      therapy so far. Our findings provide molecular targets for basal-like breast
      cancer therapy. In the future, this study may contribute to the establishment of
      drugs targeting cancer stemness.

PMID- 29356400
TI  - DNA Nanostructure-Based Systems for Intelligent Delivery of Therapeutic
      Oligonucleotides.
AB  - In the beginning of the 21st century, therapeutic oligonucleotides have shown
      great potential for the treatment of many life-threatening diseases. However,
      effective delivery of therapeutic oligonucleotides to the targeted location in
      vivo remains a major issue. As an emerging field, DNA nanotechnology is applied
      in many aspects including bioimaging, biosensing, and drug delivery. With
      sequence programming and optimization, a series of DNA nanostructures can be
      precisely engineered with defined size, shape, surface chemistry, and function.
      Simply with hybridization, therapeutic oligonucleotides including unmethylated
      cytosine-phosphate-guanine dinucleotide oligos, small interfering RNA (siRNA) or
      antisense RNA, single guide RNA of the regularly interspaced short palindromic
      repeat-Cas9 system, and aptamers, are successfully loaded on DNA nanostructures
      for delivery. In this progress report, the development history of DNA
      nanotechnology is first introduced, and then the mechanisms and means for
      cellular uptake of DNA nanostructures are discussed. Next, current approaches to
      deliver therapeutic oligonucleotides with DNA nanovehicles are summarized. In the
      end, the challenges and opportunities for DNA nanostructure-based systems for the
      delivery of therapeutic oligonucleotides are discussed.

PMID- 29356401
TI  - A genotype-phenotype association approach to reveal thermal adaptation in Daphnia
      galeata.
AB  - Altering thermal environments impose strong selection pressures on organisms,
      whose local persistence depends on adaptive phenotypic plastic and genetic
      responses. Thus far, adaptive change is monitored using phenotypic shifts or
      molecular markers, although inevitable obstacles are inherent in both methods. In
      order to circumvent these, it is necessary to find a causal link between adaptive
      alleles and fitness. Combining both approaches by linking genetic analyses and
      life-history measurements, a potential genotype-phenotype relationship can be
      assessed and adaptation at the molecular level demonstrated. For our study,
      clonal lineages of the freshwater keystone species D. galeata from seven
      different populations distributed along a latitudinal gradient across Europe were
      tested for local thermal adaptation in common garden experiments. Fitness-related
      life-history responses were quantified under different thermal regimes and
      experimental clones were genotyped at three candidate gene marker loci to
      investigate a potential genotype-phenotype association. The analyses of the life
      history data showed a significant temperature effect on several fitness-related
      life-history traits recorded in our experiments. However, we could not detect
      evidence for a direct association at neither candidate gene locus between
      genotypes and life-history traits. The observed phenotypic shifts might therefore
      not be based on the tested marker loci EA, M and TF, or in general not coding
      sequence-based and thus rather reveal phenotypic plasticity in response to
      thermal variation. Nonetheless, we revealed significant genotype by environment
      (GxE) interactions at all tested loci, potentially reflecting a contribution of
      marker loci to certain life-history trait values and contribution of multiple
      genetic loci to phenotypic traits.

PMID- 29356402
TI  - Captivity effects on immune response and steroid plasma levels of a Brazilian
      toad (Rhinella schneideri).
AB  - Stressors can increase plasma glucocorticoid (GC) levels and decrease plasma
      androgen levels in different species of vertebrates. GCs can have immune
      enhancing or immunosuppressive effects, which are dependent upon stress duration
      and intensity. The worldwide decline in amphibian populations is strongly linked
      to an array of different stressors. The impacts of stress on GCs, androgens, and
      the immune response are important to clarify and should lead to the better
      development of conservation strategies. The present study in adult male toads of
      Rhinella schneideri investigated the effects of captivity (7, 30, and 60 days) on
      plasma corticosterone (CORT) and plasma testosterone (T), as well as innate
      immune responses, specifically humoral and cell mediated responses, as indicated
      by bacterial killing ability (BKA) and phagocytosis by peritoneal cells,
      respectively. Captivity increased CORT threefold and decreased T versus controls.
      CORT maintained a threefold elevation throughout the captivity period, while body
      mass and T gradually decreased with time in captivity. BKA was lower at day 30,
      versus days 7 and 60, while peritoneal cell phagocytic efficiency decreased after
      day 30, remaining low at day 60. Moreover, phagocytosis efficiency was positively
      associated with T and body condition, suggesting that the effects of chronic
      stress on reproductive potential and immune response might be associated with the
      state of energetic reserves.

PMID- 29356403
TI  - Do sex reversal procedures differentially affect agonistic behaviors and sex
      steroid levels depending on the sexual genotype in Nile tilapia?
AB  - In Nile tilapia Oreochromis niloticus, phenotypic males and females with
      different sexual genotypes (XX, XY, YY) have particular behavioral and
      physiological traits. Compared to natural XX females and XY males, XY and YY
      females and XX males expressed higher level of aggressiveness that could be
      related to higher levels of 17beta-estradiol and 11-ketotestosterone,
      respectively. Our results suggest that the presence of a Y chromosome increases
      aggressiveness in females. However, since the same relationship between
      aggressiveness and the Y chromosome is not observed in males, we can hypothesize
      that the differences in aggressiveness are not directly dependent on the genotype
      but on the sex reversal procedures applied on young fry during their sexual
      differentiation to produce these breeders. These hormonal treatments could have
      permanently modified the development of the brain and consequently influenced the
      behavior of adults independently of their genotype. In both hypotheses (genotype
      or sex reversal influence), the causes of behavioral modifications have to be
      searched in an early modification of the brain sexual differentiation.

PMID- 29356405
TI  - Winter is coming: Diapause in the subtropical swallowtail butterfly Euryades
      corethrus (Lepidoptera, Papilionidae) is triggered by the shortening of day
      length and reinforced by low temperatures.
AB  - Diapause is modulated by genetic responses to some environmental cues. The most
      common stimulus to trigger diapause is photoperiod, but temperature and humidity
      can also be important. Subtropical grasslands insects are overexposed to
      seasonality and can use diapause as strategy to overcome harsh conditions,
      avoiding freezing winter temperatures and drought summer conditions. Here, we
      investigate if photoperiod, temperature, and humidity can induce and terminate
      dormancy using the model Euryades corethrus, a butterfly from Pampa that diapause
      as pupae. We hypothesize that photoperiod, temperature, and humidity can induce
      dormancy; to test the hypothesis, individuals from a stock population were
      subjected to experiments controlling these three factors. Photoperiod and
      temperature interactions were also tested. To evaluate if the removal of the
      harsh factor that induced diapause trigger diapause termination, 50% of dormant
      pupae in each experiment were exposed to amenable conditions. The results
      indicated that diapause is mainly induced by short photophases, while temperature
      and humidity separately do not increase dormancy frequency. Short photoperiods
      and low temperatures interact with each other, increasing dormancy in
      experimental populations. The evidences suggest that diapause is trigger by short
      day lengths and boosted by low temperatures as winter approaches. The incidence
      of obligatory summer diapause was not supported, but the occurrence of dormant
      pupae in high-temperature treatments suggests that high temperatures produce
      facultative diapause. Regarding diapause termination, the softening of harsh
      conditions that induced diapause was not sufficient to reverse the dormancy
      state, suggesting that diapause termination is more complex than previously
      thought, probably involving internal clocks.

PMID- 29356404
TI  - Utility of perioperative skin perfusion pressure measurement for treatment of
      ulcers caused by arteriovenous access ischaemic steal.
AB  - Arteriovenous access ischaemic steal is a serious complication following
      arteriovenous fistula (AVF) construction. The aim of treatment is to improve
      distal circulation without impairing the function of the fistula. Therefore, any
      repair should be performed with intraoperative monitoring. We report 2 cases of
      this disorder treated using perioperative measurement of skin perfusion pressure
      (SPP) for preoperative surgical planning and intraoperative guidance. A 73-year
      old woman with a left cubital AVF developed gangrene of the tip of the left
      little finger. Arteriovenous access ischaemic steal was suspected. The SPP of the
      little finger was 18 mm Hg, which increased to 65 mm Hg after manual occlusion of
      the fistula. A 58-year-old woman with a left antebrachial AVF had gangrene of the
      tip of the left middle finger. The SPP was 19 mm Hg, and steal syndrome was
      suspected based on angiography and the SPP with manual occlusion of the fistula.
      In both cases, serial plication of the fistula was performed based on
      intraoperative perfusion pressure monitoring, leading to the successful
      resolution of the ischaemic steal syndrome. In both cases, haemodialysis could be
      continued through the repaired fistula.

PMID- 29356406
TI  - Origin of sex chromosomes in six groups of Rana rugosa frogs inferred from a sex
      linked DNA marker.
AB  - Each vertebrate species, as a general rule, has either the XX/XY or ZZ/ZW
      chromosomes by which sex is determined. However, the Japanese Rana (R.) rugosa
      frog is an exception, possessing both sex-determining combinations within one
      species, varying with region of origin. We collected R. rugosa frogs from 104
      sites around Japan and South Korea and determined the nucleotide sequences of the
      mitochondrial 12S ribosomal RNA gene. Based on the sequences, R. rugosa frogs
      were divided into four groups from Japan and one from South Korea. The ZZ/ZW type
      is reportedly derived from the XX/XY type, although recently a new ZZ/ZW type of
      R. rugosa was reported. However, it still remains unclear from where the sex
      chromosomes in the five groups of this species were derived. In this study, we
      successfully isolated a sex-linked DNA maker and used it to classify R. rugosa
      frogs into several groupings. From the DNA marker as well as from nucleotide
      analysis of the promoter region of the androgen receptor (AR) gene, we identified
      another female heterogametic group, designated, West-Central. The sex chromosomes
      in the West-Central originated from the West and Central groups. The results
      indicate that a sex-linked DNA marker is a verifiable tool to determine the
      origin of the sex chromosomes in R. rugosa frogs in which the sex-determining
      system has changed, during two independent events, from the male to female
      heterogamety.

PMID- 29356407
TI  - Condition dependence of shared traits differs between sympatric Anolis lizards.
AB  - In many species, sexually selected combat and display traits can confer dramatic
      fitness benefits to males by aiding in mate acquisition, so individuals maximally
      invest energy into their growth and maintenance. Such traits are deemed condition
      dependent, as the energy that is available for investment depends on the health
      and condition of the individual. Condition dependence is present in a wide range
      of traits across many taxa, but the extent to which condition dependence varies
      among shared traits in closely related species is poorly understood. We tested
      for condition dependence in two Anolis lizards, the ground anole (Anolis humilis)
      and the slender anole (Anolis limifrons). Specifically, we measured dewlap area,
      jaw length, jaw width, and sprint speed, and then regressed one of two indices of
      body condition on each of these traits for both species. We found that dewlap
      area and jaw width exhibited condition dependence in ground anoles, but not in
      slender anoles. Sprint speed and jaw length were not condition-dependent in
      either species. The presence of condition dependence in ground anoles, but not
      slender anoles, implies evolutionary liability in the condition dependence of
      shared traits. Additionally, the fact that condition dependence was only detected
      in ground anoles, which have a greater relative dewlap size, suggests a potential
      role for signal evolution or strength of sexual selection in the evolution of
      condition dependence. Finally, our research suggests that variation in condition
      dependence of sexually selected traits could have implications for the evolution
      of dewlap diversity among Anolis species.

PMID- 29356408
TI  - Emerging Novel Metal Electrodes for Photovoltaic Applications.
AB  - Emerging novel metal electrodes not only serve as the collector of free charge
      carriers, but also function as light trapping designs in photovoltaics. As a
      potential alternative to commercial indium tin oxide, transparent electrodes
      composed of metal nanowire, metal mesh, and ultrathin metal film are intensively
      investigated and developed for achieving high optical transmittance and
      electrical conductivity. Moreover, light trapping designs via patterning of the
      back thick metal electrode into different nanostructures, which can deliver a
      considerable efficiency improvement of photovoltaic devices, contribute by the
      plasmon-enhanced light-mattering interactions. Therefore, here the recent works
      of metal-based transparent electrodes and patterned back electrodes in
      photovoltaics are reviewed, which may push the future development of this
      exciting field.

PMID- 29356409
TI  - Scalable Synthesis of Triple-Core-Shell Nanostructures of TiO2 @MnO2 @C for High
      Performance Supercapacitors Using Structure-Guided Combustion Waves.
AB  - Core-shell nanostructures of metal oxides and carbon-based materials have emerged
      as outstanding electrode materials for supercapacitors and batteries. However,
      their synthesis requires complex procedures that incur high costs and long
      processing times. Herein, a new route is proposed for synthesizing triple-core
      shell nanoparticles of TiO2 @MnO2 @C using structure-guided combustion waves
      (SGCWs), which originate from incomplete combustion inside chemical-fuel-wrapped
      nanostructures, and their application in supercapacitor electrodes. SGCWs
      transform TiO2 to TiO2 @C and TiO2 @MnO2 to TiO2 @MnO2 @C via the incompletely
      combusted carbonaceous fuels under an open-air atmosphere, in seconds. The
      synthesized carbon layers act as templates for MnO2 shells in TiO2 @C and organic
      shells of TiO2 @MnO2 @C. The TiO2 @MnO2 @C-based electrodes exhibit a greater
      specific capacitance (488 F g-1 at 5 mV s-1 ) and capacitance retention (97.4%
      after 10 000 cycles at 1.0 V s-1 ), while the absence of MnO2 and carbon shells
      reveals a severe degradation in the specific capacitance and capacitance
      retention. Because the core-TiO2 nanoparticles and carbon shell prevent the
      deformation of the inner and outer sides of the MnO2 shell, the nanostructures of
      the TiO2 @MnO2 @C are preserved despite the long-term cycling, giving the
      superior performance. This SGCW-driven fabrication enables the scalable synthesis
      of multiple-core-shell structures applicable to diverse electrochemical
      applications.

PMID- 29356410
TI  - Neonatal swallowing assessment using fiberoptic endoscopic evaluation of
      swallowing (FEES).
AB  - OBJECTIVES: Swallowing disorders which lead to aspiration are common in premature
      infants with a postmenstrual age (PMA) of >36 weeks. Aspiration is often silent
      and the unique symptom is desaturation during feeding. The aim of this study was
      1) to determine the number of prematures with desaturations during feeding due to
      aspiration, using Fiberoptic Endoscopic Evaluation of Swallowing (FEES); 2) to
      relate clinical factors and FEES findings to aspiration; and 3) to describe type
      and efficacy of suggested treatments. METHODS: A retrospective review of 62 ex
      premature babies with a median PMA of 40 weeks which underwent FEES due to
      persistent feeding desaturations. Aspiration was related to other FEES findings
      and to clinical and demographic data. The efficacy of the treatment was evaluated
      during the FEES and by comparing recorded desaturations during feeding 7 days
      before and after FEES. RESULTS: A total of 44 (71%) infants were diagnosed with
      aspiration and/or penetration. No relation was found to demographic or clinical
      data. The accumulation of saliva and residues post-swallowing were related to
      aspiration (P < 0.01). In 77.3% of the infants, use of a thickener seemed to
      reduce aspiration during FEES and was suggested as a treatment. 13.6% of infants
      received anti-reflux treatment after FEES and 9.1% required gastrostomy.
      CONCLUSIONS: Aspiration is very frequent in premature infants who present
      desaturations during feeding and FEES is a useful method for diagnosing and
      suggesting treatments.

PMID- 29356411
TI  - Silicon-Based Anodes for Lithium-Ion Batteries: From Fundamentals to Practical
      Applications.
AB  - Silicon has been intensively studied as an anode material for lithium-ion
      batteries (LIB) because of its exceptionally high specific capacity. However,
      silicon-based anode materials usually suffer from large volume change during the
      charge and discharge process, leading to subsequent pulverization of silicon,
      loss of electric contact, and continuous side reactions. These transformations
      cause poor cycle life and hinder the wide commercialization of silicon for LIBs.
      The lithiation and delithiation behaviors, and the interphase reaction
      mechanisms, are progressively studied and understood. Various nanostructured
      silicon anodes are reported to exhibit both superior specific capacity and cycle
      life compared to commercial carbon-based anodes. However, some practical issues
      with nanostructured silicon cannot be ignored, and must be addressed if it is to
      be widely used in commercial LIBs. This Review outlines major impactful work on
      silicon-based anodes, and the most recent research directions in this field,
      specifically, the engineering of silicon architectures, the construction of
      silicon-based composites, and other performance-enhancement studies including
      electrolytes and binders. The burgeoning research efforts in the development of
      practical silicon electrodes, and full-cell silicon-based LIBs are specially
      stressed, which are key to the successful commercialization of silicon anodes,
      and large-scale deployment of next-generation high energy density LIBs.

PMID- 29356412
TI  - DNA Nanotubes with Hydrophobic Environments: Toward New Platforms for Guest
      Encapsulation and Cellular Delivery.
AB  - Natural systems combine different supramolecular interactions in a hierarchical
      manner to build structures. In contrast, DNA nanotechnology relies almost
      exclusively on DNA base pairing for structure generation. Introducing other
      supramolecular interactions can expand the structural and functional range of DNA
      assemblies, but this requires an understanding of the interplay between these
      interactions. Here, an economic strategy to build DNA nanotubes functionalized
      with lipid-like polymers is reported. When these polymers are linked to the
      nanotube using a spacer, they fold inside to create a hydrophobic environment
      within the nanotube; the nanotube can encapsulate small molecules and
      conditionally release them when specific DNA strands are added, as monitored by
      single-molecule fluorescence microscopy. When the polymers are directly linked to
      the nanostructure without spacers, they interact intermolecularly to form a
      network of DNA bundles. This morphological switch can be directly observed using
      a strand displacement strategy. The two association modes result in different
      cellular uptake behavior. Nanotubes with internal hydrophobic association show
      dye-mediated mitochondrial colocalization inside cells; while the bundles
      disassemble into smaller polymer-coated structures that reduce the extent of
      nonspecific cellular uptake. This approach uncovers parameters to direct the
      hierarchical assembly of DNA nanostructures, and produces promising materials for
      targeted drug delivery.

PMID- 29356413
TI  - Noble Metal-Free Nanocatalysts with Vacancies for Electrochemical Water
      Splitting.
AB  - The fast development of nanoscience and nanotechnology has significantly advanced
      the fabrication of nanocatalysts and the in-depth study of the structural
      activity characteristics of materials at the atomic level. Vacancies, as typical
      atomic defects or imperfections that widely exist in solid materials, are
      demonstrated to effectively modulate the physicochemical, electronic, and
      catalytic properties of nanomaterials, which is a key concept and hot research
      topic in nanochemistry and nanocatalysis. The recent experimental and theoretical
      progresses achieved in the preparation and application of vacancy-rich
      nanocatalysts for electrochemical water splitting are explored. Engineering of
      vacancies has shown to open up a new avenue beyond the traditional morphology,
      size, and composition modifications for the development of nonprecious
      electrocatalysts toward efficient energy conversion. First, an introduction
      followed by discussions of different types of vacancies, the approaches to create
      vacancies, and the advanced techniques widely used to characterize these
      vacancies are presented. Importantly, the correlations between the vacancies and
      activities of the vacancy-rich electrocatalysts via tuning the electronic states,
      active sites, and kinetic energy barriers are reviewed. Finally, perspectives on
      the existing challenges along with some opportunities for the further development
      of vacancy-rich noble metal-free electrocatalysts with high performance are
      discussed.

PMID- 29356414
TI  - Bidirectional influences of caregiver utterances and supported joint engagement
      in children with and without autism spectrum disorder.
AB  - : This study examined sequential associations between pairs of caregiver talk and
      caregiver-child joint engagement categories. Sequential associations quantify the
      extent to which one event (such as a particular type of caregiver talk) follows
      another event (such as a particular type of joint engagement) in a pre-specified
      time window, while controlling for the chance occurrence of the sequence.
      Although unable to support strong conclusions about causality, the requirement of
      sequential analysis that key events occur within a close temporal sequence rules
      out alternative explanation for associations that summary-level correlations
      cannot. We applied sequential analysis to observational data on 98 caregiver
      child dyads, fifty of which included a child with autism spectrum disorder (ASD).
      Groups were matched on mental age, and all were just beginning to develop spoken
      vocabulary. Sequential associations between supported joint engagement and
      caregiver follow-in utterances were stronger in ASD dyads as compared to dyads
      with typically developing children. Further, sequential associations between
      utterances related to the child's focus of attention followed by higher order
      supported joint engagement (HSJE) were stronger than between utterances that
      related to the caregiver's focus of attention and HSJE, across both groups.
      Finally, sequential associations between follow-in directives followed by HSJE
      were stronger than between follow-in comments followed by HSJE, again across both
      groups of children. Autism Res 2018, 11: 755-765. (c) 2018 International Society
      for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Our findings suggest
      that caregivers of children with autism spectrum disorder (ASD) may be
      particularly adept at timing their talk to follow moments of high-level joint
      engagement, and that follow-in directives are particularly facilitative of high
      level joint engagement. Future intervention work can capitalize on these findings
      to support high level caregiver-child engagement around toys, which may promote
      development in children with ASD.

PMID- 29356415
TI  - Clinical and imaging spectrum of tuberculosis-associated fibrosing mediastinitis.
AB  - PURPOSE: Fibrosing mediastinitis (FM) is a rare disorder characterized by an
      excessive fibrotic reaction within the mediastinum, which can result in
      compression of mediastinal structures. To investigate the clinical and imaging
      characteristics of TB-associated FM, patients with evidence of TB infection were
      retrospectively evaluated in this study. MATERIALS AND METHODS: A total of 33
      patients with clinically diagnosed FM and evidence of TB infection were selected
      from the database of two institutional medical centers. Medical records were
      reviewed to evaluate the clinical disease spectrum, responses to therapy and
      imaging characteristics. RESULTS: TB-associated FM showed distinctive
      infiltrative pattern on chest CT, such as bilateral involvement and hilar
      predominance. The majority of patients presented with nonspecific respiratory
      symptoms due to the compression of mediastinal broncho-vascular structures.
      Echocardiography discovered pulmonary hypertension to various degrees in 60% of
      patients. Although only a part of patients responded to medical therapy, they
      seldom showed deterioration during the follow-up. CONCLUSIONS: TB-associated FM
      shows some specific imaging characteristics, reflecting immune-mediated fibrotic
      reaction secondary to TB infection. The insidious progression to mediastinal
      fibrosis after TB infection poses a challenge to the early diagnosis and results
      in subsequent respiratory dysfunction and pulmonary hypertension.

PMID- 29356416
TI  - A neuropathological study of novel RTTN gene mutations causing a familial
      microcephaly with simplified gyral pattern.
AB  - BACKGROUND: The RTTN gene encodes Rotatin, a large centrosomal protein involved
      in ciliary functions. RTTN mutations have been reported in seven families and are
      associated with two phenotypes: polymicrogyria associated with seizures and
      primary microcephaly associated with primordial dwarfism. CASE: A targeted exome
      sequencing of morbid genes causing cerebral malformations identified novel RTTN
      compound heterozygous mutations in a family where three pregnancies were
      terminated because a severe fetal microcephaly was diagnosed. An autopsy
      performed on the second sib showed moderate growth restriction and a microcephaly
      with simplified gyral pattern. The histopathological study discovered a malformed
      cortical plate. CONCLUSIONS: The present study confirms the involvement of RTTN
      gene mutations in microcephaly with simplified gyral pattern and describes the
      observed abnormal neuropathological findings.

PMID- 29356417
TI  - Fostering Spontaneous Visual Attention in Children on the Autism Spectrum: A
      Proof-of-Concept Study Comparing Singing and Speech.
AB  - : Children on the autism spectrum are reported to have lower rates of social gaze
      as early as toddlerhood, and this pattern persists across the lifespan. Finding
      ways to promote more natural and spontaneous engagement in social interactions
      may help to boost developmental opportunities in the child's home and community
      settings. This proof-of-concept study hypothesized that a video of a singer would
      elicit more attention to the performer, particularly to her face, than a video of
      her reading a story, and that the child's familiarity with the material would
      enhance attention. Sixteen children on the autism spectrum (7-10 years old)
      watched 4 videos 1 min long comprising a favorite song or story, and an
      unfamiliar song and story. Eye movements were recorded, and three-way repeated
      measures ANOVAs examined the proportion of total valid visual dwell time and
      fixations, in each trial and each target area. For proportion of both dwell time
      and fixation counts, children were significantly more likely to look at the
      performer's face and body and less at the prop during singing than story-telling
      and when familiar rather than unfamiliar material was presented. These findings
      raise important issues for supporting children to naturally initiate looking
      toward a person's face. Autism Res 2018, 11: 732-737. (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Children on the
      autism spectrum may have difficulty looking at people, particularly their faces.
      In this study, children watched videos of someone singing or reading a story. The
      results show that children look more at the person if they were singing and if
      the story was familiar to them. Using songs and familiar stories may be a way to
      help children with autism to naturally engage with others.

PMID- 29356418
TI  - Electrolytes, SEI Formation, and Binders: A Review of Nonelectrode Factors for
      Sodium-Ion Battery Anodes.
AB  - Through intense effort in recent years, knowledge of Na-ion batteries has been
      advanced significantly, pertaining to electrodes. Often, such progress has been
      accompanied by using a convenient choice of electrolyte or binder. Nevertheless,
      it has been witnessed that "external" factors to electrodes, such as
      electrolytes, solid electrolyte interphase, and binders, affect the functions of
      electrodes profoundly. And generally, certain types of electrodes favor some
      electrolytes or binders. With a rapidly increasing number of publications in the
      area, trends in terms of electrolytes and binders are possibly exploitable.
      Unfortunately, the field has yet to see a review article that devotes itself to
      these nonelectrode aspects of Na-ion batteries. Here, the gap is filled by
      conducting a comprehensive review of these nonelectrode external factors,
      especially by looking into their correlation with electrochemical properties,
      such as cycle life, and first cycle coulombic efficiency. Not only are the
      representative reports reviewed, but also quantitative analyses on the database
      that are constructed are provided. With such analyses, some new data-driven
      perspectives are postulated, which are of great value to the community.

PMID- 29356419
TI  - Photoacoustic-Enabled Self-Guidance in Magnetic-Hyperthermia Fe@Fe3 O4
      Nanoparticles for Theranostics In Vivo.
AB  - Magnetic nanoparticles have gained much interest for theranostics benefited from
      their intrinsic integration of imaging and therapeutic abilities. Herein,
      c(RGDyK) peptide PEGylated Fe@Fe3 O4 nanoparticles (RGD-PEG-MNPs) are developed
      for photoacoustic (PA)-enabled self-guidance in tumor-targeting magnetic
      hyperthermia therapy in vivo. In the alphav beta3 -positive U87MG glioblastoma
      xenograft model, the PA signal of RGD-PEG-MNPs reaches its maximum in the tumor
      at 6 h after intravenous administration. This signal is enhanced by 2.2-folds
      compared to that of the preinjection and is also 2.2 times higher than that in
      the blocking group. It demonstrates the excellent targeting property of RGD-PEG
      MNPs. With the guidance of the PA, an effective magnetic hyperthermia to tumor is
      achieved using RGD-PEG-MNPs.

PMID- 29356420
TI  - Copy number variation of a protease gene of Daphnia: Its role in population
      tolerance.
AB  - Copy number variation (CNV) of genes coding for certain enzymes has been shown to
      be responsible for adaptation of arthropods to anthropogenic toxins. Natural
      toxins produced by cyanobacteria in freshwater ecosystems, that is, protease
      inhibitors (PIs), have been demonstrated to increase in frequency over the last
      decades due to eutrophication and global warming. These PIs inhibit digestive
      proteases of Daphnia, the major herbivore of phytoplankton and cyanobacteria. The
      adjustment of isoforms, differences in gene expression, and activity of gut
      proteases determine tolerance to dietary PIs in single Daphnia genotypes. Here,
      we tested whether similar mechanisms are also responsible for differences in
      tolerance among Daphnia population. We developed a droplet digital PCR (ddPCR)
      method for the analysis of CNV of Daphnia proteases. We report that one Daphnia
      protease gene showed CNV between populations and that CNV correlates with
      chymotrypsin gene expression among populations. We showed that populations of
      Daphnia magna differ in tolerance to cyanobacterial PIs according to the
      cyanobacterial background of their lake of origin, which hints at local
      adaptation. The tolerance of the populations correlates with IC50 values of their
      chymotrypsins, which is probably due to a combined effect of CNV (translating
      into gene expression differences) and positive selection of tolerant protease
      isoforms. This is the first study using ddPCR to demonstrate CNV of a gene with
      ecologically relevant function, and the first report of differences in tolerance
      to cyanobacterial PIs among Daphnia populations in combination with the
      assessment of underlying molecular mechanisms.

PMID- 29356421
TI  - Repeated immune challenges affect testosterone but not sperm quality.
AB  - Mounting an immunological response is energetically demanding and necessarily
      redirects allocation of resources toward immune system activation and away from
      other energetically expensive processes, such as reproduction. Lipopolysaccharide
      (LPS), a major component of the outer membrane of the cell wall of Gram-negative
      bacteria Escherichia coli, mimics a bacterial infection without producing the
      cost of replicating the pathogen and is one of the most commonly used agents to
      induce an acute phase immune response. Here, we ask if a trade-off can be induced
      between activation of the acute phase immune response and sperm function, a key
      indicator of sperm competitive ability. Further, we ask whether repeated exposure
      to this endotoxin in a social species such as the house sparrow (Passer
      domesticus), where repeated pathogen exposure may be common, may have a more
      pronounced effect. To address our questions, we exposed individuals to two rounds
      of LPS treatment or control, to mimic a repeated pathogen exposure in the wild.
      We predicted that repeated pathogen exposure would have detrimental effects on
      sperm quality, and therefore, reproductive success. We compared a measure of
      sperm quality (straight-line velocity) in captive male house sparrows between LPS
      treated and control individuals. We found that although LPS treatment impaired
      circulating testosterone and induced a hypothermic state when compared with
      controls, it did not affect sperm quality within days or weeks following a single
      or repeated LPS exposure.

PMID- 29356422
TI  - The effects of potassium and muscle homogenate on proprioceptive responses in
      crayfish and crab.
AB  - Proprioception of limbs and joints is a basic sensory function throughout most of
      the animal kingdom. It is important to understand how proprioceptive organs and
      the associated sensory neurons function with altered environments such as
      increased potassium ion concentrations ([K+]) from diseased states, ionic
      imbalances, and damaged tissues. These factors can drastically alter neuronal
      activity. To assess this matter, we used the chordotonal organ in a walking leg
      of a blue crab (Callinectes sapidus) and the muscle receptor organ of the
      crayfish (Procambarus clarkii). These organs serve as tractable models for the
      analysis of proprioception. The preparations can help serve as translational
      models for these effects, which may be observed in other invertebrate species as
      well as mammalian species (including humans). When extracellular potassium
      concentration ([K+]o) is increased to 20 mM in both preparations, mixed results
      are observed with activity increasing in some preparations and decreasing in
      others after mechanical displacement. However, when [K+]o is increased to 40 mM,
      activity drastically decreases in all preparations. Additionally, proprioceptor
      sensory activity declines upon exposure to a diluted muscle homogenate, which
      contains a host of intracellular constituents. The robust effects of altered [K+]
      on proprioception in these models illuminate the potential detriments on neuronal
      function in cases of severe tissue damage as well as altered [K+]o.

PMID- 29356423
TI  - Introduction to ecoimmunology: An integrative approach.

PMID- 29356424
TI  - Immune variation during pregnancy suggests immune component-specific costs of
      reproduction in a viviparous snake with disparate life-history strategies.
AB  - Growing evidence suggests the existence of trade-offs between immune function and
      reproduction in diverse taxa. Among vertebrates, however, there is still a
      taxonomic bias toward studies in endotherms, particularly birds. We tested the
      hypothesis that reproduction entails immune-related costs in the viviparous
      garter snake, Thamnophis elegans, from populations that exhibit two life-history
      strategies, termed ecotypes, with contrasting paces of life. Between the two
      ecotypes, we predicted lower immune function in gravid than non-gravid females of
      both strategies, but with relatively larger immunity costs in the ecotype that
      generally invests more in current reproduction. Across individuals, we predicted
      greater immune costs for females investing more in the present specific
      reproductive event (i.e., higher fecundity) irrespective of their ecotype. We
      assessed leukocyte profiles and measured bactericidal capacity of plasma (innate
      immunity) and T- and B-lymphocyte proliferation (adaptive immunity) in gravid and
      non-gravid females in their natural habitats. We also collected data on
      reproductive output from these same gravid females brought into captivity. Gravid
      females of both ecotypes showed lower T-lymphocyte proliferation responses to
      concanavalin A than non-gravid females, but no differential costs were observed
      between ecotypes. The remaining immune variables did not vary between gravid and
      non-gravid females. Among gravid females within each ecotype, those with larger
      reproductive output showed lower total leukocyte counts, suggesting a fecundity
      dependent trade-off. Our study contributes to the comparative ecoimmunology of
      vertebrates by highlighting the immune component-specificity of trade-offs
      between reproduction and immune function and showing that costs can be fecundity
      dependent in some, but not all cases.

PMID- 29356426
TI  - The effects of acclimation temperature, salinity, and behavior on the thermal
      tolerance of Mozambique tilapia (Oreochromis mossambicus).
AB  - Mozambique tilapia have been shown to be incredibly stress tolerant with respect
      to environmental salinity, hypoxia, and ammonia concentrations. Temperature
      challenges to this species have shown that they have difficulty with cold
      acclimation. The purpose of this study was to measure the effects of acclimation
      temperature and salinity on the thermal tolerance of Mozambique tilapia as
      assessed by critical thermal maxima (CTMax) and critical thermal minima (CTMin).
      We also monitored fish behavior and quantified ventilation rate. To our
      knowledge, this study was the first to investigate upper and lower thermal
      tolerances, and the effect of environmental salinity in this physiologically
      impressive species. Using predictive regression analyses of the thermal limits,
      thermal tolerance polygons were constructed and total areas were calculated 678.9
      degrees C2 for freshwater (FW)-acclimated tilapia, and 739.4 degrees C2 seawater
      (SW)-acclimated tilapia. During the thermal challenges, we observed two novel
      behaviors in response to thermal challenge, ventilation cessation behavior (VCB)
      and aquatic surface respiration (ASR), and we conclude that the use of these
      behaviors extended the thermal limits of these fish in both FW and two-thirds SW
      by limiting the exposure of the gill epithelium to the changing environment.

PMID- 29356425
TI  - Is there different risk of cancer among end-stage renal disease patients
      undergoing hemodialysis and peritoneal dialysis?
AB  - Cancer is a global issue in recent decade. Despite this alarming increase in the
      incidence of cancer, to date, whether the risk of developing cancer differs among
      peritoneal dialysis (PD) and hemodialysis (HD) patients is still uncertain. In
      this retrospective cohort study, data were obtained from the National Health
      Insurance Research Database of Taiwan, which provides coverage to almost 99% of
      the nation's population. After matching, a total of 4491 (or 3369) incident PD
      patients and 8982 (or 6738) incident HD patients between 2000 and 2009 were
      enrolled from the database. In addition, 22,455 (or 16,845) nondialysis patients
      were selected as a control group. The patients were monitored for the occurrence
      of cancer until 2010, and their data were analyzed using several different
      models. In general, the results showed that the risks of hepatocellular, kidney,
      bladder, extra kidney/bladder urinary tract, and thyroid cancers were higher in
      dialysis patients. We also compared the risk of cancer between two dialysis
      groups by using the HD patients as the reference group. The result showed that
      there is no significant different for each cancer risk between two dialysis
      groups. In conclusion, dialysis patients had a higher risk of certain types of
      cancer than those in the nonuremia group. However, there was no significant
      difference in the cancer risk between the two dialysis groups when compared
      directly.

PMID- 29356427
TI  - A Computational Investigation of Sources of Variability in Sentence Comprehension
      Difficulty in Aphasia.
AB  - We present a computational evaluation of three hypotheses about sources of
      deficit in sentence comprehension in aphasia: slowed processing, intermittent
      deficiency, and resource reduction. The ACT-R based Lewis and Vasishth (2005)
      model is used to implement these three proposals. Slowed processing is
      implemented as slowed execution time of parse steps; intermittent deficiency as
      increased random noise in activation of elements in memory; and resource
      reduction as reduced spreading activation. As data, we considered subject vs.
      object relative sentences, presented in a self-paced listening modality to 56
      individuals with aphasia (IWA) and 46 matched controls. The participants heard
      the sentences and carried out a picture verification task to decide on an
      interpretation of the sentence. These response accuracies are used to identify
      the best parameters (for each participant) that correspond to the three
      hypotheses mentioned above. We show that controls have more tightly clustered
      (less variable) parameter values than IWA; specifically, compared to controls,
      among IWA there are more individuals with slow parsing times, high noise, and low
      spreading activation. We find that (a) individual IWA show differential amounts
      of deficit along the three dimensions of slowed processing, intermittent
      deficiency, and resource reduction, (b) overall, there is evidence for all three
      sources of deficit playing a role, and (c) IWA have a more variable range of
      parameter values than controls. An important implication is that it may be
      meaningless to talk about sources of deficit with respect to an abstract verage
      IWA; the focus should be on the individual's differential degrees of deficit
      along different dimensions, and on understanding the causes of variability in
      deficit between participants.

PMID- 29356428
TI  - Humic acid of commercial origin causes changes in gill morphology of silver
      catfish Rhamdia quelen exposed to acidic water: Response of silver catfish gills
      to low pH and humic acid.
AB  - The effect of dissolved organic carbon (DOC) against the burden of low pH was
      assessed in silver catfish Rhamdia quelen through the gills. A commercial humic
      acid (HA) was used as the source of DOC at 0 (control), 10, 25, and 50 mg/l. For
      each HA concentration, two pH levels were tested: 6.5 (control) and 5.5. After 40
      days of exposure, the gills were removed and morphological variables were
      analyzed through light and scanning electronic microscopy. The low water pH
      caused a reduction in the length of filaments, number of lamellae, and gill
      respiratory surface area (GRSA) and an increase in chloride cells (CCs) number in
      the filament epithelium. When HA was added to the test water, GRSA increased and
      CCs proliferated in lamellae, suggesting ionic and respiratory disturbances.
      Scanning electronic microscopy revealed that CC morphometric variables, that is,
      apical area, fractional area, and density, were undisturbed by the pH reduction,
      but increased in the presence of HA. This study indicates that the commercial HA
      did not protect silver catfish against low pH stress. Instead, it caused changes
      that may affect vital processes such as ion regulation and ventilation and,
      consequently, reduce growth.

PMID- 29356429
TI  - The effects of incubation temperature and experimental design on heart rates of
      lizard embryos.
AB  - Many studies of phenotypic plasticity alter environmental conditions during
      embryonic development, yet only measure phenotypes at the neonatal stage (after
      embryonic development). However, measuring aspects of embryo physiology enhances
      our understanding of how environmental factors immediately affect embryos, which
      aids our understanding of developmental plasticity. While current research on
      reptile developmental plasticity has demonstrated that fluctuating incubation
      temperatures affect development differently than constant temperatures, most
      research on embryo physiology is still performed with constant temperature
      experiments. In this study, we noninvasively measured embryonic heart rates of
      the brown anole (Anolis sagrei), across ecologically relevant fluctuating
      temperatures. We incubated eggs under temperatures measured from potential nests
      in the field and examined how heart rates change through a diel cycle and
      throughout embryonic development. We also evaluated how experimental design
      (e.g., repeated vs. single measures designs, constant vs. fluctuating
      temperatures) and different protocols (e.g., removing eggs from incubators) might
      influence heart rate. We found that heart rates were correlated with daily
      temperature and increased through development. Our findings suggest that
      experimenters have reasonable flexibility in choosing an experimental design to
      address their questions; however, some aspects of design and protocol can
      potentially influence estimations of heart rates. Overall, we present the first
      ecologically relevant measures of anole embryonic heart rates and provide
      recommendations for experimental designs for future experiments.

PMID- 29356430
TI  - Morph-specific metabolic rate and the timing of reproductive senescence in a
      color polymorphic dragon.
AB  - Polymorphism has fascinated biologists for over a century because morphs persist
      within populations through evolutionary time in spite of showing disparate
      behavioral and physiological phenotypes; any one morph should go to fixation with
      the slightest fitness advantage over the others. Surely there must be trade-offs
      that balance selection on them. The polychromatic morphs of the Australian
      painted dragon lizard, Ctenophorus pictus, are one such system. The male color
      morphs of painted dragons have different physiological and behavioral traits
      including reproductive tactics, hormone levels, and the rate of body condition
      loss through the reproductive season. Due to their differences in physiology and
      reproductive tactics, we tested the hypotheses that male morphs would differ in
      resting metabolic rates (RMRs) and that the morphs' RMR would decline at
      different rates through the mating season. We found that bib-morphs (yellow gular
      patch) differ in RMR with bibbed (more aggressive) males having consistently
      higher RMR than non-bibbed males. Furthermore, we show that male dragons
      experience a decline in RMR as they age from reproductively active to inactive.
      We also found that the RMR of bibbed males has higher repeatability than non
      bibbed males. Our results reinforce previous hypotheses about the morph-specific
      costs of bearing a gular patch in painted dragons.

PMID- 29356431
TI  - Precision Fluorescent Labeling of an Adeno-Associated Virus Vector to Monitor the
      Viral Infection Pathway.
AB  - Adeno-associated virus 2 (AAV2) is a common vehicle for the delivery of a variety
      of therapeutic genes. A better understanding of the process of infection of AAV2
      will advance our knowledge of AAV2 biology and allow for the optimization of AAV2
      capsids with favorable transduction profiles. However, the precise fluorescent
      labeling of an AAV2 vector for probing virus tracking without affecting the
      nature of the virus remains a challenge. In this study, a lab-synthesized azide
      moieties on the viral capsid at modifiable sites is precisely displayed. Upon
      bioorthogonal copper-less click reaction, fluorophores are subsequently
      conjugated to AAV2 vectors for visualization of particles. Using this principle,
      the authors demonstrate that it can be used for visibly studying the cell entry,
      and intracellular trafficking of AAV2 particles, enabling the monitoring of the
      intracellular dynamics of AAV2 infection. This study provides new insights into
      the precision labeling of AAV2 particles with important implications for a better
      understanding of the molecular mechanism of therapeutic gene delivery.

PMID- 29356432
TI  - Interactive effects of algal level and predator density (Asplanchna sieboldi) on
      the life-history strategy and morphology of Brachionus calyciflorus.
AB  - Predation plays an important role in mediating the coexistence and the community
      structure of rotifera. In response to predation stresses, prey rotifers develop
      morphological defenses and change their life-history strategy for the
      reallocation of energy investment. Yet, how these changes respond to different
      total energy ingestion remains largely unknown. In the present study, we
      investigated the life-table demographic, population growth and morphological
      parameters of Brachionus calyciflorus in response to various densities of
      Asplanchna sieboldi at two food levels (1.0  *  106 and 2.0  *  106 cells per ml
      of Scenedesmus obliquus). To resist predators, B. calyciflorus developed long
      postero-lateral spines. The life-table demographic results showed that predation
      only significantly shortened the generation time of B. calyciflorus at the algal
      level of 2.0  *  106 cells per ml, but not affect other demographic parameters.
      The population growth tests revealed that predator density, algal level and their
      interactions all significantly influenced the population growth rate of prey
      rotifers. At 1.0  *  106 cells per ml of S. obliquus, treatments with two, four,
      and eight A. sieboldi individuals per 50 ml significantly reduced the population
      growth rate of B. calyciflorus. In contrast, the population growth rate was not
      affected in response to two A. sieboldi individuals per 50 ml at 2.0  *  106
      cells per ml of S. obliquus. These results suggested that algal level probably
      affected the inhibitory effects of predation on the population growth of prey
      rotifers, and the underlying mechanisms should be further investigated.

PMID- 29356433
TI  - Cardiopulmonary exercise test to quantify enzyme replacement response in
      pediatric Pompe disease.
AB  - INTRODUCTION: Enzyme replacement therapy (ERT) with Myozyme improved the prospect
      of Pompe disease patients. Our aim was to evaluate ERT acute effect on exercise
      capacity in pediatric Pompe patients. METHODS: Five Pompe patients (10-19 years,
      4 infantile-onset and 1 diagnosed at 5 years) were evaluated before and 2 days
      after ERT using cardiopulmonary exercise testing (CPET), 6 min walking test
      (6MWT) and motor function test (GMFM-88). RESULTS: Preserved normal peak oxygen
      uptake, 6MWT and motor function were observed in the relative mild disease and
      impairment of these parameters in the more advanced disease. Two days following
      ERT, three patients demonstrated changes; one patient (relative mild disease)
      increased both oxygen uptake (11%) and walking distance (38%). Second patient
      (advanced disease) increased oxygen uptake (11%) while a small decrease in
      walking distance in the 6MWT (8%) was observed. Third patient (advanced disease)
      decreased oxygen uptake (39%) but increased walking distance (42%) and motor
      function score (27%). CONCLUSIONS: CPET is safe for pediatric Pompe patients. ERT
      may benefit exercise capacity in patients with less advanced disease.
      Individualized assessment by CPET, 6MWT, and motor function may help ERT
      adjustment by providing precise quantification of the response to treatment.
      Additional studies are needed to clarify the benefit of this assessment protocol.

PMID- 29356434
TI  - 5-Chloro-2,4-dihydroxypyridine, CDHP, prevents lung metastasis of basal-like
      breast cancer cells by reducing nascent adhesion formation.
AB  - A drug for metastasis prevention is necessary. The orally administered anticancer
      drug S-1 contributes to cancer therapy. In a mouse xenograft model of metastatic
      breast cancer from our previous study, the administration of S-1 inhibited lung
      metastasis. However, the mechanism of inhibition remains elusive. S-1 contains 5
      chloro-2,4-dihydroxypyridine (CDHP), which does not have the antigrowth activity,
      but prevents the degradation of 5-fluorouracil, an anticancer reagent. In this
      study, we found that CDHP treatment shrinks cell morphology in metastatic basal
      like breast cancer cell lines. Wound healing assays showed reduced cell migration
      in CDHP-treated cells. At the molecular level, CDHP treatment reduced the number
      of nascent adhesions, whereas the number of mature focal adhesions was not
      changed. These findings indicate that CDHP impairs focal adhesion formation,
      which results in a reduction in cell migration. For the in vivo metastasis assay,
      we used a highly lung-metastatic cell line. We xenografted them into
      immunodeficient mice, and administered CDHP. To determine whether CDHP prevents
      metastasis, we measured the weights of harvested lungs. The results showed that
      the lung weights of the CDHP-treated animals were not significantly different
      compared to the no-tumor controls, whereas the vehicle group showed a number of
      metastatic foci and an increase in lung weight. These observations indicate that
      CDHP administration prevents metastasis. This study reveals a novel effect of
      CDHP for lung metastasis prevention. Our findings may facilitate the
      establishment of future metastasis prevention therapies.

PMID- 29356435
TI  - Correlates of melanization in multiple high- and low-elevation populations of the
      lizard, Sceloporus occidentalis: Behavior, hormones, and parasites.
AB  - Hormones mediate the expression of suites of correlated traits and hence may act
      either to facilitate or constrain adaptive evolution. Selection on one trait
      within a hormone-mediated suite of traits may lead to a change in the strength of
      the hormone signal, causing changes in correlated traits. Growing evidence
      suggests that melanization, which is in part regulated by hormonal signals, is
      tightly linked to other traits, such as aggression and stress physiology. Here,
      we examine six populations of Sceloporus occidentalis lizards differing in degree
      of melanization (three dark higher-elevation populations and three less-melanized
      lower-elevation populations) to investigate potential correlations between
      behavior, hormones, and parasites. We measured aggression by recording behavioral
      responses of males to staged territorial intrusions; behavior was summarized by
      two principal components. Analysis revealed that males in the three darker
      populations signaled aggression less often and made more physical contact than
      males in the lighter populations. Analyses of plasma steroid hormones
      (corticosterone and testosterone) revealed significant population differences,
      but counter to expectation higher aggression was associated with lower
      testosterone compared across populations. Finally, the three darker populations
      had higher mean mite loads than the three lighter populations. Overall, this
      array of phenotypic correlations does not parallel patterns of within-population
      differences in melanization found in other vertebrates, suggesting that hormonal
      correlations do not constrain phenotype variation across populations in this
      species. Given this contradiction between population- and individual-level
      variation, we urge more study at both levels of variation in traits potentially
      associated with melanization in other vertebrates.

PMID- 29356436
TI  - Health insurance and use of recommended routine care in adults with cystic
      fibrosis.
AB  - BACKGROUND: Low socioeconomic status is correlated with worse outcomes in
      patients with cystic fibrosis (CF). Whether insurance status impacts adherence to
      care in this population is unknown. METHODS: Patients >=18 years old in the CF
      Foundation Patient Registry (2005-2013) were grouped based on reported annual
      insurance as private, public (Medicaid, Medicare or state medical assistance
      program), others or no insurance. Random effects logistic regression evaluated
      association between change in insurance status and annual use of recommended
      routine care. RESULTS: A total of 18 358 patients contributed 94 690 years of
      data to the analysis. In descriptive analysis, adherence to recommended routine
      care (>=4 clinic visits, >=4 respiratory cultures and >=2 pulmonary function
      tests per year) and recommended chronic medications for those with moderate to
      severe lung disease (dornase alfa and inhaled tobramycin or aztreonam if
      Pseudomoas aeruginosa in respiratory cultures) was most common in public
      insurance compared to other insurance types. In multivariable logistic
      regression, public insurance was associated with greater use of recommended care
      relative to private insurance (OR = 1.16; 95% confidence interval: 1.10-1.22; P <
      .001), while being uninsured was associated with lower odds of using recommended
      care (OR = 0.37; 95% confidence interval: 0.31-0.46; P < .001). CONCLUSIONS: For
      adults with CF in the United States, public insurance was associated with greater
      use of routine care than private coverage. Being uninsured was strongly
      associated with not using routine care. Further efforts to improve access to CF
      care should address the feasibility of universal and continuous insurance
      coverage in the CF population.

PMID- 29356437
TI  - Interventions to improve retention in a surgical, clinical trial: A pragmatic,
      stakeholder-driven approach.
AB  - OBJECTIVE: To explore stakeholder perspectives upon participant retention in
      clinical trials, and to generate strategies to support retention in a surgical,
      clinical trial. STUDY DESIGN AND SETTING: The SWIFFT trial is a multicenter study
      comparing treatments for the fracture of the waist of the scaphoid bone in
      adults. Here we report upon a multistage, iterative consultative process with
      SWIFFT stakeholders, these include workshops with members of the public, with
      nurses involved in data collection, and with consultant clinicians. Structured
      discussions were digitally recorded and transcribed, data were handled and
      analyzed following a framework approach to qualitative data analysis. RESULTS:
      Removing practical barriers were identified as important factors in supporting
      retention. Stakeholders also identified that (i) how well a study is understood
      and (ii) how much it is valued are important factors in an individual's
      willingness to maintain their involvement. A number of strategies resulted from
      this consultation, these include: in-clinic data collection, co-ordinated
      clinical and research appointments, a SWIFFT website, and newsletter. CONCLUSION:
      A participatory approach to trial retention might engage all relevant
      stakeholders in the delivery of a clinical trial, it might also support the
      generation of specific and contextually relevant solutions to the challenge of
      participant retention.

PMID- 29356438
TI  - Impact of tobacco, alcohol and cannabis use on treatment outcomes among patients
      experiencing first episode psychosis: Data from the national RAISE-ETP study.
AB  - AIM: The primary aim of this study was to examine the effect of recent tobacco,
      alcohol and cannabis use on treatment outcomes among participants experiencing
      first episode psychosis (FEP). METHODS: Secondary data analyses were conducted on
      404 participants enrolled in the Recovery After an Initial Schizophrenia Episode
      Early Treatment Program (RAISE-ETP) study. RAISE-ETP investigated the
      effectiveness of a coordinated specialty care (CSC) intervention for FEP in
      community mental health agencies in the United States. Generalized estimating
      equations were used to examine whether recent tobacco smoking, alcohol, and
      cannabis use at baseline were associated with illness severity, number of
      antipsychotic pills missed, psychiatric symptoms and quality of life during the
      24-month treatment period, after controlling for duration of untreated psychosis
      and treatment group. RESULTS: At baseline, roughly 50% (n = 209) of participants
      reported recent tobacco, 28% (n = 113) alcohol and 24% (n = 95) cannabis use.
      Tobacco smokers had higher levels of illness severity (beta = .24; P < .005), a
      higher number of missed pills (beta = 2.89; P < .05), higher psychiatric symptoms
      and lower quality of life during treatment relative to non-smokers. Alcohol users
      had a higher number of missed pills (beta = 3.16; P < .05) during treatment and
      cannabis users had higher levels of illness severity (beta = .18; P < .05) and
      positive symptoms (beta = 1.56; P < .05) relative to non-users. CONCLUSIONS:
      Tobacco, alcohol and cannabis use are common in youth seeking treatment for FEP.
      Tobacco smoking was associated with more negative clinical outcomes. These
      findings have implications for including interventions targeting these areas of
      substance use within current CSC models.

PMID- 29356439
TI  - Relationships between parasitic infection and natural antibodies, age, and sex in
      a long-lived vertebrate.
AB  - Reptilian immune systems are believed to rely more heavily on the innate response
      than the adaptive response. Past research on reptilian immune systems has
      indicated that natural antibodies (NAbs) play an important role in fighting
      antigens as the first responder and initiating the innate immune response.
      However, there is a gap in research on NAbs in reptiles as there is little data
      on how they may influence parasite prevalence in reptiles. Furthermore, no
      studies have examined NAbs at mucosal sites, which represent an important point
      of entry for parasites. We investigated NAbs in male and female red-eared slider
      turtles (Trachemys scripta) in order to begin to fill this gap in our
      understanding. Plasma and mucosal samples were collected from T. scripta to
      determine total immunoglobulin levels in relation to intestinal parasite load,
      which was determined from fecal samples. We also determined antibody levels to
      various antigens to examine if NAbs are present in mucosal samples and how levels
      compare to plasma NAbs. In female turtles, parasite intensity decreased with
      increasing host age and mucosal antibody levels. We also found that the levels of
      antibodies that bind to a novel antigen and an antigen they are likely to have
      encountered were significantly related in both plasma and mucosal samples,
      indicating a NAb response. This study contributes to our understanding of how
      reptiles may rely on a broad innate response that allows them to resist potential
      pathogens while potentially avoiding some negative consequences of
      immunosenescence.

PMID- 29356440
TI  - Adherence and medication belief in patients with pulmonary arterial hypertension
      or chronic thromboembolic pulmonary hypertension: A nationwide population-based
      cohort survey.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) and chronic thromboembolic
      pulmonary hypertension (CTEPH) are rare diseases with a gradual decline in
      physical health. Adherence to treatment is crucial in these very symptomatic and
      life threatening diseases. OBJECTIVE: To describe PAH and CTEPH patients
      experience of their self-reported medication adherence, beliefs about medicines
      and information about treatment. METHODS: A quantitative, descriptive, national
      cohort survey that included adult patients from all PAH-centres in Sweden. All
      patients received questionnaires by mail: The Morisky Medication Adherence Scale
      (MMAS-8) assesses treatment-related attitudes and behaviour problems, the Beliefs
      about Medicines Questionnaire-Specific scale (BMQ-S) assesses the patient's
      perception of drug intake and the QLQ-INFO25 multi-item scale about medical
      treatment information. RESULTS: The response rate was 74% (n = 325), mean age 66
      +/- 14 years, 58% were female and 69% were diagnosed with PAH and 31% with CTEPH.
      Time from diagnosis was 4.7 +/- 4.2 years. More than half of the patients (57%)
      reported a high level of adherence. There was no difference in the patients'
      beliefs of the necessity of the medications to control their illness when
      comparing those with high, medium or low adherence. Despite high satisfaction
      with the information, concerns about potential adverse effects of taking the
      medication were significantly related to adherence. CONCLUSIONS: Treatment
      adherence is relatively high but still needs improvement. The multi-disciplinary
      PAH team should, together with the patient, seek strategies to improve adherence
      and prevent concern.

PMID- 29356441
TI  - Parent and clinician agreement regarding early behavioral signs in 12- and 18
      month-old infants at-risk of autism spectrum disorder.
AB  - : Parent and clinician agreement regarding early behavioral signs of Autism
      Spectrum Disorder (ASD) in children from a high-risk cohort (siblings of children
      diagnosed with ASD, n = 188) was examined. Infants were assessed prospectively at
      12 and 18 months of age using the clinician administered Autism Observational
      Scale for Infants (AOSI) and the Autism Parent Screen for Infants (APSI) and
      underwent a blind independent diagnostic assessment for ASD at 36 months of age.
      Direct comparison of parent and clinician ratings showed poor agreement on all
      early behavioral signs, with parent-reported symptoms being better able to
      differentiate between children with and without ASD at both 12 and 18 months of
      age compared to clinician observations during a brief office visit. The results
      suggest that parents may detect some clinically informative behaviors based on
      their day-to-day observations more readily than do clinicians during brief
      clinical assessments, a result that needs to be replicated in a non-sibling
      cohort. Autism Res 2018, 11: 539-547. (c) 2018 International Society for Autism
      Research, Wiley Periodicals, Inc. LAY SUMMARY: Parents of children at high-risk
      of autism spectrum disorder (ASD; have an older sibling with ASD) and clinicians
      were compared on their reporting of 19 early signs of autism. Direct comparison
      of parent and clinician ratings showed poor agreement on all early behavioral
      signs, with parent-reported symptoms being better able to differentiate between
      children with and without ASD at both 12 and 18 months of age compared to
      clinician observations during a brief office visit. This suggests that parents
      may have important information regarding early development of their high-risk
      child.

PMID- 29356442
TI  - Detrimental interactions of neonicotinoid pesticide exposure and bumblebee
      immunity.
AB  - Pesticides are well known to have a number of ecological effects. However, it is
      only now becoming understood that sublethal exposures may have effects on
      nontarget insects of conservation concern through interactions with immunity,
      thus increasing detrimental impacts in the presence of pathogens. Pesticides and
      pathogens are suggested to have played a role in recent declines of several wild
      bee pollinators. Compromised immunity from exposure to widely used neonicotinoids
      has been demonstrated in honeybees, but further research on interactions between
      neonicotinoids and immunity in other important bees is lacking. In this study,
      adult workers of the bumblebee Bombus impatiens received 6-day pulses of either
      low (0.7 ppb) or high (7 ppb) field realistic doses of the neonicotinoid
      imidacloprid prior to assaying immunity and survival following a nonpathogenic
      immune challenge. High-dose imidacloprid exposure reduces constitutive levels of
      phenoloxidase, an enzyme involved in melanization. Hemolymph antimicrobial
      activity initially increases in all groups following an immune challenge, but
      while heightened activity is maintained in unexposed and low imidacloprid dose
      groups, it is not maintained in the high exposure dose bees, even though exposure
      had ceased 6 days prior. Additionally, imidacloprid exposure followed by an
      immune challenge significantly decreased survival probability relative to control
      bees and those only immune challenged or imidacloprid exposed. A temporal lag for
      immune modulation and combinatorial effects on survival suggest that resource
      based trade-offs may, in part, contribute to the detrimental interactions. These
      interactions could have health consequences for pollinators facing multiple
      stresses of sublethal neonicotinoid exposure and pathogens.

PMID- 29356443
TI  - Immune profiles vary seasonally, but are not significantly related to migration
      distance or natal dispersal, in a migratory songbird.
AB  - A central tenet of ecoimmunology is that an organism's environment shapes its
      optimal investment in immunity. For example, the benefits of acquired (relatively
      pathogen specific) versus innate (nonspecific) immune defenses are thought to
      vary with the risk of encountering familiar versus unfamiliar pathogens. Because
      pathogen communities vary geographically, individuals that travel farther during
      seasonal migration or natal dispersal are predicted to have higher exposure to
      novel pathogens, and lower exposure to familiar pathogens, potentially favoring
      investment in innate immunity. During the breeding season, migratory animals'
      exposure to familiar pathogens should increase, potentially favoring investment
      in acquired immunity. We hypothesized that song sparrows Melospiza melodia adjust
      their constitutive immune profiles in response to risk of encountering novel
      versus familiar pathogens. We predicted that individuals migrating longer
      distances (inferred from stable hydrogen isotope analysis of claws) and less
      philopatric individuals (inferred from microsatellite assignment testing) would
      rely more heavily on acquired than innate defenses. We also predicted that
      reliance on acquired defenses would increase throughout the early breeding
      season. Consistent with trade-offs between acquired and innate defenses, levels
      of immunoglobulin Y (acquired) varied negatively with macrophage phagocytosis
      activity (innate). Levels of acquired relative to innate immunity did not vary
      significantly with migration distance or philopatry, but increased throughout the
      early breeding season. Macrophage phagocytosis was not significantly repeatable
      between years. Song sparrows appear to shift from innate defenses immediately
      after migration to acquired defenses with increasing time at the breeding
      grounds. These patterns highlight the plasticity of constitutive immune defenses
      in migratory animals.

PMID- 29356444
TI  - Physiological plasticity in lizard embryos exposed to high-altitude hypoxia.
AB  - Coping with novel environments may be facilitated by plastic physiological
      responses that enable survival during environmentally sensitive life stages. We
      tested the capacity for embryos of the common wall lizard (Podarcis muralis) from
      low altitude to cope with low-oxygen partial pressure (hypoxia) in an alpine
      environment. Developing embryos subjected to hypoxic atmospheric conditions (15
      16% O2 sea-level equivalent) at 2,877 m above sea level exhibited responses
      common to vertebrates acclimatized to or evolutionarily adapted to high altitude:
      suppressed metabolism, cardiac hypertrophy, and hyperventilation. These responses
      might have contributed to the unaltered incubation duration and hatching success
      relative to the ancestral, low-altitude, condition. Even so, hypoxia constrained
      egg energy utilization such that larger eggs produced hatchlings with relatively
      low mass. These findings highlight the role of physiological plasticity in
      maintaining fitness-relevant phenotypes in high-altitude environments, providing
      impetus to further explore altitudinal limits to ecological diversification in
      ectothermic vertebrates.

PMID- 29356445
TI  - Chronic repeated exposure to weather-related stimuli elicits few symptoms of
      chronic stress in captive molting and non-molting European starlings (Sturnus
      vulgaris).
AB  - Repeated exposure to acute stressors causes dramatic changes in an animal's
      stress physiology and the cumulative effects are often called chronic stress.
      Recently we showed that short-term exposure to weather-related stimuli, such as
      temperature change, artificial precipitation, and food restriction, cause acute
      responses in captive European starlings (Sturnus vulgaris). Here, we examined the
      effect of repeated exposure to weather-related stressors on heart rate and
      corticosterone (CORT) of captive non-molting and molting European starlings. Four
      times every day for 3 weeks, birds were exposed to either 30 min of a subtle (3
      degrees C) decrease in temperature, a short bout of simulated rain, or 2 hr of
      food removal. The order and time of presentation were randomly assigned on each
      day. We found no differences in heart rate or heart rate variability.
      Furthermore, there were no changes in baseline CORT levels, CORT negative
      feedback efficacy, or maximal adrenal capacity. Mass increased across the
      experimental period only in molting birds. CORT responses to restraint were
      decreased in both groups following treatment, suggesting the birds had
      downregulated their responses to acute stress. Molting birds showed evidence of
      suppression of the HPA axis compared with non-molting birds, which is consistent
      with previous research. Overall, our data show that repeated exposure to weather
      related stressors does not elicit most of the symptoms normally associated with
      chronic stress.

PMID- 29356446
TI  - Local and systemic immune responses to different types of phytohemagglutinin in
      the green anole: Lessons for field ecoimmunologists.
AB  - The phytohemagglutinin (PHA) skin test is commonly used by ecologists to assess
      cell-mediated immune function of wild animals. It can be performed quickly and
      easily in the field, involving injection of PHA and measurement of the resultant
      swelling. There are multiple formulations of PHA used in ecological studies, with
      potentially differing outcomes that could produce inconsistent results. We tested
      two common types of PHA in the green anole (Anolis carolinensis) to identify
      local and systemic immune responses underlying the resultant swelling at 6, 18,
      24, and 48 hr post injection. There were differences in both local (injection
      site) and systemic (blood) leukocyte responses to PHA-L versus PHA-P. PHA-P
      injection produced a greater overall increase in local heterophil count at the
      injection site compared with PHA-L, and this response was greatest at 6 and 24 hr
      post injection. Systemically, heterophil percentage was higher in the blood of
      PHA-P- versus PHA-L-injected anoles at 24 hr post injection; the time point at
      which heterophil percentage peaked in PHA-P-injected anoles. These results
      indicate that although both PHA types are effective tests of immune function in
      green anoles, the PHA-P swelling response invokes a much stronger heterophilic
      response. PHA-L is a more specific test of lymphocyte function, particularly at
      24 hr post injection, making it preferable for ecoimmunology studies.

PMID- 29356447
TI  - The full-length sequence of the HLA-C allele, HLA-C*03:40:01.
AB  - Confirmed the full-length sequence of HLA-C*03:40:01 by cloning and sequencing in
      a Chinese donor.

PMID- 29356448
TI  - Distribution and concentration of maternal progesterone in the yolk of Greater
      Rhea eggs (Rhea americana).
AB  - Progesterone is the most concentrated maternal yolk steroid characterized to date
      in birds; however, no information about it is available in ratite eggs. We
      collected freshly laid eggs from zoo-housed Greater Rhea females (Rhea americana)
      bred under similar rearing conditions during two breeding seasons to characterize
      concentration and distribution of maternal yolk progesterone. After high
      performance liquid chromatography analysis, yolk hormone was measured using a
      commercial electrochemiluminescence immunoassay. Progesterone concentrations were
      found to vary significantly among the yolk layers, supporting a follicular origin
      for this steroid in Greater Rhea eggs. Additionally, highly similar mean absolute
      yolk progesterone concentrations were detected between 2013 and 2015 breeding
      seasons (1,332.98 +/- 82.59 and 1,313.59 +/- 85.19 ng/g, respectively). These
      values are also comparable to those found in some domestic carinate species.
      Findings suggest that at population level, when rearing conditions are similar,
      mean absolute yolk maternal progesterone concentrations also appear bounded.
      Future research on the factors and mechanisms that regulate progesterone
      deposition in Greater Rhea eggs is needed to better understand whether its levels
      depend on different rearing conditions.

PMID- 29356449
TI  - Ectoparasites as developmental stressors: Effects on somatic and physiological
      development.
AB  - Developmental stress can alter resource allocation in early life, and in
      altricial birds with rapid developmental trajectories and high resource demands,
      nestlings may adjust early resource partitioning to cope with challenging
      environments. We experimentally manipulated ectoparasite levels in nests and
      assessed whether ectoparasites affected somatic and physiological development in
      European starling (Sturnus vulgaris) nestlings. We hypothesized that mites act as
      developmental stressors in nestlings and predicted that nestlings from infested
      nests would exhibit either reduced somatic growth, or reduced physiological
      development, including impaired innate immunity, and would have elevated
      corticosterone concentrations. We either added ~200 mites to nests during early
      incubation, or treated nests with a pesticide, permethrin, to reduce mites and
      possibly other arthropods. We assessed treatment effects on egg spottiness and
      mite abundance, and monitored offspring hatching and survival. We also measured
      somatic growth (mass, tarsus length, and feather growth), hematocrit, immune
      related metrics (bacterial killing ability [BKA] and spleen mass), and baseline
      corticosterone concentrations in response to treatment. Compared with mite
      treatment, permethrin reduced egg spottiness and mite abundance in nests.
      Relative to nestlings in mite-reduced nests, nestlings in mite-enhanced nests had
      lower survival, hematocrit, and corticosterone concentrations. Early in
      development, nestlings from both treatments exhibited similar rapid somatic
      growth, yet mite-treated nestlings exhibited lower BKA. Nestlings in both
      treatments increased BKA across development, despite nestlings in mite-treated
      nests exhibiting lower mass as nest leaving neared. Overall, we found evidence
      that mites can act as development stressors, but contrary to our prediction,
      mites decreased corticosterone concentrations.

PMID- 29356450
TI  - A prospective study of fetal head growth, autistic traits and autism spectrum
      disorder.
AB  - : Altered trajectories of brain growth are often reported in Autism Spectrum
      Disorder (ASD), particularly during the first year of life. However, less is
      known about prenatal head growth trajectories, and no study has examined the
      relation with postnatal autistic symptom severity. The current study
      prospectively examined the association between fetal head growth and the spectrum
      of autistic symptom severity in two large population-based cohorts, including a
      sample of individuals with clinically diagnosed ASD. This study included 3,820
      children from two longitudinal prenatal cohorts in The Netherlands and Australia,
      comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve
      models were used to examine the relationship between fetal head circumference
      measured at three different time points and autistic traits measured in postnatal
      life using either the Social Responsiveness Scale or the Autism-Spectrum
      Quotient. While lower initial prenatal HC was weakly associated with increasing
      autistic traits in the Dutch cohort, this relationship was not observed in the
      Australian cohort, nor when the two cohorts were analysed together. No
      differences in prenatal head growth were found between individuals with ASD and
      controls. This large population-based study identified no consistent association
      across two cohorts between prenatal head growth and postnatal autistic traits.
      Our mixed findings suggest that further research in this area is needed. Autism
      Res 2018, 11: 602-612. (c) 2018 The Authors Autism Research published by
      International Society for Autism Research and Wiley Periodicals, Inc. LAY
      SUMMARY: It is not known whether different patterns of postnatal brain growth in
      Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head
      growth and autistic symptoms in two large groups from The Netherlands and
      Australia. Lower initial prenatal head circumference was associated with autistic
      traits in the Dutch, but not the Australian, group. No differences in head growth
      were found in individuals with ASD and controls when the data was combined. Our
      mixed findings suggest that more research in this area is needed.

PMID- 29356452
TI  - A gross anatomy flipped classroom effects performance, retention, and higher
      level thinking in lower performing students.
AB  - A flipped classroom is a growing pedagogy in higher education. Many research
      studies on the flipped classroom have focused on student outcomes, with the
      results being positive or inconclusive. A few studies have analyzed confounding
      variables, such as student's previous achievement, or the impact of a flipped
      classroom on long-term retention and knowledge transfer. In the present study,
      students in a Doctor of Physical Therapy program in a traditional style lecture
      of gross anatomy (n = 105) were compared to similar students in a flipped
      classroom (n = 112). Overall, students in the flipped anatomy classroom had an
      increase in semester average grades (P = 0.01) and performance on higher-level
      analytical questions (P < 0.001). Long-term retention and knowledge transfer was
      analyzed in a subsequent semester's sequenced kinesiology course, with students
      from the flipped anatomy classroom performing at a higher level in kinesiology (P
      < 0.05). Student's pre-matriculation grade point average was also considered.
      Previously lower performing students, when in a flipped anatomy class,
      outperformed their traditional anatomy class counterparts in anatomy semester
      grades (P < 0.05), accuracy on higher-level analytical anatomy multiple-choice
      questions (P < 0.05) and performance in subsequent course of kinesiology (P <
      0.05). This study suggests that the flipped classroom may benefit lower
      performing student's knowledge acquisition and transfer to a greater degree than
      higher performing students. Future studies should explore the underlying reasons
      for improvement in lower performing students.

PMID- 29356451
TI  - Gene encoding the CTP synthetase as an appropriate molecular tool for
      identification and phylogenetic study of the family Bifidobacteriaceae.
AB  - An alternative molecular marker with respect to the 16S rRNA gene demonstrating
      better identification and phylogenetic parameters has not been designed for the
      whole Bifidobacteriaceae family, which includes the genus Bifidobacterium and
      scardovial genera. Therefore, the aim of the study was to find such a gene in
      available genomic sequences, suggest appropriate means and conditions for
      asmplification and sequencing of the desired region of the selected gene in
      various strains of the bacterial family and verify the importance in
      classification and phylogeny. Specific primers flanking the variable region (~800
      pb) within the pyrG gene encoding the CTP synthetase were designed by means of
      gene sequences retrieved from the genomes of strains belonging to the family
      Bifidobacteriaceae. The functionality and specificity of the primers were
      subsequently tested on the wild (7) and type strains of bifidobacteria (36) and
      scardovia (7). Comparative and phylogenetic studies based on obtained sequences
      revealed actual significance in classification and phylogeny of the
      Bifidobacteriaceae family. Gene statistics (percentages of mean sequence
      similarities and identical sites, mean number of nucleotide differences, P- and K
      distances) and phylogenetic analyses (congruence between tree topologies,
      percentages of bootstrap values >50 and 70%) indicate that the pyrG gene
      represents an alternative identification and phylogenetic marker exhibiting
      higher discriminatory power among strains, (sub)species, and genera than the 16S
      rRNA gene. Sequences of the particular gene fragment, simply achieved through
      specific primers, enable more precisely to classify and evaluate phylogeny of the
      family Bifidobacteriaceae including, with some exceptions, health-promoting
      probiotic bacteria.

PMID- 29356453
TI  - Association between 1p13 polymorphisms and peripheral arterial disease in a
      Chinese population with diabetes.
AB  - AIMS/INTRODUCTION: Variants on chromosome 1p13 have been associated with coronary
      artery disease and acute myocardial infarction risk in different ethnic groups.
      The present study aimed to investigate the association between 1p13 polymorphisms
      and the development of peripheral artery disease (PAD) in a Chinese population
      with type 2 diabetes mellitus. MATERIALS AND METHODS: 1p13 polymorphisms,
      rs599839, rs646776 and rs12740374, were assessed in a cohort of 882 type 2
      diabetes mellitus patients including 440 type 2 diabetes mellitus patients with
      PAD (DM + PAD group) and 442 patients without PAD (DM group). Genotyping was
      carried out using TaqMan assay. RESULTS: Compared with the DM group, the
      frequencies of the minor G allele of both rs599839 and rs646776 and the minor T
      allele of rs12740374 decreased (P = 0.013, P = 0.019 and P = 0.005,
      respectively), and the frequencies of rs599839 AG + GG, rs646776 AG + GG and
      rs12740374 CT+TT genotypes were statistically significantly decreased as well (P
      = 0.017, P = 0.011 and P = 0.007, respectively) in the dominant model in the DM +
      PAD group than in the DM group. Multivariate unconditional logistic regression
      analyses adjusted for age, glycated hemoglobin, triglyceride, low-density
      lipoprotein cholesterol, smoking, hypertension, diabetes duration, coronary heart
      disease and cerebral infarction showed that the genotypic distribution of
      rs599839 AG + GG, rs646776 AG + GG and rs12740374 CT + TT remained statistically
      different between the DM and DM + PAD group (P = 0.014, P = 0.003 and P = 0.004,
      respectively). The frequencies of haplotype GGT were statistically significantly
      different between groups (P = 0.08). CONCLUSIONS: The present study strongly
      supports that genotypes of rs599839, rs646776 and rs12740374 on 1p13 are
      protective factors for diabetic PAD in a Chinese population. Haplotype GGT
      generated by rs599839, rs646776 and rs12740374 might also decrease the risk of
      the disease.

PMID- 29356454
TI  - Correlates of immune defenses in golden eagle nestlings.
AB  - An individual's investment in constitutive immune defenses depends on both
      intrinsic and extrinsic factors. We examined how Leucocytozoon parasite presence,
      body condition (scaled mass), heterophil-to-lymphocyte (H:L) ratio, sex, and age
      affected immune defenses in golden eagle (Aquila chrysaetos) nestlings from three
      regions: California, Oregon, and Idaho. We quantified hemolytic-complement
      activity and bacterial killing ability, two measures of constitutive immunity.
      Body condition and age did not affect immune defenses. However, eagles with lower
      H:L ratios had lower complement activity, corroborating other findings that
      animals in better condition sometimes invest less in constitutive immunity. In
      addition, eagles with Leucocytozoon infections had higher concentrations of
      circulating complement proteins but not elevated opsonizing proteins for all
      microbes, and eagles from Oregon had significantly higher constitutive immunity
      than those from California or Idaho. We posit that Oregon eagles might have
      elevated immune defenses because they are exposed to more endoparasites than
      eagles from California or Idaho, and our results confirmed that the OR region has
      the highest rate of Leucocytozoon infections. Our study examined immune function
      in a free-living, long-lived raptor species, whereas most avian ecoimmunological
      research focuses on passerines. Thus, our research informs a broad perspective
      regarding the evolutionary and environmental pressures on immune function in
      birds.

PMID- 29356455
TI  - Low salinity-induced alterations in epithelial ultrastructure, Na+/K+-ATPase
      immunolocalization and enzyme kinetic characteristics in the gills of the
      thinstripe hermit crab, Clibanarius vittatus (Anomura, Diogenidae).
AB  - Fresh caught Clibanarius vittatus [SW, 310/00 salinity (S)] were acclimated to a
      dilute medium (150/00 S) for 10 days, employing silver staining to locate gill
      ion transporting tissue, immunofluorescence to localize the Na+/K+-ATPase alpha
      subunit in the lamellae, and electron microscopy to portray ultrastructural
      changes in the gill epithelia. Na+/K+-ATPase activity was characterized
      kinetically in a gill microsomal fraction, including synergistic stimulation by
      NH4+ plus K+. Silver staining revealed that all 26 phyllobranchiate arthro- and
      pleurobranchiae participate in ion transport. Na+/K+-ATPase alpha-subunit
      staining was weak in SW crabs and distributed exclusively and irregularly within
      the intralamellar septal cells, particularly at the septal-pillar cell body
      junctions, and septal cell cytoplasm facing the hemolymph space. In 150/00 S
      crabs, alpha-subunit localization was intense, occupying the entire thickened
      septum. Pillar cells and flanges did not stain. Mitochondria and membrane
      foldings increased in the pillar cell flanges and intralamellar septal cells,
      greatly amplifying surface area. Only a single ATP binding site (VM  =  130.8 +/-
      10.5 nmol min-1 mg protein-1; K0.5  =  55.3 +/- 1.7 MUmol l-1) obeying Michaelis
      Menten kinetics was disclosed. Na+/K+-ATPase activity was modulated by Mg2+, Na+,
      and NH4+, exhibiting site-site interactions; K+ modulation showed Michaelis
      Menten kinetics. K+ plus NH4+ synergistically stimulated activity ~ 1.7-fold.
      Ouabain inhibited total ATPase activity by ~ 70% (KI  =  220-300 MUmol l-1),
      revealing phosphohydrolytic activities other than the Na+/K+-ATPase. Despite
      ample phylogenetic separation, the phyllobranchiate lamellae of the Anomura and
      Caridea share many ultrastructural features, that is, an intralamellar septum and
      opposed abutting pillar cells, similar Na+/K+-ATPase distribution, and comparable
      kinetic characteristics. These findings suggest either convergent evolution at
      the structural and biochemical levels, or preservation of traits present in a
      remote common ancestor.

PMID- 29356456
TI  - Mechanisms underlying maternal care in a viviparous snake, Sistrurus miliarius:
      Does maternal body condition, corticosterone, or arginine vasotocin mediate post
      birth maternal investment?
AB  - The level of parental investment in free-living offspring varies greatly within
      and among vertebrate taxa, and the mechanisms that mediate investment are likely
      targets of selection in the evolution of reproductive strategies. In mammalian
      and avian systems, individual investment is adjusted according to parental
      energetic status, and regulatory mechanisms have been described. Parental care is
      also a component of the life history of several groups of squamates and
      archosaurs, but little to nothing is known regarding the mechanisms that underlie
      individual variation in parental investment in these groups. Therefore, we
      examined the relationships among maternal body condition, corticosterone,
      arginine vasotocin (AVT), and maternal care in postparturient pigmy rattlesnakes.
      Energetic status was manipulated in pregnant females by supplemental feeding, and
      AVT was manipulated in postparturient mothers by intraperitoneal injection.
      Circulating corticosterone and body condition were recorded in postparturient
      mothers. Mother-offspring spatial relationships were analyzed to determine the
      closeness of mother-offspring associations. No significant relationship between
      maternal body condition and baseline corticosterone was observed in mothers, and
      no significant relationship was found between corticosterone and the level of
      maternal association with offspring. Manipulation of AVT did not stimulate
      maternal care. There was a strong and repeatable positive relationship between
      maternal postparturient body condition and the level of maternal association with
      offspring. The lack of a significant correlation between body condition and
      corticosterone does not support the hypothesis that a postparturient
      glucocorticoid response drives the observed condition-dependence of maternal
      offspring association.

PMID- 29356457
TI  - Seasonal variation and correlation between corticosterone and the antioxidant
      uric acid during stress in the Northern Cardinal (Cardinalis cardinalis).
AB  - Glucocorticoids modify metabolism and other physiological processes in order to
      mount an appropriate response to stress. This stress response is affected by a
      combination of seasonal changes, life-history events, and environmental factors.
      Determining seasonal variability and the potential connection between stress
      hormones and metabolism is fundamental in understanding seasonal physiological
      changes in animals. Here, we compared an indicator of stress (corticosterone)
      with an indicator of metabolic activity (uric acid-a non-enzymatic antioxidant
      and end product of protein metabolism) during capture and restraint in Northern
      Cardinals (Cardinalis cardinalis) during fall, winter, spring, and summer.
      Baseline corticosterone, the acute change in corticosterone (Delta10
      corticosterone), and integrated corticosterone during capture stress were
      significantly different among seasons. For all corticosterone measurements birds
      captured in summer consistently had the lowest values while spring birds were
      highest. The lower corticosterone stress response in summer may decrease the
      likelihood of abandonment and thus protect investment in eggs/chicks. Higher
      glucocorticoid secretion in spring may benefit birds competing for nesting sites.
      No differences in uric acid levels (baseline, 60 min, and acute change over 60
      min- Delta60-uric acid) were found among seasons. While plasma uric acid
      significantly decreased over an hour in all seasons examined, there were no
      significant correlations between baseline corticosterone and uric acid, time-60
      corticosterone and uric acid, and Delta10-corticosterone and Delta60-uric acid.
      We conclude that the relationship between corticosterone and metabolism, as
      measured by uric acid, is indirect, and seasonal variation occurs with
      corticosterone secretion but not with uric acid, as measured here.

PMID- 29356458
TI  - Corticosterone transdermal application in toads (Rhinella icterica): Effects on
      cellular and humoral immunity and steroid plasma levels.
AB  - Previous studies in a variety of vertebrates show stressed animals to exhibit
      acute increases in glucocorticoid levels, with consequences for immune
      modulation. Chronically elevated glucocorticoid levels are mostly associated with
      immunosuppression. However, there is still a paucity of knowledge regarding the
      amphibian physiological reaction to short- and long-term stress conditions,
      including glucocorticoid effects on the immune response. In order to better
      clarify the relationship between glucocorticoids and immune response, newly
      captured Brazilian toads (Rhinella icterica) (1 week in captivity) were subjected
      to a daily transdermal application (TA), of corticosterone or vehicle, for 30
      consecutive days. Measures were made on the first day (acute stressor) and last
      day (chronic stressor), at timepoints 1, 6, and 12 hr post TA. A number of
      variables were analyzed: corticosterone plasma levels (CORT);
      neutrophil/lymphocyte ratio (N:L); testosterone plasma levels (T); innate immune
      response, as indicated by bacterial killing ability (BKA); and whole blood
      phagocytosis. The corticosterone TA only simulated hormonal changes associated
      with the acute stress response, even after 30 consecutive days of the treatment,
      with the increased CORT in response after corticosterone TA being evident only 1
      hr postapplication and not thereafter. The general responses to corticosterone TA
      included increased CORT and N:L at first day of the treatment, and increased CORT
      and phagocytosis on the last day of the treatment. A decrease in T and BKA
      associated with the time in captivity was also evident, suggesting that captivity
      may be a chronic stressor for these toads.

PMID- 29356460
TI  - Repeatability and sources of variation of the bacteria-killing assay in the
      common snapping turtle.
AB  - Research on reptile ecoimmunology lags behind that on other vertebrates, despite
      the importance of such studies for conservation and evolution. Because the innate
      immune system is highly conserved across vertebrate lineages, assessments of its
      performance may be particularly useful in reptiles. The bacteria-killing assay
      requires a single, small blood sample and quantifies an individual's ability to
      kill microorganisms. The assay's construct validity and interpretability make it
      an attractive measure of innate immunity, but it requires proper optimization and
      sample storage. We optimized this assay for the common snapping turtle (Chelydra
      serpentina) to assess the repeatability of the assay and the effects of freezing
      and thawing on bactericidal capacity. We determined whether age (adult female and
      hatchlings) or incubation temperature influenced bactericidal capacity. We found
      that the assay was repeatable and that freezing plasma samples for 6 weeks at -80
      degrees C did not decrease bactericidal capacity nor did a single 30-min thaw and
      subsequent refreezing. However, we detected subtle interassay variation and
      results from one assay were 5-6% greater than those from the other two. Adult
      females had significantly greater bactericidal ability than hatchlings and we
      found no relationship between incubation temperature and bactericidal capacity.
      This assay is a useful tool in snapping turtles and may have applicability in
      other reptiles. However, species-specific optimization is required to ensure that
      variation among individuals exceeds interassay variation. Consideration should be
      given to optimization conditions that facilitate comparisons between or within
      groups, particularly groups that differ considerably in bactericidal capacity.

PMID- 29356459
TI  - Costs of immune responses are related to host body size and lifespan.
AB  - A central assumption in ecological immunology is that immune responses are
      costly, with costs manifesting directly (e.g., increases in metabolic rate and
      increased amino acid usage) or as tradeoffs with other life processes (e.g.,
      reduced growth and reproductive success). Across taxa, host longevity, timing of
      maturity, and reproductive effort affect the organization of immune systems. It
      is reasonable, therefore, to expect that these and related factors should also
      affect immune activation costs. Specifically, species that spread their breeding
      efforts over a long lifetime should experience lower immune costs than those that
      mature and breed quickly and die comparatively early. Likewise, body mass should
      affect immune costs, as body size affects the extent to which hosts are exposed
      to parasites as well as how hosts can combat infections (via its effects on
      metabolic rates and other factors). Here, we used phylogenetic meta-regression to
      reveal that, in general, animals incur costs of immune activation, but small
      species that are relatively long-lived incur the largest costs. These patterns
      probably arise because of the relative need for defense when infection risk is
      comparatively high and fitness can only be realized over a comparatively long
      period. However, given the diversity of species considered here and the overall
      modest effects of body mass and life history on immune costs, much more research
      is necessary before generalizations are appropriate.

PMID- 29356461
TI  - Association between ERalpha polymorphisms and systemic lupus erythematosus:
      susceptibility and in silico analysis.
AB  - BACKGROUND: Systemic lupus erythematous (SLE) is a multisystem and autoimmune
      disorder leading to damage of multi-organ systems. The current study aimed to
      assess the possible association between ERalpha gene polymorphisms and SLE in a
      southeast Iranian population. METHODS: The ERalpha PvuII and XbaI polymorphisms
      were genotyped by polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) method in 170 SLE patients and 186 healthy subjects.
      RESULTS: There was no association between ERalpha PvuII and XbaI polymorphisms
      and SLE susceptibility; however, the combination of the TC/AA and CC/GG genotypes
      of ESR alpha PvuII and XbaI polymorphisms were more frequent in SLE patients. The
      results indicated that TT haplotype of the ERalpha gene polymorphisms could
      increase the SLE risk almost 2.4-fold (odds ratio 2.4, 95% CI 1.3-4.3, P =
      0.005). The in silico analysis revealed that the ERalpha PvuII and XbaI single
      nucleotide polymorphisms occurred in acceptor splicing sites, and these mutations
      can lead to the increase of Human Splicing Finder score of the mutant alleles.
      CONCLUSIONS: The ESR alpha PvuII and XbaI polymorphisms have no association with
      SLE; however, the combination of the TC/AA and CC/GG genotypes were associated
      with SLE susceptibility.

PMID- 29356462
TI  - A randomized multicenter clinical trial of 99 Tc-methylene diphosphonate in
      treatment of rheumatoid arthritis.
AB  - AIM: To investigate the efficacy and safety of technetium-99 conjugated with
      methylene diphosphonate (99 Tc-MDP, Yunke Pharmaceutical industry) in the
      treatment of rheumatoid arthritis (RA). METHODS: A total of 120 patients with
      active RA were randomly divided into three groups: Group A (receiving oral
      meloxicam tablets); Group B (receiving intravenous drip of 99 TC-MDP); Group C
      (receiving combination treatment of intravenous drip of 99 Tc-MDP and oral
      meloxicam tablets). The main clinical and laboratory parameters were evaluated at
      baseline and after 14 days of therapy. RESULTS: After 14 days of treatment,
      American College of Rheumatology 20 response was 15.62%, 34.04% and 48.78% in the
      three groups, respectively. The incidence of adverse events in three groups were
      3.13%, 8.51% and 9.76% respectly, and has no significant difference. In addition,
      biochemical markers of bone metabolism including bone alkaline phosphatase (BAP),
      tartrate resistant acid phosphatase (TRAP) and dickkopf-1 (DKK-1), all improved
      in the three groups, although more significant in Group B than Group A, and more
      significant in the combination group than monotherapy groups. CONCLUSION: 99 Tc
      MDP has good efficacy and safety in the treatment of active RA patients; the
      benefit was more remarkable when 99 Tc-MDP was combined with NSAIDs. 99 Tc-MDP
      may also have potential to improve bone metabolism.

PMID- 29356464
TI  - Thermal performance and acclimatization of a component of snake (Agkistrodon
      piscivorus) innate immunity.
AB  - Complement-an immune protein cascade involved in pathogen lysis-was discovered as
      a temperature-labile component of vertebrate plasma, yet since that time the
      thermal performance of complement has not received much attention from a
      comparative or ecological perspective. We investigated two thermal hypotheses
      involving the complement system of the cottonmouth snake (Agkistrodon
      piscivorus). We tested whether complement performance would conform to optimal
      thermal reaction norms commonly observed in ectotherm ecophysiological studies,
      predicting that complement efficiency would be maximal at or near the
      cottonmouth's field body temperatures. We also tested thermal acclimatization of
      complement performance, by comparing temperature/performance curves from samples
      collected in three different seasons. Complement efficiency exhibited the same
      significant positive correlation with temperature in all three seasons. This
      seasonally invariable temperature-performance relationship may allow easy
      acquisition of behavioral fever, as well as trade-offs between immune performance
      and energy balance, ultimately endowing snakes with immunological flexibility not
      available to endotherms.

PMID- 29356463
TI  - Spatial barriers impact upon appropriate delivery of radiotherapy in breast
      cancer patients.
AB  - Radiotherapy (RT) is the standard treatment for breast cancer patients after
      conserving surgery or mastectomy when patients are at high risk of relapse. Major
      obstacles to appropriate RT delivery are journey times. Since studies on access
      to RT were carried out mostly in large countries, this study investigated factors
      in an Italian region and the influence of RT delivery on survival. A total of
      4735 female candidates for RT were included in the study. A geographic
      information system calculated journey times from patients' homes and surgery
      hospitals to RT centers. Logistic regression analyzed the influence of journey
      times, socioeconomic status, and other factors on RT delivery. Survival
      probabilities and excess mortality were assessed in 4364 propensity score-matched
      patients. Journey times of 40 min or less from residence and from surgery
      hospital to RT center played a major role in access to RT. A large survival
      difference emerged between treated and untreated breast cancer patients. The
      excess mortality for untreated patients compared with propensity score-matched
      women receiving RT was 3.1 (95% CI: 2.2-4.3). Expansion of RT facilities during
      the 11-year study period improved RT delivery and outcomes by increasing
      availability but mainly by shortening journey times.

PMID- 29356493
TI  - Cross-Linking-Mass Spectrometry Studies of Cholesterol Interactions with Human
      alpha1 Glycine Receptor.
AB  - The glycine receptor (GlyR) belongs to a superfamily of pentameric ligand-gated
      ion channels (pLGICs) that mediate fast neurotransmission. GlyR typically
      modulates inhibitory transmission by antagonizing membrane depolarization through
      anion influx. Allosteric interactions between the receptor and its lipid
      surroundings affect receptor function, and cholesterol is essential for pLGIC
      activity. Cholesterol at compositions below ~33 mol percent has been shown to
      have negligible chemical activity, suggesting that specific interactions between
      membrane proteins and cholesterol become significant only at concentrations above
      this stoichiometric threshold. Human alpha1 GlyR was purified from baculovirus
      infected insect cells and reconstituted in unilamellar vesicles at
      cholesterol/lipid ratios above and below the cholesterol activity threshold with
      equivalent aliquots of azi-cholesterol, a photoactivatable nonspecific cross
      linker. After photoactivation, cross-linked cholesterol-GlyR was trypsinized and
      mass fingerprinted. Mass shifted peptides containing cholesterol were identified
      by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF
      MS), and sites of direct covalent attachment to peptides were refined by targeted
      MS/MS. Differential patterns of dozens of cholesterol-GlyR cross-links were
      identified in these comparative studies, with sites of cross-linking found
      primarily in the fourth transmembrane helix and extramembranous connecting loops
      and mapping the lipid-accessible surface of the receptor. Unique cross-linking
      observed in both reduced and elevated cholesterol composition suggests different
      apo-state structural conformations of GlyR as a function of cholesterol
      concentration and, in the latter studies, identified potential specific binding
      sites for cholesterol in the receptor.

PMID- 29356494
TI  - Controlling the Release from Enzyme-Responsive Microcapsules with a Smart Natural
      Shell.
AB  - We design a natural and simple core-shell-structured microcapsule, which releases
      its cargo only when exposed to lipase. The cargo is entrapped inside a gel
      matrix, which is surrounded by a double-layer shell containing an inner solid
      lipid layer and an outer polymer layer. This outer polymer layer can be designed
      according to the intended biological system and is responsible for protecting the
      microcapsule architecture and transporting the cargo to the desired site of
      action. The lipid layer contains natural ester bonds, which are digested by
      lipase, controlling the release of cargo from the microcapsule core. To
      demonstrate the feasibility of this approach, our model system includes a
      colorant bixin entrapped inside a kappa-carrageenan gel matrix. This core is
      surrounded by an inner beeswax-palmitic acid layer and an outer casein-poloxamer
      338 layer. These fabricated microcapsules are then applied into Cheddar cheese,
      where they selectively color the cheese matrix.

PMID- 29356495
TI  - Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of
      Heterobifunctional Phthalimide Degraders.
AB  - Protein degradation is an emerging therapeutic strategy with a unique molecular
      pharmacology that enables the disruption of all functions associated with a
      target. This is particularly relevant for proteins depending on molecular
      scaffolding, such as transcription factors or receptor tyrosine kinases (RTKs).
      To address tractability of multiple RTKs for chemical degradation by the E3
      ligase CUL4-RBX1-DDB1-CRBN (CRL4CRBN), we synthesized a series of phthalimide
      degraders based on the promiscuous kinase inhibitors sunitinib and PHA665752.
      While both series failed to induce degradation of their consensus targets,
      individual molecules displayed pronounced efficacy in leukemia cell lines.
      Orthogonal target identification supported by molecular docking led us to
      identify the translation termination factor G1 to S phase transition 1 (GSPT1) as
      a converging off-target, resulting from inadvertent E3 ligase modulation. This
      research highlights the importance of monitoring degradation events that are
      independent of the respective targeting ligand as a unique feature of small
      molecule degraders.

PMID- 29356496
TI  - Durably Antibacterial and Bacterially Antiadhesive Cotton Fabrics Coated by
      Cationic Fluorinated Polymers.
AB  - Considerable attention has been devoted to producing antibacterial fabrics due to
      their very wide applications in medicine, hygiene, hospital, etc. However, the
      poor antibacterial durability and bad bacterial antiadhesion capacity of most
      existing antibacterial fabrics limit their applications. In this work, a series
      of antibacterial and polymeric quaternary ammonium monomers with different alkyl
      chain length were successfully synthesized to copolymerize with fluorine
      containing and other acrylic monomers to generate cationic fluorinated polymer
      emulsions and durably antibacterial and bacterially antiadhesive cotton fabrics.
      The relation between antibacterial constituent and its antibacterial activity was
      investigated. The study indicated that the alkyl chain length and contents of the
      antibacterial monomers, as well as the add-on percentage of polymer greatly
      influenced the antibacterial activities of the fabrics. In addition, it was found
      that incorporation of fluorine component into the polymer greatly enhanced the
      antibacterial activity and bacterial antiadhesion of the treated fabrics due to
      the low surface energy induced hydrophobicity. Finally, antibacterial and
      antiadhesive models of action of the obtained fabrics were illustrated.

PMID- 29356497
TI  - Effect of Systematic Hydrogenation on the Phase Behavior and Nanostructural
      Dimensions of Block Copolymers.
AB  - Unsaturated polydienes are frequently hydrogenated to yield polyolefins that are
      more chemically stable. Here, the effects of partial hydrogenation on the phase
      behavior and nanostructure of polyisoprene-containing block copolymers are
      investigated. To ensure access to the order-disorder transition temperature
      (TODT) over a wide temperature range, we examine copolymers with at least one
      random block. Dynamic rheological and scattering measurements indicate that TODT
      increases linearly with increasing hydrogenation. Small-angle scattering reveals
      that the temperature-dependence of the Flory-Huggins parameter changes and the
      microdomain period increases, while the interfacial thickness decreases. The
      influence of hydrogenation becomes less pronounced in more constrained multiblock
      copolymers.

PMID- 29356498
TI  - Lysosome Enlargement Enhanced Photochemotherapy Using a Multifunctional Nanogel.
AB  - Large lysosomes are susceptible toward rupture because of an increased membrane
      tension. Here we report a strategy to first enlarge and weaken the lysosome and
      then destroy it to boost the efficiency of photochemotherapy using a hyaluronan
      nanogel, carrying chloroquine as a lysosomal expander, rhodamine B as a
      photosensitive lysosomal destroyer, and cisplatin as a chemotherapeutic. This all
      in-one nanogel provides a facile approach and new insight into improve the
      photochemotherapy, by making use of lysosome's size, as a risk factor in
      lysosomal destabilization.

PMID- 29356499
TI  - Mechanistic Understanding Leads to Increased Ionization Efficiency and
      Selectivity in Dielectric Barrier Discharge Ionization Mass Spectrometry: A Case
      Study with Perfluorinated Compounds.
AB  - Perfluorinated compounds have unique properties and many practical applications,
      but are difficult to ionize efficiently with soft ionization methods. An active
      capillary plasma ionization source based on dielectric barrier discharge
      ionization (DBDI) coupled with mass spectrometry was used to study the ionization
      pathway of perfluorinated compounds (PFCs), with the aim of both increasing the
      ionization efficiency and influencing the selectivity for generating product ions
      in negative ion mode. Cyclic and linear perfluorinated alkanes were found to
      mainly form [M - F]- and [M - F + O]- ions, respectively; the [M]-* ion was only
      obtained at low discharge voltage. Additionally, fluorine attachment [M + F]- was
      observed mostly for perfluorinated alkenes. An isotope labeling experiment with
      18O2 showed that the primary source of oxygen in the substitution reaction is
      molecular oxygen, reacting with the analyte in the form of O-* ions. The
      abundance of [M - F + O]- ions can thus be enhanced by increasing the plasma
      voltage to produce a higher O-* ion density. The loss of the fluorine (without
      substitution by oxygen) was mainly observed at high frequency, a fact which can
      be exploited for tuning the ionization toward specific product ions. Overall, the
      mechanistic understanding of the ionization of PFCs allowed to increase the
      selectivity of the product ions, resulting in increased ionization efficiency.

PMID- 29356500
TI  - Investigation of Dual-Ion Beam Sputter-Instigated Plasmon Generation in TCOs: A
      Case Study of GZO.
AB  - The use of the high free-electron concentration in heavily doped semiconductor
      enables the realization of plasmons. We report a novel approach to generate
      plasmons in Ga:ZnO (GZO) thin films in the wide spectral range of ~1.87-10.04 eV.
      In the grown GZO thin films, dual-ion beam sputtering (DIBS) instigated plasmon
      is observed because of the formation of different metallic nanoclusters are
      reported. Moreover, formation of the nanoclusters and generation of plasmons are
      verified by field emission scanning electron microscope, electron energy loss
      spectra obtained by ultraviolet photoelectron spectroscopy, and spectroscopic
      ellipsometry analysis. Moreover, the calculation of valence bulk, valence
      surface, and particle plasmon resonance energies are performed, and indexing of
      each plasmon peaks with corresponding plasmon energy peak of the different
      nanoclusters is carried out. Further, the use of DIBS-instigated plasmon-enhanced
      GZO can be a novel mean to improve the performance of photovoltaic,
      photodetector, and sensing devices.

PMID- 29356501
TI  - Cyanostar: C-H Hydrogen Bonding Neutral Carrier Scaffold for Anion-Selective
      Sensors.
AB  - Cyanostar, a pentagonal macrocyclic compound with an electropositive cavity,
      binds anions with CH-based hydrogen bonding. The large size of the cyanostar's
      cavity along with its planarity favor formation of 2:1 sandwich complexes with
      larger anions, like perchlorate, ClO4-, relative to the smaller chloride. We also
      show that cyanostar is selective for ClO4- over the bulky salicylate anions by
      using NMR titration studies to measure affinity. The performance of this novel
      macrocycle as an anion ionophore in membrane ion sensors was evaluated. The
      cyanostar-based electrodes demonstrated a Nernstian response toward perchlorate
      with selectivity patterns distinctly different from the normal Hofmeister series.
      Different membrane compositions were explored to identify the optimum
      concentrations of the ionophore, plasticizer, and lipophilic additive that give
      rise to the best perchlorate selectivity. Changing the concentration of the
      lipophilic additive tridodecylmethylammonium chloride was found to impact the
      selectivity pattern and the analytical dynamic range of the electrodes. The high
      selectivity of the cyanostar sensors and their detection limit could enable the
      determination of ClO4- in contaminated environmental samples. This novel class of
      macrocycle provides a suitable scaffold for designing various anion-selective
      ionophores by altering the size of the central cavity and its functionalization.

PMID- 29356502
TI  - Crystallographic Structure Analysis of a Ti-Ta Thin Film Materials Library
      Fabricated by Combinatorial Magnetron Sputtering.
AB  - Ti-Ta thin films exhibit properties that are of interest for applications as
      microactuators and as biomedical implants. A Ti-Ta thin film materials library
      was deposited at T = 25  degrees C by magnetron sputtering employing the
      combinatorial approach, which led to a compositional range of Ti87Ta13 to
      Ti14Ta86. Subsequent high-throughput characterization methods permitted a quick
      and comprehensive study of the crystallographic, microstructural, and
      morphological properties, which strongly depend on the chemical composition. SEM
      investigation revealed a columnar morphology having pyramidal, sharp tips with
      coarser columns in the Ti-rich and finer columns in the Ta-rich region. By
      grazing incidence X-ray diffraction four phases were identified, from Ta-lean to
      Ta-rich: omega phase, alpha" martensite, beta phase, and a tetragonal Ta-rich
      phase (Ta(tetr)). The crystal structure and microstructure were analyzed by
      Rietveld refinement and clear trends could be determined as a function of Ta
      content. The lattice correspondences between beta as the parent phase and alpha"
      and omega as derivative phases were expressed in matrix form. The beta ? alpha"
      phase transition shows a discontinuity at the composition where the martensitic
      transformation temperatures fall below room temperature (between 34 and 38 at. %
      Ta) rendering it first order and confirming its martensitic nature. A short study
      of the alpha" martensite employing the Landau theory is included for a
      mathematical quantification of the spontaneous lattice strain at room temperature
      (epsilonmax = 22.4(6) % for pure Ti). Martensitic properties of Ti-Ta are
      beneficial for the development of high-temperature actuators with actuation
      response at transformation temperatures higher than 100  degrees C.

PMID- 29356503
TI  - Frequency-Modulated Continuous Flow Analysis Electrospray Ionization Mass
      Spectrometry (FM-CFA-ESI-MS) for Sample Multiplexing.
AB  - A method for multiplexed sample analysis by mass spectrometry without the need
      for chemical tagging is presented. In this new method, each sample is pulsed at
      unique frequencies, mixed, and delivered to the mass spectrometer while
      maintaining a constant total flow rate. Reconstructed ion currents are then a
      time-dependent signal consisting of the sum of the ion currents from the various
      samples. Spectral deconvolution of each reconstructed ion current reveals the
      identity of each sample, encoded by its unique frequency, and its concentration
      encoded by the peak height in the frequency domain. This technique is different
      from other approaches that have been described, which have used modulation
      techniques to increase the signal-to-noise ratio of a single sample. As proof of
      concept of this new method, two samples containing up to 9 analytes were
      multiplexed. The linear dynamic range of the calibration curve was increased with
      extended acquisition times of the experiment and longer oscillation periods of
      the samples. Because of the combination of the samples, salt had little effect on
      the ability of this method to achieve relative quantitation. Continued
      development of this method is expected to allow for increased numbers of samples
      that can be multiplexed.

PMID- 29356504
TI  - Morphology of OLED Film Stacks Containing Solution-Processed Phosphorescent
      Dendrimers.
AB  - Organic light-emitting devices containing solution-processed emissive dendrimers
      can be highly efficient. The most efficient devices contain a blend of the light
      emitting dendrimer in a host and one or more charge-transporting layers. Using
      neutron reflectometry measurements with in situ photoluminescence, we have
      investigated the structure of the as-formed film as well as the changes in film
      structure and dendrimer emission under thermal stress. It was found that the as
      formed film stacks comprising poly(3,4-ethylenedioxythiophene):polystyrene
      sulfonate/host:dendrimer/1,3,5-tris(N-phenylbenzimidazol-2-yl)benzene (where the
      host was deuterated 4,4'-N,N'-di(carbazolyl)biphenyl or tris(4-carbazol-9
      ylphenyl)amine, the host:dendrimer layer was solution-processed, and the 1,3,5
      tris(N-phenylbenzimidazol-2-yl)benzene evaporated) had well-defined interfaces,
      indicating good wetting of each of the layers by the subsequently deposited
      layer. Upon thermal annealing, there was no change in the poly(3,4
      ethylenedioxythiophene):polystyrene sulfonate/host:dendrimer interface, but once
      the temperature reached above the Tg of the host:dendrimer layer, it became a
      supercooled liquid into which 1,3,5-tris(N-phenylbenzimidazol-2-yl)benzene
      dissolved. When the film stacks were held at a temperature just above the onset
      of the diffusion process, they underwent an initial relatively fast diffusion
      process before reaching a quasi-stable state at that temperature.

PMID- 29356505
TI  - CNT-Decorated Na3V2(PO4)3 Microspheres as a High-Rate and Cycle-Stable Cathode
      Material for Sodium Ion Batteries.
AB  - A novel cathode material, carbon nanotube (CNT)-decorated Na3V2(PO4)3 (NVP)
      microspheres, was designed and synthesized via spray-drying and carbothermal
      reduction methods. The microspheres were covered and embedded by CNTs, the
      surfaces of which were also covered by amorphous carbon layers. Thus, a carbon
      network composed of CNTs and amorphous carbon layers formed in the materials. The
      polarization of a 10 wt % CNT-decorated NVP (NVP/C10) electrode was much less
      compared with that of the electrode with pristine NVP without CNTs. The capacity
      of the NVP/C10 electrode only decreased from 103.2 to 76.2 mAh g-1 when the
      current rates increased from 0.2 to 60 C. Even when cycled at a rate of 20 C, the
      initial discharge capacity of the NVP/C10 electrode was as high as 91.2 mAh g-1,
      and the discharge capacity was 76.9 mAh g-1 after 150 cycles. The charge-transfer
      resistance and ohmic resistance became smaller because of CNT decorating.
      Meanwhile, the addition of CNTs can tune the size of the NVP particles and
      increase the contact area between NVP and the electrolyte. Consequently, the
      resulted NVP had a larger sodium ion diffusion coefficient than that of the
      pristine NVP.

PMID- 29356506
TI  - Comparing Strategies in the Design of Responsive Contrast Agents for Magnetic
      Resonance Imaging: A Case Study with Copper and Zinc.
AB  - Magnetic resonance imaging (MRI) has emerged over the years as one of the
      preferred modalities for medical diagnostic and biomedical research. It has the
      advantage over other imaging modalities such as positron emission tomography and
      X-ray of affording high resolution three-dimensional images of the body without
      using harmful radiation. The use of contrast agents has further expanded this
      technique by increasing the contrast between regions where they accumulate and
      background tissues. As MRI most often measures the relaxation rate of water
      throughout the body, contrast agents function by modulating the intensity of the
      water signal either via improved relaxation or via saturation transfer to
      selected exchangeable proton. Among the growing class of MRI contrast agents, a
      subset of them called "smart" contrast agents function as responsive probes.
      Their ability to increase or decrease their signal intensity is modulated by the
      presence of an analyte. These probes offer the unique ability to image the
      distribution of an analyte in vivo, thereby opening new possibilities for
      diagnostics and for elucidating the role of specific analytes in various
      pathologies or biological processes. A number of different strategies can be
      exploited to design responsive MRI contrast agents. The majority of contrast
      agents are based on GdIII complexes. These complexes can be rendered responsive
      in either of two ways: either by modulating the number of inner-sphere water
      molecules, q, or via modulating the rotational correlation time, tauR, of the
      contrast agent upon substrate binding. The longitudinal relaxivity increases with
      the number of inner-sphere water molecules. GdIII complexes can be rendered
      responsive if they contain a recognition moiety that can bind to both the open
      coordination site of GdIII and to the analyte. When the recognition moiety leaves
      the lanthanide ion to bind to the analyte, q increases and therefore so does the
      relaxivity. The dependence of relaxivity on rotational correlation time is more
      complex and more pronounced at lower magnetic fields. In general, slower tumbling
      macromolecules have longer rotational correlation times and higher relaxivities.
      Analyte-triggered formation of macromolecules thus also increases relaxivity.
      Such macromolecules can either be analyte-templated supramolecular assemblies, or
      analyte-enhanced protein-contrast agent complexes. Chemical Exchange Saturation
      Transfer (CEST) agents are a newer class of contrast agents that offer the
      possibility of multifrequency and thus ratiometric imaging, which in turn enables
      quantitative mapping of the concentration of an analyte in vivo under conditions
      where the concentration of the contrast agent is not known. Such agents can be
      rendered responsive if the analyte changes the number of exchangeable proton(s),
      its exchange rate, or its chemical shift. All of these approaches have been
      successfully employed for detecting and imaging both copper and zinc, including
      in vivo. Magnetic Iron Oxide Nanoparticles (MIONs) are powerful MRI transverse
      relaxation agents. They can also be rendered responsive to an analyte if the
      latter can control the aggregation of the nanoparticles. For metal ions, this can
      be achieved via chemical functionalities that only react to form conjugates in
      the presence of the metal ion analyte.

PMID- 29356507
TI  - Mechanistic Investigation into the Selective Anticancer Cytotoxicity and Immune
      System Response of Surface-Functionalized, Dichloroacetate-Loaded, UiO-66
      Nanoparticles.
AB  - The high drug-loading and excellent biocompatibilities of metal-organic
      frameworks (MOFs) have led to their application as drug-delivery systems (DDSs).
      Nanoparticle surface chemistry dominates both biostability and dispersion of DDSs
      while governing their interactions with biological systems, cellular and/or
      tissue targeting, and cellular internalization, leading to a requirement for
      versatile and reproducible surface functionalization protocols. Herein, we
      explore not only the effect of introducing different surface functionalities to
      the biocompatible Zr-MOF UiO-66 but also the efficacy of three surface
      modification protocols: (i) direct attachment of biomolecules [folic acid (FA)
      and biotin (Biot)] introduced as modulators for UiO-66 synthesis, (ii) our
      previously reported "click-modulation" approach to covalently attach polymers
      [poly(ethylene glycol) (PEG), poly-l-lactide, and poly-N-isopropylacrylamide] to
      the surface of UiO-66 through click chemistry, and (iii) surface ligand exchange
      to postsynthetically coordinate FA, Biot, and heparin to UiO-66. The innovative
      use of a small molecule with metabolic anticancer activity, dichloroacetate
      (DCA), as a modulator during synthesis is described, and it is found to be
      compatible with all three protocols, yielding surface-coated, DCA-loaded (10-20
      w/w %) nano-MOFs (70-170 nm). External surface modification generally enhances
      the stability and colloidal dispersion of UiO-66. Cellular internalization routes
      and efficiencies of UiO-66 by HeLa cervical cancer cells can be tuned by surface
      chemistry, and anticancer cytotoxicity of DCA-loaded MOFs correlates with the
      endocytosis efficiency and mechanisms. The MOFs with the most promising coatings
      (FA, PEG, poly-l-lactide, and poly-N-isopropylacrylamide) were extensively tested
      for selectivity of anticancer cytotoxicity against MCF-7 breast cancer cells and
      HEK293 healthy kidney cells as well as for cell proliferation and reactive oxygen
      species production against J774 macrophages and peripheral blood lymphocytes
      isolated from the blood of human donors. DCA-loaded, FA-modified UiO-66
      selectively kills cancer cells without harming healthy ones or provoking immune
      system response in vitro, suggesting a significant targeting effect and great
      potential in anticancer drug delivery. The results provide mechanistic insight
      into the design and functionalization of MOFs for drug delivery and underline the
      availability of various in vitro techniques to potentially minimize early-stage
      in vivo animal studies following the three Rs: reduction, refinement, and
      replacement.

PMID- 29356508
TI  - High-Efficiency Cycloruthenated Sensitizers for Dye-Sensitized Solar Cells.
AB  - Four thiocyanate-free ruthenium sensitizers (DUY24-DUY27) containing 2
      thienylpyridine moiety as cyclometalating core were synthesized for dye
      sensitized solar cell (DSC) application. To the best of our knowledge, DUY24
      DUY27 are four best-efficiency sensitizers having 42%-65% higher efficiencies
      compared to those of the published sensitizers comprising the same type of the
      cyclometalating ancillary ligands. The significant characteristic of DUY24-DUY27
      is their beta-lowest unoccupied spin orbital (beta-LUSO) distributes remarkably
      on the cyclometalating ligands, especially on the soft sulfur atom, which
      strengthens the interaction between the oxidized dye and iodide ion for efficient
      dye regeneration. The photovoltaic performance of DUY24-DUY27-based DSCs supports
      that the dye regeneration (therefore the short-circuit photocurrent density (JSC)
      of the cell) can be improved by not only lowering the highest occupied molecular
      orbital energy level of the dye molecule but also distributing the beta-LUSO
      properly on the soft atoms. The study provides an important new guide for
      designing high-efficiency ruthenium-based dyes for DSC application.

PMID- 29356509
TI  - Conjugation Chemistry-Dependent T-Cell Activation with Spherical Nucleic Acids.
AB  - Spherical nucleic acids (SNAs) can be potent sequence-specific stimulators of
      antigen presenting cells (APCs). When loaded with peptide antigens, they can be
      used to activate the immune system to train T-cells to specifically kill cancer
      cells. Herein, the role of peptide chemical conjugation to the DNA, which is used
      to load SNAs with antigens via hybridization, is explored in the context of APC
      activation. Importantly, though the antigen chemistry does not impede TLR-9
      regulated APC activation, it significantly augments the downstream T-cell
      response in terms of both activation and proliferation. A comparison of three
      linker types, (1) noncleavable, (2) cleavable but nontraceless, and (3)
      traceless, reveals up to an 8-fold improvement in T-cell proliferation when the
      traceless linker is used. This work underscores the critical importance of the
      choice of conjugation chemistry in vaccine development.

PMID- 29356510
TI  - Amendment of Agricultural Soil with Metal Nanoparticles: Effects on Soil Enzyme
      Activity and Microbial Community Composition.
AB  - Several types of engineered nanoparticles (ENPs) are being considered for direct
      application to soils to reduce the application and degradation of pesticides,
      provide micronutrients, control pathogens, and increase crop yields. This study
      examined the effects of different metal ENPs and their dissolved ions on the
      microbial community composition and enzyme activity of agricultural soil amended
      with biosolids. The activity of five extracellular nutrient-cycling enzymes was
      measured in biosolid-amended soils treated with different concentrations (1, 10,
      or 100 mg ENP/kg soil) of silver (nAg), zinc oxide (nZnO), copper oxide (nCuO),
      or titanium dioxide (nTiO2) nanoparticles and their ions over a 30-day period. At
      30 days, nZnO and nCuO either had no significant effect on soil enzyme activity
      or enhanced enzyme activity. In contrast, Ag inhibited selected enzymes when
      dosed in particulate or dissolved form (at 100 mg/kg). nTiO2 either had no
      significant effect or slightly decreased enzyme activity. Illumina MiSeq
      sequencing of microbial communities indicated a shift in soil microbial community
      composition upon exposure to high doses of metal ions or nAg and negligible shift
      in the presence of nTiO2. Some taxa responded differently to nAg and Ag+. This
      work shows how metal ENPs can impact soil enzyme activity and microbial community
      composition upon introduction into soils amended with biosolids, depending on
      their type, concentration, and dissolution behavior, hence providing much needed
      information for the sustainable application of nanotechnology in agriculture.

PMID- 29356511
TI  - Synthesis and Characterization of Heterobimetallic Iridium-Aluminum and Rhodium
      Aluminum Complexes.
AB  - We demonstrate the synthesis and characterization of a new class of late
      transition-metal-aluminum heterobimetallic complexes via a novel synthetic
      pathway. Complexes of this type are exceedingly rare. Joint experimental and
      theoretical data sheds light on the electronic effect of ligands containing
      aluminum moieties on late-transition-metal complexes.

PMID- 29356512
TI  - Characterization of Clinically Relevant Fungi via SERS Fingerprinting Assisted by
      Novel Chemometric Models.
AB  - Nonculture-based tests are gaining popularity and upsurge in the diagnosis of
      invasive fungal infections (IFI) fostered by their main asset, the reduced
      analysis time, which enables a more rapid diagnosis. In this project, three
      different clinical isolates of relevant filamentous fungal species were
      discriminated by using a rapid (less than 5 min) and sensitive surface-enhanced
      Raman scattering (SERS)-based detection method, assisted by chemometrics. The
      holistic evaluation of the SERS spectra was performed by employing appropriate
      chemometric tools-classical and fuzzy principal component analysis (FPCA) in
      combination with linear discriminant analysis (LDA) applied to the first relevant
      principal components. The efficiency of the proposed robust algorithm is
      illustrated on the data set including three fungal isolates (Aspergillus
      fumigatus sensu stricto, cryptic A. fumigatus complex species, and Rhizomucor
      pusillus) that were isolated from patient materials. The accurate and reliable
      discrimination between species of common fungal pathogen strains suggest that the
      developed method has the potential as an alternative, spectroscopic-based routine
      analysis tool in IFI diagnosis.

PMID- 29356513
TI  - Role of Synthesis Method on Luminescence Properties of Europium(II, III) Ions in
      beta-Ca2SiO4: Probing Local Site and Structure.
AB  - The europium ion probes the symmetry disorder in the crystal structure, although
      the distortion due to charge compensation in the case of aliovalent dopant
      remains interesting, especially preparation involves low and high temperatures.
      This work studies the preparation of the beta-Ca2SiO4 (from here on C2S) particle
      from Pechini (C2SP) and hydrothermal (C2SH) methods, and its luminescence
      variance upon doping with Eu2+ and Eu3+ ions. The blue shift of the charge
      transfer band (CTB) in the excitation spectra indicates a larger Eu3+-O2-
      distance in Eu3+ doped C2SH. The changes in vibrational frequencies due to
      stretching and bending vibrations in the FTIR and the Raman spectra and binding
      energy shift in the XPS analysis confirmed the distorted SiO44- tetrahedra in
      C2SH. The high hydrothermal temperature and pressure produce distortion, which
      leads to symmetry lowering although doping of aliovalent ion may slightly change
      the position of the Ca atoms. The increasing asymmetry ratio value from C2SP to
      C2SH clearly indicates that the europium ion stabilized in a more distorted
      geometry. It is also supported by Judd-Ofelt analysis. The concentration
      quenching and site-occupancy of Eu3+ ions in two nonequivalent sites of C2S were
      discussed. The charge state and concentration of europium ions in C2SP and C2SH
      were determined using X-ray photoelectron spectroscopy measurements. The C2S
      particles were studied by X-ray powder diffraction, FTIR, Raman, BET surface
      area, TGA/DTA, electron microscopy, XPS, and luminescence spectroscopy. The
      impact of citrate ion on the morphology and particle size of C2SH has been
      hypothesized on the basis of the microscopy images. This study provides insights
      that are needed for further understanding the structure of C2S and thereby
      improves the applications in optical and biomedical areas and cement hydration.

PMID- 29356514
TI  - One-Step Solution Combustion Synthesis of Cobalt Nanopowder in Air Atmosphere:
      The Fuel Effect.
AB  - In this paper, we report a new modified solution combustion synthesis technique
      for one-step production of metallic Co nanoparticles. The main unique feature of
      our approach is the use of microwave-assisted foam preparation. Also, the effect
      of different types of fuels (urea, citric acid, glycine, and
      hexamethylenetetramine) on the combustion process and characteristics of
      resultant solid products were investigated. It was shown that the combination of
      microwave-assisted foam and hexamethylenetetramine as a fuel allows us to produce
      metallic Co nanoparticles with the broad size distribution (~5-40 nm), high
      coercivity (370 Oe), and high value of saturation magnetization (137 emu/g) by
      the one-step solution combustion synthesis under normal air atmosphere without
      any post reduction.

PMID- 29356515
TI  - Dysregulation of Intestinal Health by Environmental Pollutants: Involvement of
      the Estrogen Receptor and Aryl Hydrocarbon Receptor.
AB  - To determine how environmental pollutants induce dysbiosis of the gut microbiota,
      we exposed adult zebrafish to model pollutants with varied modes of action
      (atrazine, estradiol, polychlorinated biphenyl [PCB]126, and PCB153) for 7 days.
      Subsequently, metagenomic sequencing of the intestines was performed to compare
      the gut microbiomes among the groups. We observed clear compound- and sex
      specific responses to xenobiotic stress. Principal component analysis revealed
      involvement of the aryl hydrocarbon receptor (AhR) and, to a lesser extent, the
      estrogen receptor (ER) in the dysregulation of the intestinal microbiota. The
      model pollutants differentially impaired intestinal and hepatic physiological
      activities, as indicated by assessments of gut motility, epithelial permeability,
      inflammation, and oxidative stress. Correlation analysis showed that abnormal
      Aeromonas reproduction, especially in the PCB126 groups, was significantly
      positively associated with oxidative damage. Aeromonas closely interacted with
      Mannheimia and Blastococcus to regulate intestinal permeability. In summary, we
      demonstrated that ER and AhR signaling regulated the dynamics of the gut
      microbiota. Our findings provide new mechanistic insight into the complex
      interactions between the host metabolism and gut microbiota, which may contribute
      to the grouped assessment of environmental pollutants in future.

PMID- 29356516
TI  - Stereochemical Sequence Dictates Unimolecular Diblock Copolymer Assembly.
AB  - Deciphering the significance of length, sequence, and stereochemistry in block
      copolymer self-assembly remains an ongoing challenge. A dearth of methods to
      access uniform block co-oligomers/polymers with precise stereochemical sequences
      has precluded such studies. Here, we develop iterative exponential growth methods
      for the synthesis of a small library of unimolecular stereoisomeric diblock 32
      mers. X-ray scattering reveals that stereochemistry modulates the phase behavior
      of these polymers, which we rationalize based on simulations carried out on a
      theoretical model system. This work demonstrates that stereochemical sequence can
      play a crucial role in unimolecular polymer self-assembly.

PMID- 29356517
TI  - Combined Approach for the Structural Characterization of Alkali Fluoroscandates:
      Solid-State NMR, Powder X-ray Diffraction, and Density Functional Theory
      Calculations.
AB  - The structures of several fluoroscandate compounds are presented here using a
      characterization approach combining powder X-ray diffraction and solid-state NMR.
      The structure of K5Sc3F14 was fully determined from Rietveld refinement performed
      on powder X-ray diffraction data. Moreover, the local structures of NaScF4,
      Li3ScF6, KSc2F7, and Na3ScF6 compounds were studied in detail from solid-state
      19F and 45Sc NMR experiments. The 45Sc chemical shift ranges for six- and seven
      coordinated scandium environments were defined. The 19F chemical shift ranges for
      bridging and terminal fluorine atoms were also determined. First-principles
      calculations of the 19F and 45Sc NMR parameters were carried out using plane-wave
      basis sets and periodic boundary conditions (CASTEP), and the results were
      compared with the experimental data. A good agreement between the calculated
      shielding constants and experimental chemical shifts was obtained. This
      demonstrates the good potential of computational methods in spectroscopic
      assignments of solid-state 45Sc NMR spectroscopy.

PMID- 29356518
TI  - Palladium(II)-Stabilized Pyridine-2-Diazotates: Synthesis, Structural
      Characterization, and Cytotoxicity Studies.
AB  - Well-defined diazotates are scarce. Here we report the synthesis of unprecedented
      homoleptic palladium(II) diazotate complexes. The palladium(II)-mediated
      nitrosylation of 2-aminopyridines with NaNO2 results in the formation of metal
      stabilized diazotates, which were found to be cytotoxic to human ovarian cancer
      cells.

PMID- 29356519
TI  - Improved Quantitative SERS Enabled by Surface Plasmon Enhanced Elastic Light
      Scattering.
AB  - The application of surface-enhanced Raman spectroscopy (SERS) for everyday
      quantitative analysis is hindered by the point-to-point variability of SERS
      substrates that arises due to the heterogeneous distribution of localized
      electromagnetic fields across a suite of plasmonic nanostructures. Herein, we
      adopt surface-enhanced elastic scattering as a SERS internal standard. Both
      elastic and inelastic (i.e., Raman) scattering are simultaneously enhanced by a
      given "hot spot", and thus, the surface-enhanced elastic scattering signal
      provides a localized intrinsic internal standard that scales across all of the
      plasmon-enhanced electromagnetic fields within a substrate. Elastically scattered
      light originates from the amplified spontaneous emission (ASE) of the commercial
      laser, leading to the formation of a low-wavenumber pseudo band that arises from
      the interaction of the ASE and the edge filter. A theoretical model was developed
      to illustrate the underlying mechanism supporting this normalization approach.
      The normalized Raman signals are independent of the incident laser intensity and
      the density of "hot spots" for numerous SERS substrates. Following "hot-spot"
      (HS) normalization, the coefficient of variation for the tested SERS substrates
      decreases from 10 to 60% to 2%-7%. This approach significantly improves SERS
      quantitation of four chloroanilines and enables collection of highly reproducible
      analyte adsorption results under both static and dynamic imaging conditions.
      Overall, this approach provides a simple means to improve SERS reproducibility
      without the need to use additional chemicals as internal standards.

PMID- 29356520
TI  - Cysteine-Derived Pleurotin Congeners from the Nematode-Trapping Basidiomycete
      Hohenbuehelia grisea.
AB  - The discovery of a Hohenbuehelia grisea specimen during a field trip in Northern
      Thailand led to the isolation and identification of three novel sulfur-bearing
      derivatives of dihydropleurotinic acid (4). Thiopleurotinic acid A (1) was
      established by the interpretation of spectral data (HRESIMS, 2D-NMR) as a 2
      hydroxy-3-mercaptopropanoic acid conjugate of dihydropleurotinic acid.
      Thiopleurotinic acid B (2) was shown to be the N-acetylcysteine conjugate of 4. A
      third compound (3) was established as a thiazole-containing derivative. Through
      feeding experiments with [U-13C3, 15N]-l-cysteine the formation of all three
      metabolites was shown to involve cysteine condensation with 4. The decreased
      cytotoxicity and antimicrobial activities of the new derivatives 1-3, compared to
      the parent compound 4, indicate a possible detoxification pathway of filamentous
      fungi.

PMID- 29356522
TI  - Kinetics of Inactivation of Waterborne Enteric Viruses by Ozone.
AB  - Ozone is an effective disinfectant against all types of waterborne pathogens.
      However, accurate and quantitative kinetic data regarding virus inactivation by
      ozone are scarce, because of the experimental challenges associated with the high
      reactivity of ozone toward viruses. Here, we established an experimental batch
      system that allows tailoring and quantifying of very low ozone exposures and
      simultaneously measuring virus inactivation. Second-order ozone inactivation rate
      constants (kO3-virus) of five enteric viruses [laboratory and two environmental
      strains of coxsackievirus B5 (CVF, CVEnv1, and CVEnv2), human adenovirus (HAdV),
      and echovirus 11 (EV)] and four bacteriophages (MS2, Qbeta, T4, and Phi174) were
      measured in buffered solutions. The kO3-virus values of all tested viruses ranged
      from 4.5 * 105 to 3.3 * 106 M-1 s-1. For MS2, kO3-MS2 depended only weakly on
      temperature (2-22  degrees C; Ea = 22.2 kJ mol-1) and pH (6.5-8.5), with an
      increase in kO3-MS2 with increasing pH. The susceptibility of the selected
      viruses toward ozone decreases in the following order: Qbeta > CVEnv2 > EV ~ MS2
      > Phi174 ~ T4 > HAdV > CVF ~ CVEnv1. On the basis of the measured kO3-Virus and
      typical ozone exposures applied in water and wastewater treatment, we conclude
      that ozone is a highly effective disinfectant for virus control.

PMID- 29356521
TI  - Differential Partitioning of Triterpenes and Triterpene Esters in Apple Peel.
AB  - Apple peel is a rich source of secondary metabolites, and several studies have
      outlined the dietary health benefits of ursane-type triterpenes in apple. Changes
      in triterpene metabolism have also been associated with the development of
      superficial scald, a postharvest apple peel browning disorder, and postharvest
      applications of diphenylamine and 1-methylcyclopropene. Previously, studies have
      generated metabolite profiles for whole apple peel or apple wax. In this study,
      we report separate metabolic analyses of isolated wax fractions and peel
      epidermis to investigate the spatial distribution of secondary metabolites in
      peel. In addition to examining previously reported triterpenes, we identified
      several unreported fatty acid esters of ursane-type triterpenes (C14-C22). All
      free pentacyclic triterpenes and triterpenic acids, with the exception of beta
      amyrin, were localized in the wax layer, along with esters of ursolic acid and
      uvaol. All sterols, sterol derivatives and alpha-amyrin esters were localized in
      the dewaxed peel epidermis.

PMID- 29356523
TI  - Structural Transformation of Birnessite by Fulvic Acid under Anoxic Conditions.
AB  - The structure and Mn(III) concentration of birnessite dictate its reactivity and
      can be changed by birnessite partial reduction, but effects of pH and
      reductant/birnessite ratios on the changes by reduction remain unclear. We found
      that the two factors strongly affect the structure of birnessite (delta-MnO2) and
      its Mn(III) content during its reduction by fulvic acid (FA) at pH 4-8 and
      FA/solid mass ratios of 0.01-10 under anoxic conditions over 600 h. During the
      reduction, the structure of delta-MnO2 is increasingly accumulated with both
      Mn(III) and Mn(II) but much more with Mn(III) at pH 8, whereas the accumulated Mn
      is mainly Mn(II) with little Mn(III) at pH 4 and 6. Mn(III) accumulation, either
      in layers or over vacancies, is stronger at higher FA/solid ratios. At FA/solid
      ratios >=1 and pH 6 and 8, additional hausmannite and MnOOH phases form. The
      altered birnessite favorably adsorbs FA because of the structural accumulation of
      Mn(II, III). Like during microbially mediated oxidative precipitation of
      birnessite, the dynamic changes during its reduction are ascribed to the
      birnessite-Mn(II) redox reactions. Our work suggests low reactivity of birnessite
      coexisting with organic matter and severe decline of its reactivity by partial
      reduction in alkaline environment.

PMID- 29356524
TI  - Weighted Averaging Scheme and Local Atomic Descriptor for pKa Prediction Based on
      Density Functional Theory.
AB  - As a continuation of our work on developing a density functional theory-based pKa
      predictor, we present conceptual improvements to our previously published shell
      model, which is a hierarchical organization of pKa training sets and which, in
      principle, covers all chemical space. The improvements concern the way the
      studied chemical compound is associated with the data points from the training
      sets. By introducing a new descriptor of the local atomic environment which
      foregoes dependence on chemical bonding and connectivity, we are able to
      automatically locate molecules from the training set that are most relevant to
      the proton dissociation equilibrium under study. This new scheme leads to the
      prediction of a single pKa value weighted across multiple training sets and thus
      patches a defect disclosed in the formulation of our previous model. Using the
      new parametrization approach, the pKa prediction gets rid of outliers reported in
      previous applications of our approach, eliminates ambiguity in interpreting the
      results, and improves the overall accuracy. Our new treatment accounts for
      multiple conformations both on the level of energetics and parametrization.
      Illustrative results are shown for several types of chemical structures
      containing guanidine, amidine, amine, and phenol functional groups, and which are
      representative of practically important large and flexible drug-like molecules.
      Our method's performance is compared to the performance of other previously
      published pKa prediction methods. Further possible improvements to the
      organization of the training sets and the potential application of our new local
      atomic descriptor to other kinds of parametrizations are discussed.

PMID- 29356525
TI  - Direct and Sequential Two-Photon Double Ionization of Two-Electron Quantum Dots.
AB  - In this work we study the double ionization yields and kinetic energy spectra of
      a two-electron spherical quantum dot (QD) exposed in laser fields. The
      theoretical description is based on an ab initio nonperturbative configuration
      interaction theory capable of describing the two-electron QD dynamics in THz and
      mid-IR ultrashort laser fields. The QD's confinement potential is approximated to
      have a Gaussian-like spatial dependence. We have found that significant
      variations of the two-electron kinetic energy patterns and two-photon double
      ionization yields occur as we vary the QD's size. For a given laser pulse, the
      double ionization yield increases by orders of magnitude when the dot size is
      reduced. The size of the QD determines the sequential or direct character of the
      two-photon double ionization process. Provided that it is energetically allowed,
      the sequential two-photon double ionization process, requiring minimal
      interelectronic correlations, becomes dominant over the direct one. In the
      sequential regime, the corresponding two-electron kinetic energy spectrum changes
      from a broadened single-peaked to a doubly peaked one. Moreover, we also have
      identified features in the spectrum that are distinctively different than those
      in its atomic counterpart.

PMID- 29356526
TI  - Quantum-Chemical Modeling of the First Steps of the Strecker Synthesis: From the
      Gas-Phase to Water Solvation.
AB  - The two first steps of the Strecker synthesis of glycine, namely (a) addition of
      ammonia to formaldehyde to give aminomethanol and (b) its dehydration leading to
      methaneimine, is studied using high level quantum chemistry computations (G3B3).
      Water solvation is modeled by considering the effect of adding a discrete number
      of active or passive molecules of water (up to four) and by immersing the
      identified water-solute complexes in a conductor-like polarizable continuum
      solvent model. Activation of the reactants by protonation is also examined.
      Exhaustive search of microhydrated neutral and protonated aminomethanol has been
      performed using a combination of hierarchical and genealogical approaches.
      Critical energies associated with all the elementary reaction steps were
      estimated using the accurate G3B3 composite method thus providing benchmarks to
      discuss the possible occurrence of Strecker synthesis in prebiotic chemistry.

PMID- 29356527
TI  - Using Fluorescence Spectroscopy To Identify Milk from Grass-Fed Dairy Cows and To
      Monitor Its Photodegradation.
AB  - Owing to its high omega-3 fatty acid content, milk from grass-fed dairy cows is
      becoming increasingly more attractive to consumers. Consequently, it is important
      to identify the origins of such products and to measure their content, at least
      relative to some standard. To date, chromatography has been the most extensively
      used technique. Sample preparation and cost, however, often reduce its widespread
      applicability. Here, we report the effectiveness of fluorescence spectroscopy for
      such quantification by measuring the amount of chlorophyll metabolites in the
      sample. Their content is significantly higher for milk from grass-fed cows
      compared to milk from grain/silage-fed cows. It is 0.11-0.13 MUM in milk samples
      from grass-fed cows, whereas in milk from cows fed grain/silage rations, the
      concentration was 0.01-0.04 MUM. In various organic milk samples, the chlorophyll
      metabolite concentration was in the range of 0.07-0.09 MUM. In addition, we
      explored the mechanisms of photodegradation of milk. Riboflavin and chlorophyll
      metabolites act as photosensitizers in milk for type-I and type-II reactions,
      respectively. It was also observed that the presence of high levels of
      chlorophyll metabolites can synergistically degrade riboflavin, contributing to
      the degradation of milk quality.

PMID- 29356528
TI  - Structural Characterization and Function Prediction of Immunoglobulin-like Fold
      in Cell Adhesion and Cell Signaling.
AB  - Domains that belong to an immunoglobulin (Ig) fold are extremely abundant in cell
      surface receptors, which play significant roles in cell-cell adhesion and
      signaling. Although the structures of domains in an Ig fold share common topology
      of beta-barrels, functions of receptors in adhesion and signaling are regulated
      by the very heterogeneous binding between these domains. Additionally, only a
      small number of domains are directly involved in the binding between two
      multidomain receptors. It is challenging and time consuming to experimentally
      detect the binding partners of a given receptor and further determine which
      specific domains in this receptor are responsible for binding. Therefore, current
      knowledge in the binding mechanism of Ig-fold domains and their impacts on cell
      adhesion and signaling is very limited. A bioinformatics study can shed light on
      this topic from a systematic point of view. However, there is so far no
      computational analysis on the structural and functional characteristics of the
      entire Ig fold. We constructed nonredundant structural data sets for all domains
      in Ig fold, depending on their functions in cell adhesion and signaling. We found
      that data sets of domains in adhesion receptors show different binding preference
      from domains in signaling receptors. Using structural alignment, we further built
      a common structural template for each group of a domain data set. By mapping the
      protein-protein binding interface of each domain in a group onto the surface of
      its structural template, we found binding interfaces are highly overlapped within
      each specific group. These overlapped interfaces, we called consensus binding
      interfaces, are distinguishable among different data sets of domains. Finally,
      the residue compositions on the consensus interfaces were used as indicators for
      multiple machine learning algorithms to predict if they can form homotypic
      interactions with each other. The overall performance of the cross-validation
      tests shows that our prediction accuracies ranged between 0.6 and 0.8.

PMID- 29356529
TI  - Static and Dynamic Mechanical Characteristics of Ionic Liquid Modified MWCNT-SBR
      Composites: Theoretical Perspectives for the Nanoscale Reinforcement Mechanism.
AB  - Well-dispersed, robust, mechanicaly long-term stable functionalized multiwalled
      carbon nanotube (f-MWCNT)-styrene butadiene rubber (SBR) nanocomposites were
      fabricated via a melt mixing route with the assistance of ionic liquid as a
      dispersing agent. The mechanical properties of f-MWCNT/SBR vulcanizates were
      compared over a range of loadings, and it was found that the network morphology
      was highly favorable for mechanical performance with enlarged stiffness. A
      comparative investigation of composite models found that modified Kelly-Tyson
      theory gave an excellent fit to tensile strength data of the composites
      considering the effect of the interphase between polymer and f-MWCNT. Dynamic
      mechanical analysis highlighted the mechanical reinforcement due to the improved
      filler-polymer interactions which were the consequence of proper dispersion of
      the nanotubes in the SBR matrix. Effectiveness of filler, entanglement density,
      and adhesion factor were evaluated to get an in depth understanding of the
      reinforcing mechanism of modified MWCNT. The amount of polymer chains immobilized
      by the filler surface computed from dynamic mechanical analysis further supports
      a substantial boost up in mechanics. The Cole-Cole plot shows an imperfect
      semicircular curve representing the heterogeneity of the system and moderately
      worthy filler polymer bonding. The combined results of structural
      characterizatrion by Raman spectroscopy, cure characteristics, mechanical
      properties, and scanning and transmission electron microscopy (SEM, TEM) confirm
      the role of ionic liquid modified MWCNT as a reinforcing agent in the present
      system.

PMID- 29356530
TI  - Probing the Ionic Atmosphere and Hydration of the c-MYC i-Motif.
AB  - G-quadruplexes and i-motifs are noncanonical secondary structures of DNA that
      appear to play a number of regulatory roles in the genome with clear connection
      to disease. Characterization of the forces stabilizing these structures is
      necessary for developing an ability to induce G-quadruplex and/or i-motif
      structures at selected genomic loci in a controlled manner. We report here the
      results of pH-dependent acoustic and densimetric measurements and UV melting
      experiments at elevated pressures to scrutinize changes in hydration and ionic
      atmosphere accompanying i-motif formation by the C-rich DNA sequence from the
      promoter region of the human c-MYC oncogene [5'-d(TTACCCACCCTACCCACCCTCA)] (ODN).
      We also conducted pH-dependent acoustic and densimetric characterizations of two
      DNA molecules that are compositionally identical to ODN but do not adopt the i
      motif conformation, 5'-d(CTCTCACCACACCACACCTCTC) (ODN1) and 5'
      d(CACACTCCTCACCTCTCCACAC) (ODN2). Our results reveal that i-motif formation by
      ODN is not accompanied by changes in volume and compressibility. The volumetric
      similarity of the i-motif and coil states of ODN implies a fortuitous
      compensation between changes in the intrinsic and hydration contributions to
      volume and compressibility. Analysis of the pH-dependent volumetric profiles of
      ODN, ODN1, and ODN2, along with the data on volumetric changes accompanying the
      protonation of isolated cytosine and deoxycytidine, suggests that protonation of
      the cytosines in the oligonucleotides causes release of the majority if not all
      of their counterions to the bulk. Thus, in the i-motif conformation, the oligomer
      no longer acts as a polyelectrolyte insofar as counterions are concerned. We
      discuss the biological ramifications of our results.

PMID- 29356531
TI  - Signatures of a Conical Intersection in Adiabatic Dissociation on the Ground
      Electronic State.
AB  - Conical intersections are known to cause nonadiabatic transitions, but their
      effects on adiabatic dynamics are often ignored. Using the overtone-induced
      dissociation of the hydroxymethyl radical as an example, we demonstrate that
      ground-state O-H bond rupture is significantly affected by a conical intersection
      with an electronically excited state along the dissociation path, despite the
      much lower energy of the dissociating state than that of the conical
      intersection. In addition to lifetime differences, the geometric phase leads to a
      different H2CO rotational state distribution compared with that obtained using
      the standard single-state adiabatic model, which constitutes a signature of the
      conical intersection.

PMID- 29356533
TI  - Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic
      Tertiary Amides: A Synthetic and Mechanistic Study.
AB  - An efficient synthesis has been developed for the preparation of 9H-pyrrolo[1,2
      a]indol-9-ones (fluorazones) from readily available anthranilic acid derivatives
      via a one-pot amide- and pyrrole-formation step, followed by an intramolecular
      cyclodehydration. The cyclodehydration process is mediated by the activation of
      aromatic tertiary amides by triflic anhydride (Tf2O). Comparison of various benzo
      substituents is shown to demonstrate the high functional group tolerance of this
      transformation. In addition, study of the reaction mechanism is also presented to
      unfold the exact role of the applied base additive. Herein, as a first example,
      we report our findings that Tf2O-mediated amide activation is obstructed by the
      easy protonation of amides by the formed triflic acid during the activation step.
      Additionally, it has been also proven that the base additive is not involved in
      the transformation of O-triflyliminium triflates into reactive species (e.g.,
      nitrilium triflates) and is only responsible to neutralize the superacid to avoid
      the protonation of both the secondary or tertiary amides.

PMID- 29356534
TI  - Anharmonic Rovibrational Partition Functions for Fluxional Species at High
      Temperatures via Monte Carlo Phase Space Integrals.
AB  - Monte Carlo phase space integration (MCPSI) is used to compute full dimensional
      and fully anharmonic, but classical, rovibrational partition functions for 22
      small- and medium-sized molecules and radicals. Several of the species considered
      here feature multiple minima and low-frequency nonlocal motions, and efficiently
      sampling these systems is facilitated using curvilinear (stretch, bend, and
      torsion) coordinates. The curvilinear coordinate MCPSI method is demonstrated to
      be applicable to the treatment of fluxional species with complex rovibrational
      structures and as many as 21 fully coupled rovibrational degrees of freedom.
      Trends in the computed anharmonicity corrections are discussed. For many systems,
      rovibrational anharmonicities at elevated temperatures are shown to vary
      consistently with the number of degrees of freedom and with temperature once
      rovibrational coupling and torsional anharmonicity are accounted for. Larger
      corrections are found for systems with complex vibrational structures, such as
      systems with multiple large-amplitude modes and/or multiple minima.

PMID- 29356535
TI  - Identification of a Novel Positron Emission Tomography (PET) Ligand for Imaging
      beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE-1) in Brain.
AB  - Alzheimer's disease (AD) is characterized by accumulation of beta-amyloid (Abeta)
      plaques and neurofibrillary tau tangles in the brain. beta-Site amyloid precursor
      protein cleaving enzyme 1 (BACE1) plays a key role in the generation of Abeta
      fragments via extracellular cleavage of the amyloid precursor protein (APP). We
      became interested in developing a BACE1 PET ligand to facilitate clinical
      assessment of BACE1 inhibitors and explore its potential in the profiling and
      selection of patients for AD trials. Using a set of PET ligand design parameters,
      compound 3 (PF-06684511) was rapidly identified as a lead with favorable in vitro
      attributes and structural handles for PET radiolabeling. Further evaluation in an
      LC-MS/MS "cold tracer" study in rodents revealed high specific binding to BACE1
      in brain. Upon radiolabeling, [18F]3 demonstrated favorable brain uptake and high
      in vivo specificity in nonhuman primate (NHP), suggesting its potential for
      imaging BACE1 in humans.

PMID- 29356532
TI  - Targeting Multiple Effector Pathways in Pancreatic Ductal Adenocarcinoma with a G
      Quadruplex-Binding Small Molecule.
AB  - Human pancreatic ductal adenocarcinoma (PDAC) involves the dysregulation of
      multiple signaling pathways. A novel approach to the treatment of PDAC is
      described, involving the targeting of cancer genes in PDAC pathways having over
      representation of G-quadruplexes, using the trisubstituted naphthalene diimide
      quadruplex-binding compound 2,7-bis(3-morpholinopropyl)-4-((2-(pyrrolidin-1
      yl)ethyl)amino)benzo[ lmn][3,8]phenanthroline-1,3,6,8(2 H,7 H)-tetraone (CM03).
      This compound has been designed by computer modeling, is a potent inhibitor of
      cell growth in PDAC cell lines, and has anticancer activity in PDAC models, with
      a superior profile compared to gemcitabine, a commonly used therapy. Whole
      transcriptome RNA-seq methodology has been used to analyze the effects of this
      quadruplex-binding small molecule on global gene expression. This has revealed
      the down-regulation of a large number of genes, rich in putative quadruplex
      elements and involved in essential pathways of PDAC survival, metastasis, and
      drug resistance. The changes produced by CM03 represent a global response to the
      complexity of human PDAC and may be applicable to other currently hard-to-treat
      cancers.

PMID- 29356536
TI  - Phase Behavior of Ammonium Sulfate with Organic Acid Solutions in Aqueous Aerosol
      Mimics Using Microfluidic Traps.
AB  - Water-soluble organic acids such as dicarboxylic acids are known to form a
      significant fraction of organic aerosol mass, yet the chemical composition and
      interactions between components in an organic acid-inorganic salt mixed particle
      remain unclear. In this study, phase behavior of different mixing ratios of the
      salt and organic acids, here 3-methyl glutaric acid and 3-methyl adipic acid, are
      investigated with respect to their water activity. A microfluidic pervaporation
      approach is used to study different phase transitions of internally mixed aqueous
      droplets. Single droplets of varied compositions are trapped and stored in
      microfluidic wells until dehydration, where both the water content and the
      solution volume of the droplet decrease slowly with time. The volume is
      calculated by imaging techniques and correlated with the initial known
      concentration of the solution to determine concentrations at each time interval.
      The phase transitions of the droplets with changing concentrations are also
      observed under an inverted microscope. This study will help determine the
      concentration at which a mixture droplet, mimicking organic and inorganic
      atmospheric aerosols, changes phase.

PMID- 29356537
TI  - Salt Sensitivity of the Thermoresponsive Behavior of PNIPAAm Brushes.
AB  - We report investigations on the salt sensitivity of the thermoresponsive behavior
      of PNIPAAm brushes applying the quartz crystal microbalance coupled with
      spectroscopic ellipsometry technique. This approach enables a detailed study of
      the optical and mechanical behavior of the polymer coatings. Additional
      conclusions can be drawn from the difference between both techniques due to a
      difference in the contrast mechanism of both methods. A linear shift of the phase
      transition temperature to lower temperatures with the addition of sodium chloride
      was found, similar to the behavior of free polymer chains in solution. The
      thermal hysteresis was found to be decreased by the addition of sodium chloride
      to the solution, hinting to the interaction of the ions with the amide groups of
      the polymer, whereby the formation of hydrogen bonds is hindered. The results of
      this study are of relevance to the application of PNIPAAm brushes in biological
      fluids and demonstrate the additional potential of the ion sensitivity besides
      the better known thermosensitivity.

PMID- 29356538
TI  - Ionic-Liquid-Infused Nanostructures as Repellent Surfaces.
AB  - In order to prepare lubricant-infused repellent coatings on silica nanostructures
      using low vapor pressure ionic liquids as lubricants, we study the wetting
      behavior of a set of imidazolium-based ionic liquids with different alkyl side
      chains as a function of the applied surface functionalities. We take advantage of
      the structural color of inverse opals prepared from a colloidal coassembly
      technique to study the infiltration of ionic liquids into these nanoporous
      structures. We find that the more hydrophobic ionic liquids with butyl and hexyl
      side chains can completely infiltrate inverse opals functionalized with mixed
      self-assembled monolayers composed of imidazole groups and aliphatic hydrocarbon
      chains, which we introduce via silane chemistry. These molecular species reflect
      the chemical nature of the ionic liquid, thereby increasing the affinity between
      the liquid and solid surface. The mixed surface chemistry provides sufficiently
      small contact angles with the ionic liquid to infiltrate the nanopores while
      maximizing the contact angle with water. As a result, the mixed monolayers enable
      the design of a stable ionic liquid/solid interface that is able to repel water
      as a test liquid. Our results underline the importance of matching chemical
      affinities to predict and control the wetting behavior in complex, multiphase
      systems.

PMID- 29356539
TI  - Curcumin: An Effective or Deceptive Dietary Factor? Challenges for Functional
      Food Scientists.

PMID- 29356540
TI  - Unravelling the Role of an Aqueous Environment on the Electronic Structure and
      Ionization of Phenol Using Photoelectron Spectroscopy.
AB  - Water is the predominant medium for chemistry and biology, yet its role in
      determining how molecules respond to ultraviolet light is not well understood at
      the molecular level. Here, we combine gas-phase and liquid-microjet photoelectron
      spectroscopy to investigate how an aqueous environment influences the electronic
      structure and relaxation dynamics of phenol, a ubiquitous motif in many
      biologically relevant chromophores. The vertical ionization energies of
      electronically excited states are important quantities that govern the rates of
      charge-transfer reactions, and, in phenol, the vertical ionization energy of the
      first electronically excited state is found to be lowered by around 0.8 eV in
      aqueous solution. The initial relaxation dynamics following photoexcitation with
      ultraviolet light appear to be remarkably similar in the gas-phase and aqueous
      solution; however, in aqueous solution, we find evidence to suggest that solvated
      electrons are formed on an ultrafast time scale following photoexcitation just
      above the conical intersection between the first two excited electronic states.

PMID- 29356541
TI  - Photoswitching an Isolated Donor-Acceptor Stenhouse Adduct.
AB  - Donor-acceptor Stenhouse adducts (DASAs) are a new class of photoswitching
      molecules with excellent fatigue resistance and synthetic tunability. Here,
      tandem ion mobility mass spectrometry coupled with laser excitation is used to
      characterize the photocyclization reaction of isolated, charge-tagged DASA
      molecules over the 450-580 nm range. The experimental maximum response at 530 nm
      agrees with multireference perturbation theory calculations for the S1 <- S0
      transition maximum at 533 nm. Photocyclization in the gas phase involves
      absorption of at least two photons; the first photon induces Z-E isomerization
      from the linear isomer to metastable intermediate isomers, while the second
      photon drives another E-Z isomerization and 4pi-electrocyclization reaction.
      Cyclization is thermally reversible in the gas phase with collisional excitation.

PMID- 29356542
TI  - Ultrafast Tailoring of Carbon Surfaces via Electrochemically Attached
      Triazolinediones.
AB  - The straightforward coupling between a triazolinedione (TAD) unit and citronellyl
      derivatives via an Alder-ene reaction has been exploited to tailor the
      physicochemical surface properties of glassy carbon (GC) surfaces in an ultrafast
      and additive-free manner. For this purpose, we first covalently grafted a TAD
      precursor onto GC via electrochemical reduction of an in situ generated diazonium
      salt, which was then electrochemically oxidized into the desired GC-bonded TAD
      unit. A kinetic study of the modification of this reactive layer with an
      electroactive ferrocene probe proved that a complete functionalization was
      obtained in merely 1 minute. Further modification experiments with a fluorinated
      probe demonstrated that the surface properties can be swiftly tailored on demand.
      The different modification steps, as well as the efficiency of this strategy,
      were investigated by electrochemistry, contact angle goniometry, and X-ray
      photoelectron spectroscopy analysis.

PMID- 29356543
TI  - Site-Specifically Labeled Antibody-Drug Conjugate for Simultaneous Therapy and
      ImmunoPET.
AB  - The conjugation of antibodies with cytotoxic drugs can alter their in vivo
      pharmacokinetics. As a result, the careful assessment of the in vivo behavior,
      and specifically the tumor-targeting properties, of antibody-drug conjugates
      represents a crucial step in their development. In order to facilitate this
      process, we have created a methodology that facilitates the dual labeling of an
      antibody with both a toxin and a radionuclide for positron emission tomography
      (PET). To minimize the impact of these modifications, this chemoenzymatic
      approach leverages strain-promoted azide-alkyne click chemistry to graft both
      cargoes to the heavy chain glycans of the immuoglobulin's Fc domain. As a proof
      of-concept, a HER2-targeting trastuzumab immunoconjugate was created bearing both
      a monomethyl auristatin E (MMAE) toxin as well as the long-lived positron
      emitting radiometal 89Zr ( t1/2 ~ 3.3 days). Both the tumor targeting and
      therapeutic efficacy of the 89Zr-trastuzumab-MMAE immunoconjugate were validated
      in vivo using a murine model of HER2-expressing breast cancer. The site
      specifically dual-labeled construct enabled the clear visualization of tumor
      tissue via PET imaging, producing tumoral uptake of ~70%ID/g. Furthermore, a
      longitudinal therapy study revealed that the immunoconjugate exerts significant
      antitumor activity, leading to a >90% reduction in tumor volume over the course
      of 20 days.

PMID- 29356544
TI  - Effect of Concentration on the Interfacial and Bulk Structure of Ionic Liquids in
      Aqueous Solution.
AB  - Bio and aqueous applications of ionic liquids (IL) such as catalysis in micelles
      formed in aqueous IL solutions or extraction of chemicals from biologic materials
      rely on surface-active and self-assembly properties of ILs. Here, we discuss
      qualitative relations of the interfacial and bulk structuring of a water-soluble
      surface-active IL ([C8MIm][Cl]) on chemically controlled surfaces over a wide
      range of water concentrations using both force probe and X-ray scattering
      experiments. Our data indicate that IL structuring evolves from surfactant-like
      surface adsorption at low IL concentrations, to micellar bulk structure
      adsorption above the critical micelle concentration, to planar bilayer formation
      in ILs with <1 wt % of water and at high charging of the surface. Interfacial
      structuring is controlled by mesoscopic bulk structuring at high water
      concentrations. Surface chemistry and surface charges decisively steer
      interfacial ordering of ions if the water concentration is low and/or the surface
      charge is high. We also demonstrate that controlling the interfacial forces by
      using self-assembled monolayer chemistry allows tuning of interfacial structures.
      Both the ratio of the head group size to the hydrophobic tail volume as well as
      the surface charging trigger the bulk structure and offer a tool for predicting
      interfacial structures. Based on the applied techniques and analyses, a
      qualitative prediction of molecular layering of ILs in aqueous systems is
      possible.

PMID- 29356545
TI  - Glutaredoxin-1 Silencing Induces Cell Senescence via p53/p21/p16 Signaling Axis.
AB  - Glutaredoxin-1 (Grx1) catalyzes deglutathionylation with glutathione as a
      cofactor. Accumulating evidence indicates important roles for Grx1 and S
      glutathionylation in the aging process; however, further exploration of Grx1
      regulated cellular processes is important to understand the functions of Grx1 in
      aging. In the present study, we constructed stable Grx1 knockdown or
      overexpression human cell lines. Grx1 silencing significantly decreased the
      cellular ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG)
      (GSH/GSSG ratio), resulting in excessive reactive oxygen species (ROS)
      accumulation, whereas Grx1 overexpression decreased cellular ROS levels. Grx1
      silencing also increased glutathionylation of DJ-1 and HSP60, contributing to
      decreased mitochondrial spare respiration capacity and ATP production. We applied
      quantitative proteomics to identify differentially expressed proteins between
      Grx1 knockdown and control cells and showed that Grx1 silencing inactivated DNA
      replication and damage repair pathways. p53 signaling was activated by Grx1
      silencing, which inhibited the CDK4-mediated G1-S transition, resulting in G1
      phase cell-cycle arrest and cell senescence, a known hallmark of aging. Taken
      together, our results indicate that Grx1 regulates DNA replication and damage
      repair processes and is a potential therapeutic target for aging-related
      diseases.

PMID- 29356546
TI  - Impact of the Formulation Pathway on the Colloidal State and Crystallinity of
      Poly-epsilon-caprolactone Particles Prepared by Solvent Displacement.
AB  - The formulation pathway and/or the mixing method are known to be relevant in many
      out-of-equilibrium processes. In this work, we studied the effect of the mixing
      conditions on the physicochemical properties of poly-epsilon-caprolactone (PCL)
      particles prepared by solvent displacement. More specifically, water was added in
      one shot (fast addition) or drop by drop to PCL solution in tetrahydrofuran (THF)
      to study the impact of the mixing process on particle properties including size,
      stability, and crystallinity. Two distinct composition maps representing the Ouzo
      domain characteristic of the presence of metastable nanoparticles have been
      established for each mixing method. Polymer nanoparticles are formed in the Ouzo
      domain according to a nucleation and growth (or aggregation) mechanism. The fast
      addition promotes a larger nucleation rate, thus favoring the formation of small
      and uniform particles. For the drop-by-drop addition, for which the polymer
      solubility gradually decreases, the composition trajectories systematically cross
      an intermediate unstable region between the solubility limit of the polymer and
      the Ouzo domain. This leads to heterogeneous nucleation as shown by the formation
      of larger and less stable particles. Particles formed in the Ouzo domain have
      semi-crystalline properties. The PCL melting point is decreased with the THF
      fraction trapped in particles in accordance with Flory's theory for melt
      crystallization. On the other hand, the degree of crystallinity is constant,
      around 20% regardless of the THF fraction. No difference between fast and slow
      addition could be detected on the semi-crystalline properties of the particles
      which emphasize that thermodynamic rather than kinetic factors drive the polymer
      crystallization in particles. The recovery of bulk PCL crystallinity after the
      removal of THF from particles tends to confirm this hypothesis.

PMID- 29356547
TI  - Exploring Biological and Geological Age-related Changes through Variations in
      Intra- and Intertooth Proteomes of Ancient Dentine.
AB  - Proteomic analyses are becoming more widely used in archeology not only due to
      the greater preservation of proteins in ancient specimens than DNA but also
      because they can offer different information, particularly relating to
      compositional preservation and potentially a means to estimate biological and
      geological age. However, it remains unclear to what extent different burial
      environments impact these aspects of proteome decay. Teeth have to date been much
      less studied than bone but are ideal to explore how proteins decay with time due
      to the negligible turnover that occurs in dentine relative to bone. We
      investigated the proteome variability and deamidation levels of different
      sections of molar teeth from archeological bovine mandibles as well as their
      mandibular bone. We obtained a greater yield of proteins from the crown of the
      teeth but did not find differences between the different molars analyzed within
      each mandible. We also obtained the best variety of protein from a well-preserved
      mandible that was not the youngest one in terms of chronological age, showing the
      influence of the preservation conditions on the final proteomic outcome.
      Intriguingly, we also noticed an increase in abundance levels of fetuin-A in
      biologically younger mandibles as reported previously, but the opposite trend in
      tooth dentine. Interestingly, we observed higher glutamine deamidation levels in
      teeth from the geologically oldest mandible despite it being the biologically
      youngest specimen, showing that the archeological age strongly impacts on the
      level of deamidations observed, much more so than biological aging. This
      indicates that the glutamine deamidation ratio of selected peptides may act as a
      good predictor of the relative geochronological age of archeological specimens.

PMID- 29356548
TI  - Thermoplasmonic Ignition of Metal Nanoparticles.
AB  - Explosives, propellants, and pyrotechnics are energetic materials that can store
      and quickly release tremendous amounts of chemical energy. Aluminum (Al) is a
      particularly important fuel in many applications because of its high energy
      density, which can be released in a highly exothermic oxidation process. The
      diffusive oxidation mechanism (DOM) and melt-dispersion mechanism (MDM) explain
      the ways powders of Al nanoparticles (NPs) can burn, but little is known about
      the possible use of plasmonic resonances in NPs to manipulate photoignition. This
      is complicated by the inhomogeneous nature of powders and very fast heating and
      burning rates. Here, we generate Al NPs with well-defined sizes, shapes, and
      spacings by electron beam lithography and demonstrate that their plasmonic
      resonances can be exploited to heat and ignite them with a laser. By combining
      simulations with thermal-emission, electron-, and optical-microscopy studies, we
      reveal how an improved control over NP ignition can be attained.

PMID- 29356549
TI  - Reversibly Switching Wormlike Micelles Formed by a Selenium-Containing Surfactant
      and Benzyl Tertiary Amine Using CO2/N2 and Redox Reaction.
AB  - Multiresponsive wormlike micelles (WLMs) remain a significant challenge in the
      construction of smart soft materials based on surfactants. Herein, we report the
      preparation of a viscoelastic wormlike micellar solution based on a new redox
      responsive surfactant, sodium dodecylselanylpropyl sulfate (SDSePS), and
      commercially available benzyl tertiary amine (BTA) in the presence of CO2. In
      this system, SDSePS can be reversibly switched on (selenide) and off (selenoxide)
      by a redox reaction, akin to that previously reported for benzylselanyl or
      phenylselanyl surfactants. By alternately adding H2O2 and N2H4.H2O, WLMs can be
      reversibly broken and formed because of the transformation of the hydrophilic
      headgroup of SDSePS, originating from the reversible formation of selenoxide.
      Moreover, WLMs can also be switched on and off by cyclically bubbling CO2 and N2
      because of the variation of the binding interaction between SDSePS and BTA,
      resulting from the reversible protonation of BTA. This interesting and unique
      multiresponsive behavior makes the current WLMs a potential candidate for smart
      control of the "sol-gel" transition or substantial thickening of solutions.

PMID- 29356550
TI  - Operando Monitoring of the Solution-Mediated Discharge and Charge Processes in a
      Na-O2 Battery Using Liquid-Electrochemical Transmission Electron Microscopy.
AB  - Although in sodium-oxygen (Na-O2) batteries show promise as high-energy storage
      systems, this technology is still the subject of intense fundamental research,
      owing to the complex reaction by which it operates. To understand the formation
      mechanism of the discharge product, sodium superoxide (NaO2), advanced
      experimental tools must be developed. Here we present for the first time the use
      of a Na-O2 microbattery using a liquid aprotic electrolyte coupled with fast
      imaging transmission electron microscopy to visualize, in real time, the
      mechanism of NaO2 nucleation/growth. We observe that the formation of NaO2 cubes
      during reduction occurs by a solution-mediated nucleation process. Furthermore,
      we unambiguously demonstrate that the subsequent oxidation of NaO2 of which
      little is known also proceeds via a solution mechanism. We also provide insight
      into the cell electrochemistry via the visualization of an outer shell of
      parasitic reaction product, formed through chemical reaction at the interface
      between the growing NaO2 cubes and the electrolyte, and suggest that this process
      is responsible for the poor cyclability of Na-O2 batteries. The assessment of the
      discharge-charge mechanistic in Na-O2 batteries through operando electrochemical
      transmission electron microscopy visualization should facilitate the development
      of this battery technology.

PMID- 29356551
TI  - Exploration of the Smallest Diameter Tin Nanowires Achievable with
      Electrodeposition: Sub 7 nm Sn Nanowires Produced by Electrodeposition from a
      Supercritical Fluid.
AB  - Electrodeposition of Sn from supercritical difluoromethane has been performed
      into anodic alumina templates with pores down to 3 nm in diameter and into
      mesoporous silica templates with pores of diameter 1.5 nm. Optimized deposits
      have been characterized using X-ray diffraction, scanning electron microscopy,
      and scanning transmission electron microscopy (bright field, high-angle annular
      dark field, and energy-dispersive X-ray elemental mapping). Crystalline 13 nm
      diameter Sn nanowires have been electrodeposited in symmetric pore anodic
      alumina. Direct transmission electron microscopy evidence of sub 7 nm Sn
      nanowires in asymmetric anodic alumina has been obtained. These same measurements
      present indirect evidence for electrodeposition through 3 nm constrictions in the
      same templates. A detailed transmission electron microscopy study of mesoporous
      silica films after Sn deposition is presented. These indicate that it is possible
      to deposit Sn through the 1.5 nm pores in the mesoporous films, but that the
      nanowires formed are not stable. Suggestions of why this is the case and how such
      extreme nanowires could be stabilized are presented.

PMID- 29356552
TI  - Synthesis of Furo[2,3-b]pyran-2-ones through Ag(I)- or Ag(I)-Au(I)-Catalyzed
      Cascade Annulation of Alkynols and alpha-Ketoesters.
AB  - Ag(I)- or Ag(I)-Au(I)-catalyzed cascade annulation of alkynols (5-hexyn-1-ol
      systems) with alpha-ketoesters involving a dual activation process (pi and sigma)
      has been developed for the first time. This reaction proceeds through
      cycloisomerization of alkynol to give the 6-endo-enol ether followed by
      annulation with an alpha-ketoester to furnish furo[2,3-b]pyran-2-ones in good
      yields. Chemical structures of all products were rigorously confirmed by single
      crystal X-ray analysis and analogy.

PMID- 29356553
TI  - Formal Synthesis of (-)-Codeine by Application of Temporary Thio Derivatization.
AB  - Desymmetrization of a p-quinone monoacetal by organocatalytic sulfa-Michael
      addition provided rapid access to a C-ring building block for a formal synthesis
      of (-)-codeine. By means of a diastereoselective 1,2-addition for A/C-ring union,
      an intramolecular nitrone cycloaddition for construction of the phenanthrene
      core, and a sulfoxide elimination, an enantiopure key intermediate of the
      authors' previous synthesis of racemic codeine was available in 12 steps from
      isovanillin.

PMID- 29356554
TI  - Development of Software for Automatic Analysis of Intervention in the Field of
      Homeopathy.
AB  - OBJECTIVE: To study the effect of homeopathic medicines (in higher potencies) in
      normal subjects, Peripheral Pulse Analyzer (PPA) has been used to record
      physiologic variability parameters before and after administration of the
      medicine/placebo in 210 normal subjects. METHODS: Data have been acquired in
      seven rounds; placebo was administered in rounds 1 and 2 and medicine in
      potencies 6, 30, 200, 1 M, and 10 M was administered in rounds 3 to 7,
      respectively. Five different medicines in the said potencies were given to a
      group of around 40 subjects each. Although processing of data required human
      intervention, a software application has been developed to analyze the processed
      data and detect the response to eliminate the undue delay as well as human bias
      in subjective analysis. This utility named Automatic Analysis of Intervention in
      the Field of Homeopathy is run on the processed PPA data and the outcome has been
      compared with the manual analysis. The application software uses adaptive
      threshold based on statistics for detecting responses in contrast to fixed
      threshold used in manual analysis. RESULTS: The automatic analysis has detected
      12.96% higher responses than subjective analysis. Higher response rates have been
      manually verified to be true positive. This indicates robustness of the
      application software. The automatic analysis software was run on another set of
      pulse harmonic parameters derived from the same data set to study cardiovascular
      susceptibility and 385 responses were detected in contrast to 272 of variability
      parameters. It was observed that 65% of the subjects, eliciting response, were
      common. CONCLUSION: This not only validates the software utility for giving
      consistent yield but also reveals the certainty of the response. This development
      may lead to electronic proving of homeopathic medicines (e-proving).

PMID- 29356556
TI  - Treatment of Pulmonary Lymphangioleiomyomatosis during Pregnancy.

PMID- 29356555
TI  - Riboflavin Metabolism Variation among Clinical Isolates of Streptococcus
      pneumoniae Results in Differential Activation of Mucosal-associated Invariant T
      Cells.
AB  - Streptococcus pneumoniae is an important bacterial pathogen that causes a range
      of noninvasive and invasive diseases. The mechanisms underlying variability in
      the ability of S. pneumoniae to transition from nasopharyngeal colonization to
      disease-causing pathogen are not well defined. Mucosal-associated invariant T
      (MAIT) cells are prevalent in mucosal tissues such as the airways and are
      believed to play an important role in the early response to infection with
      bacterial pathogens. The ability of MAIT cells to recognize and contain infection
      with S. pneumoniae is not known. In the present study, we analyzed MAIT-cell
      responses to infection with clinical isolates of S. pneumoniae serotype 19A, a
      serotype linked to invasive pneumococcal disease. We found that although MAIT
      cells were capable of responding to human dendritic and airway epithelial cells
      infected with S. pneumoniae, the magnitude of response to different serotype 19A
      isolates was determined by genetic differences in the expression of the
      riboflavin biosynthesis pathway. MAIT-cell release of cytokines correlated with
      differences in the ability of MAIT cells to respond to and control S. pneumoniae
      in vitro and in vivo in a mouse challenge model. Together, these results
      demonstrate first that there are genetic differences in riboflavin metabolism
      among clinical isolates of the same serotype and second that these likely
      determine MAIT-cell function in response to infection with S. pneumoniae. These
      differences are critical when considering the role that MAIT cells play in early
      responses to pneumococcal infection and determining whether invasive disease will
      develop.

PMID- 29356557
TI  - The Practice of Respect in the ICU.
AB  - Although "respect" and "dignity" are intuitive concepts, little formal work has
      addressed their systematic application in the ICU setting. After convening a
      multidisciplinary group of relevant experts, we undertook a review of relevant
      literature and collaborative discussions focused on the practice of respect in
      the ICU. We report the output of this process, including a summary of current
      knowledge, a conceptual framework, and a research program for understanding and
      improving the practice of respect and dignity in the ICU. We separate our report
      into findings and proposals. Findings include the following: 1) dignity and
      respect are interrelated; 2) ICU patients and families are vulnerable to
      disrespect; 3) violations of respect and dignity appear to be common in the ICU
      and overlap substantially with dehumanization; 4) disrespect may be associated
      with both primary and secondary harms; and 5) systemic barriers complicate
      understanding and the reliable practice of respect in the ICU. Proposals include:
      1) initiating and/or expanding a field of research on the practice of respect in
      the ICU; 2) treating "failures of respect" as analogous to patient safety events
      and using existing quality and safety mechanisms for improvement; and 3)
      identifying both benefits and potential unintended consequences of efforts to
      improve the practice of respect. Respect and dignity are important considerations
      in the ICU, even as substantial additional research remains to be done.

PMID- 29356558
TI  - Computed tomographic evaluation of the thymus-does obesity affect thymic fatty
      involution in a healthy young adult population?
AB  - OBJECTIVE: To determine a relationship between increased body mass index (BMI)
      and fatty involution of the thymus in subjects aged between 20 and 30 years.
      METHODS: CT images of 94 patients aged between 20 and 30 years were reviewed.
      Quantitative thymic mean attenuation was recorded and qualitative thymic
      attenuation was assigned to 1 of 4 possible grades. BMI and subcutaneous fat
      thickness were documented. Correlations between thymic attenuation, and BMI and
      subcutaneous fat thickness were assessed using linear regression models.
      Differences in thymic attenuation in overweight vs normal weight patients were
      assessed using t-test and Pearson Chi2 analysis. RESULTS: Low mean thymic
      attenuation values were associated with higher patient BMI (p = 0.024). Normal
      weight patients had a mean quantitative thymic attenuation of 15.5 Hounsfield
      unit and overweight patients had a mean quantitative thymic attenuation of -16.4
      Hounsfield unit (p = 0.0218). There was a significant association between
      increasing subcutaneous fat thickness and reduced mean quantitative thymic
      attenuation (p < 0.0001). There was also a significant difference in subcutaneous
      fat thickness when comparing qualitatively assessed thymic Grade 0 with grades 2
      and 3 (p = 0.027 and 0.001 respectively); and Grade 1 with Grade 3 (p = 0.001).
      CONCLUSION: In patients between 20 and 30 years old, the degree of thymic fatty
      infiltration is related to BMI. Advances in knowledge: Multidetector CT can
      assess fatty involution of the thymus gland. This retrospective study
      demonstrates a relationship between BMI and thymus gland fatty involution.
      Subjects with increased subcutaneous fat have decreased mean thymus gland
      attenuation.

PMID- 29356559
TI  - Commemoration of Jack Fowler's life, work, impact and legacy.
AB  - Jack Fowler [formally Professor John Francis Fowler PhD, DSc, MD (Hon), FInstP,
      FRCR, FBIR, FAAPM, FASTRO, FACRO] was a remarkable scientist, known to many in
      the field of clinical radiation biology as at the forefront of applying linear
      quadratic dose-fractionation-time modelling to help improve a wide range of
      cancer treatments using radiotherapy. His death on 1st December 2016 after a long
      career of 60 years was marked by Obituaries in six scientific journals in his
      field e.g. 1 - 4 Jack is remembered for his quantification of biologically
      effective dose in a wide variety of radiotherapy practices and modified protocols
      (supported by experimental-system studies), his extensive publications, his
      didactic lecturing and teaching abilities, and his warm personality.

PMID- 29356560
TI  - Reply to Yanagisawa: Treatment of Pulmonary Lymphangioleiomyomatosis during
      Pregnancy.

PMID- 29356561
TI  - Using 24-Hour Weight as Reference for Weight Loss Calculation Reduces
      Supplementation and Promotes Exclusive Breastfeeding in Infants Born by Cesarean
      Section.
AB  - BACKGROUND AND OBJECTIVES: To promote exclusive breastfeeding, supplements are
      not recommended without medical indications such as clinical evidence of
      dehydration. Loss of >=10% of birth weight (BW) often triggers supplementation
      due to nursery staff's concern for dehydration. Studies have demonstrated that
      transplacental passage of maternal intrapartum intravenous fluids for anesthesia
      may inflate BW. Researchers have proposed using newborn's 24-hour weight (24HW),
      after fluid diuresis, as preferred reference for weight loss calculation. The
      mother-infant unit at Hartford Hospital, a Baby-Friendly Hospital, implemented
      this recommendation into routine practice in March 2014. This study was conducted
      to evaluate this practice change's safety and effectiveness in decreasing
      supplementation. METHODS: We performed a retrospective chart review on healthy
      full-term newborns delivered by C-section in 12 months before (n = 404) and a 12
      month period after (n = 263) incorporating the 24HW into routine practice.
      Overall supplementation rate, maximum weight loss, length of stay (LoS), and peak
      transcutaneous bilirubin (TcB) were compared. RESULTS: Overall supplementation
      rate decreased from 43.6% pre- to 27.4% postintervention and in first-time
      mothers from 51.9% to 31.0%. Among infants losing >=10% of BW, the
      supplementation rate decreased from 63.9% to 26.2%. There was no significant
      increase in maximum weight loss, peak TcB level, or LoS overall or in those with
      >=10% weight loss from birth. CONCLUSION: Routine use of 24HW as the reference
      for newborn weight loss calculation reduced supplementation and did not increase
      untoward effects during the hospital stay.

PMID- 29356563
TI  - Oxytocin Receptor Antagonist (Atosiban) in the Threat of Preterm Birth: Does It
      Have Any Effect on Breastfeeding in the Term Newborn?
AB  - AIM: Oxytocin is a hormone involved in the mechanism of breastfeeding, uterine
      contractions, and social relationships. Atosiban (competitive oxytocin
      antagonist) is one of the most commonly used tocolytics for the threat of preterm
      labor in Europe. The aim of this study is to determinate if the administration of
      atosiban has any influence in the type of feeding in the term newborn at
      discharge. The secondary objective is to verify its effectiveness for the
      prevention of preterm delivery and in the possibility of applying treatment to
      complete lung maturation. MATERIALS AND METHODS: Retrospective cohort study
      carried out in a tertiary University Hospital distinguished by WHO-UNICEF as a
      Baby-Friendly Hospital Initiative. The analysis included 264 women exposed to
      atosiban during a period of 4 years. One hundred met inclusion criteria.
      Unexposed infants born right after and before the exposed ones were selected as
      the not exposed subgroup (n = 200). RESULTS: Among women treated with atosiban,
      82% maintained exclusively breastfed (EBF), 8% had mixed breastfeeding, and 10%
      had formula feeding at discharge. In the nonexposed group, 82% maintained EBF,
      9.5% had mixed breastfeeding, and 8.5% had formula feeding at discharge (p =
      0.84). 97.5% of pregnant women treated with atosiban received corticosteroid for
      lung maturation, and 49.5% completed gestation with term newborns. CONCLUSION:
      There were no significant differences in the type of feeding at discharge between
      the atosiban group and the nonexposed group. In most cases, the administration of
      tocolytic therapy allowed to complete lung maturation.

PMID- 29356562
TI  - A radiofrequency device for tract ablation after liver biopsy: a single
      institution human feasibility study.
AB  - OBJECTIVE: The need for liver biopsy has been increasing because genetic testing
      of specimens has become important for determining prognosis and management in
      patients with hepatic malignancy. We evaluated the feasibility of a device for
      biopsy tract ablation in patients with hepatic masses. METHODS: This prospective
      single-center pilot study was approved by our institutional review board and
      patients provided written informed consent. Between September 2015 and March
      2016, 10 patients (6 males and 4 females, 35-66-years-old) who had hepatic masses
      and normal range of platelet count and prothrombin time were enrolled. After
      percutaneous ultrasound-guided biopsy, the biopsy tract was ablated with the
      device which consists of an insulation sheath and a radiofrequency applicator.
      Complications were evaluated with Doppler ultrasound immediately after the
      biopsy, with noncontrast abdominopelvic CT the day after the biopsy, and with a
      telephone interview 7 days after the biopsy. RESULTS: Tract ablation did not
      cause any pain in seven patients and caused minimal pain in three3 patients.
      Tract ablation was performed for a mean of 4.8 s (range, 4-6 s). No adverse
      events occurred during the procedure. Bleeding through the biopsy tract was not
      apparent on Doppler ultrasound, and abnormal fluid was not detected in the
      abdominal cavity on CT. Procedure-related complications were not reported on
      telephone interview. CONCLUSION: Biopsy tract ablation with the device is
      technically feasible. If the device is used appropriately considering its
      potential advantages, it may help to reduce the risk of complications associated
      with liver biopsy. Advances in knowledge: It is technically feasible to perform
      biopsy tract ablation with the radiofrequency ablation device after liver biopsy.

PMID- 29356564
TI  - Health professionals' perceptions of developing dementia services in primary care
      settings in China: a qualitative study.
AB  - OBJECTIVES: Primary care plays a crucial role in the timely diagnosis and proper
      management of dementia. Evidence from low and middle income countries is much
      needed to inform service development in primary care and to address the dementia
      burden in these countries. The aim of this study was to explore community health
      professionals' perceptions of dementia service development using China as a case.
      METHOD: An interpretive study design was utilized and focus groups were used for
      data collection guided by a semi-structured interview guide. Each focus group
      lasted between 90-120 min. Thematic analysis was applied for data analysis.
      RESULTS: Twenty-one community health professionals participated in this study and
      three major themes were identified. These themes are: incorporating dementia
      components in the government-subsidized primary care services; an under-prepared
      workforce to meet the demand for dementia care; and an enabling environment to
      sustain dementia care. CONCLUSION: Government policies, regulations, standards
      and guidelines need to be established for dementia service development in primary
      care to improve the home care for people with dementia and to create a dementia
      friendly society. Regular education and training activities for health
      professionals are a way to build dementia care service capacity in primary care.

PMID- 29356565
TI  - Intergenerational support, satisfaction with parent-child relationship and
      elderly parents' life satisfaction in Hong Kong.
AB  - OBJECTIVES: This study examines in what exchange patterns that three types of
      intergenerational support are associated with elderly parents' life satisfaction,
      and whether elderly parents' evaluation on parent-child relationship plays a
      mediation role on those associations. METHOD: Data were drawn from Hong Kong
      Panel Survey for Poverty Alleviation. Respondents aged 65 and over were included
      ( N=504). Three types of support, namely, daily-living, financial, and emotional
      support were examined in four patterns-the over-benefited , under-benefited ,
      reciprocal and no flow of exchange. A multivariable linear regression was applied
      to investigate the association between pattern of intergenerational exchange and
      life satisfaction, and mediation analysis was employed to examine the mediating
      role of satisfaction with parent-child relationship on their associations.
      RESULTS: Elderly parents were less satisfied with their lives when they had no
      flow of exchange in daily-living support, and more satisfied when they were under
      benefited in financial support, and over-benefited or reciprocal in emotional
      support. Elderly parents' satisfaction with parent-child relationship mediated
      the association between exchange of emotional support and life satisfaction; but
      not the association between daily-living or financial support and life
      satisfaction. CONCLUSION: Different types of intergenerational support are
      associated with elderly parents' life satisfaction in different patterns.

PMID- 29356567
TI  - The psychometric properties of the control, autonomy, self-realisation and
      pleasure scale (CASP-19) for older adults with dementia.
AB  - INTRODUCTION: Asset based approaches to dementia research and measurement
      emphasise the need to also assess the strengths and capabilities that people with
      dementia retain, rather than assessing only losses or deficits. The CASP-19
      proposes wellbeing as the satisfaction of four 'needs' (control, autonomy, self
      realisation and pleasure). The CASP-19 may reflect the asses-based approach and
      has been validated in over 20 countries. The aim of this study was to evaluate
      the CASP-19's psychometric properties in older adults with dementia. METHODS: An
      observational study was conducted at five NHS trusts across England. Participants
      were asked to either complete the CASP-19 by interview or self-report, alongside
      four other measures to assess psychometric properties. RESULTS: Internal
      consistency overall was good (alpha = .856) but the autonomy subscale fell below
      the acceptable. The CASP-19 was significantly correlated in the expected
      direction with measures of quality of life (r = .707), depression (r = -.707) and
      additional measures. It also remained moderately stable over a one-week period
      but factor analyses indicated a 12-item measure may be more robust. CONCLUSIONS:
      Despite some variations, the CASP-19 appears to have adequate psychometric
      properties for older adults with dementia and can be used in future research and
      practice.

PMID- 29356566
TI  - Pain intensity, depressive symptoms, and functional limitations among older
      adults with serious mental illness.
AB  - OBJECTIVE: To examine pain-related activity interference as a mediator for the
      relationship between pain intensity and depressive symptoms among older adults
      with serious mental illness (SMI). METHOD: Ordinary least-squares regressions
      were used to investigate the mediation analysis among older adults with SMI (n =
      183) from community mental health centers. Analyses used secondary data from the
      HOPES intervention study. RESULTS: Higher pain intensity was associated with
      greater pain-related activity interference. Higher pain intensity and pain
      related activity interference were also associated with elevated depressive
      symptoms. Finally, greater pain-related activity interference significantly
      mediated the association between higher pain intensity and elevated depressive
      symptoms. CONCLUSIONS: These findings demonstrate that pain and depressive
      symptoms may be linked to functional limitations. Clinicians and researchers in
      the mental health field should better address pain-related activity interference
      among older adults with SMI, especially among those with higher pain intensity
      and elevated depressive symptoms.

PMID- 29356568
TI  - Usability study and pilot validation of a computer-based emotion recognition test
      for older adults with Alzheimer's disease and amnestic mild cognitive impairment.
AB  - OBJECTIVES: This study aimed to carry out a pilot validation of Affect-GRADIOR, a
      computer-based emotion recognition test, with older adults. The study evaluated
      its usability, reliability and validity for the screening of people with
      Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). METHODS:
      The test was administered to 212 participants (76.37 +/- 6.20 years) classified
      into three groups (healthy controls, n = 69; AD, n = 84; and aMCI, n = 59) on the
      basis of detailed neurological, neuropsychological, laboratory and neuro-imaging
      evidence. Data on usability were collected by means of a questionnaire and
      automated evaluation. RESULTS: The validated test comprised 53 stimuli and 7
      practice items (one per emotion). Participants reported that Affect-GRADIOR was
      accessible and user-friendly. It had high internal consistency (ordinal
      Cronbach's alpha = 0.96). Test-retest reliability correlations were significant
      and robust (r = 0.840, p < 0.001). Exploratory factor analysis supported a seven
      factor model of the emotions assessed (neutral expression, happiness, surprise,
      disgust, sadness, anger and fear). Receiver operating characteristic curve
      analyses suggested that the test discriminated healthy older adults from AD and
      aMCI cases. Correct answer score improved MMSE predictive power from 0.547 to
      0.560 (Cox & Snell R2, p = 0.012), and Affect-GRADIOR speed of processing score
      improved MMSE predictive power from 0.547 to 0.563 (Cox & Snell R2, p = 0.010).
      CONCLUSIONS: Affect-GRADIOR is a valid instrument for the assessment of the
      facial recognition of emotions in older adults with and without cognitive
      impairment.

PMID- 29356570
TI  - How do community-dwelling LGBT people perceive sexuality in residential aged
      care? A systematic literature review.
AB  - OBJECTIVES: To investigate what empirical studies report on the perceptions of
      community-dwelling LGBT adults regarding sexuality and sexual expression in
      residential aged care (RAC), and how their sexuality should be addressed in RAC.
      METHODS: Relevant papers were identified through electronic searches in
      databases; and by reference tracking and citation tracking. Data were extracted
      using a standardized data extraction form and were compared, related, and
      synthesized using thematic analyses. We evaluated the methodological quality of
      the studies. RESULTS: Eighteen articles were identified. Three major topics
      emerged regarding sexuality in RAC: (1) factors affecting LGBT people's
      perceptions, subdivided into (a) discrimination, (b) loss of sexual identity, (c)
      failure to acknowledge the same-sex partner, and (d) lack of privacy; (2) LGBT
      specific RAC facilities; and (3) characteristics of LGBT friendly RAC facilities
      and caregivers. CONCLUSIONS: LGBT people have clear perceptions about how
      sexuality and sexual expression is or should be managed in RAC. Despite the
      general increase in acceptance of sexual minorities, many community-dwelling LGBT
      people believe older LGBT residents are discriminated against because of their
      sexual orientation or gender identity. Taking into account these opinions is
      crucial for increasing accessibility of RAC to LGBT people and to ensure the
      quality of the provided care.

PMID- 29356569
TI  - Olanzapine Versus Risperidone in Children and Adolescents with Psychosis: A Meta
      Analysis of Randomized Controlled Trials.
AB  - OBJECTIVE: To compare the efficacy and safety of olanzapine and risperidone in
      children and adolescents (aged <=18 years) with psychosis by conducting a meta
      analysis of randomized controlled trials (RCTs). METHODS: Several English and
      Chinese databases were searched for studies published before February 8th, 2017.
      Two independent investigators screened the studies according to prespecified
      criteria and extracted the data. Review Manager 5.3 was used to conduct the data
      synthesis. RESULTS: Eight RCTs involving 457 participants (225 participants in
      the olanzapine group and 232 participants in the risperidone group) were
      included. No significant differences were observed in the mean scores on the
      Positive and Negative Syndrome Scale/Brief Psychiatric Rating Scale (standard
      mean difference [SMD] = -0.06, 95% confidence intervals [CI] = [-0.31, 0.19], p =
      0.63), the positive symptom scores (SMD = -0.09, 95% CI = [-0.32, 0.15], p =
      0.48), or the negative symptom scores (SMD = -0.11 95% CI = [-0.34, 0.13], p =
      0.38) between the two groups. Regarding adverse effects, the mean increases in
      weight (MD = 2.90, 95% CI = [1.41, 4.39], p = 0.0001), body mass index (MD =
      0.90, 95% CI = [0.42, 1.38], p = 0.0003), and incidence of hypersomnia (risk
      ratios [RR] = 1.98, 95% CI = [1.15, 3.43], p = 0.01) were higher in the
      olanzapine group, while the incidence of insomnia (RR = 0.31, 95% CI = [0.11,
      0.85], p = 0.02), prolactin elevation (RR = 0.11, 95% CI = [0.01, 0.85], p =
      0.03), myotonia (RR = 0.12, 95% CI = [0.03, 0.49], p = 0.003), tremor (RR = 0.22,
      95% CI = [0.08, 0.63], p = 0.005), and akathisia (RR = 0.27, 95% CI = [0.12,
      0.57], p = 0.0007) was higher in the risperidone group. CONCLUSIONS: There is no
      significant difference in efficacy between olanzapine and risperidone for the
      treatment of children and adolescents with psychosis, but the side effect
      profiles of these two medications differ. High-quality RCTs are needed before
      recommending clinical treatment in children and adolescents.

PMID- 29356572
TI  - Unmet care needs, care provision and patient satisfaction in patients with a late
      life depression: a cross-sectional study.
AB  - BACKGROUND: Research has shown that some 30% of total care needs in people with
      late-life depression (LLD) are unmet. It is not known to what extent patients
      actually don't receive any care for these needs or consider the care to be
      insufficient and their satisfaction with the provided care. AIM: The aim of this
      study is to obtain insight into the care provided in relation to the reported
      unmet care needs and satisfaction with the total care provided is examined.
      METHOD: A cross-sectional study of 99 people with LLD in an ambulatory setting.
      RESULTS: In 67% of patients, at least one unmet need was ascertained. In most
      cases (80%) care was actually provided for those needs by professionals and/or
      informal caregivers. Patients were satisfied with the care delivered for 81% of
      the reported care needs. Satisfaction was lowest for social care needs (67%). For
      six specific care needs it was demonstrated that dissatisfied patients were
      significantly more depressed than satisfied patients. CONCLUSION: Even though
      patients might receive care for certain needs, this does not mean that their
      needs are met. A substantial proportion of patients with LDD feel that they need
      additional help for unmet needs.

PMID- 29356571
TI  - A Biomimetic Emu Oil-Blended Electrospun Nanofibrous Mat for Maintaining Stemness
      of Adipose Tissue-Derived Stem Cells.
AB  - BACKGROUND: Emu oil (EO) with anti-inflammatory, antioxidative, and wound healing
      properties can be blended for preparing bioactive nanofibrous scaffold. Adipose
      tissue-derived stem cells (ADSCs) are promising candidates for tissue
      engineering, and preserving their stemness potential is vital for further
      therapeutic applications. AIM: The aim of this study was to fabricate EO-blended
      nanofiber and investigate its effect on proliferation, survival, and stemness
      preservation of ADSCs. MATERIALS AND METHODS: Pure EO composition was
      characterized using a gas chromatograph mass spectrometer. EO-PCL-polyethylene
      glycol (PEG) nanofibers were successfully fabricated using an electrospinning
      technique and characterized by field emission scanning electron microscopy (FE
      SEM) and fourier-transform infrared spectroscopy (FTIR). Cell viability and
      adhesion were measured using the MTT assay and FE-SEM. Finally, quantitative PCR
      (qPCR) was used to quantify the expression level of cell cycle regulated genes
      and pluripotency-associated transcription factors. RESULTS: Findings showed that
      20% (w/w) of EO is the optimum oil content in the electrospun solution to achieve
      good morphology and ultrafine fibers. The relatively high optical densities and
      FE-SEM images indicated that EO highly supported cell adhesion and proliferation
      on the matrices. In addition, EO-PCL-PEG electrospun nanofibrous mats
      significantly upregulated the expression levels of cell cycle regulated genes
      (Cyclin D1, pRb, and P53) and stemness markers (Nanog, OCT-4, Rex-1, and Sox-2)
      than PCL-PEG nanofiber and tissue culture polystyrene in 7 and 14 days of cell
      culture. CONCLUSION: These results demonstrate that the EO-blended nanofibrous
      mat can be used as a bioactive scaffold to support cell adhesion and
      proliferation while simultaneously maintaining the stemness of ADSCs.

PMID- 29356573
TI  - Spur-of-the-Moment Modification in National Treatment Policies Leads to a
      Surprising HCV Viral Suppression in All Treated Patients: Real-Life Egyptian
      Experience.
AB  - The aim of this study was to retrospectively analyze the outcome of an
      unscheduled change in national Egyptian policies for the treatment of hepatitis C
      virus (HCV), which was transpired as a result of a reduction in interferon
      supplies, and to manage patients who already started interferon-based therapy.
      After completing a priming 4-weeks course of sofosbuvir/pegylated
      interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of
      sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the
      sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of
      patients; Group 1, which included patients who had the previous regimen with IFN
      priming, and group 2, which included the first consecutive group of patients who
      received SOF/DCV for 12 weeks from the start without IFN priming. All group 1
      patients (1,214 patients) achieved SVR12 (100%) and this was statistically
      significant when compared with the overall SVR12 in group 2 [8,869 patients with
      sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse
      events were reported in both groups. In this real-life treatment experience,
      interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a
      priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV
      viral suppression in all treated patients.

PMID- 29356574
TI  - Pyruvate Kinase M2 Modulates the Glycolysis of Chondrocyte and Extracellular
      Matrix in Osteoarthritis.
AB  - Pyruvate kinase M2 (PKM2) has been wildly verified to modulate glycolysis in
      tumor cells. However, the role of PKM2 on the glycolysis of osteoarthritis (OA)
      chondrocytes is still unclear. In present study, we investigate the function of
      PKM2 on OA chondrocyte glycolysis and the collagen matrix generation in vitro.
      Results showed that PKM2 was upregulated in OA chondrocytes compared with healthy
      control chondrocytes. In OA chondrocytes, ATP expression was lower compared with
      healthy control chondrocytes. Loss-of-function experiment showed that PKM2
      knockdown mediated by lentivirus transfection could significantly suppress the
      glucose consumption and lactate secretion levels and decrease glucose transporter
      1 (Glut-1), lactate dehydrogenase A (LDHA), and hypoxia inducible factor 1-alpha
      (HIF-1alpha), indicating the inhibition of PKM2 knockdown on glycolysis.
      Moreover, Cell Counting Kit-8 (CCK-8), flow cytometry, and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay showed
      that PKM2 knockdown inhibited OA chondrocyte proliferation and promoted the
      apoptosis. Western blot and immunocytochemical staining showed that PKM2
      knockdown downregulated the expression levels of COL2A1 and SOX-9. In summary,
      our results conclude that PKM2 modulates the glycolysis and extracellular matrix
      generation, providing the vital role of PKM2 on OA pathogenesis and a novel
      therapeutic target for OA.

PMID- 29356575
TI  - Anxiety Partially Mediates Cybersickness Symptoms in Immersive Virtual Reality
      Environments.
AB  - The use of virtual reality (VR) in psychological treatment is expected to
      increase. Cybersickness (CS) is a negative side effect of VR exposure and is
      associated with treatment dropout. This study aimed to investigate the following:
      (a) if gender differences in CS can be replicated, (b) if differences in anxiety
      and CS symptoms between patients and controls can be replicated, and (c) whether
      the relationship between exposure to VR and CS symptoms is mediated by anxiety. A
      sample (N = 170) of participants with different levels of psychosis liability was
      exposed to VR environments. CS and anxiety were assessed with self-report
      measures before and after the VR experiment. This study replicated gender
      differences in CS symptoms, most of which were present before exposure to VR. It
      also replicated findings that a significant correlation between anxiety and CS
      can be found in healthy individuals, but not in patients. In a VR environment,
      anxiety partially mediated CS symptoms, specifically nausea and disorientation. A
      partial explanation for the differences found between patients and controls may
      lie in a ceiling effect for the symptoms of CS. A second explanation may be the
      partial overlap between CS symptoms and physiological anxiety responses. CS
      symptoms reported at baseline cannot be explained by exposure to VR, but are
      related to anxiety. Caution is required when interpreting studies on both CS and
      anxiety, until the specificity in measurements has been improved. Since anxiety
      mediated the CS symptoms, CS is expected to decline during treatment together
      with the reduction of anxiety.

PMID- 29356577
TI  - History of the Treatment of Female Sexual Dysfunction(s).
AB  - This article reviews the history of the treatment of women's sexual problems from
      the Victorian era to the twenty-first century. The contextual nature of
      determining what constitutes female sexual psychopathology is highlighted.
      Conceptions of normal sexuality are subject to cultural vagaries, making it
      difficult to identify female sexual dysfunctions. A survey of the inclusion,
      removal, and collapsing of women's sexual diagnoses in the Diagnostic and
      Statistical Manual of Mental Disorders from 1952 to 2013 illuminates the biases
      in the various editions. Masters and Johnson's models of sexual response and
      dysfunction paved the way for the diagnosis and treatment of women's sexual
      dysfunctions. Their sex therapy paradigm is described. Conceptions of and
      treatments for anorgasmia, arousal difficulties, vaginismus, dyspareunia, and low
      desire are reviewed. The medicalization of human sexuality and the splintering of
      sex therapy are discussed, along with current trends and new directions in sexual
      health care for women.

PMID- 29356576
TI  - Effect of Alpha-Lipoic Acid on Clinical and Neurophysiologic Recovery of Carpal
      Tunnel Syndrome: A Double-Blind, Randomized Clinical Trial.
AB  - The objective of our study was to examine the effect of alpha-lipoic acid (ALA)
      on clinical and neurophysiologic outcomes after surgery for idiopathic carpal
      tunnel syndrome (CTS). We conducted a randomized, double-blind, placebo
      controlled clinical trial in 20 adults diagnosed with idiopathic CTS after
      clinical and neurophysiologic assessment. Eligible participants took 600 mg ALA
      or placebo per day for 1 month before surgery, and for 2 months afterward.
      Further clinical and neurophysiologic assessments were undertaken immediately
      before surgical decompression, and at 12 weeks postoperatively with additional
      clinical assessments at the 4th and 8th week after surgery. Clinical outcome
      measures were taken by Boston Questionnaire score, the presence or absence of
      Tinel's sign, and Phalen's test findings. Median nerve conduction studies were
      also undertaken and interpreted according to Dumitru's reference values. Nineteen
      patients completed the study; one member of the placebo group was lost during
      follow-up. There were significant improvements in clinical and neurophysiologic
      variables in the ALA treatment group, present even before surgery. Boston
      Questionnaire scores had improved significantly in both groups. In the ALA group,
      none of the participants had positive Phalen's or Tinel's signs at 12 weeks, and
      motor and sensory fiber latency and amplitude had significantly improved; in the
      placebo group, only the sensory distal latency had improved significantly. In
      conclusion, ALA administered 1 month before open decompression and for 2 months
      afterward improves the clinical and neurophysiologic outcomes after surgery.

PMID- 29356578
TI  - No Evidence for the Pathogenicity of the BRCA2 c.6937 + 594T>G Deep Intronic
      Variant: A Case-Control Analysis.
AB  - BACKGROUND: The role of deep intronic variants in hereditary cancer
      susceptibility has been largely understudied. Previously, the BRCA2 c.6937 +
      594T>G variant has been shown to preferentially promote the inclusion of a 95
      nucleotide cryptic exon and to introduce a premature termination codon. Our
      objective was to further assess the pathogenicity of the BRCA2 c.6937 + 594T>G
      deep intronic variant. PATIENTS AND METHODS: We examined the association between
      BRCA2 c.6937 + 594T>G and breast cancer (BC) risk in 464 BC cases and 497
      noncancer controls from Puerto Rico. RESULTS: The overall frequency of the G
      allele was 2.1% in this population. There was no association between the TG/GG
      genotypes and BC risk in the uncorrected model and after correcting for
      confounders. There was only one carrier of the GG genotype. This individual did
      not have personal or family history of cancer and did not meet the National
      Comprehensive Cancer Network criteria for hereditary cancer genetic testing.
      CONCLUSIONS: Although previous work has demonstrated that the BRCA2 c.6937 +
      594T>G variant affects splicing, this association study does not support a
      pathogenic role for the BRCA2 c.6937 + 594T>G intronic variant in breast and
      ovarian cancer syndrome susceptibility. Furthermore, it emphasizes the need to
      take into account multiple diverse populations in association studies for the
      assessment of variant pathogenicity.

PMID- 29356579
TI  - Insulin Treatment Cannot Promote Lipogenesis in Rat Fetal Lung in Gestational
      Diabetes Mellitus Because of Failure to Redress the Imbalance Among SREBP-1,
      SCAP, and INSIG-1.
AB  - Gestational diabetes mellitus (GDM) has a higher incidence of neonatal
      respiratory distress syndrome, and lipogenesis is required for the synthesis of
      pulmonary surfactants. The aim of this study was to determine the effect of
      insulin treatment in GDM on the production of lipids in the lungs of fetal rats.
      GDM was induced by streptozotocin, and insulin was used to manage diabetes. Type
      II alveolar epithelial cells (AEC II), bronchoalveolar lavage fluid (BALF), and
      lung tissues of the neonatal rats were sampled for analyses. Insulin treatment
      could not decrease plasma glucose to normal level at a later gestational stage.
      Lipids/phospholipids in AEC II, BALF, and lung tissues decreased in GDM, and
      insulin treatment could not increase the levels; quantitative PCR and western
      blotting demonstrated a lower level of sterol regulator element-binding protein 1
      (SREBP-1), SREBP cleavage-activating protein (SCAP), and insulin-induced gene 1
      (INSIG-1) in GDM, but insulin treatment upregulated only SREBP-1. Nuclear
      translocation of the SREBP-1 protein in AEC II was impaired in GDM, which could
      not be ameliorated by insulin treatment. These findings indicated that insulin
      treatment in GDM cannot promote lipogenesis in the fetal lung because of failure
      to redress the imbalance among SREBP-1, SCAP, and INSIG-1.

PMID- 29356580
TI  - Natural Products from Single Plants as Sleep Aids: A Systematic Review.
AB  - Insufficient sleep, insomnia, and sleep-related problems are important health
      issues, as their overall prevalence accounts for about 30% of the general
      population. The aim of this study was to systematically review previous studies
      investigating the effects of orally administered single plant-derived extracts on
      sleep-related outcomes in humans. Data sources were PubMed, Google Scholar, and
      Cochrane Library. The data search was conducted in two steps: step 1, names of
      plants which have been studied as sleep aids in humans were searched and
      retrieved; and step 2, each ingredient listed in step 1 was then added into the
      search term. Only original articles or reviews were applicable to the scope of
      this review. Studies on human subjects, with or without sleep-related disorders,
      were included. Sleep-related disorders refer to not only insomnia or sleep
      behavior disorders but also diseases with sleep-related symptoms. Studies were
      considered eligible for this review when the plant extracts were administered
      orally. Outcome measures relevant to sleep quality, duration, or other sleep
      related problems were included. Twenty-one plants were listed in the first step
      of the search as potential candidates for natural sleep aids. Seventy-nine
      articles using these single plant-derived natural products were included in the
      final review. Although valerian was most frequently studied, conflicting results
      were reported, possibly due to the various outcome measures of each study. Other
      plants were not as rigorously tested in human studies. There was limited evidence
      with inconclusive results regarding the effects of single plant-derived natural
      products on sleep, warranting further studies.

PMID- 29356581
TI  - Acanthosis Palmaris: A Rare Paraneoplastic Manifestation of Non-Small-Cell Lung
      Cancer.

PMID- 29356582
TI  - Treating Tretinoin Ostealgia With Pamidronate.

PMID- 29356583
TI  - Comparison of Antiobesity Effects Between Gochujangs Produced Using Different
      Koji Products and Tabasco Hot Sauce in Rats Fed a High-Fat Diet.
AB  - In this study, we compared the antiobesity effects between gochujangs prepared
      using different koji products and Tabasco hot sauce in rats fed a high-fat diet
      (HFD). Male Sprague-Dawley rats were fed HFD containing four different types of
      10% gochujang powder or 0.25% commercial Tabasco sauce powder for 8 weeks. The
      body weight gain, liver and epididymal and mesenteric fat pad weights, serum
      leptin levels, and lipogenesis-related mRNA levels of HFD-gochujang
      supplementation groups were significantly decreased compared with those of the
      HFD group. In addition, gochujang supplement significantly reduced adipocyte
      size; hepatic triglyceride and total cholesterol levels; the occurrence of fatty
      liver deposits and steatosis by inhibiting lipogenesis through downregulation of
      fatty acid synthase, acetly-CoA carboxylase, and glucose-6-phosphate
      dehydrogenase. These effects were greater in the gochujang-supplemented groups
      than the Tabasco hot sauce-supplemented group. The gochujang prepared by
      nutritious giant embryo rice koji and soybean koji was most effective in terms of
      antiobesity effects, compared with the other tested gochujangs. In gochujangs,
      the antiobesity effects are mediated by high levels of secondary metabolites such
      as isoflavone, soyasaponin, capsaicin, and lysophosphatidylcholine. The current
      results indicated that the gochujang products have the potential to reduce fat
      accumulation and obesity.

PMID- 29356584
TI  - Self-Reactive B Cells in the Germinal Center Reaction.
AB  - Maintenance of immunological self-tolerance requires lymphocytes carrying self
      reactive antigen receptors to be selectively prevented from mounting destructive
      or inflammatory effector responses. Classically, self-tolerance is viewed in
      terms of the removal, editing, or silencing of B and T cells that have formed
      self-reactive antigen receptors during their early development. However, B cells
      activated by foreign antigen can enter germinal centers (GCs), where they further
      modify their antigen receptor by somatic hypermutation (SHM) of their
      immunoglobulin genes. The inevitable emergence of activated, self-reactive GC B
      cells presents a unique challenge to the maintenance of self-tolerance that must
      be rapidly countered to avoid autoantibody production. Here we discuss current
      knowledge of the mechanisms that enforce B cell self-tolerance, with particular
      focus on the control of self-reactive GC B cells. We also consider how self
      reactive GC B cells can escape self-tolerance to initiate autoantibody production
      or instead be redeemed via SHM and used in productive antibody responses.

PMID- 29356585
TI  - Correlation Between Single-Nucleotide Polymorphisms Within miR-30a and Related
      Target Genes and Risk or Prognosis of Nephrotic Syndrome.
AB  - This study was aimed to figure out the association of single-nucleotide
      polymorphisms (SNPs) within miR-30a and its downstream molecules (i.e., Notch1,
      Snail1, p53, CD73, and TET1) with susceptibility to and prognosis of nephrotic
      syndrome (NS). In the aggregate, 265 patients and 281 healthy controls were
      gathered, and related laboratory indicators were examined. The miR-30a, Notch1,
      Snail1, TET1, p53, and CD73 expressions were also evaluated by quantitative real
      time polymerase chain reaction (qRT-PCR), immunohistochemistry, or enzyme-linked
      immunosorbent assay. Besides, the SNPs were genotyped by RT-PCR with aid of ABI
      PRISMTM 377 DNA sequencing instrument. As a result, the NS patients were
      correlated with remarkably higher 24-h protein excretion, random urine
      protein/creatinine (UPCR), and serum creatinine, along with lower estimated
      glomerular filtration rate and serum albumin, when compared with normal subjects
      (p < 0.05). Furthermore, significant correlations were present between miR-30a
      expression and the expressions of Notch1 (rs = -0.350), p53 (rs = -0.339), CD73
      (rs = -0.300), TET1 (rs = -0.249), and Snail1 (rs = -0.829) (all p < 0.05). The
      SNPs of miR-30a [i.e., rs2222722 (C>T)], Notch1 [i.e., rs3124599 (G>A), rs3124591
      (C>T), and rs139994842 (G>A)], Snail1 [i.e., rs6020178 (T>C)], p53 [i.e.,
      rs1042522 (C>G)], and CD73 [i.e., rs9444348 (G>A) and rs4431401 (T>C)] were
      significantly correlated with both differed NS risk and altered hormone
      sensitivity to NS (all p < 0.05). Moreover, haplotype AC of CD73 and haplotype
      ATG of Notch1 were the helpful factors against NS (p < 0.05), yet haplotype GT of
      CD73 functioned oppositely (p < 0.05). The haplotype AT of CD73 was beneficial to
      the NS patients for that the carriers could be treated with hormones without
      severe complications (p < 0.05). Conclusively, the SNPs situated within miR-30a
      and its downstream molecules (i.e., Notch1, Snail1, p53, CD73, and TET1) could
      become the promising biomarkers for both NS diagnosis and prediction of NS
      prognosis.

PMID- 29356586
TI  - Fate of Paralytic Shellfish Toxins in Southern Rock Lobster ( Jasus edwardsii)
      during Cooking: Concentration, Composition, and Distribution.
AB  - Paralytic shellfish toxin (PST) producing microalgal blooms have a significant
      economic impact on the Southern Rock Lobster ( Jasus edwardsii) fishery in
      Tasmania, Australia. The regulatory level of 0.8 mg of saxitoxin (STX) eq/kg in
      place for bivalve shellfish fisheries is applied to lobster hepatopancreas during
      blooms of toxic algae, resulting in harvest closures and ongoing risk management
      implications for the fishery. This cooking study was undertaken to inform a human
      health risk assessment, in conjunction with studies on the uptake and elimination
      of PST in J. edwardsii. Live lobsters in tanks were contaminated through
      consumption of PST-containing mussels harvested during an Alexandrium tamarense
      Group 1 bloom event. This resulted in a mean lobster hepatopancreas level of 2.83
      +/- 0.84 mg of STX.2HCl eq/kg. Other edible tissues contained negligible
      concentrations of toxin. PST concentrations in all tissues did not significantly
      change after boiling or steaming, although the amount of hepatopancreas available
      for consumption did decrease significantly with both cooking methods, because the
      tissue became more dispersed, resulting in an overall reduction in the toxin
      exposure per hepatopancreas consumed. The toxin profile was dominated by STX;
      gonyautoxin 2, 3; N-sulfocarbamoyl-gonyautoxin 2, 3 (C1,2); and gonyautoxin 5. No
      significant changes to the toxin profile were observed after either of the
      cooking methods. Pate, bisque, and souffle prepared from the hepatopancreas of
      toxic lobsters contained negligible levels of PST in each serving; on average, a
      serving of pate contained 0.01 mg of STX.2HCl eq, whereas a serving of bisque or
      souffle contained <0.01 mg of STX.2HCl eq. The findings of this study will inform
      a risk assessment of PST in J. edwardsii to determine risk management options for
      this fishery in Australia.

PMID- 29356587
TI  - Biochemical, Oxidative, and Physiological Changes Caused by Acute Exposure of
      Fentanyl and Its 3 Analogs in Rodents.
AB  - Synthesis and bioefficacy of fentanyl and its 8 new 1-substituted analogs (1-8)
      were earlier reported by us. Of these 8 compounds, N-(1-(2-phenoxyethyl)-4
      piperidinyl)propionanilide (2), N-isopropyl-3-(4-( N-phenylpropionamido)piperidin
      1-yl)propanamide (5), and N- t-butyl-3-(4-( N-phenylpropionamido)piperidin-1-yl)
      propanamide (6) were found to be more effective and less toxic compared to
      fentanyl. The present study reports the acute effect of fentanyl (0.50 Median
      Lethal Dose (LD50); intraperitoneal) and its 3 analogs (2, 5, and 6) on various
      biochemical and oxidative parameters in mice and various physiological parameters
      in rats. Blood alkaline phosphatase (1 hour and 7 days) and urea levels (1 hour)
      were significantly elevated by fentanyl, while alanine aminotransferase levels (1
      hour) were increased by both fentanyl and analog 2 compared to the corresponding
      control. Increase in partial pressure of carbon dioxide and decrease in partial
      pressure of oxygen were also caused by fentanyl and analog 2 (1 hour). Analog 6
      alone elevated malondialdehyde levels in the brain, liver, and kidney tissues (7
      days). The LD50 of fentanyl and analogs 2, 5, and 6 were found to be 0.879,
      87.88, 69.80, and 55.44 mg/kg, respectively, in rats. Significant decrease in
      heart rate, mean arterial pressure, respiratory rate (RR), and neuromuscular
      transmission was produced by fentanyl and analog 2, while analog 5 decreased the
      RR alone. The changes, particularly the respiratory depression, were found to be
      reversed by naloxone, a MU-receptor antagonist. Thereby, indicating involvement
      of MU-receptor mediated effects of the compounds. To conclude, all the analogs
      were found to be less toxic compared to fentanyl, suggesting their possible role
      in pain management.

PMID- 29356588
TI  - Experiences of Care of Adolescents and Young Adults with Cancer in Australia.
AB  - PURPOSE: To examine the care experiences of Australian Adolescents and Young
      Adults (AYAs) with cancer during a period when youth cancer services (YCS) were
      developing across the country. METHODS: A cross-sectional, self-report survey
      completed by 207 recently diagnosed AYAs with cancer, recruited from the
      population-based cancer registries of Australia's two most populous states. AYAs
      were 15 to 24 years old when diagnosed with any form of cancer (except melanoma
      <3 mm or stage I/II). Respondents indicated whether certain events/experiences
      occurred at various points along the cancer care pathway and the treatment
      centers attended. Treatment centers with YCS were identified. RESULTS:
      Participating AYAs were an average of 9 months post-diagnosis. AYAs were treated
      in over 60 centers, with only 31% attending YCS. While experiences relating to
      delivery of treatment were generally positive, supportive care experiences and
      emotional support were missing for many. Information provision at the end of
      treatment was low, with 60% not receiving a treatment summary and 50% not
      receiving a written follow-up care plan. In addition, 42% never/rarely received
      information relevant to their age, and only 54% reported that healthcare
      professionals definitely checked their understanding of the information provided.
      AYAs attending YCS were more likely to report age-appropriate treatment settings,
      information provision, and emotional support. CONCLUSION: While care experiences
      were generally positive for most AYAs, attending YCS was associated with better
      communication and supportive care experiences. As only a third of the AYAs
      surveyed attended these services, efforts are needed to increase AYA access to
      YCS.

PMID- 29356589
TI  - Polytetrafluoroethylene-Covered Stent Graft Versus Bare Stent in Transjugular
      Intrahepatic Portosystemic Shunt: Systematic Review and Meta-Analysis.
AB  - BACKGROUND & AIMS: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is used
      to control refractory variceal bleeding secondary to portal hypertension. This
      meta-analysis was conducted to systematically review polytetrafluoroethylene
      covered stent grafts (CS) versus bare stents (BS) in TIPS procedure. METHODS:
      Systematic search of literature databases was done from January-1990 till April
      2017, using predecided keywords. Outcome measures studied were (1) primary
      patency (PP) at 1 year (defined as absence of shunt insufficiency at 1 year), (2)
      rebleeding (RE) (3) new-onset hepatic encephalopathy ([HE] new-onset or worsening
      encephalopathy following the procedure), and (4) survival at 1 year (SU). Odds
      ratio (OR) was calculated for each outcome variable. Between-study heterogeneity
      was assessed by the I2 statistics and chi2 Q-test. RESULTS: Fourteen studies (4
      RCTs, 2 prospective nonrandomized, and 8 retrospective) were included with 2519
      patients (1548 patients in BS group and 971 patients in CS group). Three-quarter
      outcome measures showed significantly better results with CS. PP was pooled from
      13 studies and showed an OR = 4.75 (95% confidence interval [CI] = 3.32-6.79; P <
      .00001; I2 = 44%) in favor of CS. RE was pooled from six studies with odds ratio
      (OR) = 0.37(95% CI = 0.24-0.56; P < .00001; I2 = 0%) in favor of CS. SU was
      pooled from 11 studies with OR = 1.85 (95% CI = 1.44-2.38; P < .00001; I2 = 0%)
      in favor of CS. On subset analysis for RCTs, three outcome variables favored CS
      with minimal heterogeneity [PP: OR = 4.18 (95% CI = 2.66-6.55; P < .00001; I2 =
      0%). RE: OR = 0.43 (95% CI = 0.25-0.72; P < .001; I2 = 0%). SU: OR = 1.85 (95% CI
      = 1.44-2.38, P < .00001; I2 = 0%)]. HE showed no difference between two stents on
      the overall and subset pooled analysis. Overall: OR = 0.86 (95% CI = 0.68-1.08; P
      = .19; I2 = 4%). Only RCTs: OR = 0.91 (95% CI = 0.63-1.32, P = .63; I2 = 0%).
      CONCLUSIONS: CS is associated with better primary patency and survival and lesser
      rate of rebleeding than BS in patients undergoing TIPS procedure. There is no
      difference in new-onset hepatic encephalopathy.

PMID- 29356591
TI  - Gender-Specific Differences in Access to Polysomnography and Prevalence of Sleep
      Disorders.
AB  - BACKGROUND: Previous studies have shown that women have less access or longer
      waiting times to high-tech medicine compared with men. This study aimed to detect
      possible gender differences in access to the diagnostic high-tech method of
      polysomnography (PSG). Furthermore, the study explored gender differences in
      prevalence of specific sleep diseases. MATERIALS AND METHODS: Source data of n =
      1000 patients, who underwent PSG at the Medical University of Innsbruck, were
      reviewed. Clinical data regarding time elapsed between symptom onset and PSG as
      well as final diagnoses were analyzed for gender differences. RESULTS: Six
      hundred sixty-nine men and 331 women were examined with PSG. There were no gender
      differences in access to PSG after first presentation to the sleep laboratory.
      Significantly more men than women (13.3 vs. 6.9%) were referred to medical
      examination because of abnormal observations by their bed partner. In men we
      found more sleep-related breathing disorders and fragmentary myoclonus, whereas
      in women insomnia was more common. Sleep-related breathing disorders showed a
      more severe manifestation in men, however, there was no difference in treatment
      with continuous positive airway pressure/biphasic positive airway pressure
      therapy between male and female patients. CONCLUSION: Twice as many men than
      women received a PSG. This is explained by the referral rates to the sleep
      laboratory. While there are well-established gender differences for some sleep
      disorders, the fact that twice as many men than women were referred to the sleep
      laboratory could indicate a lower awareness for sleep disorders in women.

PMID- 29356590
TI  - Taking Psychedelics Seriously.
AB  - BACKGROUND: Psychiatric research in the 1950s and 1960s showed potential for
      psychedelic medications to markedly alleviate depression and suffering associated
      with terminal illness. More recent published studies have demonstrated the safety
      and efficacy of psilocybin, MDMA, and ketamine when administered in a medically
      supervised and monitored approach. A single or brief series of sessions often
      results in substantial and sustained improvement among people with treatment
      resistant depression and anxiety, including those with serious medical
      conditions. Need and Clinical Considerations: Palliative care clinicians
      occasionally encounter patients with emotional, existential, or spiritual
      suffering, which persists despite optimal existing treatments. Such suffering may
      rob people of a sense that life is worth living. Data from Oregon show that most
      terminally people who obtain prescriptions to intentionally end their lives are
      motivated by non-physical suffering. This paper overviews the history of this
      class of drugs and their therapeutic potential. Clinical cautions, adverse
      reactions, and important steps related to safe administration of psychedelics are
      presented, emphasizing careful patient screening, preparation, setting and
      supervision. CONCLUSION: Even with an expanding evidence base confirming safety
      and benefits, political, regulatory, and industry issues impose challenges to the
      legitimate use of psychedelics. The federal expanded access program and right-to
      try laws in multiple states provide precendents for giving terminally ill
      patients access to medications that have not yet earned FDA approval. Given the
      prevalence of persistent suffering and growing acceptance of physician-hastened
      death as a medical response, it is time to revisit the legitimate therapeutic use
      of psychedelics.

PMID- 29356592
TI  - Complex Decongestive Therapy Enhances Upper Limb Functions in Patients with
      Breast Cancer-Related Lymphedema.
AB  - BACKGROUND: We aimed to evaluate the effects of complex decongestive therapy
      (CDT) on upper extremity functions, the severity of pain, and quality of life. We
      also searched the impact of the sociodemographic and clinical characteristics on
      the improvement in upper extremity functions. METHODS: A total of 37 women with
      breast cancer-related lymphedema (BCRL) [age, 53.6 +/- 11.2 (28-72)] were
      included in this study. All patients underwent CDT-phase 1 program, including
      meticulous skin care, manual lymphatic drainage, remedial exercises, and
      compression bandages. Arm volume was calculated by a formula for truncated cone
      using circumferential measurements. A baseline questionnaire, including
      sociodemographic and clinical properties, was used for each patient. Short Form
      36 (SF-36), Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, and
      Visual Analog Scale (VAS) for pain and heaviness were used as clinical assessment
      scales. RESULTS: The mean of the posttreatment volume of the affected limb was
      lower compared to pretreatment volume (2741.81 +/- 696.85 and 2990.67 +/- 745.49,
      respectively), and the mean percentage change in edema volume was 38.1% +/-
      26.5%. We observed a statistically significant reduction in pain and heaviness
      VAS scores and improvement of shoulder mobility among upper extremities with
      lymphedema (p < 0.001) after CDT. The mean of posttreatment DASH score was lower
      compared to pretreatment score (37.19 +/- 16.01, 49.81 +/- 18.84, respectively, p
      < 0.001). All subgroups of the SF-36 parameters were increased after the CDT
      application (p < 0.01). Besides being under 65 years old, having a body mass
      index above 30 and short duration of lymphedema were found to be related to
      greater improvement in upper extremity functions. CONCLUSIONS: CDT provides
      enhancement of upper extremity functions and quality of life in patients with
      BCRL. The reduction in lymphedema volume, pain, and heaviness and the improvement
      in shoulder mobility may be the contributed factors.

PMID- 29356593
TI  - A Blend of Extracts from Houttuynia cordata, Nelumbo nucifera, and Camellia
      sinensis Protects Against Ethanol-Induced Liver Damage in C57BL/6 Mice.
AB  - The protective activity of a mixture of aqueous and ethanolic extracts from
      Houttuynia cordata Thunb, Nelumbo nucifera G. leaves, and Camellia sinensis seed
      (HNC) was evaluated in C57BL/6 mice. Pretreatment with HNC prevented the
      elevation of serum aspartate aminotransferase and alanine aminotransferase caused
      by ethanol-induced hepatic damage. The HNC-treated mice showed significantly
      lower triglyceride levels, reduced CYP2E1 activity, and increased antioxidant
      enzyme activities and lipogenic mRNA levels. These results suggest that HNC might
      be a candidate agent for liver protection against ethanol-induced oxidative
      damage, through enhancement of antioxidant and antilipogenic activity.

PMID- 29356594
TI  - Proteomic Analysis of Alterations in Aeromonas hydrophila Outer Membrane Proteins
      in Response to Oxytetracycline Stress.
AB  - In Gram-negative bacteria, the outer membrane proteins (OMPs) perform a crucial
      role in antibiotic resistance, but it is largely unknown how they behave in
      response to antibiotic stress. In this study, we treated Aeromonas hydrophila
      with two different doses of oxytetracycline (OXY) to induce antibiotic stress.
      Proteins were isolated from sarcosine-insoluble fractions and quantitatively
      examined by using tandem mass tag labeling-based mass spectrometry to identify
      differentially expressed proteins. As a result, we identified 125 differential
      proteins in the 5 MUg/ml OXY treatment group, including 20 OMPs, and 150 proteins
      from the 10 MUg/ml OXY group, including 22 OMPs. Gene ontology analysis showed
      that translation-related proteins, including 30S and 50S ribosome proteins, were
      significantly enriched in increasing abundance under OXY stress; whereas the
      downregulated proteins were associated with the transport process, such as
      maltodextrin, maltose, and oligosaccharide transport. We then validated a subset
      of the identified differential proteins by using Western blot and quantitative
      polymerase chain reaction analyses. Finally, the quantitative real-time PCR
      (qPCR) results showed that at the transcription level, the expression of five OMP
      genes, including AHA_1280 (protein name A0KHS0), AHA_1281 (A0KHS1), AHA_1447
      (A0KI84, BamE), AHA_1861 (A0KJE1), and AHA_2766 (A0KLX3), and one lipoprotein
      gene AHA_1740 (A0KJ25) was consistent with proteomic results under 5 and 10
      MUg/ml OXY treatment, respectively. In addition, the Western blotting also
      demonstrated that two altered OMP proteins A0KHS1 and A0KHH2 were upregulated for
      both OXY treatment groups. This study indicates that bacteria regulate the
      expression levels of OMPs in response to antibiotic stress and further contribute
      to our understanding of the functions of OMPs in antibiotic resistance. Moreover,
      our results suggest that the upregulation of translation and downregulation of
      the transport process may affect bacterial fitness during OXY stress. These
      findings may provide new clues to the antibiotic resistance mechanism in A.
      hydrophila.

PMID- 29356595
TI  - Correlation Between Changes in Extremity Volume and Bioelectrical Impedance in
      Arm and Leg Lymphedema.
AB  - BACKGROUND: To clarify the differences in the mode of fluid accumulation between
      arm and leg lymphedema using bioelectrical impedance analysis (BIA). METHODS AND
      RESULTS: In 22 arms with lymphedema (ALE) and 65 legs with lymphedema (LLE), as
      well as 54 legs with venous edema (VE) for comparison, BIA was performed twice
      between April 2015 and March 2017. Then, the changes in BIA-derived parameters
      were correlated with the changes in extremity volumes. In ALE, the change in
      extracellular fluid resistance (Re) was negatively correlated with the change in
      arm volume (r = 0.51), while the change in intracellular fluid resistance (Ri)
      was constant, irrespective of the change in arm volume (r = 0.19). In LLE, the
      change in Re was negatively correlated with the change in leg volume (r = 0.67),
      but the change in Ri was also negatively correlated with the change in leg volume
      (r = 0.51). These correlations were similar to those in VE, in which the changes
      in Re and Ri were each negatively correlated with the change in leg volume (r =
      0.66 and 0.53, respectively). CONCLUSION: The modes of change in BIA-derived
      parameters according to the change in extremity volume were different in ALE and
      LLE. The changes in LLE were similar to that in VE.

PMID- 29356596
TI  - Effect of Lymphaticovenous Anastomosis in Breast Cancer-Related Lymphedema: A
      Review of the Literature.
AB  - BACKGROUND: Lymphedema affects ~15% of all patients after breast cancer
      treatment. The aim of this review was to assess the clinical effects (improvement
      in arm circumference and quality of life) of lymphaticovenous anastomosis (LVA)
      in treating breast cancer-related lymphedema (BCRL). METHODS AND RESULTS: A
      systematic literature search was conducted in Medline, Embase and the Cochrane
      Library in July 2017, to identify all studies on LVA for the treatment of BCRL.
      The primary outcome was limb volume or circumference reduction and the secondary
      outcome was the improvement of quality of life. The search yielded 686 results,
      of which 15 articles were included in this review. All studies reported on BCRL
      in terms of volume or circumference reduction. Thirteen out of the included
      studies reported a positive surgical effect on reduction in volume or
      circumference. Twelve articles mentioned qualitative measures, being symptom
      improvement and improvement in quality of life. The number of patients who
      experienced symptoms relief ranged from 50% to 100% in the studies. CONCLUSIONS:
      The current review showed that the effects of LVA for the treatment of BCRL are
      variable among studies, although overall LVA seems effective in early stage BCRL.
      Higher quality studies are needed to confirm the effectiveness of LVA.

PMID- 29356597
TI  - Rapid and Specific Methods to Differentiate Foodborne Pathogens, Campylobacter
      jejuni, Campylobacter coli, and the New Species Causing Spotty Liver Disease in
      Chickens, Campylobacter hepaticus.
AB  - Campylobacter jejuni and Campylobacter coli play a major role in bacteria-related
      foodborne illness in humans. Recently, a newly identified species, Campylobacter
      hepaticus, was shown to be the causative agent of spotty liver disease in
      chickens. The pathogenic potential of C. hepaticus in humans is unknown. This new
      species contains genes usually used to detect C. jejuni and C. coli in DNA-based
      detection methods, such as the hippuricase (hipO) gene and the glyA (serine
      hydroxymethyltransferase) gene, with a high degree of similarity. Therefore,
      polymerase chain reaction (PCR) primers used to detect these species need to be
      evaluated carefully to prevent misidentification of these important Campylobacter
      species. A multiplex PCR was developed and optimized to simultaneously and
      specifically identify the presence of C. jejuni, C. coli, and C. hepaticus in
      chicken samples containing high-complexity microbiota. The assay represents a new
      diagnostic tool for investigating the epidemiology of Campylobacter colonization
      in poultry and environmental samples. It may also be applicable to the
      investigation of Campylobacter contamination in food and in outbreaks of
      campylobacteriosis.

PMID- 29356598
TI  - Diagnostic Accuracy of Exercise Electrocardiogram in Women.

PMID- 29356600
TI  - Correction to: Cryoprotectant Toxicity: Facts, Issues, and Questions, by Best BP.
      Rejuvenation Res 2015;18(5):422-436; DOI: 10.1089/rej.2014.1656.

PMID- 29356599
TI  - Early Goal-Directed Therapy: The History and Ongoing Impact on Management of
      Severe Sepsis and Septic Shock.
AB  - The use of early goal-directed therapy (EGDT) for the management of severe sepsis
      and septic shock, a practice put forth by Dr. Rivers et al. in 2001, ushered in a
      new era of targeted sepsis therapy. After its publication, several further
      studies helped validate the protocolized approach to sepsis management,
      ultimately leading to its incorporation into the Surviving Sepsis Campaign
      guidelines. Since that time, however, a trio of large multi-center randomized
      controlled trials have taken place to evaluate the efficacy of EGDT when compared
      with usual care and have demonstrated that strict adherence to the entirety of
      the original EGDT protocol is unnecessary for improved outcomes. Some
      recommendations, such as higher goal hemoglobin and hematocrit levels and liberal
      crystalloid fluid resuscitation, are likely harmful. Despite controversy over a
      number of the recommendations, early identification of sepsis, source control,
      and prompt empiric antibiotic administration remain the mainstay of treatment for
      patients with sepsis and septic shock.

PMID- 29356601
TI  - The gap between behavioral risk status and willingness to change behavior among
      healthcare professionals.
AB  - AIMS:: This study explored behavioral health risk factors among healthcare
      professionals and investigated the at-risk persons' satisfaction with their
      health habits and ongoing change attempts. METHODS:: The study was based on a
      cross-sectional web-based survey directed at the nurses and physicians ( N =
      1233) in Finnish healthcare. Obesity, low physical activity, smoking, and risky
      alcohol drinking were used as behavioral health risk factors. RESULTS:: In all,
      70% of the participants had at least one behavioral risk factor, and a
      significant number of at-risk persons were satisfied with their health habits and
      had no ongoing change process. Good self-rated health and good self-rated work
      ability were significantly associated with whether a participant had a behavioral
      health risk factor. CONCLUSION:: Overall, unhealthy behaviors and a lack of
      ongoing change attempts were commonly observed among healthcare professionals.
      Work in healthcare is demanding, and healthy lifestyles can support coping. Thus,
      healthy lifestyle programs should also be targeted to healthcare professionals.

PMID- 29356602
TI  - Effect of Diabetes Sleep Education for T2DM Who Sleep After Midnight: A Pilot
      Study from China.
AB  - BACKGROUND: Our prior study showed that patients with sleep disorders had poor
      blood pressure (BP), glycemic control, and more severe complications. Therefore,
      sleep is very important for diabetic control. Our work was to investigate whether
      individualized diabetes sleep education significantly improve sleep quality and
      glycemic control in type 2 diabetic patients who sleep after midnight and
      potential mechanism by a randomized parallel interventional study. METHODS: T2D
      patients were randomly recruited to an intervention or control group. Patients
      received structured special diabetes sleep education program with 3-month follow
      up. Pittsburg Sleep Quality Index (PSQI) was scored for each participant.
      Demographic data, HbA1c, biochemical, and some hormones were also examined. SPSS
      13.0 was used for statistical analysis. RESULTS: One hundred patients were
      approached, and 45 were enrolled into our trial. Eventually, 31 patients
      completed the study. Patients in the intervention group greatly improved their
      sleep hygiene. After intervention, PSQI scores were lowered significantly (-1.48
      +/- 0.88 vs. -0.51 +/- 0.71, P < 0.001), as well as significant reduction of
      HbA1c (-1.5 +/- 0.55 vs. -1.11 +/- 0.47, P < 0.05). Fasting plasma glucose was
      also lowered significantly. Homeostasis model assessment of insulin resistance
      was reduced significantly (-1.29 +/- 0.97 vs. 1.04 +/- 0.91, P < 0.01). Serum
      concentrations for interleukin (IL)-6, cortisol, and ghrelin were decreased
      significantly. Ghrelin (coefficients -0.65, P < 0.001), cortisol (coefficients 
      0.38, P < 0.05), and IL-6 (coefficients 0.452, P < 0.05) were correlated with
      HbA1c improvement. The change of ghrelin was negatively associated with the
      improvement of HbA1c. CONCLUSION: Diabetes sleep education could improve sleep
      quality, better blood glucose and BP, and decrease insulin resistance through
      healthier sleep hygiene. Lower serum concentration of ghrelin might be partly
      involved in the reduction of HbA1c.

PMID- 29356603
TI  - Effects of the Preoperative Administration of Dexketoprofen Trometamol on Pain
      and Swelling After Implant Surgery: A Randomized, Double-Blind Controlled Trial.
AB  - The fear of postoperative pain is often mentioned by patients as one of the
      factors that is most frequently associated with dental implants. To reduce this
      factor, a single oral dose of 25 mg dexketoprofen trometamol (DKT) or placebo was
      administered 15 minutes before implant surgery. One hundred patients who required
      single-implant treatments were randomly assigned to 1 of 2 blinded groups. The
      patients in the test group were given 25 mg DKT (DKT group), and those in the
      control group were given 500 mg vitamin C as a placebo (PLACEBO group). A
      subjective visual analogue scale of 100 mm in length was used to evaluate pain.
      Inflammation and complications were assessed using a 5-point Likert scale. An
      analysis of variance, t-tests, and a Mann-Whitney U test were performed. Among
      the 100 patients, 83 completed the study (there were 8 dropouts in the PLACEBO
      group and 9 in the DKT group). The patients who received DKT reported a lower
      pain intensity during the immediate postoperative period. The inflammatory
      response was weaker in the DKT group than the control group at 48 hours, but
      bleeding was greater. There were no other complications in either of the groups.
      In conclusion, the preemptive use of 25 mg soluble DKT administered orally 15
      minutes before implant surgery can reduce the severity of immediate postoperative
      pain.

PMID- 29356605
TI  - Overstating the Effects of Loving-Kindness Meditation: Comment on Kok et al.
      (2013).

PMID- 29356604
TI  - Procalcitonin: Usefulness in Acute Care Surgery and Trauma.
AB  - BACKGROUND: Procalcitonin (PCT) is a serum biomarker currently suggested by the
      Surviving Sepsis Campaign to aid in determination of the appropriate duration of
      therapy in sepsis patients. We review the use of procalcitonin in patients after
      trauma or acute care surgery. METHOD: A MEDLINE search via PubMed was performed
      using the combination of "procalcitonin" and "humans" and "injuries, trauma,"
      "wounds and injuries," or "wounds." Studies of burn patients, children, other
      biomarkers, and non-acute care surgery were excluded. RESULTS: Procalcitonin may
      be useful in identifying infection in trauma and post-operative acute care
      surgery. However, heterogenity exists among patients, and surgery and trauma
      alone elevate PCT even in the absence of infection. CONCLUSIONS: Although trends
      in PCT concentrations may offer insight, no standard approach can be recommended
      currently.

PMID- 29356606
TI  - Predictors of Specialized Pediatric Palliative Care Involvement and Impact on
      Patterns of End-of-Life Care in Children With Cancer.
AB  - Purpose The impact of specialized pediatric palliative care (SPPC) teams on
      patterns of end-of-life care is unknown. We sought to determine (1) which
      children with cancer access SPPC and (2) the impact of accessing SPPC on the risk
      of experiencing high-intensity end-of-life care (intensive care unit admission,
      mechanical ventilation, or in-hospital death). Methods Using a provincial
      childhood cancer registry, we assembled a retrospective cohort of Ontario
      children with cancer who died between 2000 and 2012 and received care through
      pediatric institutions with an SPPC team. Patients were linked to population
      based administrative data capturing inpatient, outpatient, and emergency visits.
      Children were classified as having SPPC, general palliative care, or no
      palliative care on the basis of SPPC clinical databases, physician billing codes,
      or inpatient diagnosis codes. Results Of the 572 children, 166 (29%) received
      care from an SPPC team for at least 30 days before death, and 100 (17.5%)
      received general palliative care. SPPC involvement was significantly less likely
      for children with hematologic cancers (OR, 0.3; 95% CI, 0.3 to 0.4), living in
      the lowest income areas (OR, 0.4; 95% CI, 0.2 to 0.8), and living further from
      the treatment center (OR, 0.5; 95% CI, 0.4 to 0.5). SPPC was associated with a
      five-fold decrease in odds of intensive care unit admission (OR, 0.2; 95% CI, 0.1
      to 0.4), whereas general palliative care had no impact. Similar associations were
      seen with all secondary indicators. Conclusion When available, SPPC, but not
      general palliative care, is associated with lower intensity care at the end of
      life for children with cancer. However, access remains uneven. These results
      provide the strongest evidence to date supporting the creation of SPPC teams.

PMID- 29356607
TI  - Effects of Aerobic and Resistance Exercise on Metabolic Syndrome, Sarcopenic
      Obesity, and Circulating Biomarkers in Overweight or Obese Survivors of Breast
      Cancer: A Randomized Controlled Trial.
AB  - Purpose Metabolic syndrome is associated with an increased risk of cardiovascular
      disease, type 2 diabetes, and breast cancer recurrence in survivors of breast
      cancer. This randomized controlled trial assessed the effects of a 16-week
      combined aerobic and resistance exercise intervention on metabolic syndrome,
      sarcopenic obesity, and serum biomarkers among ethnically diverse, sedentary,
      overweight, or obese survivors of breast cancer. Methods Eligible survivors of
      breast cancer (N = 100) were randomly assigned to exercise (n = 50) or usual care
      (n = 50). The exercise group participated in supervised moderate-to-vigorous-65%
      to 85% of heart rate maximum-aerobic and resistance exercise three times per week
      for 16 weeks. Metabolic syndrome z-score (primary outcome), sarcopenic obesity,
      and serum biomarkers were measured at baseline, postintervention (4 months), and
      3-month follow-up (exercise only). Results Participants were age 53 +/- 10.4
      years, 46% were obese, and 74% were ethnic minorities. Adherence to the
      intervention was 95%, and postintervention assessments were available in 91% of
      participants. Postintervention metabolic syndrome z-score was significantly
      improved in exercise versus usual care (between-group difference, -4.4; 95% CI, 
      5.9 to -2.7; P < .001). Sarcopenic obesity (appendicular skeletal mass index, P =
      .001; body mass index, P = .001) and circulating biomarkers, including insulin (
      P = .002), IGF-1 ( P = .001), leptin ( P = .001), and adiponectin ( P = .001),
      were significantly improved postintervention compared with usual care. At 3-month
      follow-up, all metabolic syndrome variables remained significantly improved
      compared with baseline in the exercise group ( P < .01). Conclusion Combined
      resistance and aerobic exercise effectively attenuated metabolic syndrome,
      sarcopenic obesity, and relevant biomarkers in an ethnically diverse sample of
      sedentary, overweight, or obese survivors of breast cancer. Our findings suggest
      a targeted exercise prescription for improving metabolic syndrome in survivors of
      breast cancer and support the incorporation of supervised clinical exercise
      programs into breast cancer treatment and survivorship care plans.

PMID- 29356608
TI  - Continued Excellent Outcomes in Previously Untreated Patients With Follicular
      Lymphoma After Treatment With CHOP Plus Rituximab or CHOP Plus 131I-Tositumomab:
      Long-Term Follow-Up of Phase III Randomized Study SWOG-S0016.
AB  - Purpose SWOG S0016 was a phase III randomized study that compared the safety and
      efficacy of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine,
      and prednisone) with CHOP-RIT (CHOP followed by consolidation with iodine-133
      tositumomab radioimmunotherapy) for previously untreated patients with follicular
      lymphoma. Understanding the long-term outcome of patients provides a benchmark
      for novel treatment regimens for FL. Patients and Methods Between 2001 and 2008,
      531 previously untreated patients with FL were randomly assigned to receive
      either six cycles of R-CHOP or six cycles of CHOP-RIT. Patients with advanced
      stage disease (bulky stage II, III, or IV) of any pathologic grade (1, 2, or 3)
      were eligible. Results After a median follow-up of 10.3 years, 10-year estimates
      of progression-free and overall survival were 49% and 78% among all patients,
      respectively. Patients in the CHOP-RIT arm had significantly better 10-year
      progression-free survival compared with patients in the R-CHOP arm (56% v 42%; P
      = .01), but 10-year overall survival was not different between the two arms (75%
      v 81%; P = .13). There was no significant difference between the CHOP-RIT and R
      CHOP arms in regard to incidence of second malignancies (15.1% v 16.1%; P = .81)
      or myelodysplastic syndrome or acute myeloid leukemia (4.9% v 1.8%; P = .058).
      The estimated 10-year cumulative incidences of death resulting from second
      malignancies were not different (7.1% v 3.2%; P = .16), but cumulative incidence
      of death resulting from myelodysplastic syndrome or acute myeloid leukemia was
      higher in the CHOP-RIT arm compared with the R-CHOP arm (4% v 0.9%; P = .02).
      Conclusion Given these outstanding outcomes, immunochemotherapy should remain the
      standard induction approach for patients with high-risk FL until long-term follow
      up of alternative approaches demonstrates superiority.

PMID- 29356610
TI  - Restoring Body Image After Cancer (ReBIC): Results of a Randomized Controlled
      Trial.
AB  - Purpose This study aimed to test a group psychosocial intervention focused on
      improving disturbances of body image (BI), sexual functioning, and quality of
      life in breast cancer (BC) survivors. Methods A prospective, randomized
      controlled trial was conducted to assess the efficacy of an 8-week group
      intervention in women after BC treatment. The manual-based intervention combined
      two powerful ingredients: expressive guided-imagery exercises integrated within a
      model of group-therapy principles. The intervention facilitates exploration of
      identity, the development of new self-schemas, and personal growth. In addition,
      the intervention included an educational component on the social and cultural
      factors affecting women's self-esteem and BI. The control condition included
      standard care plus educational reading materials. One hundred ninety-four BC
      survivors who had expressed concerns about negative BI and/or difficulties with
      sexual functioning participated in the study; 131 were randomly assigned to the
      intervention, and 63 were assigned to the control condition. Participants were
      followed for 1 year. Results Women in the intervention group reported
      significantly less concern/distress about body appearance ( P < .01), decreased
      body stigma ( P < .01), and lower level of BC-related concerns ( P < .01),
      compared with women in the control group. BC-related quality of life was also
      better in the intervention group compared with the control group at the 1-year
      follow-up ( P < .01). There was no statistically significant group difference in
      sexual functioning. Conclusion Restoring Body Image After Cancer (ReBIC), a group
      intervention using guided imagery within a group-therapy approach, is an
      effective method for addressing BI-related concerns and quality of life post-BC.
      The manual-based intervention can be easily adapted to both cancer centers and
      primary care settings.

PMID- 29356609
TI  - Epidemiologic Evidence That Excess Body Weight Increases Risk of Cervical Cancer
      by Decreased Detection of Precancer.
AB  - Purpose Obesity has been inconsistently linked to increased cervical cancer
      incidence and mortality; however, the effect of obesity on cervical screening has
      not been explored. We investigated the hypothesis that increased body mass might
      decrease detection of cervical precancer and increase risk of cervical cancer
      even in women undergoing state-of-the-art screening. Methods We conducted a
      retrospective cohort study of 944,227 women age 30 to 64 years who underwent
      cytology and human papillomavirus DNA testing (ie, cotesting) at Kaiser
      Permanente Northern California (January 2003 to December 2015). Body mass index
      was categorized as normal/underweight (< 25 kg/m2), overweight (25 to < 30
      kg/m2), or obese (>= 30 kg/m2). We estimated 5-year cumulative risks of cervical
      precancer and cancer by category of body mass index using logistic Weibull
      survival models. Results We observed lower risk of cervical precancer (n = 4,489)
      and higher risk of cervical cancer (n = 490) with increasing body mass index.
      Specifically, obese women had the lowest 5-year risk of precancer (0.51%; 95% CI,
      0.48% to 0.54% v 0.73%; 95% CI, 0.70% to 0.76% in normal/underweight women; P
      trend < .001). In contrast, obese women had the highest 5-year risk of cancer
      (0.083%; 95% CI, 0.072% to 0.096% v 0.056%; 95% CI, 0.048% to 0.066% in
      normal/underweight women; P trend < .001). Results were consistent in subgroups
      defined by age (30 to 49 v 50 to 64 years), human papillomavirus status (positive
      v negative), and histologic subtype (glandular v squamous). Approximately 20% of
      cervical cancers could be attributed to overweight or obesity in the women in our
      study who underwent routine cervical screening. Conclusion In this large,
      screened population, overweight and obese women had an increased risk of cervical
      cancer, likely because of underdiagnosis of cervical precancer. Improvements in
      equipment and/or technique to assure adequate sampling and visualization of women
      with elevated body mass might reduce cervical cancer incidence.

PMID- 29356611
TI  - A Universal Noninvasive Continuous Blood Pressure Measurement System for Remote
      Healthcare Monitoring.
AB  - BACKGROUND: The effectiveness of any remote healthcare monitoring system depends
      on how much accurate, patient-friendly, versatile, and cost-effective measurement
      it is delivering. There has always been a huge demand for such a long-term
      noninvasive remote blood pressure (BP) measurement system, which could be used
      worldwide in the remote healthcare industry. Thus, noninvasive continuous BP
      measurement and remote monitoring have become an emerging area in the remote
      healthcare industry. INTRODUCTION: Photoplethysmography-based (PPG) BP
      measurement is a continuous, unobtrusive, patient-friendly, and cost-effective
      solution. However, BP measurements through PPG sensors are not much reliable and
      accurate due to some major limitations like pressure disturbance, motion
      artifacts, and variations in human skin tone. MATERIALS AND METHODS: A novel
      reflective PPG sensor has been developed to eliminate the abovementioned pressure
      disturbance and motion artifacts during the BP measurement. Considering the
      variations of the human skin tone across demography, a novel algorithm has been
      developed to make the BP measurement accurate and reliable. The training dataset
      captured 186 subjects' data and the trial dataset captured another new 102
      subjects' data. RESULTS AND DISCUSSION: The overall accuracy achieved by using
      the proposed method is nearly 98%. Thus, demonstrating the efficacy of the
      proposed method. CONCLUSIONS: The developed BP monitoring system is quite
      accurate, reliable, cost-effective, handy, and user friendly. It is also expected
      that this system would be quite useful to monitor the BP of infants, elderly
      people, patients having wounds, burn injury, or in the intensive care unit
      environment.

PMID- 29356612
TI  - Gaps in Psychiatric Training Could Challenge Delivery of Optimal Schizophrenia
      Pharmacotherapy.

PMID- 29356615
TI  - From the Editor-in-Chief's Desk.

PMID- 29356614
TI  - Current Advances in the Use of Therapeutic Hypothermia.

PMID- 29356616
TI  - Teledermatology in the United States: An Update in a Dynamic Era.
AB  - BACKGROUND: Teledermatology is rapidly advancing in the United States. The last
      comprehensive survey of U.S. teledermatology programs was conducted in 2011.
      INTRODUCTION: This article provides an update regarding the state of
      teledermatology programs in the United States. MATERIALS AND METHODS: Active
      programs were identified and surveyed from November 2014 to January 2017.
      Findings regarding practice settings, consult volumes, payment methods, and
      delivery modalities were compared to those from the 2011 survey. Findings from
      the Veterans Affairs (VA) were reported as an aggregate. RESULTS: There were 40
      active nongovernmental programs, amounting to a 48% increase and 30%
      discontinuation rate over five years. Academia remained the most common practice
      setting (50%). Median annual consultation volume was comparable with 263
      consultations, but maximum annual consultation volume increased (range: 20
      20,000). The most frequent payment method was self-pay (53%). Store-and-forward
      continued to be the most common delivery modality. In Fiscal Year 2016, the VA
      System consisted of 62 consultation sites and performed a total of 101,507
      consultations. DISCUSSION: The limitations of this study were that consult volume
      and payment methods were not available from all programs. CONCLUSION: U.S.
      teledermatology programs have increased in number and annual consultation volume.
      Academia is the most prevalent practice setting, and self-pay is the dominant
      accepted payment method. Innovative platforms and the provision of direct-to
      patient care are changing the practice of teledermatology.

PMID- 29356617
TI  - Using Zebrafish to Bring Hands-On Laboratory Experiences to Urban Classrooms.
AB  - Zebrafish are widely used as a model organism for research. Zebrafish embryos are
      also a useful resource for teaching students about vertebrate development. Here
      we describe a collaboration between two high school teachers and two university
      professors that used zebrafish to bring hands-on laboratory experiences to inner
      city students, with the aim of increasing tangibility, and improving student
      understanding and retention, of several fundamental scientific concepts, such as
      the scientific method, cell division, mitosis, and Mendelian genetics. We
      describe and provide supporting material for each of the four laboratory modules
      that we developed. We also discuss the obstacles that we encountered and include
      suggestions of ways to overcome these. This collaboration provides an example of
      how high school teachers with very little zebrafish experience can gain the
      knowledge and confidence to develop and implement modules such as these in a
      relatively short period of time. Owing to the wide availability of zebrafish
      resources, these laboratories should provide a useful resource for other teachers
      who are interested in integrating more hands-on, inquiry-based investigations
      using live animals into their classes. We also hope to encourage other zebrafish
      researchers to collaborate with local teachers in similar projects.

PMID- 29356619
TI  - The Effect of Nasoalveolar Molding on Nasal Airway Anatomy: A 9-Year Follow-up of
      Patients With Unilateral Cleft Lip and Palate.
AB  - OBJECTIVE: To determine the effects of nasoalveolar molding (NAM) on nasal airway
      architecture. DESIGN: Retrospective case-control study of patients with
      unilateral cleft lip treated with NAM vs without NAM. SETTING: Tertiary referral
      center specializing in cleft and craniofacial care. Patients, Participants, and
      Interventions: Thirty-six patients with complete unilateral cleft lip and
      alveolus: 19 with NAM therapy and 17 without NAM therapy. MAIN OUTCOME MEASURES:
      Cone beam computed tomography (CBCT) scans were compared in multiple coronal
      sections and were evaluated for linear and angular septal deviation, inferior
      turbinate hypertrophy, and linear and 2-dimensional airway area. RESULTS: There
      were no significant differences in linear or angular septal deviation, inferior
      turbinate area, linear stenosis, or airway area between NAM- and non-NAM-treated
      patients. CONCLUSIONS: NAM effectively molds the external nasal cartilage and
      structures but may have limited effects on internal nasal structures.

PMID- 29356618
TI  - Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic
      Drift.
AB  - Influenza A virus (IAV) imposes a significant socioeconomic burden on humanity.
      Vaccination is effective in only 60% of individuals, even under optimal
      circumstances. The difficulty stems from the remarkable ability of IAV to evade
      existing immunity. IAV's error prone polymerase enables the rapid antigenic
      evolution of the two virion surface glycoproteins, neuraminidase and
      hemagglutinin (HA). Since the most potent antibodies (Abs) at neutralizing viral
      infectivity are directed the head of the HA, amino acid substitutions in this
      region enable IAV to evade Ab-based immunity. Here, we review recent progress in
      understanding how immunodominance, the tendency of the immune system to respond
      to foreign immunogens in a hierarchical manner, shapes IAV evolution.

PMID- 29356620
TI  - Variations in Velopharyngeal Structure in Adults With Repaired Cleft Palate.
AB  - OBJECTIVE: The purpose of this study was to examine differences in velopharyngeal
      structures between adults with repaired cleft palate and normal resonance and
      adults without cleft palate. DESIGN: Thirty-six English-speaking adults,
      including 6 adults (2 males and 4 females) with repaired cleft palate (M = 32.5
      years of age, SD = 17.4 years) and 30 adults (15 males and 15 females) without
      cleft palate (M = 23.3 years of age, SD = 4.1 years), participated in the study.
      Fourteen velopharyngeal measures were obtained on magnetic resonance images and
      compared between groups (cleft and noncleft). RESULTS: After adjusting for body
      size and sex effects, there was a statistically significant difference between
      groups for 10 out of the 14 velopharyngeal measures. Compared to those without
      cleft palate, participants with repaired cleft palate had a significantly shorter
      hard palate height and length, shorter levator muscle length, shorter intravelar
      segment, more acute levator angles of origin, shorter and thinner velum, and
      greater pharyngeal depth. CONCLUSION: Although significant differences were
      evident in the cleft palate group, individuals displayed normal resonance. These
      findings suggest that a wide variability in velopharyngeal anatomy can occur in
      the presence of normal resonance, particularly for those with repaired cleft
      palate. Future research is needed to understand how anatomic variability impacts
      function, such as during speech.

PMID- 29356621
TI  - Behavioral-Social Adjustment of Adolescents with Craniofacial Microsomia.
AB  - OBJECTIVE: The objective was to assess differences in psychosocial adjustment
      between adolescents with and without craniofacial microsomia (CFM). DESIGN: This
      is a case-control follow-up study in adolescents with and without CFM. SETTING:
      Participants were originally recruited as infants from 26 cities across the
      United States and Canada. PARTICIPANTS: Participants included 142 adolescents
      with CFM (cases) and 316 peers without CFM (controls), their caregivers, and
      their teachers. MAIN OUTCOME MEASURES: Social and behavior measures from the
      Achenbach System of Empirically Based Assessments (ASEBA), the PedsQL: Core
      Version, and the Children's Communication Checklist-2nd edition (CCC-2) were
      used. Linear regression was used to estimate case-control differences and
      corresponding standardized effect sizes (ES) and 95% confidence intervals after
      adjustment for sociodemographic confounds. We also examined case-control
      differences by facial phenotype and hearing status. RESULTS: The magnitude and
      direction of case-control differences varied across assessment and respondent,
      but were generally modest (ES = -0.4 to 0.02, P values ranged from .003 to .85).
      There was little evidence for variation in case-control differences across
      different facial phenotypes or as a function of hearing status. CONCLUSIONS: Our
      results suggest that in spite of multiple risk factors, adolescents with CFM
      exhibit behavior problems no more frequently than their peers without CFM. Future
      studies of individuals with CFM should focus on resilience and social coping
      mechanisms, in addition to maladjustment.

PMID- 29356623
TI  - Effect of History of Mild Traumatic Brain Injury on Optic Nerve Sheath Diameter
      Changes after Valsalva Maneuver.
AB  - Optic nerve sheath diameter (ONSD) measured by transocular ultrasound is a marker
      of real-time intracranial pressure (ICP). The objective of this study was to
      evaluate the association between optic nerve sheath (ONS) dilation after a
      Valsalva maneuver and a prior history of mild to moderate traumatic brain injury
      (mTBI) in a heterogeneous sample of participants. Participants were excluded if
      they had had a recent brain injury, were symptomatic from a prior brain injury,
      had a history consistent with severe TBI and/or had undergone intracranial
      surgery. Ninety-five participants with and without a history of mTBI were
      included in the study. Transocular ultrasound of the ONS was performed before and
      after a Valsalva maneuver. Differences in the ONSD before and after a Valsalva
      maneuver were analyzed and correlated to the participants' history of mTBI.
      Baseline ONSD measurements between groups were not statistically significant.
      Following Valsalva, participants with a history of mTBI had a statistically
      significant increase in the ONSD compared with participants with no history of
      mTBI. This significant difference persisted after controlling for age, race, and
      sex. This study demonstrated an association between a prior history of mTBI and
      dilation of the ONS after Valsalva maneuver in a sample of asymptomatic
      participants, which was not seen in participants without a history of mTBI.

PMID- 29356622
TI  - Evidence-Based Review of Clinical Diagnostic Tests and Predictive Clinical Tests
      That Evaluate Response to Conservative Rehabilitation for Posterior Glenohumeral
      Instability: A Systematic Review.
AB  - CONTEXT: Posterior glenohumeral instability is poorly understood and can be
      challenging to recognize and evaluate. Using evidence-based clinical and
      predictive tests can assist clinicians in appropriate assessment and management.
      OBJECTIVE: To review evidence-based clinical diagnostic tests for posterior
      glenohumeral instability and predictive tests that identify responders to
      conservative management. DATA SOURCES: A comprehensive electronic bibliographic
      search was conducted using Embase, Ovid MEDLINE, PEDro, and CINAHL databases from
      their date of inception to February 2017. STUDY SELECTION: Studies were included
      for further review if they (1) reported on clinical diagnostic tests for
      posterior or posteroinferior instability of the glenohumeral joint, (2) assessed
      predictive clinical tests for posterior instability of the glenohumeral joint,
      and (3) were in English. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE:
      Level 4. DATA EXTRACTION: Data were extracted from the studies by 2 independent
      reviewers and included patient demographics and characteristics, index/reference
      test details (name and description of test), findings, and data available to
      calculate psychometric properties. RESULTS: Five diagnostic and 2 predictive
      studies were selected for review. There was weak evidence for the use of the jerk
      test, Kim test, posterior impingement sign, and O'Brien test as stand-alone
      clinical tests for identifying posterior instability. Additionally, there was
      weak evidence to support the use of the painless jerk test and the hand squeeze
      sign as predictive tests for responders to conservative management. These
      findings are attributed to study design limitations, including small and/or
      nonrepresentative samples. CONCLUSION: Clustering of thorough history and
      physical examination findings, including the aforementioned tests, may identify
      those with posterior glenohumeral instability and assist in developing management
      strategies.

PMID- 29356625
TI  - Multi-Omics for Biomarker Discovery and Target Validation in Biofluids for
      Amyotrophic Lateral Sclerosis Diagnosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a rare but usually fatal neurodegenerative
      disease characterized by motor neuron degeneration in the brain and the spinal
      cord. Two forms are recognized, the familial that accounts for 5-10% and the
      sporadic that accounts for the rest. New studies suggest that ALS is a highly
      heterogeneous disease, and this diversity is a major reason for the lack of
      successful therapeutic treatments. Indeed, only two drugs (riluzole and
      edaravone) have been approved that provide a limited improvement in the quality
      of life. Presently, the diagnosis of ALS is based on clinical examination and lag
      period from the onset of symptoms to the final diagnosis is ~12 months.
      Therefore, the discovery of robust molecular biomarkers that can assist in the
      diagnosis is of major importance. DNA sequencing to identify pathogenic gene
      variants can be applied in the cases of familial ALS. However, it is not a
      routinely used diagnostic procedure and most importantly, it cannot be applied in
      the diagnosis of sporadic ALS. In this expert review, the current approaches in
      identification of new ALS biomarkers are discussed. The advent of various multi
      omics biotechnology platforms, including miRNomics, proteomics, metabolomics,
      metallomics, volatolomics, and viromics, has assisted in the identification of
      new biomarkers. The biofluids are the most preferable material for the analysis
      of potential biomarkers (such as proteins and cell-free miRNAs), since they are
      easily obtained. In the near future, the biofluid-based biomarkers will be
      indispensable to classify different ALS subtypes and understand the molecular
      heterogeneity of the disease.

PMID- 29356626
TI  - Not Everyone Fits the Mold: Intratumor and Intertumor Heterogeneity and
      Innovative Cancer Drug Design and Development.
AB  - Disruptive innovations in medicine are game-changing in nature and bring about
      radical shifts in the way we understand human diseases, their treatment, and/or
      prevention. Yet, disruptive innovations in cancer drug design and development are
      still limited. Therapies that cure all cancer patients are in short supply or do
      not exist at all. Chief among the causes of this predicament is drug resistance,
      a mechanism that is much more dynamic than previously understood. Drug resistance
      has limited the initial success experienced with biomarker-guided targeted
      therapies as well. A major contributor to drug resistance is intratumor
      heterogeneity. For example, within solid tumors, there are distinct subclones of
      cancer cells, presenting profound complexity to cancer treatment. Well-known
      contributors to intratumor heterogeneity are genomic instability, the
      microenvironment, cellular genotype, cell plasticity, and stochastic processes.
      This expert review explains that for oncology drug design and development to be
      more innovative, we need to take into account intratumor heterogeneity. Initially
      thought to be the preserve of cancer cells, recent evidence points to the highly
      heterogeneous nature and diverse locations of stromal cells, such as cancer
      associated fibroblasts (CAFs) and cancer-associated macrophages (CAMs). Distinct
      subpopulations of CAFs and CAMs are now known to be located immediately adjacent
      and distant from cancer cells, with different subpopulations exerting different
      effects on cancer cells. Disruptive innovation and precision medicine in clinical
      oncology do not have to be a distant reality, but can potentially be achieved by
      targeting these spatially separated and exclusive cancer cell subclones and CAF
      subtypes. Finally, we emphasize that disruptive innovations in drug discovery and
      development will likely come from drugs whose effect is not necessarily tumor
      shrinkage.

PMID- 29356624
TI  - From Genomics to Omics Landscapes of Parkinson's Disease: Revealing the Molecular
      Mechanisms.
AB  - Molecular mechanisms of Parkinson's disease (PD) have already been investigated
      in various different omics landscapes. We reviewed the literature about different
      omics approaches between November 2005 and November 2017 to depict the main
      pathological pathways for PD development. In total, 107 articles exploring
      different layers of omics data associated with PD were retrieved. The studies
      were grouped into 13 omics layers: genomics-DNA level, transcriptomics,
      epigenomics, proteomics, ncRNomics, interactomics, metabolomics, glycomics,
      lipidomics, phenomics, environmental omics, pharmacogenomics, and integromics. We
      discussed characteristics of studies from different landscapes, such as main
      findings, number of participants, sample type, methodology, and outcome. We also
      performed curation and preliminary synthesis of multiple omics data, and
      identified overlapping results, which could lead toward selection of biomarkers
      for further validation of PD risk loci. Biomarkers could support the development
      of targeted prognostic/diagnostic panels as a tool for early diagnosis and
      prediction of progression rate and prognosis. This review presents an example of
      a comprehensive approach to revealing the underlying processes and risk factors
      of a complex disease. It urges scientists to structure the already known data and
      integrate it into a meaningful context.

PMID- 29356627
TI  - Rebooting Bioresilience: A Multi-OMICS Approach to Tackle Global Catastrophic
      Biological Risks and Next-Generation Biothreats.
AB  - Global Catastrophic Biological Risks (GCBRs) refer to biological events-natural,
      deliberate, and accidental-of a global and lasting impact. This challenges the
      life scientists to raise their game on two hitherto neglected innovation
      frontiers: a veritable "futures" thinking to "think the unthinkable," and
      "systems thinking" so as to see both the trees and the forest when it comes to
      GCBRs. This innovation analysis article outlines the promise of Omics systems
      science biotechnologies, for example, to deploy rapid fire diagnostics for health
      security crises at GCBR level, possibly involving neopathogens and/or incurring
      epidemics (e.g., severe acute respiratory syndrome [SARS] and Ebola) that
      collectively threaten the lives of global society and interdependent biological
      ecosystems. Moreover, Omics encourages thinking beyond immediacy and in long-term
      strategies for biopreparedness and response innovation when the timelines are
      aggressive and compressed in response to crises such as GCBRs, but also to non
      global but surging, multiple threats occurring as successive, overlapping, or
      distinct events, rather than as distinct entities-a prospect enforcing a reboot
      in Bioresilience. We define Next-Generation Bioresilience as "a systems approach
      against natural, accidental and perpetrated GCBRs using Omics technologies, and a
      shift in mentality, whereby the systems approach is expanded to include multiple
      plausible futures and expose unchecked assumptions attendant to risks, beyond
      technological determinism." In sum, it is time to think about the realistic
      potential of Omics biotechnologies beyond clinical practice and precision
      medicine so as to harness the opportunities and address the uncertainties
      associated not only with GCBRs but also with other emerging Omics applications in
      health and society.

PMID- 29356628
TI  - Proteomics of the Human Olfactory Tract.
AB  - Human olfactory tract plays a fundamental role in health and disease. Proteomic
      analysis of the olfactory tract therefore bears fundamental importance for
      integrative biology and clinical medicine. For example, olfactory dysfunction is
      one of the earliest findings in neurodegenerative disorders. The objective of the
      present study was to build the proteome data from human olfactory tract using a
      mass spectrometry-based approach. We performed a shotgun proteomic analysis of
      the human olfactory tract obtained from three healthy adult male subjects. The
      proteomics workflow consisted of fractionation based on high pH reverse phase
      liquid chromatography and SDS-PAGE, followed by liquid chromatography tandem-mass
      spectrometry (LC-MS/MS) analysis on high-resolution mass spectrometer. In total,
      6055 proteins were identified, which were further subjected to bioinformatics
      analysis and contextualization to identify the associated biological processes
      and molecular functions. We found the identified proteins involved in processes
      and functions related to olfactory perception, cell to cell adhesion, cellular
      and G-coupled receptor activity, axonal growth, and transportation. Importantly,
      we report the identification of 83 olfactory tract-restricted proteins, 4 seven
      transmembrane proteins, and 14 protein kinases. Pathway analysis of the
      restricted proteins revealed the enrichment of olfactory transduction, adherens
      junction, taste transduction, and neurotropic signaling pathways. To the best of
      our knowledge, this is the first study to report the human olfactory tract
      proteome. The study contributes to the knowledge of the human brain proteome and
      forms a crucial knowledge base for future applications in basic and clinical
      research, especially in olfactory sensation and neurodegenerative human
      disorders.

PMID- 29356629
TI  - Immediate Allergic Reactions to Gadolinium-based Contrast Agents: A Systematic
      Review and Meta-Analysis.

PMID- 29356630
TI  - Quantitative Imaging: The Translation from Research Tool to Clinical Practice.

PMID- 29356631
TI  - Does Texture Analysis of MR Images of Breast Tumors Help Predict Response to
      Treatment?

PMID- 29356633
TI  - Case 254.

PMID- 29356632
TI  - Lost Opportunities: Radiologists Are Not Sufficiently Using Reduced-Dose CT for
      Kidney Stones.

PMID- 29356635
TI  - Clinical Applicability of Deep Learning System in Detecting Tuberculosis with
      Chest Radiography.

PMID- 29356636
TI  - Recall Rate Benchmark for Screening Breast MR Imaging in Community Practice.

PMID- 29356634
TI  - Radiotheranostics in Cancer Diagnosis and Management.
AB  - The fundamental foundation for precision medicine is accurate and specific
      targeting of cancer cells. Advances in the understanding of cancer biology,
      developments in diagnostic technologies, and expansion of therapeutic options
      have all contributed to the concept of personalized cancer care. Theranostics is
      the systematic integration of targeted diagnostics and therapeutics. The
      theranostic platform includes an imaging component that "sees" the lesions
      followed by administration of the companion therapy agent that "treats" the same
      lesions. This strategy leads to enhanced therapy efficacy, manageable adverse
      events, improved patient outcome, and lower overall costs. Radiotheranostics
      refers to the use of radionuclides for the paired imaging and therapy agents.
      Radioiodine is the classic radiotheranostic agent that has been used clinically
      in management of thyroid diseases for nearly 75 years. More recently there have
      been major exciting strides in radiotheranostics for neuroendocrine tumors and
      prostate cancer, among other conditions. Regulatory approval of a number of
      radiotheranostic pairs is anticipated in the near future. Continued support will
      be needed in research and development to keep pace with the current momentum in
      radiotheranostics innovations. Moreover, regulatory and reimbursement agencies
      need to streamline their requirements for seamless transfer of the
      radiotheranostic agents from the bench to the bedside. In this review, the
      concept, history, recent developments, current challenges, and outlook for
      radiotheranostics in the treatment of patients with cancer will be discussed. (c)
      RSNA, 2018.

PMID- 29356637
TI  - Contribution of Bone Calcium to Bone Mineral Density.

PMID- 29356638
TI  - Quantitative MR Imaging Is Increasingly Important in Liver Disease.

PMID- 29356639
TI  - Diagnostic Ability with Abbreviated Biparametric and Full Multiparametric
      Prostate MR Imaging: Is the Use of PI-RADS Version 2 Appropriate for Comparison?

PMID- 29356640
TI  - Is Noise in the MR Imager a Significant Risk Factor for Hearing Loss?

PMID- 29356641
TI  - Shoulder Injuries in the Overhead-Throwing Athlete: Epidemiology, Mechanisms of
      Injury, and Imaging Findings.
AB  - The unparalleled velocity achieved by overhead throwers subjects the shoulder to
      extreme forces, resulting in both adaptive changes and pathologic findings that
      can be detected at imaging. A key biomechanical principle of throwing is
      achieving maximum external rotation, which initially leads to adaptive changes
      that may result in a pathologic cascade of injuries. In addition to the well
      established concepts of glenohumeral internal rotation deficit and internal
      impingement, osseous and soft-tissue injuries of the shoulder unique to overhead
      athletes are illustrated. The epidemiology and biomechanics of throwing injuries
      are reviewed, and examples from the authors' institutional experience with
      competitive, collegiate, and professional baseball players are provided to
      demonstrate the constellation of unique imaging findings seen in overhead
      throwing athletes. Given the widespread popularity of baseball, and other sports
      relying on overhead throwing motions at all playing levels from recreational to
      professional, it is important for radiologists in various practice settings to be
      familiar with the special mechanisms, locations, and types of shoulder injuries
      seen in the overhead throwing population. (c) RSNA, 2018.

PMID- 29356642
TI  - Choosing the Safest Gadolinium-based Contrast Medium for MR Imaging: Not So
      Simple after All.

PMID- 29356643
TI  - Seymour H. Levitt, MD.

PMID- 29356644
TI  - Absence of Cortical Vein Opacification is Associated with Lack of Intra-arterial
      Therapy Benefit in Stroke.

PMID- 29356645
TI  - Beyond BI-RADS Density: A Call for Quantification in the Breast Imaging Clinic.

PMID- 29356646
TI  - Science to Practice: Decrypting the Enigma of Ablation-induced Off-Target Effects
      Is Network Pathway Analysis the Final Piece of the Puzzle?
AB  - As part of the ongoing effort to better understand and mitigate pro-oncogenic off
      target effects of imaging-guided radiofrequency ablation (RFA), Kumar et al ( 1 )
      used gene expression and network pathway analysis to examine the gene activation
      profiles in the peri-ablational zone after RFA in a breast adenocarcinoma liver
      metastasis animal model. Their analysis identified STAT3 (signal transducer and
      activator of transcription 3) as a key transcription factor upregulated in many
      signaling pathways in the peri-ablational zone after RFA. Consequently, the
      authors successfully used two STAT3 inhibitors to reduce distant tumor growth
      after treatment with RFA. By demonstrating that judicious and appropriate
      adjuvant therapy helped contain distant tumor growth caused by ablation, Kumar et
      al have managed to pave the road ahead for the definitive success of ablation.

PMID- 29356647
TI  - Science to Practice: Will Gadolinium Chelates Be Replaced by Iron Chelates in MR
      Imaging?
AB  - Boehm-Sturm et al ( 1 ) pose a possible paradigm shift in magnetic resonance (MR)
      imaging: the substitution of iron chelates for gadolinium chelates as
      paramagnetic contrast agents. The advent of nephrogenic systemic fibrosis
      challenges the wide-spread perception that gadolinium is benign, and that all
      gadolinium-based contrast agents (GBCAs) are identical. Long-term gadolinium
      retention in patients with normal renal function is now a disturbing fact. Unlike
      gadolinium, iron is an endogenous metal with a tightly regulated transport and
      storage mechanism. The question the article raises is therefore a compelling one.

PMID- 29356648
TI  - Case 250: Alpers-Huttenlocher Syndrome.
AB  - History A 10-year-old girl with global developmental delay and attention deficit
      hyperactivity disorder was transferred from an outside hospital because of
      confusion and multiple episodes of left face and arm jerking. Physical
      examination revealed normal muscle bulk, strength, and tone in the bilateral
      upper and lower extremities but insuppressible left arm and jaw twitching Lumbar
      puncture revealed no white or red blood cells, a normal glucose level of 55 mg/dL
      (3.0 mmol/L) (normal range, 50-80 mg/dL [2.8-4.4 mmol/L]), and an elevated
      protein level of 81.6 mg/dL (normal range, 15-60 mg/100 dL). A comprehensive
      metabolic panel revealed lactic acidosis. The patient was initially started on
      levetiracetam, phenobarbital, phenytoin, and topiramate for status epilepticus.
      Hepatic dysfunction was not present at initial admission but developed 2 months
      later, with an alanine aminotransferase level of 90-406 U/L (1.5-6.8 MUkat/L)
      (normal range, 8-37 U/L [0.13-0.62 MUkat/L]) and aspartate aminotransferase in
      the range of 75-187 U/L (1.2-3.1 MUkat/L) (normal range, 8-35 U/L [0.13-0.58
      MUkat/L]). Electroencephalography revealed right parietal and occipital spike-and
      wave discharges, with bursts of up to 20 seconds, which were indicative of
      subclinical status epilepticus. The family history was remarkable for a sister
      with head lag, developmental delay, seizure disorder, and liver failure.

PMID- 29356649
TI  - Erosion of public health capacity should be a matter of concern for all
      Canadians.

PMID- 29356650
TI  - The association of exposure to suicide-related Internet content and emergency
      department visits in children: A population-based time series analysis.
AB  - OBJECTIVES: Suicide-related emergency department (ED) visits by children are
      increasing in tandem with suicide-related Internet content. Following the
      announcement of Amanda Todd's suicide, her YouTube video received widespread
      views, providing an opportunity to explore this association. METHODS: Our
      research question was: Among Ontario children age 11-17 years, was the release of
      Amanda Todd's YouTube video following her death announcement in October 2012
      associated with an increase in average monthly ED visit rates for suicide-related
      diagnoses? We performed an interrupted time series analysis from April 2002 to
      December 2013, with the primary outcome as a composite of the average monthly
      rate of initial ED visits for suicidal ideation, intentional self-poisoning, and
      intentional self-harm. Secondary outcomes were average monthly rates of intensive
      care unit (ICU) admission and death resulting from the index visit. RESULTS:
      There was a statistically significant increase in the monthly ED visit rate for
      the composite outcome (p = 0.02) and death or ICU admission (p = 0.006) from
      April 2002 to December 2013. There was no significant change in ED visit rate for
      the composite outcome before and after the announcement of Amanda Todd's death,
      overall (119.8 versus 219.2 respectively, p = 0.5), among females (167.4 versus
      316.8 respectively, p = 0.47) or among males (74.7 versus 116.9 respectively, p =
      0.33). CONCLUSIONS: Ontario ED visits for suicide-related diagnoses in 11-17 year
      olds increased from 2002 to 2013. However, the increase from October 2012 to
      December 2013 could not be attributed to a highly publicized adolescent suicide.
      Our findings suggest that suicide-related Internet content is not associated with
      the increase in ED visits for suicidal behaviour.

PMID- 29356651
TI  - Cyberbullying victimization and its association with health across the life
      course: A Canadian population study.
AB  - OBJECTIVES: To examine the prevalence of cyberbullying victimization (CV), its
      associations with self-reported health and substance use and the extent to which
      age moderates these associations. METHODS: We used the 2014 Canadian General
      Social Survey on Victimization (N = 31 907, mean age = 45.83, SD = 18.67) and
      binary logistic regression models to estimate the strength of association between
      CV and health-related outcomes. RESULTS: The five-year prevalence of CV was 5.1%.
      Adolescents reported the highest prevalence of CV (12.2%), compared to all other
      adult age groups (1.7%-10.4%). After controlling for socio-demographic
      covariates, individuals exposed to CV had increased odds of reporting poor mental
      health (OR = 4.259, 95% CI = 2.853-6.356), everyday limitations due to mental
      health problems (OR = 3.263, 95% CI = 2.271-4.688), binge drinking (OR = 2.897,
      95% CI = 1.765-4.754), and drug use (OR = 3.348, 95% CI = 2.333-4.804), compared
      to those not exposed to CV. The associations between CV and self-reported mental
      health and substance use were strongest for adolescents and attenuated across the
      adult age groups. CONCLUSION: Adolescence may represent a developmental period of
      heightened susceptibility to CV. Developing and evaluating targeted preventive
      interventions for this age group is warranted.

PMID- 29356652
TI  - Cybervictimization among preadolescents in a community-based sample in Canada:
      Prevalence and predictors.
AB  - OBJECTIVES: To examine the prevalence and predictors associated with
      cybervictimization among preadolescents in a community-based sample from Canada.
      METHODS: Data were drawn from a cohort of 5783 students of grades 5-8, aged 9-14
      from 109 elementary schools at the Saskatoon Health Region, Saskatchewan of
      Canada based on the Student Health Survey in the year of 2010-2011. Multivariate
      logistic regression with the generalized estimating equation was used to
      determine the individual and contextual factors associated with self-reported
      cybervictimization. RESULTS: Of the 5783 school children, 5611 (97.0%) responded
      to the question regarding cybervictimization. Among those respondents, 572
      (10.2%) reported being cyberbullied at least once in the past four weeks. The
      students most likely to be victimized by cyberbullying were girls, students in
      grades 7 and 8 compared with grade 5, Aboriginal students compared to non
      Aboriginal students, those who had lived part of their life outside of Canada
      compared with those who lived all of their life in Canada, those who reported
      drinking alcohol in the past, those who reported very elevated depressive
      symptoms, those who were traditionally bullied, those who had low self-esteem,
      and those who had a poor relationship with their parents. School-level variation
      in cyberbullying victimization is negligible. School neighbour-level deprivation
      is not significant after adjusting for individual-level characteristics and
      parent-child relationship. CONCLUSION: Our findings identified important
      characteristics of preadolescents with higher susceptibility to
      cybervictimization in a Canadian setting, which can be used to develop
      intervention strategies for mitigating cybervictimization among the study
      population.

PMID- 29356654
TI  - Alcohol distribution reforms and school proximity to liquor sales outlets in New
      Brunswick.
AB  - OBJECTIVES: The purpose of this project was to evaluate how changes to the sale
      of alcohol in New Brunswick would be distributed across urban and rural
      communities, and low- and high-income neighbourhoods. The study objectives were
      to 1) estimate the population living close to alcohol outlets before and after
      liquor distribution reforms, 2) identify communities or regions that would be
      more or less affected, and 3) determine whether expanding access to alcohol
      products would reduce school proximity to retailers. METHODS: Data from
      Statistics Canada, Desktop Mapping Technologies Inc. (DMTI), and geocoded
      publicly available information were spatially linked and analyzed using
      descriptive statistics. The populations living within 499 m, 500-999 m and 1-5 km
      of an outlet were estimated, and the distances from schools to stores were
      examined by geographic characteristics and neighbourhood socio-economic status.
      RESULTS: Permitting the sale of alcohol in all grocery stores throughout the
      province would increase the number of liquor outlets from 153 to 282 and would
      increase the population residing within 499 m of an outlet by 97.49%, from 19 886
      to 39 273 residents. The sale of alcohol in grocery stores would result in an
      additional 35 liquor sales outlets being located within 499 m of schools. Low
      income neighbourhoods would have the highest number and proportion of stores
      within 499 m of schools. CONCLUSION: The findings of this study demonstrate the
      importance of considering social, economic and health inequities in the context
      of alcohol policy reforms that will disproportionately affect low-income
      neighbourhoods and youth living within these areas.

PMID- 29356653
TI  - Racial discrimination and depression among on-reserve First Nations people in
      rural Saskatchewan.
AB  - OBJECTIVES: To determine among rural-dwelling on-reserve Saskatchewan First
      Nations people whether racial discrimination is associated with depression, and
      in turn, if this relationship is moderated by gender. METHODS: As a component of
      a community-based participatory research project, a cross-sectional, interviewer
      administered survey of 874 adults living on 2 Cree First Nation reserves in rural
      north-central Saskatchewan was conducted during May-August in 2012 and 2013. Self
      reported, health-provider diagnosis of depression was the dependent variable and
      experiences of interpersonal racial discrimination was the primary exposure. Chi
      square and multiple logistic regression were the main analytic techniques.
      Generalized estimating equations were applied to account for clustering within
      households. RESULTS: Overall, 64% of participants reported being treated unfairly
      in 1 or more situations because of their ethnicity; 38% indicated discrimination
      occurring in 3 or more situations. Nineteen percent reported a diagnosis of
      depression. Adjusted analyses indicated that compared to those with no experience
      of racial discrimination, those reporting 1-2 and 3 or more situations were 1.77
      times (95% CI: 1.06-2.95) and 1.91 times (95% CI: 1.19-3.04) more likely to have
      diagnosed depression respectively. The relationship between racial discrimination
      and depression was not modified by gender, although women were 1.85 times (95%
      CI: 1.24-2.76) more likely to report depression than men. CONCLUSION:
      Interpersonal racial discrimination was associated with depression among First
      Nations women and men in rural Saskatchewan. Research directed at identifying the
      most efficacious interventions, programs and policies to combat racism is
      required to advance the goal of health equity.

PMID- 29356655
TI  - Difficulty buying food, BMI, and eating habits in young children.
AB  - OBJECTIVES: To determine whether parent report of difficulty buying food was
      associated with child body mass index (BMI) z-score or with eating habits in
      young children. METHODS: This was a cross-sectional study in primary care offices
      in Toronto, Ontario. Subjects were children aged 1-5 years and their caregivers,
      recruited through the TARGet Kids! Research Network from July 2008 to August
      2011. Regression models were developed to test the association between parent
      report of difficulty buying food because of cost and the following outcomes:
      child BMI z-score, parent's report of child's intake of fruit and vegetables,
      fruit juice and sweetened beverages, and fast food. Confounders included child's
      age, sex, birth weight, maternal BMI, education, ethnicity, immigration status,
      and neighbourhood income. RESULTS: The study sample consisted of 3333 children.
      Data on difficulty buying food were available for 3099 children, and 431 of these
      (13.9%) were from households reporting difficulty buying food. There was no
      association with child BMI z-score (p = 0.86). Children from households reporting
      difficulty buying food (compared with never having difficulty buying food) had
      increased odds of consuming three or fewer servings of fruits and vegetables per
      day (odds ratio [OR]: 1.31, 95% confidence interval [CI]: 1.03-1.69), more than
      one serving of fruit juice/sweetened beverage per day (OR: 1.60, 95% CI: 1.28
      2.00), and, among children 1-2 years old, one or more servings of fast food per
      week (OR: 2.91, 95% CI: 1.67-5.08). CONCLUSION: Parental report of difficulty
      buying food is associated with less optimal eating habits in children but not
      with BMI z-score.

PMID- 29356656
TI  - Socio-economic inequalities in exposure to industrial air pollution emissions in
      Quebec public schools.
AB  - OBJECTIVES: We aimed to assess the relationships between deprivation at Quebec
      public schools, their proximity to polluting industries, and their exposure to
      industrial air emission sources including ambient fine particulate matter
      (PM2.5), sulphur dioxide (SO2) and nitrogen dioxide (NO2). METHODS: We obtained
      four indicators of school deprivation using data from the 2006 Canadian census
      called the low-income threshold indicator, the neighbourhood SES indicator, and
      the social and material deprivation indicators of Pampalon. Using proximity
      spatial tools, we constructed three buffers of 2.5, 5 and 7.5 km around each
      school and summed up total emissions of PM2.5, SO2 and NO2 for each school.
      Industrial air emissions were estimated using data from the 2006 Canadian
      National Pollutant Release Inventory. The Pearson correlations and LOESS
      regressions and natural log-transformed industrial air emissions were evaluated
      for Quebec public schools within the three buffers. RESULTS: Of the 2189 public
      schools in Quebec, 608 (27.8%), 1108 (50.6%) and 1384 (63.2%) schools were
      located near at least one industry emitting one or more pollutants of interest in
      buffers of 2.5 km, 5 km and 7.5 km of schools respectively. Weak positive Pearson
      correlations (r) were found between log-transformed tons of industrial emissions
      of PM2.5, SO2 and NO2 and both the social deprivation (r = {0.23; 0.33}) and low
      income threshold (r = {0.17; 0.29}) indicators in a buffer of 2.5 km. However, we
      found negative associations between emissions and the neighbourhood SES (r =
      {0.06; 0.16}) and material deprivation (r = {-0.04; 0.08}) indicators.
      CONCLUSION: Our study suggests that schools in Quebec with higher rates of socio
      economic deprivation among their students may be more likely to be exposed to
      higher emissions of industrial air pollutants.

PMID- 29356657
TI  - ?
AB  - OBJECTIF: Examiner le lien entre les conditions de travail et la sante mentale
      des travailleurs-euses de la restauration.METHODE : L'echantillon se compose de
      652 travailleurs-euses de la restauration issus de l'ESCC-SM de 2012. Des
      analyses de regression lineaire hierarchique sont effectuees et ajustees en
      fonction de divers facteurs selectionnes (sociodemographiques, habitudes de vie).
      Les conditions de travail sont mesurees en partie selon le Job Content
      Questionnaire (JCQ) de Karasek et Theorell. La detresse psychologique est mesuree
      a partir de l'echelle K6 de Kessler. La sante mentale positive est mesuree a
      partir du Continuum de sante mentale-version abregee (MHC-SF) de Keyes.RESULTATS
      : Les fortes exigences psychologiques, le travail a temps partiel et les fortes
      exigences physiques sont associes de facon positive a la detresse psychologique
      des travailleurs-euses de la restauration, alors que le soutien social des
      collegues y est associe de facon inverse. Pour la sante mentale positive des
      travailleurs-euses de la restauration, l'insecurite d'emploi, les fortes
      exigences psychologiques et la faible latitude decisionnelle sont associees de
      facon negative tandis que le soutien social des collegues y est associe
      inversement. CONCLUSION: Cette etude souligne l'importance de considerer a la
      fois les aspects positifs et negatifs de la sante mentale. En effet, les facteurs
      associes a la sante mentale positive et a la detresse psychologique des
      travailleurs-euses de la restauration sont differents, voire associes en
      direction inverse.

PMID- 29356658
TI  - Prevalence of problematic cannabis use in Canada: Cross-sectional findings from
      the 2013 Canadian Tobacco, Alcohol and Drugs Survey.
AB  - OBJECTIVES: Cannabis is the most widely used illicit substance in Canada. There
      exist a variety of tools to measure problematic characteristics of cannabis use;
      however, there is no consensus on the operational definition of "problematic
      use". The current study sought to estimate the prevalence of problematic cannabis
      use in Canada, in terms of the kinds of problems Canadians report due to their
      cannabis use, the levels of harm associated with cannabis consumption, and
      potential differences among socio-demographic groups. METHODS: Cross-sectional,
      nationally representative data for Canadians were obtained from the publicly
      available Statistics Canada's 2013 Canadian Tobacco, Alcohol and Drugs Survey
      (CTADS) (n = 13 635). Binary logistic regression analyses were conducted to
      examine subgroup differences in patterns of cannabis use and problematic outcomes
      defined by the World Health Organization's Alcohol, Smoking and Substance
      Involvement Screening Test (ASSIST) tool embedded in CTADS. RESULTS: The findings
      indicate that, while 1 in 10 Canadians reported using cannabis in the past 3
      months, only 2% of the sample of Canadians who reported using cannabis in the
      past 3 months were characterized as having a "high risk" of severe health or
      other problems. Canadian male respondents were more likely to report social
      problems than females and to be categorized as high risk. Youth and young adults
      between the ages of 15 and 29 consistently reported a greater prevalence of
      problems associated with their cannabis consumption than their older
      counterparts. CONCLUSION: A very small proportion of Canadians report using
      cannabis to a degree that is problematic. Approximately one in two young people
      reported using cannabis at some point in their lives, of concern given the
      negative health outcomes of early cannabis use. This study highlights the need
      for the development of more sensitive instruments to detect problematic cannabis
      use.

PMID- 29356659
TI  - Proximity to two main sources of industrial outdoor air pollution and emergency
      department visits for childhood asthma in Edmonton, Canada.
AB  - OBJECTIVE: Children are recognized to be more susceptible than healthy adults to
      the effects of air pollution; however, relatively few Canadian studies of
      children have focused on industrial emissions. We conducted a spatial cross
      sectional study to explore associations between emergency department (ED) visits
      for childhood asthma and residential proximity to two industrial sources of air
      pollution (coal-fired power plant and petrochemical industry) in Edmonton,
      Canada. METHODS: Using administrative health care data for Alberta between 2004
      and 2010, we conducted a spatial analysis of disease clusters of count data
      around these two industrial sources. The distance from children's place of
      residence to these industrial sources was determined by using the six-character
      postal code from the children's ED visit. Clusters of cases were identified at
      the census dissemination area. Negative binomial multivariable spatial regression
      was used to estimate the risks of clusters in relation to the distance to these
      industrial sources. RESULTS: The relative risk of ED visits for asthma,
      calculated using a spatial scan test for events, was 10.4 (p value <0.01) within
      the power plant area when compared with the outside area. In addition, there was
      an inverse association of the distance to the power plant (coefficient = -0.01
      per km) with asthma visits when multivariable models were used. No asthma
      clusters were identified around the petrochemical industrial area. CONCLUSION:
      Our analyses revealed that there was a cluster of ED visits for asthma among
      children who lived near the coal-fired power plant just outside Edmonton.

PMID- 29356660
TI  - Validating an administrative data-based case definition for identifying children
      and youth with autism spectrum disorder for surveillance purposes.
AB  - OBJECTIVES: To evaluate the sensitivity and positive predictive value (PPV) of
      administrative health and education data for identifying cases of autism spectrum
      disorder (ASD) in Manitoba, and to recommend a surveillance case definition.
      METHODS: Four service providers abstracted information on children who had been
      clinically diagnosed with ASD ("sensitivity cohort"). That information was linked
      to Manitoba's administrative health and education data and records were extracted
      into the study dataset. Records were also included for children who had an
      administrative diagnosis of ASD but who were not part of the sensitivity cohort.
      Study packages were mailed to the parents of the latter group in order to verify
      their diagnostic status. The sensitivity and PPV of various case definitions were
      calculated. RESULTS: Among the 1728 service provider-reported cases, 1532 had an
      administrative diagnosis of ASD. A total of 2414 children had an administrative
      diagnosis, of whom 882 were not part of the sensitivity cohort. The response to
      the mail-out was very poor (<3%). Accordingly, we calculated minimum PPVs. Our
      recommended surveillance case definitions are >=1 physician claim (ICD-9-CM 299)
      or >=1 "ASD" special education record (2-5 years of age), and >=2 physician
      claims or >=1 "ASD" special education record (6-14 years of age). The sensitivity
      ranged from 80% (95% CI: 77-83) to 88% (95% CI: 83-91) and the minimum PPV from
      70% (95% CI: 67-73) to 78% (95% CI: 75-81) for these definitions. CONCLUSION:
      This work advances the goal of establishing a cost-effective national
      surveillance system for ASD.

PMID- 29356661
TI  - The impact of false positive breast cancer screening mammograms on screening
      retention: A retrospective population cohort study in Alberta, Canada.
AB  - OBJECTIVES: The impact of false positives on breast cancer screening retention is
      inconsistent across international studies. We investigate factors associated with
      screening retention, including false positive screening results, invasiveness of
      diagnostic procedures, and geographic variation in Alberta, Canada. METHODS: A
      total of 213 867 women aged 50-67 years who had an index screen mammogram between
      July 2006 and June 2008 were evaluated at 30 months post index screen to
      determine the screening retention rate. The association of screening retention
      with invasiveness of the diagnostic procedure, time to diagnostic resolution, and
      region of residence were investigated using multivariable log binomial
      regression, adjusting for women's age. RESULTS: Women with false positive
      screening results were less likely to return for their next recommended screening
      than those with a true negative result (62.0% vs. 68.7%). Compared to women with
      normal screening results, the adjusted risk ratios of fail-to-rescreen for women
      with imaging-only follow-up, needle sampling, and open biopsy were 1.08 (95% CI:
      1.05-1.12), 1.72 (95% CI: 1.44-2.07) and 2.29 (95% CI: 2.09-2.50) respectively.
      Screening retention rates were slightly higher for rural residents than urban
      residents. Time to diagnostic resolution was not associated with screening
      retention. Screening retention peaked at one year from the index date of the
      previous screening. CONCLUSION: Higher awareness of the strong negative impact
      that biopsies in the case of a false positive screening have on screening
      retention is needed. Such awareness can inform intervention strategies to
      mitigate the impact and improve screening retention rate.

PMID- 29356662
TI  - Does socio-economic status or having a chronic condition affect whether family
      physicians accept a new patient? A Nova Scotia population study.
AB  - OBJECTIVES: To determine whether socio-economic status (SES) and presence of a
      chronic condition are associated with the response a prospective patient receives
      when seeking a family physician (FP). METHODS: Scripted telephone calls
      (indicating higher or lower SES and presence or absence of a chronic condition)
      were made to all 327 FP offices in Nova Scotia (NS) requesting an appointment.
      The main outcome measures were the responses to callers seeking a FP: being
      accepted for an appointment or being offered further assistance if not accepted
      (e.g., walk-in clinic, alternative provider, and telehealth), as well as the
      callers' perception of the experience as positive, negative, or neutral. RESULTS:
      Only 9.9% of offices accepted callers as new patients. There were no
      statistically significant differences by SES or chronic condition in the
      proportion of calls resulting in an appointment. Callers indicating high SES were
      more likely to be provided further assistance than those with low SES (p = 0.06),
      and callers indicating a chronic condition reported a better overall experience
      than those without (p = 0.03). CONCLUSION: First contact accessibility for
      prospective new patients was low across NS. Lower SES was associated with fewer
      offers of additional assistance than higher SES. This is particularly troubling
      since those with lower SES may need additional support as they may have less
      access to resources and networks that could provide support. This study signals
      the need to improve general and equitable accessibility to primary care
      providers.

PMID- 29356663
TI  - Active living in Saskatchewan: A review of official community plans.
AB  - OBJECTIVE: Municipal policies may have a significant impact on the development of
      environments that provide sustainable opportunities for individuals to engage in
      healthy, active lifestyles. Little is known about how explicitly community
      planning in Canada integrates strategies to promote physical activity. In the
      context of Active Saskatchewan 2020 (AS2020), the strategic plan of Saskatchewan
      in motion, such an analysis would create a basis for identifying policy gaps and
      ongoing monitoring. The objective of this study was to review the official
      community plan (OCP) of each city in the province of Saskatchewan, Canada and
      identify policies supportive of physical activity. METHODS: A conventional
      content analysis was completed of the OCPs of the 17 cities in Saskatchewan. Each
      OCP was reviewed and text extracted that related to supporting physical activity.
      Extracted text was thematically organized within and across cities, creating a
      set of indicators for ongoing monitoring. RESULTS: Overall, 17 indicators were
      identified. The frequency of inclusion of these indicators within the 17 OCPs
      varied from 17.6% to 82.4%. The mean frequency of indicators identified per OCP
      was 7.4. The most commonly included indicators included residential neighbourhood
      plans associated with active living, downtown cycling and pedestrian plans, and
      joint-use agreements between communities and schools. CONCLUSIONS: Most
      Saskatchewan OCPs make little direct reference to policies supportive of physical
      activity. Impacting community-level policy is an expected outcome of
      AS2020/Saskatchewan in motion. This study identifies a range of indicators for
      monitoring this process and highlights potential areas for policy development
      within OCPs.

PMID- 29356664
TI  - Geographic variation and factors associated with colorectal cancer incidence in
      Manitoba.
AB  - OBJECTIVES: Although individuals living in areas with lower household income have
      been shown to have higher rates of mortality from colorectal cancer (CRC),
      findings on the effect of income on CRC incidence in countries with universal
      health care have been inconsistent. There are limited data from Canada. We
      investigated the geographic variation and factors associated with CRC incidence
      in Manitoba, a central Canadian province. METHODS: The Manitoba Cancer Registry
      and Manitoba Health population registry were used to determine age-sex
      standardized CRC incidence rates between 1985 and 2012, which were geocoded to
      498 small geographic areas (SGAs). The 2001 Canadian Census was used to determine
      the socio-demographic characteristics of the SGAs. Bayesian spatial Poisson
      modelling was used to assess geographic variation and factors associated with CRC
      incidence. RESULTS: CRC incidence in SGAs ranged from 11 to 1026 per 100 000
      population per year. Importantly, in the fully adjusted model there was no
      significant association between either average household income or proportion of
      recent immigrants in the SGAs and CRC incidence. Individuals living in urban
      areas had an overall lower CRC incidence (incidence rate ratio: 0.76; 95%
      credible interval: 0.58-0.98). CONCLUSIONS: In a province with a universal health
      care system, our study suggests there are no disparities in CRC incidence by
      socio-economic level of the areas of residence. Rural areas should be a focus of
      CRC reduction initiatives in Manitoba. Similar analysis in other jurisdictions
      should be performed to evaluate the effect of the characteristics of SGAs on CRC
      incidence in different settings and target some of the efforts to reduce CRC
      burden.

PMID- 29356665
TI  - Slim cigarette smoking prevalence among Canadian youth smokers: Implications for
      federal standardized packaging legislation.
AB  - OBJECTIVES: Tobacco companies market to females and young people through slim
      cigarette design features and packaging. This study assessed the prevalence and
      perceptions of slim cigarette smoking in grades 9-12 student smokers across
      Canada using multiple data sources. METHODS: Data from three cycles of the Youth
      Smoking Survey (2008/2009 to 2012/2013) and one cycle of the Cancer Risk
      Assessment in Youth Survey (2015) were used. The prevalence and perceptions of
      slim cigarette smoking among current smokers were compared by sex and grade.
      RESULTS: In all surveys, the rate of slim cigarette use was higher among females
      than males; however, this difference was not statistically significant. In the
      two most recent surveys, grades 9-10 students had a significantly higher
      prevalence of use compared with grades 11-12 students. The majority of students
      (59.8% of females and 53.3% of males) responded, "I don't know" to the survey
      item seeking to determine perceptions of harm of slim cigarettes compared with
      regular cigarettes. CONCLUSION: Slim cigarette use among Canadian grades 9-12
      students represents a small but growing problem. Youths' uncertainty around the
      harms associated with slim cigarette use and the effect of slim cigarette
      packaging and design on harm perceptions indicate the need for product design
      regulations and further education in Canada.

PMID- 29356666
TI  - Factors associated with shorter night-time sleep in toddlers: The Survey of Young
      Canadians.
AB  - OBJECTIVES: Adequate sleep in childhood is important for healthy development. No
      information exists on the predictors of night-time sleep among toddlers in
      Canada. The aim of this study was to determine the prevalence of and to identify
      factors associated with sleeping <11 consecutive hours per night among children
      aged 1-2 years in Canada. METHODS: Data from the cross sectional Survey of Young
      Canadians (SYC) 2010 were used. The biological mother reported on toddlers' sleep
      duration at night. Based on cut-off values used in previous studies, shorter
      night-time sleep was defined as sleeping <11 hours per night. Multivariable
      logistic regression was conducted to identify the associations between socio
      demographic, maternal, sleep and child-related variables with shorter sleep at
      night. RESULTS: Analysis of 3675 toddlers revealed that 57% slept <11 hours per
      night. Results of the regression analysis showed that being from an
      immigrantfamily was significantly associated with shorter night-time sleep. Being
      from a higher income household, having a mother aged between 25 and 34 years at
      the time of the survey, and napping >=2 hours during the day were significantly
      related to sleeping >=11 hours per night. Other socio-demographic, maternal and
      child-related variables were not associated with night-time sleep. CONCLUSION:
      This was the first population-based, nationally representative study to examine
      factors related to shorter night-time sleep in Canadian toddlers. Socio
      demographic factors and nap duration were associated with night-time sleep
      duration. More adequate early childhood sleep hygiene awareness efforts are
      recommended, especially in vulnerable populations.

PMID- 29356667
TI  - Child development in rural Ghana: Associations between cognitive/language
      milestones and indicators of nutrition and stimulation of children under two
      years of age.
AB  - OBJECTIVES: Two studies aimed to assess the provision of nutrition and
      psychosocial stimulation in the home and to examine associations between mental
      development and nutrition and stimulation using a validated measure of
      development milestones. METHODS: The first study consisted of secondary analyses
      on health and nutrition data from 1081 mother-child pairs (the children aged 0-12
      months) and their households in Ghana's Eastern Region. For the second study, the
      Ghana Milestones Measure, consisting of items assessing cognitive and language
      development, was used to assess child development in a subsample (N = 330) of
      Study 1 participants one year later (children 10-24 months of age). This measure
      was mother-reported and had been validated in a separate community in Ghana.
      Correlation and linear regression analyses were used to analyze the data.
      RESULTS: Family assets and maternal education were identified as key factors of
      the family context. Both variables were positively associated with preventive
      health practices (r = 0.08 to 0.13, p < 0.0001 to 0.01), and dietary diversity (r
      = 0.15, p = 0.0001 to 0.0006), and negatively associated with maternal depressive
      symptoms (r = -0.19 to -0.12, p < 0.0001). Taller children had higher receptive
      (standardized beta = 0.16; p = 0.04) and expressive (0.21; 0.003) language, but
      not cognitive (0.15; 0.07) milestone scores, and psychosocial stimulation was
      positively associated with all three milestones (receptive = 0.13, p = 0.01;
      expressive = 0.21, p < 0.0001; and cognitive = 0.24, p < 0.0001). CONCLUSION: Our
      study provides the first validated measure of children's language and cognitive
      development in Ghana, finding associations with nutrition and stimulation. The
      Ghana Milestones Measure can be used to assess and help promote children's mental
      development.

PMID- 29356668
TI  - ?
AB  - OBJECTIFS: Evaluer le role des commodites familiales dans l'occurrence de la
      diarrhee chez les enfants de moins de 5 ans en Haiti, selon leur type (eau
      potable, toilettes et refrigerateur) et leur nombre.METHODE : Nous avons mis en
      commun les donnees de quatre Enquetes demographiques et de sante realisees en
      Haiti entre 1994-1995 et 2012. Nous avons retenu un echantillon de 14 481 enfants
      de 1-59 mois. Nous avons evalue le role des commodites familiales dans
      l'occurrence de la diarrhee selon le groupe d'age d'enfants a risque (1-5; 6-11;
      12-23; 24-59 mois), au moyen des modeles de regression logistique.RESULTATS : La
      prevalence de la diarrhee chez les enfants de 1-59 mois en Haiti est estimee a
      29,31 %. Elle atteint 42,14 % chez les enfants de 6-11 mois. Elle est plus faible
      pour les enfants dont les familles ont acces a une eau potable amelioree, des
      toilettes ameliorees ou un refrigerateur. Elle est d'autant plus faible que les
      familles possedent au moins deux commodites simultanement. Nous ne trouvons pas
      de differences significatives dans l'occurrence de la diarrhee infanto-juvenile
      selon l'acces a l'eau potable (p > 0,10). Prenant en compte l'effet de periode,
      une occurrence reduite de la diarrhee est significativement associee aux
      toilettes ameliorees chez les enfants de 24-59 mois (RC : 0,62; p < 0,05) et au
      refrigerateur chez les 6-11 mois (RC : 0,11; p < 0,05). Pour le nombre de
      commodites, seuls les 24-59 mois ayant au moins deux commodites ont une
      occurrence de la diarrhee statistiquement inferieure de celle des plus
      defavorises (RC : 0,45; p < 0,05). CONCLUSION: Augmenter l'acces aux commodites
      familiales et leur nombre par menage demeure essentiel dans la lutte contre la
      diarrhee en Haiti. Une intervention integree serait donc a preconiser dans
      l'environnement sociosanitaire haitien.

PMID- 29356669
TI  - A critical analysis of obesity prevention policies and strategies.
AB  - OBJECTIVES: Public health policies have been criticized for promoting a
      simplistic narrative that may contribute to weight bias. Weight bias can impact
      population health by increasing morbidity and mortality. The objectives of this
      study were to: 1) critically analyze Canadian obesity prevention policies and
      strategies to identify underlying dominant narratives; 2) deconstruct dominant
      narratives and consider the unintended consequences for people with obesity; and
      3) make recommendations to change dominant obesity narratives that may be
      contributing to weight bias. METHODS: We applied Bacchi's "what's-the-problem
      represented-to-be?" (WPR) approach to 15 obesity prevention policies and
      strategies (1 national, 2 territorial and 12 provincial). Bacchi's WPR approach
      is composed of six analytical questions designed to identify conceptual
      assumptions as well as possible effects of policies. RESULTS: We identified five
      prevailing narratives that may have implications for public health approaches and
      unintended consequences for people with obesity: 1) childhood obesity threatens
      the health of future generations and must be prevented; 2) obesity can be
      prevented through healthy eating and physical activity; 3) obesity is an
      individual behaviour problem; 4) achieving a healthy body weight should be a
      population health target; and 5) obesity is a risk factor for other chronic
      diseases, not a disease in itself. CONCLUSION: The consistent way in which
      obesity is constructed in Canadian policies and strategies may be contributing to
      weight bias in our society. We provide some recommendations for changing these
      narratives to prevent further weight bias and obesity stigma.

PMID- 29356670
TI  - Impact of the decision-making environment on policy responses to road worker
      fatality in Manitoba and Saskatchewan.
AB  - OBJECTIVES: Fatal accidents often lead to policy changes. However, the existing
      decision-making environment is critical to policy responses. This study compares
      the policy responses to similar events in Manitoba and Saskatchewan. The key
      question explores the extent to which the policy decisions in each province
      differ despite the similarity of the events. METHODS: Key documents were
      examined. Provincial court rulings, workplace health & safety incident
      investigation reports, court transcripts and police reports were used to compare
      resulting policy changes as well as the socio-political and economic decision
      making context. Relevant clauses in resulting legislation were also compared to
      assess the specific changes that were made in each province. RESULTS: In each
      province, a young, female highway construction worker was killed. However, the
      provinces responded in very different ways. In Saskatchewan, the Premier called
      for recommendations to improve worker safety, initiating an in-depth governmental
      study and the development of a broad safety strategy. In Manitoba, political and
      social pressures shifted the decision-making environment and contributed to the
      rushed passing of a bill focused on traffic fine increases that resulted in
      record-breaking traffic fine revenue while failing to include broader safety
      measures. CONCLUSION: Different decision-making contexts can lead to vastly
      different policy outcomes even when responding to very similar events. Key
      differences included time constraints, access to information and the nature of
      the political process invoked.

PMID- 29356671
TI  - Opioid use in pregnancy and parenting: An Indigenous-based, collaborative
      framework for Northwestern Ontario.
AB  - Opioid use affects up to 30% of pregnancies in Northwestern Ontario. Health care
      providers in Northwestern Ontario have varying comfort levels providing care to
      substance-involved pregnant women. Furthermore, health care practitioners, social
      service agencies and community groups in Northwestern Ontario often work in
      isolation with little multidisciplinary communication and collaboration. This
      article describes two workshops that brought together health and social service
      providers, community organizations, as well as academic institutions and
      professional organizations involved in the care of substance-involved pregnant
      and parenting women. The initial workshop presented best practices and local
      experience in the management of opioid dependence in pregnancy while the second
      workshop asked participants to apply a local Indigenous worldview to the
      implementation of clinical, research and program priorities that were identified
      in the first workshop. Consensus statements developed by workshop participants
      identified improved transitions in care, facilitated access to buprenorphine
      treatment, stable funding models for addiction programs and a focus on Indigenous
      led programming. Participants identified a critical need for a national strategy
      to address the effects of opioid use in pregnancy from a culturally safe, trauma
      informed perspective that takes into account the health and well-being of the
      woman, her infant, her family and her community.

PMID- 29356672
TI  - ?
AB  - Un Centre de services sociaux et de sante (CSSS) de Montreal a mis en place une
      communaute d'apprentissage des formateurs suite a la visite d'agrement relie a
      l'obtention de la certification Initiative Amis des bebes. Les evaluatrices de ce
      programme de qualite de soins avaient note que les parents retenaient peu
      l'information transmise lors des rencontres prenatales. L'article decrit le
      dispositif de developpement professionnel etabli aupres de l'equipe de
      perinatalite qui cherchait a ameliorer ses pratiques d'enseignement. Il resume
      aussi les deux evaluations qui ont soutenu de facon continue le perfectionnement
      des professionnelles. La discussion porte sur les conditions les plus
      susceptibles d'avoir favorise leur developpement des competences en enseignement.
      Il ressort notamment que les parents retiennent des informations et les
      appliquent lorsque les professionnelles reussissent a les rendre actifs et a les
      toucher emotivement dans leur apprentissage : le contact peau a peau et le
      renforcement des objectifs d'allaitement en sont des exemples eloquents.

PMID- 29356673
TI  - Stories of policy change: City of Hamilton's healthy food and beverage policy.
AB  - SETTING: Municipal buildings and corporate events in the City of Hamilton,
      Ontario. INTERVENTION: In 2011, the City of Hamilton adopted a healthy food and
      beverage policy. The intent of the policy is to demonstrate the City's commitment
      to healthy eating by providing food and beverages that are healthy, safe, and
      free of industrially produced trans fats, and promoting a sustainable, local food
      system. The corporate policy applies to all City facilities, meetings and events.
      In this article, we explore adoption and implementation of the policy, as well as
      key lessons for healthy public policy change. OUTCOMES: Integrating the policy
      into corporate culture and practice through the provision of ongoing supports and
      resources helped the City of Hamilton overcome barriers and achieve
      implementation success. IMPLICATIONS: Through exploration of the City of
      Hamilton's healthy food and beverage policy, we identified a number of lessons
      for policy change and implementation. When viewed in context, these lessons may
      help to support policy work in other Canadian jurisdictions.

PMID- 29356674
TI  - A response to "A critical analysis of obesity prevention policies and
      strategies".
AB  - This commentary provides a response to the article "A critical analysis of
      obesity prevention policies and strategies" from a feminist fat studies
      perspective. We argue that a fundamental disjuncture exists between the authors'
      desire to redress fat stigma, and their understanding of "obesity as disease",
      which inherently draws on a neoliberal, healthist paradigm of health and body
      weight that is at the root of fat stigma.

PMID- 29356675
TI  - And if there were another way out? Questioning the prevalent radicalization
      models.
AB  - Violent radicalization is increasingly conceptualized as a public health issue,
      associated with psychological distress, a sharp increase in discrimination and
      profiling, and an increase in hate crime and some types of terrorist acts.This
      brief paper addresses the limitations of the current conceptual models of violent
      radicalization. Beyond understanding the path leading from radicalization of
      opinion to violent radicalization, it proposes to consider the non-violent
      outcomes of radicalization of opinions in the current social context and to study
      these outcomes in multiple settings for both minorities and majorities. Moving
      beyond the implicit linearity of current models and promoting a systemic vision
      would help to decrease the actual profiling of targeted communities and support
      the design of community-based prevention programs structured on these alternative
      outcomes, and in particular on the emergence of social solidarities in groups
      expressing discontent with the status quo.

PMID- 29356676
TI  - An exploration of citizen science for population health research in retail food
      environments.
AB  - Public engagement is an essential component of public health research, practice,
      knowledge exchange processes, and decision making. Citizen science was first
      documented in the early 1900s as an approach to public engagement and there is
      growing interest in how it can be used in health research. This commentary
      describes how citizen science approaches were incorporated into a public
      engagement activity as part of a population health intervention research project
      on the retail food environment, a workshop we hosted called The Food In This
      Place in St. John's, Newfoundland and Labrador. We used citizen science methods
      and approaches to train and support participants to critically analyze a sample
      of everyday local retail food environments.

PMID- 29356677
TI  - Caring for seniors living with dementia means caring for their caregivers too.
AB  - To improve the care of seniors living with dementia, current initiatives
      typically target better identification and treatment of the patient. Our recent
      survey, however, shows we should also focus more on the needs of the informal
      caregivers who care for this population in primary care settings. This three
      round Delphi survey sought caregivers' views on the most frequent and difficult
      decisions that seniors with dementia, their informal caregivers, and health care
      providers face in primary care settings in the province of Quebec. Respondents
      consisted of 31 health care professionals, informal caregivers, managers,
      representatives of community-based organizations devoted to these seniors, and
      clinical researchers involved in the organization of care or services to seniors
      with dementia. When we asked respondents to rank 27 common but difficult
      decisions involving benefit/harm trade-offs, 83% ranked the decision to choose an
      option to reduce the burden of informal caregivers as one of the five most
      important decisions. Choosing a treatment to manage agitation, aggression or
      psychotic symptoms followed closely, with 79% of respondents selecting it as one
      of the five most important decisions. Our results point to the importance of
      attending to the needs of informal caregivers and improving the management of
      behavioural and psychological symptoms of dementia.

PMID- 29356678
TI  - Pre-exposure prophylaxis for HIV prevention in East and Southern Africa.
AB  - Pre-exposure prophylaxis (PrEP) has proven to be highly effective in preventing
      HIV in uninfected persons when properly adhered to. East and Southern African
      countries that suffer from high HIV prevalence and incidence are increasingly
      adopting PrEP as an HIV prevention strategy for their high-risk populations,
      including for young women. Structural factors such as poverty, lack of education,
      and gender-based violence may compromise their PrEP uptake and adherence,
      however. Choice-disabled young women are most at risk of HIV infection and least
      able to apply HIV prevention choices. For successful rollout of this biomedical
      solution, we need structural interventions that address these underlying drivers
      of the HIV epidemic.

PMID- 29356679
TI  - Authors' response to Invited Commentary by Brady and Beausoleil.

PMID- 29356680
TI  - Cannabis education: Prevalence and socio-demographic correlates among Ontario
      middle and high school students.

PMID- 29356681
TI  - Erratum.

PMID- 29356682
TI  - Targeting LSD2 in breast cancer.

PMID- 29356683
TI  - SLPI: a new target for stopping metastasis.

PMID- 29356684
TI  - Epithelial plasticity in cancer: beyond metastasis.

PMID- 29356685
TI  - The stromal fibrosis in aging ovary.

PMID- 29356687
TI  - Obesity and inflammatory bowel disease: diagnostic and therapeutic implications.
AB  - PURPOSE OF REVIEW: The review summarizes our current understanding of how obesity
      impacts diagnostic studies and therapies used in inflammatory bowel disease (IBD)
      as well as the safety and efficacy of medical and surgical weight loss therapies
      in the obese IBD patient. RECENT FINDINGS: Many of the diagnostic tools we rely
      on in the identification and monitoring of IBD can be altered by obesity. Obesity
      is associated with increased acute phase proteins and fecal calprotectin. It can
      be more difficult to obtain and interpret cross sectional imaging of obese
      patients. Recent studies have also shown that common therapies used to treat IBD
      may be less effective in the obese population and may impact comorbid disease.
      Our understanding of how best to measure obesity is evolving. In addition to BMI,
      studies now include measures of visceral adiposity and subcutaneous to visceral
      adiposity ratios. An emerging area of interest is the safety and efficacy of
      obesity treatment including bariatric surgery in patients with IBD. A remaining
      question is how weight loss may alter the course of IBD. SUMMARY: The proportion
      of obese IBD patients is on the rise. Caring for this population requires a
      better understanding of how obesity impacts diagnostic testing and therapeutic
      strategies. The approach to weight loss in this population is complex and future
      studies are needed to determine the safety of medical or surgical weight loss and
      its impact on the course of disease.

PMID- 29356686
TI  - Predictors of gait speed and its change over three years in community-dwelling
      older people.
AB  - We aimed to assess whether and how changes in brain volume and increases in white
      matter hyperintensity (WMH) volume over three years predict gait speed and its
      change independently of demographics, vascular risk factors and physical status.
      We analyzed 443 individuals from the Lothian Birth Cohort 1936, at mean age 73
      and 76 years. Gait speed at age 76 was predicted by age, grip strength and body
      mass index at mean age 73, three-year brain volume decrease and WMH volume
      increase, explaining 26.1% of variance. Decline in gait speed to age 76 was
      predicted by the same five variables explaining 40.9% of variance. In both
      analyses, grip strength and body mass index explained the most variance. A
      clinically significant decline in gait speed (>= 0.1 m/s per year) occurred in
      24.4%. These individuals had more structural brain changes. Brain volume and WMH
      changes were independent predictors of gait dysfunction and its three-year
      change, but the impact of malleable physical factors such as grip strength or
      body mass index was greater.

PMID- 29356689
TI  - The impact of myeloperoxidase on HDL function in myocardial infarction.
AB  - PURPOSE OF REVIEW: The focus in cardiovascular research is shifting from
      determining mass HDL cholesterol levels toward investigating HDL functionalities
      as biomarker for cardiovascular disease. Myeloperoxidase (MPO), a main effector
      enzyme of the innate immune system, is increasingly implicated to negatively
      impact HDL function by various chemical modifications of HDL-associated proteins.
      This review summarizes recent insights how MPO affects HDL function in the
      setting of acute myocardial infarction (MI), mainly focusing on human data.
      RECENT FINDINGS: First the mechanisms how MPO renders HDL particles dysfunctional
      and the usefulness of MPO as prospective biomarker for MI incidence and outcomes
      are described. Then the evidence for MPO causing specific HDL function
      impairments in MI and the clinical value of these observations is discussed in
      the context of the different HDL function assays employed. SUMMARY: MPO
      modification of HDL in acute MI generates dysfunctional HDL. Features of HDL
      dysfunction can be used to stratify MI patients and seem associated with
      outcomes. More prospective studies are warranted to explore, if MPO-modified HDL
      is causally linked to severity and outcomes of MI. If this could be established,
      MPO would represent an attractive target to improve HDL dysfunction in MI and
      provide clinical benefit for patients.

PMID- 29356688
TI  - Diabetes pathogenic mechanisms and potential new therapies based upon a novel
      target called TXNIP.
AB  - PURPOSE OF REVIEW: Thioredoxin-interacting protein has emerged as a major factor
      regulating pancreatic beta-cell dysfunction and death, key processes in the
      pathogenesis of type 1 and type 2 diabetes. Accumulating evidence based on basic,
      preclinical, and retrospective epidemiological research suggests that TXNIP
      represents a promising therapeutic target for diabetes. The present review is
      aimed at providing an update regarding these developments. RECENT FINDINGS: TXNIP
      has been shown to be induced by glucose and increased in diabetes and to promote
      beta-cell apoptosis, whereas TXNIP deletion protected against diabetes. More
      recently, TXNIP inhibition has also been found to promote insulin production and
      glucagon-like peptide 1 signaling via regulation of a microRNA. beta-Cell TXNIP
      expression itself was found to be regulated by hypoglycemic agents, carbohydrate
      response-element-binding protein, and cytosolic calcium or the calcium channel
      blocker, verapamil. Retrospective studies now further suggest that verapamil use
      might be associated with a lower incidence of type 2 diabetes in humans. SUMMARY:
      TXNIP has emerged as a key factor in the regulation of functional beta-cell mass
      and TXNIP inhibition has shown beneficial effects in a variety of studies. Thus,
      the inhibition of TXNIP may provide a novel approach to the treatment of
      diabetes.

PMID- 29356690
TI  - Bacterial Biofilms on Extracorporeal Membrane Oxygenation Catheters.
AB  - Despite the advantages of extracorporeal membrane oxygenation (ECMO), secondary
      catheter infection remains a major concern during ECMO support. In this study, to
      clarify the mechanism of ECMO catheter-related infection, we evaluated the impact
      of infection on biofilm formation on the surfaces of ECMO catheters, and we
      investigated clinical factors associated with biofilm formation. Catheters used
      for ECMO were prospectively collected aseptically from the femoral vein, internal
      jugular vein, and femoral artery of 81 patients with acute cardiorespiratory
      failure between January 2015 and October 2016. Prepared catheter sections were
      investigated by fluorescence microscopy, confocal scanning laser microscopy,
      transmission electron microscopy, and using semiquantitative culture methods. Of
      the 81 patients, 51 were assigned to the infection group and 30 to a control
      group. Biofilms were identified in 43.1% patients in the infection group, and in
      20% controls (p = 0.034). Extracorporeal membrane oxygenation flow, systemic
      infection, and carbapenem-resistant Acinetobacter baumannii (CRAB) infection were
      associated with biofilm formation in a univariate analysis (odds ratio [OR]:
      1.00, 95% confidence interval [CI]: 1.00-1.00, p = 0.007; OR: 3.03, 95% CI: 1.06
      8.69, p = 0.039; OR: 9.60, 95% CI: 2.94-31.30, p < 0.001, respectively). However,
      of these factors, only CRAB infection was found to independently predict the
      presence of a biofilm by a multivariate logistic regression analysis (OR: 9.60,
      95% CI: 2.94-31.30; p < 0.001). Biofilms were more prevalent in patients with an
      infection than in uninfected controls. Carbapenem-resistant A. baumannii
      infection was identified as an independent risk factor for biofilm formation on
      ECMO catheters.

PMID- 29356691
TI  - The epileptic encephalopathy jungle - from Dr West to the concepts of aetiology
      related and developmental encephalopathies.
AB  - PURPOSE OF REVIEW: We aim to further disentangle the jungle of terminology of
      epileptic encephalopathy and provide some insights into the current understanding
      about the aetiology and pathophysiology of this process. We cover also the key
      features of epilepsy syndromes of infancy and childhood which are considered at
      high risk of developing an epileptic encephalopathy. RECENT FINDINGS: The concept
      of 'epileptic encephalopathy' has progressively been elaborated by the
      International League Against Epilepsy according to growing clinical and
      laboratory evidence. It defines a process of neurological impairment caused by
      the epileptic activity itself and, therefore, potentially reversible with
      successful treatment, although to a variable extent. Epileptic activity
      interfering with neurogenesis, synaptogenesis, and normal network organization as
      well as triggering neuroinflammation are among the possible pathophysiological
      mechanisms leading to the neurological compromise. This differs from the newly
      introduced concept of 'developmental encephalopathy' which applies to where the
      epilepsy and developmental delay are both because of the underlying aetiology and
      aggressive antiepileptic treatment may not be helpful. SUMMARY: The understanding
      and use of correct terminology is crucial in clinical practice enabling
      appropriate expectations of antiepileptic treatment. Further research is needed
      to elucidate underlying pathophysiological mechanisms, define clear outcome
      predictors, and find new treatment targets.

PMID- 29356692
TI  - Antitumor effects of histone deacetylase inhibitor suberoylanilide hydroxamic
      acid in epidermal growth factor receptor-mutant non-small-cell lung cancer lines
      in vitro and in vivo.
AB  - Histone acetylation is one of the most abundant post-translational modifications
      in eukaryotic cells; aberrant histone acetylation is related to a range of cancer
      types because of the dysregulation of histone deacetylases (HDACs). Inhibition of
      HDACs leads to suppression of tumor growth in multiple cancers, whereas the
      inhibitory effects of HDAC inhibitors remain incompletely understood in epidermal
      growth factor receptor (EGFR)-mutant lung cancers. In this study, the antitumor
      effects of HDACs inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat)
      were examined in EGFR-mutant lung cancer cell lines. The results of the present
      work showed that SAHA markedly inhibited cell viability and proliferation,
      induced cell apoptosis by arresting the cell cycle in the G2/M phase, and
      significantly reduced tumor growth in a xenograft model. Further study confirmed
      that the suppression function of SAHA might be mediated by regulating the ERK
      dependent and/or the AKT-dependent pathway; meanwhile, angiogenesis abrogation
      induced by SAHA exerted effects on tumor regression in vivo. Taken together, our
      results identify the antitumor effects of HDACs inhibitor SAHA as an alternative
      therapeutic application for the epigenetic treatment of EGFR-mutant non-small
      cell lung cancer.

PMID- 29356694
TI  - The optimal duration of treatment for skin and soft tissue infections and acute
      bacterial skin and skin structure infections.
AB  - PURPOSE OF REVIEW: To summarize the current finding on SSTIs/ABSSSIs treatment
      duration. RECENT FINDINGS: In 2013, the FDA approved the definition of acute
      bacterial skin and skin structure infections (ABSSSIs). From a clinical point of
      view, the new definition may present some advantages: the definition of the
      severity of the disease, the measurement of reduction in lesion size, and
      effectiveness of treatment primary endpoint at 48-72 h after treatment
      initiation. New therapeutic options with improved efficacy, safety, and/or
      pharmacodynamics are available for ABSSSIs and so far, several questions still
      need to be addressed for the management of these infections, including treatment
      duration. SUMMARY: There is a wide variation of duration of antimicrobial
      treatment in skin and soft tissue infections. Plenty of published data available
      suggest that we should focus on the early response to shorten duration of
      treatment, and that the antimicrobial stewardship perspective is extremely
      helpful in underscoring the need for composite outcomes in clinical practice, as
      multiple tools are available to increase cost-efficacy, including reduction of
      treatment changes, early oral switch, early discharge (even from the Emergency
      Department), outpatient antimicrobial treatment, long-acting antibiotics, and all
      together, de-escalation treatment strategies.

PMID- 29356693
TI  - Sonic hedgehog and Wnt/beta-catenin pathways mediate curcumin inhibition of
      breast cancer stem cells.
AB  - Cancer stem cells (CSCs) play an essential role in the progression of many
      tumors. Sonic hedgehog (Shh) and Wnt/beta-catenin pathways are crucial in
      maintaining the stemness of CSCs. Curcumin has been shown to possess anticancer
      activity. However, the interventional effect of curcumin on breast CSCs has not
      been elucidated. In the present study, we investigated the role of Shh and
      Wnt/beta-catenin pathway in curcumin inhibition of breast CSCs. We showed that
      the levels of breast CSCs markers were significantly elevated in SUM159 and MCF7
      sphere-forming cells. We further illustrated that curcumin effectively decreased
      breast CSCs activity by inhibiting tumor sphere formation, decreasing breast CSCs
      markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and
      inducing apoptosis. Moreover, we showed that downregulation of Shh and Wnt/beta
      catenin activity resulted in breast CSCs inhibition; curcumin exerted an
      inhibitory effect on breast CSCs by suppressing both Shh and Wnt/beta-catenin
      pathways. Taken together, these results indicated curcumin inhibition of breast
      CSCs by downregulation of Shh and Wnt/beta-catenin pathways. Findings from this
      study could provide new insights into the potential therapeutic application of
      curcumin in breast CSCs elimination and cancer intervention.

PMID- 29356695
TI  - Using polyphenol derivatives to prevent muscle wasting.
AB  - PURPOSE OF REVIEW: To highlight recent evidence for the ability of polyphenols
      and their derivatives to reduce muscle wasting in different pathological states.
      RECENT FINDINGS: From January 2016 to August 2017, four articles dealt with the
      effects of polyphenols on muscle wasting, which were all carried out in mice. The
      four studies found that polyphenols reduced muscle mass loss associated with
      cancer cachexia, acute inflammation or sciatic nerve section. One study even
      showed that muscle mass was totally preserved when rutin was added to the diet of
      mice undergoing cancer cachexia. The beneficial effects of polyphenols on muscle
      wasting were mainly due to a reduction in the activation of the nuclear factor
      kappa B pathway, a lower oxidative stress level and a better mitochondrial
      function. In addition, urolithin B was found to have a testosterone-like effect
      and to favorably regulate muscle protein balance. SUMMARY: During the last 20
      months, additional data have been collected about the beneficial effects of
      rutin, curcumin, quercetin, ellagitanins and urolithin B to limit the loss of
      muscle mass associated with several pathological states. However, currently,
      scientific evidence lacks for their use as nutraceuticals in human.

PMID- 29356696
TI  - Parenteral nutrition in intensive care patients: medicoeconomic aspects.
AB  - PURPOSE OF REVIEW: Parenteral nutrition (PN) alone or as supplemental parenteral
      nutrition (SPN) has been shown to prevent negative cumulative energy balance, to
      improve protein delivery and, in some studies, to reduce infectious morbidity in
      ICU patients who fail to cover their needs with enteral nutrition (EN) alone.
      RECENT FINDINGS: The optimization of energy provision to an individualized energy
      target using either early PN or SPN within 3-4 days after admission has recently
      been reported to be a cost-saving strategy mediated by a reduction of infectious
      complications in selected intensive care patients. SUMMARY: EN alone is often
      insufficient, or occasionally contraindicated, in critically ill patients and
      results in growing energy and protein deficit. The cost benefit of using early PN
      in patients with short-term relative contraindications to EN has been reported.
      In selected patients SPN has been associated with a decreased risk of infection,
      a reduced duration of mechanical ventilation, a shorter stay in the ICU.
      Altogether four studies have investigated the costs associated with these
      interventions since 2012: two of them from Australia and Switzerland have shown
      that optimization of energy provision using SPN results in cost reduction,
      conflicting with other studies. The latter encouraging findings require further
      validation.

PMID- 29356697
TI  - What is the optimal target for treat-to-target strategies in rheumatoid
      arthritis?
AB  - PURPOSE OF REVIEW: There has been a trend over time to aim for stricter treatment
      targets in the treatment of rheumatoid arthritis (RA). We reviewed recent
      literature to attempt to identify the optimal target in treat-to-target
      strategies in RA. RECENT FINDINGS: Achieving lower disease activity was shown to
      be beneficial, but few studies directly compared the effect of aiming for
      different treatment targets. Based on the limited available evidence, aiming for
      remission seems to result in more patients achieving (drug-free) remission than
      aiming for low disease activity (LDA), but it does not seem to result in better
      physical functioning. There are indications that adherence to a remission
      targeted protocol can be lower. In randomized trials in which LDA or remission
      were compared with ultrasound remission targets, treatment targeted at ultrasound
      remission was associated with more intensive treatment, but it did not result in
      better clinical or imaging outcomes. SUMMARY: There were no benefits of aiming
      for ultrasound remission in RA-patients. To decide whether remission or LDA is
      the best target in the treatment of RA-patients, a randomized clinical trial
      comparing both targets would be needed. On an individual level, cotargets such as
      functional ability should be considered.

PMID- 29356699
TI  - A novel compound heterozygous mutations in protein C gene causing neonatal
      purpura fulminans.
AB  - : Neonatal purpura fulminans is a rare, life-threatening disease caused by severe
      congenital deficiency of protein C (PC) because of homozygous or compound
      heterozygous mutations in the PROC gene. Mutation analysis plays a critical role
      in diagnosing the disorder and offering prenatal guidance. In this study, we
      identified a genetic defect in the PROC gene leading to neonatal purpura
      fulminans. The propositus had very low PC activity (4%) and PC antigen activity
      (5%). DNA screening of the whole PROC gene revealed two compound heterozygous
      mutations in exon8 (c.795_796insA) and exon9 (c.1206_1207insG). These two
      variations led to the compound heterozygous mutations of Gly266Argfs4 and
      Pro405Alafs20, which were inherited from the patient's father and mother,
      respectively. His older sister is heterozygous for the Gly266Argfs4 mutation. The
      inserted nucleotides alter the protein by introducing a stop codon at the
      subsequent AA position, resulting in a truncated protein compared with the wild
      type. We deduced that the compound heterozygous mutations are responsible for the
      PC deficiency, the Gly266Argfs4 mutation has been confirmed to be a novel
      mutation.

PMID- 29356698
TI  - Development of encorafenib for BRAF-mutated advanced melanoma.
AB  - PURPOSE OF REVIEW: To describe the pharmacological properties, preclinical and
      clinical data of the novel V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF)
      inhibitor encorafenib (LGX818) and to compare these with established BRAF
      inhibitors in the treatment of locally advanced or metastatic melanoma. RECENT
      FINDINGS: Encorafenib has shown improved efficacy in the treatment of metastatic
      melanoma in comparison with vemurafenib. Combination with the MEK inhibitor
      (MEKi) binimetinib allows for higher dose intensities of encorafenib further
      improving response rates (RRs). SUMMARY: Combination therapy with BRAF and MEKi
      has evolved as a standard of care in the treatment of locally advanced or
      metastatic BRAF-mutated melanoma. Despite compelling initial RRs, development of
      treatment resistance eventually leads to tumor progression in the majority of
      BRAF/MEK-inhibitor treated patients. Moreover, treatment-related adverse events
      are frequent, resulting in a substantial proportion of dose modifications and/or
      treatment discontinuations. The second-generation BRAF inhibitor encorafenib has
      been developed aiming at improved efficacy and tolerability through modifications
      in pharmacological properties. Clinical phase 3 data show improved progression
      free survival both for encorafenib monotherapy and combination therapy with
      binimetinib compared with vemurafenib. Overall survival data and regulatory
      approval of this novel substance are eagerly awaited.

PMID- 29356700
TI  - The effects of transport temperature and time on routine and specialized
      coagulation assays.
AB  - : Coagulation laboratories have largely stopped transporting whole blood
      specimens on ice, due to adverse effects on factor VIII, von Willebrand factor,
      and the prothrombin time. However, it is unknown whether ice should be required
      or avoided for other coagulation assays. Furthermore, the amount of time that
      specimens remain stable during transportation at room temperature (RT) is also
      largely unknown for many coagulation tests. Therefore, this study investigated
      specimen stability on ice and RT for a comprehensive panel of coagulation tests.
      One tube of whole blood from each volunteer (n = 22) was centrifuged immediately
      (time 0), one was stored for 4 h on ice, and one was stored for 4 h at RT before
      centrifugation. Among time 0, 4 h on ice, and 4 h at RT samples, no statistically
      significant differences were found for fibrinogen, activated protein C
      resistance, thrombin time, reptilase time, antithrombin activity, chromogenic
      protein C, factor XII, and antiplasmin activity. Prothrombin time, activated
      partial thromboplastin time, factors IX, XI, protein S activity, and plasminogen
      activity showed statistically, but not clinically, significant differences. On
      ice, the only analytes that showed clinically significant changes (>=6.0% from
      time 0) were factors VII, VIII, von Willebrand factor antigen, and ristocetin
      cofactor, which were 14.0% higher, and 19.2, 9.5, and 18.8% lower than time 0,
      respectively. At RT, all analytes were stable except factor VIII was 9.4% lower
      than time 0. Only factors II, V, X, and PTT-LA lupus anticoagulant showed a
      possible slight benefit from ice, but the statistically significant differences
      were not clinically significant. Ice did not substantially benefit any of the
      coagulation assays. All tests were stable at RT, except more study is needed
      regarding factor VIII.

PMID- 29356701
TI  - Is Surgery the Preferred Treatment for Neurologically Intact Patients With
      Unilateral Facet Fractures and a Nonsubluxated Cervical Spine?

PMID- 29356702
TI  - Environmental influences on Child Health Outcomes, a Research Program of the
      National Institutes of Health.

PMID- 29356703
TI  - Home Hearing Test: Within-Subjects Threshold Variability.
AB  - BACKGROUND: The Home Hearing Test (HHT) is an automated pure-tone threshold test
      that obtains an air conduction audiogram at five test frequencies. It was
      developed to provide increased access to hearing testing and support home
      telehealth programs. PURPOSE: Test and retest thresholds for 1000-Hz stimuli were
      analyzed to determine intrasubject variability from two independent data sets.
      RESEARCH DESIGN: Prospective, repeated measures. STUDY SAMPLE: In the Veterans
      Affairs (VA) study, results from 26 subjects 44 to 88 years of age (mean = 65)
      recruited from the Nashville VA audiology clinic were analyzed. Subjects were
      required to have a Windows PC in the home and were self-reported to be
      comfortable with using computers. Two subjects had normal hearing, and 24 had
      hearing losses of various severities and configurations. The National Center for
      Rehabilitative Auditory Research (NCRAR) sample included 100 subjects (68 males;
      32 females) with a complaint of hearing difficulty recruited from the local
      community and Veteran population. Subjects ranged in age from 32 to 87 years
      (mean = 63.7 years). They were tested in a quiet room at the NCRAR. DATA
      COLLECTION AND ANALYSIS: Subjects in the VA study were provided kits for
      installing HHT on their home computers. HHT was installed on a computer at NCRAR
      to test subjects in the NCRAR study. HHT obtains a five-frequency air conduction
      audiogram with a retest of 1000 Hz in both ears. Only the 1000-Hz test-retest
      results are analyzed in this report. Six statistical measures of test-retest
      variability are reported. RESULTS: Test and retest thresholds were highly
      correlated in both studies (r >= 0.96). Test-retest differences were within +/-5
      dB >=92% of the time in the two studies. Standard deviations of absolute test
      retest difference were <=3.5 dB in the two studies. CONCLUSIONS: Intrasubject
      variability is comparable to that obtained with manual testing by audiologists in
      sound-treated test rooms.

PMID- 29356704
TI  - Familial hypercholesterolemia: experience from the French-Canadian population.
AB  - PURPOSE OF REVIEW: There has recently been renewed interest in the study of the
      various facets of familial hypercholesterolemia, a severe monogenic disease
      associated with elevated LDL-cholesterol and premature cardiovascular disease
      (CVD). In the present review, novel data presenting the frequency of familial
      hypercholesterolemia as well as factors modulating the cardiovascular risk in
      familial hypercholesterolemia will be discussed. RECENT FINDINGS: Recent studies
      have showed that familial hypercholesterolemia is much more prevalent than
      initially thought. Classically, it was estimated that familial
      hypercholesterolemia affected one in 500 people worldwide, but a recent large
      scale meta-analysis has shown a prevalence closer to one in 250. In the French
      Canadian population, this disease is even more frequent reaching one in 81 in
      certain regions of the Province of Quebec. Several novel studies in the French
      Canadian population have shown that the clinical outcomes in familial
      hypercholesterolemia seem to be greatly influenced by risk factors other than LDL
      cholesterol. Also, scores to predict CVD in familial hypercholesterolemia have
      been recently proposed. SUMMARY: Familial hypercholesterolemia is more frequent
      than initially thought and the phenotype of this disease can be variable. Indeed,
      both clinical and genetic variables can modulate the CVD risk in this population.

PMID- 29356705
TI  - Genetics of familial hypercholesterolemia: a tool for development of novel lipid
      lowering pharmaceuticals?
AB  - PURPOSE OF REVIEW: Familial hypercholesterolemia is characterized by high LDL
      cholesterol and an elevated risk to develop coronary heart disease. Mutations in
      LDL receptor-mediated cholesterol uptake are the main cause of familial
      hypercholesterolemia. However, multiple mutations in various other genes are also
      associated with high LDL cholesterol and even familial hypercholesterolemia.
      Thus, pharmaceuticals that target these genes and proteins might be attractive
      treatment options to reduce LDL cholesterol. This review provides an overview of
      the recent developments and clinical testing of such pharmaceuticals. RECENT
      FINDINGS: About 80 genes are associated with hypercholesterolemia but only
      pharmaceuticals that inhibit cholesteryl ester transfer protein (CETP),
      angiopoietin-related protein 3 (ANGPTL3), and apolipoprotein C-III (apoC-III)
      have recently been tested in clinical trials. Inhibition of CETP and ANGPTL3
      lowered LDL cholesterol. ANGPTL3 inhibition had the largest effect and was even
      effective in familial hypercholesterolemia patients. The effect of apoC-III
      inhibition on LDL cholesterol is not conclusive. SUMMARY: Of the many potential
      pharmaceutical targets involved in LDL cholesterol, only a few have been studied
      so far. Of these, pharmaceuticals that inhibit CETP or ANGPTL3 are promising
      novel treatment options to reduce LDL cholesterol but the effect of apoC-III
      inhibition requires more research.

PMID- 29356706
TI  - Traumatic Obturator Dislocation Following Total Hip Arthroplasty Managed with
      Closed Reduction: A Case Report and Review of the Literature.
AB  - CASE: A 30-year-old man sustained an obturator dislocation of a left total hip
      prosthesis with a concomitant ipsilateral fracture of the greater trochanter
      following a high-energy motor-vehicle accident. With the patient under general
      anesthesia, the hip was successfully treated with closed reduction, as confirmed
      with intraoperative fluoroscopy and postoperative radiographs. Postreduction, the
      patient was able to mobilize with abduction restrictions and had no additional
      instability. Short-term follow-up showed evidence of healing of the greater
      trochanter. CONCLUSION: Obturator dislocation of a total hip prosthesis is an
      exceedingly rare injury. Closed reduction can be considered as a treatment option
      in the appropriate patient, with a satisfactory short-term outcome.

PMID- 29356707
TI  - Outcomes of simultaneous liver-kidney transplantation: implications for patient
      selection.
AB  - PURPOSE OF REVIEW: Rates of simultaneous liver kidney (SLK) transplantation have
      continued to increase despite lack of clear allocation guidelines and outcomes
      data. The organ procurement and transplantation network (OPTN)/UNOS board
      approved a new SLK allocation policy to standardize medical eligibility and
      optimize organ utilization. This review highlights the rationale behind these new
      selection criteria and posttransplant outcomes in various patient populations.
      RECENT FINDINGS: Uniform criteria for SLK transplantation were adopted in August
      2017 and state SLK should be reserved for select patients with cirrhosis who have
      chronic kidney disease for longer than 3 months, sustained acute kidney injury,
      or particular metabolic diseases. Many patients who previously underwent SLK did
      not meet these criteria, reducing organ availability for patients awaiting kidney
      alone transplantation. The new criteria includes a 'safety net' policy allowing
      for renal transplant priority for liver-alone recipients who do not meet criteria
      for SLK but fail to have renal recovery within the first year. SUMMARY: The new
      SLK allocation policy was adopted to avoid kidney transplantation in those
      patients who have a significant chance of recovering renal function post-liver
      transplant and those with a poor chance of survival in whom SLK is futile.

PMID- 29356708
TI  - Nonalcoholic steatohepatitis: the new frontier for liver transplantation.
AB  - PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is a growing cause of
      chronic liver disease globally and nonalcoholic steatohepatitis is projected to
      become the most common indication for liver transplantation. The purpose of this
      review is to highlight key issues surrounding NAFLD as an indication for liver
      transplantation, including its increasing prevalence, outcomes related to liver
      transplantation, development of post liver transplant NAFLD and NAFLD in the
      liver donor pool. RECENT FINDINGS: With the advent of direct-acting antiviral
      therapies, the proportion of patients on the liver transplant list or undergoing
      liver transplant for chronic hepatitis C infection is steadily decreasing. In
      contrast, the number transplants performed for NAFLD is increasing. By 2030, it
      is estimated that the incidence of decompensated cirrhosis and hepatocellular
      carcinoma will increase by 168 and 137%, respectively, and the number of deaths
      will increase by 178%. SUMMARY: Liver transplantation cures cirrhosis but does
      not treat the underlying metabolic disease associated with NAFLD. Thus,
      strategies to control comorbidities in patients with NAFLD prior to transplant
      are needed to decrease waitlist mortality and the recurrence of NAFLD after liver
      transplant. NAFLD in the donor pool is also a growing concern. Strategies to
      minimize steatosis and expand the number of donors are critical to meet the
      growing demand for liver transplantation.

PMID- 29356709
TI  - Copy number variations and fetal ventriculomegaly.
AB  - PURPOSE OF REVIEW: Ventriculomegaly is one of the most common abnormal
      sonographic findings, which is associated with congenital infection, chromosomal
      and additional structural abnormalities. Currently, karyotype analysis is the
      primary method to detect chromosomal abnormalities in fetuses with
      ventriculomegaly. Recently, with the introduction of chromosomal microarray
      analysis (CMA) in prenatal diagnosis, copy number variations (CNVs) have been
      identified in cases of ventriculomegaly. The purpose of this review is to
      summarize the current knowledge about the genetic cause of fetal
      ventriculomegaly, with particular attention to primary articles regarding the
      association between CNVs and fetal ventriculomegaly. RECENT FINDINGS: Recent
      studies have disclosed that in addition to numerical chromosomal abnormalities
      and large chromosomal imbalances, pathogenic CNVs are another important genetic
      cause of fetal ventriculomegaly, which may be involved in the pathological
      process of fetal ventriculomegaly as well as postnatal neurodevelopmental
      disorders. Furthermore, it is reported that the incidences of pathogenic CNVs in
      fetuses with ventriculomegaly were associated with the presence of other
      structural anomalies, but were irrelevant to the severity of ventriculomegaly.
      SUMMARY: CNVs are an important cause of fetal ventriculomegaly and CMA should be
      offered to all fetuses with ventriculomegaly, regardless of the degree of
      ventriculomegaly or whether combined with other structural anomalies.

PMID- 29356710
TI  - Functional Trajectories Before and After Major Surgery in Older Adults.
AB  - OBJECTIVES: We hypothesized that distinct sets of functional trajectories can be
      identified in the year before and after major surgery, with unique transition
      probabilities from pre to postsurgical functional trajectories, and that outcomes
      would be better among participants undergoing elective versus nonelective
      surgery. BACKGROUND: Major surgery is common and can be highly morbid in older
      persons. The relationship between the course of disability (ie, functional
      trajectory) before and after surgery in older adults has not been well-studied
      for most operations. METHODS: Prospective cohort study of 754 community-living
      persons 70 years or older. The analytic sample included 250 participants who
      underwent their first major surgery during the study period. RESULTS: Before
      surgery, 4 functional trajectories were identified: no disability (n = 60,
      24.0%), and mild (n = 84, 33.6%), moderate (n = 73, 29.2%), and severe (n = 33,
      13.2%) disability. After surgery, 4 functional trajectories were identified:
      rapid (n = 39, 15.6%), gradual (n = 76, 30.4%), partial (n = 70, 28.0%), and
      little (n = 57, 22.8%) improvement. Rapid improvement was seen for n = 31 (51.7%)
      participants with no disability before surgery, but was uncommon among those with
      mild disability (n = 8, 9.5%) and was not observed in the moderate and severe
      trajectory groups. For participants with mild to moderate disability before
      surgery, gradual improvement (n = 46, 54.8%) and partial improvement (n = 36,
      49.3%) were most common. Most participants with severe disability (n = 27, 81.8%)
      before surgery exhibited little improvement. Outcomes were better for
      participants undergoing elective versus nonelective surgery. CONCLUSIONS:
      Functional prognosis in the year after major surgery is highly dependent on
      premorbid function.

PMID- 29356711
TI  - Effect of mineralocorticoid antagonists on blood pressure lowering: overview and
      meta-analysis of randomized controlled trials in hypertension.
AB  - OBJECTIVES: Although mineralocorticoid antagonists (MRAs) have been proposed as
      effective fourth-line blood pressure (BP)-lowering agents in resistant
      hypertension, this effect in hypertension at-large is unclear. We evaluated
      whether MRAs-mediated BP lowering is both effective and safe against controls and
      whether the extent of BP lowering differs between resistant hypertension and
      nonresistant hypertension . METHODS: We searched Medline and the Cochrane
      Collaboration Library databases from 1991 to mid-September 2017 for randomized
      controlled trials (RCTs), in which MRAs were compared with placebo or other
      active drugs. Main outcomes were SBP and DBP lowering and treatment-related
      discontinuations. Continuous outcome variables were pooled as mean difference and
      the categorical variables as risk ratios, both with 95% confidence interval (CI).
      The risk of bias was assessed by using the Cochrane collaboration tool. RESULTS:
      We included 21 RCTs (2736 patients) of MRAs compared either with placebo or with
      active agents. Whenever all selected trials were analyzed together (MRAs versus
      controls), the resulting BP reduction was -7.6 (95% CI -10 to -5.3) mmHg for SBP
      and -2.5 (95% CI -4.2 to -0.8) mmHg for DBP, while limiting our analysis to MRAs
      versus placebo mean difference was increased by -2.1/-1.3 mmHg. We find no
      differential BP lowering between resistant hypertension and non-resistant
      hypertension. Treatment-related discontinuations were not different compared with
      either placebo or active comparators. CONCLUSION: As the extent of BP lowering
      following treatment with MRAs in patients with and without resistant hypertension
      was similar and not accompanied by increased rate of treatment-related
      discontinuations compared with other active comparators, these agents may have a
      role in BP lowering in already treated hypertensive patients who did not reach
      target BP values.

PMID- 29356712
TI  - Knowledge, availability, and use of ambulatory and home blood pressure monitoring
      in primary care in Spain: the MAMPA study.
AB  - OBJECTIVE: To examine the degree of knowledge and management of automated devices
      for office blood pressure measurement (AD), home blood pressure monitoring (HBPM)
      and ambulatory blood pressure monitoring (ABPM) in primary care in Spain.
      METHODS: Online self-administered survey sent between May 2016 and February 2017
      to 2221 primary-care physicians working across Spain. Clinicians were mostly
      identified through national primary-care scientific societies (20% overall
      response rate). RESULTS: Participants' mean age was 47.7 years, 55% were women,
      and 54% reported at least 20 years of primary-care practice. Among them, 47.5%
      considered ABPM the best diagnostic method for hypertension, 23% chose HBPM, and
      7.1% chose office blood pressure. Also, 78.2% had AD available at their centers
      and 49.0% had ABPM, with slight urban/rural differences. HBPM was recommended in
      daily practice for hypertension diagnosis by 67% of participants, whereas 30%
      recommended ABPM. Cost to the patients was the main reason for not using HBPM
      (42.7%) as was lack of accessibility for not using ABPM (69.8%). Lack of specific
      training was also reported as an important reason in both cases. CONCLUSION: Even
      in the possibly best primary care scenario presented by highly motivated
      physicians (respondents to a voluntary anonymous survey), enormous gaps were
      observed between current guidelines' recommendations on ABPM and HBPM use for
      confirming hypertension and the modest degree of knowledge, availability, and use
      of these technologies.

PMID- 29356713
TI  - Pathologic Staging of Endometrial Carcinomas: Selected Areas of Difficulty.
AB  - Accurate staging of cancers is an important determinant of prognosis and guides
      optimal patient treatment. Although the International Collaboration on Cancer
      Reporting recommends that endometrial cancers (including carcinosarcomas) are
      pathologically staged using the International Federation of Gynecology and
      Obstetrics (FIGO) 2009 system, in many areas TNM [American Joint Committee on
      Cancer (AJCC) or Union for International Cancer Control (UICC)] staging is used
      or even mandated; these latter systems are based on FIGO 2009. In this review,
      areas of difficulty in the pathologic staging of endometrial carcinomas are
      covered with practical advice for the reporting pathologist. These include issues
      regarding the assessment of the depth of myometrial involvement (which may be
      rendered difficult due to a variety of factors), tumor involvement of
      adenomyosis, and assessment of cervical and uterine serosal involvement. Although
      not included in the FIGO staging system, the issue of lymphovascular space
      invasion (LVSI) is covered as this is of prognostic importance and there are
      multiple problems in the pathologic assessment of this. One important point is
      that tumors should not be upstaged based on the presence of LVSI alone without
      tissue involvement; for example, the presence of LVSI in the outer half of the
      myometrium or in cervical or adnexal vessels in a carcinoma with myoinvasion
      confined to the inner half of the myometrium is still FIGO stage IA. The issue of
      simultaneously occurring tumors of the endometrium and adnexa is also covered
      with advice on how to distinguish between synchronous independent and metastatic
      neoplasms of both endometrioid and nonendometrioid types. Recent molecular
      evidence showing that simultaneously occurring endometrioid carcinomas of the
      endometrium and ovary are clonal and thus probably represent metastatic disease
      from the endometrium to the ovary rather than synchronous independent neoplasms,
      as is widely assumed, is discussed.

PMID- 29356714
TI  - Disclosure of Harmful Medical Error to Patients: A Review With Recommendations
      for Pathologists.
AB  - Harmful error is an infrequent but serious challenge in the pathology laboratory.
      Regulatory bodies and advocacy groups have mandated and encouraged disclosure of
      error to patients. Many pathologists are interested in participating in
      disclosure of harmful error but are ill-equipped to do so. This review of the
      literature with recommendations examines the current state of the patient safety
      movement and error disclosure as it pertains to pathology and provides a
      practical and explicit guide for pathologists for who, when, and how to disclose
      harmful pathology error to patients. The authors provide a definition of harmful
      pathology error, and the rationale and principles behind effective disclosure are
      discussed. The changing culture of medicine and its effect on pathology is
      examined including the trend towards increasing transparency and patient
      engagement. Related topics are addressed including the management of expected
      adverse events, barriers to disclosure, and additional resources for the
      implementation of disclosure programs in pathology.

PMID- 29356715
TI  - Postoperative Inflammation After Endoscopic Cyclophotocoagulation: Racial
      Distribution and Effect on Outcomes.
AB  - PURPOSE: To assess the prevalence of postoperative anterior chamber reaction or
      persistent anterior uveitis (PAU) by race and its effect on intraocular pressure
      (IOP) and visual acuity (VA) after combined phacoemulsification and endoscopic
      cyclophotocoagulation (ECP) in primary open-angle glaucoma. PATIENTS AND METHODS:
      A retrospective analysis of all patients with primary open-angle glaucoma who
      underwent combined phacoemulsification cataract extraction with ECP from January
      1, 2007 to October 31, 2015. VA, IOP, presence of anterior chamber cells, steroid
      treatment, and number of IOP lowering drops were analyzed preoperatively and up
      to 3 months postoperatively. Patients were categorized according to self-reported
      race. PAU was treated according to severity and presence of symptoms. RESULTS:
      Two hundred twenty-three eyes met the inclusion criteria. PAU was present in
      22.4% of eyes. PAU was significantly correlated with race, particularly African
      American race. PAU was also associated with a lack of improvement in inflammation
      at week 1 compared with day 1 postoperatively. However, there was no significant
      difference in VA, IOP, or reduction of IOP lowering drops in those with or
      without PAU. When comparing African Americans to whites, PAU and its treatment
      were not associated with a difference in IOP reduction at 3 months. CONCLUSIONS:
      PAU is common after combined phacoemulsification and ECP and is significantly
      correlated with race. Although PAU may require prolonged postoperative treatment,
      our data does not support poorer VA or IOP outcomes.

PMID- 29356716
TI  - Chronic Hematic Cyst of the Right Maxillary Sinus and Orbit Presenting as
      Proptosis.
AB  - A 28-year-old man presented to the emergency room complaining of right proptosis.
      He also manifested eye pain and facial fullness and redness in this side. Seven
      years ago, he had right hemifacial gunshot trauma treated with surgical
      reconstruction. The CT scan showed expansion of the right maxillary sinus due to
      a hypodense nonenhancing lesion extending to the nasal cavity, masticatory space,
      and extraconal space of the orbit. MRI was performed showing high signal
      intensity of the lesion on T2-weighted images indicating a cystic nature. T1
      weighted images also demonstrated high signal intensity of the lesion suggesting
      hemorrhage. At endoscopic maxillary antrostomy, the diagnosis of a chronic
      hematic cyst was confirmed. Chronic hematic cysts of the orbit should be included
      in the differential diagnosis of proptosis, especially if there is clinical
      history of past trauma. Due to the fact that physical examination is nonspecific,
      radiologic evaluation is useful to confirm the diagnosis and for presurgical
      planning.

PMID- 29356717
TI  - Retrospective Analysis of Physician-based Surveys Published in OPRS.
AB  - PURPOSE: To review physician-based clinical surveys published in Ophthalmic
      Plastic and Reconstructive Surgery. METHODS: Complementary Ovid and PubMed
      searches of Ophthalmic Plastic and Reconstructive Surgery journal content were
      performed for the term "survey." Results were narrowed to studies that
      specifically addressed physicians' clinical practices. This search resulted in
      162 articles, and after dual-investigator independent screening, 13 surveys met
      inclusion criteria. RESULTS: Of the 13 surveys published from 2007 to January
      2017, 6 were published since 2015, showing an increased trend in survey-based
      publications. Topics included assessing practice patterns regarding eyelid
      disorders, thyroid eye disease, optic nerve sheath fenestration, anophthalmic
      socket, and diagnosing lacrimal disorders. Average response rate was 38.7% (range
      17.5-60%), with 201 average number of replies (range 72-310). Nine out of 13
      surveys included some form of statistical analysis with the remainder presenting
      data in percentages. CONCLUSIONS: There has been an increased rate of survey-type
      publications in Ophthalmic Plastic and Reconstructive Surgery over the past 10
      years. The low response rate and frequent lack of statistical analysis raise
      concerns regarding the validity and usefulness of such studies. The authors
      believe that survey studies can be improved through better standardization and
      the use of author guidelines. They have made specific recommendations to improve
      the impact of survey papers in the future.

PMID- 29356718
TI  - Suture Fixation Using Polyblend Polyethylene Sutures With Hydroxyapatite Block
      for an Intra-articular Depression Fracture of the Pisiform Bone.
AB  - Few cases in which open reduction and internal fixation was performed for
      displaced pisiform fractures have been reported. We present a new surgical
      technique for the treatment of depressed intra-articular pisiform fractures.
      First, the depressed fragment was reduced by pushing the bone tamp. Then, the
      fracture void resulting from the reduction of the depressed fragment was filled
      with a shaped hydroxyapatite block. Finally, the fragments were sutured using
      braided polyblend polyethylene sutures. The postoperative radiography could
      achieve a well-reduced articular facet, and this procedure had a good clinical
      outcome.

PMID- 29356719
TI  - Transfer of a Radial Nerve Branch to the Brachialis Nerve for Restoration of
      Elbow Flexion.
AB  - Nerve transfers for brachial plexus reconstruction and the treatment of
      peripheral nerve injury have demonstrated excellent clinical outcomes and may be
      superior to nerve grafting. Previously described nerve transfers for restoration
      of elbow flexion include the Oberlin (ulnar to musculocutaneous) and double
      fasicular (median to biceps and ulnar to brachialis) transfers. However, these
      transfers cannot be performed in patients with loss of elbow flexion and
      concomitant high median and ulnar nerve injury. Other transfers utilizing the
      thoracodorsal or intercostal nerves have been described; however, this requires
      sacrifice of the latissimus dorsi muscle or potential nerve donors for a free,
      functioning gracilis muscle transfer. The triceps lower medial head and anconeus
      motor branch is a frequently used nerve donor with minimal morbidity. As an
      alternative for this specific patient population, we report the transfer of the
      triceps lower medial head and anconeus motor branch to the brachialis nerve as an
      option to restore elbow flexion.

PMID- 29356720
TI  - Unpacking Care Coordination Through a Multiteam System Lens: A Conceptual
      Framework and Systematic Review.
AB  - BACKGROUND: The 2016 President's Cancer Panel Connected Health report calls for
      thoroughly characterizing the team structures and processes involved in
      coordinating care for people with chronic conditions. We developed a multilevel
      care coordination framework by integrating existing frameworks from the teams and
      care coordination literatures, and used it to review evidence examining care
      coordination processes for patients with cancer, diabetes, cardiovascular
      disease, and combinations of these conditions. METHODS: We searched
      Pubmed/MedLINE, CINAHL Plus, Cochrane, PsycINFO (December 2009-June 2016), and
      references from previous reviews. Studies describing behavioral markers of
      coordination between >=2 US health care providers caring for adults with cancer,
      chronic heart disease, diabetes, or populations with a combination of these
      conditions were included. Two investigators screened 4876 records and 180 full
      text articles yielding 33 studies. One investigator abstracted data, a second
      checked abstractions for accuracy. RESULTS: Most studies identified information
      sharing or monitoring as key coordination processes. To execute these processes,
      most studies used a designated role (eg, coordinator), objects and
      representations (eg, survivorship plans), plans and rules (eg, protocols), or
      routines (eg, meetings). Few examined the integrating conditions. None
      statistically examined coordination processes or integrating conditions as
      mediators of relationships between specific coordination mechanisms and patient
      outcomes. LIMITATIONS: Restricted to United States, English-language studies;
      heterogeneity in methods and outcomes. CONCLUSIONS: Limited research unpacks
      relationships between care coordination mechanisms, coordination processes,
      integrating conditions, and patient outcomes suggested by existing theory. The
      proposed framework offers an organizer for examining behaviors and conditions
      underlying effective care coordination.

PMID- 29356721
TI  - Statewide Inferior Vena Cava Filter Placement, Complications, and Retrievals:
      Epidemiology and Recent Trends.
AB  - BACKGROUND: Public awareness of inferior vena cava (IVC) filter-related
      controversies has been elevated by the Food and Drug Administration (FDA) safety
      communication in 2010. OBJECTIVES: To examine population level trends in IVC
      filter utilization, complications, retrieval rates, and subsequent pulmonary
      embolism (PE) risk. DESIGN: A retrospective cohort study. SUBJECTS: Patients
      receiving IVC filters during 2005-2014 in New York State. MEASURES: IVC filter
      specific complications, new PE occurrences and IVC filter retrievals were
      evaluated as time-to-event data using Kaplan-Meier analysis. Estimated cumulative
      risks were obtained at various timepoints during follow-up. RESULTS: There were
      91,873 patients receiving IVC filters between 2005 and 2014 in New York State
      included in the study. The average patient age was 67 years and 46.6% were male.
      Age-adjusted rates of IVC filter placement increased from 48 cases/100,000 in
      2005 to 52 cases/100,000 in 2009, and decreased afterwards to 36 cases/100,000 in
      2014. The estimated risks of having an IVC filter-related complication and filter
      retrieval within 1 year was 1.5% [95% confidence interval (CI), 1.4%-1.6%] and
      3.5% (95% CI, 3.4%-3.6%). One-year retrieval rate was higher post-2010 when
      compared with pre-2010 years (hazard ratio, 2.70; 95% CI, 2.50-2.91). Among the
      58,176 patients who did not have PE events before or at the time of IVC filter
      placement, the estimated risk of developing subsequent PE at 1 year was 2.0% (95%
      CI, 1.9%-2.1%). CONCLUSIONS: Our findings suggest that FDA communications may be
      effective in modifying statewide clinical practices. Given the 2% observed PE
      rate following prophylactic IVC filter placement, large scale pragmatic studies
      are needed to determine contemporary safety and effectiveness of IVC filters.

PMID- 29356722
TI  - Early Noninvasive Ventilation and Nonroutine Transfusion for Acute Chest Syndrome
      in Sickle Cell Disease in Children: A Descriptive Study.
AB  - OBJECTIVES: To describe the need for transfusion and short- and long-term
      evolutions of pediatric sickle cell disease patients with acute chest syndrome
      for whom early continuous noninvasive ventilation represented first-line
      treatment. DESIGN: Single-center retrospective chart study in PICU. SETTING: A
      tertiary and quaternary referral PICU. PATIENTS: All sickle cell disease patients
      5-20 years old admitted with confirmed acute chest syndrome and not transfused in
      the previous month were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Demographic data, laboratory and radiologic findings, transfusions,
      invasive ventilation, oxygen and noninvasive ventilation settings, duration of
      opioid treatment, length of hospital stay, and severe sickle cell disease
      complications in the ensuing 2 years were extracted from medical charts. Sixty
      six acute chest syndrome in 48 patients were included. Continuous early
      noninvasive ventilation was well tolerated in 65 episodes, with positive
      expiratory pressure 4 cm H2O and pressure support 10 cm H2O (median) administered
      continuously, then discontinued during 7 days (median). No patient necessitated
      invasive ventilation or died. Twenty-three acute chest syndrome (35%) received
      transfusions; none received blood exchange. Transfused patients had more frequent
      upper lobe radiologic involvement, more severe anemia, higher reticulocyte
      counts, and higher C-reactive protein than nontransfused patients. Their
      evolution was more severe in terms of length of opioid requirement, length of
      noninvasive ventilation treatment, overall time on noninvasive ventilation, and
      length of stay. At 2-year follow-up after the acute chest syndrome episode, no
      difference was observed between the two groups. CONCLUSIONS: Early noninvasive
      ventilation combined with nonroutine transfusion is well tolerated in acute chest
      syndrome in children and may spare transfusion in some patients. Early
      recognition of patients still requiring transfusion is essential and warrants
      further studies.

PMID- 29356723
TI  - Architectural Patterns are a Relevant Morphologic Grading System for Clear Cell
      Renal Cell Carcinoma Prognosis Assessment: Comparisons With WHO/ISUP Grade and
      Integrated Staging Systems.
AB  - We developed and validated an architecture-based grading for clear cell renal
      cell carcinoma (ccRCC) in an observational retrospective cohort study including
      506 tumors (principal cohort, n=254; validation cohort, n=252). Study endpoints
      were disease-free survival (DFS) and cancer-specific survival (CSS).
      Relationships with outcome were analyzed using Harrell concordance index, time
      dependent receiver operating characteristic curve, area under curve, and Cox
      regression model. An architecture-based grading was devised on positive
      likelihood ratio (LR+) for DFS at 50 months as follows: grade 1 (LR+<0.8),
      cystic, compact, acinar, clear cell papillary RCC-like, and/or regressive
      patterns; grade 2 (1.2<=LR+<5), large nest, alveolar, papillary,
      chromophobe/oncocytic cell-like, eosinophilic hyaline globule, and/or
      intratumoral inflammatory reaction patterns; grade 3 (5<=LR+<10), rhabdoid, tumor
      giant cell, enlarged vascular space, and/or hereditary leiomyomatosis renal cell
      carcinoma (HLRCC)-like patterns; grade 4 (LR+>=10), sarcomatoid, infiltrative
      growth patterns, and lymphatic invasion. In the principal cohort, 3-tier (grades
      1-2, 3, and 4) and 4-tier architectural scores outperformed World Health
      Organization/International Society of Urological Pathology, and World Health
      Organization/ International Society of Urological Pathology+necrosis gradings for
      DFS and CSS, and constituted an independent predictor for DFS (hazard ratio
      [HR]=5.91; P<6.7E-10) and CSS (HR=4.49; P=2.2E-03), retained in the localized
      (pT1-3N0M0) ccRCC subgroup (HR=6.10; P=1.3E-07 for DFS, and HR=20.09; P=9.4E-05
      for CSS). On comparing with integrated staging systems, architectural grade with
      1 morphologic datum remained an independent predictor of CSS, as did University
      of California Los Angeles Integrated Staging System and SSIGN, and was associated
      with the highest HR (HR=2.60; P=9.1E-04 in all patients; HR=4.38; P=2.0E-05 in
      the localized ccRCC subgroup). Architecture-based score for ccRCC outperforms all
      other morphologic grading systems and constitutes an independent predictor for
      DFS and CSS. As the predictive values of 3-tier and 4-tier architecture-based
      scores were similar throughout the study, we proposed to keep the simplified
      version as the final score, and to define 3 risk groups as follows: low risk
      (grades 1 to 2), intermediate risk (grade 3), and high risk (grade 4).

PMID- 29356728
TI  - Obstructive Sleep Apnea Syndrome: Implications for Primary Care.

PMID- 29356724
TI  - NUTM1 Gene Fusions Characterize a Subset of Undifferentiated Soft Tissue and
      Visceral Tumors.
AB  - NUT midline carcinoma is an aggressive tumor that occurs mainly in the head and
      neck and, less frequently, the mediastinum and lung. Following identification of
      an index case of a NUTM1 fusion positive undifferentiated soft tissue tumor, we
      interrogated additional cases of primary undifferentiated soft tissue and
      visceral tumors for NUTM1 abnormalities. Targeted next-generation sequencing was
      performed on RNA extracted from formalin-fixed paraffin-embedded tissue, and
      results validated by fluorescence in situ hybridization using custom bacterial
      artificial chromosome probes. Six patients were identified: mean age of 42 years
      (range, 3 to 71 y); equal sex distribution; and, tumors involved the extremity
      soft tissues (N=2), kidney (N=2), stomach, and brain. On systemic work-up at
      presentation all patients lacked a distant primary tumor. Morphologically, the
      tumors were heterogenous, with undifferentiated round-epithelioid-rhabdoid cells
      arranged in solid sheets, nests, and cords. Mitotic activity was generally brisk.
      Four cases expressed pancytokeratin, but in only 2 cases was this diffuse. Next
      generation sequencing demonstrated the following fusions: BRD4-NUTM1 (3 cases),
      BRD3-NUTM1, MXD1-NUTM1, and BCORL1-NUTM1. Independent testing by fluorescence in
      situ hybridization confirmed the presence of NUTM1 and partner gene
      rearrangement. This study establishes that NUT-associated tumors transgress the
      midline and account for a subset of primitive neoplasms occurring in soft tissue
      and viscera. Tumors harboring NUTM1 gene fusions are presumably underrecognized,
      and the extent to which they account for undifferentiated mesenchymal,
      neuroendocrine, and/or epithelial neoplasms is unclear. Moreover, the
      relationship, if any, between NUT-associated tumors in soft tissue and/or
      viscera, and conventional NUT carcinoma, remains to be elucidated.

PMID- 29356729
TI  - Literature Review.

PMID- 29356732
TI  - Laparoscopic Surgery's 100 Most Influential Manuscripts: A Bibliometric Analysis.
AB  - PURPOSE: Bibliometric analysis of the 100 most cited manuscripts in laparoscopic
      surgery. MATERIALS AND METHODS: Web of Science database was used to identify all
      English language full manuscripts with search terms "laparoscop*" and "surg*."
      The 100 most cited publications were analyzed by; topic, journal, author, year,
      and institution. RESULTS: In total, 71,524 eligible papers were returned with a
      median citation of 585.76. The 2 most cited papers received 1635 citations each.
      Nelson and colleagues, compared laparoscopic with open colectomy for malignancy,
      and Clavien and colleagues, classified postoperative morbidity by severity.
      Annals of Surgery published the largest number of papers (n=22), and received
      most citations (n=12,356). The United States (n=55) and 2004 (n=13) had the
      highest number of publications. The most ubiquitous topic was cancer treatment
      (n=35), followed by surgical technique (n=24), and comparison of laparoscopic
      with open surgery (n=22). CONCLUSIONS: The most cited topic compared laparoscopic
      surgical techniques and comparisons thereof with open surgery.

PMID- 29356733
TI  - Cardiopulmonary Aerobic Fitness Assessment During Maximal and Submaximal Exercise
      Testing in Pediatric Oncology Patients After Chemotherapy.
AB  - PURPOSE: The cardiopulmonary exercise test (CPET) is a valuable tool to assess
      cardiopulmonary exercise capacity in pediatric oncology patients after
      chemotherapy. In addition, few studies on the utility of submaximal testing have
      been performed, which could be important as some patients are unable to complete
      a maximal effort test secondary to deconditioning by both disease and treatment.
      MATERIALS AND METHODS: We performed a retrospective chart review of pediatric
      cancer patients exposed to chemotherapy from 1992 to 2013 who underwent CPET with
      cycle ergometry (n=27). The study patients were compared with age-matched, sex
      matched, and size-matched normal controls. The submaximal measure recorded was
      the oxygen consumption (VO2)@respiratory exchange ratio (RER) 1.0 during a
      maximal effort test. RESULTS: The chemotherapy group demonstrated significantly
      lower exercise time (9.2+/-3.6 vs. 11.4+/-3.8; P=0.008), total work capacity
      (4914.4+/-3290.3 vs. 7664.4+/-4289.5; P=0.004), systolic blood pressure at peak
      exercise (162.9+/-23.2 vs. 177.3+/-23.8; P=0.01), indexed peak VO2 (33.9+/-6.9
      vs. 40.0+/-6.3; P=0.001), and indexed peak oxygen pulse (6.1+/-1.3 vs. 7.0+/-1.5;
      P=0.004)). For the submaximal outcome measured, 11/27 of the chemotherapy
      patients had VO2@RER 1.0 values <-2 SD from the mean compared with 0/27 control
      patients. CONCLUSIONS: Pediatric patients exposed to chemotherapy have impaired
      cardiopulmonary exercise capacity. The VO2@RER 1.0 in chemotherapy patients
      suggests that this may be a reliable submaximal measure in this population.
      IMPLICATIONS FOR CANCER SURVIVORS: This study demonstrates that the CPET can be
      used in pediatric cancer survivors with prior exposure to chemotherapy to
      demonstrate impaired cardiopulmonary exercise tolerance, which is demonstrated on
      submaximal and maximal effort testing.

PMID- 29356734
TI  - Differentiation of Recurrent/Residual Glioma From Radiation Necrosis Using Semi
      Quantitative 99mTc MDM (Bis-Methionine-DTPA) Brain SPECT/CT and Dynamic
      Susceptibility Contrast-Enhanced MR Perfusion: A Comparative Study.
AB  - PURPOSE: In this study, Tc MDM (bis-methionine-DTPA) SPECT was used for the
      detection and differentiation of recurrent/residual glioma from radiation
      necrosis and the results were compared with dynamic susceptibility contrast
      enhanced (DSCE)-MRI and clinical findings. MATERIALS AND METHODS: Twenty-eight
      patients (18 men and 10 women; mean +/- SD age, 41.4 +/- 15.03 years) with
      histologically proven glioma (grade IV, 14; grade III, 7; grade II, 7) who were
      planned for postsurgical standard radio/chemo therapy were recruited
      prospectively. All the patients underwent technetium Tc MDM SPECT/CT and DSCE-MRI
      imaging at 6 months after surgery/radio-chemotherapy, 9 of 28 patients also
      underwent SPECT imaging at 1 to 2 weeks after surgery. RESULTS: Tc MDM SPECT/CT
      analysis demonstrated significantly higher target to nontarget (T/NT) ratio of
      the radiotracer in tumor recurrence than in radiation necrosis (3.59 +/- 1.70 vs
      1.16 +/- 0.42). Likewise, the normalized cerebral blood volume (nCBV) values in
      patients with tumor recurrence were also significantly higher than in radiation
      necrosis (5.16 +/- 2.30 vs 1.63 +/- 0.94). A positive correlation (rho = 0.823, P
      < 0.0001) between T/NT ratios and nCBV was observed. The cutoff T/NT ratios and
      nCBV values estimated by receiver operating characteristic analysis were greater
      than 1.50 (area under the curve, 0.944 +/- 0.34) and greater than 2.12 (area
      under the curve, 0.931 +/- 0.39), respectively. Combining the results of Tc MDM
      SPECT/CT, DSCE-MRI, and clinical findings, diagnosis of recurrent/residual glioma
      or radiation necrosis was made in 18 and 10 patients, respectively. Sensitivity
      and specificity of 2 techniques were comparable, that is, 92.0%: 78.6% for MDM
      SPECT/CT and of 92.0%: 71.4% for DSCE-MRI, respectively. CONCLUSION: Thus,
      combining MDM SPECT with DSCE MRI may provide an accurate method for
      differentiation of tumor recurrence from radiation-induced necrosis in glioma
      patients.

PMID- 29356735
TI  - Flare on Serial Prostate-Specific Membrane Antigen-Targeted 18F-DCFPyL PET/CT
      Examinations in Castration-Resistant Prostate Cancer: First Observations.
AB  - A 71-year-old man with castration-resistant prostate cancer demonstrated a flare
      phenomenon on Tc-MDP and CT after 10 weeks of enzalutamide. Prostate-specific
      membrane antigen-targeted F-DCFPyL PET/CT demonstrated minimal uptake at sites of
      baseline bone and lymph node disease with increasing uptake at sites of osseous
      disease following therapy. Although this is likely related in part to decreased
      androgen receptor activity and a consequent increase in prostate-specific
      membrane antigen expression, other mechanisms (neovascularization, cell
      infiltration from the bone repair process, osteoblastic turnover, or minimal
      radiotracer impurity) may also be involved in causing the increased F-DCFPyL
      uptake at sites of osseous flare.

PMID- 29356736
TI  - Anaplastic Thyroid Cancer With Extensive Skeletal Muscle Metastases on 18F-FDG
      PET/CT.
AB  - A 61-year-old woman with newly diagnosed anaplastic thyroid cancer and known
      metastases to the brain, lungs, and adrenal glands complained of groin muscle
      pain. F-FDG PET/CT was performed to assess for extent of disease and showed
      extensive hypermetabolic lesions throughout the skeletal musculature concerning
      for metastatic disease. As this would be a very rare presentation for anaplastic
      thyroid carcinoma, a biopsy of the left gluteal muscle was conducted. Pathology
      demonstrated anaplastic thyroid carcinoma, metastatic to skeletal muscle.

PMID- 29356737
TI  - Rare Variant of Intravascular Large B-Cell Lymphoma With Hemophagocytic Syndrome.
AB  - Intravascular lymphoma (IVL) is a rare subtype of diffuse large B-cell lymphoma
      characterized by a clonal proliferation of lymphocytes restricted to the
      intravascular space. We present the case of a 60-year-old man with hemophagocytic
      syndrome secondary to IVL. F-FDG PET/CT demonstrated hepatosplenomegaly with
      marked diffuse hepatic, splenic, and bone marrow hypermetabolism. The case report
      illustrates the imaging findings of this uncommon variant of IVL.

PMID- 29356738
TI  - Rhabdomyosarcoma Revealed by a Breast Metastasis.
AB  - A 38-year-old woman was referred for staging of an alveolar rhabdomyosarcoma
      revealed by a breast metastasis with unknown primary. Whole-body F-FDG PET/CT
      localized the primary tumor as an asymptomatic soft tissue lesion of the right
      foot with a significant uptake. PET/CT detected hepatic and pancreatic metastases
      and also showed a multifocal bone marrow involvement, which was not detected by
      the contrast-enhanced CT. These results led to a significant change in treatment
      management as the patient received local radiotherapy of the primitive lesion and
      polychemotherapy.

PMID- 29356739
TI  - Prostate Cancer Lytic Bone Metastases Imaged With 18F-Fluorocholine PET/CT.
AB  - A 76-year-old man with metastatic prostate cancer and back pain was referred for
      palliative radiotherapy. Staging F-fluorocholine PET/CT scan revealed
      fluorocholine-avid prostate mass, extensive lymphadenopathy, lung nodules, and
      extensive osteolytic lesions throughout the axial skeleton. Prostate cancer bone
      metastases are predominantly sclerotic in nature. We present F-fluorocholine
      PET/CT imaging of prostate cancer with very rare lytic bone metastases.

PMID- 29356740
TI  - Incidental Detection of a Melanoma by 18F-Fluorocholine PET/CT Performed for
      Evaluation of Primary Hyperparathyroidism.
AB  - An 80-year-old woman was evaluated with F-fluorocholine PET/CT in suspicion of a
      parathyroid adenoma. No focal parathyroid tracer uptake suggestive of adenoma was
      found, and instead a unilateral multinodular goiter without elevated F
      fluorocholine uptake was diagnosed. In addition, focal uptake was found in a
      cutaneous nodule dorsally on the right shoulder. Upon pathological evaluation,
      this proved to be a malignant melanoma.

PMID- 29356741
TI  - Tumor Cystic Necrosis Following Peptide Receptor Radionuclide Therapy in
      Neuroendocrine Tumors.
AB  - The response assessment to peptide receptor radionuclide therapy (PRRT) in
      neuroendocrine tumors is complex. We present the case of a 49-year-old man with
      metastatic rectal neuroendocrine tumor whose clinical symptoms and response
      evaluation criteria in solid tumors suggested progressive disease following PRRT.
      However, Ga-DOTA-(Tyr3)-octreotate PET/CT showed a partial scintigraphic response
      with absence of F-FDG PET/CT uptake consistent with tumor cystic necrosis. Long
      term follow-up confirmed ongoing tumor response to treatment. Utilizing all
      modalities of response assessment seems to be important in correctly judging the
      benefit from PRRT and will need to be incorporated when developing response
      assessment tools.

PMID- 29356742
TI  - 18F-FDG PET/CT Detected Delayed Endoleak in an Aortoiliac Endovascular Aneurysm
      Repair.
AB  - We present a case of a type Ia endoleak detected using F-FDG PET/CT 10 years
      after an abdominal aortoiliac endovascular aneurysm repair in an 83-year-old man.
      The F-FDG PET/CT scan was performed to evaluate a solitary pulmonary nodule but,
      in addition, demonstrated unexpected blood pool activity outside the stent graft
      and within the abdominal aortic aneurysm sac, indicating an endoleak; no FDG
      activity should be present within the aneurysm sac after stent graft placement. A
      subsequent CT angiogram confirmed the endoleak. This case illustrates the value
      of PET/CT in unexpectedly demonstrating this serious, late complication of
      endovascular aneurysm repair.

PMID- 29356743
TI  - 18F-NaF PET/CT Finding in a Patient With Abdominal Discomfort After
      Schistosomiasis.
AB  - A 77-year-old man with back pain and abdominal distention underwent F-NaF PET/CT
      examination to evaluate potential bone lesions. Multiple foci of increased
      activity were noted in the chest, which corresponded to bilateral ribs and
      suggested possible occult fractures. Surprisingly, increased F-NaF uptake was
      observed in the region of pelvis, which corresponded to calcification along the
      colon wall, a sequela of intestinal Japanese schistosomiasis that the patient
      experienced 30 years ago.

PMID- 29356744
TI  - Initial Clinical Investigation of [18F]Tetrafluoroborate PET/CT in Comparison to
      [124I]Iodine PET/CT for Imaging Thyroid Cancer.
AB  - AIM: Recently, [F]tetrafluoroborate ([F]TFB) has been introduced as a versatile
      PET probe for imaging the human sodium/iodide symporter activity. This pilot
      study aimed to compare [F]TFB-PET/CT with [I]NaI-PET/CT imaging in thyroid cancer
      patients. METHODS: Nine patients with newly diagnosed differentiated thyroid
      cancer underwent both [F]TFB- and [I]NaI-PET/CT after total thyroidectomy. PET/CT
      scans were visually analyzed for the presence of remnant thyroid tissue and for
      metastatic lesions on a patient and lesion basis. For semiquantitative analysis,
      thyroid remnant/tumor to blood pool ratios were calculated. RESULTS: All patients
      presented with positive [F]TFB and [I]NaI-PET/CT scans. Retention of I in remnant
      thyroid tissue was significantly higher as compared with [F]TFB (P < 0.01). In a
      lesion-based analysis, both tracers identified an almost equal number of foci
      with [F]TFB depicting a total of 41 foci and I a total of 40 foci, respectively.
      In 6 of 9 patients, both radiopharmaceuticals returned an identical number of
      foci. Two I-positive benign thyroid remnants were missed by [F]TFB-PET/CT in a
      single patient. In another case, both tracers identified different thyroid
      remnant tissues in the cervical region. Notably, [F]TFB demonstrated additional
      (I-negative) cervical lymph node metastases in 2 patients, leading to an overall
      agreement between the radiotracers of 91% (74/81 foci). DISCUSSION: In this pilot
      study, [F]TFB-PET was not inferior to [I]NaI-PET for detecting thyroid cancer and
      its metastases and was able to detect [I]NaI-PET-negative viable differentiated
      thyroid cancer metastases. Further clinical evaluation as a PET tracer for
      imaging thyroid pathophysiology and human sodium/iodide symporter expressing
      neoplasms is highly warranted.

PMID- 29356745
TI  - Virchow Node From Prostate Carcinoma by 18F-Choline PET/CT.
AB  - F-choline PET/CT is increasingly being used during the follow-up of prostate
      cancer and is bringing us valuable information for the delineation of local and
      distant nodal recurrence in patients with hormone-resistant poorly differentiated
      cell types. Lymphatic spreading usually involves pelvic and retroperitoneal
      levels, being unusual at supraclavicular levels. We report a 75-year-old man with
      unsuspected involvement of Virchow node from prostate cancer observed using F
      choline PET/CT.

PMID- 29356746
TI  - Back Pain in a Patient With Parotid Carcinoma: Serendipitous Discovery of Acute
      Pancreatitis as the Cause on 18F-FDG PET/CT.
AB  - Nonmalignant incidental findings in patients undergoing F-fluorodeoxyglucose (F
      FDG) PET/CT for oncological indication are common. Here, we present such a case
      of a 40-year-old woman, treated case of adenoid cystic carcinoma of the left
      parotid gland, who subsequently presented with progressive back pain and deranged
      liver function tests. F-FDG PET/CT showed no definite malignancy but incidental
      finding of moderately severe acute pancreatitis, which was the cause of back
      pain.

PMID- 29356747
TI  - Posterior Reversible Encephalopathy Syndrome on 18F-FDG PET/CT in a Pediatric
      Patient With Burkitt's Lymphoma.
AB  - We present a case of posterior reversible encephalopathy syndrome (PRES) in a
      pediatric patient with Burkitt's lymphoma predominantly involving the bone
      marrow. F-FDG PET/CT scan obtained after the first cycle of chemotherapy,
      complicated by acute kidney injury, hypertension, tumor lysis syndrome, and
      lethargy with focal neurological symptoms, showed a favorable marrow and lymph
      node response but increased FDG uptake in the bilateral frontal and occipital
      cortical/subcortical regions. Brain MRI was consistent with PRES. The patient was
      managed with IV hydration and blood pressure control with symptom resolution.
      This case shows the F-FDG uptake pattern of PRES in postchemotherapy setting.

PMID- 29356749
TI  - Key Factors Leading to Program Selection: A Survey of Physician Assistant Program
      Interviewees.
AB  - PURPOSE: The purpose of this study was to determine which factors had the
      greatest influence on physician assistant (PA) interviewees' decision to choose a
      PA program to attend. The information in this article may assist PA programs in
      making their program more attractive to potential applicants and also may help
      applicants identify programs that will best fit their needs. METHODS: Applicants
      who interviewed with a PA program were asked to rate 33 different influential
      factors when choosing a program to attend. RESULTS: Respondents most highly
      endorsed quality of faculty and staff, first-time Physician Assistant National
      Certifying Examination pass rates, and morale of faculty and staff. Results
      varied by demographics, including marital status, age, and sex of respondent.
      Results also varied from pre-PA students. CONCLUSIONS: Although there are
      numerous factors involved in program selection, PA programs may want to focus on
      the quality and morale of their faculty and staff to help improve the likelihood
      of attracting and retaining the highest quality applicants.

PMID- 29356748
TI  - Primary Spleen Angiosarcoma With Concomitant Hepatic Hemangiomas on 18F-FDG
      PET/CT.
AB  - A staging FDG PET/CT was performed for a 43-year-old woman who was suspected to
      have splenic malignancy with multiple hepatic metastases revealed on CT images.
      The PET/CT images showed the masses and nodules of spleen had mildly increased
      uptake of FDG, whereas the uptake by the hepatic lesions was slightly higher.
      However, the pathologic evaluation demonstrated that splenic lesion was malignant
      as angiosarcoma, but the hepatic lesions were benign as hemangiomas.

PMID- 29356750
TI  - Factors Influencing Physician Assistant Students' Attitudes Toward Deservingness
      of Care for Undocumented Mexicans.
AB  - PURPOSE: Attitudes regarding health-related deservingness of care for vulnerable
      patient populations can impact the quality of services provided. This study was
      aimed at identifying the influences that shape these attitudes among physician
      assistant (PA) students. METHODS: The study focused on PA students' perspectives
      toward care for a particularly vulnerable population, undocumented Mexican
      immigrants. An in-person survey was administered to first- and second-year PA
      students (n = 75). Multiple regression was used to assess whether familiarity,
      stereotyping, language skills, cultural preparedness, societal views, and
      background characteristics of PA students influenced attitudes toward
      deservingness of care. RESULTS: Results suggested that cultural preparedness
      among PA students was associated with positive views toward deservingness of both
      emergency services (beta = 0.38, p < .001) and primary care (beta = -0.211, p =
      .05) for undocumented Mexicans. Negative societal views toward this population
      predicted an unwillingness to endorse emergency care (beta = -0.43, p < .001) and
      primary care (beta = -0.45, p < .001). CONCLUSIONS: Demographic projections
      indicate continued trends toward increasingly diverse patient populations, with
      dramatic growth among Hispanics. The findings of this study suggest that greater
      cultural preparedness is needed for future PAs. Furthermore, strategies for
      increasing PA students' self-awareness of how their broader societal views shape
      service delivery are warranted to ensure equitable care.

PMID- 29356751
TI  - Knowing Your Worth: Salary Expectations and Gender of Matriculating Physician
      Assistant Students.
AB  - PURPOSE: The male-female wage gap is present and persistent in the health care
      sector, even among physician assistants (PAs). Explanations for the persistent
      gender earnings gap include differential salary expectations of men and women
      based, in part, on women's lower pay entitlement. The purpose of this study was
      to examine differences in salary expectations between male and female
      matriculating PA students nationwide, adjusting for other factors expected to
      affect salaries and pay expectations of both male and female matriculants.
      METHODS: Using data from the Physician Assistant Education Association
      Matriculating Student Survey of 2013, 2014, and 2015, we investigated the
      relationship between first-year PA students' gender and their salary expectations
      after graduation using a multinomial logistic regression analysis. We controlled
      for possible confounders by including independent variables measuring student
      demographics, background characteristics, qualifications, future career plans,
      and financial considerations. RESULTS: We found that female PA students were less
      likely than male PA students to expect a salary of $80,000-$89,999 (Odds Ratio
      [OR] = 0.73), $90,000-$99,999 (OR = 0.58), or $100,000 or greater (OR = 0.42) in
      comparison to an expected salary of less than $70,000, when controlling for our
      independent variables. CONCLUSIONS: Our analysis shows that on entry into PA
      training programs, female PA students' earnings expectations are less than those
      of male PA students. Our results are consistent with research, suggesting that
      women typically expect lower pay and systematically undervalue their
      contributions and skills in comparison to men. Physician assistant programs
      should consider strategies to promote realistic salary expectations among PA
      students as one way to promote earnings equity.

PMID- 29356752
TI  - From the Editor.

PMID- 29356753
TI  - Case in Health Care Management.

PMID- 29356754
TI  - Professional Values Competency Evaluation: Comparing Student Written Assignments
      to Literature Findings.
AB  - Nurse educators have had no clear evidence-based method to evaluate student
      competency related to professional values. This article describes a comparative
      analysis in which the list of professional values identified in a research study
      of undergraduate prelicensure nursing student assignments was compared with a
      list identified in an integrative review of nursing literature. Comparative
      analysis allowed for a categorization of professional values that were either
      congruent between student assignments and literature, exclusively evident in
      literature, or exclusively evident in student assignments. Findings may
      contribute to curricular process improvements promoting professional values
      development in undergraduate nursing students.

PMID- 29356755
TI  - The effects of physical activity on survival in patients with colorectal cancer.
AB  - Mortality from colorectal cancer has been declining over the past 20 years due to
      improvements in screening and treatment. Physical activity improves patient
      quality of life, slows functional decline, and reduces all-cause mortality.
      Although some patients may have difficulty participating in physical activity,
      clinicians should always try to incorporate exercise into a management plan for
      patients who have survived colorectal cancer.

PMID- 29356756
TI  - Primary care providers' role in transgender healthcare.

PMID- 29356757
TI  - Pro- versus Antinociceptive Nongenomic Effects of Neuronal Mineralocorticoid
      versus Glucocorticoid Receptors during Rat Hind Paw Inflammation.
AB  - BACKGROUND: In naive rats, corticosteroids activate neuronal membrane-bound
      glucocorticoid and mineralocorticoid receptors in spinal cord and periphery to
      modulate nociceptive behavior by nongenomic mechanisms. Here we investigated
      inflammation-induced changes in neuronal versus glial glucocorticoid and
      mineralocorticoid receptors and their ligand-mediated nongenomic impact on
      mechanical nociception in rats. METHODS: In Wistar rats (n = 5 to 7/group) with
      Freund's complete adjuvant hind paw inflammation, we examined glucocorticoid and
      mineralocorticoid receptor expression in spinal cord and peripheral sensory
      neurons versus glial using quantitative reverse transcription-polymerase chain
      reaction (qRT-PCR), Western blot, immunohistochemistry, and radioligand binding.
      Moreover, we explored the expression of mineralocorticoid receptors protecting
      enzyme 11-betahydroxysteroid dehydrogenase type 2 as well as the nociceptive
      behavioral changes after glucocorticoid and mineralocorticoid receptors agonist
      or antagonist application. RESULTS: Hind paw inflammation resulted in significant
      upregulation of glucocorticoid receptors in nociceptive neurons of spinal cord
      (60%) and dorsal root ganglia (15%) as well as mineralocorticoid receptors, while
      corticosteroid plasma concentrations remained unchanged. Mineralocorticoid (83 +/
      16 fmol/mg) but not glucocorticoid (104 +/- 20 fmol/mg) membrane binding sites
      increased twofold in dorsal root ganglia concomitant with upregulated 11
      betahydroxysteroid dehydrogenase type 2 (43%). Glucocorticoid and
      mineralocorticoid receptor expression in spinal microglia and astrocytes was
      small. Importantly, glucocorticoid receptor agonist dexamethasone or
      mineralocorticoid receptor antagonist canrenoate-K rapidly and dose-dependently
      attenuated nociceptive behavior. Isobolographic analysis of the combination of
      both drugs showed subadditive but not synergistic or additive effects.
      CONCLUSIONS: The enhanced mechanical sensitivity of inflamed hind paws
      accompanied with corticosteroid receptor upregulation in spinal and peripheral
      sensory neurons was attenuated immediately after glucocorticoid receptor agonist
      and mineralocorticoid receptor antagonist administration, suggesting acute
      nongenomic effects consistent with detected membrane-bound corticosteroid
      receptors.

PMID- 29356758
TI  - Global scientific productivity in the field of PET: a 10-year survey of research
      activities.
AB  - OBJECTIVE: The objective of this study was to assess global research output in
      the field of PET and to provide a general picture of PET research. MATERIALS AND
      METHODS: Publications on PET from 2007 to 2016 were identified using the Web of
      Science. The total number of papers, the number of papers adjusted by gross
      domestic product (GDP)/population size, total citations, and average citations
      were investigated. RESULTS: A total of 40 670 papers were identified in the field
      of PET between 2007 and 2016. The number of papers published per year were
      significantly increased during this period (P=0.000). High-income countries
      published the maximum papers (89.95%), followed by middle-income countries
      (10.05%), whereas no papers were published by authors from low-income countries.
      The USA published the largest number of papers (11 936), followed by Japan
      (3667), Germany (3424), China (2508), and the UK (2424), and the USA had the
      highest total number of citations (361 498). The UK had the highest average
      citations (31.81). Positive correlations were found between the total number of
      papers and GDP (P=0.000, r=0.909)/population (P=0.000, r=0.772). When normalized
      by GDP, Denmark ranked the first (23.56), followed by The Netherlands (17.18) and
      Belgium (15.32). When adjusted for population, Denmark ranked the first (111.55),
      followed by The Netherlands (87.91) and Switzerland (86.93). CONCLUSION: Global
      scientific production represents a rapid increase in the PET field in recent
      years. The majority of PET papers are from high-income countries. The USA is the
      most prolific country, whereas some smaller European countries may be more
      prolific relative to their GDP/population.

PMID- 29356759
TI  - Modified Primary Prophylaxis in Previously Untreated Patients With Severe
      Hemophilia A in Iran.
AB  - BACKGROUND: Recently the low-dose tailoring method of primary prophylaxis has
      been introduced for previously untreated patients with hemophilia A. OBJECTIVE:
      To evaluate the efficacy and safety of low-dose tailoring method of primary
      prophylaxis in previously untreated patients with severe hemophilia A. MATERIALS
      AND METHODS: In this pre-post interventional study, 33 patients with severe
      hemophilia A who were previously untreated and affiliated to universities in the
      capital city and southern Iran were evaluated during 2014 to 2015. Modified
      primary continuous prophylaxis was used for patients with age below 3 years old,
      after first and before the second episodes of obvious clinical bleeding in large
      joints or large soft tissue hematoma or large amount of bleeding. Prophylaxis was
      started by 25 IU/kg once per week and increased to twice or 3 times a week
      according to defined bleeding events. RESULTS: The median age at diagnosis and
      age of starting prophylaxis were: 4 months (at birth, 22 mo) and 12 months (1 to
      35 mo), respectively. Mean annual bleeding rate of patients after prophylaxis was
      1.08+/-2.21 episodes per year. None of the patients had inhibitors before
      therapy. Inhibitor was present in 5 patients (15.1%) after prophylaxis.
      CONCLUSIONS: It seems that modified primary continuous prophylaxis has been
      successful in reducing bleeding episodes in children with severe hemophilia A and
      in the texture of lower cost it can improve quality of life of these patients,
      especially in developing countries where financial resources are limited.

PMID- 29356760
TI  - Comparison of the Radiologic and Clinical Findings of Adolescents With Breast
      Complaints.
AB  - INTRODUCTION: The American College of Radiology's Breast Imaging Reporting and
      Data System (BI-RADS) was developed to guide imaging-based surgical treatment in
      patients with breast cancer. Studies confirming the BI-RADS did not include
      adolescents. To evaluate the validity of this classification system in
      adolescents, we aim to investigate the relationship between the BI-RADS and
      pathology findings in adolescents. METHODS: The medical data of 67 female
      adolescent patients, aged 12 to 18, referred to our clinic for breast-related
      complaints between 2013 and 2016 were reviewed retrospectively for demographic
      data and the results of radiologic and surgical pathologies. RESULTS: The main
      underlying reasons for the visit at the clinic were fullness, tenderness, pain,
      and palpable masses. Of the 67 patients, 46 were enrolled in the study. After
      breast ultrasonography, patients whose complaints had diminished were subtracted
      from the follow-up. The mean age of the patients was 16 years (12 to 18 y). The
      mean mass diameter size was 3.69 cm (0.9 to 15 cm), and the mean clinical follow
      up was 65.3 days (11 to 1095 d). All the patients who were surgically intervened
      had benign pathology. Of the 21 surgically intervened patients with BI-RADS
      levels of >=3, most had fibroadenomas. CONCLUSIONS: The BI-RADS classification
      based treatment algorithm may not be valid in adolescents. In the present study,
      all patients with lesions with BI-RADS >=3 levels had revealed benign
      pathologies. The BI-RADS classification may show an increased risk. However, to
      determine the need for a biopsy in adolescents, there is a need for larger-scale
      pediatric and adolescent studies using the BI-RADS classification.

PMID- 29356761
TI  - Moxifloxacin in Pediatric Patients With Complicated Intra-abdominal Infections:
      Results of the MOXIPEDIA Randomized Controlled Study.
AB  - BACKGROUND: This study was designed to evaluate primarily the safety and also the
      efficacy of moxifloxacin (MXF) in children with complicated intra-abdominal
      infections (cIAIs). METHODS: In this multicenter, randomized, double-blind,
      controlled study, 451 pediatric patients aged 3 months to 17 years with cIAIs
      were treated with intravenous/oral MXF (N = 301) or comparator (COMP, intravenous
      ertapenem followed by oral amoxicillin/clavulanate; N = 150) for 5 to 14 days.
      Doses of MXF were selected based on the results of a Phase 1 study in pediatric
      patients (NCT01049022). The primary endpoint was safety, with particular focus on
      cardiac and musculoskeletal safety; clinical and bacteriologic efficacy at test
      of cure was also investigated. RESULTS: The proportion of patients with adverse
      events (AEs) was comparable between the 2 treatment arms (MXF: 58.1% and COMP:
      54.7%). The incidence of drug-related AEs was higher in the MXF arm than in the
      COMP arm (14.3% and 6.7%, respectively). No cases of QTc interval prolongation
      related morbidity or mortality were observed. The proportion of patients with
      musculoskeletal AEs was comparable between treatment arms; no drug-related events
      were reported. Clinical cure rates were 84.6% and 95.5% in the MXF and COMP arms,
      respectively, in patients with confirmed pathogen(s) at baseline. CONCLUSIONS:
      MXF treatment was well tolerated in children with cIAIs. However, a lower
      clinical cure rate was observed with MXF treatment compared with COMP. This study
      does not support a recommendation of MXF for children with cIAIs when alternative
      more efficacious antibiotics with better safety profile are available.

PMID- 29356762
TI  - Update on Neonatal Herpes Simplex Epidemiology in the Netherlands: A Health
      Problem of Increasing Concern?
AB  - BACKGROUND: This article provides an update on the incidence of neonatal herpes,
      guideline adherence by health care professionals (HCP) and trends in genital
      herpes simplex virus (HSV) infection during pregnancy in the Netherlands.
      METHODS: Questionnaires were sent to all hospitals inquiring about numbers and
      characteristics of neonatal and maternal HSV infections, and guideline adherence
      between 2012 and 2015. Longitudinal trends were investigated from 1999 onward
      using survey data and Perinatal Registry of the Netherlands data (Perined).
      Trends were smoothed with Poisson regression splines. Risk indicators for
      neonatal and maternal HSV infections were examined with Poisson regression
      analyses. RESULTS: Neonatal herpes incidence was 4.8/100,000 live births based on
      survey data (2012-2015) and 3.4/100,000 based on Perined (2012-2014). Mortality
      rate was 23% (7/30). Neonatal herpes incidence increased slightly over time as
      did the prevalence of genital HSV infection among pregnant women. Non-Western
      ethnicity (Rate Ratio: 1.9; 95% confidence interval: 1.5-2.5) and age <20 years
      (Rate Ratio: 2.3; 95% confidence interval: 1.2-4.7) were associated with genital
      herpes during pregnancy. In Perined, none of the neonatal herpes cases had a
      mother diagnosed with an active genital herpes infection during pregnancy.
      Preventive measures to reduce vertical herpes transmission (such as cesarean
      section) were less commonly reported by HCP in 2012-2015 compared with 2006-2011.
      CONCLUSIONS: Neonatal herpes incidence in the Netherlands slowly increased over
      the last 15 years. An increased genital HSV prevalence during pregnancy or, to
      lower extent, the decreased guideline adherence by HCP may be responsible. A rise
      in asymptomatic maternal HSV shedding is also plausible, emphasizing the
      challenges in preventing neonatal herpes.

PMID- 29356763
TI  - Temporal Improvements in Long-term Outcome in Care Among HIV-infected Children
      Enrolled in Public Antiretroviral Treatment Care: An Analysis of Outcomes From
      2004 to 2012 in Zimbabwe.
AB  - BACKGROUND: Increasing numbers of children are requiring long-term HIV care and
      antiretroviral treatment (ART) in public ART programs in Africa, but temporal
      trends and long-term outcomes in care remain poorly understood. METHODS: We
      analyzed outcomes in a longitudinal cohort of infants (<2 years of age) and
      children (2-10 years of age) enrolling in a public tertiary ART center in
      Zimbabwe over an 8-year period (2004-2012). RESULTS: The clinic enrolled 1644
      infants and children; the median age at enrollment was 39 months (interquartile
      range: 14-79), with a median CD4% of 17.0 (interquartile range: 11-24) in infants
      and 15.0 (9%-23%) in children (P = 0.0007). Among those linked to care, 33.5%
      dropped out of care within the first 3 months of enrollment. After implementation
      of revised guidelines in 2009, decentralization of care and increased access to
      prevention of mother to child transmission services, we observed an increase in
      infants (48.9%-68.3%; P < 0.0001) and children (48.9%-68.3%; P < 0.0001)
      remaining in care for more than 3 months. Children enrolled from 2009 were
      younger, had lower World Health Organization clinical stage, improved baseline
      CD4 counts than those who enrolled in 2004-2008. Long-term retention in care also
      improved with decreasing risk of loss from care at 36 months for infants enrolled
      from 2009 (aHR: 0.57; 95% confidence interval: 0.34-0.95; P = 0.031). ART
      eligibility at enrollment was a significant predictor of long-term retention in
      care, while delayed ART initiation after 5 years of age resulted in failure to
      fully reconstitute CD4 counts to age-appropriate levels despite prolonged ART.
      CONCLUSIONS: Significant improvements have been made in engaging and retaining
      children in care in public ART programs in Zimbabwe. Guideline and policy changes
      that increase access and eligibility will likely to continue to support
      improvement in pediatric HIV outcomes.

PMID- 29356764
TI  - Pediatric Nonalcoholic Fatty Liver Disease: Current Thinking.
AB  - Nonalcoholic fatty liver disease (NAFLD), an increasingly prevalent paediatric
      disorder, is diagnosed and managed not only by both pediatric
      gastroenterologists/hepatologists but also frequently by the general
      pediatrician. This article updates recent advances in diagnostic and therapeutic
      approach, which may be applied to everyday practice. Diagnosis of NAFLD takes
      into account the risk factor profile and is a diagnosis of exclusion. Techniques
      such as transient elastography and specific biomarkers aimed at improving
      diagnosis and monitoring of NAFLD need further validation in the pediatric
      population. Defining the risk to develop cirrhosis seems to be of primary
      importance already in childhood and a combination of genetic, clinical, and
      environmental factors can help in monitoring and making decisions on therapy.
      Weight reduction therapy should be the aim of treatment approach, but the
      compliance is poor and pharmacological treatment would be helpful;
      docosahexaenoic acid, some probiotics, and vitamin E are to be considered, but
      evidence is not sufficient to recommend widespread use.

PMID- 29356765
TI  - Resolving Malnutrition With Parenteral Nutrition Before Liver Transplant in
      Biliary Atresia.
AB  - OBJECTIVE: Malnutrition is a common complication of end-stage liver disease
      (ESLD) associated with poor liver transplant outcomes. Nasogastric feeds are used
      for nutritional supplementation, but some patients remain malnourished.
      Parenteral nutrition (PN) can be effective, but has potential complications. The
      primary objective was to evaluate the effect of PN on anthropometric measures in
      children with ESLD awaiting liver transplant. Secondary objectives were
      evaluation of PN-associated complications, liver function tests, pediatric end
      stage liver disease scores, waitlist time, and post-transplant length of stay
      (total and time in the intensive care unit). METHODS: A single-center,
      retrospective chart review analyzing pediatric patients with ESLD receiving PN
      who were transplanted during a 6-year period. Data were trended and described
      over time, as were the relationships between anthropometric data and time
      receiving PN. RESULTS: A total of 44 patients with ESLD were transplanted between
      January 2010 and December 2015. Eighteen (41%) received PN before transplant; all
      had biliary atresia with median age at transplant of 10 months (range, 5-18
      months). Mid-upper arm circumference and triceps skinfold thickness showed
      resolution of malnutrition in 7 patients (39%) with normalization of 1 measure in
      another 4 patients (22%). Of the remaining, 6 had improved z scores and 1 had
      worsening malnutrition. No deaths occurred in patients receiving PN. Central line
      infection rates were 3.8/1000 catheter days with 8 total infections in 6 patients
      over a total of 2117 catheter days. CONCLUSIONS: Children with ESLD and
      malnutrition who have failed enteral feeding may benefit from PN to improve
      and/or resolve malnutrition before liver transplant.

PMID- 29356767
TI  - Lack of Correlation of Liver Tests With Fibrosis Stage at Diagnosis in Pediatric
      Primary Sclerosing Cholangitis.
AB  - OBJECTIVES: The aims of this study were to characterize pediatric primary
      sclerosing cholangitis (PSC) at a regional referral-based institution, including
      scoring of biliary stricturing and liver fibrosis and correlation analyses of
      scores with serum liver tests, to identify biomarkers of disease severity.
      METHODS: A retrospective review of 39 PSC subjects was performed, with collection
      of demographic and outcomes data. Magnetic resonance cholangiopancreaticogram
      (MRCP) and liver biopsies were re-reviewed and scores of stricturing and fibrosis
      were correlated with serum liver tests. RESULTS: Average age at PSC diagnosis was
      11.2 years, 74% had inflammatory bowel disease and 51% had autoimmune hepatitis.
      Despite 83% with symptoms at presentation, only ~1/3 were symptomatic at a mean
      follow-up of 4.1 years. Using a validated MRCP biliary scoring system, the mean
      intrahepatic score was 1.1 (out of 4) and extrahepatic score was 1.0 (out of 3).
      The mean Ishak liver fibrosis stage was 3.5 (out of 6) and 33% had cirrhosis. 92%
      were alive with their native liver and 5% had a liver transplant. Serum biomarker
      analyses revealed no correlation between Ishak liver fibrosis stage or MRCP score
      and laboratory values. CONCLUSIONS: Pediatric PSC patients cared for at a
      regional referral center had relatively mild disease compared with previously
      published reports, with low MRCP stricture scores despite significant liver
      fibrosis. Liver tests at presentation did not correlate with MRCP stricture score
      or liver fibrosis stage, suggesting the need for future studies to identify
      potential biomarkers of disease severity.

PMID- 29356766
TI  - Sarcopenia in Children With End-Stage Liver Disease.
AB  - BACKGROUND: Sarcopenia, reflected by decreased psoas muscle surface area (PMSA),
      has been identified as a novel and independent predictor of wait-list mortality
      and outcomes in adult liver transplantation (LT). We hypothesized that children
      with end-stage liver disease (ESLD) would have smaller PMSA than healthy
      controls. METHODS: Computer tomography images of children (ages 0 to 18 years)
      listed for LT in 2015 and a control group comprised 2:1 age- and gender-matched
      healthy pediatric trauma victims were reviewed. PMSA was determined at 2
      intervertebral disc (L3/4; L4/5) levels. A subset of images was reviewed by 2
      radiologists to determine interrater correlation. RESULTS: A total of 23 children
      with ESLD were included, and the most prevalent diagnosis was biliary atresia
      (61%). On both lumbar levels, median PMSA was significantly smaller in ESLD
      subjects compared with the 46 healthy controls (L4/5; median total PMSA (tPMSA)
      407 mm (interquartile range 339-537) versus controls 513 mm (interquartile range
      437-672); P = 0.004), independent of participants' weight z scores (r = 0.01; P =
      0.95). Excellent interrater correlation was seen (intraclass correlation 0.99).
      CONCLUSIONS: In this retrospective pilot study, PMSA was significantly lower in
      children with ESLD compared with healthy age- and gender-matched controls.
      Because this finding was independent of growth in ESLD subjects, PMSA may
      represent a novel objective nutritional biomarker in children with advanced liver
      disease.

PMID- 29356768
TI  - Real-life Anti-tumor Necrosis Factor Experience in More Than 500 Patients: High
      Co-immunosuppression Rates But Low Rates of Quantifying Treatment Response.
AB  - OBJECTIVE: The aim of this study was to measure the effectiveness, safety, and
      use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel
      disease in the United Kingdom (UK). METHODS: Prospective UK audit of patients
      newly starting anti-TNF therapy. Disease severity was assessed using Physician
      Global Assessment +/or the Paediatric Crohn Disease Activity Index. RESULTS: A
      total of 37 centers participated (23/25 specialist pediatric inflammatory bowel
      disease sites). A total of 524 patients were included: 429 with Crohn disease
      (CD), 76 with ulcerative colitis (UC), and 19 with IBD unclassified (IBDU).
      Eighty-seven percent (488/562) of anti-TNF was infliximab; commonest indication
      was active luminal CD 77% (330/429) or chronic refractory UC/IBDU 56% (53/95);
      79% (445/562) had concomitant co-immunosuppression. In CD (267/429 male), median
      time from diagnosis to treatment was 1.42 years (interquartile range 0.63-2.97).
      Disease (at initiation) was moderate or severe in 91% (156/171) by Physician
      Global Assessment compared to 41% (88/217) by Paediatric Crohn Disease Activity
      Index (Kappa (kappa) 0.28 = only "fair agreement"; P < 0.001.Where documented,
      77% (53/69) of patients with CD responded to induction; and 65% (46/71) entered
      remission. A total of 2287 infusions and 301.96 years of patient' follow-up (n =
      385) are represented; adverse events affected 3% (49/1587) infliximab and 2%
      (2/98) adalimumab infusions (no deaths or malignancies). Peri-anal abscess
      drainage was less common after anti-TNF initiation (CD), that is 26% (27/102)
      before, 7% (3/42) after (P = 0.01); however, pre and post anti-TNF data
      collection was not over equal time periods. CONCLUSIONS: Anti-TNFs are effective
      treatments, usually given with thiopurine co-immunosuppression. This study
      highlights deficiencies in formal documentation of effect and disparity between
      disease severity scoring tools, which need to be addressed to improve ongoing
      patient care.

PMID- 29356771
TI  - Erratum.

PMID- 29356769
TI  - Enteroaggregative Escherichia coli Subclinical Infection and Coinfections and
      Impaired Child Growth in the MAL-ED Cohort Study.
AB  - OBJECTIVE: We evaluated the impact of subclinical enteroaggregative Escherichia
      coli (EAEC) infection alone and in combination with other pathogens in the first
      6 months of life on child growth. METHODS: Nondiarrheal samples from 1684
      children across 8 Multisite Birth Cohort Study, Malnutrition and Enteric Diseases
      (MAL-ED) sites in Asia, Africa, and Latin America were tested monthly; more than
      90% of children were followed-up twice weekly for the first 6 months of life.
      RESULTS: Children with subclinical EAEC infection did not show altered growth
      between enrollment and 6 months. Conversely, EAEC coinfection with any other
      pathogen was negatively associated with delta weight-for-length (P < 0.05) and
      weight-for-age (P > 0.05) z scores between 0 and 6 months. The presence of 2 or
      more pathogens without EAEC was not significantly associated with delta weight
      for-length and weight-for-age. The most frequent EAEC coinfections included
      Campylobacter spp, heat-labile toxin-producing enterotoxigenic E coli,
      Cryptosporidium spp, and atypical enteropathogenic E coli. Myeloperoxidase levels
      were increased with EAEC coinfection (P < 0.05). EAEC pathogen codetection was
      associated with lower neopterin levels compared to those of no-pathogen control
      children (P < 0.05). Mothers of children with EAEC coinfections had lower levels
      of education, poorer hygiene and sanitation, lower socioeconomic status, and
      lower breast-feeding rates compared to mothers of children in whom no pathogen
      was detected (P < 0.05). CONCLUSIONS: These data emphasize the public health
      importance of subclinical EAEC infection in early infancy in association with
      other pathogens and the need for improved maternal and child care, hygiene,
      sanitation, and socioeconomic factors.

PMID- 29356770
TI  - Diagnosis and Management of Pediatric Autoimmune Liver Disease: ESPGHAN
      Hepatology Committee Position Statement.
AB  - Paediatric autoimmune liver disease is characterized by inflammatory liver
      histology, circulating autoantibodies, and increased levels of IgG, in the
      absence of a known etiology. Three conditions have a likely autoimmune
      pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis, and
      de novo AIH after liver transplantation. Two types of pediatric AIH are
      recognized according to seropositivity for smooth muscle and/or antinuclear
      antibody (AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type
      1 antibodies (AIH-2).Pertinent issues addressing the diagnosis, treatment, and
      long-term follow-up were formulated by a core group of ESPGHAN members. They have
      commissioned the first authors with execution of this project. Initially, they
      have performed a systematic literature search on MEDLINE, ResearchGate, and
      Mendeley databases during the last 30 years and produced a document focusing on
      prospective and retrospective studies in children. The ESPGHAN core group and
      ESPGHAN Hepatology Committee members voted on each recommendation, using a formal
      voting technique.

PMID- 29356772
TI  - Serial Balloon Dilation to Relieve Gastric Outlet Obstruction Induced by the
      Ingestion of Toilet Cleaner.

PMID- 29356773
TI  - The Third American Society of Regional Anesthesia and Pain Medicine Practice
      Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017.
AB  - The American Society of Regional Anesthesia and Pain Medicine's Third Practice
      Advisory on local anesthetic systemic toxicity is an interim update from its 2010
      advisory. The advisory focuses on new information regarding the mechanisms of
      lipid resuscitation, updated frequency estimates, the preventative role of
      ultrasound guidance, changes to case presentation patterns, and limited
      information related to local infiltration anesthesia and liposomal bupivacaine.
      In addition to emerging information, the advisory updates recommendations
      pertaining to prevention, recognition, and treatment of local anesthetic systemic
      toxicity. WHAT'S NEW IN THIS UPDATE?: This interim update summarizes recent
      scientific findings that have enhanced our understanding of the mechanisms that
      lead to lipid emulsion reversal of LAST, including rapid partitioning, direct
      inotropy, and post-conditioning. Since the previous practice advisory,
      epidemiological data have emerged that suggest a lower frequency of LAST as
      reported by single institutions and some registries, nevertheless a considerable
      number of events still occur within the general community. Contemporary case
      reports suggest a trend toward delayed presentation, which may mirror the
      increased use of ultrasound guidance (fewer intravascular injections), local
      infiltration techniques (slower systemic uptake), and continuous local anesthetic
      infusions. Small patient size and sarcopenia are additional factors that increase
      potential risk for LAST. An increasing number of reported events occur outside of
      the traditional hospital setting and involve non-anesthesiologists.

PMID- 29356774
TI  - The Mechanisms Underlying Lipid Resuscitation Therapy.
AB  - The experimental use of lipid emulsion for local anesthetic toxicity was
      originally identified in 1998. It was then translated to clinical practice in
      2006 and expanded to drugs other than local anesthetics in 2008. Our
      understanding of lipid resuscitation therapy has progressed considerably since
      the previous update from the American Society of Regional Anesthesia and Pain
      Medicine, and the scientific evidence has coalesced around specific discrete
      mechanisms. Intravenous lipid emulsion therapy provides a multimodal
      resuscitation benefit that includes both scavenging (eg, the lipid shuttle) and
      nonscavenging components. The intravascular lipid compartment scavenges drug from
      organs susceptible to toxicity and accelerates redistribution to organs where
      drug (eg, bupivacaine) is stored, detoxified, and later excreted. In addition,
      lipid exerts nonscavenging effects that include postconditioning (via activation
      of prosurvival kinases) along with cardiotonic and vasoconstrictive benefits.
      These effects protect tissue from ischemic damage and increase tissue perfusion
      during recovery from toxicity. Other mechanisms have diminished in favor based on
      lack of evidence; these include direct effects on channel currents (eg, calcium)
      and mass-effect overpowering a block in mitochondrial metabolism. In this
      narrative review, we discuss these proposed mechanisms and address questions left
      to answer in the field. Further work is needed, but the field has made
      considerable strides towards understanding the mechanisms.

PMID- 29356775
TI  - The American Society of Regional Anesthesia and Pain Medicine Checklist for
      Managing Local Anesthetic Systemic Toxicity: 2017 Version.
AB  - The American Society of Regional Anesthesia and Pain Medicine (ASRA) periodically
      revises and updates its checklist for the management of local anesthetic systemic
      toxicity. The 2017 update replaces the 2012 version and reflects new information
      contained in the third ASRA Practice Advisory on Local Anesthetic Systemic
      Toxicity. Electronic copies of the ASRA checklist can be downloaded from the ASRA
      Web site (www.asra.com) for inclusion in local anesthetic toxicity rescue kits or
      perioperative checklist repositories.

PMID- 29356776
TI  - Ultrasound-Assisted Paramedian Thoracic Epidural.

PMID- 29356777
TI  - Reply to Dr Yu et al.

PMID- 29356778
TI  - An Alternate Approach to the Entrapped Transradial Catheter.

PMID- 29356779
TI  - Reply to Dr Grocott.

PMID- 29356780
TI  - The Effect of Infraclavicular Brachial Plexus Blocks on the Axillary Nerve.

PMID- 29356781
TI  - Clinical Characteristics and Associated Systemic Diseases in Patients With
      Esophageal "Absent Contractility"-A Clinical Algorithm.
AB  - GOALS: This study was carried out to assess the clinical characteristics and
      associated systemic diseases seen in patients diagnosed with absent contractility
      as per the Chicago Classification version 3.0, allowing us to propose a
      diagnostic algorithm for their etiologic testing. BACKGROUND: The Chicago
      Classification version 3.0 has redefined major and minor esophageal motility
      disorders using high-resolution esophageal manometry. There is a dearth of
      publications based on research on absent contractility, which historically has
      been associated with myopathic processes such as systemic sclerosis (SSc). STUDY:
      We conducted a retrospective, multicenter study. Data of patients diagnosed with
      absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January
      2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to
      July 2016) and included: age, gender, associated medical conditions, surgical
      history, medications, and specific antibody testing. RESULTS: A total of 207
      patients, including 57 male individuals and 150 female individuals, with mean age
      of 56.1 and 60.0 years, respectively, were included. Disease distribution was as
      follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic
      lupus erythematosus17, Sjogren syndrome 4, polymyositis 3, and dermatomyositis 3.
      Various other etiologies including gastroesophageal reflux disease, postradiation
      esophagitis, neuromuscular disorders, and surgical complications were seen in the
      remaining cohort. CONCLUSIONS: Most practitioners use the term "absent
      contractility" interchangeably with "scleroderma esophagus"; however, only 63% of
      patients with absent contractility had SSc. Overall, 20% had another systemic
      autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for
      absent contractility. Therefore, alternate diagnosis must be sought in these
      patients. We propose an algorithm for their etiologic evaluation.

PMID- 29356782
TI  - A Model for Adaptive Decision Making of "Ablate-and-Wait" Versus Transplantation
      in Patients With Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: In patients with early-stage hepatocellular carcinoma (HCC),
      selection of candidates for liver transplantation (LT) requires refinement based
      on tumor biology to maximize the outcome. We aimed to prognosticate LT candidates
      with HCC using a risk prediction model for post-LT recurrence. PATIENTS AND
      METHODS: A total of 197 consecutive patients were included who underwent LT for
      hepatitis B-related HCC within the Milan criteria. A risk prediction model was
      developed for post-LT recurrence using the Cox model and was internally
      validated. RESULTS: Among those undergoing LT as their first HCC treatment (n=70,
      initial LT group), poor prognosis was associated with maximal tumor size and
      multinodularity. The remaining 127 patients (deferred LT group) received
      radiofrequency ablation (n=69) and/or transarterial chemoembolization (n=98)
      before LT. Multinodularity, maximal tumor size, posttransarterial
      chemoembolization progressive disease, baseline alpha-fetoprotein, and alpha
      fetoprotein difference (between baseline and pre-LT) were incorporated into a
      risk prediction model for the deferred LT group, which was thereby stratified
      into low-risk (score<5), intermediate-risk, and high-risk (score>=8) subgroups.
      Recurrence-free survival was significantly different among the deferred LT
      prognostic subgroups (P<0.001). CONCLUSIONS: This risk prediction model may help
      refinement of "ablate-and-wait" strategy for LT candidates by avoiding LT in
      those with either high risk score at baseline or increasing score under repeated
      locoregional therapies.

PMID- 29356783
TI  - Hypoalbuminemia is Associated With Significantly Higher Liver Transplant Waitlist
      Mortality and Lower Probability of Receiving Liver Transplant.
AB  - GOALS: To evaluate the predictive value of hypoalbuminemia on liver transplant
      (LT) waitlist survival and probability of receiving LT among adults with end
      stage liver disease (ESLD). BACKGROUND: Growing evidence reports on the negative
      prognostic value of hypoalbuminemia among ESLD patients awaiting LT. METHODS:
      Using 2003 to 2015 United Network for Organ Sharing data, we retrospectively
      evaluated the impact of mild-moderate (2.5 to 3.4 g/dL) and severe
      hypoalbuminemia (<2.5 g/dL) on waitlist survival and probability of receiving LT
      among US adults awaiting LT. Outcomes were stratified by liver disease etiology
      and presence of hepatocellular carcinoma (HCC), and evaluated using Kaplan-Meier
      and multivariate Cox proportional hazards models. RESULTS: Among 128,450 adults
      listed for LT, 27.1% had normal albumin (>=3.5 g/dL), 53.7% mild-moderate
      hypoalbuminemia (2.5 to 3.4 g/dL), and 19.2% severe hypoalbuminemia (<2.5 g/dL)
      at time of listing. Patients with severe hypoalbuminemia had significantly lower
      1-year waitlist survival compared with those with normal albumin (80.4% vs.
      95.2%; P<0.001). On multivariate regression, severity of hypoalbuminemia was
      associated with increasing waitlist mortality, even after correcting for model
      for end stage liver disease-sodium and HCC [albumin, 2.5 to 3.4 g/dL: hazard
      ratio (HR), 1.81; 95% confidence interval (CI), 1.62-2.01; P<0.001; <2.5 g/dL:
      HR, 2.46; 95% CI, 2.20-2.76; P<0.001]. Patients with hypoalbuminemia had
      significantly lower probability of receiving LT compared with those with normal
      albumin (albumin <2.5 g/dL: HR, 0.80; 95% CI, 0.78-0.83; P<0.001). CONCLUSIONS:
      ESLD patients with hypoalbuminemia have lower probability of LT despite
      significantly higher waitlist mortality compared with patients with normal
      albumin. If validated by further studies, incorporation of albumin into
      prognostication systems may improve the performance of US donor organ allocation
      systems.

PMID- 29356785
TI  - Impact of Computed Tomography Evaluation Before Colonoscopy for the Management of
      Colonic Diverticular Hemorrhage.
AB  - GOALS: The purpose of this study was to investigate and summarize our experience
      of a standardized strategy using computed tomography (CT) followed by colonoscopy
      for the assessment of colonic diverticular hemorrhage with focus on a comparison
      of CT and colonoscopy findings in patients with colonic diverticular hemorrhage.
      BACKGROUND: Colonic diverticular hemorrhage is usually diagnosed by colonoscopy,
      but it is difficult to identify the responsible bleeding point among many
      diverticula. STUDY: We retrospectively included 257 consecutive patients with
      colonic diverticular hemorrhage. All patients underwent a CT examination before
      colonoscopy. All-cause mortality and rebleeding-free rate after discharge were
      analyzed by Kaplan-Meier analysis and compared using the log-rank test. RESULTS:
      In CT examinations, 184 patients (71.6%) had definite diverticular hemorrhage
      with 31.9% showing intraluminal high-density fluid on plain CT, 39.7% showing
      extravasation, and 31.1% showing arteriovenous increase of extravasation on
      enhanced CT. In colonoscopy, 130 patients (50.6%) showed endoscopic stigmata of
      bleeding with 12.1% showing active bleeding, 17.1% showing a nonbleeding visible
      vessel, and 21.4% showing an adherent clot. A comparison of the locations of
      bleeding in CT and colonoscopy showed that the agreement rate was 67.3%, and the
      disagreement rate was 0.8% when the lesion was identified by both modalities
      patients with definite diverticular hemorrhage identified by CT had a longer
      hospital stay, higher incidences of hemodynamic instability and rebleeding events
      than did patients with presumptive diverticular hemorrhage. CONCLUSION: CT
      evaluation before colonoscopy can be a good option for managing patients with
      colonic diverticular hemorrhage.

PMID- 29356784
TI  - Gastroesophageal Reflux Frequency, Severity, Age of Onset, Family History and
      Acid Suppressive Therapy Predict Barrett Esophagus in a Large Population.
AB  - GOALS: To identify risk factors associated with Barrett esophagus (BE) for
      potential improved surveillance and risk reduction. BACKGROUND: Gastroesophageal
      reflux disease (GERD) is a known risk factor for esophageal adenocarcinoma, but
      the ability of GERD symptom frequency and severity to predict presence of its
      putative precursor lesion, BE, is less well-defined in large, community-based
      populations. STUDY: We conducted a case-control study within the Kaiser
      Permanente Northern California population. Cases had new diagnoses of BE. To
      identify risk factors in the general population, we contrasted cases with
      population controls; to identify risk factors only among patients with GERD, we
      contrasted cases with GERD patients who lacked BE. RESULTS: We interviewed 953
      patients; 320 patients with BE, 316 patients with GERD who lacked BE and 317
      population controls. Compared with population controls, BE risk was highest among
      patients with the most frequent and severe GERD symptoms [odds ratio (OR), 27.00;
      95% confidence interval (CI), 14.52-50.21], nocturnal symptoms (OR, 5.40; 95% CI,
      3.81-7.72), and family history of GERD (OR, 2.55; 95% CI, 1.80-3.62) or BE (OR,
      10.08; 95% CI, 2.83-35.84). Although at least weekly proton pump inhibitor (PPI)
      use was a risk factor for BE (OR, 9.85; 95% CI, 6.54-14.84), among PPI users in
      the general population, GERD symptoms were not strongly associated with the risk
      of BE. Compared with GERD controls, cases were more likely to have onset of GERD
      symptoms before 30 years of age (OR, 1.93; 95% CI, 1.15-3.22) and a family
      history of BE (OR, 3.64; 95% CI, 1.50-8.83). CONCLUSIONS: Severe and frequent
      GERD symptoms are strongly associated with increased risk of BE in the general
      population, especially in the absence of frequent PPI use. Among people with
      GERD, family history of BE and early age of symptom onset were stronger
      predictors of BE. These findings may improve identification of patients at
      highest risk for BE.

PMID- 29356786
TI  - Outcomes Associated With Timing of ERCP in Acute Cholangitis Secondary to
      Choledocholithiasis.
AB  - GOALS: To determine the outcomes associated with timing of endoscopic retrograde
      cholangiopancreatography (ERCP) in patients with acute cholangitis due to
      choledocholithiasis, from a population-based study. BACKGROUND: Although ERCP is
      the cornerstone in the management of patients with acute cholangitis due to
      choledocholithiasis, the effect of timing of ERCP on health care outcomes is not
      well known. MATERIALS AND METHODS: In this retrospective study, national
      inpatient sample (NIS) data were used to identify patients with a combined
      primary or secondary diagnosis of cholangitis and choledocholithiasis from 1998
      to 2012. Patients were divided into 4 groups based on timing of ERCP after
      admission: (1) ERCP performed within 24 hours (urgent ERCP); (2) ERCP performed
      between 24 and 48 hours (early ERCP); (3) ERCP performed after 48 hours (delayed
      ERCP); and (4) no ERCP performed. Main outcomes measured were length of stay
      (LOS), hospitalization charges, and in-hospital mortality. RESULTS: A total of
      107,253 patients were identified of which 77,323 patients underwent ERCP at any
      point in time. Urgent ERCP group had shortest LOS, while delayed ERCP group had
      significantly longer LOS than all other groups (P<0.001). Delayed ERCP group had
      also the highest costs (P<0.001). In-hospital mortality was highest in no ERCP
      group, followed by delayed ERCP group (P<0.001); there was no difference in
      mortality between urgent ERCP and early ERCP. CONCLUSIONS: This study provides
      robust, population-based evidence that ERCP should not be delayed for >48 hours
      in patients with acute cholangitis due to choledocholithiasis.

PMID- 29356787
TI  - Prolonged Recurrent Abdominal Pain is Associated With Ongoing Underlying Mucosal
      Inflammation in Patients who had an Episode of Acute Complicated Diverticulitis.
AB  - BACKGROUND: Recent data suggest continuous chronic inflammation in patients after
      an acute diverticulitis (AD) episode. GOALS: The aim of this article was to
      compare clinical parameters, inflammatory cytokine expression, and immune-cell
      infiltrates between patients after severe versus nonsevere AD, as defined by
      radiology examination during the acute episode. STUDY: Sixteen patients, after
      suffering an episode of AD, were included, and, of them, 8 had severe disease.
      Demographic data, disease characteristics, and inflammatory markers were
      collected. Tissue samples from diverticular and unaffected tissue were obtained
      during colonoscopy. Mucosal inflammation was assessed histologically and by
      measuring inflammatory cytokine mRNA expression. RESULTS: Clinically, continued
      nonspecific abdominal symptoms were significantly more prevalent among patients
      after severe AD compared with patients after nonsevere AD (P=0.0002). Patients
      after severe AD also had significantly higher C reactive protein levels (9.85+/
      7.5 vs. 3+/-2.1 mg/dL; P=0.027) and tendency for higher calprotectin levels
      (115.7+/-85 vs. 35+/-8.7 mg/g; P=0.08). Reverse transcription polymerase chain
      reaction-determined cytokines levels were 5.4+/-4.4, 5.14+/-10, and 0.8+/-0.82
      for tumor necrosis factor alpha, interleukin-6, and interleukin-1beta,
      respectively, in affected mucosa compared with 1.06+/-1.57, 1.56+/-2.1, and
      0.35+/-0.5, respectively, in nonaffected mucosa (P=0.01, 0.05, 0.14,
      respectively). Cytokine expression in patients after nonsevere AD did not differ
      significantly between affected and nonaffected mucosa. Histologic scores for
      crypt distortion, lymphoid aggregates, and lymphocyte infiltration were all
      significantly higher in patients after severe AD compared with patients after
      nonsevere AD (P<0.05 for all comparisons). CONCLUSIONS: Patients after severe AD
      have more prolonged chronic symptoms, higher inflammatory markers, higher tissue
      inflammatory cytokine levels, and more inflammatory infiltrates in diverticular
      colonic tissue than patients after nonsevere AD. These results may contribute to
      patients' risk stratification and guide therapeutic decisions.

PMID- 29356788
TI  - Throat Clearing, Frequently Reported, But is it GERD Related?
AB  - GOALS: To identify the association of throat clearing (TC) with gastroesophageal
      reflux disease (GERD) during objective reflux monitoring in a large number of
      patients studied in our esophageal testing laboratory. BACKGROUND: TC is
      frequently reported and considered to be an atypical symptom of GERD. Atypical
      GERD symptoms have been widely investigated and empirically treated with proton
      pump inhibitors. STUDY: We reviewed ambulatory impedance-pH studies of 186
      patients referred for evaluation of possible GERD from January 2011 to December
      2015 to evaluate the symptom association (SA) of TC with both an abnormal number
      of reflux episodes and also abnormal esophageal acid exposure (EAE). Patients
      were divided into 2 groups; group 1: TC is the only reported symptom, group 2: TC
      is one of the symptoms. All patients were studied off proton pump inhibitors
      therapy. RESULTS: Group 1 where TC was the only symptom in 27/186 (14.5%)
      patients. There was no significant difference in positive SA between this group
      (6/27; 22%) and group 2 (43/159; 27%) (Z score P=0.59). There was also no
      significant association between SA and abnormal EAE whether TC was the only
      presenting symptom (chi, P=0.7) or one of the reported symptoms (chi, P=0.10).
      None of the 6/27 had abnormal EAE. CONCLUSION: Although TC is often considered a
      possible GERD-related symptom, we found a low probability of objective
      association. TC is not likely to be the only presenting symptom, and if it
      happens, it is unlikely to be associated with GERD. Perhaps, TC should not be
      considered as a GERD symptom, even as an atypical one.

PMID- 29356789
TI  - Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed
      cell death-1 (pembrolizumab) for melanoma brain metastases.
AB  - Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line
      treatment for patients with metastatic BRAF wild-type melanoma, alone or combined
      with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and
      the outcomes of patients treated with the anti-PD1 monoclonal antibodies,
      pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS),
      for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all
      patients with MBM treated with PB combined with SRS between 2012 and 2015. The
      primary endpoint was neurotoxicity. The secondary endpoints were local, distant
      intracranial controls and overall survival (OS). Among 74 patients with MBM
      treated with SRS, 25 patients with a total of 58 MBM treated with PB combined
      with SRS within 6 months were included. Radiation necrosis, occurring within a
      median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No
      other significant SRS-related adverse event was observed. After a median follow
      up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%)
      patients. Perilesional oedema and intratumour haemorrhage appearing or increasing
      after SRS were associated with local progression (P<0.001). The median OS was
      15.3 months (95% confidence interval: 4.6-26). The timing between SRS and PB
      administration did not seem to influence the risk of radiation necrosis,
      intracranial control or OS. SRS combined with PB was well tolerated and achieved
      local control in 80% of the lesions. Prolonged OS was observed compared with that
      currently yielded in this population of patients. Prospective studies are
      required to explore further the optimal ways to combine immunotherapy and SRS.

PMID- 29356790
TI  - Clinical and radiological response of BRAF inhibition and MEK inhibition in
      patients with brain metastases from BRAF-mutated melanoma.
AB  - Patients with brain metastases (BM) from melanoma have an overall survival (OS)
      of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an
      effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent
      studies indicate intracranial responses of TT in patients with BM. We analyzed
      146 patients with BM from BRAF-mutated melanoma treated with vemurafenib,
      dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined
      clinical and radiological response, progression-free survival (PFS), and OS.
      Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30;
      95% confidence interval (CI): 6.8-15.7], 8.8 months for dabrafenib alone (n=31;
      95% CI: 3.9-13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6-6.8). A
      significantly longer OS was observed in the dabrafenib+trametinib group than in
      the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30-0.89; P=0.02).
      Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS
      for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2-8.5),
      5.7 months (95% CI: 3.0-8.4) for dabrafenib, and 3.6 months (95% CI: 3.5-3.8) for
      vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM.
      Intracranial disease control rate at 8 weeks in these patients was 65 versus 70%
      extracranially. Neurological symptoms improved in 46% of patients with
      symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with
      BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was
      significantly longer than for vemurafenib. Improvement of neurological symptoms
      was seen in almost half of the patients with symptomatic BM treated with TT.

PMID- 29356791
TI  - Success of rechallenging dabrafenib and trametinib combination therapy after
      trametinib-induced rhabdomyolysis: a case report.
AB  - The mitogen-activated protein kinase pathway regulates cell growth and
      differentiation and is activated by BRAF mutations. BRAF mutations are present in
      about 40-50% of cutaneous melanomas. More than 90% of BRAF mutations are the
      V600E type. BRAF inhibitor (dabrafenib or vemurafenib) and MEK inhibitor
      (trametinib or cobimetinib) combination therapies are effective for BRAF-mutant
      advanced melanomas. A variety of side effects have been observed with combination
      therapy including pyrexia, fatigue, nausea, and vomiting. Rhabdomyolysis is one
      of the most severe adverse events, but it is very rare. Only two cases of
      rhabdomyolysis have been reported in clinical trials. A 41-year-old Japanese
      woman with cutaneous melanoma was started on a combination of dabrafenib and
      trametinib therapy after failure of immune checkpoint therapy. One month later,
      she complained of myalgia and fatigue and was shifted to our hospital. She was
      diagnosed with trametinib-induced rhabdomyolysis and showed improvement only with
      a high volume of fluid infusion. We stopped combination therapy, but there were
      no useful treatment options for her. After resuming dabrafenib, followed by
      trametinib, she did not have any problems. This is the first case of a patient
      with metastatic cutaneous melanoma who could recommence combination therapy after
      trametinib-associated rhabdomyolysis. We assume that not all patients experience
      recurrence of rhabdomyolysis in trametinib-induced rhabdomyolysis. As few cases
      have been reported, more information is needed. We have to evaluate safety
      carefully if rechallenging combination therapy.

PMID- 29356792
TI  - MRI is Better Than CT Scan for Detection of Structural Pathologies After
      Traumatic Posterior Hip Dislocations in Children and Adolescents.
AB  - BACKGROUND: Traumatic posterior hip dislocations in children and adolescents
      requires emergent closed reduction. Postreduction imaging is necessary to assess
      the concentricity of reduction and structural injuries to the hip. There is no a
      consensus for which imaging is a modality of choice in such condition. The
      purposes of this study are to describe magnetic resonance imaging (MRI) findings
      of traumatic posterior hip dislocations and to compare the effectiveness of MRI
      with computerized tomography (CT) in detecting structural abnormalities of the
      hip that impact patient management. METHODS: This study is a retrospective review
      of imaging in traumatically dislocated hips in patients who were treated at our
      institution. All CT and MRI imaging were reviewed and specific osseous and soft
      tissue injuries documented by consensus among 2 musculoskeletal pediatric
      radiologists who interpreted the MRI and CT scans of each patient in a blinded
      manner. RESULTS: In total, 27 patients (23 males, 4 females) with mean age of
      12.5 years (range, 2 to 19 y) with postreduction MRI were evaluated. MRI findings
      revealed femoral head injuries in 17 (62.9%), posterior labral entrapments in 6
      (22.2%), posterior labral tears in 17 (62.9%), posterior wall fractures in 15
      (55.5%), fracture of the posterior unossified part of acetabulum in 4 (14.8%),
      and ligamentum teres injuries in 8 (29.6%). Of 16 patients who had postreduction
      CT scans, 6 (37.5%) had femoral head fractures, 9 (56.3%) had posterior wall
      fractures, and 8 (50%) had intra-articular osseous entrapments. All bony
      fractures and intra-articular entrapment could be seen on MRI imaging. In 16
      patients with both CT and MRI, posterior acetabular injury was detected in 10/16
      (62.5%) on MRI and 9/16 (56.3%) on CT. Three patients with entrapment of labrums
      identified on MRI could not be seen on CT scan. One patient with persistently
      unstable hip after reduction had an entrapped unossified portion of acetabular
      fracture which was seen on MRI but not on CT. CONCLUSIONS: MRI is superior to CT
      scan for detection of structural injuries in children and adolescents with
      traumatic hip dislocation. The unique structural injuries included entrapment of
      posterior labrum and posterior unossified acetabular fractures could be seen only
      at MRI. These findings will impact surgical decision making of these injuries.
      LEVEL OF EVIDENCE: Level IV.

PMID- 29356793
TI  - Fracture Patterns Differ Between Osteogenesis Imperfecta and Routine Pediatric
      Fractures.
AB  - BACKGROUND: It is important to estimate the likelihood that a pediatric fracture
      is caused by osteogenesis imperfecta (OI), especially the least severe type of OI
      (type 1). METHODS: We reviewed records of 29,101 pediatric patients with
      fractures from 2003 through 2015. We included patients with closed fractures not
      resulting from motor vehicle accidents, gunshot wounds, nonaccidental trauma, or
      bone lesions. Patients with OI of any type were identified through International
      Classification of Diseases-9 code. We randomly sampled 500 pediatric patients in
      whom OI was not diagnosed to obtain a control (non-OI) group. We reviewed age at
      time of fracture, sex, fracture type, laterality, and bone and bone region
      fractured. Bisphosphonate use and OI type were documented for OI patients.
      Subanalysis of patients with type-1 OI was performed. The Fisher exact and chi
      tests were used to compare fracture rates between groups. P<0.05 was considered
      significant. Positive likelihood ratios for OI were calculated by fracture
      pattern. RESULTS: The non-OI group consisted of 500 patients with 652 fractures.
      The OI group consisted of 52 patients with 209 fractures. Non-OI patients were
      older at the time of fracture (mean, 9.0+/-5.0 y) than OI patients (mean, 5.5+/
      4.4 y) (P<0.001). OI patients had more oblique, transverse, diaphyseal, and
      bilateral long-bone fractures than non-OI patients (all P<0.001). Non-OI patients
      had more buckle (P=0.013), metaphyseal (P<0.001), and physeal (P<0.001) fractures
      than OI patients. For patients with type-1 OI and long-bone fractures (n=18),
      rates of transverse and buckle fractures were similar compared with controls.
      Transverse humerus (15.2), olecranon (13.8), and diaphyseal humerus (13.0)
      fractures had the highest positive likelihood ratios for OI, and physeal (0.09)
      and supracondylar humerus (0.1) fractures had the lowest. CONCLUSIONS: Transverse
      and diaphyseal humerus and olecranon fractures were most likely to indicate OI.
      Physeal and supracondylar humerus fractures were least likely to indicate OI.
      Radiographic fracture pattern is useful for estimating likelihood of OI. LEVEL OF
      EVIDENCE: Level III.

PMID- 29356794
TI  - Can Computed Tomography Accurately Measure Acetabular Anterversion in
      Developmental Dysplasia of the Hip? Verification and Characterization Using 3D
      Printing Technology.
AB  - BACKGROUND: One of the important pathologic changes in developmental dysplasia of
      the hip (DDH) is increased acetabular version angle (AA). Reasonable correction
      for excessive AA is an important step in the treatment of DDH, making accurate AA
      measurement very crucial. However, the results of different AA measurement
      methods vary. Thus, this study aimed to compare the difference in AA measurements
      between 2-dimensional computed tomography (2D-CT) and 3-dimensional computed
      tomography (3D-CT) in children with DDH and to identify the AA degree in children
      with DDH to guide treatment. METHODS: AA was measured by 2D-CT and 3D-CT in 186
      children with DDH, and the measurement results were compared with the physical
      measurement result in the 3D-printed pelvis (3D-PP) model. The 3D-PP was a 1:1
      model identical to the human pelvis. All patients were unilaterally affected.
      RESULTS: The results of AA measurement through 2D-CT, 3D-CT, and 3D-PP of normal
      hips were 14.0+/-6.6, 11.9+/-5.3, and 11.9+/-3.4 degrees, respectively, whereas
      those of the dislocated hips were 24.9+/-8.9, 19.8+/-5.2, and 19.5+/-4.3 degrees,
      respectively. In both the normal and dislocated hip groups, the results between
      2D-CT and 3D-CT was significantly different (P<0.05), but there was no difference
      between the results of 3D-CT and 3D-PP (P>0.05). The AA of the normal and
      dislocated hips as measured by 3D-PP was 11.9+/-3.6 and 19.6+/-4.3 degrees,
      respectively, with statistically significant difference (P<0.05). In the
      dislocated hips, a significant positive correlation was found between age and AA
      (r=0.756, P<0.05) and between AA and degree of dislocation (r=0.837, P<0.05).
      CONCLUSIONS: 3D-CT is more accurate than 2D-CT for AA measurement, and compared
      with normal hips, AA in dislocated hips increased by ~7.7 degrees on average. AA
      increases as age and degree of dislocation increase. LEVEL OF EVIDENCE: Level II.

PMID- 29356795
TI  - Risk Factors for Prolonged Postoperative Opioid Use After Spinal Fusion for
      Adolescent Idiopathic Scoliosis.
AB  - BACKGROUND: Opioids are commonly used after posterior spinal instrumented fusion
      (PSIF) for adolescent idiopathic scoliosis (AIS). Prescription opioids use can
      potentially lead to misuse, abuse, dependence, and overdose death. Prolonged
      opioid use has not been extensively studied in the postoperative AIS population.
      The purpose of this study is to identify risk factors associated with prolonged
      opioid use after PSIF for AIS. METHODS: A large insurance database was queried
      for AIS patients undergoing PSIF. Patients with prolonged postoperative opioid
      use were defined as those receiving new prescriptions for an opioid medication >6
      weeks following the date of surgery, up to 8 months postoperatively. Preoperative
      and intraoperative risk factors for prolonged opioid use were then examined,
      including the number of spinal levels fused, preoperative opioid prescriptions,
      demographic variables, pertinent comorbidities (anxiety, depression, attention
      deficit hyperactivity disorder, and autism) and other preoperative prescriptions
      (anxiolytics, antidepressants, nonopioid analgesics, neuropathic medications, and
      attention deficit hyperactivity disorder medications). Each variable's
      independent risk for prolonged postoperative opioid use was examined utilizing a
      multivariable binomial regression analysis. P<0.05 was considered statistically
      significant. RESULTS: A total of 511 patients were included in the study. Of this
      50 patients (9.78%) were found to have prolonged opioid use following scoliosis
      surgery. Preoperative opioid use (odds ratio, 2.93; P<0.001) was the most
      significant predictor of prolonged postoperative opioid use. In addition, female
      sex, obesity, a preoperative diagnosis of anxiety and a preoperative prescription
      for a muscle relaxer were also significant positive risk factors for prolonged
      postoperative opioid use. Several factors were found to be protective against
      prolonged postoperative opioid use. Fewer total fusion levels, compared with >=13
      levels, had a significantly lower risk of prolonged opioid use. Preoperative
      anxiolytic and antidepressant use were also both negative predictors of prolonged
      opioid use. CONCLUSIONS: Efforts at addressing preoperative opioid use, anxiety,
      obesity, and providing multimodal pain management strategies should be considered
      to reduce additional postoperative opioid prescriptions after PSIF for AIS. LEVEL
      OF EVIDENCE: Level III-retrospective comparative study.

PMID- 29356796
TI  - Correspondence.

PMID- 29356797
TI  - Reply.

PMID- 29356798
TI  - Staged Prone/Supine Fixation of High-Energy Multicolumnar Tibial Plateau
      Fractures: A Multicenter Analysis.
AB  - PURPOSE: We present a surgical strategy to manage multicolumnar tibial plateau
      fracture variants by addressing the predominant posterior fragment employing a
      Lobenhoffer approach in the prone position followed by supine patient
      repositioning for anterolateral column access. DESIGN: Multicenter retrospective
      analysis. SETTING: Three academic Level 1 trauma centers. PATIENTS/METHODS:
      Twenty-eight cases (28 patients/28 knees) met inclusion criteria between 2003 and
      2014. Patient demographic information was retrospectively reviewed with a mean
      follow-up time of 16.6 months (range 12-34 months). Postoperative radiographic
      analysis, physical examination findings, and patient outcome scores from the Knee
      Injury and Osteoarthritis Outcome Score questionnaire were recorded. RESULTS: The
      average time to union was 3.6 months (range 3-9 months). Eighty-two percent of
      patients had satisfactory articular reduction (less than 2 mm articular step
      off). All patients demonstrated satisfactory coronal (medial proximal tibia angle
      87 +/- 5 degrees) and sagittal alignment (posterior proximal tibia angle 9 +/- 4
      degrees). Condylar width averaged 2.2 mm. Twenty percent of cases required
      posterior lateral columnar plating (in addition to posterior medial columnar
      plating), with none of these cases requiring an extensile exposure modification
      (medial gastrocnemius origin detachment) to expose posterior laterally. In 12
      cases, the posterior approach was staged to allow for anterior soft tissue
      recovery before subsequent staged supine positioning and lateral column fixation.
      The knee range of motion averaged 123 degrees (ranged from 2 degrees of extension
      to 125 degrees flexion). The average Knee Injury and Osteoarthritis Outcome Score
      was 78/100 (range 29-95). Eleven percent of the patients in the series developed
      a surgical site infection (n = 3) with 2 requiring formal irrigation and
      debridement. The most common aseptic complication was radiographic posttraumatic
      arthrosis (18%). Clinically, 1 patient eventually required a total knee
      arthroplasty. CONCLUSIONS: High-energy multicolumnar tibial plateau fractures
      with significant posterior articular surface involvement may be predictably
      addressed with prone positioning, exposure, and fixation followed by supine
      repositioning and the inclusion of an anterior approach. This study demonstrates
      excellent postoperative radiographic results and acceptable clinical outcomes
      resulting from the described staged protocol. LEVEL OF EVIDENCE: Therapeutic
      Level IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 29356799
TI  - Rim Plate Augmentation of the Posterolateral Bare Area of the Tibial Plateau
      Using a 3.5-mm Precontoured Locking Compression Plate: A Cadaveric Study.
AB  - OBJECTIVE: To evaluate the effectiveness of an additional rim plate [3.5-mm
      precontoured locking compression plate (LCP)] for stabilizing the posterolateral
      fragment in lateral tibial plateau fractures. METHODS: Standard lateral locking
      plates [either a proximal tibial plate (PTP) or a proximal tibial locking plate
      (PTLP)] were applied to 40 matched pair knees from 20 fresh-frozen cadavers
      followed by the application of a secondary rim plate [variable angle LCP (VALCP)]
      posterior laterally. RESULTS: The mean ratio of supported articular surface in
      the PTP group was 0.692, whereas that in the PTLP group was 0.569. This
      difference was statistically significant (P < 0.001). Additional rim plating with
      a VALCP could only be performed for 27 of 40 knees; 8 of 20 knees in the PTP
      group and 5 of 20 knees in the PTLP group could not be fitted with a VALCP due to
      anatomic limitations. For the total standard plating group alone, the mean ratio
      of supported articular surface was 0.596, whereas the mean ratio of supported
      articular surface with additional rim plating was 0.798 (P < 0.001). In contrast,
      additional rim plating was possible for more knees that received a PTLP than a
      PTP. Ultimately, there was no significant difference in the ratio of supported
      articular surface after additional rim plating between the 2 different types of
      standard plates (P = 0.087). CONCLUSION: Our results identified a bare area in
      the posterolateral corner of the lateral plateau that was unsupported by rafting
      screws following conventional, 3.5-mm, precontoured LCP plating. Thus, additional
      rim plating may be useful for treating plateau fractures with a posterolateral
      fragment.

PMID- 29356800
TI  - Opioid Use Disorders Are Associated With Perioperative Morbidity and Mortality in
      the Hip Fracture Population.
AB  - OBJECTIVES: To determine whether opioid use disorders (OUDs) are associated with
      adverse perioperative outcomes in patients undergoing surgical fixation for
      proximal femur fractures. METHODS: The National Hospital Discharge Survey was
      queried to identify patients surgically treated for proximal femur fractures
      between 1990 and 2007. Patients were grouped into those with a diagnosis of OUD,
      nonopioid drug use disorder, or neither. Demographic information and
      comorbidities were included in univariable and multivariable analyses to identify
      independent risk factors for perioperative outcomes. RESULTS: A total of 8154
      patients with a diagnosis of drug use disorder and 4704 patients with a diagnosis
      of OUD were identified from a cohort of 4,732,165 surgically treated proximal
      femur fractures. Patients with OUD were significantly younger (46 vs. 79), and a
      significantly smaller proportion of them had medical comorbidities (21.9% vs.
      60.2%) when compared with the no drug misuse cohort. Patients with OUD had
      significantly more medical complications (51.1% vs. 26.8%), mechanical
      complications (3% vs. 0.3%), and adverse events (55% vs. 39.7%) when compared
      with the no drug misuse group. OUD had higher odds for leaving against medical
      advice [odds ratio (OR) 12.868, range 10.7771-15.375], for any adverse event (OR
      4.107, range 3.869-4.360), and for mortality (OR 1.744, range 1.250-2.433) when
      compared with nondrug misusers. CONCLUSIONS: Despite being younger and with
      significantly less medical comorbidities, patients with OUD have higher odds for
      adverse events, leaving against medical advice, and mortality after surgical
      treatment of a hip fracture. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29356801
TI  - Effect of Blocking Screws on Union of Infraisthmal Femur Fractures Stabilized
      With a Retrograde Intramedullary Nail.
AB  - OBJECTIVE: To investigate the effect of blocking screws (BS) on the union rate
      and stability of infraisthmal femur fractures treated with retrograde
      intramedullary nail (RIMN) insertion. DESIGN: Retrospective cohort study.
      SETTING: A single level 1 trauma center. PATIENTS/PARTICIPANTS: All patients with
      an infraisthmal femur fracture treated with a RIMN from 2005 to 2012 were
      included. INTERVENTION: All fractures were treated with a RIMN. BS were used at
      the discretion of the treating surgeon. MAIN OUTCOME MEASUREMENTS: (1)
      Radiographic time to union, (2) initial postoperative sagittal and coronal
      angulation, and (3) final sagittal and coronal angulation. RESULTS: Neither the
      average time to union (BS 21.1 weeks vs. 21.8 weeks), nor union rates (BS 61% vs.
      77%) were statistically different between BS and non-BS constructs. No
      significant alignment differences existed whether BS were used or not.
      CONCLUSIONS: In this study, we were not able to verify our hypothesis. In fact,
      we did not find any significant advantages when BS were added to a RIMN construct
      for distal femur fractures with respect to union time, union rate, or
      improvements in alignment. Additional studies are needed to determine the actual
      benefit of BS in the treatment of infraisthmal femoral shaft fractures treated
      with retrograde intramedullary nailing. LEVEL OF EVIDENCE: Therapeutic Level III.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 29356809
TI  - Relevance of Social Networks for Adolescent Obesity.

PMID- 29356802
TI  - 3,5-Dicaffeoylquinic Acid Disperses Aspergillus Fumigatus Biofilm and Enhances
      Fungicidal Efficacy of Voriconazole and Amphotericin B.
AB  - BACKGROUND The aim of this study was to evaluate the dispersal effects of 3,5
      dicaffeoylquinic acid (3,5-DCQA) against the preformed biofilm of Aspergillus
      fumigatus and to investigate its potential mechanism. MATERIAL AND METHODS
      Aspergillus fumigatus biofilms of laboratory strain AF293 and clinical strain
      GXMU04 were generated in 24- or 96-well polystyrene microtiter plates in vitro.
      Crystal violet assay and XTT reduction assay were performed to evaluate the
      effects of 3,5-DCQA on biofilm biomass, extracellular matrix, and metabolic
      activity alteration of cells in biofilms. Real-time PCR was performed to quantify
      the expression of hydrophobin genes. The cytotoxicity of 3,5-DCQA on human
      erythrocytes was evaluated by a hemolytic assay. RESULTS The results indicated
      that 3,5-DCQA in subminimum inhibitory concentrations (256 to 1024 mg/L) elicited
      optimal A. fumigatus biofilm dispersion activity and improved the efficacy of VRC
      and AMB in minimal fungicidal concentrations (MFCs) to combat fungal cells
      embedded in biofilms. The results of scanning electron microscope (SEM) and
      confocal laser scanning microscopy (CLSM) revealed 3,5-DCQA facilitated the entry
      of antifungal agents into the A. fumigatus biofilm through eliminating the
      hydrophobic extracellular matrix (ECM) without affecting fungal growth. Real-time
      PCR indicated that 3,5-DCQA down-regulated the expression of hydrophobin genes.
      Hemolytic assay confirmed that 3,5-DCQA exhibited a low cytotoxicity against
      human erythrocytes. CONCLUSIONS Subminimum inhibitory concentrations of 3,5-DCQA
      can disperse A. fumigatus biofilm and enhance fungicidal efficacy of VRC and AMB
      through down-regulating expression of the hydrophobin genes. The study indicated
      the anti-biofilm potential of 3,5-DCQA for the management of A. fumigatus biofilm
      associated infection.

PMID- 29356810
TI  - Association Between Fluid Balance and Outcomes in Critically Ill Children: A
      Systematic Review and Meta-analysis.
AB  - Importance: After initial resuscitation, critically ill children may accumulate
      fluid and develop fluid overload. Accruing evidence suggests that fluid overload
      contributes to greater complexity of care and worse outcomes. Objective: To
      describe the methods to measure fluid balance, define fluid overload, and
      evaluate the association between fluid balance and outcomes in critically ill
      children. Data Sources: Systematic search of MEDLINE, EMBASE, Cochrane Library,
      trial registries, and selected gray literature from inception to March 2017.
      Study Selection: Studies of children admitted to pediatric intensive care units
      that described fluid balance or fluid overload and reported outcomes of interest
      were included. No language restrictions were applied. Data Extraction and
      Synthesis: All stages were conducted independently by 2 reviewers. Data extracted
      included study characteristics, population, fluid metrics, and outcomes. Risk of
      bias was assessed using the Newcastle-Ottawa Scale. Narrative description of
      fluid assessment methods and fluid overload definitions was done. When feasible,
      pooled analyses were performed using random-effects models. Main Outcomes and
      Measures: Mortality was the primary outcome. Secondary outcomes included
      treatment intensity, organ failure, and resource use. Results: A total of 44
      studies (7507 children) were included in this systematic review and meta
      analysis. Of those, 27 (61%) were retrospective cohort studies, 13 (30%) were
      prospective cohort studies, 3 (7%) were case-control studies, and 1 study (2%)
      was a secondary analysis of a randomized trial. The proportion of children with
      fluid overload varied by case mix and fluid overload definition (median, 33%;
      range, 10%-83%). Fluid overload, however defined, was associated with increased
      in-hospital mortality (17 studies [n = 2853]; odds ratio [OR], 4.34 [95% CI, 3.01
      6.26]; I2 = 61%). Survivors had lower percentage fluid overload than nonsurvivors
      (22 studies [n = 2848]; mean difference, -5.62 [95% CI, -7.28 to -3.97]; I2 =
      76%). After adjustment for illness severity, there was a 6% increase in odds of
      mortality for every 1% increase in percentage fluid overload (11 studies [n =
      3200]; adjusted OR, 1.06 [95% CI, 1.03-1.10]; I2 = 66%). Fluid overload was
      associated with increased risk for prolonged mechanical ventilation (>48 hours)
      (3 studies [n = 631]; OR, 2.14 [95% CI, 1.25-3.66]; I2 = 0%) and acute kidney
      injury (7 studies [n = 1833]; OR, 2.36 [95% CI, 1.27-4.38]; I2 = 78%).
      Conclusions and Relevance: Fluid overload is common and is associated with
      substantial morbidity and mortality in critically ill children. Additional
      research should now ideally focus on interventions aimed to mitigate the
      potential for harm associated with fluid overload.

PMID- 29356811
TI  - Association of Time to Treatment With Short-term Outcomes for Pediatric Patients
      With Refractory Convulsive Status Epilepticus.
AB  - Importance: Treatment delay for seizures can lead to longer seizure duration.
      Whether treatment delay is associated with major adverse outcomes, such as death,
      remains unknown. Objective: To evaluate whether untimely first-line
      benzodiazepine treatment is associated with unfavorable short-term outcomes.
      Design, Setting, and Participants: This multicenter, observational, prospective
      cohort study included 218 pediatric patients admitted between June 1, 2011, and
      July 7, 2016, into the 11 tertiary hospitals in the United States within the
      Pediatric Status Epilepticus Research Group. Patients, ranging in age from 1
      month to 21 years, with refractory convulsive status epilepticus (RCSE) that did
      not stop after the administration of at least 2 antiseizure medications were
      included. Patients were divided into 2 cohorts: those who received the first-line
      benzodiazepine treatment in less than 10 minutes and those who received it 10 or
      more minutes after seizure onset (untimely). Data were collected and analyzed
      from June 1, 2011, to July 7, 2016. Main Outcomes and Measures: The primary
      outcome was death during the related hospital admission. The secondary outcome
      was the need for continuous infusion for seizure termination. Multivariate
      analysis of mortality controlled for structural cause, febrile RCSE, age, and
      previous neurological history (including previous RCSE events). Use of continuous
      infusions was additionally adjusted for generalized RCSE, continuous RCSE, and 5
      or more administrations of antiseizure medication. Results: A total of 218
      patients were included, among whom 116 (53.2%) were male and the median
      (interquartile range) age was 4.0 (1.2-9.6) years. The RCSE started in the
      prehospital setting for 139 patients (63.8%). Seventy-four patients (33.9%)
      received their first-line benzodiazepine treatment in less than 10 minutes, and
      144 (66.1%) received untimely first-line benzodiazepine treatment. Multivariate
      analysis showed that patients who received untimely first-line benzodiazepine
      treatment had higher odds of death (adjusted odds ratio [AOR], 11.0; 95% CI, 1.43
      to infinity; P = .02), had greater odds of receiving continuous infusion (AOR,
      1.8; 95% CI, 1.01-3.36; P = .047), had longer convulsive seizure duration (AOR,
      2.6; 95% CI, 1.38-4.88; P = .003), and had more frequent hypotension (AOR 2.3;
      95% CI, 1.16-4.63; P = .02). In addition, the timing of the first-line
      benzodiazepine treatment was correlated with the timing of the second-line (95%
      CI, 0.64-0.95; P < .001) and third-line antiseizure medications (95% CI, 0.25
      0.78; P < .001). Conclusions and Relevance: Among pediatric patients with RCSE,
      an untimely first-line benzodiazepine treatment is independently associated with
      a higher frequency of death, use of continuous infusions, longer convulsion
      duration, and more frequent hypotension. Results of this study raise the question
      as to whether poor outcomes could, in part, be prevented by earlier
      administration of treatment.

PMID- 29356812
TI  - Comparison of Observed Harms and Expected Mortality Benefit for Persons in the
      Veterans Health Affairs Lung Cancer Screening Demonstration Project.

PMID- 29356813
TI  - Association of Veterans Health Administration Home-Based Programs With Access to
      and Participation in Cardiac Rehabilitation.

PMID- 29356815
TI  - Position matching between the visual fields in strabismus.
AB  - The misalignment of visual input in strabismus disrupts positional judgments. We
      measured positional accuracy in the extrafoveal visual field (1 degrees -7
      degrees  eccentricity) of a large group of strabismic subjects and a normal
      control group to identify positional distortions associated with the direction of
      strabismus. Subjects performed a free localization task in which targets were
      matched in opposite hemifields whilst fixating on a central cross. The constant
      horizontal error of each response was taken as a measure of accuracy, in addition
      to radial and angular error. In monocular conditions, all stimuli were viewed by
      one eye; thus, the error reflected spatial bias. In dichoptic conditions, the
      targets were seen by separate eyes; thus, the error reflected the perceived
      stimulus shift produced by ocular misalignment in addition to spatial bias. In
      both viewing conditions, both groups showed reliable over- and underestimations
      of visual field position, here termed a compression of response coordinates. The
      normal group showed compression in the left periphery, regardless of eye of
      stimulation. The strabismic group showed a visual field-specific compression that
      was clearly associated with direction of strabismus. The variation in perceived
      shift of strabismic subjects was largely accounted for by the biases present in
      monocular viewing, suggesting that binocular correspondence was uniform in the
      tested region. The asymmetric strabismic compression could not be reproduced in
      normal subjects through prism viewing, and its presence across viewing conditions
      suggests a hemifield-specific change in spatial coding induced by long-standing
      ocular misalignment.

PMID- 29356814
TI  - Recentering bias for temporal saccades only: Evidence from binocular recordings
      of eye movements.
AB  - It is well known that the saccadic system presents multiple asymmetries. Notably,
      temporal (as opposed to nasal) saccades, centripetal (as opposed to centrifugal)
      saccades (i.e., the recentering bias) and saccades from the abducting eye (as
      opposed to the concomitant saccades from the adducting eye) exhibit higher peak
      velocities. However, these naso-temporal and centripetal-centrifugal asymmetries
      have always been studied separately. It is thus unknown which asymmetry prevails
      when there is a conflict between both asymmetries, i.e., in case of centripetal
      nasal saccades or centrifugal temporal saccades. This study involved binocular
      recordings of eye movements to examine both the naso-temporal and centripetal
      centrifugal asymmetries so as to determine how they work together. Twenty-eight
      participants had to make saccades toward stimuli presented either centrally or in
      the periphery in binocular conditions. We found that temporal and abducting
      saccades always exhibit higher peak velocities than nasal and adducting saccades,
      irrespective of their centripetal or centrifugal nature. However, we showed that
      the velocity advantage for centripetal saccades is only found for temporal and
      not for nasal saccades. Such a result is of importance as it could provide new
      insights about the physiological origins of the asymmetries found in the saccadic
      system.

PMID- 29356816
TI  - Assessing Social Contagion in Body Mass Index, Overweight, and Obesity Using a
      Natural Experiment.
AB  - Importance: Little is known about whether the substantial clustering of obesity
      and overweight within social and geographic networks results from causal
      pathways, such as social contagion and shared environments, or from self
      selection. Objectives: This study aimed to determine whether exposure to
      communities with higher rates of obesity increases the body mass index (BMI) of
      individuals, calculated as weight in kilograms divided by height in meters
      squared, and their risk of being overweight or obese, and whether social
      contagion, shared environments, or self-selection can account for identified
      differences. Design, Setting, and Participants: This natural experiment study
      used the routine assignment of military service members to installations as a
      source of exogenous variation in exposure to communities with higher vs lower
      rates of obesity. The study, which used data collected by the Military Teenagers'
      Environments, Exercise, and Nutrition Study, examined families from 38 military
      installations around the United States to determine if individuals had higher BMI
      and greater odds of overweight and obesity when assigned to installations in
      counties with higher rates of obesity. The study also examined if the
      relationship persisted after controlling for shared built environments. The
      participants included 1 parent and 1 child aged 12 or 13 years from 1519 families
      of Army-enlisted personnel. Data analysis was completed from November 2016 to
      October 2017. Exposures: Adult obesity rate in the county where the assigned
      installation of the service member was located. Time at installation and location
      of residence (on-installation vs off-installation) were used to measure the
      degree of exposure. Main Outcomes and Measures: For parents, outcomes were BMI,
      overweight/obesity (BMI, >=25) and obesity (BMI, >=30). For children, outcomes
      were BMI z score, overweight/obesity (BMI percentile for age and sex, >=85), and
      obesity (BMI percentile for age and sex, >=95). These outcomes were based on self
      reports for parents, self-reports and parent reports for all children, and
      anthropometric measurements for a subsample of children. Results: Members of 1519
      families participated, including 1314 adults (of whom 740, or 56%, were fathers)
      and 1111 children (of whom 576, or 52%, were boys); anthropometric measurements
      were performed on 458 children. The sample was 40% white, 22% black, 24%
      Hispanic, and 14% other races/ethnicities. A 1-percentage point higher county
      obesity rate was associated with a higher BMI (a difference of 0.08; 95% CI, 0.02
      0.13) and greater odds of obesity (adjusted odds ratio [aOR], 1.05; 95% CI, 1.02
      1.08) in parents, and a higher BMI z score (0.01; 95% CI, 0.003-0.02) and greater
      odds of overweight/obesity (aOR, 1.04; 95% CI, 1.01-1.06) in children. The
      evidence supported stronger associations among families with more time at
      installation and off-installation residence. Associations persisted even after
      controlling for shared built environments. Conclusions and Relevance: Exposure to
      counties with higher rates of obesity was associated with higher BMI and higher
      odds of overweight and/or obesity in parents and children. There was no evidence
      to support self-selection or shared built environments as possible explanations,
      which suggests the presence of social contagion in obesity.

PMID- 29356817
TI  - Ascent to the Summit of the CME Pyramid.

PMID- 29356818
TI  - Evolution of Continuing Medical Education: Promoting Innovation Through
      Regulatory Alignment.

PMID- 29356819
TI  - Reducing Harms in Lung Cancer Screening-Bach to the Future.

PMID- 29356821
TI  - The Federal Right to Try Act of 2017-A Wrong Turn for Access to Investigational
      Drugs and the Path Forward.

PMID- 29356820
TI  - Web Platform vs In-Person Genetic Counselor for Return of Carrier Results From
      Exome Sequencing: A Randomized Clinical Trial.
AB  - Importance: A critical bottleneck in clinical genomics is the mismatch between
      large volumes of results and the availability of knowledgeable professionals to
      return them. Objective: To test whether a web-based platform is noninferior to a
      genetic counselor for educating patients about their carrier results from exome
      sequencing. Design, Setting, and Participants: A randomized noninferiority trial
      conducted in a longitudinal sequencing cohort at the National Institutes of
      Health from February 5, 2014, to December 16, 2016, was used to compare the web
      based platform with a genetic counselor. Among the 571 eligible participants, 1
      to 7 heterozygous variants were identified in genes that cause a phenotype that
      is recessively inherited. Surveys were administered after cohort enrollment,
      immediately following trial education, and 1 month and 6 months later to
      primarily healthy postreproductive participants who expressed interest in
      learning their carrier results. Both intention-to-treat and per-protocol analyses
      were applied. Interventions: A web-based platform that integrated education on
      carrier results with personal test results was designed to directly parallel
      disclosure education by a genetic counselor. The sessions took a mean (SD) time
      of 21 (10.6), and 27 (9.3) minutes, respectively. Main Outcomes and Measures: The
      primary outcomes and noninferiority margins (deltaNI) were knowledge (0 to 8,
      deltaNI = -1), test-specific distress (0 to 30, deltaNI = +1), and decisional
      conflict (15 to 75, deltaNI = +6). Results: After 462 participants (80.9%)
      provided consent and were randomized, all but 3 participants (n = 459) completed
      surveys following education and counseling; 398 (86.1%) completed 1-month surveys
      and 392 (84.8%) completed 6-month surveys. Participants were predominantly well
      educated, non-Hispanic white, married parents; mean (SD) age was 63 (63.1) years
      and 246 (53.6%) were men. The web platform was noninferior to the genetic
      counselor on outcomes assessed at 1 and 6 months: knowledge (mean group
      difference, -0.18; lower limit of 97.5% CI, -0.63; deltaNI = -1), test-specific
      distress (median group difference, 0; upper limit of 97.5% CI, 0; deltaNI = +1),
      and decisional conflict about choosing to learn results (mean group difference,
      1.18; upper limit of 97.5% CI, 2.66; deltaNI = +6). There were no significant
      differences between the genetic counselors and web-based platform detected
      between modes of education delivery in disclosure rates to spouses (151 vs 159;
      relative risk [RR], 1.04; 95% CI, 0.64-1.69; P > .99), children (103 vs 117; RR,
      1.07; 95% CI, 0.85-1.36; P = .59), or siblings (91 vs 78; RR, 1.17; 95% CI, 0.94
      1.46; P = .18). Conclusions and Relevance: This trial demonstrates noninferiority
      of web-based return of carrier results among postreproductive, mostly healthy
      adults. Replication studies among younger and more diverse populations are needed
      to establish generalizability. Yet return of results via a web-based platform may
      be sufficient for subsets of test results, reserving genetic counselors for
      return of results with a greater health threat. Trial Registration:
      clinicaltrials.gov Identifier: NCT00410241.

PMID- 29356824
TI  - Time May Be of the Essence in the Treatment of Pediatric Patients With Refractory
      Convulsive Status Epilepticus.

PMID- 29356822
TI  - The Effective Dynamic Ranges for Glaucomatous Visual Field Progression With
      Standard Automated Perimetry and Stimulus Sizes III and V.
AB  - Purpose: It has been shown that threshold estimates below approximately 20 dB
      have little effect on the ability to detect visual field progression in glaucoma.
      We aimed to compare stimulus size V to stimulus size III, in areas of visual
      damage, to confirm these findings by using (1) a different dataset, (2) different
      techniques of progression analysis, and (3) an analysis to evaluate the effect of
      censoring on mean deviation (MD). Methods: In the Iowa Variability in Perimetry
      Study, 120 glaucoma subjects were tested every 6 months for 4 years with size III
      SITA Standard and size V Full Threshold. Progression was determined with three
      complementary techniques: pointwise linear regression (PLR), permutation of PLR,
      and linear regression of the MD index. All analyses were repeated on "censored''
      datasets in which threshold estimates below a given criterion value were set to
      equal the criterion value. Results: Our analyses confirmed previous observations
      that threshold estimates below 20 dB contribute much less to visual field
      progression than estimates above this range. These findings were broadly similar
      with stimulus sizes III and V. Conclusions: Censoring of threshold values < 20 dB
      has relatively little impact on the rates of visual field progression in patients
      with mild to moderate glaucoma. Size V, which has lower retest variability,
      performs at least as well as size III for longitudinal glaucoma progression
      analysis and appears to have a larger useful dynamic range owing to the upper
      sensitivity limit being higher.

PMID- 29356823
TI  - Association of beta-Amyloid and Apolipoprotein E epsilon4 With Memory Decline in
      Preclinical Alzheimer Disease.
AB  - Importance: Older age, high levels of beta-amyloid (Abeta), and the presence of
      the apolipoprotein E (APOE) epsilon4 allele are risk factors for Alzheimer
      disease (AD). However, the extent to which increasing age, Abeta, and epsilon4
      are associated with memory decline remains unclear, and the age at which memory
      decline begins for Abeta-positive epsilon4 carriers and noncarriers has not been
      determined. Objective: To determine the association of age, Abeta level, and APOE
      epsilon4 with memory decline in a large group of cognitively healthy older
      adults. Design, Setting, and Participants: This longitudinal observational study
      included cognitively healthy older adults (age >60 years) enrolled in the
      Australian Imaging, Biomarkers and Lifestyle (AIBL) study from March 31, 2006,
      through March 31, 2017; of 1583 individuals enrolled, 1136 refused or were
      excluded owing to other criteria (eg, having mild cognitive impairment or AD).
      Participants underwent Abeta imaging in research clinics in Perth and Melbourne
      and more than 72 months of follow-up (at 18-month intervals). The association of
      age with memory was fitted to a quadratic model. Age was treated as a continuous,
      time-dependent variable. Exposures: beta-Amyloid imaging using positron emission
      tomography, genotyping for APOE E4, and longitudinal neuropsychological
      assessments of episodic memory during the 72-month follow-up. Main Outcomes and
      Measures: Episodic memory composite score. Results: Of the 447 participants, 203
      (45.4%) were men and 244 (54.6%) were women; mean (SD) age was 72.5 (6.6) years.
      Equal proportions of female participants were observed in each Abeta-E4 group (24
      of 51 Abeta-positive epsilon4 noncarriers [47.1%] ; 35 of 64 Abeta-negative
      epsilon4 carriers [54.7%]; 40 of 72 Abeta-positive epsilon4 carriers [55.6%]; and
      145 of 260 Abeta-negative epsilon4 noncarriers [55.8%]). Adults with Abeta
      findings (mean [SD] age, 74.4 [6.8] years) were approximately 4 years older than
      those negative for Abeta (mean [SD] age, 69.8 [6.1] years). Memory decline
      diverged significantly from Abeta-negative E4 noncarriers at an earlier age in
      Abeta-positive E4 carriers (64.5 years) than in Abeta-positive E4 noncarriers
      (76.5 years), such that by 85 years of age, Abeta-positive epsilon4 carriers
      performed approximately 1.5 SD units worse on the episodic memory composite than
      Abeta-negative epsilon4 noncarriers and approximately 0.8 SD units worse than
      Abeta-positive epsilon4 noncarriers. Memory performance of Abeta-negative E4
      carriers did not differ from that of the Abeta-negative E4 noncarriers (estimate
      [SE], 0.001 [0.001]; t = 0.526; P = .77). Conclusions and Relevance: Prior work
      has shown that Abeta and epsilon4 combine to influence memory decline in
      nondemented older adults. Results of this study indicate that increasing age may
      further exacerbate these effects. The estimates provided may be used to determine
      the risk of memory decline associated with Abeta and epsilon4 at each age.

PMID- 29356825
TI  - Association of Baseline Statin Use Among Older Adults Without Clinical
      Cardiovascular Disease in the SPRINT Trial.

PMID- 29356826
TI  - Globus Pallidus Interna or Subthalamic Nucleus Deep Brain Stimulation for
      Parkinson Disease: A Review.
AB  - Importance: Selection of the best deep brain stimulation (DBS) target-subthalamic
      nucleus (STN) or globus pallidus interna (GPi)-for treatment of motor
      complications in Parkinson disease remains a matter of debate. Observations:
      Increasing evidence from randomized clinical trials indicates that motor benefit
      is similar between both targets, including an effect on dyskinesia and
      improvement in quality of life. Deep brain stimulation of the STN offers
      consistently greater dopaminergic medication reduction, possible mild benefit in
      nonmotor domains, and potential economic advantage. Deep brain stimulation of the
      GPi provides a probable advantage in dyskinesia suppression, management of
      symptoms with unilateral leads, and flexibility in medications and programming
      adjustments. Overall, STN DBS is at potentially higher or equal risk for
      neuropsychiatric changes compared with GPi DBS. Conclusions and Relevance: Both
      GPi and STN DBS provide similar, consistent, marked motor benefits, but subtle
      target differences exist. Target selection should be tailored to each patient's
      clinical presentation, neuropsychiatric profile, and goals of surgery, allowing
      customization of this therapy and improved individual outcomes.

PMID- 29356828
TI  - Out-of-Pocket Spending and Premium Contributions After Implementation of the
      Affordable Care Act.
AB  - Importance: The Affordable Care Act (ACA) was associated with a reduced number of
      Americans who reported being unable to afford medical care, but changes in actual
      health spending by households are not known. Objectives: To estimate changes in
      household spending on health care nationwide after implementation of the ACA.
      Design, Setting, and Participants: Population-based data from the Medical
      Expenditure Panel Survey from January 1, 2012, through December 31, 2015, and
      multivariable regression were used to examine changes in out-of-pocket spending,
      premium contributions, and total health spending (out-of-pocket plus premiums)
      after the ACA's coverage expansions on January 1, 2014. The study population
      included a nationally representative sample of US adults aged 18 to 64 years (n =
      83 431). In addition, changes were assessed in the likelihood of exceeding
      affordability thresholds for each outcome and spending changes for income
      subgroups defined under the ACA to determine program eligibility at 138% or less,
      139% to 250%, 251% to 400%, and greater than 400% of the federal poverty level
      (FPL). Exposure: Implementation of the ACA's major insurance programs on January
      1, 2014. Main Outcomes and Measures: Mean individual-level out-of-pocket spending
      and premium payments and the percentage of persons experiencing high-burden
      spending, defined as more than 10% of family income for out-of-pocket expenses,
      more than 9.5% for premium payments, and more than 19.5% for out-of-pocket plus
      premium payments. Results: In this nationally representative survey of 83 431
      adults (weighted frequency, 49.1% men and 50.9% women; median age, 40.3 years;
      interquartile range, 28.6-52.4 years), ACA implementation was associated with an
      11.9% decrease (95% CI, -17.1% to -6.4%; P < .001) in mean out-of-pocket spending
      in the full sample, a 21.4% decrease (95% CI, -30.1% to -11.5%; P < .001) in the
      lowest-income group (<=138% of the FPL), an 18.5% decrease (95% CI, -27.0% to 
      9.0%; P < .001) in the low-income group (139%-250% of the FPL), and a 12.8%
      decrease (95% CI, -22.1% to -2.4%; P = .02) in the middle-income group (251%-400%
      of the FPL). Mean premium spending increased in the full sample (12.1%; 95% CI,
      1.9%-23.3%) and the higher-income group (22.9%; 95% CI, 5.5%-43.1%). Combined out
      of-pocket plus premium spending decreased in the lowest-income group only (
      16.0%; 95% CI, -27.6% to -2.6%). The odds of household out-of-pocket spending
      exceeding 10% of family income decreased in the full sample (odds ratio [OR],
      0.80; 95% CI, 0.70-0.90) and in the lowest-income group (OR, 0.80; 95% CI, 0.67
      0.97). The odds of high-burden premium spending increased in the middle-income
      group (OR, 1.28; 95% CI, 1.03-1.59). Conclusions and Relevance: Implementation of
      the ACA was associated with reduced out-of-pocket spending, particularly for low
      income persons. However, many of these individuals continue to experience high
      burden out-of-pocket and premium spending. Repeal or substantial reversal of the
      ACA would especially harm poor and low-income Americans.

PMID- 29356827
TI  - Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain
      Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial.
AB  - Importance: The role of the apolipoprotein E (APOE) epsilon4 allele as an effect
      modifier in lifestyle interventions to prevent cognitive impairment is still
      unclear. Objective: To examine whether the APOE epsilon4 allele modifies the
      previously reported significant cognitive benefits of a multidomain lifestyle
      intervention (prespecified subgroup analysis). Design, Setting, and Participants:
      The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and
      Disability (FINGER) was a randomized clinical trial in 6 centers across Finland
      (screening and randomization performed from September 7, 2009, through November
      24, 2011; intervention duration, 2 years). Data analysis was performed from
      August 1, 2015, to March 31, 2016. The study population was at-risk older
      individuals from the general population. Inclusion criteria were age of 60 to 77
      years; Cardiovascular Risk Factors, Aging, and Dementia risk score of at least 6
      points; and cognition at a mean level or slightly lower than expected for age.
      Individuals with dementia or substantial cognitive impairment and conditions that
      prevented cooperation or safe engagement in the intervention were excluded. APOE
      genotype data were available for 1175 of the 1260 participants. Interventions:
      Participants were randomly assigned in a 1:1 ratio to a multidomain intervention
      group (diet, exercise, cognitive training, and vascular risk management) or a
      control group (general health advice). Group allocation was not actively
      disclosed to participants, and outcome assessors were masked to group allocation.
      Main Outcomes and Measures: Primary outcome was change in cognition measured
      through a comprehensive neuropsychological test battery. Analysis was based on
      modified intention to treat (participants with at least 1 postbaseline
      assessment). Results: A total of 1109 participants (mean [SD] age, 69.3 [4.7]
      years; 514 [46.3%] female) were included in the analysis: 362 APOE epsilon4
      allele carriers (173 intervention and 189 control) and 747 noncarriers (380
      intervention and 367 control). The APOE epsilon4 carriers and noncarriers were
      not significantly different at baseline (except for serum cholesterol level). The
      difference between the intervention and control groups in annual
      neuropsychological test battery total score change was 0.037 (95% CI, 0.001 to
      0.073) among carriers and 0.014 (95% CI, -0.011 to 0.039) among noncarriers.
      Intervention effect was not significantly different between carriers and
      noncarriers (0.023; 95% CI, -0.021 to 0.067). Conclusions and Relevance: Healthy
      lifestyle changes may be beneficial for cognition in older at-risk individuals
      even in the presence of APOE-related genetic susceptibility to dementia. Whether
      such benefits are more pronounced in APOE epsilon4 carriers compared with
      noncarriers should be further investigated. The findings also emphasize the
      importance of early prevention strategies that target multiple modifiable risk
      factors simultaneously. Trial Registration: ClinicalTrials.gov Identifier:
      NCT01041989.

PMID- 29356830
TI  - Informed Consent Training in Pediatrics-Are We Doing Enough?

PMID- 29356831
TI  - ?

PMID- 29356829
TI  - Clinical, Biomarker, and Molecular Delineations and Genotype-Phenotype
      Correlations of Ataxia With Oculomotor Apraxia Type 1.
AB  - Importance: Ataxia with oculomotor apraxia type 1 (AOA1) is an autosomal
      recessive cerebellar ataxia due to mutations in the aprataxin gene (APTX) that is
      characterized by early-onset cerebellar ataxia, oculomotor apraxia, axonal motor
      neuropathy, and eventual decrease of albumin serum levels. Objectives: To improve
      the clinical, biomarker, and molecular delineation of AOA1 and provide genotype
      phenotype correlations. Design, Setting, and Participants: This retrospective
      analysis included the clinical, biological (especially regarding biomarkers of
      the disease), electrophysiologic, imaging, and molecular data of all patients
      consecutively diagnosed with AOA1 in a single genetics laboratory from January 1,
      2002, through December 31, 2014. Data were analyzed from January 1, 2015, through
      January 31, 2016. Main Outcomes and Measures: The clinical, biological, and
      molecular spectrum of AOA1 and genotype-phenotype correlations. Results: The
      diagnosis of AOA1 was confirmed in 80 patients (46 men [58%] and 34 women [42%];
      mean [SD] age at onset, 7.7 [7.4] years) from 51 families, including 57 new (with
      8 new mutations) and 23 previously described patients. Elevated levels of alpha
      fetoprotein (AFP) were found in 33 patients (41%); hypoalbuminemia, in 50 (63%).
      Median AFP level was higher in patients with AOA1 (6.0 ng/mL; range, 1.1-17.0
      ng/mL) than in patients without ataxia (3.4 ng/mL; range, 0.8-17.2 ng/mL; P <
      .01). Decreased albumin levels (rho = -0.532) and elevated AFP levels (rho =
      0.637) were correlated with disease duration. The p.Trp279* mutation, initially
      reported as restricted to the Portuguese founder haplotype, was discovered in 53
      patients with AOA1 (66%) with broad white racial origins. Oculomotor apraxia was
      found in 49 patients (61%); polyneuropathy, in 74 (93%); and cerebellar atrophy,
      in 78 (98%). Oculomotor apraxia correlated with the severity of ataxia and
      mutation type, being more frequent with deletion or truncating mutations (83%)
      than with presence of at least 1 missense variant (17%; P < .01). Mean (SD) age
      at onset was higher for patients with at least 1 missense mutation (17.7 [11.4]
      vs 5.2 [2.6] years; P < .001). Conclusions and Relevance: The AFP level, slightly
      elevated in a substantial fraction of patients, may constitute a new biomarker
      for AOA1. Oculomotor apraxia may be an optional finding in AOA1 and correlates
      with more severe disease. The p.Trp279* mutation is the most frequent APTX
      mutation in the white population. APTX missense mutations may be associated with
      a milder phenotype.

PMID- 29356832
TI  - Nine-month clinical outcomes in patients with diabetes treated with polymer-free
      sirolimus-eluting stents and 6-month vs. 12-month dual-antiplatelet therapy
      (DAPT).
AB  - BACKGROUND: Diabetes mellitus is known to be associated with worse clinical
      outcomes in patients with coronary artery disease (CAD) undergoing percutaneous
      coronary interventions (PCI) with drug-eluting stents (DES). Defining the optimal
      duration of dual antiplatelet therapy (DAPT) after DES implantation is still
      under debate. The objective of this subgroup analysis of the all-comers ISAR 2000
      registry was to assess the safety and efficacy of a short DAPT (<6 month) versus
      a longer DAPT (>6 month) in patients with diabetes electively treated with the
      polymer-free sirolimus-coated ultrathin strut drug-eluting stent (PF-SES).
      METHODS: Patients who received the PF-SES were investigated in a multicenter all
      comers observational study. The primary endpoint was the 9-month target lesion
      revascularization (TLR) rate, whereas secondary endpoints included the 9-month
      major adverse cardiac event (MACE) and procedural success rates. RESULTS: In all,
      167 patients were treated with DAPT for <=6 months (S-DAPT group) and 350
      patients underwent DAPT treatment for 12 months (L-DAPT group). There was no
      significant difference in the overall MACE rate (4.6% vs. 3.1%, p = 0.441), the 9
      month accumulated stent thrombosis rates (0.8% vs. 0.3%, p = 0.51), or the
      accumulated rate of bleeding complications (5.3% vs. 3.4%, p = 0.341).
      CONCLUSION: PF-SES are safe and effective in daily clinical routine with low
      rates of TLR and MACE in patients with diabetes and stable disease. Our data
      suggest that extending the duration of DAPT beyond 6 months does not improve MACE
      or TLR at 9 months in patients with stable CAD (ClinicalTrials.gov Identifier
      NCT02629575).

PMID- 29356834
TI  - ?

PMID- 29356833
TI  - [Severe lymphopenia in a patient with Crohn's disease].
AB  - We report on a 25-year-old female patient with Crohn's disease and profound
      lymphocytopenia while receiving corticosteroids and azathioprine. Discontinuation
      of azathioprine only resulted in a mild increase in CD4+ T cell numbers; however,
      therapy with the TNFalpha inhibitor adalimumab was initiated for a clinical flare
      and resulted in long-lasting clinical remission and rapid normalization of the
      lymphocytopenia including the respective lymphocyte subsets. Lymphocytopenia is
      frequently observed as a side effect of immunosuppressive therapy. This case
      illustrates that lymphocytopenia may also occur in relation to Crohn's disease
      activity as an extraintestinal manifestation and may then be efficiently treated
      by escalation of immunosuppressive therapy.

PMID- 29356835
TI  - Diabetes in pregnancy: a new decade of challenges ahead.
AB  - Every 10 years, the Diabetic Pregnancy Study Group, a study group of the EASD,
      conducts an audit meeting to review the achievements of the preceding decade and
      to set the directions for research and clinical practice improvements for the
      next decade. The most recent meeting focused on the following areas: improving
      pregnancy outcomes for women with pregestational type 1 diabetes and type 2
      diabetes; the influence of obesity and gestational diabetes on pregnancy
      outcomes; the determinants and assessment of fetal growth and development; and
      public health issues, including consideration of transgenerational consequences
      and economic burden. The audit meeting also considered the likely impact of
      'omics' on research within the field and the potential of these technologies to
      enable precision-medicine approaches to management. Through sharing of the
      findings and ideas of audit meeting participants, the DPSG hopes to promote
      networking, research and advances in clinical care, to improve outcomes for all
      women and their offspring affected by diabetes and obesity in pregnancy.

PMID- 29356836
TI  - Chronic Toxicity of Ferric Iron for North American Aquatic Organisms: Derivation
      of a Chronic Water Quality Criterion Using Single Species and Mesocosm Data.
AB  - Iron is a common pollutant in waters near coal and hard rock mine disturbances.
      The current 1000 ug/L total recoverable chronic criterion for iron (Fe) for
      protection of aquatic life in the United States was developed using very limited
      data in 1976 and has not been revised since. To develop a more scientifically
      based criterion, several chronic laboratory toxicity experiments (> 30 days) were
      conducted with ferric Fe at circumneutral pH on a taxonomically diverse group of
      organisms including brown trout (Salmo trutta), mountain whitefish (Prosopium
      williamsoni), boreal toad tadpoles (Bufo boreas), the oligochaete worm
      Lumbriculus variegatus, the mayfly Hexagenia limbata, and the planarian Dugesia
      dorotocephala. Results of these tests and those of previously published toxicity
      data were used to derive a Final Chronic Value (FCV) of 499 ug/L by using the US
      Environmental Protection Agency's recommended methods based on single species
      toxicity tests. In addition to single species toxicity tests, ferric Fe toxicity
      experiments (10 days) were performed on mesocosms containing naturally colonized
      communities of benthic macroinvertebrates. Fourteen genera in the mesocosms
      occurred at sufficient densities to estimate an iron concentration resulting in
      20% reduction in abundance (EC20). Three of these taxa had EC20s less than the
      FCV of 499 ug/L derived from single species tests: the mayfly Epeorus sp. (335
      ug/L), the caddisfly Micrasema sp. (356 ug/L), and midge Tanytarsini (234 ug/L).
      When mesocosm results were included, the FCV was lowered to 251 ug/L. These
      findings support the suggestion that modernization of water quality criteria
      should include data generated from mesocosm experiments and other lines of
      evidence.

PMID- 29356837
TI  - Limoniibacter endophyticus gen. nov., sp. nov., an alphaproteobacterium isolated
      from the roots of Limonium otolepis.
AB  - A Gram-negative bacterium, designated as strain YIM 690229T, was isolated from
      the roots of Limonium otolepis. The strain was able to grow at 10-40  degrees C
      (optimum, 28-37  degrees C), pH 6.0-8.0 (optimum, 7.0) and in the presence of up
      to 7% NaCl (w/v) (optimum, up to 2.5%). Comparative 16S rRNA gene sequence
      analysis revealed that strain YIM 690229T shared less than 93.9% sequence
      similarities with members within the order Rhizobiales, and was remotely related
      to members of the family Hyphomicrobiaceae. Strain YIM 690229T was characterized
      by the presence of Q-10 as the predominant respiratory lipoquinone. The major
      fatty acids (> 10%) detected were C18:1 omega7c, C16:0, anteiso-C15:0 and summed
      feature 4 (iso-C17:1 I and/or anteiso-C17:1 B). The polar lipids consisted of
      diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylmethylethanoamine and two unidentified lipids.
      The genomic DNA G + C content was 57.2 mol%. Data from this polyphasic taxonomy
      study suggested that strain YIM 690229T should be classified as a new species of
      a new genus within the family Hyphomicrobiaceae for which the name Limoniibacter
      endophyticus gen. nov., sp. nov., is proposed. The type species of the genus
      Limoniibacter gen. nov. is Limoniibacter endophyticus. The type strain of the
      species Limoniibacter endophyticus sp. nov. is YIM 690229T (= KCTC 42097T = JCM
      30141T = CCTCC AB 2014130T = CGMCC 1.12906T).

PMID- 29356839
TI  - ?

PMID- 29356838
TI  - ["Antibiotic stewardship throughout the country"].

PMID- 29356840
TI  - ?

PMID- 29356842
TI  - Test yourself: weakness and wasting of forearm.

PMID- 29356841
TI  - Catechin supplementation prevents kidney damage in rats repeatedly exposed to
      cadmium through mitochondrial protection.
AB  - Nephrotoxicity is recognized as a serious disorder affected by chronic cadmium
      exposure. Imbalance between radical generation and elimination is considered a
      critical factor involved in the initiation and progression of renal injury caused
      by this heavy metal. The present study investigated the possible protection by
      catechin, a natural phenolic antioxidant, against cadmium nephrotoxicity and
      elucidated its potential mechanism. Male Wistar rats were assigned to receive
      vehicle, cadmium (CdCl2 2 mg/kg, i.p.) and cadmium plus catechin (25, 50, and 100
      mg/kg, orally, respectively). After 4 weeks of treatment, rats exposed to cadmium
      demonstrated a marked rise in blood urea nitrogen and creatinine, a fall in
      creatinine clearance, and renal pathologies like severe tubular damage,
      apoptosis, and abnormal mitochondrial structure. Significant increases in
      malondialdehyde, nitric oxide, and tumor necrosis factor-alpha, while reductions
      in antioxidant thiols, superoxide dismutase, and catalase, were also detected in
      the kidney tissues of cadmium-intoxicated rats. These alterations were associated
      with mitochondrial dysfunction as supported by an increase in mitochondrial
      reactive oxygen species production and a decline in mitochondrial membrane
      potential. Treatment with catechin significantly attenuated all the changes
      caused by cadmium. These findings suggest that catechin effectively protects the
      kidney against toxic effect of cadmium, presumably through its antioxidant, anti
      inflammation, and mitochondrial protection. The study outcomes not only add
      evidence to reinforce the medical benefits of catechin but also, most
      importantly, give rise to a prospect of developing renal preventive strategy for
      individuals who are at risk of cadmium contamination by means of catechin
      supplementation.

PMID- 29356843
TI  - Hairline fractures following volar plating of the distal radius: a recently
      recognized hardware-related complication.
AB  - OBJECTIVES: Intraoperative hairline longitudinal fractures were recently reported
      in association with distal radius volar plating. Our aim was to further analyze
      this newly described complication. METHODS: A retrospective radiographic and
      chart review was performed on 225 patients who underwent distal radius plating
      between June 2013 and June 2015. The Acu-Loc/Acu-Loc2(c) plating system (Acumed,
      Hillsboro, OR, USA) was used in 208 cases, and the VariAx(c) plating system
      (Stryker, Kalamazoo, MI, USA) was used in 17 cases. Three independent reviewers
      performed a blind evaluation of all relevant radiographs for the occurrence of
      longitudinal fractures around the plate, and validity was considered only when
      there was agreement among all three of them. RESULTS: Hairline longitudinal
      fractures were identified in 57 cases (25%), 55 with the Acu-Loc/Acu-Loc2(c)
      system and 2 with the VariAx(c) system. All fractures occurred with volar
      plating. Fracture occurrence was associated with age over 59 years, female
      gender, extra-articular fractures, and the use of Hexalobe screws (Acu-Loc/Acu
      Loc2(c) system). CONCLUSIONS: We believe that the source of fracture occurrence
      lies within the screw design and that better screw design and possibly tapping in
      patients at risk may reduce the occurrence of intraoperative hairline
      longitudinal fractures. Further clinical and biomechanical research is needed to
      better understand this newly reported complication.

PMID- 29356844
TI  - Characteristics and management of penetrating abdominal injuries in a German
      level I trauma center.
AB  - PURPOSE: Penetrating abdominal injuries caused by stabbing or firearms are rare
      in Germany, thus there is lack of descriptive studies. The management of
      hemodynamically stable patients is still under dispute. The aim of this study is
      to review and improve our management of penetrating abdominal injuries. METHODS:
      We retrospectively reviewed a 10-year period from the Trauma Registry of our
      level I trauma center. The data of all patients regarding demographics, clinical
      and outcome parameters were examined. Further, charts were reviewed for FAST and
      CT results and correlated with intraoperative findings. RESULTS: A total of 115
      patients with penetrating abdominal trauma (87.8% men) were analyzed. In 69
      patients, the injuries were caused by interpersonal violence and included 88 stab
      and 4 firearm wounds. 8 patients (6.9%) were in a state of shock at presentation.
      52 patients (44.8%) suffered additional extraabdominal injuries. 38 patients were
      managed non-operatively, while almost two-thirds of all patients underwent
      surgical treatment. Hereof, 20 laparoscopies and 3 laparotomies were
      nontherapeutic. There were two missed injuries, but no patient experienced
      morbidity or mortality related to delay in treatment. 106 (92.2%) FAST and 91
      (79.3%) CT scans were performed. Sensitivity and specificity of FAST were 59.4
      and 94.2%, while those of CT were 93.2 and 85.1%, respectively. CONCLUSION: In
      hemodynamically stable patients presenting with penetrating abdominal trauma, CT
      is indicated and the majority of injuries can be managed conservatively. If
      surgical treatment is required, diagnostic laparoscopy for stable patients is
      feasible to avoid nontherapeutic laparotomy.

PMID- 29356845
TI  - Risk of Subsequent Fragility Fractures Observed After Low-Trauma Ankle Fractures.
AB  - While fragility fractures (FFs) are one of the strongest predictors of subsequent
      osteoporotic fractures, it remains unclear whether low-trauma ankle fractures
      have this ability. The aim of the study was to identify the characteristics of
      patients with low-trauma ankle FFs who develop subsequent FFs. The OPTIMUS
      initiative is a strategy to improve osteoporosis treatment post-FF in orthopedic
      clinics. FRAX scores without BMD (FRAX-BMI) were calculated at time of inclusion.
      Recurrent FFs were recorded over a 48-month follow-up. All FFs were X-ray
      confirmed. A total of 265 patients with initial ankle FF were included (190
      women; mean age 62.8 +/- 9.6 years), of whom 15 developed new FFs. Patients with
      ankle FFs had longer time until recurrence and lower 2-year incidence of
      recurrent FFs (3.2%) compared with those having wrist FFs (9.0%) or other initial
      FFs (9.6%), and 4-year incidence rates of 6.2, 13.4, and 15.3%, respectively (log
      rank test, p = 0.001). With an ankle FF at inclusion, recurrent FFs were more
      frequent in patients with previous FF (6.2 per 100 patient-years; p < 0.01) or
      high-risk FRAX-BMI scores pre- or post-FF (2.4 or 2.0 per 100 patient-years,
      respectively; ns), compared to patients without any of these conditions (0.7 per
      100 patient-years). Ankle FFs represent a clinical opportunity for identifying at
      risk patients who should be targeted for treatment (previous FFs and/or high-risk
      FRAX). Because of mechanical factors and other contributors involved, ankle FFs
      themselves do not predict subsequent FFs overall, and their inclusion in FRAX-BMI
      risk calculation may thus not be warranted.

PMID- 29356846
TI  - Epigenetics and Epigenomics of Plants.
AB  - The genetic material DNA in association with histone proteins forms the complex
      structure called chromatin, which is prone to undergo modification through
      certain epigenetic mechanisms including cytosine DNA methylation, histone
      modifications, and small RNA-mediated methylation. Alterations in chromatin
      structure lead to inaccessibility of genomic DNA to various regulatory proteins
      such as transcription factors, which eventually modulates gene expression.
      Advancements in high-throughput sequencing technologies have provided the
      opportunity to study the epigenetic mechanisms at genome-wide levels. Epigenomic
      studies using high-throughput technologies will widen the understanding of
      mechanisms as well as functions of regulatory pathways in plant genomes, which
      will further help in manipulating these pathways using genetic and biochemical
      approaches. This technology could be a potential research tool for displaying the
      systematic associations of genetic and epigenetic variations, especially in terms
      of cytosine methylation onto the genomic region in a specific cell or tissue. A
      comprehensive study of plant populations to correlate genotype to epigenotype and
      to phenotype, and also the study of methyl quantitative trait loci (QTL) or
      epiGWAS, is possible by using high-throughput sequencing methods, which will
      further accelerate molecular breeding programs for crop improvement. Graphical
      Abstract.

PMID- 29356847
TI  - Revolution in Genotyping Platforms for Crop Improvement.
AB  - In the past decade, the application of high-throughput sequencing to crop
      genotyping has given rise to novel platforms capable of genotyping tens of
      thousands of genome-wide DNA markers. Coupled with the decreasing costs of
      sequencing, this rapid increase in markers allows accelerated and highly accurate
      genotyping of entire crop populations and diversity sets using single nucleotide
      polymorphisms (SNPs). These revolutionary advances accelerate crop improvement by
      facilitating a more precise connection of phenotype to genotype through
      association studies, linkage mapping and diversity analysis. The platforms
      driving the advances in genotyping are array technologies and genotyping by
      sequencing (GBS) methods, which include both low-coverage whole genome
      resequencing (skim sequencing) and reduced representation sequencing (RRS)
      approaches. Here, we outline and compare these genotyping platforms and provide a
      perspective on the promising future of crop genotyping. While SNP arrays provide
      high quality, simple handling, and unchallenging analysis, the lower cost of RRS
      and the greater data volume produced by skim sequencing suggest that use of GBS
      will become more prevalent in crop genomics as sequencing costs decrease and data
      analysis becomes more streamlined. Graphical Abstract.

PMID- 29356848
TI  - Artificial Gene Amplification in Escherichia coli Reveals Numerous Determinants
      for Resistance to Metal Toxicity.
AB  - When organisms are subjected to environmental challenges, including growth
      inhibitors and toxins, evolution often selects for the duplication of endogenous
      genes, whose overexpression can provide a selective advantage. Such events occur
      both in natural environments and in clinical settings. Microbial cells-with their
      large populations and short generation times-frequently evolve resistance to a
      range of antimicrobials. While microbial resistance to antibiotic drugs is well
      documented, less attention has been given to the genetic elements responsible for
      resistance to metal toxicity. To assess which overexpressed genes can endow gram
      negative bacteria with resistance to metal toxicity, we transformed a collection
      of plasmids overexpressing all E. coli open reading frames (ORFs) into naive
      cells, and selected for survival in toxic concentrations of six transition
      metals: Cd, Co, Cu, Ni, Ag, Zn. These selections identified 48 hits. In each of
      these hits, the overexpression of an endogenous E. coli gene provided a selective
      advantage in the presence of at least one of the toxic metals. Surprisingly, the
      majority of these cases (28/48) were not previously known to function in metal
      resistance or homeostasis. These findings highlight the diverse mechanisms that
      biological systems can deploy to adapt to environments containing toxic
      concentrations of metals.

PMID- 29356849
TI  - En route to the liver: an fishbone's unexpected journey.

PMID- 29356850
TI  - Are septic children really just "septic little adults"?

PMID- 29356851
TI  - Fast confirmation of correct position of distal perfusion cannula during
      venoarterial extracorporeal membrane oxygenation.

PMID- 29356852
TI  - Reduction of cardiac herniation following intrapericardial pneumonectomy with
      pleural perfusion of saline.

PMID- 29356853
TI  - Should this elderly patient be admitted to the ICU?

PMID- 29356854
TI  - Limited value of end-expiratory inferior vena cava diameter to predict fluid
      responsiveness impact of intra-abdominal pressure.
AB  - PURPOSE: We sought to determine the diagnostic ability of the end-expiratory
      inferior vena cava diameter (IVCEE) to predict fluid responsiveness (FR) and the
      potential confounding effect of intra-abdominal pressure (IAP). METHODS: In this
      multicenter study, 540 consecutive ventilated patients with shock of various
      origins underwent an echocardiographic assessment by experts. The IVCEE, velocity
      time integral (VTI) of the left ventricular outflow tract (LVOT) and intra
      abdominal pressure (IAP) were measured. Passive leg raising (PLR) was then
      systematically used to perform a reversible central blood volume expansion. FR
      was defined by an increase in LVOT VTI >= 10% after 1 min of PLR. RESULTS: Since
      IVCEE was not obtained in 117 patients (22%), 423 were studied (septic shock:
      56%), 129 of them (30%) having elevated IAP (>= 12 mmHg) and 172 of them (41%)
      exhibiting FR. IVCEE <= 13 mm predicted FR with a specificity of at least 80% in
      62 patients (15%), while IVCEE >= 25 mm predicted the absence of FR with a
      specificity of at least 80% in 61 patients (14%). In the remaining 300 patients
      (71%), the intermediate value of IVCEE did not allow predicting FR. An adjusted
      relationship between IVCEE and FR was observed while this relationship was less
      pronounced in patients with IAP >= 12 mmHg. CONCLUSIONS: Measurement of IVCEE in
      ventilated patients is moderately feasible and poorly predicts FR, with IAP
      acting as a confounding factor. IVCEE might add some value to guide fluid therapy
      but should not be used alone for fluid prediction purposes.

PMID- 29356855
TI  - Combining monoenergetic extrapolations from dual-energy CT with iterative
      reconstructions: reduction of coil and clip artifacts from intracranial aneurysm
      therapy.
AB  - PURPOSE: To compare and to combine iterative metal artifact reduction (MAR) and
      virtual monoenergetic extrapolations (VMEs) from dual-energy computed tomography
      (DECT) for reducing metal artifacts from intracranial clips and coils. METHODS:
      Fourteen clips and six coils were scanned in a phantom model with DECT at 100 and
      150SnkVp. Four datasets were reconstructed: non-corrected images (filtered-back
      projection), iterative MAR, VME from DECT at 120 keV, and combined iterative MAR
      + VME images. Artifact severity scores and visibility of simulated, contrast
      filled, adjacent vessels were assessed qualitatively and quantitatively by two
      independent, blinded readers. RESULTS: Iterative MAR, VME, and combined iterative
      MAR + VME resulted in a significant reduction of qualitative (p < 0.001) and
      quantitative clip artifacts (p < 0.005) and improved the visibility of adjacent
      vessels (p < 0.05) compared to non-corrected images, with lowest artifact scores
      found in combined iterative MAR + VME images. Titanium clips demonstrated less
      artifacts than Phynox clips (p < 0.05), and artifact scores increased with clip
      size. Coil artifacts increased with coil size but were reducible when applying
      iterative MAR + VME compared to non-corrected images. However, no technique
      improved the severe artifacts from large, densely packed coils. CONCLUSIONS:
      Combining iterative MAR with VME allows for an improved metal artifact reduction
      from clips and smaller, loosely packed coils. Limited value was found for large
      and densely packed coils.

PMID- 29356856
TI  - Ruptured middle cerebral artery aneurysms with a concomitant intraparenchymal
      hematoma: the role of hematoma volume.
AB  - PURPOSE: To study whether clinical outcome data from our patient cohort could
      give support to the new recommendation in the AHA/ASA guidelines for the
      management of aneurysmal subarachnoid hemorrhage that states "that microsurgical
      clipping may receive increased consideration in patients with ruptured middle
      cerebral artery (MCA) aneurysms and large (>50 mL) intraparenchymal hematomas",
      while clinical outcome data supporting this recommendation are sparse. METHODS:
      We reviewed the clinical and radiological data of 81 consecutive patients with
      MCA aneurysms and concomitant hematomas admitted between January 2006 and
      December 2015. The relation between (semi-automatically quantified) hematoma
      volume (< or > 50 ml), neurological condition on admission (poor: GCS < 8 or non
      reactive pupils), treatment strategies (no treatment, coiling, or clipping with
      or without decompression and/or clot removal), and outcome (favorable: mRS score
      0-3) was evaluated. RESULTS: Clinical outcome data were available for 76
      patients. A significant difference in favorable outcome (17 vs 68%) was seen when
      comparing patients with poor and good neurological condition on admission (p <
      0.01). Patients with hematomas > 50 ml had similar outcomes for coiling and
      clipping, all underwent decompression. Patients with hematomas < 50 ml did not
      show differences in favorable outcome when comparing coiling and clipping with
      (33 and 31%) or without decompression (90 and 88%). CONCLUSION: Poor neurological
      condition on admission, and not large intraparenchymal hematoma volume, was
      associated with poor clinical outcome. Therefore, even in patients with large
      hematomas, the neurological condition on admission and the aneurysm configuration
      seem to be equally important factors to determine the most appropriate treatment
      strategy.

PMID- 29356858
TI  - [Rare cause of a supraclavicular swelling].

PMID- 29356857
TI  - Fate of the three embryonic dural sinuses in infants: the primitive tentorial
      sinus, occipital sinus, and falcine sinus.
AB  - PURPOSE: The primitive tentorial, occipital, and falcine sinuses are thought to
      attain the adult pattern or regress between the fetal stage and adulthood. The
      anatomy of these three primitive dural sinuses has seldom been studied in the
      infant population, and it remains unclear when these dural sinuses reach the
      adult condition. Using computed tomography digital subtraction venography (CT
      DSV), we analyzed the anatomy of these embryonic dural sinuses in infants.
      METHODS: We included 13 infants who underwent CT-DSV prior to neurosurgery and 35
      cases with unruptured cerebral aneurysms as normal adult controls. Three
      embryonic dural sinuses, i.e., the primitive tentorial, occipital, and falcine
      sinuses, were retrospectively analyzed in CT-DSV images of infants and adults. We
      also analyzed the drainage patterns of the superficial middle cerebral vein
      (SMCV), determined by the connection between the primitive tentorial sinus and
      the cavernous sinus. RESULTS: The primitive tentorial, occipital, and falcine
      sinuses were present in 15.4%, 46.2%, and none of the infants, respectively, and
      in 10.0, 8.6, and 2.9% of the adults, respectively. The difference in SMCV
      draining pattern between infants and adults was insignificant. The incidence of
      the occipital sinus was significantly higher in infants than in adults.
      CONCLUSIONS: The connection between the primitive tentorial sinus and the
      cavernous sinus appears to be established before birth. The occipital sinus is
      formed at the embryonic stage and mostly regresses after infancy. The falcine
      sinus is usually obliterated prenatally. Our findings form the basis for
      interventions by pediatric interventional neuroradiologists and neurosurgeons.

PMID- 29356859
TI  - Correction to: Association between vaginal bulge and anatomical pelvic organ
      prolapse during pregnancy and postpartum: an observational study.
AB  - The last paragraph of the "Interpretation" section contains an error.

PMID- 29356860
TI  - Anti-estrogenic activity of tris(2,3-dibromopropyl) isocyanurate through
      disruption of co-activator recruitment: experimental and computational studies.
AB  - As a potential endocrine disruptor, tris(2,3-dibromopropyl) isocyanurate (TBC)
      has previously been demonstrated to reduce expression of estrogen-dependent
      vitellogenin (vtg) mRNA in adult zebrafish. However, the underlying toxicity
      pathways and molecular mechanisms involved in TBC-induced endocrine disruption
      remain elusive. In the current study, E-Screen and MVLN assays were employed to
      explore the potential anti-estrogenic effects of TBC via the estrogen receptor
      alpha (ERalpha)-mediated signaling pathway. Within a dose range between 1 * 10- 9
      and 1 * 10- 7 M, TBC significantly inhibited 17beta-estradiol (E2)-induced cell
      proliferation in a breast cancer cell line. The luciferase activity induced by E2
      was also significantly inhibited by TBC in a dose-dependent manner. Moreover,
      neither TBC nor E2 affected proliferation of the ERalpha-negative breast cancer
      cell line MDA-MB-231. These experimental results confirmed that TBC has anti
      estrogenic effects by affecting the ERalpha-mediated signaling pathway. By
      comparing TBC with known antagonists of ERalpha, we found that TBC has similar
      molecular structure as certain co-activator binding inhibitors. Therefore, using
      molecular docking and molecular dynamics simulations, TBC was further predicted
      to competitively occupy the surface site of ERalpha rather than the canonical E2
      binding pocket of ERalpha, thus disrupt subsequent co-activator recruitment and
      transcription activation. Our findings elucidate the anti-estrogenic mechanism of
      TBC at the atomic level and highlight the biological importance of surface sites
      of nuclear receptors for a risk assessment of potential environmental pollutants.

PMID- 29356861
TI  - Identification of approved drugs as potent inhibitors of pregnane X receptor
      activation with differential receptor interaction profiles.
AB  - Activation of pregnane X receptor (PXR) results in the induction of first-pass
      metabolism and drug efflux. Hereby, PXR may cause adverse drug reactions or
      therapeutic failure of drugs. PXR inhibition is thus an attractive option to
      minimise adverse effects or to improve therapeutic efficiencies; however, only a
      limited number of antagonists have been identified so far. We performed a cell
      based high-throughput screen to identify PXR antagonists, using a library of
      approved and investigational drugs. Two approved drugs, pimecrolimus and
      pazopanib, emerged as novel potent antagonists of PXR activation, with IC50
      values of 1.2 and 4.1 uM, respectively. We further characterised these with
      respect to receptor specificity, assembly of the PXR ligand-binding domain (LBD)
      and interactions with co-factors. In vitro and in silico assays were carried out
      to identify the site(s) of interaction with the PXR LBD. Primary human
      hepatocytes were used to investigate antagonism of the induction of endogenous
      PXR target genes. Pimecrolimus and pazopanib did not affect the transcriptional
      activity of other nuclear receptors. Both induced the release of co-repressor
      from PXR and likewise interfered with agonist-induced recruitment of co
      activator. Cumulative evidence from cellular and in vitro assays, as well as
      molecular docking, suggested additional or exclusive binding outside the PXR
      ligand-binding pocket for both. The compounds differentially antagonised the
      induction of PXR-regulated genes by rifampicin in primary human hepatocytes. In
      conclusion, we here have identified two approved drugs as novel potent PXR
      inhibitors with differential receptor interaction profiles and gene selectivity
      in primary human hepatocytes.

PMID- 29356862
TI  - Flame retardants, hexabromocyclododecane (HCBD) and tetrabromobisphenol a
      (TBBPA), alter secretion of tumor necrosis factor alpha (TNFalpha) from human
      immune cells.
AB  - Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are flame
      retardants, used in a variety of applications, which contaminate the environment
      and are found in human blood. HBCD and TBBPA have been shown to alter the tumor
      killing function of natural killer (NK) lymphocytes and the secretion of the
      inflammatory cytokines interferon gamma (IFNgamma) and interleukin 1 beta (IL
      1beta). The current study examined the effects of HBCD and TBBPA on secretion of
      the critical pro-inflammatory cytokine tumor necrosis factor alpha (TNFalpha)
      from human immune cells. Preparations of human immune cells that ranged in
      complexity were studied to determine if the effects of the compounds were
      consistent as the composition of the cell preparation became more heterogeneous.
      Cell preparations studied were: NK cells, monocyte-depleted (MD) peripheral blood
      mononuclear cells (PBMCs), and PBMCs. Exposure of NK cells to higher
      concentrations of HBCD (5 and 2.5 uM) caused decreased secretion of TNFalpha.
      However, when the cell preparation contained T lymphocytes (MD-PBMCs and PBMCs)
      these same concentrations of HBCD increased TNFalpha secretion as did nearly all
      other concentrations. This suggests that HBCD's ability to increase TNFalpha
      secretion from immune cells was dependent on the presence of T lymphocytes. In
      contrast, exposures to TBBPA decreased the secretion of TNFalpha from all immune
      cell preparations regardless of the composition of the cell preparation. Further,
      HBCD-induced increases in TNFalpha secretion utilized the p38 MARK pathway. Thus,
      both HBCD and TBBPA may have the capacity to disrupt the inflammatory response
      with HBCD having the potential to cause chronic inflammation.

PMID- 29356863
TI  - Somatosensory modulation of perceptual vestibular detection.
AB  - Vestibular-multisensory interactions are essential for self-motion, navigation
      and postural stability. Despite evidence suggesting shared brain areas between
      vestibular and somatosensory inputs, no study has yet investigated whether
      somatosensory information influences vestibular perception. Here, we used signal
      detection methods to identify whether somatosensory stimulation might interact
      with vestibular events in a vestibular detection task. Participants were
      instructed to detect near-threshold vestibular roll-rotation sensations delivered
      by galvanic vestibular stimulation in one-half of experimental trials. A
      vibrotactile signal occurred to the index fingers of both hands in half of the
      trials, independent of vestibular signals. We found that vibrotactile
      somatosensory stimulation decreased perceptual vestibular sensitivity. The
      results are compatible with a gain regulation mechanism between vestibular and
      somatosensory modalities.

PMID- 29356864
TI  - Ceci n'est pas un walrus: lexical processing in vigilance performance.
AB  - Vigilance, or the ability to sustain attention for extended periods of time, has
      traditionally been examined using a myriad of symbolic, cognitive, and sensory
      tasks. However, the current literature indicates a relative lack of empirical
      investigation on vigilance performance involving lexical processing. To address
      this gap in the literature, the present study examined the effect of stimulus
      meaning on vigilance performance (i.e., lure effects). A sample of 126 observers
      completed a 12-min lexical vigilance task in a research laboratory. Observers
      were randomly assigned to a standard task (targets and neutral events only) or a
      lure task (lures, targets, and neutral events presented), wherein lures were
      stimuli that were categorically similar to target stimuli. A novel analytical
      approach was utilized to examine the results; the lure groups were divided based
      on false alarm performance post hoc. Groups were further divided to demonstrate
      that the presence of lure stimuli significantly affects the decision-making
      criteria used to assess the performance of lexical vigilance tasks. We also
      discuss the effect of lure stimuli on measures related to signal detection theory
      (e.g., sensitivity and response bias).

PMID- 29356865
TI  - Testing the perceptual equivalence hypothesis in mental rotation of 3D stimuli
      with visual and tactile input.
AB  - Previous studies on mental rotation (i.e., the ability to imagine objects
      undergoing rotation; MR) have mainly focused on visual input, with comparatively
      less information about tactile input. In this study, we examined whether the
      processes subtending MR of 3D stimuli with both input modalities are perceptually
      equivalent (i.e., when learning within-modalities is equal to transfers-of
      learning between modalities). We compared participants' performances in two
      consecutive task sessions either in no-switch conditions (Visual->Visual or
      Tactile->Tactile) or in switch conditions (Visual->Tactile or Tactile->Visual).
      Across both task sessions, we observed MR response differences with visual and
      tactile inputs, as well as difficult transfer-of-learning. In no-switch
      conditions, participants showed significant improvements on all dependent
      measures. In switch conditions, however, we only observed significant
      improvements in response speeds with tactile input (RTs, intercepts, slopes:
      Visual->Tactile) and close to significant improvement in response accuracy with
      visual input (Tactile->Visual). Model fit analyses (of the rotation angle effect
      on RTs) also suggested different specification in learning with tactile and
      visual input. In "Session 1", the RTs fitted similarly well to the rotation
      angles, for both types of perceptual responses. However, in "Session 2", trend
      lines in the fitting analyses changed in a stark way, in the switch and tactile
      no-switch conditions. These results suggest that MR with 3D objects is not
      necessarily a perceptually equivalent process. Specialization (and priming) in
      the exploration strategies (i.e., speed-accuracy trade-offs) might, however, be
      the main factor at play in these results-and not MR differences in and of
      themselves.

PMID- 29356866
TI  - Retrofitting baculoviral vector with Sleeping Beauty transposon system: competent
      for long-term reporter gene imaging in vivo.
AB  - Reporter gene imaging is widely used for non-invasively detecting tumorigenesis,
      trafficking therapeutic cells, and monitoring treatment effect. Baculoviral
      vectors (BVs) have been utilized as transgenic vectors in the reporter gene
      imaging systems in recent years. However, BV-mediated report gene imaging can
      only provide short-term investigation due to its transient transgene expression,
      which is incompetent for the long-term applications. In the current study, we
      reconstructed a series of hybrid BVs with several elements, to investigate the
      feasibility of this hybrid BV-mediated long-term reporter gene imaging in vivo.
      We showed that with the indispensable assistance of a positive-selection process,
      hybrid BV containing Sleeping Beauty 100* (SB) transposon system (BV-SB) could
      significantly prolong the enhanced green fluorescent protein (eGFP) expression
      for at least 180 days in vitro at nearly 100% eGFP positive percentage and over
      1011 arbitrary unit total fluorescence intensity, whereas other hybrid BV
      mediated transgene expression gradually faded in only 20 days. Furthermore, BV-SB
      mediated eGFP fluorescent reporter gene imaging monitored tumorigenesis in the
      nude mice for at least 35 days. In addition, we exploited the glucagon-like
      peptide 1 receptor (glp-1r) gene as a radionuclide reporter gene for in vivo
      micro-PET imaging. At 50th day post-tumor transplantation, the micro-PET imaging
      showed considerable radiotracer-receptor-binding in vivo, resulted by stable high
      level of BV-SB-mediated GLP-1R expression in tumor. In summary, we retrofitted BV
      with the SB transposon system to make it competent for the long-term reporter
      gene imaging in vivo, which might broaden the application scopes of BV in the
      long-term molecular imaging and other biomedicine research fields.

PMID- 29356867
TI  - Effect of different CO2 concentrations on biomass, pigment content, and lipid
      production of the marine diatom Thalassiosira pseudonana.
AB  - The marine diatom Thalassiosira pseudonana grown under air (0.04% CO2) and 1 and
      5% CO2 concentrations was evaluated to determine its potential for CO2 mitigation
      coupled with biodiesel production. Results indicated that the diatom cultures
      grown at 1 and 5% CO2 showed higher growth rates (1.14 and 1.29 div day-1,
      respectively) and biomass productivities (44 and 48 mgAFDWL-1 day-1) than air
      grown cultures (with 1.13 div day-1 and 26 mgAFDWL-1 day-1). The increase of CO2
      resulted in higher cell volume and pigment content per cell of T. pseudonana.
      Interestingly, lipid content doubled when air was enriched with 1-5% CO2.
      Moreover, the analysis of the fatty acid composition of T. pseudonana revealed
      the predominance of monounsaturated acids (palmitoleic-16:1 and oleic-18:1) and a
      decrease of the saturated myristic acid-14:0 and polyunsaturated fatty acids
      under high CO2 levels. These results suggested that T. pseudonana seems to be an
      ideal candidate for biodiesel production using flue gases.

PMID- 29356868
TI  - Enhancement of Schizochytrium DHA synthesis by plasma mutagenesis aided with
      malonic acid and zeocin screening.
AB  - Schizochytrium sp. accumulates valuable polyunsaturated fatty acid (PUFA), such
      as docosahexaenoic acid (DHA). In order to increase DHA synthesis in this
      microorganism, physical or chemical mutagenesis aided with powerful screening
      methods are still preferable, as its DHA synthetic pathway has not yet been
      clearly defined for gene manipulation. To breed this agglomerate microorganism of
      thick cell wall and rather large genome for increasing lipid content and DHA
      percentage, a novel strategy of atmospheric and room temperature plasma (ARTP)
      mutagenesis coupled with stepped malonic acid (MA) and zeocin resistance
      screening was developed. The final resulted mutant strain mz-17 was selected with
      1.8-fold increased DHA production. Accompanied with supplementation of Fe2+ in
      shake flask cultivation, DHA production of 14.0 g/L on average was achieved. This
      work suggests that ARTP mutation combined with stepped MA and zeocin resistance
      screening is an efficient method of breeding Schizochytrium sp. of high DHA
      production, and might be applied on other microorganisms for obtaining higher
      desired PUFA products.

PMID- 29356869
TI  - Thymoquinone inhibits biofilm formation and has selective antibacterial activity
      due to ROS generation.
AB  - The present study was aimed to investigate the antibacterial potential and
      antibiofilm activity of thymoquinone and its mechanism of action. Antibacterial
      activity of thymoquinone was studied using minimum inhibitory concentration,
      minimum bactericidal concentration, time-kill assay, and post-antibiotic effect.
      Thymoquinone exhibited antibacterial activity against both Gram-negative and Gram
      positive bacteria. In this study, the minimum inhibitory concentration was found
      to be in the range of 1.56 to 100 MUg/ml. Scanning electron microscopy imaging
      revealed changes in cell morphology with dents, cell lysis, and reduction in cell
      size. Live/dead imaging using acridine orange and ethidium bromide confirmed the
      bactericidal activity as treated bacteria showed selective uptake of ethidium
      bromide over acridine orange. Cell viability was also studied using HaCaT (human
      keratinocytes) cell line by MTT assay, and IC90 value was found to be 50 MUg/ml.
      This IC90 value was higher than that of MICbacteria (except for MIC of E. coli),
      demonstrating that its selectivity is higher towards bacteria than normal human
      cells. Thymoquinone also showed promising antibiofilm activity against Gram
      negative (E. coli and P. aeruginosa) and Gram-positive bacteria (B. subtilis and
      S. aureus), which was studied by crystal violet assay, CFU method, and SEM. For
      understanding the mechanism of action of thymoquinone, DiSC3, NPN, and ROS assay
      was performed. DiSC3 and NPN assay has not shown any membrane damage whereas
      bacterial cells treated with thymoquinone at MIC showed increased
      dichlorofluorescin fluorescence, suggesting that the probable mechanism of action
      of thymoquinone against bacterial cells is due to the production of reactive
      oxygen species.

PMID- 29356870
TI  - A multi-phase approach to select new wine yeast strains with enhanced
      fermentative fitness and glutathione production.
AB  - The genetic improvement of winemaking yeasts is a virtually infinite process, as
      the design of new strains must always cope with varied and ever-evolving
      production contexts. Good wine yeasts must feature both good primary traits,
      which are related to the overall fermentative fitness of the strain, and
      secondary traits, which provide accessory features augmenting its technological
      value. In this context, the superiority of "blind," genetic improvement
      techniques, as those based on the direct selection of the desired phenotype
      without prior knowledge of the genotype, was widely proven. Blind techniques such
      as adaptive evolution strategies were implemented for the enhancement of many
      traits of interest in the winemaking field. However, these strategies usually
      focus on single traits: this possibly leads to genetic tradeoff phenomena, where
      the selection of enhanced secondary traits might lead to sub-optimal primary
      fermentation traits. To circumvent this phenomenon, we applied a multi-step and
      strongly directed genetic improvement strategy aimed at combining a strong
      fermentative aptitude (primary trait) with an enhanced production of glutathione
      (secondary trait). We exploited the random genetic recombination associated to a
      library of 69 monosporic clones of strain UMCC 855 (Saccharomyces cerevisiae) to
      search for new candidates possessing both traits. This was achieved by
      consecutively applying three directional selective criteria: molybdate resistance
      (1), fermentative aptitude (2), and glutathione production (3). The strategy
      brought to the selection of strain 21T2-D58, which produces a high concentration
      of glutathione, comparable to that of other glutathione high-producers, still
      with a much greater fermentative aptitude.

PMID- 29356871
TI  - Cold atmospheric pressure plasma causes protein denaturation and endoplasmic
      reticulum stress in Saccharomyces cerevisiae.
AB  - Cold atmospheric pressure plasma (CAP) does not cause thermal damage or generate
      toxic residues; hence, it is projected as an alternative agent for sterilization
      in food and pharmaceutical industries. The fungicidal effects of CAP have not yet
      been investigated as extensively as its bactericidal effects. We herein examined
      the effects of CAP on yeast proteins using a new CAP system with an improved
      processing capacity. We demonstrated that protein ubiquitination and the
      formation of protein aggregates were induced in the cytoplasm of yeast cells by
      the CAP treatment. GFP-tagged Tsa1 and Ssa1, an H2O2-responsive molecular
      chaperone and constitutively expressed Hsp70, respectively, formed cytoplasmic
      foci in CAP-treated cells. Furthermore, Tsa1 was essential for the formation of
      Ssa1-GFP foci. These results indicate that the denaturation of yeast proteins was
      caused by CAP, at least partially, in a H2O2-dependent manner. Furthermore,
      misfolded protein levels in the endoplasmic reticulum (ER) and the
      oligomerization of Ire1, a key sensor of ER stress, were enhanced by the
      treatment with CAP, indicating that CAP causes ER stress in yeast cells as a
      specific phenomenon to eukaryotic cells. The pretreatment of yeast cells at 37 
      degrees C significantly alleviated cell death caused by CAP. Our results strongly
      suggest that the induction of protein denaturation is a primary mechanism of the
      fungicidal effects of CAP.

PMID- 29356873
TI  - Clinical outcomes and costs of reusable and single-use flexible
      ureterorenoscopes: a prospective cohort study.
AB  - The purpose of this study is to analyze clinical outcomes and costs of single-use
      flexible ureterorenoscopes in comparison with reusable flexible ureterorenoscopes
      in a tertiary referral center. Prospectively, 68 flexible ureterorenoscopies
      utilizing reusable (Flex-X2S, Flex-XC, Karl Storz) and 68 applying single-use
      flexible ureterorenoscopes (LithoVue, Boston Scientific) were collected. Clinical
      outcome parameters such as overall success rate, complication rates according to
      Clavien-Dindo, operation time and radiation exposure time were measured. Cost
      analysis was based on purchase costs and recurrent costs for repair and
      reprocessing divided by number of procedures. In each group 68 procedures were
      available for evaluation. In 91% of reusable and 88% of single-use
      ureterorenoscopies stone disease was treated with a mean stone burden of 101 +/-
      226 and 90 +/- 244 mm2 and lower pole involvement in 47 and 41%, respectively (p
      > 0.05). Comparing clinical outcomes of reusable vs. single-use instruments
      revealed no significant difference for overall success rates (81 vs. 87%), stone
      free rates (82 vs. 85%), operation time (76.2 +/- 46.8 vs. 76.8 +/- 40.2 min),
      radiation exposure time (3.83 +/- 3.15 vs. 3.93 +/- 4.43 min) and complication
      rates (7 vs. 17%) (p > 0.05). A wide range of repair and purchase costs resulted
      in total to $1212-$1743 per procedure for reusable ureterorenoscopy whereas price
      of single-use ureterorenoscopy was $1300-$3180 per procedure. The current work
      provided evidence for equal clinical effectiveness of reusable and single-use
      flexible ureterorenoscopes. Partially overlapping ranges of costs for single-use
      and reusable scopes stress the importance to precisely know the expenses and
      caseload when negotiating purchase prices, repair prices and warranty conditions.

PMID- 29356874
TI  - In vitro feasibility of next generation non-linear beamforming ultrasound methods
      to characterize and size kidney stones.
AB  - Ultrasound imaging for kidney stones suffers from poorer sensitivity, diminished
      specificity, and overestimation of stone size compared to computed tomography
      (CT). The purpose of this study was to demonstrate in vitro feasibility of novel
      ultrasound imaging methods comparing traditional B-mode to advanced beamforming
      techniques including plane wave synthetic focusing (PWSF), short-lag spatial
      coherence (SLSC) imaging, mid-lag spatial coherence (MLSC) imaging with
      incoherent compounding, and aperture domain model image reconstruction (ADMIRE).
      The ultrasound techniques were evaluated using a research-based ultrasound system
      applied to an in vitro kidney stone model at 4 and 8 cm depths. Stone diameter
      sizing and stone contrast were compared among the different techniques. Analysis
      of variance was used to analyze the differences among group means, with p < 0.05
      considered significant, and a Student's t test was used to compare each method
      with B-mode, with p < 0.0025 considered significant. All stones were detectable
      with each method. MLSC performed best with stone sizing and stone contrast
      compared to B-mode. On average, B-mode sizing error +/- SD was > 1 mm (1.2 +/-
      1.1 mm), while those for PWSF, ADMIRE, and MLSC were < 1 mm (- 0.3 +/- 2.9 mm,
      0.6 +/- 0.8, 0.8 +/- 0.8, respectively). Subjectively, MLSC appeared to suppress
      the entire background thus highlighting only the stone. The ADMIRE and SLSC
      techniques appeared to highlight the stone shadow relative to the background. The
      detection and sizing of stones in vitro are feasible with advanced beamforming
      methods with ultrasound. Future work will include imaging stones at greater
      depths and evaluating the performance of these methods in human stone formers.

PMID- 29356875
TI  - Upper metastable limit osmolality of urine as a predictor of kidney stone
      formation in children.
AB  - High fluid intake has been universally recommended for kidney stone prophylaxis.
      We evaluated 24-h urine osmolality regarded as the best biomarker of optimal
      hydration and upper metastable limit osmolality after water evaporation from
      urine sample to the onset of spontaneous crystallization and its usefulness as a
      new risk index that would describe an individual lithogenic potential. We
      collected 24-h urine from 257 pediatric patients with kidney stones and 270
      controls. After volume and osmolality assessment, the urine samples were
      subjected to volume reduction in vacuum rotavapor continued to the onset of an
      induced urinary crystallization. The upper metastable limit osmolality of urine
      sample was calculated based on its initial osmolality value and the amount of
      water reduction. Pediatric stone formers presented with higher urine volume and
      lower urine osmolality than healthy controls. Despite that, their urine samples
      required much lower volume reduction to induce the spontaneous crystallization
      than those of controls. The ROC analysis revealed an AUC for the upper metastable
      limit osmolality of 0.9300 (95% CI 0.9104-0.9496) for distinguishing between
      stone formers and healthy subjects. At the cutoff of 2696 mOsm/kg, the test
      provided sensitivity and specificity of 0.8638 and 0.8189, respectively. 24-h
      urine osmolality provided the information about current hydration status, whereas
      evaporation test estimated the urinary potential to crystalize dependent on urine
      composition. Upper metastable limit osmolality may estimate the individual
      lithogenic capability and identify people at risk to stone formation when exposed
      to dehydration.

PMID- 29356876
TI  - Safety of percutaneous nephrolithotomy in patients on chronic anticoagulant or
      antiplatelet therapy.
AB  - In developed countries, the incidence of cardiovascular disease is increasing,
      therefore, anticoagulant and antiplatelet drugs are a widespread treatment
      nowadays. Percutaneous nephrolithotomy (PNL) is the first-line treatment for
      large or complex stones (> 2 cm) and remains an alternative for the smaller ones.
      The objective of this study is to analyze whether PNL surgery is a safe procedure
      in patients under a treatment discontinuation protocol for anticoagulant or
      antiplatelet therapies. We retrospectively studied 301 patients who underwent PNL
      in our hospital between 2008 and 2016 and identified 46 patients on chronic
      antiplatelet or anticoagulation treatment. With respect to PNL outcomes, the
      stone-free rate was similar (78 vs 74%, p = 0.762) in both groups, without any
      significant differences in the overall postoperative complications (17 vs 26%, p
      = 0.203). The incidence of hemorrhagic complications was similar between groups
      (12 vs 9%, p = 0.492), as demonstrated by the mean drop in hemoglobin (Hb), which
      was comparable in both cohorts (2.2 +/- 1.3 vs 2.0 +/- 1.4 p = 0.270) and the
      blood transfusion rate (14% in group A and 8% in group B, p = 0.205). No
      thromboembolic events were found within the year after the PNL procedure. PNL is
      a safe and effective intervention in patients under a treatment discontinuation
      protocol for anticoagulant or antiplatelet therapies. Although our study
      demonstrates the feasibility of this protocol, new scientific evidence aims to
      stratify the thromboembolic and bleeding risk of each patient to individualize
      the perioperative management thereafter.

PMID- 29356877
TI  - Cervical Cancer Induction Enhancement Potential of Chlamydia Trachomatis: A
      Systematic Review.
AB  - Human papillomavirus (HPV) persistent infection is the necessary but not
      sufficient cause of cervical cancer. Other co-factors are required to induce cell
      transformation that will evolve to malignant cervical cancer. These co-factors
      include physical elements, other sexually transmitted infections, and immune
      response. Chlamydia trachomatis the most common bacterial sexually transmitted
      infection is often asymptomatic but causes various syndromes such as cervicitis,
      endometritis, pelvic inflammatory disease, and infertility. It is established
      that this bacterium is involved in cell proliferation process and inhibit
      apoptosis. Furthermore, C. trachomatis may induce chronic inflammation, interfere
      with immune response by decreasing the number of antigen presenting cells, and
      reduce the cell-mediated immunity allowing the persistence of HPV. However, it is
      unclear whether this bacterium plays a particular role in cervical cancer
      induction. We therefore aimed at enlightening the actual knowledge about the
      relationship between C. trachomatis and cervical cancer or precursor lesions
      through a systematic literature review. We summarized and analyzed the
      epidemiological data on C. trachomatis and its co-infection with HPV and their
      association to cervical cancer.

PMID- 29356878
TI  - Complete Genome Sequence of Pseudomonas Parafulva PRS09-11288, a Biocontrol
      Strain Produces the Antibiotic Phenazine-1-carboxylic Acid.
AB  - Rhizoctonia solani is a plant pathogenic fungus, which can infect a wide range of
      economic crops including rice. In this case, biological control of this pathogen
      is one of the fundmental way to effectively control this pathogen. The
      Pseudomonas parafulva strain PRS09-11288 was isolated from rice rhizosphere and
      shows biocontrol ability against R. solani. Here, we analyzed the P. parafulva
      genome, which is ~ 4.7 Mb, with 4310 coding sequences, 76 tRNAs, and 7 rRNAs.
      Genome analysis identified a phenazine biosynthetic pathway, which can produce
      antibiotic phenazine-1-carboxylic acid (PCA). This compound is responsible for
      biocontrol ability against R. solani Kuhn, which is one of the most serious
      fungus disease on rice. Analysis of the phenazine biosynthesis gene mutant,
      DeltaphzF, which is very important in this pathway, confirmed the relationship
      between the pathway and PCA production using LC-MS profiles. The annotated full
      genome sequence of this strain sheds light on the role of P. parafulva PRS09
      11288 as a biocontrol bacterium.

PMID- 29356879
TI  - New ultrasonographic evaluation of stool and/or gas distribution for treatment of
      chronic constipation.
AB  - PURPOSE: The first aim of this study was to develop a new ultrasonographic method
      (US) to evaluate stool and/or gas distribution. The second aim was to apply this
      method to compare stool and/or gas distribution between healthy subjects and
      patients with chronic constipation and evaluate whether US parameters could be an
      alternative to the colonic transit time (CTT). METHODS: We enrolled seven healthy
      volunteers (four men, three women; mean age 29.3 +/- 5.2 years) who underwent US
      and computed tomography (CT) on the same day to evaluate the reproducibility of
      US results. We then enrolled 268 patients with chronic constipation (94 men, 174
      women; mean age 63.3 +/- 4.2 years) and 66 age- and sex-matched healthy subjects
      (controls). The transverse diameters of four segments of the colon [ascending
      (AC), transverse (TC), descending (DC), and sigmoid (SC)] and the rectum (R) were
      measured, and their stool and/or gas distribution was evaluated using the
      constipation index (CI) [AC + TC + DC + SC + R/5] and left/right (L/R)
      distribution [(DC + SC)/(AC + TC)]. The CTT was assessed using radiopaque
      markers. RESULTS: All healthy subjects underwent US and CT successfully, with a
      sufficiently high reproducibility coefficient for this method and significant
      correlation between the US and CT parameters. The stool and/or gas distribution
      evaluated by US showed a significant difference in one of the US parameters
      between healthy subjects and patients, and the CI was an indirect indicator for
      the CTT. CONCLUSIONS: These findings may assist physicians evaluate stool and/or
      gas distribution of patients with chronic constipation, which is an indirect
      indicator for CTT.

PMID- 29356880
TI  - Anesthesia Technique for Cosmetic Breast Augmentation: Does One Size Fit All?

PMID- 29356881
TI  - Temporal changes in outcomes of women and men undergoing percutaneous coronary
      intervention for chronic total occlusion: 2005-2013.
AB  - OBJECTIVE: Percutaneous coronary intervention (PCI) for chronic total occlusion
      (CTO) has undergone impressive progress during the last decade, both in
      strategies and equipment. It is unknown whether technical refinement has
      translated into improved outcomes in women undergoing CTO-PCI. METHOD AND
      RESULTS: A total of 2002 consecutive patients (17% females, mean age 65.2 +/-
      10.7 years) undergoing PCI of at least one CTO lesion at our center between
      01/2005 and 12/2013 were evaluated. The incidence of adverse events was compared
      between two time series (2005-2009 and 2010-2013). A significant increase in
      adverse lesion characteristics over time was noted in both, women and men (p <
      0.001), while technical success rates significantly increased in men but not in
      women (ptrend < 0.001 in men and ptrend=0.9 in women). The incidence of
      procedural complications was significantly higher in women as compared to men and
      increased over the study period in women (p < 0.05) but not in men. Accordingly,
      multivariate logistic regression analysis identified female sex as a strong
      predictor of PCI-related complications in recent years, while this was not the
      case in earlier years (adjusted HR 2.03, 95% CI 0.62-6.6, p = 0.2 and adjusted HR
      4.7, 95% CI 1.8-12.3, p = 0.002, respectively, p < 0.001 for log LH ratio). In
      addition, major adverse cardiovascular events (MACE) after a 3-year follow-up
      significantly declined in men (log rank = 0.046), while no changes were observed
      in women. CONCLUSION: While higher success rates and a reduced rate of MACE have
      been achieved in men, the incidence of procedural complications in women
      undergoing CTO-PCI has increased over time.

PMID- 29356882
TI  - Spanish transcultural adaptation and validation of the English version of the
      compliance questionnaire in rheumatology.
AB  - To perform a transcultural adaptation and validation of a Spanish version of the
      compliance questionnaire in rheumatology (sCQR). In this transversal study of
      transcultural adaptation of the sCQR, validity was evaluated in patients with
      rheumatoid arthritis (RA) and a minimum 6-month follow-up by determining
      compliance with the electronic prescription system in consuming steroids or
      nonbiologic disease-modifying antirheumatic drugs. A two-week retest was proposed
      to all patients. All patients completed the health assessment questionnaire
      (HAQ), and the Morisky-Green test was also performed. Reliability was analyzed
      using Cronbach's alpha and the intraclass correlation coefficient (ICC).
      Convergent construct validity was tested in the electronic prescription system
      using discriminative analysis, and divergent construct validity was tested by
      comparing it to the HAQ. Sensitivity, specificity and ROC curves were evaluated
      for the sCQR and the Morisky-Green test. Of 123 recruited patients, 101 fulfilled
      the inclusion criteria, and 61 were on biologic therapy. 23 performed the retest.
      Test-retest reliability (ICC) was 0.76 (Cronbach's alpha 0.86). Multiple
      regression analysis showed correlation with each item of the sCQR as independent
      variables (r2 = 0.60). No correlation was seen between total score punctuation of
      the sCQR and the HAQ (r2 = 0.22). Discriminative analysis weighting each sCQR
      item showed a cutoff point of - 0.9991 (sensibility and 58.8%, specificity
      98.3%). The likelihood ratio of the sCQR to detect <= 80% adherence with
      electronic prescriptions was 35.3. The Morisky-Green test revealed sensibility
      and specificity were 29.4 and 83.3%, respectively. This study validates the
      transcultural adaptation of sCQR in RA patients. A high reliability of sCQR for
      measuring adherence was found. Its predictive value suggests that it could be
      used as a screening instrument.

PMID- 29356883
TI  - Evaluation of ITGB2 (CD18) and SELL (CD62L) genes expression and methylation of
      ITGB2 promoter region in patients with systemic sclerosis.
AB  - Systemic sclerosis (SSc), an autoimmune disease of connective tissue, is
      characterized by inflammation, fibrosis, and vessel endothelial damage. Products
      of Integrin subunit beta 2 (ITGB2) and selectin L (SELL) genes participate in
      several functional pathways of immune system. The aim of this investigation was
      to survey the transcript level of ITGB2 and SELL genes as well as methylation
      status of CpG sites in promoter region of differently expressed gene in PBMCs of
      SSc patients. PBMCs were isolated from whole blood of 50 SSc patients and 30
      healthy controls. Total RNA and DNA contents of PBMCs were extracted. Gene
      expression was analyzed by real-time PCR using the SYBR Green PCR Master Mix. To
      investigate the methylation status of CpG sites, DNA samples were treated by
      bisulfite, amplified through nested PCR, and sequenced through Sanger difficult
      sequencing method. ITGB2 gene in PBMCs of SSc patients was overexpressed
      significantly in comparison to healthy controls. However, no altered SELL
      expression was observed. Three CpG sites of 12, 13 and 14 were significantly
      hypomethylated in patients group, despite overall methylation status of ITGB2
      gene promoter revealed no significant difference between study groups. There was
      no statistically significant correlation between methylation status of ITGB2
      promoter and the gene expression in patients. Regarding to lack of correlation of
      increased expression of ITGB2 with its promoter hypomethylation in SSc patients,
      our study suggests that upregulation of ITGB2 in PBMCs from SSc patients is
      probably due to another mechanism other than methylation alteration.

PMID- 29356884
TI  - Correction to: Impacts and Policy Implications of Metals Effluent Discharge into
      Rivers within Industrial Zones: A Sub-Saharan Perspective from Ethiopia.
AB  - The original version of this article unfortunately contained mistakes in the
      Tables (1 and 2) caption and article title is updated.

PMID- 29356886
TI  - The XEN45 Gel Stent as a minimally invasive procedure in glaucoma surgery:
      success rates, risk profile, and rates of re-surgery after 261 surgeries.
AB  - PURPOSE: The XEN45 Gel Stent is a flexible hydrophilic tube placed under the
      conjunctiva via the anterior chamber. This study investigates the IOP
      (intraocular pressure)-lowering potential, the risk profile, and the success rate
      of the XEN45 Gel Stent. METHODS: Two hundred and sixty-one eyes underwent
      surgery. The mean follow-up time was 8.5 months. The aim of the treatment was to
      achieve adequate IOP reduction without medication. Therefore, all patients who
      did not show sufficiently reduced IOP underwent a surgical revision with opening
      of the conjunctiva. To determinate the success rate, we carried out two kinds of
      analysis: 1) the primary success rate: eyes with appropiate IOP control without
      medication or surgical revision, and 2) overall success rate: one surgical
      revision was allowed. RESULTS: Intraocular pressure was lowered from 24.3 mmHg
      (SD 6.6) to 16.8 mmHg (SD 7.6), and the medication score was lowered from 2.6 (SD
      1.1) to 0.2 (SD 0.7). Revisional surgery was performed in 80 eyes (34%). After a
      first revision, intraocular pressure was lowered to 14.0 mmHg (SD 5.1), and the
      medication score was lowered to 0.2 (SD 0.6). The primary success rate was 66%
      and the overall success rate 90%. The primary success rate was higher in
      pseudophakic eyes (73%) than in phakic eyes (53%) or combined surgery (55%).
      CONCLUSIONS: We conclude from our data that the XEN45 Gel Stent has an IOP
      lowering potential and few side-effects. Pseudophakic eyes seem to have a better
      primary prognosis compared to combined surgery or surgery in phakic eyes.

PMID- 29356888
TI  - The use of complementary and alternative medicine by patients in routine care and
      the risk of interactions.
AB  - BACKGROUND: Patients suffering from cancer often make use of complementary and
      alternative medicine (CAM). Only few data exist on the prevalence and clinical
      significance of interactions of a biological CAM method and conventional drugs.
      METHODS: From February 2014 to March 2016, consecutive patients from five
      oncological practices in Germany were asked to fulfill a standardized
      questionnaire regarding use of CAM. Data on diagnosis, date of first diagnosis,
      ECOG and the past and current treatment were derived from the patients' files.
      Interactions were evaluated by systematically using a database on potential
      interactions. RESULTS: From 1000 patients asked to participate, we received a
      total of 720 questionnaires of which 711 were completed and eligible for
      evaluation. 29% of the patients reported any CAM usage. Women showed a
      significantly higher use of CAM with 35.6 versus 23.6% of men. For 54.9% of CAM
      users (15.9% of all patients), we found a combination of conventional drugs and
      biological based CAM methods with a risk for interactions. Vitamins A, C and E
      were the most frequently used CAM substances in these cases (39.3%), followed by
      herbs with 17.5%. CONCLUSION: There was a risk of interactions between a
      biological CAM method and conventional drugs in 54.9% of the patients using CAM.
      To raise knowledge on interactions a better training for doctors with respect to
      CAM is strongly needed. Furthermore, patients' awareness should also be raised
      and communication between physician and patient on the topic improved.

PMID- 29356887
TI  - Risk for cancer in living kidney donors and recipients.
AB  - OBJECTIVE: Malignancy following renal transplantation remains inconsistent with
      the reported safety of kidney donation during the long-term follow-up. METHODS:
      We conducted searches of the published literature which included healthy
      participants, recipients, living kidney donors (LKDs), and the availability of
      outcome data for malignancy. Eight from 938 potentially relevant studies were
      analyzed by means of fixed-effects model or random-effects model, as
      appropriately. RESULTS: In 48,950 participants, the follow-up range was 18 months
      to 20 years, and the mean age of the subjects was approximately 41 years. The
      incidence rate with 95% confidence interval (CI) for malignancy after kidney
      transplantation was 0.03 (0.01-0.05) in recipients and 0.03 (0.1-0.07) in LKDs,
      giving a pooled incidence rate of 0.03 (95% CI 0.02-0.04). LKDs contrasted
      nondonors by the overall odds ratio and 95% CI for total cancer of 2.80 (2.69
      2.92). CONCLUSIONS: Kidney transplantation was associated with an increased risk
      of cancer during a long-term follow-up. Long-term risk for cancer in LKDs and
      kidney recipients should be monitored.

PMID- 29356889
TI  - National changes in pediatric tracheotomy epidemiology during 36 years.
AB  - BACKGROUND: Information on the incidence, indications and morbidity of pediatric
      tracheotomy from a nationwide setting is sparse. METHODS: From the nationwide
      Danish National Patient Registry, we identified all cases: 0-15-year-old children
      registered with a first-time tracheotomy from 1979 to 2014. We extracted the date
      of surgery, admission, discharge, age, gender, hospital, department,
      hospitalization length, hospital contacts, and diagnosis-code related to the
      surgery. We estimated age-adjusted incidence rates (AAIR) and annual (APC) and
      average annual percentage change (AAPC) of tracheotomy incidence. RESULTS: A
      total of 510 children (328 boys, 63%) underwent tracheotomy. The median age at
      surgery was 8 years. The AAIR was 1.4/100,000 person-years (range 1.0-1.8) from
      1980 to 2014. During 1979-2014, the AAPC decreased - 0.9% (95% confidential
      interval - 2.4; 0.8, p < 0.3). From 1979 to 2003 the APC decreased - 4.1% (95% CI
      - 5.4; - 2.8, p < 0.001) and from 2003 to 2014 the APC increased 6.6% (95% CI
      2.0; 11.5, p < 0.001). Infants had the highest incidence (4.0/100,000 years)
      compared with the 12-15-year-olds (AAIR: 0.4/100,000 years). From 1979 to 2014
      the most common indication for tracheotomy among children aged 0-2 years was
      congenital malformations (n = 48, 30%) and among children aged 3-11 and 12-15
      years the most common indication was trauma (respectively n = 67, 36% and n = 85,
      52%). During 2006-2014 the most common indications for all ages was neurological
      impairment (n = 25, 21%) and neoplasms (n = 20, 17%). CONCLUSIONS: Pediatric
      tracheotomy was a rare surgical procedure with decreasing incidence rates from
      1980-89 to 1990-99 and increasing incidence rates from 2000-2009 to 2010-2014.
      Indications and postoperative morbidity have changed adjunct to the treatment of
      chronic disorders.

PMID- 29356890
TI  - Patterns of care and impact of prognostic factors in the outcome of NUT midline
      carcinoma: a systematic review and individual patient data analysis of 119 cases.
AB  - INTRODUCTION: NUT midline carcinoma is a rare tumour occurring in young adults
      which is frequently misdiagnosed as poorly differentiated squamous cell carcinoma
      or germ cell tumour. Though considered highly aggressive, there is limited
      information about the clinical behaviour of such patients. We intended to perform
      this review of published literature to assess the demographic profile, pattern of
      care and assess survival outcomes. METHODS: Two authors independently searched
      PubMed and Google search for eligible studies from 1950 till July 1 2017
      published in English language using MESH terms NUT midline carcinoma; NUT midline
      carcinoma and radiotherapy and translocation 15:19 tumour. RESULTS: Data of 119
      patients were retrieved from 64 publications for statistical analysis. Median age
      of the entire cohort was 23 years (range 0-68 years). The analysis revealed equal
      incidence in males and females (60:58). The present analysis revealed that the
      most common location is the lung (n = 42) followed by head and neck (n = 40).
      Median OS for the entire cohort was only 5 months with 1 and 5 year OS for the
      entire cohort was 24.99 and 7.09% respectively. Radiotherapy and chemotherapy
      inclusion in primary treatment had a significant impact on overall survival on
      univariate analysis while surgery did not affect survival significantly. No
      impact on overall survival was found based on type of molecular translocation,
      i.e., NUT-BRD4, NUT-BRD3 or other variants. Inadequate data were available for
      identify impact of BET inhibitors and HiDAc on PFS and OS. CONCLUSION: NUT
      midline carcinoma has dismal prognosis. Radiotherapy and chemotherapy improves
      survival, but do not provide long term control except in anecdotal cases. Further
      research is needed to improve outcomes in future.

PMID- 29356891
TI  - High immune cell score predicts improved survival in pancreatic cancer.
AB  - Increasing evidence suggests that cancer progression is strongly influenced by
      host immune response, which is represented by immune cell infiltrates. T
      lymphocyte-based immunoscore has proved to be a prognostic factor in colon
      cancer, but its significance in pancreatic cancer is poorly known. Total of 108
      patients operated (R0/R1) for pancreatic ductal adenocarcinoma (PDAC) (TNM stage
      I-II) were included in the study. Immune cell score (IS) was determined by
      scoring the samples from grade 0 to 4 according to the number of immune cells
      (CD3+ and CD8+) in tumor core and invasion margin using tissue microarrays,
      immunohistochemistry, and digital analysis. Tumors with microsatellite
      instability were identified by MLH1 immunostaining. High IS and low histological
      grade were significantly associated with better disease-specific survival (DSS)
      and overall survival (OS). The 5-year DSS rate for low, moderate, and high IS
      groups were 5.0, 15.2, and 33.4%, respectively (p = 0.007). The 5-year OS rate
      for the low, moderate, and high IS groups were 4.2, 13.4, and 31.5%, respectively
      (p = 0.004). In addition, IS and prognosis varied within a single TNM stage.
      There was no association between IS and any of the clinicopathological variables.
      IS was shown to be an independent prognostic factor for better DSS and OS in
      multivariate analysis, together with the histological grade of the tumor and
      perineural invasion. Five MLH1-negative tumors (4.6%) were found showing no
      correlation with IS. IS could be a useful prognostic marker in patients with PDAC
      treated by primary surgery.

PMID- 29356892
TI  - Skin depigmenting action of silkworm (Bombyx mori L.) droppings in zebrafish.
AB  - The excrement of silkworms (Bombyx mori L.), referred to here as silkworm
      droppings (SDs), is used as a traditional drug in eastern medicine to treat skin
      diseases such as urticaria and atopy. However, the depigmentation effects of SDs
      have not previously been evaluated. We focused on the depigmentation effect of a
      methanol extract of SDs and isolated components of the extract using a zebrafish
      model system. (+)-Dehydrovomifoliol (M-1), (6R,7E,9R)-9-hydroxy-4,7
      megastigmadien-3-one (M-2), (3S,5R,8R)-3,5-dihydroxymegastigma-6,7-dien-9-one (M
      3), roseoside (M-4), and citroside A (M-5) were isolated from only SDs extract
      (SDE), and chemical structures were identified through spectroscopic methods.
      Toxicity of SDE was evaluated by assessing its effect on the viability of human
      fibroblast cells and the hatching rate of zebrafish embryos. In addition, the
      depigmentation ability of SDE and isolated constituents was evaluated using a
      zebrafish model. Binary threshold, histograms, and the size of the black spots on
      the dorsal region of zebrafish larvae were analyzed using image analysis tools.
      Finally, SDE is a non-toxic material and has a dose-dependent depigmentation
      effect in zebrafish larvae. Moreover, various doses of compounds isolated from
      SDE, namely, M-1 to M-5, had a depigmentation effect. In particular, M-5
      inhibited melanin synthesis in melanocytes stimulated by alpha-melanocyte
      stimulating hormone (alpha-MSH). Together, our results suggest that SDs can be
      used for depigmentation purposes in health and/or cosmetic applications.

PMID- 29356893
TI  - Attentional control transfers beyond the reference frame.
AB  - Much research has shown that humans can allocate attentional control
      differentially to multiple locations based on the amount of conflict historically
      associated with a given location. Additionally, once established, these control
      settings can transfer to nearby locations that themselves have no conflict bias.
      Here we examined if these control settings also extend to nearby locations that
      are presented outside of the original frame of reference of biased stimuli.
      During training, participants first responded to biased flanker stimuli that were
      likely high conflict in one location and low conflict in another location. Then
      they were exposed to two sets of unbiased stimuli presented in novel transfer
      locations outside of the established reference frame of biased stimuli. Across
      three experiments, attentional control settings transferred beyond the reference
      frame including when there was a visual border (Experiment 2) or meaningful
      categorical distinction (Experiment 3) delineating training and transfer
      locations. These novel findings further support the idea that stimulus-driven
      attention control can be flexibly allocated, perhaps in a categorical manner.

PMID- 29356894
TI  - Development of Thinopyrum ponticum-specific molecular markers and FISH probes
      based on SLAF-seq technology.
AB  - MAIN CONCLUSION: Based on SLAF-seq, 67 Thinopyrum ponticum-specific markers and
      eight Th. ponticum-specific FISH probes were developed, and these markers and
      probes could be used for detection of alien chromatin in a wheat background.
      Decaploid Thinopyrum ponticum (2n = 10x = 70) is a valuable gene reservoir for
      wheat improvement. Identification of Th. ponticum introgression would facilitate
      its transfer into diverse wheat genetic backgrounds and its practical utilization
      in wheat improvement. Based on specific-locus-amplified fragment sequencing (SLAF
      seq) technology, 67 new Th. ponticum-specific molecular markers and eight Th.
      ponticum-specific fluorescence in situ hybridization (FISH) probes have been
      developed from a tiny wheat-Th. ponticum translocation line. These newly
      developed molecular markers allowed the detection of Th. ponticum DNA in a
      variety of materials specifically and steadily at high throughput. According to
      the hybridization signal pattern, the eight Th. ponticum-specific probes could be
      divided into two groups. The first group including five dispersed repetitive
      sequence probes could identify Th. ponticum chromatin more sensitively and
      accurately than genomic in situ hybridization (GISH). Whereas the second group
      having three tandem repetitive sequence probes enabled the discrimination of Th.
      ponticum chromosomes together with another clone pAs1 in wheat-Th. ponticum
      partial amphiploid Xiaoyan 68.

PMID- 29356895
TI  - Management of spinal infection: a review of the literature.
AB  - Spinal infection (SI) is defined as an infectious disease affecting the vertebral
      body, the intervertebral disc, and/or adjacent paraspinal tissue and represents 2
      7% of all musculoskeletal infections. There are numerous factors, which may
      facilitate the development of SI including not only advanced patient age and
      comorbidities but also spinal surgery. Due to the low specificity of signs, the
      delay in diagnosis of SI remains an important issue and poor outcome is
      frequently seen. Diagnosis should always be supported by clinical, laboratory,
      and imaging findings, magnetic resonance imaging (MRI) remaining the most
      reliable method. Management of SI depends on the location of the infection (i.e.,
      intraspinal, intervertebral, paraspinal), on the disease progression, and of
      course on the patient's general condition, considering age and comorbidities.
      Conservative treatment mostly is reasonable in early stages with no or minor
      neurologic deficits and in case of severe comorbidities, which limit surgical
      options. Nevertheless, solely medical treatment often fails. Therefore, in case
      of doubt, surgical treatment should be considered. The final result in
      conservative as well as in surgical treatment always is bony fusion. Furthermore,
      both options require a concomitant antimicrobial therapy, initially applied
      intravenously and administered orally thereafter. The optimal duration of
      antibiotic therapy remains controversial, but should never undercut 6 weeks. Due
      to a heterogeneous and often comorbid patient population and the wide variety of
      treatment options, no generally applicable guidelines for SI exist and management
      remains a challenge. Thus, future prospective randomized trials are necessary to
      substantiate treatment strategies.

PMID- 29356896
TI  - The search for attitude-a hidden curriculum assessment from a central European
      perspective.
AB  - BACKGROUND: Little is known about the development of the hidden curriculum in the
      medical education system. It refers to a conglomeration of implicit beliefs,
      attitudes and forms of conduct that are unwittingly transmitted from one
      generation of teaching physicians to the next. How can we describe this process,
      what are the potential positive or negative impacts, and last but not least, how
      can we measure it? METHODS: Students of the Medical University of Vienna complete
      their clinical rotations in Vienna and in other accredited, mostly central
      European hospitals. They were subsequently invited to evaluate their rotations in
      an online questionnaire regarding dimensions, such as professionalism, teaching,
      integration and appreciation. RESULTS: In total, 133 students participated in
      this pilot study and the average response rate was 10.1%, similar to evaluations
      conducted prior to that. Although the evaluation results on average were
      positive, several experiences of deprecation and less professional conduct were
      present in each evaluated rotation. Giving the students the opportunity to
      reflect upon their experiences could be seen as an intervention and investigation
      at the same time. CONCLUSIONS: This survey serves as a precursor to a qualitative
      interview-based study, accompanying the implementation of case-based learning
      designed by collaborating residents and medical students. The findings of this
      pilot-study support the necessity of fostering a reflective capacity in the
      education of medical students, enabling them to speak up and live up to the
      expected professionalism despite shortcomings within the hidden curriculum.

PMID- 29356898
TI  - Vitamin D pathway gene polymorphisms and hepatocellular carcinoma in chronic
      hepatitis C-affected patients treated with new drugs.
AB  - PURPOSE: Since HCV infection may lead to hepatocellular carcinoma (HCC) and
      vitamin D (deficiency) is related to cancer, we investigated if SNPs in genes
      involved in vitamin D pathway could predict HCV-related HCC presence in patients
      treated with new anti-HCV drugs. METHODS: Patients with chronic hepatitis C and
      treated with direct-acting antivirals were enrolled. SNPs in VDR, CYP27B1,
      CYP24A1 and GC genes were assessed through real-time PCR. 258 patients were
      analyzed. RESULTS: HCC was present in six patients, all taking sofosbuvir, all
      males and five/six had cirrhosis. HCV-RNA log levels at baseline were
      statistically different between patients with and without HCC. VDR FokI T > C SNP
      resulted associated with HCC: all the CC patients were free from HCC. An
      association between HCC presence and undetectable HCV-RNA at 1 month of therapy
      was suggested; cirrhosis was related to HCC. HCC risk factors were age, ribavirin
      administration, IL28Brs12979860CC and previous treatments; VDR FokICC, sex and
      insulin resistance were protective factors. CONCLUSIONS: These data highlighted
      vitamin D pathway gene SNPs and HCC relationship in the Italian population;
      further studies are required.

PMID- 29356897
TI  - Inter-individual variation in adaptations to endurance and resistance exercise
      training: genetic approaches towards understanding a complex phenotype.
AB  - Exercise training which meets the recommendations set by the National Physical
      Activity Guidelines ensues a multitude of health benefits towards the prevention
      and treatment of various chronic diseases. However, not all individuals respond
      well to exercise training. That is, some individuals have no response, while
      others respond poorly. Genetic background is known to contribute to the inter
      individual (human) and -strain (e.g., mice, rats) variation with acute exercise
      and exercise training, though to date, no specific genetic factors have been
      identified that explain the differential responses to exercise. In this review,
      we provide an overview of studies in human and animal models that have shown a
      significant contribution of genetics in acute exercise and exercise training
      induced adaptations with standardized endurance and resistance training regimens,
      and further describe the genetic approaches which have been used to demonstrate
      such responses. Finally, our current understanding of the role of genetics and
      exercise is limited primarily to the nuclear genome, while only a limited focus
      has been given to a potential role of the mitochondrial genome and its
      interactions with the nuclear genome to predict the exercise training-induced
      phenotype(s) responses. We therefore discuss the mitochondrial genome and
      literature that suggests it may play a significant role, particularly through
      interactions with the nuclear genome, in the inherent ability to respond to
      exercise.

PMID- 29356900
TI  - Structural insights on bioremediation of polycyclic aromatic hydrocarbons using
      microalgae: a modelling-based computational study.
AB  - Research on bioremediation of polycyclic aromatic hydrocarbons (PAHs) has
      established that several remediating microbial species are capable of degrading
      only low molecular weight (LMW)-PAHs, whereas high molecular weight (HMW)-PAHs
      are hardly degradable. In the present study, the efficiency of degradation of
      both LMW and HMW-PAHs by cytochrome P450 monooxygenase (CYP) of microalgae was
      studied. CYP have a key role in the detoxification of xenobiotics. So far, the
      structure of CYP in microalgae is not predicted; the protein structure was
      constructed by molecular modelling in the current study using the available
      template of microalgal CYP. Modelled microalgae 3D structures were docked against
      38 different PAH compounds, and the information regarding the interaction between
      protein and PAHs viz. binding sites along with mode of interactions was
      investigated. We report that CYP from the microalgae Haematococcus pluvialis and
      Parachlorella kessleri was found to possess broad oxidising capability towards
      both LMW and HMW-PAHs. P. kessleri showed a least value with extra precision
      glide score of - 10.23 and glide energy of - 23.48 kcal/mol. PAHs bind to CYP
      active sites at Lys 69, Trp 96, Gln 397 and Arg 398 through intermolecular
      hydrogen bonding. Also, study revealed that PAHs interacted with CYP active sites
      through intermolecular hydrogen bonding, hydrophobic bonding, pi-pi interactions
      and van der waals interactions. Thus, structural elucidation study confirms that
      microalgae Parachlorella kessleri have the capacity to remediate HMW more
      efficiently than other microorganisms. Our results provide a framework in
      understanding the structure and the possible binding sites of CYP protein for
      degradation of PAH and that could be a screening tool in identifying the
      phycoremediation potential.

PMID- 29356899
TI  - Mindfulness vs psychoeducation in adult ADHD: a randomized controlled trial.
AB  - BACKGROUND: Mindfulness training is a promising treatment approach in adult ADHD.
      However, there has not yet been a randomized controlled trial comparing
      mindfulness to an active control condition. In this study, we assessed the
      efficacy of a mindfulness training program (MAP) compared to structured
      psychoeducation (PE). METHODS: After randomization 81 medication-free adult ADHD
      patients participated either in an 8-week MAP or PE group program. At baseline
      (T1), after 8 weeks (T2) and after 8 months (T3), severity of ADHD and associated
      symptoms (depression, general psychopathology, quality of life) were measured
      with the Conner's ADHD Rating Scales (CAARS), the Beck Depression Inventory
      (BDI), the Brief Symptom Inventory (BSI) and the SF-36 by self and blind observer
      ratings. RESULTS: Both groups showed significant pre-post improvements in
      observer-rated Inattention scale (p < .001, partial eta2 = 0.18) and in
      associated symptomatology, which persisted through 6 months of follow-up. There
      were no significant differences regarding symptom reduction between the treatment
      groups. Women benefited more compared to men irrespective of treatment group. Men
      showed the most pronounced changes under MAP. CONCLUSIONS: In the current study,
      MAP was not superior to PE regarding symptom reduction in adult ADHD. Both
      interventions, mindfulness meditation and PE, were efficacious in reducing
      symptom load in adult ADHD. Furthermore in exploratory post hoc tests the study
      provides evidence for a potential gender-specific treatment response in adult
      ADHD.

PMID- 29356901
TI  - Glycine enhances expression of adiponectin and IL-10 in 3T3-L1 adipocytes without
      affecting adipogenesis and lipolysis.
AB  - Glycine supplementation has been reported to enhance white-fat loss and improve
      sensitivity to insulin in animals with obesity or type 2 diabetes. However, the
      underlying mechanisms responsible for the beneficial effects of glycine remain
      largely unknown. The purpose of this study was to test the hypothesis that
      glycine regulates adipocyte differentiation, adipogenesis, and lipolysis,
      therefore, contributing to white-fat reduction. 3T3-L1 pre-adipocytes were
      induced to differentiate into adipocytes in the presence of glycine (0, 0.25,
      1.0, and 2.0 mmol/L) or resveratrol (50 or 100 MUmol/L, served as a positive
      control) during the differentiation process. Hela and HepG2 cells cultured with
      oleic acid to induce lipid accumulation in the presence of glycine (0, 1.0, and
      2.0 mmol/L) or 10 MUmol/L isoproterenol (served as a positive control) for 24 h.
      Intracellular lipid accumulation, intracellular triglycerides, lipid droplets'
      diameters of mature adipocytes, mRNA, and protein levels of genes involved in the
      adipogenesis and lipolysis were analyzed. Isobutylxanthine-dexamethasone-insulin
      (MDI)-induced adipogenesis in 3T3-L1 cells were blocked by resveratrol, but not
      by glycine, as shown by decreased lipid contents, reduced diameters of lipid
      droplets, decreased protein abundances for peroxisome proliferator-activated
      receptor gamma (PPARgamma), CCAAT-enhancer-binding protein alpha (C/EBPalpha), as
      well as increased protein abundance of peroxisome proliferator-activated receptor
      coactivator-1alpha (PGC-1alpha), critical transcriptional factors that regulates
      adipogenesis. However, the mRNA levels of adiponectin and interleukin-10 (IL-10),
      two adipose-derived adipocytokines with anti-inflammatory effects, were greatly
      enhanced (P < 0.05) by 2 mmol/L glycine. Compared with non-treated controls, 10
      MUmol/L isoproterenol significantly decreased (P < 0.05) the intracellular lipid
      and triglyceride contents induced by oleic acid in Hela and HepG2 cells. mRNA
      level of fatty acid synthase (FASN), a gene involved in fatty acid synthesis, was
      significantly reduced (P < 0.05), while that for ATGL (adipose triglyceride
      lipase) and HSL (hormone-sensitive lipase), genes involved in lipolysis were
      significantly enhanced (P < 0.05) by isoproterenol. However, oleic acid induced
      the accumulation of intracellular triglyceride and lipid contents were not
      affected by glycine. In conclusion, glycine exposure enhanced the mRNA levels of
      adipose-derived adiponectin and IL-10 without affecting adipogenesis and
      lipolysis in 3T3-L1 adipocytes. These findings provide a possible explanation for
      the anti-obesity and anti-diabetic effects of glycine that were previously
      reported in animal models. More studies are needed to uncover the underlying
      mechanisms responsible for this regulatory effect of glycine on anti-inflammatory
      adipocytokines expression in both in vitro and in vivo models.

PMID- 29356902
TI  - The effects of road building on arbuscular mycorrhizal fungal diversity in
      Huangshan Scenic Area.
AB  - Arbuscular mycorrhizal (AM) fungi are vital soil microbes that connect many
      individual plants into a large functional organism via a vast mycelial network
      under the ground. In this study, the changes of soil AM fungal community in
      response to road-building disturbance caused by tourism development in Huangshan
      (Yellow Mountain) Scenic Area are assessed. Road building have brought negative
      effects on AM fungal community, inducing lower diversity parameters, including
      species number, spore density and diversity indices. However, the dominant genus
      and species of AM fungi which play key roles in the AM fungal community
      composition are quite similar before and after road building. Moreover, there are
      no significant differences in species richness of AM fungi associated with
      plants, suggesting the tolerance of AM fungal community to the disturbance of
      road building.

PMID- 29356904
TI  - An orangutan in Paris: pondering Proximity at the Museum d'histoire naturelle in
      1836.
AB  - When the Museum d'histoire naturelle in Paris learned in 1836 that it had the
      chance to buy a live, young orangutan, it was excited by the prospect. Specimens
      were the focus of the Museum's activities, and this particular specimen seemed
      especially promising, not only because the Museum had very few orangutan
      specimens in its collection, but also because of what was perceived to be the
      orangutan's unique place in the natural order of things, namely, at the very
      boundary between the animal kingdom and humans. Frederic Cuvier, the
      superintendent of the Museum's menagerie, urged that studying the orangutan's
      mental faculties would help resolve fundamental questions regarding the
      similarities and differences between animals and humans. Archival and printed
      sources allow one to reconstruct the orangutan's capture, acquisition, and
      subsequent career at the menagerie in greater detail than has generally been
      possible for animals of nineteenth-century zoos. Scientists, artists, the public,
      the press, and even musicians (Franz Liszt included) sought to engage with the
      orangutan, seeing in it not just another ape or monkey but a special creature
      unto itself at the animal/human boundary. Key to their fascination with the
      orangutan was the question of proximity-just how close was the orangutan to
      humans? The orangutan's story illuminates not only how the animal-human boundary
      was conceived at the time but also the problematic status of the zoo as a site
      for scientific research and the roles of scientific and non-scientific actors
      alike in constructing how the orangutan was understood.

PMID- 29356903
TI  - Tubercular retinal vasculitis mimicking frosted branch angiitis: a case report.
AB  - BACKGROUND: Tubercular vasculitis is an important manifestation of ocular
      tuberculosis and this report highlights the mimicking nature of the disease with
      frosted branch angiitis. RESULTS: A patient presented with a severe form of
      retinal vasculitis in both eyes and a branch retinal vein occlusion in the left
      eye. He had a positive tuberculin skin test (TST) and a raised erythrocyte
      sedimentation rate (ESR) and serum angiotensin-converting enzyme (ACE) levels.
      Radiological investigations revealed a sub-pleural nodule and mediastinal lymph
      nodes, which on histopathological evaluation confirmed a granulomatous etiology.
      CONCLUSION: Retinal vasculitis secondary to tubercular etiology may mimic a viral
      vasculitis; however, a clinical suspicion with a timely diagnosis and management
      helps in preventing loss of vision and the eye.

PMID- 29356905
TI  - Actinidia callosa var. callosa suppresses metastatic potential of human hepatoma
      cell SK-Hep1 by inhibiting matrix metalloproteinase-2 through PI3K/Akt and MAPK
      signaling pathways.
AB  - BACKGROUND: Cancer cell metastasis involving multi-step procedures and
      cytophysiological property changes may make difficult in the clinical management
      and death rate increasing. RESULTS: In this study, we first observed that ethyl
      acetate fraction of Actinidia callosa var. callosa (EAAC) carry out a dose
      dependent inhibitory effect without cytotoxicity on the mobility and invasion of
      highly metastatic SK-Hep1 cells. To investigate the EAAC in cancer metastasis, SK
      Hep1 cells were treated with EAAC at various concentrations and then subjected to
      gelatin zymography, casein zymography and western blot to study the impacts of
      EAAC on metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1/2
      (TIMP-1/2), respectively. Our results showed that EAAC treatment may decrease the
      expressions of MMP-2 and enhance the expression of TIMP-1/2 in a concentration
      dependent manner. EAAC also inhibited effect on the phosphorylation of mitogen
      activated protein kinase (MAPK) and phosphatidylinositol-3
      kinase/serine/threonine protein kinase [or protein kinase B (PI3K/Akt)] and focal
      adhesion kinase (FAK). CONCLUSIONS: These results indicate that EAAC inhibited SK
      Hep1 cell of metastasis by reduced protein level of MMP-2 through the suppression
      of MAPK and FAK signaling pathway and of the activity of PI3K/Akt. These findings
      suggest that EAAC may be used as an antimetastatic agent.

PMID- 29356906
TI  - Sialolith removal in the submandibular region using surgical diode laser: report
      of two cases and literature review.
AB  - PURPOSE: Sialolithiasis is defined as the presence of one or more calcified
      structures within the duct of a major or minor salivary gland. It occurs as a
      result of deposition of calcium salts around an accumulation of organic debris in
      the duct lumen. The main signs and symptoms are edema and bacterial infection
      with abscess formation. METHODS: This study aimed to report two cases of
      submandibular sialolithiasis treated surgically with diode laser and conduct a
      review of the literature by means of a systematic search. In the two cases, the
      calculi were located in the distal part of the submandibular duct and could be
      palpated intraorally. Surgery was performed in an outpatient setting under local
      anesthesia. A linear incision was made in the floor of the mouth, in the region
      of the opening of Wharton's duct, to expose and remove the calculi. Laser cutting
      was performed using a diode laser module coupled to a 400-MUm optical fiber
      emitting at a wavelength of 980 nm (infrared), 2.5 W output power, and in
      continuous pulse mode. RESULTS: The use of diode laser is a safe and minimally
      invasive option for this type of procedure. CONCLUSION: Offering advantages such
      as enhanced coagulation properties and high-quality incision, absence of
      bleeding, low risk of nerve damage, and few comorbidities.

PMID- 29356907
TI  - Minimally invasive fixation techniques for thoracolumbar fractures: comparison
      between percutaneous pedicle screw with intermediate screw (PPSIS) and
      percutaneous pedicle screw with kyphoplasty (PPSK).
AB  - PURPOSE: To assess and compare the efficacy of two minimally invasive techniques
      (percutaneous pedicle screw with intermediate screw vs. percutaneous pedicle
      screw with kyphoplasty) for spinal fracture fixation by comparing the segmental
      kyphosis and vertebral kyphosis angles after trauma before surgery, after
      surgery, and at 4-month and 12-month follow-up. METHODS: Data from 49 patients
      without neurological deficit treated by either percutaneous pedicle screw with
      intermediate screw or percutaneous pedicle screw with kyphoplasty were
      retrospectively analysed. The segmental kyphosis and vertebral kyphosis angles
      over time were calculated and correlated with the type of procedure, AO
      classification, lumbar or thoracic site and the age and sex of the patients.
      RESULTS: After surgery, both techniques were found to be efficacious means of
      bringing about a significant correction of the segmental kyphosis angle (p =
      0.002) and a just significant correction of the vertebral kyphosis angle (p =
      0.06), although less effectively in thoracic fractures (p = 0.004). At follow-up,
      the vertebral kyphosis angle was stable in both groups, while there was a
      significant loss of segmental kyphosis angle stability in the percutaneous
      pedicle screw with kyphoplasty group at 1 year (p = 0.004); fractured thoracic
      vertebrae maintained a greater vertebral kyphosis angle (p = 0.06) and segmental
      kyphosis angle (p < 0.001), than the lumbar. CONCLUSION: At 1 year after surgery,
      the use of intermediate screws in fractured vertebrae seemed to maintain a more
      efficacious correction with respect to kyphoplasty, although thoracic fracture
      sites appear to be associated with greater post-traumatic segmental kyphosis and
      lesser stability in the long term after both percutaneous surgical techniques.

PMID- 29356909
TI  - Summary for patients: International guidelines for groin hernia management.

PMID- 29356910
TI  - Comment to: Pre-peritoneal local anaesthetic does not reduce post-operative pain
      in laparoscopic total extra-peritoneal inguinal hernia repair: double-blinded
      randomized controlled trial. Kulasegaran S, Rohan M, Pearless L, Hulme-Moir M.

PMID- 29356908
TI  - Potential presence of metals in patients treated with metal-metal coupling
      prostheses for hip arthroplasty at 7 and 10 years of follow-up.
AB  - BACKGROUND: Beginning in 2008, metal-on-metal prostheses have been in the
      spotlight owing to much higher revision rates than expected. Adverse local tissue
      reactions have been well described in the literature as potential complications.
      METHODS: Between 2012 and 2013, 13 patients with metal-on-metal total hip
      replacements were evaluated clinically and radiologically and with laboratory
      samples. The same tests were repeated between 2015 and 2016 on eight patients to
      assess any changes. In the laboratory assessment, we searched for chromium,
      cobalt, molybdenum, and nickel in blood and urine samples over 24 h. RESULTS:
      Clinical assessment has shown good score in all patients except one. On a second
      examination, between 2015 and 2016, all patients obtained results similar to
      those obtained in the first assessment, except a patient, who reported a recent
      fall. In the radiological assessment between 2012 and 2013, results were optimal,
      apart from a case of aseptic mobilization. The patients reassessed 3 years after
      the first examination showed radiological results similar to those previously
      obtained, apart from a patient, who showed signals of mobilization. Metal levels
      found in their blood decreased in most cases after 3 years. Urine levels of
      nickel increased in five subjects, and chromium levels increased in four, but
      levels of cobalt and molybdenum decreased in four patients. CONCLUSION: It could
      be hypothesized that the decreasing trend of metal ion levels is associated with
      a stable wear status. On the contrary, a progressive increase in metal ion levels
      must be considered as early proof of implant loosening.

PMID- 29356911
TI  - Simple method to make a supersaturated oxygen fluid.
AB  - Intravenous oxygenation has demonstrated significant increase in partial pressure
      of oxygen (PO2) in animal models. A highly dissolved oxygen solution might be
      able to provide a sufficient level of oxygen delivery to the tissues and organs
      in patients with hypoxia. However, conventional fluid oxygenation methods have
      required the use of original devices. If simpler oxygenation of a solution is
      possible, it will be a useful strategy for application in clinical practice. We
      simply developed its administration by injection of either air or oxygen gas into
      conventional saline. We determined the PO2 values in the solutions in comparison
      with conventional saline in vitro. To examine the effects of the administration
      of the new solutions on the blood gas profile, we diluted bovine blood with
      either conventional or the new solutions and analyzed PO2, oxygen saturation
      (SO2) and total oxygen content. PO2 levels in the blood and new solution mixture
      significantly increased with each additional injected gas volume. Significant
      increases in the PO2 and SO2 of the bovine blood were found in those blood
      samples with the new solution, as compared with those with the control solution.
      These results suggest that this solution promotes oxygen delivery to the hypoxic
      tissue and recovery from hypoxia. This method is simpler and easier than previous
      methods.

PMID- 29356912
TI  - Current status and issues of the artificial pancreas: abridged English
      translation of a special issue in Japanese.
AB  - Surgical stress induces hyperglycemia and gives rise to glucose toxicity, which
      causes infectious diseases, resulting in unfavorable surgical outcomes. Intensive
      insulin treatment can control short- and long-term complications in patients with
      not only diabetes mellitus, but also surgical diabetes; however, it is associated
      with an increased risk of hypoglycemia. The wearable artificial pancreas was
      originally developed to control glucose levels in patients with type 1 diabetes,
      progressing to a device with enhanced stability and safety for these patients.
      Its usability has further progressed to include patients with type 2 diabetes.
      The bedside artificial pancreas is the only closed-loop-type artificial pancreas
      which can maintain stable glycemic control in accordance with a target blood
      glucose range, based on the patient's actual blood glucose levels. Moreover, this
      stable glycemic control with a low variation in blood glucose concentration
      within the target range is produced without any hypoglycemia. Significant
      advances of this device will now occur due to the approval of treatment for
      perioperative glycemic control by the Japanese Health Care Insurance System in
      2016. Along with an increase in the number of mainly elderly patients with low
      glucose tolerance, it is expected that the role of the artificial pancreas will
      increase in the future. Considering the current state and expense of regenerative
      and transplant medicine, along with donor shortages, further development of the
      artificial pancreas and associated glycemic control can be expected.

PMID- 29356913
TI  - Effect of a calcium chloride solution treatment on physical and mechanical
      properties of glass ionomer cements.
AB  - This paper details a novel method to improve wear resistance of dental glass
      ionomer cement (GIC) restorations. The purpose of this in vitro study was to
      evaluate the effect of a calcium chloride (CaCl2) solution treatment on surface
      hardness, surface roughness, compressive strength, water sorption and solubility
      of three conventional glass ionomer cements (GICs). Additionally, the changes of
      the Ca composition and morphology of the surface of the tested GICs were also
      investigated. The experimental groups of the study were: Group 1 (control)
      specimens after mixing were left in the mold to set without any treatment for 5
      min; Group 2 specimens were left in the mold to set for 5 min and then each
      specimen was immersed in 10 ml of 42.7 wt% CaCl2 solution for 60 s. Statistical
      analysis was performed using one-way ANOVA and Tukey post hoc tests (a = 0.05).
      Calcium chloride solution treatment increased surface hardness of the GICs
      compared to control groups (P < 0.05), while surface roughness and compressive
      strength did not change after the treatment (P > 0.05). Reduction in water
      sorption and solubility was detected but not in all CaCl2 solution-treatment
      groups. No alterations were observed in surface morphology of the GICs, while
      surface calcium composition was increased after the treatment (P < 0.05). The use
      of a CaCl2 solution immediately after initial setting of GICs may be advantageous
      for some properties of the materials and possibly leads to improved prognosis and
      wear resistance of their restorations.

PMID- 29356915
TI  - Single-Walled Carbon Nanotubes in Solar Cells.
AB  - Photovoltaics, more generally known as solar cells, are made from semiconducting
      materials that convert light into electricity. Solar cells have received much
      attention in recent years due to their promise as clean and efficient light
      harvesting devices. Single-walled carbon nanotubes (SWNTs) could play a crucial
      role in these devices and have been the subject of much research, which continues
      to this day. SWNTs are known to outperform multi-walled carbon nanotubes (MWNTs)
      at low densities, because of the difference in their optical transmittance for
      the same current density, which is the most important parameter in comparing
      SWNTs and MWNTs. SWNT films show semiconducting features, which make SWNTs
      function as active or charge-transporting materials. This chapter, consisting of
      two sections, focuses on the use of SWNTs in solar cells. In the first section,
      we discuss SWNTs as a light harvester and charge transporter in the photoactive
      layer, which are reviewed chronologically to show the history of the research
      progress. In the second section, we discuss SWNTs as a transparent conductive
      layer outside of the photoactive layer, which is relatively more actively
      researched. This section introduces SWNT applications in silicon solar cells,
      organic solar cells, and perovskite solar cells each, from their prototypes to
      recent results. As we go along, the science and prospects of the application of
      solar cells will be discussed.

PMID- 29356914
TI  - Clinical oral dryness score: evaluation of a new screening method for oral
      dryness.
AB  - The purpose of this study was to explore the association of the clinical oral
      dryness score (CODS) with salivary flow rates, xerostomia inventory (XI), and
      bother index (BI). 147 patients were screened using CODS, which determined 10
      features of oral dryness. Each feature contributed 1 point, and the total score
      varied from 0 to 10. Unstimulated (UWS), chewing-stimulated (CH-SWS) and acid
      stimulated (A-SWS) whole salivary flows and the XI and BI were measured.
      Associations were explored with a bootstrapped Spearman rank correlation test
      (1000 * bootstrapping). Based on unstimulated salivary flow, 55 patients were
      classified as hyposalivators, 31 as low salivators, 48 as normosalivators and 13
      as high salivators. Median CODS in the hyposalivation group was 5 (IQR 3-6)
      compared with 3 (IQR 2-5) in the low salivation group, 2 (IQR 1-4) in the normal
      salivation group and 2 (IQR 1-2.5) in the high salivation group. Significant
      associations between CODS and the other parameters were only found in the
      hyposalivation group between CODS and UWS (rho(53) = - 0.513; p < 0.01), between
      CODS and CH-SWS (rho(53) = - 0.453; p < 0.01), between CODS and A-SWS (rho(53) = 
      0.500; p < 0.01), CODS and XI (rho(53) = 0.343; p < 0.001) and between CODS and
      BI (rho(53) = 0.375; p = 0.01). In patients with hyposalivation, CODS is
      associated with unstimulated and stimulated salivary flow and XI and BI. CODS
      alone or a combination of CODS with a subjective measure, such as the XI or BI,
      could be recommended during routine clinical assessment to detect hyposalivation.

PMID- 29356916
TI  - Management and outcomes of women diagnosed with primary breast lymphoma: a multi
      institution experience.
AB  - PURPOSE: Primary breast lymphoma (PBL) comprises < 1% of breast malignancies,
      leading to a paucity of data to guide management. We evaluated PBL recurrence
      patterns across two academic hospitals in the era of modern systemic-therapy and
      radiotherapy. METHODS: Patients diagnosed with PBL between October 1994 and June
      2016 were identified. Demographic/clinical variables were assessed via primary
      chart review. Local control (LC) was estimated using the cumulative incidence
      function and overall survival (OS) using the Kaplan-Meier method. RESULTS: Thirty
      five patients were identified. Median follow-up 5.8 years (range 0.3-17.8 years).
      Median age at diagnosis 66 years (range 35-86 years). Indolent versus aggressive
      lymphoma represented 57% (n = 20) and 43% (n = 15) of the cohort, respectively.
      All patients with aggressive lymphoma received systemic therapy. Thirty patients
      (86%) received radiotherapy (RT). Breast-only RT was used in 57% (n = 20); 23% (n
      = 7) received regional nodal irradiation (RNI), and 6% (n = 2) received limited
      field RT. Local recurrences were observed in 3% (n = 1), contralateral breast 9%
      (n = 3), CNS 6% (n = 2), distant non-CNS 30% (n = 10), both local and distant 3%
      (n = 1). There were no regional nodal recurrences. The 6-year LC rate was 95% for
      indolent and 81% for aggressive subtypes. The 6-year OS rate was 87% for indolent
      and 70% for aggressive subtypes. CONCLUSIONS: The majority of patients in this
      PBL cohort received breast-only RT with no nodal relapses, suggesting that
      prophylactic RNI may be unnecessary. Given the prevalence of contralateral breast
      involvement at diagnosis and at recurrence, vigilant surveillance of bilateral
      breasts may be warranted. The role of CNS prophylaxis requires further
      investigation.

PMID- 29356917
TI  - Identification and analysis of CHEK2 germline mutations in Chinese BRCA1/2
      negative breast cancer patients.
AB  - PURPOSE: Cell-cycle-checkpoint kinase 2 (CHEK2) is an important moderate
      penetrance breast cancer predisposition gene; however, recurrent CHEK2 mutations
      found in Caucasian women are very rare in Chinese population. We investigated the
      mutation spectrum and clinical relevance of CHEK2 germline mutations in Chinese
      breast cancer patients. METHODS: The entire coding regions and splicing sites of
      CHEK2 were screened in 7657 Chinese BRCA1/2-negative breast cancer patients,
      using 62-gene panel-based sequencing. RESULTS: Out of 7657 BRCA1/2-negative
      breast cancer patients, 26 (0.34%) carried CHEK2 pathogenic germline mutations.
      Most of these mutations (92.3%, 24/26) were nonsense or frameshift mutations;
      84.6% (22/26) of them were in forkhead-associated (FHA) or kinase domains. Of the
      18 types of CHEK2 mutations we found, 61.1% (11/18) of were novel mutations and
      two recurrent mutations (Y139X and R137X) were found in this cohort. Patients
      with CHEK2 mutations were significantly more likely to have family histories of
      breast and/or ovarian cancer (23.1% vs. 8.6%, p = 0.022) and family histories of
      any cancer (50.0% vs. 31.6%, p = 0.044); and were significantly more likely to
      have lymph node-positive (53.8% vs. 27.3%, p = 0.002) and progesterone receptor
      (PR)-positive (88.5% vs. 64.5%, p = 0.011) breast cancers. CONCLUSIONS: Among
      Chinese breast cancer patients, the CHEK2 germline mutation rate is approximately
      0.34% and two specific mutations (Y139X and R137X) are recurrent. Patients with
      CHEK2 mutations are significantly more likely to have family histories of cancer,
      and to develop lymph node-positive and/or PR-positive breast cancers.

PMID- 29356918
TI  - Possible Breathing Influences on the Control of Arterial Pressure After Sino
      aortic Denervation in Rats.
AB  - PURPOSE OF REVIEW: Surgical removal of the baroreceptor afferents [sino-aortic
      denervation (SAD)] leads to a lack of inhibitory feedback to sympathetic outflow,
      which in turn is expected to result in a large increase in mean arterial pressure
      (MAP). However, few days after surgery, the sympathetic nerve activity (SNA) and
      MAP of SAD rats return to a range similar to that observed in control rats. In
      this review, we present experimental evidence suggesting that breathing
      contributes to control of SNA and MAP following SAD.The purpose of this review
      was to discuss studies exploring SNA and MAP regulation in SAD rats, highlighting
      the possible role of breathing in the neural mechanisms of this modulation of
      SNA. RECENT FINDINGS: Recent studies show that baroreceptor afferent stimulation
      or removal (SAD) results in changes in the respiratory pattern. Changes in the
      neural respiratory network and in the respiratory pattern must be considered
      among mechanisms involved in the modulation of the MAP after SAD.

PMID- 29356919
TI  - Influence of the oscillation frequency of different side-to-side toothbrushes on
      noncontact biofilm removal.
AB  - OBJECTIVES: The objective of this study was to investigate the influence of
      different oscillation frequencies of three powered toothbrushes with side-to-side
      action for noncontact biofilm removal in an artificial interdental space model.
      MATERIALS AND METHODS: A three-species biofilm (Porphyromonas gingivalis,
      Fusobacterium nucleatum and Streptococcus sanguinis) was formed in vitro on
      protein-coated titanium disks using a flow chamber system combined with a static
      biofilm growth model. The oscillation frequencies of three commercial side-to
      side toothbrushes were evaluated by means of a dose response. The frequency was
      decreased in steps (100, 85, 70, 55, and 40%). Subsequently, the biofilm-coated
      substrates were exposed to the side-to-side toothbrushes. The biofilm volumes
      were measured using volumetric analyses (Imaris 8.1.2) with confocal laser
      scanning microscope images (Zeiss LSM700). RESULTS: Compared to maximum
      oscillation frequency (100%), lower oscillation frequencies (up to 40%) resulted
      in reduced median percentages of biofilm reduction (median biofilm reduction up
      to 53% for maximum oscillation frequency, and up to 13% for 40% oscillation
      frequency) (p >= 0.03). In addition, decreasing the oscillation frequencies of
      the side-to-side toothbrushes showed an enhanced variety in the results of
      repeated experiments. CONCLUSIONS: The oscillation frequency of the tested side
      to-side toothbrushes affected the biofilm reduction in an interdental space
      model. CLINICAL RELEVANCE: Within a toothbrush, higher oscillation frequencies
      may lead to beneficial effects on interdental biofilm removal by noncontact
      brushing.

PMID- 29356921
TI  - Comparative study on the incision healing of the palatal mucosa by using Er:YAG
      laser or traditional scalpel in the SD rats.
AB  - The aim of this study was to compare the histology of wound healing following
      incisions with the scalpel or the Er:YAG laser in the palatal mucosa of SD rats.
      Two types of wounds were performed with the stainless steel scalpel or the Er:YAG
      laser in the palatal mucosa of SD rats, while the adjacent untreated palatal
      mucosa was chosen as control. Rats were sacrificed on day 1, day 3, day 7, and
      day 30 post-surgery. Biopsy samples from each wound were examined and the
      expression of IL-1beta and TGF-beta1 was determined by enzyme-linked
      immunosorbent assay (ELISA). The early postoperative incision of the scalpel
      group had obvious bleeding and swelling, while the laser wound mainly covered the
      surface of white pseudomembrane. The infiltration of neutrophils and lymphocytes
      in the stroma of the scalpel incision was more than that of the laser group.
      Compared to the laser group, 1 and 3 days after operation, the TGF-beta1 content
      of the scalpel group were significantly increased (P = 0.032 and 0.019). Seven
      days after operation, the TGF-beta1 content of two groups was decreased. TGF
      beta1 expression of control group was obviously increased (P > 0.05); 1, 3, and 7
      days after operation, the traditional scalpel amount of IL-1beta expression was
      significantly higher than that of control group (P = 0.000, 0.000, and 0.001).
      Postoperative day 1, IL-1beta expression of laser group and control group had no
      significant difference (P = 0.572). Three days after operation, IL-1beta
      expression of laser incision was increased and was significantly higher than that
      in control group (P = 0.032), however lower than the scalpel group (P = 0.03).
      Seven days after operation, the IL-1beta expression of two groups had no
      significant difference (P = 0.333); however, the IL-1beta expression of two
      groups were significantly higher than that of the control group (P = 0.02 and
      0.001). Compared to the traditional scalpel, the incision of Er:YAG laser has
      smaller inflammation reaction, more pseudomembrane coverage, and minimal damage
      of the mucoperiosteal tissue.

PMID- 29356920
TI  - 3D accuracy of implant positions in template-guided implant placement as a
      function of the remaining teeth and the surgical procedure: a retrospective
      study.
AB  - OBJECTIVE: The aim of this study was to investigate differences between the
      virtually planned and clinically achieved implant positions in completely
      template-guided implantations as a function of the type of edentulous space, the
      residual natural dentition, and the surgical implementation. MATERIALS AND
      METHODS: Fifty-six patient cases with a total of 122 implants were evaluated
      retrospectively. The implantations were completely template-based. The data of
      the planned implant positions were overlaid with the actual clinical implant
      positions, followed by measurements of the 3D deviations in terms of coronal (xc)
      and apical distance, height (xh), and angulation (ang) and statistical analysis.
      RESULTS: The mean xc was 1.2 mm (SD 0.7 mm); the mean xa was 1.8 mm (SD 0.9 mm),
      the mean xh was 0.8 mm (SD 0.7 mm); and the mean ang was 4.8 degrees  (SD 3.1).
      The type of edentulous space and the jaw (maxilla/mandible) had no significant
      effect on the results in terms of implant positions. The presence of an adjacent
      natural tooth at the time of implantation had a significant influence on xh (p =
      0.04) and ang (p = 0.05). No significant differences were found regarding the
      surgical approach for any of the parameters examined. CONCLUSION: The results of
      our study are in the same range as those of other studies. Template-guided
      implantation offers a high degree of accuracy even in the presence of different
      configurations of the residual dentition or different surgical approaches. A
      clinical benefit is therefore present, especially from a prosthetic point of
      view. CLINICAL RELEVANCE: The clinically achievable accuracy can be described as
      sufficient for further prosthetic treatment, given the intrinsic and
      methodological tolerances, making prosthetic rehabilitation safe and predictable.

PMID- 29356923
TI  - Expression pattern of YAP and TAZ during orthodontic tooth movement in rats.
AB  - Orthodontic tooth movement (OTM) is a periodontal tissue remodeling and
      regeneration process that is caused by bio-mechanical stimulation. This
      mechanical-chemical transduction process involves a variety of biological factors
      and signaling pathways. It has been shown that the Hippo-YAP/TAZ signaling
      pathway plays a pivotal role in the mechanical-chemical signal transduction
      process. Moreover, YAP and TAZ proteins interact with RUNX family proteins via
      different mechanisms. To explore the regulation of the Hippo signaling pathway
      during periodontal tissue remodeling, we examined the upper first molar OTM model
      in rats. We examined YAP, TAZ and RUNX2 expression at 12 hours, 24 hours, 2 days
      (2d), 4 days, 7 days (7d) and 14 days (14d) after force application. Haemotoxylin
      and eosin staining, immunohistochemical staining and western blot analysis were
      used to examine the expression level and localization of these proteins. We found
      that YAP, TAZ and RUNX2 expression started increasing at 2d, YAP and TAZ
      expression was proportional to the orthodontic force applied until peaking at 7d,
      and at 14d the expression started to decrease. YAP and TAZ were observed in
      osteocytes, bone matrix and periodontal ligament cells during OTM. Furthermore,
      using double labeling immunofluorescence staining, we found that the increase in
      TAZ expression was associated with RUNX2 expression, however, YAP and RUNX2
      showed different expression patterns. These results suggest that the Hippo
      YAP/TAZ signaling pathway participates in periodontal tissue remodeling through
      various mechanisms; TAZ may adjust bone tissue remodeling through RUNX2 during
      OTM, while YAP may regulate periodontal cell proliferation and differentiation.

PMID- 29356922
TI  - Point-by-point versus multisite electrode mapping in VT ablation: does freedom
      from VT recurrences depend on mapping catheter? An observational study.
AB  - PURPOSE: This study was conducted with the purpose of determining whether or not
      the potential technical advantages of multi-electrode mapping catheters in
      catheter ablation (CA) of ventricular tachycardia (VT) result in any relevant
      clinical benefit for VT patients. METHODS: A single-center VT study, having taken
      place from 2012 to 2014 using a standard 3.5-mm catheter (Thermocool SF(r) group
      1) and from 2014 to 2016 using a 1-mm multi-electrode-mapping catheter
      (PentaRay(r) group 2), was conducted. The endpoint was the complete elimination
      of late potentials (LPs), local abnormal ventricular activities (LAVA), and VT
      non-inducibility. Follow-up consisted of device interrogation to monitor for VT
      recurrence. RESULTS: Out of 74 VT patients aged 64.5 +/- 12.0 years (66 male
      [89.2%], 56 with ICM [75.7%], and 18 with NICM [24.3%)]), 48 patients (64.9%)
      were investigated in group 1 and 26 (35.1%) in group 2. Using the multi-point
      acquisition approach, a tendency to require less mapping time (group 1 65.2 +/-
      37.6 min, group 2 55.6 +/- 34.4 min, p ns) was determined. During 12-month follow
      up, 57 patients had freedom from VT recurrences (79.2%). The result was
      insignificant between the groups (38 patients (79.2%) in group 1 and 19 patients
      (73.1%) in group 2). CONCLUSIONS: In a single-center observational study, both
      conventional and high-density mapping approaches in VT patients are comparable in
      terms of procedure duration and outcome. Mapping time when using a multi
      electrode catheter seems to have the tendency of being shorter. We should be
      encouraged to recruit more patients comparing the benefit of different catheter
      types.

PMID- 29356924
TI  - Reflections on Six Decades of Research on Adolescent Behavior and Development.
AB  - These reflections, spanning six decades of involvement with developmental
      behavioral science, report on several salutarytrends that have shaped that field
      of social inquiry, e.g., its increasingly trans-disciplinary character. They also
      take note ofsome of its enduring limitations, e.g., its failure to engage with
      theory. In addition, the reflections confront some currentissues, such as the
      widespread stereotyping of adolescents as risk takers, and the growing recourse
      to reductionistexplanation. On balance, however, developmental behavioral science
      can be seen in retrospect as having evolved in adecidedly positive direction.
      Clearly, it has yielded a firmer grasp on adolescent behavior and development.

PMID- 29356925
TI  - Latent Class Analysis of Intimate Partner Violence Perpetration and Victimization
      among Latino Emerging Adults.
AB  - While there are known developmental consequences and correlates of intimate
      partner violence perpetration and victimization, research focused on
      bidirectional and multiple forms of partner violence among Latino emerging adults
      is needed. This longitudinal study identified latent classes of intimate partner
      violence perpetration and victimization patterns among emerging adult Latinos (N
      = 1060; 60.6% female). A second aim examined acculturation and cumulative
      substance use correlates in high school, as predictors of intimate partner
      violence perpetration and victimization classes in emerging adulthood. Average
      age of participants was 15.5 years in 10th grade and 22.7 years in emerging
      adulthood. We identified four distinct subgroups of intimate partner violence
      perpetration and victimization, with 22% of individuals identified in a violence
      perpetration and victimization subgroup. Cumulative heavy episodic drinking and
      marijuana use in high school predicted belonging to the psychological
      bidirectional intimate partner violence group rather than the group with no
      violence. Cumulative marijuana use in high school, predicted belonging to the
      sexual bidirectional partner violence group compared to the no violence group.
      Our study extends the literature across developmental periods among Latino youth.
      The findings have implications for early adolescent prevention strategies and
      promotion of healthy intimate relationships.

PMID- 29356926
TI  - Examining Relationships among Choice, Affect, and Engagement in Summer STEM
      Programs.
AB  - Out-of-school time programs focused on science, technology, engineering and
      mathematics (STEM) have proliferated recently because they are seen as having
      potential to appeal to youth and enhance STEM interest. Although such programs
      are not mandatory, youth are not always involved in making the choice about their
      participation and it is unclear whether youth's involvement in the choice to
      attend impacts their program experiences. Using data collected from experience
      sampling, traditional surveys, and video recordings, we explore relationships
      among youth's choice to attend out-of-school time programs (measured through a
      pre-survey) and their experience of affect (i.e., youth experience sampling
      ratings of happiness and excitement) and engagement (i.e., youth experience
      sampling ratings of concentration and effort) during program activities. Data
      were collected from a racially and ethnically diverse sample of 10-16 year old
      youth (n = 203; 50% female) enrolled in nine different summer STEM programs
      targeting underserved youth. Multilevel analysis indicated that choice and affect
      are independently and positively associated with momentary engagement. Though
      choice to enroll was a significant predictor of momentary engagement, positive
      affective experiences during the program may compensate for any decrements to
      engagement associated with lack of choice. Together, these findings have
      implications for researchers, parents, and educators and administrators of out-of
      school time programming.

PMID- 29356927
TI  - Image-guided resection of glioblastoma in eloquent brain areas facilitated by
      laser surface thermal therapy: clinical outcomes and long-term results.
AB  - The increased interest in the application of lasers in neuro-oncology prompted us
      to present our experience of using the laser technologies in the treatment of
      cerebral gliomas. The aim of the study was to evaluate the clinical efficacy of
      image-guided laser surface thermal therapy (LSTT) and its influence on survival
      of patients with glioblastoma (GBM).Data of 91 patients (49 males, 42 females,
      mean age 51.4 years, range 23-70 years) with supratentorial GBMs located in close
      vicinity to or within the eloquent brain areas were retrospectively analyzed.All
      patients were divided into two groups: LSTT group (n = 28) and control group (n =
      63). There were no significant differences by gender, age, Karnofsky Performance
      Scale (KPS) score, and tumor location between groups. Total removal in the LSTT
      group was performed in 67.9%, in the control group-31.7% (p < 0.01); on the
      contrary, subtotal removal prevailed in the control group-52.4%; in the LSTT
      group, it was 32.1%. In postoperative period, there was no significant difference
      in KPS score between the groups (p = 0.89). A higher degree of resection provided
      an increase in survival rates (p < 0.01). The median overall survival was 15.5 +/
      10.5 months, in the LSTT group 18.4 +/- 11.7 and in the control group 14.3 +/-
      9.1 (p = 0.03). The application of image-guided LSTT in patients with GBMs of
      eloquent brain areas allowed the high rate of complete resection and improved
      overall survival without the negative effect on the functional status after
      surgery.

PMID- 29356928
TI  - The Closing Digital Divide: Delivery Modality and Family Attendance in the
      Pathways for African American Success (PAAS) Program.
AB  - Although family-focused, evidence-based programs (EBPs) have the potential to
      reduce disparities in health and behavioral outcomes for youth, access to such
      programs is severely limited in the most affected areas, including African
      American communities in the rural South. As expanding the reach of EBPs is the
      primary goal of translational research, interest is growing in the potential of
      technology as a viable platform to disseminate services to areas with limited
      resources. To test whether African American families in the rural South would be
      willing to engage in a technology-based family-focused EBP to prevent adolescent
      risk behavior, we examined attendance using data from two arms of a three-arm
      community-based trial of the Pathways for African American Success (PAAS)
      program. In the overall study, sixth graders (N = 412) and their primary
      caregivers were randomly assigned to the following conditions: (a) in-person,
      small group sessions led by facilitators; (b) self-directed, technology-based
      sessions; or (c) a literature control with home-mailed educational materials.
      Results indicated that attendance was higher in the technology condition than in
      the small group condition. Parental age, education, and socioeconomic status did
      not limit attendance in the technology condition. We conclude from these results
      that the use of technology can be an acceptable strategy for disseminating
      parenting EBPs to African American families in the rural South.

PMID- 29356929
TI  - Dealing with the Conflicting Results of Psycholinguistic Experiments: How to
      Resolve Them with the Help of Statistical Meta-analysis.
AB  - This paper proposes the use of the tools of statistical meta-analysis as a method
      of conflict resolution with respect to experiments in cognitive linguistics. With
      the help of statistical meta-analysis, the effect size of similar experiments can
      be compared, a well-founded and robust synthesis of the experimental data can be
      achieved, and possible causes of any divergence(s) in the outcomes can be
      revealed. This application of statistical meta-analysis offers a novel method of
      how diverging evidence can be dealt with. The workability of this idea is
      exemplified by a case study dealing with a series of experiments conducted as non
      exact replications of Thibodeau and Boroditsky (PLoS ONE 6(2):e16782, 2011.
      https://doi.org/10.1371/journal.pone.0016782 ).

PMID- 29356930
TI  - Correction to: Heat stress alters genome-wide profiles of circular RNAs in
      Arabidopsis.
AB  - Due to an unfortunate turn of events, the first name of the fifth author appeared
      incorrectly in the original publication and should have read Guangbing. The
      correct representation of the authors' names and their affiliation is listed here
      and should be treated as definitive.

PMID- 29356932
TI  - Impact of a new cryotherapy device on early rehabilitation after primary total
      knee arthroplasty (TKA): a prospective randomised controlled trial.
AB  - BACKGROUND: The aim of this prospective, randomised and single blinded study was
      to evaluate the efficiency and safety of a new cryotherapy device in patients
      undergoing unilateral, primary total knee arthroplasty (TKA). Our hypothesis was
      that patients administered to the new cryotherapy device would perform better
      than patients receiving a conventional standard cold therapy regimen. METHODS:
      Ninety-seven patients were randomised into two groups receiving either the
      cTreatment(r) (new cryotherapy device) or the standard cold therapy protocol
      (including cold pack application for six days after the surgical intervention).
      We evaluated the following endpoints consisting of range of motion (ROM), pain
      intensity, and knee girth on admission day and the second, fourth, and sixth post
      operative day (POD). RESULTS: A statistically significant benefit of the new
      cryotherapy device was detected regarding the ROM on the sixth POD with an
      average gain of 7 degrees (p = 0.021). Pain in the numeric rating scale (NRS)
      score in motion was significantly lower in the cTreatment(r) group on the second
      POD (p = 0.034). There were no statistically significant differences between
      groups regarding the NRS in rest, patient controlled analgesia (PCA) consumption,
      and girth measurements. No adverse effects were observed in both study groups.
      CONCLUSION: The new computer-controlled cooling therapy device provides benefits
      in terms of early post-operative remobilisation with respect to ROM and pain,
      which might be attributed to a reduced inflammatory response, as well as reduced
      secretion and bleeding. The cTreatment(r) system appears to be a safe and
      efficient procedure.

PMID- 29356931
TI  - CX3CL1/CX3CR1 Axis Contributes to Angiotensin II-Induced Vascular Smooth Muscle
      Cell Proliferation and Inflammatory Cytokine Production.
AB  - Angiotensin II (Ang II) dysregulation has been determined in many diseases. The
      CX3CL1/CX3CR1 axis, which has a key role in cardiovascular diseases, is involved
      in the proliferation and inflammatory cytokine production of vascular smooth
      muscle cells (VSMCs). In this study, we aim to explore whether Ang II has a role
      in the expression of CX3CL1/CX3CR1, thus contributing to the proliferation and
      pro-inflammatory status of VSMCs. Cultured mouse aortic VSMCs were stimulated
      with 100 nmol/L of Ang II, and the expression of CX3CR1 was assessed by western
      blot. The results demonstrated that Ang II significantly up-regulated CX3CR1
      expression in VSMCs and induced the production of reactive oxygen species (ROS)
      and the phosphorylation of p38 MAPK. Inhibitors of NADPH oxidase, ROS, and AT1
      receptor significantly reduced Ang II-induced CX3CR1 expression. Targeted
      disruption of CX3CR1 by transfection with siRNA significantly attenuated Ang II
      induced VSMC proliferation as well as down-regulated the expression of
      proliferating cell nuclear antigen (PCNA). Furthermore, CX3CR1-siRNA suppressed
      the effect of Ang II on stimulating Akt phosphorylation. Besides, the use of
      CX3CR1-siRNA decreased inflammatory cytokine production induced by Ang II
      treatment. Our results indicate that Ang II up-regulates CX3CR1 expression in
      VSMCs via NADPH oxidase/ROS/p38 MAPK pathway and that CX3CL1/CX3CR1 axis
      contributes to the proliferative and pro-inflammatory effects of Ang II in VSMCs.

PMID- 29356933
TI  - How to accurately determine the distal femoral valgus cut angle in the valgus
      knee arthroplasty.
AB  - PURPOSE: Distal femoral resection in total knee arthroplasty (TKA) is commonly
      performed using intramedullary jigs with a pre-operatively planned valgus cut
      angle (VCA). For valgus knees with lateral femoral condyle hypoplasia, the method
      of determining the accurate VCA has not been clarified. The aim of the present
      study is to introduce a method that can accurately determine the distal femoral
      VCA in the valgus knee arthroplasty. METHODS: Twenty patients with valgus
      deformity caused by lateral femoral condylar hypoplasia underwent primary TKA
      with individually measured VCA. The VCA was defined as the acute crossing angle
      of the anatomical and mechanical axes of the femur on a pre-operative X-ray film,
      and the two axes almost always crossed at the distal femoral diaphysis, but not
      the centre of the knee as generally described. The entry point of the femoral
      intramedullary guide rod was determined on the extension of the femoral
      anatomical axis and was usually medial to the centre of the knee. According to
      the pre- and post-operative X-ray films, the mechanical lateral distal femoral
      angle (mLDFA), and coronal alignment of the femoral components were measured. The
      post-operative knee pain and function were evaluated using the Visual Analog
      Scale and Knee Society Score, respectively. RESULTS: The mean VCA measured
      according to the above method was 6.4 degrees  +/- 1.0 degrees  (4.7-8.2 degrees
      ), and the femoral entry point was located at a mean distance of 7.4 +/- 2.1 mm
      (4.5-10.9 mm) medial to the centre of the knee joint. The mean mLDFA before and
      after operation was 77.4 degrees  +/- 5.7 degrees  (74-82 degrees ) and 88.4
      degrees  +/- 1.7 degrees  (86-90 degrees ), respectively, showing a statistically
      significant difference (P < 0.01). CONCLUSIONS: The deformity of the distal
      femoral diaphysis is quite various in different valgus knees. The VCA and the
      femoral entry point should be determined individually for each case. The
      application of the current method resulted in good post-operative mechanical axis
      alignment and clinical results after TKA. LEVEL OF EVIDENCE: Level IV.

PMID- 29356934
TI  - Elevated levels of serum sclerostin are linked to adverse cardiovascular outcomes
      in peritoneal dialysis patients.
AB  - PURPOSE: To investigate the correlation between elevated serum sclerostin levels
      and chronic kidney disease outcomes for patients receiving peritoneal dialysis
      (PD). METHODS: We performed a prospective observational study in stable PD
      patients. Serum sclerostin levels were determined via enzyme immunoassay, and
      median levels of sclerostin were used to divide patients into high and low
      sclerostin groups. New-onset cardiovascular events (CVEs) and cardiovascular
      mortality were evaluated during a 6-year follow-up period. RESULTS: Ninety-eight
      patients [mean age 52.5 +/- 10.9 years, 49% males, 21.4% diabetic, median
      dialysis vintage 40.7 (range 17.9-72.2) months] were recruited. Compared with
      those in the low sclerostin group, patients in the high sclerostin group
      demonstrated higher levels of total-cholesterol, NT-proBNP, and osteoprotegerin
      (all P < 0.05). During the 6-year study period, 25 CVEs and 17 cardiovascular
      deaths occurred in the high sclerostin group, whereas 11 CVEs and four
      cardiovascular deaths occurred in the low sclerostin group. A Cox regression
      analysis determined that high sclerostin levels significantly increased the risk
      for CVEs (HR 2.475, 95% CI 1.116-5.489, P = 0.026) and cardiovascular death (HR
      3.484, 95% CI1.134-10.706, P = 0.029), after multiple adjustments were made.
      CONCLUSIONS: Our data suggest that high sclerostin levels may predict the onset
      of CVEs and cardiovascular mortality among PD patients.

PMID- 29356935
TI  - Patterning of individual heterogeneity in body mass index: evidence from 57 low-
      and middle-income countries.
AB  - Modeling variation at population level has become increasingly valued, but no
      clear application exists for modeling differential variation in health between
      individuals within a given population. We applied Goldstein's method (in:
      Everrit, Howell (eds) Encyclopedia of statistics in behavioral science, Wiley,
      Hoboken, 2005) to model individual heterogeneity in body mass index (BMI) as a
      function of basic sociodemographic characteristics, each independently and
      jointly. Our analytic sample consisted of 643,315 non-pregnant women aged 15-49
      years pooled from the latest Demographic Health Surveys (rounds V, VI, or VII;
      years 2005-2014) across 57 low- and middle-income countries. Individual
      variability in BMI ranged from 9.8 (95% CI: 9.8, 9.9) for the youngest to 23.2
      (95% CI: 22.9, 23.5) for the oldest age group; 14.2 (95% CI: 14.1, 14.3) for
      those with no formal education to 19.7 (95% CI: 19.5, 19.9) for those who have
      completed higher education; and 13.6 (95% CI: 13.5, 13.7) for the poorest
      quintile to 20.1 (95% CI: 20.0, 20.2) for the wealthiest quintile group.
      Moreover, variability in BMI by age was also different for different
      socioeconomic groups. Empirically testing the fundamental assumption of constant
      variance and identifying groups with systematically large differentials in health
      experiences have important implications for reducing health disparity.

PMID- 29356936
TI  - Does Aeroallergen Sensitization Cause or Contribute to Eosinophilic Esophagitis?
AB  - Eosinophilic esophagitis is an atopic disease defined clinically by esophageal
      symptoms in combination with a dense esophageal eosinophilia. EoE is triggered
      and maintained by exposure to certain foods and it is known that dietary
      modification controls symptoms and achieves disease remission. Recently,
      aeroallergens have been implicated in the pathogenesis of EoE. To examine the
      role of aeroallergens in EoE, we reviewed the published literature. Sensitization
      and production of IgE antibodies to foods and aeroallergens in subjects with EoE
      has been demonstrated. However, the evidence suggests only a minor role for IgE
      mediated immune reactions in EoE. There is some evidence to support an
      association of EoE diagnosis and flares with environmental allergen exposure, and
      animal studies support the notion that EoE may be induced by exposure to inhalant
      allergens. Some studies show that newly diagnosed cases of EoE follow a seasonal
      pollen distribution (summer and spring), but the weight of evidence does not
      support the seasonal occurrence of diagnosis or worsening of symptoms. Overall,
      we conclude that the current evidence does not support causality in inhalant
      allergen exposure and the genesis nor exacerbations of EoE in humans, although
      there is a possibility that inhalant allergen sensitization could play a
      modifying role in EoE in the context of cross-reacting food allergens.

PMID- 29356937
TI  - A Retrospective Assessment of Four Antigen Assays for the Detection of Invasive
      Candidiasis Among High-Risk Hospitalized Patients.
AB  - Because of their high mortality rates and non-specific symptoms, invasive Candida
      infections pose a huge diagnostic and therapeutic challenge. In this study, we
      evaluated the three mannan antigen assays Platelia, Platelia Plus and Serion, and
      the (1-3)-beta-D-glucan assay Fungitell in a group of high-risk (hematological
      and surgical) patients. Test results of 305 patients hospitalized at the Vienna
      General Hospital and the University Hospital of Innsbruck were retrospectively
      analyzed. We assessed the test accuracy by means of descriptive statistics. Nine
      (2.95%) patients were affected by invasive candidiasis (IC), and 25 (8.2%)
      patients had a probable/possible infection. The majority of patients (271; 88.9%)
      showed no signs of infection. The Platelia and Serion mannan assays had a low
      sensitivity (65% and 52%, respectively), but high specificity (98% for both
      tests). The newer version of the Platelia assay, the Platelia Plus, had a higher
      sensitivity (85%) but a lower specificity (89%). The sensitivity of the Fungitell
      assay was high (100%), while its specificity was low (58%). The positive
      predictive values were 0.48 for the Platelia and 0.41 for the Serion assay, 0.26
      for the Platelia Plus and 0.09 for the Fungitell assay. Our limited,
      retrospective study suggests the efficacy of mannan assays as screening (Platelia
      Plus) and confirmatory (Serion) tests, while the Fungitell assay can be used to
      exclude invasive Candida infections.

PMID- 29356938
TI  - Reconstructing the demographic history of the Himalayan and adjoining
      populations.
AB  - The rugged topography of the Himalayan region has hindered large-scale human
      migrations, population admixture and assimilation. Such complexity in
      geographical structure might have facilitated the existence of several small
      isolated communities in this region. We have genotyped about 850,000 autosomal
      markers among 35 individuals belonging to the four major populations inhabiting
      the Himalaya and adjoining regions. In addition, we have genotyped 794
      individuals belonging to 16 ethnic groups from the same region, for uniparental
      (mitochondrial and Y chromosomal DNA) markers. Our results in the light of
      various statistical analyses suggest a closer link of the Himalayan and adjoining
      populations to East Asia than their immediate geographical neighbours in South
      Asia. Allele frequency-based analyses likely support the existence of a specific
      ancestry component in the Himalayan and adjoining populations. The admixture time
      estimate suggests a recent westward migration of populations living to the East
      of the Himalaya. Furthermore, the uniparental marker analysis among the Himalayan
      and adjoining populations reveal the presence of East, Southeast and South Asian
      genetic signatures. Interestingly, we observed an antagonistic association of Y
      chromosomal haplogroups O3 and D clines with the longitudinal distance. Thus, we
      summarise that studying the Himalayan and adjoining populations is essential for
      a comprehensive reconstruction of the human evolutionary and ethnolinguistic
      history of eastern Eurasia.

PMID- 29356939
TI  - Identification of rare RTN3 variants in Alzheimer's disease in Han Chinese.
AB  - Reticulon 3 (RTN3) is a neuronally-expressed reticulon family protein that was
      previously shown to negatively regulate BACE1, a protease that is required for
      the generation of beta-amyloid peptides (Abeta) from amyloid precursor protein.
      Despite biochemical and morphological evidence that supports a role of RTN3 in
      the formation of neuritic amyloid plaques, no systematic analyses of RTN3
      mutations in patients with Alzheimer's disease (AD) have yet been reported. RTN3
      were targeted sequenced in 154 sporadic early-onset and 285 late-onset AD
      patients. Luciferase reporter assay and kymographs were performed to analysis the
      expression of RNT3 and BACE1-RFP particle mobility on cells transfected with wild
      type or variants RTN3 constructs. We identified heterozygous variants such as c.
      8G > T, c.17C > A, c.42C > T, and c.116C > T from patients in the early-onset AD
      group and c.-8G > T, c.17C > A, from patients in the late-onset AD group. Such
      variants of RTN3 were not observed in control individuals. Further biochemical
      studies show that the RTN3 c.-8G > T variant in the 5'-untranslated region
      appears to cause reduced expression of RTN3. The RTN3 c.116 C > T variant causes
      a change of codon T39 to M39 (T39 M). Overexpression of RTN3 T39 M in cultured
      neurons led to impaired axonal transport of BACE1. The variants found in this
      study are likely genetic modifiers for RTN3-mediated formation of neuritic
      plaques in AD.

PMID- 29356940
TI  - The effect of humeral-fenestration diameter in Outerbridge-Kashiwagi arthroplasty
      on failure load of the distal humerus: a cadaveric biomechanical study.
AB  - INTRODUCTION: Outerbridge-Kashiwagi ulnohumeral arthroplasty is an effective
      method in treating elbow osteoarthritis; however, distal humerus fracture after
      surgery can become a critical issue. A previous biomechanical study has shown
      that the failure load of the distal humerus decreases after a fenestration, but
      the size of the fenestration hole has not yet been discussed. MATERIALS AND
      METHODS: 32 fresh-frozen cadaveric distal humeri were obtained. Two drill sizes
      were chosen for fenestration: 12 and 15 mm in diameter. Two directions of force
      were applied with a materials testing machine for biomechanical testing: 5
      degrees  flexion for axial loading and 75 degrees  flexion for anterior-posterior
      (AP) loading. Each specimen randomly received one of the two fenestration sizes,
      and force directions. All specimens were loaded to failure at a rate of 2 mm/min.
      RESULTS: The failure loads of the 12 and 15 mm groups were not significantly
      different in either axial loading(3886 +/- 1271 N vs 4286 +/- 901 N) or AP
      loading(2303 +/- 803 N vs 1897 +/- 357 N). All specimens loaded with axial force
      failed via the fenestration holes; however, during AP loading, some specimens
      failed through the fenestration holes, while others at diaphysis (p = 0.28).
      CONCLUSIONS: The failure load of distal humeri did not differ significantly after
      fenestration of 12 or 15 mm. The clinical relevance is that as the risk of distal
      humerus fracture is not exacerbated, a larger-size fenestration hole could be of
      help to improve the effectiveness of this surgical procedure.

PMID- 29356941
TI  - Femoral component alignment in unicompartmental knee arthroplasty leads to
      biomechanical change in contact stress and collateral ligament force in knee
      joint.
AB  - BACKGROUND: In recent years, the popularity of unicompartmental knee arthroplasty
      (UKA) has increased. However, the effect of femoral component positioning in UKA
      continues to invite a considerable debate. The purpose of this study involved
      assessing the biomechanical effect of mal-alignment in femoral components in UKA
      under dynamic loading conditions using a computational simulation. METHODS: A
      validated finite element model was used to evaluate contact stresses in
      polyethylene (PE) inserts and lateral compartment and force on collateral
      ligament in the femoral component ranging from 9 degrees  of varus to 9 degrees 
      of valgus. RESULTS: The results indicated that contact stress on the PE insert
      increased with increases in the valgus femoral alignment when compared to the
      neutral position while contact stress on the lateral compartment increased with
      increases in the varus femoral alignment. The forces on medial and lateral
      collateral ligaments increased with increases in valgus femoral alignments when
      compared to the neutral position. However, there was no change in popliteofibular
      and anterior lateral ligaments with respect to the malpositioning of femoral
      component. CONCLUSION: The results of the study confirm the importance of
      conservation in post-operative accuracy of the femoral component since the valgus
      and varus femoral malalignments affect the collateral ligament and lateral
      compartment, respectively. Our results suggest that surgeons should avoid valgus
      malalignment in the femoral component and especially malalignment exceeding 9
      degrees , which may induce higher medial collateral ligament forces.

PMID- 29356942
TI  - Mid-term outcome of arthroscopic AMIC for the treatment of articular cartilage
      defects in the knee joint is equivalent to mini-open procedures.
AB  - INTRODUCTION: We present the first retrospective study that compares two various
      autologous matrix-induced chondrogenesis (AMIC) surgical interventions to repair
      grade III-IV cartilage defects in the knee. Patients who underwent minimally
      invasive (arthroscopy) or open (mini-arthrotomy) AMIC were followed up to 2 years
      to investigate if minimally invasive AMIC is superior to open procedures.
      MATERIALS AND METHODS: Overall n = 50 patients with focal and contained grade III
      IV articular cartilage defects in the knee joint were followed in a consecutive
      cohort study. 20 patients were treated arthroscopically (female 7, male 13; age:
      mean 38.2 years, range 18-70 years; BMI: mean 27.0, range 18.7-34.7; defect size:
      mean 3.1 cm2, range 1.0-6.0 cm2), and 30 patients via mini-arthrotomy (female 13,
      male 17; age: mean 34.4 years, range 14-53 years, BMI: mean 23.9, range 18.4
      28.7; defect size: mean 3.4 cm2, range 1.5-12.0 cm2). The primary defect
      localization was the medial femoral condyle. RESULTS: AMIC led to a significant
      improvement of VAS pain, KOOS and Lysholm scoring for up to 2 years compared to
      pre-op. Outcome analysis revealed no significant differences between the two
      different surgical approaches. CONCLUSIONS: Our results suggest that mini-open
      AMIC is equivalent to the arthroscopic procedure. The anticipatory hypothesis
      that minimally invasive approaches bring greater patient benefit per se could not
      be confirmed. Therefore, we recommend to perform AMIC where indicated and suggest
      that the surgeon's personal skills profile guide the choice of surgical approach.
      LEVEL OF EVIDENCE: III.

PMID- 29356943
TI  - Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration.
AB  - A previous study has indicated that Kruppel-like factor 7 (KLF7), a transcription
      factor that stimulates Schwann cell (SC) proliferation and axonal regeneration
      after peripheral nerve injury, is a promising therapeutic transcription factor in
      nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b)
      affected SC proliferation, migration, and myelinated axon regeneration following
      sciatic nerve injury by regulating its direct target KLF7. SCs were transfected
      with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in
      vitro. The expression of miR146b and KLF7, as well as SC proliferation and
      migration, were subsequently evaluated. In vivo, an acellular nerve allograft
      (ANA) followed by injection of GFP control vector or a lentiviral vector encoding
      an miR-146b inhibitor was used to assess the repair potential in a model of
      sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR,
      suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly
      reduced the proliferation and migration of SCs, whereas silencing miR-146b
      resulted in increased proliferation and migration. KLF7 protein was localized in
      SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA,
      anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade,
      promoting axonal outgrowth. Closer analysis revealed improved nerve conduction
      and sciatic function index score, and enhanced expression of neurofilaments, P0
      (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide
      new insight into the regulation of KLF7 by miR-146b during peripheral nerve
      regeneration and suggest a potential therapeutic strategy for peripheral nerve
      injury.

PMID- 29356944
TI  - A case of lipoprotein glomerulopathy with a rare apolipoprotein E isoform
      combined with neurofibromatosis type I.
AB  - Lipoprotein glomerulopathy (LPG) is a rare inherited disease characterized by
      histopathological features of lipoprotein thrombi in dilated glomerular
      capillaries and type III like hyperlipoproteinemia with heterozygous mutation of
      the apolipoprotein (apo) E gene. We herein present the case of a 50-year-old
      woman with LPG complicated by neurofibromatosis type 1 (NF1). To the best of our
      knowledge, this is the first report of a case of LPG complicated by NF1. On the
      other hand, she had not only a heterozygous apoE-Sendai mutation, which is one of
      the most frequent apoE variants in LPG patients, but also a rare isoform of ApoE5
      (Glu3Lys). Although apoE mutation has been recognized as having a principal role
      in the pathogenesis of LPG, some other factors are assumed to be present in the
      pathogenesis of LPG, because many asymptomatic carriers of apoE variants are
      recognized. The coexistence of NF1 or apoE5 (Glu3Lys) allele might play a role as
      an additional factor in the development of LPG.

PMID- 29356945
TI  - Mechanical birth-related trauma to the neonate: An imaging perspective.
AB  - Mechanical birth-related injuries to the neonate are declining in incidence with
      advances in prenatal diagnosis and care. These injuries, however, continue to
      represent an important source of morbidity and mortality in the affected patient
      population. In the United States, these injuries are estimated to occur among
      2.6% of births. Although more usual in context of existing feto-maternal risk
      factors, their occurrence can be unpredictable. While often superficial and
      temporary, functional and cosmetic sequelae, disability or even death can result
      as a consequence of birth-related injuries. The Agency for Healthcare research
      and quality (AHRQ) in the USA has developed, through expert consensus, patient
      safety indicators which include seven types of birth-related injuries including
      subdural and intracerebral hemorrhage, epicranial subaponeurotic hemorrhage,
      skeletal injuries, injuries to spine and spinal cord, peripheral and cranial
      nerve injuries and other types of specified and non-specified birth trauma.
      Understandably, birth-related injuries are a source of great concern for the
      parents and clinician. Many of these injuries have imaging manifestations. This
      article seeks to familiarize the reader with the clinical spectrum, significance
      and multimodality imaging appearances of neonatal multi-organ birth-related
      trauma and its sequelae, where applicable. Teaching points * Mechanical trauma
      related to birth usually occurs with pre-existing feto-maternal risk factors.*
      Several organ systems can be affected; neurologic, musculoskeletal or visceral
      injuries can occur.* Injuries can be mild and transient or disabling, even life
      threatening.* Imaging plays an important role in injury identification and triage
      of affected neonates.

PMID- 29356946
TI  - Genetic characterization of Rio de Janeiro for different Y-STR sets.
AB  - In this work, the YfilerPlus kit was used to investigate a sample of 258 males
      from Rio de Janeiro. In addition, the previous database of 760 Yfiler profiles
      deposited in the YHRD was updated to 1610. YfilerPlus markers showed a high
      haplotype diversity (0.99997), with only one haplotype shared by two individuals.
      When only considering the Yfiler markers, the haplotype diversity was slightly
      lower (0.99976), with 5 haplotypes shared by two individuals and 1 haplotype
      shared by three individuals. Low genetic distances were found between the Rio de
      Janeiro and European populations as well as the European/Hispanic American
      samples.

PMID- 29356947
TI  - Forensic application of epidermal AQP3 expression to determination of wound
      vitality in human compressed neck skin.
AB  - In forensic practices, it is often difficult to determine wound vitality in
      compression marks of the neck with naked eyes. AQP1 and AQP3 are the major water
      channels associated with skin. Thus, we immunohistochemically examined the
      expression of AQP1 and AQP3 in neck skin samples to discuss their forensic
      applicability to determination of the wound vitality. Skin samples were obtained
      from 56 neck compression cases (hanging, 35 cases; strangulation, 21 cases). The
      intact skin from the same individual was taken as a control. Although AQP1 was
      immnunostained in dermal capillaries in both the neck compression marks and
      intact skin samples, there was no significant difference in the magnitude of AQP1
      expression between both groups. On the contrary, AQP3-positive signals could be
      faintly detected in uninjured skin samples, and the positive signals seemed more
      intense in the keratinocytes in compression regions. Morphometrical analyses
      revealed that the ratio of AQP3-expressed keratinocytes was significantly
      enhanced in neck compression regions, compared with control groups. From the
      viewpoints of forensic pathology, immunohistochemical detection of AQP3 in the
      neck skin can be considered a valuable marker to diagnose the trace of antemortem
      compression.

PMID- 29356948
TI  - Effect of dietary nitrate supplementation on thermoregulatory and cardiovascular
      responses to submaximal cycling in the heat.
AB  - PURPOSE: This study investigated whether reported improvements in blood flow
      distribution, and the possible related effects on thermoregulation during
      exercise following supplementation with beetroot juice (BR), a rich source of
      dietary nitrate (NO3-), are mitigated in the heat. METHODS: 12 male endurance
      trained cyclists (age 27 +/- 6 years, VO2peak 68.6 +/- 8.1 ml kg-1 min-1)
      completed two 60 min submaximal cycling trials at 60% of VO2peak power output.
      Trials were performed in hot environmental conditions (33.3 +/- 0.4  degrees C,
      48.8 +/- 3.0% RH) following 3 days of supplementation with either NO3--rich BR
      (6.5 mmol NO3- for 2 days and 13 mmol NO3- on the final day) or NO3--depleted
      placebo (PLA). Salivary NO3- and nitrite (NO2-) were measured before and after
      the supplementation period. During exercise, cutaneous blood flow, blood pressure
      (MAP), core temperature (Tc), mean skin temperature (Tsk), indices of muscle
      oxygenation and oxygen (O2) consumption were measured. RESULTS: Salivary NO3- and
      NO2- increased significantly following BR by 680 and 890%, respectively. There
      were no significant differences observed for cutaneous blood flow, MAP, Tc, Tsk,
      muscle oxygenation, or O2 consumption between BR and PLA. CONCLUSION: This
      investigation shows that the ergogenic effects and health benefits of BR
      supplementation, such as augmented cutaneous blood flow, reduced MAP, increased
      muscle oxygenation, and improved aerobic efficiency may be attenuated when
      exercise is performed in hot conditions.

PMID- 29356949
TI  - Validity of the Polar V800 monitor for measuring heart rate variability in
      mountain running route conditions.
AB  - PURPOSE: This study was conducted to test, in mountain running route conditions,
      the accuracy of the Polar V800TM monitor as a suitable device for monitoring the
      heart rate variability (HRV) of runners. METHOD: Eighteen healthy subjects ran a
      route that included a range of running slopes such as those encountered in trail
      and ultra-trail races. The comparative study of a V800 and a Holter SEER 12 ECG
      RecorderTM included the analysis of RR time series and short-term HRV analysis. A
      correction algorithm was designed to obtain the corrected Polar RR intervals. Six
      5-min segments related to different running slopes were considered for each
      subject. RESULTS: The correlation between corrected V800 RR intervals and Holter
      RR intervals was very high (r = 0.99, p < 0.001), and the bias was less than 1
      ms. The limits of agreement (LoA) obtained for SDNN and RMSSD were (- 0.25 to
      0.32 ms) and (- 0.90 to 1.08 ms), respectively. The effect size (ES) obtained in
      the time domain HRV parameters was considered small (ES < 0.2). Frequency domain
      HRV parameters did not differ (p > 0.05) and were well correlated (r >= 0.96, p <
      0.001). CONCLUSION: Narrow limits of agreement, high correlations and small
      effect size suggest that the Polar V800 is a valid tool for the analysis of heart
      rate variability in athletes while running high endurance events such as
      marathon, trail, and ultra-trail races.

PMID- 29356950
TI  - The reliability of methods to estimate the number and size of human motor units
      and their use with large limb muscles.
AB  - PURPOSE: Current methods for estimating muscle motor unit (MU) number provide
      values which are remarkably similar for muscles of widely differing size,
      probably because surface electrodes sample from similar and relatively small
      volumes in each muscle. We have evaluated an alternative means of estimating MU
      number that takes into account differences in muscle size. METHODS: Intramuscular
      motor unit potentials (MUPs) were recorded and muscle cross-sectional area (CSA)
      was measured using MRI to provide a motor unit number estimate (iMUNE). This was
      compared to the traditional MUNE method, using compound muscle action potentials
      (CMAP) and surface motor unit potentials (sMUPs) recorded using surface
      electrodes. Data were collected from proximal and distal regions of the vastus
      lateralis (VL) in young and old men while test-retest reliability was evaluated
      with VL, tibialis anterior and biceps brachii. RESULTS: MUPs, sMUPs and CMAPs
      were highly reliable (r = 0.84-0.91). The traditional MUNE, based on surface
      recordings, did not differ between proximal and distal sites of the VL despite
      the proximal CSA being twice the distal CSA. iMUNE, however, gave values that
      differed between young and old and were proportional to the muscle size.
      CONCLUSION: When evaluating the contribution that MU loss makes to muscle
      atrophy, such as in disease or ageing, it is important to have a method such as
      iMUNE, which takes into account any differences in total muscle size.

PMID- 29356951
TI  - Partial and Full-Thickness RCT: Modern Repair Techniques.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review the recent literature
      concerning modern repair techniques related to partial- and full-thickness
      rotator cuff tears. RECENT FINDINGS: The understanding of rotator cuff pathology
      and healing continues to evolve, beginning with emerging descriptions of the
      anatomic footprint and natural history of rotator cuff tears. Significant
      controversy remains in treatment indications for partial-thickness rotator cuff
      lesions as well as optimal surgical repair techniques for both partial- and full
      thickness tears. Techniques such as margin convergence and reduction of the so
      called "comma" tissue have improved the ability to anatomically reduce large and
      retracted tears. Repair strength and contact pressures are improved with double
      row repairs and transosseus-equivalent techniques compared to traditional single
      row repairs. Future work is directed towards obtaining reliable radiographic
      healing and demonstrating clinical superiority and cost-effectiveness of a single
      technique. Much recent work regarding rotator cuff anatomy and pathology has been
      reported. Newer techniques improve repair strength. Despite these advances,
      significant questions remain concerning surgical indications and clinical
      outcomes.

PMID- 29356953
TI  - The use of PIPAC (pressurized intraperitoneal aerosol chemotherapy) in
      gynecological oncology: a statement by the German "Arbeitsgemeinschaft
      Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR)", the Swiss
      and Austrian AGO, and the North-Eastern German Society of Gynaecologic Oncology.
AB  - BACKGROUND: Ovarian, tubal, and peritoneal carcinomas primarily affect the
      peritoneal cavity, and they are typically diagnosed at an advanced tumor stage
      (Foley, Rauh-Hain, del Carmen in Oncology (Williston Park) 27:288-294, 2013). In
      the course of primary surgery, postoperative tumor residuals are, apart from the
      tumor stage, the strongest independent factors of prognosis (du Bois, Reuss,
      Pujade-Lauraine, Harter, Ray-Coquard, Pfisterer in Cancer 115:1234-1244, 2009).
      Due to improved surgical techniques, including the use of multi-visceral
      procedures, macroscopic tumor clearance can be achieved in oncological centers,
      in most cases (Harter, Muallem, Buhrmann et al in Gynecol Oncol 121:615-619,
      2011). However, to date, it has not been shown that peritoneal carcinomatosis is,
      per se, an independent factor of prognosis or that it excludes the achievement of
      tumor clearance. Several studies have shown that a preceding drug therapy in
      peritoneal carcinomatosis could positively influence the overall prognosis
      (Trimbos, Trimbos, Vergote et al in J Natl Cancer Inst 95:105-112, 2003). In
      relapses of ovarian carcinoma, studies have shown that peritoneal carcinomatosis
      is a negative predictor of complete tumor resection; however, when it is possible
      to resect the tumor completely, peritoneal carcinomatosis does not play a role in
      the prognosis (Harter, Hahmann, Lueck et al in Ann Surg Oncol 16:1324-1330,
      2009). RESULTS: PIPAC is a highly experimental method for treating patients with
      ovarian, tubal, and peritoneal cancer. To date, only three studies have
      investigated a total of 184 patients with peritoneal carcinomatosis (Grass,
      Vuagniaux, Teixeira-Farinha, Lehmann, Demartines, Hubner in Br J Surg 104:669
      678, 2017). Only some of those studies were phase I/II studies that included
      PIPAC for patients with different indications and different cancer entities. It
      is important to keep in mind that the PIPAC approach is associated with
      relatively high toxicity. To date, no systematic dose-finding studies have been
      reported. Moreover, no studies have reported improvements in progression-free or
      overall survival associated with PIPAC therapy. CONCLUSIONS: Randomized phase III
      studies are required to evaluate the effect of this therapy compared to other
      standard treatments (sequential or simultaneous applications with systemic
      chemotherapy). In cases of ovarian, tubal, and peritoneal cancer, PIPAC should
      not be performed outside the framework of prospective, controlled studies.

PMID- 29356952
TI  - Massive Rotator Cuff Tear: When to Consider Reverse Shoulder Arthroplasty.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss the indications for
      reverse shoulder arthroplasty (RSA) in the treatment of massive rotator cuff tear
      (MCT), review the reported outcomes in the literature, and outline our approach
      and surgical technique for treating these patients. RECENT FINDINGS: While RSA
      remains a successful and well-accepted treatment for cuff tear arthropathy (CTA),
      management of MCT in the absence of arthritis is controversial. In this
      particular setting, patients best suited for RSA are elderly, lower-demand
      individuals with chronic, irreparable MCT, and pseudoparalysis. Age < 60, better
      pre-operative function and upper extremity neurologic dysfunction are potential
      risk factors for poor outcome with RSA in this population. Long-term follow-up
      studies of RSA for CTA and MCT show good functional outcomes and implant survival
      > 90% at 10 years. Treatment of MCT must be individualized for each patient. When
      patient selection is optimized, RSA is a reliable means of relieving pain and
      improving function with excellent success. Further investigation is necessary to
      better define its indications and assess the role of alternative, joint-salvaging
      procedures.

PMID- 29356954
TI  - Frequency distribution of HLA alleles and haplotypes in Uyghur women with
      advanced squamous cell cervical cancer and relation to HPV status and clinical
      outcome.
AB  - PURPOSE: This study aims to investigate the association of human leukocyte
      antigen (HLA) alleles and haplotypes in Uyghur women with advanced squamous cell
      cervical cancer (SCC). METHODS: A total of 131 Uyghur patients with advanced SCC
      (IIb-IVa) and 91 healthy subjects from Xinjiang province were genotyped for HLA-I
      and II genes using Polymerase Chain Reaction Sequence Based Typing. The different
      frequencies of HLA alleles and haplotypes between patients and controls were
      compared and the correlations were analyzed between HLA distribution and HPV
      status and prognosis. RESULTS: (1) The frequencies of B*51:01, DRB1*07:01,
      DQB1*02:01, A*01:01-C*06:02, A*01:01-DRB1*07:01, C*06:02-DQB1*02:01, DRB1*07:01
      DQB1*02:01 and C*06:02-DRB1*07:01-DQB1*02:01 in cancer group were higher than
      control group whereas the frequencies of B*44:02, B*58:01, C*05:01, DRB1*04:01,
      DRB1*12:01, DRB1*13:01, DQB1*02:02, DQB1*05:02, DRB1*03:01-DQB1*02:02 and
      DRB1*04:01-DQB1*03:02 in cancer group were lower than control group (P < 0.05).
      (2) The frequencies of A*01:01-C*06:02, A*01:01-DRB1*07:01, C*06:02-DQB1*02:01,
      DRB1*07:01-DQB1*02:01 and C*06:02-DRB1*07:01-DQB1*02:01 in HPV positive group
      were lower than HPV negative group, differences of which were statistically
      significant (P < 0.05). (3) B*44:02 and B*58:01 were associated with reduced
      disease-specific survival (DSS) (P = 0.010 and 0.007). (4) Multivariate Cox
      proportional hazard models revealed that age, International Federation of
      Gynaecology and Obstetrics (FIGO) stage, tumor differentiation and allele B*58:01
      as independent predictors for DSS while FIGO stage and tumor differentiation as
      independent factors for DFS. CONCLUSIONS: In the development and progression of
      advanced SCC among Uyghur population, the HLA alleles and its haplotypes play an
      important role. B*58:01 allele may act as an independent predictor for DSS.

PMID- 29356955
TI  - Trial of labor following one previous cesarean delivery: the effect of
      gestational age.
AB  - PURPOSE: To stratify maternal and neonatal outcomes of trials of labor after
      previous cesarean delivery (TOLAC) by gestational age. METHODS: Retrospective
      cohort study of all singleton pregnancies with one previous cesarean delivery in
      TOLAC at term between 2007 and 2014. We compared outcomes of delivery at an index
      gestational week, with outcomes of women who remained undelivered at this index
      gestational week (ongoing pregnancy). Odds ratios and 95% confidence intervals
      were adjusted for maternal age, previous vaginal delivery, induction of labor,
      epidural use, presence of meconium, and birth weight > 4000 g. RESULTS: Overall,
      2849 women were eligible for analysis. Of those, 2584 (90.7%) had a successful
      TOLAC and 16 women (0.56%) had uterine rupture. Those rates did not differ
      significantly for any gestational age (GA) group. Following adjustment for
      possible confounders, GA was not found to be independently associated with
      adverse maternal or neonatal outcomes. CONCLUSION: Among women at term with a
      single previous cesarean delivery, GA at delivery was not found to be an
      independent risk factor for TOLAC success or uterine rupture. We suggest that GA
      by itself will not serve as an argument for or against TOLAC.

PMID- 29356957
TI  - Recurrent stroke-like episodes of Wilson disease with a novel Val176fs mutation.

PMID- 29356956
TI  - Paediatric Patients with Coeliac Disease on a Gluten-Free Diet: Nutritional
      Adequacy and Macro- and Micronutrient Imbalances.
AB  - PURPOSE OF REVIEW: A strict, lifelong gluten-free diet is the cornerstone for
      management of coeliac disease. Elimination of gluten from the diet may be
      associated with nutritional imbalance; however, the completeness of this diet in
      energy and macro- and micronutrients in children is not well described.
      Understanding the nutritional adequacy of the gluten-free diet in children during
      this critical period of growth and development when dietary intake is strongly
      influential is important. RECENT FINDINGS: Children, regardless of whether they
      have eliminated gluten from their diet, have a tendency to consume excess fat and
      insufficient fibre, iron, vitamin D and calcium, compared to recommendations. In
      the context of a gluten-free diet, these imbalances may be worsened or have more
      significant consequences. Paediatric studies have demonstrated that intakes of
      folate, magnesium, zinc and selenium may decrease on a gluten-free diet.
      Nutritional inadequacies may be risks of a gluten-free diet in a paediatric
      population. The potential implications of these inadequacies, both short and long
      term, remain unclear and warrant further investigation and clarification.

PMID- 29356958
TI  - Comparison between a nurse-led weaning protocol and weaning based on physician's
      clinical judgment in tracheostomized critically ill patients: a pilot randomized
      controlled clinical trial.
AB  - BACKGROUND: Weaning protocols expedite extubation in mechanically ventilated
      patients, yet the literature investigating the application in tracheostomized
      patients remains scarce. The primary objective of this parallel randomized
      controlled pilot trial (RCT) was to assess the feasibility and safety of a nurse
      led weaning protocol (protocol) compared to weaning based on physician's clinical
      judgment (control) in tracheostomized critically ill patients. RESULTS: We
      enrolled 65 patients, 27 were in the protocol group and 38 in the control group.
      Of 27 patients in the protocol group, 1 (3.7%) died in the ICU, 24 (88.9%) were
      successfully weaned from tracheostomy, and 2 (7.4%) were transferred still on the
      ventilator. Of 38 patients in the control group, 2 (5.3%) died in the ICU, 22
      (57.9%) were successfully weaned from tracheostomy, and 14 were transferred still
      on the ventilator (36.8%). Risk of being discharged from the ICU on the
      ventilator was higher in the control group (relative risk: 1.5, IC 95% 1.14
      2.01). Concerning safety and feasibility, no patients were excluded after
      randomization. There was no crossover between the two study arms nor missing
      data, and no severe adverse event related to the study protocol application was
      recorded by the staff. Weaning time and rate of successful weaning were not
      different in the protocol group compared to the control group (long-rank test, p
      = 0.31 for MV duration, p = 0.45 for weaning time). Based on our results and
      assuming a 30% reduction of the weaning time for the protocol group, 280 patients
      would be needed for a RCT to establish efficacy. CONCLUSIONS: In this pilot RCT
      we demonstrated that a nurse-led weaning protocol from tracheostomy was feasible
      and safe. A larger RCT is justified to assess efficacy.

PMID- 29356959
TI  - Hepatic portal venous gas due to polystyrene sulfonate-induced enteritis.
AB  - A 78-year-old man with acute right lower abdominal pain and nausea was referred
      to our hospital. Computed tomography (CT) demonstrated hepatic portal venous gas
      and a thickened wall of the terminal ileum, and colonoscopy demonstrated ulcers
      and erosions of the ileocecal region. Histological examination of biopsy samples
      revealed basophilic crystals consistent with the component of calcium polystyrene
      sulfonate (CPS). This patient started taking CPS 2 months prior for chronic
      hyperkalemia. The symptoms resolved soon after ceasing CPS, and subsequent
      imaging studies confirmed the disappearance of the portal venous gas and
      ileocolitis.

PMID- 29356960
TI  - Headache following head injury: a population-based longitudinal cohort study
      (HUNT).
AB  - BACKGROUND: Headache is the most frequent symptom following head injury, but long
      term follow-up of headache after head injury entails methodological challenges.
      In a population-based cohort study, we explored whether subjects hospitalized due
      to a head injury more often developed a new headache or experienced exacerbation
      of previously reported headache compared to the surrounding population. METHODS:
      This population-based historical cohort study included headache data from two
      large epidemiological surveys performed with an 11-year interval. This was linked
      with data from hospital records on exposure to head injury occurring between the
      health surveys. Participants in the surveys who had not been hospitalized because
      of a head injury comprised the control group. The head injuries were classified
      according to the Head Injury Severity Scale (HISS). Multinomial logistic
      regression was performed to investigate the association between head injury and
      new headache or exacerbation of pre-existing headache in a population with known
      pre-injury headache status, controlling for potential confounders. RESULTS: The
      exposed group consisted of 294 individuals and the control group of 25,662
      individuals. In multivariate analyses, adjusting for age, sex, anxiety,
      depression, education level, smoking and alcohol use, mild head injury increased
      the risk of new onset headache suffering (OR 1.74, 95% CI 1.05-2.87), stable
      headache suffering (OR 1.70, 95% CI 1.15-2.50) and exacerbation of previously
      reported headache (OR 1.93, 95% CI 1.24-3.02). The reference category was
      participants without headache in both surveys. CONCLUSION: Individuals
      hospitalized due to a head injury were more likely to have new onset and
      worsening of pre-existing headache and persistent headache, compared to the
      surrounding general population. The results support the entity of the ICHD-3 beta
      diagnosis "persistent headache attributed to traumatic injury to the head".

PMID- 29356962
TI  - Growth plate-derived hedgehog-signal-responsive cells provide skeletal tissue
      components in growing bone.
AB  - Longitudinal bone growth progresses by continuous bone replacement of epiphyseal
      cartilaginous tissue, known as "growth plate", produced by columnar proliferated-
      and differentiated-epiphyseal chondrocytes. The endochondral ossification process
      at the growth plate is governed by paracrine signals secreted from terminally
      differentiated chondrocytes (hypertrophic chondrocytes), and hedgehog signaling
      is one of the best known regulatory signaling pathways in this process. Here, to
      investigate the developmental relationship between longitudinal endochondral bone
      formation and osteogenic progenitors under the influence of hedgehog signaling at
      the growth plate, genetic lineage tracing was carried out with the use of
      Gli1CreERT2 mice line to follow the fate of hedgehog-signal-responsive cells
      during endochondral bone formation. Gli1CreERT2 genetically labeled cells are
      detected in hypertrophic chondrocytes and osteo-progenitors at the chondro
      osseous junction (COJ); these progeny then commit to the osteogenic lineage in
      periosteum, trabecular and cortical bone along the developing longitudinal axis.
      Furthermore, in ageing bone, where longitudinal bone growth ceases, hedgehog
      signal responsiveness and its implication in osteogenic lineage commitment is
      significantly weakened. These results show, for the first time, evidence of the
      developmental contribution of endochondral progenitors under the influence of
      epiphyseal chondrocyte-derived secretory signals in longitudinally growing bone.
      This study provides a precise outline for assessing the skeletal lineage
      commitment of osteo-progenitors in response to growth-plate-derived regulatory
      signals during endochondral bone formation.

PMID- 29356961
TI  - Runx2, an inducer of osteoblast and chondrocyte differentiation.
AB  - Runx2 is a transcription factor that is essential for osteoblast differentiation
      and chondrocyte maturation. Ihh, expressed in prehypertrophic and hypertrophic
      chondrocytes, is required for the specification of Runx2+ osteoprogenitors in
      endochondral bone development. Runx2 induces Sp7, an essential transcription
      factor for osteoblast differentiation. Canonical Wnt signaling is also required
      for osteoblast differentiation. Runx2+ osteoprogenitors retain the capacity to
      differentiate into chondrocytes, and Sp7 and canonical Wnt signaling direct cells
      to osteoblasts, thereby inhibiting chondrocyte differentiation. The function of
      Runx2 after the commitment to osteoblasts remains controversial. Runx3 has a
      redundant function with Runx2 in chondrocyte maturation. Runx2 regulates the
      expression of Ihh, Col10a1, Spp1, Ibsp, Mmp13, and Vegfa in the respective layers
      in growth plates. Runx2 enhances chondrocyte proliferation through the induction
      of Ihh. Ihh induces Pthlh, which inhibits Runx2 and chondrocyte maturation,
      forming a negative feedback loop for chondrocyte maturation. Runx2 is one of the
      genes responsible for the pathogenesis of osteoarthritis (OA) because RUNX2 is up
      regulated in chondrocytes in OA cartilage and a germline haplodeficiency or
      deletion of Runx2 in articular chondrocytes decelerates OA progression. Runx2
      plays an important role in the bone metastasis of breast and prostate cancers by
      up-regulating Spp1, Ibsp, Mmp9, Mmp13, Vegfa, Tnfsf11, and Ihh expression and
      down-regulating Tnfrsf11b expression. Cbfb forms a heterodimer with Runx2 and is
      required for the efficient DNA binding of Runx2. Cbfb stabilizes Runx proteins at
      different levels among Runx family proteins by inhibiting their ubiquitination
      mediated degradation. Cbfb plays more important roles in endochondral
      ossification than in intramembranous ossification.

PMID- 29356963
TI  - Pathologic conditions of hard tissue: role of osteoclasts in osteolytic lesion.
AB  - Hard tissue homeostasis is regulated by the balance between bone formation by
      osteoblasts and bone resorption by osteoclasts. This physiologic process allows
      adaptation to mechanical loading and calcium homeostasis. Under pathologic
      conditions, however, this process is ill-balanced resulting in either over
      resorption or over-formation of hard tissue. Local over-resorption by osteoclasts
      is typically observed in osteolytic metastases of malignancies, autoimmune
      arthritis, and giant cell tumor of bone (GCTB). In tumor-related local
      osteolysis, tumor-derived osteoclast-activating factors induce bone resorption
      not by directly acting on osteoclasts but by indirectly upregulating receptor
      activator of NFkappaB ligand (RANKL) on osteoblastic cells. Similarly, synovial
      tissue in the autoimmune arthritis model does overexpress RANKL and contains
      numerous osteoclast precursors, and like a landing craft, when it comes in
      contact with eroded bone surfaces, osteoclast precursors are immediately
      polarized to become mature osteoclasts, inducing rapidly progressive bone
      destruction at a late stage of the disease. GCTB, on the other hand, is a common
      primary bone tumor, usually arising at the metaphysis of the long bone in young
      adults. After the discovery of RANKL, the concept of GCTB as a tumor of RANKL
      expressing stromal cells was established, and comprehensive exosome studies
      finally disclosed the causative single-point mutation at histone H3.3 (H3F3A) in
      stromal cells. Thus, osteolytic lesions under various pathological conditions are
      ultimately attributable to the overexpression of RANKL, which opens up a common,
      practical and useful therapeutic target for diverse osteolytic conditions.

PMID- 29356964
TI  - Histomorphometric analyses of human adipose tissues using intact, flash-frozen
      samples.
AB  - Histomorphometric analyses of adipose tissue usually require formalin fixation of
      fresh samples. Our objective was to determine if intact, flash-frozen whole
      adipose tissue samples stored at - 80  degrees C could be used for measurements
      developed for fresh-fixed adipose tissues. Portions of adipose tissue samples
      were either formalin-fixed immediately upon sampling or flash-frozen and stored
      at - 80  degrees C and then formalin-fixed during the thawing process. Mean
      adipocyte diameter was measured. Immunohistochemistry was performed on additional
      samples to identify macrophage subtypes (M1, CD14 + and M2, CD206 +) and total
      (CD68 +) number. All slides were counterstained using haematoxylin and eosin
      (H&E). Visual inspection of H&E-stained adipose tissue slides performed in a
      blinded fashion showed little or no sign of cell breakage in 74% of frozen-fixed
      samples and in 68% of fresh-fixed samples (p > 0.5). There was no difference in
      the distribution frequencies of adipocyte sizes in fresh-fixed vs. frozen-fixed
      tissues in both depots (p > 0.9). Mean adipocyte size from frozen-fixed samples
      correlated significantly and positively with adipocyte size from fresh-fixed
      samples (r = 0.74, p < 0.0001, for both depots). The quality of
      staining/immunostaining and appearance of tissue architecture were comparable in
      fresh-fixed vs. frozen-fixed samples. In conclusion, intact flash-frozen adipose
      tissue samples stored at - 80  degrees C can be used to perform techniques
      conventionally applied to fresh-fixed samples. This approach allows for
      retrospective studies with frozen human adipose tissue samples.

PMID- 29356965
TI  - NKG2D ligands in glioma stem-like cells: expression in situ and in vitro.
AB  - Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Tumor stem cells
      have a major influence on tumor malignancy, and immunological escape mechanisms,
      involving the Natural Killer Group 2, member D (NKG2D) receptor-ligand-system,
      are key elements in tumor immuno-surveillance. We analyzed the expression profile
      and localization of NKG2D ligands (NKG2DL) and embryonic and neural stem cell
      markers in solid human GBM and stem-like cells isolated from glioma cell lines by
      qRT-PCR and immunohistochemistry, including quantitative analysis. We also
      evaluated the effect of Temozolomide (TMZ), the standard chemotherapeutic agent
      used in GBM therapy, on NKG2DL expression. NKG2DL-positive cells were mostly
      found scattered and isolated, were detectable in glial fibrillary acidic protein
      (GFAP)-positive tumor regions and partly in the penumbra of tumor vessels. NKG2DL
      were found in a distinct tumor stem-like cell subpopulation and were broadly
      costained with each other. Quantitative analysis revealed, that dependent on the
      individual NKG2DL investigated, cell portions costained with different stem cell
      markers varied between small (Musashi-1) and high (KLf-4) amounts. However, a
      costaining of NKG2DL with CD3gamma, typically found in T cells, was also
      observable, whereas CD11b as a marker for tumor micoglia cells was only rarely
      costained with NKG2DL. Stem-like cells derived from the glioma cell lines T98G
      and U251MG showed a distinct expression pattern of NKG2DL and stem cell markers,
      which seemed to be balanced in a cell line-specific way. With differentiation,
      T98G displayed less NKG2DL, whereas in U251MG, only expression of most stem cell
      markers decreased. In addition, stimulation with TMZ led to a significant
      upregulation of NKG2DL in stem-like cells of both lines. As stem-like glioma
      cells tend to show a higher expression of NKG2DL than more differentiated tumor
      cells and TMZ treatment supports upregulation of NKG2DL, the NKG2D system might
      play an important role in tumor stem cell survival and in GBM therapy.

PMID- 29356966
TI  - Pheochromocytomas and Hypertension.
AB  - PURPOSE OF REVIEW: Pheochromocytomas and paragangliomas (PPGLs) are uncommon
      catecholamine-producing neuroendocrine neoplasms that usually present with
      secondary hypertension. This review is to update the current knowledge about
      these neoplasms, the pathophysiology, genetic aspects and diagnostic and
      therapeutic algorithms based on scientific literature mostly within the past 3
      years. RECENT FINDINGS: Eighty to eighty-five percent of PPGLs arise from the
      adrenal medulla (pheochromocytomas; PCCs) and the remainder from the autonomic
      neural ganglia (paragangliomas; PGLs). Catecholamine excess causes chronic or
      paroxysmal hypertension associated with sweating, headaches and palpitations, the
      presenting features of PPGLs, and increases the cardiovascular morbidity and
      mortality. Genetic testing should be considered in all cases as mutations are
      reported in 35-40% of cases; 10-15% of PCCs and 20-50% of PGLs can be malignant.
      Measurements of plasma-free metanephrines or 24-h urine-fractionated
      metanephrines help biochemical diagnosis with high sensitivity and specificity.
      Initial anatomical localization after biochemical confirmation is usually with
      computed tomography (CT) or magnetic resonance imaging (MRI). 123Iodine
      metaiodobenzylguanidine (123I-MIBG) scintigraphy, positron emission tomography
      (PET) or single-photon emission computed tomography (SPECT) is often performed
      for functional imaging and prognostication prior to curative or palliative
      surgery. Clinical and biochemical follow-up is recommended at least annually
      after complete tumour excision. Children, pregnant women and older people have
      higher morbidity and mortality risk. De-bulking surgery, chemotherapy,
      radiotherapy, radionuclide agents and ablation procedures are useful in the
      palliation of incurable disease. PPGLs are unique neuroendocrine tumours that
      form an important cause for endocrine hypertension. The diagnostic and
      therapeutic algorithms are updated in this comprehensive article.

PMID- 29356967
TI  - Sporadic late-onset nemaline myopathy: clinical, pathology and imaging findings
      in a single center cohort.
AB  - Sporadic late-onset nemaline myopathy (SLONM) is a rare acquired myopathy
      characterized by rapid-onset proximal weakness in late adulthood, and the
      presence of nemaline bodies on muscle biopsy. In recent years, several
      therapeutic interventions, including immunomodulating agents and autologous stem
      cell transplantation, have shown variable degrees of efficacy in different
      patients, but no consensus has been reached to allow an effective tailoring of
      treatments in this severe disease. We performed a retrospective evaluation of
      clinical, pathological, laboratory, muscle MRI, and follow-up data of SLONM
      patients diagnosed in the period 2010-2015 in our neuromuscular center. Six
      patients (three males and three females) were identified. Average time elapsed
      from the onset of symptoms to referral to the neuromuscular specialist was 23.7
      months. Monoclonal gammopathy was detectable in five patients. Nemaline bodies
      were detected in all the patients, and their abundance correlated with clinical
      severity. Signs of cardiac involvement were present in all the patients to
      different extents. Muscle MRI showed a preferential involvement of neck
      extensors, paraspinal, gluteal, hamstring and soleus muscles. All patients were
      treated with prednisone and repeated courses of intravenous immunoglobulins, and
      a favorable outcome was reached in five patients. Our experience confirms that
      SLONM is clinically characterized by subacute proximal and axial muscle weakness.
      Time to referral was relatively long and should be reduced with increasing
      awareness of the disease. Muscle MRI could be of help as a diagnostic tool to
      identify this potentially treatable myopathy. Cardiac evaluation should be
      warranted in all SLONM patients to detect subclinical heart involvement.

PMID- 29356968
TI  - Low signal intensity in motor cortex on susceptibility-weighted MR imaging is
      correlated with clinical signs of amyotrophic lateral sclerosis: a pilot study.
AB  - There is no reliable objective indicator for upper motor neuron dysfunction in
      amyotrophic lateral sclerosis (ALS). To determine the clinical significance and
      potential utility of magnetic resonance (MR) signals, we investigated the
      relationship between clinical symptoms and susceptibility changes in the motor
      cortex measured using susceptibility-weighted MR imaging taken by readily
      available 3-T MRI in clinical practice. Twenty-four ALS patients and 14 control
      subjects underwent 3-T MR T1-weighted imaging and susceptibility-weighted MR
      imaging with the principles of echo-shifting with a train of observations
      (PRESTO) sequence. We analysed relationships between relative susceptibility
      changes in the motor cortex assessed using voxel-based analysis (VBA) and
      clinical scores, including upper motor neuron score, ALS functional rating scale
      revised score, and Medical Research Council sum score on physical examination.
      Patients with ALS exhibited significantly lower signal intensity in the
      precentral gyrus on susceptibility-weighted MR imaging compared with controls.
      Clinical scores were significantly correlated with susceptibility changes.
      Importantly, the extent of the susceptibility changes in the bilateral precentral
      gyri was significantly correlated with upper motor neuron scores. The results of
      our pilot study using VBA indicated that low signal intensity in motor cortex on
      susceptibility-weighted MR imaging may correspond to clinical symptoms,
      particularly upper motor neuron dysfunction. Susceptibility-weighted MR imaging
      may be a useful diagnostic tool as an objective indicator of upper motor neuron
      dysfunction.

PMID- 29356969
TI  - Johann Paul Karplus (1866-1936).

PMID- 29356970
TI  - Cognitive phenotypes in multiple sclerosis.
AB  - BACKGROUND: Cognitive impairment is a debilitating symptom experienced by ~ 50%
      of multiple sclerosis patients, with processing speed (PS) and memory most
      affected. Until now, the field has considered cognition in a binary fashion:
      patients are designated as impaired or not impaired. This designation is
      typically arrived at by administering a full cognitive battery and assigning a
      cutoff (e.g., 4 of 11 tests failed) to distinguish impaired/non-impaired. This
      relatively coarse approach yields a heterogeneous group of "impaired" patients,
      some of whom may have isolated memory or PS deficits, others with combined
      deficits. The goal of this study is to determine whether predominant patterns of
      deficits, "cognitive phenotypes", can be identified in a large sample of MS
      patients. Proportional representation of four cognitive phenotypes will be
      evaluated: (1) not impaired, (2) PS-impaired only, (3) memory-impaired only, (4)
      PS + memory impaired. METHODS: Cognition was measured in 128 relapsing-remitting
      MS patients using validated tests of verbal/visual memory, and PS. Cognitive
      phenotype representation was evaluated. Differences in age, education, disease
      duration, and IQ across cognitive phenotype groups were evaluated. RESULTS: Four
      cognitive phenotype groups were represented: 56.3% not impaired, 7.8% PS
      impaired, 18.8% memory-impaired, 17.2% PS + memory impaired. Across groups, there
      were no differences in age, education, disease duration. IQ in non-impaired was
      higher than PS + memory impaired. CONCLUSIONS: Adopting a novel classification
      taxonomy for cognitive phenotypes will advance understanding of cognitive
      impairment and enable a precision medicine approach to the development of
      effective, targeted treatments for cognition in persons with MS.

PMID- 29356972
TI  - Patent foramen ovale closure versus medical therapy in cases with cryptogenic
      stroke, meta-analysis of randomized controlled trials.
AB  - BACKGROUND: PFO is more common in cases with cryptogenic stroke compared to cases
      with no stroke or stroke of identified etiology. Several randomized controlled
      trials (RCTs) comparing PFO closure with medical therapy have been published with
      controversial findings. METHODS: PubMed, Embase and Cochrane library databases
      were searched for RCT comparing PFO closure with medical therapy including
      antiplatelet therapy (aspirin or clopidogrel or combination) or anticoagulation.
      We identified 5 trials, including 3627 cases. The mean duration of follow-up was
      4 years. Relative risk (RR) and 95% confidence intervals (CI) were calculated
      using fixed and random-effects models. RESULTS: There was a significant reduction
      in the incidence of stroke among the PFO closure group compared to medical
      therapy group, 2.0 versus 4.2%, RR 0.48; 95% CI (0.3, 0.7), p < 0.001. The
      incidence of AF was higher in the PFO closure group compared to medical therapy
      group, 4.2 versus 0.7%, respectively, RR 5.9, 95% CI (3, 11), p < 0.001. After
      exclusion of oral anticoagulants cases (19%), analysis showed a lower incidence
      of stroke in the PFO closure group (2%) compared to antiplatelet therapy (5.2%),
      RR 0.4; 95% CI (0.3, 0.6), p < 0.001. There was no significant difference between
      both groups in the incidence of transient ischemic attacks or all-cause deaths.
      CONCLUSION: PFO closure results in a significant reduction in the recurrence of
      ischemic stroke compared to medical therapy alone, primarily antiplatelet, among
      cases with PFO and cryptogenic stroke.

PMID- 29356971
TI  - Pathological examination of cerebral amyloid angiopathy in patients who underwent
      removal of lobar hemorrhages.
AB  - Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by
      amyloid-beta (Abeta) deposition in the brain microvessels. CAA is also known to
      contribute not only to cortical microbleeds but also lobar hemorrhages. This
      retrospective study examined CAA pathologically in patients who underwent direct
      surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage
      underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical
      tissues over hematomas obtained surgically were pathologically examined using
      hematoxylin, eosin stain, and anti-Abeta antibody to diagnose CAA. We also
      investigated the advanced degree of CAA and clinical features of each patient
      with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were
      insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29
      patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA
      positive patients had moderate or severe CAA based on a grading scale to estimate
      the advanced degree of CAA. About half of the CAA-positive patients had
      hypertension, and four took anticoagulant or antiplatelet agents. In five
      patients who were not pathologically diagnosed with CAA, one had severe liver
      function disorder, three had uncontrollable hypertension, and one had no obvious
      risk factor. Our pathological findings suggest that severe CAA with vasculopathic
      change markedly contributes to lobar hemorrhage. The coexistence of severe CAA
      and risk factors such as hypertension, anticoagulants or antiplatelets may
      readily induce lobar hemorrhage.

PMID- 29356973
TI  - Pitfalls in clinical diagnosis of anti-NMDA receptor encephalitis.
AB  - OBJECTIVES: To report pitfalls in the clinical diagnosis of anti-N-methyl-D
      aspartate receptor (NMDAR) encephalitis. METHODS: We retrospectively reviewed the
      clinical information of 221 patients with clinically suspected autoimmune
      neurological disorders who underwent testing for autoantibodies against neuronal
      cell-surface antigens between January 1, 2007 and September 10, 2017. Forty-one
      patients met the diagnostic criteria for probable anti-NMDAR encephalitis
      (probable criteria), but one was excluded because neither serum nor CSF was
      examined at the active stage. Thus, in 220 patients, sensitivity and specificity
      of the probable criteria were assessed. RESULTS: NMDAR-antibodies were detected
      in 34 of 40 patients (85%) with the probable criteria; however, 2 of the 6
      antibody-negative patients had ovarian teratoma. The median age at onset was
      higher in antibody-negative patients than those with antibodies (49 vs. 27 years,
      p = 0.015). The age at onset was associated with the probability of antibody
      detection (p = 0.014); the probability was less than 50% in patients aged 50
      years or older. NMDAR-antibodies were also detected in 5 of 180 patients who did
      not fulfill the probable criteria; these patients presented with isolated
      epileptic syndrome (n = 2), atypical demyelinating syndrome (n = 2; one with
      aquaporin 4 antibodies), and autoimmune post-herpes simplex encephalitis (post
      HSE) (n = 1). Sensitivity and specificity of the probable criteria was 87.2 and
      96.7%, respectively. CONCLUSION: The probable criteria are valid, but the
      diversity of clinical phenotype should be taken into account in diagnosing anti
      NMDAR encephalitis particularly in patients aged 50 years or older, or with
      isolated epileptic syndrome, atypical demyelinating syndrome, or post-HSE.

PMID- 29356976
TI  - Scribonius Largus (probably before 1CE-after 48CE).

PMID- 29356974
TI  - Structural cerebellar correlates of cognitive functions in spinocerebellar ataxia
      type 2.
AB  - Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative
      disease involving the cerebellum and characterized by a typical motor syndrome.
      In addition, the presence of cognitive impairment is now widely acknowledged as a
      feature of SCA2. Given the extensive connections between the cerebellum and
      associative cerebral areas, it is reasonable to hypothesize that cerebellar
      neurodegeneration associated with SCA2 may impact on the cerebellar modulation of
      the cerebral cortex, thus resulting in functional impairment. The aim of the
      present study was to investigate and quantitatively map the pattern of cerebellar
      gray matter (GM) atrophy due to SCA2 neurodegeneration and to correlate that with
      patients' cognitive performances. Cerebellar GM maps were extracted and compared
      between SCA2 patients (n = 9) and controls (n = 33) by using voxel-based
      morphometry. Furthermore, the relationship between cerebellar GM atrophy and
      neuropsychological scores of the patients was assessed. Specific cerebellar GM
      regions were found to be affected in patients. Additionally, GM loss in cognitive
      posterior lobules (VI, Crus I, Crus II, VIIB, IX) correlated with visuospatial,
      verbal memory and executive tasks, while additional correlations with motor
      anterior (V) and posterior (VIIIA, VIIIB) lobules were found for the tasks
      engaging motor and planning components. Our results provide evidence that the
      SCA2 neurodegenerative process affects the cerebellar cortex and that MRI indices
      of atrophy in different cerebellar subregions may account for the specificity of
      cognitive symptomatology observed in patients, as result of a cerebello-cerebral
      dysregulation.

PMID- 29356975
TI  - Electrophysiological and behavioral effects of frontal transcranial direct
      current stimulation on cognitive fatigue in multiple sclerosis.
AB  - Fatigue is one of the most common and debilitating symptoms affecting patients
      with multiple sclerosis (MS). Sustained cognitive effort induces cognitive
      fatigue, operationalized as subjective exhaustion and fatigue-related objective
      alertness decrements with time-on-task. During prolonged cognitive testing, MS
      patients show increased simple reaction times (RT) accompanied by lower
      amplitudes and prolonged latencies of the P300 event-related potential. Previous
      studies suggested a major role of structural and functional abnormalities in the
      frontal cortex including a frontal hypo-activation in fatigue pathogenesis. In
      the present study we investigated the neuromodulatory effect of transcranial
      direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex
      (DLPFC) on objective measures of fatigue-related decrements in cognitive
      performance in MS patients. P300 during an auditory oddball task and simple
      reaction times in an alertness test were recorded at baseline, during and after
      stimulation. Compared to sham, anodal tDCS caused an increase in P300 amplitude
      that persisted after the end of stimulation and eliminated the fatigue-related
      increase in RT over the course of a testing session. Our findings demonstrate
      that anodal tDCS over the left DLPFC can counteract performance decrements
      associated with fatigue thereby leading to an improvement in the patient's
      ability to cope with sustained cognitive demands. This provides causal evidence
      for the functional relevance of the left DLPFC in fatigue pathophysiology. The
      results indicate that tDCS-induced modulations of frontal activity can be an
      effective therapeutic option for the treatment of fatigue-related declines in
      cognitive performance in MS patients.

PMID- 29356978
TI  - Caribbean (English-Speaking) Women in the United States: Cooking for Diabetes
      Prevention and Management.
AB  - This study surveyed 152 Caribbean-American women about their acculturation
      levels; their health behaviors; and their perceptions about a website portal for
      diabetes prevention and management. Participants followed a study link to
      documents created via SurveyMonkey. The study link included seven edited videos
      each fewer than 2 min; the videos included ingredients; preparation/cooking
      instructions; and plating tips for modifying traditional Caribbean meals for
      diabetes management and prevention. Overall engagement in six healthy living
      behaviors was moderate Mean = 2.07; Minimum = 1 (Never); Maximum = 3.0 (Always).
      Self-efficacy for cooking 'healthy' before exploring the website was a mean 3.52
      between 40 and 60% confident (SD = 1.509) versus the after Mean of 4.59 closest
      to 80% confident (SD = 1.154); t = - 10.353, df = 147 (P < 0.001). The results
      suggest the website did serve as a brief intervention for increasing self
      efficacy in cooking meals more consistent with diabetes prevention and
      management.

PMID- 29356979
TI  - Analysis of US FDA-Approved Drugs Containing Sulfur Atoms.
AB  - In this review, we discuss all sulfur-containing FDA-approved drugs and their
      structures. The second section of the review is dedicated to structural analysis
      and is divided into 14 subsections, each focusing on one type of sulfur
      containing moiety. A concise graphical representation of each class features
      drugs that are organized on the basis of structural similarity, evolutionary
      relevance, and medical indication. This review offers a unique and comprehensive
      overview of the structural features of all sulfur-containing FDA-approved drugs
      to date.

PMID- 29356977
TI  - Short- and long-term clinical outcomes of use of beta-interferon or glatiramer
      acetate for people with clinically isolated syndrome: a systematic review of
      randomised controlled trials and network meta-analysis.
AB  - BACKGROUND: Beta-interferon (IFN-beta) and glatiramer acetate (GA) have been
      evaluated in people with clinically isolated syndrome (CIS) with the aim to delay
      a second clinical attack and a diagnosis of clinically definite multiple
      sclerosis (CDMS). We systematically reviewed trials evaluating the short- and
      long-term clinical effectiveness of these drugs in CIS. METHODS: We searched
      multiple electronic databases. We selected randomised controlled studies (RCTs)
      conducted in CIS patients and where the interventions were IFN-beta and GA. Main
      outcomes were time to CDMS, and discontinuation due to adverse events (AE). We
      compared interventions using random-effect network meta-analyses (NMA). We also
      reported outcomes from long-term open-label extension (OLE) studies. RESULTS: We
      identified five primary studies. Four had open-label extensions following double
      blind periods comparing outcomes between early vs delayed DMT. Short-term
      clinical results (double-blind period) showed that all drugs delayed CDMS
      compared to placebo. Indirect comparisons did not suggest superiority of any one
      active drug over another. We could not undertake a NMA for discontinuation due to
      AE. Long-term clinical results (OLE studies) showed that the risk of developing
      CDMS was consistently reduced across studies after early DMT treatment compared
      to delayed DMT (HR = 0.64, 95% CI 0.55, 0.74). No data supported the benefit of
      DMTs in reducing the time to, and magnitude of, disability progression.
      CONCLUSIONS: Meta-analyses confirmed that IFN-beta and GA delay time to CDMS
      compared to placebo. In the absence of evidence that early DMTs can reduce
      disability progression, future research is needed to better identify patients
      most likely to benefit from long-term DMTs.

PMID- 29356980
TI  - Vanillic acid attenuates cerebral hyperemia, blood-brain barrier disruption and
      anxiety-like behaviors in rats following transient bilateral common carotid
      occlusion and reperfusion.
AB  - Transient bilateral common carotid artery occlusion (tBCCAO), followed by
      reperfusion, is a model of transient global hypoperfusion. In the present study
      we aimed to investigate the probable effects of Vanillic acid (VA) on some
      physiological parameters including cerebral hyperemia, blood-brain barrier (BBB)
      disruption, anxiety behaviors and neurological deficits induced by bilateral
      occlusion of the common carotid arteries and reperfusion (BCCAO/R) in rats. Rats
      were randomly divided into four groups; Sham, BCCAO/R, VA and VA+ BCCAO/R.
      Chronic cerebral hypoperfusion was induced after 2 weeks of pretreatment by VA.
      Subsequently, sensorimotor scores, elevated plus maze tests, cerebral hyperemia,
      and BBB disruption were evaluated 72 h after 30 min of BCCAO. Pretreatment of
      rats by VA improved sensory motor signs, anxiolytic behavior in BCCAO/R rats
      compared with untreated rats (p < 0.05). Further, VA attenuated reactive
      hyperemia and BBB disruption in BCCAO/R rats compared with untreated rats (p <
      0.01). To our knowledge, this study is the first to reveal VA could attenuate
      reactive hyperemia and improve BBB disruption following BCCAO/R, and could
      improve neurological scores and anxiety like behaviors in this model of cerebral
      hypoperfusion. These results suggest that VA could be a promising pretreatment
      agent in cerebral hypoperfusion.

PMID- 29356982
TI  - Everything is ok on YouTube! Quality assessment of YouTube videos on the topic of
      phacoemulsification in eyes with small pupil.
AB  - OBJECTIVE: Usage of YouTube as an educational tool is gaining attention in
      academic research. To date, there has been no study on the content and quality of
      eye surgery videos on YouTube. The aim of this study was to analyze YouTube
      videos on phacoemulsification in eyes with small pupil. METHODS: We searched for
      the phrases "small pupil cataract surgery," "small pupil phacoemulsification,"
      "small pupil cataract surgery complications," and "small pupil
      phacoemulsification complications" in January 2015. Each resulting video was
      evaluated by all authors, and Krippendorff's alpha was calculated to measure
      agreement. Videos were classified according to pupil size (small/very small) in
      the beginning of the surgery, and whether pupillary diameter was large enough to
      continue surgery safely after pupillary dilation by the surgeon in the video
      (safe/not safe). Methods of dilatation were also analyzed. Any stated ocular
      comorbidity or surgical complications were noted. RESULTS: A total of 96 videos
      were reviewed. No mechanical intervention for pupillary dilatation was performed
      in 46 videos. Fifty-eight operated eyes had no stated ocular comorbidity. Ninety
      five operations ended successfully without major complication. There was fair
      agreement between the evaluators regarding pupil sizes (Kalpha = 0.670) but poor
      agreement regarding safety (Kalpha = 0.337). CONCLUSIONS: YouTube videos on small
      pupil phacoemulsification have low complication rates when compared to the
      literature, although no reliable mechanical dilatation methods are used in almost
      half of these videos. Until YouTube's place in e-learning becomes clearer, we
      suggest that viewers be cautious regarding small pupil phacoemulsification videos
      on YouTube.

PMID- 29356981
TI  - Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice
      hippocampus.
AB  - Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might
      be associated with exposure to stress and altered living conditions. This study
      aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in
      improving the neurodegenerative-like changes induced in mice after exposed to
      chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided
      into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were
      used. Behavioral tests, serum corticosterone level, hippocampus protein level of
      the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF)
      were determined after exposure to CUMS. Hippocampus was histopathologically
      examined. Data were analyzed using statistical package for the social sciences
      (SPSS) and P value of less than 0.05 was considered significant. OB diminished
      the depression manifestation as well as impaired short term memory observed in
      the mice after exposure to the CUMS as evidenced by the forced swimming and
      elevated plus maze test. OB also up-regulated the serum corticosterone level,
      hippocampal protein level of the glucocorticoid receptor and the brain-derived
      neurotropic factor and reduced the neurodegenerative and atrophic changes induced
      in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the
      memory impairment and hippocampal neurodegenerative changes induced by exposure
      to the chronic unpredictable stress indicating that it is the time to test its
      effectiveness on patients suffering from Alzheimer disease.

PMID- 29356983
TI  - Assessment of target-mediated uptake with immuno-PET: analysis of a phase I
      clinical trial with an anti-CD44 antibody.
AB  - BACKGROUND: Ideally, monoclonal antibodies provide selective treatment by
      targeting the tumour, without affecting normal tissues. Therefore, antibody
      imaging is of interest, preferably in early stages of drug development. However,
      the imaging signal consists of specific, as well as non-specific, uptake. The aim
      of this study was to assess specific, target-mediated uptake in normal tissues,
      with immuno-PET in a phase I dose escalation study, using the anti-CD44 antibody
      RG7356 as example. RESULTS: Data from thirteen patients with CD44-expressing
      solid tumours included in an imaging sub-study of a phase I dose escalation
      clinical trial using the anti-CD44 antibody RG7356 was analysed. 89Zirconium
      labelled RG7356 (1 mg; 37 MBq) was administered after a variable dose of
      unlabelled RG7356 (0 to 675 mg). Tracer uptake in normal tissues (liver, spleen,
      kidney, lung, bone marrow, brain and blood pool) was used to calculate the area
      under the time antibody concentration curve (AUC) and expressed as tissue-to
      blood AUC ratios. Within the dose range of 1 to 450 mg, tissue-to-blood AUC
      ratios decreased from 10.6 to 0.75 +/- 0.16 for the spleen, 7.5 to 0.86 +/- 0.18
      for the liver, 3.6 to 0.48 +/- 0.13 for the bone marrow, 0.69 to 0.26 +/- 0.1 for
      the lung and 1.29 to 0.56 +/- 0.14 for the kidney, indicating dose-dependent
      uptake. In all patients receiving >= 450 mg (n = 7), tumour uptake of the
      antibody was observed. CONCLUSIONS: This study demonstrates how immuno-PET in a
      dose escalation study provides a non-invasive technique to quantify dose
      dependent uptake in normal tissues, indicating specific, target-mediated uptake.

PMID- 29356984
TI  - Minimally invasive percutaneous endoscopic treatment for acute pyogenic
      spondylodiscitis following vertebroplasty.
AB  - INTRODUCTION: Acute pyogenic spondylodiscitis caused by percutaneous
      vertebroplasty is a rare complication. We present the first report of minimally
      invasive endoscopic treatment for acute spondylodiscitis caused by
      vertebroplasty. CASE PRESENTATION: A 60-year-old female was transferred with the
      symptom of right hip flexion weakness for 1 day. The patient underwent a
      vertebroplasty procedure because of L3 osteoporotic compression fracture at other
      hospital 6 weeks ago. Physical examination, laboratory finding and magnetic
      resonance imaging revealed an acute pyogenic spondylodiscitis with right L2 nerve
      root palsy caused by compression of bone and cement after L3 body collapse.
      Percutaneous endoscopic procedures including needle biopsy, debridement, root
      decompression and drainage were performed. One week after endoscopic treatment,
      her symptoms of back pain and nerve palsy improved significantly. After
      endoscopic treatment, the patient underwent conservative treatment with
      appropriate antibiotics according to the bacterial culture test results. Six
      weeks postoperatively, she was pain free with no neurological deficits or signs
      of infection. Five months later, spontaneous fusion between L2 and L3 body was
      observed. CONCLUSION: We report a case treated with endoscopic procedure without
      open surgery for acute pyogenic spondylodiscitis following vertebroplasty.

PMID- 29356985
TI  - Neoadjuvant denosumab for the treatment of a sacral osteoblastoma.
AB  - PURPOSE: To present a case of aggressive sacral osteoblastoma (OB) treated with
      neoadjuvant denosumab therapy and en bloc resection. METHODS: Case report of a 14
      year-old male with an aggressive OB affecting the superior articular process of
      the left first sacral segment. The lesion was lytic and metabolically active and
      involved the left-sided posterior elements of S1-S3 with extension into the
      spinal canal, affecting the left S1, S2, S3, S4 and S5 nerve roots. He was
      treated for 1 month with neoadjuvant denosumab followed by en bloc resection.
      RESULTS: Denosumab therapy caused regression of the tumour and converted the
      diffuse infiltrative mass into a well-defined solid (osteoma-like) structure,
      aiding surgical resection and preserving the S1, S4 and S5 nerve roots.
      Histologically, the treated lesion showed abundant sclerotic woven bone and
      osteoblasts with absence of osteoclasts. CONCLUSIONS: A short course of denosumab
      caused tumour regression, ossification and conversion of an aggressive OB into a
      sclerotic, well-defined lesion thus aiding surgical resection and preservation of
      neural structures. Neoadjuvant therapy reduced osteoclast numbers but PET showed
      that the lesion remained FDG avid post-therapy.

PMID- 29356986
TI  - Bisphosphonate therapy for spinal aneurysmal bone cysts.
AB  - PURPOSE: To assess the efficacy of bisphosphonate therapy in the management of
      spinal aneurysmal bone cysts (ABCs). METHODS: A prospective study of six
      consecutive patients aged between 7 and 22 years with spinal ABCs treated with
      pamidronate (1 mg/kg) or zoledronate (4 mg). A visual analogue scale (VAS) for
      pain and radiological (contrast-enhanced MRI and CT scan at 3 and 6 months, then
      yearly X-rays) follow-up was continued for a minimum of 6 years. RESULTS: One
      patient with an unstable C2/3 failed to respond to a single dose of
      bisphosphonate and required surgical resection and stabilisation with autologous
      bone grafting. Another, with a thoraco-lumbar ABC, experienced progression of
      neurological dysfunction after one cycle of bisphosphonate and, therefore,
      required surgical resection and stabilisation. In all other patients pain
      progressively improved and was resolved after two to four cycles (VAS 7.3-0).
      These patients all showed reduction in peri-lesional oedema and increased
      ossification by 3 months. No patients have had a recurrence within the timeframe
      of this study. CONCLUSIONS: Bisphosphonate therapy can be used as the definitive
      treatment of spinal ABCs, except in patients with instability or progressive
      neurology, where surgical intervention is required. Clinicians should expect a
      patients symptoms to rapidly improve, their bone oedema to resolve by 3 months
      and their lesion to partially or completely ossify by 6-12 months.

PMID- 29356987
TI  - The influence of cellular senescence on intracellular vitamin C transport,
      accumulation, and function.
AB  - In humans, vitamin C (VC) accumulates at higher concentrations in cells than in
      plasma, and this intracellular accumulation appears critical to several important
      physiological functions. However, although VC accumulation decreases in the
      elderly, the influence of cellular senescence on the transport, accumulation, and
      function of VC is poorly understood. In this study, we investigated the effects
      of supplementation with both ascorbic acid (AsA) and dehydroascorbic acid
      (DehAsA) on the uptake and accumulation of VC, AsA, and DehAsA into cells and the
      effect of AsA on the levels of intracellular reactive oxygen species (ROS) in
      human fibroblast TIG-1 cells. We also assessed how that supplementation affected
      senescence-associated changes in intracellular VC transport and accumulation. AsA
      supplementation significantly increased intracellular levels of AsA, DehAsA, and
      total VC (i.e., reduced AsA plus oxidized DehAsA) in senescent cells compared
      with young cells. DehAsA supplementation also significantly increased
      intracellular AsA and total VC levels in senescent cells, but not DehAsA, and the
      increases were less than after adding AsA. Among the molecules related to VC
      accumulation, the mRNA and protein expressions of sodium-dependent VC transporter
      2 (SLC23A2) were increased in senescent cells. Furthermore, intracellular
      peroxide and superoxide anion levels were higher in senescent cells, with AsA
      supplementation markedly attenuating spontaneous intracellular peroxide
      accumulation. Overall, our results therefore suggest that VC transport and
      accumulation improved in senescent human fibroblast TIG-1 cells due to the
      adaptive upregulation of sodium-dependent VC transporter 2 in response to
      increased ROS levels. We conclude that adequate supplementation with AsA can
      effectively mitigate senescence-associated intracellular ROS.

PMID- 29356988
TI  - The biological changes of umbilical cord mesenchymal stem cells in inflammatory
      environment induced by different cytokines.
AB  - Mesenchymal stem cells (MSCs) are used as therapeutic tool for the treatment of
      immune diseases. The inflammatory environment also influences the characteristics
      of MSCs after transplantation. The aim of the study was to investigate the
      effects of pro-inflammatory cytokines on the characteristics of umbilical cord
      mesenchymal stem cells (UCMSCs). UCMSCs were exposed to pro-inflammatory
      cytokines in vitro for 3 and 7 days, and the biological properties were analyzed.
      The results showed that the proliferation ability was suppressed by interferon
      gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta
      (IL-1beta). The adipogenic capacity was inhibited in all conditioned medium,
      while the chondrogenic and osteogenic capacity was enhanced by TNF-alpha and IL
      1beta in vitro. Prostaglandin E2 (PGE2) was increased by IL-1beta on the third
      day, and angiopoietin-1 (Ang-1) was inhibited appreciably by TNF-alpha on the
      seventh day. Interleukin-6 (IL-6) was increased by TNF-alpha and IL-1beta, and
      hepatocyte growth factor (HGF) was inhibited by all inflammatory cytokines. IFN
      gamma secretion level from human peripheral mononuclear cells (hPBMCs) was
      lowered by UCMSCs which had been stimulated by TNF-alpha or IL-1beta for 3 days.
      Moreover, IFN-gamma and TNF-alpha secretion level was only inhibited by UCMSCs
      which had been by stimulated IFN-gamma for 3 days but not 7 days. Our data
      demonstrated that different inflammatory cytokines and the duration of treatment
      had different effects on the properties of UCMSCs, which might be instructive for
      clinical pretreatment in cellular therapeutics.

PMID- 29356989
TI  - Eplerenone pretreatment protects the myocardium against ischaemia/reperfusion
      injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway in
      diabetic rats.
AB  - We investigated the eplerenone-induced, PI3K/Akt- and GSK-3beta-mediated
      cardioprotection against ischemia/reperfusion (I/R) injury in diabetic rats. The
      study groups comprising diabetic rats were treated for 14 days with 150 mg/kg/day
      eplerenone orally and 1 mg/kg wortmannin (PI3K/Akt antagonist) intraperitoneally
      with eplerenone. On the 15th day, the rats were exposed to I/R injury by 20-min
      occlusion of the left anterior descending coronary artery followed by 30 min of
      reperfusion. The hearts were processed for biochemical, molecular, and
      histological investigations. The I/R injury in diabetic rats inflicted a
      significant rise in the oxidative stress and apoptosis along with a decrease in
      the arterial and ventricular function and the expressions of PI3K/Akt and GSK
      3beta proteins. Eplerenone pretreatment reduced the arterial pressure, cardiac
      inotropy, and lusitropy. It significantly reduced apoptosis and cardiac injury
      markers. The histology revealed cardioprotection in eplerenone-treated rats.
      Eplerenone up-regulated the PI3K/Akt and reduced the GSK-3beta expression. The
      group receiving wortmannin with eplerenone was deprived eplerenone-induced
      cardioprotection. Our results reveal the eplerenone-induced cardioprotection
      against I/R injury in diabetic rats and substantiate the involvement of PI3K/Akt
      and GSK-3beta pathways in its efficacy.

PMID- 29356991
TI  - Detection and analysis of mycovirus-related RNA viruses from grape powdery mildew
      fungus Erysiphe necator.
AB  - The fungus, Erysiphe necator Schw., is an important plant pathogen causing
      powdery mildew disease in grapevines worldwide. In this study, high-throughput
      sequencing of double-stranded RNA extracted from the fungal tissue combined with
      bioinformatics was used to examine mycovirus-related sequences associated with E.
      necator. The results showed the presence of eight mycovirus-related sequences.
      Five of these sequences representing three new mycoviruses showed alignment with
      sequences of viruses classified in the genus Alphapartitivirus in the family
      Partitiviridae. Another three sequences representing three new mycoviruses showed
      similarity to classifiable members of the genus Mitovirus in the family
      Narnaviridae. These mycovirus isolates were named Erysiphe necator partitivirus
      1, 2, and 3 (EnPV 1-3) and Erysiphe necator mitovirus 1, 2, and 3 (EnMV 1-3)
      reflecting their E. necator origin and their phylogenetic affiliation with other
      mycoviruses.

PMID- 29356992
TI  - Identification and production of mouse scFv to specific epitope of enterovirus-71
      virion protein-2 (VP2).
AB  - Enterovirus-71 (EV71) and coxsackievirus-A16 (CA16) frequently cause hand-foot
      mouth disease (HFMD) epidemics among infants and young children. CA16 infections
      are usually mild, while EV71 disease may be fatal due to neurologic
      complications. As such, the ability to rapidly and specifically recognize EV71 is
      needed to facilitate proper case management and epidemic control. Accordingly,
      the aim of this study was to generate antibodies to EV71-virion protein-2 (VP2)
      by phage display technology for further use in specific detection of EV71. A
      recombinant peptide sequence of EV71-VP2, carrying a predicted conserved B cell
      epitope fused to glutathione-S-transferase (GST) (designated GST-EV71-VP2/131
      160), was produced. The fusion protein was used as bait in in-solution biopanning
      to separate protein-bound phages from a murine scFv (MuscFv) phage display
      library constructed from an immunoglobulin gene repertoire from naive ICR mice.
      Three phage-transformed E. coli clones (clones 63, 82, and 83) produced MuscFvs
      that bound to the GST-EV71-VP2/131-160 peptide. The MuscFv of clone 83
      (MuscFv83), which produced the highest ELISA signal to the target antigen, was
      further tested. MuscFv83 also bound to full-length EV71-VP2 and EV71 particles,
      but did not bind to GST, full-length EV71-VP1, or the antigenically related CA16.
      MuscFv83 could be a suitable reagent for rapid antigen-based immunoassay, such as
      immunochromatography (ICT), for the specific detection and/or diagnosis of EV71
      infection as well as epidemic surveillance.

PMID- 29356990
TI  - Taxonomy of prokaryotic viruses: 2017 update from the ICTV Bacterial and Archaeal
      Viruses Subcommittee.

PMID- 29356993
TI  - Phantom and clinical evaluation of the effect of full Monte Carlo collimator
      modelling in post-SIRT yttrium-90 Bremsstrahlung SPECT imaging.
AB  - BACKGROUND: Post-therapy SPECT/CT imaging of 90Y microspheres delivered to
      hepatic malignancies is difficult, owing to the continuous, high-energy
      Bremsstrahlung spectrum emitted by 90Y. This study aimed to evaluate the utility
      of a commercially available software package (HybridRecon, Hermes Medical
      Solutions AB) which incorporates full Monte Carlo collimator modelling. Analysis
      of image quality was performed on both phantom and clinical images in order to
      ultimately provide a recommendation of an optimum reconstruction for post-therapy
      90Y microsphere SPECT/CT imaging. A 3D-printed anthropomorphic liver phantom was
      filled with 90Y with a sphere-to-background ratio of 4:1 and imaged on a GE
      Discovery 670 SPECT/CT camera. Datasets were reconstructed using ordered-subsets
      expectation maximization (OSEM) 1-7 iterations in order to identify the optimal
      OSEM reconstruction (5 iterations, 15 subsets). Quantitative analysis was
      subsequently carried out on phantom datasets obtained using four reconstruction
      algorithms: the default OSEM protocol (2 iterations, 10 subsets) and the
      optimised OSEM protocol, both with and without full Monte Carlo collimator
      modelling. The quantitative metrics contrast recovery (CR) and background
      variability (BV) were calculated. The four algorithms were then used to
      retrospectively reconstruct 10 selective internal radiation therapy (SIRT)
      patient datasets which were subsequently blind scored for image quality by a
      consultant radiologist. RESULTS: The optimised OSEM reconstruction (5 iterations,
      15 subsets with full MC collimator modelling) increased the CR by 42% (p < 0.001)
      compared to the default OSEM protocol (2 iterations, 10 subsets). The use of full
      Monte Carlo collimator modelling was shown to further improve CR by 14% (30 mm
      sphere, CR = 90%, p < 0.05). The consultant radiologist had a significant
      preference for the optimised OSEM over the default OSEM protocol (p < 0.001),
      with the optimised OSEM being the favoured reconstruction in every one of the 10
      clinical cases presented. CONCLUSIONS: OSEM (5 iterations, 15 subsets) with full
      Monte Carlo collimator modelling is quantitatively the optimal image
      reconstruction for post-SIRT 90Y Bremsstrahlung SPECT/CT imaging. The use of full
      Monte Carlo collimator modelling for correction of image-degrading effects
      significantly increases contrast recovery without degrading clinical image
      quality.

PMID- 29356994
TI  - Mutations in SUFU and PTCH1 genes may cause different cutaneous cancer
      predisposition syndromes: similar, but not the same.
AB  - Many cancer predisposition syndromes are preceded or accompanied by a range of
      typical skin signs. Gorlin syndrome is a rare multisystem inherited disorder
      which can predispose to basal cell carcinomas (BCCs), childhood medulloblastomas
      in addition to various developmental abnormalities; the majority of cases are due
      to mutations in the PTCH1 gene. Approximately 5% of cases have been attributed to
      a mutation in the SUFU gene. Certain phenotypic features have been identified as
      being more prevalent in individuals with a SUFU mutation such as childhood
      medulloblastoma, infundibulocystic BCCs and trichoepitheliomas. Recently
      hamartomatous skin lesions have also been noted in families with childhood
      medulloblastoma, a "Gorlin like" phenotype and a SUFU mutation. Here we describe
      a family previously diagnosed with Gorlin syndrome with a novel SUFU splice site
      deleterious genetic variant, who have several dermatological features including
      palmar sclerotic fibromas which has not been described in relation to a SUFU
      mutation before. We highlight the features more prominent in individuals with a
      SUFU mutation. It is important to note that emerging therapies for treatment of
      BCCs in patients with a PTCH1 mutation may not be effective in those with a SUFU
      mutation.

PMID- 29356995
TI  - Effect of qGN4.1 QTL for Grain Number per Panicle in Genetic Backgrounds of
      Twelve Different Mega Varieties of Rice.
AB  - BACKGROUND: Rice is a major source of food, particularly for the growing Asian
      population; hence, the utilization of genes for enhancing its yield potential is
      important for ensuring food security. Earlier, we have mapped a major
      quantitative trait loci (QTL) for the grain number per panicle, qGN4.1, using
      biparental recombinant inbred line (RIL) populations involving a new plant type
      Indica rice genotype Pusa 1266. Later, three independent studies have confirmed
      the presence of a major QTL for spikelet number by three different names (SPIKE,
      GPS and LSCHL4) in the same chromosomal region, and have implicated the
      overexpression of Nal1 gene as the causal factor for high spikelet number.
      However, the effect of qGN4.1 in different rice genetic backgrounds and
      expression levels of the underlying candidate genes is not known. RESULTS: Here,
      we report the effect of qGN4.1 QTL in the genetic backgrounds of 12 different
      high-yielding mega varieties of rice, introgressed by marker assisted-backcross
      breeding (MABB) using two QTL positive markers for foreground selection and two
      QTL negative flanking markers for recombinant selection together with phenotypic
      selection for the recovery of recipient parent genetic background. Analysis of
      the performance of BC2F3 plants showed a significant increase in the average
      number of well-filled grains per panicle in all the backgrounds, ranging from
      21.6 in CSR 30-GN4.1 to 147.6 in Samba Mahsuri-GN4.1. Furthermore, qGN4.1 caused
      a significant increase in flag leaf width and panicle branching in most
      backgrounds. We identified BC3F3 qGN4.1 near-isogenic lines (NILs) with 92.0
      98.0% similarity to the respective recipient parent by background analysis using
      a 50 K rice SNP genotyping chip. Three of the NILs, namely Pusa Basmati 1121
      GN4.1, Samba Mahsuri-GN4.1 and Swarna-GN4.1, showed a significant yield
      superiority to their recipient parents. Analysis of differential gene expression
      revealed that high grain number in these QTL-NILs was unlikely due to the
      overexpression of Nal1 gene (LOC_Os04g52479). Instead, another tightly linked
      gene (LOC_Os04g52590) coding for a protein kinase domain-containing protein was
      consistently overexpressed in the high grain number NILs. CONCLUSION: We have
      successfully introgressed the qGN4.1 QTL for high grain number per panicle into
      12 different mega varieties of rice using marker-assisted backcross breeding. The
      advanced near-isogenic lines are promising for the development of even higher
      yielding versions of these high-yielding mega varieties of rice.

PMID- 29356996
TI  - The Application of Pulsed Electromagnetic Fields (PEMFs) for Bone Fracture
      Repair: Past and Perspective Findings.
AB  - Bone fractures are one of the most commonly occurring injuries of the
      musculoskeletal system. A highly complex physiological process, fracture healing
      has been studied extensively. Data from in vivo, in vitro and clinical studies,
      have shown pulsed electromagnetic fields (PEMFs) to be highly influential in the
      fracture repair process. Whilst the underlying mechanisms acting to either
      inhibit or advance the physiological processes are yet to be defined
      conclusively, several non-invasive point of use devices have been developed for
      the clinical treatment of fractures. With the complexity of the repair process,
      involving many components acting at different time steps, it has been a challenge
      to determine which PEMF exposure parameters (i.e., frequency of field, intensity
      of field and dose) will produce the most optimal repair. In addition, the
      development of an evidence-backed device comes with challenges of its own, with
      many elements (including process of exposure, construct materials and tissue
      densities) being highly influential to the field exposed. The objective of this
      review is to provide a broad recount of the applications of PEMFs in bone
      fracture repair and to then demonstrate what is further required for enhanced
      therapeutic outcomes.

PMID- 29356997
TI  - Hydroxyapatite Crystal Thickness and Buckling Phenomenon in Bone Nanostructure
      During Mechanical Tests.
AB  - An investigation of bone samples taken from the left ulna of New Zealand white
      rabbits, with and without stresses and hysteresis loop, was undertaken using
      Small Angle X-ray Scattering technique. The purpose of this study is to
      investigate the nanostructural changes in the mean size of hydroxyapatite
      crystals thickness (T) during different mechanical conditions. The experiments
      were performed using bone samples aged 2 and 4 weeks, with and without strontium
      ranelate treatment, after compressive load and hysteresis loop. We did not
      observe any clear effects of strontium ranelate on the bones since the MANOVA
      test for epiphysis and diaphysis were found. On the other hand, a significant
      difference appears in epiphysis between 2 and 4 weeks. Furthermore, a reduction
      in the mean size of hydroxyapatite crystal thickness was observed when the
      loading pressure force increased, due to the buckling phenomenon. A return of
      memory points in the elastic region of the bone was observed. The significance of
      these results lays on the development of nanoproducts, with properties that are
      closer to the actual bone structure.

PMID- 29356998
TI  - Real-Time Closed Loop Diastolic Interval Control Prevents Cardiac Alternans in
      Isolated Whole Rabbit Hearts.
AB  - Cardiac alternans, a beat-to-beat alternation in action potential duration (APD),
      can lead to fatal arrhythmias. During periodic pacing, changes in diastolic
      interval (DI) depend on subsequent changes in APD, thus enhancing cardiac
      instabilities through a 'feedback' mechanism. Recently, an anti-arrhythmic
      Constant DI pacing protocol was proposed and shown to be effective in suppressing
      alternans in 0D and 1D in silico studies. However, previous experimental
      validation of Constant DI pacing in the heart has been unsuccessful due to the
      spatio-temporal complexity of 2D cardiac tissue and the technical challenges in
      its real-time implementation. Here, we developed a novel closed loop system to
      detect T-waves from real-time ECG data, enabling successful implementation of
      Constant DI pacing protocol, and performed high-resolution optical mapping
      experiments on isolated whole rabbit hearts to validate its anti-arrhythmic
      effects. The results were compared with: (1) Periodic pacing (feedback inherent)
      and (2) pacing with heart rate variability (HRV) (feedback modulation) introduced
      by using either Gaussian or Physiological patterns. We observed that Constant DI
      pacing significantly suppressed alternans in the heart, while maintaining APD
      spatial dispersion and flattening the slope of the APD restitution curve,
      compared to traditional Periodic pacing. In addition, introduction of HRV in
      Periodic pacing failed to prevent cardiac alternans, and was arrhythmogenic.

PMID- 29356999
TI  - [Urethral strictures : From diagnostic workup to appropriate and situation
      dependent treatment].

PMID- 29357000
TI  - [Editorial].

PMID- 29357007
TI  - Oral prednisolone versus non-steroidal anti-inflammatory drugs in the treatment
      of acute gout: a meta-analysis of randomized controlled trials.
AB  - OBJECTIVES: To evaluate the efficacy and safety of oral prednisolone in the
      treatment of acute gout compared with non-steroidal anti-inflammatory drugs
      (NSAIDs). METHODS: A comprehensive search of databases in both Chinese and
      English was performed. Data from the selected studies were extracted and analyzed
      independently by two authors. RESULTS: Three double-blind, randomized, controlled
      trials were included in the final analysis, with a total of 584 patients.
      Regarding the efficacy, oral prednisolone (30-35 mg/day) was comparable with
      NSAIDs (naproxen at 500 mg/day or indomethacin at 50-100 mg/day) on the pain
      relief scale, both in activity (difference in means 0.259, 95% CI - 1.532 to
      2.050, P = 0.777) and at rest (difference in means - 0.502, 95% CI - 4.961 to
      3.956, P = 0.825) during the first 2-6 h. During the following 4 to 6 days,
      prednisolone acted with comparable efficacy either in activity (difference in
      means - 0.552, 95% CI - 1.364 to 0.260, P = 0.183) or at rest (difference in
      means - 0.164, 95% CI - 0.463 to 0.134, P = 0.281). Regarding safety,
      prednisolone did not increase the total adverse events (AEs) (risk ratios [RR]
      0.765, 95% CI 0.473 to 1.238, P = 0.275) and reduced the withdrawal rate because
      of the AEs (RR 0.127, 95% CI 0.021-0.763, P = 0.024). Prednisolone decreased the
      risks of several AEs (including indigestion: RR 0.544, 95% CI 0.311-0.952, P =
      0.033; nausea: RR 0.296, 95% CI 0.136-0.647, P = 0.002; and vomiting: RR 0.155,
      95% CI 0.033-0.722, P = 0.018) but increased the risk of skin rashes (RR 4.049,
      95% CI 1.241-13.158, P = 0.021). CONCLUSIONS: Oral prednisolone may be of similar
      efficacy and a slightly safer strategy for treatment of active, acute gout
      compared with NSAIDs. Further clinical studies are still warranted to investigate
      its long-term efficacy and safety.

PMID- 29357008
TI  - Matricellular CCN6 (WISP3) protein: a tumor suppressor for mammary metaplastic
      carcinomas.
AB  - Located at 6q22-23, Ccn6 (WISP3) encodes for a matrix-associated protein of the
      CCN family, characterized by regulatory, rather than structural, roles in
      development and cancer. CCN6, the least studied member of the CCN family, shares
      the conserved multimodular structure of CCN proteins, as well as their tissue and
      cell-type specific functions. In the breast, CCN6 is a critical regulator of
      epithelial-to-mesenchymal transitions (EMT) and tumor initiating cells. Studies
      using human breast cancer tissue samples demonstrated that CCN6 messenger RNA and
      protein are expressed in normal breast epithelia but reduced or lost in
      aggressive breast cancer phenotypes, especially inflammatory breast cancer and
      metaplastic carcinomas. Metaplastic carcinomas are mesenchymal-like triple
      negative breast carcinomas, enriched for markers of EMT and stemness. RNAseq
      analyses of the TCGA Breast Cancer cohort show reduced CCN6 expression in
      approximately 50% of metaplastic carcinomas compared to normal breast. Our group
      identified frameshift mutations of Ccn6 in a subset of human metaplastic breast
      carcinoma. Importantly, conditional, mammary epithelial-cell specific ccn6
      (wisp3) knockout mice develop invasive high-grade mammary carcinomas that
      recapitulate human spindle cell metaplastic carcinomas, demonstrating a tumor
      suppressor function for ccn6. Our studies on CCN6 functions in metaplastic
      carcinoma highlight the potential of CCN6 as a novel therapeutic approach for
      this specific type of breast cancer.

PMID- 29357009
TI  - The matricellular protein CCN1 in tissue injury repair.
AB  - The expression of Ccn1 (Cyr61) is essential for cardiovascular development during
      embryogenesis, whereas in adulthood it is associated with inflammation, wound
      healing, injury repair, and related pathologies including fibrosis and cancer.
      Recent studies have found that CCN1 plays a critical role in promoting wound
      healing and tissue repair. Mechanistically, CCN1 functions through direct
      interaction with specific integrin receptors expressed in various cell types in
      the wound tissue microenvironment to coordinate diverse cellular functions for
      repair. Here we briefly summarize the current knowledge on the functions of CCN1
      in tissue injury repair and discuss pertinent unanswered questions.

PMID- 29357010
TI  - Lower life satisfaction, active coping and cardiovascular disease risk factors in
      older African Americans: outcomes of a longitudinal church-based intervention.
AB  - This study examined lower life satisfaction, active coping and cardiovascular
      disease risk factors (diastolic and systolic blood pressure, body mass index, and
      circumferences) in older African Americans over the phases of an 18-month church
      based intervention, using a quasi-experimental design. Participants (n = 89) were
      45 years of age and older from six churches (three treatment, three comparison)
      in North Florida. Lower life satisfaction had a persistent unfavorable effect on
      weight variables. Active coping showed a direct beneficial effect on selected
      weight variables. However, active coping was adversely associated with blood
      pressure, and did not moderate the association between lower life satisfaction
      and cardiovascular risk factors. The intervention had a beneficial moderating
      influence on the association between lower life satisfaction and weight variables
      and on the association between active coping and these variables. Yet, this
      pattern did not hold for the association between active coping and blood
      pressure. The relationship of lower life satisfaction and selected cardiovascular
      risk factors and the positive effect of active coping were established, but
      findings regarding blood pressure suggest further study is needed.

PMID- 29357011
TI  - Immunogenomics: A Negative Prostate Cancer Outcome Associated with TcR
      gamma/delta Recombinations.
AB  - We developed a scripted algorithm, based on previous, earlier editions of the
      algorithm, to mine prostate cancer exome files for T-cell receptor (TcR)
      recombination reads: Reads representing TcR gene recombinations were identified
      in 497 prostate cancer exome files from the cancer genome atlas (TCGA). As has
      been reported for melanoma, co-detection of productive TcR-alpha and TcR-beta
      recombination reads correlated with an RNA expression signature representing T
      cell exhaustion, particularly with high RNA levels for PD-1 and PD-L1, in
      comparison to several different control sets of samples. Co-detection of TcR
      alpha and TcR-beta recombination reads also correlated with high level expression
      of genes representing antigen presenting functions, further supporting the
      conclusion that co-detection of TcR-alpha and TcR-beta recombination reads
      represents an immunologically relevant microenvironment. Finally, detection of
      unproductive TcR-delta recombinations, and unproductive and productive TcR-gamma
      recombinations, strongly correlated with, and may represent a convenient
      biomarker for a poor clinical outcome. These results underscore the value of the
      genomics-based assessment of unproductive TcR recombinations and raise questions
      about the impact of tumor microenvironment lymphocytes in the absence of
      antigenicity.

PMID- 29357013
TI  - Validation of the prognostic impact of the new tumor-node-metastasis clinical
      staging in patients with gastric cancer.
AB  - BACKGROUND: In the 8th edition of the tumor-node-metastasis (TNM) classification,
      the gastric cancer staging system includes two classifications: the clinical
      stage (cStage) and the postoperative pathologic stage. However, the correlation
      between the new cStage and overall survival has not been studied. Moreover,
      clinical N (cN) grade analysis is not included in the new clinical staging
      system. This study validated the prognostic value of cStage in the 8th edition of
      the TNM classification and the significance of N classification for pretreatment
      staging in gastric cancer. METHODS: A total of 4374 patients with primary gastric
      cancer who underwent surgery at the Shizuoka Cancer Center were included.
      Survival analysis was conducted based on the newly proposed cStage criteria of
      the TNM 8th edition. Prognostic accuracy was evaluated using Harrell's
      concordance index (C-index). RESULTS: The five-year survival rates according to
      cStage were as follows: cStageI, 91.2%, cStageIIA: 75.1%, cStageIIB: 57.7%,
      cStageIII: 43.2%, cStageIVA: 31.6%, and cStageIVB: 7.7%. Significant differences
      were observed among all stages (P < 0.001). The cStage C-index was 0.802.
      Meanwhile, the five-year survival rates based on cN were as follows: cN0: 83.7%,
      cN1: 57.2%, cN2: 42.4%, cN3a: 22.1%, and cN3b: 0.0%. Significant differences were
      also observed among all cN grades (P < 0.001). CONCLUSIONS: The cStage of the 8th
      edition of the TNM classification has a good capability to predict prognosis;
      thus, it may be a useful indicator for selecting appropriate gastric cancer
      treatment modalities. In addition, cN can be included in developing a more
      precise clinical staging of gastric cancer.

PMID- 29357012
TI  - Efficacy of polyglycolic acid sheets and fibrin glue for prevention of bleeding
      after gastric endoscopic submucosal dissection in patients under continued
      antithrombotic agents.
AB  - BACKGROUND: A novel method for the prevention of bleeding after gastric
      endoscopic submucosal dissection (ESD) is necessary, as the numbers of patients
      taking antithrombotic agents have increased. This study aimed to assess the
      efficacy and safety of the covering method using polyglycolic acid (PGA) sheets
      and fibrin glue for ESD-induced ulcer in preventing post-ESD bleeding in patients
      under continued antithrombotic agents. METHODS: One hundred five consecutive
      gastric tumors among 84 patients who were treated by ESD under continued
      antithrombotic agents between April 2014 and September 2015 were enrolled in this
      study. The patients were classified into two groups, the covering group (52
      lesions among 38 patients; those with ESD in whom PGA sheets and fibrin glue were
      used as the covering method) and the control group (53 lesions among 46 patients;
      ESD only), and their post-ESD bleeding rates were compared. RESULTS: No
      significant differences were seen in the number and type of antithrombotic
      agents, lesion location, median procedure time, and median resected specimen size
      between the groups. ESD was completed in all cases, with no cases of
      uncontrollable bleeding during the procedure. Post-ESD bleeding occurred in 5.8%
      (3/52) and 20.8% (11/53) in the covering and control groups, respectively. The
      post-ESD bleeding rate significantly differed between the groups (P = 0.04; odds
      ratio, 0.23; 95% confidential interval, 0.06-0.89). No adverse events were
      associated with the use of PGA sheets and fibrin glue. CONCLUSIONS: The covering
      method using PGA sheets and fibrin glue has the potential to reduce post-ESD
      bleeding in patients receiving continued antithrombotic agents.

PMID- 29357014
TI  - Ipsilateral Saccade Hypometria and Contralateral Saccadic Pursuit in a Focal
      Brainstem Lesion: a Rare Oculomotor Pattern.
AB  - Eye movement examination may be used to rapidly differentiate peripheral and
      central vestibular syndromes in patients with acute unsteadiness. The analysis of
      oculomotor impairments may also support the accurate localization of cerebral
      lesions, particularly those in the brainstem, that are often loosely defined by
      cerebral MRIs. Saccades, smooth pursuit, and nystagmus were recorded with video
      oculography in a patient who had developed sudden vertigo as a consequence of a
      focal lesion in the depth of the brachium pontis. The patient had shown a
      previously unreported pattern of eye movement impairments consisting of (i)
      ipsilesional hypometric saccades, (ii) contralesional saccadic smooth pursuit,
      and (iii) unilateral gaze-evoked nystagmus. These symptoms enabled the precise
      localization of the trajectory of pontocerebellar saccadic tracts in the depth of
      the brachium pontis. We propose that this rare association resulted from a
      disruption of cerebellar afferents of saccadic pathways and of cerebellar
      efferents of horizontal smooth pursuit pathways. This reported case emphasizes
      the crucial role of careful bedside oculomotor examination in order to
      discriminate between peripheral and central vestibular syndromes in the diagnosis
      of sudden vertigo. Moreover, it reveals an exceptional pattern of oculomotor
      impairments that may allow for the precise localization of the trajectory of
      cerebellar saccadic afferent pathways in the depth of the brachium pontis.

PMID- 29357015
TI  - Influence of principal component analysis acceleration factor on velocity
      measurement in 2D and 4D PC-MRI.
AB  - OBJECTIVE: The objective of the study was to determine how to optimize 2D and 4D
      phase-contrast magnetic resonance imaging (PC-MRI) acquisitions to acquire flow
      velocities in millimetric vessels. In particular, we search for the best
      compromise between acquisition time and accuracy and assess the influence of the
      principal component analysis (PCA). MATERIALS AND METHODS: 2D and 4D PC-MRI
      measurements are conducted within two in vitro vessel phantoms: a Y-bifurcation
      phantom, the branches of which range from 2 to 5 mm in diameter, and a
      physiological subject-specific phantom of the carotid bifurcation. The same
      sequences are applied in vivo in carotid vasculature. RESULTS: For a vessel
      oriented in the axial direction, both 2D and axial 4D PC-MRI provided accuracy
      measurements regardless of the k-t PCA factor, while the acquisition time is
      reduced by a factor 6 for k-t PCA maximum value. The in vivo measurements show
      that the proposed sequences are adequate to acquire 2D and 4D velocity fields in
      millimetric vessels and with clinically realistic time durations. CONCLUSION: The
      study shows the feasibility of conducting fast, high-resolution PC-MRI flow
      measurements in millimetric vessels and that it is worth maximizing the k-t PCA
      factor to reduce the acquisition time in the case of 2D and 4D axial
      acquisitions.

PMID- 29357016
TI  - New Developments in the Diagnosis, Therapy, and Monitoring of Eosinophilic
      Esophagitis.
AB  - PURPOSE OF REVIEW: Eosinophilic esophagitis (EoE) has transformed over the past
      two decades from a little-known entity to a significant cause of morbidity in the
      adult and pediatric population. We reviewed the most recent advancements in the
      diagnosis, therapy, and long-term monitoring of EoE. RECENT FINDINGS: Based on
      clinical, endoscopic, histologic, immunologic, and genetic similarities, there is
      growing consensus to move away from distinguishing proton pump inhibitor
      responsive esophageal eosinophilia as an entity distinct from EoE. An increasing
      number of studies have identified duration of untreated disease as an important
      determinant of esophageal stricture formation. New approaches to the empiric
      elimination diet including one, two, four, and step-up protocols were developed
      to reduce the need for repeated endoscopies during reintroduction of food
      triggers. Topical steroids remain the mainstay of medical therapy but newer
      formulations are under development to optimize esophageal delivery. Novel,
      disease activity monitoring techniques are being evaluated that assess esophageal
      inflammatory activity without the need for endoscopy. Understanding of EoE has
      increased remarkably from the first identification of the disease. The underlying
      pathogenesis continues to be explored leading to shifts in diagnostic criteria as
      well as novel therapeutic targets. Innovative methods to monitor disease are
      under investigation and more research is needed to understand the natural history
      of EoE.

PMID- 29357018
TI  - Glutamate Dehydrogenase as a Neuroprotective Target Against Neurodegeneration.
AB  - Regulation of glutamate metabolism via glutamate dehydrogenase (GDH) might be the
      promising therapeutic approach for treating neurodegenerative disorders. In the
      central nervous system, glutamate functions both as a major excitatory
      neurotransmitter and as a key intermediate metabolite for neurons. GDH converts
      glutamate to alpha-ketoglutarate, which serves as a TCA cycle intermediate.
      Dysregulated GDH activity in the central nervous system is highly correlated with
      neurological disorders. Indeed, studies conducted with mutant mice and allosteric
      drugs have shown that deficient or overexpressed GDH activity in the brain can
      regulate whole body energy metabolism and affect early onset of Parkinson's
      disease, Alzheimer's disease, temporal lobe epilepsy, and spinocerebellar
      atrophy. Moreover, in strokes with excitotoxicity as the main pathophysiology,
      mice that overexpressed GDH exhibited smaller ischemic lesion than mice with
      normal GDH expression. In additions, GDH activators improve lesions in vivo by
      increasing alpha-ketoglutarate levels. In neurons exposed to an insult in vitro,
      enhanced GDH activity increases ATP levels. Thus, in an energy crisis, neuronal
      mitochondrial activity is improved and excitotoxic risk is reduced. Consequently,
      modulating GDH activity in energy-depleted conditions could be a sound strategy
      for maintaining the mitochondrial factory in neurons, and thus, protect against
      metabolic failure.

PMID- 29357017
TI  - Berberine Ameliorates MCAO Induced Cerebral Ischemia/Reperfusion Injury via
      Activation of the BDNF-TrkB-PI3K/Akt Signaling Pathway.
AB  - Cerebral ischemic injury remains associated with high mortality rates and lacks
      effective therapeutic intervention. Berberine (BBR) possesses anti-oxidant, anti
      inflammatory, and anti-tumor activities, as well as potent neuroprotective
      effects. Although recent studies have examined the neuroprotective effects of
      berberine, little is known regarding its usefulness in treating cerebral
      ischemia. Thus, the aim of this study is to investigate the possible effect and
      the mechanism of berberine against cerebral ischemic injury using the middle
      cerebral artery occlusion (MCAO) model. Rats were randomly divided into three
      groups: control group, MCAO group, and MCAO + BBR group. Modified neurological
      severity score tests (mNSS) and infarct volumes were measured to determine the
      neuroprotective effects of berberine. Neuronal survival in striatum was examined
      by TUNEL staining and immunohistochemistry. Western blotting measured the
      expression of BDNF, TrkB, p-Akt and cleaved caspase-3. The results demonstrated
      that BBR could significantly protect against MCAO. Berberine also increased the
      expression of BDNF, TrkB, and p-Akt, which were reduced after MCAO. Furthermore,
      treatment with BBR declined the apoptosis-related proteins induced by MCAO.
      However, treatment with LY294002 (PI3K inhibitor) reversed the BBR-induced
      increases in BDNF and p-Akt proteins and decreased cleaved caspase-3 protein
      expression in focal cerebral ischemic rats. In summary, our results demonstrated
      that BBR could exert neuroprotective effects through reduction of striatum
      apoptosis via the BDNF-TrkB-PI3K/Akt signaling pathway.

PMID- 29357019
TI  - Disruption to the 5-HT7 Receptor Following Hypoxia-Ischemia in the Immature
      Rodent Brain.
AB  - It has become increasingly evident the serotonergic (5-hydroxytryptamine, 5-HT)
      system is an important central neuronal network disrupted following neonatal
      hypoxic-ischemic (HI) insults. Serotonin acts via a variety of receptor subtypes
      that are differentially associated with behavioural and cognitive mechanisms. The
      5-HT7 receptor is purported to play a key role in epilepsy, anxiety, learning and
      memory and neuropsychiatric disorders. Furthermore, the 5-HT7 receptor is highly
      localized in brain regions damaged following neonatal HI insults. Utilising our
      well-established neonatal HI model in the postnatal day 3 (P3) rat pup we
      demonstrated a significant decrease in levels of the 5-HT7 protein in the frontal
      cortex, thalamus and brainstem one week after insult. We also observed a relative
      decrease in both the cytosolic and membrane fractions of 5-HT7. The 5-HT7
      receptor was detected on neurons throughout the cortex and thalamus, and 5-HT
      cell bodies in the brainstem. However we found no evidence of 5-HT7 co
      localisation on microglia or astrocytes. Moreover, minocycline treatment did not
      significantly prevent the HI-induced reductions in 5-HT7. In conclusion, neonatal
      HI injury caused significant disruption to 5-HT7 receptors in the forebrain and
      brainstem. Yet the use of minocycline to inhibit activated microglia, did not
      prevent the HI-induced changes in 5-HT7 expression.

PMID- 29357020
TI  - Evaluating the Effectiveness of an Integrated Cognitive-Behavioural Intervention
      (CBI) Model for Male Problem Gamblers in Hong Kong: A Matched-Pair Comparison
      Design.
AB  - Very few clinical cognitive-behavioural intervention (CBI) studies were conducted
      with the Chinese gamblers. There is a lack of attention paid to intervening in
      negative emotions that may also adversely affect PGs in current CBI treatment
      modality. This study is the first attempt to systematically and rigorously
      evaluate both the short-term and longer-term effects of a culturally-attuned CBI
      group treatment with an emotion regulation component for a group of Chinese PGs
      in Hong Kong. A quasi-experimental matched-pairs design was adopted and 84
      participants were allocated to the CBI (N = 42) and social activity groups (N =
      42). There are 3 assessment points in the study: baseline at recruitment, post
      intervention at the end of CBI and social activity groups, and at 6-month follow
      up. When compared to the social activity group and after controlling for general
      group effects, there were significantly greater decreases in the severity of
      gambling, gambling-related cognitions (i.e. interpretive bias), negative
      psychological states (i.e. stress) and money spent on gambling in the past month
      in the CBI group between pre- and post-intervention and between pre-intervention
      and 6-month follow-up. Results also indicated that both reduction in gambling
      related cognitions and negative psychological states could mediate the treatment
      effect of the CBI on the reduction of problematic gambling behaviours. The
      culturally attuned integrated CBI group treatment with an emotional regulation
      component appeared to be effective in treating Chinese problem gamblers in Hong
      Kong and the effects could be sustained at 6-month follow-up.

PMID- 29357021
TI  - Candidate molecular pathways of white matter vulnerability in the brain of normal
      aging rhesus monkeys.
AB  - Mammalian aging is associated with decline in cognitive functions. Studies
      searching for a cause of cognitive aging initially focused on neuronal loss but
      quantitative investigations of rat, monkey, and human brain using stereology
      demonstrated that in normal aging, unlike in neurodegenerative disease, neurons
      are not lost. Instead, electron microscopic and MRI studies in normal aging
      monkeys revealed age-related damage to myelin sheaths, loss of axons, and
      reduction in white matter volume which correlates with cognitive impairments.
      However, little is known about the cause of myelin defects or associated axon
      loss. The present study investigates the effect of age on signaling pathways
      between oligodendroglia and neurons using a custom PCR array to assess the
      expression of 87 genes of interest in cortical gray matter and white matter from
      the inferior parietal lobe (IPL) of normal rhesus monkeys ranging in age from 4.2
      to 30.4 years old. From this array data, five target genes of interest were
      selected for further analysis to confirm gene expression and measure protein
      expression. The most interesting target gene identified is brain-derived
      neurotrophic factor (BDNF), which was the only gene that was altered at both mRNA
      and protein levels. In gray matter, BDNF mRNA was decreased. While the level of
      the mature form of the protein was unchanged, there was a specific decrease in
      the precursor form of BDNF. These alterations in the BDNF in gray matter could
      contribute to the vulnerability and loss of the axons with age.

PMID- 29357022
TI  - Impact on disease-free survival of the duration of ovarian function suppression,
      as postoperative adjuvant therapy, in premenopausal women with hormone receptor
      positive breast cancer: a retrospective single-institution study.
AB  - INTRODUCTION: Although tamoxifen (TAM) plus ovarian function suppression (OFS) is
      considered as a standard adjuvant treatment for premenopausal women with hormone
      receptor-positive breast cancer, the optimal duration of OFS has not yet been
      established. This retrospective study was designed to assess the duration of OFS
      and the impact of the duration of OFS on the DFS in these patients. METHODS: We
      retrospectively reviewed the data of premenopausal patients with breast cancer
      who received TAM + OFS (goserelin or leuprorelin) as adjuvant therapy between
      February 2004 and June 2015. The primary analysis was a comparison of the disease
      free survival (DFS) between patients who received OFS for 3 years or less (OFS <=
      3 years group) and those who received OFS for longer than 3 years (OFS > 3 years
      group). RESULTS: We analyzed the data of 215 premenopausal patients diagnosed as
      having hormone receptor-positive breast cancer. A propensity score-matched model
      showed the absence of any significant difference in the DFS between the OFS <= 3
      years group and OFS > 3 years group (6-year DFS rate, 93.2 vs. 94.0%; log-rank
      test p = 0.767). CONCLUSIONS: Our data showed that among premenopausal women with
      hormone receptor-positive breast cancer who received TAM + OFS as adjuvant
      endocrine therapy, there was no significant difference in the DFS between the OFS
      <= 3-year group and OFS > 3-year group. A randomized trial is needed to establish
      the optimal duration of OFS for these patients.

PMID- 29357023
TI  - Early prediction of triple negative breast cancer response to cisplatin treatment
      using diffusion-weighted MRI and 18F-FDG-PET.
AB  - BACKGROUND: We evaluated the potential of diffusion-weighted MRI (DW-MRI) and 18F
      FDG-PET for the early prediction of a triple negative breast cancer (TNBC)
      response to cisplatin. METHODS: Cisplatin-treated TNBC tumor-bearing mice were
      categorized as responders or non-responders based on the tumor growth rate. DW
      MRI and 18F-FDG-PET were performed before and after treatment (day 0 and days 3
      and 7, respectively). The average apparent diffusion coefficient value (ADCmean),
      the highest standardized uptake value (SUVmax), and the metabolic tumor volume
      (MTV) were measured. The ratios of each parameter relative to day 0 were
      calculated [DeltaADCmean (day 3) and (day 7), DeltaSUVmax (day 3) and (day 7),
      and DeltaMTV (day 3) and (day 7), respectively]. Overall survival rates were
      compared based on the thresholds determined by these parameters. RESULTS: Both
      the day 3 and day 7 ratios of ADCmean and MTV showed significant differences
      between the responder and non-responder groups, whereas the ratios of SUVmax did
      not. Mice with DeltaADCmean (day 3) exceeding the threshold showed a longer
      overall survival rate. Mice with DeltaSUVmax (day 7), DeltaMTV (day 3), and
      DeltaMTV (day 7) below the respective thresholds showed a longer overall survival
      rate. CONCLUSIONS: The ratios of ADCmean, SUVmax, and MTV have the potential to
      predict the therapeutic response and to screen non-responders in the ultra-early
      phase following cisplatin treatment in patients with TNBC.

PMID- 29357024
TI  - Plant regeneration via direct somatic embryogenesis from leaf explants of
      Tolumnia Louise Elmore 'Elsa'.
AB  - BACKGROUND: Tolumnia genus (equitant Oncidium) is a group of small orchids with
      vivid flower color. Thousands of hybrids have been registered on Royal
      Horticulture Society and showed great potential for ornamental plant market. The
      aim of this study is to establish an efficient method for in vitro propagation.
      RESULTS: Leaf explants taken from in vitro-grown plants were used to induce
      direct somatic embryogenesis on a modified 1/2 MS medium supplemented with five
      kinds of cytokinins, 2iP, BA, kinetin, TDZ and zeatin at 0.3, 1 and 3 mg l-1 in
      darkness. TDZ at 3 mg l-1 gave the highest percentage of explants with somatic
      globular embryos after 90 days of culture. It was found that 2,4-D and light
      regime highly retarded direct somatic embryogenesis and showed 95-100% of explant
      browning. Histological observations revealed that the leaf cells divided into
      meristematic cells firstly, followed by somatic proembryos, and then somatic
      globular embryos. Eventually, somatic embryos developed a bipolar structure with
      the shoot apical meristem and the root meristem. Scanning electron microscopy
      observations showed that the direct somatic embryogenesis from leaf explants was
      asynchronously. The somatic embryos were found on the leaf tip, the adaxial
      surface and also the mesophyll through a cleft, and it reflected the
      heterogeneity of the explant. The 90-day-old globular embryos were detached from
      the parent explants and transferred onto a hormone-free 1/2 MS medium in light
      condition for about 1 month to obtain 1-cm-height plantlets. After another 3
      months for growth, the plantlets were potted with Sphagnum moss and were
      acclimatized in a shaded greenhouse. After 1 month of culture, the survival rate
      was 100%. CONCLUSIONS: In this report, a protocol for efficient regenerating a
      Tolumnia orchid, Louise Elmore 'Elsa', was established via direct somatic
      embryogenesis and might reveal an alternative approach for mass propagation of
      Tolumnia genus in orchid industry.

PMID- 29357025
TI  - A higher incidence of cleavage failure in oocytes containing smooth endoplasmic
      reticulum clusters.
AB  - PURPOSE: In human oocytes, sERCs are one of the dysmorphic phenotypes that have
      been reported. Significantly reduced pregnancy rates and a comparatively higher
      number of abnormities in live births appear to be associated with the presence of
      sERCs in oocytes. However, some reports have shown that healthy babies can be
      born, without any reduced pregnancy rates, from oocytes observed to contain
      sERCs. Thus, the clinical and scientific significance of oocytes that harbor
      sERCs remains controversial. METHODS: The presence of sERCs was evaluated using a
      time-lapse system while studying the dynamic changes within oocytes and embryos.
      Logistic regression analysis was carried out to explore the independent variables
      for meiotic and mitotic cleavage failure.. RESULTS: The incidence of mitotic
      cleavage failure and the incidence of meiotic cleavage failure during the second
      polar body extrusion in oocytes with sERCs were found to be significantly higher
      than that in oocytes without sERCs. Furthermore, ICSI was found to have a greater
      frequency of meiotic failure than IVF. CONCLUSIONS: In cases of cleavage failure,
      an embryonic cell could become tetraploid and may induce abnormal chromosomal
      configurations. Some cells exposed to cleavage failure may become trophectoderm
      cells and form placental abnormalities. Even if they develop into trophectoderm
      cells, the ICM can be susceptible to further cleavage failure and may in turn
      cause further aneuploidy. For these reasons, it is important to monitor
      pregnancies and births derived from oocytes that contained sERCs.

PMID- 29357026
TI  - Effect of mouse ovarian tissue cryopreservation by vitrification with Rapid-i
      closed system.
AB  - PURPOSE: Currently, open systems are mainly used for cryopreservation of ovarian
      tissue, oocytes, and embryos, but there is a potential risk of contamination.
      This study was performed to assess ovarian tissue cryopreservation by a closed
      vitrification system (Rapid-i vitrification systemTM), which is already used
      clinically for oocyte/embryo cryopreservation. METHODS: Ovaries of C57BL/6J mice
      were frozen and thawed by using the Rapid-i vitrification systemTM (Rapid-i)
      followed by implantation into recipient mice. Hematoxylin-eosin staining was
      performed for histological examination of the frozen-thawed ovaries to assess
      follicle grade. Fertility after implantation of the ovaries was assessed from the
      live birth rate and the number of live pups. RESULTS: There was no significant
      difference in grade 1 primary follicles between fresh ovaries (control group,
      94.2 +/- 2.9%) and frozen-thawed ovaries (Rapid-i group, 87.1 +/- 1.8%). However,
      there was a significant decrease in grade 1 early and late secondary follicles in
      the Rapid-i group compared with the control group. The live-birth rate was
      significantly lower in the Rapid-i group compared with the control group (29.2
      vs. 83.3%, p < 0.05). On the other hand, there was no significant difference in
      the average number of live pups between the control group and the Rapid-i group
      (3 +/- 0.4 vs. 2.7 +/- 0.3). CONCLUSIONS: The Rapid-i seems to be effective for
      cryopreservation of mouse ovarian tissue. Under appropriate conditions, the Rapid
      i could be employed for ovarian tissue cryopreservation and preservation of
      fertility in humans.

PMID- 29357028
TI  - Superpredator proximity and landscape characteristics alters nest site selection
      and breeding success of a subordinate predator.
AB  - Selecting nesting habitat that minimizes predation risk but maximizes foraging
      success is one of the most important decisions in avian life history. This takes
      on added complexity when a predator is faced with the challenge of avoiding
      fellow predators. We assessed the importance of local and landscape vegetation,
      food abundance, and predation risk on nest site selection and nest survival in a
      subordinate raptor (Mississippi Kite; Ictinia mississippiensis) nesting in
      proximity to two superpredators, Red-tailed hawk (Buteo jamaicensis) and Great
      horned owl (Bubo virginianus). All three species nested in trees in a grassland
      landscape. In this landscape, kites favored upland trees and shrubs, avoiding
      their more typical riparian forest association elsewhere in the species' range.
      Compared to random conditions, kites selected nest sites with high tree density
      and more closed canopy in the surrounding area. Mississippi Kite selection was
      not related to food abundance but could be explained by the presence of
      superpredators (i.e., hawks and owls) selecting riparian woodland for their
      nests. Nest survival declined with proximity to superpredator nesting sites.
      Overall, our study demonstrates how landscape structure and superior predators
      shapes predation risk for subordinate predators. Our results emphasize the
      importance of spatial heterogeneity in presenting opportunities for subordinate
      predators to coexist in a landscape with important superpredators.

PMID- 29357027
TI  - Longitudinal study of quality of life among children with acute respiratory
      infection and cough.
AB  - PURPOSE: Acute respiratory infections (ARIs), and associated symptoms such as
      cough, are frequently experienced among children and impose a burden on families
      (e.g., use of medical resources and time off work/school). However, there are
      little data on changes in, and predictors of, quality of life (QoL) over the
      duration of an ARI with cough (ARIwC) episode. We therefore aimed to determine
      cough-specific QoL and identify its influencing factors among children with
      ARIwC, at the time of presentation to a pediatric emergency department (ED), and
      over the following 4 weeks. METHODS: Data from 283 children aged < 15 years were
      included in our analyses. We used the validated parent-proxy children's acute
      cough-specific QoL questionnaire (PAC-QoL) at each time-point. Linear regression
      and mixed effect modeling were used to identify factors influencing QoL at
      baseline and over the follow-up period. RESULTS: Median PAC-QoL at baseline was
      2.7 (IQR 2.1-3.6) and significantly improved by Day-7 (4.9, IQR 3.8-6.1) and Day
      14 (6.59, IQR 5.1-7.0), both p < 0.001. The improvements in median PAC-QoL
      between Days-14, -21, and -28 were not significant. Regression modeling
      identified that day-cough severity, night-cough severity, and financial concerns
      had the highest impact on both baseline, and follow-up, PAC-QoL scores. There
      were five additional independent significant factors at baseline and six at
      follow-up. CONCLUSIONS: Quality of life is considerably impaired at presentation
      to ED, but improves significantly by Days-7 and -14. As cough severity and
      financial concerns had the highest impact on QoL, effectively managing cough to
      reduce the clinical and financial burden on children and families is important.

PMID- 29357029
TI  - Fine-scale movement and habitat use of a prairie stream fish assemblage.
AB  - Measuring an organism's movement and habitat use is highly dependent on the
      spatial and temporal scale of the study, with most studies measuring
      distributions once a day or at less frequent intervals. Yet, to fully understand
      the rates of intra- and interspecific encounters among individuals, observations
      at finer spatial and temporal scales might be necessary. We used passive
      integrated transponder tags and antenna arrays to continuously monitor habitat
      use and vagility of three stream minnows; southern redbelly dace Chrosomus
      erythrogaster, central stoneroller Campostoma anomalum, and creek chub Semotilus
      atromaculatus, among and within pools of an intermittent stream. Most fish
      remained in the pool where they were caught and released, or returned after
      emigrating from the pool. Despite largely remaining within the release pool,
      distribution among four microhabitats differed significantly over six, 4-h time
      periods for all three species. Vagility, the summed distance moved among
      antennas, differed significantly among species. Individual vagility (m day-1)
      increased significantly with body length for stoneroller and chub, but not dace.
      Some individuals moved as much as 110 m day-1 within the pool, showcasing
      extensive movement at fine scales. Finally, we found no evidence that feeding
      activity changed as a result of differential habitat use over a 24-h period. Our
      findings indicate considerable variation in habitat use and movement occurs among
      species over a 24-h period. This suggests ecologists can broaden the
      interpretation of processes influencing community structure (e.g., resource
      partitioning, avoidance of predators) by quantifying species distributions across
      a range of spatial and temporal scales.

PMID- 29357030
TI  - Seed supply limits seedling recruitment of Eucalyptus miniata: interactions
      between seed predation by ants and fire in the Australian seasonal tropics.
AB  - Seed predation can cause substantial seed losses and influence plant population
      dynamics, but the impact depends on the extent to which populations are limited
      by seed availability or favorable microsites for recruitment. Harvester ants are
      the dominant post-dispersal seed predators in Australia's tropical savannas, and
      their abundance and foraging efficiency, as well as the availability of seed and
      microsites, are affected by fire history. We undertook a predator-exclusion
      experiment to examine the interactive effects of fire history (no fire compared
      with annual burning over 5 years) and seed predation by ants on seedling
      establishment of the dominant savanna tree, Eucalyptus miniata, in northern
      Australia. Despite its large seed size, the rate of removal (~ 20-60%) was
      similar or higher than typically reported for eucalypts, although it was lower
      than that recorded for the smaller seeds of the co-occurring E. tetrodonta. Seed
      predation rates were twice as high in annually burnt compared to unburnt sites,
      but there was no significant difference in the proportion of seedlings that
      emerged from the initial seed available. Seedling emergence in both regimes was
      low, representing < 7% of seed available after harvesting. About one-third of
      emergent seedlings were still alive during the middle of the following dry
      season. Our results indicate that seedling recruitment in E. miniata is limited
      by both seed supply and microsite availability. However, seed predation by ants
      reduces the likelihood of seedling establishment from low to virtually zero,
      which suggests that it plays a potentially important role in the population
      dynamics of savanna eucalypts.

PMID- 29357031
TI  - A natural history model of New England salt marsh die-off.
AB  - Natural history gave birth to ecology and evolutionary biology, but today its
      importance is sometimes marginalized. Natural history provides context for
      ecological research, a concept that we illustrate using a consumer-driven
      vegetation die-off case study. For three decades, local predator depletion
      promoted the formation of high-density crab (Sesarma reticulatum) grazing and
      burrowing fronts, resulting in the spread of vegetation die-off through southern
      New England and Long Island marshes. We review results from a decade of research
      on this phenomenon and synthesize these findings with new field surveys,
      experiments, and historical reconstructions to test the hypothesis that the
      locations and processes of vegetation die-off and recovery are spatially
      predictable. We discovered that crab-driven die-off consistently begins on marsh
      creek heads, where peat and high flow conditions overlap, before spreading to
      inner creeks following peat availability, stunted cordgrass, and flow.
      Eventually, die-off eliminates most low marsh vegetation, leaving behind
      unvegetated substrate too soft to support burrows. Vegetation recovery exhibits
      the reverse patterns of die-off; it consistently begins in the low marsh within
      inner creeks, where soft substrate and low flow conditions overlap, before
      spreading to creek heads. This spatially explicit, substrate-dependent recovery
      eventually leads to ungrazed cordgrass abutting grazed cordgrass on the high
      marsh border. We present a conceptual model of die-off through recovery
      progression to provide managers and landowners with a diagnostic tool for
      identifying marsh die-off and recovery status. Collectively, this work
      illustrates the fundamental importance of long-term, natural history-based
      investigations of ecosystem dynamics in informing ecology, conservation, and
      management practices.

PMID- 29357033
TI  - The effects of resveratrol on markers of oxidative stress in patients with type 2
      diabetes: a randomized, double-blind, placebo-controlled clinical trial.
AB  - AIMS: Oxidative stress plays a pivotal role in the pathogenesis of type 2
      diabetes (T2D). In vitro and animal studies have shown that resveratrol exerts an
      antioxidant effect, but clinical trials addressing this effect in patients with
      T2D are limited. The aim of this study was to determine whether resveratrol
      supplementation affects oxidative stress markers in a randomized, placebo
      controlled, double-blind clinical trial. METHODS: A total of 48 patients with T2D
      randomly were assigned to receive 800 mg/day resveratrol or placebo for 2 months.
      Plasma total antioxidant capacity, malondialdehyde concentration, protein
      carbonyl and total thiol contents, intracellular superoxide anion (O2-.) and
      hydrogen peroxide (H2O2) in PBMCs, the expression of genes involved in oxidative
      stress responses (Nrf2, SOD, Cat, HO-1, RAGE, NOS) in PBMCs, and metabolic and
      anthropometric parameters were measured at the baseline and at the trial end.
      RESULTS: Compared with the placebo group, resveratrol reduced plasma protein
      carbonyl content and PBMCs O2-. level and significantly increased plasma total
      antioxidant capacity and total thiol content. Furthermore, the expression of Nrf2
      and SOD was significantly increased after resveratrol consumption. Resveratrol
      had no significant effects on the metabolic and anthropometric parameters except
      for a significant reduction in weight, BMI, and blood pressure levels.
      Resveratrol was well tolerated, and no serious adverse event was occurred.
      CONCLUSIONS: Our study demonstrated that 8 weeks of supplementation with 800
      mg/day resveratrol has an antioxidant effect in the blood and PBMCs of patients
      with T2D. Clinical Trial Registry number and website IRCT registration number:
      IRCT2015072523336N1 and http://en.search.irct.ir/view/24752 .

PMID- 29357032
TI  - Seagrass collapse due to synergistic stressors is not anticipated by phenological
      changes.
AB  - Seagrasses are globally declining and often their loss is due to synergies among
      stressors. We investigated the interactive effects of eutrophication and burial
      on the Mediterranean seagrass, Posidonia oceanica. A field experiment was
      conducted to estimate whether shoot survival depends on the interactive effects
      of three levels of intensity of both stressors and to identify early changes in
      plants (i.e., morphological, physiological and biochemical, and expression of
      stress-related genes) that may serve to detect signals of imminent shoot density
      collapse. Sediment burial and nutrient enrichment produced interactive effects on
      P. oceanica shoot survival, as high nutrient levels had the potential to
      accelerate the regression of the seagrass exposed to high burial (HB). After 11
      weeks, HB in combination with either high or medium nutrient enrichment caused a
      shoot loss of about 60%. Changes in morphology were poor predictors of the
      seagrass decline. Likewise, few biochemical variables were associated with P.
      oceanica survival (the phenolics, ORAC and leaf delta34S). In contrast, the
      expression of target genes had the highest correlation with plant survival:
      photosynthetic genes (ATPa, psbD and psbA) were up-regulated in response to high
      burial, while carbon metabolism genes (CA-chl, PGK and GADPH) were down
      regulated. Therefore, die-offs due to high sedimentation rate in eutrophic areas
      can only be anticipated by altered expression of stress-related genes that may
      warn the imminent seagrass collapse. Management of local stressors, such as
      nutrient pollution, may enhance seagrass resilience in the face of the
      intensification of extreme climate events, such as floods.

PMID- 29357034
TI  - Prevalence and management of diabetes in immigrants resident in the Lombardy
      Region: the importance of ethnicity and duration of stay.
AB  - AIMS: To describe the prevalence and management of diabetes among immigrants
      according to ethnic group and duration of stay, compared to Italian citizens.
      METHODS: Diabetic immigrant and Italian residents aged 20-69 years in the
      administrative database of the Lombardy Region. Immigrants were classified by
      region of origin and as long-term residents (LTR) and short-term residents (STR).
      Age- and sex-adjusted prevalence and indicators of diabetes management were
      calculated for immigrants by region of origin and by length of stay using Cox
      proportional models. RESULTS: In 2010 19,992 immigrants (mean age 49.1 +/- 10.8,
      53.7% males) and 195,049 Italians (mean age 58.7 +/- 9.3, 61.1 males) with
      diabetes were identified. Immigrants had a higher adjusted diabetes prevalence
      than Italians (OR 1.48; 95% CI 1.45-1.50). STR received significantly fewer
      recommended cardiovascular drugs (antiplatelets, statins and ACE-inhibitors/ARBs)
      than Italians, although prescription was higher among LTR from some ethnic
      groups. Immigrants were less likely to be seen by a diabetologist and to do at
      least one HbA1c test per year. Although the recommended tests/visits were more
      often done for the LTR than the STR, in the majority of ethnic groups these
      indicators were still far from optimal. CONCLUSION: The prevalence and management
      of diabetes differ between immigrants and Italians, although some improvement can
      be seen among LTR.

PMID- 29357035
TI  - Cryptogenic acute limb ischemia: a retrospective cohort study defining a
      previously undescribed clinical entity.
AB  - Acute limb ischemia (ALI) is generally secondary to cardioembolism or progression
      of peripheral vascular disease, however, a discrete population of patients with
      ALI exists in which no precipitant is ever established. Unlike cryptogenic
      arterial occlusion in other arenas, such as cryptogenic stroke, cryptogenic acute
      limb ischemia (cALI) has not been well-described, and no routine management has
      been established. The aim of this study is to describe patients with cALI, and
      the risk of recurrence based on the treatment they received. We performed a
      retrospective cohort study of patients evaluated for ALI at a single academic
      center, excluding patients with known peripheral artery disease, polytrauma,
      critical illness, or a history of recent vascular access. Out of 608 individual
      patients analyzed, 37 were deemed to have cALI on their initial presentation.
      After extended follow up, 29 patients were eventually found to have a
      precipitating cause, with 8 patients remaining cryptogenic. On follow up, the
      overall rate of recurrent ALI was 13% in the group eventually found to have a
      precipitating cause, and 25% in the cALI group. The median time to recurrence was
      16.5 months in the precipitated acute limb ischemia (pALI) group, and 23.3 months
      in the cALI group. Of pALI patients who recurred, 40% did so despite being
      therapeutic on anticoagulation. None of the recurring cALI patients were
      therapeutically anticoagulated. Based on our analysis, nearly 20% of patients
      presenting with ALI in the absence of known risk factors will remain cryptogenic.
      Rates of recurrent ALI in patients who present with cALI are significant,
      particularly in patients who are not maintained on anticoagulation. This suggests
      that the etiology of ALI in patients without peripheral vascular disease may not
      have a strong bearing on treatment decisions, and that indefinite anticoagulation
      may be warranted in patients with no obvious cause on presentation. Future
      studies are needed to better gauge the risk for bleeding complications and to
      provide a better understanding of the risks and benefits of recurrence and
      complications of anticoagulation over time.

PMID- 29357036
TI  - Recent transmission of Mycobacterium tuberculosis in China: the implication of
      molecular epidemiology for tuberculosis control.
AB  - Tuberculosis (TB) has remained an ongoing concern in China. The national scale-up
      of the Directly Observed Treatment, Short Course (DOTS) program has accelerated
      the fight against TB in China. Nevertheless, many challenges still remain,
      including the spread of drug-resistant strains, high disease burden in rural
      areas, and enormous rural-to-urban migrations. Whether incident active TB
      represents recent transmission or endogenous reactivation has helped to
      prioritize the strategies for TB control. Evidence from molecular epidemiology
      studies has delineated the recent transmission of Mycobacterium tuberculosis (M.
      tuberculosis) strains in many settings. However, the transmission patterns of TB
      in most areas of China are still not clear. Studies carried out to date could not
      capture the real burden of recent transmission of the disease in China because of
      the retrospective study design, incomplete sampling, and use of low-resolution
      genotyping methods. We reviewed the implementations of molecular epidemiology of
      TB in China, the estimated disease burden due to recent transmission of M.
      tuberculosis strains, the primary transmission of drug-resistant TB, and the
      evaluation of a feasible genotyping method of M. tuberculosis strains in
      circulation.

PMID- 29357037
TI  - Blood-threshold CMR volume analysis of functional univentricular heart.
AB  - PURPOSE: To validate a blood-threshold (BT) segmentation software for cardiac
      magnetic resonance (CMR) cine images in patients with functional univentricular
      heart (FUH). MATERIALS AND METHODS: We evaluated retrospectively 44 FUH patients
      aged 25 +/- 8 years (mean +/- standard deviation). For each patient, the
      epicardial contour of the single ventricle was manually segmented on cine images
      by two readers and an automated BT algorithm was independently applied to
      calculate end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume
      (SV), ejection fraction (EF), and cardiac mass (CM). Aortic flow analysis (AFA)
      was performed on through-plane images to obtain forward volumes and used as a
      benchmark. Reproducibility was tested in a subgroup of 24 randomly selected
      patients. Wilcoxon, Spearman, and Bland-Altman statistics were used. RESULTS: No
      significant difference was found between SV (median 57.7 ml; interquartile range
      47.9-75.6) and aortic forward flow (57.4 ml; 48.9-80.4) (p = 0.123), with a high
      correlation (r = 0.789, p < 0.001). Intra-reader reproducibility was 86% for SV
      segmentation, and 96% for AFA. Inter-reader reproducibility was 85 and 96%,
      respectively. CONCLUSION: The BT segmentation provided an accurate and
      reproducible assessment of heart function in FUH patients.

PMID- 29357039
TI  - Evolution of post-mortem coronary imaging: from selective coronary arteriography
      to post-mortem CT-angiography and beyond.
AB  - Since the 1970s, remarkable efforts have been made in the post-mortem coronary
      study, especially by angiography, as an added tool to diagnose heart-related
      deaths. In more recent times, post-mortem CT (PMCT) and post-mortem CT
      angiography (PMCTA) have become an established practice in numerous forensic
      units, because of the undeniable advantages these diagnostic instruments can
      offer: data acquisition times are increasingly fast, costs have become lower and,
      once acquired, data can be re-utilized and re-evaluated at any given time. This
      review aims to chart the history of post-mortem cardiac imaging, highlighting its
      evolution both in terms of methodology and technology as well as the contribution
      that forensic radiology has been able to offer to forensic pathology, not as an
      alternative to autopsy but as a guide and aid when performing one. Finally, the
      latest advances in the study of cardiac deaths are explored, namely by cardiac
      post-mortem MRI (PMMR), able to visualize all the various stages of a myocardial
      infarction, post-mortem MRI-angiography (PMMRA), useful in investigating coronary
      artery pathology and post-mortem cardiac micro-CT, able to provide near
      histological levels of myocardial, coronary and valvular detail.

PMID- 29357038
TI  - Uterine fibroid embolization efficacy and safety: 15 years experience in an
      elevated turnout rate center.
AB  - OBJECTIVE: To evaluate effectiveness and safety of UFE as alternative to surgery,
      in treatment of uterine fibromatosis. METHODS/MATERIALS: 255 patients (aged 26
      55) with symptomatic UF, indication for surgery, followed in our center (2000
      2014), single or multiple fibroids, pain and/or functional/compressive disorders,
      underwent embolization: injection of PVA particles (150-900 MUm) from distal
      portion of uterine arteries (ascending section). Primary end-point: flow-stop
      distally to injection site, disappearance of lesion design, preservation of flow
      in main trunk of UA. Secondary end-point: control of pain and
      functional/compressive disorders during follow-up (2-7 years). RESULTS: Procedure
      was performed bilaterally in 250 patients (98%). Mean duration: 47 min (average
      fluoroscopy: 10:50 min). Post-embolization pelvic pain (according with VAS score)
      was on average 2.2 at discharge (24 h). Follow-up at 2 years: resolution of
      menstrual disorders in 78% of patients and improvement in 14%; pain disappeared
      in 66%; significant improvement of menstrual flow and HCT/HB levels, decrease in
      total uterine (57.7%)/dominant fibroid (76.1%) volume. Recurrence in 18 patients.
      CONCLUSIONS: UFE represents an excellent alternative to surgical treatment: it is
      safe, tolerable and effective both in short and long term, with evident
      advantages in economic and social terms.

PMID- 29357040
TI  - Hepatic cavernous hemangiomas: long-term (> 5 years) follow-up changes on
      contrast-enhanced dynamic computed tomography or magnetic resonance imaging and
      determinant factors of the size change.
AB  - PURPOSE: To investigate the very long-term (> 5 years) follow-up changes of
      hepatic cavernous hemangiomas and to evaluate possible determinant factors for
      the changes. MATERIALS AND METHODS: Among 1115 consecutive patients suspected of
      having hepatic hemangiomas based on imaging features, 101 patients with
      comparable computed tomography or magnetic resonance imaging data during a 5-year
      follow-up interval in the Picture Archiving and Communication System were
      analyzed. Two radiologists independently determined the largest dimension of each
      lesion on axial images. In addition to background liver fibrosis or steatosis on
      imaging, histories of use of chemotherapeutic agents were checked from the
      patients' records. The final size change of the hemangioma was categorized into
      three groups compared with the initial diameter (increased, > 120%; no change, 80
      120%; decreased, < 80%). RESULTS: Among the 101 hemangiomas, 32 lesions (31.7%)
      were enlarged and 21 lesions (20.8%) were shrunken during intervals of 60-157
      (median, 81) months. Younger patients showed a higher prevalence of lesion
      enlargement (mean age: enlarged, 47.3 years; no change, 52.8 years; shrunken,
      57.1 years; p = 0.003). In 15 patients with cirrhosis, the lesions (shrunken, n =
      7; enlarged, n = 1) showed a higher tendency of size decrease (p = 0.009),
      whereas other factors did not show statistical significance (p > 0.05). Only a
      minor proportion (1%, n = 1) of the lesions showed size fluctuation during follow
      up. CONCLUSION: During the long-term (5-13 years) follow-up, about 50% of the
      hepatic hemangiomas were enlarged or shrunken to > 20% of the initial diameter.
      Aside from the cirrhosis and aging factors, the size changes seemed sporadic.

PMID- 29357042
TI  - Nimura lecture: "Three EBMs".
AB  - The three EBMs in the title refer to the following concepts: evidence-based
      medicine, experience-based medicine, and echo-based medicine. Evidence-based
      medicine: I have carried out the following clinical research using transthoracic
      Doppler echocardiography: (1) noninvasive pulsed-wave Doppler echocardiographic
      detection of the direction of shunt flow in patients with atrial septal defect:
      usefulness of the right parasternal approach (1985), (2) significance of laminar
      systolic regurgitant flow in patients with tricuspid regurgitation: a combined
      pulsed-wave, continuous-wave, and two-dimensional echocardiography (1990), (3)
      obstruction of the inferior vena caval orifice by the giant left atrium in
      patients with mitral stenosis: a Doppler echocardiographic study from the right
      parasternal approach (1992), and (4) demonstration of a localized acceleration
      flow signal in the transmural penetrating coronary artery using transthoracic
      color and pulsed-wave Doppler echocardiography in patients with hypertrophic
      cardiomyopathy (1996-2017). Experience-based medicine: Dr. Eugene Braunwald says
      "The best book of cardiology is the patient itself." I have conducted my modest
      research activities gleaning hints through day-to-day routine work and sometimes
      investigating experimentally using the Doppler echocardiographic method. I have
      also learned from the Japanese Society of Echocardiography that a physician
      should stand between evidence-based medicine and experience-based medicine. Echo
      based medicine: This term is intended to express my personal determination. I
      believe that echocardiography is the stethoscope of the 21st century. It is a
      safe, painless, low-cost, and repeatable tool at the bedside. I expect that
      echocardiography can reduce unnecessary healthcare costs and appropriately select
      reasonable examinations for patients. I would like to devote the time left in my
      career to the study of cardiovascular medicine, believing in the power of
      echocardiography and the Doppler method to provide a link between evidence-based
      medicine and experience-based medicine.

PMID- 29357041
TI  - Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after
      Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs.
AB  - Remote damage is a secondary phenomenon that usually occurs after a primary brain
      damage in regions that are distant, yet functionally connected, and that is
      critical for determining the outcomes of several CNS pathologies, including
      traumatic brain and spinal cord injuries. The understanding of remote damage
      associated mechanisms has been mostly achieved in several models of focal brain
      injury such as the hemicerebellectomy (HCb) experimental paradigm, which helped
      to identify the involvement of many key players, such as inflammation, oxidative
      stress, apoptosis and autophagy. Currently, few interventions have been shown to
      successfully limit the progression of secondary damage events and there is still
      an unmet need for new therapeutic options. Given the emergence of the novel
      concept of resolution of inflammation, mediated by the newly identified omega3
      derived specialized pro-resolving lipid mediators, such as resolvins, we reported
      a reduced ability of HCb-injured animals to produce resolvin D1 (RvD1) and an
      increased expression of its target receptor ALX/FPR2 in remote brain regions. The
      in vivo administration of RvD1 promoted functional recovery and neuroprotection
      by reducing the activation of Iba-1+ microglia and GFAP+ astrocytes as well as by
      impairing inflammatory-induced neuronal cell death in remote regions. These
      effects were counteracted by intracerebroventricular neutralization of ALX/FPR2,
      whose activation by RvD1 also down-regulated miR-146b- and miR-219a-1-dependent
      inflammatory markers. In conclusion, we propose that innovative therapies based
      on RvD1-ALX/FPR2 axis could be exploited to curtail remote damage and enable
      neuroprotective effects after acute focal brain damage.

PMID- 29357043
TI  - Cell wall layers delimit cell groups derived from cell division in the foliose
      trebouxiophycean alga Prasiola japonica.
AB  - The cells in the foliose thallus of trebouxiophycean alga Prasiola japonica
      apparently develop into 2 * 2 cell groups composed of two two-celled groups, each
      of which is a pair of derivative cells of the latest cell division. In the
      present study, the structural features of cell walls of the alga P. japonica
      concerning the formation of the cell groups were investigated using histochemical
      methods. Thin cell layers stained by Calcofluor White appeared to envelope the
      two-celled and four-celled groups separately and, hence, separated them from
      neighboring cell groups, and the Calcofluor White-negative gaps between
      neighboring four-celled groups were specifically stained by lectins, such as
      soybean agglutinin, jacalin, and Vicia villosa lectin conjugated with
      fluorescein. These results indicated that the Calcofluor White-positive cell wall
      layer of parent cell that existed during two successive cell divisions
      structurally distinguished two-celled and four-celled groups from others in this
      alga. Moreover, the results suggested that the cell wall components of the
      Calcofluor White-negative gaps would possibly contribute to the formation of the
      planar thallus through lateral union of the cell groups.

PMID- 29357044
TI  - Greetings from the New Editor.

PMID- 29357045
TI  - Religion and Spirituality as a Cultural Asset in Medical Students.
AB  - We explored the ways that religion and spirituality (R/S) work as a cultural
      asset in the lives of medical students and how students anticipate using this
      asset as physicians. A group of sixteen religiously diverse medical students were
      interviewed, and data were analyzed using grounded theory. The results indicate
      that regardless of faith, students repurposed their R/S to help them cope with
      the stress of medical school, make clinical decisions, resolve inexplicable
      events, and practice patient-centered care. Medical educators should leverage
      this asset to help students understand how to practice in ways that are
      consistent with patient-centered care.

PMID- 29357046
TI  - Translational neonatology research: transformative encounters across species and
      disciplines.
AB  - This paper explores the laborious and intimate work of turning bodies of research
      animals into models of human patients. Based on ethnographic research in the
      interdisciplinary Danish research centre NEOMUNE, we investigate collaboration
      across species and disciplines, in research aiming at improving survival for
      preterm infants. NEOMUNE experimental studies on piglets evolved as a platform on
      which both basic and clinical scientists exercised professional authority. Guided
      by the field of multi-species research, we explore the social and material agency
      of research animals in the production of human health. Drawing on Anna Tsing's
      concept of "collaborative survival", we show that sharing the responsibility of
      the life and death of up to twenty-five preterm piglets fostered not only a
      collegial solidarity between basic and clinical scientists, but also a
      transformative cross-fertilization across species and disciplines-a productive
      "contamination"-facilitating the day-to-day survival of piglets, the academic
      survival of scientists and the promise of survival of preterm infants.
      Contamination spurred intertwined identity shifts that increased the porosity
      between the pig laboratory and the neonatal intensive care unit. Of particular
      significance was the ability of the research piglets to flexibly become animal
      infant-patient hybrids in need of a united effort from basic and clinical
      researchers. However, 'hybrid pigs' also entailed a threat to the demarcation
      between humans and animals that consolidates the use of animals in biomedical
      research, and efforts were continuously done to keep contamination within spatial
      limits. We conclude that contamination facilitates transformative encounters, yet
      needs spatial containment to materialize bench-to-bedside translation.

PMID- 29357047
TI  - Human Decisions in Moral Dilemmas are Largely Described by Utilitarianism:
      Virtual Car Driving Study Provides Guidelines for Autonomous Driving Vehicles.
AB  - Ethical thought experiments such as the trolley dilemma have been investigated
      extensively in the past, showing that humans act in utilitarian ways, trying to
      cause as little overall damage as possible. These trolley dilemmas have gained
      renewed attention over the past few years, especially due to the necessity of
      implementing moral decisions in autonomous driving vehicles (ADVs). We conducted
      a set of experiments in which participants experienced modified trolley dilemmas
      as drivers in virtual reality environments. Participants had to make decisions
      between driving in one of two lanes where different obstacles came into view.
      Eventually, the participants had to decide which of the objects they would crash
      into. Obstacles included a variety of human-like avatars of different ages and
      group sizes. Furthermore, the influence of sidewalks as potential safe harbors
      and a condition implicating self-sacrifice were tested. Results showed that
      participants, in general, decided in a utilitarian manner, sparing the highest
      number of avatars possible with a limited influence by the other variables.
      Derived from these findings, which are in line with the utilitarian approach in
      moral decision making, it will be argued for an obligatory ethics setting
      implemented in ADVs.

PMID- 29357048
TI  - The role of calcium, silicon and salicylic acid treatment in protection of canola
      plants against boron toxicity stress.
AB  - Boron (B) toxicity often limits crop yield and the quality of production in
      agricultural areas. Here, we investigated the effects of calcium (Ca), silicon
      (Si) and salicylic acid (SA) on development of B toxicity, B allocation in canola
      (Brassica napus cultivar Sarw 4) and its role in non-enzymatic antioxidants in
      relation to yield of this cultivar under B toxicity. Canola seedlings were
      subjected to four B levels induced by boric acid in the absence or presence of
      Ca, Si and SA. The results showed that Ca, Si and SA addition ameliorated the
      inhibition in canola growth, water content (WC), and improved siliqua number,
      siliqua weight and seed index. The B content in shoots and roots and total B
      accumulation in the whole plant were increased in control plants under B-toxicity
      stress, and these parameters were significantly decreased by addition of Ca, Si
      and SA. The shoot ascorbate pool (ascorbate, AsA, and dehydroascorbate, DHA),
      alpha-tocopherol and phenolics (free and bound) were increased under B toxicity,
      and were significantly decreased in most cases by addition of Ca, Si and SA,
      except alpha-tocopherol, which increased at low B levels (0, 25 and 50 mg kg soil
      1). The glutathione content did not obviously change by B stress, while added Ca,
      Si and SA inhibited its accumulation under B stress. In addition, B toxicity
      reduced the shoot flavonoids content; however, this reduction was not alleviated
      by the use of Ca, Si and SA treatments. It could be concluded that growth and
      yield of canola plants grown under high B concentration improved after external
      application of Ca, Si or SA.

PMID- 29357049
TI  - Multiple small bowel perforations due to invasive aspergillosis in a patient with
      acute myeloid leukemia: case report and a systematic review of the literature.
AB  - PURPOSE: Invasive aspergillosis (IA) represents a major cause of morbidity and
      mortality in immunocompromised patients. Involvement of the gastrointestinal
      tract by Aspergillus is mostly reported as part of a disseminated infection from
      a primary pulmonary site and only rarely as an isolated organ infection. METHODS:
      We report a case of small bowel perforation due to IA in a patient with acute
      leukemia under chemotherapy and pulmonary aspergillosis. We performed a
      systematic review of the literature as well. RESULTS: A 43-year-old man with
      acute myeloid leukemia under chemotherapy developed severe neutropenia and
      pulmonary aspergillosis due to Aspergillus flavus. He developed melena and
      hemodynamic failure and a contrast-enhanced ultrasound scan suggested active
      intestinal bleeding. During emergency laparotomy we found multiple intestinal
      abscesses, several perforations of intestinal loop and Aspergillus flavus was
      isolated from the abscesses. Resection of the jejunum was performed. The patient
      received voriconazole and finally recovered. The patient is now alive and in
      complete disease remission. From literature review we found 35 intestinal IA
      previously published in single case reports or small case series as well.
      CONCLUSION: Clinical manifestations of gastrointestinal aspergillosis are
      nonspecific, such as abdominal pain, and only occasionally it presents as an
      acute abdomen. Antemortem detection of bowel involvement is rarely achieved and,
      only in cases of complicated gastrointestinal aspergillosis, the diagnosis is
      achieved thanks to the findings during surgery. Gastrointestinal aspergillosis
      should be suspected in patients with severe and prolonged neutropenia with or
      without pulmonary involvement in order to consider the right therapy and prompt
      surgery.

PMID- 29357050
TI  - Clinical variation in the use of echocardiography in Staphylococcus aureus
      bacteraemia: a multi-centre cohort study.
AB  - The objective of this investigation was to assess whether between-hospital
      variation in echocardiography usage for patients with Staphylococcus aureus
      bacteraemia (SAB) is explained by differences in patients' pre-test probability
      of endocarditis. This was a retrospective cohort study at three neighbouring
      hospitals in Australia. Consecutive episodes of SAB were reviewed for the
      presence of three endocarditis risk factors (community onset, prolonged
      bacteraemia and the presence of an intracardiac prosthetic device) and the
      performance and results of all echocardiography studies within 30 days.
      Multivariate logistic regression was used to examine the effect of hospital site
      on the performance of (i) transoesophageal and (ii) transthoracic
      echocardiography controlling for major endocarditis risk factors. Significant
      variation in echocardiography usage was demonstrated between sites in a total
      cohort of 1167 episodes of SAB. None of the three sites were found to exhibit
      echocardiography usage that could be considered consistent with current
      guidelines, and each differed from the guidelines in different ways. Hospital
      site, rather than endocarditis risk factors, was the strongest predictor of
      transthoracic echocardiography use; however, the use of transoesophageal
      echocardiography was strongly predicted by endocarditis risk factors. Variation
      in echocardiography use between these hospitals is not adequately explained by
      differences in the risk factor profile of their SAB cohorts.

PMID- 29357051
TI  - Historical Perspective of Eukaryotic DNA Replication.
AB  - The replication of the genome of a eukaryotic cell is a complex process requiring
      the ordered assembly of multiprotein replisomes at many chromosomal sites. The
      process is strictly controlled during the cell cycle to ensure the complete and
      faithful transmission of genetic information to progeny cells. Our current
      understanding of the mechanisms of eukaryotic DNA replication has evolved over a
      period of more than 30 years through the efforts of many investigators. The aim
      of this perspective is to provide a brief history of the major advances during
      this period.

PMID- 29357052
TI  - Regulation of Replication Origins.
AB  - In eukaryotes, genome duplication starts concomitantly at many replication
      initiation sites termed replication origins. The replication initiation program
      is spatially and temporally coordinated to ensure accurate, efficient DNA
      synthesis that duplicates the entire genome while maintaining other chromatin
      dependent functions. Unlike in prokaryotes, not all potential replication origins
      in eukaryotes are needed for complete genome duplication during each cell cycle.
      Instead, eukaryotic cells vary the use of initiation sites so that only a
      fraction of potential replication origins initiate replication each cell cycle.
      Flexibility in origin choice allows each eukaryotic cell type to utilize
      different initiation sites, corresponding to unique nuclear DNA packaging
      patterns. These patterns coordinate replication with gene expression and
      chromatin condensation. Budding yeast replication origins share a consensus
      sequence that marks potential initiation sites. Metazoan origins, on the other
      hand, lack a consensus sequence. Rather, they are associated with a collection of
      structural features, chromatin packaging features, histone modifications,
      transcription, and DNA-DNA/DNA-protein interactions. These features confer cell
      type-specific replication and expression and play an essential role in
      maintaining genomic stability.

PMID- 29357053
TI  - Molecular Mechanism for Chromatin Regulation During MCM Loading in Mammalian
      Cells.
AB  - DNA replication is a fundamental process required for the accurate and timely
      duplication of chromosomes. During late mitosis to G1 phase, the MCM2-7 complex
      is loaded onto chromatin in a manner dependent on ORC, CDC6, and Cdt1, and
      chromatin becomes licensed for replication. Although every eukaryotic organism
      shares common features in replication control, there are also some differences
      among species. For example, in higher eukaryotic cells including human cells, no
      strict sequence specificity has been observed for replication origins, unlike
      budding yeast or bacterial replication origins. Therefore, elements other than
      beyond DNA sequences are important for regulating replication. For example, the
      stability and precise positioning of nucleosomes affects replication control.
      However, little is known about how nucleosome structure is regulated when
      replication licensing occurs. During the last decade, histone acetylation enzyme
      HBO1, chromatin remodeler SNF2H, and histone chaperone GRWD1 have been identified
      as chromatin-handling factors involved in the promotion of replication licensing.
      In this review, we discuss how the rearrangement of nucleosome formation by these
      factors affects replication licensing.

PMID- 29357054
TI  - Initiation of DNA Replication at the Chromosomal Origin of E. coli, oriC.
AB  - The Escherichia coli chromosomal origin consists of a duplex-unwinding region and
      a region bearing a DNA-bending protein, IHF-binding site, and clusters of binding
      sites for the initiator protein DnaA. ATP-DnaA molecules form highly organized
      oligomers in a process stimulated by DiaA, a DnaA-binding protein. The resultant
      ATP-DnaA complexes promote local unwinding of oriC with the aid of IHF, for which
      specific interaction of DnaA with the single-stranded DNA is crucial. DnaA
      complexes also interact with DnaB helicases bound to DnaC loaders, promoting
      loading of DnaB onto the unwound DNA strands for bidirectional replication.
      Initiation of replication is strictly regulated during the cell cycle by multiple
      regulatory systems for oriC and DnaA. The activity of oriC is regulated by its
      methylation state, whereas that of DnaA depends on the form of the bound
      nucleotide. ATP-DnaA can be yielded from initiation-inactive ADP-DnaA in a timely
      manner depending on specific chromosomal DNA elements termed DARS (DnaA
      reactivating sequences). After initiation, DnaA-bound ATP is hydrolyzed by two
      systems, yielding ADP-DnaA. In this review, these and other mechanisms of
      initiation and its regulation in E. coli are described.

PMID- 29357055
TI  - Initiation of DNA Replication in the Archaea.
AB  - Organisms within the archaeal domain of life possess a simplified version of the
      eukaryotic DNA replication machinery. While some archaea possess a bacterial-like
      mode of DNA replication with single origins of replication per chromosome, the
      majority of species characterized to date possess chromosomes with multiple
      replication origins. Genetic, structural, and biochemical studies have revealed
      the nature of archaeal origin specification. Recent work has begun to shed light
      on the mechanisms of replication initiation in these organisms.

PMID- 29357056
TI  - Mechanism of Lagging-Strand DNA Replication in Eukaryotes.
AB  - This chapter focuses on the enzymes and mechanisms involved in lagging-strand DNA
      replication in eukaryotic cells. Recent structural and biochemical progress with
      DNA polymerase alpha-primase (Pol alpha) provides insights how each of the
      millions of Okazaki fragments in a mammalian cell is primed by the primase
      subunit and further extended by its polymerase subunit. Rapid kinetic studies of
      Okazaki fragment elongation by Pol delta illuminate events when the polymerase
      encounters the double-stranded RNA-DNA block of the preceding Okazaki fragment.
      This block acts as a progressive molecular break that provides both time and
      opportunity for the flap endonuclease 1 (FEN1) to access the nascent flap and cut
      it. The iterative action of Pol delta and FEN1 is coordinated by the replication
      clamp PCNA and produces a regulated degradation of the RNA primer, thereby
      preventing the formation of long-strand displacement flaps. Occasional long flaps
      are further processed by backup nucleases including Dna2.

PMID- 29357057
TI  - Functions of Multiple Clamp and Clamp-Loader Complexes in Eukaryotic DNA
      Replication.
AB  - Proliferating cell nuclear antigen (PCNA) and replication factor C (RFC) were
      identified in the late 1980s as essential factors for replication of simian virus
      40 DNA in human cells, by reconstitution of the reaction in vitro. Initially,
      they were only thought to be involved in the elongation stage of DNA replication.
      Subsequent studies have demonstrated that PCNA functions as more than a
      replication factor, through its involvement in multiple protein-protein
      interactions. PCNA appears as a functional hub on replicating and replicated
      chromosomal DNA and has an essential role in the maintenance genome integrity in
      proliferating cells.Eukaryotes have multiple paralogues of sliding clamp, PCNA
      and its loader, RFC. The PCNA paralogues, RAD9, HUS1, and RAD1 form the
      heterotrimeric 9-1-1 ring that is similar to the PCNA homotrimeric ring, and the
      9-1-1 clamp complex is loaded onto sites of DNA damage by its specific loader
      RAD17-RFC. This alternative clamp-loader system transmits DNA-damage signals in
      genomic DNA to the checkpoint-activation network and the DNA-repair
      apparatus.Another two alternative loader complexes, CTF18-RFC and ELG1-RFC, have
      roles that are distinguishable from the role of the canonical loader, RFC. CTF18
      RFC interacts with one of the replicative DNA polymerases, Polepsilon, and loads
      PCNA onto leading-strand DNA, and ELG1-RFC unloads PCNA after ligation of lagging
      strand DNA. In the progression of S phase, these alternative PCNA loaders
      maintain appropriate amounts of PCNA on the replicating sister DNAs to ensure
      that specific enzymes are tethered at specific chromosomal locations.

PMID- 29357058
TI  - Termination of Eukaryotic Replication Forks.
AB  - Termination of DNA replication forks takes place when two replication forks
      coming from neighbouring origins meet each other usually in the midpoint of the
      replicon. At this stage, the remaining fragments of DNA have to be unwound, all
      remaining DNA replicated and newly synthesised strands ligated to produce
      continuous sister chromatids. Finally, the replication machinery has to be taken
      off, chromatin re-assembled, and entwisted sister chromatids resolved
      topologically.Over the last few decades, we have learned a lot about the assembly
      of the helicase and replisome and the initiation stage of DNA replication. We
      also know much more about the ability of forks to cope with replication stress.
      However, only within recent years we have gained the first glimpse of the
      mechanism of replication fork termination. In this chapter I will summarise the
      recent findings on replication termination, weigh this against the past
      literature and discuss relevant consequences and views for the future.

PMID- 29357059
TI  - Structure of the MCM2-7 Double Hexamer and Its Implications for the Mechanistic
      Functions of the Mcm2-7 Complex.
AB  - The eukaryotic minichromosome maintenance 2-7 complex is the core of the inactive
      MCM replication licensing complex and the catalytic core of the Cdc45-MCM-GINS
      replicative helicase. The years of effort to determine the structure of parts or
      the whole of the heterohexameric complex by X-ray crystallography and
      conventional cryo-EM produced limited success. Modern cryo-EM technology ushered
      in a new era of structural biology that allowed the determination of the
      structure of the inactive double hexamer at an unprecedented resolution of 3.8 A.
      This review will focus on the fine details observed in the Mcm2-7 double
      hexameric complex and their implications for the function of the Mcm2-7 hexamer
      in its different roles during DNA replication.

PMID- 29357061
TI  - Replication Domains: Genome Compartmentalization into Functional Replication
      Units.
AB  - DNA replication occurs in a defined temporal order during S phase, known as the
      replication timing programme, which is regulated not only during the cell cycle
      but also during the process of development and differentiation. The units of
      replication timing regulation, known as replication domains (RDs), frequently
      comprise several nearly synchronously firing replication origins. Replication
      domains correspond to topologically associating domains (TADs) mapped by
      chromatin conformation capture methods and are likely to be the molecular
      equivalents of replication foci observed using cytogenetic methods. Both TAD and
      replication foci are considered to be stable structural units of chromosomes,
      conserved through the cell cycle and development, and accordingly, the boundaries
      of RDs also appear to be stable in different cell types. During both normal
      development and progression of disease, distinct cell states are characterized by
      unique replication timing signatures, with approximately half of genomic RDs
      switching replication timing between these cell states. Advances in functional
      genomics provide hope that we can soon gain an understanding of the cause and
      consequence of the replication timing programme and its myriad correlations with
      chromatin context and gene regulation.

PMID- 29357062
TI  - Rif1-Dependent Regulation of Genome Replication in Mammals.
AB  - Eukaryotic genomes are replicated starting from multiple origins of replication.
      Their usage is tightly regulated, and not all the potential origins are activated
      during a single cell cycle. In addition, the ones that are activated are
      activated in a sequential order. Why don't origins of replication normally all
      fire together? Is this important? And if so, why? Would any order of firing do,
      or does the specific sequence matter? How is this process regulated? These
      questions concern all eukaryotes but have proven extremely hard to address
      because replication timing is a process intricately connected with multiple
      aspects of nuclear function.

PMID- 29357063
TI  - G-Quadruplexes and DNA Replication Origins.
AB  - DNA replication ensures the accurate duplication of the genome at each cell
      cycle. During S phase, tens of thousands of replication origins throughout the
      vertebrate genome are activated according to a spatiotemporal program. The genome
      wide mapping of origins in several model systems has identified G-quadruplexes
      higher-order DNA structures formed from G-rich sequences-as potential key
      regulators of origin activity. Here, I describe genetic experiments demonstrating
      the role of G-quadruplexes in origin function. I discuss the different means by
      which G-quadruplexes might regulate origin function. Finally, comparisons of
      replicon organization in the three domains of life suggest that G-quadruplexes
      may have retained a conserved role in origin function during evolution.

PMID- 29357060
TI  - Architecture of the Saccharomyces cerevisiae Replisome.
AB  - Eukaryotic replication proteins are highly conserved, and thus study of
      Saccharomyces cerevisiae replication can inform about this central process in
      higher eukaryotes including humans. The S. cerevisiae replisome is a large and
      dynamic assembly comprised of ~50 proteins. The core of the replisome is composed
      of 31 different proteins including the 11-subunit CMG helicase; RFC clamp loader
      pentamer; PCNA clamp; the heteroligomeric DNA polymerases epsilon, delta, and
      alpha-primase; and the RPA heterotrimeric single strand binding protein. Many
      additional protein factors either travel with or transiently associate with these
      replisome proteins at particular times during replication. In this chapter, we
      summarize several recent structural studies on the S. cerevisiae replisome and
      its subassemblies using single particle electron microscopy and X-ray
      crystallography. These recent structural studies have outlined the overall
      architecture of a core replisome subassembly and shed new light on the mechanism
      of eukaryotic replication.

PMID- 29357064
TI  - Interaction of Rif1 Protein with G-Quadruplex in Control of Chromosome
      Transactions.
AB  - Recent studies on G-quadruplex (G4) revealed crucial and conserved functions of
      G4 in various biological systems. We recently showed that Rif1, a conserved
      nuclear factor, binds to G4 present in the intergenic regions and plays a major
      role in spatiotemporal regulation of DNA replication. Rif1 may tether chromatin
      fibers through binding to G4, generating specific chromatin domains that dictate
      the replication timing. G4 and its various binding partners are now implicated in
      many other chromosome regulations, including transcription, replication
      initiation, recombination, gene rearrangement, and transposition.

PMID- 29357065
TI  - Chromatin Replication and Histone Dynamics.
AB  - Inheritance of the DNA sequence and its proper organization into chromatin is
      fundamental for genome stability and function. Therefore, how specific chromatin
      structures are restored on newly synthesized DNA and transmitted through cell
      division remains a central question to understand cell fate choices and self
      renewal. Propagation of genetic information and chromatin-based information in
      cycling cells entails genome-wide disruption and restoration of chromatin,
      coupled with faithful replication of DNA. In this chapter, we describe how cells
      duplicate the genome while maintaining its proper organization into chromatin. We
      reveal how specialized replication-coupled mechanisms rapidly assemble newly
      synthesized DNA into nucleosomes, while the complete restoration of chromatin
      organization including histone marks is a continuous process taking place
      throughout the cell cycle. Because failure to reassemble nucleosomes at
      replication forks blocks DNA replication progression in higher eukaryotes and
      leads to genomic instability, we further underline the importance of the
      mechanistic link between DNA replication and chromatin duplication.

PMID- 29357067
TI  - Roles of SUMO in Replication Initiation, Progression, and Termination.
AB  - Accurate genome duplication during cell division is essential for life. This
      process is accomplished by the close collaboration between replication factors
      and many additional proteins that provide assistant roles. Replication factors
      establish the replication machineries capable of copying billions of nucleotides,
      while regulatory proteins help to achieve accuracy and efficiency of replication.
      Among regulatory proteins, protein modification enzymes can bestow fast and
      reversible changes to many targets, leading to coordinated effects on
      replication. Recent studies have begun to elucidate how one type of protein
      modification, sumoylation, can modify replication proteins and regulate genome
      duplication through multiple mechanisms. This chapter summarizes these new
      findings, and how they can integrate with the known regulatory circuitries of
      replication. As this area of research is still at its infancy, many outstanding
      questions remain to be explored, and we discuss these issues in light of the new
      advances.

PMID- 29357068
TI  - The Multiple Roles of Ubiquitylation in Regulating Challenged DNA Replication.
AB  - DNA replication is essential for the propagation of life and the development of
      complex organisms. However, replication is a risky process as it can lead to
      mutations and chromosomal alterations. Conditions challenging DNA synthesis by
      replicative polymerases or DNA helix unwinding, generally termed as replication
      stress, can halt replication fork progression. Stalled replication forks are
      unstable, and mechanisms exist to protect their integrity, which promote an
      efficient restart of DNA synthesis and counteract fork collapse characterized by
      the accumulation of DNA lesions and mutagenic events. DNA replication is a highly
      regulated process, and several mechanisms control replication timing and
      integrity both during unperturbed cell cycles and in response to replication
      stress. Work over the last two decades has revealed that key steps of DNA
      replication are controlled by conjugation of the small peptide ubiquitin. While
      ubiquitylation was traditionally linked to protein degradation, the complexity
      and flexibility of the ubiquitin system in regulating protein function have
      recently emerged. Here we review the multiple roles exerted by ubiquitin
      conjugating enzymes and ubiquitin-specific proteases, as well as readers of
      ubiquitin chains, in the control of eukaryotic DNA replication and replication
      coupled DNA damage tolerance and repair.

PMID- 29357066
TI  - The Temporal Regulation of S Phase Proteins During G1.
AB  - Successful DNA replication requires intimate coordination with cell-cycle
      progression. Prior to DNA replication initiation in S phase, a series of
      essential preparatory events in G1 phase ensures timely, complete, and precise
      genome duplication. Among the essential molecular processes are regulated
      transcriptional upregulation of genes that encode replication proteins,
      appropriate post-transcriptional control of replication factor abundance and
      activity, and assembly of DNA-loaded protein complexes to license replication
      origins. In this chapter we describe these critical G1 events necessary for DNA
      replication and their regulation in the context of both cell-cycle entry and cell
      cycle progression.

PMID- 29357070
TI  - Coordinating Replication with Transcription.
AB  - DNA topological transitions occur when replication forks encounter other DNA
      transactions such as transcription. Failure in resolving such conflicts leads to
      generation of aberrant replication and transcription intermediates that might
      have adverse effects on genome stability. Cells have evolved numerous
      surveillance mechanisms to avoid, tolerate, and resolve such replication
      transcription conflicts. Defects or non-coordination in such cellular mechanisms
      might have catastrophic effect on cell viability. In this chapter, we review
      consequences of replication encounters with transcription and its associated
      events, topological challenges, and how these inevitable conflicts alter the
      genome structure and functions.

PMID- 29357072
TI  - Cyclin E Deregulation and Genomic Instability.
AB  - Precise replication of genetic material and its equal distribution to daughter
      cells are essential to maintain genome stability. In eukaryotes, chromosome
      replication and segregation are temporally uncoupled, occurring in distinct
      intervals of the cell cycle, S and M phases, respectively. Cyclin E accumulates
      at the G1/S transition, where it promotes S phase entry and progression by
      binding to and activating CDK2. Several lines of evidence from different models
      indicate that cyclin E/CDK2 deregulation causes replication stress in S phase and
      chromosome segregation errors in M phase, leading to genomic instability and
      cancer. In this chapter, we will discuss the main findings that link cyclin
      E/CDK2 deregulation to genomic instability and the molecular mechanisms by which
      cyclin E/CDK2 induces replication stress and chromosome aberrations during
      carcinogenesis.

PMID- 29357073
TI  - Replication Through Repetitive DNA Elements and Their Role in Human Diseases.
AB  - Human cells contain various repetitive DNA sequences, which can be a challenge
      for the DNA replication machinery to travel through and replicate correctly.
      Repetitive DNA sequence can adopt non-B DNA structures, which could block the DNA
      replication. Prolonged stalling of the replication fork at the endogenous repeats
      in human cells can have severe consequences such as genome instability that
      includes repeat expansions, contractions, and chromosome fragility. Several
      neurological and muscular diseases are caused by a repeat expansion. Furthermore
      genome instability is the major cause of cancer. This chapter describes some of
      the important classes of repetitive DNA sequences in the mammalian genome, their
      ability to form secondary DNA structures, their contribution to replication fork
      stalling, and models for repeat expansion as well as chromosomal fragility.
      Included in this chapter are also some of the strategies currently employed to
      detect changes in DNA replication and proteins that could prevent the repeat
      mediated disruption of DNA replication in human cells. Additionally summarized
      are the consequences of repeat-associated perturbation of the DNA replication,
      which could lead to specific human diseases.

PMID- 29357074
TI  - Emicizumab-kxwh: First Global Approval.
AB  - Emicizumab-kxwh (Hemlibra(r)) is a bispecific humanized monoclonal antibody that
      restores the function of missing activated FVIII by bridging activated FIX and FX
      to facilitate effective haemostasis in patients with haemophilia A. Subcutaneous
      emicizumab-kxwh is approved in the USA for use as routine prophylaxis to prevent
      or reduce the frequency of bleeding episodes in adults and paediatric patients
      with haemophilia A (congenital FVIII deficiency) with FVIII inhibitors.
      Subcutaneous emicizumab-kxwh is awaiting approval in several countries worldwide,
      including in the EU and Japan, and is undergoing phase 3 development in
      haemophilia A without FVIII inhibitors. This article summarizes the milestones in
      the development of emicizumab-kxwh leading to its first global approval for use
      as prophylaxis to prevent or reduce the frequency of bleeding episodes in
      patients with haemophilia A.

PMID- 29357069
TI  - Regulation of Mammalian DNA Replication via the Ubiquitin-Proteasome System.
AB  - Proper regulation of DNA replication ensures the faithful transmission of genetic
      material essential for optimal cellular and organismal physiology. Central to
      this regulation is the activity of a set of enzymes that induce or reverse
      posttranslational modifications of various proteins critical for the initiation,
      progression, and termination of DNA replication. This is particularly important
      when DNA replication proceeds in cancer cells with elevated rates of genomic
      instability and increased proliferative capacities. Here, we describe how DNA
      replication in mammalian cells is regulated via the activity of the ubiquitin
      proteasome system as well as the consequence of derailed ubiquitylation signaling
      involved in this important cellular activity.

PMID- 29357076
TI  - A grey DEMATEL-based approach for modeling enablers of green innovation in
      manufacturing organizations.
AB  - Incorporating green practices into the manufacturing process has gained momentum
      over the past few years and is a matter of great concern for both manufacturers
      as well as researchers. Regulatory pressures in developed countries have forced
      the organizations to adopt green practices; however, this issue still lacks
      attention in developing economies like India. There is an urgent need to identify
      enablers of green innovation for manufacturing organizations and also to identify
      prominent enablers among those. This study is an attempt to first identify
      enablers of green innovation and then establish a causal relationship among them
      to identify the enablers that can drive others. Grey DEMATEL (Decision Making
      Trial and Evaluation Laboratory) methodology is used for establishing the causal
      relationship among enablers. The novelty of this study lies in the fact that no
      study has been done in the past to identify the enablers of green innovation and
      then establishing the causal relationship among them. A total of 21 enablers of
      green innovation have been identified; research indicates developing green
      manufacturing capabilities, resources for green innovation, ease of getting loans
      from financial institutions, and environmental regulations as the most
      influential enablers of green innovation. Managerial and practical implications
      of the research are also presented to assist managers of the case company in
      adopting green innovation practices at their end.

PMID- 29357075
TI  - Bacterial community structure and abundances of antibiotic resistance genes in
      heavy metals contaminated agricultural soil.
AB  - Soil contamination with heavy metals is a worldwide problem especially in China.
      The interrelation of soil bacterial community structure, antibiotic resistance
      genes, and heavy metal contamination in soil is still unclear. Here, seven
      agricultural areas (G1-G7) with heavy metal contamination were sampled with
      different distances (741 to 2556 m) to the factory. Denaturing gradient gel
      electrophoresis (DGGE) and Shannon index were used to analyze bacterial community
      diversity. Real-time fluorescence quantitative PCR was used to detect the
      relative abundance of ARGs sul1, sul2, tetA, tetM, tetW, one mobile genetic
      elements (MGE) inti1. Results showed that all samples were polluted by Cadmium
      (Cd), and some of them were polluted by lead (Pb), mercury (Hg), arsenic (As),
      copper (Cu), and zinc (Zn). DGGE showed that the most abundant bacterial species
      were found in G7 with the lightest heavy metal contamination. The results of the
      principal component analysis and clustering analysis both showed that G7 could
      not be classified with other samples. The relative abundance of sul1 was
      correlated with Cu, Zn concentration. Gene sul2 are positively related with total
      phosphorus, and tetM was associated with organic matter. Total gene abundances
      and relative abundance of inti1 both correlated with organic matter. Redundancy
      analysis showed that Zn and sul2 were significantly related with bacterial
      community structure. Together, our results indicate a complex linkage between
      soil heavy metal concentration, bacterial community composition, and some global
      disseminated ARG abundance.

PMID- 29357071
TI  - Fragility Extraordinaire: Unsolved Mysteries of Chromosome Fragile Sites.
AB  - Chromosome fragile sites are a fascinating cytogenetic phenomenon now widely
      implicated in a slew of human diseases ranging from neurological disorders to
      cancer. Yet, the paths leading to these revelations were far from direct, and the
      number of fragile sites that have been molecularly cloned with known disease
      associated genes remains modest. Moreover, as more fragile sites were being
      discovered, research interests in some of the earliest discovered fragile sites
      ebbed away, leaving a number of unsolved mysteries in chromosome biology. In this
      review we attempt to recount some of the early discoveries of fragile sites and
      highlight those phenomena that have eluded intense scrutiny but remain extremely
      relevant in our understanding of the mechanisms of chromosome fragility. We then
      survey the literature for disease association for a comprehensive list of fragile
      sites. We also review recent studies addressing the underlying cause of
      chromosome fragility while highlighting some ongoing debates. We report an
      observed enrichment for R-loop forming sequences in fragile site-associated genes
      than genomic average. Finally, we will leave the reader with some lingering
      questions to provoke discussion and inspire further scientific inquiries.

PMID- 29357077
TI  - Does finance affect environmental degradation: evidence from One Belt and One
      Road Initiative region?
AB  - This paper explores the effects of finance on environmental degradation and
      investigates environmental Kuznets curve (EKC) of each country among 52 that
      participate in the One Belt and One Road Initiative (OBORI) using the latest long
      panel data span (1980-2016). We utilized panel long run econometric models (fully
      modified ordinary least square and dynamic ordinary least square) to explore the
      long-run estimates in full panel and country level. Moreover, the Dumitrescu and
      Hurlin (2012) causality test is applied to examine the short-run causalities
      among our considered variables. The empirical findings validate the EKC
      hypothesis; the long-run estimates point out that finance significantly enhances
      the environmental degradation (negatively in few cases). The short-run
      heterogeneous causality confirms the bi-directional causality between finance and
      environmental degradation. The empirical outcomes suggest that policymakers
      should consider the environmental degradation issue caused by financial
      development in the One Belt and One Road region.

PMID- 29357078
TI  - Risk approximation in decision making: approximative numeric abilities predict
      advantageous decisions under objective risk.
AB  - Many decision situations in everyday life involve mathematical considerations. In
      decisions under objective risk, i.e., when explicit numeric information is
      available, executive functions and abilities to handle exact numbers and ratios
      are predictors of objectively advantageous choices. Although still debated, exact
      numeric abilities, e.g., normative calculation skills, are assumed to be related
      to approximate number processing skills. The current study investigates the
      effects of approximative numeric abilities on decision making under objective
      risk. Participants (N = 153) performed a paradigm measuring number-comparison,
      quantity-estimation, risk-estimation, and decision-making skills on the basis of
      rapid dot comparisons. Additionally, a risky decision-making task with exact
      numeric information was administered, as well as tasks measuring executive
      functions and exact numeric abilities, e.g., mental calculation and ratio
      processing skills, were conducted. Approximative numeric abilities significantly
      predicted advantageous decision making, even beyond the effects of executive
      functions and exact numeric skills. Especially being able to make accurate risk
      estimations seemed to contribute to superior choices. We recommend approximation
      skills and approximate number processing to be subject of future investigations
      on decision making under risk.

PMID- 29357079
TI  - Pharmacokinetics, pharmacodynamics, safety, and tolerability of intravenous
      ferric carboxymaltose: a dose-escalation study in Japanese volunteers with iron
      deficiency anemia.
AB  - Iron-deficiency anemia (IDA) is the most common form of anemia. Iron replacement
      therapy is an effective treatment, but oral and previously available intravenous
      (IV) formulations in Japan have disadvantages such as side effects, immunogenic
      reactions, low dose per tablet/vial, and the need for continuous administration.
      Ferric carboxymaltose (FCM), which overcomes these limitations, is widely used as
      an IV iron preparation outside of Japan. In this single-center, open-label,
      single-dose escalation study, we investigated the pharmacokinetics (PK),
      pharmacodynamics (PD), safety, and tolerability of FCM in Japanese subjects.
      Twenty-four Japanese IDA patients, diagnosed by hemoglobin, serum ferritin, and
      transferrin saturation, were assigned in equal groups to the 100, 500, 800, and
      1000 mg iron dose arms. All subjects completed the study without important
      protocol deviations. Mean total serum iron concentrations showed a rapid, dose
      dependent increase after FCM injection, reaching a maximum within 1 h. Mean
      reticulocyte counts significantly increased in all arms, suggesting improved
      hematopoietic function. Fourteen of 24 subjects experienced adverse events, but
      these were neither serious nor led to drug interruption. The PK/PD and safety
      profiles were similar in Japanese and European subjects. Ferric carboxymaltose is
      safe for administration in Japanese patients with IDA.

PMID- 29357080
TI  - Lymphoma epidemiology in Korea and the real clinical field including the
      Consortium for Improving Survival of Lymphoma (CISL) trial.
AB  - Lymphomas are a heterogeneous group of disease entities with well-defined
      clinical, morphological, immunophenotypic, and cytogenetic characteristics.
      Moreover, regional and racial differences have been reported in their incidence
      and subtype compositions. Here, we reviewed the epidemiology of lymphomas and
      summarized the recent achievements in specific subtypes prevalent in Korean
      population, focusing on clinical studies conducted by the Consortium for
      Improving Survival of Lymphoma (CISL) of the Korean Society of Hematology
      Lymphoma Working Party (KSH-LWP).

PMID- 29357081
TI  - Biochemical efficacy of long-acting lanreotide depot/Autogel in patients with
      acromegaly naive to somatostatin-receptor ligands: analysis of three multicenter
      clinical trials.
AB  - PURPOSE: In clinical research involving acromegalic patients naive to
      somatostatin-receptor ligands (SRLs), 19 and 31% of those receiving the SRLs
      octreotide LAR and pasireotide LAR, respectively, achieved GH < 2.5 ng/mL +
      normalized IGF-1 concentrations. The proportions achieving control appeared
      higher in the post-surgery compared with the de-novo setting with pasireotide,
      but more similar with octreotide. Using pooled data from multicenter clinical
      trials, we examined the biochemical efficacy of lanreotide depot/Autogel in
      similar settings. METHODS: Inclusion criteria: Ipsen-sponsored, 48-52-week trials
      in SRL-naive acromegalic populations receiving lanreotide depot (60-120 mg);
      patients were included if de novo (no prior acromegaly treatment) or post-surgery
      (no medical treatment; radiotherapy allowed unless within previous 3 years).
      Efficacy endpoints included normalized IGF-1 levels and GH < 2.5 ng/mL +
      normalized IGF-1 at study end/last value available. ANALYSES: all patients
      (analysis #1) and subset with baseline GH > 5 ng/mL (analysis #2). RESULTS: Three
      studies were included. Analysis #1: normalized IGF-1 was achieved by 42% (71/171)
      of patients overall (post-surgery, 46% [21/46]; de-novo, 40% [50/125]); GH < 2.5
      ng/mL + normalized IGF-1 was achieved by 35% (59/171) (39% [18/46] and 33%
      [41/125], respectively). Analysis #2: normalized IGF-1 levels, 39% (46/118) (post
      surgery, 40% [10/25]; de-novo, 39% [36/93]); GH < 2.5 ng/mL + normalized IGF-1,
      31% (36/118) (28% [7/25] and 31% [29/93], respectively). CONCLUSION: In these
      pooled analyses of SRL-naive patients receiving lanreotide depot, 39-42% achieved
      IGF-1 control and 31-35% achieved GH and IGF-1 control. Control rates within post
      surgery cohorts did not differ markedly from those in corresponding de-novo
      cohorts.

PMID- 29357082
TI  - Testicular germ line cell identification, isolation, and transplantation in two
      North American catfish species.
AB  - Our aim was to transplant blue catfish germ line stem cells into blastulae of
      triploid channel catfish embryos to produce interspecific xenogenic catfish. The
      morphological structure of the gonads of blue catfish (Ictalurus furcatus) in ~
      90- to 100-day-old juveniles, two-year-old juveniles, and mature adults was
      studied histologically. Both oogonia (12-15 MUm, diameter with distinct nucleus 7
      8 MUm diameter) and spermatogonia (12-15 MUm, with distinct nucleus 6-7.5 MUm
      diameter) were found in all ages of fish. The percentage of germ line stem cells
      was higher in younger blue catfish of both sexes. After the testicular tissue was
      trypsinized, a discontinuous density gradient centrifugation was performed using
      70, 45, and 35% Percoll to enrich the percentage of spermatogonial stem cells
      (SSCs). Four distinct cell bands were generated after the centrifugation. It was
      estimated that 50% of the total cells in the top band were type A spermatogonia
      (diameter 12-15 MUm) and type B spermatogonia (diameter 10-11 MUm). Germ cells
      were confirmed with expression of vasa. Blastula-stage embryos of channel catfish
      (I. punctatus) were injected with freshly dissociated blue catfish testicular
      germ cells as donor cells for transplantation. Seventeen days after the
      transplantation, 33.3% of the triploid channel catfish fry were determined to be
      xenogenic catfish. This transplantation technique was efficient, and these
      xenogenic channel catfish need to be grown to maturity to verify their
      reproductive capacity and to verify that for the first time SSCs injected into
      blastulae were able to migrate to the genital ridge and colonize. These results
      open the possibility of artificially producing xenogenic channel catfish males
      that can produce blue catfish sperm and mate with normal channel catfish females
      naturally. The progeny would be all C * B hybrid catfish, and the efficiency of
      hybrid catfish production could be improved tremendously in the catfish industry.

PMID- 29357083
TI  - Gastrointestinal Tract Pathology in a BALB/c Niemann-Pick Disease Type C1 Null
      Mouse Model.
AB  - BACKGROUND: Niemann-Pick disease, type C (NPC) is a rare lysosomal storage
      disorder characterized by progressive neurodegeneration, splenomegaly,
      hepatomegaly, and early death. NPC is caused by mutations in either the NPC1 or
      NPC2 gene. Impaired NPC function leads to defective intracellular transport of
      unesterified cholesterol and its accumulation in late endosomes and lysosomes. A
      high frequency of Crohn disease has been reported in NPC1 patients, suggesting
      that gastrointestinal tract pathology may become a more prominent clinical issue
      if effective therapies are developed to slow the neurodegeneration. The Npc1 nih
      mouse model on a BALB/c background replicates the hepatic and neurological
      disease observed in NPC1 patients. Thus, we sought to characterize the
      gastrointestinal tract pathology in this model to determine whether it can serve
      as a model of Crohn disease in NPC1. METHODS: We analyzed the gastrointestinal
      tract and isolated macrophages of BALB/cJ cNctr-Npc1m1N/J (Npc1-/-) mouse model
      to determine whether there was any Crohn-like pathology or inflammatory cell
      activation. We also evaluated temporal changes in the microbiota by 16S rRNA
      sequencing of fecal samples to determine whether there were changes consistent
      with Crohn disease. RESULTS: Relative to controls, Npc1 mutant mice demonstrate
      increased inflammation and crypt abscesses in the gastrointestinal tract;
      however, the observed pathological changes are significantly less than those
      observed in other Crohn disease mouse models. Analysis of Npc1 mutant macrophages
      demonstrated an increased response to lipopolysaccharides and delayed
      bactericidal activity; both of which are pathological features of Crohn disease.
      Analysis of the bacterial microbiota does not mimic what is reported in Crohn
      disease in either human or mouse models. We did observe significant increases in
      cyanobacteria and epsilon-proteobacteria. The increase in epsilon-proteobacteria
      may be related to altered cholesterol homeostasis since cholesterol is known to
      promote growth of this bacterial subgroup. CONCLUSIONS: Macrophage dysfunction in
      the BALB/c Npc1-/- mouse is similar to that observed in other Crohn disease
      models. However, neither the degree of pathology nor the microbiota changes are
      typical of Crohn disease. Thus, this mouse model is not a good model system for
      Crohn disease pathology reported in NPC1 patients.

PMID- 29357084
TI  - Risk Factors for Hidradenitis Suppurativa in Patients with Inflammatory Bowel
      Disease.
AB  - BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder
      characterized by recurrent nodules, abscesses, and sinus tracts that can be
      debilitating and significantly impair quality of life. Small studies and case
      reports have suggested a possible association between HS and inflammatory bowel
      disease (IBD). AIMS: We performed a case-control study to further characterize
      IBD patients with HS in terms of smoking status, BMI, sites affected by HS, IBD
      type and features, and IBD medication history. METHODS: A total of 38 patients
      with HS and IBD were identified and matched on age, gender, and IBD type to 136
      controls with IBD but not HS. Clinical characteristics of interest were obtained
      through extensive review of the electronic health record. RESULTS: Among patients
      with HS and IBD, the most common sites affected by HS were the inguinal,
      perianal, and axillary regions. Relative to patients with IBD alone, patients
      with HS and IBD were nearly six times more likely to be current smokers (p <
      0.01) and nearly 11 times more likely to be obese (p < 0.01). Patients with HS
      and Crohn's were significantly more likely to have ileocolonic and perianal
      disease than patients with CD only (OR 8.31, 95% CI 2.90-23.80 and OR 2.85, 95%
      CI 1.19-6.81, respectively; p < 0.01 for both). CONCLUSIONS: Relative to patients
      with IBD who do not develop HS, patients with IBD and HS are more likely to be
      overweight or obese, to be former or current smokers, and to have ileocolonic
      and/or perianal disease.

PMID- 29357085
TI  - High-flow arteriovenous fistula and heart failure: could the indexation of blood
      flow rate and echocardiography have a role in the identification of patients at
      higher risk?
AB  - BACKGROUND: Although only high-flow arteriovenous fistulas (AVFs) are postulated
      to cause high-output cardiac failure (HOCF), there are currently no universally
      accepted criteria defining a high-flow fistula. METHODS: To verify if vascular
      access blood flow (Qa) >= 2000 ml/min provides an accurate definition of high
      flow fistula, we selected 29 consecutive patients with Qa >= 2000 ml/min at color
      duplex ultrasound examination and assessed them for the presence of cardiac
      failure symptoms; transthoracic echocardiography was also performed. RESULTS:
      Nineteen patients (65%) had heart failure symptoms and were classified with HOCF.
      At receiver operating characteristic (ROC) curve analysis, Qa ml/min values did
      not identify patients with heart failure symptoms but when AVF blood flow was
      indexed for height2.7, Qa >= 603 ml/min/m2.7 detected the occurrence of HOCF with
      good accuracy (sensitivity 100%, specificity 60%, efficiency 86%, positive
      predictive value 83%, negative predictive value 100%, area under curve 0.75). At
      echocardiographic evaluation, patients with Qa >= 603 ml/min/m2.7 had a more
      severe increase of left ventricular mass (63 +/- 18 vs. 47 +/- 7 g/m2.7, p <
      0.003), left ventricular diastolic volume (140 +/- 42 vs. 109 +/- 14 ml, p <
      0.007), left atrial volume (53 +/- 23 vs. 39 +/- 5 ml/m2, p < 0.015), a higher
      incidence of diastolic dysfunction (70 vs. 17%, p < 0.019) and higher CO
      reduction after AVF manual compression (2151 +/- 875 vs. 1292 +/- 527 ml/min, p <
      0.009) than patients with Qa < 603 ml/min/m2.7. CONCLUSIONS: Indexation of AVF
      blood flow should be considered in defining high-flow fistula because the effect
      of Qa may differ in individuals of different sizes. A Qa value >= 603 ml/min/m2.7
      and its association with some echocardiographic alterations could identify
      patients at higher risk for HOCF.

PMID- 29357087
TI  - A novel de novo mutation of ACTG1 in two sporadic non-syndromic hearing loss
      cases.

PMID- 29357086
TI  - Photoinhibition of photosystem I in Nephrolepis falciformis depends on reactive
      oxygen species generated in the chloroplast stroma.
AB  - We studied how high light causes photoinhibition of photosystem I (PSI) in the
      shade-demanding fern Nephrolepis falciformis, in an attempt to understand the
      mechanism of PSI photoinhibition under natural field conditions. Intact leaves
      were treated with constant high light and fluctuating light. Detached leaves were
      treated with constant high light in the presence and absence of methyl viologen
      (MV). Chlorophyll fluorescence and P700 signal were determined to estimate
      photoinhibition. PSI was highly oxidized under high light before treatments. N.
      falciformis showed significantly stronger photoinhibition of PSI and PSII under
      constant high light than fluctuating light. These results suggest that high
      levels of P700 oxidation ratio cannot prevent PSI photoinhibition under high
      light in N. falciformis. Furthermore, photoinhibition of PSI in N. falciformis
      was largely accelerated in the presence of MV that promotes the production of
      superoxide anion radicals in the chloroplast stroma by accepting electrons from
      PSI. From these results, we propose that photoinhibition of PSI in N. falciformis
      is mainly caused by superoxide radicals generated in the chloroplast stroma,
      which is different from the mechanism of PSI photoinhibition in Arabidopsis
      thaliana and spinach. Here, we provide some new insights into the PSI
      photoinhibition under natural field conditions.

PMID- 29357088
TI  - Intermittent nocturnal hypoxia and metabolic risk in obese adolescents with
      obstructive sleep apnea.
AB  - PURPOSE: There is conflicting data regarding the independent associations of
      obstructive sleep apnea (OSA) with metabolic risk in obese youth. Previous
      studies have not consistently addressed central adiposity, specifically elevated
      waist to height ratio (WHtR), which is associated with metabolic risk independent
      of body mass index. OBJECTIVE: The objective of this study was to determine the
      independent effects of the obstructive apnea-hypopnea index (OAHI) and associated
      indices of nocturnal hypoxia on metabolic function in obese youth after adjusting
      for WHtR. METHODS: Subjects had standardized anthropometric measurements. Fasting
      blood included insulin, glucose, glycated hemoglobin, alanine transferase, and
      aspartate transaminase. Insulin resistance was quantified with the homeostatic
      model assessment. Overnight polysomnography determined the OAHI and nocturnal
      oxygenation indices. RESULTS: Of the 75 recruited subjects, 23% were diagnosed
      with OSA. Adjusting for age, gender, and WHtR in multivariable linear regression
      models, a higher oxygen desaturation index was associated with a higher fasting
      insulin (coefficient [standard error] = 48.076 [11.255], p < 0.001), higher
      glycated hemoglobin (coefficient [standard error] = 0.097 [0.041], p = 0.02),
      higher insulin resistance (coefficient [standard error] = 1.516 [0.364], p <
      0.001), elevated alanine transferase (coefficient [standard error] = 11.631
      [2.770], p < 0.001), and aspartate transaminase (coefficient [standard error] =
      4.880 [1.444], p = 0.001). However, there were no significant associations
      between OAHI, glucose metabolism, and liver enzymes. CONCLUSION: Intermittent
      nocturnal hypoxia rather than the OAHI was associated with metabolic risk in
      obese youth after adjusting for WHtR. Measures of abdominal adiposity such as
      WHtR should be considered in future studies that evaluate the impact of OSA on
      metabolic health.

PMID- 29357089
TI  - Therapeutic efficacy of a synthetic epsin mimetic peptide in glioma tumor model:
      uncovering multiple mechanisms beyond the VEGF-associated tumor angiogenesis.
AB  - Binding of epsin ubiquitin-interacting motif (UIM) with ubiquitylated VEGFR2 is a
      critical mechanism for epsin-dependent VEGFR2 endocytosis and physiological
      angiogenesis. Deletion of epsins in vessel endothelium produces uncontrolled
      tumor angiogenesis and retards tumor growth in animal models. The aim of this
      study is to test the therapeutic efficacy and targeting specificity of a
      chemically-synthesized peptide, UPI, which compete for epsin binding sites in
      VEGFR2 and potentially inhibits Epsin-VEGFR2 interaction in vivo, in an attempt
      to reproduce an epsin-deficient phenotype in tumor angiogenesis. Our data show
      that UPI treatment significantly inhibits and shrinks tumor growth in GL261
      glioma tumor model. UPI peptide specifically targets VEGFR2 signaling pathway
      revealed by genetic and biochemical approaches. Furthermore, we demonstrated that
      UPI peptide treatment caused serious thrombosis in tumor vessels and damages
      tumor cells after a long-term UPI peptide administration. Besides, we revealed
      that UPI peptides were unexpectedly targeted cancer cells and induced apoptosis.
      We conclude that UPI peptide is a potent inhibitor to glioma tumor growth through
      specific targeting of VEGFR2 signaling in the tumor vasculature and cancer cells,
      which may offer a potentially novel treatment for cancer patients who are
      resistant to current anti-VEGF therapies.

PMID- 29357090
TI  - Biomimetic brain tumor niche regulates glioblastoma cells towards a cancer stem
      cell phenotype.
AB  - Glioblastoma (GBM) is the most malignant primary brain tumor and contains
      tumorigenic cancer stem cells (CSCs), which support the progression of tumor
      growth. The selection of CSCs and facilitation of the brain tumor niches may
      assist the development of novel therapeutics for GBM. Herein, hydrogel materials
      composed of agarose and hydroxypropyl methyl cellulose (HMC) in different
      concentrations were established and compared to emulate brain tumor niches and
      CSC microenvironments within a label-free system. Human GBM cell line, U-87 MG,
      was cultured on a series of HMC-agarose based culture system. Cell aggregation
      and spheroids formation were investigated after 4 days of culture, and 2.5% HMC
      agarose based culture system demonstrated the largest spheroids number and size.
      Moreover, CD133 marker expression of GBM cells after 6 days of culture in 2.5%
      HMC-agarose based culture system was 60%, relatively higher than the control
      group at only 15%. Additionally, cells on 2.5% HMC-agarose based culture system
      show the highest chemoresistance, even at the high dose of 500 uM temozolomide
      for 72 h, the live cell ratio was still > 80%. Furthermore, the results also
      indicate that the expression of ABCG2 gene was up-regulated after culture in 2.5%
      HMC-agarose based culture system. Therefore, our results demonstrated that
      biomimetic brain tumor microenvironment may regulate GBM cells towards the CSC
      phenotype and expression of CSC characteristics. The microenvironment selection
      and spheroids formation in HMC-agarose based culture system may provide a label
      free CSC selection strategy and drug testing model for future biomedical
      applications.

PMID- 29357091
TI  - Chemical Profile of the Sulphated Saponins from the Starfish Luidia senegalensis
      Collected as by-Catch Fauna in Brazilian Coast.
AB  - The by-catch fauna of the shrimp fishery includes a number of marine
      invertebrates that are discarded because they do not have commercial value. In
      order to try to add some value to these materials, we analyzed the chemical
      composition of the starfish Luidia senegalensis collected in the Brazilian coast
      as a consequence of the trawling fishery method. In order to access their
      chemical composition, we used a combination of solid phase extraction (SPE)
      followed by ultra-high performance liquid chromatography coupled to electrospray
      ionization ion trap tandem mass spectrometry (UPLC-ESI-IT-MSn). Luidia
      senegalensis contains asterosaponins, which are sulphated glycosilated steroids,
      containing five and six sugar moieties, in addition to polyhydroxysteroids. This
      study helped us to support the presence of important and potentially bioactive
      compounds in invertebrates associated to the by-catch fauna of the shrimp
      fishery, using a fast and efficient method.

PMID- 29357092
TI  - Evaluation of Antimycobacterial Activity of Higenamine Using Galleria mellonella
      as an In Vivo Infection Model.
AB  - The Phytochemical investigation on MeOH extract on the bark of Aristolochia
      brasiliensis Mart. & Zucc (Aristolochiaceae) led to the isolation of major
      compound (1) as light brown grainy crystals. The compound was identified as 1-(4
      hydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline-6,7-diol (higenamine) on the basis
      of spectroscopic analysis, including 1D and 2D NMR spectroscopy. The compound was
      evaluated for its antimycobacterial activity against Mycobacterium indicus pranii
      (MIP), using Galleria mellonella larva as an in vivo infection model. The
      survival of MIP infected larvae after a single dose treatment of 100 mg/kg body
      weight of higenamine was 80% after 24 h. Quantitatively the compound exhibited a
      dose dependent activity, as evidenced by the reduction of colony density from 105
      to 103 CFU for test concentrations of 50, 100, 150 and 200 mg/kg body weight
      respectively. The IC50 value for higenamine was 161.6 mg/kg body weight as
      calculated from a calibration curve. Further analysis showed that, a complete
      inhibition of MIP in the G. mellonella could be achieved at 334 mg/kg body
      weight. Despite the fact that MIP has been found to be highly resistant against
      isoniazid (INH) in an in vitro assay model, in this study the microbe was highly
      susceptible to this standard anti-TB drug. The isolation of higenamine from the
      genus Aristolochia and the method used to evaluate its in vivo antimycobacterial
      activity in G. mellonella are herein reported for the first time.

PMID- 29357093
TI  - Atrial fibrillation diagnosed by a medical checkup is associated with a poor
      outcome of catheter ablation.
AB  - Atrial fibrillation (AF), especially asymptomatic cases, is often detected by
      medical checkups. We investigated the outcome of AF ablation in cases detected by
      medical checkups. We reviewed the data of 735 patients with AF (56 +/- 10 years,
      paroxysmal: 441 patients) who underwent initial catheter ablation. All patients
      were divided into two groups based on their AF being diagnosed either by a
      medical checkup (group M) or not (group NM). AF was diagnosed by medical checkups
      in 263 (36%) patients. In Group M, the age was younger, time from the diagnosis
      to ablation shorter, left atrium dimension larger, and left ventricular ejection
      fraction lower than in Group NM. Male gender, persistent AF, and asymptomatic AF
      were more frequently seen in Group M than in Group NM. A mean of 13 +/- 11 months
      after the initial ablation procedure, AF recurrence was more frequently observed
      in group M compared to group NM (P = 0.018). While the AF recurrence rate was
      similar in both groups in persistent AF patients (P = 0.87), it was more
      frequently observed in Group M than in Group NM in paroxysmal AF patients (P =
      0.005). AF diagnosed by medical checkups was often associated with a worse
      outcome of catheter ablation, especially in paroxysmal AF patients.

PMID- 29357094
TI  - Interatrial septal motion as a novel index to predict left atrial pressure.
AB  - We investigated whether the interatrial septal (IAS) motion of each heartbeat
      which is observed by transesophageal echocardiography reflects left atrial
      pressure (LAP) in patients with atrial fibrillation (AF). We studied 100 patients
      (70 males, age 67 +/- 9 years) who underwent catheter ablation for AF. The
      amplitude of IAS motion was measured using M-mode and averaged for five cardiac
      cycles. Left and right atrial pressures, the left to right atrial pressure
      gradient were directly measured during the catheter ablation. In patients with
      sinus rhythm during measurement, elevated mean LAP, larger maximum left to right
      atrial pressure gradient, and greater left atrial emptying fraction were
      associated with IAS motion. The optimal cut-off value of the IAS motion for
      predicting high LAP (mean LAP > 15 mmHg) was 8.5 mm (sensitivity 100%,
      specificity 70.1%) in patients with sinus rhythm during pressure measurement. In
      addition, all patients were divided into 6 groups based on rhythm during
      measurement and cutoff value of IAS motion. In patients with sinus rhythm during
      measurement, low IAS motion group had a highest prevalence of elevated LAP
      compared with high IAS motion group (64 vs. 0%, P < 0.0001). The amplitude of
      interatrial septal motion during sinus rhythm reflects left atrial pressure in
      patients with atrial fibrillation. Interatrial septal motion could be a new index
      to predict elevated left atrial pressure.

PMID- 29357095
TI  - Beneficial effects of adaptive servo-ventilation therapy on readmission and
      medical costs in patients with chronic heart failure.
AB  - Adaptive servo-ventilation (ASV) therapy is a novel modality of noninvasive
      positive pressure ventilation and is now widely utilized to treat patients with
      chronic heart failure (CHF). However, there has been no clinical study of the
      effect of ASV therapy on readmission and cost-effectiveness for the treatment of
      CHF. The present study was conducted to evaluate the clinical efficacy and cost
      effectiveness of home ASV therapy in 45 patients with a history of two or more
      admissions a year for worsening CHF. Seven patients refused to undergo chronic
      ASV therapy and three died. Thus, 35 patients were eventually enrolled in the
      present study. New York Heart Association class (2.8 +/- 0.4 versus 2.3 +/- 0.5,
      p < 0.001), log plasma B-type natriuretic peptide level (2.53 +/- 0.44 versus
      2.29 +/- 0.40 pg/mL, p < 0.0001), left atrial dimension (47.5 +/- 7.0 versus 44.9
      +/- 7.6 mm, p = 0.014), and mitral regurgitation area ratio (20.3 +/- 12.1 versus
      16.9 +/- 8.9%, p = 0.007) decreased significantly after 12 months of ASV therapy.
      The frequency of hospitalization after ASV was significantly lower than before
      ASV (1.0 +/- 1.0 versus 2.3 +/- 0.5 times/year/patient, p < 0.0001). ASV also
      decreased the duration of hospitalization from 64.4 +/- 46.5 to 22.8 +/- 27.5
      days/year/patient (p < 0.0001). Consequently, the total medical costs were
      reduced by 37% after ASV (1.95 +/- 1.37 versus 3.11 +/- 1.75 million yen/patient,
      p = 0.003). ASV therapy reduced readmissions and medical costs in patients with
      CHF.

PMID- 29357096
TI  - Associations Between Television Viewing and Adiposity Among South Asians.
AB  - OBJECTIVE: Sedentary behaviors related to television (TV) viewing are associated
      with adiposity; however, few investigations have focused on South Asians, an
      ethnicity particularly vulnerable to metabolic perturbations. This study examined
      the relationships between TV viewing and adiposity in a cohort of middle-aged and
      older South Asians. METHOD: Data were obtained from Mediators of Atherosclerosis
      in South Asians Living in America (MASALA) study (N = 906; mean age [standard
      deviation] = 55 [9.4] years, 46% women). TV viewing hours per week was assessed
      through questionnaire and classified into tertiles for analysis. Multivariate
      linear regression models were used to examine the associations between TV viewing
      and measures of adiposity and body composition including body mass index (BMI),
      waist circumference, pericardial fat volume, and visceral, subcutaneous, and
      inter-muscular fat area after adjusting for covariates including intentional
      exercise. RESULTS: Participants who were women, older, with lower education
      levels, and living longer in the United States watched TV for longer periods of
      times. Duration of TV viewing was positively associated with BMI (p < 0.001),
      waist circumference (p < 0.001), visceral fat area (p = 0.001), and pericardial
      fat volume (p = 0.003) independent of intentional exercise. CONCLUSIONS: While
      studies in South Asians with a longitudinal design need to confirm our findings,
      our cross-sectional results indicate that reduction in TV viewing may be
      beneficial in reducing adiposity and maintaining a healthy body composition.

PMID- 29357097
TI  - Health Insurance and the Aging: Evidence From the Seguro Popular Program in
      Mexico.
AB  - Aimed at covering the large fraction of workers in the informal sector without
      access to a social security program, the Mexican public health insurance program
      Seguro Popular began in 2002 and now reaches more than 50 million individuals. We
      estimate impacts of Seguro Popular for the population aged 50 and older on a set
      of indicators related to health care including utilization, diagnostic/preventive
      tests, and treatment conditional on being ill. Using the longitudinal Mexican
      Health and Aging Study over the period 2001-2012, we conduct before and after
      difference-in-difference matching impact estimators. Our results suggest large
      and important effects of the Program on utilization and diagnostic tests. We find
      overall smaller effects on the probability of being in treatment for individuals
      with chronic diseases, but these effects are concentrated in rural areas with
      relatively more health services versus rural areas with lower levels of health
      services. These results suggest that, to the extent that health services become
      more available in rural areas lacking services, effects of health insurance may
      increase.

PMID- 29357098
TI  - How We Fall Apart: Similarities of Human Aging in 10 European Countries.
AB  - We analyze human aging-understood as health deficit accumulation-for a panel of
      European individuals, using four waves of the Survey of Health, Aging and
      Retirement in Europe (SHARE data set) and constructing a health deficit index.
      Results from log-linear regressions suggest that, on average, elderly European
      men and women develop approximately 2.5 % more health deficits from one birthday
      to the next. In nonlinear regressions (akin to the Gompertz-Makeham model),
      however, we find much greater rates of aging and large differences between men
      and women as well as between countries. Interestingly, these differences follow a
      particular regularity (akin to the compensation effect of mortality) and suggest
      an age at which average health deficits converge for men and women and across
      countries. This age, which may be associated with human life span, is estimated
      as 102 +/- 2.6 years.

PMID- 29357099
TI  - Treatment of selective mutism: a 5-year follow-up study.
AB  - Selective mutism (SM) has been defined as an anxiety disorder in the diagnostic
      and statistical manual of mental disorders (DSM-5). Cognitive behavioral therapy
      (CBT) is the recommended approach for SM, but prospective long-term outcome
      studies are lacking. Reports from the children themselves, and the use of more
      global quality of life measures, are also missing in the literature. We have
      developed a school-based CBT intervention previously found to increase speech in
      a pilot efficacy study and a randomized controlled treatment study. Continued
      progress was found in our 1-year follow-up studies, where older age and more
      severe SM had a significant negative effect upon outcome. In the present study,
      we provide 5-year outcome data for 30 of these 32 children with SM who completed
      the same CBT for mean 21 weeks (sd 5, range 8-24) at mean age 6 years (10 boys).
      Mean age at the 5-year follow-up was 11 years (range 8-14). Outcome measures were
      diagnostic status, the teacher- and parent-rated selective mutism questionnaires,
      and child rated quality of life and speaking behavior. At the 5-year follow-up,
      21 children were in full remission, five were in partial remission and four
      fulfilled diagnostic criteria for SM. Seven children (23%) fulfilled criteria for
      social phobia, and separation anxiety disorder, specific phobia and/or enuresis
      nocturna were found in a total of five children (17%). Older age and severity at
      baseline and familial SM were significant negative predictors of outcome.
      Treatment gains were maintained on the teacher- and parent questionnaires. The
      children rated their overall quality of life as good. Although most of them
      talked outside of home, 50% still experienced it as somewhat challenging. These
      results point to the long-term effectiveness of CBT for SM, but also highlight
      the need to develop more effective interventions for the subset of children with
      persistent symptoms.Clinical trials registration NCT01002196.

PMID- 29357100
TI  - Autodisplay of an avidin with biotin-binding activity on the surface of
      Escherichia coli.
AB  - OBJECTIVES: To display a recombinant avidin fused to the autotransporter ShdA to
      bind biotinylated molecules on the surface of Escherichia coli. RESULTS: Two
      chimeric protein constructs containing avidin fused to the autotransporter ShdA
      were expressed on the surface of Escherichia coli DH5alpha. One fusion protein
      contained 476 amino acids of the ShdA alpha and beta domains, whereas the second
      consisted of a 314 amino acid from alpha and truncated beta domains. Protein
      production was verified by SDS-PAGE using an antibody to the molecular FLAG-tag.
      The surface display of the avidin-shdA fusion protein was confirmed by confocal
      microscopy and flow cytometry analysis, and the biotin-binding activity was
      evaluated by fluorescence microscopy and flow cytometry using biotin-4
      fluorescein and biotinylated-ovalbumin (OVA). CONCLUSIONS: Expression of a
      recombinant avidin with biotin-binding activity on the surface of E. coli was
      achieved using the autotransporter ShdA. This system is an alternative to bind
      biotinylated molecules to E. coli.

PMID- 29357101
TI  - A new genus and species of turtle blood fluke (Digenea: Schistosomatoidea) from
      the Mekong snail-eating turtle, Malayemys subtrijuga (Schlegel & Muller)
      (Testudines: Geoemydidae) in Vietnam, with a reassessment of related Asiatic
      turtle blood flukes and molecular phylogeny.
AB  - Platt sinuosus Roberts & Bullard n. g., n. sp. (type-species) infects the kidney
      and mesenteric blood vessels of Mekong snail-eating turtles, Malayemys subtrijuga
      (Schlegel & Muller), in the Mekong River Basin. Species of Platt Roberts &
      Bullard n. g. are unique by the combination of having a papillate ventral sucker,
      vasa efferentia that are dorsal to the gonads, a massive cirrus-sac that is
      directed anteriad or laterad, and a vitellarium that surrounds the intestinal
      caeca. The new species resembles Platt ocadiae (Takeuti, 1942) Roberts & Bullard
      n. comb. but differs from it by having an external seminal vesicle that overlaps
      with or is immediately posterior to the level of the ventral sucker. Seven
      species previously of Hapalorhynchus Stunkard, 1922 are reassigned herein to
      Platt: P. odhnerensis (Mehra, 1933) Roberts & Bullard n. comb.; P. yoshidai
      (Ozaki, 1939) Roberts & Bullard n. comb.; P. ocadiae; P. oschmarini (Belous,
      1963) Roberts & Bullard n. comb.; P. sutlejensis (Mehrotra, 1973) Roberts &
      Bullard n. comb.; P. synderi (Platt & Sharma, 2012) Roberts & Bullard n. comb.;
      and P. tkachi (Platt & Sharma, 2012) Roberts & Bullard n. comb. A dichotomous key
      to Platt spp. is provided. Hapalorhynchus sheilae (Mehrotra, 1973) Bourgat, 1990
      and Hapalorhynchus mica (Oshmarin, 1971) Bourgat, 1990 are considered as species
      inquirendae, and Hapalorhynchus indicus (Thapar, 1933) Price, 1934 and
      Hapalorhynchus macrotesticularis (Rohde, Lee, & Lim, 1968) Brooks & Sullivan,
      1981 are considered as species incertae sedis. Phylogenetic analysis of the large
      subunit rDNA (28S) showed P. sinuosus and P. snyderi to be sister taxa distinct
      from a monophyletic Hapalorhynchus and Coeuritrema platti Roberts & Bullard,
      2016.

PMID- 29357103
TI  - Outcomes of preterm birth and evidence synthesis.

PMID- 29357102
TI  - Methods of Estimating Kidney Function for Drug Dosing in Special Populations.
AB  - International guidelines recommend the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) method to monitor kidney function in chronic kidney
      disease using either creatinine- or cystatin C-based estimation methods. The
      choice of an estimation method to determine dosage for renally eliminated drugs
      is not as clear. For the majority of currently marketed drugs, the Cockcroft
      Gault equation with the Jaffe method, a non-isotope dilution mass spectrometry,
      standardized serum creatinine, was used to estimate kidney function to recommend
      dosing adjustment in kidney impairment. As the Cockcroft-Gault equation cannot be
      converted for isotope dilution mass spectrometry-traceable creatinine values and
      clinical laboratories now report estimated glomerular filtration (eGFR) rate by
      the Modified Diet in Renal Disease (MDRD) Equation or CKD-EPI, the eGFR is now
      more widely accepted for dosage adjustment recommendations. Cockcroft-Gault, MDRD
      Equation, and CKD-EPI creatinine-based methods were developed in specific
      populations, which included either none or a low proportion of obese individuals,
      pregnant women, older adults, and those with significant comorbid conditions.
      Clinical studies in these special populations have identified significant
      decreased accuracy, precision, and bias in the creatinine-based methods. Newer
      cystatin C-based estimation methods may significantly improve the ability to
      estimate kidney function to determine doses in the future. At this time, the
      increased cost and lack of standardization of serum cystatin C hinder routine
      use.

PMID- 29357104
TI  - Pretransplant defunctionalized bladder-overrated condition?
AB  - AIMS: The objective of this study was to evaluate the expression of bladder
      receptors in patients with defunctionalized bladder (DB) and to assess voiding
      behavior after refunctionalization. METHODS: A total of 68 pretransplant patients
      were divided in two groups: DB (diuresis <300 mL/24 h; n = 33) and NDB (non-DB;
      diuresis >=300 mL/24 h; n = 35). A sample of mucosa and detrusor at the site of
      the future ureteral implantation was collected. The following receptors were
      assessed by real-time polymerase chain reaction (qRT-PCR): M2 , M3 , alpha1D ,
      beta3 , P2X2 , P2X3 , TRPV1, TRPV4, TRPA1, and TRPM8. At 3, 6, and 12 months
      after transplant patients answered IPSS and ICIQ-OAB questionnaires and filled a
      3-day 24 h frequency/volume chart (FVC) at 6 and 12 months. RESULTS: The
      expression of all receptors in the mucosa and in the detrusor was similar in both
      groups, except from alpha1D , which was overexpressed in the detrusor of DB
      relatively to NDB group. ICIQ-OAB symptom score was similar between the groups at
      3, 6, and 12 months. There was a reduction of this score in both groups with
      time. The same pattern was found for IPSS score. Bother scores were similar
      between groups. No difference was observed for all FVC parameters between DB and
      NDB patients. CONCLUSION: Gene expression of bladder receptors involved in
      micturition control was similar in patients with or without DB. Bladder behavior
      had a similar pattern independently of pretransplant residual diuresis. These
      findings question the relevance of the term DB in pretransplant patients.

PMID- 29357106
TI  - Marked pseudoepitheliomatous hyperplasia secondary to a red-pigmented tattoo: a
      case report.

PMID- 29357105
TI  - Alcohol use and personality change in middle and older adulthood: Findings from
      the Health and Retirement Study.
AB  - OBJECTIVE: Personality is known to predict alcohol consumption, but how alcohol
      use is related to personality change is less clear, especially at older ages. The
      present study examined the effects of level of alcohol consumption and history of
      dependence on change in the Five-Factor Model personality traits in a national
      cohort of Americans aged over 50. METHOD: Over 10,000 adults who participated in
      2006-2008 waves of the Health and Retirement Study reported on personality and
      alcohol use and were followed over 4 years. RESULTS: Latent difference score
      models indicated decreases in Extraversion to be attenuated for individuals
      categorized as light-to-moderate drinkers at baseline, whereas decreases in
      Conscientiousness were accentuated by having experienced alcohol dependence
      symptoms. Moreover, personality difference scores correlated with changes in the
      amount of alcohol consumed at follow-up. CONCLUSIONS: The findings suggest that
      patterns of alcohol consumption are associated with changes in personality across
      the second half of the life span.

PMID- 29357107
TI  - Balancing exercise-induced weight loss with protein caloric requirement remains a
      challenge in overweight patients with cirrhosis.

PMID- 29357108
TI  - rs142362919 and rs7681187 Are cis-Regulatory Variations for Human UGT2B28 in
      Breast.

PMID- 29357109
TI  - A Guide to Robust Statistical Methods in Neuroscience.
AB  - There is a vast array of new and improved methods for comparing groups and
      studying associations that offer the potential for substantially increasing
      power, providing improved control over the probability of a Type I error, and
      yielding a deeper and more nuanced understanding of data. These new techniques
      effectively deal with four insights into when and why conventional methods can be
      unsatisfactory. But for the non-statistician, the vast array of new and improved
      techniques for comparing groups and studying associations can seem daunting,
      simply because there are so many new methods that are now available. This unit
      briefly reviews when and why conventional methods can have relatively low power
      and yield misleading results. The main goal is to suggest some general guidelines
      regarding when, how, and why certain modern techniques might be used. (c) 2018 by
      John Wiley & Sons, Inc.

PMID- 29357110
TI  - Hybridization Histochemistry of Neural Transcripts.
AB  - This unit presents protocols to locate RNA transcripts in tissues. Numerous
      approaches are detailed, including those that use radiolabeled or colorimetric
      probes. Also, the probes may be modified oligodeoxynucleotides, singly or in
      pairs, as well as ribonucleic acids. High sensitivity and specificity are
      obtained, especially with sets of oligodeoxynucleotide pairs. (c) 2018 by John
      Wiley & Sons, Inc.

PMID- 29357111
TI  - Imaging of Mitochondrial and Cytosolic Ca2+ Signals in Cultured Astrocytes.
AB  - This unit provides a step-by-step protocol for constructing cell type- and
      mitochondria-targeted GCaMP genetically encoded Ca2+ indicators (GECIs) for
      mitochondrial Ca2+ imaging in astrocytes. Mitochondrial Ca2+ plays a critical
      role in controlling cytosolic Ca2+ buffering, energy metabolism, and cellular
      signal transduction. Mitochondrial Ca2+ overload contributes to various
      pathological conditions, including neurodegeneration and apoptotic cell death in
      neurological diseases. Live-cell mitochondrial Ca2+ imaging is an important
      approach to understand mitochondrial Ca2+ dynamics and thus cell physiology and
      pathology. We implement astrocyte-specific mitochondrial targeting of GCaMP5G/6s
      (mito-GCaMP5G/6s). By loading X-Rhod-1 into astrocytes, we can simultaneously
      image mitochondrial and cytosolic Ca2+ signals. This protocol provides a novel
      approach to image mitochondrial Ca2+ dynamics as well as Ca2+ interplay between
      the endoplasmic reticulum and mitochondria. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29357112
TI  - Icon arrays help younger children's proportional reasoning.
AB  - We investigated the effects of two context variables, presentation format (icon
      arrays or numerical frequencies) and time limitation (limited or unlimited time),
      on the proportional reasoning abilities of children aged 7 and 10 years, as well
      as adults. Participants had to select, between two sets of tokens, the one that
      offered the highest likelihood of drawing a gold token, that is, the set of
      elements with the greater proportion of gold tokens. Results show that
      participants performed better in the unlimited time condition. Moreover, besides
      a general developmental improvement in accuracy, our results show that younger
      children performed better when proportions were presented as icon arrays, whereas
      older children and adults were similarly accurate in the two presentation format
      conditions. Statement of contribution What is already known on this subject?
      There is a developmental improvement in proportional reasoning accuracy. Icon
      arrays facilitate reasoning in adults with low numeracy. What does this study
      add? Participants were more accurate when they were given more time to make the
      proportional judgement. Younger children's proportional reasoning was more
      accurate when they were presented with icon arrays. Proportional reasoning
      abilities correlate with working memory, approximate number system, and
      subitizing skills.

PMID- 29357113
TI  - Toward a reliable, automated method of individual alpha frequency (IAF)
      quantification.
AB  - Individual alpha frequency (IAF) is a promising electrophysiological marker of
      interindividual differences in cognitive function. IAF has been linked with trait
      like differences in information processing and general intelligence, and provides
      an empirical basis for the definition of individualized frequency bands. Despite
      its widespread application, however, there is little consensus on the optimal
      method for estimating IAF, and many common approaches are prone to bias and
      inconsistency. Here, we describe an automated strategy for deriving two of the
      most prevalent IAF estimators in the literature: peak alpha frequency (PAF) and
      center of gravity (CoG). These indices are calculated from resting-state power
      spectra that have been smoothed using a Savitzky-Golay filter (SGF). We evaluate
      the performance characteristics of this analysis procedure in both empirical and
      simulated EEG data sets. Applying the SGF technique to resting-state data from n
      = 63 healthy adults furnished 61 PAF and 62 CoG estimates. The statistical
      properties of these estimates were consistent with previous reports. Simulation
      analyses revealed that the SGF routine was able to reliably extract target alpha
      components, even under relatively noisy spectral conditions. The routine
      consistently outperformed a simpler method of automated peak detection that did
      not involve spectral smoothing. The SGF technique is fast, open source, and
      available in two popular programming languages (MATLAB, Python), and thus can
      easily be integrated within the most popular M/EEG toolsets (EEGLAB, FieldTrip,
      MNE-Python). As such, it affords a convenient tool for improving the reliability
      and replicability of future IAF-related research.

PMID- 29357114
TI  - What is your diagnosis? Mediastinal mass in a dromedary camel.

PMID- 29357115
TI  - Differences in mortality in a cohort of cocaine use disorder patients with
      concurrent alcohol or opiates disorder.
AB  - AIMS: To study mortality in a cohort of cocaine use disorder patients, and
      compare results in those with concurrent alcohol or opiates disorder. DESIGN,
      SETTING AND PARTICIPANTS: A cohort of 10 539 cocaine use disorder individuals
      entering drug treatment in public out-patient centres in the city of Barcelona
      was followed from 1997 to 2011. Participants were divided at baseline into three
      groups: those with only cocaine use disorder (CUD), those with cocaine and
      alcohol use disorder but not opioid (CAUD) and those with cocaine and opioid use
      disorder (COUD). Mortality was assessed through the Spanish National Mortality
      Register. MEASUREMENTS: Crude mortality rates (CMR), standardized mortality
      ratios (SMR) and rate ratios (RR) were calculated for each group. A multivariable
      Cox regression model was fitted to obtain adjusted mortality hazard ratios (aHR)
      of CAUD and COUD with respect to CUD. Specific mortality causes were also
      examined. FINDINGS: The total of 716 deaths registered resulted in a CMR =
      6.0/1000 person-years (PY); 95% confidence interval (CI) = 5.1-7.0 for CUD, CMR =
      5.8/1000 PY (95% CI = 4.9-6.7) for CAUD and CMR = 20.7/1000 PY (95% CI = 18.8
      22.8) for COUD, with no significant differences among sexes. Compared with the
      general population, mortality was four times higher (SMR = 4.1, 95% CI = 3.5-4.8)
      among CUD, more than three times among CAUD (SMR = 3.4, 95% CI = 2.9-3.9) and
      more than 10 times among COUD (SMR = 11.6, 95% CI = 10.5-12.8), being always
      higher in women. External injuries, led by overdose, accumulated the biggest
      percentage of deaths among the three groups, but infectious diseases showed the
      highest excess mortality. Some differences regarding causes of death were
      observed between the three groups. CONCLUSIONS: Mortality risk and excess
      mortality are significantly greater among those with cocaine and opiates use
      disorder than among people with only cocaine use disorder or cocaine and alcohol
      use disorder.

PMID- 29357116
TI  - The PI3K/AKT signaling pathway in regulatory T-cell development, stability, and
      function.
AB  - The PI3K/AKT signaling pathway is an essential node in mammalian cells that
      controls cell growth, migration, proliferation, and metabolism. During the last
      decade, a number of works have demonstrated an important role for the PI3K/AKT
      pathway in regulatory T cell development, function, and stability. This review
      summarizes our current knowledge of how the PI3K/AKT pathway regulates thymic and
      peripheral Treg generation and function, with an emphasis on translation of these
      observations to therapies targeting Tregs in several pathologies.

PMID- 29357117
TI  - Crocin improved amyloid beta induced long-term potentiation and memory deficits
      in the hippocampal CA1 neurons in freely moving rats.
AB  - Extracellular beta-amyloid (Abeta) accumulation and deposition is the main
      factor, which causes synaptic loss and eventually cells death in Alzheimer's
      disease (AD). Memory loss and long-term potentiation (LTP) dysfunction in the
      hippocampus are involved in the AD. The involvement of crocin, as the main and
      active constituent of saffron extract in learning and memory processes, has been
      proposed. Here we investigated the probable therapeutic effect of crocin on
      memory, LTP, and neuronal apoptosis using in vivo Abeta models of the AD. The
      Abeta peptide (1-42) was bilaterally administered into the frontal-cortex using
      stereotaxic apparatus. Five hours after surgery, rats were given intraperitoneal
      crocin (30 mg/kg) daily, which repeated for 12 days. Barnes maze results showed
      that administration of crocin significantly improves spatial memory indicators
      such as latency time to achieving the target hole and the number of errors when
      compared to Abeta-group. Passive avoidance test revealed that crocin
      significantly increased the step-through-latency compared to Abeta-treated alone.
      These learning deficits in Abeta-treated animals correlated with a reduction of
      LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved
      population spike amplitude and mean field excitatory postsynaptic potentials
      (fEPSP) slope reduction induced by Abeta. Neuronal apoptosis was detected by
      TUNEL assay and the expression levels of c-Fos proteins were examined by Western
      blotting. Crocin significantly reduced the number of TUNEL-positive cells in the
      CA1 region and decreased c-Fos in the hippocampus compared to Abeta-group. In
      vivo Abeta treatment altered significantly the electrophysiological properties of
      CA1 neurons and crocin further confirmed a neuroprotective action against Abeta
      toxicity.

PMID- 29357118
TI  - Comparison of long-term clinical outcomes among different vascularized lymph node
      transfers: 6-year experience of a single center's approach to the treatment of
      lymphedema.

PMID- 29357119
TI  - 3D, Reconfigurable, Multimodal Electronic Whiskers via Directed Air Assembly.
AB  - A batch-assembly technique for forming 3D electronics on shape memory polymer
      substrates is demonstrated and is used to create dense, highly sensitive,
      multimodal arrays of electronic whiskers. Directed air flow at temperatures above
      the substrate's glass transition temperature transforms planar
      photolithographically defined resistive sensors from 2D precursors into shape
      tunable, deterministic 3D assemblies. Reversible 3D assembly and flattening is
      achieved by exploiting the shape memory properties of the substrate, enabling
      context-driven shape reconfiguration to isolate/enhance specific sensing modes.
      In particular, measurement schemes and device configurations are introduced that
      allow for the sensing of temperature, stiffness, contact force, proximity, and
      surface texture and roughness. The assemblies offer highly spatiotemporally
      resolved, wide-range measurements of surface topology (50 nm to 500 um), material
      stiffness (200 kPa to 7.5 GPa), and temperature (0-100  degrees C), with response
      times of <250 us. The development of a scalable process for 3D assembly of
      reconfigurable electronic sensors, as well as the large breadth and sensitivity
      of complex sensing modes demonstrated, has applications in the growing fields of
      3D assembly, electronic skin, and human-machine interfaces.

PMID- 29357120
TI  - Magnetic resonance perfusion for differentiating low-grade from high-grade
      gliomas at first presentation.
AB  - BACKGROUND: Gliomas are the most common primary brain tumour. They are graded
      using the WHO classification system, with Grade II-IV astrocytomas,
      oligodendrogliomas and oligoastrocytomas. Low-grade gliomas (LGGs) are WHO Grade
      II infiltrative brain tumours that typically appear solid and non-enhancing on
      magnetic resonance imaging (MRI) scans. People with LGG often have little or no
      neurologic deficit, so may opt for a watch-and-wait-approach over surgical
      resection, radiotherapy or both, as surgery can result in early neurologic
      disability. Occasionally, high-grade gliomas (HGGs, WHO Grade III and IV) may
      have the same MRI appearance as LGGs. Taking a watch-and-wait approach could be
      detrimental for the patient if the tumour progresses quickly. Advanced imaging
      techniques are increasingly used in clinical practice to predict the grade of the
      tumour and to aid clinical decision of when to intervene surgically. One such
      advanced imaging technique is magnetic resonance (MR) perfusion, which detects
      abnormal haemodynamic changes related to increased angiogenesis and vascular
      permeability, or "leakiness" that occur with aggressive tumour histology. These
      are reflected by changes in cerebral blood volume (CBV) expressed as rCBV (ratio
      of tumoural CBV to normal appearing white matter CBV) and permeability, measured
      by Ktrans. OBJECTIVES: To determine the diagnostic test accuracy of MR perfusion
      for identifying patients with primary solid and non-enhancing LGGs (WHO Grade II)
      at first presentation in children and adults. In performing the quantitative
      analysis for this review, patients with LGGs were considered disease positive
      while patients with HGGs were considered disease negative.To determine what
      clinical features and methodological features affect the accuracy of MR
      perfusion. SEARCH METHODS: Our search strategy used two concepts: (1) glioma and
      the various histologies of interest, and (2) MR perfusion. We used structured
      search strategies appropriate for each database searched, which included: MEDLINE
      (Ovid SP), Embase (Ovid SP), and Web of Science Core Collection (Science Citation
      Index Expanded and Conference Proceedings Citation Index). The most recent search
      for this review was run on 9 November 2016.We also identified 'grey literature'
      from online records of conference proceedings from the American College of
      Radiology, European Society of Radiology, American Society of Neuroradiology and
      European Society of Neuroradiology in the last 20 years. SELECTION CRITERIA: The
      titles and abstracts from the search results were screened to obtain full-text
      articles for inclusion or exclusion. We contacted authors to clarify or obtain
      missing/unpublished data.We included cross-sectional studies that performed
      dynamic susceptibility (DSC) or dynamic contrast-enhanced (DCE) MR perfusion or
      both of untreated LGGs and HGGs, and where rCBV and/or Ktrans values were
      reported. We selected participants with solid and non-enhancing gliomas who
      underwent MR perfusion within two months prior to histological confirmation. We
      excluded studies on participants who received radiation or chemotherapy before MR
      perfusion, or those without histologic confirmation. DATA COLLECTION AND
      ANALYSIS: Two review authors extracted information on study characteristics and
      data, and assessed the methodological quality using the Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS-2) tool. We present a summary of the study
      characteristics and QUADAS-2 results, and rate studies as good quality when they
      have low risk of bias in the domains of reference standard of tissue diagnosis
      and flow and timing between MR perfusion and tissue diagnosis.In the quantitative
      analysis, LGGs were considered disease positive, while HGGs were disease
      negative. The sensitivity refers to the proportion of LGGs detected by MR
      perfusion, and specificity as the proportion of detected HGGs. We constructed two
      by-two tables with true positives and false negatives as the number of correctly
      and incorrectly diagnosed LGG, respectively, while true negatives and false
      positives are the number of correctly and incorrectly diagnosed HGG,
      respectively.Meta-analysis was performed on studies with two-by-two tables, with
      further sensitivity analysis using good quality studies. Limited data precluded
      regression analysis to explore heterogeneity but subgroup analysis was performed
      on tumour histology groups. MAIN RESULTS: Seven studies with small sample sizes
      (4 to 48) met our inclusion criteria. These were mostly conducted in university
      hospitals and mostly recruited adult patients. All studies performed DSC MR
      perfusion and described heterogeneous acquisition and post-processing methods.
      Only one study performed DCE MR perfusion, precluding quantitative analysis.Using
      patient-level data allowed selection of individual participants relevant to the
      review, with generally low risks of bias for the participant selection, reference
      standard and flow and timing domains. Most studies did not use a pre-specified
      threshold, which was considered a significant source of bias, however this did
      not affect quantitative analysis as we adopted a common rCBV threshold of 1.75
      for the review. Concerns regarding applicability were low.From published and
      unpublished data, 115 participants were selected and included in the meta
      analysis. Average rCBV (range) of 83 LGGs and 32 HGGs were 1.29 (0.01 to 5.10)
      and 1.89 (0.30 to 6.51), respectively. Using the widely accepted rCBV threshold
      of <1.75 to differentiate LGG from HGG, the summary sensitivity/specificity
      estimates were 0.83 (95% CI 0.66 to 0.93)/0.48 (95% CI 0.09 to 0.90). Sensitivity
      analysis using five good quality studies yielded sensitivity/specificity of 0.80
      (95% CI 0.61 to 0.91)/0.67 (95% CI 0.07 to 0.98). Subgroup analysis for tumour
      histology showed sensitivity/specificity of 0.92 (95% CI 0.55 to 0.99)/0.42 (95%
      CI 0.02 to 0.95) in astrocytomas (6 studies, 55 participants) and 0.77 (95% CI
      0.46 to 0.93)/0.53 (95% CI 0.14 to 0.88) in oligodendrogliomas+oligoastrocytomas
      (6 studies, 56 participants). Data were too sparse to investigate any differences
      across subgroups. AUTHORS' CONCLUSIONS: The limited available evidence precludes
      reliable estimation of the performance of DSC MR perfusion-derived rCBV for the
      identification of grade in untreated solid and non-enhancing LGG from that of
      HGG. Pooled data yielded a wide range of estimates for both sensitivity (range
      66% to 93% for detection of LGGs) and specificity (range 9% to 90% for detection
      of HGGs). Other clinical and methodological features affecting accuracy of the
      technique could not be determined from the limited data. A larger sample size of
      both LGG and HGG, preferably using a standardised scanning approach and with an
      updated reference standard incorporating molecular profiles, is required for a
      definite conclusion.

PMID- 29357121
TI  - Scalable 2D Hierarchical Porous Carbon Nanosheets for Flexible Supercapacitors
      with Ultrahigh Energy Density.
AB  - 2D carbon nanomaterials such as graphene and its derivatives, have gained
      tremendous research interests in energy storage because of their high capacitance
      and chemical stability. However, scalable synthesis of ultrathin carbon
      nanosheets with well-defined pore architectures remains a great challenge.
      Herein, the first synthesis of 2D hierarchical porous carbon nanosheets (2D-HPCs)
      with rich nitrogen dopants is reported, which is prepared with high scalability
      through a rapid polymerization of a nitrogen-containing thermoset and a
      subsequent one-step pyrolysis and activation into 2D porous nanosheets. 2D-HPCs,
      which are typically 1.5 nm thick and 1-3 um wide, show a high surface area (2406
      m2 g-1 ) and with hierarchical micro-, meso-, and macropores. This 2D and
      hierarchical porous structure leads to robust flexibility and good energy-storage
      capability, being 139 Wh kg-1 for a symmetric supercapacitor. Flexible
      supercapacitor devices fabricated by these 2D-HPCs also present an ultrahigh
      volumetric energy density of 8.4 mWh cm-3 at a power density of 24.9 mW cm-3 ,
      which is retained at 80% even when the power density is increased by 20-fold. The
      devices show very high electrochemical life (96% retention after 10000
      charge/discharge cycles) and excellent mechanical flexibility.

PMID- 29357122
TI  - Adaptation to stimulus orientation in mouse primary visual cortex.
AB  - Information processing in the visual system is shaped by recent stimulus history,
      such that prolonged viewing of an adapting stimulus can alter the perception of
      subsequently presented test stimuli. In the tilt-after-effect, the perceived
      orientation of a grating is often repelled away from the orientation of a
      previously viewed adapting grating. A possible neural correlate for the tilt
      after-effect has been described in cat and macaque primary visual cortex (V1),
      where adaptation produces repulsive shifts in the orientation tuning curves of V1
      neurons. We investigated adaptation to stimulus orientation in mouse V1 to
      determine whether known species differences in orientation processing, notably V1
      functional architecture and proportion of tightly tuned cells, are important for
      these repulsive shifts. Unlike the consistent repulsion reported in other
      species, we found that repulsion was only about twice as common as attraction in
      our mouse data. Furthermore, adapted responses were attenuated across all
      orientations. A simple model that captured key physiological findings reported in
      cats and mice indicated that the greater proportion of broadly tuned neurons in
      mice may explain the observed species differences in adaptation.

PMID- 29357123
TI  - Triglyceride Metabolism in the Liver.
AB  - Triglyceride molecules represent the major form of storage and transport of fatty
      acids within cells and in the plasma. The liver is the central organ for fatty
      acid metabolism. Fatty acids accrue in liver by hepatocellular uptake from the
      plasma and by de novo biosynthesis. Fatty acids are eliminated by oxidation
      within the cell or by secretion into the plasma within triglyceride-rich very low
      density lipoproteins. Notwithstanding high fluxes through these pathways, under
      normal circumstances the liver stores only small amounts of fatty acids as
      triglycerides. In the setting of overnutrition and obesity, hepatic fatty acid
      metabolism is altered, commonly leading to the accumulation of triglycerides
      within hepatocytes, and to a clinical condition known as nonalcoholic fatty liver
      disease (NAFLD). In this review, we describe the current understanding of fatty
      acid and triglyceride metabolism in the liver and its regulation in health and
      disease, identifying potential directions for future research. Advances in
      understanding the molecular mechanisms underlying the hepatic fat accumulation
      are critical to the development of targeted therapies for NAFLD. (c) 2018
      American Physiological Society. Compr Physiol 8:1-22, 2018.

PMID- 29357124
TI  - Role of Perivascular Adipose Tissue in Health and Disease.
AB  - Perivascular adipose tissue (PVAT) is cushion of fat tissue surrounding blood
      vessels, which is phenotypically different from other adipose tissue depots. PVAT
      is composed of adipocytes and stromal vascular fraction, constituted by different
      populations of immune cells, endothelial cells, and adipose-derived stromal
      cells. It expresses and releases an important number of vasoactive factors with
      paracrine effects on vascular structure and function. In healthy individuals,
      these factors elicit a net anticontractile and anti-inflammatory paracrine effect
      aimed at meeting hemodynamic and metabolic demands of specific organs and regions
      of the body. Pathophysiological situations, such as obesity, diabetes or
      hypertension, induce changes in its amount and in the expression pattern of
      vasoactive factors leading to a PVAT dysfunction in which the beneficial
      paracrine influence of PVAT is shifted to a pro-oxidant, proinflammatory,
      contractile, and trophic environment leading to functional and structural
      cardiovascular alterations and cardiovascular disease. Many different PVATs
      surrounding a variety of blood vessels have been described and exhibit regional
      differences. Both protective and deleterious influence of PVAT differs regionally
      depending on the specific vascular bed contributing to variations in the
      susceptibility of arteries and veins to vascular disease. PVAT therefore, might
      represent a novel target for pharmacological intervention in cardiovascular
      disease. (c) 2018 American Physiological Society. Compr Physiol 8:23-59, 2018.

PMID- 29357125
TI  - Hemorrhagic Shock and the Microvasculature.
AB  - The microvasculature plays a central role in the pathophysiology of hemorrhagic
      shock and is also involved in arguably all therapeutic attempts to reverse or
      minimize the adverse consequences of shock. Microvascular studies specific to
      hemorrhagic shock were reviewed and broadly grouped depending on whether data
      were obtained on animal or human subjects. Dedicated sections were assigned to
      microcirculatory changes in specific organs, and major categories of
      pathophysiological alterations and mechanisms such as oxygen distribution,
      ischemia, inflammation, glycocalyx changes, vasomotion, endothelial dysfunction,
      and coagulopathy as well as biomarkers and some therapeutic strategies.
      Innovative experimental methods were also reviewed for quantitative
      microcirculatory assessment as it pertains to changes during hemorrhagic shock.
      The text and figures include representative quantitative microvascular data
      obtained in various organs and tissues such as skin, muscle, lung, liver, brain,
      heart, kidney, pancreas, intestines, and mesentery from various species including
      mice, rats, hamsters, sheep, swine, bats, and humans. Based on reviewed findings,
      a new integrative conceptual model is presented that includes about 100 systemic
      and local factors linked to microvessels in hemorrhagic shock. The combination of
      systemic measures with the understanding of these processes at the microvascular
      level is fundamental to further develop targeted and personalized interventions
      that will reduce tissue injury, organ dysfunction, and ultimately mortality due
      to hemorrhagic shock. Published 2018. Compr Physiol 8:61-101, 2018.

PMID- 29357126
TI  - Integration of Central and Peripheral Regulation of the Circulation during
      Exercise: Acute and Chronic Adaptations.
AB  - Physical movement lasting any more than a few seconds (e.g., exercise), requires
      coordination of motor control with concomitant changes in the cardiovascular and
      respiratory support necessary to respond to the rapid increases in metabolic
      demand. Without such coordination, delivery of oxygen and removal of waste
      products become rate limiting and will restrict the duration, speed, and quality
      of movement. Fortunately, under healthy conditions, the central and peripheral
      nervous systems contribute importantly to this remarkable level of coordination
      via complex mechanisms that remain to be fully elucidated. The purposes of this
      review are to present the current state of knowledge regarding: (i) mechanisms by
      which the body maintains appropriate perfusion pressure to all organs during
      acute bouts of exercise, and (ii) alterations occurring in these mechanisms via
      central nervous system adaptations when exercise is performed or not performed on
      a regular basis (e.g., physically active versus sedentary lifestyle,
      respectively). Results from studies performed in humans and laboratory animals
      provide the reader a well-rounded knowledge base. They are intended to instill an
      appreciation of what is known, and not known, about how the brain regulates the
      cardiovascular system during acute bouts of exercise, and the adaptations that
      occur when individuals exercise regularly versus when chronically sedentary.
      Discussion of the latter is intended to provide novel mechanisms for the
      increased incidence of cardiovascular disease in sedentary individuals versus a
      reduced incidence in individuals who are regularly active. (c) 2018 American
      Physiological Society. Compr Physiol 8:103-151, 2018.

PMID- 29357127
TI  - Molecular Regulation of Sprouting Angiogenesis.
AB  - The term angiogenesis arose in the 18th century. Several studies over the next
      100 years laid the groundwork for initial studies performed by the Folkman
      laboratory, which were at first met with some opposition. Once overcome, the
      angiogenesis field has flourished due to studies on tumor angiogenesis and
      various developmental models that can be genetically manipulated, including mice
      and zebrafish. In addition, new discoveries have been aided by the ability to
      isolate primary endothelial cells, which has allowed dissection of various steps
      within angiogenesis. This review will summarize the molecular events that control
      angiogenesis downstream of biochemical factors such as growth factors, cytokines,
      chemokines, hypoxia-inducible factors (HIFs), and lipids. These and other stimuli
      have been linked to regulation of junctional molecules and cell surface
      receptors. In addition, the contribution of cytoskeletal elements and regulatory
      proteins has revealed an intricate role for mobilization of actin, microtubules,
      and intermediate filaments in response to cues that activate the endothelium.
      Activating stimuli also affect various focal adhesion proteins, scaffold
      proteins, intracellular kinases, and second messengers. Finally,
      metalloproteinases, which facilitate matrix degradation and the formation of new
      blood vessels, are discussed, along with our knowledge of crosstalk between the
      various subclasses of these molecules throughout the text. Compr Physiol 8:153
      235, 2018.

PMID- 29357129
TI  - Adrenocortical Stress Response during the Course of Critical Illness.
AB  - Critically ill patients have elevated plasma cortisol concentrations, in
      proportion to illness severity. This was traditionally attributed exclusively to
      a central activation of the hypothalamus-pituitary axis. However, low rather than
      high plasma ACTH concentrations have been reported in critically ill patients,
      with loss of diurnal ACTH and cortisol rhythm. Low ACTH together with high
      cortisol is referred to as "ACTH-cortisol dissociation." Although cortisol
      production is somewhat increased with inflammation, a reduced cortisol breakdown
      explains to a larger extent the hypercortisolism during critical illness.
      Inflammation-driven decrease in cortisol binding proteins further increase the
      active free cortisol fraction. Several drugs administered to ICU patients
      suppress plasma cortisol in a dose-dependent manner. Sustained low circulating
      ACTH might contribute to adrenal atrophy and dysfunction in the prolonged phase
      of critical illness. In the acute phase of sepsis or septic shock, a condition
      referred to as "relative adrenal insufficiency" has been suggested to ensue from
      glucocorticoid resistance and insufficiently elevated circulating cortisol to
      overcome such resistance, with pathological changes possibly occurring at every
      level of the HPA axis. However, it remains highly controversial whether tissue
      specific glucocorticoid resistance is adaptive or maladaptive, how to diagnose
      "relative" adrenal insufficiency, and how it should be treated. Large RCTs,
      investigating the effect of 200 mg/d hydrocortisone treatment for sepsis or
      septic shock have shown conflicting, mainly negative, results. Not taking into
      account the reduced cortisol breakdown, which increases the risk of overdosing
      hydrocortisone, might have played a role. Further research on diagnostic,
      therapeutic and dosing aspects is urgently warranted. Compr Physiol 8:283-298,
      2018.

PMID- 29357131
TI  - Structure and Function of Bone Marrow Adipocytes.
AB  - Adipocytes are heterogeneous cells strongly linked to energy storage and
      disposal. In parallel, adipocytes are endowed with an extensive portfolio of
      endocrine molecules, whose secretion varies depending on nutritional status.
      Marrow adipose tissue (MAT) has specific characteristics that are not shared by
      white (WAT) or brown (BAT) adipose tissue. First, marrow adipocytes and
      osteoblasts are terminally differentiated cells that originate from the same bone
      marrow mesenchymal stromal cell. Differently from WAT adipocytes, marrow
      adipocytes expand under conditions of energy restriction and seem to be not
      influenced by energy surplus, at least in humans. Over the last few years,
      several lines of evidence have suggested that bone cells and MAT are mutually
      connected regarding the modulation of both energy metabolism and bone remodeling.
      Adipokines (e.g., adiponectin, leptin, and chemerin), incretins (GLP1 and GIP),
      and several classical hormones (e.g., GH and insulin) are biochemical components
      involved in the modulation of bone remodeling, marrow adipogenesis, and energy
      metabolism. As expected, metabolic and nutritional diseases such as diabetes
      mellitus and anorexia nervosa (AN) greatly affect MAT quantity and quality as
      well as bone strength. Although the interest in MAT started recently, the rapid
      advances in current technology have expedited unprecedented growth of knowledge
      in this area. The present review intends to give to the reader an up-to-date
      perspective about MAT structure and physiology as well as its involvement in
      metabolic and nutritional diseases such as diabetes mellitus and ano-rexia. (c)
      2018 American Physiological Society. Compr Physiol 8:315-349, 2018.

PMID- 29357132
TI  - Leptin Function and Regulation.
AB  - We summarize the biological impact of leptin signaling as well as the molecular
      and cellular characteristics of leptin action. Our focus is principally in the
      central nervous system and we describe the properties of the neuronal networks
      that are mediators of leptin's effects on ingestive behavior, energy balance, and
      the reproductive system. The molecular targets of leptin's effects are also
      responsible for the attenuation and termination of the intracellular signal
      transduction pathway for leptin, providing a clear understanding of the
      mechanisms leading to leptin resistance or insensitivity. Using the tools of
      comparative biology, we explore the potential functions of leptin in fish and
      birds. Based on the highly variable expression of leptin in multiple tissues, a
      clear lack of expression of leptin in adipocytes in numerous species of fish and
      birds and an absence of changes of leptin concentrations in blood that are
      correlated with changes in nutritional status, it is clear that leptin is
      unlikely to function as a signal for triglyceride stores in nonmammalian species.
      This comparative survey serves to highlight the unique function of leptin in
      mammalian biology as a modulator of energy balance, sexual development, and
      fertility. (c) 2018 American Physiological Society. Compr Physiol 8:351-369,
      2018.

PMID- 29357133
TI  - Pathophysiologic Mechanisms and Current Treatments for Cutaneous Sequelae of Burn
      Wounds.
AB  - Burn injuries are a pervasive clinical problem. Extensive thermal trauma can be
      life-threatening or result in long-lasting complications, generating a
      significant impact on quality of life for patients as well as a cost burden to
      the healthcare system. The importance of addressing global or systemic issues
      such as resuscitation and management of inhalation injuries is not disputed but
      is beyond the scope of this review, which focuses on cutaneous pathophysiologic
      mechanisms for current treatments, both in the acute and long-term settings.
      Pathophysiological mechanisms of burn progression and wound healing are mediated
      by highly complex cascades of cellular and biochemical events, which become
      dysregulated in slow-healing wounds such as burns. Burns can result in
      fibroproliferative scarring, skin contractures, or chronic wounds that take weeks
      or months to heal. Burn injuries are highly individualized owing to wound
      specific differences such as burn depth and surface area, in addition to patient
      specific factors including genetics, immune competency, and age. Other extrinsic
      complications such as microbial infection can complicate wound healing, resulting
      in prolonged inflammation and delayed re-epithelialization. Although mortality is
      decreasing with advancements in burn care, morbidity from postburn deformities
      continues to be a challenge. Optimizing specialized acute care and late burn
      outcome intervention on a patient-by-patient basis is critical for successful
      management of burn wounds and the associated pathological scar outcome.
      Understanding the fundamentals of integument physiology and the cellular
      processes involved in wound healing is essential for designing effective
      treatment strategies for burn wound care as well as development of future
      therapies. Published 2018. Compr Physiol 8:371-405, 2018.

PMID- 29357130
TI  - Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis.
AB  - Short-chain fatty acids (SCFA; acetate, propionate, and butyrate) are generated
      in colon by bacterial fermentation of dietary fiber. Though diffusion in
      protonated form is a significant route, carrier-mediated mechanisms constitute
      the major route for the entry of SCFA in their anionic form into colonic
      epithelium. Several transport systems operate in cellular uptake of SCFA. MCT1
      (SLC16A1) and MCT4 (SLC16A3) are H+-coupled and mediate electroneutral transport
      of SCFA (H+: SCFA stoichiometry; 1:1). MCT1 is expressed both in the apical
      membrane and basolateral membrane of colonic epithelium whereas MCT4 specifically
      in the basolateral membrane. SMCT1 (SLC5A8) and SMCT2 (SLC5A12) are Na+-coupled;
      SMCT1-mediated transport is electrogenic (Na+: SCFA stoichiometry; 2:1) whereas
      SMCT2-mediated transport is electroneutral (Na+: SCFA stoichiometry; 1:1). SMCT1
      and SMCT2 are expressed exclusively in the apical membrane. An anion-exchange
      mechanism also operates in the apical membrane in which SCFA entry in anionic
      form is coupled to bicarbonate efflux; the molecular identity of this exchanger
      however remains unknown. All these transporters are subject to regulation,
      notably by their substrates themselves; this process involves cell-surface
      receptors with SCFA as signaling molecules. There are significant alterations in
      the expression of these transporters in ulcerative colitis and colon cancer. The
      tumor-associated changes occur via transcriptional regulation by p53 and
      HIF1alpha and by promoter methylation. As SCFA are obligatory for optimal colonic
      health, the transporters responsible for the entry and transcellular transfer of
      these bacterial products in colonic epithelium are critical determinants of
      colonic function under physiological conditions and in disease states. (c) 2018
      American Physiological Society. Compr Physiol 8:299-314, 2018.

PMID- 29357128
TI  - Contribution of Adipose Tissue to Development of Cancer.
AB  - Solid tumor growth and metastasis require the interaction of tumor cells with the
      surrounding tissue, leading to a view of tumors as tissue-level phenomena rather
      than exclusively cell-intrinsic anomalies. Due to the ubiquitous nature of
      adipose tissue, many types of solid tumors grow in proximate or direct contact
      with adipocytes and adipose-associated stromal and vascular components, such as
      fibroblasts and other connective tissue cells, stem and progenitor cells,
      endothelial cells, innate and adaptive immune cells, and extracellular signaling
      and matrix components. Excess adiposity in obesity both increases risk of cancer
      development and negatively influences prognosis in several cancer types, in part
      due to interaction with adipose tissue cell populations. Herein, we review the
      cellular and noncellular constituents of the adipose "organ," and discuss the
      mechanisms by which these varied microenvironmental components contribute to
      tumor development, with special emphasis on obesity. Due to the prevalence of
      breast and prostate cancers in the United States, their close anatomical
      proximity to adipose tissue depots, and their complex epidemiologic associations
      with obesity, we particularly highlight research addressing the contribution of
      adipose tissue to the initiation and progression of these cancer types. Obesity
      dramatically modifies the adipose tissue microenvironment in numerous ways,
      including induction of fibrosis and angiogenesis, increased stem cell abundance,
      and expansion of proinflammatory immune cells. As many of these changes also
      resemble shifts observed within the tumor microenvironment, proximity to adipose
      tissue may present a hospitable environment to developing tumors, providing a
      critical link between adiposity and tumorigenesis. (c) 2018 American
      Physiological Society. Compr Physiol 8:237-282, 2018.

PMID- 29357136
TI  - The Effects of Herbivorous Snails on Submerged Macrophyte Communities in
      Minnesota Lakes.
AB  - The influence of herbivorous snails on freshwater macrophytes was examined both
      in the laboratory and the field. In the laboratory, 14 macrophyte species grown
      in the absence of herbivores had growth rates ranging from 1-10%/d. When grown
      with four densities of herbivorous snails, species that grew fastest in the
      absence of herbivores were, in general, most negatively influenced by grazing. In
      food choice tests, snails typically preferred the plant species that grew fastest
      in the absence of herbivores. Snail densities were manipulated in a small
      mesotrophic lake, Christmas Lake. In areas where high snail densities were
      maintained, macrophyte species richness decreased, and the plants remaining were
      the species least preferred in laboratory choice tests. In surveys of eight
      additional lakes having a range of snail densities, the relationship between
      snail density and macrophyte species composition and diversity was consistent
      with the laboratory and Christmas Lake results. The levels of herbivore damage in
      the lake were measured for one macrophyte species. For the leaves examined, from
      6 to 13% of the total leaf area was lost to herbivores. These results demonstrate
      that herbivorous snails can strongly influence the distribution, abundance, and
      diversity of freshwater macrophytes, and suggest that the role of herbivores in
      freshwater macrophyte communities may be similar to their role in terrestrial and
      marine communities.

PMID- 29357137
TI  - Beech Range Extension and Vegetation History: Pollen Stratigraphy of Two
      Wisconsin Lakes.
AB  - The pollen stratigraphy of two small lakes in eastern Wisconsin (Radtke Lake,
      Washington county, and Gass Lake, Manitowoc County) records the Holocene (past 10
      000 yr) spread of beech (Fagus grandifolia: Fagaceae). Radiocarbon dates were
      obtained for the oldest stratigraphic levels at which beech pollen appeared
      consistently in amounts > 0.5% of terrestrial pollen. A spatially continuous
      pattern of beech expansion from the north was ruled out, because beech trees grew
      in Wisconsin by 6000 BP, 2000 yr before adjacent populations were established to
      the north. Alternative geographic patterns of speed (from the south or east) were
      spatially discontinuous, requiring seed dispersal distances of perhaps 25-130 km.
      That beechnuts could be dispersed across such distances suggests (1) the
      involvement of Blue Jays, Passenger Pigeons, or other vertebrates, and (2) a
      capacity for reaching climatically controlled range limits, given sufficient time
      despite such discontinuities in habitat. A lag 1000-2000 yr between the
      establishment of source populations in Michigan and Indiana and the appearance of
      beech in Wisconsin suggests that low-probability dispersal events were involved
      and that dispersal constraints limited the range of beech during this time,
      although climatic and edaphic explanations for the lag cannot be ruled out.
      Pollen data from the two sites reveal other features of vegetation history in
      eastern Wisconsin: an open Picea-Fraxinus woodland prior to 11 000 BP; sequence
      of Picea, Abies, Betula, and then Pinus forests between 11 000 and 7500 BP; the
      establishment of a coniferous/deciduous forest ecotone ("tension zone")  degrees 
      7000 BP in this region; and the presence of Quercus-dominanted deciduous forests
      from 7000 BP until 110 BP (time of Euro-American settlement), a period punctuated
      by a gradual decrease in Ulmus populations ( degrees  4500 and 5700 BP at the two
      sites) and by an increase in mesophytic tree abundance at the expense of Quercus
      after 3500 BP.

PMID- 29357135
TI  - Dynamical localization of a thylakoid membrane binding protein is required for
      acquisition of photosynthetic competency.
AB  - Vipp1 is highly conserved and essential for photosynthesis, but its function is
      unclear as it does not participate directly in light-dependent reactions. We
      analyzed Vipp1 localization in live cyanobacterial cells and show that Vipp1 is
      highly dynamic, continuously exchanging between a diffuse fraction that is
      uniformly distributed throughout the cell and a punctate fraction that is
      concentrated at high curvature regions of the thylakoid located at the cell
      periphery. Experimentally perturbing the spatial distribution of Vipp1 by
      relocalizing it to the nucleoid causes a severe growth defect during the
      transition from non-photosynthetic (dark) to photosynthetic (light) growth.
      However, the same perturbation of Vipp1 in dark alone or light alone growth
      conditions causes no growth or thylakoid morphology defects. We propose that the
      punctuated dynamics of Vipp1 at the cell periphery in regions of high thylakoid
      curvature enable acquisition of photosynthetic competency, perhaps by
      facilitating biogenesis of photosynthetic complexes involved in light-dependent
      reactions of photosynthesis.

PMID- 29357138
TI  - Facilitative and Inhibitory Interactions Among Estuarine Meiobenthic Harpacticoid
      Copepods.
AB  - In the meiofauna communities of Louisiana estuaries (USA), the harpacticoid
      copepods Scottolana canadensis and Pseudostenhelia wellsi are predominant
      species. Scottolana canadensis is a semisessile burrow-dweller capable of
      subsurface suspension and deposit feeding. Pseudostenhelia wellsi is also
      semisessile but builds extensive networks of mucus tubes within the top 1 cm of
      muddy sediments, and appears to graze on its inner tubewalls. Tube building by P.
      wellsi generates meiofauna-sized structure and adds cohesiveness to surface
      sediments, as well as providing potential food and grazing substrates for other
      meiofuna. Monospecific patches of P. wellsi and S. canadensis (250 individuals/5
      cm2 ) were artificially generated in laboratory microcosms to determine if the
      unique lifestyle and sedimentary effects of either species facilitate or inhibit
      colonization by two other errant, burrowing harpacticoids common in the
      community, Nitrocra lacustris and Cletocamptus deitersi. These two species share
      similar foraging and burrowing behaviors and similar effects on sediment
      structure, which sharply contrast with those of P. wellsi and S. canadensis.
      Pseudostenhelia wellsi tube patches facilitated colonization by both S.
      canadensis and N. lacustris, but strongly inhibited colonization by C. deitersi.
      Scottolana canadensis patches were unattractive to N. lacustris. As P. wellsi
      showed the strongest effects on colonization by other harpacticoids, its
      mechanisms of facilitation/inhibition were also studied. In laboratory
      microcosms, cultured S. canadensis and N. lacustris were offered patches of azoic
      sediments, mucin-enriched sediments without structure, azoic sediments with agar
      tube mimics (structure), and sediments with natural P. wellsi tubes (mucus and
      structure). Both mucus enrichment and inert tube structure acted as strong
      facilitants to N. lacustris copepodites and adults overall. However, neither
      effect alone facilitated patch colonization by N. lacustris adult females and S.
      canadensis copepodites and adults. Their colonization was facilitated
      specifically by natural P. wellsi tubes. These experiments demonstrate that
      species interactions in harpacticoid communities can quickly influence spatial
      patterns, and those patterns may be mediated by species-specific effects on the
      sedimentary environment (e.g., mucus tube, burrows, increased flushing,
      erodability, etc.). However, spatial patterns cannot be predicted easily by
      contrasting the compatibility of one species' biogenic effects with those of
      another.

PMID- 29357139
TI  - Chihuahuan Desert Annuals: Importance of Water and Nitrogen.
AB  - We examined the effects of water supplementation and nitrogen amendment on
      biomass, cover, and density of annual plants on a termite-free and a termite
      present area in the Chihuahuan Desert. Soil moisture was higher in the termite
      than in the termite-free plots, and in the watered than in the unwatered plots
      during the spring and summer. There were no differences in soil moisture among
      plots during the winter. Soil nitrogen was higher in the termite-free than in the
      termite plots. There were no differences in total plant biomass produced in
      termite and termite-free areas. There were significant differences in relative
      abundances of species among treatments. natural rainfall was sufficient for
      maximum spring-annual biomass development on all plots except for the termite
      free unfertilized, unwatered plots. These were the driest plots but had high soil
      nitrogen. Most of the herbaceous species responded to the water amendments by
      lengthening growing seasons, increasing density, or increasing biomass. When
      there was sufficient water for most of the spring annuals, high soil nitrogen
      levels favored increased densities and biomasses of Descurainia pinnata and
      Lepidium lasiocarpum. The absence of C4 summer annuals in the high-nitrogen plots
      suggests that relatively high soil nitrogen adversely affected the summer
      annuals. Termite-free watered plots had higher soil moisture than the termite
      unwatered plots, but summer annuals were relatively abundant on the latter. Water
      amendments had a greater effect on the species abundances in the termite-free
      area than in the one with termites. In the area with termites, nitrogen
      amendments had a greater effect on species abundances. Species diversity and
      richness were affected by fertility as was species composition. This study
      demonstrates that we must understand patterns of soil nitrogen availability and
      processes affecting nitrogen availability in addition to water availability, in
      order to understand productivity and species composition of Chihuahuan Desert
      annual plants.

PMID- 29357140
TI  - Avian Fruit Removal: Effects of Fruit Variation, Crop Size, and Insect Damage.
AB  - Avian dispersal of seeds of the wild olive tree (Olea europaea var. sylvestris)
      was studied in Mediterranean shrubland, southern Spain. Fourteen species of small
      frugivorous birds in the genera Sylvia, Turdus, Sturnus, and Erithacus accounted
      for 97.4% of the fruits consumed by birds. The significance of each bird species
      as an Olea fruit consumer was closely related to its abundance in the area and
      was not associated with its dependence on the fruit for food; this resulted in a
      highly asymmetric interaction between the plant and its dispersers. Fruit
      production differed greatly between two consecutive seasons. During an extremely
      dry year most trees aborted their entire fruit crop just after flowering. During
      the 2nd yr, both flower production and fruit set increased, and this resulted in
      larger crops of ripe fruit. Most fruits that ripened (96.2% of the final-sized
      fruits) during the year of low fruit production were consumed by dispersers (X =
      93.9%), and incidence of fruit-damaging agents was low (6.0%). During the 2nd yr,
      fruit loss to the two main fruit predators, Dacus oleae (Tephritidae) and Prays
      oleae (Yponomeutidae), increased (X = 27.1%, range 1.1-52.3%). A satiation
      process took place during this year since fruit production exceeded the energy
      demand of the disperser assemblage, and this increased the potential for fruit
      loss to insect frugivores. Fruit removal by dispersers decreased (X = 52.4%), but
      the increase in fecundity during the 2nd yr for most of the trees compensated for
      this difference and resulted in a greater absolute number of seeds removed. Most
      variation in ripe fruit removal by birds was attributed to the interaction of
      dispersal-related plant traits with insect frugivores that determine post
      ripening fruit losses. The types of higher order interactions that result from
      the action of birds, the pulp-damaging fly, and the seed-eating moth larva may
      damp, or reverse, any selective effect of a single system component on plant
      traits related to seed dispersal.

PMID- 29357141
TI  - Body Size, Interspecific Interactions, and Use of Foraging Sites in Tits
      (Paridae).
AB  - In mixed-species flocks, the heavier tit species forage in the inner tree parts,
      while the smaller species exploit food items of the outer canopy. Using aviary
      experiments we studied the relative importance of two possible explanations for
      body size-foraging site correlation. The first hypothesis is that larger bodied
      tits are more efficient than smaller ones in exploiting the inner tree parts,
      while the reverse would be true in the outer canopy. However, the heavier
      species, the Willow Tit Parus montanus, was not more efficient in food searching
      in the inner tree parts than the smaller species, the Coal Tit Parus ater. The
      second hypothesis is based on interference competition with the socially dominant
      (heavier) species selecting the most profitable foraging sites, and forcing the
      smaller species to less rewarding places. In fact, in confrontation experiments
      only individuals of the smaller species changed their foraging sites in the
      presence of an individual of the other species in the aviary. In sum, body size
      influences social dominance relations and thereby relegates the smaller species
      to poorer foraging sites, but presumably gives them an advantage in exploitation
      competition via reduced energy demands for basal metabolism.

PMID- 29357142
TI  - Indirect Interactions Between Prey: Apparent Competition, Predator Aggregation,
      and Habitat Segregation.
AB  - Field experiments were performed to explore the nature of indirect interactions
      between two groups of ecologically distinct prey that occur on subtidal rocky
      reefs at Santa Catalina Island, California. Mobile gastropods (Tegula
      aureotincta, Tegula eiseni, and Astraea undosa) and sessile bivalves (mostly
      Chama arcana) share a common set of invertebrate predators (lobster Panulirus
      interrupts, cephalopod Octopus bimaculatus, and whelk Kelletia kelletii). The
      gastropods, which are secondarily preferred prey, principally occur on cobble
      reefs and less commonly on high-relief boulder reefs. Sessile bivalves and other
      species of favored prey are common on high-relief reefs and are rare or absent in
      cobble areas. The density of each predator species is greatest in high-relief
      areas containing abundant favored prey. Addition of bivalves to replicate cobble
      plots resulted in marked increases in predator density, relative to controls,
      because predators aggregated to areas containing favored prey. Greater densities
      of predators in the presence of experimentally added bivalves resulted in greater
      mortality and lower population densities of gastropods relative to controls.
      Conversely, mortality of Chama was higher where gastropods were common compared
      with cobble areas containing fewer gastropods. This occurred because the density
      of predators within a cobble reef, although low overall, was positively
      correlated with density of gastropods. Thus each group of prey was negatively
      affected by the presence of the other because each alternative prey increased the
      local density of predators. Such a doubly negative indirect interaction between
      prey, mediated by a shared predator, is known as a pparent competition; this is
      the first experimental demonstration of its existence. Because gastropods and
      bivalves are superior at withstanding predation in different habitats, shared
      predation and apparent competition may be sufficient mechanisms to maintain the
      pattern of habitat segregation displayed by these prey groups.

PMID- 29357143
TI  - Optimal Foraging in Seed-Harvester Ants: Computer-Aided Simulation.
AB  - This paper presents a computer-aided simulation of foraging behavior in seed
      harvester ant species. The simulation is based on regression studies of running
      speed, net cost of transport, worker size, load mass, and distance. The results
      show that, as a function of its size, each worker has a maximum transport yield
      and an upper load limit. For yields other than this maximum, those obtained by
      larger workers transporting small loads are less than those obtained if the same
      loads are transported by smaller workers. In addition, there are two possible
      load sizes for the same yield.

PMID- 29357144
TI  - Direct and Indirect Effects of Host-Plant Fertilization on an Insect Community.
AB  - Artemisia ludoviciana plants that received ammonium nitrate fertilizer were
      visually censused for all insects at  degrees  11 -d intervals from 30 June to 1
      September 1982. Community composition and species densities in fertilized plots
      were compared with those in control plots. Fertilization resulted in greater
      numbers of phloem- and seed-feeding insects and a concurrent increase in tending
      and patrolling by ants in fertilized plots. Chewing-insect densities did not
      respond uniformly to fertilization, and no chewing species exhibited the marked
      increase found in all of the sucking insects. Chrysomelid beetles and beetle
      damage decreased significantly in fertilized plots. A choice test between
      fertilized and control plants offered to beetles indicated that factors other
      than plant quality were responsible for the decrease in damage in fertilized
      plots. I suggest that increased densities of aggressive ants associated with
      honeydew-producing membracids and aphids caused this decline. Beetle damage was
      inversely correlated with aphid and membracid densities. Plots with ant nest had
      fewer plants with beetles and beetle damage than did those without ant nests. The
      indirect effect of increased ant densities from host-plant fertilization resulted
      in reduced levels of beetle damage to A. ludoviciana in fertilized plots. Since
      beetles removed large amounts of leaf area from A. ludoviciana in control plots,
      the indirect effect of higher ant densities should not be overlooked in assessing
      the general impact of fertilization on host plants.

PMID- 29357145
TI  - Utilization of Freshwater and Ocean Water by Coastal Plants of Southern Florida.
AB  - The coastal vegetation of southern Florida is undergoing dramatic changes due to
      the instability of the ocean water-freshwater boundary. These vegetation changes
      will be determined by the response of each particular species to saline ocean
      water, particularly whether it can use ocean water or not. In this study,
      isotopic data were used to determine the relative usage of freshwater or ocean
      water by plants in the Florida keys. The results indicate that, with some
      exceptions, plants toward the interior of the keys were using freshwater while
      those toward the edge were using ocean water. A plot of the hydrogen and oxygen
      isotopic composition of the plant water yielded a mixing line between typical
      freshwater values and those of ocean water. In general, the isotopic ratios of
      stem water for species found in hardwood hammocks were confined to the freshwater
      end of the line, followed by values of stem water from mangrove margin species.
      found in mangroves, however, had water with extremely variable isotopic ratios,
      ranging from values typical of ocean water to values typical of freshwater. This
      variability is consistent with the hypothesis that mangroves are fully capable of
      growing in freshwater, but are limited to saline habitats because of competitive
      exclusion by fast-growing glycophilic plants.

PMID- 29357134
TI  - Apelinergic System Structure and Function.
AB  - Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G
      protein-coupled receptor named the apelin receptor (AR/APJ/APLNR). Ligand-AR
      interactions have been implicated in regulation of the adipoinsular axis,
      cardiovascular system, and central nervous system alongside pathological
      processes. Each ligand may be processed into a variety of bioactive isoforms
      endogenously, with apelin ranging from 13 to 55 amino acids and apela from 11 to
      32, typically being cleaved C-terminal to dibasic proprotein convertase cleavage
      sites. The C-terminal region of the respective precursor protein is retained and
      is responsible for receptor binding and subsequent activation. Interestingly,
      both apelin and apela exhibit isoform-dependent variability in potency and
      efficacy under various physiological and pathological conditions, but most
      studies focus on a single isoform. Biophysical behavior and structural properties
      of apelin and apela isoforms show strong correlations with functional studies,
      with key motifs now well determined for apelin. Unlike its ligands, the AR has
      been relatively difficult to characterize by biophysical techniques, with most
      characterization to date being focused on effects of mutagenesis. This situation
      may improve following a recently reported AR crystal structure, but there are
      still barriers to overcome in terms of comprehensive biophysical study. In this
      review, we summarize the three components of the apelinergic system in terms of
      structure-function correlation, with a particular focus on isoform-dependent
      properties, underlining the potential for regulation of the system through
      multiple endogenous ligands and isoforms, isoform-dependent pharmacological
      properties, and biological membrane-mediated receptor interaction. (c) 2018
      American Physiological Society. Compr Physiol 8:407-450, 2018.

PMID- 29357146
TI  - Flowering, Shoot Production, and Vole Bark Herbivory in a Boreal Willow.
AB  - Different intensities of vole bark herbivory were simulated on the boreal willow
      Salix myrsinifolia-phylicifolia in field experiments, and plant responses were
      followed during 4 yr. Intermediate damage (every second stem barked) resulted the
      1st yr in a fourfold increase in the production of basal shoots per individual,
      and in the following years, a twofold increase in the number of catkins per
      intact stem compared with control willows. However, 1 yr after damage, the
      average number of seeds per individual was 21% lower than in control willows and
      seed germination was reduced 40%. Severe damage (all stems barked) caused a
      nearly 10-fold increase in the production of basal shoots the 1st yr and a
      reduction and delay of sexual reproduction. Mortality of damaged stems was high
      (100%), while genet mortality was < 5% in the group in which all stems were
      barked. Flowering in female willows was reduced more than in male willows, and
      males produced catkins on younger basal shoots than females. We suggest that in
      this system, where the principal herbivore fluctuates between years, compensatory
      reactions by damaged plants might be of particular benefit, as the period of
      growth following damage is more or less free from herbivores.

PMID- 29357147
TI  - Comparative Population Dynamics of Two Goldenrod Aphids: Spatial Patterns and
      Temporal Constancy.
AB  - Two aphid species, Uroleucon nigrotuberculatum and U. caligatum, that feed on the
      goldenrod Solidago altissima, are similar in life histories and feeding habits,
      but differ markedly in their spatial distribution and temporal variability. In
      this study, U. caligatum typically occurred in small colonies scattered
      throughout goldenrod fields, and its numbers remained relatively constant through
      time, whereas U. nigrotuberculatum occurred in dense colonies and exhibited
      greater fluctuations in population size. The aggregated spatial pattern of U.
      nigrotuberculatum resulted from both active aggregation of alates and lack of
      dispersal by apterae and nymphs. Field experiments in which colony size was held
      constant revealed that U. nigrotuberculatum enjoyed no clear reproductive
      advantage that might explain its greater tendency to outbreak. In addition, U.
      nigrotubercultatum was more susceptible to generalist predators (such as
      cantharid beetles, mirid bugs, and mites) than U. Caligatum. Aphid dispersion was
      then manipulated in the field to determine how the different spatial patterns of
      the two species influenced reproduction and mortality, and hence the relative
      tendencies of their populations to irrupt. Feeding in large colonies provided no
      reproductive advantage to either species. Aggregation did, however, enhance aphid
      survivorship when generalist predators were the main mortality agents. The
      advantage was reversed later in the season when the aphids' fungal pathogen was
      present; aggregation then led to a decrease in survivorship. Thus, aggregation
      allowed a numerical escape from generalist predators but also promoted fungal
      epidemics, so that the temporal variability in U. nigrotuberculatum populations
      was largely a consequence of its spatial distribution.

PMID- 29357148
TI  - The Enemies Hypothesis: Tritrophic Interactions and Vegetational Diversity in
      Tropical Agroecosystems.
AB  - The effects of vegetational diversity on the abundance of natural enemies of
      herbivores were studied in a traditional agroecosystem in tropical Mexico.
      Visitation patterns of parasitic Hymenoptera and densities of predators were
      compared between monocultures of squash and maize and mixed assemblages of maize,
      cowpea, and squash. The impact of parasitoid visitation was assessed by
      monitoring the percent parasitism of a target herbivore in the system: Diaphania
      hyalinata (L.) (Lepidoptera: Pyralidae), a cucurbit specialist. The "Enemies"
      hypothesis predicts a positive correlation between plant species richness and
      natural enemy abundance, which results in the regulation of herbivores at lower
      levels in diverse vegetation than in pure stands. The specific questions
      addressed in this study were: (1) are the major groups of natural enemies more
      abundant in patches of diverse vegetation than in monocultures?; (2) if so, does
      an increase in either abundance or diversity of natural enemies cause a
      concomitant increase in herbivore regulation?; (3) are the effects of
      vegetational diversity uniform over major enemy groups? The activity of
      hymenopteran parasitoids was affected by cropping pattern. Malaise trap captures
      of parasitoids in general, and of those species that attack D. hyalinata on
      squash, were consistently greater in tricultures than in squash monocultures, but
      were also greater in maize monocultures. Parasitism rates of eggs and larvae were
      higher on squash interplanted with maize and cowpea. These data partially support
      the "Enemies" hypothesis in explaining lower herbivore levels in diverse
      vegetation. However, the effects of diversity, per se, do not seem to be as
      important as the presence of maize in the system. The responses of natural
      enemies to vegetational diversity were not uniform. Most predators were not
      significantly influenced by cropping patterns, and some were more abundant in
      squash monocultures. The results of this study are discussed in terms of possible
      routes by which members of the third trophic level are influenced by plants in
      association.

PMID- 29357149
TI  - Disturbance and Predictability of Flowering Patterns in Bird-Pollinated Cloud
      Forest Plants.
AB  - The distribution and flowering patterns of hummingbird-pollinated plants were
      compared from July 1981 to June 1983 in three patch types in cloud forest at
      Monteverde, Costa Rica. Study plots were: (1) four recent, large (1100-2500 m2 )
      disturbances ("cutovers") produced by cutting vegetation, (2) six recent, smaller
      (200-600 m2 ) disturbances caused by treefalls, and (3) four plots (1600-1800 m2
      ) of canopied forest. Based on published literature dealing with communities that
      characterize different regimes of disturbance, we tested one assumption and two
      hypotheses. Assumption: Plant species composition differs among the three patch
      types. Hypothesis 1: Phenotypic specialization by plants for co-evolved
      interactions with hummingbirds will be lowest in large gaps, highest in forest,
      and intermediate in treefalls. Hypothesis 2: Predictability of flowering
      phenologies and nectar production will be lowest in large gaps, highest in
      forest, intermediate in treefalls. Neither the assumption nor the hypotheses were
      supported by the results. The patch mosaic in this cloud forest was not
      associated with major differences in species composition of bird-pollinated
      plants. Most species studied were self-compatible. Most abundant in cutovers were
      species with long corollas, relatively specialized for attracting long-billed
      hummingbirds. Species with short corollas, which can be visited by many
      hummingbird species and some insects, were most abundant in treefalls and forest.
      Variation in phenological patterns showed no consistent trends among patch types.
      Predictability of flower and nectar production tended to be greatest in
      treefalls, which are foci of concentrated flowering activity by all species.
      Discrepancies between our results and previous studies can be ascribed to two
      facts. (1) Much of the literature dealing with ecological consequences of
      disturbance has dealt with large-scale anthropogenic disturbances such as old
      fields of the eastern USA, whereas we studied small, natural, or quasi-natural
      disturbances. (2) Studies of forest disturbance have focused on the tree layer,
      whereas we studied the understory herbs, shrubs, and epiphytes. Natural
      disturbance usually involves death and replacement of one or more trees, whereas
      individuals of other life forms may persist through the disturbance.

PMID- 29357150
TI  - Dynamics of Nutrients and Leaf Mass in Central Himalayan Forest Trees and Shrubs.
AB  - Leaf dynamics, nutrient (N, P, K, Ca, and Na) changes, and retranslocation from
      the leaves of 13 species were investigated in four representative forest
      communities of the Central Himalaya, India. In evergreens of the temperate
      regions, with leaf longevities of several years, there is negligible movement of
      substances from leaves during the first year. For evergreens of the Central
      Himalaya, by contrast, loss of leaf mass beings in autumn and often continues
      until summer, when new leaves are formed. The decrease in leaf dry mass during
      this period was 12.3-34.1% of the maximum leaf mass. The concentration of N, P,
      and K decreased from the initial peak, stabilized as leaves matured, and declined
      markedly during senescence, while Ca and Na concentrations increased throughout
      the life-span of leaves. Leaf mass loss was positively related to most of the
      nutrient retranslocation percentages. There were significant correlations between
      retranslocation levels of many nutrients. The dominant canopy species (chir
      pine), which is adapted to infertile sites, showed conspicuously greater levels
      of nutrient retranslocation than species adapted to fertile sites (oaks).
      However, species of different growth forms occupying the same sites differed
      markedly in the extent of nutrient retranslocation.

PMID- 29357151
TI  - Comparative Life Histories of Holbrookia Maculata and Sceloporus Undulatus in
      Western Nebraska.
AB  - The life histories of the iguanid lizards Holbrookia maculata and Sceloporus
      undulatus were studied in western Nebraska during 1978-1984. The two species
      differ in their reproductive strategies and age-specific survival. The
      reproductive strategy of H. maculata is invariant from year to year. Yearlings
      consistently produced a single clutch and older females (>=2 yr) consistently
      produced two clutches. The reproductive strategy of S. undulatus is
      opportunistic. Clutch frequency of S. undulatus varied among years, ranging from
      1-3 for yearlings and 2-3 for older females. This variation in clutch frequency
      was a function of the length of the breeding season. Significant differences in
      the age-specific survivals of H. maculata and S. undulatus were found for
      juveniles and yearling females. In both cases, survival of H. maculata was
      greater. Despite differences in their life histories, H. maculata and S.
      undulatus are exposed to similar selective pressures in western Nebraska. Food
      does not appear to be limiting and mortality due to predation is low. Mortality
      is density-independent and is highest during the overwintering period.
      Differences in the reproductive strategies of H. maculata and S. undalatus are
      most likely due to their phylogenetic histories rather than to adaptation to
      different environments. The different reproductive strategies of the two species
      may account for differences in their age-specific survival. The high fecundity of
      yearling S. undulatus may explain its lower survival relative to H. maculata.
      Evidence for a cost of reproduction is provided by a negative relationship
      between clutch frequency of yearling S. undulatus and postreproductive survival.
      Because the response of lizards to specific environments may be constrained by
      their phylogenetic histories, comparison of life history strategies among
      syntopic species may not provide adequate tests of life history models. We
      conclude that identification of the mechanisms underlying variation in life
      history traits will most likely come from intraspecific comparisons.

PMID- 29357152
TI  - Wind Dispersal Distances in Dimorphic Achenes of Ragwort, Senecio Jacobaea.
AB  - A mark-recapture study of wind-dispersed achenes of Senecio jacobaeo conducted in
      western Oregon showed that the proportion of achenes dispersing a given distance
      varied significantly with changes in site (inland vs. coastal), surroundings
      (mown vs. unmown), height of release (0-50, 50-100, 100-150, 150-200 cm), time of
      release (early vs late in the season), direction of dispersal, and achene type
      (disk vs. ray achenes). Influences of height of release, direction, achene type,
      and time of release were strongly conditioned by site and surroundings. The
      majority of achenes dispersed very short distances. Of 53 301 achenes falling in
      the recapture area, 31% travelled only 1 m, 89% travelled 5 m or less, and none
      were collected > 14 m from the source. Thus, while it is theoretically possible
      for these wind-dispersed achenes to travel long distances, actual dispersal
      distances are short due to local conditions of humidity, wind, and vegetation
      structure.

PMID- 29357153
TI  - The Detection of Density-Dependence from a Series of Annual Censuses.
AB  - We report a distribution-free approach to the detection of density-dependence in
      the variation of population abundance, measured by a series of annual censuses.
      The method uses the correlation coefficient between the observed population
      changes and population size and proposes a randomization procedure to define a
      rejection region for the hypothesis of density-independence. It is shown that the
      use of the proposed statistic under the randomization approach is equivalent to
      the likelihood ratio test for a particular family of time series models. The
      randomization test is compared with two other recently proposed tests. Using
      computer-generated density-independent and density-dependent data, it is shown
      that, unlike the other tests, the randomization test is effective whether or not
      there is a marked trend in the observed data. Arguments are presented showing how
      one of the other two tests can be further improved. Caution is urged in the use
      and interpretation of any test for detecting density-dependence in census data
      because (a) the tests depend on assumptions about population processes, (b)
      errors of measurement may lead to spurious detection of density-dependence.

PMID- 29357154
TI  - A Spurious Correlation in an Interpopulation Comparison of Atlantic Salmon Life
      Histories.
AB  - We tested two hypotheses concerning geographical variation in Atlantic salmon
      (Salmo salar) life histories: (1) mean age at first reproduction is positively
      correlated with growth rate at sea and (2) within-population variation in age at
      first reproduction first increases and then decreases with latitude. Data on
      growth and age at first reproduction were compiled from 41 populations in eastern
      North America. Data reliability was checked by a redetermination of ages based on
      scale examination. The proportion of fish that were incorrectly aged was small (
      degrees 0.7%); however, aging errors were primarily of one kind; salmon that had
      previously spawned were misclassified as virgin fish of an older age class.
      Growth rate at sea was found not to be positively correlated with age at
      maturation. Schaffer and Elson's (1975) positive correlation between growth and
      age at first reproduction can be attributed to a subtle statistical artifact
      caused by aging errors. We also found that within-population variation of age at
      maturation was not related to latitude. We conclude that tests of life history
      theories should not assume constancy in life history traits, such as mortality,
      among populations.

PMID- 29357155
TI  - Flexible Life History Traits: Shifts by Scarlet Gilia in Response to Pollinator
      Abundance.
AB  - In response to reduced levels of pollinators and pollination, scarlet gilia,
      Ipomopsis aggregata, shift from their normal semelparous mode of reproduction to
      iteroparous reproduction. When pollinators were excluded, plants were 5.5 times
      as likely to produce an ancillary rosette as controls that received natural
      pollinator levels. Similarly, when flowers were removed to prevent fruit
      production, experimental plants were 7.8 times as likely to produce and ancillary
      rosette as unmanipulated controls exposed to natural levels of pollination.
      Although ancillary rosette production is correlated with both season and a
      decline in pollinators, when seasonality was experimentally eliminated as a
      variable, changes in pollinator abundance still resulted in a corresponding
      change in rosette formation. Results suggest that there is a threshold below
      which an individual can be expected to switch from semelparity to iteroparity;
      the threshold appears to be between 30 and 40% fruit set. Our experiments also
      demonstrate a trade-off between cloning and fruit production at the population
      level. Herbivory had no effect on these life history traits. Plants clipped to
      simulate natural herbivory by deer and elk showed no change in rosette formation
      relative to undamaged controls. These and other data demonstrate that pollinators
      are limiting and suggest that pollination is the primary factor involved in these
      life history trait shifts by scarlet gilia. Midseason shifts in life history
      traits permit plants to adjust to current lows in pollinator services by
      producing an ancillary rosette that can then flower in a subsequent year when
      pollinators may be less limiting.

PMID- 29357156
TI  - Hatching Asynchrony in American Goldfinches: An Experimental Study.
AB  - I examined Lack's (1954, 1968) hypothesis that asynchronous hatching is an
      adaptive response to food shortage during the breeding season by comparing growth
      and survival of nestlings in asynchronous and artificially created synchronous
      broods of American Goldfinches (Carduelis tristis). I also examined the effects
      of seasonal and environmental factors on nestling growth and survival and on
      hatching asynchrony. Nestlings in asynchronous broods were more likely to diverge
      in mass and did so at a faster rate than those in synchronous broods. The
      lightest nestlings of asynchronous broods grew more slowly than their heavier
      nestmates and than all nestlings in synchronous broods. Brood reduction occurred
      more frequently in asynchronous broods. Survival and growth rates decreased
      throughout the breeding season and during inclement weather. Hatching intervals
      increased during the season. When brood reduction or differential growth among
      nestmates occurred in asynchronous broods, suggesting that the energy available
      for growth was limiting, heavy nestlings in asynchronous broods grew
      nonsignificantly faster than heavy nestlings in concurrent synchronous broods.
      This trend implies that when insufficient food is delivered to nestlings,
      asynchronous hatching may provide a slight advantage for older nestlings. Growth
      rates of all nestlings, however, were greatest in highly synchronous broods.
      Explanations other than growth of young must be invoked to explain why extreme
      synchrony is not more common in goldfinches. I discuss constraints on the normal
      pattern of hatching asynchrony characteristic of this species. The proximate
      mechanism for differential feeding and brood reduction is discussed.

PMID- 29357157
TI  - AD HOC Editors of Manuscripts.

PMID- 29357158
TI  - Chemical Defense Against Diverse Coral-Reef Herbivores.
AB  - Five secondary metabolites from tropical marine algae and one related compound
      from an herbivorous sea-hare (Aplysidae) were coated, at approximately natural
      concentrations, onto the palatable seagrass Thalassia testudinum and placed on
      coral reefs where they could be eaten by the diverse group of herbivorous fishes
      that occur there. Laboratory feeding assays with the herbivorous sea urchin
      Diadema antillarum were also conducted. When compared to appropriate controls,
      the following terpenoid compounds significantly reduced the amount of Thalassia
      eaten by both Diadema and reef fishes: stypotriol, from the brown seaweed
      Stypopodium zonale; pachydictyol-A, which is produced by several genera of
      tropical (Dictyota and Dilophus) and warm-temperate (Pachydictyon and
      Glossophora) brown seaweeds; elatol, from the tropical red alga Laurencia obtusa;
      and isolaurinterol, which is produced by several tropical and warm-temperate
      species of Laurencia. Under very mild acid conditions, isolaurinterol is
      converted to a structurally similar compound, aplysin, found in high
      concentrations in sea-hares that feed on isolaurinterol-containing Laurencia
      species. Aplysin did not deter feeding by either type of herbivore. Cymopol, a
      terpenoid bromohydroquinone from the green alga Cymopolia barbata, significantly
      reduced feeding by reef fishes but significantly stimulated feeding by Diadema.
      Pharmacological and crude bioactivity tests suggest that several of these
      compounds function as generalized toxins. However, these generalized laboratory
      assays are not necessarily good predictors of how compounds will affect feeding
      by herbivores. For example, pachydictyol-A and stypotroil were equally effective
      at deterring fishes and Diadema, even though pachydictyol-A shows almost no
      bioactivity in laboratory assays while stypotriol and its oxidation product,
      stypoldione, are very bioactive. Herbivory on coral reefs is more intense than in
      any other habitat studied and the diversity of herbivore types is high. It
      appears that this intense grazing has provided strong selection for seaweeds that
      synthesize unique secondary metabolites that significantly reduce the consumption
      of plants exposed to attack by a diverse group of reef herbivores.

PMID- 29357159
TI  - Coral Reef Recovery on Guam (Micronesia) After Catastrophic Predation by
      Acanthaster Planci.
AB  - At Tanguisson Reef, Guam, in 1968-1969 a population explosion of the coral-eating
      sea star Acanthaster planci devastated the coral community. In the wake of this
      predation, coral species richness, density, and cover were drastically reduced,
      and the species composition was altered. In two of three reef zones examined, <
      1% coral cover remained. At the time of disturbance, some considered the
      magnitude of this and similar Acanthaster disturbances unprecedented, and
      predicted long recovery times because reefs were viewed as mature, stable
      communities. This major disturbance offered an opportunity to study the processes
      and rate of community recovery. Using the data from previous studies in 1970,
      1971, and 1974, and my data from 1980-1981, I present a long-term analysis of
      coral community development. I have focused on coral recruitment, survivorship,
      and species settlement patterns in relationship to the remnant surviving
      population. The preference of Acanthaster planci for certain prey (e.g.,
      Montipora and Acropora) shifted the species composition to one in which
      nonpreferred prey predominated (e.g., Porites and Leptastrea). The predominance
      of nonpreferred prey was short-lived, and by 1980, preferred prey were the
      primary colonists of two zones. The three biological zones (reef front, submarine
      terrace, and seaward slope) had their own characteristic species assemblages soon
      after the disturbance. Nonrandom recruitment or survival of juvenile corals
      (diameter <= 4 cm) established these zones. Although the percentage of juvenile
      corals fell throughout the survey, their highest density was reached after adult
      colonies were established. In 1980, of the 34 species examined, 79% showed a
      significant coefficient of association between adult and juvenile conspecifics.
      This association caused clumped species dispersion patterns to develop within
      zones. As the result of recruitment, species diversity rose from 84 species in
      1970 to 154 species in 1981. As surviving corals and new recruits developed, the
      distribution of coral growth forms became more diversified. There was a drastic
      increase in coral cover (e.g., submarine terrace zone, 0.9% in 1970 to 65% in
      1981). This increase in cover corresponded to an increase in size and number of
      the coral colonies In 12 yr, species richness, cover, and composition reached or
      exceeded measurements of comparable reefs before the disturbance. The recovery
      occurred faster than predicted by a stable equilibrium model because long-term
      successional changes were not required. Recovery was accelerated because
      Acanthaster did not destroy the structural integrity of reef framework. This
      rapid recovery from a natural disturbance demonstrates that some coral
      communities have a greater resilience than was once believed.

PMID- 29357161
TI  - Chemical Defense Against Different Marine Herbivores: Are Amphipods Insect
      Equivalents?
AB  - The Structurally similar diterpenoid alcohols pachydictyol-A and dictyol-E are
      produced by the brown seaweed Dictyota dichotoma. This seaweed and several
      related species that also produce these compounds are known to be relatively low
      preference foods for tropical fishes and urchins. We evaluated the effect of
      various concentrations of these compounds on feeding by the three common types of
      herbivores that co-occur with Dictyota in coastal North Carolina. Fish (Diplodus
      holbrooki), sea urchins (Arbacia punctulata), and a mixed species group of
      gammarid amphipods were offered pieces of the palatable seaweed Gracilaria
      tikvahiae coated with either (1) dictyol-E or pachydictyol-A dissolved in diethyl
      ether or (2) diethyl ether alone. Dictyol-E significantly reduced consumption by
      fish and urchins at concentrations of 0.5 and 1.0% of algal dry mass, but had no
      effect on amphipod grazing. Pachydictyol-A significantly reduced fish grazing at
      the relatively high concentrations of 1.0 and 1.3% of plant dry mass; at 0.5% it
      tended to decrease grazing, but the effect was not significant (P = .07).
      Pachydictyol-A had no effect on urchin grazing and significantly increased
      amphipod grazing. When Pachydictyol-A was fed to fish as 1.0% of food dry mass,
      their growth rate was reduced by a significant 48%. In feeding preference
      experiments with several seaweeds, Dictyota ranks low for fish and urchins but
      high for amphipods. This is consistent with the hypothesis that the secondary
      metabolites produced by Dictyota play a major role in determining its
      susceptibility to herbivores. The ability of amphipods to circumvent the chemical
      defenses (Dictyota, and the fact that the two species of algae most readily
      consumed by amphipods (Codium and Dictyota) were the two species least readily
      consumed by fish, suggest that predation and herbivory by fishes may be major
      factors selecting for amphipods that can live on, and eat, seaweeds that are
      unpalatable to fishes. Amphipods that fed on Dictyota did not appear to sequester
      the Dictyota metabolites; when exposed to fish predation, Dictyota-fed amphipods
      were eaten as readily as amphipods that had fed on an alga with no defensive
      chemistry. Tubicolous amphipods and other small marine herbivores that may spend
      significant portions of their lives on only a few plants my be under very
      different evolutionary constraints than the larger, more mobile herbivores that
      commonly moved between many plants. Several characteristics of these smaller,
      less mobile, and much less studied, marine herbivores suggest that they may be
      ecologically similar to terrestrial insects and may play a large, but presently
      unappreciated, role in structuring marine plant communities.

PMID- 29357162
TI  - Seedling Recruitment Strategies in Obligate-Seeding and Resprouting Banksia
      Shrubs.
AB  - Banksia ericifolia is killed by fire and so depends upon seeds for persistence.
      In contrast, B. oblongifolia can persist after fire by resprouting from protected
      buds, as well as by recruiting seedlings. These serotinous species coexist in the
      fire-prone scrublands of the Sydney Basin. Here we report experiments that
      compared seed release from cones retained in the canopy, seed germination, and
      seedling establishment in these two species. B. oblongifolia seeds were released
      more quickly than B. ericifolia seeds after a fire, and B. oblongifolia follicles
      opened and shed seeds after exposure to lower temperatures than those of B.
      ericifolia. B. oblongifolia seeds germinated more quickly than those of B.
      ericifolia. The relative growth rates and leaf mass ratios (mean ratio of leaf
      dry mass to plant dry mass over sequential harvests) of the two species did not
      differ. Root : shoot ratios were significantly large and biomass allocation to
      roots was faster in B. oblongifolia seedlings. B. ericifolia seedlings survived
      low and intermediate levels of droughting better than B. oblongifolia under
      greenhouse conditions. In a field experiment in which water was not limiting,
      large B. oblongifolia seedlings had the highest survival rate. These results
      suggest that selection has acted on B. ericifolia to minimize the chance of zero
      seedling survival by distributing the risks over more than one germination
      episode. There was no consistent evidence to support the hypothesis that
      selection on this species has increased its probability of seedling survival
      during any one germination opportunity relative to its congener.

PMID- 29357163
TI  - Experimental Analysis of the Grazing Interaction Between a Mayfly and Stream
      Algae.
AB  - The interaction between the grazing mayfly Ameletus validus and periphyton in a
      small, northern California stream was examined by manipulating the density of the
      mayfly in flow-through plexiglass channels. Containing natural cobble substrate
      and located in situ, the channels established an initial gradient of A. validus
      at 0, 0.5, 1, and 4 times the average density of the mayfly in Barnwell Creek.
      After 23 d, A. validus significantly depressed periphyton standing crop: ash-free
      dry mass (AFDM) at the 0, 0.5, 1, and 4 N grazer densities was 5.067 +/- 1.389
      (se), 1.829 +/- 0.173, 1.741 +/- 0.325, and 1.009 +/- 0.199 g/m2 (ANOVA: P <
      .01). The mayfly also influenced two structural attributes of the periphyton,
      increasing the amount of chlorophyll a per unit biomass and decreasing the
      relative contribution of the loose, upper layer to total periphyton biomass.
      Principal component analysis of algal relative abundances contrasted the effect
      of grazing on two groups of diatoms. A group of species found primarily in the
      loose layer of periphyton (Nitzschia spp., Surirella spiralis, Cymatopleura
      elliptica, and Navicula cryptocephala) was disproportionately reduced in
      abundance, while an adnate group (Gomphonema clevei, Achnanthes minutissima,
      Synedra ulna, Rhoicosphenia curvata, and an undescribed species of Epithemia)
      increased its relative abundance with increasing grazing pressure. The decline in
      relative abundance of the loose layer diatoms did not appear to result from
      selective consumption by A. validus, but may have been mediated by a reduction of
      inorganic sediment in the periphyton by A. validus. Inorganic sediment was highly
      correlated with the relative abundances of the loose layer group of diatoms, a
      group of species that are adapted for locomotion on sediment substrates. A.
      validus growth in the experimental channels was strongly density dependent.
      Growth in length over 23 d for the 0.5, 1, and 4 N treatments was 2.24 +/- 0.17,
      1.80 +/- 0.23, and 1.15 +/- 0.25 mm (ANOVA: P < .01). The significantly greater
      growth of A. validus at subnormal densities in the experimental channels
      suggested that the A. validus population in Barnwell Creek was food-limited.

PMID- 29357164
TI  - Determinants of Competitive Success in Clethrionomys Rufocanus.
AB  - This study introduces a new approach to identify determinants of competitive
      success in small mammals. An experimental population of Clethrionomys rufocanus
      consisting of laboratory-raised individuals with known origin and life history
      was introduced to a realistic competitive situation in the field. Successful
      females could be distinguished from nonsuccessful females on the basis of four
      individual attributes measured 25 d after they were released on the study plot,
      whereas males could not. The most consistent determinant of competitive success
      seemed to be the sex ratio of the litters in which females were born. Successful
      females originated from litters with a strongly female-biased sex ratio. These
      results are considered in the light of recent research on the consequences of
      prenatal conditions on female social behavior.

PMID- 29357165
TI  - Biomass and Nutrient Accumulation During Stand Development in Wyoming Lodgepole
      Pine Forests.
AB  - Accumulation rates of biomass and nutrients during stand development in lodgepole
      pine (Pinus contorta ssp. latifolia [Engelm. ex Wats.] Critchfield) forests were
      calculated using dendrochronological reconstructions of biomass in conjunction
      with information on detrital immobilization of nutrients. Dead wood, forest
      floor, and live tree Including root) biomass were examined. Maximum total biomass
      accumulation rates of 2.5-3.2 Mg degrees ha-1  degrees yr-1 were reached between
      ages 40 and 60 yr in even-aged stands, but an uneven-aged stand did not achieve a
      maximum accumulation rate (1.5 Mg degrees ha-1  degrees yr-1 ) until after 80 yr
      of development. The results suggest (1) a major role for forest floor detritus in
      the retention of N, P, Ca, and Mg; (2) the importance of living vegetation for K
      retention; and (3) the fundamental differences in biomass and nutrient dynamics
      between even-aged stands that develop after fire and stands that develop through
      gradual invasion of a meadow.

PMID- 29357166
TI  - Regulation of Lake Primary Productivity by Food Web Structure.
AB  - We performed whole-lake manipulations of fish populations to test the hypothesis
      that higher trophic levels regulate zooplankton and phytoplankton community
      structure, biomass, and primary productivity. The study involved three lakes and
      spanned 2 yr. Results demonstrated hierarchical control of primary production by
      abiotic factors and a trophic cascade involving fish predation. In Paul Lake, the
      reference lake, productivity varied from year to year, illustrating the effects
      of climatic factors and the natural dynamics of unmanipulated food web
      interactions. In Tuesday Lake, piscivore addition and planktivore reduction
      caused an increase in zooplankton biomass, a compositional shift from a
      copepod/rotifer assemblage to a cladoceran assemblage, a reduction in algal
      biomass, and a continuous reduction in primary productivity. In Peter Lake,
      piscivore reduction and planktivore addition decreased zooplanktivory, because
      potential planktivores remained in littoral refugia to escape from remaining
      piscivores. Both zooplankton biomass and the dominance of large cladocerans
      increased. Algal biomass and primary production increased because of increased
      concentrations of gelatinous colonial green algae. Food web effects and abiotic
      factors were equally potent regulators of primary production in these
      experiments. Some of the unexplained variance in primary productivity of the
      world's lakes may be attributed to variability in fish populations and its
      effects on lower trophic levels.

PMID- 29357167
TI  - Proximate and Ultimate Roles of Food Amount in Regulating Egret Sibling
      Aggression.
AB  - In facultatively siblicidal bird species, the amount of food delivered by parent
      birds to their young ("food amount") has been assumed to be both an important
      proximate and ultimate cause of fatal aggression. The proximate "Food Amount
      Hypothesis" (FAH) contends that sibling aggression will vary inversely with the
      quantity of food delivered by the parents, presumably mediated by chick hunger.
      At the ultimate level, food shortages are expected to influence whether the
      combined effects of aggression and food control by older siblings will be fatal
      to the youngest brood member(s). We evaluated the effects of food amount on
      aggression and survival in facultatively siblicidal Ardeidae: (1) Sibling
      aggression in unmanipulated broods of Great Egrets (Casmerodius albus) and Great
      Blue Herons (Ardea herodias) did not decline with increasing amounts of food, as
      had been predicted; indeed, this relationship may even be weakly positive. (2) In
      egret broods, the strongest predictors of total brood success were competitive
      vigor of the youngest sib and fighting rate. (3) Wild egret broods whose food
      amount was experimentally doubled did not reduce fighting rates, but experienced
      significantly lower brood reduction than control broods. (4) Captive egret broods
      whose food amount was experimentally decreased did not increase fighting rates,
      but suffered significantly more brood reduction than control broods. (5) In the
      wild, food amount appears not to be a sufficiently stable parameter on which to
      base prudent sib-aggression strategies. We conclude that food amount has little
      direct influence on fighting behavior in these birds, though it consistently
      influences chick survival. Thus the proximate effects of this ecological variable
      must be divorced from its ultimate role, at least in species such as these
      ardeids and in obligate-siblicidal species. However, the FAH may well account for
      sib-fighting variation in other facultatively siblicidal birds, such as Blue
      footed Boobies (Sula nebouxii), Black-legged Kittiwakes (Rissa tridactyla),
      Ospreys (Pandion haliaetus), and South Polar Skuas (Catharacta maccormicki). It
      is predicted that sibling aggression will be food-amount dependent in species
      whose food fluctuations are relatively slow. An attempt to manipulate prey
      monopolizability (bolus size) in captive Great Egrets was unsuccessful, either
      because sib aggression in the laboratory was so inflated as to swamp prey-size
      effects or because this species simply lacks sufficient developmental flexibility
      in its intrabrood fighting behavior. If the latter were true, it would reveal a
      striking difference between Great Egrets and Great Blue Herons, which have shown
      considerable (adaptive) plasticity in this regard.

PMID- 29357168
TI  - Comparative Analyses of Carbon Dynamics in Native and Cultivated Ecosystems.
AB  - Plant productivity, litter decomposition rates, and soil organic matter
      accumulation for winter wheat and for unbroken tallgrass prairie in Central
      Missouri were analyzed and compared. As measured in this 3-yr study, annual
      production of dry matter above- and belowground for the cultivated system
      averaged slightly higher than that for the natural vegetation burned every 3-4
      yr. Prairie was characterized by greater year-to-year fluctuation of
      productivity, which in some years exceeded productivity of the cultivated system.
      More litter and structural biomass older than 1 yr occurred in the prairie,
      reflecting the perennial nature of the root system. Principal pathways of carbon
      transfer in both ecosystems were modeled, and mean residence time in major
      storage compartments estimated. Combined CO2 losses from above- and belowground
      litter decay, expressed as a percentage of total soil respiration, were twice as
      great under wheat as for native prairie. A relatively greater fraction of net
      primary production was available for synthesis of soil organic matter in native
      prairie. Under equilibrium conditions, decomposition constants for this
      compartment, however, were similar. Contrasts in community structure and
      phenology, seasonal dynamics of litter decay, and levels of soil disturbance are
      suggested influences affecting transfer and storage characteristics.

PMID- 29357169
TI  - Habitat Selection Under Predation Hazard: Test of a Model with Foraging Minnows.
AB  - Animals commonly choose among habitats that differ both in foraging return and
      mortality hazard. However, no experimental study has attempted to predict the
      level of increase in resources, or the decrease in mortality hazard, which will
      induce a forager to shift from a safer to a more hazardous (but richer) foraging
      area. Here we present and test a model that specifies the choice of foraging
      areas ("habitats") that would minimize total mortality risk while allowing
      collection of some arbitrary net energy gain. We tested the model with juvenile
      creek chubs (Semotilus atromaculatus) in an experimental field stream in which
      the foragers could utilize a foodless refuge and choose between two foraging
      areas that differed in experimentally manipulated resource densities (Tubifex
      spp. worms in sediments) and mortality hazard (adult creek chubs). For the case
      tested, the model specified a simple rule: "use the refuge plus the site with the
      lowest ratio of mortality rate (MU) to gross foraging rat (f)," i.e., "minimize
      MU./f." Independent prior measurements of mortality hazard (as a function of
      predator density) and gross foraging rate (as a function of resource density)
      allowed us to predict the resource level in the more hazardous foraging site that
      should induce a shift from the safer to the more hazardous site. The chubs'
      preferences in subsequent choice experiments agreed well with the theoretical
      predictions. The "minimize MU/f" rule (deaths per unit energy), perhaps in
      modified form, provides a simple alternative to the "maximize f" (energy per unit
      time) criterion that applies to long-term rate maximization when predation hazard
      does not differ among choices.

PMID- 29357170
TI  - Breeding Birds of Isolated Woodlots: Area and Habitat Relationships.
AB  - We investigated breeding bird communities of isolated woodlots (1.8-600 ha) in
      east-central Illinois during three summers (1979-1981) to compare the influence
      of area and habitat on community structure. Woodlots supported from 9 to 43
      species and composition was relatively constant among years. Ecological
      generalists dominated small woodlots, while more specialized species increased in
      importance with area. Area accounted for most variation (86-98%) in total species
      number in each year and the species-area relationship did not change
      significantly among years. The amount of variance accounted for by area was
      greater than in previous studies. Neither habitat nor woodlot isolation explained
      significant additional variation in total species richness after area. Area
      accounted for most variation in number of species in different migratory and
      breeding habitat categories, except for short-distance migrants, which correlated
      most strongly with habitat. Variation in habitat was not related to woodlot area
      and habitat accounted for additional variation in bird species numbers in most
      cases. Abundances of one-third to one-half of species examined correlated with
      woodlot area, but a greater proportion (66-72%) were influenced more strongly by
      habitat variables. Results from Illinois support previous conclusions that
      species that breed in forest interior habitat and winter in the tropics are most
      likely to be adversely affected by a reduction in forest habitat. Results also
      show that bird communities in isolated tracts of forest are not random
      assemblages, but rather that species found in smaller woodlots are subsets of
      species found in larger forests.

PMID- 29357171
TI  - Clonal Integration and Population Structure in Perennials: Effects of Severing
      Rhizome Connections.
AB  - Short rhizomes in perennial plants lead to compact genet architecture and
      populations consisting of monoclonal patches. Long rhizomes lead to spreading
      genets and polyclonal patches. To test if shoot integration within genets was
      higher in the first case than in the second, we compared shoots of connected
      genets to artificially disconnected shoots for three Aster species (spreading
      genets), Solidago canadensis (compact genets), and S. gigantea (intermediate)
      grown in high and low density, pure and mixed sands. Severing rhizome connections
      stimulated plant growth in S. canadensis but had only small effects on growth in
      Aster and S. gigantea. In low density, the production of new rhizome and shoot
      modules of S. canadensis, and to a lesser degree of S. gigantea, was restricted
      by integration. Aster performed better and S. canadensis worse in mixed than in
      pure stands. Intact connections did not increase the competitive ability of s.
      canadensis grown in mixture. Shoots of S. canadensis, but not of S. gigantea and
      Aster, were more variable if connected in pairs than if isolated (or connected in
      fours). The results confirm the prediction that integration increases with
      increasing genet compactness, i.e., Aster < S. gigantea < S. canadensis. They
      further indicated that destroying physical connections in integrated genets may
      decrease between-shoot competition rather than between-shoot cooperation.
      Ecological consequences of high vs. low clonal integration in perennial plants
      are discussed.

PMID- 29357172
TI  - Leaf Demography and Clonal Growth in Female and Male Rumex Acetosella.

PMID- 29357173
TI  - Ecological Consequences of an Exceptionally Strong El Nino Event on Darwin's
      Finches.
AB  - We studied the effects of heavy rainfall associated with the El Nino event of
      1982-1983 on the demography of Darwin's Ground Finch (Geospizinae) populations
      and their resources on Isla Daphne Major, Galapagos. Total rainfall during this
      period (1359 mm) was 10 times the previously recorded wet season maximum. Most
      plant species responded by dramatically increasing seed production; total seed
      biomass increased by an order of magnitude, and small seed biomass increased in
      relative abundance, from 20% of total seed biomass before 1983 to >80% at the
      peak of the event. Caterpillars, the main food used by finches while breeding,
      also became extremely abundant. Ground finch species, mainly the Medium Ground
      Finch (Geospiza fortis) and the Cactus Finch (G. scandens), responded to the
      increase in food supply by breeding repeatedly. Females of both species produced
      up to 10 clutches of eggs; normally they produce 1-5 clutches. The most
      productive female fortis and scandens individuals fledged 25 and 19 young,
      respectively. Some birds born at the beginning of the season bred successfully
      before the end. Clutch sizes were scarcely larger than before and overall
      fledging success per nest was lower than in a normal breeding season. The large
      number of young produced resulted in (1) increases in population sizes of both
      species by a factor of four, (2) a dramatic skew in the age structure of both
      species, with birds born in 1982-1983 making up >75% of each population in
      January 1984, and (3) >50% of the lifetime fledgling production of females born
      in 1978 occurring in this breeding season. Individuals of both species immigrated
      from nearby islands, and a nonresident species, the Large Ground Finch (G.
      magnirostris) immigrated and bred on the island. Severe El Nino events have
      important ecological and evolutionary effects on these birds. For example, the
      high proportion of lifetime reproductive success contributed under exceptionally
      favorable conditions may have influenced the evolution of life history
      characteristics in the finches. Overall, our results support the view that rare
      events can have a major influence on key population processes in long-lived birds
      living in temporally varying environments, and that long-term studies are
      necessary to detect such effects.

PMID- 29357174
TI  - Distribution of Seeds in Sonoran Desert Soils: Implications for Heteromyid Rodent
      Foraging.
AB  - We used a hierarchical sampling design to investigate temporal and spatial
      patterns of variation in the topsoil seedbank at a site on the Santa Rita
      Experimental Range, 50 km south of Tucson, Arizona. Replicate sets of contiguous
      4  degrees  4 cm samples to 2 cm depth ("transects") were collected three times
      per year, from 1980 to 1983, from four microhabitats that are differentiated by
      desert heteromyid rodents: large and small open spaces, under canopies of large
      shrubs, and under canopies of small trees. We also analyzed texture and organic
      content of soils from the four microhabitats. Seeds from 54 plant taxa were
      encountered, most of them rare. Average seed mass across species was 1.28
      mg/seed, but because tiny seeds were most numerous, the abundance-weighted
      average was 0.16 mg/seed. Total seed abundance was highly variable, ranging from
      0 to 256 seeds and from 0 to 146 mg per sample. The fourfold temporal variation
      in mean mass or number of seeds per sample was largely due to between-year rather
      than between-season effects. Seed standing crops were positively correlated with
      rainfall during the previous 6-mo rainy period, and were lowest in fall and
      winter of 1982 after 2 yr of poor winter rains. Mean seed number per sample,
      which reflects primarily abundance of tiny seeds, did not vary among
      microhabitats. Mean per-sample seed mass, which reflects abundance of the large
      seeds eaten by rodents, did vary among microhabitats, however, with values being
      higher under shrubs and trees than in open spaces. The low mean abundance in open
      spaces was due more to a high frequency of seedless samples than to low maximum
      per-sample abundance. Hence, profitable seed patches do occur in open spaces, but
      are rarer than under shrubs or trees. Within microhabitats there was significant
      variation among replicate transects and among samples within transects. On a
      local scale, seeds occurred in patches 12 cm in diameter in all microhabitats and
      sampling periods. Seed species composition varied seasonally and among
      microhabitats, and there was an overall correlation between seed and adult
      microhabitat distribution for spring ephemerals. Soil from open spaces was finer
      and had lower organic content than that under shrub or tree canopies. Our results
      suggest that the resource upon which desert granivores depend is highly variable
      in time and space. Microhabitat is one of the most conspicuous sources of
      variation, and heteromyid rodent species differ in use of those microhabitats
      (open spaces vs. areas under canopies of perennial plants) that differ most
      noticeably in seed abundances, species composition, and soil characteristics.

PMID- 29357175
TI  - Larval Dispersion and Survivorship in a Leaf-Mining Moth.
AB  - We observed and quantified leaf miner distribution on Quercus geminata in order
      to determine its relation to leaf abscission and the effects of leaf abscission
      on larvae. A leaf-mining moth, Stilbosis quadricustatella, exhibited a clumped
      distribution of mines among leaves of the evergreen oak Quercus geminata. Mines
      tended to be on large, peripheral, and undamaged leaves so that leaves were often
      multiply minded. Mined leaves, especially those with multiple mines, tended to
      abscise early. Unless miners in an abscised leaf were very near to pupation,
      abscission killed them. Premature leaf fall was by far the largest source of
      larval mortality for this moth. A preliminary analysis suggested that the
      clumping of miners was no more favorable to the tree (in terms of number of
      leaves abscised early) than to the insect.

PMID- 29357176
TI  - Plant Community Diversity, Herbivore Movement, and an Insect-Transmitted Disease
      of Maize.
AB  - Field experiments were carried out in Nicaragua to examine the influence of plant
      community diversity, plant density, and host plant quality on the spread of an
      insect-transmitted plant pathogen. Population levels of the corn leafhopper
      Dalbulus maidis, which transmits the corn stunt spiroplasma to maize, were
      monitored in four experimental communities; low-density maize monoculture, high
      density maize monoculture, two-species (maize/bean) polyculture, and multispecies
      (maize/weeds) polyculture. Leafhopper abundance per plant and the incidence of
      corn stunt were lower in high-density maize monocultures than in low-density
      monocultures. Increasing plant diversity by intercropping with nonhost species
      such as beans or weeds also led to lower leafhooper abundance and decreased
      disease incidence, but the effect was not enhanced as additional nonhost species
      were added to the community. Manipulating host plant quality by increasing
      nitrogen fertilization resulted in higher leafhopper densities at higher nitrogen
      levels. To explore the role of vector movement in disease spread, leafhopper
      movement rates and emigration were estimated by observing changes in the spatial
      gradients of leafhopper densities over time. This method of movement analysis
      requires neither marking the insects nor releasing them at a single point, and
      thus reduces the extreme disturbance caused by traditional mark-release
      techniques. The analysis indicated that leafhopper movement rates were lowest in
      the polycultures. In particular, across-row movement was strikingly inhibited in
      the bean polyculture. This polyculture also had the highest rates of emigration.
      These results indicate that plant quality, density, and diversity significantly
      affect the spread of corn stunt through their effects on the abundance and
      movement behavior of the corn leafhopper. These factors could be manipulated in a
      program of cultural control for corn stunt in maize fields in tropical America.

PMID- 29357177
TI  - Local Geomorphology as a Determinant of Macrofaunal Production in a Mountain
      Stream.
AB  - By comparing distributions of functional group production among different
      habitats in an Appalachian mountain stream, the influence of site-specific
      geomorphology upon the overall functional group composition of the animal
      community was demonstrated. By replicated monthly sampling, substrate particle
      size distributions, current velocity, standing crops of benthic organic matter,
      and production of macrofauna were measured in each of three principal habitats:
      bedrock-outcrop, riffle, and pool. Samples were taken at randomly assigned
      locations and the relative number of samples taken from each habitat was assumed
      to be proportional to the area of the habitat within the stream. These
      proportions were used to weight production measured in each habitat and the
      resulting values were summed to obtain production per unit area of average stream
      bed. The bedrock-outcrop habitat was characterized by high material entertainment
      and export as indicated by significantly higher current velocities and lower
      standing crops of detritus compared to the riffle and pool habitats. Pools were
      sites of low entertainment and high retention of organic matter as demonstrated
      by significantly lower current velocities and higher accumulations of detritus
      than other habitats. The riffle habitat was intermediate to the bedrock-outcrop
      and pool habitats in all parameters measured. Annual production of collector
      filterers was highest in the bedrock-outcrop (ash-free dry mass 1920 mg/m2 ),
      followed by riffle (278 mg/m2 ) and pool (32 mg/m2 ). Although constituting only
      19% of the stream area, the bedrock-outcrop habitat contributed 68% of the
      habitat-weighted collector-filterer production. Annual production of shredders
      was highest in pools (2616 mg/m2 ), followed by riffles (1657 mg/m2 ) and bedrock
      outcrop (579 mg/m2 ). The pool habitat, constituting 23% of stream area,
      contributed 36% of shredder production. Annual production of scrapers was highest
      in the riffle habitat (905 mg/m2 ), followed by bedrock-outcrop (517-mg/m2 ) and
      pool (238 mg/m2 ). Riffles constituted 58% of total stream area and were the
      source of 77% of the habitat-weighted scraper production. Annual production of
      engulfing predators was greatest in the pool habitat (2313 mg/m2 ), followed by
      riffles (1765 mg/m2 ) and bedrock-outcrop (687 mg/m2 ). The relatively lower
      production of engulfing predators in the bedrock-outcrop habitat reflects a
      functional shift in mode of resource acquisition by predators, with predaceous
      collector-filterers (Arcto-psychinae: Trichoptera) predominating in the bedrock
      outcrop. Collector-gatherer production was more evenly distributed, with the
      bedrock-outcrop, riffle, and pool habitats each contributing 14, 54, and 33% to
      the habitat-weighted production, respectively. Unlike all other functional
      groups, this distribution was not significantly different from the distribution
      of stream area among habitats and reflected lack of dependence on specific
      physical attributes of the local environment for access to food by members of
      this functional group. Local geomorphology determined the diversity and spatial
      distribution of bedrock-outcrops, riffles, and pools in the study stream. In
      turn, the functional structure of the macrofauna, when viewed holistically, was
      the result of the integration of the relative contributions of each habitat type
      of total stream area. Total habitat-weighted annual production in the study
      stream was estimated at 5093 and 1921 mg/m2 for primary and secondary consumers,
      respectively. The distribution of habitat-weighted production among functional
      groups was: collector-gatherers (39%), followed by shredders (225), engulfing
      predators (22%), scrapers (13%), and collector-filterers (8%). This functional
      structure agrees favorably with current conceptual models of head water streams
      draining forested catchments.

PMID- 29357178
TI  - A Large-Scale Comparison of Factors Influencing Phytoplankton Abundance in
      Rivers, Lakes, and Impoundments.
AB  - We analyzed two large data sets (the National Stream Water Quality Accounting
      Network and the National Eutrophication Survey) to compare quantitatively the
      ecological structure and function of rivers, river impoundments, and natural
      lakes on a broad scale. Discriminant analysis with physical-chemical variables
      separated these three types of aquatic systems along a composite gradient that
      correlated with water residence time (r = 0.7), drainage area (r = 0.7), water
      depth (r = 0.6), stream flow (r = 0.6), and water clarity (r = 0.4). Natural
      lakes and rivers occupied opposite ends of this gradient, and reservoirs, on
      average, were intermediate, but natural lakes and impoundments overlapped
      extensively and did not form a useful dichotomy. Regression analysis showed algal
      abundance per unit phosphorus increasing in the sequence: rivers < impoundments <
      natural lakes, which paralleled intergroup differences in residence time. Algal
      abundance per unit phosphorus did not differ significantly among these three
      system types when systems with similar residence times were compared. Our results
      indicate that water residence time is a useful system-level index that has
      similar ecological implications for rivers, lakes, and reservoirs.

PMID- 29357179
TI  - Interspecific Competition and the Abundance of Nest Sites: Factors Affecting
      Sexual Selection.
AB  - The abundance of suitable nest sites and competition with other species for such
      sites appears to affect the intensity of intersexual selection in Coryphopterus
      nicholsi, a temperate goby that is a protogynous hermaphrodite. Field
      manipulations demonstrated that, within a population, the proportion of males
      that breed, and therefore the intensity of sexual selection, depends on the
      number of suitable nest rocks. The abundance of nest sites may also affect the
      timing of sex change in this species. Collections from areas with many suitable
      nest sites contained a higher proportion of males than collections from areas
      with few suitable nest sites. Aggression among males probably determines which
      individuals within the population can monopolize a suitable nest site and
      therefore are able to mate as a male. Field observations indicated that
      aggressive interactions occur frequently and that the larger individual of an
      interacting pair almost inevitably chases off the smaller individual during
      aggressive encounters. In field collections, males guarding eggs averaged larger
      in size than males not guarding eggs, and large males guarded nest sites that
      were superior to those guarded by small males. Competitors, including a large
      fish and several invertebrates, monopolize rocks otherwise suitable for
      Coryphopterus' use and thereby limit the number and proportion of breeding males
      in the goby's population. Field and laboratory observations and experiments
      indicated that a larger fish, Porichthys notatus, displaces Coryphopterus from
      nest sites and prevents Coryphopterus from using many of the large rocks on the
      reef. Other animals, including encrusting invertebrates and sea urchins, may also
      reduce the suitability and availability of rocks as nest sites. Such competition
      for nest sites reduces the opportunity of breeding by small males and increases
      the number of mates per large breeding male. Interspecific competition should,
      therefore, increase selection for protogynous hermaphroditism in Coryphopterus by
      increasing the reproductive advantage of large over small males. I discuss the
      possibility that interspecific competition may be an important selective force in
      resource-based mating systems of other animals and present potential examples
      from the literature.

PMID- 29357180
TI  - Predator Foraging Characteristics and Prey Population Structure on a Sheltered
      Shore.

PMID- 29357181
TI  - Demographic Consequences of Larval Development Mode: Planktotrophy vs.
      Lecithotrophy in Streblospio Benedicti.
AB  - This paper examines the demographic consequences of planktotrophic and
      lecithotrophic development in an estuarine polychaete. Two strains of Streblospio
      benedicti (Spionidae) were reared in the laboratory from birth through death at
      20 degrees C and salinity 34%. Survivorship and reproductive data were collected
      weekly and were used to construct life tables and population projection matrices
      for each development mode. Planktotrophic females reproduced earlier, and had
      higher fecundity and a shorter generation time than lecithotrophic females, but
      also exhibited higher mortality early in life. Despite the apparently
      opportunistic nature of the planktotrophic life history traits, the finite rate
      of increase (l) in the lecithotrophic strain (1.319 wk-1 ) exceeded that of the
      planktotrophic strain (1.205 wk-1 ). Net reproductive rate (R0 ) was also higher
      for the lecithotrophs (93.4) than for the planktotrophs (17.6) Peak reproductive
      values were attained earlier in planktotrophs than in lecithotrophs. Sensitivity
      analyses indicate that l is most sensitive to changes in larval and juvenile
      survivorship, and that the differences in l were almost completely determined by
      life table differences during the first 15 wk of life. The potential population
      growth rates obtained in this study agree well with those estimated for other
      opportunistic polychaete species such as Capitella sp. I and Polydora ligni.
      Under uniform conditions the two strains of S. benedicti achieved similar growth
      rates with very different life history traits. We hypothesize that each
      combination of traits may be adaptive under different circumstances in the field.

PMID- 29357182
TI  - Soil Acidity Affects Distribution, Behavior, and Physiology of the Salamader
      Plethodon Cinereus.
AB  - Censuses at two sites in Delaware County, New York from spring 1981 through
      spring 1985 indicated that the density and distribution of Plethodon cinereus
      were influenced by soil pH but not by soil temperature or moisture. Of 1044 1-m2
      quadrats of forest litter searched, 284 had a pH of 3.7 or less only 25 of these
      (8.8%) contained salamanders. Of 760 quadrats with a pH 3.8 or more, 386 (50.8%)
      contained salamanders. Juvenile salamanders were never found on soils with a pH
      @< 3.7. Seasonal salamander density was correlated (r = 0.92) with the percentage
      of quadrats with a pH of 3.7 and less. Salamanders apparently were excluded from
      27% of forest habitat because of low soil pH. In the laboratory, P. cinereus
      preferred to occupy substrates near neutral pH when given a choice among three
      levels of substrate acidity. The acutely lethal pH was between 2.5 and 3 and the
      8-mo chronically lethal pH was between 3 and 4. Growth and respiration were
      reduced at low pHs. The influence of soil pH on salamander distribution might
      fundamentally change the forest floor decomposer food web of which P. cinereus is
      an upper-level consumer.

PMID- 29357183
TI  - Demography of a Habitat Generalist, The White-Footed Mouse, in a Heterogeneous
      Environment.
AB  - A population of white-footed mice (Peromyscus leucopus) in southeastern
      Massachusetts was lived-trapped monthly in five habitat types for 5 yr in order
      to study the demography of a habitat generalist. We identified three demographic
      groups (two of low density and one of high density), which differed primarily in
      density, adult survival, proportion of males breeding, and variability in the
      proportion of males. The low-density segments of this population were at times
      able to achieve demographic performance equivalent to the high-density segments.
      Several demographic variables were related linearly to microhabitat gradients
      derived from a principal components analysis of 24 habitat variables, but similar
      demographic structure was found in different habitat types. A simple model is
      presented that relates demography to environmental suitability in a habitat
      generalist. According to this model, population density, productivity, and
      survival increase, and numerical and demographic variability decrease, along a
      gradient of increasing environmental suitability. Intensity of intrinsic
      regulation also may increase with environmental suitability, which would
      contribute to population stability. We hypothesize that in habitat generalists
      such as Peromyscus leucopus, population numbers are regulated along a stable
      trajectory in areas of high suitability, but may show little or no intrinsic
      regulation in poorer habitats. Furthermore, demographic structure may shift as
      environmental conditions improve or decline in quality. This highly flexible
      demographic structure may enable populations of generalists to persist in poor
      habitats.

PMID- 29357184
TI  - Tree Lizard (Urosaurus Ornatus) Territories: Experimental Perturbation of the Sex
      Ratio.

PMID- 29357185
TI  - The Influences of Conspecific and Heterospecific Residents on Colonization.
AB  - To determine if dispersing prairie voles, Microtus ochrogaster, are prevented
      from establishing home ranges in habitat already occupied by conspecifics or
      potentially competitive species, voles were introduced into enclosed populations
      of: the same species; southern bog lemmings, Synaptomys cooperi; cotton rats,
      Sigmodon hispidus; or an empty enclosure. The results indicated that colonization
      by dispersing voles was negatively affected by resident conspecifics. Introduced
      females were more strongly affected than males during the vegetative growing
      season but not during the nongrowing season when reproductive activity is
      typically low. Resident bog lemmings also negatively affected colonization by
      dispersing voles. However, both sexes of introduced voles were similarly affected
      in both seasons. There was no evidence of postcolonization competitive effects,
      suggesting that interspecific competition does not occur between established
      resident individuals. Cotton rats, which have only recently become part of the
      small mammal community in Kansas, did not adversely affect colonization by
      dispersing voles or have adverse post-colonization effects on their survival and
      reproduction. The ability of residents to inhibit colonization by another species
      may facilitate the coexistence of M. ochrogaster and Synaptomys cooperi by
      retarding the competitive exclusion of either species until annual fluctuations
      in reproduction and density create an abundance of suitable but unoccupied space.
      This type of coexistence is similar to the storage effect in lottery models of
      competitive coexistence.

PMID- 29357186
TI  - Role of Tannins in Defending Plants Against Ruminants: Reduction in Dry Matter
      Digestion?
AB  - Polyphenolic allelochemicals, such as tannins, are widely thought to reduce the
      digestibility of plants consumed by herbivores by binding to digestive enzymes
      and dietary proteins. While the apparent digestibility of protein and, therefore,
      cell solubles is reduced in mule deer (Odocoileus hemionus) and white-tailed deer
      (O. virginianus) consuming tanniferous forages, digestion of the plant cell wall
      is not reduced beyond that predicted from its content of lignin, cutin, and
      silica. The lack of a tannin effect on cell wall digestion in deer is in contrast
      to studies with domestic sheep and numerous in vitro studies. Herbivores adapted
      to consume tanniferous forages may defend against such allelochemicals by
      producing salivary proteins that bind tannins in a highly specific manner. These
      tannin-salivary protein complexes would reduce apparent digestibilities of
      protein and cell solubles and, if completely effective, would not reduce cell
      wall digestion. The occurrence of such proteins in ruminants is reported here for
      the first time. The saliva composition of mule deer (a mixed feeder that commonly
      consumes browse) and domestic cattle and sheep (predominant grazers) are
      compared, and the higher potential of the deer saliva to neutralize tannins is
      related to their feeding habits. Salivary proteins that preferentially bind
      tannins may minimize fecal nitrogen losses by maximizing the efficiency of tannin
      binding per unit of protein and may reduce the absorption of hydrolyzable tannins
      and the potential for tannin toxicity.

PMID- 29357187
TI  - Patch Size, Pollinator Behavior, and Pollinator Limitation in Catnip.
AB  - We examined the effects of the patch size of catnip, Nepeta cataria, on
      pollinator visitation rates and pollinator limitation. The most important floral
      visitors were honey bees (Apis mellifera), solitary bees (Halictidae), and bumble
      bees (Bombus spp.). Our first goal was to see how spatial variation in patch size
      affected the rate at which individual flowers received pollinator visits
      (visitation rate). Visitation rate was higher in larger patches for honey bees
      and bumble bees, but lower for solitary bees. Patch size explained 74-83% of the
      variation in visitation rate. Intraspecific isolation also had an effect:
      isolated patches received relatively few visits. Visitation rate depended both on
      visitor abundance and on the proportion of flowers entered during one visit. All
      three visitor types wee more abundant in larger patches, i.e., flowers showed
      mutual attraction of pollinators. Relative to a visit to a small patch, during a
      visit to a large patch, honey bees visited more flowers but a lower proportion of
      flowers; solitary bees visited fewer flowers and thus a lower proportion of
      flowers; and bumble bees visited not only more flowers but a higher proportion of
      flowers as well. Thus within patches, flowers competed for visits from honey bees
      and solitary bees but showed facilitation regarding bumble bee visits. Our second
      goal was to relate patch size and visitation rates to immediate pollinator
      limitation. Comparisons of the percent of capsules setting seed (fruit set) of
      open-pollinated, hand-pollinated, and bagged flowers were used to evaluate
      pollinator limitation. The ranking of fruit set was: hand-pollinated > open
      pollinated > bagged. Patch size did not affect fruit set in hand-pollinated or
      bagged flowers; however, for open-pollinated flowers, fruit set was lower in
      smaller patches. patch size explained 63% of the variation in pollinator
      limitation. The effect of patch size comes through its effects on visitation
      rates. A multiple regression model using visitation rates of the three types of
      visitors as independent variables explained 67% of the variation in pollinator
      limitation.

PMID- 29357188
TI  - Can one simple questionnaire assess substance-related and behavioural addiction
      problems? Results of a proposed new screener for community epidemiology.
AB  - BACKGROUND AND AIMS: There is currently no well-validated measure that assesses a
      broad spectrum of substance-related and behavioural addictions in general
      populations. This study aimed to develop a brief self-attribution Screener for
      Substance and Behavioural Addictions (SSBA) to screen for four substances and six
      behaviours, and to compare its performance with established individual-behaviour
      screening instruments. DESIGN: A small, psychometrically optimal set of items to
      assess self-attributed indicators of addiction across alcohol, tobacco, cannabis,
      cocaine, gambling, shopping, videogaming, overeating, sexual activity and
      overworking were identified from a broader pool that was developed using a lay
      epidemiology qualitative approach. The suitability of the four-item single-factor
      solution was tested for each behaviour and scores were compared with those
      obtained from the sample using individual-behaviour screening instruments.
      SETTING AND PARTICIPANTS: Participants (n = 6000), broadly representative of the
      Canadian English-speaking adult population, were recruited through the Ipsos Reid
      Canadian Online Panel. MEASUREMENTS: Participants completed an item pool of 15
      indicators of addiction for each target behaviour and a validation instrument for
      one randomly assigned behaviour. FINDINGS: A set of four items identified using
      principal component and confirmatory factor analyses demonstrated good fit and
      excellent internal consistency (alpha = 0.87-0.95) across behaviours, and good
      convergent validity (rs = 0.44-0.8) with extant instruments measuring similar
      constructs, with only one exception (r = 0.26). CONCLUSIONS: The proposed
      Screener for Substance and Behavioural Addiction is a reliable and valid measure
      assessing the lay public's self-attributed indicators of addiction across 10
      substances and behaviours.

PMID- 29357189
TI  - Change Pathways in Indigenous and Nonindigenous Youth Suicide.
AB  - Multivariate dynamic relationships among suicide attempts, anxiety and/or
      depressive symptoms, hope, and help-seeking were examined across time in Native
      Hawaiian and non-Hawaiian adolescents, using data from a 5-year longitudinal
      cohort study (N = 7,317). The rate of suicide attempts decreased over time, but
      this reduction was significantly less among Native Hawaiian youth than their non
      Hawaiian peers. There were also significant differences between groups in hope
      and help-seeking, with Native Hawaiian youth increasing help-seeking and
      decreasing hope to a greater degree. Youth-centered, cultural approaches to
      suicide prevention are essential in enhancing well-being in indigenous
      communities.

PMID- 29357191
TI  - Reply.

PMID- 29357193
TI  - Searching cerebrovascular risk indicators for hypertensive patients: Is
      Framingham Stroke Risk Profile "the magic bullet"?

PMID- 29357190
TI  - Candidate biomarkers for the diagnosis and prognosis of drug-induced liver
      injury: An international collaborative effort.
AB  - : Current blood biomarkers are suboptimal in detecting drug-induced liver injury
      (DILI) and predicting its outcome. We sought to characterize the natural
      variabilty and performance characteristics of 14 promising DILI biomarker
      candidates. Serum or plasma from multiple cohorts of healthy volunteers (n = 192
      and n = 81), subjects who safely took potentially hepatotoxic drugs without
      adverse effects (n = 55 and n = 92) and DILI patients (n = 98, n = 28, and n =
      143) were assayed for microRNA-122 (miR-122), glutamate dehydrogenase (GLDH),
      total cytokeratin 18 (K18), caspase cleaved K18, glutathione S-transferase alpha,
      alpha-fetoprotein, arginase-1, osteopontin (OPN), sorbitol dehydrogenase, fatty
      acid binding protein, cadherin-5, macrophage colony-stimulating factor receptor
      (MCSFR), paraoxonase 1 (normalized to prothrombin protein), and leukocyte cell
      derived chemotaxin-2. Most candidate biomarkers were significantly altered in
      DILI cases compared with healthy volunteers. GLDH correlated more closely with
      gold standard alanine aminotransferase than miR-122, and there was a surprisingly
      wide inter- and intra-individual variability of miR-122 levels among healthy
      volunteers. Serum K18, OPN, and MCSFR levels were most strongly associated with
      liver-related death or transplantation within 6 months of DILI onset. Prediction
      of prognosis among DILI patients using the Model for End-Stage Liver Disease was
      improved by incorporation of K18 and MCSFR levels. CONCLUSION: GLDH appears to be
      more useful than miR-122 in identifying DILI patients, and K18, OPN, and MCSFR
      are promising candidates for prediction of prognosis during an acute DILI event.
      Serial assessment of these biomarkers in large prospective studies will help
      further delineate their role in DILI diagnosis and management. (Hepatology 2018).

PMID- 29357192
TI  - Negative regulation of type I IFN signaling.
AB  - Type I IFNs (alpha, beta, and others) are a family of cytokines that are produced
      in physiological conditions as well as in response to the activation of pattern
      recognition receptors. They are critically important in controlling the host
      innate and adaptive immune response to viral and some bacterial infections,
      cancer, and other inflammatory stimuli. However, dysregulation of type I IFN
      production or response can contribute to immune pathologies termed
      "interferonopathies", pointing to the importance of balanced activating signals
      with tightly regulated mechanisms of tuning this signaling. Here, we summarize
      the recent advances of how type I IFN production and response are controlled at
      multiple levels of the type I IFN signaling cascade.

PMID- 29357194
TI  - Open-label study of cognitive behavioural therapy for individuals with at-risk
      mental state: Feasibility in the Japanese clinical setting.
AB  - AIM: To date, most cognitive behavioural therapy (CBT) trials for individuals
      with at-risk metal state (ARMS) have been conducted in few Western countries and
      its feasibility in other regions, including Japan, has not been established.
      METHODS: We designed an open-label pilot study. Fourteen ARMS participants
      received CBT over 6 months and were followed-up for 6 months. RESULTS: Thirteen
      individuals completed the CBT intervention and assessments. The mean total score
      on the Positive and Negative Syndrome Scale improved from 60.2 to 46.0 after the
      intervention (Cohen's d = 1.1). The effects were maintained at the follow-up
      assessment. One participant transitioned to psychosis after the CBT intervention,
      and was the only patient who received antipsychotics. CONCLUSIONS: We confirmed
      the feasibility of the provision of CBT for ARMS in Japan. Since overprescription
      of antipsychotics is a matter of great concern in Japan, CBT could be a valuable
      alternative treatment strategy.

PMID- 29357195
TI  - Creatine kinase, sodium retention, and blood pressure: Is there a link?

PMID- 29357196
TI  - Bilateral branch pulmonary artery valve implantation in repaired tetralogy of
      fallot.
AB  - BACKGROUND: Transcatheter, bilateral branch pulmonary artery (PA) valve
      implantation is a novel treatment for patients with severe pulmonary
      insufficiency and oversized right ventricle (RV) outflow tract. There is scarce
      data on efficacy and safety of this approach. METHODS: This was a retrospective
      study of 8 patients with repaired tetralogy of fallot (TOF) who underwent
      bilateral branch PA valve implantation. Demographics, echocardiography, cardiac
      catheterization, and axial imaging data were reviewed. Variables were compared by
      a paired sample t-test. RESULTS: All patients were adult sized (weight 43-99 kg)
      with oversized RV outflow tract not suitable for conventional transcatheter
      pulmonary valve implantation. Staged bare metal PA stenting followed by valve
      implantation (interval 3-5 months) was technically successful in 7 patients with
      one stent embolization. In another patient, proximal stent migration prevented
      placement of bilateral pulmonary valve stents. There were a total of 14 valved
      branch PA stents placed (Melody valve n = 9, Sapien XT n = 2, Sapien 3 n = 3). In
      the 7 patients undergoing successful branch pulmonary valve placement, at median
      follow up of 10 months (range 3 months to 6 years), 13 (93%) valves had
      none/trivial insufficiency on echocardiography. Prevalve and postvalve
      implantation cardiac magnetic resonance imaging in five patients showed
      significant reduction of indexed RV end-diastolic volume (152 +/- 27 to 105 +/-
      15 mL/m2 , P < .001). CONCLUSIONS: Transcatheter, bilateral branch PA valve
      implantation was technically feasible with satisfactory efficacy and safety in
      patients with repaired TOF, severe pulmonary insufficiency, and oversized RV
      outflow tracts. Elimination of pulmonary insufficiency with this method resulted
      in reduced RV end-diastolic volume. This approach can be offered as an
      alternative to surgery, particularly in patients considered high risk for
      standard surgical placement and who are not candidates for the newer self
      expanding valve prosthesis for placement in RV outflow tracts larger than 30 mm
      diameter.

PMID- 29357197
TI  - The Pepi-Pod study: Overnight video, oximetry and thermal environment while using
      an in-bed sleep device for sudden unexpected death in infancy prevention.
AB  - AIM: The aim of this study was to identify the potential risks and benefits of
      sleeping infants in a Pepi-Pod distributed to families with high risk of sudden
      unexpected death in infancy compared to a bassinet. METHODS: Forty-five mostly
      indigenous Maori mothers who were referred by local health providers to receive a
      Pepi-Pod were surveyed at recruitment, 1 and 3 months. A sleep study at 1 month
      included infrared video, oximetry and temperature measures. RESULTS: When
      compared with 89 historical bassinet controls, an intention-to-treat analysis of
      questionnaires showed no increase in direct bed sharing but demonstrated
      significantly less sharing of the maternal bedroom at both interviews, with the
      majority of those not sleeping in the maternal bedroom, actually sleeping in the
      living room. The 1 month 'as-used' analysis showed poorer maternal sleep quality.
      The 'as-used' analysis of video data (24 Pepi-Pod and 113 bassinet infants) also
      showed no increase in direct bed sharing, head covering or prone/side sleep
      position. Differences in oxygen saturation were not significant, but heart rate
      was higher in the Pepi-Pod infants by 8.37 bpm (95% confidence interval 4.40,
      12.14). Time in the thermal comfort zone was not different between groups despite
      Pepi-Pod infants being situated in significantly warmer rooms. CONCLUSIONS:
      Overall, we found that most differences in infant risk behaviours in a Pepi-Pod
      compared to a bassinet were small, with confidence intervals excluding meaningful
      differences. We noted poorer maternal sleep quality at 1 month. Higher infant
      heart rates in the Pepi-Pod group may be related to higher room temperatures. The
      Pepi-Pod appears physiologically safe but is associated with lower reported
      maternal sleep quality.

PMID- 29357199
TI  - Creatine kinase and renal sodium excretion in African and European men on a high
      sodium diet.
AB  - Creatine kinase (CK) rapidly regenerates ATP for Na+ /K+ -ATPase driven sodium
      retention throughout the kidney. Therefore, we assessed whether resting plasma CK
      is associated with sodium retention after a high sodium diet. Sixty healthy men
      (29 European and 31 African ancestry) with a mean age of 37.2 years (SE 1.2) were
      assigned to low sodium intake (< 50 mmol/d) during 7 days, followed by 3 days of
      high sodium intake (> 200 mmol/d). Sodium excretion (mmol/24-h) after high sodium
      was 260.4 (28.3) in the high CK tertile versus 415.2 (26.3) mmol/24-h in the low
      CK tertile (P < .001), with a decrease in urinary sodium excretion of 98.4
      mmol/24-h for each increase in log CK, adjusted for age and African ancestry.
      These preliminary results are in line with the energy buffering function of the
      CK system, but more direct assessments of kidney CK will be needed to further
      establish whether this enzyme enhances sodium sensitivity.

PMID- 29357198
TI  - Inactivation of nucleus reuniens impairs spatial working memory and behavioral
      flexibility in the rat.
AB  - The hippocampal formation (HF) and medial prefrontal cortex (mPFC) play critical
      roles in spatial working memory (SWM). The nucleus reuniens (RE) of the ventral
      midline thalamus is an important anatomical link between the HF and mPFC, and as
      such is crucially involved in SWM functions that recruit both structures. Little
      is known, however, regarding the role of RE in other behaviors mediated by this
      circuit. In the present study, we examined the role of RE in spatial working
      memory and executive functioning following reversible inactivation of RE with
      either muscimol or procaine. Rats were implanted with an indwelling cannula
      targeting RE and trained in a delayed nonmatch to sample spatial alternation T
      maze task. For the task, sample and choice runs were separated by moderate or
      long delays (30, 60, and 120 s). Following asymptotic performance, rats were
      tested following infusions of drug or vehicle. Muscimol infused into RE impaired
      SWM at all delays, whereby procaine only impaired performance at the longest
      delays. Furthermore, RE inactivation with muscimol produced a failure in win
      shift strategy as well as severe spatial perseveration, whereby rats persistently
      made re-entries into incorrect arms during correction trials, despite the absence
      of reward. This demonstrated marked changes in behavioral flexibility and
      response strategy. These results strengthen the role of nucleus reuniens as a
      pivotal link between hippocampus and prefrontal cortex in cognitive and executive
      functions and suggest that nucleus reuniens may be a potential target in the
      treatment of CNS disorders such as schizophrenia, attention deficit hyperactivity
      disorder, addiction, and obsessive-compulsive disorder, whose symptoms are
      defined by hippocampal-prefrontal dysfunctions.

PMID- 29357200
TI  - Improved detection of fMRI activation in the cerebellum at 7T with dielectric
      pads extending the imaging region of a commercial head coil.
AB  - BACKGROUND: There is growing interest in detecting cerebro-cerebellar circuits,
      which requires adequate blood oxygenation level dependent contrast and signal-to
      noise ratio (SNR) throughout the brain. Although 7T scanners offer increased SNR,
      coverage of commercial head coils is currently limited to the cerebrum. PURPOSE:
      To improve cerebellar functional MRI (fMRI) at 7T with high permittivity material
      (HPM) pads extending the sensitivity of a commercial coil. STUDY TYPE:
      Simulations were used to determine HPM pad configuration and assess
      radiofrequency (RF) safety. In vivo experiments were performed to evaluate RF
      field distributions and SNR and assess improvements of cerebellar fMRI. SUBJECTS:
      Eight healthy volunteers enrolled in a prospective motor fMRI study with and
      without HPM. FIELD STRENGTH/SEQUENCE: Gradient echo (GRE) echo planar imaging for
      fMRI, turbo FLASH for flip angle mapping, GRE sequence for SNR maps, and T1 
      weighted MPRAGE were acquired with and without HPM pads at 7T. ASSESSMENT: Field
      maps, SNR maps, and anatomical images were evaluated for coverage. Simulation
      results were used to assess SAR levels of the experiment. Activation data from
      fMRI experiments were compared with and without HPM pads. STATISTICAL TESTS: fMRI
      data were analyzed using FEAT FSL for each subject followed by group level
      analysis using paired t-test of acquisitions with and without HPM. RESULTS:
      Simulations showed 52% improvement in transmit efficiency in cerebellum with HPM
      and SAR levels well below recommended limits. Experiments showed 27% improvement
      in SNR in cerebellum and improvement in coverage on T1 -weighted images. fMRI
      showed greater cerebellar activation in individual subjects with the HPM pad
      present (Z > = 4), especially in inferior slices of cerebellum, with 59% average
      increase in number of activated voxels in the cerebellum. Group-level analysis
      showed improved functional activation (Z > = 2.3) in cerebellar regions with HPM
      pads without loss of measured activation elsewhere. DATA CONCLUSION: HPM pads can
      improve cerebellar fMRI at 7T with a commonly-used head coil without compromising
      RF safety. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON.
      IMAGING 2018;48:431-440.

PMID- 29357201
TI  - Hidden estrogen production from ovarian remnants leading to progression of
      disease in metastatic breast cancer.
AB  - In premenopausal women with hormone dependent breast cancers, ovarian suppression
      is an important part of treatment, and is often achieved with a bilateral
      salpingo-oophorectomy (BSO). However, this procedure can lead to ovarian remnant
      syndrome (ORS), a rare condition where the adnexal tissue is not completely
      removed and can produce estrogen. We describe a case of ORS in a patient with
      estrogen receptor positive (ER+) breast cancer who had progression of disease
      after undergoing a BSO, despite optimal therapy. ORS therefore poses a
      significant treatment challenge in premenopausal ER+ breast cancer patients
      thought to be rendered menopausal with a BSO.

PMID- 29357202
TI  - Framingham Stroke Risk Profile is related to cerebral small vessel disease
      progression and lower cognitive performance in patients with hypertension.
AB  - The Framingham Stroke Risk Profile (FSRP) was developed to predict clinical
      stroke. We investigated if FSRP is associated with more "silent" effects of
      cerebrovascular disease, namely progression of cerebral small vessel disease
      (cSVD)-related brain damage and cognitive performance in hypertensive patients.
      Ninety patients with essential hypertension underwent a brain MRI scan and FSRP
      assessment at baseline, and a second brain MRI scan and neuropsychological
      assessment at 9-year follow-up. We visually rated progression of cSVD-related MRI
      markers. FSRP was associated with progressive periventricular white matter
      hyperintensities (P = .017) and new microbleeds (P = .031), but not after
      correction for the FSRP age component. FSRP was associated with lower overall
      cognitive performance (P < .001) and this remained significant after correction
      for the FSRP age component. A vascular risk score might be useful in predicting
      progression of cSVD-related brain damage or future cognitive performance in
      hypertensive patients. Age seems to be the most important component in FSRP.

PMID- 29357204
TI  - Clinical Medicine From 10,000 Feet.

PMID- 29357203
TI  - BAUS consensus document for the management of male genital emergencies: priapism.
AB  - Male genital emergencies relating to the penis and scrotum are rare and require
      prompt investigation and surgical intervention. Clinicians are often unfamiliar
      with the management of these conditions and may not work in a specialist centre
      with on-site expertise in genitourethral surgery. A series of consensus
      statements have been developed by an expert consensus committee comprising
      members of the BAUS Section of Andrology and Genitourethral Surgery together with
      experts from urology units throughout the UK. Priapism requires prompt assessment
      and treatment and these consensus statements provide guidance for UK practice.

PMID- 29357205
TI  - My Mentor.

PMID- 29357206
TI  - Beyond the Clinic: Making a Difference in the Lives of Others.

PMID- 29357207
TI  - Differences in Methods of Self-Inflicted Injuries by Sex in Wisconsin, 2002-2014.
AB  - BACKGROUND: Despite suicide prevention efforts, there remains a high burden of
      self-inflicted injuries in Wisconsin. OBJECTIVE: Compare methods of suicide and
      nonfatal self-inflicted injury by sex in Wisconsin over a 12-year period.
      METHODS: Suicide and nonfatal self-inflicted injury rates in Wisconsin between
      2002 and 2014 were compared by sex and method using data from the Wisconsin
      Interactive Statistics on Health. Percentages of total suicides by method of
      injury for each sex were calculated. RESULTS: Firearms and poisoning were the
      most common methods of suicide and nonfatal selfinflicted injuries, respectively.
      Rates of both suicide and nonfatal self-inflicted injuries differed significantly
      by sex and method. CONCLUSIONS: Suicide prevention strategies in Wisconsin must
      account for the variability of method of self-inflicted injury between sexes.

PMID- 29357208
TI  - Muscle Cramps Do Not Improve With Correction of Vitamin D Insufficiency.
AB  - BACKGROUND: Minimal treatment options exist for idiopathic muscle cramps.
      OBJECTIVE: We evaluated whether correction of vitamin D insufficiency relieved
      muscle cramps in postmenopausal women. METHODS: We conducted a post hoc analysis
      of a randomized, double-blind, placebo-controlled trial at a single academic
      medical center in the Midwest to evaluate the benefits of treating vitamin D
      insufficiency. Two hundred thirty postmenopausal women participated. Eligible
      women were <=75 years old, 5 years past menopause or oophorectomy, or >=60 years
      if they had previously undergone hysterectomy without oophorectomy. Women had
      vitamin D insufficiency at baseline (25-hydroxyvitamin D 14-27 ng/mL). We
      excluded subjects with a glomerular filtration rate <45 mL/minute. INTERVENTIONS
      FOR CLINICAL TRIALS: Participants completed food diaries, laboratory studies, and
      functional tests including the Timed Up and Go test, Physical Activity Scale for
      the Elderly, Health Assessment Questionnaire (a measure of disability), and pain
      scores. Subjects recorded muscle cramp frequency and severity using a
      standardized form at 6 visits over 1 year. RESULTS: During the trial, over half
      of participants (n=121, 53%) reported muscle cramps. Despite unequivocal vitamin
      D repletion, vitamin D had no effect on muscle cramps. Pain levels, disability,
      and dietary potassium predicted presence of cramps. Serum albumin and physical
      activity were inversely associated with, and disability was positively associated
      with, severity of muscle cramps. CONCLUSIONS: Further studies are needed to
      evaluate the link between pain, disability, dietary potassium intake, and muscle
      cramps.

PMID- 29357209
TI  - Travel During Pregnancy: Results From an Ultrasound Unit-Based Questionnaire.
AB  - BACKGROUND: The frequency of domestic and international travel among women
      residing in the United States, and specifically Wisconsin, during pregnancy is
      not known. Given the recent epidemic of Zika virus disease, clinicians should be
      aware of the frequency of travel during pregnancy and should inquire about travel
      by pregnant women, women of reproductive age, and their sexual partners. METHODS:
      Due to the Zika epidemic, our obstetric ultrasound center added questions about
      international and domestic travel to a general health form that is routinely
      distributed to all patients presenting for anatomic ultrasounds. The forms were
      then collected and recorded in order to provide an estimate of the frequency of
      travel during the first half of pregnancy. RESULTS: Of 1,256 women screened, 64
      (5.1%) traveled internationally and 498 (39.6%) traveled domestically prior to
      their anatomic ultrasound. Additionally, 77 (6.1%) women screened reported
      international travel by their sexual partner. Among international travelers, 20
      (28.1%) traveled to destinations with active ongoing transmission of Zika virus
      disease, and 16 (25%) traveled after the Centers for Disease Control and
      Prevention (CDC) issued a travel alert for the area. Among domestic travelers,
      Florida was the sixth most common destination, and Texas was the 10th most
      common. CONCLUSIONS: In the population of women screened by this questionnaire,
      5.1% traveled internationally and 39.6% traveled domestically prior to their
      anatomic ultrasound. Notably, Florida and Texas are common travel destinations
      among women at this clinic, and both have had active local transmission of Zika
      virus.

PMID- 29357211
TI  - Severe Maternal Morbidity During Delivery Hospitalizations.
AB  - INTRODUCTION: Severe maternal morbidities include 25 complications resulting
      from, or exacerbated by, pregnancy. Nationally, in the last decade, these rates
      have doubled. OBJECTIVE: This study describes trends in the rates of severe
      maternal morbidities at the time of hospitalization for delivery among different
      groups of Wisconsin women. METHODS: Hospital discharge data and ICD-9-CM
      diagnosis and procedure codes were used to identify delivery hospitalizations and
      rates of severe maternal morbidity among Wisconsin women from 2000 to 2014.
      Subsequent analyses focused on recent years (2010-2014). Rates of severe maternal
      morbidity were calculated per 10,000 delivery hospitalizations for all 25 severe
      maternal morbidity conditions as well as 24 conditions (excluding blood
      transfusions). Rates and rate ratios were calculated overall and for
      racial/ethnic groups, age groups, public health region of residence, and hospital
      payer. Median hospital length of stay and median hospital charges were compared
      for delivery hospitalizations with increasing severe maternal morbidities.
      RESULTS: Severe maternal morbidity rates increased 104% from 2000 to 2014 (P for
      trend <0.01). After excluding blood transfusions, rates increased 15% (P for
      trend <0.05). From 2010 to 2014, overall rates were stable over time, but varied
      by maternal age, race/ethnicity, payer, and public health region of residence.
      Median hospital charges and length of stay increased as the number of morbidities
      increased. CONCLUSIONS: Monitoring severe maternal morbidities adds valuable
      information to understanding perinatal health and obstetric complications in
      order to identify opportunities for prevention of severe morbidities and
      improvements in the quality of maternity care.

PMID- 29357210
TI  - Risk Factors Associated With Carbapenem-Resistant Pseudomonas aeruginosa.
AB  - INTRODUCTION: Pseudomonas aeruginosa infections resistant to carbapenem
      antimicrobials have increased. Traditional risk factors for non-carbapenem
      resistance include intensive care unit stay, mechanical ventilation, previous
      hospitalization, and major comorbidities. As microbes evolve, our understanding
      of their risk factors for resistance also should evolve. METHODS: We conducted a
      retrospective study of adult inpatients and outpatients with a positive
      Pseudomonas aeruginosa culture during 2014. Cultures were obtained from system
      laboratories and medical records were reviewed through our electronic medical
      record. Pearson's chi-squared test with Yates correction and 2-sample t-tests
      were performed on categorical and continuous variables, respectively. Binary
      regression was used for multivariable modeling. RESULTS: Patients (N=1,763), of
      mean age 68.0 years and body mass index (BMI) 30.4 kg/m2, were more likely to be
      women (51.3%) and were predominately white (89.3%). Resistance to imipenem or
      meropenem (14.0%) on univariable analysis was associated with several variables
      of interest. Non-white race (odds ratio [OR] =1.67; P=0.009), respiratory
      cultures (OR=1.95; P=0.003), recent institutional transfer (OR=2.50; P<0.0001),
      vasopressor use (OR=1.98; P=0.001), central line placement (OR=1.55; P=0.036),
      and peripherally inserted central catheter placement (OR=1.74; P=0.002) remained
      significant predictors of carbapenem resistance in multivariable modeling.
      CONCLUSION: Demographic and traditional risk factors, as well as respiratory
      cultures, were predictive of carbapenem resistance and may guide initial
      antibiotic treatment. Use of "last resort" antibiotics for Pseudomonas aeruginosa
      based solely on patient chronic conditions may not be necessary. Fortunately, <1%
      of strains were resistant to all drugs tested. Ongoing efforts to face drug
      resistant organisms are warranted.

PMID- 29357212
TI  - Case Report of Metronidazole-Induced Encephalopathy.
AB  - This report describes the case of an 83-year-old woman who was admitted to a
      hospitalist service with weakness and falls. She was transferred from an outside
      facility where she was treated with 3 courses of metronidazole for diagnosed
      Clostridium difficile colitis and presumed reoccurrences. Magnetic resonance
      imaging (MRI) demonstrated T2 enhancement of the dorsal pons and dentate nuclei
      consistent with metronidazole-induced encephalopathy. Her metronidazole was
      stopped and her symptoms resolved. This condition is rare, poorly understood, and
      causes reversible changes in the brain that are detectable through T2-weighted
      MRI. It will need ongoing study with current widespread use of metronidazole.

PMID- 29357213
TI  - Women's Health Care in Wisconsin: A Closer Look.

PMID- 29357214
TI  - Skin and Diet: An Update on the Role of Dietary Change as a Treatment Strategy
      for Skin Disease.
AB  - An increasing body of research indicates that dietary change may serve as a
      component of therapy for certain skin conditions. This includes conditions such
      as acne, atopic dermatitis, aging skin, psoriasis, and rosacea. Certain
      nutrients, foods, or dietary patterns may act as disease "triggers", while others
      may prove beneficial. Avoidance or elimination diets may be helpful in some
      conditions, although testing may be recommended first. In terms of beneficial
      effects, an eating pattern that emphasizes the consumption of whole foods over
      highly processed foods may help in the treatment of certain skin conditions, and
      will certainly help in the prevention of associated co-morbidities.

PMID- 29357215
TI  - New Treatments for Hereditary Angioedema.
AB  - Hereditary angioedema is characterized by severe, episodic edema of the
      subcutaneous and mucosal tissue. The disease carries significant morbidity and
      mortality due to involvement of the gastrointestinal tract and upper airway.
      Recent advances in the treatment of hereditary angioedema include new techniques
      used to isolate and purify human-derived C1 inhibitor, the production of a
      recombinant form of C1 inhibitor, and the development of drugs that target the
      kallikrein-kinin pathway. This paper reviews the mechanisms, efficacy, and
      adverse reactions associated with these medications.

PMID- 29357216
TI  - Purity Determination by Capillary Electrophoresis Sodium Hexadecyl Sulfate (CE
      SHS): A Novel Application For Therapeutic Protein Characterization.
AB  - Capillary gel electrophoresis using sodium dodecyl sulfate (CE-SDS) is used
      commercially to provide quantitative purity data for therapeutic protein
      characterization and release. In CE-SDS, proteins are denatured under reducing or
      nonreducing conditions in the presence of SDS and electrophoretically separated
      by molecular weight and hydrodynamic radius through a sieving polymer matrix.
      Acceptable performance of this method would yield protein peaks that are baseline
      resolved and symmetrical. Nominal CE-SDS conditions and parameters are not
      optimal for all therapeutic proteins, specifically for Recombinant Therapeutic
      Protein-1 (RTP-1), where acceptable resolution and peak symmetry were not
      achieved. The application of longer alkyl chain detergents in the running buffer
      matrix substantially improved assay performance. Matrix running buffer containing
      sodium hexadecyl sulfate (SHS) increased peak resolution and plate count 3- and 8
      fold, respectively, compared to a traditional SDS-based running gel matrix. At
      Bristol-Myers Squibb (BMS), we developed and qualified a viable method for the
      characterization and release of RTP-1 using an SHS-containing running buffer
      matrix. This work underscores the potential of detergents other than SDS to
      enhance the resolution and separation power of CE-based separation methods.

PMID- 29357217
TI  - Localized DNA Hybridization Chain Reactions on DNA Origami.
AB  - The field of DNA nanoscience has demonstrated many exquisite DNA nanostructures
      and intricate DNA nanodevices. However, the operation of each step of prior
      demonstrated DNA nanodevices requires the diffusion of DNA strands, and the speed
      of these devices is limited by diffusion kinetics. Here we demonstrate chains of
      localized DNA hybridization reactions on the surface of a self-assembled DNA
      origami rectangle. The localization design for our DNA nanodevices does not rely
      on the diffusion of DNA strands for each step, thus providing faster reaction
      kinetics. The locality also provides considerable increased scalability, since
      localized components of the devices can be reused in other locations. A variety
      of techniques, including atomic force microscopy, total internal reflection
      fluorescence, and ensemble fluorescence spectroscopy, are used to confirm the
      occurrence of localized DNA hybridization reactions on the surface of DNA
      origami. There are many potential biological applications for our localized DNA
      nanodevices, and the localization design is extensible to applications involving
      DNA nanodevices operating on other molecular surfaces, such as those of the cell.

PMID- 29357218
TI  - Dual-Functional Graphene Carbon as Polysulfide Trapper for High-Performance
      Lithium Sulfur Batteries.
AB  - The lithium sulfur (Li-S) battery has attracted much attention due to its high
      theoretical capacity and energy density. However, its cycling stability and rate
      performance urgently need to improve because of its shuttle effect. Herein,
      oxygen-doped carbon on the surface of reduced graphene oxide (labeled as ODC/rGO)
      was fabricated to modify the separators of Li-S batteries to limit the
      dissolution of the lithium polysulfides. The mesoporous structure in ODC/rGO can
      not only serve as the physical trapper, but also provide abundant channels for
      fast ion transfer, which is beneficial for effective confinement of the
      dissoluble intermediates and superior rate performance. Moreover, the oxygen
      containing groups in ODC/rGO are able to act as chemical adsorption sites to
      immobilize the lithium polysulfides, suppressing their dissolution in electrolyte
      to enhance the utilization of sulfur cathode in Li-S batteries. As a result,
      because of the synergetic effects of physical adsorption and chemical interaction
      to immobilize the soluble polysulfides, the Li-S batteries with the ODC/rGO
      coated separator exhibit excellent rate performance and good long-term cycling
      stability with 0.057% capacity decay per cycle at 1.0 C after 600 cycles.

PMID- 29357219
TI  - Nasicon-Type Surface Functional Modification in Core-Shell
      LiNi0.5Mn0.3Co0.2O2@NaTi2(PO4)3 Cathode Enhances Its High-Voltage Cycling
      Stability and Rate Capacity toward Li-Ion Batteries.
AB  - Surface modifications are established well as efficient methodologies to enhance
      comprehensive Li-storage behaviors of the cathodes and play a significant role in
      cutting edge innovations toward lithium-ion batteries (LIBs). Herein, we first
      logically devised a pilot-scale coating strategy to integrate solid-state
      electrolyte NaTi2(PO4)3 (NTP) and layered LiNi0.5Mn0.3Co0.2O2 (NMC) for smart
      construction of core-shell NMC@NTP cathodes. The Nasicon-type NTP nanoshell with
      exceptional ion conductivity effectively suppressed gradual encroachment and/or
      loss of electroactive NMC, guaranteed stable phase interfaces, and meanwhile
      rendered small sur-/interfacial electron/ion-diffusion resistance. By benefiting
      from immanently promoting contributions of the nano-NTP coating, the as
      fabricated core-shell NMC@NTP architectures were competitively endowed with
      superior high-voltage cyclic stabilities and rate capacities within larger
      electrochemical window from 3.0 to 4.6 V when utilized as advanced cathodes for
      advanced LIBs. More meaningfully, the appealing electrode design concept proposed
      here will exert significant impact upon further constructing other high-voltage
      Ni-based cathodes for high-energy/power LIBs.

PMID- 29357220
TI  - Allostery, Recognition of Nascent Peptidoglycan, and Cross-linking of the Cell
      Wall by the Essential Penicillin-Binding Protein 2x of Streptococcus pneumoniae.
AB  - Transpeptidases, members of the penicillin-binding protein (PBP) families,
      catalyze cross-linking of the bacterial cell wall. This transformation is
      critical for the survival of bacteria, and it is the target of inhibition by beta
      lactam antibiotics. We report herein our structural insights into catalysis by
      the essential PBP2x of Streptococcus pneumoniae by disclosing a total of four X
      ray structures, two computational models based on the crystal structures, and
      molecular-dynamics simulations. The X-ray structures are for the apo PBP2x, the
      enzyme modified covalently in the active site by oxacillin (a penicillin
      antibiotic), the enzyme modified by oxacillin in the presence of a synthetic
      tetrasaccharide surrogate for the cell-wall peptidoglycan, and a noncovalent
      complex of cefepime (a cephalosporin antibiotic) bound to the active site. A
      prerequisite for catalysis by transpeptidases, including PBP2x, is the molecular
      recognition of nascent peptidoglycan strands, which harbor pentapeptide stems. We
      disclose that the recognition of nascent peptidoglycan by PBP2x takes place by
      complexation of one pentapeptide stem at an allosteric site located in the PASTA
      domains of this enzyme. This binding predisposes the third pentapeptide stem in
      the same nascent peptidoglycan strand to penetration into the active site for the
      turnover events. The complexation of the two pentapeptide stems in the same
      peptidoglycan strand is a recognition motif for the nascent peptidoglycan,
      critical for the cell-wall cross-linking reaction.

PMID- 29357221
TI  - Protein Labeling in Live Cells for Immunological Applications.
AB  - Protein labeling is often an important aspect of immunological experiments, as it
      allows observation of cellular processes, including protein synthesis and
      trafficking. Many protein labeling methods require permeabilization and fixation
      of cells, damaging the cells and preventing observation of processes in real
      time. However, a number of bioconjugation techniques allow protein labeling
      inside living cells to allow visualization of cellular processes as they occur
      and to facilitate retrieval of desired proteins. In this Topical Review, we
      describe bioconjugation methods that allow specific labeling of intracellular
      proteins of interest and discuss their applications to immunological studies. We
      focus on protein fusions, biotinylation, fluorescein arsenical helix binder
      (FlAsH) and resorufin arsenical helix binder (ReAsH) labeling, and tetrazine
      ligation.

PMID- 29357222
TI  - Piezotronic Effect on Rashba Spin-Orbit Coupling in a ZnO/P3HT Nanowire Array
      Structure.
AB  - A key concept in the emerging field of spintronics is the voltage-gate control of
      spin precession via the effective magnetic field generated by the Rashba spin
      orbit coupling (SOC). Traditional external gate voltage usually needs a power
      supply, which can easily bring about background noise or lead to a short circuit
      in measurement, especially for nanoscale spintronic devices. Here, we present a
      study on the circular photogalvanic effect (CPGE) in a ZnO/P3HT nanowire array
      structure with the device excited under oblique incidence. We demonstrate that a
      strong Rashba SOC is induced by the structure inversion asymmetry of the ZnO/P3HT
      heterointerface. We show that the Rashba SOC can be effectively tuned by inner
      crystal piezo-potential created inside the ZnO nanowires instead of an externally
      applied voltage. The piezo-potential can not only ensure the stability of future
      spin-devices under a static pressure or strain but also work without the need of
      extra energy; hence this room-temperature generation and piezotronic effect
      control of spin photocurrent demonstrate a potential application in large-scale
      flexible spintronics in piezoelectric nanowire systems.

PMID- 29357223
TI  - Iron-Based Metal-Organic Framework with Hydrophobic Quadrilateral Channels for
      Highly Selective Separation of Hexane Isomers.
AB  - A novel iron-based microporous metal-organic framework built of trinuclear iron
      clusters [Fe3(MU3-O)(COO)6] and 2,2-bis(4-carboxyphenyl)-hexafluoropropane
      (6FDCA) has been prepared by solvothermal synthesis. It exhibits excellent
      chemical stability and strong hydrophobic character. More importantly, this
      material is capable of separating hexane isomers with good separation performance
      on the basis of a kinetically controlled process, making it a promising candidate
      for improving the research octane number of gasoline.

PMID- 29357225
TI  - Short-Term Plasticity and Long-Term Potentiation in Artificial Biosynapses with
      Diffusive Dynamics.
AB  - The development of electronic devices possessing the functionality of biological
      synapses is a crucial step toward replicating the capabilities of the human
      brain. Of the various materials that have been used to realize artificial
      synapses, renewable natural materials have the advantages of being abundant,
      inexpensive, biodegradable, and ecologically benign. In this study, we report a
      biocompatible artificial synapse based on a matrix of the biopolymer iota
      carrageenan (iota-car), which exploits Ag dynamics. This artificial synapse
      emulates the short-term plasticity (STP), paired-pulse facilitation (PPF), and
      transition from STP to long-term potentiation (LTP) of a biological synapse. The
      above-mentioned characteristics are realized by exploiting the similarities
      between the Ag dynamics in the iota-car matrix and the Ca2+ dynamics in a
      biological synapse. By demonstrating a method that uses biomaterials and Ag
      dynamics to emulate synaptic functions, this study confirms that iota-car has the
      potential for constructing neuromorphic systems that use biocompatible artificial
      synapses.

PMID- 29357224
TI  - Relative Quantitation of Neuropeptides at Multiple Developmental Stages of the
      American Lobster Using N, N-Dimethyl Leucine Isobaric Tandem Mass Tags.
AB  - Neuromodulators and neurotransmitters play important roles in neural network
      development. The quantitative changes of these signaling molecules often reflect
      their regulatory roles in physiological processes. Currently, several commercial
      tags (e.g., iTRAQ and TMT) have been widely used in proteomics. With reduced cost
      and higher labeling efficiency, we employed a set of custom-developed N, N
      dimethyl leucine (DiLeu) 4-plex isobaric tandem mass tags as an attractive
      alternative for the relative quantitation of neuropeptides in brain tissue of
      American lobster Homarus americanus at multiple developmental stages. A general
      workflow for isobaric labeling of neuropeptides followed by LC-MS/MS analysis has
      been developed, including optimized sample handling procedures. Overall, we were
      able to quantify 18 trace-amount neuropeptides from 6 different families using a
      single adult brain as a control. The quantitation results indicated that the
      expressions of different neuropeptide families had significant changes over
      distinct developmental stages. Additionally, our data revealed intriguing
      elevated expression of neuropeptides in the early juvenile development stage. The
      methodology presented here advanced the workflow of DiLeu as an alternative
      labeling approach and the application of DiLeu-based quantitative peptidomics,
      which can be extended to areas beyond neuroscience.

PMID- 29357226
TI  - Silver Nanoparticles Impair Retinoic Acid-Inducible Gene I-Mediated Mitochondrial
      Antiviral Immunity by Blocking the Autophagic Flux in Lung Epithelial Cells.
AB  - Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially
      used as an alternative to antivirals to treat human infectious diseases,
      especially influenza virus infections where antivirals have generally proven
      unsuccessful. However, concerns about the use of AgNPs on humans arise from their
      potential toxicity, although mechanisms are not well-understood. We show here, in
      the context of an influenza virus infection of lung epithelial cells, that AgNPs
      down-regulated influenza induced CCL-5 and -IFN-beta release (two cytokines
      important in antiviral immunity) through RIG-I inhibition, while enhancing IL-8
      production, a cytokine important for mobilizing host antibacterial responses.
      AgNPs activity was independent of coating and was not observed with gold
      nanoparticles. Down-stream analysis indicated that AgNPs disorganized the
      mitochondrial network and prevented the antiviral IRF-7 transcription factor
      influx into the nucleus. Importantly, we showed that the modulation of RIG-I-IRF
      7 pathway was concomitant with inhibition of either classical or alternative
      autophagy (ATG-5- and Rab-9 dependent, respectively), depending on the epithelial
      cell type used. Altogether, this demonstration of a AgNPs-mediated functional
      dichotomy (down-regulation of IFN-dependent antiviral responses and up-regulation
      of IL-8-dependent antibacterial responses) may have practical implications for
      their use in the clinic.

PMID- 29357228
TI  - Scalable High-Performance Ultraminiature Graphene Micro-Supercapacitors by a
      Hybrid Technique Combining Direct Writing and Controllable Microdroplet Transfer.
AB  - Miniaturization of energy storage devices can significantly decrease the overall
      size of electronic systems. However, this miniaturization is limited by the
      reduction of electrode dimensions and the reproducible transfer of small
      electrolyte drops. This paper reports first a simple scalable direct writing
      method for the production of ultraminiature microsupercapacitor (MSC) electrodes,
      based on femtosecond laser reduced graphene oxide (fsrGO) interlaced pads. These
      pads, separated by 2 MUm spacing, are 100 MUm long and 8 MUm wide. A second stage
      involves the accurate transfer of an electrolyte microdroplet on top of each
      individual electrode, which can avoid any interference of the electrolyte with
      other electronic components. Abundant in-plane mesopores in fsrGO induced by a fs
      laser together with ultrashort interelectrode spacing enables MSCs to exhibit a
      high specific capacitance (6.3 mF cm-2 and 105 F cm-3) and ~100% retention after
      1000 cycles. An all graphene resistor-capacitor (RC) filter is also constructed
      by combining the MSC and a fsrGO resistor, which is confirmed to exhibit highly
      enhanced performance characteristics. This new hybrid technique combining fs
      laser direct writing and precise microdroplet transfer easily enables scalable
      production of ultraminiature MSCs, which is believed to be significant for
      practical application of micro-supercapacitor microelectronic systems.

PMID- 29357229
TI  - Slanted Functional Gradient Micropillars for Optimal Bioinspired Dry Adhesion.
AB  - For biologically inspired dry adhesives, the fibrillar structure of the surface
      requires sufficient flexibility to form contacts and meanwhile high rigidity to
      maintain stability. This fundamental conflict has greatly hindered the advance of
      synthetic adhesives toward mass-scale and practical applications, where adhesion
      is desired to be simultaneously strong, durable, directional, and roughness
      adaptive. In this work, we overcome such a long-term challenge by developing
      fibrillar structures that combine both slanted geometry and gradient material of
      micropillars. The termed slanted functional gradient pillars (s-FGPs), fabricated
      by a magnetically assisted mold replication technique, exhibit flexible tips for
      contacts, gradually stiffened stalks for reinforcement, slanted structure to give
      rise to anisotropy, and high aspect ratio (AR) to facilitate surface adaptation.
      We demonstrate that the material and structure of the s-FGPs complement each
      other, synergetic effects of which result in a multifunctional combination of
      adhesion properties including high strength (~9 N/cm2 in shear), ultradurability
      (over 200 cycles of attachment/detachment without adhesion degradation), super
      anisotropy (anisotropic ratio of ~7), and good adaptability to rough surfaces.
      The s-FGPs not only step forward the bioinspired adhesion toward optimized
      designs and performances for practical applications but may also open up other
      concepts for various high-AR and structurally stable fibrillar surfaces with
      emerging functionalities and applications in the fields of self-cleaning,
      superhydrophobicity, biosensors, energy harvesting, etc.

PMID- 29357227
TI  - Direct Observation of Oligomerization by Single Molecule Fluorescence Reveals a
      Multistep Aggregation Mechanism for the Yeast Prion Protein Ure2.
AB  - The self-assembly of polypeptides into amyloid structures is associated with a
      range of increasingly prevalent neurodegenerative diseases as well as with a
      select set of functional processes in biology. The phenomenon of self-assembly
      results in species with dramatically different sizes, from small oligomers to
      large fibrils; however, the kinetic relationship between these species is
      challenging to characterize. In the case of prion aggregates, these structures
      can self-replicate and act as infectious agents. Here we use single molecule
      spectroscopy to obtain quantitative information on the oligomer populations
      formed during aggregation of the yeast prion protein Ure2. Global analysis of the
      aggregation kinetics reveals the molecular mechanism underlying oligomer
      formation and depletion. Quantitative characterization indicates that the
      majority of Ure2 oligomers are relatively short-lived, and their rate of
      dissociation is much higher than their rate of conversion into growing fibrils.
      We identify an initial metastable oligomer, which can subsequently convert into a
      structurally distinct oligomer, which in turn converts into growing fibrils. We
      also show that fragmentation is responsible for the autocatalytic self
      replication of Ure2 fibrils, but that preformed fibrils do not promote oligomer
      formation, indicating that secondary nucleation of the type observed for peptides
      and proteins associated with neurodegenerative disease does not occur at a
      significant rate for Ure2. These results establish a framework for elucidating
      the temporal and causal relationship between oligomers and larger fibrillar
      species in amyloid forming systems, and provide insights into why functional
      amyloid systems are not toxic to their host organisms.

PMID- 29357230
TI  - In Vivo Coating of Bacterial Magnetic Nanoparticles by Magnetosome Expression of
      Spider Silk-Inspired Peptides.
AB  - Magnetosomes are natural magnetic nanoparticles with exceptional properties that
      are synthesized in magnetotactic bacteria by a highly regulated biomineralization
      process. Their usability in many applications could be further improved by
      encapsulation in biocompatible polymers. In this study, we explored the
      production of spider silk-inspired peptides on magnetosomes of the
      alphaproteobacterium Magnetospirillum gryphiswaldense. Genetic fusion of
      different silk sequence-like variants to abundant magnetosome membrane proteins
      enhanced magnetite biomineralization and caused the formation of a proteinaceous
      capsule, which increased the colloidal stability of isolated particles.
      Furthermore, we show that spider silk peptides fused to a magnetosome membrane
      protein can be used as seeds for silk fibril growth on the magnetosome surface.
      In summary, we demonstrate that the combination of two different biogenic
      materials generates a genetically encoded hybrid composite with engineerable new
      properties and enhanced potential for various applications.

PMID- 29357231
TI  - Structural Articulation of Biochemical Reactions Using Restrained Geometries and
      Topology Switching.
AB  - A strategy named "restrained geometries and topology switching" (RGATS) is
      presented to obtain detailed trajectories for complex biochemical reactions using
      molecular mechanics (MM) methods. It enables prediction of realistic dynamical
      pathways for chemical reactions, especially for accurately characterizing the
      structural adjustments of highly complex environments to any proximal biochemical
      reaction. It can be used to generate reactive conformations, model stepwise or
      concerted reactions in complex environments, and probe the influence of changes
      in the environment. Its ability to take reactively nonoptimal conformations and
      generate favorable starting conformations for a biochemical reaction is
      illustrated for a proton transfer between two model compounds. Its ability to
      study concerted reactions in explicit solvent is illustrated using proton
      transfers between an ammonium ion and two conserved histidines in an ammonia
      transporter channel embedded in a lipid membrane. Its ability to characterize the
      changes induced by subtle differences in the active site environment is
      illustrated using nucleotide addition by a DNA polymerase in the presence of two
      versus three Mg2+ ions. RGATS can be employed within any MM program and requires
      no additional software implementation. This allows the full assortment of
      computational methods implemented in all available MM programs to be used to
      tackle virtually any question about biochemical reactions that is answerable
      without using a quantum mechanical (QM) model. It can also be applied to generate
      reasonable starting structures for more detailed and expensive QM or QM/MM
      methods. In particular, this strategy enables rapid prediction of reactant,
      intermediary, or product state structures in any macromolecular context, with the
      only requirement being that the structure in any one of these states is either
      known or can be accurately modeled.

PMID- 29357232
TI  - Quantum Chemical Examination of the Sequential Halogen Incorporation Scheme for
      the Modeling of Speciation of I/Br/Cl-Containing Trihalomethanes.
AB  - The recently developed three-step ternary halogenation model interprets the
      incorporation of chlorine, bromine, and iodine ions into natural organic matter
      (NOM) and formation of iodine-, bromine-, and chlorine-containing trihalomethanes
      (THMs) based on the competition of iodine, bromine, and chlorine species at each
      node of the halogenation sequence. This competition is accounted for using the
      dimensionless ratios (denoted as gamma) of kinetic rates of reactions of the
      initial attack sites or halogenated intermediates with chlorine, bromine, and
      iodine ions. However, correlations between the model predictions made and
      mechanistic aspects of the incorporation of halogen species need to be
      ascertained in more detail. In this study, quantum chemistry calculations were
      first used to probe the formation mechanism of 10 species of Cl-/Br-/I- THMs. The
      HOMO energy (EHOMO) of each mono-, bi-, or trihalomethanes were calculated by
      B3LYP method in Gaussian 09 software. Linear correlations were found to exist
      between the logarithms of experimentally determined kinetic preference
      coefficients gamma reported in prior research and, on the other hand, differences
      of EHOMO values between brominated/iodinated and chlorinated halomethanes. One
      notable exception from this trend was that observed for the incorporation of
      iodine into mono- and di-iodinated intermediates. These observations confirm the
      three-step halogen incorporation sequence and the factor gamma in the statistical
      model. The combined use of quantum chemistry calculations and the ternary
      sequential halogenation model provides a new insight into the microscopic nature
      of NOM-halogen interactions and the trends seen in the behavior of gamma factors
      incorporated in the THM speciation models.

PMID- 29357233
TI  - Preclinical Explorative Assessment of Dimethyl Fumarate-Based Biocompatible
      Nanolipoidal Carriers for the Management of Multiple Sclerosis.
AB  - Multiple sclerosis (MS) is a neurodegenerative disease in which myelin sheath
      damage occurs due to internal and external factors. MS especially affects the
      young population. Dimethyl fumarate (DMF) is a promising agent for MS treatment,
      although it is associated with concerns such as poor brain permeation, multiple
      dosing, and gastrointestinal flushing. The present study attempts to evaluate the
      preclinical performance of specially designed DMF-based lipoidal nanoparticles in
      a cuprizone-induced demyelination model in rodents. The studies proved the
      efficacy of lipid-based nanoparticles containing DMF in a once-a-day dosage
      regimen over that of thrice-a-day plain DMF administration on crucial parameters
      like motor coordination, grip strength, mortality, body weight, and locomotor
      activity. However, neither blank lipid nor blank neuroprotective (vitamins A, D,
      and E) loaded nanoparticles were able to elicit any desirable behavioral
      response. Histopathological studies showed that the designed once-a-day DMF
      nanomedicines were well tolerated and rejuvenated the myelin sheath vis-a-vis the
      plain DMF thrice-a-day regimen. These findings provide proof of concept for a
      biocompatible nanomedicine for MS with tremendous promise for effective brain
      delivery and patient compliance on the grounds of a reduction in the dosage
      frequency.

PMID- 29357234
TI  - Biomimetic Nanosponges for Treating Antibody-Mediated Autoimmune Diseases.
AB  - Autoimmune diseases are characterized by overactive immunity, where the body's
      defense system launches an attack against itself. If left unchecked, this can
      result in the destruction of healthy tissue and significantly affect patient well
      being. In the case of type II autoimmune hypersensitivities, autoreactive
      antibodies attack the host's own cells or extracellular matrix. Current clinical
      treatment modalities for managing this class of disease are generally nonspecific
      and face considerable limitations. In this Topical Review, we cover emerging
      therapeutic strategies, with an emphasis on novel nanomedicine platforms.
      Specifically, the use of biomimetic cell membrane-coated nanosponges that are
      capable of specifically binding and neutralizing pathological antibodies will be
      explored. There is significant untapped potential in the application of
      nanotechnology for the treatment of autoimmune diseases, and continued
      development along this line may help to eventually change the clinical landscape.

PMID- 29357235
TI  - Mobility of Water and Polymer Species and Rheological Properties of
      Supramolecular Polypseudorotaxane Gels Suitable for Bone Regeneration.
AB  - The aim of this work was to prepare polypseudorotaxane-based supramolecular gels
      combining alphaCD with two temperature-responsive copolymers of different
      architecture (i.e., linear poloxamer P and X-shaped poloxamine T), at the lowest
      concentration as possible to form syringeable depots, and to shed light on the
      self-diffusion and spatial closeness of all components (including water) which in
      turn may determine the cooperative self-assembly phenomena and the performance of
      the gels at the macroscopic level. The exchange rate between bound water and bulk
      water was measured with a novel NMR experiment Water Diffusion Exchange-Diffusion
      Optimized Spectroscopy (WDE-DOSY). Polypseudorotaxane formation caused opposite
      effects on the mobility of alphaCD species (decreased) and internal water
      (increased) but did not affect PPO-water interaction. Consequently, designed
      ternary P/T/alphaCD supramolecular gels exhibited in situ gelling at body
      temperature could host large amounts of PLA/PLGA microspheres and behaved as
      porous 3D-scaffolds for mesenchymal stem cells (MSCs) supporting their osteogenic
      differentiation. Interestingly, the gels withstood freeze-drying and
      reconstitution with minor changes in inner structure and rheological properties.
      The gathered information may help to understand better the supramolecular gels
      and provide tools for the rational design of syringeable bone scaffolds that can
      simultaneously accommodate cells and drug microcarriers for efficient tissue
      regeneration.

PMID- 29357237
TI  - A Predictive Approach for the Optical Control of Carbonic Anhydrase II Activity.
AB  - Optogenetics and photopharmacology are powerful approaches to investigating
      biochemical systems. While the former is based on genetically encoded
      photoreceptors that utilize abundant chromophores, the latter relies on synthetic
      photoswitches that are either freely diffusible or covalently attached to
      specific bioconjugation sites, which are often native or engineered cysteines.
      The identification of suitable cysteine sites and appropriate linkers for
      attachment is generally a lengthy and cumbersome process. Herein, we describe an
      in silico screening approach that is designed to propose a small number of
      optimal combinations. By applying this computational approach to human carbonic
      anhydrase and a set of three photochromic tethered ligands, the number of
      potential site-ligand combinations was narrowed from over 750 down to 6, which we
      then evaluated experimentally. Two of these six combinations resulted in light
      responsive human Carbonic Anhydrases (LihCAs), which were characterized with
      enzymatic activity assays, mass spectrometry, and X-ray crystallography. Our
      study also provides insights into the reactivity of cysteines toward maleimides
      and the hydrolytic stability of the adducts obtained.

PMID- 29357236
TI  - Templated Formation of Luminescent Virus-like Particles by Tailor-Made Pt(II)
      Amphiphiles.
AB  - Virus-like particles (VLPs) have been created from luminescent Pt(II) complex
      amphiphiles, able to form supramolecular structures in water solutions, that can
      be encapsulated or act as templates of cowpea chlorotic mottle virus capsid
      proteins. By virtue of a bottom-up molecular design, icosahedral and
      nonicosahedral (rod-like) VLPs have been constructed through diverse pathways,
      and a relationship between the molecular structure of the complexes and the shape
      and size of the VLPs has been observed. A deep insight into the mechanism for the
      templated formation of the differently shaped VLPs was achieved, by electron
      microscopy measurements (TEM and STEM) and bulk analysis (FPLC, DLS,
      photophysical investigations). Interestingly, the obtained VLPs can be visualized
      by their intense emission at room temperature, generated by the self-assembly of
      the Pt(II) complexes. The encapsulation of the luminescent species is further
      verified by their higher emission quantum yields inside the VLPs, which is due to
      the confinement effect of the protein cage. These hybrid materials demonstrate
      the potential of tailor-made supramolecular systems able to control the assembly
      of biological building blocks.

PMID- 29357238
TI  - First-Principles Parametrization of Polarizable Coarse-Grained Force Fields for
      Ionic Liquids.
AB  - We present an ab initio parametrization scheme for explicitly dipole-polarizable
      force fields for the simulation of molecular liquids. The scheme allows for, in
      principle, arbitrarily coarse-grained representations. All parameters in the
      force field are derived from first-principles, based on simple physical
      arguments. Only one fit parameter enters the parametrization, a global scaling
      factor for the size of the particles, which is adjusted to reproduce the
      experimental mass density. As important examples and for the first time,
      polarizable coarse-grained force fields are derived for 1-alkyl-3
      methylimidazolium cations with varying alkyl-chain lengths (alkyl = ethyl, butyl,
      hexyl) and hexafluorophosphate and tetrafluoroborate anions. Our findings are in
      good agreement with experimental results and results of further atomistic
      simulations. Hence, the force fields can be faithfully used where polarizability
      is expected to play a significant role, such as simulations of energy storage
      devices.

PMID- 29357239
TI  - A Lattice Kinetic Monte Carlo Solver for First-Principles Microkinetic Trend
      Studies.
AB  - Mean-field microkinetic models in combination with Bronsted-Evans-Polanyi like
      scaling relations have proven highly successful in identifying catalyst materials
      with good or promising reactivity and selectivity. Analysis of the microkinetic
      model by means of lattice kinetic Monte Carlo promises a faithful description of
      a range of atomistic features involving short-range ordering of species in the
      vicinity of an active site. In this paper, we use the "fruit fly" example
      reaction of CO oxidation on fcc(111) transition and coinage metals to motivate
      and develop a lattice kinetic Monte Carlo solver suitable for the numerically
      challenging case of vastly disparate rate constants. As a result, we show that
      for the case of infinitely fast diffusion and absence of adsorbate-adsorbate
      interaction it is, in fact, possible to match the prediction of the mean-field
      theory method and the lattice kinetic Monte Carlo method. As a corollary, we
      conclude that lattice kinetic Monte Carlo simulations of surface chemical
      reactions are most likely to provide additional insight over mean-field
      simulations if diffusion limitations or adsorbate-adsorbate interactions have a
      significant influence on the mixing of the adsorbates.

PMID- 29357240
TI  - Unlocking High-Salinity Desalination with Cascading Osmotically Mediated Reverse
      Osmosis: Energy and Operating Pressure Analysis.
AB  - Current practice of using thermally driven methods to treat hypersaline brines is
      highly energy-intensive and costly. While conventional reverse osmosis (RO) is
      the most efficient desalination technique, it is confined to purifying seawater
      and lower salinity sources. Hydraulic pressure restrictions and elevated energy
      demand render RO unsuitable for high-salinity streams. Here, we propose an
      innovative cascading osmotically mediated reverse osmosis (COMRO) technology to
      overcome the limitations of conventional RO. The innovation utilizes the novel
      design of bilateral countercurrent reverse osmosis stages to depress the
      hydraulic pressure needed by lessening the osmotic pressure difference across the
      membrane, and simultaneously achieve energy savings. Instead of the 137 bar
      required by conventional RO to desalinate 70 000 ppm TDS hypersaline feed, the
      highest operating pressure in COMRO is only 68.3 bar (-50%). Furthermore, up to
      ~17% energy saving is attained by COMRO (3.16 kWh/m3, compared to 3.79 kWh/m3
      with conventional RO). When COMRO is employed to boost the recovery of seawater
      desalination to 70% from the typical 35-50%, energy savings of up to ~33% is
      achieved (2.11 kWh/m3, compared to 3.16 kWh/m3 with conventional RO). Again,
      COMRO can operate at a moderate hydraulic pressure of 80 bar (25% lower than 113
      bar of conventional RO). This study highlights the encouraging potential of
      energy-efficient COMRO to access unprecedented high recovery rates and treat
      hypersaline brines at moderate hydraulic pressures, thus extending the
      capabilities of membrane-based technologies for high-salinity desalination.

PMID- 29357241
TI  - Hydrolysis before Stir-Frying Increases the Isothiocyanate Content of Broccoli.
AB  - Broccoli is found to be a good source of glucosinolates, which can be hydrolyzed
      by endogenous myrosinase to obtain chemopreventive isothiocyanates (ITCs); among
      them, sulforaphane (SF) is the most important agent. Studies have shown that
      cooking greatly affects the levels of SF and total ITCs in broccoli. However, the
      stability of these compounds during cooking has been infrequently examined. In
      this study, we proved that the half-lives of SF and total ITCs during stir-frying
      were 7.7 and 5.9 min, respectively, while the myrosinase activity decreased by
      80% after stir-frying for 3 min; SF and total ITCs were more stable than
      myrosinase. Thus, the contents of SF and total ITCs decreased during stir-frying
      largely because myrosinase was destroyed. Subsequently, it was confirmed that
      compared to direct stir-frying, hydrolysis of glucosinolates in broccoli for 90
      min followed by stir-frying increased the SF and total ITC concentration by 2.8
      and 2.6 times, respectively. This method provides large quantities of beneficial
      ITCs even after cooking.

PMID- 29357242
TI  - Out-of-Register Abeta42 Assemblies as Models for Neurotoxic Oligomers and
      Fibrils.
AB  - We propose a variant of the recently found S-shaped Abeta1-42-motif that is
      characterized by out-of-register C-terminal beta-strands. We show that chains
      with this structure can form not only fibrils that are compatible with the NMR
      signals but also barrel-shaped oligomers that resemble the ones formed by the
      much smaller cylindrin peptides. By running long all-atom molecular dynamics
      simulations at physiological temperatures with an explicit solvent, we study the
      stability of these constructs and show that they are plausible models for
      neurotoxic oligomers. After analyzing the transitions between different
      assemblies, we suggest a mechanism for amyloid formation in Alzheimer's disease.

PMID- 29357244
TI  - Detection of Anomalous Dynamics for a Single Water Molecule.
AB  - Water dynamics is of predominant importance in life, and it plays a critical role
      in chemical and biological systems. Many studies have reported nonbulk and
      anomalous dynamics of water molecules; however, a general method to detect the
      anomalous dynamics is yet to be established. Here, we develop a detection
      approach for the anomalous dynamics of a water molecule. Using a time series of
      the dipole vector of a water molecule, our approach achieves single-molecule
      detection of the anomalous dynamics for all water molecules in the system.
      Moreover, our approach quantifies the anomalous dynamics of a water molecule,
      which enables users to compare between different systems. In addition to the
      applicability, our approach has computational efficiency because it never
      calculates interactions with any other molecules. Experiments on five different
      systems of molecular dynamics simulations illustrate that our approach
      successfully detects the change points of water-molecule dynamics. These results
      demonstrate that our approach is a useful tool and provides a better
      understanding of dynamics of water molecules.

PMID- 29357243
TI  - A GPU-Accelerated Parameter Interpolation Thermodynamic Integration Free Energy
      Method.
AB  - There has been a resurgence of interest in free energy methods motivated by the
      performance enhancements offered by molecular dynamics (MD) software written for
      specialized hardware, such as graphics processing units (GPUs). In this work, we
      exploit the properties of a parameter-interpolated thermodynamic integration (PI
      TI) method to connect states by their molecular mechanical (MM) parameter values.
      This pathway is shown to be better behaved for Mg2+ -> Ca2+ transformations than
      traditional linear alchemical pathways (with and without soft-core potentials).
      The PI-TI method has the practical advantage that no modification of the MD code
      is required to propagate the dynamics, and unlike with linear alchemical mixing,
      only one electrostatic evaluation is needed (e.g., single call to particle-mesh
      Ewald) leading to better performance. In the case of AMBER, this enables all the
      performance benefits of GPU-acceleration to be realized, in addition to unlocking
      the full spectrum of features available within the MD software, such as
      Hamiltonian replica exchange (HREM). The TI derivative evaluation can be
      accomplished efficiently in a post-processing step by reanalyzing the
      statistically independent trajectory frames in parallel for high throughput. We
      also show how one can evaluate the particle mesh Ewald contribution to the TI
      derivative evaluation without needing to perform two reciprocal space
      calculations. We apply the PI-TI method with HREM on GPUs in AMBER to predict p
      Ka values in double stranded RNA molecules and make comparison with experiments.
      Convergence to under 0.25 units for these systems required 100 ns or more of
      sampling per window and coupling of windows with HREM. We find that MM charges
      derived from ab initio QM/MM fragment calculations improve the agreement between
      calculation and experimental results.

PMID- 29357245
TI  - Optogenetics-Inspired Tunable Synaptic Functions in Memristors.
AB  - Two-terminal memristors with internal Ca2+-like dynamics can be used to
      faithfully emulate biological synaptic functions and have been intensively
      studied for neural network implementations. Inspired by the optogenetic technique
      that utilizes light to tune the Ca2+ dynamics and subsequently the synaptic
      plasticity, we develop a CH3NH3PbI3 (MAPbI3)-based memristor that exhibits light
      tunable synaptic behaviors. Specifically, we show that by increasing the
      formation energy of iodine vacancy (VI./VI*), light illumination can be used to
      control the VI./VI* generation and annihilation dynamics, resembling light
      controlled Ca2+ influx in biological synapses. We demonstrate that the memory
      formation and memory loss behaviors in the memristors can be modified by
      controlling the intensity and the wavelength of the illuminated light.
      Coincidence detection of electrical and light stimulations is also implemented in
      the memristive device with real-time (<=20 ms) response to light illumination.
      These results open options to modify the synaptic plasticity effects in memristor
      based neuromorphic systems and can lead to the development of electronic systems
      that can faithfully emulate diverse biological processes.

PMID- 29357246
TI  - Four-Component Polarization Propagator Calculations of Electron Excitations:
      Spectroscopic Implications of Spin-Orbit Coupling Effects.
AB  - A complete implementation of the polarization propagator based on the Dirac
      Coulomb Hamiltonian is presented and applied to excitation spectra of various
      systems. Hereby the effect of spin-orbit coupling on excitation energies and
      transition moments is investigated in detail. The individual perturbational
      contributions to the transition moments could now be separately analyzed for the
      first time and show the relevance of one- and two-particle terms. In some systems
      different contributions to the transition moments partially cancel each other and
      do not allow for simple predictions. For the outer valence spectrum of the
      H2Os(CO)4 complex a detailed final state analysis is performed explaining the
      sensitivity of the excitation spectrum to spin-orbit effects. Finally, technical
      issues of handling double group symmetry in the relativistic framework and
      methodological aspects of our parallel implementation are discussed.

PMID- 29357247
TI  - Physico-Chemical Characterization of Fine and Ultrafine Particles Emitted during
      Diesel Particulate Filter Active Regeneration of Euro5 Diesel Vehicles.
AB  - Diesel particulate filters (DPFs) are commonly employed in modern passenger cars
      to comply with current particulate matter (PM) emission standards. DPFs requires
      periodic regeneration to remove the accumulated matter. During the process, high
      concentration particles, in both nucleation and accumulation modes, are emitted.
      Here, we report new information on particle morphology and chemical composition
      of fine (FPs) and ultrafine particles (UFPs) measured downstream of the DPF
      during active regeneration of two Euro 5 passenger cars. The first vehicle was
      equipped with a close-coupled diesel oxidation catalyst (DOC) and noncatalyzed
      DPF combined with fuel borne catalyst and the second one with DOC and a catalyzed
      diesel particle filter (CDPF). Differences in PM emission profiles of the two
      vehicles were related to different after treatment design, regeneration
      strategies, and vehicle characteristics and mileage. Particles in the nucleation
      mode consisted of ammonium bisulfate, sulfate and sulfuric acid, suggesting that
      the catalyst desulfation is the key process in the formation of UFPs. Larger
      particles and agglomerates, ranging from 90 to 600 nm, consisted of carbonaceous
      material (soot and soot aggregates) coated by condensable material including
      organics, ammonium bisulfate and sulfuric acid. Particle emission in the
      accumulation mode was due to the reduced filtration efficiency (soot cake
      oxidation) throughout the regeneration process.

PMID- 29357248
TI  - Vertical Growth of Superconducting Crystalline Hollow Nanowires by He+ Focused
      Ion Beam Induced Deposition.
AB  - Novel physical properties appear when the size of a superconductor is reduced to
      the nanoscale, in the range of its superconducting coherence length (xi0). Such
      nanosuperconductors are being investigated for potential applications in
      nanoelectronics and quantum computing. The design of three-dimensional
      nanosuperconductors allows one to conceive novel schemes for such applications.
      Here, we report for the first time the use of a He+ focused-ion-beam-microscope
      in combination with the W(CO)6 precursor to grow three-dimensional
      superconducting hollow nanowires as small as 32 nm in diameter and with an aspect
      ratio (length/diameter) of as much as 200. Such extreme resolution is achieved by
      using a small He+ beam spot of 1 nm for the growth of the nanowires. As shown by
      transmission electron microscopy, they display grains of large size fitting with
      face-centered cubic WC1-x phase. The nanowires, which are grown vertically to the
      substrate, are felled on the substrate by means of a nanomanipulator for their
      electrical characterization. They become superconducting at 6.4 K and show large
      critical magnetic field and critical current density resulting from their quasi
      one-dimensional superconducting character. These results pave the way for future
      nanoelectronic devices based on three-dimensional nanosuperconductors.

PMID- 29357249
TI  - Ligand-Mediated Coating of Liposomes with Human Serum Albumin.
AB  - Coating liposome surfaces with human serum albumin (HSA) can improve the
      colloidal stability and prevent opsonization. HSA coating via specific binding
      with alkyl ligands is promising because although the ligand-mediated coating is
      relatively stable it can spontaneously exchange with fresh HSA. However, to
      achieve surface coating with HSA, multiple hydrophobic ligands must be exposed to
      an aqueous medium prior to binding with HSA. This presents a challenge, as
      hydrophobic ligands tend to be buried in the liposomal membrane. Here we present
      the first HSA modification of liposome surfaces via alkyl ligands. We found that
      a relatively short alkyl ligand, or a long alkyl ligand with a terminal
      carboxylate, could be exposed on the liposome surface without causing aggregation
      of the liposomes and these ligands could subsequently bind HSA. The resulting HSA
      coated liposomes were as inert as conventional PEGylated liposomes in terms of
      macrophage recognition.

PMID- 29357250
TI  - Discovery of 4-((7H-Pyrrolo[2,3-d]pyrimidin-4-yl)amino)-N-(4-((4-methylpiperazin
      1-yl)methyl)phenyl)-1H-pyrazole-3-carboxamide (FN-1501), an FLT3- and CDK-Kinase
      Inhibitor with Potentially High Efficiency against Acute Myelocytic Leukemia.
AB  - A series of 1-H-pyrazole-3-carboxamide derivatives have been designed and
      synthesized that exhibit excellent FLT3 and CDK inhibition and antiproliferative
      activities. A structure-activity-relationship study illustrates that the
      incorporation of a pyrimidine-fused heterocycle at position 4 of the pyrazole is
      critical for FLT3 and CDK inhibition. Compound 50 (FN-1501), which possesses
      potent inhibitory activities against FLT3, CDK2, CDK4, and CDK6 with IC50 values
      in the nanomolar range, shows antiproliferative activities against MV4-11 cells
      (IC50: 0.008 MUM), which correlates with the suppression of retinoblastoma
      phosphorylation, FLT3, ERK, AKT, and STAT5 and the onset of apoptosis. Acute
      toxicity studies in mice show that compound 50 (LD50: 186 mg/kg) is safer than
      AT7519 (32 mg/kg). In MV4-11 xenografts in a nude-mouse model, compound 50 can
      induce tumor regression at the dose of 15 mg/kg, which is more efficient than
      cytarabine (50 mg/kg). Taken together, these results demonstrate the potential of
      this unique compound for further development into a drug applied in acute-myeloid
      leukemia (AML) therapeutics.

PMID- 29357251
TI  - Salutaxel, a Conjugate of Docetaxel and a Muramyl Dipeptide (MDP) Analogue, Acts
      as Multifunctional Prodrug That Inhibits Tumor Growth and Metastasis.
AB  - Salutaxel (3) is a conjugate of docetaxel (7) and a muramyl dipeptide (MDP)
      analogue. Docetaxel (7) has been recognized as a highly active chemotherapeutic
      agent against various cancers. MDP and its analogues are powerful potentiators of
      the antitumor actions of various tumor-necrotizing agents. This article documents
      the discovery of compound 3 and presents pharmacological proof of its biological
      function in tumor-bearing mice. Drug candidate 3 was superior to compound 7 in
      its ability to prevent tumor growth and metastasis. Compound 3 suppressed myeloid
      derived suppressor cell (MDSC) accumulation in the spleens of tumor-bearing mice
      and decreased various serum inflammatory cytokines levels. Furthermore, compound
      3 antagonized the nucleotide-binding oligomerization domain-like receptor 1
      (NOD1) signaling pathway both in vitro and in vivo.

PMID- 29357252
TI  - Nature of Intramolecular Resonance Assisted Hydrogen Bonding in Malonaldehyde and
      Its Saturated Analogue.
AB  - The nature of resonance-assisted hydrogen bonds (RAHB) is still subject of an
      ongoing debate. We therefore analyzed the sigma and pi charge redistributions
      associated with the formation of intramolecular hydrogen bonds in malonaldehyde
      (MA) and its saturated analogue 3-hydroxypropanal (3-OH) and addressed the
      question whether there is a resonance assistance phenomenon in the sense of a
      synergistic interplay between the sigma and pi electron systems. Our quantum
      chemical calculations at the BP86/TZ2P level of theory show that the pi charge
      flow is indeed in line with the Lewis structure as proposed by the RAHB model.
      This typical rearrangement of charge is only present in the unsaturated system,
      and not in its saturated analogue. Resonance in the pi electron system assists
      the intramolecular hydrogen bond by reducing the hydrogen bond distance, and by
      providing an additional stabilizing component to the net bonding energy. The
      sigma orbital interaction plays an important role in the enhanced hydrogen bond
      strength in MA as well. However, there is no resonance assistance in the sense of
      an interplay between sigma charge transfer and pi polarization; sigma and pi
      contribute independently from each other.

PMID- 29357253
TI  - Dual Control of Molecular Conductance through pH and Potential in Single-Molecule
      Devices.
AB  - One of the principal aims of single-molecule electronics is to create practical
      devices out of individual molecules. Such devices are expected to play a
      particularly important role as novel sensors thanks to their response to wide
      ranging external stimuli. Here we show that the conductance of a molecular
      junction can depend on two independent stimuli simultaneously. Using a scanning
      tunnelling microscope break-junction technique (STM-BJ), we found that the
      conductance of 4,4'-vinylenedipyridine (44VDP) molecular junctions with Ni
      contacts depends on both the electrochemically applied gate voltage and the pH of
      the environment. Hence, not only can the Ni|44VDP|Ni junction function as a pH
      sensitive switch, but the value of the pH at which switching takes place can be
      tuned electrically. Furthermore, through the simultaneous control of pH and
      potential the STM-BJ technique delivers unique insight into the acid-base
      reaction, including the observation of discrete proton transfers to and from a
      single molecule.

PMID- 29357254
TI  - Manipulation of Nanoscale Intergranular Phases for High Proton Conduction and
      Decomposition Tolerance in BaCeO3 Polycrystals.
AB  - In many ion-conducting polycrystalline oxides, grain boundaries are generally
      accepted as rate-limiting obstacles to rapid ionic diffusion, often resulting in
      overall sluggish transport. Consequently, based on a precise understanding of the
      structural and compositional features at grain boundaries, systematic control of
      the polycrystalline microstructure is a key factor to achieve better ionic
      conduction performance. In this study, we clarify that a nanometer-thick
      amorphous phase at most grain boundaries in proton-conducting BaCeO3 polycrystals
      is responsible for substantial retardation of proton migration and moreover is
      very reactive with water and carbon dioxide gas. By a combination of atomic-scale
      chemical analysis and physical imaging, we demonstrate that highly densified
      BaCeO3 polycrystals free of a grain-boundary amorphous phase can be easily
      fabricated by a conventional ceramic process and show sufficiently high proton
      conductivity together with significantly improved chemical stability. These
      findings emphasize the value of direct identification of intergranular phases and
      subsequent manipulation of their distribution in ion-conducting oxide
      polycrystals.

PMID- 29357255
TI  - Hydrophobicity Varying with Temperature, Pressure, and Salt Concentration.
AB  - Temperature-, pressure-, and salt-concentration-induced variations in the
      solubility of small nonpolar solutes in aqueous solution and the corresponding
      variations in the solvent-induced pair attraction between such solute molecules
      are investigated. The variations in the solvation free energy of a solute and
      those in the solvent-induced pair attraction are well reproduced by a mean-field
      approximation in which the repulsive cores of solute molecules are treated as
      hard spheres and the mean-field energy of a solute molecule is taken to be the
      average potential energy that the solute molecule feels in solution. The
      mechanisms of variation in the solvation free energy and those of variation in
      the solvent-induced pair potential, with increasing temperature, pressure, and
      salt concentration, are clarified. Correlations between the solvation free energy
      and the solvent-induced pair potential at a contact distance in temperature,
      pressure, and salt concentration variations are near linear in any mode of
      variation, but the slope of the linear relation is dependent on the mode of
      variation and is determined by a ratio of the solvation thermodynamic quantities
      characteristic of each mode of variation.

PMID- 29357256
TI  - Measurement of Anisotropic Particle Interactions with Nonuniform ac Electric
      Fields.
AB  - Optical microscopy measurements are reported for single anisotropic polymer
      particles interacting with nonuniform ac electric fields. The present study is
      limited to conditions where gravity confines particles with their long axis
      parallel to the substrate such that particles can be treated using quasi-2D
      analysis. Field parameters are investigated that result in particles residing at
      either electric field maxima or minima and with long axes oriented either
      parallel or perpendicular to the electric field direction. By nonintrusively
      observing thermally sampled positions and orientations at different field
      frequencies and amplitudes, a Boltzmann inversion of the time-averaged
      probability of states yields kT-scale energy landscapes (including dipole-field,
      particle-substrate, and gravitational potentials). The measured energy landscapes
      show agreement with theoretical potentials using particle conductivity as the
      sole adjustable material property. Understanding anisotropic particle-field
      energy landscapes vs field parameters enables quantitative control of local
      forces and torques on single anisotropic particles to manipulate their position
      and orientation within nonuniform fields.

PMID- 29357258
TI  - Hamiltonian-Independent Generalization of the Fragment Excitation Difference
      Scheme.
AB  - The fragment excitation difference (FED) scheme is a useful method for
      calculating the complete diabatic couplings of various energy transfer systems.
      The lack of a good definition for the transformation of the transition density
      matrix to the off-diagonal FED matrix elements limits FED to single-excitation
      methods. We have developed a generalized FED scheme called the theta-optimized
      FED (theta-FED) scheme which does not require transforming the transition density
      matrices. In theta-FED, two states of interest are linearly transformed by a
      mixing angle theta into two mixed states. The excitation difference of each mixed
      state is evaluated and optimized numerically to determine the mixing angle. This
      approach allows for finding diabatic states and the corresponding couplings for a
      general set of Hamiltonians.

PMID- 29357259
TI  - Salt-Induced Thermoresponsivity of Cross-Linked Polymethoxyethylaminophosphazene
      Hydrogels: Energetics of the Volume Phase Transition.
AB  - Biodegradable hydrogels of cross-linked polymethoxyethylaminophosphazenes
      (PMOEAPs) of various cross-linking density and apparent subchain hydrophobicity
      were investigated by high-sensitivity differential scanning calorimetry and
      equilibrium swelling measurements. The volume phase transition of the hydrogels
      was found to be induced by salts of weak polybasic acids. The transition
      parameters were determined depending on the pH, phosphate concentration, cross
      linking density, and apparent hydrophobicity of the gels. The transition enthalpy
      increased three times and reached 60 J g-1 at the phosphate concentrations 5-100
      mM. The transition temperature decreased by 60  degrees C when the pH changed
      from 6 to 8. A decrease in the transition temperature (by ~20  degrees C) was
      achieved due to incorporation of 9.4 mol % of some alkyl groups into the gel
      subchains. The classic theory of the collapse of polymer gels coupled with the
      data of protein science on hydration energetics for various molecular surfaces
      reproduces correctly thermodynamics of the collapse of PMOEAP hydrogels.

PMID- 29357257
TI  - Polarizable Empirical Force Field for Halogen-Containing Compounds Based on the
      Classical Drude Oscillator.
AB  - The quality of the force field is crucial to ensure the accuracy of simulations
      used in molecular modeling, including computer-aided drug design (CADD). To
      perform more accurate modeling and simulations of halogenated molecules, in this
      study the polarizable force field based on the classical Drude oscillator model
      was extended to both aliphatic and aromatic systems using halogenated ethane and
      benzene model compounds for the halogens F, Cl, Br, and I. The force field
      parameters were optimized targeting quantum mechanical dipole moments, water
      interactions, and molecular polarizabilities as well as experimental observables,
      including enthalpies of vaporization, molecular volumes, hydration free energies,
      and dielectric constants. The developed halogenated polarizable force field is
      capable of reproducing QM relative energies and geometries of both halogen bonds
      and halogen-hydrogen bond donor interactions at an unprecedented level due to the
      inclusion of a virtual particle and anisotropic atomic polarizability on the
      halogen and, notably, the inclusion of Lennard-Jones parameters on the halogen
      Drude particle. The model was validated on the basis of its ability to accurately
      reproduce pure solvent properties for halogenated naphthalenes and alkanes,
      including species analogous to those used as refrigerants. Accordingly, it is
      anticipated that the model will be applicable for the study of halogenated
      derivatives in CADD as well as in other chemical and biophysical studies.

PMID- 29357260
TI  - Mitochondrial Targeted Doxorubicin-Triphenylphosphonium Delivered by Hyaluronic
      Acid Modified and pH Responsive Nanocarriers to Breast Tumor: in Vitro and in
      Vivo Studies.
AB  - Multidrug resistance (MDR) is the major obstacle for chemotherapy. In a previous
      study, we have successfully synthesized a novel doxorubicin (DOX) derivative
      modified by triphenylphosphonium (TPP) to realize mitochondrial delivery of DOX
      and showed the potential of this compound to overcome DOX resistance in MDA-MB
      435/DOX cells. (1) To introduce specificity for DOX-TPP to cancer cells, here we
      report on the conjugation of DOX-TPP to hyaluronic acid (HA) by hydrazone bond
      with adipic acid dihydrazide (ADH) as the acid-responsive linker, producing HA-
      hydra-DOX-TPP nanoparticles. Hyaluronic acid (HA) is a natural water-soluble
      linear glycosaminoglycan, which was hypothesized to increase the accumulation of
      nanoparticles containing DOX-TPP in the mitochondria of tumor cells upon systemic
      administration, overcoming DOX resistance, in vivo. Our results showed HA- hydra
      DOX-TPP to self-assemble to core/shell nanoparticles of good dispersibility and
      effective release of DOX-TPP from the HA- hydra-DOX-TPP conjugate in cancer
      cells, which was followed by enhanced DOX mitochondria accumulation. The HA-
      hydra-DOX-TPP nanoparticles also showed improved anticancer effects, better tumor
      cell apoptosis, and better safety profile compared to free DOX in MCF-7/ADR
      bearing mice.

PMID- 29357261
TI  - Food and Drug Administration-mandated Trials of Long-Acting beta-Agonist Safety
      in Asthma. Bang for the Buck?

PMID- 29357262
TI  - Symposium report on "Dynamic Methods For Improving Undergraduate Physiology
      Education": IUPS 38th World Congress.

PMID- 29357264
TI  - Ferreting Out the Role of Infection in Cystic Fibrosis Lung Disease.

PMID- 29357263
TI  - Reducing Harm Through Litigation Against Opioid Manufacturers? Lessons From the
      Tobacco Wars.

PMID- 29357265
TI  - Characterization of the "Frequent Exacerbator Phenotype" in Bronchiectasis.
AB  - RATIONALE: Exacerbations are key events in the natural history of bronchiectasis,
      but clinical predictors and outcomes of patients with frequently exacerbating
      disease are not well described. OBJECTIVES: To establish if there is a "frequent
      exacerbator phenotype" in bronchiectasis and the impact of exacerbations on long
      term clinical outcomes. METHODS: We studied patients with bronchiectasis enrolled
      from 10 clinical centers in Europe and Israel, with up to 5 years of follow-up.
      Patients were categorized by baseline exacerbation frequency (zero, one, two, or
      three or more per year). The repeatability of exacerbation status was assessed,
      as well as the independent impact of exacerbation history on hospitalizations,
      quality of life, and mortality. MEASUREMENTS AND MAIN RESULTS: A total of 2,572
      patients were included. Frequent exacerbations were the strongest predictor of
      future exacerbation frequency, suggesting a consistent phenotype. The incident
      rate ratios for future exacerbations were 1.73 (95% confidence interval [CI],
      1.47-2.02; P < 0.0001) for one exacerbation per year, 3.14 (95% CI, 2.70-3.66; P
      < 0.0001) for two exacerbations, and 5.97 (95% CI, 5.27-6.78; P < 0.0001) for
      patients with three or more exacerbations per year at baseline. Additional
      independent predictors of future exacerbation frequency were Haemophilus
      influenzae and Pseudomonas aeruginosa infection, FEV1, radiological severity of
      disease, and coexisting chronic obstructive pulmonary disease. Patients with
      frequently exacerbating disease had worse quality of life and were more likely to
      be hospitalized during follow-up. Mortality over up to 5 years of follow-up
      increased with increasing exacerbation frequency. CONCLUSIONS: The frequent
      exacerbator phenotype in bronchiectasis is consistent over time and shows high
      disease severity, poor quality of life, and increased mortality during follow-up.

PMID- 29357266
TI  - Genetic diversity of K-antigen gene clusters of Escherichia coli and their
      molecular typing using a suspension array.
AB  - Capsular polysaccharides (CPSs), or K-antigens, are the major surface antigens of
      Escherichia coli. More than 80 serologically unique K-antigens are classified
      into 4 groups (Groups 1-4) of capsules. Groups 1 and 4 contain the Wzy-dependent
      polymerization pathway and the gene clusters are in the order galF to gnd; Groups
      2 and 3 contain the ABC-transporter-dependent pathway and the gene clusters
      consist of 3 regions, regions 1, 2 and 3. Little is known about the variations
      among the gene clusters. In this study, 9 serotypes of K-antigen gene clusters
      (K2ab, K11, K20, K24, K38, K84, K92, K96, and K102) were sequenced and correlated
      with their CPS chemical structures. On the basis of sequence data, a K-antigen
      specific suspension array that detects 10 distinct CPSs, including the above 9
      CPSs plus K30, was developed. This is the first report to catalog the genetic
      features of E. coli K-antigen variations and to develop a suspension array for
      their molecular typing. The method has a number of advantages over traditional
      bacteriophage and serum agglutination methods and lays the foundation for
      straightforward identification and detection of additional K-antigens in the
      future.

PMID- 29357267
TI  - Variation in behavioral engagement during an active learning activity leads to
      differential knowledge gains in college students.
AB  - There are many pedagogical techniques used by educators in higher education;
      however, some techniques and activities have been shown to be more beneficial to
      student learning than others. Research has demonstrated that active learning and
      learning in which students cognitively engage with the material in a multitude of
      ways result in better understanding and retention. The aim of the present study
      was to determine which of three pedagogical techniques led to improvement in
      learning and retention in undergraduate college students. Subjects partook in one
      of three different types of pedagogical engagement: hands-on learning with a
      model, observing someone else manipulate the model, and traditional lecture-based
      presentation. Students were then asked to take an online quiz that tested their
      knowledge of the new material, both immediately after learning the material and 2
      wk later. Students who engaged in direct manipulation of the model scored higher
      on the assessment immediately after learning the material compared with the other
      two groups. However, there were no differences among the three groups when
      assessed after a 2-wk retention interval. Thus active learning techniques that
      involve direct interaction with the material can lead to learning benefits;
      however, how these techniques benefit long-term retention of the information is
      equivocal.

PMID- 29357268
TI  - A Moodle-based blended learning solution for physiology education in Montenegro:
      a case study.
AB  - This study evaluates the impact of web-based blended learning in the physiology
      course at the Faculty of Medicine, University of Montenegro. The two main goals
      of the study were: to determine the impact of e-learning on student success in
      mastering the course, and to assess user satisfaction after the introduction of e
      learning. The study compared a group of students who attended the physiology
      course before, with a group of students who attended the physiology course after
      the Moodle platform was fully implemented as an educational tool. Formative and
      summative assessment scores were compared between these two groups. The impact of
      high vs. low Moodle use on the assessment scores was analyzed. The satisfaction
      among Moodle users was assessed by the survey. The study found that attendance of
      face-to-face lectures had a positive impact on academic performance. The
      introduction of Moodle in the presented model of teaching increased interest of
      students, attendance of face-to-face lectures, as well as formative and summative
      scores. High frequency of Moodle use was not always associated with better
      academic performance, suggesting that the introduction of a new method of
      teaching was most likely equally accepted by low- and high-achieving students.
      Most of the students agreed that Moodle was easy to use and it complemented
      traditional teaching very well, but it could not completely replace traditional
      face-to-face lectures. The study supports continuing the use of web-based
      learning in a form of blended learning for physiology, as well as for other
      courses in medical education.

PMID- 29357269
TI  - Involving a real patient in the design and implementation of case-based learning
      to engage learners.
AB  - Real patients offer unique opportunities to develop authentic, engaging, and
      transformative learning experiences for students. Patients are widely employed to
      teach clinical and interpersonal skills in the clerkship phase of their medical
      education (M3-M4), but have not been extensively included in the preclinical
      curriculum (M1-M2) when students are focused on acquiring foundational biomedical
      science knowledge. To maximize learning and help students connect foundational
      and clinical science concepts to real-world clinical problems, we involved a real
      patient in the creation and implementation of a case-based learning (CBL)
      activity in our preclinical curriculum. Using the patient's narrative as a
      framework, the CBL addressed relevant aspects of physiology, pathophysiology,
      anatomy, pharmacology, and nutrition, as well as clinical care decisions, health
      literacy, and medical ethics. The intervention was implemented with the 2019 and
      2020 graduating medical school classes during the Gastrointestinal Systems course
      in the second year of our curriculum. The results of a survey revealed that,
      overall, a majority of the students agreed or strongly agreed that the activity
      increased engagement in class, increased the depth of discussion within their
      teams, increased the depth of discussion between teams, helped students to apply
      basic science concepts to the clinical material in the case, helped students
      better understand the disease processes described in the case, enhanced awareness
      of the complexity of patient care, provided an authentic learning experience, and
      elicited a feeling of empathy.

PMID- 29357270
TI  - The K-INBRE symposium: a 10-institution collaboration to improve undergraduate
      education.
AB  - The Kansas-IDeA Network of Biomedical Research Excellence (K-INBRE) is an
      infrastructure-building program funded by the National Institute of General
      Medical Sciences. Undergraduate education, through undergraduate research, is a
      key component of the program. The K-INBRE network includes 10 higher education
      institutions in Kansas and northern Oklahoma, with over 1,000 student
      participants in 16 yr. Since 2003, the K-INBRE has held an annual state-wide
      research symposium that includes national and regional speakers and provides a
      forum for undergraduates to give platform and poster presentations. The symposium
      is well attended by K-INBRE participants and has grown to a size of over 300
      participants per year from all 10 K-INBRE schools. Two surveys were distributed
      to students and mentors to assess the impact of the symposium on student
      learning. Surveys (153) were distributed to students who participated in K-INBRE
      from 2013 through 2015 with a 51% response rate. Mentors were surveyed with a
      response of 111 surveys out of 161. Survey results indicate that students and
      mentors alike find the symposium to be beneficial and enriching of the student
      experience. Almost 80% of student respondents indicated that their participation
      in the symposium fostered appreciation of research. In short, the K-INBRE
      symposium provides a unique opportunity for students to gain experience in
      collecting, preparing, and communicating research in a professional environment.
      The collaborative experience of the annual K-INBRE symposium, the impact it has
      on student learning, and how it has influenced the research culture at our 10
      institutions will be described.

PMID- 29357271
TI  - Using Hawkeye from the Avengers to communicate on the eye.
AB  - Superheroes, such as Iron Man, Captain America, Wonder Woman, Batman, and
      Hawkeye, have appeared in numerous films, displaying their range of incredible
      superpowers and abilities. Therefore, it is unsurprising that many people would
      not only wish to attain these powers, but also to learn about scientific
      accessibility to these powers. Popular culture characters such as superheroes can
      provide a unique platform for the communication of difficult scientific concepts.
      In the classroom, these characters can be used to communicate learning objectives
      to students in an interesting, fun, and accessible manner by taking advantage of
      student familiarity with the characters. Hawkeye, a member of the Avengers, is
      one such superhero who can be utilized by educators. His powers can be attributed
      in part to his advanced eyesight, which has physiological aspects in common with
      many birds of prey. Hence, Hawkeye can instigate discussion on the physiology of
      the human eye, while also allowing for comparison with other species, such as
      birds of prey, and reflection on advancements related to genetic engineering and
      wearable technologies. In addition, in my experience, Hawkeye has proven to be a
      highly suitable popular culture character for use in scientific communication and
      outreach.

PMID- 29357272
TI  - Characterization of Degree of Intestinal Fibrosis in Patients with Crohn Disease
      by Using Magnetization Transfer MR Imaging.
AB  - Purpose To evaluate the role of magnetization transfer (MT) magnetic resonance
      (MR) imaging for the characterization of intestinal fibrosis compared with
      contrast material-enhanced and diffusion-weighted MR imaging and its capability
      for differentiating fibrotic from inflammatory strictures in humans with Crohn
      disease (CD) by using surgical histopathologic analysis as the reference
      standard. Materials and Methods Institutional review board approval and informed
      consent were obtained for this prospective study. Abdominal MT imaging, contrast
      enhanced imaging, and diffusion-weighted imaging of 31 consecutive patients with
      CD were analyzed before elective surgery. The bowel wall MT ratio normalized to
      skeletal muscle, the apparent diffusion coefficient (ADC), and the percentage of
      enhancement gain were calculated; region-by-region correlations with the surgical
      specimen were performed to determine the histologic degree of fibrosis and
      inflammation. The performance of MT imaging was validated in five new patients.
      One-way analysis of variance test, Spearman rank correlation, and receiver
      operating characteristic curve were used for statistical analysis. Results
      Normalized MT ratios strongly correlated with fibrosis scores (r = 0.769; P =
      .000) but did not correlate with inflammation scores (r = -0.034; P = .740).
      Significant differences (F = 49.002; P = .000) in normalized MT ratios were found
      among nonfibrotic, mildly, moderately, and severely fibrotic walls. The
      normalized MT ratios of mixed fibrotic and inflammatory bowel walls were
      significantly higher than those of bowel walls with only inflammation present (t
      = -8.52; P = .000). A high accuracy of normalized MT ratios was shown with an
      area under the receiver operating characteristic curve (AUC) of 0.919 (P = .000)
      for differentiating moderately to severely fibrotic bowel walls from nonfibrotic
      and mildly fibrotic bowel walls, followed by ADC (AUC, 0.747; P = .001) and the
      percentage of enhancement gain (AUC, 0.592; P = .209). The sensitivity,
      specificity, and AUC of MT imaging for diagnosing moderate to severe fibrosis in
      the validation data set were 80% (12 of 15), 100% (three of three), and 0.9 (P =
      .033), respectively. Conclusion MT imaging outperforms ADC and contrast-enhanced
      imaging in detecting and distinguishing varying degrees of bowel fibrosis with or
      without coexisting inflammation. MT imaging could potentially be used as a method
      to differentiate fibrotic from inflammatory intestinal strictures in patients
      with CD. (c) RSNA, 2018 Online supplemental material is available for this
      article.

PMID- 29357273
TI  - Progressive Reduction in Gray Matter in Patients with Schizophrenia Assessed with
      MR Imaging by Using Causal Network Analysis.
AB  - Purpose To investigate the temporal and causal relationships of structural
      changes in the brain in patients with schizophrenia. Materials and Methods T1
      weighted magnetic resonance (MR) images of 97 patients with schizophrenia (29
      women; mean +/- standard deviation age, 41 years +/- 11.5; range, 16-66 years;
      illness duration, 16.3 years +/- 10.9; range, 0-50 years) and 126 age- and sex
      matched (38 years +/- 14.9; range, 18-68 years; 42 women) healthy control
      subjects were evaluated. The causal network of structural covariance was used to
      assess the causal relationships of structural changes in patients with
      schizophrenia. This was accomplished by applying Granger causality analysis to
      the morphometric T1-weighted images ranked according to duration of disease.
      Results With greater disease duration, reduction in gray matter volume began in
      the thalamus and progressed to the frontal lobe, and then to the temporal and
      occipital cortices as well and the cerebellum (P < .00001, false discovery rate
      corrected). The thalamus was shown to be the primary hub of the directional
      network and exhibited positive causal effects on the frontal, temporal, and
      occipital regions as well as on the cerebellum (P < .05, false discovery rate
      corrected). The frontal regions, which were identified to be transitional points,
      projected causal effects to the occipital lobe, temporal regions, and the
      cerebellum and received causal effects from the thalamus (P < .05, false
      discovery rate corrected). Conclusion Schizophrenia shows progression of gray
      matter abnormalities over time, with the thalamus as the primary hub and the
      frontal regions as prominent nodes. (c) RSNA, 2018 Online supplemental material
      is available for this article. An earlier incorrect version of this article
      appeared online. This article was corrected on March 5, 2018.

PMID- 29357274
TI  - Glioblastoma: Vascular Habitats Detected at Preoperative Dynamic Susceptibility
      weighted Contrast-enhanced Perfusion MR Imaging Predict Survival.
AB  - Purpose To determine if preoperative vascular heterogeneity of glioblastoma is
      predictive of overall survival of patients undergoing standard-of-care treatment
      by using an unsupervised multiparametric perfusion-based habitat-discovery
      algorithm. Materials and Methods Preoperative magnetic resonance (MR) imaging
      including dynamic susceptibility-weighted contrast material-enhanced perfusion
      studies in 50 consecutive patients with glioblastoma were retrieved. Perfusion
      parameters of glioblastoma were analyzed and used to automatically draw four
      reproducible habitats that describe the tumor vascular heterogeneity: high
      angiogenic and low-angiogenic regions of the enhancing tumor, potentially tumor
      infiltrated peripheral edema, and vasogenic edema. Kaplan-Meier and Cox
      proportional hazard analyses were conducted to assess the prognostic potential of
      the hemodynamic tissue signature to predict patient survival. Results Cox
      regression analysis yielded a significant correlation between patients' survival
      and maximum relative cerebral blood volume (rCBVmax) and maximum relative
      cerebral blood flow (rCBFmax) in high-angiogenic and low-angiogenic habitats (P <
      .01, false discovery rate-corrected P < .05). Moreover, rCBFmax in the
      potentially tumor-infiltrated peripheral edema habitat was also significantly
      correlated (P < .05, false discovery rate-corrected P < .05). Kaplan-Meier
      analysis demonstrated significant differences between the observed survival of
      populations divided according to the median of the rCBVmax or rCBFmax at the high
      angiogenic and low-angiogenic habitats (log-rank test P < .05, false discovery
      rate-corrected P < .05), with an average survival increase of 230 days.
      Conclusion Preoperative perfusion heterogeneity contains relevant information
      about overall survival in patients who undergo standard-of-care treatment. The
      hemodynamic tissue signature method automatically describes this heterogeneity,
      providing a set of vascular habitats with high prognostic capabilities. (c) RSNA,
      2018.

PMID- 29357275
TI  - Prognostic Value of Metabolic and Volumetric Parameters of FDG PET in Pediatric
      Osteosarcoma: A Hypothesis-generating Study.
AB  - Purpose To preliminarily assess the potential prognostic value of various
      fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET)
      parameters before, during, and after neoadjuvant chemotherapy (NCT). Materials
      and Methods Thirty-four patients with osteosarcoma were enrolled prospectively
      from 2008 to 2012 and underwent FDG PET/computed tomography (CT) imaging before
      (baseline scan), during (interim scan) and after NCT (posttherapy scan). The
      study was approved by the institutional review board and informed consent was
      received from patients. Maximum and peak standardized uptake value (SUVmax and
      SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were
      measured. Predictive value of FDG PET parameters for event-free survival (EFS)
      and overall survival (OS) were evaluated. Multivariable Cox regression analysis
      for EFS and OS was performed by using histologic response and initial presence of
      metastasis as covariates. Results At baseline scan, SUVpeak, MTV, and TLG were
      predictive of EFS (P = .006-.03) and OS (P = .001-.03) but not associated with
      histologic response. At interim and posttherapy scan, SUVmax, SUVpeak, MTV, and
      TLG were associated with histologic response (P = .0002-.04) and predictive of
      EFS (P = .004-.02) and OS (P = .001-.03). Multivariable Cox regression analysis
      revealed that the FDG PET parameters either at baseline, interim, or posttherapy
      were independently predictive of EFS and OS. In particular, baseline MTV was an
      independent predictor of EFS (hazard ratio, 5.0 [95% confidence interval {CI}:
      1.5, 16.8]) and OS (hazard ratio, 29.4 [95% CI: 2.2, 392.2]). Conclusion SUVpeak,
      MTV, and TLG either at baseline, interim, or posttherapy were predictive of EFS
      and OS and may be useful prognostic biomarkers for osteosarcoma. (c) RSNA, 2018
      Online supplemental material is available for this article.

PMID- 29357277
TI  - The distance decay of similarity in tropical rainforests. A spatial point
      processes analytical formulation.
AB  - In this paper we are concerned with the analytical description of the change in
      floristic composition (species turnover) with the distance between two plots of a
      tropical rainforest due to the clustering of the individuals of the different
      species. We describe the plant arrangement by a superposition of spatial point
      processes and in this framework we introduce an analytical function which
      represents the average spatial density of the Sorensen similarity between two
      infinitesimal plots at distance r. We see that the decay in similarity with the
      distance is essentially described by the pair correlation function of the
      superposed process and that it is governed by the most abundant species. We test
      our analytical model with empirical data obtained for the Barro Colorado Island
      and Pasoh rainforests. To this end we adopt the statistical estimator for the
      pair correlation function in Shimatani (2001) and we design a novel one for the
      Sorensen similarity. Furthermore, we test our analytical formula by modeling the
      forest study area with Neyman-Scott point processes. We conclude comparing the
      advantages of our approach with other ones existing in literature.

PMID- 29357276
TI  - Dynamic clustering of dynamin-amphiphysin helices regulates membrane constriction
      and fission coupled with GTP hydrolysis.
AB  - Dynamin is a mechanochemical GTPase essential for membrane fission during
      clathrin-mediated endocytosis. Dynamin forms helical complexes at the neck of
      clathrin-coated pits and their structural changes coupled with GTP hydrolysis
      drive membrane fission. Dynamin and its binding protein amphiphysin cooperatively
      regulate membrane remodeling during the fission, but its precise mechanism
      remains elusive. In this study, we analyzed structural changes of dynamin
      amphiphysin complexes during the membrane fission using electron microscopy (EM)
      and high-speed atomic force microscopy (HS-AFM). Interestingly, HS-AFM analyses
      show that the dynamin-amphiphysin helices are rearranged to form clusters upon
      GTP hydrolysis and membrane constriction occurs at protein-uncoated regions
      flanking the clusters. We also show a novel function of amphiphysin in size
      control of the clusters to enhance biogenesis of endocytic vesicles. Our
      approaches using combination of EM and HS-AFM clearly demonstrate new mechanistic
      insights into the dynamics of dynamin-amphiphysin complexes during membrane
      fission.

PMID- 29357279
TI  - Practice-related changes in eye movement strategy in healthy adults with
      simulated hemianopia.
AB  - The impact of visual field deficits such as hemianopia can be mitigated by eye
      movements that position the visual image within the intact visual field.
      Effective eye movement strategies are not observed in all patients, however, and
      it is not known whether persistent deficits are due to injury or to pre-existing
      individual differences. Here we examined whether repeated exposure to a search
      task with rewards for good performance would lead to better eye movement
      strategies in healthy individuals. Participants were exposed to simulated
      hemianopia during a search task in five testing sessions over five consecutive
      days and received monetary payment for improvements in search times. With
      practice, most participants made saccades that went further into the blind field
      earlier in search, specifically under conditions where little information about
      the target location would be gained by inspecting the sighted field. These
      changes in search strategy were correlated with reduced search times. This
      strategy improvement also generalised to a novel task, with better performance in
      naming objects in a photograph under conditions of simulated hemianopia after
      practice with visual search compared to a control group. However, even after five
      days, eye movements in most participants remained far from optimal. The results
      demonstrate the benefits, and limitations, of practice and reward in the
      development of effective coping strategies for visual field deficits.

PMID- 29357278
TI  - Social factors and aromatase gene expression during adult male-to-female sex
      change in captive leopard grouper Mycteroperca rosacea.
AB  - Social factors and aromatase gene expression in the leopard grouper Mycteroperca
      rosacea was studied when captive fish were separated by sex during the
      reproductive (April-June) and post-reproductive (July-September) seasons. Monosex
      females, monosex males, and mixed-sex, held in social sextet units were analyzed
      for sex steroids throughout confinement. At the end of the experiment, the gonad
      sex was defined by histology, and gonad and brain aromatase gene expressions were
      quantified. Only males held in the monosex social units changed sex. Histology
      showed one male remained unchanged, six were found in a transitional sexual
      stage, in which two had intersex-predominantly-testes, and four had a more
      defined intersex ovo-testes pattern, and 11 were immature de novo females
      (neofemales). Neofemales and most intersex fish did not survive. In spring, 11
      ketosterone showed a specific male profile, which suggests that male-to-female
      sex change was not triggered during the reproductive season. The low steroid
      levels in summer made it impossible to associate the sex change to a gonad
      hormonal shift; in September, gonad aromatase gene expression was not
      significantly different among groups. However, brain aromatase expression in
      intersex fish was significantly higher than monosex females, mixed-sex females,
      and neofemale groups. These results suggest that in the absence of female
      hormonal compounds, and at a time when male gonad steroidogenesis was diminished,
      the brain mediated male-to-male social-behavioral interactions, including stress,
      by increasing aromatization, resulting in derived intersex-male, which triggered
      more aromatization, followed by a sex change.

PMID- 29357280
TI  - Effectiveness of Neuromuscular Electrical Stimulation on Lower Limbs of Patients
      With Hemiplegia After Chronic Stroke: A Systematic Review.
AB  - OBJECTIVE: To investigate the effectiveness of neuromuscular electrical
      stimulation (NMES) with or without other interventions in improving lower limb
      activity after chronic stroke. DATA SOURCES: Electronic databases, including
      PubMed, EMBase, Cochrane Library, PEDro (Physiotherapy Evidence Database), and
      PsycINFO, were searched from the inception to January 2017. STUDY SELECTION: We
      selected the randomized controlled trials (RCTs) involving chronic stroke
      survivors with lower limb dysfunction and comparing NMES or combined with other
      interventions with a control group of no electrical stimulation treatment. DATA
      EXTRACTION: The primary outcome was defined as lower limb motor function, and the
      secondary outcomes included gait speed, Berg Balance Scale, timed Up and Go, 6
      minute walk test, Modified Ashworth Scale, and range of motion. DATA SYNTHESIS:
      Twenty-one RCTs involving 1481 participants were identified from 5759 retrieved
      articles. Pooled analysis showed that NMES had a moderate but statistically
      significant benefit on lower limb motor function (standard mean difference 0.42,
      95% confidence interval 0.26-0.58), especially when NMES was combined with other
      interventions or treatment time within either 6 or 12 weeks. NMES also had
      significant benefits on gait speed, balance, spasticity, and range of motion but
      had no significant difference in walking endurance after NMES. CONCLUSIONS: NMES
      combined with or without other interventions has beneficial effects in lower limb
      motor function in chronic stroke survivors. These data suggest that NMES should
      be a promising therapy to apply in chronic stroke rehabilitation to improve the
      capability of lower extremity in performing activities.

PMID- 29357281
TI  - Leflunomide: A promising drug with good antitumor potential.
AB  - Leflunomide, an inhibitor of dihydroorotase dehydrogenase and thereby pyrimidine
      synthesis, was approved for treatment of rheumatoid arthritis in 1998. During the
      following years, leflunomide was used in various preclinical studies as a
      potential cancer treatment; at the same time, more mechanisms underlying the
      anticancer effect of leflunomide were identified. Thus, leflunomide has been
      identified as a potent anticancer drug. This article summarizes the mechanisms as
      well as results of leflunomide in the evolving field of cancer therapy.

PMID- 29357282
TI  - Barcoded sequencing workflow for high throughput digitization of hybridoma
      antibody variable domain sequences.
AB  - Since the invention of Hybridoma technology by Milstein and Kohler in 1975, its
      application has greatly advanced the antibody discovery process. The technology
      enables both functional screening and long-term archival of the immortalized
      monoclonal antibody producing B cells. Despite the dependable cryopreservation
      technology for hybridoma cells, practicality of long-term storage has been
      outpaced by recent progress in robotics and automations, which enables routine
      identification of thousands of antigen specific hybridoma clones. Such throughput
      increase imposes two nascent challenges in the antibody discovery process, namely
      limited cryopreservation storage space and limited throughput in conventional
      antibody sequencing. We herein provide a barcoded sequencing workflow that
      utilizes next generation sequencing to expand the conventional sequencing
      capacity. Accompanied with the bioinformatics tools we describe, the barcoded
      sequencing workflow robustly reports unambiguous antibody sequences as confirmed
      with Sanger sequencing controls. In complement with the commonly accessible
      recombinant DNA technology, the barcoded sequencing workflow allows for high
      throughput digitization of the antibody sequences and provides an effective
      solution to the limitations imposed by physical storage and sequencing capacity.

PMID- 29357283
TI  - Perdeuteration of cholesterol for neutron scattering applications using
      recombinant Pichia pastoris.
AB  - Deuteration of biomolecules has a major impact on both quality and scope of
      neutron scattering experiments. Cholesterol is a major component of mammalian
      cells, where it plays a critical role in membrane permeability, rigidity and
      dynamics, and contributes to specific membrane structures such as lipid rafts.
      Cholesterol is the main cargo in low and high-density lipoprotein complexes (i.e.
      LDL, HDL) and is directly implicated in several pathogenic conditions such as
      coronary artery disease which leads to 17 million deaths annually. Neutron
      scattering studies on membranes or lipid-protein complexes exploiting contrast
      variation have been limited by the lack of availability of fully deuterated
      biomolecules and especially perdeuterated cholesterol. The availability of
      perdeuterated cholesterol provides a unique way of probing the structural and
      dynamical properties of the lipoprotein complexes that underly many of these
      disease conditions. Here we describe a procedure for in vivo production of
      perdeuterated recombinant cholesterol in lipid-engineered Pichia pastoris using
      flask and fed-batch fermenter cultures in deuterated minimal medium.
      Perdeuteration of the purified cholesterol was verified by mass spectrometry and
      its use in a neutron scattering study was demonstrated by neutron reflectometry
      measurements using the FIGARO instrument at the ILL.

PMID- 29357284
TI  - Reliability of a two-wavelength autofluorescence technique by Heidelberg
      Spectralis to measure macular pigment optical density in Asian subjects.
AB  - This study evaluates the accuracy of an objective two-wavelength fundus
      autofluorescence technique for the purpose of measuring the macular pigment
      optical density (MPOD) in Asian pigmented eyes. Potential differences between
      MPOD values obtained via autofluorescence technique and subjective
      heterochromatic photometry (HFP) were examined. Inter-examiner reproducibility
      between three examiners and test-retest reliability over five time points were
      also explored. Subjects were 27 healthy Japanese volunteers aged 24 to 58 (mean
      +/- standard deviation, 40.2 +/- 9.0) years. An MPOD module of the Spectralis
      MultiColor instrument configuration (Spectralis-MP) was used for the
      autofluorescence technique, and a Macular Metrics Densitometer (MM) was used for
      HFP. The mean MPOD values at 0.25 degrees  and 0.5 degrees  eccentricities using
      the Spectralis-MP were 0.51 +/- 0.12 and 0.48 +/- 0.13, respectively. In
      comparison, the MM based values were 0.72 +/- 0.23 and 0.61 +/- 0.25,
      respectively. High correlations between the Spectralis-MP and MM instrument were
      found (Pearson's correlation coefficients of 0.73 and 0.87 at 0.25 degrees  and
      0.5 degrees  eccentricities, respectively), but there was a systematic bias: the
      MPOD values by MM method were significantly higher than those by Spectralis-MP at
      0.25 degrees  eccentricity. High inter-examiner reproducibility and test-retest
      reliability were found for MM measurements at 0.5 degrees  eccentricity, but not
      at 0.25 degrees . The Spectralis-MP showed less inter-examiner and test-retest
      variability than the MM instrument at 0.25 degrees  and 0.5 degrees 
      eccentricities. We conclude that the Spectralis-MP, given its high agreement with
      the HFP method and due to its higher reproducibility and reliability, is well
      suited for clinical measurements of MPOD levels in Asian pigmented eyes.

PMID- 29357285
TI  - A model for investigating developmental eye repair in Xenopus laevis.
AB  - Vertebrate eye development is complex and requires early interactions between
      neuroectoderm and surface ectoderm during embryogenesis. In the African clawed
      frog, Xenopus laevis, individual eye tissues such as the retina and lens can
      undergo regeneration. However, it has been reported that removal of either the
      specified eye field at the neurula stage or the eye during tadpole stage does not
      induce replacement. Here we describe a model for investigating Xenopus
      developmental eye repair. We found that tailbud embryos can readily regrow eyes
      after surgical removal of over 83% of the specified eye and lens tissues. The
      regrown eye reached a comparable size to the contralateral control by 5 days and
      overall animal development was normal. It contained the expected complement of
      eye cell types (including the pigmented epithelium, retina and lens), and is
      connected to the brain. Our data also demonstrate that apoptosis, an early
      mechanism that regulates appendage regeneration, is also required for eye
      regrowth. Treatment with apoptosis inhibitors (M50054 or NS3694) blocked eye
      regrowth by inhibiting caspase activation. Together, our findings indicate that
      frog embryos can undergo successful eye repair after considerable tissue loss and
      reveals a required role for apoptosis in this process. Furthermore, this Xenopus
      model allows for rapid comparisons of productive eye repair and developmental
      pathways. It can also facilitate the molecular dissection of signaling mechanisms
      necessary for initiating repair.

PMID- 29357286
TI  - Reconstitution of RNA Polymerase I Upstream Activating Factor and the Roles of
      Histones H3 and H4 in Complex Assembly.
AB  - RNA polymerase I (Pol I) transcription in Saccharomyces cerevisiae requires four
      separate factors that recruit Pol I to the promoter to form a pre-initiation
      complex. Upstream Activating Factor (UAF) is one of two multi-subunit complexes
      that regulate pre-initiation complex formation by binding to the ribosomal DNA
      promoter and by stimulating recruitment of downstream Pol I factors. UAF is
      composed of Rrn9, Rrn5, Rrn10, Uaf30, and histones H3 and H4. We developed a
      recombinant Escherichia coli-based system to coexpress and purify
      transcriptionally active UAF complex and to investigate the importance of each
      subunit in complex formation. We found that no single subunit is required for UAF
      assembly, including histones H3 and H4. We also demonstrate that histone H3 is
      able to interact with each UAF-specific subunit, and show that there are at least
      two copies of histone H3 and one copy of H4 present in the complex. Together, our
      results provide a new model suggesting that UAF contains a hybrid H3-H4 tetramer
      like subcomplex.

PMID- 29357287
TI  - Interaction of KRas4B protein with C6-ceramide containing lipid model membranes.
AB  - Ras proteins are oncoproteins which play a pivotal role in cellular signaling
      pathways. All Ras proteins' signaling strongly depends on their correct
      localization in the cell membrane. Over 30% of cancers are driven by mutant Ras
      proteins, and KRas4B is the Ras isoform most frequently mutated. C6-ceramide has
      been shown to inhibit the growth activity of KRas4B mutated cells. However, the
      mechanism underlying this inhibition remains elusive. Here, we established a
      heterogeneous model biomembrane containing C6-ceramide. C6-ceramide incorporation
      does not disrupt the lipid membrane. Addition of KRas4B leads to drastic changes
      in the lateral membrane organization of the membrane, however. In contrast to the
      partitioning behavior in other membranes, KRas4B forms small, monodisperse
      nanoclusters dispersed in a fluid-like environment, in all likelihood induced by
      some kind of lipid sorting mechanism. Fluorescence cross-correlation data
      indicate no direct interaction between C6-ceramide and KRas4B, suggesting that
      KRas4B essentially recruits other lipids. A FRET-based binding assay reveals that
      the stability of KRas4B proteins inserted into the membrane containing C6
      ceramide is reduced. Based on the combined results obtained, we postulate a
      molecular mechanism for the inhibition of KRas4B mutated cells' activity through
      C6-ceramide.

PMID- 29357288
TI  - Microfluidic platforms for modeling biological barriers in the circulatory
      system.
AB  - Microfluidic platforms have recently become popular as in vitro models because of
      their superiority in recapitulating microenvironments compared with conventional
      in vitro models. By providing various biochemical and biomechanical cues, healthy
      and diseased models at the organ level can be applied to disease progression and
      treatment studies. Microfluidic technologies are especially suitable for modeling
      biological barriers because the flow in the microchannels mimics the blood flow
      and body fluids at the interfaces of crucial organs, such as lung, intestine,
      liver, kidney, brain, and skin. These barriers have similar structures and can be
      studied with similar approaches for the testing of pharmaceutical compounds.
      Here, we review recent developments in microfluidic platforms for modeling
      biological barriers in the circulatory system.

PMID- 29357289
TI  - pH-responsive nanoreservoirs based on hyaluronic acid end-capped mesoporous
      silica nanoparticles for targeted drug delivery.
AB  - Mesoporous silica nanoparticles (MSNs) are greatly appealing for efficient drug
      delivery due to their excellent drug loading capacities. However, it remains as a
      major challenge to realize site-specific controlled release with MSNs. This work
      examines a smart pH-responsive drug release system using MSNs for CD44-targeting
      drug delivery. Specifically, hyaluronic acid (HA) was applied as an end-capping
      agent to seal drug loads inside the mesoporous of MSNs through the acid labile
      hydrazine bonds. HA exposed on the surface of the particles can also serve as a
      targeting agent at the same time, enable site specific targeting toward CD-44
      overexpressing cells. The system showed a good stability at physiological pHs,
      yet drug release could be triggered in response to changes in pH. Further studies
      showed that the HA-fabricated particles could achieve much enhanced cellular
      uptake via CD44 receptor-mediated endocytosis by Hela cells (CD44 receptor
      positive), and as a result, doxorubicin-loaded MSNs exhibited significantly
      enhanced drug efficacy toward cancer cells overexpressing CD44 receptor (IC50 =
      0.56 MUg/mL), whereas the normal cells showed weakly cytotoxicity (IC50 = 1.03
      MUg/mL). Such a fabrication strategy may provide a new platform for preparation
      of high performance drug delivery systems for cancer therapy.

PMID- 29357290
TI  - Identification of hepatic thyroid hormone-responsive genes in neonatal rats:
      Potential targets for thyroid hormone-disrupting chemicals.
AB  - There have been many concerns about the possible adverse effects of thyroid
      hormone-disrupting chemicals in the environment. Because thyroid hormones are
      essential for regulating the growth and differentiation of many tissues,
      disruption of thyroid hormones during the neonatal period of an organism might
      lead to permanent effects on that organism. We postulated that there are target
      genes that are sensitive to thyroid hormones particularly during the neonatal
      period and that would thus be susceptible to thyroid hormone-disrupting
      chemicals. Global gene expression analysis was used to identify these genes in
      the liver of rat neonates. The changes in hepatic gene expression were examined
      24 h after administering 1.0, 10, and 100 ng/g body weight (bw) triiodothyronine
      (T3) to male rats on postnatal day 3. Thirteen upregulated and four downregulated
      genes were identified in the neonatal liver. Among these, Pdp2 and Slc25a25 were
      found to be upregulated and more sensitive to T3 than the others, whereas Cyp7b1
      and Hdc were found to be downregulated even at the lowest dose of 1.0 ng/g bw T3.
      Interestingly, when the responses of gene expression to T3 were examined in adult
      rats (8-week old), one-third of them did not respond to T3. The environmental
      chemicals with thyroid hormone-like activity, hydroxylated polybrominated
      diphenyl ethers, were then administered to neonatal rats to examine the effects
      on expression of the identified genes. The results showed that these chemicals
      were indeed capable of changing the expression of Slc25a25 and Hdc. Our results
      demonstrated a series of hepatic T3-responsive genes that are more sensitive to
      hormones during the neonatal period than during adulthood. These genes might be
      the potential targets of thyroid hormone-disrupting chemicals in newborns.

PMID- 29357291
TI  - Cholangiocytes in health and disease: From basic science to novel treatments.

PMID- 29357293
TI  - Mandibular advancement appliances for sleep-disordered breathing in children: A
      randomized crossover clinical trial.
AB  - OBJECTIVE: To test the short-term effectiveness of a mandibular advancement
      splint (MAS) for the management of sleep-disordered breathing (SDB) in children.
      METHODS: Eighteen SDB children were enrolled in a crossover randomized clinical
      trial and assigned to a treatment sequence starting either with an Active or a
      Sham MAS. Each appliance was worn for three weeks and treatment periods were
      separated by a two-week washout. Home-based polysomnographic data were collected
      before and after each treatment period. In addition, blood samples were collected
      at the end of each treatment period to assess serum levels of insulin-like growth
      factor-1 (IGF-1). The apnea-hypopnea index (AHI) and snoring time represented the
      main outcome variables. Secondary outcomes included IGF-1 levels, and
      questionnaire scores for quality of life and behavior. RESULTS: Compared to the
      Sham MAS, the wearing of the Active MAS resulted in a significant reduction in
      overall AHI (-37%; 95% CI = 15-53%; p = 0.002) and supine AHI (-4.1 events per
      hour; 95% CI = 1.8-6.4; p < 0.001). Mean snoring time per night was shorter with
      the Active MAS than with the Sham MAS (-46.3 min; 95% CI = 14.5-78.1; p = 0.004).
      Wearing of the Active MAS improved the ratings of quality of life and behavior (P
      <= 0.028), but there was no evidence that it influenced IGF-1 levels (P = 0.172).
      CONCLUSION: Wearing an Active MAS overnight, over a short period can be
      beneficial for SDB children, resulting in a clinically relevant reduction of
      supine AHI.

PMID- 29357294
TI  - Age effects on event-related potentials in individuals with amnestic Mild
      Cognitive Impairment during semantic categorization Go/NoGo tasks.
AB  - Both age and amnestic Mild Cognitive Impairment (aMCI), two major risk factors
      associated with Alzheimer's disease, have been associated with increased latency
      of event-related potentials, but how these factors interact has been less
      extensively evaluated. We examined the effects of age as a factor in 25
      individuals with aMCI and in 25 age-matched normal controls (NC) during semantic
      categorization Go/NoGo tasks. We found that N2 latency was prolonged with
      increasing age in aMCI but not in the NC, and P3 latency was prolonged with
      increasing age in both groups. Furthermore, aMCI individuals showed significant
      prolongation in N2 latency compared to NC in the older age group, whereas such
      group differences were not observed in the younger age group. Our findings
      suggest that N2 latency corresponding to cognitive control is susceptible to a
      combination of age and disease effects, especially in older individuals, and thus
      may be useful in differentiating normal from pathological aging in this age
      group.

PMID- 29357295
TI  - Association study of BDNF and DRD3 genes with alcohol use disorder in
      Schizophrenia.
AB  - Alcohol use disorder (AUD) is a leading risk factor of disease burden in the
      world. It is also commonly comorbid with over 20% of schizophrenia patients. The
      brain-derived neurotrophic factor (BDNF) and dopamine D3 receptor (DRD3) have
      been implicated in alcohol drinking behaviour. Previous genetic studies of the
      BDNF and DRD3 genes produced mixed findings; however, only one study investigated
      two BDNF genetic markers with alcohol dependence in schizophrenia patients. We
      investigated 15 single-nucleotide polymorphisms (SNPs) in DRD3 and four SNPs in
      BDNF for possible association with alcohol abuse or dependence in schizophrenia
      patients of European ancestry (N = 195). The patients were assessed for the
      occurrence of alcohol abuse or alcohol dependence using the Structured Clinical
      Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-I/P). We found the
      BDNF Val66Met to be associated with alcohol dependence (p = 0.004). We also found
      haplotypes across BDNF to be nominally associated with alcohol dependence.
      Analyses of DRD3 markers and haplotypes yielded mostly negative findings. Our
      findings support a role of the BDNF gene in alcohol dependence in schizophrenia
      patients. Larger samples are required to confirm our findings, particularly those
      of BDNF haplotypes.

PMID- 29357296
TI  - Spontaneous excision and facilitated recovery as a control for phenotypes arising
      from RNA interference and other dominant transgenes.
AB  - An essential control for genetic manipulation of microbes is the regeneration of
      the wild-type state and phenotype to validate that any mutant phenotypes are 'on
      target'. For Leishmania gene knockouts, this is often done by re-expression of
      the target gene from episomal vectors, often bearing counter-selectable markers.
      Methods for similarly validating the outcomes from dominant mutations such as
      those arising from RNA interference (RNAi) are needed. We present here such an
      approach, relying on facilitated recovery after spontaneous excision - or
      'popouts' - of dominant transgenes stably inserted into the ribosomal RNA array,
      utilizing GFP as a marker and single cell sorting to recover regenerated WT
      controls. We validate its utility using RNA interference knockdowns of the
      paraflagellar rod gene PFR2 of L. (Viannia) braziliensis. The method yields
      stably modified lines suitable for long term studies of Leishmania virulence,
      relies solely on host rather than introduced genetic machinery, and is thus
      readily applied in many species and circumstances including functional genetic
      testing.

PMID- 29357292
TI  - Reproducibility and replicability of rodent phenotyping in preclinical studies.
AB  - The scientific community is increasingly concerned with the proportion of
      published "discoveries" that are not replicated in subsequent studies. The field
      of rodent behavioral phenotyping was one of the first to raise this concern, and
      to relate it to other methodological issues: the complex interaction between
      genotype and environment; the definitions of behavioral constructs; and the use
      of laboratory mice and rats as model species for investigating human health and
      disease mechanisms. In January 2015, researchers from various disciplines
      gathered at Tel Aviv University to discuss these issues. The general consensus
      was that the issue is prevalent and of concern, and should be addressed at the
      statistical, methodological and policy levels, but is not so severe as to call
      into question the validity and the usefulness of model organisms as a whole. Well
      organized community efforts, coupled with improved data and metadata sharing,
      have a key role in identifying specific problems and promoting effective
      solutions. Replicability is closely related to validity, may affect
      generalizability and translation of findings, and has important ethical
      implications.

PMID- 29357297
TI  - Synergy evaluation of anti-Herpes Simplex Virus type 1 and 2 compounds acting on
      different steps of virus life cycle.
AB  - Despite the clinical need of novel and safe anti-herpetic compounds effective for
      treating both primary infections and reactivations of Herpes Simplex Virus type 1
      (HSV-1) and type 2 (HSV-2), the development of novel antivirals approved for
      clinical administration has been limited in the last decades to improvements of
      nucleoside analogues compounds. In this context, targeting different steps of the
      herpesvirus life cycle, including entry and cell-to-cell infection, can represent
      an important starting point for obtaining more efficient infection inhibition,
      and for overcoming both drug resistance and toxicity. Under these perspectives,
      testing possible synergy between drugs currently in clinical use and novel
      immunotherapeutics, such as neutralizing human monoclonal antibodies, represents
      a fascinating option. In the study here described we tested for the first-time
      possible combinations of inhibitors of Herpesvirus DNA synthesis and a human
      neutralizing IgG able to block also cell-to-cell infection, by analysing
      experimental results with different mathematical models. The present study
      clearly highlights the synergism between all anti-herpetic drugs tested in
      combination with the mAb; this strongly suggests possible reduction of anti
      herpetic drugs combined with the IgG for overcoming drug-related side effects, as
      indicated by Drug Reduction Index.

PMID- 29357298
TI  - Nonmetastatic Castration-resistant Prostate Cancer: A Modern Perspective.
AB  - Nonmetastatic castration-resistant prostate cancer (nmCRPC) presents a challenge
      to urologists as currently there are no Food and Drug Administration-approved
      therapies. However, there are new imaging modalities, including fluciclovine
      positron emission tomography-computed tomography and Ga-PSMA (prostate specific
      membrane antigent) positron emission tomography-computed tomography, which are
      improving accuracy of diagnosis. With improved imaging, we are better able to
      target therapy. Today there are 3 ongoing clinical trials studying second
      generation antiandrogens in nmCRPC, which hold the promise of a new treatment
      paradigm. In this article, we will review the new imaging techniques and the
      rationale behind novel treatment modalities in nmCRPC.

PMID- 29357299
TI  - Fusion genes: A promising tool combating against cancer.
AB  - The driving roles of fusion genes during tumorigenesis have been recognized for
      decades, with efficacies demonstrated in clinical diagnosis and targeted therapy.
      With advances in sequencing technologies and computational biology, a surge in
      the identification of fusion genes has been witnessed during the past decade. The
      discovery and presence of splicing based fusions in normal tissues have
      challenged our canonical conceptions on fusion genes and offered us novel medical
      opportunities. The specificity of fusion genes to neoplastic tissues and their
      diverse functionalities during carcinogenesis foster them as promising tools in
      the battle against cancer. It is time to re-visit and comb through our cutting
      edge knowledge on fusion genes to accelerate clinical translation of these
      internal markers. Urged as such, we are encouraged to categorize fusion events
      according to mechanisms leading to their generation, oncological consequences and
      clinical implications, offer insights on fusion occurrence across tumors from the
      system level, highlight feasible practices in fusion-related pharmaceutical
      development, and identify understudied yet important niches that may lead future
      research trend in this field.

PMID- 29357300
TI  - MICAN, a new fluorophore for vital and non-vital staining of human cells.
AB  - Fluorescence time-lapse microscopy is in connection with the invasive properties
      of fluorochrome applied, and with the toxicity of the excitation energy and
      wavelength of the dye itself. Experiments with the newly synthesized fluorescent
      dye 1-N-methylamino-5-isocyanonaphthalene (MICAN) served to test its cytotoxicity
      on human HaCaT keratinocyte cell cultures. Experiments related to staining
      capability were performed with paraformaldehyde (PFA) fixed cells and observed
      with fluorescence microscope. It was assumed that the fluorophore 1-amino-5
      isocyanonaphthalene (ICAN) and especially its N-methylamino derivative MICAN,
      containing condensed aromatic rings could serve as a nonselective fluorescent dye
      capable to stain cellular structures of fixed, living, damaged and dead cells.
      This notion was confirmed by the MICAN staining of cytoplasmic proteins primarily
      rough endoplasmic reticulum (RER), smooth endoplasmic reticulum (SEM) and less
      efficiently nuclear proteins suggesting the involvement of staining of
      subcellular structures involved in protein synthesis. MICAN was not only well
      tolerated by living cells but turned out to be a strong heterochromatin and RER
      staining agent. This led to the development of a MICAN staining protocol for
      native and living samples. Relative to other fluorescent dyes, MICAN is not only
      useful but also cost-effective. Toxicology tests were performed using 30, 10, 5,
      0.5 MUg/ml MICAN concentrations. Time-lapse videomicroscopy at near-infrared
      (NIR) illumination has been used for the examination of MICAN effect on cell
      division. It was found that MICAN as a vital stain had no significant harmful
      effect on HaCaT cells. MICAN turned out to be a non-toxic, highly quantum
      efficient vital stain with minimal, or no photobleaching, and can be applied to
      co-stain with propidium-iodide due the strong spectral separation.

PMID- 29357301
TI  - Delivery of cellular factors to regulate bone healing.
AB  - Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate
      and complex interplay of cellular and molecular processes, which tightly involve
      the immune system. Pathological settings of anatomical, biomechanical or
      inflammatory nature may lead to impaired bone healing. Innovative strategies to
      enhance bone repair, including the delivery of osteoprogenitor cells or of potent
      cytokines/morphogens, indicate the potential of 'orthobiologics', but are not
      fully satisfactory. Here, we review different approaches based on the delivery of
      regenerative cues produced by cells but in cell-free, possibly off-the-shelf
      configurations. Such strategies exploit the paracrine effect of the secretome of
      mesenchymal stem/stromal cells, presented in soluble form, shuttled through
      extracellular vesicles, or embedded within the network of extracellular matrix
      molecules. In addition to osteoinductive molecules, attention is given to factors
      targeting the resident immune cells, to reshape inflammatory and immunity
      processes from scarring to regenerative patterns.

PMID- 29357303
TI  - Single-step genomic evaluation improves accuracy of breeding value predictions
      for resistance to infectious pancreatic necrosis virus in rainbow trout.
AB  - The aim of this study was to compare the accuracy of breeding values (EBVs)
      predicted using the traditional pedigree based Best Linear Unbiased Prediction
      (PBLUP) and the single-step genomic Best Linear Unbiased Prediction (ssGBLUP) for
      resistance against infectious pancreatic necrosis virus (IPNV) in rainbow trout.
      A total of 2278 animals were challenged against IPNV and 768 individuals were
      genotyped using a 57 K single nucleotide polymorphism array for rainbow trout.
      Accuracies for both methods were assessed using five-fold cross-validation. The
      heritabilities were higher for PBLUP compared to ssGBLUP. The ssGBLUP accuracies
      outperformed PBLUP in 7 and 11% for days to death and binary survival,
      respectively. The ssGBLUP could be an alternative approach to improve the
      accuracy of breeding values for resistance against infectious pancreatic necrosis
      virus in rainbow trout, using information from genotyped and non-genotyped
      animals.

PMID- 29357302
TI  - Role of the inositol pyrophosphate multikinase Kcs1 in Cryptococcus inositol
      metabolism.
AB  - Cryptococcus neoformans is the most common cause of deadly fungal meningitis.
      This fungus has a complex inositol acquisition and utilization system, and our
      previous studies have shown the importance of inositol utilization in
      cryptococcal development and virulence. However, how inositol utilization is
      regulated in this fungus remains unknown. In this study, we found that inositol,
      irrespective of the presence of glucose in the media, represses the expression of
      C. neoformans genes involved in inositol pyrophosphate biosynthesis, including
      the gene encoding inositol hexakisphosphate kinase Kcs1. Kcs1 was recently
      reported to regulate inositol metabolism in Saccharomyces cerevisiae and to
      impact virulence in C. neoformans. To examine the potential role of Kcs1 in
      inositol regulation in C. neoformans, we generated the kcs1Delta mutant and
      compared its phenotype with the wild type strain. We found that Kcs1 negatively
      regulates inositol uptake and catabolism in C. neoformans, but, in contrast to
      Kcs1 function in S. cerevisiae, does not appear to regulate inositol
      biosynthesis. Together, these results show that Kcs1 functions to fine-tune
      inositol acquisition to maintain inositol homeostasis in C. neoformans.

PMID- 29357304
TI  - Infection with anthroponotic Cryptosporidium parvum does not fully protect the
      host against a subsequent challenge with C. hominis.
AB  - Cryptosporidium hominis and Cryptosporidium parvum are the major Cryptosporidium
      species that infect humans. Earlier studies in gnotobiotic piglets, model
      susceptible to both, showed that piglets recovered from infection with C. hominis
      were fully protected against challenge with same species but incompletely
      protected against C. parvum challenge. In the present study, piglets were
      infected with C. parvum first, and after recovery were re-challenged with C.
      parvum or C. hominis. Again, full protection was only observed when piglets were
      challenged with the homologous parasite strain. Although the two species are
      genetically/antigenically almost identical, they do not confer complete
      protection against each other.

PMID- 29357305
TI  - Carotid intima-media thickness and anti-hypertensive treatment: Focus on
      angiotensin II receptor blockers.
AB  - Carotid intima-media thickness (CIMT), as assessed by ultrasonography, has been
      shown to be directly related to cardiovascular (CV) morbidity and mortality
      independently of conventional risk factors. Thus, CIMT has been proposed as a
      marker of CV risk and a surrogate end-point for therapeutic interventions. In the
      present article we will review available literature about CIMT
      clinical/prognostic significance in order to offer an updated comprehensive
      information on this topic. In particular, the anti-atherosclerotic effect of
      angiotensin II receptor blockers (ARBs) in the hypertensive setting will be
      addressed, based on findings provided by double blind, randomized, prospective
      studies comparing CIMT longitudinal changes. Our review, including 8 studies
      totaling 1154 hypertensive participants, shows that ARBs are as effective as the
      other classes of antihypertensive drugs in preventing/regressing subclinical
      carotid damage and that findings supporting their superiority in this field are
      limited and not univocal. Future studies aimed to clarify the therapeutic impact
      of ARBs on CIMT changes and their prognostic implications are warranted.

PMID- 29357306
TI  - Intermittent intense exercise protects against cognitive decline in a similar
      manner to moderate exercise in chronically stressed mice.
AB  - It is well known that regular low or mild exercise helps to improve and maintain
      cognition. On the other hand, ever thought many people prefer high-intensity
      exercise (e.g., running, swimming, biking, soccer, basketball, etc.) to get rid
      of stress or improve their health, the previous studies reported that intense
      exercise either impairs cognition or has no effect on cognitive function.
      However, we previously showed that intermittent intense exercise prevents stress
      induced depressive behavior in mice in a similar manner to moderate exercise. On
      the basis of this finding, we investigated the effect of intermittent intense
      exercise on cognitive deficit in chronically stressed mice. A total of forty mice
      were evenly divided into control, stressed, stressed with moderate exercise, and
      stressed with intense exercise groups. The stressed mice were chronically exposed
      a restraint stress (10 h/day, 6 days/week for 7 weeks). The exercised mice were
      subjected to intermittent intense or endurance moderate running on the treadmill
      three times a week. Cognition was evaluated using the Morris water maze test and
      the object recognition test. Chronic stress decreased cognition, and newborn cell
      survival and blood vessel density in the hippocampus. However, both regular
      intense and moderate exercise prevented decrease of cognition, improved newborn
      cell survival and blood vessel density. These findings suggest that intermittent
      intense exercise may protect against decrease of cognition in a similar manner to
      moderate exercise and that both exercise-induced protection of decrease of
      cognition is closely related to newborn cell survival and angiogenesis in the
      hippocampus.

PMID- 29357307
TI  - Epigenetics, microbiota, and intraocular inflammation: New paradigms of immune
      regulation in the eye.
AB  - Sight threatening immune responses that damage the eye characterize intraocular
      inflammatory diseases. These diseases including uveitis and age-related macular
      degeneration are worryingly common and quality of life shattering. Genetic
      studies in past decades significantly advanced our understanding of the etiology
      of these devastating diseases. Unfortunately, patient genetics alone failed to
      adequately explain disease origin, susceptibility, and progression. Non-genetic
      factors such as the epigenetic regulation of ocular diseases and the
      environmental factors triggering intraocular inflammation offer new insight into
      intraocular inflammatory disorders. Importantly, mounting evidence is signaling
      that dysbiosis of human microbiota leads to rapid epigenomic reprograming of host
      cells and results in the onset of many diseases. In this review, we discuss how
      epigenetic mechanisms and microbiota may cooperate to initiate and perpetuate
      ocular inflammation. Lastly, we propose that the discovery of intraocular
      microbiota presents a significant shift in thought affecting current approaches
      to the diagnosis, treatment, and prevention of intraocular inflammatory diseases
      such as uveitis and age-related macular degeneration. The geographical and
      genetic background difference in both disease presentation and genetic
      association of intraocular inflammatory diseases may be due to the variation of
      intraocular microbiota.

PMID- 29357309
TI  - Simple Improvisation to Enhance Utility of Fluorescein Sodium in Resection of
      Intracranial Lesions at Routine Neurosurgical Centers.
AB  - INTRODUCTION: Fluorescein sodium is one of the fluorophores that is used in the
      resection of intracranial lesions. It is commonly used along with a customized
      microscope, which is expensive and not available universally. In this study, we
      describe a simple, inexpensive method for better visualization of intracranial
      and spinal cord lesions with fluorescein. MATERIALS AND METHODS: After a test
      dose, 20 mg/kg of fluorescein sodium was administered intravenously at the time
      of intubation. A blue light source was used before resection for precise
      localization of the intracranial lesions after durotomy. Most of the resection
      was done under the white light, while the blue light was used intermittently to
      delineate the pathologic tissue from the normal tissue and to ensure safe maximal
      resection. The intensity of fluorescein staining under white light and blue light
      was noted. RESULTS: The study comprised 40 cases of gliomas, meningiomas,
      abscesses, spinal cord tumors, and cerebellopontine angle lesions. Thirty-five
      lesions showed good fluorescence under the blue light, which helped us achieve
      better resection of the pathologic lesions. CONCLUSIONS: Fluorescein sodium is a
      safe dye; it can be used to aid in precise localization and safe maximal
      resection of the pathologic tissue with the help of a blue light source at any
      center with challenged resources. The blue light enhances the fluorescence and
      visualization of the pathologic tissue, and this technique can be adopted by any
      surgeon without much difficulty even with a basic neurosurgical setup.

PMID- 29357310
TI  - Early Childhood Stress and Child Age Predict Longitudinal Increases in Obesogenic
      Eating Among Low-Income Children.
AB  - OBJECTIVE: To identify whether psychosocial stress exposure during early
      childhood predicts subsequent increased eating in the absence of hunger (EAH),
      emotional overeating, food responsiveness, and enjoyment of food. METHODS: This
      was an observational longitudinal study. Among 207 low-income children (54.6% non
      Hispanic white, 46.9% girls), early childhood stress exposure was measured by
      parent report and a stress exposure index calculated, with higher scores
      indicating more stress exposure. Eating behaviors were measured in early (mean,
      4.3; standard deviation, 0.5 years) and middle (mean, 7.9; standard deviation,
      0.7 years) childhood. Observed EAH was assessed by measuring kilocalories of
      palatable food the child consumed after a meal. Parents reported on child eating
      behaviors on the Child Eating Behavior Questionnaire. Child weight and height
      were measured and body mass index z score (BMIz) calculated. Multivariable linear
      regression, adjusting for child sex, race/ethnicity, and BMIz, was used to
      examine the association of stress exposure with rate of change per year in each
      child eating behavior. RESULTS: Early childhood stress exposure predicted yearly
      increases in EAH (beta = 0.14; 95% confidence interval, 0.002, 0.27) and
      Emotional Overeating (beta = 0.14; 95% confidence interval, 0.008, 0.27). Stress
      exposure was not associated with Food Responsiveness (trend for decreased
      Enjoyment of Food; beta = -0.13; 95% confidence interval, 0.002, -0.26). All
      child obesogenic eating behaviors increased with age (P < .05). CONCLUSIONS:
      Early stress exposure predicted increases in child eating behaviors known to
      associate with overweight/obesity. Psychosocial stress may confer
      overweight/obesity risk through eating behavior pathways. Targeting eating
      behaviors may be an important prevention strategy for children exposed to stress.

PMID- 29357311
TI  - d-Amino acids in molecular evolution in space - Absolute asymmetric photolysis
      and synthesis of amino acids by circularly polarized light.
AB  - Living organisms on the Earth almost exclusively use l-amino acids for the
      molecular architecture of proteins. The biological occurrence of d-amino acids is
      rare, although their functions in various organisms are being gradually
      understood. A possible explanation for the origin of biomolecular homochirality
      is the delivery of enantioenriched molecules via extraterrestrial bodies, such as
      asteroids and comets on early Earth. For the asymmetric formation of amino acids
      and their precursor molecules in interstellar environments, the interaction with
      circularly polarized photons is considered to have played a potential role in
      causing chiral asymmetry. In this review, we summarize recent progress in the
      investigation of chirality transfer from chiral photons to amino acids involving
      the two major processes of asymmetric photolysis and asymmetric synthesis. We
      will discuss analytical data on cometary and meteoritic amino acids and their
      potential impact delivery to the early Earth. The ongoing and future ambitious
      space missions, Hayabusa2, OSIRIS-REx, ExoMars 2020, and MMX, are scheduled to
      provide new insights into the chirality of extraterrestrial organic molecules and
      their potential relation to the terrestrial homochirality. This article is part
      of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr.
      Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.

PMID- 29357308
TI  - Systemic inflammation as a predictor of brain aging: Contributions of physical
      activity, metabolic risk, and genetic risk.
AB  - Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and
      age-related brain degeneration. Metabolic and genetic risk factors, and physical
      activity may, in turn, influence these inflammatory processes. Some of these risk
      factors are modifiable, and interact with each other. Understanding how these
      processes together relate to brain aging will help to inform future interventions
      to treat or prevent cognitive decline. We used brain magnetic resonance imaging
      (MRI) to scan 335 older adult humans (mean age 77.3 +/- 3.4 years) who remained
      non-demented for the duration of the 9-year longitudinal study. We used
      structural equation modeling (SEM) in a subset of 226 adults to evaluate whether
      measures of baseline peripheral inflammation (serum C-reactive protein levels;
      CRP), mediated the baseline contributions of genetic and metabolic risk, and
      physical activity, to regional cortical thickness in AD-relevant brain regions at
      study year 9. We found that both baseline metabolic risk and AD risk variant
      apolipoprotein E epsilon4 (APOE4), modulated baseline serum CRP. Higher baseline
      CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an
      effect between higher metabolic risk and thinner cortex in those regions. A
      higher polygenic risk score composed of variants in immune-associated AD risk
      genes (other than APOE) was associated with thinner regional cortex. However, CRP
      levels did not mediate this effect, suggesting that other mechanisms may be
      responsible for the elevated AD risk. We found interactions between genetic and
      environmental factors and structural brain health. Our findings support the role
      of metabolic risk and peripheral inflammation in age-related brain decline.

PMID- 29357312
TI  - Pressure algometry is an excellent tool to measure knee pain relief after a
      closing-wedge high tibial osteotomy.
AB  - PURPOSE: The aim of this study was to assess the utility of pressure algometry
      (PA) to measure pain relief in the medial part of the knee after a closing-wedge
      high tibial osteotomy (CWHTO). METHODS: Prospective study including 44 CWHTO.
      Pain relief was evaluated with the visual analogue scale (VAS) and PA, a
      radiological study was done and a functional assessment was carried out with the
      KSS preoperatively, at 6-months and at 1-year after the surgery. PA was applied
      to the medial and lateral part of the knee and to the infra-clavicular fossa as a
      control point. RESULTS: The mechanical femorotibial angle was changed from 172.2
      degrees  (SD2.2) to 180.6 degrees  (SD2.6) (p=0.00). KSS Knee improved from 53.4
      (SD11.2) to 92.8 (SD7.3) (p=0.00), KSS Function from 69.4 (SD9.3) to 93.1 (SD8)
      (p=0.00). The VAS went from 6.84 (SD1.5) to 2.5 (SD2.1) (p=0.00) at the 1-year
      follow-up. The pressure pain threshold (PPT), measured with PA in the medial part
      of the knee also improved from 348.8kPa (SD159.3) to 447.1kPa (SD218.8) (p=0.01).
      However, the PPT in the lateral part of the knee and in the sub-clavicular fossa
      remained the same from the preoperative period to 6-months and 1-year,
      postoperatively. Neither were there any differences between the 6-month and 1
      year postoperative values in terms of the different functional, radiological and
      pain relief obtained. CONCLUSION: The pain relief obtained after a CWHTO in the
      medial part of the knee can be measured by using PA. Furthermore, the functional
      and pain improvement obtained at 1-year follow-up is no better than those
      obtained at 6-months postoperatively.

PMID- 29357313
TI  - Addressing people and place microenvironments in weight loss disparities (APP
      Me): Design of a randomized controlled trial testing timely messages for weight
      loss behavior in low income Black and White Women.
AB  - BACKGROUND: Behavioral interventions for weight loss have been less effective in
      lower income and black women. These poorer outcomes may in part be related to
      these women having more frequent exposures to social and physical situations that
      are obesogenic, i.e., eating and sedentary cues or situations. OBJECTIVES:
      Working with obese, lower income Black and White Women, Addressing People and
      Place Microenvironments (APP-Me) was designed to create awareness of self
      behavior at times and places of frequent eating and sedentary behavior. DESIGN:
      APP-Me is being evaluated in a randomized controlled trial with 240 participants
      recruited from federally qualified health centers located in a single Midwestern
      city. All participants complete four weeks of ecological momentary assessments
      (EMA) of situations and behavior. At the end of the four weeks, participants are
      randomized to enhanced usual care (UC) or UC plus APP-Me. METHODS: APP-Me is an
      automated short messaging system (SMS). Messages are text, image, audio, or a
      combination, and are delivered to participants' mobile devices with the intent of
      creating awareness at the times and places of frequent eating or sedentary
      behavior. The EMA data inform the timing of message deliveries. SUMMARY: This
      project aims to create and test timely awareness messages in a subpopulation that
      has not responded well to traditional behavioral interventions for weight loss.
      Novel aspects of the study include the involvement of a low income population,
      the use of data on time and place of obesogenic behavior, and message delivery
      time tailored to an individual's behavioral patterns.

PMID- 29357314
TI  - The effects of estrogen deficiency on cortical bone microporosity and
      mineralization.
AB  - Recent studies have demonstrated matrix-mineral alterations in bone tissue
      surrounding osteocytes in estrogen-deficient animals. While cortical bone
      porosity has been shown to be a contributor to the mechanical properties of bone
      tissue, little analysis has been done to investigate the effects of estrogen
      deficiency on bone's microporosities, including the vascular and osteocyte
      lacunar porosities. In this study we examined alterations in cortical bone
      microporosity, mineralization, and cancellous bone architecture due to estrogen
      deficiency in the ovariectomized rat model of postmenopausal osteoporosis. Twenty
      week-old female Sprague-Dawley rats were subjected to either ovariectomy or sham
      surgery. Six weeks post-surgery tibiae were analyzed using high-resolution micro
      CT, backscattered electron imaging, nanoindentation, and dynamic
      histomorphometry. Estrogen deficiency caused an increase in cortical bone
      vascular porosity, with enlarged vascular pores and little change in tissue
      mineral density in the proximal tibial metaphysis. Measurements of cancellous
      architecture corresponded to previous studies reporting a decrease in bone volume
      fraction, an increase in trabecular separation, and a decrease in trabecular
      number in the proximal tibia due to estrogen deficiency. Nanoindentation results
      showed no differences in matrix stiffness in osteocyte-rich areas of the proximal
      tibia of estrogen-deficient rats, and bone labeling and backscattered electron
      imaging showed no significant changes in mineralization around the vascular
      pores. The findings demonstrate local surface alterations of vascular pores due
      to estrogen deficiency. An increase in cortical vascular porosity may diminish
      bone strength as well as alter bone mechanotransduction via interstitial fluid
      flow, both of which could contribute to bone fragility during postmenopausal
      osteoporosis.

PMID- 29357315
TI  - Different impact of prism adaptation rehabilitation in spatial neglect and
      anosognosia for hemiplegia.

PMID- 29357317
TI  - Recurrence in Deep Infiltrating Endometriosis: A Systematic Review of the
      Literature.
AB  - Deep infiltrative endometriosis (DIE) is an enigmatic disease that typically
      impacts the rectovaginal septum, uterosacral ligaments, pararectal space, and
      vesicouterine fold but can involve the rectum, sigma, ileum, ureters, diaphragm,
      and other less common sites. Surgery is the treatment of choice because medical
      management alone commonly fails in controlling the symptoms although recurrence
      is very high after surgical treatment. The goal of the current study was to
      review recurrence rates and identify risk factors related to recurrence after
      surgery for DIE. The review involved searching the Cochrane Library, PubMed, and
      Google Scholar for relevant articles in accordance with the study's inclusion
      criteria; 45 studies were considered suitable. The results showed a wide
      heterogeneity regarding DIE recurrence because of inconsistent recurrence
      definitions and follow-up length. Younger age and high body mass index were found
      to be risk factors for DIE recurrence. Lack of complete surgical excision was
      another independent risk factor for recurrence of disease. In conclusion, there
      is a need for prospective studies and a more homogeneous standard for surgical
      treatment of DIE.

PMID- 29357316
TI  - A novel mode for transcription inhibition mediated by PNA-induced R-loops with a
      model in vitro system.
AB  - The selective inhibition of transcription of a chosen gene by an artificial agent
      has numerous applications. Usually, these agents are designed to bind a specific
      nucleotide sequence in the promoter or within the transcribed region of the
      chosen gene. However, since optimal binding sites might not exist within the
      gene, it is of interest to explore the possibility of transcription inhibition
      when the agent is designed to bind at other locations. One of these possibilities
      arises when an additional transcription initiation site (e.g. secondary promoter)
      is present upstream from the primary promoter of the target gene. In this case,
      transcription inhibition might be achieved by inducing the formation of an RNA
      DNA hybrid (R-loop) upon transcription from the secondary promoter. The R-loop
      could extend into the region of the primary promoter, to interfere with promoter
      recognition by RNA polymerase and thereby inhibit transcription. As a sequence
      specific R-loop-inducing agent, a peptide nucleic acid (PNA) could be designed to
      facilitate R-loop formation by sequestering the non-template DNA strand. To
      investigate this mode for transcription inhibition, we have employed a model
      system in which a PNA binding site is localized between the T3 and T7 phage RNA
      polymerase promoters, which respectively assume the roles of primary and
      secondary promoters. In accord with our model, we have demonstrated that with PNA
      bound DNA substrates, transcription from the T7 promoter reduces transcription
      from the T3 promoter by 30-fold, while in the absence of PNA binding there is no
      significant effect of T7 transcription upon T3 transcription.

PMID- 29357318
TI  - Ayahuasca: A risk for travellers?

PMID- 29357319
TI  - Microbial nanowires - Electron transport and the role of synthetic analogues.
AB  - : Electron transfer is central to cellular life, from photosynthesis to
      respiration. In the case of anaerobic respiration, some microbes have
      extracellular appendages that can be utilised to transport electrons over great
      distances. Two model organisms heavily studied in this arena are Shewanella
      oneidensis and Geobacter sulfurreducens. There is some debate over how, in
      particular, the Geobacter sulfurreducens nanowires (formed from pilin
      nanofilaments) are capable of achieving the impressive feats of natural
      conductivity that they display. In this article, we outline the mechanisms of
      electron transfer through delocalised electron transport, quantum tunnelling, and
      hopping as they pertain to biomaterials. These are described along with existing
      examples of the different types of conductivity observed in natural systems such
      as DNA and proteins in order to provide context for understanding the
      complexities involved in studying the electron transport properties of these
      unique nanowires. We then introduce some synthetic analogues, made using
      peptides, which may assist in resolving this debate. Microbial nanowires and the
      synthetic analogues thereof are of particular interest, not just for
      biogeochemistry, but also for the exciting potential bioelectronic and clinical
      applications as covered in the final section of the review. STATEMENT OF
      SIGNIFICANCE: Some microbes have extracellular appendages that transport
      electrons over vast distances in order to respire, such as the dissimilatory
      metal-reducing bacteria Geobacter sulfurreducens. There is significant debate
      over how G. sulfurreducens nanowires are capable of achieving the impressive
      feats of natural conductivity that they display: This mechanism is a fundamental
      scientific challenge, with important environmental and technological
      implications. Through outlining the techniques and outcomes of investigations
      into the mechanisms of such protein-based nanofibrils, we provide a platform for
      the general study of the electronic properties of biomaterials. The implications
      are broad-reaching, with fundamental investigations into electron transfer
      processes in natural and biomimetic materials underway. From these studies,
      applications in the medical, energy, and IT industries can be developed utilising
      bioelectronics.

PMID- 29357320
TI  - Ginsenoside Rb1 Protects the Brain from Damage Induced by Epileptic Seizure via
      Nrf2/ARE Signaling.
AB  - BACKGROUND/AIMS: Ginsenoside Rb1 (Rb1) has been reported to have varieties of
      neuroprotective effects. This study aimed to evaluate the effects of Rb1 on
      pentylenetetrazol (PTZ)-induced rat brain injury and Mg2+ free-induced neuron
      injury and analyzed the detailed molecular mechanisms in vivo and in vitro.
      METHODS: Seizure duration and latency were measured in epilepsy kindled rat. The
      cognitive impairment was assessed by Morris water maze (MWM) test. Oxidative
      stress parameters, malondialdehyde (MDA) and glutathione (GSH) were measured by
      the 2-thiobarbituric acid methods and the DTNB-GSSG reductase recycling methods.
      Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining.
      Neuronal apoptosis was measured by Annexin V-FITC and propidium iodide (PI)
      staining. Immunohistochemistry and immunofluorescence staining were performed to
      evaluate Nrf2 and HO-1 expressions. Expression of Nrf2, HO-1, Bcl-2, iNOS and LC3
      were evaluated by western blot. RESULTS: The PTZ-injured rats presented longer
      seizure duration and shorter seizure latency. Rb1 ameliorated these effects, as
      well as the cognitive deficits caused by PTZ exposure. Besides, Rb1 dose
      dependently increased GSH levels, decreased MDA levels and alleviated neuronal
      damage in PTZ-treated rats. In vitro, Rb1 increased cell viability and decreased
      neuronal apoptosis in a dose-dependent manner under Mg2+ free condition.
      Moreover, in vivo and in vitro, Rb1 enhanced both the Nrf2 and HO-1 expressions.
      Furthermore, upregulation of the expression of Bcl-2 and downregulation of the
      expression of iNOS and LC3 were observed. However, knockdown of Nrf2 adversely
      affected the protective effects of Rb1 in epileptic hippocampal neurons.
      CONCLUSION: Rb1 conferred neuroprotective effects against PTZ-induced brain
      damage and Mg2+ free-induced neuron injury by activating Nrf2/ARE signaling.

PMID- 29357321
TI  - B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts
      Poor Prognosis of Early-Stage Colorectal Cancer.
AB  - BACKGROUND/AIMS: It is well established that many non-trophoblastic tumors
      secrete HCG (human chorionic gonadotropin) and that such secretion is correlated
      with the poor prognosis of tumor patients. This study aims to analyze the
      correlation between beta-HCG expression and outcome of colorectal cancer (CRC)
      and understand its role in CRC pathology Methods: We detected the mRNA and
      protein expression of beta-HCG in human CRC tissues with RT-qPCR and
      immunohistochemistry, and we compared the clinical-pathological characteristics,
      prognosis and progression between the beta-HCG positive and negative groups. We
      also generated CRC cell lines with beta-HCG over-expression as well as beta-HCG
      stable knockout, and evaluated cell function and mechanism in vitro and in vivo.
      RESULTS: Fifty out of 136 CRC patients (37%) expressed beta-HCG at the invasive
      front. Clinical-pathological data showed that beta-HCG was positively correlated
      with Dukes staging (P=0.031) and lymph node metastasis (P=0.012). Survival
      analysis suggested that the patients with high expression of beta-HCG had poorer
      prognosis than those with low beta-HCG expression (P=0.0289). beta-HCG expression
      level was also positively correlated with tumor invasion in early-stage CRC
      patient tissues (P=0.0227). Additionally beta-HCG promoted the migration and
      invasion of CRC in vitro and in vivo but had no effect on the proliferation of
      tumor cells. CONCLUSION: Our study demonstrated that beta-HCG was ectopically
      expressed in the CRC patients and its high expression correlated with poor
      prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes
      the migration and invasion of CRC by epithelial-mesenchymal transition (EMT).

PMID- 29357322
TI  - Hypoxia Suppresses TGF-B1-Induced Cardiac Myocyte Myofibroblast Transformation by
      Inhibiting Smad2/3 and Rhoa Signaling Pathways.
AB  - BACKGROUND/AIMS: Hypoxia modulation of transforming growth factor (TGF)- beta
      induced signaling during myofibroblast transformation is dependent on the
      specific cell type. The purpose of this study was to explore the effects of
      hypoxia on myofibroblast transformation of TGF-beta1-induced cardiomyocyte H9c2
      cells. METHODS: H9c2 cells were cultured for intermittent hypoxia treatment and
      TGF-beta1 treatment. alpha-Smooth muscle actin (alpha-SMA) expression was
      examined by western blotting and immunofluorescence after treatment. To further
      explore the possible mechanism for this effect, the effects of hypoxia on three
      early TGF-beta-dependent signaling pathways, i.e. the Smad2/3, RhoA and mitogen
      activated protein kinase (MAPK) pathways, were screened by western blotting.
      RESULTS: Intermittent hypoxia induced TGF-beta1 expression, but had no effect on
      alpha-SMA expression. Exogenous TGF-beta1 alone upregulated alpha-SMA expression
      in H9c2 cells in a concentration- and time-dependent manner. alpha-SMA expression
      declined with the duration of hypoxia after intermittent hypoxia and exogenous
      TGF-beta1 co-treatment. Phospho-JNK and phospho-p38 levels were not significantly
      altered after TGF-beta1 and hypoxia treatment. However, levels of phospho-ERK
      increased after TGF-beta1 treatment and continued to increase after hypoxia co
      treatment. The activation of phospho-Smad2/3 and phospho-RhoA induced by TGFbeta1
      was significantly reduced after hypoxia co-treatment. CONCLUSION: Hypoxia can
      inhibit TGF-beta1-induced H9c2 myofibroblast transformation, based on inhibition
      of alpha-SMA expression by suppressing signaling downstream of TGF-beta1, Smad2/3
      and RhoA. It suggested that TGF-beta-mediated cardiomyocyte transformation is not
      involved in hypoxia-mediated fibrosis.

PMID- 29357323
TI  - Plumbagin Triggers ER Stress-Mediated Apoptosis in Prostate Cancer Cells via
      Induction of ROS.
AB  - BACKGROUND/AIMS: Prostate cancer (PCa) is the second most frequently diagnosed
      cancer in men worldwide. Currently available therapies for hormone-refractory PCa
      are only marginally effective. Plumbagin (PLB), a natural naphthoquinone isolated
      from the traditional folk medicine Plumbago zeylanica, is known to selectively
      kill tumor cells. Nevertheless, antitumor mechanisms initiated by PLB in cancer
      cells have not been fully defined. METHODS: MTT assay was used to evaluate the
      effect of PLB on the viability of cancer cells. Cell apoptosis and reactive
      oxygen species (ROS) production were determined by flow cytometry. Protein
      expression was detected by western blotting. In vivo anti-tumor effect was
      measured by using tumor xenoqraft model in nude mice. RESULTS: In the present
      study, we found that PLB decreases cancer cell growth and induces apoptosis in
      DU145 and PC-3 cells. In addition, by increasing intracellular ROS levels, PLB
      induced a lethal endoplasmic reticulum stress response in PCa cells. Importantly,
      blockage of ROS production significantly reversed PLB-induced ER stress
      activation and cell apoptosis. In vivo, we found that PLB inhibits the growth of
      PCa xenografts without exhibiting toxicity Treatment of mice bearing human PCa
      xenografts with PLB was also associated with induction of ER stress activation.
      CONCLUSION: Inducing ER stress by PLB thus discloses a previously unrecognized
      mechanism underlying the biological activity of PLB and provides an in-depth
      insight into the action of PLB in the treatment of hormone-refractory PCa.

PMID- 29357325
TI  - Buprenorphine Formulations: Clinical Best Practice Strategies Recommendations for
      Perioperative Management of Patients Undergoing Surgical or Interventional Pain
      Procedures.
AB  - BACKGROUND: Starting with approval for clinical use in the treatment of opioid
      dependence in October 2002 by the Food and Drug Administration (FDA),
      buprenorphine has become an integral treatment option and in recent years, in
      chronic pain management. Buprenorphine possesses a unique pharmacodynamic and
      pharmacokinetic profile that can potentially make perioperative analgesia
      challenging. OBJECTIVES: To date no unified guidelines or recommendations are
      available for buprenorphine product management during the perioperative period.
      The present investigation aims to review the literature and provide
      recommendations when encountering a patient on buprenorphine therapy who is
      scheduled for a surgical or interventional pain procedure. METHODS: Clinical
      studies and reviews were searched using the PubMed National Center for
      Biotechnology Information database using MeSH terms buprenorphine, buprenorphine
      and naloxone, suboxone, perioperative, and postoperative pain. RESULTS: PubMed
      National Center for Biotechnology Information database search resulted in one
      randomized control trial, one prospective case matched cohort, one retrospective
      cohort, 0 case series, 4 case reports, and 6 review articles. Key literature is
      reviewed and summarized. LIMITATIONS: Only 12 articles were included, which
      permits only limited recommendations drawn from this review. CONCLUSIONS: The
      perioperative management of buprenorphine and buprenorphine/naloxone are
      dependent on several key factors. The nature of the surgery, namely the
      postoperative opioid requirement, elective versus emergency surgery, patient
      characteristics, formulation of buprenorphine, and indication for buprenorphine
      or buprenorphine/naloxone therapy must be considered when devising a plan.
      Several options exist when formulating a plan for the perioperative management,
      including continuing buprenorphine therapy or holding buprenorphine therapy for a
      defined period of time with or without bridging to alternative opioids.
      Additionally, social support people and patient motivation should be addressed
      and optimized, as well as nonopioid adjuvant therapy should be maximized as
      applicable to each patient undergoing a surgical or interventional pain
      procedure. KEY WORDS: Buprenorphine, naloxone, surgery, pain management,
      anesthesia, suboxone, opioid abuse.

PMID- 29357324
TI  - Circulating MiR-146a May be a Potential Biomarker of Coronary Heart Disease in
      Patients with Subclinical Hypothyroidism.
AB  - BACKGROUND/AIMS: Subclinical hypothyroidism (SCH) plays a crucial role in the
      development and progression of coronary heart disease (CHD). However, any
      associated changes in the circulating microRNAs (miRNAs) levels and slightly
      elevated thyroid stimulating hormone (TSH) levels in CHD patients are unknown.
      miR-146a is a well known miRNA associated with inflammatory autoimmune diseases.
      Here, we evaluated miR-146a expression in patients, with the goal of re
      evaluating the effect of SCH on CHD. METHODS: A total of 192 study subjects who
      underwent coronary angiography for either suspected or confirmed CHD were
      enrolled in 3 groups: CHD with SCH, CHD alone, and healthy controls. The
      circulating levels of miR-146a were quantified using qRT-PCR. RESULTS: Levels of
      miR-146a were positively correlated with CHD severity, as indicated by the
      Gensini score (r=0.354). The relative expression of miR-146a in the CHD+SCH, CHD
      and healthy control groups was 2.223+/-0.827, 1.588+/-0.726 and 0.632+/-0.309,
      respectively. Plasma TSH levels were positively correlated with miR-146a levels
      (r=0.321). According to multivariate logistic regression analyses, miR-146a
      levels were associated with the incidence of CHD in patients with SCH. For
      diagnosing CHD, the area under the ROC curve (AUC) of miR-146a and TSH was 0.779
      and 0.752, respectively. When the TSH and miR-146a levels were combined to form a
      composite panel, the AUC of the panel was 0.858. CONCLUSION: Plasma miR-146a
      levels correlated with the severity of coronary atherosclerosis and increased
      with TSH slightly elevated in patients with CHD. Thus, miR-146a may have good
      predictive value for CHD among individuals with elevated TSH levels.

PMID- 29357326
TI  - Fusion or Not for Degenerative Lumbar Spinal Stenosis: A Meta-Analysis and
      Systematic Review.
AB  - BACKGROUND: Degenerative lumbar spinal stenosis (DLSS) is the main cause for
      chronic low back pain in the elderly. When refractory to conservative treatment,
      symptomatic patients commonly undergo surgery. However, whether or not fusion is
      a relatively better surgical option still remains unclear. OBJECTIVE: The purpose
      of the present study was to systematically review the clinical outcomes of spinal
      decompression with or without spinal fusion for DLSS. STUDY DESIGN: A systematic
      review of the therapeutic effect for DLSS with or without fusion. METHODS: A
      literature search of 5 electronic databases was performed including PubMed,
      EMBASE, MEDLINE, Cochrane Library, and CENTRAL from inception to August 2016.
      Only randomized controlled trials (RCTs) assessing the comparison between
      decompression and fusion surgery for DLSS were included. RESULTS: A total of 5
      RCTs involving 438 patients met the inclusion criteria. Low-quality evidence of
      the meta-analysis was performed for the heterogeneity of the included studies.
      Pooled analysis showed no significant differences between decompression alone and
      fusion groups for the Oswestry Disability Index (ODI) scores at the baseline (P =
      0.50) and 2 years follow-up (P = 0.71), and the satisfaction rate of operations
      was also similar for the groups (P = 0.53). However, operation time (P = 0.002),
      blood loss (P < 0.00001), and length of hospital stay (P = 0.007) were remarkably
      higher in the fusion group. Furthermore, there was no difference in the
      reoperation rate between these 2 groups at the latest follow-up (P = 0.49).
      LIMITATION: The methodological criteria and sample sizes were highly variable.
      The studies were heterogeneous. CONCLUSION: The present meta-analysis is the
      first to compare the efficacy of decompression alone and spinal fusion for the
      treatment of DLSS, including 5 RCTs. Our results demonstrate that additional
      fusion surgery seems unlikely to result in better outcomes for patients with
      DLSS, but it may increase additional risks and costs. High-quality homogeneous
      research is required to provide further evidence about surgical procedures for
      patients with DLSS. KEY WORDS: Decompression, fusion, lumbar spinal stenosis,
      meta-analysis.

PMID- 29357327
TI  - Characteristics of the Middle Cervical Sympathetic Ganglion: A Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Understanding the characteristics of the middle cervical sympathetic
      ganglion (MCSG) may minimize procedure-related complications and maximize
      efficacy during surgery or ultrasound (US)-guided procedures. The location and
      detection rate of the MCSG were variable in small population studies. Therefore,
      a large population study or meta-analysis could give more information about the
      MCSG. OBJECTIVES: We aim to review the published literature and evaluate the
      anatomical features of the MCSG, including the detection rate, location, size,
      and a normal variation, and to review the clinical relevance of MCSG for
      procedures including, US-guided ganglion block, ethanol ablation (EA), or
      radiofrequency ablation (RFA). STUDY DESIGN: A systematic review and meta
      analysis. The Ovid-MEDLINE and EMBASE databases were searched to find the
      detection rate, location, and other characteristics of the MCSG. SETTING: The
      pooled proportions for the detection rate of the MCSG were assessed using the
      DerSimonian-Laird random-effects model. METHODS: Heterogeneity among the studies
      was determined using a chi-square analysis for the pooled estimates and
      inconsistency index (I2). In order to reduce the heterogeneity, sensitivity
      analyses were performed. RESULTS: A review of 542 studies identified 8 eligible
      studies, with 273 MCSGs included in the meta-analysis. The pooled proportion for
      the detection rate of the MCSG was 50.4% (95% confidence interval [CI], 34.5 -
      66.4%). Considerable heterogeneity among the studies was observed (I2 = 94.9%).
      In the sensitivity analysis, when excluding one study, heterogeneity was reduced
      with a recalculated pooled proportion of 44.2% (95% CI, 32.1 - 56.2%; I2 =
      86.0%). The location of the MCSG is usually posterior to the carotid sheath and
      anterior to the longus colli muscle at the level of the C3 - C7 vertebrae. There
      was a variant where the cervical sympathetic trunk was located at the posterior
      wall of the carotid sheath and was adherent to the sheath. The size of the MCSG
      is as follows: the width, length, and height ranges were 3.8 - 6.3 mm, 6.3 - 10.5
      mm, and 1.7 - 2.1 mm, respectively. A specific type of MCSG, referred to as the
      "double middle cervical ganglion", consisting of 2 ganglia, was demonstrated in 3
      studies with a detection rate of 2.9 - 10%. LIMITATIONS: This meta-analysis
      included a relatively small number of studies. Significant heterogeneity was also
      present in the detection rate of MCSG in these studies. There was a lack of
      concentrated information about the MCSG, because the majority of the included
      studies focused on the entire cervical sympathetic chain, not only MCSG
      primarily. Improving complication rates might be limited due to the approximate
      50% detection rate. CONCLUSION: Understanding the characteristics and variations
      of the MCSG could minimize complications and maximize efficacy during surgery and
      US-guided procedures. KEY WORDS: Middle cervical sympathetic ganglion, cervical
      sympathetic trunk, cervical sympathetic chain, ultrasound, nerve block, ethanol
      ablation, radiofrequency ablation, thyroid, Horner syndrome, meta-analysis.

PMID- 29357328
TI  - Efficacy of Pain Relief in Different Postherpetic Neuralgia Therapies: A Network
      Meta-Analysis.
AB  - BACKGROUND: Postherpetic neuralgia (PHN) is a nerve pain disease usually
      controlled by different therapies, i.e., topical therapies, antiepileptics,
      analgesics, antipsychotics, antidepressants, anti-dementia drugs, antivirals,
      amitriptyline, fluphenazine, and magnesium sulfate. It is believed that different
      therapies may lead to different levels of pain relief. OBJECTIVES: We proposed
      this study to compare the efficacy of PHN treatments. STUDY DESIGN: We conducted
      a systematic review of the current literature. All relevant studies were
      retrieved from online databases. The standardized mean difference (SMD) was used
      for pain relief measurement in different PHN therapies. SETTING: A conventional
      meta-analysis and a network meta-analysis (NMA) were carried out together with
      the surface under the cumulative ranking curve (SUCRA) for each therapy
      calculated regarding their efficacy. RESULTS: A pairwise meta-analysis suggested
      that 4 treatment classes, including topical therapies, antiepileptics,
      analgesics, and antidepressants, exhibited better pain relief results than
      placebo. Likewise, a NMA suggested that patients with 4 treatment classes
      exhibited significant improvements in pain scores compared to those with placebo.
      LIMITATIONS: There is a lack of direct head-to-head comparisons of some
      treatments, especially for antivirals, anti-dementia drugs, and magnesium
      sulfate. Secondly, the specific agents belonging to the same class of therapies
      might exhibit different effects (gabapentin and carisbamate) with different
      mechanisms (opioids and ketamine) on reducing pain, and some agents were hard to
      find in literatures and were not involved in our study, which may influence our
      results. CONCLUSIONS: Analgesics were preferable to other treatments with respect
      to pain relief for PHN, while antivirals appeared to be less effective than other
      therapies. KEY WORDS: Postherpetic neuralgia, topical agents, antiepileptics,
      analgesics, antipsychotics, antidepressants.

PMID- 29357329
TI  - Pulsed Radiofrequency Improves Neuropathic Pain in Chronic Constriction Injury
      Rats through the Upregulation of the Transcription and Translation Levels of
      Glial Cell Line-Derived Neurotrophic Factor.
AB  - BACKGROUND: Several studies in recent years have confirmed that the direct
      application of pulsed radiofrequency (PRF) on peripheral nerve compression points
      can alleviate hyperalgesia in animal models of neuropathic pain (NP). However,
      the mechanism underlying the treatment of peripheral nerves by PRF is unclear.
      OBJECTIVES: We aim to observe changes in pain behavior after the application of
      PRF on the ligation site of the sciatic nerves (SNs) of rats with chronic
      constriction injury (CCI) and to investigate the effects of PRF on the
      transcription and translation levels of glial cell line-derived neurotrophic
      factor (GDNF) in nerve tissues at the treatment site. STUDY DESIGN: A randomized,
      experimental trial. SETTING: Experimental Animal Center, Beijing Tiantan
      Hospital. METHODS: Ninety-six adult male Sprague-Dawley rats were randomly
      divided into 4 groups: sham-sham (SS) group, sham-PRF (SP) group, CCI-sham (CS)
      group, and CCI-PRF (CP) group. The right SNs of rats in the CS and CP group were
      ligated to establish the CCI model. The right SNs in the SS and SP groups were
      isolated and exposed but without being ligated. On the fourteenth day after
      CCI/sham operation, PRF treatment was performed on the midpoint of the ligation
      sites of the SN in the CP group and the corresponding sites in the SP group. The
      electrode was only placed at the ligation sites of the SN in the CS group and the
      corresponding sites in the SS group without current being applied. The 50% paw
      withdrawal threshold (50%PWT) and thermal withdrawal latency (TWL) of rats in all
      of the groups were measured. The transcription and translation levels of GDNF of
      the PRF/sham treatment sites were measured before and after treatment by reverse
      transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent
      assays (ELISAs). RESULTS: The 50%PWT value of the hind paws of rats in the CP
      group gradually increased on day 6 after the PRF treatment and was significantly
      higher than that in the CS group (6 days after treatment P < 0.05; 14 days after
      treatment P < 0.01). The TWL value in the CP group was higher than that in the CS
      group 2 days after treatment (P < 0.05) and was significantly higher (P < 0.01)
      from day 6 until the end of the experiment. On the day 6 and 14 after PRF
      treatment, the mRNA and protein expression levels of GDNF at the ligation sites
      of the SNs of rats in the CP group were higher than both the levels before
      treatment and those in the CS group (P < 0.01). LIMITATIONS: The efficacy of PRF
      treatment in the CCI model was only tested within 14 days, and the changes in
      GDNF levels were only tested at 3 time-points before and after treatment.
      CONCLUSIONS: The direct application of PRF on SN ligation sites in the CCI model
      can safely and effectively alleviate NP. One of the mechanisms of this effect
      could be the upregulation of the transcription and translation of GDNF in
      compressed SNs. KEY WORDS: Pulsed radiofrequency, chronic constriction injury,
      sciatic nerve, 50% paw withdrawal threshold, thermal withdrawal latency, glia
      cell line-derived neurotrophic factor, reverse transcription-polymerase chain
      reaction, enzyme-linked immunosorbent assay.

PMID- 29357330
TI  - Ultrasound-Guided Genicular Nerve Block for Knee Osteoarthritis: A Double-Blind,
      Randomized Controlled Trial of Local Anesthetic Alone or in Combination with
      Corticosteroid.
AB  - BACKGROUND: Recently, several studies suggested that radiofrequency (RF) ablation
      of the genicular nerves is a safe and effective therapeutic procedure for
      intractable pain associated with chronic knee osteoarthritis (OA). Diagnostic
      genicular nerve block (GNB) with local anesthetic has been generally conducted
      before making decisions regarding RF ablation. Although GNB has been recently
      performed together with corticosteroid, the analgesic effects of corticosteroids
      for treating chronic pain remain controversial. OBJECTIVES: The current study
      aims to assess the effects of combining corticosteroids and local anesthesia
      during ultrasound-guided GNB in patients with chronic knee OA. STUDY DESIGN: A
      randomized, double-blinded institutional study. SETTING: This study took place at
      Asan Medical Center in Seoul, Korea. METHODS: Forty-eight patients with chronic
      knee OA were randomly assigned to either the lidocaine alone group (n = 24) or
      lidocaine plus triamcinolone (TA) group (n = 24) before ultrasound-guided GNB.
      Visual analog scale (VAS), Oxford Knee Score (OKS), and global perceived effects
      (7-point scale) were assessed at baseline and at 1, 2, 4, and 8 weeks after the
      procedure. RESULTS: The VAS scores were significantly lower in the lidocaine plus
      TA group than in the lidocaine alone group at both 2 (P < 0.001) and 4 (P <
      0.001) weeks after GNB. The alleviation of intense pain in the lidocaine plus TA
      group was sustained up to 2 weeks after the procedure, in accordance with the
      definition of a minimal clinically important improvement. Although a similar
      intergroup difference in OKSs was observed at 4 weeks (P < 0.001), the clinical
      improvement in functional capacity lasted for only one week after the
      reassessment of OKSs, in accordance with a minimal important change. No patient
      reported any postprocedural adverse events during the follow-up period.
      LIMITATIONS: The emotional state of the patients, which might affect the
      perception of knee pain, was not evaluated. The follow-up period was 2 months;
      this period might be insufficient to validate the short-term effects of GNB.
      CONCLUSIONS: Ultrasound-guided GNB, when combined with a local anesthetic and
      corticosteroid, can provide short-term pain relief. However, the clinical benefit
      of corticosteroid administration was not clear in comparison with local
      anesthesia alone. Given the potential adverse effects, corticosteroids might not
      be appropriate as adjuvants during a GNB for chronic knee OA.The study protocol
      was approved by our institutional review board (2012-0210), and written informed
      consent was obtained from all patients. The trial was registered with the
      Clinical Research Information Service (KCT 0001139). KEY WORDS: Chronic pain,
      knee osteoarthritis, genicular nerve block, ultrasound, corticosteroid, local
      anesthetic, visual analog scale, Oxford Knee Score.

PMID- 29357331
TI  - Reducing Radiation Exposure in Lumbar Transforaminal Epidural Steroid Injections
      with Pulsed Fluoroscopy: A Randomized, Double-blind, Controlled Clinical Trial.
AB  - BACKGROUND: Fluoroscopy-guided lumbar transforaminal epidural steroid injections
      (L-TFESI) result in radiation exposure that carries risks to patients,
      physicians, and procedural staff. OBJECTIVE: We aim to evaluate the feasibility
      of using pulsed fluoroscopy to safely reduce radiation exposure during L-TFESI.
      STUDY DESIGN: This is a prospective, double-blind, randomized controlled trial.
      SETTING: This study took place in a single-center, academic, outpatient
      interventional pain management clinic. METHODS: Patients undergoing L-TFESI were
      randomly assigned to either continuous mode fluoroscopy (high-dose), pulsed
      fluoroscopy with 8 pulses per second (medium-dose), or pulsed fluoroscopy with
      one pulse per second (low-dose). Data on radiation doses and other clinical and
      demographic factors were also collected. RESULTS: In total, 231 cases were
      analyzed in the high-dose group (n = 81), medium-dose group (n = 72), and low
      dose group (n = 78). Mean radiation effective dose (uSv) was 121 in the high-dose
      group, 57.9 in the medium-dose group, and 34.8 in the low-dose group (P < 0.001).
      The incidence of inadequate image quality in the pulsed groups was 6% (9/150).
      The body mass index (BMI, mean +/- SD) was significantly higher in patients with
      inadequate image quality (37.3 +/- 7.2) than with adequate quality (30.5 +/- 7.2,
      P = 0.005). LIMITATIONS: Radiation doses were measured using the meter on C-arm
      fluoroscopes rather than by direct measurement. CONCLUSIONS: The use of pulsed
      fluoroscopy during L-TFESI resulted in radiation dose reduction of up to 72.1%
      without causing any significant adverse events. Pulsed fluoroscopy should be
      considered as an initial fluoroscopic setting for L-TFESI to reduce radiation
      exposure. KEY WORDS: Radiation, epidural, fluoroscopy, injection, exposure,
      pulse.

PMID- 29357333
TI  - Implication of Two Different Doses of Intradiscal Ozone-Oxygen Injection upon the
      Pain Alleviation in Patients with Low Back Pain: A Randomized, Single-Blind
      Study.
AB  - BACKGROUND: Low back pain (LBP) is mostly induced by disc herniation (DH) or
      degeneration and has a burden upon social activity and economical aspects of
      life. An abundance of medical and surgical interventions have evolved to resolve
      this problem, but one of the newly introduced techniques, which is the minimally
      invasive, low cost ozone-oxygen mixture (O3-O2) intradiscal injection, offers a
      rapid onset amelioration of symptoms with a sustained duration of pain relief.
      OBJECTIVE: We aim to evaluate the quality of pain alleviation using 2 different
      doses of intradiscal injections of O3-O2 mixture. STUDY DESIGN: A prospectively
      randomized, single-blind study. SETTING: Pain clinic, anesthesia, intensive care,
      and pain department in Assiut University Hospitals. METHODS: Sixty patients with
      symptomatizing single lumbar DH were subjected to O3-O2 intradiscal injection and
      randomly allocated into one of 2 groups; group A: received 10 mL, 40 ug/mL of O3
      O2 and group B: received 10 mL, 30 ug/mL of O3-O2. Pain score and functional
      ability of the patients using the visual analog scale (VAS) and Oswestry
      Disability Index (ODI) were evaluated after 1, 6, and 12 months and compared to
      the basal values. Patient satisfaction and reduction of DH were evaluated after
      the sixth month. RESULTS: There were no significant differences between the 2
      groups regarding the clinical outcome; however both the ODI and VAS evaluations
      showed highly significant improvement (decreased) (P < 0.01) after injection and
      during the entire follow-up period. There were highly significant negative
      correlations between the DH reduction percentage and both the VAS and ODI scores
      after 6 months in both of the groups. LIMITATIONS: This study was limited by a
      small sample size; it was also an active control trial, which may explain the
      insignificant difference in between the groups, in addition to being a single
      blind trial. CONCLUSION: Intradiscal injection of O3-O2 mixture is a very
      valuable maneuver in the reduction of DH size and improvement of pain quality,
      with either ozone concentrations of 40 ug/mL or 30 ug/mL. KEY WORDS: Low back
      pain, ozone, disc herniation.

PMID- 29357332
TI  - Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A
      Randomized Cross-Over Study.
AB  - BACKGROUND: Pain, fatigue, and concentration difficulties are typical features of
      chronic fatigue syndrome (CFS). The exact underlying mechanisms of these symptoms
      are still unknown, but available evidence suggests an important role for impaired
      pain modulation. As evidence also suggests that pain modulation is related to
      cardiovascular mechanisms, it seems logical to investigate whether cerebral blood
      flow (CBF) and heart rate variability (HRV) are altered in these patients.
      OBJECTIVES: We aimed to investigate the role of the cardiovascular system in pain
      modulation and symptoms of CFS; the response of CBF and HRV to physical stress
      and their relation to the change in temporal summation (TS) of pressure pain and
      self-reported symptoms was evaluated. STUDY DESIGN: A controlled, randomized
      cross-over trial. SETTING: University Hospital Brussels. METHODS: Twenty CFS
      patients and 20 sedentary healthy controls were included in this study. In both
      of the groups, the change in TS of pressure pain, CBF (using transcranial
      Doppler), and HRV (using finger plethysmography) was examined during physical and
      emotional stress (to control for potential bias), as well as their association
      mutually and with self-reported symptoms of pain, fatigue, and concentrations
      difficulties. RESULTS: There was no significant interaction or group (F-values
      ranging from .100 to 1.862, P-values ranging from .754 to .181) effect in CBF or
      HRV parameters. HRV and CBF did change during physical exercise, but the changes
      did not differ between patients and controls. While pain scores during TS at the
      trapezius site reduced in the control group after the physical exercise protocol
      (P = .037), they did not change in the CFS group (P = .108), suggesting impaired
      pain modulation. There were no significant correlations between CBF, HRV, TS, and
      self-reported symptoms (all P-values of correlation analyses > .01). LIMITATIONS:
      Although effect sizes were medium to large, the study sample was relatively low.
      Also, the mild nature of the exercise bout is discussable. Nonetheless, this mild
      exercise was able to provoke endogenous pain modulation in the control group,
      which endorsed a proper execution of the cycling exercise. Moreover, mild
      exercises are more applicable to daily physical activities in CFS patients than
      vigorous exercises. CONCLUSION: These results seem to refute the previously
      suggested alterations of CBF/HRV in CFS patients. These cardiovascular parameters
      appear not to explain pain before, during, and following exercise. KEY WORDS:
      Chronic pain, physical exercise, emotional stress, pain modulation,
      cardiovascular systems, temporal summation, pain pressure thresholds,
      transcranial Doppler, plethysmography.

PMID- 29357334
TI  - Sacroiliac Joint Intraarticular Injection in True Anteroposterior View:
      Description of a New C-Arm Guided Method.
AB  - BACKGROUND: The anatomic characteristics of the sacroiliac joint (SIJ) make it
      difficult to achieve intraarticular injection without radiologic guidance. The
      classic C-arm guided SIJ intervention technique is difficult. Here we describe a
      new and simple method for SIJ intraarticular intervention. OBJECTIVE: This study
      aims to introduce a new, simple approach for SIJ intraarticular intervention.
      STUDY DESIGN: An observational case series study. SETTING: The study was
      conducted at an academic medical center in a major metropolitan city. METHODS:
      This method of intervention was performed on 57 patients (a total of 73 joints)
      who were selected for diagnostic and therapeutic SIJ intervention. The procedure
      was done in anteroposterior (AP) view, without any C-arm angulation. The accuracy
      of the intraarticular injection was confirmed by using intraarticular contrast
      material. A numerical rating scale (NRS) score was recorded for each joint before
      and after the procedure; the number of x-ray exposures and number of attempts
      were recorded for each procedure as well. RESULTS: Successful intraarticular
      contrast spread was obtained in all SIJs. The number of x-ray exposures was about
      9 +/- 3, and there was not a remarkable difference between cases according to
      gender of the patient (P = 0.1) or side of the joint (P = 0.2). In 5 cases, the
      first needle placement was not correct; there were no differences between gender
      (P = 0.4) and side of the joint (P = 0.4) regarding the first successful attempt.
      The NRS pain scores decreased in all of the patients more than 50% after the
      procedure; the pain scores were similar to the results of classic methods of
      intraarticular interventions with successful contrast spread, and there were no
      remarkable differences considering gender (P = 0.5) or side of the joint (P =
      0.8). LIMITATIONS: This is a very small, nonrandomized, and controlled study;
      further blinded clinical trials are needed to clarify the probable advantages of
      this method compared with conventional ones. CONCLUSION: This observational study
      introduces a new and simple approach for SIJ intraarticular intervention, with a
      high success rate. KEY WORDS: Low back pain, sacroiliac joint, C-arm, new
      technique, intraarticular, injection.

PMID- 29357335
TI  - Outcome of Transforaminal Epidural Steroid Injection According to the Severity of
      Lumbar Foraminal Spinal Stenosis.
AB  - BACKGROUND: Lumbar foraminal spinal stenosis (LFSS) is a common cause of
      radicular pain in the lower extremities. Transforaminal epidural steroid
      injection (TFESI) is being used widely for controlling radicular pain induced by
      LFSS. The efficacy of TFESI has been demonstrated in previous studies. However,
      no study has evaluated the outcome of TFESI according to the severity of LFSS.
      OBJECTIVE: In this study, we evaluated the outcome of TFESI in patients with
      chronic lumbar radicular pain due to LFSS according to the severity of LFSS by
      using magnetic resonance imaging (MRI). STUDY DESIGN: A prospective observational
      study. SETTING: A university hospital. METHODS: Sixty patients with chronic
      lumbar radicular pain due to LFSS were included in this prospective study and
      received TFESI at our university hospital. Three patients were lost to follow-up.
      On the basis of sagittal lumbar MRI findings, we assigned patients with mild to
      moderate LFSS to group A (n = 31) and those with severe LFSS to group B (n = 26).
      Pain intensity was evaluated using a numeric rating scale (NRS) before treatment
      and at 1, 2, and 3 months after treatment. RESULTS: Compared to pretreatment NRS
      scores, a significant decrease in NRS scores was observed in patients in both
      groups at 1, 2, and 3 months after treatment (P = 0.000). However, reductions in
      the NRS scores over time were significantly larger in group A (P = 0.023). Three
      months after treatment, 27 patients (87.1%) in group A and 11 patients (42.3%) in
      group B reported successful pain relief (pain relief of>/= 50%). LIMITATIONS:
      This study had a small number of patients. CONCLUSIONS: After TFESI, chronic
      lumbar radicular pain was significantly reduced regardless of the severity of
      LFSS, and the effects of TFESI were sustained for at least 3 months after
      treatment. However, the outcome of TFESI was superior in the group with a mild to
      moderate degree of LFSS, compared to the group with a severe degree of LFSS. We
      believe that our study provides useful information for establishing a treatment
      plan for radicular pain due to LFSS. KEY WORDS: Lumbar foraminal spinal stenosis,
      transforaminal epidural steroid injection, disease severity, magnetic resonance
      imaging, numeric rating scale, corticosteroids.

PMID- 29357336
TI  - The Termination Level of the Dural Sac Relevant to Caudal Epidural Block in
      Lumbosacral Transitional Vertebrae: A Comparison between Sacralization and
      Lumbarization Groups.
AB  - BACKGROUND: Lumbosacral transitional vertebrae (LSTV) are a relatively common
      variant and have been considered as one of the reasons for back pain. It is not
      unusual for clinicians to encounter patients with LSTV who require caudal
      epidural block (CEB) for pain management. OBJECTIVE: We investigated the
      termination level of the dural sac (DS) and anatomical features of the
      lumbosacral region relevant to CEB in patients with LSTV and compared these
      findings between sacralization and lumbarization groups. STUDY DESIGN: A
      retrospective evaluation. SETTING: A university hospital with inpatient and
      outpatient LSTV cases presenting low back pain. METHODS: Four hundred ninety-four
      LSTV patients were included and categorized into sacralization (n = 201) or
      lumbarization groups (n = 293). Magnetic resonance imaging (MRI) of all of the
      LSTV patients were reviewed to determine the level of DS termination, the
      shortest distance between the apex of the sacral hiatus and DS, and the presence
      and the caudal level of sacral perineural cysts. Each lumbosacral vertebra column
      was divided into 3 equal portions (upper, middle, and lower thirds). The MRI
      findings in both of the groups were compared and analyzed. RESULTS: The
      distribution frequency of the levels of DS termination demonstrated a significant
      difference between the 2 groups. The mean caudal DS level in the lumbarization
      group was significantly lower than the sacralization group (lower third of the S2
      [131 {44.7%} of 293 patients] vs. lower third of the S1 [78 {38.8%} of 201
      patients]). The DS terminated at the S3 in more than 19% of the lumbarization
      group, whereas in only one case of the sacralization group. Although the
      incidence of perineural cysts was not significantly different between the 2
      groups, the mean level of caudal margin of perineural cysts in the lumbarization
      group was significantly lower than the sacralization group (middle third of the
      S3 [10 {35.7%} of 28 cases] vs. middle third of the S2 [11 {44%} of 25 cases]).
      LIMITATIONS: This study reveals several limitations including the practical
      challenge of accurate enumeration of the transitional segment and the constraints
      on generalizability posed by the single-country study. CONCLUSION: When planning
      CEB for patients with LSTV, pre-procedural MRI to check the anatomical
      structures, including the level of DS termination and caudal margin of perineural
      cysts, would be of great use for lowering the risk of unexpected dural puncture
      during the procedure, especially in the lumbarization cases. KEY WORDS:
      Termination of the dural sac, dural sac termination, lumbosacral transitional
      vertebrae, transitional vertebra, caudal epidural block.

PMID- 29357337
TI  - Dual Site Pudendal Nerve Infiltration: More than Just a Diagnostic Test?
AB  - BACKGROUND: Pudendal neuralgia (PN) is a very painful and often disabling
      condition in which pudendal nerve blocks play an important role in both the
      diagnosis and management of PN. Some previous reports have advocated the use of
      pudendal nerve infiltration (PNI) as a diagnostic test only. OBJECTIVE: We aim to
      assess the outcomes of patients with typical refractory PN who underwent dual
      site computed tomography (CT)-guided pudendal nerve infiltration. STUDY DESIGN: A
      bicentric, retrospective cohort analysis. SETTING: An academic practice. METHODS:
      Between 2002 and 2016, 385 PNIs were performed in 195 patients in the 2 units.
      Only patients suffering from typical clinical PN were included, and only the
      first infiltration in each patient was considered for analysis. Therefore, 95
      patients who underwent 155 procedures were assessed. Pain was assessed using a
      visual analog scale (0-10) and self-reported estimated improvement (SRI),
      expressed as a percentage. Efficacy of the procedure was assessed at 1, 3, and 6
      months after procedure follow-up, and clinical success was defined as a 50%
      decrease of the VAS score. All procedures were performed under CT guidance and on
      an outpatient basis. Dual site infiltration was performed in each case at both
      the ischial spine and intra-Alcock's canal sites using a mixture of fast- and
      slow-acting anesthetic (1 mL lidocaine hydrochloride 1% and 2 mL ropivacaine
      chlorhydrate) along with a half dose of 1.5 mL of cortivazol (3.75 mg). RESULTS:
      Clinical success at one month post-procedure was present in 63.2% of patients
      (60/95) with a mean VAS score of 2.07 (P < 0.05) and a mean SRI of 71%. At 3
      months follow-up, clinical success was still present in 50.5% of patients (48/95)
      with a mean VAS score of 2.90/10 (P < 0.05) and a mean SRI of 62.3%. At 6 months
      follow-up, the efficacy rate decreased to 25.2% with a mean VAS score of 3.2/10
      and SRI of 60%. LIMITATIONS: The retrospective aspect of the study is a
      limitation, as well as the lack of a control group. CONCLUSION: Dual site PNI
      under CT guidance may offer significant mid-term pain relief to a majority of
      patients suffering from typical refractory PN. KEY WORDS: Pudendal nerve,
      neuralgia, block, Alcock, CT, guidance.

PMID- 29357338
TI  - Risk Factors for the Occurrence of Insufficient Cement Distribution in the
      Fractured Area after Percutaneous Vertebroplasty in Osteoporotic Vertebral
      Compression Fractures.
AB  - BACKGROUND: Insufficient cement distribution (ICD) in the fractured area has been
      advocated to be responsible for unsatisfied pain relief after percutaneous
      vertebroplasty (PVP) for osteoporotic vertebral compression fractures (OVCFs).
      However, little is known about risk factors for the occurrence of ICD. OBJECTIVE:
      The present study aimed to identify independent risk factors of the emergence of
      ICD. STUDY DESIGN: A retrospective cohort study. SETTING: Department of spinal
      surgery, an affiliated hospital of a medical university. METHODS: Patients who
      underwent PVP for single-level OVCF from January 2012 to September 2014 and met
      this study's inclusion criteria were retrospectively reviewed. Associations of
      ICD with co-variates (age, gender, bone mass density with a T-score, amount of
      injected cement, cement leakage, fracture level, fracture age, fracture severity
      grade, and location of the fractured area) and the influence of ICD on pain
      relief were analyzed. RESULTS: A total of 225 patients were included. ICD was
      found in 26 (11.6%) patients. Fractured area located in the superior portion of
      the index vertebra was significantly associated with occurrence of ICD. No
      further significant associations between the studied co-variates and emergence of
      ICD were seen in the adjusted analysis. In addition, patients with ICD had
      significantly higher immediate postoperative visual analog scale scores of back
      pain compared with those with sufficient cement distribution in the fractured
      area. LIMITATION: Location of the fractured area and cement distribution in the
      fractured area could not be evaluated quantitatively. CONCLUSIONS: The incidence
      of ICD is higher in patients with the fractured area located in the superior
      portion of the index vertebra and ICD might be responsible for unsatisfied pain
      relief after PVP for OVCFs. KEY WORDS: Percutaneous vertebroplasty, insufficient
      cement distribution, fractured area, risk factor, osteoporosis, vertebral
      compression fracture, spine, unsatisfied pain relief, cement augmentation.

PMID- 29357339
TI  - Do Pain Medicine Fellowship Programs Provide Education in Practice Management? A
      Survey of Pain Medicine Fellowship Programs.
AB  - BACKGROUND: We hypothesized that there is a gap between expectations and actual
      training in practice management for pain medicine fellows. Our impression is that
      many fellowships rely on residency training to provide exposure to business
      education. Unfortunately, pain management and anesthesiology business education
      are very different, as the practice settings are largely office- versus hospital
      based, respectively. OBJECTIVE: Because it is unclear whether pain management
      fellowships are providing practice management education and, if they do, whether
      the topics covered match the expectations of their fellows, we surveyed pain
      medicine program directors and fellows regarding their expectations and training
      in business management. STUDY DESIGN: A survey. SETTING: Academic pain medicine
      fellowship programs. METHODS: After an exemption was obtained from the University
      of Texas Medical Branch Institutional Review Board (#13-030), an email survey was
      sent to members of the Association of Pain Program Directors to be forwarded to
      their fellows. Directors were contacted 3 times to maximize the response rate.
      The anonymous survey for fellows contained 21 questions (questions are shown in
      the results). RESULTS: Fifty-nine of 84 program directors responded and forwarded
      the survey to their fellows. Sixty fellows responded, with 56 answering the
      survey questions. LIMITATIONS: The responder rate is a limitation, although
      similar rates have been reported in similar studies. CONCLUSIONS: The majority of
      pain medicine fellows receive some practice management training, mainly on
      billing documentation and preauthorization processes, while most do not receive
      business education (e.g., human resources, contracts, accounting/financial
      reports). More than 70% of fellows reported that they receive more business
      education from industry than from their fellowships, a result that may raise
      concerns about the independence of our future physicians from the industry. Our
      findings support the need for enhanced and structured business education during
      pain fellowship. KEY WORDS: Business education, practice management, fellowship
      training, curriculum development, knowledge gaps, private practice.

PMID- 29357340
TI  - Chronic Smoking is Not Associated with Increased Postoperative Opioid Use in
      Patients with Lung Cancer or Esophageal Cancer.
AB  - BACKGROUND: Chronic smokers show differences in pain sensitivity compared to
      healthy non-smokers. Yet, no study to date has examined whether smoker status has
      an effect on postoperative pain. OBJECTIVE: We aim to examine a possible
      correlation between preoperative smoking and postoperative opioid dose based on
      the hypothesis that smokers would use higher doses of opioids to manage increased
      postoperative pain. STUDY DESIGN: A retrospective observational cohort study.
      SETTING: The National Cancer Center in Korea. METHODS: We examined medical record
      data for patients who had undergone curative resection for either lung or
      esophageal cancer (lobectomy or bilobectomy for lung cancer or an Ivor Lewis
      operation for esophageal cancer) between January 1, 2006 and December 31, 2010.
      We examined the correlation between the total preoperative average number of
      packs per day multiplied by years of cigarette smoking (pack-years) and morphine
      equivalent daily doses administered to patients after surgery, considering each
      type of cancer both individually and together. Partial correlation and regression
      analyses were performed to determine the causality of a possible relationship
      between pack-years of cigarette smoking and postoperative opioid dose. RESULTS: A
      total of 1,129 patients (871 patients with lung cancer and 258 patients with
      esophageal cancer) were included in the final analysis. There was no significant
      correlation between total pack-years of cigarette smoking and postoperative
      opioid dose for lung cancer, esophageal cancer, or both cancer types combined (r
      = 0.042, -0.012, and 0.037, respectively). In the analysis of both cancer types
      combined, video-assisted thoracic surgery (VATS) was associated with an 11.1%
      decrease in opioid dose (beta = -0.111, P = 0.003) and epidural analgesia was
      associated with a 7.2% increase in opioid dose (beta = 0.072, P = 0.042).
      LIMITATIONS: The retrospective design of this study is a limitation. CONCLUSION:
      Our study did not observe a correlation between preoperative smoking and
      postoperative opioid dose in patients with lung or esophageal cancer. KEY WORDS:
      Smoking, postoperative pain, opioid, lung cancer, esophageal cancer, analgesia.

PMID- 29357341
TI  - The Effect of Caudal Epidural Pulsed Radiofrequency Stimulation in Patients with
      Refractory Chronic Idiopathic Axonal Polyneuropathy.
AB  - BACKGROUND: Many patients with chronic idiopathic axonal polyneuropathy (CIAP)
      suffer from neuropathic pain, which is managed using several oral medications and
      modalities. However, despite these treatments, pain persists in some patients.
      OBJECTIVE: In the clinical field, clinicians frequently meet patients with
      neuropathic pain caused by CIAP. The authors investigated the effect of caudal
      epidural pulsed radiofrequency (PRF) for the management of CIAP-induced
      refractory neuropathic pain. STUDY DESIGN: This is a prospective study. SETTING:
      The outpatient clinic of a single academic medical center in KoreaMETHODS: Twenty
      patients with neuropathic pain and a diagnosis of refractory CIAP were recruited.
      For PRF stimulation, a 22-gauge cannula was inserted into the epidural space
      through the sacral hiatus under fluoroscopic guidance. PRF stimulation was
      administered once at 5 Hz with a 5-ms pulse width for 600 seconds at 55 V. The
      effect of stimulation was evaluated using a numeric rating scale (NRS) at 2 weeks
      and 1, 2, and 3 months after the procedure. Successful pain relief was defined as
      a reduction in the NRS score of>/= 50% as compared with the score prior to
      treatment. In addition, at 3 months after treatment, patient satisfaction levels
      were examined; patients that reported "very good" (score = 7) or "good" (score =
      6) results were considered to be satisfied with the procedure. RESULTS:
      Neuropathic pain was significantly reduced at 2 weeks and at 1, 2, and 3 months
      follow-up after PRF (P < 0.001, repeated measures one-factor analysis). In
      addition, at 3 months post-PRF, half of the patients achieved a successful
      response (>/= 50% pain reduction) and were satisfied with treatment results.
      LIMITATIONS: A small number of patients were recruited, and we did not perform
      long-term follow-up. CONCLUSION: Caudal epidural PRF may be a good treatment
      option for managing neuropathic pain induced by CIAP, especially when pain is
      unresponsive to oral medications. KEY WORDS: Pulsed radiofrequency, chronic
      idiopathic axonal neuropathy, caudal epidural stimulation, neuropathic pain
      chronic pain, refractory pain.

PMID- 29357342
TI  - Early Experience of Full-Endoscopic Interlaminar Discectomy for Adolescent Lumbar
      Disc Herniation with Sciatic Scoliosis.
AB  - BACKGROUND: Full-endoscopic interlaminar discectomy (FEID) has achieved
      satisfactory outcome in adolescent lumbar disc herniation (ALDH). Sciatic
      scoliosis is found to be a common presentation in ALDH. However, few reports are
      focused on the influences of sciatic scoliosis on ALDH and the prognosis of
      sciatic scoliosis after FEID. OBJECTIVE: This study aims to evaluate the clinical
      and radiological results of FEID in the treatment of ALDH with sciatic scoliosis
      and to identify the effects of sciatic scoliosis on complication and recurrence.
      STUDY DESIGN: A retrospective study. SETTING: An inpatient surgery center.
      METHODS: A series of cases of patients under age 20 with single-level ALDH that
      underwent FEID between January 2010 and December 2014 were retrospectively
      analyzed. The patients were divided into 2 groups according to if they had
      scoliosis or not. Clinical outcomes were evaluated using a visual analog scale
      (VAS) for low back and leg pain, Oswestry Disability Index (ODI) for the
      functional assessment, and modified Macnab criteria for the patient satisfaction.
      Radiological parameters of the scoliosis group such as Cobb angle, CVSL-max, and
      CVSL-C7 were statistically analyzed. RESULTS: No significant differences were
      found between both groups in terms of the mean operative time, the mean length of
      hospital stay, complications, and recurrences (P > 0.05). VAS and ODI scores were
      significantly improved in both groups (P < 0.05). However, there were no
      statistically significant differences between the 2 groups in VAS, ODI, and
      modified MacNab criteria (P > 0.05). For the scoliosis group, significant
      improvements were observed in the postoperative sagittal and coronal alignment
      parameters (P < 0.05). LIMITATIONS: This was a retrospective study with a
      relatively small sample size. Additionally, the length of follow-up was short.
      CONCLUSIONS: The application of FEID in the treatment of ALDH could achieve
      satisfactory clinical and radiological outcomes. Sciatic scoliosis was corrected
      spontaneously without increasing the risk of complication and recurrence. KEY
      WORDS: Adolescent lumbar disc herniation, full-endoscopic interlaminar
      discectomy, sciatic scoliosis, recurrence.

PMID- 29357343
TI  - Long-term Clinical Effects of DiscoGel for Cervical Disc Herniation.
AB  - BACKGROUND: Radiopaque gelified ethanol (RGE; DiscoGel, Gelscom SAS, France) is
      used as a chemonucleolysis substance in treating intradiscal herniation, showing
      good results without complications. It has also been used in cervical disc
      herniations (CDHs), demonstrating the potential efficacy of this substance.
      OBJECTIVE: The aim of the study is to investigate the long-term effectiveness and
      safety of DiscoGel in patients with CDH and chronic neck pain. STUDY DESIGN: This
      is a cross-sectional, single-center study. SETTING: The study was conducted from
      November 2013 to May 2016 on patients visiting Sakarya University Training and
      Research Hospital's pain clinic . METHODS: Each patient was evaluated before the
      procedure (baseline) and at 1, 3, 6, and 12 months after the procedure, using the
      visual analog scale (VAS) score for pain, the Oswestry Disability Index score to
      measure degree of disability, and estimate quality of life for those with pain;
      this coincides with scores on the Neuropathic Pain Questionnaire (DN4) for
      differential diagnoses. RESULTS: Thirty-three patients with CDH underwent the
      same treatment with DiscoGel between November 2013 and May 2016. Significant pain
      relief was noted, as opposed to preoperative pain, at 1, 3, 6, and 12 months
      after the procedure according to each patient's self-evaluation (P = 0.01).
      Differences in VAS, ODI, and DN4 scores between 1, 3, 6, and 12 months with the
      same variables were not statistically significant. There were no complications
      with the procedure. LIMITATIONS: Our study was conducted retrospectively, which
      led to problems with long-term follow-up data. In addition, this study was
      performed with a small group of patients. CONCLUSIONS: RGE is a potential
      alternative to surgery for patients with pain at the cervical level. However, we
      concluded that more studies with longer follow-up intervals with RGE will be
      necessary for assessment of the technique's efficiency. KEY WORDS: Cervical pain,
      herniation, neuropathic pain, injection, DiscoGel, chemonucleolysis.

PMID- 29357344
TI  - The Perils of Overestimating the Efficacy of Cannabis-Based Medicines for Chronic
      Pain Management.

PMID- 29357345
TI  - In Response: Aviram J et al The Perils of Overestimating the Efficacy of Cannabis
      Based Medicines for Chronic Pain Management.

PMID- 29357346
TI  - Magnesium Efficacy to Improve Analgesic Effects of Transversus Abdominis Plane
      Blocks.

PMID- 29357347
TI  - In Response: Magnesium Efficacy to Improve Analgesic Effects of Transversus
      Abdominis Plane Blocks.

PMID- 29357348
TI  - Evolution of mitotic spindle behavior during the first asymmetric embryonic
      division of nematodes.
AB  - Asymmetric cell division is essential to generate cellular diversity. In many
      animal cells, the cleavage plane lies perpendicular to the mitotic spindle, and
      it is the spindle positioning that dictates the size of the daughter cells.
      Although some properties of spindle positioning are conserved between distantly
      related model species and different cell types, little is known of the
      evolutionary robustness of the mechanisms underlying this event. We recorded the
      first embryonic division of 42 species of nematodes closely related to
      Caenorhabditis elegans, which is an excellent model system to study the
      biophysical properties of asymmetric spindle positioning. Our recordings,
      corresponding to 128 strains from 27 Caenorhabditis and 15 non-Caenorhabditis
      species (accessible at http://www.ens-lyon.fr/LBMC/NematodeCell/videos/),
      constitute a powerful collection of subcellular phenotypes to study the evolution
      of various cellular processes across species. In the present work, we analyzed
      our collection to the study of asymmetric spindle positioning. Although all the
      strains underwent an asymmetric first cell division, they exhibited large intra-
      and inter-species variations in the degree of cell asymmetry and in several
      parameters controlling spindle movement, including spindle oscillation,
      elongation, and displacement. Notably, these parameters changed frequently during
      evolution with no apparent directionality in the species phylogeny, with the
      exception of spindle transverse oscillations, which were an evolutionary
      innovation at the base of the Caenorhabditis genus. These changes were also
      unrelated to evolutionary variations in embryo size. Importantly, spindle
      elongation, displacement, and oscillation each evolved independently. This
      finding contrasts starkly with expectations based on C. elegans studies and
      reveals previously unrecognized evolutionary changes in spindle mechanics.
      Collectively, these data demonstrate that, while the essential process of
      asymmetric cell division has been conserved over the course of nematode
      evolution, the underlying spindle movement parameters can combine in various
      ways. Like other developmental processes, asymmetric cell division is subject to
      system drift.

PMID- 29357349
TI  - Knockdown of wfs1, a fly homolog of Wolfram syndrome 1, in the nervous system
      increases susceptibility to age- and stress-induced neuronal dysfunction and
      degeneration in Drosophila.
AB  - Wolfram syndrome (WS), caused by loss-of-function mutations in the Wolfram
      syndrome 1 gene (WFS1), is characterized by juvenile-onset diabetes mellitus,
      bilateral optic atrophy, and a wide spectrum of neurological and psychiatric
      manifestations. WFS1 encodes an endoplasmic reticulum (ER)-resident transmembrane
      protein, and mutations in this gene lead to pancreatic beta-cell death induced by
      high levels of ER stress. However, the mechanisms underlying neurodegeneration
      caused by WFS1 deficiency remain elusive. Here, we investigated the role of WFS1
      in the maintenance of neuronal integrity in vivo by knocking down the expression
      of wfs1, the Drosophila homolog of WFS1, in the central nervous system. Neuronal
      knockdown of wfs1 caused age-dependent behavioral deficits and neurodegeneration
      in the fly brain. Knockdown of wfs1 in neurons and glial cells resulted in
      premature death and significantly exacerbated behavioral deficits in flies,
      suggesting that wfs1 has important functions in both cell types. Although wfs1
      knockdown alone did not promote ER stress, it increased the susceptibility to
      oxidative stress-, excitotoxicity- or tauopathy-induced behavioral deficits, and
      neurodegeneration. The glutamate release inhibitor riluzole significantly
      suppressed premature death phenotypes induced by neuronal and glial knockdown of
      wfs1. This study highlights the protective role of wfs1 against age-associated
      neurodegeneration and furthers our understanding of potential disease-modifying
      factors that determine susceptibility and resilience to age-associated
      neurodegenerative diseases.

PMID- 29357350
TI  - Hippo signaling controls cell cycle and restricts cell plasticity in planarians.
AB  - The Hippo pathway plays a key role in regulating cell turnover in adult tissues,
      and abnormalities in this pathway are consistently associated with human cancers.
      Hippo was initially implicated in the control of cell proliferation and death,
      and its inhibition is linked to the expansion of stem cells and progenitors,
      leading to larger organ size and tumor formation. To understand the mechanism by
      which Hippo directs cell renewal and promotes stemness, we studied its function
      in planarians. These stem cell-based organisms are ideal models for the analysis
      of the complex cellular events underlying tissue renewal in the whole organism.
      hippo RNA interference (RNAi) in planarians decreased apoptotic cell death,
      induced cell cycle arrest, and could promote the dedifferentiation of postmitotic
      cells. hippo RNAi resulted in extensive undifferentiated areas and overgrowths,
      with no effect on body size or cell number. We propose an essential role for
      hippo in controlling cell cycle, restricting cell plasticity, and thereby
      preventing tumoral transformation.

PMID- 29357351
TI  - Identification of osmoadaptive strategies in the halophile, heterotrophic ciliate
      Schmidingerothrix salinarum.
AB  - Hypersaline environments pose major challenges to their microbial residents.
      Microorganisms have to cope with increased osmotic pressure and low water
      activity and therefore require specific adaptation mechanisms. Although
      mechanisms have already been thoroughly investigated in the green alga Dunaliella
      salina and some halophilic yeasts, strategies for osmoadaptation in other
      protistan groups (especially heterotrophs) are neither as well known nor as
      deeply investigated as for their prokaryotic counterpart. This is not only due to
      the recent awareness of the high protistan diversity and ecological relevance in
      hypersaline systems, but also due to methodological shortcomings. We provide the
      first experimental study on haloadaptation in heterotrophic microeukaryotes,
      using the halophilic ciliate Schmidingerothrix salinarum as a model organism. We
      established three approaches to investigate fundamental adaptation strategies
      known from prokaryotes. First, proton nuclear magnetic resonance (1H-NMR)
      spectroscopy was used for the detection, identification, and quantification of
      intracellular compatible solutes. Second, ion-imaging with cation-specific
      fluorescent dyes was employed to analyze changes in the relative ion
      concentrations in intact cells. Third, the effect of salt concentrations on the
      catalytic performance of S. salinarum malate dehydrogenase (MDH) and isocitrate
      dehydrogenase (ICDH) was determined. 1H-NMR spectroscopy identified glycine
      betaine (GB) and ectoine (Ect) as the main compatible solutes in S. salinarum.
      Moreover, a significant positive correlation of intracellular GB and Ect
      concentrations and external salinity was observed. The addition of exogenous GB,
      Ect, and choline (Ch) stimulated the cell growth notably, indicating that S.
      salinarum accumulates the solutes from the external medium. Addition of external
      13C2-Ch resulted in conversion to 13C2-GB, indicating biosynthesis of GB from Ch.
      An increase of external salinity up to 21% did not result in an increase in
      cytoplasmic sodium concentration in S. salinarum. This, together with the
      decrease in the catalytic activities of MDH and ICDH at high salt concentration,
      demonstrates that S. salinarum employs the salt-out strategy for haloadaptation.

PMID- 29357352
TI  - Molecular detection of airborne Emergomyces africanus, a thermally dimorphic
      fungal pathogen, in Cape Town, South Africa.
AB  - Emergomyces africanus is a thermally dimorphic fungus that causes a systemic
      mycosis in immunocompromised persons in South Africa. Infection is presumed to
      follow inhalation of airborne propagules. We developed a quantitative PCR
      protocol able to detect as few as 5 Es. africanus propagules per day. Samples
      were collected in Cape Town, South Africa over 50 weeks by a Burkard spore trap
      with an alternate orifice. We detected Es. africanus in air samples from 34 days
      (10%) distributed over 11 weeks. These results suggest environmental exposure to
      airborne Es. africanus propagules occurs more commonly in endemic areas than
      previously appreciated.

PMID- 29357353
TI  - Unique properties of TCR-activated p38 are necessary for NFAT-dependent T-cell
      activation.
AB  - Nuclear factor of activated T cells (NFAT) transcription factors are required for
      induction of T-cell cytokine production and effector function. Although it is
      known that activation via the T-cell antigen receptor (TCR) results in 2 critical
      steps, calcineurin-mediated NFAT1 dephosphorylation and NFAT2 up-regulation, the
      molecular mechanisms underlying each are poorly understood. Here we find that T
      cell p38, which is activated by an alternative pathway independent of the mitogen
      activated protein (MAP) kinase cascade and with different substrate
      specificities, directly controls these events. First, alternatively (but not
      classically) activated p38 was required to induce the expression of the AP-1
      component c-Fos, which was necessary for NFAT2 expression and cytokine
      production. Second, alternatively (but not classically) activated p38
      phosphorylated NFAT1 on a heretofore unidentified site, S79, and in its absence
      NFAT1 was unable to interact with calcineurin or migrate to the nucleus. These
      results demonstrate that the acquisition of unique specificities by TCR-activated
      p38 orchestrates NFAT-dependent T-cell functions.

PMID- 29357354
TI  - Repression of branched-chain amino acid synthesis in Staphylococcus aureus is
      mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.
AB  - Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine,
      leucine, valine) for protein synthesis, branched-chain fatty acid synthesis, and
      environmental adaptation by responding to their availability via the global
      transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology
      necessitates that it either synthesize them or scavenge them from the
      environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs,
      however, its ability to synthesize them has remained conflicted by reports that
      it is auxotrophic for leucine and valine despite carrying an intact BCAA
      biosynthetic operon. In revisiting these findings, we have observed that S.
      aureus can engage in leucine and valine synthesis, but the level of BCAA
      synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize
      that each BCAA differentially regulates the biosynthetic operon. Here we show
      that two mechanisms of transcriptional repression regulate the level of
      endogenous BCAA biosynthesis in response to specific BCAA availability. We
      identify a trans-acting mechanism involving isoleucine-dependent repression by
      the global transcriptional regulator CodY and a cis-acting leucine-responsive
      attenuator, uncovering how S. aureus regulates endogenous biosynthesis in
      response to exogenous BCAA availability. Moreover, given that isoleucine can
      dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a
      global regulator of metabolism and virulence in S. aureus, we extend the
      importance of isoleucine availability for CodY-dependent regulation of other
      metabolic and virulence genes. These data resolve the previous conflicting
      observations regarding BCAA biosynthesis, and reveal the environmental signals
      that not only induce BCAA biosynthesis, but that could also have broader
      consequences on S. aureus environmental adaptation and virulence via CodY.

PMID- 29357355
TI  - The Arabidopsis SUMO E3 ligase SIZ1 mediates the temperature dependent trade-off
      between plant immunity and growth.
AB  - Increased ambient temperature is inhibitory to plant immunity including auto
      immunity. SNC1-dependent auto-immunity is, for example, fully suppressed at 28
      degrees C. We found that the Arabidopsis sumoylation mutant siz1 displays SNC1
      dependent auto-immunity at 22 degrees C but also at 28 degrees C, which was EDS1
      dependent at both temperatures. This siz1 auto-immune phenotype provided enhanced
      resistance to Pseudomonas at both temperatures. Moreover, the rosette size of
      siz1 recovered only weakly at 28 degrees C, while this temperature fully rescues
      the growth defects of other SNC1-dependent auto-immune mutants. This thermo
      insensitivity of siz1 correlated with a compromised thermosensory growth
      response, which was independent of the immune regulators PAD4 or SNC1. Our data
      reveal that this high temperature induced growth response strongly depends on
      COP1, while SIZ1 controls the amplitude of this growth response. This latter
      notion is supported by transcriptomics data, i.e. SIZ1 controls the amplitude and
      timing of high temperature transcriptional changes including a subset of the
      PIF4/BZR1 gene targets. Combined our data signify that SIZ1 suppresses an SNC1
      dependent resistance response at both normal and high temperatures. At the same
      time, SIZ1 amplifies the dark and high temperature growth response, likely via
      COP1 and upstream of gene regulation by PIF4 and BRZ1.

PMID- 29357356
TI  - Genetic variants in pachyonychia congenita-associated keratins increase
      susceptibility to tooth decay.
AB  - Pachyonychia congenita (PC) is a cutaneous disorder primarily characterized by
      nail dystrophy and painful palmoplantar keratoderma. PC is caused by mutations in
      KRT6A, KRT6B, KRT6C, KRT16, and KRT17, a set of keratin genes expressed in the
      nail bed, palmoplantar epidermis, oral mucosal epithelium, hair follicle and
      sweat gland. RNA-seq analysis revealed that all PC-associated keratins (except
      for Krt6c that does exist in the mouse genome) are expressed in the mouse enamel
      organ. We further demonstrated that these keratins are produced by ameloblasts
      and are incorporated into mature human enamel. Using genetic and intraoral
      examination data from 573 adults and 449 children, we identified several missense
      polymorphisms in KRT6A, KRT6B and KRT6C that lead to a higher risk for dental
      caries. Structural analysis of teeth from a PC patient carrying a p.Asn171Lys
      substitution in keratin-6a (K6a) revealed disruption of enamel rod sheaths
      resulting in altered rod shape and distribution. Finally, this PC-associated
      substitution as well as more frequent caries-associated SNPs, found in two of the
      KRT6 genes, that result in p.Ser143Asn substitution (rs28538343 in KRT6B and
      rs151117600 in KRT6C), alter the assembly of K6 filaments in ameloblast-like
      cells. These results identify a new set of keratins involved in tooth enamel
      formation, distinguish novel susceptibility loci for tooth decay and reveal
      additional clinical features of pachyonychia congenita.

PMID- 29357357
TI  - What drives the perceptual change resulting from speech motor adaptation?
      Evaluation of hypotheses in a Bayesian modeling framework.
AB  - Shifts in perceptual boundaries resulting from speech motor learning induced by
      perturbations of the auditory feedback were taken as evidence for the involvement
      of motor functions in auditory speech perception. Beyond this general statement,
      the precise mechanisms underlying this involvement are not yet fully understood.
      In this paper we propose a quantitative evaluation of some hypotheses concerning
      the motor and auditory updates that could result from motor learning, in the
      context of various assumptions about the roles of the auditory and somatosensory
      pathways in speech perception. This analysis was made possible thanks to the use
      of a Bayesian model that implements these hypotheses by expressing the
      relationships between speech production and speech perception in a joint
      probability distribution. The evaluation focuses on how the hypotheses can (1)
      predict the location of perceptual boundary shifts once the perturbation has been
      removed, (2) account for the magnitude of the compensation in presence of the
      perturbation, and (3) describe the correlation between these two behavioral
      characteristics. Experimental findings about changes in speech perception
      following adaptation to auditory feedback perturbations serve as reference.
      Simulations suggest that they are compatible with a framework in which motor
      adaptation updates both the auditory-motor internal model and the auditory
      characterization of the perturbed phoneme, and where perception involves both
      auditory and somatosensory pathways.

PMID- 29357358
TI  - Effects of a psychological intervention programme on mental stress, coping style
      and immune function in percutaneous coronary intervention patients.
AB  - PURPOSE: This study aimed to assess the effects of a psychological intervention
      programme on the mental stress, coping style and cortisol and IL-2 levels of
      patients undergoing percutaneous coronary intervention (PCI). METHODS: A total of
      sixty cardiovascular patients scheduled for PCI with clear anxiety and depression
      screened by the Hospital Anxiety and Depression Scale were randomly divided into
      an experimental (n = 30) and control (n = 30) group. The participants in the
      experimental group received cognitive therapy, relaxation therapy and emotional
      support. Self-reported questionnaires, including the Self-Report Symptom
      Checklist (SCL-90) and the Medical Coping Mode Questionnaire (MCMQ), and levels
      of IL-2 and cortisol were collected at baseline and the day before discharge.
      RESULTS: Compared with the controls, patients in the intervention group had a
      better mental state and coping style (confrontation), higher levels of IL-2 and
      lower levels of cortisol (all P<0.05). CONCLUSIONS: The psychological
      intervention programme effectively improved mental state, reduced negative coping
      styles, increased levels of IL-2, and decreased cortisol levels in patients
      undergoing PCI. This programme may be an effective preoperative nursing
      intervention for PCI patients. TRIAL REGISTRATION: Chinese Clinical Trail
      Registry ChiCTR-IOR-16007864.

PMID- 29357359
TI  - Compound heterozygous loss-of-function mutations in KIF20A are associated with a
      novel lethal congenital cardiomyopathy in two siblings.
AB  - Congenital or neonatal cardiomyopathies are commonly associated with a poor
      prognosis and have multiple etiologies. In two siblings, a male and female, we
      identified an undescribed type of lethal congenital restrictive cardiomyopathy
      affecting the right ventricle. We hypothesized a novel autosomal recessive
      condition. To identify the cause, we performed genetic, in vitro and in vivo
      studies. Genome-wide SNP typing and parametric linkage analysis was done in a
      recessive model to identify candidate regions. Exome sequencing analysis was done
      in unaffected and affected siblings. In the linkage regions, we selected
      candidate genes that harbor two rare variants with predicted functional effects
      in the patients and for which the unaffected sibling is either heterozygous or
      homozygous reference. We identified two compound heterozygous variants in KIF20A;
      a maternal missense variant (c.544C>T: p.R182W) and a paternal frameshift
      mutation (c.1905delT: p.S635Tfs*15). Functional studies confirmed that the R182W
      mutation creates an ATPase defective form of KIF20A which is not able to support
      efficient transport of Aurora B as part of the chromosomal passenger complex. Due
      to this, Aurora B remains trapped on chromatin in dividing cells and fails to
      translocate to the spindle midzone during cytokinesis. Translational blocking of
      KIF20A in a zebrafish model resulted in a cardiomyopathy phenotype. We identified
      a novel autosomal recessive congenital restrictive cardiomyopathy, caused by a
      near complete loss-of-function of KIF20A. This finding further illustrates the
      relationship of cytokinesis and congenital cardiomyopathy.

PMID- 29357360
TI  - Signalling crosstalk during early tumorigenesis in the absence of Polycomb
      silencing.
AB  - In response to stress and injury a coordinated activation of conserved signalling
      modules, such as JNK and JAK/STAT, is critical to trigger regenerative tissue
      restoration. While these pathways rebuild homeostasis and promote faithful organ
      recovery, it is intriguing that they also become activated in various tumour
      conditions. Therefore, it is crucial to understand how similar pathways can
      achieve context-dependent functional outputs, likely depending on cellular
      states. Compromised chromatin regulation, upon removal of the Polycomb group
      member polyhomeotic, leads to tumour formation with ectopic activation of JNK
      signalling, mediated by egr/grnd, in addition to JAK/STAT and Notch. Employing
      quantitative analyses, we show that blocking ectopic signalling impairs ph tumour
      growth. Furthermore, JAK/STAT functions in parallel to JNK, while Notch relies on
      JNK. Here, we reveal a signalling hierarchy in ph tumours that is distinct from
      the regenerative processes regulated by these pathways. Absence of ph renders a
      permissive state for expression of target genes, but our results suggest that
      both loss of repression and the presence of activators may collectively regulate
      gene expression during tumorigenesis. Further dissecting the effect of
      signalling, developmental or stress-induced factors will thus elucidate the
      regulation of physiological responses and the contribution of context-specific
      cellular states.

PMID- 29357361
TI  - Defining objective clusters for rabies virus sequences using affinity propagation
      clustering.
AB  - Rabies is caused by lyssaviruses, and is one of the oldest known zoonoses. In
      recent years, more than 21,000 nucleotide sequences of rabies viruses (RABV),
      from the prototype species rabies lyssavirus, have been deposited in public
      databases. Subsequent phylogenetic analyses in combination with metadata suggest
      geographic distributions of RABV. However, these analyses somewhat experience
      technical difficulties in defining verifiable criteria for cluster allocations in
      phylogenetic trees inviting for a more rational approach. Therefore, we applied a
      relatively new mathematical clustering algorythm named 'affinity propagation
      clustering' (AP) to propose a standardized sub-species classification utilizing
      full-genome RABV sequences. Because AP has the advantage that it is
      computationally fast and works for any meaningful measure of similarity between
      data samples, it has previously been applied successfully in bioinformatics, for
      analysis of microarray and gene expression data, however, cluster analysis of
      sequences is still in its infancy. Existing (516) and original (46) full genome
      RABV sequences were used to demonstrate the application of AP for RABV
      clustering. On a global scale, AP proposed four clusters, i.e. New World cluster,
      Arctic/Arctic-like, Cosmopolitan, and Asian as previously assigned by
      phylogenetic studies. By combining AP with established phylogenetic analyses, it
      is possible to resolve phylogenetic relationships between verifiably determined
      clusters and sequences. This workflow will be useful in confirming cluster
      distributions in a uniform transparent manner, not only for RABV, but also for
      other comparative sequence analyses.

PMID- 29357362
TI  - Large-scale reduction of tyrosine kinase activities in human monocytes stimulated
      in vitro with N. meningitidis.
AB  - N. meningitidis induces extensive gene expression changes in human monocytes,
      suggesting that complex networks of signaling pathways are activated during
      meningococcal sepsis. These effects are modulated by the anti-inflammatory
      cytokine interleukin-10 (IL-10). To further study changes in signal transduction
      suggested by mRNA data, we used kinase substrate arrays to identify composite
      kinase activities induced by lysates from a primary human monocyte model system.
      Cell lysates were prepared from monocytes treated with the following experimental
      conditions: 106 N. meningitidis/mL, 25 ng/mL IL-10, 106 N. meningitidis/mL in
      combination with 25 ng/mL IL-10, and vehicle. Lysates were subjected to kinase
      activity profiling with Tyrosine Kinase PamChip(r) arrays containing 144 kinase
      peptide substrates. In our experimental model, we were not able to detect a
      statistically significant large-scale change in ex vivo array peptide
      phosphorylation by lysates from monocytes treated for 15 minutes. Targets of the
      IL-10 anti-inflammatory response were not identified. A profound inhibition of
      array peptide phosphorylation by monocytes treated for 60 minutes was identified,
      suggesting low activity of a large number of kinases associated with different
      signaling pathways and immune cell functions, including STAT3 activity, Nf-kappaB
      and VEGF signaling, and PTEN signaling activity. The peptide representing ZBTB16,
      which was reduced in phosphorylation by lysates from all three experimental
      conditions, was in Ingenuity Pathway Analysis identified to be linked to reduced
      cytokine release and mRNA levels of tumor necrosis factor (TNF), IL-6, and
      CXCL10. Further studies should investigate changes in tyrosine kinase-mediated
      signal transduction in human immune cells, in order to evaluate the potential
      clinical application of kinome profiling in the study of systemic inflammatory
      responses to pathogens.

PMID- 29357363
TI  - Unreported cases in the 2014-2016 Ebola epidemic: Spatiotemporal variation, and
      implications for estimating transmission.
AB  - In the recent 2014-2016 Ebola epidemic in West Africa, non-hospitalized cases
      were an important component of the chain of transmission. However, non
      hospitalized cases are at increased risk of going unreported because of barriers
      to access to healthcare. Furthermore, underreporting rates may fluctuate over
      space and time, biasing estimates of disease transmission rates, which are
      important for understanding spread and planning control measures. We performed a
      retrospective analysis on community deaths during the recent Ebola epidemic in
      Sierra Leone to estimate the number of unreported non-hospitalized cases, and to
      quantify how Ebola reporting rates varied across locations and over time. We then
      tested if variation in reporting rates affected the estimates of disease
      transmission rates that were used in surveillance and response. We found
      significant variation in reporting rates among districts, and district-specific
      rates of increase in reporting over time. Correcting time series of numbers of
      cases for variable reporting rates led, in some instances, to different estimates
      of the time-varying reproduction number of the epidemic, particularly outside the
      capital. Future analyses that compare Ebola transmission rates over time and
      across locations may be improved by considering the impacts of differential
      reporting rates.

PMID- 29357364
TI  - Unraveling the novel effects of aroma from small molecules in preventing hen egg
      white lysozyme amyloid fibril formation.
AB  - This study investigated for the first time the molecular effectiveness of 'aroma'
      from three small molecules including a phenol (phenyl ethyl alcohol; PEA) and an
      aldehyde (cinnamaldehyde; Cin) both containing an aromatic ring, and a diamine
      (N,N,N,N'- Tetramethylethylenediamine; TEMED) at two different amounts (small; S
      and large; L) in preventing hen egg white lysozyme (HEWL) amyloid fibril
      formation using Thioflavin T and Nile red fluorescence assays, circular dichroism
      spectroscopy, SDS-polyacrylamide gel electrophoresis, atomic force microscopy,
      dynamic light scattering and HEWL activity test. Interestingly, the results
      revealed that (1) the aroma of PEA, identified as an active constituent of Rosa
      damascena, prevented fibril formation since PEA-L was able to trap the oligomeric
      form of HEWL in contrast to PEA-S where protofibrils but not mature fibrils were
      formed; (2) Cin, previously shown to prevent fibril formation in the liquid form,
      was also shown to do so in the aroma form by producing protofibrils and not
      mature fibrils in both Cin- L and Cin-S aroma forms and (3) the aroma of TEMED-L
      was able to retain HEWL's native structure completely and prevented both
      aggregation and fibril formation, while TEMED-S prevented HEWL fibril formation
      and instead directed the pathway towards amorphous aggregate formation.
      Furthermore, the ability to trap oligomeric species (by PEA-L aroma) is of great
      importance for further research as it provides routes for preventing the
      formation of toxic oligomeric intermediates along the fibrillation pathway. Last
      but not least, the novelty of this in vitro study on the effect of aroma at the
      molecular level with a unique experimental set-up using HEWL as a model protein
      in assessing amyloid fibril formation paves the way for more and detailed studies
      on the importance of aroma producing molecules and their effects.

PMID- 29357365
TI  - Sanitation and water supply coverage thresholds associated with active trachoma:
      Modeling cross-sectional data from 13 countries.
AB  - BACKGROUND: Facial cleanliness and sanitation are postulated to reduce trachoma
      transmission, but there are no previous data on community-level herd protection
      thresholds. We characterize associations between active trachoma, access to
      improved sanitation facilities, and access to improved water sources for the
      purpose of face washing, with the aim of estimating community-level or herd
      protection thresholds. METHODS AND FINDINGS: We used cluster-sampled Global
      Trachoma Mapping Project data on 884,850 children aged 1-9 years from 354,990
      households in 13 countries. We employed multivariable mixed-effects modified
      Poisson regression models to assess the relationships between water and
      sanitation coverage and trachomatous inflammation-follicular (TF). We observed
      lower TF prevalence among those with household-level access to improved
      sanitation (prevalence ratio, PR = 0.87; 95%CI: 0.83-0.91), and household-level
      access to an improved washing water source in the residence/yard (PR = 0.81;
      95%CI: 0.75-0.88). Controlling for household-level water and latrine access, we
      found evidence of community-level protection against TF for children living in
      communities with high sanitation coverage (PR80-90% = 0.87; 95%CI: 0.73-1.02;
      PR90-100% = 0.76; 95%CI: 0.67-0.85). Community sanitation coverage levels greater
      than 80% were associated with herd protection against TF (PR = 0.77; 95%CI: 0.62
      0.97)-that is, lower TF in individuals whose households lacked individual
      sanitation but who lived in communities with high sanitation coverage. For
      community-level water coverage, there was no apparent threshold, although we
      observed lower TF among several of the higher deciles of community-level water
      coverage. CONCLUSIONS: Our study provides insights into the community water and
      sanitation coverage levels that might be required to best control trachoma. Our
      results suggest access to adequate water and sanitation can be important
      components in working towards the 2020 target of eliminating trachoma as a public
      health problem.

PMID- 29357366
TI  - MAIT cells are activated in acute Dengue virus infection and after in vitro Zika
      virus infection.
AB  - Dengue virus (DENV) and Zika virus (ZIKV) are members of the Flaviviridae and are
      predominantly transmitted via mosquito bites. Both viruses are responsible for a
      growing number of infections in tropical and subtropical regions. DENV infection
      can cause lethargy with severe morbidity and dengue shock syndrome leading to
      death in some cases. ZIKV is now linked with Guillain-Barre syndrome and fetal
      malformations including microcephaly and developmental disorders (congenital Zika
      syndrome). The protective and pathogenic roles played by the immune response in
      these infections is unknown. Mucosal-associated invariant T (MAIT) cells are a
      population of innate T cells with potent anti-bacterial activity. MAIT cells have
      also been postulated to play a role in the immune response to viral infections.
      In this study, we evaluated MAIT cell frequency, phenotype, and function in
      samples from subjects with acute and convalescent DENV infection. We found that
      in acute DENV infection, MAIT cells had elevated co-expression of the activation
      markers CD38 and HLA-DR and had a poor IFNgamma response following bacterial
      stimulation. Furthermore, we found that MAIT cells can produce IFNgamma in
      response to in vitro infection with ZIKV. This MAIT cell response was independent
      of MR1, but dependent on IL-12 and IL-18. Our results suggest that MAIT cells may
      play an important role in the immune response to Flavivirus infections.

PMID- 29357367
TI  - Genetic diversity, breed composition and admixture of Kenyan domestic pigs.
AB  - The genetic diversity of African pigs, whether domestic or wild has not been
      widely studied and there is very limited published information available.
      Available data suggests that African domestic pigs originate from different
      domestication centers as opposed to international commercial breeds. We evaluated
      two domestic pig populations in Western Kenya, in order to characterize the
      genetic diversity, breed composition and admixture of the pigs in an area known
      to be endemic for African swine fever (ASF). One of the reasons for
      characterizing these specific populations is the fact that a proportion of
      indigenous pigs have tested ASF virus (ASFv) positive but do not present with
      clinical symptoms of disease indicating some form of tolerance to infection. Pigs
      were genotyped using either the porcine SNP60 or SNP80 chip. Village pigs were
      sourced from Busia and Homabay counties in Kenya. Because bush pigs
      (Potamochoerus larvatus) and warthogs (Phacochoerus spp.) are known to be
      tolerant to ASFv infection (exhibiting no clinical symptoms despite infection),
      they were included in the study to assess whether domestic pigs have similar
      genomic signatures. Additionally, samples representing European wild boar and
      international commercial breeds were included as references, given their
      potential contribution to the genetic make-up of the target domestic populations.
      The data indicate that village pigs in Busia are a non-homogenous admixed
      population with significant introgression of genes from international commercial
      breeds. Pigs from Homabay by contrast, represent a homogenous population with a
      "local indigenous' composition that is distinct from the international breeds,
      and clusters more closely with the European wild boar than African wild pigs.
      Interestingly, village pigs from Busia that tested negative by PCR for ASFv
      genotype IX, had significantly higher local ancestry (>54%) compared to those
      testing positive, which contained more commercial breed gene introgression. This
      may have implication for breed selection and utilization in ASF endemic areas. A
      genome wide scan detected several regions under preferential selection with
      signatures for pigs from Busia and Homabay being very distinct. Additionally,
      there was no similarity in specific genes under selection between the wild pigs
      and domestic pigs despite having some broad areas under similar selection
      signatures. These results provide a basis to explore possible genetic
      determinants underlying tolerance to infection by ASFv genotypes and suggests
      multiple pathways for genetically mediated ASFv tolerance given the diversity of
      selection signatures observed among the populations studied.

PMID- 29357368
TI  - Serum apolipoprotein E may be a novel biomarker of migraine.
AB  - Migraine attacks alter various molecules that might be related to the
      pathophysiology of migraine, such as serotonin, calcitonin gene-related peptide,
      and nitric oxide. The underlying pathophysiology of migraine is as yet unclear.
      We explored key proteins related to the pathogenesis of migraine here. Serum was
      collected from two patients with migraine with aura (MA) and seven patients with
      migraine without aura (MO) during attack-free periods and migraine attacks.
      Samples were analyzed using 2-dimensional gel electrophoresis. Nineteen protein
      spots were altered between the attack-free versus migraine attack periods. Mass
      spectrometric analysis was performed to identify the proteins within each of the
      19 altered spots. Thirty-six proteins were significantly altered in samples
      collected during attack-free periods versus migraine attacks. The protein with
      the statistically most significant MASCOT/Mowse score (268+/-112) among
      lipoproteins was apolipoprotein (ApoE). In the MA and MO groups, ApoE protein
      levels were significantly higher during migraine attack than during the attack
      free period (p<0.05). ApoE protein levels were also significantly increased in
      the MA group during the attack-free period compared to healthy controls and
      patients with tension type headaches (p<0.01). Migraine alters ApoE levels,
      especially in MA. ApoE might play an important role in the pathophysiology of
      migraine, and may act as a diagnostic biomarker of migraine.

PMID- 29357369
TI  - Relationship between QTL for grain shape, grain weight, test weight, milling
      yield, and plant height in the spring wheat cross RL4452/'AC Domain'.
AB  - Kernel morphology characteristics of wheat are complex and quantitatively
      inherited. A doubled haploid (DH) population of the cross RL4452/'AC Domain' was
      used to study the genetic basis of seed shape. Quantitative trait loci (QTL)
      analyses were conducted on a total of 18 traits: 14 grain shape traits, flour
      yield (Fyd), and three agronomic traits (Plant height [Plht], 1000 Grain weight
      [Gwt], Test weight [Twt]), using data from trial locations at Glenlea, Brandon,
      and Morden in Manitoba, Canada, between 1999 and 2004. Kernel shape was studied
      through digital image analysis with an Acurum(r) grain analyzer. Plht, Gwt, Twt,
      Fyd, and grain shape QTL were correlated with each other and QTL analysis
      revealed that QTL for these traits often mapped to the same genetic locations.
      The most significant QTL for the grain shape traits were located on chromosomes
      4B and 4D, each accounting for up to 24.4% and 53.3% of the total phenotypic
      variation, respectively. In addition, the most significant QTL for Plht, Gwt, and
      Twt were all detected on chromosome 4D at the Rht-D1 locus. Rht-D1b decreased
      Plht, Gwt, Twt, and kernel width relative to the Rht-D1a allele. A narrow genetic
      interval on chromosome 4B contained significant QTL for grain shape, Gwt, and
      Plht. The 'AC Domain' allele reduced Plht, Gwt, kernel length and width traits,
      but had no detectable effect on Twt. The data indicated that this variation was
      inconsistent with segregation at Rht-B1. Numerous QTL were identified that
      control these traits in this population.

PMID- 29357370
TI  - Parallel PI3K, AKT and mTOR inhibition is required to control feedback loops that
      limit tumor therapy.
AB  - Targeting the PI3K pathway has achieved limited success in cancer therapy. One
      reason for the disappointing activity of drugs that interfere with molecules that
      are important player in this pathway is the induction of multiple feedback loops
      that have been only partially understood. To understand these limitations and
      develop improved treatment strategies, we comprehensively characterized molecular
      mechanisms of PI3K pathway signaling in bladder cancer cell lines upon using
      small molecule inhibitors and RNAi technologies against all key molecules and
      protein complexes within the pathway and analyzed functional and molecular
      consequences. When targeting either mTORC1, mTOR, AKT or PI3K, only S6K1
      phosphorylation was affected in most cell lines examined. Dephosphorylation of 4E
      BP1 required combined inhibition of PI3K and mTORC1, independent from AKT, and
      resulted in a robust reduction in cell viability. Long-term inhibition of PI3K
      however resulted in a PDK1-dependent, PIP3 and mTORC2 independent
      rephosphorylation of AKT. AKT rephosphorylation could also be induced by mTOR or
      PDK1 inhibition. Combining PI3K/mTOR inhibitors with AKT or PDK1 inhibitors
      suppressed this rephosphorylation, induced apoptosis, decreased colony formation,
      cell viability and growth of tumor xenografts. Our findings reveal novel
      molecular mechanisms that explain the requirement for simultaneous targeting of
      PI3K, AKT and mTORC1 to achieve effective tumor growth inhibition.

PMID- 29357371
TI  - Evaluating the impact of fast-fMRI on dynamic functional connectivity in an event
      based paradigm.
AB  - The human brain is known to contain several functional networks that interact
      dynamically. Therefore, it is desirable to analyze the temporal features of these
      networks by dynamic functional connectivity (dFC). A sliding window approach was
      used in an event-related fMRI (visual stimulation using checkerboards) to assess
      the impact of repetition time (TR) and window size on the temporal features of
      BOLD dFC. In addition, we also examined the spatial distribution of dFC and
      tested the feasibility of this approach for the analysis of interictal
      epileptiforme discharges. 15 healthy controls (visual stimulation paradigm) and
      three patients with epilepsy (EEG-fMRI) were measured with EPI-fMRI. We
      calculated the functional connectivity degree (FCD) by determining the total
      number of connections of a given voxel above a predefined threshold based on
      Pearson correlation. FCD could capture hemodynamic changes relative to stimulus
      onset in controls. A significant effect of TR and window size was observed on FCD
      estimates. At a conventional TR of 2.6 s, FCD values were marginal compared to
      FCD values using sub-seconds TRs achievable with multiband (MB) fMRI. Concerning
      window sizes, a specific maximum of FCD values (inverted u-shape behavior) was
      found for each TR, indicating a limit to the possible gain in FCD for increasing
      window size. In patients, a dynamic FCD change was found relative to the onset of
      epileptiform EEG patterns, which was compatible with their clinical semiology.
      Our findings indicate that dynamic FCD transients are better detectable with sub
      second TR than conventional TR. This approach was capable of capturing neuronal
      connectivity across various regions of the brain, indicating a potential to study
      the temporal characteristics of interictal epileptiform discharges and seizures
      in epilepsy patients or other brain diseases with brief events.

PMID- 29357372
TI  - Inhibitors of Trypanosoma cruzi Sir2 related protein 1 as potential drugs against
      Chagas disease.
AB  - Chagas disease remains one of the most neglected diseases in the world despite
      being the most important parasitic disease in Latin America. The characteristic
      chronic manifestation of chagasic cardiomyopathy is the region's leading cause of
      heart-related illness, causing significant mortality and morbidity. Due to the
      limited available therapeutic options, new drugs are urgently needed to control
      the disease. Sirtuins, also called Silent information regulator 2 (Sir2) proteins
      have long been suggested as interesting targets to treat different diseases,
      including parasitic infections. Recent studies on Trypanosoma cruzi sirtuins have
      hinted at the possibility to exploit these enzymes as a possible drug targets. In
      the present work, the T. cruzi Sir2 related protein 1 (TcSir2rp1) is genetically
      validated as a drug target and biochemically characterized for its NAD+-dependent
      deacetylase activity and its inhibition by the classic sirtuin inhibitor
      nicotinamide, as well as by bisnaphthalimidopropyl (BNIP) derivatives, a class of
      parasite sirtuin inhibitors. BNIPs ability to inhibit TcSir2rp1, and anti
      parasitic activity against T. cruzi amastigotes in vitro were investigated. The
      compound BNIP Spermidine (BNIPSpd) (9), was found to be the most potent inhibitor
      of TcSir2rp1. Moreover, this compound showed altered trypanocidal activity
      against TcSir2rp1 overexpressing epimastigotes and anti-parasitic activity
      similar to the reference drug benznidazole against the medically important
      amastigotes, while having the highest selectivity index amongst the compounds
      tested. Unfortunately, BNIPSpd failed to treat a mouse model of Chagas disease,
      possibly due to its pharmacokinetic profile. Medicinal chemistry modifications of
      the compound, as well as alternative formulations may improve activity and
      pharmacokinetics in the future. Additionally, an initial TcSIR2rp1 model in
      complex with p53 peptide substrate was obtained from low resolution X-ray data
      (3.5 A) to gain insight into the potential specificity of the interaction with
      the BNIP compounds. In conclusion, the search for TcSir2rp1 specific inhibitors
      may represent a valuable strategy for drug discovery against T. cruzi.

PMID- 29357374
TI  - Global estimation of areas with suitable environmental conditions for mariculture
      species.
AB  - Aquaculture has grown rapidly over the last three decades expanding at an average
      annual growth rate of 5.8% (2005-2014), down from 8.8% achieved between 1980 and
      2010. The sector now produces 44% of total food fish production. Increasing
      demand and consumption from a growing global population are driving further
      expansion of both inland and marine aquaculture (i.e., mariculture, including
      marine species farmed on land). However, the growth of mariculture is dependent
      on the availability of suitable farming areas for new facilities, particularly
      for open farming practices that rely on the natural oceanic environmental
      parameters such as temperature, oxygen, chlorophyll etc. In this study, we
      estimated the marine areas within the exclusive economic zones of all countries
      that were suitable for potential open ocean mariculture activities. To this end,
      we quantify the environmental niche and inferred the global habitat suitability
      index (HSI) of the 102 most farmed marine species using four species distribution
      models. The average weighted HSI across the four models suggests that 72,000,000
      km2 of ocean are to be environmentally suitable to farm one or more species.
      About 92% of the predicted area (66,000,000 km2) is environmentally suitable for
      farming finfish, 43% (31,000,000 km2) for molluscs and 54% (39,000,000 km2) for
      crustaceans. These predictions do not consider technological feasibility that can
      limit crustaceans farming in open waters. Suitable mariculture areas along the
      Atlantic coast of South America and West Africa appear to be most under-utilized
      for farming. Our results suggest that factors other than environmental
      considerations such as the lack of socio-economic and technological capacity, as
      well as aqua feed supply are currently limiting the potential for mariculture
      expansion in many areas.

PMID- 29357373
TI  - Internal and external cooling methods and their effect on body temperature,
      thermal perception and dexterity.
AB  - OBJECTIVE: The present study aimed to compare a range of cooling methods possibly
      utilised by occupational workers, focusing on their effect on body temperature,
      perception and manual dexterity. METHODS: Ten male participants completed eight
      trials involving 30 min of seated rest followed by 30 min of cooling or control
      of no cooling (CON) (34 degrees C, 58% relative humidity). The cooling methods
      utilised were: ice cooling vest (CV0), phase change cooling vest melting at 14
      degrees C (CV14), evaporative cooling vest (CVEV), arm immersion in 10 degrees C
      water (AI), portable water-perfused suit (WPS), heliox inhalation (HE) and ice
      slushy ingestion (SL). Immediately before and after cooling, participants were
      assessed for fine (Purdue pegboard task) and gross (grip and pinch strength)
      manual dexterity. Rectal and skin temperature, as well as thermal sensation and
      comfort, were monitored throughout. RESULTS: Compared with CON, SL was the only
      method to reduce rectal temperature (P = 0.012). All externally applied cooling
      methods reduced skin temperature (P<0.05), though CV0 resulted in the lowest skin
      temperature versus other cooling methods. Participants felt cooler with CV0,
      CV14, WPS, AI and SL (P<0.05). AI significantly impaired Purdue pegboard
      performance (P = 0.001), but did not affect grip or pinch strength (P>0.05).
      CONCLUSION: The present study observed that ice ingestion or ice applied to the
      skin produced the greatest effect on rectal and skin temperature, respectively.
      AI should not be utilised if workers require subsequent fine manual dexterity.
      These results will help inform future studies investigating appropriate pre
      cooling methods for the occupational worker.

PMID- 29357376
TI  - Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1
      Bi-2, induce potent cancer cell killing in muc1 positive tumor cells.
AB  - Muc1 is one of the most studied tumor antigens. However, antibodies or antibody
      toxin conjugates against Muc1 have not shown significant efficacy for tumors with
      Muc1 overexpression. In this study, we employed bispecific antibody approach to
      target Muc1 positive tumor cells. A novel bispecific antibody, Muc1-Bi-1, was
      constructed by linking single domain antibodies, anti-Muc1-VHH and anti-CD16-VHH.
      Muc1-Bi-2, the humanized form of Muc1-Bi-1, was also constructed by grafting.
      Both Muc1-Bi bispecific antibodies can be efficiently expressed and purified from
      bacteria. In vitro, the Muc1-Bi bispecific antibodies can recruit Natural Killer
      (NK) cells to drive potent and specific cell killing of Muc1-overexpressing tumor
      cells. In xenograft model, the Muc1-Bi bispecific antibodies can suppress tumor
      growth in the presence of human peripheral blood mononuclear cells (PBMC). These
      data suggested that the single domain based Muc1-Bi may provide a valid strategy
      for targeting tumors with Muc1 overexpression.

PMID- 29357375
TI  - Identification of a novel protein complex essential for effector translocation
      across the parasitophorous vacuole membrane of Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular parasite that can infect virtually
      all nucleated cells in warm-blooded animals. The ability of Toxoplasma
      tachyzoites to infect and successfully manipulate its host is dependent on its
      ability to transport "GRA" proteins that originate in unique secretory organelles
      called dense granules into the host cell in which they reside. GRAs have diverse
      roles in Toxoplasma's intracellular lifecycle, including co-opting crucial host
      cell functions and proteins, such as the cell cycle, c-Myc and p38 MAP kinase.
      Some of these GRA proteins, such as GRA16 and GRA24, are secreted into the
      parasitophorous vacuole (PV) within which Toxoplasma replicates and are
      transported across the PV membrane (PVM) into the host cell, but the
      translocation process and its machinery are not well understood. We previously
      showed that TgMYR1, which is cleaved by TgASP5 into two fragments, localizes to
      the PVM and is essential for GRA transport into the host cell. To identify
      additional proteins necessary for effector transport, we screened Toxoplasma
      mutants defective in c-Myc up-regulation for their ability to export GRA16 and
      GRA24 to the host cell nucleus. Here we report that novel proteins MYR2 and MYR3
      play a crucial role in translocation of a subset of GRAs into the host cell. MYR2
      and MYR3 are secreted into the PV space and co-localize with PV membranes and
      MYR1. Consistent with their predicted transmembrane domains, all three proteins
      are membrane-associated, and MYR3, but not MYR2, stably associates with MYR1,
      whose N- and C-terminal fragments are disulfide-linked. We further show that
      fusing intrinsically disordered effectors to a structured DHFR domain blocks the
      transport of other effectors, consistent with a translocon-based model of
      effector transport. Overall, these results reveal a novel complex at the PVM that
      is essential for effector translocation into the host cell.

PMID- 29357378
TI  - Low cost automated whole smear microscopy screening system for detection of acid
      fast bacilli.
AB  - BACKGROUND: In countries with high tuberculosis (TB) burden, there is urgent need
      for rapid, large-scale screening to detect smear-positive patients. We developed
      a computer-aided whole smear screening system that focuses in real-time, captures
      images and provides diagnostic grading, for both bright-field and fluorescence
      microscopy for detection of acid-fast-bacilli (AFB) from respiratory specimens.
      OBJECTIVES: To evaluate the performance of dual-mode screening system in AFB
      diagnostic algorithms on concentrated smears with auramine O (AO) staining, as
      well as direct smears with AO and Ziehl-Neelsen (ZN) staining, using
      mycobacterial culture results as gold standard. METHODS: Adult patient sputum
      samples requesting for M. tuberculosis cultures were divided into three batches
      for staining: direct AO-stained, direct ZN-stained and concentrated smears AO
      stained. All slides were graded by an experienced microscopist, in parallel with
      the automated whole smear screening system. Sensitivity and specificity of a TB
      diagnostic algorithm in using the screening system alone, and in combination with
      a microscopist, were evaluated. RESULTS: Of 488 direct AO-stained smears, 228
      were culture positive. These yielded a sensitivity of 81.6% and specificity of
      74.2%. Of 334 direct smears with ZN staining, 142 were culture positive, which
      gave a sensitivity of 70.4% and specificity of 76.6%. Of 505 concentrated smears
      with AO staining, 250 were culture positive, giving a sensitivity of 86.4% and
      specificity of 71.0%. To further improve performance, machine grading was
      confirmed by manual smear grading when the number of AFBs detected fell within an
      uncertainty range. These combined results gave significant improvement in
      specificity (AO-direct:85.4%; ZN-direct:85.4%; AO-concentrated:92.5%) and slight
      improvement in sensitivity while requiring only limited manual workload.
      CONCLUSION: Our system achieved high sensitivity without substantially
      compromising specificity when compared to culture results. Significant
      improvement in specificity was obtained when uncertain results were confirmed by
      manual smear grading. This approach had potential to substantially reduce
      workload of microscopists in high burden countries.

PMID- 29357377
TI  - A systematic review of regulatory and educational interventions to reduce the
      burden associated with the prescriptions of sedative-hypnotics in adults treated
      for sleep disorders.
AB  - BACKGROUND: The burden of Sedative-Hypnotics (SHs) has been known since the
      1980s. Yet, their consumption remains high. A systematic review of the literature
      should help to assess efficient interventions to improve the appropriate use of
      SHs in sleep disorders. OBJECTIVES: To identify and assess regulatory and
      educational interventions designed to improve the appropriate use of SHs for
      insomnia treatment. METHODS: We conducted a systematic review of the literature
      according to PRISMA guidelines. A systematic search covering the period 1980-2015
      was carried out in Medline, Web of Science, Embase and PsycInfo. We included
      studies reporting the implementation of regulatory or educational strategies
      directed towards patients and/or healthcare professionals to improve the
      appropriate use of SHs to treat insomnia in the community, hospitals and nursing
      homes. RESULTS: Thirty-one studies were included: 23 assessed educational
      interventions (recommendations by mail/email, computer alerts, meetings, mass
      media campaigns, prescription profile), 8 assessed regulatory interventions
      (prescription rule restriction, end of reimbursement). The most recent was
      implemented in 2009. Restrictive prescription rules were effective to reduce the
      consumption of targeted SHs but led to a switch to other non-recommended SHs.
      Among educational interventions, only 3 studies out of 7 reported positive
      results of mono-faceted interventions; whereas, 13 out of the 16 multi-faceted
      interventions were reported as efficient: particularly, the active involvement of
      healthcare professionals and patients and the spread of information through mass
      media were successful. The risk of bias was high for 24 studies (mainly due to
      the design), moderate for 3 studies and weak for 4 studies. CONCLUSION:
      Educational multifaceted studies are presented as the most efficient. But further
      better designed studies are needed to make evidence-based results more
      generalizable.

PMID- 29357381
TI  - Influence of tow duration on catch performance of trawl survey in the
      Mediterranean Sea.
AB  - The aim of this study was to assess the effect of tow duration on catch per unit
      of swept area (CPUE), trawl catch performance, and the proportion of the species
      caught in a trawl survey. Longer tows are expected to have a greater probability
      of catching species. An average of 26 species were caught in the first 30
      minutes, whereas only about one additional species was caught in the next 30
      minutes in longer tows. The shorter tows involved a decrement in catch weight for
      11 of the 12 target species sampled, demonstrating that tow duration did affect
      catch per unit of swept area CPUE. The shorter tows were associated with a
      significant reduction of the overall CPUE in terms of weight of the main target
      species and of the total catch (circa 60%). The same strong reduction of around
      70% was found in particular for European hake (Merluccius merluccius) and
      surmullet (Mullus spp) and 50% for Nephrops (Nephrops norvegicus). The shorter
      tows were less efficient in catching large-sized hake, surmullet, Nephrops,
      Atlantic horse mackerel (Trachurus trachurus), and poor cod (Trisopterus
      minutus), even though the difference was significant only for Nephrops.
      Regardless of the p-value statistic, these findings suggest that the continuity
      of survey time series would be severely impaired by changing tow duration.
      Further work is required to explore a way to reduce tow duration without reducing
      CPUE.

PMID- 29357379
TI  - Impact of chronic exposure to the pesticide chlorpyrifos on respiratory
      parameters and sleep apnea in juvenile and adult rats.
AB  - The widely used organophosphorus pesticide chlorpyrifos (CPF) is often detected
      in food. CPF inhibits acetylcholinesterase and can modify muscle contractility
      and respiratory patterns. We studied the effects of chronic exposure to CPF on
      respiratory parameters and diaphragm contractility in 21- and 60-days old rats.
      Pregnant rats were exposed to oral CPF (1 or 5 mg/ kg /day: CPF-1 or CPF-5 groups
      vs vehicle: controls) from gestation onset up to weaning of the pups that were
      individually gavaged (CPF or vehicle) thereafter. Two developmental time points
      were studied: weaning (day 21) and adulthood (day 60). Whole-body plethysmography
      was used to score breathing patterns and apnea index during sleep. Then,
      diaphragm strips were dissected for the assessment of contractility and
      acetylcholinesterase activity. Results showed that the sleep apnea index was
      higher in CPF-exposed rats than in controls. In adult rats, the expiratory time
      and tidal volume were higher in CPF-exposed animals than in controls. At both
      ages, the diaphragm's amplitude of contraction and fatigability index were higher
      in the CPF-5 group, due to lower acetylcholinesterase activity. We conclude that
      chronic exposure to CPF is associated with higher sleep apnea index and diaphragm
      contractility, and modifies respiratory patterns in sleeping juvenile and adult
      rats.

PMID- 29357380
TI  - Structured peer-led diabetes self-management and support in a low-income country:
      The ST2EP randomised controlled trial in Mali.
AB  - OBJECTIVES: Our objective was to evaluate the effectiveness of peer-led self
      management education in improving glycaemic control in patients with type 2
      diabetes in a low-income country (Mali). METHODS: We conducted an open-label
      randomised controlled trial. A total of 151 adults (76% women, mean age 52.5)
      with type 2 diabetes (HbA1c>=8%), treated in the diabetes consultation units of
      two secondary health centres in Bamako, were allocated to peer-led structured
      patient education (n = 76) or conventional care alone (n = 75). The intervention
      group received 1 year of culturally tailored structured patient education (3
      courses of 4 sessions) delivered in the community by five trained peer educators.
      Both groups underwent conventional diabetes monitoring and follow-up. Primary
      outcome was the mean absolute change in HbA1c from baseline to 12 months.
      RESULTS: 177 education sessions were delivered to the intervention group. Patient
      attrition was 8%. From baseline to 12 months, the decrease in HbA1c levels was
      1.05% (SD = 2.0; CI95%: 1.54;-0.56) in the intervention group compared with 0.15%
      (SD = 1.7; CI95%: -0.56; 0.26) in the control group, p = 0.006. Mean BMI change
      was -1.65 kg/m2 (SD = 2.5; CI95%: -2.25; -1.06) in the intervention group and
      +0.05 kg/m2 (SD = 3.2; CI95%: -0.71; 0.81) in the control group, p = 0.0005. Mean
      waist circumference decreased by 3.34 cm (SD = 9.3; CI95%: -5.56;-1.13) in the
      intervention group and increased by 2.65 cm (SD = 10.3; CI95%: 0.20; 5.09) in the
      control group, p = 0.0003. CONCLUSIONS: Peer-led structured patient education
      delivered over 1 year to patients with poorly controlled type 2 diabetes in Mali
      yielded substantial improvements in glycaemic control and anthropometric
      parameters. This is of importance for the scaling up of efficient interventions
      in low-resource settings in the future. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01485913.

PMID- 29357382
TI  - Environmental DNA (eDNA): A tool for quantifying the abundant but elusive round
      goby (Neogobius melanostomus).
AB  - Environmental DNA (eDNA) is revolutionizing biodiversity monitoring, occupancy
      estimates, and real-time detections of invasive species. In the Great Lakes, the
      round goby (Neogobius melanostomus), an invasive benthic fish from the Black Sea,
      has spread to encompass all five lakes and many tributaries, outcompeting or
      consuming native species; however, estimates of round goby abundance are
      confounded by behavior and habitat preference, which impact reliable methods for
      estimating their population. By integrating eDNA into round goby monitoring,
      improved estimates of biomass may be obtainable. We conducted mesocosm
      experiments to estimate rates of goby DNA shedding and decay. Further, we
      compared eDNA with several methods of traditional field sampling to compare its
      use as an alternative/complementary monitoring method. Environmental DNA decay
      was comparable to other fish species, and first-order decay was lower at 12
      degrees C (k = 0.043) than at 19 degrees C (k = 0.058). Round goby eDNA was
      routinely detected in known invaded sites of Lake Michigan and its tributaries
      (range log10 4.8-6.2 CN/L), but not upstream of an artificial fish barrier.
      Traditional techniques (mark-recapture, seining, trapping) in Lakes Michigan and
      Huron resulted in fewer, more variable detections than eDNA, but trapping and
      eDNA were correlated (Pearson R = 0.87). Additional field testing will help
      correlate round goby abundance with eDNA, providing insight on its role as a prey
      fish and its impact on food webs.

PMID- 29357383
TI  - The relation between household income and surgical outcome in the Dutch setting
      of equal access to and provision of healthcare.
AB  - BACKGROUND: The impact of socioeconomic disparities on surgical outcome in the
      absence of healthcare inequality remains unclear. Therefore, we set out to
      determine the association between socioeconomic status (SES), reflected by
      household income, and overall survival after surgery in the Dutch setting of
      equal access and provision of care. Additionally, we aim to assess whether SES is
      associated with cause-specific survival and major 30-day complications. METHODS:
      Patients undergoing surgery between March 2005 and December 2006 in a general
      teaching hospital in the Netherlands were prospectively included. Adjusted
      logistic and cox regression analyses were used to assess the independent
      association of SES-quantified by gross household income-with major 30-day
      complications and long-term postoperative survival. RESULTS: A total of 3929
      patients were included, with a median follow-up of 6.3 years. Low household
      income was associated with worse survival in continuous analysis (HR: 1.05 per
      10.000 euro decrease in income, 95% CI: 1.01-1.10) and in income quartile
      analysis (HR: 1.58, 95% CI: 1.08-2.31, first [i.e. lowest] quartile relative to
      the fourth quartile). Similarly, low income patients were at higher risk of
      cardiovascular death (HR: 1.26 per 10.000 decrease in income, 95% CI: 1.07-1.48,
      first income quartile: HR: 3.10, 95% CI: 1.04-9.22). Household income was not
      independently associated with cancer-related mortality and major 30-day
      complications. CONCLUSIONS: Low SES, quantified by gross household income, is
      associated with increased overall and cardiovascular mortality risks among
      surgical patients. Considering the equality of care provided by this study
      setting, the associated survival hazards can be attributed to patient and
      provider factors, rather than disparities in healthcare. Increased physician
      awareness of SES as a risk factor in preoperative decision-making and focus on
      improving established SES-related risk factors may improve surgical outcome of
      low SES patients.

PMID- 29357385
TI  - Infectious blood source alters early foregut infection and regurgitative
      transmission of Yersinia pestis by rodent fleas.
AB  - Fleas can transmit Yersinia pestis by two mechanisms, early-phase transmission
      (EPT) and biofilm-dependent transmission (BDT). Transmission efficiency varies
      among flea species and the results from different studies have not always been
      consistent. One complicating variable is the species of rodent blood used for the
      infectious blood meal. To gain insight into the mechanism of EPT and the effect
      that host blood has on it, fleas were fed bacteremic mouse, rat, guinea pig, or
      gerbil blood; and the location and characteristics of the infection in the
      digestive tract and transmissibility of Y. pestis were assessed 1 to 3 days after
      infection. Surprisingly, 10-28% of two rodent flea species fed bacteremic rat or
      guinea pig blood refluxed a portion of the infected blood meal into the esophagus
      within 24 h of feeding. We term this phenomenon post-infection esophageal reflux
      (PIER). In contrast, PIER was rarely observed in rodent fleas fed bacteremic
      mouse or gerbil blood. PIER correlated with the accumulation of a dense mixed
      aggregate of Y. pestis, red blood cell stroma, and oxyhemoglobin crystals that
      filled the proventriculus. At their next feeding, fleas with PIER were 3-25 times
      more likely to appear partially blocked, with fresh blood retained within the
      esophagus, than were fleas without PIER. Three days after feeding on bacteremic
      rat blood, groups of Oropsylla montana transmitted significantly more CFU than
      did groups infected using mouse blood, and this enhanced transmission was biofilm
      dependent. Our data support a model in which EPT results from regurgitation of Y.
      pestis from a partially obstructed flea foregut and that EPT and BDT can
      sometimes temporally overlap. The relative insolubility of the hemoglobin of rats
      and Sciurids and the slower digestion of their blood appears to promote
      regurgitative transmission, which may be one reason why these rodents are
      particularly prominent in plague ecology.

PMID- 29357386
TI  - Time-course evaluation of intestinal structural disorders in a porcine model of
      intra-abdominal hypertension by mechanical intestinal obstruction.
AB  - BACKGROUND: A mechanical intestinal obstruction (MIO) can generate intraabdominal
      hypertension (IAH) that is life threatening. The intestines are very sensitive to
      IAH since the low splanchnic perfusion causes intestinal hypoxia, local acidosis
      and bacterial translocations. This may lead to acute intestinal distress syndrome
      (AIDS). The identification of intestinal injuries during IAH and its correlation
      with clinical parameters as the abdominal perfusion pressure (APP), the gastric
      intramucosal pH (pHi) and lactic acid (Lc) are still unknown. This study aimed to
      evaluate the sequence of intestinal histopathological findings in an MIO model
      and to analyze potential relationships with parameters currently used in clinical
      practice (APP, pHi and Lc). MATERIAL AND METHODS: Twenty pigs were divided into
      three groups: a control group (n = 5) and two experimental groups with 20 mmHg
      (G1, n = 10) and 30 mmHg (G2, n = 5) of IAH by MIO. The pressures were maintained
      for 3 hours, except in 5 animals in G1 where it was maintained for 5 hours. The
      APP, pHi and LA were recorded and biopsies of the terminal ileum were taken every
      30 minutes in all groups. The intestinal damage was graded according to the Park
      Score. RESULTS: Intestinal injuries were found in 42.9% of pigs in the
      experimental groups. The lesions were independent of the level and duration of
      IAH. Although APP and pHi were slightly lower in injured animals (I +) of G1 and
      G2, there were no significant differences among those uninjured (I-). Lc was
      significantly increased in all I+ pigs from the onset of IAH. CONCLUSION: The IAH
      by MIO causes intestinal lesions from the first 30 minutes with concurrent
      decreases in APP and pHi and increases in Lc. Lc could be the best clinical
      parameter related to intestinal damages with a clear difference between I + and I
      animals.

PMID- 29357384
TI  - Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob
      disease are accompanied by alterations in miRNA silencing machinery and
      biogenesis.
AB  - Increasing evidence indicates that microRNAs (miRNAs) are contributing factors to
      neurodegeneration. Alterations in miRNA signatures have been reported in several
      neurodegenerative dementias, but data in prion diseases are restricted to ex vivo
      and animal models. The present study identified significant miRNA expression
      pattern alterations in the frontal cortex and cerebellum of sporadic Creutzfeldt
      Jakob disease (sCJD) patients. These changes display a highly regional and
      disease subtype-dependent regulation that correlates with brain pathology. We
      demonstrate that selected miRNAs are enriched in sCJD isolated Argonaute(Ago)
      binding complexes in disease, indicating their incorporation into RNA-induced
      silencing complexes, and further suggesting their contribution to disease
      associated gene expression changes. Alterations in the miRNA-mRNA regulatory
      machinery and perturbed levels of miRNA biogenesis key components in sCJD brain
      samples reported here further implicate miRNAs in sCJD gene expression
      (de)regulation. We also show that a subset of sCJD-altered miRNAs are commonly
      changed in Alzheimer's disease, dementia with Lewy bodies and fatal familial
      insomnia, suggesting potential common mechanisms underlying these
      neurodegenerative processes. Additionally, we report no correlation between brain
      and cerebrospinal fluid (CSF) miRNA-profiles in sCJD, indicating that CSF-miRNA
      profiles do not faithfully mirror miRNA alterations detected in brain tissue of
      human prion diseases. Finally, utilizing a sCJD MM1 mouse model, we analyzed the
      miRNA deregulation patterns observed in sCJD in a temporal manner. While fourteen
      sCJD-related miRNAs were validated at clinical stages, only two of those were
      changed at early symptomatic phase, suggesting that the miRNAs altered in sCJD
      may contribute to later pathogenic processes. Altogether, the present work
      identifies alterations in the miRNA network, biogenesis and miRNA-mRNA silencing
      machinery in sCJD, whereby contributions to disease mechanisms deserve further
      investigation.

PMID- 29357387
TI  - The fungal myosin I is essential for Fusarium toxisome formation.
AB  - Myosin-I molecular motors are proposed to function as linkers between membranes
      and the actin cytoskeleton in several cellular processes, but their role in the
      biosynthesis of fungal secondary metabolites remain elusive. Here, we found that
      the myosin I of Fusarium graminearum (FgMyo1), the causal agent of Fusarium head
      blight, plays critical roles in mycotoxin biosynthesis. Inhibition of myosin I by
      the small molecule phenamacril leads to marked reduction in deoxynivalenol (DON)
      biosynthesis. FgMyo1 also governs translation of the DON biosynthetic enzyme Tri1
      by interacting with the ribosome-associated protein FgAsc1. Disruption of the
      ATPase activity of FgMyo1 either by the mutation E420K, down-regulation of FgMyo1
      expression or deletion of FgAsc1 results in reduced Tri1 translation. The DON
      biosynthetic enzymes Tri1 and Tri4 are mainly localized to subcellular structures
      known as toxisomes in response to mycotoxin induction and the FgMyo1-interacting
      protein, actin, participates in toxisome formation. The actin polymerization
      disruptor latrunculin A inhibits toxisome assembly. Consistent with this
      observation, deletion of the actin-associated proteins FgPrk1 and FgEnd3 also
      results in reduced toxisome formation. Unexpectedly, the FgMyo1-actin
      cytoskeleton is not involved in biosynthesis of another secondary metabolite
      tested. Taken together, this study uncovers a novel function of myosin I in
      regulating mycotoxin biosynthesis in filamentous fungi.

PMID- 29357388
TI  - Diagnosis of small pulmonary lesions by transbronchial lung biopsy with radial
      endobronchial ultrasound and virtual bronchoscopic navigation versus CT-guided
      transthoracic needle biopsy: A systematic review and meta-analysis.
AB  - BACKGROUND: Advances in bronchoscopy and CT-guided lung biopsy have improved the
      evaluation of small pulmonary lesions (PLs), leading to an increase in
      preoperative histological diagnosis. We aimed to evaluate the efficacy and safety
      of transbronchial lung biopsy using radial endobronchial ultrasound and virtual
      bronchoscopic navigation (TBLB-rEBUS&VBN) and CT-guided transthoracic needle
      biopsy (CT-TNB) for tissue diagnosis of small PLs. METHODS: A systematic search
      was performed in five electronic databases, including MEDLINE, EMBASE, Cochrane
      Library Central Register of Controlled Trials, Web of Science, and Scopus, for
      relevant studies in May 2016; the selected articles were assessed using meta
      analysis. The articles were limited to those published after 2000 that studied
      small PLs <= 3 cm in diameter. RESULTS: From 7345 records, 9 articles on the
      bronchoscopic (BR) approach and 15 articles on the percutaneous (PC) approach
      were selected. The pooled diagnostic yield was 75% (95% confidence interval [CI],
      69-80) using the BR approach and 93% (95% CI, 90-96) using the PC approach. For
      PLs <= 2 cm, the PC approach (pooled diagnostic yield: 92%, 95% CI: 88-95) was
      superior to the BR approach (66%, 95% CI: 55-76). However, for PLs > 2 cm but <=
      3 cm, the diagnostic yield using the BR approach was improved to 81% (95% CI, 75
      85). Complications of pneumothorax and hemorrhage were rare with the BR approach
      but common with the PC approach. CONCLUSIONS: CT-TNB was superior to TBLB
      rEBUS&VBN for the evaluation of small PLs. However, for lesions greater than 2
      cm, the BR approach may be considered considering its diagnostic yield of over
      80% and the low risk of procedure-related complications.

PMID- 29357392
TI  - Prevention, Detection, Evaluation, and Management of High Blood Pressure in
      Adults: Synopsis of the 2017 American College of Cardiology/American Heart
      Association Hypertension Guideline.
AB  - Description: In November 2017, the American College of Cardiology (ACC) and the
      American Heart Association (AHA) released a clinical practice guideline for the
      prevention, detection, evaluation, and treatment of high blood pressure (BP) in
      adults. This article summarizes the major recommendations. Methods: In 2014, the
      ACC and the AHA appointed a multidisciplinary committee to update previous
      reports of the Joint National Committee on Prevention, Detection, Evaluation, and
      Treatment of High Blood Pressure. The committee reviewed literature and
      commissioned systematic reviews and meta-analyses on out-of-office BP monitoring,
      the optimal target for BP lowering, the comparative benefits and harms of
      different classes of antihypertensive agents, and the comparative benefits and
      harms of initiating therapy with a single antihypertensive agent or a combination
      of 2 agents. Recommendations: This article summarizes key recommendations in the
      following areas: BP classification, BP measurement, screening for secondary
      hypertension, nonpharmacologic therapy, BP thresholds and cardiac risk estimation
      to guide drug treatment, treatment goals (general and for patients with diabetes
      mellitus, chronic kidney disease, and advanced age), choice of initial drug
      therapy, resistant hypertension, and strategies to improve hypertension control.

PMID- 29357389
TI  - Interferon regulatory factor 8 regulates caspase-1 expression to facilitate
      Epstein-Barr virus reactivation in response to B cell receptor stimulation and
      chemical induction.
AB  - Interferon regulatory factor 8 (IRF8), also known as interferon consensus
      sequence-binding protein (ICSBP), is a transcription factor of the IRF family.
      IRF8 plays a key role in normal B cell differentiation, a cellular process that
      is intrinsically associated with Epstein-Barr virus (EBV) reactivation. However,
      whether IRF8 regulates EBV lytic replication remains unknown. In this study, we
      utilized a CRISPR/Cas9 genomic editing approach to deplete IRF8 and found that
      IRF8 depletion dramatically inhibits the reactivation of EBV upon lytic
      induction. We demonstrated that IRF8 depletion suppresses the expression of a
      group of genes involved in apoptosis and thus inhibits apoptosis induction upon
      lytic induction by B cell receptor (BCR) stimulation or chemical induction. The
      protein levels of caspase-1, caspase-3 and caspase-8 all dramatically decreased
      in IRF8-depleted cells, which led to reduced caspase activation and the
      stabilization of KAP1, PAX5 and DNMT3A upon BCR stimulation. Interestingly,
      caspase inhibition blocked the degradation of KAP1, PAX5 and DNMT3A, suppressed
      EBV lytic gene expression and viral DNA replication upon lytic induction,
      suggesting that the reduced caspase expression in IRF8-depleted cells contributes
      to the suppression of EBV lytic replication. We further demonstrated that IRF8
      directly regulates CASP1 (caspase-1) gene expression through targeting its gene
      promoter and knockdown of caspase-1 abrogates EBV reactivation upon lytic
      induction, partially through the stabilization of KAP1. Together our study
      suggested that, by modulating the activation of caspases and the subsequent
      cleavage of KAP1 upon lytic induction, IRF8 plays a critical role in EBV lytic
      reactivation.

PMID- 29357391
TI  - Iron deficiency across chronic kidney disease stages: Is there a reverse gender
      pattern?
AB  - In non-dialysis chronic kidney disease patients, looking for iron deficiency is
      highly variable in practice and there is a great variability regarding the
      cutoffs used to treat iron deficiency. The aim of this study is to investigate
      the degree of iron deficiency in non-dialysis chronic kidney disease patients on
      erythropoiesis-stimulating agents. We included all non-dialysis chronic kidney
      disease patients that applied to the Lebanese Ministry of Public Health for
      erythropoiesis-stimulating agents' coverage during a 5-month period. Iron
      requirement was assessed based on two guidelines' target-to-treat cutoffs: 1
      ferritin <100 ng/ml and/or TSAT < 20% (KDOQI 2006), 2- ferritin <=500 ng/ml and
      TSAT <=30% (KDIGO 2012). A total of 238 CKD patients were included over 5 months.
      All patients had a ferritin level in their record and 64% had an available TSAT.
      Median age was 71.0 (59.8-79.3) years and 61.8% were female. All had an eGFR<60
      ml/min. The proportion of patients found to require iron therapy ranged between
      48 and 78% with a trend towards higher values when using KDIGO-based criteria.
      Using ANCOVA test, inverse normal transformations of ferritin and TSAT showed a
      reverse pattern between men and women with women being more iron deficient in the
      early stage. Iron deficiency is highly prevalent in non-dialysis chronic kidney
      disease patients on erythropoiesis-stimulating agents' therapy. These findings
      reflect a lack in effective iron supplementation when managing anemia in pre
      dialysis patients, especially in men at advanced stages. Renal societies should
      spread awareness about iron deficiency screening in those patients.

PMID- 29357390
TI  - Herpesvirus deconjugases inhibit the IFN response by promoting TRIM25
      autoubiquitination and functional inactivation of the RIG-I signalosome.
AB  - The N-terminal domains of the herpesvirus large tegument proteins encode a
      conserved cysteine protease with ubiquitin- and NEDD8-specific deconjugase
      activity. The proteins are expressed during the productive virus cycle and are
      incorporated into infectious virus particles, being delivered to the target cells
      upon primary infection. Members of this viral enzyme family were shown to
      regulate different aspects of the virus life cycle and the innate anti-viral
      response. However, only few substrates have been identified and the mechanisms of
      these effects remain largely unknown. In order to gain insights on the substrates
      and signaling pathways targeted by the viral enzymes, we have used co
      immunoprecipitation and mass spectrometry to identify cellular proteins that
      interact with the Epstein-Barr virus encoded homologue BPLF1. Several members of
      the 14-3-3-family of scaffold proteins were found amongst the top hits of the
      BPLF1 interactome, suggesting that, through this interaction, BPLF1 may regulate
      a variety of cellular signaling pathways. Analysis of the shared protein
      interaction network revealed that BPLF1 promotes the assembly of a tri-molecular
      complex including, in addition to 14-3-3, the ubiquitin ligase TRIM25 that
      participates in the innate immune response via ubiquitination of cytosolic
      pattern recognition receptor, RIG-I. The involvement of BPLF1 in the regulation
      of this signaling pathway was confirmed by inhibition of the type-I IFN responses
      in cells transfected with a catalytically active BPLF1 N-terminal domain or
      expressing the endogenous protein upon reactivation of the productive virus
      cycle. We found that the active viral enzyme promotes the dimerization and
      autoubiquitination of TRIM25. Upon triggering of the IFN response, RIG-I is
      recruited to the complex but ubiquitination is severely impaired, which
      functionally inactivates the RIG-I signalosome. The capacity to bind to and
      functionally inactivate the RIG-I signalosome is shared by the homologues encoded
      by other human herpesviruses.

PMID- 29357393
TI  - Effects of Bilateral Hearing Aid Use on Balance in Experienced Adult Hearing Aid
      Users.
AB  - Purpose: The purpose of this study was to evaluate the balance of experienced
      adult hearing aid users with and without their hearing aids via computerized
      posturography. Method: Computerized posturography was accomplished by employing
      the Sensory Organization Test (SOT) on the NeuroCom Balance Master (Natus Medical
      Incorporated). The SOT assessed each participant's balance and the strategy used
      to maintain balance in 6 progressively challenging conditions. Twenty-two adults
      using bilateral at-the-ear hearing aids participated in the study. All
      participants completed all SOT protocols with and without their hearing aids.
      Results: No statistically significant differences in participants' balance were
      identified regardless of the presence or absence of their hearing aids during the
      SOT. Conclusions: These results failed to support previous research, which
      indicated that amplification of auditory input could benefit balance in
      individuals with hearing and balance disorders. Further research utilizing
      randomized controlled trials is needed to resolve the disparity between the
      current results and those of previous studies.

PMID- 29357395
TI  - Expansion of the Classification System for Eagle Syndrome.

PMID- 29357394
TI  - Associations Between Marijuana Use and Cardiovascular Risk Factors and Outcomes:
      A Systematic Review.
AB  - Background: Marijuana use is increasing in the United States, and its effect on
      cardiovascular health is unknown. Purpose: To review harms and benefits of
      marijuana use in relation to cardiovascular risk factors and clinical outcomes.
      Data Sources: PubMed, MEDLINE, EMBASE, PsycINFO, and the Cochrane Library between
      1 January 1975 and 30 September 2017. Study Selection: Observational studies that
      were published in English, enrolled adults using any form of marijuana, and
      reported on vascular risk factors (hyperglycemia, diabetes, dyslipidemia, and
      obesity) or on outcomes (stroke, myocardial infarction, cardiovascular mortality,
      and all-cause mortality in cardiovascular cohorts). Data Extraction: Study
      characteristics and quality were assessed by 4 reviewers independently; strength
      of evidence for each outcome was graded by consensus. Data Synthesis: 13 and 11
      studies examined associations between marijuana use and cardiovascular risk
      factors and clinical outcomes, respectively. Although 6 studies suggested a
      metabolic benefit from marijuana use, they were based on cross-sectional designs
      and were not supported by prospective studies. Evidence examining the effect of
      marijuana on diabetes, dyslipidemia, acute myocardial infarction, stroke, or
      cardiovascular and all-cause mortality was insufficient. Although the current
      literature includes several long-term prospective studies, they are limited by
      recall bias, inadequate exposure assessment, minimal marijuana exposure, and a
      predominance of low-risk cohorts. Limitation: Poor- or moderate-quality data,
      inadequate assessment of marijuana exposure and minimal exposure in the
      populations studied, and variation in study design. Conclusion: Evidence
      examining the effect of marijuana on cardiovascular risk factors and outcomes,
      including stroke and myocardial infarction, is insufficient. Primary Funding
      Source: National Heart, Lung, and Blood Institute. (PROSPERO: CRD42016051297).

PMID- 29357396
TI  - The 2017 American College of Cardiology/American Heart Association Hypertension
      Guideline: A Resource for Practicing Clinicians.

PMID- 29357397
TI  - Hypertension Limbo: Balancing Benefits, Harms, and Patient Preferences Before We
      Lower the Bar on Blood Pressure.

PMID- 29357398
TI  - Antithyroid Drugs and Congenital Malformations: A Nationwide Korean Cohort Study.
AB  - Background: Untreated or insufficiently treated Graves disease in pregnancy may
      pose risks to both mother and fetus. Antithyroid drugs (ATDs) are the treatment
      mainstay, but the potential teratogenic effect of these drugs has prompted
      clinicians to question the safe management of this vulnerable population.
      Objective: To examine the association between maternal prescriptions for ATDs and
      congenital malformations in live births. Design: Nationwide cohort study.
      Setting: Korean National Health Insurance database. Participants: A cohort of 2
      886 970 completed pregnancies linked to live-born infants in 2 210 253 women
      between 2008 and 2014. Intervention: Maternal prescriptions for ATDs in the first
      trimester. Measurements: The risk for overall and organ-specific congenital
      malformations in offspring, with logistic regression models used to control for
      potential confounders. Results: 12 891 pregnancies (0.45%) were exposed to ATDs
      during the first trimester. The prevalence of malformations in exposed offspring
      was 7.27%, compared with 5.94% in offspring of women who were not prescribed ATDs
      during pregnancy (P < 0.001) (adjusted odds ratio, 1.19 [95% CI, 1.12 to 1.28]).
      Absolute increases in the prevalence of congenital malformations per 1000 live
      births were 8.81 cases (CI, 3.92 to 13.70 cases) for propylthiouracil alone,
      17.05 cases (CI, 1.94 to 32.15 cases) for methimazole (MMI) alone, and 16.53
      cases (CI, 4.73 to 28.32 cases) for propylthiouracil and MMI, compared with
      pregnancies without ATD prescriptions. In the MMI group, a high cumulative dose
      (>495 mg) during the first trimester was associated with an increased risk for
      malformations compared with a low dose (1 to 126 mg) (adjusted odds ratio, 1.87
      [CI, 1.06 to 3.30]). Limitation: The study used a prescription claims database to
      assess ATD exposure. Conclusion: Exposure to ATDs during the first trimester was
      associated with increased risk for congenital malformations, particularly for
      pregnancies in which women received prescriptions for MMI or both ATDs. Primary
      Funding Source: None.

PMID- 29357401
TI  - Organizing a Proficiency Testing Program on Stamp Impressions Examination in
      Accordance with ISO/IEC 17043 Requirements.
AB  - Stamps and stamp impressions examinations are based on matching defects and
      design details on the questioned and control samples. These examinations are
      routinely carried out by document examiners around the world. International
      proficiency tests for questioned documents examination have been available for
      decades while similar programs specifically focusing on stamp impressions
      examination are rare. This study reported a recent proficiency testing program on
      stamp impressions examination organized by an accredited provider in accordance
      with ISO/IEC 17043 requirements. Twenty-four forensic laboratories registered for
      the program. Apart from giving details on the design and operation of the
      program, this study also aimed to provide the limitations and difficulties
      encountered in sample preparations, homogeneity, and stability tests of the
      testing materials. Various comments and feedbacks received from the participants,
      particularly in respect of examination approaches, challenges faced by the
      participants in forming conclusions and their suggestions for further improvement
      would be evaluated.

PMID- 29357400
TI  - Bioinformatics Approach to Assess the Biogeographical Patterns of Soil
      Communities: The Utility for Soil Provenance.
AB  - Soil DNA profiling has potential as a forensic tool to establish a link between
      soil collected at a crime scene and soil recovered from a suspect. However, a
      quantitative measure is needed to investigate the spatial/temporal variability
      across multiple scales prior to their application in forensic science. In this
      study, soil DNA profiles across Miami-Dade, FL, were generated using length
      heterogeneity PCR to target four taxa. The objectives of this study were to (i)
      assess the biogeographical patterns of soils to determine whether soil biota is
      spatially correlated with geographic location and (ii) evaluate five machine
      learning algorithms for their predictive ability to recognize biotic patterns
      which could accurately classify soils at different spatial scales regardless of
      seasonal collection. Results demonstrate that soil communities have unique
      patterns and are spatially autocorrelated. Bioinformatic algorithms could
      accurately classify soils across all scales with Random Forest significantly
      outperforming all other algorithms regardless of spatial level.

PMID- 29357402
TI  - Sudden Death from Cardiopulmonary Arrest on Arrival of a Patient with Pulmonary
      Tuberculosis: A Case Diagnosed by Postmortem CT and Autopsy.
AB  - Sudden death due to massive hemoptysis during management of tuberculosis occurs
      in a considerable number of patients. However, when massive airway hemorrhage
      occurs in a patient in whom tuberculosis has not been confirmed and a blood is
      not apparent externally on the face/body, it is difficult to immediately identify
      the cause of death as airway obstruction by tuberculous bleeding in the airway.
      We encountered an 83-year-old Japanese woman with her medical history included
      treatment of tuberculosis in her 20s who was in cardiopulmonary arrest on arrival
      (CPAOA), and the cause of sudden death could not initially be identified.
      Postmortem CT (PMCT) and autopsy revealed that the cause of sudden death was
      airway obstruction/asphyxia by tuberculous massive airway hemorrhage.
      Identification of the cause of death facilitated a subsequent active contact
      investigation and led to prevention of secondary tuberculosis infection.

PMID- 29357403
TI  - Accurate determination of a novel vasodilatory beta-blocker TJ0711 using LC
      MS/MS: Resolution of an isobaric metabolite interference in dog plasma.
AB  - A rapid, robust and sensitive liquid chromatography-tandem mass spectrometry
      method was developed and validated for bioanalysis of TJ0711, a novel
      vasodilatory beta-blocker in dog plasma. This assay is able to
      chromatographically separate TJ0711 from its isobaric metabolite as well as
      glucuronide conjugates. Chromatographic separation was achieved on a Welch
      Ultimate-XB C18 column (2.1 * 100 mm, 3 MUm). The analyte and internal standard
      (propranolol) were extracted from plasma by liquid-liquid extraction using ethyl
      acetate. The mass spectrometric detection was carried out in positive ion
      multiple reaction monitoring mode. Good linearity was obtained over the
      concentration range of 0.5-500 ng/mL (r > 0.99) for TJ0711. Moreover, the method
      had good accuracy (RE ranging from -2.70 to -0.32%) and precision (RSD < 7.55%).
      TJ0711 was stable in dog plasma for at least 6 h at ambient temperature, for at
      least 30 days at -20 degrees C and after three freeze-thaw cycles. This method
      was successfully applied to a preclinical pharmacokinetic study and the results
      demonstrated linear pharmacokinetics of TJ0711 over a dose range from 0.03 to 0.3
      mg/kg. No significant gender differences were observed in TJ0711 plasma
      pharmacokinetic parameters.

PMID- 29357404
TI  - Robot-assisted partial nephrectomy for large renal masses: a multi-institutional
      series.
AB  - OBJECTIVES: To compare peri-operative outcomes after robot-assisted partial
      nephrectomy (RAPN) for cT2a (7 to <10 cm) to cT1 tumours. MATERIALS AND METHODS:
      Patients with a cT1a (n = 1 358, 76.4%), cT1b (n = 379, 21.3%) or cT2a (n = 41,
      2.3%) renal mass were identified from a multi-institutional RAPN database. Intra-
      and postoperative outcomes were compared for cT2a masses vs cT1a and cT1b masses
      using multivariable regression models (linear, logistic, Poisson etc.), adjusting
      for operating surgeon and a modified R.E.N.A.L. nephrometry score that excluded
      the radius component. RESULTS: The median sizes for cT1a, cT1b and cT2a tumours
      were 2.5, 5.0 and 8.0 cm, respectively (P < 0.001) with modified R.E.N.A.L.
      nephrometry scores being 6.0, 6.5 and 7.0, respectively (cT1a, P < 0.001; cT1b, P
      = 0.105). RAPN for cT2a vs cT1a masses was associated with a 12% increase in
      operating time (P < 0.001), a 32% increase in estimated blood loss (P < 0.001), a
      7% increase in ischaemia time (P = 0.008), a 3.93 higher odds of acute kidney
      injury at discharge (95% confidence interval [CI] 1.33, 8.76; P = 0.009) and a
      higher risk of recurrence (hazard ratio [HR] 10.9, 95% CI 1.31, 92.2; P = 0.027).
      RAPN for cT2a vs cT1b masses was associated with a 12% increase in blood loss (P
      = 0.036), a 5% increase in operating time (P = 0.062) and a marginally higher
      risk of recurrence (HR 11.2, 95% CI 0.77, 11.5; P = 0.059). RAPN for cT2a tumours
      was not associated with differences in complications (cT1a, P = 0.535; cT1b, P =
      0.382), positive margins (cT1a, P = 0.972; cT1b, P = 0.681), length of stay
      (cT1a, P = 0.507; cT1b, P = 0.513) or renal function decline up to 24 months post
      RAPN (cT1a, P = 0.124; cT1b, P = 0.467). CONCLUSION: For T2a tumours RAPN is a
      feasible treatment option in a select patient population when performed by
      experienced surgeons in institutions equipped to manage postoperative
      complications. Although RAPN was associated with greater blood loss and longer
      operating and ischaemia time in T2a tumours, it was not associated with greater
      complication or positive surgical margin rates compared with T1 tumours. Renal
      function preservation rates were equivalent for up to 24 months postoperatively;
      however, 12-month recurrence-free survival was significantly lower in the T2a
      group. Extended follow-up is required to further evaluate long-term survival.

PMID- 29357405
TI  - Combat biofilm by bacteriostatic aptamer-functionalized graphene oxide.
AB  - Biofilms are the main reason for a large number deaths and high health costs.
      Their better protection compared to planktonic form against conventional
      antibiotics leads to poor treatment efficiency. Nanoagent-targeted delivery is a
      promising avenue for disease therapeutic, but its application targeting biofilms
      has not been reported currently. The roles, if any, of aptamers acting as
      delivery carrier and targeting factor, the graphene oxide (GO), and GO modified
      with aptamers against biofilms were then systematically evaluated. Here, we
      successfully developed an aptamer-targeted GO strategy against biofilms. We
      investigated the efficacy of aptamer-GO conjugates by UV spectrophotometer,
      inverted microscopy, and atomic force microscopy; 93.5 +/- 3.4% Salmonella
      typhimurium biofilms were inhibited and 84.6 +/- 5.1% of biofilms were dispersed
      by a ST-3-GO conjugate. More importantly, this conjugate represented
      distinctively toxicity to S. typhimurium. Thus, this strategy significantly
      displays excellent antibiofilm properties and may serve as a long-term solution
      for biofilm control.

PMID- 29357406
TI  - Extremely low-frequency electromagnetic fields accelerates wound healing
      modulating MMP-9 and inflammatory cytokines.
AB  - OBJECTIVES: In our previous reports, we have demonstrated that extremely low
      frequency electromagnetic fields (ELF-EMF) exposure enhances the proliferation of
      keratinocyte. The present study aimed to clarify effects of ELF-EMF on wound
      healing and molecular mechanisms involved, using a scratch in vitro model.
      MATERIALS AND METHODS: The wounded monolayer cultures of human immortalized
      keratinocytes (HaCaT), at different ELF-EMF and Sham exposure times were
      monitored under an inverted microscope. The production and expression of IL
      1beta, TNF-alpha, IL-18 and IL-18BP were measured by enzyme-linked immunosorbent
      assay and quantitative real-time PCR. The activity and the expression of matrix
      metalloproteinases (MMP)-2/9 was evaluated by zymography and Western blot
      analysis, respectively. Signal transduction proteins expression (Akt and ERK) was
      measured by Western blot. RESULTS: The results of wound healing in vitro assay
      revealed a significant reduction of cell-free area time-dependent in ELF-EMF
      exposed cells compared to Sham condition. Gene expression and release of
      cytokines analysed were significantly increased in ELF-EMF-exposed cells. Our
      results further showed that ELF-EMF exposure induced the activity and expressions
      of MMP-9. Molecular data showed that effects of ELF-EMF might be mediated via Akt
      and ERK signal pathway, as demonstrated using their specific inhibitors.
      CONCLUSIONS: Our results highlight ability of ELF-EMF to modulate inflammation
      mediators and keratinocyte proliferation/migration, playing an important role in
      wound repair. The ELF-EMF accelerates wound healing modulating expression of the
      MMP-9 via Akt/ERK pathway.

PMID- 29357408
TI  - Holding tight and staying true: generation of a new tamoxifen-inducible,
      principal cell-specific mouse.

PMID- 29357407
TI  - Informal caregivers' experiences of caring for people receiving dialysis: A mixed
      methods systematic review.
AB  - BACKGROUND: Living with end stage kidney disease and having dialysis is
      burdensome, and there is a need for support from informal caregivers (i.e. family
      members and friends). Renal health professionals readily acknowledge and value
      the support provided by caregivers although the activities and experiences of
      caring for a loved-one who is receiving dialysis is less well understood.
      OBJECTIVES: To review studies about the perspectives and experiences of family
      members and friends who provide support for adults receiving either haemodialysis
      or peritoneal dialysis. METHODS: A mixed-methods systematic review was conducted.
      Eight databases (Medline, CINAHL, EMBASE, PsycINFO, Proquest, Web of Science,
      Cochrane Library and JBI library) were comprehensively searched using relevant
      key words for studies regardless of design published in English from January 2006
      to July 2017. RESULTS: Twenty studies were included in this review. Informal
      caregivers undertake many everyday activities as well as a range of dialysis
      specific activities, report an elevated level of burden, feel overwhelmed,
      experience social isolation, and also need to consider their own health. A unique
      finding was that caregivers also experienced personal growth that may defuse the
      impact of caregiving burden and to help them develop a sense of resilience to
      sustain the support through the tough times and for many years. CONCLUSION: This
      review substantiates that caregiver burden is due to the unrelenting nature of
      complex dialysis-specific activities although resilience often develops.
      Additional research is necessary to understand social support in this context and
      how health teams can assist caregivers further.

PMID- 29357409
TI  - N-acetyl-cysteine increases cellular dysfunction in progressive chronic kidney
      damage after acute kidney injury by dampening endogenous antioxidant responses.
AB  - Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury
      (AKI), but their role in any associated progress to chronic kidney disease (CKD)
      remains unclear. Antioxidant therapies often benefit AKI, but their benefits in
      CKD are controversial since clinical and preclinical investigations often
      conflict. Here we examined the influence of the antioxidant N-acetyl-cysteine
      (NAC) on oxidative stress and mitochondrial function during AKI (20-min bilateral
      renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies
      in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post
      IR (21d-IR). NAC treatment resulted in the following: prevented proximal tubular
      epithelial cell apoptosis at early IR (40-min postischemia), yet enhanced
      interstitial cell proliferation at 21d-IR; increased transforming growth factor
      beta1 expression independent of IR time; and significantly dampened nuclear
      factor-like 2-initiated cytoprotective signaling at early IR. In the long term,
      NAC enhanced cellular metabolic impairment demonstrated by increased peroxisome
      proliferator activator-gamma serine-112 phosphorylation at 21d-IR. Intravital
      multiphoton microscopy revealed increased endogenous fluorescence of nicotinamide
      adenine dinucleotide (NADH) in cortical tubular epithelial cells during ischemia,
      and at 21d-IR that was not attenuated with NAC. Fluorescence lifetime imaging
      microscopy demonstrated persistent metabolic impairment by increased free/bound
      NADH in the cortex at 21d-IR that was enhanced by NAC. Increased mitochondrial
      dysfunction in remnant tubular cells was demonstrated at 21d-IR by
      tetramethylrhodamine methyl ester fluorimetry. In summary, NAC enhanced
      progression to CKD following AKI not only by dampening endogenous cellular
      antioxidant responses at time of injury but also by enhancing persistent kidney
      mitochondrial and metabolic dysfunction.

PMID- 29357410
TI  - Tamm-Horsfall protein/uromodulin deficiency elicits tubular compensatory
      responses leading to hypertension and hyperuricemia.
AB  - Expression of Tamm-Horsfall protein (THP or uromodulin) is highly restricted to
      the kidney thick ascending limb (TAL) of loop of Henle. Despite the unique
      location and recent association of THP gene mutations with hereditary uromodulin
      associated kidney disease and THP single nucleotide polymorphisms with chronic
      kidney disease and hypertension, the physiological function(s) of THP and its
      pathological involvement remain incompletely understood. By studying age
      dependent changes of THP knockout (KO) mice, we show here that young KO mice had
      significant salt and water wasting but were partially responsive to furosemide,
      due to decreased luminal translocation of Na-K-Cl cotransporter 2 (NKCC2) in the
      TAL. Aged THP KO mice were, however, markedly oliguric and unresponsive to
      furosemide, and their NKCC2 was localized primarily in the cytoplasm as evidenced
      by lipid raft floatation assay, cell fractionation, and confocal and
      immunoelectron microscopy. These aged KO mice responded to metolazone and
      acetazolamide, known to target distal and proximal tubules, respectively. They
      also had marked upregulation of renin in juxtaglomerular apparatus and serum, and
      they were hypertensive. Finally, the aged THP KO mice had significant
      upregulation of Na-coupled urate transporters Slc5a8 and Slc22a12 as well as
      sodium-hydrogen exchanger 3 (NHE3) in the proximal tubule and elevated serum uric
      acid and allantoin. Collectively, our results suggest that THP deficiency can
      cause progressive disturbances in renal functions via initially NKCC2 dysfunction
      and later compensatory responses, resulting in prolonged activation of the renin
      angiotensin-aldosterone axis and hyperuricemia.

PMID- 29357412
TI  - beta-Catenin in stromal progenitors controls medullary stromal development.
AB  - The renal stroma is a population of matrix-producing fibroblast cells that serves
      as a structural framework for the kidney parenchyma. The stroma also regulates
      branching morphogenesis and nephrogenesis. In the mature kidney, the stroma forms
      at least three distinct cell populations: the capsular, cortical, and medullary
      stroma. These distinct stromal populations have important functions in kidney
      development, maintenance of kidney function, and disease progression. However,
      the development, differentiation, and maintenance of the distinct stroma
      populations are not well defined. Using a mouse model with beta-catenin
      deficiency in the stroma cell population, we demonstrate that beta-catenin is not
      involved in the formation of the stromal progenitors nor in the formation of the
      cortical stroma population. In contrast, beta-catenin does control the
      differentiation of stromal progenitors to form the medullary stroma. In the
      absence of stromal beta-catenin, there is a marked reduction of medullary stromal
      markers. As kidney development continues, the maldifferentiated stromal cells
      locate deeper within the kidney tissue and are eliminated by the activation of an
      intrinsic apoptotic program. This leads to significant reductions in the
      medullary stroma population and the lack of medulla formation. Taken together,
      our results indicate that stromal beta-catenin is essential for kidney
      development by regulating medulla formation through the differentiation of
      medullary stromal cells.

PMID- 29357411
TI  - ApoL1 renal risk variants induce aberrant THP-1 monocyte differentiation and
      increase eicosanoid production via enhanced expression of cyclooxygenase-2.
AB  - Apolipoprotein L1 ( ApoL1) genetic variants are strongly associated with kidney
      diseases. We investigated the role of ApoL1 variants in monocyte differentiation
      and eicosanoid production in macrophages, as activated tissue macrophages in
      kidney might contribute to kidney injury. In human monocyte THP-1 cells,
      transient overexpression of ApoL1 (G0, G1, G2) by transfection resulted in a 5-
      to 11-fold increase in CD14 and CD68 gene expression, similar to that seen with
      phorbol-12-myristate acetate treatment. All ApoL1 variants caused monocytes to
      differentiate into atypical M1 macrophages with marked increase in M1 markers
      CD80, TNF, IL1B, and IL6 and modest increase in the M2 marker CD163 compared with
      control cells. ApoL1-G1 transfection induced additional CD206 and TGFB1
      expression, and ApoL1-G2 transfection induced additional CD204 and TGFB1
      expression. Gene expression of prostaglandin E2 (PGE2) synthase and thromboxane
      synthase and both gene and protein expression of cyclooxygenase-2 (COX-2) were
      increased by ApoL1-G1 and -G2 variants compared with -G0 transfection. Higher
      levels of PGE2 and thromboxane B2, a stable metabolite of thromboxane A2, and
      transforming growth factor (TGF)-beta1 were released into the supernatant of
      cultured THP-1 cells transfected with ApoL1-G1 and -G2, but not -G0. The increase
      in PGE2, thromboxane B2, and TGF-beta1 was inhibited by COX-2-specific inhibitor
      CAY10404 but not by COX-1-specific inhibitor SC-560. These results demonstrate a
      novel role of ApoL1 variants in the regulation of monocyte differentiation and
      eicosanoid metabolism, which could modify the immune response and promote
      inflammatory signaling within the local targeted organs and tissues including the
      kidney.

PMID- 29357413
TI  - Defective interplay between mTORC1 activity and endoplasmic reticulum stress
      unfolded protein response in uremic vascular calcification.
AB  - Vascular calcification increases the risk of cardiovascular disease and death in
      patients with chronic kidney disease (CKD). Increased activity of mammalian
      target of rapamycin complex 1 (mTORC1) and endoplasmic reticulum (ER) stress
      unfolded protein response (UPR) are independently reported to partake in the
      pathogenesis of vascular calcification in CKD. However, the association between
      mTORC1 activity and ER stress-UPR remains unknown. We report here that components
      of the uremic state [activation of the receptor for advanced glycation end
      products (RAGE) and hyperphosphatemia] potentiate vascular smooth muscle cell
      (VSMC) calcification by inducing persistent and exaggerated activity of mTORC1.
      This gives rise to prolonged and excessive ER stress-UPR as well as attenuated
      levels of sestrin 1 ( Sesn1) and Sesn3 feeding back to inhibit mTORC1 activity.
      Activating transcription factor 4 arising from the UPR mediates cell death via
      expression of CCAAT/enhancer-binding protein (c/EBP) homologous protein (CHOP),
      impairs the generation of pyrophosphate, a potent inhibitor of mineralization,
      and potentiates VSMC transdifferentiation to the osteochondrocytic phenotype.
      Short-term treatment of CKD mice with rapamycin, an inhibitor of mTORC1, or
      tauroursodeoxycholic acid, a bile acid that restores ER homeostasis, normalized
      mTORC1 activity, molecular markers of UPR, and calcium content of aortas.
      Collectively, these data highlight that increased and/or protracted mTORC1
      activity arising from the uremic state leads to dysregulated ER stress-UPR and
      VSMC calcification. Manipulation of the mTORC1-ER stress-UPR pathway opens up new
      therapeutic strategies for the prevention and treatment of vascular calcification
      in CKD.

PMID- 29357414
TI  - Effects of a high-sodium/low-potassium diet on renal calcium, magnesium, and
      phosphate handling.
AB  - The distal convoluted tubule (DCT) of the kidney plays an important role in blood
      pressure regulation by modulating Na+ reabsorption via the Na+-Cl- cotransporter
      (NCC). A diet containing high salt (NaCl) and low K+ activates NCC, thereby
      causing Na+ retention and a rise in blood pressure. Since high blood pressure,
      hypertension, is associated with changes in serum calcium (Ca2+) and magnesium
      (Mg2+) levels, we hypothesized that dietary Na+ and K+ intake affects Ca2+ and
      Mg2+ transport in the DCT. Therefore, the present study aimed to investigate the
      effect of a high-Na+/low-K+ diet on renal Ca2+ and Mg2+ handling. Mice were
      divided in four groups and fed a normal-Na+/normal-K+, normal-Na+/low-K+, high
      Na+/normal-K+, or high-Na+/low-K+ diet for 4 days. Serum and urine were collected
      for electrolyte and hormone analysis. Gene and protein expression of electrolyte
      transporters were assessed in kidney and intestine by qPCR and immunoblotting.
      Whereas Mg2+ homeostasis was not affected, the mice had elevated urinary Ca2+ and
      phosphate (Pi) excretion upon high Na+ intake, as well as significantly lower
      serum Ca2+ levels in the high-Na+/low-K+ group. Alterations in the gene and
      protein expression of players involved in Ca2+ and Pi transport indicate that
      reabsorption in the proximal tubular and TAL is affected, while inducing a
      compensatory response in the DCT. These effects may contribute to the negative
      health impact of a high-salt diet, including kidney stone formation, chronic
      kidney disease, and loss of bone mineral density.

PMID- 29357415
TI  - Interfering RNA against PKC-alpha inhibits TNF-alpha-induced IP3R1 expression and
      improves glomerular filtration rate in rats with fulminant hepatic failure.
AB  - We have reported that tumor necrosis factor-alpha (TNF-alpha) is critical for
      reduction of glomerular filtration rate (GFR) in rats with fulminant hepatic
      failure (FHF). The present study aims to evaluate the underlying mechanisms of
      decreased GFR during acute hepatic failure. Rats with FHF induced by d
      galactosamine plus lipopolysaccharide (GalN/LPS) were injected intravenously with
      recombinant lentivirus harboring short hairpin RNA against the protein kinase C
      alpha ( PKC-alpha) gene (Lenti-shRNA-PKC-alpha). GFR, serum levels of
      aminotransferases, creatinine, urea nitrogen, potassium, sodium, chloride, TNF
      alpha, and endothelin-1 (ET-1), as well as type 1 inositol 1,4,5-trisphosphate
      receptor (IP3R1) expression in renal tissue were assessed. The effects of PKC
      alpha silencing on TNF-alpha-induced IP3R1, specificity protein 1 (SP-1), and c
      Jun NH2-terminal kinase (JNK) expression, as well as cytosolic calcium content
      were determined in glomerular mesangial cell (GMCs) with RNAi against PKC-alpha.
      Renal IP3R1 overexpression was abrogated by pre-treatment with Lenti-shRNA-PKC
      alpha. The PKC-alpha silence significantly improved the compromised GFR, reduced
      Cr levels, and reversed the decrease in glomerular inulin space and the increase
      in glomerular calcium content in GalN/LPS-exposed rats. TNF-alpha treatment
      increased expression of PKC-alpha, IP3R1, specificity protein 1 (SP-1), JNK, and
      p-JNK in GMCs and increased Ca2 + release and binding activity of SP-1 to the
      IP3R1 promoter. These effects were blocked by transfection of siRNA against the
      PKC-alpha gene, and the PKC-alpha gene silence also restored cytosolic Ca2+
      concentration. RNAi targeting PKC-alpha inhibited TNF-alpha-induced IP3R1
      overexpression and in turn improved compromised GFR in the development of acute
      kidney injury during FHF in rats.

PMID- 29357416
TI  - Improved protocols for the study of urinary electrolyte excretion and blood
      pressure in rodents: use of gel food and stepwise changes in diet composition.
AB  - Many experimental protocols in rodents require the comparison of groups that are
      fed different diets. Changes in dietary electrolyte and/or fat content can
      influence food intake, which can potentially introduce bias or confound the
      results. Unpalatable diets slow growth or cause weight loss, which is exacerbated
      by housing the animals in individual metabolic cages or by surgery. For balance
      studies in mice, small changes in body weight and food intake and low urinary
      flow can amplify these challenges. Powder food can be administered as gel with
      the addition of a desired amount of water, electrolytes, drugs (if any), and a
      small amount of agar. We describe here how the use of gel food to vary water, Na,
      K, and fat content can reduce weight loss and improve reproducibility of intake,
      urinary excretion, and blood pressure in rodents. In addition, mild food
      restriction reduces the interindividual variability and intergroup differences in
      food intake and associated variables, thus improving the statistical power of an
      experiment. Finally, we also demonstrate the advantages of using gel food for
      weight-based drug dosing. These protocols can improve the accuracy and
      reproducibility of experimental data where dietary manipulations are needed and
      are especially advisable in rodent studies related to water balance, obesity, and
      blood pressure.

PMID- 29357417
TI  - Array profiling reveals contribution of Cthrc1 to growth of the denervated rat
      urinary bladder.
AB  - Bladder denervation and bladder outlet obstruction are urological conditions that
      cause bladder growth. Transcriptomic surveys in outlet obstruction have
      identified differentially expressed genes, but similar studies following
      denervation have not been done. This was addressed using a rat model in which the
      pelvic ganglia were cryo-ablated followed by bladder microarray analyses. At 10
      days following denervation, bladder weight had increased 5.6-fold, and 2,890
      mRNAs and 135 micro-RNAs (miRNAs) were differentially expressed. Comparison with
      array data from obstructed bladders demonstrated overlap between the conditions,
      and 10% of mRNAs changed significantly and in the same direction. Many mRNAs,
      including collagen triple helix repeat containing 1 ( Cthrc1), Prc1, Plod2, and
      Dkk3, and miRNAs, such as miR-212 and miR-29, resided in the shared signature.
      Discordantly regulated transcripts in the two models were rare, making up for
      <0.07% of all changes, and the gene products in this category localized to the
      urothelium of normal bladders. These transcripts may potentially be used to
      diagnose sensory denervation. Western blotting demonstrated directionally
      consistent changes at the protein level, with increases of, e.g., Cthrc1, Prc1,
      Plod2, and Dkk3. We chose Cthrc1 for further studies and found that Cthrc1 was
      induced in the smooth muscle cell (SMC) layer following denervation. TGF-beta1
      stimulation and miR-30d-5p inhibition increased Cthrc1 in bladder SMCs, and
      knockdown and overexpression of Cthrc1 reduced and increased SMC proliferation.
      This work defines common and distinguishing features of bladder denervation and
      obstruction and suggests a role for Cthrc1 in bladder growth following
      denervation.

PMID- 29357418
TI  - Endogenous H2S sensitizes PAR4-induced bladder pain.
AB  - Bladder pain is a prominent symptom of interstitial cystitis/painful bladder
      syndrome. Hydrogen sulfide (H2S) generated by cystathionine beta-synthase (CBS)
      or cystathionine gamma-lyase (CSE) facilitates bladder hypersensitivity. We
      assessed involvement of the H2S pathway in protease-activated receptor 4 (PAR4)
      induced bladder pain. A bladder pain model was induced by intravesical
      instillation of PAR4-activating peptide in mice. The role of H2S in this model
      was evaluated by intraperitoneal preadministration of d,l-propargylglycine (PAG),
      aminooxyacetic acid (AOAA), or S-adenosylmethionine or the preintravesical
      administration of NaHS. SV-HUC-1 cells were treated in similar manners.
      Assessments of CBS, CSE, and macrophage migration inhibitory factor (MIF)
      expression, bladder voiding function, bladder inflammation, H2S production, and
      referred bladder pain were performed. The CSE and CBS pathways existed in both
      mouse bladders and SV-HUC-1 cells. H2S signaling was upregulated in PAR4-induced
      bladder pain models, and H2S-generating enzyme activity was upregulated in human
      bladders, mouse bladders, and SV-HUC-1 cells. Pretreatment with AOAA or NaHS
      inhibited or promoted PAR4-induced mechanical hyperalgesia, respectively;
      however, PAG only partially inhibited PAR4-induced bladder pain. Treatment with
      PAG or AOAA decreased H2S production in both mouse bladders and SV-HUC-1 cells.
      Pretreatment with AOAA increased MIF protein levels in bladder tissues and cells,
      whereas pretreatment with NaHS lowered MIF protein levels. Bladder pain triggered
      by the H2S pathway was not accompanied by inflammation or altered micturition
      behavior. Thus endogenous H2S generated by CBS or CSE caused referred
      hyperalgesia mediated through MIF in mice with PAR4-induced bladder pain, without
      causing bladder injury or altering micturition behavior.

PMID- 29357420
TI  - Renal Na-handling defect associated with PER1-dependent nondipping hypertension
      in male mice.
AB  - Many physiological functions have a circadian rhythm, including blood pressure
      (BP). BP is highest during the active phase, whereas during the rest period, BP
      dips 10-20%. Patients that do not experience this dip at night are termed
      "nondippers." Nondipping hypertension is associated with increased risk of
      cardiovascular disease. The mechanisms underlying nondipping hypertension are not
      understood. Without the circadian clock gene Per1, C57BL/6J mice develop
      nondipping hypertension on a high-salt diet plus mineralocorticoid treatment
      (HS/DOCP). Our laboratory has shown that PER1 regulates expression of several
      genes related to sodium (Na) transport in the kidney, including epithelial Na
      channel (ENaC) and Na chloride cotransporter (NCC). Urinary Na excretion also
      demonstrates a circadian pattern with a peak during active periods. We
      hypothesized that PER1 contributes to circadian regulation of BP via a renal Na
      handling-dependent mechanism. Na-handling genes from the distal nephron were
      inappropriately regulated in KO mice on HS/DOCP. Additionally, the night/day
      ratio of Na urinary excretion by Per1 KO mice is decreased compared with WT (4 *
      vs. 7*, P < 0.001, n = 6 per group). Distal nephron-specific Per1 KO mice also
      show an inappropriate increase in expression of Na transporter genes alphaENaC
      and NCC. These results support the hypothesis that PER1 mediates control of
      circadian BP rhythms via the regulation of distal nephron Na transport genes.
      These findings have implications for the understanding of the etiology of
      nondipping hypertension and the subsequent development of novel therapies for
      this dangerous pathophysiological condition.

PMID- 29357419
TI  - Modulation of apolipoprotein L1-microRNA-193a axis prevents podocyte
      dedifferentiation in high-glucose milieu.
AB  - The loss of podocyte (PD) molecular phenotype is an important feature of diabetic
      podocytopathy. We hypothesized that high glucose (HG) induces dedifferentiation
      in differentiated podocytes (DPDs) through alterations in the apolipoprotein
      (APO) L1-microRNA (miR) 193a axis. HG-induced DPD dedifferentiation manifested in
      the form of downregulation of Wilms' tumor 1 (WT1) and upregulation of paired box
      2 (PAX2) expression. WT1-silenced DPDs displayed enhanced expression of PAX2.
      Immunoprecipitation of DPD cellular lysates with anti-WT1 antibody revealed
      formation of WT1 repressor complexes containing Polycomb group proteins, enhancer
      of zeste homolog 2, menin, and DNA methyltransferase (DNMT1), whereas silencing
      of either WT1 or DNMT1 disrupted this complex with enhanced expression of PAX2.
      HG-induced DPD dedifferentiation was associated with a higher expression of
      miR193a, whereas inhibition of miR193a prevented DPD dedifferentiation in HG
      milieu. HG downregulated DPD expression of APOL1. miR193a-overexpressing DPDs
      displayed downregulation of APOL1 and enhanced expression of dedifferentiating
      markers; conversely, silencing of miR193a enhanced the expression of APOL1 and
      preserved DPD phenotype. Moreover, stably APOL1G0-overexpressing DPDs displayed
      the enhanced expression of WT1 but attenuated expression of miR193a; nonetheless,
      silencing of APOL1 reversed these effects. Since silencing of APOL1 enhanced
      miR193a expression as well as dedifferentiation in DPDs, it appears that
      downregulation of APOL1 contributed to dedifferentiation of DPDs through enhanced
      miR193a expression in HG milieu. Vitamin D receptor agonist downregulated
      miR193a, upregulated APOL1 expression, and prevented dedifferentiation of DPDs in
      HG milieu. These findings suggest that modulation of the APOL1-miR193a axis
      carries a potential to preserve DPD molecular phenotype in HG milieu.

PMID- 29357421
TI  - MiR-200a negatively regulates TGF-beta1-induced epithelial-mesenchymal transition
      of peritoneal mesothelial cells by targeting ZEB1/2 expression.
AB  - Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells
      was recognized as the key process of peritoneal fibrosis, which is a major cause
      of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying
      these processes remain largely unknown. In this study, we found that miR-200a was
      significantly downregulated in peritoneal tissues with fibrosis in a rat model of
      PD. In vitro, transforming growth factor (TGF)-beta1-induced EMT, identified by
      de novo expression of alpha-smooth muscle actin and a loss of E-cadherin in human
      peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR
      200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2),
      suggesting a close link between miR-200a and ZEB1/2 in TGF-beta1-induced EMT. It
      was further demonstrated that miR-200a was able to bind to the 3'UTR of ZEB1/2,
      and overexpression of miR-200a blocked TGF-beta1-induced upregulation of ZEB1/2
      and, therefore, inhibited EMT and collagen expression. In contrast,
      overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression
      in HMPCs. In conclusion, miR-200a could negatively regulate TGF-beta1-induced EMT
      by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS
      indicates the therapeutic potential of miR-200a as a treatment for peritoneal
      fibrosis associated with PD.

PMID- 29357422
TI  - Tamoxifen attenuates development of lithium-induced nephrogenic diabetes
      insipidus in rats.
AB  - Lithium is widely used in treatment of bipolar affective disorders but often
      causes nephrogenic diabetes insipidus (NDI), a disorder characterized by severe
      urinary-concentrating defects. Lithium-induced NDI is caused by lithium uptake by
      collecting duct principal cells and altered expression of aquaporin-2 (AQP2),
      which are essential for water reabsorption of tubular fluid in the collecting
      duct. Sex hormones have previously been shown to affect the regulation of AQP2,
      so we tested whether tamoxifen (TAM), a selective estrogen receptor modulator,
      would attenuate lithium-induced alterations on renal water homeostasis. Rats were
      treated for 14 days with lithium, and TAM treatment was initiated 1 wk after
      onset of lithium administration. Lithium treatment resulted in severe polyuria
      and reduced AQP2 expression, which were ameliorated by TAM. Consistent with this,
      TAM attenuated downregulation of AQP2 and increased phosphorylation of the cAMP
      responsive element-binding protein, which induced AQP2 expression in freshly
      isolated inner-medullary collecting duct suspension prepared from lithium-treated
      rats. In conclusion, TAM attenuated polyuria dose dependently and impaired urine
      concentration and downregulation of AQP2 protein expression in rats with lithium
      induced NDI. These findings suggest that TAM is likely to be a novel therapeutic
      option for lithium-induced NDI.

PMID- 29357423
TI  - Acid retention in chronic kidney disease is inversely related to GFR.
AB  - Greater H+ retention in animal models of chronic kidney disease (CKD) mediates
      faster glomerular filtration rate (GFR) decline and dietary H+ reduction slows
      eGFR decline in CKD patients with reduced eGFR and H+ retention due to the high
      acid (H+) diets of developed societies. We examined if H+ retention in CKD is
      inversely associated with estimated GFR (eGFR) using cross-sectional and
      longitudinal analysis of individuals with CKD stage 1 (>90 ml.min- 1.1.73 m-2),
      CKD stage 2 (60-89 ml/min per 1.73 m2), and CKD stage 3 (30-59 ml.min- 1.1.73 m
      2) eGFR. H+ retention was assessed using the difference between observed and
      expected plasma total CO2 2 h after 0.5 meq/kg body wt oral NaHCO3. H+ retention
      was higher in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.02) at
      baseline and 5 yr, and was higher in CKD 2 vs. CKD 1 ( P < 0.01) at 10 yr. All
      groups had lower eGFR at subsequent time points ( P < 0.01) but H+ retention was
      not different among the three time points for CKD 1. By contrast, eGFR decrease
      was associated with higher H+ retention in CKD 2 at 5 yr ( P = 0.04) and 10 yr (
      P < 0.01) and with higher H+ retention in CKD 3 at 5 yr ( P < 0.01). Yearly eGFR
      decline rate was faster in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P
      < 0.01). The data show that H+ retention is inversely associated with eGFR, with
      faster eGFR decline, and support the need for greater dietary H+ reduction
      therapy for CKD individuals with lower eGFR.

PMID- 29357424
TI  - Overweight young female kidney donors have low renal functional reserve
      postdonation.
AB  - Maintenance of adequate renal function after living kidney donation is important
      for donor outcome. Overweight donors, in particular, may have an increased risk
      for end-stage kidney disease (ESKD), and young female donors have an increased
      preeclampsia risk. Both of these risks may be associated with low postdonation
      renal functional reserve (RFR). Because we previously found that higher body mass
      index (BMI) was associated with lower postdonation RFR, we now studied the
      relationship between BMI and RFR in young female donors. RFR, the rise in
      glomerular filtration rate (GFR) (125I-iothalamate clearance) during dopamine,
      was measured in female donors (<45 yr) before and after kidney donation. Donors
      who are overweight (BMI >25) and nonoverweight donors were compared by Student's
      t-test; the association was subsequently explored with regression analysis. We
      included 105 female donors [age 41 (36-44) median(IQR)] with a BMI of 25 (22-27)
      kg/m2. Predonation GFR was 118 (17) ml/min [mean(SD)] rising to 128 (19) ml/min
      during dopamine; mean RFR was 10 (10) ml/min. Postdonation GFR was 76 (13)
      ml/min, rising to 80 (12); RFR was 4 (6) ml/min ( P < 0.001 vs. predonation). In
      overweight donors, RFR was fully lost after donation (1 ml/min vs. 10 ml/min
      predonation, P < 0.001), and BMI was inversely associated with RFR after
      donation, independent of confounders (standardized beta 0.37, P = 0.02). Reduced
      RFR might associate with the risk of preeclampsia and ESKD in kidney donors.
      Prospective studies should explore whether RFR is related to preeclampsia and
      whether BMI reduction before conception is of benefit to overweight female kidney
      donors during and after pregnancy.

PMID- 29357425
TI  - Quantitative characterization of glomerular fibrosis with magnetic resonance
      imaging: a feasibility study in a rat glomerulonephritis model.
AB  - Glomerular fibrosis occurs in the early stages of multiple renal diseases,
      including hypertensive and diabetic nephropathy. Conventional assessment of
      glomerular fibrosis relies on kidney biopsy, which is invasive and does not
      reflect physiological aspects such as blood perfusion. In this study, we sought
      to assess potential changes of cortical perfusion and microstructure at different
      degrees of glomerular fibrosis using magnetic resonance imaging (MRI). A rat
      model of glomerular fibrosis was induced by injecting anti-Thy-1 monoclonal
      antibody OX-7 to promote mesangial extracellular matrix proliferation. For six
      rats on day 5 and five rats on day 12 after the induction, we measured renal
      cortical perfusion and spin-spin relaxation time (T2) in a 3-Tesla MRI scanner.
      T2 reflects tissue microstructural changes. Glomerular fibrosis severity was
      evaluated by histological analysis and proteinuria. Four rats without fibrosis
      were included as controls. In the control rats, the periodic acid-Schiff (PAS)
      positive area was 22 +/- 1% of total glomerular tuft, which increased
      significantly to 56 +/- 12% and 45 +/- 10% in the day 5 and day 12 fibrotic
      groups, respectively ( P < 0.01). For the three groups (control, day 5, and day
      12 after OX-7 injection), cortical perfusion was 7.27 +/- 2.54, 3.78 +/- 2.17,
      and 3.32 +/- 2.62 ml.min-1.g-1, respectively, decreasing with fibrosis severity (
      P < 0.01), and cortical T2 was 75.2 +/- 4.6, 84.1 +/- 3.0, and 87.9 +/- 5.6 ms,
      respectively ( P < 0.01). In conclusion, extracellular matrix proliferation in
      glomerular mesangial cells severely diminished blood flow through the glomeruli
      and also altered cortical microstructure to increase cortical T2. The MRI
      measured parameters are proven to be sensitive markers for characterizing
      glomerular fibrosis.

PMID- 29357426
TI  - Divergent roles for kidney proximal tubule and granulocyte PAD4 in ischemic AKI.
AB  - We previously demonstrated that kidney peptidylarginine deiminase-4 (PAD4) plays
      a critical role in ischemic acute kidney injury (AKI) in mice by promoting renal
      tubular inflammation and neutrophil infiltration (Ham A, Rabadi M, Kim M, Brown
      KM, Ma Z, D'Agati V, Lee HT. Am J Physiol Renal Physiol 307: F1052-F1062, 2014).
      Although the role of PAD4 in granulocytes including neutrophils is well known, we
      surprisingly observed profound renal proximal tubular PAD4 induction after renal
      ischemia-reperfusion (I/R) injury. Here we tested the hypothesis that renal
      proximal tubular PAD4 rather than myeloid-cell lineage PAD4 plays a critical role
      in exacerbating ischemic AKI by utilizing mice lacking PAD4 in renal proximal
      tubules (PAD4ff PEPCK Cre mice) or in granulocytes (PAD4ff LysM Cre mice). Mice
      lacking renal proximal tubular PAD4 were significantly protected against ischemic
      AKI compared with wild-type (PAD4ff) mice. Surprisingly, mice lacking PAD4 in
      myeloid cells were also protected against renal I/R injury although this
      protection was less compared with renal proximal tubular PAD4-deficient mice.
      Renal proximal tubular PAD4-deficient mice had profoundly reduced renal tubular
      apoptosis, whereas myeloid-cell PAD4-deficient mice showed markedly reduced renal
      neutrophil infiltration. Taken together, our studies suggest that both renal
      proximal tubular PAD4 as well as myeloid-cell lineage PAD4 play a critical role
      in exacerbating ischemic AKI. Renal proximal tubular PAD4 appears to contribute
      to ischemic AKI by promoting renal tubular apoptosis, whereas myeloid-cell PAD4
      is preferentially involved in promoting neutrophil infiltration to the kidney and
      inflammation after renal I/R.

PMID- 29357427
TI  - Interacting hypoxia and endothelin in the diabetic kidney: therapeutic options.

PMID- 29357428
TI  - Analysis of the calcium paradox of renin secretion.
AB  - The secretion of the protease renin from renal juxtaglomerular cells is enhanced
      by subnormal extracellular calcium concentrations. The mechanisms underlying this
      atypical effect of calcium have not yet been unraveled. We therefore aimed to
      characterize the effect of extracellular calcium concentration on calcium
      handling of juxtaglomerular cells and on renin secretion in more detail. For this
      purpose, we used a combination of experiments with isolated perfused mouse
      kidneys and direct calcium measurements in renin-secreting cells in situ. We
      found that lowering of the extracellular calcium concentration led to a sustained
      elevation of renin secretion. Electron-microscopical analysis of renin-secreting
      cells exposed to subnormal extracellular calcium concentrations revealed big
      omega-shaped structures resulting from the intracellular fusion and subsequent
      emptying of renin storage vesicles. The calcium concentration dependencies as
      well as the kinetics of changes were rather similar for renin secretion and for
      renovascular resistance. Since vascular resistance is fundamentally influenced by
      myosin light chain kinase (MLCK), myosin light chain phosphatase (MLCP), and Rho
      associated protein kinase (Rho-K) activities, we examined the effects of MLCK-,
      MLCP-, and Rho-K inhibitors on renin secretion. Only MLCK inhibition stimulated
      renin secretion. Conversely, inhibition of MCLP activity lowered perfusate flow
      and strongly inhibited renin secretion, which could not be reversed by lowering
      of the extracellular calcium concentration. Renin-secreting cells and smooth
      muscle cells of afferent arterioles showed immunoreactivity of MLCK. These
      findings suggest that the inhibitory effect of calcium on renin secretion could
      be explained by phosphorylation-dependent processes under control of the MLCK.

PMID- 29357429
TI  - Sweet success? SGLT2 inhibitors and diabetes.

PMID- 29357430
TI  - Role of mitochondrial oxidative stress in modulating the expressions of
      aquaporins in obstructive kidney disease.
AB  - Downregulation of aquaporins (AQPs) in obstructive kidney disease has been well
      demonstrated with elusive mechanisms. Our previous study indicated that
      mitochondrial dysfunction played a crucial role in this process. However, it is
      still uncertain how mitochondrial dysfunction affected the AQPs in obstructive
      kidney disease. This study investigated the role of mitochondria-derived
      oxidative stress in mediating obstruction-induced downregulation of AQPs. After
      unilateral ureteral obstruction for 7 days, renal superoxide dismutase 2 (SOD2;
      mitochondria-specific SOD) was reduced by 85%. Meanwhile, AQP1, AQP2, AQP3, and
      AQP4 were remarkably downregulated as determined by Western blotting and/or
      quantitative real-time PCR. Administration of the SOD2 mimic manganese (III)
      tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP) significantly attenuated AQP2
      downregulation in line with complete blockade of thiobarbituric acid-reactive
      substances elevation, whereas the reduction of AQP1, AQP3, and AQP4 was not
      affected. The cyclooxygenase (COX)-2/prostaglandin (PG) E2 pathway has been well
      documented as a contributor of AQP reduction in obstructed kidney; thus, we
      detected the levels of COX-1/2 and microsomal prostaglandin E synthase 1 (mPGES
      1) in kidney and PGE2 secretion in urine. Significantly, MnTBAP partially
      suppressed the elevation of COX-2, mPGES-1, and PGE2. Moreover, a marked decrease
      of V2 receptor was significantly restored after MnTBAP treatment. However, the
      fibrotic response and renal tubular damage were unaffected by MnTBAP in
      obstructed kidneys. Collectively, these findings suggested an important role of
      mitochondrial oxidative stress in mediating AQP2 downregulation in obstructed
      kidney, possibly via modulating the COX-2/mPGES-1/PGE2/V2 receptor pathway.

PMID- 29357431
TI  - Vascular endothelial cell changes in postcardiac surgery acute kidney injury.
AB  - Acute kidney injury (AKI) is common complication of cardiac surgery; however, the
      phenotype of this condition is poorly defined. The aim of this study was to
      characterize changes in endothelial structure and function that underlie
      postcardiopulmonary bypass (post-CPB) AKI. Adult pigs ( n = 16) were randomized
      to undergo the following procedures ( n = 8 per group): group 1: sham operation,
      neck dissection with 2.5 h of general anesthesia; and group 2: CPB, 2.5 h of
      cardiopulmonary bypass. CPB resulted in the depletion of specific epitopes of
      glycosaminoglycans side chains of the endothelial glycocalyx: Dolichos biflorus
      agglutinin: mean difference (MD) [95% confidence interval (CI)], P value: -0.26 (
      0.42, -0.09), P = 0.0024, Triticum vulgaris (wheat germ) agglutinin: -0.83 (-1.2,
      -0.38), P = 0.0005, and Ulex europaeus agglutinin 1: -0.25 (-0.49, -0.009), P =
      0.041; endothelial membrane protein: thrombomodulin: -3.13 (-5.6, -0.65), P =
      0.02; and adherens junction: VE-cadherin: -1.06 (-1.98, -0.145), P = 0.02. CPB
      also resulted in reductions in microvascular cortical perfusion: -0.62 (-1.02, 
      0.22), P = 0.006, and increased renal cortex adenosine levels: 2.32 (0.83, 3.8),
      P = 0.0059. These changes were accompanied by significant reduction in creatinine
      clearance at 1.5 h postintervention, MD 95% CI; -51.7 (-99.7, -3.7), P = 0.037,
      and at 24 h, MD (95% CI): -47.3 (-87.7, -7.6), P = 0.023, and proteinuria
      immediately postintervention MD (95% CI): 18.79 (2.17, 35.4), P = 0.03 vs. sham.
      In our experimental CPB model, endothelial injury was associated with loss of
      autoregulation, increase in microvascular permeability, and reduced glomerular
      filtration. Interventions that promote endothelial homeostasis may have clinical
      utility in the prevention of postcardiac surgery AKI.

PMID- 29357432
TI  - In vivo three-dimensional photoacoustic imaging of the renal vasculature in
      preclinical rodent models.
AB  - Noninvasive imaging of the kidney vasculature in preclinical murine models is
      important for the assessment of renal development, studying diseases and
      evaluating new therapies but is challenging to achieve using existing imaging
      modalities. Photoacoustic imaging is a promising new technique that is
      particularly well suited to visualizing the vasculature and could provide an
      alternative to existing preclinical imaging methods for studying renal vascular
      anatomy and function. To investigate this, an all-optical Fabry-Perot-based
      photoacoustic scanner was used to image the abdominal region of mice. High
      resolution three-dimensional, noninvasive, label-free photoacoustic images of the
      mouse kidney and renal vasculature were acquired in vivo. The scanner was also
      used to visualize and quantify differences in the vascular architecture of the
      kidney in vivo due to polycystic kidney disease. This study suggests that
      photoacoustic imaging could be utilized as a novel preclinical imaging tool for
      studying the biology of renal disease.

PMID- 29357433
TI  - mCCDcl1 cells show plasticity consistent with the ability to transition between
      principal and intercalated cells.
AB  - The cortical collecting duct of the mammalian kidney plays a critical role in the
      regulation of body volume, sodium pH, and osmolarity and is composed of two
      distinct cells types, principal cells and intercalated cells. Each cell type is
      detectable in the kidney by the localization of specific transport proteins such
      as aquaporin 2 (Aqp2) and epithelial sodium channel (ENaC) in principal cells and
      V-ATPase B1 and connexin 30 (Cx30) in intercalated cells. mCCDcl1 cells have been
      widely used as a mouse principal cell line on the basis of their physiological
      characteristics. In this study, the mCCDcl1 parental cell line and three sublines
      cloned from isolated single cells (Ed1, Ed2, and Ed3) were grown on filters to
      assess their transepithelial resistance, transepithelial voltage, equivalent
      short circuit current and expression of the cell-specific markers Aqp2, ENaC, V
      ATPaseB1, and Cx30. The parental mCCDcl1 cell line presented amiloride-sensitive
      electrogenic sodium transport indicative of principal cell function; however,
      immunocytochemistry and RT-PCR showed that some cells expressed the intercalated
      cell-specific markers V-ATPase B1 and Cx30, including a subset of cells also
      positive for Aqp2 and ENaC. The three subclonal lines contained cells that were
      positive for both intercalated and principal cell-specific markers. The vertical
      transmission of both principal and intercalated cell characteristics via single
      cell cloning reveals the plasticity of mCCDcl1 cells and a direct lineage
      relationship between these two physiologically important cell types and is
      consistent with mCCDcl1 cells being precursor cells.

PMID- 29357434
TI  - Neuraminidase activity mediates IL-6 production by activated lupus-prone
      mesangial cells.
AB  - The development of nephritis is a leading cause of morbidity and mortality in
      lupus patients. Although the general pathophysiological progression of lupus
      nephritis is known, the molecular mediators and mechanisms are incompletely
      understood. Previously, we demonstrated that the glycosphingolipid (GSL)
      catabolic pathway is elevated in the kidneys of MRL/lpr lupus mice and human
      lupus patients with nephritis. Specifically, the activity of neuraminidase (NEU)
      and expression of Neu1, an enzyme in the GSL catabolic pathway is significantly
      increased. To better understand the role and mechanisms by which this pathway
      contributes to the progression of LN, we analyzed the expression and effects of
      NEU activity on the function of MRL/lpr lupus-prone mesangial cells (MCs). We
      demonstrate that NEU1 and NEU3 promote IL-6 production in MES13 MCs. Neu1
      expression, NEU activity, and IL-6 production are significantly increased in
      stimulated primary MRL/lpr lupus-prone MCs, and blocking NEU activity inhibits IL
      6 production. NEU1 and NEU3 expression overlaps IgG deposits in MCs in vitro and
      in renal sections from nephritic MRL/lpr mice. Together, our results suggest that
      NEU activity mediates IL-6 production in lupus-prone MCs possibly through an IgG
      receptor complex signaling pathway.

PMID- 29357435
TI  - Highly tamoxifen-inducible principal cell-specific Cre mice with complete
      fidelity in cell specificity and no leakiness.
AB  - An ideal inducible system should be cell specific and have absolutely no
      background recombination without induction (i.e., no leakiness), a high
      recombination rate after induction, and complete fidelity in cell specificity
      (i.e., restricted recombination exclusively in cells where the driver gene is
      expressed). However, such an ideal mouse model remains unavailable for collecting
      duct research. Here, we report a mouse model that meets these criteria. In this
      model, a cassette expressing ERT2CreERT2 ( ECE) is inserted at the ATG of the
      endogenous Aqp2 locus to disrupt Aqp2 function and to express ECE under the
      control of the Aqp2 promoter. The resulting allele is named Aqp2ECE. There was no
      indication of a significant impact of disruption of a copy of Aqp2 on renal
      function and blood pressure control in adult Aqp2ECE/+ heterozygotes. Without
      tamoxifen, Aqp2ECE did not activate a Cre-dependent red fluorescence protein
      (RFP) reporter in adult kidneys. A single injection of tamoxifen (2 mg) to adult
      mice enabled Aqp2ECE to induce robust RFP expression in the whole kidney 24 h
      postinjection, with the highest recombination efficiency of 95% in the inner
      medulla. All RFP-labeled cells expressed principal cell markers (Aqp2 and Aqp3),
      but not intercalated cell markers (V-ATPase B1B2, and carbonic anhydrase II).
      Hence, Aqp2ECE confers principal cell-specific tamoxifen-inducible recombination
      with absolutely no leakiness, high inducibility, and complete fidelity in cell
      specificity, which should be an important tool for temporospatial control of
      target genes in the principal cells and for Aqp2+ lineage tracing in adult mice.

PMID- 29357436
TI  - Mechanism for higher urine pH in normal women compared with men.
AB  - Regulation of acid-base metabolism maintains the pH of body fluids within a tight
      range. Urine pH (UpH) is also regulated under normal conditions. Median pH of 24
      h urines is ~6, but others have noted that UpH in women is higher than men, which
      has been attributed to differences in diet. If true, it would help to explain the
      fact that calcium phosphate stones, which form at higher urine pH, are much more
      common in women than in men. We studied 14 normal subjects (7 men and 7 women)
      fed identical meals in a Clinical Research Center. Urine and blood samples were
      collected during fasting and after meals. UpH of women (6.74 +/- 0.11) exceeded
      that of men (6.07 +/- 0.17) fed, but not fasting, and UpH rose significantly with
      meals in women but not men. Serum and urine total CO2 rose with meals in women
      but not men, and in women net acid excretion fell to zero during the fed period.
      In a general linear model adjusted for age, sex, and weight, net gastrointestinal
      anion uptake was the main predictor of UpH and was significantly higher in women
      (3.9 +/- 0.6) than men (1.8 +/- 0.7) in the fed period. Urine citrate, an anion
      absorbed by the gastrointestinal tract, was higher in women than men in the fed
      state, and fractional excretion of citrate was higher in women than men. The
      higher fed UpH in women is related to a greater absorption of food anions and
      raises 24-h UpH.

PMID- 29357438
TI  - Therapeutic potential of regulatory macrophages generated from peritoneal
      dialysate in adriamycin nephropathy.
AB  - Cell therapy using macrophages requires large amounts of cells, which are
      difficult to collect from patients. Patients undergoing peritoneal dialysis (PD)
      discard huge numbers of peritoneal macrophages in dialysate daily. Macrophages
      can be modulated to become regulatory macrophages, which have shown great promise
      as a therapeutic strategy in experimental kidney disease and human kidney
      transplantation. This study aimed to examine the potential of using peritoneal
      macrophages (PMs) from peritoneal dialysate to treat kidney disease.
      Monocytes/macrophages accounted for >40% of total peritoneal leukocytes in both
      patients and mice undergoing PD. PMs from patients and mice undergoing PD were
      more mature than peripheral monocytes/macrophages, as shown by low expression of
      C-C motif chemokine receptor 2 (CCR2) and morphological changes during in vitro
      culture. PMs from patients and mice undergoing PD displayed normal macrophage
      function and could be modulated into a regulatory (M2) phenotype. In vivo,
      adoptive transfer of peritoneal M2 macrophages derived from PD mice effectively
      protected against kidney injury in mice with adriamycin nephropathy (AN).
      Importantly, the transfused peritoneal M2 macrophages maintained their M2
      phenotype in kidney of AN mice. In conclusion, PMs derived from patients and mice
      undergoing PD exhibited conventional macrophage features. Peritoneal M2
      macrophages derived from PD mice are able to reduce kidney injury in AN,
      suggesting that peritoneal macrophages from patients undergoing PD may have the
      potential for clinical therapeutic application.

PMID- 29357437
TI  - Renal ischemia-reperfusion injury causes hypertension and renal perfusion
      impairment in the CD1 mice which promotes progressive renal fibrosis.
AB  - Renal ischemia-reperfusion injury (IRI) is a severe complication of major surgery
      and a risk factor for increased morbidity and mortality. Here, we investigated
      mechanisms that might contribute to IRI-induced progression to chronic kidney
      disease (CKD). Acute kidney injury (AKI) was induced by unilateral IRI for 35 min
      in CD1 and C57BL/6 (B6) mice. Unilateral IRI was used to overcome early
      mortality. Renal morphology, NGAL upregulation, and neutrophil infiltration as
      well as peritubular capillary density were studied by immunohistochemistry. The
      composition of leukocyte infiltrates in the kidney after IRI was investigated by
      flow cytometry. Systemic blood pressure was measured with a tail cuff, and renal
      perfusion was quantified by functional magnetic resonance imaging (fMRI).
      Mesangial matrix expansion was assessed by silver staining. Following IRI, CD1
      and B6 mice developed similar morphological signs of AKI and increases in NGAL
      expression, but neutrophil infiltration was greater in CD1 than B6 mice. IRI
      induced an increase in systemic blood pressure of 20 mmHg in CD1, but not in B6
      mice; and CD1 mice also had a greater loss of renal perfusion and kidney volume
      than B6 mice ( P < 0.05). CD1 mice developed substantial interstitial fibrosis
      and decreased peritubular capillary (PTC) density by day 14 while B6 mice showed
      only mild renal scarring and almost normal PTC. Our results show that after IRI,
      CD1 mice develop more inflammation, hypertension, and later mesangial matrix
      expansion than B6 mice do. Subsequently, CD1 animals suffer from CKD due to
      impaired renal perfusion and pronounced permanent loss of peritubular
      capillaries.

PMID- 29357440
TI  - Deep-sea diving into the renal transcriptome of high-fat-fed mice nets unique
      catch.

PMID- 29357439
TI  - Circadian regulation of kidney function: finding a role for Bmal1.
AB  - Mounting evidence suggests that there is an internal molecular "clock" within the
      kidney to help maintain normal renal function. Disturbance of the kidney
      circadian rhythm may pose a threat to water and electrolyte homeostasis and blood
      pressure regulation, among many other problems. The identification of circadian
      genes facilitated a more comprehensive appreciation of the importance of "keeping
      the body on time"; however, our knowledge is very limited with regard to how
      circadian genes regulate kidney function. In this brief review, we summarize
      recent progress in circadian control of renal physiology, with a particular focus
      on aryl hydrocarbon receptor nuclear translocator-like protein (Arntl1; also
      called Bmal1).

PMID- 29357441
TI  - At last! Quantitative cortical vascular anatomy.

PMID- 29357442
TI  - Characterization of urinary exosomal release of aquaporin-1 and -2 after renal
      ischemia-reperfusion in rats.
AB  - Acute kidney injury (AKI) is an important risk factor for the development of
      chronic kidney disease (CKD), and an alteration in renal water handling has been
      observed during the transition of AKI to CKD. Urinary exosomal release of
      aquaporin-1 (AQP1) and AQP2, important proteins for renal water handling, has
      recently been reported to predict their levels of renal expression. Therefore, we
      examined the patterns of urinary exosomal release of AQP1 and AQP2, and the
      exosomal marker proteins tumor susceptibility 101 protein (TSG101) and ALG-2
      interacting protein X (Alix), in the acute and chronic phases following induction
      of AKI by renal bilateral ischemia/reperfusion (I/R) in rats. Blood tests and
      histological examinations indicated that AKI occurred before at 7 days after
      renal I/R ( day 7) and that renal fibrosis developed progressively thereafter.
      Immunoblotting demonstrated significant decreases in the urinary exosomal release
      of AQP1 and AQP2 during severe AKI. Urinary exosomal release of Alix and TSG101
      was significantly increased on day 7. These data were also confirmed in rats with
      unilateral renal I/R causing more serious AKI. Urinary exosomal release of either
      the Ser-256- or Ser-269-phosphorylated form of AQP2, both of which are involved
      in apical trafficking of AQP2, was positively correlated with that of total AQP2.
      These results suggest that urinary exosomal release of AQP1 and AQP2 is reduced
      in I/R-induced AKI, whereas that of Alix and TSG101 is increased in the initial
      phase of renal fibrosis. Furthermore, apical trafficking of AQP2 appears to be
      related to urinary exosomal release of AQP2.

PMID- 29357443
TI  - Hyperfiltration, urinary albumin excretion, and ambulatory blood pressure in
      adolescents with Type 1 diabetes mellitus.
AB  - Adolescents with Type 1 diabetes mellitus (T1DM) are at risk for hyperfiltration
      and elevated urinary albumin-to-creatinine ratio (ACR), which are early
      indicators of diabetic nephropathy. Adolescents with T1DM also develop early
      changes in blood pressure, cardiovascular structure, and function. Our aims were
      to define the relationships between hyperfiltration, ACR, and 24-h ambulatory
      blood pressure over time in adolescents with T1DM. Normotensive, normoalbuminuric
      adolescents ( n = 98) with T1DM underwent baseline and 2-yr 24-h ambulatory blood
      pressure monitoring, glomerular filtration rate (eGFR) estimated by cystatin C
      (Larsson equation), and ACR measurements. Linear regression models adjusted for
      diabetes duration, sex, and HbA1c were used to determine associations.
      Hyperfiltration (eGFR >= 133 ml/min) was present in 31% at baseline and 21% at 2
      yr follow-up. Hyperfiltration was associated with greater odds of rapid GFR
      decline (>3 ml.min-1.yr-1) [OR: 5.33, 95%; CI: 1.87-15.17; P = 0.002] over 2 yr.
      Natural log of ACR at baseline was associated with greater odds of
      hyperfiltration (OR: 1.71, 95% CI: 1.00-2.92; P = 0.049) and 2-yr follow-up (OR:
      2.14, 95%; CI: 1.09-4.19; P = 0.03). One SD increase in eGFR, but not ln ACR, at
      2-yr follow-up conferred greater odds of nighttime nondipping pattern (OR: 1.96,
      95% CI: 1.06-3.63; P = 0.03). Hyperfiltration was prevalent at baseline and at 2
      yr follow-up, predicted rapid decline in GFR, and was related to ACR. Elevated
      GFR at 2-yr follow-up was associated with nighttime nondipping pattern. More work
      is needed to better understand early relationships between renal hemodynamic and
      systemic hemodynamic changes in adolescents with T1DM to reduce future
      cardiorenal complications.

PMID- 29357445
TI  - A computational model for how the fast afterhyperpolarization paradoxically
      increases gain in regularly firing neurons.
AB  - The gain of a neuron, the number and frequency of action potentials triggered in
      response to a given amount of depolarizing injection, is an important behavior
      underlying a neuron's function. Variations in action potential waveform can
      influence neuronal discharges by the differential activation of voltage- and ion
      gated channels long after the end of a spike. One component of the action
      potential waveform, the afterhyperpolarization (AHP), is generally considered an
      inhibitory mechanism for limiting firing rates. In dentate gyrus granule cells
      (DGCs) expressing fast-gated BK channels, large fast AHPs (fAHP) are
      paradoxically associated with increased gain. In this article, we describe a
      mechanism for this behavior using a computational model. Hyperpolarization
      provided by the fAHP enhances activation of a dendritic inward current (a T-type
      Ca2+ channel is suggested) that, in turn, boosts rebound depolarization at the
      soma. The model suggests that the fAHP may both reduce Ca2+ channel inactivation
      and, counterintuitively, enhance its activation. The magnitude of the rebound
      depolarization, in turn, determines the activation of a subsequent, slower inward
      current (a persistent Na+ current is suggested) limiting the interspike interval.
      Simulations also show that the effect of AHP on gain is also effective for
      physiologically relevant stimulation; varying AHP amplitude affects interspike
      interval across a range of "noisy" stimulus frequency and amplitudes. The
      mechanism proposed suggests that small fAHPs in DGCs may contribute to their
      limited excitability. NEW & NOTEWORTHY The afterhyperpolarization (AHP) is
      canonically viewed as a major factor underlying the refractory period, serving to
      limit neuronal firing rate. We recently reported that enhancing the amplitude of
      the fast AHP (fAHP) in a relatively slowly firing neuron (vs. fast spiking
      neurons) expressing fast-gated BK channels augments neuronal excitability. In
      this computational study, we present a novel, quantitative hypothesis for how
      varying the amplitude of the fAHP can, paradoxically, influence a subsequent
      spike tens of milliseconds later.

PMID- 29357444
TI  - Renal potassium handling in rats with subtotal nephrectomy: modeling and
      analysis.
AB  - We sought to decipher the mechanisms underlying the kidney's response to changes
      in K+ load and intake, under physiological and pathophysiological conditions. To
      accomplish that goal, we applied a published computational model of epithelial
      transport along rat nephrons in a sham rat, an uninephrectomized (UNX) rat, and a
      5/6-nephrectomized (5/6-NX) rat that also considers adaptations in glomerular
      filtration rate and tubular growth. Model simulations of an acute K+ load
      indicate that elevated expression levels and activities of Na+/K+-ATPase,
      epithelial sodium channels, large-conductance Ca2+-activated K+ channels, and
      renal outer medullary K+ channels, together with downregulation of sodium
      chloride cotransporters (NCC), increase K+ secretion along the connecting tubule,
      resulting in a >6-fold increase in urinary K+ excretion in sham rats, which
      substantially exceeds the filtered K+ load. In the UNX and 5/6-NX models, the
      acute K+ load is predicted to increase K+ excretion, but at significantly reduced
      levels compared with sham. Acute K+ load is accompanied by natriuresis in sham
      rats. Model simulations suggest that the lesser natriuretic effect observed in
      the nephrectomized groups may be explained by impaired NCC downregulation in
      these kidneys. At a single-nephron level, a high K+ intake raises K+ secretion
      along the connecting tubule and reabsorption along the collecting duct in sham,
      and even more in UNX and 5/6-NX. However, the increased K+ secretion per tubule
      fails to sufficiently compensate for the reduction in nephron number, such that
      nephrectomized rats have an impaired ability to excrete an acute or chronic K+
      load.

PMID- 29357447
TI  - Very small faces are easily discriminated under long and short exposure times.
AB  - Acuity measures related to overall face size that can be perceived have not been
      studied quantitatively. Consequently, experimenters use a wide range of sizes
      (usually large) without always providing a rationale for their choices. I studied
      thresholds for face discrimination by presenting both long (500 ms)- and short
      (17, 33, 50 ms)-duration stimuli. Face width threshold for the long presentation
      was ~0.2 degrees , and thresholds for the flashed stimuli ranged from ~0.3
      degrees  for the 17-ms flash to ~0.23 degrees  for the 33- and 50-ms flashes.
      Such thresholds indicate that face stimuli used in physiological or
      psychophysical experiments are often too large to tap human fine spatial
      capabilities, and thus interpretations of such experiments should take into
      account face discrimination acuity. The 0.2 degrees  threshold found in this
      study is incompatible with the prevalent view that faces are represented by a
      population of specialized "face cells" because those cells do not respond to <1
      degrees  stimuli and are optimally tuned to >4 degrees  faces. Also, the ability
      to discriminate small, high-spatial frequency flashed face stimuli is
      inconsistent with models suggesting that fixational drift transforms retinal
      spatial patterns into a temporal code. It seems therefore that the small image
      motions occurring during fixation do not disrupt our perception, because all
      relevant processing is over with before those motions can have significant
      effects. NEW & NOTEWORTHY Although face perception is central to human behavior,
      the minimally perceived face size is not known. This study shows that humans can
      discriminate very small (~0.2 degrees ) faces. Furthermore, even when flashed for
      tens of milliseconds, ~0.25 degrees  faces can be discriminated. Such fine acuity
      should impact modeling of physiological mechanisms of face perception. The
      ability to discriminate flashed faces where there is almost no eye movement
      indicates that eye drift is not essential for visibility.

PMID- 29357449
TI  - The reactive leg drop: a simple and novel sensory-motor assessment to predict
      fall risk in older individuals.
AB  - There is need for a functional ability test that appropriately assesses the rapid
      integration of the sensory and motor systems required for older adults to recover
      from a slip. The purpose of this study was to assess the efficacy and reliability
      of a novel test, the reactive leg drop, for assessing sensory-motor function in
      older adults. Fourteen young (YW; mean age = 20 yr) and 11 older women (OW; mean
      age = 76 yr) participated in this study. For each drop, the leg was passively
      moved to full extension and then released. The subjects had to recognize their
      leg was free-falling and reactively kick up as quickly as possible during varying
      sensory conditions. To assess the leg drop's reliance on proprioception, other
      proprioceptive tests (e.g., patellar tendon reflexes and balance) were separately
      performed. Leg drops performed with the eyes closed ( P = 0.011) and with a
      blocked view of the leg ( P = 0.033) showed significant differences in drop angle
      between YW and OW. Significant relationships between leg drop conditions and
      balance were observed in OW that were not present within YW. When collapsed
      across groups, reflex latency was correlated with drop angle when the eyes were
      closed. The reactive leg drop was age sensitive, reliable, and likely reliant on
      proprioception, as shown by relationships to other sensory-motor assessments,
      such as balance and the patellar reflex. Although more research is needed, we
      propose that the reactive leg drop is an effective tool to assess sensory-motor
      integration in a manner that may mimic fall recovery. NEW & NOTEWORTHY The
      reactive leg drop was age sensitive and was significantly related to other
      sensory-motor assessments. The ability to accurately assess sensory-motor
      integration may aid clinicians, practitioners, and researchers in developing new
      interventions. The reactive leg drop presented in the current study is a
      potentially effective tool to assess sensory and motor integration in a manner
      that may mimic fall recovery.

PMID- 29357450
TI  - Electrophysiological correlates of incidentally learned expectations in human
      vision.
AB  - The human visual system is remarkably sensitive to environmental regularities,
      which can facilitate behavioral performance when sensory events conform to past
      experience. The point at which prior knowledge is integrated during visual
      perception is unclear, particularly for incidentally learned associations. One
      possibility is that expectation shapes neural activity prospectively, in an
      anticipatory fashion, allowing prior knowledge to affect the earliest stages of
      sensory processing. Alternatively, cognitive processes underlying object
      recognition and conflict detection may be necessary precursors, constraining
      effects to later stages of processing. Here we used electroencephalography (EEG)
      to uncover neural activity that distinguishes between visual stimuli that match
      prior exposure and those that deviate from it. Participants identified visual
      targets that were associated with possible target locations; each location was
      associated with a high-probability target and a low-probability target. Alongside
      a behavioral cost for stimuli that had occurred infrequently at a cued location
      compared with those that had occurred frequently, we observed a focal modulation
      of the evoked EEG response at 250 ms after target onset. Relative to likely
      targets, unlikely targets evoked an enhanced negativity at midline frontal
      electrodes, and individual differences in the magnitude of this effect were
      correlated with the response time difference between likely and unlikely targets.
      In contrast, the evoked response at the latency of the P1, a correlate of early
      sensory processing, was indistinguishable for likely and unlikely targets.
      Together, these results point to postperceptual processes as a key stage at which
      experience modulates visual processing. NEW & NOTEWORTHY We combined
      electroencephalography with an incidental learning paradigm to investigate
      whether prior knowledge of environmental regularities modulates visual processing
      at early or late stages of sensory analysis. Our results reveal that modulations
      of neural activity arising at midlevel processing stages predict behavioral costs
      for unexpected stimuli rather than effects at early stages of sensory encoding.

PMID- 29357448
TI  - Propagation of beta/gamma rhythms in the cortico-basal ganglia circuits of the
      parkinsonian rat.
AB  - Much of the motor impairment associated with Parkinson's disease is thought to
      arise from pathological activity in the networks formed by the basal ganglia (BG)
      and motor cortex. To evaluate several hypotheses proposed to explain the
      emergence of pathological oscillations in parkinsonism, we investigated changes
      to the directed connectivity in BG networks following dopamine depletion. We
      recorded local field potentials (LFPs) in the cortex and basal ganglia of rats
      rendered parkinsonian by injection of 6-hydroxydopamine (6-OHDA) and in dopamine
      intact controls. We performed systematic analyses of the networks using a novel
      tool for estimation of directed interactions (nonparametric directionality, NPD).
      We used a "conditioned" version of the NPD analysis that reveals the dependence
      of the correlation between two signals on a third reference signal. We find
      evidence of the dopamine dependency of both low-beta (14-20 Hz) and high-beta/low
      gamma (20-40 Hz) directed network interactions. Notably, 6-OHDA lesions were
      associated with enhancement of the cortical "hyperdirect" connection to the
      subthalamic nucleus (STN) and its feedback to the cortex and striatum. We find
      that pathological beta synchronization resulting from 6-OHDA lesioning is widely
      distributed across the network and cannot be located to any individual structure.
      Furthermore, we provide evidence that high-beta/gamma oscillations propagate
      through the striatum in a pathway that is independent of STN. Rhythms at high
      beta/gamma show susceptibility to conditioning that indicates a hierarchical
      organization compared with those at low beta. These results further inform our
      understanding of the substrates for pathological rhythms in salient brain
      networks in parkinsonism. NEW & NOTEWORTHY We present a novel analysis of
      electrophysiological recordings in the cortico-basal ganglia network with the aim
      of evaluating several hypotheses concerning the origins of abnormal brain rhythms
      associated with Parkinson's disease. We present evidence for changes in the
      directed connections within the network following chronic dopamine depletion in
      rodents. These findings speak to the plausibility of a "short-circuiting" of the
      network that gives rise to the conditions from which pathological synchronization
      may arise.

PMID- 29357451
TI  - High-definition transcranial direct-current stimulation of the right M1 further
      facilitates left M1 excitability during crossed facilitation.
AB  - The crossed-facilitation (CF) effect refers to when motor-evoked potentials
      (MEPs) evoked in the relaxed muscles of one arm are facilitated by contraction of
      the opposite arm. The aim of this study was to determine whether high-definition
      transcranial direct-current stimulation (HD-tDCS) applied to the right primary
      motor cortex (M1) controlling the left contracting arm [50% maximum voluntary
      isometric contraction (MVIC)] would further facilitate CF toward the relaxed
      right arm. Seventeen healthy right-handed subjects participated in an anodal and
      cathodal or sham HD-tDCS session of the right M1 (2 mA for 20 min) separated by
      at least 48 h. Single-pulse transcranial magnetic stimulation (TMS) was used to
      elicit MEPs and cortical silent periods (CSPs) from the left M1 at baseline and
      10 min into and after right M1 HD-tDCS. At baseline, compared with resting, CF
      (i.e., right arm resting, left arm 50% MVIC) increased left M1 MEP amplitudes
      (+97%) and decreased CSPs (-11%). The main novel finding was that right M1 HD
      tDCS further increased left M1 excitability (+28.3%) and inhibition (+21%) from
      baseline levels during CF of the left M1, with no difference between anodal and
      cathodal HD-tDCS sessions. No modulation of CSP or MEP was observed during sham
      HD-tDCS sessions. Our findings suggest that CF of the left M1 combined with right
      M1 anodal or cathodal HD-tDCS further facilitated interhemispheric interactions
      during CF from the right M1 (contracting left arm) toward the left M1 (relaxed
      right arm), with effects on both excitatory and inhibitory processing. NEW &
      NOTEWORTHY This study shows modulation of the nonstimulated left M1 by right M1
      HD-tDCS combined with crossed facilitation, which was probably achieved through
      modulation of interhemispheric interactions.

PMID- 29357452
TI  - 3D topology of orientation columns in visual cortex revealed by functional
      optical coherence tomography.
AB  - Orientation tuning is a canonical neuronal response property of six-layer visual
      cortex that is encoded in pinwheel structures with center orientation
      singularities. Optical imaging of intrinsic signals enables us to map these
      surface two-dimensional (2D) structures, whereas lack of appropriate techniques
      has not allowed us to visualize depth structures of orientation coding. In the
      present study, we performed functional optical coherence tomography (fOCT), a
      technique capable of acquiring a 3D map of the intrinsic signals, to study the
      topology of orientation coding inside the cat visual cortex. With this technique,
      for the first time, we visualized columnar assemblies in orientation coding that
      had been predicted from electrophysiological recordings. In addition, we found
      that the columnar structures were largely distorted around pinwheel centers:
      center singularities were not rigid straight lines running perpendicularly to the
      cortical surface but formed twisted string-like structures inside the cortex that
      turned and extended horizontally through the cortex. Looping singularities were
      observed with their respective termini accessing the same cortical surface via
      clockwise and counterclockwise orientation pinwheels. These results suggest that
      a 3D topology of orientation coding cannot be fully anticipated from 2D surface
      measurements. Moreover, the findings demonstrate the utility of fOCT as an in
      vivo mesoscale imaging method for mapping functional response properties of
      cortex in the depth axis. NEW & NOTEWORTHY We used functional optical coherence
      tomography (fOCT) to visualize three-dimensional structure of the orientation
      columns with millimeter range and micrometer spatial resolution. We validated
      vertically elongated columnar structure in iso-orientation domains. The columnar
      structure was distorted around pinwheel centers. An orientation singularity
      formed a string with tortuous trajectories inside the cortex and connected
      clockwise and counterclockwise pinwheel centers in the surface orientation map.
      The results were confirmed by comparisons with conventional optical imaging and
      electrophysiological recordings.

PMID- 29357453
TI  - Motor unit discharge characteristics and walking performance of individuals with
      multiple sclerosis.
AB  - Walking performance of persons with multiple sclerosis (MS) is strongly
      influenced by the activation signals received by lower leg muscles. We examined
      the associations between force steadiness and motor unit discharge
      characteristics of lower leg muscles during submaximal isometric contractions
      with tests of walking performance and disability status in individuals who self
      reported walking difficulties due to MS. We expected that worse walking
      performance would be associated with weaker plantar flexor muscles, worse force
      steadiness, and slower motor unit discharge times. Twenty-three individuals with
      relapsing-remitting MS (56 +/- 7 yr) participated in the study. Participants
      completed one to three evaluation sessions that involved two walking tests (25-ft
      walk and 6-min walk), a manual dexterity test (grooved pegboard), health-related
      questionnaires, and measurement of strength, force steadiness, and motor unit
      discharge characteristics of lower leg muscles. Multiple regression analyses were
      used to construct models to explain the variance in measures of walking
      performance. There were statistically significant differences (effect sizes: 0.21
      0.60) between the three muscles in mean interspike interval (ISI) and ISI
      distributions during steady submaximal contractions with the plantar flexor and
      dorsiflexor muscles. The regression models explained 40% of the variance in 6-min
      walk distance and 47% of the variance in 25-ft walk time with two or three
      variables that included mean ISI for one of the plantar flexor muscles,
      dorsiflexor strength, and force steadiness. Walking speed and endurance in
      persons with relapsing-remitting MS were reduced in individuals with longer ISIs,
      weaker dorsiflexors, and worse plantar flexor force steadiness. NEW & NOTEWORTHY
      The walking endurance and gait speed of persons with relapsing-remitting multiple
      sclerosis (MS) were worse in individuals who had weaker dorsiflexor muscles and
      greater force fluctuations and longer times between action potentials discharged
      by motor units in plantar flexor muscles during steady isometric contractions.
      These findings indicate that the control of motor unit activity in lower leg
      muscles of individuals with MS is associated with their walking ability.

PMID- 29357455
TI  - Nonsinusoidal neuronal oscillations: bug or feature?
AB  - There is compiling evidence suggesting that independent neuronal ensembles are
      coordinated in time and space through cross-frequency coupling (CFC). However,
      recent studies have convincingly demonstrated that nonsinusoidal oscillations
      produce serious biases in state of the art CFC metrics. Although most of studies
      treat nonsinusoidal waves as a nuisance or just ignore them, fortunately some
      scientists are starting to exploit their neurophysiological relevance opening new
      research vistas with critical implications.

PMID- 29357456
TI  - Network disruption following mild traumatic brain injury: clinical and
      experimental research implications.
AB  - Illuminating the pathophysiological mechanisms that underlie persistent
      postconcussive symptoms following mild traumatic brain injury (mTBI) is a growing
      area of study. Alhourani et al. ( J Neurophysiol 116: 1840-1847, 2016) added to
      this emerging body of literature with their study examining default mode network
      disruption in mTBI using magnetoencephalography. The findings provided enhanced
      insight into the neural underpinnings of mTBI, which can be applied to future
      clinical and experimental research in this area.

PMID- 29357454
TI  - Corticospinal gating during action preparation and movement in the primate motor
      cortex.
AB  - During everyday actions there is a need to be able to withhold movements until
      the most appropriate time. This motor inhibition is likely to rely on multiple
      cortical and subcortical areas, but the primary motor cortex (M1) is a critical
      component of this process. However, the mechanisms behind this inhibition are
      unclear, particularly the role of the corticospinal system, which is most often
      associated with driving muscles and movement. To address this, recordings were
      made from identified corticospinal (PTN, n = 94) and corticomotoneuronal (CM, n =
      16) cells from M1 during an instructed delay reach-to-grasp task. The task
      involved the animals withholding action for ~2 s until a GO cue, after which they
      were allowed to reach and perform the task for a food reward. Analysis of the
      firing of cells in M1 during the delay period revealed that, as a population, non
      CM PTNs showed significant suppression in their activity during the cue and
      instructed delay periods, while CM cells instead showed a facilitation during the
      preparatory delay. Analysis of cell activity during movement also revealed that a
      substantial minority of PTNs (27%) showed suppressed activity during movement, a
      response pattern more suited to cells involved in withholding rather than driving
      movement. These results demonstrate the potential contributions of the M1
      corticospinal system to withholding of actions and highlight that suppression of
      activity in M1 during movement preparation is not evenly distributed across
      different neural populations. NEW & NOTEWORTHY Recordings were made from
      identified corticospinal (PTN) and corticomotoneuronal (CM) cells during an
      instructed delay task. Activity of PTNs as a population was suppressed during the
      delay, in contrast to CM cells, which were facilitated. A minority of PTNs showed
      a rate profile that might be expected from inhibitory cells and could suggest
      that they play an active role in action suppression, most likely through
      downstream inhibitory circuits.

PMID- 29357457
TI  - Neck movement but not neck position modulates skin sympathetic nerve activity
      supplying the lower limbs of humans.
AB  - We previously showed that dynamic, but not static, neck displacement modulates
      muscle sympathetic nerve activity (MSNA) to lower limbs of humans. However, it is
      not known whether dynamic neck displacement modulates skin sympathetic nerve
      activity (SSNA). Tungsten microelectrodes inserted into the common peroneal nerve
      were used to record SSNA in 5 female and 4 male subjects lying supine on a table
      that fixed their head in space but allowed trapezoidal ramp (8.1 +/- 1.2 degrees
      /s) and hold (17.5 degrees  for 53 s) or sinusoidal (35 degrees  peak to peak at
      0.33-0.46 Hz) horizontal displacement of the body about the head. SSNA recordings
      were made before, during, and after trapezoidal and sinusoidal displacements of
      the body. Spike frequency analysis of trapezoidal displacements and cross
      correlation analysis during sinusoidal displacements revealed that SSNA was not
      changed by trapezoid body-only displacement but was cyclically modulated during
      sinusoidal angular displacements (median, 95% CI: 27.9%, 19.6-48.0%). The
      magnitude of this modulation was not statistically ( P > 0.05) different from
      that of cardiac and respiratory modulation at rest (47.1%, 18.7-56.3% and 48.6%,
      28.4-59.3%, respectively) or during sinusoidal displacement (10.3%, 6.2-32.1% and
      26.9%, 13.6-43.3%, respectively). Respiratory frequency was entrained above its
      resting rate (0.26 Hz, 0.2-0.29 Hz) during sinusoidal neck displacement; there
      was no significant difference ( P > 0.05) between respiratory frequency (0.38 Hz,
      0.25-0.49 Hz) and sinusoidal displacement frequency (0.39 Hz, 0.35-0.42 Hz). This
      study provides evidence that SSNA is modulated during neck movement, raising the
      possibility that neck mechanoreceptors may contribute to the cutaneous
      vasoconstriction and sweat release associated with motion sickness. NEW &
      NOTEWORTHY This study demonstrates that dynamic, but not static, stretching of
      the neck modulates skin sympathetic nerve activity in the lower limbs.

PMID- 29357458
TI  - Transmitter release site organization can predict synaptic function at the
      neuromuscular junction.
AB  - We have investigated the impact of transmitter release site (active zone; AZ)
      structure on synaptic function by physically rearranging the individual AZ
      elements in a previously published frog neuromuscular junction (NMJ) AZ model
      into the organization observed in a mouse NMJ AZ. We have used this strategy,
      purposefully without changing the properties of AZ elements between frog and
      mouse models (even though there are undoubtedly differences between frog and
      mouse AZ elements in vivo), to directly test how structure influences function at
      the level of an AZ. Despite a similarly ordered ion channel array substructure
      within both frog and mouse AZs, frog AZs are much longer and position docked
      vesicles in a different location relative to AZ ion channels. Physiologically,
      frog AZs have a lower probability of transmitter release compared with mouse AZs,
      and frog NMJs facilitate strongly during short stimulus trains in contrast with
      mouse NMJs that depress slightly. Using our computer modeling approach, we found
      that a simple rearrangement of the AZ building blocks of the frog model into a
      mouse AZ organization could recapitulate the physiological differences between
      these two synapses. These results highlight the importance of simple AZ protein
      organization to synaptic function. NEW & NOTEWORTHY A simple rearrangement of the
      basic building blocks in the frog neuromuscular junction model into a mouse
      transmitter release site configuration predicted the major physiological
      differences between these two synapses, suggesting that transmitter release site
      structure and organization is a strong predictor of function.

PMID- 29357460
TI  - Response adaptation in the barn owl's auditory space map.
AB  - Response adaptation is the change of the firing rate of neurons induced by a
      preceding stimulus. It can be found in many sensory systems and throughout the
      auditory pathway. We investigated response adaptation in the external nucleus of
      the inferior colliculus (ICX) of barn owls ( Tyto furcata), a nocturnal bird of
      prey and specialist in sound localization. Individual neurons in the ICX
      represent locations in auditory space by maximally responding to combinations of
      interaural time and level differences (ITD and ILD). Neuronal responses were
      recorded extracellularly under ketamine-diazepam anesthesia. Response adaptation
      was observed in three double stimulation paradigms. In two paradigms, the same
      binaural parameters for both stimuli were chosen. A variation of the level of the
      second stimulus yielded a level increase sufficient to compensate for adaptation
      around 5 dB. Introducing a silent interstimulus interval (ISI) resulted in
      recovery from adaptation. The time course of recovery was followed by varying the
      ISI, and full recovery was found after an ISI of 50 ms. In a third paradigm, the
      ITD of the second stimulus was varied to investigate the representation of ITD
      under adaptive conditions. We found that adaptation led to an increased precision
      and improved selectivity while the best ITD was stable. These changes of
      representation remained for longer ISIs than were needed to recover from response
      adaptation at the best ITD. Stimuli with non-best ITDs could also induce similar
      adaptive effects if the neurons responded to these ITDs. NEW & NOTEWORTHY We
      demonstrate and characterize response adaptation in neurons of the auditory space
      map in the barn owl's midbrain with acoustic double-stimulation paradigms. An
      increase of the second level by 5 dB compensated for the observed adaptive
      effect. Recovery from adaptation was faster than in upstream nuclei of the
      auditory pathway. Our results also show that response adaptation might improve
      precision and selectivity in the representation of interaural time difference.

PMID- 29357459
TI  - Impact of light-adaptive mechanisms on mammalian retinal visual encoding at high
      light levels.
AB  - A persistent change in illumination causes light-adaptive changes in retinal
      neurons. Light adaptation improves visual encoding by preventing saturation and
      by adjusting spatiotemporal integration to increase the signal-to-noise ratio
      (SNR) and utilize signaling bandwidth efficiently. In dim light, the visual input
      contains a greater relative amount of quantal noise, and vertebrate receptive
      fields are extended in space and time to increase SNR. Whereas in bright light,
      SNR of the visual input is high, the rate of synaptic vesicle release from the
      photoreceptors is low so that quantal noise in synaptic output may limit SNR
      postsynaptically. Whether and how reduced synaptic SNR impacts spatiotemporal
      integration in postsynaptic neurons remains unclear. To address this, we measured
      spatiotemporal integration in retinal horizontal cells and ganglion cells in the
      guinea pig retina across a broad illumination range, from low to high photopic
      levels. In both cell types, the extent of spatial and temporal integration
      changed according to an inverted U-shaped function consistent with adaptation to
      low SNR at both low and high light levels. We show how a simple mechanistic model
      with interacting, opponent filters can generate the observed changes in ganglion
      cell spatiotemporal receptive fields across light-adaptive states and postulate
      that retinal neurons postsynaptic to the cones in bright light adopt low-pass
      spatiotemporal response characteristics to improve visual encoding under
      conditions of low synaptic SNR.

PMID- 29357461
TI  - Phase-amplitude coupling within the anterior thalamic nuclei during seizures.
AB  - Cross-frequency phase-amplitude coupling (cfPAC) subserves an integral role in
      the hierarchical organization of interregional neuronal communication and is also
      expressed by epileptogenic cortex during seizures. Here, we sought to
      characterize patterns of cfPAC expression in the anterior thalamic nuclei during
      seizures by studying extra-operative recordings in patients implanted with deep
      brain stimulation electrodes for intractable epilepsy. Nine seizures from two
      patients were analyzed in the peri-ictal period. CfPAC was calculated using the
      modulation index and interregional functional connectivity was indexed using the
      phase-locking value. Statistical analysis was performed within subjects on the
      basis of nonparametric permutation and corrected with Gaussian field theory. Five
      of the nine analyzed seizures demonstrated significant cfPAC. Significant cfPAC
      occurred during the pre-ictal and ictal periods in three seizures, as well as the
      postictal windows in four seizures. The preferred phase at which cfPAC occurred
      differed 1) in space, between the thalami of the epileptogenic and
      nonepileptogenic hemispheres; and 2) in time, at seizure termination. The
      anterior thalamic nucleus of the epileptogenic hemisphere also exhibited altered
      interregional phase-locking synchrony concurrent with the expression of cfPAC. By
      analyzing extraoperative recordings from the anterior thalamic nuclei, we show
      that cfPAC associated with altered interregional phase synchrony is lateralized
      to the thalamus of the epileptogenic hemisphere during seizures.
      Electrophysiological differences in cfPAC, including preferred phase of
      oscillatory interactions may be further investigated as putative targets for
      individualized neuromodulation paradigms in patients with drug-resistant
      epilepsy. NEW & NOTEWORTHY The association between fast brain activity and slower
      oscillations is an integral mechanism for hierarchical neuronal communication,
      which is also manifested in epileptogenic cortex. Our data suggest that the same
      phenomenon occurs in the anterior thalamic nuclei during seizures. Further, the
      preferred phase of modulation shows differences in space, between the
      epileptogenic and nonepileptogenic hemispheres and time, as seizures terminate.
      Our data encourage the study of cross-frequency coupling for targeted,
      individualized closed-loop stimulation paradigms.

PMID- 29357462
TI  - Neural correlate of auditory spatial attention allocation in the superior
      colliculus.
AB  - This study is the physiological complement to previous behavioral work that
      demonstrated that rhesus monkeys are able to allocate attention about the
      surrounding space based on brief, broadband auditory cues. Single-unit recordings
      were taken from the intermediate layers of the superior colliculus (iSC) while
      the subjects oriented to visual and auditory targets in the context of a cuing
      task with their heads unrestrained. The results show a correlation between
      behavioral manifestations of attention allocation, attention capture and
      inhibition of return, and modulation of target-evoked responses in single iSC
      neurons. NEW & NOTEWORTHY These results show for the first time a neural
      correlate of attention capture and inhibition of return in response to auditory
      stimuli in the superior colliculus of the head-unrestrained monkey.

PMID- 29357463
TI  - Contribution of action potentials to the extracellular field potential in the
      nucleus laminaris of barn owl.
AB  - Extracellular field potentials (EFP) are widely used to evaluate in vivo neural
      activity, but identification of multiple sources and their relative contributions
      is often ambiguous, making the interpretation of the EFP difficult. We have
      therefore analyzed a model EFP from a simple brainstem circuit with separable pre
      and postsynaptic components to determine whether we could isolate its sources.
      Our previous papers had shown that the barn owl neurophonic largely originates
      with spikes from input axons and synapses that terminate on the neurons in the
      nucleus laminaris (NL) (Kuokkanen PT, Wagner H, Ashida G, Carr CE, Kempter R. J
      Neurophysiol 104: 2274-2290, 2010; Kuokkanen PT, Ashida G, Carr CE, Wagner H,
      Kempter R. J Neurophysiol 110: 117-130, 2013; McColgan T, Liu J, Kuokkanen PT,
      Carr CE, Wagner H, Kempter R. eLife 6: e26106, 2017). To determine how much the
      postsynaptic NL neurons contributed to the neurophonic, we recorded EFP responses
      in NL in vivo. Power spectral analyses showed that a small spectral component of
      the evoked response, between 200 and 700 Hz, could be attributed to the NL
      neurons' spikes, while nucleus magnocellularis (NM) spikes dominate the EFP at
      frequencies ?1 kHz. Thus, spikes of NL neurons and NM axons contribute to the EFP
      in NL in distinct frequency bands. We conclude that if the spectral components of
      source types are different and if their activities can be selectively modulated,
      the identification of EFP sources is possible. NEW & NOTEWORTHY Extracellular
      field potentials (EFPs) generate clinically important signals, but their sources
      are incompletely understood. As a model, we have analyzed the auditory
      neurophonic in the barn owl's nucleus laminaris. There the EFP originates
      predominantly from spiking in the afferent axons, with spectral power ?1 kHz,
      while postsynaptic laminaris neurons contribute little. In conclusion, the
      identification of EFP sources is possible if they have different spectral
      components and if their activities can be modulated selectively.

PMID- 29357464
TI  - Beyond the labeled line: variation in visual reference frames from intraparietal
      cortex to frontal eye fields and the superior colliculus.
AB  - We accurately perceive the visual scene despite moving our eyes ~3 times per
      second, an ability that requires incorporation of eye position and retinal
      information. In this study, we assessed how this neural computation unfolds
      across three interconnected structures: frontal eye fields (FEF), intraparietal
      cortex (LIP/MIP), and the superior colliculus (SC). Single-unit activity was
      assessed in head-restrained monkeys performing visually guided saccades from
      different initial fixations. As previously shown, the receptive fields of most
      LIP/MIP neurons shifted to novel positions on the retina for each eye position,
      and these locations were not clearly related to each other in either eye- or head
      centered coordinates (defined as hybrid coordinates). In contrast, the receptive
      fields of most SC neurons were stable in eye-centered coordinates. In FEF, visual
      signals were intermediate between those patterns: around 60% were eye-centered,
      whereas the remainder showed changes in receptive field location, boundaries, or
      responsiveness that rendered the response patterns hybrid or occasionally head
      centered. These results suggest that FEF may act as a transitional step in an
      evolution of coordinates between LIP/MIP and SC. The persistence across cortical
      areas of mixed representations that do not provide unequivocal location labels in
      a consistent reference frame has implications for how these representations must
      be read out. NEW & NOTEWORTHY How we perceive the world as stable using mobile
      retinas is poorly understood. We compared the stability of visual receptive
      fields across different fixation positions in three visuomotor regions. Irregular
      changes in receptive field position were ubiquitous in intraparietal cortex,
      evident but less common in the frontal eye fields, and negligible in the superior
      colliculus (SC), where receptive fields shifted reliably across fixations. Only
      the SC provides a stable labeled-line code for stimuli across saccades.

PMID- 29357466
TI  - Backward walking highlights gait asymmetries in children with cerebral palsy.
AB  - To investigate how early injuries to developing motor regions of the brain affect
      different forms of gait, we compared the spatiotemporal locomotor patterns during
      forward (FW) and backward (BW) walking in children with cerebral palsy (CP).
      Bilateral gait kinematics and EMG activity of 11 pairs of leg muscles were
      recorded in 14 children with CP (9 diplegic, 5 hemiplegic; 3.0-11.1 yr) and 14
      typically developing (TD) children (3.3-11.8 yr). During BW, children with CP
      showed a significant increase of gait asymmetry in foot trajectory
      characteristics and limb intersegmental coordination. Furthermore, gait
      asymmetries, which were not evident during FW in diplegic children, became
      evident during BW. Factorization of the EMG signals revealed a comparable
      structure of the motor output during FW and BW in all groups of children, but we
      found differences in the basic temporal activation patterns. Overall, the results
      are consistent with the idea that both forms of gait share pattern generation
      control circuits providing similar (though reversed) kinematic patterns. However,
      BW requires different muscle activation timings associated with muscle modules,
      highlighting subtle gait asymmetries in diplegic children, and thus provides a
      more comprehensive assessment of gait pathology in children with CP. The findings
      suggest that spatiotemporal asymmetry assessments during BW might reflect an
      impaired state and/or descending control of the spinal locomotor circuitry and
      can be used for diagnostic purposes and as complementary markers of gait
      recovery. NEW & NOTEWORTHY Early injuries to developing motor regions of the
      brain affect both forward progression and other forms of gait. In particular,
      backward walking highlights prominent gait asymmetries in children with
      hemiplegia and diplegia from cerebral palsy and can give a more comprehensive
      assessment of gait pathology. The observed spatiotemporal asymmetry assessments
      may reflect both impaired supraspinal control and impaired state of the spinal
      circuitry.

PMID- 29357465
TI  - Modeling sources of interlaboratory variability in electrophysiological
      properties of mammalian neurons.
AB  - Patch-clamp electrophysiology is widely used to characterize neuronal electrical
      phenotypes. However, there are no standard experimental conditions for in vitro
      whole cell patch-clamp electrophysiology, complicating direct comparisons between
      data sets. In this study, we sought to understand how basic experimental
      conditions differ among laboratories and how these differences might impact
      measurements of electrophysiological parameters. We curated the compositions of
      external bath solutions (artificial cerebrospinal fluid), internal pipette
      solutions, and other methodological details such as animal strain and age from
      509 published neurophysiology articles studying rodent neurons. We found that
      very few articles used the exact same experimental solutions as any other, and
      some solution differences stem from recipe inheritance from advisor to advisee as
      well as changing trends over the years. Next, we used statistical models to
      understand how the use of different experimental conditions impacts downstream
      electrophysiological measurements such as resting potential and action potential
      width. Although these experimental condition features could explain up to 43% of
      the study-to-study variance in electrophysiological parameters, the majority of
      the variability was left unexplained. Our results suggest that there are likely
      additional experimental factors that contribute to cross-laboratory
      electrophysiological variability, and identifying and addressing these will be
      important to future efforts to assemble consensus descriptions of
      neurophysiological phenotypes for mammalian cell types. NEW & NOTEWORTHY This
      article describes how using different experimental methods during patch-clamp
      electrophysiology impacts downstream physiological measurements. We characterized
      how methodologies and experimental solutions differ across articles. We found
      that differences in methods can explain some, but not all, of the study-to-study
      variance in electrophysiological measurements. Explicitly accounting for
      methodological differences using statistical models can help correct downstream
      electrophysiological measurements for cross-laboratory methodology differences.

PMID- 29357467
TI  - When uncertain, does human self-motion decision-making fully utilize complete
      information?
AB  - When forced to choose humans often feel uncertain. Investigations of human
      perceptual decision-making often employ signal detection theory, which assumes
      that even when uncertain all available information is fully utilized. However,
      other studies have suggested or assumed that, when uncertain, human subjects
      guess totally at random, ignoring available information. When uncertain, do
      humans simply guess totally at random? Or do humans fully utilize complete
      information? Or does behavior fall between these two extremes yielding "above
      chance" performance without fully utilizing complete information? While it is
      often assumed complete information is fully utilized, even when uncertain, to our
      knowledge this has never been experimentally confirmed. To answer this question,
      we combined numerical simulations, theoretical analyses, and human studies
      performed using a self-motion direction-recognition perceptual decision-making
      task (did I rotate left or right?). Subjects were instructed to make forced
      choice binary (left/right) and trinary (left/right/uncertain) decisions when cued
      following each stimulus. Our results show that humans 1) do not guess at random
      when uncertain and 2) make binary and trinary decisions equally well. These
      findings show that humans fully utilize complete information when uncertain for
      our perceptual decision-making task. This helps unify signal detection theory and
      other models of forced-choice decision-making which allow for uncertain
      responses. NEW & NOTEWORTHY Humans make many perceptual decisions every day. But
      what if we are uncertain? While many studies assume that humans fully utilize
      complete information, other studies have suggested and/or assumed that when we're
      uncertain and forced to decide, information is not fully utilized. While humans
      tend to perform above chance when uncertain, no earlier study has tested whether
      available information is fully utilized. Our results show that humans make fully
      informed decisions even when uncertain.

PMID- 29357469
TI  - Temporal neural mechanisms underlying conscious access to different levels of
      facial stimulus contents.
AB  - An important issue facing the empirical study of consciousness concerns how the
      contents of incoming stimuli gain access to conscious processing. According to
      classic theories, facial stimuli are processed in a hierarchical manner. However,
      it remains unclear how the brain determines which level of stimulus content is
      consciously accessible when facing an incoming facial stimulus. Accordingly, with
      a magnetoencephalography technique, this study aims to investigate the temporal
      dynamics of the neural mechanism mediating which level of stimulus content is
      consciously accessible. Participants were instructed to view masked target faces
      at threshold so that, according to behavioral responses, their perceptual
      awareness alternated from consciously accessing facial identity in some trials to
      being able to consciously access facial configuration features but not facial
      identity in other trials. Conscious access at these two levels of facial contents
      were associated with a series of differential neural events. Before target
      presentation, different patterns of phase angle adjustment were observed between
      the two types of conscious access. This effect was followed by stronger phase
      clustering for awareness of facial identity immediately during stimulus
      presentation. After target onset, conscious access to facial identity, as opposed
      to facial configural features, was able to elicit more robust late positivity. In
      conclusion, we suggest that the stages of neural events, ranging from prestimulus
      to stimulus-related activities, may operate in combination to determine which
      level of stimulus contents is consciously accessed. Conscious access may thus be
      better construed as comprising various forms that depend on the level of stimulus
      contents accessed. NEW & NOTEWORTHY The present study investigates how the brain
      determines which level of stimulus contents is consciously accessible when facing
      an incoming facial stimulus. Using magnetoencephalography, we show that
      prestimulus activities together with stimulus-related activities may operate in
      combination to determine conscious face detection or identification. This finding
      is distinct from the previous notion that conscious face detection precedes
      identification and provides novel insights into the temporal dynamics of
      different levels of conscious face perception.

PMID- 29357470
TI  - The rhythmic nature of visual perception.
AB  - Our continuous perception of the world could be the result of discrete sampling,
      where individual snapshots are seamlessly fused into a coherent stream. It has
      been argued that endogenous oscillatory brain activity could provide the
      functional substrate of cortical rhythmic sampling. A new study demonstrates that
      cortical rhythmic sampling is tightly linked to the oculomotor system, thus
      providing a novel perspective on the neural network underlying top-down guided
      visual perception.

PMID- 29357468
TI  - Real-time particle filtering and smoothing algorithms for detecting abrupt
      changes in neural ensemble spike activity.
AB  - Sequential change-point detection from time series data is a common problem in
      many neuroscience applications, such as seizure detection, anomaly detection, and
      pain detection. In our previous work (Chen Z, Zhang Q, Tong AP, Manders TR, Wang
      J. J Neural Eng 14: 036023, 2017), we developed a latent state-space model, known
      as the Poisson linear dynamical system, for detecting abrupt changes in neuronal
      ensemble spike activity. In online brain-machine interface (BMI) applications, a
      recursive filtering algorithm is used to track the changes in the latent
      variable. However, previous methods have been restricted to Gaussian dynamical
      noise and have used Gaussian approximation for the Poisson likelihood. To improve
      the detection speed, we introduce non-Gaussian dynamical noise for modeling a
      stochastic jump process in the latent state space. To efficiently estimate the
      state posterior that accommodates non-Gaussian noise and non-Gaussian likelihood,
      we propose particle filtering and smoothing algorithms for the change-point
      detection problem. To speed up the computation, we implement the proposed
      particle filtering algorithms using advanced graphics processing unit computing
      technology. We validate our algorithms, using both computer simulations and
      experimental data for acute pain detection. Finally, we discuss several important
      practical issues in the context of real-time closed-loop BMI applications. NEW &
      NOTEWORTHY Sequential change-point detection is an important problem in closed
      loop neuroscience experiments. This study proposes novel sequential Monte Carlo
      methods to quickly detect the onset and offset of a stochastic jump process that
      drives the population spike activity. This new approach is robust with respect to
      spike sorting noise and varying levels of signal-to-noise ratio. The GPU
      implementation of the computational algorithm allows for parallel processing in
      real time.

PMID- 29357471
TI  - Predictive monitoring of actions, EEG recordings in virtual reality.
AB  - Error-related negativity (ERN) is a signal that is associated with error
      detection. Joch and colleagues (Joch M, Hegele M, Maurer H, Muller H, Maurer LK.
      J Neurophysiol 118: 486-495, 2017) successfully separated the ERN as a response
      to online prediction error from feedback updates. We discuss the role of ERN in
      action and suggest insights from virtual reality techniques; we consider the
      potential benefit of self-evaluation in determining the mechanisms of ERN
      amplitude; finally, we review the oscillatory activity that has been claimed to
      accompany ERN.

PMID- 29357472
TI  - Age-related erosion of obstacle avoidance reflexes evoked with electrical
      stimulation of tibial nerve during walking.
AB  - In young healthy adults, characteristic obstacle avoidance reflexes have been
      demonstrated in response to electrical stimulation of cutaneous afferents of the
      foot during walking. It is unknown whether there is an age-related erosion of
      this obstacle avoidance reflex evoked with stimulation to the tibial nerve
      innervating the sole of the foot. The purpose of this study was to identify age
      dependent differences in obstacle avoidance reflexes evoked with electrical
      stimulation of the tibial nerve at the ankle during walking in healthy young and
      older (70 yr and older) adults with no history of falls. Toe clearance, ankle and
      knee joint displacement and angular velocity, and electromyograms (EMG) of the
      tibialis anterior, medial gastrocnemius, biceps femoris, and vastus lateralis
      were measured. A significant erosion of kinematic and EMG obstacle avoidance
      reflexes was seen in the older adults compared with the young. Specifically,
      during swing phase, there was reduced toe clearance, ankle dorsiflexion, and knee
      flexion angular displacement in older adults compared with the young as well as
      changes in muscle activation. These degraded reflexes were superimposed on
      altered kinematics seen during unperturbed walking in the older adults including
      reduced toe clearance and knee flexion and increased ankle dorsiflexion compared
      with the young. Notably, during mid-swing the toe clearance was reduced in the
      older adults compared with the young by 2 cm overall, resulting from a
      combination of 1-cm reduced reflex response in the older adults superimposed on 1
      cm less toe clearance during unperturbed walking. Together, these age-related
      differences could represent the prodromal phase of fall risk. NEW & NOTEWORTHY
      This study demonstrated age-dependent erosion of obstacle avoidance reflexes
      evoked with electrical stimulation of the tibial nerve at the ankle during
      walking. There was significant reduction in toe clearance, ankle dorsiflexion,
      and knee flexion reflexes as well as changes in muscle activation during swing
      phase in older adults with no history of falls compared with the young. These
      degraded reflexes, superimposed on altered kinematics seen during unperturbed
      walking, likely represent the prodromal phase of fall risk.

PMID- 29357475
TI  - Location and phase effects for ocular and cervical vestibular-evoked myogenic
      potentials evoked by bone-conducted stimuli at midline skull sites.
AB  - Our object was to investigate the effect of location and phase on the properties
      of oVEMPs and cVEMPs evoked by two bone conducted (BC) stimuli, 500 Hz and an
      impulsive stimulus for midline skull sites from Nz to Iz, in normal volunteers.
      Compressive and rarefactive onset phases were used and the induced linear and
      rotational accelerations measured. We confirmed our previous finding of marked
      changes in the polarity of oVEMPs with location. For cVEMPs using the 500Hz
      stimulus there were few changes with location or phase, but the impulsive
      stimulus showed clear phase-related changes at several locations, with the
      shortest latencies occurring with compressive stimuli at AFz and Fz and the
      largest amplitudes at Iz. For oVEMPs, both stimuli showed clear effects of phase,
      with the shortest latencies with compressive stimuli at AFz and Fz and with the
      largest negativity at Oz or Iz. Whereas the effectiveness at Iz is consistent
      with a role in the linear VOR, the inversion of polarity and shorter latency
      around AFz and Fz is not and could not be explained by changes in acceleration of
      the head. The latency for BC 500Hz oVEMPs for AFz was the same as that for air
      conducted (AC) stimuli. We suggest that whereas BC stimuli at most sites work
      through displacement of the otolith membrane, BC oVEMPs evoked at AFz and Fz may
      work through a direct action on utricular hair cells. Our findings have
      implications for clinical testing of VEMPs using midline BC stimuli. NEW &
      NOTEWORTHY We investigated VEMPs evoked from multiple midline skull sites. Large
      oVEMP responses were obtained with compressive stimuli at Iz, consistent with a
      role in the linear VOR, but we also showed inversion of polarity and the shortest
      latency for stimuli given at AFz and Fz. We propose that BC stimuli given at AFz
      and Fz may have a direct effect on otolith hair cells, whereas at other sites
      they work through displacement of the otolith membrane.

PMID- 29357473
TI  - Bayesian quantification of sensory reweighting in a familial bilateral vestibular
      disorder (DFNA9).
AB  - DFNA9 is a rare progressive autosomal dominantly inherited vestibulo-cochlear
      disorder, resulting in a homogeneous group of patients with hearing impairment
      and bilateral vestibular function loss. These patients suffer from a deteriorated
      sense of spatial orientation, leading to balance problems in darkness, especially
      on irregular surfaces. Both behavioral and functional imaging studies suggest
      that the remaining sensory cues could compensate for the loss of vestibular
      information. A thorough model-based quantification of this reweighting in
      individual patients is, however, missing. Here we psychometrically examined the
      individual patient's sensory reweighting of these cues after complete vestibular
      loss. We asked a group of DFNA9 patients and healthy control subjects to judge
      the orientation (clockwise or counterclockwise relative to gravity) of a rod
      presented within an oriented square frame (rod-in-frame task) in three different
      head-on-body tilt conditions. Our results show a cyclical frame-induced bias in
      perceived gravity direction across a 90 degrees  range of frame orientations. The
      magnitude of this bias was significantly increased in the patients compared with
      the healthy control subjects. Response variability, which increased with head-on
      body tilt, was also larger for the patients. Reverse engineering of the
      underlying signal properties, using Bayesian inference principles, suggests a
      reweighting of sensory signals, with an increase in visual weight of 20-40% in
      the patients. Our approach of combining psychophysics and Bayesian reverse
      engineering is the first to quantify the weights associated with the different
      sensory modalities at an individual patient level, which could make it possible
      to develop personal rehabilitation programs based on the patient's sensory weight
      distribution. NEW & NOTEWORTHY It has been suggested that patients with
      vestibular deficits can compensate for this loss by increasing reliance on other
      sensory cues, although an actual quantification of this reweighting is lacking.
      We combine experimental psychophysics with a reverse engineering approach based
      on Bayesian inference principles to quantify sensory reweighting in individual
      vestibular patients. We discuss the suitability of this approach for developing
      personal rehabilitation programs based on the patient's sensory weight
      distribution.

PMID- 29357474
TI  - The influence of acute elevations in plasma osmolality and serum sodium on
      sympathetic outflow and blood pressure responses to exercise.
AB  - Elevated plasma osmolality (pOsm) has been shown to increase resting sympathetic
      nerve activity in animals and humans. The present study tested the hypothesis
      that increases in pOsm and serum sodium (sNa+) concentration would exaggerate
      muscle sympathetic nerve activity (MSNA) and blood pressure (BP) responses to
      handgrip (HG) exercise and postexercise ischemia (PEI). BP and MSNA were measured
      during HG followed by PEI before and after a 23-min hypertonic saline infusion
      (HSI-3% NaCl). Eighteen participants (age 23 +/- 1 yr; BMI 24 +/- 1 kg/m2)
      completed the protocol; pOsm and sNa+ increased from pre- to post-HSI (285 +/- 1
      to 291 +/- 1 mosmol/kg H2O; 138.2 +/- 0.3 to 141.3 +/- 0.4 mM; P < 0.05 for
      both). Resting mean BP (90 +/- 2 vs. 92 +/- 1 mmHg) and MSNA (11 +/- 2 vs. 15 +/-
      2 bursts/min) were increased pre- to post-HSI ( P < 0.05 for both). Mean BP
      responses to HG (106 +/- 2 vs. 111 +/- 2 mmHg, P < 0.05) and PEI (102 +/- 2 vs.
      107 +/- 2 mmHg, P < 0.05) were higher post-HSI. Similarly, MSNA during HG (20 +/-
      2 vs. 29 +/- 2 bursts/min, P < 0.05) and PEI (19 +/- 2 vs. 24 +/- 3 bursts/min, P
      < 0.05) were greater post-HSI. In addition, the change in MSNA was greater post
      HSI during HG (Delta9 +/- 2 vs. Delta13 +/- 3 bursts/min, P < 0.05). A second set
      of participants ( n = 13, age 23 +/- 1 yr; BMI 24 +/- 1 kg/m2) completed a time
      control (TC) protocol consisting of quiet rest instead of an infusion. The TC
      condition yielded no change in resting sNa+, pOsm, mean BP, or MSNA (all P >
      0.05); responses to HG and PEI were not different pre- to post-quiet rest ( P >
      0.05). In summary, acutely increasing pOsm and sNa+ exaggerates BP and MSNA
      responses during HG exercise and PEI. NEW & NOTEWORTHY Elevated plasma osmolality
      has been shown to increase resting sympathetic activity and blood pressure. This
      study provides evidence that acute elevations in plasma osmolality and serum
      sodium exaggerated muscle sympathetic nerve activity and blood pressure responses
      during exercise pressor reflex activation in healthy young adults.

PMID- 29357476
TI  - Robust and tunable bursting requires slow positive feedback.
AB  - We highlight that the robustness and tunability of a bursting model critically
      rely on currents that provide slow positive feedback to the membrane potential.
      Such currents have the ability to make the total conductance of the circuit
      negative in a timescale that is termed "slow" because it is intermediate between
      the fast timescale of the spike upstroke and the ultraslow timescale of even
      slower adaptation currents. We discuss how such currents can be assessed either
      in voltage-clamp experiments or in computational models. We show that, while
      frequent in the literature, mathematical and computational models of bursting
      that lack the slow negative conductance are fragile and rigid. Our results
      suggest that modeling the slow negative conductance of cellular models is
      important when studying the neuromodulation of rhythmic circuits at any broader
      scale. NEW & NOTEWORTHY Nervous system functions rely on the modulation of
      neuronal activity between different rhythmic patterns. The mechanisms of this
      modulation are still poorly understood. Using computational modeling, we show the
      critical role of currents that provide slow negative conductance, distinct from
      the fast negative conductance necessary for spike generation. The significance of
      the slow negative conductance for neuromodulation is often overlooked, leading to
      computational models that are rigid and fragile.

PMID- 29357478
TI  - A new role for the exhaled nitric oxide as a functional marker of peripheral
      airway caliber changes: a theoretical study.
AB  - Although considered as an inflammation marker, exhaled nitric oxide (FENO) was
      shown to be sensitive to airway caliber changes to such an extent that it might
      be considered as a marker of them. It is thus important to understand how these
      changes and their localization mechanically affect the total NO flux penetrating
      the airway lumen ( JawNO), and hence FENO, independently from any inflammatory
      status change. In this work, a new model was used. It simulates NO production,
      consumption, and diffusion inside the airway epithelium, NO excretion from the
      epithelial wall into the airway lumen and, finally, its axial transport by
      diffusion and convection in the airway lumen. This model may also consider the
      possible presence of a fluid layer coating the epithelial wall. Simulations were
      performed. They show the great sensitivity of JawNO to peripheral airway caliber
      changes. Moreover, FENO shows distinct behaviors, depending on the location of
      the caliber change. Considering a bronchodilation, absence of FENO change was
      associated with dilation of central airways, FENO increase with dilation down to
      pre-acinar small airways, and FENO decrease with intra-acinar dilation due to the
      amplification of the back diffusion flux. The presence of a fluid layer was also
      shown to play a significant role in FENO changes. Altogether, the present work
      theoretically supports that specific FENO changes in acute situations are linked
      to specifically located airway caliber changes in the lung periphery. This opens
      the way for a new role for FENO as a functional marker of peripheral airway
      caliber change. NEW & NOTEWORTHY Using a new model of nitric oxide production and
      transport, allowing realistic simulation of airway caliber change, the present
      work theoretically supports that specific changes of the molar fraction of nitric
      oxide in the exhaled air, occurring without any change in the inflammatory
      status, are linked to specifically located airway caliber changes in the lung
      periphery. This opens the way for a new role for FENO as a functional marker of
      peripheral airway caliber change.

PMID- 29357477
TI  - Emergent coordination underlying learning to reach to grasp with a brain-machine
      interface.
AB  - The development of coordinated reach-to-grasp movement has been well studied in
      infants and children. However, the role of motor cortex during this development
      is unclear because it is difficult to study in humans. We took the approach of
      using a brain-machine interface (BMI) paradigm in rhesus macaques with prior
      therapeutic amputations to examine the emergence of novel, coordinated reach to
      grasp. Previous research has shown that after amputation, the cortical area
      previously involved in the control of the lost limb undergoes reorganization, but
      prior BMI work has largely relied on finding neurons that already encode specific
      movement-related information. In this study, we taught macaques to cortically
      control a robotic arm and hand through operant conditioning, using neurons that
      were not explicitly reach or grasp related. Over the course of training,
      stereotypical patterns emerged and stabilized in the cross-covariance between the
      reaching and grasping velocity profiles, between pairs of neurons involved in
      controlling reach and grasp, and to a comparable, but lesser, extent between
      other stable neurons in the network. In fact, we found evidence of this
      structured coordination between pairs composed of all combinations of neurons
      decoding reach or grasp and other stable neurons in the network. The degree of
      and participation in coordination was highly correlated across all pair types.
      Our approach provides a unique model for studying the development of novel,
      coordinated reach-to-grasp movement at the behavioral and cortical levels. NEW &
      NOTEWORTHY Given that motor cortex undergoes reorganization after amputation, our
      work focuses on training nonhuman primates with chronic amputations to use
      neurons that are not reach or grasp related to control a robotic arm to reach to
      grasp through the use of operant conditioning, mimicking early development. We
      studied the development of a novel, coordinated behavior at the behavioral and
      cortical level, and the neural plasticity in M1 associated with learning to use a
      brain-machine interface.

PMID- 29357479
TI  - Motoneuron excitability of the quadriceps decreases during a fatiguing submaximal
      isometric contraction.
AB  - During fatiguing voluntary contractions, the excitability of motoneurons
      innervating arm muscles decreases. However, the behavior of motoneurons
      innervating quadriceps muscles is unclear. Findings may be inconsistent because
      descending cortical input influences motoneuron excitability and confounds
      measures during exercise. To overcome this limitation, we examined effects of
      fatigue on quadriceps motoneuron excitability tested during brief pauses in
      descending cortical drive after transcranial magnetic stimulation (TMS).
      Participants ( n = 14) performed brief (~5-s) isometric knee extension
      contractions before and after a 10-min sustained contraction at ~25% maximal
      electromyogram (EMG) of vastus medialis (VM) on one ( n = 5) or two ( n = 9)
      days. Electrical stimulation over thoracic spine elicited thoracic motor evoked
      potentials (TMEP) in quadriceps muscles during ongoing voluntary drive and 100 ms
      into the silent period following TMS (TMS-TMEP). Femoral nerve stimulation
      elicited maximal M-waves (Mmax). On the 2 days, either large (~50% Mmax) or small
      (~15% Mmax) TMS-TMEPs were elicited. During the 10-min contraction, VM EMG was
      maintained ( P = 0.39), whereas force decreased by 52% (SD 13%) ( P < 0.001).
      TMEP area remained unchanged ( P = 0.9), whereas large TMS-TMEPs decreased by 49%
      (SD 28%) ( P = 0.001) and small TMS-TMEPs by 71% (SD 22%) ( P < 0.001). This
      decline was greater for small TMS-TMEPs ( P = 0.019; n = 9). Therefore, without
      the influence of descending drive, quadriceps TMS-TMEPs decreased during fatigue.
      The greater reduction for smaller responses, which tested motoneurons that were
      most active during the contraction, suggests a mechanism related to repetitive
      activity contributes to reduced quadriceps motoneuron excitability during
      fatigue. By contrast, the unchanged TMEP suggests that ongoing drive compensates
      for altered motoneuron excitability. NEW & NOTEWORTHY We provide evidence that
      the excitability of quadriceps motoneurons decreases with fatigue. Our results
      suggest that altered intrinsic properties brought about by repetitive activation
      of the motoneurons underlie their decreased excitability. Furthermore, we note
      that testing during voluntary contraction may not reflect the underlying
      depression of motoneuron excitability because of compensatory changes in ongoing
      voluntary drive. Thus, this study provides evidence that processes intrinsic to
      the motoneuron contribute to muscle fatigue of the knee extensors.

PMID- 29357480
TI  - No evidence for direct effects of recombinant human erythropoietin on cerebral
      blood flow and metabolism in healthy humans.
AB  - Erythropoietin (EPO) is expressed in human brain tissue, but its exact role is
      unknown. EPO may improve the efficiency of oxidative metabolism and has
      neuroprotective properties against hypoxic injuries in animal models. We aimed to
      investigate the effect of recombinant human EPO (rHuEPO) administration on
      healthy cerebral metabolism in humans during normoxia and during metabolic stress
      by inhalation of 10% O2 hypoxic air. Twenty-four healthy men participated in a
      two-arm double-blind placebo-controlled trial. rHuEPO was administered as a low
      dose (5,000 IU) over 4 wk ( n = 12) or as a high dose (500 IU.kg body wt-1.day-1)
      for three consecutive days ( n = 12). Global cerebral blood flow (CBF) and
      metabolic rate of glucose (CMRglc) were measured with positron emission
      tomography. CBF, metabolic rate of oxygen ([Formula: see text]), and cerebral
      lactate concentration were measured by magnetic resonance imaging and
      spectroscopy. Low-dose treatment increased hemoglobin and was associated with a
      near-significant decrease in CBF during baseline normoxia. High-dose treatment
      caused no change in CBF. Neither treatment had an effect on normoxia CMRglc,
      [Formula: see text], or lactate concentration or an effect on the cerebral
      metabolic response to inhalation of hypoxic air. In conclusion, the study found
      no evidence for a direct effect of rHuEPO on cerebral metabolism. NEW &
      NOTEWORTHY We demonstrate with magnetic resonance imaging and positron emission
      tomography that administration of erythropoietin does not have a substantial
      direct effect on healthy human resting cerebral blood flow or effect on cerebral
      glucose and oxygen metabolism. Also, administration of erythropoietin did not
      have a direct effect on the metabolic response to acute hypoxic stress in healthy
      humans, and a suggested neuroprotective effect from erythropoietin is therefore
      likely not a direct effect of erythropoietin on cerebral metabolism.

PMID- 29357481
TI  - Repeated testing for the assessment of individual response to exercise training.
AB  - Observed response to regular exercise training differs widely between individuals
      even in tightly controlled research settings. However, the respective
      contributions of random error and true interindividual differences as well as the
      relative frequency of nonresponders are disputed. Specific challenges of analyses
      on the individual level as well as a striking heterogeneity in definitions may
      partly explain these inconsistent results. Repeated testing during the training
      phase specifically addresses the requirements of analyses on the individual
      level. Here we report a first implementation of this innovative design amendment
      in a head-to-head comparison of existing analytical approaches. To allow for
      comparative implementation of approaches we conducted a controlled endurance
      training trial (1 yr walking/jogging, 3 days/wk for 45 min with 60% heart rate
      reserve) in healthy, untrained subjects ( n = 36, age = 46 +/- 8 yr; body mass
      index 24.7 +/- 2.7 kg/m2; Vo2max 36.6 +/- 5.4). In the training group additional
      Vo2max tests were conducted after 3, 6, and 9 mo. Duration of the control
      condition was 6 mo due to ethical constraints. General efficacy of the training
      intervention could be verified by a significant increase in Vo2max in the
      training group ( P < 0.001 vs. control). Individual training response of relevant
      magnitude (>0.2 * baseline variability in Vo2max) could be demonstrated by
      several approaches. Regarding the classification of individuals, only 11 of 20
      subjects were consistently classified, demonstrating remarkable disagreement
      between approaches. These results are in support of relevant interindividual
      variability in training efficacy and stress the limitations of a responder
      classification. Moreover, this proof-of-concept underlines the need for tailored
      methodological approaches for well-defined problems. NEW & NOTEWORTHY This work
      reports a first implementation of a repeated testing training trial for the
      investigation of individual response. This design amendment was recently proposed
      to address specifically the statistical requirements of analyses on the
      individual level. Moreover, a comprehensive comparison of previously published
      methods exemplifies the striking heterogeneity of existing approaches.

PMID- 29357482
TI  - Prior acetaminophen consumption impacts the early adaptive cellular response of
      human skeletal muscle to resistance exercise.
AB  - Resistance exercise (RE) is a powerful stimulus for skeletal muscle adaptation.
      Previous data demonstrate that cyclooxygenase (COX)-inhibiting drugs alter the
      cellular mechanisms regulating the adaptive response of skeletal muscle. The
      purpose of this study was to determine whether prior consumption of the COX
      inhibitor acetaminophen (APAP) alters the immediate adaptive cellular response in
      human skeletal muscle after RE. In a double-blinded, randomized, crossover
      design, healthy young men ( n = 8, 25 +/- 1 yr) performed two trials of
      unilateral knee extension RE (8 sets, 10 reps, 65% max strength). Subjects
      ingested either APAP (1,000 mg/6 h) or placebo (PLA) for 24 h before RE (final
      dose consumed immediately after RE). Muscle biopsies (vastus lateralis) were
      collected at rest and 1 h and 3 h after exercise. Mammalian target of rapamycin
      (mTOR) complex 1 signaling was assessed through immunoblot and
      immunohistochemistry, and mRNA expression of myogenic genes was examined via RT
      qPCR. At 1 h p-rpS6Ser240/244 was increased in both groups but to a greater
      extent in PLA. At 3 h p-S6K1Thr389 was elevated only in PLA. Furthermore,
      localization of mTOR to the lysosome (LAMP2) in myosin heavy chain (MHC) II
      fibers increased 3 h after exercise only in PLA. mTOR-LAMP2 colocalization in MHC
      I fibers was greater in PLA vs. APAP 1 h after exercise. Myostatin mRNA
      expression was reduced 1 h after exercise only in PLA. MYF6 mRNA expression was
      increased 1 h and 3 h after exercise only in APAP. APAP consumption appears to
      alter the early adaptive cellular response of skeletal muscle to RE. These
      findings further highlight the mechanisms through which COX-inhibiting drugs
      impact the adaptive response of skeletal muscle to exercise. NEW & NOTEWORTHY The
      extent to which the cellular reaction to acetaminophen impacts the mechanisms
      regulating the adaptive response of human skeletal muscle to resistance exercise
      is not well understood. Consumption of acetaminophen before resistance exercise
      appears to suppress the early response of mTORC1 activity to acute resistance
      exercise. These data also demonstrate, for the first time, that resistance
      exercise elicits fiber type-specific changes in the intracellular colocalization
      of mTOR with the lysosome in human skeletal muscle.

PMID- 29357483
TI  - Successive contractile periods activate mitochondria at the onset of contractions
      in intact rat cardiac trabeculae.
AB  - The rate of oxidative phosphorylation depends on the contractile activity of the
      heart. Cardiac mitochondrial oxidative phosphorylation is determined by free ADP
      concentration, mitochondrial Ca2+ accumulation, mitochondrial enzyme activities,
      and Krebs cycle intermediates. The purpose of the present study was to examine
      the factors that limit oxidative phosphorylation upon rapid changes in
      contractile activity in cardiac muscle. We tested the hypotheses that prior
      contractile performance enhances the changes in NAD(P)H and FAD concentration
      upon an increase in contractile activity and that this mitochondrial "priming"
      depends on pyruvate dehydrogenase activity. Intact rat cardiac trabeculae were
      electrically stimulated at 0.5 Hz for at least 30 min. Thereafter, two equal
      bouts at elevated stimulation frequency of 1, 2, or 3 Hz were applied for 3 min
      with 3 min of 0.5-Hz stimulation in between. No discernible time delay was
      observed in the changes in NAD(P)H and FAD fluorescence upon rapid changes in
      contractile activity. The amplitudes of the rapid changes in fluorescence upon an
      increase in stimulation frequency (the on-transients) were smaller than upon a
      decrease in stimulation frequency (the off-transients). A first bout in glucose
      containing superfusion solution resulted, during the second bout, in an increase
      in the amplitudes of the on-transients, but the off-transients remained the same.
      No such priming effect was observed after addition of 10 mM pyruvate. These
      results indicate that mitochondrial priming can be observed in cardiac muscle in
      situ and that pyruvate dehydrogenase activity is critically involved in the
      mitochondrial adaptation to increases in contractile performance. NEW &
      NOTEWORTHY Mitochondrial respiration increases with increased cardiac contractile
      activity. Similar to mitochondrial "priming" in skeletal muscle, we hypothesized
      that cardiac mitochondrial activity is altered upon successive bouts of
      contractions and depends on pyruvate dehydrogenase activity. We found altered
      bioenergetics upon repeated contractile periods, indicative of mitochondrial
      priming in rat myocardium. No effect was seen when pyruvate was added to the
      perfusate. As such, pyruvate dehydrogenase activity is involved in the
      mitochondrial adaptation to increased contractile performance.

PMID- 29357484
TI  - A new cover and updated scope for the Journal of Applied Physiology.

PMID- 29357485
TI  - Chest wall strapping increases expiratory airflow and detectable airway segments
      in computer tomographic scans of normal and obstructed lungs.
AB  - Chest wall strapping (CWS) induces breathing at low lung volumes but also
      increases parenchymal elastic recoil. In this study, we tested the hypothesis
      that CWS dilates airways via airway-parenchymal interdependence. In 11 subjects
      (6 healthy and 5 with mild to moderate COPD), pulmonary function tests and lung
      volumes were obtained in control (baseline) and the CWS state. Control and CWS-CT
      scans were obtained at 50% of control (baseline) total lung-capacity (TLC). CT
      lung volumes were analyzed by CT volumetry. If control and CWS-CT volumetry did
      not differ by more than 25%, airway dimensions were analyzed via automated airway
      segmentation. CWS-TLC was reduced on average to 71% of control-TLC in normal
      subjects and 79% of control-TLC in subjects with COPD. CWS increased expiratory
      airflow at 50% of control-TLC by 41% (3.50 +/- 1.6 vs. 4.93 +/- 1.9 l/s, P =
      0.04) in normals and 316% in COPD(0.25 +/- 0.05 vs 0.79 +/- 0.39 l/s, P = 0.04).
      In 10 subjects (5 normals and 5 COPD), control and CWS-CT scans at 50% control
      TLC did not differ more than 25% on CT volumetry and were included in the airway
      structure analysis. CWS increased the mean number of detectable airways with a
      diameter of <=2 mm by 32.5% (65 +/- 10 vs. 86 +/- 124, P = 0.01) in normal
      subjects and by 79% (59 +/- 19 vs. 104 +/- 16, P = 0.01) in subjects with COPD.
      There was no difference in the number of detectable airways with diameters 2-4 mm
      and >4 mm in normal or in COPD subjects. In conclusion, CWS enhances the
      detection of small airways via automated CT airway segmentation and increases
      expiratory airflow in normal subjects as well as in subjects with mild to
      moderate COPD. NEW & NOTEWORTHY In normal and COPD subjects, chest wall
      strapping(CWS) increased the number of detectable small airways using automated
      CT airway segmentation. The concept of dysanapsis expresses the physiological
      variation in the geometry of the tracheobronchial tree and lung parenchyma based
      on development. We propose a dynamic concept to dysanapsis in which CWS leads to
      breathing at lower lung volumes with a corresponding increase in the size of
      small airways, a potentially novel, nonpharmacological treatment for COPD.

PMID- 29357486
TI  - Evolution of Ventricular Hypertrophy and Myocardial Mechanics in Physiologic and
      Pathologic Hypertrophy.
AB  - LEFT VENTRICULAR HYPERTROPHY (LVH) is an adaptive response to physiologic or
      pathologic stimuli and distinguishing between the two has obvious clinical
      implications. However, asymmetric septal hypertrophy and preserved cardiac
      function are noted in early stages in both cases. We characterized the early
      anatomic and functional changes in a mouse model of physiologic and pathologic
      stress using serial echocardiography-based morphometry and tissue velocity
      imaging. Weight-matched CF-1 male mice were separated into CONTROLS (n=10),
      treadmill EXERCISE 1 hour daily x 5 days/week (n=7) and transverse aortic
      constriction (TAC, n=7). Hypertrophy was noted first in the LV basal septum
      compared to other segments in EXERCISE (0.84+/-0.02 vs. 0.79+/-0.03 mm, p=0.03)
      and TAC (0.86+/-0.05 vs. 0.77+/-0.04 mm, p=0.02) at 4 and 3 weeks, respectively.
      At 8 weeks, eccentric LVH was noted in EXERCISE and concentric LVH in TAC. Septal
      E/E' ratio increased in TAC (32.6+/-3.7 vs. 37+/-6.2, p=0.002) compared with the
      CONTROLS and EXERCISE (32.3+/-5.2 vs. 32.8+/-3.8 and 31.2+/-4.9 vs. 28.2+/-5.0,
      respectively, non-significant for both). Septal s' decreased in TAC (21+/-3.6 vs.
      17+/-4.2 cm/s, p=0.04) but increased in EXERCISE (19.6+/-4.1 vs. 29.2+/-2.3 cm/s,
      p=0.001) and was unchanged in CONTROLS (20.1+/-4.2 vs. 20.9+/-5.1 cm/s, non
      significant). Despite similar asymmetric septal hypertrophy and normal global
      function during the first 2-4 weeks of pathologic and physiologic stress, there
      is an early reduction in systolic tissue velocity in pathologic but preserved in
      physiologic hypertrophy. Tissue velocities may help adjudicate between these 2
      states when there are no overt anatomic or functional differences.

PMID- 29357487
TI  - The effect of muscle-tendon unit vs. fascicle analyses on vastus lateralis force
      generating capacity during constant power output cycling with variable cadence.
AB  - The maximum force-generating capacity of a muscle is dependent on the lengths and
      velocities of its contractile apparatus. Muscle-tendon unit (MTU) length changes
      can be estimated from joint kinematics; however, contractile element length
      changes are more difficult to predict during dynamic contractions. The aim of
      this study was to compare vastus lateralis (VL) MTU and fascicle level force
      length and force-velocity relationships, and dynamic muscle function while
      cycling at a constant submaximal power output (2.5 W/kg) with different cadences.
      We hypothesized that manipulating cadence at a constant power output would not
      affect VL MTU shortening, but significantly affect VL fascicle shortening.
      Furthermore, these differences would affect the predicted force capacity of the
      muscle. Using an isokinetic dynamometer and B-mode ultrasound (US), we determined
      the force-length and force-velocity properties of the VL MTU and its fascicles.
      In addition, three-dimensional kinematics and kinetics of the lower limb, as well
      as US images of VL fascicles were collected during submaximal cycling at cadences
      of 40, 60, 80, and 100 rotations per minute. Ultrasound measures revealed a
      significant increase in fascicle shortening as cadence decreased (84% increase
      across all conditions, P < 0.01), whereas there were no significant differences
      in MTU lengths across any of the cycling conditions (maximum of 6%). The MTU
      analysis resulted in greater predicted force capacity across all conditions
      relative to the force-velocity relationship ( P < 0.01). These results reinforce
      the need to determine muscle mechanics in terms of separate contractile element
      and connective tissue length changes during isokinetic contractions, as well as
      dynamic movements like cycling. NEW & NOTEWORTHY We demonstrate that vastus
      lateralis (VL) muscle tendon unit (MTU) length changes do not adequately reflect
      the underlying fascicle mechanics during cycling. When examined across different
      pedaling cadence conditions, the force-generating potential measured only at the
      level of MTU (or joint) overestimated the maximum force capacity of VL compared
      with analysis using fascicle level data.

PMID- 29357488
TI  - Roller massage decreases spinal excitability to the soleus.
AB  - Roller massage (RM) interventions have shown acute increases in range of motion
      (ROM) and pain pressure threshold (PPT). It is unclear whether the RM-induced
      increases can be attributed to changes in neural or muscle responses. The purpose
      of this study was to evaluate the effect of altered afferent input via
      application of RM on spinal excitability, as measured with the Hoffmann (H-)
      reflex. A randomized within-subjects design was used. Three 30-s bouts of RM were
      implemented on a rested, nonexercised, injury-free muscle with 30 s of rest
      between bouts. The researcher applied RM to the plantar flexors at three
      intensities of pain: high, moderate, and sham. Measures included normalized M
      wave and H-reflex peak-to-peak amplitudes before, during, and up to 3 min
      postintervention. M-wave and H-reflex measures were highly reliable. RM resulted
      in significant decreases in soleus H-reflex amplitudes. High-intensity, moderate
      intensity, and sham conditions decreased soleus H-reflex amplitudes by 58%, 43%,
      and 19%, respectively. H-reflexes induced with high-intensity rolling discomfort
      or pain were significantly lower than moderate and sham conditions. The effects
      were transient in nature, with an immediate return to baseline following RM. This
      is the first evidence of RM-induced modulation of spinal excitability. The
      intensity-dependent response observed indicates that rolling pressure or pain
      perception may play a role in modulation of the inhibition. Roller massage
      induced neural modulation of spinal excitability may explain previously reported
      increases in ROM and PPT. NEW & NOTEWORTHY Recent evidence indicates that the
      benefits of foam rolling and roller massage are primarily accrued through neural
      mechanisms. The present study attempts to determine the neuromuscular response to
      roller massage interventions. We provide strong evidence of roller massage
      induced neural modulation of spinal excitability to the soleus. It is plausible
      that reflex inhibition may explain subsequent increases in pain pressure
      threshold.

PMID- 29357489
TI  - The partial pressure of carbon monoxide in human tissues calculated using a
      parallel capillary-tissue cylinder model.
AB  - Tissue PCO values have not been previously estimated under conditions where the
      blood carboxyhemoglobin % saturation ([COHb]) is at a normal level or increased.
      Tissue PCO values are not known for conditions when [COHb] is increased during CO
      therapy or during CO poisoning. Using a modified Krogh parallel capillary-tissue
      model, mean tissue PCO was calculated for when [COHb] was 1, 5, 10, and 15%
      saturation, relevant to CO therapy, and 20, 30, and 40% saturation, relevant to
      CO poisoning. Calculations were made for the time during which CO was being
      inhaled, after cessation of CO uptake, and for different O2 extractions from
      blood flowing in the model capillary. The T1/2 of relevant CO reactions was used
      in these calculations. When the [COHb] increased to 5 to 10% saturation, mean
      tissue PCO values increased to 500 to 1,100% of values when the [COHb] was 1%
      saturation. When the [COHb] increased to 20 to 40% saturation, mean tissue PCO
      values increased to 2,300 to 5,700% of the 1% saturation value. Results indicate
      the utility of the modified Krogh model in furthering understanding the
      physiology of determinants of tissue PCO and should facilitate future studies of
      in vivo CO binding to different extravascular heme proteins during CO therapy and
      during CO poisoning. NEW & NOTEWORTHY Tissue PCO levels resulting from
      carboxyhemoglobin concentrations achieved during CO therapy or during CO
      poisoning have not been previously estimated. Results published here show that at
      carboxyhemoglobin levels achieved during CO therapy there are 500 to 1,100%
      increases in mean tissue PCO values. With carboxyhemoglobin increases associated
      with toxic effects, there are 2,300 to 5,700% increases in the mean tissue PCO.
      These differences suggest a basis for understanding the therapeutic and toxic
      effects of CO.

PMID- 29357490
TI  - Chronic low-intensity exercise attenuates cardiomyocyte contractile dysfunction
      and impaired adrenergic responsiveness in aortic-banded mini-swine.
AB  - Exercise improves clinical outcomes in patients diagnosed with heart failure with
      reduced ejection fraction (HFrEF), in part via beneficial effects on
      cardiomyocyte Ca2+ cycling during excitation-contraction coupling (ECC). However,
      limited data exist regarding the effects of exercise training on cardiomyocyte
      function in patients diagnosed with heart failure with preserved ejection
      fraction (HFpEF). The purpose of this study was to investigate cardiomyocyte Ca2+
      handling and contractile function following chronic low-intensity exercise
      training in aortic-banded miniature swine and test the hypothesis that low
      intensity exercise improves cardiomyocyte function in a large animal model of
      pressure overload. Animals were divided into control (CON), aortic-banded
      sedentary (AB), and aortic-banded low-intensity trained (AB-LIT) groups. Left
      ventricular cardiomyocytes were electrically stimulated (0.5 Hz) to assess Ca2+
      homeostasis (fura-2-AM) and unloaded shortening during ECC under conditions of
      baseline pacing and pacing with adrenergic stimulation using dobutamine (1 MUM).
      Cardiomyocytes in AB animals exhibited depressed Ca2+ transient amplitude and
      cardiomyocyte shortening vs. CON under both conditions. Exercise training
      attenuated AB-induced decreases in cardiomyocyte Ca2+ transient amplitude but did
      not prevent impaired shortening vs. CON. With dobutamine, AB-LIT exhibited both
      Ca2+ transient and shortening amplitude similar to CON. Adrenergic sensitivity,
      assessed as the time to maximum inotropic response following dobutamine
      treatment, was depressed in the AB group but normal in AB-LIT animals. Taken
      together, our data suggest exercise training is beneficial for cardiomyocyte
      function via the effects on Ca2+ homeostasis and adrenergic sensitivity in a
      large animal model of pressure overload-induced heart failure. NEW & NOTEWORTHY
      Conventional treatments have failed to improve the prognosis of heart failure
      with preserved ejection fraction (HFpEF) patients. Our findings show chronic low
      intensity exercise training can prevent cardiomyocyte dysfunction and impaired
      adrenergic responsiveness in a translational large animal model of chronic
      pressure overload-induced heart failure with relevance to human HFpEF.

PMID- 29357491
TI  - Parathyroid hormone-(1-34) ameliorated knee osteoarthritis in rats via autophagy.
AB  - Anterior cruciate ligament (ACL) tear can lead to osteoarthritis (OA). However,
      parathyroid hormone (PTH)-(1-34) was found to alleviate OA progression in a
      papain-induced OA model. Autophagy is a protective mechanism in normal cartilage,
      and its aging-related loss is linked with chondrocyte death and OA. Thus we
      examined the roles of autophagy in PTH treatment in OA after ACL transection
      (ACLT). Thirty-six rats were randomized into three groups: control group, ACLT
      induced OA (OA) group, and OA with intra-articular PTH-(1-34) treatment (OA+PTH)
      group. Weight-bearing and treadmill tests were evaluated. Cartilage matrix was
      determined by a histological evaluation of glycosaminoglycan (GAG),
      Osteoarthritis Research Society International (OARSI) score, chondrocyte
      apoptosis, and immunohistochemistry. Rats in the OA group had significantly
      decreased weight bearing and running endurance. The histological results
      indicated that GAG, collagen type II, and chondrocyte autophagy had decreased but
      that the OARSI score, terminal differentiation markers (collagen type X and
      Indian hedgehog), and chondrocyte apoptosis had increased in the OA group.
      Additionally, PTH-(1-34) treatment significantly improved weight bearing and
      treadmill endurance, preserved GAG and collagen type II, and reduced the OARSI
      score and terminal differentiation markers. Finally, PTH-(1-34) ameliorated
      chondrocyte apoptosis by regulating the expression of autophagy-related proteins,
      through reducing mechanistic target of rapamycin (mTOR) and p62 and enhancing
      microtubule-associated protein-1 light chain 3 (LC3) and beclin-1. Reconstructive
      surgery after ACL rupture cannot prevent OA occurrence. Intra-articular PTH-(1
      34) treatment can alleviate OA progression after ACLT and histological molecular
      changes. Possible mechanisms are reducing chondrocyte terminal differentiation
      and apoptosis, with increasing autophagy. NEW & NOTEWORTHY Anterior cruciate
      ligament (ACL) tear can lead to osteoarthritis (OA). Intra-articular parathyroid
      hormone (PTH)-(1-34) significantly improved weight bearing and treadmill
      endurance, preserved glycosaminoglycan and collagen type II, and reduced
      Osteoarthritis Research Society International (OARSI) score and terminal
      differentiation. Finally, PTH-(1-34) ameliorated chondrocyte apoptosis by
      regulating the expression of autophagy-related proteins, through reducing
      mechanistic target of rapamycin (mTOR) and p62 and enhancing microtubule
      associated protein-1 light chain 3 (LC3) and beclin-1. PTH-(1-34) can alleviate
      OA progression after ACL transection. Possible mechanisms are reducing
      chondrocyte terminal differentiation and apoptosis, with increasing autophagy.

PMID- 29357492
TI  - Involvement of hypoglossal and recurrent laryngeal nerves on swallowing pressure.
AB  - Swallowing pressure generation is important to ensure safe transport of an
      ingested bolus without aspiration or leaving residue in the pharynx. To clarify
      the mechanism, we measured swallowing pressure at the oropharynx (OP), upper
      esophageal sphincter (UES), and cervical esophagus (CE) using a specially
      designed manometric catheter in anesthetized rats. A swallow, evoked by punctate
      mechanical stimulation to the larynx, was identified by recording activation of
      the suprahyoid and thyrohyoid muscles using electromyography (EMG). Areas under
      the curve of the swallowing pressure at the OP, UES, and CE from two trials
      indicated high intrasubject reproducibility. Effects of transecting the
      hypoglossal nerve (12N) and recurrent laryngeal nerve (RLN) on swallowing were
      investigated. Following bilateral hypoglossal nerve transection (Bi-12Nx), OP
      pressure was significantly decreased, and time intervals between peaks of
      thyrohyoid EMG bursts and OP pressure were significantly shorter. Decreased OP
      pressure and shortened times between peaks of thyrohyoid EMG bursts and OP
      pressure following Bi-12Nx were significantly increased and longer, respectively,
      after covering the hard and soft palates with acrylic material. UES pressure was
      significantly decreased after bilateral RLN transection compared with that before
      transection. These results suggest that the 12N and RLN play crucial roles in OP
      and UES pressure during swallowing, respectively. We speculate that covering the
      palates with a palatal augmentation prosthesis may reverse the reduced swallowing
      pressure in patients with 12N or tongue damage by the changes of the sensory
      information and of the contact between the tongue and a palates. NEW & NOTEWORTHY
      Hypoglossal nerve transection reduced swallowing pressure at the oropharynx.
      Covering the hard and soft palates with acrylic material may reverse the reduced
      swallowing function caused by hypoglossal nerve damage. Recurrent laryngeal nerve
      transection reduced upper esophageal sphincter negative pressure during
      swallowing.

PMID- 29357493
TI  - Diaphragm muscle activity across respiratory motor behaviors in awake and lightly
      anesthetized rats.
AB  - Respiratory muscles such as the diaphragm are active across a range of behaviors
      including ventilation and higher-force behaviors necessary for maintenance of
      airway patency, and minimal information is available regarding anesthetic effects
      on the capacity of respiratory muscles to generate higher forces. The purpose of
      the present study was to determine whether diaphragm EMG activity during lower
      force behaviors, such as eupnea and hypoxia-hypercapnia, is differentially
      affected compared with higher-force behaviors, such as a sigh, in lightly
      anesthetized animals. In adult male rats, chronically implanted diaphragm EMG
      electrodes were used to measure the effects of low-dose ketamine (30 mg/kg) and
      xylazine (3 mg/kg) on root mean square (RMS) EMG amplitude across a range of
      motor behaviors. A mixed linear model was used to evaluate the effects of
      ketamine-xylazine anesthesia on peak RMS EMG and ventilatory parameters, with
      condition (awake vs. anesthetized), behavior (eupnea, hypoxia-hypercapnia, sigh),
      side (left or right hemidiaphragm), and their interactions as fixed effects and
      animal as a random effect. Compared with the awake recordings, there was an
      overall reduction of peak diaphragm RMS EMG across behaviors during anesthesia,
      but this reduction was more pronounced during spontaneous sighs (which require
      ~60% of maximal diaphragm force). Respiratory rates and duty cycle during eupnea
      and hypoxia-hypercapnia were higher in awake compared with anesthetized
      conditions. These results highlight the importance of identifying anesthetic
      effects on a range of respiratory motor behaviors, including sighs necessary for
      maintaining airway patency. NEW & NOTEWORTHY Respiratory muscles accomplish a
      range of motor behaviors, with forces generated for ventilatory behaviors
      comprising only a small fraction of their maximal force generating capacity.
      Induction of anesthesia exerts more robust effects on the higher-force diaphragm
      motor behaviors such as sighs compared with eupnea. This novel information on
      effects of low, sedative doses of a commonly used anesthetic combination
      (ketamine-xylazine) highlights the importance of identifying anesthetic effects
      on a range of respiratory motor behaviors.

PMID- 29357494
TI  - Beetroot juice ingestion during prolonged moderate-intensity exercise attenuates
      progressive rise in O2 uptake.
AB  - Nitrate-rich beetroot juice (BR) supplementation has been shown to increase
      biomarkers of nitric oxide availability with implications for the physiological
      responses to exercise. We hypothesized that BR supplementation before and during
      prolonged moderate-intensity exercise would maintain an elevated plasma nitrite
      concentration ([[Formula: see text]]), attenuate the expected progressive
      increase in Vo2 over time, and improve performance in a subsequent time trial
      (TT). In a double-blind, randomized, crossover design, 12 men completed 2 h of
      moderate-intensity cycle exercise followed by a 100-kJ TT in three conditions: 1)
      BR before and 1 h into exercise (BR + BR); 2) BR before and placebo (PL) 1 h into
      exercise (BR + PL); and 3) PL before and 1 h into exercise (PL + PL). During the
      2-h moderate-intensity exercise bout, plasma [[Formula: see text]] declined by
      ~17% in BR + PL but increased by ~8% in BR + BR such that, at 2 h, plasma
      [[Formula: see text]] was greater in BR + BR than both BR + PL and PL + PL ( P <
      0.05). Vo2 was not different among conditions over the first 90 min of exercise
      but was lower at 120 min in BR + BR (1.73 +/- 0.24 l/min) compared with BR + PL
      (1.80 +/- 0.21 l/min; P = 0.08) and PL + PL (1.83 +/- 0.27 l/min; P < 0.01). The
      decline in muscle glycogen concentration over the 2-h exercise bout was
      attenuated in BR + BR (~28% decline) compared with BR + PL (~44% decline) and PL
      + PL (~44% decline; n = 9, P < 0.05). TT performance was not different among
      conditions ( P > 0.05). BR supplementation before and during prolonged moderate
      intensity exercise attenuated the progressive rise in Vo2 over time and appeared
      to reduce muscle glycogen depletion but did not enhance subsequent TT
      performance. NEW & NOTEWORTHY We show for the first time that ingestion of
      nitrate during exercise preserves elevated plasma [nitrite] and negates the
      progressive rise in O2 uptake during prolonged moderate-intensity exercise.

PMID- 29357495
TI  - Force-velocity test on a stationary cycle ergometer: methodological
      recommendations.
AB  - Force-velocity tests performed on stationary cycle ergometers are widely used to
      assess the torque- and power-generating capacities of the lower limbs. The aim of
      this study was to identify how testing and modeling procedures influence the
      assessment of individual torque-cadence and power-cadence relationships.
      Seventeen males completed 62 +/- 16 pedal cycles from six 6-s all-out efforts
      interspersed with 5 min of rest. True measures of maximal power for a particular
      cadence were obtained for 24 +/- 3 pedal cycles, while power was only 94 +/- 3%
      of the true maximum in 19 +/- 5 pedal cycles. Pedal cycles showing maximal levels
      of power also displayed higher levels of electromyography (EMG: 89 +/- 7 vs . 87
      +/- 7%) and coactivation (34 +/- 11 vs . 31 +/- 10 arbitrary units), as well as
      lower variability in crank torque and EMG profiles. Compared with the linear and
      second-order polynomial models that are traditionally used, a better goodness of
      fit was obtained when the torque-cadence and power-cadence relationships were
      predicted using second- and third-order polynomials, respectively. The later
      modeling procedures also revealed an asymmetry in the power-cadence relationship
      in most participants (i.e., 15 out of 17) and provided a better estimation of
      maximal cadence [Cmax: 214 +/- 20 revolutions/min (rpm)] from the x-intercept of
      power-cadence relationships (C0: 214 +/- 14 rpm). Therefore, we recommend
      predicting the individual shapes of torque- and power-cadence relationships using
      second- and third-order polynomial regressions after having selected pedal cycles
      during which true measures of cadence-specific maximal power were recorded. NEW &
      NOTEWORTHY This study is the first to demonstrate that suboptimal activation of
      the lower limb muscles accompanied reductions in cadence-specific levels of
      torque and power produced during a force-velocity test performed on a stationary
      cycle ergometer. This research is also the first to show that, in most noncyclist
      participants, torque-cadence relationships are not linear, whereas power-cadence
      relationships display asymmetric shapes, with power production decreasing rapidly
      when cadence increases beyond 180 revolutions/min.

PMID- 29357496
TI  - Altered skeletal muscle mitochondrial phenotype in COPD: disease vs. disuse.
AB  - Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered
      skeletal muscle mitochondrial phenotype, which often includes reduced
      mitochondrial density, altered respiratory function, and elevated oxidative
      stress. As this phenotype may be explained by the sedentary lifestyle that
      commonly accompanies this disease, the aim of this study was to determine whether
      such alterations are still evident when patients with COPD are compared to
      control subjects matched for objectively measured physical activity (PA;
      accelerometry). Indexes of mitochondrial density [citrate synthase (CS)
      activity], respiratory function (respirometry in permeabilized fibers), and
      muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in
      muscle fibers biopsied from the vastus lateralis of nine patients with COPD and
      nine PA-matched control subjects (CON). Despite performing similar levels of PA
      (CON: 18 +/- 3, COPD: 20 +/- 7 daily minutes moderate-to-vigorous PA; CON: 4,596
      +/- 683, COPD: 4,219 +/- 763 steps per day, P > 0.70), patients with COPD still
      exhibited several alterations in their mitochondrial phenotype, including
      attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 +/- 3.8,
      COPD 52.7 +/- 6.5 U/mg, P < 0.05), altered mitochondrial respiration [e.g., ratio
      of complex I-driven state 3 to complex II-driven state 3 (CI/CII); CON: 1.20 +/-
      0.11, COPD: 0.90 +/- 0.05, P < 0.05), and oxidative stress (4-HNE; CON: 1.35 +/-
      0.19, COPD: 2.26 +/- 0.25 relative to beta-actin, P < 0.05). Furthermore, CS
      activity ( r = 0.55), CI/CII ( r = 0.60), and 4-HNE ( r = 0.49) were all
      correlated with pulmonary function, assessed as forced expiratory volume in 1 s (
      P < 0.05), but not PA ( P > 0.05). In conclusion, the altered mitochondrial
      phenotype in COPD is present even in the absence of differing levels of PA and
      appears to be related to the disease itself. NEW & NOTEWORTHY Chronic obstructive
      pulmonary disease (COPD) is associated with debilitating alterations in the
      function of skeletal muscle mitochondria. By comparing the mitochondrial
      phenotype of patients with COPD to that of healthy control subjects who perform
      the same amount of physical activity each day, this study provides evidence that
      many aspects of the dysfunctional mitochondrial phenotype observed in COPD are
      not merely due to reduced physical activity but are likely related to the disease
      itself.

PMID- 29357498
TI  - Validity and reliability of a novel metabolic flexibility test in children with
      obesity.
AB  - Existing methods for diagnosing diabetes and for identifying risk of diabetes
      development are completed under resting conditions and based on adult data.
      Studying additional methods to identify metabolic risk in children is warranted.
      Our objective was to examine the validity and reliability of a metabolic
      flexibility (MetFlex) test for screening glycemia and insulin resistance (IR) in
      children. We hypothesized higher MetFlex during exercise would be correlated with
      lower fasting glucose and homeostasis model assessment of insulin resistance
      (HOMA-IR) and higher whole body insulin sensitivity index (WBISI) and insulin
      secretion-sensitivity index-2 (ISSI-2). Thirty-four children with obesity (14
      boys, 20 girls) attended two visits. At visit 1, an oral glucose tolerance test
      (OGTT) was followed by anthropometric and aerobic fitness (Vo2max) assessments.
      Insulin and glucose during the OGTT were used to calculate HOMA-IR, WBISI, and
      ISSI-2. At visit 2, a 13C-enriched carbohydrate drink was ingested before 60 min
      of exercise at 45% Vo2max. Breath measurements were collected to calculate area
      under the curve exogenous carbohydrate to measure MetFlex. Pearson's r
      correlation showed no significant association between MetFlex during exercise
      with fasting glucose ( r = -0.288, P = 0.110). MetFlex was associated with log
      HOMA-IR ( r = -0.597, P = 0.024), log-WBISI ( r = 0.575, P = 0.051), and log-ISSI
      2 ( r = 0.605, P = 0.037) in boys but not girls. When repeated ( n = 18), MetFlex
      was deemed a reliable test (intraclass correlation coefficient = 0.692). MetFlex
      during exercise was negatively associated with IR and beta-cell function in boys.
      Further research is required to explore clinical utility of the MetFlex test and
      explain the lack of association in girls. NEW & NOTEWORTHY This study is the
      first to investigate the validity and reliability of a novel noninvasive
      metabolic flexibility (MetFlex) test for identifying insulin resistance in
      children with obesity. MetFlex was measured during exercise using [13C]glucose
      stable isotope methodology. Findings showed that MetFlex was negatively
      associated with insulin resistance in boys but not in girls with obesity. Future
      work is required to investigate these sex differences. MetFlex test results were
      deemed reliable when repeated on a separate day.

PMID- 29357497
TI  - Temporal characteristics of exercise-induced diaphragmatic fatigue.
AB  - There is evidence suggesting diaphragmatic fatigue (DF) occurs relatively early
      during high-intensity exercise; however, studies investigating the temporal
      characteristics of exercise-induced DF are limited by incongruent methodology.
      Eight healthy adult males (25 +/- 5 yr) performed a maximal incremental exercise
      test on a cycle ergometer on day 1. A constant-load time-to-exhaustion (TTE)
      exercise test was conducted on day 2 at 60% delta between the calculated gas
      exchange threshold and peak work rate. Two additional constant-load exercise
      tests were performed at the same intensity on days 3 and 4 in a random order to
      either 50 or 75% TTE. DF was assessed on days 2, 3, and 4 by measuring
      transdiaphragmatic twitch pressure (Pdi,tw) in response to cervical magnetic
      stimulation. DF was present after 75 and 100% TTE (>=20% decrease in Pdi,tw). The
      magnitude of fatigue was 15.5 +/- 5.7%, 23.6 +/- 6.4%, and 35.0 +/- 12.1% at 50,
      75, and 100% TTE, respectively. Significant differences were found between 100 to
      75 and 50% TTE (both P < 0.01), and 75 to 50% TTE ( P < 0.01). There was a
      significant relationship between the magnitude of fatigue and cumulative
      diaphragm force output ( r = 0.785; P < 0.001). Ventilation, the mechanical work
      of breathing (WOB), and pressure-time products were not different between trials
      ( P > 0.05). Our data indicate that exercise-induced DF presents a relatively
      late onset and is proportional to the cumulative WOB; thus the ability of the
      diaphragm to generate pressure progressively declines throughout exercise. NEW &
      NOTEWORTHY The notion that diaphragmatic fatigue (DF) occurs relatively early
      during exercise is equivocal. Our results indicate that DF occurs during high
      intensity endurance exercise in healthy men and its magnitude is strongly related
      to the amount of pressure and work generated by respiratory muscles. Thus we
      conclude that the work of breathing is the major determinant of exercise-induced
      DF.

PMID- 29357499
TI  - Effects of hypothermia and rewarming on cardiovascular autonomic control in vivo.
AB  - Rewarming from accidental hypothermia is associated with cardiovascular
      dysfunction that complicates rewarming and contributes to a high mortality rate.
      We investigated autonomic cardiovascular control, as well as the separate effects
      of cooling, hypothermia, and rewarming on hemodynamic function, aiming to provide
      knowledge of the pathophysiology causing such complications in these patients. A
      rat model designed for circulatory studies during cooling, hypothermia (15
      degrees C), and rewarming was used. Spectral analysis of diastolic arterial
      pressure and heart rate allowed assessment of the autonomic nervous system.
      Hemodynamic variables were monitored using a conductance catheter in the left
      ventricle and a pressure transducer connected to the left femoral artery.
      Sympathetic cardiovascular control was reduced after rewarming. Stroke volume
      increased during cooling but decreased during stable hypothermia and did not
      normalize during rewarming. Despite autonomic dysfunction, total peripheral
      resistance increased during cooling and did not normalize after rewarming. The
      present data show that sympathetic cardiovascular control is reduced by
      hypothermia and rewarming. A simultaneous systolic dysfunction is seen in
      rewarmed animals, caused by reduced filling of the left ventricle and impaired
      contractile function, in the presence of normal diastolic function. These
      findings show that dysfunction of the efferent sympathetic nervous system could
      be instrumental in development of rewarming shock. NEW & NOTEWORTHY The present
      study shows impaired autonomic control of cardiovascular function after rewarming
      from severe hypothermia. In victims of accidental hypothermia, rewarming shock is
      a much feared and lethal complication. The pathophysiology causing such
      cardiovascular collapse appears complex. Our findings indicate that dysfunction
      of the autonomic nervous system is an important part of the pathophysiology. Thus
      the present study gives novel information, important for further development of
      treatment strategies in this patient group.

PMID- 29357500
TI  - Cardiorespiratory and muscle oxygenation responses to low-load/high-repetition
      resistance exercises in COPD and healthy controls.
AB  - Single-limb exercises have been used as a strategy to improve aerobic exercise
      tolerance in patients with chronic obstructive pulmonary disease (COPD) by
      alleviating the cardiopulmonary demand. We asked whether this strategy would also
      apply to cardiorespiratory demand and amount of work performed during single-limb
      and two-limb low-load/high-repetition resistance exercises in 20 patients with
      COPD [forced expiratory volume in 1 s (FEV1) = 1.0 liters, 38% of predicted] and
      15 age-, sex-, and activity-matched healthy controls. Peak ventilation, peak
      oxygen consumption (Vo2), and peak heart rate (HR) were assessed to document
      cardiorespiratory demand during shoulder flexion and knee extension exercises
      while exercise tolerance was assessed by the total amount of work achieved. In
      addition, changes in myoglobin-deoxyhemoglobin level (Deltadeoxy-[Hb/Mb]) were
      measured during single-limb knee extension. In COPD, single-limb shoulder flexion
      and knee extension elicited higher localized workloads than two-limb exercises
      (21 and 24% higher workloads for the former exercise) while cardiopulmonary
      demand was 8-16% higher during two-limb exercises. When expressed as a percentage
      of peak values achieved during incremental cycle ergometry, peak VO2 and HR were
      similarly high during single-limb shoulder flexion and knee extension exercises,
      representing 90% of peak HR and 60% of peak VO2. Apart from single-limb knee
      extension, cardiorespiratory demand per kilogram work during low-load/high
      repetition knee extension and shoulder flexion exercises was higher in patients
      with COPD than in healthy controls (range 27-122%, P < 0.0125). Deltadeoxy
      [Hb/Mb] of the quadriceps during knee extension was similar between the two
      groups, while Deltadeoxy-[Hb/Mb] per kilogram work was higher in patients with
      COPD. We conclude that 1) in patients with COPD, single-limb exercises resulted
      in lower peak cardiorespiratory demand as well as higher localized workloads
      compared with two-limb exercises; 2) compared with healthy controls, the
      cardiorespiratory demand, either expressed per unit of work or relative to peak
      capacity, was higher in patients with COPD than in controls during low-load/high
      repetition resistance exercises, irrespective of the involvement of one or two
      limbs or of the upper or lower extremity; 3) quadriceps muscle deoxygenation per
      unit of work during low-load/high-repetition knee extension was increased in COPD
      compared with controls; and 4) single- and two-limb low-load/high-repetition knee
      extension and shoulder flexion resistance exercises imposed a similar burden on
      the cardiorespiratory system, resulting in a higher cardiorespiratory demand per
      kilogram work performed during shoulder flexion compared with knee extension, in
      both COPD and healthy controls. NEW & NOTEWORTHY In chronic obstructive pulmonary
      disease (COPD), single-limb knee extension and shoulder flexion resulted in a
      lower peak cardiorespiratory response as well as larger localized exercise
      workloads compared with two-limb exercises. Cardiorespiratory and quadriceps
      deoxygenation cost per kilogram work was greater in COPD compared with healthy
      controls, despite similar acute responses. Compared with knee extension, shoulder
      flexion imposed a similar burden on the cardiorespiratory system in patients with
      COPD and healthy controls.

PMID- 29357501
TI  - Effects of aging and Parkinson's disease on motor unit remodeling: influence of
      resistance exercise training.
AB  - Aging muscle atrophy is in part a neurodegenerative process revealed by
      denervation/reinnervation events leading to motor unit remodeling (i.e., myofiber
      type grouping). However, this process and its physiological relevance are poorly
      understood, as is the wide-ranging heterogeneity among aging humans. Here, we
      attempted to address 1) the relation between myofiber type grouping and molecular
      regulators of neuromuscular junction (NMJ) stability; 2) the impact of motor unit
      remodeling on recruitment during submaximal contractions; 3) the prevalence and
      impact of motor unit remodeling in Parkinson's disease (PD), an age-related
      neurodegenerative disease; and 4) the influence of resistance exercise training
      (RT) on regulators of motor unit remodeling. We compared type I myofiber
      grouping, molecular regulators of NMJ stability, and the relative motor unit
      activation (MUA) requirement during a submaximal sit-to-stand task among
      untrained but otherwise healthy young (YA; 26 yr, n = 27) and older (OA; 66 yr, n
      = 91) adults and OA with PD (PD; 67 yr, n = 19). We tested the effects of RT on
      these outcomes in OA and PD. PD displayed more motor unit remodeling, alterations
      in NMJ stability regulation, and a higher relative MUA requirement than OA,
      suggesting PD-specific effects. The molecular and physiological outcomes tracked
      with the severity of type I myofiber grouping. Together these findings suggest
      that age-related motor unit remodeling, manifested by type I myofiber grouping,
      1) reduces MUA efficiency to meet submaximal contraction demand, 2) is associated
      with disruptions in NMJ stability, 3) is further impacted by PD, and 4) may be
      improved by RT in severe cases. NEW & NOTEWORTHY Because the physiological
      consequences of varying amounts of myofiber type grouping are unknown, the
      current study aims to characterize the molecular and physiological correlates of
      motor unit remodeling. Furthermore, because exercise training has demonstrated
      neuromuscular benefits in aged humans and improved innervation status and
      neuromuscular junction integrity in animals, we provide an exploratory analysis
      of the effects of high-intensity resistance training on markers of neuromuscular
      degeneration in both Parkinson's disease (PD) and age-matched older adults.

PMID- 29357502
TI  - Mitochondrial dysfunction in iPSC-derived neurons of subjects with chronic
      mountain sickness.
AB  - Patients with chronic mountain sickness (CMS) suffer from hypoxemia,
      erythrocytosis, and numerous neurologic deficits. Here we used induced
      pluripotent stem cell (iPSC)-derived neurons from both CMS and non-CMS subjects
      to study CMS neuropathology. Using transmission electron microscopy, we report
      that CMS neurons have a decreased mitochondrial volume density, length, and less
      cristae membrane surface area. Real-time PCR confirmed a decreased mitochondrial
      fusion gene optic atrophy 1 (OPA1) expression. Immunoblot analysis showed an
      accumulation of the short isoform of OPA1 (S-OPA1) in CMS neurons, which have
      reduced ATP levels under normoxia and increased lactate dehydrogenase (LDH)
      release and caspase 3 activation after hypoxia. Improving the balance between the
      long isoform of OPA1 and S-OPA1 in CMS neurons increased the ATP levels and
      attenuated LDH release under hypoxia. Our data provide initial evidence for
      altered mitochondrial morphology and function in CMS neurons, and reveal
      increased cell death under hypoxia due in part to altered mitochondrial dynamics.
      NEW & NOTEWORTHY Induced pluripotent stem cell-derived neurons from chronic
      mountain sickness (CMS) subjects have altered mitochondrial morphology and
      dynamics, and increased sensitivity to hypoxic stress. Modification of OPA1 can
      attenuate cell death after hypoxic treatment, providing evidence that altered
      mitochondrial dynamics play an important role in increased vulnerability under
      stress in CMS neurons.

PMID- 29357503
TI  - Hypothalamic PVN contributes to acute intermittent hypoxia-induced sympathetic
      but not phrenic long-term facilitation.
AB  - Blackburn MB, Andrade MA, Toney GM. Hypothalamic PVN contributes to acute
      intermittent hypoxia-induced sympathetic but not phrenic long-term facilitation.
      J Appl Physiol 124: 1233-1243, 2018. First published December 19, 2017; doi:
      10.1152/japplphysiol.00743.2017 .- Acute intermittent hypoxia (AIH) repetitively
      activates the arterial chemoreflex and triggers a progressive increase of
      sympathetic nerve activity (SNA) and phrenic nerve activity (PNA) referred to as
      sympathetic and phrenic long-term facilitation (S-LTF and P-LTF), respectively.
      Neurons of the hypothalamic paraventricular nucleus (PVN) participate in the
      arterial chemoreflex, but their contribution to AIH-induced LTF is unknown. To
      determine this, anesthetized rats were vagotomized and exposed to 10 cycles of
      AIH, each consisting of ventilation for 3 min with 100% O2 followed by 3 min with
      15% O2. Before AIH, rats received bilateral PVN injections of artificial
      cerebrospinal fluid (aCSF; vehicle) or the GABA-A receptor agonist muscimol (100
      pmol in 50 nl) to inhibit neuronal activity. Thirty minutes after completing the
      AIH protocol, during which rats were continuously ventilated with 100% O2, S-LTF
      and P-LTF were quantified from recordings of integrated splanchnic SNA and PNA,
      respectively. PVN muscimol attenuated increases of SNA during hypoxic episodes
      occurring in later cycles (6-10) of AIH ( P < 0.03) and attenuated post-AIH S-LTF
      ( P < 0.001). Muscimol, however, did not consistently affect peak PNA responses
      during hypoxic episodes and did not alter AIH-induced P-LTF. These findings
      indicate that PVN neuronal activity contributes to sympathetic responses during
      AIH and to subsequent generation of S-LTF. NEW & NOTEWORTHY Neural circuits
      mediating acute intermittent hypoxia (AIH)-induced sympathetic and phrenic long
      term facilitation (LTF) have not been fully elucidated. We found that
      paraventricular nucleus (PVN) inhibition attenuated sympathetic activation during
      episodes of AIH and reduced post-AIH sympathetic LTF. Neither phrenic burst
      patterning nor the magnitude of AIH-induced phrenic LTF was affected. Findings
      indicate that PVN neurons contribute to AIH-induced sympathetic LTF. Defining
      mechanisms of sympathetic LTF could improve strategies to reduce sympathetic
      activity in cardiovascular and metabolic diseases.

PMID- 29357504
TI  - Short-term menthol treatment promotes persistent thermogenesis without induction
      of compensatory food consumption in Wistar rats: implications for obesity
      control.
AB  - In this study, we aimed to evaluate the influence of daily repeated menthol
      treatments on body mass and thermoregulatory effectors in Wistar rats,
      considering that menthol is a transient receptor potential melastatin 8 channel
      agonist that mimics cold sensation and activates thermoregulatory cold-defense
      mechanisms in mammals, promoting hyperthermia and increasing energy expenditure,
      and has been suggested as an anti-obesity drug. Male Wistar rats were topically
      treated with 5% menthol for 3 or 9 consecutive days while body mass, food intake,
      abdominal temperature, metabolism, cutaneous vasoconstriction, and thermal
      preference were measured. Menthol promoted hyperthermia on all days of treatment,
      due to an increase in metabolism and cutaneous vasoconstriction, without
      affecting food intake, resulting in less mass gain in menthol-hyperthermic
      animals. As the treatment progressed, the menthol-induced increases in metabolism
      and hyperthermia were attenuated but not abolished. Moreover, cutaneous
      vasoconstriction was potentiated, and an increase in the warmth-seeking behavior
      was induced. Taken together, the results suggest that, although changes occur in
      thermoeffector recruitment during the course of short-term treatment, menthol is
      a promising drug to prevent body mass gain. NEW & NOTEWORTHY Menthol produces a
      persistent increase in energy expenditure, with limited compensatory
      thermoregulatory adaptations and, most unexpectedly, without affecting food
      intake. Thus short-term treatment with menthol results in less mass gain in
      treated animals compared with controls. Our results suggest that menthol is a
      promising drug for the prevention of obesity.

PMID- 29357505
TI  - Chemoreflex mediated arrhythmia during apnea at 5,050 m in low- but not high
      altitude natives.
AB  - Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic
      drive under chronic hypoxia may evoke bradyarrhythmias during apneic periods. We
      determined whether 1) voluntary apnea unmasks arrhythmia at low (344 m) and high
      (5,050 m) altitude, 2) high-altitude natives (Nepalese Sherpa) exhibit similar
      cardiovagal responses at altitude, and 3) bradyarrhythmias at altitude are
      partially chemoreflex mediated. Participants were grouped as Lowlanders ( n = 14;
      age = 27 +/- 6 yr) and Nepalese Sherpa ( n = 8; age = 32 +/- 11 yr). Lowlanders
      were assessed at 344 and 5,050 m, whereas Sherpa were assessed at 5,050 m. Heart
      rate (HR) and rhythm (lead II ECG) were recorded during rest and voluntary end
      expiratory apnea. Peripheral chemoreflex contributions were assessed in
      Lowlanders ( n = 7) at altitude after 100% oxygen. Lowlanders had higher resting
      HR at altitude (70 +/- 15 vs. 61 +/- 15 beats/min; P < 0.01) that was similar to
      Sherpa (71 +/- 5 beats/min; P = 0.94). High-altitude apnea caused arrhythmias in
      11 of 14 Lowlanders [junctional rhythm ( n = 4), 3 degrees  atrioventricular
      block ( n = 3), sinus pause ( n = 4)] not present at low altitude and larger
      marked bradycardia (nadir -39 +/- 18 beats/min; P < 0.001). Sherpa exhibited a
      reduced bradycardia response during apnea compared with Lowlanders ( P < 0.001)
      and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir -10 +/- 14
      beats/min; P < 0.001 compared with hypoxic state) and reduced arrhythmia
      incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to
      hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias ( P
      < 0.05). Our data demonstrate apnea-induced bradyarrhythmias in Lowlanders at
      altitude but not in Sherpa (potentially through cardioprotective phenotypes). The
      chemoreflex is an important mechanism in genesis of bradyarrhythmias, and the HVR
      may be predictive for identifying individual susceptibility to events at
      altitude. NEW & NOTEWORTHY The peripheral chemoreflex increases both
      parasympathetic and sympathetic drive under chronic hypoxia. We found that this
      evoked bradyarrhythmias when combined with apneic periods in Lowlanders at
      altitude, which become relieved through supplemental oxygen. In contrast, high
      altitude residents (Nepalese Sherpa) do not exhibit bradyarrhythmias during apnea
      at altitude through potential cardioprotective adaptations. The degree of
      bradycardia and bradyarrhythmias was related to the hypoxic ventilatory response,
      demonstrating that the chemoreflex plays an important role in these findings.

PMID- 29357506
TI  - A model-based approach to interpreting multibreath nitrogen washout data.
AB  - The multibreath nitrogen washout (MBNW) test, as it is currently practiced,
      provides parameters of potential physiological significance that are derived from
      the relationship between the volume-normalized Phase III slope of the exhaled
      nitrogen fraction ([Formula: see text]) vs. the cumulative change in lung volume
      (V). Reliable evaluation of these parameters requires, however, that the subject
      breathe deeply and evenly, so that Phase III can be clearly identified in every
      breath. This places a burden on the test subject that may prove troublesome for
      young children and those with lung disease. Furthermore, the determination of the
      slope of Phase III requires that a decision be made as to when Phase II ends and
      Phase III begins. In an attempt to get around these methodological limitations,
      we develop here an alternative method of analysis based on a multicompartment
      model of the lung that accounts for the entire exhaled nitrogen profile,
      including Phases I, II, and III. Fitting this model to [Formula: see text] and V
      measured during a MBNW provides an estimate of the coefficient of variation of
      specific ventilation, as well as functional residual capacity, dead space volume,
      and a parameter that reflects structural asymmetry at the acinar level in the
      lung. In the present study, we demonstrate the potential utility of this modeling
      approach to the analysis of MBNW data. NEW & NOTEWORTHY The multibreath nitrogen
      washout test potentially provides important physiological information about
      regional ventilation heterogeneity throughout the lung, but the conventional
      analysis requires the subject to breathe deeply and regularly, which is not
      always practical. We have developed a model-based analysis method that avoids
      this limitation and that also provides measures of functional residual capacity
      and dead space volume, thereby expanding the applicability and scope of the
      method.

PMID- 29357507
TI  - Reinventing the wheel: comparison of two wheel cage styles for assessing mouse
      voluntary running activity.
AB  - Voluntary wheel cage assessment of mouse activity is commonly employed in
      exercise and behavioral research. Currently, no standardization for wheel cages
      exists resulting in an inability to compare results among data from different
      laboratories. The purpose of this study was to determine whether the distance run
      or average speed data differ depending on the use of two commonly used
      commercially available wheel cage systems. Two different wheel cages with
      structurally similar but functionally different wheels (electromechanical switch
      vs. magnetic switch) were compared side-by-side to measure wheel running data
      differences. Other variables, including enrichment and cage location, were also
      tested to assess potential impacts on the running wheel data. We found that cages
      with the electromechanical switch had greater inherent wheel resistance and
      consistently led to greater running distance per day and higher average running
      speed. Mice rapidly, within 1-2 days, adapted their running behavior to the type
      of experimental switch used, suggesting these running differences are more
      behavioral than due to intrinsic musculoskeletal, cardiovascular, or metabolic
      limits. The presence of enrichment or location of the cage had no detectable
      impact on voluntary wheel running. These results demonstrate that mice run
      differing amounts depending on the type of cage and switch mechanism used and
      thus investigators need to report wheel cage type/wheel resistance and use
      caution when interpreting distance/speed run across studies. NEW & NOTEWORTHY The
      results of this study highlight that mice will run different distances per day
      and average speed based on the inherent resistance present in the switch
      mechanism used to record data. Rapid changes in running behavior for the same
      mouse in the different cages demonstrate that a strong behavioral factor
      contributes to classic exercise outcomes in mice. Caution needs to be taken when
      interpreting mouse voluntary wheel running activity to include potential
      behavioral input and physiological parameters.

PMID- 29357508
TI  - Early blood pressure response to isometric exercise is attenuated in obese
      individuals who have undergone bariatric surgery.
AB  - Blood pressure (BP) reactivity is predictive of the development of cardiovascular
      disease. We hypothesized that the BP response at the onset of isometric handgrip
      exercise would occur earlier and to a lesser degree in individuals who underwent
      bariatric surgery compared with obese adults and that the reliance on total
      peripheral resistance (TPR) would be attenuated. Twenty-six individuals (7
      nonobese, 11 obese, 8 postbariatric surgery) completed isometric handgrip
      exercise (40% maximum voluntary contraction) to exhaustion. Heart rate (HR, ECG)
      and arterial BP (brachial catheter) were measured continuously. Stroke volume was
      estimated from the pressure waveform, and cardiac output (CO) and TPR were
      calculated. Peak change, time to peak, and rate of rise in BP were assessed
      during the first 30 s of exercise. Obese adults exhibited a slower rise in BP and
      higher peak BP at exercise onset compared with nonobese controls ( P < 0.05).
      Peak BP and the rate of rise were not different between individuals who underwent
      bariatric surgery and nonobese controls ( P > 0.05). Nonobese controls exhibited
      an exercise-mediated increase in CO, whereas obese adults increased TPR ( P <
      0.05). The increases in CO and TPR were less apparent in individuals who
      underwent bariatric surgery ( P > 0.05). In contrast to obese adults, individuals
      who underwent bariatric surgery exhibit a rapid rise in BP at exercise onset.
      This rapid increase in BP is associated with a fall in TPR and results in lower
      peak BP at the onset of isometric exercise. These data suggest that bariatric
      surgery improves BP reactivity via changes in the time course of hemodynamic
      responses. NEW & NOTEWORTHY Bariatric surgery has been shown to reduce the blood
      pressure (BP) response to isometric handgrip exercise. By examining the time
      course of the BP response to exercise, we found, in contrast to obese adults,
      individuals who underwent bariatric surgery exhibit a rapid rise in BP at
      exercise onset, which is associated with a fall in total peripheral resistance
      and results in lower peak BP at the onset of isometric exercise. These data
      suggest that bariatric surgery improves BP reactivity via reflex autonomic
      adjustments.

PMID- 29357509
TI  - Benzolamide perpetuates acidic conditions during reperfusion and reduces
      myocardial ischemia-reperfusion injury.
AB  - During ischemia, increased anaerobic glycolysis results in intracellular
      acidosis. Activation of alkalinizing transport mechanisms associated with
      carbonic anhydrases (CAs) leads to myocardial intracellular Ca2+ increase. We
      characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac
      ischemia-reperfusion (I/R). Langendorff-perfused isolated rat hearts were
      subjected to 30 min of global ischemia and 60 min of reperfusion. Other hearts
      were treated with BZ (5 MUM) during the initial 10 min of reperfusion or perfused
      with acid solution (AR, pH 6.4) during the first 3 min of reperfusion. p38MAPK, a
      kinase linked to membrane transporters and involved in cardioprotection, was
      examined in hearts treated with BZ in presence of the p38MAPK inhibitor SB202190
      (10 MUM). Infarct size (IZ) and myocardial function were assessed, and
      phosphorylated forms of p38MAPK, Akt, and PKCepsilon were evaluated by
      immunoblotting. We determined the rate of intracellular pH (pHi) normalization
      after transient acid loading in the absence and presence of BZ or BZ + SB202190
      in heart papillary muscles (HPMs). Mitochondrial membrane potential (DeltaPsim),
      Ca2+ retention capacity and Ca2+-mediated swelling after I/R were also measured.
      BZ, similarly to AR, reduced IZ, improved postischemic recovery of myocardial
      contractility, increased phosphorylation of Akt, PKCepsilon, and p38MAPK, and
      normalized DeltaPsim and Ca2+ homeostasis, effects abolished after p38MAPK
      inhibition. In HPMs, BZ slowed pHi recovery, an effect that was restored after
      p38MAPK inhibition. We conclude that prolongation of acidic conditions during
      reperfusion by BZ could be responsible for the cardioprotective benefits of
      reduced infarction and better myocontractile function, through p38MAPK-dependent
      pathways. NEW & NOTEWORTHY Carbonic anhydrase inhibition by benzolamide (BZ)
      maintains acidity, decreases infarct size, and improves postischemic myocardial
      dysfunction in ischemia-reperfusion (I/R) hearts. Protection afforded by BZ
      mimicked the beneficial effects elicited by an acidic solution (AR). Increased
      phosphorylation of p38MAPK occurs in I/R hearts reperfused with BZ or with AR.
      Mitochondria from I/R hearts possess abnormal Ca2+ handling and a more
      depolarized membrane potential compared with control hearts, and these changes
      were restored by treatment with BZ or AR.

PMID- 29357510
TI  - GBT1118, a compound that increases the oxygen affinity of hemoglobin, improves
      survival in murine hypoxic acute lung injury.
AB  - Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation
      and pulmonary edema, leading to arterial hypoxemia and death if the hypoxemia is
      severe. Strategies to correct hypoxemia have the potential to improve clinical
      outcomes in ARDS. The goal of this study was to evaluate the potential of
      hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. The
      therapeutic effect of two different doses of GBT1118, a compound that increases
      the oxygen affinity of hemoglobin, was evaluated in a murine model of acute lung
      injury induced by intratracheal LPS instillation 24 h before exposure to 5% or
      10% hypoxia ( n = 8-15 per group). As expected, administration of GBT1118 to mice
      significantly increased the oxygen affinity of hemoglobin. Compared with mice
      receiving vehicle control, mice treated with GBT1118 had significantly lower
      mortality after LPS + 5% hypoxia (47% with vehicle vs. 22% with low-dose GBT1118,
      13% with high-dose GBT1118, P = 0.032 by log rank) and had reduced severity of
      illness. Mice treated with GBT1118 showed a sustained significant increase in
      SpO2 over 4 h of hypoxia exposure. Treatment with GBT1118 did not alter alveolar
      capillary permeability, bronchoalveolar lavage (BAL) inflammatory cell counts, or
      BAL concentrations of IL-1beta, TNF-alpha, or macrophage inflammatory protein
      1alpha. High-dose GBT1118 did not affect histological lung injury but did
      decrease tissue hypoxia as measured intensity of pimonidazole (Hypoxyprobe)
      staining in liver ( P = 0.043) and kidney ( P = 0.043). We concluded that
      increasing the oxygen affinity of hemoglobin using GBT1118 may be a novel therapy
      for treating hypoxemia associated with acute lung injury. NEW & NOTEWORTHY In
      this study, we show that GBT1118, a compound that increases hemoglobin affinity
      for oxygen, improves survival and oxygen saturation in a two-hit lung injury
      model of intratracheal LPS without causing tissue hypoxia. Modulation of
      hemoglobin oxygen affinity represents a novel therapeutic approach to treatment
      of acute lung injury and acute respiratory distress syndrome, conditions
      characterized by hypoxemia.

PMID- 29357511
TI  - AltitudeOmics: effect of reduced barometric pressure on detection of
      intrapulmonary shunt, pulmonary gas exchange efficiency, and total pulmonary
      resistance.
AB  - Blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) occurs in
      healthy humans at rest and during exercise when breathing hypoxic gas mixtures at
      sea level and may be a source of right-to-left shunt. However, at high altitudes,
      QIPAVA is reduced compared with sea level, as detected using transthoracic saline
      contrast echocardiography (TTSCE). It remains unknown whether the reduction in
      QIPAVA (i.e., lower bubble scores) at high altitude is due to a reduction in
      bubble stability resulting from the lower barometric pressure (PB) or represents
      an actual reduction in QIPAVA. To this end, QIPAVA, pulmonary artery systolic
      pressure (PASP), cardiac output (QT), and the alveolar-to-arterial oxygen
      difference (AaDO2) were assessed at rest and during exercise (70-190 W) in the
      field (5,260 m) and in the laboratory (1,668 m) during four conditions:
      normobaric normoxia (NN; [Formula: see text] = 121 mmHg, PB = 625 mmHg; n = 8),
      normobaric hypoxia (NH; [Formula: see text] = 76 mmHg, PB = 625 mmHg; n = 7),
      hypobaric normoxia (HN; [Formula: see text] = 121 mmHg, PB = 410 mmHg; n = 8),
      and hypobaric hypoxia (HH; [Formula: see text] = 75 mmHg, PB = 410 mmHg; n = 7).
      We hypothesized QIPAVA would be reduced during exercise in isooxic hypobaria
      compared with normobaria and that the AaDO2 would be reduced in isooxic hypobaria
      compared with normobaria. Bubble scores were greater in normobaric conditions,
      but the AaDO2 was similar in both isooxic hypobaria and normobaria. Total
      pulmonary resistance (PASP/QT) was elevated in HN and HH. Using mathematical
      modeling, we found no effect of hypobaria on bubble dissolution time within the
      pulmonary transit times under consideration (<5 s). Consequently, our data
      suggest an effect of hypobaria alone on pulmonary blood flow. NEW & NOTEWORTHY
      Blood flow through intrapulmonary arteriovenous anastomoses, detected by
      transthoracic saline contrast echocardiography, was reduced during exercise in
      acute hypobaria compared with normobaria, independent of oxygen tension, whereas
      pulmonary gas exchange efficiency was unaffected. Modeling the effect(s) of
      reduced air density on contrast bubble lifetime did not result in a significantly
      reduced contrast stability. Interestingly, total pulmonary resistance was
      increased by hypobaria, independent of oxygen tension, suggesting that pulmonary
      blood flow may be changed by hypobaria.

PMID- 29357512
TI  - Involvement of cAMP/EPAC/Akt signaling in the antiproteolytic effects of
      pentoxifylline on skeletal muscles of diabetic rats.
AB  - Advances in the knowledge of the mechanisms controlling protein breakdown in
      skeletal muscles have allowed the exploration of new options for treating muscle
      wasting conditions. Pentoxifylline (PTX), a nonselective phosphodiesterase (PDE)
      inhibitor, attenuates the loss of muscle mass during catabolic conditions, mainly
      via inhibiting protein breakdown. The aim of this study was to explore the
      mechanisms by which PTX inhibits proteolysis in the soleus and extensor digitorum
      longus (EDL) muscles of streptozotocin-induced diabetic rats. The levels of
      atrogin-1 and muscle RING finger-1 were decreased, as were the activities of
      caspase-3 (EDL) and calpains (soleus and EDL), in diabetic rats treated with PTX,
      which at least partly explains the drop in the ubiquitin conjugate (EDL) levels
      and in proteasome activity (soleus and EDL). Treatment with PTX decreased PDE
      activity and increased cAMP content in muscles of diabetic rats; moreover, it
      also increased both the protein levels of exchange protein directly activated by
      cAMP (EPAC, a cAMP effector) and the phosphorylation of Akt. The loss of muscle
      mass was practically prevented in diabetic rats treated with PTX. These findings
      advance our understanding of the mechanisms underlying the antiproteolytic
      effects of PTX and suggest the use of PDE inhibitors as a strategy to activate
      cAMP signaling, which is emerging as a promising target for treating muscle mass
      loss during atrophic conditions. NEW & NOTEWORTHY cAMP signaling has been
      explored as a strategy to attenuate skeletal muscle atrophies. Therefore, in
      addition to beta2AR agonists, phosphodiesterase inhibitors such as pentoxifylline
      (PTX) can be an interesting option. This study advances the understanding of the
      mechanisms related to the antiproteolytic effects of PTX on skeletal muscles of
      diabetic rats, which involve the activation of both exchange protein directly
      activated by cAMP and Akt effectors, inhibiting the expression of atrogenes and
      calpain/caspase-3-proteolytic machinery.

PMID- 29357514
TI  - Voluntary exercise slows breast tumor establishment and reduces tumor hypoxia in
      ApoE-/- mice.
AB  - Exercise reduces the risk of breast cancer development and improves survival in
      breast cancer patients. However, the underlying mechanisms of this protective
      effect remain to be fully elucidated, and it is unclear whether exercise can
      attenuate the protumor effects of obesity and related hyperlipidemia on breast
      cancer growth and development. We hypothesized that exercise attenuates the
      negative effect of hyperlipidemia through normalization of the tumor
      microenvironment and improved T cell infiltrate. Hyperlipidemic ApoE-/- mice with
      orthotopic EO771 breast tumors were randomly assigned to one of two voluntary
      running groups or sedentary controls, and muscular cytochrome c oxidase subunit
      IV (COX-IV) expression was used as a biomarker for the level of exercise. Tumors
      from mice with high muscular COX-IV expression took significantly longer to reach
      100 mm3 ( P = 0.008), but showed no difference in growth rate once the tumor was
      established. Wheel running appeared to reduce internal metastases, but did not
      affect T cell infiltrate or the proportion of regulatory and cytotoxic T cells
      within the tumor. Serum levels of monocyte chemoattractant protein-1 (MCP-1) were
      significantly increased by tumor burden ( P = 0.02) and correlated with spleen
      weight ( P < 0.0001, R = 0.65). Furthermore, tumor hypoxia was significantly
      decreased in mice with high muscular COX-IV expression ( P = 0.01). Taken
      together, these results indicate that wheel running can slow the establishment of
      primary and secondary EO771 breast tumors and induce beneficial changes in the
      breast tumor microenvironment in ApoE-/- mice. NEW & NOTEWORTHY In this first
      study to investigate the effect of exercise on tumor behavior in a hyperlipidemic
      model, we hypothesized that wheel running would counteract the protumorigenic
      environment generated by hyperlipidemia. Wheel running slowed establishment of
      primary and secondary tumors and reduced tumor hypoxia but did not affect
      exponential tumor growth in ApoE-/- mice. Overall, voluntary wheel running
      induced favorable microenvironmental changes in breast tumors.

PMID- 29357513
TI  - The effects of age and sex on mechanical ventilatory constraint and dyspnea
      during exercise in healthy humans.
AB  - We examined the effects of age, sex, and their interaction on mechanical
      ventilatory constraint and dyspnea during exercise in 22 older (age = 68 +/- 1
      yr; n = 12 women) and 22 younger (age = 25 +/- 1 y, n = 11 women) subjects.
      During submaximal exercise, older subjects had higher end-inspiratory (EILV) and
      end-expiratory (EELV) lung volumes than younger subjects (both P < 0.05). During
      maximal exercise, older subjects had similar EILV ( P > 0.05) but higher EELV
      than younger subjects ( P < 0.05). No sex differences in EILV or EELV were
      observed. We noted that women had a higher work of breathing (Wb) for a given
      minute ventilation (Ve) >=65 l/min than men ( P < 0.05) and older subjects had a
      higher Wb for a given Ve >=60 l/min ( P < 0.05). No sex or age differences in Wb
      were present at any submaximal relative Ve. At absolute exercise intensities,
      older women experienced expiratory flow limitation (EFL) more frequently than
      older men ( P < 0.05), and older subjects were more likely to experience EFL than
      younger subjects ( P < 0.05). At relative exercise intensities, women and older
      individuals experienced EFL more frequently than men and younger individuals,
      respectively (both P < 0.05). There were significant effects of age, sex, and
      their interaction on dyspnea intensity during exercise at absolute, but not
      relative, intensities (all P < 0.05). Across subjects, dyspnea at 80 W was
      significantly correlated with indexes of mechanical ventilatory constraint (all P
      < 0.05). Collectively, our findings suggest age and sex have significant impacts
      on Wb, operating lung volumes, EFL, and dyspnea during exercise. Moreover, it
      appears that mechanical ventilatory constraint may partially explain sex
      differences in exertional dyspnea in older individuals. NEW & NOTEWORTHY We found
      that age and sex have a significant effect on mechanical ventilatory constraint
      and the perception of dyspnea during exercise. We also observed that the
      perception of exertional dyspnea is associated with indexes of mechanical
      ventilatory constraint. Collectively, our results suggest that the combined
      influences of age and biological sex on mechanical ventilatory constraint during
      exercise contributes, in part, to the increased perception of dyspnea during
      exercise in older women.

PMID- 29357515
TI  - The noninvasive simultaneous measurement of tissue oxygenation and microvascular
      hemodynamics during incremental handgrip exercise.
AB  - Limb blood flow increases linearly with exercise intensity; however, invasive
      measurements of muscle microvascular blood flow during incremental exercise have
      demonstrated submaximal plateaus. We tested the hypotheses that 1) brachial
      artery blood flow (QBA) would increase with increasing exercise intensity until
      task failure, 2) blood flow index of the flexor digitorum superficialis (BFIFDS)
      measured noninvasively via diffuse correlation spectroscopy would plateau at a
      submaximal work rate, and 3) muscle oxygenation characteristics (total-[heme],
      deoxy-[heme], and percentage saturation) measured noninvasively with near
      infrared spectroscopy would demonstrate a plateau at a similar work rate as
      BFIFDS. Sixteen subjects (23.3 +/- 3.9 yr, 170.8 +/- 1.9 cm, 72.8 +/- 3.4 kg)
      participated in this study. Peak power (Ppeak) was determined for each subject
      (1.8 +/- 0.4 W) via an incremental handgrip exercise test. QBA, BFIFDS, total
      [heme], deoxy-[heme], and percentage saturation were measured during each stage
      of the exercise test. On a subsequent testing day, muscle activation measurements
      of the FDS (RMSFDS) were collected during each stage of an identical incremental
      handgrip exercise test via electromyography from a subset of subjects ( n = 7).
      QBA increased with exercise intensity until the final work rate transition ( P <
      0.05). No increases in BFIFDS or muscle oxygenation characteristics were observed
      at exercise intensities greater than 51.5 +/- 22.9% of Ppeak. No submaximal
      plateau in RMSFDS was observed. Whereas muscle activation of the FDS increased
      until task failure, noninvasively measured indices of perfusive and diffusive
      muscle microvascular oxygen delivery demonstrated submaximal plateaus. NEW &
      NOTEWORTHY Invasive measurements of muscle microvascular blood flow during
      incremental exercise have demonstrated submaximal plateaus. We demonstrate that
      indices of perfusive and diffusive microvascular oxygen transport to skeletal
      muscle, measured completely noninvasively, plateau at submaximal work rates
      during incremental exercise, even though limb blood flow and muscle recruitment
      continued to increase.

PMID- 29357516
TI  - Effects of -12 degrees  head-down tilt with and without elevated levels of CO2 on
      cognitive performance: the SPACECOT study.
AB  - Microgravity and elevated levels of CO2 are two common environmental stressors in
      spaceflight that may affect cognitive performance of astronauts. In this
      randomized, double-blind, crossover trial (SPACECOT), 6 healthy males (mean +/-
      SD age: 41 +/- 5 yr) were exposed to 0.04% (ambient air) and 0.5% CO2
      concentrations during 26.5-h periods of -12 degrees  head-down tilt (HDT) bed
      rest with a 1-wk washout period between exposures. Subjects performed the 10
      tests of the Cognition Test Battery before and on average 0.1, 5.2, and 21.0 h
      after the initiation of HDT bed rest. HDT in ambient air induced a change in
      response strategy, with increased response speed (+0.19 SD; P = 0.0254) at the
      expense of accuracy (-0.19 SD; P = 0.2867), resulting in comparable cognitive
      efficiency. The observed effects were small and statistically significant for
      cognitive speed only. However, even small declines in accuracy can potentially
      cause errors during mission-critical tasks in spaceflight. Unexpectedly, exposure
      to 0.5% CO2 reversed the response strategy changes observed under HDT in ambient
      air. This was possibly related to hypercapnia-induced cerebrovascular reactivity
      that favors cortical regions in general and the frontal cortex in particular, or
      to the CNS arousing properties of mildly to moderately increased CO2 levels.
      There were no statistically significant time-in-CO2 effects for any cognitive
      outcome. The small sample size and the small effect sizes are major limitations
      of this study and its findings. The results should not be generalized beyond the
      group of investigated subjects until they are confirmed by adequately powered
      follow-up studies. NEW & NOTEWORTHY Simulating microgravity with exposure to 21 h
      of -12 degrees  head-down tilt bed rest caused a change in response strategy on a
      range of cognitive tests, with a statistically significant increase in response
      speed at the expense of accuracy. Cognitive efficiency was not affected. The
      observed speed-accuracy tradeoff was small but may nevertheless be important for
      mission-critical tasks in spaceflight. Importantly, the change in response
      strategy was reversed by increasing CO2 concentrations to 0.5%.

PMID- 29357517
TI  - Motor unit territories in human genioglossus estimated with multichannel
      intramuscular electrodes.
AB  - The discharge patterns of genioglossus motor units during breathing have been
      well-characterized in previous studies, but their localization and territories
      are not known. In this study, we used two newly developed intramuscular
      multichannel electrodes to estimate the territories of genioglossus motor units
      in the anterior and posterior regions of the muscle. Seven healthy men
      participated. Each electrode contained fifteen bipolar channels, separated by 1
      mm, and was inserted percutaneously below the chin, perpendicular to the skin, to
      a depth of 36 mm. Single motor unit activity was recorded with subjects awake,
      supine, and breathing quietly through a nasal mask for 180 s. Motor unit
      territories were estimated from the spike-triggered averages of the
      electromyographic signal from each channel. A total of 30 motor units were
      identified: 22 expiratory tonic, 1 expiratory phasic, 2 tonic, 3 inspiratory
      tonic, and 2 inspiratory phasic. Motor units appeared to be clustered based on
      unit type, with peak activities for expiratory units predominantly located in the
      anterior and superficial fibers of genioglossus and inspiratory units in the
      posterior region. Of these motor unit types, expiratory tonic units had the
      largest estimated territory, a mean 11.3 mm (SD 1.9). Estimated territories of
      inspiratory motor units ranged from 3 to 6 mm. In accordance with the
      distribution of motor unit types, the estimated territory of genioglossus motor
      units varied along the sagittal plane, decreasing from anterior to posterior. Our
      findings suggest that genioglossus motor units have large territories relative to
      the cross-sectional size of the muscle. NEW & NOTEWORTHY In this study, we used a
      new multichannel intramuscular electrode to address a fundamental property of
      human genioglossus motor units. We describe the territory of genioglossus motor
      units in the anterior and posterior regions of the muscle and show a decrease in
      territory size from anterior to posterior and that expiratory-related motor units
      have larger estimated territories than inspiratory-related motor units.

PMID- 29357518
TI  - Fiber type-specific analysis of AMPK isoforms in human skeletal muscle:
      advancement in methods via capillary nanoimmunoassay.
AB  - Human skeletal muscle is a heterogeneous mixture of multiple fiber types (FT).
      Unfortunately, present methods for FT-specific study are constrained by limits of
      protein detection in single-fiber samples. These limitations beget compensatory
      resource-intensive procedures, ultimately dissuading investigators from pursuing
      FT-specific research. Additionally, previous studies neglected hybrid FT,
      confining their analyses to only pure FT. Here we present novel methods of
      protein detection across a wider spectrum of human skeletal muscle FT using fully
      automated capillary nanoimmunoassay (CNIA) technology. CNIA allowed a ~20-fold
      lower limit of 5'-AMP-activated protein kinase (AMPK) detection compared with
      Western blotting. We then performed FT-specific assessment of AMPK expression as
      a proof of concept. Individual human muscle fibers were mechanically isolated,
      dissolved, and myosin heavy chain (MHC) fiber typed via SDS-PAGE. Single-fiber
      samples were combined in pairs and grouped into MHC I, MHC I/IIa, MHC IIa, and
      MHC IIa/IIx for expression analysis of AMPK isoforms alpha1, alpha2, beta1,
      beta2, gamma2, and gamma3 with a tubulin loading control. Significant FT-specific
      differences were found for alpha2 (1.7-fold higher in MHC IIa and MHC IIa/IIx vs.
      others), gamma2 (2.5-fold higher in MHC IIa vs. others), and gamma3 (2-fold
      higher in MHC IIa and 4-fold higher in MHC IIa/IIx vs. others). Development of a
      protocol that combines the efficient and sensitive CNIA technology with
      comprehensive SDS-PAGE fiber typing marks an important advancement in FT-specific
      research because it allows more precise study of the molecular mechanisms
      governing metabolism, adaptation, and regulation in human muscle. NEW &
      NOTEWORTHY We demonstrate the viability of applying capillary nanoimmunoassay
      technology to the study of fiber type-specific protein analysis in human muscle
      fibers. This novel technique enables a ~20-fold-lower limit of protein detection
      compared with traditional Western blotting methods. Combined with SDS-PAGE
      methods of fiber typing, we apply this technique to compare 5'-AMP-activated
      protein kinase isoform expression in myosin heavy chain (MHC) I, MHC I/IIa, MHC
      IIa, and MHC IIa/IIx fiber types.

PMID- 29357519
TI  - Enhanced basal late sodium current appears to underlie the age-related
      prolongation of action potential duration in guinea pig ventricular myocytes.
AB  - Aging hearts have prolonged QT interval and are vulnerable to oxidative stress.
      Because the QT interval indirectly reflects the action potential duration (APD),
      we examined the hypotheses that 1) the APD of ventricular myocytes increases with
      age; 2) the age-related prolongation of APD is due to an enhancement of basal
      late Na+ current (INaL); 3) inhibition of INaL may protect aging hearts from
      arrhythmogenic effects of hydrogen peroxide (H2O2). Experiments were performed on
      ventricular myocytes isolated from one-month (young) and one-year (old) guinea
      pigs (GPs). The APD of myocytes from old GPs was significantly longer than that
      from young GPs and was shortened by the INaL inhibitors GS967 and tetrodotoxin.
      The magnitude of INaL was significantly larger in myocytes from old than from
      young GPs. The CaMKII inhibitors KN-93 and AIP and the NaV1.5-channel blocker
      MTSEA blocked the INaL. There were no significant differences between myocytes
      from young and old GPs in L-type Ca2+ current and the rapidly- and slowly
      activating delayed rectifier K+ currents, although the inward rectifier K+
      current was slightly decreased in myocytes from old GPs. H2O2 induced more early
      afterdepolarizations in myocytes from old than from young GPs. The effect of H2O2
      was attenuated by GS967. The results suggest that 1) the APD of myocytes from old
      GPs is prolonged, 2) a CaMKII-mediated increase in NaV1.5-channel INaL is
      responsible for the prolongation of APD, and 3) Inhibition of INaL may be
      beneficial for maintaining electrical stability under oxidative stress in
      myocytes of old GPs.

PMID- 29357520
TI  - Unilateral strength training leads to muscle-specific sparing effects during
      opposite homologous limb immobilization.
AB  - Cross education (CE) occurs after unilateral training whereby performance of the
      untrained contralateral limb is enhanced. A few studies have shown that CE can
      preserve or "spare" strength and size of an opposite immobilized limb, but the
      specificity (i.e., trained homologous muscle and contraction type) of these
      effects is unknown. The purpose was to investigate specificity of CE "sparing"
      effects with immobilization. The nondominant forearm of 16 participants was
      immobilized with a cast, and participants were randomly assigned to a resistance
      training (eccentric wrist flexion, 3 times/week) or control group for 4 weeks.
      Pre- and posttesting involved wrist flexors and extensors eccentric, concentric
      and isometric maximal voluntary contractions (via dynamometer), muscle thickness
      (via ultrasound), and forearm muscle cross-sectional area (MCSA; via peripheral
      quantitative computed tomography). Only the training group showed strength
      preservation across all contractions in the wrist flexors of the immobilized limb
      (training: -2.4% vs. control: -21.6%; P = 0.04), and increased wrist flexors
      strength of the nonimmobilized limb (training: 30.8% vs. control: -7.4%; P =
      0.04). Immobilized arm MCSA was preserved for the training group only (training:
      1.3% vs. control: -2.3%; P = 0.01). Muscle thickness differed between groups for
      the immobilized (training: 2.8% vs. control: -3.2%; P = 0.01) and nonimmobilized
      wrist flexors (training: 7.1% vs. control: -3.7%; P = 0.02). Strength
      preservation was nonspecific to contraction type ( P = 0.69, [Formula: see text]
      = 0.03) yet specific to the trained flexors muscle. These findings suggest that
      eccentric training of the nonimmobilized limb can preserve size of the
      immobilized contralateral homologous muscle and strength across multiple
      contraction types. NEW & NOTEWORTHY Unilateral strength training preserves
      strength, muscle thickness, and muscle cross-sectional area in an opposite
      immobilized limb. The preservation of size and strength was confined to the
      trained homologous muscle group. However, strength was preserved across multiple
      contraction types.

PMID- 29357522
TI  - Point: Counterpoint Glucose Phosphorylation is/ is not a Significant Barrier to
      Muscle Glucose Uptake By the Working Muscle.

PMID- 29357521
TI  - Intermittent hypoxia in utero damages postnatal growth and cardiovascular
      function in rats.
AB  - Obstructive sleep apnea (OSA) is common in pregnancy and may compromise fetal and
      even postnatal development. We developed an animal model to determine if maternal
      OSA could have lasting effects in offspring. Pregnant Sprague-Dawley rats were
      exposed to reduced ambient O2 from 21 to 4-5%, approximately once per minute
      [chronic intermittent hypoxia (CIH)] for 8 h/day during gestation days 3-19.
      Similarly handled animals exposed to ambient air served as controls (HC).
      Offspring were studied for body growth and cardiovascular function for 8
      postnatal weeks. Compared with HC, prenatal CIH led to growth restriction,
      indicated by smaller body weight and tibial length, and higher arterial blood
      pressure in both male and female offspring. Compared with same-sex HC, CIH males
      showed abdominal obesity (greater ratio of abdominal fat weight to body weight or
      tibial length), left ventricular (LV) hypertrophy (greater heart weight-to-tibial
      length ratio and LV posterior wall diastolic thickness), elevated LV
      contractility (increases in LV ejection fraction, end-systolic pressure-volume
      relations, and preload recruitable stroke work), elevated LV and arterial
      stiffness (increased end-diastolic pressure-volume relationship and arterial
      elasticity), and LV oxidative stress (greater lipid peroxide content). Compared
      with female CIH offspring, male CIH offspring had more profound changes in blood
      pressure (BP), cardiac function, myocardial lipid peroxidase (LPO) content, and
      abdominal adiposity. Rodent prenatal CIH exposure, mimicking human maternal OSA,
      exerts detrimental morphological and cardiovascular effects on developing
      offspring; the model may provide useful insights of OSA effects in humans. NEW &
      NOTEWORTHY Obstructive sleep apnea is common in human pregnancy. Following
      maternal exposure to chronic intermittent hypoxia, a hallmark of sleep apnea,
      both sexes of rat offspring showed growth retardation, with males being more
      vulnerable to hypertension and dysfunctional left ventricular changes. This model
      is useful to study detrimental effects of maternal obstructive sleep apnea on
      developing offspring in humans.

PMID- 29357523
TI  - Re: Risk Factors for Long-Term Outcome in Photoselective Vaporization of the
      Prostate.

PMID- 29357524
TI  - Re: Metabolic Syndrome Does Not Increase the Risk of Ejaculatory Dysfunction in
      Patients with Lower Urinary Tract Symptoms and Benign Prostatic Enlargement: An
      Italian Single-Center Cohort Study.

PMID- 29357525
TI  - Re: Understanding Patient and Physician Perceptions of Benign Prostatic
      Hyperplasia in Asia Pacific, Latin America and the Commonwealth of Independent
      States: The Prostate Research on Behaviour and Education (PROBE) II Survey.

PMID- 29357526
TI  - Re: Trends in Operating Room Assistance for Major Urologic Surgical Procedures:
      An Increasing Role for Advanced Practice Providers.

PMID- 29357527
TI  - Re: Predictors of 30-Day Pulmonary Complications after Outpatient Surgery:
      Relative Importance of Body Mass Index Weight Classifications in Risk Assessment.

PMID- 29357529
TI  - Re: Presentation and Surgery Outcomes in Elderly with Pheochromocytoma: A
      Comparative Analysis with Young Patients.

PMID- 29357528
TI  - Re: Prevalence and Progression of Lower Urinary Tract Symptoms in an Aging
      Population.

PMID- 29357530
TI  - Re: Vitamin D and Incident Urinary Incontinence in Older Adults.

PMID- 29357531
TI  - Re: Active Surveillance for Incidental Renal Mass in the Octogenarian.

PMID- 29357532
TI  - Re: Influence and Impact of Cognitive Trajectories on Outcome in Patients
      Undergoing Radical Cystectomy: An Observational Study.

PMID- 29357533
TI  - Re: Pattern and Distribution of Distant Metastases in Anaplastic Prostate
      Carcinoma: A Single-Institute Experience with 101 Patients.

PMID- 29357534
TI  - Re: Efficacy of Tamsulosin, Oxybutynin, and Their Combination in the Control of
      Double-J Stent-Related Lower Urinary Tract Symptoms.

PMID- 29357535
TI  - Re: High Tech or High Risk? An Analysis of Media Reports about Robotic Surgery.

PMID- 29357536
TI  - Re: Prognostic Value of Exercise Capacity among Men Undergoing Pharmacologic
      Treatment for Erectile Dysfunction: The FIT Project.

PMID- 29357537
TI  - Re: Quality of Erections by Age Group in Men with Erectile Dysfunction.

PMID- 29357538
TI  - Re: Screening for Sexual Dissatisfaction among People with Type 2 Diabetes in
      Primary Care.

PMID- 29357539
TI  - Re: The Accuracy of Patients' Perceptions of the Risks Associated with Localised
      Prostate Cancer Treatments.

PMID- 29357540
TI  - Re: Adulteration of Proprietary Chinese Medicines and Health Products with
      Undeclared Drugs: Experience of a Tertiary Toxicology Laboratory in Hong Kong.

PMID- 29357541
TI  - Re: Risk of Diabetes According to Male Factor Infertility: A Register-Based
      Cohort Study.

PMID- 29357542
TI  - Re: Correction of a Pathogenic Gene Mutation in Human Embryos.

PMID- 29357543
TI  - Re: Sex and Gender: You Should Know the Difference.

PMID- 29357544
TI  - Re: Exercise Improved Semen Quality and Reproductive Hormone Levels in Sedentary
      Obese Adults.

PMID- 29357545
TI  - Re: High-Intensity Exercise Training for Improving Reproductive Function in
      Infertile Patients: A Randomized Controlled Trial.

PMID- 29357546
TI  - Re: Exposure to Mycophenolate and Fatherhood.

PMID- 29357547
TI  - Re: Strategies for Identifying and Closing the Gender Salary Gap in Surgery.

PMID- 29357548
TI  - Re: Medicare's Acute Care Episode Demonstration: Effects of Bundled Payments on
      Costs and Quality of Surgical Care.

PMID- 29357550
TI  - Re: Urethral Stricture Outcomes after Artificial Urinary Sphincter Cuff Erosion:
      Results from a Multicenter Retrospective Analysis.

PMID- 29357549
TI  - Re: Low Testosterone Levels Result in Decreased Periurethral Vascularity via an
      Androgen Receptor-Mediated Process: Pilot Study in Urethral Stricture Tissue.

PMID- 29357551
TI  - Re: Evidence of Disordered Calcium Metabolism in Adolescent Girls with Type 1
      Diabetes: An Observational Study Using a Dual-Stable Calcium Isotope Technique.

PMID- 29357552
TI  - Re: Surgery for Primary Hyperparathyroidism: Adherence to Consensus Guidelines in
      an Academic Health System.

PMID- 29357553
TI  - Re: Stone Growth Patterns and Risk for Surgery among Children Presenting with
      Hypercalciuria, Hypocitraturia and Cystinuria as Underlying Metabolic Causes of
      Urolithiasis.

PMID- 29357554
TI  - Re: Effectiveness of Treatment Modalities on Kidney Stone Recurrence.

PMID- 29357555
TI  - Re: saRNA-Mediated Activation of TRPV5 Reduces Renal Calcium Oxalate Deposition
      in Rat via Decreasing Urinary Calcium Excretion.

PMID- 29357556
TI  - Re: The Impact of Quality Variations on Patients Undergoing Surgery for Renal
      Cell Carcinoma: A National Cancer Database Study.

PMID- 29357557
TI  - Re: When to Perform Preoperative Chest Computed Tomography for Renal Cancer
      Staging.

PMID- 29357558
TI  - Re: Clinical Significance of Preoperative C-Reactive Protein and Squamous Cell
      Carcinoma Antigen Levels in Patients with Penile Squamous Cell Carcinoma.

PMID- 29357559
TI  - Re: The Impact of Re-Transurethral Resection on Clinical Outcomes in a Large
      Multicentre Cohort of Patients with T1 High-Grade/Grade 3 Bladder Cancer Treated
      with bacille Calmette-Guerin.

PMID- 29357560
TI  - Re: Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death
      Ligand-1 Immune Checkpoint Inhibitor, in Patients with Advanced Urothelial
      Bladder Cancer.

PMID- 29357561
TI  - Re: Follow-up of Prostatectomy versus Observation for Early Prostate Cancer.

PMID- 29357562
TI  - Re: Adverse Pathologic Findings for Men Electing Immediate Radical Prostatectomy:
      Defining a Favorable Intermediate-Risk Group.

PMID- 29357563
TI  - Re: Prognostic Value of Programmed-Death-1 Receptor (PD-1) and its Ligand 1 (PD
      L1) in Testicular Germ Cell Tumors.

PMID- 29357564
TI  - Re: mTORC1-Dependent AMD1 Regulation Sustains Polyamine Metabolism in Prostate
      Cancer.

PMID- 29357565
TI  - Re: Unifying Mechanism for Different Fibrotic Diseases.

PMID- 29357567
TI  - Re: Unravelling Detrusor Underactivity: Development of a Bladder Outlet
      Resistance-Bladder Contractility Nomogram for Adult Male Patients with Lower
      Urinary Tract Symptoms.

PMID- 29357566
TI  - Re: Analysis of Renal Cancer Cell Lines from Two Major Resources Enables Genomics
      Guided Cell Line Selection.

PMID- 29357568
TI  - Re: Tension-Free Vaginal Tape-Obturator for Treatment of Pure Urodynamic Stress
      Urinary Incontinence: Efficacy and Adverse Effects at 10-Year Follow-up.

PMID- 29357569
TI  - Re: Bladder Wall Thickness in Women with Symptoms of Overactive Bladder and
      Detrusor Overactivity: Results from the Randomised, Placebo-Controlled SHRINK
      Study.

PMID- 29357570
TI  - Re: Is Bariatric Surgery the Answer to Urinary Incontinence in Obese Women?

PMID- 29357571
TI  - Re: Interventions to Decrease Pain and Anxiety in Patients Undergoing Urodynamic
      Testing: A Randomized Controlled Trial.

PMID- 29357572
TI  - Re: Resolution of Overactive Bladder after Mid-Urethral Sling Placement with
      Mixed Incontinence.

PMID- 29357573
TI  - Re: Comprehensive Analysis of the Clinical and Urodynamic Outcomes of Primary
      Tethered Spinal Cord before and after Spinal Cord Untethering.

PMID- 29357574
TI  - Re: Urinary Proteomics Yield Pathological Insights for Ureteropelvic Junction
      Obstruction.

PMID- 29357575
TI  - Re: Comprehensive Analysis of the Clinical and Urodynamic Outcomes of Secondary
      Tethered Spinal Cord before and after Spinal Cord Untethering.

PMID- 29357576
TI  - Re: Continence and Quality of Life with the Modified Heitz-Boyer-Hovelacque
      Rectal Bladder for Children with Urinary Incontinence following Bladder
      Exstrophy.

PMID- 29357577
TI  - Re: Computer Model Predicting Breakthrough Febrile Urinary Tract Infection in
      Children with Primary Vesicoureteral Reflux.

PMID- 29357579
TI  - Sunscreen and melanoma prevention: evidence and expectations.

PMID- 29357580
TI  - Understanding common but understudied diseases in dermatology.

PMID- 29357581
TI  - Image Gallery: Bowen's disease of a nail unit presenting with 'woodgrain
      appearance' - a new dermoscopic finding.

PMID- 29357582
TI  - Image Gallery: Lenalidomide for the treatment of pseudotumoral herpes simplex
      virus type 2 infection in human immunodeficiency virus infection.

PMID- 29357583
TI  - Corrigenda.

PMID- 29357584
TI  - Indirubin: a novel topical agent in the treatment of psoriasis.

PMID- 29357585
TI  - Driver mutations in the mitogen-activated protein kinase pathway: the seeds of
      good and evil.

PMID- 29357587
TI  - Biologic treatment for psoriasis and cancer: an increased risk for most cancers
      could not be ruled out.

PMID- 29357586
TI  - Treatment success in cutaneous warts: morphology and human papillomavirus type
      matter.

PMID- 29357589
TI  - Progress in the diagnosis and therapy of melanoma.

PMID- 29357590
TI  - The benefit of nested qualitative studies in dermatology randomized controlled
      trials.

PMID- 29357592
TI  - Patients with psoriasis on a new trajectory: long-term improvement in quality of
      life with biologics.

PMID- 29357593
TI  - When to switch biologics: some answers, but lots of questions too.

PMID- 29357594
TI  - Corrigenda.

PMID- 29357595
TI  - Corrigenda.

PMID- 29357596
TI  - A new era in holistic care: bridging the gap between dermatologists and
      oncologists for the treatment of malignant melanoma.

PMID- 29357597
TI  - Pigmentary evolution with pembrolizumab use.

PMID- 29357598
TI  - Cover Image: Blisters owing to dermal capillary occlusion by sickle cells.

PMID- 29357599
TI  - Vitiligo and quality of life: the dark face of whiteness.

PMID- 29357601
TI  - Corrigenda.

PMID- 29357602
TI  - What can we learn from psoriasis pharmacogenomics research?

PMID- 29357600
TI  - British Association of Dermatologists' guidelines for the investigation and
      management of generalized pruritus in adults without an underlying dermatosis,
      2018.

PMID- 29357603
TI  - T-QoL: a quality of life outcome measure specifically developed for adolescents
      with skin diseases.

PMID- 29357604
TI  - Image Gallery: Immunohistochemical detection of parvovirus B19 VP2 in
      periflexural primary infection in an adult female patient.

PMID- 29357605
TI  - Image Gallery: A case of malignant syphilis in an HIV-infected patient mimicking
      fungal infection.

PMID- 29357606
TI  - Cutaneous manifestations of paediatric Erdheim-Chester disease, a histiocytosis
      of the 'L' group.

PMID- 29357607
TI  - How breakthroughs in translational research have impacted treatment strategies
      for melanoma.

PMID- 29357608
TI  - Yet another step forward!

PMID- 29357609
TI  - Image Gallery: Pyoderma gangrenosum of the penis.

PMID- 29357610
TI  - Corrigenda.

PMID- 29357612
TI  - Advances in the diagnosis of pigmented skin lesions.

PMID- 29357611
TI  - Growing evidence for coronary artery disease risk factors in patients with severe
      hidradenitis suppurativa.

PMID- 29357613
TI  - Assessing the safety of new drugs during pregnancy.

PMID- 29357614
TI  - Introduction to Endoscopic Submucosal Surgery.
AB  - The concept of using natural orifices to reduce the complications of surgery,
      Natural Orifices Transluminal Endoscopic Surgery, has also been applied to
      therapeutic endoscopy. Endoscopic submucosal surgery (ESS) provides more
      treatment options for various gastrointestinal diseases than traditional
      therapeutic endoscopy by using the submucosal layer as a working space. ESS has
      been performed in various fields ranging from transluminal peritoneoscopy to
      peroral endoscopic myotomy. With further advances in technology, ESS will be
      increasingly useful for diagnosis and treatment of gastrointestinal diseases.

PMID- 29357615
TI  - The biology of marginalization.

PMID- 29357616
TI  - ?

PMID- 29357617
TI  - Doctors' time for working with patients and patients' time with doctors.

PMID- 29357618
TI  - [Not Available].

PMID- 29357619
TI  - ?

PMID- 29357620
TI  - ?

PMID- 29357622
TI  - ?

PMID- 29357621
TI  - ?

PMID- 29357623
TI  - ?

PMID- 29357624
TI  - ?

PMID- 29357625
TI  - ?

PMID- 29357627
TI  - ?

PMID- 29357626
TI  - ?

PMID- 29357628
TI  - ?

PMID- 29357629
TI  - ?

PMID- 29357630
TI  - The right to a health-promoting diet for people with intellectual disabilities.

PMID- 29357631
TI  - ?

PMID- 29357632
TI  - ?

PMID- 29357633
TI  - ?

PMID- 29357635
TI  - ?

PMID- 29357634
TI  - ?

PMID- 29357636
TI  - ?

PMID- 29357637
TI  - ?

PMID- 29357638
TI  - ?

PMID- 29357639
TI  - ?

PMID- 29357640
TI  - ?

PMID- 29357641
TI  - ?

PMID- 29357642
TI  - ?

PMID- 29357643
TI  - ?

PMID- 29357644
TI  - ?

PMID- 29357645
TI  - ?

PMID- 29357646
TI  - ?

PMID- 29357647
TI  - ?

PMID- 29357648
TI  - ?

PMID- 29357650
TI  - ?

PMID- 29357649
TI  - ?

PMID- 29357651
TI  - ?

PMID- 29357652
TI  - ?

PMID- 29357653
TI  - Drug treatment of ADHD - tenuous scientific basis.

PMID- 29357655
TI  - ?

PMID- 29357654
TI  - ?

PMID- 29357656
TI  - ?

PMID- 29357657
TI  - When doctors serve as experts.

PMID- 29357658
TI  - Implementing a birth registry in a developing country - experiences from Georgia.
AB  - BACKGROUND: Georgia is the first developing country in the world to have
      established a national digital, medical birth registry. The Georgia Birth
      Registry was officially inaugurated on 1 January, 2016. The purpose of this
      article is to assess the quality of selected variables and present preliminary
      results from the year 2016. MATERIAL AND METHODS: The Registry resembles the
      Nordic birth registries in structure. There are 285 medical facilities involved,
      each entering 267 variables from week 12 of pregnancy to hospital discharge. In
      2016, 52 399 women and 53 236 newborns were recorded as valid entries in the
      Georgian Birth Registry. RESULTS: The completeness of the Registry in 2016 was
      93.9 %. The difference between the reported number of newborns in the Registry
      and in official statistics was 3441. The mean gestational age was 271.3 days and
      the Caesarean section rate 43.5 %. The mean birth weight was 3262 g. Newborns
      delivered by Caesarean section had a lower gestational age and lower birth weight
      compared to those delivered vaginally. INTERPRETATION: There are more newborns
      registered annually as Georgian citizens than the number of infants born in the
      country. This leads to inaccurate official reporting on perinatal mortality
      rates.

PMID- 29357659
TI  - ?

PMID- 29357660
TI  - The archive is everywhere.

PMID- 29357662
TI  - ?

PMID- 29357661
TI  - [Not Available].

PMID- 29357663
TI  - ?

PMID- 29357664
TI  - Synthesis and Characterization of Electron-Deficient Asymmetrically Substituted
      Diarylindenotetracenes.
AB  - Electron-deficient asymmetrically substituted diarylindenotetracenes were
      prepared via a series of Friedel-Crafts acylations, aryl-aryl cross-couplings,
      and an intramolecular oxidative cyclization to form the indene ring. Single
      crystal X-ray experiments showed good pi-pi overlap with pi-pi distances ranging
      from 3.26 to 3.76 A. Both thermogravimetric analysis and differential scanning
      calorimetry indicated that asymmetrically substituted indenotetracenes (ASIs) are
      stable at elevated temperatures. From cyclic voltammetry experiments, HOMO/LUMO
      energy levels of ASI derivatives were determined to be near -5.4/-4.0 eV.
      UV/visible absorption spectra showed strong absorption of light between 400 and
      650 nm with molar attenuation coefficients from 104 to 105 M-1 cm-1. ASIs were
      also found to have very low fluorescence quantum yields, less than 4%. Using the
      solid-state packing determined from the single-crystal X-ray experiments,
      computational modeling indicated that ASI molecules should favor electron
      transport.

PMID- 29357665
TI  - Thioesterase-Mediated Synthesis of Teixobactin Analogues: Mechanism and Substrate
      Specificity.
AB  - A chemoenzymatic approach for the synthesis of teixobactin analogues has been
      established by using the tandem thioesterase (TE) of the nonribosomal peptide
      synthase (NRPS) Txo2. We show that, unlike the closely related counterparts
      involved in lysobactin biosynthesis (in which the N-terminal TE is solely
      responsible for the lactonization reaction), the two teixobactin TE domains are
      functionally exchangeable and likely act synergistically, representing an
      unprecedented off-loading mechanism in NRPS enzymology. The substrate specificity
      of this tandem TE was also investigated in this study.

PMID- 29357666
TI  - The Conformation and Aggregation of Proline-Rich Surfactant-Like Peptides.
AB  - The secondary structure of proline-rich surfactant-like peptides is examined for
      the first time and is found to be influenced by charged end groups in peptides
      P6K, P6E, and KP6E and an equimolar mixture of P6K and P6E. The peptides exhibit
      a conformational transition from unordered to polyproline II (PPII) above a
      critical concentration, detected from circular dichroism (CD) measurements and
      unexpectedly from fluorescence dye probe measurements. Isothermal titration
      calorimetry (ITC) measurements provided the Gibbs energies of hydration of P6K
      and P6E, which correspond essentially to the hydration energies of the terminal
      charged residues. A detailed analysis of peptide conformation for these peptides
      was performed using density functional theory calculations, and this was used as
      a basis for hybrid quantum mechanics/molecular mechanics molecular dynamics
      (QM/MM MD) simulations. Quantum mechanics simulations in implicit water show both
      peptides (and their 1:1 mixture) exhibit PPII conformations. However, hybrid
      QM/MM MD simulations suggest that some deviations from this conformation are
      present for P6K and P6E in peptide bonds close to the charged residue, whereas in
      the 1:1 mixture a PPII structure is observed. Finally, aggregation of the
      peptides was investigated using replica exchange molecular dynamics simulations.
      These reveal a tendency for the average aggregate size (as measured by the radius
      of gyration) to increase with increasing temperature, which is especially marked
      for P6K, although the fraction of the most populated clusters is larger for P6E.

PMID- 29357668
TI  - Announcing the 2018 ACS Nano Lectureship Awards.

PMID- 29357667
TI  - Preface to the Early Career Authors in Fundamental Colloid and Interface Science
      Special Issue.

PMID- 29357669
TI  - In Nano, Volume 12, Issue 1.

PMID- 29357670
TI  - Compensation Strategies in Older Adults: Association With Cognition and Everyday
      Function.
AB  - BACKGROUND/RATIONALE: Compensation strategies may contribute to greater
      resilience among older adults, even in the face of cognitive decline. This study
      sought to better understand how compensation strategy use among older adults with
      varying degrees of cognitive impairment impacts everyday functioning. METHODS: In
      all, 125 older adults (normal cognition, mild cognitive impairment, dementia)
      underwent neuropsychological testing, and their informants completed
      questionnaires regarding everyday compensation and cognitive and functional
      abilities. RESULTS: Cognitively normal and mild cognitive impairment older adults
      had greater levels of compensation use than those with dementia. Higher levels of
      neuropsychological functioning were associated with more frequent compensation
      use. Most importantly, greater frequency of compensation strategy use was
      associated with higher levels of independence in everyday function, even after
      accounting for cognition. CONCLUSION: Use of compensation strategies is
      associated with higher levels of functioning in daily life among older adults.
      Findings provide strong rational for development of interventions that directly
      target such strategies.

PMID- 29357671
TI  - The management of young people who self-harm by New Zealand Infant, Child and
      Adolescent Mental Health Services: cutting-edge or cutting corners?
AB  - OBJECTIVES: Self-harm is common in New Zealand (NZ) young people and can have
      short-term and long-term consequences, including suicide. This study was
      undertaken to examine the extent to which evidence-based approaches for
      addressing self-harm are offered by Infant, Child and Adolescent Mental Health
      Services (ICAMHS). METHODS: A national survey of ICAMHS practitioners working
      with young people who self-harm was undertaken between May and July 2016.
      RESULTS: Responses from 23 out of 30 ICAMHS confirmed self-harm was a familiar
      presentation and most commonly associated with diagnoses of depression, anxiety
      and borderline personality disorder. Cognitive behavioural therapy (47.1%, n =
      8), dialectical behaviour therapy (47.1%, n = 8) and acceptance and commitment
      therapy (5.9%, n = 1) were the treatments of choice, but variably delivered.
      There were significant training gaps for all types of therapy. CONCLUSIONS:
      Although it is reassuring that many ICAMHS are using evidence-based approaches to
      address self-harm in young people, there is concerning variability in the way
      these therapies are delivered. Improvement in training in key modalities, further
      research into therapist performance and continuous evaluation of workforce
      development are needed to maximise the effectiveness of proven interventions and
      provide NZ young people with the state-of-the-art service they deserve.

PMID- 29357672
TI  - Age- and Occupation-Based Public Health Considerations Related to Osteoarthritis
      of the Knee Joint: A Cadaveric Study.
AB  - OBJECTIVE: Osteoarthritis (OA) literature makes minimal suggestion regarding age
      of disease onset or preventative strategies to reduce risk for onset in various
      populations. In 2005, the Centers for Disease Control and Prevention estimated
      that 33.6% of Americans 65+ years old were affected by OA; this cadaveric
      analysis suggests this is largely underestimated. The objective of this
      assessment is to identify at-risk populations for OA in the knee joint and make
      recommendations to prevent or delay disease onset. DESIGN: Morphometric analyses
      of the articular cartilage of the tibial plateau were performed on cadaver
      specimens using Image Pro software on 3 age populations and surface area
      measurements for articular cartilage degradation were compared with donors'
      reported ages, clinical histories, and occupations. RESULTS: Data showed that by
      the seventh decade of life, when patients are in their 60s, articular cartilage
      degeneration on the tibial plateau had commenced in 100% of specimen. All
      "homemakers" displayed above-average medial tibial plateau degeneration (32.33%
      +/- 24.85%) for their age group while simultaneously reporting pathologies in
      their clinical history that encourage a sedentary lifestyle. CONCLUSIONS: This
      assessment identifies an occupational class with a propensity to develop disease
      and also identifies a more realistic time frame than previous advisory committees
      have produced regarding age of disease onset and initiation of preventative
      measures. It is recommended that strengthening of the hip abductors and the
      musculature supporting the knee commence early in adult life to avoid valgus
      collapse and shearing at the knee joint.

PMID- 29357673
TI  - Calcium Release Mediated by Redox-Sensitive RyR2 Channels Has a Central Role in
      Hippocampal Structural Plasticity and Spatial Memory.
AB  - AIMS: Previous studies indicate that hippocampal synaptic plasticity and spatial
      memory processes entail calcium release from intracellular stores mediated by
      ryanodine receptor (RyR) channels. In particular, RyR-mediated Ca2+ release is
      central for the dendritic spine remodeling induced by brain-derived neurotrophic
      factor (BDNF), a neurotrophin that stimulates complex signaling pathways leading
      to memory-associated protein synthesis and structural plasticity. To examine if
      upregulation of ryanodine receptor type-2 (RyR2) channels and the spine
      remodeling induced by BDNF entail reactive oxygen species (ROS) generation, and
      to test if RyR2 downregulation affects BDNF-induced spine remodeling and spatial
      memory. RESULTS: Downregulation of RyR2 expression (short hairpin RNA [shRNA]) in
      primary hippocampal neurons, or inhibition of nitric oxide synthase (NOS) or
      NADPH oxidase, prevented agonist-mediated RyR-mediated Ca2+ release, whereas BDNF
      promoted cytoplasmic ROS generation. RyR2 downregulation or inhibitors of N
      methyl-d-aspartate (NMDA) receptors, or NOS or of NADPH oxidase type-2 (NOX2)
      prevented RyR2 upregulation and the spine remodeling induced by BDNF, as did
      incubation with the antioxidant agent N-acetyl l-cysteine. In addition,
      intrahippocampal injection of RyR2-directed antisense oligodeoxynucleotides,
      which caused significant RyR2 downregulation, caused conspicuous defects in a
      memorized spatial memory task. INNOVATION: The present novel results emphasize
      the key role of redox-sensitive Ca2+ release mediated by RyR2 channels for
      hippocampal structural plasticity and spatial memory. CONCLUSION: Based on these
      combined results, we propose (i) that BDNF-induced RyR2-mediated Ca2+ release and
      ROS generation via NOS/NOX2 are strictly required for the dendritic spine
      remodeling and the RyR2 upregulation induced by BDNF, and (ii) that RyR2 channel
      expression is crucial for spatial memory processes. Antioxid. Redox Signal. 29,
      1125-1146.

PMID- 29357674
TI  - Associating Symptom Phenotype and Genotype in Preeclampsia.
AB  - Preeclampsia is a complex genetic disorder with an incompletely understood
      pathogenesis. Its phenotype may be better elucidated by integrating symptoms.
      This study aimed to identify symptoms by gestational age and associations with
      novel preeclampsia candidate genes. Women with a history of preeclampsia
      recruited from The Preeclampsia Registry completed clinical/demographic, symptom
      surveys and provided medical records. DNA extracted from saliva was processed
      with multiplexed assays for eight single-nucleotide polymorphisms (SNPs) selected
      to tag candidate genes and/or located in symptom susceptibility regions. Groups
      with versus without symptoms were compared using chi2. Associations between SNPs
      and symptoms were analyzed as genotype categories and presence/absence of the
      variant allele. Logistic regression modeling was conducted with exploratory p =
      .05. In 114 participants, 113 reported at least 1 of the 18 symptoms. Symptoms
      varied by trimester. Nine symptoms were associated with seven SNPs. Visual
      disturbances were associated with three SNPs and nausea/vomiting with two SNPs.
      Modeling adjustment for maternal age and parity resulted in 15 associations
      between 9 symptoms and 8 SNPs. Medical records demonstrated 100% concordance with
      self-reported diagnosis and 48% concordance with reported severity. Findings
      indicated novel symptom-genotype associations in preeclampsia. The small sample
      was self-selected, but results support future studies including medical records
      review. When validated, these results may lead to holistic phenotyping of women
      to characterize subsets of preeclampsia. This approach may optimize health in
      pregnancy and later life for mothers and offspring through prediction,
      prevention, and precision nursing care.

PMID- 29357676
TI  - Difference of seasonal variation between glycated albumin and glycated
      haemoglobin.
AB  - Background Glycated albumin reflects 2-3-week glycaemic controls, and in addition
      to glycated haemoglobin, it has been used as a glycaemic control indicator. We
      presumed that glycated albumin also has seasonal variations and is related to
      temperature, similar to glycated haemoglobin. Methods The subjects were diabetic
      outpatients from April 2007 to March 2013. This resulted in the enrolment of 2246
      subjects and the collection of a total of 53,968 measurements. Mean glycated
      haemoglobin, glycated albumin, and plasma glucose were calculated for each month
      over six years. The associations of the measures with each other and the average
      temperature for each month in Tokyo were assessed using Spearman rank correlation
      coefficients. Results Plasma glucose was highest in January and lowest in May.
      Glycated haemoglobin was highest in March and lowest in September. Glycated
      albumin was highest in May and lowest in December. Glycated albumin tended to
      have a disjunction with plasma glucose in winter. Glycated haemoglobin had
      seasonal variation, but glycated albumin did not. Plasma glucose and glycated
      haemoglobin showed significant negative correlations with temperature (rs = 
      0.359, P < 0.001, rs = -0.449, P < 0.001, respectively), but glycated albumin did
      not. However, glycated albumin was inter-correlated with plasma glucose (rs =
      0.396, P < 0.001) and glycated haemoglobin (rs = 0.685, P < 0.001), and glycated
      haemoglobin was inter-correlated with plasma glucose (rs = 0.465, P < 0.001).
      Conclusion Glycated albumin and glycated haemoglobin showed different seasonal
      variations from each other over the six-year study period. Thus, further studies
      to identify factors that contribute to glycated albumin are needed.

PMID- 29357675
TI  - Stuck in a State of Inattention? Functional Hyperconnectivity as an Indicator of
      Disturbed Intrinsic Brain Dynamics in Adolescents With Concussion: A Pilot Study.
AB  - Sports-related concussion in youth is a major public health issue. Evaluating the
      diffuse and often subtle changes in structure and function that occur in the
      brain, particularly in this population, remains a significant challenge. The goal
      of this pilot study was to evaluate the relationship between the intrinsic
      dynamics of the brain using resting-state functional magnetic resonance imaging
      (rs-fMRI) and relate these findings to structural brain correlates from diffusion
      tensor imaging in a group of adolescents with sports-related concussions ( n = 6)
      and a group of healthy adolescent athletes ( n = 6). We analyzed rs-fMRI data
      using a sliding windows approach and related the functional findings to
      structural brain correlates by applying graph theory analysis to the diffusion
      tensor imaging data. Within the resting-state condition, we extracted three
      separate brain states in both groups. Our analysis revealed that the brain
      dynamics in healthy adolescents was characterized by a dynamic pattern, shifting
      equally between three brain states; however, in adolescents with concussion, the
      pattern was more static with a longer time spent in one brain state. Importantly,
      this lack of dynamic flexibility in the concussed group was associated with
      increased nodal strength in the left middle frontal gyrus, suggesting
      reorganization in a region related to attention. This preliminary report shows
      that both the intrinsic brain dynamics and structural organization are altered in
      networks related to attention in adolescents with concussion. This first report
      in adolescents will be used to inform future studies in a larger cohort.

PMID- 29357677
TI  - Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with
      hepatocellular carcinoma.
AB  - Background It has been reported that both of the miR-132/212 (micro-RNA) cluster
      members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma.
      Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in
      hepatocellular carcinoma are still unknown. Methods In this study, serum
      concentrations of miR-132 and miR-212 were measured in 80 hepatocellular
      carcinoma patients, 51 controls with chronic liver diseases and 42 healthy
      volunteers by using quantitative real-time polymerase chain reaction. Results In
      hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212
      were significantly reduced and strongly correlated (r = 0.603, p < 0.001).
      Receiver operator characteristic analyses showed that serum miR-132 and miR-212
      might have a potential role in the diagnosis of hepatocellular carcinoma.
      Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein
      improved the diagnostic efficiency for hepatocellular carcinoma, especially in
      sensitivity and negative predictive value. Serum miR-132 was associated with
      tumour differentiation degree ( p = 0.021) and tumour-node-metastasis stage ( p =
      0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour-node
      metastasis stage ( p = 0.007). Kaplan-Meier analyses indicated poorer overall
      survival in hepatocellular carcinoma patients with lower serum concentrations of
      miR-132 ( p < 0.001) and miR-212 ( p = 0.005). Conclusions Our results suggest
      that both components of the miR-132/212 cluster have potential roles as non
      invasive serum biomarkers for diagnosis and prognosis of hepatocellular
      carcinoma.

PMID- 29357678
TI  - Falsely elevated plasma metanephrine in patients taking midodrine.
AB  - Plasma metanephrines have become the biochemical test of choice for suspected
      phaeochromocytomas and paragangliomas in many institutions. We encountered two
      separate cases of significantly elevated plasma metanephrines in patients taking
      midodrine, a sympathomimetic drug used in the treatment of severe postural
      hypotension, in the absence of a diagnosis of phaeochromocytomas and
      paragangliomas. Upon stopping midodrine treatment, plasma metanephrine
      concentrations returned to normal in both patients. To explore the hypothesis
      that midodrine or its metabolite desglymidodrine might interfere with the
      metanephrines assay, we tested the interaction of midodrine with metanephrine
      assays from two different centres. High-performance liquid chromatography tandem
      mass spectrometry on plasma samples and on methanolic extract of midodrine
      demonstrated co-elution of the metabolite desglymidodrine with metanephrine. We
      conclude that patients taking midodrine may have falsely elevated plasma
      metanephrine as a result of analytical interference, and clinicians need to be
      aware of this problem.

PMID- 29357679
TI  - Area Deprivation Index Predicts Readmission Risk at an Urban Teaching Hospital.
AB  - A growing body of evidence has shown that neighborhood characteristics have
      significant effects on quality metrics that evaluate health plans or health care
      providers. Using a data set of an urban teaching hospital patient discharges,
      this study aimed to determine whether a significant effect of neighborhood
      characteristics, measured by the Area Deprivation Index, could be observed on
      patients' readmission risk, independent of patient-level clinical and demographic
      factors. This study found that patients residing in more disadvantaged
      neighborhoods had significantly higher 30-day readmission risks compared to those
      living in less disadvantaged neighborhoods, even after accounting for individual
      level factors. Those who lived in the most extremely socioeconomically challenged
      neighborhoods were 70% more likely to be readmitted than their counterparts who
      lived in less disadvantaged neighborhoods. These findings suggest that
      neighborhood-level factors should be considered along with individual-level
      factors in future work on adjustment of quality metrics for social risk factors.

PMID- 29357681
TI  - Corrigendum.
AB  - Lavezzi, A. M., Ferrero, S., Roncati, L., Piscioli, F., Matturri, L. & Pusiol, T.
      (2017). Nicotinic receptor abnormalities in the cerebellar cortex of sudden
      unexplained fetal and infant death victims-possible correlation with maternal
      smoking. ASN Neuro, 9, 1-10. DOI: 10.1177/1759091417720582 In figure 4, one of
      the labels mentioned at the bottom of graph is incorrect. Instead of "BDNF-index
      classes", the label should be " nAChR-index". The correct figure is shown below.

PMID- 29357680
TI  - Switching Language Modes: Complementary Brain Patterns for Formulaic and
      Propositional Language.
AB  - Language has been modeled as a rule governed behavior for generating an unlimited
      number of novel utterances using phonological, syntactic, and lexical processes.
      This view of language as essentially propositional is expanding as a contributory
      role of formulaic expressions (e.g., you know, have a nice day, how are you?) is
      increasingly recognized. The basic features of the functional anatomy of this
      language system have been described by studies of brain damage: left
      lateralization for propositional language and greater right lateralization and
      basal ganglia involvement for formulaic expressions. Positron emission tomography
      (PET) studies of cerebral blood flow (CBF) have established a cortical
      subcortical pattern of brain activity predictive of syllable rate during
      phonological/lexical repetition. The same analytic approach was applied to
      analyzing brain images obtained during spontaneous monologues. Sixteen normal,
      right-handed, native English speakers underwent PET scanning during several
      language tasks. Speech rate for the repetition of phonological/lexical items was
      predicted by increased CBF in the left inferior frontal region and decreased CBF
      in the head of the right caudate nucleus, replicating previous results. A
      complementary cortical-subcortical pattern (CBF increased in the right inferior
      frontal region and decreased in the left caudate) was predictive of the use of
      speech formulas during monologue speech. The use of propositional language during
      the monologues was associated with strong left lateralization (increased CBF at
      the left inferior frontal region and decreased CBF at the right inferior frontal
      region). Normal communication involves the integration of two language modes,
      formulaic and novel, that have different neural substrates.

PMID- 29357683
TI  - Cerebellar involvement in migraine.
AB  - Background Although there is a great wealth of knowledge about the
      neurobiological processes underlying migraine and its accompanying symptoms, the
      mechanisms by which an attack starts remain elusive, and the disease remains
      undertreated. Although the vast majority of literature focuses on the involvement
      of the trigeminovascular systems and higher systems it innervates, such as
      thalamic and hypothalamic nuclei, several lines of evidence implicate the
      cerebellum in the pathophysiology of migraine. Aim In this review, we aim to
      summarize potential cerebellar involvement seen from different perspectives
      including the results from imaging studies, cerebellar connectivity to migraine
      related brain structures, comorbidity with disorders implying cerebellar
      dysfunction, similarities in triggers precipitating both such disorders, and
      migraine and cerebellar expression of migraine-related genes and neuropeptides.
      We aim to inspire an increase in interest for future research on the subject.
      Conclusion It is hoped that future studies can provide an answer as to how the
      cerebellum may be involved and whether treatment options specifically targeting
      the cerebellum could provide alleviation of this disorder.

PMID- 29357682
TI  - Age differences in sexual risk behaviors and related factors among people living
      with HIV in Guangxi, China.
AB  - Sexual risk behaviors by people living with HIV (PLHIV) can result in secondary
      HIV transmission and other health problems. Given the dearth of research on age
      differences in sexual behaviors among PLHIV, the objective of the study is to
      compare sexual risk behaviors and related factors among PLHIV by age groups. Data
      used in the current study were derived from a cross-sectional survey conducted
      from 2012 to 2013 in Guangxi, China. PLHIV were selected randomly from 12 sites
      with the largest number of HIV/AIDS cases. The 2,987 PLHIV completing the survey
      were included in the study. Participants were asked about key sociodemographic
      characteristics, health condition, same-sex behavior, and sexual risk behaviors
      (number of sex partners, condom use consistency, and change in condom use after
      HIV diagnosis). Univariate logistic regression analyses were conducted to
      evaluate associations of sexual risk behaviors with age and other factors. Those
      variables with a p-value of less than 0.2 were entered into multivariate logistic
      regression models. All statistical analyses were conducted using SAS 9.4.
      Differences in sexual risk behaviors across age groups were observed. Compared
      with their younger counterparts, who were >= 50 years of age were more likely to
      have multiple partners, use condoms inconsistently, and use condoms less than
      before HIV diagnosis. Moreover, lower education attainment, being in the lowest
      or highest category of income, having a sero-concordant or sero-unknown steady
      partner or no steady partner, and having contracted HIV from steady or
      casual/commercial partners, or through injection drug use appeared to be
      predictive of at least one of the sexual risk behaviors examined in the study.
      The findings call for HIV prevention interventions to be tailored to different
      age groups. The interventions that can help reduce unprotected sex among older
      PLHIV are urgently needed.

PMID- 29357684
TI  - The True Ablation Effect of Holmium YAG Laser on Soft Tissue.
AB  - PURPOSE: The holmium YAG (Ho:YAG) laser penetration depth (PD) of 0.4 mm has been
      widely described. Nonetheless, in physics, this concept refers to the tissue
      thickness at which 90% of the energy has been absorbed and not to the incision
      depth (ID) that the laser can achieve in tissue. The aim of this study is to
      evaluate the ablation efficiency of Ho:YAG laser on soft tissue. MATERIALS AND
      METHODS: With an automated robotic arm, systematic fissures were performed on
      flat veal kidney specimens. Broad setting spectrums from 2.5 to 80 W, short and
      long pulse, were tested with 272 and 365 MUm laser fibers. Experiments were
      repeated three times. Two pathologists in a blinded manner measured the width,
      depth, and coagulation area with electronic microscopy. RESULTS: The overall mean
      ID was 2 mm (0.25-4.39) and the mean width was 1 mm (0.3-3.1). The mean
      coagulation thickness was 0.48 mm (0.25-1.73). The higher the frequency and
      energy, the deeper and wider was the incision p < 0.001. No differences were
      observed regarding the fiber diameter. The pulse length did not affect the ID,
      although the mean width was greater with short pulse p = 0.04. The outer mean
      coagulation was increased by increasing energy but not by increasing frequency p
      > 0.119. CONCLUSIONS: The overall mean ID was significantly higher than the
      theoretical 0.4 mm PD described for Ho:YAG laser. The energy, frequency, and
      pulse length had individual effects regarding ID, incision width, and
      coagulation. The ID should be specified in accordance with the laser's power
      output and should not be confused with the physics of PD concept.

PMID- 29357686
TI  - Thulium Laser Treatment of Upper Urinary Tract Carcinoma: A Multi-Institutional
      Analysis of Surgical and Oncological Outcomes.
AB  - INTRODUCTION: To evaluate the efficacy and safety of ureteroscopic thulium laser
      (TL) treatment of upper urinary tract carcinoma (UTUC). MATERIALS AND METHODS:
      Forty-two consecutive patients underwent conservative TL treatment for UTUC at
      two referral institutions. All patients underwent preliminary biopsy and then
      laser vaporization. A 272 MUm and 365 MUm laser fibers were used with a flexible
      and semirigid scope, respectively. Ablation was carried out with a 10 to 20 W
      power. RESULTS: Mean age at surgery was 68 years (SD 10.7). Mean tumor size was
      14.3 mm (range 2-30 mm). Preliminary biopsy revealed the presence of low-grade
      disease in 29 (69.1%) patients, high-grade disease in 4 (9.5%) and 1 carcinoma in
      situ 1 (2.4%), whereas it was not conclusive in 8 (19%) cases. Final stage was
      pTa and pTis in 41 (97.6%) and 1 (2.4%) patients, respectively. Thirty eight
      percent (16) experienced Clavien-Dindo grade I complication, 47.6% (20) grade II,
      and 2.4% (1) grade III. Five (12%) patients underwent a second-look procedure due
      to residual disease. Eight (19%) patients experienced clinical recurrence. The
      median estimated recurrence-free survival was 44 months (SE 3.68). Four patients
      (9.5%) underwent a nephroureterectomy. Final pathological stage was pTis, pT3
      high grade, pTa low grade, and pT0. Median follow-up was 26.3 months (range 2-54
      months), and no progression or upstaging of disease occurred. CONCLUSIONS: TL
      management of UTUC is a safe and efficacious conservative treatment. Our
      experience shows optimal vaporization and hemostatic control in the absence of
      major complications.

PMID- 29357685
TI  - Case-Based Learning in Dermatology.
AB  - IMPORTANCE: The instruction of dermatology can be challenging due to its large
      scope, heavy clinical nature, and limited curriculum space. Case-based learning
      (CBL) is an emerging education paradigm and has no current literature on its use
      in dermatology. OBJECTIVES: Assess CBL in undergraduate dermatology medical
      education. METHODS: Case-based learning was implemented in the preclerkship
      dermatology curriculum at the University of Toronto to 3 student cohorts
      (totaling 710 students and 93 tutors) between May 2016 and April 2017. We
      analyzed assignment performance, pre- and post-CBL knowledge test scores, and
      experience surveys on students and tutors. Surveys were evaluated using aggregate
      descriptive statistics for quantitative data and thematic data analysis for
      qualitative data. All assessments were anonymous and voluntary. RESULTS: We
      received strong positive feedback on the CBL experience, with no score less than
      3.8 on a 5-point scale (where 5 indicated strongly agree with a positively
      phrased question). Thematic data analysis revealed several key themes, including
      positive comments for a specialist tutor, the use of visual media, and the "mini
      cases" style of CBL, while challenges included a lack of motivation. Group
      assignments scored high, ranging from 88.9% to 99.3%. Tracked pre- and post-CBL
      knowledge test scores showed a 32% (from 42% to 74%) increase in scores after the
      CBL experience. Conclusion and Relevance: CBL in dermatology medical education
      was well received by students and tutors, with high scores in content evaluation
      and knowledge assessment. Future studies should examine optimal delivery methods
      and its long-term effects on knowledge retention.

PMID- 29357687
TI  - In-stent restenosis: surgical and histopathological perspective.
AB  - Background In-stent restenosis has been recognized as a distinct clinical entity
      that warrants a repeat procedure either in the form of percutaneous
      reintervention or coronary artery bypass grafting. Multivessel grafting with
      endarterectomy and explantation of the stent is rarely performed, with few cases
      reported in the literature. We aim to study the pathomorphology of the stent
      vascular interface in coronary vessels undergoing in-stent restenosis. Methods
      Over a period of 3 years, 3 patients who had undergone angioplasty for diffuse
      coronary artery disease developed in-stent restenosis and were advised coronary
      artery bypass. The mean age was 53 years, the average time from the previous
      intervention was 77 months. Coronary endarterectomy with stent removal and
      concomitant multivessel coronary artery bypass was performed. Results Histology
      showed significant proliferation of the well-endothelialized intima as the reason
      for in-stent restenosis. There were no signs of local thrombus formation or
      increased inflammatory activity in any of the specimens. After coronary artery
      bypass, all patients were asymptomatic at a mean follow-up of 32 months.
      Conclusion Coronary endarterectomy with stent explantation and multivessel
      coronary artery bypass is a procedure that requires attention because the need is
      increasing due to the rise in the number of angioplasties. The complexity of this
      procedure increases to the extent that the adventitia is involved during stent
      explantation.

PMID- 29357688
TI  - Congenital mitral regurgitation with Down syndrome.
AB  - A 19-year-old man with Down syndrome had congenital mitral regurgitation. He had
      slight mental retardation and difficulty in performing independent oral drug
      administration. We planned mitral valve plasty to avoid postoperative
      anticoagulant therapy. The mitral valve lesions were complicated. A prolapsed
      anterior mitral leaflet, shortened posterior leaflet, abnormal cleft, abnormal
      papillary muscle, and enlarged annulus were observed. Successful mitral valve
      plasty was performed using several techniques. The postoperative course was
      uneventful, and no significant mitral regurgitation was found.

PMID- 29357690
TI  - Corrigendum.

PMID- 29357689
TI  - A qualitative exploration of the experiences of adoptive parents attending
      'Nurturing Attachments', a dyadic developmental psychotherapy informed group.
AB  - Children who are adopted have frequently experienced a range of aversive
      experience which impact on their ability to form secure attachments. Dyadic
      Developmental Psychotherapy (DDP) is an intervention designed to develop and
      promote secure attachments with children who have experienced developmental
      trauma. Eight adoptive parents participated in semi-structured interviews
      regarding their experiences of attending the 'Nurturing Attachment' group
      informed by DDP. The transcripts of their interviews were explored using
      Interpretative Phenomenological Analysis. The analysis revealed five inter
      connected superordinate themes which were as follows: A supportive group, A shift
      in perspective, 'Turning trauma into secure attachment', 'Am I doing it right?'
      and Continuing the adoption journey. Themes are considered in relation to the
      theoretical underpinnings and practice of DDP. Some further implications for
      clinical and research practice are also discussed.

PMID- 29357691
TI  - Micro- and nano-capsulated fungal pectinase with outstanding capabilities of
      eliminating turbidity in freshly produced juice.
AB  - The present study aimed to compare the pectinase forms produced from Trichoderma
      viride-free, micro-capsule, and nano-capsule-in sodium alginate to analyze the
      pectin that causes the turbidity of orange juice. This was performed along with
      an estimation of viscosity, residual of pectin, and turbidity. The extracted and
      purified enzyme was 24.35-fold better than that of the crude enzyme. After
      application of free one, it loses most of the activity on low degrees of acidity
      and remains constant on the temperatures of pasteurization. Therefore, the tested
      enzyme was encapsulated by two different ways using the same polymer. The
      morphology of the three pectinase forms was obtained by transmission electron
      microscopy, and the micrographs clearly showed the pores on the surface of sodium
      alginate matrix after encapsulation. The size of the wall (sodium alginate)
      ranged from 3.24 to 3.76 um diameter but was 3.15 um for core of enzyme. Micro
      capsuled and nano-capsuled pectinase can be used in the hydrolysis of pectic
      substances in orange juice with natural ways and maintaining the quality of final
      product. Consequently, the cost of juice clarifying can be reduced due to reusing
      the enzyme several times.

PMID- 29357692
TI  - Effect of application of edible coating and packaging on the quality of pansies (
      Viola * wittrockiana) of different colors and sizes.
AB  - The effects of alginate edible coating on the quality of pansies (visual
      appearance, weight loss, water activity, color, and dimensions change) were
      studied during refrigerated storage (4 C). The role of pansies' color and size,
      as well as packaging, was also studied. Alginate treatments resulted in a
      beneficial effect on the visual appearance of pansies under refrigerated storage
      when compared to the uncoated, delaying their degradation from 3-4 days up to 14
      days, depending on the pansies' color, probably derived from their different
      petal thicknesses (83 to 183 um for yellow and red pansies). The unpackaged
      coated pansies had different behaviors during storage, associated with their
      dimensions (the larger coated pansies maintained good visual appearance during
      longer storage times than the smaller ones). However, the packaged pansies
      treated with edible coating showed to have lower weight loss and shrinkage than
      the unpackaged, irrespective of the color and size, with physical stability up to
      14 days. In summary, the cumulative use of alginate coating with packaging under
      refrigerated storage may contribute to extend pansies' shelf life.

PMID- 29357695
TI  - The Art of Health Promotion: Linking research to practice.

PMID- 29357693
TI  - Parental Characteristics and Reasons Associated With Purchasing Kids' Meals for
      Their Children.
AB  - PURPOSE: Characteristics of parents who purchased kids' meals, reasons for the
      purchase, and desire for healthy options were examined. DESIGN: Quantitative,
      cross-sectional study. SETTING: National. PARTICIPANTS: The SummerStyles survey
      data of 1147 parents (>=18 years). MEASURES: Self-reported outcome variables were
      purchase of kids' meals (yes/no), reasons for the purchase (13 choices), and
      desire for healthy options (yes/no). ANALYSIS: We used multivariable logistic
      regression to estimate odds ratios (ORs) for purchasing kids' meals based on
      parental sociodemographic and behavioral characteristics. RESULTS: Over half
      (51%) of parents reported purchasing kids' meals in the past month. The adjusted
      OR of purchasing kids' meals were significantly higher among younger parents (OR
      = 3.44 vs >=50 years) and among parents who consumed sugar-sweetened beverages
      (SSBs) daily (OR = 2.70 vs none). No differences were found for race/ethnicity,
      income, and education. Parents who purchased kids' meals reported that the top 3
      reasons for purchase were (1) because their children asked for kids' meals, (2)
      habit, and (3) offering of healthier sides such as fruits or fruit cups. Thirty
      seven percent of parents who did not purchase kids' meals expressed willingness
      to purchase kids' meals if healthy options were available; this willingness was
      highest among younger parents (47%; P < .05). CONCLUSIONS: Kids' meal purchases
      were somewhat common. Our findings on characteristics of parents who frequently
      bought kids' meals (ie, younger parents and SSB consumers), common reasons for
      purchasing kids' meals, and willingness to buy healthier kids' meal can be used
      to inform intervention efforts to improve quality of kids' meals.

PMID- 29357696
TI  - The Parity in Health Promotion Issue.
AB  - Health promotion is complex even when issues of justice and equity are not
      considered. The dynamic influences of culture, environments, education and
      upbringing all collude to make promoting fitness, happiness or healthy eating as
      exciting and unpredictable as a Mars mission. Add the goal of equivalence of
      benefit for all to this mix, and the launch pad is ever more volatile. To solve
      for parity we will need to struggle between two of the most time-honored of moral
      principles. Consequentialism holds that, as Star Trek's Dr. Spock said with his
      dying breath in his final episode, "the needs of the many are more important than
      the needs of a few." Categorical reasoning is a belief system where some things
      are morally righteous no matter the context. Choosing the right principles will
      require that we better leverage "citizen scientists" because one of the surest
      ways to satisfy a community's context is to recruit community partners.

PMID- 29357697
TI  - Living with a disability: a qualitative study of associations between social
      relations, social participation and quality of life.
AB  - PURPOSE: We explored which shared aspects of social relations were considered
      important to the quality of life of persons between the ages of 10 and 40 years
      living with a disability. We examined how social relations were experienced as
      affecting quality of life and social participation. MATERIALS AND METHODS:
      Fifteen focus groups involving 48 persons with disabilities were conducted using
      photo elicitation, preference ranking and props. Focus group interviews were
      supplemented with seven individual interviews with individuals unable to
      participate in focus groups. All focus group interviews and individual interviews
      were audiotaped, transcribed, and thematic data analysis was conducted. RESULTS:
      We identified caregiving, dependency, and understanding as essential for quality
      of life. Acceptance from society, discrimination and prejudice, and the ability
      to participate in society were also highlighted as affecting quality of life. The
      use of social tactics to avoid confrontation with certain aspects of their
      disability was common among participants. CONCLUSIONS: Across disabilities,
      caregiving, dependency, understanding and acceptance, and discrimination and
      prejudice were all important aspects for the quality of life of the individuals.
      Social relations were closely related to social participation, and the latter
      affected the quality of life of the participants. Social tactics were used to
      navigate social relations. Implications for rehabilitation We suggest to
      formalize the concept of social tactics and use it in patient education to
      enhance quality of life in individuals living with disabilities. People may
      accept and learn to cope with the impact of their disability, but how they
      maintain their social participation and social relations also impact on their
      quality of life. In their assessment, professionals working with individuals with
      disabilities should, therefore, give more priority to analyze the impact of
      social relations. When intervening, an effort to establish and maintain social
      relations should be considered along with psychological help, allocation of aids
      and economical support aiming to enhance quality of life and social participation
      among individuals with disabilities. When evaluating efforts to improve quality
      of life, it is important to investigate whether the intervention has improved the
      social relations.

PMID- 29357698
TI  - Chronotype is associated with psychological well-being depending on the
      composition of the study sample.
AB  - Past studies examining the effect of chronotype and social jetlag on
      psychological well-being have been inconsistent so far. Here, we recruited
      participants from the general population and enquired about their natural
      sleeping behavior, sleep quality, depressive symptoms, and perceived stress.
      Partial correlations were computed between sleep variables and indicators of
      psychological well-being, controlling for age and sex. Less sleep during work
      days was found a good indicator for impairments in psychological well-being. In
      exploratory follow-up analyses, the same correlations were calculated within
      groups of early, intermediate, and late chronotype. We observed that the
      composition of the sample in terms of chronotype influenced whether associations
      between sleep variables and psychological well-being could be observed, a finding
      that is advised to be taken into account in future studies.

PMID- 29357700
TI  - YKL-40 in patients with end-stage renal disease receiving haemodialysis.
AB  - PURPOSE: This study aimed to determine serum YKL-40 in patients with end-stage
      renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value
      of serum YKL-40. METHODS: Patients >18 years on maintenance HD were included.
      Serum YKL-40 was measured using ELISA before and after a single HD treatment.
      RESULTS: A total of 306 patients were included. Median serum YKL-40 concentration
      was 238 ugL-1 (IQR: 193-291 ugL-1) before HD treatment and 198 ugL-1 (IQR: 147
      258 ugL-1) after HD treatment, which corresponded to age-corrected 93th
      percentile in healthy subjects. All-cause mortality after 2.8 years was 35.9%.
      Patients with serum YKL-40 in the highest quartile compared with the lowest
      quartile had a univariate HR of 4.0 (95% CI: 2.2-7.3, p < 0.001) for all-cause
      mortality which decreased to 2.4 (95% CI: 1.1-4.5, p = 0.01) in multivariate
      analysis. Time-dependent receiver operating characteristic curves showed that
      serum YKL-40 after HD treatment had significant higher area under the curves from
      90 d (p = 0.004) and throughout the rest of the follow-up period when compared to
      serum YKL-40 before HD treatment. CONCLUSION: YKL-40 was highly elevated in
      patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations
      approximately one-sixth. YKL-40 measured after dialysis was independently
      associated with mortality in HD patients.

PMID- 29357701
TI  - Comparison of Exposure in the Kaplan Versus the Kocher Approach in the Treatment
      of Radial Head Fractures.
AB  - BACKGROUND: The aim of this study was to compare the complete visible surface
      area of the radial head, neck, and coronoid in the Kaplan and Kocher approaches
      to the lateral elbow. The hypothesis was that the Kaplan approach would afford
      greater visibility due to the differential anatomy of the intermuscular planes.
      METHODS: Ten cadavers were dissected with the Kaplan and Kocher approaches, and
      the visible surface area was measured in situ using a 3-dimensional digitizer.
      Six measurements were taken for each approach by 2 surgeons, and the mean of
      these measurements were analyzed. RESULTS: The mean surface area visible with the
      lateral collateral ligament (LCL) preserved in the Kaplan approach was 616.6 mm2
      in comparison with the surface area of 136.2 mm2 visible in the Kocher approach
      when the LCL was preserved. Using a 2-way analysis of variance, the difference
      between these 2 approaches was statistically significant. When the LCL complex
      was incised in the Kocher approach, the average visible surface area of the
      Kocher approach was 456.1 mm2 and was statistically less than the Kaplan
      approach. The average surface area of the coronoid visible using a proximally
      extended Kaplan approach was 197.8 mm2. CONCLUSIONS: The Kaplan approach affords
      significantly greater visible surface area of the proximal radius than the Kocher
      approach.

PMID- 29357699
TI  - Psychopathological dimensions in subjects with hereditary ATTR V30M amyloidosis
      and their relation with life events due to the disease.
AB  - BACKGROUND: Chronic physical illness has been associated with emotional distress.
      Chronic diseases may change usual family patterns with economic, social and
      family losses. Hereditary ATTR V30M amyloidosis is a rare, fatal inherited
      systemic amyloidosis, with chronic evolution and beginning in adulthood. AIMS AND
      METHODS: To evaluate psychopathological dimensions and how they correlated with
      disease-related life events, 209 symptomatic and asymptomatic carriers,
      participated in the study. Sociodemographic and Family and Personal History
      Disease questionnaires and brief symptom inventory (BSI) were applied. RESULTS:
      BSI indices, global severity index (GSI), positive symptom index (PSI) and
      positive symptom total (PST) scored higher than general population. Independent
      predictors for GSI >0.83 were female sex (OR = 3.46, p = .005) and being
      symptomatic carriers (OR = 3.03, p = .039). Independent predictors of a PST
      >26.99 were female sex (OR = 3.74, p = .012) symptomatic carrier (OR = 5.32, p =
      .025), age between 15 and 24 years at affected parent's death (OR = 5.26, p =
      .04). Independent predictors of a PSI >1.56 were being asymptomatic carrier (OR =
      6.3, p = .036); to have children (OR = 3.19, p = .043) and have <=14 years at
      parent's disease onset (OR = 6.39, p = .05). CONCLUSIONS: Results point to an
      important vulnerability of this population for psychological distress and
      psychiatric disease. Early life events related to disease, being sick and sex are
      associated with psychopathological distress.

PMID- 29357702
TI  - The Vascularity and Osteogenesis of a Vascularized Flap for the Treatment of
      Scaphoid Nonunion: The Pedicle Volar Distal Radial Periosteal Flap.
AB  - BACKGROUND: Vascularized periosteal flaps from the distal radius have been
      previously proposed. The purpose of this study was to investigate the vascularity
      and osteogenic potential of a vascularized volar distal radial periosteal flap
      for the treatment of scaphoid nonunion. METHODS: In 5 fresh frozen cadavers, a
      rectangular periosteal flap was elevated from the distal radius with the pedicle
      just proximal to the watershed line. Latex dye was injected into the radial
      artery proximally and the vascularity of the flap characterized by microscopic
      evaluation. Patients with scaphoid nonunion were then treated with open
      reduction, internal fixation, and distal radius cancellous bone graft. Two groups
      of patients with midwaist nonunion scaphoid were then evaluated. The first group
      received the vascularized periosteal flap and the second group received a
      nonvascularized periosteal flap. A third group of proximal pole nonunions also
      received the vascularized flap. RESULTS: Cadaveric dissections revealed that all
      of the injected flaps demonstrated vascularity to the distal edge of the flap.
      Vascularized flaps formed visible bone on imaging in 55% of cases. None of the
      nonvascularized flaps formed visible bone. In group 1, 12/12 midwaist nonunions
      united. In group 2, union was achieved in 6/6 of patients who completed the
      follow-up. In group 3, 6/7 proximal pole fractures united. CONCLUSIONS:
      Previously proposed vascularized periosteal flaps from the distal radius appear
      to possess notable osteogenic potential that may be of interest to surgeons
      treating scaphoid nonunion.

PMID- 29357703
TI  - Progress in bipolar disorder drug design toward the development of novel
      therapeutic targets: a clinician's perspective.
AB  - INTRODUCTION: Bipolar disorder (BD) is a considerable burden to the affected
      individual. The need for novel drug targets and improved drug design (DD) in BD
      is therefore clear. Areas covered: The following article provides a brief,
      narrative, clinician-oriented overview of the most promising novel
      pharmacological targets for BD along with a concise overview regarding the
      general DD process and the unmet needs relevant to BD. Expert opinion: A number
      of novel potential drug targets have been investigated. With the notable
      exception of the kynurenine pathway, available evidence is too scarce to
      highlight a definitive roadmap for forthcoming DD in BD. BD itself may present
      with different facets, as it is a polymorphic clinical spectrum. Therefore,
      promoting clinical-case stratification should be based on precision medicine,
      rather than on novel biological targets. Furthermore, the full release of raw
      study data to the scientific community and the development of uniform clinical
      trial standards (including more realistic outcomes) should be promoted to
      facilitate the DD process in BD.

PMID- 29357704
TI  - Correction to: Rakugi et al., A phase III, open-label, multicenter study to
      evaluate the safety and efficacy of long-term triple combination therapy with
      azilsartan, amlodipine, and hydrochlorothiazide in patients with essential
      hypertension.

PMID- 29357705
TI  - A new bis-gamma-pyrone polypropionate from a marine pulmonate mollusc Onchidium
      struma.
AB  - A new bis-gamma-pyrone polypropionate compound onchidione II (1), together with
      three known compounds, was isolated from a marine pulmonate mollusc Onchidium
      struma, collected at Hainan Island of China. The structure of new compound was
      determined by extensive spectroscopic analyses including IR, 1D and 2D NMR
      techniques, and chemical methods. Compounds 1-4 were evaluated for their
      cytotoxicity against human tumor cell lines HepG-2, A549, and MCF-2. The results
      showed that compounds 1 and 2 were moderate cytotoxic against HepG-2, A549, and
      MCF-2 cell lines, with IC50 values from 13.2 to 22.4 MUM.

PMID- 29357706
TI  - Cognitive, emotional, and behavioral considerations for chronic pain management
      in the Ehlers-Danlos syndrome hypermobility-type: a narrative review.
AB  - BACKGROUND: Ehlers-Danlos syndrome (EDS) hypermobility-type is the most common
      hereditary disorder of the connective tissue. The tissue fragility characteristic
      of this condition leads to multi-systemic symptoms in which pain, often severe,
      chronic, and disabling, is the most experienced. Clinical observations suggest
      that the complex patient with EDS hypermobility-type is refractory toward several
      biomedical and physical approaches. In this context and in accordance with the
      contemporary conceptualization of pain (biopsychosocial perspective), the
      identification of psychological aspects involved in the pain experience can be
      useful to improve interventions for this under-recognized pathology. PURPOSE:
      Review of the literature on joint hypermobility and EDS hypermobility-type
      concerning psychological factors linked to pain chronicity and disability.
      METHODS: A comprehensive search was performed using scientific online databases
      and references lists, encompassing publications reporting quantitative and
      qualitative research as well as unpublished literature. RESULTS: Despite scarce
      research, psychological factors associated with EDS hypermobility-type that
      potentially affect pain chronicity and disability were identified. These are
      cognitive problems and attention to body sensations, negative emotions, and
      unhealthy patterns of activity (hypo/hyperactivity). CONCLUSIONS: As in other
      chronic pain conditions, these aspects should be more explored in EDS
      hypermobility-type, and integrated into chronic pain prevention and management
      programs. Implications for Rehabilitation Clinicians should be aware that joint
      hypermobility may be associated with other health problems, and in its presence
      suspect a heritable disorder of connective tissue such as the Ehlers-Danlos
      syndrome (EDS) hypermobility-type, in which chronic pain is one of the most
      frequent and invalidating symptoms. It is necessary to explore the psychosocial
      functioning of patients as part of the overall chronic pain management in the EDS
      hypermobility-type, especially when they do not respond to biomedical approaches
      as psychological factors may be operating against rehabilitation. Further
      research on the psychological factors linked to pain chronicity and disability in
      the EDS hypermobility-type is needed.

PMID- 29357707
TI  - Use of polymers for taste-masking pediatric drug products.
AB  - Many drugs are bitter and overcoming this bitter taste is a major barrier in
      developing a successful product, especially for pediatric patients. Approaches to
      mask taste include changing taste perception, creating a physical barrier to
      separate the drug from interacting with taste buds, and changing drug solubility.
      This review is focused on polymers and the different ways these materials are
      used to achieve taste masking. Attention is given to systems that are easily
      swallowed, as swallowability is another concern in developing palatable products
      for pediatrics. Variables that should be considered when selecting a taste
      masking approach are also presented.

PMID- 29357708
TI  - Impact of systolic pulmonary artery pressure on all-cause mortality in elderly
      cardiac patients.
AB  - OBJECTIVE: Elevated systolic pulmonary artery pressure (sPAP) is common among
      elderly patients with cardiac and pulmonary diseases. The lowest level of sPAP
      associated with increased mortality rate in octogenarians with cardiac diseases
      is however not sufficiently studied. Therefore, the present study aimed to
      identify the lowest level of sPAP associated with increased 5-year all-cause
      mortality in this patient group. DESIGN: Of 538 octogenarians presented at the
      three Sahlgrenska University Hospitals (Sahlgrenska, Ostra and Molndal) with
      either congestive heart failure (CHF) or acute coronary syndrome (ACS), only 302
      patients who had undergone echocardiography with data on sPAP were included in
      the present study. In order to identify the lowest level of sPAP associated with
      increased mortality rate, Cox proportional-hazard regression multivariable models
      were built for sPAP levels as low as 30 mmHg and upward with 5 mmHg intervals.
      RESULTS: sPAP >35 mmHg was identified as the lowest level associated with
      increased 5-year all-cause mortality (HR = 1.7, 95% of CI = 1.1-2.6 and p =
      .013). Every increase of 5 mmHg in sPAP was associated with a 10% increased
      relative risk for all-cause mortality. CONCLUSIONS: In octogenarians with cardiac
      diseases the lowest level of sPAP associated with increased all-cause mortality
      was >35 mmHg and the mortality rate increased with increasing sPAP.

PMID- 29357709
TI  - Blood-Brain Barrier Disruption, Sodium Fluorescein, And Fluorescence-Guided
      Surgery Of Gliomas.
AB  - PURPOSE: Sodium fluorescein (SF) is an ideal dye for intraoperative guided
      resection of high-grade gliomas (HGGs). However, it is not well understood
      whether the SF-guided technique is suitable for different grades of gliomas, and
      the correlation between fluorescence and pathology is also not yet clear.
      MATERIALS AND METHODS: In this study, we investigated 28 patients, including 23
      patients with HGG and 5 patients with low-grade glioma (LGG). All patients were
      treated using the SF-guided technique on a Pentero 900 microscope (Carl Zeiss,
      Oberkochen, Germany). Claudin-5 immunohistochemical (IHC) staining for the
      tumours and peritumour tissues was analyzed. RESULTS: Intraoperative yellow
      fluorescence was noted in all the HGGs but not in the LGGs. Claudin-5 expression
      in the blood brain barrier endothelial cells was downregulated and disconnected
      in the HGGs (p < 0.05), but had no difference or slightly decreased in the LGGs
      (p > 0.05). CONCLUSIONS: The SF-guided technique is suitable for HGG surgery but
      not for LGG surgery. Downregulation of claudin-5 expression may contribute to the
      presence of yellow fluorescence in the glioma in SF-guided surgery.

PMID- 29357710
TI  - Lasting improvements in left spatial neglect following a protocol combining neck
      muscle vibration and voluntary arm movements: a case-study.
AB  - PURPOSE: Beyond promising experimental results of sensory passive stimulations in
      spatial cognition disorders, some questions still remain regarding interests of
      these stimulations during the daily activities in neglect. The aim of this case
      study was to evaluate the effects of a protocol combining left neck-muscle
      vibration with daily simple movements, like arm pointing movements, on perceptivo
      locomotor deficits in a left spatial neglect patient. MATERIALS AND METHODS: Two
      neuropsychological tests, one subjective straight-ahead pointing (SSA) test and
      one wheelchair navigation test were carried out before the combination protocol,
      immediately after, 1 h later, and 24 h later. RESULTS: The results showed a
      reduction of neglect spatial bias following the protocol lasted at least 24 h in
      all the tests (except for the SSA test due to the unavailability of the pointing
      device). CONCLUSIONS: The range of improvements in the symptoms of spatial
      neglect suggests that this therapeutic intervention based on the combining neck
      muscle vibration to voluntary arm movements could be a useful treatment for this
      condition. One of future investigation axes should be the development of a
      vibratory tool in order to facilitate the combining this proprioceptive
      stimulation to daily activities. Implications for rehabilitation Spatial neglect
      is a perplexing neuropsychological syndrome, affecting different domains of
      spatial cognition and impacting also the functional domain. The treatments based
      on neck-muscle vibration are simple to use, non-invasive and requires none active
      participation of patient. A therapeutic intervention based on the combining left
      neck-muscle vibration and voluntary arm movements in a left-spatial-neglect show
      a lasting reduction of symptoms especially in daily activities. The combination
      of treatments based on the Bottom-Up approach opens innovative perspectives in
      rehabilitation.

PMID- 29357711
TI  - lncRNA profiling in NCI-H292 cells after stimulation with Dermatophagoides
      farinae extracts.
AB  - Airway epithelium cells are the first line of defense against airborne allergens.
      When cultured, epithelial cells can be exposed to various allergens, providing an
      ideal model to investigate allergic disorders. This study sought to characterize
      the profile of long noncoding (lnc) RNAs, which can regulate gene expression and
      exert functions in diverse cellular processes, in airway epithelial cells exposed
      to house dust mite allergens. NCI-H292 cells were exposed to house dust mite
      extract for 24 h. RNA expression was profiled in exposed and unexposed cells.
      There were 270 lncRNAs that were differentially expressed (fold change >= 2, P <
      0.05) in NCI-H292 cells after stimulation with Dermatophagoides farinae (house
      dust mite) extracts. Furthermore, 119 lncRNAs and 22 messenger RNAs were co
      expressed. Gene Ontology analysis showed that these under-regulated and up
      regulated lncRNAs were associated with biological process, cellular component,
      and molecular function. After bioinformatic analysis of significantly regulated
      signaling pathways, we found these lncRNAs may target 16 gene pathways, including
      glycolysis, axon guidance, ErbB signaling, and mitogen-activated protein kinases
      (MAPK) signaling. The identification of differentially regulated lncRNAs in NCI
      H292 cells after stimulation with Dermatophagoides farinae extracts, as well as
      their target gene pathways, can provide insight to the etiology and pathogenesis
      of allergy.

PMID- 29357712
TI  - Recent Progress on Genetic Diagnosis and Therapy for beta-Thalassemia in China
      and Around the World.
AB  - Thalassemia is a recessive monogenic hematological disease associated with
      reduced amounts of functional hemoglobin caused by mutations/deletions in at
      least one of the globin genes. This disease has attracted significant attention
      throughout the years in terms of genetic diagnosis and developments in gene and
      cell therapy. Here, recent progress is reviewed in the genetic diagnosis and
      development of therapeutics for thalassemia, particularly beta-thalassemia, in
      China and around the world.

PMID- 29357713
TI  - The budget impact of brodalumab for the treatment of moderate-to-severe plaque
      psoriasis on US commercial health plans.
AB  - INTRODUCTION: Brodalumab is a new biologic approved by the US Food and Drug
      Administration in 2017 for the treatment of moderate-severe psoriasis. This study
      evaluated the impact of the introduction of brodalumab on the pharmacy budget on
      US commercial health plans. METHODS: An Excel-based health economic decision
      analytic model with a US health plan perspective was developed. The model
      incorporated published moderate-to-severe psoriasis prevalence data; market
      shares of common biologic drugs, including adalimumab, ustekinumab, secukinumab,
      ixekizumab, and etanercept, used for the treatment of moderate-severe psoriasis;
      2017-year Wholesale Acquisition Costs for the biologic drugs; drug dispensing
      fee; patient co-pay; and drug contracting discount. Total annual health plan
      costs for the biologic drugs were estimated. Scenarios with different proportions
      of patients treated with brodalumab were compared to a control scenario when no
      brodalumab was used. RESULTS: In a hypothetical commercial health plan covering
      two million members, 7,038 moderate-to-severe psoriasis patients were estimated
      to be eligible for treatment with brodalumab. Prior to brodalumab approval, the
      proportions of patients treated by other biologics were estimated at 50.8% for
      adalimumab, 13.5% for ustekinumab, 14.1% for secukinumab, 4.4% for ixekizumab,
      and 17.2% for etanercept. With a 20% drug price discount applied to all
      biologics, the annual health plan costs for brodalumab, adalimumab, ustekinumab,
      secukinumab, ixekizumab, and etanercept were estimated at $37,224, $49,166,
      $55,084, $56,061, $64,396, and $57,170, respectively. When no brodalumab is used,
      the total annual pharmacy budget for the biologics used among these patients was
      estimated at $414,362,647. Among scenarios where the proportions of brodalumab
      usage were 3%, 8%, 16%, and 30%, the total annual pharmacy cost was estimated to
      be reduced by $3,698,129, $9,861,677, $19,723,355, and $36,981,290, respectively.
      CONCLUSION: Based on the economic model, brodalumab has the potential to
      substantially reduce pharmacy expenditures for the treatment of patients with
      moderate-to-severe plaque psoriasis in the US.

PMID- 29357714
TI  - Risks and benefits of medications for panic disorder: a comparison of SSRIs and
      benzodiazepines.
AB  - INTRODUCTION: Panic disorder (PD) is a prevalent and disabling anxiety disorder
      that can be treated effectively. Selective serotonin reuptake inhibitors (SSRIs)
      and benzodiazepines are among the most frequently prescribed drugs for PD. In
      this article, the authors review the current evidence on efficacy, adverse
      events, and limitations of these two treatment options. Areas covered:
      MEDLINE/Pubmed and Web of Science databases were searched for open or placebo
      controlled trials on SSRIs and/or benzodiazepines in PD treatment. Expert
      opinion: The literature search yielded 4,957 articles related to the theme. Of
      these, 24 articles were included in this review. Despite their usefulness in PD,
      SSRIs are associated with a delay of several weeks in onset of therapeutic effect
      and have the potential to exacerbate anxiety and panic early in the treatment
      course. Benzodiazepines present rapid onset of action, but can cause tolerance
      and dependence. Despite strong evidence of the effectiveness of SSRIs and
      benzodiazepines in the treatment of PD, few trials have performed head-to-head
      comparisons of these two drug classes. Future studies on the pharmacological
      treatment of PD should make direct comparisons of risks, benefits, and
      limitations of each group. This could help improve the evidence-based
      pharmacotherapy of PD.

PMID- 29357715
TI  - Economic burden of varicella in children 1-12 years of age in Argentina, 2009
      2014.
AB  - BACKGROUND: In Argentina, varicella vaccination was included in the national
      schedule for mandatory immunizations in 2015. The vaccine has been shown to
      substantially reduce the morbidity and mortality associated with the virus. The
      purpose of this study was to evaluate the clinical and economic burden associated
      with varicella in Argentina prior to vaccine introduction. METHODS: This was a
      multi-center, retrospective chart review study among patients aged 1-12 years
      with a primary varicella diagnosis in 2009-2014 in Argentina. Healthcare resource
      utilization (HCRU) associated with varicella and its complications, unit costs,
      and work loss were used to estimate direct and indirect costs. All costs are
      presented in 2015 United States dollars (USD). RESULTS: One hundred and fifty
      children with varicella were included (75 outpatients, 75 inpatients), with a
      mean age of 3.8 (SD = 2.4) and 2.9 (SD = 2.2) years, respectively. One or more
      complications were experienced by 28.0% of outpatients and 98.7% of inpatients,
      the most common being skin and soft tissue infections, pneumonia, sepsis,
      cerebellitis, and febrile seizure. HCRU estimates included use of over-the
      counter (OTC) medications (58.7% outpatients, 94.7% inpatients), prescription
      medications (26.7% outpatients, 77.3% inpatients), tests/procedures (13.3%
      outpatients, 70.7% inpatients), and consultation with allied health professionals
      (1.3% outpatients, 32.0% inpatients). The average duration of hospital stay was
      4.9 (95% CI = 4.2-5.7) days, and the average duration of ICU stay was 4.8 (95% CI
      = 1.6-14.1) days. The total combined direct and indirect cost per varicella case
      was 2947.7 USD (inpatients) and 322.7 USD (outpatients). The overall annual cost
      of varicella in Argentina for children aged <=14 years in 2015 was estimated at
      40,054,378.0 USD. CONCLUSION: The clinical burden of varicella in Argentina was
      associated with utilization of significant amounts of healthcare resources,
      resulting in substantial economic costs. These costs should be reduced with the
      recent implementation of routine vaccination of children.

PMID- 29357716
TI  - The design briefing process matters: a case study on telehealthcare device
      providers in the UK.
AB  - PURPOSE: The telehealthcare sector has been expanding steadily in the UK.
      However, confusing, complex and unwieldy designs of telehealthcare devices are at
      best, less effective than they could be, at worst, they are potentially dangerous
      to the users. METHOD: This study investigated the factors within the new product
      development process that hindered satisfactory product design outcomes, through
      working collaboratively with a leading provider based in the UK. RESULTS: This
      study identified that there are too many costly late-stage design changes; a
      critical and persistent problem area ripe for improvement. The findings from
      analyzing 30 recent devices, interviewing key stakeholders and observing on-going
      projects further revealed that one major cause of the issue was poor practice in
      defining and communicating the product design criteria and requirements.
      CONCLUSIONS: Addressing the characteristics of the telehealthcare industry, such
      as multiple design commissioners and frequent deployment of design subcontracts,
      this paper argues that undertaking a robust process of creating the product
      design brief is the key to improving the outcomes of telehealthcare device
      design, particularly for the small and medium-sized enterprises dominating the
      sector. Implications for rehabilitation Product design criteria and requirements
      are frequently ill-defined and ineffectively communicated to the designers within
      the processes of developing new telehealthcare devices. The absence of a (robust)
      process of creating the design brief is the root cause of the identified issues
      in defining and communicating the design task. Deploying a formal process of
      creating the product design brief is particularly important for the
      telehealthcare sector.

PMID- 29357717
TI  - Nodule size as predictive factor of efficacy of radiofrequency ablation in
      treating autonomously functioning thyroid nodules.
AB  - CONTEXT: No defined pre-treatment factors are able to predict the response to
      radiofrequency ablation (RFA) of an autonomously functioning thyroid nodule
      (AFTN). OBJECTIVE: Primary endpoint was to evaluate the success rate of RFA to
      restore euthyroidism in a cohort of adult patients with small solitary AFTN
      compared with medium-sized nodules. Secondary endpoints included nodule volume
      reduction and rate of conversion from hot nodules to cold using scintiscan.
      METHODS: This was a 24-month prospective monocentric open parallel-group trial.
      Twenty-nine patients with AFTN were divided into two groups based on thyroid
      volume: 15 patients with small nodules (<12 mL) in group A and 14 patients with
      medium nodules (>12 mL) in group B. All patients underwent a single session of
      RFA and were clinically, biochemically, and morphologically evaluated at baseline
      and at 1, 6, 12 and 24 months after treatment. RESULTS: After RFA, there was
      greater nodule volume reduction in group A compared with group B (p < 0.001 for
      each follow-up point). In group A, there was a greater increase in TSH levels
      than in group B at 6 (p = 0.01), 12 (p = 0.005), and 24 months (p < 0.001). At 24
      months, the rate of responders was greater in group A than in group B (86 vs.
      45%; p < 0.001). In group A, 86% of nodules converted from hot to cold compared
      with 18% in group B (p < 0.001). CONCLUSIONS: A single session of RFA was
      effective in restoring euthyroidism in patients with small AFTNs. Nodule volume
      seems to be a significant predictive factor of the efficacy of RFA in treating
      AFTN.

PMID- 29357718
TI  - The cost-effectiveness of dulaglutide versus insulin glargine for the treatment
      of type 2 diabetes mellitus in Japan.
AB  - AIMS: Dulaglutide is a new once weekly glucagon-like peptide-1 (GLP-1) receptor
      agonist administered via a disposable auto-injection pen for the management of
      type 2 diabetes mellitus (T2DM). The objective of this study was to estimate the
      cost-effectiveness of dulaglutide vs insulin glargine for the management of T2DM
      from a Japanese healthcare perspective, in accordance with recently approved
      Japanese Cost-Effectiveness Guidelines. METHODS: The IQVIA CORE Diabetes Model
      (version 9) was used to estimate the long-term costs and effects of treatment
      with dulaglutide and insulin glargine. Direct comparative data from the Araki
      2015 trial (NCT01584232) was used to inform the analysis. Costs associated with
      treatment and complications were derived from Japanese sources wherever possible
      and inflated to 2015 Japanese Yen (JPY). Utilities were based upon a European
      systematic review of diabetes utilities and adjusted for use in a Japanese
      population. One-way and probabilistic sensitivity analyses (OWSA and PSA) were
      conducted on all inputs and key modeling assumptions. RESULTS: Dulaglutide 0.75
      mg was associated with higher quality-adjusted life years (QALYs), life years
      (LYs), and total costs, compared to insulin glargine, resulting in an incremental
      cost-effectiveness ratio (ICER) of 416,280 JPY/QALY gained. Treatment with
      dulaglutide increased the time alive and free from diabetes-related complications
      by 4 months. OWSA and PSA indicated that results were robust to plausible
      variations in input parameters and modeling assumptions. LIMITATIONS: Key
      limitations of this study are similar to other cost-utility analyses of diabetes,
      including the extrapolation of short-term clinical trial data into lifelong
      durations. In addition, due to the lack of robust published Japanese data, some
      values were derived from non-Japanese sources. CONCLUSIONS: This analysis
      suggests that dulaglutide 0.75 mg may be a cost-effective treatment alternative
      to insulin glargine for patients with T2DM in Japan.

PMID- 29357720
TI  - Severity of asphyxia is a covariate of phenobarbital clearance in newborns
      undergoing hypothermia.
AB  - AIM: Phenobarbital (PB) pharmacokinetics (PK) in asphyxiated newborns show large
      variability, not only explained by hypothermia (HT). We evaluated potential
      relevant covariates of PK of PB in newborns treated with or without HT for
      hypoxic-ischemic encephalopathy (HIE). METHODS: Clearance (CL), distribution
      volume (Vd) and elimination half-life (t1/2) were calculated using one
      compartment analysis. Covariates were clinical characteristics (weight,
      gestational age, hepatic, renal, and circulatory status), comedication and HIE
      severity [time to reach normal aEEG pattern (TnormaEEG), dichotomous, within 24
      h] and asphyxia severity [severe aspyhxia = pH <=7.1 + Apgar score <=5 (5 min),
      dichotomous]. Student's t-test, two-way ANOVA, correlation and Pearson's chi
      square test were used. RESULTS: Forty newborns were included [14 non-HT; 26 HT
      with TnormaEEG <24 h in 14/26 (group1-HT) and TnormaEEG >=24 h in 12/26 (group2
      HT)]. Severe asphyxia was present in 26/40 [5/14 non-HT, 11/14 and 10/12 in both
      HT groups]. PB-CL, Vd and t1/2 were similar between the non-HT and HT group.
      However, within the HT group, PB-CL was significantly different between group1-HT
      and group2-HT (p = .043). ANOVA showed that HT (p = .034) and severity of
      asphyxia (p = .038) reduced PB-CL (-50%). CONCLUSION: The interaction of severity
      of asphyxia and HT is associated with a clinical relevant reduced PB-CL,
      suggesting the potential relevance of disease characteristics beyond HT itself.

PMID- 29357719
TI  - Role of Risk of Bias in Systematic Review for Chemical Risk Assessment: A Case
      Study in Understanding the Relationship Between Congenital Heart Defects and
      Exposures to Trichloroethylene.
AB  - The National Academy of Science has recommended that a risk of bias (RoB;
      credibility of the link between exposure and outcome) assessment be conducted on
      studies that are used as primary data sources for hazard identification and dose
      response assessment. Few applications of such have been conducted. Using
      trichloroethylene and congenital heart defects (CHDs) as a case study, we explore
      the role of RoB in chemical risk assessment using the National Toxicology
      Program's Office of Health Assessment and Translation RoB tool. Selected
      questions were tailored to evaluation of CHD and then applied to 12 experimental
      animal studies and 9 epidemiological studies. Results demonstrated that the
      inconsistent findings of a single animal study were likely explained by the
      limitations in study design assessed via RoB (eg, lack of concurrent controls,
      unvalidated method for assessing outcome, unreliable statistical methods, etc).
      Such limitations considered in the context of the body of evidence render the
      study not sufficiently reliable for the development of toxicity reference values.
      The case study highlights the utility of RoB as part of a robust risk assessment
      process and specifically demonstrates the role RoB can play in objectively
      selecting candidate data sets to develop toxicity values.

PMID- 29357721
TI  - Capillary abnormalities observed by nailfold video-capillaroscopy in Japanese
      patients with systemic sclerosis.

PMID- 29357722
TI  - Improving Adherence to Atypical Antipsychotic Agent Screening Guidelines in
      Pediatric Patients: A Quality Improvement Project Within an Integrated Community
      Mental Health Setting.
AB  - BACKGROUND: Approximately 14% to 20% of children and adolescents have a mental
      health problem. Atypical antipsychotic agents are used to treat behavioral,
      emotional, and mental health problems in children and adolescents. A discrepancy
      between best practices and actual practices exists. OBJECTIVE: The purpose of
      this quality improvement project was to increase adherence above baseline,
      through implementation of a checklist, to recommended screening guidelines in
      children, ages 4 to 18, prescribed atypical antipsychotic agents over 12 weeks.
      Design/Results: Aggregate comparison of the mean ranks of scores were tested with
      the Mann-Whitney U test, U = 1,087.5, n1 = n2 = 70, total N =140, p < .001.
      Variables of body mass index, blood pressure, waist circumference, fasting
      glucose, fasting lipids, personal history, and family history were observed and
      tested using the chi-square with Fisher's exact tests and are significant at or
      above 99% confidence level ( p < .01). CONCLUSION: Educating mental health
      providers, child and adolescent psychiatrists, and psychiatric mental health
      nurse practitioners on recommended screening guidelines and implementing a
      checklist had a measurable effect on increasing adherence to the recommended
      screening guidelines in a community mental health setting.

PMID- 29357723
TI  - A Model of Aging Perception in Iranian Elders With Effects of Hope, Life
      Satisfaction, and Socioeconomic Status: A Path Analysis.
AB  - BACKGROUND: Aging perception plays a central role in the experience of healthy
      aging by older people. Research identified that factors such as hope, life
      satisfaction, and socioeconomic status influence the perception of aging in older
      populations. OBJECTIVE: This study sought to test a hypothetical model to
      quantitatively evaluate the relationship between hope, life satisfaction, and
      socioeconomic status with aging perception. DESIGN: A cross-sectional design was
      used with 504 older aged participants who live in Qazvin, Iran. Data were
      collected using the Barker's Aging Perception Questionnaire, Life Satisfaction
      Index-Z, and Herth Hope Index. RESULTS: The results of path analysis showed that
      hope was the most important factor affecting aging perception. Results drawn from
      correlation analysis indicated that there was a positive significant correlation
      ( r = .383, p < .001) between hope and aging perception. Further analysis found
      that hope had the strongest impact on aging perception compared with the other
      variables analyzed (e.g., life satisfaction and socioeconomic status).
      CONCLUSIONS: A model of aging perception in Iranian elders is presented. The
      findings suggested that hope had a significant and positive impact on aging
      perception. Implications for clinical practice and research are discussed.

PMID- 29357725
TI  - Enhanced gene delivery by polyethyleneimine coated mesoporous silica
      nanoparticles.
AB  - Due to large surface area, tunable pore size, easy surface manipulation, and low
      toxicity mesoporous silica nanoparticles (MSNs) may act as a suitable vector for
      gene delivery. In order to make MSNs as a suitable gene delivery system, we
      modified the surface of phosphonated MSNs (PMSN) with polyethyleneimine (PEI) 10
      and 25 KDa. Then nanoparticles were loaded with chloroquine (CQ) (a
      lysosomotropic agent) and complexed with plasmid DNA. The transfection efficiency
      and cytotoxicity of these nanoparticles was examined using green fluorescent
      protein plasmid (pGFP) and cytotoxicity assay. All PEI coated nanoparticles
      showed positive zeta potential and mean size was ranged between 170 and 215 nm
      with polydispersity index bellow 0.35. PEI-coated MSNs significiantly enhanced
      GFP gene expression in Neuro-2 A cells compared to PEI 10 and 25 KDa. The results
      of the cytotoxicity assays showed that these nanoparticles have an acceptable
      level of viability but CQ loaded nanoparticles showed higher cytotoxicity and
      lower transfection activity than CQ free nanoparticles.

PMID- 29357726
TI  - Metabolic characteristics of Tanshinone I in human liver microsomes and S9
      subcellular fractions.
AB  - Tanshinone I (TSI) is a lipophilic diterpene in Salvia miltiorrhiza with
      versatile pharmacological activities. However, metabolic pathway of TSI in human
      is unknown. In this study, we determined major metabolites of TSI using a
      preparation of human liver microsomes (HLMs) by HPLC-UV and Q-Trap mass
      spectrometer. A total of 6 metabolites were detected, which indicated the
      presence of hydroxylation, reduction as well as glucuronidation. Selective
      chemical inhibition and purified cytochrome P450 (CYP450) isoform screening
      experiments revealed that CYP2A6 was primarily responsible for TSI Phase I
      metabolism. Part of generated hydroxylated TSI was glucuronidated via several
      glucuronosyltransferase (UGT) isoforms including UGT1A1, UGT1A3, UGT1A7, UGT1A9,
      as well as extrahepatic expressed isoforms UGT1A8 and UGT1A10. TSI could be
      reduced to a relatively unstable hydroquinone intermediate by NAD(P)H: quinone
      oxidoreductase 1 (NQO1), and then immediately conjugated with glucuronic acid by
      a panel of UGTs, especially UGT1A9, UGT1A1 and UGT1A8. Additionally, NQO1 could
      also reduce hydroxylated TSI to a hydroquinone intermediate, which was
      immediately glucuronidated by UGT1A1. The study demonstrated that hydroxylation,
      reduction as well as glucuronidation were the major pathways for TSI
      biotransformation, and six metabolites generated by CYPs, NQO1 and UGTs were
      found in HLMs and S9 subcellular fractions.

PMID- 29357724
TI  - Prospective analysis of glycemic variability in patients with severe traumatic
      brain injury: modified Leuven's adjustment process versus conventional adjustment
      process.
AB  - Objective This study was performed to evaluate the effect of two different
      methods of controlling glycemic variability (GV) in patients with severe
      traumatic brain injury (STBI) undergoing surgery. Methods Patients with STBI were
      randomly grouped into a conventional adjustment process (CAP) group and modified
      Leuven's adjustment process (mLAP) group. Each group included 50 patients. Blood
      glucose levels were continuously monitored and data were recorded and analyzed.
      Results The mean blood glucose level was stable in both groups for 5 days
      postoperatively with no significant difference. The standard deviation of the
      blood glucose level, mean amplitude of glycemic excursions, and glycemic lability
      index were significantly higher in the CAP than mLAP group for the first 2 days.
      In the final 3 days, no significant differences were observed between the two
      groups. The incidence of hypoglycemia was significantly higher in the CAP than
      mLAP group on the first day. This value gradually declined during the following 4
      days, but the difference between the two groups was not significant. Conclusion
      The mLAP produced more favorable results than the CAP for GV control in the early
      stage after surgery for STBI.

PMID- 29357727
TI  - Amniotic fluid HIF1alpha and exosomal HIF1alpha in cervical insufficiency
      patients with physical examination-indicated cerclage.
AB  - OBJECTIVE: Hypoxia inducible factor 1alpha (HIF1alpha) has been reported to
      activate inflammatory cascade. Recently, exosomes have been known to have pivotal
      roles in intercellular communication. The aim of this study was to compare the
      concentration of amniotic fluid (AF) HIF1alpha, exosomal HIF1alpha, and
      inflammatory cytokines such as interleukin 1alpha (IL1alpha), interleukin 1beta
      (IL1beta), interleukin 6 (IL6), and tumor necrosis factor alpha (TNFalpha)
      between physical examination-indicated cerclage (PEIC) and control group. We also
      investigated the associations between biomarkers and amniocentesis-to-delivery
      interval and the correlations of inflammatory cytokines, HIF1alpha, and exosomal
      HIF1alpha. METHODS: Case-control study was performed. Cases are defined as 16
      patients who underwent PEIC and controls are 19 women who underwent amniocentesis
      for confirming chromosomal abnormalities. The concentration of IL1alpha, IL1beta,
      IL6, TNFalpha, HIF1alpha, and exosomal HIF1alpha were measured using enzyme
      linked immunosorbent assay (ELISA). Exosomes were confirmed by tumor
      susceptibility Gene 101 (TSG 101) and transmission electron microscopy (TEM).
      RESULTS: The mean HIF1alpha in PEIC group was higher than control group (PEIC,
      15.03 +/- 9.60-pg/mL versus control, 2.96 +/- 1.99 pg/mL; p < .01). There were
      significant differences in inflammatory cytokines between two groups. A
      significant difference in exosomal HIF1alpha was shown between two groups (PEIC,
      27.97 +/- 28.61-ug/mL versus control, 12.42 +/- 8.20 ug/mL; p < .01). HIF1alpha,
      IL1alpha, IL6, TNFalpha, and exosomal HIF1alpha showed significantly negative
      association with cerclage-to-delivery interval. However, IL1beta was not
      associated with cerclage-to-delivery interval. HIF1alpha was positively
      correlated with exosomal HIF1alpha (rho = 0.93, p < .01). Both HIF1alpha and
      exosomal HIF1alpha were significantly associated with TNFalpha (rho = 0.94, p <
      .01; rho = 0.97, p < .01). Both HIF-1alpha and exosomal HIF1alpha had positive
      correlation with IL1alpha (rho = 0.96, p < .01; rho = 0.91, p < .01). However,
      IL1beta showed no correlations with HIF1alpha and exosomal HIF1alpha. A positive
      correlation between HIF-1alpha and IL6 was observed (rho = 0.58, p = .01.)
      Exosomal HIF1alpha also had correlation with IL6 (rho = 0.52, p = .03).
      CONCLUSIONS: This study demonstrated that amniotic fluid (AF) HIF1alpha and AF
      exosomal HIF1alpha were higher in physical examination-indicated cerclage (PEIC)
      group than control group. AF HIF1alpha and AF exosomal HIF1alpha were associated
      with shorter amniocentesis-to-delivery interval. More importantly, they had
      positive correlations with AF inflammatory cytokines such as IL1alpha, IL6, and
      TNFalpha. Our results may indicate that AF HIF1alpha and AF exosomes interact
      with AF inflammatory cytokines and contribute inflammatory cascade in complicated
      pregnancies.

PMID- 29357728
TI  - Implementation of selective prevention for cardiometabolic diseases; are Dutch
      general practices adequately prepared?
AB  - OBJECTIVE: Current guidelines acknowledge the need for cardiometabolic disease
      (CMD) prevention and recommend five-yearly screening of a targeted population. In
      recent years programs for selective CMD-prevention have been developed, but
      implementation is challenging. The question arises if general practices are
      adequately prepared. Therefore, the aim of this study is to assess the
      organizational preparedness of Dutch general practices and the facilitators and
      barriers for performing CMD-prevention in practices currently implementing
      selective CMD-prevention. DESIGN: Observational study. SETTING: Dutch primary
      care. SUBJECTS: General practices. MAIN OUTCOME MEASURES: Organizational
      characteristics. RESULTS: General practices implementing selective CMD-prevention
      are more often organized as a group practice (49% vs. 19%, p = .000) and are
      better organized regarding chronic disease management compared to reference
      practices. They are motivated for performing CMD-prevention and can be considered
      as 'frontrunners' of Dutch general practices with respect to their practice
      organization. The most important reported barriers are a limited availability of
      staff (59%) and inadequate funding (41%). CONCLUSIONS: The organizational
      infrastructure of Dutch general practices is considered adequate for performing
      most steps of selective CMD-prevention. Implementation of prevention programs
      including easily accessible lifestyle interventions needs attention. All
      stakeholders involved share the responsibility to realize structural funding for
      programmed CMD-prevention. Aforementioned conditions should be taken into account
      with respect to future implementation of selective CMD-prevention. Key Points  
      There is need for adequate CMD prevention. Little is known about the organization
      of selective CMD prevention in general practices.   * The organizational
      infrastructure of Dutch general practices is adequate for performing most steps
      of selective CMD prevention.   * Implementation of selective CMD prevention
      programs including easily accessible services for lifestyle support should be the
      focus of attention.   * Policy makers, health insurance companies and healthcare
      professionals share the responsibility to realize structural funding for
      selective CMD prevention.

PMID- 29357729
TI  - Evaluation of Time Spent by Pharmacists and Nurses Based on the Location of
      Pharmacist Involvement in Medication History Collection.
AB  - BACKGROUND: Accurate history collection is integral to medication reconciliation.
      Studies support pharmacy involvement in the process, but assessment of global
      time spent is limited. The authors hypothesized the location of a medication
      focused interview would impact time spent. METHODS: The objective was to compare
      time spent by pharmacists and nurses based on the location of a medication
      focused interview. Time spent by the interviewing pharmacist, admitting nurse,
      and centralized pharmacist verifying admission orders was collected. Patient
      groups were based on whether the interview was conducted in the emergency
      department (ED) or medical floor. The primary end point was a composite of the 3
      time points. Secondary end points were individual time components and number and
      types of transcription discrepancies identified during medical floor interviews.
      RESULTS: Pharmacists and nurses spent an average of ten fewer minutes per ED
      patient versus a medical floor patient ( P = .028). Secondary end points were not
      statistically significant. Transcription discrepancies were identified at a rate
      of 1 in 4 medications. Post hoc analysis revealed the time spent by pharmacists
      and nurses was 2.4 minutes shorter per medication when interviewed in the ED ( P
      < .001). DISCUSSION: The primary outcome was statistically and clinically
      significant. Limitations included inability to blind and lack of cost-saving
      analysis. CONCLUSION: Pharmacist involvement in ED medication reconciliation
      leads to time savings during the admission process.

PMID- 29357730
TI  - Rates of Exposure to Victimizing Events and Use of Substances Among California's
      Middle and High School Students.
AB  - Nearly half of 5- to 17-year-olds have experienced trauma in the form of at
      school victimization. Exposure to trauma increases students' risk for mental
      health disorders and school failure. This study reviews at-school victimization
      in middle and high school students and associated health outcomes that may
      negatively impact academic outcomes. Analyzing the California Healthy Kids Survey
      2010, we examine rates of victimization on school grounds, substance use, and
      symptoms of depression and eating disorders among a sample of 6th to 12th graders
      ( N = 639,925). Between 20% and 50% of students had experienced at least one type
      of victimizing event on school grounds, with the highest incidence in middle
      schools. A significantly higher share of victimized students reported using
      substances, symptoms of depression and eating disorders when compared to
      nonvictimized students. School district investment in school nurses, social
      workers, and school-based health centers could increase preventive interventions
      to improve school climate, student well-being, and academic success.

PMID- 29357731
TI  - Medullary Astrogliosis in Sudden Infant Death Syndrome Varies With Sleeping
      Environment: Evidence for Different Mechanisms of Death in Alone Versus Co
      sleepers?
AB  - Sudden infant death syndrome remains the leading cause of death in infants under
      1 year, and underlying pathophysiological mechanisms are poorly understood. The
      current study investigated the hypothesis that co-sleepers die more rapidly from
      causes such as suffocation from overlaying by comparing levels of reactive
      astrogliosis in the medulla of infants who died sleeping alone to those who died
      co-sleeping. The amount of glial fibrillary acidic protein (GFAP) staining in
      alone sleepers was significantly higher than shared sleepers in 3 specific areas
      of the medulla, the inferior vestibular nucleus, the medial vestibular nucleus
      and the cochlear nucleus. Given that glial fibrillary acidic protein elevations
      follow a delayed time course, this suggests that death in co-sleepers was more
      rapid, not allowing for reactive gliosis to occur. This provides evidence of
      pathological differences in mechanisms of death in infants who are classified as
      having died from sudden infant death syndrome, suggesting potential need for
      refinement of categorization of these cases.

PMID- 29357733
TI  - Effects of glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its
      potential mechanism.
AB  - CONTEXT: Asiatic acid has been reported to possess a wide range of
      pharmacological activities. OBJECTIVE: This study investigates the effects of
      glycyrrhizin on the pharmacokinetics of asiatic acid in rats and its potential
      mechanism. MATERIALS AND METHODS: The pharmacokinetics of orally administered
      asiatic acid (20 mg/kg) with or without glycyrrhizin pretreatment (100 mg/kg/day
      for seven days) were investigated using a LC-MS method. Additionally, the Caco-2
      cell transwell model and rat liver microsome incubation systems were used to
      investigate the potential mechanism of glycyrrhizin's effects on the
      pharmacokinetics of asiatic acid. RESULTS: The results showed that the Cmax
      (221.33 +/- 21.06 vs. 324.67 +/- 28.64 ng/mL), AUC0-inf (496.12 +/- 109.31 vs.
      749.15 +/- 163.95 MUg.h/L) and the t1/2 (1.21 +/- 0.27 vs. 2.04 +/- 0.32 h) of
      asiatic acid decreased significantly (p < 0.05) with the pretreatment of
      glycyrrhizin. The oral clearance of asiatic acid increased significantly from
      27.59 +/- 5.34 to 41.57 +/- 9.19 L/h/kg (p < 0.05). The Caco-2 cell transwell
      experiments indicated that glycyrrhizin could increase the efflux ratio of
      asiatic acid from 1.63 to 2.74, and the rat liver microsome incubation
      experiments showed that glycyrrhizin could increase the intrinsic clearance rate
      of asiatic acid from 138.32 +/- 11.20 to 221.76 +/- 16.85 MUL/min/mg protein.
      DISCUSSION AND CONCLUSIONS: In conclusion, these results indicated that
      glycyrrhizin could decrease the system exposure of asiatic acid, possibly by
      inducing the activity of P-gp or CYP450 enzyme.

PMID- 29357732
TI  - Activation of ventral tegmental area dopaminergic neurons reverses pathological
      allodynia resulting from nerve injury or bone cancer.
AB  - Chronic pain induced by nerve damage due to trauma or invasion of cancer to the
      bone elicits severe ongoing pain as well as hyperalgesia and allodynia likely
      reflecting adaptive changes within central circuits that amplify nociceptive
      signals. The present study explored the possible contribution of the mesolimbic
      dopaminergic circuit in promoting allodynia related to neuropathic and cancer
      pain. Mice with ligation of the sciatic nerve or treated with intrafemoral
      osteosarcoma cells showed allodynia to a thermal stimulus applied to the paw on
      the injured side. Patch clamp electrophysiology revealed that the intrinsic
      neuronal excitability of ventral tegmental area (VTA) dopamine neurons projecting
      to the nucleus accumbens (N.Acc.) was significantly reduced in those mice. We
      used tyrosine hydroxylase (TH)-cre mice that were microinjected with adeno
      associated virus (AAV) to express channelrhodopsin-2 (ChR2) to allow optogenetic
      stimulation of VTA dopaminergic neurons in the VTA or in their N.Acc. terminals.
      Optogenetic activation of these cells produced a significant but transient anti
      allodynic effect in nerve injured or tumor-bearing mice without increasing
      response thresholds to thermal stimulation in sham-operated animals. Suppressed
      activity of mesolimbic dopaminergic neurons is likely to contribute to decreased
      inhibition of N.Acc. output neurons and to neuropathic or cancer pain-induced
      allodynia suggesting strategies for modulation of pathological pain states.

PMID- 29357734
TI  - Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in
      Increased Proliferation of Neural Stem Cells.
AB  - In the quest to unravel its functional significance, neuroglobin (Ngb), a brain
      specific neuroprotective protein, has recently been proposed as an actor in
      neurodevelopment. As neural stem cells (NSCs) are fundamental during brain
      development, the present study aimed at investigating the role of Ngb in the
      growth and proliferation of NSCs by comparing an Ngb-floxed (Ngbfl-)NSC line,
      equivalent to the wild-type cellular situation, with an in-house created Ngb
      knockout (NgbKO-)NSC line. NgbKO-NSCs were characterized by an increased growth
      and proliferation capacity in vitro, supported by RNA sequencing and western blot
      results reporting the downregulation of Cdkn1a and the upregulation of Cdk6, both
      enhancing the cell cycle. Based on additional gene ontology enrichment and
      pathway analyses, we hypothesize that the loss of Ngb affects multiple cellular
      signaling pathways with the most important being the Akt-Tp53 axis.

PMID- 29357735
TI  - Niche point-of-care endocrine testing - Reviews of intraoperative parathyroid
      hormone and cortisol monitoring.
AB  - Point-of-care (POC) testing, which provides quick test results in near-patient
      settings with easy-to-use devices, has grown continually in recent decades. Among
      near-patient and on-site tests, rapid intraoperative and intra-procedural assays
      are used to quickly deliver critical information and thereby improve patient
      outcomes. Rapid intraoperative parathyroid hormone (ioPTH) monitoring measures
      postoperative reduction of parathyroid hormone (PTH) to predict surgical outcome
      in patients with primary hyperparathyroidism, and therefore contributes to the
      change of parathyroidectomy to a minimally invasive procedure. In this review,
      recent progress in applying ioPTH monitoring to patients with secondary and
      tertiary hyperparathyroidism and other testing areas is discussed. In-suite
      cortisol monitoring facilitates the use of adrenal vein sampling (AVS) for the
      differential diagnosis of primary aldosteronism and adrenocorticotropic hormone
      (ACTH)-independent Cushing syndrome. In clinical and psychological research
      settings, POC testing is also useful for rapidly assessing cortisol in plasma and
      saliva samples as a biomarker of stress. Careful resource utilization and
      coordination among stakeholders help to determine the best approach for
      implementing cost-effective POC testing. Technical advances in integrating
      appropriate biosensors with microfluidics-based devices hold promise for future
      real-time POC cortisol monitoring.

PMID- 29357736
TI  - Circular RNA Expression Profiles Alter Significantly after Traumatic Brain Injury
      in Rats.
AB  - Circular RNAs (circRNAs) are involved in a variety of diseases. However, the
      roles of circRNAs in traumatic brain injury (TBI) remain unknown. In this study,
      circRNA microarray was used to profile the altered circRNAs in the rat
      hippocampus following TBI. A total of 192 circRNAs were observed to be
      differentially expressed (fold change [FC] >=1.5 and p < 0.05) after TBI,
      including 98 upregulated and 94 downregulated. Gene ontology (GO) and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many
      messenger RNAs (mRNAs) transcribed from the host genes of altered circRNAs were
      implicated in brain damage and neural regeneration. CircRNA/microRNA (miRNA)
      interaction was predicted using Arraystar's homemade miRNA target prediction
      software based on TargetScan and miRanda. Thus, our studies have demonstrated
      altered circRNA expression pattern in the rat hippocampus after TBI, which may
      play important roles in post-TBI physiological and pathological processes. These
      findings may provide not only a new direction for studying the molecular
      mechanisms underlying TBI but also a new possibility for the treatment of TBI by
      modulating circRNAs.

PMID- 29357737
TI  - Lifesaving in Every Way: The Role of Companion Animals in the Lives of Older
      Lesbian, Gay, Bisexual, and Transgender Adults Age 50 and Over.
AB  - This study uses mixed-methods data and a life-course perspective to explore the
      role of pets in the lives of lesbian, gay, bisexual, and transgender (LGBT)
      adults age 50 and over and addresses the following research questions: (1) How
      does having a pet relate to perceived social support and social network size? and
      (2) how do LGBT older adults describe the meaning of pets in their lives? The
      qualitative data ( N = 59) were collected from face-to-face interviews, and the
      quantitative data ( N = 2,560) were collected via surveys from a sample across
      the United States. Qualitative findings show that pets are characterized as kin
      and companions and provide support; we also explore why participants do not have
      pets. The quantitative findings show that LGBT older adults with a pet had higher
      perceived social support; those with a disability and limited social network
      size, who had a pet had significantly higher perceived social support than those
      without a pet.

PMID- 29357738
TI  - Estimating Putting Outcomes in Golf: Experts Have a Better Sense of Distance.
AB  - In putting, golfers require an internal forward sense of the causal relationship
      between putting actions and outcomes-a sense of distance-to decide appropriate
      impact intensity. As no previous work has shown such a cognitive ability in
      skilled golfers, we sought to quantify sense-of-distance skill differences
      between experts and novice golfers in both putting-swing consistency and accuracy
      of outcome estimation. We compared nine expert and nine novice golfers on putting
      outcome estimation by having them putt a golf ball to a target located at three
      distances (1.2, 2.4, and 3.6 m), and then, after automatic closure of their
      electric-shutter spectacles immediately following putter impact with the ball,
      they gave their best estimate of where the ball stopped. We assessed outcome
      estimation accuracy by calculating the absolute error between the stopped ball's
      actual and estimated positions. We also measured and analyzed putter head-swing
      movements during the task using a motion-capture system. Two-way, mixed-design
      analysis of variance tests revealed that expert golfers achieved both
      significantly lower variability in putter-head kinematics and higher accuracy at
      outcome estimation than the novices. Linear partial correlation analyses with
      target distance as the control variable tested the relationship between outcome
      estimation performance and putter-head variability kinematic measurements. There
      were no significant correlations between them for experts and novices in separate
      databases, while medium correlations were found in a collective database. Thus,
      swing consistency and a sense of distance are independent skills that both
      account for putting expertise, and specific training is required for each to
      improve putting skills.

PMID- 29357739
TI  - Grafts of Olfactory Stem Cells Restore Breathing and Motor Functions after Rat
      Spinal Cord Injury.
AB  - The transplantation of olfactory ecto-mesenchymal stem cells (OEMSCs) could be a
      helpful therapeutic strategy for spinal cord repair. Using an acute rat model of
      high cervical contusion that provokes a persistent hemidiaphragmatic and foreleg
      paralysis, we evaluated the therapeutic effect of a delayed syngeneic
      transplantation (two days post-contusion) of OEMSCs within the injured spinal
      cord. Respiratory function was assessed using diaphragmatic electromyography and
      neuroelectrophysiological recordings of phrenic nerves (innervating the
      diaphragm). Locomotor function was evaluated using the ladder-walking locomotor
      test. Cellular reorganization in the injured area was also studied using
      immunohistochemical and microscopic techniques. We report a substantial
      improvement in breathing movements, in activities of the ipsilateral phrenic
      nerve and ipsilateral diaphragm, and also in locomotor abilities four months post
      transplantation with nasal OEMSCs. Moreover, in the grafted spinal cord, axonal
      disorganization and inflammation were reduced. Some grafted stem cells adopted a
      neuronal phenotype, and axonal sparing was observed in the injury site. The
      therapeutic effect on the supraspinal command is presumably because of both
      neuronal replacements and beneficial paracrine effects on the injury area. Our
      study provides evidence that nasal OEMSCs could be a first step in clinical
      application, particularly in patients with reduced breathing/locomotor movements.

PMID- 29357740
TI  - Retention interval modulates the effect of negative arousing pictures on
      recognition memory.
AB  - This study examined the modulation of retention interval in the effect of emotion
      as elicited from negative and positive arousing pictures on recognition memory.
      Participants underwent seven encoding sessions and one testing session. The
      encoding sessions were separated by certain lengths of intervals such that there
      were seven levels of time gaps between encoding and testing. In each encoding
      session, participants learned a list of 30 pictures (including 10 neutral, 10
      positive and 10 negative pictures). In the testing session, they were presented
      with a list of 210 old and 210 new pictures and made "old/new" and
      "remember/know" judgements. The results showed that negative arousing pictures
      enhanced overall recognition in the 2-week interval and enhanced recollection in
      both the 2-week and 3-week intervals. However, neither negative nor positive
      arousing pictures had any effect on familiarity regardless of retention interval.
      The current study contributes to the literature by suggesting that longer
      retention intervals do not necessarily lead to more pronounced effects of
      negative arousing pictures and that the modulation of retention interval depends
      on the specific components of recognition memory.

PMID- 29357741
TI  - Clinical Validation of Eye Vergence as an Objective Marker for Diagnosis of ADHD
      in Children.
AB  - OBJECTIVE: ADHD youth show poor oculomotor control. Recent research shows that
      attention-related eye vergence is weak in ADHD children. METHOD: To validate
      vergence as a marker to classify ADHD, we assessed the modulation in the angle of
      vergence of children ( n = 43) previously diagnosed with ADHD while performing an
      attention task and compared the results with age-matched clinical controls ( n =
      19) and healthy peers ( n = 30). RESULTS: We observed strong vergence responses
      in healthy participants and weak vergence in the clinical controls. ADHD children
      showed no significant vergence responses. Machine-learning models classified ADHD
      patients ( n = 21) from healthy controls ( n = 21) with an accuracy of 96.3%
      (false positive [FP]: 5.12%; false negative [FN]: 0%; area under the curve [AUC]:
      0.99) and ADHD children ( n = 11) from clinical controls ( n = 14) with an
      accuracy of 85.7% (FP: 4.5%; FN: 19.2%, AUC: 0.90). CONCLUSION: In combination
      with an attention task, vergence responses can be used as an objective marker to
      detect ADHD in children.

PMID- 29357742
TI  - Ecological Virtual Reality Evaluation of Neglect Symptoms (EVENS): Effects of
      Virtual Scene Complexity in the Assessment of Poststroke Unilateral Spatial
      Neglect.
AB  - BACKGROUND: Unilateral spatial neglect (USN) is a highly prevalent and disabling
      poststroke impairment. USN is traditionally assessed with paper-and-pencil tests
      that lack ecological validity, generalization to real-life situations and are
      easily compensated for in chronic stages. Virtual reality (VR) can, however,
      counteract these limitations. OBJECTIVE: We aimed to examine the feasibility of a
      novel assessment of USN symptoms in a functional shopping activity, the
      Ecological VR-based Evaluation of Neglect Symptoms (EVENS). METHODS: EVENS is
      immersive and consists of simple and complex 3-dimensional scenes depicting
      grocery shopping shelves, where joystick-based object detection and navigation
      tasks are performed while seated. Effects of virtual scene complexity on
      navigational and detection abilities in patients with (USN+, n = 12) and without
      (USN-, n = 15) USN following a right hemisphere stroke and in age-matched healthy
      controls (HC, n = 9) were determined. RESULTS: Longer detection times, larger
      mediolateral deviations from ideal paths and longer navigation times were found
      in USN+ versus USN- and HC groups, particularly in the complex scene. EVENS
      detected lateralized and nonlateralized USN-related deficits, performance
      alterations that were dependent or independent of USN severity, and performance
      alterations in 3 USN- subjects versus HC. CONCLUSION: EVENS' environmental
      changing complexity, along with the functional tasks of far space detection and
      navigation can potentially be clinically relevant and warrant further empirical
      investigation. Findings are discussed in terms of attentional models, lateralized
      versus nonlateralized deficits in USN, and tasks-specific mechanisms.

PMID- 29357743
TI  - Evidence for Training-Dependent Structural Neuroplasticity in Brain-Injured
      Patients: A Critical Review.
AB  - Acquired brain injury (ABI) is associated with a range of cognitive and motor
      deficits, and poses a significant personal, societal, and economic burden.
      Rehabilitation programs are available that target motor skills or cognitive
      functioning. In this review, we summarize the existing evidence that training may
      enhance structural neuroplasticity in patients with ABI, as assessed using
      structural magnetic resonance imaging (MRI)-based techniques that probe
      microstructure or morphology. Twenty-five research articles met key inclusion
      criteria. Most trials measured relevant outcomes and had treatment benefits that
      would justify the risk of potential harm. The rehabilitation program included a
      variety of task-oriented movement exercises (such as facilitation therapy,
      postural control training), neurorehabilitation techniques (such as constraint
      induced movement therapy) or computer-assisted training programs (eg, Cogmed
      program). The reviewed studies describe regional alterations in white matter
      architecture and/or gray matter volume with training. Only weak-to-moderate
      correlations were observed between improved behavioral function and structural
      changes. While structural MRI is a powerful tool for detection of longitudinal
      structural changes, specific measures about the underlying biological mechanisms
      are lacking. Continued work in this field may potentially see structural MRI
      metrics used as biomarkers to help guide treatment at the individual patient
      level.

PMID- 29357744
TI  - Skin-limited arteritis of small muscular arteries with giant cell-rich
      granulomatous inflammation in a patient with polymyalgia rheumatica.

PMID- 29357746
TI  - Fertility and union formation during crisis and societal consolidation in the
      Western Balkans.
AB  - Fertility decline in central and eastern Europe (CEE) since the fall of the
      communist regimes has been driven by both stopping and postponement of
      childbearing: two processes that have been related to crisis and economic
      development, respectively. In the Western Balkans these economic and political
      contexts followed each other in the form of a biphasic transition. I examine
      whether this sequence triggered fertility responses like those observed
      elsewhere. Relying on three independent data sources, I cross-validate the levels
      of, and describe the trends in, union formation and fertility (by birth order)
      between 1980 and 2010. Results do not reveal widespread declines in fertility to
      lowest-low levels during the most acute period of crisis. The subsequent
      postponement of marriage and first birth was also limited, and the two-child
      family remains the norm. This relative resilience of childbearing patterns
      compared with other CEE countries is discussed with reference to the
      institutional context.

PMID- 29357745
TI  - Targeting HER2 in Nuclear Medicine for Imaging and Therapy.
AB  - Since its discovery, the human epidermal growth factor 2 (HER2) has been
      extensively studied. Presently, there are 2 standard diagnostic techniques to
      assess HER2 status in biopsies: immunohistochemistry and fluorescence in situ
      hybridization. While these techniques have played an important role in the
      treatment of patients with HER2-positive cancer, they both require invasive
      biopsies for analysis. Moreover, the expression of HER2 is heterogeneous in
      breast cancer and can change over the course of the disease. Thus, the degree of
      HER2 expression in the small sample size of biopsied tumors at the time of
      analysis may not represent the overall status of HER2 expression in the whole
      tumor and in between tumor foci in the metastatic setting as the disease
      progresses. Unlike biopsy, molecular imaging using probes against HER2 allows for
      a noninvasive, whole-body assessment of HER2 status in real time. This technique
      could potentially select patients who may benefit from HER2-directed therapy and
      offer alternative treatments to those who may not benefit. Several antibodies and
      small molecules against HER2 have been labeled with different radioisotopes for
      nuclear imaging and/or therapy. This review presents the most recent advances in
      HER2 targeting in nuclear medicine focusing on preclinical and clinical studies.

PMID- 29357747
TI  - Does Gender Moderate the Relationship Between Social Capital and Life
      Satisfaction? Evidence From Urban China.
AB  - The present study aimed to test the moderating effect of gender on the
      relationship between social capital and life satisfaction among older adults in
      urban China. A quota sampling method was used to select 456 older adults aged 60
      and older from 16 local communities in Suzhou city in 2015. Hierarchical multiple
      regression was employed to test the proposed models. The associations between
      family social capital and life satisfaction were higher among older men than
      women. Trust and helping others were stronger predictors of older women's life
      satisfaction than their male counterparts. Citizenship activities affected life
      satisfaction among older men only. The findings highlight the important role of
      social capital in sustaining and/or improving life satisfaction among both older
      women and men. Policy and intervention implications are discussed.

PMID- 29357749
TI  - Parents' Perspectives of Changes Within the Family Functioning After a Pediatric
      Cancer Diagnosis: A Multi Family Member Interview Analysis.
AB  - Pediatric cancer is a life-threatening disease that challenges the life of the
      diagnosed child, the parents, and possible siblings. Moreover, it also places
      considerable demands on family life. The aim of this study was to explore changes
      in the family functioning after a pediatric cancer diagnosis. Ten couples who had
      a child with leukemia or non-Hodgkin lymphoma were interviewed individually about
      their experiences. Interviews were semistructured, and the data were analyzed
      using Multi Family Member Interview Analysis. Three themes emerged from the data:
      (a) Family Cohesion: Strengthened Versus Fragmented; (b) Educational Norms and
      Values: Overindulgence Versus Being Stricter, and (c) Normality: Loss Versus
      Preservation. The conflicting dynamics present in these emerging themes exemplify
      the complexity of this process of family adaptation. This study illustrates the
      need to take into account the family level, as well as the conflicting feelings
      parents may experience after a pediatric cancer diagnosis.

PMID- 29357748
TI  - Nursing Practice in Primary Care and Patients' Experience of Care.
AB  - PURPOSE: Nurses are identified as a key provider in the management of patients in
      primary care. The objective of this study was to evaluate patients' experience of
      care in primary care as it pertained to the nursing role. The aim was to test the
      hypothesis that, in primary health care organizations (PHCOs) where patients are
      systematically followed by a nurse, and where nursing competencies are therefore
      optimally used, patients' experience of care is better. METHOD: Based on a cross
      sectional analysis combining organizational and experience of care surveys, we
      built 2 groups of PHCOs. The first group of PHCOs reported having a nurse who
      systematically followed patients. The second group had a nurse who performed a
      variety of activities but did not systematically follow patients. Five indicators
      of care were constructed based on patient questionnaires. Bivariate and
      multivariate linear mixed models with random intercepts and with patients nested
      within were used to analyze the experience of care indicators in both groups.
      RESULTS: Bivariate analyses revealed a better patient experience of care in PHCOs
      where a nurse systematically followed patients than in those where a nurse
      performed other activities. In multivariate analyses that included adjustment
      variables related to PHCOs and patients, the accessibility indicator was found to
      be higher. CONCLUSION: Results indicated that systematic follow-up of patients by
      nurses improved patients' experience of care in terms of accessibility. Using
      nurses' scope of practice to its full potential is a promising avenue for
      enhancing both patients' experience of care and health services efficiency.

PMID- 29357750
TI  - The Weight of Things: Understanding African American Women's Perceptions of
      Health, Body Image, and Attractiveness.
AB  - Negative attitudes toward being overweight or obese are widespread, and these
      notions perpetuate into conceptions about one's health. Clinically, being
      overweight is associated with health problems such as diabetes, hypertension,
      heart disease, and many other illnesses. African American women, who are
      generally larger in body size, are a particular target for health interventions.
      However, these women have resisted the "obesity" label, arguing that dominant
      measures of health are White norms and oppressive. Through the use of in-depth
      interviews, this study investigates how African American women understand and
      experience healthfulness, body image, and barriers to each. Findings show that
      African American women are ambivalent in their acceptance of dominant markers of
      health and expressed an almost universal disdain for the thin ideal as a marker
      of "good" health and a positive body image. Moreover, participants articulated a
      suspicion of formal medical measurements of obesity.

PMID- 29357751
TI  - Navigating the Dangerous Terrain of Moral Distress: Understanding Response
      Patterns in the NICU.
AB  - Moral distress is a well-recognized and ubiquitous aspect of health care
      professional practice in the neonatal intensive care unit (NICU) context. We used
      interpretive description methodology to guide a critical exploration of the
      dynamics of moral distress experience as reflected in the accounts of 28 health
      care professionals working in this setting. We learned about the kinds of
      clinical scenarios which triggered distressing experiences, and that the
      organizational and relational context of clinical work constituted a complex and
      dynamic working environment that profoundly affected both the individual and the
      collective experiences with moral distress in these situations. These findings
      shed light on possibilities for supporting NICU practitioners and developing the
      collaborative team cultures that may reduce the risk of unresolved effects of
      moral distress to the benefit of patients as well as the professionals who care
      for them.

PMID- 29357752
TI  - Prevention of minor myocardial injury after elective percutaneous coronary
      intervention: comparison of ticagrelor versus clopidogrel.
AB  - BACKGROUND: Elective percutaneous coronary intervention (ePCI) may cause minor
      elevation of cardiac enzymes, so-called minor myocardial injury (MMI) which can
      be due to different pathophysiological mechanism (e.g. distal embolisation, side
      branch occlusion, increased platelet activation triggered by the intracoronary
      metallic stents). We aimed to compare the effectiveness of ticagrelor versus
      clopidogrel for the prevention of MMI and major adverse clinical events (MACEs)
      after ePCI. METHODS: Study population consisted of two groups of patients based
      on the treatment: Group I, receiving clopidogrel (n = 104), Group II, receiving
      ticagrelor (n = 96). Cardiac troponin I (cTnI), CK-MB were studied before and 12
      hours after the procedure. Elevation of cTnI greater than 0.06 ng/ml was
      considered as MMI. All patients were also evaluated for the MACEs (death,
      myocardial infarction, stroke and transient ischaemic attack). RESULTS: Fifty-two
      of 200 patients (26%) had MMI after the procedure. The minor myocardial injury
      was significantly more prevalent in clopidogrel group than that of ticagrelor
      group (33% vs. 19%, p = .03). Myocardial infarction (MI) and MACEs were
      significantly higher in the clopidogrel group (15% vs. 6%, for MI, p = .04; 16%
      vs. 6%, for MACEs, p = .03, respectively). Multivariate analysis demonstrated
      antiplatelet treatment, saphenous graft intervention, type-C lesion as
      independent predictors of MMI. CONCLUSIONS: Present study showed that the
      combination of ticagrelor and aspirin was more effective than combination of
      clopidogrel and aspirin in decreasing MMI and MACEs after elective stenting.

PMID- 29357753
TI  - Coil Embolization of a Renal Aneurysm Using a Minimally Invasive Endovascular
      Robotic System.
AB  - We present a case demonstrating the use of an endovascular robotic system in the
      treatment of a saccular renal artery aneurysm located at the renal hilum in a
      young patient.

PMID- 29357754
TI  - Attitudes Toward Euthanasia for Patients Who Suffer From Physical or Mental
      Illness.
AB  - This study examined whether attitudes toward euthanasia vary with type of illness
      and with the source of the desire to end the patient's life. The study used a 3
      (illness type: cancer, schizophrenia, depression) * 2 (euthanasia type: patient
      initiated, family-initiated) between-groups experimental design. An online
      questionnaire was administered to 324 employees and students from a Australian
      public university following random assignment of participants to one of the six
      vignette-based conditions. Attitudes toward euthanasia were more positive for
      patients with a physical illness than a mental illness. For a patient with cancer
      or depression, but not schizophrenia, approval was greater for patient-, than,
      family-, initiated euthanasia. Relationships between illness type and attitudes
      were mediated by perceptions of patient autonomy and illness controllability.
      Findings have implications for debate, practices, and legislation regarding
      euthanasia.

PMID- 29357755
TI  - Grief and Healing Trajectories of Drug-Death-Bereaved Parents.
AB  - We explored parents' views of the trajectories of their adult children's eventual
      deaths from drugs with in-depth qualitative interviews from 11 bereaved parents.
      Parents reported great emotional distress and high financial burdens as their
      children went through death spirals of increasing drug involvements. These deaths
      often entailed anxiety-inducing interactions with police or medical personnel,
      subsequent difficulties with sharing death cause information with socially
      significant others, and longer term problems from routine interactions.
      Eventually, though, many of these longer term bereaved parents reported
      overcoming these obstacles and developing posttraumatic growth. Openly disclosing
      the nature of the death seemed to be an important building block for their
      healing.

PMID- 29357756
TI  - The Relationship Between Practice Environment and Psychological Ownership in
      Advanced Practice Nurses.
AB  - Barriers in advanced practice nurses' work environment impede effective use in
      acute care settings, reduce job satisfaction, and increase intent to leave.
      Fostering psychological ownership for work through improved work design has
      increased satisfaction, motivation, and productivity, and lowered turnover in
      other fields, and may have similar effects for advanced practice nurses. This
      multilevel cross-sectional survey study examined the relationship between
      advanced practice nurse work environment and psychological ownership using data
      from a survey of advanced practice nurses and nurse executives in Florida
      hospitals. Barriers in scope of practice and exclusion from hospital governance
      were common. Advanced practice nurses reported good relations with physicians and
      moderate organizational climate but poor relations with administrators and
      limited control over work. Organizational climate had a strong positive
      relationship with psychological ownership. Fostering advanced practice nurse
      psychological ownership could improve job satisfaction and decrease turnover
      leading to increased effectiveness in acute care settings.

PMID- 29357757
TI  - Client reflections on confirmation and disconfirmation of expectations in
      cognitive behavioral therapy for generalized anxiety disorder with and without
      motivational interviewing.
AB  - OBJECTIVE: Addressing methodological shortcomings of prior work on process
      expectations, this study examined client process expectations both prospectively
      and retrospectively following treatment. Differences between clients receiving
      cognitive behavioral therapy (CBT) versus motivational interviewing integrated
      with CBT (MI-CBT) were also examined. METHOD: Grounded theory analysis was used
      to study narratives of 10 participants (N = 5 CBT, 5 MI-CBT) who completed
      treatment for severe generalized anxiety disorder as part of a larger randomized
      controlled trial. RESULTS: Clients in both groups reported and elaborated
      expectancy disconfirmations more than expectancy confirmations. Compared to CBT
      clients, MI-CBT clients reported experiencing greater agency in the treatment
      process than expected (e.g., that they did most of the work) and that therapy
      provided a corrective experience. Despite nearly all clients achieving recovery
      status, CBT clients described therapy as not working in some ways (i.e., tasks
      did not fit, lack of improvement) and that they overcame initial skepticism
      regarding treatment. CONCLUSIONS: Largely converging with MI theory, findings
      highlight the role of key therapist behaviors (e.g., encouraging client autonomy,
      validating) in facilitating client experiences of the self as an agentic
      individual who is actively engaged in the therapy process and capable of
      effecting change.

PMID- 29357758
TI  - Mrs Stone and Dr Smellie: British eighteenth-century birth attendance and long
      run levels and trends in maternal mortality discussed in a north European
      context.
AB  - This is a book review turned research paper. The aim is to estimate the
      differences in the maternal mortality rate (MMR) between untrained midwives,
      expert midwives, and the famous obstetrician Dr Smellie in eighteenth-century
      Britain. The paper shows that the birth attendance practices of the expert
      midwife Mrs Stone and of Dr Smellie were very similar, though Stone used her
      hands whereas Smellie used forceps. Both applied the same invasive techniques to
      successfully deliver women with similar fatal complications, techniques that
      untrained midwives and most surgeons of the time could not perform. However, the
      same procedures, if used for normal births, would have increased the MMR. So, the
      key to the low MMR of both was that they kept interventions away from the
      majority of births that were normal. The paper quantifies the likely MMR for a
      'Stone and Smellie style' birth attendance and concludes that the wider
      dissemination of their techniques can explain the decline in the British MMR.

PMID- 29357759
TI  - Endeavoring to Contextualize Curricula Within an EBP Framework: A Grounded Theory
      Study.
AB  - Adopting evidence-based practice (EBP) principles in undergraduate education can
      facilitate nursing students' appreciation of EBP. Using grounded theory method,
      this study aimed to explore processes used by nurse academics while integrating
      EBP concepts in undergraduate nursing curricula across Australian universities.
      Twenty-three nurse academics were interviewed and nine were observed during
      teaching of undergraduate students. In addition, 20 unit/subject guides were
      analyzed using grounded theory approach of data analysis. The theory " On a path
      to success: Endeavoring to contextualize curricula within an EBP framework"
      reflects academics' endeavors toward linking EBP concepts to practice, aiming to
      contextualize curricula in a manner that engages students within an EBP
      framework. However, academics' journeys were influenced by several contextual
      factors which require strategies to accomplish their endeavors. In conclusion,
      initiatives to minimize barriers, faculty development, and provision of resources
      across educational and clinical settings are fundamental to achieving
      undergraduate curricula underpinned by EBP concepts.

PMID- 29357760
TI  - Do Spanish Medical Students Understand the Concept of Brain Death?
AB  - OBJECTIVE: To analyze the level of understanding of the brain death concept among
      medical students in universities in Spain. METHODS: This cross-sectional
      sociological, interdisciplinary, and multicenter study was performed on 9598
      medical students in Spain. The sample was stratified by geographical area and
      academic year. A previously validated self-reported measure of brain death
      knowledge (questionnaire Proyecto Colaborativo Internacional Donante sobre la
      Donacion y Transplante de Organos) was completed anonymously by students.
      RESULTS: Respondents completed 9275 surveys for a completion rate of 95.7%. Of
      those, 67% (n = 6190) of the respondents understood the brain death concept. Of
      the rest, 28% (n = 2652) did not know what it meant, and the remaining 5% (n =
      433) believed that it did not mean that the patient was dead. The variables
      related to a correct understanding of the concept were: (1) being older ( P <
      .001), (2) studying at a public university ( P < .001), (3) year of medical
      school ( P < .001), (4) studying at one of the universities in the south of Spain
      ( P = .003), (5) having discussed donation and transplantation with the family (
      P < .001), (6) having spoken to friends about the matter ( P < .001), (7) a
      partner's favorable attitude toward donation and transplantation ( P < .001), and
      (8) religious beliefs ( P < .001). CONCLUSIONS: Sixty-seven percent of medical
      students know the concept of brain death, and knowledge improved as they advanced
      in their degree.

PMID- 29357761
TI  - Parental age and offspring mortality: Negative effects of reproductive ageing may
      be counterbalanced by secular increases in longevity.
AB  - As parental ages at birth continue to rise, concerns about the effects of
      fertility postponement on offspring are increasing. Due to reproductive ageing,
      advanced parental ages have been associated with negative health outcomes for
      offspring, including decreased longevity. The literature, however, has neglected
      to examine the potential benefits of being born at a later date. Secular declines
      in mortality mean that later birth cohorts are living longer. We analyse
      mortality over ages 30-74 among 1.9 million Swedish men and women born 1938-60,
      and use a sibling comparison design that accounts for all time-invariant factors
      shared by the siblings. When incorporating cohort improvements in mortality, we
      find that those born to older mothers do not suffer any significant mortality
      disadvantage, and that those born to older fathers have lower mortality. These
      findings are likely to be explained by secular declines in mortality
      counterbalancing the negative effects of reproductive ageing.

PMID- 29357762
TI  - Outcome and selection of revascularization strategy in left main coronary artery
      stenosis.
AB  - OBJECTIVES: To investigate clinical outcome in unselected real-life patients with
      unprotected left main coronary artery (ULMCA) stenosis and determine factors
      associated with selection of revascularization strategy. DESIGN: Consecutive
      patients with ULMCA stenosis at our institution in 2009-2013 (n = 308) were
      retrospectively analyzed with propensity score adjusted Cox proportional hazards
      models for outcome. Baseline characteristics in relation to selection of
      revascularization strategy were analyzed with multivariate logistic regression.
      RESULTS: Patients that underwent PCI (n = 94) had a higher risk of major adverse
      cardiac and cerebrovascular events (MACCE; adjusted HR 2.13 [95% CI 1.08-4.19])
      than patients that had CABG surgery but there was no difference in the
      combination of death and MI (adjusted HR 1.17 [95% CI 0.50-2.75]). Later year of
      index angiography, age, Euroscore II and angiographer favoring PCI was associated
      with PCI as revascularization strategy. Higher SYNTAX score, higher systolic
      blood pressure and angiographer favoring CABG was associated with CABG.
      CONCLUSIONS: In consecutive patients with ULMCA stenosis PCI is associated with
      higher MACCE rates than CABG but there is no difference in death and MI. Later
      year of index angiography, higher age, lower systolic blood pressure, higher
      predicted per-procedural surgical risk, less complex coronary anatomy and
      angiographer favoring PCI increased the probability of revascularization with PCI
      instead of CABG.

PMID- 29357763
TI  - S phase arrest in lymphocytes induced by urinary 1-hydroxypyrene and alcohol
      drinking in coke oven workers.
AB  - Arrest of the cell cycle after DNA damage is believed to promote DNA repair. We
      aim to investigate the main factors affecting cell cycle arrest of lymphocytes in
      coke oven workers. A total of 600 workers were included in this study, and their
      urinary levels of four polycyclic aromatic hydrocarbons (PAH) metabolites, 8
      hydroxydeoxyguanosine (8-OHdG), and cell cycle distribution were determined.
      Urinary PAH metabolites were significantly increased in coke oven workers ( p <
      0.01). It was found that only urinary 2-hydroxynaphthalene and 1-hydroxypyrene
      showed significant positive linear dose-response effects on 8-OHdG in this study
      population ( ptrend = 0.025 and 0.017, respectively). The dose-response effect
      was also observed for smoking and drinking on 8-OHdG ( ptrend < 0.001 and 0.034,
      respectively). Multivariate logistic regression analysis revealed that high
      levels of urinary 1-hydroxypyrene were associated with a significantly increased
      risk of S phase arrest (odds ratio (OR) = 1.32, p = 0.03), so as heavy alcohol
      drinking (OR = 1.31, p = 0.02). Drinking can significantly modify the effects of
      urinary 1-hydroxypyrene on S phase arrest, during co-exposure to both heavy
      drinking and median or high 1-hydroxypyrene levels (OR = 3.31, 95% confidence
      interval (CI) = 1.21-7.63 and OR = 2.56, 95% CI = 1.08-6.06, respectively). Our
      findings demonstrate that coke oven workers with heavy drinking will cause S
      phase arrest so as to repair more serious DNA damage.

PMID- 29357764
TI  - Do emotion regulation, attentional control, and attachment style predict response
      to cognitive behavioral therapy for anxiety disorders? - an investigation in
      clinical settings.
AB  - OBJECTIVE: Approximately, 50% of all individuals with anxiety disorders do not
      benefit from the "gold standard" treatment, namely cognitive behavioral therapy
      (CBT). Reliable predictors of treatment effect are lacking. The primary aim of
      this study was to investigate the predictive value of emotion regulation,
      attentional control, and attachment style for group-based CBT outcomes in routine
      clinical settings. METHOD: A total of 76 patients with anxiety disorders received
      manual-based group CBT at psychiatric outpatient clinics. Emotion regulation,
      attachment style, and attentional control were assessed with self-report measures
      and with an experimental computer-based attentional control task at baseline. The
      severity of anxiety was assessed at intake, post-treatment, and at a 6-month
      follow-up. RESULTS: Attentional control, emotion regulation, and attachment
      avoidance did not predict treatment outcomes. Higher attachment anxiety at
      baseline was significantly related to poorer outcome. CONCLUSION: In routine
      clinical settings, high attachment anxiety may predict poorer outcomes for group
      based CBT.

PMID- 29357765
TI  - Accessible miRNAs as Novel Toxicity Biomarkers.
AB  - Novel tissue injury biomarkers have recently been identified that outperform or
      add value to the conventional safety biomarkers. These novel biomarkers have
      enhanced sensitivity and/or specificity in monitoring drug-induced tissue injury
      in a variety of tissues, included liver, kidney, and skeletal muscle. Among these
      novel biomarkers, microRNAs (miRNAs) are one type in particular that have
      received much attention in recent years. These microRNAs are short, endogenous
      noncoding nucleic acids that are involved in modulation and regulation of mRNA
      transcripts. Other attributes of miRNAs are that they exist in tissues at high
      abundance, and individual miRNAs can be highly tissue-specific. These miRNAs can
      be readily assayed in blood, urine, or cerebral spinal fluid, making them
      attractive as accessible biomarkers of tissue injury. Further, the miRNA
      processing involves embedding the miRNA within a protein complex, making them
      stable in plasma upon leakage from injured tissues. This review article will
      highlight the discovery of tissue-specific miRNAs and their evolution as novel
      toxicity biomarkers in recent years.

PMID- 29357767
TI  - Letter to the editor regarding 'Percutaneous laser disc decompression versus
      conventional microdiscectomy for patients with sciatica: Two-year results of a
      randomised controlled trial'.

PMID- 29357766
TI  - A Toxicological Assessment of Creatyl-l-Leucine.
AB  - A battery of toxicological studies was conducted to investigate the genotoxicity
      and repeated-dose oral toxicity of creatyl-l-leucine, a synthetic compound, in
      rats in accordance with internationally accepted guidelines. There was no
      evidence of mutagenicity in a bacterial reverse mutation test and in an in vitro
      mammalian chromosomal aberration test. There was no genotoxic activity observed
      in an in vivo mammalian micronucleus test at concentrations up to the limit dose
      of 2,000 mg/kg bw/d. Creatyl-l-leucine did not cause mortality or toxic effects
      in Hsd.Han Wistar rats in a 90-day repeated-dose oral (gavage) toxicity study at
      doses of 1,250, 2,500, and 5,000 mg/kg bw/d. The no observed adverse effect level
      from the 90-day study was determined to be 5,000 mg/kg bw/d, the highest dose
      tested, for both male and female rats.

PMID- 29357768
TI  - Ruptured dissecting aneurysm in communicating internal carotid artery segments
      treated using a stent-assisted endovascular technique.
AB  - Hemorrhagic intracranial dissecting aneurysms are known to have a poor natural
      history and an increased tendency to rebleed. The communicating segment of the
      internal carotid artery (ICA) is an infrequent site of dissection that is
      difficult to manage using deconstructive endovascular treatment because of the
      need to preserve important vascular branches. We report two cases of ruptured
      dissecting aneurysms that occurred in communicating segments of the ICA and
      treated using a reconstructive endovascular technique involving stent-assisted
      coiling. Case 1 was a 59-year-old woman who was diagnosed with subarachnoid
      hemorrhage (SAH). Digital subtraction angiography (DSA) indicated a ruptured
      dissecting aneurysm that arose from the left communicating segment of the ICA.
      Stent-assisted coiling was performed and followed by a second overlapping stent
      technique. No deterioration was observed on DSA after one week of follow-up or on
      magnetic resonance angiography (MRA) after four months of follow-up. The patient
      was discharged without neurological complications (Glasgow Outcome Scale 5). Case
      2 was a 34-year-old man who was admitted with a diagnosis of SAH. DSA revealed a
      suspected lesion of a ruptured dissecting aneurysm of the left communicating
      segment of the ICA. Stent-assisted coiling was performed, and partial occlusion
      was achieved. No deterioration was observed on DSA after two weeks of follow-up
      or on MRA after six months of follow-up. The patient was discharged without
      neurological complications (Glasgow Outcome Scale 5). These cases suggest that
      using stent-assisted coiling could be a feasible modality for treating ruptured
      ICA dissecting aneurysms in the communicating segment.

PMID- 29357769
TI  - Is the body composition development in premature infants associated with a
      distinctive nuclear magnetic resonance metabolomic profiling of urine?
AB  - OBJECTIVE: Preterm infants' body composition at term-corrected age differs from
      that of term infants but appears to be similar at the age of 3 months. The aim of
      this study was to compare the metabolomic pattern of preterm infants at term and
      at 3 months with that of term infants and to determine its association with body
      composition development. METHOD: We designed a pilot study. Growth and body
      composition were evaluated by an air displacement plethysmography system in 13
      preterm infants and seven term newborns at term and at 3 months of corrected age.
      Urine samples were collected at the same time points and analysed by nuclear
      magnetic resonance. RESULTS: At term-corrected age, preterm infants showed a
      higher fat mass percentage compared with that of term newborns, whereas at 3
      months of corrected age, the body composition parameters were similar between the
      groups. At the first time point, nuclear magnetic resonance analysis showed a
      urinary increase in choline/phosphocholine, betaine and glucose in preterm
      infants. At the second time point, the preterm group exhibited a urinary increase
      in choline/phosphocholine and a decrease in betaine. CONCLUSIONS: The increased
      urinary excretion of choline, a betaine precursor, could reflect a potential
      altered metabolism in preterm infants.

PMID- 29357770
TI  - Immunologic and Virologic Outcomes of Obese and Nonobese Incarcerated Adults on
      Antiretroviral Therapy for HIV Infection.
AB  - BACKGROUND: Obesity is common among patients with HIV. The objective of this
      study was to characterize response to antiretroviral therapy (ART) in a cohort of
      obese incarcerated adults compared to a nonobese cohort. METHODS: A retrospective
      matched cohort study was conducted in an HIV telemedicine clinic. Patients with
      body mass index (BMI) >30 kg/m2 who received the same ART with >95% adherence for
      at least 6 months were matched to nonobese patients by age, gender, ART, CD4
      count, and viral load at baseline. RESULTS: Twenty pairs were included, with an
      average BMI of 24 kg/m2 in the nonobese cohort and 35 kg/m2 in the obese cohort.
      No difference was observed in the proportion of patients who achieved virologic
      suppression or the change in CD4 count from baseline to 6 to 12 months.
      CONCLUSION: This study revealed no differences in immunologic recovery or
      virologic suppression between obese and nonobese patients in an adult
      correctional population.

PMID- 29357771
TI  - Prevalence of Non-AIDS Comorbidities and Factors Associated with Metabolic
      Complications among HIV-Infected Patients at a Thai Referral Hospital.
AB  - OBJECTIVES: The prevalence of non-AIDS-related comorbidities is increasing in HIV
      infected patients receiving antiretroviral therapy. In Thailand, data regarding
      the prevalence of non-AIDS comorbidities and factors associated with metabolic
      complications in HIV-infected patients have not been well-documented. METHODS:
      This cross-sectional study was conducted in 2011 and included 874 HIV-infected
      patients. RESULTS: The age of patients was 45(8) years represented as mean
      (standard deviation [SD]). The current CD4 count was 502(247) cells/mm3. In all,
      388 (44%) of the included patients had at least 1non-AIDS comorbidity. The most
      frequently documented comorbidities were hyperlipidemia in 271 (70%) patients.
      Using multivariate analysis, older age(odds ratio [OR] = 1.82, 95% confidence
      interval [CI] = 1.51-2.19), male sex (OR = 1.55, 95%CI = 1.14-2.11), high current
      CD4 count(OR = 1.00, 95%CI = 1.00-1.00), and taking abacavir (ABC)-containing(OR
      = 2.59, 95%CI = 1.16-5.78)and didanosine (ddI)-containing antiretroviral regimens
      (OR = 4.16, 95%CI = 1.09-15.84)were associated with the presence of metabolic
      complications (all Ps<.05). CONCLUSION: The prevalence of comorbidities is
      substantially high. Clinical monitoring and effective management of these
      comorbidities and metabolic complications are recommended, especially in HIV
      infected patients who present with these associated factors.

PMID- 29357772
TI  - HIV RNA Suppression during and after Pregnancy among Women in the HIV Outpatient
      Study, 1996 to 2015.
AB  - OBJECTIVE: To examine HIV viral suppression during/after pregnancy. DESIGN:
      Prospective observational cohort. METHODS: We identified pregnancies from 1996 to
      2015. We examined HIV RNA viral load (VL), VL suppression (<=500 copies/mL), and
      antiretroviral therapy (ART) status at pregnancy start, end, and 6 months
      postpartum. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) for
      VL nonsuppression. RESULTS: Among 253 pregnancies analyzed, 34.8% of women
      exhibited VL suppression at pregnancy start, 60.1% at pregnancy end, and 42.7% at
      6 months postpartum. Median VL (log10 copies/mL) was 2.80 (interquartile range
      [IQR]: 1.40-3.85) at pregnancy start, 1.70 (IQR: 1.40-2.82) at pregnancy end, and
      2.30 (IQR: 1.40-3.86) at postpartum. Risk of postpartum VL nonsuppression was
      also lower among women on ART and with VL suppression at pregnancy end (versus
      those not; adjusted RR = 0.30, 95% CI: 0.17-0.53). CONCLUSIONS: Maintaining VL
      suppression among US women remains a challenge, particularly during postpartum.
      Achieving VL suppression earlier during pregnancy benefits women subsequently.

PMID- 29357773
TI  - Total knee arthroplasty in a knee with triple deformity of femur-tibia-extensor
      mechanism.
AB  - By analyzing a case of total knee arthroplasty (TKA) in a knee with complex
      deformity and secondary osteoarthritis, we demonstrated the rationale of
      preoperative planning and the detail of intraoperative execution. The lady had
      right TKA with combined medial closing wedge femoral osteotomy, neutral wedge
      valgus derotational tibial osteotomy, fibular osteotomy, and quadriceplasty. Four
      months later, she had left TKA. Osteotomies healed well and she was pain-free at
      18 months after right TKA. Combination of intra-articular and extra-articular
      correction of deformity was the key to achieve a well-aligned TKA with good soft
      tissue balancing in both coronal and sagittal planes. The choice of osteotomy
      fixation method should follow the principles of bone healing. Fibular osteotomy
      should have been made at the level of tibial osteotomy with caution. Use of
      appropriate TKA prosthesis could have enhanced the osteotomy fixation while
      decreasing the complication.

PMID- 29357774
TI  - Acceleration of the healing process of full-thickness wounds using hydrophilic
      chitosan-silica hybrid sponge in a porcine model.
AB  - In this study, we evaluated the surface characterization of a novel chitosan
      silica hybridized membrane and highlighted the substantial role of silica in the
      wound environment. The chemical coupling of chitosan and silica resulted in a
      more condensed network compared with pure chitosan, which was eventually able to
      stably maintain its framework, particularly in the wet state. In addition, we
      closely observed the wound-healing process along with the surface interaction
      between chitosan-silica and the wound site using large-surface-area wounds in a
      porcine model. Our evidence indicates that chitosan-silica exerts a synergetic
      effect of both materials to promote a remarkable wound-healing process. In
      particular, the silica in chitosan-silica accelerated wound closure including
      wound contraction, and re-epithelialization via enhancement of cell recruitment,
      epidermal maturity, neovascularization, and granulation tissue formation compared
      with pure chitosan and other commercial dressing materials. This advanced wound
      dressing material may lead to effective treatment for problematic cutaneous
      wounds and can be further applied for human skin regeneration.

PMID- 29357775
TI  - Calcium carbonate end-capped, folate-mediated Fe3O4@mSiO2 core-shell nanocarriers
      as targeted controlled-release drug delivery system.
AB  - Magnetic mesoporous silica nanospheres (MMSN) were prepared and the surface was
      modified with cancer cell-specific ligand folic acid. Calcium carbonate was then
      employed as acid-activated gatekeepers to cap the mesopores of the MMSN, namely,
      MMSN-FA-CaCO3. The formation of the MMSN-FA-CaCO3 was proved by several
      characterization techniques, viz. transmission electron microscopy, zeta
      potential measurement, Fourier transform infrared spectroscopy, BET surface area
      measurement, and UV-Vis spectroscopy. Daunomycin was successfully loaded in the
      MMSN-FA-CaCO3 and the system exhibited sensitive pH stimuli-responsive release
      characteristics under blood or tumor microenvironment. Cellular uptake by folate
      receptor (FR)-overexpressing HeLa cells of the MMSN-FA-CaCO3 was higher than that
      by non-folated-conjugated ones. Intracellular-uptake studies revealed
      preferential uptake of these nanoparticles into FR-positive [FR(+)] HeLa than FR
      negative [FR(-)]A549 cell lines. DAPI stain experiment showed high apoptotic rate
      of MMSN-FA-DNM-CaCO3 to HeLa cells. The present data suggest that the CaCO3
      coating and folic acid modification of MMSN are able to create a targeted, pH
      sensitive template for drug delivery system with application in cancer therapy.

PMID- 29357776
TI  - Comparison of Lurasidone Versus Quetiapine for the Treatment of Delirium in
      Critically Ill Patients.
AB  - OBJECTIVE: To evaluate the efficacy and safety of lurasidone compared with
      quetiapine for treatment of delirium in critically ill patients. DESIGN:
      Prospective, observational cohort study. SETTING: Single-center community
      teaching hospital. PATIENTS: Forty adult intensive care unit (ICU) patients with
      delirium (Confusion Assessment Method in the ICU positive), tolerating enteral
      nutrition, and without active alcohol withdrawal or prior use of atypical
      antipsychotics. INTERVENTIONS: Patients were treated at the discretion of the
      prescriber with either lurasidone or quetiapine for delirium. Dose escalation
      and/or discontinuation were determined at the discretion of individual providers.
      RESULTS: Baseline characteristics differed with a higher severity of illness in
      patients in the quetiapine group (n = 20) and a higher baseline QTc interval in
      the lurasidone group (n = 20). No significant difference was seen in the time to
      delirium resolution (3.2 vs 3.4 days), average daily haloperidol requirements
      (5.7 vs 6.9 mg), hospital length of stay (LOS; 23.6 vs 27.9 days), or ICU LOS
      (12.1 vs 14.2 days). Lurasidone was associated with fewer ventilator support days
      (4.0 [interquartile range, IQR: 2.3-6.8] days vs 7 [IQR: 4.0-9.8; P = .0295]
      days) but also a fewer number of delirium-free days (0 [IQR: 0-1.0] days vs 2
      [IQR: 0-3.0; P = .0231] days). Additionally, no difference was seen for ICU
      mortality (20% vs 20%), percentage of time oversedated (2.8% vs 2.7%), or
      incidence of QTc prolongation (10.0% vs 10.0%). CONCLUSIONS: Lurasidone for the
      treatment of delirium in critically ill patients did not differ in the time to
      delirium resolution when compared to quetiapine. Additionally, the incidence of
      QTc prolongation between agents does not appear to be different. Future
      randomized trials should evaluate dose escalation schemes and a larger proportion
      of patients to evaluate differences in mortality, efficacy, and life-threatening
      arrhythmias associated with atypical antipsychotic use.

PMID- 29357777
TI  - Outcomes and Costs of Patients Admitted to the Intensive Care Unit Due to
      Accidental or Intentional Poisoning.
AB  - INTRODUCTION: Acute poisoning represents a major cause of morbidity and
      mortality, and many of these patients are admitted to the intensive care unit
      (ICU). However, little is known regarding ICU costs of acute poisoning. METHODS:
      This was a retrospective matched database analysis of patients admitted to the
      ICU with acute poisoning from 2011 to 2014. It was performed in 2 ICUs within a
      single tertiary care hospital system. All patient information, outcomes, and
      costs were stored in the hospital data warehouse. Control patients were defined
      as randomly selected age-, sex-, severity index-, and comorbidity index-matched
      nonpoisoned ICU patients (1:4 matching ratio). RESULTS: A total of 8452
      critically ill patients were admitted during the study period, of whom 277 had a
      diagnosis of acute poisoning. The mean age was 44.5 years, and the most common
      xenobiotics implicated were sedative hypnotics (20.2%), antidepressants (15.2%),
      and opioids (10.5%). Of these, 73.6% of poisonings were deemed intentional. In
      hospital mortality of poisoned patients was 5.1%, compared to 11.1% for control
      patients ( P < .01). The median ICU length of stay (LOS) for poisoned patients
      was 3.0 days, compared with 4.0 days for control patients ( P < .01). The mean
      total cost for poisoned patients was CAD$18 958. Control patients had a
      significantly higher mean total cost of CAD$60 628 ( P < .01). The xenobiotics
      associated with the highest costs were acetaminophen (CAD$18 585), toxic alcohols
      (CAD$16 771), and opioids (CAD$12 967). CONCLUSIONS: In our cohort, we confirmed
      the long-held belief that patients admitted to the ICU with a primary diagnosis
      of poisoning have a lower mortality rate, ICU LOS, and overall cost per ICU
      admission than nonpoisoned patients. However, poisoned patients still accrue
      significant daily costs, with the highest costs attributed to xenobiotics with
      known antidotes, such as acetaminophen, toxic alcohols, and opioids.

PMID- 29357778
TI  - Normal Baseline Function Is Associated With Delayed Rehabilitation in Critically
      Ill Children.
AB  - BACKGROUND: Early mobilization of patients in the adult intensive care unit (ICU)
      is associated with improved functional outcomes and shorter ICU stay. Although
      emerging evidence suggests that early mobilization in pediatric ICUs (PICUs) is
      safe and feasible, physical therapist (PT) consultation may be delayed because of
      perceptions that patient acuity precludes mobilization activities. Factors that
      influence timely involvement of PTs to facilitate acute rehabilitation in
      critically ill children have not been characterized. The aim of this study was to
      identify patient-level factors for early PT consultation in a tertiary care PICU
      before large-scale implementation of a multicomponent early mobilization program.
      METHODS: We conducted a retrospective analysis of data from the PICU Up! Quality
      Improvement Initiative. The primary outcome was early rehabilitation, defined as
      PT consultation within the first 3 days of PICU admission. Patients (n = 100)
      were divided into 2 groups by outcome, and predictive factors for early
      rehabilitation were analyzed with logistic regression. RESULTS: Of 100 children,
      54% received early rehabilitation. In univariate analyses, higher pediatric risk
      of mortality (PRISM) score ( P < .001), baseline motor impairment ( P < .01),
      developmental delay ( P = .04), mechanical ventilation ( P = .1), and number of
      devices ( P = .01) were associated with early rehabilitation. In a logistic
      regression model, predictive factors for early rehabilitation included baseline
      motor impairment (adjusted odds ratio = 5.36, 95% confidence interval [CI] = 1.3
      22.0) and higher PRISM score (adjusted odds ratio = 1.17, 95% CI = 1.02-1.34).
      CONCLUSIONS: Critically ill children with normal baseline function or lower
      acuity of illness are less likely to have initiation of early rehabilitation with
      PT prior to implementation of a unit-wide early mobilization program. Baseline
      motor impairment and higher PRISM scores were independently associated with early
      rehabilitation. These findings highlight the need for streamlined criteria for PT
      consultation to meet the rehabilitation needs of all critically ill patients.

PMID- 29357779
TI  - Adversity and Resilience Are Associated with Outcome after Mild Traumatic Brain
      Injury in Military Service Members.
AB  - The objective of this study was to assess the associations between resilience,
      adversity, post-concussion symptoms, and post-traumatic stress symptom reporting
      after mild traumatic brain injury (mTBI). We hypothesized that resilience would
      be associated with less symptom reporting, and adversity would be associated with
      greater symptom reporting. This was a cross-sectional study of retrospective data
      collected for an ongoing TBI repository. United States military service members
      who screened positive for mTBI during a primary care visit completed the Trauma
      History Screen (THS), Connor-Davidson Resilience Scale (CD-RISC), Neurobehavioral
      Symptom Inventory (NSI), and post-traumatic stress disorder (PTSD) Checklist
      Civilian Version (PCL-C). Data collected from February 2015 to August 2016 were
      used for the present study. Only participants with complete data for the above
      measures were included, yielding a sample size of 165 participants. Adversity
      (THS) and resilience (CD-RISC) scores were each correlated significantly with
      post-concussion (NSI) and traumatic stress (PCL-C) total and subscale scores in
      the hypothesized direction. Interactions between adversity and resilience were
      absent for all measures except the NSI sensory subscale. Four traumatic event
      types were significantly associated positively with most NSI and PCL-C total and
      subscale scores, but the age at which traumatic events were first experienced
      showed few and mixed significant associations. In conclusion, resilience and
      adversity were significantly associated with symptom endorsement after mTBI.
      Screening for cumulative adversity may identify individuals at greater risk of
      developing persistent post-concussion symptoms and/or PTSD, and interventions
      that increase resilience may reduce symptom severity.

PMID- 29357780
TI  - Crizotinib-induced erosive esophagitis in a pediatric patient with neuroblastoma.
AB  - Crizotinib is an oral tyrosine kinase inhibitor, approved by the FDA in 2011, for
      use in anaplastic lymphoma kinase positive, metastatic, non-small cell lung
      cancer. Crizotinib inhibits oncogenic protein expression and impairs cellular
      proliferation in tumors with an overexpressed anaplastic lymphoma kinase gene.
      Currently used most frequently in the adult patient population, pediatric use is
      becoming more prominent, specifically in disease states exhibiting anaplastic
      lymphoma kinase-positive, metastatic disease, such as neuroblastoma.
      Approximately 8% of neuroblastomas have activating anaplastic lymphoma kinase
      mutations, making this a promising target for a difficult-to-treat disease.
      Studies in the pediatric population are limited. However, targeted anaplastic
      lymphoma kinase-inhibitor therapies have shown improved outcomes at both one-year
      and two-year marks in both overall survival and progression free survival in
      anaplastic lymphoma kinase-positive adult patients with non-small cell lung
      cancer. One Children's Oncology Group phase I trial examined toxicities
      associated with anaplastic lymphoma kinase inhibitor therapy in pediatric
      patients. Results revealed varying grades in severity of neutropenia, dizziness,
      and liver function test elevation. In the adult population, severe toxicities
      reported by the manufacturer include effects on liver, cardiac and lung function.
      Additionally, several cases of severe, erosive, pill-esophagitis due to
      crizotinib therapy have been documented in the adult population. Erosive
      esophagitis is common in the pediatric population due to a variety of factors.
      Ingestion of medications or other corrosive agents accounts for approximately 3
      5% (5000-10,000 cases per year) of esophagitis presentation in the pediatric
      population. Common causative medications include non-steroidal anti-inflammatory
      drugs, antibiotics such as doxycycline and tetracycline, and ferrous sulfate.
      Presented here is the first reported case of crizotinib-induced pill esophagitis
      in a pediatric patient.

PMID- 29357781
TI  - Dynamic dosing of romiplostim in patients with immune thrombocytopenia purpura:
      Two case reports.
AB  - Romiplostim is a thrombopoietin receptor agonist approved for the treatment of
      immune thrombocytopenia purpura. When following FDA-approved romiplostim
      prescribing recommendations to withhold treatment for platelet counts above
      400k/uL, some patients exhibit a precipitous decline in their platelet count
      potentially causing patient harm. We present two cases where stable platelet
      counts were achieved only through persistent weekly dosing of romiplostim despite
      platelet counts above 400k/uL on the day of administration. Therefore, continuous
      weekly dosing of romiplostim despite platelet count being above 400k/uL combined
      with twice weekly vigilant monitoring is an alternative method of romiplostim
      dosing that mitigates severe fluctuations in platelets. We also discuss important
      details, postulated mechanisms, and evidence-based mitigation strategies.

PMID- 29357782
TI  - Aplastic anemia secondary to propylthiouracil: A rare and life-threatening
      adverse effect.
AB  - Background Propylthiouracil has been in use for more than half a century for the
      treatment of hyperthyroidism. While it is largely known to cause agranulocytosis,
      its association with aplastic anemia is rarely heard of. Our case will be the
      third in literature to suggest aplastic anemia as a manifestation of
      propylthiouracil, which unfortunately culminated in the death of the patient.
      Case A 67-year-old female, with recently diagnosed metastatic adenocarcinoma of
      the lung, developed hyperthyroidism after being started on Nivolumab and
      Iplimumab. After she developed atrial fibrillation, she was started on
      propylthiouracil to control the thyroid activity. Soon after that, she was
      admitted with severe neutropenia, which progressed to pancytopenia confirmed as
      aplastic anemia on a bone marrow biopsy. Despite discontinuation of
      propylthiouracil and aggressive treatment, she developed septic shock and multi
      organ failure, leading to her death. Conclusion Aplastic anemia has been
      sparingly reported as an extremely rare complication of propylthiouracil. Further
      adding to the ambiguity is the unknown etiology and lack of specific therapy for
      the complication when attributed to propylthiouracil. The disease can carry an
      extremely poor prognosis if untreated, as proven by our case. Due to the same
      reasons, we recommend that further investigations be done to elucidate the
      pathogenesis and assist with treatment of the disease when caused by
      propylthiouracil.

PMID- 29357783
TI  - The ever-changing engram: towards an integrated understanding of long-term memory
      dynamics.

PMID- 29357784
TI  - Outcome and Safety of Radical Resection in Non-Small Cell Lung Cancer Patients
      via Glasses-Free 3-Dimensional Video-Assisted Thoracoscope Versus 2-Dimensional
      Video-Assisted Thoracoscope.
AB  - OBJECTIVES: The investigation was aimed to evaluate the safety and efficacy of
      glasses-free 3-dimensional (3D) video-assisted thoracoscopic surgery (VATS)
      versus 2D VATS for radical resection of non-small cell lung cancer (NSCLC).
      METHODS: We reviewed the clinical data of patients with pathologically proven
      NSCLC who underwent glasses-free 3D (the 3D group) and 2D VATS radical lobectomy
      (the 2D group) with systematic lymph node dissection. The outcomes of this study
      included operative characteristics and safety of 2D and 3D VATS, and duration of
      lymphadenectomy of right stations 2 and 4. RESULTS: A total of 190 patients were
      eligible for the study. The 2D group consisted of 108 patients while the 3D group
      included 82 patients. The 2 groups were comparable in demographic and baseline
      variables ( P > .05). The median number of resected lymph nodes was 19 in both
      groups ( P = .583). The median length of hospital stay was comparable between the
      2 groups (2D, 7 days vs 3D, 8 days; P = .167). No operative mortality was
      reported in either group. Complications developed in 21 (19.4%) patients in the
      2D group and 14 (17.1%) in the 3D group ( P = .710). A subgroup analysis of
      patients who underwent right station 2 and 4 lymphadenectomy showed that the mean
      time for right station 2 and 4 lymph node dissection was significantly shorter in
      the 3D group than in the 2D group (3D, 430.9 +/- 237.2 vs 2D, 648.6 +/- 364.1
      seconds; P < .001). CONCLUSIONS: Glasses-free 3D VATS and 2D VATS are comparable
      in operative characteristics and safety profile for radical resection of NSCLC.
      Glasses-free 3D visualization facilitates more rapid right-sided mediastinal
      lymphadenectomy.

PMID- 29357785
TI  - Safety, Efficacy, and Timeliness of Intravenous Potassium Chloride Replacement
      Protocols in a Pediatric Cardiothoracic Intensive Care Unit.
AB  - OBJECTIVE: Hypokalemia in children following cardiac surgery occurs frequently,
      placing them at risk of life-threatening arrhythmias. However, renal
      insufficiency after cardiopulmonary bypass warrants careful administration of
      potassium (K+). Two different nurse-driven protocols (high dose and tiered
      dosing) were implemented to identify an optimal K+ replacement regimen, compared
      to an historical low-dose protocol. Our objective was to evaluate the safety,
      efficacy, and timeliness of these protocols. DESIGN: A retrospective cohort
      review of pediatric patients placed on intravenous K+ replacement protocols over
      1 year was used to determine efficacy and safety of the protocols. A prospective
      single-blinded review of K+ repletion was used to determine timeliness. PATIENTS:
      Pediatric patients with congenital or acquired cardiac disease. SETTING: Twenty
      four-bed cardiothoracic intensive care unit in a tertiary children's hospital.
      INTERVENTIONS: Efficacy was defined as fewer supplemental potassium chloride
      (KCl) doses, as well as a higher protocol to total doses ratio per patient.
      Safety was defined as a lower percentage of serum K+ levels >=4.8 mEq/L after a
      dose of KCl. Between-group differences were assessed by nonparametric univariate
      analysis. RESULTS: There were 138 patients with a median age of 3.0
      (interquartile range: 0.23-10.0) months. The incidence of K+ levels >=4.8 mEq/L
      after a protocol dose was higher in the high-dose protocol versus the tiered
      dosing protocol but not different between the low-dose and tiered-dosing
      protocols (high dose = 2.2% vs tiered dosing = 0.5%, P = .05). The ratio of
      protocol doses to total doses per patient was lower in the low-dose protocol
      compared to the tiered-dosing protocol ( P < .05). Protocol doses were
      administered 45 minutes faster ( P < .001). CONCLUSION: The tiered-dosed, nurse
      driven K+ replacement protocol was associated with decreased supplemental K+
      doses without increased risk of hyperkalemia, administering doses faster than
      individually ordered doses; the protocol was effective, safe, and timely in the
      treatment of hypokalemia in pediatric patients after cardiac surgery.

PMID- 29357786
TI  - Cultural Aspects of End-of-Life Care Planning for African Americans: An
      Integrative Review of Literature.
AB  - Advance directive completion rates among the general population are low. Studies
      report even lower completion rates among African Americans are affected by
      demographic variables, cultural distinctives related to patient autonomy,
      mistrust of the health care system, low health literacy, strong spiritual
      beliefs, desire for aggressive interventions, importance of family-communal
      decision making, and presence of comorbidities. An integrative review was
      conducted to synthesize nursing knowledge regarding cultural perspectives of end
      of-life and advance care planning among African Americans. Twenty-four articles
      were reviewed. Nurses educate patients and families about end-of-life planning as
      mandated by the Patient Self-Determination Act of 1991. Implementation of advance
      directives promote patient and family centered care, and should be encouraged.
      Clinicians must be sensitive and respectful of values and practices of patients
      of diverse cultures, and initiate conversations with open-ended questions
      facilitating patient trust and sharing within the context of complex beliefs,
      traditions, and lifeways.

PMID- 29357788
TI  - Recent Advances in the Development of Antimicrobial Peptides (AMPs): Attempts for
      Sustainable Medicine?
AB  - BACKGROUND: Since the first isolation of antimicrobial peptides (AMPs) they have
      attracted extensive interest in medicinal chemistry. However, only a few AMP
      based drugs are currently available on the market. Despite their effectiveness,
      biodegradability, and versatile mode of action that is less likely to induce
      resistance compared to conventional antibiotics, AMPs suffer from major issues
      that need to be addressed to broaden their use. Notably, AMPs can lack
      selectivity leading to side effects and cytotoxicity, and also exhibit in vivo
      instability. Several strategies are being actively considered to overcome the
      limitations that restrain the success of AMPs. METHODS: In the current work,
      recent strategies reported for improving AMPs in the context of drug design and
      delivery were surveyed, and also their possible impact on patients and the
      environment was assessed. RESULTS: As a major advantage AMPs possess an easily
      tunable skeleton offering opportunities to improve their properties. Strategic
      structural modifications and the beneficial properties of cyclic or branched AMPs
      in term of stability have been reported. The conjugation of AMPs with
      nanoparticles has also been explored to increase their in vivo stability. Other
      techniques such as the coupling of AMPs with specific antibodies aim to increase
      the selectivity of the potential drug towards the target. These strategies were
      evaluated for their effect on the environment highlighting green technologies.
      CONCLUSION: Although further research is needed taking into account both
      environmental and human health consequences of novel AMPs, several of these
      compounds are promising drug candidates for use in sustainable medicine.

PMID- 29357787
TI  - Knockdown of Annexin A1 Enhances Radioresistance and Inhibits Apoptosis in
      Nasopharyngeal Carcinoma.
AB  - Radiotherapy is the primary treatment for nasopharyngeal carcinoma while
      radioresistance can hinder efficient treatment. To explore the role of annexin A1
      and its potential mechanisms in radioresistance of nasopharyngeal carcinoma,
      human nasopharyngeal carcinoma cell line CNE2-sh annexin A1 (knockdown of annexin
      A1) and the control cell line CNE2-pLKO.1 were constituted and CNE2-sh annexin A1
      xenograft mouse model was generated. The effect of annexin A1 knockdown on the
      growth of xenograft tumor after irradiation and radiation-induced DNA damage and
      repair was analyzed. The results of immunohistochemistry assays and Western
      blotting showed that the level of annexin A1 was significantly downregulated in
      the radioresistant nasopharyngeal carcinoma tissues or cell line compared to the
      radiosensitive nasopharyngeal carcinoma tissues or cell line. Knockdown of
      annexin A1 significantly promoted CNE2-sh annexin A1 xenograft tumor growth
      compared to the control groups after irradiation. Moreover, the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling assays revealed that
      knockdown of annexin A1 significantly inhibited apoptosis in vivo compared to the
      control groups. We assessed the intracellular reactive oxygen species levels and
      the extent of radiation-induced DNA damage and repair using reactive oxygen
      species assay, comet assays, and immunohistochemistry assay. The results showed
      that knockdown of annexin A1 remarkedly reduced the intracellular reactive oxygen
      species levels, level of DNA double-strand breaks, and the phosphorylation level
      of H2AX and increased the accumulation of DNA-dependent protein kinase in
      nasopharyngeal carcinoma cells after irradiation. The findings suggest that
      knockdown of annexin A1 inhibits DNA damage via decreasing the generation of
      intracellular reactive oxygen species and the formation of gamma-H2AX and
      promotes DNA repair via increasing DNA-dependent protein kinase activity and
      therefore improves the radioresistance in nasopharyngeal carcinoma cells.
      Together, our findings suggest that knockdown of annexin A1 promotes
      radioresistance in nasopharyngeal carcinoma and provides insights into
      therapeutic targets for nasopharyngeal carcinoma radiotherapy.

PMID- 29357789
TI  - Current State of In vitro Cell-Based Renal Models.
AB  - BACKGROUND: Renal proximal tubule (PT) epithelial cells, expressing uptake and
      efflux transporters at basolateral and apical membranes, are the location of
      active renal drug secretion and reabsorption. In addition to singly transfected
      cells, an in vitro renal cell-based model is a requirement to study the active
      renal secretion of drugs, drug-drug interactions (DDIs), drug-induced kidney
      injury, nephrotoxicity holistically and potentially renal replacement therapies.
      OBJECTIVES: So far, two-dimensional (2D) cell culture of primary and immortalized
      PT cells has been the only tool to study drugs active secretion, interactions and
      nephrotoxicity, however a number of in vivo characteristics of cells such as drug
      transporter expression and function, along with morphological features are lost
      during in vitro cell culture. Cellular microenvironment, extracellular matrix,
      cell-cell interactions, microfluidic environment and tubular architecture are the
      factors lacking in 2D cell culture. Currently, there are a few 3D cell culture
      platforms mimicking the in vivo conditions of PT cells and thus potentially
      enabling the necessary factors for the full functional PT cells. CONCLUSION: In
      this review, we address in vivo physiological and morphological characteristics
      of PT cells, comparing their available sources and remaining in vivo features. In
      addition, 2D and 3D cell culture platforms and the influence of cell culture
      architecture on the physiological characteristics of cells are reviewed. Finally,
      future perspective of 3D models, kidney and multi organs on a chip, generation of
      kidney organoids, other ex vivo renal models and their capabilities to study drug
      disposition and in vitro-in vivo extrapolation are described.

PMID- 29357790
TI  - A New Era for Hemoglobinopathies: More Than One Curative Option.
AB  - Hemoglobinopathies, including severe beta-thalassemia and sickle cell disease,
      represent the most common monogenic disorders worldwide. Allogeneic hematopoietic
      stem cell transplantation (allo-HCT) is the only approved curative option for
      these syndromes, albeit limited to patients having a suitable donor. Gene
      therapy, by making use of the patient's own hematopoietic stem cells to introduce
      a normal copy of the beta-globin gene by viral vectors, bridged the gap between
      the need for cure of patients with hemoglobinopathies and the lack of a donor,
      without incurring the immunological risks of allo-HSCT. However, gene therapy for
      hemoglobinopathies proved a difficult and elusive goal for decades and only
      recently, lenti-viral vector gene therapy was successfully transferred to the
      clinic. Importantly, during the last years, additional curative options for
      patients with thalassemia and sickle cell disease are being developed, based on
      the ability to manipulate the genome by employing programmable nucleases and next
      generation genome-modifying tools, thus providing the exciting prospects of
      targeted in-situ gene correction. In this review, we will summarize current
      developments in the new era of treatment for hemoglobinopathies, elaborate on
      lessons gained from gene therapy trials and discuss the exciting prospects and
      challenges of genome editing.

PMID- 29357791
TI  - Neurodegenerative Disorders Treatment: The MicroRNA Role.
AB  - Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease,
      amyotrophic lateral sclerosis, Huntington's disease and prion disease are not
      timely and effectively treated using conventional therapies. This emphasizes the
      need for alternative therapeutic approaches. In this respect, gene-based
      therapies have been adopted as potentially feasible alternative therapies, where
      the microRNA (miRNA) approach has experienced a great explosion in recent years.
      Because miRNAs have been shown to be implicated in the pathogenesis of several
      diseases including neurodegenerative diseases, they are intensely studied as
      candidates for diagnostic and prognostic biomarkers, as predictors of drug
      response and as therapeutic agents. In this review, we evaluate the feasibility
      of both direct and indirect miRNA mimics and inhibitors toward the regulation of
      neurodegenerative-related genes both in vivo and in vitro models, highlight the
      advantages and drawbacks associated with miRNA-based therapy, and summarize the
      relevant techniques and approaches attempted to deliver miRNAs to the central
      nervous system for therapeutic purposes, with particular regard to the exosomes.
      Additionally, we describe a new approach that holds great promise for the
      treatment of a wide range of diseases including neurodegenerative disorders. This
      approach is based on addressing the incorporation of miRNAs into exosomes to
      increase the quantity and quality of miRNA packed and delivered to the central
      nervous system and other sites of action.

PMID- 29357792
TI  - Nonviral Delivery Systems for Cancer Gene Therapy: Strategies and Challenges.
AB  - Gene therapy has been receiving widespread attention due to its unique advantage
      in regulating the expression of specific target genes. In the field of cancer
      gene therapy, modulation of gene expression has been shown to decrease oncogenic
      factors in cancer cells or increase immune responses against cancer. Due to the
      macromolecular size and highly negative physicochemical features of plasmid DNA,
      efficient delivery systems are an essential ingredient for successful gene
      therapy. To date, a variety of nanostructures and materials have been studied as
      nonviral gene delivery systems. In this review, we will cover nonviral delivery
      strategies for cancer gene therapy, with a focus on target cancer genes and
      delivery materials. Moreover, we will address current challenges and perspectives
      for nonviral delivery-based cancer gene therapeutics.

PMID- 29357793
TI  - Vascular Risk Factors and Lesions of Vascular Nature in Magnetic Resonance as
      Predictors of Progression to Dementia in Patients with Mild Cognitive Impairment.
AB  - BACKGROUND: Evidence of the effect of vascular risk factors and white matter
      lesions on the progression of mild cognitive impairment (MCI) to dementia is not
      conclusive. OBJECTIVE: The study aimed to analyze the impact of these factors on
      MCI progression to dementia from a global perspective. METHODS: Our study
      included a population of 105 patients with MCI. RESULTS: After a mean follow-up
      period of 3.09 years (range, 2-3.79), 47 patients (44.76%) progressed to
      dementia: 32 (30.8%) to mixed dementia, 13 (12.5%) to probable AD, and 2 (1.9%)
      to vascular dementia. Total cholesterol levels (OR: 1.015 [1.003-1.028]) and LDL
      cholesterol levels (OR: 1.018 [1.004-1.032]) increased the risk of progression to
      dementia. Cystatin C was a protective factor against progression to dementia (OR:
      0.119 [0.015-0.944], p = 0.044). During the second year of follow-up, the
      presence of subcortical white matter hyperintensities increased the risk of
      progression to dementia (OR: 5.854 [1.008- 33.846]). Subcortical and
      periventricular white matter hyperintensities were also associated with an
      increased risk of progression to dementia during the second year of follow-up
      (OR: 3.130 [1.098-8.922] and OR: 3.561 [1.227-10.334], respectively). The same
      was true for silent infarcts (OR: 4.308 [1.480- 12.500]). CONCLUSION: A high
      percentage of patients progressed to dementia. Total cholesterol, LDL
      cholesterol, and white matter hyperintensities were found to be associated with
      MCI progression to dementia. In contrast, cystatin C was shown to be a protective
      factor against progression to dementia.

PMID- 29357794
TI  - AbetaPP-induced UPR Transcriptomic Signature of Glial Cells to Oxidative Stress
      as an Adaptive Mechanism to Preserve Cell Function and Survival.
AB  - BACKGROUND: Alzheimer's disease (AD) and age-related macular degeneration (AMD)
      present similarities, particularly with respect to oxidative stress, including
      production of 4-Hydroxy-2- nonenal (HNE). AMD has been named the AD in the eye.
      The Muller cells (MC) function as a principal glia of the retina and maintain
      water/potassium, glutamate homeostasis and redox status. Any MC dysfunction
      results in retinal neurodegeneration. OBJECTIVES: We investigated the effects of
      HNE in human MC. RESULTS: HNE induced an increase of the reactive oxygen species
      associated with mitochondrial dysfunction and apoptosis. HNE induced endoplasmic
      reticulum (ER) stress (upregulation of GRP78/Bip, and the proapoptotic factor,
      CHOP). HNE also impaired expression of genes controlling potassium homeostasis
      (KCNJ10), glutamate detoxification (GS), and the visual cycle (RLBP1). MC
      adaptive response to HNE included upregulation of amyloid-beta protein precursor
      (AbetaPP). To determine the role of AbetaPP, we overexpressed AbetaPP in MC.
      Overexpression of AbetaPP induced strong antioxidant and anti-ER stress (PERK
      downregulation and GADD34 upregulation) responses accompanied by activation of
      the prosurvival branch of the unfolded protein response. It was also associated
      with upregulation of major genes involved in MC-controlled retinal homeostasis
      (KCNJ10, GS, and RLBP1) and protection against HNE-induced apoptosis. Therefore,
      AbetaPP is an ER and oxidative stress responsive molecule, and is able to
      stimulate the transcription of major genes involved in MC functions impaired by
      HNE. CONCLUSION: Our study suggests that targeting oxidative and ER stress might
      be a potential therapeutic strategy against glia impairment in AMD and AD, in
      light of the common features between the two pathologies.

PMID- 29357795
TI  - Tolfenamic Acid: A Modifier of the Tau Protein and its Role in Cognition and
      Tauopathy.
AB  - BACKGROUND: Tangles are deposits of hyperphosphorylated tau, which are found in
      multiple neurodegenerative disorders that are referred to as tauopathies, of
      which Alzheimer's disease (AD) is the most common. Tauopathies are clinically
      characterized by dementia and share common cortical lesions composed of
      aggregates of the protein tau. OBJECTIVE: In this study, we explored the
      therapeutic potential of tolfenamic acid (TA), in modifying disease processes in
      a transgenic animal model that carries the human tau gene (hTau). METHODS:
      Behavioral tests, Western blotting and Immunohistochemical analysis were used to
      demonstrate the efficacy of TA. RESULTS: Treatment of TA improved improving
      spatial learning deficits and memory impairments in young and aged hTau mice.
      Western blot analysis of the hTau protein revealed reductions in total tau as
      well as in sitespecific hyperphosphorylation of tau in response to TA
      administration. Immunohistochemical analysis for phosphorylated tau protein
      revealed reduced staining in the frontal cortex, hippocampus, and striatum in
      animals treated with TA. CONCLUSION: TA holds the potential as a disease
      modifying agent for the treatment of tauopathies including AD.

PMID- 29357796
TI  - Autoimmunity and Frontotemporal Dementia.
AB  - BACKGROUND: Frontotemporal Dementia (FTD) is a neurodegenerative disorder which
      asymmetrically affects the frontotemporal lobe, characterized by behavioural
      abnormalities, language impairment, and deficits of executive functions. Genetic
      studies identified mutations causing the disease, namely Microtubule Associated
      Protein Tau (MAPT), Granulin (GRN) and chromosome 9 open reading frame 72
      (C9orf72) mutations, which contributed to elucidate the molecular pathways
      involved in brain depositions of either Tau or TAR DNA-binding protein 43 (TDP43)
      inclusions. However, in the majority of sporadic FTD patients, the mechanisms
      triggering Tau or TDP43 protein deposition are still to be uncovered. OBJECTIVE:
      We aimed to present an extensive evaluation of literature data on immune
      homeostasis in FTD, in order to provide potentially evidence-based approaches for
      a disease still orphan of any treatment. METHODS: A structured search of
      bibliographic databases from peer-reviewed literature was pursued focusing on
      autoimmunity in the brain and FTD. RESULTS: One-hundred-fourteen papers were
      included in this review. The majority of studies (32) were represented by
      extensive literature revision on immunity, central nervous system (CNS) and
      autoimmunity; neuroimaging papers (11) in autoimmune diseases were evaluated, and
      immunomodulatory approaches (25) were revised. Six papers were found specifically
      related to FTD and autoimmune hypothesis, the other papers referring to current
      state of art on FTD. CONCLUSION: Overall this review contribute to expand the
      knowledge of a possible immune hypothesis in FTD, suggesting therapeutic
      perspectives in autoimmune related neurodegeneration, to reduce or revert the
      disease.

PMID- 29357797
TI  - Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta
      Analysis.
AB  - BACKGROUND: beta-amyloid (Abeta) accumulates abnormally to senile plaque which is
      the initiator of Alzheimer's disease (AD). As one of the Abeta-degrading enzymes,
      Insulin-degrading enzyme (IDE) remains controversial for its protein level and
      activity in Alzheimer's brain. METHODS: The electronic databases PubMed, EMBASE,
      The Cochrane Library, OVID and Sinomed were systemically searched up to Sep.
      20th, 2017. And the published case-control or cohort studies were retrieved to
      perform the meta-analysis. RESULTS: Seven studies for IDE protein level (AD cases
      = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and
      three for enzyme activity (AD cases = 123; controls = 75) were pooling together.
      The IDE protein level was significantly lower in AD cases than in controls (SMD =
      - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had
      no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95%
      CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level
      was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [
      0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006
      respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71,
      95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58,
      0.06]). CONCLUSIONS: Our results indicate that AD patients may have lower IDE
      protease level. Further relevant studies are still needed to verify whether IDE
      is one of the factors affecting Abeta abnormal accumulation and throw new
      insights for AD detection or therapy.

PMID- 29357798
TI  - Vascular Risk Factors, Vascular Diseases, and Imaging Findings in a Hospital
      based Cohort of Mild Cognitive Impairment Types.
AB  - BACKGROUND: Mild Cognitive Impairment (MCI) is a transitional state between
      normal cognition and dementia. OBJECTIVE: The aim of this study is to investigate
      the role of vascular risk factors, vascular diseases, cerebrovascular disease and
      brain atrophy in a large hospital-based cohort of MCI types including 471
      amnestic MCI (a-MCI), 693 amnestic MCI multiple domain (a-MCImd), 322 single non
      memory MCI (snm-MCI), and 202 non amnestic MCI multiple domain (na-MCImd). For
      comparison, 1,005 neurologically and cognitively healthy subjects were also
      evaluated. METHOD: Several vascular risk factors and vascular diseases were
      assessed. All participants underwent neurological, neuropsychological and
      behavioural assessments as well as carotid ultrasonography and standard brain
      MRI. Multinomial logistic regression models on the MCI cohort with the NCH group
      and a-MCI type as reference categories were used to assess the effects of the
      variables evaluated on the estimated probability of one of the four MCI types.
      RESULTS: This study demonstrates that cerebrovascular disease contributes
      substantially to the risk of non-memory MCI types and a-MCImd type, and that
      brain atrophy is present in all MCI types and is greater in multiple domain types
      particularly in the na-MCI type. CONCLUSION: Improving detection and control of
      cerebrovascular disease in aging individuals should be mandatory. Since the
      incidence of MCI and dementia will be expected to rise because of the progressive
      life expectancy, a better management of cerebrovascular disease could indeed
      prevent or delay the onset of MCI, or could delay progression of MCI to dementia.

PMID- 29357799
TI  - Estimating Alzheimer's Disease Progression Rates from Normal Cognition Through
      Mild Cognitive Impairment and Stages of Dementia.
AB  - BACKGROUND: Alzheimer's Disease (AD) can be conceptualized as a continuum:
      patients progress from normal cognition to mild cognitive impairment (MCI) due to
      AD, followed by increasing severity of AD dementia. Prior research has measured
      transition probabilities among later stages of AD, but not for the complete
      spectrum. OBJECTIVE: To estimate annual progression rates across the AD continuum
      and evaluate the impact of a delay in MCI due to AD on the trajectory of AD
      dementia and clinical outcomes. METHODS: Patient-level longitudinal data from the
      National Alzheimer's Coordinating Center for n=18,103 patients with multiple
      visits over the age of 65 were used to estimate annual, age-specific transitional
      probabilities between normal cognition, MCI due to AD, and AD severity states
      (defined by Clinical Dementia Rating score). Multivariate models predicted the
      likelihood of death and institutionalization for each health state, conditional
      on age and time from the previous evaluation. These probabilities were used to
      populate a transition matrix describing the likelihood of progressing to a
      particular disease state or death for any given current state and age. Finally, a
      health state model was developed to estimate the expected effect of a reduction
      in the risk of transitioning from normal cognition to MCI due to AD on disease
      progression rates for a cohort of 65-year-old patients over a 35-year time
      horizon. RESULTS: Annual transition probabilities to more severe states were 8%,
      22%, 25%, 36%, and 16% for normal cognition, MCI due to AD, and
      mild/moderate/severe AD, respectively, at age 65, and increased as a function of
      age. Progression rates from normal cognition to MCI due to AD ranged from 4% to
      10% annually. Severity of cognitive impairment and age both increased the
      likelihood of institutionalization and death. For a cohort of 100 patients with
      normal cognition at age 65, a 20% reduction in the annual progression rate to MCI
      due to AD avoided 5.7 and 5.6 cases of MCI due to AD and AD, respectively. This
      reduction led to less time spent in severe AD dementia health states and
      institutionalized, and increased life expectancy. CONCLUSION: Transition
      probabilities from normal cognition through AD severity states are important for
      understanding patient progression across the AD spectrum. These estimates can be
      used to evaluate the clinical benefits of reducing progression from normal
      cognition to MCI due to AD on lifetime health outcomes.

PMID- 29357801
TI  - The Chemical Design and Synthesis of Linkers Used in Antibody Drug Conjugates.
AB  - Antibody Drug Conjugates (ADCs) use targeting ability of monoclonal antibodies to
      deliver potent cytototoxic payloads to their intended target. The linker
      encompasses a conjugating functionality suitable for attachment to the antibody,
      a spacer unit that typically incorporates a hydrophilic element and a trigger
      which releases the potent cytototoxic warhead. Understanding the conflicting
      requirements of ADC design, providing stability in systemic circulation but
      efficient payload release once the ADC reaches its intended target, is crucial to
      effective linker development. ADC linker design has been approached in a variety
      of different ways, with increasingly elegant solutions continuing to be reported
      as understanding of the intricate design complexities increases. This review
      focuses on the synthetic approaches used in ADC linkers, and the impact of linker
      design on antibody conjugation, ADC pharmacokinetics and payload release. Linker
      approaches utilized in commercial ADCs as well as ADCs currently in clinical, pre
      clinical and early stage development are discussed.

PMID- 29357800
TI  - Anti-Inflammatory Activity and Cheminformatics Analysis of New Poten t 2
      Substituted 1-Methyl-5-Nitroindazolinones.
AB  - After the identification of the anti-inflammatory properties of VA5-13l (2-benzyl
      1- methyl-5-nitroindazolinone) in previous investigations, some of its analogous
      compounds were designed, synthesized and evaluated in two anti-inflammatory
      methods: LPS-enhanced leukocyte migration assay in zebrafish; and 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. The products
      evaluated (3, 6, 8, 9 and 10) showed the lower values of relative leukocyte
      migration at 30 &#181;M (0.14, 0.07, 0.10, 0.13 and 0.07, respectively), while in
      ear edema and myeloperoxidase activity methods, all the compounds reduced
      inflammation, only 4 and 16 yielded unsatisfactory results. The relationship
      linking structure and activity (SAR analysis) was determinate by using SARANEA
      software. The importance of the 5-Nitro group of the indazole ring for the
      activity was evident, and showed modest reduction when benzyl (Bn) is changed by
      alkyl group. A substituted Bn moiety at N2 (R) is the best substituent (5-10);
      nevertheless, if methylene group of Bn is deleted, the activity is affected.
      Also, introduction of halogen atoms mainly at positions 3 or 4 of the benzyl
      moiety (6 and 10) leads in general to strong activities. In fact, compounds 7 and
      8 (R = 4-FBn or 4-ClBn, respectively) exhibit satisfactory results in in vivo
      tests and appear promising. The production of IL-6 at all doses assayed was
      significantly reduced, except with 16. Nonetheless, the production of TNF-alpha
      was significantly inhibited only by this chemical (16) at concentration of 50
      MUM. On the other hand, compound 2 was the one that mostly inhibited the
      expression of COX-2 and iNOS. From these results, it can be concluded that the
      inhibition in the release of cytokines can be one of the mechanisms of action
      responsible for the anti-inflammatory effect for 2-benzyl derivates while other 2
      alkyl derivatives can inhibit production of NO. Therefore, nitroindazolinone
      chemical prototype could be an interesting structural group with anti
      inflammatory purposes in the therapeutic.

PMID- 29357803
TI  - ADME Considerations for the Development of Biopharmaceutical Conjugates Using
      Cleavable Linkers.
AB  - The recent approval of trastuzumab emtansine (Kadcyla(r)) and brentuximab vedotin
      (Adcetris (r)) has spurred tremendous investment in new approaches for the
      targeted delivery of pharmaceutical agents. Targeted delivery approaches, such as
      Antibody Drug Conjugates (ADCs), typically rely on an endogenous or exogenous
      "trigger" that results in the release of the pharmacologically active agent at
      the intended site of action. Lysosomal and intracellular triggers include
      proteolytic cleavage, glycolytic cleavage, phosphatase cleavage, hydrolytic
      cleavage, and reductive cleavage. Recent work has also illustrated that exogenous
      triggers and extracellular enzymes can be harnessed to result in linker cleavage
      at the site of action. As these linker technologies have grown, so also has our
      understanding of the biophysical parameters that drive exposure and stability.
      The growth in targeted delivery approaches has also driven advancement in
      bioanalytical strategies for assessing the distribution, processing, and
      metabolism of these agents. This review provides a systematic overview of each of
      these areas, particularly focusing on recent advancements in the field that has
      the potential to expand the scope of therapeutic areas that ADCs and other
      targeted delivery approaches can be designed to address.

PMID- 29357804
TI  - ADME and Safety Aspects of Non-cleavable Linkers in Drug Discovery and
      Development.
AB  - Non-cleavable linkers are used in a number of different modalities for various
      reasons, such as linking an active drug moiety to half-life extending molecules,
      to groups that enable a specific tissue or cell targeting or to facilitate active
      uptake into target cells. Non-cleavable linkers do not have a designated weak
      point in their structure that can lead to cleavage by proteases, hydrolases or
      chemically by pH changes. Consequently, when designing a conjugate, the choice of
      a non-cleavable over a cleavable linker is usually a consequence of pursuing a
      certain mode of action where the stability of the complex is more important than
      a fast liberation of the active moiety. Linkers of various length, polarity,
      stability and flexibility are used for different types of conjugates and the
      linker design is mostly driven by the particular purpose and desired mode of
      action. This article reviews non-cleavable linkers applied predominantly in
      Antibody Drug Conjugates (ADCs), and how they influence these conjugates in terms
      of ADME properties (absorption, distribution, metabolism and elimination) and
      safety.

PMID- 29357802
TI  - Conjugates of Cell Adhesion Peptides for Therapeutics and Diagnostics Against
      Cancer and Autoimmune Diseases.
AB  - Overexpressed cell-surface receptors are hallmarks of many disease states and are
      often used as markers for targeting diseased cells over healthy counterparts.
      Cell adhesion peptides, which are often derived from interacting regions of these
      receptor-ligand proteins, mimic surfaces of intact proteins and, thus, have been
      studied as targeting agents for various payloads to certain cell targets for
      cancers and autoimmune diseases. Because many cytotoxic agents in the free form
      are often harmful to healthy cells, the use of cell adhesion peptides in
      targeting their delivery to diseased cells has been studied to potentially reduce
      required effective doses and associated harmful side-effects. In this review,
      multiple cell adhesion peptides from extracellular matrix and ICAM proteins were
      used to selectively direct drug payloads, signal-inhibitor peptides, and
      diagnostic molecules, to diseased cells over normal counterparts. RGD constructs
      have been used to improve the selectivity and efficacy of diagnostic and drug
      peptide conjugates against cancer cells. From this precedent, novel conjugates of
      antigenic and cell adhesion peptides, called Bifunctional Peptide Inhibitors
      (BPIs), have been designed to selectively regulate immune cells and suppress
      harmful inflammatory responses in autoimmune diseases. Similar peptide
      conjugations with imaging agents have delivered promising diagnostic methods in
      animal models of rheumatoid arthritis. BPIs have also been shown to generate
      immune tolerance and suppress autoimmune diseases in animal models of type-1
      diabetes, rheumatoid arthritis, and multiple sclerosis. Collectively, these
      studies show the potential of cell adhesion peptides in improving the delivery of
      drugs and diagnostic agents to diseased cells in clinical settings.

PMID- 29357806
TI  - Correlation between White Blood Cell Count and insulin resistance in type 2
      Diabetes
AB  - BACKGROUND: The role of chronic inflammation in insulin resistance states and the
      pathogenesis of metabolic syndrome, cardiovascular disease and diabetes have been
      reported earlier. White blood cell (WBC) count is an easy marker for estimation
      of systemic inflammation. OBJECTIVE: This study is to clarify whether WBC count
      associate with insulin resistance in type 2 diabetic patients. METHOD: This cross
      sectional study was conducted in 283 patients with type 2 diabetes and in 283
      healthy non diabetic subjects as control group. Data including: age, gender,
      blood pressure, height and weight, history of smoking were collected for each
      patient. Fasting blood sugar, HbA1C, insulin, lipid profiles, creatinine, Urine
      albumin to creatinine ratio, high sensitive C- reactive protein (HCRP) and WBC
      was measured for all patients. WBC count was measured in control group. Two
      groups were compared in WBC count. Insulin resistance was calculated with HOMA-IR
      formula. Association of WBC count with insulin resistance and metabolic
      parameters was assessed in diabetic patients. RESULTS: WBC count was
      significantly associated with body mass index, hypertension, and triglyceride
      level. There was not significant association between WBC count and glycemic index
      and insulin resistance. CONCLUSION: An elevated WBC count (even in the normal
      range) is closely related to various components of metabolic syndrome but not
      related to insulin resistance in type 2 diabetes.

PMID- 29357807
TI  - Hyperglycemia in hospitalized diabetic non-critically ill patients: Prevalence,
      correlates, management and nurses' attitudes.
AB  - BACKGROUND: Diabetes Mellitus is a chronic metabolic disease that affects 387
      million people around the world. Episodes of hyperglycemia in hospitalized
      diabetic patients are associated with poor clinical outcomes and increased
      morbidity and mortality. Therefore, prevention of hyperglycemia is critical to,
      decrease length of hospital stay and to reduce complications and readmissions.
      OBJECTIVE: The study aims to examine the prevalence of hyperglycemia and assess
      the correlates and management of hyperglycemia in diabetic non-critically ill
      patients. METHOD: The study was conducted on the medical wards of a tertiary care
      teaching hospital in Lebanon. A retrospective chart review was conducted from
      January 2014 until September 2015. Diabetic patients admitted to Internal
      Medicine floors were identified. Descriptive analysis was first carried out,
      followed by a multivariable analysis to study the correlates of hyperglycemia
      occurrence. RESULTS: A total of 235 medical charts were reviewed. Seventy percent
      of participants suffered from hyperglycemia during their hospital stay. The
      identified significant positive correlates for hyperglycemia, were the inpatient
      use of insulin sliding scale alone (OR=16.438 +/- 6.765-39.941, p=0.001) and the
      low frequency of glucose monitoring. Measuring glucose every 8 hours (OR= 3.583
      +/- 1.506-8.524, p=0.004) and/or every 12 hours (OR=7.647 +/- 0.704-79.231,
      p=0.0095) was associated with hyperglycemia. The major factor perceived by nurses
      as a barrier to successful hyperglycemia management was the lack of knowledge
      about appropriate insulin use (87.5%) Conclusion: Considerable mismanagement of
      hyperglycemia in diabetic non-critically ill patients exists; indicating a
      compelling need for the development and implementation of protocol-driven insulin
      order forms.

PMID- 29357808
TI  - The role of oestrogen receptor beta (ERbeta) in the aetiology and treatment of
      type 2 diabetes mellitus.
AB  - INTRODUCTION: Challenges facing the treatment of type 2 diabetes necessitate the
      search for agents which act via alternative pathways to provide better
      therapeutic outcomes. Recently, an increasing body of evidence implicates the
      activation of oestrogen receptors (ERalpha and ERbeta) in the development and
      treatment of underlying conditions in type 2 diabetes. This article summarizes
      available evidence for the involvement of oestrogen receptors in insulin
      secretion, insulin resistance as well as glucose uptake and highlights the
      potential of ERbeta as a therapeutic target. BACKGROUND: Recent studies indicate
      an association between the activation of each of the isoforms of ER and recent
      findings indicate that ERbeta show promise as a potential target for antidiabetic
      drugs. In vitro and in vivo studies in receptor knock out mice indicate
      beneficial actions of selective agonists of ERbeta receptor and underscore its
      therapeutic potential. CONCLUSION: Studies are needed to further elucidate the
      exact mechanism underlying the role of ERbeta activation as a therapeutic
      approach in the management of type 2 diabetes.

PMID- 29357805
TI  - Protein-C Reactive as Biomarker Predictor of Schizophrenia Phases of Illness? A
      Systematic Review.
AB  - BACKGROUND: Schizophrenia is a complex illness in which genetic, environmental,
      and epigenetic components have been implicated. However, recently, psychiatric
      disorders appear to be related to a chronic inflammatory state, at the level of
      specific cerebral areas which have been found as well impaired and responsible
      for schizophrenia symptomatology. Hence, a role of inflammatory mediators and
      cytokines has been as well defined. Accordingly, the role of an acute
      inflammatory phase protein, the C-reactive protein (CRP) has been recently
      investigated. OBJECTIVE: The objective of the present study is to evaluate how
      PCR may represent a biomarker in schizophrenia, i.e. correlated with illness
      phases and/or clinical manifestation and/or psychopathological severity. METHODS:
      A systematic review was here carried out by searching the following keywords ((C
      reactive protein AND ((schizophrenia) OR (psychotic disorder))) for the topics
      'PCR' and 'Schizophrenia', by using MESH terms. RESULTS: An immune dysfunction
      and inflammation have been described amongst schizophrenic patients. Findings
      reported elevated CRP levels in schizophrenia, mainly correlated with the
      severity of illness and during the recrudescent phase. CRP levels are higher when
      catatonic features, negative symptomatology and aggressiveness are associated.
      CRP levels appeared not to be related to suicidal behaviour and ideation.
      CONCLUSION: CRP and its blood levels have been reported higher amongst
      schizophrenic patients, by suggesting a role of inflammation in the pathogenesis
      of schizophrenia. Further studies are needed to better understand if CRP may be
      considered a biomarker in schizophrenia.

PMID- 29357809
TI  - Coagonist of GLP-1 and Glucagon Receptor Ameliorates Development of Non-Alcoholic
      Fatty Liver Disease.
AB  - BACKGROUND: Obesity, diabetes and dyslipidemica are the key pathogenic stimulus
      that enhances progression of Non-Alcoholic Fatty Liver Disease (NAFLD). Coagonist
      of Glucagon Like- Peptide-1 (GLP-1) Receptor (GLP-1R) and Glucagon Receptor
      (GCGR) are being evaluated for obesity and diabetes. GLP-1 analogs have shown to
      reverse diabetes and obesity. Glucagon treatment reduces lipids after acute and
      chronic treatment. OBJECTIVE: In this study, we have investigated the effect of
      co-agonist on the prevention of NAFLD induced by long-term feeding of High Fat
      Diet (HFD). METHOD: We have used HFD to induce NAFLD after chronic feeding in
      mice. Co-agonist treatment (150 ug.kg-1, s.c.) was initiated with induction of
      HFD, which was continued for 40 weeks. Body weight, food intake, glucose
      homeostasis, lipid profile, inflammatory and fibrotic markers were assessed at
      the end of treatment. RESULTS: Co-agonist treatment prevented body weight gain,
      glucose intolerance and insulin resistance. Treatment with co-agonist reduced
      NEFA, increased FGF21 and adiponectin levels. Co-agonist increased glycerol
      release and energy expenditure, while decreased respiratory quotient. Co-agonist
      reduced lipids in circulation and liver. Expression of SREBP-1C, SCD-1, ACC and
      FAS were decreased, while ACOX1 and CPT1 were increased after co-agonist
      treatment. Inflammatory cytokine TNF-alpha and IL-6 in plasma and expression of
      MCP-1, TGF-beta, MMP-9, TNF-alpha, TIMP-1, alpha-SMA, and COL1A1 were decreased
      after co-agonist treatment. Plasma transaminases, hepatic TBARS, hepatic
      hydroxyproline and relative liver weight were suppressed after co-agonist
      treatment. Fat accumulation, inflammation and fibrosis were reduced in
      histological assessment of liver in co-agonist treated animals. CONCLUSION: Co
      agonist prevented development of HFD-induced NAFLD by ameliorating obesity,
      diabetes, inflammation and fibrosis.

PMID- 29357810
TI  - Cytochrome P450 1A2 Messenger RNA is a More Reliable Marker than Cytochrome P450
      1A2 Activity, Phenacetin O-Deethylation, for Assessment of Induction Potential of
      Drug-Metabolizing Enzymes Using HepaRG Cells.
AB  - BACKGROUND: The HepaRG cells have key drug metabolism functionalities comparable
      to those of primary human hepatocytes. Many studies have reported that this cell
      line can be used as a reliable in vitro model for human drug metabolism studies,
      including the assessment of cytochrome P450 (CYP) induction. OBJECTIVES: The
      objective of this study is to determine whether CYP mRNA level measurement is
      superior to the CYP enzyme activity measurement as a convenient high-throughput
      method for evaluating CYP induction potential using HepaRG cells. METHODS:
      QuantiGene Plex 2.0 Assay and LC/MS/MS. mRNA expression levels and enzyme
      activities of CYP1A2, CYP2B6, and CYP3A in HepaRG cells treated with prototypical
      inducers of each CYP isoform [omeprazole (OME) for CYP1A2, phenobarbital (PB) for
      CYP2B6, and rifampicin (RIF) for CYP3A] were evaluated. RESULTS: Although the
      activities of CYP2B6 and CYP3A were induced by treatment with PB and RIF, we
      found that the activity of phenacetin O-deethylase (PHOD), which is known as a
      marker of the activity of CYP1A2, was also enhanced by treatment with these non
      CYP1A2 inducers in HepaRG cells. Based on previously published reports, we
      hypothesized that the expression ratio of CYP3A to CYP1A2 is much higher in
      HepaRG cells than in human hepatocytes; this may result in a nonnegligible
      contribution of CYP3A to the PHOD reaction in HepaRG cells. Studies using CYP3A
      inhibitor and pregnane X receptor-knockout HepaRG cells supported this
      hypothesis. CONCLUSION: The measurement of mRNA serves as a higher reliable
      indicator for the evaluation of CYP induction potential when using HepaRG cells.

PMID- 29357811
TI  - Targeting M3 Muscarinic Receptors for Colon Cancer Therapy.
AB  - BACKGROUND: Expression and activation of subtype-3 muscarinic receptors (M3R)
      plays an important role in the progression of colorectal neoplasia. METHOD:
      Herein, we describe the role of muscarinic receptors in colon cancer, focusing
      specifically on M3R, illustrate how M3R over-expression and activation of post
      receptor signaling pathways potentiates tumor progression, and explore the
      efficacy and safety of a variety of therapeutic approaches that can target the
      molecules involved. RESULTS: Colon cancers overexpress M3R mRNA (CHRM3) and
      protein, and post-M3R signaling stimulates cell proliferation. Post-M3R signal
      transduction is complex, involving interplay between epidermal growth factor
      receptors (EGFR)/ERK and protein kinase C (PKC)/p38 mitogen-activated protein
      (MAP) kinase signaling pathways. In particular, the development of an invasive
      and metastatic phenotype requires that these signaling interactions augment
      cellular release of a key collagenase, matrix metalloproteinase-1 (MMP1).
      Blocking either M3R activation or post-M3R signaling attenuates MMP1 release and
      colon cancer invasiveness. CONCLUSION: Parsing the complexities of these
      signaling interactions is important, not only to understand these mechanisms of
      cancer initiation and progression, but also to develop novel treatment
      modalities. Since the vast majority of persons with colon cancer die from
      disseminated disease, preventing or reversing metastatic spread of cancer cells
      by targeting M3R, post-M3R signaling, or MMP1 has therapeutic potential.

PMID- 29357812
TI  - The invasive MED/Q Bemisia tabaci genome: a tale of gene loss and gene gain.
AB  - BACKGROUND: Sweetpotato whitefly, Bemisia tabaci MED/Q and MEAM1/B, are two
      economically important invasive species that cause considerable damages to
      agriculture crops through direct feeding and indirect vectoring of plant
      pathogens. Recently, a draft genome of B. tabaci MED/Q has been assembled. In
      this study, we focus on the genomic comparison between MED/Q and MEAM1/B, with a
      special interest in MED/Q's genomic signatures that may contribute to the highly
      invasive nature of this emerging insect pest. RESULTS: The genomes of both
      species share similarity in syntenic blocks, but have significant divergence in
      the gene coding sequence. Expansion of cytochrome P450 monooxygenases and UDP
      glycosyltransferases in MED/Q and MEAM1/B genome is functionally validated for
      mediating insecticide resistance in MED/Q using in vivo RNAi. The amino acid
      biosynthesis pathways in MED/Q genome are partitioned among the host and
      endosymbiont genomes in a manner distinct from other hemipterans. Evidence of
      horizontal gene transfer to the host genome may explain their obligate
      relationship. Putative loss-of-function in the immune deficiency-signaling
      pathway due to the gene loss is a shared ancestral trait among hemipteran
      insects. CONCLUSIONS: The expansion of detoxification genes families, such as
      P450s, may contribute to the development of insecticide resistance traits and a
      broad host range in MED/Q and MEAM1/B, and facilitate species' invasions into
      intensively managed cropping systems. Numerical and compositional changes in
      multiple gene families (gene loss and gene gain) in the MED/Q genome sets a
      foundation for future hypothesis testing that will advance our understanding of
      adaptation, viral transmission, symbiosis, and plant-insect-pathogen tritrophic
      interactions.

PMID- 29357814
TI  - "You just need to leave the room when you breastfeed" Breastfeeding experiences
      among obese women in Sweden - A qualitative study.
AB  - BACKGROUND: The benefits of breastfeeding for the infant as well for the mother
      are well-known. It is recognized that obese (Body Mass Index >=30 kg/m2) women
      may have less antenatal intention to breastfeed, and shortened duration of
      breastfeeding compared with normal-weight women. This may result in adverse short
      and long-term health for both mother and child, such as a shortened lactational
      amenorrhoea and decreased protection against breast cancer for the women, and an
      increased risk for infectious diseases and overweight/obesity among the children.
      Therefore, it is important to gain more knowledge and understanding of obese
      women's experiences of breastfeeding in order to attain good health care. Hence,
      the aim of this study was to identify and describe obese women's experiences of
      breastfeeding. METHODS: This is an explorative study. Data was collected 2 - 18
      months after childbirth through semi-structured face-to-face interviews with 11
      obese women with breastfeeding experience. The interviews were recorded and
      transcribed verbatim. Thematic analysis was used. RESULTS: Three themes emerged
      from the data analysis: Breastfeeding - a part of motherhood, the challenges of
      breastfeeding, and support for breastfeeding. The women described an antenatal
      hope for breastfeeding, the body's ability to produce milk fascinated them, and
      the breast milk was seen as the best way to feed the child and also as promoting
      the attachment between mother and child. Breastfeeding was described as a
      challenge even though it is natural. The challenges concerned technical
      difficulties such as the woman finding a good body position and helping the child
      to achieve an optimum grip of the nipple. Another challenge was the exposure of
      the body connected to public breastfeeding. Support of breastfeeding was
      described as the importance of being confirmed as an individual behind the
      obesity, rather than an individual with obesity, and to obtain enough
      professional breastfeeding support. CONCLUSIONS: Breastfeeding was experienced as
      a natural part of being a mother. There were practical challenges for obese women
      concerning how to manage breastfeeding and how to handle the public exposure of
      the body. There was a need for realistic information about breastfeeding
      concerning both the child and the woman.

PMID- 29357813
TI  - Dissection of the multigenic wheat stem rust resistance present in the
      Montenegrin spring wheat accession PI 362698.
AB  - BACKGROUND: Research to identify and characterize stem rust resistance genes in
      common wheat, Triticum aestivum, has been stimulated by the emergence of Ug99
      lineage races of the wheat stem rust pathogen, Puccinia graminis f. sp. tritici
      (Pgt), in Eastern Africa. The Montenegrin spring wheat landrace PI 362698 was
      identified as a source of Pgt resistance. This accession exhibits resistance to
      multiple Ug99-lineage and North American Pgt races at seedling and adult-plant
      stages. A recombinant inbred population was developed by crossing the susceptible
      line LMPG-6 with a single plant selection of PI 362698. A genetic map was
      constructed using the Illumina iSelect 90 K wheat assay and the markers csLv34,
      NB-LRR3, and wMAS000003 and quantitative trait locus (QTL) analysis was
      performed. RESULTS: QTL analysis identified five significant QTLs (alpha = 0.05)
      on chromosomes 2B, 3B, 6A, 6D, and 7A associated with wheat stem rust resistance.
      The QTL on chromosome 3B was identified using both field data from Kenya (Pgt
      Ug99-lineage races) and seedling data from Pgt race MCCF. This QTL potentially
      corresponds to Sr12 or a new allele of Sr12. The multi-pathogen resistance gene
      Sr57 located on chromosome 7D is present in PI 362698 according to the diagnostic
      markers csLv34 and wMAS000003, however a significant QTL was not detected at this
      locus. The QTLs on chromosomes 2B, 6A, and 6D were identified during seedling
      trials and are thought to correspond to Sr16, Sr8a, and Sr5, respectively. The
      QTL identified on chromosome 7A was detected using MCCF seedling data and may be
      Sr15 or a potentially novel allele of recently detected Ug99 resistance QTLs.
      CONCLUSIONS: The combination of resistance QTLs found in PI 362698 is like the
      resistance gene combination present in the broadly resistant cultivar Thatcher.
      As such, PI 362698 may not be a landrace as previously thought. PI 362698 has
      been crossed with North Dakota wheat germplasm for future breeding efforts.
      Additional work is needed to fully understand why the combination of genes
      present in PI 362698 and 'Thatcher' provide such durable resistance.

PMID- 29357815
TI  - The effect of a gerontology nurse specialist for high needs older people in the
      community on healthcare utilisation: a controlled before-after study.
AB  - BACKGROUND: Nurse-led models of comprehensive geriatric assessment and care
      coordination can improve health management as well as reduce hospitalisations for
      high risk community dwelling older people. This study investigated the effect on
      healthcare utilisation of systematic case finding to identify high risk older
      people in the community with a subsequent comprehensive assessment and care
      coordination intervention by a Gerontology Nurse Specialist based in primary
      care. METHODS: This was a controlled before-after study design located within
      primary healthcare practices in Auckland, New Zealand. An intervention model was
      initiated within two primary healthcare practices and involved a screening tool
      to identify high risk older people with succeeding gerontology nurse specialist
      assessment and care coordination. The comparison group included older people who
      received usual care at three comparable primary healthcare practices. The primary
      outcome measure was acute hospital admissions. Secondary outcomes included
      hospital re-admissions, length of stay, emergency department presentations,
      residential care admissions, and community contacts. RESULTS: A total of 579
      older people were posted the screening tool in the intervention group, with 517
      completed screens (89% response rate) formulating the intervention group. A total
      of 101 older people were identified as high risk from these screens (20%). The
      comparison group comprised 883 older people. Comparing the intervention and
      comparison group, no statistical differences were found for hospital admissions,
      emergency department presentations, hospital re-admissions, length of stay, or
      residential care admission. Community physiotherapy showed a statistically
      significant increase for the intervention compared to the comparison group (p =
      0.03). Non-significant findings revealed decreased risk of entering residential
      care and fewer frequent hospital re-admissions for the intervention group when
      compared with the comparison group. CONCLUSIONS: This specialist nurse-led
      intervention involving comprehensive assessment and care coordination care did
      not appear superior to usual care, however, there is benefit to exploring a more
      robust randomised controlled trial design. TRIAL REGISTRATION: Retrospectively
      registered on 18/09/2017 with the Australian New Zealand Clinical Trials Registry
      (ANZCTR). Registration number ACTRN12617001332314.

PMID- 29357816
TI  - Guillain-Barre syndrome caused by hepatitis E infection: case report and
      literature review.
AB  - BACKGROUND: Hepatitis E infection is a global disorder that causes substantial
      morbidity. Numerous neurologic illnesses, including Guillain-Barre syndrome
      (GBS), have occurred in patients with hepatitis E virus (HEV) infection. CASE
      PRESENTATION: We report a 58 year-old non-immunocompromised man who presented
      with progressive muscle weakness in all extremities during an episode of acute
      HEV infection, which was confirmed by measuring the anti-HEV IgM antibodies in
      the serum. Both cerebrospinal fluid examination and electrophysiological study
      were in agreement with the diagnosis of HEV-associated GBS. Following the
      treatment with intravenous immunoglobulin, the patient's neurological condition
      improved rapidly. CONCLUSIONS: HEV infection should be strongly considered in
      patients with neurological symptoms, especially those with elevated levels of
      liver enzymes.

PMID- 29357817
TI  - Feature selection for high-dimensional temporal data.
AB  - BACKGROUND: Feature selection is commonly employed for identifying collectively
      predictive biomarkers and biosignatures; it facilitates the construction of small
      statistical models that are easier to verify, visualize, and comprehend while
      providing insight to the human expert. In this work we extend established
      constrained-based, feature-selection methods to high-dimensional "omics" temporal
      data, where the number of measurements is orders of magnitude larger than the
      sample size. The extension required the development of conditional independence
      tests for temporal and/or static variables conditioned on a set of temporal
      variables. RESULTS: The algorithm is able to return multiple, equivalent solution
      subsets of variables, scale to tens of thousands of features, and outperform or
      be on par with existing methods depending on the analysis task specifics.
      CONCLUSIONS: The use of this algorithm is suggested for variable selection with
      high-dimensional temporal data.

PMID- 29357819
TI  - Spontaneous reattachment of dislocated endothelial graft after non-Descemet
      stripping automated endothelial keratoplasty: a case report.
AB  - BACKGROUND: Graft detachment is a complication of non-Descemet stripping
      automated endothelial keratoplasty (nDSAEK). We report a case of spontaneous
      reattachment of an extensively dislocated graft after nDSAEK. CASE PRESENTATION:
      A 54-year-old male underwent penetrating keratoplasty (PKP) for keratoconus in
      his left eye in 2001. Following graft opacity due to rejection, a second PKP was
      implemented in May 2014. The graft was kept in good condition after the
      reoperation and yet, visual acuity (VA) declined due to cataract. PEA+IOL was
      then performed in May 2015. Because edema appeared in the graft 6 months after
      the PEA+IOL, nDSAEK was carried out in May 2016. Although the donor graft well
      attached immediately after the nDSAEK, the graft was almost completely dislocated
      3 h later except a temporal part. Air was reinjected into the anterior chamber on
      the following day and the detachment was resolved. Despite of the treatment,
      about 1/5 of the graft remained detached and the detachment deteriorated to 3/4
      of the graft 9 days later. Because the patient could not decide whether to
      undergo another operation immediately, we decided to follow him up first and
      found that the partially detached graft reattached spontaneously 1 month later
      during the follow-up. Although the cornea had a mild edema remaining in the
      superior temporal area, his BCVA improved to 1.0. Three months later, the graft
      remained in position and the cornea kept its transparency. CONCLUSIONS:
      Spontaneous reattachment was observed during the follow-up in a case that had
      shown a comparatively extensive graft dislocation after nDSAEK.

PMID- 29357818
TI  - The association between BDNF Val66Met polymorphism and emotional symptoms after
      mild traumatic brain injury.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is one of the most abundant
      neurotrophins in the adult brain, and it plays important roles in modulating
      synaptic plasticity and synaptogenesis. This study attempted to elucidate the
      role of the BDNF variant rs6265 in emotional symptoms following mild traumatic
      brain injury (mTBI). METHODS: To investigate the association between BDNF
      Val66Met polymorphism (rs6265) and emotional symptoms in mTBI patients, we
      recruited 192 mTBI patients and evaluated their Beck Anxiety Inventory (BAI) and
      Beck Depression Inventory (BDI) scores in the first and sixth week after mTBI.
      RESULTS: The patients carrying the T allele of rs6265 had significantly higher
      BAI scores in the first week following mTBI. In addition, the patients carrying
      the T allele also showed higher scores of BDI in the first week. In the gender
      specific subgroup analysis, the male patients carrying the T allele of rs6265 had
      higher scores of both BAI and BDI in the first and sixth week. Meanwhile, female
      patients carrying the T allele also had significantly higher scores of BDI in the
      first week following mTBI. CONCLUSIONS: This study provides evidence for the
      association between the BDNF variant rs6265 and emotional symptoms following
      mTBI.

PMID- 29357820
TI  - No effect of adding dairy lipids or long chain polyunsaturated fatty acids on
      formula tolerance and growth in full term infants: a randomized controlled trial.
AB  - BACKGROUND: When breastfeeding is not possible, infants are fed formulas in which
      lipids are usually of plant origin. However, the use of dairy fat in combination
      with plant oils enables a lipid profile in formula closer to breast milk in terms
      of fatty acid composition, triglyceride structure and cholesterol content. The
      objectives of this study were to investigate the impact on growth and
      gastrointestinal tolerance of a formula containing a mix of dairy lipids and
      plant oils in healthy infants. METHODS: This study was a monocentric, double
      blind, controlled, randomized trial. Healthy term infants aged less than 3 weeks
      whose mothers did not breastfeed were randomly allocated to formula containing
      either: a mix of plant oils and dairy fat (D), only plant oils (P) or plant oils
      supplemented with long-chain polyunsaturated fatty acids (PDHA). Breastfed
      infants were included in a reference group (BF). Anthropometric parameters and
      body composition were measured after 2 and 4 months. Gastrointestinal tolerance
      was evaluated during 2 day-periods after 1 and 3 months thanks to descriptive
      parameters reported by parents. Nonrandomized BF infants were not included in the
      statistical analysis. RESULTS: Eighty eight formula-fed and 29 BF infants were
      enrolled. Gains of weight, recumbent length, cranial circumference and fat mass
      were similar between the 3 formula-fed groups at 2 and 4 months and close to
      those of BF. Z-scores for weight, recumbent length and cranial circumference in
      all groups were within normal ranges for growth standards. No significant
      differences were noted among the 3 formula groups in gastrointestinal parameters
      (stool frequency/consistency/color), occurrence of gastrointestinal symptoms
      (abdominal pain, flatulence, regurgitation) or infant's behavior. CONCLUSIONS: A
      formula containing a mix of dairy lipids and plant oils enables a normal growth
      in healthy newborns. This formula is well tolerated and does not lead to abnormal
      gastrointestinal symptoms. Consequently, reintroduction of dairy lipids could
      represent an interesting strategy to improve lipid quality in infant formulas.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01611649 , retrospectively
      registered on May 25, 2012.

PMID- 29357821
TI  - Construct validity of the Dining Environment Audit Protocol: a secondary data
      analysis of the Making Most of Mealtimes (M3) study.
AB  - BACKGROUND: Research has demonstrated the importance of physical environments at
      mealtimes for residents in long term care (LTC). However, a lack of a
      standardized measurement to assess physical dining environments has resulted in
      inconsistent research with potentially invalid and unreliable conclusions. The
      development of a standardized, construct valid instrument that assesses dining
      rooms is imperative to systematically examine physical environments in LTC. The
      purpose of this study was to determine the construct validity of the new Dining
      Environment Audit Protocol (DEAP) tool. METHODS: Secondary data collected from
      the Making Most of Mealtimes (M3) study was used for this analysis. Data were
      collected in 32 long term care homes, which included 82 dining rooms and 639
      residents. A variety of resident and dining room level constructs were compared
      to the summative scales found on the DEAP using Spearman correlations and Student
      t-tests. A regression analysis identified individual characteristics assessed
      with DEAP that were associated with the summative scales of homelikeness and
      functionality. RESULTS: Regression analysis (p < 0.05) identified that the DEAP
      homelikeness scale was positively associated with a view of the garden/green
      space, presence of a clock and a posted menu. The functionality scale was
      positively associated with number of chairs and lighting, while negatively
      associated with furniture with rounded edges and clutter. Additionally, the
      functionality scale was positively associated (p < 0.05) with the Mealtime Scan
      physical scale (rho = 0.52), the dining room Mealtime-Relational Care Checklist
      (M-RCC) (rho = 0.25), the DEAP total score (rho = 0.56), and the Mini Nutritional
      Assessment- Short Form (rho = 0.26). Homelikeness was positively associated (p <
      0.05) with the DEAP total score (rho = 0.53), staff Person Directed Care score
      (rho = 0.49) and the resident Cognitive Performance Scale (t = 2.56), while
      negatively associated with energy (rho = -0.26) and protein intake (rho = -0.24).
      The homelikeness and functionality scales were also associated with one another
      (rho = 0.26). CONCLUSION: The construct validity of the DEAP was supported
      through significant correlations with a variety of measures that are
      theoretically related to the homelikeness and functionality of LTC dining rooms.
      This secondary analysis supports the use of the DEAP in future research to
      quantify the physical environment of LTC dining rooms. Protocol registered with
      ClinicalTrials.gov ID: NCT02800291; Registered retrospectively June 7, 2016.

PMID- 29357822
TI  - MutScan: fast detection and visualization of target mutations by scanning FASTQ
      data.
AB  - BACKGROUND: Some types of clinical genetic tests, such as cancer testing using
      circulating tumor DNA (ctDNA), require sensitive detection of known target
      mutations. However, conventional next-generation sequencing (NGS) data analysis
      pipelines typically involve different steps of filtering, which may cause miss
      detection of key mutations with low frequencies. Variant validation is also
      indicated for key mutations detected by bioinformatics pipelines. Typically, this
      process can be executed using alignment visualization tools such as IGV or
      GenomeBrowse. However, these tools are too heavy and therefore unsuitable for
      validating mutations in ultra-deep sequencing data. RESULT: We developed MutScan
      to address problems of sensitive detection and efficient validation for target
      mutations. MutScan involves highly optimized string-searching algorithms, which
      can scan input FASTQ files to grab all reads that support target mutations. The
      collected supporting reads for each target mutation will be piled up and
      visualized using web technologies such as HTML and JavaScript. Algorithms such as
      rolling hash and bloom filter are applied to accelerate scanning and make MutScan
      applicable to detect or visualize target mutations in a very fast way.
      CONCLUSION: MutScan is a tool for the detection and visualization of target
      mutations by only scanning FASTQ raw data directly. Compared to conventional
      pipelines, this offers a very high performance, executing about 20 times faster,
      and offering maximal sensitivity since it can grab mutations with even one single
      supporting read. MutScan visualizes detected mutations by generating interactive
      pile-ups using web technologies. These can serve to validate target mutations,
      thus avoiding false positives. Furthermore, MutScan can visualize all mutation
      records in a VCF file to HTML pages for cloud-friendly VCF validation. MutScan is
      an open source tool available at GitHub: https://github.com/OpenGene/MutScan.

PMID- 29357823
TI  - Chemotherapy weakly contributes to predicted neoantigen expression in ovarian
      cancer.
AB  - BACKGROUND: Patients with highly mutated tumors, such as melanoma or smoking
      related lung cancer, have higher rates of response to immune checkpoint blockade
      therapy, perhaps due to increased neoantigen expression. Many chemotherapies
      including platinum compounds are known to be mutagenic, but the impact of
      standard treatment protocols on mutational burden and resulting neoantigen
      expression in most human cancers is unknown. METHODS: We sought to quantify the
      effect of chemotherapy treatment on computationally predicted neoantigen
      expression for high grade serous ovarian carcinoma patients enrolled in the
      Australian Ovarian Cancer Study. In this series, 35 of 114 samples were collected
      after exposure to chemotherapy; 14 are matched with an untreated sample from the
      same patient. Our approach integrates whole genome and RNA sequencing of bulk
      tumor samples with class I MHC binding prediction and mutational signatures
      extracted from studies of chemotherapy-exposed Caenorhabditis elegans and Gallus
      gallus cells. We additionally investigated the relationship between neoantigens,
      tumor infiltrating immune cells estimated from RNA-seq with CIBERSORT, and
      patient survival. RESULTS: Greater neoantigen burden and CD8+ T cell infiltration
      in primary, pre-treatment samples were independently associated with improved
      survival. Relapse samples collected after chemotherapy harbored a median of 78%
      more expressed neoantigens than untreated primary samples, a figure that combines
      the effects of chemotherapy and other processes operative during relapse. The
      contribution from chemotherapy-associated signatures was small, accounting for a
      mean of 5% (range 0-16) of the expressed neoantigen burden in relapse samples. In
      both treated and untreated samples, most neoantigens were attributed to COSMIC
      Signature (3), associated with BRCA disruption, Signature (1), associated with a
      slow mutagenic process active in healthy tissue, and Signature (8), of unknown
      etiology. CONCLUSION: Relapsed ovarian cancers harbor more predicted neoantigens
      than primary tumors, but the increase is due to pre-existing mutational
      processes, not mutagenesis from chemotherapy.

PMID- 29357824
TI  - A remarkable response to pazopanib, despite recurrent liver toxicity, in a
      patient with a high grade endometrial stromal sarcoma, a case report.
AB  - BACKGROUND: Pazopanib is an oral tyrosine kinase inhibitor registered for
      metastatic renal cell carcinoma and soft tissue sarcoma. Liver toxicity is a
      common side effect for this class of agents. The current opinion is that in case
      of severe liver toxicity pazopanib should be interrupted and restarted at a lower
      dose after returning to Common Terminology Criteria for Adverse Events (CTCAE)
      grade 1. After recurrence of liver toxicity at the lower dose it is advised to
      permanently stop pazopanib. We describe a patient with an YWHAE-FAM22
      translocated endometrial stromal sarcoma with a remarkable response to pazopanib
      despite recurrent liver toxicity. CASE PRESENTATION: A 40 year old woman was
      diagnosed with metastatic YWHAE-FAM22 translocated endometrial stromal sarcoma.
      She was treated successively with doxorubicin, megestrol acetate and anastrozole,
      before pazopanib was initiated. Several dose interruptions and reductions were
      necessary due to liver toxicity, but nevertheless she had a good partial
      response. Seven months after the start, pazopanib was permanently stopped because
      of a bilateral pneumothorax. Nine months later it was reinitiated because of
      progression and was continued for another 8 months until final disease
      progression. CONCLUSION: In contrast to the current summary of product
      characteristics of pazopanib, the drug was successfully continued despite
      recurrent liver toxicity, and no further liver function deterioration was found.
      This case suggests that further dose reductions are good practice when liver
      toxicity limits treatment in responding patients. Secondly, this patient with
      rare YWHAE-FAM22 translocated endometrial stromal sarcoma showed a remarkable
      response to VEGFR/KIT inhibitor pazopanib. Recently, it was reported that this
      specific subtype of endometrial stromal sarcoma overexpresses CD117, but has no
      KIT mutations. This case illustrates that (a) pazopanib can be continued in
      patients with recurrent liver toxicity after dose reductions under strict
      surveillance and that (b) pazopanib shows good efficacy in YWHAE-FAM22
      translocated endometrial stromal sarcoma.

PMID- 29357825
TI  - The walnut JrVHAG1 gene is involved in cadmium stress response through ABA-signal
      pathway and MYB transcription regulation.
AB  - BACKGROUND: Vacuolar H+-ATPase (V-ATPase) is a vital protein complex involved in
      abiotic stress response in plants. The G subunit of Juglans regia (JrVHAG1) was
      previously identified as a drought tolerance-related gene involved in the ABA
      (abscisic acid)-signal pathway. Heavy metal stress is becoming a major detriment
      for plant growth, development, and production. In order to understand the role of
      JrVHAG1, the potential function mechanism of JrVHAG1 exposed to CdCl2 stress was
      confirmed in this study. RESULTS: Transcription of JrVHAG1 was induced by ABA and
      increased to 58.89-fold (roots) and 7.38-fold (leaves) and by CdCl2 to 2.65-
      (roots) and 11.42-fold (leaves) relative to control, respectively. Moreover, when
      treated simultaneously with ABA and CdCl2 (ABA+CdCl2), JrVHAG1 was up-regulated
      to 110.13- as well as 165.42-fold relative to control in the roots and leaves,
      accordingly. Compared to the wild type (WT) Arabidopsis plants, the transgenic
      plants with overexpression of JrVHAG1 (G2, G6, and G9) exhibited increased seed
      germination rate, biomass accumulation, proline content, and activities of
      superoxide dismutase (SOD) and peroxidase (POD) under ABA, CdCl2, and ABA+CdCl2
      treatments. In contrast, the reactive oxygen species (ROS) staining,
      malondialdehyde (MDA) content, hydrogen dioxide (H2O2) content, as well as
      electrolyte leakage (EL) rates of transgenic seedlings were all lower than those
      of WT exposed to ABA, CdCl2 and ABA+CdCl2 stresses. Furthermore, a 1200 bp
      promoter fragment of JrVHAG1 was isolated by analyzing the genome of J. regia, in
      which the cis-elements were identified. This JrVHAG1 promoter fragment showed
      expression activity that was enhanced significantly when subjected to the above
      treatments. Yeast one-hybrid assay and transient expression analysis demonstrated
      that JrMYB2 specifically bound to the MYBCORE motif and shared similar expression
      patterns with JrVHAG1 under ABA, CdCl2 and ABA+CdCl2 stress conditions.
      CONCLUSIONS: Our results suggested that the JrVHAG1 gene functions as a CdCl2
      stress response regulator by participating in ABA-signal pathway and MYB
      transcription regulation network. JrVHAG1 gene is a useful candidate gene for
      heavy metal stress tolerance in plant molecular breeding.

PMID- 29357826
TI  - Effects of resistance training on body composition and functional capacity among
      sarcopenic obese residents in long-term care facilities: a preliminary study.
AB  - BACKGROUND: Aging-related loss of muscle and strength with increased adiposity is
      prevalent among older people in long-term care (LTC) facilities. Studies have
      shown that people with sarcopenic obesity (SO) are at high risk of declining
      physical performance. At present, no interventional studies on residents with SO
      in nursing homes have been conducted in the literature. The objectives of this
      study include appraising the changes in body composition and physical performance
      following resistance training among residents with SO in LTC facilities. METHODS:
      This study used a quasiexperimental research design. Residents who are 60 years
      of age or above and have been living a sedentary lifestyle in LTC facilities for
      the past 3 months will be eligible for inclusion. The intervention group engaged
      in chair muscle strength training twice a week for 12 weeks, whereas the control
      group underwent the usual care. The main variables were physical parameters of
      being lean and fat, the strength of grip and pinch, and a functional independence
      measure using descriptive analysis, chi-squared test, t-test, and generalized
      estimating equation for statistical analysis through SPSS. RESULTS: A total of 64
      respondents with SO completed the study. After training, total grip strength (p =
      0.001) and total pinch strength (p = 0.014) of the intervention group differed
      significantly from those of the control group. The right grip strength of the
      intervention group increased by 1.71 kg (p = 0.003) and the left grip strength
      improved by 1.35 kg (p = 0.028) compared with baseline values. The self-care
      scores of the intervention group increased by 2.76 points over baseline scores,
      particularly for the action of dressing oneself. Although grip strength and self
      care scores improved more among those in the intervention group, body fat and
      skeletal muscle percentages did not differ significantly between the groups after
      training (p > 0.05). CONCLUSIONS: Resistance exercises for elderly residents in
      LTC facilities may play an important role in helping them maintain physical well
      being and improve muscle strength. TRIAL REGISTRATION: Clinicaltrials.gov, number
      NCT02912338 . Retrospectively registered on 09/21/2016.

PMID- 29357828
TI  - Birt-Hogg-Dube syndrome in two Chinese families with mutations in the FLCN gene.
AB  - BACKGROUND: Birt-Hogg-Dube syndrome is an autosomal dominant hereditary condition
      caused by mutations in the folliculin-encoding gene FLCN (NM_144997). It is
      associated with skin lesions such as fibrofolliculoma, acrochordon and
      trichodiscoma; pulmonary lesions including spontaneous pneumothorax and pulmonary
      cysts and renal cancer. METHODS: Genomic DNA was extracted from peripheral venous
      blood samples of the propositi and their family members. Genetic analysis was
      performed by whole exome sequencing and Sanger sequencing aiming at corresponding
      exons in FLCN gene to explore the genetic mutations of these two families.
      RESULTS: In this study, we performed genetic analysis by whole exome sequencing
      and Sanger sequencing aiming at corresponding exons in FLCN gene to explore the
      genetic mutations in two Chinese families. Patients from family 1 mostly suffered
      from pneumothorax and pulmonary cysts, several of whom also mentioned skin
      lesions or kidney lesions. While in family 2, only thoracic lesions were found in
      the patients, without any other clinical manifestations. Two FLCN mutations have
      been identified: One is an insertion mutation (c.1579_1580insA/p.R527Xfs on exon
      14) previously reported in three Asian families (one mainland family and two
      Taiwanese families); while the other is a firstly reviewed mutation in Asian
      population (c.649C > T / p.Gln217X on exon 7) that ever been detected in a French
      family. CONCLUSIONS: Overall, The detection of these two mutations expands the
      spectrum of FLCN mutations and will provide insight into genetic diagnosis and
      counseling of Birt-Hogg-Dube syndrome.

PMID- 29357827
TI  - Transcriptomic analysis reveals unique molecular factors for lipid hydrolysis,
      secondary cell-walls and oxidative protection associated with thermotolerance in
      perennial grass.
AB  - BACKGROUND: Heat stress is the primary abiotic stress limiting growth of cool
      season grass species. The objective of this study was to determine molecular
      factors and metabolic pathways associated with superior heat tolerance in thermal
      bentgrass (Agrostis scabra) by comparative analysis of transcriptomic profiles
      with its co-generic heat-sensitive species creeping bentgrass (A. stolonifera).
      RESULTS: Transcriptomic profiling by RNA-seq in both heat-sensitive A.
      stolonifera (cv. 'Penncross') and heat-tolerant A. scabra exposed to heat stress
      found 1393 (675 up- and 718 down-regulated) and 1508 (777 up- and 731 down
      regulated) differentially-expressed genes, respectively. The superior heat
      tolerance in A. scabra was associated with more up-regulation of genes in
      oxidative protection, proline biosynthesis, lipid hydrolysis, hemicellulose and
      lignin biosynthesis, compared to heat-sensitive A. stolonifera. Several
      transcriptional factors (TFs), such as high mobility group B protein 7 (HMGB7),
      dehydration-responsive element-binding factor 1a (DREB1a), multiprotein-bridging
      factor 1c (MBF1c), CCCH-domain containing protein 47 (CCCH47), were also found to
      be up-regulated in A. scabra under heat stress. CONCLUSIONS: The unique TFs and
      genes identified in thermal A. scabra could be potential candidate genes for
      genetic modification of cultivated grass species for improving heat tolerance,
      and the associated pathways could contribute to the transcriptional regulation
      for superior heat tolerance in bentgrass species.

PMID- 29357829
TI  - Caffeine is a risk factor for osteopenia of prematurity in preterm infants: a
      cohort study.
AB  - BACKGROUND: Caffeine, the most commonly used medication in Neonatal Intensive
      Care Units, has calciuric and osteoclastogenic effects. METHODS: To examine the
      association between the cumulative dose and duration of therapy of caffeine and
      osteopenia of prematurity, a retrospective cohort study was conducted including
      premature infants less than 31 weeks and birth weight less than 1500 g.
      Osteopenia of prematurity was evaluated using chest X-rays on a biweekly basis
      over 12 weeks of hospitalization. RESULTS: The cohort included 109 infants. 51%
      had osteopenia of prematurity and 8% had spontaneous rib fractures. Using the
      generalized linear mixed model, caffeine dose and duration of caffeine therapy
      showed a strong association with osteopenia of prematurity. Steroids and vitamin
      D were also significantly correlated with osteopenia of prematurity while
      diuretic use did not show a statistically significant effect. CONCLUSION: The
      cumulative dose and duration of therapy of caffeine, as well as steroid are
      associated with osteopenia of prematurity in this cohort. Future studies are
      needed to confirm these findings and determine the lowest dose of caffeine needed
      to treat effectively apnea of prematurity.

PMID- 29357831
TI  - The necessity and optimal time for performing pars plana vitrectomy in acute
      retinal necrosis patients.
AB  - BACKGROUND: To compare the efficacy of pars plana vitrectomy (PPV) at different
      time points to treat acute retinal necrosis (ARN) and to investigate the
      necessity of PPV for ARN. METHODS: A retrospective review of the treatment
      options and outcomes of the ARN patients was performed. Thirty ARN patients (34
      eyes) were included in this study. The eyes were divided into 3 groups depending
      on the treatment administered. In the medically treated group, there was no
      retinal detachment (RD) at the first visit. The routine group patients were
      treated with systemic antiviral medications, as well as with intravitreal
      antiviral injections. In the early PPV treatment group, there was no RD at the
      first visit. The early PPV treatment group patients were treated with systemic
      antiviral medications and PPV plus silicone oil tamponade and intravitreal
      injection. In the PPV group, there was RD at the first visit. The PPV group
      patients were treated with systemic antiviral medications and PPV plus silicone
      oil tamponade and intravitreal injection. RESULTS: In the medically treated
      group, the mean baseline best corrected visual acuity (BCVA) (logMAR) was 1.38 +/
      0.35. The BCVA was 1.21 +/- 0.36 at the last visit for the medically treated
      group. In this group, one eye (12.5%) developed RD after 1 month of treatment. In
      the early PPV treatment group, the mean BCVA (logMAR) was 1.68 +/- 0.26. The BCVA
      was 1.83 +/- 0.21 at the last visit for the early PPV group. In this group, five
      eyes (29.4%) had recurrent RD before silicone oil removal. In the PPV group, the
      mean BCVA (logMAR) was 2.0 +/- 0.35. The BCVA was 1.72 +/- 0.34 at the last visit
      for the PPV group. In this group, one eye (11.1%) had recurrent RD before
      silicone oil removal. There were no significant differences among the three
      groups in the baseline BCVA and the BCVA at the last visit (p>0.05). There were
      no significant differences between the early PPV group and the PPV group in the
      recurrent RD rates (p = 0.38). CONCLUSIONS: Prophylactic PPV showed no difference
      in recurrent RD rates or better BCVA. Therefore, prophylactic vitrectomy cannot
      prevent RD nor improve the prognosis of ARN based on our research.

PMID- 29357830
TI  - Nicotine dependence in Croatian male inpatients with schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia have the highest known rates of cigarette
      smoking, but less is known about their smoking behavior and the differences
      across geographical regions, including Croatia. The aim of this study was to
      compare patterns of nicotine dependence between patients with schizophrenia and
      healthy individuals, and to determine the relationship between clinical
      presentation and the severity of smoking. METHODS: This cross-sectional study
      included 182 recently hospitalized male inpatients and 280 healthy males, who
      were daily smokers. All participants have fulfilled the Fagerstrom Test for
      Nicotine Dependence (FTND). Patients were also evaluated by the Positive and
      Negative Syndrome Scale (PANSS). RESULTS: Patients had higher FTND total score (p
      = 0.010), smoked their first cigarette earlier in the morning (p = 0.000),
      consumed higher number of cigarettes (p = 0.000), while healthy subjects had more
      difficulties to refrain from smoking in places where it is forbidden (p = 0.000)
      and smoked more even when they were sick (p = 0.000). While severe dependence was
      more prevalent in the patient group, light dependence was more frequent in
      control subjects (p = 0.04). Smoking behavior was not associated with either
      PANSS total score or any of its subscales and items. CONCLUSIONS: Smokers with
      schizophrenia differ from healthy smokers in both smoking behavior and level of
      dependence. Longitudinal studies are needed to shed more light on the complex
      relationship between smoking and psychopathology in schizophrenia.

PMID- 29357832
TI  - DArT, SNP, and SSR analyses of genetic diversity in Lolium perenne L. using bulk
      sampling.
AB  - BACKGROUND: Lolium perenne L. is the most important forage grass species in
      temperate regions. It is also considered as a sustainable source of biomass for
      energy production. However, improvement in biomass yield has been limited by
      comparison with other major crops. More efficient utilisation of genetic
      resources and improved breeding schemes are required to advance L. perenne
      breeding. In an attempt to elucidate the extent of genetic diversity in L.
      perenne, 1384 DArT, 182 SNP and 48 SSR markers were applied to 297 accessions
      (Set I) contributed by three German breeding companies and the IPK Genebank. Due
      to the heterogeneous nature of Lolium accessions, bulk samples were used. Apart
      from germplasm set I, additional set II and set III was used to determine the
      reproducibility of marker system and judge the feasibility of bulk strategy in
      this study. RESULTS: By assessing different bulk sizes, 24 individuals per sample
      were shown to be a representative number of plants to discriminate different
      accessions. Among the 297 accessions, all marker types revealed a high
      polymorphism rate; 1.99, 2.00 and 8.19 alleles, were obtained per locus on
      average using DArTs, SNPs and SSRs, respectively. The Jaccard distance for DArT
      markers ranged from 0.00 to 0.73, the Modified Roger's distance (MRD) for SNP
      markers ranged from 0.03 to 0.52, and for SSR markers from 0.26 to 0.76. Gene
      diversity for dominant DArT and co-dominant SNP and SSR markers was found to be
      0.26, 0.32 and 0.45, respectively. DArT markers showed the highest consistency
      and reproducibility. CONCLUSION: The resulting data were evaluated using a number
      of different classification methods, but none of the methods showed a clear
      differentiation into distinct genetic pools. With regard to hybrid breeding, this
      will possibly impede substantial progress towards increased biomass yields of L.
      perenne by utilising heterosis.

PMID- 29357833
TI  - Genome-wide DNA methylation profiling in whole blood reveals epigenetic
      signatures associated with migraine.
AB  - BACKGROUND: Migraine is a common heritable neurovascular disorder typically
      characterised by episodic attacks of severe pulsating headache and nausea, often
      accompanied by visual, auditory or other sensory symptoms. Although genome-wide
      association studies have identified over 40 single nucleotide polymorphisms
      associated with migraine, there remains uncertainty about the casual genes
      involved in disease pathogenesis and how their function is regulated. RESULTS: We
      performed an epigenome-wide association study, quantifying genome-wide patterns
      of DNA methylation in 67 migraine cases and 67 controls with a matching age and
      sex distribution. Association analyses between migraine and methylation probe
      expression, after adjustment for cell type proportions, indicated an excess of
      small P values, but there was no significant single-probe association after
      correction for multiple testing (P < 1.09 * 10- 7). However, utilising a 1 kb
      sliding window approach to combine adjacent migraine-methylation association P
      values, we identified 62 independent differentially methylated regions (DMRs)
      underlying migraine (false discovery rate < 0.05). Migraine association signals
      were subtle but consistent in effect direction across the length of each DMR.
      Subsequent analyses showed that the migraine-associated DMRs were enriched in
      regulatory elements of the genome and were in close proximity to genes involved
      in solute transportation and haemostasis. CONCLUSIONS: This study represents the
      first genome-wide analysis of DNA methylation in migraine. We have identified DNA
      methylation in the whole blood of subjects associated with migraine, highlighting
      novel loci that provide insight into the biological pathways and mechanisms
      underlying migraine pathogenesis.

PMID- 29357834
TI  - Revealing the selection history of adaptive loci using genome-wide scans for
      selection: an example from domestic sheep.
AB  - BACKGROUND: One of the approaches to detect genetics variants affecting fitness
      traits is to identify their surrounding genomic signatures of past selection.
      With established methods for detecting selection signatures and the current and
      future availability of large datasets, such studies should have the power to not
      only detect these signatures but also to infer their selective histories.
      Domesticated animals offer a powerful model for these approaches as they adapted
      rapidly to environmental and human-mediated constraints in a relatively short
      time. We investigated this question by studying a large dataset of 542
      individuals from 27 domestic sheep populations raised in France, genotyped for
      more than 500,000 SNPs. RESULTS: Population structure analysis revealed that this
      set of populations harbour a large part of European sheep diversity in a small
      geographical area, offering a powerful model for the study of adaptation.
      Identification of extreme SNP and haplotype frequency differences between
      populations listed 126 genomic regions likely affected by selection. These
      signatures revealed selection at loci commonly identified as selection targets in
      many species ("selection hotspots") including ABCG2, LCORL/NCAPG, MSTN, and coat
      colour genes such as ASIP, MC1R, MITF, and TYRP1. For one of these regions
      (ABCG2, LCORL/NCAPG), we could propose a historical scenario leading to the
      introgression of an adaptive allele into a new genetic background. Among
      selection signatures, we found clear evidence for parallel selection events in
      different genetic backgrounds, most likely for different mutations. We confirmed
      this allelic heterogeneity in one case by resequencing the MC1R gene in three
      black-faced breeds. CONCLUSIONS: Our study illustrates how dense genetic data in
      multiple populations allows the deciphering of evolutionary history of
      populations and of their adaptive mutations.

PMID- 29357835
TI  - Factors associated with mental health consultation in South Korea.
AB  - BACKGROUND: The aim of this study was to examine factors associated with the use
      of mental health consultation for depressive symptoms. METHODS: We used data from
      the 2013 Community Health Survey, which included responses from 13,269
      individuals who reported that they had experienced depressive symptoms for more
      than 2 weeks in Korea. We investigated associations between mental health
      consultation rates for depressive symptoms and sociodemographic, socioeconomic,
      and health-related factors. Logistic regression analysis was used to examine the
      significance of associations. RESULTS: Among participants who report depressive
      symptoms, 16.0% (n = 2120) undergo mental health consultation. Respondents with a
      college education or over are more likely to undergo mental health consultation
      (odds ratio (OR) = 1.49; 95% CI: 1.21-1.84) than respondents with less education.
      Individuals aged 70 years or above are less likely to receive mental health
      consultation than those aged between 19 and 29 years. Females exhibit higher
      mental health consultation rates than males. Respondents who are divorced show
      greater odds of receiving mental health consultation than respondents who are
      married and cohabitate with their spouse. CONCLUSIONS: This study indicates that
      rates of use of mental health consultation services are lower among older adults
      and men and higher among divorced people. Educational level shows a significant
      positive association with mental health consultation among Koreans. The results
      could have implications for mental health policy in many ways in Korea.

PMID- 29357836
TI  - Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker
      in clear cell renal cell carcinoma.
AB  - BACKGROUND: Scavenger receptor class B type I (SR-BI) has been reported to be
      involved in carcinogenesis of several human cancers. However, it is currently
      unknown whether SR-BI plays a role in clear cell renal cell carcinoma (ccRCC).
      Here, we aimed to evaluate a tumor promotive mechanism for SR-BI in ccRCC.
      METHODS: The expression of SR-BI was evaluated by real-time quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), Western blot and
      immunohistochemistry (IHC) in ccRCC tissues and cell lines. Lipid droplets in
      ccRCC tissues and normal kidney tissues were examined by Oil Red O (ORO) and
      hematoxylin-eosin (HE) staining. The correlation between SR-BI mRNA levels and
      clinicopathological features was analyzed by Pearson's chi-square test or
      Fisher's exact test. Kaplan-Meier analysis and Cox model were used to evaluate
      the difference in progression-free survival (PFS) associated with expression of
      SR-BI. Inhibition of SR-BI was conducted by using small interfering RNA (siRNA).
      In vitro assays were performed to assess the impact of SR-BI knockdown on cell
      biological behaviors. High density lipoprotein (HDL)-cholesterol content in ccRCC
      cells and extracellular media was also measured after transfection with siRNA.
      RESULTS: The expression of SR-BI was markedly up-regulated in ccRCC tissues and
      tumor cell lines. ORO and HE staining revealed huge amounts of lipid droplets
      accumulation in ccRCC. Clinical analysis showed that over-expression of SR-BI was
      positively associated with tumor size, grade, distant metastasis and inversely
      correlated with PFS. Furthermore, SR-BI was proved to be an independent
      prognostic marker in ccRCC patients. The inhibition of SR-BI attenuated the
      tumorous behaviors of ccRCC cells, expression of metastasis and AKT pathway
      related proteins. The content of HDL-cholesterol was reduced in cells while
      increased in extracellular media after transfection with si-SR-BI. CONCLUSIONS:
      Our results demonstrate that SR-BI functions as an oncogene and promotes
      progression of ccRCC. SR-BI may serve as a potential prognostic biomarker and
      therapeutic target for ccRCC.

PMID- 29357837
TI  - Detecting TF-miRNA-gene network based modules for 5hmC and 5mC brain samples: a
      intra- and inter-species case-study between human and rhesus.
AB  - BACKGROUND: Study of epigenetics is currently a high-impact research topic. Multi
      stage methylation is also an area of high-dimensional prospect. In this article,
      we provide a new study (intra and inter-species study) on brain tissue between
      human and rhesus on two methylation cytosine variants based data-profiles (viz.,
      5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) samples) through TF
      miRNA-gene network based module detection. RESULTS: First of all, we determine
      differentially 5hmC methylated genes for human as well as rhesus for intra
      species analysis, and differentially multi-stage methylated genes for inter
      species analysis. Thereafter, we utilize weighted topological overlap matrix
      (TOM) measure and average linkage clustering consecutively on these genesets for
      intra- and inter-species study.We identify co-methylated and multi-stage co
      methylated gene modules by using dynamic tree cut, for intra-and inter-species
      cases, respectively. Each module is represented by individual color in the
      dendrogram. Gene Ontology and KEGG pathway based analysis are then performed to
      identify biological functionalities of the identified modules. Finally, top ten
      regulator TFs and targeter miRNAs that are associated with the maximum number of
      gene modules, are determined for both intra-and inter-species analysis.
      CONCLUSIONS: The novel TFs and miRNAs obtained from the analysis are: MYST3 and
      ZNF771 as TFs (for human intra-species analysis), BAZ2B, RCOR3 and ATF1 as TFs
      (for rhesus intra-species analysis), and mml-miR-768-3p and mml-miR-561 as miRs
      (for rhesus intra-species analysis); and MYST3 and ZNF771 as miRs(for inter
      species study). Furthermore, the genes/TFs/miRNAs that are already found to be
      liable for several brain-related dreadful diseases as well as rare neglected
      diseases (e.g., wolf Hirschhorn syndrome, Joubarts Syndrome, Huntington's
      disease, Simian Immunodeficiency Virus(SIV) mediated enchaphilits, Parkinsons
      Disease, Bipolar disorder and Schizophenia etc.) are mentioned.

PMID- 29357838
TI  - AZGP1 inhibits soft tissue sarcoma cells invasion and migration.
AB  - BACKGROUND: One of the major challenges in soft tissue sarcomas is to identify
      factors that predict metastasis. AZGP1 is a potential biomarker of cancer
      progression, but its value in soft tissue sarcomas remains unknown. The aim of
      this study is to determine the expression level of AZGP1 in soft tissue sarcomas,
      and to analyze its influence on tumor progression. METHODS: AZGP1
      immunohistochemistry (IHC) and RT-PCR were performed in 86 patients with soft
      tissue sarcomas. The relationships between AZGP1 levels and clinicopathologic
      features were analyzed. In vitro experiments were performed using fibrosarcoma
      (HT1080), rhabdomyosarcoma (RD) and synovial sarcoma (SW982) cell lines to
      corroborate our findings. We used lentiviral over-expression and knockdown assays
      to examine how changes of AZGP1 expressions might affect cellular migration and
      invasion. RESULTS: The quantitative RT-PCR results showed that AZGP1 expression
      was negatively correlated with metastasis and overall survival in soft tissue
      sarcomas (p < 0.05). Immunohistochemical staining showed lower expression of
      AZGP1 in patients with metastasis than in those without. Kaplan-Meier survival
      analysis showed that patients with low expression of AZGP1 had shorter overall (p
      = 0.056) and metastasis-free survivals (p = 0.038). These findings were
      corroborated by our in vitro experiments. Over-expression of AZGP1 significantly
      decreased RD cellular migration and invasion by 64% and 78%, respectively. HT1080
      cells migration was inhibited by 2-fold, whereas their invasion was repressed by
      7-fold after AZGP1 knockdown. CONCLUSIONS: Our study reveals that reduced AZGP1
      expression correlates with in vitro cellular migration and invasion. In vivo, it
      is associated with higher metastatic risk and shorter survival in patients with
      soft tissue sarcomas.

PMID- 29357839
TI  - Orbital sparganosis in an 8-year boy: a case report.
AB  - BACKGROUND: Sparganosis is one of the neglected but important food-borne
      parasitic zoonoses, with higher prevalence in Asian countries. The infection is
      commonly located in the subcutaneous tissue, brain, breast, and lung, but fewer
      reported infections involve the eye. Because the majority of patients with
      sparganosis are adults, it is likely to be missed in children. CASE PRESENTATION:
      An 8-year-old boy presented to our clinic complaining of a painless ocular mass
      in his right eye for 1 month. The boy had a history of eating frogs and frog
      poultice applications to his eyelids. The patient was checked for an elliptical
      mass near the medial wall of the right eye. Serodiagnosis testing was positive in
      an enzyme-linked immunosorbent assay. During surgical operation on the patient,
      calcified parasite eggs and foreign body granulomatous reaction were found using
      histological examination. Due to early detection and surgery, the patient fully
      recovered with no damage to his eyesight. CONCLUSIONS: Although rare, ocular
      sparganosis should be suspected in a mass of the eye when there is a history of
      eating frogs and frog poultice applications on eyelids. Early surgical resection
      is important for a good prognosis.

PMID- 29357840
TI  - FAM3B/PANDER inhibits cell death and increases prostate tumor growth by
      modulating the expression of Bcl-2 and Bcl-XL cell survival genes.
AB  - BACKGROUND: FAM3B/PANDER is a novel cytokine-like protein that induces apoptosis
      in insulin-secreting beta-cells. Since in silico data revealed that FAM3B can be
      expressed in prostate tumors, we evaluated the putative role of this cytokine in
      prostate tumor progression. METHODS: FAM3B expression was analyzed by
      quantitative PCR in tumor tissue clinical samples and prostate tumor cell lines.
      Culture growth and viability of DU145 cell line were evaluated after treatment
      with either exogenous FAM3B protein obtained from conditioned media (CM) of 293 T
      cells overexpressing FAM3B or a recombinant FAM3B protein produced in a bacterial
      host. DU145 cells overexpressing FAM3B protein were produced by lentiviral
      mediated transduction of full-length FAM3B cDNA. Cell viability and apoptosis
      were analyzed in DU145/FAM3B cells after treatment with several cell death
      inducers, such as TNF-alpha, staurosporine, etoposide, camptothecin, and serum
      starvation conditions. Anchorage-independent growth in soft agarose assay was
      used to evaluate in vitro tumorigenicity. In vivo tumorigenicity and invasiveness
      were evaluated by tumor xenograft growth in nude mice. RESULTS: We observed an
      increase in FAM3B expression in prostate tumor samples when compared to normal
      tissues. DU145 cell viability and survival increased after exogenous treatment
      with recombinant FAM3B protein or FAM3B-secreted protein. Overexpression of FAM3B
      in DU145 cells promoted inhibition of DNA fragmentation and phosphatidylserine
      externalization in a time and dose-dependent fashion, upon apoptosis triggered by
      TNF-alpha. These events were accompanied by increased gene expression of anti
      apoptotic Bcl-2 and Bcl-XL, decreased expression of pro-apoptotic Bax and
      diminished caspase-3, -8 and -9 proteolytic activities. Furthermore, inhibition
      of Bcl-2 anti-apoptotic family proteins with small molecules antagonists
      decreases protective effects of FAM3B in DU145 cells. When compared to the
      respective controls, cells overexpressing FAM3B displayed a decreased anchorage-
      independent growth in vitro and increased tumor growth in xenografted nude mice.
      The immunohistochemistry analysis of tumor xenografts revealed a similar anti
      apoptotic phenotype displayed by FAM3B-overexpressing tumor cells. CONCLUSIONS:
      Taken together, by activating pro-survival mechanisms FAM3B overexpression
      contributes to increased resistance to cell death and tumor growth in nude mice,
      highlighting a putative role for this cytokine in prostate cancer progression.

PMID- 29357842
TI  - Breast magnetic resonance imaging for surveillance of women with a personal
      history of breast cancer: outcomes stratified by interval between definitive
      surgery and surveillance MR imaging.
AB  - BACKGROUND: Women with a personal history of breast cancer are at increased risk
      of future breast cancer events, and may benefit from supplemental screening
      methods that could enhance early detection of subclinical disease. However,
      current literature on breast magnetic resonance (MR) imaging surveillance is
      limited. We investigated outcomes of surveillance breast magnetic resonance (MR)
      imaging in women with a personal history of breast cancer. METHODS: We reviewed
      1053 consecutive breast MR examinations that were performed for surveillance in
      1044 women (median age, 53 years; range, 20-85 years) previously treated for
      breast cancer between August 2014 and February 2016. All patients had previously
      received supplemental surveillance with ultrasound. Cancer detection rate (CDR),
      abnormal interpretation rate and characteristics of MR-detected cancers were
      assessed, including extramammary cancers. We also calculated the PPV 1 , PPV 3 ,
      sensitivity and specificity for MR-detected intramammary lesions. Performance
      statistics were stratified by interval following initial surgery. RESULTS: The
      CDR for MR-detected cancers was 6.7 per 1000 examinations (7 of 1053) and was 3.8
      per 1000 examinations (4 of 1053) for intramammary cancers. The overall abnormal
      interpretation rate was 8.0%, and the abnormal interpretation rate for
      intramammary lesions was 7.2%. The PPV1, PPV3, sensitivity and specificity for
      intramammary lesions was 5.3% (4 of 76), 15.8% (3 of 19), 75.0% (3 of 4) and
      98.3% (1031 of 1049), respectively. For MR examinations performed <=36 months
      after surgery, the overall CDR was 1.4 per 1000 examinations. For MR examinations
      performed > 36 months after surgery, the overall CDR was 17.4 per 1000
      examinations. CONCLUSIONS: Surveillance breast MR imaging may be considered in
      women with a history of breast cancer, considering the low abnormal
      interpretation rate and its high specificity. However, the cancer detection rate
      was low and implementation may be more effective after more than 3 years after
      surgery.

PMID- 29357841
TI  - Study on the persistence of Zika virus (ZIKV) in body fluids of patients with
      ZIKV infection in Brazil.
AB  - BACKGROUND: Zika virus (ZIKV) has been identified in several body fluids of
      infected individuals. In most cases, it remained detected in blood from few days
      to 1 week after the onset of symptoms, and can persist longer in urine and in
      semen. ZIKV infection can have dramatic consequences such as microcephaly and
      Guillain-Barre syndrome. ZIKV sexual transmission has been documented. A better
      understanding of ZIKV presence and persistence across biologic compartments is
      needed to devise rational measures to prevent its transmission. METHODS: This
      observational cohort study will recruit non-pregnant participants aged 18 years
      and above with confirmed ZIKV infection [positive reverse transcriptase
      polymerase chain reaction (RT-PCR) test in blood and/or urine]: symptomatic men
      and women in ZIKV infection acute phase, and their symptomatic or asymptomatic
      household/sexual infected contacts. Specimens of blood, urine, semen, vaginal
      secretion/menstrual blood, rectal swab, oral fluids, tears, sweat, urine and
      breast milk (if applicable) will be collected at pre-established intervals and
      tested for ZIKV RNA presence by RT-PCR, other co-infection (dengue, Chikungunya,
      HIV, hepatitis B and C, syphilis), antibody response (including immunoglobulins M
      and G), plaque reduction neutralization test (if simultaneously positive for ZIKV
      and dengue), and ZIKV culture and RNA sequencing. Data on socio-demographic
      characteristics and comorbidities will be collected in parallel. Participants
      will be followed up for 12 months. DISCUSSION: This prolonged longitudinal follow
      up of ZIKV infected persons with regular biologic testing and data collection
      will offer a unique opportunity to investigate the presence and persistence of
      ZIKV in various biologic compartments, their clinical and immunological
      correlates as well as the possibility of ZIKV reactivation/reinfection over time.
      This valuable information will substantially contribute to the body of knowledge
      on ZIKV infection and serve as a base for the development of more effective
      recommendation on the prevention of ZIKV transmission. TRIAL REGISTRATION:
      NCT03106714 . Registration Date: April, 7, 2017.

PMID- 29357843
TI  - An individually randomized controlled trial to determine the effectiveness of the
      Women for Women International Programme in reducing intimate partner violence and
      strengthening livelihoods amongst women in Afghanistan: trial design, methods and
      baseline findings.
AB  - BACKGROUND: Intimate Partner Violence (IPV) is the most common form of violence
      in conflict and post-conflict settings, but there are few evaluations of
      interventions to prevent IPV in such settings. METHODS: The Women for Women
      International (WfWI) intervention is a year-long combined economic and social
      empowerment intervention for marginalized women survivors of conflict. Primarily,
      it seeks to support women to achieve four key outcomes: women earn and save
      money; women improve their health and well-being; women influence decisions in
      their homes and communities; women connect to networks for support. The
      organization recognizes Violence Against Women and Girls (VAWG) as a significant
      barrier to women's empowerment and expects to see reduction in VAWG, and
      specifically IPV, as part of building women's social and economic empowerment.
      This program is being quantitatively evaluated through an individually randomized
      control trial amongst women in Afghanistan, with a 24-month follow up. A
      comparison of baseline characteristics of participants is also included as well
      as a discussion of implementation of the baseline research. DISCUSSION: There is
      a high demand amongst Afghan women for such interventions, and this posed
      challenges in completing the randomization and baseline. In addition, the complex
      security situation in Afghanistan also posed challenges. However, despite these
      issues, recruitment was successfully achieved and the arms were balanced on socio
      demographic measures. The evaluation will contribute to the limited evidence base
      on interventions to prevent IPV in conflict-affected settings. TRIAL
      REGISTRATION: NCT03236948 . Registered 28 July 2017, retrospectively registered.

PMID- 29357845
TI  - Dairy product consumption and risk of hip fracture: a systematic review and meta
      analysis.
AB  - BACKGROUND: Dairy product consumption may affect the risk of hip fracture, but
      previous studies have reported inconsistent findings. The primary aim of our meta
      analysis was to examine and quantify the potential association of dairy product
      consumption with risk of hip fracture. METHODS: We searched the databases of
      PubMed and EMBASE for relevant articles from their inception through April 17,
      2017. The final analysis included 10 cohort studies and 8 case-control studies.
      Random-effects models were used to estimate the pooled risk. Subgroup and dose
      response analyses were conducted to explore the relationships between the
      consumption of milk and the risk of hip fracture. RESULTS: After pooling the data
      from the included studies, the summary relative risk (RR) for hip fracture for
      highest versus lowest consumption were 0.91 (95% CI: 0.74-1.12), 0.75 (95% CI:
      0.66-0.86), 0.68 (95% CI: 0.61-0. 77), 1.02 (95% CI: 0.93-1.12) for milk, yogurt,
      cheese, and total dairy products in cohort studies, respectively. Higher milk
      consumption [Odds ratio (OR), 0.71, 95% CI: 0.55-0. 91] was associated with lower
      risk of hip fracture for highest versus lowest consumption in case-control
      studies. After quantifying the specific dose of milk, the summary RR/OR for an
      increased milk consumption of 200 g/day was 1.00 (95% CI: 0.94-1.07), and 0.89
      (95%CI: 0.64-1.24) with significant heterogeneity for cohort and case-control
      studies, respectively; There was a nonlinear association between milk consumption
      and hip fracture risk in cohort, and case-control studies. CONCLUSIONS: Our
      findings indicate that consumption of yogurt and cheese was associated with lower
      risk of hip fracture in cohort studies. However, the consumption of total dairy
      products and cream was not significantly associated with the risk of hip
      fracture. There was insufficient evidence to deduce the association between milk
      consumption and risk of hip fracture. A lower threshold of 200 g/day milk intake
      may have beneficial effects, whereas the effects of a higher threshold of milk
      intake are unclear.

PMID- 29357844
TI  - With axial loading during MRI diurnal T2-value changes in lumbar discs are
      neglectable: a cross sectional study.
AB  - BACKGROUND: Axial loading during MRI (alMRI) combined with T2 mapping recently
      was shown as a promising method to reveal biomechanical intervertebral disc (IVD)
      characteristics. This feasibility study aims to investigate whether there is a
      diurnal variation in the IVD T2-value when using alMRI. This is of importance for
      the planning of when to perform alMRI investigations and for interpretations of
      alMRI findings in relation to clinical symptoms. METHODS: Six healthy volunteers
      (30 lumbar discs), were examined with alMRI at three different sessions during 1
      day. To be representative for a low back pain cohort in terms of age and IVD
      degeneration the included participants had a wide age range (27-63y) and all
      Pfirrmann grades represented. The T2-values were measured in five IVD regions of
      interest (ROI). The ROIs were equally large in sagittal plane with ROI1
      representing anterior parts of the IVD, ROI5 posterior IVD parts and ROI2-4 the
      parts in between. RESULTS: T2-values of the entire IVD varied between 38 and 138
      ms at 7 am, 33-143 ms at 11.30 am, and 31-147 ms at 4 pm with large regional IVD
      variations at all time points. No significant alterations of the T2-values over
      the day were found, neither for the entire IVD (p = 0.4) nor for the various ROIs
      (p = 0.2-1.0). Neither when correlated to Pfirrmann grade, any significant
      diurnal T2-value changes were found. CONCLUSIONS: With alMRI, only minor diurnal
      T2-value changes were found in the lumbar discs. Nonsignificant and neglectable
      diurnal changes are advantageous both for research purposes, as well as in the
      clinical setting, giving comparable and robust data regardless of at what time
      point the alMRI is performed.

PMID- 29357846
TI  - Neoboutonia melleri var velutina Prain: in vitro and in vivo hepatoprotective
      effects of the aqueous stem bark extract on acute hepatitis models.
AB  - BACKGROUND: Hepatitis is a liver inflammation caused by different agents and
      remains a public health problem worldwide. Medicinal plants are an important
      source of new molecules being considered for treatment of this disease. Our work
      aims at evaluating the hepatoprotective properties of Neoboutonia velutina, a
      Cameroonian medicinal plant. METHODS: The aqueous extract has been prepared using
      phytochemical methods. HepG2 cells were used to assess anti-inflammatory
      properties of the extract at different concentrations. Acute hepatitis models
      (Carbon tetrachloride and Concanavalin A) were performed in mice receiving or not
      receiving, different extract doses by gavage. Liver injury was assessed using
      histology, transaminases and pro-inflammatory markers. Extract antioxidant and
      radical scavenging capacities were evaluated. RESULTS: The extract led to a
      significant decrease in pro-inflammatory cytokine expression in vitro and to a
      remarkable protection of mice from carbon tetrachloride-induced liver injury, as
      shown by a significant decrease in dose-dependent transaminases level. Upon
      extract treatment, inflammatory markers were significantly decreased and liver
      injuries were limited as well. In the Concanavalin A model, the extract displayed
      weak effects. CONCLUSIONS: Taking into account underlying mechanisms in both
      hepatitis models, we demonstrate the extract's radical scavenging capacity.
      Neoboutonia velutina displays a potent hepatoprotective effect mediated through
      radical scavenging properties.

PMID- 29357847
TI  - Critically appraised topic on adverse food reactions of companion animals (5):
      discrepancies between ingredients and labeling in commercial pet foods.
AB  - BACKGROUND: Elimination dietary trials for the diagnosis of adverse food
      reactions (food allergies) in dogs and cats are often conducted with commercial
      pet foods while relying on their label to select those not containing previously
      eaten ingredients. There are concerns that industrial pet foods might contain
      unlisted food sources that could negate the usefulness of performing food trials.
      Furthermore, unidentified ingredients might cause clinical reactions in patients
      hypersensitive to such items. RESULTS: We searched two article databases on July
      7, 2017 and January 12, 2018 for relevant articles, and we screened abstracts
      from the leading international veterinary dermatology congresses for suitable
      material. Additional citations were found in the selected papers. In all, we
      extracted data from 17 articles and one abstract. The studies varied both in the
      number of pet foods tested (median: 15; range: 1 to 210) and that of ingredients
      specifically evaluated (median: 4; range: 1 to 11). Studies most often employed
      either PCR to detect DNA or ELISA to identify proteins from one or more vegetal
      or animal species; two studies used mass spectrometry to increase the number of
      detectable proteins. The various methods found ingredients that were not on the
      label in 0 to 83% (median: 45%) of tested diets; this percentage varied between
      33 and 83% in pet foods with "novel/limited" ingredients proposed for elimination
      diets. Similarly, ingredients were found to be missing from the label in 0 to 38%
      (median: 1%) of tested foods. Finally, six studies evaluated, among others,
      several hydrolysate-containing pet foods: mislabeling with unlabeled or missing
      ingredients was found only in one diet. CONCLUSIONS: The mislabeling of pet foods
      appears rather common, even in those with "novel" or "limited" ingredients
      proposed for elimination diets. Unexpected added ingredients are more frequently
      detected than those missing from the label. There is insufficient information to
      determine if the presence of a contaminating component will lead to a clinical
      reaction in a patient allergic to it, as challenges with the mislabeled foods
      were not performed in dogs or cats allergic to such ingredients. The testing of
      hydrolysate-containing pet foods found only one instance of possible mislabeling.

PMID- 29357849
TI  - Indian adolescents' perceptions of the home food environment.
AB  - BACKGROUND: The home food environment has the potential to influence the eating
      behaviour of adolescents. This investigation aimed to understand Indian
      adolescents' perspectives of their home food environments. METHODS: Adolescents
      aged 14-16 years (n = 1026, 65.3% girls) attending private secondary schools in
      Kolkata completed a paper-based questionnaire during school time which included
      questions about family food rules, availability and accessibility of foods at
      home, and domestic cooking responsibility. Boys' and girls' opinions and
      experiences were compared through cross-tabulation analyses. RESULTS: Almost all
      the adolescents reported that fruits (91.6%) and vegetables (95.7%) were always
      available in their homes. Approximately two-fifths reported that sugar-sweetened
      beverages (36.2%) and salty snack foods (38.0%) were readily available. In 56.1%
      households, adolescents were expected to follow certain food rules during
      mealtimes (e.g. not talking with my mouth full). The majority of the respondents
      (80.4%) identified mothers as the primary meal providers, only a minority
      reported that fathers (5.1%) were responsible for preparation of family meals.
      CONCLUSION: This understanding of the family-environmental determinants of
      adolescent dietary habits provides useful directions for nutrition promotion
      interventions. Health and educational professionals associated with adolescents
      could communicate about the development of healthy home food environments to
      provide positive health benefits for adolescents and their families.

PMID- 29357848
TI  - Identification, synthesis and regulatory function of the N-acylated homoserine
      lactone signals produced by Pseudomonas chlororaphis HT66.
AB  - BACKGROUND: Pseudomonas chlororaphis HT66 isolated from the rice rhizosphere is
      an important plant growth-promoting rhizobacteria that produce phenazine-1
      carboxamide (PCN) in high yield. Phenazine production is regulated by a quorum
      sensing (QS) system that involves the N-acylated homoserine lactones (AHLs)-a
      prevalent type of QS molecule. RESULTS: Three QS signals were detected by thin
      layer chromatography (TLC) and high-performance liquid chromatography-mass
      spectrometry (HPLC-MS/MS), which identified to be N-(3-hydroxy hexanoyl)-L
      homoserine lactone (3-OH-C6-HSL), N-(3-hydroxy octanoyl)-L-homoserine lactone (3
      OH-C8-HSL) and N-(3-hydroxy decanoyl)-L-homoserine lactone (3-OH-C10-HSL). The
      signal types and methods of synthesis were different from that in other phenazine
      producing Pseudomonas strains. By non-scar deletion and heterologous expression
      techniques, the biosynthesis of the AHL-signals was confirmed to be only
      catalyzed by PhzI, while other AHLs synthases i.e., CsaI and HdtS were not
      involved in strain HT66. In comparison to wild-type HT66, PCN production was 2.3
      folds improved by over-expression of phzI, however, phzI or phzR mutant did not
      produce PCN. The cell growth of HT66?phzI mutant was significantly decreased, and
      the biofilm formation in phzI or phzR inactivated strains of HT66 decreased to
      various extents. CONCLUSION: In conclusion, the results demonstrate that PhzI
      PhzR system plays a critical role in numerous biological processes including
      phenazine production.

PMID- 29357850
TI  - Occurrence and molecular epidemiology of Giardia duodenalis infection in dog
      populations in eastern Spain.
AB  - BACKGROUND: Giardia duodenalis is one of the most common enteric parasites in
      domestic animals including dogs. Young animals are more prone to the infection,
      with clinical manifestations ranging from asymptomatic to acute or chronic
      diarrhoea. Dogs are primarily infected by canine-specific (C-D) assemblages of G.
      duodenalis. However, zoonotic assemblages A and B have been increasingly
      documented in canine isolates, raising the question of whether and to which
      extent dogs can act as natural reservoirs of human giardiosis. METHODS: In this
      cross-sectional epidemiological survey we assessed the molecular diversity of G.
      duodenalis in dogs in the province of Castellon, Eastern Spain. A total of 348
      individual faecal samples from sheltered (n = 218), breeding (n = 24), hunting (n
      = 68), shepherd (n = 24), and pet (n = 14) dogs were collected between 2014 and
      2016. Detection of G. duodenalis cysts in faecal material was carried out by
      direct fluorescence microscopy as a screening test, whereas a qPCR targeting the
      small subunit ribosomal RNA gene of the parasite was subsequently used as a
      confirmatory method. RESULTS: Giardia duodenalis was detected in 36.5% (95% CI:
      31.6-41.7%) of dogs. No significant differences in prevalence rates could be
      demonstrated among dogs according to their sex and geographical origin, but
      breeding (45.8%; 95% CI: 27.9-64.9%) and sheltered (40.4%; 95% CI: 34.1-47.0%)
      dogs harboured significantly higher proportions of G. duodenalis. Multi-locus
      sequence-based genotyping of the glutamate dehydrogenase and beta-giardin genes
      of G. duodenalis allowed the characterization of 35 canine isolates that were
      unambiguously assigned to assemblages A (14.3%), B (22.9%), C (5.7%), and D
      (37.1%). A number of inter-assemblage mixed infections including A + B (11.4%), A
      + D (2.9%), and A + B + D (5.7%) were also identified. CONCLUSIONS: Data
      presented here are strongly indicative of high infection pressures in kennelled
      animals. Zoonotic sub-assemblages AII, BIII, and BIV were responsible for a
      considerable proportion of the G. duodenalis infections detected, but very few of
      the genotypes identified have been previously documented in Spanish human
      populations. Although possible, zoonotic transmission between dogs and humans
      seems an infrequent event in this Spanish region.

PMID- 29357851
TI  - Bioactivity of essential oils extracted from Cupressus macrocarpa branchlets and
      Corymbia citriodora leaves grown in Egypt.
AB  - BACKGROUND: Cupressus macrocarpa Hartw and Corymbia citriodora (Hook.) K.D. Hill
      & L.A.S. Johnson, widely grown in many subtropical areas, are used for commercial
      purposes, such as in perfumery, cosmetics, and room fresheners. Their potential
      as a source of antimicrobial compounds may be useful in different applications.
      METHODS: The chemical composition of essential oils (EOs) from C. macrocarpa
      branchlets and C. citriodora leaves was analyzed by using gas chromatography-mass
      spectrometry (GC/MS). Antibacterial and antifungal activities were assessed by
      the micro-dilution method to determine the minimum inhibitory concentrations
      (MICs), and minimum fungicidal concentrations (MFCs), and minimum bactericidal
      concentrations (MBCs). Further, the antioxidant capacity of the EOs was
      determined via 2,2'-diphenypicrylhydrazyl (DPPH) and beta-carotene-linoleic acid
      assays. RESULTS: Terpinen-4-ol (23.7%), alpha-phellandrene (19.2%), alpha
      citronellol (17.3%), and citronellal were the major constituents of EO from C.
      macrocarpa branchlets, and alpha-citronellal (56%), alpha-citronellol (14.7%),
      citronellol acetate (12.3%), isopulegol, and eucalyptol were the primary
      constituents of EO from C. citriodora leaves. Antibacterial activity with MIC
      values of EO from C. citriodora leaves was ranged from 0.06 mg/mL to 0.20 mg/mL,
      and MBC from 0.12 mg/mL against E. coli to 0.41 mg/mL. EO from C. macrocarpa
      branchlets showed less activity against bacterial strains. The MIC values against
      tested fungi of the EO from C. citriodora ranged from 0.11 to 0.52 mg/mL while
      for EO from C. macrocarpa from 0.29 to 3.21 mg/mL. The MIC and MFC values of EOs
      against P. funiculosum were lower than those obtained from Ketoconazole (KTZ)
      (0.20; 0.45; 0.29 and 0.53 mg/mL, respectively, vs 0.21 and 0.41 mg/mL.
      Antioxidant activity of the EO from C. citriodora was higher than that of the
      positive control but lower than that of the standard butylhydroxytoluene (BHT)
      (IC50 = 5.1 +/- 0.1 MUg/mL). CONCLUSION: The results indicate that the EO from
      Egyptian trees such as C. citriodora leaves may possesses strong bactericidal and
      fungicidal activities and can be used as an agrochemical for controlling plant
      pathogens and in human disease management which will add crop additive value.

PMID- 29357853
TI  - Does women's caste make a significant contribution to adolescent pregnancy in
      Nepal? A study of Dalit and non-Dalit adolescents and young adults in Rupandehi
      district.
AB  - BACKGROUND: Adolescent pregnancy is a public health concern worldwide. There are
      disparities in the occurrence of adolescence pregnancy in different social groups
      and settings; however, few studies have focused on the contribution of a woman's
      caste in early pregnancy in Nepal. This study aimed to examine the association
      between caste and adolescent pregnancy; and investigate factors that influence
      this among women of Dalit and non-Dalit caste groups. METHODS: A cross sectional
      survey among 457 women, age between 14 and 24 years was carried out in Rupandehi
      district of Nepal. Bivariate and multivariate logistic regression analysis using
      a stepwise entry method was performed to assess the association of women's caste,
      ethnicity and other socio-demographic and individual factors with early
      pregnancy. RESULTS: Over two thirds of the participants (69%) were pregnant
      during adolescence. The highest percentage of adolescent pregnancies were
      reported among women from Janajati groups (77%) and the lowest in Brahmin/Chhetri
      caste groups (45%); while 72.5% of women from Dalit caste groups reported
      adolescent pregnancy. When adjusted for demographic and individual variables,
      early pregnancy was less likely among women who were from Brahman/Chhetri (OR:
      0.60; 95% CI: 0.30, 1.22) and Madhesi/Muslim (OR 0.56; 95% CI: 0.23, 1.36)
      compared to women from the Dalit caste, but multivariate regression analysis
      found none of these were statistically significant. Women who had secondary level
      education (OR: 0.34; 95% CI: 0.17, 0.65), had married after 17 years of age (OR:
      0.02; 95% CI: 0.01, 0.14) and had attended fairs/clubs (OR: 0.40; CI: 0.21, 0.79)
      were significantly less likely to experience early age pregnancy. Women who drank
      alcohol (OR: 5.18; 95% CI: 1.02, 26.32) were significantly more likely to become
      pregnant during adolescence compared to women who did not drink alcohol.
      CONCLUSIONS: Women's caste had no direct contributory role in the early pregnancy
      of the sample. Education, age at marriage and individual behaviours were the key
      contributing factors. Reducing the number of adolescent pregnancies requires
      addressing the factors that lead to and perpetuate child marriage; keeping girls
      within education systems for longer; increase the knowledge and control of girls
      over their own reproductive health and planning; and actions that promote gender
      respect within relationships, decision-making and negotiation among both girls
      and boys.

PMID- 29357852
TI  - ADMP controls the size of Spemann's organizer through a network of self
      regulating expansion-restriction signals.
AB  - BACKGROUND: The bone morphogenetic protein (BMP) signaling gradient is central
      for dorsoventral patterning in amphibian embryos. This gradient is established
      through the interaction of several BMPs and BMP antagonists and modulators, some
      secreted by Spemann's organizer, a cluster of cells coordinating embryonic
      development. Anti-dorsalizing morphogenetic protein (ADMP), a BMP-like
      transforming growth factor beta ligand, negatively affects the formation of the
      organizer, although it is robustly expressed within the organizer itself.
      Previously, we proposed that this apparent discrepancy may be important for the
      ability of ADMP to scale the BMP gradient with embryo size, but how this is
      achieved is unclear. RESULTS: Here we report that ADMP acts in the establishment
      of the organizer via temporally and mechanistically distinct signals. At the
      onset of gastrulation, ADMP is required to establish normal organizer-specific
      gene expression domains, thus displaying a dorsal, organizer-promoting function.
      The organizer-restricting, BMP-like function of ADMP becomes apparent slightly
      later, from mid-gastrula. The organizer-promoting signal of ADMP is mediated by
      the activin A type I receptor, ACVR1 (also known as activin receptor-like kinase
      2, ALK2). ALK2 is expressed in the organizer and is required for organizer
      establishment. The anti-organizer function of ADMP is mediated by ACVRL1 (ALK1),
      a putative ADMP receptor expressed in the lateral regions flanking the organizer
      that blocks expansion of the organizer. Truncated ALK1 prevents the organizer
      restricting effects of ADMP overexpression, suggesting a ligand-receptor
      interaction. We also present a mathematical model of the regulatory network
      controlling the size of the organizer. CONCLUSIONS: We show that the opposed,
      organizer-promoting and organizer-restricting roles of ADMP are mediated by
      different receptors. A self-regulating network is proposed in which ADMP
      functions early through ALK2 to expand its own expression domain, the organizer,
      and later functions through ALK1 to restrict this domain. These effects are
      dependent on ADMP concentration, timing, and the spatial localization of the two
      receptors. This self-regulating temporal switch may control the size of the
      organizer and the genes expressed within in response to genetic and external
      stimuli during gastrulation.

PMID- 29357854
TI  - Individualised treatment targets in patients with type-2 diabetes and
      hypertension.
AB  - AIM: Patients with type-2 diabetes mellitus (T2DM) are at high risk of
      cardiovascular events, accentuated in the presence of hypertension. At present,
      it is unclear to what extent the guidelines for the management of T2DM,
      advocating reduction in HbA1c levels to below target levels, are being adhered to
      in clinical practice. METHODS: DIALOGUE was a prospective, observational, non
      interventional registry performed across multiple centres in Germany. Patients
      aged 18 years or older who had T2DM and hypertension for whom the treating
      physician considered blood glucose lowering medication as inadequate and/or not
      safe/tolerable and chose to add a further oral drug or switch drug treatment were
      included. Patients were assigned a treatment target HbA1c value (<= 6.5%
      [strict]; > 6.5 to <= 7.0% [intermediate]; > 7.0 to <= 7.5% [lenient]). RESULTS:
      8568 patients with T2DM and hypertension were enrolled. 6691 (78.1%) had 12-month
      follow-up. Patients who were assigned a strict HbA1c treatment target (n = 2644)
      were younger, had shorter diabetes duration, and less comorbidity in comparison
      to those with intermediate (n = 2912) or lenient targets (n = 1135). Only 53.1%
      of patients achieved their HbA1c treatment target (46.2% [strict], 56.8%
      [intermediate], 59.4% [lenient]). There was little sign of treatment
      intensification for patients that had not achieved their HbA1c target.
      CONCLUSIONS: Achievement of treatment targets was poor, leaving many patients
      with sub-optimal blood glucose levels. The apparent reluctance of physicians to
      intensify antidiabetic drug therapy is alarming, especially considering the
      evidence pointing to an association of hyperglycaemia and microvascular
      complications in patients with T2DM.

PMID- 29357855
TI  - A qualitative study of culturally embedded factors in complementary and
      alternative medicine use.
AB  - BACKGROUND: Within the intercultural milieu of medical pluralism, a nexus of
      worldviews espousing distinct explanatory models of illness, our research aims at
      exploring factors leading to complementary and alternative medicine (CAM) use
      with special attention to their cultural context. METHODS: The results are based
      on medical anthropological fieldwork (participant observation and in-depth
      interviews) spanning a period from January 2015 to May 2017 at four clinics of
      Traditional Chinese Medicine in Budapest, Hungary. Participant observation
      involved 105 patients (males N = 42); in-depth interviews were conducted with
      patients (N = 9) and practitioners (N = 9). The interviews were coded with
      Interpretative Phenomenological Analysis; all information was aggregated
      employing Atlas.ti software. RESULTS: In order to avoid the dichotomization of
      "push and pull factors," results obtained from the fieldwork and interviews were
      structured along milestones of the patient journey. These points of reference
      include orientation among sources of information, biomedical diagnosis, patient
      expectations and the physician-patient relationship, the biomedical treatment
      trajectory and reasons for non-adherence, philosophical congruence, and alternate
      routes of entry into the world of CAM. All discussed points which are a departure
      from the strictly western therapy, entail an underlying socio-cultural
      disposition and must be scrutinized in this context. CONCLUSIONS: The influence
      of one's culturally determined explanatory model is ubiquitous from the onset of
      the patient journey and exhibits a reciprocal relationship with subjective
      experience. Firsthand experience (or that of the Other) signifies the most
      reliable source of information in matters of illness and choice of therapy.
      Furthermore, the theme of (building and losing) trust is present throughout the
      patient journey, a determining factor in patient decision-making and dispositions
      toward both CAM and biomedicine.

PMID- 29357857
TI  - The genotoxicity of an aqueous extract of Gyejibokryeong-hwan.
AB  - BACKGROUND: Gyejibokryeong-hwan (Guizhi Fuling Wan in China), a mixture of five
      herbal plants, is a well-known treatment for renal diseases including those
      associated with climacteric syndrome. However, the genotoxicity of Gyejibokryeong
      hwan has not yet been well established. METHODS: The present study investigated
      that the genotoxicity of an aqueous extract of Gyejibokryeong-hwan (GJBRHE): an
      in vitro chromosomal aberration test using Chinese hamster lung cells, an in
      vitro bacterial reverse mutation assay (Ames test) with Salmonella typhimurium
      and Escherichia coli strains, and an in vivo micronucleus test using ICR mouse
      bone marrow. RESULTS: GJBRHE with or without the S9 mix showed no genotoxicity in
      the Ames test up to 5000 MUg/plate or in the in vivo MN test up to 2000 mg/kg
      body weight. In contrast, the chromosomal aberration test showed that GJBRHE
      induced an increase in the number of chromosomal aberrations compared with the
      control after treatment for 6 h with 4200 MUg/mL GJBRHE in the presence of the S9
      mix and for 22 h with 800 MUg/mL GJBRHE in the absence of the S9 mix.
      CONCLUSIONS: GJBRHE did not cause detectable genotoxic effects in the bacterial
      mutation test or the in vivo MN test, however genotoxic effect was detected in
      the in vitro chromosomal aberration assay. Our results suggest that GJBRHE may be
      associated with a low risk of carcinogenesis. Thus, further detailed experiments
      would be needed to clarify the compound responsible for inducing this
      genotoxicity of GJBRHE and to determine its mechanism.

PMID- 29357858
TI  - Seroprevalence and risk factors associated with Pseudorabies virus infection in
      Tibetan pigs in Tibet.
AB  - BACKGROUND: Pseudorabies (PR) is an important emerging infectious disease that is
      characterized by fever, extreme itching and encephalomyelitis. However, it is
      still unclear whether Tibetan pigs are exposed to Pseudorabies virus (PRV) or
      not. The present study was conducted to investigate the seroprevalence of PRV
      infection in Tibetan pigs in Nyingchi area of Tibet through enzyme-linked
      immunosorbent assay (ELISA). A total of 368 serum samples from Tibetan pigs were
      collected during 2015. RESULTS: Results showed that 58 (15.76%) samples were
      found positive for PRV antibodies with further distribution of 18.23%, 13.42% and
      6.25% from Nyingchi, Mainling and Gongbo'gyamda areas on the Tibetan plateau,
      respectively; along with 12.10%, 17.71% and 17.57% prevalence of PRV in
      juveniles, sub-adults and adults, respectively. The prevalence of PRV infection
      between male (14.61%) and female (16.84%) showed non-significant difference (P >
      0.05). The risk factors of infection were found to be associated with feed type,
      age and altitude. CONCLUSIONS: The present study depicts a serious concern with a
      new emerging infectious disease in Tibetan pigs in Tibet, China.

PMID- 29357856
TI  - Clinical relevance of contextual factors as triggers of placebo and nocebo
      effects in musculoskeletal pain.
AB  - Placebo and nocebo effects are embodied psycho-neurobiological responses capable
      of modulating pain and producing changes at different neurobiological, body at
      perceptual and cognitive levels. These modifications are triggered by different
      contextual factors (CFs) presented in the therapeutic encounter between patient
      and healthcare providers, such as healing rituals and signs. The CFs directly
      impact on the quality of the therapeutic outcome: a positive context, that is a
      context characterized by the presence of positive CFs, can reduce pain by
      producing placebo effects, while a negative context, characterized by the
      presence of negative CFs, can aggravate pain by creating nocebo effects. Despite
      the increasing interest about this topic; the detailed study of CFs as triggers
      of placebo and nocebo effects is still lacked in the management of
      musculoskeletal pain.Increasing evidence suggest a relevant role of CFs in
      musculoskeletal pain management. CFs are a complex sets of internal, external or
      relational elements encompassing: patient's expectation, history, baseline
      characteristics; clinician's behavior, belief, verbal suggestions and therapeutic
      touch; positive therapeutic encounter, patient-centered approach and social
      learning; overt therapy, posology of intervention, modality of treatment
      administration; marketing features of treatment and health care setting.
      Different explanatory models such as classical conditioning and expectancy can
      explain how CFs trigger placebo and nocebo effects. CFs act through specific
      neural networks and neurotransmitters that were described as mediators of placebo
      and nocebo effects.Available findings suggest a relevant clinical role and impact
      of CFs. They should be integrated in the clinical reasoning to increase the
      number of treatment solutions, boosts their efficacy and improve the quality of
      the decision-making. From a clinical perspective, the mindful manipulation of CFs
      represents a useful opportunity to enrich a well-established therapy in
      therapeutic setting within the ethical border. From a translational perspective,
      there is a strong need of research studies on CFs close to routine and real-world
      clinical practice in order to underline the uncertainty of therapy action and
      help clinicians to implement knowledge in daily practice.

PMID- 29357860
TI  - Solid type primary intraosseous squamous cell carcinoma in a cat.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) is the most common nonodontogenic oral
      tumor in cats. In the jaw, it usually presents as an ulceroproliferative lesion
      associated with enlargement of the affected bone. CASE PRESENTATION: This report
      describes the case of a cat in which clinical and radiographic findings of a
      mandibular swelling were suggestive of an aggressive process, but the oral mucosa
      was unaffected. The results of histopathological and immunohistochemical
      examination of the samples obtained from the intraosseous lesion were consistent
      with SCC. The animal was euthanized 5 months after initial presentation as a
      result of the severe progression of the disease, and no other primary tumors were
      identified at necropsy. CONCLUSIONS: Based on the clinicopathological,
      microscopic, and immunohistochemical staining features, as well as the absence of
      a primary tumor at a distant site, we propose that the term, solid type primary
      intraosseous SCC (PIOSCC), be used to describe this neoplasia, as it shares
      similar features with human PIOSCC.

PMID- 29357859
TI  - Clinical and genomic safety of treatment with Ginkgo biloba L. leaf extract (IDN
      5933/Ginkgoselect(r)Plus) in elderly: a randomised placebo-controlled clinical
      trial [GiBiEx].
AB  - BACKGROUND: Numerous health benefits have been attributed to the Ginkgo biloba
      leaf extract (GBLE), one of the most extensively used phytopharmaceutical drugs
      worldwide. Recently, concerns of the safety of the extract have been raised after
      a report from US National Toxicology Program (NTP) claimed high doses of GBLE
      increased liver and thyroid cancer incidence in mice and rats. A safety study has
      been designed to assess, in a population of elderly residents in nursing homes,
      clinical and genomic risks associated to GBLE treatment. METHODS: GiBiEx is a
      multicentre randomized clinical trial, placebo controlled, double blinded, which
      compared subjects randomized to twice-daily doses of either 120-mg of IDN 5933
      (also known as Ginkgoselect(r)Plus) or to placebo for a 6-months period. IDN 5933
      is extracted from dried leaves and contains 24.3% flavone glycosides and 6.1% of
      terpene lactones (2.9% bilobalide, 1.38% ginkgolide A, 0.66% ginkgolide B, 1.12%
      ginkgolide C) as determined by HPLC. The study was completed by 47 subjects, 20
      in the placebo group and 27 in the treatment group. Clinical (adverse clinical
      effect and liver injury) and genomic (micronucleus frequency, comet assay, c-myc,
      p53, and ctnnb1 expression profile in lymphocytes) endpoints were assessed at the
      start and at the end of the study. RESULTS: No adverse clinical effects or
      increase of liver injury markers were reported in the treatment group. The
      frequency of micronuclei [Mean Ratio (MR) = 1.01, 95% Confidence Intervals (95%
      CI) 0.86-1.18), and DNA breaks (comet assay) (MR = 0.91; 95% CI 0.58-1.43), did
      not differ in the two study groups. No significant difference was found in the
      expression profile of the three genes investigated. CONCLUSIONS: None of the
      markers investigated revealed a higher risk in the treatment group, supporting
      the safety of IDN 5933 at doses prescribed and for duration of six months. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT03004508 , December 20, 2016.
      Trial retrospectively registered.

PMID- 29357861
TI  - Radiological changes do not influence clinical mid-term outcome in stemless
      humeral head replacements with hollow screw fixation: a prospective radiological
      and clinical evaluation.
AB  - BACKGROUND: Stemless shoulder arthroplasty is a fairly new concept. Clinical and
      radiological follow-up is essential to prove implant safety and concept. This
      prospective single-centre study was performed to evaluate the influence of
      radiological changes on clinical mid-term outcome following stemless humeral head
      replacement with hollow screw fixation. METHODS: Short- and mid-term radiological
      and clinical evaluations were performed in 73 consecutive shoulders treated
      mainly for idiopathic and posttraumatic osteoarthritis with stemless humeral head
      arthroplasty including 40 hemi- (HSA) and 33 total shoulder arthroplasties (TSA).
      Operating times of stemless implantations were compared to 110 stemmed anatomical
      shoulder prostheses. Appearances of humeral radiolucencies or radiological signs
      of osteolysis or stress shielding were assessed on standardized radiographs.
      Patients' clinical outcome was evaluated using the Constant score and patients'
      satisfaction was documented. RESULTS: Radiological changes, detected in 37.0%,
      did not affect clinical outcome. Constant scores significantly improved from
      baseline to short and mid-term follow-up (p < 0.001). The majority of patients
      (96.2%) were satisfied with the procedure. No loosening of the humeral head
      component was detected during a mean follow-up of 58 months. Operating times were
      significantly shorter with stemless compared to stemmed implants (p < 0.001).
      CONCLUSIONS: Clinical mid-term outcome after stemless humeral head replacement
      was not affected by radiological changes. TRIAL REGISTRATION: The institutional
      review board (St. Vincent Hospital Vienna; 201212_EK01; date of issue:
      11.12.2012) approved the study. The trial was registered at ClinicalTrials.gov (
      NCT02754024 ). Retrospective registration.

PMID- 29357862
TI  - The mortality risk factor of community acquired pneumonia patients with chronic
      obstructive pulmonary disease: a retrospective cohort study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of the most
      common comorbidities in community acquired pneumonia (CAP) patients. We aimed to
      investigate the characteristics and mortality risk factors of COPD patients
      hospitalized with CAP. METHODS: A retrospective cohort study was conducted at
      Shanghai Pulmonary Hospital and Shanghai Dahua Hospital. Clinical and demographic
      data in patients diagnosed with CAP were collected between January 2015 and June
      2016. Logistic regression analysis was performed to screen mortality risk factors
      of COPD patients hospitalized with CAP. RESULTS: Of the total 520 CAP patients,
      230 (44.2%) patients had been diagnosed comorbid with COPD (COPD-CAP). CAP
      patients comorbid with COPD patients had higher rate of need for ICU admission
      (18.3% vs 13.1%) and need for NIMV (26.1% vs 1.4%) than without COPD (nCOPD-CAP).
      The PSI, CURB-65 and APACHE-II scores in COPD-CAP patients were higher than that
      in nCOPD-CAP patients (95 vs 79, P < 0.001; 1 vs 1, P < 0.001; 13 vs 8, P <
      0.001, respectively). Logistic regression analysis indicated that aspiration, D
      dimer > 2.0 MUg/mL and CURB-65 >= 3 were risk factors associated with in-hospital
      mortality ((odd ratio) OR = 5.678, OR = 4.268, OR = 20.764, respectively) in COPD
      CAP patients. The risk factors associated with 60-day mortality in COPD-CAP
      patients were comorbid with coronary heart disease, aspiration, need for NIMV
      (non-invasive mechanical ventilation) and CURB-65 >= 3 (OR = 5.206, OR = 7.921,
      OR = 3.974, OR = 18.002, respectively). CONCLUSIONS: COPD patients hospitalized
      with CAP had higher rate of need for NIMV, need for ICU admission and severity
      scores than those without COPD. Aspiration, D-dimer > 2.0 MUg/mL, comorbid with
      coronary heart disease, need for NIMV and CURB-65 >= 3 were mortality risk
      factors in CAP patients comorbid with COPD.

PMID- 29357864
TI  - Clinicians can independently predict 30-day hospital readmissions as well as the
      LACE index.
AB  - BACKGROUND: Significant effort has been directed at developing prediction tools
      to identify patients at high risk of unplanned hospital readmission, but it is
      unclear what these tools add to clinicians' judgment. In our study, we assess
      clinicians' abilities to independently predict 30-day hospital readmissions, and
      we compare their abilities with a common prediction tool, the LACE index.
      METHODS: Over a period of 50 days, we asked attendings, residents, and nurses to
      predict the likelihood of 30-day hospital readmission on a scale of 0-100% for
      359 patients discharged from a General Medicine Service. For readmitted versus
      non-readmitted patients, we compared the mean and standard deviation of the
      clinician predictions and the LACE index. We compared receiver operating
      characteristic (ROC) curves for clinician predictions and for the LACE index.
      RESULTS: For readmitted versus non-readmitted patients, attendings predicted a
      risk of 48.1% versus 31.1% (p < 0.001), residents predicted 45.5% versus 34.6% (p
      0.002), and nurses predicted 40.2% versus 30.6% (p 0.011), respectively. The LACE
      index for readmitted patients was 11.3, versus 10.1 for non-readmitted patients
      (p 0.003). The area under the curve (AUC) derived from the ROC curves was 0.689
      for attendings, 0.641 for residents, 0.628 for nurses, and 0.620 for the LACE
      index. Logistic regression analysis suggested that the LACE index only added
      predictive value to resident predictions, but not attending or nurse predictions
      (p < 0.05). CONCLUSIONS: Attendings, residents, and nurses were able to
      independently predict readmissions as well as the LACE index. Improvements in
      prediction tools are still needed to effectively predict hospital readmissions.

PMID- 29357865
TI  - #Deathbedlive: the end-of-life trajectory, reflected in a cancer patient's
      tweets.
AB  - BACKGROUND: Understanding physical and psycho-social illness trajectories towards
      the end of life can help in the planning of palliative and supportive care. With
      terminal patients increasingly seeking and sharing health information and support
      via social media, it is timely to examine whether these trajectories are
      reflected in their digital narratives. In this exploratory study, we analysed the
      Twitter feed of prominent cancer sufferer and physician, Kate Granger, over the
      final 6 months of her life. METHODS: With the consent of Kate's widower, Chris
      Pointon, 1628 Twitter posts from @GrangerKate were manually screened. The 550
      tweets judged relevant to her disease were qualitatively content analysed with
      reference to the six modifiable dimensions of the patient experience in Emanuel
      and Emanuel's 'framework for a good death'. The frequency of each tweet category
      was charted over time and textual content was examined and cross-referenced with
      key events, to obtain a deeper understanding of its nature and significance.
      RESULTS: Tweets were associated with physical symptoms (N = 270), psychological
      and cognitive symptoms (N = 213), social relationships and support (N = 85),
      economic demands and care giving needs (N = 85), hopes and expectations (N = 51)
      and spiritual beliefs (N = 7). While medical treatments and procedures were
      discussed in detail, medical information-seeking was largely absent, likely
      reflecting Kate clinical expertise. Spirituality was expressed more as hope in
      treatments or "someone out there listening", than in religious terms. The high
      value of Kate's palliative care team was a dominant theme in the support
      category, alongside the support she received from her online community of fellow
      sufferers, friends, family and colleagues. Significant events, such as medical
      procedures and hospital stays generated the densest Twitter engagement.
      Transitions between trajectory phases were marked by changes in the relative
      frequency of tweet-types. CONCLUSIONS: In Kate's words, "the power of patient
      narrative cannot be underestimated". While this analysis spanned only 6 months,
      it yielded rich insights. The results reflect theorised end-of-life dimensions
      and reveal the potential of social media data and digital bio-ethnography to
      shine a light on terminal patients' lived experiences, coping strategies and
      support needs, suggesting new opportunities for enhancing personalised palliative
      care and avenues for further research.

PMID- 29357863
TI  - Accumulation mode particles and LPS exposure induce TLR-4 dependent and
      independent inflammatory responses in the lung.
AB  - BACKGROUND: Accumulation mode particles (AMP) are formed from engine combustion
      and make up the inhalable vapour cloud of ambient particulate matter pollution.
      Their small size facilitates dispersal and subsequent exposure far from their
      original source, as well as the ability to penetrate alveolar spaces and
      capillary walls of the lung when inhaled. A significant immuno-stimulatory
      component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria
      breakdown. As LPS is implicated in the onset and exacerbation of asthma, the
      presence or absence of LPS in ambient particulate matter (PM) may explain the
      onset of asthmatic exacerbations to PM exposure. This study aimed to delineate
      the effects of LPS and AMP on airway inflammation, and potential contribution to
      airways disease by measuring airway inflammatory responses induced via activation
      of the LPS cellular receptor, Toll-like receptor 4 (TLR-4). METHODS: The effects
      of nebulized AMP, LPS and AMP administered with LPS on lung function, cellular
      inflammatory infiltrate and cytokine responses were compared between wildtype
      mice and mice not expressing TLR-4. RESULTS: The presence of LPS administered
      with AMP appeared to drive elevated airway resistance and sensitivity via TLR-4.
      Augmented TLR4 driven eosinophilia and greater TNF-alpha responses observed in
      AMP-LPS treated mice independent of TLR-4 expression, suggests activation of
      allergic responses by TLR4 and non-TLR4 pathways larger than those induced by LPS
      administered alone. Treatment with AMP induced macrophage recruitment independent
      of TLR-4 expression. CONCLUSIONS: These findings suggest AMP-LPS as a stronger
      stimulus for allergic inflammation in the airways then LPS alone.

PMID- 29357866
TI  - Family caregiver mistreatment of the elderly: prevalence of risk and associated
      factors.
AB  - BACKGROUND: The detection of elder mistreatment is emerging as a public health
      priority; however, abusive behaviors exercised by caregivers are little known and
      rarely detected among primary health care professionals. This study aims to
      estimate the prevalence of risk of abuse against community-residing elderly with
      moderate to severe dependency whose caregivers are relatives. In addition, we aim
      to describe the association between such a risk and socio-demographic variables,
      cognitive and dependency state of the victim, and the scale of the caregiver's
      anxiety, depression, and burden. METHODS: Cross-sectional study developed in 72
      Primary Health Care teams from Barcelona, Spain. Participants were caregivers and
      their dependent care recipients (N = 829). Home interviews included the Caregiver
      Abuse Screen (CASE); self-reported abuse from care recipient; activities of daily
      living and cognitive state of the care recipient; anxiety and depression in
      caregivers and Caregiver Burden Scale. The relationship prior to the dependency,
      positive aspects of caregiving, and social support for the caregiver were also
      assessed. Multivariate analysis was performed using logistic regression with risk
      of abuse as dependent variable. RESULTS: Caregivers were mainly women (82.8%)
      with a mean age of 63.3 years. Caregivers and care recipients lived in the same
      household in 87.4% of cases, and 86.6% had enjoyed a good previous relationship.
      Care recipients were women (65.6%), with a mean age of 84.2 years, and 64.2% had
      moderate to severe cognitive impairment. CASE demonstrated a prevalence of 33.4%
      (95% CI: 30.3-36.7) of abuse risk by the caregiver. Logistic regression showed as
      statistically significant: caregiver burden (OR = 2.75; 95% CI: 1.74-4.33),
      caregiver anxiety (OR = 2.06; 95% CI: 1.40-3.02), caregiver perception of
      aggressive behavior in the care recipient (OR = 7.24; 95% CI: 4.99-10.51), and a
      bad previous relationship (OR = 4.66; 95% CI: 1.25-17.4). CONCLUSIONS: Prevalence
      of risk of abuse is high among family caregivers. Our study has found risk
      factors in family caregivers that are preventable to an extent, namely: anxiety
      and feelings of burden. It is essential to become aware of these risk factors and
      their causes to intervene and help primary as well secondary prevention.

PMID- 29357868
TI  - Manual therapy in the treatment of patients with hemophilia B and inhibitor.
AB  - BACKGROUND: The main clinical manifestations of hemophilia are muscle and joint
      bleeding. Recurrent bleeding leads to a degenerative process known as hemophilic
      arthropathy. The development of inhibitors (antibodies against FVIII/FIX
      concentrates) is the main complication in the treatment of hemophilia. The
      objective was to assess the safety and efficacy of manual therapy treatment in a
      patient with hemophilia and inhibitor. CASE PRESENTATION: A 26-year-old patient
      with hemophilia B and inhibitor received physiotherapy treatment based on manual
      therapy for 3 months, with a frequency of 2 sessions per week. The joint status
      was evaluated using the Hemophilia Joint Health Score; pain was assessed with the
      Visual Analog Scale; and the range of movement was evaluated using a universal
      goniometer. The patient developed no joint bleeding in the knees or ankles as a
      result of the physiotherapy treatment. Following treatment, improvements were
      noted in the range of movement of knees and ankles, the perception of pain in
      both knees, and ankle functionality. CONCLUSIONS: Until now, manual therapy using
      joint traction was contraindicated in patients with hemophilia and inhibitor, as
      it was feared to cause possible joint bleeding. This is the first case study to
      address the safety and efficacy of manual therapy in a patient with hemophilia
      and an inhibitor. The results of this study may help to establish which manual
      therapy treatments are indicated in patients with hemophilic arthropathy and
      inhibitors. Thus, a physiotherapy program based on manual therapy may be safe in
      patients with hemophilia and inhibitor and such therapy may improve joint
      condition, pain, and joint range of motion in patients with hemophilia and
      inhibitor. Randomized clinical trials are needed to confirm the results of this
      case study.

PMID- 29357867
TI  - Generic health literacy measurement instruments for children and adolescents: a
      systematic review of the literature.
AB  - BACKGROUND: Health literacy is an important health promotion concern and recently
      children and adolescents have been the focus of increased academic attention. To
      assess the health literacy of this population, researchers have been focussing on
      developing instruments to measure their health literacy. Compared to the wider
      availability of instruments for adults, only a few tools are known for younger
      age groups. The objective of this study is to systematically review the field of
      generic child and adolescent health literacy measurement instruments that are
      currently available. METHOD: A systematic literature search was undertaken in
      five databases (PubMed, CINAHL, PsycNET, ERIC, and FIS) on articles published
      between January 1990 and July 2015, addressing children and adolescents <=18
      years old. Eligible articles were analysed, data was extracted, and synthesised
      according to review objectives. RESULTS: Fifteen generic health literacy
      measurement instruments for children and adolescents were identified. All, except
      two, are self-administered instruments. Seven are objective measures (performance
      based tests), seven are subjective measures (self-reporting), and one uses a
      mixed-method measurement. Most instruments applied a broad and multidimensional
      understanding of health literacy. The instruments were developed in eight
      different countries, with most tools originating in the United States (n = 6).
      Among the instruments, 31 different components related to health literacy were
      identified. Accordingly, the studies exhibit a variety of implicit or explicit
      conceptual and operational definitions, and most instruments have been used in
      schools and other educational contexts. While the youngest age group studied was
      7-year-old children within a parent-child study, there is only one instrument
      specifically designed for primary school children and none for early years.
      CONCLUSIONS: Despite the reported paucity of health literacy research involving
      children and adolescents, an unexpected number of health literacy measurement
      studies in children's populations was found. Most instruments tend to measure
      their own specific understanding of health literacy and not all provide
      sufficient conceptual information. To advance health literacy instruments, a much
      more standardised approach is necessary including improved reporting on the
      development and validation processes. Further research is required to improve
      health literacy instruments for children and adolescents and to provide knowledge
      to inform effective interventions.

PMID- 29357869
TI  - Low use of artemisinin-based combination therapy for febrile children under five
      and barriers to correct fever management in Benin: a decade after WHO
      recommendation.
AB  - BACKGROUND: Artemisinin-based combination therapy (ACT), used to treat
      uncomplicated malaria cases, is one of the main strategies of malaria control and
      elimination. One of the main objectives of the Benin National Malaria Control
      Program's (NMCP) strategic plan is to ensure that at least 80% of uncomplicated
      malaria is treated with ACT within 24 h. Therefore, it was of great interest to
      measure whether the country case management of fever amongst children under five,
      adhered to the NMCP's strategic plan and look into the barriers to the use of
      ACT. METHODS: A cross-sectional survey based on a cluster and multi-stage
      sampling was conducted in two rural health districts in Benin. We recruited 768
      and 594 children under five years were included in the northern and in the
      southern respectively. Data was collected on the general use of ACT and on the
      correct use of ACT that adheres to the NMCP's strategy, as well as the barriers
      that prevent the proper management of fever amongst children. To assess the
      certain predictors of ACT usage, logistic regression was used, while taking into
      account the cluster random effect. RESULTS: Among febrile children aged 6 to 59
      months, 20.7% in the south and 33.9% in north received ACT. The correct use of
      ACT, was very low, 5.8% and in southern and 8.6% northern areas. Caregivers who
      received information on ACT were 3.13 time more likely in the south and 2.98 time
      more likely in the north to give ACT to their feverish child, PPR = 3.13[1.72
      4.15] and PPR = 2.98 [2.72-3.11] respectively. Chloroquine and quinine, other
      malaria treatments not recommended by NMCP, were still being used in both areas:
      12.3 and 3.3% in the south and 11.4 and 3.0% in the north. CONCLUSION: In Benin,
      the use and the correct use of ACT for febrile children remains low. The study
      also showed that having received information about the use of ACT is positively
      associated with the use of ACT. This point highlights the fact that efforts may
      not have been sufficiently integrated with social communication, which should be
      based on the behavioural determinants of populations.

PMID- 29357870
TI  - Primaquine ineligibility in anti-relapse therapy of Plasmodium vivax malaria: the
      problem of G6PD deficiency and cytochrome P-450 2D6 polymorphisms.
AB  - The hypnozoite reservoir of Plasmodium vivax represents both the greatest
      obstacle and opportunity for ultimately eradicating this species. It is silent
      and cannot be diagnosed until it awakens and provokes a clinical attack with
      attendant morbidity, risk of mortality, and opportunities for onward
      transmission. The only licensed drug that kills hypnozoites is primaquine, which
      attacks the hypnozoite reservoir but imposes serious obstacles in doing so-at
      hypnozoitocidal doses, it invariably causes a threatening acute haemolytic
      anaemia in patients having an inborn deficiency in glucose-6-phosphate
      dehydrogenase (G6PD), affecting about 8% of people living in malaria endemic
      nations. That problem excludes a large number of people from safe and effective
      treatment of the latent stage of vivax malaria: the G6PD deficient, pregnant or
      lactating women, and young infants. These groups were estimated to comprise 14.3%
      of populations resident in the 95 countries with endemic vivax malaria. Another
      important obstacle regarding primaquine in the business of killing hypnozoites is
      its apparent metabolism to an active metabolite exclusively via cytochrome P-450
      isozyme 2D6 (CYP2D6). Natural polymorphisms of this allele create genotypes
      expressing impaired enzymes that occur in over 20% of people living in Southeast
      Asia, where more than half of P. vivax infections occur globally. Taken together,
      the estimated frequencies of these primaquine ineligibles due to G6PD toxicity or
      impaired CYP2D6 activity composed over 35% of the populations at risk of vivax
      malaria. Much more detailed work is needed to refine these estimates, derive
      probabilities of error for them, and improve their ethnographic granularity in
      order to inform control and elimination strategy and tactics.

PMID- 29357871
TI  - Factors related with public open space use among adolescents: a study using GPS
      and accelerometers.
AB  - BACKGROUND: Low physical activity levels and high levels of sedentary time among
      adolescents call for population wide interventions. Public open spaces can be
      important locations for adolescents' physical activity. This study aimed to
      describe the prevalence, frequency and context of public open space visitation
      and to gain insight into the individual, social and physical environmental
      factors associated with public open space use among 12- to 16-year-old Flemish
      (Belgian) adolescents. METHODS: Global positioning system devices, accelerometers
      and one-on-one interviews were used to measure location-specific activity levels,
      time spent at, reasons for using and accompaniment at public open spaces among
      173 adolescents. Multilevel hurdle and gamma models were used to estimate the
      associations between the independent variables (age, gender, ethnicity,
      education, sport club membership and accompaniment) and the amount of time,
      sedentary time, light-, moderate- to vigorous- and vigorous-intensity physical
      activity at public open spaces. RESULTS: Three out of four participants had
      visited a public open space (for recreational purposes) and participants were
      most often accompanied by friends/classmates. Mainly public transportation
      stops/stations were used, and subsequently the most reported reason for public
      open space use was "to wait for something or someone". Furthermore, boys, younger
      adolescents, non-western-European adolescents and lower educated adolescents were
      more likely to use public open spaces. Additionally, boys and younger adolescents
      were more likely to accumulate physical activity at public open spaces. The only
      social environmental variable associated with time spent at public open spaces
      was accompaniment by siblings: adolescents spent more time at public open spaces
      when accompanied by their siblings. CONCLUSIONS: Public open spaces may be
      effective areas to promote physical activity among groups at risk for physical
      inactivity (i.e. low educated and non-western-European adolescents).
      Additionally, girls and older adolescents were less likely to visit and be
      physically active at public open spaces. Therefore, urban planners should
      consider adding attractive features, in order to encourage physical activity
      among girls and older adolescents at public open spaces. Furthermore, creating
      public open spaces that are attractive for youth of all ages could contribute to
      adolescents visiting public open spaces accompanied by siblings.

PMID- 29357873
TI  - The importance of morphological identification of African anopheline mosquitoes
      (Diptera: Culicidae) for malaria control programmes.
AB  - BACKGROUND: The correct identification of disease vectors is the first step
      towards implementing an effective control programme. Traditionally, for malaria
      control, this was based on the morphological differences observed in the adults
      and larvae between different mosquito species. However, the discovery of species
      complexes meant that genetic tools were needed to separate the sibling species
      and today there are standard molecular techniques that are used to identify the
      two major malaria vector groups of mosquitoes. On the assumption that species
      diagnostic DNA polymerase chain reaction (PCR) assays are highly species
      specific, experiments were conducted to investigate what would happen if non
      vector species were randomly included in the molecular assays. METHODS:
      Morphological keys for the Afrotropical Anophelinae were used to provide the a
      priori identifications. All mosquito specimens were then subjected to the
      standard PCR assays for members of the Anopheles gambiae complex and Anopheles
      funestus group. RESULTS: One hundred and fifty mosquitoes belonging to 11
      morphological species were processed. Three species (Anopheles pretoriensis,
      Anopheles rufipes and Anopheles rhodesiensis) amplified members of the An.
      funestus group and four species (An. pretoriensis, An. rufipes, Anopheles listeri
      and Anopheles squamosus) amplified members of the An. gambiae complex.
      CONCLUSIONS: Morphological identification of mosquitoes prior to PCR assays not
      only saves time and money in the laboratory, but also ensures that data received
      by malaria vector control programmes are useful for targeting the major vectors.

PMID- 29357872
TI  - Ribosome profiling of the retrovirus murine leukemia virus.
AB  - BACKGROUND: The retrovirus murine leukemia virus (MuLV) has an 8.3 kb RNA genome
      with a simple 5'-gag-pol-env-3' architecture. Translation of the pol gene is
      dependent upon readthrough of the gag UAG stop codon; whereas the env gene is
      translated from spliced mRNA transcripts. Here, we report the first high
      resolution analysis of retrovirus gene expression through tandem ribosome
      profiling (RiboSeq) and RNA sequencing (RNASeq) of MuLV-infected cells. RESULTS:
      Ribosome profiling of MuLV-infected cells was performed, using the translational
      inhibitors harringtonine and cycloheximide to distinguish initiating and
      elongating ribosomes, respectively. Meta-analyses of host cell gene expression
      demonstrated that the RiboSeq datasets specifically captured the footprints of
      translating ribosomes at high resolution. Direct measurement of ribosomal
      occupancy of the MuLV genomic RNA indicated that ~ 7% of ribosomes undergo gag
      stop codon readthrough to access the pol gene. Initiation of translation was
      found to occur at several additional sites within the 5' leaders of the gag and
      env transcripts, upstream of their respective annotated start codons.
      CONCLUSIONS: These experiments reveal the existence of a number of previously
      uncharacterised, ribosomally occupied open reading frames within the MuLV genome,
      with possible regulatory consequences. In addition, we provide the first direct
      measurements of stop codon readthrough efficiency during cellular infection.

PMID- 29357874
TI  - Quality of life after low-dose rate-brachytherapy for prostate carcinoma - long
      term results and literature review on QLQ-C30 and QLQ-PR25 results in published
      brachytherapy series.
AB  - BACKGROUND: Patient-reported health-related quality of life (HRQOL) differs
      between treatment options for prostate carcinoma. Long-term HRQOL data in
      brachytherapy series are scarce. Therefore, we analyzed prostate-specific and
      general HRQOL in patients treated with brachytherapy for prostate carcinoma after
      long-term follow-up. METHODS: Two hundred ninety-six patients with prostate
      carcinoma were treated with brachytherapy (01/1998-11/2003). General and prostate
      specific HRQOL were measured using EORTC-QLQ-C30 and EORTC-QLQ-PR25,
      respectively. Patients were asked to complete the questionnaires after a median
      follow-up of 141 (119-181) months. QLQ-C30 results were compared to the German
      reference population. QLQ-PR25 results were compared to an earlier follow-up
      after a median of 51 months (no published QLQ-PR25 reference population for
      comparison). Additionally, a literature review on HRQOL data in brachytherapy
      series was performed. RESULTS: One hundred six (35.8%) patients were lost to
      follow-up, 70 (23.6%) had died. 120 (40.5%) patients were contacted. 80
      questionnaires were returned (27% of the original cohort; 91% of alive patients
      were >=70 years). Sexual activity declined over time (mean scores: 40.5 vs. 45.5;
      p = 0.006), hormonal treatment-related symptoms, problems associated with
      incontinence aids, and burden of obstructive urinary symptoms did not differ
      significantly compared to the 51-month follow-up. General HRQOL was numerically
      better in our cohort as compared to the German reference population (> 16%
      relative difference for both age strata; < 70 and >=70 years). CONCLUSIONS: Our
      results indicate that symptom-burden after long-term follow-up and associated
      prostate-specific HRQOL remains relatively stable from 51 to 141 months. General
      HRQOL in surviving patients was numerically better compared to the reference
      population.

PMID- 29357875
TI  - Optimization of dose distributions of target volumes and organs at risk during
      stereotactic body radiation therapy for pancreatic cancer with dose-limiting auto
      shells.
AB  - BACKGROUND: To identify optimization of dose distributions of target volumes and
      decrease of radiation doses to normal tissues during stereotactic body radiation
      therapy (SBRT) for pancreatic cancer with dose-limiting auto-shells. METHODS:
      With the same prescription dose, dose constraints of normal organs and
      calculation algorithm, treatment plans of each eligible patient were re-generated
      with 3 shells, 5 shells and 7 shells, respectively. The prescription isodose line
      and beam number of each patient in 3-shell, 5-shell and 7-shell plan remained the
      same. Hence, a triplet data set of dosimetric parameters was generated and
      analyzed. RESULTS: As the increase of shell number, the conformal index, volumes
      encompassed by 100% prescription isodose line and 30% prescription isodose line
      significantly decreased. The new conformal index was higher in 3-shell group than
      that in 5-shell and 7-shell group. A sharper dose fall-off was found in 5-shell
      and 7-shell group compared to 3-shell group. And the tumor coverage in 7-shell
      was better than that of 3-shell and 5-shell. Lower D5cc of the intestine, D10cc
      of the stomach, Dmax of the spinal cord and smaller V10 of the spleen was
      confirmed in 7-shell group compared to 3-shell group. CONCLUSIONS: More conformal
      dose distributions of target volumes and lower radiation doses to normal organs
      could be performed with the increase of dose-limiting auto-shells, which may be
      more beneficial to potential critical organs without established dose
      constraints.

PMID- 29357876
TI  - Training scholars in dissemination and implementation research for cancer
      prevention and control: a mentored approach.
AB  - BACKGROUND: As the field of D&I (dissemination and implementation) science grows
      to meet the need for more effective and timely applications of research findings
      in routine practice, the demand for formalized training programs has increased
      concurrently. The Mentored Training for Dissemination and Implementation Research
      in Cancer (MT-DIRC) Program aims to build capacity in the cancer control D&I
      research workforce, especially among early career researchers. This paper
      outlines the various components of the program and reports results of systematic
      evaluations to ascertain its effectiveness. METHODS: Essential features of the
      program include selection of early career fellows or more experienced
      investigators with a focus relevant to cancer control transitioning to a D&I
      research focus, a 5-day intensive training institute, ongoing peer and senior
      mentoring, mentored planning and work on a D&I research proposal or project,
      limited pilot funding, and training and ongoing improvement activities for
      mentors. The core faculty and staff members of the MT-DIRC program gathered
      baseline and ongoing evaluation data regarding D&I skill acquisition and
      mentoring competency through participant surveys and analyzed it by iterative
      collective reflection. RESULTS: A majority (79%) of fellows are female, assistant
      professors (55%); 59% are in allied health disciplines, and 48% focus on cancer
      prevention research. Forty-three D&I research competencies were assessed; all
      improved from baseline to 6 and 18 months. These effects were apparent across
      beginner, intermediate, and advanced initial D&I competency levels and across the
      competency domains. Mentoring competency was rated very highly by the fellows-
      higher than rated by the mentors themselves. The importance of different
      mentoring activities, as rated by the fellows, was generally congruent with their
      satisfaction with the activities, with the exception of relatively greater
      satisfaction with the degree of emotional support and relatively lower
      satisfaction for skill building and opportunity initially. CONCLUSIONS: These
      first years of MT-DIRC demonstrated the program's ability to attract, engage, and
      improve fellows' competencies and skills and implement a multicomponent mentoring
      program that was well received. This account of the program can serve as a basis
      for potential replication and evolution of this model in training future D&I
      science researchers.

PMID- 29357877
TI  - Salvage thoracic surgery in patients with lung cancer: potential indications and
      benefits.
AB  - BACKGROUND: To investigate the feasibility and efficacy of salvage lung resection
      and describe the possible indications and contraindications in patients with
      primary lung cancer. METHODS: Thirty patients undergoing anatomical salvage lung
      resection were classified into three groups: GI, patients with progressive lung
      tumor despite definitive chemo- and/or radiotherapy; GII, patients who underwent
      emergency resection; and GIII, patients in whom neoadjuvant or definitive chemo-
      and/or radiotherapy was contraindicated because of severe comorbidities. The
      groups were compared based on, peri- and postoperative factors, and survival
      rates. RESULTS: The morbidity rate was 70%. Revision surgery was required in 23%
      of patients. Morbidity was affected by lower hematocrit and hemoglobin levels (P
      = 0.05). Mean hospital stay was 11 +/- 4 days, which was longer in patients in
      whom complications developed (P = 0.0003). The in-hospital or 30-day mortality
      rate was 3%. Mean relapse-free survival and overall survivals were 14 +/- 12 and
      19 +/- 13 months. CONCLUSION: Patients with progression of the persistent primary
      tumor after definitive chemo- and/or radiotherapy can undergo salvage lung
      resection with acceptable mortality and high morbidity rates, if the tumor is
      considered resectable. Other indications may be considered for salvage lung
      resection based on each patient's specific evaluation.

PMID- 29357878
TI  - Unconjugated bilirubin induces pyroptosis in cultured rat cortical astrocytes.
AB  - BACKGROUND: Bilirubin-induced neurological dysfunction (BIND), a severe
      complication of extreme neonatal hyperbilirubinemia, could develop into permanent
      neurodevelopmental impairments. Several studies have demonstrated that
      inflammation and nerve cell death play important roles in bilirubin-induced
      neurotoxicity; however, the underlying mechanism remains unidentified. METHODS:
      The present study was intended to investigate whether pyroptosis, a highly
      inflammatory form of programmed cell death, participated in the bilirubin
      mediated toxicity on cultured rat cortical astrocytes. Further, VX-765, a potent
      and selective competitive drug, was used to inhibit the activation of caspase-1.
      The effects of VX-765 on astrocytes treated with bilirubin, including the cell
      viability, morphological changes of the cell membrane and nucleus, and the
      production of pro-inflammation cytokines, were observed. RESULTS: Stimulation of
      the astrocytes with unconjugated bilirubin (UCB) at the conditions mimicking
      those of jaundiced newborns significantly increased the activation of caspase-1.
      Further, caspase-1 activation was inhibited by treatment with VX-765. Compared
      with UCB-treated astrocytes, the relative cell viability of VX-765-pretreated
      astrocytes was improved; meanwhile, the formation of plasma membrane pores was
      prevented, as measured by lactate dehydrogenase release, trypan blue staining,
      and ethidium bromide (EtBr) uptake. Moreover, DNA fragmentation was partly
      attenuated and the release of IL-1beta and IL-18 was apparently decreased.
      CONCLUSION: Pyroptosis is involved in the process of UCB-induced rat cortical
      astrocytes' injury in vitro and may be the missing link of cell death and
      inflammatory response exacerbating UCB-related neurotoxicity. More importantly,
      the depression of caspase-1 activation, the core link of pyroptosis, attenuated
      UCB-induced cellular dysfunction and cytokine release, which might shed light on
      a new therapeutic approach to BIND.

PMID- 29357879
TI  - Specific microRNA signatures responsible for immune disturbance related to hip
      fracture in aged rats.
AB  - BACKGROUND: Hip fracture is commonly associated with an overwhelming inflammatory
      response, which may lead to high rates of morbidity and mortality in the elderly.
      MicroRNAs (miRNAs) play important roles in the functions of immune system.
      However, the association between miRNA dysregulation and immune disturbance (IMD)
      related to elderly hip fracture is largely unknown. METHODS: In this study,
      microarray profiling was carried out to evaluate the differential expression
      patterns of miRNAs in plasma of the aged hip fracture rats with IMD, those
      without IMD, and normal aged rats, followed by validation using quantitative real
      time reverse transcription polymerase chain reaction (qRT-PCR). Genes and
      signaling pathways of the dysregulated miRNAs related to elderly hip fracture
      induced IMD were investigated in silico using Gene Ontology and analysis of Kyoto
      Encyclopedia of Genes or Genomes. RESULTS: Dead or moribund rats with hip
      fracture exhibited significantly reduced TNF-alpha/IL-10 ratio compared with
      healthy controls and other hip fracture rats, which were therefore named as hip
      fracture rats with IMD. Seven serum miRNAs in hip fracture rats with IMD were
      significantly downregulated. qRT-PCR and in silico analysis revealed that miR
      130a-3p likely participated in regulating the hip fracture-induced IMD.
      Furthermore, Western blot experiment demonstrated that in lung tissue, the
      reduction of miR-130a-3p was accompanied with the increase of the protein
      expression of interferon regulatory factor-1 (IRF1) and sphingosine-1-phosphate
      receptor 1 (SIPR1). CONCLUSIONS: miR-130a-3p desregulation may be associated with
      elderly hip fracture-induced IMD, which might act as a new potential biomarker
      for the diagnosis and prognosis of elderly hip fracture-induced IMD and a
      potential therapeutic target as well.

PMID- 29357880
TI  - The role of the complement system in traumatic brain injury: a review.
AB  - Traumatic brain injury (TBI) is an important cause of disability and mortality in
      the western world. While the initial injury sustained results in damage, it is
      the subsequent secondary cascade that is thought to be the significant
      determinant of subsequent outcomes. The changes associated with the secondary
      injury do not become irreversible until some time after the start of the cascade.
      This may present a window of opportunity for therapeutic interventions aiming to
      improve outcomes subsequent to TBI. A prominent contributor to the secondary
      injury is a multifaceted inflammatory reaction. The complement system plays a
      notable role in this inflammatory reaction; however, it has often been overlooked
      in the context of TBI secondary injury. The complement system has homeostatic
      functions in the uninjured central nervous system (CNS), playing a part in
      neurodevelopment as well as having protective functions in the fully developed
      CNS, including protection from infection and inflammation. In the context of CNS
      injury, it can have a number of deleterious effects, evidence for which primarily
      comes not only from animal models but also, to a lesser extent, from human post
      mortem studies. In stark contrast to this, complement may also promote
      neurogenesis and plasticity subsequent to CNS injury. This review aims to explore
      the role of the complement system in TBI secondary injury, by examining evidence
      from both clinical and animal studies. We examine whether specific complement
      activation pathways play more prominent roles in TBI than others. We also explore
      the potential role of complement in post-TBI neuroprotection and CNS
      repair/regeneration. Finally, we highlight the therapeutic potential of targeting
      the complement system in the context of TBI and point out certain areas on which
      future research is needed.

PMID- 29357881
TI  - Physical exercise, gut, gut microbiota, and atherosclerotic cardiovascular
      diseases.
AB  - Arteriosclerotic cardiovascular diseases (ASCVDs) are the leading cause of
      morbidity and mortality worldwide and its risk can be independently decreased by
      regular physical activity. Recently, ASCVD and its risk factors were found to be
      impacted by the gut microbiota through its diversity, distribution and
      metabolites. Meanwhile, several experiments demonstrated the relationship between
      physical exercise and diversity, distribution, metabolite of the gut microbiota
      as well as its functions on the lipid metabolism and chronic systematic
      inflammation. In this review, we summarize the current knowledge on the effects
      of physical exercise on ASCVD through modulation of the gut microbiota and
      intestinal function.

PMID- 29357882
TI  - Quantitative investigation of the direct interaction between Hemagglutinin and
      fusion proteins of Peste des petits ruminant virus using surface Plasmon
      resonance.
AB  - BACKGROUND: The specific and dynamic interaction between the hemagglutinin (H)
      and fusion (F) proteins of morbilliviruses is a prerequisite for the
      conformational rearrangements and membrane fusion during infection process. The
      two heptad repeat regions (HRA and HRB) of F protein are both important for the
      triggering of F protein. METHODS: In this study, the direct interactions of Peste
      des petits ruminants virus (PPRV) H with F, HRA and HRB were quantitatively
      evaluated using biosensor surface plasmon resonance (SPR). RESULTS: The binding
      affinities of immobilized pCMV-HA-H (HA-H) interacted with proteins pCMV-HA-F (HA
      F) and pCMV-HA-HRB (HA-HRB) (KD = 1.91 * 10- 8 M and 2.60 * 10- 7 M,
      respectively) reacted an order of magnitude more strongly than that of pCMV-HA
      HRA (HA-HRA) and pCMV-HA-Tp IGFR-LD (HA) (KD = 1.08 * 10- 4 M and 1.43 * 10- 4 M,
      respectively). CONCLUSIONS: The differences of the binding affinities suggested
      that HRB is involved in functionally important intermolecular interaction in the
      fusion process.

PMID- 29357883
TI  - Comparison of the clinical efficacy between single-agent and dual-agent
      concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous
      cell carcinoma: a multicenter retrospective analysis.
AB  - BACKGROUND: Some Chinese patients with esophageal squamous cell carcinomaare
      often treated with single-agent concurrent chemoradiotherapy. However, no results
      have been reported from randomized controlled clinical trials comparing single
      agent with double-agent concurrent chemoradiotherapy. It therefore remains
      unclear whether these regimens are equally clinically effective. In this study,
      we retrospectively analyzed and compared the therapeutic effects of single-agent
      and double-agent concurrent chemoradiotherapy in patients with unresectable
      esophageal squamous cell carcinoma. METHODS: This study enrolled 168 patients who
      received definitive concurrent chemoradiotherapy for locally advanced
      unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015.
      We evaluated survival time and toxicity. The Kaplan-Meier method was used to
      estimate survival data. The log-rank test was used in univariate analysis A Cox
      proportional hazards regression model was used to conduct a multivariate analysis
      of the effects of prognostic factors on survival. RESULTS: In this study, 100
      (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination
      chemoradiotherapy, respectively. The estimate 5-year progression-free survival
      (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than
      that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively),
      but there were no significant differences (P = 0.367 and 0.161, respectively).
      Multivariate analysis showed that sex, age,and radiotherapy dose had no
      significant effects on OS or PFS. Only disease stage was associated with OS and
      PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual
      agent group, the incidence of acute toxicity and the incidence of 3 and4 grade
      toxicity were higher than single-agent group. CONCLUSION: The 5-year PFS and OS
      rates of dual-agent therapy were higher than those of single-agent concurrent
      chemoradiotherapy for patients with unresectable esophageal squamous cell
      carcinoma; however, there were no significant differences in univariate analysis
      and multivariable analysis. Single-agent concurrent chemotherapy had less
      toxicity than a double-drug regimen. Therefore, we suggest that single therapis
      not inferior to dual therapy y. In the future, we aim to confirm our hypothesis
      through a prospective randomized study.

PMID- 29357884
TI  - From denial to awareness: a conceptual model for obtaining equity in healthcare.
AB  - BACKGROUND: Although Swedish legislation prescribes equity in healthcare, studies
      have reported inequalities, both in face-to-face encounters and in telephone
      nursing. Research has suggested that telephone nursing has the capability to
      increase equity in healthcare, as it is open to all and not limited by long
      distances. However, this requires an increased awareness of equity in healthcare
      among telephone nurses. The aim of this study was to explore and describe
      perceptions of equity in healthcare among Swedish telephone nurses who had
      participated in an educational intervention on equity in health, including which
      of the power constructs gender, ethnicity and age they commented upon most
      frequently. Further, the aim was to develop a conceptual model for obtaining
      equity in healthcare, based on the results of the empirical investigation.
      METHOD: A qualitative method was used. Free text comments from questionnaires
      filled out by 133 telephone nurses before and after an educational intervention
      on equity in health, as well as individual interviews with five participants,
      were analyzed qualitatively. The number of comments related to inequity based on
      gender, ethnicity or age in the free text comments was counted descriptively.
      RESULTS: Gender was the factor commented upon the least and ethnicity the most.
      Four concepts were found through the qualitative analysis: Denial, Defense,
      Openness, and Awareness. Some informants denied inequity in healthcare in
      general, and in telephone nursing in particular. Others acknowledged it, but
      argued that they had workplace routines that protected against it. There were
      also examples of an openness to the fact that inequity existed and a willingness
      to learn and prevent it, as well as an already high awareness of inequity in
      healthcare. CONCLUSION: A conceptual model was developed in which the four
      concepts were divided into two qualitatively different blocks, with Denial and
      Defense on one side of a continuum and Openness and Awareness on the other. In
      order to reach equity in healthcare, action is also needed, and that concept was
      therefore added to the model. The result can be used as a starting point when
      developing educational interventions for healthcare personnel.

PMID- 29357885
TI  - Hepatitis B infection and preeclampsia among pregnant Sudanese women.
AB  - BACKGROUND: Previous published studies have reported conflicting results of
      association between hepatitis B virus (HBV) infection and preeclampsia. There was
      no published data on HBV and preeclampsia in Africa including Sudan. The aim of
      the present study was to investigate the association between HBsAg seropositivity
      and preeclampsia. METHODS: A case -controls study (200 women in each arm) was
      conducted at Saad Abualila Maternity Hospital, Khartoum, Sudan. The cases were
      women with preeclampsia and the controls were healthy pregnant women. Socio
      demographic characteristics were gathered using questionnaire and HBsAg was
      investigated using an ELISA. RESULTS: There was no significant difference between
      the cases and the controls in their age, parity, residence, education and blood
      groups. The majority of the cases were mild preeclampsia (159; 79.5%). In
      comparison with the controls, a significantly higher number of the cases were
      HBsAg seropositive [30 (15.0%) vs.12 (6.0%), P = 0.005]. In binary regression
      women with HBsAg seropositive were at higher risk of preeclampsia than women who
      were HBsAg seronegative (OR = 2.86, 95%, CI = 1.41-5.79, P = 0.003). CONCLUSION:
      In the current study HBsAg seropositivity is associated with preeclampsia.
      Preventive measure should be implemented.

PMID- 29357886
TI  - Modelling the immunosuppressive effect of liver SBRT by simulating the dose to
      circulating lymphocytes: an in-silico planning study.
AB  - BACKGROUND: Tumor immune-evasion and associated failure of immunotherapy can
      potentially be overcome by radiotherapy, which however also has detrimental
      effects on tumor-infiltrating and circulating lymphocytes (CL). We therefore
      established a model to simulate the radiation-dose delivered to CL. METHODS: A
      MATLAB-model was established to quantify the CL-dose during SBRT of liver
      metastases by considering the factors: hepatic blood-flow, -velocity and
      transition-time of individual hepatic segments, as well as probability-based
      recirculation. The effects of intra-hepatic tumor-location and size,
      fractionation and treatment planning parameters (VMAT, 3DCRT, photon-energy, dose
      rate and beam-on-time) were analyzed. A threshold dose >=0.5Gy was considered
      inactivating CL and CL0.5 (%) is the proportion of inactivated CL. RESULTS: Mean
      liver dose was mostly influenced by treatment-modality, whereas CL0.5 was mostly
      influenced by beam-on-time. 3DCRT and VMAT (10MV-FFF) resulted in lowest CL0.5
      values of 16 and 19%. Metastasis location influenced CL0.5, with a mean of 19%
      for both apical and basal and 31% for the central location. PTV-volume
      significantly increased CL0.5 from 27 to 67% (10MV-FFF) and from 31 to 98% (6MV
      FFF) for PTV-volumes ranging from 14cm3 to 268cm3. CONCLUSION: A simulation-model
      was established, quantifying the strong effects of treatment-technique, tumor
      location and tumor-volume on dose to CL with potential implications for immune
      optimized treatment-planning in the future.

PMID- 29357887
TI  - Practice and consensus-based strategies in diagnosing and managing systemic
      juvenile idiopathic arthritis in Germany.
AB  - BACKGROUND: Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory
      disease associated with chronic arthritis. Early diagnosis and effective therapy
      of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative
      of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus
      based strategies to harmonize diagnostic and therapeutic approaches in Germany.
      METHODS: We analyzed data on patients diagnosed with SJIA from 3 national
      registries in Germany. Subsequently, via online surveys and teleconferences among
      pediatric rheumatologists with a special expertise in the treatment of SJIA, we
      identified current diagnostic and treatment approaches in Germany. Those were
      harmonized via the formulation of statements and, supported by findings from a
      literature search. Finally, an in-person consensus conference using nominal group
      technique was held to further modify and consent the statements. RESULTS: Up to
      50% of patients diagnosed with SJIA in Germany do not fulfill the International
      League of Associations for Rheumatology (ILAR) classification criteria, mostly
      due to the absence of chronic arthritis. Our findings suggest that chronic
      arthritis is not obligatory for the diagnosis and treatment of SJIA, allowing a
      diagnosis of probable SJIA. Malignant, infectious and hereditary autoinflammatory
      diseases should be considered before rendering a diagnosis of probable SJIA.
      There is substantial variability in the initial treatment of SJIA. Based on
      registry data, most patients initially receive systemic glucocorticoids, however,
      increasingly substituted or accompanied by biological agents, i.e. interleukin
      (IL)-1 and IL-6 blockade (up to 27.2% of patients). We identified preferred
      initial therapies for probable and definitive SJIA, including step-up patterns
      and treatment targets for the short-term (resolution of fever, decrease in C
      reactive protein by 50% within 7 days), the mid-term (improvement in physician
      global and active joint count by at least 50% or a JADAS-10 score of maximally
      5.4 within 4 weeks) and the long-term (glucocorticoid-free clinically inactive
      disease within 6 to 12 months), and an explicit treat-to-target strategy.
      CONCLUSIONS: We developed consensus-based strategies regarding the diagnosis and
      treatment of probable or definitive SJIA in Germany.

PMID- 29357888
TI  - Realization of fully automated quantification of left ventricular volumes and
      systolic function using transthoracic 3D echocardiography.
AB  - BACKGROUND: Study on automated three-dimensional (3D) quantification of left
      heart parameters by using Heartmodel software is still in the early stage and
      fully automatic analysis was not clearly achieved. The aim of our study was to
      evaluate the performance of this new technology in measuring left ventricular
      (LV) volume and ejection fraction (EF) in patients with a variety of heart
      diseases on the basis of rationally determining the default endocardial border
      values. METHODS: Subjects with a variety of heart diseases were included
      prospectively. High quality Heartmodel images were selected to determine the end
      diastolic and end-systolic default values of endocardial border. The accuracy and
      reproducibility of automated three-dimensional echocardiography (3DE) for
      measuring LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF were
      evaluated with the traditional manual 3DE as the relative standard. RESULTS:
      Ninety seven subjects were enrolled in the study. The default endocardial border
      values were determined as 66% and 40% for end-diastole (ED) and end-systole (ES),
      respectively. Most of the subjects (84/97) were automatically analyzed by
      Heartmodel software without manual adjustment, revealing a close correlation of
      automated 3DE with manual 3DE in measuring EDV, ESV and EF (r-values: EDV: 0.96,
      ESV: 0.97, EF: 0.96). The EDV and ESV values obtained by automated 3DE were
      higher than those measured by manual 3DE (biases: EDV: 16 +/- 18 ml, ESV: 11 +/-
      12 ml). The intra- and inter-observer reproducibility of automated 3DE was better
      than that of manual 3DE. Automated 3DE with manual adjustment showed good
      consistency with manual 3DE in assessing the impairment degree of systolic
      function in patients with wall motion abnormalities (n = 58), (Kappa = 0.74, P =
      0.00). CONCLUSION: Fully automated 3DE quantification of LV volume and EF could
      be achieved in most patients. Since automated 3DE was accurate and more
      reproducible, it could replace the existing manual 3DE technology and be
      routinely used in clinical practice.

PMID- 29357889
TI  - A fuzzy set qualitative comparative analysis of 131 countries: which
      configuration of the structural conditions can explain health better?
AB  - BACKGROUND: According to the recommendations of the World Health Organization
      Commission On Social Determinants of Health (CSDH) for intersectoral action on
      health, the well-being of and equity in health within a population are achieved
      via a complex fusion of policies and actions. In this study, following the CSDH's
      approach and considering set-theoretic relations, we aimed to unravel this
      complexity and answer the kinds of questions that are outside the scope of
      conventional variable-oriented approach. METHODS: A fuzzy-set qualitative
      comparative analysis of 131 countries was conducted to examine the
      configurational effects of five macro-level structural conditions on life
      expectancy at birth. The potential causal conditions were level of country
      wealth, income inequality, quality of governance, education, and health system.
      The data collected from different international data sources were recorded during
      2004-2015. RESULTS: The intermediate solution of the truth table analysis
      indicated a configuration of conditions including high level of governance,
      education, wealth, and affluent health system to be consistently sufficient for
      high life expectancy. On the other hand, four configurations, each containing two
      or three conditions, were consistent with being usually sufficient to cause low
      life expectancy. CONCLUSIONS: We were able to configurationally explore the cases
      and specify the combinations of potentially causal conditions which were usually
      sufficient to explain high or low life expectancy in different countries. As a
      result, particular cases were identified for further research. In addition,
      research may provide support for the CSDH's recommendations emphasizing the
      importance of intersectoral action for health.

PMID- 29357890
TI  - Detection of asymptomatic carriers of malaria in Kohat district of Pakistan.
AB  - BACKGROUND: Kohat district is one of the medium intensity malaria transmission
      areas in Pakistan where asymptomatic carriers are likely to form a reservoir of
      infection. This study was done to explore the possibility of using microscopy,
      rapid diagnostic testing (RDT), real time polymerase chain reaction (RT-PCR) and
      RT-PCR followed by endpoint fluorometry (EPF) for detection of malaria in
      asymptomatic immediate family members of patients of malaria (homestead) and in a
      sample from the general population of Kohat. METHODS: This cross-sectional study
      was done at Combined Military Hospital Kohat and Molecular Lab of Riphah
      International University, Islamabad from Jan to Dec 2015. A total of 1000
      individuals including 200 microscopy positive patients of malaria, 400
      asymptomatic immediate family members (homestead) of the active patients of
      malaria and 400 apparently healthy controls were tested by microscopy, RDT and RT
      PCR. At the end of RT-PCR the result were read by EPF. RESULTS: In the 200
      malaria microscopy positive patients, 190 (95%) were RDT positive and all were RT
      PCR positive. In the 400 individuals from the homestead of malaria patients, 6
      (1.5%) individuals were malaria microscopy positive while RDT failed to pick any
      positive and 32 (8%) were RT-PCR positive for malaria. EPF of all the RT-PCR
      positive results were positive and the negative results were negative. The
      difference in the frequency of malaria in the homestead versus general population
      was very significant (p = 0.0002) and the relative risk of malaria was 4.0 times
      higher (95% CI 1.87-8.57). CONCLUSION: The chances of detecting asymptomatic
      malaria carriers is significantly higher in the homestead of malaria patients
      than in the general population and for this purpose RT-PCR with EPF can be very
      useful in the diagnosis of malaria especially with low parasite density.

PMID- 29357891
TI  - Comparison of the effects of exercise with chondroitin sulfate on knee
      osteoarthritis in rabbits.
AB  - BACKGROUND: The aim of the study is to compare the effects of exercise therapy
      with chondroitin sulfate (CS) therapy in an experimental model of osteoarthritis
      (OA). METHODS: Twenty-one New Zealand rabbits were randomly divided into four
      groups: normal group (N group, n = 3); OA control group (C group, n = 6); OA plus
      medication group (CS group, n = 6); and OA plus exercise group (E group, n = 6).
      Four weeks after modeling, the rabbits were subjected to exercise (artificial, 30
      min/time, 4 times/week) or medicated with CS (2% CS, 0.3 ml/time, once/week) for
      4 weeks. Histopathological changes in treated joints were examined after
      staining. X-ray and scanning electron microscopy was used to evaluate the
      different therapies by examining the surfaces and joint spaces of the articular
      cartilage. RT-qPCR was used to assess chondrogenic gene expression including
      Col2, Col10, mmp-13, il-1beta, adamats-5, and acan in the experimental groups.
      RESULTS: Histology showed both treatment groups resulted in cartilage that was in
      good condition, with increased numbers of chondrocytes, and the results of X-ray
      and scanning electron microscopy showed the therapeutic effect of exercise
      therapy is equivalent to CS therapy, surface articular cartilage was flat, and
      the of cartilage layer was thinning. All treated groups induced the expression of
      Col10 and Col2 and decreased expression of mmp-13, il-1beta, and adamats-5
      compared with the control groups. The expression of acan was upregulated in the E
      group and downregulated in the CS group. Furthermore, expression of Col10 was
      higher and il-1beta was lower in the exercise group compared to that of the CS
      group. CONCLUSION: These results indicate that exercise has a positive effect on
      OA compare with CS, and it also supplies reference for the movement mode to
      improve function.

PMID- 29357892
TI  - Semitransparent bandages based on chitosan and extracellular matrix for
      photochemical tissue bonding.
AB  - BACKGROUND: Extracellular matrices (ECMs) are often used in reconstructive
      surgery to enhance tissue regeneration and remodeling. Sutures and staples are
      currently used to fix ECMs to tissue although they can be invasive devices. Other
      sutureless and less invasive techniques, such as photochemical tissue bonding,
      cannot be coupled to ECMs because of their intrinsic opacity to light. RESULTS:
      We succeeded in fabricating a biocompatible and adhesive device that is based on
      ovine forestomach matrix (OFM) and a chitosan adhesive. The natural opacity of
      the OFM has been overcome by adding the adhesive into the matrix that allows for
      the light to effectively penetrate through it. The OFM-chitosan device is
      semitransparent (attenuation length ~ 106 um) and can be photoactivated by green
      light to bond to tissue. This device does not require sutures or staples and
      guarantees a bonding strength of ~ 23 kPa. CONCLUSIONS: A new semitransparent and
      biocompatible bandage has been successfully fabricated and characterized for
      sutureless tissue bonding.

PMID- 29357893
TI  - Alzheimer's disease diagnosis based on the Hippocampal Unified Multi-Atlas
      Network (HUMAN) algorithm.
AB  - BACKGROUND: Hippocampal atrophy is a supportive feature for the diagnosis of
      probable Alzheimer's disease (AD). However, even for an expert neuroradiologist,
      tracing the hippocampus and measuring its volume is a time consuming and
      extremely challenging task. Accordingly, the development of reliable fully
      automated segmentation algorithms is of paramount importance. MATERIALS AND
      METHODS: The present study evaluates (i) the precision and the robustness of the
      novel Hippocampal Unified Multi-Atlas Network (HUMAN) segmentation algorithm and
      (ii) its clinical reliability for AD diagnosis. For these purposes, we used a
      mixed cohort of 456 subjects and their T1 weighted magnetic resonance imaging
      (MRI) brain scans. The cohort included 145 controls (CTRL), 217 mild cognitive
      impairment (MCI) subjects and 94 AD patients from Alzheimer's Disease
      Neuroimaging Initiative (ADNI). For each subject the baseline, repeat, 12 and 24
      month follow-up scans were available. RESULTS: HUMAN provides hippocampal volumes
      with a 3% precision; volume measurements effectively reveal AD, with an area
      under the curve (AUC) AUC1 = 0.08 +/- 0.02. Segmented volumes can also reveal the
      subtler effects present in MCI subjects, AUC2 = 0.76 +/- 0.05. The algorithm is
      stable and reproducible over time, even for 24 month follow-up scans.
      CONCLUSIONS: The experimental results demonstrate HUMAN is a precise segmentation
      algorithm, besides hippocampal volumes, provided by HUMAN, can effectively
      support the diagnosis of Alzheimer's disease and become a useful tool for other
      neuroimaging applications.

PMID- 29357894
TI  - Embedding weight management into safety-net pediatric primary care: randomized
      controlled trial.
AB  - BACKGROUND: Implementing evidence-based recommendations for treating pediatric
      overweight and obesity is challenging in low-resource settings. We conducted a
      randomized controlled trial to evaluate the effects of implementing the American
      Academy of Pediatrics overweight/obesity recommendations using a Standard Care
      approach alone or with the addition of an enhanced program in a safety-net
      pediatric primary care setting (located in Bronx, New York, United States).
      METHODS: In a 12-month trial, families of children (age 7-12 years; body mass
      index >=85th American percentile for age and sex; 74% self-identified as
      Hispanic/Latino; n = 360) were randomly assigned to receive Standard Care Alone
      or Standard Care + Enhanced Program. An English/Spanish bilingual staff provided
      the Standard Care Alone consisting of quarterly semi-structured pediatrician
      visits targeting family-based behavioral changes. The Standard Care + Enhanced
      Program was enriched with eight Skill-Building Core and monthly Post-Core Support
      sessions. RESULTS: The mean body mass index Z-score declined in both arms (P <
      0.01) with no significant difference between the Standard Care Alone (0.12 kg
      [SE: 0.03]) and Standard Care + Enhanced Program (0.15 kg [SE: 0.03]) arm (P =
      0.15). Compared to the Standard Care Alone, the Standard Care + Enhanced Program
      resulted in significantly greater improvements in total cholesterol (P = 0.05),
      low-density lipoprotein cholesterol (P = 0.04), aspartate aminotransferase (P =
      0.02), and alanine transaminase (P = 0.03) concentrations. CONCLUSIONS: Safety
      net primary care settings can provide efficacious pediatric weight management
      services. Targeted family-based behavioral counseling helps overweight/obese
      children achieve a modest body mass index Z-score improvement. A more intensive
      lifestyle intervention program may improve some metabolic parameters. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT00851201 . Registered 23 February
      2009.

PMID- 29357895
TI  - Clinical significance of peripheral circulating tumor cell counts in colorectal
      polyps and non-metastatic colorectal cancer.
AB  - BACKGROUND: The presence of peripheral circulating tumor cells indicates the
      possible existence of a tumor in vivo; however, low numbers of circulating tumor
      cells (CTCs) can be detected in peripheral blood of healthy individuals as well
      as patients with benign tumors. It is not known whether peripheral CTC counts
      differ between patients with benign colorectal disease and those with colorectal
      cancer. METHODS: Comparative analysis of preoperative peripheral circulating
      tumor cells counts was completed in patients with benign colorectal disease
      (colorectal polyps) and non-metastatic cancer of the colon and rectum. RESULTS:
      The results of this analysis showed that patients with colorectal cancer had
      higher CTC counts than patients with colorectal polyps (3.47 +/- 0.32/3.2 ml vs
      1.49 +/- 0.2/3.2 ml, P < 0.001). Colorectal cancer patients with tumors of the
      sigmoid colon displayed the highest CTC counts (4.87 +/- 0.95/3.2 ml), followed
      by those with tumors of the rectum (3.73 +/- 0.54/3.2 ml), ascending colon (3.5
      +/- 0.63/3.2 ml), transverse colon (2.4 +/- 0.68/3.2 ml), and descending colon
      (2.08 +/- 0.46/3.2 ml). Colorectal polyp patients with polyps in the rectum
      showed the highest CTC counts (2.2 +/- 0.77/3.2 ml), followed by those with
      polyps in the ascending colon (1.82 +/- 0.54/3.2 ml), sigmoid colon (1.38 +/-
      0.25/3.2 ml), transverse colon (0.75 +/- 0.25/3.2 ml), and descending colon (0.33
      +/- 0.21/3.2 ml). The differences in CTC counts suggest that anatomical location
      of colorectal tumors may affect blood vessel metastasis. Meanwhile, patients with
      moderately differentiated and poorly differentiated tumors displayed higher
      peripheral blood CTC counts compared to those with well-differentiated tumors (P
      < 0.001). This result suggests that the type of tissue differentiation of
      colorectal tumors may act as another factor that affects blood vessel metastasis.
      CONCLUSIONS: Circulating tumor cells can be detected in the peripheral blood of
      colorectal cancer patients as well as patients with colorectal polyps. The
      differences in CTC counts suggest that anatomical location and the type of tissue
      differentiation of colorectal tumors may affect blood vessel metastasis.

PMID- 29357896
TI  - Feasibility of anthropometric indices to identify dyslipidemia among adults in
      Jilin Province: a cross-sectional study.
AB  - BACKGROUND: Dyslipidemia and other cardiovascular disease (CVD) risk factors have
      a strong association with obesity. Anthropometric indices have been widely used
      to evaluate obesity in clinical and epidemiological studies. We aim to
      investigate association between serum lipid levels and different anthropometric
      indices. METHODS: Our study included 17,554 participants. We mainly investigated
      area under the receiver operating characteristic (AUROC) curves and optimal
      operating points (OOPs) between the anthropometric indices and serum lipid levels
      or categories of abnormal serum lipid indices. RESULTS: For predicting one/two
      categories of abnormal serum lipid indices among the anthropometric indices,
      AUROC value of WC was the highest in men (0.718), and AUROC values of BRI and
      WHtR were the highest in women (0.700 and 0.700) (all P < 0.001); OOP of WC was
      82.450 in men; OOPs of BRI and WHtR were 3.435 and 0.504 in women. For predicting
      three/more categories of abnormal serum lipid indices among the anthropometric
      indices, AUROC value of WC was the highest in men (0.806), and AUROC values of
      BRI and WHtR were the highest in women (0.783 and 0.783) (all P < 0.001); OOP of
      WC was 84.150 in men; OOPs of BRI and WHtR were 3.926 and 0.529 in women.
      CONCLUSIONS: WC was a good predictor for one/two or three/more categories of
      abnormal serum lipid indices in men. However, BRI and WHtR were good predictors
      for one/two or three/more categories of abnormal serum lipid indices in women.
      ABSI showed the weakest predictive power.

PMID- 29357898
TI  - Serum vitamin D and vitamin D-binding protein levels in mother-neonate pairs
      during the lactation period.
AB  - BACKGROUND: To determine longitudinally the relationship between serum 25
      hydroxyvitamin D (vitamin D) and vitamin D-binding protein (DBP) levels in mother
      neonate pairs and evaluate the efficiency of prophylactic vitamin D on lactation
      days 45-60. METHODS: Mother-neonate pairs whose serum calcium (Ca), phosphorus
      (P), magnesium (Mg), alkaline phosphatase (ALP), and parathyroid hormone (PTH)
      levels were in normal ranges on postpartum/postnatal days 5-10 were classified
      into two groups by their serum vitamin D concentrations (Group A: < 10 ng/ml and
      Group B: > 20 ng/ml). Both maternal and neonatal Ca, P, Mg, ALP, and PTH
      concentrations in group A and B were not different. Maternal and neonatal serum
      DBP levels were measured in two groups. The mother-neonate pairs in both groups
      were given 400 IU/d vitamin D orally. The same biochemical markers in group A
      were remeasured on days 45-60 of the lactation period. RESULTS: In group A, the
      mean maternal and neonatal vitamin D levels on postpartum/postnatal days 5-10
      were significantly lower and the DBP levels were significantly higher than those
      in group B (P = 0.000; P = 0.000 and P = 0.04; P = 0.004, respectively). On
      lactation days 45-60, the maternal and neonatal DBP concentrations were not
      different from those on postpartum/postnatal days 5-10. However, the maternal and
      neonatal vitamin D levels were significantly increased (P = 0.000 and P = 0.000,
      respectively), while the neonatal PTH concentrations were significantly decreased
      (P = 0.000). The maternal and neonatal vitamin D concentrations were negatively
      correlated with their DBP concentrations (P = 0.048 and P = 0.002, respectively).
      CONCLUSION: High maternal and neonatal DBP levels may lead to an incorrect low
      estimate of the true Vitamin D concentration. In this case, only prophylactic
      vitamin D (400 IU/d) is indicated for mothers and their infants.

PMID- 29357899
TI  - Pediatric multi-drug resistant-tuberculosis and HIV co-infection in a resource
      limited setting: a case report.
AB  - BACKGROUND: Tuberculosis remains a major cause of morbidity and mortality
      worldwide, especially in developing countries. The diagnosis and treatment of
      multi-drug resistant tuberculosis (MDR-TB) in children remain a major limitation
      in this setting, largely due to difficulties in isolating Mycobacterium
      tuberculosis from pediatric specimens, management with toxic second line drugs,
      and practically the inexistence of contact tracing. In 2016, the World Health
      Organization (WHO) recommended a standardized 9-month regimen for adults and
      children in zones which are highly endemic for the human immunodeficiency virus
      (HIV). Herein, we present a case of pediatric MDR-TB/HIV co-infection
      highlighting the difficulties in treatment and the importance of contact tracing.
      CASE PRESENTATION: A 6-year old male infant from the West Region of Cameroon
      infected with HIV who presented at a local health center with a 10 days history
      of productive cough associated with nocturnal fever and abdominal pains non
      responsive to broad spectrum antibiotics. A sputum sample analysis requested was
      smear positive for acid-fast bacilli, and he was initiated on quadritherapy for
      drug sensitive pulmonary tuberculosis. Since he was a household contact of the
      mother who was being managed in a referral hospital for MDR-TB at 1 month of
      treatment, and given his critical clinical situation, a gastric aspirate was
      repeated and sent for Xpert MTB/RIF to the Tuberculosis Reference Laboratory
      which was positive for a Rifampicin resistant strain of M. tuberculosis. The
      short 9 months regimen against MDR-TB was then initiated. During the course of
      his management, he developed minor side effects of the drugs which were managed
      symptomatically. CONCLUSION: Even though pediatric MDR-TB is difficult to
      confirm, it can be treated with favorable clinical outcomes using the short
      regimen recommended by the WHO. Experts involved in the control of tuberculosis
      over the national territory should consider adopting routine contact tracing for
      all cases of tuberculosis particularly amongst children.

PMID- 29357897
TI  - Parkinson disease-associated mutations in LRRK2 cause centrosomal defects via
      Rab8a phosphorylation.
AB  - BACKGROUND: Mutations in LRRK2 are a common genetic cause of Parkinson's disease
      (PD). LRRK2 interacts with and phosphorylates a subset of Rab proteins including
      Rab8a, a protein which has been implicated in various centrosome-related events.
      However, the cellular consequences of such phosphorylation remain elusive.
      METHODS: Human neuroblastoma SH-SY5Y cells stably expressing wildtype or
      pathogenic LRRK2 were used to test for polarity defects in the context of
      centrosomal positioning. Centrosomal cohesion deficits were analyzed from
      transiently transfected HEK293T cells, as well as from two distinct peripheral
      cell types derived from LRRK2-PD patients. Kinase assays, coimmunoprecipitation
      and GTP binding/retention assays were used to address Rab8a phosphorylation by
      LRRK2 and its effects in vitro. Transient transfections and siRNA experiments
      were performed to probe for the implication of Rab8a and its phosphorylated form
      in the centrosomal deficits caused by pathogenic LRRK2. RESULTS: Here, we show
      that pathogenic LRRK2 causes deficits in centrosomal positioning with effects on
      neurite outgrowth, cell polarization and directed migration. Pathogenic LRRK2
      also causes deficits in centrosome cohesion which can be detected in peripheral
      cells derived from LRRK2-PD patients as compared to healthy controls, and which
      are reversed upon LRRK2 kinase inhibition. The centrosomal cohesion and polarity
      deficits can be mimicked when co-expressing wildtype LRRK2 with wildtype but not
      phospho-deficient Rab8a. The centrosomal defects induced by pathogenic LRRK2 are
      associated with a kinase activity-dependent increase in the centrosomal
      localization of phosphorylated Rab8a, and are prominently reduced upon RNAi of
      Rab8a. CONCLUSIONS: Our findings reveal a new function of LRRK2 mediated by Rab8a
      phosphorylation and related to various centrosomal defects.

PMID- 29357900
TI  - Insecticide resistance and target site mutations (G119S ace-1 and L1014F kdr) of
      Culex pipiens in Morocco.
AB  - BACKGROUND: Control of the mosquito vector Culex pipiens with insecticides is the
      main way to control arboviruses that the species can transmit such as West Nile
      virus (WNV) and Rift Valley fever virus (RVFV). However, its efficiency has been
      hampered by the emergence of insecticide resistance. Little is known about the
      insecticide-resistance status and underlying resistance mechanisms of field
      collected populations of Cx. pipiens in Morocco. METHODS: Mosquito adults from
      Mohammadia city in Morocco were reared from immature stages. The level of their
      susceptibility to insecticides was assessed using standard WHO bioassay. The two
      forms of the Cx. pipiens complex and their hybrids were identified by a multiplex
      PCR. Identified mosquitoes were then tested for the presence of the G119S ace-1
      and L1014F kdr mutations using PCR-RFLP and PCR assays, respectively. RESULTS:
      WHO bioassays indicated that Cx. pipiens was resistant to all tested
      insecticides: lambda-cyhalothrin (49% mortality), permethrin (63% mortality), DDT
      (16% mortality), malation (52% mortality) and bendiocarb (39% mortality). The
      frequency of the 119S allele was almost identical in the pipiens form and hybrids
      (0.11 and 0.15, respectively) whereas it remained low in the molestus form
      (0.03). No significant correlation was observed between the G119S allele and the
      resistance phenotype to two tested insecticides (malathion and bendiocarb). The
      frequency of the L1014F allele was identical in the pipiens form and hybrids
      (0.44) whereas it was low in the molestus form (0.36) but no significant
      difference was detected (chi2 = 1.46, df = 1, P = 0.225). The presence of the
      L1014F kdr mutation was significantly associated with resistance to three tested
      insecticides in pipiens form (P = 0.0019, P = 0.0023 and P = 0.023, respectively,
      to lambda-cyhalothrin, permethrin and DDT) whereas no significant correlation was
      observed between the L1014F kdr mutation and resistance phenotype in molestus
      form and hybrids to the three tested insecticides. CONCLUSION: These findings
      showed that wild populations of Cx. pipiens have developed resistance against the
      main insecticide families with different modes of action: organochlorines (DDT),
      organophosphates (malathion), carbamates (bendiocarb), pyrethroids (lambda
      cyhalothrin, permethrin). Therefore, urgent action should be taken to manage the
      resistance in this species to maintain the effectiveness of arbovirus control.

PMID- 29357901
TI  - Can artificial tears prevent Acanthamoeba keratitis? An in vitro approach.
AB  - BACKGROUND: The use of contact lenses has increased in recent years as has the
      incidence of Dry Eye Syndrome, partly due to their use. Artificial tears are the
      most common treatment option. Since these changes can facilitate Acanthamoeba
      infection, the present study has been designed to evaluate the effect of three
      artificial tears treatments in the viability of Acanthamoeba genotype T4
      trophozoites. Optava FusionTM, Oculotect(r), and Artelac(r) Splash were selected
      due to their formulation. METHODS: Viability was assessed using two staining
      methods, Trypan Blue stain and CTC stain at different time intervals (2, 4, 6, 8
      and 24 h). Trypan Blue viability was obtained by manual count with light
      microscopy while the CTC stain was determined using flow cytometry. RESULTS:
      Trypan Blue staining results demonstrated a decrease in viability for Optava
      FusionTM and Artelac(r) Splash during the first 4 h of incubation. After, this
      effect seems to lose strength. In the case of Oculotect(r), complete cell death
      was observed after 2 h. Using flow cytometry analysis, Optava FusionTM and
      Oculotect(r) exhibited the same effect observed with Trypan Blue staining.
      However, Artelac(r) Splash revealed decreasing cell respiratory activity after
      four hours, with no damage to the cell membrane. CONCLUSIONS: The present study
      uses, for the first time, CTC stain analyzed by flow cytometry to establish
      Acanthamoeba viability demonstrating its usefulness and complementarity with the
      traditional stain, Trypan Blue. Artelac(r) Splash, with no preservatives, and
      Optava Fusion TM, with Purite(r), have not shown any useful amoebicidal activity.
      On the contrary, promising results presented by Ocultect(r), with BAK, open up a
      new possibility for Acanthamoeba keratitis prophylaxis and treatment although in
      vivo studies should be carried out.

PMID- 29357902
TI  - Intensity-modulated radiotherapy with integrated-boost in patients with bone
      metastasis of the spine: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Stereotactic body radiation therapy (SBRT) using intensity-modulated
      radiotherapy (IMRT) with dose escalation by simultaneous integrated boost (SIB)
      can be a safe modality for treating spinal bone metastases with enhanced
      targeting accuracy and improve local tumor control. METHODS/DESIGN: This is a
      single-center, prospective, randomized, controlled trial. One hundred and twenty
      patients with spinal bone metastases will receive palliative radiation therapy at
      the Heidelberg University Hospital. SBRT will be given in five or ten fractions
      with or without SIB. Four treatment arms are planned: IMRT with 30 Gy in ten
      fractions, IMRT with 30 Gy in ten fractions and SIB to 40 Gy, IMRT with 20 Gy in
      five fractions, and IMRT with 20 Gy in five fractions and SIB to 30Gy in five
      fractions will be compared. The target parameters will be measured at baseline
      level and at three and six months after radiation. DISCUSSION: The primary
      endpoint of this study was to assess and compare the local tumor control (by
      means of different fractionation schedules and biological doses to the tumor
      area). Secondary endpoints are acute and chronic adverse events, pain relief,
      quality of life, and fatigue. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02832765
      . Registered on 27 July 2016.

PMID- 29357903
TI  - Principles for interactions with biopharmaceutical companies: the development of
      guidelines for patient advocacy organizations in the field of rare diseases.
AB  - BACKGROUND: Rare diseases are a global public health concern, affecting an
      estimated 350 million individuals. Only 5% of approximately 7000 known rare
      diseases have a treatment, and only about half have a patient advocacy
      organization. Biopharmaceutical companies face complex challenges in developing
      treatments for rare diseases. Patient advocacy organizations may play a major
      role by positively influencing research and development, clinical trials, and
      regulations. Thus, collaboration among patient advocacy organizations and
      industry is essential to bring new therapeutics to patients. METHODS: We
      identified an unmet need for guidelines on day-to-day decision-making by rare
      disease patient advocacy organizations when working with biopharmaceutical
      partners. We convened an Independent Expert Panel experienced in collaborations
      between patient advocacy organizations and biopharmaceutical companies (April
      2017) to develop consensus guidelines for these relationships. The guidelines
      were based on an original version by the International Fibrodysplasia Ossificans
      Progressiva Association (IFOPA). The Expert Panel reviewed and broadened these to
      be applicable to all patient advocacy organizations. Comments on the draft
      Guidelines were provided first by Panel participants and subsequently by six
      independent experts from patient advocacy organizations and industry. RESULTS:
      The Panel comprised four experts from the rare disease community who lead patient
      advocacy organizations; three leaders who perform advocacy functions within
      biopharmaceutical companies; and two facilitators, both having leadership
      experience in rare diseases and industry. The finalized Guidelines consist of
      four main sections: Identification and Engagement With Companies, Patient
      Engagement and Patient Privacy, Financial Contributions, and Clinical Trial
      Communication and Support. The Guidelines address the daily considerations,
      choices, and consequences of patient advocacy organizations as they engage with
      biopharmaceutical companies, and offer recommendations for volunteer/paid leaders
      of the organizations on how to interact in a thoughtful, responsible, ethical way
      that engenders trust. CONCLUSIONS: These Guidelines recommend best practices and
      standards for interactions between patient advocacy organizations and industry
      that will ultimately have a positive effect on the development of novel
      treatments. Patient advocacy organizations will be provided free access to these
      Guidelines to help bring clarification to day-to-day decision-making around their
      interactions, and for use as a living document with the potential for regular
      revisions and updates.

PMID- 29357904
TI  - Implementation of patient pagers in radiation oncology waiting rooms for patient
      privacy and satisfaction.
AB  - OBJECTIVE: In order to improve privacy, quality, and coordination of care, a
      patient pager system was introduced to notify patients of daily treatment in the
      Department of Radiation Oncology. One hundred patients undergoing daily radiation
      therapy prospectively participated in a six-question survey addressing the paging
      service, privacy prior to pager use, and demographics. Twelve radiation
      therapists also participated in a survey addressing privacy and workflow.
      RESULTS: Survey results from all patient participants revealed that convenience,
      privacy, ease of use, desire for use for consults and return visits were highly
      rated as very good to excellent. The top three categories were "ease of use,"
      "convenience" and "privacy." Nineteen patients had the experience of our waiting
      room prior to introduction of the patient pagers and highly rated "privacy,"
      "efficiency," and "satisfaction." Twelve radiation therapists participated and
      rated workflow related categories fair to good. Only patient privacy was rated as
      very good to excellent. Thus, patients and staff highly rated the paging system
      for privacy protection and satisfaction. However, it did not change overall
      workflow. Our study shows clinics should prioritize privacy in the waiting room
      to address the emotional needs of patients and improve satisfaction.

PMID- 29357907
TI  - Measuring improvement in fracture risk prediction for a new risk factor: a
      simulation.
AB  - OBJECTIVE: Improvements in clinical risk prediction models for osteoporosis
      related fracture can be evaluated using area under the receiver operating
      characteristic (AUROC) curve and calibration, as well as reclassification
      statistics such as the net reclassification improvement (NRI) and integrated
      discrimination improvement (IDI) statistics. Our objective was to compare the
      performance of these measures for assessing improvements to an existing fracture
      risk prediction model. We simulated the effect of a new, randomly-generated risk
      factor on prediction of major osteoporotic fracture (MOF) for the internationally
      validated FRAX(r) model in a cohort from the Manitoba Bone Mineral Density (BMD)
      Registry. RESULTS: The study cohort was comprised of 31,999 women 50+ years of
      age; 9.9% sustained at least one MOF in a mean follow-up of 8.4 years. The
      original prediction model had good discriminative performance, with AUROC = 0.706
      and calibration (ratio of observed to predicted risk) of 0.990. The addition of
      the simulated risk factor resulted in improvements in NRI and IDI for most
      investigated conditions, while AUROC decreased and changes in calibration were
      negative. Reclassification measures may give different information than
      discrimination and calibration about the performance of new clinical risk
      factors.

PMID- 29357905
TI  - Chromosome-nuclear envelope attachments affect interphase chromosome territories
      and entanglement.
AB  - BACKGROUND: It is well recognized that the interphase chromatin of higher
      eukaryotes folds into non-random configurations forming territories within the
      nucleus. Chromosome territories have biologically significant properties, and
      understanding how these properties change with time during lifetime of the cell
      is important. Chromosome-nuclear envelope (Chr-NE) interactions play a role in
      epigenetic regulation of DNA replication, repair, and transcription. However,
      their role in maintaining chromosome territories remains unclear. RESULTS: We use
      coarse-grained molecular dynamics simulations to study the effects of Chr-NE
      interactions on the dynamics of chromosomes within a model of the Drosophila
      melanogaster regular (non-polytene) interphase nucleus, on timescales comparable
      to the duration of interphase. The model simulates the dynamics of chromosomes
      bounded by the NE. Initially, the chromosomes in the model are prearranged in
      fractal-like configurations with physical parameters such as nucleus size and
      chromosome persistence length taken directly from experiment. Time evolution of
      several key observables that characterize the chromosomes is quantified during
      each simulation: chromosome territories, chromosome entanglement, compactness,
      and presence of the Rabl (polarized) chromosome arrangement. We find that Chr-NE
      interactions help maintain chromosome territories by slowing down and limiting,
      but not eliminating, chromosome entanglement on biologically relevant timescales.
      At the same time, Chr-NE interactions have little effect on the Rabl chromosome
      arrangement as well as on how chromosome compactness changes with time. These
      results are rationalized by simple dimensionality arguments, robust to model
      details. All results are robust to the simulated activity of topoisomerase, which
      may be present in the interphase cell nucleus. CONCLUSIONS: Our study
      demonstrates that Chr-NE attachments may help maintain chromosome territories,
      while slowing down and limiting chromosome entanglement on biologically relevant
      timescales. However, Chr-NE attachments have little effect on chromosome
      compactness or the Rabl chromosome arrangement.

PMID- 29357906
TI  - Body mass index at age 18 years and recent body mass index in relation to risk of
      breast cancer overall and ER/PR/HER2-defined subtypes in white women and African
      American women: a pooled analysis.
AB  - BACKGROUND: Although it has been well-documented that obesity is associated with
      decreased risk of premenopausal breast cancer and increased risk of
      postmenopausal breast cancer, it is unclear whether these associations differ
      among breast cancer subtypes defined by the tumor protein expression status of
      estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth
      factor receptor 2 (HER2). METHODS: We evaluated the associations of body mass
      index (BMI) at age 18 years and recent BMI in relation to risk of breast cancer
      overall and ER/PR/HER2-defined subtypes, in 6320 women (3934 case-patient
      participants, 2386 control participants) aged 35-64 years, who participated in
      one of three population-based case-control studies. We estimated multivariable
      adjusted odd ratios (ORs) and corresponding 95% confidence intervals (CIs) using
      polychotomous unconditional logistic regression methods for case-control
      comparisons in premenopausal women and postmenopausal women. RESULTS: BMI at age
      18 years was inversely associated with risk of breast cancer, particularly among
      premenopausal women (>= 25 vs. < 20 kg/m2, OR = 0.72, 95% CI = 0.53-0.96; per 5
      kg/m2 increase, OR = 0.83, 95% CI = 0.73-0.95). This inverse association did not
      differ across ER/PR/HER2-defined subtypes or by race (white women, African
      American women). Recent BMI was not associated with risk of premenopausal breast
      cancer after adjustment for BMI at age 18 years; nevertheless, the analysis for
      the joint effects of BMI at age 18 years and recent BMI showed that premenopausal
      women in the highest categories of the two BMI measures (>= 25 kg/m2 at age 18
      years and >= 30 kg/m2 for recent BMI) had 46% lower risk of breast cancer than
      premenopausal women in the lowest categories of the two BMI measures (< 20 kg/m2
      at age 18 years and < 25 kg/m2 for recent BMI; OR = 0.54, 95% CI = 0.38-0.78).
      Neither measure of BMI was statistically significantly associated with risk of
      postmenopausal breast cancer. CONCLUSION: Our findings indicate that high BMI
      near the end of adolescence decreases risk of all ER/PR/HER2-defined subtypes of
      premenopausal breast cancer and also suggest that this benefit could be maximized
      among premenopausal women who consistently have high BMI during their
      premenopausal years.

PMID- 29357908
TI  - Single and combined use of red cell distribution width, mean platelet volume, and
      cancer antigen 125 for differential diagnosis of ovarian cancer and benign
      ovarian tumors.
AB  - BACKGROUND: Cancer is widely believed to result from chronic inflammation, and
      red cell distribution width (RDW) and mean platelet volume (MPV) are considered
      as inflammatory markers for cancer. We investigated the values of RDW, MPV, and
      cancer antigen 125 (CA125), alone or in combination, for distinguishing between
      ovarian cancer and benign ovarian tumors. METHODS: The study included 326
      patients with ovarian cancer, 290 patients with benign ovarian tumors, and 162
      control subjects. Hematologic tests were performed at initial diagnosis. RESULTS:
      RDW was increased and MPV was decreased in the ovarian cancer group compared with
      the control and benign ovarian tumor groups. RDW was positively correlated and
      MPV was negatively correlated with cancer stage. Area under the curve (AUC)
      analysis for ovarian cancer versus benign ovarian tumors revealed that the
      specificity and sensitivity were increased for the combination of MPV and CA125
      compared with either marker alone, and the specificity was increased for the
      combination of RDW and CA125, compared with either alone. The AUCs for RDW plus
      CA125 and MPV plus CA125 were significantly larger than for any of the markers
      alone. CONCLUSIONS: In conclusion, combinations of the markers RDW, MPV, and
      CA125 may improve the differential diagnosis of ovarian cancer and benign ovarian
      tumors.

PMID- 29357909
TI  - Size and sequence polymorphisms in the glutamate-rich protein gene of the human
      malaria parasite Plasmodium falciparum in Thailand.
AB  - BACKGROUND: The glutamate-rich protein (GLURP) of the malaria parasite Plasmodium
      falciparum is a key surface antigen that serves as a component of a clinical
      vaccine. Moreover, the GLURP gene is also employed routinely as a genetic marker
      for malarial genotyping in epidemiological studies. While extensive size
      polymorphisms in GLURP are well recorded, the extent of the sequence diversity of
      this gene is rarely investigated. The present study aimed to explore the genetic
      diversity of GLURP in natural populations of P. falciparum. RESULTS: The
      polymorphic C-terminal repetitive R2 region of GLURP sequences from 65 P.
      falciparum isolates in Thailand were generated and combined with the data from
      103 worldwide isolates to generate a GLURP database. The collection was comprised
      of 168 alleles, encoding 105 unique GLURP subtypes, characterized by 18 types of
      amino acid repeat units (AAU). Of these, 28 GLURP subtypes, formed by 10 AAU
      types, were detected in P. falciparum in Thailand. Among them, 19 GLURP subtypes
      and 2 AAU types are described for the first time in the Thai parasite population.
      The AAU sequences were highly conserved, which is likely due to negative
      selection. Standard Fst analysis revealed the shared distributions of GLURP types
      among the P. falciparum populations, providing evidence of gene flow among the
      different demographic populations. CONCLUSIONS: Sequence diversity causing size
      variations in GLURP in Thai P. falciparum populations were detected, and caused
      by non-synonymous substitutions in repeat units and some insertion/deletion of
      aspartic acid or glutamic acid codons between repeat units. The P. falciparum
      population structure based on GLURP showed promising implications for the
      development of GLURP-based vaccines and for monitoring vaccine efficacy.

PMID- 29357910
TI  - A synthetic cell-penetrating peptide derived from nuclear localization signal of
      EPS8 exerts anticancer activity against acute myeloid leukemia.
AB  - BACKGROUND: Oncogenic roles of epidermal growth factor receptor pathway substrate
      no.8 (EPS8) have been widely reported in various tumors, making targeting of EPS8
      an appealing prospect. Here, we describe the role of EPS8 in acute myeloid
      leukemia (AML) and consider the potential of EPS8 as an anti-AML target. Nuclear
      localization signal (NLS) residues of tumor-associated proteins are crucial for
      cell cycle progression, and specific inhibitors derived from the NLS have
      inhibitory effect on cancer cells. The NLS in EPS8 has potential as a specific
      anti-AML target. METHODS: Gene Expression Omnibus expression profiles of AML
      patients were used to test associations between EPS8 expression and AML patient
      outcome. The biological characteristics of AML cells after EPS8 knockdown were
      analyzed in vitro and in vivo. A specific peptide (CP-EPS8-NLS) derived from the
      NLS of EPS8 (amino acids 298-310) was synthesized, and the anti-AML effects of CP
      EPS8-NLS were analyzed in cancer cells and in xenograft models. Mutated CP-EPS8
      NLS and penetratin served as controls. RESULTS: We observed that elevated EPS8
      expression in AML patients is associated with poor outcome. Knockdown of EPS8
      significantly suppressed the survival of AML cells in vitro and in vivo. CP-EPS8
      NLS interfered with EPS8-associated signaling and consequently exerted anti-AML
      activity. Importantly, CP-EPS8-NLS displayed anti-AML activity in various AML
      cell types, with diminished activity in PBMCs. CP-ESP8-NLS suppressed U937 cell
      proliferation, and injection of CP-EPS8-NLS exerted potent antitumor activity in
      the xenograft tumor models. A synergistic effect of CP-EPS8-NLS and
      chemotherapeutic agents was also observed in vitro and in vivo. Mechanistically,
      treatment of various AML cells with CP-EPS8-NLS downregulated the expression of
      EPS8 and its downstream pathways. CONCLUSIONS: The function of CP-EPS8-NLS is
      explained by the presence of a NLS in EPS8, which has been shown to induce
      nuclear translocation, consequently resulting in EPS8 overexpression. These
      results indicate that EPS8 is a potential target for AML treatment.

PMID- 29357912
TI  - eRegQual-an electronic health registry with interactive checklists and clinical
      decision support for improving quality of antenatal care: study protocol for a
      cluster randomized trial.
AB  - BACKGROUND: Health worker compliance with established best-practice clinical and
      public health guidelines may be enhanced by customized checklists of care and
      clinical decision support driven by point-of-care data entry into an electronic
      health registry. The public health system of Palestine is currently implementing
      a national electronic registry (eRegistry) for maternal and child health. This
      trial is embedded in the national implementation and aims to assess the
      effectiveness of the eRegistry's interactive checklists and clinical decision
      support, compared with the existing paper based records, on improving the quality
      of care for pregnant women. METHODS: This two-arm cluster randomized controlled
      trial is conducted in the West Bank, Palestine, and includes 120 clusters
      (primary healthcare clinics) with an average annual enrollment of 60 pregnancies.
      The intervention tool is the eRegistry's interactive checklists and clinical
      decision support implemented within the District Health Information System 2
      (DHIS2) Tracker software, developed and customized for the Palestinian context.
      The primary outcomes reflect the processes of essential interventions, namely
      timely and appropriate screening and management of: 1) anemia in pregnancy; 2)
      hypertension in pregnancy; 3) abnormal fetal growth; 4) and diabetes mellitus in
      pregnancy. The composite primary health outcome encompasses five conditions
      representing risk for the mother or baby that could have been detected or
      prevented by high-quality antenatal care: moderate or severe anemia at admission
      for labor; severe hypertension at admission for labor; malpresentation at
      delivery undetected during pregnancy; small for gestational age baby at delivery
      undetected during pregnancy; and large for gestational age baby at delivery.
      Primary analysis at the individual level taking the design effect of the
      clustering into account will be performed as intention-to-treat. DISCUSSION: This
      trial, embedded in the national implementation of the eRegistry in Palestine,
      allows the assessment of process and health outcomes in a large-scale pragmatic
      setting. Findings will inform the use of interactive checklists and clinical
      decision support driven by point-of-care data entry into an eRegistry as a health
      systems-strengthening approach. TRIAL REGISTRATION: ISRCTN trial registration
      number, ISRCTN18008445 . Registered on 6 April 2017.

PMID- 29357911
TI  - Comparative genomics analysis of triatomines reveals common first line and
      inducible immunity-related genes and the absence of Imd canonical components
      among hemimetabolous arthropods.
AB  - BACKGROUND: Insects operate complex humoral and cellular immune strategies to
      fend against invading microorganisms. The majority of these have been
      characterized in Drosophila and other dipterans. Information on hemipterans,
      including Triatominae vectors of Chagas disease remains incomplete and
      fractionated. RESULTS: We identified putative immune-related homologs of three
      Triatominae vectors of Chagas disease, Triatoma pallidipennis, T. dimidiata and
      T. infestans (TTTs), using comparative transcriptomics based on established
      immune response gene references, in conjunction with the predicted proteomes of
      Rhodnius prolixus, Cimex lecticularis and Acyrthosiphon pisum hemimetabolous. We
      present a compressive description of the humoral and cellular innate immune
      components of these TTTs and extend the immune information of other related
      hemipterans. Key homologs of the constitutive and induced immunity genes were
      identified in all the studied hemipterans. CONCLUSIONS: Our results in the TTTs
      extend previous observations in other hemipterans lacking several components of
      the Imd signaling pathway. Comparison with other hexapods, using published data,
      revealed that the absence of various Imd canonical components is common in
      several hemimetabolous species.

PMID- 29357913
TI  - Screening of methicillin-resistant Staphylococcus aureus nasal colonization among
      elective surgery patients in referral hospital in Indonesia.
AB  - OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is
      associated with serious surgical site infection in high-risk patients. High
      prevalence of MRSA colonization was reported in many settings, nonetheless local
      data is required. The purpose of this study is to identify the prevalence and
      risk factor of MRSA nasal carriage in adult patients in National Referral
      Hospital in Indonesia before underwent elective surgical procedure. RESULTS: From
      384 patients, 16.9% patients of them had undergone orthopaedic surgery, 51.3% had
      received antibiotics within the previous 3-month and 41.1% patients had history
      of hospitalization within the previous 1 year. Total of 21.6% patients were on
      invasive devices for at least 48 h before the operation; 24.2% had an open wound;
      19.3% patients were referred from other hospital/ward. Of these patients, solid
      tumor without metastasis was the most common factor identified by the Charlson
      index (38.3%). Nasal colonization of Gram-positive bacteria was detected in
      76.8%; S. aureus in 15.6% of patients (n = 60). MRSA was identified in three
      isolates (0.8%) by both culture and polymerase chain reaction (PCR) tests. Due to
      low prevalence of MRSA nasal carriage, this finding supports the recommendation
      to not routinely apply mupirocin for nasal decolonization on patient planned for
      surgery in Indonesia.

PMID- 29357915
TI  - Evaluation of HbA1c screening during outreach events for prediabetes subject
      recruitment for clinical research.
AB  - BACKGROUND: There are a number of obstacles which may impede the recruitment of
      underserved populations in clinical research studies; some of these factors
      include mistrust of medical research, socioeconomic constraints, cultural
      factors, and language barriers. For chronic metabolic disease indications, these
      barriers may also include lack of disease awareness. Recently, national
      organizations such as the American Diabetes Association (ADA) and Centers for
      Disease Control and Prevention (CDC) have highlighted the need for prediabetes
      recognition. Therefore the aim of the study was twofold: to raise prediabetes
      awareness in an under-represented Hispanic community and to engage prediabetes
      participants in clinical research. METHODS: Hemoglobin A1c (HbA1c) screening was
      performed at major outreach events catered to the Hispanic community. All
      participants signed an ethics review board approved waiver which collected basic
      demographic information and the HbA1c test was performed with a hand-held monitor
      and finger-stick blood sample. Participants were given their HbA1c results at the
      event as well as information on prediabetes and upcoming clinic studies. After
      the event, participants were contacted by a study participant recruiter to assess
      interest in participating in clinical research. RESULTS: The majority of
      participants screened fell within a prediabetes HbA1c range. Mean HbA1c was
      similar among men and women, yet higher in individuals aged 45-65 years compared
      to adults aged < 45 years (p < 0.05). For recruitment purposes, the highest
      number of leads came from participants attending a faith-based community event.
      In all, 17% of individuals contacted expressed interest in participating in
      clinical research and created a profile within our database to be eligible for
      future studies. CONCLUSIONS: Providing no-cost HbA1c screening is an excellent
      recruitment tool for clinical research as well as an opportunity to raise
      prediabetes awareness in a traditionally underserved population.

PMID- 29357914
TI  - Cell adhesion-mediated mitochondria transfer contributes to mesenchymal stem cell
      induced chemoresistance on T cell acute lymphoblastic leukemia cells.
AB  - BACKGROUND: Despite the high cure rate of T cell acute lymphoblastic leukemia (T
      ALL), drug resistance to chemotherapy remains a significant clinical problem.
      Bone marrow mesenchymal stem cells (MSCs) protect leukemic cells from
      chemotherapy, but the underlying mechanisms are poorly understood. In this study,
      we aimed to uncover the mechanism of MSC-induced chemoresistance in T-ALL cells,
      thus providing a promising clinical therapy target. METHODS: Cell viability was
      determined using the viability assay kit CCK-8. The mitochondrial ROS levels were
      detected using the fluorescent probe MitoSOXTM Red, and fluorescence intensity
      was measured by flow cytometry. In vitro, MSCs and Jurkat cells were cocultured.
      MSCs were labeled with green fluorescent protein (GFP), and Jurkat cells were
      labeled with the mitochondria-specific dye MitoTracker Red. Bidirectional
      mitochondrial transfer was detected by flow cytometry and confocal microscopy.
      The mechanism of mitochondria transfer was analyzed by inhibitor assays.
      Transcripts related to Jurkat cell/MSC adhesion in the coculture system were
      assessed by qRT-PCR. After treatment with a neutralizing antibody against a key
      adhesion molecule, mitochondria transfer from Jurkat cells to MSCs was again
      detected by flow cytometry and confocal microscopy. Finally, we verified our
      findings using human primary T-ALL cells cocultured with MSCs. RESULTS:
      Chemotherapeutic drugs caused intracellular oxidative stress in Jurkat cells.
      Jurkat cells transfer mitochondria to MSCs but receive few mitochondria from
      MSCs, resulting in chemoresistance. This process of mitochondria transfer is
      mediated by tunneling nanotubes, which are protrusions that extend from the cell
      membrane . Moreover, we found that most Jurkat cells adhered to MSCs in the
      coculture system, which was mediated by the adhesion molecule ICAM-1. Treatment
      with a neutralizing antibody against ICAM-1 led to a decreased number of adhering
      Jurkat cells, decreased mitochondria transfer, and increased chemotherapy-induced
      cell death. CONCLUSIONS: We show evidence that mitochondria transfer from Jurkat
      cells to MSCs, which is mediated by cell adhesion, may be a potential therapeutic
      target for T-ALL treatment.

PMID- 29357916
TI  - Anti-tumor effects of ONC201 in combination with VEGF-inhibitors significantly
      impacts colorectal cancer growth and survival in vivo through complementary non
      overlapping mechanisms.
AB  - BACKGROUND: Small molecule ONC201 is an investigational anti-tumor agent that
      upregulates intra-tumoral TRAIL expression and the integrated stress response
      pathway. A Phase I clinical trial using ONC201 therapy in advanced cancer
      patients has been completed and the drug has progressed into Phase II trials in
      several cancer types. Colorectal cancer (CRC) remains one of the leading causes
      of cancer worldwide and metastatic disease has a poor prognosis. Clinical trials
      in CRC and other tumor types have demonstrated that therapeutics targeting the
      vascular endothelial growth factor (VEGF) pathway, such as bevacizumab, are
      effective in combination with certain chemotherapeutic agents. METHODS: We
      investigated the potential combination of VEGF inhibitors such as bevacizumab and
      its murine-counterpart; along with other anti-angiogenic agents and ONC201 in
      both CRC xenograft and patient-derived xenograft (PDX) models. We utilized non
      invasive imaging and immunohistochemistry to determine potential mechanisms of
      action. RESULTS: Our results demonstrate significant tumor regression or complete
      tumor ablation in human xenografts with the combination of ONC201 with
      bevacizumab, and in syngeneic MC38 colorectal cancer xenografts using a murine
      VEGF-A inhibitor. Imaging demonstrated the impact of this combination on
      decreasing tumor growth and tumor metastasis. Our results indicate that ONC201
      and anti-angiogenic agents act through distinct mechanisms while increasing tumor
      cell death and inhibiting proliferation. CONCLUSION: With the use of both a
      murine VEGF inhibitor in syngeneic models, and bevacizumab in human cell line
      derived xenografts, we demonstrate that ONC201 in combination with anti
      angiogenic therapies such as bevacizumab represents a promising approach for
      further testing in the clinic for the treatment of CRC.

PMID- 29357917
TI  - Prevalence of intestinal parasitic infections in children under the age of 5
      years attending the Debre Birhan referral hospital, North Shoa, Ethiopia.
AB  - OBJECTIVE: Intestinal parasitic infection is one of the major childhood health
      problems in developing countries. In Ethiopia, epidemiological data for several
      localities is limited. Hence, the aim of this study is to assess intestinal
      parasitic infections among under-five children attending in Debre Birhan referral
      hospital, which could help to decrease morbidity and mortality in children. A
      cross-sectional study was conducted in February, 2014. Stool specimens were
      collected and examined using concentration method. RESULTS: Out of the 247 under
      five children participated, 17.4% (95% CI 12.7-22.1%) of the children were
      infected with at least one or more protozoa parasites (14.2% [95% CI 9.9-18.5%])
      and helminthes (3.2% [95% CI 1.0-5.4%]). Giardia lamblia (8.5%), Entamoeba
      histolytica/dispar (5.7%), Trichuris trichiura (1.6%) and Ascaris lumbricoides
      (1.2%) were the most identified parasites. Parasitic infection was higher in
      children who had source of drinking water from the river (36.8%), among children
      from mothers with poor hand washing practice (31.7%), and among children born
      from illiterate mothers (27.5%). This revealed that intestinal parasites affect
      the health of under-five children in the setting. Hence, improving environmental
      hygiene and inadequate water sanitation, and health education for behavioral
      changes to personal hygiene would be crucial for effective control of the
      parasite infections.

PMID- 29357918
TI  - Internet-based cognitive behavioural therapy (iCBT) for perinatal anxiety and
      depression versus treatment as usual: study protocol for two randomised
      controlled trials.
AB  - BACKGROUND: We aimed to evaluate the acceptability and efficacy of two brief,
      Internet-delivered cognitive behavioural therapy interventions-MUMentum Pregnancy
      (study 1) and MUMentum Postnatal (study 2)-in reducing maternal symptoms of
      anxiety, depression and overall psychological distress compared to usual care in
      the perinatal period. METHODS/DESIGN: Women who are pregnant (study 1) or < 12
      months postpartum (study 2) with current clinically elevated symptoms of anxiety
      and/or depression according to validated self-report measures, will be recruited
      via the research arm of a not-for-profit clinical and research unit in Australia
      and randomised to the intervention group or treatment as usual control group. The
      minimum sample size for each study (alpha 0.05; power 0.80 for a g of 0.80) was
      identified as 50 with at least 10% more to be recruited to account for expected
      attrition. The co-primary outcome measures are the Patient Health Questionnaire 9
      item scale and Generalised Anxiety Disorder 7-item scale to measure depression
      and anxiety symptom severity, respectively, and will be administered at the
      following primary time-points: baseline; post treatment; and at one-month follow
      up. Psychological distress will be measured according to the Kessler-10
      psychological distress scale at each primary time-point and will also be
      completed before each lesson for those in the intervention group. The total trial
      period nine weeks for study 1 and 11 weeks for study 2. Program efficacy will be
      determined using intent-to-treat mixed models. Maintenance of gains will be
      assessed at one-month follow-up. DISCUSSION: The current randomised controlled
      trial seeks to extend the literature by evaluating the efficacy of a self-help
      intervention for women in the perinatal period. If efficacious, the MUMentum
      programs have the potential to be easily disseminated via
      https://thiswayup.org.au/ to large numbers of women across Australia as an
      intervention for women screening positive for anxiety, depressive or distress
      symptoms during pregnancy or postpartum. TRIAL REGISTRATION: Australian New
      Zealand Clinical Trials Registry, ACTRN12616000560493 ; ACTRN12616000559415 .
      Registered on 2nd May 2016.

PMID- 29357919
TI  - MCM6 promotes metastasis of hepatocellular carcinoma via MEK/ERK pathway and
      serves as a novel serum biomarker for early recurrence.
AB  - BACKGROUND: The high incidence of recurrence and metastasis of hepatocellular
      carcinoma (HCC) necessitate the discovery of new predictive biomarkers of
      invasion and prognosis. Minichromosome maintenance complex component 6 (MCM6),
      which has been reported to up-regulate in multiple malignancies, was considered
      to be a novel diagnoses biomarker in HCC. However, its functional contributions
      and prognostic value remain unclear. METHODS: The expression of MCM6 was analyzed
      in 70 HCC tissues and 5 HCC cell lines by immunohistochemistry and real-time RT
      PCR. The roles of MCM6 in HCC cell proliferation, migration and invasion were
      explored by CCK8, Wound healing and Transwell assays, respectively. Western
      blotting and Immunofluorescence staining were conducted to detect the protein
      expressions of ERK signaling pathway and EMT-related markers. To verify the above
      findings in vivo, we established subcutaneous xenograft tumor and orthotopic
      xenograft tumor models in nude mice. Finally, Enzyme-linked immunosorbent assay
      was used to evaluate the serum MCM6 level. RESULTS: MCM6 was significantly up
      regulated in HCC tissues. Increased MCM6 expression was associated with
      aggressive clinicopathological features and worse prognosis in HCC patients.
      These results were consistent with our analyses of The Cancer Genome Atlas
      database (TCGA). Furthermore, knockdown of MCM6 significantly decreased
      proliferative and migratory/invasive capability of HCC cells in vitro, as well as
      decreased tumor volume, weight and the number of pulmonary metastases in vivo.
      Mechanistic analyses indicated that MCM6 promoted EMT and activated MEK/ERK
      signaling. More importantly, serum MCM6 levels in HCC patients were significantly
      higher than those in cirrhosis and healthy controls (P < 0.0001), and allowed
      distinguishing early recurrence with high accuracy (AUC = 0.773). CONCLUSIONS:
      Our findings indicate that MCM6 predicts poor prognosis and promotes metastasis
      in HCC. Postoperative serum MCM6 level could be valuable to detect preclinical
      early recurrence, indicative of a need for more careful surveillance and
      aggressive therapeutic intervention.

PMID- 29357920
TI  - Establishment of hematological reference intervals for healthy adults in Asmara.
AB  - OBJECTIVES: Clinical laboratory reference intervals used in a specific area
      should be derived from the local population as they are influenced by many
      factors. The purpose of this quantitative cross sectional study was to establish
      hematological reference intervals for healthy adults in Asmara and to determine
      whether the currently used reference interval do represent the adult population
      in the city. In addition, the established reference intervals were compared to
      findings from similar studies conducted in selected countries in Africa. RESULTS:
      There was a significant difference between males and females in the reference
      intervals for erythrocyte count, hemoglobin, hematocrit, mean cell volume, mean
      cell hemoglobin, mean cell hemoglobin concentration and differential white blood
      cell count. All the evaluated hematological analytes were found to be higher in
      males than in females except for platelet count. The out of range percentage for
      the parameters extends from 3.5 to 46.7%; with red blood cell count having the
      lowest while mean cell volume having the highest out of range percentage. The
      results indicated that the currently used reference interval does not represent
      the population in Asmara and are different from those obtained elsewhere in
      Africa.

PMID- 29357921
TI  - Relating process evaluation measures to complex intervention outcomes: findings
      from the PACE-UP primary care pedometer-based walking trial.
AB  - BACKGROUND: The PACE-UP trial demonstrated positive effects of a pedometer-based
      walking intervention on objective physical activity (PA) outcomes at three and 12
      months in 45-75-year-old primary care patients, in postal and nurse-supported
      trial arms compared with controls. We explored associations between process
      evaluation measures and change in PA outcomes. METHODS: The MRC framework guided
      process evaluation. Three quantitative measures (nurse session attendance [dose
      delivered], PA diary completion [fidelity] and pedometer use [fidelity]) were
      selected as independent variables in multi-level models estimating intervention
      effectiveness on PA outcomes (changes in step-counts and time in moderate-to
      vigorous PA [MVPA] levels in >= 10-min bouts). RESULTS: Dose: attending all three
      nurse sessions compared with 0-2 sessions was associated with an increase in
      steps/day at three and 12 months of 1197 (95% confidence interval [CI] = 627
      1766) and 605 (95% CI = 74-1137), respectively; and MVPA in bouts (min/week) at
      three and 12 months by 74 (95% CI = 45-103) and 30 (95% CI = 3-57), respectively.
      Fidelity: postal and nurse groups showed strong positive associations of diary
      return with steps/day at three months: postal 1458 (95% CI = 854-2061), nurse 873
      (95% CI = 190-1555). MVPA in bouts (min/week): postal 64 (95% CI = 33-94), nurse
      50 (95% CI = 15-85). At 12 months, only the postal group effects remained
      statistically significant: steps/day 1114 (95% CI = 538-1689), MVPA 47 (95% CI =
      18-75). Regular pedometer use in the postal group only was associated with higher
      three-month and 12-month steps/day: 1029 (95% CI = 383-1675) and 606 (95% CI = 22
      1190), respectively, and with MVPA in bouts at three months: 40 (95% CI = 6-73).
      CONCLUSION: Process evaluation measures demonstrated significant associations
      with PA outcomes at three and 12 months. We cannot infer causality, but the
      associations between the process measures and PA outcomes suggest that they were
      important in enabling the trial changes observed and should be considered core
      components of the PACE-UP nurse and postal interventions. We have shown the MRC
      framework to be a useful tool for process evaluation of intervention
      implementation. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN98538934 . Registered
      on 2 March 2012.

PMID- 29357922
TI  - Implementation of health promotion programmes in schools: an approach to
      understand the influence of contextual factors on the process?
AB  - BACKGROUND: Implementing complex and multi-level public health programmes is
      challenging in school settings. Discrepancies between expected and actual
      programme outcomes are often reported. Such discrepancies are due to complex
      interactions between contextual factors. Contextual factors relate to the
      setting, the community, in which implementation occurs, the stakeholders
      involved, and the characteristics of the programme itself. This work uses realist
      evaluation to understand how contextual factors influence the implementation
      process, to result in variable programme outcomes. This study focuses on
      identifying contextual factors, pinpointing combinations of contextual factors,
      and understanding interactions and effects of such factors and combinations on
      programme outcomes on different levels of the implementation process. METHODS:
      Schools which had participated in a school-based health promotion programme
      between 2012 and 2015 were included. Two sets of qualitative data were collected:
      semi-structured interviews with school staff and programme coordinators; and
      written documents about the actions implemented in a selection of four schools.
      Quantitative data included 1553 questionnaires targeting pupils aged 8 to 11 in
      14 schools to describe the different school contexts. RESULTS: The comparison
      between what was expected from the programme (programme theory) and the outcomes
      identified in the field data, showed that some of the mechanisms expected to
      support the implementation of the programme, did not operate as anticipated (e.g.
      inclusion of training, initiation by decision-maker). Key factors which
      influenced the implementation process included, amongst other factors, the mode
      of introduction of the programme, home/school relationship, leadership of the
      management team, and the level of delegated power. Five types of interactions
      between contextual factors were put forward: enabling, hindering, neutral,
      counterbalancing and moderating effects. Recurrent combinations of factors were
      identified. Implementation was more challenging in vulnerable schools where
      school climate was poor. CONCLUSION: A single programme cannot be suited or
      introduced in the same manner in every context. However, key recurrent
      combinations of contextual factors could contribute to the design of
      implementation patterns, which could provide guidelines and recommendation for
      grass-root programme implementation.

PMID- 29357923
TI  - Interleukin-6/interleukin-6 receptor complex promotes osteogenic differentiation
      of bone marrow-derived mesenchymal stem cells.
AB  - BACKGROUND: Interleukin-6 (IL-6) with IL-6 receptor (IL-6R) play an important
      role in the tissue regeneration in vivo, especially bone metabolism. Bone marrow 
      derived mesenchymal stem cells (BM-MSCs) are multipotent stromal cells, which are
      main origin of osteoblasts. However, the roles of IL-6 and IL-6R in the
      osteogenic differentiation of BM-MSCs are still unclear. METHODS: The expression
      of IL-6 and IL-6R was detected in BM-MSCs during osteogenic differentiation. The
      activation of the STAT3 pathway was assessed and its role in the osteogenic
      differentiation of BM-MSCs was determined using the specific inhibitor AG490.
      Exogenous IL-6/soluble IL-6R or antibodies against IL-6/IL-6R were used to
      confirm the mechanism by which the IL-6/IL-6R complex promotes the osteogenic
      differentiation. RESULTS: The levels of IL-6 and IL-6R, especially the level of
      membranous IL-6R but not that of soluble IL-6R, increased during osteogenic
      differentiation in BM-MSCs. The levels of IL-6 and IL-6R were positively
      correlated with the osteogenic potential of BM-MSCs. The STAT3 signaling pathway
      was activated during the osteogenic differentiation of BM-MSCs. AG490 markedly
      inhibited the activation of the STAT3 pathway and, subsequently, the osteogenic
      differentiation potential of BM-MSCs. Additionally, exogenous IL-6 and soluble IL
      6R accelerated the osteogenic differentiation of BM-MSCs. In contrast, antibodies
      against IL-6 or IL-6R suppressed the osteogenic differentiation of BM-MSCs.
      Moreover, IL-6 and IL-6R were found to stimulate each other's expression in BM
      MSCs. CONCLUSIONS: IL-6 and IL-6R levels increase during the osteogenic
      differentiation of BM-MSCs. These two molecules form a complex to activate the
      downstream STAT3 signaling pathway, which promotes osteogenic differentiation in
      BM-MSCs via an autocrine/paracrine feedback loop.

PMID- 29357925
TI  - Intra-amniotic inflammation and child neurodevelopment: a systematic review
      protocol.
AB  - BACKGROUND: Intra-amniotic inflammation is associated with adverse pregnancy and
      neonatal outcomes. However, the impact on child neurodevelopment remains unclear.
      We aim to assess the effect of intra-amniotic inflammation on neurodevelopmental
      outcomes in children. METHODS: The databases MEDLINE, Embase, CINAHL, and
      Cochrane will be searched from their inception until November 2017. Randomized
      trials and cohort studies in which inflammatory markers were measured in amniotic
      fluid collected by amniocentesis and in which infant's neurodevelopment was
      assessed will be eligible. Two reviewers will independently select eligible
      studies, assess their risk of bias, and extract data. Results will be compared
      and a third party will be consulted in case of disagreement. Our primary outcome
      of interest is child neurodevelopment, assessed with either a validated tool or
      by revision of medical records for specific diagnosis. Secondary outcomes will
      include abnormal brain imaging. Relative risks will be pooled and sensitivity
      analyses will be performed for the indication of amniocentesis, gestational age
      at amniocentesis, gestational age at delivery, and fetal sex. Risk of bias will
      be assessed using the Cochrane Collaboration's tool for assessing the risk of
      bias in randomized trials or an adapted version of the ROBINS-1 for the risk of
      bias in non-randomized studies. DISCUSSION: This systematic review will report
      the current evidence regarding the association between amniotic inflammation and
      child neurodevelopment, and the modifiers of this association. The review will
      generate new hypotheses on pathological pathways and will guide future research.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017 65065.

PMID- 29357924
TI  - An automated A-value measurement tool for accurate cochlear duct length
      estimation.
AB  - BACKGROUND: There has been renewed interest in the cochlear duct length (CDL) for
      preoperative cochlear implant electrode selection and postoperative generation of
      patient-specific frequency maps. The CDL can be estimated by measuring the A
      value, which is defined as the length between the round window and the furthest
      point on the basal turn. Unfortunately, there is significant intra- and inter
      observer variability when these measurements are made clinically. The objective
      of this study was to develop an automated A-value measurement algorithm to
      improve accuracy and eliminate observer variability. METHOD: Clinical and micro
      CT images of 20 cadaveric cochleae specimens were acquired. The micro-CT of one
      sample was chosen as the atlas, and A-value fiducials were placed onto that
      image. Image registration (rigid affine and non-rigid B-spline) was applied
      between the atlas and the 19 remaining clinical CT images. The registration
      transform was applied to the A-value fiducials, and the A-value was then
      automatically calculated for each specimen. High resolution micro-CT images of
      the same 19 specimens were used to measure the gold standard A-values for
      comparison against the manual and automated methods. RESULTS: The registration
      algorithm had excellent qualitative overlap between the atlas and target images.
      The automated method eliminated the observer variability and the systematic
      underestimation by experts. Manual measurement of the A-value on clinical CT had
      a mean error of 9.5 +/- 4.3% compared to micro-CT, and this improved to an error
      of 2.7 +/- 2.1% using the automated algorithm. Both the automated and manual
      methods correlated significantly with the gold standard micro-CT A-values (r =
      0.70, p < 0.01 and r = 0.69, p < 0.01, respectively). CONCLUSION: An automated A
      value measurement tool using atlas-based registration methods was successfully
      developed and validated. The automated method eliminated the observer variability
      and improved accuracy as compared to manual measurements by experts. This open
      source tool has the potential to benefit cochlear implant recipients in the
      future.

PMID- 29357926
TI  - Psychotropic medication non-adherence and associated factors among adult patients
      with major psychiatric disorders: a protocol for a systematic review.
AB  - BACKGROUND: Evidence from the global burden of diseases show that psychiatric
      disorders are a growing public health concern. Maintaining adherence to
      medication is the most essential, but challenging course in the pharmacological
      treatment modality for major psychiatric disorders. Nevertheless, there is a
      paucity of abridged evidence on the level of psychotropic medication non
      adherence and associated factors. Therefore, we aim to systematically summarize
      existing primary studies finding to estimate the level and identify associated
      factors of psychotropic medication non-adherence among adult patients with major
      psychiatric disorders. METHODS: We will search studies using computerized search
      engines, main electronic databases and other relevant sources. PubMed (Medline),
      EMBASE, CINAHL, PsycINFO, Web of Science, WHO Global Health Library, and direct
      Google search will be searched to retrieve studies written in English language
      before December 2017. Observational studies (cross-sectional, case-control,
      cohort or longitudinal, survey and surveillance reports) on major psychiatric
      disorders (schizophrenia, major depressive and bipolar disorders) among adult
      patients will be eligible. Data will be extracted independently by two authors.
      Data synthesis and statistical analysis will be carried out. Pooled estimate will
      be done to quantify the level of psychotropic medication non-adherence using
      Comprehensive Meta-Analysis software. DISCUSSION: Psychiatric disorders remain a
      public health, social and economic concern worldwide. Management of major
      psychiatric disorders is highly affected by medication non-adherence. Thus,
      undertaking an integrated and multifaceted approach is necessary to reduce the
      burden of medication non-adherence, and enhance the quality of patients' life.
      Evidence is required to design appropriate intervention to prevent psychotropic
      medication non-adherence. PROTOCOL REGISTRATION: PROSPERO: 2017: CRD42017067436 .

PMID- 29357927
TI  - Targeted reversion of induced pluripotent stem cells from patients with human
      cleidocranial dysplasia improves bone regeneration in a rat calvarial bone defect
      model.
AB  - BACKGROUND: Runt-related transcription factor 2 (RUNX2) haploinsufficiency causes
      cleidocranial dysplasia (CCD) which is characterized by supernumerary teeth,
      short stature, clavicular dysplasia, and osteoporosis. At present, as a
      therapeutic strategy for osteoporosis, mesenchymal stem cell (MSC)
      transplantation therapy is performed in addition to drug therapy. However, MSC
      based therapy for osteoporosis in CCD patients is difficult due to a reduction in
      the ability of MSCs to differentiate into osteoblasts resulting from impaired
      RUNX2 function. Here, we investigated whether induced pluripotent stem cells
      (iPSCs) properly differentiate into osteoblasts after repairing the RUNX2
      mutation in iPSCs derived from CCD patients to establish normal iPSCs, and
      whether engraftment of osteoblasts derived from properly reverted iPSCs results
      in better regeneration in immunodeficient rat calvarial bone defect models.
      METHODS: Two cases of CCD patient-derived induced pluripotent stem cells (CCD
      iPSCs) were generated using retroviral vectors (OCT3/4, SOX2, KLF4, and c-MYC) or
      a Sendai virus SeVdp vector (KOSM302L). Reverted iPSCs were established using
      programmable nucleases, clustered regularly interspaced short palindromic repeats
      (CRISPR)/Cas-derived RNA-guided endonucleases, to correct mutations in CCD-iPSCs.
      The mRNA expressions of osteoblast-specific markers were analyzed using
      quantitative reverse-transcriptase polymerase chain reaction. iPSCs-derived
      osteoblasts were transplanted into rat calvarial bone defects, and bone
      regeneration was evaluated using microcomputed tomography analysis and
      histological analysis. RESULTS: Mutation analysis showed that both contained
      nonsense mutations: one at the very beginning of exon 1 and the other at the
      initial position of the nuclear matrix-targeting signal. The osteoblasts derived
      from CCD-iPSCs (CCD-OBs) expressed low levels of several osteoblast
      differentiation markers, and transplantation of these osteoblasts into calvarial
      bone defects created in rats with severe combined immunodeficiency showed poor
      regeneration. However, reverted iPSCs improved the abnormal osteoblast
      differentiation which resulted in much better engraftment into the rat calvarial
      bone defect. CONCLUSIONS: Taken together, these results demonstrate that patient
      specific iPSC technology can not only provide a useful disease model to elucidate
      the role of RUNX2 in osteoblastic differentiation but also raises the tantalizing
      prospect that reverted iPSCs might provide a practical medical treatment for CCD.

PMID- 29357928
TI  - Evaluation of ex vivo produced endothelial progenitor cells for autologous
      transplantation in primates.
AB  - BACKGROUND: Autologous transplantation of endothelial progenitor cells (EPCs) is
      a promising therapeutic approach in the treatment of various vascular diseases.
      We previously reported a two-step culture system for scalable generation of human
      EPCs derived from cord blood CD34+ cells ex vivo. Here, we now apply this culture
      system to expand and differentiate human and nonhuman primate EPCs from mobilized
      peripheral blood (PB) CD34+ cells for the therapeutic potential of autologous
      transplantation. METHODS: The human and nonhuman primate EPCs from mobilized PB
      CD34+ cells were cultured according to our previously reported system. The
      generated adherent cells were then characterized by the morphology, surface
      markers, nitric oxide (NO)/endothelial NO synthase (eNOS) levels and Dil
      acetylated low-density lipoprotein (Dil-Ac-LDL) uptake/fluorescein isothiocyanate
      (FITC)-lectin binding actives. Furthermore, the efficacy and safety studies were
      performed by autologous transplantation via hepatic portal vein injection in a
      nonhuman primate model with acute liver sinusoidal endothelial cell injury.
      RESULTS: The mobilized PB CD34+ cells from both human and nonhuman primate were
      efficiently expanded and differentiated. Over 2 * 108 adherent cells were
      generated from 20 mL mobilized primate PB (1.51 * 106 +/- 3.39 * 105 CD34+ cells)
      by 36-day culture and more than 80% of the produced cells were identified as
      EPCs/endothelial cells (ECs). In the autologous transplant model, the injected
      EPC/ECs from nonhuman primate PB were scattered in the intercellular spaces of
      hepatocytes at the hepatic tissues 14 days post-transplantation, indicating
      successful migration and reconstitution in the liver structure as the functional
      EPCs/ECs. CONCLUSIONS: We successfully applied our previous two-step culture
      system for the generation of primate EPCs from mobilized PB CD34+ cells,
      evaluated the phenotypes ex vivo, and transplanted autologous EPCs/ECs in a
      nonhuman primate model. Our study indicates that it may be possible for these ex
      vivo high-efficient expanded EPCs to be used in clinical cell therapy.

PMID- 29357930
TI  - What are the barriers and facilitators for third sector organisations (non
      profits) to evaluate their services? A systematic review.
AB  - BACKGROUND: The third sector is becoming a more common provider of social and
      health services, but little is known about how third sector organisations (TSOs)
      evaluate their activities. Past research has reported that the third sector is
      under increasing pressure to evaluate its impact and performance by government
      and other commissioning bodies. However, in responding to this increased pressure
      to undertake evaluation, research suggests that many TSOs struggle to evaluate
      their activities following the principles of evidence-based practice (EBP). Yet,
      there has been no systematic effort to investigate why the third sector is
      struggling to provide good quality evidence of its effects. METHODS: This
      systematic review is reported following the PRISMA guidelines. Ten
      interdisciplinary databases were searched using a search string developed
      following best practice and in consultation with an information systems expert.
      Included studies were primary research of any research design investigating
      barriers to and facilitators of the evaluation process of TSOs as identified by
      practitioners. All studies were quality appraised, and the results were
      synthesised as a thematic summary. RESULTS: Twenty-four studies were included,
      which mainly investigated TSOs working within health and social services. The
      thematic summary identified the main barriers for TSOs to undertake evaluation to
      be related to the (1) lack of financial resources, (2) lack of technical
      capability and evaluation literacy and (3) challenges around identifying relevant
      evaluation systems and outcome indicators. Key facilitating factors involved (1)
      getting the appropriate support, (2) having an organisational culture that
      supports evaluation and (3) the motivation to be accountable to stakeholders.
      These findings were robust to study quality. CONCLUSIONS: This review constitutes
      the first systematic effort to synthesise existing literature on factors
      supporting and preventing evaluation by TSOs. The prevalence of factors revolving
      around the lack of support, resources and clarity on appropriate outcome
      indicators suggests that many of the identified challenges may be met by applying
      evidence-based and stakeholder-inclusive strategies to develop shared evaluation
      requirements. Future efforts should address the application of EBP as part of the
      commissioning process of TSOs.

PMID- 29357929
TI  - Addition of platinum derivatives to neoadjuvant single-agent fluoropyrimidine
      chemoradiotherapy in patients with stage II/III rectal cancer: protocol for a
      systematic review and meta-analysis (PROSPERO CRD42017073064).
AB  - BACKGROUND: Neoadjuvant (chemo-)radiation has proven to improve local control
      compared to surgery alone, but this improvement did not translate into better
      overall or disease-specific survival. The addition of oxaliplatin to
      fluoropyrimidine-based neoadjuvant chemoradiotherapy holds the potential of
      positively affecting survival in this context since it has been proven effective
      in the palliative and adjuvant setting of colorectal cancer. Thus, the objective
      of this systematic review is to assess the efficacy, safety, and quality of life
      resulting from adding a platinum derivative to neoadjuvant single-agent
      fluoropyrimidine-based chemoradiotherapy in patients with Union for International
      Cancer Control stage II and III rectal cancer. METHODS: MEDLINE, Web of Science,
      and Cochrane Central Register of Controlled Trials will be systematically
      searched to identify all randomized controlled trials comparing single-agent
      fluoropyrimidine-based chemoradiotherapy to combined neoadjuvant therapy
      including a platinum derivative. Predefined data on trial design, quality,
      patient characteristics, and endpoints will be extracted. Quality of included
      trials will be assessed according to the Cochrane Risk of Bias Tool, and the
      GRADE recommendations will be applied to judge the quality of the resulting
      evidence. The main outcome parameter will be survival, but also treatment
      toxicity, perioperative morbidity, and quality of life will be assessed.
      DISCUSSION: The findings of this systematic review and meta-analysis will provide
      novel insights into the efficacy and safety of combined neoadjuvant
      chemoradiotherapy including a platinum derivative and may form a basis for future
      clinical decision-making, guideline evaluation, and research prioritization.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017073064.

PMID- 29357931
TI  - Physical activity and the prevention, reduction, and treatment of alcohol and/or
      substance use across the lifespan (The PHASE review): protocol for a systematic
      review.
AB  - BACKGROUND: Alcohol and substance use results in significant human and economic
      cost globally and is associated with economic costs of L21 billion and L15billion
      within the UK, respectively, and trends for use are not improving.
      Pharmacological interventions are well researched, but relapse rates across
      interventions for substance and alcohol use disorders are as high as 60-90%.
      Physical activity may offer an alternative or adjunct approach to reducing rates
      of alcohol and substance use that is associated with few adverse side effects, is
      easily accessible, and is potentially cost-effective. Through psychological,
      behavioural, and physiological mechanisms, physical activity may offer benefits
      in the prevention, reduction, and treatment of alcohol and substance use across
      the lifespan. Whilst physical activity is widely advocated as offering benefit,
      no systematic review exists of physical activity (in all forms) and its effects
      on all levels of alcohol and substance use across all ages to help inform
      policymakers, service providers, and commissioners. METHODS: The objectives of
      this mixed methods systematic review are to describe and evaluate the
      quantitative and qualitative research obtained by a diverse search strategy on
      the impact of physical activity and its potential to: 1. Reduce the risk of
      progression to alcohol and/or substance use (PREVENTION) 2. Support individuals
      to reduce alcohol and/or substance use for harm reduction (REDUCTION), and 3.
      Promote abstinence and relapse prevention during and after treatment for an
      alcohol and/or substance use disorder (TREATMENT). With the input of key
      stakeholders, we aim to assess how what we know can be translated into policy and
      practice. Quantitative, qualitative, service evaluations, and economic analyses
      will be brought together in a final narrative synthesis that will describe the
      potential benefits of physical activity for whom, in what conditions, and in what
      form. DISCUSSION: This review will provide details of what is known about
      physical activity and the prevention, reduction, and treatment of alcohol and/or
      substance use. The synthesised findings will be disseminated to policymakers,
      service providers, and commissioners in the UK. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO number: CRD42017079322 .

PMID- 29357933
TI  - Metabolic flux analysis and the NAD(P)H/NAD(P)+ ratios in chemostat cultures of
      Azotobacter vinelandii.
AB  - BACKGROUND: Azotobacter vinelandii is a bacterium that produces alginate and
      polyhydroxybutyrate (P3HB); however, the role of NAD(P)H/NAD(P)+ ratios on the
      metabolic fluxes through biosynthesis pathways of these biopolymers remains
      unknown. The aim of this study was to evaluate the NAD(P)H/NAD(P) + ratios and
      the metabolic fluxes involved in alginate and P3HB biosynthesis, under oxygen
      limiting and non-limiting oxygen conditions. RESULTS: The results reveal that
      changes in the oxygen availability have an important effect on the metabolic
      fluxes and intracellular NADPH/NADP+ ratio, showing that at the lowest OTR (2.4
      mmol L-1 h-1), the flux through the tricarboxylic acid (TCA) cycle decreased 27.6
      fold, but the flux through the P3HB biosynthesis increased 6.6-fold in contrast
      to the cultures without oxygen limitation (OTR = 14.6 mmol L-1 h-1). This was
      consistent with the increase in the level of transcription of phbB and the P3HB
      biosynthesis. In addition, under conditions without oxygen limitation, there was
      an increase in the carbon uptake rate (twofold), as well as in the flux through
      the pentose phosphate (PP) pathway (4.8-fold), compared to the condition of 2.4
      mmol L-1 h-1. At the highest OTR condition, a decrease in the NADPH/NADP+ ratio
      of threefold was observed, probably as a response to the high respiration rate
      induced by the respiratory protection of the nitrogenase under diazotrophic
      conditions, correlating with a high expression of the uncoupled respiratory chain
      genes (ndhII and cydA) and induction of the expression of the genes encoding the
      nitrogenase complex (nifH). CONCLUSIONS: We have demonstrated that changes in
      oxygen availability affect the internal redox state of the cell and carbon
      metabolic fluxes. This also has a strong impact on the TCA cycle and PP pathway
      as well as on alginate and P3HB biosynthetic fluxes.

PMID- 29357932
TI  - Does hyperthyroidism worsen prognosis of thyroid carcinoma? A retrospective
      analysis on 2820 consecutive thyroidectomies.
AB  - BACKGROUND: Hyperthyroidism is associated with high incidence of thyroid
      carcinoma; furthermore, tumors arisen in hyperthyroid tissue show an aggressive
      behavior. Thyroid Stimulating Hormone (TSH) and Thyroid-stimulating antibodies,
      present in Graves's disease, seem to play a key role in carcinogenesis and
      tumoral growth. METHODS: We retrospectively reviewed our series of patients who
      underwent thyroidectomy for thyroid carcinoma. We compared pathological features
      and surgical outcomes of hyperthyroid versus euthyroid patients. RESULTS: From
      2007 to 2015, 909 thyroidectomies were performed at our institution for thyroid
      cancer: 87 patients were hyperthyroid and 822 euthyroid. We observed, in
      hyperthyroid patients, a higher rate of transient hypoparathyroidism (28.1% vs
      13.2%; p < 0.01) and of node metastases (12.6% vs 6.1%; p = 0.03); also local
      recurrence rate was higher (5.7% vs 2.5%) even if not statistically significant
      (p = 0.17). Five-year disease free survival rate was significant lower in the
      same group (89.1% vs 96.6%; p = 0.03). CONCLUSION: Thyroid cancers in
      hyperthyroid patients have an aggressive behavior, with high incidence of local
      invasion and a worse prognosis than euthyroid patients. All hyperthyroid patients
      should undergo a careful evaluation with ultrasound and scintigraphy; in case of
      suspicious nodules, an aggressive approach, including thyroidectomy and
      lymphectomy, is justified. In patients with toxic adenoma, thyroid cancer is
      uncommon, thus a loboisthmectomy can be safely performed. TRIAL REGISTRATION
      NUMBER: Research registry n. 2670 registered 19 June 2017 (retrospectively
      registered).

PMID- 29357934
TI  - The importance of genotype-phenotype correlation in the clinical management of
      Marfan syndrome.
AB  - BACKGROUND: Marfan syndrome (MFS) is a disorder of autosomal dominant
      inheritance, in which aortic root dilation is the main cause of morbidity and
      mortality. Fibrillin-1 (FBN-1) gene mutations are found in more than 90% of MFS
      cases. The aim of our study was to summarise variants in FBN-1 and establish the
      genotype-phenotype correlation, with particular interest in the onset of aortic
      events, in a broad population of patients with an initial clinical suspicion of
      MFS. MATERIAL AND METHODS: This single centre prospective cohort study included
      all patients presenting variants in the FBN-1 gene who visited a Hereditary
      Aortopathy clinic between September 2010 and October 2016. RESULTS: The study
      included 90 patients with FBN-1 variants corresponding to 58 non-interrelated
      families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been
      described, 23 of which had been identified as associated with MFS, while the the
      remainder are described for the first time. For 84 patients (93.3%), it was
      possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent
      criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic
      event (with either prophylactic surgery for aneurysm or dissection), whereas 20
      of the 35 patients with truncating mutations had suffered an event (13.6% vs.
      57.1%, p < 0.001). These events tended to occur at earlier ages in patients with
      truncating compared to those with missense mutations, although not significantly
      (41.33 +/- 3.77 vs. 37.5 +/- 9.62 years, p = 0.162). CONCLUSIONS: Patients with
      MFS and truncating variants in FBN-1 presented a higher proportion of aortic
      events, compared to a more benign course in patients with missense mutations.
      Genetic findings could, therefore, have importance not only in the diagnosis, but
      also in risk stratification and clinical management of patients with suspected
      MFS.

PMID- 29357935
TI  - Temporary carriage of bovine coronavirus and bovine respiratory syncytial virus
      by fomites and human nasal mucosa after exposure to infected calves.
AB  - BACKGROUND: In order to prevent spread of the endemic pathogens bovine
      coronavirus (BCoV) and bovine respiratory syncytial virus (BRSV) between herds,
      knowledge of indirect transmission by personnel and fomites is fundamental. The
      aims of the study were to determine the duration of viral RNA carriage and the
      infectivity of viral particles on fomites and human nasal mucosa after exposure
      to BCoV and BRSV. During two animal infection experiments, swabs were collected
      from personnel (nasal mucosa) and their clothes, boots and equipment after
      contact with calves shedding either virus. Viral RNA was quantified by RT-qPCR or
      droplet digital RT-PCR (RT-ddPCR), and selected samples with high levels of viral
      RNA were tested by cell culture for infectivity. RESULTS: For BCoV, 46% (n = 80)
      of the swabs from human nasal mucosa collected 30 min after exposure were
      positive by RT-qPCR. After two, four and six hours, 15%, 5% and 0% of the swabs
      were positive, respectively. Infective virions were not detected in mucosal swabs
      (n = 2). A high viral RNA load was detected on 97% (n = 44) of the fomites 24 h
      after exposure, and infective virions were detected in two of three swabs. For
      BRSV, 35% (n = 26) of the human nasal mucosa swabs collected 30 min after
      exposure, were positive by RT-ddPCR, but none were positive for infective
      virions. Of the fomites, 89% (n = 38) were positive for BRSV RNA 24 h after
      exposure, but all were negative for infective viruses. CONCLUSIONS: The results
      indicate that human nasal mucosa can carry both BCoV and BRSV RNA after exposure
      to virus shedding calves, but the carriage seems short-lived and the transmission
      potential is likely limited. High viral loads on contaminates fomites 24 h after
      exposure to infected animals, and detection of infective BCoV, indicate that
      contaminated fomites represent a significant risk for indirect transmission
      between herds.

PMID- 29357936
TI  - The effect of metabolic stress on genome stability of a synthetic biology chassis
      Escherichia coli K12 strain.
AB  - BACKGROUND: Synthetic organism-based biotechnologies are increasingly being
      proposed for environmental applications, such as in situ sensing. Typically, the
      novel function of these organisms is delivered by compiling genetic fragments in
      the genome of a chassis organism. To behave predictably, these chassis are
      designed with reduced genomes that minimize biological complexity. However, in
      these proposed applications it is expected that even when contained within a
      device, organisms will be exposed to fluctuating, often stressful, conditions and
      it is not clear whether their genomes will retain stability. RESULTS: Here we
      employed a chemostat design which enabled us to maintained two strains of E. coli
      K12 under sustained starvation stress: first the reduced genome synthetic biology
      chassis MDS42 and then, the control parent strain MG1655. We estimated mutation
      rates and utilised them as indicators of an increase in genome instability. We
      show that within 24 h the spontaneous mutation rate had increased similarly in
      both strains, destabilizing the genomes. High rates were maintained for the
      duration of the experiment. Growth rates of a cohort of randomly sampled mutants
      from both strains were utilized as a proxy for emerging phenotypic, and by
      association genetic variation. Mutant growth rates were consistently less than
      rates in non-mutants, an indicator of reduced fitness and the presence of mildly
      deleterious mutations in both the strains. In addition, the effect of these
      mutations on the populations as a whole varied by strain. CONCLUSIONS: Overall,
      this study shows that genome reductions in the MDS42 did not stabilize the
      chassis under metabolic stress. Over time, this could compromise the
      effectiveness of synthetic organisms built on chassis in environmental
      applications.

PMID- 29357937
TI  - Surgical strategies protecting against right ventricular dilatation following
      tetralogy of Fallot repair.
AB  - BACKGROUND: Right ventricular (RV) volume overload increases morbidity and
      mortality after tetralogy of Fallot (TOF) repair. Surgical strategies like
      pulmonary leaflets sparing and tricuspid valve repair at time of primary repair
      may decrease RV overload. Our objective is to evaluate early and midterm results
      of pulmonary leaflets sparing with infundibular preservation and tricuspid valve
      repair in selected TOF patients with moderate pulmonary annular hypoplasia.
      METHODS: From 2011 to 2016; 46 patients with TOF and moderate pulmonary annular
      hypoplasia had surgical repair with sparing of the pulmonary valve leaflets.
      Concomitant tricuspid valve repair was performed in 33 patients (71.8%). Mean age
      was 13.1 +/- 4.8 months, 68% were males (n = 31) and mean weight was 9.5 +/- 2.3
      kg. Preoperative McGoon ratio was 1.9 +/- 0.4 and pulmonary valve z-score ranges
      from - 2 to - 3. Preoperative pressure gradient of RVOT was 80.9 +/- 7.7 mmHg and
      10.9% had minor coronary anomalies (n = 5). RESULTS: All repairs were performed
      through trans-atrial trans-pulmonary approach. 87% had pulmonary valve
      commissurotomy (n = 40). Mean cardiopulmonary bypass time was 71 +/- 6.3 min and
      ischemic time 42.4 +/- 4.9 min. Hospital mortality occurred in 4.3% (n = 2). Mean
      RVOT pressure gradient decreased significantly postoperatively (28.8 +/- 7.2
      mmHg, p-value< .001) and at the last follow up (23.6 +/- 1.8 mmHg, p-value<
      .001). Pulmonary regurgitation progressed by one grade in 2 patients compared to
      the postoperative grade. 1 patient (2.5%) had late mortality and reintervention
      was required in 5 patients (12.5%). CONCLUSION: Pulmonary leaflets sparing, and
      tricuspid valve repair are safe for TOF repair with no added morbidity or
      mortality. These procedures could contribute to reducing right ventricular volume
      overload over time after TOF repair.

PMID- 29357938
TI  - Integration analysis of microRNA and mRNA paired expression profiling identifies
      deregulated microRNA-transcription factor-gene regulatory networks in ovarian
      endometriosis.
AB  - BACKGROUND: The etiology and pathophysiology of endometriosis remain unclear.
      Accumulating evidence suggests that aberrant microRNA (miRNA) and transcription
      factor (TF) expression may be involved in the pathogenesis and development of
      endometriosis. This study therefore aims to survey the key miRNAs, TFs and genes
      and further understand the mechanism of endometriosis. METHODS: Paired expression
      profiling of miRNA and mRNA in ectopic endometria compared with eutopic
      endometria were determined by high-throughput sequencing techniques in eight
      patients with ovarian endometriosis. Binary interactions and circuits among the
      miRNAs, TFs, and corresponding genes were identified by the Pearson correlation
      coefficients. miRNA-TF-gene regulatory networks were constructed using
      bioinformatic methods. Eleven selected miRNAs and TFs were validated by
      quantitative reverse transcription-polymerase chain reaction in 22 patients.
      RESULTS: Overall, 107 differentially expressed miRNAs and 6112 differentially
      expressed mRNAs were identified by comparing the sequencing of the ectopic
      endometrium group and the eutopic endometrium group. The miRNA-TF-gene regulatory
      network consists of 22 miRNAs, 12 TFs and 430 corresponding genes. Specifically,
      some key regulators from the miR-449 and miR-34b/c cluster, miR-200 family, miR
      106a-363 cluster, miR-182/183, FOX family, GATA family, and E2F family as well as
      CEBPA, SOX9 and HNF4A were suggested to play vital regulatory roles in the
      pathogenesis of endometriosis. CONCLUSION: Integration analysis of the miRNA and
      mRNA expression profiles presents a unique insight into the regulatory network of
      this enigmatic disorder and possibly provides clues regarding replacement therapy
      for endometriosis.

PMID- 29357939
TI  - Inherited thrombotic thrombocytopenic purpura mimicking immune thrombocytopenic
      purpura during pregnancy: a case report.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura is a very rare hereditary blood
      deficiency disorder of ADAMTS13 (von Willebrand factor-cleaving protease) and a
      life-threatening thrombotic microangiopathy characterized by thrombocytopenia and
      microangiopathic hemolytic anemia. The deficiency in ADAMTS13 metalloprotease,
      which cleaves the von Willebrand factor, may be congenital or acquired. The
      congenital form is caused by inherited mutations in the ADAMTS13 gene. The
      diagnosis is challenging due to the nonspecific signs and symptoms, as well as
      the rarity of the disease. CASE PRESENTATION: We present an unusual case of a 20
      year-old feoderm woman from northeast region of Brazil who manifested
      thrombocytopenia during her pregnancy which was believed to be immune
      thrombocytopenic purpura. CONCLUSIONS: Considering the importance of a
      differential diagnosis of thrombotic microangiopathic disorders, congenital
      thrombotic thrombocytopenic purpura may mimic the signs and symptoms of pre
      eclampsia/eclampsia, hemolysis with elevated liver enzymes and low platelet count
      syndrome, and atypical hemolytic-uremic syndrome. It should be considered in
      suspect cases in patients with an ADAMTS13 activity at 5% without ADAMTS13
      antibodies.

PMID- 29357940
TI  - Children's experiences and responses towards an intervention for psychological
      preparation for radiotherapy.
AB  - BACKGROUND: Children can experience distress when undergoing radiotherapy as a
      reaction to being scared of and unfamiliar with the procedure. The aim was to
      evaluate children's experiences and responses towards an intervention for
      psychological preparation for radiotherapy. METHODS: A case control design with
      qualitative content analysis of semi-structured interviews and statistical
      analysis of anxiety ratings were used for evaluating a strategy for psychological
      preparation and distraction. Fifty-seven children aged 2 to 18 years and their
      parents participated - 30 children in the baseline group and 27 in the
      intervention group. Child interviews were performed and the child and their
      parents rated the child's anxiety. RESULTS: The intervention was most appropriate
      for the younger children, who enjoyed the digital story, the stuffed animal and
      training with their parents. There were some technical problems and the digital
      story was not detailed enough to fit exactly with various cancer diagnoses.
      Children described suggestions for improvement of the intervention. The ratings
      of the child's anxiety during radiation treatment showed no differences between
      the baseline group and the intervention group. CONCLUSIONS: The children of all
      the age groups experienced their interventions as positive. The strength of the
      intervention was that it encouraged interaction within the family and provided an
      opportunity for siblings and peers to take part in what the child was going
      through. Future research on children's experiences to interventions should be
      encouraged. The intervention and the technical solutions could improve by further
      development. TRIAL REGISTRATION: The study design was structured as an un-matched
      case-control study, baseline group vs. intervention group. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02993978 , Protocol Record 2012-113-31 M. Retrospectively
      registered - 21 November 2016.

PMID- 29357941
TI  - Primary hemophagocytic lymphohistiocytosis in adults: the utility of family
      surveys in a single-center study from China.
AB  - BACKGROUND: This study investigated the clinical characteristics of primary
      hemophagocytic lymphohistiocytosis (HLH) in adults, including immunological
      markers, pedigree findings, and conditions of allogeneic hematopoietic stem cell
      transplantation (Allo-HSCT). METHODS: The study included clinical data of 18
      adult patients with primary HLH treated in our center from June 2010 to January
      2017. RESULTS: Of these 18 cases, pathogenic variants were found in the following
      genes: PRF1 (n = 11), UNC13D (n = 5), SH2D1A (n = 2), RAB27a (n = 1), and LYST (n
      = 2). One patient had pathogenic variants in both PRF1 and UNC13D genes, one
      patient had pathogenic variants in both LYST and UNC13D genes and another patient
      had pathogenic variants in both PRF1 and SH2D1A genes. Additionally, 3 of the 18
      cases involved homozygous pathogenic variants, while 2 cases involved hemizygous
      pathogenic variants. The remaining 13 cases involved compound heterozygous
      pathogenic variants. The natural killer (NK) cell activity test was conducted in
      all 18 cases where 14(77.8%)patients showed reduction in NK cell activity.
      Furthermore, this article presents 3 representative results of the pedigree
      findings from 12 patients who underwent family surveys. The 8 patients who
      underwent Allo-HSCT had a median survival of 27.2 months, as compared with the
      median survival of 7 months for the10 patients who did not undergo Allo-HSCT, a
      significant difference between the two groups of patients (p = 0.006).
      CONCLUSION: PRF1 was one of the most commonly mutated gene in adult patients with
      primary HLH. Family surveys and immunological markers were important for the HLH
      diagnosis and the selection of an appropriate donor. Allo-HSCT was an effective
      therapy for adult primary HLH.

PMID- 29357942
TI  - Contrasting development of lysigenous aerenchyma in two rice genotypes under
      phosphorus deficiency.
AB  - OBJECTIVES: Phosphorus (P) deficiency is a major limitation to plant growth.
      Under several abiotic stresses, including P deficiency, upland cereal crops, such
      as maize, are well known to develop lysigenous aerenchyma, a root tissue
      containing gas spaces. Contrary to upland species, rice develops aerenchyma
      constitutively. Nevertheless, aerenchyma in rice is also enhanced by several
      abiotic stresses, including P deficiency. However, studies are limited and
      genotypic differences are not clear. RESULTS: The formation of inducible
      aerenchyma in response to P deficiency was evaluated in two rice genotypes, DJ123
      and Nerica4. Whole root porosity increased for both genotypes in low P
      conditions, but was more pronounced in DJ123. Direct aerenchyma measurements, at
      20 and 30 mm from the seminal root tip, revealed that aerenchyma in low P
      conditions was only enhanced in DJ123. These results confirm that P deficiency in
      rice induces the formation of aerenchyma, and further show that genotypic
      differences exist. Interestingly, DJ123 is considered tolerant to P deficiency,
      whereas Nerica4 is sensitive, pointing towards a potential role of aerenchyma in
      tolerance to P deficiency.

PMID- 29357943
TI  - MOVING: Motivation-Oriented interVention study for the elderly IN Greifswald:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Cardiovascular diseases (CVD) are the leading cause of mortality. In
      2014, they were responsible for 38.9% of all causes of death in Germany. One
      major risk factor for CVD is a lack of physical activity (PA). A health-promoting
      lifestyle including regular PA and minimizing sitting time (ST) in daily life is
      a central preventive measure. Previous studies have shown that PA decreases in
      older age; 2.4-29% of the people aged over 60 years achieve the World Health
      Organization recommendations. This age group spends on average 9.4 h per day in
      sedentary activities. To increase PA and decrease ST, a low-threshold
      intervention, consisting of individualized feedback letters based on objectively
      measured data of PA and ST, was developed. The research question is: Do
      individual feedback letters, based on accelerometer data, have a positive effect
      on PA and ST? METHODS/DESIGN: MOVING is a two-arm, randomized controlled trial.
      Inclusion criteria are age >= 65 years and the ability to be physically active.
      Exclusion criteria are the permanent use of a wheelchair and simultaneous
      participation in another study on PA. At baseline participants who give informed
      consent will receive general information and recommendations about the positive
      effects of regular PA and less ST. Participants of both groups will receive an
      accelerometer device, which records PA and ST over a period of seven consecutive
      days following by a randomization. Participants in the intervention group will
      receive automatically generated, individualized feedback letters by mail based on
      their PA and ST at baseline and at 3-month follow-up. Further follow-up
      examinations will be carried out at 6 and 12 months. The primary outcome is the
      increase of PA and the reduction of ST after 6 months in the intervention group
      compared to the control group. DISCUSSION: The goal of the study is to examine
      the effects of a simple feedback intervention on PA and ST in elderly people. We
      aim to achieve an effect of 20% increase in moderate-to-vigorous physical
      activity (MVPA). The intervention may have the potential to decrease crucial
      cardiovascular risk factors and, therefore, contribute to prevention of CVD.
      TRIAL REGISTRATION: German Clinical Trials Register, ID: DRKS00010410 .
      Registered on 17 May 2017.

PMID- 29357944
TI  - Minimum values for midluteal plasma progesterone and estradiol concentrations in
      patients who achieved pregnancy with timed intercourse or intrauterine
      insemination without a human menopausal gonadotropin.
AB  - OBJECTIVE: The aim of the study was to assess the lower limits of midluteal
      plasma progesterone and estradiol concentrations in patients who achieved
      pregnancy with timed intercourse or intrauterine insemination without a human
      menopausal gonadotropin stimulation. RESULTS: We included 297 pregnant cycles of
      297 women and assessed midluteal plasma progesterone and estradiol concentrations
      and pregnancy outcomes, retrospectively. These cycles were compared with the non
      pregnant cycles (406 cycles) of the same women who became pregnant. Mean
      midluteal plasma P4 and E2 concentrations were significantly (P < 0.01) higher in
      pregnant cycles (14.5 and 188.5 pg/mL) than in non-pregnant cycles (10.7 and
      162.6 pg/mL). The 5 percentiles of progesterone and estradiol in pregnant cycles
      were 5.6 and 70.2 pg/mL, respectively. The lowest progesterone and estradiol
      levels in pregnant cycles were 2.3 and 23.4 pg/mL, respectively. In non-pregnant
      cycles, many women had low P4 levels that were less than 5.6 ng/mL. Subgroup
      analyses showed slight differences among the four groups, which may have been due
      to the ovarian function of each group. Miscarriage was not related to
      progesterone and estradiol concentrations. These values may be useful for the
      evaluation of necessary values for pregnancy with timed intercourse or
      intrauterine insemination.

PMID- 29357945
TI  - Human stem cells express pannexins.
AB  - OBJECTIVE: Pannexins are channel proteins important for the release of calcium
      and adenosine triphosphate, which are among other functions involved in early
      development. Here, the expression of pannexins was investigated in induced
      pluripotent stem cells derived from human cord blood endothelial cells (hCBiPS2),
      in hematopoietic stem cell-derived induced pluripotent stem cells (HSC_F1285_T
      iPS2) and in human embryonic stem cells (HES-3). The expression of pannexin
      (Panx) 1-3 mRNAs was analyzed in all three undifferentiated stem cell lines. Stem
      cells then underwent undirected differentiation into embryoid bodies and were
      analyzed regarding expression of germ layer-specific genes. RESULTS: Panx1,
      Panx2, and Panx3 mRNAs were expressed in all undifferentiated stem cell lines
      investigated. In comparison, Panx1 showed the highest expression among all
      pannexins. The undirected differentiation resulted in a mixed germ layer genotype
      in all three stem cell lines. Whereas the expression of Panx1 was not affected by
      differentiation, the expression of Panx2 was slightly increased in differentiated
      hCBiPS2 cells, HSC_F1285_T-iPS2 as well as HES3 cells as compared to their
      undifferentiated counterparts. A slight increase of Panx3 expression was observed
      in differentiated hCBiPS2 cells only. In conclusion, pluripotent stem cells
      express all three pannexin genes.

PMID- 29357946
TI  - Follistatin-like protein 1 plays a tumor suppressor role in clear-cell renal cell
      carcinoma.
AB  - BACKGROUND: We previously showed that the expression of follistatin-like protein
      1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell
      carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in
      the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell
      cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene
      expression microarray assays were performed to identify the major signaling
      pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its
      effect on postoperative prognosis were estimated in a cohort with 89 patients.
      RESULTS: FSTL1 knockdown promoted anchorage-independent growth, migration,
      invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression
      attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-kappaB (NF
      kappaB) and hypoxia-inducible factor (HIF) signaling pathways, increased
      epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and
      promoted tumor necrosis factor-alpha-induced degradation of NF-kappaB inhibitor
      (IkappaBalpha) in ccRCC cell lines. FSTL1 immunostaining was selectively positive
      in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was
      significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001).
      The multivariate Cox regression analysis showed that the intratumoral FSTL1
      expression conferred a favorable independent prognosis with a hazard ratio of
      0.325 (95% confidence interval 0.118-0.894). HIF-2alpha expression was negatively
      correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044).
      Intratumoral expression of HIF-2alpha, rather than HIF-1alpha, significantly
      predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS:
      FSTL1 plays a tumor suppression role possibly via repressing the NF-kappaB and
      HIF-2alpha signaling pathways. To increase FSTL1 expression might be a candidate
      therapeutic strategy for metastatic ccRCC.

PMID- 29357950
TI  - Statement on Minimum Standards for the Care of Older People in Emergency
      Departments by the Geriatric Emergency Medicine Special Interest Group of the
      International Federation for Emergency Medicine.

PMID- 29357951
TI  - Maternal and neonatal micronutrient levels in newborns with CHD.
AB  - OBJECTIVE: It is suggested that folic acid and/or multivitamins, taken
      periconceptionally, have a role in the prevention of many congenital anomalies.
      The aim of this study was to determine the serum micronutrient levels in mother
      infant pairs with CHD compared with those with healthy newborns and their
      mothers. METHODS: Serum levels of folic acid, homocysteine, zinc, vitamin A,
      vitamin D, and vitamin B12 were measured from 108 newborns with CHD (study group)
      and 103 healthy newborns (control group). The mothers' micronutrient levels were
      also measured simultaneously. RESULTS: When compared with healthy newborns, for
      both maternal and neonatal data, homocysteine and zinc levels were higher and
      vitamin D levels were lower in the study group. In multivariate analysis, only
      maternal high zinc levels were associated with CHD in the newborns (p=0.02, OR:
      0.9, 95% CI 0.8-0.9). The results did not change when analysed for truncal
      anomalies including truncus arteriosus, tetralogy of Fallot, and d-transposition
      of great arteries. There were positive correlations between maternal and neonatal
      levels of micronutrients, except vitamin B12. CONCLUSION: We thought that high
      homocysteine and zinc levels and low vitamin D levels in mother-infant pairs
      might have a role in the aetiopathogenesis of CHD. Large-scale, prospective
      studies are needed to clarify the role of micronutrients in CHDs.

PMID- 29357952
TI  - Parental influences on children's food behaviours: challenges and opportunities
      from studying culturally diverse samples.

PMID- 29357948
TI  - Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a
      comprehensive review of registration trials and future considerations.
AB  - Early preclinical evidence provided the rationale for programmed cell death 1 (PD
      1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer
      immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a
      mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early
      phase studies investigating several humanized monoclonal IgG4 antibodies
      targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development
      of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food
      and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this
      class is rapidly enlarging with indications for treatment spanning across a
      spectrum of malignancies. The purpose of this review is to highlight the clinical
      development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In
      particular, we focus on detailing the registration trials that have led to FDA
      approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the
      number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers,
      mechanisms of resistance, hyperprogressors, treatment duration and treatment
      beyond progression, immune-related toxicities, and clinical trial design are key
      concepts in need of further consideration to optimize the anticancer potential of
      this class of immunotherapy.

PMID- 29357949
TI  - The 150 most important questions in cancer research and clinical oncology series:
      questions 86-93 : Edited by Chinese Journal of Cancer.
AB  - Since the beginning of 2017, Chinese Journal of Cancer has published a series of
      important questions in cancer research and clinical oncology, which spark diverse
      thoughts, interesting communications, and potential collaborations among
      researchers all over the world. In this article, 8 more questions are presented
      as follows. Question 86. In which circumstances is good supportive care
      associated with a survival advantage in patients with cancer? Question 87. Can we
      develop animal models to mimic immunotherapy response of cancer patients?
      Question 88. What are the mechanisms underlying hepatitis B virus-associated non
      hepatocellular cancers? Question 89. Can we more precisely target tumor
      metabolism by identifying individual patients who would benefit from the
      treatment? Question 90. What type of cranial irradiation-based prophylactic
      therapy combination can dramatically improve the survival of patients with
      extensive small-cell lung cancer? Question 91. How can postoperative radiotherapy
      prolong overall survival of the patients with resected pIIIA-N2 non-small cell
      lung cancer? Question 92. What are the key molecular events that drive oral
      leukoplakia or erythroplakia into oral cancer? Question 93. How could we track
      the chemotherapeutics-driven evolution of tumor genome in non-small cell lung
      cancer for more effective treatment?

PMID- 29357947
TI  - Overnight auto-adjusting continuous airway pressure + standard care compared with
      standard care alone in the prevention of morbidity in sickle cell disease phase
      II (POMS2b): study protocol for a randomised controlled trial.
AB  - BACKGROUND: In addition to pain, sickle cell anaemia (HbSS) complications include
      neurocognitive difficulties in attention and processing speed associated with low
      daytime and night-time oxygen saturation compounded by obstructive sleep apnoea
      (OSA). In the general population OSA is treated with continuous positive airways
      pressure (CPAP). The aim of this single-blind, randomised, controlled phase II
      trial is to compare auto-adjusting CPAP (APAP) with standard care to standard
      care alone in individuals with HbSS to determine whether the intervention
      improves attention and processing speed, brain structure, pain and quality of
      life. METHODS/DESIGN: Eligibility criteria include: ability to provide informed
      consent; age > 8 years; diagnosis of HbSS; and mean overnight saturation of < 90%
      for < 30% of the night (i.e. not meeting current criteria for overnight oxygen
      therapy). Key exclusion criteria are: overnight respiratory support; respiratory
      or decompensated cardiac failure; chronic transfusion; or contraindications to
      APAP therapy or magnetic resonance imaging (MRI). Sixty individuals with HbSS (30
      children and 30 adults) will be randomised to standard care + APAP or standard
      care alone for six months. Minimisation factors are: age group (8-11, 12-15, 16
      22 and > 23 years); silent infarction on MRI; minimum overnight oxygen saturation
      > 90% or < 90%; and hydroxyurea use. For APAP individuals, the intervention is
      administered at home. Adherence and effectiveness are recorded using software
      documenting hours of use each night and overnight oximetry. Participant support
      in terms of appropriate facemask and facilitating adherence are provided by an
      unblinded sleep physiologist. The primary outcome is change in the cancellation
      subtest from the Wechsler scales. Secondary outcomes include general cognitive
      functioning, quantitative brain MRI, blood and urine chemistry, quality of life
      and daily pain via a smartphone App (GoMedSolutions, Inc) and, where possible MRI
      heart, echocardiography, and 6-min walk. These outcomes will be assessed at
      baseline and after six months of treatment by assessors blind to treatment
      assignment. DISCUSSION: Altering oxygen saturation in HbSS may lead to bone
      marrow suppression. This risk will be reduced by monitoring full blood counts at
      baseline, two weeks, three months and six months, providing treatment as
      appropriate and reporting as safety events. TRIAL REGISTRATION: ISRCTN46012373 .
      Registered on 10 July 2015. Protocol Version: 6.0 Date: 24th December 2015
      Sponsor: University Hospital Southampton. Sponsor's protocol code: RHMCHIOT53.

PMID- 29357953
TI  - Perirectal Screening for Carbapenem-Resistant Enterobacteriaceae Obtained From
      100 Consecutive Healthy Pregnant Women in Labor at a Brooklyn Hospital: Results
      and Risk Factors.

PMID- 29357954
TI  - Projecting shortages and surpluses of doctors and nurses in the OECD: what looms
      ahead.
AB  - There is little debate that the health workforce is a key component of the health
      care system. Since the training of doctors and nurses takes several years, and
      the building of new schools even longer, projections are needed to allow for the
      development of health workforce policies. Our work develops a projection model
      for the demand of doctors and nurses by Organisation for Economic Co-operation
      and Development (OECD) countries in the year 2030. The model is based on a
      country's demand for health services, which includes the following factors: per
      capita income, out-of-pocket health expenditures and the ageing of its
      population. The supply of doctors and nurses is projected using country-specific
      autoregressive integrated moving average models. Our work shows how dramatic
      imbalances in the number of doctors and nurses will be in OECD countries should
      current trends continue. For each country in the OECD with sufficient data, we
      report its demand, supply and shortage or surplus of doctors and nurses for 2030.
      We project a shortage of nearly 400,000 doctors across 32 OECD countries and
      shortage of nearly 2.5 million nurses across 23 OECD countries in 2030. We
      discuss the results and suggest policies that address the shortages.

PMID- 29357955
TI  - Demographics of a large paediatric Postural Orthostatic Tachycardia Syndrome
      Program.
AB  - OBJECTIVE: The aim of this study was to identify and evaluate demographic and
      clinical features of paediatric patients with postural orthostatic tachycardia
      syndrome in a tertiary hospital speciality clinic. METHOD: This is a
      retrospective review of clinical data obtained during initial outpatient
      evaluation. RESULTS: A total of 708 patients met the evaluation criteria. Female
      patients outnumbered males, 3.45:1. Caucasians were over-represented at 94.1% of
      patients. Median age at diagnosis was 15.7 years. Joint hypermobility occurred in
      57.3% of patients; 22.4% had hypermobile Ehlers-Danlos syndrome; and 34.9% had
      hypermobility spectrum disorder. Median age of onset of symptoms was 12.6 years
      in patients with hypermobility versus 13.7 years in those without (p=0.0001).
      Median duration of symptoms was 3.3 years with hypermobility versus 1.5 years
      without (p<0.00001). Putative triggers included infection in 23.6% of patients,
      concussion in 11.4%, and surgery/trauma in 2.8%. Concurrent inflammatory
      disorders were noted in 5.2% of patients. Six symptoms comprised 80% of initial
      patient complaints. Overall, 66% of patients subsequently had at least 10
      symptoms, 50% had at least 14 symptoms, and 30% reported at least 26 symptoms.
      Symptoms were largely cardiovascular, gastrointestinal, and neurological.
      Paediatric patients with postural orthostatic tachycardia syndrome seen in a
      large speciality clinic are predominantly female, are mostly Caucasian, have
      onset of symptoms in early adolescence, and have symptoms for over two years
      before diagnosis. Over half of patients have joint hypermobility. More than one
      third of patients have a possible autoimmune or inflammatory trigger, including
      infection, concussion, or surgery/trauma. Patients experience symptoms that are
      highly variable and multi-system in origin over the course of illness.

PMID- 29357956
TI  - Prevalence and risk factors associated with non-attendance in neurodevelopmental
      follow-up clinic among infants with CHD.
AB  - BACKGROUND: Neurodevelopmental impairment is increasingly recognised as a
      potentially disabling outcome of CHD and formal evaluation is recommended for
      high-risk patients. However, data are lacking regarding the proportion of
      eligible children who actually receive neurodevelopmental evaluation, and
      barriers to follow-up are unclear. We examined the prevalence and risk factors
      associated with failure to attend neurodevelopmental follow-up clinic after
      infant cardiac surgery. METHODS: Survivors of infant (<1 year) cardiac surgery at
      our institution (4/2011-3/2014) were included. Socio-demographic and clinical
      characteristics were evaluated in neurodevelopmental clinic attendees and non
      attendees in univariate and multivariable analyses. RESULTS: A total of 552
      patients were included; median age at surgery was 2.4 months, 15% were premature,
      and 80% had moderate-severe CHD. Only 17% returned for neurodevelopmental
      evaluation, with a median age of 12.4 months. In univariate analysis, non
      attendees were older at surgery, had lower surgical complexity, fewer non-cardiac
      anomalies, shorter hospital stay, and lived farther from the surgical center. Non
      attendee families had lower income, and fewer were college graduates or had
      private insurance. In multivariable analysis, lack of private insurance remained
      independently associated with non-attendance (adjusted odds ratio 1.85, p=0.01),
      with a trend towards significance for distance from surgical center (adjusted
      odds ratio 2.86, p=0.054 for ?200 miles). CONCLUSIONS: The majority of infants
      with CHD at high risk for neurodevelopmental dysfunction evaluated in this study
      are not receiving important neurodevelopmental evaluation. Efforts to remove
      financial/insurance barriers, increase access to neurodevelopmental clinics, and
      better delineate other barriers to receipt of neurodevelopmental evaluation are
      needed.

PMID- 29357957
TI  - Double sequential cardioversion for refractory ventricular tachycardia: A case
      report.
AB  - ABSTRACTSustained monomorphic ventricular tachycardia (VT) can result in
      hypoperfusion or devolve into more dangerous rhythms such as ventricular
      fibrillation. In an unstable patient with VT and a pulse, synchronized
      cardioversion is the first-line treatment. When the VT is refractory to standard
      cardioversion, the next step is to add an antiarrhythmic, such as amiodarone,
      that carries with it the risk of lowering blood pressure in the already
      hypotensive patient. Here we describe a case of double sequential synchronized
      cardioversion of a patient with unstable VT refractory to standard direct current
      cardioversion, resulting in a rapid conversion to sinus rhythm and return to
      hemodynamic stability. The benefit of this technique is that it may obviate the
      need for rapid infusion of medications, such as amiodarone, in the acute setting
      that may worsen hypotension in the already unstable patient.

PMID- 29357958
TI  - Sex- and age patterns in incidence of infectious diseases in Germany: analyses of
      surveillance records over a 13-year period (2001-2013).
AB  - Sex differences in the incidence of infections may indicate different risk
      factors and behaviour but have not been analysed across pathogens. Based on 3.96
      million records of 33 pathogens in Germany, notified from 2001 to 2013, we
      applied Poisson regression to generate age-standardised incidence rate ratios and
      assessed their distribution across age and sex. The following trends became
      apparent: (a) pathogens with male incidence preponderance at infant and child age
      (meningococcal disease (incidence rate ratio (IRR) = 1.19, 95% CI 1.03-1.38, age
      = 0-4); influenza (IRR = 1.09, 95% CI 1.06-1.13, age = 0-4)), (b) pathogens with
      sex-switch in incidence preponderance at puberty (e.g. norovirus (IRR = 1.10, 95%
      CI 1.02-1.19 in age = 5-14, IRR = 0.96, 95% CI 0.93-0.99, age ? 60), (c)
      pathogens with general male incidence preponderance (bacterial/parasitic
      infections with campylobacter, Yersinia and Giardia), (d) pathogens with male
      incidence preponderance at juvenile and adult age (sexually transmitted or vector
      borne infections (combined-IRR = 2.53, 95% CI 2.36-2.71, age = 15-59), (e)
      pathogens with male preponderance at older age (tick-borne encephalitis - IRR =
      2.75, 95% CI 1.21-6.24, listeriosis - IRR = 2.06, 95% CI 1.38-3.06, age ? 60).
      Risk factor concepts only partly serve to interpret similarities of grouped
      infections, i.e. transmission-related explanations and sex-specific exposures not
      consistently explain the pattern of food-borne infections (b). Sex-specific
      differences in infectious disease incidence are well acknowledged regarding the
      sexually transmitted diseases. This has led to designing gender-specific
      prevention strategies. Our data suggest that for infections with other
      transmission routes, gender-specific approaches can also be of benefit and
      importance.

PMID- 29357959
TI  - A rare case of a patient with aortic root aneurysm, bicuspid aortic valve, and
      Scimitar syndrome with anomalous venous return to the right superior pulmonary
      vein.
AB  - A rare case of Scimitar Syndrome with an abnormal drainage of the right lower
      pulmonary vein into the right superior pulmonary vein associated with aortic root
      aneurism and bicuspid aortic valve is reported.

PMID- 29357960
TI  - Spiritual care training in healthcare: Does it really have an impact?
AB  - OBJECTIVE: Spiritual care has formed an integral part of palliative care since
      its inception. People with advanced illnesses, however, frequently report that
      their spiritual needs are not attended to by their medical care team. The present
      study examines and describes the impact of a spiritual care training program on
      practice and cultural change in our Canadian hospice. METHOD: A qualitative case
      study approach was adopted to gather feedback from hospice staff and volunteers
      using purposive sampling. In-depth interviews were conducted, transcribed, and
      analyzed using thematic (semantic and latent) analysis. Result Our data suggest
      that the program had a profound personal impact on attendees and contributed to a
      slight shift in practice patterns in our organization. Using a program not
      specifically tailored to our local and organizational cultural contexts resulted
      in some unanticipated challenges such as the range of tensions between personal
      and cultural boundaries. Although some people criticized parts of the program or
      questioned the program's value, a general agreement suggests that the program had
      a positive impact and meaningfully benefited our hospice. "What will happen
      next?" was the question most frequently voiced by interviewees. Significance of
      results Although the program may not have been a perfect fit for our
      organization, its use instigated a process of cultural change that unfolds today.
      The present study suggests that a systematic approach to spiritual care training
      that includes the concepts of workplace spirituality and sensitive practice offer
      useful frameworks for the development and implementation of spiritual care
      training in other institutions.

PMID- 29357961
TI  - Staphylococcus aureus Bloodstream Infection Due to Contaminated Hematopoietic
      Stem-Cell Graft.

PMID- 29357962
TI  - Pyrethroid and carbamate resistance in Australian Helicoverpa armigera
      (Lepidoptera: Noctuidae) from 2008 to 2015: what has changed since the
      introduction of Bt cotton?
AB  - Pyrethroid and carbamate resistance was evaluated in Helicoverpa armigera from
      2008 to 2015. Insects were collected as eggs primarily from cultivated hosts in
      the major cropping areas of New South Wales and Queensland, Australia. Larvae
      reared from eggs were tested for resistance to fenvalerate, bifenthrin or
      methomyl in the F0 generation using a topical application of a discriminating
      dose of insecticide. In 2008-2009, resistance to fenvalerate was 71% and no
      resistance to bifenthrin was recorded. In the following two seasons, resistance
      to pyrethroids was relatively stable with fenvalerate resistance ranging from 63%
      to 67% and bifenthrin resistance ranging from 5.6% and 6.4% in 2009-2010 and 2010
      2011, respectively. However, in 2011-2012, pyrethroid resistance had increased to
      91% and 36% for fenvalerate and bifenthrin, respectively. Resistance remained
      above 90% for fenvalerate and above 35% for bifenthrin in the following three
      seasons from 2012 to 2015. In 2008-2009, methomyl resistance was 33% and declined
      to 22% and 15% in 2009-2010 and 2010-2011, respectively. Methomyl resistance
      remained at moderate levels from 2011-12 to 2014-15, ranging from 21% to 40%.
      Factors that influenced selection pressure of pyrethroid and carbamate
      insecticides and impacted resistance frequency in H. armigera may have been
      associated with changes in the composition of the cropping landscape. The rapid
      expansion of the pulse industry and the commensurate increased use of insecticide
      may have played a role in reselection of high-level pyrethroid resistance, and
      highlights the need for an urgent and strategic response to insecticide
      resistance management in the Australian grains industry.

PMID- 29357965
TI  - Annual Meeting Program.

PMID- 29357963
TI  - Socio-economic status and maternal BMI are associated with duration of breast
      feeding of Norwegian infants.
AB  - OBJECTIVE: To explore whether there is an association between socio-economic
      status and maternal BMI and duration of any breast-feeding/exclusive breast
      feeding among Norwegian infants at 4 and 5 months of age in 2016. DESIGN: Cross
      sectional design. Baseline data from a randomized controlled trial. Data
      concerning breast-feeding were collected by FFQ. SETTING: Recruitment was done at
      child health-care centres and through Facebook in 2016. In total, 960
      infants/parents registered for participating in the study Early Food for Future
      Health. SUBJECTS: A total of 715 infant/mother dyads completed the questionnaire
      when the child was between 5 and 6 months old. RESULTS: At 5 months of age, 81.0
      % of infants were breast-fed and 16.4 % were exclusively breast-fed. Infants of
      highly educated mothers had higher odds of being breast-fed at 5 months compared
      with infants of mothers with less education. Infants of multiparous mothers had
      higher odds of being exclusively breast-fed for the first 5 months compared with
      infants of mothers with one child. Infants of mothers with overweight/obesity had
      reduced odds of both being breast-fed at all and being exclusively breast-fed at
      4 months of age compared with infants of mothers with normal BMI. CONCLUSIONS:
      Our results show that duration of breast-feeding varies with socio-economic
      status and maternal BMI in Norway. Targeting groups with low socio-economic
      status and mothers with overweight or obesity is important, as they are less
      likely to breast-feed according to recommendations.

PMID- 29357966
TI  - [Clinical Study on the Prognosis of Patients with Thymoma with Myasthenia
      Gravis].
AB  - BACKGROUND: Thymoma is frequently associated with myasthenia gravis (MG).
      However, whether MG is a factor for the outcome of patients with thymoma
      following complete thymectomy remains unknown. The aim of this study is to
      investigate the effect of thymoma with MG prognostic factors. METHODS: A
      retrospective analysis of The Chinese Alliance for Research in Thymomas (ChART)
      database within 1992-2012 complete cases 875 cases, 20 years follow-up data
      analysis thymic tumor tissue type credits and MG, Masaoka staging and prognosis,
      postoperative adjuvant therapy and relationship with the prognosis of surgical
      removal of the way. RESULTS: Thymic tumor tissue type credit has correlation with
      MG, difference was statistically significant (chi2=24.908, P<0.001). MG:
      incidence of B2 type (58/178, 32.58%) > B3 type (65/239, 27.20%) > B1 (27/132,
      20.45%) > AB (43/267, 16.10%) > type A, 10.17% (6/59), Masaoka stage has no
      correlation with MG (chi2=0.365, P=1.365). Survival analysis showed that the WHO
      classification, Masaoka stage associated with prognosis (P<0.05), and whether the
      merger MG (chi2=0.113, P=0.736), postoperative adjuvant radiotherapy (chi2=0.380,
      P=0.538) has nothing to do with the prognosis, postoperative adjuvant
      chemotherapy is associated with poor prognosis (chi2=14.417, P<0.001). Whether
      has nothing to do with the prognosis of the thymus resection (chi2=1.548,
      P=1.548), whether the whole correlated with the curative effect of thymus
      excision with MG (chi2=24.695, P<0.001). CONCLUSIONS: Thymoma patients with MG
      and extended thymectomy have no correlation with prognosis. Extended thymectomy
      can improve the effect of MG patients.

PMID- 29357967
TI  - [Prognostic Analysis of Lobectomy versus Sublobar Resection in Patients Aged >=60
      Years with Stage Ia Small Cell Lung Cancer].
AB  - BACKGROUND: Currently, the prognosis of lobectomy and sub-lobectomy for the
      treatment of stage Ia small cell lung cancer (SCLC) is rarely reported. We
      retrospectively studied T1N0M0 (<=3 cm) SCLC patients aged >=60 years, aiming to
      comparatively analyze the prognosis of lobectomy and sub-lobectomy in treating
      patients with Ia SCLC. METHODS: Patients with stage Ia SCLC diagnosed by
      pathologic between 1992 and 2010 were selected from the "Surveillance,
      Epidemiology and End Results database"(SEER). Outcome data were compared using
      Kaplan-Meier (Log-rank test) and Cox model multivariate analysis. RESULTS: We
      identified 515 patients. Median overall survival (OS) of the lobectomy (n=110),
      sublobar resection (n=57) and non-surgical (n=348) cohort were 45, 23 and 16
      months, respectively. The corresponding 5-year OS of the three groups were 44%,
      30%, and 14%, respectively. No significant difference in the prognosis of
      patients with or without lymph node examination/ dissection (P=0.107) and the 5
      year OS of patients underwent lobectomy with chemoradiation was 50%. Cox
      multivariable analysis showed that operation treatment, including lobectomy and
      sublobectomy, was one of the independent factors associated with the prognosis of
      early SCLC patients, and patients undergo lobectomy shows a better OS compared
      with sublobar resection (Lob vs Sub, HR=0.645; 95%CI: 0.433-0.961, P=0.031).
      CONCLUSIONS: For age >=60 years T1N0M0 (<=3 cm) SCLC patients, we recommend
      anatomical lobectomy combined with adjuvant chemoradiation.

PMID- 29357968
TI  - [Analysis of Prognostic Factors and Clinical Characteristics for Patients with
      Limited Stage Small Cell Lung Cancer with Pleural Effusion].
AB  - BACKGROUND: Malignant pleural effusion (PE) was generally defined as pleural
      effusion containing tumors with poor prognosis. Some kinds of undefined pleural
      effusions due to too small amount of effusion had poor prognosis too. This study
      aimed to analyze the clinical characteristics and prognostic factors of patients
      who suffered from limited-stage small cell lung cancer (LS-SCLC) complicated with
      pleural effusion. METHODS: A retrospective analysis included 542 patients who
      were diagnosed with LS-SCLC and had treatment in our hospital from October 2007
      to January 2016. We had observed 109 patients who were diagnosed with pleural
      effusion at their first visit to the doctor. We analyzed the clinical characters,
      survival time and the prognostic factors of the 109 patients. Our main
      observation targets were overall survival (OS) and progression free survival
      (PFS). RESULTS: The median OS and PFS of whole group were 29.4 and 18.2 months.
      Before treatment, survival time of patients with PE were significantly shorter
      than patients without PE (median OS: 21.0 vs 31.7 months; median PFS: 14.1 vs 9.1
      months; Log-rank, P=0.001, P=0.014). Multi-factor analysis of multivariate Cox
      shows PE was the independent prognostic factor of LS-SCLC (P=0.04). Single factor
      analysis showed factors affecting PE patient's survival time included clinical
      stages, lymph node (LN) stages, KPS scores, pulmonary atelectasis and the state
      of pleural after treatment. Cox multi-factor analysis reminded that the state of
      pleural effusion after treatment was the independent prognostic factor of LS-SCLC
      complicated with pleural effusion (P=0.016). There were three groups was
      apportioned patients without pleural effusion before treatment (group 1; n=433),
      patients whose pleural effusion disappeared after treatment (group 2; n=67) and
      patients whose pleural effusion didn't disappear after treatment (group 3;
      n=32).The median OS were 31.7, 23.2, 16.8 months in the group 1, 2, 3 and the
      median PFS were 19.1, 17.9, 11.4 months. Obvious difference was noted by the
      comparison of survival time of these three groups (Log-rank P<0.001, P<0.002).
      The difference between group 2 and group 3 was significant (Log-rank P=0.046,
      P=0.013) while no obvious difference was noted during comparison of group 1 and
      group 2. For patients who have LS-SCLC complicated with PE, there is no
      remarkable difference between chemoradiotherapy and chemotherapy alone.
      CONCLUSIONS: The survival time of patients who suffered from limited-stage small
      cell lung cancer complicated with pleural effusion was obviously shortened. The
      disappearing of pleural effusion after treatment was the independent favorable
      prognostic factor of survival. How to treat needed further investigation.

PMID- 29357969
TI  - [Surgical Procedures and Perioperative Management for Non-small Cell Lung Cancer
      Complicated with Left Atrial Tumor Thrombus].
AB  - BACKGROUND: Non-small cell lung cancer with left atrial tumor thrombus accounts
      for a small proportion of local advanced lung cancer. Whether surgery could bring
      benefits, as well as surgical options are still controversial, and have always
      been hot spots in surgical research. We report a single center experience of
      surgical treatment to non-small cell lung cancer with left atrial tumor thrombus,
      aim to figure out more reasonable treatment strategy. METHODS: From August 2006
      to July 2017, a total of 11 cases of non-small cell lung cancer with left atrial
      tumor thrombus underwent surgery in Thoracic Surgery Department of China-Japan
      Friendship Hospital. Clinical data, treatment options, pathological types and
      prognosis of these patients were collected to perform a retrospective study.
      RESULTS: Of the 11 patients (mean age of 57.9), 7 were men and 4 were women. Six
      of them received neoadjuvant radiotherapy and/or chemotherapy. All patients
      underwent smooth operation, including 3 cases with cardiopulmonary bypass, 1 case
      of posterolateral approach under extracorporeal membrane oxygenation, 6 cases of
      conventional posterolateral approach and 1 case of video-assisted
      minithoracotomy. Nine patients were evaluated as R0 resection while 2 cases were
      evaluated as R1 resection. The Surgeries cost an average of 292 min (210 min-380
      min), with an average of 436 mL (100 mL-1,600 mL) blood loss. One patient (9.1%)
      died within 90 days after surgery, and another 4 cases (36.4%) suffered
      postoperative complications such as arrhythmia, cerebral infarction or hypoxemia.
      Six cases of squamous cell carcinoma, 4 cases of adenocarcinoma and 1 case of
      sarcomatoid carcinoma were identified by pathology. Seven cases were staged as
      pT4N0M0 while 4 cases were staged as pT4N1M0. Nine patients underwent adjuvant
      chemotherapy, and two patients underwent radiotherapy during follow-up. The
      overall follow-up time was 2 to 53 months, the 3-year disease-free survival rate
      was 30.7%, the median disease-free survival time was 31 months, the 3-year
      overall survival rate was 49.1% and the median overall survival time was 33
      months. CONCLUSIONS: For selected patients of non-small cell lung cancer
      complicated with left atrial tumor thrombus, choose a reasonable surgical
      approach to resect both the tumor and the thrombus, strengthen the perioperative
      management and apply neoadjuvant/adjuvant radiotherapy and/or chemotherapy, might
      obtain satisfying prognosis.

PMID- 29357970
TI  - [Epidemiological Evolution of Lung Cancer in the South of Spain from 1990 to
      2010].
AB  - BACKGROUND: Changes in lung cancer has been characterized by the increase of
      cases among women and the increase in adenocarcinomas among other histological
      subtypes. METHODS: Descriptive analysis of cases diagnosed with lung cancer in
      Hospital Virgen de las Nieves (Spain) from 1990 to 2010, based on five variables
      (age, sex, smoking, histology and pathological anatomy). The study establishes
      associations between these variables and compares the results with the
      literature. RESULTS: 2,026 patients were diagnosed with lung cancer in this
      period; 1,838 were males (90.7%) and 188 women (9.3%); 1,892 patients (93.4%)
      were smokers or ex-smokers and 134 (6.6%) had never smoked; the most frequent non
      small cell histology types were squamous cell carcinoma and adenocarcinoma and it
      was the most frequent neoplasia in women and were associated with a lower tobacco
      consumption. CONCLUSIONS: The large majority of lung cancer cases is associated
      with a history of smoking tobacco and there are histopathological differences
      according to gender and cumulative tobacco smoke load.

PMID- 29357971
TI  - [Clinical Observation of Gefitinib with Pericardial Perfusion for ?Advanced Non
      small Cell Lung Cancer].
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) mutation non-small cell lung
      cancer (NSCLC) is an important subtype of lung cancer. The incidence of malignant
      pericardial effusion (MPCE) in EGFR-mutant NSCLC patients is high. However, there
      are few researches on the treatmentof this type of patients. METHODS: We
      collected data on clinical characteristics and treatment of advanced NSCLC
      patients who harboring EGFR mutants and MPCE between January 2010 and December
      2016. The treatments were divided into three groups: oral gefitinib combined with
      pericardial perfusion of hydroxycamptotheci (HCPT) group (gefitinib/HCPT);
      intravenous chemotherapy combined with pericardial perfusion of HCPT group
      (chemotherapy/HCPT) and gefitinib monotherapy group. And we retrospectively
      analyzed patients' outcomes in three groups. RESULTS: In 273 advanced NSCLC
      patients with EGFR mutations, 29 cases had pericardial effusion, among which 6
      patients with small amount of pericardial effusion were excluded, and 23 patients
      were analyzed. Median pericardium progression free survival (PFS) was 247 days.
      PFS for gefitinib/HCPT group (460 days) was superior to PFS for chemotherapy/HCPT
      group (94 days, P=0.008) and gefitinib monotherapy group (131 days, P=0.032). As
      for the efficacy of primary pulmonary lesions, the efficacy in gefitinib/ HCPT
      group was superior to chemotherapy/HCPT group [objective response rate (ORR):
      33.3% vs 12.5%; disease control rate (DCR): 86.7% vs 62.5%]. There is no
      difference of ORR and DCR between gefitinib/HCPT group and gefitinib monotherapy
      group. No obvious adverse reaction was observed in all three groups. CONCLUSIONS:
      First-line gefitinib therapy combined with pericardial perfusion of HCPT can
      improve pericardium PFS for advanced NSCLC patients who harboring EGFR mutants
      andmalignantpericardial effusion. This finding should be confirmed further
      through multicenter, prospective clinical trials with large sample size.

PMID- 29357972
TI  - [Progress of Long Non-coding RNA in Non-small Cell Lung Cancer].
AB  - Lung cancer is one of the most important malignant tumors in the world. The
      morbidity and mortality rank the first in all kinds of cancer. Long non-coding
      RNA (lncRNA) is at least 200 nt long and has no protein coding capacity. It plays
      an important role in the epigenetic regulation, cell cycle regulation, the
      regulation of cell differentiation, and many other life activities. The studies
      indicate that dysregulation of lncRNAs in non-small cell lung cancer (NSCLC)
      tissue and blood circulation is associated with the occurrence and development of
      cancer. The lncRNAs play an significant role in proliferation, differentiation,
      migration and apoptosis of the tumor cells. Explore the potential mechanism
      between lncRNAs and NSCLC is beneficial for the early diagnosis, target therpy
      and improve prognosis. Therefore, the study aims to demonstrate the latest
      studies on the lncRNAs related to occurence, diagnosis, therpy and prognosis of
      NSCLC. It can help to deeply understanding of lncRNA, and provide new ideas for
      the prevention of NSCLC.

PMID- 29357973
TI  - [Circular RNA in Lung Cancer Research: Biogenesis, Functions and Roles].
AB  - Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer
      death in China. In recent years, therapies for oncogenedrivers and immune
      checkpoints have proved inspiring. Circular RNA (circRNA), which is a kind of RNA
      with covalent ring structure relating to stages and metastasis of cancer, has
      many special biological functions in physiological processes, diseases and so on.
      Thus, circRNA is expected to be a potential biomarker for cancer prediction and
      treatment in view of its high conservation and tissue-specific. However, function
      analysis and regulatory mechanism of circRNA in lung cancer come so far remains
      unclear and limited literatures are available. In this review, we highlight the
      research history, formation mechanism, biological function of circRNA and
      research progress in cancer, especially in lung cancer. We mean to provide
      theoretical evidences and new ideas for researches on circRNAs in lung cancer.

PMID- 29357974
TI  - [Research Progress in the Therapeutic Strategy Based on Targeting at ?Lung Cancer
      Stem Cell].
AB  - With high morbidity and mortality, lung cancer is a major threat to human health
      and one of the focuses of tumor researches. Lung cancer stem cells (LCSCs) are
      regarded as a subpopulation of cells within lung cancer tissues with the capacity
      of self-renewal and differentiation, and might be related to tumorigenesis and
      heterogeneity of lung cancer. Tumor recurrence, metastasis and drug resistance of
      lung cancers could be clarified by LCSC hypothesis. Thus it's therapeutically
      prospective to target at these cells. This review summarizes the biomarkers of
      LCSCs and their aberrant signal pathways, as well as the therapeutic strategies
      targeting at LCSCs.

PMID- 29357975
TI  - [Targeting of the AKT/m-TOR Pathway: Biomarkers of Resistance to Cancer Therapy-
      ?AKT/m-TOR Pathway and Resistance to Cancer Therapy].
AB  - Resistance to cancer therapy continues to be a major limitation for the
      successful treatment of cancer. There are many published studies on therapy
      resistance in breast and prostate cancers; however, there are currently no data
      on molecular markers associated with resistance. The conflicting data were
      reported regarding the AKT/m-TOR signaling pathway components as markers
      predicting resistance. The AKT/m-TOR signaling pathway is involved in the
      development of many human cancers; its activation is related to cell
      proliferation, angiogenesis, apoptosis, as well as to therapy resistance.
      Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to
      identify universal markers associated with the development of resistance to
      cancer therapy.

PMID- 29357977
TI  - Evolutionary Rewiring of Human Regulatory Networks by Waves of Genome Expansion.
AB  - Genome expansion is believed to be an important driver of the evolution of gene
      regulation. To investigate the role of a newly arising sequence in rewiring
      regulatory networks, we estimated the age of each region of the human genome by
      applying maximum parsimony to genome-wide alignments with 100 vertebrates. We
      then studied the age distribution of several types of functional regions, with a
      focus on regulatory elements. The age distribution of regulatory elements reveals
      the extensive use of newly formed genomic sequence in the evolution of regulatory
      interactions. Many transcription factors have expanded their repertoire of
      targets through waves of genomic expansions that can be traced to specific
      evolutionary times. Repeated elements contributed a major part of such expansion:
      many classes of such elements are enriched in binding sites of one or a few
      specific transcription factors, whose binding sites are localized in specific
      portions of the element and characterized by distinctive motif words. These
      features suggest that the binding sites were available as soon as the new
      sequence entered the genome, rather than being created later by accumulation of
      point mutations. By comparing the age of regulatory regions to the evolutionary
      shift in expression of nearby genes, we show that rewiring through genome
      expansion played an important role in shaping human regulatory networks.

PMID- 29357976
TI  - Variation in natural exposure to anopheles mosquitoes and its effects on malaria
      transmission.
AB  - Variation in biting frequency by Anopheles mosquitoes can explain some of the
      heterogeneity in malaria transmission in endemic areas. In this study in Burkina
      Faso, we assessed natural exposure to mosquitoes by matching the genotype of
      blood meals from 1066 mosquitoes with blood from residents of local households.
      We observed that the distribution of mosquito bites exceeded the Pareto rule
      (20/80) in two of the three surveys performed (20/85, 76, and 96) and, at its
      most pronounced, is estimated to have profound epidemiological consequences,
      inflating the basic reproduction number of malaria by 8-fold. The distribution of
      bites from sporozoite-positive mosquitoes followed a similar pattern, with a
      small number of individuals within households receiving multiple potentially
      infectious bites over the period of a few days. Together, our findings indicate
      that heterogeneity in mosquito exposure contributes considerably to heterogeneity
      in infection risk and suggest significant variation in malaria transmission
      potential.

PMID- 29357979
TI  - Discussion of "Patient navigation reduces time to care for patients with breast
      symptoms and abnormal screening mammograms".

PMID- 29357978
TI  - Reccurrent F8 Intronic Deletion Found in Mild Hemophilia A Causes Alu
      Exonization.
AB  - Incorporation of distant intronic sequences in mature mRNA is an underappreciated
      cause of genetic disease. Several disease-causing pseudoexons have been found to
      contain repetitive elements such as Alu elements. This study describes an
      original pathological mechanism by which a small intronic deletion leads to Alu
      exonization. We identified an intronic deletion, c.2113+461_2113+473del, in the
      F8 intron 13, in two individuals with mild hemophilia A. In vivo and in vitro
      transcript analysis found an aberrant transcript, with an insertion of a 122-bp
      intronic fragment (c.2113_2114ins2113+477_2113+598) at the exon 13-14 junction.
      This out-of-frame insertion is predicted to lead to truncated protein
      (p.Gly705Aspfs*37). DNA sequencing analysis found that the pseudoexon corresponds
      to antisense AluY element and the deletion removed a part of the poly(T)-tail
      from the right arm of these AluY. The heterogenous nuclear riboprotein C1/C2
      (hnRNP C) is an important antisense Alu-derived cryptic exon silencer and binds
      to poly(T)-tracts. Disruption of the hnRNP C binding site in AluY T-tract by
      mutagenesis or hnRNP C knockdown using siRNA in HeLa cells reproduced the effect
      of c.2113+461_2113+473del. The screening of 114 unrelated families with mild
      hemophilia A in whom no genetic event was previously identified found a deletion
      in the poly(T)-tail of AluY in intron 13 in 54% of case subjects (n = 61/114). In
      conclusion, this study describes a deletion leading to Alu exonization found in
      6.1% of families with mild hemophila A in France.

PMID- 29357980
TI  - On the low dimensionality of behavioral deficits and alterations of brain network
      connectivity after focal injury.
AB  - Traditional neuropsychological approaches emphasize the specificity of behavioral
      deficits and the modular organization of the brain. At the population level,
      however, there is emerging evidence that deficits are correlated resulting in a
      low dimensional structure of post-stroke neurological impairments. Here we
      consider the implications of low dimensionality for the three-way mapping between
      structural damage, altered physiology, and behavioral deficits. Understanding
      this mapping will be aided by large-sample studies that apply multivariate models
      and focus on explained percentage of variance, as opposed to univariate lesion
      symptom techniques that report statistical significance. The low dimensionality
      of behavioral deficits following stroke is paralleled by widespread, yet
      relatively consistent, changes in functional connectivity (FC), including a
      reduction in modularity. Both are related to the structural damage to white
      matter and subcortical grey commonly produced by stroke. We suggest that large
      scale physiological abnormalities following a stroke reduce the variety of neural
      states visited during task processing and at rest, resulting in a limited
      repertoire of behavioral states.

PMID- 29357981
TI  - Median and Dorsal Raphe Serotonergic Neurons Control Moderate Versus Compulsive
      Cocaine Intake.
AB  - BACKGROUND: Reduced expression of the serotonin transporter (SERT) promotes
      anxiety and cocaine intake in both humans and rats. We tested the hypothesis that
      median raphe nucleus (MRN) and dorsal raphe nucleus (DRN) serotonergic
      projections differentially mediate these phenotypes. METHODS: We used virally
      mediated RNA interference to locally downregulate SERT expression and compared
      the results with those of constitutive SERT knockout. Rats were allowed either
      short access (ShA) (1 hour) or long access (LgA) (6 hours) to cocaine self
      administration to model moderate versus compulsive-like cocaine taking. RESULTS:
      SERT knockdown in the MRN increased cocaine intake selectively under ShA
      conditions and, like ShA cocaine self-administration, reduced corticotropin
      releasing factor (CRF) immunodensity in the paraventricular nucleus of the
      hypothalamus. In contrast, SERT knockdown in the DRN increased cocaine intake
      selectively under LgA conditions and, like LgA cocaine self-administration,
      reduced CRF immunodensity in the central nucleus of the amygdala. SERT knockdown
      in the MRN or DRN produced anxiety-like behavior, as did withdrawal from ShA or
      LgA cocaine self-administration. The phenotype of SERT knockout rats was a
      summation of the phenotypes generated by MRN- and DRN-specific SERT knockdown.
      CONCLUSIONS: Our results highlight a differential role of serotonergic
      projections arising from the MRN and DRN in the regulation of cocaine intake. We
      propose that a cocaine-induced shift from MRN-driven serotonergic control of CRF
      levels in the hypothalamus to DRN-driven serotonergic control of CRF levels in
      the amygdala may contribute to the transition from moderate to compulsive intake
      of cocaine.

PMID- 29357982
TI  - Altered Gradients of Glutamate and Gamma-Aminobutyric Acid Transcripts in the
      Cortical Visuospatial Working Memory Network in Schizophrenia.
AB  - BACKGROUND: Visuospatial working memory (vsWM), which is impaired in
      schizophrenia, requires information transfer across multiple nodes in the
      cerebral cortex, including visual, posterior parietal, and dorsolateral
      prefrontal regions. Information is conveyed across these regions via the
      excitatory projections of glutamatergic pyramidal neurons located in layer 3,
      whose activity is modulated by local inhibitory gamma-aminobutyric acidergic
      (GABAergic) neurons. Key properties of these neurons differ across these cortical
      regions. Consequently, in schizophrenia, alterations in the expression of gene
      products regulating these properties could disrupt vsWM function in different
      ways, depending on the region(s) affected. METHODS: Here, we quantified the
      expression of markers of glutamate and GABA neurotransmission selectively in
      layer 3 of four cortical regions in the vsWM network from 20 matched pairs of
      schizophrenia and unaffected comparison subjects. RESULTS: In comparison
      subjects, levels of glutamate transcripts tended to increase, whereas GABA
      transcript levels tended to decrease, from caudal to rostral, across cortical
      regions of the vsWM network. Composite measures across all transcripts revealed a
      significant effect of region, with the glutamate measure lowest in the primary
      visual cortex and highest in the dorsolateral prefrontal cortex, whereas the GABA
      measure showed the opposite pattern. In schizophrenia subjects, the expression
      levels of many of these transcripts were altered. However, this disease effect
      differed across regions, such that the caudal-to-rostral increase in the
      glutamate measure was blunted and the caudal-to-rostral decline in the GABA
      measure was enhanced in the illness. CONCLUSIONS: Differential alterations in
      layer 3 glutamate and GABA neurotransmission across cortical regions may
      contribute to vsWM deficits in schizophrenia.

PMID- 29357983
TI  - Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF)
      on activation and functional properties of human T cell subpopulations in vitro.
AB  - We investigated the direct effects of human granulocyte colony-stimulating factor
      (G-CSF) on functionality of human T-cell subsets. CD3+ T-lymphocytes were
      isolated from blood of healthy donors by positive magnetic separation. T cell
      activation with particles conjugated with antibodies (Abs) to human CD3, CD28 and
      CD2 molecules increased the proportion of cells expressing G-CSF receptor (G
      CSFR, CD114) in all T cell subpopulations studied (CD45RA+/CD197+ naive T cells,
      CD45RA-/CD197+ central memory T cells, CD45RA-/CD197- effector memory T cells and
      CD45RA+/CD197- terminally differentiated effector T cells). Upon T-cell
      activation in vitro, G-CSF (10.0 ng/ml) significantly and specifically enhanced
      the proportion of CD114+ T cells in central memory CD4+ T cell compartment. A
      dilution series of G-CSF (range, 0.1-10.0 ng/ml) was tested, with no effect on
      the expression of CD25 (interleukin-2 receptor alpha-chain) on activated T cells.
      Meanwhile, G-CSF treatment enhanced the proportion of CD38+ T cells in CD4+ naive
      T cell, effector memory T cell and terminally differentiated effector T cell
      subsets, as well as in CD4- central memory T cells and terminally differentiated
      effector T cells. G-CSF did not affect IL-2 production by T cells; relatively low
      concentrations of G-CSF down-regulated INF-gamma production, while high
      concentrations of this cytokine up-regulated IL-4 production in activated T
      cells. The data obtained suggests that G-CSF could play a significant role both
      in preventing the development of excessive and potentially damaging inflammatory
      reactivity, and in constraining the expansion of potentially cytodestructive T
      cells.

PMID- 29357984
TI  - Do Children With Type 2 Diabetes in Canada Have Access to Safe and Effective
      Treatment Options?

PMID- 29357986
TI  - A Metasynthesis: Uncovering What Is Known About the Experiences of Families With
      Children Who Have Life-limiting and Life-threatening Illnesses.
AB  - PURPOSE: To conduct a metasynthesis of qualitative research exploring parents'
      psychosocial experiences during complex and traumatic life transitions related to
      caring for a child with a life-limiting (LLI) or life-threatening illness (LTI).
      BACKGROUND: Parents' experiences of caring for a child impacted by an LLI or LTI
      are not clearly understood, and holistic, comprehensive pediatric nursing care
      for parents who have children with LLI and LTIs continues to be developed as
      treatment improves and survival is extended. REVIEW METHODS: Predetermined
      inclusion and exclusion criteria were used to review qualitative studies. Those
      included were appraised, classified, and synthesized using systematic procedures
      guided by Sandelowski and Barroso (2006). DATA SOURCES: A systematic search of
      qualitative research was conducted by an experienced librarian to identify and
      retrieve studies from 10 databases. RESULTS: Of the 3515 studies screened, 23
      were included. A synthesis of the findings demonstrated that parents experience
      profound and pervasive uncertainty, leading to their own illness experience being
      described as a dual reality in which fighting for survival and recognizing the
      threat of their child's death were daily challenges. Three key processes emerged:
      the devastation of living with uncertainty, the emergence of hope, and moving
      forward. CONCLUSION: The integration of findings adds to the current body of
      knowledge by highlighting the very complex experiences that parents undergo.
      These findings can support a more comprehensive pediatric nursing plan of care
      that accounts for the intricacies of the parental experience and the importance
      of hope.

PMID- 29357985
TI  - Qualitative Analysis of Pediatric Patient and Caregiver Perspectives After Recent
      Diagnosis With Inflammatory Bowel Disease.
AB  - PURPOSE: A diagnosis of a chronic illness is a life-altering experience for a
      child and his or her family. The purpose of this study was to elicit children and
      parent perspectives following a diagnosis of Inflammatory Bowel Disease (IBD).
      DESIGN & METHODS: A qualitative description design was employed. Eighteen
      patients were recruited from a Pediatric IBD Clinic in Western Canada. Interviews
      were used to gather perceptions, opinions, and attitudes from children and their
      parents. Transcriptions of the interviews were analyzed using a qualitative
      content analysis. RESULTS: Four themes were identified: perspective of diagnosis,
      roles in care and decision-making, sharing the diagnosis, and treating the
      disease. Children and parents expressed varied emotions in response to diagnosis.
      Families articulated the desire to become more active members in the decision
      making process on treatment choices. While using conventional medical therapy was
      seen as an appropriate choice for short-term therapy, many parents hoped that
      more non-conventional and alternative therapies could be used in the future.
      CONCLUSION: Healthcare providers need to provide excellent education on the
      disease process, treatment options, and the use of CAM therapy in IBD, while at
      the same time supporting children and parent's voices in treatment decisions.
      PRACTICE IMPLICATIONS: Improvement strategies need to be implemented to allow
      families to feel that they have a voice when making decisions regarding treatment
      options. Families need to be educated and supported on the use of CAM therapies
      in IBD.

PMID- 29357988
TI  - GESIDA/PETHEMA recommendations on the diagnosis and treatment of lymphomas in
      patients infected by the human immunodeficiency virus.
AB  - The incidence of non-Hodgkin's lymphoma and Hodgkin's lymphoma is higher in
      patients with HIV infection than in the general population. Following the
      introduction of combination antiretroviral therapy (cART), the prognostic
      significance of HIV-related variables has decreased, and lymphoma-related factors
      have become more pronounced. Currently, treatments for lymphomas in HIV-infected
      patients do not differ from those used in the general population. However,
      differentiating characteristics of seropositive patients, such as the need for
      cART and specific prophylaxis and treatment of certain opportunistic infections,
      should be considered. This document updates recommendations on the diagnosis and
      treatment of lymphomas in HIV infected patients published by GESIDA/PETHEMA in
      2008.

PMID- 29357987
TI  - Patient Perspectives on Nurse-led Consultations Within a Pilot Structured
      Transition Program for Young Adults Moving From an Academic Tertiary Setting to
      Community-based Type 1 Diabetes Care.
AB  - PURPOSE: We aimed to evaluate patient self-management activities, patient
      perceptions of the therapeutic relationship and satisfaction with nurse-led
      consultations as part of a structured, pilot program transitioning young adults
      with type 1 diabetes (T1DM) to adult-oriented community-based practices. DESIGN
      AND METHODS: A descriptive, cross-sectional study of patients receiving nurse-led
      consultations. Patients provided sociodemographic/health information, glycated
      hemoglobin (HbA1c) measures and completed questionnaires assessing self
      management (Revised Self-Care Inventory) and the therapeutic relationship (Caring
      Nurse-Patient Interaction - short scale). HbA1c values were compared to guideline
      recommendations. RESULTS: Twenty patients participated. HbA1c was <=7.5% in 3/14
      (21%) and 5/14 (36%) exhibited poor glycemic control (>=9.5%). The greatest
      concordance for self-care was in relation to insulin therapy (4.5+/-0.5) while
      patients reported the lowest adherence to diet recommendations (2.9+/-0.8).
      Overall satisfaction with nurse-led consultations was high (4+/-0.5 out of 5).
      Patients considered diabetes knowledge and technical competence as very important
      and were most pleased with the humanistic aspects of nursing care. Respect for
      privacy was deemed the most important (and most frequently observed) nursing
      attitude/behavior during consultations. CONCLUSIONS: Young adults found the nurse
      led consultations with therapeutic education to develop T1DM self-care skills are
      an important complement to medical management during transition. PRACTICE
      IMPLICATIONS: Patient autonomy and privacy should be respected during this
      developmental period. Nurses taking a humanistic approach towards accompanying
      and supporting the patient can enhance the therapeutic relationship during
      transition and promote continuity of care. Transition nurses can use technical
      competence and therapeutic education to empower patients for self-management.

PMID- 29357989
TI  - Does visual letter similarity modulate masked form priming in young readers of
      Arabic?
AB  - We carried out a masked priming lexical decision experiment to study whether
      visual letter similarity plays a role during the initial phases of word
      processing in young readers of Arabic (fifth graders). Arabic is ideally suited
      to test these effects because most Arabic letters share their basic shape with at
      least one other letter and differ only in the number/position of diacritical
      points (e.g., ? - ? ;? - ? ;? - ? ;? - ? - ? ? ;? - ? ;? - ? - ? ;? - ? ;? - ? ;?
      - ?). We created two one-letter-different priming conditions for each target
      word, in which a letter from the consonantal root was substituted by another
      letter that did or did not keep the same shape (e.g., ???? - ???? vs. ???? -
      ????). Another goal of the current experiment was to test the presence of masked
      orthographic priming effects, which are thought to be unreliable in Semitic
      languages. To that end, we included an unrelated priming condition. We found a
      sizable masked orthographic priming effect relative to the unrelated condition
      regardless of visual letter similarity, thereby revealing that young readers are
      able to quickly process the diacritical points of Arabic letters. Furthermore,
      the presence of masked orthographic priming effects in Arabic suggests that the
      word identification stream in Indo-European and Semitic languages is more similar
      than previously thought.

PMID- 29357990
TI  - Generalized trust predicts young children's willingness to delay gratification.
AB  - Young children's willingness to delay gratification by forgoing an immediate
      reward to obtain a more desirable one in the future predicts a wide range of
      positive social, cognitive, and health outcomes. Standard accounts of this
      phenomenon have focused on individual differences in cognitive control skills
      that allow children to engage in goal-oriented behavior, but recent findings
      suggest that person-specific trust is also important, with children showing a
      stronger tendency to delay gratification if they have reason to trust the
      individual who is promising the future reward. The current research builds on
      those findings by examining generalized trust, which refers to the extent to
      which others are generally viewed as trustworthy. A total of 150 3- to 5-year
      olds in China were tested. Participants were given the opportunity to obtain one
      sticker immediately, or wait for 15 min for two stickers. Results showed that
      participants with high levels of generalized trust waited longer even after
      controlling for age and level of executive function. These results suggest that
      trust plays a role in delaying gratification even when children have no
      information about the individual who is promising the future reward. More
      broadly, the findings build on recent evidence that there is more to delay of
      gratification than cognitive capacity, and they suggest that there are individual
      differences in whether children consider sacrificing for a future outcome to be
      worth the risk.

PMID- 29357991
TI  - Feasibility of medical stone amendment for sewage sludge co-composting and
      production of nutrient-rich compost.
AB  - The feasibility of medical stone (MS) amendment as an innovative additive for
      dewatered fresh sewage sludge (DFSS) co-composting was assessed using a 130-L
      vessel-scale composter. To verify successful composting, five treatments were
      designed with four different dosages (2, 4, 6, and 10) % of MS with a 1:1 mixture
      (dry weight) of DFSS + wheat straw (WS). The WS was used as a bulking agent. A
      control without any amendment treatment was carried out for the purpose of
      comparison. For DFSS co-composting, the amendment with MS improved the
      mineralization efficiency and compost quality in terms of CO2 emissions,
      dehydrogenase enzyme (DE), electrical conductivity (EC), water-solubility, and
      total nutrients transformation. The DTPA-extractable Cu and Zn were also
      estimated to confirm the immobilization ability of the applied MS. Seed
      germination and plant growth tests were conducted to ensure the compost stability
      and phytotoxicity for Chinese cabbage (Brassica rapa chinensis L.) growth and
      biomass, as well as chlorophyll content. The results showed that during the bio
      oxidative phase, DOC, DON, AP, NH4+-N, and NO3--N increased drastically in all
      the MS-blended treatments, except the application of 2% MS and the control
      treatment; significantly lower water-soluble nutrients were observed in the 2% MS
      and control treatments. A novel additive with 6-10% MS dosages considerably
      enhanced the organic matter conversion in the stable end-product (compost) and
      reduced the maturity period by two weeks compared to the 2% MS and control
      treatments. Consequently, the maturity parameters (e.g., EC, SGI, NH4+-N, DOC,
      and DON) confirmed that compost with 6-10% MS became more stable and mature
      within four weeks of DFSS co-composting. At the end of composting, significantly
      higher DTPA-extractable Cu and Zn contents were observed in the control
      treatment, and subsequently, in the very low application (10%) of MS. Higher MS
      dosage lowered the pH and EC to within the permissible limit compared to the
      control, while increased concentrations of water-soluble nutrients diminished the
      DTPA-extractable Cu and Zn contents. In addition, plant growth experiments
      demonstrated that the addition of compost with 150 kg ha-1 TKN improved the
      Chinese cabbage biomass and chlorophyll level. The highest dry weight biomass
      (2.78 +/- 0.02 g/pot) was obtained with 6% MS-blended compost while the maximum
      chlorophyll content was found with application of 4% MS compost (41.84 SPAD-unit)
      for Chinese cabbage. Therefore, 6-10% MS can be recommended to improve DFSS
      composting and to reduce the period to maturity by two weeks when considering its
      composting effect on Chinese cabbage growth, biomass yield, and chlorophyll
      level. However, amendment with 6% MS is a more economically feasible approach for
      DFSS co-composting.

PMID- 29357992
TI  - Force required for correcting the deformity of pectus carinatum and related
      multivariate analysis.
AB  - OBJECTIVE: To measure the force required for correcting pectus carinatum to the
      desired position and investigate the correlations of the required force with
      patients' gender, age, deformity type, severity and body mass index (BMI).
      METHODS: A total of 125 patients with pectus carinatum were enrolled in the study
      from August 2013 to August 2016. Their gender, age, deformity type, severity and
      BMI were recorded. A chest wall compressor was used to measure the force required
      for correcting the chest wall deformity. Multivariate linear regression was used
      for data analysis. RESULTS: Among the 125 patients, 112 were males and 13 were
      females. Their mean age was 13.7+/-1.5 years old, mean Haller index was 2.1+/
      0.2, and mean BMI was 17.4+/-1.8 kg/m2. Multivariate linear regression analysis
      showed that the desirable force for correcting chest wall deformity was not
      correlated with gender and deformity type, but positively correlated with age and
      BMI and negatively correlated with Haller index. CONCLUSIONS: The desirable force
      measured for correcting chest wall deformities of patients with pectus carinatum
      positively correlates with age and BMI and negatively correlates with Haller
      index. The study provides valuable information for future improvement of
      implanted bar, bar fixation technique, and personalized surgery. TYPE OF STUDY:
      Retrospective study. LEVEL OF EVIDENCE: Level 3-4.

PMID- 29357993
TI  - Long-term exposure to fine particulate matter air pollution and type 2 diabetes
      mellitus in elderly: A cohort study in Hong Kong.
AB  - BACKGROUND: Evidence for the link between long-term air pollution exposure and
      occurrence of diabetes is limited and the results are mixed. OBJECTIVES: We aimed
      to assess the association of long-term residential exposure to fine particulate
      matter (PM2.5) with the prevalence and incidence of type 2 diabetes mellitus
      (DM). METHODS: This is a prospective cohort study. We studied 61,447 participants
      of the Chinese Elderly Health Services cohort in Hong Kong enrolled 1998-2001 and
      followed participants without DM at baseline to 31 December 2010 to ascertain the
      first hospital admissions for type 2 DM. Yearly mean residential PM2.5 exposure
      was predicted based on satellite data. Logistic regression and time-varying Cox
      regression model were used to evaluate the prevalence and incidence risk of DM
      associated with PM2.5 while adjusting for potential individual and neighborhood
      confounders. RESULTS: There were 61,447 participants included in the study of
      prevalent DM, and in 53,905 participants without DM at baseline we studied
      incident type 2 DM. Over a mean follow-up of 9.8 years, we ascertained 806
      incident cases of type 2 DM. After adjusting for potential confounders, the odds
      ratio (OR) for every interquartile range (3.2 MUg/m3) increase of PM2.5
      concentration was 1.06 (95% confidence interval (CI): 1.01-1.11) for prevalent
      DM, while the corresponding hazard ratio (HR) was 1.15 (95% CI: 1.05-1.25) for
      incident type 2 DM. CONCLUSIONS: Long-term exposure to high levels of PM2.5 may
      increase the risk of both prevalence and incidence of type 2 diabetes mellitus in
      Hong Kong elderly population.

PMID- 29357994
TI  - Severe pulmonary emphysema in a young patient with vasculitis associated with
      proteinase-3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA).

PMID- 29357995
TI  - Neutrophilic Asthma.

PMID- 29357996
TI  - Peroneus brevis tendon in proximal 5th metatarsal fractures: Anatomical
      considerations for safe hook plate placement.
AB  - INTRODUCTION: The peroneus brevis tendon (PBT) inserts into the proximal aspect
      of the 5th metatarsal. Metatarsal bone fractures are encountered to be the most
      common fractures in the foot with predominantly fractures at the base of the
      fifth metatarsal bone. Mechanism of injury and treatment of the proximal 5th
      metatarsal fractures vary due to the complex anatomy and diverse biomechanical
      properties. The purpose of this study was to analyze the footprint of the PBT
      with regards to the proximal 5th metatarsal fractures and to define a "safe zone"
      for hook plate placement. MATERIALS AND METHODS: Forty-one (41) fixed human lower
      leg specimens were dissected to expose the PBT insertion. The following footprint
      characteristics were evaluated: area of insertion (AOI) (mm2), length (mm), width
      (mm), shape and insertional variations. The position of the main PBT footprint
      was localized according to the Lawrence and Botte classification for the proximal
      5th metatarsal fractures (Zone I-III). A "safe zone" was defined for the fracture
      specific hook plate placement. RESULTS: In 25 (61%) feet the PBT footprint was
      situated in Zone I and in 16 feet (39%) in Zone I&II. The mean AOI, length and
      width measured 54.5 mm2 (SD 16.5), 16.0 mm (SD 5.1) and 4.7 mm (SD 1.4),
      respectively. Analysis of the footprint shapes revealed four different shape
      types: kidney (29.3%), diamond (22.0%), crescent (31.7%) and oval (17.0%). A
      "safe zone" for hook plate placement without or minimal interference of the PBT
      at its insertion could be defined at the lateral aspect of the 5th metatarsal.
      CONCLUSION: The majority of the PBT footprints were found in Zone I. Hook plate
      placement demonstrated to be safe when placed strictly laterally at the proximal
      aspect of the 5th metatarsal. Precise knowledge of the peroneus brevis anatomy
      may help to better understand the biomechanical aspects of the proximal 5th
      metatarsal fractures.

PMID- 29357997
TI  - Year-round presence of neonicotinoid insecticides in tributaries to the Great
      Lakes, USA.
AB  - To better characterize the transport of neonicotinoid insecticides to the world's
      largest freshwater ecosystem, monthly samples (October 2015-September 2016) were
      collected from 10 major tributaries to the Great Lakes, USA. For the monthly
      tributary samples, neonicotinoids were detected in every month sampled and five
      of the six target neonicotinoids were detected. At least one neonicotinoid was
      detected in 74% of the monthly samples with up to three neonicotinoids detected
      in an individual sample (10% of all samples). The most frequently detected
      neonicotinoid was imidacloprid (53%), followed by clothianidin (44%),
      thiamethoxam (22%), acetamiprid (2%), and dinotefuran (1%). Thiacloprid was not
      detected in any samples. The maximum concentration for an individual
      neonicotinoid was 230 ng L-1 and the maximum total neonicotinoids in an
      individual sample was 400 ng L-1. The median detected individual neonicotinoid
      concentrations ranged from non-detect to 10 ng L-1. The detections of
      clothianidin and thiamethoxam significantly increased as the percent of
      cultivated crops in the basins increased (rho = 0.73, P = .01; rho = 0.66, P =
      .04, respectively). In contrast, imidacloprid detections significantly increased
      as the percent of the urbanization in the basins increased (rho = 0.66, P = .03).
      Neonicotinoid concentrations generally increased in spring through summer
      coinciding with the planting of neonicotinoid-treated seeds and broadcast
      applications of neonicotinoids. More spatially intensive samples were collected
      in an agriculturally dominated basin (8 sites along the Maumee River, Ohio) twice
      during the spring, 2016 planting season to provide further information on
      neonicotinoid inputs to the Great Lakes. Three neonicotinoids were ubiquitously
      detected (clothianidin, imidacloprid, thiamethoxam) in all water samples
      collected within this basin. Maximum individual neonicotinoid concentrations was
      330 ng L-1 and maximum total neonicotinoid concentration was 670 ng L-1; median
      detected individual neonicotinoid concentrations were 7.0 to 39 ng L-1.

PMID- 29357998
TI  - [WebSurvCa: web-based estimation of death and survival probabilities in a
      cohort].
AB  - Relative survival has been used as a measure of the temporal evolution of the
      excess risk of death of a cohort of patients diagnosed with cancer, taking into
      account the mortality of a reference population. Once the excess risk of death
      has been estimated, three probabilities can be computed at time T: 1) the crude
      probability of death associated with the cause of initial diagnosis (disease
      under study), 2) the crude probability of death associated with other causes, and
      3) the probability of absolute survival in the cohort at time T. This paper
      presents the WebSurvCa application (https://shiny.snpstats.net/WebSurvCa/),
      whereby hospital-based and population-based cancer registries and registries of
      other diseases can estimate such probabilities in their cohorts by selecting the
      mortality of the relevant region (reference population).

PMID- 29357999
TI  - Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative
      Colitis (GETECCU) on the use of thiopurines in inflammatory bowel disease.
AB  - Thiopurines (azathioprine and mercaptopurine) are widely used in patients with
      inflammatory bowel disease. In this paper, we review the main indications for
      their use, as well as practical aspects on efficacy, safety and method of
      administration. They are mainly used to maintain remission in steroid-dependent
      disease or with ciclosporin to control a severe ulcerative colitis flare-up, as
      well as to prevent postoperative Crohn's disease recurrence, and also in
      combination therapy with biologics. About 30-40% of patients will not respond to
      treatment and 10-20% will not tolerate it due to adverse effects. Before they are
      prescribed, immunisation status against certain infections should be checked.
      Determination of thiopurine methyltransferase activity (TPMT) is not mandatory
      but it increases initial safety. The appropriate dose is 2.5mg/kg/day for
      azathioprine and 1.5mg/kg/day for mercaptopurine. Some adverse effects are
      idiosyncratic (digestive intolerance, pancreatitis, fever, arthromyalgia, rash
      and some forms of hepatotoxicity). Others are dose-dependent (myelotoxicity and
      other types of hepatotoxicity), and their surveillance should never be
      interrupted during treatment. If therapy fails or adverse effects develop,
      management can include switching from one thiopurine to the other, reducing the
      dose, combining low doses of azathioprine with allopurinol and assessing
      metabolites, before their use is ruled out. Non-melanoma skin cancer, lymphomas
      and urinary tract tumours have been linked to thiopurine therapy. Thiopurine use
      is safe during conception, pregnancy and breastfeeding.

PMID- 29358000
TI  - Detection and management of cardiomyopathy in female dystrophinopathy carriers.
AB  - Regular health checkups for mothers of patients with Duchenne muscular dystrophy
      have been performed at National Hospital Organization Tokushima Hospital since
      1994. Among 43 mothers participated in this study, 28 dystrophinopathy carriers
      were identified. Skeletal and cardiac muscle functions of these subjects were
      examined. High serum creatine kinase was found in 23 subjects (82.1%). Obvious
      muscle weakness was present in 5 (17.8%) and had progressed from 1994 to 2015.
      Cardiomyopathy was observed in 15 subjects (60.0%), including dilated
      cardiomyopathy-like damage that was more common in the left ventricular (LV)
      posterior wall. Late gadolinium enhancement on cardiac MRI was found in 5 of 6
      subjects, suggesting fibrotic cardiac muscle. In speckle tracking
      echocardiography performed seven years later, global longitudinal strain was
      decreased in these subjects, indicating LV myocardial contractile abnormality.
      These results suggest that female dystrophinopathy carriers should receive
      regular checkups for detection and treatment of cardiomyopathy, even if they have
      no cardiac symptoms.

PMID- 29358001
TI  - Catheter-based endobronchial electroporation is feasible for the focal treatment
      of peribronchial tumors.
AB  - OBJECTIVE: To evaluate the feasibility of catheter-based endobronchial
      electroporation for the treatment of peribronchial tumors and assess the
      incidence of treatment-related adverse events. METHODS: Cytotoxicity of
      electroporation with or without cisplatin or gefitinib was assessed in vitro with
      lung cancer and normal cell lines. A novel catheter was designed for
      endobronchial electroporation, and computer simulations were used to predict in
      vivo treatment effects. Electroporation with the test catheter was performed
      (2000 V, 70 pulses) in the main bronchus of 8 pigs at 11 locations. Computed
      tomography imaging was performed before they were killed at 4 hours (6 animals)
      or 4 weeks (2 animals) posttreatment. Treated airway and surrounding parenchyma
      were compared with sham treatment via gross and histopathology. RESULTS:
      Significant cell death due to electroporation and increased cytotoxicity in
      combination with cisplatin or gefitinib were observed in cancer cells only (P <
      .05). Simulations predicted penetrative electroporation of peribronchial
      parenchyma without tissue heating. Electric pulse delivery in vivo induced
      transient venous and bronchial spasms that resolved without intervention. Cross
      sectional measurement of electroporation effects on computed tomography (14.4 +/-
      1.4 by 10.5 +/- 1.3 mm) and gross pathology (17.2 +/- 3.0 by 8.8 +/- 0.6 mm) were
      representative of values predicted by simulation (P < .001). Cell death due to
      irreversible electroporation was observed in bronchial and parenchymal tissue in
      acute tissue samples. Treated lung rapidly recovered from the effects of
      electroporation without change in bronchial patency at 4 weeks posttreatment.
      CONCLUSIONS: Catheter-based endobronchial electroporation is a reproducible
      technique that can be used to treat peribronchial tumors in combination with
      cisplatin, without affecting patency of the treated bronchus.

PMID- 29358002
TI  - The effect of a natural food based tube feeding in minimizing diarrhea in
      critically ill neurological patients.
AB  - BACKGROUND & AIMS: Diarrhea has negative consequences for patients, health care
      staff and health care costs when neurological patients are fed enterally over
      long periods. We examined the effect of tube feeding with natural foods in
      reducing the number of fluid stool evacuations and diarrhea in critically ill
      neurological patients. METHODS: A multicenter, prospective, open-label and
      randomized controlled trial (RCT) was conducted at facilities in Germany
      specializing in early rehabilitation after neurological damage. Patients of the
      INTERVENTION group were fed by tube using a commercially available product based
      on real foods such as milk, meat, carrots, whereas CONTROL patients received a
      standard tube-feed made of powdered raw materials. All received enteral nutrition
      over a maximum of 30 days. The number of defecations and the consistency of each
      stool according to the Bristol Stool Chart (BSC) were monitored. In addition,
      daily calories, liquids and antibiotic-use were recorded. RESULTS: 118 Patients
      who had suffered ischemic stroke, intracerebral hemorrhage, traumatic brain
      injury or hypoxic brain damage and requiring enteral nutrition were enrolled; 59
      were randomized to receive the intervention and 59 control feed. There were no
      significant differences in clinical screening data, age, sex, observation period
      or days under enteral nutrition between the groups. Patients in both groups
      received equivalent amount of calories and fluids. In both groups antibiotics
      were frequently prescribed (69.5% in the INTERVENTION group and 75.7% in the
      CONTROL group) for 10-11 days on average. In comparison to the CONTROL group,
      patients in the INTERVENTION group had a significant reduction of the number of
      watery stool evacuations (type 7 BSC) (minus 61%, IRR = 0.39, p < 0.001). Further
      statistical evaluations using the following corrections: major diarrhea
      associated confounders (number and duration of antibiotics); shorter observation
      period of 15 days; excluding patients with Clostridiumdifficile associated
      diarrhea (CDAD) and the Per Protocol Population, confirmed the primary
      hypothesis. The number of days with diarrhea was significantly lower in the
      INTERVENTION group (0.8 +/- 1.60 days versus 2.0 +/- 3.46 days). CONCLUSIONS:
      Tube feeding with natural based food was effective in reducing the number of
      watery defecations and diarrhea in long term tube-fed critically ill neurological
      patients, compared to those fed with standard tube feeding.

PMID- 29358003
TI  - Predicting device failure after percutaneous repair of functional mitral
      regurgitation in advanced heart failure: Implications for patient selection.
AB  - BACKGROUND: Patients with heart failure (HF) and severe symptomatic functional
      mitral regurgitation (FMR) may benefit from MitraClip implantation. With
      increasing numbers of patients being treated the success of procedure becomes a
      key issue. We sought to investigate the pre-procedural predictors of device
      failure in patients with advanced HF treated with MitraClip. METHODS: From April
      2012 to November 2016, 76 patients with poor functional class (NYHA class III-IV)
      and severe left ventricular (LV) remodeling underwent MitraClip implantation at
      University Hospitals of Trieste and Bologna (Italy). Device failure was assessed
      according to MVARC criteria. Patients were subsequently followed to additionally
      assess the patient success after 12months. RESULTS: Mean age was 67+/-12years,
      the mean Log-EuroSCORE was 23.4+/-16.5%, and the mean LV end-diastolic volume
      index and ejection fraction (EF) were 112+/-33ml/m2 and 30.6+/-8.9%,
      respectively. At short-term evaluation, device failure was observed in 22 (29%)
      patients. Univariate predictors of device failure were LVEF, LV and left atrial
      volumes and anteroposterior mitral annulus diameter. Annulus dimension (OR 1.153,
      95% CI 1.002-1.327, p=0.043) and LV end-diastolic volume (OR 1.024, 95% CI 1.000
      1.049, p=0.049) were the only variables independently associated with the risk of
      device failure at the multivariate model. CONCLUSIONS: Pre-procedural
      anteroposterior mitral annulus diameter accurately predicted the risk of device
      failure after MitraClip in the setting of advanced HF. Its assessment might aid
      the selection of the best candidates to percutaneous correction of FMR.

PMID- 29358004
TI  - Hematologists' Preferences for First-line Therapy Characteristics for Multiple
      Myeloma in Japan: Attribute Rating and Discrete Choice Experiment.
AB  - PURPOSE: With the progress being made in the treatment of multiple myeloma and
      other complex cancers, a variety of clinical research and treatment options are
      being pursued. This study uses a discrete choice experiment (DCE) to estimate
      treatment characteristic preferences of hematologists in Japan. METHODS: A 2
      stage process was applied within this study. The first stage is an attribute
      rating exercise in which each of the full list of 21 attributes is rated on its
      importance by the clinicians when selecting a first-line therapy. The top 8 rated
      attributes from a stepwise logistic regression model are then used to develop a
      DCE to estimate hematologists' willingness to trade-off characteristics of the
      treatment options in their recommendation of a first-line treatment. A logit
      model was used to identify the attribute levels that were the strongest
      determinants of the physicians' treatment preferences. FINDINGS: From among the
      potential treatment attributes presented, improved overall survival had the most
      significant impact on the treatment choice of participating Japanese
      hematologists. Improvement in the ability to promptly reduce M-protein is also a
      highly prioritized treatment characteristic, with hematologists willing to
      sacrifice just over 1 month extra overall survival for this. Additionally, the
      hematologists' value improved suitability for chromosomal abnormalities with poor
      prognosis, suitability of the mechanism of action in initial treatment, and
      promptly improving calcium-renal-anemia-bone symptoms each at roughly 0.9 months
      extended overall survival. The reduction of adverse events is among the other
      significant factors in choice of treatment, though it was not found to be as
      strong a determinant as those mentioned. IMPLICATIONS: This study reinforces the
      expectation that clinical research and treatment options should continue to focus
      on overall survival and are key priorities in multiple myeloma treatment
      development. However, clinicians are willing to consider and trade off other
      clinical factors and markers in their choice of treatment. The potential
      improvements presented were also found to have a greater impact on treatment
      choice than aversion to the potential worse outcomes presented.

PMID- 29358005
TI  - Allbutt of Leeds and Duchenne de Boulogne: Newly discovered insights on Duchenne
      by a British neuropsychiatrist.
AB  - It is well-established that Guillaume-Benjamin-Amand Duchenne de Boulogne (1806
      1875), and Jean-Martin Charcot (1825-1893) were the founding fathers of Parisian
      and French neurology during the second half of the 19th century, although much
      more is known about Charcot than about his "master" Duchenne. In Britain, Thomas
      Clifford Allbutt (1836-1925) was Leeds' most distinguished physician of the 19th
      century, eventually becoming Regius Professor of Physic at Cambridge. Allbutt's
      1860-1861 year of postgraduate study in Paris and his friendship with Duchenne
      profoundly influenced his own contributions to nervous system and mental
      diseases, partly in collaboration with his colleague James Crichton-Browne (1840
      1938) at the nearby West Riding Lunatic Asylum in Wakefield, Yorkshire. The
      present report briefly recalls the careers of Duchenne and Allbutt, and also
      presents a unique account by Allbutt of Duchenne in action at the height of his
      powers, investigating and defining the previously uncharted field of
      neuromuscular diseases with the aid of his localized electrization techniques.
      This account is discussed in relation to: Duchenne's personality and pioneering
      neurological achievements; the origins of French neurology; and the development
      of Anglo-French neurological relationships during the 19th century.
      Interestingly, both Duchenne and Crichton-Browne separately made important and
      much-appreciated contributions to the third major book by Charles Darwin (1809
      1882), The Expression of the Emotions in Man and Animals, published in 1872.

PMID- 29358006
TI  - Computer-aided Design/Computer-aided Manufacturing-guided Endodontic Surgery:
      Guided Osteotomy and Apex Localization in a Mandibular Molar with a Thick Buccal
      Bone Plate.
AB  - A mandibular molar with a thick buccal bone plate is a challenging problem in
      endodontic surgery despite the increase in the success rate of endodontic surgery
      nowadays. This report describes the application of a surgical template to guide
      osteotomy and facilitate apex localization in a mandibular molar with a thick
      buccal bone plate. A 57-year-old woman visited the authors' clinic for pain in
      tooth 19 and was diagnosed with symptomatic apical periodontitis in this
      previously treated tooth. Nonsurgical retreatment was performed; however, 2 years
      later, the patient reported pain in the same tooth. A periapical lesion was
      confirmed using cone-beam computed tomographic (CBCT) imaging, and endodontic
      surgery on the mesial root of tooth 19 was planned. After CBCT imaging and cast
      scan data were transferred to implant surgical planning software, the data were
      superimposed. In the superimposed model, an anchor pin was designed to target the
      mesial root apex of tooth 19. The surgical template was then printed using a 3
      dimensional printer. Endodontic microsurgery included application of this printed
      surgical template. A computer-aided design/computer-aided manufacturing (CAD/CAM)
      guided surgical template minimized the extent of osteotomy and enabled precise
      targeting of the apex in this case. There were no postoperative complications. A
      CAD/CAM-guided surgical template is useful in endodontic surgery for complicated
      cases.

PMID- 29358007
TI  - Pretreatment with intravenous fish oil reduces hepatic ischemia reperfusion
      injury in a murine model.
AB  - BACKGROUND: Ischemia reperfusion injury is a barrier to liver surgery and
      transplantation, particularly for steatotic livers. The purpose of this study was
      to determine if pretreatment with a single dose of intravenous fish oil decreases
      hepatic ischemia reperfusion injury and improves recovery of injured livers.
      METHODS: Sixty adult male C57BL/6 mice received 1 g/kg intravenous fish oil
      (Omegaven, Fresenius Kabi) or isovolumetric 0.9% NaCl (saline) via tail vein 1
      hour before 30 minutes of 70% hepatic ischemia. Animals were killed 4, 8, or 24
      hours postreperfusion, and livers were harvested for histologic analysis.
      RESULTS: Four hours postreperfusion, saline-treated livers demonstrated marked
      ischemia diffusely around the central veins, while intravenous fish oil-treated
      livers demonstrated only patchy necrosis with intervening normal parenchyma.
      Eight hours postreperfusion, all livers demonstrated pale areas of cell loss with
      surrounding regenerating hepatocytes. Ki67 staining confirmed 14.4/10 high
      powered field (95% confidence interval, 3.2-25.6) more regenerating hepatocytes
      around areas of necrosis in intravenous fish oil-treated livers. Twenty-four
      hours postreperfusion, all livers demonstrated patchy areas of necrosis, with an
      89% (95% confidence interval, 85-92) decrease in the area of necrosis in
      intravenous fish oil-treated livers. CONCLUSION: Intravenous fish oil treatment
      prior to hepatic ischemia reperfusion injury decreased the area of hepatic
      necrosis and increased hepatocyte regeneration compared to saline treatment in a
      mouse model.

PMID- 29358009
TI  - What Can Big Data on Academic Interest Reveal about a Drug? Reflections in Three
      Major US Databases.
AB  - The different stages of the life cycle of a drug - 'prenatal' stage, birth of a
      drug, rapid growth, maturity and stability, decline, and status before 'death' -
      are reflected in the three following databases: journal articles (PubMed
      www.ncbi.nlm.nih.gov/pubmed); patents (US Patent Office
      http://partfl1.uspto.gov/netahtml/PTO/search-adv.htlm); and approved drugs (FDA -
      www.accessdata.fda.gov/scripts/cder/drugsatfda/index/cfm). These databases are
      huge, from authoritative sources, correctly classified, and they properly link
      different datasets. Analysis of such data can uncover hidden patterns important
      for the assessment of drug status and may also yield some predictions regarding
      its future prospects. Drug-related, publication-based academic bibliographic
      records are especially numerous and support the development of various
      scientometric indices. In combination with information from other types of
      databases, they can outline various trends in pharmacology. Scientometric indices
      can be classified into those indicating a change in the status of a drug, and
      those assessing the chances for success, or even drug discontinuation. Here, we
      present big data analytics on publication-based academic interest in two
      segments: (i) description of scientometric indices and (ii) their applications
      for the assessment of the status of a drug.

PMID- 29358008
TI  - An approach to value-based simulator selection: The creation and evaluation of
      the simulator value index tool.
AB  - BACKGROUND: Currently there is no reliable, standardized mechanism to support
      health care professionals during the evaluation of and procurement processes for
      simulators. A tool founded on best practices could facilitate simulator purchase
      processes. METHODS: In a 3-phase process, we identified top factors considered
      during the simulator purchase process through expert consensus (n = 127), created
      the Simulator Value Index (SVI) tool, evaluated targeted validity evidence, and
      evaluated the practical value of this SVI. A web-based survey was sent to
      simulation professionals. Participants (n = 79) used the SVI and provided
      feedback. We evaluated the practical value of 4 tool variations by calculating
      their sensitivity to predict a preferred simulator. RESULTS: Seventeen top
      factors were identified and ranked. The top 2 were technical
      stability/reliability of the simulator and customer service, with no practical
      differences in rank across institution or stakeholder role. Full SVI variations
      predicted successfully the preferred simulator with good (87%) sensitivity,
      whereas the sensitivity of variations in cost and customer service and cost and
      technical stability decreased (<=54%). The majority (73%) of participants agreed
      that the SVI was helpful at guiding simulator purchase decisions, and 88% agreed
      the SVI tool would help facilitate discussion with peers and leadership.
      CONCLUSION: Our findings indicate the SVI supports the process of simulator
      purchase using a standardized framework. Sensitivity of the tool improved when
      factors extend beyond traditionally targeted factors. We propose the tool will
      facilitate discussion amongst simulation professionals dealing with simulation,
      provide essential information for finance and procurement professionals, and
      improve the long-term value of simulation solutions. Limitations and application
      of the tool are discussed.

PMID- 29358010
TI  - Volar Plate Fixation to Treat Scaphoid Nonunion: A Case Series With Minimum 3
      Years of Follow-Up.
AB  - PURPOSE: Several options exist for treating scaphoid nonunion. For selected
      cases, some authors recommend using a volar buttress plate. The aim of the study
      was to report the clinical and radiological outcomes achieved at a minimum of 3
      years' follow-up of treating scaphoid nonunion with a scaphoid volar plate.
      METHODS: We retrospectively reviewed 15 patients with symptomatic scaphoid
      nonunion treated with scaphoid plate osteosynthesis and a bone graft from the
      volar aspect of the distal radius between January 2011 and November 2013. The
      patients' average age was 32 years (range, 21-62 years). No patient had undergone
      previous scaphoid surgery. Clinical assessments included wrist range of motion
      (ROM), grip strength, and a 10-point visual analog scale rating of pain. Further
      subjective assessment was performed using validated measurement tools. All
      patients underwent plain radiography with 6 different views and computed
      tomography before and after surgery. The scapholunate angle was measured to
      evaluate carpal alignment. RESULTS: The mean follow-up period was 42 months
      (range, 36-51 months). Bone union was obtained in 13 of 15 patients (87%) at an
      average of 5 months (range, 3-8 months) after surgery. Significant improvements
      in the scapholunate angle and visual analog scale pain score were observed.
      However, both wrist ROM and grip strength remained significantly decreased
      relative to the opposite side (62% and 55% of normal, respectively). Four
      patients experienced hardware complications: plate breakage (1 scaphoid) and
      screw back-out (3 scaphoids). Impingement between the radial styloid and the
      scaphoid plate was identified in 6 patients. Five patients required additional
      surgery to remove the plate. CONCLUSIONS: Our study indicates unsatisfactory
      results treating scaphoid nonunion with a volar scaphoid plate. Although the rate
      of union was comparable with that of other series, we noted more complications.
      We are concerned about both the high proportion of hardware complications and
      required secondary surgical procedures. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Therapeutic IV.

PMID- 29358011
TI  - From 6 years to 5 days for organ allocation policy change.

PMID- 29358012
TI  - Once- versus twice-daily dosing of eliglustat in adults with Gaucher disease type
      1: The Phase 3, randomized, double-blind EDGE trial.
AB  - Eliglustat is a first-line oral therapy for adults with Gaucher disease type 1
      (GD1) with compatible CYP2D6-metabolizer phenotypes (>90% of patients). The
      randomized, double-blind EDGE trial (NCT01074944, Sanofi Genzyme) evaluated once
      daily eliglustat dosing compared with the approved twice-daily regimen at the
      same total daily dose in adults with GD1. Subjects received twice-daily dosing
      during a 6- to 18-month lead-in period. Only subjects who attained prespecified
      treatment goals for hemoglobin, platelet count, spleen and liver volumes, and
      bone symptoms during the lead-in period were randomized to once- or twice-daily
      dosing. Of 170 enrolled patients, 156 completed the lead-in period and 131 met
      all requirements to enter the double-blind treatment period. To achieve the
      composite primary endpoint in the double-blind period, patients had to maintain
      clinical stability relative to baseline on all five endpoints (hemoglobin,
      platelet count, spleen and liver volumes, and bone symptoms) and meet
      pharmacokinetic and other tolerability requirements as determined by the
      investigator after 1year of eliglustat treatment. After 1year, 80.4% (95% CI:
      67.6, 89.8) of once-daily patients were stable compared with 83.1% (95% CI: 71.0,
      91.6) of twice-daily patients. The 95% CI for the mean difference of -2.7%
      between groups was -17.7, 11.9. Because the lower bound of the CI exceeded the
      pre-defined non-inferiority margin of -15%, once-daily dosing could not be
      declared non-inferior to twice-daily dosing. Both once-daily and twice-daily
      patients maintained mean values for hematologic and visceral measures within
      established therapeutic goals during the double-blind treatment and long-term
      extension periods. Eliglustat was generally well-tolerated during this long-term
      trial (mean treatment duration: 3.3years), with just four withdrawals (2%) for
      related adverse events (AE), and similar AE profiles for both dosing regimens.
      Patients on twice-daily eliglustat showed more stability overall, and this dose
      regimen was better tolerated, confirming the dosing regimen for most patients
      specified in the drug label.

PMID- 29358013
TI  - Perioperative Care of the Obese Cardiac Surgical Patient.
AB  - Morbid obesity is associated with impairment of cardiovascular, pulmonary,
      gastrointestinal, and renal physiology with significant perioperative
      consequences and has been linked with higher morbidity and mortality after
      cardiac surgery. Cardiac surgery patients have a higher incidence of difficult
      airway and difficult laryngoscopy than general surgery patients do, and obesity
      is associated with difficult mask ventilation and direct laryngoscopy.
      Positioning injuries occur more frequently because obese patients are at greater
      risk of pressure injury, such as rhabdomyolysis and compartment syndrome. Despite
      the association between obesity and several chronic disease states, the effects
      of obesity on perioperative outcomes are conflicting. Studies examining outcomes
      of overweight and obese patients in cardiac surgery have reported varying
      results. An "obesity paradox" has been described, in which the mortality for
      overweight and obese patients is lower compared with patients of normal weight.
      This review describes the physiologic abnormalities and clinical implications of
      obesity in cardiac surgery and summarizes recommendations for anesthesiologists
      to optimize perioperative care of the obese cardiac surgical patient.

PMID- 29358014
TI  - High Volume Aortic Practices Demonstrate Benefits Crossing Healthcare Boundaries.

PMID- 29358015
TI  - The Portuguese Registry of Hypertrophic Cardiomyopathy: Overall results.
AB  - INTRODUCTION: We report the results of the Portuguese Registry of Hypertrophic
      Cardiomyopathy, an initiative that reflects the current spectrum of cardiology
      centers throughout the territory of Portugal. METHODS: A direct invitation to
      participate was sent to cardiology departments. Baseline and outcome data were
      collected. RESULTS: A total of 29 centers participated and 1042 patients were
      recruited. Four centers recruited 49% of the patients, of whom 59% were male, and
      mean age at diagnosis was 53+/-16 years. Hypertrophic cardiomyopathy (HCM) was
      identified as familial in 33%. The major reason for diagnosis was symptoms (53%).
      HCM was obstructive in 35% of cases and genetic testing was performed in 51%.
      Invasive septal reduction therapy was offered to 8% (23% of obstructive
      patients). Most patients (84%) had an estimated five-year risk of sudden death of
      <6%. Thirteen percent received an implantable cardioverter-defibrillator. After a
      median follow-up of 3.3 years (interquartile range [P25-P75] 1.3-6.5 years), 31%
      were asymptomatic. All-cause mortality was 1.19%/year and cardiovascular
      mortality 0.65%/year. The incidence of heart failure-related death was
      0.25%/year, of sudden cardiac death 0.22%/year and of stroke-related death
      0.04%/year. Heart failure-related death plus heart transplantation occurred in
      0.27%/year and sudden cardiac death plus equivalents occurred in 0.53%/year.
      CONCLUSIONS: Contemporary HCM in Portugal is characterized by relatively advanced
      age at diagnosis, and a high proportion of invasive treatment of obstructive
      forms. Long-term mortality is low; heart failure is the most common cause of
      death followed by sudden cardiac death. However, the burden of morbidity remains
      considerable, emphasizing the need for disease-specific treatments that impact
      the natural history of the disease.

PMID- 29358016
TI  - TRIMAGE: A dedicated trimodality (PET/MR/EEG) imaging tool for schizophrenia.
AB  - Simultaneous PET/MR/EEG (Positron Emission Tomography - Magnetic Resonance -
      Electroencephalography), a new tool for the investigation of neuronal networks in
      the human brain, is presented here within the framework of the European Union
      Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use
      of cutting edge technology both in PET and in MR fields. A novel type of magnet
      (1.5T, non-cryogenic) has been built together with a PET scanner that makes use
      of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices
      (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to
      brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of
      160 mm. It enables the acquisition and assessment of molecular metabolic
      information with high spatial and temporal resolution in a given brain
      simultaneously. The dopaminergic system and the glutamatergic system in
      schizophrenic patients are investigated via PET, the same
      physiological/pathophysiological conditions with regard to functional
      connectivity, via fMRI, and its electrophysiological signature via EEG. In
      addition to basic neuroscience questions addressing neurovascular-metabolic
      coupling, this new methodology lays the foundation for individual physiological
      and pathological fingerprints for a wide research field addressing healthy aging,
      gender effects, plasticity and different psychiatric and neurological diseases.
      The preliminary performances of two components of the imaging tool (PET and MR)
      are discussed. Initial results of the search of possible candidates for suitable
      schizophrenia biomarkers are also presented as obtained with PET/MR systems
      available to the collaboration.

PMID- 29358018
TI  - Non invasive mechanical ventilation in myotonic dystrophy type 1? Hypoventilation
      versus quality of life perspective.

PMID- 29358017
TI  - Normal CA1 Place Fields but Discoordinated Network Discharge in a Fmr1-Null Mouse
      Model of Fragile X Syndrome.
AB  - Silence of FMR1 causes loss of fragile X mental retardation protein (FMRP) and
      dysregulated translation at synapses, resulting in the intellectual disability
      and autistic symptoms of fragile X syndrome (FXS). Synaptic dysfunction
      hypotheses for how intellectual disabilities like cognitive inflexibility arise
      in FXS predict impaired neural coding in the absence of FMRP. We tested the
      prediction by comparing hippocampus place cells in wild-type and FXS-model mice.
      Experience-driven CA1 synaptic function and synaptic plasticity changes are
      excessive in Fmr1-null mice, but CA1 place fields are normal. However, Fmr1-null
      discharge relationships to local field potential oscillations are abnormally
      weak, stereotyped, and homogeneous; also, discharge coordination within Fmr1-null
      place cell networks is weaker and less reliable than wild-type. Rather than
      disruption of single-cell neural codes, these findings point to invariant tuning
      of single-cell responses and inadequate discharge coordination within neural
      ensembles as a pathophysiological basis of cognitive inflexibility in FXS. VIDEO
      ABSTRACT.

PMID- 29358019
TI  - The Early Psychosis Screener (EPS): Quantitative validation against the SIPS
      using machine learning.
AB  - Machine learning techniques were used to identify highly informative early
      psychosis self-report items and to validate an early psychosis screener (EPS)
      against the Structured Interview for Psychosis-risk Syndromes (SIPS). The
      Prodromal Questionnaire-Brief Version (PQ-B) and 148 additional items were
      administered to 229 individuals being screened with the SIPS at 7 North American
      Prodrome Longitudinal Study sites and at Columbia University. Fifty individuals
      were found to have SIPS scores of 0, 1, or 2, making them clinically low risk
      (CLR) controls; 144 were classified as clinically high risk (CHR) (SIPS 3-5) and
      35 were found to have first episode psychosis (FEP) (SIPS 6). Spectral clustering
      analysis, performed on 124 of the items, yielded two cohesive item groups, the
      first mostly related to psychosis and mania, the second mostly related to
      depression, anxiety, and social and general work/school functioning. Items within
      each group were sorted according to their usefulness in distinguishing between
      CLR and CHR individuals using the Minimum Redundancy Maximum Relevance procedure.
      A receiver operating characteristic area under the curve (AUC) analysis indicated
      that maximal differentiation of CLR and CHR participants was achieved with a 26
      item solution (AUC=0.899+/-0.001). The EPS-26 outperformed the PQ-B (AUC=0.834+/
      0.001). For screening purposes, the self-report EPS-26 appeared to differentiate
      individuals who are either CLR or CHR approximately as well as the clinician
      administered SIPS. The EPS-26 may prove useful as a self-report screener and may
      lead to a decrease in the duration of untreated psychosis. A validation of the
      EPS-26 against actual conversion is underway.

PMID- 29358020
TI  - Introducing Tina Spagnola.

PMID- 29358021
TI  - Combining biochar, zeolite and wood vinegar for composting of pig manure: The
      effect on greenhouse gas emission and nitrogen conservation.
AB  - The effect of enhancing wood vinegar (WV) with a mixture of biochar (B) and
      zeolite (Z) to compost pig manure (PM) in a 130 L reactor was evaluated to
      determine the levels of greenhouse gas (GHG) and ammonia emissions. Six
      treatments were prepared in a 2:1 ratio of PM mixed with wheat straw (WS; dry
      weight basis): PM + WS (control), PM + WS + 10%B, PM + WS + 10%B + 10%Z, and PM +
      WS with 0.5%, 1.0% and 2.0%WV combined with 10%B + 10%Z. These were composted for
      50 days, and the results indicated that the combined use of B, Z, and WV could
      shorten the thermophilic phase and improve the maturity of compost compared to
      the control treatment. In addition, WV mixed with B and Z could reduce ammonia
      loss by 64.45-74.32% and decrease CO2, CH4, and N2O emissions by 33.90-46.98%,
      50.39-61.15%, and 79.51-81.10%, respectively. Furthermore, compared to treatments
      in which B and B + Z were added, adding WV was more efficient to reduce the
      nitrogen and carbon loss, and the 10%B + 10%Z + 2%WV treatment presented the
      lowest loss of carbon (9.16%) and nitrogen (0.75%). Based on the maturity indexes
      used, nitrogen conservation, and efficiency of GHG emissions reduction, the
      treatment 10%B + 10%Z + 2%WV is suggested for efficient PM composting.

PMID- 29358022
TI  - Innovative dual-step management of semi-aerobic landfill in a tropical climate.
AB  - Despite concerted efforts to innovate the solid waste management (SWM) system,
      land disposal continues to represent the most widely used technology in the
      treatment of urban solid waste worldwide. On the other hand, landfilling is an
      unavoidable step in closing the material cycle, since final residues, although
      minimized, need to be safely disposed of and confined. In recent years, the
      implementation of more sustainable landfilling aims to achieve the Final Storage
      Quality conditions as fast as possible. In particular, semi-aerobic landfill
      appears to represent an effective solution for use in the poorest economies due
      to lower management costs and shorter aftercare resulting from aerobic
      stabilisation of the waste. Nevertheless, the implementation of a semi-aerobic
      landfill in a tropical climate may affect the correct functioning of the plant: a
      lack of moisture during the dry season and heavy rainfalls during the wet season
      could negatively affect performance of both the degradation process, and of
      leachate and biogas management. This paper illustrates the results obtained
      through the experimentation of a potential dual-step management of semi-aerobic
      landfilling in a tropical climate in which composting process was reproduced
      during the dry season and subsequently flushing (high rainfall rate) during the
      wet period. Eight bioreactors specifically designed: four operated under
      anaerobic conditions and four under semi-aerobic conditions; half of the reactors
      were filled with high organic content waste, half with residual waste obtained
      following enhanced source segregation. The synergic effect of the subsequent
      phases (composting and flushing) in the semi-aerobic landfill was evaluated on
      the basis of both types of waste. Biogas production, leachate composition and
      waste stabilization were analysed during the trial and at the end of each step,
      and compared in view of the performance of anaerobic reactors. The results
      obtained underlined the effectiveness of the dual-step management evidencing how
      wastes reached a higher degree of stabilization and reference FSQ values for
      leachate were achieved over a one-year simulation period.

PMID- 29358023
TI  - Surgical strategy and outcomes for the delayed diagnosis of pulmonary atresia
      with intact ventricular septum.
AB  - BACKGROUND: In the present study, we summarize the experiences and evaluate
      clinical outcomes for the delayed diagnosis of pulmonary atresia with intact
      ventricular septum (PAIVS) patients when undergoing an initial visit and
      diagnosis in our heart center. METHODS: Fifty-eight cases of delayed diagnosis of
      PAIVS in patients aged more than 6 months between January 2006 and June 2016 were
      reviewed in our hospital. The median age at initial diagnosis was 12.2 months
      (range, 6.1-79.6 months). Forty-five cases eventually reached definitive repair.
      Survival, risk factors for death, and clinical status after definitive repair
      were assessed. RESULTS: Among patients who completed definitive repair, the
      Fontan procedure was performed in a large proportion of older PAIVS children
      (42.2%, 19/45), while only a few patients received biventricular repair (22.2%,
      10/45). The medium-term (10-year) survival rates of biventricular repair, 1.5
      ventricular repair, and univentricular palliation were 100.0%, 93.3%, and 81.2%,
      respectively. At the latest follow-up, most patients had a good clinical status
      after definitive repairs, with a low re-operation rate. CONCLUSIONS: A large
      proportion of the delayed diagnosis of PAIVS patients had to receive
      univentricular palliation because of limited potential for right ventricular
      growth. However, optimal definitive repairs could also have been achieved in
      these patients with a low mortality rate.

PMID- 29358024
TI  - The association between relevant co-morbidities and prevalent as well as incident
      heart failure in patients with atrial fibrillation.
AB  - BACKGROUND: Congestive heart failure (CHF) is a serious complication in patients
      with atrial fibrillation (AF). OBJECTIVE: To study associations between relevant
      co-morbidities and CHF in patients with AF. METHODS: Study population included
      all adults (n=12,283) >=45 years diagnosed with AF at 75 primary care centers in
      Sweden 2001-2007. Logistic regression was used to calculate odds ratios with 95%
      confidence intervals (CIs) for the associations between co-morbidities, and
      prevalent CHF. In a subsample (n=9424), (excluding patients with earlier CHF),
      Cox regression was used to estimate hazard ratios with 95% CIs for the
      association between co-morbidities, and a first hospital diagnosis of CHF, after
      adjustment for age and socio-economic factors. RESULTS: During 5.4 years' follow
      up (standard deviation 2.5), 2259 patients (24.0%; 1135 men, 21.8%, and 1124
      women, 26.7%) were diagnosed with CHF. Patients with hypertension were less
      likely to have CHF, while a diagnosis of coronary heart disease, valvular heart
      disease, diabetes, or chronic obstructive pulmonary disease (COPD), was
      consistently associated with CHF among men and women. CHF was more common among
      women with depression. The relative fully adjusted risk of incident CHF was
      increased for the following diseases in men with AF: valvular heart disease,
      cardiomyopathy, and diabetes; and for the following diseases in women: valvular
      heart disease, diabetes, obesity, and COPD. The corresponding risk was decreased
      among women for hypertension. CONCLUSIONS: In this clinical setting we found
      hypertension to be associated with a decreased risk of CHF among women; valvular
      heart disease and diabetes to be associated with an increased risk of CHF in both
      sexes; and cardiomyopathy to be associated with an increased risk of CHF among
      men.

PMID- 29358025
TI  - Chain Assembly and Disassembly Processes Differently Affect the Conformational
      Space of Ubiquitin Chains.
AB  - Ubiquitination is the most versatile posttranslational modification. The
      information is encoded by linkage type as well as chain length, which are
      translated by ubiquitin binding domains into specific signaling events. Chain
      topology determines the conformational space of a ubiquitin chain and adds an
      additional regulatory layer to this ubiquitin code. In particular, processes that
      modify chain length will be affected by chain conformations as they require
      access to the elongation or cleavage sites. We investigated conformational
      distributions in the context of chain elongation and disassembly using pulsed
      electron-electron double resonance spectroscopy in combination with molecular
      modeling. Analysis of the conformational space of diubiquitin revealed
      conformational selection or remodeling as mechanisms for chain recognition during
      elongation or hydrolysis, respectively. Chain elongation to tetraubiquitin
      increases the sampled conformational space, suggesting that a high intrinsic
      flexibility of K48-linked chains may contribute to efficient proteasomal
      degradation.

PMID- 29358026
TI  - Regulation of Kinase Activity in the Caenorhabditis elegans EGF Receptor, LET-23.
AB  - In the active HER receptor dimers, kinases play distinct roles; one is the
      catalytically active kinase and the other is its allosteric activator. This
      specialization enables signaling by the catalytically inactive HER3, which
      functions exclusively as an allosteric activator upon heterodimerization with
      other HER receptors. It is unclear whether the allosteric activation mechanism
      evolved before HER receptors functionally specialized. We determined the crystal
      structure of the kinase domain of the only EGF receptor in Caenorhabditis
      elegans, LET-23. Our structure of a non-human EGFR kinase reveals autoinhibitory
      features conserved in the human counterpart. Strikingly, mutations within the
      putative allosteric dimer interface abrogate activity of the isolated LET-23
      kinase and of the full-length receptor despite these regions being only partially
      conserved with human EGFR. Our results indicate that ancestral EGFRs have built
      in features that poise them for allosteric activation that could facilitate
      emergence of the catalytically dead, yet functional, orthologs.

PMID- 29358028
TI  - Personality and Parkinson's disease: A meta-analysis.
AB  - INTRODUCTION: Personality changes are considered pre-motor features of
      Parkinson's disease (PD). Cross-sectional studies revealed that PD patients were
      more introvert, apprehensive, and cautious than healthy subjects (HS), whereas
      other studies failed to disclose these behavioural traits. Some studies found
      mixed results concerning Novelty Seeking (NS) and Harm Avoidance (HA) profiles in
      PD patients. To better clarify the personality profile in PD we performed a meta
      analysis on studies exploring such topic according to both Cloninger's
      Psychobiological Model (PM) and Big Five Model (BFM) METHODS: The meta-analysis
      included 17 studies evaluating the personality in PD patients compared with HS.
      The outcomes were the dimensions of the temperament and character of the PM and
      personality traits of BFM. Effect sizes from data reported in the primary studies
      were computed using Hedges'g unbiased approach. Heterogeneity among the studies
      and publication bias were assessed. Meta-regressions were conducted with age at
      evaluation, gender, schooling, and type of personality trait tools as moderators.
      RESULTS: As for PM, PD patients scored higher on HA and lower on NS than HS. No
      difference was found on Reward Dependence, Perseverance/Persistence and on
      character level. As for BFM, higher levels of Neuroticism, but lower levels of
      Openness and Extraversion were associated with PD. DISCUSSION: The personality
      profile in PD is characterized by high Neuroticism and HA, and by low Openness,
      Extraversion and NS. The personality profile delineated in the present study on
      PD patients seems to reflect the premorbid one and might contribute to
      development and persistence of affective disorders.

PMID- 29358029
TI  - [Do you speak English? Yes, we do!]

PMID- 29358027
TI  - Design, synthesis and biological evaluation of new carbazole derivatives as anti
      cancer and anti-migratory agents.
AB  - Based on the efficacy of EHop-016 as an inhibitor of migration and Rac1
      activation, a new series of carbazole derivatives has been synthesized. Cytotoxic
      and anti-migratory effects of these compounds were evaluated in MCF-7 and MDA-MB
      231 breast cancer cell lines. Preliminary investigations of their anticancer
      activity demonstrated that several compounds have moderate antiproliferative
      effects on cancer cell lines with GI50 values in the range of 13-50 uM.
      Furthermore, compounds 3b and 11b inhibit migration activity of metastatic cell
      line MDA-MB-231 by 32% and 34%, respectively. Compound 11b was shown to inhibit
      activation of the Rho GTPase Rac1 by 55% at 250 nM in both MDA-MB-231 and MDA-MB
      435 cell lines. Compared with the IC50 of Rac1 inhibition by lead compound EHop
      016 of 1.1 uM, compound 11b demonstrates 4X improved in vitro efficacy.

PMID- 29358030
TI  - The future of pharmacy practice research - Perspectives of academics and
      practitioners from Australia, NZ, United Kingdom, Canada and USA.
AB  - BACKGROUND: Healthcare is under significant pressure with the explosion of long
      term conditions, shift in worldwide demographics and is evolving through advances
      in technology. Aligned with this is the changing role of pharmacy from the
      traditional dispenser of medicines to having (in addition) a more advanced
      clinical role. This study aimed to understand what the pharmacy practice research
      agenda might look like from the viewpoint of pharmacy academics and practitioners
      across five high-income countries. METHOD: Qualitative methods were used, and
      thirty one-hour interviews were undertaken with practitioners and academics from
      five economically advanced countries. These nations have comparable socio
      economic status but differing health systems and include; Australia, Canada, New
      Zealand, United Kingdom and United States of America. Six key informants were
      chosen from each country, three academics and three community pharmacists. A
      general inductive analysis was undertaken to analyse the most common and
      recurring themes. RESULTS: These themes of research were based around current
      community pharmacy practice issues and the enablers to changing the profession.
      Specific areas pharmacy practice could be more involved with included long term
      health conditions. Some community pharmacists also believed that research into
      the impact of professional standards and policy change would be beneficial. The
      findings of this research suggest that current pharmacy practice research methods
      are sufficient, but need to be used more effectively. CONCLUSION: Participants
      identified a wide range of issues within community pharmacy practice. Academics
      largely focused on how research can be utilised in the community and how to
      implement findings to ensure sustainability of pharmacy practice research. Issues
      that community pharmacists would like to research are related to the current
      practice model, such as allocating time to provide patient-focused services in
      addition to managing a business.

PMID- 29358031
TI  - Effect of Prophylactic Cranial Irradiation on Overall Survival in Metastatic
      Small-Cell Lung Cancer: A Propensity Score-Matched Analysis.
AB  - INTRODUCTION: Patients with small-cell lung cancer (SCLC) have a high incidence
      of occult brain metastases and are often treated with prophylactic cranial
      irradiation (PCI). Despite a small survival advantage in some studies, the role
      of PCI in extensive stage SCLC remains controversial. We used the National Cancer
      Database to assess survival of patients with metastatic SCLC treated with PCI.
      PATIENTS AND METHODS: Metastatic SCLC patients without brain metastases were
      identified. To minimize treatment selection bias, patients with an overall
      survival (OS) < 6 months were excluded. Cox regression identified variables
      associated with OS. Patients were propensity score-matched on factors associated
      with receipt of PCI or OS. The effect of PCI on OS was examined using Kaplan
      Meier estimates. RESULTS: In the overall cohort (n = 4257), treatment with PCI (n
      = 473) was associated with improved survival (hazard ratio, 0.66; 95% confidence
      interval, 0.60-0.74; P < .0001). Comparisons of propensity score-matched cohorts
      revealed a significant survival benefit for patients who received PCI in median
      OS (13.9 vs. 11.1 months; P < .0001), as well as 1- and 2-year OS (61.2% vs.
      44.0% and 19.8% vs. 11.5%, respectively; P < .0001). This survival benefit
      persisted even after excluding patients who survived < 9 months (median: 15.3 vs.
      12.9 months; P < .0001). In multivariable analysis, predictors of receipt of PCI
      were Caucasian race, younger age, and lower Charlson-Deyo score. CONCLUSION:
      Using a modern population-based data set, we showed that metastatic SCLC patients
      treated with PCI have significantly improved OS. This large retrospective study
      helps address the conflicting prospective data.

PMID- 29358032
TI  - Spring assisted cranioplasty: A patient specific computational model.
AB  - Implantation of spring-like distractors in the treatment of sagittal
      craniosynostosis is a novel technique that has proven functionally and
      aesthetically effective in correcting skull deformities; however, final shape
      outcomes remain moderately unpredictable due to an incomplete understanding of
      the skull-distractor interaction. The aim of this study was to create a patient
      specific computational model of spring assisted cranioplasty (SAC) that can help
      predict the individual overall final head shape. Pre-operative computed
      tomography images of a SAC patient were processed to extract a 3D model of the
      infant skull anatomy and simulate spring implantation. The distractors were
      modeled based on mechanical experimental data. Viscoelastic bone properties from
      the literature were tuned using the specific patient procedural information
      recorded during surgery and from x-ray measurements at follow-up. The model
      accurately captured spring expansion on-table (within 9% of the measured values),
      as well as at first and second follow-ups (within 8% of the measured values).
      Comparison between immediate post-operative 3D head scanning and numerical
      results for this patient proved that the model could successfully predict the
      final overall head shape. This preliminary work showed the potential application
      of computational modeling to study SAC, to support pre-operative planning and
      guide novel distractor design.

PMID- 29358033
TI  - Response from the Editors: time-lapse systems for ART - meta-analyses and the
      issue of bias.

PMID- 29358034
TI  - The effects of a school-based exercise program on neurophysiological indices of
      working memory operations in adolescents.
AB  - OBJECTIVES: To examine the effects of a structured exercise program implemented
      during school break-time on working memory maintenance and neurophysiological
      indices of task preparation processes in adolescents. DESIGN: Using class-wise
      random allocation, participants from four classes were divided into an exercise
      (n=20) and a wait-list control group (n=16). Over a period of eight weeks, the
      exercise group engaged in 20min of combined aerobic and coordinative exercise on
      each school day. METHODS: Prior to and after the intervention period,
      participants performed a computer-based Sternberg task for the assessment of
      working memory performance. Simultaneously, the contingent negative variation
      (CNV) of event-related potentials was measured. RESULTS: The exercise group
      demonstrated a larger decrease in reaction time from pre- to post-test relative
      to the control group, F(1, 31)=13.5, p<0.001. No changes were found for accuracy
      on the Sternberg task across groups. Using cluster-based permutation testing, the
      analysis of event-related potentials revealed a significant increase of the
      initial CNV from pre- to post-test in the exercise group, cluster value=-2376.2,
      p=0.006, which was most pronounced for the fronto-central region, with no such
      effect observed for the control group. CONCLUSIONS: Daily engagement in a short
      combined aerobic and coordinative exercise program following the school lunch
      time break elicits benefits for working memory in adolescents. These changes are
      accompanied by improvements of task preparation processes, which allow the
      selection of a more appropriate cognitive control strategy.

PMID- 29358035
TI  - EWS/FLI Confers Tumor Cell Synthetic Lethality to CDK12 Inhibition in Ewing
      Sarcoma.
AB  - Many cancer types are driven by oncogenic transcription factors that have been
      difficult to drug. Transcriptional inhibitors, however, may offer inroads into
      targeting these cancers. Through chemical genomics screening, we identified that
      Ewing sarcoma is a disease with preferential sensitivity to THZ1, a covalent
      small-molecule CDK7/12/13 inhibitor. The selective CDK12/13 inhibitor, THZ531,
      impairs DNA damage repair in an EWS/FLI-dependent manner, supporting a synthetic
      lethal relationship between response to THZ1/THZ531 and EWS/FLI expression. The
      combination of these molecules with PARP inhibitors showed striking synergy in
      cell viability and DNA damage assays in vitro and in multiple models of Ewing
      sarcoma, including a PDX, in vivo without hematopoietic toxicity.

PMID- 29358036
TI  - Descriptive epidemiology of metabolic syndrome among obese adolescent population.
AB  - AIMS: The study was done to assess the magnitude of problems of metabolic
      syndrome among obese adolescents. MATERIALS AND METHOD: It was a cross-sectional
      study done from January 2013 to June 2014 in paediatric endocrine outpatient
      department in BIRDEM General Hospital, Dhaka, Bangladesh. Total 172 adolescents
      having exogenous obesity aged 10-18 years were included. Impaired fasting glucose
      (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) were
      defined as per WHO criteria.The adolescents having Body Mass Index (BMI) >=95th
      centile were classified as obese.Waist circumference was measured at the level
      midway between the lower rib margin & the iliac crest, at the level of umbilicus
      with the person breathing out gently in centimeter. Hip circumference was
      measured at the maximum width over the buttocks at the level of the greater
      trochanters in centimeter. RESULT: Among 172 obese adolescents, metabolic
      syndrome was found in 66 patients (38.4%). The commonest metabolic abnormality
      among those having metabolic syndrome was low HDL level (77.3%) followed by high
      triglyceride level(71.2%). Glucose intolerance (IFG and/or IGT) was found in
      16.7%, Type 2 DM in 10.6%, systolic hypertension in 10.7% and diastolic
      hypertension in 12.1%. Triglyceride (p = 0.042) and Cholesterol level (p = 0.016)
      were significantly higher and HDL-cholesterol level (p = 0.000) was significantly
      lower among obese adolescents having metabolic syndrome. Less physical activity
      (p = 0.04) was significantly related to the development of metabolic syndrome. On
      logistic regression analysis male sex, family history of obesity and low HDL
      cholesterol correlated to metabolic syndrome. CONCLUSION: The High rate of
      metabolic syndrome among obese adolescents is alarming.

PMID- 29358037
TI  - Antidepressant-Induced Activation in Children and Adolescents: Risk, Recognition
      and Management.
AB  - The tolerability of antidepressants is poorly characterized in children and
      adolescents with depressive and anxiety disorders. Among adverse events that
      affect the tolerability of antidepressants in youth is activation, a cluster of
      symptoms that represent a hyperarousal event characterized by impulsivity,
      restlessness, and/or insomnia. This cluster of symptoms was first identified as a
      side effect of selective serotonin and selective serotonin norepinephrine
      inhibitors (SSRIs and SSNRIs) in the early 1990s; however, activation remains
      poorly characterized in terms of prevalence, risk factors, and pathophysiology.
      This article describes the pathophysiology of antidepressant-related activation,
      predictors of activation and its clinical management in youth with depressive and
      anxiety disorders who are treated with antidepressant medications.

PMID- 29358038
TI  - Comprehensive analysis of mRNA internal cleavage sites in Arabidopsis thaliana.
AB  - The major obstacle of efficient transgene expression seems to be gene silencing,
      and one of the important factors in gene silencing is mRNA stability. Regulation
      of mRNA stability is an important aspect of the control of gene expression. mRNAs
      are degraded by both exonucleolytic digestion and endonucleolytic cleavage.
      However, with the exception of small RNA-guided cleavage, the mechanisms
      underlying endonucleolytic cleavage-dependent RNA degradation remain to be
      elucidated. High-throughput approaches for genome-wide profiling of RNA cleavage
      sites, collectively termed degradome sequencing, have been developed by several
      groups. These analyses have contributed to the identification of mRNA cleavage
      sites in plants, but due to selection of poly (A) mRNA in library preparation,
      these approaches cannot identify cleavage sites in a fully accurate manner. To
      address this issue, we developed a new experimental method, truncated RNA end
      sequencing (TREseq), which enabled us to accurately identify many cleavage sites.
      TREseq can also be used to estimate the efficiency of mRNA cleavage, revealing
      differences in base frequencies near cleavage sites that reflect differences in
      cleavage efficiency. These results will contribute to gain important knowledge
      about the stability of the transgene mRNA in the future.

PMID- 29358040
TI  - Collaborate or Collapse: Capacity Building in Zoonotic and Neglected Tropical
      Disease Modelling.
AB  - We share the insights from a successful collaboration in organizing and
      implementing an international scientific capacity-building workshop in Malaysia
      titled Mathematical Modelling of Neglected Infectious Diseases: Capacity Building
      in Southeast Asia. This workshop focused on the delivery of technical know-how
      and on essential soft skills related to effective grant proposal writing and
      networking.

PMID- 29358039
TI  - Essential Role of Nr2f Nuclear Receptors in Patterning the Vertebrate Upper Jaw.
AB  - The jaw is central to the extensive variety of feeding and predatory behaviors
      across vertebrates. The bones of the lower but not upper jaw form around an early
      developing cartilage template. Whereas Endothelin1 patterns the lower jaw, the
      factors that specify upper-jaw morphology remain elusive. Here, we identify
      Nuclear Receptor 2f genes (Nr2fs) as enriched in and required for upper-jaw
      formation in zebrafish. Combinatorial loss of Nr2fs transforms maxillary
      components of the upper jaw into lower-jaw-like structures. Conversely, nr2f5
      misexpression disrupts lower-jaw development. Genome-wide analyses reveal that
      Nr2fs repress mandibular gene expression and early chondrogenesis in maxillary
      precursors. Rescue of lower-jaw defects in endothelin1 mutants by reducing Nr2f
      dosage further demonstrates that Nr2f expression must be suppressed for normal
      lower-jaw development. We propose that Nr2fs shape the upper jaw by protecting
      maxillary progenitors from early chondrogenesis, thus preserving cells for later
      osteogenesis.

PMID- 29358041
TI  - The RNA-Binding Protein NONO Coordinates Hepatic Adaptation to Feeding.
AB  - The mechanisms by which feeding and fasting drive rhythmic gene expression for
      physiological adaptation to daily rhythm in nutrient availability are not well
      understood. Here we show that, upon feeding, the RNA-binding protein NONO
      accumulates within speckle-like structures in liver cell nuclei. Combining RNA
      immunoprecipitation and sequencing (RIP-seq), we find that an increased number of
      RNAs are bound by NONO after feeding. We further show that NONO binds and
      regulates the rhythmicity of genes involved in nutrient metabolism post
      transcriptionally. Finally, we show that disrupted rhythmicity of NONO target
      genes has profound metabolic impact. Indeed, NONO-deficient mice exhibit impaired
      glucose tolerance and lower hepatic glycogen and lipids. Accordingly, these mice
      shift from glucose storage to fat oxidation, and therefore remain lean throughout
      adulthood. In conclusion, our study demonstrates that NONO post-transcriptionally
      coordinates circadian mRNA expression of metabolic genes with the feeding/fasting
      cycle, thereby playing a critical role in energy homeostasis.

PMID- 29358042
TI  - Determinants of high device cost in current percutaneous coronary interventions.
AB  - BACKGROUND: Percutaneous coronary interventions (PCI), especially medical
      devices, consume large amounts of medical resources. It is important to know
      which type of lesions requires high device costs among current PCI. The purpose
      of this study was to investigate the association between lesion characteristics
      and medical device costs in current PCI. METHODS: We identified 593 coronary
      artery lesions in our PCI database between January 1, 2015 and December 31, 2015.
      The total PCI cost was calculated for each lesion. The highest quartile (Q1) of
      total PCI costs was defined as the highest cost group, whereas the other
      quartiles (Q2, Q3, Q4) were defined as the low-intermediate cost group. RESULTS:
      The mean PCI cost in the highest cost and low-intermediate cost groups was
      Y1,032,943 +/- 211,912 and Y532,547 +/- 112,127, respectively. In a multivariate
      logistic regression analysis, lesion length (10 mm increase: OR 2.93, 95% CI 2.25
      3.82, P < 0.001), left main lesion (OR 2.96, 95% CI 1.02-8.60, P = 0.046),
      moderate to severe calcification (OR 16.43, 95% CI 7.97-33.88, P < 0.001),
      chronic total occlusion (CTO) (OR 5.83, 95% CI 2.07-16.39, P = 0.001), and
      bifurcation (OR 2.01, 95% CI 1.08-3.75, P = 0.027) were significantly associated
      with the highest cost group. CONCLUSIONS: Lesion characteristics including CTO,
      diffuse long lesion, calcification, and bifurcation were significantly associated
      with the highest device cost. Non-CTO complex lesions including bifurcation and
      calcification as well as CTO lesions require higher PCI device costs than non
      complex lesions.

PMID- 29358043
TI  - Impact of Acute Kidney Injury on Short- and Long-term Outcomes After
      Transcatheter Aortic Valve Implantation.
AB  - INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is frequently observed
      after transcatheter aortic valve implantation (TAVI) and is associated with
      higher mortality. However, the impact of AKI on long-term outcomes remains
      controversial. Therefore, we sought to evaluate the impact of AKI on short- and
      long-term outcomes following TAVI using the Valve Academic Research Consortium 2
      criteria. METHODS: Consecutive patients (n = 794) with severe aortic stenosis who
      underwent TAVI were included in a multicenter Brazilian registry. Logistic
      regression analysis was used to identify predictors of AKI. Four-year outcomes
      were determined as Kaplan-Meier survival curves, and an adjusted landmark
      analysis was used to test the impact of AKI on mortality among survivors at 12
      months. RESULTS: The incidence of AKI after TAVI was 18%. Independent predictors
      of AKI were age, diabetes mellitus, major or life-threatening bleeding and valve
      malpositioning. Acute kidney injury was independently associated with higher risk
      of all-cause death (adjusted HR, 2.8; 95%CI, 2.0-3.9; P < .001) and
      cardiovascular mortality (adjusted HR, 2.9; 95%CI, 1.9-4.4; P < .001) over the
      entire follow-up period. However, when considering only survivors at 12 months,
      there was no difference in both clinical endpoints (adjusted HR, 1.2; 95%CI, 0.5
      2.4; P = .71, and HR, 0.7; 95%CI, 0.2-2.1; P = .57, respectively). CONCLUSIONS:
      Acute kidney injury is a frequent complication after TAVI. Older age, diabetes,
      major or life-threatening bleeding, and valve malpositioning were independent
      predictors of AKI. Acute kidney injury is associated with worse short- and long
      term outcomes. However, the major impact of AKI on mortality is limited to the
      first year after TAVI.

PMID- 29358044
TI  - CRISPR-Based Chromatin Remodeling of the Endogenous Oct4 or Sox2 Locus Enables
      Reprogramming to Pluripotency.
AB  - Generation of induced pluripotent stem cells typically requires the ectopic
      expression of transcription factors to reactivate the pluripotency network.
      However, it remains largely unclear what remodeling events on endogenous
      chromatin trigger reprogramming toward induced pluripotent stem cells (iPSCs).
      Toward this end, we employed CRISPR activation to precisely target and remodel
      endogenous gene loci of Oct4 and Sox2. Interestingly, we found that single-locus
      targeting of Sox2 was sufficient to remodel and activate Sox2, which was followed
      by the induction of other pluripotent genes and establishment of the pluripotency
      network. Simultaneous remodeling of the Oct4 promoter and enhancer also triggered
      reprogramming. Authentic pluripotent cell lines were established in both cases.
      Finally, we showed that targeted manipulation of histone acetylation at the Oct4
      gene locus could also initiate reprogramming. Our study generated authentic iPSCs
      with CRISPR activation through precise epigenetic remodeling of endogenous loci
      and shed light on how targeted chromatin remodeling triggers pluripotency
      induction.

PMID- 29358045
TI  - Consolidation Radiation Therapy for Patients With Advanced Hodgkin Lymphoma in
      Complete Metabolic Response According to PET-CT or Gallium Imaging.
AB  - INTRODUCTION: The purpose of this study was to evaluate the role of consolidation
      radiation therapy (RT) in advanced Hodgkin lymphoma (HL) in the setting of a
      complete metabolic response (CR) to chemotherapy (ChT). PATIENTS AND METHODS:
      Patients with stage III/IV HL treated with ChT alone or combined modality therapy
      (CMT) between 1992 and 2012 were reviewed. Only patients in a CR according to
      positron emission tomography-computed tomography (PET-CT) or gallium imaging were
      included. Clinical end points were estimated using the Kaplan-Meier method and a
      multivariate analysis using the Cox proportional hazards model was performed.
      RESULTS: Ninety patients were identified (46 CMT; 44 ChT alone). Median follow-up
      was 50 months. ChT (median 6 cycles) consisted primarily of ABVD (doxorubicin,
      bleomycin, vinblastine, and dacarbazine; 74%) or an ABVD hybrid (10%). Post-ChT
      imaging consisted of PET-CT (71%) or gallium (29%). RT plans primarily included
      all initially involved sites of disease with a median dose of 21 Gy (range, 13-31
      Gy). CMT was associated with improved 5-year progression-free survival (PFS; 88%
      vs. 65%, respectively; P < .001) and overall survival (97% vs. 78%, respectively;
      P = .002) compared with ChT alone. In multivariate analysis, age younger than 45
      years (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.07-0.74; P =
      .013) and CMT (HR, 0.32; 95% CI, 0.11-0.96; P = .04) were independently
      associated with improved PFS. Secondary malignancies were comparable in both
      cohorts (5 with CMT, 4 with ChT), whereas cardiac events were slightly more
      frequent with CMT (5 vs. 2). CONCLUSION: Low-dose RT, administered to all sites
      of original involvement, was associated with improved PFS, even in the setting of
      a metabolic CR after ABVD.

PMID- 29358046
TI  - Clinical course of a cohort with type 2 diabetes mellitus after endocrine
      assessment. A 26-week study.
AB  - OBJECTIVE: To assess the degree of metabolic control and hypoglycemic treatments
      in a cohort of patients with type 2 diabetes mellitus (T2DM) after evaluation in
      an endocrinology clinic. MATERIAL AND METHODS: A prospective cohort study on 465
      patients with T2DM who were not being monitored at an endocrinology clinic. Blood
      glucose control data and treatments received were recorded at an initial visit
      and after 26 weeks of follow-up. RESULTS: Baseline glycosylated hemoglobin
      (HbA1c) level was 8.3+/-1.8%, as compared to 6.6+/-0.9% after 26 weeks of follow
      up (P<.0001). The proportion of patients with HbA1c levels <7% increased from
      33.1% to 71.3% (P<.0001). In 59.9% of patients, a decrease >=0.8% in HbA1c was
      seen. In the multivariate analysis, variables predicting for an improvement in
      the degree of metabolic control were older age (OR 1.038; 95%CI 1-1.07; P=.041),
      higher baseline HbA1c values (OR 5.51; 95%CI 3.4-9; P<.0001), T2DM duration <5
      years (OR 4.63; 95%CI 1.6-13.3; P=.005), and change in hypoglycemic treatment (OR
      2.77, 95%CI 1.1-6.9; P=.03). Hypoglycemic therapy was changed in 75.1% of study
      patients with T2DM. After 26 weeks of follow-up, decreases were seen in both the
      proportion of patients who receiveding no treatment (from 7% to 0.3%, P<.0001)
      and the proportions of patients on oral antidiabetic therapy (60.9% vs 55.5%,
      P=.003) and insulin (10.5% vs 6.2%, P=.021). However, the proportion of patients
      receiving insulin combined with oral antidiabetic drugs increased from 21.1% to
      38% (P<.0001). CONCLUSIONS: An improved metabolic control was seen in this cohort
      of patients with T2DM after their evaluation in an endocrinology clinic. However,
      HbA1c levels <7% were not achieved in 28.7% of patients, which shows the
      difficulty to achieve adequate control in clinical practice.

PMID- 29358047
TI  - Teachers' attitudes and perceptions about preparation of public schools to assist
      students with type 1 diabetes.
AB  - OBJECTIVE: To assess teachers' attitudes and perceptions about preparation of
      public primary and secondary education schools in the Puerto Real University
      Hospital (Cadiz, Spain) area to care for students with type 1 diabetes mellitus
      (T1DM) METHODS: A descriptive observational study where answers to an attitude
      and perception questionnaire on the preparation of schools to care for pupils
      with T1DM were analyzed. A total of 765 teachers (mean age, 44.3+/-8.8 years;
      61.7% women) from 44 public schools in the area of the Puerto Real University
      Hospital were selected by random sampling. RESULTS: Overall, 43.2% of teachers
      surveyed had or had previously had students with T1DM, but only 0.8% had received
      specific training on diabetes. 18.9% of teachers reported that one of their
      students with T1DM had experienced at least one episode of hypoglycemia at
      school, and half of them felt that their school was not prepared to deal with
      diabetic emergencies. 6.4% stated that their school had glucagon in its first aid
      kit, and 46.9% would be willing to administer it personally. Women, physical
      education teachers, and headmasters had a more positive perception of the school
      than their colleagues. Teachers with a positive perception of school preparation
      and with a positive attitude to administer glucagon were significantly younger
      than those with no positive perception and attitude. CONCLUSIONS: The study
      results suggest that teachers of public schools in our health area have not been
      specifically trained in the care of patients with T1DM and perceive that their
      educational centers are not qualified to address diabetic emergencies.

PMID- 29358048
TI  - Establishment of DNA-DNA Interactions by the Cohesin Ring.
AB  - The ring-shaped structural maintenance of chromosome (SMC) complexes are multi
      subunit ATPases that topologically encircle DNA. SMC rings make vital
      contributions to numerous chromosomal functions, including mitotic chromosome
      condensation, sister chromatid cohesion, DNA repair, and transcriptional
      regulation. They are thought to do so by establishing interactions between more
      than one DNA. Here, we demonstrate DNA-DNA tethering by the purified fission
      yeast cohesin complex. DNA-bound cohesin efficiently and topologically captures a
      second DNA, but only if that is single-stranded DNA (ssDNA). Like initial double
      stranded DNA (dsDNA) embrace, second ssDNA capture is ATP-dependent, and it
      strictly requires the cohesin loader complex. Second-ssDNA capture is relatively
      labile but is converted into stable dsDNA-dsDNA cohesion through DNA synthesis.
      Our study illustrates second-DNA capture by an SMC complex and provides a
      molecular model for the establishment of sister chromatid cohesion.

PMID- 29358049
TI  - Ultraconserved Enhancers Are Required for Normal Development.
AB  - Non-coding "ultraconserved" regions containing hundreds of consecutive bases of
      perfect sequence conservation across mammalian genomes can function as distant
      acting enhancers. However, initial deletion studies in mice revealed that loss of
      such extraordinarily constrained sequences had no immediate impact on viability.
      Here, we show that ultraconserved enhancers are required for normal development.
      Focusing on some of the longest ultraconserved sites genome wide, located near
      the essential neuronal transcription factor Arx, we used genome editing to create
      an expanded series of knockout mice lacking individual or combinations of
      ultraconserved enhancers. Mice with single or pairwise deletions of
      ultraconserved enhancers were viable and fertile but in nearly all cases showed
      neurological or growth abnormalities, including substantial alterations of neuron
      populations and structural brain defects. Our results demonstrate the functional
      importance of ultraconserved enhancers and indicate that remarkably strong
      sequence conservation likely results from fitness deficits that appear subtle in
      a laboratory setting.

PMID- 29358050
TI  - Multiscale Structuring of the E. coli Chromosome by Nucleoid-Associated and
      Condensin Proteins.
AB  - As in eukaryotes, bacterial genomes are not randomly folded. Bacterial genetic
      information is generally carried on a circular chromosome with a single origin of
      replication from which two replication forks proceed bidirectionally toward the
      opposite terminus region. Here, we investigate the higher-order architecture of
      the Escherichia coli genome, showing its partition into two structurally distinct
      entities by a complex and intertwined network of contacts: the replication
      terminus (ter) region and the rest of the chromosome. Outside of ter, the
      condensin MukBEF and the ubiquitous nucleoid-associated protein (NAP) HU promote
      DNA contacts in the megabase range. Within ter, the MatP protein prevents MukBEF
      activity, and contacts are restricted to ~280 kb, creating a domain with distinct
      structural properties. We also show how other NAPs contribute to nucleoid
      organization, such as H-NS, which restricts short-range interactions. Combined,
      these results reveal the contributions of major evolutionarily conserved proteins
      in a bacterial chromosome organization.

PMID- 29358051
TI  - Non-classical Immunity Controls Microbiota Impact on Skin Immunity and Tissue
      Repair.
AB  - Mammalian barrier surfaces are constitutively colonized by numerous
      microorganisms. We explored how the microbiota was sensed by the immune system
      and the defining properties of such responses. Here, we show that a skin
      commensal can induce T cell responses in a manner that is restricted to non
      classical MHC class I molecules. These responses are uncoupled from inflammation
      and highly distinct from pathogen-induced cells. Commensal-specific T cells
      express a defined gene signature that is characterized by expression of effector
      genes together with immunoregulatory and tissue-repair signatures. As such, non
      classical MHCI-restricted commensal-specific immune responses not only promoted
      protection to pathogens, but also accelerated skin wound closure. Thus, the
      microbiota can induce a highly physiological and pleiotropic form of adaptive
      immunity that couples antimicrobial function with tissue repair. Our work also
      reveals that non-classical MHC class I molecules, an evolutionarily ancient arm
      of the immune system, can promote homeostatic immunity to the microbiota.

PMID- 29358053
TI  - Parameters of metabolic quantification in clinical practice. Is it now time to
      include them in reports?
AB  - Qualitative techniques have traditionally been the standard for the diagnostic
      assessment with 18F-FDG PET studies. Since the introduction of the technique,
      quantitative parameters have been sought, more accurate and with better
      diagnostic precision, that may offer relevant information of the behavior,
      aggressiveness or prognosis of tumors. Nowadays, more and more studies with high
      quality evidence show the utility of other metabolic parameters different from
      the SUV maximum, which despite being widely used in clinical practice is
      controversial and many physicians still do not know its real meaning. The
      objective of this paper has been to review the key concepts of these metabolic
      parameters that could be relevant in normal practice in the future. It has been
      seen that there is more evidence in the complete evaluation of the metabolism of
      a lesion, through volumetric parameters that more adequately reflect the
      patient's tumor burden. Basically, these parameters calculate the volume of tumor
      that fulfills certain characteristics. A software available in the majority of
      the workstations has been used for this purpose and it has allowed to calculate
      these volumes using more or less complex criteria. The simplest threshold-based
      segmentation methods are available in most equipments, they are easy to calculate
      and they have been shown in many studies to have an important prognostic
      significance.

PMID- 29358052
TI  - Lipids Shape the Electron Acceptor-Binding Site of the Peripheral Membrane
      Protein Dihydroorotate Dehydrogenase.
AB  - The interactions between proteins and biological membranes are important for drug
      development, but remain notoriously refractory to structural investigation. We
      combine non-denaturing mass spectrometry (MS) with molecular dynamics (MD)
      simulations to unravel the connections among co-factor, lipid, and inhibitor
      binding in the peripheral membrane protein dihydroorotate dehydrogenase (DHODH),
      a key anticancer target. Interrogation of intact DHODH complexes by MS reveals
      that phospholipids bind via their charged head groups at a limited number of
      sites, while binding of the inhibitor brequinar involves simultaneous association
      with detergent molecules. MD simulations show that lipids support flexible
      segments in the membrane-binding domain and position the inhibitor and electron
      acceptor-binding site away from the membrane surface, similar to the electron
      acceptor-binding site in respiratory chain complex I. By complementing MS with MD
      simulations, we demonstrate how a peripheral membrane protein uses lipids to
      modulate its structure in a similar manner as integral membrane proteins.

PMID- 29358054
TI  - Assessment of poliovirus antibody seroprevalence in polio high risk areas of West
      Africa.
AB  - We conducted a serological survey of anti-polio antibodies in polio high-risk
      areas of Mali, Guinea and Cote d'Ivoire to assess risk of future poliovirus
      outbreaks. Random community sampling of children 6-11 and 36-48 months-old was
      conducted; neutralizing antibodies against poliovirus were detected using
      microneutralization assay. We analysed 1059/1064 (99.5%) of enrolled children.
      Seroprevalence to poliovirus type 1 (PV1) across all age groups and locations
      ranged between 92 and 100%, for PV2 it was 77-100%, and 89-95% for PV3. PV2
      seroprevalence in the younger age group in Guinea and Cote d'Ivoire was <80%.
      History of <4 polio vaccine doses and acute malnutrition were associated with
      seronegativity (OR = 2.1 CI95% = 1.5-3.1, OR = 1.8 CI95% = 1.1-3.3 respectively).
      The risk of poliovirus outbreak following importation is low because of high
      population immunity to PV1, however, due to large cohort of PV2 seronegative
      children any future detection of vaccine-derived poliovirus type 2 requires
      urgent response to arrest rapid spread.

PMID- 29358055
TI  - Systematic causality assessment of adverse events following HPV vaccines:
      Analysis of current data from Apulia region (Italy).
AB  - Since 2013, World Health Organization (WHO) recommended that adverse events
      following immunization (AEFIs) should be evaluated by a standardized algorithm
      for causality assessment, however the use of WHO procedure is rarely adopted. In
      Italy, AEFIs (classified only by temporal criteria) are registered in the
      National Drug Authority (AIFA) database, but causality assessment is not
      mandatory. Every year AIFA publishes the AEFIs report, that doesn't contain
      information about causal correlation between events and vaccines. From AIFA
      database, we selected AEFIs following human papillomavirus vaccination (HPV)
      reported in Apulia (about 4,000,000 inhabitants) during 2008-2016. For serious
      AEFIs, we applied WHO causality assessment criteria; for cases hospitalized, we
      repeated the assessment getting additional information from health documentation.
      In 2008-2016, 100 HPV AEFIs (reporting rate: 17.8 per 100,000 doses) were
      registered of which 19 were serious (rate: 3.4 per 100,000 doses) and 12 led to
      hospitalization. After causality assessment, for 9 AEFIs the classification was
      "consistent causal association to immunization", for 3 indeterminate, for 5
      "inconsistent causal association to immunization" and for 2 not-classifiable.
      Among hospitalized patients, 5 AEFIs were consistent, 5 inconsistent, 1 not
      classifiable and 1 indeterminate; adding information from health documentation,
      the results were similar except for indeterminate and not classifiable AEFIs that
      turned into "not consistent". Only half of severe AEFIs could be associated with
      vaccination and this suggests that AIFA report provides a incomplete picture of
      HPV vaccine safety, with a risk for readers to confound "post hoc" and "propter
      hoc" approach without considering the causality assessment results. In the view
      of the systematic use of WHO causality assessment algorithm in the AEFI
      surveillance, the efforts of Public Health must be focused on the improvement of
      the quality of the information provided to reduce conclusions inter-observer
      variability; the routine follow-up of reports, also to collect additional
      information, must be guaranteed.

PMID- 29358056
TI  - Use of ENABL(r) adjuvant to increase the potency of an adenovirus-vectored foot
      and-mouth disease virus serotype A subunit vaccine.
AB  - A foot-and-mouth disease (FMD) recombinant subunit vaccine formulated with a
      lipid/polymer adjuvant was evaluated in two vaccine efficacy challenge studies in
      steers. The vaccine active ingredient is a replication-deficient human adenovirus
      serotype 5 vector encoding the FMD virus (FMDV) A24/Cruzeiro/BRA/55 capsid
      (AdtA24). In the first study, AdtA24 formulated in ENABL(r) adjuvant was compared
      to a fourfold higher dose of AdtA24 without adjuvant. Steers vaccinated with
      AdtA24 + ENABL(r) adjuvant developed a significantly higher virus neutralizing
      test (VNT) antibody titer and an improved clinical response following FMDV
      A24/Cruzeiro/BRA/55 intradermal lingual challenge at 14 days post-vaccination
      (dpv) than steers vaccinated with the active ingredient alone. In the second
      study, vaccination with AdtA24 formulated in ENABL(r) at the same dose used in
      the first study, followed by FMDV A24/Cruzeiro/BRA/55 challenge on 7 or 14 dpv,
      prevented clinical FMD in all steers and conferred 90% protection against
      viremia. In addition, post-challenge FMDV titers in nasal samples from vaccinated
      steers compared to unvaccinated steers were significantly reduced. In both
      studies, none of the AdtA24 vaccinated steers developed antibodies to the FMDV
      non-structural proteins prior to challenge with FMDV, indicative of the capacity
      to differentiate infected from vaccinated animals (DIVA). These results
      demonstrate that administration of AdtA24 formulated in ENABL(r) adjuvant lowered
      the protective dose and prevented clinical FMD following exposure of vaccinated
      steers to virulent FMDV at 7 or 14 dpv.

PMID- 29358057
TI  - A bivalent vaccine derived from attenuated Salmonella expressing O-antigen
      polysaccharide provides protection against avian pathogenic Escherichia coli O1
      and O2 infection.
AB  - Avian pathogenic Escherichia coli (APEC), a leading cause of avian airsacculitis
      and colibacillosis, is responsible for significant economic loss in the poultry
      industry. APEC serogroups O1, O2, and O78 are predominantly associated with
      disease. Lipopolysaccharide (LPS) O-antigen has been shown to be a potent antigen
      for inducing specific protective immune responses. Therefore, we sought to
      develop a multivalent polysaccharide vaccine to prevent most APEC infections. We
      previously reported the stable expression of plasmid pSS27 encoding the APEC O1 O
      antigen gene cluster (10.8 kb) in attenuated Salmonella enterica serovar
      Typhimurium S740 provided excellent protection against APEC O1 challenge. In this
      study, the plasmid pSS28 harboring the APEC O2 O-antigen polysaccharide gene
      cluster (15.5 kb) was constructed. Biosynthesis of pSS28-encoded APEC O2 O
      antigen in Salmonella vaccine strain S740 was validated by Western blot. The
      recombinant Salmonella vaccine strain S740 (pSS28) elicited homologous protection
      against virulent wild-type APEC O2 challenge in a chicken model. Furthermore,
      through equal-volume mixing the two monovalent vaccine strains S740 (pSS27) and
      S740 (pSS28), a bivalent vaccine candidate against both APEC O1 and O2 was
      developed. Immunization of chickens with the bivalent vaccine elicited production
      of serum IgG and mucosal sIgA antibodies against the LPS of both APEC O1 and O2.
      Moreover, antibodies induced by the bivalent vaccine promoted opsonization,
      provoked complement-mediated bactericidal activity, and elicited protection
      against lethal challenge with both virulent APEC O1 and O2 strains. These results
      demonstrate that the bivalent vaccine comprised of S740 (pSS27) and S740 (pSS28)
      is a promising vaccine candidate against APEC O1 and O2 infection.

PMID- 29358058
TI  - Reply to Christian D. Fankhauser, Nico C. Grossmann, Joerg Beyer, and Thomas
      Hermanns' Letter to the Editor re: Sophia C. Kamran, Thomas Seisen, Sarah C.
      Markt, et al. Contemporary Treatment Patterns and Outcomes for Clinical Stage IS
      Testicular Cancer. Eur Urol 2018;73:262-70.

PMID- 29358059
TI  - Efficacy, Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate
      specific Membrane Antigen-ligand Positron-emission Tomography/Computed Tomography
      in Early Biochemical Recurrent Prostate Cancer After Radical Prostatectomy.
AB  - : Recently, 68Ga-labeled prostate-specific membrane antigen (PSMA)-ligand
      positron-emission tomography (PET) imaging has been shown to improve detection
      rates in recurrent prostate cancer (PC). However, published studies include only
      small patient numbers at low prostate-specific antigen (PSA) values. For this
      study, 272 consecutive patients with biochemical recurrence after radical
      prostatectomy and PSA value between 0.2 and 1ng/ml were included. The 68Ga-PSMA
      ligand PET/computed tomography (CT) was evaluated, and detection rates were
      determined and correlated to various clinical variables using univariate and
      multivariable analyses. Subgroups of patients with very low (0.2-0.5ng/ml) and
      low (>0.5-1.0ng/ml) PSA values were analyzed. In total, lesions indicative of PC
      recurrence were detected in 55% (74/134) and 74% (102/138) with very low and low
      PSA values, respectively. Main sites of recurrence were pelvic or retroperitoneal
      lymph nodes metastases, followed by local recurrence and bone metastases with
      higher probability in the low versus very low PSA subgroup. Detection rates
      significantly increased with higher PSA values, primary pT>=3a, primary pN+
      disease, grade group >=4, previous radiation therapy, and concurrent androgen
      deprivation therapy (ADT) in univariate analysis. In a multivariable logistic
      regression model, concurrent ADT and PSA values were identified as most relevant
      predictors of positive 68Ga-PSMA-ligand PET/CT. Further, prediction nomograms
      were established, which may help in estimating pretest PSMA-ligand PET positivity
      in clinical practice. PATIENT SUMMARY: In our study, 68Ga-labeled prostate
      specific membrane antigen (PSMA)-ligand positron-emission tomography
      (PET)/computed tomography (CT) detected recurrent disease after radical
      prostatectomy in 55% (74/134) and 74% (102/138) of patients with very low (0.2
      0.5ng/ml) and low (>0.5-1.0ng/ml) prostate-specific antigen values, respectively.
      On the basis of these data, it seems reasonable to perform 68Ga-PSMA-ligand
      PET/CT also in patients with early biochemical recurrence, as it can tailor
      further therapy decisions (eg, local vs systemic treatment). The established
      prediction nomograms can further assist urologists in discussions on the use of
      68Ga-PSMA-ligand PET/CT with their patients in specific clinical settings.

PMID- 29358060
TI  - Journal Shopping and Pruning the Literature.

PMID- 29358061
TI  - Pott's Disease Resulting in Complete Cervical Vertebral Destruction.
AB  - Skeletal tuberculosis, otherwise known as Pott's disease, has been recognized for
      centuries. Although typically diagnosed in citizens from countries with endemic
      tuberculosis, long-term workers in these regions, such as military deployees, can
      also acquire the disease. We present a case report of a military veteran
      presenting with neck pain and initially diagnosed with cervical disc disease. The
      patient's pain progressed to the point of developing paresthesias in his
      bilateral upper extremities. Eventually, cervical spine radiographs were obtained
      that revealed complete cervical vertebral body destruction from spinal
      tuberculosis. Epidemiology, diagnosis, and treatment of the disorder are
      discussed.

PMID- 29358063
TI  - Priming of microbial microcystin degradation in biomass-fed gravity driven
      membrane filtration biofilms.
AB  - Gravity-driven membrane (GDM) filtration is a promising tool for low-cost
      decentralized drinking water production. The biofilms in GDM systems are able of
      removing harmful chemical components, particularly toxic cyanobacterial
      metabolites such as microcystins (MCs). This is relevant for the application of
      GDM filtration because anthropogenic nutrient input and climate change have led
      to an increase of toxic cyanobacterial blooms. However, removal of MCs in newly
      developing GDM biofilms is only established after a prolonged period of time.
      Since cyanobacterial blooms are transient phenomena, it is important to
      understand MC removal in mature biofilms with or without prior toxin exposure. In
      this study, the microbial community composition of GDM biofilms was investigated
      in systems fed with water from a lake with periodic blooms of MC-producing
      cyanobacteria. Two out of three experimental treatments were supplemented with
      dead biomass of a MC-containing cyanobacterial strain, or of a non-toxic mutant,
      respectively. Analysis of bacterial rRNA genes revealed that both biomass-amended
      treatments were significantly more similar to each other than to a non
      supplemented control. Therefore, it was hypothesized that biofilms could
      potentially be 'primed' for rapid MC removal by prior addition of non-toxic
      biomass. A subsequent experiment showed that MC removal developed significantly
      faster in mature biofilms that were pre-fed with biomass from the mutant strain
      than in unamended controls, indicating that MC degradation was a facultative
      trait of bacterial populations in GDM biofilms. The significant enrichment of
      bacteria related to both aerobic and anaerobic MC degraders suggested that this
      process might have occurred in parallel in different microniches.

PMID- 29358064
TI  - Evaluation of the Effect of Operator Experience on Outcome of Hepatic Artery
      Embolization of Hepatocellular Carcinoma in a Tertiary Cancer Center.
AB  - RATIONALE AND OBJECTIVES: There is lack of information on the learning curve and
      the effect of operator's experience on the quality outcomes of transarterial
      hepatic embolization (TAE). The aim of this study was to evaluate the effect of
      operator experience on outcomes of TAE of hepatocellular carcinoma. MATERIALS AND
      METHODS: Demographic characteristics and outcomes including overall survival
      (OS), time to local tumor progression (TLP), and post-procedure complications in
      patients with hepatocellular carcinoma treated with TAE were collected.
      Operators' experience was measured in years based on the years after completion
      of fellowship and the date of first embolization, and was divided into five
      groups: G1, less than 5 years of operator's experience (YOE) at the time of first
      embolization; G2, 5-10 YOE; G3, 10-15 YOE; G4, 15-20 YOE; and G5, more than 20
      YOE. The effects of operator's experience and outcomes were assessed using linear
      regression. RESULTS: From January 2012 to January 2015, 93 patients (age range =
      30-86 years) were treated. The number of patients treated by each group was as
      follows: G1 = 12; G2 = 8; G3 = 23; G4 = 5; and G5 = 45. All groups were similar
      in regard to degree of cirrhosis, Barcelona Clinic Liver Cancer staging, and
      Child-Pugh score (P > .05). Median TLP was 8.8 months. TLP was 7.0, 6.8, 19.2,
      7.9, and 8.2 months in G1, G2, G3, G4, and G5, respectively (P = .56). OS for 1,
      2, and 3 years was 75%, 56%, and 42% for G1; 87%, 54%, and 54% for G2; 91%, 71%,
      and 45% for G3, 100%, 50%, and 0 for G4; and 84%, 65%, and 40% for G5.
      CONCLUSION: Among interventional radiology fellowship-trained operators in a
      tertiary cancer center, OS, TLP, and post-procedure complications of TAE were not
      affected by the years of post-fellowship experience.

PMID- 29358065
TI  - Knowledge and beliefs about chronic non cancer pain management for family
      medicine group nurses.

PMID- 29358066
TI  - Portomesenteric vein thrombosis in sleeve gastrectomy: a 10-year review.
AB  - BACKGROUND: Worldwide, the laparoscopic sleeve gastrectomy (LSG) is becoming the
      dominant bariatric procedure due to its reliable weight loss and low complication
      rate. Portomesenteric vein thrombosis (PVT) is an uncommon complication of LSG
      with an incidence of .3% to 1% and can lead to serious consequences, such as
      bowel ischemia and death. OBJECTIVES: This paper will present the presentation,
      risk factors, treatment, and long-term outcomes of patients who had PVT post-LSG.
      SETTING: Five bariatric centers in a private setting in Australia. METHODS:
      Retrospective data were collected from 5 bariatric centers across Australia from
      2007 to 2016. RESULTS: Across 5 centers, 5951 patients underwent LSG; 18 had
      recognized PVT (.3%). The mean body mass index was 41.8. Of patients, 39% had a
      history or family history of deep vein thrombosis. The average time to diagnosis
      was 13 days (range, 5-25). Treatment was nonoperative with anticoagulation in
      94%. One patient required operative management with bowel resection. All patients
      were discharged on therapeutic anticoagulation. Mean total weight loss was 27.7%
      (14.8%-66.3%). Mean follow-up was 10 months. There were no mortalities. Given the
      low number of patients, no statistically significant data could be derived.
      CONCLUSION: PVT is difficult to diagnose, with significant consequences. The
      presenting symptoms are nonspecific, and a high index of suspicion needs to be
      maintained. Cross-sectional imaging with computed tomography of the abdomen is
      recommended. Patients with PVT post-LSG without previous risk factors can be
      anticoagulated for 3 to 6 months with an international normalized ratio of 2 to
      3.

PMID- 29358067
TI  - Midterm outcomes of laparoscopic sleeve gastrectomy as a stand-alone procedure in
      super-obese patients.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has been gaining popularity as
      a safe and effective bariatric procedure for patients with morbid obesity.
      However, the long-term outcomes of LSG alone in patients with body mass index
      over 50 kg/m2, or super obesity, have not been analyzed in comparison to those of
      other bariatric procedures. OBJECTIVES: This study aimed to compare midterm
      results of LSG and laparoscopic Roux-en-Y gastric bypass (RYGB) and to evaluate
      the efficacy of LSG as a stand-alone bariatric procedure for patients with super
      obesity. SETTING: Tertiary medical center. METHODS: The 3-year outcomes of 607
      super-obese patients who underwent either LSG or RYGB at an academic institution
      between December 2003 and February 2012 were retrospectively reviewed. Patient
      records at 6, 12, 18, 24, and 36 months of follow-up were analyzed. RESULTS: The
      average percent excess weight loss and change in body mass index of the LSG
      versus RYGB group showed no significant difference at any follow-up period. The
      rate of resolution of type 2 diabetes and the mean hemoglobin A1C level in both
      groups were also comparable. The dramatic loss of patient data beginning at the
      12-month follow-up (220/607, 36.24%) was also analyzed. The surgery type was
      associated with the duration of follow-up at .133, with a P value of .001.
      CONCLUSIONS: We concluded that LSG is a comparably effective stand-alone
      procedure for patients with super obesity as RYGB. Our study is the first to
      suggest that compared with RYGB, LSG is associated with a shorter duration of
      postoperative follow-up.

PMID- 29358068
TI  - Single-Parent Expression Is a General Mechanism Driving Extensive Complementation
      of Non-syntenic Genes in Maize Hybrids.
AB  - Maize (Zea mays L.) displays an exceptional degree of structural genomic
      diversity [1, 2]. In addition, variation in gene expression further contributes
      to the extraordinary phenotypic diversity and plasticity of maize. This study
      provides a systematic investigation on how distantly related homozygous maize
      inbred lines affect the transcriptomic plasticity of their highly heterozygous F1
      hybrids. The classical dominance model of heterosis explains the superiority of
      hybrid plants by the complementation of deleterious parental alleles by superior
      alleles of the second parent at many loci [3]. Genes active in one inbred line
      but inactive in another represent an extreme instance of allelic diversity
      defined as single-parent expression [4]. We observed on average ~1,000 such genes
      in all inbred line combinations during primary root development. These genes
      consistently displayed expression complementation (i.e., activity) in their
      hybrid progeny. Consequently, extreme expression complementation is a general
      mechanism that results on average in ~600 additionally active genes and their
      encoded biological functions in hybrids. The modern maize genome is complemented
      by a set of non-syntenic genes, which emerged after the separation of the maize
      and sorghum lineages and lack syntenic orthologs in any other grass species [5].
      We demonstrated that non-syntenic genes are the driving force of gene expression
      complementation in hybrids. Among those, the highly diversified families of bZIP
      and bHLH transcription factors [6] are systematically overrepresented. In
      summary, extreme gene expression complementation extensively shapes the
      transcriptomic plasticity of maize hybrids and might therefore be one factor
      controlling the developmental plasticity of hybrids.

PMID- 29358069
TI  - Pupil Size Coupling to Cortical States Protects the Stability of Deep Sleep via
      Parasympathetic Modulation.
AB  - During wakefulness, pupil diameter can reflect changes in attention, vigilance,
      and cortical states. How pupil size relates to cortical activity during sleep,
      however, remains unknown. Pupillometry during natural sleep is inherently
      challenging since the eyelids are usually closed. Here, we present a novel head
      fixed sleep paradigm in combination with infrared back-illumination pupillometry
      (iBip) allowing robust tracking of pupil diameter in sleeping mice. We found that
      pupil size can be used as a reliable indicator of sleep states and that cortical
      activity becomes tightly coupled to pupil size fluctuations during non-rapid eye
      movement (NREM) sleep. Pharmacological blocking experiments indicate that the
      observed pupil size changes during sleep are mediated via the parasympathetic
      system. We furthermore found that constrictions of the pupil during NREM episodes
      might play a protective role for stability of sleep depth. These findings reveal
      a fundamental relationship between cortical activity and pupil size, which has so
      far been hidden behind closed eyelids.

PMID- 29358070
TI  - Hunter-Gatherer Olfaction Is Special.
AB  - People struggle to name odors [1-4]. This has been attributed to a diminution of
      olfaction in trade-off to vision [5-10]. This presumption has been challenged
      recently by data from the hunter-gatherer Jahai who, unlike English speakers,
      find odors as easy to name as colors [4]. Is the superior olfactory performance
      among the Jahai because of their ecology (tropical rainforest), their language
      family (Aslian), or because of their subsistence (they are hunter-gatherers)? We
      provide novel evidence from the hunter-gatherer Semaq Beri and the non-hunter
      gatherer (swidden-horticulturalist) Semelai that subsistence is the critical
      factor. Semaq Beri and Semelai speakers-who speak closely related languages and
      live in the tropical rainforest of the Malay Peninsula-took part in a controlled
      odor- and color-naming experiment. The swidden-horticulturalist Semelai found
      odors much more difficult to name than colors, replicating the typical Western
      finding. But for the hunter-gatherer Semaq Beri odor naming was as easy as color
      naming, suggesting that hunter-gatherer olfactory cognition is special.

PMID- 29358071
TI  - Prefrontal Control of Visual Distraction.
AB  - Avoiding distraction by conspicuous but irrelevant stimuli is critical to
      accomplishing daily tasks. Regions of prefrontal cortex control attention by
      enhancing the representation of task-relevant information in sensory cortex,
      which can be measured in modulation of both single neurons and event-related
      electrical potentials (ERPs) on the cranial surface [1, 2]. When irrelevant
      information is particularly conspicuous, it can distract attention and interfere
      with the selection of behaviorally relevant information. Such distraction can be
      minimized via top-down control [3-5], but the cognitive and neural mechanisms
      giving rise to this control over distraction remain uncertain and debated [6-9].
      Bridging neurophysiology to electrophysiology, we simultaneously recorded neurons
      in prefrontal cortex and ERPs over extrastriate visual cortex to track the
      processing of salient distractors during a visual search task. Critically, when
      the salient distractor was successfully ignored, but not otherwise, we observed
      robust suppression of salient distractor representations. Like target selection,
      the distractor suppression was observed in prefrontal cortex before it appeared
      over extrastriate cortical areas. Furthermore, all prefrontal neurons that showed
      suppression of the task-irrelevant distractor also contributed to selecting the
      target. This suggests a common prefrontal mechanism is responsible for both
      selecting task-relevant and suppressing task-irrelevant information in sensory
      cortex. Taken together, our results resolve a long-standing debate over the
      mechanisms that prevent distraction, and provide the first evidence directly
      linking suppressed neural firing in prefrontal cortex with surface ERP measures
      of distractor suppression.

PMID- 29358072
TI  - A Transient Rise in Free Mg2+ Ions Released from ATP-Mg Hydrolysis Contributes to
      Mitotic Chromosome Condensation.
AB  - For cell division, negatively charged chromatin, in which nucleosome fibers (10
      nm fibers) are irregularly folded [1-5], must be condensed into chromosomes and
      segregated. While condensin and other proteins are critical for organizing
      chromatin into the appropriate chromosome shape [6-17], free divalent cations
      such as Mg2+ and Ca2+, which condense chromatin or chromosomes in vitro [18-28],
      have long been considered important, especially for local condensation, because
      the nucleosome fiber has a net negative charge and is by itself stretched like
      "beads on a string" by electrostatic repulsion. For further folding, other
      positively charged factors are required to decrease the charge and repulsion
      [29]. However, technical limitations to measure intracellular free divalent
      cations, but not total cations [30], especially Mg2+, have prevented us from
      elucidating their function. Here, we developed a Forster resonance energy
      transfer (FRET)-based Mg2+ indicator that monitors free Mg2+ dynamics throughout
      the cell cycle. By combining this indicator with Ca2+ [31] and adenosine
      triphosphate (ATP) [32] indicators, we demonstrate that the levels of free Mg2+,
      but not Ca2+, increase during mitosis. The Mg2+ increase is coupled with a
      decrease in ATP, which is normally bound to Mg2+ in the cell [33]. ATP inhibited
      Mg2+-dependent chromatin condensation in vitro. Chelating Mg2+ induced mitotic
      cell arrest and chromosome decondensation, while ATP reduction had the opposite
      effect. Our results suggest that ATP-bound Mg2+ is released by ATP hydrolysis and
      contributes to mitotic chromosome condensation with increased rigidity,
      suggesting a novel regulatory mechanism for higher-order chromatin organization
      by the intracellular Mg2+-ATP balance.

PMID- 29358073
TI  - Phase Entrainment of Brain Oscillations Causally Modulates Neural Responses to
      Intelligible Speech.
AB  - Due to their periodic nature, neural oscillations might represent an optimal
      "tool" for the processing of rhythmic stimulus input [1-3]. Indeed, the alignment
      of neural oscillations to a rhythmic stimulus, often termed phase entrainment,
      has been repeatedly demonstrated [4-7]. Phase entrainment is central to current
      theories of speech processing [8-10] and has been associated with successful
      speech comprehension [11-17]. However, typical manipulations that reduce speech
      intelligibility (e.g., addition of noise and time reversal [11, 12, 14, 16, 17])
      could destroy critical acoustic cues for entrainment (such as "acoustic edges"
      [7]). Hence, the association between phase entrainment and speech intelligibility
      might only be "epiphenomenal"; i.e., both decline due to the same manipulation,
      without any causal link between the two [18]. Here, we use transcranial
      alternating current stimulation (tACS [19]) to manipulate the phase lag between
      neural oscillations and speech rhythm while measuring neural responses to
      intelligible and unintelligible vocoded stimuli with sparse fMRI. We found that
      this manipulation significantly modulates the BOLD response to intelligible
      speech in the superior temporal gyrus, and the strength of BOLD modulation is
      correlated with a phasic modulation of performance in a behavioral task.
      Importantly, these findings are absent for unintelligible speech and during sham
      stimulation; we thus demonstrate that phase entrainment has a specific, causal
      influence on neural responses to intelligible speech. Our results not only
      provide an important step toward understanding the neural foundation of human
      abilities at speech comprehension but also suggest new methods for enhancing
      speech perception that can be explored in the future.

PMID- 29358074
TI  - [Post micturition incontinence and Cowper's syringocele: 3 new case reports].

PMID- 29358075
TI  - Initial development and pilot testing of observer-reported outcomes (ObsROs) for
      children with cystic fibrosis ages 0-11years.
AB  - PURPOSE: Patient-reported outcomes are important clinical trial endpoints. Young
      children may not be able to reliably report on how they feel or function, so
      observer-reported outcomes (ObsROs) may be more appropriate for them. The purpose
      of this study was to develop and pilot field test electronic parent-reported
      observational instruments for children with cystic fibrosis (CF) 0-6 and 7
      11years of age. METHODS: We performed concept elicitation interviews with parents
      of children with CF <=11years of age to elicit the respiratory signs they could
      observe at baseline and during an acute respiratory illness. The resulting
      instruments were refined based on interviews with parents and clinicians. We
      conducted a pilot field test to evaluate test-retest reliability and the ability
      of items to distinguish well and sick periods. RESULTS: The instruments consist
      of 17 items assessing respiratory signs and observable CF-related impacts. Test
      retest reliability was acceptable for both age groups but discrimination was low
      for ages 7-11, likely reflecting less direct observation of older children by
      their parents. CONCLUSIONS: An ObsRO for children with CF ages 0-6 appears
      promising, while self-report may be more appropriate for children >6years of age.
      Next steps for the 0-6year old instrument will be utilizing it as an exploratory
      endpoint in clinical trials to enable item reduction, scale development, and
      further reliability and validity testing. Ultimately, this ObsRO could be a
      promising endpoint for early intervention trials in young children with CF.

PMID- 29358076
TI  - Mechanistic View of hnRNPA2 Low-Complexity Domain Structure, Interactions, and
      Phase Separation Altered by Mutation and Arginine Methylation.
AB  - hnRNPA2, a component of RNA-processing membraneless organelles, forms inclusions
      when mutated in a syndrome characterized by the degeneration of neurons (bearing
      features of amyotrophic lateral sclerosis [ALS] and frontotemporal dementia),
      muscle, and bone. Here we provide a unified structural view of hnRNPA2 self
      assembly, aggregation, and interaction and the distinct effects of small chemical
      changes-disease mutations and arginine methylation-on these assemblies. The
      hnRNPA2 low-complexity (LC) domain is compact and intrinsically disordered as a
      monomer, retaining predominant disorder in a liquid-liquid phase-separated form.
      Disease mutations D290V and P298L induce aggregation by enhancing and extending,
      respectively, the aggregation-prone region. Co-aggregating in disease inclusions,
      hnRNPA2 LC directly interacts with and induces phase separation of TDP-43.
      Conversely, arginine methylation reduces hnRNPA2 phase separation, disrupting
      arginine-mediated contacts. These results highlight the mechanistic role of
      specific LC domain interactions and modifications conserved across many hnRNP
      family members but altered by aggregation-causing pathological mutations.

PMID- 29358077
TI  - Evidence against Stable Protein S-Nitrosylation as a Widespread Mechanism of Post
      translational Regulation.
AB  - S-nitrosation, commonly referred to as S-nitrosylation, is widely regarded as a
      ubiquitous, stable post-translational modification that directly regulates many
      proteins. Such a widespread role would appear to be incompatible with the
      inherent lability of the S-nitroso bond, especially its propensity to rapidly
      react with thiols to generate disulfide bonds. As anticipated, we observed robust
      and widespread protein S-nitrosation after exposing cells to nitrosocysteine or
      lipopolysaccharide. Proteins detected using the ascorbate-dependent biotin switch
      method are typically interpreted to be directly regulated by S-nitrosation.
      However, these S-nitrosated proteins are shown to predominantly comprise
      transient intermediates leading to disulfide bond formation. These disulfides are
      likely to be the dominant end effectors resulting from elevations in nitrosating
      cellular nitric oxide species. We propose that S-nitrosation primarily serves as
      a transient intermediate leading to disulfide formation. Overall, we conclude
      that the current widely held perception that stable S-nitrosation directly
      regulates the function of many proteins is significantly incorrect.

PMID- 29358079
TI  - Bacterial RNA Biology on a Genome Scale.
AB  - Bacteria are an exceedingly diverse group of organisms whose molecular
      exploration is experiencing a renaissance. While the classical view of bacterial
      gene expression was relatively simple, the emerging view is more complex,
      encompassing extensive post-transcriptional control involving riboswitches, RNA
      thermometers, and regulatory small RNAs (sRNAs) associated with the RNA-binding
      proteins CsrA, Hfq, and ProQ, as well as CRISPR/Cas systems that are programmed
      by RNAs. Moreover, increasing interest in members of the human microbiota and
      environmental microbial communities has highlighted the importance of
      understudied bacterial species with largely unknown transcriptome structures and
      RNA-based control mechanisms. Collectively, this creates a need for global RNA
      biology approaches that can rapidly and comprehensively analyze the RNA
      composition of a bacterium of interest. We review such approaches with a focus on
      RNA-seq as a versatile tool to investigate the different layers of gene
      expression in which RNA is made, processed, regulated, modified, translated, and
      turned over.

PMID- 29358078
TI  - A Multiplex Enzymatic Machinery for Cellular Protein S-nitrosylation.
AB  - S-nitrosylation, the oxidative modification of Cys residues by nitric oxide (NO)
      to form S-nitrosothiols (SNOs), modifies all main classes of proteins and
      provides a fundamental redox-based cellular signaling mechanism. However, in
      contrast to other post-translational protein modifications, S-nitrosylation is
      generally considered to be non-enzymatic, involving multiple chemical routes. We
      report here that endogenous protein S-nitrosylation in the model organism E. coli
      depends principally upon the enzymatic activity of the hybrid cluster protein
      Hcp, employing NO produced by nitrate reductase. Anaerobiosis on nitrate induces
      both Hcp and nitrate reductase, thereby resulting in the S-nitrosylation
      dependent assembly of a large interactome including enzymes that generate NO (NO
      synthase), synthesize SNO-proteins (SNO synthase), and propagate SNO-based
      signaling (trans-nitrosylases) to regulate cell motility and metabolism. Thus,
      protein S-nitrosylation by NO in E. coli is essentially enzymatic, and the
      potential generality of the multiplex enzymatic mechanism that we describe may
      support a re-conceptualization of NO-based cellular signaling.

PMID- 29358080
TI  - A Regulatory Module Controlling Homeostasis of a Plant Immune Kinase.
AB  - Plant pattern recognition receptors (PRRs) perceive microbial and endogenous
      molecular patterns to activate immune signaling. The cytoplasmic kinase BIK1 acts
      downstream of multiple PRRs as a rate-limiting component, whose phosphorylation
      and accumulation are central to immune signal propagation. Previous work
      identified the calcium-dependent protein kinase CPK28 and heterotrimeric G
      proteins as negative and positive regulators of BIK1 accumulation, respectively.
      However, mechanisms underlying this regulation remain unknown. Here we show that
      the plant U-box proteins PUB25 and PUB26 are homologous E3 ligases that mark BIK1
      for degradation to negatively regulate immunity. We demonstrate that the
      heterotrimeric G proteins inhibit PUB25/26 activity to stabilize BIK1, whereas
      CPK28 specifically phosphorylates conserved residues in PUB25/26 to enhance their
      activity and promote BIK1 degradation. Interestingly, PUB25/26 specifically
      target non-activated BIK1, suggesting that activated BIK1 is maintained for
      immune signaling. Our findings reveal a multi-protein regulatory module that
      enables robust yet tightly regulated immune responses.

PMID- 29358081
TI  - The Circle of Gratitude.

PMID- 29358082
TI  - Learning lessons: The need for effective evaluation of regulatory change.

PMID- 29358084
TI  - Intestinal Epithelial Cell Autophagy Is Required to Protect against TNF-Induced
      Apoptosis during Chronic Colitis in Mice.
AB  - Genome-wide association studies have linked polymorphisms in the autophagy gene
      ATG16L1 with susceptibility to inflammatory bowel disease (IBD). However, the
      cell-type-specific effects of autophagy on the regulation of chronic intestinal
      inflammation have not been investigated. Here, we assessed the effect of myeloid
      specific or intestinal epithelial cell (IEC)-specific deletion of Atg16l1 on
      chronic colitis triggered by the intestinal opportunistic pathogen Helicobacter
      hepaticus in mice. Although Atg16l1 deficiency in myeloid cells had little effect
      on disease, mice selectively lacking Atg16l1 in IECs (Atg16l1VC) developed
      severely exacerbated pathology, accompanied by elevated pro-inflammatory cytokine
      secretion and increased IEC apoptosis. Using ex vivo IEC organoids, we
      demonstrate that autophagy intrinsically controls TNF-induced apoptosis and in
      vivo blockade of TNF attenuated the exacerbated pathology in Atg16l1VC mice.
      These findings suggest that the IBD susceptibility gene ATG16L1 and the process
      of autophagy within the epithelium control inflammation-induced apoptosis and
      barrier integrity to limit chronic intestinal inflammation.

PMID- 29358083
TI  - Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii
      Mediated Inflammation.
AB  - The protozoan parasite Toxoplasma gondii triggers severe small intestinal
      immunopathology characterized by IFN-gamma- and intestinal microbiota-mediated
      inflammation, Paneth cell loss, and bacterial dysbiosis. Paneth cells are a
      prominent secretory epithelial cell type that resides at the base of intestinal
      crypts and releases antimicrobial peptides. We demonstrate that the microbiota
      triggers basal Paneth cell-specific autophagy via induction of IFN-gamma, a known
      trigger of autophagy, to maintain intestinal homeostasis. Deletion of the
      autophagy protein Atg5 specifically in Paneth cells results in exaggerated
      intestinal inflammation characterized by complete destruction of the intestinal
      crypts resembling that seen in pan-epithelial Atg5-deficient mice. Additionally,
      lack of functional autophagy in Paneth cells within intestinal organoids and T.
      gondii-infected mice causes increased sensitivity to the proinflammatory cytokine
      TNF along with increased intestinal permeability, leading to exaggerated
      microbiota- and IFN-gamma-dependent intestinal immunopathology. Thus, Atg5
      expression in Paneth cells is essential for tissue protection against cytokine
      mediated immunopathology during acute gastrointestinal infection.

PMID- 29358085
TI  - Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance.
AB  - The heterochromatin protein 1 (HP1) family is involved in various functions with
      maintenance of chromatin structure. During murine somatic cell reprogramming, we
      find that early depletion of HP1gamma reduces the generation of induced
      pluripotent stem cells, while late depletion enhances the process, with a
      concomitant change from a centromeric to nucleoplasmic localization and
      elongation-associated histone H3.3 enrichment. Depletion of heterochromatin
      anchoring protein SENP7 increased reprogramming efficiency to a similar extent as
      HP1gamma, indicating the importance of HP1gamma release from chromatin for
      pluripotency acquisition. HP1gamma interacted with OCT4 and DPPA4 in HP1alpha and
      HP1beta knockouts and in H3K9 methylation depleted H3K9M embryonic stem cell
      (ESC) lines. HP1alpha and HP1gamma complexes in ESCs differed in association with
      histones, the histone chaperone CAF1 complex, and specific components of
      chromatin-modifying complexes such as DPY30, implying distinct functional
      contributions. Taken together, our results reveal the complex contribution of the
      HP1 proteins to pluripotency.

PMID- 29358086
TI  - MEIS1 Regulates Hemogenic Endothelial Generation, Megakaryopoiesis, and
      Thrombopoiesis in Human Pluripotent Stem Cells by Targeting TAL1 and FLI1.
AB  - Human pluripotent stem cells (hPSCs) provide an unlimited source for generating
      various kinds of functional blood cells. However, efficient strategies for
      generating large-scale functional blood cells from hPSCs are still lacking, and
      the mechanism underlying human hematopoiesis remains largely unknown. In this
      study, we identified myeloid ectopic viral integration site 1 homolog (MEIS1) as
      a crucial regulator of hPSC early hematopoietic differentiation. MEIS1 is vital
      for specification of APLNR+ mesoderm progenitors to functional hemogenic
      endothelial progenitors (HEPs), thereby controlling formation of hematopoietic
      progenitor cells (HPCs). TAL1 mediates the function of MEIS1 in HEP
      specification. In addition, MEIS1 is vital for megakaryopoiesis and
      thrombopoiesis from hPSCs. Mechanistically, FLI1 acts as a downstream gene
      necessary for the function of MEIS1 during megakaryopoiesis. Thus, MEIS1 controls
      human hematopoiesis in a stage-specific manner and can be potentially manipulated
      for large-scale generation of HPCs or platelets from hPSCs for therapeutic
      applications in regenerative medicine.

PMID- 29358087
TI  - Triple S-Phase Labeling of Dividing Stem Cells.
AB  - Marking replicating DNA with multiple labels presents the possibility of
      revealing new features and mechanisms of DNA synthesis and cell division;
      however, progression beyond double labeling has been hampered by cross-reactivity
      of label detection and scarcity of appropriate labels. Here, we present a method
      for triple S-phase labeling of the dividing cells, with a fourth label used to
      mark cells actively engaged in cell-cycle progression (e.g., using Ki67) or to
      phenotype the dividing cells or their progeny (e.g., using a GFP-expressing
      lineage reporter transgene). We apply this method to determine the parameters of
      neural stem cell division in the adult brain, to birth date up to four cohorts of
      dividing cells, and to reveal patterns of stem cell division in non-neural
      tissues.

PMID- 29358088
TI  - Isogenic FUS-eGFP iPSC Reporter Lines Enable Quantification of FUS Stress Granule
      Pathology that Is Rescued by Drugs Inducing Autophagy.
AB  - Perturbations in stress granule (SG) dynamics may be at the core of amyotrophic
      lateral sclerosis (ALS). Since SGs are membraneless compartments, modeling their
      dynamics in human motor neurons has been challenging, thus hindering the
      identification of effective therapeutics. Here, we report the generation of
      isogenic induced pluripotent stem cells carrying wild-type and P525L FUS-eGFP. We
      demonstrate that FUS-eGFP is recruited into SGs and that P525L profoundly alters
      their dynamics. With a screening campaign, we demonstrate that PI3K/AKT/mTOR
      pathway inhibition increases autophagy and ameliorates SG phenotypes linked to
      P525L FUS by reducing FUS-eGFP recruitment into SGs. Using a Drosophila model of
      FUS-ALS, we corroborate that induction of autophagy significantly increases
      survival. Finally, by screening clinically approved drugs for their ability to
      ameliorate FUS SG phenotypes, we identify a number of brain-penetrant anti
      depressants and anti-psychotics that also induce autophagy. These drugs could be
      repurposed as potential ALS treatments.

PMID- 29358090
TI  - Integrating multisensory information across external and motor-based frames of
      reference.
AB  - In the mirror box illusion, participants often report that their hand is located
      where they see it, even when the position of the reflected hand differs from the
      actual position of their hand. This illusory shift (an index of multisensory
      integration) is stronger when the two hands engage in synchronous bimanual
      movement, in which visual and proprioceptive information is congruent in both
      motor-based (i.e. coordinate centered on the effector) and external (i.e.
      coordinates centered on elements external to the effector) frames of reference.
      To investigate the separate contributions of external and motor-based congruence
      in multisensory integration, we instructed participants to make synchronous or
      asynchronous tapping movements in either the same (i.e. both hands palms up) or
      opposing (palm up, palm down) postures. When in opposing postures, externally
      congruent movements were incongruent in a motor-based frame of reference, and
      vice versa. Across three experiments, participants reported more illusory shift
      and stronger ownership of the viewed hand in the mirror for external versus motor
      based congruence trials regardless of motor outflow or motor effort, indicating
      that information from an externally-based representation is more strongly
      weighted in multisensory integration. These findings provide evidence that not
      only information across sensory modalities, but also information regarding
      crossmodal congruence represented in different spatial frames of reference, is
      differentially weighted in multisensory integration. We discuss how our findings
      can be incorporated into current computational models on multisensory
      integration.

PMID- 29358089
TI  - BAK/BAX-Mediated Apoptosis Is a Myc-Induced Roadblock to Reprogramming.
AB  - Despite intensive efforts to optimize the process, reprogramming differentiated
      cells to induced pluripotent stem cells (iPSCs) remains inefficient. The most
      common combination of transcription factors employed comprises OCT4, KLF4, SOX2,
      and MYC (OKSM). If MYC is omitted (OKS), reprogramming efficiency is reduced
      further. Cells must overcome several obstacles to reach the pluripotent state,
      one of which is apoptosis. To directly determine how extensively apoptosis limits
      reprogramming, we exploited mouse embryonic fibroblasts (MEFs) lacking the two
      essential mediators of apoptosis, BAK and BAX. Our results show that
      reprogramming is enhanced in MEFs deficient in BAK and BAX, but only when MYC is
      part of the reprogramming cocktail. Thus, the propensity for Myc overexpression
      to elicit apoptosis creates a significant roadblock to reprogramming under OKSM
      conditions. Our results suggest that blocking apoptosis during reprogramming may
      enhance the derivation of iPSCs for research and therapeutic purposes.

PMID- 29358091
TI  - Voulez-vous jouer avec moi? Twelve-month-olds understand that foreign languages
      can communicate.
AB  - Infants understand that speech in their native language allows speakers to
      communicate. Is this understanding limited to their native language or does it
      extend to non-native languages with which infants have no experience? Twelve
      month-old infants saw an actor, the Communicator, repeatedly select one of two
      objects. When the Communicator could no longer reach the target but a Recipient
      could, the Communicator vocalized a nonsense phrase either in English (infants'
      native language), Spanish (rhythmically different), or Russian (phonotactically
      different), or hummed (a non-speech vocalization). Across all three languages,
      native and non-native, but not humming, infants looked longer when the Recipient
      gave the Communicator the non-target object. Although, by 12 months, infants do
      not readily map non-native words to objects or discriminate most non-native
      speech contrasts, they understand that non-native languages can transfer
      information to others. Understanding language as a tool for communication extends
      beyond infants' native language: By 12 months, infants view language as a
      universal mechanism for transferring and acquiring new information.

PMID- 29358092
TI  - Nitroolefin-based BODIPY as a novel water-soluble ratiometric fluorescent probe
      for detection of endogenous thiols.
AB  - Small molecule biothiols, including cysteine (Cys), homocysteine (Hcy), and
      glutathione (GSH), play many crucial roles in physiological processes. In this
      work, we have prepared a nitroolefin-based BODIPY fluorescent probe with
      excellent water solubility for detection thiols, which displayed ratiometric
      fluorescent signal for thiols. Incorporation of a nitroolefin unit to the BODIPY
      dye would transform it into a strong Michael acceptor, which would be highly
      susceptible to sulfhydryl nucleophiles. This probe shows an obvious ratio change
      upon response with thiols, an increase of the emission at 517 nm along with a
      concomitant decrease of fluorescence peak at 573 nm. Moreover, these successes of
      intracellular imaging experiments in A549 cells indicated that this probe is
      suitable for imaging of ex-/endogenous thiols in living cells.

PMID- 29358093
TI  - Spectroscopic and theoretical investigation of conformational changes of proteins
      by synthesized pyrimidine derivative and its sensitivity towards FRET
      application.
AB  - Interest in synthesizing and characterizing (IR, NMR and HRMS spectroscopic
      methods) a pyrimidine based Schiff-base ligand, 2-(2-(Anthracen-9-ylmethylene)
      hydrazinyl)-4,6-dimethyl pyrimidine (ANHP) has been developed for its application
      to ascertain the conformational change of protein and sensitivity towards
      fluorescence resonance energy transfer (FRET) process. Location of ANHP in bovine
      serum albumin (BSA) and human serum albumin (HSA) proteins environment has been
      determined using different spectroscopic techniques. Weakly fluorescent ANHP have
      shown greater protein induced fluorescence enhancement (PIFE) in case of HSA than
      BSA, though in both cases energy transfer efficiency are almost same but
      difference in binding constant values encourages us to find the location of ANHP
      within the complex protein environment. From the FRET parameter and alpha
      helicity change, it has been found that ANHP bound with Trp-214 of HSA and
      surface Trp-134 of BSA. Conformational changes of proteins have been observed
      more for HSA than BSA in presence of ANHP, which has confirmed the location of
      ANHP in both the protein environments. Coupled with experimental studies,
      molecular docking analysis has also been done to explain the locations and
      distance dependent FRET process of ANHP in both proteins.

PMID- 29358094
TI  - How people learn about causal influence when there are many possible causes: A
      model based on informative transitions.
AB  - Four experiments tested how people learn cause-effect relations when there are
      many possible causes of an effect. When there are many cues, even if all the cues
      together strongly predict the effect, the bivariate relation between each
      individual cue and the effect can be weak, which can make it difficult to detect
      the influence of each cue. We hypothesized that when detecting the influence of a
      cue, in addition to learning from the states of the cues and effect (e.g., a cue
      is present and the effect is present), which is hypothesized by multiple existing
      theories of learning, participants would also learn from transitions - how the
      cues and effect change over time (e.g., a cue turns on and the effect turns on).
      We found that participants were better able to identify positive and negative
      cues in an environment in which only one cue changed from one trial to the next,
      compared to multiple cues changing (Experiments 1A, 1B). Within a single learning
      sequence, participants were also more likely to update their beliefs about causal
      strength when one cue changed at a time ('one-change transitions') than when
      multiple cues changed simultaneously (Experiment 2). Furthermore, learning was
      impaired when the trials were grouped by the state of the effect (Experiment 3)
      or when the trials were grouped by the state of a cue (Experiment 4), both of
      which reduce the number of one-change transitions. We developed a modification of
      the Rescorla-Wagner algorithm to model this 'Informative Transitions' learning
      processes.

PMID- 29358096
TI  - Corrigendum to "The impact of alcohol policies on alcohol-attributable diseases
      in Taiwan-A population-based study" [Drug Alcohol Depend. 180 (2017) 103-112].

PMID- 29358095
TI  - Synergistic antitumor effect of combined paclitaxel with FEN1 inhibitor in
      cervical cancer cells.
AB  - Studies on cervical cancer are urgently required to improve clinical outcomes. As
      a major anticancer drug for cervical cancer, paclitaxel has been used for many
      years in clinical therapy but its therapeutic efficacy is limited by common
      obstacle from cancer cells. The enhanced DNA repair pathways of cancer cells have
      been proved to survive DNA damage induced by chemotherapeutic drug. Inhibitors of
      specific DNA repair pathway can sensitize cancer cells to the treatment of
      chemotherapeutic drugs. In this paper we found that the effect of paclitaxel can
      be significantly improved when used in combination with FEN1 inhibitor SC13,
      suggesting a synergistic mechanism between the two compounds. Our studies suggest
      that FEN1 inhibition could be a novel strategy of tumor-targeting therapy for
      cervical cancer. Our work also revealed that paclitaxel demonstrates stronger
      synergistic effect with SC13 than other common used chemical drugs such as
      doxorubicin, carboplatin or camptothecin on cervical cancer cells.

PMID- 29358097
TI  - The effect of 5-HTTLPR and a serotonergic multi-marker score on amygdala,
      prefrontal and anterior cingulate cortex reactivity and habituation in a large,
      healthy fMRI cohort.
AB  - Major depressive disorder (MDD) is characterized by low mood for at least two
      weeks. Impaired emotion regulation has been suggested to be the consequence of
      dysfunctional serotonergic regulation of limbic and prefrontal regions,
      especially the amygdala, the anterior cingulate cortex (ACC) and the prefrontal
      cortex (PFC). The impact of genetic variation on brain function can be
      investigated with intermediate phenotypes. A suggested intermediate phenotype of
      MDD is emotion recognition: The 5-HTTLPR polymorphism of SLC6A4 as well as other
      serotonergic genes have been associated with amygdala and prefrontal function
      during emotion recognition. Previously, it has been suggested that habituation is
      a more reliable index of emotion recognition than functional activation. We
      examined the relationship of genes involved in serotonergic signaling with
      amygdala as well as prefrontal functional activation and habituation during an
      emotion recognition task in 171 healthy subjects. While effects of 5-HTTLPR and
      of a serotonergic multi-marker score (5-HTTLPR, TPH1(rs1800532), TPH2(rs4570625),
      HTR1A(rs6295) and HTR2A(rs6311)) on amygdala activation did not withstand
      correction for multiple regions of interest, we observed a strong correlation of
      the multi-marker score and habituation in the amygdala, DLPFC, and ACC. We
      replicated a well-studied intermediate phenotype for association with 5-HTTLPR
      and provided additional evidence for polygenic involvement. Furthermore, we
      showed that task habituation may be influenced by genetic variation in
      serotonergic signaling, particularly by a serotonergic multi-marker score. We
      provided preliminary evidence that PFC activation is an important intermediate
      phenotype of MDD. Future studies are needed to corroborate the results in larger
      samples.

PMID- 29358098
TI  - X-ray Computed Microtomography technique applied for cementitious materials: A
      review.
AB  - The main objective of this article is to present a bibliographical review about
      the use of the X-ray microtomography method in 3D images processing of
      cementitious materials microstructure, analyzing the pores microstructure and
      connectivity network, enabling tthe possibility of building a relationship
      between permeability and porosity. The use of this technique enables the
      understanding of physical, chemical and mechanical properties of cementitious
      materials by publishing good results, considering that the quality and quantity
      of accessible information were significant and may contribute to the study of
      cementitious materials development.

PMID- 29358099
TI  - Effects of nerve stimulation on amphibian oviductal activity.
AB  - The present study describes, for the first time in an anuran amphibian, the nerve
      stimulation effects on the secretory and motor activity of the oviduct of adult
      females. The results reveal that in Rhinella arenarum oviducts, the epithelial
      and glandular secretory cells of the mucosa of the pars convoluta respond to
      nerve stimulation secreting the products synthetized and stored in their
      cytoplasm. The ultrastructural analysis showed that the cell content released is
      made up of granular, fibrillar and floccular material, exocytosis being the main
      secretory mechanism found in epithelial secretory cells, although apocrine and
      holocrine processes could also be observed. In contrast, in glandular cells only
      exocytosis processes were found. With respect to the participation of the nervous
      system in the motility of the duct, observations under our experimental
      conditions indicated that oviductal nerve stimulation promotes motor activity as
      manifested by a succession of coordinated contractions and relaxations that
      generate movements similar to peristaltic waves. These results were observed in
      oviducts from animals captured during the reproductive and post reproductive
      periods. However, it is important to note that both the secretory response and
      duct motility are markedly decreased during the post reproductive period of the
      species.

PMID- 29358100
TI  - Juvenile myoclonic epilepsy and sleep.
AB  - Juvenile myoclonic epilepsy (JME) is a sleep-related epilepsy syndrome, and only
      a few studies have addressed the relationship between JME and sleep disorders. In
      this review, the sleep characteristics of patients with JME were summarized based
      on the features of circadian rhythm, the possible cause of the early morning
      seizures, the common subjective and objective sleep disorders, the alterations in
      sleep architecture, and the effect of sleep deprivation and sodium valproate
      (VPA). The aims of this study were to summarize the interaction between JME and
      sleep, to reveal JME sleep characteristics, to encourage clinicians to focus on
      JME and sleep, to heighten the positive diagnosis rate, to guide the treatment,
      to improve the prognosis, and to enhance the daily life quality of patients with
      JME. At the same time, this study aimed to present existing controversies, in
      order to necessitate further studies.

PMID- 29358101
TI  - The validity and reliability of the Arabic version of the Confusion Assessment
      Method for the Intensive Care Unit (CAM-ICU): A prospective cohort study.
AB  - BACKGROUND: Accurate diagnosis for Arabic speaking critically ill patients
      suffering from delirium is limited by the need for a valid/reliable translation
      of a standardized delirium instrument such as the Confusion Assessment Method for
      the ICU (CAM-ICU). OBJECTIVE: To determine the validity and reliability of the
      Arabic version of the CAM-ICU. DESIGN: A prospective cohort study design was used
      to conduct the current study. SETTINGS: Data collection took place in Geriatric,
      Emergency and Surgical intensive care units. PARTICIPANTS: Fifty-eight adult
      patients met the inclusion criteria and participated in the study. Among the
      participants 22(38%) patients were on mechanical ventilation. METHODS: After
      translating the CAM-ICU into Arabic language, the Arabic CAM-ICU was administered
      by two well-trained critical care nurses and compared with reference standard
      assessments by delirium experts using the Diagnostic and Statistical Manual of
      Mental Disorders, 4th Edition, Text Revision (DSM -IV-TR), along with assessment
      of severity of illness using Sequential Organ Failure Assessment (SOFA).
      Concurrent validity was assessed by calculating sensitivity, specificity and
      positive and negative predictive value (PPV and NPV) for the two Arabic CAM-ICU
      raters, where calculations were based on considering the DSM-IV-TR criterion as
      the reference standard. The convergent validity of the Arabic CAM-ICU was
      explored by comparing the Arabic CAM-ICU ratings and the total score of SOFA
      (severity of illness) and MMSE (cognitive impairment). RESULTS: A total of 58 ICU
      patients were included, of whom 27 (47%) were diagnosed with delirium during
      their ICU stay via DSM-IV criteria. Interrater reliability for the Arabic CAM
      ICU, overall and for mechanically ventilated patients assessed using Cohen's
      kappa (kappa) were 0.82 and 1, respectively, p < 0.001. The sensitivities (95%
      CI) for the two critical care nurses when using the Arabic CAM-ICU compared with
      the reference standard were 81% (60%-93%) and 85% (65%-95%), respectively,
      whereas specificity (95% CI) was 81%(62%-92%) for both nurses. High sensitivity
      and specificity measures were also observed across subgroups; 100% for
      mechanically ventilated patients, 88% (60%-98%) and 79% (49%-94%) for those aged
      65 years or older and 82% (56%-95%) and 75% (43%-93%) for those with SOFA scores
      at or above the median value. CONCLUSIONS: The Arabic CAM-ICU appeared to be
      valid and reliable tool for diagnosing delirium. Future investigations may lead
      to a better understanding of the prevalence, predictors, and consequences of
      delirium among critically ill Arabic speaking patients.

PMID- 29358102
TI  - Social cognition intervention in schizophrenia: Description of the training of
      affect recognition program - Indian version.
AB  - Social cognition refers to mental operations involved in processing of social
      cues and includes the domains of emotion processing, Theory of Mind (ToM), social
      perception, social knowledge and attributional bias. Significant deficits in ToM,
      emotion perception and social perception have been demonstrated in schizophrenia
      which can have an impact on socio-occupational functioning. Intervention modules
      for social cognition have demonstrated moderate effect sizes for improving
      emotion identification and discrimination. We describe the Indian version of the
      Training of Affect Recognition (TAR) program and a pilot study to demonstrate the
      feasibility of administering this intervention program in the Indian population.
      We also discuss the cultural sensibilities in adopting an intervention program
      for the Indian setting. To the best of our knowledge this is the first
      intervention program for social cognition for use in persons with schizophrenia
      in India.

PMID- 29358103
TI  - Application of stacked convolutional and long short-term memory network for
      accurate identification of CAD ECG signals.
AB  - Coronary artery disease (CAD) is the most common cause of heart disease globally.
      This is because there is no symptom exhibited in its initial phase until the
      disease progresses to an advanced stage. The electrocardiogram (ECG) is a widely
      accessible diagnostic tool to diagnose CAD that captures abnormal activity of the
      heart. However, it lacks diagnostic sensitivity. One reason is that, it is very
      challenging to visually interpret the ECG signal due to its very low amplitude.
      Hence, identification of abnormal ECG morphology by clinicians may be prone to
      error. Thus, it is essential to develop a software which can provide an automated
      and objective interpretation of the ECG signal. This paper proposes the
      implementation of long short-term memory (LSTM) network with convolutional neural
      network (CNN) to automatically diagnose CAD ECG signals accurately. Our proposed
      deep learning model is able to detect CAD ECG signals with a diagnostic accuracy
      of 99.85% with blindfold strategy. The developed prototype model is ready to be
      tested with an appropriate huge database before the clinical usage.

PMID- 29358104
TI  - The association of discharge destination with 30-day rehospitalization rates
      among older adults receiving lumbar spinal fusion surgery.
AB  - BACKGROUND: As defined by Medicare (United States), post-acute rehabilitation
      services include care provided in inpatient rehabilitation units and facilities,
      skilled nursing facilities, long-term acute hospitals, and by home health
      services. METHODS: We retrospectively evaluated the use of rehabilitation-based
      post-acute services among Medicare beneficiaries who were hospitalized for lumbar
      spinal fusion (ICD-9-CM procedure codes 81.04-81.08) in 2012-2014, examined the
      case-mix for those discharged to rehabilitation- and non-rehabilitation based
      services, and determined the association between these categories of discharge
      disposition and 30-day rehospitalization. The independent effect of
      rehabilitation-based discharge destination on 30-day readmissions was examined
      with a generalized linear mixed model, first adjusting for patient
      characteristics and then stratified by clusters that delineated more homogenous
      clinical profiles. RESULTS: Among 261,558 Medicare beneficiaries with lumbar
      spinal fusion surgery, 50.8% were discharged to a rehabilitation-based post-acute
      services. Patients discharged to rehabilitation-based services were older and had
      more comorbidities, and had longer hospital lengths of stays. After adjusting for
      patient and hospital characteristics, patients discharged to rehabilitation-based
      post-acute care had increased odds of 30-day rehospitalization than those without
      discharge to other destinations (OR 1.36; 95%CI = 1.31, 1.40). Analysis of
      patients by clinical profile clusters found similar results. CONCLUSIONS:
      Clinical profiles of Medicare beneficiaries who had lumbar spinal fusion surgery
      and were discharged to rehabilitation-based post-acute services included more
      comorbidities than those discharged to non-rehabilitation based settings.
      Controlling for these differences did not mediate the negative association
      between use of rehabilitation-based post-acute services and 30-day readmission.

PMID- 29358105
TI  - Using real-time ultrasound imaging as adjunct teaching tools to enhance physical
      therapist students' ability and confidence to perform traction of the knee joint.
AB  - Often, physical therapy students struggle with the skill and the confidence to
      perform manual techniques for musculoskeletal examination. Current teaching
      methods lack concurrent objective feedback. Real-time ultrasound imaging (RTUI)
      has the advantage of generating visualization of anatomical structures in real
      time in an efficient and safe manner. We hypothesize that the use of RTUI to
      augment teaching with concurrent objective visual feedback will result in
      students' improved ability to create a change in joint space when performing a
      manual knee traction and higher confidence scores. Eighty-six students were
      randomly allocated to a control or an experimental group. All participants
      received baseline instructions on how to perform knee traction. The control group
      received standardized lab instruction (visual, video, and instructor/partner
      feedback). The experimental group received standardized lab instruction augmented
      with RTUI feedback. Pre-data and post-data collection consisted of measuring
      participants' ability to create changes in joint space when performing knee
      traction, a confidence survey evaluating perceived ability and a reflection
      paper. Joint space changes between groups were compared using a paired t-test.
      Surveys were analyzed with descriptive statistics and compared using Wilcoxon
      Rank Sum and for the reflection papers, themes were identified and descriptive
      statistics reported. Although there were no statistically significant differences
      between the control and the experimental group, overall scores improved.
      Qualitative data suggests students found the use of ultrasound imaging beneficial
      and would like more exposure. This novel approach to teaching knee traction with
      RTUI has potential and may be a basis for further studies.

PMID- 29358106
TI  - The stereotactic suboccipitaltranscerebellar approach to lesions of the brainstem
      and the cerebellum.
AB  - OBJECTIVE: The stereotactic suboccipital-transcerebellar approach is widely
      regarded as technically demanding requiring substantial modifications of the
      standard stereotactic methods thus often making a transfrontal approach
      preferable. In this comprehensive series we aim to present our experience with
      the stereotactic suboccipital-transcerebellar approach to lesions of the
      brainstem or cerebellum using two standard stereotactic systems. PATIENTS AND
      METHODS: In the period of 2000-2015 overall 80 patients (mean age 43.95 +/- 23.76
      years) with lesions of the brainstem or cerebellum underwent stereotactic surgery
      for diagnostic or therapeutic purposes via a suboccipital approach. In 59
      patients stereotactic surgery was performed using the Riechert-Mundinger
      Stereotactic Frame, the Leksell Stereotactic Frame was used in 21 patients. For
      both frames standard systems were used without modification. Retrospective
      analysis of intraoperative stereotactic technique, achievement of the predefined
      surgical objectives and perioperative complications was carried out. RESULTS: In
      this series, the stereotactic suboccipital-transcerebellar approach proved to be
      feasible with two standard stereotactic systems. Using either frame the
      predefined surgical objective was achieved in 90.0%. A verified neuropathological
      diagnosis was obtained in 89.6%. Minor transient perioperative complications
      occurred in 8.75%. There was no surgery-related permanent morbidity or mortality.
      CONCLUSION: In this comprehensive series the stereotactic suboccipital
      transcerebellar approach using a standard stereotactic system proved to be a
      favorable stereotactic approach with a high diagnostic success rate and no
      surgery-related permanent morbidity.

PMID- 29358107
TI  - The oxymoron of image-guided resection in 3 T MRI-negative extratemporal
      epilepsy: Technique and postoperative results.
AB  - OBJECTIVE: We share our experience with extratemporal MRI-negative epilepsies
      that received "image-guided" resection with the use of neuronavigation after
      invasive presurgical video-EEG monitoring. We describe and discuss our technique
      of image generation, navigation system registration, and surgical resection. In
      addition, we evaluate seizure outcome with respect to the preoperatively planned
      versus achieved resection. PATIENTS AND METHODS: Seven patients with 3 T MRI
      negative extratemporal epilepsy received navigation-guided resective surgery. The
      resection plan was based on electrophysiological data from intracranial EEG
      recordings. For each case a resection segment was created in the neuronavigation
      device in a systematic manner. We compared the preoperatively planned segment to
      the achieved resection and looked for correlation with postoperative seizure
      outcome according to Engel classification, at last follow-up (mean 2.4 years,
      range 1-4 years). RESULTS: Mean volume of planned resections was 23.8 +/- 15.3
      cm3 and of achieved resections 17 +/- 10.4 cm3. There was complete overlap with
      planned resection in 4 patients and partial overlap in 3. Postoperative seizure
      outcome was class I in 4 patients (57%), IIIA in 1 patient and IVB in 2 patients.
      Three patients reached seizure-freedom (Engel IA). Volume of planned resection,
      volume difference of planned versus achieved resection and level of overlap
      (complete versus partial) did not significantly correlate to seizure outcome.
      CONCLUSION: The use of neuronavigation for planning and executing a tailored
      resection in MRI-negative extratemporal epilepsy is elaborate but can be an
      effective procedure.

PMID- 29358108
TI  - Increased PT/SS may play an important role in the pathogenesis of lumbar
      spondylolisthesis with degenerative lumbar scoliosis.
AB  - OBJECTIVE: To explore the clinical and spinopelvic features in patients with
      lumbar spondylolisthesis and degenerative lumbar scoliosis (LSDLS) and those with
      standalone lumbar spondylolisthesis (SALS). PATIENTS AND METHODS: We
      retrospectively analyzed 130 patients with lumbar spondylolisthesis seen between
      05/2013 and 12/2016 in our hospital. Propensity score matching was used to reduce
      an age distribution imbalance between the two groups. Clinical and spinopelvic
      parameters were compared by independent samples t test and chi-square test.
      Nonlinear binary logistic regression analysis was used to analyze the independent
      factors. RESULTS: There was no significant difference between groups for body
      mass index, level of intercrest line, level of spondylolisthesis, grade of
      spondylolisthesis, sagittal translation, segmental angulation, thoracic kyphosis,
      or sagittal vertical axis. The LSDLS group had significantly lower lumbar
      lordosis (LL) than the SALS group. The LSDLS group showed significantly greater
      pelvic tilt (PT) and ratio of PT to SS (sacral slope) (PT/SS), and lower SS. The
      pelvic incidence (PI) was not significantly different. The LSDLS group showed
      stronger significant differences in PT/SS compared to the SALS group. With each
      0.1 increase in PT/SS, the risk of LSDLS increased 1.465 times. CONCLUSIONS:
      Patients with spondylolysis are less prone to development of DLS. Lower LL and
      SS, and higher PT are associated with the occurrence of LSDLS. Increased PT/SS
      may play an important role in the pathogenesis of LSDLS.

PMID- 29358109
TI  - DEEPAligner: Deep encoding of pathways to align epigenetic signatures.
AB  - BACKGROUND AND OBJECTIVE: Recently, differential DNA Methylation is known to
      affect the regulatory mechanism of biological pathways. A pathway encompasses a
      set of interacting genes or gene products that altogether perform a given
      biological function. Pathways often encode strong methylation signatures that are
      capable of distinguishing biologically distinct subtypes. Even though Next
      Generation Sequencing techniques such as MeDIP-seq and MBD-isolated genome
      sequencing (MiGS) allow for genome-wide identification of clinical and biological
      subtypes, there is a pressing need for computational methods to compare
      epigenetic signatures across pathways. METHODS: A novel alignment method, called
      DEEPAligner (Deep Encoded Epigenetic Pathway Aligner), is proposed in this paper
      that finds functionally consistent and topologically sound alignments of
      epigenetic signatures from pathway networks. A deep embedding framework is used
      to obtain epigenetic signatures from pathways which are then aligned for
      functional consistency and local topological similarity. RESULTS: Experiments on
      four benchmark cancer datasets reveal epigenetic signatures that are conserved in
      cancer-specific and across-cancer subtypes. CONCLUSION: The proposed deep
      embedding framework obtains highly coherent signatures that are aligned for
      biological as well as structural orthology. Comparison with state-of-the-art
      network alignment methods clearly suggest that the proposed method obtains
      topologically and functionally more consistent alignments. AVAILABILITY:
      http://bdbl.nitc.ac.in/DEEPAligner.

PMID- 29358110
TI  - Unwanted ventilatory alarm: Be careful about flow sensors size.

PMID- 29358111
TI  - Simultaneous surface and depth neural activity recording with graphene transistor
      based dual-modality probes.
AB  - Subdural surface and penetrating depth probes are widely applied to record neural
      activities from the cortical surface and intracortical locations of the brain,
      respectively. Simultaneous surface and depth neural activity recording is
      essential to understand the linkage between the two modalities. Here, we develop
      flexible dual-modality neural probes based on graphene transistors. The neural
      probes exhibit stable electrical performance even under 90 degrees  bending
      because of the excellent mechanical properties of graphene, and thus allow multi
      site recording from the subdural surface of rat cortex. In addition, finite
      element analysis was carried out to investigate the mechanical interactions
      between probe and cortex tissue during intracortical implantation. Based on the
      simulation results, a sharp tip angle of pi/6 was chosen to facilitate tissue
      penetration of the neural probes. Accordingly, the graphene transistor-based dual
      modality neural probes have been successfully applied for simultaneous surface
      and depth recording of epileptiform activity of rat brain in vivo. Our results
      show that graphene transistor-based dual-modality neural probes can serve as a
      facile and versatile tool to study tempo-spatial patterns of neural activities.

PMID- 29358112
TI  - Biosensors for rapid and sensitive detection of Staphylococcus aureus in food.
AB  - Foodborne illness outbreaks caused by the consumption of food contaminated with
      harmful bacteria has drastically increased in the past decades. Therefore,
      detection of harmful bacteria in the food has become an important factor for the
      recognition and prevention of problems associated with food safety and public
      health. Staphylococcus aureus is one of the most commonly isolated foodborne
      pathogen and it is considered as a major cause of foodborne illnesses worldwide.
      A number of different methods have been developed for the detection and
      identification of S. aureus in food samples. However, some of these methods are
      laborious and time-consuming and are not suitable for on-site applications.
      Therefore, it is highly important to develop rapid and more approachable
      detection methods. In the last decade, biosensors have gained popularity as an
      attractive alternative method and now considered as one of most rapid and on-site
      applicable methods. An overview of the biosensor based methods used for the
      detection of S. aureus is presented herein. This review focuses on the state-of
      the-art biosensor methods towards the detection and quantification of S. aureus,
      and discusses the most commonly used biosensor methods based on the transducing
      mode, such as electrochemical, optical, and mass-based biosensors.

PMID- 29358113
TI  - Long term exposure to low dose neurotoxic pesticides affects hatching, viability
      and cholinesterase activity of Artemia sp.
AB  - The brine shrimp Artemia was used as a model organism to test toxicity of several
      neuroactive pesticides (chlorpyrifos (CLP), chlorpyrifos oxon (CLP ox), diazinon
      (DZN), carbaryl (CBR)) following exposure to far below than lethal doses. Cysts
      were exposed to the pesticides in order to test a scenario similar to actual
      coastal environment contamination, by analyzing different responses. Cysts were
      rehydrated in water containing the pesticides at concentrations ranging from 10
      11 to 10-5 M, for 72, 96 and 192 h, respectively. For these exposure times,
      morpho-functional and biochemical parameters, such as hatching speed and
      viability were investigated in the larvae together with cholinesterase (ChE)
      activity quantification and histochemical localization. Finally, ChE inhibition
      was also compared with conventional selective ChE inhibitors. Results showed that
      CLP ox and CBR caused a significant dose-dependent decrease in hatching speed,
      followed by high percentages of larval death, while CLP and DZN were responsible
      for irregular hatching patterns. In addition, the pesticides mostly caused larval
      death some days post-hatching, whereas this effect was negligible for the
      specific ChE inhibitors, suggesting that part of pesticide toxicity may be due to
      molecules other than the primary target. ChE activity was observed in the
      protocerebrum lobes, linked to the development of pair eyes. Such activity was
      inhibited in larvae exposed to all pesticides. When compared to conventional
      selective inhibitors of ChE activities, this inhibition demonstrated that the
      selected pesticides mainly affect acetylcholinesterase and, to a lesser extent,
      pseudocholinesterases. In conclusion, the brine shrimp is a good model to test
      the environmental toxicity of long term exposure to cholinergic pesticides, since
      changes in hatching speed, viability and ChE activity were observed.

PMID- 29358114
TI  - Expression of flavivirus capsids enhance the cellular environment for viral
      replication by activating Akt-signalling pathways.
AB  - Flaviviruses depend on multiple host pathways during their life cycles and have
      evolved strategies to avoid the innate immune response. Previously, we showed
      that the West Nile virus capsid protein plays a role in this process by blocking
      apoptosis. In this study, we examined how expression of capsid proteins from
      several flaviviruses affects apoptosis and other host processes that impact virus
      replication. All of the tested capsid proteins protected cells from Fas-dependent
      apoptosis through a mechanism that requires activated Akt. Capsid expression
      upregulated other Akt-dependent cellular processes including expression of
      glucose transporter 1 and mitochondrial metabolism. Protein phosphatase 1, which
      is known to inactivate Akt, was identified as a DENV capsid interacting protein.
      This suggests that DENV capsid expression activates Akt by sequestering
      phosphatases that downregulate phospho-Akt. Capsid-dependent upregulation of Akt
      would enhance downstream signalling pathways that affect cell survival and
      metabolism, thus providing a favourable environment for virus replication.

PMID- 29358115
TI  - Long-term exposure to residential green and blue spaces and anxiety and
      depression in adults: A cross-sectional study.
AB  - BACKGROUND: Although exposure to natural outdoor environments has been
      consistently associated with improved perceived general health, available
      evidence on a protective association between this exposure and specific mental
      health disorders such as depression and anxiety is still limited. OBJECTIVE: The
      aim of this study was to evaluate the effects of long-term exposure to
      residential green and blue spaces on anxiety and depression and intake of related
      medication. Additionally, we aimed to explore potential mediators and effect
      modifiers of this association. METHODS: The study was based on an existing adult
      cohort (ALFA - Alzheimer and Families) and includes 958 adult participants from
      Barcelona recruited in 2013-2014. For each participant residential green and blue
      exposure indicators [surrounding greenness (NDVI), amount of green (land-cover)
      and access to major green spaces and blue spaces] were generated for different
      buffers (100m, 300m and 500m). Participants reported their history of doctor
      diagnosed anxiety and depressive disorders and intake of related medication.
      Logistic regression models were applied to assess the corresponding associations.
      RESULTS: Increasing surrounding greenness was associated with reduced odds of
      self-reported history of benzodiazepines [e.g. Odds ratio - OR (95%CI) = 0.62
      (0.43, 0.89) for 1-interquartile range (IQR) increase in NDVI in a 300m buffer]
      and access to major green spaces was associated with self-reported history of
      depression [OR (95%CI) = 0.18 (0.06, 0.58)]. No statistically significant
      associations were observed with blue spaces. Air pollution (between 0.8% and
      29.6%) and noise (between 2.2% and 5.3%) mediated a proportion of the
      associations observed, whereas physical activity and social support played a
      minor role. CONCLUSION: Our findings suggest a potential protective role of green
      spaces on mental health (depression and anxiety) in adults, but further studies,
      especially longitudinal studies, are needed to provide further evidence of these
      benefits and of the mediation role of exposures like air pollution and noise.

PMID- 29358116
TI  - Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta
      analysis of epidemiologic studies.
AB  - Cadmium has been proposed to be the one of the factors of atherosclerosis
      development, although the existing data are still controversial. The primary
      objective of the present study is the review and the meta-analysis of studies
      demonstrating the association between Cd exposure and atherosclerosis as well as
      review of the potential mechanisms of such association. We performed a systematic
      search in the PubMed-Medline database using the MeSH terms cadmium,
      cardiovascular disease, atherosclerosis, coronary artery disease, myocardial
      infarction, stroke, mortality and humans up through December 20, 2017. Elevated
      urinary Cd levels were associated with increased mortality for cardiovascular
      disease (HR = 1.34, 95% CI: 1.07-1.67) as well as elevated blood Cd levels (HR =
      1.78, 95% CI: 1.24-2.56). Analysis restricted to never smokers showed similar,
      though more imprecise, results. Consistently, we also observed an association
      between Cd exposure markers (blood and urine) and coronary heart disease, stroke,
      and peripheral artery disease. Moreover, Cd exposure was associated with
      atherogenic changes in lipid profile. High Cd exposure was associated with higher
      TC levels (OR = 1.48, 95% CI: 1.10-2.01), higher LDL-C levels (OR = 1.31, 95% CI
      0.99-1.73) and lower HDL-C levels (OR = 1.96, 95% CI: 1.09-3.55). The mechanisms
      of atherogenic effect of cadmium may involve oxidative stress, inflammation,
      endothelial dysfunction, enhanced lipid synthesis, up-regulation of adhesion
      molecules, prostanoid dysbalance, as well as altered glycosaminoglycan synthesis.

PMID- 29358118
TI  - Polygenic risk for Alzheimer's disease influences precuneal volume in two
      independent general populations.
AB  - Alzheimer's disease (AD) is heritable with complex genetic underpinnings. Based
      on previous results from large-scale genome-wide association studies, recent
      studies found an association between the polygenic risk score (PGRS) of AD and
      the structure of some preselected brain regions, but the effects of AD PGRS on
      all voxels of the brain have not been fully investigated. In the present study,
      we examined the voxel-wise effect of AD PGRS on the entire brain and the
      influence of AD PGRS on cognitive function in 2 independent healthy young
      cohorts. In both cohorts, an elevated AD PGRS was associated with a smaller
      precuneal volume, and the effect remained after excluding the APOE genotype. No
      correlation was found between AD PGRS and any cognitive measure in either sample.
      Finding a negative correlation between the AD PGRS and the precuneal volume could
      help to elucidate the mechanism of the genetic risk for AD and could provide a
      potential biomarker for early detection and possible interventions in AD.

PMID- 29358117
TI  - The effect of Alzheimer's disease on spatial navigation strategies.
AB  - Hippocampal and basal forebrain (BF) atrophy is associated with allocentric
      navigation impairment in Alzheimer's disease (AD) and may lead to recruitment of
      compensatory navigation strategies. We examined navigation strategy preference,
      its association with allocentric navigation, and the role of hippocampal and BF
      volumes in this association in early clinical stages of AD. Sixty nine
      participants-amnestic mild cognitive impairment (aMCI) due to AD (n = 28), AD
      dementia (n = 21), and cognitively normal (CN) older adults (n = 20)-underwent
      virtual Y-maze strategy assessment, real-space navigation testing, cognitive
      assessment, and hippocampal and BF volumetry. Preference for egocentric over
      allocentric strategy increased with AD severity (aMCI: 67% vs. 33%; dementia: 94%
      vs. 6%), which contrasted with preference in the CN group (39% vs. 61%). Those
      with aMCI who preferred egocentric strategy had worse allocentric navigation.
      Among those with aMCI, hippocampal and BF atrophy explained up to 25% of the
      association between strategy preference and allocentric navigation. The
      preference for egocentric strategy in AD may reflect recruitment of compensatory
      extrahippocampal navigation strategies as adaptation to hippocampal and BF
      neurodegeneration.

PMID- 29358119
TI  - Low subjective socioeconomic status stimulates orexigenic hormone ghrelin - A
      randomised trial.
AB  - Recent evidence suggests that lower perceived socioeconomic status is linked to
      increased appetite and intake of greater calories. Yet, whether insecurity of
      socioeconomic resources directly influences regulatory systems of appetite and
      energy intake is not known. Considering psychological states, mindsets and
      beliefs have shown to meaningfully affect physiological responses to food, the
      present study tested the hypothesis that low subjective socioeconomic status
      (SSS) will have a direct influence on physiological responses, such as appetite
      related hormones (ghrelin, pancreatic polypeptide and insulin). Forty-eight
      healthy males were randomly (crossover, counterbalanced) assigned, to two
      experimental conditions where participants were either experimentally induced to
      feel low SSS or not (control; CON). Feelings of low SSS resulted in an increase
      in active ghrelin (an orexigenic hormone) following the SSS manipulation compared
      with baseline, while no change in active ghrelin was observed in CON.
      Furthermore, participants reported lower fullness and satiety following low SSS
      compared with CON. Our findings demonstrate that SSS may influence hunger
      regulation and appetite, and suggest that physiological systems regulating energy
      balance (i.e. caloric resources) may also be sensitive to perceived deprivation
      or imbalances in critical non-food resources (socioeconomic resources).

PMID- 29358120
TI  - Hair cortisol concentrations in war-affected adolescents: A prospective
      intervention trial.
AB  - Temporal examinations of the biological signature of stress or trauma in war
      affected populations are seldom undertaken. Moreover, few studies have examined
      whether stress biomarkers track biological sensitivity to brief interventions
      targeting the improvement of psychosocial wellbeing. Our study is the first to
      prospectively examine, in war-affected adolescents, the associations between hair
      cortisol concentrations (HCC) and self-reports of stress, insecurity,
      posttraumatic reactions, and lifetime trauma. We conducted a randomized
      controlled trial to test the impact of an 8-week intervention based on profound
      stress attunement. We collected data for a gender-balanced sample of 733 Syrian
      refugee (n = 411) and Jordanian non-refugee (n = 322) adolescents (12-18 years),
      at three time-points. We used growth mixture models to classify cortisol
      trajectories, and growth models to evaluate intervention impact on stress
      physiology. We observed three trajectories of HCC: hypersecretion, medium
      secretion, and hyposecretion (9.6%, 87.5% and 2.9% of the cohort, respectively).
      For every one percent increase in levels of insecurity, adolescents were 0.02
      times more likely to have a trajectory of hypersecretion (95% CI: 1.00, 1.03, p =
      0.01). For each additional symptom of posttraumatic stress reported, they were
      0.07 times less likely to show hyposecretion (95% CI: 0.89, 0.98, p = 0.01).
      Indeed, stronger posttraumatic stress reactions were associated with a pattern of
      within-individual cortisol dysregulation and medium secretion. Overall, HCC
      decreased by a third in response to the intervention (95% CI: -0.19, -0.03, p =
      0.01). While the intervention decreased HCC for youth with hypersecretion and
      medium secretion, it increased HCC for youth with hyposecretion (95% CI: 0.22,
      1.16, p = 0.004), relative to controls. This suggests a beneficial regularization
      of cortisol levels, corroborating self-reports of improved psychosocial
      wellbeing. We did not find evidence to suggest that gender, resilience, or
      posttraumatic stress disorder influenced the strength or direction of responses
      to the intervention. This robust impact evaluation exemplifies the utility of
      biomarkers for tracking physiological changes in response to interventions over
      time. It enhances the understanding of trajectories of endocrine response in
      adverse environments and patterns of stress responsivity to ecological
      improvement.

PMID- 29358122
TI  - Risk factors for child neglect: A meta-analytic review.
AB  - Knowledge of risk factors and their effects is vital for successfully preventing
      and reducing child neglect. This study provides a meta-analytic update of
      research on risk factors for child neglect. A total of 315 effect sizes were
      extracted from 36 primary studies and classified into 24 risk domains. Effects of
      15 risk domains were significant and ranged from small (r = .110) to large (r =
      .372) in magnitude. Most risks were found at the parental level, such as having a
      history of antisocial behavior/criminal offending (r = .372); having a history of
      mental/psychiatric problems (r = . 259); having mental/physical problems (r =
      .207); and experiences of abuse in own childhood (r = .182). The effect of mother
      related risk factors was not significantly different from the effect of father
      related risk factors. It is concluded that child neglect is determined by
      multiple risk domains and that especially parent-related risk factors are
      important in preventing and reducing child neglect. Implications of the results
      for clinical practice are discussed.

PMID- 29358121
TI  - Psychological and physical intimate partner violence and young children's mental
      health: The role of maternal posttraumatic stress symptoms and parenting
      behaviors.
AB  - Young children are at significant risk of exposure to intimate partner violence
      (IPV), and vulnerable to exposure-related psychopathology, yet few studies
      investigate the effects of exposure to IPV on children under the age of 5 years.
      The current study investigated the role of maternal PTSD symptoms and parenting
      strategies in the relationship between mothers' IPV experiences and
      psychopathology in their young children, ages 3-6 years in a community-based
      cohort of 308 mother-child dyads at high risk for family violence. Data were
      collected from 2011 to 2014. IPV history and maternal PTSD symptoms were assessed
      by self-report questionnaires. Children's symptoms were assessed with a
      developmentally-sensitive psychiatric interview administered to mothers.
      Punitive/restrictive parenting was independently-coded from in-depth interviews
      with mothers about their disciplinary practices. Hypothesized direct and indirect
      pathways between physical and psychological IPV, maternal PTSD, maternal
      parenting style, and children's internalizing and externalizing symptoms were
      examined with mediation models. Results indicated that neither physical nor
      psychological IPV experienced by mothers was directly associated with children's
      symptoms. However, both types of victimization were associated with maternal PTSD
      symptoms. Examination of indirect pathways suggested that maternal PTSD symptoms
      mediated the relationship between mothers' psychological and physical IPV
      experiences and children's internalizing and externalizing symptoms and mothers'
      restrictive/punitive parenting mediated the relationship between mothers'
      psychological IPV and children's externalizing symptoms. In addition, there was a
      path from maternal physical IPV to child externalizing symptoms through both
      maternal PTSD symptoms and restrictive/punitive parenting. Findings highlight the
      importance of supporting parents in recovering from the sequelae of their own
      traumatic experiences, as their ensuing mental health symptoms and parenting
      behaviors may have a significant impact on their children's emotional health.

PMID- 29358123
TI  - Aggression and violence in healthcare and its impact on nursing students: A
      narrative review of the literature.
AB  - Aggression and violence is a significant social problem in many countries and an
      increasing problem in healthcare settings in which nurses are particularly
      vulnerable. The literature suggests that aggression and violence has a
      significant negative impact upon nurses and potentially upon nursing students and
      can result in these staff members experiencing stress as a direct result of these
      adverse events. The literature suggests that there is confusion over what
      constitutes aggression and violence in the workplace and therefore a true lack of
      understanding of the scale of the problem relating to nursing students. This
      review proposes that nursing students are indeed at significant risk of
      aggression and violence in the clinical setting which has the potential to
      significantly impact their role as a novice carer. Furthermore, aggression and
      violence can manifest negative stress responses in individuals, therefore, the
      potential for nursing students to cope with stressful situations shall be
      presented.

PMID- 29358125
TI  - Radiation induced in-situ cationic polymerization of polystyrene organogel for
      selective absorption of cholorophenols from petrochemical wastewater.
AB  - A new in-situ cationic polymerization was performed to synthesize a cross-linked
      (91%) polystyrene (PS) organogel through tetrachloroethylene radiolysis assisted
      by 60Co gamma rays. Hoernschemeyer diagram and swelling capacity test show a
      better selectivity of PS organogel to chlorinated molecules compared to ester,
      hydrocarbons and alcohols organic molecules by 80-184 folds. Response surface
      modeling (RSM) of CPs (2,4,6-trichlorophenol) sorption from artificial wastewater
      confirm superiority of PS organogel to absorb 1746 MUmol CPs/g (~345 mg CPs/g) at
      broad pH (4-10) and temperature (25-45  degrees C). Based on ANOVA statistic,
      simulated CPs absorption model onto PS organogel was successfully developed, with
      accuracy of prediction of R2~ RAdj2 of 0.991-0.995 and lower coefficient of
      variation of 2.73% with Fmodel of 611.4 at p < .0001. Particularly, the usage of
      PS organogel for petroleum wastewater reclamation exhibited higher absorption
      affinities for all the organic contaminants especially for CPs (>99%) by non
      covalent and/or dispersive interaction mechanisms with a well-term reusability
      and good stability up to 5 cycles.

PMID- 29358124
TI  - A2E-associated cell death and inflammation in retinal pigmented epithelial cells
      from human induced pluripotent stem cells.
AB  - Accumulation of lipofuscin in the retinal pigmented epithelium (RPE) is observed
      in retinal degenerative diseases including Stargardt disease and age-related
      macular degeneration. Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) is
      a major component of lipofuscin. A2E has been implicated in RPE atrophy and
      retinal inflammation; however, mice with A2E accumulation display only a mild
      retinal phenotype. In the current study, human iPSC-RPE (hiPSC-RPE) cells were
      generated from healthy individuals to examine effects of A2E in human RPE cells.
      hiPSC-RPE cells displayed RPE-specific features, which include expression of RPE
      specific genes, tight junction formation and ability to carry out phagocytosis.
      hiPSC-RPE cells demonstrated cell death and increased VEGF-A production in a time
      dependent manner when they were cocultured with 10MUM of A2E. PCR array analyses
      revealed upregulation of 26 and 12 pro-inflammatory cytokines upon A2E and H2O2
      exposure respectively, indicating that A2E and H2O2 can cause inflammation in
      human retinas. Notably, identified gene profiles were different between A2E- and
      H2O2- treated hiPSC-RPE cells. A2E caused inflammatory changes observed in
      retinal degenerative diseases more closely as compared to H2O2. Collectively,
      these data obtained with hiPSC-RPE cells provide evidence that A2E plays an
      important role in pathogenesis of retinal degenerative diseases in humans.

PMID- 29358126
TI  - Differential mobility spectrometry followed by tandem mass spectrometry with
      multiple ion monitoring for bioanalysis of eptifibatide in rat plasma.
AB  - Eptifibatide is a therapeutic cyclic peptide with poor collision-induced
      dissociation (CID) efficiency for multiple reaction monitoring (MRM), which
      limits the development of a traditional liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) bioassay with MRM. In this study, a method combining
      differential mobility spectrometry (DMS) with liquid chromatography-multiple ion
      monitoring (LC-DMS-MIM) was developed for the quantitation of eptifibatide in rat
      plasma. After solid phase extraction (SPE) of 100 MUL plasma on an Oasis(r) HLB
      cartridge, the analyte and I.S. (octreotide) were analyzed using a SCIEX QTRAP
      6500 operated in the positive ion mode and preceded by a DMS device. The lower
      limit of quantitation (LLOQ) for eptifibatide was 0.5 ng/mL using only 100 MUL
      plasma. The method was linear in the concentration range 0.5-300 ng/mL with good
      precision and accuracy. Compared to regulated quantitative LC-MS/MS bioanalysis
      of eptifibatide, the LC-DMS-MIM method effectively overcomes the sensitivity
      challenge in the LC-MRM method and reduces the high background noise and matrix
      interference in LC-MIM method without DMS. The method was successfully applied to
      a pharmacokinetic study involving intravenous injection of eptifibatide to Wistar
      rats.

PMID- 29358127
TI  - The role of curcumae rhizoma-sparganii rhizoma medicated serum in epithelial
      mesenchymal transition in the triple negative breast cancer: Pharmacological role
      of CR-SR in the TBNC.
AB  - The aim of this study was to investigate the effect of Curcumae Rhizoma-Sparganii
      Rhizoma (CR-SR) medicated serum on the changes of epithelial-mesenchymal
      transition (EMT) in the triple-negative breast cancer (TNBC). The EMT model was
      developed by using the TNBC MDA-MB-468 cells, which were treated with TGF-beta1.
      The migration and invasion abilities of TGF-beta1-treated MDA-MB-468 cells were
      detected by wound healing assay and transwell assay. Protein expression levels of
      E-cadherin and vimentin were determined by western blot. CR-SR medicated serum
      repressed the phenotypic transition in the TGF-beta1-induced MDA-MB-468 cells.
      Moreover, CR-SR medicated serum inhibited TGF-beta1-induced cell proliferation,
      migration and invasion. Besides, CR-SR medicated serum could reduce TGF-beta1
      induced up-regulation of the phosphorylation levels of Smad3, and reduce the
      expression of several transcription factors (Snail1, Snail2 and Twist1). CR-SR
      medicated serum might suppress TGF-beta1-induced EMT in TNBC by decreasing the
      phosphorylated Smad3 (p-Smad3) pathway in vitro.

PMID- 29358128
TI  - Transferrin and tocopheryl-polyethylene glycol-succinate dual ligands decorated,
      cisplatin loaded nano-sized system for the treatment of lung cancer.
AB  - Nanocarriers decorated with different ligands were used to achieve lung cancer
      treatment. Surface decoration of nanoparticulate system will assist in targeting
      the drug to specific tumor cells and tissues. The aim of this research was to
      develop a dual ligands decorated nanocarriers (NCs), which could increase the
      cell uptake and anti-tumor efficiency. Two different ligands: Transferrin (Tf)
      and D-alpha-tocopheryl polyethylene glycol succinate (TPGS) containing ligands
      were synthesized. Dual ligands decorated nanocarriers (DL-NCs) was constructed.
      The in vitro cytotoxicity, in vivo biodistribution, and in vivo antitumor
      efficacy of the DL-NCs were evaluated. DL-NCs can efficiently deliver cisplatin
      (CDDP) into lung cancer cells in vitro and reduced xenograft tumor size in vivo.
      The encapsulation of CDDP in the DL-NCs significantly improved the cytotoxicity
      and antitumor efficacy. DL-NCs held great potential for achieving an optimal
      therapeutic effect in the treatment of lung cancer.

PMID- 29358129
TI  - miR-1301-3p promotes prostate cancer stem cell expansion by targeting SFRP1 and
      GSK3beta.
AB  - Cancer stem cells promote tumor progression, drug-resistance, and relapse, and
      many microRNAs (miRNAs) play critical roles in the expansion of cancer stem
      cells. In the present study, we investigated the role of miR-1301-3p in the
      expansion of prostate cancer stem cells; miR-1301-3p was significantly
      upregulated in prostate cancer cells and tissues compared with normal prostate
      cells and tissues. Sphere formation and side population assays suggested that miR
      1301-3p promoted the expansion of prostate cancer stem cells, and increased the
      expression of prostate cancer stem cell-associated genes, such as OCT4, SOX2,
      NANOG, CD44, KLF4, c-MYC, and MMP2. MiR-1301-3p targeted Wnt pathway inhibitors,
      GSK3beta and SFRP1, and inhibited their expression by directly binding to their
      3' untranslated regions. TOP/FOP luciferase assays suggested that miR-1301-3p
      activated the Wnt pathway, which was confirmed by increased beta-catenin
      expression in the nucleus. Furthermore, the miR-1301-3p level correlated
      negatively with GSK3beta and SFRP1 in prostate cancer tissues. In summary, we
      found that miR-1301-3p promoted the expansion of prostate cancer stem cells by
      inhibiting GSK3beta and SFRP1, and activating the Wnt pathway.

PMID- 29358130
TI  - Ononitol monohydrate enhances PRDM16 & UCP-1 expression, mitochondrial biogenesis
      and insulin sensitivity via STAT6 and LTB4R in maturing adipocytes.
AB  - Ononitol monohydrate (OMH), a glycoside was originally isolated from Cassia tora
      (Linn.). Glycosides regulate lipid metabolism but scientific validation desired.
      Hence, we aimed to evaluate the effect of OMH on enhancing mitochondrial
      potential, mitochondrial biogenesis, upregulate the expression of brown
      adipogenesis specific genes in maturing adipocytes. In addition, we observed the
      inter-relation between adipocyte and T-lymphocyte; whether, OMH treated adipocyte
      condition medium stimulate T-cell chemokine linked with insulin resistance. In a
      dose dependent manner OMH treated to preadipocyte significantly inhibited
      maturation and enhanced mitochondrial biogenesis, it was confirmed by Oil red 'O
      and Nile red stain without inducing cytotoxicity. The mRNA levels of adipocyte
      browning related genes such as, PR domain containing 16 (PRDM16), peroxisome
      proliferator activated receptor gamma coactivator 1 alpha (PPARgammaC1alpha) and
      uncoupling protein-1 (UCP-1) have been significantly upregulated. In addition,
      adipogenic transcription factors [such as proliferator activated receptor gamma
      (PPARgamma), CCAAT/enhancer binding protein (C/EBPalpha) and sterol regulatory
      element binding protein-1c (SREBP-1c)] and adipogenic genes were significantly
      down-regulated by treatment with OMH when compared to control cells. Protein
      expression levels of adiponectin have been increased; leptin, C/EBPalpha and
      leukotriene B4 receptor (LTB4R) were down regulated by OMH in mature adipocytes.
      In addition, adipocyte condition medium and OMH treated T-lymphocyte,
      significantly increased insulin signaling pathway related mRNAs, such as
      interlukin-4 (IL-4), signal transducer and activator of transcription 6 (STAT6)
      and decreased leukotriene B4 (LTB4). The present findings suggest that OMH
      increased browning factors in differentiating and maturing preadipocyte also
      decreased adipose tissue inflammation as well as the enhanced insulin signaling.

PMID- 29358131
TI  - Bovine meat versus pork in Toxoplasma gondii transmission in Italy: A
      quantitative risk assessment model.
AB  - Toxoplasma gondii is a widespread zoonotic parasite with a high seroprevalence in
      the human population and the ability to infect almost all warm blooded animals.
      Humans can acquire toxoplasmosis from different transmission routes and food
      plays a critical role. Within the food category, meat is of utmost importance, as
      it may contain bradyzoites inside tissue cysts, which can potentially cause
      infection after ingestion if parasites are not inactivated through freezing or
      cooking before consumption. In Italy, the most commonly consumed meat-producing
      animal species are bovines and pigs. However, T. gondii prevalence and
      consumption habits for meat of these animal species are very different. There is
      debate within the scientific community concerning which of these animal species
      is the main source of meat-derived human toxoplasmosis. The aim of this work was
      to build a quantitative risk assessment model to estimate the yearly probability
      of acquiring toxoplasmosis infection due to consumption of bovine meat and pork
      (excluding cured products) in Italy, taking into account the different eating
      habits. The model was fitted with data obtained from the literature regarding:
      bradyzoite concentrations, portion size, dose-response relation, prevalence of T.
      gondii in bovines and swine, meat consumption and meat preparation habits.
      Alternative handling scenarios were considered. The model estimated the risk per
      year of acquiring T. gondii infection in Italy from bovine and swine meat to be
      0.034% and 0.019%, respectively. Results suggest that, due to existing eating
      habits, bovine meat can be a not negligible source of toxoplasmosis in Italy.

PMID- 29358132
TI  - Microbial inactivation and MLF performances of Tempranillo Rioja wines treated
      with PEF after alcoholic fermentation.
AB  - This study was performed with the aim of reducing the microbial communities of
      wines after alcoholic fermentation to improve the establishment of commercial
      Oenococcus oeni inoculum for developing the malolactic fermentation. Microbial
      community reduction was accomplished by applying Pulsed Electric Field (PEF)
      technology to four different wines. Overall, significant reductions in yeast
      population were observed. To a lesser extent, lactic acid bacteria were reduced
      while acetic acid bacteria were completely eliminated after the PEF treatment. In
      three out of the four tested wines, a decrease in the competitive pressure
      between microorganisms due to the detected reduction led to a general but slight
      shortening of the malolactic fermentation duration. In the wine with the most
      adverse conditions to commercial starter establishment, the shortest malolactic
      fermentation was reached after PEF treatment. Finally, the sensorial quality of
      three out of the four treated wines was considered better after the PEF
      treatment. Therefore, PEF technology meant an important tool for improving the
      malolactic fermentation performance.

PMID- 29358134
TI  - Isolation and characterization of microcrystalline cellulose from pomelo peel.
AB  - In this study, cellulose from pomelo peel (PP-C) was isolated using alkaline
      hydrogen peroxide liquor extraction, and PP-C was further hydrolyzed by
      hydrochloric acid to yield microcrystalline cellulose (PP-MCC). Several
      analytical methods were used to determine the structural characteristics,
      crystalline behavior, morphological properties, thermal properties, and water/oil
      binding capacity of PP-C and PP-MCC. Fourier-transform infrared spectra and
      morphological analysis showed that the alkaline hydrogen peroxide treatment and
      acid hydrolysis successfully removed hemicellulose and lignin from pomelo peel
      fibers. Both PP-C and PP-MCC had only a cellulose I polymorph structure, and the
      crystallinity index of PP-MCC increased compared with that of PP-C. The
      degradation temperatures of PP-C and PP-MCC were approximately 257  degrees C and
      280  degrees C, respectively. The water/oil binding capacity of PP-MCC was
      significantly higher than that of the commercial MCC. Our results thus suggested
      that PP-MCC might be suitable for use as a food stabilizer and pharmaceutical
      additive.

PMID- 29358133
TI  - Third molar agenesis as a potential marker for craniofacial deformities.
AB  - : The identification of clinical patterns of tooth agenesis in individuals born
      with craniofacial deformities may be a useful tool for risk determination of
      these defects. We hypothesize that specific craniofacial deformities are
      associated with third molar agenesis. OBJECTIVE: The aim of this study was to
      identify if third molar agenesis could have a relation with other craniofacial
      structure alterations, such as cleft lip and palate, skeletal malocclusion, or
      specific growth patterns in humans. DESIGN: Data were obtained from 550
      individuals ascertained as part of studies aiming to identify genetic
      contributions to oral clefts. 831 dental records of patients aged over eight
      years seeking orthodontic treatment were also included. SN-GoGn angle were used
      to classify the growth pattern (hypo-divergent, normal and hyper-divergent), and
      the ANB angle was used to verify the skeletal malocclusion pattern (Class I, II
      and III). Panoramic radiographs were used to determine third molar agenesis.
      RESULTS: A high frequency of third molar agenesis among individuals born with
      cleft lip with or without cleft palate (55%), as well as among their relatives
      (93.5%) was found. Third molar agenesis was not associated to skeletal
      malocclusion or growth pattern. CONCLUSION: It appears that third molar agenesis
      is associated with the disturbances that lead to cleft lip and palate.

PMID- 29358135
TI  - Effects of revegetation and precipitation gradient on soil carbon and nitrogen
      variations in deep profiles on the Loess Plateau of China.
AB  - Precipitation is one of the most important factors affecting the variations in
      soil carbon (C) and nitrogen (N) following revegetation. However, the effects of
      revegetation and precipitation gradients on soil organic carbon (SOC), total
      nitrogen (TN) and C-N interactions in deep profiles over large scales are poorly
      understood. This study measured the SOC and TN stocks to depth of 300 cm in three
      revegetation types (grassland, shrubland and forestland) and paired cropland
      stands at seven sites along a precipitation gradient with mean annual
      precipitation (MAP) from 280 to 540 mm yr-1 in the Loess Plateau of China. The
      results showed that the SOC and TN stocks in the 0-300 cm profile increased along
      the precipitation gradient. Revegetation did not always result in accumulation of
      SOC and TN stocks, which depended on the precipitation condition and varied among
      different vegetation types. Grassland restoration resulted in more SOC and TN
      accumulation than shrubland and forestland in areas with MAP < 510 mm, whereas
      there were losses in SOC and TN following grass plantation in sites with MAP >
      510 mm. The changes in SOC and TN stocks following revegetation (?SOC and ?TN)
      were significantly correlated with MAP in only the 0-20 cm layer, whereas the
      changes in the C/N ratio of each depth were significantly and negatively
      correlated with MAP. The correlations between ?SOC and ?TN were stronger in the 0
      60 cm layer than that in the 60-300 cm layer, and an accumulation of 1 g TN was
      associated with approximately 7.9 g increase of SOC in the 0-300 cm profile
      following revegetation. This study indicated that the changes in soil C and N
      stocks following revegetation had different patterns along precipitation gradient
      and among depths, and grassland restoration and N fertilizer input benefitted
      soil C and N sequestration in drier areas.

PMID- 29358136
TI  - Reduced phosphorus retention by anoxic bottom sediments after the remediation of
      an industrial acidified lake area: Indications from P, Al, and Fe sediment
      fractions.
AB  - Formerly acidified lakes and watersheds can become more productive when
      recovering from acidity, especially when exposed to anthropogenic disturbance and
      increased nutrient loading. Occasional toxic cyanobacterial blooms and other
      signs of eutrophication have been observed for a decade in lakes located in the
      Sudbury, Ontario, mining area that was severely affected by acid deposition
      before the start of smelter emission reductions in the 1970s. Oligotrophic Long
      Lake and its upstream lakes have been exposed to waste water input and
      development impacts from the City of Greater Sudbury and likely have a legacy of
      nutrient enrichment in their sediment. Based on observations from other published
      studies, we hypothesized that P, which was previously adsorbed by metals
      liberated during acidification caused by the mining activities, is now being
      released from the sediment as internal P loading contributing to increased
      cyanobacteria biomass. Support for this hypothesis includes (1) lake observations
      of oxygen depletion and hypolimnetic anoxia and slightly elevated hypolimnetic
      total P concentration and (2) P, Al, and Fe fractionation of two sediment layers
      (0-5, 5-10 cm), showing elevated concentrations of TP and iron releasable P (BD
      fraction), decreased concentrations in fractions associated with Al, and fraction
      ratios indicating decreased sediment adsorption capacity. The comparison with two
      moderately enriched lakes within 200 km distance, but never directly affected by
      mining operations, supports the increasing similarity of Long Lake surficial
      sediment adsorption capacity with that of unaffected lakes. There is cause for
      concern that increased eutrophication including the proliferation of
      cyanobacteria of formerly acidic lakes is wide-spread and occurs wherever
      recovery coincides with anthropogenic disturbances and physical changes related
      to climate change.

PMID- 29358137
TI  - Trentepohlia algae biofilms as bioindicator of atmospheric metal pollution.
AB  - In this work, a reddish biocolonization composed mainly by Trentepohlia algae
      affecting a synthetic building material from a modern building from the 90s
      located in the Bizkaia Science and Technology Park (Zamudio, North of Spain) was
      characterized and its ability to accumulate metals coming from the surrounding
      atmosphere was evaluated. To asses if these biofilms can act as bioindicators of
      the surrounding metal pollution, a fast non-invasive in situ methodology based on
      the use of hand-held energy dispersive X-ray fluorescence (HH-ED-XRF) was used.
      In order to corroborate the in situ obtained conclusions, some fragments from the
      affected material were taken to analyze the metal distribution by means of micro
      energy dispersive X-ray fluorescence spectroscopy (MU-ED-XRF) and to confirm the
      presence of metal particles deposited on it using Scanning Electron Microscopy
      coupled to an Energy Dispersive Spectrometer (SEM-EDS). In order to confirm if
      Trentepohlia algae biofilms growing on the surface of building materials could be
      a fast way to in situ provide information about the surrounding metal pollution,
      a second Trentepohlia algae biofilm growing on a different kind of material
      (sandstone) was analyzed from an older historical building, La Galea Fortress
      (Getxo, North of Spain).

PMID- 29358138
TI  - Synergistic removal effect of P in sediment of all fractions by combining the
      modified bentonite granules and submerged macrophyte.
AB  - The removal efficiency of sediment phosphorus (P) with the in-situ synergistic
      effect of modified bentonite granules (MBG) and Vallisneria spiralis (V.
      spiralis) in West Lake, Hangzhou, China was investigated for the first time in
      the study. CMBG-Na10-450 (nitrification (10% Na2CO3)-calcination (450  degrees C)
      combined modification) was prepared and characterized, and the removal effects of
      sediment P of all fractions with CMBG-Na10-450 and V. spiralis in combination and
      separately were evaluated in batch experiments. Results showed that CMBG-Na10-450
      could promote the growth of V. spiralis, and the residual P of the sediment not
      adsorbed on CMBG-Na10-450 was changed through root oxygenation and nutrition
      allocation, and then enhanced the extra P adsorption on CMBG-Na10-450. The
      combination of MBG and V. spiralis exhibited a synergistic removal effect higher
      than the summation of MBG and V. spiralis applied separately. The results of
      microcosm experiments showed that the combination of CMBG-Na10-450 and V.
      spiralis enhanced the function of P metabolism by increasing the special genus
      that belongs to the family Erysipelotrichaceae.

PMID- 29358139
TI  - Variable effects of biochar application to soils on nitrification-mediated N2O
      emissions.
AB  - Although a meta-analysis on biochar's effects on N2O emission reported an overall
      reduction in N2O emission by adding biochar to the soils, there are still
      variations in the changes in N2O emission, especially from field results. The
      objectives of this study are 1) to compare the effects of biochar addition on N2O
      emission between three agricultural upland field experiments, where soil water
      status was dry favoring nitrification and 2) to identify main factors explaining
      biochar's variable effects on N2O emission. Three field experiments were
      conducted: Exp A in the cultivated grassland treated with rice husk biochar at 2
      ton ha-1 + urea (CHAR) and with urea only (CON); Exp B in the cabbage field with
      CHAR and CON treatments; and Exp C in the pepper field with CHAR, CON, and CHAR +
      DCD (dicyandiamide, nitrification inhibitor) treatments. In Exp A and C,
      cumulative N2O emissions significantly increased by 82.5% and 55.8% in the CHAR
      than CON treatments, respectively, while in Exp B, there was no difference in
      cumulative N2O emission between the CHAR and CON. Based on results from using
      nitrification inhibitor and soil % water filled pore space (WFPS), we assumed
      that the main N2O production mechanism was nitrification. Our results suggest
      that soil water status right after urea application is the primary determinant of
      different effects of biochar on N2O emission in addition to soil C status and
      biochar's adsorption. Principal component analysis using the 25 compiled data
      also supported our results. This study identified the specific field conditions
      under which biochar could have stimulating effects on N2O emission. Mitigation
      potential of biochar application should be reconsidered if biochar and urea were
      amended to dry soils with low C contents.

PMID- 29358140
TI  - Enhanced removal of iodide ions by nano Cu2O/Cu modified activated carbon from
      simulated wastewater with improved countercurrent two-stage adsorption.
AB  - A newly developed adsorbent nano Cu2O/Cu-modified activated carbon composite
      (nano Cu2O/Cu-C) was used to remove radioactive iodide ions (I-) from simulated
      wastewater. The emphasis of this research is to improve adsorption performance
      and obtain higher I- removal efficiency compared with the single-stage
      adsorption. To fully develop the amount of adsorption by nano Cu2O/Cu-C, and to
      increase the decontamination factor (DF) of I-, an improved countercurrent two
      stage adsorption (ICTA) process was introduced. In the ICTA process, measures
      dealing with desorption of loaded adsorbent in the stage-two adsorption were
      taken and more extensive application of countercurrent two-stage adsorption (CTA)
      process could be made after the improvement to ICTA process in this study.
      Furthermore, in order to analyze the process and determine the I- concentration
      in the effluent, a calculation method was devised based on the Langmuir isotherm
      equations and adsorption accumulation principle. The mean DFs were 177, 166, and
      89.7, respectively, when the initial I- concentrations were 5.00, 10.0, and 20.0
      mg/L; and the adsorbent dosage was 1.25 g/L. These results were approximately
      8.76, 8.97, and 6.79 times higher, respectively, than with conventional single
      stage adsorption. The experimental values of the I- concentration were higher
      than the calculated ones, which could be ascribed to desorption of the residual
      loaded adsorbent and formation of CuI in the adsorption at stage 1. Formation of
      CuI in the adsorption at stage 1 was considered to be the predominant reason.

PMID- 29358141
TI  - Arsenic speciation in wild marine organisms and a health risk assessment in a
      subtropical bay of China.
AB  - The total arsenic (As) and As species were analyzed in 19 species of wild marine
      organisms collected from 12 locations in Daya Bay, China; additionally, both the
      levels of As in the seawater and sediments and the salinity were investigated.
      The greatest level of As was found in crabs (13.4-35.1 MUg/g), followed by
      shrimps (8.52-27.6 MUg/g), benthic fish (3.45-28.6 MUg/g), and pelagic fish (1.22
      5.23 MUg/g). There were significantly positive correlations between the As
      concentrations in the benthic fish Callionymus richardsonii/shrimp Metapenaeopsis
      palmensis and those in sediments, indicating that As levels in them were highly
      dependent on those in the sediments. Arsenobetaine (AsB) (87.3-99.8%) was the
      most dominant form of As found in all marine organisms. In benthic fish and
      shrimp, the bioaccumulation of As, especially AsB, was positively correlated with
      the salinity of the seawater, indicating that the salinity could control the
      transfer of As. The calculated hazard quotients (HQs) of the inorganic As in the
      marine organisms were all <1; thus, there was no apparent health hazard through
      the consumption of wild marine organisms.

PMID- 29358142
TI  - Distribution of Escherichia coli, coliphages and enteric viruses in water,
      epilithic biofilms and sediments of an urban river in Germany.
AB  - Fecal contamination of surface water is commonly evaluated by quantification of
      bacterial or viral indicators such as Escherichia coli and coliphages, or by
      direct testing for pathogens such as enteric viruses. Retention of fecally
      derived organisms in biofilms and sediments is less frequently considered. In
      this study, we assessed the distribution of E. coli, somatic coliphages, and
      enteric viruses including human adenovirus (HAdV), enterovirus (EV), norovirus
      genogroup GII (NoV GII) and group A rotavirus (RoV) in an urban river environment
      in Germany. 24 samples each of water, epilithic biofilms and sediments were
      examined. E. coli and somatic coliphages were prevalent not only in the flowing
      water, but also in epilithic biofilms and sediments, where they were accumulated
      compared to the overlying water. During enhanced rainfall, E. coli and coliphage
      concentrations increased by approximately 2.5 and 1 log unit, respectively, in
      the flowing water, whereas concentrations did not change significantly in
      epilithic biofilms and sediments. The occurrence of human enteric viruses
      detected by qPCR was higher in water than in biofilms and sediments. 87.5% of all
      water samples were positive for HAdV. Enteric viruses found less frequently were
      EV, RoV and NoV GII in 20.8%, 16.7% and 8.3% of the water samples, respectively.
      In epilithic biofilms and sediments, HAdV was found in 54.2% and 50.0% of the
      samples, respectively, and EV was found in 4.2% of both biofilm and sediment
      samples. RoV and NoV GII were not detected in any of the biofilms and sediments.
      Overall, the prevalence of enteric viruses was in the order of HAdV > EV > RoV >=
      NoV GII. In conclusion, epilithic biofilms and sediments can be reservoirs for
      fecal indicators and enteric viruses and thus should be taken into consideration
      when assessing microbial pollution of surface water environments.

PMID- 29358143
TI  - Inventories and reduction scenarios of urban waste-related greenhouse gas
      emissions for management potential.
AB  - Waste-related greenhouse gas (GHG) emissions have been recognized as one of the
      prominent contributors to global warming. Current urban waste regulations,
      however, face increasing challenges from stakeholders' trade-offs and hierarchic
      management. A combined method, i.e., life cycle inventories and scenario
      analysis, was employed to investigate waste-related GHG emissions during 1995
      2015 and to project future scenarios of waste-driven carbon emissions by 2050 in
      a pilot low carbon city, Xiamen, China. The process-based carbon analysis of
      waste generation (prevention and separation), transportation (collection and
      transfer) and disposal (treatment and recycling) shows that the main contributors
      of carbon emissions are associated with waste disposal processes, solid waste,
      the municipal sector and Xiamen Mainland. Significant spatial differences of
      waste-related CO2e emissions were observed between Xiamen Island and Xiamen
      Mainland using the carbon intensity and density indexes. An uptrend of waste
      related CO2e emissions from 2015 to 2050 is identified in the business as usual,
      waste disposal optimization, waste reduction and the integrated scenario, with
      mean annual growth rates of 8.86%, 8.42%, 6.90% and 6.61%, respectively. The
      scenario and sensitivity analysis imply that effective waste-related carbon
      reduction requires trade-offs among alternative strategies, actions and
      stakeholders in a feasible plan, and emphasize a priority of waste prevention and
      collection in Xiamen. Our results could benefit to the future modeling of urban
      multiple wastes and life-cycle carbon control in similar cities within and beyond
      China.

PMID- 29358144
TI  - Bioaccumulation and oxidative stress caused by pesticides in Cyprinus carpio
      reared in a rice-fish system.
AB  - Nowadays, many irrigated rice producers have adopted the rice-fish farming
      systems, in which fish are reared in the same environment as rice is grown. These
      animals can biologically control many pests that disturb the crop, as well as
      increase the income of producers when they are reared in the same area as rice.
      However, a large variety of pesticides is often used for pest control in
      conventional irrigated rice crops, and fish are exposed to different pesticide
      concentrations and active ingredients. Thus, the aim of the current study is to
      assess the potential risks of these pesticides to freshwater fish (Cyprinus
      carpio) cultured in integrated rice-fish farming systems. We assessed five
      pesticides widely used in rice culture. This is the first report on the
      bioaccumulation of the insecticides lambda-cyhalothrin + thiamethoxam and
      clorantraniliprole and of the fungicide tebuconazole + trifloxystrobin associated
      with oxidative stress and with enzymatic and non-enzymatic parameters in edible
      fish samples reared in integrated in rice-fish farming systems. After 100 days of
      exposure, lambda-cyhalothrin and tebuconazole bioaccumulated in carp muscles.
      Acethylcholinesterase activity in the brain was lower in the experimental group
      than in the control group. Overall, the biochemical analyses showed increased
      responses in the experimental groups in comparison to the controls. Lipid
      peroxidation levels increased in the liver, gills and muscles. Protein oxidation
      increased in the liver and muscles. Catalase activity increased in the liver, and
      glutathione S-transferase increased in the liver, gills and muscles. Results
      demonstrate that these pesticides have severe adverse consequences in fish and
      indicate their potential risk to human health due to their bioaccumulation in
      farmed fish.

PMID- 29358145
TI  - Integrating uncertainties to the combined environmental and economic assessment
      of algal biorefineries: A Monte Carlo approach.
AB  - The economic and environmental performance of microalgal processes has been
      widely analyzed in recent years. However, few studies propose an integrated
      process-based approach to evaluate economic and environmental indicators
      simultaneously. Biodiesel is usually the single product and the effect of
      environmental benefits of co-products obtained in the process is rarely
      discussed. In addition, there is wide variation of the results due to inherent
      variability of some parameters as well as different assumptions in the models and
      limited knowledge about the processes. In this study, two standardized models
      were combined to provide an integrated simulation tool allowing the simultaneous
      estimation of economic and environmental indicators from a unique set of input
      parameters. First, a harmonized scenario was assessed to validate the joint
      environmental and techno-economic model. The findings were consistent with
      previous assessments. In a second stage, a Monte Carlo simulation was applied to
      evaluate the influence of variable and uncertain parameters in the model output,
      as well as the correlations between the different outputs. The simulation showed
      a high probability of achieving favorable environmental performance for the
      evaluated categories and a minimum selling price ranging from $11gal-1 to $106gal
      1. Greenhouse gas emissions and minimum selling price were found to have the
      strongest positive linear relationship, whereas eutrophication showed weak
      correlations with the other indicators (namely greenhouse gas emissions,
      cumulative energy demand and minimum selling price). Process parameters
      (especially biomass productivity and lipid content) were the main source of
      variation, whereas uncertainties linked to the characterization methods and
      economic parameters had limited effect on the results.

PMID- 29358146
TI  - Soybean supplementation increases the resilience of microbial and nematode
      communities in soil to extreme rainfall in an agroforestry system.
AB  - A current challenge for ecological research in agriculture is to identify ways in
      which to improve the resilience of the soil food web to extreme climate events,
      such as severe rainfall. Plant species composition influence soil biota
      communities differently, which might affect the recovery of soil food web after
      extreme rainfall. We compared the effects of rainfall stress up on the soil
      microbial food web in three planting systems: a monoculture of the focal species
      Zanthoxylum bungeanum and mixed cultures of Z. bungeanum and Medicago sativa or
      Z. bungeanum and Glycine max. We tested the effect of the presence of a legume on
      the recovery of trophic interactions between microorganisms and nematodes after
      extreme rainfall. Our results indicated that all chemical properties of the soil
      recovered to control levels (normal rainfall) in the three planting systems 45
      days after exposure to extreme rain. However, on day 45, the bulk microbial
      community differed from controls in the monoculture treatment, but not in the two
      mixed planting treatments. The nematode community did not fully recover in the
      monoculture or Z. bungeanum and M. sativa treatments, while nematode populations
      in the combined Z. bungeanum and G. max treatment were indistinguishable from
      controls. G. max performed better than M. sativa in terms of increasing the
      resilience of microbial and nematode communities to extreme rainfall. Soil
      microbial biomass and nematode density were positively correlated with the
      available carbon and nitrogen content in soil, demonstrating a link between soil
      health and biological properties. This study demonstrated that certain leguminous
      plants can stabilize the soil food web via interactions with soil biota
      communities after extreme rainfall.

PMID- 29358147
TI  - Synthesis and biological evaluation of aurora kinases inhibitors based on N
      trisubstituted pyrimidine scaffold.
AB  - The inhibition of the members of aurora kinase family using ATP-competitive small
      molecules is an effective method for anticancer therapeutics. Based on our
      previous work, we synthesized 12 new N-trisubstituted pyrimidine derivatives and
      evaluated their biological activities and stabilities. Among them, compound 11j
      showed the best inhibition against aurora A kinase (IC50 = 7.1 nM), human
      leukemia cell line U937 (IC50 = 12.2 nM) and the growth of U937 xenograft tumors
      in vivo. By the flow cytometry and immunofluorescence analysis of U937, we found
      that compound 11j can induced polyploidy formation including (4N, 8N and 16N) and
      induce defects in both chromosome alignment and spindle formation. Furthermore,
      compound 11j exhibited good chemical, physical, and thermal stabilities. All
      these results suggested that 11j is a promising lead compound for further
      development of anticancer drugs.

PMID- 29358148
TI  - First detection and genomics analysis of KPC-2-producing Citrobacter isolates
      from river sediments.
AB  - The wide spread of carbapenemase-producing Enterobacteriaceae (CPE) in the
      environment is an emerging environmental issue with potentially-serious public
      health implications. However, carbapenemase-producing Citrobacter from
      environment has rarely been investigated. Here we report the isolation and
      comparative genomics of carbapenemase-producing Citrobacter isolates from river
      sediment in China. Potential CPE was isolated by selective MacConkey agar plates
      containing 2 mg/L meropenem. The presence of carbapenemase genes was detected by
      PCR and sequencing. The clonal relatedness of Klebsiella pneumoniae carbapenemase
      (KPC-2)-producing Citrobacter isolates was assessed by pulsed-field gel
      electrophoresis (PFGE) and multilocus sequence typing. Plasmid analysis of KPC-2
      producing Citrobacter isolates was performed by S1-PFGE, Southern blotting, and
      whole genome sequencing. A total of four KPC-2-producing Citrobacter and three
      Aeromonas isolates were recovered from 54 sediment cultures of Shifeng River.
      Notably, all KPC-producing isolates were isolated from sampling sites near a
      waste water treatment plant. Antimicrobial susceptibility testing showed that
      three of the four sequenced isolates (C1710, C191, and C196) resistant to
      multiple antibiotics. Genotyping and pan-genome analyses revealed that the C191
      and C196 C. freundii isolates exhibited a high level of genetic similarity.
      Plasmid analysis confirmed that the blaKPC-2 gene is located on either IncF or
      IncN3 plasmids in all isolates. The blaKPC-2 gene of C1710, C181 and C191 was
      successfully transferred with E. coli EC600 as the recipient strain. In silico
      analysis further suggested that pKPC-191 is a novel IncF plasmid, with 99%
      identity to two previously described IncFII plasmids at 71% coverage. We report
      here the presence of diverse conjugative blaKPC-2 plasmids from environmental
      Citrobacter isolates, which poses the possible dissemination of antimicrobial
      resistance into clinical isolates. To our knowledge, this is the first study to
      culture and characterize KPC-2-producing Citrobacter isolates from river
      sediments in China.

PMID- 29358149
TI  - Decline in atmospheric sulphur deposition and changes in climate are the major
      drivers of long-term change in grassland plant communities in Scotland.
AB  - The predicted long lag time between a decrease in atmospheric deposition and a
      measured response in vegetation has generally excluded the investigation of
      vegetation recovery from the impacts of atmospheric deposition. However, policy
      makers require such evidence to assess whether policy decisions to reduce
      emissions will have a positive impact on habitats. Here we have shown that 40
      years after the peak of SOx emissions, decreases in SOx are related to
      significant changes in species richness and cover in Scottish Calcareous,
      Mestrophic, Nardus and Wet grasslands. Using a survey of vegetation plots across
      Scotland, first carried out between 1958 and 1987 and resurveyed between 2012 and
      2014, we test whether temporal changes in species richness and cover of
      bryophytes, Cyperaceae, forbs, Poaceae, and Juncaceae can be explained by changes
      in sulphur and nitrogen deposition, climate and/or grazing intensity, and whether
      these patterns differ between six grassland habitats: Acid, Calcareous, Lolium,
      Nardus, Mesotrophic and Wet grasslands. The results indicate that Calcareous,
      Mesotrophic, Nardus and Wet grasslands in Scotland are starting to recover from
      the UK peak of SOx deposition in the 1970's. A decline in the cover of grasses,
      an increase in cover of bryophytes and forbs and the development of a more
      diverse sward (a reversal of the impacts of increased SOx) was related to
      decreased SOx deposition. However there was no evidence of a recovery from SOx
      deposition in the Acid or Lolium grasslands. Despite a decline in NOx deposition
      between the two surveys we found no evidence of a reversal of the impacts of
      increased N deposition. The climate also changed significantly between the two
      surveys, becoming warmer and wetter. This change in climate was related to
      significant changes in both the cover and species richness of bryophytes,
      Cyperaceae, forbs, Poaceae and Juncaceae but the changes differed between
      habitats.

PMID- 29358150
TI  - Micromechanisms of fatigue crack growth in polycarbonate polyurethane: Time
      dependent and hydration effects.
AB  - Polycarbonate polyurethane has cartilage-like, hygroscopic, and elastomeric
      properties that make it an attractive material for orthopedic joint replacement
      application. However, little data exists on the cyclic loading and fracture
      behavior of polycarbonate polyurethane. This study investigates the mechanisms of
      fatigue crack growth in polycarbonate polyurethane with respect to time dependent
      effects and conditioning. We studied two commercially available polycarbonate
      polyurethanes, Bionate(r) 75D and 80A. Tension testing was performed on specimens
      at variable time points after being removed from hydration and variable strain
      rates. Fatigue crack propagation characterized three aspects of loading. Study 1
      investigated the impact of continuous loading (24h/day) versus intermittent
      loading (8-10h/day) allowing for relaxation overnight. Study 2 evaluated the
      effect of frequency and study 3 examined the impact of hydration on the fatigue
      crack propagation in polycarbonate polyurethane. Samples loaded intermittently
      failed instantaneously and prematurely upon reloading while samples loaded
      continuously sustained longer stable cracks. Crack growth for samples tested at 2
      and 5Hz was largely planar with little crack deflection. However, samples tested
      at 10Hz showed high degrees of crack tip deflection and multiple crack fronts.
      Crack growth in hydrated samples proceeded with much greater ductile crack mouth
      opening displacement than dry samples. An understanding of the failure mechanisms
      of this polymer is important to assess the long-term structural integrity of this
      material for use in load-bearing orthopedic implant applications.

PMID- 29358151
TI  - Prediction of circumferential compliance and burst strength of polymeric vascular
      grafts.
AB  - The circumferential compliance and burst strength of vascular grafts are
      predicted through the conically modified von Mises and elasticity theories,
      providing an analytical closed form solution for both parameters. Besides the
      graft's radii, the model for circumferential compliance depends solely on the
      elastic modulus and Poisson's ratio of the polymer material, and its accuracy was
      verified by finite element analysis and measurements. The analytical expression
      of the burst strength requires accurate determination of the material's tensile
      and compressive yield stress, which were carefully obtained by using digital
      image correlation measurements in uniaxial tensile and compressive tests of the
      constitutive material. The average measured circumferential compliance and burst
      strength of an 8mm graft made of a commonly used biomaterial, Tecoflex(r) SG-80A,
      are 1.05%/100mmHg-1 and 34.1psi (1763mmHg) and the proposed analytical
      predictions fall within the experimental scattering. Thus, it is shown that the
      circumferential compliance and burst strength of vascular grafts can be
      analytically predicted by knowing the elastic and yield material properties
      accurately, without needing to actually test the graft under radial pressure.
      This is a major advantage which can aid in the design and tailoring of vascular
      grafts.

PMID- 29358152
TI  - How proteolytic inhibitors interact with dentin on glass-fiber post luting over 6
      months.
AB  - OBJECTIVES: Enzyme inhibitors minimize the degradation of unprotected collagen of
      dentin promoted by matrix metalloproteinases (MMPs) and cysteine cathepsins
      (CCs). As the evidence of their effect on the root canal is limited, this study
      aimed to evaluate the role of EDTA, chlorhexidine and E-64 as antiproteolytic
      agents on the bond strength (BS) of glass-fiber posts in root canals. MATERIALS
      AND METHODS: Ninety-six bovine roots were distributed in groups for each time
      point (n = 8). Adper Scotchbond Multipurpose (MP)/ RelyX ARC system was used to
      lute the post according to the treatment: negative control (NC)- water, EDTA- 17%
      ethylenediaminetetraacetic acid, CHX- 2% digluconate chlorhexidine, E-64-5- 5MUM
      E-64, E-64-10- 10MUM E-64 and positive control (PC)- MP associated with
      activator/ catalyst. Then, slices were subjected to push-out test (0.5mm/min)
      after 24h/6 mons. Data were analyzed by three-way ANOVA/Tukey tests. Failure
      modes were analyzed (40*). RESULTS: The factors treatment, time, root canal third
      and the interaction between treatment and time were statistically significant. At
      24h, no negative interactions were observed among the root dentin, bonding system
      and post. At 6 mons, CHX improved the BS for middle and apical root thirds.
      CONCLUSIONS: CHX was able to promote beneficial BS after 6 mons, which was not
      noted for any other tested enzyme inhibitors.

PMID- 29358153
TI  - Ferulic acid derivatives from Ligusticum chuanxiong.
AB  - Four new ferulic acid derivatives ligusticumacid A-C (1-3) and ligusticumaldehyde
      A (4), one new dimer ligusticumacid D (5), and two novel 8-8' lignans
      ligusticumacid E-F (6-7) were isolated from the rhizome of Ligusticum chuanxiong
      Hort. In particular, compounds 1-2, 5 were rarely phenylpropanoid phenolic acid
      dimers through different polymerization action in natural products. Their
      structures were established using UV, IR, HRESIMS, NMR data. The absolute
      configurations of 3 was determined by quantum ECD calculation and 4, 6-7 were
      determined by the ECD exciton chirality method. In addition, all compounds were
      evaluated for their neuroprotective effects on human neuroblastoma SH-SY5Y cell
      injury induced by H2O2. Compound 2 had a moderate neuroprotective activity and 7
      had a weak neuroprotective activity on human neuroblastoma SH-SY5Y cell injury
      induced by H2O2 respectively.

PMID- 29358154
TI  - Development and single-laboratory validation of a UHPLC-MS/MS method for
      quantitation of microcystins and nodularin in natural water, cyanobacteria,
      shellfish and algal supplement tablet powders.
AB  - A simple, rapid UHPLC-MS/MS method has been developed and optimised for the
      quantitation of microcystins and nodularin in wide variety of sample matrices.
      Microcystin analogues targeted were MC-LR, MC-RR, MC-LA, MC-LY, MC-LF, LC-LW, MC
      YR, MC-WR, [Asp3] MC-LR, [Dha7] MC-LR, MC-HilR and MC-HtyR. Optimisation studies
      were conducted to develop a simple, quick and efficient extraction protocol
      without the need for complex pre-analysis concentration procedures, together with
      a rapid sub 5min chromatographic separation of toxins in shellfish and algal
      supplement tablet powders, as well as water and cyanobacterial bloom samples.
      Validation studies were undertaken on each matrix-analyte combination to the full
      method performance characteristics following international guidelines. The method
      was found to be specific and linear over the full calibration range. Method
      sensitivity in terms of limits of detection, quantitation and reporting were
      found to be significantly improved in comparison to LC-UV methods and applicable
      to the analysis of each of the four matrices. Overall, acceptable recoveries were
      determined for each of the matrices studied, with associated precision and within
      laboratory reproducibility well within expected guidance limits. Results from the
      formalised ruggedness analysis of all available cyanotoxins, showed that the
      method was robust for all parameters investigated. The results presented here
      show that the optimised LC-MS/MS method for cyanotoxins is fit for the purpose of
      detection and quantitation of a range of microcystins and nodularin in shellfish,
      algal supplement tablet powder, water and cyanobacteria. The method provides a
      valuable early warning tool for the rapid, routine extraction and analysis of
      natural waters, cyanobacterial blooms, algal powders, food supplements and
      shellfish tissues, enabling monitoring labs to supplement traditional microscopy
      techniques and report toxicity results within a short timeframe of sample
      receipt. The new method, now accredited to ISO17025 standard, is simple, quick,
      applicable to multiple matrices and is highly suitable for use as a routine, high
      throughout, fast turnaround regulatory monitoring tool.

PMID- 29358155
TI  - The infant disorganised attachment classification: "Patterning within the
      disturbance of coherence".
AB  - Since its introduction by Main and Solomon in 1990, the infant disorganised
      attachment classification has functioned as a predictor of mental health in
      developmental psychology research. It has also been used by practitioners as an
      indicator of inadequate parenting and developmental risk, at times with greater
      confidence than research would support. Although attachment disorganisation takes
      many forms, it is generally understood to reflect a child's experience of being
      repeatedly alarmed by their parent's behaviour. In this paper we analyse how the
      infant disorganised attachment classification has been stabilised and
      interpreted, reporting results from archival study, ethnographic observations at
      four training institutes for coding disorganised attachment, interviews with
      researchers, certified coders and clinicians, and focus groups with child welfare
      practitioners. Our analysis points to the role of power/knowledge disjunctures in
      hindering communication between key groups: Main and Solomon and their readers;
      the oral culture of coders and the written culture of published papers; the
      research community and practitioners. We highlight how understandings of
      disorganised attachment have been magnetised by a simplified image of a child
      fearful of his or her own parent.

PMID- 29358156
TI  - The effects of calcineurin inhibitor FK506 on actin cytoskeleton, neuronal
      survival and glial reactions after pilocarpine-induced status epilepticus in
      mice.
AB  - After status epilepticus (SE), actin cytoskeleton (F-actin) becomes progressively
      deconstructed in the hippocampus, which is consistent with the delayed pyramidal
      cell death in both time course and spatial distribution. A variety of experiments
      show that calcineurin inhibitors such as FK506 are able to inhibit the SE-induced
      actin depolymerization. However, it is still unclear what changes happen to the F
      actin in the epileptic brain after FK506 treatment. A pilocarpine model of SE in
      mice was used to examine the effects of FK506 on the F-actin in the hippocampal
      neurons. The post SE (PSE) mice with or without FK506 treatment were monitored
      consecutively for 14 days to examine the frequency and duration of spontaneous
      seizures. The effects of FK506 on the activity of cofilin and actin dynamics were
      assessed at 7 and 14 d PSE by western blots. The organization of F-actin,
      neuronal cell death, and glial reactions were investigated by phalloidin
      staining, histological and immunocytochemical staining, respectively. As compared
      to the PSE + vehicle mice, FK506 treatment significantly decreased the frequency
      and duration of spontaneous seizures. Relative to the PSE + vehicle mice, western
      blots detected a partial restoration of phosphorylated cofilin and a significant
      increase of F/G ratio in the hippocampus after FK506 treatment. In the PSE +
      vehicle mice, almost no F-actin puncta were left in the CA1 and CA3 subfields at
      7 and 14 d PSE. FK506-treated PSE mice showed a similar decrease of F-actin, but
      the extent of damage was significantly ameliorated. Consistently, the surviving
      neurons became significantly increased in number after FK506 treatment, relative
      to the PSE + vehicle groups. After FK506 treatment, microglial reaction was
      partially inhibited, but the expression of GFAP was not significantly changed,
      compared to the PSE + vehicle mice. The results suggest that post-epileptic
      treatment with FK506 ameliorated, but could not stop the deconstruction of F
      actin or the delayed neuronal loss in the PSE mice.

PMID- 29358157
TI  - Alterations of theta oscillation in executive control in temporal lobe epilepsy
      patients.
AB  - Attention dysfunction, especially executive control has been investigated within
      many types of diseases of the central nervous system. The present study aims to
      clarify alterations of the executive control (EC) network in patients with
      temporal lobe epilepsy (TLE). Twenty patients with TLE and 20 matched healthy
      control subjects participated in the attention network test (ANT), and scalp
      electroencephalogram (EEG) recordings were set up. The ANT was used to evaluate
      attention network behavior deficits. Power spectral density (PSD), coherence and
      correlation were used to detect power and oscillation alterations of attention
      network in patients with TLE. The most significant differences in executive
      control were found between patients with TLE and healthy control subjects. Power
      spectral density in the theta band, and coherence and correlation in the theta
      band in the frontal area were decreased in patients with TLE. Our results
      indicate that patients with TLE have severe attention dysfunction, especially in
      executive control. In addition, brain theta oscillation impairment in frontal
      area might be connected with poor executive control behavior. These findings will
      provide new insight into diagnosing and treating patients with temporal lobe
      epilepsy.

PMID- 29358158
TI  - Internet-Based Cognitive Behavioral Therapy for Children and Adolescents With
      Dental Anxiety: Open Trial.
AB  - BACKGROUND: Cognitive behavioral therapy (CBT) is an evidence-based method for
      treating specific phobias, but access to treatment is difficult, especially for
      children and adolescents with dental anxiety. Psychologist-guided Internet-based
      CBT (ICBT) may be an effective way of increasing accessibility while maintaining
      treatment effects. OBJECTIVE: The aim of this study was to test the hypothesis
      that psychologist-guided ICBT improves school-aged children's and adolescents'
      ability to manage dental anxiety by (1) decreasing avoidance and affecting the
      phobia diagnosis and (2) decreasing the dental fear and increasing the target
      groups' self-efficacy. The study also aimed to examine the feasibility and
      acceptability of this novel treatment. METHODS: This was an open, uncontrolled
      trial with assessments at baseline, posttreatment, and the 1-year follow-up. The
      study enrolled and treated 18 participants. The primary outcome was level of
      avoidance behaviors, as measured by the picture-guided behavioral avoidance test
      (PG-BAT). The secondary outcome was a diagnostic evaluation with the parents
      conducted by a psychologist. The specific phobia section of the structured
      interview Kiddie-Schedule for Affective Disorders and Schizophrenia for School
      Age Children-Present and Lifetime (K-SADS-PL) was used. Other outcome measures
      included level of dental anxiety and self-efficacy. The ICBT, which employed
      exposure therapy, comprised 12 modules of texts, animations, dentistry-related
      video clips, and an exercise package (including dental instruments). Participants
      accessed the treatment through an Internet-based treatment platform and received
      Web-based guidance from a psychologist. Treatment also included training at
      dental clinics. Feasibility and acceptability were assessed by measures of
      engagement, adherence, compliance, completed measures, patient and parent
      satisfaction scale, and staff acceptability. RESULTS: The level of avoidance
      (according to the primary outcome measure PG-BAT) and dental anxiety decreased
      and self-efficacy increased significantly (P<.001), within-group effect sizes for
      both the primary outcome (Cohen d=1.5), and other outcomes were large in the
      range of 0.9 and 1.5. According to K-SADS-PL, 53% (8/15) of the participants were
      free from diagnosable dental anxiety at the 1-year follow-up. At the 1-year
      follow-up, improvements were maintained and clinically significant, with 60%
      (9/15) of participants who had been unable to manage intraoral injection of local
      anesthetics before ICBT reporting having accomplished this task at a dental
      clinic. The target group showed improvement in all the outcome measures. High
      levels of feasibility and acceptability were observed for the treatment.
      CONCLUSIONS: ICBT is a promising and feasible treatment for dental anxiety in
      children and adolescents. Integrating it into routine pediatric dental care would
      increase access to an effective psychological treatment. The results of this open
      trial must be replicated in controlled studies.

PMID- 29358159
TI  - A Natural Language Processing System That Links Medical Terms in Electronic
      Health Record Notes to Lay Definitions: System Development Using Physician
      Reviews.
AB  - BACKGROUND: Many health care systems now allow patients to access their
      electronic health record (EHR) notes online through patient portals. Medical
      jargon in EHR notes can confuse patients, which may interfere with potential
      benefits of patient access to EHR notes. OBJECTIVE: The aim of this study was to
      develop and evaluate the usability and content quality of NoteAid, a Web-based
      natural language processing system that links medical terms in EHR notes to lay
      definitions, that is, definitions easily understood by lay people. METHODS:
      NoteAid incorporates two core components: CoDeMed, a lexical resource of lay
      definitions for medical terms, and MedLink, a computational unit that links
      medical terms to lay definitions. We developed innovative computational methods,
      including an adapted distant supervision algorithm to prioritize medical terms
      important for EHR comprehension to facilitate the effort of building CoDeMed. Ten
      physician domain experts evaluated the user interface and content quality of
      NoteAid. The evaluation protocol included a cognitive walkthrough session and a
      postsession questionnaire. Physician feedback sessions were audio-recorded. We
      used standard content analysis methods to analyze qualitative data from these
      sessions. RESULTS: Physician feedback was mixed. Positive feedback on NoteAid
      included (1) Easy to use, (2) Good visual display, (3) Satisfactory system speed,
      and (4) Adequate lay definitions. Opportunities for improvement arising from
      evaluation sessions and feedback included (1) improving the display of
      definitions for partially matched terms, (2) including more medical terms in
      CoDeMed, (3) improving the handling of terms whose definitions vary depending on
      different contexts, and (4) standardizing the scope of definitions for medicines.
      On the basis of these results, we have improved NoteAid's user interface and a
      number of definitions, and added 4502 more definitions in CoDeMed. CONCLUSIONS:
      Physician evaluation yielded useful feedback for content validation and
      refinement of this innovative tool that has the potential to improve patient EHR
      comprehension and experience using patient portals. Future ongoing work will
      develop algorithms to handle ambiguous medical terms and test and evaluate
      NoteAid with patients.

PMID- 29358162
TI  - Man wins right to take assisted dying case to Court of Appeal.

PMID- 29358163
TI  - Emergency cancer diagnoses in England fall from in 24% to 20% in 10 years.

PMID- 29358161
TI  - Translation and Validation of the Nomophobia Questionnaire in the Italian
      Language: Exploratory Factor Analysis.
AB  - BACKGROUND: Nomophobia, which is a neologism derived from the combination of "no
      mobile," "phone," and "phobia" is considered to be a modern situational phobia
      and indicates a fear of feeling disconnected. OBJECTIVE: No psychometric scales
      are available in Italian for investigating such a construct. We therefore planned
      a translation and validation study of the Nomophobia Questionnaire (NMP-Q), which
      is an instrument developed by Yildirim and Correia. Subjects were recruited via
      an online survey using a snowball approach. METHODS: The NMP-Q was translated
      from English into Italian using a classical "backwards and forwards" procedure.
      In order to explore the underlying factor structure of the translated
      questionnaire, an exploratory factor analysis was carried out. A principal
      component analysis approach with varimax rotation was performed. Multivariate
      regression analyses were computed to shed light on the psychological predictors
      of nomophobia. RESULTS: A sample of 403 subjects volunteered to take part in the
      study. The average age of participants was 27.91 years (standard deviation 8.63)
      and the sample was comprised of 160 males (160/403, 39.7%) and 243 females
      (243/403, 60.3%). Forty-five subjects spent less than 1 hour on their mobile
      phone per day (45/403, 11.2%), 94 spent between 1 and 2 hours (94/403, 23.3%), 69
      spent between 2 and 3 hours (69/403, 17.1%), 58 spent between 3 and 4 hours
      (58/403, 14.4%), 48 spent between 4 and 5 hours (48/403, 11.9%), 29 spent between
      5 and 7 hours (29/403, 7.2%), 36 spent between 7 and 9 hours (36/403, 8.9%), and
      24 spent more than 10 hours (24/403, 6.0%). The eigenvalues and scree plot
      supported a 3-factorial nature of the translated questionnaire. The NMP-Q showed
      an overall Cronbach alpha coefficient of 0.95 (0.94, 0.89, and 0.88 for the three
      factors). The first factor explained up to 23.32% of the total variance, while
      the second and third factors explained up to 23.91% and 18.67% of the variance,
      respectively. The total NMP-Q score correlated with the number of hours spent on
      a mobile phone. CONCLUSIONS: The Italian version of the NMP-Q proved to be
      reliable.

PMID- 29358160
TI  - Awareness of Prevention Strategies and Willingness to Use Preexposure Prophylaxis
      in Brazilian Men Who Have Sex With Men Using Apps for Sexual Encounters: Online
      Cross-Sectional Study.
AB  - BACKGROUND: Geosocial networking (GSN) smartphone apps are becoming the main
      venue for sexual encounters among Brazilian men who have sex with men (MSM). To
      address the increased HIV incidence in this population, preexposure prophylaxis
      (PrEP) was recently implemented in the Brazilian public health system in the
      context of combined HIV prevention. OBJECTIVE: This study aimed to describe the
      characteristics of MSM using GSN apps for sexual encounters, their awareness of
      prevention strategies, and willingness to use PrEP. METHODS: This study was an
      online cross-sectional study conducted in 10 Brazilian state capitals from July 1
      to July 31, 2016. The questionnaire was programmed on SurveyGizmo and advertised
      in two GSN apps used by MSM to find sexual partners (Hornet and Grindr).
      Inclusion criteria were >18 years of age, cisgender men, with an HIV-negative
      status. Eligible individuals answered questions on: demographics; behavior; and
      knowledge, preferences, and willingness to use PrEP, nonoccupational postexposure
      prophylaxis (nPEP), HIV self-testing (HIVST), and condoms. Logistic regression
      modeling was performed to assess the factors associated with daily oral PrEP
      willingness. RESULTS: During the study period, 8885 individuals provided consent
      and started the questionnaire. Of these, 23.05% (2048/8885) were ineligible, 6837
      (6837/8885, 76.94%) initiated, and 5065 (5065/8885, 57.00%) completed the entire
      questionnaire and were included in the present analysis. Median age was 30 years
      (interquartile range: 25-36), most self-declared as MSM (4991/5065, 98.54%),
      white (3194/5065, 63.06%), middle income (2148/5065, 42.41%), and had 12 or more
      years of schooling (3106/5062, 61.36%). The majority of MSM (3363/5064, 66.41%)
      scored >10 points (high risk) on The HIV Incidence Risk for MSM Scale, but only
      21.39% (1083/5064) had a low perceived likelihood of getting HIV in the next
      year. Daily use of apps for sex was reported by 35.58% (1798/5054). Most MSM
      (4327/5065, 85.43%) reported testing for HIV at least once in their lifetime and
      9.16% (464/5065) used nPEP in the previous year. PrEP, nPEP, and HIVST awareness
      was reported by 57.89% (2932/5065), 57.39% (2907/5065), and 26.57% (1346/5065) of
      participants, respectively. Half of all respondents (2653/5065, 52.38%) were
      willing to use daily oral PrEP, and this finding was associated with higher
      numbers of male sexual partners (adjusted odds ratio [AOR] 1.26, 95% CI 1.09
      1.47), condomless receptive anal intercourse (AOR 1.27, 95% CI 1.12-1.44), sex
      with HIV-positive partner versus no HIV-positive partner (one HIV-positive
      partner: AOR 1.36, 95% CI 1.11-1.67), daily use of apps for sexual encounters
      (AOR 1.48, 95% CI 1.17-1.87), high and unknown perceived likelihood of getting
      HIV in the next year (AOR 1.72, 95% CI 1.47-2.02 and AOR 1.39, 95% CI 1.13-1.70),
      sexually transmitted infection diagnosis (AOR 1.25, 95% CI 1.03-1.51), stimulant
      use (AOR 1.24, 95% CI 1.07-1.43), PrEP awareness (AOR 1.48, 95% CI 1.30-1.70),
      and unwillingness to use condoms (AOR 1.16, 95% CI 1.00-1.33). CONCLUSIONS: Our
      results evidenced high-risk scores in the studied population, suggesting the
      importance of PrEP use. Those individuals presenting risky sexual behaviors were
      more willing to use PrEP. Nonetheless, only 58% (2932/5065) of individuals had
      heard about this prevention strategy. Efforts to increase awareness of new
      prevention strategies are needed, and mobile health tools are a promising
      strategy to reach MSM.

PMID- 29358164
TI  - Hepatic metabolomic profiling changes along with postnatal liver maturation in
      breeder roosters.
AB  - To understand the hepatic metabolic changes during postnatal liver maturation
      process in breeder roosters, we investigated the hepatic metabolites composition
      of 1-day-old, 42-day-old, and 35-week-old breeder roosters using gas
      chromatography-mass spectrometer (GC-MS). Comprehensive multivariate data
      analyses were applied to identify the distinguishing metabolites of liver. 84
      different kinds of distinguishing metabolites were identified between the livers
      of 1-day-old and 42-day-old breeder roosters, and 58 different kinds of
      distinguishing metabolites were identified between the livers from 42-day-old and
      35-week-old breeder roosters. Further pathway annotations revealed that the
      hepatic metabolism was extensively remodeled during the postnatal liver
      maturation process. The antioxidant capacity of the liver and metabolism of
      carbohydrates, proteins, amino acids, fats, cholesterols, nucleic acids, and
      vitamins were all significantly changed at different growing periods after birth.
      Specifically, we found that the hepatic amino acid metabolic function was
      continuously enhanced from 1-day-old to 35-week-old roosters. However, the
      glucose and lipid metabolic functions were weakened from 1-day-old to 42-day-old
      roosters and then elevated from 42-day-old to 35-week-old roosters. In
      conclusion, the present study revealed that the metabolomic changes are related
      to the adaption of liver functions in breeder roosters.

PMID- 29358165
TI  - Functional analysis of thyroid hormone receptor beta in Xenopus tropicalis
      founders using CRISPR-Cas.
AB  - Amphibians provide an ideal model to study the actions of thyroid hormone (TH) in
      animal development because TH signaling via two TH receptors, TRalpha and TRbeta,
      is indispensable for amphibian metamorphosis. However, specific roles for the
      TRbeta isoform in metamorphosis are poorly understood. To address this issue, we
      generated trbeta-disrupted Xenopus tropicalis tadpoles using the CRISPR-Cas
      system. We first established a highly efficient and rapid workflow for gene
      disruption in the founder generation (F0) by injecting sgRNA and Cas9
      ribonucleoprotein. Most embryos showed severe mutant phenotypes carrying high
      somatic mutation rates. Utilizing this founder analysis system, we examined the
      role of trbeta in metamorphosis. trbeta-disrupted pre-metamorphic tadpoles
      exhibited mixed responsiveness to exogenous TH. Specifically, gill resorption and
      activation of several TH-response genes, including trbeta itself and two protease
      genes, were impaired. However, hind limb outgrowth and induction of the TH
      response genes, klf9 and fra-2, were not affected by loss of trbeta Surprisingly,
      trbeta-disrupted tadpoles were able to undergo spontaneous metamorphosis
      normally, except for a slight delay in tail resorption. These results indicate
      TRbeta is not required but contributes to the timing of resorptive events of
      metamorphosis.

PMID- 29358167
TI  - Consultant is jailed for four years for sexual assaults on military recruits.

PMID- 29358166
TI  - An ancient conserved role for prion protein in learning and memory.
AB  - The misfolding of cellular prion protein (PrPC) to form PrP Scrapie (PrPSc) is an
      exemplar of toxic gain-of-function mechanisms inducing propagated protein
      misfolding and progressive devastating neurodegeneration. Despite this, PrPC
      function in the brain is also reduced and subverted during prion disease
      progression; thus understanding the normal function of PrPC in healthy brains is
      key. Disrupting PrPC in mice has led to a myriad of controversial functions that
      sometimes map onto disease symptoms, including a proposed role in memory or
      learning. Intriguingly, PrPC interaction with amyloid beta (Abeta) oligomers at
      synapses has also linked its function to Alzheimer's disease and dementia in
      recent years. We set out to test the involvement of PrPC in memory using a
      disparate animal model, the zebrafish. Here we document an age-dependent memory
      decline in prp2-/- zebrafish, pointing to a conserved and ancient role of PrPC in
      memory. Specifically, we found that aged (3-year-old) prp2-/- fish performed
      poorly in an object recognition task relative to age-matched prp2+/+ fish or 1
      year-old prp2-/- fish. Further, using a novel object approach (NOA) test, we
      found that aged (3-year-old) prp2-/- fish approached the novel object more than
      either age-matched prp2+/+ fish or 1-year-old prp2-/- fish, but did not have
      decreased anxiety when we tested them in a novel tank diving test. Taken
      together, the results of the NOA and novel tank diving tests suggest an altered
      cognitive appraisal of the novel object in the 3-year-old prp2-/- fish. The
      learning paradigm established here enables a path forward to study PrPC
      interactions of relevance to Alzheimer's disease and prion diseases, and to
      screen for candidate therapeutics for these diseases. The findings underpin a
      need to consider the relative contributions of loss- versus gain-of-function of
      PrPC during Alzheimer's and prion diseases, and have implications upon the
      prospects of several promising therapeutic strategies.

PMID- 29358168
TI  - Indian clinical guidelines lack scope, rigour, and quality, study finds.

PMID- 29358169
TI  - CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion.
AB  - The functional significance of the chemokine receptor CCR5 in human breast cancer
      epithelial cells is poorly understood. Here, we report that CCR5 expression in
      human breast cancer correlates with poor outcome. CCR5+ breast cancer epithelial
      cells formed mammospheres and initiated tumors with >60-fold greater efficiency
      in mice. Reintroduction of CCR5 expression into CCR5-negative breast cancer cells
      promoted tumor metastases and induced DNA repair gene expression and activity.
      CCR5 antagonists Maraviroc and Vicriviroc dramatically enhanced cell killing
      mediated by DNA-damaging chemotherapeutic agents. Single-cell analysis revealed
      CCR5 governs PI3K/Akt, ribosomal biogenesis, and cell survival signaling. As CCR5
      augments DNA repair and is reexpressed selectively on cancerous, but not normal
      breast epithelial cells, CCR5 inhibitors may enhance the tumor-specific
      activities of DNA damage response-based treatments, allowing a dose reduction of
      standard chemotherapy and radiation.Significance: This study offers a preclinical
      rationale to reposition CCR5 inhibitors to improve the treatment of breast
      cancer, based on their ability to enhance the tumor-specific activities of DNA
      damaging chemotherapies administered in that disease. Cancer Res; 78(7); 1657-71.
      (c)2018 AACR.

PMID- 29358170
TI  - 2-Hydroxyglutarate-Mediated Autophagy of the Endoplasmic Reticulum Leads to an
      Unusual Downregulation of Phospholipid Biosynthesis in Mutant IDH1 Gliomas.
AB  - Tumor metabolism is reprogrammed to meet the demands of proliferating cancer
      cells. In particular, cancer cells upregulate synthesis of the membrane
      phospholipids phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdE) in
      order to allow for rapid membrane turnover. Nonetheless, we show here that, in
      mutant isocitrate dehydrogenase 1 (IDHmut) gliomas, which produce the
      oncometabolite 2-hydroxyglutarate (2-HG), PtdCho and PtdE biosynthesis is
      downregulated and results in lower levels of both phospholipids when compared
      with wild-type IDH1 cells. 2-HG inhibited collagen-4-prolyl hydroxylase activity,
      leading to accumulation of misfolded procollagen-IV in the endoplasmic reticulum
      (ER) of both genetically engineered and patient-derived IDHmut glioma models. The
      resulting ER stress triggered increased expression of FAM134b, which mediated
      autophagic degradation of the ER (ER-phagy) and a reduction in the ER area.
      Because the ER is the site of phospholipid synthesis, ER-phagy led to reduced
      PtdCho and PtdE biosynthesis. Inhibition of ER-phagy via pharmacological or
      molecular approaches restored phospholipid biosynthesis in IDHmut glioma cells,
      triggered apoptotic cell death, inhibited tumor growth, and prolonged the
      survival of orthotopic IDHmut glioma-bearing mice, pointing to a potential
      therapeutic opportunity. Glioma patient biopsies also exhibited increased ER
      phagy and downregulation of PtdCho and PtdE levels in IDHmut samples compared
      with wild-type, clinically validating our observations. Collectively, this study
      provides detailed and clinically relevant insights into the functional link
      between oncometabolite-driven ER-phagy and phospholipid biosynthesis in IDHmut
      gliomas.Significance: Downregulation of phospholipid biosynthesis via ER-phagy is
      essential for proliferation and clonogenicity of mutant IDH1 gliomas, a finding
      with immediate therapeutic implications. Cancer Res; 78(9); 2290-304. (c)2018
      AACR.

PMID- 29358171
TI  - Small-Molecule Activators of Protein Phosphatase 2A for the Treatment of
      Castration-Resistant Prostate Cancer.
AB  - Primary prostate cancer is generally treatable by androgen deprivation therapy,
      however, later recurrences of castrate-resistant prostate cancer (CRPC) that are
      more difficult to treat nearly always occur due to aberrant reactivation of the
      androgen receptor (AR). In this study, we report that CRPC cells are particularly
      sensitive to the growth-inhibitory effects of reengineered tricyclic
      sulfonamides, a class of molecules that activate the protein phosphatase PP2A,
      which inhibits multiple oncogenic signaling pathways. Treatment of CRPC cells
      with small-molecule activators of PP2A (SMAP) in vitro decreased cellular
      viability and clonogenicity and induced apoptosis. SMAP treatment also induced an
      array of significant changes in the phosphoproteome, including most notably
      dephosphorylation of full-length and truncated isoforms of the AR and
      downregulation of its regulatory kinases in a dose-dependent and time-dependent
      manner. In murine xenograft models of human CRPC, the potent compound SMAP-2
      exhibited efficacy comparable with enzalutamide in inhibiting tumor formation.
      Overall, our results provide a preclinical proof of concept for the efficacy of
      SMAP in AR degradation and CRPC treatment.Significance: A novel class of small
      molecule activators of the tumor suppressor PP2A, a serine/threonine phosphatase
      that inhibits many oncogenic signaling pathways, is shown to deregulate the
      phosphoproteome and to destabilize the androgen receptor in advanced prostate
      cancer. Cancer Res; 78(8); 2065-80. (c)2018 AACR.

PMID- 29358173
TI  - Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free
      Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized
      Study.
AB  - We investigated the efficacy of a Wilms' tumor gene 1 (WT1) vaccine combined with
      gemcitabine (GEMWT1) and compared it with gemcitabine (GEM) monotherapy for
      advanced pancreatic ductal adenocarcinoma (PDAC) in a randomized phase II study.
      We randomly assigned HLA-A*02:01- or HLA-A*24:02-positive patients with advanced
      PDAC to receive GEMWT1 or GEM. We assessed WT1-specific immune responses via
      delayed-type hypersensitivity (DTH) to the WT1 peptide and a tetramer assay to
      detect WT1-specific cytotoxic T lymphocytes (WT1-CTL). Of 91 patients enrolled,
      85 were evaluable (GEMWT1: n = 42; GEM: n = 43). GEMWT1 prolonged progression
      free survival [PFS; hazard ratio (HR), 0.66; P = 0.084] and improved overall
      survival rate at 1 year (1-year OS%; GEMWT1: 35.7%; GEM: 20.9%). However, the
      difference in OS was not significant (HR: 0.82; P = 0.363). These effects were
      particularly evident in metastatic PDAC (PFS: HR 0.51, P = 0.0017; 1-year OS%:
      GEMWT1 27.3%; GEM 11.8%). The combination was well tolerated, with no unexpected
      serious adverse events. In patients with metastatic PDAC, PFS in the DTH-positive
      GEMWT1 group was significantly prolonged, with a better HR of 0.27 compared with
      the GEM group, whereas PFS in the DTH-negative GEMWT1 group was similar to that
      in the GEM group (HR 0.86; P = 0.001). DTH positivity was associated with an
      increase in WT1-CTLs induced by the WT1 vaccine. GEM plus the WT1 vaccine
      prolonged PFS and may improve 1-year OS% in advanced PDAC. These clinical effects
      were associated with the induction of WT1-specific immune responses. Cancer
      Immunol Res; 6(3); 1-12. (c)2018 AACR.

PMID- 29358174
TI  - Low-Density Lipoprotein Uptake Inhibits the Activation and Antitumor Functions of
      Human Vgamma9Vdelta2 T Cells.
AB  - Vgamma9Vdelta2 T cells, the main subset of gammadelta T lymphocytes in human
      peripheral blood, are endowed with antitumor functions such as cytotoxicity and
      IFNgamma production. These functions are triggered upon T-cell receptor-dependent
      activation by non-peptidic prenyl pyrophosphates ("phosphoantigens") that are
      selective agonists of Vgamma9Vdelta2 T cells, and which have been evaluated in
      clinical studies. Because phosphoantigens have shown interindividual variation in
      Vgamma9Vdelta2 T-cell activities, we asked whether metabolic resources, namely
      lipids such as cholesterol, could affect phosphoantigen-mediated Vgamma9Vdelta2 T
      cell activation and function. We show here that Vgamma9Vdelta2 T cells express
      the LDL receptor upon activation and take up LDL cholesterol. Resulting changes,
      such as decreased mitochondrial mass and reduced ATP production, correlate with
      downregulation of Vgamma9Vdelta2 T-cell activation and functionality. In
      particular, the expression of IFNgamma, NKG2D, and DNAM-1 were reduced upon LDL
      cholesterol treatment of phosphoantigen-expanded Vgamma9Vdelta2 T cells. As a
      result, their capacity to target breast cancer cells was compromised both in
      vitro and in an in vivo xenograft mouse model. Thus, this study describes the
      role of LDL cholesterol as an inhibitor of the antitumor functions of
      phosphoantigen-activated Vgamma9Vdelta2 T cells. Our observations have
      implications for therapeutic applications dependent on Vgamma9Vdelta2 T cells.
      Cancer Immunol Res; 6(4); 448-57. (c)2018 AACR.

PMID- 29358172
TI  - Selective mTORC2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and
      Survival.
AB  - Small-molecule inhibitors of the mTORC2 kinase (torkinibs) have shown efficacy in
      early clinical trials. However, the torkinibs under study also inhibit the other
      mTOR-containing complex mTORC1. While mTORC1/mTORC2 combined inhibition may be
      beneficial in cancer cells, recent reports describe compensatory cell survival
      upon mTORC1 inhibition due to loss of negative feedback on PI3K, increased
      autophagy, and increased macropinocytosis. Genetic models suggest that selective
      mTORC2 inhibition would be effective in breast cancers, but the lack of selective
      small-molecule inhibitors of mTORC2 have precluded testing of this hypothesis to
      date. Here we report the engineering of a nanoparticle-based RNAi therapeutic
      that can effectively silence the mTORC2 obligate cofactor Rictor. Nanoparticle
      based Rictor ablation in HER2-amplified breast tumors was achieved following
      intratumoral and intravenous delivery, decreasing Akt phosphorylation and
      increasing tumor cell killing. Selective mTORC2 inhibition in vivo, combined with
      the HER2 inhibitor lapatinib, decreased the growth of HER2-amplified breast
      cancers to a greater extent than either agent alone, suggesting that mTORC2
      promotes lapatinib resistance, but is overcome by mTORC2 inhibition. Importantly,
      selective mTORC2 inhibition was effective in a triple-negative breast cancer
      (TNBC) model, decreasing Akt phosphorylation and tumor growth, consistent with
      our findings that RICTOR mRNA correlates with worse outcome in patients with
      basal-like TNBC. Together, our results offer preclinical validation of a novel
      RNAi delivery platform for therapeutic gene ablation in breast cancer, and they
      show that mTORC2-selective targeting is feasible and efficacious in this disease
      setting.Significance: This study describes a nanomedicine to effectively inhibit
      the growth regulatory kinase mTORC2 in a preclinical model of breast cancer,
      targeting an important pathogenic enzyme in that setting that has been
      undruggable to date. Cancer Res; 78(7); 1845-58. (c)2018 AACR.

PMID- 29358175
TI  - Extracellular vesicle-mediated transfer of constitutively active MyD88L265P
      engages MyD88wt and activates signaling.
AB  - The link between inflammation and cancer is particularly strong in Waldenstrom
      macroglobulinemia (WM), a diffuse large B-cell lymphoma wherein the majority of
      patients harbor a constitutively active mutation in the innate immune-signaling
      adaptor myeloid differentiation primary response 88 (MyD88). MyD88Leu265Pro
      (MyD88L265P) constitutively triggers the myddosome assembly providing a survival
      signal for cancer cells. Here, we report detection and a functional role of MyD88
      in the extracellular vesicles (EVs) shed from WM cells. MyD88L265P was
      transferred via EVs into the cytoplasm of the recipient mast cells and
      macrophages, recruiting the endogenous MyD88 that triggered the activation of
      proinflammatory signaling in the absence of receptor activation. Additionally,
      internalization of EVs containing MyD88L265P was observed in mice with an effect
      on the bone marrow microenvironment. MyD88-loaded EVs were detected in the bone
      marrow aspirates of WM patients thus establishing the physiological role of EVs
      for MyD88L265P transmission and shaping of the proinflammatory microenvironment.
      Results establish the mechanism of transmission of signaling complexes via EVs to
      propagate inflammation as a new mechanism of intercellular communication.

PMID- 29358176
TI  - The potential role of gammadelta T cells after allogeneic HCT for leukemia.
AB  - Allogeneic hematopoetic stem cell transplantation (HCT) offers an option for
      patients with hematologic malignancies, in whom conventional standard therapies
      failed or are not effective enough to cure the disease. Successful HCT can
      restore functional hematopoiesis and immune function, and the new donor-derived
      immune system can exert a graft-versus-leukemia (GVL) effect. However, allogenic
      HCT can also be associated with serious risks for transplantation-related
      morbidities or mortalities such as graft-versus-host disease (GVHD) or life
      threatening infectious complications. GVHD is caused by alloreactive T
      lymphocytes, which express the alphabeta T-cell receptor, whereas lymphocytes
      expressing the gammadelta T-cell receptor are not alloreactive and do not induce
      GVHD but can exhibit potent antileukemia and anti-infectious activities.
      Therefore, gammadelta T cells are becoming increasingly interesting in allogeneic
      HCT, and clinical strategies to exploit the full function of these lymphocytes
      have been and are being developed. Such strategies comprise the in vivo
      activation of gammadelta T cells or subsets after HCT by certain drugs or
      antibodies or the ex vivo expansion and manipulation of either patient-derived or
      donor-derived gammadelta T cells and their subsets and the adoptive transfer of
      the ex vivo-activated lymphocytes. On the basis of the absence of dysregulated
      alloreactivity, such approaches could induce potent GVL effects in the absence of
      GVHD. The introduction of large-scale clinical methods to enrich, isolate,
      expand, and manipulate gammadelta T cells will facilitate future clinical studies
      that aim to exploit the full function of these beneficial nonalloreactive
      lymphocytes.

PMID- 29358177
TI  - Tyrosine kinase inhibitors and immune checkpoint blockade in allogeneic
      hematopoietic cell transplantation.
AB  - Advances in the prevention of graft-versus-host disease (GVHD) and opportunistic
      infection have improved survival after allogeneic hematopoietic cell
      transplantation (allo-HCT) in the past decade. However, few inroads have been
      made into the treatment or prevention of relapse of the underlying malignancy for
      which allo-HCT is being performed. The introduction of US Food and Drug
      Administration-approved agents with significant activity in a variety of
      hematologic malignancies provides an opportunity to evaluate these interventions
      in the allo-HCT setting. Some of the most promising new agents include tyrosine
      kinase inhibitors (TKIs) directed at bcr-abl, kinase inhibitors targeting fms
      like tyrosine kinase 3, and immune checkpoint inhibitors blocking both CTLA4 and
      PD-1. Data have emerged indicating potential efficacy of these agents in
      preventing or treating relapse, though definitive evidence remains elusive.
      However, potential toxicity can be considerable, highlighting the need for
      further clinical trials to define the therapeutic window. This review explores
      the immunologic and clinical consequence of treatment with both TKIs and
      checkpoint inhibitors in the peri- and post-allo-HCT setting.

PMID- 29358178
TI  - Introduction to a review series on strategies to improve GVL effects.

PMID- 29358180
TI  - Loss of Toll-like receptor 2 results in accelerated leukemogenesis in the NUP98
      HOXD13 mouse model of MDS.

PMID- 29358179
TI  - Strategies to activate NK cells to prevent relapse and induce remission following
      hematopoietic stem cell transplantation.
AB  - Natural killer (NK) cells are lymphocytes of innate immunity that respond to
      virus infected and tumor cells. After allogeneic transplantation, NK cells are
      the first reconstituting lymphocytes, but are dysfunctional. Manipulating this
      first wave of lymphocytes could be instrumental in reducing the 40% relapse rate
      following transplantation with reduced-intensity conditioning. NK cells express
      numerous activating and inhibitory receptors. Some recognize classical or
      nonclassical HLA class I ligands, others recognize class I-like ligands or
      unrelated ligands. Dominant in the NK-cell transplant literature are killer cell
      immunoglobulin-like receptors (KIRs), encoded on chromosome 19q. Inhibitory KIR
      recognition of the cognate HLA class I ligand is responsible for NK-cell
      education, which makes them tolerant of healthy cells, but responsive to
      unhealthy cells having reduced expression of HLA class I. KIR A and KIR B are
      functionally distinctive KIR haplotype groups that differ in KIR gene content.
      Allogeneic transplant donors having a KIR B haplotype and lacking a recipient HLA
      C epitope provide protection against relapse from acute myeloid leukemia.
      Cytomegalovirus infection stimulates and expands a distinctive NK-cell population
      that expresses the NKG2C receptor and exhibits enhanced effector functions. These
      adaptive NK cells display immune memory and methylation signatures like CD8 T
      cells. As potential therapy, NK cells, including adaptive NK cells, can be
      adoptively transferred with, or without, agents such as interleukin-15 that
      promote NK-cell survival. Strategies combining NK-cell infusions with CD16
      binding antibodies or immune engagers could make NK cells antigen specific.
      Together with checkpoint inhibitors, these approaches have considerable potential
      as anticancer therapies.

PMID- 29358181
TI  - Posttransplant chimeric antigen receptor therapy.
AB  - Therapeutic T-cell engineering is emerging as a powerful approach to treat
      refractory hematological malignancies. Its most successful embodiment to date is
      based on the use of second-generation chimeric antigen receptors (CARs) targeting
      CD19, a cell surface molecule found in most B-cell leukemias and lymphomas.
      Remarkable complete remissions have been obtained with autologous T cells
      expressing CD19 CARs in patients with relapsed, chemo-refractory B-cell acute
      lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma.
      Allogeneic CAR T cells may also be harnessed to treat relapse after allogeneic
      hematopoietic stem cell transplantation. However, the use of donor T cells poses
      unique challenges owing to potential alloreactivity. We review different
      approaches to mitigate the risk of causing or aggravating graft-versus-host
      disease (GVHD), including CAR therapies based on donor leukocyte infusion, virus
      specific T cells, T-cell receptor-deficient T cells, lymphoid progenitor cells,
      and regulatory T cells. Advances in CAR design, T-cell selection and gene editing
      are poised to enable the safe use of allogeneic CAR T cells without incurring
      GVHD.

PMID- 29358182
TI  - Blinatumomab for minimal residual disease in adults with B-cell precursor acute
      lymphoblastic leukemia.
AB  - Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in
      hematologic complete remission after multiagent therapy exhibit minimal residual
      disease (MRD) by reverse transcriptase-polymerase chain reaction or flow
      cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label,
      single-arm study, adults with B-cell precursor ALL in hematologic complete
      remission with MRD (>=10-3) received blinatumomab 15 ug/m2 per day by continuous
      IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic
      stem-cell transplantation any time after cycle 1. The primary end point was
      complete MRD response status after 1 cycle of blinatumomab. One hundred sixteen
      patients received blinatumomab. Eighty-eight (78%) of 113 evaluable patients
      achieved a complete MRD response. In the subgroup of 110 patients with Ph
      negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free
      survival (RFS) at 18 months was 54%. Median overall survival (OS) was 36.5
      months. In landmark analyses, complete MRD responders had longer RFS (23.6 vs 5.7
      months; P = .002) and OS (38.9 vs 12.5 months; P = .002) compared with MRD
      nonresponders. Adverse events were consistent with previous studies of
      blinatumomab. Twelve (10%) and 3 patients (3%) had grade 3 or 4 neurologic
      events, respectively. Four patients (3%) had cytokine release syndrome grade 1, n
      = 2; grade 3, n = 2), all during cycle 1. After treatment with blinatumomab in a
      population of patients with MRD-positive B-cell precursor ALL, a majority
      achieved a complete MRD response, which was associated with significantly longer
      RFS and OS compared with MRD nonresponders. This study is registered at
      www.clinicaltrials.gov as #NCT01207388.

PMID- 29358183
TI  - Clinical implications of cancer gene mutations in patients with chronic
      lymphocytic leukemia treated with lenalidomide.
AB  - Lenalidomide is clinically active in chronic lymphocytic leukemia (CLL), but its
      effectiveness in the context of the CLL mutational landscape is unknown. We
      performed targeted capture sequencing of 295 cancer genes in specimens from 102
      CLL patients with treatment-naive disease (TN patients) and 186 CLL patients with
      relapsed/refractory disease (R/R patients) who received lenalidomide-based
      therapy at our institution. The most frequently mutated gene was SF3B1 (15%),
      followed by NOTCH1 (14%) and TP53 (14%), with R/R patients having significantly
      more TP53 mutations than did TN patients. Among all lenalidomide-treated
      patients, del(17p) (P <= .001), del(11q) (P = .032), and complex karyotype (P =
      .022), along with mutations in TP53 (P <= .001), KRAS (P = .034), and DDX3X (P <=
      .001), were associated with worse overall response (OR). R/R patients with SF3B1
      and MGA mutations had significantly worse OR (P = .025 and .035, respectively).
      TN and R/R patients with del(17p) and TP53 mutations had worse overall survival
      (OS) and progression-free survival (PFS). In R/R patients, complex karyotype and
      SF3B1 mutations were associated with worse OS and PFS; DDX3X mutations were
      associated with worse PFS only. Weibull regression multivariate analysis revealed
      that TP53 aberrations (del(17p), TP53 mutation, or both), along with complex
      karyotype and SF3B1 mutations, were associated with worse OS in the R/R cohort.
      Taken together, cancer gene mutations in CLL contribute to the already
      comprehensive risk stratification and add to prognosis and response to treatment.
      The related trials were registered at www.clinicaltrials.gov as #NCT00267059,
      #NCT00535873, #NCT00759603, #NCT01446133, and #NCT01002755.

PMID- 29358184
TI  - Curcumin as an In Vivo Selective Intestinal Breast Cancer Resistance Protein
      Inhibitor in Cynomolgus Monkeys.
AB  - To estimate the clinical impact of pharmacokinetic modulation via breast cancer
      resistance protein (BCRP), in vivo approaches in nonclinical settings are desired
      in drug development. Clinical observation has identified curcumin as a promising
      candidate for in vivo selective BCRP inhibition, in addition to several well
      known inhibitors, such as lapatinib and pantoprazole. This study aimed to confirm
      the inhibitory efficacy of curcumin on gastrointestinal BCRP function in
      cynomolgus monkeys and to perform comparisons with lapatinib and pantoprazole.
      Oral area under the plasma concentration-time curve (AUC) and bioavailability of
      well known BCRP (sulfasalazine and rosuvastatin), P-glycoprotein (fexofenadine,
      aliskiren, and talinolol), and CYP3A (midazolam) substrates were investigated in
      the presence and absence of inhibitors. Oral exposures of sulfasalazine and
      rosuvastatin were markedly elevated by curcumin with minimal changes in systemic
      clearance, whereas pharmacokinetic alterations after fexofenadine, aliskiren, and
      talinolol oral exposure were limited. Curcumin increased oral midazolam exposure
      without affecting systemic clearance, presumably owing to partial inhibition of
      intestinal CYP3A. Lapatinib increased the oral AUC for sulfasalazine to a greater
      extent than curcumin did, whereas pantoprazole had a smaller effect. However,
      lapatinib also exerted significant effects on fexofenadine, failed to selectively
      discriminate between BCRP and P-glycoprotein inhibition, and had an effect on
      oral midazolam exposure comparable with that of curcumin. Thus, pharmacokinetic
      evaluation in monkeys demonstrated that pretreatment with curcumin as an in vivo
      selective BCRP inhibitor was more appropriate than pretreatment with lapatinib
      and pantoprazole for the assessment of the impact of BCRP on gastrointestinal
      absorption in nonrodent models.

PMID- 29358185
TI  - Stress echocardiography in contemporary clinical cardiology: practical
      considerations and accreditation.
AB  - Stress echocardiography is a widely utilised test in patients with known or
      suspected coronary artery disease (CAD), valvular heart disease and
      cardiomyopathies. Its advantages include the ubiquitous availability of
      echocardiography, lack of ionising radiation, choice of physiological or
      pharmacological stressors, good diagnostic accuracy and robust supporting
      evidence base. SE has evolved significantly as a technique over the past three
      decades and has benefitted considerably from improvements in overall image
      quality (superior resolution), machine technology (e.g. digital cine-loop
      acquisition and side-by-side image display) and development of second-generation
      ultrasound contrast agents that have improved reader confidence and diagnostic
      accuracy. The purpose of this article is to review the breadth of SE in
      contemporary clinical cardiology and discuss the recently launched British
      Society of Echocardiography (BSE) Stress Echocardiography accreditation scheme.

PMID- 29358186
TI  - A role for P2X4 receptors in lysosome function.

PMID- 29358187
TI  - Correction: The relationship between form and function throughout the history of
      excitation-contraction coupling.

PMID- 29358188
TI  - Globular C1q receptor (p33) binds and stabilizes pro-inflammatory MCP-1: a novel
      mechanism for regulation of MCP-1 production and function.
AB  - The protein gC1qR (globular C1q receptor), also named p33, was originally
      identified as a binding partner of the globular heads of C1q in the complement
      system. gC1qR/p33 is abundantly expressed in many cell types, but the functional
      importance of this protein is not completely understood. Here, we investigate the
      impact of gC1qR/p33 on the production and function of the pathophysiologically
      important chemokine monocyte chemoattractant protein-1 (MCP-1) and the underlying
      molecular mechanisms. Knockdown of gC1qR/p33 negatively regulated the production
      of MCP-1, but had no effect on the expression of transcript for MCP-1 in human
      periodontal ligament cells, suggesting a translational/post-translational
      mechanism of action. Laser scanning confocal microscopy showed considerable
      cytosolic co-localization of gC1qR/p33 and MCP-1, and co-immunoprecipitation
      disclosed direct physical interaction between gC1qR/p33 and MCP-1. Surface
      plasmon resonance analysis revealed a high-affinity binding (KD = 10.9 nM)
      between gC1qR/p33 and MCP-1. Using a transwell migration assay, we found that
      recombinant gC1qR/p33 enhances MCP-1-induced migration of human THP-1 monocytes,
      pointing to a functional importance of the interaction between gC1qR/p33 and MCP
      1. An in vitro assay revealed a rapid turnover of the MCP-1 protein and that
      gC1qR/p33 stabilizes MCP-1, hence preventing its degradation. We propose that
      endogenous gC1qR/p33 physically interacts with MCP-1 causing stabilization of the
      MCP-1 protein and stimulation of its activity in human periodontal ligament
      cells, suggesting a novel gC1qR/p33-mediated pro-inflammatory mechanism of
      action.

PMID- 29358189
TI  - CMS-G from Beta vulgaris ssp. maritima is maintained in natural populations
      despite containing an atypical cytochrome c oxidase.
AB  - While mitochondrial mutants of the respiratory machinery are rare and often
      lethal, cytoplasmic male sterility (CMS), a mitochondrially inherited trait that
      results in pollen abortion, is frequently encountered in wild populations. It
      generates a breeding system called gynodioecy. In Beta vulgaris ssp. maritima, a
      gynodioecious species, we found CMS-G to be widespread across the distribution
      range of the species. Despite the sequencing of the mitochondrial genome of CMS
      G, the mitochondrial sterilizing factor causing CMS-G is still unknown. By
      characterizing biochemically CMS-G, we found that the expression of several
      mitochondrial proteins is altered in CMS-G plants. In particular, Cox1, a core
      subunit of the cytochrome c oxidase (complex IV), is larger but can still
      assemble into complex IV. However, the CMS-G-specific complex IV was only
      detected as a stabilized dimer. We did not observe any alteration of the affinity
      of complex IV for cytochrome c; however, in CMS-G, complex IV capacity is
      reduced. Our results show that CMS-G is maintained in many natural populations
      despite being associated with an atypical complex IV. We suggest that the
      modified complex IV could incur the associated cost predicted by theoretical
      models to maintain gynodioecy in wild populations.

PMID- 29358190
TI  - Hospitalization Rates, Prevalence of Cardiovascular Manifestations, and Outcomes
      Associated With Sarcoidosis in the United States.
AB  - BACKGROUND: Recent trends of hospitalizations and in-hospital mortality are not
      well defined in sarcoidosis. We examined aforementioned trends and prevalence of
      cardiovascular manifestations and explored rates of implantable cardioverter
      defibrillator implantation in hospitalizations with sarcoidosis. METHODS AND
      RESULTS: Using data from the National Inpatient Sample, a retrospective
      population cohort from 2005 to 2014 was studied. To identify sarcoidosis, an
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) diagnosis code was used. We excluded hospitalizations with myocardial
      infarction, coronary artery disease, and ischemic cardiomyopathy. Cardiovascular
      manifestations were defined by the presence of diagnosis codes for conduction
      disorders, arrhythmias, heart failure, nonischemic cardiomyopathy, and pulmonary
      hypertension. A total of 609 051 sarcoidosis hospitalizations were identified,
      with an age of 55+/-14 years, 67% women, and 50% black. The number of sarcoidosis
      hospitalizations increased from 2005 through 2014 (138 versus 175 per 100 000,
      Ptrend<0.001). We observed declining trends of unadjusted in-hospital mortality
      (6.5 to 4.9 per 100 sarcoidosis hospitalizations, Ptrend<0.001). Overall ~31%
      (n=188 438) of sarcoidosis hospitalizations had coexistent cardiovascular
      manifestations of one or more type. Heart failure (~16%) and arrhythmias (~15%)
      were the most prevalent cardiovascular manifestations. Rates of implantable
      cardioverter-defibrillator placement were ~7.5 per 1000 sarcoidosis
      hospitalizations (Ptrend=0.95) during the study period. Black race was associated
      with 21% increased risk of in-hospital mortality (odds ratio, 1.21; 95%
      confidence interval, 1.16-1.27 [P<0.001]). CONCLUSIONS: Sarcoidosis
      hospitalizations have increased over the past decade with a myriad of coexistent
      cardiovascular manifestations. Black race is a significant predictor of in
      hospital mortality, which is declining. Further efforts are needed to improve
      care in view of low implantable cardioverter-defibrillator rates in sarcoidosis.

PMID- 29358191
TI  - A Disintegrin and Metalloprotease-22 Attenuates Hypertrophic Remodeling in Mice
      Through Inhibition of the Protein Kinase B Signaling Pathway.
AB  - BACKGROUND: Severe cardiac hypertrophy can lead to cardiac remodeling and even
      heart failure in the end, which is a leading cause of cardiovascular disease
      related mortality worldwide. A disintegrin and metalloprotease-22 (ADAM22), a
      member of the transmembrane and secreted metalloendopeptidase family,
      participates in many biological processes, including those in the cardiovascular
      system. However, there is no explicit information on whether ADAM22 can regulate
      the process of cardiac hypertrophy; the effects that ADAM22 exerts in cardiac
      hypertrophy remain elusive. METHODS AND RESULTS: We observed significantly
      increased ADAM22 expression in failing hearts from patients with dilated
      cardiomyopathy and hypertrophic cardiomyopathy; the same trend was observed in
      mice induced by transaortic constriction and in neonatal rat cardiomyocytes
      treated by angiotensin II. Therefore, we constructed both cardiac-specific ADAM22
      overexpression and knockout mice. At 4 weeks after transaortic constriction,
      cardiac-specific ADAM22 knockout, by the CRISPR/Cas9 (clustered regularly
      interspaced palindromic repeat (CRISPR)-Cas9) system, deteriorated the severity
      of cardiac hypertrophy in mice, whereas cardiac-specific ADAM22 overexpression
      mitigated the degrees of cardiac hypertrophy in mice. Similarly, altered ADAM22
      expression modulated the angiotensin II-mediated cardiomyocyte hypertrophy in
      neonatal rat cardiomyocytes. After screening several signaling pathways, we found
      ADAM22 played a role in inhibition of protein kinase B (AKT) activation. Under
      the cardiac-specific ADAM22 knockout background, AKT activation was enhanced in
      transaortic constriction-induced mice and angiotensin II-stimulated neonatal rat
      cardiomyocytes, with a severe degree of cardiac hypertrophy. Treatment of a
      specific AKT inhibitor attenuated the transaortic constriction-enhanced AKT
      activation and cardiac hypertrophy in mice. CONCLUSIONS: The findings
      demonstrated that ADAM22 negatively regulates the AKT activation and the process
      of cardiac hypertrophy and may provide new insights into the pathobiological
      features of cardiac hypertrophy.

PMID- 29358192
TI  - Circulating Circles Predict Postoperative Atrial Fibrillation.

PMID- 29358193
TI  - Relationship of Arterial Stiffness Index and Pulse Pressure With Cardiovascular
      Disease and Mortality.
AB  - BACKGROUND: Vascular aging results in stiffer arteries and may have a role in the
      development of cardiovascular disease (CVD). Arterial stiffness index (ASI),
      measured by finger photoplethysmography, and pulse pressure (PP) are 2
      independent vascular aging indices. We investigated whether ASI or PP predict new
      onset CVD and mortality in a large community-based population. METHODS AND
      RESULTS: We studied 169 613 UK Biobank participants (mean age 56.8 years; 45.8%
      males) who underwent ASI measurement and blood pressure measurement for PP
      calculation. Mean+/-SD ASI was 9.30+/-3.1 m/s and mean+/-SD PP was 50.98+/-13.2
      mm Hg. During a median disease follow-up of 2.8 years (interquartile range 1.4
      4.0), 18 190 participants developed CVD, of which 1587 myocardial infarction
      (MI), 4326 coronary heart disease, 1192 heart failure, and 1319 stroke. During a
      median mortality follow-up of 6.1 years (interquartile range 5.8-6.3), 3678
      participants died, of which 1180 of CVD. Higher ASI was associated with increased
      risk of overall CVD (unadjusted hazard ratio 1.27; 95% confidence interval [CI],
      1.25-1.28), myocardial infarction (1.38; 95% CI, 1.32-1.44), coronary heart
      disease (1.31; 95% CI, 1.27-1.34), and heart failure (1.31; 95% CI 1.24-1.37).
      ASI also predicted mortality (all-cause, CVD, other). Higher PP was associated
      with overall CVD (1.57; 95% CI, 1.55-1.59), myocardial infarction (1.48; 95% CI,
      1.42-1.54), coronary heart disease (1.47; 95% CI, 1.43-1.50), heart failure
      (1.47; 95% CI, 1.40-1.55), and CVD mortality (1.47; 95% CI, 1.40-1.55). PP
      improved risk reclassification of CVD in a non-laboratory-based Framingham Risk
      Score by 5.4%, ASI by 2.3%. CONCLUSIONS: ASI and PP are independent predictors of
      CVD and mortality outcomes. Although both improved risk prediction for new-onset
      disease, PP appears to have a larger clinical value than ASI.

PMID- 29358195
TI  - National Trends in Nonstatin Use and Expenditures Among the US Adult Population
      From 2002 to 2013: Insights From Medical Expenditure Panel Survey.
AB  - BACKGROUND: Evidence supporting nonstatin lipid-lowering therapy in
      atherosclerotic cardiovascular disease risk reduction is variable. We aim to
      examine nonstatin utilization and expenditures in the United States between 2002
      and 2013. METHODS AND RESULTS: We used the Medical Expenditure Panel Survey
      database to estimate national trends in nonstatin use and cost (total and out-of
      pocket, adjusted to 2013 US dollars using a gross domestic product deflator)
      among adults 40 years or older. Nonstatin users increased from 3 million (2.5%)
      in 2002-2003 (20.1 million prescriptions) to 8 million (5.6%) in 2012-2013 (45.8
      million prescriptions). Among adults with atherosclerotic cardiovascular disease,
      nonstatin use increased from 7.5% in 2002-2003 to 13.9% in 2012-2013 after
      peaking at 20.3% in 2006-2007. In 2012-2013, 15.9% of high-intensity statin users
      also used nonstatins, versus 9.7% of low/moderate-intensity users and 3.6% of
      statin nonusers. Nonstatin use was significantly lower among women (odds ratio
      0.80; 95% confidence interval 0.75-0.86), racial/ethnic minorities (odds ratio
      0.41; 95% confidence interval 0.36-0.47), and the uninsured (odds ratio 0.47; 95%
      confidence interval 0.40-0.56). Total nonstatin expenditures increased from $1.7
      billion (out-of-pocket cost, $0.7 billion) in 2002-2003 to $7.9 billion (out-of
      pocket cost $1.6 billion) in 2012-2013, as per-user nonstatin expenditure
      increased from $550 to $992. Nonstatin expenditure as a proportion of all lipid
      lowering therapy expenditure increased 4-fold from 8% to 32%. CONCLUSIONS:
      Between 2002 and 2013, nonstatin use increased by 124%, resulting in a 364%
      increase in nonstatin-associated expenditures.

PMID- 29358194
TI  - Relationship of High-Density Lipoprotein Cholesterol With Renal Function in
      Patients Treated With Atorvastatin.
AB  - BACKGROUND: It is not known whether the concentration of high-density lipoprotein
      (HDL) cholesterol is related to renal function in statin-treated patients. We
      therefore investigated whether HDL cholesterol levels predicted renal function in
      atorvastatin-treated patients in the TNT (Treating to New Targets) trial. METHODS
      AND RESULTS: A total of 9542 participants were included in this analysis. Renal
      function was assessed by estimated glomerular filtration rate (eGFR). HDL
      cholesterol levels at month 3 were used as this is the time point at which on
      treatment HDL cholesterol levels became stable. Among 6319 participants with a
      normal eGFR (>=60 mL/min per 1.73 m2) at baseline, higher HDL cholesterol levels
      at month 3 were significantly associated with lower risk of decline in eGFR (ie,
      having eGFR <60 mL/min per 1.73 m2) during follow-up (HR of 1.04, 0.88, 0.85, and
      0.77 for HDL cholesterol quintiles 2, 3, 4, and 5, respectively, relative to
      quintile 1, P for trend=0.006). Among 3223 participants with an eGFR (<60 mL/min
      per 1.73 m2) at baseline, higher HDL cholesterol levels at month 3 had less
      impact on eGFR during follow-up, with statistical significance observed only when
      analyzing HDL cholesterol levels as a continuous variable (P=0.043), but not as a
      categorical quintile variable (P for trend=0.27). CONCLUSIONS: In patients
      treated with atorvastatin, higher HDL cholesterol levels were associated with
      lower risk of eGFR decline in patients with normal eGFR at baseline. However,
      further study is needed to establish whether there is any causal relationship
      between HDLs and renal function. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT00327691.

PMID- 29358196
TI  - The Latest in Resuscitation Science Research: Highlights from the American Heart
      Association's 2017 Resuscitation Science Symposium.

PMID- 29358197
TI  - Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model
      of Heart Failure.
AB  - BACKGROUND: Myocardial infarction increases the risk of heart failure (HF) and
      atrial fibrillation. Renal denervation (RDN) might suppress the development of
      atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN
      in the suppression of atrial fibrillation in a HF model after myocardial
      infarction. METHODS AND RESULTS: HF rabbits were created 4 weeks after coronary
      ligation. Rabbits were classified into 3 groups: normal control (n=10), HF
      (n=10), and HF-RDN (n=6). Surgical and chemical RDN were approached through
      midabdominal incisions in HF-RDN. Left anterior descending coronary artery in HF
      and HF-RDN was ligated to create myocardial infarction. After
      electrophysiological study, the rabbits were euthanized and the left atrial
      appendage was harvested for real-time polymerase chain reaction analysis and
      Trichrome stain. Left atrial dimension and left ventricular mass were smaller in
      HF-RDN by echocardiography compared with HF. Attenuated atrial fibrosis and
      tyrosine hydroxylase levels were observed in HF-RDN compared with HF. The mRNA
      expressions of Cav1.2, Nav1.5, Kir2.1, KvLQT1, phosphoinositide 3-kinase, AKT,
      and endothelial nitric oxide synthase in HF-RDN were significantly higher
      compared with HF. The effective refractory period and action potential duration
      of HF-RDN were significantly shorter compared with HF. Decreased atrial
      fibrillation inducibility was noted in HF-RDN compared with HF (50% versus 100%,
      P<0.05). CONCLUSIONS: RDN reversed atrial electrical and structural remodeling,
      and suppressed the atrial fibrillation inducibility in an ischemic HF model. The
      beneficial effect of RDN may be related to prevention of the downregulation of
      the phosphoinositide 3-kinase/AKT/endothelial nitric oxide synthase signaling
      pathway.

PMID- 29358199
TI  - The need for health in all policies in Canada.

PMID- 29358198
TI  - Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and
      Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial
      Infarction.
AB  - BACKGROUND: Transplantation of adventitial pericytes (APCs) promotes cardiac
      repair in murine models of myocardial infarction. The aim of present study was to
      confirm the benefit of APC therapy in a large animal model. METHODS AND RESULTS:
      We performed a blind, randomized, placebo-controlled APC therapy trial in a swine
      model of reperfused myocardial infarction. A first study used human APCs (hAPCs)
      from patients undergoing coronary artery bypass graft surgery. A second study
      used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction
      as assessed by cardiac magnetic resonance imaging and (2) myocardial
      vascularization and fibrosis as determined by immunohistochemistry.
      Transplantation of hAPCs reduced fibrosis but failed to improve the other
      efficacy end points. Incompatibility of the xenogeneic model was suggested by the
      occurrence of a cytotoxic response following in vitro challenge of hAPCs with
      swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted
      hearts. We next considered sAPCs as an alternative. Flow cytometry,
      immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a
      surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary
      density and fibrosis but did not improve cardiac magnetic resonance imaging
      indices of contractility. Transplanted cells were detected in the border zone.
      CONCLUSIONS: Immunologic barriers limit the applicability of a xenogeneic swine
      model to assess hAPC efficacy. On the other hand, we newly show that
      transplantation of allogeneic sAPCs is feasible, safe, and immunologically
      acceptable. The approach induces proangiogenic and antifibrotic benefits, though
      these effects were not enough to result in functional improvements.

PMID- 29358200
TI  - Effect of provincial spending on social services and health care on health
      outcomes in Canada: an observational longitudinal study.
AB  - BACKGROUND: Escalating health care spending is a concern in Western countries,
      given the lack of evidence of a direct connection between spending and
      improvements in health. We aimed to determine the association between spending on
      health care and social programs and health outcomes in Canada. METHODS: We used
      retrospective data from Canadian provincial expenditure reports, for the period
      1981 to 2011, to model the effects of social and health spending (as a ratio,
      social/health) on potentially avoidable mortality, infant mortality and life
      expectancy. We used linear regressions, accounting for provincial fixed effects
      and time, and controlling for confounding variables at the provincial level.
      RESULTS: A 1-cent increase in social spending per dollar spent on health was
      associated with a 0.1% (95% confidence interval [CI] 0.04% to 0.16%) decrease in
      potentially avoidable mortality and a 0.01% (95% CI 0.01% to 0.02%) increase in
      life expectancy. The ratio had a statistically nonsignificant relationship with
      infant mortality (p = 0.2). INTERPRETATION: Population-level health outcomes
      could benefit from a reallocation of government dollars from health to social
      spending, even if total government spending were left unchanged. This result is
      consistent with other findings from Canada and the United States.

PMID- 29358202
TI  - Hoarseness of unclear origin in adults.

PMID- 29358201
TI  - Management of osteoarthritis of the knee in younger patients.

PMID- 29358203
TI  - Muscle weakness related to herpes zoster.

PMID- 29358204
TI  - Cultural competency and culturally safe clinical care.

PMID- 29358205
TI  - Not all Polysporin products contain lidocaine.

PMID- 29358206
TI  - Growing consensus on link between strep and obsessive-compulsive disorder.

PMID- 29358207
TI  - Blood-delivering drones saving lives in Africa and maybe soon in Canada.

PMID- 29358208
TI  - New hope for unsanctioned safe injection site.

PMID- 29358209
TI  - Reducing the cost of inequality.

PMID- 29358210
TI  - The adherens junction-associated LIM domain protein Smallish regulates epithelial
      morphogenesis.
AB  - In epithelia, cells adhere to each other in a dynamic fashion, allowing the cells
      to change their shape and move along each other during morphogenesis. The
      regulation of adhesion occurs at the belt-shaped adherens junction, the zonula
      adherens (ZA). Formation of the ZA depends on components of the Par-atypical PKC
      (Par-aPKC) complex of polarity regulators. We have identified the Lin11, Isl-1,
      Mec-3 (LIM) protein Smallish (Smash), the orthologue of vertebrate LMO7, as a
      binding partner of Bazooka/Par-3 (Baz), a core component of the Par-aPKC complex.
      Smash also binds to Canoe/Afadin and the tyrosine kinase Src42A and localizes to
      the ZA in a planar polarized fashion. Animals lacking Smash show loss of planar
      cell polarity (PCP) in the embryonic epidermis and reduced cell bond tension,
      leading to severe defects during embryonic morphogenesis of epithelial tissues
      and organs. Overexpression of Smash causes apical constriction of epithelial
      cells. We propose that Smash is a key regulator of morphogenesis coordinating PCP
      and actomyosin contractility at the ZA.

PMID- 29358211
TI  - The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63
      ubiquitination of RhoB.
AB  - RhoGTPases control endothelial cell (EC) migration, adhesion, and barrier
      formation. Whereas the relevance of RhoA for endothelial barrier function is
      widely accepted, the role of the RhoA homologue RhoB is poorly defined. RhoB and
      RhoA are 85% identical, but RhoB's subcellular localization and half-life are
      uniquely different. Here, we studied the role of ubiquitination for the function
      and stability of RhoB in primary human ECs. We show that the K63
      polyubiquitination at lysine 162 and 181 of RhoB targets the protein to
      lysosomes. Moreover, we identified the RING E3 ligase complex Cullin-3-Rbx1
      KCTD10 as key modulator of endothelial barrier integrity via its regulation of
      the ubiquitination, localization, and activity of RhoB. In conclusion, our data
      show that ubiquitination controls the subcellular localization and lysosomal
      degradation of RhoB and thereby regulates the stability of the endothelial
      barrier through control of RhoB-mediated EC contraction.

PMID- 29358212
TI  - Regulation of intercellular TARGET OF MONOPTEROS 7 protein transport in the
      Arabidopsis root.
AB  - Intercellular communication coordinates hypophysis establishment in the
      Arabidopsis embryo. Previously, TARGET OF MONOPTEROS 7 (TMO7) was reported to be
      transported to the hypophysis, the founder cell of the root cap, and RNA
      suppression experiments implicated its function in embryonic root development.
      However, the protein properties and mechanisms mediating TMO7 protein transport,
      and the role the movement plays in development remained unclear. Here, we report
      that in the post-embryonic root, TMO7 and its close relatives are transported
      into the root cap through plasmodesmata in a sequence-dependent manner. We also
      show that nuclear residence is crucial for TMO7 transport, and postulate that
      modification, potentially phosphorylation, labels TMO7 for transport.
      Additionally, three novel CRISPR/Cas9-induced tmo7 alleles confirmed a role in
      hypophysis division, but suggest complex redundancies with close relatives in
      root formation. Finally, we demonstrate that TMO7 transport is biologically
      meaningful, as local expression partially restores hypophysis division in a
      plasmodesmal protein transport mutant. Our study identifies motifs and amino
      acids that are pivotal for TMO7 protein transport, and establishes the importance
      of TMO7 in hypophysis and root development.

PMID- 29358213
TI  - Nodal induces sequential restriction of germ cell factors during primordial germ
      cell specification.
AB  - Specification of the germ cell lineage is required for sexual reproduction in
      animals. The mechanism of germ cell specification varies among animals but
      roughly clusters into either inherited or inductive mechanisms. The inductive
      mechanism, the use of cell-cell interactions for germ cell specification, appears
      to be the ancestral mechanism in animal phylogeny, yet the pathways responsible
      for this process are only recently surfacing. Here, we show that germ cell
      factors in the sea star initially are present broadly, then become restricted
      dorsally and then in the left side of the embryo where the germ cells form a
      posterior enterocoel. We find that Nodal signaling is required for the
      restriction of two germ cell factors, Nanos and Vasa, during the early
      development of this animal. We learned that Nodal inhibits germ cell factor
      accumulation in three ways including: inhibition of specific transcription,
      degradation of specific mRNAs and inhibition of tissue morphogenesis. These
      results document a signaling mechanism required for the sequential restriction of
      germ cell factors, which causes a specific set of embryonic cells to become the
      primordial germ cells.

PMID- 29358214
TI  - Identification of jellyfish neuropeptides that act directly as oocyte maturation
      inducing hormones.
AB  - Oocyte meiotic maturation is crucial for sexually reproducing animals, and its
      core cytoplasmic regulators are highly conserved between species. By contrast,
      the few known maturation-inducing hormones (MIHs) that act on oocytes to initiate
      this process are highly variable in their molecular nature. Using the hydrozoan
      jellyfish species Clytia and Cladonema, which undergo oocyte maturation in
      response to dark-light and light-dark transitions, respectively, we deduced
      amidated tetrapeptide sequences from gonad transcriptome data and found that
      synthetic peptides could induce maturation of isolated oocytes at nanomolar
      concentrations. Antibody preabsorption experiments conclusively demonstrated that
      these W/RPRPamide-related neuropeptides account for endogenous MIH activity
      produced by isolated gonads. We show that the MIH peptides are synthesised by
      neural-type cells in the gonad, are released following dark-light/light-dark
      transitions, and probably act on the oocyte surface. They are produced by male as
      well as female jellyfish and can trigger both sperm and egg release, suggesting a
      role in spawning coordination. We propose an evolutionary link between hydrozoan
      MIHs and the neuropeptide hormones that regulate reproduction upstream of MIHs in
      bilaterian species.

PMID- 29358216
TI  - Fishing out oocyte maturation-inducing hormones.

PMID- 29358217
TI  - Homeostatic Response of Mouse renin Gene Transcription in a Hypertensive
      Environment Is Mediated by a Novel 5' Enhancer.
AB  - The renin-angiotensin system plays an essential role in blood pressure
      homeostasis. Because renin activity is reflected as a blood pressure phenotype,
      its gene expression in the kidney is tightly regulated by a feedback mechanism;
      i.e., renin gene transcription is suppressed in a hypertensive state. To address
      the molecular mechanisms controlling hypertension-responsive mouse renin (mRen)
      gene regulation, we deleted either 5' (17-kb) or 3' (78-kb) regions of the
      endogenous mRen gene and placed the animals in a hypertensive environment. While
      the mRen gene bearing the 3' deletion was appropriately downregulated, the one
      bearing the 5' deletion lost this hypertension responsiveness. Because the 17-kb
      sequence exhibited enhancer activity in vivo and in vitro, we narrowed down the
      enhancer to a 2.3-kb core using luciferase assays in As4.1 cells. When this 2.3
      kb sequence was removed from the endogenous mRen gene in the mouse, its basal
      expression was dramatically reduced, and the hypertension responsiveness was
      significantly attenuated. Furthermore, we demonstrated that the angiotensin II
      signal played an important role in mRen gene suppression. We propose that in a
      hypertensive environment, the activity of this novel enhancer is attenuated, and,
      as a consequence, mRen gene transcription is suppressed to maintain blood
      pressure.

PMID- 29358218
TI  - TCF7/TCF1 feedback controls osteocalcin signaling in brown adipocytes independent
      of canonical WNT/beta-catenin pathway.
AB  - Osteocalcin has recently been shown to regulate energy homeostasis through
      multiple pathways. Adipose tissue is a main organ of energy metabolism, and
      administration of recombinant osteocalcin in mice promoted energy consumption,
      thus counteracting obesity and glucose intolerance. The regulation of osteocalcin
      in islet beta cells has been well documented; however, it is unknown whether
      osteocalcin can also act on adipocytes, and if does, how it functions. Here, we
      provided evidence to demonstrate a specific role for osteocalcin in brown
      adipocyte thermogenesis. Importantly, expression of Gprc6a gene encoding a G
      protein-coupled receptor as osteocalcin receptor was activated by brown-fat-like
      differentiation. Moreover, Gprc6a expression could be further potentiated by
      osteocalcin. Meanwhile, overexpression and knockdown experiments validated its
      crucial role in osteocalcin-mediated thermogenic genes' activation. For the first
      time, we identified Tcf7 and Wnt3a as putative targets for osteocalcin signaling.
      TCF7 belongs to TCF/LEF1 family DNA binding factors crucial for canonical
      WNT/beta-catenin pathway; however, TCF7 modulates Gprc6a and Ucp1 promoter
      activation independent of beta-catenin. Further studies revealed that
      thermogenesis coactivator PRDM16 and histone demethylase LSD1 might be required
      for TCF7 activity. Hence, our study described a TCF7-dependent feedback control
      of osteocalcin-GPRC6A axis in brown adipocyte physiologies.

PMID- 29358219
TI  - Consent and the ethical duty to participate in health data research.
AB  - The predominant view is that a study using health data is observational research
      and should require individual consent unless it can be shown that gaining consent
      is impractical. But recent arguments have been made that citizens have an ethical
      obligation to share their health information for research purposes. In our view,
      this obligation is sufficient ground to expand the circumstances where secondary
      use research with identifiable health information is permitted without explicit
      subject consent. As such, for some studies the Institutional Review
      Board/Research Ethics Committee review process should not assess the practicality
      of gaining consent for data use. Instead the review process should focus on
      assessing the public good of the research, public engagement and transparency.

PMID- 29358215
TI  - The hematopoietic stem cell niche: from embryo to adult.
AB  - Hematopoietic stem cells (HSCs) develop in discrete anatomical niches, migrating
      during embryogenesis from the aorta-gonad-mesonephros (AGM) region to the fetal
      liver, and finally to the bone marrow, where most HSCs reside throughout adult
      life. These niches provide supportive microenvironments that specify, expand and
      maintain HSCs. Understanding the constituents and molecular regulation of HSC
      niches is of considerable importance as it could shed new light on the
      mechanistic principles of HSC emergence and maintenance, and provide novel
      strategies for regenerative medicine. However, controversy exists concerning the
      cellular complexity of the bone marrow niche, and our understanding of the
      different HSC niches during development remains limited. In this Review, we
      summarize and discuss what is known about the heterogeneity of the HSC niches at
      distinct stages of their ontogeny, from the embryo to the adult bone marrow,
      drawing predominantly on data from mouse studies.

PMID- 29358222
TI  - Carcinogen Exposure among Canadian Tobacco Users: Changes in NNK Exposure from
      2007-2009 through 2012-2013.
AB  - Background: Tobacco-specific nitrosamines (TSNAs) are a class of carcinogens
      found in tobacco products, whose levels can vary considerably depending on
      tobacco blends and manufacturing processes. The current study examined whether
      recent increases in levels of the TSNA NNK [4-(methylnitrosamino-1-(3-pyridyl)-1
      butanone] in Canadian cigarettes translated into differences in exposure among
      Canadian tobacco users.Methods: Nationally representative data from the Canadian
      Health Measures Survey (CHMS) were used to measure levels of total urinary NNAL
      [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol], a metabolite of the TSNA NNK,
      among tobacco users. Data from CHMS Cycle 3 (2012-13) were used to examine NNAL,
      and linear regression was used to examine predictors. Data from CHMS Cycle 1
      (2007-09) and Cycle 3 (2012-13) were used to examine changes in NNAL over
      time.Results: From 2007-2009 through 2012-2013, levels of creatinine-corrected
      NNAL increased by 64% (P < 0.0001). Levels of NNAL in 2012-2013 were higher among
      older respondents (P = 0.04), among females (P = 0.03), among respondents
      identifying as "white" and "Aboriginal" (P < 0.0001), and among those with
      greater daily cigarette consumption (P < 0.001), as well as greater levels of
      urinary free cotinine (P < 0.0001) and urinary creatinine (P <
      0.0001).Conclusions: The findings indicate that exposure to the TSNA NNK among
      Canadian tobacco users has increased considerably from 2007-2009 through 2012
      2013, in parallel to changes in TSNA levels in Canadian cigarettes. In the
      absence of epidemiologic data, it is unclear whether this change translates into
      increased risk.Impact: The study findings have potential implications for tobacco
      manufacturers, who bear a responsibility to reduce levels of tobacco carcinogens
      to the full extent possible. Cancer Epidemiol Biomarkers Prev; 27(3); 262-7.
      (c)2018 AACR.

PMID- 29358221
TI  - Sustained Formation of Nitroglycerin-Derived Nitric Oxide by Aldehyde
      Dehydrogenase-2 in Vascular Smooth Muscle without Added Reductants: Implications
      for the Development of Nitrate Tolerance.
AB  - According to current views, oxidation of aldehyde dehydrogenase-2 (ALDH2) during
      glyceryltrinitrate (GTN) biotransformation is essentially involved in vascular
      nitrate tolerance and explains the dependence of this reaction on added thiols.
      Using a novel fluorescent intracellular nitric oxide (NO) probe expressed in
      vascular smooth muscle cells (VSMCs), we observed ALDH2-catalyzed formation of NO
      from GTN in the presence of exogenously added dithiothreitol (DTT), whereas only
      a short burst of NO, corresponding to a single turnover of ALDH2, occurred in the
      absence of DTT. This short burst of NO associated with oxidation of the reactive
      C302 residue in the active site was followed by formation of low-nanomolar NO,
      even without added DTT, indicating slow recovery of ALDH2 activity by an
      endogenous reductant. In addition to the thiol-reversible oxidation of ALDH2,
      thiol-refractive inactivation was observed, particularly under high-turnover
      conditions. Organ bath experiments with rat aortas showed that relaxation by GTN
      lasted longer than that caused by the NO donor diethylamine/NONOate, in line with
      the long-lasting nanomolar NO generation from GTN observed in VSMCs. Our results
      suggest that an endogenous reductant with low efficiency allows sustained
      generation of GTN-derived NO in the low-nanomolar range that is sufficient for
      vascular relaxation. On a longer time scale, mechanism-based, thiol-refractive
      irreversible inactivation of ALDH2, and possibly depletion of the endogenous
      reductant, will render blood vessels tolerant to GTN. Accordingly, full
      reactivation of oxidized ALDH2 may not occur in vivo and may not be necessary to
      explain GTN-induced vasodilation.

PMID- 29358220
TI  - Caveolins as Regulators of Stress Adaptation.
AB  - Caveolins have been recognized over the past few decades as key regulators of
      cell physiology. They are ubiquitously expressed and regulate a number of
      processes that ultimately impact efficiency of cellular processes. Though not
      critical to life, they are central to stress adaptation in a number of organs.
      The following review will focus specifically on the role of caveolin in stress
      adaptation in the heart, brain, and eye, three organs that are susceptible to
      acute and chronic stress and that show as well declining function with age. In
      addition, we consider some novel molecular mechanisms that may account for this
      stress adaptation and also offer potential to drive the future of caveolin
      research.

PMID- 29358224
TI  - Total Nut, Tree Nut, Peanut, and Peanut Butter Consumption and the Risk of
      Pancreatic Cancer in the Netherlands Cohort Study.
AB  - Background: Nut intake has been associated with decreased cancer-related
      mortality, but few studies have examined the potential of nuts in the
      chemoprevention of pancreatic cancer. We prospectively investigated the
      association of total nut, tree nut, peanut, and peanut butter consumption with
      pancreatic cancer risk.Methods: In the Netherlands Cohort Study, 120,852 men and
      women completed a baseline questionnaire, including a food frequency
      questionnaire, in 1986. After 20.3 years of follow-up, 583 incident pancreatic
      cancer cases, including 349 microscopically confirmed pancreatic cancer (MCPC)
      cases, were included in multivariable case-cohort analyses.Results: Increased
      total nut consumption was associated with a nonsignificantly decreased MCPC risk
      in men [HR (95% confidence interval) for 10+ g/d vs. nonconsumers = 0.72 (0.47
      1.11), Ptrend = 0.163]. No clear association was found in women. For tree nut and
      peanut consumption, nonsignificant inverse associations were observed in men. In
      women, no or unclear associations were found for tree nut and peanut consumption.
      Peanut butter intake was related to a significantly reduced risk of MCPC in men
      [HR (95% confidence interval) for 5+ g/d vs. nonconsumers = 0.53 (0.28-1.00),
      Ptrend = 0.047], but this relation was not clear in women. Evidence for a
      nonlinear dose-response relation with MCPC was found for tree nut intake only.
      The associations were weaker when looking at total pancreatic cancer.Conclusions:
      Our results suggest that nuts and peanut butter might reduce pancreatic cancer
      risk in men. In women, no or unclear associations were found.Impact: Nut
      consumption might reduce the risk of pancreatic cancer in men. Cancer Epidemiol
      Biomarkers Prev; 27(3); 274-84. (c)2018 AACR.

PMID- 29358223
TI  - Marine omega-3 Polyunsaturated Fatty Acid and Fish Intake after Colon Cancer
      Diagnosis and Survival: CALGB 89803 (Alliance).
AB  - Background: Marine omega-3 polyunsaturated fatty acids (PUFAs), primarily found
      in dark fish, may prevent colorectal cancer progression, in part through
      inhibition of prostaglandin-endoperoxide synthase 2 (PTGS2). However, data in
      humans are limited.Methods: We examined marine omega-3 PUFAs and fish intake and
      survival among 1,011 colon cancer patients enrolled in Cancer and Leukemia Group
      B 89803 between 1999 and 2001 and followed through 2009. Diet was assessed during
      and 6 months after chemotherapy. We used Cox proportional hazards regression to
      estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free
      (DFS), recurrence-free (RFS), and overall survival (OS).Results: We observed 343
      recurrences and 305 deaths (median follow-up: 7 years). Patients in the highest
      vs. lowest quartile of marine omega-3 PUFA intake had an HR for DFS of 0.72 (95%
      CI, 0.54-0.97; Ptrend = 0.03). Individuals who consumed dark fish >=1/week versus
      never had longer DFS (HR 0.65; 95% CI, 0.48-0.87; P-value = 0.007), RFS (HR 0.61;
      95% CI, 0.46-0.86; Ptrend = 0.007), and OS (HR 0.68; 95% CI, 0.48-0.96; Ptrend =
      0.04). In a subset of 510 patients, the association between marine omega-3 PUFA
      intake and DFS appeared stronger in patients with high PTGS2 expression (HR 0.32;
      95% CI, 0.11-0.95; Ptrend = 0.01) compared with patients with absent/low PTGS2
      expression (HR 0.78; 95% CI, 0.48-1.27; Ptrend = 0.35; Pinteraction =
      0.19).Conclusions: Patients with high intake of marine omega-3 PUFAs and dark
      fish after colon cancer diagnosis may have longer DFS.Impact: Randomized
      controlled trials examining dark fish and/or marine omega-3 PUFA supplements and
      colon cancer recurrence/survival are needed. Cancer Epidemiol Biomarkers Prev;
      27(4); 438-45. (c)2018 AACR.

PMID- 29358226
TI  - Cesarean Delivery and Risk of Infant Leukemia: A Report from the Children's
      Oncology Group.
AB  - Background: Studies have reported increased risks of pediatric acute
      lymphoblastic leukemia (ALL) among children born by cesarean delivery (CD).
      However, no previous study has examined the impact of CD on risk of infant
      leukemia specifically.Methods: In this study, 443 infants diagnosed with acute
      leukemia, including both ALL and acute myelogenous leukemia (AML), were
      identified at Children's Oncology Group institutions between January 1996 and
      December 2006; 324 controls frequency matched by year of birth were identified
      though random digit dialing and random selection from U.S. birth registries.
      Using interview data and, for a subset of participants, medical record data, we
      analyzed CD overall and by indications that likely resulted in pre-labor CD
      (PLCD) or emergency CD (ECD). Odds ratios (ORs) and 95% confidence intervals
      (CIs) for risk of ALL and AML were estimated using multivariable unconditional
      logistic regression models, adjusted for year of birth, birth weight, and
      maternal race.Results: We observed an increased point estimate for the
      association between CD and ALL (OR, 1.52 and 95% CI, 1.02-2.25). We did not
      observe an association between CD and AML (OR, 1.02 and 95% CI, 0.64-1.62). In
      analyses of indication for CD, we observed elevated effect estimates for the
      associations of both PLCD and ECD and infant ALL.Conclusions: Our analysis
      suggests an increased risk of infant ALL following CD, including both PLCD and
      ECD. Altered microbiota colonization may be involved in development of leukemia
      in infants, but clear biological mechanisms have yet to be determined.Impact:
      This study provides the first in-depth examination of CD and infant leukemia.
      Cancer Epidemiol Biomarkers Prev; 27(4); 473-8. (c)2018 AACR.

PMID- 29358225
TI  - Association between Post-Cancer Diagnosis Dietary Inflammatory Potential and
      Mortality among Invasive Breast Cancer Survivors in the Women's Health
      Initiative.
AB  - Background: Inflammation is important in chronic disease and can be modulated by
      dietary exposures. Our aim was to examine whether the inflammatory potential of
      diet after cancer diagnosis, assessed using the dietary inflammatory index (DII),
      is associated with all-cause and cause-specific mortality among women diagnosed
      with invasive breast cancer in the Women's Health Initiative (WHI).Methods: Our
      analytic cohort included 2,150 postmenopausal women, ages 50 to 79 years at
      baseline, who developed invasive breast cancer during follow-up and completed a
      food frequency questionnaire (FFQ) on average 1.5 years after diagnosis. Women
      were followed from breast cancer diagnosis until death or the end of follow-up by
      October 2014. Energy-adjusted DII (E-DII) scores were calculated from food plus
      supplements using a nutrient-density approach. Cox proportional hazards models
      were fit to estimate multivariable-adjusted HRs and 95% confidence intervals
      (CIs) for all-cause, breast cancer-specific, and cardiovascular disease (CVD)
      mortality.Results: After a median 13.3 years of follow-up, 580 deaths from any
      cause occurred, including 212 breast cancer deaths and 103 CVD deaths. Lower
      (i.e., more anti-inflammatory) E-DII scores were associated with a lower risk of
      CVD mortality (HRQ1VSQ4 = 0.44; 95% CI, 0.24-0.82; Ptrend = 0.005), but not with
      breast cancer-specific mortality (HRQ1VSQ4 = 0.96; 95% CI, 0.62-1.49; Ptrend =
      0.96) or all-cause mortality (HRQ1VSQ4 = 0.82; 95% CI, 0.63-1.05; Ptrend =
      0.17).Conclusions: Consuming a more anti-inflammatory diet after breast cancer
      diagnosis may be a means for reducing risk of death from CVD.Impact: Survival
      after invasive breast cancer diagnosis may be improved by consumption of an anti
      inflammatory diet. Cancer Epidemiol Biomarkers Prev; 27(4); 454-63. (c)2018 AACR.

PMID- 29358227
TI  - Inflammatory Pathways Regulated by Tumor Necrosis Receptor-Associated Factor 1
      Protect From Metabolic Consequences in Diet-Induced Obesity.
AB  - RATIONALE: The coincidence of inflammation and metabolic derangements in obese
      adipose tissue has sparked the concept of met-inflammation. Previous
      observations, however, suggest that inflammatory pathways may not ultimately
      cause dysmetabolism. OBJECTIVE: We have revisited the relationship between
      inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor
      associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF
      (tumor necrosis factor)-alpha, IL (interleukin)-1beta, and TLRs (toll-like
      receptors). METHODS AND RESULTS: Mice deficient for TRAF-1, which is expressed in
      obese adipocytes and adipose tissue lymphocytes, caused an expected
      hyperinflammatory phenotype in adipose tissue with enhanced adipokine and
      chemokine expression, increased leukocyte accumulation, and potentiated
      proinflammatory signaling in macrophages and adipocytes in a mouse model of diet
      induced obesity. Unexpectedly, TRAF-1-/- mice were protected from metabolic
      derangements and adipocyte growth, failed to gain weight, and showed improved
      insulin resistance-an effect caused by increased lipid breakdown in adipocytes
      and UCP (uncoupling protein)-1-enabled thermogenesis. TRAF-1-dependent catabolic
      and proinflammatory cues were synergistically driven by beta3-adrenergic and
      inflammatory signaling and required the presence of both TRAF-1-deficient
      adipocytes and macrophages. In human obesity, TRAF-1-dependent genes were
      upregulated. CONCLUSIONS: Enhancing TRAF-1-dependent inflammatory pathways in a
      gain-of-function approach protected from metabolic derangements in diet-induced
      obesity. These findings identify TRAF-1 as a regulator of dysmetabolism in mice
      and humans and question the pathogenic role of chronic inflammation in
      metabolism.

PMID- 29358228
TI  - E2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone
      Marrow Progenitor Cells.
AB  - RATIONALE: The majority of current cardiovascular cell therapy trials use bone
      marrow progenitor cells (BM PCs) and achieve only modest efficacy; the limited
      potential of these cells to differentiate into endothelial-lineage cells is one
      of the major barriers to the success of this promising therapy. We have
      previously reported that the E2F transcription factor 1 (E2F1) is a repressor of
      revascularization after ischemic injury. OBJECTIVE: We sought to define the role
      of E2F1 in the regulation of BM PC function. METHODS AND RESULTS: Ablation of
      E2F1 (E2F1 deficient) in mouse BM PCs increases oxidative metabolism and reduces
      lactate production, resulting in enhanced endothelial differentiation. The
      metabolic switch in E2F1-deficient BM PCs is mediated by a reduction in the
      expression of pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase kinase
      2; overexpression of pyruvate dehydrogenase kinase 4 reverses the enhancement of
      oxidative metabolism and endothelial differentiation. Deletion of E2F1 in the BM
      increases the amount of PC-derived endothelial cells in the ischemic myocardium,
      enhances vascular growth, reduces infarct size, and improves cardiac function
      after myocardial infarction. CONCLUSION: Our results suggest a novel mechanism by
      which E2F1 mediates the metabolic control of BM PC differentiation, and
      strategies that inhibit E2F1 or enhance oxidative metabolism in BM PCs may
      improve the effectiveness of cell therapy.

PMID- 29358229
TI  - Clonal Expansion of Endothelial Cells Contributes to Ischemia-Induced
      Neovascularization.
AB  - RATIONALE: Vascularization is critical to maintain organ function. Although many
      molecular pathways were shown to control vessel growth, the genuine process of
      capillary formation under different conditions is unclear. OBJECTIVE: Here, we
      elucidated whether clonal expansion contributes to vessel growth by using
      Confetti mice for genetic tracing of clonally expanding endothelial cells (ECs).
      METHODS AND RESULTS: In postnatal retina angiogenesis, we predominantly observed
      random distribution of fluorescence labeled ECs indicative of random integration
      or cell mixing. However, in models of pathophysiological angiogenesis
      (retinopathy of prematurity), as well as ischemia-induced angiogenesis in limbs
      and hearts, clonally expanded ECs were significantly more abundant (<=69%).
      Inhibition of VEGFR2 (vascular endothelial growth factor receptor 2) reduced
      clonal expansion after ischemia. To determine the mechanism underlying clonal
      expansion in vivo, we assessed gene expression specifically in clonally expanded
      ECs selected by laser capture microscopy. Clonally expanded ECs showed an
      enrichment of genes involved in endothelial-to-mesenchymal transition. Moreover,
      hypoxia-induced clonal expansion and endothelial-to-mesenchymal transition in ECs
      in vitro suggesting that hypoxia-enhanced endothelial-to-mesenchymal transition
      might contribute to vessel growth under ischemia. CONCLUSIONS: Our data suggest
      that neovascularization after ischemia is partially mediated by clonal expansion
      of ECs. Identification of the pathways that control clonal expansion may provide
      novel tools to augment therapeutic neovascularization or treat pathological
      angiogenesis.

PMID- 29358230
TI  - Carillion's toll on NHS.

PMID- 29358231
TI  - An Overexpressed Q Allele Leads to Increased Spike Density and Improved
      Processing Quality in Common Wheat (Triticum aestivum).
AB  - Spike density and processing quality are important traits in modern wheat
      production and are controlled by multiple gene loci. The associated genes have
      been intensively studied and new discoveries have been constantly reported during
      the past few decades. However, no gene playing a significant role in the
      development of these two traits has been identified. In the current study, a
      common wheat mutant with extremely compact spikes and good processing quality was
      isolated and characterized. A new allele (Qc1 ) of the Q gene (an important
      domestication gene) responsible for the mutant phenotype was cloned, and the
      molecular mechanism for the mutant phenotype was studied. Results revealed that
      Qc1 originated from a point mutation that interferes with the miRNA172-directed
      cleavage of Q transcripts, leading to its overexpression. It also reduces the
      longitudinal cell size of rachises, resulting in an increased spike density.
      Furthermore, Qc1 increases the number of vascular bundles, which suggests a
      higher efficiency in the transportation of assimilates in the spikes of the
      mutant than that of wild type. This accounts for the improved processing quality.
      The effects of Qc1 on spike density and wheat processing quality were confirmed
      by analyzing nine common wheat mutants possessing four different Qc alleles.
      These results deepen our understanding of the key roles of Q gene, and provide
      new insights for the potential application of Qc alleles in wheat quality
      breeding.

PMID- 29358232
TI  - Improving Genomic Prediction in Cassava Field Experiments by Accounting for
      Interplot Competition.
AB  - Plants competing for available resources is an unavoidable phenomenon in a field.
      We conducted studies in cassava (Manihot esculenta Crantz) in order to understand
      the pattern of this competition. Taking into account the competitive ability of
      genotypes while selecting parents for breeding advancement or commercialization
      can be very useful. We assumed that competition could occur at two levels: (i)
      the genotypic level, which we call interclonal, and (ii) the plot level
      irrespective of the type of genotype, which we call interplot competition or
      competition error. Modification in incidence matrices was applied in order to
      relate neighboring genotype/plot to the performance of a target genotype/plot
      with respect to its competitive ability. This was added into a genomic selection
      (GS) model to simultaneously predict the direct and competitive ability of a
      genotype. Predictability of the models was tested through a 10-fold cross
      validation method repeated five times. The best model was chosen as the one with
      the lowest prediction root mean squared error (pRMSE) compared to that of the
      base model having no competitive component. Results from our real data studies
      indicated that <10% increase in accuracy was achieved with GS-interclonal
      competition model, but this value reached up to 25% with a GS-competition error
      model. We also found that the competitive influence of a cassava clone is not
      just limited to the adjacent neighbors but spreads beyond them. Through
      simulations, we found that a 26% increase of accuracy in estimating trait
      genotypic effect can be achieved even in the presence of high competitive
      variance.

PMID- 29358233
TI  - The control of paramyxovirus genome hexamer length and mRNA editing.
AB  - The unusual ability of a human parainfluenza virus type 2 (hPIV2) nucleoprotein
      point mutation (NPQ202A) to strongly enhance minigenome replication was found to
      depend on the absence of a functional, internal element of the bipartite
      replication promoter (CRII). This point mutation allows relatively robust CRII
      minus minigenome replication in a CRII-independent manner, under conditions in
      which NPwt is essentially inactive. The nature of the amino acid at position 202
      apparently controls whether viral RNA-dependent RNA polymerase (vRdRp) can, or
      cannot, initiate RNA synthesis in a CRII-independent manner. By repressing genome
      synthesis when vRdRp cannot correctly interact with CRII, gln202 of N, the only
      residue of the RNA-binding groove that contacts a nucleotide base in the N-RNA,
      acts as a gatekeeper for wild-type (CRII-dependent) RNA synthesis. This ensures
      that only hexamer-length genomes are replicated, and that the critical hexamer
      phase of the cis-acting mRNA editing sequence is maintained.

PMID- 29358234
TI  - nextPARS: parallel probing of RNA structures in Illumina.
AB  - RNA molecules play important roles in virtually every cellular process. These
      functions are often mediated through the adoption of specific structures that
      enable RNAs to interact with other molecules. Thus, determining the secondary
      structures of RNAs is central to understanding their function and evolution. In
      recent years several sequencing-based approaches have been developed that allow
      probing structural features of thousands of RNA molecules present in a sample.
      Here, we describe nextPARS, a novel Illumina-based implementation of in vitro
      parallel probing of RNA structures. Our approach achieves comparable accuracy to
      previous implementations, while enabling higher throughput and sample
      multiplexing.

PMID- 29358235
TI  - Transcriptional and chromatin changes accompanying de novo formation of
      transgenic piRNA clusters.
AB  - Expression of transposable elements in the germline is controlled by Piwi
      interacting (pi) RNAs produced by genomic loci termed piRNA clusters and
      associated with Rhino, a heterochromatin protein 1 (HP1) homolog. Previously, we
      have shown that transgenes containing a fragment of the I retrotransposon form de
      novo piRNA clusters in the Drosophila germline providing suppression of I-element
      activity. We noted that identical transgenes located in different genomic sites
      vary considerably in piRNA production and classified them as "strong" and "weak"
      piRNA clusters. Here, we investigated what chromatin and transcriptional changes
      occur at the transgene insertion sites after their conversion into piRNA
      clusters. We found that the formation of a transgenic piRNA cluster is
      accompanied by activation of transcription from both genomic strands that likely
      initiates at multiple random sites. The chromatin of all transgene-associated
      piRNA clusters contain high levels of trimethylated lysine 9 of histone H3
      (H3K9me3) and HP1a, whereas Rhino binding is considerably higher at the strong
      clusters. None of these chromatin marks was revealed at the "empty" sites before
      transgene insertion. Finally, we have shown that in the nucleus of polyploid
      nurse cells, the formation of a piRNA cluster at a given transgenic genomic copy
      works according to an "all-or-nothing" model: either there is high Rhino
      enrichment or there is no association with Rhino at all. As a result, genomic
      copies of a weak piRNA transgenic cluster show a mosaic association with Rhino
      foci, while the majority of strong transgene copies associate with Rhino and are
      hence involved in piRNA production.

PMID- 29358236
TI  - We must support junior doctors working after hours.

PMID- 29358238
TI  - For the scholarly, free-thinking family physician.

PMID- 29358237
TI  - Stretching the arms of the type VI secretion sheath protein.

PMID- 29358239
TI  - ?

PMID- 29358240
TI  - Composition of Canadian Pain Society guideline development group?

PMID- 29358241
TI  - Estimating cancer risk from radiation.

PMID- 29358242
TI  - Correction.

PMID- 29358243
TI  - Patient perspectives: Exploring patient values and preferences.

PMID- 29358244
TI  - ?

PMID- 29358246
TI  - Eliciting patient values and preferences to inform shared decision making in
      preventive screening.

PMID- 29358247
TI  - When you suspect diabetes in a child.

PMID- 29358245
TI  - Deprescribing antipsychotics for behavioural and psychological symptoms of
      dementia and insomnia: Evidence-based clinical practice guideline.
AB  - OBJECTIVE: To develop an evidence-based guideline to help clinicians make
      decisions about when and how to safely taper and stop antipsychotics; to focus on
      the highest level of evidence available and seek input from primary care
      professionals in the guideline development, review, and endorsement processes.
      METHODS: The overall team comprised 9 clinicians (1 family physician, 1 family
      physician specializing in long-term care, 1 geriatric psychiatrist, 2
      geriatricians, 4 pharmacists) and a methodologist; members disclosed conflicts of
      interest. For guideline development, a systematic process was used, including the
      GRADE (Grading of Recommendations Assessment, Development and Evaluation)
      approach. Evidence was generated from a Cochrane systematic review of
      antipsychotic deprescribing trials for the behavioural and psychological symptoms
      of dementia, and a systematic review was conducted to assess the evidence behind
      the benefits of using antipsychotics for insomnia. A review of reviews of the
      harms of continued antipsychotic use was performed, as well as narrative
      syntheses of patient preferences and resource implications. This evidence and
      GRADE quality-of-evidence ratings were used to generate recommendations. The team
      refined guideline content and recommendation wording through consensus and
      synthesized clinical considerations to address common front-line clinician
      questions. The draft guideline was distributed to clinicians and stakeholders for
      review and revisions were made at each stage. RECOMMENDATIONS: We recommend
      deprescribing antipsychotics for adults with behavioural and psychological
      symptoms of dementia treated for at least 3 months (symptoms stabilized or no
      response to an adequate trial) and for adults with primary insomnia treated for
      any duration or secondary insomnia in which underlying comorbidities are managed.
      A decision-support algorithm was developed to accompany the guideline.
      CONCLUSION: Antipsychotics are associated with harms and can be safely tapered.
      Patients and caregivers might be more amenable to deprescribing if they
      understand the rationale (potential for harm), are involved in developing the
      tapering plan, and are offered behavioural advice or management. This guideline
      provides recommendations for making decisions about when and how to reduce the
      dose of or stop antipsychotics. Recommendations are meant to assist with, not
      dictate, decision making in conjunction with patients and families.

PMID- 29358248
TI  - Rare presentation of acute aortic dissection in a family doctor's office.

PMID- 29358249
TI  - Choosing Wisely Canada recommendations.

PMID- 29358250
TI  - Determining the causes of postural hypotension.

PMID- 29358251
TI  - Infant sleep training: rest easy?

PMID- 29358252
TI  - Can we eliminate HIV?

PMID- 29358253
TI  - Stubborn heel pain: Treatment of plantar fasciitis using high-load strength
      training.

PMID- 29358254
TI  - Screening with Papanicolaou tests in Alberta: Are we Choosing Wisely?
AB  - OBJECTIVE: To describe the prevalence and geographic distribution of cervical
      cancer screening, as well as the age groups of those undergoing screening, in
      Alberta, and to determine if screening practices conform to current guidelines
      and follow Choosing Wisely Canada recommendations. DESIGN: Descriptive study
      using data from the Alberta Ministry of Health Analytics and Performance
      Reporting Branch. SETTING: Alberta. PARTICIPANTS: Women who had 1 or more
      Papanicolaou tests between 2011 and 2013. MAIN OUTCOME MEASURES: Number of women
      aged 15 to 20 and those aged 70 and older who had 1 or more Pap tests in a 3-year
      period; year-to-year trends in screening rates for women in these 2 age groups;
      trends in screening rates in various geographic regions (ie, cities and zones) in
      Alberta; and the discipline of clinicians who ordered the Pap tests. RESULTS:
      Between 2011 and 2013, 805 632 women in the province of Alberta had 1 or more Pap
      tests for cervical cancer screening. Overall, 25 511 (17.5%) women aged 15 to 20
      and 16 818 (10.3%) aged 70 and older were screened contrary to most existing
      guidelines. Screening rates varied markedly in different geographic regions of
      the province. Most Pap tests were ordered by family physicians or general
      practitioners. CONCLUSION: Within the geographic regions of Alberta, provincial,
      national, and international guidelines for screening with Pap tests are
      inconsistently followed. This strongly echoes the need for clinicians and
      patients to consider the Choosing Wisely Canada recommendations and current
      guidelines for cervical cancer screening.

PMID- 29358255
TI  - Hope for Superman.

PMID- 29358257
TI  - Our power to negotiate with electronic medical record vendors.

PMID- 29358256
TI  - Housecalls: Essential art in family medicine.

PMID- 29358258
TI  - ?

PMID- 29358259
TI  - ?

PMID- 29358260
TI  - Technology, compassionate care, and family practice.

PMID- 29358261
TI  - ?

PMID- 29358262
TI  - ?

PMID- 29358263
TI  - ?

PMID- 29358264
TI  - ?

PMID- 29358265
TI  - Experiences of practice facilitators working on the Improved Delivery of
      Cardiovascular Care project: Retrospective case study.
AB  - OBJECTIVE: To examine the barriers to and facilitators of practice facilitation
      experienced by participants in the Improving Delivery of Cardiovascular Care
      (IDOCC) project. DESIGN: Case studies of practice facilitators' narrative
      reports. SETTING: Eastern Ontario. PARTICIPANTS: Primary care practices that
      participated in the IDOCC project. MAIN OUTCOME MEASURES: Cases were identified
      by calculating sum scores in order to determine practices' performance relative
      to their peers. Two case exemplars were selected that scored within +/- 1 SD of
      the total mean score, and a qualitative analysis of practice facilitators'
      narrative reports was conducted using a 5-factor implementation framework to
      identify barriers and facilitators. Narratives were divided into 3 phases:
      planning, implementation, and sustainability. RESULTS: Barriers and facilitators
      fluctuated over the intervention's 3 phases. Site A reported more barriers (n =
      47) than facilitators (n = 38), while site B reported a roughly equal number of
      barriers (n = 144) and facilitators (n = 136). In both sites, the most common
      barriers involved organizational and provider factors and the most common
      facilitators were associated with innovation and structural factors. CONCLUSION:
      Both practices encountered various barriers and facilitators throughout the
      IDOCC's 3 phases. The case studies reveal the complex interactions of these
      factors over time, and provide insight into the implementation of practice
      facilitation programs.

PMID- 29358267
TI  - Does clinical exposure matter? Pilot assessment of patient visits in an urban
      family medicine residency program.
AB  - OBJECTIVE: To determine the number of patient visits, patient demographic
      information, and diagnoses in an urban ambulatory care setting in a family
      medicine residency program, and assess the correlation between the number of
      patient visits and residents' in-training examination (ITE) scores. DESIGN:
      Retrospective analysis of data from resident practice profiles, electronic
      medical records, and residents' final ITE scores. SETTING: Family medicine
      teaching unit in a community hospital in Barrie, Ont. PARTICIPANTS: Practice
      profile data were from family medicine residents enrolled in the program from
      July 1, 2013, to June 30, 2014, and electronic medical record and ITE data were
      from those enrolled in the program from July 1, 2010, to June 30, 2015. MAIN
      OUTCOME MEASURES: Number of patient visits, patient characteristics (eg, sex,
      age), priority topics addressed in clinic, resident characteristics (eg, age,
      sex, level of residency), and residents' final ITE scores. RESULTS: Between July
      1, 2013, and June 30, 2014, there were 11 115 patient visits. First-year
      residents had a mean of 5.48 patient visits per clinic, and second-year residents
      had a mean of 5.98 patient visits per clinic. A Pearson correlation coefficient
      of 0.68 was found to exist between the number of patients seen and the final ITE
      scores, with a 10.5% difference in mean score between residents who had 1251 or
      more visits and those who had 1150 or fewer visits. Three diagnoses (ie,
      epistaxis, meningitis, and neck pain) deemed important for Certification by the
      College of Family Physicians of Canada were not seen by any of the residents in
      clinic. CONCLUSION: There is a moderate correlation between the number of
      patients seen by residents in ambulatory care and ITE scores in family medicine.
      It is important to assess patients' demographic information and diagnoses made in
      resident practices to ensure an adequate clinical experience.

PMID- 29358266
TI  - Associations between sensory loss and social networks, participation, support,
      and loneliness: Analysis of the Canadian Longitudinal Study on Aging.
AB  - OBJECTIVE: To determine if hearing loss, vision loss, and dual sensory loss were
      associated with social network diversity, social participation, availability of
      social support, and loneliness, respectively, in a population-based sample of
      older Canadians and to determine whether age or sex modified the associations.
      DESIGN: Cross-sectional population-based study. SETTING: Canada. PARTICIPANTS:
      The sample included 21 241 participants in the Canadian Longitudinal Study on
      Aging tracking cohort. The sample was nationally representative of English- and
      French-speaking, non-institutionalized 45- to 89-year-old Canadians who did not
      live on First Nations reserves and who had normal cognition. Participants with
      missing data for any of the variables in the multivariable regression models were
      excluded from analysis. MAIN OUTCOME MEASURES: Hearing and vision loss were
      determined by self-report. Dual sensory loss was defined as reporting both
      hearing and vision loss. Univariate analyses were performed to assess cross
      sectional associations between hearing, vision, and dual sensory loss, and
      social, demographic, and medical variables. Multivariable regression models were
      used to analyze cross-sectional associations between each type of sensory loss
      and social network diversity, social participation, availability of social
      support, and loneliness. RESULTS: Vision loss (in men) and dual sensory loss (in
      65- to 85-year-olds) were independently associated with reduced social network
      diversity. Vision loss and dual sensory loss (in 65- to 85-year-olds) were each
      independently associated with reduced social participation. All forms of sensory
      loss were associated with both low availability of social support and loneliness.
      CONCLUSION: Sensory impairment is associated with reduced social function in
      older Canadians. Interventions and research that address the social needs of
      older individuals with sensory loss are needed.

PMID- 29358268
TI  - ?

PMID- 29358269
TI  - ?

PMID- 29358270
TI  - High predictive value of brain MRI imaging in primary mitochondrial respiratory
      chain deficiency.
AB  - BACKGROUND: Because the mitochondrial respiratory chain (RC) is ubiquitous, its
      deficiency can theoretically give rise to any symptom in any organ or tissue at
      any age with any mode of inheritance, owing to the twofold genetic origin of
      respiratory enzyme machinery, that is, nuclear and mitochondrial. Not all
      respiratory enzyme deficiencies are primary and secondary or artefactual
      deficiency is frequently observed, leading to a number of misleading conclusions
      and inappropriate investigations in clinical practice. This study is aimed at
      investigating the potential role of brain MRI in distinguishing primary RC
      deficiency from phenocopies and other aetiologies. METHODS: Starting from a large
      series of 189 patients (median age: 3.5 years (8 days-56 years), 58% males)
      showing signs of RC enzyme deficiency, for whom both brain MRIs and disease
      causing mutations were available, we retrospectively studied the positive
      predictive value (PPV) and the positive likelihood ratio (LR+) of brain MRI
      imaging and its ability to discriminate between two groups: primary deficiency of
      the mitochondrial RC machinery and phenocopies. RESULTS: Detection of (1)
      brainstem hyperintensity with basal ganglia involvement (P<=0.001) and (2)
      lactate peak with either brainstem or basal ganglia hyperintensity was highly
      suggestive of primary RC deficiency (P<=0.01). Fourteen items had a PPV>95% and
      LR+ was greater than 9 for seven signs. Biallelic SLC19A3 mutations represented
      the main differential diagnosis. Non-significant differences between the two
      groups were found for cortical/subcortical atrophy, leucoencephalopathy and
      involvement of caudate nuclei, spinothalamic tract and corpus callosum.
      CONCLUSION: Based on these results and owing to invasiveness of skeletal muscle
      biopsies and cost of high-throughput DNA sequencing, we suggest giving
      consideration to brain MRI imaging as a diagnostic marker and an informative
      investigation to be performed in patients showing signs of RC enzyme deficiency.

PMID- 29358271
TI  - Catalogue of inherited disorders found among the Irish Traveller population.
AB  - Background Irish Travellers are an endogamous, nomadic, ethnic minority
      population mostly resident on the island of Ireland with smaller populations in
      Europe and the USA. High levels of consanguinity result in many rare autosomal
      recessive disorders. Due to founder effects and endogamy, most recessive
      disorders are caused by specific homozygous mutations unique to this population.
      Key clinicians and scientists with experience in managing rare disorders seen in
      this population have developed a de facto advisory service on differential
      diagnoses to consider when faced with specific clinical scenarios. Objective(s)
      To catalogue all known inherited disorders found in the Irish Traveller
      population. Methods We performed detailed literature and database searches to
      identify relevant publications and the disease mutations of known genetic
      disorders found in Irish Travellers. Results We identified 104 genetic disorders:
      90 inherited in an autosomal recessive manner; 13 autosomal dominant and one a
      recurring chromosomal duplication. Conclusion We have collated our experience of
      inherited disorders found in the Irish Traveller population to make it publically
      available through this publication to facilitate a targeted genetic approach to
      diagnostics in this ethnic group.

PMID- 29358272
TI  - FAM46A mutations are responsible for autosomal recessive osteogenesis imperfecta.
AB  - BACKGROUND: Stuve-Wiedemann syndrome (SWS) is characterised by bowing of the
      lower limbs, respiratory distress and hyperthermia that are often responsible for
      early death. Survivors develop progressive scoliosis and spontaneous fractures.
      We previously identified LIFR mutations in most SWS cases, but absence of LIFR
      pathogenic changes in five patients led us to perform exome sequencing and to
      identify homozygosity for a FAM46A mutation in one case [p.Ser205Tyrfs*13]. The
      follow-up of this case supported a final diagnosis of osteogenesis imperfecta
      (OI), based on vertebral collapses and blue sclerae. METHODS AND RESULTS: This
      prompted us to screen FAM46A in 25 OI patients with no known mutations.We
      identified a homozygous deleterious variant in FAM46A in two affected sibs with
      typical OI [p.His127Arg]. Another homozygous variant, [p.Asp231Gly], also classed
      as deleterious, was detected in a patient with type III OI of consanguineous
      parents using homozygosity mapping and exome sequencing.FAM46A is a member of the
      superfamily of nucleotidyltransferase fold proteins but its exact function is
      presently unknown. Nevertheless, there are lines of evidence pointing to a
      relevant role of FAM46A in bone development. By RT-PCR analysis, we detected
      specific expression of FAM46A in human osteoblasts andinterestingly, a nonsense
      mutation in Fam46a has been recently identified in an ENU-derived (N-ethyl-N
      nitrosourea) mouse model characterised by decreased body length, limb, rib,
      pelvis, and skull deformities and reduced cortical thickness in long bones.
      CONCLUSION: We conclude that FAM46A mutations are responsible for a severe form
      of OI with congenital bowing of the lower limbs and suggest screening this gene
      in unexplained OI forms.

PMID- 29358273
TI  - cIAP1/2-TRAF2-SHP-1-Src-MyD88 Complex Regulates Lipopolysaccharide-Induced IL-27
      Production through NF-kappaB Activation in Human Macrophages.
AB  - The inhibitors of apoptosis (IAP) proteins, initially described in the context of
      apoptosis regulation as promoting cell survival, have recently emerged as key
      regulators of innate immune signaling. As a result, downregulation of IAP via
      Smac mimetics (SMM) has both survival and immunoregulatory effects. IAPs modulate
      cytokine production in murine models either as a single agent or in response to
      LPS. However, the role of SMM and the involvement of IAPs in primary human cells
      and in particular macrophages with respect to cytokine production and innate
      immune responses remain largely unknown. IL-27, a member of the IL-12 cytokine
      family produced by APCs such as macrophages, has broad immunoregulatory
      properties in both innate and adaptive immune responses. Herein, we show that
      cellular IAPs (cIAPs) positively regulate LPS-induced IL-27 production in both
      primary human monocytes and macrophages. Investigations for the signaling
      mechanism of cIAPs involvement in IL-27 production in human macrophages revealed
      that LPS-induced IL-27 production is regulated by a novel signaling complex
      comprising cIAP1/2, TNFR-associated factor 2 (TRAF2), SHP-1, Src, and MyD88
      leading to p38, c-Jun N-terminal kinases (JNK) and Akt activation and NF-kappaB
      signaling. In cancer cells, SMM induce the production of cytokines by activating
      the noncanonical alternate NF-kappaB pathway. However, in human macrophages, SMM
      do not induce the production of TNF-alpha and other cytokines while inhibiting
      LPS-induced IL-27 production by inhibiting the classical NF-kappaB pathway. These
      signaling pathways may constitute novel therapeutic avenues for immune modulation
      of IL-27 and provide insight into the modulatory immune effects of SMM.

PMID- 29358274
TI  - CD8alpha+CD11c+ Extracellular Vesicles in the Lungs Control Immune Homeostasis of
      the Respiratory Tract via TGF-beta1 and IL-10.
AB  - The immune balance of the respiratory tract is strictly regulated. Extracellular
      vesicles (EVs) have been reported to participate in maintaining the immune
      balance in the intestinal tract, but whether they are involved in regulation of
      the immune balance in the respiratory tract has yet to be revealed. In this
      study, we found that physiological EVs from lungs of WT mice (L-EVs) could be
      isolated, which contained the immunosuppressive cytokines TGF-beta1 and IL-10.
      Among L-EV subsets, only the CD8alpha+CD11c+ EV subset was positive for TGF-beta1
      and IL-10 and could inhibit CD4+ T cell proliferation via TGF-beta1 in vitro and
      relieve murine asthmatic symptoms. Mechanistically, L-EVs were effective at
      inhibiting OVA peptide-specific CD4+ T cell proliferation in a TGF-beta1- and IL
      10-dependent manner. In addition, they could prevent CD4+ T cells from hilar
      lymph nodes from secreting IL-4, IL-9, and IL-17A via IL-10 ex vivo, suggesting
      inhibition of Th2, Th9, and Th17 cell responses. Altogether, our results indicate
      that EVs from the lungs are involved in control of the immune balance in the
      respiratory tract, which reveals a novel mechanism in the maintenance of
      respiratory tract immune homeostasis.

PMID- 29358275
TI  - Erythrocyte Saturation with IgG Is Required for Inducing Antibody-Mediated Immune
      Suppression and Impacts Both Erythrocyte Clearance and Antigen-Modulation
      Mechanisms.
AB  - Anti-D prevents hemolytic disease of the fetus and newborn, and this mechanism
      has been referred to as Ab-mediated immune suppression (AMIS). Anti-D, as well as
      other polyclonal AMIS-inducing Abs, most often induce both epitope masking and
      erythrocyte clearance mechanisms. We have previously observed that some Abs that
      successfully induce AMIS effects could be split into those that mediate epitope
      masking versus those that induce erythrocyte clearance, allowing the ability to
      analyze these mechanisms separately. In addition, AMIS-inducing activity has
      recently been shown to induce Ag modulation (Ag loss from the erythrocyte
      surface). To assess these mechanisms, we immunized mice with transgenic murine
      RBCs expressing a single Ag protein comprising a recombinant Ag composed of hen
      egg lysozyme, OVA sequences comprising aa 251-349, and the human Duffy
      transmembrane protein (HOD-Ag) with serial doses of polyclonal anti-OVA IgG as
      the AMIS-inducing Ab. The anti-OVA Ab induced AMIS in the absence of apparent
      epitope masking. AMIS occurred only when the erythrocytes appeared saturated with
      IgG. This Ab was capable of inducing HOD-RBC clearance, as well as loss of the
      OVA epitope at doses of Ab that caused AMIS effects. HOD-RBCs also lost
      reactivity with Abs specific for the hen egg lysozyme and Duffy portions of the
      Ag consistent with the initiation of Ag modulation and/or trogocytosis
      mechanisms. These data support the concept that an AMIS-inducing Ab that does not
      cause epitope masking can induce AMIS effects in a manner consistent with RBC
      clearance and/or Ag modulation.

PMID- 29358276
TI  - Correction: Virtual Sorting Has a Distinctive Advantage in Identification of
      Anticorrelated Genes and Further Negative Regulators of Immune Cell
      Subpopulations.

PMID- 29358277
TI  - Intracellular BH3 Profiling Reveals Shifts in Antiapoptotic Dependency in Human B
      Cell Maturation and Mitogen-Stimulated Proliferation.
AB  - Apoptosis is critical to B cell maturation, but studies of apoptotic regulation
      in primary human B cells is lacking. In this study, we sought to better
      understand the mechanisms of apoptotic regulation in normal and activated B
      cells. Using intracellular BH3 profiling, we defined the Bcl2 dependency of B
      cell subsets from human peripheral blood and tonsillar lymphoid tissue as well as
      mitogen-activated B cells. We found that naive and memory B cells were BCL-2
      dependent, whereas germinal center B cells were MCL-1-dependent and plasma cells
      were BCL-XL-dependent. B cells stimulated to proliferate ex vivo by CpG or
      CD40L/IL-4 became more dependent on MCL-1 and BCL-XL As B cell lymphomas often
      rely on survival mechanisms derived from normal and activated B cells, these
      findings offer new insight into potential therapeutic strategies for lymphomas.

PMID- 29358278
TI  - Human and Rhesus Macaque KIR Haplotypes Defined by Their Transcriptomes.
AB  - The killer-cell Ig-like receptors (KIRs) play a central role in the immune
      recognition in infection, pregnancy, and transplantation through their
      interactions with MHC class I molecules. KIR genes display abundant copy number
      variation as well as high levels of polymorphism. As a result, it is challenging
      to characterize this structurally dynamic region. KIR haplotypes have been
      analyzed in different species using conventional characterization methods, such
      as Sanger sequencing and Roche/454 pyrosequencing. However, these methods are
      time-consuming and often failed to define complete haplotypes, or do not reach
      allele-level resolution. In addition, most analyses were performed on genomic
      DNA, and thus were lacking substantial information about transcription and its
      corresponding modifications. In this paper, we present a single-molecule real
      time sequencing approach, using Pacific Biosciences Sequel platform to
      characterize the KIR transcriptomes in human and rhesus macaque (Macaca mulatta)
      families. This high-resolution approach allowed the identification of novel Mamu
      KIR alleles, the extension of reported allele sequences, and the determination of
      human and macaque KIR haplotypes. In addition, multiple recombinant KIR genes
      were discovered, all located on contracted haplotypes, which were likely the
      result of chromosomal rearrangements. The relatively high number of contracted
      haplotypes discovered might be indicative of selection on small KIR repertoires
      and/or novel fusion gene products. This next-generation method provides an
      improved high-resolution characterization of the KIR cluster in humans and
      macaques, which eventually may aid in a better understanding and interpretation
      of KIR allele-associated diseases, as well as the immune response in
      transplantation and reproduction.

PMID- 29358279
TI  - Copper Regulates the Canonical NLRP3 Inflammasome.
AB  - Inflammasomes are multimeric protein complexes that are activated through a NOD
      like receptor and regulate the proteolytic activation of caspase-1 and cytokines,
      like IL-1beta. The NLRP3 inflammasome is implicated in many human pathologies
      including infections, autoinflammatory syndromes, chronic inflammation, and
      metabolic diseases; however, the molecular mechanisms of activation are not fully
      understood. In this study we show that NLRP3 inflammasome activation requires
      intracellular copper. A clinically approved copper chelator, tetrathiomolybdate,
      inhibited the canonical NLRP3 but not the AIM2, NLRC4, and NLRP1 inflammasomes or
      NF-kappaB-dependent priming. We demonstrate that NLRP3 inflammasome activation is
      blocked by removing copper from the active site of superoxide dismutase 1,
      recapitulating impaired inflammasome function in superoxide dismutase 1-deficient
      mice. This regulation is specific to macrophages, but not monocytes, both in mice
      and humans. In vivo, depletion of bioavailable copper resulted in attenuated
      caspase-1-dependent inflammation and reduced susceptibility to LPS-induced
      endotoxic shock. Our results indicate that targeting the intracellular copper
      homeostasis has potential for the treatment of NLRP3-dependent diseases.

PMID- 29358281
TI  - Visualising the interaction of CD4 T cells and DCs in the evolution of
      inflammatory arthritis.
AB  - OBJECTIVES: Successful early intervention in rheumatoid arthritis (RA) with the
      aim of resetting immunological tolerance requires a clearer understanding of how
      specificity, cellular kinetics and spatial behaviour shape the evolution of
      articular T cell responses. We aimed to define initial seeding of articular CD4+
      T cell responses in early experimental arthritis, evaluating their dynamic
      behaviour and interactions with dendritic cells (DCs) in the inflamed articular
      environment. METHODS: Antigen-induced arthritis was used to model articular
      inflammation. Flow cytometry and PCR of T cell receptor (TCR) diversity genes
      allowed phenotypic analysis of infiltrating T cells. The dynamic interactions of
      T cells with joint residing DCs were visualised using intravital multiphoton
      microscopy. RESULTS: Initial recruitment of antigen-specific T cells into the
      joint was paralleled by accumulation of CD4+ T cells with diverse antigen
      receptor expression and ability to produce tumour necrosis factor alpha
      (TNFalpha) and interferon gamma (IFNgamma) on mitogenic restimulation. A
      proportion of this infiltrate demonstrated slower motility speeds and engaged for
      longer periods with articular DCs in vivo. Abatacept treatment did not disrupt
      these interactions but did reduce T cell expression of inducible costimulatory
      (ICOS) molecule. We also demonstrated that non-specific CD4+ T cells could be
      recruited during these early articular events. CONCLUSIONS: We demonstrate that
      CD4+ T cells engage with articular DCs supporting antigen specific T cell
      reactivation. This cellular dialogue can be targeted therapeutically to reduce
      local T cell activation.

PMID- 29358282
TI  - Response to: 'Smoking paradox in the development of psoriatic arthritis among
      patients with psoriasis' by Lee and Song.

PMID- 29358280
TI  - Cytokine- and TCR-Mediated Regulation of T Cell Expression of Ly6C and Sca-1.
AB  - Ly6C and Sca-1 (Ly6A/E) are Ly6 family GPI-anchored surface molecules that are
      differentially expressed by multiple immune populations. Ly6C expression has been
      used to distinguish short-lived effector CD4+ T cells from memory precursor
      effector cells, whereas Sca-1 has been used in the identification of CD8+ memory
      stem cells. This study examines the expression patterns of these molecules and
      establishes that, in vitro, IL-27, type I IFN, and IFN-gamma are potent inducers
      of Ly6C and Sca-1 in naive mouse CD4+ and CD8+ T cells, whereas TGF-beta limits
      their expression. The induction of Ly6C and Sca-1 by IL-27 and IFN-gamma is
      dependent on STAT1, but not STAT3 or T-bet. In mouse splenocytes, at homeostasis,
      Ly6C and Sca-1 expression was not restricted to effector cells, but was also
      found at various levels on naive and memory populations. However, in response to
      infection with Toxoplasma gondii, pathogen-specific T cells expressed high levels
      of these molecules and in this context, endogenous IL-27 and IFN-gamma were
      required for the expression of Ly6C but not Sca-1. Together, these findings
      highlight the TCR-dependent and cytokine-mediated signals that modulate T cell
      expression of Ly6C and Sca-1 in vitro and in vivo during infection.

PMID- 29358283
TI  - Response to: 'Statins in systemic lupus erythematosus' by Abud-Mendoza.

PMID- 29358284
TI  - Response to: 'Depression and anxiety associate with less remission after 1 year
      in rheumatoid arthritis' by Boer et al.

PMID- 29358285
TI  - EULAR recommendations for the use of imaging in large vessel vasculitis in
      clinical practice.
AB  - To develop evidence-based recommendations for the use of imaging modalities in
      primary large vessel vasculitis (LVV) including giant cell arteritis (GCA) and
      Takayasu arteritis (TAK). European League Against Rheumatism (EULAR) standardised
      operating procedures were followed. A systematic literature review was conducted
      to retrieve data on the role of imaging modalities including ultrasound, MRI, CT
      and [18F]-fluorodeoxyglucose positron emission tomography (PET) in LVV. Based on
      evidence and expert opinion, the task force consisting of 20 physicians,
      healthcare professionals and patients from 10 EULAR countries developed
      recommendations, with consensus obtained through voting. The final level of
      agreement was voted anonymously. A total of 12 recommendations have been
      formulated. The task force recommends an early imaging test in patients with
      suspected LVV, with ultrasound and MRI being the first choices in GCA and TAK,
      respectively. CT or PET may be used alternatively. In case the diagnosis is still
      in question after clinical examination and imaging, additional investigations
      including temporal artery biopsy and/or additional imaging are required. In
      patients with a suspected flare, imaging might help to better assess disease
      activity. The frequency and choice of imaging modalities for long-term monitoring
      of structural damage remains an individual decision; close monitoring for aortic
      aneurysms should be conducted in patients at risk for this complication. All
      imaging should be performed by a trained specialist using appropriate operational
      procedures and settings. These are the first EULAR recommendations providing up
      to-date guidance for the role of imaging in the diagnosis and monitoring of
      patients with (suspected) LVV.

PMID- 29358287
TI  - Using Yeast Synthetic Lethality To Inform Drug Combination for Malaria.
AB  - Combinatorial chemotherapy is necessary for the treatment of malaria. However,
      finding a suitable partner drug for a new candidate is challenging. Here we
      develop an algorithm that identifies all of the gene pairs of Plasmodium
      falciparum that possess orthologues in yeast that have a synthetic lethal
      interaction but are absent in humans. This suggests new options for drug
      combinations, particularly for inhibitors of targets such as P. falciparum
      calcineurin, cation ATPase 4, or phosphatidylinositol 4-kinase.

PMID- 29358286
TI  - Aberrant tRNA processing causes an autoinflammatory syndrome responsive to TNF
      inhibitors.
AB  - OBJECTIVES: To characterise the clinical features, immune manifestations and
      molecular mechanisms in a recently described autoinflammatory disease caused by
      mutations in TRNT1, a tRNA processing enzyme, and to explore the use of cytokine
      inhibitors in suppressing the inflammatory phenotype. METHODS: We studied nine
      patients with biallelic mutations in TRNT1 and the syndrome of congenital
      sideroblastic anaemia with immunodeficiency, fevers and developmental delay
      (SIFD). Genetic studies included whole exome sequencing (WES) and candidate gene
      screening. Patients' primary cells were used for deep RNA and tRNA sequencing,
      cytokine profiling, immunophenotyping, immunoblotting and electron microscopy
      (EM). RESULTS: We identified eight mutations in these nine patients, three of
      which have not been previously associated with SIFD. Three patients died in early
      childhood. Inflammatory cytokines, mainly interleukin (IL)-6, interferon gamma
      (IFN-gamma) and IFN-induced cytokines were elevated in the serum, whereas tumour
      necrosis factor (TNF) and IL-1beta were present in tissue biopsies of patients
      with active inflammatory disease. Deep tRNA sequencing of patients' fibroblasts
      showed significant deficiency of mature cytosolic tRNAs. EM of bone marrow and
      skin biopsy samples revealed striking abnormalities across all cell types and a
      mix of necrotic and normal-appearing cells. By immunoprecipitation, we found
      evidence for dysregulation in protein clearance pathways. In 4/4 patients,
      treatment with a TNF inhibitor suppressed inflammation, reduced the need for
      blood transfusions and improved growth. CONCLUSIONS: Mutations of TRNT1 lead to a
      severe and often fatal syndrome, linking protein homeostasis and
      autoinflammation. Molecular diagnosis in early life will be crucial for
      initiating anti-TNF therapy, which might prevent some of the severe disease
      consequences.

PMID- 29358288
TI  - FKS2 and FKS3 Genes of Opportunistic Human Pathogen Candida albicans Influence
      Echinocandin Susceptibility.
AB  - Candida albicans, a prevailing opportunistic fungal pathogen of humans, has a
      diploid genome containing three homologous FKS genes that are evolutionarily
      conserved. One of these, the essential gene FKS1, encodes the catalytic subunit
      of glucan synthase, which is the target of echinocandin drugs and also serves as
      a site of drug resistance. The other two glucan synthase-encoding genes, FKS2 and
      FKS3, are also expressed, but their roles in resistance are considered
      unimportant. However, we report here that expression of FKS1 is upregulated in
      strains lacking either FKS2 or FKS3 Furthermore, in contrast to what is observed
      in heterozygous FKS1 deletion strains, cells lacking FKS2 or FKS3 contain
      increased amounts of cell wall glucan, are more resistant to echinocandin drugs,
      and consistently are tolerant to cell wall-damaging agents. Our data indicate
      that C. albicansFKS2 and FKS3 can act as negative regulators of FKS1, thereby
      influencing echinocandin susceptibility.

PMID- 29358289
TI  - Tn6450, a Novel Multidrug Resistance Transposon Characterized in a Proteus
      mirabilis Isolate from Chicken in China.
AB  - A novel 65.8-kb multidrug resistance transposon, designated Tn6450, was
      characterized in a Proteus mirabilis isolate from chicken in China. Tn6450
      contains 18 different antimicrobial resistance genes, including cephalosporinase
      gene blaDHA-1 and fluoroquinolone resistance genes qnrA1 and aac(6')-Ib-cr It
      carries a class 1/2 hybrid integron composed of intI2 and a 3' conserved segment
      of the class 1 integron. Tn6450 is derived from Tn7 via acquisition of new mobile
      elements and resistance genes.

PMID- 29358290
TI  - Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour
      Area under the Concentration-Time Curve in Neonates.
AB  - Bacterial sepsis is a major cause of morbidity and mortality in neonates,
      especially those involving methicillin-resistant Staphylococcus aureus (MRSA).
      Guidelines by the Infectious Diseases Society of America recommend the vancomycin
      24-h area under the concentration-time curve to MIC ratio (AUC24/MIC) of >400 as
      the best predictor of successful treatment against MRSA infections when the MIC
      is <=1 mg/liter. The relationship between steady-state vancomycin trough
      concentrations and AUC24 values (mg.h/liter) has not been studied in an Asian
      neonatal population. We conducted a retrospective chart review in Singapore
      hospitals and collected patient characteristics and therapeutic drug monitoring
      data from neonates on vancomycin therapy over a 5-year period. A one-compartment
      population pharmacokinetic model was built from the collected data, internally
      validated, and then used to assess the relationship between steady-state trough
      concentrations and AUC24 A Monte Carlo simulation sensitivity analysis was also
      conducted. A total of 76 neonates with 429 vancomycin concentrations were
      included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks)
      for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the
      initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and
      serum creatinine. For MRSA isolates with a vancomycin MIC of <=1, our major
      finding was that the minimum steady-state trough concentration range predictive
      of achieving an AUC24/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs
      within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC24/MIC of
      >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.

PMID- 29358291
TI  - Population Pharmacokinetics of High-Dose Tigecycline in Patients with Sepsis or
      Septic Shock.
AB  - Tigecycline is a glycylcycline often used in critically ill patients as the
      antibiotic of last resort. The pharmacokinetics (PK) of tigecycline in intensive
      care unit (ICU) patients can be affected by severe pathophysiological changes so
      that standard dosing might not be adequate. The aim of this study was to describe
      population PK of high-dose tigecycline in patients with sepsis or septic shock
      and evaluate the relationship between individual PK parameters and patient
      covariates. The study population consisted of 37 adult ICU patients receiving a
      200-mg loading dose of tigecycline followed by multiple doses of 100 mg every 12
      h. Blood samples were collected at 0.5, 2, 4, 8, and 12 h after dose
      administration. A two-compartment model with interindividual (IIV) and
      interoccasion (IOV) variability in PK parameters was used to describe the
      concentration-time course of tigecycline. The estimated values of mean population
      PK parameters were 22.1 liters/h and 69.4 liters/h for elimination and
      intercompartmental clearance, respectively, and 162 liters and 87.9 liters for
      volume of the central and peripheral compartment, respectively. The IIV and IOV
      in clearance were less than 20%. The estimated values of distribution volumes
      were different from previously published values, which might be due to
      pathophysiological changes in ICU patients. No systematic relationship between
      individual PK parameters and patient covariates was found. The developed model
      does not show evidence that individual tigecycline dosing adjustment based on
      patient covariates is necessary to obtain the same target concentration in
      patients with sepsis or septic shock. Dosing adjustments should be based on the
      pathogens, their susceptibility, and PK targets.

PMID- 29358292
TI  - Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin
      Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis
      from the Phase 3 SOLO Studies.
AB  - Oritavancin is a lipoglycopeptide with bactericidal activity against Gram
      positive organisms. Its rapid concentration-dependent bactericidal activity and
      long elimination half-life allow single-dose treatment of acute bacterial skin
      and skin structure infections (ABSSSI). SOLO I and SOLO II were randomized,
      double-blind studies evaluating the efficacy and safety of a single 1,200-mg
      intravenous (i.v.) dose of oritavancin versus twice-daily i.v. vancomycin for 7
      to 10 days in ABSSSI patients. Safety data from both studies were pooled for
      safety analysis. The database comprised pooled safety data for 976 oritavancin
      treated patients and 983 vancomycin-treated patients. The incidences of adverse
      events, serious adverse events, and discontinuations due to adverse events were
      similar for oritavancin (55.3, 5.8, and 3.7%, respectively) and vancomycin (56.9,
      5.9, and 4.2%, respectively). The median time to onset (3.8 days versus 3.1 days,
      respectively) and the duration (3.0 days for both groups) of adverse events were
      also similar between the two groups. The most frequently reported events were
      nausea, headache, and vomiting. Greater than 90% of all events were mild or
      moderate in severity. There were slightly more infections and infestations,
      abscesses or cellulitis, and hepatic and cardiac adverse events in the
      oritavancin group; however, more than 80% of these events were mild or moderate.
      Subgroup analyses did not identify clinically meaningful differences in the
      incidence of adverse events attributed to oritavancin. A single 1,200-mg dose of
      oritavancin was well tolerated and had a safety profile similar to that of twice
      daily vancomycin. The long elimination half-life of oritavancin compared to that
      of vancomycin did not result in a clinically meaningful delay to the onset or
      prolongation of adverse events. (This study has been registered at
      ClinicalTrials.gov under registration no. NCT01252719 and NCT01252732.).

PMID- 29358293
TI  - Amikacin Pharmacokinetic-Pharmacodynamic Analysis in Pediatric Cancer Patients.
AB  - We performed pharmacokinetic-pharmacodynamic (PK-PD) and simulation analyses to
      evaluate a standard amikacin dose of 15 mg/kg once daily in children with cancer
      and to determine an optimal dosing strategy. A population pharmacokinetic model
      was developed from clinical data collected in 34 pediatric patients and used in a
      simulation study to predict the population probability of various dosing regimens
      to achieve accepted safety (steady-state unbound trough plasma concentration
      [fCmin] of <10 mg/liter)- and efficacy (free, unbound plasma concentration-to-MIC
      ratio [fCmax/MIC] of >=8)-linked targets. In addition, an adaptive resistance PD
      (ARPD) model of Pseudomonas aeruginosa was built based on literature time-kill
      curve data and linked to the PK model to perform PK-ARPD simulations and compare
      results with those of the probability approach. Using the probability approach,
      an amikacin dose of 60 mg/kg administered once daily is expected to achieve the
      target fCmax/MIC in 80% of pediatric patients weighing 8 to 70 kg with a 97.5%
      probability, and almost all patients were predicted to have fCmin of <10
      mg/liter. However, PK-ARPD simulation predicted that 60 mg/kg/day is unlikely to
      suppress bacterial resistance with repeated dosing. Furthermore, PK-ARPD
      simulation suggested that amikacin at 90 mg/kg, given in two divided doses (45
      mg/kg twice a day), is expected to hit safety and efficacy targets and is
      associated with a lower rate of bacterial resistance. The disagreement between
      the two methods is due to the inability of the probability approach to predict
      development of drug resistance with repeated dosing. This originates from the use
      of PK-PD indices based on the MIC that neglects measurement errors, ignores the
      time course dynamic nature of bacterial growth and killing, and incorrectly
      assumes the MIC to be constant during treatment.

PMID- 29358294
TI  - Quantitative Analysis of Gentamicin Exposure in Neonates and Infants Calls into
      Question Its Current Dosing Recommendations.
AB  - Optimal dosing of gentamicin in neonates is still a matter of debate despite its
      common use. We identified gentamicin dosing regimens from eight international
      guidelines and seven Swiss neonatal intensive care units. The dose per
      administration, the dosing interval, the total daily dose, and the demographic
      characteristics between guidelines were compared. There was considerable
      variability with respect to dose (4 to 6 mg/kg), dosing interval (24 h to 48 h),
      total daily dose (2.5 to 6 mg/kg/day), and patient demographic characteristics
      that were used to calculate individualized dosing regimens. A model-based
      simulation study in 1071 neonates was performed to determine the achievement of
      efficacious peak gentamicin concentrations according to predefined MICs (Cmax/MIC
      >= 10) and safe trough concentrations (Cmin <= 2 mg/liter) with recommended
      dosing regimens. MIC targets of 0.5 and 1 mg/liter were used. Dosing optimization
      was performed giving priority to the first day of treatment and with the goal of
      simplifying dosing. Current gentamicin neonatal guidelines allow to achieve
      effective peak concentrations for MICs <= 0.5 mg/liter but not higher. Model
      based simulations indicate that to attain peak gentamicin concentrations of >=10
      mg/liter, a dose of 7.5 mg/kg should be administered using an extended dosing
      interval regimen. Trough concentrations of <=2 mg/liter can be maintained with a
      dosing interval of 36 to 48 h in neonates according to gestational and postnatal
      age. For treatment beyond 3 days, therapeutic drug monitoring is advised to
      maintain adequate serum concentrations.

PMID- 29358295
TI  - Orientia tsutsugamushi Is Highly Susceptible to the RNA Polymerase Switch Region
      Inhibitor Corallopyronin A In Vitro and In Vivo.
AB  - Scrub typhus is a potentially lethal infection caused by the obligate
      intracellular bacterium Orientia tsutsugamushi Reports on the emergence of
      doxycycline-resistant strains highlight the urgent need to develop novel
      antiinfectives against scrub typhus. Corallopyronin A (CorA) is a novel alpha
      pyrone compound synthesized by the myxobacterium Corallococcus coralloides that
      was characterized as a noncompetitive inhibitor of the switch region of the
      bacterial RNA polymerase (RNAP). We investigated the antimicrobial action of CorA
      against the human-pathogenic Karp strain of O. tsutsugamushiin vitro and in vivo
      The MIC of CorA against O. tsutsugamushi was remarkably low (0.0078 MUg/ml), 16
      fold lower than that against Rickettsia typhi In the lethal intraperitoneal O.
      tsutsugamushi mouse infection model, a minimum daily dose of 100 MUg CorA
      protected 100% of infected mice. Two days of treatment were sufficient to confer
      protection. In contrast to BALB/c mice, SCID mice succumbed to the infection
      despite treatment with CorA or tetracycline, suggesting that antimicrobial
      treatment required synergistic action of the adaptive immune response. Similar to
      tetracycline, CorA did not prevent latent infection of O. tsutsugamushiin vivo
      However, latency was not caused by acquisition of antimicrobial resistance, since
      O. tsutsugamushi reisolated from latently infected BALB/c mice remained fully
      susceptible to CorA. No mutations were found in the CorA-binding regions of the
      beta and beta' RNAP subunit genes rpoB and rpoC Inhibition of the RNAP switch
      region of O. tsutsugamushi by CorA is therefore a novel and highly potent target
      for antimicrobial therapy for scrub typhus.

PMID- 29358296
TI  - Population Pharmacokinetic Model-Based Evaluation of Standard Dosing Regimens for
      Cefuroxime Used in Coronary Artery Bypass Graft Surgery with Cardiopulmonary
      Bypass.
AB  - The purpose of this study was to investigate the population pharmacokinetics (PK)
      of cefuroxime in patients undergoing coronary artery bypass graft (CABG) surgery.
      In this observational pharmacokinetic study, multiple blood samples were
      collected over a 48-h interval of intravenous cefuroxime administration. The
      samples were analyzed by using a validated high-performance liquid chromatography
      (HPLC) method. Population pharmacokinetic models were developed using Monolix
      (version 4.4) software. Pharmacokinetic-pharmacodynamic (PD) simulations were
      performed to explore the ability of different dosage regimens to achieve the
      pharmacodynamic targets. A total of 468 blood samples from 78 patients were
      analyzed. The PK for cefuroxime were best described by a two-compartment model
      with between-subject variability on clearance, the volume of distribution of the
      central compartment, and the volume of distribution of the peripheral
      compartment. The clearance of cefuroxime was related to creatinine clearance
      (CLCR). Dosing simulations showed that standard dosing regimens of 1.5 g could
      achieve the PK-PD target of the percentage of the time that the free
      concentration is maintained above the MIC during a dosing interval (fTMIC) of 65%
      for an MIC of 8 mg/liter in patients with a CLCR of 30, 60, or 90 ml/min, whereas
      this dosing regimen failed to achieve the PK-PD target in patients with a CLCR of
      >=125 ml/min. In conclusion, administration of standard doses of 1.5 g three
      times daily provided adequate antibiotic prophylaxis in patients undergoing CABG
      surgery. Lower doses failed to achieve the PK-PD target. Patients with high CLCR
      values required either higher doses or shorter intervals of cefuroxime dosing. On
      the other hand, lower doses (1 g three times daily) produced adequate target
      attainment for patients with low CLCR values (<=30 ml/min).

PMID- 29358297
TI  - Cellular Pharmacokinetics and Intracellular Activity of Gepotidacin against
      Staphylococcus aureus Isolates with Different Resistance Phenotypes in Models of
      Cultured Phagocytic Cells.
AB  - Gepotidacin (GSK2140944), a novel triazaacenaphthylene bacterial topoisomerase
      inhibitor, is currently in clinical development for the treatment of bacterial
      infections. This study examined in vitro its activity against intracellular
      Staphylococcus aureus (involved in the persistent character of skin and skin
      structure infections) by use of a pharmacodynamic model and in relation to
      cellular pharmacokinetics in phagocytic cells. Compared to oxacillin, vancomycin,
      linezolid, daptomycin, azithromycin, and moxifloxacin, gepotidacin was (i) more
      potent intracellularly (the apparent bacteriostatic concentration [Cs ] was
      reached at an extracellular concentration about 0.7* its MIC and was not affected
      by mechanisms of resistance to the comparators) and (ii) caused a maximal
      reduction of the intracellular burden (maximum effect) of about -1.6 log10 CFU
      (which was better than that caused by linezolid, macrolides, and daptomycin and
      similar to that caused by moxifloxacin). After 24 h of incubation of infected
      cells with antibiotics at 100* their MIC, the intracellular persisting fraction
      was <0.1% with moxifloxacin, 0.5% with gepotidacin, and >1% with the other drugs.
      The accumulation and efflux of gepotidacin in phagocytes were very fast (kin and
      kout, ~0.3 min-1; the plateau was reached within 15 min) but modest
      (intracellular concentration-to-extracellular concentration ratio, ~1.6). In cell
      fractionation studies, about 40 to 60% of the drug was recovered in the soluble
      fraction and ~40% was associated with lysosomes in uninfected cells. In infected
      cells, about 20% of cell-associated gepotidacin was recovered in a sedimentable
      fraction that also contained bacteria. This study highlights the potential for
      further study of gepotidacin to fight infections where intracellular niches may
      play a determining role in bacterial persistence and relapses.

PMID- 29358298
TI  - Unraveling the Metabolic Routes of Retapamulin: Insights into Drug Development of
      Pleuromutilins.
AB  - Retapamulin, a semisynthetic pleuromutilin derivative, is exclusively used for
      the topical short-term medication of impetigo and staphylococcal infections. In
      the present study, we report that retapamulin is adequately and rapidly
      metabolized in vitro via various metabolic pathways, such as hydroxylation,
      including mono-, di-, and trihydroxylation, and demethylation. Like tiamulin and
      valnemulin, the major metabolic routes of retapamulin were hydroxylation at the
      2beta and 8alpha positions of the mutilin moiety. Moreover, in vivo metabolism
      concurred with the results of the in vitro assays. Additionally, we observed
      significant interspecies differences in the metabolism of retapamulin. Until now,
      modifying the side chain was the mainstream method for new drug discovery of the
      pleuromutilins. This approach, however, could not resolve the low bioavailability
      and short efficacy of the drugs. Considering the rapid metabolism of the
      pleuromutilins mediated by cytochrome P450 enzymes, we propose that blocking the
      active metabolic site (C-2 and C-8 motif) or administering the drug in
      combination with cytochrome P450 enzyme inhibitors is a promising pathway in the
      development of novel pleuromutilin drugs with slow metabolism and long efficacy.

PMID- 29358300
TI  - January 22nd Question.

PMID- 29358301
TI  - Money to transform NHS services is diverted to reducing deficits, watchdog finds.

PMID- 29358299
TI  - Shaping Substrate Selectivity in a Broad-Spectrum Metallo-beta-Lactamase.
AB  - Metallo-beta-lactamases (MBLs) are the major group of carbapenemases produced by
      bacterial pathogens. The design of MBL inhibitors has been limited by, among
      other issues, incomplete knowledge about how these enzymes modulate substrate
      recognition. While most MBLs are broad-spectrum enzymes, B2 MBLs are exclusive
      carbapenemases. This narrower substrate profile has been attributed to a sequence
      insertion present in B2 enzymes that limits accessibility to the active site. In
      this work, we evaluate the role of sequence insertions naturally occurring in the
      B2 enzyme Sfh-I and in the broad-spectrum B1 enzyme SPM-1. We engineered a
      chimeric protein in which the sequence insertion of SPM-1 was replaced by the one
      present in Sfh-I. The chimeric variant is a selective cephalosporinase, revealing
      that the substrate profile of MBLs can be further tuned depending on the protein
      context. These results also show that the stable scaffold of MBLs allows a
      modular engineering much richer than the one observed in nature.

PMID- 29358302
TI  - Public will have to pay L220bn for PFI until 2040, NAO calculates.

PMID- 29358303
TI  - GPs in Scotland vote to accept new contract.

PMID- 29358304
TI  - The AMH genotype (rs10407022 T>G) is associated with circulating AMH levels in
      boys, but not in girls.
AB  - OBJECTIVE: Fetal anti-Mullerian hormone (AMH) is responsible for normal male
      sexual differentiation, and circulating AMH is used as a marker of testicular
      tissue in newborns with disorders of sex development. Little is known about the
      mechanism of action in postnatal life. A recent genome wide association study
      (GWAS) reported genetic variation of AMH affecting AMH levels in young men. This
      study investigated the effect of genetic variation of AMH and AMH type II
      receptor (AMHR2) (AMHrs10407022 T>G and AMHR2rs11170547 C>T) on circulating
      reproductive hormone levels and pubertal onset in boys and girls. DESIGN AND
      METHODS: This study is a combined longitudinal and cross-sectional study in
      healthy Danish boys and girls from the general population. We included 658 boys
      aged 5.8-19.8 years and 320 girls aged 5.6-16.5 years. The main outcome measures
      were genotyping of AMH and AMHR2, pubertal staging and serum levels of
      reproductive hormones. RESULTS: AMHrs10407022T>G was associated with higher serum
      levels of AMH in prepubertal boys (TT: 575 pmol/L vs TG: 633 pmol/L vs GG: 837
      pmol/L, P = 0.002) and adolescents (TT: 44 pmol/L vs TG: 58 pmol/L vs GG: 79
      pmol/L, P < 0.001). Adolescent boys carrying the genetic variation also had lower
      levels of LH (TT: 3.0 IU/L vs TG: 2.8 IU/L vs GG: 1.8 IU/L, P = 0.012). Hormone
      levels in girls and pubertal onset in either sex did not seem to be profoundly
      affected by the genotypes. CONCLUSION: Our findings support recent GWAS results
      in young adults and expand our understanding of genetic variation affecting AMH
      levels even in boys prior to the pubertal decline of circulating AMH.

PMID- 29358305
TI  - Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells
      exhibit impaired neurodifferentiation.
AB  - Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder
      characterized by the absence of beta-hexosaminidase A and B activity and the
      concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features
      catastrophic neurodegeneration and death in early childhood. How the lysosomal
      accumulation of ganglioside might affect the early development of the nervous
      system is not understood. Recently, cerebral organoids derived from induced
      pluripotent stem (iPS) cells have illuminated early developmental events altered
      by disease processes. To develop an early neurodevelopmental model of Sandhoff
      disease, we first generated iPS cells from the fibroblasts of an infantile
      Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those
      iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic
      controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB
      corrected iPS cell clones to generate cerebral organoids that modeled the first
      trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB
      corrected organoids, accumulated GM2 ganglioside and exhibited increased size and
      cellular proliferation compared with the HEXB-corrected organoids. Whole
      transcriptome analysis demonstrated that development was impaired in the Sandhoff
      disease organoids, suggesting that alterations in neuronal differentiation may
      occur during early development in the GM2 gangliosidoses.

PMID- 29358306
TI  - PARK7 regulates inflammation-induced pro-labour mediators in myometrial and
      amnion cells.
AB  - Preterm birth is a prevalent cause of neonatal deaths worldwide. Inflammation has
      been implicated in spontaneous preterm birth involved in the processes of uterine
      contractility and membrane rupture. Parkinson protein 7 (PARK7) has been found to
      play an inflammatory role in non-gestational tissues. The aims of this study were
      to determine the expression of PARK7 in myometrium and fetal membranes with
      respect to term labour onset and to elucidate the effect of PARK7 silencing in
      primary myometrium and amnion cells on pro-inflammatory and pro-labour mediators.
      PARK7 mRNA expression was higher in term myometrium and fetal membranes from
      women in labour compared to non-labouring samples and in amnion from preterm
      deliveries with chorioamnionitis. In human primary myometrial cells transfected
      with PARK7 siRNA (siPARK7), there was a significant decrease in IL1B, TNF, fsl-1
      and poly(I:C)-induced expression of pro-inflammatory cytokine IL6, chemokines
      (CXCL8, CCL2), adhesion molecule ICAM1, prostaglandin PGF2alpha and its receptor
      PTGFR. Similarly, amnion cells transfected with siPARK7 displayed a decrease in
      IL1B-induced expression of IL6, CXCL8 and ICAM1. In myometrial cells transfected
      with siPARK7, there was a significant reduction of NF-kappaB RELA transcriptional
      activity when stimulated with fsl-1, flagellin and poly(I:C), but not with IL1B
      or TNF. Collectively, our novel data describe a role for PARK7 in regulating
      inflammation-induced pro-inflammatory and pro-labour mediators in human
      myometrial and amnion cells.

PMID- 29358307
TI  - miR-422a inhibits osteosarcoma proliferation by targeting BCL2L2 and KRAS.
AB  - Osteosarcoma is the most common primary malignant bone tumor in children and
      adolescents. However, the underlying mechanism of osteosarcoma carcinogenesis and
      progression remains unknown. In the present study, we evaluated the expression
      profile of miRNAs in osteosarcoma tissues and the adjacent normal tissues. We
      found that the expression of miR-422a was down-regulated in osteosarcoma tissues
      and cell lines. In addition, we observed significantly elevated levels of
      repressive H3K9me3 and H3K27me3 and decreased active H3K4me3 on the promote
      region of miR-422a in osteosarcoma cells and clinical samples. Furthermore, up
      regulation of miR-422a exhibited both in vitro and in vivo anti-tumor effects by
      inhibiting osteosarcoma cell growth and inducing apoptosis and cell cycle arrest.
      We also found that miR-422a targeted BCL2L2 and KRAS and negatively regulated
      their protein expression. Furthermore, restoration of miR-422a and knockdown of
      BCL2L2 and KRAS promoted apoptosis and induce cell cycle arrest in osteosarcoma
      cells. Taken together, the present study demonstrates that miR-422a may serve as
      a tumor suppressor in osteosarcoma via inhibiting BCL2L2 and KRAS translation
      both in vitro and in vivo Therefore, miR-422a could be developed as a novel
      therapeutic target in osteosarcoma.

PMID- 29358308
TI  - beta-adrenoceptor activation increased VAMP-2 and syntaxin-4 in secretory
      granules are involved in protein secretion of submandibular gland through the
      PKA/F-actin pathway.
AB  - Autologous submandibular gland transplantation is an effective treatment for
      severe dry eye syndrome. However, the protein secretion in transplanted gland is
      altered by a mechanism that remains to be elucidated. In the present study, we
      found that beta1-adrenoceptor (beta1-AR) and beta2-AR expression and the
      phosphorylation of the downstream molecule protein kinase A (PKA) were elevated
      in transplanted submandibular glands obtained from epiphora patients.
      Synaptobrevin/vesicle-associated membrane protein 2 (VAMP-2) interacted with
      syntaxin-4 and actin in human submandibular gland. The contents of syntaxin-4 and
      actin interacting with VAMP-2 were increased in transplanted gland. Moreover,
      VAMP-2 and syntaxin-4 expression in the secretory granule fraction, and VAMP-2
      expression in the membrane protein fraction were increased in isoproterenol
      treated and transplanted glands. Isoproterenol increased F-actin polymerization
      in the apical and lateral regions of the cytoplasm in both control and
      transplanted glands. Inhibiting PKA activity and/or F-actin formation abolished
      the isoproterenol-enhanced expression of VAMP-2 and syntaxin-4 in the secretory
      granule fraction and the isoproterenol-enhanced expression of VAMP-2 in the
      membrane protein fraction. Taken together, these results indicate that the
      activation of beta-ARs induces secretory granules and cell membrane fusion via
      the interaction of VAMP-2 and syntaxin-4 in a PKA- and F-actin-dependent manner
      in human submandibular gland. Up-regulated beta-ARs might participate in altering
      protein secretion in transplanted submandibular gland by promoting the
      interaction of VAMP-2 with syntaxin-4.

PMID- 29358309
TI  - The roles of interleukins in perfusion recovery after peripheral arterial
      disease.
AB  - In peripheral arterial disease (PAD) patients, occlusions in the major arteries
      that supply the leg makes blood flow dependent on the capacity of
      neovascularization. There is no current medication that is able to increase
      neovascularization to the ischemic limb and directly treat the primary problem of
      PAD. An increasing body of evidence supports the notion that inflammation plays
      an important role in the vascular remodeling and perfusion recovery after PAD.
      Interleukins (ILs), a group of proteins produced during inflammation, have been
      considered to be important for angiogenesis and arteriogenesis after tissue
      ischemia. This review summarizes the latest clinical and experimental
      developments of the role of ILs in blood perfusion recovery after PAD.

PMID- 29358311
TI  - beta-Elemene inhibits the proliferation of primary human airway granulation
      fibroblasts by down-regulating canonical Wnt/beta-catenin pathway.
AB  - Benign airway stenosis is a clinical challenge because of recurrent granulation
      tissues. Our previous study proved that a Chinese drug, beta-elemene, could
      effectively inhibit the growth of fibroblasts cultured from hyperplastic human
      airway granulation tissues, which could slow down the progression of this
      disease. The purpose of the present study is to find out the mechanism for this
      effect. We cultured fibroblasts from normal human airway tissues and human airway
      granulation tissues. These cells were cultured with 160 MUg/ml normal saline
      (NS), different doses of beta-elemene, or 10 ng/ml canonical Wnt/beta-catenin
      pathway inhibitor (Dickkopf-1, DKK-1). The proliferation rate of cells and the
      expression of six molecules involved in canonical Wnt/beta-catenin pathway,
      Wnt3a, glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, alpha-smooth
      muscle actin (alpha-SMA), transforming growth factor-beta (TGF-beta), and
      Collagen I (Col-I), were measured. At last, we used canonical Wnt/beta-catenin
      pathway activator (LiCl) to further ascertain the mechanism of beta-elemene.
      Canonical Wnt/beta-catenin pathway is activated in human airway granulation
      fibroblasts. beta-Elemene didn't affect normal human airway fibroblasts; however,
      it had a dose-responsive inhibitive effect on the proliferation and expression of
      Wnt3a, non-active GSK-3beta, beta-catenin, alpha-SMA, TGF-beta, and Col-I of
      human airway granulation fibroblasts. More importantly, it had the same effect on
      the expression and nuclear translocation of active beta-catenin. All these
      effects were similar to 10 ng/ml DKK-1 and could be attenuated by 10 mM LiCl.
      Thus, beta-elemene inhibits the proliferation of primary human airway granulation
      fibroblasts by down-regulating canonical Wnt/beta-catenin pathway. This pathway
      is possibly a promising target to treat benign tracheobronchial stenosis.

PMID- 29358312
TI  - Government is not doing enough to improve children's health, paediatricians warn.

PMID- 29358310
TI  - 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol: a promising new anticancer
      compound.
AB  - The 7-nitro-2,1,3-nitrobenzoxadiazole (NBD) derivatives are a series of compounds
      containing the NBD scaffold that are not glutathione (GSH) peptidomimetics, and
      result in a strong inhibition of glutathione S-transferases (GSTs). Growing
      evidences highlight their pivotal roles and outstanding anticancer activity in
      different tumor models. In particular, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)
      hexanol (NBDHEX) is extensively studied, which is a very efficient inhibitor of
      GSTP1-1. It triggers apoptosis in several tumor cell lines and this cytotoxic
      activity is observed at micro and submicromolar concentrations. Importantly,
      studies have shown that NBDHEX acts as an anticancer drug by inhibiting GSTs
      catalytic activity, avoiding inconvenience of the inhibitor extrusion from the
      cell by specific pumps and disrupting the interaction between the GSTP1-1 and key
      signaling effectors. Additionally, some researchers also have discovered that
      NBDHEX can act as late-phase autophagy inhibitor, which opens new opportunities
      to fully exploit its therapeutic potential. In this review, we summarize the
      advantages, anticancer mechanisms, and analogs of this compound, which will
      establish the basis on the usage of NBDHEX in clinical applications in future.

PMID- 29358314
TI  - Patient experience of general practice and use of emergency hospital services in
      England: regression analysis of national cross-sectional time series data.
AB  - BACKGROUND: The UK Government has introduced several national policies to improve
      access to primary care. We examined associations between patient experience of
      general practice and rates of visits to accident and emergency (A&E) departments
      and emergency hospital admissions in England. METHODS: The study included 8124
      general practices between 2011-2012 and 2013-2014. Outcome measures were annual
      rates of A&E visits and emergency admissions by general practice population,
      according to administrative hospital records. Explanatory variables included
      three patient experience measures from the General Practice Patient Survey:
      practice-level means of experience of making an appointment, satisfaction with
      opening hours and overall experience (on 0-100 scales). The main analysis used
      random-effects Poisson regression for cross-sectional time series. Five
      sensitivity analyses examined changes in model specification. RESULTS: Mean
      practice-level rates of A&E visits and emergency admissions increased from 2011
      2012 to 2013-2014 (310.3-324.4 and 98.8-102.9 per 1000 patients). Each patient
      experience measure decreased; for example, mean satisfaction with opening hours
      was 79.4 in 2011-2012 and 76.6 in 2013-2014. In the adjusted regression analysis,
      an SD increase in experience of making appointments (equal to 9 points) predicted
      decreases of 1.8% (95% CI -2.4% to -1.2%) in A&E visit rates and 1.4% (95% CI 
      1.9% to -0.9%) in admission rates. This equalled 301 174 fewer A&E visits and 74
      610 fewer admissions nationally per year. Satisfaction with opening hours and
      overall experience were not consistently associated with either outcome measure
      across the main and sensitivity analyses. CONCLUSIONS: Associations between
      patient experience of general practice and use of emergency hospital services
      were small or inconsistent. In England, realistic short-term improvements in
      patient experience of general practice may only have modest effects on A&E visits
      and emergency admissions.

PMID- 29358313
TI  - Symptom-Disease Pair Analysis of Diagnostic Error (SPADE): a conceptual framework
      and methodological approach for unearthing misdiagnosis-related harms using big
      data.
AB  - BACKGROUND: The public health burden associated with diagnostic errors is likely
      enormous, with some estimates suggesting millions of individuals are harmed each
      year in the USA, and presumably many more worldwide. According to the US National
      Academy of Medicine, improving diagnosis in healthcare is now considered 'a
      moral, professional, and public health imperative.' Unfortunately, well
      established, valid and readily available operational measures of diagnostic
      performance and misdiagnosis-related harms are lacking, hampering progress.
      Existing methods often rely on judging errors through labour-intensive human
      reviews of medical records that are constrained by poor clinical documentation,
      low reliability and hindsight bias. METHODS: Key gaps in operational measurement
      might be filled via thoughtful statistical analysis of existing large clinical,
      billing, administrative claims or similar data sets. In this manuscript, we
      describe a method to quantify and monitor diagnostic errors using an approach we
      call 'Symptom-Disease Pair Analysis of Diagnostic Error' (SPADE). RESULTS: We
      first offer a conceptual framework for establishing valid symptom-disease pairs
      illustrated using the well-known diagnostic error dyad of dizziness-stroke. We
      then describe analytical methods for both look-back (case-control) and look
      forward (cohort) measures of diagnostic error and misdiagnosis-related harms
      using 'big data'. After discussing the strengths and limitations of the SPADE
      approach by comparing it to other strategies for detecting diagnostic errors, we
      identify the sources of validity and reliability that undergird our approach.
      CONCLUSION: SPADE-derived metrics could eventually be used for operational
      diagnostic performance dashboards and national benchmarking. This approach has
      the potential to transform diagnostic quality and safety across a broad range of
      clinical problems and settings.

PMID- 29358316
TI  - Ras-Mediated Activation of the Raf Family Kinases.
AB  - The extracellular signal-regulated kinase (ERK) cascade comprised of the Raf,
      MEK, and ERK protein kinases constitutes a key effector cascade used by the Ras
      GTPases to relay signals regulating cell growth, survival, proliferation, and
      differentiation. Of the ERK cascade components, the regulation of the Raf kinases
      is by far the most complex, involving changes in subcellular localization,
      protein and lipid interactions, as well as alterations in the Raf phosphorylation
      state. The Raf kinases interact directly with active, membrane-localized Ras, and
      this interaction is often the first step in the Raf activation process, which
      ultimately results in ERK activation and the downstream phosphorylation of
      cellular targets that will specify a particular biological response. Here, we
      will examine our current understanding of how Ras promotes Raf activation,
      focusing on the molecular mechanisms that contribute to the Raf
      activation/inactivation cycle.

PMID- 29358315
TI  - Effector T Cells in Multiple Sclerosis.
AB  - Multiple sclerosis (MS) has long been considered a CD4 T-cell disease, primarily
      because of the findings that the strongest genetic risk for MS is the major
      histocompatibility complex (MHC) class II locus, and that T cells play a central
      role in directing the immune response. The importance that the T helper (Th)1
      cytokine, interferon gamma (IFN-gamma), and the Th17 cytokine, interleukin (IL)
      17, play in MS pathogenesis is indicated by recent clinical trial data by the
      enhanced presence of Th1/Th17 cells in central nervous system (CNS) tissue,
      cerebrospinal fluid (CSF), and blood, and by research on animal models of MS,
      such as experimental autoimmune encephalomyelitis (EAE). Although the majority of
      research on MS pathogenesis has centered on the role of effector CD4 T cells,
      accumulating data suggests that CD8 T cells may play a significant role in the
      human disease. In fact, in contrast to most animal models, the primary T cell
      found in the CNS in patients with MS, is the CD8 T cell. As patient-derived
      effector T cells are also resistant to mechanisms of dominant tolerance such as
      that induced by interaction with regulatory T cells (Tregs), their reduced
      response to regulation may also contribute to the unchecked effector T-cell
      activity in patients with MS. These concepts will be discussed below.

PMID- 29358317
TI  - Clinical Course of Multiple Sclerosis.
AB  - The 1996 originally established multiple sclerosis (MS) subtypes, based solely on
      clinical impression and consensus, were revised in 2013 to review potential
      imaging and biological correlates and to reflect recently identified clinical
      aspects of MS. As a result, potential new disease phenotypes, radiologically
      isolated syndrome, and clinically isolated syndrome were considered along with
      the addition of two new descriptor subtypes: activity and progression applied to
      relapsing remitting and progressive MS phenotypes. In this way, the description
      of an individual patient's disease course is refined and provides temporal
      information about the ongoing disease process. There is still a lack of imaging
      and biological markers that would distinguish MS phenotypes and prognosticate the
      disease course on an individual patient's level, creating a pressing need for
      large collaborative research efforts in this field.

PMID- 29358318
TI  - Regulation of Bone Remodeling by Parathyroid Hormone.
AB  - Parathyroid hormone (PTH) exerts profound effects on skeletal homeostasis through
      multiple cellular and molecular mechanisms. Continuous hyperparathyroidism causes
      net loss of bone mass, despite accelerating bone formation by osteoblasts.
      Intermittent treatment with PTH analogs represents the only Food and Drug
      Administration (FDA)-approved bone anabolic osteoporosis treatment strategy.
      Functional PTH receptors are present on cells of the osteoblast lineage, ranging
      from early skeletal stem cells to matrix-embedded osteocytes. In addition, bone
      remodeling by osteoclasts liberates latent growth factors present within bone
      matrix. Here, we will provide an overview of the multiple cellular and molecular
      mechanisms through which PTH influences bone homeostasis. Notably, net skeletal
      effects of continuous versus intermittent can differ significantly. Where
      possible, we will highlight mechanisms through which continuous
      hyperparathyroidism leads to bone loss, and through which intermittent
      hyperparathyroidism boosts bone mass. Given the therapeutic usage of intermittent
      PTH (iPTH) treatment for osteoporosis, particular attention will be paid toward
      mechanisms underlying the bone anabolic effects of once daily PTH administration.

PMID- 29358319
TI  - Magnetic Resonance Imaging in Multiple Sclerosis.
AB  - Since its technical development in the early 1980s, magnetic resonance imaging
      (MRI) has quickly been adopted as an essential tool in supporting the diagnosis,
      longitudinal monitoring, evaluation of therapeutic response, and scientific
      investigations in multiple sclerosis (MS). The clinical usage of MRI has
      increased in parallel with technical innovations in the technique itself; the
      widespread adoption of clinically routine MRI at 1.5T has allowed sensitive
      qualitative and quantitative assessments of macroscopic central nervous system
      (CNS) inflammatory demyelinating lesions and tissue atrophy. However,
      conventional MRI lesion measures lack specificity for the underlying MS pathology
      and only weakly correlate with clinical status. Higher field strength units and
      newer, advanced MRI techniques offer increased sensitivity and specificity in the
      detection of disease activity and disease severity. This review summarizes the
      current status and future prospects regarding the role of MRI in the
      characterization of MS-related brain and spinal cord involvement.

PMID- 29358320
TI  - Multiple Sclerosis Pathology.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system (CNS), which gives rise to focal lesions in the gray and
      white matter and to diffuse neurodegeneration in the entire brain. In this
      review, the spectrum of MS lesions and their relation to the inflammatory process
      is described. Pathology suggests that inflammation drives tissue injury at all
      stages of the disease. Focal inflammatory infiltrates in the meninges and the
      perivascular spaces appear to produce soluble factors, which induce demyelination
      or neurodegeneration either directly or indirectly through microglia activation.
      The nature of these soluble factors, which are responsible for demyelinating
      activity in sera and cerebrospinal fluid of the patients, is currently undefined.
      Demyelination and neurodegeneration is finally accomplished by oxidative injury
      and mitochondrial damage leading to a state of "virtual hypoxia."

PMID- 29358321
TI  - Regulation of Astrocyte Functions in Multiple Sclerosis.
AB  - Astrocytes play complex roles in health and disease. Here, we review recent
      findings on molecular pathways that control astrocyte function in multiple
      sclerosis (MS) as well as new tools for their investigation. In particular, we
      describe positive and negative regulators of astrocyte-mediated pathogenesis in
      MS, such as sphingolipid metabolism and aryl hydrocarbon receptor signaling,
      respectively. In addition, we also discuss the issue of astrocyte heterogeneity
      and its relevance for the contribution of astrocytes to MS pathogenesis. Finally,
      we discuss how new genomic tools could transform the study of astrocyte biology
      in MS.

PMID- 29358322
TI  - B-Cell Therapies in Multiple Sclerosis.
AB  - B cells play a vital function in multiple sclerosis (MS) pathogenesis through an
      array of effector functions. All currently approved MS disease-modifying
      therapies alter the frequency, phenotype, or homing of B cells in one way or
      another. The importance of this mechanism of action has been reinforced with the
      successful development and clinical testing of B-cell-depleting monoclonal
      antibodies that target the CD20 surface antigen. Ocrelizumab, a humanized anti
      CD20 monoclonal antibody, was approved by the Food and Drug Administration (FDA)
      in March 2017 after pivotal trials showed dramatic reductions in inflammatory
      disease activity in relapsing MS as well as lessening of disability progression
      in primary progressive MS. These and other clinical studies place B cells at the
      center of the inflammatory cascade in MS and provide a launching point for
      development of therapies that target selective pathogenic B-cell populations.

PMID- 29358323
TI  - Unraveling the molecular mechanism of interactions of the Rho GTPases Cdc42 and
      Rac1 with the scaffolding protein IQGAP2.
AB  - IQ motif-containing GTPase-activating proteins (IQGAPs) are scaffolding proteins
      playing central roles in cell-cell adhesion, polarity, and motility. The Rho
      GTPases Cdc42 and Rac1, in their GTP-bound active forms, interact with all three
      human IQGAPs. The IQGAP-Cdc42 interaction promotes metastasis by enhancing actin
      polymerization. However, despite their high sequence identity, Cdc42 and Rac1
      differ in their interactions with IQGAP. Two Cdc42 molecules can bind to the Ex
      domain and the RasGAP site of the GTPase-activating protein (GAP)-related domain
      (GRD) of IQGAP and promote IQGAP dimerization. Only one Rac1 molecule might bind
      to the RasGAP site of GRD and may not facilitate the dimerization, and the exact
      mechanism of Cdc42 and Rac1 binding to IQGAP is unclear. Using all-atom molecular
      dynamics simulations, site-directed mutagenesis, and Western blotting, we
      unraveled the detailed mechanisms of Cdc42 and Rac1 interactions with IQGAP2. We
      observed that Cdc42 binding to the Ex-domain of GRD of IQGAP2 (GRD2) releases the
      Ex-domain at the C-terminal region of GRD2, facilitating IQGAP2 dimerization.
      Cdc42 binding to the Ex-domain promoted allosteric changes in the RasGAP site,
      providing a binding site for the second Cdc42 in the RasGAP site. Of note, the
      Cdc42 "insert loop" was important for the interaction of the first Cdc42 with the
      Ex-domain. By contrast, differences in Rac1 insert-loop sequence and structure
      precluded its interaction with the Ex-domain. Rac1 could bind only to the RasGAP
      site of apo-GRD2 and could not facilitate IQGAP2 dimerization. Our detailed
      mechanistic insights help decipher how Cdc42 can stimulate actin polymerization
      in metastasis.

PMID- 29358324
TI  - The CD300e molecule in mice is an immune-activating receptor.
AB  - CD300 molecules (CD300s) belong to paired activating and inhibitory receptor
      families, which mediate immune responses. Human CD300e (hCD300e) is expressed in
      monocytes and myeloid dendritic cells and transmits an immune-activating signal
      by interacting with DNAX-activating protein 12 (DAP12). However, the CD300e
      ortholog in mice (mCD300e) is poorly characterized. Here, we found that mCD300e
      is also an immune-activating receptor. We found that mCD300e engagement triggers
      cytokine production in mCD300e-transduced bone marrow-derived mast cells (BMMCs).
      Loss of DAP12 and another signaling protein, FcRgamma, did not affect surface
      expression of transduced mCD300e, but abrogated mCD300e-mediated cytokine
      production in the BMMCs. Co-immunoprecipitation experiments revealed that mCD300e
      physically interacts with both FcRgamma and DAP12, suggesting that mCD300e
      delivers an activating signal via these two proteins. Binding and reporter assays
      with the mCD300e extracellular domain identified sphingomyelin as a ligand of
      both mCD300e and hCD300e. Notably, the binding of sphingomyelin to mCD300e
      stimulated cytokine production in the transduced BMMCs in an FcRgamma- and DAP12
      dependent manner. Flow cytometric analysis with an mCD300e-specific Ab disclosed
      that mCD300e expression is highly restricted to CD115+Ly-6Clow/int peripheral
      blood monocytes, corresponding to CD14dim/+CD16+ human nonclassical and
      intermediate monocytes. Loss of FcRgamma or DAP12 lowered the surface expression
      of endogenous mCD300e in the CD115+Ly-6Clow/int monocytes. Stimulation with
      sphingomyelin failed to activate the CD115+Ly-6Clow/int mouse monocytes, but
      induced hCD300e-mediated cytokine production in the CD14dimCD16+ human monocytes.
      Taken together, these observations indicate that mCD300e recognizes sphingomyelin
      and thereby regulates nonclassical and intermediate monocyte functions through
      FcRgamma and DAP12.

PMID- 29358325
TI  - Mapping allosteric linkage to channel gating by extracellular domains in the
      human epithelial sodium channel.
AB  - The epithelial sodium channel (ENaC) mediates sodium absorption in lung, kidney,
      and colon epithelia. Channels in the ENaC/degenerin family possess an
      extracellular region that senses physicochemical changes in the extracellular
      milieu and allosterically regulates the channel opening. Proteolytic cleavage
      activates the ENaC opening, by the removal of specific segments in the finger
      domains of the alpha- and gamma ENaC-subunits. Cleavage causes perturbations in
      the extracellular region that propagate to the channel gate. However, it is not
      known how the channel structure mediates the propagation of activation signals
      through the extracellular sensing domains. Here, to identify the structure
      function determinants that mediate allosteric ENaC activation, we performed MD
      simulations, thiol modification of residues substituted by cysteine, and voltage
      clamp electrophysiology recordings. Our simulations of an ENaC heterotetramer,
      alpha1betaalpha2gamma, in the proteolytically cleaved and uncleaved states
      revealed structural pathways in the alpha-subunit that are responsible for ENaC
      proteolytic activation. To validate these findings, we performed site-directed
      mutagenesis to introduce cysteine substitutions in the extracellular domains of
      the alpha-, beta-, and gamma ENaC-subunits. Insertion of a cysteine at the alpha
      subunit Glu557 site, predicted to stabilize a closed state of ENaC, inhibited
      ENaC basal activity and retarded the kinetics of proteolytic activation by 2
      fold. Our results suggest that the lower palm domain of alphaENaC is essential
      for ENaC activation. In conclusion, our integrated computational and experimental
      approach suggests key structure-function determinants for ENaC proteolytic
      activation and points toward a mechanistic model for the allosteric communication
      in the extracellular domains of the ENaC/degenerin family channels.

PMID- 29358326
TI  - Oxysterol-binding protein-related protein 5 (ORP5) promotes cell proliferation by
      activation of mTORC1 signaling.
AB  - Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a
      large family of proteins that mainly function in lipid transport and sensing.
      ORP5 is an endoplasmic reticulum (ER)-anchored protein implicated in lipid
      transfer at the contact sites between the ER and other membranes. Recent studies
      indicate that ORP5 is also involved in cancer cell invasion and tumor
      progression. However, the molecular mechanism underlying ORP5's involvement in
      cancer is unclear. Here, we report that ORP5 promotes cell proliferation and
      motility of HeLa cells, an effect that depends on its functional OSBP-related
      domain (ORD). We also found that ORP5 depletion or substitutions of key residues
      located within ORP5-ORD and responsible for interactions with lipids interfered
      with cell proliferation, migration, and invasion. ORP5 interacted with the
      protein mechanistic target of rapamycin (mTOR), and this interaction also
      required ORP5-ORD. Of note, whereas ORP5 overexpression induced mTOR complex 1
      (mTORC1) activity, ORP5 down-regulation had the opposite effect. Finally, ORP5
      depleted cells exhibited impaired mTOR localization to lysosomes, which may have
      accounted for the blunted mTORC1 activation. Together, our results suggest that
      ORP5 expression is positively correlated with mTORC1 signaling and that ORP5
      stimulates cell proliferation, at least in part, by activating mTORC1.

PMID- 29358327
TI  - Low-level overexpression of p53 promotes warfarin-induced calcification of
      porcine aortic valve interstitial cells by activating Slug gene transcription.
AB  - The most frequently used oral anti-coagulant warfarin has been implicated in
      inducing calcification of aortic valve interstitial cells (AVICs), whereas the
      mechanism is not fully understood. The low-level activation of p53 is found to be
      involved in osteogenic transdifferentiation and calcification of AVICs. Whether
      p53 participates in warfarin-induced AVIC calcification remains unknown. In this
      study, we investigated the role of low-level p53 overexpression in warfarin
      induced porcine AVIC (pAVIC) calcification. Immunostaining, quantitative PCR, and
      Western blotting revealed that p53 was expressed in human and pAVICs and that p53
      expression was slightly increased in calcific human aortic valves compared with
      non-calcific valves. Terminal deoxynucleotidyltransferase-mediated dUTP nick end
      labeling staining indicated that apoptosis slightly increased in calcific aortic
      valves than in non-calcific valves. Warfarin treatment led to a low-level
      increase of p53 mRNA and protein in both pAVICs and mouse aortic valves. Low
      level overexpression of p53 in pAVICs via an adenovirus vector did not affect
      pAVIC apoptosis but promoted warfarin-induced calcium deposition and expression
      of osteogenic markers. shRNA-mediated p53 knockdown attenuated the pAVIC calcium
      deposition and osteogenic marker expression. Moreover, ChIP and luciferase assays
      showed that p53 was recruited to the slug promoter and activated slug expression
      in calcific pAVICs. Of note, overexpression of Slug increased osteogenic marker
      Runx2 expression, but not pAVIC calcium deposition, and Slug knockdown attenuated
      pAVIC calcification and p53-mediated pAVIC calcium deposition and expression of
      osteogenic markers. In conclusion, we found that p53 plays an important role in
      warfarin induced pAVIC calcification, and increased slug transcription by p53 is
      required for p53-mediated pAVIC calcification.

PMID- 29358328
TI  - A human xenobiotic nuclear receptor contributes to nonresponsiveness of
      Mycobacterium tuberculosis to the antituberculosis drug rifampicin.
AB  - Mycobacterium tuberculosis is the causative agent of tuberculosis (TB). It
      acquires phenotypic drug resistance inside macrophages, and this resistance
      mainly arises from host-induced stress. However, whether cellular drug-efflux
      mechanisms in macrophages contribute to nonresponsiveness of M. tuberculosis to
      anti-TB drugs is unclear. Here, we report that xenobiotic nuclear receptors
      mediate TB drug nonresponsiveness by modulating drug-efflux transporters in
      macrophages. This was evident from expression analysis of drug-efflux
      transporters in macrophages isolated from TB patients. Among patients harboring
      rifampicin-susceptible M. tuberculosis, we observed increased intracellular
      survival of M. tuberculosis upon rifampicin treatment of macrophages isolated
      from patients not responding to anti-TB drugs compared with macrophages from
      patients who did respond. Of note, M. tuberculosis infection and rifampicin
      exposure synergistically modulated macrophage drug-efflux transporters in vitro
      We also found that the xenobiotic nuclear receptor pregnane X receptor (PXR)
      modulates macrophage drug-efflux transporter expression and activity, which
      compromised the anti-TB efficacy of rifampicin. We further validated this finding
      in a TB mouse model in which use of the PXR antagonist ketoconazole rescued
      rifampicin anti-TB activity. We conclude that PXR activation in macrophages
      compromises the efficacy of the anti-TB drug rifampicin. Alternative therapeutic
      strategies, such as use of the rifampicin derivatives rifapentine and rifabutin,
      which do not activate PXR, or of a PXR antagonist, may be effective for tackling
      drug nonresponsiveness of M. tuberculosis that arises from drug-efflux systems of
      the host.

PMID- 29358329
TI  - Profilin reduces aggregation and phase separation of huntingtin N-terminal
      fragments by preferentially binding to soluble monomers and oligomers.
AB  - Huntingtin N-terminal fragments (Htt-NTFs) with expanded polyglutamine tracts
      form a range of neurotoxic aggregates that are associated with Huntington's
      disease. Here, we show that aggregation of Htt-NTFs, irrespective of
      polyglutamine length, yields at least three phases (designated M, S, and F) that
      are delineated by sharp concentration thresholds and distinct aggregate sizes and
      morphologies. We found that monomers and oligomers make up the soluble M phase,
      ~25-nm spheres dominate in the soluble S phase, and long, linear fibrils make up
      the insoluble F phase. Previous studies showed that profilin, an abundant
      cellular protein, reduces Htt-NTF aggregation and toxicity in cells. We confirm
      that profilin achieves its cellular effects through direct binding to the C
      terminal proline-rich region of Htt-NTFs. We show that profilin preferentially
      binds to Htt-NTF M-phase species and destabilizes aggregation and phase
      separation by shifting the concentration boundaries for phase separation to
      higher values through a process known as polyphasic linkage. Our experiments,
      aided by coarse-grained computer simulations and theoretical analysis, suggest
      that preferential binding of profilin to the M-phase species of Htt-NTFs is
      enhanced through a combination of specific interactions between profilin and
      polyproline segments and auxiliary interactions between profilin and
      polyglutamine tracts. Polyphasic linkage may be a general strategy that cells
      utilize to regulate phase behavior of aggregation-prone proteins. Accordingly,
      detailed knowledge of phase behavior and an understanding of how ligands modulate
      phase boundaries may pave the way for developing new therapeutics against a
      variety of aggregation-prone proteins.

PMID- 29358330
TI  - Histone variant H3.3-mediated chromatin remodeling is essential for paternal
      genome activation in mouse preimplantation embryos.
AB  - Derepression of chromatin-mediated transcriptional repression of paternal and
      maternal genomes is considered the first major step that initiates zygotic gene
      expression after fertilization. The histone variant H3.3 is present in both male
      and female gametes and is thought to be important for remodeling the paternal and
      maternal genomes for activation during both fertilization and embryogenesis.
      However, the underlying mechanisms remain poorly understood. Using our H3.3B-HA
      tagged mouse model, engineered to report H3.3 expression in live animals and to
      distinguish different sources of H3.3 protein in embryos, we show here that sperm
      derived H3.3 (sH3.3) protein is removed from the sperm genome shortly after
      fertilization and extruded from the zygotes via the second polar bodies (PBII)
      during embryogenesis. We also found that the maternal H3.3 (mH3.3) protein is
      incorporated into the paternal genome as early as 2 h postfertilization and is
      detectable in the paternal genome until the morula stage. Knockdown of maternal
      H3.3 resulted in compromised embryonic development both of fertilized embryos and
      of androgenetic haploid embryos. Furthermore, we report that mH3.3 depletion in
      oocytes impairs both activation of the Oct4 pluripotency marker gene and global
      de novo transcription from the paternal genome important for early embryonic
      development. Our results suggest that H3.3-mediated paternal chromatin remodeling
      is essential for the development of preimplantation embryos and the activation of
      the paternal genome during embryogenesis.

PMID- 29358332
TI  - Trypanosoma cruzi Produces the Specialized Proresolving Mediators Resolvin D1,
      Resolvin D5, and Resolvin E2.
AB  - Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD). CD is
      a persistent, lifelong infection affecting many organs, most notably the heart,
      where it may result in acute myocarditis and chronic cardiomyopathy. The
      pathological features include myocardial inflammation and fibrosis. In the Brazil
      strain-infected CD-1 mouse, which recapitulates many of the features of human
      infection, we found increased plasma levels of resolvin D1 (RvD1), a specialized
      proresolving mediator of inflammation, during both the acute and chronic phases
      of infection (>100 days postinfection) as determined by enzyme-linked
      immunosorbent assay (ELISA). Additionally, ELISA on lysates of trypomastigotes of
      both strains Tulahuen and Brazil revealed elevated levels of RvD1 compared with
      lysates of cultured epimastigotes of T. cruzi, tachyzoites of Toxoplasma gondii,
      trypomastigotes of Trypanosoma brucei, cultured L6E9 myoblasts, and culture
      medium containing no cells. Lysates of T. cruzi-infected myoblasts also displayed
      increased levels of RvD1. Lipid mediator metabolomics confirmed that the
      trypomastigotes of T. cruzi produced RvD1, RvD5, and RvE2, which have been
      demonstrated to modulate the host response to bacterial infections. Plasma RvD1
      levels may be both host and parasite derived. Since T. cruzi synthesizes
      specialized proresolving mediators of inflammation, as well as proinflammatory
      eicosanoids, such as thromboxane A2, one may speculate that by using these lipid
      mediators to modulate its microenvironment, the parasite is able to survive.

PMID- 29358331
TI  - LSD1 demethylase and the methyl-binding protein PHF20L1 prevent SET7
      methyltransferase-dependent proteolysis of the stem-cell protein SOX2.
AB  - The pluripotency-controlling stem-cell protein SRY-box 2 (SOX2) plays a pivotal
      role in maintaining the self-renewal and pluripotency of embryonic stem cells and
      also of teratocarcinoma or embryonic carcinoma cells. SOX2 is monomethylated at
      lysine 119 (Lys-119) in mouse embryonic stem cells by the SET7 methyltransferase,
      and this methylation triggers ubiquitin-dependent SOX2 proteolysis. However, the
      molecular regulators and mechanisms controlling SET7-induced SOX2 proteolysis are
      unknown. Here, we report that in human ovarian teratocarcinoma PA-1 cells,
      methylation-dependent SOX2 proteolysis is dynamically regulated by the LSD1
      lysine demethylase and a methyl-binding protein, PHD finger protein 20-like 1
      (PHF20L1). We found that LSD1 not only removes the methyl group from
      monomethylated Lys-117 (equivalent to Lys-119 in mouse SOX2), but it also
      demethylates monomethylated Lys-42 in SOX2, a reaction that SET7 also regulated
      and that also triggered SOX2 proteolysis. Our studies further revealed that
      PHF20L1 binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents
      SOX2 proteolysis. Down-regulation of either LSD1 or PHF20L1 promoted SOX2
      proteolysis, which was prevented by SET7 inactivation in both PA-1 and mouse
      embryonic stem cells. Our studies also disclosed that LSD1 and PHF20L1 normally
      regulate the growth of pluripotent mouse embryonic stem cells and PA-1 cells by
      preventing methylation-dependent SOX2 proteolysis. In conclusion, our findings
      reveal an important mechanism by which the stability of the pluripotency
      controlling stem-cell protein SOX2 is dynamically regulated by the activities of
      SET7, LSD1, and PHF20L1 in pluripotent stem cells.

PMID- 29358333
TI  - Ehrlichia chaffeensis TRP120 Effector Targets and Recruits Host Polycomb Group
      Proteins for Degradation To Promote Intracellular Infection.
AB  - Ehrlichia chaffeensis has a group of well-characterized type I secreted tandem
      repeat protein (TRP) effectors that have moonlighting capabilities. TRPs modulate
      various cellular processes, reprogram host gene transcription as nucleomodulins,
      function as ubiquitin ligases, and directly activate conserved host cell
      signaling pathways to promote E. chaffeensis infection. One TRP-interacting host
      target is polycomb group ring finger protein 5 (PCGF5), a member of the polycomb
      group (PcG) protein family and a component of the polycomb repressive complex 1
      (PRC1). The current study demonstrates that during early infection, PCGF5
      strongly colocalizes with TRP120 in the nucleus and later dramatically
      redistributes to the ehrlichial vacuole along with other PCGF isoforms. Ectopic
      expression and immunoprecipitation of TRP120 confirmed the interaction of TRP120
      with multiple different PCGF isoforms. At 48 h postinfection, a dramatic
      redistribution of PCGF isoforms from the nucleus to the ehrlichial vacuole was
      observed, which also temporally coincided with proteasomal degradation of PCGF
      isoforms and TRP120 expression on the vacuole. A decrease in PRC1-mediated
      repressive chromatin mark and an altered transcriptional activity in PRC1
      associated Hox genes primarily from HOXB and HOXC clusters were observed along
      with the degradation of PCGF isoforms, suggesting disruption of the PRC1 in E.
      chaffeensis-infected cells. Notably, small interfering RNA (siRNA)-mediated
      knockdown of PCGF isoforms resulted in significantly increased E. chaffeensis
      infection. This study demonstrates a novel strategy in which E. chaffeensis
      manipulates PRC complexes through interactions between TRP120 and PCGF isoforms
      to promote infection.

PMID- 29358335
TI  - Mycoplasma genitalium Nonadherent Phase Variants Arise by Multiple Mechanisms and
      Escape Antibody-Dependent Growth Inhibition.
AB  - Antigenic variation of the immunodominant MgpB and MgpC proteins has been
      suggested to be a mechanism of immune evasion of the human pathogen Mycoplasma
      genitalium, a cause of several reproductive tract disease syndromes. Phase
      variation resulting in the loss of adherence has also been documented, but the
      molecular mechanisms underlying this process and its role in pathogenesis are
      still poorly understood. In this study, we isolated and characterized 40
      spontaneous, nonadherent phase variants from in vitro-passaged M. genitalium
      cultures. In all cases, nonadherence was associated with the loss of MgpBC
      protein expression, attributable to sequence changes in the mgpBC expression
      site. Phase variants were grouped into seven classes on the basis of the nature
      of the mutation. Consistent with the established role of RecA in phase variation,
      31 (79.5%) variants arose via recombination with MgPa repeat regions that contain
      mgpBC variable sequences. The remaining mutants arose via nonsense or frameshift
      mutations. As expected, revertants were obtained for phase variants that were
      predicted to be reversible but not for those that arose via an irreversible
      mechanism. Furthermore, phase variants were enriched in M. genitalium cultures
      exposed to antibodies reacting to the extracellular, conserved C terminus of MgpB
      but not in cultures exposed to antibodies reacting to an intracellular domain of
      MgpB or the cytoplasmic HU protein. Genetic characterization of the antibody
      selected phase variants confirmed that they arose via reversible and irreversible
      recombination and point mutations within mgpBC These phase variants resisted
      antibody-mediated growth inhibition, suggesting that phase variation promotes
      immune evasion.

PMID- 29358334
TI  - The QseG Lipoprotein Impacts the Virulence of Enterohemorrhagic Escherichia coli
      and Citrobacter rodentium and Regulates Flagellar Phase Variation in Salmonella
      enterica Serovar Typhimurium.
AB  - The QseEF histidine kinase/response regulator system modulates expression of
      enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica serovar
      Typhimurium virulence genes in response to the host neurotransmitters epinephrine
      and norepinephrine. qseG, which encodes an outer membrane lipoprotein, is
      cotranscribed with qseEF in these enteric pathogens, but there is little
      knowledge of its role in virulence. Here, we found that in EHEC QseG interacts
      with the type III secretion system (T3SS) gate protein SepL and modulates the
      kinetics of attaching and effacing (AE) lesion formation on tissue-cultured
      cells. Moreover, an EHEC DeltaqseG mutant had reduced intestinal colonization in
      an infant rabbit model. Additionally, in Citrobacter rodentium, an AE lesion
      forming pathogen like EHEC, QseG is required for full virulence in a mouse model.
      In S Typhimurium, we found that QseG regulates the phase switch between the two
      flagellin types, FliC and FljB. In an S Typhimurium DeltaqseG mutant, the phase
      variable promoter for fljB is preferentially switched into the "on" position,
      leading to overproduction of this phase two flagellin. In infection of tissue
      cultured cells, the S Typhimurium DeltaqseG mutant provokes increased
      inflammatory cytokine production versus the wild type; in vivo, in a murine
      infection model, the DeltaqseG strain caused a more severe inflammatory response
      and was attenuated versus the wild-type strain. Collectively, our findings
      demonstrate that QseG is important for full virulence in several enteric
      pathogens and controls flagellar phase variation in S Typhimurium, and they
      highlight both the complexity and conservation of the regulatory networks that
      control the virulence of enteric pathogens.

PMID- 29358336
TI  - Screening and Genomic Characterization of Filamentous Hemagglutinin-Deficient
      Bordetella pertussis.
AB  - Despite high vaccine coverage, pertussis cases in the United States have
      increased over the last decade. Growing evidence suggests that disease resurgence
      results, in part, from genetic divergence of circulating strain populations away
      from vaccine references. The United States employs acellular vaccines
      exclusively, and current Bordetella pertussis isolates are predominantly
      deficient in at least one immunogen, pertactin (Prn). First detected in the
      United States retrospectively in a 1994 isolate, the rapid spread of Prn
      deficiency is likely vaccine driven, raising concerns about whether other
      acellular vaccine immunogens experience similar pressures, as further antigenic
      changes could potentially threaten vaccine efficacy. We developed an
      electrochemiluminescent antibody capture assay to monitor the production of the
      acellular vaccine immunogen filamentous hemagglutinin (Fha). Screening 722 U.S.
      surveillance isolates collected from 2010 to 2016 identified two that were both
      Prn and Fha deficient. Three additional Fha-deficient laboratory strains were
      also identified from a historic collection of 65 isolates dating back to 1935.
      Whole-genome sequencing of deficient isolates revealed putative, underlying
      genetic changes. Only four isolates harbored mutations to known genes involved in
      Fha production, highlighting the complexity of its regulation. The chromosomes of
      two Fha-deficient isolates included unexpected structural variation that did not
      appear to influence Fha production. Furthermore, insertion sequence disruption of
      fhaB was also detected in a previously identified pertussis toxin-deficient
      isolate that still produced normal levels of Fha. These results demonstrate the
      genetic potential for additional vaccine immunogen deficiency and underscore the
      importance of continued surveillance of circulating B. pertussis evolution in
      response to vaccine pressure.

PMID- 29358337
TI  - Characterization of the In Vitro Chlamydia pecorum Response to Gamma Interferon.
AB  - Chlamydia pecorum is an important intracellular bacterium that causes a range of
      diseases in animals, including a native Australian marsupial, the koala. In
      humans and animals, a gamma interferon (IFN-gamma)-mediated immune response is
      important for the control of intracellular bacteria. The present study tested the
      hypotheses that C. pecorum can escape IFN-gamma-mediated depletion of host cell
      tryptophan pools. In doing so, we demonstrated that, unlike Chlamydia
      trachomatis, C. pecorum is completely resistant to IFN-gamma in human epithelial
      cells. While the growth of C. pecorum was inhibited in tryptophan-deficient
      medium, it could be restored by the addition of kynurenine, anthranilic acid, and
      indole, metabolites that could be exploited by the gene products of the C.
      pecorum tryptophan biosynthesis operon. We also found that expression of trp
      genes was detectable only when C. pecorum was grown in tryptophan-free medium,
      with gene repression occurring in response to the addition of kynurenine,
      anthranilic acid, and indole. When grown in bovine kidney epithelial cells,
      bovine IFN-gamma also failed to restrict the growth of C. pecorum, while C.
      trachomatis was inhibited, suggesting that C. pecorum could use the same
      mechanisms to evade the immune response in vivo in its natural host. Highlighting
      the different mechanisms triggered by IFN-gamma, however, both species failed to
      grow in murine McCoy cells treated with murine IFN-gamma. This work confirms
      previous hypotheses about the potential survival of C. pecorum after IFN-gamma
      mediated host cell tryptophan depletion and raises questions about the immune
      pathways used by the natural hosts of C. pecorum to control the widespread
      pathogen.

PMID- 29358338
TI  - Quantitative Proteomics After Spinal Cord Injury (SCI) in a Regenerative and a
      Nonregenerative Stage in the Frog Xenopus laevis.
AB  - The capacity to regenerate the spinal cord after an injury is a coveted trait
      that only a limited group of nonmammalian organisms can achieve. In Xenopus
      laevis, this capacity is only present during larval or tadpole stages, but is
      absent during postmetamorphic frog stages. This provides an excellent model for
      comparative studies between a regenerative and a nonregenerative stage to
      identify the cellular and molecular mechanisms that explain this difference in
      regenerative potential. Here, we used iTRAQ chemistry to obtain a quantitative
      proteome of the spinal cord 1 day after a transection injury in regenerative and
      nonregenerative stage animals, and used sham operated animals as controls. We
      quantified a total of 6,384 proteins, with 172 showing significant differential
      expression in the regenerative stage and 240 in the nonregenerative stage, with
      an overlap of only 14 proteins. Functional enrichment analysis revealed that
      although the regenerative stage downregulated synapse/vesicle and mitochondrial
      proteins, the nonregenerative stage upregulated lipid metabolism proteins, and
      downregulated ribosomal and translation control proteins. Furthermore, STRING
      network analysis showed that proteins belonging to these groups are highly
      interconnected, providing interesting candidates for future functional studies.
      Data are available via ProteomeXchange with identifier PXD006993.

PMID- 29358339
TI  - Quantitative Proteomics of Strong and Weak Biofilm Formers of Enterococcus
      faecalis Reveals Novel Regulators of Biofilm Formation.
AB  - Enterococcus faecalis is a bacterial pathogen associated with both endodontic and
      systemic infections. The biofilm formation ability of E. faecalis plays a key
      role in its virulence and drug resistance attributes. The formation of E.
      faecalis biofilms on implanted medical devices often results in treatment
      failure. In the present study, we report protein markers associated with the
      biofilm formation ability of E. faecalis using iTRAQ-based quantitative
      proteomics approach. In order to elucidate the biofilm-associated protein
      markers, we investigated the proteome of strong and weak biofilm-forming E.
      faecalis clinical isolates in comparison with standard American Type Culture
      Collection (ATCC) control strains. Comparison of E. faecalis strong and weak
      biofilm-forming clinical isolates with ATCC control strains showed that proteins
      associated with shikimate kinase pathway and sulfate transport were up-regulated
      in the strong biofilm former, while proteins associated with secondary
      metabolites, cofactor biosynthesis, and tetrahydrofolate biosynthesis were down
      regulated. In the weak biofilm former, proteins associated with nucleoside and
      nucleotide biosynthesis were up-regulated, whereas proteins associated with
      sulfate and sugar transport were down-regulated. Further pathway and gene
      ontology analyses revealed that the major differences in biofilm formation arise
      from differences in metabolic activity levels of the strong and weak biofilm
      formers, with higher levels of metabolic activity observed in the weak biofilm
      former. The differences in metabolic activity could therefore be a major
      determinant of the biofilm ability of E. faecalis The new markers identified from
      this study can be further characterized in order to understand their exact role
      in E. faecalis biofilm formation ability. This, in turn, can lead to numerous
      therapeutic benefits in the treatment of this oral and systemic pathogen. The
      data has been deposited to the ProteomeXchange with identifier PXD006542.

PMID- 29358342
TI  - Routine Oxygen Supplementation in Acute Cardiovascular Disease: The End of a
      Paradigm?

PMID- 29358340
TI  - Simple, scalable, and ultrasensitive tip-based identification of protease
      substrates.
AB  - Proteases are in the center of many diseases, and consequently, proteases and
      their substrates are important drug targets as represented by an estimated 5-10%
      of all drugs under development. Mass spectrometry has been an indispensable tool
      for the discovery of novel protease substrates, particularly through the proteome
      scale enrichment of so-called N-terminal peptides representing endogenous protein
      N termini. Methods such as combined fractional diagonal chromatography
      (COFRADIC)1 and, later, terminal amine isotopic labeling of substrates (TAILS)
      have revealed numerous insights into protease substrates and consensus motifs. We
      present an alternative and simple protocol for N-terminal peptide enrichment,
      based on charge-based fractional diagonal chromatography (ChaFRADIC) and
      requiring only well-established protein chemistry and a pipette tip. Using iTRAQ
      8-plex, we quantified on average 2,073 +/- 52 unique N-terminal peptides from
      only 4.3 MUg per sample/channel, allowing the identification of proteolytic
      targets and consensus motifs. This high sensitivity may even allow working with
      clinical samples such as needle biopsies in the future. We applied our method to
      study the dynamics of staurosporine-induced apoptosis. Our data demonstrate an
      orchestrated regulation of specific pathways after 1.5 h, 3 h, and 6 h of
      treatment, with many important players of homeostasis targeted already after 1.5
      h. We additionally observed an early multilevel modulation of the splicing
      machinery both by proteolysis and phosphorylation. This may reflect the known
      role of alternative splicing variants for a variety of apoptotic genes, which
      seems to be a driving force of staurosporine-induced apoptosis.

PMID- 29358343
TI  - Protecting Life and Limb in Peripheral Artery Disease.

PMID- 29358341
TI  - Temporal Effects of Combined Birinapant and Paclitaxel on Pancreatic Cancer Cells
      Investigated via Large-Scale, Ion-Current-Based Quantitative Proteomics
      (IonStar).
AB  - Despite decades of effort, pancreatic adenocarcinoma (PDAC) remains an
      intractable clinical challenge. An insufficient understanding of mechanisms
      underlying tumor cell responses to chemotherapy contributes significantly to the
      lack of effective treatment regimens. Here, paclitaxel, a first-line
      chemotherapeutic agent, was observed to interact synergistically with birinapant,
      a second mitochondrial-derived activator of caspases mimetic. Therefore, we
      investigated molecular-level drug interaction mechanisms using comprehensive,
      reproducible, and well-controlled ion-current-based MS1 quantification (IonStar).
      By analyzing 40 biological samples in a single batch, we compared temporal
      proteomic responses of PDAC cells treated with birinapant and paclitaxel, alone
      and combined. Using stringent criteria (e.g. strict false-discovery-rate (FDR)
      control, two peptides/protein), we quantified 4069 unique proteins confidently
      (99.8% without any missing data), and 541 proteins were significantly altered in
      the three treatment groups, with an FDR of <1%. Interestingly, most of these
      proteins were altered only by combined birinapant/paclitaxel, and these
      predominantly represented three biological processes: mitochondrial function,
      cell growth and apoptosis, and cell cycle arrest. Proteins responsible for
      activation of oxidative phosphorylation, fatty acid beta-oxidation, and
      inactivation of aerobic glycolysis were altered largely by combined
      birinapant/paclitaxel compared with single drugs, suggesting the Warburg effect,
      which is critical for survival and proliferation of cancer cells, was alleviated
      by the combination treatment. Metabolic profiling was performed to confirm
      substantially greater suppression of the Warburg effect by the combined agents
      compared with either drug alone. Immunoassays confirmed proteomic data revealing
      changes in apoptosis/survival signaling pathways, such as inhibition of PI3K/AKT,
      JAK/STAT, and MAPK/ERK signal transduction, as well as induction of G2/M arrest,
      and showed the drug combination induced much more apoptosis than did single
      agents. Overall, this in-depth, large-scale proteomics study provided novel
      insights into molecular mechanisms underlying synergy of combined
      birinapant/paclitaxel and describes a proteomics/informatics pipeline that can be
      applied broadly to the development of cancer drug combination regimens.

PMID- 29358344
TI  - Standardized Definition of Structural Valve Degeneration for Surgical and
      Transcatheter Bioprosthetic Aortic Valves.
AB  - Bioprostheses are prone to structural valve degeneration, resulting in limited
      long-term durability. A significant challenge when comparing the durability of
      different types of bioprostheses is the lack of a standardized terminology for
      the definition of a degenerated valve. This issue becomes especially important
      when we try to compare the degeneration rate of surgically inserted and
      transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve
      International Data), proposes practical and standardized definitions of valve
      degeneration and provides recommendations for the timing of clinical and imaging
      follow-up assessments accordingly. Its goal is to improve the quality of research
      and clinical care for patients with deteriorated bioprostheses by providing
      objective and strict criteria that can be utilized in future clinical trials. We
      hope that the adoption of these criteria by both the cardiological and surgical
      communities will lead to improved comparability and interpretation of durability
      analyses.

PMID- 29358346
TI  - Asymptomatic ST-Segment-Elevation ECG in Patient With Kidney Failure.

PMID- 29358347
TI  - Letter by Koutsampasopoulos et al Regarding Article, "Evidence Supporting the
      Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection
      Fraction".

PMID- 29358348
TI  - Letter by Jin-shan and Xue-bin Regarding Article, "Evidence Supporting the
      Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection
      Fraction".

PMID- 29358349
TI  - Letter by Carbone et al Regarding Article, "Evidence Supporting the Existence of
      a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction".

PMID- 29358350
TI  - Response by Obokata and Borlaug to Letters Regarding Article, "Evidence
      Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With
      Preserved Ejection Fraction".

PMID- 29358351
TI  - Gravitational waves from a first-order electroweak phase transition: a brief
      review.
AB  - We review the production of gravitational waves by an electroweak first-order
      phase transition. The resulting signal is a good candidate for detection at next
      generation gravitational wave detectors, such as LISA. Detection of such a source
      of gravitational waves could yield information about physics beyond the Standard
      Model that is complementary to that accessible to current and near-future
      collider experiments. We summarize efforts to simulate and model the phase
      transition and the resulting production of gravitational waves.This article is
      part of the Theo Murphy meeting issue 'Higgs cosmology'.

PMID- 29358352
TI  - Higgs cosmology.
AB  - The discovery of the Higgs boson in 2012 and other results from the Large Hadron
      Collider have confirmed the standard model of particle physics as the correct
      theory of elementary particles and their interactions up to energies of several
      TeV. Remarkably, the theory may even remain valid all the way to the Planck scale
      of quantum gravity, and therefore it provides a solid theoretical basis for
      describing the early Universe. Furthermore, the Higgs field itself has unique
      properties that may have allowed it to play a central role in the evolution of
      the Universe, from inflation to cosmological phase transitions and the origin of
      both baryonic and dark matter, and possibly to determine its ultimate fate
      through the electroweak vacuum instability. These connections between particle
      physics and cosmology have given rise to a new and growing field of Higgs
      cosmology, which promises to shed new light on some of the most puzzling
      questions about the Universe as new data from particle physics experiments and
      cosmological observations become available.This article is part of the Theo
      Murphy meeting issue 'Higgs cosmology'.

PMID- 29358353
TI  - Vacuum stability in the early universe and the backreaction of classical gravity.
AB  - In the case of a metastable electroweak vacuum, the quantum corrected effective
      potential plays a crucial role in the potential instability of the standard
      model. In the early universe, in particular during inflation and reheating, this
      instability can be triggered leading to catastrophic vacuum decay. We discuss how
      the large space-time curvature of the early universe can be incorporated in the
      calculation and in many cases significantly modify the flat space prediction. The
      two key new elements are the unavoidable generation of the non-minimal coupling
      between the Higgs field and the scalar curvature of gravity and a curvature
      induced contribution to the running of the constants. For the minimal set up of
      the standard model and a decoupled inflation sector we show how a metastable
      vacuum can lead to very tight bounds for the non-minimal coupling. We also
      discuss a novel and very much related dark matter generation mechanism.This
      article is part of the Theo Murphy meeting issue 'Higgs cosmology'.

PMID- 29358354
TI  - Is electroweak baryogenesis dead?
AB  - Electroweak baryogenesis is severely challenged in its traditional settings: the
      minimal supersymmetric standard model, and in more general two Higgs doublet
      models. Fine tuning of parameters is required, or large couplings leading to a
      Landau pole at scales just above the new physics introduced. The situation is
      somewhat better in models with a singlet scalar coupling to the Higgs so as to
      give a strongly first-order phase transition due to a tree-level barrier, but
      even in this case no UV complete models had been demonstrated to give successful
      baryogenesis. Here, we point out some directions that overcome this limitation,
      by introducing a new source of particle-antiparticle (CP) violation in the
      couplings of the singlet field. A model of electroweak baryogenesis requiring no
      fine tuning and consistent to scales far above 1 TeV is demonstrated, in which
      dark matter plays the leading role in creating a CP asymmetry that is the source
      of the baryon asymmetry.This article is part of the Theo Murphy meeting issue
      'Higgs cosmology'.

PMID- 29358355
TI  - Cosmological implications of Higgs near-criticality.
AB  - The Standard Model electroweak (EW) vacuum, in the absence of new physics below
      the Planck scale, lies very close to the boundary between stability and
      metastability, with the last option being the most probable. Several cosmological
      implications of this so-called 'near-criticality' are discussed. In the
      metastable vacuum case, the main challenges that the survival of the EW vacuum
      faces during the evolution of the Universe are analysed. In the stable vacuum
      case, the possibility of implementing Higgs inflation is critically examined.This
      article is part of the Theo Murphy meeting issue 'Higgs cosmology'.

PMID- 29358356
TI  - Signatures of Higgs dilaton and critical Higgs inflation.
AB  - We test the Higgs dilaton inflation model (HDM) using the latest cosmological
      datasets, including the cosmic microwave background temperature, polarization and
      lensing data from the Planck satellite (2015), the BICEP and Keck Array
      experiments, the type Ia supernovae from the JLA catalogue, the baryon acoustic
      oscillations from CMASS, LOWZ and 6dF, the weak lensing data from the CFHTLenS
      survey and the matter power spectrum measurements from the latest SDSS data
      release. We find that the values of all cosmological parameters allowed by the
      HDM are well within the Planck satellite (2015) constraints. In particular, we
      determine [Formula: see text], [Formula: see text], [Formula: see text],
      [Formula: see text] and [Formula: see text] (at 95.5% c.l.). We also place new
      stringent constraints on the couplings of the HDM, xichi <0.00328 and [Formula:
      see text] (at 95.5% c.l.). We find that the HDM is only slightly better than the
      w0wa CDM model, with [Formula: see text] Given that the HDM has two fewer
      parameters, we find Bayesian evidence favouring the HDM over the w0wa CDM model.
      We also study the critical Higgs inflation model, taking into account the running
      of both the self-coupling lambda(MU) and the non-minimal coupling to gravity
      xi(MU). We find peaks in the curvature power spectrum at scales corresponding to
      the critical value MU that re-enter during the radiation era and collapse to form
      a broad distribution of clustered primordial black holes, which could constitute
      today the main component of dark matter.This article is part of the Theo Murphy
      meeting issue 'Higgs cosmology'.

PMID- 29358357
TI  - Renormalization group flow of the Higgs potential.
AB  - We summarize results for local and global properties of the effective potential
      for the Higgs boson obtained from the functional renormalization group, which
      allows one to describe the effective potential as a function of both scalar field
      amplitude and renormalization group scale. This sheds light onto the limitations
      of standard estimates which rely on the identification of the two scales and
      helps in clarifying the origin of a possible property of meta-stability of the
      Higgs potential. We demonstrate that the inclusion of higher-dimensional
      operators induced by an underlying theory at a high scale (GUT or Planck scale)
      can relax the conventional lower bound on the Higgs mass derived from the
      criterion of absolute stability.This article is part of the Theo Murphy meeting
      issue 'Higgs cosmology'.

PMID- 29358358
TI  - Accretion of a symmetry-breaking scalar field by a Schwarzschild black hole.
AB  - We simulate the behaviour of a Higgs-like field in the vicinity of a
      Schwarzschild black hole using a highly accurate numerical framework. We consider
      both the limit of the zero-temperature Higgs potential and a toy model for the
      time-dependent evolution of the potential when immersed in a slowly cooling
      radiation bath. Through these numerical investigations, we aim to improve our
      understanding of the non-equilibrium dynamics of a symmetry-breaking field (such
      as the Higgs) in the vicinity of a compact object such as a black hole.
      Understanding this dynamics may suggest new approaches for studying properties of
      scalar fields using black holes as a laboratory.This article is part of the Theo
      Murphy meeting issue 'Higgs Cosmology'.

PMID- 29358359
TI  - The serendipity of electroweak baryogenesis.
AB  - The origin of the matter-antimatter asymmetry of the universe remains unexplained
      in the Standard Model (SM) of particle physics. The origin of the flavour
      structure is another major puzzle of the theory. In this article, we report on
      recent work attempting to link the two themes through the appealing framework of
      electroweak (EW) baryogenesis. We show that Yukawa couplings of SM fermions can
      be the source of CP violation for EW baryogenesis if they vary at the same time
      as the Higgs is acquiring its vacuum expectation value, offering new avenues for
      EW baryogenesis. The advantage of this approach is that it circumvents the usual
      severe bounds from electric dipole moments. These ideas apply if the mechanism
      explaining the flavour structure of the SM is connected to EW symmetry breaking,
      as motivated for instance in Randall-Sundrum or Composite Higgs models. We
      compute the resulting baryon asymmetry for different configurations of the Yukawa
      coupling variation across the bubble wall and show that it can naturally be of
      the right order.This article is part of the Theo Murphy meeting issue 'Higgs
      cosmology'.

PMID- 29358361
TI  - Transcranial Magnetic Stimulation over Left Inferior Frontal and Posterior
      Temporal Cortex Disrupts Gesture-Speech Integration.
AB  - Language and action naturally occur together in the form of cospeech gestures,
      and there is now convincing evidence that listeners display a strong tendency to
      integrate semantic information from both domains during comprehension. A
      contentious question, however, has been which brain areas are causally involved
      in this integration process. In previous neuroimaging studies, left inferior
      frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) have emerged as
      candidate areas; however, it is currently not clear whether these areas are
      causally or merely epiphenomenally involved in gesture-speech integration. In the
      present series of experiments, we directly tested for a potential critical role
      of IFG and pMTG by observing the effect of disrupting activity in these areas
      using transcranial magnetic stimulation in a mixed gender sample of healthy human
      volunteers. The outcome measure was performance on a Stroop-like gesture task
      (Kelly et al., 2010a), which provides a behavioral index of gesture-speech
      integration. Our results provide clear evidence that disrupting activity in IFG
      and pMTG selectively impairs gesture-speech integration, suggesting that both
      areas are causally involved in the process. These findings are consistent with
      the idea that these areas play a joint role in gesture-speech integration, with
      IFG regulating strategic semantic access via top-down signals acting upon
      temporal storage areas.SIGNIFICANCE STATEMENT Previous neuroimaging studies
      suggest an involvement of inferior frontal gyrus and posterior middle temporal
      gyrus in gesture-speech integration, but findings have been mixed and due to
      methodological constraints did not allow inferences of causality. By adopting a
      virtual lesion approach involving transcranial magnetic stimulation, the present
      study provides clear evidence that both areas are causally involved in combining
      semantic information arising from gesture and speech. These findings support the
      view that, rather than being separate entities, gesture and speech are part of an
      integrated multimodal language system, with inferior frontal gyrus and posterior
      middle temporal gyrus serving as critical nodes of the cortical network
      underpinning this system.

PMID- 29358362
TI  - Aging Affects Adaptation to Sound-Level Statistics in Human Auditory Cortex.
AB  - Optimal perception requires efficient and adaptive neural processing of sensory
      input. Neurons in nonhuman mammals adapt to the statistical properties of
      acoustic feature distributions such that they become sensitive to sounds that are
      most likely to occur in the environment. However, whether human auditory
      responses adapt to stimulus statistical distributions and how aging affects
      adaptation to stimulus statistics is unknown. We used MEG to study how exposure
      to different distributions of sound levels affects adaptation in auditory cortex
      of younger (mean: 25 years; n = 19) and older (mean: 64 years; n = 20) adults
      (male and female). Participants passively listened to two sound-level
      distributions with different modes (either 15 or 45 dB sensation level). In a
      control block with long interstimulus intervals, allowing neural populations to
      recover from adaptation, neural response magnitudes were similar between younger
      and older adults. Critically, both age groups demonstrated adaptation to sound
      level stimulus statistics, but adaptation was altered for older compared with
      younger people: in the older group, neural responses continued to be sensitive to
      sound level under conditions in which responses were fully adapted in the younger
      group. The lack of full adaptation to the statistics of the sensory environment
      may be a physiological mechanism underlying the known difficulty that older
      adults have with filtering out irrelevant sensory information.SIGNIFICANCE
      STATEMENT Behavior requires efficient processing of acoustic stimulation. Animal
      work suggests that neurons accomplish efficient processing by adjusting their
      response sensitivity depending on statistical properties of the acoustic
      environment. Little is known about the extent to which this adaptation to
      stimulus statistics generalizes to humans, particularly to older humans. We used
      MEG to investigate how aging influences adaptation to sound-level statistics.
      Listeners were presented with sounds drawn from sound-level distributions with
      different modes (15 vs 45 dB). Auditory cortex neurons adapted to sound-level
      statistics in younger and older adults, but adaptation was incomplete in older
      people. The data suggest that the aging auditory system does not fully capitalize
      on the statistics available in sound environments to tune the perceptual system
      dynamically.

PMID- 29358360
TI  - Functional Segmentation of the Anterior Limb of the Internal Capsule: Linking
      White Matter Abnormalities to Specific Connections.
AB  - The anterior limb of the internal capsule (ALIC) carries thalamic and brainstem
      fibers from prefrontal cortical regions that are associated with different
      aspects of emotion, motivation, cognition processing, and decision-making. This
      large fiber bundle is abnormal in several psychiatric illnesses and a major
      target for deep brain stimulation. Yet, we have very little information about
      where specific prefrontal fibers travel within the bundle. Using a combination of
      tracing studies and diffusion MRI in male nonhuman primates, as well as diffusion
      MRI in male and female human subjects, we segmented the human ALIC into five
      regions based on the positions of axons from different cortical regions within
      the capsule. Fractional anisotropy (FA) abnormalities in patients with bipolar
      disorder were detected when FA was averaged in the ALIC segment that carries
      ventrolateral prefrontal cortical connections. Together, the results set the
      stage for linking abnormalities within the ALIC to specific connections and
      demonstrate the utility of applying connectivity profiles of large white matter
      bundles based on animal anatomic studies to human connections and associating
      disease abnormalities in those pathways with specific connections. The ability to
      functionally segment large white matter bundles into their components begins a
      new era of refining how we think about white matter organization and use that
      information in understanding abnormalities.SIGNIFICANCE STATEMENT The anterior
      limb of the internal capsule (ALIC) connects prefrontal cortex with the thalamus
      and brainstem and is abnormal in psychiatric illnesses. However, we know little
      about the location of specific prefrontal fibers within the bundle. Using a
      combination of animal tracing studies and diffusion MRI in animals and human
      subjects, we segmented the human ALIC into five regions based on the positions of
      axons from different cortical regions. We then demonstrated that differences in
      FA values between bipolar disorder patients and healthy control subjects were
      specific to a given segment. Together, the results set the stage for linking
      abnormalities within the ALIC to specific connections and for refining how we
      think about white matter organization in general.

PMID- 29358363
TI  - Serotonin Disinhibits a Caenorhabditis elegans Sensory Neuron by Suppressing Ca2+
      Dependent Negative Feedback.
AB  - Neuromodulators, such as serotonin (5-HT), alter neuronal excitability and
      synaptic strengths, and define different behavioral states. Neuromodulator
      dependent changes in neuronal activity patterns are frequently measured using
      calcium reporters because calcium imaging can easily be performed on intact
      functioning nervous systems. With only 302 neurons, the nematode Caenorhabditis
      elegans provides a relatively simple, yet powerful, system to understand
      neuromodulation at the level of individual neurons. C. elegans hermaphrodites are
      repelled by 1-octanol, and the initiation of these aversive responses is
      potentiated by 5-HT. 5-HT acts on the ASH polymodal nociceptors that sense the 1
      octanol stimulus. Surprisingly, 5-HT suppresses ASH Ca2+ transients while
      simultaneously potentiating 1-octanol-dependent ASH depolarization. Here we
      further explore this seemingly inverse relationship. Our results show the
      following (1) 5-HT acts downstream of depolarization, through Galphaq-mediated
      signaling and calcineurin, to inhibit L-type voltage-gated Ca2+ channels; (2) the
      1-octanol-evoked Ca2+ transients in ASHs inhibit depolarization; and (3) the Ca2+
      activated K+ channel, SLO-1, acts downstream of 5-HT and is a critical regulator
      of ASH response dynamics. These findings define a Ca2+-dependent inhibitory
      feedback loop that can be modulated by 5-HT to increase neuronal excitability and
      regulate behavior, and highlight the possibility that neuromodulator-induced
      changes in the amplitudes of Ca2+ transients do not necessarily predict
      corresponding changes in depolarization.SIGNIFICANCE STATEMENT Neuromodulators,
      such as 5-HT, modify behavior by regulating excitability and synaptic efficiency
      in neurons. Neuromodulation is often studied using Ca2+ imaging, whereby
      neuromodulator-dependent changes in neuronal activity levels can be detected in
      intact, functioning circuits. Here we show that 5-HT reduces the amplitude of
      depolarization-dependent Ca2+ transients in a C. elegans nociceptive neuron,
      through Galphaq signaling and calcineurin but that Ca2+ itself inhibits
      depolarization, likely through Ca2+-activated K+ channels. The net effect of 5
      HT, therefore, is to increase neuronal excitability through disinhibition. These
      results establish a novel 5-HT signal transduction pathway, and demonstrate that
      neuromodulators can change Ca2+ signals and depolarization amplitudes in opposite
      directions, simultaneously, within a single neuron.

PMID- 29358364
TI  - Single-Cell Stimulation in Barrel Cortex Influences Psychophysical Detection
      Performance.
AB  - A single whisker stimulus elicits action potentials in a sparse subset of neurons
      in somatosensory cortex. The precise contribution of these neurons to the
      animal's perception of a whisker stimulus is unknown. Here we show that single
      cell stimulation in rat barrel cortex of both sexes influences the psychophysical
      detection of a near-threshold whisker stimulus in a cell type-dependent manner,
      without affecting false alarm rate. Counterintuitively, stimulation of single
      fast-spiking putative inhibitory neurons increased detection performance. Single
      cell stimulation of putative excitatory neurons failed to change detection
      performance, except for a small subset of deep-layer neurons that were highly
      sensitive to whisker stimulation and that had an unexpectedly strong impact on
      detection performance. These findings indicate that the perceptual impact of
      excitatory barrel cortical neurons relates to their firing response to whisker
      stimulation and that strong activity in a single highly sensitive neuron in
      barrel cortex can already enhance sensory detection. Our data suggest that
      sensory detection is based on a decoding mechanism that lends a disproportionally
      large weight to interneurons and to deep-layer neurons showing a strong response
      to sensory stimulation.SIGNIFICANCE STATEMENT Rat whisker somatosensory cortex
      contains a variety of neuronal cell types with distinct anatomical and
      physiological characteristics. How each of these different cell types contribute
      to the animal's perception of whisker stimuli is unknown. We explored this
      question by using a powerful electrophysiological stimulation technique that
      allowed us to target and stimulate single neurons with different sensory response
      types in whisker cortex. In awake, behaving animals, trained to detect whisker
      stimulation, only costimulation of single fast-spiking inhibitory neurons or
      single deep-layer excitatory neurons with strong responses to whisker stimulation
      enhanced detection performance. Our data demonstrate that single cortical neurons
      can have measurable impact on the detection of sensory stimuli and suggest a
      decoding mechanism based on select cell types.

PMID- 29358366
TI  - Margaret McCartney: Hiding and seeking doctors' conflicts of interest.

PMID- 29358367
TI  - GP who sexually assaulted patients is jailed for 12 years.

PMID- 29358365
TI  - Cortical Connections Position Primate Area 25 as a Keystone for Interoception,
      Emotion, and Memory.
AB  - The structural and functional integrity of subgenual cingulate area 25 (A25) is
      crucial for emotional expression and equilibrium. A25 has a key role in affective
      networks, and its disruption has been linked to mood disorders, but its cortical
      connections have yet to be systematically or fully studied. Using neural tracers
      in rhesus monkeys, we found that A25 was densely connected with other
      ventromedial and posterior orbitofrontal areas associated with emotions and
      homeostasis. A moderate pathway linked A25 with frontopolar area 10, an area
      associated with complex cognition, which may regulate emotions and dampen
      negative affect. Beyond the frontal lobe, A25 was connected with auditory
      association areas and memory-related medial temporal cortices, and with the
      interoceptive-related anterior insula. A25 mostly targeted the superficial
      cortical layers of other areas, where broadly dispersed terminations comingled
      with modulatory inhibitory or disinhibitory microsystems, suggesting a dominant
      excitatory effect. The architecture and connections suggest that A25 is the
      consummate feedback system in the PFC. Conversely, in the entorhinal cortex, A25
      pathways terminated in the middle-deep layers amid a strong local inhibitory
      microenvironment, suggesting gating of hippocampal output to other cortices and
      memory storage. The graded cortical architecture and associated laminar patterns
      of connections suggest how areas, layers, and functionally distinct classes of
      inhibitory neurons can be recruited dynamically to meet task demands. The
      complement of cortical connections of A25 with areas associated with memory,
      emotion, and somatic homeostasis provide the circuit basis to understand its
      vulnerability in psychiatric and neurologic disorders.SIGNIFICANCE STATEMENT
      Integrity of the prefrontal subgenual cingulate cortex is crucial for healthy
      emotional function. Subgenual area 25 (A25) is mostly linked with other
      prefrontal areas associated with emotion in a dense network positioned to recruit
      large fields of cortex. In healthy states, A25 is associated with internal
      states, autonomic function, and transient negative affect. Constant hyperactivity
      in A25 is a biomarker for depression in humans and may trigger extensive
      activation in its dominant connections with areas associated with emotions and
      internal balance. A pathway between A25 and frontopolar area 10 may provide a
      critical link to regulate emotions and dampen persistent negative affect, which
      may be explored for therapeutic intervention in depression.

PMID- 29358368
TI  - Antibody detection by agglutination-PCR (ADAP) enables early diagnosis of HIV
      infection by oral fluid analysis.
AB  - Oral fluid (OF) is a highly effective substrate for population-based HIV
      screening efforts, as it is noninfectious and significantly easier to collect
      than blood. However, anti-HIV antibodies are found at far lower concentrations in
      OF compared with blood, leading to poor sensitivity and a longer period of time
      from infection to detection threshold. Thus, despite its inherent advantages in
      sample collection, OF is not widely used for population screening. Here we report
      the development of an HIV OF assay based on Antibody Detection by Agglutination
      PCR (ADAP) technology. This assay is 1,000-10,000 times more analytically
      sensitive than clinical enzyme-linked immunoassays (EIAs), displaying both 100%
      clinical sensitivity and 100% specificity for detecting HIV antibodies within OF
      samples. We show that the enhanced analytical sensitivity enables this assay to
      correctly identify HIV-infected individuals otherwise missed by current OF
      assays. We envision that the attributes of this improved HIV OF assay can
      increase testing rates of at-risk individuals while enabling diagnosis and
      treatment at an earlier time point.

PMID- 29358370
TI  - Regulation of inflammatory responses by dynamic subcellular localization of RNA
      binding protein Arid5a.
AB  - Adenine-thymine (AT)-rich interactive domain 5a (Arid5a) is an RNA-binding
      protein found in the cytoplasm and nucleus of normally growing cells. Although
      Arid5a is known to play an important role in immune regulation, whether and how
      Arid5a subcellular localization impacts immune regulation has remained unclear.
      In this study, we generated Arid5a transgenic (TG) mice to address this question.
      While ectopic Arid5a overexpression did not affect expression of inflammatory
      cytokines under unstimulated conditions, significantly higher levels of
      inflammatory cytokines, such as IL-6, were produced in response to
      lipopolysaccharide (LPS) stimulation. Consistent with this, TG mice were more
      sensitive to LPS treatment than wild-type mice. We also found that Arid5a is
      imported into the nucleus via a classical importin-alpha/beta1-mediated pathway.
      On stimulation, nuclear Arid5a levels were decreased, while there was a
      concomitant increase in cytoplasmic Arid5a. Arid5a is associated with up
      frameshift protein 1, and its nuclear export is regulated by a nuclear export
      receptor, chromosomal region maintenance 1. Taken together, these data indicate
      that Arid5a is a dynamic protein that translocates to the cytoplasm from the
      nucleus so as to properly exert its dual function in mRNA stabilization and
      transcriptional regulation during inflammatory conditions.

PMID- 29358369
TI  - A neurochemical hypothesis for the origin of hominids.
AB  - It has always been difficult to account for the evolution of certain human
      characters such as language, empathy, and altruism via individual reproductive
      success. However, the striatum, a subcortical region originally thought to be
      exclusively motor, is now known to contribute to social behaviors and
      "personality styles" that may link such complexities with natural selection. We
      here report that the human striatum exhibits a unique neurochemical profile that
      differs dramatically from those of other primates. The human signature of
      elevated striatal dopamine, serotonin, and neuropeptide Y, coupled with lowered
      acetylcholine, systematically favors externally driven behavior and greatly
      amplifies sensitivity to social cues that promote social conformity, empathy, and
      altruism. We propose that selection induced an initial form of this profile in
      early hominids, which increased their affiliative behavior, and that this shift
      either preceded or accompanied the adoption of bipedality and elimination of the
      sectorial canine. We further hypothesize that these changes were critical for
      increased individual fitness and promoted the adoption of social monogamy, which
      progressively increased cooperation as well as a dependence on tradition-based
      cultural transmission. These eventually facilitated the acquisition of language
      by elevating the reproductive advantage afforded those most sensitive to social
      cues.

PMID- 29358371
TI  - Tactile distance illusions reflect a coherent stretch of tactile space.
AB  - Illusions of the perception of distance between two touches on the skin have been
      described since the classic work of Weber in the 19th century. The perceptual
      mechanisms underlying such spatial distortions, however, remain poorly
      understood. One potential interpretation is that the representational space of
      touch is related to the true structure of the skin by a geometrically simple
      stretch. If distortions of tactile distance perception reflect a simple stretch
      of tactile space, perceived distance should vary predictably as a function of the
      orientation of the stimulus on the skin, showing a sinusoidal pattern. Here, we
      tested this prediction by obtained judgments of perceived tactile distance for
      pairs of touches aligned with eight orientations on the skin. Across four
      experiments, the results were highly consistent with this prediction, showing no
      apparent deviation from a model of simple stretch of tactile space. Similar
      results were apparent on both the dorsum and palm of the hand, as well as the
      forehead. These results show that spatial distortions of touch are well
      characterized by a geometrically simple stretch of tactile space.

PMID- 29358372
TI  - Surface structure evolution in a homologous series of ionic liquids.
AB  - Interfaces of room temperature ionic liquids (RTILs) are important for both
      applications and basic science and are therefore intensely studied. However, the
      evolution of their interface structure with the cation's alkyl chain length
      [Formula: see text] from Coulomb to van der Waals interaction domination has not
      yet been studied for even a single broad homologous RTIL series. We present here
      such a study of the liquid-air interface for [Formula: see text], using angstrom
      resolution X-ray methods. For [Formula: see text], a typical "simple liquid"
      monotonic surface-normal electron density profile [Formula: see text] is
      obtained, like those of water and organic solvents. For [Formula: see text],
      increasingly more pronounced nanoscale self-segregation of the molecules' charged
      moieties and apolar chains yields surface layering with alternating regions of
      headgroups and chains. The layering decays into the bulk over a few, to a few
      tens, of nanometers. The layering periods and decay lengths, their linear
      [Formula: see text] dependence, and slopes are discussed within two models, one
      with partial-chain interdigitation and the other with liquid-like chains. No
      surface-parallel long-range order is found within the surface layer. For
      [Formula: see text], a different surface phase is observed above melting. Our
      results also impact general liquid-phase issues like supramolecular self
      aggregation and bulk-surface structure relations.

PMID- 29358373
TI  - Hsp90 chaperones hemoglobin maturation in erythroid and nonerythroid cells.
AB  - Maturation of adult (alpha2beta2) and fetal hemoglobin (alpha2gamma2) tetramers
      requires that heme be incorporated into each globin. While hemoglobin alpha (Hb
      alpha) relies on a specific erythroid chaperone (alpha Hb-stabilizing protein,
      AHSP), the other chaperones that may help mature the partner globins (Hb-gamma or
      Hb-beta) in erythroid cells, or may enable nonerythroid cells to express mature
      Hb, are unknown. We investigated a role for heat-shock protein 90 (hsp90) in Hb
      maturation in erythroid precursor cells that naturally express Hb-alpha with
      either Hb-gamma (K562 and HiDEP-1 cells) or Hb-beta (HUDEP-2) and in nonerythroid
      cell lines that either endogenously express Hb-alphabeta (RAW and A549) or that
      we transfected to express the globins. We found the following: (i) AHSP and hsp90
      associate with distinct globin partners in their immature heme-free states (AHSP
      with apo-Hbalpha, and hsp90 with apo-Hbbeta or Hb-gamma) and that hsp90 does not
      associate with mature Hb. (ii) Hsp90 stabilizes the apo-globins and helps to
      drive their heme insertion reactions, as judged by pharmacologic hsp90 inhibition
      or by coexpression of an ATP-ase defective hsp90. (iii) In nonerythroid cells,
      heme insertion into all globins became hsp90-dependent, which may explain how
      mixed Hb tetramers can mature in cells that do not express AHSP. Together, our
      findings uncover a process in which hsp90 first binds to immature, heme-free Hb
      gamma or Hb-beta, drives their heme insertion process, and then dissociates to
      allow their heterotetramer formation with Hb-alpha. Thus, in driving heme
      insertion, hsp90 works in concert with AHSP to generate functional Hb tetramers
      during erythropoiesis.

PMID- 29358374
TI  - Eocene greenhouse climate revealed by coupled clumped isotope-Mg/Ca thermometry.
AB  - Past greenhouse periods with elevated atmospheric CO2 were characterized by
      globally warmer sea-surface temperatures (SST). However, the extent to which the
      high latitudes warmed to a greater degree than the tropics (polar amplification)
      remains poorly constrained, in particular because there are only a few
      temperature reconstructions from the tropics. Consequently, the relationship
      between increased CO2, the degree of tropical warming, and the resulting
      latitudinal SST gradient is not well known. Here, we present coupled clumped
      isotope (Delta47)-Mg/Ca measurements of foraminifera from a set of globally
      distributed sites in the tropics and midlatitudes. Delta47 is insensitive to
      seawater chemistry and therefore provides a robust constraint on tropical SST.
      Crucially, coupling these data with Mg/Ca measurements allows the precise
      reconstruction of Mg/Casw throughout the Eocene, enabling the reinterpretation of
      all planktonic foraminifera Mg/Ca data. The combined dataset constrains the range
      in Eocene tropical SST to 30-36  degrees C (from sites in all basins). We compare
      these accurate tropical SST to deep-ocean temperatures, serving as a minimum
      constraint on high-latitude SST. This results in a robust conservative
      reconstruction of the early Eocene latitudinal gradient, which was reduced by at
      least 32 +/- 10% compared with present day, demonstrating greater polar
      amplification than captured by most climate models.

PMID- 29358375
TI  - Modular origins of biological electron transfer chains.
AB  - Oxidoreductases catalyze electron transfer reactions that ultimately provide the
      energy for life. A limited set of ancestral protein-metal modules are presumably
      the building blocks that evolved into this diverse protein family. However, the
      identity of these modules and their path to modern oxidoreductases is unknown.
      Using a comparative structural analysis approach, we identify a set of
      fundamental electron transfer modules that have evolved to form the extant
      oxidoreductases. Using transition metal-containing cofactors as fiducial markers,
      it is possible to cluster cofactor microenvironments into as few as four major
      modules: bacterial ferredoxin, cytochrome c, symerythrin, and plastocyanin-type
      folds. From structural alignments, it is challenging to ascertain whether modules
      evolved from a single common ancestor (homology) or arose by independent
      convergence on a limited set of structural forms (analogy). Additional insight
      into common origins is contained in the spatial adjacency network (SPAN), which
      is based on proximity of modules in oxidoreductases containing multiple cofactor
      electron transfer chains. Electron transfer chains within complex modern
      oxidoreductases likely evolved through repeated duplication and diversification
      of ancient modular units that arose in the Archean eon.

PMID- 29358376
TI  - High-resolution cryo-EM structures of actin-bound myosin states reveal the
      mechanism of myosin force sensing.
AB  - Myosins adjust their power outputs in response to mechanical loads in an isoform
      dependent manner, resulting in their ability to dynamically adapt to a range of
      motile challenges. Here, we reveal the structural basis for force-sensing based
      on near-atomic resolution structures of one rigor and two ADP-bound states of
      myosin-IB (myo1b) bound to actin, determined by cryo-electron microscopy. The two
      ADP-bound states are separated by a 25 degrees  rotation of the lever. The lever
      of the first ADP state is rotated toward the pointed end of the actin filament
      and forms a previously unidentified interface with the N-terminal subdomain,
      which constitutes the upper half of the nucleotide-binding cleft. This pointed
      end orientation of the lever blocks ADP release by preventing the N-terminal
      subdomain from the pivoting required to open the nucleotide binding site, thus
      revealing how myo1b is inhibited by mechanical loads that restrain lever
      rotation. The lever of the second ADP state adopts a rigor-like orientation,
      stabilized by class-specific elements of myo1b. We identify a role for this
      conformation as an intermediate in the ADP release pathway. Moreover, comparison
      of our structures with other myosins reveals structural diversity in the
      actomyosin binding site, and we reveal the high-resolution structure of actin
      bound phalloidin, a potent stabilizer of filamentous actin. These results provide
      a framework to understand the spectrum of force-sensing capacities among the
      myosin superfamily.

PMID- 29358377
TI  - Heritable aspects of biological motion perception and its covariation with
      autistic traits.
AB  - The ability to detect biological motion (BM) and decipher the meaning therein is
      essential to human survival and social interaction. However, at the individual
      level, we are not equally equipped with this ability. In particular, impaired BM
      perception and abnormal neural responses to BM have been observed in autism
      spectrum disorder (ASD), a highly heritable neurodevelopmental disorder
      characterized by devastating social deficits. Here, we examined the underlying
      sources of individual differences in two abilities fundamental to BM perception
      (i.e., the abilities to process local kinematic and global configurational
      information of BM) and explored whether BM perception shares a common genetic
      origin with autistic traits. Using the classical twin method, we found reliable
      genetic influences on BM perception and revealed a clear dissociation between its
      two components-whereas genes account for about 50% of the individual variation in
      local BM processing, global BM processing is largely shaped by environment.
      Critically, participants' sensitivity to local BM cues was negatively correlated
      with their autistic traits through the dimension of social communication, with
      the covariation largely mediated by shared genetic effects. These findings
      demonstrate that the ability to process BM, especially with regard to its
      inherent kinetics, is heritable. They also advance our understanding of the
      sources of the linkage between autistic symptoms and BM perception deficits,
      opening up the possibility of treating the ability to process local BM
      information as a distinct hallmark of social cognition.

PMID- 29358378
TI  - Redirection of lipid flux toward phospholipids in yeast increases fatty acid
      turnover and secretion.
AB  - Bio-based production of fatty acids and fatty acid-derived products can enable
      sustainable substitution of petroleum-derived fuels and chemicals. However,
      developing new microbial cell factories for producing high levels of fatty acids
      requires extensive engineering of lipid metabolism, a complex and tightly
      regulated metabolic network. Here we generated a Saccharomyces cerevisiae
      platform strain with a simplified lipid metabolism network with high-level
      production of free fatty acids (FFAs) due to redirected fatty acid metabolism and
      reduced feedback regulation. Deletion of the main fatty acid activation genes
      (the first step in beta-oxidation), main storage lipid formation genes, and
      phosphatidate phosphatase genes resulted in a constrained lipid metabolic network
      in which fatty acid flux was directed to a large extent toward phospholipids.
      This resulted in simultaneous increases of phospholipids by up to 2.8-fold and of
      FFAs by up to 40-fold compared with wild-type levels. Further deletion of
      phospholipase genes PLB1 and PLB2 resulted in a 46% decrease in FFA levels and
      105% increase in phospholipid levels, suggesting that phospholipid hydrolysis
      plays an important role in FFA production when phospholipid levels are increased.
      The multiple deletion mutant generated allowed for a study of fatty acid dynamics
      in lipid metabolism and represents a platform strain with interesting properties
      that provide insight into the future development of lipid-related cell factories.

PMID- 29358380
TI  - Aberration-corrected cryoimmersion light microscopy.
AB  - Cryogenic fluorescent light microscopy of flash-frozen cells stands out by
      artifact-free fixation and very little photobleaching of the fluorophores used.
      To attain the highest level of resolution, aberration-free immersion objectives
      with accurately matched immersion media are required, but both do not exist for
      imaging below the glass-transition temperature of water. Here, we resolve this
      challenge by combining a cryoimmersion medium, HFE-7200, which matches the
      refractive index of room-temperature water, with a technological concept in which
      the body of the objective and the front lens are not in thermal equilibrium. We
      implemented this concept by replacing the metallic front-lens mount of a standard
      bioimaging water immersion objective with an insulating ceramic mount heated
      around its perimeter. In this way, the objective metal housing can be maintained
      at room temperature, while creating a thermally shielded cold microenvironment
      around the sample and front lens. To demonstrate the range of potential
      applications, we show that our method can provide superior contrast in
      Escherichia coli and yeast cells expressing fluorescent proteins and resolve
      submicrometer structures in multicolor immunolabeled human bone osteosarcoma
      epithelial (U2OS) cells at [Formula: see text]C.

PMID- 29358381
TI  - Structural flexibility and protein adaptation to temperature: Molecular dynamics
      analysis of malate dehydrogenases of marine molluscs.
AB  - Orthologous proteins of species adapted to different temperatures exhibit
      differences in stability and function that are interpreted to reflect adaptive
      variation in structural "flexibility." However, quantifying flexibility and
      comparing flexibility across proteins has remained a challenge. To address this
      issue, we examined temperature effects on cytosolic malate dehydrogenase (cMDH)
      orthologs from differently thermally adapted congeners of five genera of marine
      molluscs whose field body temperatures span a range of ~60  degrees C. We
      describe consistent patterns of convergent evolution in adaptation of function
      [temperature effects on KM of cofactor (NADH)] and structural stability (rate of
      heat denaturation of activity). To determine how these differences depend on
      flexibilities of overall structure and of regions known to be important in
      binding and catalysis, we performed molecular dynamics simulation (MDS) analyses.
      MDS analyses revealed a significant negative correlation between adaptation
      temperature and heat-induced increase of backbone atom movements [root mean
      square deviation (rmsd) of main-chain atoms]. Root mean square fluctuations
      (RMSFs) of movement by individual amino acid residues varied across the sequence
      in a qualitatively similar pattern among orthologs. Regions of sequence involved
      in ligand binding and catalysis-termed mobile regions 1 and 2 (MR1 and MR2),
      respectively-showed the largest values for RMSF. Heat-induced changes in RMSF
      values across the sequence and, importantly, in MR1 and MR2 were greatest in cold
      adapted species. MDS methods are shown to provide powerful tools for examining
      adaptation of enzymes by providing a quantitative index of protein flexibility
      and identifying sequence regions where adaptive change in flexibility occurs.

PMID- 29358379
TI  - Context-dependent functions of angiopoietin 2 are determined by the endothelial
      phosphatase VEPTP.
AB  - The angiopoietin (ANGPT)-TIE2/TEK signaling pathway is essential for blood and
      lymphatic vascular homeostasis. ANGPT1 is a potent TIE2 activator, whereas ANGPT2
      functions as a context-dependent agonist/antagonist. In disease, ANGPT2-mediated
      inhibition of TIE2 in blood vessels is linked to vascular leak, inflammation, and
      metastasis. Using conditional knockout studies in mice, we show TIE2 is
      predominantly activated by ANGPT1 in the cardiovascular system and by ANGPT2 in
      the lymphatic vasculature. Mechanisms underlying opposing actions of ANGPT2 in
      blood vs. lymphatic endothelium are poorly understood. Here we show the
      endothelial-specific phosphatase VEPTP (vascular endothelial protein tyrosine
      phosphatase) determines TIE2 response to ANGPT2. VEPTP is absent from lymphatic
      endothelium in mouse in vivo, permitting ANGPT2/TIE2-mediated lymphangiogenesis.
      Inhibition of VEPTP converts ANGPT2 into a potent TIE2 activator in blood
      endothelium. Our data support a model whereby VEPTP functions as a rheostat to
      modulate ANGPT2 ligand effect on TIE2.

PMID- 29358382
TI  - Prediction of inherited genomic susceptibility to 20 common cancer types by a
      supervised machine-learning method.
AB  - Prevention and early intervention are the most effective ways of avoiding or
      minimizing psychological, physical, and financial suffering from cancer. However,
      such proactive action requires the ability to predict the individual's
      susceptibility to cancer with a measure of probability. Of the triad of cancer
      causing factors (inherited genomic susceptibility, environmental factors, and
      lifestyle factors), the inherited genomic component may be derivable from the
      recent public availability of a large body of whole-genome variation data.
      However, genome-wide association studies have so far showed limited success in
      predicting the inherited susceptibility to common cancers. We present here a
      multiple classification approach for predicting individuals' inherited genomic
      susceptibility to acquire the most likely phenotype among a panel of 20 major
      common cancer types plus 1 "healthy" type by application of a supervised machine
      learning method under competing conditions among the cohorts of the 21 types.
      This approach suggests that, depending on the phenotypes of 5,919 individuals of
      "white" ethnic population in this study, (i) the portion of the cohort of a
      cancer type who acquired the observed type due to mostly inherited genomic
      susceptibility factors ranges from about 33 to 88% (or its corollary: the portion
      due to mostly environmental and lifestyle factors ranges from 12 to 67%), and
      (ii) on an individual level, the method also predicts individuals' inherited
      genomic susceptibility to acquire the other types ranked with associated
      probabilities. These probabilities may provide practical information for
      individuals, heath professionals, and health policymakers related to prevention
      and/or early intervention of cancer.

PMID- 29358383
TI  - Urban flux measurements reveal a large pool of oxygenated volatile organic
      compound emissions.
AB  - Atmospheric chemistry is fueled by a large annual influx of nonmethane volatile
      organic compounds (NMVOC). These compounds influence ozone formation, lead to
      secondary organic aerosol production, and play a significant role for the
      oxidizing capacity of the atmosphere. The anthropogenic NMVOC budget is
      considerably uncertain due to the diversity of urban emission sources. Here, we
      present comprehensive observations of urban NMVOC eddy covariance fluxes using a
      newly designed proton-transfer-reaction quadrupole interface time-of-flight mass
      spectrometer. We found emission fluxes of a surprisingly large pool of oxygenated
      NMVOCs (OVOCs) with an appreciable fraction of higher oxidized OVOCs that cannot
      be explained by known fast photochemical turnaround or current primary emission
      estimates. Measured OVOC/NMVOC bulk flux ratios are two to four times higher than
      inferred from aggregated anthropogenic emission inventories. Extrapolating these
      results would double the global anthropogenic NMVOC flux. In view of globally
      accelerating urbanization, our study highlights the need to reevaluate the
      influence of anthropogenic NMVOC on atmospheric chemistry, human health, and the
      climate system.

PMID- 29358384
TI  - Humidity determines snowpack ablation under a warming climate.
AB  - Climate change is altering historical patterns of snow accumulation and melt,
      threatening societal frameworks for water supply. However, decreases in spring
      snow water equivalent (SWE) and changes in snowmelt are not ubiquitous despite
      widespread warming in the western United States, highlighting the importance of
      latent and radiant energy fluxes in snow ablation. Here we demonstrate how
      atmospheric humidity and solar radiation interact with warming temperature to
      control snowpack ablation at 462 sites spanning a gradient in mean winter
      temperature from -8.9 to +2.9  degrees C. The most widespread response to warming
      was an increase in episodic, midwinter ablation events. Under humid conditions
      these ablation events were dominated by melt, averaging 21% (202 mm/year) of SWE.
      Winter ablation under dry atmospheric conditions at similar temperatures was
      smaller, averaging 12% (58 mm/year) of SWE and likely dominated by sublimation
      fluxes. These contrasting patterns result from the critical role that atmospheric
      humidity plays in local energy balance, with latent and longwave radiant fluxes
      cooling the snowpack under dry conditions and warming it under humid conditions.
      Similarly, spring melt rates were faster under humid conditions, yet the second
      most common trend was a reduction in spring melt rates associated with earlier
      initiation when solar radiation inputs are smaller. Our analyses demonstrate that
      regional differences in atmospheric humidity are a major cause of the spatial
      variability in snowpack response to warming. Better constraints on humidity will
      be critical to predicting both the amount and timing of surface water supplies
      under climate change.

PMID- 29358386
TI  - Profile of Steve Granick.

PMID- 29358385
TI  - Shape-directed dynamics of active colloids powered by induced-charge
      electrophoresis.
AB  - The symmetry and shape of colloidal particles can direct complex particle motions
      through fluid environments powered by simple energy inputs. The ability to
      rationally design or "program" the dynamics of such active colloids is an
      important step toward the realization of colloidal machines, in which components
      assemble spontaneously in space and time to perform dynamic (dissipative)
      functions such as actuation and transport. Here, we systematically investigate
      the dynamics of polarizable particles of different shapes moving in an
      oscillating electric field via induced-charge electrophoresis (ICEP). We consider
      particles from each point group in three dimensions (3D) and identify the
      different rotational and translational motions allowed by symmetry. We describe
      how the 3D shape of rigid particles can be tailored to achieve desired dynamics
      including oscillatory motions, helical trajectories, and complex periodic orbits.
      The methodology we develop is generally applicable to the design of shape
      directed particle motions powered by other energy inputs.

PMID- 29358387
TI  - Precipitation formation from orographic cloud seeding.
AB  - Throughout the western United States and other semiarid mountainous regions
      across the globe, water supplies are fed primarily through the melting of
      snowpack. Growing populations place higher demands on water, while warmer winters
      and earlier springs reduce its supply. Water managers are tantalized by the
      prospect of cloud seeding as a way to increase winter snowfall, thereby shifting
      the balance between water supply and demand. Little direct scientific evidence
      exists that confirms even the basic physical hypothesis upon which cloud seeding
      relies. The intent of glaciogenic seeding of orographic clouds is to introduce
      aerosol into a cloud to alter the natural development of cloud particles and
      enhance wintertime precipitation in a targeted region. The hypothesized chain of
      events begins with the introduction of silver iodide aerosol into cloud regions
      containing supercooled liquid water, leading to the nucleation of ice crystals,
      followed by ice particle growth to sizes sufficiently large such that snow falls
      to the ground. Despite numerous experiments spanning several decades, no direct
      observations of this process exist. Here, measurements from radars and aircraft
      mounted cloud physics probes are presented that together show the initiation,
      growth, and fallout to the mountain surface of ice crystals resulting from
      glaciogenic seeding. These data, by themselves, do not address the question of
      cloud seeding efficacy, but rather form a critical set of observations necessary
      for such investigations. These observations are unambiguous and provide details
      of the physical chain of events following the introduction of glaciogenic cloud
      seeding aerosol into supercooled liquid orographic clouds.

PMID- 29358388
TI  - Early hominids may have been weed species.
AB  - Panid, gorillid, and hominid social structures appear to have diverged as
      dramatically as did their locomotor patterns as they emerged from a late Miocene
      last common ancestor (LCA). Despite their elimination of the sectorial canine
      complex and adoption of bipedality with its attendant removal of their ready
      access to the arboreal canopy, Australopithecus was able to easily invade novel
      habitats after florescence from its likely ancestral genus, Ardipithecus sp.
      Other hominoids, unable to sustain sufficient population growth, began an
      inexorable decline, culminating in their restriction to modern refugia. Success
      similar to that of earliest hominids also characterizes several species of
      macaques, often termed "weed species." We here review their most salient
      demographic features and find that a key element is irregularly elevated female
      survival. It is reasonable to conclude that a similar feature characterized early
      hominids, most likely made possible by the adoption of social monogamy. Reduced
      female mortality is a more probable key to early hominid success than a reduction
      in birth space, which would have been physiologically more difficult.

PMID- 29358389
TI  - Climate vulnerability and resilience in the most valuable North American fishery.
AB  - Managing natural resources in an era of increasing climate impacts requires
      accounting for the synergistic effects of climate, ecosystem changes, and
      harvesting on resource productivity. Coincident with recent exceptional warming
      of the northwest Atlantic Ocean and removal of large predatory fish, the American
      lobster has become the most valuable fishery resource in North America. Using a
      model that links ocean temperature, predator density, and fishing to population
      productivity, we show that harvester-driven conservation efforts to protect large
      lobsters prepared the Gulf of Maine lobster fishery to capitalize on favorable
      ecosystem conditions, resulting in the record-breaking landings recently observed
      in the region. In contrast, in the warmer southern New England region, the
      absence of similar conservation efforts precipitated warming-induced recruitment
      failure that led to the collapse of the fishery. Population projections under
      expected warming suggest that the American lobster fishery is vulnerable to
      future temperature increases, but continued efforts to preserve the stock's
      reproductive potential can dampen the negative impacts of warming. This study
      demonstrates that, even though global climate change is severely impacting marine
      ecosystems, widely adopted, proactive conservation measures can increase the
      resilience of commercial fisheries to climate change.

PMID- 29358390
TI  - Frequency modulation of neural oscillations according to visual task demands.
AB  - Temporal integration in visual perception is thought to occur within cycles of
      occipital alpha-band (8-12 Hz) oscillations. Successive stimuli may be integrated
      when they fall within the same alpha cycle and segregated for different alpha
      cycles. Consequently, the speed of alpha oscillations correlates with the
      temporal resolution of perception, such that lower alpha frequencies provide
      longer time windows for perceptual integration and higher alpha frequencies
      correspond to faster sampling and segregation. Can the brain's rhythmic activity
      be dynamically controlled to adjust its processing speed according to different
      visual task demands? We recorded magnetoencephalography (MEG) while participants
      switched between task instructions for temporal integration and segregation,
      holding stimuli and task difficulty constant. We found that the peak frequency of
      alpha oscillations decreased when visual task demands required temporal
      integration compared with segregation. Alpha frequency was strategically
      modulated immediately before and during stimulus processing, suggesting a
      preparatory top-down source of modulation. Its neural generators were located in
      occipital and inferotemporal cortex. The frequency modulation was specific to
      alpha oscillations and did not occur in the delta (1-3 Hz), theta (3-7 Hz), beta
      (15-30 Hz), or gamma (30-50 Hz) frequency range. These results show that alpha
      frequency is under top-down control to increase or decrease the temporal
      resolution of visual perception.

PMID- 29358391
TI  - Evolutionary history of carbon monoxide dehydrogenase/acetyl-CoA synthase, one of
      the oldest enzymatic complexes.
AB  - Carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) is a five-subunit
      enzyme complex responsible for the carbonyl branch of the Wood-Ljungdahl (WL)
      pathway, considered one of the most ancient metabolisms for anaerobic carbon
      fixation, but its origin and evolutionary history have been unclear. While
      traditionally associated with methanogens and acetogens, the presence of CODH/ACS
      homologs has been reported in a large number of uncultured anaerobic lineages.
      Here, we have carried out an exhaustive phylogenomic study of CODH/ACS in over
      6,400 archaeal and bacterial genomes. The identification of complete and likely
      functional CODH/ACS complexes in these genomes significantly expands its
      distribution in microbial lineages. The CODH/ACS complex displays astounding
      conservation and vertical inheritance over geological times. Rare intradomain and
      interdomain transfer events might tie into important functional transitions,
      including the acquisition of CODH/ACS in some archaeal methanogens not known to
      fix carbon, the tinkering of the complex in a clade of model bacterial acetogens,
      or emergence of archaeal-bacterial hybrid complexes. Once these transfers were
      clearly identified, our results allowed us to infer the presence of a CODH/ACS
      complex with at least four subunits in the last universal common ancestor (LUCA).
      Different scenarios on the possible role of ancestral CODH/ACS are discussed.
      Despite common assumptions, all are equally compatible with an autotrophic,
      mixotrophic, or heterotrophic LUCA. Functional characterization of CODH/ACS from
      a larger spectrum of bacterial and archaeal lineages and detailed evolutionary
      analysis of the WL methyl branch will help resolve this issue.

PMID- 29358392
TI  - IL-1beta enables CNS access to CCR2hi monocytes and the generation of pathogenic
      cells through GM-CSF released by CNS endothelial cells.
AB  - Molecular interventions that limit pathogenic CNS inflammation are used to treat
      autoimmune conditions such as multiple sclerosis (MS). Remarkably, IL-1beta
      knockout mice are highly resistant to experimental autoimmune encephalomyelitis
      (EAE), an animal model of MS. Here, we show that interfering with the IL-1beta/IL
      1R1 axis severely impairs the transmigration of myeloid cells across central
      nervous system (CNS) endothelial cells (ECs). Notably, we report that IL-1beta
      expression by inflammatory CCR2hi monocytes favors their entry into the spinal
      cord before EAE onset. Following activation with IL-1beta, CNS ECs release GM
      CSF, which in turn converts monocytes into antigen-presenting cells (APCs).
      Accordingly, spinal cord-infiltrated monocyte-derived APCs are associated with
      dividing CD4+ T cells. Factors released from the interaction between IL-1beta
      competent myeloid cells and CD4+ T cells are highly toxic to neurons. Together,
      our results suggest that IL-1beta signaling is an entry point for targeting both
      the initiation and exacerbation of neuroinflammation.

PMID- 29358393
TI  - Increased thermogenesis by a noncanonical pathway in ANGPTL3/8-deficient mice.
AB  - Dietary triglyceride (TG) is the most efficient energy substrate. It is processed
      and stored at substantially lower metabolic cost than is protein or carbohydrate.
      In fed animals, circulating TGs are preferentially routed for storage to white
      adipose tissue (WAT) by angiopoietin-like proteins 3 (A3) and 8 (A8). Here, we
      show that mice lacking A3 and A8 (A3-/-A8-/- mice) have decreased fat mass and a
      striking increase in temperature (+1  degrees C) in the fed (but not fasted)
      state, without alterations in food intake or physical activity. Subcutaneous WAT
      (WAT-SQ) from these animals had morphologic and metabolic changes characteristic
      of beiging. O2 consumption rates (OCRs) and expression of genes involved in both
      fatty acid synthesis and fatty acid oxidation were increased in WAT-SQ of A3-/-A8
      /- mice, but not in their epididymal or brown adipose tissue (BAT). The
      hyperthermic response to feeding was blocked by maintaining A3-/-A8-/- mice at
      thermoneutrality or by treating with a beta3-adrenergic receptor (AR) antagonist.
      To determine if sympathetic stimulation was sufficient to increase body
      temperature in A3-/-A8-/- mice, WT and A3-/-A8-/- animals were maintained at
      thermoneutrality and then treated with a beta3-AR agonist; treatment induced
      hyperthermia in A3-/-A8-/- , but not WT, mice. Antibody-mediated inactivation of
      both circulating A3 and A8 induced hyperthermia in WT mice. Together, these data
      indicate that A3 and A8 are essential for efficient storage of dietary TG and
      that disruption of these genes increases feeding-induced thermogenesis and energy
      utilization.

PMID- 29358394
TI  - Global models underestimate large decadal declining and rising water storage
      trends relative to GRACE satellite data.
AB  - Assessing reliability of global models is critical because of increasing reliance
      on these models to address past and projected future climate and human stresses
      on global water resources. Here, we evaluate model reliability based on a
      comprehensive comparison of decadal trends (2002-2014) in land water storage from
      seven global models (WGHM, PCR-GLOBWB, GLDAS NOAH, MOSAIC, VIC, CLM, and CLSM) to
      trends from three Gravity Recovery and Climate Experiment (GRACE) satellite
      solutions in 186 river basins (~60% of global land area). Medians of modeled
      basin water storage trends greatly underestimate GRACE-derived large decreasing
      (<=-0.5 km3/y) and increasing (>=0.5 km3/y) trends. Decreasing trends from GRACE
      are mostly related to human use (irrigation) and climate variations, whereas
      increasing trends reflect climate variations. For example, in the Amazon, GRACE
      estimates a large increasing trend of ~43 km3/y, whereas most models estimate
      decreasing trends (-71 to 11 km3/y). Land water storage trends, summed over all
      basins, are positive for GRACE (~71-82 km3/y) but negative for models (-450 to 
      12 km3/y), contributing opposing trends to global mean sea level change. Impacts
      of climate forcing on decadal land water storage trends exceed those of modeled
      human intervention by about a factor of 2. The model-GRACE comparison highlights
      potential areas of future model development, particularly simulated water
      storage. The inability of models to capture large decadal water storage trends
      based on GRACE indicates that model projections of climate and human-induced
      water storage changes may be underestimated.

PMID- 29358395
TI  - Genetic and epigenetic alterations in normal tissues have differential impacts on
      cancer risk among tissues.
AB  - Genetic and epigenetic alterations are both involved in carcinogenesis, and their
      low-level accumulation in normal tissues constitutes cancer risk. However, their
      relative importance has never been examined, as measurement of low-level
      mutations has been difficult. Here, we measured low-level accumulations of
      genetic and epigenetic alterations in normal tissues with low, intermediate, and
      high cancer risk and analyzed their relative effects on cancer risk in the
      esophagus and stomach. Accumulation of genetic alterations, estimated as a
      frequency of rare base substitution mutations, significantly increased according
      to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation
      patterns reflected the exposure to lifestyle risk factors. In contrast, the
      accumulation of epigenetic alterations, measured as DNA methylation levels of
      marker genes, significantly increased according to cancer risk in both tissues.
      Patients with cancer (high-risk individuals) were precisely discriminated from
      healthy individuals with exposure to risk factors (intermediate-risk individuals)
      by a combination of alterations in the esophagus (odds ratio, 18.2; 95%
      confidence interval, 3.69-89.9) and by only epigenetic alterations in the stomach
      (odds ratio, 7.67; 95% confidence interval, 2.52-23.3). The relative importance
      of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and
      2.31 in the stomach. The differential impacts among tissues will be critically
      important for effective cancer prevention and precision cancer risk diagnosis.

PMID- 29358397
TI  - Potential for western US seasonal snowpack prediction.
AB  - Western US snowpack-snow that accumulates on the ground in the mountains-plays a
      critical role in regional hydroclimate and water supply, with 80% of snowmelt
      runoff being used for agriculture. While climate projections provide estimates of
      snowpack loss by the end of the century and weather forecasts provide predictions
      of weather conditions out to 2 weeks, less progress has been made for snow
      predictions at seasonal timescales (months to 2 years), crucial for regional
      agricultural decisions (e.g., plant choice and quantity). Seasonal predictions
      with climate models first took the form of El Nino predictions 3 decades ago,
      with hydroclimate predictions emerging more recently. While the field has been
      focused on single-season predictions (3 months or less), we are now poised to
      advance our predictions beyond this timeframe. Utilizing observations, climate
      indices, and a suite of global climate models, we demonstrate the feasibility of
      seasonal snowpack predictions and quantify the limits of predictive skill 8
      months in advance. This physically based dynamic system outperforms observation
      based statistical predictions made on July 1 for March snowpack everywhere except
      the southern Sierra Nevada, a region where prediction skill is nonexistent for
      every predictor presently tested. Additionally, in the absence of externally
      forced negative trends in snowpack, narrow maritime mountain ranges with high
      hydroclimate variability pose a challenge for seasonal prediction in our present
      system; natural snowpack variability may inherently be unpredictable at this
      timescale. This work highlights present prediction system successes and gives
      cause for optimism for developing seasonal predictions for societal needs.

PMID- 29358396
TI  - Centipedes subdue giant prey by blocking KCNQ channels.
AB  - Centipedes can subdue giant prey by using venom, which is metabolically expensive
      to synthesize and thus used frugally through efficiently disrupting essential
      physiological systems. Here, we show that a centipede (Scolopendra subspinipes
      mutilans, ~3 g) can subdue a mouse (~45 g) within 30 seconds. We found that this
      observation is largely due to a peptide toxin in the venom, SsTx, and further
      established that SsTx blocks KCNQ potassium channels to exert the lethal
      toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the
      toxicity of a centipede's venom. The study indicates that centipedes' venom has
      evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and
      nervous systems by targeting the broadly distributed KCNQ channels, thus
      providing a therapeutic strategy for centipede envenomation.

PMID- 29358398
TI  - Nonsense-mediated mRNA decay factors cure most [PSI+] prion variants.
AB  - The yeast prion [PSI+] is a self-propagating amyloid of Sup35p with a folded in
      register parallel beta-sheet architecture. In a genetic screen for antiprion
      genes, using the yeast knockout collection, UPF1/NAM7 and UPF3, encoding nonsense
      mediated mRNA decay (NMD) factors, were frequently detected. Almost all [PSI+]
      variants arising in the absence of Upf proteins were eliminated by restored
      normal levels of these proteins, and [PSI+] arises more frequently in upf
      mutants. Upf1p, complexed with Upf2p and Upf3p, is a multifunctional protein with
      helicase, ATP-binding, and RNA-binding activities promoting efficient translation
      termination and degradation of mRNAs with premature nonsense codons. We find that
      the curing ability of Upf proteins is uncorrelated with these previously reported
      functions but does depend on their interaction with Sup35p and formation of the
      Upf1p-Upf2p-Upf3p complex (i.e., the Upf complex). Indeed, Sup35p amyloid
      formation in vitro is inhibited by substoichiometric Upf1p. Inhibition of [PSI+]
      prion generation and propagation by Upf proteins may be due to the monomeric Upf
      proteins and the Upf complex competing with Sup35p amyloid fibers for available
      Sup35p monomers. Alternatively, the association of the Upf complex with amyloid
      filaments may block the addition of new monomers. Our results suggest that
      maintenance of normal protein-protein interactions prevents prion formation and
      can even reverse the process.

PMID- 29358399
TI  - Tau induces blood vessel abnormalities and angiogenesis-related gene expression
      in P301L transgenic mice and human Alzheimer's disease.
AB  - Mixed pathology, with both Alzheimer's disease and vascular abnormalities, is the
      most common cause of clinical dementia in the elderly. While usually thought to
      be concurrent diseases, the fact that changes in cerebral blood flow are a
      prominent early and persistent alteration in Alzheimer's disease raises the
      possibility that vascular alterations and Alzheimer pathology are more directly
      linked. Here, we report that aged tau-overexpressing mice develop changes to
      blood vessels including abnormal, spiraling morphologies; reduced blood vessel
      diameters; and increased overall blood vessel density in cortex. Blood flow in
      these vessels was altered, with periods of obstructed flow rarely observed in
      normal capillaries. These changes were accompanied by cortical atrophy as well as
      increased expression of angiogenesis-related genes such as Vegfa, Serpine1, and
      Plau in CD31-positive endothelial cells. Interestingly, mice overexpressing
      nonmutant forms of tau in the absence of frank neurodegeneration also
      demonstrated similar changes. Furthermore, many of the genes we observe in mice
      are also altered in human RNA datasets from Alzheimer patients, particularly in
      brain regions classically associated with tau pathology such as the temporal lobe
      and limbic system regions. Together these data indicate that tau pathological
      changes in neurons can impact brain endothelial cell biology, altering the
      integrity of the brain's microvasculature.

PMID- 29358400
TI  - Methyltransferases of gentamicin biosynthesis.
AB  - Gentamicin C complex from Micromonospora echinospora remains a globally important
      antibiotic, and there is revived interest in the semisynthesis of analogs that
      might show improved therapeutic properties. The complex consists of five
      components differing in their methylation pattern at one or more sites in the
      molecule. We show here, using specific gene deletion and chemical
      complementation, that the gentamicin pathway up to the branch point is defined by
      the selectivity of the methyltransferases GenN, GenD1, and GenK. Unexpectedly,
      they comprise a methylation network in which early intermediates are ectopically
      modified. Using whole-genome sequence, we have also discovered the terminal 6'-N
      methyltransfer required to produce gentamicin C2b from C1a or gentamicin C1 from
      C2, an example of an essential biosynthetic enzyme being located not in the
      biosynthetic gene cluster but far removed on the chromosome. These findings fully
      account for the methylation pattern in gentamicins and open the way to production
      of individual gentamicins by fermentation, as starting materials for
      semisynthesis.

PMID- 29358402
TI  - Correction for Droog et al., Estrogen receptor alpha wields treatment-specific
      enhancers between morphologically similar endometrial tumors.

PMID- 29358401
TI  - Establishment of the early cilia preassembly protein complex during motile
      ciliogenesis.
AB  - Motile cilia are characterized by dynein motor units, which preassemble in the
      cytoplasm before trafficking into the cilia. Proteins required for dynein
      preassembly were discovered by finding human mutations that result in absent
      ciliary motors, but little is known about their expression, function, or
      interactions. By monitoring ciliogenesis in primary airway epithelial cells and
      MCIDAS-regulated induced pluripotent stem cells, we uncovered two phases of
      expression of preassembly proteins. An early phase, composed of HEATR2, SPAG1,
      and DNAAF2, preceded other preassembly proteins and was independent of MCIDAS
      regulation. The early preassembly proteins colocalized within perinuclear foci
      that also contained dynein arm proteins. These proteins also interacted based on
      immunoprecipitation and Forster resonance energy transfer (FRET) studies. FRET
      analysis of HEAT domain deletions and human mutations showed that HEATR2
      interacted with itself and SPAG1 at multiple HEAT domains, while DNAAF2
      interacted with SPAG1. Human mutations in HEATR2 did not affect this interaction,
      but triggered the formation of p62/Sequestosome-1-positive aggregates containing
      the early preassembly proteins, suggesting that degradation of an early
      preassembly complex is responsible for disease and pointing to key regions
      required for HEATR2 scaffold stability. We speculate that HEATR2 is an early
      scaffold for the initiation of dynein complex assembly in motile cilia.

PMID- 29358403
TI  - Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model
      of Alzheimer's disease.
AB  - Neuronal hyperactivity is the emerging functional hallmark of Alzheimer's disease
      (AD) in both humans and different mouse models, mediating an impairment of memory
      and cognition. The mechanisms underlying neuronal hyperactivity remain, however,
      elusive. In vivo Ca2+ imaging of somatic, dendritic, and axonal activity patterns
      of cortical neurons revealed that both healthy aging and AD-related mutations
      augment neuronal hyperactivity. The AD-related enhancement occurred even without
      amyloid deposition and neuroinflammation, mainly due to presenilin-mediated
      dysfunction of intracellular Ca2+ stores in presynaptic boutons, likely causing
      more frequent activation of synaptic NMDA receptors. In mutant but not wild-type
      mice, store emptying reduced both the frequency and amplitude of presynaptic Ca2+
      transients and, most importantly, normalized neuronal network activity.
      Postsynaptically, the store dysfunction was minor and largely restricted to
      hyperactive cells. These findings identify presynaptic Ca2+ stores as a key
      element controlling AD-related neuronal hyperactivity and as a target for disease
      modifying treatments.

PMID- 29358404
TI  - Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune
      clusters of the bone marrow.
AB  - The bone marrow maintains memory CD4 T cells, which provide memory to systemic
      antigens. Here we demonstrate that memory CD4 T cells are reactivated by antigen
      in the bone marrow. In a secondary immune response, antigen-specific T cells of
      the bone marrow mobilize and aggregate in immune clusters together with MHC class
      II-expressing cells, mostly B lymphocytes. They proliferate vigorously and
      express effector cytokines, but they do not develop into follicular T-helper
      cells. Neither do the B lymphocytes develop into germinal center B cells in the
      bone marrow. Within 10 days, the immune clusters disappear again. Within 30 days,
      the expanded antigen-specific memory CD4 T cells return to memory niches and are
      maintained again individually as resting cells. Thus, in secondary immune
      responses in the bone marrow T-cell memory is amplified, while in germinal center
      reactions of secondary lymphoid organs humoral memory is adapted by affinity
      maturation.

PMID- 29358405
TI  - Assembly and ecological function of the root microbiome across angiosperm plant
      species.
AB  - Across plants and animals, host-associated microbial communities play fundamental
      roles in host nutrition, development, and immunity. The factors that shape host
      microbiome interactions are poorly understood, yet essential for understanding
      the evolution and ecology of these symbioses. Plant roots assemble two distinct
      microbial compartments from surrounding soil: the rhizosphere (microbes
      surrounding roots) and the endosphere (microbes within roots). Root-associated
      microbes were key for the evolution of land plants and underlie fundamental
      ecosystem processes. However, it is largely unknown how plant evolution has
      shaped root microbial communities, and in turn, how these microbes affect plant
      ecology, such as the ability to mitigate biotic and abiotic stressors. Here we
      show that variation among 30 angiosperm species, which have diverged for up to
      140 million years, affects root bacterial diversity and composition. Greater
      similarity in root microbiomes between hosts leads to negative effects on plant
      performance through soil feedback, with specific microbial taxa in the endosphere
      and rhizosphere potentially affecting competitive interactions among plant
      species. Drought also shifts the composition of root microbiomes, most notably by
      increasing the relative abundance of the Actinobacteria. However, this drought
      response varies across host plant species, and host-specific changes in the
      relative abundance of endosphere Streptomyces are associated with host drought
      tolerance. Our results emphasize the causes of variation in root microbiomes and
      their ecological importance for plant performance in response to biotic and
      abiotic stressors.

PMID- 29358406
TI  - Molecular clutch drives cell response to surface viscosity.
AB  - Cell response to matrix rigidity has been explained by the mechanical properties
      of the actin-talin-integrin-fibronectin clutch. Here the molecular clutch model
      is extended to account for cell interactions with purely viscous surfaces (i.e.,
      without an elastic component). Supported lipid bilayers present an idealized and
      controllable system through which to study this concept. Using lipids of
      different diffusion coefficients, the mobility (i.e., surface viscosity) of the
      presented ligands (in this case RGD) was altered by an order of magnitude. Cell
      size and cytoskeletal organization were proportional to viscosity. Furthermore,
      there was a higher number of focal adhesions and a higher phosphorylation of FAK
      on less-mobile (more-viscous) surfaces. Actin retrograde flow, an indicator of
      the force exerted on surfaces, was also seen to be faster on more mobile
      surfaces. This has consequential effects on downstream molecules; the
      mechanosensitive YAP protein localized to the nucleus more on less-mobile (more
      viscous) surfaces and differentiation of myoblast cells was enhanced on higher
      viscosity. This behavior was explained within the framework of the molecular
      clutch model, with lower viscosity leading to a low force loading rate,
      preventing the exposure of mechanosensitive proteins, and with a higher viscosity
      causing a higher force loading rate exposing these sites, activating downstream
      pathways. Consequently, the understanding of how viscosity (regardless of matrix
      stiffness) influences cell response adds a further tool to engineer materials
      that control cell behavior.

PMID- 29358408
TI  - Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the
      whole population of virus-induced leukemic cells.
AB  - Viruses causing chronic infection artfully manipulate infected cells to enable
      viral persistence in vivo under the pressure of immunity. Human T-cell leukemia
      virus type 1 (HTLV-1) establishes persistent infection mainly in CD4+ T cells in
      vivo and induces leukemia in this subset. HTLV-1-encoded Tax is a critical
      transactivator of viral replication and a potent oncoprotein, but its
      significance in pathogenesis remains obscure due to its very low level of
      expression in vivo. Here, we show that Tax is expressed in a minor fraction of
      leukemic cells at any given time, and importantly, its expression spontaneously
      switches between on and off states. Live cell imaging revealed that the average
      duration of one episode of Tax expression is ~19 hours. Knockdown of Tax rapidly
      induced apoptosis in most cells, indicating that Tax is critical for maintaining
      the population, even if its short-term expression is limited to a small
      subpopulation. Single-cell analysis and computational simulation suggest that
      transient Tax expression triggers antiapoptotic machinery, and this effect
      continues even after Tax expression is diminished; this activation of the
      antiapoptotic machinery is the critical event for maintaining the population. In
      addition, Tax is induced by various cytotoxic stresses and also promotes HTLV-1
      replication. Thus, it seems that Tax protects infected cells from apoptosis and
      increases the chance of viral transmission at a critical moment. Keeping the
      expression of Tax minimal but inducible on demand is, therefore, a fundamental
      strategy of HTLV-1 to promote persistent infection and leukemogenesis.

PMID- 29358407
TI  - Motile cilia of human airway epithelia contain hedgehog signaling components that
      mediate noncanonical hedgehog signaling.
AB  - Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in
      the thin layer of liquid covering the airway surface. Although previous studies
      showed that vertebrate HH signaling requires primary cilia, as airway epithelia
      mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus,
      whether airway epithelia have apical receptors for SHH has remained unknown. We
      discovered that motile cilia on airway epithelial cells have HH signaling
      proteins, including patched and smoothened. These cilia also have proteins
      affecting cAMP-dependent signaling, including Galphai and adenylyl cyclase 5/6.
      Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat
      frequency and pH in airway surface liquid. These results suggest that apical SHH
      may mediate noncanonical HH signaling through motile cilia to dampen respiratory
      defenses at the contact point between the environment and the lung, perhaps
      counterbalancing processes that stimulate airway defenses.

PMID- 29358410
TI  - Transit-time and age distributions for nonlinear time-dependent compartmental
      systems.
AB  - Many processes in nature are modeled using compartmental systems
      (reservoir/pool/box systems). Usually, they are expressed as a set of first-order
      differential equations describing the transfer of matter across a network of
      compartments. The concepts of age of matter in compartments and the time required
      for particles to transit the system are important diagnostics of these models
      with applications to a wide range of scientific questions. Until now, explicit
      formulas for transit-time and age distributions of nonlinear time-dependent
      compartmental systems were not available. We compute densities for these types of
      systems under the assumption of well-mixed compartments. Assuming that a solution
      of the nonlinear system is available at least numerically, we show how to
      construct a linear time-dependent system with the same solution trajectory. We
      demonstrate how to exploit this solution to compute transit-time and age
      distributions in dependence on given start values and initial age distributions.
      Furthermore, we derive equations for the time evolution of quantiles and moments
      of the age distributions. Our results generalize available density formulas for
      the linear time-independent case and mean-age formulas for the linear time
      dependent case. As an example, we apply our formulas to a nonlinear and a linear
      version of a simple global carbon cycle model driven by a time-dependent input
      signal which represents fossil fuel additions. We derive time-dependent age
      distributions for all compartments and calculate the time it takes to remove
      fossil carbon in a business-as-usual scenario.

PMID- 29358411
TI  - Dendritic Cells on the Way to Glory.

PMID- 29358409
TI  - Structure and function of the archaeal response regulator CheY.
AB  - Motility is a central feature of many microorganisms and provides an efficient
      strategy to respond to environmental changes. Bacteria and archaea have developed
      fundamentally different rotary motors enabling their motility, termed flagellum
      and archaellum, respectively. Bacterial motility along chemical gradients, called
      chemotaxis, critically relies on the response regulator CheY, which, when
      phosphorylated, inverses the rotational direction of the flagellum via a switch
      complex at the base of the motor. The structural difference between archaellum
      and flagellum and the presence of functional CheY in archaea raises the question
      of how the CheY protein changed to allow communication with the archaeal motility
      machinery. Here we show that archaeal CheY shares the overall structure and
      mechanism of magnesium-dependent phosphorylation with its bacterial counterpart.
      However, bacterial and archaeal CheY differ in the electrostatic potential of the
      helix alpha4. The helix alpha4 is important in bacteria for interaction with the
      flagellar switch complex, a structure that is absent in archaea. We demonstrated
      that phosphorylation-dependent activation, and conserved residues in the archaeal
      CheY helix alpha4, are important for interaction with the archaeal-specific
      adaptor protein CheF. This forms a bridge between the chemotaxis system and the
      archaeal motility machinery. Conclusively, archaeal CheY proteins conserved the
      central mechanistic features between bacteria and archaea, but differ in the
      helix alpha4 to allow binding to an archaellum-specific interaction partner.

PMID- 29358412
TI  - Pillars Article: Efficient presentation of soluble antigen by cultured human
      dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor
      plus interleukin 4 and downregulated by tumor necrosis factor alpha. J. Exp. Med.
      1994. 179:1109-1118.

PMID- 29358414
TI  - Quality of family relationships and outcomes of dementia: a systematic review.
AB  - OBJECTIVES: To evaluate the association between the quality of relationship
      between a person with dementia and their family carer and outcomes for the person
      with dementia. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Cohort studies of
      people with clinically diagnosed dementia and their main carers. Exposures of
      interest were any elements of relationship quality, for example, attachment
      style, expressed emotion and coping style. Our primary outcome was
      institutionalisation, and secondary outcomes were hospitalisation, death, quality
      of life and behavioural and psychiatric symptoms of dementia ('challenging
      behaviour'). DATA SOURCES: MEDLINE, Embase, Web of Science, PsycInfo, the
      Cochrane Library and Opengrey were searched from inception to May 2017. STUDY
      APPRAISAL AND SYNTHESIS METHODS: The Newcastle-Ottawa Scale was used to assess
      risk of bias. A narrative synthesis of results was performed due to differences
      between studies. RESULTS: Twenty studies were included. None of the studies
      controlled for all prespecified confounding factors (age, gender, socioeconomic
      status and severity of dementia). Reporting of results was inadequate with many
      studies simply reporting whether associations were 'statistically significant'
      without providing effect size estimates or CIs. There was a suggestion of an
      association between relationship factors and global challenging behaviour. All
      studies evaluating global challenging behaviour provided statistical evidence of
      an association (most P values below 0.02). There was no consistent evidence for
      an association for any other outcome assessed. CONCLUSIONS: There is currently no
      strong or consistent evidence on the effects of relationship factors on
      institutionalisation, hospitalisation, death or quality of life for people with
      dementia. There was a suggestion of an association between relationship factors
      and challenging behaviour, although the evidence for this was weak. To improve
      our ability to support those with dementia and their families, further robust
      studies are needed. PROSPERO REGISTRATION NUMBER: CRD42015020518.

PMID- 29358415
TI  - Identifying patients at risk of inhospital death or hospice transfer for early
      goals of care discussions in a US referral center: the HELPS model derived from
      retrospective data.
AB  - OBJECTIVE: Create a score to identify patients at risk of death or hospice
      placement who may benefit from goals of care discussion earlier in the
      hospitalisation. DESIGN: Retrospective cohort study to develop a risk index using
      multivariable logistic regression. SETTING: Two tertiary care hospitals in
      Southeastern Minnesota. PARTICIPANTS: 92 879 adult general care admissions (50%
      male, average age 60 years). PRIMARY AND SECONDARY OUTCOME MEASURES: Our outcome
      measure was an aggregate of inhospital death or discharge to hospice. Predictor
      variables for the model encompassed comorbidities, nutrition status, functional
      status, demographics, fall risk, mental status, Charlson Comorbidity Index and
      acuity of illness on admission. Resuscitation status, race, geographic area of
      residence and marital status were added as covariates to account for confounding.
      RESULTS: Inhospital mortality and discharge to hospice were rare, with incidences
      of 1.2% and 0.8%, respectively. The Hospital End-of-Life Prognostic Score (HELPS)
      demonstrated good discrimination (C-statistic=0.866 in derivation set and 0.834
      in validation set). The patients with the highest 5% of scores had an 8% risk of
      the outcome measure, relative risk 12.9 (10.9-15.4) when compared to the bottom
      95%. CONCLUSIONS: HELPS is able to identify patients with a high risk of
      inhospital death or need for hospice at discharge. These patients may benefit
      from early goals of care discussions.

PMID- 29358413
TI  - The Hypoxia-Adenosine Link during Intestinal Inflammation.
AB  - Intestinal inflammation is a key element in inflammatory bowel disease and is
      related to a combination of factors, including genetics, mucosal barrier
      dysfunction, bacteria translocation, deleterious host-microbe interactions, and
      dysregulated immune responses. Over the past decade, it has been appreciated that
      these inflammatory lesions are associated with profound tissue hypoxia.
      Interestingly, an endogenous adaptive response under the control of hypoxia
      signaling is enhancement in adenosine signaling, which impacts these different
      endpoints, including promoting barrier function and encouraging anti-inflammatory
      activity. In this review, we discuss the hypoxia-adenosine link in inflammatory
      bowel disease, intestinal ischemia/reperfusion injury, and colon cancer. In
      addition, we provide a summary of clinical implications of hypoxia and adenosine
      signaling in intestinal inflammation and disease.

PMID- 29358416
TI  - Retrospective analysis assessing the spatial and temporal distribution of
      paediatric acute respiratory tract infections in Ho Chi Minh City, Vietnam.
AB  - BACKGROUND: Acute respiratory tract infections (ARIs) are the leading cause of
      morbidity and mortality in young children in low/middle-income countries. Using
      routine hospital data, we aimed to examine the spatial distribution, temporal
      trends and climatic risk factors of paediatric ARIs in Vietnam. METHODS: Data
      from hospitalised paediatric (<16 years) patients with ARIs residing in Ho Chi
      Minh City (HCMC) between 2005 and 2010 were retrieved from the two main
      Children's Hospitals and the Hospital for Tropical Diseases in HCMC. Spatial
      mapping and time series analysis were performed after disaggregating data into
      upper respiratory tract infections (URIs) and lower respiratory tract infections
      (LRIs). RESULTS: Over the study period, there were 155 999 paediatric patients
      admitted with ARIs (33% of all hospital admissions). There were 68 120 URIs (14%)
      and 87 879 LRIs (19%). The most common diagnoses were acute pharyngitis (28% of
      all ARI), pneumonia (21%), bronchitis (18%) and bronchiolitis (16%). A
      significant increasing trend over time was found for both URIs (mean weekly
      incidence per 1000 population, I=3.12), incidence rate ratio for 1-week increase
      in time (RR 1.0, 95% CI 1.02 to 1.17) for URI and (I=4.02, RR 1.08 (95% CI 1.006
      to 1.16)) for LRI. The weekly URI incidence peaked in May-June and was
      significantly associated with lags in weekly URI incidence and the average
      humidity, rainfall and water level. The weekly LRI incidence exhibited
      significant seasonality (P<0.0001), with an annual peak in September-October and
      was significantly associated with lags in weekly LRI incidence and lags in weekly
      average temperature, rainfall and water level. CONCLUSIONS: ARIs are a leading
      cause of childhood hospitalisation in HCMC, Vietnam. The incidence of ARIs was
      higher in the wet season and in specific HCMC districts. These results may guide
      health authorities in where and when to effectively allocate resources for the
      prevention and control of ARIs.

PMID- 29358418
TI  - Smartphone Smoking Cessation Application (SSC App) trial: a multicountry double
      blind automated randomised controlled trial of a smoking cessation decision-aid
      'app'.
AB  - OBJECTIVE: To assess the efficacy of an interactive smoking cessation decision
      aid application (pp) compared with a smoking cessation static information app on
      continuous abstinence. DESIGN: Automated double-blind randomised controlled trial
      with 6 months follow-up (2014-2015). SETTING: Smartphone-based. PARTICIPANTS: 684
      participants (daily smokers of cigarettes, 18 years old or over) recruited
      passively from app stores in the USA, Australia, UK and Singapore, and randomised
      to one of two sub-apps. INTERVENTIONS: Behavioural, decision-aid, smartphone
      application. MAIN OUTCOMES: Continuous abstinence at 10 days, 1 month, 3 months
      and 6 months. RESULTS: Smokers who received the decision-aid app were more likely
      to be continuously abstinent at 1 month compared with the information-only app
      (28.5% vs 16.9%; relative risk (RR) 1.68; 95% CI 1.25 to 2.28). The effect was
      sustained at 3 months (23.8% vs 10.2%; RR 2.08; 95% CI 1.38 to 3.18) and 6 months
      (10.2% vs 4.8%; RR 2.02; 95% CI 1.08 to 3.81). Participants receiving the
      decision-aid app were also more likely to have made an informed choice (31.9% vs
      19.6%) and have lower decisional conflict (19.5% vs 3.9%). CONCLUSION: A
      smartphone decision-aid app with support features significantly increased smoking
      cessation and informed choice. With an increasing number of smokers attempting to
      quit, unassisted evidence-based decision-aid apps can provide an effective and
      user-friendly option to many who are making quit decisions without healthcare
      professionals. TRIAL REGISTRATION NUMBER: ACTRN12613000833763.

PMID- 29358417
TI  - Economic impact of medication non-adherence by disease groups: a systematic
      review.
AB  - OBJECTIVE: To determine the economic impact of medication non-adherence across
      multiple disease groups. DESIGN: Systematic review. EVIDENCE REVIEW: A
      comprehensive literature search was conducted in PubMed and Scopus in September
      2017. Studies quantifying the cost of medication non-adherence in relation to
      economic impact were included. Relevant information was extracted and quality
      assessed using the Drummond checklist. RESULTS: Seventy-nine individual studies
      assessing the cost of medication non-adherence across 14 disease groups were
      included. Wide-scoping cost variations were reported, with lower levels of
      adherence generally associated with higher total costs. The annual adjusted
      disease-specific economic cost of non-adherence per person ranged from $949 to
      $44 190 (in 2015 US$). Costs attributed to 'all causes' non-adherence ranged from
      $5271 to $52 341. Medication possession ratio was the metric most used to
      calculate patient adherence, with varying cut-off points defining non-adherence.
      The main indicators used to measure the cost of non-adherence were total cost or
      total healthcare cost (83% of studies), pharmacy costs (70%), inpatient costs
      (46%), outpatient costs (50%), emergency department visit costs (27%), medical
      costs (29%) and hospitalisation costs (18%). Drummond quality assessment yielded
      10 studies of high quality with all studies performing partial economic
      evaluations to varying extents. CONCLUSION: Medication non-adherence places a
      significant cost burden on healthcare systems. Current research assessing the
      economic impact of medication non-adherence is limited and of varying quality,
      failing to provide adaptable data to influence health policy. The correlation
      between increased non-adherence and higher disease prevalence should be used to
      inform policymakers to help circumvent avoidable costs to the healthcare system.
      Differences in methods make the comparison among studies challenging and an
      accurate estimation of true magnitude of the cost impossible. Standardisation of
      the metric measures used to estimate medication non-adherence and development of
      a streamlined approach to quantify costs is required. PROSPERO REGISTRATION
      NUMBER: CRD42015027338.

PMID- 29358419
TI  - Disparities in spread and control of influenza in slums of Delhi: findings from
      an agent-based modelling study.
AB  - OBJECTIVES: This research studies the role of slums in the spread and control of
      infectious diseases in the National Capital Territory of India, Delhi, using
      detailed social contact networks of its residents. METHODS: We use an agent-based
      model to study the spread of influenza in Delhi through person-to-person contact.
      Two different networks are used: one in which slum and non-slum regions are
      treated the same, and the other in which 298 slum zones are identified. In the
      second network, slum-specific demographics and activities are assigned to the
      individuals whose homes reside inside these zones. The main effects of
      integrating slums are that the network has more home-related contacts due to
      larger family sizes and more outside contacts due to more daily activities
      outside home. Various vaccination and social distancing interventions are applied
      to control the spread of influenza. RESULTS: Simulation-based results show that
      when slum attributes are ignored, the effectiveness of vaccination can be
      overestimated by 30%-55%, in terms of reducing the peak number of infections and
      the size of the epidemic, and in delaying the time to peak infection. The slum
      population sustains greater infection rates under all intervention scenarios in
      the network that treats slums differently. Vaccination strategy performs better
      than social distancing strategies in slums. CONCLUSIONS: Unique characteristics
      of slums play a significant role in the spread of infectious diseases. Modelling
      slums and estimating their impact on epidemics will help policy makers and
      regulators more accurately prioritise allocation of scarce medical resources and
      implement public health policies.

PMID- 29358420
TI  - Comparative efficacy and acceptability of antiepileptic drugs for classical
      trigeminal neuralgia: a Bayesian network meta-analysis protocol.
AB  - INTRODUCTION: Trigeminal neuralgia (TN) affects 4 to 28.9/100 000 people
      worldwide, and antiepileptic drugs such as carbamazepine and oxcarbazepine are
      the firstline treatment options. However, the efficacy and safety of other
      antiepileptic drugs remain unclear due to insufficient direct comparisons.
      OBJECTIVE: To compare the efficacy and acceptability of all currently available
      antiepileptic agents for the treatment of patients with classical TN. METHODS: We
      will search the PubMed, EMBASE, Cochrane Library and Web of Science databases for
      unpublished or undergoing research listed in registry platforms. We will include
      all randomised controlled trials comparing two different antiepileptic drugs or
      one antiepileptic drug with placebo in patients with classical TN. The primary
      outcomes will be the proportion of responders and the number of subjects who
      dropout during the treatment. The secondary outcomes will include the two primary
      outcomes but in the follow-up period, changes in the self-reporting assessment
      scale for neuralgia and quality of life assessment. In terms of network meta
      analysis, we will fit our model to a Bayesian framework using the JAGS and
      pcnetmeta packages of the R project. ETHICS AND DISSEMINATION: This protocol will
      not disseminate any private patient data. The results of this review will be
      disseminated through peer reviewed publication. PROSPERO REGISTRATION NUMBER:
      CRD42016048640.

PMID- 29358422
TI  - 'I did try and point out about his dignity': a qualitative narrative study of
      patients and carers' experiences and expectations of junior doctors.
AB  - OBJECTIVES: For many years, the voice of patients has been understood as a
      critical element for the improvement of care quality in healthcare settings. How
      well medical graduates are prepared for clinical practice is an important
      question, but one that has rarely been considered from patient and public
      perspectives. We aimed to fill this gap by exploring patients and carers'
      experiences and expectations of junior doctors. DESIGN: This comprises part of a
      wider study on UK medical graduates' preparedness for practice. A qualitative
      narrative methodology was used, comprising four individual and six group
      interviews. PARTICIPANTS: 25 patients and carers from three UK countries.
      ANALYSIS: Data were transcribed, anonymised and analysed using framework
      analysis. MAIN RESULTS: We identified three themes pertinent to answering our
      research question: (1) sources of knowledge (sources of information contributing
      to patients and carers' perceptions of junior doctors' impacting on
      expectations); (2) desires for student/trainee learning (experiences and
      expectations of medical training); and (3) future doctors (experiences and
      expectations of junior doctors). We also highlight metaphorical talk and humour,
      where relevant, in the quotes presented to give deeper insights into
      participants' perspectives of the issues. Participants focused on personal and
      interpersonal aspects of being a doctor, such as respect and communication. There
      was a strong assertion that medical graduates needed to gain direct experience
      with a diverse range of patients to encourage individualised care. Participants
      narrated their experiences of having symptoms ignored and attributed to an
      existing diagnosis ('diagnostic overshadowing') and problems relating to
      confidentiality. CONCLUSIONS: Our findings support the view that patients and
      carers have clear expectations about junior doctors, and that patient views are
      important for preparing junior doctors for practice. There is a necessity for
      greater dialogue between patients, doctors and educators to clarify expectations
      and confidentiality issues around patient care.

PMID- 29358421
TI  - Evaluating dengue burden in Africa in passive fever surveillance and
      seroprevalence studies: protocol of field studies of the Dengue Vaccine
      Initiative.
AB  - INTRODUCTION: Dengue is an important and well-documented public health problem in
      the Asia-Pacific and Latin American regions. However, in Africa, information on
      disease burden is limited to case reports and reports of sporadic outbreaks, thus
      hindering the implementation of public health actions for disease control. To
      gather evidence on the undocumented burden of dengue in Africa, epidemiological
      studies with standardised methods were launched in three locations in Africa.
      METHODS AND ANALYSIS: In 2014-2017, the Dengue Vaccine Initiative initiated field
      studies at three sites in Ouagadougou, Burkina Faso; Lambarene, Gabon and
      Mombasa, Kenya to obtain comparable incidence data on dengue and assess its
      burden through standardised hospital-based surveillance and community-based
      serological methods. Multidisciplinary measurements of the burden of dengue were
      obtained through field studies that included passive facility-based fever
      surveillance, cost-of-illness surveys, serological surveys and healthcare
      utilisation surveys. All three sites conducted case detection using standardised
      procedures with uniform laboratory assays to diagnose dengue. Healthcare
      utilisation surveys were conducted to adjust population denominators in incidence
      calculations for differing healthcare seeking patterns. The fever surveillance
      data will allow calculation of age-specific incidence rates and comparison of
      symptomatic presentation between patients with dengue and non-dengue using
      multivariable logistic regression. Serological surveys assessed changes in immune
      status of cohorts of approximately 3000 randomly selected residents at each site
      at 6-month intervals. The age-stratified serosurvey data will allow calculation
      of seroprevalence and force of infection of dengue. Cost-of-illness evaluations
      were conducted among patients with acute dengue by Rapid Diagnostic Test. ETHICS
      AND DISSEMINATION: By standardising methods to evaluate dengue burden across
      several sites in Africa, these studies will generate evidence for dengue burden
      in Africa and data will be disseminated as publication in peer-review journals in
      2018.

PMID- 29358423
TI  - Cost-effectiveness of an internet-based perioperative care programme to enhance
      postoperative recovery in gynaecological patients: economic evaluation alongside
      a stepped-wedge cluster-randomised trial.
AB  - OBJECTIVES: To evaluate the cost-effectiveness and cost-utility of an internet
      based perioperative care programme compared with usual care for gynaecological
      patients. DESIGN: Economic evaluation from a societal perspective alongside a
      stepped-wedge cluster-randomised controlled trial with 12 months of follow-up.
      SETTING: Secondary care, nine hospitals in the Netherlands, 2011-2014.
      PARTICIPANTS: 433 employed women aged 18-65 years scheduled for a hysterectomy
      and/or laparoscopic adnexal surgery. INTERVENTION: The intervention comprised an
      internet-based care programme aimed at improving convalescence and preventing
      delayed return to work (RTW) following gynaecological surgery and was
      sequentially rolled out. Depending on the implementation phase of their hospital,
      patients were allocated to usual care (n=206) or to the intervention (n=227).
      MAIN OUTCOME MEASURES: The primary outcome was duration until full sustainable
      RTW. Secondary outcomes were quality-adjusted life years (QALYs), health-related
      quality of life and recovery. RESULTS: At 12 months, there were no statistically
      significant differences in total societal costs (?-647; 95% CI ?-2116 to ?753)
      and duration until RTW (-4.1; 95% CI -10.8 to 2.6) between groups. The
      incremental cost-effectiveness ratio (ICER) for RTW was 56; each day earlier RTW
      in the intervention group was associated with cost savings of ?56 compared with
      usual care. The probability of the intervention being cost-effective was 0.79 at
      a willingness-to-pay (WTP) of ?0 per day earlier RTW, which increased to 0.97 at
      a WTP of ?76 per day earlier RTW. The difference in QALYs gained over 12 months
      between the groups was clinically irrelevant resulting in a low probability of
      cost-effectiveness for QALYs. CONCLUSIONS: Considering that on average the costs
      of a day of sickness absence are ?230, the care programme is considered cost
      effective in comparison with usual care for duration until sustainable RTW after
      gynaecological surgery for benign disease. Future research should indicate
      whether widespread implementation of this care programme has the potential to
      reduce societal costs associated with gynaecological surgery. TRIAL REGISTRATION
      NUMBER: NTR2933; Results.

PMID- 29358424
TI  - Study protocol for One Health data collections, analyses and intervention of the
      Sino-Swedish integrated multisectoral partnership for antibiotic resistance
      containment (IMPACT).
AB  - INTRODUCTION: To effectively minimise the emergence and dissemination of
      antibiotic resistant bacteria, a holistic One Health approach is called for. The
      Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance
      Containment is a cross-sectoral and integrated project on antibiotic resistance,
      conducted in Shandong Province in China. This paper outlines the overall study
      protocol for the project. To our knowledge, this is the first research programme
      aiming to take a true holistic approach across multiple sectors simultaneously in
      China, and the first to incorporate both antibiotic use and infection prevention
      and control in addition to antibiotic resistance patterns. The project aims to
      address gaps in current knowledge and seeks to improve the situation through a
      system-wide intervention. By using a One Health approach we can address important
      research questions that individual discipline investigations are unable to. The
      results obtained should thus more closely reflect the world in which human
      health, animal health and the environment are inextricably and intimately
      interlinked. METHODS AND ANALYSIS: Both quantitative and qualitative studies are
      included for households from 12 villages, their surrounding environment and a
      tertiary care hospital in a nearby town. The studies include analyses of
      antibiotic consumption for humans and pigs; qualitative and quantitative data on
      perceptions, knowledge and attitudes; faecal carriage of extended spectrum beta
      lactamase and carbapenemase-producing Enterobacteriaceae from pigs and humans,
      and occurrence in household drinking water, surface water, waste water and
      clinical bacterial isolates from the hospital. Carriage of methicillin-resistant
      Staphylococcus aureus in humans, household pigs and clinical bacterial isolates
      is also investigated. Furthermore, potential inter-relationships between these
      sources are analysed. A multifaceted One Health intervention is designed and
      implemented in 6 of the 12 villages. Repeated and continuous data collections
      take place over 2 years, where the repeated data collection is performed after 1
      year of intervention. Comparisons are made between intervention and control
      villages, before and after the intervention. ETHICS: Ethics approval was obtained
      from the first Affiliated Hospital, College of Medicine, Zhejiang University,
      China, reference number 2015#185 and 2015#283.

PMID- 29358425
TI  - Qualitative findings on building a partnered approach to implementation of a
      group-based diabetes intervention in VA primary care.
AB  - OBJECTIVE: Conduct a formative evaluation to inform the implementation of
      'Empowering Patients in Chronic Care' (EPIC), an evidence-based interdisciplinary
      group medical appointment intervention to improve collaborative goal-setting in
      patients with treated but uncontrolled diabetes. DESIGN: The formative evaluation
      involved qualitative, in-depth interviews with clinicians, structured according
      to the Promoting Action on Research in Health Services framework. Interviews
      elicited (1) participants' knowledge regarding interdisciplinary group self
      management and goal-setting programmes and how well clinicians embrace these
      interventions (evidence), (2) physical and social climate at each target facility
      and how the intervention can best be embedded into routine primary care (context)
      and (3) site-specific needs to be addressed by our implementation team and
      clinicians' preparedness and intentions to participate in the intervention
      (facilitation). SETTING: Clinicians were part of a primary care setting at one of
      five participating medical facilities within one Veterans Health Administration
      Veterans Affairs regional network. PARTICIPANTS: We interviewed a snowball sample
      of 35 interdisciplinary clinicians engaged in diabetes management, practising
      leadership and administrators at target sites. RESULTS: Most participants had
      previous experience with diabetes group self-management programmes and viewed
      group appointments as an effective approach to enhancing care. Discussions about
      existing group appointments provided a context for evaluating potential barriers
      and facilitators to implementing EPIC into target sites. Interviews revealed
      clinicians' expectations about the roles they would play in the intervention,
      their assessments of the roles and strategies to facilitate their performance in
      those roles. CONCLUSIONS: Successful implementation of evidence-based practices
      into routine care requires a partnered approach with engaged local staff. The
      intervention should address local goals and research objectives to encourage
      bidirectional engagement. Robust partnerships are nurtured further by sustained,
      open communication and must consider the context, target population and local
      experience to address barriers and facilitators to implementation.

PMID- 29358426
TI  - Small cortical grey matter lesions show no persistent infarction in transient
      ischaemic attack? A prospective cohort study.
AB  - OBJECTIVES: To find determining factors for persistent infarction signs in
      patients with transient ischaemic attack (TIA), herein initial diffusion lesion
      size, visibility on apparent diffusion coefficient (ADC) or fluid-attenuated
      inversion recovery (FLAIR) and location. DESIGN: Prospective cohort study of
      patients with clinical TIA receiving 3T-MRI within 72 hours of symptom onset and
      at 8-week follow-up. SETTING: Clinical workflow in a single tertiary stroke
      centre between February 2012 and June 2014. PARTICIPANTS: 199 candidate patients
      were recruited, 64 patients were excluded due to non-TIA discharge diagnosis or
      no 8-week MRI. 122 patients completed the study. PRIMARY OUTCOME MEASURES: The
      primary outcome was visible persistent infarction defined as 8-week FLAIR
      hyperintensity or atrophy corresponding to the initial diffusion-weighted imaging
      (DWI) lesion. RESULTS: 50 patients showed 84 initial DWI lesions. 29 (35%) DWI
      lesions did not result in infarction signs on 8-week FLAIR. 26 (90%, P<0.0001)
      reversing lesions were located in the cortical grey matter (cGM). cGM location
      (vs any other location) strongly predicted no 8-week infarction sign development
      (OR 0.02, 95% CI 0.001 to 0.17) or partial lesion area decrease (>30% of initial
      DWI-area, OR 14.10, 95% CI 3.61 to 54.72), adjusted for FLAIR-visibility, DWI
      area, ADC-confirmation and time to scan (TTS) from symptom onset to baseline MRI.
      Acute FLAIR-visibility was a strong associated factor for persistent infarction
      signs (OR 33.06, 95% CI 2.94 to 1432.34). For cGM lesions area size was sole
      associated factor for persistent infarction signs with a 0.31 cm2 (area under the
      curve (AUC), 0.97) threshold. In eight (16%) DWI-positive patients, all lesions
      reversed fully. CONCLUSIONS: 16% of DWI-positive patients and one-third of acute
      DWI lesions caused no persistent infarction signs, especially small cGM lesions
      were not followed by development of persistent infarction signs. Late MRI after
      TIA is likely to be less useful in the clinical setting, and it is dubious if the
      absence of old vascular lesions can be taken as evidence of no prior ischaemic
      attacks. TRIAL REGISTRATION NUMBER: NCT01531946; Results.

PMID- 29358427
TI  - The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of
      care for patients with non-specific symptoms of cancer.
AB  - INTRODUCTION: Cancer survival in England lags behind most European countries, due
      partly to lower rates of early stage diagnosis. We report the protocol for the
      evaluation of a multidisciplinary diagnostic centre-based pathway for the
      investigation of 'low-risk but not no-risk' cancer symptoms called the Suspected
      CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in
      Oxfordshire; one of a number of pathways implemented during the second wave of
      the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to
      improve England's cancer survival rates through establishing effective routes to
      early diagnosis. METHODS AND ANALYSIS: To evaluate SCAN, we are collating a
      prospective database of patients referred onto the pathway by their general
      practitioner (GP). Patients aged over 40 years, with non-specific symptoms such
      as weight loss or fatigue, who do not meet urgent cancer referral criteria or for
      whom symptom causation remains unclear after investigation via other existing
      pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory
      testing and clinic review within 2 weeks. We will follow all patients in the
      primary and secondary care record for at least 2 years. The data will be used to
      understand the diagnostic yield of the SCAN pathway in the short term (28 days)
      and the long term (2 years). Routinely collected primary and secondary care data
      from patients not referred to SCAN but with similar symptoms will also be used to
      evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN
      to assess cost-effectiveness. Acceptability will be evaluated using patient and
      GP surveys. ETHICS AND DISSEMINATION: The Oxford Joint Research Office Study
      Classification Group has judged this to be a service evaluation and so outside of
      research governance. The results of this project will be disseminated by peer
      reviewed publication and presentation at conferences.

PMID- 29358428
TI  - Time trends in peripheral artery disease incidence, prevalence and secondary
      preventive therapy: a cohort study in The Health Improvement Network in the UK.
AB  - OBJECTIVES: To assess time trends in symptomatic peripheral artery disease (PAD)
      incidence and prevalence, and secondary preventive therapy. DESIGN: Cohort study
      using The Health Improvement Network. SETTING: UK primary care. PARTICIPANTS:
      Individuals aged 50-89 years identified annually between 2000 and 2014.
      Participants with symptomatic PAD were identified using Read codes. OUTCOME
      MEASURES: Incidence and prevalence of symptomatic PAD from 2000 to 2014, overall
      and by sex and age. Proportion of patients prescribed secondary preventive
      therapy with acetylsalicylic acid (ASA), clopidogrel, an ACE inhibitor, an
      angiotensin receptor blocker (ARB) and/or a statin. RESULTS: The incidence of
      symptomatic PAD per 10 000 person-years decreased over time, from 38.6 (men:
      51.0; women: 28.7) in 2000 to 17.3 (men: 23.1; women: 12.4) in 2014. The
      prevalence of symptomatic PAD decreased from 3.4% (men: 4.5%; women: 2.5%) in
      2000 to 2.4% (men: 3.1%; women: 1.7%) in 2014. Incidence and prevalence decreases
      were observed in all age groups. The proportions of patients prescribed ASA
      monotherapy, clopidogrel monotherapy and dual antiplatelet therapy in the 2
      months after PAD diagnosis were 42.7%, 2.9% and 2.5%, respectively, during 2000
      2003, and 44.7%, 11.0% and 5.2%, respectively, during 2012-2014. For ACE
      inhibitor/ARB therapy and statins, proportions in the 2 months after diagnosis
      were 30.2% and 31.2%, respectively, during 2000-2003, and 45.1% and 65.9%,
      respectively, during 2012-2014. CONCLUSION: The incidence and prevalence of
      symptomatic PAD diagnosed in UK primary care are decreasing. A large proportion
      of the population with PAD in clinical practice does not receive guideline
      recommended secondary prevention therapy.

PMID- 29358429
TI  - The journey through care: study protocol for a longitudinal qualitative interview
      study to investigate the healthcare experiences and preferences of children and
      young people with life-limiting and life-threatening conditions and their
      families in the West Midlands, UK.
AB  - INTRODUCTION: The number of children and young people living with life-limiting
      and life-threatening conditions is rising. Providing high-quality, responsive
      healthcare for them and for their families presents a significant challenge.
      Their conditions are often complex and highly unpredictable. Palliative care is
      advocated for people with life-limiting and life-threatening conditions, but
      these services for children are highly variable in terms of availability and
      scope. Little is known about the lived experiences and preferences of children
      and their families in terms of the palliative care that they do, or do not,
      receive. This study aims to produce an in-depth insight into the experiences and
      preferences of such children and families in order to develop recommendations for
      the future provision of services. The study will be carried out in the West
      Midlands, UK. METHODS AND ANALYSIS: A qualitative study comprising longitudinal
      interviews over a 12-month period with children (aged 5-18 years) living with
      life-limiting or life-threatening conditions and their family members. Data
      analysis will start with thematic analysis, followed by narrative and cross-case
      analysis to examine changing experiences and preferences over time, at the family
      level and within the wider healthcare system. Patient and public involvement
      (PPI) has informed the design and conduct of the study. Findings will be used to
      develop recommendations for an integrated model of palliative care for children
      in partnership with the patient and public involvement (PPI) group. ETHICS AND
      DISSEMINATION: Ethical approval was granted in September 2016 by the National
      Health Service Health Research Authority (IRAS ID: 196816, REC reference:
      16/WM/0272). Findings will be of immediate relevance to healthcare providers,
      policy-makers, commissioners and voluntary sector organisations in the UK and
      internationally. Reports will be prepared for these audiences, as well as for
      children and their families, alongside academic outputs.

PMID- 29358430
TI  - A cross-sectional analysis of the relationship between diabetes and health access
      barriers in an urban First Nations population in Canada.
AB  - OBJECTIVE: This study explores the relationship between health access barriers
      and diabetes in an urban First Nations population in Canada. DESIGN: Data from a
      self-identified urban First Nations population were collected using respondent
      driven sampling (RDS). As no clear approach for regression modelling of RDS data
      is available, two logistic regression modelling approaches, including survey
      based logistic and generalised linear mixed models, were used to explore the
      relationship between diabetes and health barriers of interest, including access
      to healthcare, food, housing and socioeconomic factors. SETTING: Hamilton,
      Ontario, Canada. PARTICIPANTS: This cross-sectional study used data collected
      from the Our Health Counts study, in partnership with the De dwa da dehs nye>s
      Aboriginal Health Centre, which recruited 554 First Nations adults living in
      Hamilton using RDS. RESULTS: After adjusting for covariates, multivariable
      regression techniques showed a statistically significant relationship between a
      self-reported diagnosis of diabetes and a lack of culturally appropriate care
      among urban First Nations peoples (OR: 12.70, 95% CI 2.52 to 57.91). There was
      also a trend towards a relationship between diabetes and not having a doctor
      available in the area, feeling that healthcare provided was inadequate and a lack
      of available healthcare services in the area. CONCLUSIONS: Urban First Nations
      peoples who felt the health service they received was not culturally appropriate
      were more likely to have diabetes, compared with those who did not feel the
      service they received was culturally inappropriate. Establishing more healthcare
      services that integrate First Nations cultures and traditions could improve
      access to care and the course of treatment for urban First Nations peoples living
      with diabetes.

PMID- 29358431
TI  - Seremban Cohort Study (SECOST): a prospective study of determinants and pregnancy
      outcomes of maternal glycaemia in Malaysia.
AB  - INTRODUCTION: Both gestational diabetes mellitus (GDM) and hyperglycaemia less
      severe than GDM are associated with risk of adverse pregnancy outcomes. We
      describe the study design of a prospective cohort of pregnant women recruited in
      early pregnancy with follow-ups of mothers and infants up to 2 years after birth.
      The primary aim of the study was to identify the determinants and outcomes of
      maternal glycaemia. METHODS AND ANALYSIS: Seremban Cohort Study (SECOST) is an
      ongoing prospective cohort study in which eligible pregnant women in first
      trimester (<10 weeks of gestation) are recruited from Maternal and Child Health
      clinics in Seremban District, Negeri Sembilan with seven follow-ups during
      pregnancy through 2 years postnatally. Infants are followed up every 6 months
      after birth until 2 years old. A standard 75 g oral glucose tolerance test is
      performed between 24 and 32 of weeks of gestation and as close to 28 weeks of
      gestation. Pregnancy and birth information are obtained from medical records.
      Sociodemographic, anthropometric, biochemical, dietary, physical activity,
      smoking, depression, child feeding and other data of mothers and infants are
      obtained at follow-ups. ETHICS AND DISSEMINATION: This study is approved by the
      Medical Research Ethics Committee (MREC), Universiti Putra Malaysia (UPM/FPSK/100
      9/2-MJKEtika) and MREC, Ministry of Health Malaysia (KKM/NIHSEC/08/0804/P12-
      613). Permission to conduct this study is also obtained from the Head of Seremban
      District Health Office. All participants are required to provide written informed
      consent prior to data collection. The research findings will be disseminated at
      journals and conference presentations.

PMID- 29358432
TI  - Longitudinal impact of interprofessional education on attitudes, skills and
      career trajectories: a protocol for a quasi-experimental study in New Zealand.
AB  - INTRODUCTION: Interprofessional practice is recognised as an important element of
      safe and effective healthcare. However, few studies exist that evaluate how
      preregistration education contributes to interprofessional competencies, and how
      these competencies develop throughout the early years of a health professional's
      career. This quasiexperimental study will gather longitudinal data during
      students' last year of preregistration training and their first 3 years of
      professional practice to evaluate the ongoing development of interprofessional
      competencies and the influence that preregistration education including an
      explicit interprofessional education (IPE) programme may have on these. METHODS
      AND ANALYSIS: Participants are students and graduates from the disciplines of
      dentistry, dietetics, medicine, nursing, occupational therapy, oral health,
      pharmacy and physiotherapy recruited before their final year of study. A subset
      of these students attended a 5-week IPE immersion programme during their final
      year of training. All data will be collected via five written or electronic
      surveys completed at 12-month intervals. Each survey will contain the Attitudes
      Towards Health Care Teams Scale and the Team Skills Scale, as well as
      quantitative and free-text items to explore vocational satisfaction, career
      trajectories and influences on these. Students who attend the IPE programme will
      complete additional free-text items to explore the effects of this programme on
      their careers. Quantitative analysis will compare scores at each time point,
      adjusted for baseline scores, for graduates who did and did not participate in
      the IPE programme. Associations between satisfaction data and discipline,
      professional setting, location and IPE participation will also be examined.
      Template analysis will explore free-text themes related to influences on career
      choices including participation in preregistration IPE. ETHICS AND DISSEMINATION:
      This study has received approval from the University of Otago Ethics Committee
      (D13/019). Results will be disseminated through peer-reviewed publications,
      conferences and stakeholder reports. Findings will inform future IPE developments
      and health workforce planning.

PMID- 29358434
TI  - Incidence and mortality of fractures by frailty level over 80 years of age:
      cohort study using UK electronic health records.
AB  - OBJECTIVE: This study aimed to estimate the association of frailty with incidence
      and mortality of fractures at different sites in people aged over 80 years.
      DESIGN: Cohort study. SETTING: UK family practices from 2001 to 2014.
      PARTICIPANTS: 265 195 registered participants aged 80 years and older.
      MEASUREMENTS: Frailty status classified into 'fit', 'mild', 'moderate' and
      'severe' frailty. Fractures, classified into non-fragility and fragility,
      including fractures of femur, pelvis, shoulder and upper arm, and forearm/wrist.
      Incidence of fracture, and mortality within 90 days and 1 year, were estimated.
      RESULTS: There were 28 643 fractures including: non-fragility fractures, 9101;
      femur, 12 501; pelvis, 2172; shoulder and upper arm, 4965; and forearm/wrist,
      6315. The incidence of each fracture type was higher in women and increased with
      frailty category (femur, severe frailty compared with 'fit', incidence rate ratio
      (IRR) 2.4, 95% CI 2.3 to 2.6). Fractures of the femur (95-99 years compared with
      80-84 years, IRR 2.7, 95% CI 2.6 to 2.9) and pelvis (IRR 2.9, 95% CI 2.5 to 3.3)
      were strongly associated with age but non-fragility and forearm fractures were
      not. Mortality within 90 days was greatest for femur fracture (adjusted HR,
      compared with forearm fracture 4.3, 95% CI 3.7 to 5.1). Mortality was higher in
      men and increased with age (HR 5.3, 95% CI 4.3 to 6.5 in those over 100 years
      compared with 80-84 years) but was less strongly associated with frailty
      category. Similar associations with fractures were seen at 1-year mortality.
      CONCLUSIONS: The incidence of fractures at all sites was higher in women and
      strongly associated with advancing frailty status, while the risk of mortality
      after a fracture was greater in men and was associated with age rather than
      frailty category.

PMID- 29358433
TI  - Randomised controlled trial to determine the efficacy and safety of prescribed
      water intake to prevent kidney failure due to autosomal dominant polycystic
      kidney disease (PREVENT-ADPKD).
AB  - INTRODUCTION: Maintaining fluid intake sufficient to reduce arginine vasopressin
      (AVP) secretion has been hypothesised to slow kidney cyst growth in autosomal
      dominant polycystic kidney disease (ADPKD). However, evidence to support this as
      a clinical practice recommendation is of poor quality. The aim of the present
      study is to determine the long-term efficacy and safety of prescribed water
      intake to prevent the progression of height-adjusted total kidney volume (ht-TKV)
      in patients with chronic kidney disease (stages 1-3) due to ADPKD. METHODS AND
      ANALYSIS: A multicentre, prospective, parallel-group, open-label, randomised
      controlled trial will be conducted. Patients with ADPKD (n=180; age <=65 years,
      estimated glomerular filtration rate (eGFR) >=30 mL/min/1.73 m2) will be
      randomised (1:1) to either the control (standard treatment+usual fluid intake) or
      intervention (standard treatment+prescribed fluid intake) group. Participants in
      the intervention arm will be prescribed an individualised daily fluid intake to
      reduce urine osmolality to <=270 mOsmol/kg, and supported with structured clinic
      and telephonic dietetic review, self-monitoring of urine-specific gravity, short
      message service text reminders and internet-based tools. All participants will
      have 6-monthly follow-up visits, and ht-TKV will be measured by MRI at 0, 18 and
      36 months. The primary end point is the annual rate of change in ht-TKV as
      determined by serial renal MRI in control vs intervention groups, from baseline
      to 3 years. The secondary end points are differences between the two groups in
      systemic AVP activity, renal disease (eGFR, blood pressure, renal pain), patient
      adherence, acceptability and safety. ETHICS AND DISSEMINATION: The trial was
      approved by the Human Research Ethics Committee, Western Sydney Local Health
      District. The results will inform clinicians, patients and policy-makers
      regarding the long-term safety, efficacy and feasibility of prescribed fluid
      intake as an approach to reduce kidney cyst growth in patients with ADPKD. TRIAL
      REGISTRATION NUMBER: ANZCTR12614001216606.

PMID- 29358435
TI  - Impact of maternal common mental disorders on child educational outcomes at 7 and
      9 years: a population-based cohort study in Ethiopia.
AB  - OBJECTIVES: To examine the association between exposure to maternal common mental
      disorders (CMD) in preschool and early school age children and subsequent child
      educational outcomes. DESIGN: A population-based cohort study. SETTING: The study
      was undertaken in the Butajira health and demographic surveillance site (HDSS), a
      predominantly rural area of south central Ethiopia. PARTICIPANTS: Inclusion
      criteria are women aged between 15 and 49 years, able to speak Amharic, in the
      third trimester of pregnancy and resident of the HDSS. 1065 women were recruited
      between July 2005 and February 2006 and followed up. When the average age of
      children was 6.5 years old, the cohort was expanded to include an additional 1345
      mothers and children who had been born in the 12 months preceding and following
      the recruitment of the original cohort, identified from the HDSS records. Data
      from a total of 2090 mother-child dyads were included in the current analysis.
      MEASURES: Maternal CMD was measured when the children were 6-7 (6/7) and 7-8
      (7/8) years old using the Self-reporting Questionnaire, validated for the
      setting. Educational outcomes (dropout) of the children at aged 7/8 years (end of
      2013/2014 academic year) were obtained from maternal report. At age 8/9 years
      (end of 2014/2015 academic year), educational outcomes (academic achievement,
      absenteeism and dropout) of the children were obtained from school records.
      RESULTS: After adjusting for potential confounders, exposure to maternal CMD at
      7/8 years was associated significantly with school dropout (OR 1.07; 95% CI 1.00
      to 1.13, P=0.043) and absenteeism (incidence rate ratio 1.01; 95% CI 1.00 to 1.02
      P=0.026) at the end of 2014/2015 academic year. There was no association between
      maternal CMD and child academic achievement. CONCLUSION: Future studies are
      needed to evaluate whether interventions to improve maternal mental health can
      reduce child school absenteeism and dropout.

PMID- 29358436
TI  - Associations between physical behaviour patterns and levels of depressive
      symptoms, anxiety and well-being in middle-aged adults: a cross-sectional study
      using isotemporal substitution models.
AB  - OBJECTIVE: To examine the compositional effects of physical behaviour on mental
      health. DESIGN: Cross-sectional study. SETTING: A population-representative
      random sample (Mitchelstown cohort) was recruited from a large primary care
      centre in Mitchelstown, County Cork, Ireland. PARTICIPANTS: In total 3807
      potential participants were selected from the practice list. Following exclusion
      of duplicates, deaths and ineligibles, 3043 were invited to participate and of
      these, 2047 (49.2% men) completed the questionnaire and physical examination
      components of the baseline assessment during the study period (April 2010 and May
      2011). Accelerometers were introduced into the study in January 2011. Of the 745
      participants seen between January and May of 2011, 475 (44.6% men) subjects
      (response rate 64%) agreed to participate and of these 397 (46.1% men) had valid
      accelerometer data. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants wore the
      wrist GENEActiv accelerometer for 7 consecutive days. Data were summarised into
      60 s epochs and activity categorised as sedentary behaviour, light or moderate-to
      vigorous physical activity (MVPA). Levels of depressive and anxiety symptoms were
      assessed using the Centre for Epidemiologic Studies Depression scale and the
      Hospital Anxiety and Depression Scale. Well-being was assessed using the WHO-5
      well-being scale. RESULTS: In adjusted isotemporal models, a 30 min increase in
      light activity per day was associated with a significant decrease in levels of
      anxiety symptoms (B=-0.34; 95% CI -0.64 to -0.04) and a significant increase in
      levels of well-being (B=0.58; 95% CI 0.05 to 1.11). No statistically significant
      associations were observed between any physical behaviour and depressive symptoms
      or when sedentary behaviour was substituted with MVPA (P>0.05). CONCLUSION:
      Although based on a cross-sectional study, the findings suggest that substituting
      light activity for sedentary behaviour may have positive associations with
      symptoms of anxiety and reported well-being among middle-aged adults.

PMID- 29358437
TI  - Developing a dementia-specific preference--based quality of life measure (AD-5D)
      in Australia: a valuation study protocol.
AB  - INTRODUCTION: Generic instruments for assessing health-related quality of life
      may lack the sensitivity to detect changes in health specific to certain
      conditions, such as dementia. The Quality of Life in Alzheimer's Disease (QOL-AD)
      is a widely used and well-validated condition-specific instrument for assessing
      health-related quality of life for people living with dementia, but it does not
      enable the calculation of quality-adjusted life years, the basis of cost utility
      analysis. This study will generate a preference-based scoring algorithm for a
      health state classification system -the Alzheimer's Disease Five Dimensions (AD
      5D) derived from the QOL-AD. METHODS AND ANALYSIS: Discrete choice experiments
      with duration (DCETTO) and best-worst scaling health state valuation tasks will
      be administered to a representative sample of 2000 members of the Australian
      general population via an online survey and to 250 dementia dyads (250 people
      with dementia and their carers) via face-to-face interview. A multinomial
      (conditional) logistic framework will be used to analyse responses and produce
      the utility algorithm for the AD-5D. ETHICS AND DISSEMINATION: The algorithms
      developed will enable prospective and retrospective economic evaluation of any
      treatment or intervention targeting people with dementia where the QOL-AD has
      been administered and will be available online. Results will be disseminated
      through journals that publish health economics articles and through professional
      conferences. This study has ethical approval.

PMID- 29358439
TI  - Inner-city green space and its association with body mass index and prevalent
      type 2 diabetes: a cross-sectional study in an urban German city.
AB  - OBJECTIVE: The accessibility of green space is an important aspect of the urban
      residential environment and has been found to be beneficial for health and well
      being. This study investigates the association between different indicators of
      green space and the outcomes body mass index (BMI) and prevalent type 2 diabetes
      in an urban population. DESIGN: Population-based cross-sectional study. SETTING:
      Dortmund, a city located in the industrial Ruhr area in Western Germany.
      PARTICIPANTS: 1312 participants aged 25-74 years from the Dortmund Health Study.
      METHODS: The participants' addresses were geocoded and shapefiles of statistical
      districts, road network and land use, as well as data on neighbourhood
      characteristics were obtained at baseline. Three indicators of green space were
      constructed using geographical information systems: proportion of green space,
      recreation location quotient (RLQ) weighted by population and distance to the
      next park or forest. Multilevel linear and logistic regression analyses on the
      association of green space with BMI and type 2 diabetes were performed, adjusted
      by individual-level characteristics and neighbourhood unemployment rate. RESULTS:
      The multilevel regression analyses showed no association between green space and
      BMI. In contrast, the three indicators of green space were significantly
      associated with type 2 diabetes. Residents of neighbourhoods with a low RLQ had a
      2.44 (95% CI 1.01 to 5.93) times higher odds to have type 2 diabetes compared
      with residents of high RLQ neighbourhoods. Likewise, residing more than 0.8 km
      away from the nearest park or forest increased the odds of type 2 diabetes (OR
      1.71, 95% CI 1.05 to 2.77). CONCLUSIONS: This study indicates that green space
      and its spatial accessibility might play a role in the development of type 2
      diabetes. Further research is needed to clarify this association.

PMID- 29358438
TI  - Study protocol for a prospective cohort study examining the predictive potential
      of dynamic symptom networks for the onset and progression of psychosis: the
      Mapping Individual Routes of Risk and Resilience (Mirorr) study.
AB  - INTRODUCTION: Our current ability to predict the course and outcome of early
      psychotic symptoms is limited, hampering timely treatment. To improve our
      understanding of the development of psychosis, a different approach to
      psychopathology may be productive. We propose to reconceptualise psychopathology
      from a network perspective, according to which symptoms act as a dynamic,
      interconnected system, impacting on each other over time and across diagnostic
      boundaries to form symptom networks. Adopting this network approach, the Mapping
      Individual Routes of Risk and Resilience study aims to determine whether
      characteristics of symptom networks can predict illness course and outcome of
      early psychotic symptoms. METHODS AND ANALYSIS: The sample consists of n=100
      participants aged 18-35 years, divided into four subgroups (n=4*25) with
      increasing levels of severity of psychopathology, representing successive stages
      of clinical progression. Individuals representing the initial stage have a
      relatively low expression of psychotic experiences (general population), whereas
      individuals representing the end stage are help seeking and display a
      psychometric expression of psychosis, putting them at ultra-high risk for
      transition to psychotic disorder. At baseline and 1-year follow-up, participants
      report their symptoms, affective states and experiences for three consecutive
      months in short, daily questionnaires on their smartphone, which will be used to
      map individual networks. Network parameters, including the strength and
      directionality of symptom connections and centrality indices, will be estimated
      and associated to individual differences in and within-individual progression
      through stages of clinical severity and functioning over the next 3 years. ETHICS
      AND DISSEMINATION: The study has been approved by the local medical ethical
      committee (ABR no. NL52974.042.15). The results of the study will be published in
      (inter)national peer-reviewed journals, presented at research, clinical and
      general public conferences. The results will assist in improving and fine-tuning
      dynamic models of psychopathology, stimulating both clinical and scientific
      progress. TRIAL REGISTRATION NUMBER: NTR6205 ; Pre-results.

PMID- 29358440
TI  - Impacts of Bicycle Infrastructure in Mid-Sized Cities (IBIMS): protocol for a
      natural experiment study in three Canadian cities.
AB  - INTRODUCTION: Bicycling is promoted as a transportation and population health
      strategy globally. Yet bicycling has low uptake in North America (1%-2% of trips)
      compared with European bicycling cities (15%-40% of trips) and shows marked sex
      and age trends. Safety concerns due to collisions with motor vehicles are primary
      barriers.To attract the broader population to bicycling, many cities are making
      investments in bicycle infrastructure. These interventions hold promise for
      improving population health given the potential for increased physical activity
      and improved safety, but such outcomes have been largely unstudied. In 2016, the
      City of Victoria, Canada, committed to build a connected network of
      infrastructure that separates bicycles from motor vehicles, designed to attract
      people of 'all ages and abilities' to bicycling.This natural experiment study
      examines the impacts of the City of Victoria's investment in a bicycle network on
      active travel and safety outcomes. The specific objectives are to (1) estimate
      changes in active travel, perceived safety and bicycle safety incidents; (2)
      analyse spatial inequities in access to bicycle infrastructure and safety
      incidents; and (3) assess health-related economic benefits. METHODS AND ANALYSIS:
      The study is in three Canadian cities (intervention: Victoria; comparison:
      Kelowna, Halifax). We will administer population-based surveys in 2016, 2018 and
      2021 (1000 people/city). The primary outcome is the proportion of people
      reporting bicycling. Secondary outcomes are perceived safety and bicycle safety
      incidents. Spatial analyses will compare the distribution of bicycle
      infrastructure and bicycle safety incidents across neighbourhoods and across
      time. We will also calculate the economic benefits of bicycling using WHO's
      Health Economic Assessment Tool. ETHICS AND DISSEMINATION: This study received
      approval from the Simon Fraser University Office of Research Ethics (study no.
      2016s0401). Findings will be disseminated via a website, presentations to
      stakeholders, at academic conferences and through peer-reviewed journal articles.

PMID- 29358442
TI  - Understanding the use of email consultation in primary care using a retrospective
      observational study with data of Dutch electronic health records.
AB  - OBJECTIVES: It is unclear why the use of email consultation is not more
      widespread in Dutch general practice, particularly because, since 2006, its costs
      can be reimbursed. To encourage further implementation, it is needed to
      understand the current use of email consultations. This study aims to understand
      the use of email consultation by different patient groups, compared with other
      general practice (GP) consultations. SETTING: For this retrospective
      observational study, we used Dutch routine electronic health record data obtained
      from NIVEL Primary Care Database for the years 2010 and 2014. PARTICIPANTS: 200
      general practices were included in 2010 (734 122 registered patients) and 434 in
      2014 (1 630 386 registered patients). PRIMARY OUTCOME MEASURES: The number and
      percentage of email consultations and patient characteristics (age, gender,
      neighbourhood socioeconomic status and diagnoses) of email consultation users
      were investigated and compared with those who had a telephone or face-to-face
      consultation. General practice characteristics were also taken into account.
      RESULTS: 32.0% of the Dutch general practices had at least one email consultation
      in 2010, rising to 52.8% in 2014. In 2014, only 0.7% of the GP consultations were
      by email (the others comprised home visits, telephone and face-to-face
      consultations). Its use highly varied among general practices. Most email
      consultations were done for psychological (14.7%); endocrine, metabolic and
      nutritional (10.9%); and circulatory (10.7%) problems. These diagnosis categories
      appeared less frequently in telephone and face-to-face consultations. Patients
      who had an email consultation were older than patients who had a telephone or
      face-to-face consultation. In contrast, patients with diabetes who had an email
      consultation were younger. CONCLUSION: Even though email consultation was done in
      half the general practices in the Netherlands in 2014, the actual use of it is
      extremely low. Patients who had an email consultation differ from those who had a
      telephone or face-to-face consultation. In addition, the use of email
      consultation by patients is dependent on its provision by GPs.

PMID- 29358443
TI  - Determinants of non-adherence to treatment for tuberculosis in high-income and
      middle-income settings: a systematic review protocol.
AB  - INTRODUCTION: Treatment for tuberculosis (TB) is highly effective if taken
      according to prescribed schedules. However, many people have difficulty adhering
      to treatment which can lead to poorer clinical outcomes, the development of drug
      resistance, increased duration of infectivity and consequent onward transmission
      of infection. A range of approaches are available to support adherence but in
      order to target these effectively a better understanding of the predictors of
      poor adherence is needed. This review aims to highlight the personal,
      sociocultural and structural factors that may lead to poor adherence in high
      income and middle-income settings. METHODS AND ANALYSIS: Seven electronic
      databases, Medline, EMBASE, CINAHL, PsycInfo, The Cochrane Library, Scopus and
      Web of Science, will be searched for relevant articles using a prespecified
      search strategy. Observational studies will be targeted to explore factors that
      influence adherence to treatment in individuals diagnosed with TB. Screening
      title and abstract followed by full-text screening and critical appraisal will be
      conducted by two researchers. Data will be extracted using the Population,
      Exposure, Comparator, Outcomes, Study characteristics framework. For cross-study
      assessment of strength of evidence for particular risk factors affecting
      adherence we will use the Grading of Recommendations, Assessment, Development and
      Evaluation tool modified for prognostic studies. A narrative synthesis of the
      studies will be compiled. A meta-analysis will be considered if there are
      sufficient numbers of studies that are homogenous in study design, population and
      outcomes. DISSEMINATION: A draft conceptual framework will be identified that (A)
      identifies key barriers to adherence at each contextual level (eg, personal,
      sociocultural, health systems) and (B) maps the relationships, pathways and
      mechanisms of effect between these factors and adherence outcomes for people with
      TB. The draft conceptual framework will guide targeting of adherence
      interventions and further research. PROSPERO REGISTRATION NUMBER: CRD42017061049.

PMID- 29358441
TI  - Monitoring intensive care unit performance-impact of a novel individualised
      performance scorecard in critical care medicine: a mixed-methods study protocol.
AB  - INTRODUCTION: Patients admitted to a critical care medicine (CCM) environment,
      including an intensive care unit (ICU), are susceptible to harm and significant
      resource utilisation. Therefore, a strategy to optimise provider performance is
      required. Performance scorecards are used by institutions for the purposes of
      driving quality improvement. There is no widely accepted or standardised
      scorecard that has been used for overall CCM performance. We aim to improve
      quality of care, patient safety and patient/family experience in CCM practice
      through the utilisation of a standardised, repeatable and multidimensional
      performance scorecard, designed to provide a continuous review of ICU physician
      and nurse practice, as well as departmental metrics. METHODS AND ANALYSIS: This
      will be a mixed-methods, controlled before and after study to assess the impact
      of a CCM-specific quality scorecard. Scorecard metrics were developed through
      expert consensus and existing literature. The study will include 19 attending CCM
      physicians and approximately 300 CCM nurses. Patient data for scorecard
      compilation are collected daily from bedside flow sheets. Preintervention
      baseline data will be collected for 6 months for each participant. After this,
      each participant will receive their scorecard measures. Following a 3-month
      washout period, postintervention data will be collected for 6 months. The primary
      outcome will be change in performance metrics following the provision of
      scorecard feedback to subjects. A cost analysis will also be performed, with the
      purpose of comparing total ICU costs prior to implementation of the scorecard
      with total ICU costs following implementation of the scorecard. The qualitative
      portion will include interviews with participants following the intervention
      phase. Interviews will be analysed in order to identify recurrent themes and
      subthemes, for the purposes of driving scorecard improvement. ETHICS AND
      DISSEMINATION: This protocol has been approved by the local research ethics
      board. Publication of results is anticipated in 2019. If this intervention is
      found to improve patient- and unit-directed outcomes, with evidence of cost
      effectiveness, it would support the utilisation of such a scorecard as a quality
      standard in CCM.

PMID- 29358444
TI  - Home-based exercise therapy in patients awaiting liver transplantation: protocol
      for an observational feasibility trial.
AB  - INTRODUCTION: Liver disease is the third most common cause of premature mortality
      in the UK. Liver failure accelerates frailty, resulting in skeletal muscle
      atrophy, functional decline and an associated risk of liver transplant waiting
      list mortality. However, there is limited research investigating the impact of
      exercise on patient outcomes pre and post liver transplantation. The waitlist
      period for patients listed for liver transplantation provides a unique
      opportunity to provide and assess interventions such as prehabilitation. METHODS
      AND ANALYSIS: This study is a phase I observational study evaluating the
      feasibility of conducting a randomised control trial (RCT) investigating the use
      of a home-based exercise programme (HBEP) in the management of patients awaiting
      liver transplantation. Twenty eligible patients will be randomly selected from
      the Queen Elizabeth University Hospital Birmingham liver transplant waiting list.
      Participants will be provided with an individually tailored 12-week HBEP,
      including step targets and resistance exercises. Activity trackers and patient
      diaries will be provided to support data collection. For the initial 6 weeks,
      telephone support will be given to discuss compliance with the study
      intervention, achievement of weekly targets, and to address any queries or
      concerns regarding the intervention. During weeks 6-12, participants will
      continue the intervention without telephone support to evaluate longer term
      adherence to the study intervention. On completing the intervention, all
      participants will be invited to engage in a focus group to discuss their
      experiences and the feasibility of an RCT. ETHICS AND DISSEMINATION: The protocol
      is approved by the National Research Ethics Service Committee North West -
      Greater Manchester East and Health Research Authority (REC reference:
      17/NW/0120). Recruitment into the study started in April 2017 and ended in July
      2017. Follow-up of participants is ongoing and due to finish by the end of 2017.
      The findings of this study will be disseminated through peer-reviewed
      publications and international presentations. In addition, the protocol will be
      placed on the British Liver Trust website for public access. TRIAL REGISTRATION
      NUMBER: NCT02949505; Pre-results.

PMID- 29358445
TI  - Online versus paper-based screening for depression and anxiety in adults with
      cystic fibrosis in Ireland: a cross-sectional exploratory study.
AB  - OBJECTIVE: To compare online and paper-based screening for depression and anxiety
      in adults with cystic fibrosis (CF). DESIGN AND SETTING: Cross-sectional study in
      CF clinics in Ireland and through the Cystic Fibrosis Ireland online community.
      PARTICIPANTS: 160 adult patients aged 18 or above were recruited. Of these, 147
      were included in the analysis; 83 online and 64 paper-based. The remaining 13
      were excluded because of incomplete data. MEASURES: Depression and anxiety were
      measured using the Hospital Anxiety and Depression Scale (HADS). Data on
      pulmonary function (forced expiratory volume in 1 s %) and body mass index were
      self-reported based on clinical assessments. Sociodemographic data were
      collected. RESULTS: Compared with the paper-based participants, the online
      participants were more likely to be female (61.7% vs 48.4%), older (mean 32.2 vs
      28.2 years) and were more likely to be married (32.5% vs 15.6%), living with
      their spouse or partner (42.5% vs 22.6%) and working either full time (33.7% vs
      15.9%) or part time (30.1%vs 17.5%). The prevalence rates of elevated anxiety and
      depression were not significantly different (P=0.71 and P=0.56). HADS anxiety and
      depression scores were not statistically different between online (P=0.83) and
      paper-based (P=0.92) participants based on Mann-Whitney U test. A significant
      negative correlation was found between depression and pulmonary function (r=
      0.39, P=0.01) and anxiety and pulmonary function (r=-0.36, P=0.02). Based on
      Cronbach's alpha, there were no statistically significant differences between the
      online and paper-based participants on the internal consistency of the HADS
      anxiety (P=0.073) and depression (P=0.378) scales. CONCLUSIONS: Our findings
      suggest that online and paper-based screening for depression and anxiety in adult
      patients with CF yield comparable findings on prevalence rates and scores,
      associations with health and internal consistency of subscales. This study
      highlights that online screening offers an alternative method to paper-based
      screening. Further research with a larger sample and assessment of measurement
      equivalence between online and paper based screening is needed to confirm our
      results.

PMID- 29358446
TI  - Assessing the impact of the National Department of Health's National Adherence
      Guidelines for Chronic Diseases in South Africa using routinely collected data: a
      cluster-randomised evaluation.
AB  - INTRODUCTION: In 2016, South Africa's National Department of Health (NDOH)
      launched the National Adherence Guidelines for Chronic Diseases for phased
      implementation throughout South Africa. Early implementation of a 'minimum
      package' of eight interventions in the Adherence Guidelines for patients with HIV
      is being undertaken at 12 primary health clinics and community health centres in
      four provinces. NDOH and its partners are evaluating the impact of five of the
      interventions in four provinces in South Africa. METHODS AND ANALYSIS: The
      minimum package is being delivered at the 12 health facilities under NDOH
      guidance and through local health authorities. The five evaluation interventions
      are: (1) fast track initiation counselling for patients eligible for
      antiretroviral therapy (ART); (2) adherence clubs for stable ART patients; (3)
      decentralised medication delivery for stable ART patients; (4) enhanced adherence
      counselling for unstable ART patients; and (5) early tracing of patients who miss
      an appointment by >=5 days. For evaluation, NDOH matched the 12 intervention
      clinics with 12 comparison clinics and randomly allocated one member of each pair
      to intervention or comparison (standard of care) status within pairs, allowing
      evaluation of the interventions using a matched cluster-randomised design. The
      evaluation uses data routinely collected by the clinics, with no study
      interaction with subjects to prevent influencing the primary outcomes. Enrolment
      began on 20 June 2016 and was completed on 16 December 2016. A total of 3456
      patients were enrolled and will now be followed for 14 months to estimate effects
      on short-term and final outcomes. Primary outcomes include viral suppression,
      retention and medication pickups, evaluated at two time points during follow-up.
      ETHICS AND DISSEMINATION: The study received approval from the University of
      Witwatersrand Human Research Ethics Committee and Boston University Institutional
      Review Board. Results will be presented to key stakeholders and at international
      conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER:
      NCT02536768; Pre-results.

PMID- 29358447
TI  - Engaging older people in an internet platform for cardiovascular risk self
      management: a qualitative study among Dutch HATICE participants.
AB  - OBJECTIVES: To study older peoples' experiences with an interactive internet
      platform for cardiovascular self-management, to assess which factors influence
      initial and sustained engagement. To assess their views on future use within
      primary care. DESIGN: Qualitative semistructured interview study, with thematic
      analysis. SETTING: Primary care in the Netherlands. PARTICIPANTS: People >=65
      years with an increased risk of cardiovascular disease who used the 'Healthy
      Ageing Through Internet Counselling in the Elderly' internet platform with remote
      support of a coach. Participants were selected using a purposive sampling method
      based on gender, age, level of education, cardiovascular history, diabetes,
      duration of participation and login frequency. RESULTS: We performed 17
      interviews with 20 participants, including three couples. In the initial phase,
      platform engagement was influenced by perceived computer literacy of the
      participants, user-friendliness, acceptability and appropriateness of the
      intervention and the initial interaction with the coach. Sustained platform use
      was mainly facilitated by a relationship of trust with the coach. Other
      facilitating factors were regular automatic and personal reminders, clear
      expectations of the platform, incorporation into daily routine, social support
      and a loyal and persistent attitude. Perceived lack of change in content of the
      platform could work both stimulating and discouraging. Participants supported the
      idea of embedding the platform into the primary care setting. CONCLUSIONS: Human
      support is crucial to initial and sustained engagement of older people in using
      an interactive internet platform for cardiovascular self-management. Regular
      reminders further facilitate sustained use, and increased tailoring to personal
      preference is recommended. Embedding the platform in primary healthcare may
      enhance future adoption. TRIAL REGISTRATION NUMBER: ISRCTN48151589; Pre-results.

PMID- 29358448
TI  - Investigating the application of motion accelerometers as a sleep monitoring
      technique and the clinical burden of the intensive care environment on sleep
      quality: study protocol for a prospective observational study in Australia.
AB  - INTRODUCTION: Sleep is a state of quiescence that facilitates the significant
      restorative processes that enhance individuals' physiological and psychological
      well-being. Patients admitted to the intensive care unit (ICU) experience
      substantial sleep disturbance. Despite the biological importance of sleep, sleep
      monitoring does not form part of standard clinical care for critically ill
      patients. There exists an unmet need to assess the feasibility and accuracy of a
      range of sleep assessment techniques that have the potential to allow widespread
      implementation of sleep monitoring in the ICU. KEY MEASURES: The coprimary
      outcome measures of this study are to: determine the accuracy and feasibility of
      motion accelerometer monitoring (ie, actigraphy) and subjective assessments of
      sleep (nursing-based observations and patient self-reports) to the gold standard
      of sleep monitoring (ie, polysomnography) in evaluating sleep continuity and
      disturbance. The secondary outcome measures of the study will include: (1) the
      association between sleep disturbance and environmental factors (eg, noise, light
      and clinical interactions) and (2) to describe the sleep architecture of
      intensive care patients. METHODS AND ANALYSIS: A prospective, single centre
      observational design with a within subjects' assessment of sleep monitoring
      techniques. The sample will comprise 80 adults (aged 18 years or more) inclusive
      of ventilated and non-ventilated patients, admitted to a tertiary ICU with a
      Richmond Agitation-Sedation Scale score between +2 (agitated) and -3 (moderate
      sedation) and an anticipated length of stay >24 hours. Patients' sleep quality,
      total sleep time and sleep fragmentations will be continuously monitored for 24
      hours using polysomnography and actigraphy. Behavioural assessments (nursing
      observations) and patients' self-reports of sleep quality will be assessed during
      the 24-hour period using the Richards-Campbell Sleep Questionnaire, subjective
      sleepiness evaluated via the Karolinska Sleepiness Scale, along with a
      prehospital discharge survey regarding patients' perception of sleep quality and
      disturbing factors using the Little Sleep Questionnaire will be undertaken.
      Associations between sleep disturbance, noise and light levels, and the frequency
      of clinical interactions will also be investigated. Sound and luminance levels
      will be recorded at 1 s epochs via Extech SDL600 and SDL400 monitoring devices.
      Clinical interactions will be logged via the electronic patient record system
      Metavision which documents patient monitoring and clinical care. ETHICS AND
      DISSEMINATION: The relevant institutions have approved the study protocol and
      consent procedures. The findings of the study will contribute to the
      understanding of sleep disturbance, and the ability to implement sleep monitoring
      methods within ICUs. Understanding the contribution of a clinical environment on
      sleep disturbance may provide insight into the need to address clinical
      environmental issues that may positively influence patient outcomes, and could
      dispel notions that the environment is a primary factor in sleep disturbance. The
      research findings will be disseminated via presentations at national and
      international conferences, proceedings and published articles in peer-reviewed
      journals. TRIAL REGISTRATION NUMBER: ACTRN12615000945527; Pre-results.

PMID- 29358449
TI  - Roles of mothers and fathers in supporting child physical activity: a cross
      sectional mixed-methods study.
AB  - OBJECTIVES: Examine the extent that parent gender is associated with supporting
      children's physical activity. DESIGN: Cross-sectional mixed-methods study.
      SETTING: 47 primary schools located in Bristol (UK). PARTICIPANTS: 944 children
      aged 8-9 years and one of their parents provided quantitative data; 51 parents
      (20 fathers) were interviewed. METHODS: Children wore an accelerometer, and mean
      minutes of moderate-to-vigorous physical activity (MVPA) per day, counts per
      minute (CPM) and achievement of national MVPA guidelines were derived. Parents
      reported who leads in supporting child activity during the week and weekend.
      Linear and logistic regression examined the association between gender of parent
      who supports child activity and child physical activity. For the semistructured
      telephone interviews, inductive and deductive content analyses were used to
      explore the role of gender in how parents support child activity. RESULTS:
      Parents appeared to have a stronger role in supporting boys to be more active,
      than girls, and the strongest associations were when they reported that both
      parents had equal roles in supporting their child. For example, compared with the
      reference of female/mother support, equal contribution from both parents during
      the week was associated with boys doing 5.9 (95% CI 1.2 to 10.6) more minutes of
      MVPA per day and more CPM when both parents support on weekday and weekends (55.1
      (14.3 to 95.9) and 52.8 (1.8 to 103.7), respectively). Associations in girls were
      weaker and sometimes in the opposite direction, but there was no strong
      statistical evidence for gender interactions. Themes emerged from the qualitative
      data, specifically; parents proactively supporting physical activity equally,
      mothers supporting during the week, families getting together at weekends,
      families doing activities separately due to preferences and parents using
      activities to bond one-to-one with children. CONCLUSIONS: Mothers primarily
      support child activity during the week. Children, possibly more so boys, are more
      active if both parents share the supporting role.

PMID- 29358452
TI  - Correction: Do psychological harms result from being labelled with an unexpected
      diagnosis of abdominal aortic aneurysm or prostate cancer through screening? A
      systematic review.

PMID- 29358450
TI  - Screening for chronic kidney disease in a community-based diabetes cohort in
      rural Guatemala: a cross-sectional study.
AB  - OBJECTIVE: Screening is a key strategy to address the rising burden of chronic
      kidney disease (CKD) in low-income and middle-income countries. However, there
      are few reports regarding the implementation of screening programmes in resource
      limited settings. The objectives of this study are to (1) to share programmatic
      experiences implementing CKD screening in a rural, resource-limited setting and
      (2) to assess the burden of renal disease in a community-based diabetes programme
      in rural Guatemala. DESIGN: Cross-sectional assessment of glomerular filtration
      rate (GFR) and urine albumin. SETTING: Central Highlands of Guatemala.
      PARTICIPANTS: We enrolled 144 adults with type 2 diabetes in a community-based
      CKD screening activity carried out by the sponsoring institution. OUTCOME
      MEASURES: Prevalence of renal disease and risk of CKD progression using Kidney
      Disease: Improving Global Outcomes definitions and classifications. RESULTS: We
      found that 57% of the sample met GFR and/or albuminuria criteria suggestive of
      CKD. Over half of the sample had moderate or greater increased risk for CKD
      progression, including nearly 20% who were classified as high or very high risk.
      Hypertension was common in the sample (42%), and glycaemic control was suboptimal
      (mean haemoglobin A1c 9.4%+/-2.5% at programme enrolment and 8.6%+/-2.3% at time
      of CKD screening). CONCLUSIONS: The high burden of renal disease in our patient
      sample suggests an imperative to better understand the burden and risk factors of
      CKD in Guatemala. The implementation details we share reveal the tension between
      evidence-based CKD screening versus screening that can feasibly be delivered in
      resource-limited global settings.

PMID- 29358453
TI  - Correction: Selecting pH cut-offs for the safe verification of nasogastric
      feeding tube placement: a decision analytical modelling approach.

PMID- 29358451
TI  - Comparative efficacy and acceptability of interventions for major depression in
      older persons: protocol for Bayesian network meta-analysis.
AB  - INTRODUCTION: Major depression is a leading cause of disability and has been
      associated with adverse effects in older persons. While many pharmacological and
      non-pharmacological interventions have been shown to be effective to address
      major depression in older persons, there has not been a meta-analysis that
      consolidates all the available interventions and compare the relative benefits of
      these available interventions. In this study, we aim to conduct a systematic
      review and network meta-analysis to compare the efficacy and acceptability of all
      the known pharmacological and non-pharmacological interventions for major
      depression in older persons. METHODS AND ANALYSIS: We will search Medline,
      Embase, PsycINFO, Cumulative Index to Nursing and Allied Health, Cochrane Central
      Register of Controlled Trials and references of other review articles for
      articles related to the keywords of 'randomised trial', 'major depression',
      'older persons' and 'treatments'. Two reviewers will independently select the
      eligible articles. For each included article, the two reviewers will
      independently extract the data and assess the risk of bias using the Cochrane
      revised tool for risk of bias. Bayesian network meta-analyses will be conducted
      to pool the depression scores (based on standardised mean difference) and the all
      cause discontinuation across all included studies. The ranking probabilities for
      all interventions will be estimated and the hierarchy of each intervention will
      be summarised as surface under the cumulative ranking curve (SUCRA). Meta
      regression and sub-group analyses will also be performed to evaluate the effect
      of study-level covariates. The quality of the evidence will be assessed using the
      Grading of Recommendations Assessment, Development and Evaluation approach.
      ETHICS AND DISSEMINATION: The results will be disseminated through conference
      presentations and peer-reviewed publications. They will provide the consolidated
      evidence to inform clinicians on the best choice of intervention to address major
      depression in older persons. PROSPERO REGISTRATION NUMBER: CRD42017075756.

PMID- 29358454
TI  - Correction: Design and rationale of the Cardiovascular Health and Text Messaging
      (CHAT) Study and the CHAT-Diabetes Mellitus (CHAT-DM) Study: two randomised
      controlled trials of text messaging to improve secondary prevention for coronary
      heart disease and diabetes.

PMID- 29358455
TI  - Correction: Low-dose glucocorticoids plus rituximab versus high-dose
      glucocorticoids plus rituximab for remission induction in ANCA-associated
      vasculitis (LoVAS): protocol for a multicentre, open-label, randomised controlled
      trial.

PMID- 29358456
TI  - Does Chronic Obstructive Pulmonary Disease Cause Cardiovascular Disease?

PMID- 29358457
TI  - Primary Aldosteronism and Cardiovascular Events: It Is Time to Take Guideline
      Recommendations Seriously.

PMID- 29358459
TI  - Determinants of Cardiometabolic Risk Factors in the First Decade of Life: A
      Longitudinal Study Starting at Birth.
AB  - The present prospective study assessed the association of birth weight (BW) and
      growth pattern on cardiometabolic risk factors in a cohort followed from birth to
      10 years of age. One hundred and forty-five subjects (73 girls) who fulfilled the
      inclusion criteria and had all their data recorded at birth and at 5 years were
      enrolled. Of these, 100 (52 girls) also recorded data at 10 years. Anthropometric
      measurements, office and 24-hour blood pressure, and metabolic parameters were
      obtained. At 5 years, both BW and current weight were determinants of blood
      pressure and metabolic parameters; however, as the subjects got older, the impact
      of body size increased. Higher BW and maternal obesity increased the risk of
      becoming obese at 5 years while this was reduced if breastfeeding. Maternal
      obesity was the only factor associated with becoming obese at 10 years. Twenty
      two children at 10 years had insulin values >=15 U/L, some of whom were
      persistent from 5 years while in others it increased afterward. Subjects with
      insulin values >=15 U/L showed significant higher values of office systolic blood
      pressure, triglycerides, and uric acid and lower values of high-density
      lipoprotein than did those with normal insulin values. Highest weight gain from 5
      to 10 years and lowest BW were the main determinants of high insulin levels. In
      conclusion, although BW was a proxy of the events during fetal life and projected
      its influence later, the influence of gaining weight was a key determinant in the
      risk to develop obesity and metabolic abnormalities.

PMID- 29358458
TI  - Surrogate Markers of Cardiovascular Risk and Chronic Obstructive Pulmonary
      Disease: A Large Case-Controlled Study.
AB  - Cardiovascular disease is a common comorbidity and cause of mortality in chronic
      obstructive pulmonary disease. A better understanding of mechanisms of
      cardiovascular risk in chronic obstructive pulmonary disease patients is needed
      to improve clinical outcomes. We hypothesized that such patients have increased
      arterial stiffness, wave reflections, and subclinical atherosclerosis compared
      with controls and that these findings would be independent of smoking status and
      other confounding factors. A total of 458 patients with a diagnosis of chronic
      obstructive pulmonary disease and 1657 controls (43% were current or ex-smokers)
      with no airflow limitation were matched for age, sex, and body mass index. All
      individuals underwent assessments of carotid-femoral (aortic) pulse wave
      velocity, augmentation index, and carotid intima-media thickness. The mean age of
      the cohort was 67+/-8 years and 58% were men. Patients with chronic obstructive
      pulmonary disease had increased aortic pulse wave velocity (9.95+/-2.54 versus
      9.27+/-2.41 m/s; P<0.001), augmentation index (28+/-10% versus 25+/-10%;
      P<0.001), and carotid intima-media thickness (0.83+/-0.19 versus 0.74+/-0.14 mm;
      P<0.001) compared with controls. Chronic obstructive pulmonary disease was
      associated with increased levels of each vascular biomarker independently of
      physiological confounders, smoking, and other cardiovascular risk factors. In
      this large case-controlled study, chronic obstructive pulmonary disease was
      associated with increased arterial stiffness, wave reflections, and subclinical
      atherosclerosis, independently of traditional cardiovascular risk factors. These
      findings suggest that the cardiovascular burden observed in this condition may be
      mediated through these mechanisms and supports the concept that chronic
      obstructive pulmonary disease is an independent risk factor for cardiovascular
      disease.

PMID- 29358462
TI  - In This Issue of Diabetes Care.

PMID- 29358460
TI  - Prevalence of Cardiovascular Disease and Its Risk Factors in Primary
      Aldosteronism: A Multicenter Study in Japan.
AB  - There have been several clinical studies examining the factors associated with
      cardiovascular disease (CVD) in patients with primary aldosteronism (PA);
      however, their results have left it unclear whether CVD is affected by the plasma
      aldosterone concentration or hypokalemia. We assessed the PA database established
      by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the
      prevalence of CVD among patients with PA with that among age-, sex-, and blood
      pressure-matched essential hypertension patients and participants with
      hypertension in a general population cohort. We also performed binary logistic
      regression analysis to determine which parameters significantly increased the
      odds ratio for CVD. Of the 2582 patients with PA studied, the prevalence of CVD,
      including stroke (cerebral infarction, cerebral hemorrhage, or subarachnoid
      hemorrhage), ischemic heart disease (myocardial infarction or angina pectoris),
      and heart failure, was 9.4% (stroke, 7.4%; ischemic heart disease, 2.1%; and
      heart failure, 0.6%). The prevalence of CVD, especially stroke, was higher among
      the patients with PA than those with essential hypertension/hypertension.
      Hypokalemia (K+ <=3.5 mEq/L) and the unilateral subtype significantly increased
      adjusted odds ratios for CVD. Although aldosterone levels were not linearly
      related to the adjusted odds ratio for CVD, patients with plasma aldosterone
      concentrations >=125 pg/mL had significantly higher adjusted odds ratios for CVD
      than those with plasma aldosterone concentrations <125 pg/mL. Thus, patients with
      PA seem to be at a higher risk of developing CVD than patients with essential
      hypertension. Moreover, patients with PA presenting with hypokalemia, the
      unilateral subtype, or plasma aldosterone concentration >=125 pg/mL are at a
      greater risk of CVD and have a greater need for PA-specific treatments than
      others.

PMID- 29358461
TI  - STIM2 (Stromal Interaction Molecule 2)-Mediated Increase in Resting Cytosolic
      Free Ca2+ Concentration Stimulates PASMC Proliferation in Pulmonary Arterial
      Hypertension.
AB  - An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery
      smooth muscle cells (PASMCs) triggers pulmonary vasoconstriction and stimulates
      PASMC proliferation leading to vascular wall thickening. Here, we report that
      STIM2 (stromal interaction molecule 2), a Ca2+ sensor in the sarcoplasmic
      reticulum membrane, is required for raising the resting [Ca2+]cyt in PASMCs from
      patients with pulmonary arterial hypertension (PAH) and activating signaling
      cascades that stimulate PASMC proliferation and inhibit PASMC apoptosis.
      Downregulation of STIM2 in PAH-PASMCs reduces the resting [Ca2+]cyt, whereas
      overexpression of STIM2 in normal PASMCs increases the resting [Ca2+]cyt The
      increased resting [Ca2+]cyt in PAH-PASMCs is associated with enhanced
      phosphorylation (p) of CREB (cAMP response element-binding protein), STAT3
      (signal transducer and activator of transcription 3), and AKT, increased NFAT
      (nuclear factor of activated T-cell) nuclear translocation, and elevated level of
      Ki67 (a marker of cell proliferation). Furthermore, the STIM2-associated increase
      in the resting [Ca2+]cyt also upregulates the antiapoptotic protein Bcl-2 in PAH
      PASMCs. Downregulation of STIM2 in PAH-PASMCs with siRNA (1) decreases the level
      of pCREB, pSTAT3, and pAKT and inhibits NFAT nuclear translocation, thereby
      attenuating proliferation, and (2) decreases Bcl-2, which leads to an increase of
      apoptosis. In summary, these data indicate that upregulated STIM2 in PAH-PASMCs,
      by raising the resting [Ca2+]cyt, contributes to enhancing PASMC proliferation by
      activating the CREB, STAT3, AKT, and NFAT signaling pathways and stimulating
      PASMC proliferation. The STIM2-associated increase in the resting [Ca2+]cyt is
      also involved in upregulating Bcl-2 that makes PAH-PASMCs resistant to apoptosis,
      and thus plays an important role in sustained pulmonary vasoconstriction and
      excessive pulmonary vascular remodeling in patients with PAH.

PMID- 29358463
TI  - The National Diabetes Education Program at 20 Years: Lessons Learned and Plans
      for the Future.
AB  - The National Diabetes Education Program (NDEP) was established to translate
      findings from diabetes research studies into clinical and public health practice.
      Over 20 years, NDEP has built a program with partnership engagement that includes
      science-based resources for multiple population and stakeholder audiences.
      Throughout its history, NDEP has developed strategies and messages based on
      communication research and relied on established behavior change models from
      health education, communication, and social marketing. The program's success in
      continuing to engage diverse partners after 20 years has led to time-proven and
      high-quality resources that have been sustained. Today, NDEP maintains a national
      repository of diabetes education tools and resources that are high quality,
      science- and audience-based, culturally and linguistically appropriate, and
      available free of charge to a wide variety of audiences. This review looks back
      and describes NDEP's evolution in transforming and communicating diabetes
      management and type 2 diabetes prevention strategies through partnerships,
      campaigns, educational resources, and tools and identifies future opportunities
      and plans.

PMID- 29358464
TI  - Mortality Reduction in EMPA-REG OUTCOME Trial: Beyond the Antidiabetes Effect.
AB  - Two recent large-scale cardiovascular outcome trials, a now common tool in
      assessing the safety of pharmacological treatments for type 2 diabetes, reported
      significant reductions in all-cause mortality. In EMPA-REG OUTCOME [BI 10773
      (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus
      Patients], patients who received the SGLT2 inhibitor empagliflozin had a notable
      reduction of 9.2 deaths per 1,000 per year, while LEADER (Liraglutide Effect and
      Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term
      Evaluation) found that the patients receiving the GLP-1 receptor agonist
      liraglutide had a reduction of 3.7 deaths per 1,000 per year. The hypotheses to
      explain the sizable mortality reduction in EMPA-REG OUTCOME have mainly focused
      on the potential cardiovascular mechanisms of empagliflozin, but none considered
      its expected antidiabetes effects. I estimated the portion of the reduction in
      mortality observed in EMPA-REG OUTCOME expected to be a result of its
      antidiabetes effects, as measured by glycemic control and the need for additional
      antidiabetes medication, and contrasted it with LEADER. With use of the mean
      0.45% reduction in HbA1c with empagliflozin compared with placebo in EMPA-REG
      OUTCOME, the rate reduction of 9.2 deaths per 1,000 per year would be expected to
      be at most 4.5 deaths per 1,000 per year, leaving 4.7 deaths per 1,000 per year
      otherwise explained. On the other hand, LEADER's rate reduction of 3.7 deaths per
      1,000 per year with liraglutide would be expected to be 3.5 by virtue of its
      effect on HbA1c, leaving 0.2 deaths per 1,000 per year explained otherwise.
      Similar results were found using the need for additional antidiabetes treatment
      during follow-up to measure the antidiabetes impact. In conclusion, the expected
      antidiabetes effects of empagliflozin and liraglutide on the reduction in
      mortality are important. However, empagliflozin appears to have significant
      additional effects on survival, possibly due to specific cardiovascular
      mechanisms, which merit further investigation.

PMID- 29358465
TI  - Teasing Diabetes Apart, One Locus at a Time.

PMID- 29358466
TI  - Discovery, Knowledge, and Action-Diabetes in Pregnancy Across the Translational
      Spectrum: The 2016 Norbert Freinkel Award Lecture.
AB  - The Norbert Freinkel Award is given in memory of Norbert Freinkel, a dedicated
      and insightful investigator and gifted writer, to honor a researcher who has made
      outstanding contributions, including scientific publications and presentations,
      to the understanding and treatment of diabetes in pregnancy. H. David McIntyre,
      MD, FRACP, Director of Obstetric Medicine at Mater Health Services and Head of
      the Mater Clinical Unit at The University of Queensland in Brisbane, Australia,
      received the prestigious award at the American Diabetes Association's 76th
      Scientific Sessions, 10-14 June 2016, in New Orleans, LA. He presented the
      Norbert Freinkel Award Lecture, "Discovery, Knowledge, and Action-Diabetes in
      Pregnancy Across the Translational Spectrum," on Saturday, 11 June 2016.

PMID- 29358468
TI  - The Role of Diabetes Care and Its Contributions to the Field of Diabetes: A
      Profile in Progress.

PMID- 29358467
TI  - Diabetes in Youth-Looking Backwards to Inform the Future: Kelly West Award
      Lecture 2017.
AB  - The Kelly West Award for Outstanding Achievement in Epidemiology is presented in
      honor of the memory of Kelly M. West, widely regarded as the "father of diabetes
      epidemiology." Harry Keen described West as characterized by "generosity of
      spirit, deeply human and humorous, deliberate of address, modest, conciliatory
      and untiringly persevering. Few people have done so much to change the landscape
      of diabetes" (1). The award and lecture recognize a leading epidemiologist in the
      field of diabetes. Dana Dabelea, MD, PhD, received this award at the American
      Diabetes Association's 77th Scientific Sessions, 9-13 June 2017, in San Diego,
      CA. She presented the Kelly West Award Lecture, "Diabetes in Youth-Looking
      Backwards to Inform the Future," on Sunday, 11 June 2017.

PMID- 29358469
TI  - Nonalcoholic Fatty Liver Disease and Risk of Incident Type 2 Diabetes: A Meta
      analysis.
AB  - OBJECTIVE: Several studies have explored the impact of nonalcoholic fatty liver
      disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which
      NAFLD may confer risk of incident diabetes remains uncertain. We performed a meta
      analysis of relevant studies to quantify the magnitude of the association between
      NAFLD and risk of incident diabetes. RESEARCH DESIGN AND METHODS: We collected
      data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We
      included only large (n >=500) observational studies with a follow-up duration of
      at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies
      were selected according to predefined keywords and clinical outcomes. Data from
      selected studies were extracted, and meta-analysis was performed using random
      effects modeling. RESULTS: A total of 19 observational studies with 296,439
      individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over
      a median of 5 years were included in the final analysis. Patients with NAFLD had
      a greater risk of incident diabetes than those without NAFLD (random-effects
      hazard ratio [HR] 2.22, 95% CI 1.84-2.60; I2 = 79.2%). Patients with more
      "severe" NAFLD were also more likely to develop incident diabetes; this risk
      increased across the ultrasonographic scores of steatosis (n = 3 studies), but it
      appeared to be even greater among NAFLD patients with advanced high NAFLD
      fibrosis score (n = 1 study; random-effects HR 4.74, 95% CI 3.54-5.94).
      Sensitivity analyses did not alter these findings. Funnel plot and Egger test did
      not reveal significant publication bias. Study limitations included high
      heterogeneity, varying degrees of confounder adjustment across individual
      studies, and lack of studies using liver biopsy. CONCLUSIONS: NAFLD is
      significantly associated with a twofold increased risk of incident diabetes.
      However, the observational design of the eligible studies does not allow for
      proving causality.

PMID- 29358471
TI  - Comment on Edelman and Polonsky. Type 2 Diabetes in the Real World: The Elusive
      Nature of Glycemic Control. Diabetes Care 2017;40:1425-1432.

PMID- 29358472
TI  - Response to Comment on Edelman and Polonsky. Type 2 Diabetes in the Real World:
      The Elusive Nature of Glycemic Control. Diabetes Care 2017;40:1425-1432.

PMID- 29358473
TI  - Comment on Lent et al. All-Cause and Specific-Cause Mortality Risk After Roux-en
      Y Gastric Bypass in Patients With and Without Diabetes. Diabetes Care
      2017;40:1379-1385.

PMID- 29358474
TI  - Response to comment on Lent et al. All-Cause and Specific-Cause Mortality Risk
      After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes. Diabetes
      Care 2017;40:1379-1385.

PMID- 29358475
TI  - Treat suspected flu with antivirals, hospital doctors are told.

PMID- 29358476
TI  - Tumours composed of fat are no longer a simple diagnosis: an overview of fatty
      tumours with a spindle cell component.
AB  - This is a review of the morphological spectrum of fatty tumours containing a
      component of spindle cells, highlighting the immunohistochemical and cytogenetic
      workup that is now mandatory for accurate diagnosis, with the goal of providing a
      practical approach for practising surgical pathologists. There have been
      significant advances in recent years in classifying and understanding the
      pathogenesis of fatty tumours with spindle cells, based on the correlation of
      histological, immunohistochemical and cytogenetic/molecular findings. In spite of
      this, morphological diagnosis and accurate classification of fatty tumours with
      spindle cells can be challenging to diagnostic pathologists. A group of three
      lesions: spindle cell lipoma, mammary-type myofibroblastoma and cellular
      angiofibroma share morphological features and are united by retinoblastoma
      protein (pRb) loss. Closely allied to these lesions, especially spindle cell
      lipoma is the newly designated atypical spindle cell lipomatous tumour, which
      shares morphological, immunohistochemical and cytogenetic features with the trio
      of tumours lacking nuclear pRb. All of these lesions lack MDM2 and CDK4
      amplification as well and separation is based on clinical features, principally
      location. Atypical lipomatous tumour or well-differentiated liposarcoma shows
      retention of pRb but overexpression and amplification of MDM2. Fatty tumours with
      spindle cells need to be extensively sampled, with careful attention paid to
      cellular atypia and location, and they need to have immunohistochemical workup
      with pRb, MDM2, desmin, CD34 and p16. In addition, cytogenetic analysis for MDM2
      and CDK4 amplification has become crucial for the proper identification of these
      lesions.

PMID- 29358477
TI  - Aspergillus tamarii: an uncommon burn wound infection.

PMID- 29358480
TI  - From Strangers in a Foreign Land to Active, Engaged Citizens.

PMID- 29358479
TI  - Advocacy for Improving Nutrition in the First 1000 Days to Support Childhood
      Development and Adult Health.
AB  - Maternal prenatal nutrition and the child's nutrition in the first 2 years of
      life (1000 days) are crucial factors in a child's neurodevelopment and lifelong
      mental health. Child and adult health risks, including obesity, hypertension, and
      diabetes, may be programmed by nutritional status during this period. Calories
      are essential for growth of both fetus and child but are not sufficient for
      normal brain development. Although all nutrients are necessary for brain growth,
      key nutrients that support neurodevelopment include protein; zinc; iron; choline;
      folate; iodine; vitamins A, D, B6, and B12; and long-chain polyunsaturated fatty
      acids. Failure to provide key nutrients during this critical period of brain
      development may result in lifelong deficits in brain function despite subsequent
      nutrient repletion. Understanding the complex interplay of micro- and
      macronutrients and neurodevelopment is key to moving beyond simply recommending a
      "good diet" to optimizing nutrient delivery for the developing child. Leaders in
      pediatric health and policy makers must be aware of this research given its
      implications for public policy at the federal and state level. Pediatricians
      should refer to existing services for nutrition support for pregnant and
      breastfeeding women, infants, and toddlers. Finally, all providers caring for
      children can advocate for healthy diets for mothers, infants, and young children
      in the first 1000 days. Prioritizing public policies that ensure the provision of
      adequate nutrients and healthy eating during this crucial time would ensure that
      all children have an early foundation for optimal neurodevelopment, a key factor
      in long-term health.

PMID- 29358478
TI  - Identification of rare diseases by screening a population selected on the basis
      of routine pathology results-the PATHFINDER project: lysosomal acid
      lipase/cholesteryl ester storage disease substudy.
AB  - AIMS: Lysosomal acid lipase deficiency (LALD) is an autosomal recessive disorder
      of cholesterol ester storage associated with hepatic disease, cirrhosis and
      accelerated atherosclerosis. Its prevalence in the general population, patients
      with dyslipidaemia and raised transaminases is unclear. This study attempted to
      identify the prevalence of LALD from patients with abnormal results in laboratory
      databases. METHODS: Electronic laboratory databases were interrogated to identify
      from clinical biochemistry records patients with a phenotype of low high-density
      lipoprotein-cholesterol (<=0.85 mmol/L; 33 mg/dL) and with elevated alanine or
      aspartate transaminases (>=60 IU/L) on one occasion or more over a 3-year time
      interval. Patients were recalled, and a dried blood spot sample was collected for
      lysosomal acid lipase determination by a fluorimetric enzyme assay.
      Histopathology databases of liver biopsies were interrogated for patients with
      features of 'microvesicular cirrhosis' or 'cryptogenic cirrhosis' in the report.
      Histological blocks were sampled, and samples were analysed by next-generation
      sequencing for the presence of mutations in the LAL gene. RESULTS: Samples were
      obtained from 1825 patients with dyslipidaemia and elevated transaminases. No
      cases of LALD were identified. Liver biopsies were obtained from six patients.
      DNA extraction was successful from four patients. Two patients were homozygous
      for the LAL c.46A>C;p.Thr16Pro unclassified variant in exon 2. CONCLUSIONS:
      Pathology databases hold routine information that can be used to identify
      patients with specific patterns of results or those who had biopsies to allow
      targeted testing for possible causes of disease. Biochemical screening suggests
      that the gene frequency of LAL deficiency in adults is less than 1 in 100.

PMID- 29358481
TI  - Pediatricians and Public Health: Optimizing the Health and Well-Being of the
      Nation's Children.
AB  - Ensuring optimal health for children requires a population-based approach and
      collaboration between pediatrics and public health. The prevention of major
      threats to children's health (such as behavioral health issues) and the control
      and management of chronic diseases, obesity, injury, communicable diseases, and
      other problems cannot be managed solely in the pediatric office. The integration
      of clinical practice with public health actions is necessary for multiple levels
      of disease prevention that involve the child, family, and community. Although
      pediatricians and public health professionals interact frequently to the benefit
      of children and their families, increased integration of the 2 disciplines is
      critical to improving child health at the individual and population levels.
      Effective collaboration is necessary to ensure that population health activities
      include children and that the child health priorities of the American Academy of
      Pediatrics (AAP), such as poverty and child health, early brain and child
      development, obesity, and mental health, can engage federal, state, and local
      public health initiatives. In this policy statement, we build on the 2013 AAP
      Policy Statement on community pediatrics by identifying specific opportunities
      for collaboration between pediatricians and public health professionals that are
      likely to improve the health of children in communities. In the statement, we
      provide recommendations for pediatricians, public health professionals, and the
      AAP and its chapters.

PMID- 29358483
TI  - UK women launch legal action against Bayer over Essure sterilisation device.

PMID- 29358484
TI  - Sharing of patient data didn't breach rules, says public health agency.

PMID- 29358482
TI  - Unstable Housing and Caregiver and Child Health in Renter Families.
AB  - OBJECTIVES: To evaluate how 3 forms of housing instability relate to caregiver
      and child health among low-income renter households. METHODS: Caregivers of
      children 0 to 48 months of age were interviewed in 5 urban medical centers from
      May 2009 to December 2015. Caregivers reported on the following: caregiver
      health, maternal depressive symptoms, child's health, lifetime hospitalizations,
      developmental risk, and 3 housing circumstances, which were categorized as being
      behind on rent in the past 12 months, multiple moves (>= 2 in past 12 months),
      and child's lifetime history of homelessness. Associations with caregiver and
      child health outcomes were examined through multivariable logistic regression.
      RESULTS: Of 22 324 families, 34% had at least 1 of the following adverse housing
      circumstances: 27% had been behind on rent, 8% had made multiple moves, and 12%
      had a history of being homeless. Overlap between these was limited; 86%
      experienced only 1 adverse housing circumstance. Each circumstance was
      individually associated with increased adjusted odds of adverse health and
      material hardship compared with stable housing. Households behind on rent had
      increased adjusted odds of fair and/or poor caregiver health (adjusted odds ratio
      [aOR]: 1.91; 95% confidence interval [CI]: 1.77-2.05), maternal depressive
      symptoms (aOR: 2.71; 95% CI: 2.51-2.93), child lifetime hospitalizations (aOR:
      1.19; 95% CI: 1.10-1.27), fair and/or poor child health (aOR: 1.41; 95% CI: 1.28
      1.56), and household material hardships. Families with multiple moves and history
      of homelessness had similar adverse caregiver, child, health, and hardship
      outcomes. CONCLUSIONS: Three forms of housing instability were associated with
      adverse caregiver and child health among low-income renter households. The
      American Academy of Pediatrics recommends social screening within health care;
      providers could consider assessing for behind on rent, multiple moves, and
      homelessness in high-risk practices.

PMID- 29358485
TI  - In This Issue of Diabetes.

PMID- 29358486
TI  - Cellular Energy Sensing and Metabolism-Implications for Treating Diabetes: The
      2017 Outstanding Scientific Achievement Award Lecture.
AB  - The Outstanding Scientific Achievement Award recognizes distinguished scientific
      achievement in the field of diabetes, taking into consideration independence of
      thought and originality. Gregory R. Steinberg, PhD, professor of medicine, Canada
      Research Chair, J. Bruce Duncan Endowed Chair in Metabolic Diseases, and
      codirector of the Metabolism and Childhood Obesity Research Program at McMaster
      University, Hamilton, Ontario, Canada, received the prestigious award at the
      American Diabetes Association's 77th Scientific Sessions, 9-13 June 2017, in San
      Diego, CA. He presented the Outstanding Scientific Achievement Award Lecture,
      "Cellular Energy Sensing and Metabolism-Implications for Treating Diabetes," on
      Monday, 12 June 2017.The survival of all cells is dependent on the constant
      challenge to match energetic demands with nutrient availability, a task that is
      mediated through a highly conserved network of metabolic fuel sensors that
      orchestrate both cellular and whole-organism energy balance. A mismatch between
      cellular energy demand and nutrient availability is a key factor contributing to
      the development of type 2 diabetes; thus, understanding the fundamental
      mechanisms by which cells sense nutrient availability and demand may lead to the
      development of new treatments. Glucose-lowering therapies, such as caloric
      restriction, exercise, and metformin, all induce an energetic challenge that
      results in the activation of the cellular energy sensor AMP-activated protein
      kinase (AMPK). Activation of AMPK in turn suppresses lipid synthesis and
      inflammation while increasing glucose uptake, fatty acid oxidation, and
      mitochondrial function. In contrast, high levels of nutrient availability
      suppress AMPK activity while also increasing the production of peripheral
      serotonin, a gut-derived endocrine factor that suppresses beta-adrenergic-induced
      activation of brown adipose tissue. Identifying new ways to manipulate these two
      ancient fuel gauges by activating AMPK and inhibiting peripheral serotonin may
      lead to the development of new therapies for treating type 2 diabetes.

PMID- 29358487
TI  - "NO" to Autophagy: Fat Does the Trick for Diabetes.

PMID- 29358489
TI  - Test patients with rheumatoid arthritis for anti-CCP antibodies, says NICE.

PMID- 29358490
TI  - Understanding cardiac troponin part 2: early rule out of acute coronary syndrome.
AB  - Chest pain of suspected cardiac origin is a very common emergency department
      presentation. Over the past decade, there has been an exponential growth in
      strategies that promote blood sampling at earlier and earlier time points after
      presentation to facilitate the rule out of acute coronary syndrome.In part 2 of
      this series, we examine key concepts from the recent literature with the aim of
      improving clinicians' understanding of the rule-out strategies available to them
      and provide a structured overview of strategies that facilitate discharge with
      blood testing over <3 hours.

PMID- 29358492
TI  - NHS England faces legal challenges over proposed changes to services.

PMID- 29358491
TI  - Ketamine procedural sedation in the emergency department of an urban tertiary
      hospital in Dar es Salaam, Tanzania.
AB  - STUDY OBJECTIVE: We describe ketamine procedural sedations and associated adverse
      events in low-acuity and high-acuity patients in a resource-limited ED. METHODS:
      This was a prospective observational study of ketamine procedural sedations at
      the Emergency Medical Department at the Muhimbili National Hospital in Dar es
      Salaam, Tanzania. We observed consecutive procedural sedations and recorded
      patient demographics, medications, vital signs, pulse oximetry, capnography and a
      priori defined adverse events (using standard definitions in emergency medicine
      sedation guidelines). All treatment decisions were at the discretion of the
      treating providers who were blinded to study measurements to simulate usual care.
      Data collection was unblinded if predefined safety parameters were met. For all
      significant adverse and unblinding events, ketamine causality was determined via
      review protocol. Additionally, providers and patients were assessed for sedation
      satisfaction. RESULTS: We observed 54 children (median 3 years, range 11 days-15
      years) and 45 adults (median 33 years, range 18-79 years). The most common
      indications for ketamine were burn management in children (55.6%) and orthopaedic
      procedures in adults (68.9%). Minor adverse events included nausea/vomiting
      (12%), recovery excitation (11%) and one case of transient hypertension. There
      were nine (9%) patients who had decreased saturation readings (SpO2 <=92%). There
      were three deaths, all in severely injured patients. After review protocol, none
      of the desaturations or patient deaths were thought to be caused by ketamine. No
      patient experienced ketamine-related laryngospasm, apnoea or permanent
      complications. Overall, ketamine was well tolerated and resulted in high patient
      and provider satisfaction. CONCLUSION: In this series of ketamine sedations in an
      urban, resource-limited ED, there were no serious adverse events attributable to
      ketamine.

PMID- 29358493
TI  - Effects of Preceding Ethanol Intake on Glucose Response to Low-Dose Glucagon in
      Individuals With Type 1 Diabetes: A Randomized, Placebo-Controlled, Crossover
      Study.
AB  - OBJECTIVE: This study investigated whether preceding ethanol intake impairs
      glucose response to low-dose glucagon in individuals with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: This was a randomized, crossover, placebo-controlled
      study in 12 insulin pump-treated individuals (median [interquartile range] age,
      37 [31-51] years; HbA1c, 57 [51-59] mmol/mol or 7.3% [6.8-7.5]; and BMI, 23.9 [22
      25] kg/m2). During two overnight study visits, a 6 p.m. dinner (1 g
      carbohydrates/kg) was served with diet drink (placebo) or diet drink and ethanol
      (0.8 g/kg). After 8-9 h, ethanol was estimated to be metabolized, and a
      subcutaneous (s.c.) insulin bolus was given to induce mild hypoglycemia. When
      plasma glucose (PG) was <=3.9 mmol/L, 100 ug glucagon was given s.c., followed by
      another s.c. 100 ug glucagon 2 h later. Primary end point was incremental peak PG
      induced by the first glucagon bolus. RESULTS: Ethanol was undetectable before
      insulin administration at both visits. The insulin doses (mean +/- SEM: 2.5 +/-
      0.4 vs. 2.7 +/- 0.4 IU) to induce hypoglycemia (3.7 +/- 0.1 vs. 3.9 +/- 0.1
      mmol/L) did not differ and caused similar insulin levels (28.3 +/- 4.6 vs. 26.1
      +/- 4.0 mU/L) before glucagon administration on ethanol and placebo visits (all,
      P > 0.05). The first glucagon bolus tended to cause lower incremental peak PG
      (2.0 +/- 0.5 vs. 2.9 +/- 0.3 mmol/L, P = 0.06), lower incremental area under the
      curve (87 +/- 40 vs. 191 +/- 37 mmol/L * min, P = 0.08), and lower 2-h PG level
      (3.6 +/- 1.0 vs. 4.8 +/- 0.4 mmol/L, P = 0.05) after ethanol compared with
      placebo. The second glucagon bolus had similar responses between visits, but PG
      remained 1.8 +/- 0.7 mmol/L lower after ethanol compared with placebo.
      CONCLUSIONS: The ability of low-dose glucagon to treat mild hypoglycemia
      persisted with preceding ethanol intake, although it tended to be attenuated.

PMID- 29358494
TI  - Low-grade Inflammatory Marker Profile May Help to Differentiate Patients With
      LADA, Classic Adult-Onset Type 1 Diabetes, and Type 2 Diabetes.
AB  - OBJECTIVE: To test whether differences in serum concentrations of adiposity
      related low-grade inflammatory mediators could help to differentiate patients
      with latent autoimmune diabetes in adults (LADA), classic adult-onset type 1
      diabetes, and type 2 diabetes. RESEARCH DESIGN AND METHODS: This cross-sectional
      study involved 75 patients with LADA, 67 with classic adult-onset type 1
      diabetes, and 390 with type 2 diabetes. Serum concentrations of adiponectin,
      soluble tumor necrosis factor-alpha receptor 2 (sTNFRII), interleukin-6, hs-CRP,
      and total leukocyte number were measured. To evaluate the differences of these
      markers among diabetes types, we performed logistic regression models and
      evaluated area under the receiver-operating characteristic curve (AUCROC) values.
      RESULTS: The profile of innate immunity-related inflammatory markers correlated
      with metabolic syndrome components. LADA versus classic adult-onset type 1
      diabetes was independently related to sTNFRII (odds ratio [OR] 1.9 [95% CI 1.01
      3.97]; P = 0.047) and hs-CRP levels (OR 0.78 [95% CI 0.62-0.96]; P = 0.019), and
      a higher number of total leukocytes lowered the risk of LADA compared with type 2
      diabetes (OR 0.98 [95% CI 0.97-0.99]; P = 0.036). The logistic regression model
      including explanatory biomarkers explained 35% of the variation for LADA versus
      classic adult-onset type 1 diabetes (AUCROC 0.83 [95% CI 0.74-0.92]; P < 0.001)
      and 15% of the variation for LADA versus type 2 diabetes (AUCROC 0.73 [95% CI
      0.70-0.80]; P < 0.001). CONCLUSIONS: Inflammatory, adiposity, and immune-related
      markers could help to differentiate a LADA diagnosis from that of classic adult
      onset type 1 diabetes, and also LADA from that of type 2 diabetes, along with
      islet autoantibody positivity.

PMID- 29358495
TI  - History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to
      Genome Editing Technology.
AB  - Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are
      well-known acquired immunity systems that are widespread in archaea and bacteria.
      The RNA-guided nucleases from CRISPR-Cas systems are currently regarded as the
      most reliable tools for genome editing and engineering. The first hint of their
      existence came in 1987, when an unusual repetitive DNA sequence, which
      subsequently was defined as a CRISPR, was discovered in the Escherichia coli
      genome during an analysis of genes involved in phosphate metabolism. Similar
      sequence patterns were then reported in a range of other bacteria as well as in
      halophilic archaea, suggesting an important role for such evolutionarily
      conserved clusters of repeated sequences. A critical step toward functional
      characterization of the CRISPR-Cas systems was the recognition of a link between
      CRISPRs and the associated Cas proteins, which were initially hypothesized to be
      involved in DNA repair in hyperthermophilic archaea. Comparative genomics,
      structural biology, and advanced biochemistry could then work hand in hand, not
      only culminating in the explosion of genome editing tools based on CRISPR-Cas9
      and other class II CRISPR-Cas systems but also providing insights into the origin
      and evolution of this system from mobile genetic elements denoted casposons. To
      celebrate the 30th anniversary of the discovery of CRISPR, this minireview
      briefly discusses the fascinating history of CRISPR-Cas systems, from the
      original observation of an enigmatic sequence in E. coli to genome editing in
      humans.

PMID- 29358496
TI  - Partially Reciprocal Replacement of FlrA and FlrC in Regulation of Shewanella
      oneidensis Flagellar Biosynthesis.
AB  - In some bacteria with a polar flagellum, an established regulatory hierarchy
      controlling stepwise assembly of the organelle consists of four regulators: FlrA,
      sigma54, FlrBC, and sigma28 Because all of these regulators mediate the
      expression of multiple targets, they are essential to the assembly of a
      functional flagellum and therefore to motility. However, this is not the case for
      the gammaproteobacterium Shewanella oneidensis: cells lacking FlrB, FlrC, or both
      remain flagellated and motile. In this study, we unravel the underlying
      mechanism, showing that FlrA and FlrC are partially substitutable for each other
      in regulating flagellar assembly. While both regulators are bacterial enhancer
      binding proteins (bEBPs) for sigma54, FlrA differs from FlrC in its independence
      of sigma54 for its own transcription and its inability to activate the flagellin
      gene flaA These differences largely account for the distinct phenotypes resulting
      from the loss or overproduction of FlrA and FlrC.IMPORTANCE The assembly of a
      polar flagellum in bacteria has been characterized as relying on four regulators,
      FlrA, sigma54, FlrBC, and sigma28, in a hierarchical manner. They all are
      essential to the process and therefore to motility, except in S. oneidensis, in
      which FlrB, FlrC, or both together are not essential. Here we show that FlrA and
      FlrC, as bEBPs, are partially reciprocal in functionality in this species. As a
      consequence, the presence of one allows flagellar assembly and motility in the
      other's absence. Despite this, there are significant differences in the
      physiological roles played by these two regulators: FlrA is the master regulator
      of flagellar assembly, whereas FlrC fine-tunes motility. These intriguing
      observations open up a new avenue to further exploration of the regulation of
      flagellar assembly.

PMID- 29358497
TI  - OxyR-Dependent Transcription Response of Sinorhizobium meliloti to Oxidative
      Stress.
AB  - Reactive oxygen species such as peroxides play an important role in plant
      development, cell wall maturation, and defense responses. During nodulation with
      the host plant Medicago sativa, Sinorhizobium meliloti cells are exposed to H2O2
      in infection threads and developing nodules (R. Santos, D. Herouart, S. Sigaud,
      D. Touati, and A. Puppo, Mol Plant Microbe Interact 14:86-89, 2001,
      https://doi.org/10.1094/MPMI.2001.14.1.86). S. meliloti cells likely also
      experience oxidative stress, from both internal and external sources, during life
      in the soil. Here, we present microarray transcription data for S. meliloti wild
      type cells compared to a mutant deficient in the key oxidative regulatory protein
      OxyR, each in response to H2O2 treatment. Several alternative sigma factor genes
      are upregulated in the response to H2O2; the stress sigma gene rpoE2 shows OxyR
      dependent induction by H2O2, while rpoH1 expression is induced by H2O2
      irrespective of the oxyR genotype. The activity of the RpoE2 sigma factor in turn
      causes increased expression of two more sigma factor genes, rpoE5 and rpoH2
      Strains with deletions of rpoH1 showed improved survival in H2O2 as well as
      increased levels of oxyR and total catalase expression. These results imply that
      DeltarpoH1 strains are primed to deal with oxidative stress. This work presents a
      global view of S. meliloti gene expression changes, and of regulation of those
      changes, in response to H2O2IMPORTANCE Like all aerobic organisms, the symbiotic
      nitrogen-fixing bacterium Sinorhizobium meliloti experiences oxidative stress
      throughout its complex life cycle. This report describes the global
      transcriptional changes that S. meliloti makes in response to H2O2 and the roles
      of the OxyR transcriptional regulator and the RpoH1 sigma factor in regulating
      those changes. By understanding the complex regulatory response of S. meliloti to
      oxidative stress, we may further understand the role that reactive oxygen species
      play as both stressors and potential signals during symbiosis.

PMID- 29358498
TI  - Signal Peptidase Is Necessary and Sufficient for Site 1 Cleavage of RsiV in
      Bacillus subtilis in Response to Lysozyme.
AB  - Extracytoplasmic function (ECF) sigma factors are a diverse family of alternative
      sigma factors that allow bacteria to sense and respond to changes in the
      environment. sigmaV is an ECF sigma factor found primarily in low-GC Gram
      positive bacteria and is required for lysozyme resistance in several
      opportunistic pathogens. In the absence of lysozyme, sigmaV is inhibited by the
      anti-sigma factor RsiV. In response to lysozyme, RsiV is degraded via the process
      of regulated intramembrane proteolysis (RIP). RIP is initiated by cleavage of
      RsiV at site 1, which allows the intramembrane protease RasP to cleave RsiV
      within the transmembrane domain at site 2 and leads to activation of sigmaV
      Previous work suggested that RsiV is cleaved by signal peptidase at site 1. Here
      we demonstrate in vitro that signal peptidase is sufficient for cleavage of RsiV
      only in the presence of lysozyme and provide evidence that multiple Bacillus
      subtilis signal peptidases can cleave RsiV in vitro This cleavage is dependent
      upon the concentration of lysozyme, consistent with previous work that showed
      that binding to RsiV was required for sigmaV activation. We also show that signal
      peptidase activity is required for site 1 cleavage of RsiV in vivo Thus, we
      demonstrate that signal peptidase is the site 1 protease for RsiV.IMPORTANCE
      Extracytoplasmic function (ECF) sigma factors are a diverse family of alternative
      sigma factors that respond to extracellular signals. The ECF sigma factor sigmaV
      is present in many low-GC Gram-positive bacteria and induces resistance to
      lysozyme, a component of the innate immune system. The anti-sigma factor RsiV
      inhibits sigmaV activity in the absence of lysozyme. Lysozyme binds RsiV, which
      initiates a proteolytic cascade leading to destruction of RsiV and activation of
      sigmaV This proteolytic cascade is initiated by signal peptidase, a component of
      the general secretory system. We show that signal peptidase is necessary and
      sufficient for cleavage of RsiV at site 1 in the presence of lysozyme. This
      report describes a role for signal peptidase in controlling gene expression.

PMID- 29358499
TI  - Peptide Transporter CstA Imports Pyruvate in Escherichia coli K-12.
AB  - Pyruvate is an important intermediate of central carbon metabolism and connects a
      variety of metabolic pathways in Escherichia coli Although the intracellular
      pyruvate concentration is dynamically altered and tightly balanced during cell
      growth, the pyruvate transport system remains unclear. Here, we identified a
      pyruvate transporter in E. coli using high-throughput transposon sequencing. The
      transposon mutant library (a total of 5 * 105 mutants) was serially grown with a
      toxic pyruvate analog (3-fluoropyruvate [3FP]) to enrich for transposon mutants
      lacking pyruvate transport function. A total of 52 candidates were selected on
      the basis of a stringent enrichment level of transposon insertion frequency in
      response to 3FP treatment. Subsequently, their pyruvate transporter function was
      examined by conventional functional assays, such as those measuring growth
      inhibition by the toxic pyruvate analog and pyruvate uptake activity. The
      pyruvate transporter system comprises CstA and YbdD, which are known as a peptide
      transporter and a conserved protein, respectively, whose functions are associated
      with carbon starvation conditions. In addition to the presence of more than one
      endogenous pyruvate importer, it has been suggested that the E. coli genome
      encodes constitutive and inducible pyruvate transporters. Our results
      demonstrated that CstA and YbdD comprise the constitutive pyruvate transporter
      system in E. coli, which is consistent with the tentative genomic locus
      previously suggested and the functional relationship with the extracellular
      pyruvate sensing system. The identification of this pyruvate transporter system
      provides valuable genetic information for understanding the complex process of
      pyruvate metabolism in E. coliIMPORTANCE Pyruvate is an important metabolite as a
      central node in bacterial metabolism, and its intracellular levels are tightly
      regulated to maintain its functional roles in highly interconnected metabolic
      pathways. However, an understanding of the mechanism of how bacterial cells
      excrete and transport pyruvate remains elusive. Using high-throughput transposon
      sequencing followed by pyruvate uptake activity testing of the selected candidate
      genes, we found that a pyruvate transporter system comprising CstA and YbdD,
      currently annotated as a peptide transporter and a conserved protein,
      respectively, constitutively transports pyruvate. The identification of the
      physiological role of the pyruvate transporter system provides valuable genetic
      information for understanding the complex pyruvate metabolism in Escherichia
      coli.

PMID- 29358500
TI  - Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced
      Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE
      029 Study.
AB  - Purpose: Pembrolizumab monotherapy, ipilimumab monotherapy, and pegylated
      interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal
      cell carcinoma (RCC). We explored the safety and preliminary antitumor activity
      of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with
      advanced melanoma or RCC.Experimental Design: The phase Ib KEYNOTE-029 study
      (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced
      dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg
      every 3 weeks (Q3W) plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if <=6
      of 18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate
      for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients
      per dose level. Response was assessed per RECIST v1.1 by central review.Results:
      The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six
      patients experienced >=1 DLT. Grade 3 to 4 treatment-related adverse events
      occurred in 13 (59%) patients. Responses occurred in 5 of 12 (42%) patients with
      melanoma and 3 of 10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs
      occurred in 2 of 14 (14%) patients treated at dose level 1 (PEG-IFN 1
      MUg/kg/week) and 2 of 3 (67%) patients treated at dose level 2 (PEG-IFN 2
      MUg/kg/week). Grade 3 to 4 treatment-related adverse events occurred in 10 of 17
      (59%) patients. Responses occurred in 1 of 5 (20%) patients with melanoma and 2
      of 12 (17%) patients with RCC.Conclusions: Pembrolizumab 2 mg/kg Q3W plus
      ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in
      patients with advanced melanoma or RCC. The maximum tolerated dose of
      pembrolizumab plus PEG-IFN had limited antitumor activity in this population.
      Clin Cancer Res; 24(8); 1805-15. (c)2018 AACR.

PMID- 29358501
TI  - Glycogen Phosphorylase: A Novel Biomarker in Doxorubicin-Induced Cardiac Injury.
AB  - Extracellular vesicles containing glycogen phosphorylase, brain/heart (PYGB) have
      been demonstrated as a sensitive biomarker for normal cardiac injuries for
      patients after chemotherapy. Oxidative stress was suggested to be the mechanism
      behind the chemotherapy-induced tissue damage and augmented with mitochondrial
      antioxidant could be an effective means of early intervention. Clin Cancer Res;
      24(7); 1516-7. (c)2018 AACRSee related article by Yarana et al., p. 1644.

PMID- 29358502
TI  - Safety, Activity, and Biomarkers of SHR-1210, an Anti-PD-1 Antibody, for Patients
      with Advanced Esophageal Carcinoma.
AB  - Purpose: The current management of advanced esophageal squamous cell carcinoma
      (ESCC) remains unsatisfactory. We investigated the safety, efficacy, and
      biomarkers of SHR-1210, an anti-PD-1 antibody, in patients with recurrent or
      metastatic ESCC.Experimental Design: This study was part of a phase I trial in
      China. Patients with advanced ESCC who were refractory or intolerant to previous
      chemotherapy were enrolled. Eligible patients received intravenous SHR-1210 at a
      dose of 60 mg, with escalation to 200 and 400 mg (4-week interval after first
      dose followed by a 2-week schedule) until disease progression or intolerable
      toxicity. The associations between candidate biomarkers (PD-L1 and somatic
      mutation load) and the efficacy of SHR-1210 were also explored.Results: Between
      May 11, 2016, and December 9, 2016, a total of 30 patients from one site in China
      were enrolled. Ten patients (33.3%) had an independently assessed objective
      response. Median progression-free survival was 3.6 months (95% CI, 0-7.2). Three
      (10.0%) treatment-related grade 3 adverse events were reported: two (6.7%)
      pneumonitis and one (3.3%) increased cardiac troponin I. No grade 4 or grade 5
      treatment-related adverse events were reported. The exome sequencing and analysis
      showed that the mutational burden and the potential mutation-associated
      neoantigen count were associated with better responses. An objective response was
      more common in patients with PD-L1-positive tumors as defined by >=5% staining (7
      of 15 patients) than in those with PD-L1-negative tumors (1 of 9
      patients).Conclusions: In this population of ESCC patients, SHR-1210 had a
      manageable safety profile and promising antitumor activity. Clin Cancer Res;
      24(6); 1296-304. (c)2018 AACR.

PMID- 29358503
TI  - Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in
      Stage III Lung Cancer.
AB  - Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of
      care therapy for patients with stage III unresectable non-small cell lung cancer
      (NSCLC). Although cCRT is potentially curative, 5-year overall survival has
      hovered around 20%, despite extensive efforts to improve outcomes with increasing
      doses of conformal radiation and intensification of systemic therapy with either
      induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors
      have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In
      addition, preclinical and early clinical evidence suggests that chemotherapy and
      radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote
      antitumor immunity, which has led to the initiation of clinical trials testing
      these drugs in patients with stage III NSCLC. A preliminary report of a
      randomized phase III trial, the PACIFIC trial, demonstrated an impressive
      increase in median progression-free survival with consolidative durvalumab, a PD
      L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical
      and translational implications of integrating PD-1/PD-L1 inhibitors in the
      management of patients with unresectable stage III NSCLC. Clin Cancer Res; 24(6);
      1271-6. (c)2018 AACR.

PMID- 29358504
TI  - Further Investigation of the Role of ACYP2 and WFS1 Pharmacogenomic Variants in
      the Development of Cisplatin-Induced Ototoxicity in Testicular Cancer Patients.
AB  - Purpose: Adverse drug reactions such as ototoxicity, which occurs in
      approximately one-fifth of adult patients who receive cisplatin treatment, can
      incur large socioeconomic burdens on patients with testicular cancer who develop
      this cancer during early adulthood. Recent genome-wide association studies have
      identified genetic variants in ACYP2 and WFS1 that are associated with cisplatin
      induced ototoxicity. We sought to explore the role of these genetic
      susceptibility factors to cisplatin-induced ototoxicity in patients with
      testicular cancer.Experimental Design: Extensive clinical and demographic data
      were collected for 229 patients with testicular cancer treated with cisplatin.
      Patients were genotyped for two variants, ACYP2 rs1872328 and WFS1 rs62283056,
      that have previously been associated with hearing loss in cisplatin-treated
      patients. Analyses were performed to investigate the association of these
      variants with ototoxicity in this cohort of adult patients with testicular
      cancer.Results: Pharmacogenomic analyses revealed that ACYP2 rs1872328 was
      significantly associated with cisplatin-induced ototoxicity [P = 2.83 * 10-3, OR
      (95% CI):14.7 (2.6-84.2)]. WFS1 rs62283056 was not significantly associated with
      ototoxicity caused by cisplatin (P = 0.39); however, this variant was associated
      with hearing loss attributable to any cause [P = 5.67 * 10-3, OR (95% CI): 3.2
      (1.4-7.7)].Conclusions: This study has provided the first evidence for the role
      of ACYP2 rs1872328 in cisplatin-induced ototoxicity in patients with testicular
      cancer. These results support the use of this information to guide the
      development of strategies to prevent cisplatin-induced ototoxicity across
      cancers. Further, this study has highlighted the importance of phenotypic
      differences in replication studies and has provided further evidence for the role
      of WFS1 rs62283056 in susceptibility to hearing loss, which may be worsened by
      cisplatin treatment. Clin Cancer Res; 24(8); 1866-71. (c)2018 AACR.

PMID- 29358505
TI  - BMA backs GPs who wish to take legal action against Capita.

PMID- 29358506
TI  - Blockade of histone deacetylase 6 protects against cisplatin-induced acute kidney
      injury.
AB  - Histone deacetylase 6 (HDAC6) has been shown to be involved in various
      pathological conditions, including cancer, neurodegenerative disorders and
      inflammatory diseases. Nonetheless, its specific role in drug-induced
      nephrotoxicity is poorly understood. Cisplatin (dichlorodiamino platinum) belongs
      to an inorganic platinum - fundamental chemotherapeutic drug utilized in the
      therapy of various solid malignant tumors. However, the use of cisplatin is
      extremely limited by obvious side effects, for instance bone marrow suppression
      and nephrotoxicity. In the present study, we utilized a murine model of cisplatin
      induced acute kidney injury (AKI) and a highly selective inhibitor of HDAC6,
      tubastatin A (TA), to assess the role of HDAC6 in nephrotoxicity and its
      associated mechanisms. Cisplatin-induced AKI was accompanied by increased
      expression and activation of HDAC6; blocking HDAC6 with TA lessened renal
      dysfunction, attenuated renal pathological changes, reduced expression of
      neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, and
      decreased tubular cell apoptosis. In cultured human epithelial cells, TA or HDAC6
      siRNA treatment also inhibited cisplatin-induced apoptosis. Mechanistic studies
      demonstrated that cisplatin treatment induced phosphorylation of AKT and loss of
      E-cadherin in the nephrotoxic kidney, and administration of TA enhanced AKT
      phosphorylation and preserved E-cadherin expression. HDAC6 inhibition also
      potentiated autophagy as evidenced by increased expression of autophagy-related
      gene (Atg) 7 (Atg7), Beclin-1, and decreased renal oxidative stress as
      demonstrated by up-regulation of superoxide dismutase (SOD) activity and down
      regulation of malondialdehyde levels. Moreover, TA was effective in inhibiting
      nuclear factor-kappa B (NF-kappaB) phosphorylation and suppressing the expression
      of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6).
      Collectively, these data provide strong evidence that HDAC6 inhibition is
      protective against cisplatin-induced AKI and suggest that HDAC6 may be a
      potential therapeutic target for AKI treatment.

PMID- 29358507
TI  - Gene delivery of medium chain acyl-coenzyme A dehydrogenase induces physiological
      cardiac hypertrophy and protects against pathological remodelling.
AB  - We previously showed that medium chain acyl-coenzyme A dehydrogenase (MCAD, key
      regulator of fatty acid oxidation) is positively modulated in the heart by the
      cardioprotective kinase, phosphoinositide 3-kinase (PI3K(p110alpha)).
      Disturbances in cardiac metabolism are a feature of heart failure (HF) patients
      and targeting metabolic defects is considered a potential therapeutic approach.
      The specific role of MCAD in the adult heart is unknown. To examine the role of
      MCAD in the heart and to assess the therapeutic potential of increasing MCAD in
      the failing heart, we developed a gene therapy tool using recombinant adeno
      associated viral vectors (rAAV) encoding MCAD. We hypothesised that increasing
      MCAD expression may recapitulate the cardioprotective properties of
      PI3K(p110alpha). rAAV6:MCAD or rAAV6:control was delivered to healthy adult mice
      and to mice with pre-existing pathological hypertrophy and cardiac dysfunction
      due to transverse aortic constriction (TAC). In healthy mice, rAAV6:MCAD induced
      physiological hypertrophy (increase in heart size, normal systolic function and
      increased capillary density). In response to TAC (~15 weeks), heart weight/tibia
      length increased by ~60% in control mice and ~45% in rAAV6:MCAD mice compared
      with sham. This was associated with an increase in cardiomyocyte cross-sectional
      area in both TAC groups which was similar. However, hypertrophy in TAC rAAV6:MCAD
      mice was associated with less fibrosis, a trend for increased capillary density
      and a more favourable molecular profile compared with TAC rAAV6:control mice. In
      summary, MCAD induced physiological cardiac hypertrophy in healthy adult mice and
      attenuated features of pathological remodelling in a cardiac disease model.

PMID- 29358508
TI  - The Expanding World of N-MYC-Driven Tumors.
AB  - Enhanced and deregulated expression of N-MYC, a member of the MYC family of
      transcription factors, drives the development of multiple tumors, including
      tumors of the nervous and hematologic systems and neuroendocrine tumors in other
      organs. This review summarizes the cell-of-origin, biological features,
      associated signaling pathways, and current treatment strategies for N-MYC-driven
      tumors. We also highlight biological differences within specific tumor types that
      are driven by the different MYC proteins.Significance: N-MYC is a driver of
      multiple tumor types that are derived through a mechanism that involves direct
      differentiation within the same lineage (e.g., in the case of neuroblastoma,
      medulloblastoma, and acute myeloid leukemia) and is often associated with a poor
      prognosis. Emerging data suggest that N-MYC also drives other tumor types through
      a mechanism that promotes a lineage switch and that this switch may be exploited
      for therapeutic purposes. Cancer Discov; 8(2); 150-63. (c)2018 AACR.

PMID- 29358510
TI  - Ophthalmic artery MRI in an arteritis-related central retinal artery occlusion.

PMID- 29358511
TI  - Clinical Reasoning: A 60-year-old man with arm weakness and numbness.

PMID- 29358509
TI  - Neurotoxic chemicals in adipose tissue: A role in puzzling findings on obesity
      and dementia.
AB  - Midlife obesity is associated with increased risk of dementia, whereas late-life
      obesity is commonly associated with a lower risk of dementia. Although
      methodologic issues are often discussed in this apparent risk reversal, chronic
      exposure to low-dose organochlorine pesticides (OCPs), an emerging risk factor
      for dementia in general populations, may contribute to a direct explanation for
      these differences. OCPs are strong lipophilic chemicals with very long half-lives
      (several years), primarily stored in adipose tissue and very slowly released and
      metabolized over years. As serum concentrations of neurotoxic OCPs strongly
      correlate with brain OCPs (r = 0.95), any condition enhancing the release of OCPs
      from the adipose tissue into circulation would increase the risk of dementia.
      Increased release of OCPs from adipose tissue typically occurs in (1)
      dysfunctional adipocytes accompanied by uncontrolled lipolysis and (2) weight
      loss. Weight gain may help sequester circulating OCPs in adipose tissue. As
      obesity is the most common reason that adipocytes become dysfunctional, midlife
      obesity can increase dementia risk through the chronic release of OCPs into
      circulation. However, late-life obesity potentially decreases dementia risk
      because weight loss after midlife will increase the release of OCPs while weight
      gain may actually decrease the release. These countervailing forces may underlie
      paradoxical associations with dementia of obesity in midlife vs late life which
      is influenced by weight change after midlife. This hypothesis should be tested in
      future experimental and human studies on obesity and dementia.

PMID- 29358512
TI  - Editors' note: Blood pressure reduction and noncontrast CT markers of
      intracerebral hemorrhage expansion.

PMID- 29358513
TI  - Reader response: Blood pressure reduction and noncontrast CT markers of
      intracerebral hemorrhage expansion.

PMID- 29358514
TI  - Author response: Blood pressure reduction and noncontrast CT markers of
      intracerebral hemorrhage expansion.

PMID- 29358515
TI  - Editors' note: Effects of increasing IV tPA-treated stroke mimic rates at CT
      based centers on clinical outcomes.

PMID- 29358516
TI  - Reader response: Effects of increasing IV tPA-treated stroke mimic rates at CT
      based centers on clinical outcomes.

PMID- 29358517
TI  - Author response: Effects of increasing IV tPA-treated stroke mimic rates at CT
      based centers on clinical outcomes.

PMID- 29358518
TI  - Assessing structure and function of myelin in cervical spondylotic myelopathy:
      Evidence of demyelination.

PMID- 29358519
TI  - Pearls & Oy-sters: Positional vertigo and vertical nystagmus in medulloblastoma:
      A picture is worth a thousand words.

PMID- 29358520
TI  - Teaching NeuroImages: Visual loss as a rare complication of mechanical
      thrombectomy.

PMID- 29358521
TI  - Teaching NeuroImages: A diffuse infiltrating retinoblastoma.

PMID- 29358523
TI  - Correction to: Enlightenment and Challenges Offered by DAWN Trial (DWI or CTP
      Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting
      Strokes Undergoing Neurointervention With Trevo).

PMID- 29358524
TI  - Vaginal microbiota composition and association with prevalent Chlamydia
      trachomatis infection: a cross-sectional study of young women attending a STI
      clinic in France.
AB  - OBJECTIVES: New molecular techniques have allowed describing groups of bacterial
      communities in the vagina (community state types (CST)) that could play an
      important role in Chlamydia trachomatis (CT) infection. Our aim was to describe
      the distribution of CST in a population of young women in France. METHODS: A
      cross-sectional study was carried out in June 2015 among anonymous young women
      attending a STI clinic in Bordeaux, France. Participants provided a vaginal
      sample for CT screening and sociodemographic data. CT was diagnosed using the
      Aptima-combo 2 transcription-mediated-amplification assay. Vaginal microbiota
      composition was characterised using 16S rRNA gene amplicon sequencing. RESULTS:
      Microbiota composition and CT status were available for 132 women. CST dominated
      by Lactobacillus crispatus (CST-I), L. iners (CST-III) and a diversity of
      anaerobes (CST-IV) represented 37.1%, 38.6% and 22.0% of the sample,
      respectively. Twenty-one out of 132 women were CT positive. Proportions of CT
      positive women were higher for samples belonging to CST-III (21.6%) and CST-IV
      (17.2%) than to CST-I (8.2%). CONCLUSIONS: Five CST were found in 132 young women
      from a STI clinic in France. These CSTs were not significantly associated with CT
      but higher proportions of CT-positive women were found in CST-III and CST-IV,
      consistent with a previous study in the Netherlands. Though our study lacked
      statistical power and was cross-sectional, it is a necessary first step to
      understand the structure of the vaginal microbiota in French women with or
      without infection before performing in-depth longitudinal studies.

PMID- 29358525
TI  - Risk factors for oropharyngeal gonorrhoea in men who have sex with men: an age
      matched case-control study.
AB  - OBJECTIVES: Oropharyngeal gonorrhoea is common among men who have sex with men
      (MSM). We aimed to clarify which oral sex practices were independent risk factors
      for oropharyngeal gonorrhoea: tongue kissing, receptive oro-penile sex (fellatio)
      or insertive oro-anal sex (rimming), and whether daily use of mouthwash and
      recent antibiotic use was protective. METHODS: In 2015, we conducted an age
      matched case-control study of MSM who attended the Melbourne Sexual Health
      Centre. Cases had tested positive for oropharyngeal gonorrhoea by nucleic acid
      amplification testing, and controls had tested negative. Questionnaire items
      included tongue kissing, oral sex practices, condom use, recent antibiotic use,
      mouthwash use and alcohol consumption. RESULTS: We identified 177 cases, age
      matched to 354 controls. In univariable analyses, cases were 1.90 times (95% CI
      1.13 to 3.20) more likely than controls to have had casual sexual partners (CSP)
      in the preceding 3 months, were 2.17 times (95% CI 1.31 to 3.59) more likely to
      have kissed CSP and were 2.04 times (95% CI 1.26 to 3.30) more likely to have had
      receptive oro-penile sex with CSP. Oropharyngeal gonorrhoea was not associated
      with insertive oro-anal sex or mouthwash use. The number of CSP for tongue
      kissing and receptive oral sex and total CSP were highly correlated, and in
      multivariable analysis neither kissing nor receptive oro-penile sex was
      significantly associated with having oropharyngeal gonorrhoea, after adjusting
      for total number of CSP. CONCLUSIONS: The finding that oropharyngeal gonorrhoea
      was associated with a higher number of sexual partners but not specific sexual
      practices highlights the need for further research in the area of gonorrhoea
      transmission to define the probability of transmission from specific sex acts.

PMID- 29358526
TI  - Modelling individual vulnerability to sexually transmitted infections to optimise
      intervention strategies: analysis of surveillance data from Kalamazoo County,
      Michigan, USA.
AB  - OBJECTIVE: We modelled individual vulnerability to STI using personal history of
      infection and neighbourhood characteristics. METHODS: Retrospective chlamydia and
      gonorrhoea data of reported confirmed cases from Kalamazoo County, Michigan for
      2012 through 2014 were analysed. Unique IDs were generated from the surveillance
      data in collaboration with local health officials to track the individual STI
      histories. We then examine the concept that individuals with similar STI
      histories form a 'peer' group. These peer group include: (1) individuals with a
      single chlamydia; (2) individuals with single gonorrhoea; (3) individuals with
      repeated cases of one type of STI and (4) individuals that were diagnosed with
      both infections during the study period. Using Kernel density estimation, we
      generated densities for each peer group and assigned the intensity of the
      infection to the location of the individual. Finally, the individual
      vulnerability was characterised through ordinary least square regression (OLS)
      using demographics and socioeconomic variables. RESULTS: In an OLS regression
      adjusted for frequency of infection, individual vulnerability to STI was only
      consistently significant for race and neighbourhood-level socioeconomic status
      (SES) in all the models under consideration. In addition, we identified six areas
      in three townships in Kalamazoo County that could be considered for unique
      interventions based on overlap patterns among peer groups. CONCLUSIONS: The
      results provide evidence that individual vulnerability to STI has some dependency
      on individual contextual (race) and exogenous factors at the neighbourhood level
      such as SES, regardless of that individual's personal history of infection. We
      suggest place-based intervention strategies be adopted for planning STI
      interventions instead of current universal screening of at-risk populations.

PMID- 29358527
TI  - Three-dimensional Printing in Reconstructive Oral and Maxillofacial Surgery.
AB  - Three-dimensional (3D) printing involves the process of constructing a 3D solid
      object from a digital file. Charles Hull was the first to introduce 3D printer in
      1983 by using the technique of stereolithography.1 Since the 1990s 3D printing
      has gained attention in the field of medicine where more precision is required
      and has largely replaced the traditional technique in prosthetic works.2,3.

PMID- 29358528
TI  - Effect of the Curing Temperature of Dental Composites evaluated with a
      Fluorescent Dye.
AB  - AIM: With the development of the light-emitting diode (LED) to photo-activate
      composite resin, greater intensities could be reached without greater elevation
      of temperature in the mass of the composite resin and in the dental structure
      arisen from the irradiance in comparison to halogen equipments. This new scenario
      created a necessity to investigate the influence of temperature over the
      composite polymerization. MATERIALS AND METHODS: Several curing temperatures
      (Tcure- 0, 25, 50, 75, and 100 degrees C) were used to polymerize a composite
      resin (Filtek Z250, 3M ESPE) for 40 and 60 s, using the halogen equipment Gnatus
      Optilight Digital (halogen) and two LEDs that use a new technology to assembly
      the diodes: LEC 1000 and bright LEC (MM Optics) (LED 1 and LED 2 respectively).
      The influence of curing temperature, added by the other variables studied, was
      evaluated using a methodology developed and improved at IFSC/USP, in which the
      penetration of a fluorescent dye in the body of the photopolymerized composite
      resin was quantified using fluorescence spectroscopy. RESULTS: According to the
      final data submitted to an analysis of variance, the presence of two groups of
      results could be verified: Between 0 and 25 degrees C, both had a great
      percentage of the dye penetration compared with other Tcure with a variation in
      penetration from 69.26 +/- 8.19% to 90.99 +/- 3.38%. In this analysis, the
      effects of time and temperature were highly notable (p < 0.05) and the lesser
      value of dye penetration took place at 60 s of photoactivation This penetration
      was, in average, smaller with the Tcure of 25 degrees C. The results showed that
      there was an interaction between the equipment and time and between time and
      temperature; the other group is regarding the Tcure was from 50, 75, and 100
      degrees C, despite the p = 0.05, the effect of temperature was notable. The
      penetration of the dye ranged from 8.87 +/- 3.55 to 39.47 +/- 8.9%. The effects
      of equipment and time were highly notable. The penetration with the time of 60 s
      was in average smaller. Except with the equipment LED 1, the percentages of the
      dye penetration were greater with the Tcure of 100 degrees C. The smallest
      average was the Tcure of 50 degrees C and 60 s of photoactivation. CONCLUSION:
      Based on the available data regarding the influence of curing temperature on the
      polymerization process of composite resins, was possible to concluded that small
      increments of heat increased the degree of conversion. We can assume that the
      energy supply through the generation of heat by the photopolymerizing devices can
      function as a heating medium for the reagent system by reducing its viscosity and
      increasing the mobility and agitation of its components. CLINICAL SIGNIFICANCE:
      The dentist must be aware of the effects that exist between the activation
      devices on the light output and their heat transmission to the composite and the
      tooth itself. This heat transmission might create a polymer with better
      characteristics.

PMID- 29358529
TI  - Diametral Tensile Strength, Flexural Strength, and Surface Microhardness of
      Bioactive Bulk Fill Restorative.
AB  - AIM: The aim was to perform comparative analysis of bioactive, contemporary bulk
      fill resin-based composites (RBCs) and conventional glass-ionomer materials for
      flexural strength (FS), diametral tensile strength (DTS), and Vickers hardness
      number (VHN) in the presence of thermocycling. MATERIALS AND METHODS: Five
      restorative materials [Tetric N-Ceram Bulk Fill; smart dentin replacement (SDR)
      Flowable Material; Bioactive restorative material (ACTIVA Bulk Fill); Ketac
      Universal Aplicap; and GC Fuji II] were evaluated for DTS, FS, and VHN. Half the
      samples in each material group were ther-mocycled. The DTS was performed under
      compressive load at a cross-head speed of 1.0 mm/min. The FS was assessed by
      three-point bending test at a cross-head speed of 0.5 mm/min. The VHN was
      determined using a Vickers diamond indenter at 50 gf load for 15 seconds.
      Differences in FS, DTS, and VHN were analyzed using analysis of variance (ANOVA)
      and Tukey post hoc tests at a = 0.05 level of significance. RESULTS: N-Ceram,
      ACTIVA, and SDR demonstrated the highest and comparable (p > 0.05) FS. The SDR
      had the highest DTS value (141.28 +/- 0.94), followed by N-Ceram (136.61 +/-
      1.56) and ACTIVA (129.05 +/- 1.78). Ketac had the highest VHN value before and
      after thermocycling. CONCLUSION: ACTIVA showed mechanical properties (FS and DTS)
      comparable with bulk-fill resin composite materials. ACTIVA showed potential for
      durability, as VHN was comparable post-thermocycling. CLINICAL SIGNIFICANCE:
      Bioactive materials showed acceptable DTS and FS values. However, hardness was
      compromised compared with included materials. ACTIVA Bulk Fill shows potential
      for dentin replacement but it needs to be covered with a surface-resistant
      restorative material. Further studies to improve surface characteristics of
      ACTIVA Bulk Fill are recommended.

PMID- 29358530
TI  - Study Model-based Evaluation of Built-in Tip, Torque, and In-out Characteristics
      of a Third-generation Preadjusted Edgewise Appliance.
AB  - AIM: The aim of the study was to evaluate the clinical effectiveness of MBTTM
      preadjusted edgewise appliance (PEA) in terms of achieving the optimal expression
      of its built-in characteristics of tip, torque, and in-out. MATERIALS AND
      METHODS: Pretreatment and posttreatment study models of 20 subjects who received
      full fixed appliance treatment involving four first premolar extractions using
      the MBTTM appliance were measured for tip, torque, and in-out using the method
      described by Andrews. Treatment changes were analyzed statistically, and the
      posttreatment measurements were compared with the MBTTM specifications as well as
      Andrews' values for the above-mentioned parameters. RESULTS: Except for the
      maxillary canines and second premolars, the built-in tip of MBTTM appliance was
      nearly fully expressed, though there was some lack of correlation with Andrews'
      values. Despite the fact that the full amount of torque built into the MBTTM
      appliance was not expressed, torque measurements for all teeth except the
      maxillary second premolars and the first molars showed either no statistically
      significant difference or were significantly higher than Andrews' values for
      these teeth. In-out readings were lower than both MBTTM and Andrews' values, but
      the relative order of crown prominences was similar. Conclusion and clinical
      significance: The MBTTM appliance is thus effective in ensuring a successful
      treatment result, though individual adjustments may be necessary for optimal
      tooth positioning at the end of the treatment, as with any preadjusted appliance.

PMID- 29358531
TI  - Children's Menu Diversity: Influence on Fluoride Absorption and Excretion.
AB  - AIM: The aim of this study is to determine the influence of children's menu
      diversity on the absorption and excretion of fluoride. MATERIALS AND METHODS: The
      experimental, longitudinal, quantitative study was carried out in a city without
      fluoridation in water supply. A total of 16 adult volunteers (>63.9 kg)
      participated in the study who, after a 12-hour fast, ingested two types of
      children's meals, whose quantity and diversity were determined after weighing the
      meals best consumed by children at a kindergarten in Campinas, Sao Paulo: Simple
      child meal (SCM; n = 8) and hearty child meal (HCM; n = 8). The fluoride gel
      residual after professional application (12,300 ppm, 30.75 mg F, pH = 4.65) was
      simulated 15 minutes after feeding. Saliva samples (in time intervals of 0, 15,
      30, and 45 minutes and 1, 2, 3, 4, 6, and 12 hours after ingestion of the
      fluorine solution) and urine of the volunteers were analyzed at 24 hours.
      Fluoride concentrations were determined using a selective ion electrode. Data
      were analyzed by analysis of variance for repeated measurements (PROC
      MIXED)/Tukey-Kramer. RESULTS: The concentrations of fluoride in saliva at 0 and
      15 minutes and after 6 hours were the same between groups (p > 0.05). From 30
      minutes to 4 hours after ingestion, the SCM group showed a higher concentration
      of fluoride in the saliva, which has a higher absorption (p < 0.05). The fluoride
      concentration in the urine did not differ between groups at both collection times
      (p > 0.05), and for both, the fluoride concentration in the urine increased in
      the final measurement (p < 0.05). CONCLUSION: The children's menu diversity
      influenced the absorption of fluoride so that the topical application of fluoride
      should be performed in infants fed preferably after the fuller diet and following
      the established guidelines to ensure the safety of the procedure. CLINICAL
      SIGNIFICANCE: Knowledge of the influence of the children's menu diversity on
      fluoride metabolism after professional application is important so that the
      actions of fluoride therapy may be planned in a safer manner and be based on the
      reality of the universe of children.

PMID- 29358532
TI  - Effect of Dental Prophylaxis Techniques on the Surface Roughness of Resin
      Composites.
AB  - AIM: The aim of this study is to evaluate the effect of dental prophylaxis
      techniques on surface roughness of composite resins. MATERIALS AND METHODS: A
      total of 36 nanohybrid resin composite test specimens were fabricated and divided
      into three groups (n = 12). They were kept in distilled water at 37 degrees C for
      24 hours and submitted to the finishing and polishing technique. For the
      prophylactic techniques, in group G1, a mixture of pumice stone and distilled
      water was used with the aid of a rubber cup; in group G2, Herjos-F prophy paste
      was used with a rubber cup; and in group G3, a bicarbonate jet spray was used.
      Afterward, all the samples were repolished using the Soflex pop-on disks. A
      roughness meter was used to measure surface roughness at three points in time:
      Before the prophylactic techniques (1st evaluation), afterward (2nd evaluation),
      and following repeat polishing (3rd evaluation). RESULTS: It was found that
      roughness values changed significantly between the 1st and 2nd evaluations (p <
      0.05) and between the 2nd and 3rd evaluations (p < 0.05), showing that the change
      in roughness depended on the type of prophylactic treatment. Roughness was
      significantly higher after the bicarbonate jet (p < 0.05). CONCLUSION:
      Prophylaxis using the sodium bicarbonate jet significantly altered the roughness
      of nanoparticle-reinforced resin. CLINICAL SIGNIFICANCE: Dental prophylaxis is
      the most common practice employed to remove bacterial plaque and other coatings.
      However, one side effect of the cleaning may be a rougher surface subject to
      degradation and staining. The correct use of prophylactic devices and avoiding
      prolonged use on resin restorations reduce surface roughness.

PMID- 29358534
TI  - Effect of Topical Honey on Mandibular Bone Defect Healing in Rats.
AB  - AIM: In medicine, honey is known for its various biological or pharmacological
      effects, from wound dressing to anticancero-genic and from anti-inflammatory to
      antibacterial activities. The aim of the current study was to evaluate the effect
      of honey on healing of mandibular bone defects in a rat model. MATERIALS AND
      METHODS: This animal study was performed on 24 wild-type Wistar rats. Following
      shaving, disinfection, and extraoral incision, a 2 * 2 mm defect was created at
      mandibular angle. In the experimental group, the defect was filled with sterile
      honey, while it was left unfilled in the control group. The rats were sacrificed
      after 2 and 4 weeks and defects were assessed histologically. The results were
      compared using Mann-Whitney U-test (alpha = 0.05). RESULTS: After 2 weeks, five
      samples of the experimental group were in mineralization phase, while all samples
      of the control group were in the vascularization phase (p = 0.015). After 4
      weeks, the defects were filled in four samples of the experimental group, while
      all samples of the control group were in the mineralization stage (p = 0.002).
      Histomorphometric assessment revealed that the mean new bone formation in the
      experimental group was significantly more than the control group, both after 2
      and 4 weeks (p = 0.041). CONCLUSION: The results showed that honey could
      accentuate bone healing of mandibular small defects in rats. CLINICAL
      SIGNIFICANCE: Honey might have potential in repair of human alveolar bone
      defects.

PMID- 29358533
TI  - Prevalence of Periodontitis and Soft Tissue Lesions among Human Immunodeficiency
      Virus-positive Patients on Antiretroviral Therapy in Raichur Taluk, Karnataka,
      India.
AB  - INTRODUCTION: In countries where human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) is widespread and highly active
      antiretroviral therapy (HAART) medications are too expensive, or patients are
      failing HAART, oral disease management and risk remain an important issue. AIM:
      The aim of the study was to evaluate the prevalence of oral mucosal lesions and
      periodontitis among the HIV-positive adult patients and assess the association of
      these lesions with age, sex, duration of HIV, time on ART, dietary habits, and
      oral hygiene habits. MATERIALS AND METHODS: Sample size was 170. Demographic data
      of the patients along with community periodontal index (CPI) and loss of
      attachment (LA) were recorded. Oral soft tissue lesions, such as ulcerations,
      sores, erosions, and fissures were also recorded. The study was carried out in
      Raichur Taluk, Karnataka, India. Convenience sampling design was followed.
      Statistical Package for the Social Sciences (SPSS) version 20.0 (Chicago, USA)
      was used for data analysis. Chi-square test was carried out; p < 0.05 was
      considered to be statistically significant. RESULTS: There was no association
      between the oral mucosal conditions and the age and the adverse habits, such as
      tobacco and alcohol, CD4 count, and the time duration of HIV and ART among these
      patients. A higher percentage of people with 4 to 5 mm of pockets was seen with
      those who cleaned their teeth with a finger, which was statistically significant.
      CLINICAL SIGNIFICANCE: The present study highlights the poor condition of the
      oral health of these patients and their unmet dental needs.

PMID- 29358536
TI  - Pulp Stones, Prevalence and Distribution in an Iranian Population.
AB  - AIM: This study determined the prevalence and distribution of pulp stones in the
      permanent dentition of an adult population using their periapical radiographs.
      MATERIALS AND METHODS: The study followed a cross-sectional design. A total of
      800 periapical radiographs collected from 412 patients attending dental clinics
      in Kerman, Islamic Republic of Iran, were examined using magnification. RESULTS:
      Pulp stones were present in 9.6% of all permanent teeth examined, being most
      common in maxillary first and second molars, followed by mandibular first and
      second molars. They were present in 31.5% of all adult patients, with a
      significantly increased prevalence in females compared with males (40.5 vs 23.9%,
      chi-squared test p < 0.001). There was also an increased prevalence with age.
      CONCLUSION: Based on the results of this study, clinicians should expect to
      encounter pulp stones most commonly in the pulp chambers of maxillary first and
      second molars, particularly in older female patients. CLINICAL SIGNIFICANCE: Pulp
      stones depending on their size and location can pose challenges to endodontic
      treatment. They obstruct access to the canal orifices and thus complicate
      endodontic treatment. Knowing where and when pulp stones are likely to occur
      improves the quality of root canal treatments.

PMID- 29358535
TI  - Evaluation of Hybrid Layer and Bonding Interface after Water Storage with and
      without the Usage of 2% Chlorhexidine: A Scanning Electron Microscope Study.
AB  - AIM: Restorative dentists employ different bonding systems between the resin and
      the dentin and other dentinal tissues to achieve the goal of micromechanical
      retention. Studies have shown that the bond between composite and dentin degrades
      over time because of the action of matrix metalloproteinases (MMPs) on collagen
      fibrils left unprotected by acid etching. The MMPs may be partially responsible
      for hybrid layer degradation. Since chlorhexidine (CHX) inhibits MMPs, we
      hypothesized that CHX would decelerate the loss of resin-dentin bonds. Hence,
      this in vitro study is intended to evaluate the effects of 2% CHX on hybrid layer
      and bonding interface. MATERIALS AND METHODS: Totally, 40 freshly extracted
      molars were randomly divided into four experimental groups. In all 40 specimens,
      class II cavities were prepared to a depth of 1 mm below the dentinoenamel
      junction with no axial wall, but the elimination of the proximal enamel ridge.
      The teeth were then randomly divided into four experimental groups, i.e., All
      Bond 2 without 2% CHX (group I), All Bond 2 with 2% CHX (group II), One Coat 7.0
      without 2% CHX (group III), and One Coat 7.0 with 2% CHX (group IV). All the
      specimens were derooted and sectioned mesiodistally into two halves and placed
      under water at 37 degrees C for 3 months and observed under scanning electron
      microscope for the hybrid layer and resin tag formation. RESULTS: Groups I and II
      showed statistically significant difference when the presence/absence of resin
      tags was compared. When groups III and IV were compared for the presence/absence
      of hybrid layer and resin tags, the results were statistically significant.
      CONCLUSION: Between all the four experimental groups, irrespective of the bonding
      systems used, we concluded that groups with 2% CHX usage showed promising results
      with presence/ absence of hybrid layer and resin tags formation. CLINICAL
      SIGNIFICANCE: Studies suggest that the bond between composite and dentin degrades
      over time because of the action of MMPs on collagen fibrils left unprotected by
      acid etching. Measures should be taken to prevent this from happening and thus
      allow bond between composite and dentin last longer.

PMID- 29358537
TI  - Radiographic Evaluation of Post-core Restorations fabricated by Dental Students
      at Jazan University.
AB  - AIM: Post and core procedures are important clinical methods in routine dental
      practice. The present research aimed to radiographically assess the quality of
      post seating performed by undergraduate students at the College of Dentistry,
      Jazan University. MATERIALS AND METHODS: A total of 343 periapical X-rays of
      cemented posts (170 from males and 173 from females) were assessed. The
      assessment covered tooth type, arch, gender, type of post, length of post in
      relation to the crown and root lengths, the presence of any abnormality in post
      space, status of the remaining gutta-percha (GP), and the presence or absence of
      spaces between the end of post and GP. Data were analyzed using the Statistical
      Package for the Social Sciences (SPSS) program (version 21), and associations
      between variables were determined using chi-squared or Fisher's exact tests.
      RESULTS: Maxillary teeth were the most frequently restored with posts, and the
      majority (41%) comprised incisors. Similarly, glass fiber post (69%) and taper
      shaped posts (86%) were the most used posts. The majority of posts (81.6%)
      featured a width one-thirds that of the root. Lengths of posts were twice (58%)
      or equal to (51%) crown and root length respectively. More than 55% of cases
      presented 3 to 5 mm of GP at their apical portion, and 29% reached more than 5
      mm. Approximately 5 to 8% of assessed cases revealed widening of periodontal
      ligaments, presence of periapical pathologies, and deviation of posts from the
      canal wall. Most cases (75%) showed the absence of space between GP and the post
      end. CONCLUSION: Qualities of assessed post and core restorations conducted by
      the 6th year dental students were clinically acceptable. CLINICAL SIGNIFICANCE:
      Periodic evaluation to determine the quality of delivered treatments is a vital
      cue for health service authorities. This evaluation will improve quality of
      services and treatments provided by dental students to their patients under the
      supervision of the faculty. Results obtained will also provide authorities with a
      clear feedback about academic infrastructure.

PMID- 29358538
TI  - Assessment of Ions released from Three Types of Orthodontic Brackets immersed in
      Different Mouthwashes: An in vitro Study.
AB  - AIM: Herbs are used widely in medicine. The purpose of the present study was to
      assess the ion release from gold-plated orthodontic bracket compared with other
      stainless steel brackets, and based on the findings of the study, the
      orthodontists can choose the most biocompatible brackets and mouthwashes useful
      in the clinical practice. MATERIALS AND METHODS: A total of 150 orthodontic
      brackets from OrthotechnologyTM Company, USA (50 stainless steel one-piece
      brackets, 50 stainless steel two-piece brackets, and 50 gold brackets) were
      immersed in four mouthwashes in addition to distilled water. Ten of each type of
      brackets in every media were immersed under 37 degrees C for 45 days. Ions
      released in these mouthwashes were measured, and comparisons among different
      bracket types and among various mouthwashes were done by one-way analysis of
      variance (ANOVA) and then with Games-Howell tests. RESULTS: Increased amounts of
      ions released in herbal mouth-washes were recorded in gold and two-piece brackets
      in comparison with one-piece stainless steel brackets. CONCLUSION: Herbal
      mouthwashes must be used with caution as they showed an increased amount of ions
      released in comparison with chlorhexidine. One-piece stainless steel bracket
      system is the most compatible bracket type, as they released the least amount of
      ions. CLINICAL SIGNIFICANCE: One-piece stainless steel brackets are better than
      two-piece brackets in terms of ions released.

PMID- 29358540
TI  - Patients' Knowledge and Perceived Barriers toward Replacement of Missing Teeth
      among Respondents of Hail City, Kingdom of Saudi Arabia.
AB  - AIM: Teeth maintain the functionality and esthetic of oral cavity, they are also
      important for psychological and social well-being. This study aims to assess
      awareness of patients toward replacement of missing teeth. People with unrestored
      or missing teeth tend to have poor self-esteem and oral health-related quality of
      life; hence, their knowledge toward restoring and replacing teeth is an important
      aspect to be measured. MATERIALS AND METHODS: It was an observational study
      having a cross-sectional design. Face- and content-validated questionnaire was
      used as study tool. Nonprobability, convenient sampling technique was employed
      that yielded information from 183 respondents residing in various areas of Hail
      city. Data were collected after written informed consent. The study was approved
      by the University of Hail ethical committee. RESULTS: Two hundred questionnaires
      were distributed, out of which 183 were returned. Regarding knowledge of
      restoring missing teeth, 145 (79.2%) respondents know that function and esthetic
      can be maintained by replacing missing teeth. Information about the availability
      of various types of prosthesis was mostly obtained by them through their dentist
      (70; 48.3%), while books/magazines/Internet was the second source (38; 26.2%) and
      37 (25.5%) heard it from someone who has already undergone the replacement of
      teeth. CONCLUSION: The present study indicated that a good number of respondents
      have the knowledge of teeth replacement, and dentists were the most common source
      of information to the patients in terms of education about different treatment
      options. CLINICAL SIGNIFICANCE: Evaluate and plan treatment options based on
      patients' expectations and perceptions.

PMID- 29358539
TI  - Effectiveness of Antimicrobial Therapy after Extraction of Impacted Mandibular
      Third Molar: A Randomized Clinical Trial.
AB  - AIM: The present study was conducted with the aim of evaluating the effectiveness
      of antimicrobial therapy following extraction of an impacted mandibular third
      molar. MATERIALS AND METHODS: This randomized controlled trial was conducted on a
      total of 60 patients who were randomly assigned into three groups: Group I
      individuals were given 625 mg of combined amoxicillin and clavulanic acid tablet;
      625 mg of combined amoxicillin and clavulanic acid tablet + 400 mg metronidazole
      tablet was given to group II individuals; whereas group III individuals were
      assigned no treatment. All the individuals underwent surgical extraction of
      impacted mandibular third molars under strict aseptic techniques, with minimal
      trauma to the surrounding tissues. Mouth opening in millimeters was recorded
      postoperatively using Vernier calipers on the 1st, 3rd, 5th, and 7th days. A 4
      point visual analog scale (VAS) was used for assessing postoperative pain.
      Patient satisfaction was further assessed in a subjective manner using a graded
      scale from "very satisfied" to "very unsatisfied". RESULTS: The present study
      included individuals between the ages of 20 and 35 years. Group II individuals
      showed slightly better satisfaction than the other group individuals. There was
      no statistically significant difference between the mean age of groups. It was
      observed that on day 3, the number of individuals with severe pain was slightly
      reduced in the group I compared with group III individuals. On day 5,
      participants with no pain were significantly more in group II followed by group
      I. Furthermore, there was a statistically significant difference between the
      study groups with respect to mouth opening on days 3 and 5. CONCLUSION: It was
      concluded from this trial that the administration of postoperative antimicrobials
      showed no significant differences in the degree of postoperative complications
      that occur following the surgical extraction of impacted mandibular third molars.
      CLINICAL SIGNIFICANCE: Antimicrobial drugs are routinely used to reduce the
      chances of surgical site infection, either preopera-tively or postoperatively.
      Therefore, the clinicians should have sound knowledge about choosing the better
      antimicrobial drug after the extraction of impacted third molars.

PMID- 29358541
TI  - Long-term Retrospective Study based on Implant Success Rate in Patients with Risk
      Factor: 15-year Follow-up.
AB  - AIM: The purpose of this retrospective study is to assess implant success rates
      with various risk factors. MATERIALS AND METHODS: Two hundred patients with a
      total of 650 implants were selected. Risk factors, such as smoking,
      antidepressants, bruxism, diabetes, and bone augmentation procedures were
      considered, and patients were followed up for a period of 8 to 15 years. RESULTS:
      Of 650 implants placed, the success rate was 88%, i.e., a total of 572 implants
      were successful. A total of 78 implants were considered failure; and out of 78,
      twenty implants were surgically removed. CONCLUSION: Based on this study's
      results, it is concluded that risk factors, such as smoking, bruxism, diabetes,
      and bone augmentation play an important role in success rate of dental implants.
      CLINICAL SIGNIFICANCE: Several factors, such as bruxism, diabetes, and supporting
      bone can play an important role in dental implant success.

PMID- 29358542
TI  - Clinicomicrobiological Evaluation of 2% Chitosan Mouthwashes on Dental Plaque.
AB  - AIM: This study was conducted to evaluate microbiological and clinical effects of
      a chitosan chlorhexidine (CH) mouthrinse on plaque control. MATERIALS AND
      METHODS: Subjects were divided into three groups. Group I included 15 subjects
      who used 0.2% chlorhexidine digluconate (CHX), group II included 15 subjects who
      used 2% chitosan (CH) solution, and group III involves 15 subjects who used 0.2%
      chlorhexidine/2% CH combination. Plaque index (PI), gingival index (GI), and
      probing depth (PD) were recorded at the baseline, on day 0, and after 4 days.
      Supragingival plaque samples were subjected for microbiological evaluation.
      Statistical analysis was done using statistical software IBM Statistical Package
      for the Social Sciences (SPSS), version 21. RESULTS: Plaque index was lowest in
      group I at day 0, while it was highest in group III. At day 4, PI was highest in
      group II, while lowest in group III. Gingival index was lowest in group I and
      highest in group II at day 0, and lowest in group I and highest in group III at
      day 4. There was no statistical difference in Streptococcus mutans (S. mutans)
      count between groups at any time interval. CONCLUSION: Both chitosan and CH were
      found to be effective in controlling plaque. However, a combination of both
      provides even better results. CLINICAL SIGNIFICANCE: The present study showed
      that chitosan can be used as an antiplaque agent.

PMID- 29358543
TI  - Role of Text Message Reminder on Oral Hygiene Maintenance of Orthodontic
      Patients.
AB  - INTRODUCTION: Fixed orthodontic treatment is frequently associated with increased
      plaque accumulation leading to gingivitis and white spot lesions (WSLs). AIM:
      This study evaluated the role of text message reminder on oral hygiene of
      orthodontic patients. MATERIALS AND METHODS: A total of 60 patients under fixed
      orthodontic treatment were randomly divided into two equal groups as control
      group and study (text message) group. Text message group received reminders about
      oral hygiene, while the control group did not receive any messages. Oral hygiene
      of both the groups was evaluated at baseline, 2, and 3 months using plaque
      indices (PIs) along with WSL status. Data were statistically analyzed using
      Statistical Package for the Social Sciences (SPSS) statistical software, version
      19, with chi-square test and t-test. RESULTS: At the baseline, plaque score was
      higher in the study group over control group (p > 0.038), whereas it was
      decreased after 3 months in the test group (p > 0.001). For WSL, there was no
      significant difference at baseline, but it was significantly lower in study group
      (p > 0.003). CONCLUSION: Oral hygiene status improved with text message reminder.

PMID- 29358544
TI  - Impact of Removable Partial Denture on Quality-of-life of Sudanese Adults in
      Khartoum State.
AB  - INTRODUCTION: Tooth loss can affect a patient's quality-of-life (QoL), impacting
      on aspects, such as nutritional intake, psychological status, self-image, and
      daily engaging in social interaction. The purpose of this study was to assess the
      oral health-related QoL (OHRQoL) among adult Sudanese patients wearing removable
      partial dentures (RPDs) by utilizing oral health impact profile-14 (OHIP-14) to
      assess patient satisfaction with their dentures. MATERIALS AND METHODS: The study
      population included 370 adult patients wearing RPDs. Of these, 99 were males and
      271 females with the age range of 35 to above 60 years. Self-reported
      questionnaires were distributed randomly to be completed by the participants from
      each health sector after having read a consent letter. Two measures interpreting
      the OHIP-14 scales (sum and prevalence) were utilized for data collection. The
      relationship of patients' demographic characteristics, general and oral health
      status, and denture characteristics with their OHRQoL was investigated. The data
      were processed and analyzed by means of Statistical Package for the Social
      Sciences (SPSS). RESULTS: The means of OHIP-14 sum and OHIP-14 prevalence of
      partial denture wearers were 10.9 + 7.8 and 18.9% respectively. The most
      problematic aspects of OHIP-14 were functional limitation and psychological
      disability. On the contrary, the participants had little problem as a handicap
      and social disability aspects. The self-reported oral health, regular follow-up,
      denture satisfaction, duration of denture wearing use of the denture while
      eating, and frequency of denture cleaning positively contribute to oral health
      related quality. CONCLUSION: Loss of teeth and use of RPD significantly affect
      patients' oral health status and QoL. Patients who are satisfied with their
      dentures have a better QoL than their unsatisfied counterparts.

PMID- 29358545
TI  - Comparative Evaluation of Remineralizing Effect of Novamin and Tricalcium
      Phosphate on Artificial Caries: An in vitro Study.
AB  - AIM: The aim of the present study was to compare the remineralizing efficacy of
      novamin and tricalcium phosphate (TCP). MATERIALS AND METHODS: Nail varnish was
      coated to a total of 30 sound human premolars except for 5 mm * 5 mm window.
      Baseline microhardness was measured for all test samples. Artificial carious
      lesions were created for all teeth by subjecting them to demineralization
      process. Then microhardness of demineralized lesion was measured. Later
      artificial caries teeth were equally divided into two groups to treat with
      remineralization solution for 10 days; group I: novamin and group II: TCP. After
      10 days of pH cycling, microhardness was measured. The data were statistically
      analyzed using Statistical Package for the Social Sciences (SPSS) statistical
      software from Chicago SPSS Inc., version 21 and using analysis of variance
      (ANOVA) post hoc multiple comparisons test for intergroup and significant
      difference at p < 0.05. RESULTS: In the present study, group I indicated a higher
      value for remineralization compared with group II (p < 0.05). CONCLUSION: The
      present study showed that both novamin and TCP were effective in remineralizing
      the carious lesions. CLINICAL SIGNIFICANCE: This study evaluates the
      remineralizing potential of novamin and TCP on initial carious lesions.

PMID- 29358546
TI  - Disinfectant Efficacy of 0.525% Sodium Hypochlorite and Epimax on Alginate
      Impression Material.
AB  - AIM: Species of Streptococcus, Escherichia coli, Staphylococcus, Actinomyces,
      Pseudomonas, Klebsiella, and Candida are commonly seen in the oral cavity.
      Impression materials are commonly contaminated with microorganisms. The present
      study was conducted to assess the disinfection efficacy of Epimax and 0.525%
      sodium hypochlorite on alginate impression over a period of 10 minutes. MATERIALS
      AND METHODS: This study was conducted in the Department of Prosthodontics in the
      year 2015. An alginate impression material was prepared. For each bacteria
      species, 15 samples were used. Out of 15 samples, 3 were used by 0.525% sodium
      hypochlorite for disinfection for 5 minutes and 3 others for 10 minutes.
      Similarly, 3 samples were used by Epimax for 5 minutes and other 3 for 10
      minutes. Three samples were used as controls. Each sample was polluted with
      Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus strains.
      RESULTS: There was no statistical difference in P. aeruginosa and C. albicans
      after 5 minutes, whereas S. aureus showed significant difference (p < 0.05).
      Epimax was found to be more effective in removing S. aureus as compared with
      other disinfectants. Both Epimax and 0.525% sodium hypochlorite did not show
      significant difference against P. aeruginosa and C. albicans, whereas significant
      difference was found between both agents against S. aureus (p < 0.05). It was
      seen that Epimax eliminated S. aureus after 5 minutes and P. aeruginosa after 10
      minutes and 99.8% C. albicans after 10 minutes. About 0.525% sodium hypochlorite
      eliminated 99.1% of C. albicans after 10 minutes, whereas 98.5 and 99% of S.
      aureus and P. aeruginosa were eliminated after 10 minutes respectively.
      CONCLUSION: Both Epimax and 0.525% sodium hypochlorite can disinfect the alginate
      impression material against C. albicans, P. aeruginosa, and S. aureus strains.
      However, Epimax was found to be more effective against S. aureus as compared with
      0.525% sodium hypochlorite. CLINICAL SIGNIFICANCE: Efficacy of disinfection of
      sodium hypo-chlorite and Epimax on alginate impression.

PMID- 29358547
TI  - Pre-endodontic Post and Core Technique for Endodontic and Prosthodontic
      Treatment.
AB  - INTRODUCTION: Displacement of provisional fixed prostheses may result in
      undesirable and embarrassing outcomes in dental treatments, especially in
      endodontic treatment. Development of certain counter measures has been necessary
      to avoid such discomforts. AIM: The aim of this report was to propose a pre
      endodontic post and core technique to achieve smooth progress of the treatment.
      MATERIALS AND METHODS: The patient was a 59-year-old male diagnosed with an
      infraocclusion caused by wear of his teeth. He received full mouth provisional
      fixed restorations for a complete oral rehabilitation. Displacement and fracture
      of the restorations frequently occurred during the observation period for the
      function of the restorations. Therefore, the pre-endodontic post and core
      technique was applied to the abutment teeth before their endodontic treatments
      were started. The technique consisted of three steps as follows: Step 1: Caries
      removal and dowel preparation were performed for the abutment teeth having apical
      periodontitis. Composite cores were indirectly fabricated, which had access holes
      for endodontic treatment. Step 2: The cores were bonded to the teeth. In
      endodontic treatment, rubber dam appliances were easily placed owing to the core,
      and proper tooth isolation was accomplished. Step 3: Fiberposts were bonded to
      the dowel holes through the access holes after the root canal filling. During
      endodontic treatment, displacement and/or fracture of the provisional
      restorations did not occur. CONCLUSION: The pre-endodontic post and core
      technique was effective in obtaining improved retention of provisional
      restoration, appropriate isolation for endodontic treatment, and sufficient
      retention of the post and core. CLINICAL SIGNIFICANCE: The pre-endodontic post
      and core technique is useful for avoiding the discomforts in dental treatments,
      namely, a smooth transition from endodontic to prosthodontic treatment can be
      achieved.

PMID- 29358548
TI  - Amar Klar: A giant among scientists (1947-2017).

PMID- 29358549
TI  - What history tells us XLIII Bacteriophage: The contexts in which it was
      discovered.

PMID- 29358550
TI  - Amalaki Rasayana improved memory and neuronal metabolic activity in AbPP-PS1
      mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder
      characterized by progressive loss of memory and cognitive function. The cerebral
      metabolic rate of glucose oxidation has been shown to be reduced in AD. The
      present study evaluated efficacy of dietary Amalaki Rasayana (AR), an Ayurvedic
      formulation used in Indian traditional system, in AbPP-PS1 mouse model of AD in
      ameliorating memory and neurometabolism, and compared with donepezil, a standard
      FDA approved drug for AD. The memory of mice was measured using Morris Water Maze
      analysis. The cerebral metabolism was followed by 13C labelling of brain amino
      acids in tissue extracts ex vivo using 1H-[13C]-NMR spectroscopy together with a
      short time infusion of [1,6-13C2]glucose to mice. The intervention with Amalaki
      Rasayana showed improved learning and memory in AbPP-PS1 mice. The 13C labelings
      of GluC4, GABAC2 and GlnC4 were reduced in AbPP-PS1 mice when compared with wild
      type controls. Intervention of AR increased the 13C labelling of amino acids
      suggesting a significant enhancement in glutamatergic and GABAergic metabolic
      activity in AbPP-PS1 mice similar to that observed with donepezil treatment.
      These data suggest that AR has potential to improve memory and cognitive function
      in AD.

PMID- 29358551
TI  - Differential reduction of reactive oxygen species by human tissuespecific
      mesenchymal stem cells from different donors under oxidative stress.
AB  - Clinical trials using human Mesenchymal Stem Cells (MSCs) have shown promising
      results in the treatment of various diseases. Different tissue sources, such as
      bone marrow, adipose tissue, dental pulp and umbilical cord, are being routinely
      used in regenerative medicine. MSCs are known to reduce increased oxidative
      stress levels in pathophysiological conditions. Differences in the ability of
      MSCs from different donors and tissues to ameliorate oxidative damage have not
      been reported yet. In this study, for the first time, we investigated the
      differences in the reactive oxygen species (ROS) reduction abilities of tissue
      specific MSCs to mitigate cellular damage in oxidative stress. Hepatic Stellate
      cells (LX-2) and cardiomyocytes were treated with Antimycin A (AMA) to induce
      oxidative stress and tissue specific MSCs were co-cultured to study the reduction
      in ROS levels. We found that both donor's age and source of tissue affected the
      ability of MSCs to reduce increased ROS levels in damaged cells. In addition, the
      abilities of same MSCs differed in LX-2 and cardiomyocytes in terms of magnitude
      of reduction of ROS, suggesting that the type of recipient cells should be kept
      in consideration when using MSCs in regenerative medicine for treatment purposes.

PMID- 29358552
TI  - Protein complex finding and ranking: An application to Alzheimer's disease.
AB  - Protein complexes are known to play a major role in controlling cellular activity
      in a living being. Identifying complexes from raw protein-protein interactions
      (PPIs) is an important area of research. Earlier work has been limited mostly to
      yeast and a few other model organisms. Such protein complex identification
      methods, when applied to large human PPIs often give poor performance. We
      introduce a novel method called ComFiR to detect such protein complexes and
      further rank diseased complexes based on a query disease. We have shown that it
      has better performance in identifying protein complexes from human PPI data. This
      method is evaluated in terms of positive predictive value, sensitivity and
      accuracy. We have introduced a ranking approach and showed its application on
      Alzheimer's disease.

PMID- 29358553
TI  - miR-200a-3p promotes b-Amyloid-induced neuronal apoptosis through down-regulation
      of SIRT1 in Alzheimer's disease.
AB  - The aberrantly expressed microRNAs (miRNAs) including miR-200a-3p have been
      reported in the brains of Alzheimer's disease (AD) patients in recent researches.
      Nevertheless, the role of miR-200a-3p in AD has not been characterized. The
      purpose of this study was to examine whether miR-200a-3p regulated beta-Ameyloid
      (A beta)-induced neuronal apoptosis by targeting SIRT1, a known anti-apoptotic
      protein. An increased level of miR-200a-3p and a decreased level of SIRT1 in the
      hippocampus of APPswe/PS delta E9 mice (a model for AD) were observed. To
      construct an in vitro cell model of AD, PC12 cells were cultured in presence of A
      beta 25-35. The results of flow cytometry analysis showed that the apoptosis rate
      and cleaved-caspase-3 expression in PC12 cells exposed to A beta 25-35 were
      remarkably increased, but the apoptosis rate and cleaved-caspase-3 activity were
      decreased when cells were transfected with anti-miR-200a-3p. On the other hand,
      MTT assay showed that the cell survival rate was increased in the A beta 25-35 +
      anti-miR-200a-3p group compared with the A beta 25-35 + anti-miR-NC group. Dual
      luciferase reporter gene assay validated the predicted miR-200a-3p binding sites
      in the 3'- UTR of SIRT1 mRNA. In addition, downregulation of SIRT1 promoted A
      beta25-35-induced neuronal apoptosis and cleavedcaspase- 3 level in PC12 cells,
      whereas anti-miR-200a-3p reversed these effects. Knockdown of SIRT1 decreased the
      inhibitory effect of A beta 25-35 on cell viability, while anti-miR-200a-3p
      attenuated this effect. Overall, the results suggest that suppression of miR-200a
      3p attenuates A beta 25-35-induced apoptosis in PC12 cells by targeting SIRT1.
      Thus, miR-200a-3p may be a potential therapeutic target for treatment of AD.

PMID- 29358555
TI  - Targeting cleavage and polyadenylation specific factor 1 via shRNA inhibits cell
      proliferation in human ovarian cancer.
AB  - Cleavage and polyadenylation specificity factor 1 (CPSF1), a member of CPSF
      complex, has been reported to play a key role in pre-mRNA 3'-end formation, but
      its possible role in ovarian cancer remains unclear. In the present study, we
      found the mRNA level of CPSF1 was overexpressed in ovarian cancer tissues using
      Oncomine Cancer Microarray database. Then the loss-of-function assays, including
      CCK-8, colony formation and flow cytometry assays, were performed to determine
      the effects of CPSF1 on cell viability, proliferation, cell cycle and apoptosis
      of human ovarian cancer cell lines (SKOV-3 and OVCAR-3). The results indicated
      that depletion of CPSF1 suppressed cell viability, impaired colony formation
      ability, induced cell cycle arrest at G0/G1 phase and promoted cell apoptosis in
      ovarian cancer cells. Furthermore, knockdown of CPSF1 upregulated the expression
      of cleaved caspase-3 and PARP and downregulated CDK4/cyclin D1 expression. These
      data suggested that CPSF1 could promote ovarian cancer cell growth and
      proliferation in vitro and its depletion might serve as a potential therapeutic
      target for human ovarian cancer.

PMID- 29358554
TI  - Knockdown of Cripto-1 inhibits the proliferation, migration, invasion, and
      angiogenesis in prostate carcinoma cells.
AB  - Cripto-1 (CR-1) is a member of the epidermal growth factor-Cripto-1/FRL1/Cryptic
      gene family that plays a key role in the various malignant cancers. However, the
      role of CR-1 in prostate carcinoma (PCa) remains limited. The expression of CR-1
      was down-regulated by small interfering RNA (siRNA). Western blot measured the
      expression levels of CR-1 and some related proteins. We performed Cell Counting
      Kit-8, 5-ethynyl-2-deoxyuridine (EdU) incorporation assay and flow cytometry to
      detect the cellular proliferation and cycle. The transwell assay was used to
      observe cellular migration and invasion. The ability of angiogenesis was
      evaluated by tube formation assay. Our results showed that CR-1 knockdown
      markedly inhibited cell proliferation and induced cycle arrest in G1 phase, as
      p21 and p27 were up-regulated, whereas cyclin D1 and cyclin E1 were diminished.
      Moreover, silencing of CR-1 dramatically inhibited cell migration and invasion,
      repressed matrix metalloproteinases, and disturbed epithelial-mesenchymal
      transition. CR-1 siRNA suppressed the secreted level of vascular endothelial
      growth factor, and reduced protein level of Vascular endothelial growth factor
      receptor 2. We further found that decreased CR-1 expression inhibited
      FAK/Src/PI3K and Wnt/b-catenin signalling in PCa cells. These results suggested
      CR-1 might be served as an effective therapeutic target in PCa.

PMID- 29358556
TI  - Cholesterol-lowering drug, in combination with chromium chloride, induces early
      apoptotic signals in intracellular L. donovani amastigotes, leading to death.
AB  - Leishmania establishes a successful parasitism by evading both oxidative and non
      oxidative killing pathways, and its drug resistance against the currently
      available therapeutics demands for a safe and cheap drug. Since the parasite
      synthesizes ergosterol instead of cholesterol, using the same biochemical pathway
      and enzymes, an inhibitor of HMG-CoA-Reductase, Lovastatin, has been tried for
      its anti-Leishmanial effect. Lovastatin, being an inhibitor of HMG-CoA-Reductase,
      inhibits infection by cholesterol depletion, while chromium chloride complexes,
      at their higher concentrations, are reported to exhibit cytotoxicity. In
      intracellular amastigotes, cytotoxicity has been checked by assessing various
      manifestation of cell death, viz. DNA fragmentation, AnnexinV-FITC binding and JC
      1 fluorescence ratio. Release of hydrogen peroxide (HPO) and nitric oxide (NO)
      has been assessed in live cell. Lovastatin and CrCl3.6H2O in combination has
      appeared to be ineffective on promastigotes but has induced cytotoxic effect on
      the intracellular amastigotes through up-regulation of cellular signalling
      mechanisms. CrCl 3.6H2O stimulates generation of NO, leading to reduction of the
      number of intracellular amastigote, while Lovastatin shows HPO-mediated killing
      of the same, keeping the host cell unaffected. This novel therapeutic approach,
      involving two known safe compounds in suboptimal doses, may resolve human
      visceral Leishmaniasis.

PMID- 29358557
TI  - Cinnamomum osmophloeum Kanehira ethanol extracts prevents human liver-derived
      HepG2 cell death from oxidation stress by induction of ghrelin gene expression.
AB  - Diabetes patients associated with liver disease carry a significant risk of
      morbidity and mortality. Cinnamon has been reported to reduce fructose-induced
      oxidative stress in the rat liver. However, the mechanism by which cinnamon
      protects the liver in a high-saccharide environment remains to be investigated.
      HepG2 cells were cultured with 30 mM D-ribose to mimic the high-oxidative-stress
      environment, typical of a liver in a diabetic patient. Three different chemical
      types of C. osmophloeum ethanol extracts (CEEs) were added in HepG2 culture media
      and the administration of all three CEEs protected HepG2 cells from D-ribose
      damage and increased cell survival by approximately 20 percent. Exclusively, the
      transcript variant 1 of the ghrelin gene, but not variant 3, was 2-3 times
      induced by the addition of these CEEs. Moreover, the mRNAs of ghrelin processing
      enzyme, furin, and mboat4 were detected in HepG2 cells. The ghrelin hormones in
      the culture media were increased 4-9 times by the addition of CEEs. The
      protective effects of ghrelin on HepG2 cells in D-ribose environment were further
      confirmed by recombinant ghrelin transfection. We conclude that the CEEs induce
      ghrelin gene expression and protect HepG2 cells from D-ribose-induced oxidative
      damage through ghrelin signalling.

PMID- 29358558
TI  - High temperatures influence sexual development differentially in male and female
      tadpoles of the Indian skipper frog, Euphlyctis cyanophlyctis.
AB  - Although sex determination in amphibians is believed to be a genetic process,
      environmental factors such as temperature are known to influence the sex
      differentiation and development. Extremely low and high temperatures influence
      gonadal development and sex ratio in amphibians but the mechanism of action is
      not known. In the present study, effect of different temperatures on gonadal
      development, sex ratio and metamorphosis was studied in the Indian skipper frog,
      Euphlyctis cyanophlyctis. The embryos of Gosner stage 7 were exposed to 20, 22,
      24, 26, 28, 30 and 32 degrees C up to tadpole stage 42. The embryos (stage 7)
      were also exposed to 20 and 32 degrees C up to tadpole stage 25 (non-feeding
      stages). Tadpoles of stage 25 were reared at 20 and 32 degrees C up to stage 42
      (feeding stages). The results show that exposure to higher temperatures (28, 30
      and 32 degrees C) during stages 7-42 produced male-biased sex ratio. Rearing of
      tadpoles at 32 degrees C during stages 25-42 produced malebiased sex ratio, while
      exposure during stages 7-25 did not affect sex ratio. Embryos and tadpoles
      exposed to lower temperatures (20 and 22 degrees C) died during the early stages.
      High temperatures stimulated testis development, and disturbed ovary development.
      Exposure to high temperatures resulted in the early metamorphosis of tadpoles
      with reduced body size. These results demonstrated that high temperatures
      influence gonadal development differently in male and female tadpoles, leading to
      male-biased sex ratio. These results suggest that high temperature probably acts
      through stress hormones and favours the small-sized sex.

PMID- 29358559
TI  - Can embryonic skipper frogs (Euphlyctis cyanophlyctis) learn to recognise
      kairomones in the absence of a nervous system?
AB  - In this study, we used larval Euphlyctis cyanophlyctis to determine the predator
      recognition mechanism. We conducted a series of experiments to determine if
      larval E. cyanophlyctis have the innate ability to recognise predatory odour
      (kairomones) as a threat or if they learn to do so during ontogeny. In the case
      of learning, we wanted to determine the developmental window during which
      learning is accomplished. Further, we tested the antipredator response of
      predator- naive as well as predator-experienced tadpoles to chemical cues of
      different origins in order to assess if they exhibit differential responses. Our
      results clearly indicate that predator-naive tadpoles of E. cyanophlyctis do not
      reduce their activity against predatory cues of dragonfly nymphs, suggesting that
      they lack the innate ability to recognise kairomones. However, they could learn
      to do so when trained to perceive kairomones simultaneously along with alarm
      cues. Surprisingly, larval E. cyanophlyctis could learn to recognise kairomones
      through association during embryonic stages even before the development of a
      nervous system. Although larval E. cyanophlyctis lack the innate ability to
      recognise kairomones, they were able to recognise conspecific alarm cues on the
      first encounter, indicating that they have the innate ability to recognise alarm
      cues as a potential threat.

PMID- 29358560
TI  - Modulation of chaperone-like and membranolytic activities of major horse seminal
      plasma protein HSP-1/2 by L-carnitine.
AB  - The major protein of horse seminal plasma, HSP-1/2, exhibits membranolytic and
      chaperone-like activities and plays a crucial role in regulating sperm
      capacitation. L-Carnitine is a small polar molecule present in high
      concentrations in mammalian seminal plasma. The present results demonstrate that
      L-carnitine binds to HSP-1/2 and increases its thermal stability, enhances
      cooperativity of its chemical unfolding and decreases both chaperone-like and
      membranolytic activities of this protein. The HSP-1/2-L-carnitine complex
      exhibits anti-oxidative behaviour by inhibiting the production of hydroxyl
      radicals, suggesting that it can protect other constituents of seminal plasma
      from damage by hydroxyl radicals. As HSP-1/2 and L-carnitine share the same
      spatiotemporal location in the horse reproductive tract, this interaction is
      physiologically significant and may prevent premature interaction of HSP-1/2 with
      sperm, which in turn regulates the sperm capacitation.

PMID- 29358561
TI  - Promoter polymorphism MMP-1 (-1607 2G/1G) and MMP-3 (-1612 5A/6A) in development
      of HAND and modulation of pathogenesis of HAND.
AB  - The pathogenesis of HIV-associated neurocognitive disorder (HAND) is modulated by
      host genetic susceptibility factors such as Matrix metalloproteinases (MMPs).
      Promoter polymorphism of MMP-1 and MMP-3 may modify the expression of the gene.
      Hence, we evaluated the association of MMP-1-16072G/1G and MMP-3-1612 5A/6A
      polymorphisms with development of HAND and the modulation of pathogenesis of
      HAND. We enrolled a total of 180 individuals, 50 HIVinfected individuals with
      HAND, 130 without HAND, and 150 healthy controls. Polymorphism of MMP-1 and MMP-3
      were genotyped by PCR-RFLP. MMP-1-1607 2G1G, -16071G/2G-1G/1G genotypes and -1607
      1G allele were associated with the development of HAND (OR = 1.64, P = 0.05; OR =
      1.45, P = 0.04; OR = 1.69, P = 0.05). MMP-1- 16071G1G, MMP-3-16125A5A genotypes
      increased the risk for the development of HAND (OR = 1.78, P = 0.25; OR = 2.39, P
      = 0.13). MMP-3-1612 5A5A, -1612 6A/5A-5A/5A genotypes and -1612 5A allele were
      associated with the reduced risk of HAND (OR = 0.40, P = 0.05; OR = 0.53, P =
      0.04; OR = 0.40, P = 0.01). Haplotype 5A1G increased the risk of development of
      HAND (OR = 1.93, P = 0.05). As observed in advanced HIV disease stage, MMP-1-1607
      1G1G genotype enhance the risk for advancement of HIV disease (OR = 1.69, P =
      0.89). MMP-3-1612 6A5A genotype showed higher risk for development of HAND in
      alcohol users (0R = 1.65, P = 0.44). MMP-1 genotype may have an influence on
      development of HAND whereas MMP3-1612 5A5A genotype may reduce risk for
      pathogenesis of HAND.

PMID- 29358562
TI  - Hypoxia stimulates invasion and migration of human cervical cancer cell lines
      HeLa/SiHa through the Rab11 trafficking of integrin alphavbeta3/FAK/PI3K pathway
      mediated Rac1 activation.
AB  - Hypoxia plays a key role in tumour cell survival, invasion, and metastasis. An
      increasing number of studies have attempted to characterize the tumour response
      to hypoxia and to identify predictive markers of disease. Here we show that
      hypoxia increases tumour cell invasion and migration by the modulation of Rab11,
      an important molecule for vesicular trafficking. In our study, we found that
      Rab11, together with the activation of Rac1, could stimulate invasion and
      migration of cervical cancer cell lines HeLa/SiHa in hypoxia. Activation of Rac1
      activity by hypoxia seems to be central to carcinoma invasion. We also found that
      these effects could be related to the integrin alphavbeta3. In addition, we
      studied the molecular pathway for this process. Our results showed that in
      cervical cancer cell lines HeLa/SiHa, Rac1 activation in hypoxia could stimulate
      invasion and migration, and this process was mediated by integrin alphavbeta3
      mediated FAK and PI3K phosphorylation. Furthermore, hypoxia induced a dramatic
      increase in alphavbeta3 integrin surface expression, and this increase is
      dependent on Rab11. In conclusion, our study might provide a new mechanism for
      the effect of hypoxia on stimulating cervical carcinoma invasion.

PMID- 29358563
TI  - Rice MYC2 (OsMYC2) modulates light-dependent seedling phenotype, disease defence
      but not ABA signalling.
AB  - Arabidopsis MYC2 (AtMYC2) is a bHLH class transcription factor that mediates
      light-dependent seedling development, disease defence, JA and ABA signalling.
      AtMYC2 gene modulates hypocotyl elongation and expression of chlorophyll A/B
      binding protein 1 (CAB1) and rubisco small subunit protein1 (RBCS1) under blue
      light. The atmyc2 mutants are resistant against virulent bacterial pathogens.
      MYC2 orthologues from several crop plants have been characterized. The rice gene
      Os10g42430 has been referred earlier as OsMYC2 and has been shown to promote
      expression of JA-inducible genes. However, the role of OsMYC2 in seedling
      development under ABA, dark or light of specific wavelengths was not known. It
      was also not known whether OsMYC2 complements AtMYC2 function in Arabidopsis. We
      show here that expression of OsMYC2 in the atmyc2 mutant of Arabidopsis
      complements the blue-light-mediated defects in hypocotyl elongation and
      expression of CAB1 and RBCS1. We generated multiple transgenic rice lines for
      over-expression and RNAi-mediated suppression of OsMYC2. In agreement with AtMYC2
      function, OsMYC2 over-expression and RNAi lines showed enhanced and suppressed
      seedling growth compared to WT plants respectively under blue light, and showed
      little effect under white light or dark. In agreement with the negative
      regulatory role of AtMYC2 in disease defence, the RNAi lines showed enhanced
      resistance against bacterial pathogen Xanthomonas oryzae pv oryzae. However, in
      contrast to AtMYC2 function, OsMYC2 influences seedling development under red
      light and show no effect in ABA-mediated seed germination. Thus, the results
      suggest evolutionarily conserved as well as the distinct role of OsMYC2 in
      comparison with AtMYC2.

PMID- 29358565
TI  - Microglia activation mediated by toll-like receptor-4 impairs brain white matter
      tracts in rats.
AB  - Microglia activation and white matter injury coexist after repeated episodes of
      mild brain trauma and ischemic stroke. Axon degeneration and demyelination can
      activate microglia; however, it is unclear whether early microglia activation can
      impair the function of white matter tracts and lead to injury. Rat corpus
      callosum (CC) slices were treated with lipopolysaccharide (LPS) or LPS +
      Rhodobacter sphaeroides (RS)-LPS that is a toll-like receptor 4 (TLR-4)
      antagonist. Functional changes reflected by the change of axon compound action
      potentials (CAPs) and the accumulation of beta-amyloid precursor protein (beta
      APP) in CC nerve fibers. Microglia activation was monitored by ionized calcium
      binding adaptor-1 immuno&fllig;uorescent stain, based on well-established
      morphological criteria and paralleled proportional area measurement. Input-output
      (I/O) curves of CAPs in response to increased stimuli were signi&filig;cantly
      downshifted in a dose-dependent manner in LPS (0.2, 0.5 and 1.0 ug/mL)-treated
      slices, implying that axons neurophysiological function was undermined. LPS
      caused signi&filig;cant beta-APP accumulation in CC tissues, re&fllig;ecting the
      deterioration of fast axon transport. LPS-induced I/O curve downshift and beta
      APP accumulation were signi&filig;cantly reversed by the pre-treatment or co
      incubation with RS-LPS. RS-LPS alone did not change the I/O curve. The degree of
      malfunction was correlated with microglia activation, as was shown by the
      measurements of proportional areas. Function of CC nerve fibers was evidently
      impaired by microglia activation and reversed by a TLP-4 antagonist, suggesting
      that the TLP-4 pathway lead to microglia activation.

PMID- 29358566
TI  - Generation and functional characterization of a conditional Pumilio2 null allele.
AB  - The highly conserved RNA binding protein PUF (Pumilio/FBF) family is present
      throughout eukaryotes from yeast to mammals, with critical roles in development,
      fertility and the nervous system. However, the function of the mammalian PUF
      family members remains underexplored. Our previous study reported that a gene
      trap mutation of Pum2 results in a smaller testis but does not impact fertility
      and viability. Although the gene-trap mutation disrupted the key functional
      domain of PUM protein-PUM-HD (Pumilio homology domain), but still produced a
      chimeric Pum2-beta-geo protein containing part of PUM2, raising a question if
      such a chimeric protein may provide any residual function or contribute to the
      reproductive phenotype. Here, we report the generation of a conditional PUM2
      allele, when knocked out, producing no residual PUM2 and hence a complete loss-of
      function allele. We also uncovered small but significant reduction of male
      fertility and viability in the mutants, suggesting requirement of PUM2 for male
      fertility and viability.

PMID- 29358564
TI  - Polymorphisms in the hepatitis C virus core and its association with development
      of hepatocellular carcinoma.
AB  - Little is known about the mechanisms underlying hepatocellular carcinoma (HCC).
      Some studies have focused on the role of HCV viral proteins in hepatocyte
      transformation. In this work we have compiled and analysed current articles
      regarding the impact of polymorphisms in the HCV core gene and protein on the
      development of HCC. An exhaustive search for fulltext articles until November
      2016 in PubMed database was performed using the MeSH keywords: 'hepatitis C',
      'polymorphisms', 'core', 'hepatocellular cancer' and 'hepatocarcinogenesis'.
      Nineteen full-text articles published between 2000 and 2016 were considered.
      Different articles associate not only the HCC development with polymorphisms at
      residues 70 and 91 in the core protein, but more with mortality and treatment
      response. Also, different polymorphisms were found in core and other viral
      proteins related to HCC development. Eleven articles reported that HCC
      development is significantly associated with Gln/His70, four associated it with
      Leu91 and two more associated it with both markers together. Additional studies
      are necessary, including those in different types of populations worldwide, to
      validate the possibility of the usability and influence in chronically HCV
      infected patients as well as to observe their interaction with other risk factors
      or prognosis and genetic markers of the host.

PMID- 29358567
TI  - Multi-Frame Super-Resolution of Gaofen-4 Remote Sensing Images.
AB  - Gaofen-4 is China's first geosynchronous orbit high-definition optical imaging
      satellite with extremely high temporal resolution. The features of staring
      imaging and high temporal resolution enable the super-resolution of multiple
      images of the same scene. In this paper, we propose a super-resolution (SR)
      technique to reconstruct a higher-resolution image from multiple low-resolution
      (LR) satellite images. The method first performs image registration in both the
      spatial and range domains. Then the point spread function (PSF) of LR images is
      parameterized by a Gaussian function and estimated by a blind deconvolution
      algorithm based on the maximum a posteriori (MAP). Finally, the high-resolution
      (HR) image is reconstructed by a MAP-based SR algorithm. The MAP cost function
      includes a data fidelity term and a regularized term. The data fidelity term is
      in the L2 norm, and the regularized term employs the Huber-Markov prior which can
      reduce the noise and artifacts while preserving the image edges. Experiments with
      real Gaofen-4 images show that the reconstructed images are sharper and contain
      more details than Google Earth ones.

PMID- 29358568
TI  - Association between Dietary Patterns of Meat and Fish Consumption with Bone
      Mineral Density or Fracture Risk: A Systematic Literature.
AB  - This systematic review aimed to investigate the association of fish and sea fish
      dietary patterns (FishDiet) and meat or processed meat dietary patterns
      (MeatDiet) with bone mineral density (BMD) and/or risk of fractures (RF). This
      review includes 37 studies with a total of 432,924 subjects. The results suggest
      that MeatDiet and FishDiet did not affect BMD or RF in 48.2% of the subjects with
      MeatDiet and in 86.5% of the subjects with FishDiet. Positive effects on bone
      were found in 3% of subjects with MeatDiet and in 12% with FishDiet. Negative
      effects on bone were observed in 2.7% of FishDiet and in 47.9% of MeatDiet. Major
      negative effects of MeatDiet were found in subjects located in the Netherlands,
      Greece, Germany, Italy, Norway, UK and Spain who do not sustain a Mediterranean
      diet (92.7%); in Korea (27.1%); in Brazil and Mexico (96.4%); and in Australia
      (62.5%). This study suggests that protein intake from fish or meat is not harmful
      to bone. Negative effects on bone linked to FishDiet are almost null. Negative
      effects on bone were associated to MeatDiet in the setting of a Western Diet but
      not in Mediterranean or Asian Diets.

PMID- 29358569
TI  - Using Impedance Measurements to Characterize Surface Modified with Gold
      Nanoparticles.
AB  - With the increased practice of preventative healthcare to help reduce costs
      worldwide, sensor technology improvement is vital to patient care. Point-of-care
      (POC) diagnostics can reduce time and lower labor in testing, and can effectively
      avoid transporting costs because of portable designs. Label-free detection allows
      for greater versatility in the detection of biological molecules. Here, we
      describe the use of an impedance-based POC biosensor that can detect changes in
      the surface modification of a micro-fabricated chip using impedance spectroscopy.
      Gold nanoparticles (GNPs) have been employed to evaluate the sensing ability of
      our new chip using impedance measurements. Furthermore, we used impedance
      measurements to monitor surface functionalization progress on the sensor's
      interdigitated electrodes (IDEs). Electrodes made from aluminum and gold were
      employed and the results were analyzed to compare the impact of electrode
      material. GNPs coated with mercaptoundecanoic acid were also used as a model of
      biomolecules to greatly enhance chemical affinity to the silicon substrate. The
      portable sensor can be used as an alternative technology to ELISA (enzyme-linked
      immunosorbent assays) and polymerase chain reaction (PCR)-based techniques. This
      system has advantages over PCR and ELISA both in the amount of time required for
      testing and the ease of use of our sensor. With other techniques, larger,
      expensive equipment must be utilized in a lab environment, and procedures have to
      be carried out by trained professionals. The simplicity of our sensor system can
      lead to an automated and portable sensing system.

PMID- 29358570
TI  - Long Non-Coding RNA Cancer Susceptibility Candidate 2a (CASC2a) Is a Marker of
      Early Recurrence After Radical Cystectomy in Patients with Urothelial Carcinoma
      of the Bladder.
AB  - BACKGROUND The aim of this study was to investigate the expression of long non
      coding RNAs (lncRNA) cancer susceptibility candidate 2a (CASC2a) in patients with
      urothelial carcinoma of the bladder (UCB) and its predictive value in the
      recurrence of UCB after radical cystectomy (RC). MATERIAL AND METHODS Tumor and
      paired adjacent normal tissues were obtained from 112 patients with UCB who
      underwent RC in our hospital from March 2010 to March 2012. The expression of
      CASC2a was evaluated by quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR) and fluorescence in situ hybridization (FISH). RESULTS CASC2a
      was down-regulated in UCB tissues, and was highly negatively correlated with the
      pT, pN, tumor size, and lymphovascular invasion (LVI). The sensitivities of
      CASC2a for diagnosing UCB and its recurrence after RC were 89.30% and 81.55%,
      respectively, and the specificities were 71.43% and 58.21%, respectively.
      Patients with a high expression of CASC2a had a higher 5-year recurrence-free
      survival rate than those with low expression of CASC2a. Kaplan-Meier survival
      analysis demonstrated that the pT, pN, tumor grade, tumor size, concomitant
      carcinoma in situ (CIS), LVI, soft tissue surgical margin (STSM), and CASC2a
      expression were related to the recurrence in patients undergoing RC for UCB. Cox
      proportional hazard model analysis showed that CASC2 expression, pT4, lymph node
      metastasis, and CIS were independent risk factors. CONCLUSIONS CASC2a was down
      regulated in patients with UCB, and was associated with the risk of recurrence
      among patients undergoing RC, indicating that lncRNAs could act as predictive
      biomarkers and potential therapeutic targets in bladder cancer, including CASC2a.

PMID- 29358571
TI  - A Bone Conduction Implantable Device as a Functional Treatment Option in
      Unilateral Microtia with Bilateral Stapes Ankylosis: A Report of Two Cases.
AB  - BACKGROUND Implantable devices have been proposed as an alternative to hearing
      aids and auditory canal reconstruction in patients with microtia (congenital
      aural atresia), which includes a malformation of the external and middle ear.
      This report is of two rare cases of microtia associated with congenital stapes
      ankylosis treated with an implantable device and describes the treatment
      outcomes. CASE REPORT Two siblings from Ecuador, a 29-year-old woman, and her 35
      year-old brother, were born with unilateral type II microtia with bilateral
      external auditory canal atresia and conductive hearing loss. Pre-operatively,
      high-resolution computed tomography (HRCT) imaging was performed using FastView
      software to allow placement of a bone conduction-floating mass transducer (BC
      FMT) to couple a Bonebridge bone conduction implant (BCI) system in both
      patients. Pure-tone audiometry (PTA) testing and speech audiology were performed.
      The Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Speech, Spatial
      and Qualities (SSQ) of hearing scale questionnaires and scoring systems were
      used. Following activation of the implantable device, both patients achieved
      improved bilateral conductive hearing with sound-field (field-free) thresholds
      >25 dB, and speech recognition scores >90%. In both cases, hearing improvement
      remained at three years following surgery. CONCLUSIONS To our knowledge, these
      are the first reported cases of microtia with congenital stapes ankylosis
      successfully treated with a bone conduction implantable device. Patients with
      microtia and stapes ankylosis who are reluctant to undergo surgery may benefit
      from unilateral or bilateral, short-term or long-term use of a Bonebridge bone
      conduction implantable device.

PMID- 29358574
TI  - Publisher Correction: The low affinity neurotrophin receptor CD271 regulates
      phenotype switching in melanoma.
AB  - The originally published version of this Article was updated shortly after
      publication to add the words 'The' and 'affinity' to the title, following their
      inadvertent removal during the production process. This has now been corrected in
      both the PDF and HTML versions of the Article.

PMID- 29358572
TI  - Pharmacokinetic Drug-Drug Interactions Between Immunosuppressant and Anti
      Infective Agents: Antimetabolites and Corticosteroids.
AB  - Infections account for 15-20% of deaths in transplant recipients, requiring rapid
      and appropriate therapeutic interventions. Many anti-infective agents interact
      with immunosuppressive regimens used in transplantation, placing patients at
      increased risk for adverse drug reactions and prolonged hospitalizations. There
      is established data regarding the level of evidence and magnitude of interactions
      between calcineurin inhibitors and mammalian target of rapamycin inhibitors with
      anti-infective agents. Less is known about the interactions with anti
      proliferative agents and corticosteroids, with gaps in knowledge on the
      appropriate management of these interactions. The objective of this review was to
      highlight the pharmacokinetic drug-drug interactions between antimetabolites and
      corticosteroids with commonly used anti-infective agents.

PMID- 29358573
TI  - Unwrapping the genomic characteristics of urothelial bladder cancer and successes
      with immune checkpoint blockade therapy.
AB  - Urothelial bladder cancer (UBC) is one of the most common lethal cancer worldwide
      and the 5-year survival rate has not improved significantly with current
      treatment protocols during the last decade. Intravesical immunotherapy with
      Bacillus Calmette-Guerin is currently the standard care for non-muscle invasive
      UBC. Recently, a subset of patients with locally advanced or metastatic UBC have
      responded to checkpoint blockade immunotherapy against the programmed cell death
      1 protein (PD-1) or its ligand (PD-L1) or the cytotoxic T-lymphocyte antigen 4
      that releases the inhibition of T cells, the remarkable clinical efficacy on UBC
      has brought total five checkpoint inhibitors approved by the FDA in the last 2
      years, and this is revolutionizing treatment of advanced UBC. We discuss the
      rationale for immunotherapy in bladder cancer, progress with blocking the PD-1/PD
      L1 pathway for UBC treatment, and ongoing clinical trials. We highlight the
      complexity of the interactions between cancer cells and the immune system, the
      genomic basis for response to checkpoint blockade immunotherapy, and potential
      biomarkers for predicting immunotherapeutic response.

PMID- 29358575
TI  - Pathological hydrogen peroxide triggers the fibrillization of wild-type SOD1 via
      sulfenic acid modification of Cys-111.
AB  - Amyotrophic lateral sclerosis (ALS) involves the abnormal posttranslational
      modifications and fibrillization of copper, zinc superoxide dismutase (SOD1) and
      TDP-43. However, how SOD1-catalyzed reaction product hydrogen peroxide affects
      amyloid formation of SOD1 and TDP-43 remains elusory. 90% of ALS cases are
      sporadic and the remaining cases are familial ALS. In this paper, we demonstrate
      that H2O2 at pathological concentrations triggers the fibrillization of wild-type
      SOD1 both in vitro and in SH-SY5Y cells. Using an anti-dimedone antibody that
      detects sulfenic acid modification of proteins, we found that Cys-111 in wild
      type SOD1 is oxidized to C-SOH by pathological concentration of H2O2, followed by
      the formation of sulfenic acid modified SOD1 oligomers. Furthermore, we show that
      such SOD1 oligomers propagate in a prion-like manner, and not only drive wild
      type SOD1 to form fibrils in the cytoplasm but also induce cytoplasm
      mislocalization and the subsequent fibrillization of wild-type TDP-43, thereby
      inducing apoptosis of living cells. Thus, we propose that H2O2 at pathological
      concentrations triggers the fibrillization of wild-type SOD1 and subsequently
      induces SOD1 toxicity and TDP-43 toxicity in neuronal cells via sulfenic acid
      modification of Cys-111 in SOD1. Our Western blot and ELISA data demonstrate that
      sulfenic acid modified wild-type SOD1 level in cerebrospinal fluid of 15 sporadic
      ALS patients is significantly increased compared with 6 age-matched control
      patients. These findings can explain how H2O2 at pathologic concentrations
      regulates the misfolding and toxicity of SOD1 and TDP-43 associated with ALS, and
      suggest that sulfenic acid modification of wild-type SOD1 should play pivotal
      roles in the pathogenesis of sporadic ALS.

PMID- 29358576
TI  - Impairment of Fas-ligand-caveolin-1 interaction inhibits Fas-ligand translocation
      to rafts and Fas-ligand-induced cell death.
AB  - Fas-ligand/CD178 belongs to the TNF family proteins and can induce apoptosis
      through death receptor Fas/CD95. The important requirement for Fas-ligand
      dependent cell death induction is its localization to rafts, cholesterol- and
      sphingolipid-enriched micro-domains of membrane, involved in regulation of
      different signaling complexes. Here, we demonstrate that Fas-ligand physically
      associates with caveolin-1, the main protein component of rafts. Experiments with
      cells overexpressing Fas-ligand revealed a FasL N-terminal pre-prolin-rich
      region, which is essential for the association with caveolin-1. We found that the
      N-terminal domain of Fas-ligand bears two caveolin-binding sites. The first
      caveolin-binding site binds the N-terminal domain of caveolin-1, whereas the
      second one appears to interact with the C-terminal domain of caveolin-1. The
      deletion of both caveolin-binding sites in Fas-ligand impairs its distribution
      between cellular membranes, and attenuates a Fas-ligand-induced cytotoxicity.
      These results demonstrate that the interaction of Fas-ligand and caveolin-1
      represents a molecular basis for Fas-ligand translocation to rafts, and the
      subsequent induction of Fas-ligand-dependent cell death. A possibility of a
      similar association between other TNF family members and caveolin-1 is discussed.

PMID- 29358577
TI  - TACC3 transcriptionally upregulates E2F1 to promote cell growth and confer
      sensitivity to cisplatin in bladder cancer.
AB  - Accumulating evidence has shown that transforming acidic coiled-coil 3 (TACC3) is
      deregulated in a broad spectrum of cancers. In the present study, we reported
      that TACC3 was markedly elevated in bladder cancer, especially in muscle-invasive
      bladder cancers (MIBCs). The upregulation of TACC3 was positively associated with
      tumor invasiveness, grade, T stage, and progression in patients with bladder
      cancer. Furthermore, a Kaplan-Meier survival analysis showed that patients with
      bladder cancer whose tumors had high TACC3 expression experienced a dismal
      prognosis compared with patients whose tumors had low TACC3 expression.
      Functional studies have found that TACC3 is a prerequisite for the development of
      malignant characteristics of bladder cancer cells, including cell proliferation
      and invasion. Moreover, TACC3 promoted G1/S transition, which was mediated via
      activation of the transcription of E2F1, eventually enhancing cell proliferation.
      Notably, the overexpression of TACC3 or E2F1 indicates a high sensitivity to
      cisplatin. Taken together, these findings define a tumor-supportive role for
      TACC3, which may also serve as a prognostic and therapeutic indicator in bladder
      cancers.

PMID- 29358578
TI  - Culex pipiens crossing type diversity is governed by an amplified and polymorphic
      operon of Wolbachia.
AB  - Culex pipiens mosquitoes are infected with Wolbachia (wPip) that cause an
      important diversity of cytoplasmic incompatibilities (CIs). Functional transgenic
      studies have implicated the cidA-cidB operon from wPip and its homolog in wMel in
      CI between infected Drosophila males and uninfected females. However, the genetic
      basis of the CI diversity induced by different Wolbachia strains was unknown. We
      show here that the remarkable diversity of CI in the C. pipiens complex is due to
      the presence, in all tested wPip genomes, of several copies of the cidA-cidB
      operon, which undergoes diversification through recombination events. In 183
      isofemale lines of C. pipiens collected worldwide, specific variations of the
      cidA-cidB gene repertoires are found to match crossing types. The diversification
      of cidA-cidB is consistent with the hypothesis of a toxin-antitoxin system in
      which the gene cidB co-diversifies with the gene cidA, particularly in putative
      domains of reciprocal interactions.

PMID- 29358579
TI  - Structural basis of thalidomide enantiomer binding to cereblon.
AB  - Thalidomide possesses two optical isomers which have been reported to exhibit
      different pharmacological and toxicological activities. However, the precise
      mechanism by which the two isomers exert their different activities remains
      poorly understood. Here, we present structural and biochemical studies of (S)-
      and (R)-enantiomers bound to the primary target of thalidomide, cereblon (CRBN).
      Our biochemical studies employed deuterium-substituted thalidomides to suppress
      optical isomer conversion, and established that the (S)-enantiomer exhibited ~10
      fold stronger binding to CRBN and inhibition of self-ubiquitylation compared to
      the (R)-enantiomer. The crystal structures of the thalidomide-binding domain of
      CRBN bound to each enantiomer show that both enantiomers bind the tri-Trp pocket,
      although the bound form of the (S)-enantiomer exhibited a more relaxed
      glutarimide ring conformation. The (S)-enantiomer induced greater teratogenic
      effects on fins of zebrafish compared to the (R)-enantiomer. This study has
      established a mechanism by which thalidomide exerts its effects in a
      stereospecific manner at the atomic level.

PMID- 29358581
TI  - Simple and cost-effective method of highly conductive and elastic carbon
      nanotube/polydimethylsiloxane composite for wearable electronics.
AB  - The development of various flexible and stretchable materials has attracted
      interest for promising applications in biomedical engineering and electronics
      industries. This interest in wearable electronics, stretchable circuits, and
      flexible displays has created a demand for stable, easily manufactured, and cheap
      materials. However, the construction of flexible and elastic electronics, on
      which commercial electronic components can be mounted through simple and cost
      effective processing, remains challenging. We have developed a nanocomposite of
      carbon nanotubes (CNTs) and polydimethylsiloxane (PDMS) elastomer. To achieve
      uniform distributions of CNTs within the polymer, an optimized dispersion process
      was developed using isopropyl alcohol (IPA) and methyl-terminated PDMS in
      combination with ultrasonication. After vaporizing the IPA, various shapes and
      sizes can be easily created with the nanocomposite, depending on the mold. The
      material provides high flexibility, elasticity, and electrical conductivity
      without requiring a sandwich structure. It is also biocompatible and mechanically
      stable, as demonstrated by cytotoxicity assays and cyclic strain tests (over
      10,000 times). We demonstrate the potential for the healthcare field through
      strain sensor, flexible electric circuits, and biopotential measurements such as
      EEG, ECG, and EMG. This simple and cost-effective fabrication method for CNT/PDMS
      composites provides a promising process and material for various applications of
      wearable electronics.

PMID- 29358580
TI  - PI3K induces B-cell development and regulates B cell identity.
AB  - Phosphoinositide-3 kinase (PI3K) signaling is important for the survival of
      numerous cell types and class IA of PI3K is specifically required for the
      development of B cells but not for T cell development. Here, we show that class
      IA PI3K-mediated signals induce the expression of the transcription factor Pax5,
      which plays a central role in B cell commitment and differentiation by activating
      the expression of central B cell-specific signaling proteins such as SLP-65 and
      CD19. Defective class IA PI3K function leads to reduction in Pax5 expression and
      prevents B cell development beyond the stage expressing the precursor B cell
      receptor (pre-BCR). Investigating the mechanism of PI3K-induced Pax5 expression
      revealed that it involves a network of transcription factors including FoxO1 and
      Irf4 that directly binds to the Pax5 gene. Together, our results suggest that
      PI3K signaling links survival and differentiation of developing B cells with B
      cell identity and that decreased PI3K activity in pre-B cells results in reduced
      Pax5 expression and lineage plasticity.

PMID- 29358582
TI  - Evolutionary analyses of myosin genes in trypanosomatids show a history of
      expansion, secondary losses and neofunctionalization.
AB  - Myosins are motor proteins that comprise a large and diversified family important
      for a broad range of functions. Two myosin classes, I and XIII, were previously
      assigned in Trypanosomatids, based mainly on the studies of Trypanosoma cruzi, T.
      brucei and Leishmania major, and important human pathogenic species; seven orphan
      myosins were identified in T. cruzi. Our results show that the great variety of
      T. cruzi myosins is also present in some closely related species and in Bodo
      saltans, a member of an early divergent branch of Kinetoplastida. Therefore,
      these myosins should no longer be considered "orphans". We proposed the
      classification of a kinetoplastid-specific myosin group into a new class, XXXVI.
      Moreover, our phylogenetic data suggest that a great repertoire of myosin genes
      was present in the last common ancestor of trypanosomatids and B. saltans, mainly
      resulting from several gene duplications. These genes have since been
      predominantly maintained in synteny in some species, and secondary losses explain
      the current distribution. We also found two interesting genes that were clearly
      derived from myosin genes, demonstrating that possible redundant or useless
      genes, instead of simply being lost, can serve as raw material for the evolution
      of new genes and functions.

PMID- 29358583
TI  - A stand-alone fiber-coupled single-photon source.
AB  - In this work, we present a stand-alone and fiber-coupled quantum-light source.
      The plug-and-play device is based on an optically driven quantum dot delivering
      single photons via an optical fiber. The quantum dot is deterministically
      integrated in a monolithic microlens which is precisely coupled to the core of an
      optical fiber via active optical alignment and epoxide adhesive bonding. The
      rigidly coupled fiber-emitter assembly is integrated in a compact Stirling
      cryocooler with a base temperature of 35 K. We benchmark our practical quantum
      device via photon auto-correlation measurements revealing g(2)(0) = 0.07 +/- 0.05
      under continuous-wave excitation and we demonstrate triggered non-classical light
      at a repetition rate of 80 MHz. The long-term stability of our quantum light
      source is evaluated by endurance tests showing that the fiber-coupled quantum dot
      emission is stable within 4% over several successive cool-down/warm-up cycles.
      Additionally, we demonstrate non-classical photon emission for a user
      intervention-free 100-hour test run and stable single-photon count rates up to
      11.7 kHz with a standard deviation of 4%.

PMID- 29358584
TI  - Nitrogen cycling during secondary succession in Atlantic Forest of Bahia, Brazil.
AB  - Carbon accumulation in tropical secondary forests may be limited in part by
      nitrogen (N) availability, but changes in N during tropical forest succession
      have rarely been quantified. We explored N cycle dynamics across a chronosequence
      of secondary tropical forests in the Mata Atlantica of Bahia, Brazil in order to
      understand how quickly the N cycle recuperates. We hypothesized that N fixation
      would decline over the course of succession as N availability and N gaseous
      losses increased. We measured N fixation, KCl-extractable N, net mineralization
      and nitrification, resin-strip sorbed N, gaseous N emissions and the soil
      delta15N in stands that were 20, 35, 50, and > 50 years old. Contrary to our
      initial hypothesis, we found no significant differences between stand ages in any
      measured variable. Our findings suggest that secondary forests in this region of
      the Atlantic forest reached pre-disturbance N cycling dynamics after just 20
      years of succession. This result contrasts with previous study in the Amazon,
      where the N cycle recovered slowly after abandonment from pasture reaching pre
      disturbance N cycling levels after ~50 years of succession. Our results suggest
      the pace of the N cycle, and perhaps tropical secondary forest, recovery, may
      vary regionally.

PMID- 29358585
TI  - Emergence of a substrate-temperature-dependent dielectric process in a
      prototypical vapor deposited hole-transport glass.
AB  - Since the discovery of ultrastability, vapor deposition has emerged as a relevant
      tool to further understand the nature of glasses. By this route, the density and
      average orientation of glasses can be tuned by selecting the proper deposition
      conditions. Dielectric spectroscopy, on the other hand, is a basic technique to
      study the properties of glasses at a molecular level, probing the dynamics of
      dipoles or charge carriers. Here, and for the first time, we explore the
      dielectric behavior of vapor deposited N,N-Diphenyl-N,N'bis(methylphenyl)-1,1'
      biphenyl-4,4'-diamines (TPD), a prototypical hole-transport material, prepared at
      different deposition temperatures. We report the emergence of a new relaxation
      process which is not present in the ordinary glass. We associate this process to
      the Maxwell-Wagner polarization observed in heterogeneous systems, and induced by
      the enhanced mobility of charge carriers in the more ordered vapor deposited
      glasses. Furthermore, the associated activation energy establishes a clear
      distinction between two families of glasses, depending on the selected substrate
      temperature range. This finding positions dielectric spectroscopy as a unique
      tool to investigate the structural and electronic properties of charge transport
      materials and remarks the importance of controlling the deposition conditions,
      historically forgotten in the preparation of optoelectronic devices.

PMID- 29358586
TI  - Hydroclimatic conditions trigger record harmful algal bloom in western Patagonia
      (summer 2016).
AB  - A harmful algal bloom (HAB) of the raphidophyta alga Pseudochattonella cf.
      verruculosa during the 2016 austral summer (February-March) killed nearly 12% of
      the Chilean salmon production, causing the worst mass mortality of fish and
      shellfish ever recorded in the coastal waters of western Patagonia. The HAB
      coincided with a strong El Nino event and the positive phase of the Southern
      Annular Mode that altered the atmospheric circulation in southern South America
      and the adjacent Pacific Ocean. This led to very dry conditions and higher than
      normal solar radiation reaching the surface. Using time series of atmospheric,
      hydrologic and oceanographic data we show here that an increase in surface water
      temperature and reduced freshwater input resulted in a weakening of the vertical
      stratification in the fjords and sounds of this region. This allowed the
      advection of more saline and nutrient-rich waters, ultimately resulting in an
      active harmful algal bloom in coastal southern Chile.

PMID- 29358587
TI  - Gender-specific associations of skeletal muscle mass and arterial stiffness among
      peritoneal dialysis patients.
AB  - Decreased skeletal muscle has been identified as a relevant factor for arterial
      stiffness but has not been thoroughly investigated in peritoneal dialysis (PD)
      patients. The aim of this study was to investigate the relationship between
      skeletal muscle and arterial stiffness in PD patients. A cross-sectional study of
      658 prevalent PD patients with a mean brachial-ankle pulse wave velocity (baPWV)
      of 1714 (+/-501) cm/s and mean skeletal muscle mass of 26.6 (+/-5.4) kg was
      performed. Skeletal muscle mass level was significantly higher in males than in
      females. When examining skeletal muscle mass as a continuous variable, skeletal
      muscle mass was significantly associated with baPWV in fully adjusted linear
      regression models in total patients [standardized coefficients (beta), -0.181;
      95% confidence interval (95% CI), -0.276 to -0.056; P = 0.003] or female patients
      (beta, -0.119; 95% CI, -0.350 to -0.015; P = 0.03) but not in male patients
      (beta, -0.117; 95% CI, -0.300 to 0.011; P = 0.07). Furthermore, in females, a
      significant association between the middle or highest tertile of skeletal muscle
      mass and baPWV was found in fully adjusted models (beta, -0.123; 95% CI, -0.204
      to -0.008; P = 0.03; beta, -0.140; 95% CI, -0.228 to -0.016; P = 0.02,
      respectively). In conclusion, decreased skeletal muscle mass was independently
      associated with increased baPWV in PD patients, and this association was
      significant in females but not in males.

PMID- 29358588
TI  - Enhanced Ductility of PEEK thin film with self-assembled fibre-like crystals.
AB  - Poly Ether Ether Ketone (PEEK) is a high temperature polymer material known for
      its excellent chemical resistance, high strength and toughness. As a semi
      crystalline polymer, PEEK can become very brittle during long crystallisation
      times and temperatures helped as well by its high content of rigid benzene rings
      within its chemical structure. This paper presents a simple quench
      crystallization method for preparation of PEEK thin films with the formation of a
      novel fibre-like crystal structure on the surface of the films. These quenched
      crystallised films show higher elongation at break when compared with
      conventional melt crystallised thin films incorporating spherulitic crystals,
      while the tensile strength of both types of films (quenched crystallised and
      conventional melt) remained the same. The fracture analysis carried out using
      microscopy revealed an interesting microstructure which evolves as a function of
      annealing time. Based on these results, a crystal growth mechanism describing the
      development of the fibre-like crystals on the surface of the quenched
      crystallised films is proposed.

PMID- 29358589
TI  - GGA2 interacts with EGFR cytoplasmic domain to stabilize the receptor expression
      and promote cell growth.
AB  - Epidermal growth factor receptor (EGFR) signaling and its downregulation upon
      ligand binding have been extensively documented. However, the mechanisms by which
      cells maintain steady-state EGFR expression remain poorly understood. Here, we
      report a novel role of Golgi-localized, gamma-adaptin ear-containing, ADP
      ribosylation factor-binding protein 2 (GGA2) in the control of EGFR turnover.
      Whereas GGA1- or GGA3-depletion increased EGFR expression, GGA2-depletion by RNAi
      greatly reduced steady-state expression of EGFR, reflecting enhanced lysosomal
      degradation of EGFR. Subsequent pull-down assays showed interactions of VHS-GAT
      domains from three GGAs with the cytoplasmic juxtamembrane region (jxt) of EGFR,
      which was dependent on N108 in the VHS domain. Proximity ligation assay also
      revealed the steady-state interaction between GGA2 and EGFR in situ. Moreover,
      reduced expression of EGFR in GGA2-depleted cells was reversed by additional
      depletion of GGA1 or GGA3, suggesting that GGA1 and GGA3 promote EGFR
      degradation. In addition, GGA2-depleted cells had reduced EGF signaling and cell
      proliferation in cell culture and xenograft experiments. Finally, GGA2 was
      upregulated in 30.8% of human hepatocellular carcinomas and 23.3% of colorectal
      cancers. Together, these results indicate that GGA2 supports cell growth by
      interacting with EGFR for sustaining the receptor expression.

PMID- 29358590
TI  - New Insight into Mixing Fluoride and Chloride in Bioactive Silicate Glasses.
AB  - Adding fluoride into bioactive glasses leads to fluorapatite formation and a
      decrease in glass transition temperature. Recently, chloride has been introduced
      into glasses as an alternative to fluoride. The presence of the large chloride
      ion lowers glass crystallisation tendency and increases glass molar volume, which
      effectively facilitates glass degradation and bone-bonding apatite-like layer
      formation. However, there is no information regarding the effect of mixing
      fluoride and chloride on the glass structure and properties. This study aims to
      synthesize mixed fluoride and chloride containing bioactive glasses; investigate
      the structural role of fluoride and chloride and their effects on glass
      properties. The chloride content measurements reveal that 77-90% of chloride was
      retained in these Q2 type glasses. Glass transition temperature reduced markedly
      with an increase in CaX2 (X = F + Cl) content, while the glass molar volume
      increased. 29Si MAS-NMR results show that the incorporation of mixed fluoride and
      chloride did not cause significant change in the polymerization of the silicate
      network and no detectable concentration of Si-F/Cl bands were present. This
      agrees with 19F NMR spectra showing that F existed as F-Ca(n) species.

PMID- 29358591
TI  - Grazing and climate effects on soil organic carbon concentration and particle
      size association in northern grasslands.
AB  - Grasslands cover more than 40% of the terrestrial surface of Earth and provide a
      range of ecological goods and services, including serving as one of the largest
      reservoirs for terrestrial carbon. An understanding of how livestock grazing,
      influences grassland soil organic carbon (SOC), including its concentration,
      vertical distribution and association among soil-particle sizes is unclear. We
      quantified SOC concentrations in the upper 30 cm of mineral soil, together with
      SOC particle-size association, within 108 pairs of long-term grazed and non
      grazed grassland study sites spanning six distinct climate subregions across a
      5.7 M ha area of Alberta, Canada. Moderate grazing enhanced SOC concentration by
      12% in the upper 15 cm of soil. Moreover, SOC concentrations in mineral layers
      were associated with regional climate, such that SOC increased from dry to mesic
      subregions. Our results also indicate that C concentrations in each of 2000-250,
      250-53, < 53 MUm soil particle-size fractions were consistent with total SOC
      concentrations, increasing from semi-arid to more mesic subregions. We conclude
      that long-term livestock grazing may enhance SOC concentrations in shallow
      mineral soil and affirm that climate rather than grazing is the key modulator of
      soil C storage across northern grasslands.

PMID- 29358592
TI  - Aversive gustatory learning and perception in honey bees.
AB  - Taste perception allows discriminating edible from non-edible items and is
      crucial for survival. In the honey bee, the gustatory sense has remained largely
      unexplored, as tastants have been traditionally used as reinforcements rather
      than as stimuli to be learned and discriminated. Here we provide the first
      characterization of antennal gustatory perception in this insect using a novel
      conditioning protocol in which tastants are dissociated from their traditional
      food-reinforcement role to be learned as predictors of punishment. We found that
      bees have a limited gustatory repertoire via their antennae: they discriminate
      between broad gustatory modalities but not within modalities, and are unable to
      differentiate bitter substances from water. Coupling gustatory conditioning with
      blockade of aminergic pathways in the bee brain revealed that these pathways are
      not restricted to encode reinforcements but may also encode conditioned stimuli.
      Our results reveal unknown aspects of honey bee gustation, and bring new elements
      for comparative analyses of gustatory perception in animals.

PMID- 29358593
TI  - Defining the Akt1 interactome and its role in regulating the cell cycle.
AB  - Cell growth and proliferation are two diverse processes yet always linked. Akt1,
      a serine/threonine kinase, is a multi-functional protein implicated in regulation
      of cell growth, survival and proliferation. Though it has a role in G1/S
      progression, the manner by which Akt1 controls cell cycle and blends cell growth
      with proliferation is not well explored. In this study, we characterize the Akt1
      interactome as the cell cycle progresses from G0 to G1/S and G2 phase. For this,
      Akt1-overexpressing HEK293 cells were subjected to AP-MS. To distinguish between
      individual cell cycle stages, cells were cultured in the light, medium and heavy
      labelled SILAC media. We obtained 213 interacting partners of Akt1 from these
      studies. GO classification revealed that a significant number of proteins fall
      into functional classes related to cell growth or cell cycle processes. Of these,
      32 proteins showed varying association with Akt1 in different cell cycle stages.
      Further analyses uncovered a subset of proteins showing counteracting effects so
      as to tune stage-specific progression through the cycle. Thus, our study provides
      some novel perspectives on Akt1-mediated regulation of the cell cycle and offers
      the framework for a detailed resolution of the downstream cellular mechanisms
      that are mediated by this kinase.

PMID- 29358594
TI  - Intra-retinal Arterial Cannulation using a Microneedle for Central Retinal Artery
      Occlusion.
AB  - Central retinal artery occlusion (CRAO) is a severe disease, often causing
      blindness. We evaluated the efficacy and safety of a surgical procedure for the
      treatment of acute CRAO in which retinal arterial cannulation with tissue
      plasminogen activator (tPA) is performed. The surgical procedure consisted of
      vitrectomy followed by cannulation of the central retinal artery and injection of
      tPA (200 MUg) using a 47-gauge microneedle. Thirteen CRAO patients were treated
      within 48 hours of the onset of symptoms. The central retinal artery of all 13
      eyes was successfully cannulated. The mean interval between the onset of symptoms
      and surgery was 38.7 hours. The results for all 13 eyes treated showed a
      statistically significant improvement in mean visual acuity between before and
      one month after treatment (-1.60 vs. -0.82 logarithmic values for minimum angle
      resolution (LogMAR), p = 0.0021). Fluorescein angiography showed complete
      reperfusion and incomplete reperfusion in 10 eyes and 3 eyes, respectively.
      Recently developed surgical instruments have made retinal-arterial cannulation
      feasible. Intra-retinal-arterial cannulation has potential as a method of
      improving visual function and microcirculation in eyes affected by CRAO.

PMID- 29358596
TI  - Tunable band-gap structure and gap solitons in the generalized Gross-Pitaevskii
      equation with a periodic potential.
AB  - The tunable band-gap structure is fundamentally important in the dynamics of both
      linear and nonlinear modes trapped in a lattice because Bloch modes can only
      exist in the bands of the periodic system and nonlinear modes associating with
      them are usually confined to the gaps. We reveal that when a momentum operator is
      introduced into the Gross-Pitaevskii equation (GPE), the bandgap spectra of the
      periodic system can be shifted upward parabolically by the growth of the constant
      momentum coefficient. During this process, the band edges become asymmetric, in
      sharp contrast to the standard GPE with an external periodic potential. Extended
      complex Bloch modes with asymmetric profiles can be derived by applying a phase
      transformation to the symmetric profiles. We find that the inherent parity-time
      symmetry of the complex system is never broken with increasing momentum
      coefficient. Under repulsive interactions, solitons with different numbers of
      peaks bifurcating from the band edges are found in finite gaps. We also address
      the existence of embedded solitons in the generalized two-dimensional GPE. Linear
      stability analysis corroborated by direct evolution simulations demonstrates that
      multi-peaked solitons are almost completely stable in their entire existence
      domains.

PMID- 29358595
TI  - An Injectable Oxygen Release System to Augment Cell Survival and Promote Cardiac
      Repair Following Myocardial Infarction.
AB  - Oxygen deficiency after myocardial infarction (MI) leads to massive cardiac cell
      death. Protection of cardiac cells and promotion of cardiac repair are key
      therapeutic goals. These goals may be achieved by re-introducing oxygen into the
      infarcted area. Yet current systemic oxygen delivery approaches cannot
      efficiently diffuse oxygen into the infarcted area that has extremely low blood
      flow. In this work, we developed a new oxygen delivery system that can be
      delivered specifically to the infarcted tissue, and continuously release oxygen
      to protect the cardiac cells. The system was based on a thermosensitive,
      injectable and fast gelation hydrogel, and oxygen releasing microspheres. The
      fast gelation hydrogel was used to increase microsphere retention in the heart
      tissue. The system was able to continuously release oxygen for 4 weeks. The
      released oxygen significantly increased survival of cardiac cells under the
      hypoxic condition (1% O2) mimicking that of the infarcted hearts. It also reduced
      myofibroblast formation under hypoxic condition (1% O2). After implanting into
      infarcted hearts for 4 weeks, the released oxygen significantly augmented cell
      survival, decreased macrophage density, reduced collagen deposition and
      myofibroblast density, and stimulated tissue angiogenesis, leading to a
      significant increase in cardiac function.

PMID- 29358597
TI  - Mitochondrial genome diversity and population structure of two western honey bee
      subspecies in the Republic of South Africa.
AB  - Apis mellifera capensis Eschscholtz and A.m. scutellata Lepeletier are subspecies
      of western honey bees that are indigenous to the Republic of South Africa (RSA).
      Both subspecies have invasive potential and are organisms of concern for areas
      outside their native range, though they are important bees to beekeepers,
      agriculture, and the environment where they are native. The aim of the present
      study was to examine genetic differentiation among these subspecies and estimate
      their phylogenetic relationships using complete mitochondrial genomes sequences.
      We used 25 individuals that were either assigned to one of the subspecies or
      designated hybrids using morphometric analyses. Phylogenetic analyses of
      mitogenome sequences by maximum likelihood (ML) and Bayesian inference identified
      a monophyletic RSA clade, subdivided into two clades. A haplotype network was
      consistent with the phylogenetic trees. However, members of both subspecies
      occurred in both clades, indicating that A.m. capensis and A.m. scutellata are
      neither reciprocally monophyletic nor do they exhibit paraphyly with one
      subspecies nested within the other subspecies. Furthermore, no mitogenomic
      features were diagnostic to either subspecies. All bees analyzed from the RSA
      expressed a substantial level of haplotype diversity (most samples had unique
      haplotypes) but limited nucleotide diversity. The number of variable codons
      across protein-coding genes (PCGs) differed among loci, with CO3 exhibiting the
      most variation and ATP6 the least.

PMID- 29358598
TI  - Spin orbit torques induced magnetization reversal through asymmetric domain wall
      propagation in Ta/CoFeB/MgO structures.
AB  - The magnetization reversal induced by spin orbit torques in the presence of
      Dzyaloshinskii-Moriya interaction (DMI) in perpendicularly magnetized
      Ta/CoFeB/MgO structures were investigated by using a combination of Anomalous
      Hall effect measurement and Kerr effect microscopy techniques. By analyzing the
      in-plane field dependent spin torque efficiency measurements, an effective field
      value for the DMI of ~300 Oe was obtained, which plays a key role to stabilize
      Neel walls in the film stack. Kerr imaging reveals that the current-induced
      reversal under small and medium in-plane field was mediated by domain nucleation
      at the edge of the Hall bar, followed by asymmetric domain wall (DW) propagation.
      However, as the in-plane field strength increases, an isotropic DW expansion was
      observed before reaching complete reversal. Micromagnetic simulations of the DW
      structure in the CoFeB layer suggest that the DW configuration under the combined
      effect of the DMI and the external field is responsible for the various DW
      propagation behaviors.

PMID- 29358599
TI  - Specific Upregulation of a Cotton Phytoene Synthase Gene Produces Golden
      Cottonseeds with Enhanced Provitamin A.
AB  - Provitamin A (PVA) bio-fortification of crops offers a sustainable strategy to
      prevent the prevalence of vitamin A deficiency (VAD), one of the world's major
      public health problems. The present work aimed to enhance PVA accumulation in
      cottonseed, the main by-product in the production of cotton fibers and the third
      largest source of edible plant oil in the world. On the basis of comprehensive
      identification of carotenoid synthase genes and their expression levels in
      various cotton tissues, we selected phytoene synthase as the target for
      manipulating carotenoid biosynthesis in the developing cottonseeds. After
      functional verification in transgenic tobacco, a cotton phytoene synthase gene
      (GhPSY2D) driven by a seed-specific promoter was transformed into cotton. The
      transgenic cottonseeds showed golden appearance and contained over 6-fold higher
      carotenoid contents in the extracted oil than the non-transgenic control. Thin
      layer chromatograph analysis indicated that the main PVA carotenoid beta-carotene
      was predominant in the transgenic cottonseeds, but undetectable in the wild-type
      control. By simultaneously providing economically valuable fibers and edible
      oils, the transgenic cottons bio-fortified with beta-carotene in seeds may be a
      new powerful tool against VAD in low-income regions.

PMID- 29358600
TI  - Cost-utility of allogeneic hematopoietic stem cell transplantation in Norway.

PMID- 29358601
TI  - Syngeneic hematopoietic stem cell transplantation from HTLV-1 seropositive twin
      for adult T-cell leukemia-lymphoma.

PMID- 29358602
TI  - Influence of gestational weight gain on low birth weight in short-statured South
      Indian pregnant women.
AB  - BACKGROUND/OBJECTIVES: India contributes to one-third of the global burden of low
      birth weight (LBW) neonates, which is associated with increased risk of mortality
      and adverse consequences on long-term health. Factors leading to LBW are
      multidimensional and maternal short stature is an important component with an
      inter-generational effect. On the contrary gestational weight gain (GWG) shows an
      independent positive influence on birth weight. The aim of the present study
      therefore was to determine the influence of GWG on birth weight in short pregnant
      women. SUBJECTS/METHODS: A prospective observational cohort of 1254 pregnant
      women was studied. Total, second and third trimester GWG per week were computed.
      Women were divided into two groups, "short" and "not-short", using a cut off of
      152 cm that corresponded to the 25th percentile for height in the cohort.
      Association of tertiles of GWG with LBW was examined using log binomial
      regression analysis. RESULTS: "Short" women in highest tertile of total GWG had a
      significantly reduced adjusted relative risk (ARR 0.37, 95% confidence interval
      0.16-0.83, P = 0.016) for LBW, compared to the lowest tertile. However, there was
      no significant increase in risk for cesarean section (CS) with increasing
      tertiles of total GWG. CONCLUSIONS: In women with height <152 cm a significant
      reduced risk for LBW was observed with the greatest total GWG, without a
      significant increase in the risk for CS. This suggests that improving GWG in
      short women may be beneficial for the birth weight of the offspring.

PMID- 29358603
TI  - Status and determinants of intra-household food allocation in rural Nepal.
AB  - BACKGROUND/OBJECTIVES: Understanding of the patterns and predictors of intra
      household food allocation could enable nutrition programmes to better target
      nutritionally vulnerable individuals. This study aims to characterise the status
      and determinants of intra-household food and nutrient allocation in Nepal.
      SUBJECTS/METHODS: Pregnant women, their mothers-in-law and male household heads
      from Dhanusha and Mahottari districts in Nepal responded to 24-h dietary recalls,
      thrice repeated on non-consecutive days (n = 150 households; 1278 individual
      recalls). Intra-household inequity was measured using ratios between household
      members in food intakes (food shares); food-energy intake proportions ('food
      shares-to-energy shares', FS:ES); calorie-requirement proportions ('relative
      dietary energy adequacy ratios', RDEARs) and mean probability of adequacy for 11
      micronutrients (MPA ratios). Hypothesised determinants were collected during the
      recalls, and their associations with the outcomes were tested using multivariable
      mixed-effects linear regression models. RESULTS: Women's diets (pregnant women
      and mothers-in-law) consisted of larger FS:ES of starchy foods, pulses, fruits
      and vegetables than male household heads, whereas men had larger FS:ES of animal
      source foods. Pregnant women had the lowest MPA (37%) followed by their mothers
      in-law (52%), and male household heads (57%). RDEARs between pregnant women and
      household heads were 31% higher (log-RDEAR coeff=0.27 (95% CI 0.12, 0.42), P <
      0.001) when pregnant women earned more or the same as their spouse, and log-MPA
      ratios between pregnant women and mothers-in-law were positively associated with
      household-level calorie intakes (coeff=0.43 (0.23, 0.63), P < 0.001, per 1000
      kcal). CONCLUSIONS: Pregnant women receive inequitably lower shares of food and
      nutrients, but this could be improved by increasing pregnant women's cash
      earnings and household food security.

PMID- 29358604
TI  - Southern Ocean warming and Wilkes Land ice sheet retreat during the mid-Miocene.
AB  - Observations and model experiments highlight the importance of ocean heat in
      forcing ice sheet retreat during the present and geological past, but past ocean
      temperature data are virtually missing in ice sheet proximal locations. Here we
      document paleoceanographic conditions and the (in)stability of the Wilkes Land
      subglacial basin (East Antarctica) during the mid-Miocene (~17-13.4 million years
      ago) by studying sediment cores from offshore Adelie Coast. Inland retreat of the
      ice sheet, temperate vegetation, and warm oligotrophic waters characterise the
      mid-Miocene Climatic Optimum (MCO; 17-14.8 Ma). After the MCO, expansion of a
      marine-based ice sheet occurs, but remains sensitive to melting upon episodic
      warm water incursions. Our results suggest that the mid-Miocene latitudinal
      temperature gradient across the Southern Ocean never resembled that of the
      present day. We demonstrate that a strong coupling of oceanic climate and
      Antarctic continental conditions existed and that the East Antarctic subglacial
      basins were highly sensitive to ocean warming.

PMID- 29358605
TI  - Molecular fossils from organically preserved Ediacara biota reveal cyanobacterial
      origin for Beltanelliformis.
AB  - The Ediacara biota (~575-541 million years ago) mark the emergence of large,
      complex organisms in the palaeontological record, preluding the radiation of
      modern animal phyla. However, their phylogenetic relationships, even at the
      domain level, remain controversial. We report the discovery of molecular fossils
      from organically preserved specimens of Beltanelliformis, demonstrating that they
      represent large spherical colonies of cyanobacteria. The conservation of
      molecular remains in organically preserved Ediacaran organisms opens a new path
      for unravelling the natures of the Ediacara biota.

PMID- 29358606
TI  - Hook innovation boosts foraging efficiency in tool-using crows.
AB  - The New Caledonian crow is the only non-human animal known to craft hooked tools
      in the wild, but the ecological benefit of these relatively complex tools remains
      unknown. Here, we show that crows acquire food several times faster when using
      hooked rather than non-hooked tools, regardless of tool material, prey type and
      extraction context. This implies that small changes to tool shape can strongly
      affect energy-intake rates, highlighting a powerful driver for technological
      advancement.

PMID- 29358607
TI  - Community proteogenomics reveals the systemic impact of phosphorus availability
      on microbial functions in tropical soil.
AB  - Phosphorus is a scarce nutrient in many tropical ecosystems, yet how soil
      microbial communities cope with growth-limiting phosphorus deficiency at the gene
      and protein levels remains unknown. Here, we report a metagenomic and
      metaproteomic comparison of microbial communities in phosphorus-deficient and
      phosphorus-rich soils in a 17-year fertilization experiment in a tropical forest.
      The large-scale proteogenomics analyses provided extensive coverage of many
      microbial functions and taxa in the complex soil communities. A greater than
      fourfold increase in the gene abundance of 3-phytase was the strongest response
      of soil communities to phosphorus deficiency. Phytase catalyses the release of
      phosphate from phytate, the most recalcitrant phosphorus-containing compound in
      soil organic matter. Genes and proteins for the degradation of phosphorus
      containing nucleic acids and phospholipids, as well as the decomposition of
      labile carbon and nitrogen, were also enhanced in the phosphorus-deficient soils.
      In contrast, microbial communities in the phosphorus-rich soils showed increased
      gene abundances for the degradation of recalcitrant aromatic compounds,
      transformation of nitrogenous compounds and assimilation of sulfur. Overall,
      these results demonstrate the adaptive allocation of genes and proteins in soil
      microbial communities in response to shifting nutrient constraints.

PMID- 29358608
TI  - Potentially dangerous consequences for biodiversity of solar geoengineering
      implementation and termination.
AB  - Solar geoengineering is receiving increased policy attention as a potential tool
      to offset climate warming. While climate responses to geoengineering have been
      studied in detail, the potential biodiversity consequences are largely unknown.
      To avoid extinction, species must either adapt or move to track shifting
      climates. Here, we assess the effects of the rapid implementation, continuation
      and sudden termination of geoengineering on climate velocities-the speeds and
      directions that species would need to move to track changes in climate. Compared
      to a moderate climate change scenario (RCP4.5), rapid geoengineering
      implementation reduces temperature velocities towards zero in terrestrial
      biodiversity hotspots. In contrast, sudden termination increases both ocean and
      land temperature velocities to unprecedented speeds (global medians >10 km yr-1)
      that are more than double the temperature velocities for recent and future
      climate change in global biodiversity hotspots. Furthermore, as climate
      velocities more than double in speed, rapid climate fragmentation occurs in
      biomes such as temperate grasslands and forests where temperature and
      precipitation velocity vectors diverge spatially by >90 degrees . Rapid
      geoengineering termination would significantly increase the threats to
      biodiversity from climate change.

PMID- 29358609
TI  - Biodiversity risks of climate control.

PMID- 29358610
TI  - A southern African origin and cryptic structure in the highly mobile plains
      zebra.
AB  - The plains zebra (Equus quagga) is an ecologically important species of the
      African savannah. It is also one of the most numerous and widely distributed
      ungulates, and six subspecies have been described based on morphological
      variation. However, the within-species evolutionary processes have been difficult
      to resolve due to its high mobility and a lack of consensus regarding the
      population structure. We obtained genome-wide DNA polymorphism data from more
      than 167,000 loci for 59 plains zebras from across the species range,
      encompassing all recognized extant subspecies, as well as three mountain zebras
      (Equus zebra) and three Grevy's zebras (Equus grevyi). Surprisingly, the
      population genetic structure does not mirror the morphology-based subspecies
      delineation, underlining the dangers of basing management units exclusively on
      morphological variation. We use demographic modelling to provide insights into
      the past phylogeography of the species. The results identify a southern African
      location as the most likely source region from which all extant populations
      expanded around 370,000 years ago. We show evidence for inclusion of the extinct
      and phenotypically divergent quagga (Equus quagga quagga) in the plains zebra
      variation and reveal that it was less divergent from the other subspecies than
      the northernmost (Ugandan) extant population.

PMID- 29358611
TI  - Exome-wide analysis of mutational burden in patients with typical and atypical
      Rolandic epilepsy.
AB  - Rolandic epilepsy (RE) is the most common focal epilepsy in childhood. To date no
      hypothesis-free exome-wide mutational screen has been conducted for RE and
      atypical RE (ARE). Here we report on whole-exome sequencing of 194 unrelated
      patients with RE/ARE and 567 ethnically matched population controls. We
      identified an exome-wide significantly enriched burden for deleterious and loss
      of-function variants only for the established RE/ARE gene GRIN2A. The statistical
      significance of the enrichment disappeared after removing ARE patients. For
      several disease-related gene-sets, an odds ratio >1 was detected for loss-of
      function variants.

PMID- 29358612
TI  - Whole-sequence analysis indicates that the Y chromosome C2*-Star Cluster traces
      back to ordinary Mongols, rather than Genghis Khan.
AB  - The Y-chromosome haplogroup C3*-Star Cluster (revised to C2*-ST in this study)
      was proposed to be the Y-profile of Genghis Khan. Here, we re-examined the origin
      of C2*-ST and its associations with Genghis Khan and Mongol populations. We
      analyzed 34 Y-chromosome sequences of haplogroup C2*-ST and its most closely
      related lineage. We redefined this paternal lineage as C2b1a3a1-F3796 and
      generated a highly revised phylogenetic tree of the haplogroup, including 36 sub
      lineages and 265 non-private Y-chromosome variants. We performed a comprehensive
      analysis and age estimation of this lineage in eastern Eurasia, including 18,210
      individuals from 292 populations. We discovered that the origin of populations
      with high frequencies of C2*-ST can be traced to either an ancient Niru'un Mongol
      clan or ordinary Mongol tribes. Importantly, the age of the most recent common
      ancestor of C2*-ST (2576 years, 95% CI = 1975-3178) and its sub-lineages, and
      their expansion patterns, are consistent with the diffusion of all Mongolic
      speaking populations, rather than Genghis Khan himself or his close male
      relatives. We concluded that haplogroup C2*-ST is one of the founder paternal
      lineages of all Mongolic-speaking populations, and direct evidence of an
      association between C2*-ST and Genghis Khan has yet to be discovered.

PMID- 29358613
TI  - Key apoptotic genes APAF1 and CASP9 implicated in recurrent folate-resistant
      neural tube defects.
AB  - Neural tube defects (NTDs) remain one of the most serious birth defects, and
      although genes in several pathways have been implicated as risk factors for
      neural tube defects via knockout mouse models, very few molecular causes in
      humans have been identified. Whole exome sequencing identified deleterious
      variants in key apoptotic genes in two families with recurrent neural tube
      defects. Functional studies in fibroblasts indicate that these variants are loss
      of-function, as apoptosis is significantly reduced. This is the first report of
      variants in apoptotic genes contributing to neural tube defect risk in humans.

PMID- 29358614
TI  - Congenital diaphragmatic hernia as a part of Nance-Horan syndrome?
AB  - Nance-Horan syndrome is a rare X-linked developmental disorder characterized by
      bilateral congenital cataract, dental anomalies, facial dysmorphism, and
      intellectual disability. Here, we identify a patient with Nance-Horan syndrome
      caused by a new nonsense NHS variant. In addition, the patient presented
      congenital diaphragmatic hernia. NHS gene expression in murine fetal diaphragm
      was demonstrated, suggesting a possible involvement of NHS in diaphragm
      development. Congenital diaphragmatic hernia could result from NHS loss of
      function in pleuroperitoneal fold or in somites-derived muscle progenitor cells
      leading to an impairment of their cells migration.

PMID- 29358615
TI  - Neuromyopathy with congenital cataracts and glaucoma: a distinct syndrome caused
      by POLG variants.
AB  - We identified three non-related patients manifesting a childhood-onset
      progressive neuromyopathy with congenital cataracts, delayed walking, distal
      weakness and wasting, glaucoma and swallowing difficulties. Electrophysiology and
      nerve biopsies showed a mixed axonal and demyelinating neuropathy, while muscle
      biopsy disclosed both neurogenic and myopathic changes with ragged red fibers,
      and muscle MRI showed consistent features across patients, with a peculiar
      concentric disto-proximal gradient of fatty replacement. We used targeted next
      generation sequencing and candidate gene approach to study these families.
      Compound biallelic heterozygous variants, p.[(Pro648Arg)]; [(His932Tyr)] and
      p.[(Thr251Ile),(Pro587Leu)]; [(Arg943Cys)], were found in the three patients
      causing this homogeneous phenotype. Our report on a subset of unrelated patients,
      that showed a distinct autosomal recessive childhood-onset neuromyopathy with
      congenital cataracts and glaucoma, expands the clinical spectrum of POLG-related
      disorders. It also confirms the association between cataracts and neuropathy with
      variants in POLG. Early onset cataract is otherwise rare in POLG-related
      disorders and so far reported only in a few patients with the clinical pattern of
      distal myopathy or neuromyopathy.

PMID- 29358616
TI  - Identification of 22q13 genes most likely to contribute to Phelan McDermid
      syndrome.
AB  - Chromosome 22q13.3 deletion (Phelan McDermid) syndrome (PMS) is a rare genetic
      neurodevelopmental disorder resulting from deletions or other genetic variants on
      distal 22q. Pathological variants of the SHANK3 gene have been identified, but
      terminal chromosomal deletions including SHANK3 are most common. Terminal
      deletions disrupt up to 108 protein-coding genes. The impact of these losses is
      highly variable and includes both significantly impairing neurodevelopmental and
      somatic manifestations. The current review combines two metrics, prevalence of
      gene loss and predicted loss pathogenicity, to identify likely contributors to
      phenotypic expression. These genes are grouped according to function as follows:
      molecular signaling at glutamate synapses, phenotypes involving neuropsychiatric
      disorders, involvement in multicellular organization, cerebellar development and
      functioning, and mitochondrial. The likely most impactful genes are reviewed to
      provide information for future clinical and translational investigations.

PMID- 29358617
TI  - Ex Vivo Tracer Efficacy in Optical Imaging of Staphylococcus Aureus Nuclease
      Activity.
AB  - The key to effective treatment of bacterial infections is a swift and reliable
      diagnosis. Current clinical standards of bacterial diagnosis are slow and
      laborious. There are several anatomical imaging modalities that can detect
      inflammation, but none can distinguish between bacterial and sterile
      inflammation. Novel tracers such as smart activatable fluorescent probes
      represent a promising development that allow fast and specific testing without
      the use of ionizing radiation. Previously, a smart activatable probe was
      developed that is a substrate for the micrococcal nuclease as produced by
      Staphylococcus aureus. In the present study, the function of this probe was
      validated. Practical applicability in terms of sensitivity was assessed by
      incubation of the probe with 26 clinical S. aureus isolates, and probe
      specificity was verified by incubation with 30 clinical isolates and laboratory
      strains of various bacterial pathogens. The results show that the nuclease
      specific probe was activated by all tested S. aureus isolates and laboratory
      strains with a threshold of ~106-107 cells/mL. The probe was also activated by
      certain opportunistic staphylococci. We therefore propose that the studied
      nuclease probe represents a significant step forward to address the need for a
      rapid, practical, and precise method to detect infections caused by S. aureus.

PMID- 29358618
TI  - EZH2 mutations in chronic myelomonocytic leukemia cluster with ASXL1 mutations
      and their co-occurrence is prognostically detrimental.

PMID- 29358619
TI  - Novel therapeutic strategy for cervical cancer harboring FGFR3-TACC3 fusions.
AB  - We previously found that therapeutic targetable fusions are detected across
      various cancers. To identify therapeutic targetable fusion in uterine cervical
      cancer, for which no effective gene targeted therapy has yet been clinically
      applied, we analyzed RNA sequencing data from 306 cervical cancer samples. We
      detected 445 high confidence fusion transcripts and identified four samples that
      harbored FGFR3-TACC3 fusion as an attractive therapeutic target. The frequency of
      FGFR3-TACC3-fusion-positive cervical cancer is also 1.9% (2/103) in an
      independent cohort. Continuous expression of the FGFR3-TACC3 fusion transcript
      and protein induced anchorage-independent growth in the cervical epithelial cell
      line established from the ectocervix (Ect1/E6E7) but not in that from endocervix
      (End1/E6E7). Injection of FGFR3-TACC3 fusion-transfected-Ect1/E6E7 cells
      subcutaneously into NOG mice generated squamous cell carcinoma xenograft tumors,
      suggesting the association between FGFR3-TACC3 fusion and squamous cell
      carcinogenesis. Transfection of a FGFR3-TACC3 fusion transcript into four
      cervical cancer cell lines (SiHa, ME180, HeLa, and Ca Ski) induced activation of
      the MAPK pathway and enhancement of cell proliferation. Transcriptome analysis of
      the FGFR3-TACC3 fusion-transfected cell lines revealed that an IL8-triggered
      inflammatory response was increased, via activation of FGFR3-MAPK signaling.
      Continuous expression of FGFR3-TACC3 fusion led to activation of the PI3K-AKT
      pathway only in the two cell lines that harbored PIK3CA mutations. Sensitivity to
      the FGFR inhibitor, BGJ398, was found to depend on PIK3CA mutation status. Dual
      inhibition of both FGFR and AKT showed an obvious synergistic effect in cell
      lines that harbor mutant PIK3CA. Additionally, TACC3 inhibitor, KHS101,
      suppressed FGFR3-TACC3 fusion protein expression and showed antitumor effect
      against FGFR3-TACC3 fusion-transfected cell lines. FGFR3-TACC3 fusion-positive
      cancer has frequent genetic alterations of the PI3K/AKT pathway and selection of
      appropriate treatment based on PI3K/AKT pathway status should be required.

PMID- 29358621
TI  - Hollow nanostructures of metal oxides as next generation electrode materials for
      supercapacitors.
AB  - Hollow nanostructures of copper oxides help to stabilize appreciably higher
      electrochemical characteristics than their solid counter parts of various
      morphologies. The specific capacitance values, calculated using cyclic
      voltammetry (CV) and charge-discharge (CD) studies, are found to be much higher
      than the values reported in literature for copper oxide particles showing 
      intriguing morphologies or even composites with trendy systems like CNTs, rGO,
      graphene, etc. The proposed cost-effective synthesis route makes these materials
      industrially viable for application in alternative energy storage devices. The
      improved electrochemical response can be attributed to effective access to the
      higher number of redox sites that become available on the surface, as well as in
      the cavity of the hollow particles. The ion transport channels also facilitate
      efficient de-intercalation, which results in the enhancement of cyclability and
      Coulombic efficiency. The charge storage mechanism in copper oxide structures is
      also proposed in the paper.

PMID- 29358620
TI  - The high molecular weight dipeptidyl peptidase IV Pol d 3 is a major allergen of
      Polistes dominula venom.
AB  - Hymenoptera venom allergy can cause severe anaphylaxis in untreated patients.
      Polistes dominula is an important elicitor of venom allergy in Southern Europe as
      well as in the United States. Due to its increased spreading to more moderate
      climate zones, Polistes venom allergy is likely to gain importance also in these
      areas. So far, only few allergens of Polistes dominula venom were identified as
      basis for component-resolved diagnostics. Therefore, this study aimed to broaden
      the available panel of important Polistes venom allergens. The 100 kDa allergen
      Pol d 3 was identified by mass spectrometry and found to be a dipeptidyl
      peptidase IV. Recombinantly produced Pol d 3 exhibited sIgE-reactivity with
      approximately 66% of Polistes venom-sensitized patients. Moreover, its clinical
      relevance was supported by the potent activation of basophils from allergic
      patients. Cross-reactivity with the dipeptidyl peptidases IV from honeybee and
      yellow jacket venom suggests the presence of exclusive as well as conserved IgE
      epitopes. The obtained data suggest a pivotal role of Pol d 3 as sensitizing
      component of Polistes venom, thus supporting its status as a major allergen of
      clinical relevance. Therefore, Pol d 3 might become a key element for proper
      diagnosis of Polistes venom allergy.

PMID- 29358622
TI  - Effects of soil water and heat relationship under various snow cover during
      freezing-thawing periods in Songnen Plain, China.
AB  - In this study, the spatial variations of soil water and heat under bare land
      (BL), natural snow (NS), compacted snow (CS) and thick snow (TS) treatments were
      analyzed. The relationship curve between soil temperature and water content
      conforms to the exponential filtering model, by means of the functional form of
      the model, it was defined as soil water and heat relation function model. On this
      basis, soil water and heat function models of 10, 20, 40, 60, 100, and 140 cm
      were established. Finally, a spatial variation law of the relationship effect was
      described based on analysising of the differences between the predicted and
      measured results. During freezing period, the effects of external factors on soil
      were hindered by snow cover. As the snow increased, the accuracy of the function
      model gradually improved. During melting period, infiltration by snowmelt
      affected the relationship between the soil temperature and moisture. With the
      increasing of snow, the accuracy of the function models gradually decreased. The
      relationship effects of soil water and heat increased with increasing depth
      within the frozen zone. In contrast, below the frozen layer, the relationship of
      soil water and heat was weaker, and the function models were less accurate.

PMID- 29358623
TI  - Targeted reduction of the EGFR protein, but not inhibition of its kinase
      activity, induces mitophagy and death of cancer cells through activation of
      mTORC2 and Akt.
AB  - The oncogenic epidermal growth factor receptor (EGFR) is commonly overexpressed
      in solid cancers. The tyrosine kinase activity of EGFR has been a major
      therapeutic target for cancer; however, the efficacy of EGFR tyrosine kinase
      inhibitors to treat cancers has been challenged by innate and acquired resistance
      at the clinic. Accumulating evidence suggests that EGFR possesses kinase
      independent pro-survival functions, and that cancer cells are more vulnerable to
      reduction of EGFR protein than to inhibition of its kinase activity. The
      molecular mechanism underlying loss-of-EGFR-induced cell death remains largely
      unknown. In this study, we show that, unlike inhibiting EGFR kinase activity that
      is known to induce pro-survival non-selective autophagy, downregulating EGFR
      protein, either by siRNA, or by a synthetic EGFR-downregulating peptide
      (Herdegradin), kills prostate and ovarian cancer cells via selective mitophagy by
      activating the mTORC2/Akt axis. Furthermore, Herdegradin induced mitophagy and
      inhibited the growth of orthotopic ovarian cancers in mice. This study identifies
      anti-mitophagy as a kinase-independent function of EGFR, reveals a novel function
      of mTORC2/Akt axis in promoting mitophagy in cancer cells, and offers a novel
      approach for pharmacological downregulation of EGFR protein as a potential
      treatment for EGFR-positive cancers.

PMID- 29358624
TI  - Long-acting injectable atovaquone nanomedicines for malaria prophylaxis.
AB  - Chemoprophylaxis is currently the best available prevention from malaria, but its
      efficacy is compromised by non-adherence to medication. Here we develop a long
      acting injectable formulation of atovaquone solid drug nanoparticles that confers
      long-lived prophylaxis against Plasmodium berghei ANKA malaria in C57BL/6 mice.
      Protection is obtained at plasma concentrations above 200 ng ml-1 and is causal,
      attributable to drug activity against liver stage parasites. Parasites that
      appear after subtherapeutic doses remain atovaquone-sensitive. Pharmacokinetic
      pharmacodynamic analysis indicates protection can translate to humans at
      clinically achievable and safe drug concentrations, potentially offering
      protection for at least 1 month after a single administration. These findings
      support the use of long-acting injectable formulations as a new approach for
      malaria prophylaxis in travellers and for malaria control in the field.

PMID- 29358625
TI  - Understanding the effect of wet etching on damage resistance of surface
      scratches.
AB  - Fused silica optics often exhibit surface scratches after polishing that
      radically reduce their damage resistance at the wavelength of 351 nm in the
      nanosecond regime. Consequently, chemical treatments after polishing are often
      used to increase the damage threshold and ensure a safe operation of these optics
      in large fusion-scale laser facilities. Here, we investigate the reasons for such
      an improvement. We study the effect of an HF-based wet etching on scratch
      morphology and propose a simple analytic model to reflect scratch widening during
      etching. We also use a finite element model to evaluate the effect of the
      morphological modification induced by etching on the electric field distribution
      in the vicinity of the scratch. We evidence that this improvement of the scratch
      damage resistance is due to a reduction of the electric field enhancement. This
      conclusion is supported by secondary electron microscopy (SEM) imaging of damage
      sites initiated on scratches after chemical treatment.

PMID- 29358626
TI  - Anti-Hermitian photodetector facilitating efficient subwavelength photon sorting.
AB  - The ability to split an incident light beam into separate wavelength bands is
      central to a diverse set of optical applications, including imaging, biosensing,
      communication, photocatalysis, and photovoltaics. Entirely new opportunities are
      currently emerging with the recently demonstrated possibility to spectrally split
      light at a subwavelength scale with optical antennas. Unfortunately, such small
      structures offer limited spectral control and are hard to exploit in
      optoelectronic devices. Here, we overcome both challenges and demonstrate how
      within a single-layer metafilm one can laterally sort photons of different
      wavelengths below the free-space diffraction limit and extract a useful
      photocurrent. This chipscale demonstration of anti-Hermitian coupling between
      resonant photodetector elements also facilitates near-unity photon-sorting
      efficiencies, near-unity absorption, and a narrow spectral response (~ 30 nm) for
      the different wavelength channels. This work opens up entirely new design
      paradigms for image sensors and energy harvesting systems in which the active
      elements both sort and detect photons.

PMID- 29358627
TI  - Predictability of Intraocular Lens Power Calculation for Cataract with
      Keratoconus: A Multicenter Study.
AB  - This study was aimed to assess the predictability of intraocular lens (IOL) power
      calculation after cataract surgery for keratoconus. We retrospectively reviewed
      the clinical charts of 102 eyes of 71 consecutive keratoconic patients who
      developed cataract. We determined manifest spherical equivalent, prediction
      errors, and absolute errors, 1 month postoperatively. The achieved refraction was
      significantly more hyperopic than the targeted refraction, when keratometric
      readings were used (p = 0.001). At 1 month, 36% and 63% of the eyes were within
      +/-0.5 and +/-1.0 D, respectively, of the targeted correction. We found a
      significant correlation between the prediction error and the mean keratometry
      (Pearson correlation coefficient r =-0.545, p < 0.001). No vision-threatening
      complications occurred in any case. The achieved refraction was significantly
      more myopic than the targeted refraction, when total corneal refractive power was
      used (p = 0.013). Phacoemulsification with IOL implantation appeared to be safe
      and effective, and the accuracy was also good in mild keratoconus, but not in
      severe keratoconus. It should be noted that that a large amount of hyperopic
      shift occurred especially in advanced keratoconic patients, when keratometric
      readings were used for IOL power calculation, and that a slight, but significant,
      myopic shift occurred, when total corneal refractive power was used.

PMID- 29358628
TI  - Characterization of Carbon-Contaminated B4C-Coated Optics after Chemically
      Selective Cleaning with Low-Pressure RF Plasma.
AB  - Boron carbide (B4C) is one of the few materials that is expected to be most
      resilient with respect to the extremely high brilliance of the photon beam
      generated by free electron lasers (FELs) and is thus of considerable interest for
      optical applications in this field. However, as in the case of many other optics
      operated at light source facilities, B4C-coated optics are subject to ubiquitous
      carbon contaminations. Carbon contaminations represent a serious issue for the
      operation of FEL beamlines due to severe reduction of photon flux, beam
      coherence, creation of destructive interference, and scattering losses. A variety
      of B4C cleaning technologies were developed at different laboratories with
      varying success. We present a study regarding the low-pressure RF plasma cleaning
      of carbon contaminated B4C test samples via inductively coupled O2/Ar, H2/Ar, and
      pure O2 RF plasma produced following previous studies using the same ibss GV10x
      downstream plasma source. Results regarding the chemistry, morphology as well as
      other aspects of the B4C optical coating before and after the plasma cleaning are
      reported. We conclude that among the above plasma processes only plasma based on
      pure O2 feedstock gas exhibits the required chemical selectivity for maintaining
      the integrity of the B4C optical coatings.

PMID- 29358631
TI  - High geothermal heat flux in close proximity to the Northeast Greenland Ice
      Stream.
AB  - The Greenland ice sheet (GIS) is losing mass at an increasing rate due to surface
      melt and flow acceleration in outlet glaciers. Currently, there is a large
      disagreement between observed and simulated ice flow, which may arise from
      inaccurate parameterization of basal motion, subglacial hydrology or geothermal
      heat sources. Recently it was suggested that there may be a hidden heat source
      beneath GIS caused by a higher than expected geothermal heat flux (GHF) from the
      Earth's interior. Here we present the first direct measurements of GHF from
      beneath a deep fjord basin in Northeast Greenland. Temperature and salinity time
      series (2005-2015) in the deep stagnant basin water are used to quantify a GHF of
      93 +/- 21 mW m-2 which confirm previous indirect estimated values below GIS. A
      compilation of heat flux recordings from Greenland show the existence of
      geothermal heat sources beneath GIS and could explain high glacial ice speed
      areas such as the Northeast Greenland ice stream.

PMID- 29358630
TI  - Core promoter information content correlates with optimal growth temperature.
AB  - The subtle mechanisms by which protein-DNA interactions remain functional across
      a wide range of temperatures are largely unknown. In this work, we manually
      curated available information relating fully sequenced archaeal genomes with
      organism growth temperatures. We built a motif that represents the core promoter
      of each species and calculated its information content. We then studied the
      relation between optimal growth temperature (OGT) and information content (IC) in
      the promoter region.We found a positive correlation between G + C content and OGT
      in tRNA regions and not in overall genome. Furthermore, we found that there is a
      positive correlation between information content and optimal growth temperatures
      in Archaea. This can't be explained by an increased C+G composition nor by other
      obvious mechanisms. These findings suggest that increased information content
      could produce a positive fitness in organisms living at high temperatures. We
      suggest that molecular information theory may need to be adapted for
      hyperthermophiles.

PMID- 29358632
TI  - CCR5/CCL5 axis interaction promotes migratory and invasiveness of pancreatic
      cancer cells.
AB  - Pancreatic cancer (PC) is one of the deadliest cancers and remains a major
      challenge due to its invasive and metastatic nature. Increased levels of CCR5 and
      CCL5 have established indicators for disease status in various cancers, including
      PC. However, their role in invasion and metastasis of PC is not known. Here we
      conducted immunohistochemistry of PC tissues and found elevated epithelial
      staining for CCR5 and CCL5 in metastatic PC tissues compared to non-neoplastic.
      In vitro experiments, such as flow cytometry, immunofluorescence and western
      blotting with human PC cell lines (AsPc-1, BxPc-3 and MIA PaCa-2), showed higher
      expression levels of CCR5. The CCL5 activation of PC cells expressing CCR5
      increased their invasive potential, while treatment with CCR5 inhibitor maraviroc
      inhibited the CCL5 activation. CCL5 induced proliferation of PC cells was
      mediated through F-actin polymerization, while there was marked reduction when
      the cells were treated with maraviroc. The direct interaction of CCR5 with CCL5
      was verified using a calcium mobilization assay. Taken together, our results
      demonstrate that CCR5 and CCL5 are potential markers for metastatic PC cancer,
      and their interaction leads to the increased PC cell invasion. Thus, blocking
      CCR5/CCL5 axis might prove beneficial to prevent metastasis and provide a more
      therapeutic strategy to control PC progression.

PMID- 29358633
TI  - Sperm-borne phospholipase C zeta-1 ensures monospermic fertilization in mice.
AB  - Sperm entry in mammalian oocytes triggers intracellular Ca2+ oscillations that
      initiate resumption of the meiotic cell cycle and subsequent activations. Here,
      we show that phospholipase C zeta 1 (PLCzeta1) is the long-sought sperm-borne
      oocyte activation factor (SOAF). Plcz1 gene knockout (KO) mouse spermatozoa fail
      to induce Ca2+ changes in intracytoplasmic sperm injection (ICSI). In contrast to
      ICSI, Plcz1 KO spermatozoa induced atypical patterns of Ca2+ changes in normal
      fertilizations, and most of the fertilized oocytes ceased development at the 1-2
      cell stage because of oocyte activation failure or polyspermy. We further
      discovered that both zona pellucida block to polyspermy (ZPBP) and plasma
      membrane block to polyspermy (PMBP) were delayed in oocytes fertilized with Plcz1
      KO spermatozoa. With the observation that polyspermy is rare in astacin-like
      metalloendopeptidase (Astl) KO female oocytes that lack ZPBP, we conclude that
      PMPB plays more critical role than ZPBP in vivo. Finally, we obtained healthy
      pups from male mice carrying human infertile PLCZ1 mutation by single sperm ICSI
      supplemented with Plcz1 mRNA injection. These results suggest that mammalian
      spermatozoa have a primitive oocyte activation mechanism and that PLCzeta1 is a
      SOAF that ensures oocyte activation steps for monospermic fertilization in
      mammals.

PMID- 29358634
TI  - Reversible 2D Supramolecular Organic Frameworks encompassing Viologen Cation
      Radicals and CB[8].
AB  - Reversible 2D supramolecular organic frameworks encompassing branched viologen
      architectures and cucurbit[8]uril (CB[8]) were constructed and investigated. UV
      vis investigation clearly indicates the formation and intermolecular dimerization
      of monocation radicals and their encapsulation into the hydrophobic CB[8] cavity
      which is further complemented by EPR (electron paramagnetic resonance)
      spectroscopy. Particle size measurements by dynamic light scattering method
      showed particle sizes in the range of several um indicating larger aggregates.
      Zeta potential measurements suggested the instability of these particles and
      their tendency to form aggregates. TEM (transmission electron microscope)
      analysis further revealed the formation of supramolecular polymer (monocation
      radical with cucurbit[8]uril) whose diameter were in the range of several um as
      indicated by DLS measurements; however the oxidized form, i.e., the viologen
      dication with cucurbit[8]uril showed dotted spots in the range of sub nanometer
      level. The internal periodicities of the supramolecular polymers were analyzed by
      SAXs (small angle X-ray scattering) measurements. Additionally, we have
      demonstrated that these supramolecular organic frameworks can be depolymerized by
      oxidation in air and again can be polymerized (intermolecular radical
      dimerization) by reduction under inert atmosphere demonstrating that these
      systems will be of broad interest.

PMID- 29358635
TI  - Lambda-enhanced grey molasses on the D2 transition of Rubidium-87 atoms.
AB  - Laser cooling based on dark states, i.e. states decoupled from light, has proven
      to be effective to increase the phase-space density of cold trapped atoms. Dark
      states cooling requires open atomic transitions, in contrast to the ordinary
      laser cooling used for example in magneto-optical traps (MOTs), which operate on
      closed atomic transitions. For alkali atoms, dark-states cooling is therefore
      commonly operated on the D1 transition nS1/2 -> nP1/2. We show that, for 87Rb,
      thanks to the large hyperfine structure separations the use of this transition is
      not strictly necessary and that "quasi-dark state" cooling is efficient also on
      the D2 line, 5S1/2 -> 5P3/2. We report temperatures as low as (4.0 +/- 0.3) MUK
      and an increase of almost an order of magnitude in the phase space density with
      respect to ordinary laser sub-Doppler cooling.

PMID- 29358638
TI  - Giant photoeffect in proton transport through graphene membranes.
AB  - Graphene has recently been shown to be permeable to thermal protons 1 , the
      nuclei of hydrogen atoms, which sparked interest in its use as a proton
      conducting membrane in relevant technologies1-4. However, the influence of light
      on proton permeation remains unknown. Here we report that proton transport
      through Pt-nanoparticle-decorated graphene can be enhanced strongly by
      illuminating it with visible light. Using electrical measurements and mass
      spectrometry, we find a photoresponsivity of ~104 A W-1, which translates into a
      gain of ~104 protons per photon with response times in the microsecond range.
      These characteristics are competitive with those of state-of-the-art
      photodetectors that are based on electron transport using silicon and novel two
      dimensional materials5-7. The photo-proton effect could be important for
      graphene's envisaged use in fuel cells and hydrogen isotope separation. Our
      observations may also be of interest for other applications such as light-induced
      water splitting, photocatalysis and novel photodetectors.

PMID- 29358636
TI  - Association between H-type Hypertension and Asymptomatic Extracranial Artery
      Stenosis.
AB  - Asymptomatic extracranial artery stenosis (ECAS) is a well-known risk factor for
      stroke and H-type hypertension, which is defined as hypertension with
      hyperhomocysteinemia, is associated with cardio-cerebrovascular diseases.
      However, the impact of H-type hypertension on ECAS is mostly unknown. We designed
      this study to investigate the association between H-type hypertension and
      prevalence of ECAS. We included 2330 participants in this study and classified
      them into four groups: the control group without hypertension or
      hyperhomocysteinemia, isolated hypertension group, isolated hyperhomocysteinemia
      group and H-type hypertension group. We measured the baseline plasma total
      homocysteine levels and assessed ECAS by carotid duplex sonography twice at
      baseline and during follow up. We used a Cox regression model to analyse the
      association between H-type hypertension and ECAS. At baseline, 608 subjects
      suffered from H-type hypertension. Within two years of follow-up, asymptomatic
      ECAS occurred in 250 (10.73%) participants. After adjusting for relevant risk
      factors, we found H-type hypertension to be an independent risk factor for
      asymptomatic ECAS (relative risk (RR) 3.16, 95% confidence interval (95% CI) 2.00
      5.00). Our findings provide direct evidence for the importance of H-type
      hypertension in the occurrence of ECAS and as a potential therapeutic target for
      carotid atherosclerosis.

PMID- 29358629
TI  - Telomerecat: A ploidy-agnostic method for estimating telomere length from whole
      genome sequencing data.
AB  - Telomere length is a risk factor in disease and the dynamics of telomere length
      are crucial to our understanding of cell replication and vitality. The
      proliferation of whole genome sequencing represents an unprecedented opportunity
      to glean new insights into telomere biology on a previously unimaginable scale.
      To this end, a number of approaches for estimating telomere length from whole
      genome sequencing data have been proposed. Here we present Telomerecat, a novel
      approach to the estimation of telomere length. Previous methods have been
      dependent on the number of telomeres present in a cell being known, which may be
      problematic when analysing aneuploid cancer data and non-human samples.
      Telomerecat is designed to be agnostic to the number of telomeres present, making
      it suited for the purpose of estimating telomere length in cancer studies.
      Telomerecat also accounts for interstitial telomeric reads and presents a novel
      approach to dealing with sequencing errors. We show that Telomerecat performs
      well at telomere length estimation when compared to leading experimental and
      computational methods. Furthermore, we show that it detects expected patterns in
      longitudinal data, repeated measurements, and cross-species comparisons. We also
      apply the method to a cancer cell data, uncovering an interesting relationship
      with the underlying telomerase genotype.

PMID- 29358639
TI  - Manipulation of domain-wall solitons in bi- and trilayer graphene.
AB  - Topological dislocations and stacking faults greatly affect the performance of
      functional crystalline materials1-3. Layer-stacking domain walls (DWs) in
      graphene alter its electronic properties and give rise to fascinating new physics
      such as quantum valley Hall edge states4-10. Extensive efforts have been
      dedicated to the engineering of dislocations to obtain materials with advanced
      properties. However, the manipulation of individual dislocations to precisely
      control the local structure and local properties of bulk material remains an
      outstanding challenge. Here we report the manipulation of individual layer
      stacking DWs in bi- and trilayer graphene by means of a local mechanical force
      exerted by an atomic force microscope tip. We demonstrate experimentally the
      capability to move, erase and split individual DWs as well as annihilate or
      create closed-loop DWs. We further show that the DW motion is highly anisotropic,
      offering a simple approach to create solitons with designed atomic structures.
      Most artificially created DW structures are found to be stable at room
      temperature.

PMID- 29358637
TI  - Precision of a new ocular biometer in children and comparison with IOLMaster.
AB  - To assess the repeatability and reproducibility of AL-Scan in agreement with
      those by the IOLMaster in healthy children, two skilled operators measured ocular
      parameters in 58 children. The parameters included keratometry (K) values,
      anterior chamber depth (ACD), axial length (AL), central corneal thickness (CCT),
      pupil diameter (PD), and corneal diameter (CD). The cohort comprised of 32 boys
      and 26 girls. The AL-Scan measurements showed high repeatability, as the test
      retest repeatability (TRT) values of AL, CCT, ACD, Kf, Ks, Km, CD, and PD were
      0.09 mm, 5.1 MUm, 0.04 mm, 0.28 D, 0.24 D, 0.21 D, 0.39 mm, and 0.22 mm,
      respectively. The within-subject coefficient of variation (CoV) was low (<0.35%)
      and the intraclass correlation coefficients (ICC) of all parameters were >0.85.
      The interobserver reproducibility was excellent with low values of TRT and ICC >
      0.95. The CoV of AL, CCT, ACD, and K was <0.22%. The 95% limits of agreement
      between the AL-Scan and the IOLMaster were narrow for all parameters except for
      CD. The repeatability and reproducibility of the new biometer, Al-Scan, was
      excellent for all parameters and can be routinely used in children to measure the
      biometric values.

PMID- 29358642
TI  - SiGe epitaxial memory for neuromorphic computing with reproducible high
      performance based on engineered dislocations.
AB  - Although several types of architecture combining memory cells and transistors
      have been used to demonstrate artificial synaptic arrays, they usually present
      limited scalability and high power consumption. Transistor-free analog switching
      devices may overcome these limitations, yet the typical switching process they
      rely on-formation of filaments in an amorphous medium-is not easily controlled
      and hence hampers the spatial and temporal reproducibility of the performance.
      Here, we demonstrate analog resistive switching devices that possess desired
      characteristics for neuromorphic computing networks with minimal performance
      variations using a single-crystalline SiGe layer epitaxially grown on Si as a
      switching medium. Such epitaxial random access memories utilize threading
      dislocations in SiGe to confine metal filaments in a defined, one-dimensional
      channel. This confinement results in drastically enhanced switching uniformity
      and long retention/high endurance with a high analog on/off ratio. Simulations
      using the MNIST handwritten recognition data set prove that epitaxial random
      access memories can operate with an online learning accuracy of 95.1%.

PMID- 29358643
TI  - From window to solar cell and back.

PMID- 29358641
TI  - An integrated multi-layer 3D-fabrication of PDA/RGD coated graphene loaded PCL
      nanoscaffold for peripheral nerve restoration.
AB  - As a conductive nanomaterial, graphene has huge potentials in nerve function
      restoration by promoting electrical signal transduction and metabolic activities
      with unique topological properties. Polydopamine (PDA) and arginylglycylaspartic
      acid (RGD) can improve cell adhesion in tissue engineering. Here we report an
      integrated 3D printing and layer-by-layer casting (LBLC) method in multi-layered
      porous scaffold fabrication. The scaffold is composed of single-layered graphene
      (SG) or multi-layered graphene (MG) and polycaprolactone (PCL). The electrically
      conductive 3D graphene scaffold can significantly improve neural expression both
      in vitro and in vivo. It promotes successful axonal regrowth and remyelination
      after peripheral nerve injury. These findings implicate that graphene-based
      nanotechnology have great potentials in peripheral nerve restoration in
      preclinical and clinical application.

PMID- 29358644
TI  - Tightening grip.

PMID- 29358640
TI  - New functions of Semaphorin 3E and its receptor PlexinD1 during developing and
      adult hippocampal formation.
AB  - The development and maturation of cortical circuits relies on the coordinated
      actions of long and short range axonal guidance cues. In this regard, the class 3
      semaphorins and their receptors have been seen to be involved in the development
      and maturation of the hippocampal connections. However, although the role of most
      of their family members have been described, very few data about the
      participation of Semaphorin 3E (Sema3E) and its receptor PlexinD1 during the
      development and maturation of the entorhino-hippocampal (EH) connection are
      available. In the present study, we focused on determining their roles both
      during development and in adulthood. We determined a relevant role for
      Sema3E/PlexinD1 in the layer-specific development of the EH connection. Indeed,
      mice lacking Sema3E/PlexinD1 signalling showed aberrant layering of entorhinal
      axons in the hippocampus during embryonic and perinatal stages. In addition,
      absence of Sema3E/PlexinD1 signalling results in further changes in postnatal and
      adult hippocampal formation, such as numerous misrouted ectopic mossy fibers.
      More relevantly, we describe how subgranular cells express PlexinD1 and how the
      absence of Sema3E induces a dysregulation of the proliferation of dentate gyrus
      progenitors leading to the presence of ectopic cells in the molecular layer.
      Lastly, Sema3E mutant mice displayed increased network excitability both in the
      dentate gyrus and the hippocampus proper.

PMID- 29358645
TI  - Thermochromic halide perovskite solar cells.
AB  - Smart photovoltaic windows represent a promising green technology featuring
      tunable transparency and electrical power generation under external stimuli to
      control the light transmission and manage the solar energy. Here, we demonstrate
      a thermochromic solar cell for smart photovoltaic window applications utilizing
      the structural phase transitions in inorganic halide perovskite caesium lead
      iodide/bromide. The solar cells undergo thermally-driven, moisture-mediated
      reversible transitions between a transparent non-perovskite phase (81.7% visible
      transparency) with low power output and a deeply coloured perovskite phase (35.4%
      visible transparency) with high power output. The inorganic perovskites exhibit
      tunable colours and transparencies, a peak device efficiency above 7%, and a
      phase transition temperature as low as 105  degrees C. We demonstrate excellent
      device stability over repeated phase transition cycles without colour fade or
      performance degradation. The photovoltaic windows showing both photoactivity and
      thermochromic features represent key stepping-stones for integration with
      buildings, automobiles, information displays, and potentially many other
      technologies.

PMID- 29358646
TI  - Role of helical edge modes in the chiral quantum anomalous Hall state.
AB  - Although indications are that a single chiral quantum anomalous Hall(QAH) edge
      mode might have been experimentally detected. There have been very many recent
      experiments which conjecture that a chiral QAH edge mode always materializes
      along with a pair of quasi-helical quantum spin Hall (QSH) edge modes. In this
      work we deal with a substantial 'What If?' question- in case the QSH edge modes,
      from which these QAH edge modes evolve, are not topologically-protected then the
      QAH edge modes wont be topologically-protected too and thus unfit for use in any
      applications. Further, as a corollary one can also ask if the topological
      protection of QSH edge modes does not carry over during the evolution process to
      QAH edge modes then again our 'What if?' scenario becomes apparent. The 'how' of
      the resolution of this 'What if?' conundrum is the main objective of our work. We
      show in similar set-ups affected by disorder and inelastic scattering, transport
      via trivial QAH edge mode leads to quantization of Hall resistance and not that
      via topological QAH edge modes. This perhaps begs a substantial reinterpretation
      of those experiments which purported to find signatures of chiral(topological)
      QAH edge modes albeit in conjunction with quasi helical QSH edge modes.

PMID- 29358647
TI  - Unanticipated functional diversity among the TatA-type components of the Tat
      protein translocase.
AB  - Twin-arginine translocation (Tat) systems transport folded proteins that harbor a
      conserved arginine pair in their signal peptides. They assemble from hexahelical
      TatC-type and single-spanning TatA-type proteins. Many Tat systems comprise two
      functionally diverse, TatA-type proteins, denominated TatA and TatB. Some
      bacteria in addition express TatE, which thus far has been characterized as a
      functional surrogate of TatA. For the Tat system of Escherichia coli we
      demonstrate here that different from TatA but rather like TatB, TatE contacts a
      Tat signal peptide independently of the proton-motive force and restricts the
      premature processing of a Tat signal peptide. Furthermore, TatE embarks at the
      transmembrane helix five of TatC where it becomes so closely spaced to TatB that
      both proteins can be covalently linked by a zero-space cross-linker. Our results
      suggest that in addition to TatB and TatC, TatE is a further component of the Tat
      substrate receptor complex. Consistent with TatE being an autonomous TatAB-type
      protein, a bioinformatics analysis revealed a relatively broad distribution of
      the tatE gene in bacterial phyla and highlighted unique protein sequence features
      of TatE orthologs.

PMID- 29358648
TI  - Four-week individual caging of male ICR mice alters body composition without
      change in body mass.
AB  - Understanding the physiological implications of caging conditions for mice is
      crucial in improving the replicability and reliability of animal research.
      Individual caging of mice is known to alter mouse psychology, such as triggering
      depression-like symptoms in mice, suggesting that caging conditions could have
      negative effects on mice. Therefore, we hypothesized that individual caging could
      affect the physical composition of outbred mice. To investigate this, dual X-ray
      absorptiometry (DXA) was used to compare the mass, bone mineral content (BMC),
      bone mineral density (BMD), lean tissue percentage and fat tissue percentage
      between group and individual caged mice. We also conducted open field test to
      compare mouse activities in different caging conditions. Our results showed
      significantly reduced BMD and lean tissue percentage and significantly increased
      fat tissue percentage in individually-caged male mice. Furthermore, there were no
      differences in body mass and activity between the grouped and individual mice,
      suggesting that these physical alterations were not induced by group-related
      activity. In this study, we conclude that individual caging could alter the body
      composition of mice without affecting external morphology.

PMID- 29358650
TI  - Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of
      cell fate.
AB  - Pioneer transcription factors establish new cell-fate competence by triggering
      chromatin remodeling. However, many features of pioneer action, such as their
      kinetics and stability, remain poorly defined. Here, we show that Pax7, by
      opening a unique repertoire of enhancers, is necessary and sufficient for
      specification of one pituitary lineage. Pax7 binds its targeted enhancers
      rapidly, but chromatin remodeling and gene activation are slower. Enhancers
      opened by Pax7 show a loss of DNA methylation and acquire stable epigenetic
      memory, as evidenced by binding of nonpioneer factors after Pax7 withdrawal. This
      work shows that transient Pax7 expression is sufficient for stable specification
      of cell identity.

PMID- 29358649
TI  - Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium
      tuberculosis.
AB  - To characterize the genetic determinants of resistance to antituberculosis drugs,
      we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium
      tuberculosis clinical isolates from more than 30 countries. A GWAS approach
      within a mixed-regression framework was followed by a phylogenetics-based test
      for independent mutations. In addition to mutations in established and recently
      described resistance-associated genes, novel mutations were discovered for
      resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity
      to detect mutations associated with resistance to ethionamide, pyrazinamide,
      capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion
      of insertions and deletions. Odds ratios for mutations within candidate genes
      were found to reflect levels of resistance. New epistatic relationships between
      candidate drug-resistance-associated genes were identified. Findings also suggest
      the involvement of efflux pumps (drrA and Rv2688c) in the emergence of
      resistance. This study will inform the design of new diagnostic tests and
      expedite the investigation of resistance and compensatory epistatic mechanisms.

PMID- 29358651
TI  - Genomes of 13 domesticated and wild rice relatives highlight genetic
      conservation, turnover and innovation across the genus Oryza.
AB  - The genus Oryza is a model system for the study of molecular evolution over time
      scales ranging from a few thousand to 15 million years. Using 13 reference
      genomes spanning the Oryza species tree, we show that despite few large-scale
      chromosomal rearrangements rapid species diversification is mirrored by lineage
      specific emergence and turnover of many novel elements, including transposons,
      and potential new coding and noncoding genes. Our study resolves controversial
      areas of the Oryza phylogeny, showing a complex history of introgression among
      different chromosomes in the young 'AA' subclade containing the two domesticated
      species. This study highlights the prevalence of functionally coupled disease
      resistance genes and identifies many new haplotypes of potential use for future
      crop protection. Finally, this study marks a milestone in modern rice research
      with the release of a complete long-read assembly of IR 8 'Miracle Rice', which
      relieved famine and drove the Green Revolution in Asia 50 years ago.

PMID- 29358653
TI  - Bph6 encodes an exocyst-localized protein and confers broad resistance to
      planthoppers in rice.
AB  - The brown planthopper (BPH) and white-backed planthopper (WBPH) are the most
      destructive insect pests of rice, and they pose serious threats to rice
      production throughout Asia. Thus, there are urgent needs to identify resistance
      conferring genes and to breed planthopper-resistant rice varieties. Here we
      report the map-based cloning and functional analysis of Bph6, a gene that confers
      resistance to planthoppers in rice. Bph6 encodes a previously uncharacterized
      protein that localizes to exocysts and interacts with the exocyst subunit
      OsEXO70E1. Bph6 expression increases exocytosis and participates in cell wall
      maintenance and reinforcement. A coordinated cytokinin, salicylic acid and
      jasmonic acid signaling pathway is activated in Bph6-carrying plants, which
      display broad resistance to all tested BPH biotypes and to WBPH without
      sacrificing yield, as these plants were found to maintain a high level of
      performance in a field that was heavily infested with BPH. Our results suggest
      that a superior resistance gene that evolved long ago in a region where
      planthoppers are found year round could be very valuable for controlling
      agricultural insect pests.

PMID- 29358654
TI  - Genetic determinants and epigenetic effects of pioneer-factor occupancy.
AB  - Transcription factors (TFs) direct developmental transitions by binding to target
      DNA sequences, influencing gene expression and establishing complex gene
      regultory networks. To systematically determine the molecular components that
      enable or constrain TF activity, we investigated the genomic occupancy of FOXA2,
      GATA4 and OCT4 in several cell types. Despite their classification as pioneer
      factors, all three TFs exhibit cell-type-specific binding, even when
      supraphysiologically and ectopically expressed. However, FOXA2 and GATA4 can be
      distinguished by low enrichment at loci that are highly occupied by these factors
      in alternative cell types. We find that expression of additional cofactors
      increases enrichment at a subset of these sites. Finally, FOXA2 occupancy and
      changes to DNA accessibility can occur in G1-arrested cells, but subsequent loss
      of DNA methylation requires DNA replication.

PMID- 29358652
TI  - The sea lamprey germline genome provides insights into programmed genome
      rearrangement and vertebrate evolution.
AB  - The sea lamprey (Petromyzon marinus) serves as a comparative model for
      reconstructing vertebrate evolution. To enable more informed analyses, we
      developed a new assembly of the lamprey germline genome that integrates several
      complementary data sets. Analysis of this highly contiguous (chromosome-scale)
      assembly shows that both chromosomal and whole-genome duplications have played
      significant roles in the evolution of ancestral vertebrate and lamprey genomes,
      including chromosomes that carry the six lamprey HOX clusters. The assembly also
      contains several hundred genes that are reproducibly eliminated from somatic
      cells during early development in lamprey. Comparative analyses show that
      gnathostome (mouse) homologs of these genes are frequently marked by polycomb
      repressive complexes (PRCs) in embryonic stem cells, suggesting overlaps in the
      regulatory logic of somatic DNA elimination and bivalent states that are
      regulated by early embryonic PRCs. This new assembly will enhance diverse studies
      that are informed by lampreys' unique biology and evolutionary/comparative
      perspective.

PMID- 29358655
TI  - PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating
      IFIT2.
AB  - Gallbladder cancer (GBC) is a malignant cancer with very poor prognosis. Although
      promyelocytic leukemia zinc-finger protein (PLZF) was reported to be deregulated
      in numerous cancers and also relevant to clinical prognosis, its role in GBC
      progression has been little known. In this study, we found PLZF expression was
      decreased in GBC, correlating to advanced TNM stage, distant metastasis, and
      shorter overall survival. Moreover, ectopic PLZF expression in GBC cells (NOZ and
      GBC-SD) significantly reduced the cell proliferation, migration, and invasion.
      Consistently, overexpression of PLZF in xenograft mice model could suppress tumor
      growth and liver metastasis. Mechanical investigations verified PLZF could
      regulate the expression of cell cycle arrest-associated gene p21 and epithelial
      mesenchymal transition (EMT)-related genes (E-cadherin and N-cadherin) in GBC
      cell lines. Importantly, PLZF remarkably increased the mRNA transcription of
      interferon-induced protein with tetratricopeptide repeat 2 (IFIT2) by increasing
      STAT1 protein level, a known factor involved in tumor progression. Furthermore,
      ablation of IFIT2 in PLZF overexpression cells abrogated the tumor-suppressive
      function of PLZF, at least partially, leading to impaired tumor growth and EMT
      program. These studies indicated PLZF inhibited the proliferation and metastasis
      via regulation of IFIT2. In conclusion, our study demonstrated PLZF could be a
      promising tumor biomarker for GBC, and also be a potential therapeutic target.

PMID- 29358656
TI  - Functional genomics study of acute heat stress response in the small yellow
      follicles of layer-type chickens.
AB  - This study investigated global gene and protein expression in the small yellow
      follicle (SYF; 6-8 mm in diameter) tissues of chickens in response to acute heat
      stress. Twelve 30-week-old layer-type hens were divided into four groups: control
      hens were maintained at 25  degrees C while treatment hens were subjected to
      acute heat stress at 36  degrees C for 4 h without recovery, with 2-h recovery,
      and with 6-h recovery. SYFs were collected at each time point for mRNA and
      protein analyses. A total of 176 genes and 93 distinct proteins with differential
      expressions were identified, mainly associated with the molecular functions of
      catalytic activity and binding. The upregulated expression of heat shock proteins
      and peroxiredoxin family after acute heat stress is suggestive of responsive
      machineries to protect cells from apoptosis and oxidative insults. In conclusion,
      both the transcripts and proteins associated with apoptosis, stress response, and
      antioxidative defense were upregulated in the SYFs of layer-type hens to
      alleviate the detrimental effects by acute heat stress. However, the genomic
      regulations of specific cell type in response to acute heat stress of SYFs
      require further investigation.

PMID- 29358657
TI  - Interaction between hippocampal-prefrontal plasticity and thalamic-prefrontal
      activity.
AB  - The prefrontal cortex integrates a variety of cognition-related inputs, either
      unidirectional, e.g., from the hippocampal formation, or bidirectional, e.g.,
      with the limbic thalamus. While the former is usually implicated in synaptic
      plasticity, the latter is better known for regulating ongoing activity.
      Interactions between these processes via prefrontal neurons are possibly
      important for linking mnemonic and executive functions. Our work further
      elucidates such dynamics using in vivo electrophysiology in rats. First, we
      report that electrical pulses into CA1/subiculum trigger late-onset (>400 ms)
      firing responses in the medial prefrontal cortex, which are increased after
      induction of long-term potentiation. Then, we show these responses to be
      attenuated by optogenetic control of the paraventricular/mediodorsal thalamic
      area. This suggests that recruitment and plasticity of the hippocampal-prefrontal
      pathway is partially related to the thalamic-prefrontal loop. When dysfunctional,
      this interaction may contribute to cognitive deficits, psychotic symptoms, and
      seizure generalization, which should motivate future studies combining
      behavioural paradigms and long-range circuit assessment.

PMID- 29358658
TI  - Establishment of an easy and straight forward heparinase protocol to analyse
      circulating and myocardial tissue micro-RNA during coronary artery-bypass-graft
      surgery.
AB  - Coronary artery-bypass-graft (CABG) surgery is associated with myocardial damage
      and increased blood concentrations of circulating microRNAs (miRNA). However,
      whether and to what extent these miRNAs relate to cardiac tissue miRNA expression
      have not yet been explored. Since plasma miRNA quantification in samples from
      cardiopulmonary bypass (CPB) patients is severely hampered by heparin, we
      established and validated successfully a protocol to reliably measure miRNA in 49
      heparinized patients undergoing CABG so as to investigate the relationship
      between circulating and right atrial miRNAs. Plasma and right atrial expression
      of miR-1, miR-133a, miR-423-5p, and miR-499 were measured before and after CPB,
      as well as miRNAs in plasma 24 h thereafter. All plasma miRNAs increased
      significantly with surgery while cardiac tissue expression of only miR-133a (1.4
      fold; p = 0.003) and miR-423-5p (1.3 fold; p = 0.025) increased as well. Right
      atrial and plasma miR-133a expression correlated positively before CPB (r =
      0.288, p = 0.045) but miR-499 expression inversely (r = -0.484, p = 0.0004).
      There was a strong association between plasma miR-133a and miR-499 concentrations
      and postoperative troponin I concentrations, the marker for myocardial damage.
      Increased myocardial miR-133a and miR-423-5p expression together with unchanged
      miR-1 and miR-499 expression might suggest active release of these miRNAs rather
      than their origin from damaged cells.

PMID- 29358659
TI  - Orientation of non-spherical protonated water clusters revealed by infrared
      absorption dichroism.
AB  - Infrared continuum bands that extend over a broad frequency range are a key
      spectral signature of protonated water clusters. They are observed for many
      membrane proteins that contain internal water molecules, but their microscopic
      mechanism has remained unclear. Here we compute infrared spectra for protonated
      and unprotonated water chains, discs, and droplets from ab initio molecular
      dynamics simulations. The continuum bands of the protonated clusters exhibit
      significant anisotropy for chains and discs, with increased absorption along the
      direction of maximal cluster extension. We show that the continuum band arises
      from the nuclei motion near the excess charge, with a long-ranged amplification
      due to the electronic polarizability. Our experimental, polarization-resolved
      light-dark difference spectrum of the light-driven proton pump bacteriorhodopsin
      exhibits a pronounced dichroic continuum band. Our results suggest that the
      protonated water cluster responsible for the continuum band of bacteriorhodopsin
      is oriented perpendicularly to the membrane normal.

PMID- 29358660
TI  - Tuning bandgap and surface wettability of NiFe2O4 driven by phase transition.
AB  - Stress variation induced bandgap tuning and surface wettability switching of
      spinel nickel ferrite (NiFe2O4, NFO) films were demonstrated and directly driven
      by phase transition via a post-annealing process. Firstly, the as-deposited NFO
      films showed hydrophilic surface with water contact angle (CA) value of 80 +/- 1
      degrees . After post-annealing with designed temperatures ranged from 400 to 700 
      degrees C in air ambience for 1 hour, we observed that the crystal structure was
      clearly improved from amorphous-like/ nanocrystalline to polycrystalline with
      increasing post-annealing temperature and this phenomenon is attributed to the
      improved crystallinity combined with relaxation of internal stress. Moreover,
      super-hydrophilic surface (CA = 14 +/- 1 degrees ) was occurred due to the
      remarkable grain structure transition. The surface wettability could be adjusted
      from hydrophilicity to super-hydrophilicity by controlling grain morphology of
      NFO films. Simultaneously, the saturation magnetization (Ms) values of NFO films
      at room temperature increased up to 273 emu/cm3 accompanied with transitions of
      the phase and grain structure. We also observed an exceptionally tunable bandgap
      of NFO in the range between 1.78 and 2.72 eV under phase transition driving.
      Meanwhile, our work demonstrates that direct grain morphology combined with the
      stress tuning can strongly modulate the optical, surface and magnetic
      characteristics in multifunctional NFO films.

PMID- 29358661
TI  - Anthelmintic niclosamide suppresses transcription of BCR-ABL fusion oncogene via
      disabling Sp1 and induces apoptosis in imatinib-resistant CML cells harboring
      T315I mutant.
AB  - Tyrosine kinase BCR-ABL fusion protein is the driver in patients with chronic
      myeloid leukemia (CML). The gate-keeper mutation T315I is the most challenging
      mutant due to its resistance to most tyrosine kinase inhibitors (TKIs). The third
      generation TKI ponatinib is the only effective TKI to treat CML patients
      harboring T315I-BCR-ABL mutation, but with high rate of major arterial thrombotic
      events. Alternative strategies to specifically target T315I-BCR-ABL are needed
      for the treatment of CML patients harboring such a mutation. Given that Sp1 is a
      fundamental transcriptional factor to positively regulate WT-BCR-ABL fusion
      oncogene, the purpose of this investigation was aimed at evaluating the anti
      tumor activity and the underlying mechanism in terms of Sp1 regulational effect
      on the transcription of T315I-BCR-ABL fusion oncogene. Like in WT-BCR-ABL, we
      identified enrichment of Sp1 on the promoter of T315I-BCR-ABL fusion gene.
      Treatment of WT- and T315I-BCR-ABL-expressing CML cells by niclosamide diminished
      such an enrichment of Sp1, and decreased WT- and T315I-BCR-ABL transcription and
      its downstream signaling molecules such as STAT5 and Akt. Further, niclosamide
      significantly inhibited the proliferation and induced apoptosis through intrinsic
      pathway. The in vivo efficacy validation of p-niclosamide, a water soluble
      derivative of niclosamide, showed that p-niclosamide significantly inhibited the
      tumor burden of nude mice subcutaneously bearing T315I-BCR-ABL-expressing CML
      cells, and prolonged the survival of allografted leukemic mice harboring BaF3
      T315I-BCR-ABL. We conclude that niclosamide is active against T315I-BCR-ABL
      expressing cells, and may be a promising agent for CML patients regardless of
      T315I mutation status.

PMID- 29358662
TI  - Network of proteins, enzymes and genes linked to biomass degradation shared by
      Trichoderma species.
AB  - Understanding relationships between genes responsible for enzymatic hydrolysis of
      cellulose and synergistic reactions is fundamental for improving biomass
      biodegradation technologies. To reveal synergistic reactions, the transcriptome,
      exoproteome, and enzymatic activities of extracts from Trichoderma harzianum,
      Trichoderma reesei and Trichoderma atroviride under biodegradation conditions
      were examined. This work revealed co-regulatory networks across carbohydrate
      active enzyme (CAZy) genes and secreted proteins in extracts. A set of 80
      proteins and respective genes that might correspond to a common system for
      biodegradation from the studied species were evaluated to elucidate new co
      regulated genes. Differences such as one unique base pair between fungal genomes
      might influence enzyme-substrate binding sites and alter fungal gene expression
      responses, explaining the enzymatic activities specific to each species observed
      in the corresponding extracts. These differences are also responsible for the
      different architectures observed in the co-expression networks.

PMID- 29358663
TI  - Single crystal elasticity of natural topaz at high-temperatures.
AB  - Topaz is an aluminosilicate mineral phase stable in the hydrothermally altered
      pegmatitic rocks and also in subducted sedimentary lithologies. In nature, topaz
      often exhibits solid solution between fluorine and hydrous end members. We
      investigated elasticity of naturally occurring single crystal topaz
      (Al2SiO4F1.42(OH)0.58) using Resonant Ultrasound Spectroscopy. We also explored
      the temperature dependence of the full elastic constant tensor. We find that
      among the various minerals stable in the Al2O3-SiO2-H2O ternary system, topaz
      exhibits moderate elastic anisotropy. As a function of temperature, the sound
      velocity of topaz decreases with [Formula: see text] and [Formula: see text]
      being -3.10 and -2.30 * 10-4 km/s/K. The elasticity and sound velocity of topaz
      also vary as a function of OH and F content. The effect of composition ([Formula:
      see text]) on the velocity is equally important as that of the effect of
      temperature. We also note that the Debye temperature ([Formula: see text]) of
      topaz at room temperature condition is 910 K and decreases at higher temperature.
      The Debye temperature shows positive correlation with density of the mineral
      phases in the Al2O3-SiO2-H2O ternary system.

PMID- 29358664
TI  - Delayed onset of autoreactive antibody production and M2-skewed macrophages
      contribute to improved survival of TACI deficient MRL-Fas/Lpr mouse.
AB  - Anti-B cell activating factor belonging to TNF-family (BAFF) antibody therapy is
      indicated for the treatment of patients with active systemic lupus erythematosus
      (SLE). We hypothesized that the BAFF receptor, transmembrane activator and
      calcium-modulator and cyclophilin interactor (TACI) may be responsible for the
      generation of antibody secreting plasma cells in SLE. To test this hypothesis, we
      generated TACI deficient MRL-Fas/Lpr (LPR-TACI-/-) mouse. TACI deficiency
      resulted in improved survival of MRL-Fas/Lpr mice and delayed production of anti
      dsDNA and anti-SAM/RNP antibodies. There was also a delay in the onset of
      proteinuria and the accumulation of IgG and inflammatory macrophages (Mphis) in
      the glomeruli of young LPR-TACI-/- mice compared to wild-type mice. Underscoring
      the role of TACI in influencing Mphi phenotype, the transfer of Mphis from 12
      week-old LPR-TACI-/- mice to age-matched sick wild-type animals led to a decrease
      in proteinuria and improvement in kidney pathology. The fact that, in LPR-TACI-/-
      mouse a more pronounced delay was in IgM and IgG3 autoreactive antibody isotypes
      and the kinetics of follicular helper T (Tfh) cell-development was comparable
      between the littermates suggest a role for TACI in T cell-independent
      autoantibody production in MRL-Fas/Lpr mouse prior to the onset of T cell
      dependent antibody production.

PMID- 29358665
TI  - Anaerobic methanotrophic communities thrive in deep submarine permafrost.
AB  - Thawing submarine permafrost is a source of methane to the subsurface biosphere.
      Methane oxidation in submarine permafrost sediments has been proposed, but the
      responsible microorganisms remain uncharacterized. We analyzed archaeal
      communities and identified distinct anaerobic methanotrophic assemblages of
      marine and terrestrial origin (ANME-2a/b, ANME-2d) both in frozen and completely
      thawed submarine permafrost sediments. Besides archaea potentially involved in
      anaerobic oxidation of methane (AOM) we found a large diversity of archaea mainly
      belonging to Bathyarchaeota, Thaumarchaeota, and Euryarchaeota. Methane
      concentrations and delta13C-methane signatures distinguish horizons of potential
      AOM coupled either to sulfate reduction in a sulfate-methane transition zone
      (SMTZ) or to the reduction of other electron acceptors, such as iron, manganese
      or nitrate. Analysis of functional marker genes (mcrA) and fluorescence in situ
      hybridization (FISH) corroborate potential activity of AOM communities in
      submarine permafrost sediments at low temperatures. Modeled potential AOM
      consumes 72-100% of submarine permafrost methane and up to 1.2 Tg of carbon per
      year for the total expected area of submarine permafrost. This is comparable with
      AOM habitats such as cold seeps. We thus propose that AOM is active where
      submarine permafrost thaws, which should be included in global methane budgets.

PMID- 29358666
TI  - Inhibitory circuit gating of auditory critical-period plasticity.
AB  - Cortical sensory maps are remodeled during early life to adapt to the surrounding
      environment. Both sensory and contextual signals are important for induction of
      this plasticity, but how these signals converge to sculpt developing
      thalamocortical circuits remains largely unknown. Here we show that layer 1 (L1)
      of primary auditory cortex (A1) is a key hub where neuromodulatory and
      topographically organized thalamic inputs meet to tune the cortical layers below.
      Inhibitory interneurons in L1 send narrowly descending projections to
      differentially modulate thalamic drive to pyramidal and parvalbumin-expressing
      (PV) cells in L4, creating brief windows of intracolumnar activation. Silencing
      of L1 (but not VIP-expressing) cells abolishes map plasticity during the
      tonotopic critical period. Developmental transitions in nicotinic acetylcholine
      receptor (nAChR) sensitivity in these cells caused by Lynx1 protein can be
      overridden to extend critical-period closure. Notably, thalamocortical maps in L1
      are themselves stable, and serve as a scaffold for cortical plasticity throughout
      life.

PMID- 29358667
TI  - Rbm24, a target of p53, is necessary for proper expression of p53 and heart
      development.
AB  - Activation of p53-dependent apoptosis is critical for tumor suppression but
      aberrant activation of p53 also leads to developmental defects and heart failure.
      Here, we found that Rbm24 RNA-binding protein, a target of p53, regulates p53
      mRNA translation. Mechanistically, we found that through binding to p53 mRNA and
      interaction with translation initiation factor eIF4E, Rbm24 prevents eIF4E from
      binding to p53 mRNA and inhibits the assembly of translation initiation complex.
      Importantly, we showed that mice deficient in Rbm24 die in utero due to the
      endocardial cushion defect in the heart at least in part due to aberrant
      activation of p53-dependent apoptosis. We also showed that the heart
      developmental defect in Rbm24-null mice can be partially rescued by p53
      deficiency through decreased apoptosis in the heart. Together, we postulate that
      the p53-Rbm24 loop is critical for the heart development and may be explored for
      mitigating congenital heart diseases and heart failure.

PMID- 29358668
TI  - eIF2alpha phosphorylation is pathognomonic for immunogenic cell death.
AB  - The phosphorylation of eIF2alpha is essential for the endoplasmic reticulum (ER)
      stress response, the formation of stress granules, as well as macroautophagy.
      Several successful anticancer chemotherapeutics have the property to induce
      immunogenic cell death (ICD), thereby causing anticancer immune responses. ICD is
      accompanied by the translocation of calreticulin (CALR) from the ER lumen to the
      plasma membrane, which facilitates the transfer of tumor-associated antigens to
      dendritic cells. Here we systematically investigated the capacity of anticancer
      chemotherapeutics to induce signs of ER stress. ICD inducers including
      anthracyclines and agents that provoke tetraploidization were highly efficient in
      enhancing the phosphorylation of eIF2alpha, yet failed to stimulate other signs
      of ER stress including the transcriptional activation of activating transcription
      factor 4 (ATF4), the alternative splicing of X-box binding protein 1 (XBP1s) mRNA
      and the proteolytic cleavage of activating transcription factor 6 (ATF6) both in
      vitro and in cancers established in mice. Systematic analyses of clinically used
      anticancer chemotherapeutics revealed that only eIF2alpha phosphorylation, but
      none of the other signs of ER stress, correlated with CALR exposure. eIF2alpha
      phosphorylation induced by mitoxantrone, a prototype ICD-inducing anthracyline,
      was mediated by eIF2alpha kinase-3 (EIF2AK3). Machine-learning approaches were
      used to determine the physicochemical properties of drugs that induce ICD,
      revealing that the sole ER stress response relevant to the algorithm is eIF2alpha
      phosphorylation with its downstream consequences CALR exposure, stress granule
      formation and autophagy induction. Importantly, this approach could reduce the
      complexity of compound libraries to identify ICD inducers based on their
      physicochemical and structural characteristics. In summary, it appears that
      eIF2alpha phosphorylation constitutes a pathognomonic characteristic of ICD.

PMID- 29358669
TI  - BRAP-2 promotes DNA damage induced germline apoptosis in C. elegans through the
      regulation of SKN-1 and AKT-1.
AB  - As part of the DNA damage response (DDR) network, the tumour suppressor Breast
      cancer susceptibility gene 1 (BRCA1) is activated to facilitate DNA repair,
      transcription and cell cycle control. BRC-1, the Caenorhabditis elegans ortholog
      of BRCA1, has conserved function in DNA double strand break repair, wherein a
      loss of brc-1 results in high levels of germline apoptosis. BRAP2/IMP was
      initially identified as a BRCA1 associated binding protein and previously we have
      shown that the C. elegans brap-2 deletion mutant experiences BRC-1 dependent
      larval arrest when exposed to low concentrations of paraquat. Since BRC-1
      function in the germline is conserved, we wanted to determine the role of BRAP-2
      in DNA damage induced germline apoptosis in C. elegans. We examined levels of
      germ cell death following DNA damage and found that brap-2(ok1492) mutants
      display reduced levels of germline apoptosis when compared to the wild type, and
      the loss of brap-2 significantly reduced germ cell death in brc-1 mutant animals.
      We also found increased mRNA levels of skn-1 following DNA damage in brap-2
      mutants and that skn-1 RNAi knockdown in brap-2;brc-1 double mutants and a loss
      of pmk-1 mutation in brap-2 mutants increased apoptosis to wild type levels,
      indicating that brap-2 promotion of cell survival requires PMK-1 and SKN-1. Since
      mammalian BRAP2 has been shown to bind the AKT phosphatase PHLPP1/2, it suggests
      that BRAP2 could be involved in the Insulin/Insulin-like growth factor Signaling
      (IIS) pathway. We found that this interaction is conserved between the C. elegans
      homologs and that a loss of akt-1 in brap-2 mutants increased germline apoptosis.
      Thus in response to DNA damage, our findings suggest that BRAP-2 is required to
      attenuate the pro-cell survival signals of AKT-1 and PMK-1/SKN-1 to promote DNA
      damage induced germline apoptosis.

PMID- 29358670
TI  - TLR3 Mediates Repair and Regeneration of Damaged Neonatal Heart through
      Glycolysis Dependent YAP1 Regulated miR-152 Expression.
AB  - The present study investigated whether TLR3 is required for neonatal heart repair
      and regeneration following myocardial infarction (MI). TLR3 deficient neonatal
      mice exhibited impaired cardiac functional recovery and a larger infarct size,
      while wild type neonatal mice showed cardiac functional recovery and small
      infarct size after MI. The data suggest that TLR3 is essential for the
      regeneration and repair of damaged neonatal myocardium. In vitro treatment of
      neonatal cardiomyocytes with a TLR3 ligand, Poly (I:C), significantly enhances
      glycolytic metabolism, YAP1 activation and proliferation of cardiomyocytes which
      were prevented by a glycolysis inhibitor, 2-deoxyglucose (2-DG). Administration
      of 2-DG to neonatal mice abolished cardiac functional recovery and YAP activation
      after MI, suggesting that TLR3-mediated regeneration and repair of the damaged
      neonatal myocardium is through glycolytic-dependent YAP1 activation. Inhibition
      of YAP1 activation abolished Poly (I:C) induced proliferation of neonatal
      cardiomyocytes. Interestingly, activation of YAP1 increases the expression of miR
      152 which represses the expression of cell cycle inhibitory proteins, P27kip1 and
      DNMT1, leading to cardiomyocyte proliferation. We conclude that TLR3 is required
      for neonatal heart regeneration and repair after MI. The mechanisms involve
      glycolytic-dependent YAP1 activation, resulting in miR-152 expression which
      targets DNMT1/p27kip1.

PMID- 29358672
TI  - Large room-temperature tunneling anisotropic magnetoresistance and
      electroresistance in single ferromagnet/Nb:SrTiO3 Schottky devices.
AB  - There is a large effort in research and development to realize electronic devices
      capable of storing information in new ways - for instance devices which
      simultaneously exhibit electro and magnetoresistance. However it remains a
      challenge to create devices in which both effects coexist. In this work we show
      that the well-known electroresistance in noble metal-Nb:SrTiO3 Schottky junctions
      can be augmented by a magnetoresistance effect in the same junction. This is
      realized by replacing the noble metal electrode with ferromagnetic Co. This
      magnetoresistance manifests as a room temperature tunneling anisotropic
      magnetoresistance (TAMR). The maximum room temperature TAMR (1.6%) is
      significantly larger and robuster with bias than observed earlier, not using
      Nb:SrTiO3. In a different set of devices, a thin amorphous AlOx interlayer
      inserted between Co and Nb:SrTiO3, reduces the TAMR by more than 2 orders of
      magnitude. This points to the importance of intimate contact between the Co and
      Nb:SrTiO3 for the TAMR effect. This is explained by electric field enhanced spin
      orbit coupling of the interfacial Co layer in contact with Nb:SrTiO3. We propose
      that the large TAMR likely has its origin in the 3d orbital derived conduction
      band and large relative permittivity of Nb:SrTiO3 and discuss ways to further
      enhance the TAMR.

PMID- 29358671
TI  - TSC1 regulates osteoclast podosome organization and bone resorption through
      mTORC1 and Rac1/Cdc42.
AB  - Reorganization of the podosome into the sealing zone is crucial for osteoclasts
      (OCLs) to resorb bone, but the underlying mechanisms are unclear. Here, we show
      that tuberous sclerosis complex 1 (TSC1) functions centrally in OCLs to promote
      podosome organization and bone resorption through mechanistic target of rapamycin
      complex 1 (mTORC1) and the small GTPases Rac1/Cdc42. During osteoclastogenesis,
      enhanced expression of TSC1 downregulates mTORC1 activity. TSC1 deletion in OCLs
      reduced podosome belt formation in vitro and sealing zone formation in vivo,
      leading to bone resorption deficiency and osteopetrosis. Mechanistically, TSC1
      promoted podosome superstructure assembly by releasing mTORC1-dependent negative
      feedback inhibition of Rac1/Cdc42. Rapamycin and active Rac1/Cdc42 restore
      podosome organization and bone resorption and alleviate osteopetrotic phenotypes
      in mutant mice. Our findings reveal an essential role of TSC1 signaling in the
      regulation of bone resorption. Targeting TSC1 represents a novel strategy to
      inhibit bone resorption and prevent bone loss-related diseases.

PMID- 29358674
TI  - Electrical stimulation-a mapping system for hand dysfunction in tetraplegia.
AB  - STUDY DESIGN: Retrospective data analysis OBJECTIVES: To define the distribution
      of the motor points and excitability of the key wrist and finger actuators in
      order to detect upper (UMN) and lower motor neuron (LMN) lesions potentially
      influencing the development of a tenodesis grasp. SETTING: A rehabilitation
      centre for spinal cord injuries, Nottwil, Switzerland. METHODS: Forearm muscles
      of 32 patients with tetraplegia (AIS A-D) were tested bilaterally with electrical
      stimulation (ES) to differentiate whether UMN or LMN was present. For testing, a
      standardised mapping was developed. All patients underwent the same positioning
      schedule. RESULTS: Sixteen hands developed a tenodesis grasps, 24 hands showed
      neither shortening nor tightening of the finger flexors. Two patients developed
      unilateral tenodesis grasp and showed no tightening of the finger flexors on the
      contralateral hand. Seven patients developed tenodesis grasps symmetrically and
      bilaterally, whereas one maintained an essentially open hand without tightening
      of the finger flexors. All hands that developed a tenodesis grasp showed a LMN
      lesion of the M. extensor digitorum communis (EDC). The frequency of the
      tenodesis grasp differed significantly between the groups with and without intact
      reflex arc (p < 0.0001). CONCLUSION: Surface ES may serve as a diagnostic tool to
      detect an UMN or LMN lesion of the key actuator muscles affecting the tenodesis
      grasp. These findings provide information that is essential for the choice of
      treatment to optimise function of the tetraplegic hand.

PMID- 29358673
TI  - Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production
      supports colorectal cancer chemoresistance.
AB  - Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer.
      However, the significance of LD accumulation in colorectal cancer (CRC) biology
      is incompletely understood under chemotherapeutic conditions. Since drug
      resistance is a major obstacle to treatment success, we sought to determine the
      contribution of LD accumulation to chemotherapy resistance in CRC. Here we show
      that LD content of CRC cells positively correlates with the expression of
      lysophosphatidylcholine acyltransferase 2 (LPCAT2), an LD-localised enzyme
      supporting phosphatidylcholine synthesis. We also demonstrate that LD
      accumulation drives cell-death resistance to 5-fluorouracil and oxaliplatin
      treatments both in vitro and in vivo. Mechanistically, LD accumulation impairs
      caspase cascade activation and ER stress responses. Notably, droplet accumulation
      is associated with a reduction in immunogenic cell death and CD8+ T cell
      infiltration in mouse tumour grafts and metastatic tumours of CRC patients.
      Collectively our findings highlight LPCAT2-mediated LD accumulation as a
      druggable mechanism to restore CRC cell sensitivity.

PMID- 29358675
TI  - Early lexical processing of Chinese words indexed by Visual Mismatch Negativity
      effects.
AB  - Although Mismatch Negativity (MMN) effects indicating early, automatic lexical
      processing have been reported in the auditory language modality, so far these
      have not been reliably obtained in MMN studies of visual word recognition. The
      present study explores this discrepancy by investigating whether visual MMN
      (vMMN) effects can be obtained in written Chinese single-character word
      recognition. While participants were engaged in a non-linguistic distraction
      task, we measured Event-Related Potentials (ERPs) time-locked to perifoveally
      presented real and pseudo- characters matched in overall visual-orthographic
      attributes. VMMN was defined as significant difference between the ERPs to
      characters presented as deviants or as standards in a context of non-characters.
      For the native Chinese readers, af ter sub-lexical structural detection from 120
      160 ms, only real characters elicited vMMN at the interval of 170-210 ms,
      suggesting that lexical information in Chinese words is processed early and
      automatically. In a later window of 340-380 ms, both real and pseudo- characters
      yielded vMMNs. In a control group of non-Chinese participants, no evidence of
      vMMN was found for either real or pseudo-characters. Taken together, these
      results suggest that long-term memory representations for real characters may
      enable their early processing even in unattended conditions.

PMID- 29358678
TI  - Microbiology needs champions on-screen.

PMID- 29358679
TI  - Even malaria parasites watch their host's diet.

PMID- 29358680
TI  - Let them eat fruit.

PMID- 29358676
TI  - Homeolog expression analysis in an allotriploid non-model crop via integration of
      transcriptomics and proteomics.
AB  - The fate of doubled genes, from allopolyploid or autopolyploid origin, is
      controlled at multiple levels, resulting in the modern day cultivars. We studied
      the root growth of 3 different triploid banana cultivars under control and
      osmotic stress conditions. The root growth of the allopolyploid ABB cultivar was
      42% higher under control and 61% higher under osmotic stress. By integrating
      transcriptomics and proteomics, we studied the gene expression of all 3
      cultivars, resulting in 2,749 identified root proteins. 383 gene loci displayed
      genotype specific differential expression whereof 252 showed at least one Single
      Amino Acid Polymorphism (SAAP). In the ABB cultivar, allele expressions
      supposedly follow a 1/3 and 2/3 pattern for respectively the A and the B allele.
      Using transcriptome read alignment to assess the homeoallelic contribution we
      found that 63% of the allele specific genes deviated from this expectation. 32
      gene loci even did not express the A allele. The identified ABB allele- specific
      proteins correlate well with the observed growth phenotype as they are enriched
      in energy related functions such as ATP metabolic processes, nicotinamide
      nucleotide metabolic processes, and glycolysis.

PMID- 29358677
TI  - Collective responses in electrical activities of neurons under field coupling.
AB  - Synapse coupling can benefit signal exchange between neurons and information
      encoding for neurons, and the collective behaviors such as synchronization and
      pattern selection in neuronal network are often discussed under chemical or
      electric synapse coupling. Electromagnetic induction is considered at molecular
      level when ion currents flow across the membrane and the ion concentration is
      fluctuated. Magnetic flux describes the effect of time-varying electromagnetic
      field, and memristor bridges the membrane potential and magnetic flux according
      to the dimensionalization requirement. Indeed, field coupling can contribute to
      the signal exchange between neurons by triggering superposition of electric field
      when synapse coupling is not available. A chain network is designed to
      investigate the modulation of field coupling on the collective behaviors in
      neuronal network connected by electric synapse between adjacent neurons. In the
      chain network, the contribution of field coupling from each neuron is described
      by introducing appropriate weight dependent on the position distance between two
      neurons. Statistical factor of synchronization is calculated by changing the
      external stimulus and weight of field coupling. It is found that the
      synchronization degree is dependent on the coupling intensity and weight, the
      synchronization, pattern selection of network connected with gap junction can be
      modulated by field coupling.

PMID- 29358681
TI  - Decoding glycan recognition by bacterial toxins.

PMID- 29358682
TI  - A multimodal antiretroviral protein.

PMID- 29358683
TI  - Sieving through gut models of colonization resistance.
AB  - The development of innovative high-throughput genomics and metabolomics
      technologies has considerably expanded our understanding of the commensal
      microorganisms residing within the human body, collectively termed the
      microbiota. In recent years, the microbiota has been reported to have important
      roles in multiple aspects of human health, pathology and host-pathogen
      interactions. One function of commensals that has attracted particular interest
      is their role in protection against pathogens and pathobionts, a concept known as
      colonization resistance. However, pathogens are also able to sense and exploit
      the microbiota during infection. Therefore, obtaining a holistic understanding of
      colonization resistance mechanisms is essential for the development of microbiome
      based and microbiome-targeting therapies for humans and animals. Achieving this
      is dependent on utilizing physiologically relevant animal models. In this
      Perspective, we discuss the colonization resistance functions of the gut
      microbiota and sieve through the advantages and limitations of murine models
      commonly used to study such mechanisms within the context of enteric bacterial
      infection.

PMID- 29358685
TI  - Progress in mitochondrial replacement therapies.
AB  - Mitochondrial DNA is maternally inherited, and pathogenic mutations cause a range
      of life-limiting conditions. Recent studies indicate that transmission of
      pathogenic mutations may be prevented by reproductive technologies designed to
      replace the mitochondria in eggs from affected women.

PMID- 29358684
TI  - Building and decoding ubiquitin chains for mitophagy.
AB  - Mitochondria produce energy in the form of ATP via oxidative phosphorylation. As
      defects in oxidative phosphorylation can generate harmful reactive oxygen
      species, it is important that damaged mitochondria are efficiently removed via a
      selective form of autophagy known as mitophagy. Owing to a combination of cell
      biological, structural and proteomic approaches, we are beginning to understand
      the mechanisms by which ubiquitin-dependent signals mark damaged mitochondria for
      mitophagy. This Review discusses the biochemical steps and regulatory mechanisms
      that promote the conjugation of ubiquitin to damaged mitochondria via the PTEN
      induced putative kinase 1 (PINK1) and the E3 ubiquitin-protein ligase parkin and
      how ubiquitin chains promote autophagosomal capture. Recently discovered roles
      for parkin and PINK1 in the suppression of mitochondrial antigen presentation
      provide alternative models for how this pathway promotes the survival of neurons.
      A deeper understanding of these processes has major implications for
      neurodegenerative diseases, including Parkinson disease, where defects in
      mitophagy and other forms of selective autophagy are prominent.

PMID- 29358686
TI  - Stress responses: Reversible sequestration over irreversible aggregation.

PMID- 29358687
TI  - Mitochondria: The needless PINK1.

PMID- 29358688
TI  - LRIG2 is a growth suppressor of Hec-1A and Ishikawa endometrial adenocarcinoma
      cells by regulating PI3K/AKT- and EGFR-mediated apoptosis and cell-cycle.
AB  - Although endometrial cancer is the most common type of gynecological malignancy
      in developed countries, its molecular etiology is not well understood. Leucine
      rich repeat and immunoglobulin-like domain 2 (LRIG2) is an evolutionarily
      conserved gene, but its functions in the endometrium are unknown. In this study,
      we found that LRIG2 is highly downregulated in endometrial adenocarcinoma
      patients and that it functions as a tumor suppressor. LRIG2 induced the
      mitochondrion-mediated apoptotic pathways by regulating stoichiometric balance
      among BCL-2 family proteins, whereby pro-survival members, MCL-1 and BCL-xL, were
      downregulated and pro-apoptotic BAK and BAX were upregulated. LRIG2 also
      inhibited proliferation of the Hec-1A and Ishikawa endometrial adenocarcinoma
      cells by upregulating p21. LRIG2 induced BAX- and BAK-dependent cell death that
      was efficiently prevented by MCL-1 overexpression. Furthermore, we found that
      LRIG2 unexpectedly phosphor-activates phosphoinositide 3-kinase (PI3K)/AKT and
      epidermal growth factor receptor (EGFR), which are conventionally accepted as
      survival signaling cues in diverse types of cancer. We observed that PI3K/AKT and
      EGFR serve as key kinases that have roles as growth suppressors of Hec-1A
      endometrial cancer cells by mediating the LRIG2-induced modulation of the BCL-2
      family of proteins and p21. In vivo delivery of antisense DNAs against LRIG2
      promoted the Hec-1A endometrial tumor growth in a xenograft mouse model, and
      immunoblotting of these tumor extracts showed consistent modulation of AKT, EGFR,
      the BCL-2 family members, and p21. Thus, our results demonstrated that LRIG2 is a
      growth suppressor of endometrial adenocarcinoma cells.

PMID- 29358689
TI  - Engineering the vibrational coherence of vision into a synthetic molecular
      device.
AB  - The light-induced double-bond isomerization of the visual pigment rhodopsin
      operates a molecular-level optomechanical energy transduction, which triggers a
      crucial protein structure change. In fact, rhodopsin isomerization occurs
      according to a unique, ultrafast mechanism that preserves mode-specific
      vibrational coherence all the way from the reactant excited state to the primary
      photoproduct ground state. The engineering of such an energy-funnelling function
      in synthetic compounds would pave the way towards biomimetic molecular machines
      capable of achieving optimum light-to-mechanical energy conversion. Here we use
      resonance and off-resonance vibrational coherence spectroscopy to demonstrate
      that a rhodopsin-like isomerization operates in a biomimetic molecular switch in
      solution. Furthermore, by using quantum chemical simulations, we show why the
      observed coherent nuclear motion critically depends on minor chemical
      modifications capable to induce specific geometric and electronic effects. This
      finding provides a strategy for engineering vibrationally coherent motions in
      other synthetic systems.

PMID- 29358690
TI  - Radiographic Knee Osteoarthritis and Knee Pain: Cross-sectional study from Five
      Different Racial/Ethnic Populations.
AB  - The weak correlation between pain and structural changes in knee osteoarthritis
      is widely reported. In a previous within-person, knee-matched case-control study
      among Caucasians, the severity of radiographic osteoarthritis (ROA) was strongly
      associated with both the presence of frequent knee pain and pain severity. We
      studied the association between ROA and knee pain in five racial/ethnic
      populations by using the same method. Subjects were selected from China; Japan;
      Korea and the United States. Among subjects with knees discordant for either
      frequent knee pain or pain severity, we examined the relationship between ROA and
      the presence of frequent knee pain using conditional logistic regression, and
      between ROA and pain severity using a stratified proportional odds model with an
      amalgamating conditional likelihood. In total, 252 urban Chinese, 221 rural
      Chinese, 297 Japanese, 122 Korean, 1,735 Caucasian, and 394 African-American
      patients were included. There was a strong dose-response relationship between the
      severity of ROA and the prevalence of frequent knee pain in all five
      racial/ethnic populations. Even mild ROA was significantly associated with
      frequent knee pain. In addition, ROA was also strongly associated with the
      severity of knee pain. These results show that structural pathology is associated
      with knee pain in different ethnic populations.

PMID- 29358692
TI  - Author Correction: Limits of Risk Predictability in a Cascading Alternating
      Renewal Process Model.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29358693
TI  - Proteomic evidences for microcystin-RR-induced toxicological alterations in mice
      liver.
AB  - This study deals with the isolation and purification of an important variant of
      microcystins namely microcystin-RR (MCYST-RR) from Microcystis aeruginosa and
      reports its effects on mice liver protein profile and cellular functions. Protein
      profiling by 2-dimensional gel electrophoresis revealed changes in the number and
      accumulation of protein spots in liver of mice treated with different
      concentrations of MCYST-RR. Untreated (control) mice liver showed 368 protein
      spots while the number was 355, 348 and 332 in liver of mice treated with 200,
      300 and 400 ug kg body wt-1 of MCYST-RR respectively. Altogether 102, 97, and 92
      spots were differentially up-accumulated and 93, 91, and 87 spots were down-
      accumulated respectively with the treatment of 200, 300, 400 ug kg body wt-1.
      Eighteen differentially accumulated proteins present in all the four conditions
      were identified by MALDI-TOF MS. Of these eighteen proteins, 12 appeared to be
      involved in apoptosis/toxicological manifestations. Pathway analysis by Reactome
      and PANTHER database also mapped the identified proteins to programmed cell
      death/apoptosis clade. That MCYST-RR induces apoptosis in liver tissues was also
      confirmed by DNA fragmentation assay. Results of this study elucidate the
      proteomic basis for the hepatotoxicity of MCYST-RR which is otherwise poorly
      understood till date.

PMID- 29358695
TI  - "It just forces hardship": impacts of government financial penalties on non
      vaccinating parents.
AB  - Despite strong evidence confirming vaccination is safe and effective, some
      parents choose not to vaccinate their children. In 2016, the Australian
      Government introduced legislation strengthening links between vaccination
      compliance and some government payments. We interviewed thirty-one non
      vaccinating parents about the impacts of this policy. Data analysis produced
      three key themes: 'questioning policy integrity', 'minimising impact' and
      'holding my ground'. Affected parents offset reduced income by removing children
      from early childhood learning, reducing work commitments, moving residence to
      reduce living costs and accessing informal childcare arrangements. Parents
      reported a greater commitment to their decision not to vaccinate and an increased
      desire to maintain control over health choices for their children including an
      unprecedented willingness to become involved in protest action. Our study
      identifies why financial penalties have not been an effective policy measure for
      this sample of non-vaccinating parents, an understanding which may assist in the
      development of future legislation.

PMID- 29358691
TI  - Re-analysis of public genetic data reveals a rare X-chromosomal variant
      associated with type 2 diabetes.
AB  - The reanalysis of existing GWAS data represents a powerful and cost-effective
      opportunity to gain insights into the genetics of complex diseases. By
      reanalyzing publicly available type 2 diabetes (T2D) genome-wide association
      studies (GWAS) data for 70,127 subjects, we identify seven novel associated
      regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP
      genes), one by a low-frequency (EHMT2), and one driven by a rare variant in
      chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in
      males. rs146662057 is located within an active enhancer associated with the
      expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin
      sensitivity, and exhibits allelic specific activity in muscle cells. Beyond
      providing insights into the genetics and pathophysiology of T2D, these results
      also underscore the value of reanalyzing publicly available data using novel
      genetic resources and analytical approaches.

PMID- 29358694
TI  - Maternal whole blood cell miRNA-340 is elevated in gestational diabetes and
      inversely regulated by glucose and insulin.
AB  - The number of pregnancies complicated by gestational diabetes (GDM) is increasing
      worldwide. To identify novel characteristics of GDM, we studied miRNA profiles of
      maternal and fetal whole blood cells (WBCs) from GDM and normal glucose tolerant
      (NGT) pregnant women matched for body mass index and maternal age. After
      adjustment for maternal weight gain and pregnancy week, we identified 29 mature
      micro-RNAs (miRNAs) up-regulated in GDM, one of which, i.e., miRNA-340, was
      validated by qPCR. mRNA and protein expression of PAIP1, a miRNA-340 target gene,
      was found down-regulated in GDM women, accordingly. In lymphocytes derived from
      the mothers' blood and treated in vitro, insulin increased and glucose reduced
      miRNA-340 expression. In fetal cord blood samples, no associations of miRNA-340
      with maternal GDM were observed. Our results provide evidence for insulin-induced
      epigenetic, i.e., miRNA-dependent, programming of maternal WBCs in GDM.

PMID- 29358696
TI  - Land-surface initialisation improves seasonal climate prediction skill for maize
      yield forecast.
AB  - Seasonal crop yield forecasting represents an important source of information to
      maintain market stability, minimise socio-economic impacts of crop losses and
      guarantee humanitarian food assistance, while it fosters the use of climate
      information favouring adaptation strategies. As climate variability and extremes
      have significant influence on agricultural production, the early prediction of
      severe weather events and unfavourable conditions can contribute to the
      mitigation of adverse effects. Seasonal climate forecasts provide additional
      value for agricultural applications in several regions of the world. However,
      they currently play a very limited role in supporting agricultural decisions in
      Europe, mainly due to the poor skill of relevant surface variables. Here we show
      how a combined stress index (CSI), considering both drought and heat stress in
      summer, can predict maize yield in Europe and how land-surface initialised
      seasonal climate forecasts can be used to predict it. The CSI explains on average
      nearly 53% of the inter-annual maize yield variability under observed climate
      conditions and shows how concurrent heat stress and drought events have
      influenced recent yield anomalies. Seasonal climate forecast initialised with
      realistic land-surface achieves better (and marginally useful) skill in
      predicting the CSI than with climatological land-surface initialisation in south
      eastern Europe, part of central Europe, France and Italy.

PMID- 29358697
TI  - Hyperbaric oxygen reduces inflammation, oxygenates injured muscle, and
      regenerates skeletal muscle via macrophage and satellite cell activation.
AB  - Hyperbaric oxygen treatment (HBO) promotes rapid recovery from soft tissue
      injuries. However, the healing mechanism is unclear. Here we assessed the effects
      of HBO on contused calf muscles in a rat skeletal muscle injury model. An
      experimental HBO chamber was developed and rats were treated with 100% oxygen,
      2.5 atmospheres absolute for 2 h/day after injury. HBO reduced early lower limb
      volume and muscle wet weight in contused muscles, and promoted muscle isometric
      strength 7 days after injury. HBO suppressed the elevation of circulating
      macrophages in the acute phase and then accelerated macrophage invasion into the
      contused muscle. This environment also increased the number of proliferating and
      differentiating satellite cells and the amount of regenerated muscle fibers. In
      the early phase after injury, HBO stimulated the IL-6/STAT3 pathway in contused
      muscles. Our results demonstrate that HBO has a dual role in decreasing
      inflammation and accelerating myogenesis in muscle contusion injuries.

PMID- 29358698
TI  - Production of Wilson Disease Model Rabbits with Homology-Directed Precision Point
      Mutations in the ATP7B Gene Using the CRISPR/Cas9 System.
AB  - CRISPR/Cas9 has recently been developed as an efficient genome engineering tool.
      The rabbit is a suitable animal model for studies of metabolic diseases. In this
      study, we generated ATP7B site-directed point mutation rabbits to simulate a
      major mutation type in Asians (p. Arg778Leu) with Wilson disease (WD) by using
      the CRISPR/Cas9 system combined with single-strand DNA oligonucleotides (ssODNs).
      The efficiency of the precision point mutation was 52.94% when zygotes were
      injected 14 hours after HCG treatment and was significantly higher than that of
      zygotes injected 19 hours after HCG treatment (14.29%). The rabbits carrying the
      allele with mutant ATP7B died at approximately three months of age. Additionally,
      the copper content in the livers of rabbits at the onset of WD increased nine
      fold, a level similar to the five-fold increase observed in humans with WD. Thus,
      the efficiency of precision point mutations increases when RNAs are injected into
      zygotes at earlier stages, and the ATP7B mutant rabbits are a potential model for
      human WD disease with applications in pathological analysis, clinical treatment
      and gene therapy research.

PMID- 29358699
TI  - GSK3beta modulates NF-kappaB activation and RelB degradation through site
      specific phosphorylation of BCL10.
AB  - Glycogen synthase kinase 3beta (GSK3beta) is a ubiquitously expressed
      serine/threonine kinase involved in the regulation of various cellular functions,
      such as energy homoeostasis, cell growth and developmental processes. More
      recently, GSK3beta has been identified as a part of a protein complex involved in
      the regulation of the CARMA1-BCL10-MALT1 complex (CBM complex) formation, which
      is a key signalling event upon antigen receptor engagement of B and T cells,
      required for the activation of the NF-kappaB and JNK pathways. However,
      conflicting reports have been published regarding the role of GSK3beta for the
      activation of the NF-kappaB signalling pathways. Therefore, we aimed to determine
      the impact of GSK3beta on the NF-kappaB signalling induced upon T cell
      activation. Blocking GSK3beta by either pharmacologic inhibitors (SB216763 and
      SB415286) or by RNAi caused a reduced proteolysis of the MALT1 targets CYLD1,
      BCL10 and RelB as well as diminished IkappaBalpha degradation, NF-kappaB DNA
      binding and NF-kappaB activity. This negative effect on NF-kappaB appears to be
      due to a diminished CBM complex formation caused by a reduced BCL10
      phosphorylation. Taken together, we provide here evidence for a novel regulatory
      mechanism by which GSK3beta affects NF-kappaB signalling in activated T cells.

PMID- 29358700
TI  - BIM and NOXA are mitochondrial effectors of TAF6delta-driven apoptosis.
AB  - TAF6delta is a pro-apoptotic splice variant of the RNA polymerase II general
      transcription factor, TAF6, that can dictate life vs. death decisions in animal
      cells. TAF6delta stands out from classical pro-apoptotic proteins because it is
      encoded by a gene that is essential at the cellular level, and because it
      functions as a component of the basal transcription machinery. TAF6delta has been
      shown to modulate the transcriptome landscape, but it is not known if changes in
      gene expression trigger apoptosis nor which TAF6delta-regulated genes contribute
      to cell death. Here we used microarrays to interrogate the genome-wide impact of
      TAF6delta on transcriptome dynamics at temporal resolution. The results revealed
      changes in pro-apoptotic BH3-only mitochondrial genes that correlate tightly with
      the onset of cell death. These results prompted us to test and validate a role
      for the mitochondrial pathway by showing that TAF6delta expression causes
      cytochrome c release into the cytoplasm. To further dissect the mechanism by
      which TAF6delta drives apoptosis, we pinpointed BIM and NOXA as candidate
      effectors. siRNA experiments showed that both BIM and NOXA contribute to
      TAF6delta-dependent cell death. Our results identify mitochondrial effectors of
      TAF6delta-driven apoptosis, thereby providing the first of mechanistic framework
      underlying the atypical TAF6delta apoptotic pathway's capacity to intersect with
      the classically defined apoptotic machinery to trigger cell death.

PMID- 29358701
TI  - Insights into cerebral haemodynamics and oxygenation utilising in vivo mural cell
      imaging and mathematical modelling.
AB  - The neurovascular mechanisms underpinning the local regulation of cerebral blood
      flow (CBF) and oxygen transport remain elusive. In this study we have combined
      novel in vivo imaging of cortical microvascular and mural cell architecture with
      mathematical modelling of blood flow and oxygen transport, to provide new
      insights into CBF regulation that would be inaccessible in a conventional
      experimental context. Our study indicates that vasoconstriction of smooth muscle
      actin-covered vessels, rather than pericyte-covered capillaries, induces stable
      reductions in downstream intravascular capillary and tissue oxygenation. We also
      propose that seemingly paradoxical observations in the literature around reduced
      blood velocity in response to arteriolar constrictions might be caused by a
      propagation of constrictions to upstream penetrating arterioles. We provide
      support for pericytes acting as signalling conduits for upstream smooth muscle
      activation, and erythrocyte deformation as a complementary regulatory mechanism.
      Finally, we caution against the use of blood velocity as a proxy measurement for
      flow. Our combined imaging-modelling platform complements conventional
      experimentation allowing cerebrovascular physiology to be probed in unprecedented
      detail.

PMID- 29358702
TI  - Distinct domain switching in Nd0.05Ce0.95CoIn5 at low and high fields.
AB  - Nd0.05Ce0.95CoIn5 features a magnetic field-driven quantum phase transition that
      separates two antiferromagnetic phases with an identical magnetic structure
      inside the superconducting condensate. Using neutron diffraction we demonstrate
      that the population of the two magnetic domains in the two phases is affected
      differently by the rotation of the magnetic field in the tetragonal basal plane.
      In the low-field SDW-phase the domain population is only weakly affected while in
      the high-field Q-phase they undergo a sharp switch for fields around the a-axis.
      Our results provide evidence that the anisotropic spin susceptibility in both
      phases arises ultimately from spin-orbit interactions but are qualitatively
      different in the two phases. This provides evidence that the electronic structure
      is changed at the quantum phase transition, which yields a modified coupling
      between magnetism and superconductivity in the Q-phase.

PMID- 29358703
TI  - RIP3 targets pyruvate dehydrogenase complex to increase aerobic respiration in
      TNF-induced necroptosis.
AB  - Receptor-interacting protein kinase 3 (RIP3)-regulated production of reactive
      oxygen species (ROS) positively feeds back on tumour necrosis factor (TNF)
      induced necroptosis, a type of programmed necrosis. Glutamine catabolism is known
      to contribute to RIP3-mediated ROS induction, but the major contributor is
      unknown. Here, we show that RIP3 activates the pyruvate dehydrogenase complex
      (PDC, also known as PDH), the rate-limiting enzyme linking glycolysis to aerobic
      respiration, by directly phosphorylating the PDC E3 subunit (PDC-E3) on T135.
      Upon activation, PDC enhances aerobic respiration and subsequent mitochondrial
      ROS production. Unexpectedly, mixed-lineage kinase domain-like (MLKL) is also
      required for the induction of aerobic respiration, and we further show that it is
      required for RIP3 translocation to meet mitochondria-localized PDC. Our data
      uncover a regulation mechanism of PDC activity, show that PDC activation by RIP3
      is most likely the major mechanism activated by TNF to increase aerobic
      respiration and its by-product ROS, and suggest that RIP3-dependent induction of
      aerobic respiration contributes to pathologies related to oxidative stress.

PMID- 29358705
TI  - Affinity purification of cell-specific mitochondria from whole animals resolves
      patterns of genetic mosaicism.
AB  - Although mitochondria are ubiquitous organelles, they exhibit tissue-specific
      morphology, dynamics and function. Here, we describe a robust approach to isolate
      mitochondria from specific cells of diverse tissue systems in Caenorhabditis
      elegans. Cell-specific mitochondrial affinity purification (CS-MAP) yields intact
      and functional mitochondria with exceptional purity and sensitivity (>96%
      enrichment, >96% purity, and single-cell and single-animal resolution), enabling
      comparative analyses of protein and nucleic acid composition between organelles
      isolated from distinct cellular lineages. In animals harbouring a mixture of
      mutant and wild-type mitochondrial genomes, we use CS-MAP to reveal subtle mosaic
      patterns of cell-type-specific heteroplasmy across large populations of animals
      (>10,000 individuals). We demonstrate that the germline is more prone to
      propagating deleterious mitochondrial genomes than somatic lineages, which we
      propose is caused by enhanced mtDNA replication in this tissue.

PMID- 29358704
TI  - MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast
      cancer.
AB  - For many patients with breast cancer, symptomatic bone metastases appear after
      years of latency. How micrometastatic lesions remain dormant and undetectable
      before initiating colonization is unclear. Here, we describe a mechanism involved
      in bone metastatic latency of oestrogen receptor-positive (ER+) breast cancer.
      Using an in vivo genome-wide short hairpin RNA screening, we identified the
      kinase MSK1 as an important regulator of metastatic dormancy in breast cancer. In
      patients with ER+ breast cancer, low MSK1 expression associates with early
      metastasis. We show that MSK1 downregulation impairs the differentiation of
      breast cancer cells, increasing their bone homing and growth capacities. MSK1
      controls the expression of genes required for luminal cell differentiation,
      including the GATA3 and FOXA1 transcription factors, by modulating their promoter
      chromatin status. Our results indicate that MSK1 prevents metastatic progression
      of ER+ breast cancer, suggesting that stratifying patients with breast cancer as
      high or low risk for early relapse based on MSK1 expression could improve
      prognosis.

PMID- 29358706
TI  - The MTM1-UBQLN2-HSP complex mediates degradation of misfolded intermediate
      filaments in skeletal muscle.
AB  - The ubiquitin proteasome system and autophagy are major protein turnover
      mechanisms in muscle cells, which ensure stemness and muscle fibre maintenance.
      Muscle cells contain a high proportion of cytoskeletal proteins, which are prone
      to misfolding and aggregation; pathological processes that are observed in
      several neuromuscular diseases called proteinopathies. Despite advances in
      deciphering the mechanisms underlying misfolding and aggregation, little is known
      about how muscle cells manage cytoskeletal degradation. Here, we describe a
      process by which muscle cells degrade the misfolded intermediate filament
      proteins desmin and vimentin by the proteasome. This relies on the MTM1-UBQLN2
      complex to recognize and guide these misfolded proteins to the proteasome and
      occurs prior to aggregate formation. Thus, our data highlight a safeguarding
      function of the MTM1-UBQLN2 complex that ensures cytoskeletal integrity to avoid
      proteotoxic aggregate formation.

PMID- 29358708
TI  - Selective autophagy of the adaptor TRIF regulates innate inflammatory signaling.
AB  - Defective autophagy is linked to diseases such as rheumatoid arthritis, lupus and
      inflammatory bowel disease (IBD). However, the mechanisms by which autophagy
      limits inflammation remain poorly understood. Here we found that loss of the
      autophagy-related gene Atg16l1 promoted accumulation of the adaptor TRIF and
      downstream signaling in macrophages. Multiplex proteomic profiling identified
      SQSTM1 and Tax1BP1 as selective autophagy-related receptors that mediated the
      turnover of TRIF. Knockdown of Tax1bp1 increased production of the cytokines IFN
      beta and IL-1beta. Mice lacking Atg16l1 in myeloid cells succumbed to
      lipopolysaccharide-mediated sepsis but enhanced their clearance of intestinal
      Salmonella typhimurium in an interferon receptor-dependent manner. Human
      macrophages with the Crohn's disease-associated Atg16l1 variant T300A exhibited
      more production of IFN-beta and IL-1beta. An elevated interferon-response gene
      signature was observed in patients with IBD who were resistant to treatment with
      an antibody to the cytokine TNF. These findings identify selective autophagy as a
      key regulator of signaling via the innate immune system.

PMID- 29358707
TI  - The RNA-binding protein PTBP1 is necessary for B cell selection in germinal
      centers.
AB  - Antibody affinity maturation occurs in germinal centers (GCs), where B cells
      cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells
      bearing immunoglobulins with the highest affinity for antigen receive positive
      selection signals from helper T cells, which promotes their rapid proliferation.
      Here we found that the RNA-binding protein PTBP1 was needed for the progression
      of GC B cells through late S phase of the cell cycle and for affinity maturation.
      PTBP1 was required for proper expression of the c-MYC-dependent gene program
      induced in GC B cells receiving T cell help and directly regulated the
      alternative splicing and abundance of transcripts that are increased during
      positive selection to promote proliferation.

PMID- 29358709
TI  - Tumor-derived exosomes antagonize innate antiviral immunity.
AB  - Malignancies can compromise innate immunity, but the mechanisms of this are
      largely unknown. Here we found that, via tumor-derived exosomes (TEXs), cancers
      were able to transfer activated epidermal growth factor receptor (EGFR) to host
      macrophages and thereby suppress innate antiviral immunity. Screening of the
      human kinome identified the kinase MEKK2 in macrophages as an effector of TEX
      delivered EGFR that negatively regulated the antiviral immune response. In the
      context of experimental tumor implantation, MEKK2-deficient mice were more
      resistant to viral infection than were wild-type mice. Injection of TEXs into
      mice reduced innate immunity, increased viral load and increased morbidity in an
      EGFR- and MEKK2-dependent manner. MEKK2 phosphorylated IRF3, a transcription
      factor crucial for the production of type I interferons; this triggered poly
      ubiquitination of IRF3 and blocked its dimerization, translocation to the nucleus
      and transcriptional activity after viral infection. These findings identify a
      mechanism by which cancer cells can dampen host innate immunity and potentially
      cause patients with cancer to become immunocompromised.

PMID- 29358711
TI  - Volcanic dust veils from sixth century tree-ring isotopes linked to reduced
      irradiance, primary production and human health.
AB  - The large volcanic eruptions of AD 536 and 540 led to climate cooling and
      contributed to hardships of Late Antiquity societies throughout Eurasia, and
      triggered a major environmental event in the historical Roman Empire. Our set of
      stable carbon isotope records from subfossil tree rings demonstrates a strong
      negative excursion in AD 536 and 541-544. Modern data from these sites show that
      carbon isotope variations are driven by solar radiation. A model based on sixth
      century isotopes reconstruct an irradiance anomaly for AD 536 and 541-544 of
      nearly three standard deviations below the mean value based on modern data. This
      anomaly can be explained by a volcanic dust veil reducing solar radiation and
      thus primary production threatening food security over a multitude of years. We
      offer a hypothesis that persistently low irradiance contributed to remarkably
      simultaneous outbreaks of famine and Justinianic plague in the eastern Roman
      Empire with adverse effects on crop production and photosynthesis of the vitamin
      D in human skin and thus, collectively, human health. Our results provide a
      hitherto unstudied proxy for exploring the mechanisms of 'volcanic summers' to
      demonstrate the post-eruption deficiencies in sunlight and to explain the human
      consequences during such calamity years.

PMID- 29358712
TI  - Absolute spectroscopy near 7.8 MUm with a comb-locked extended-cavity quantum
      cascade-laser.
AB  - We report for the first time the frequency locking of an extended-cavity quantum
      cascade-laser (EC-QCL) to a near-infrared frequency comb. The locked laser source
      is exploited to carry out molecular spectroscopy around 7.8 MUm with a line
      centre frequency combined uncertainty of ~63 kHz. The strength of the approach,
      in view of an accurate retrieval of line centre frequencies over a spectral range
      as large as 100 cm-1, is demonstrated on the P(40), P(18) and R(31) lines of the
      fundamental rovibrational band of N2O covering the centre and edges of the P and
      R branches. The spectrometer has the potential to be straightforwardly extended
      to other spectral ranges, till 12 MUm, which is the current wavelength limit for
      commercial cw EC-QCLs.

PMID- 29358710
TI  - Single-cell genomics of multiple uncultured stramenopiles reveals underestimated
      functional diversity across oceans.
AB  - Single-celled eukaryotes (protists) are critical players in global biogeochemical
      cycling of nutrients and energy in the oceans. While their roles as primary
      producers and grazers are well appreciated, other aspects of their life histories
      remain obscure due to challenges in culturing and sequencing their natural
      diversity. Here, we exploit single-cell genomics and metagenomics data from the
      circumglobal Tara Oceans expedition to analyze the genome content and apparent
      oceanic distribution of seven prevalent lineages of uncultured heterotrophic
      stramenopiles. Based on the available data, each sequenced genome or genotype
      appears to have a specific oceanic distribution, principally correlated with
      water temperature and depth. The genome content provides hypotheses for
      specialization in terms of cell motility, food spectra, and trophic stages,
      including the potential impact on their lifestyles of horizontal gene transfer
      from prokaryotes. Our results support the idea that prominent heterotrophic
      marine protists perform diverse functions in ocean ecology.

PMID- 29358713
TI  - Ambient PM2.5 exposure and expected premature mortality to 2100 in India under
      climate change scenarios.
AB  - Premature mortality from current ambient fine particulate (PM2.5) exposure in
      India is large, but the trend under climate change is unclear. Here we estimate
      ambient PM2.5 exposure up to 2100 by applying the relative changes in PM2.5 from
      baseline period (2001-2005) derived from Coupled Model Inter-comparison Project 5
      (CMIP5) models to the satellite-derived baseline PM2.5. We then project the
      mortality burden using socioeconomic and demographic projections in the Shared
      Socioeconomic Pathway (SSP) scenarios. Ambient PM2.5 exposure is expected to peak
      in 2030 under the RCP4.5 and in 2040 under the RCP8.5 scenario. Premature
      mortality burden is expected to be 2.4-4 and 28.5-38.8% higher under RCP8.5
      scenario relative to the RCP4.5 scenario in 2031-2040 and 2091-2100,
      respectively. Improved health conditions due to economic growth are expected to
      compensate for the impact of changes in population and age distribution, leading
      to a reduction in per capita health burden from PM2.5 for all scenarios except
      the combination of RCP8.5 exposure and SSP3.

PMID- 29358714
TI  - Identification of disulfiram as a secretase-modulating compound with beneficial
      effects on Alzheimer's disease hallmarks.
AB  - ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an
      alpha-secretase in neurons. Its enzymatic activity results in secretion of a
      neuroprotective APP cleavage product (sAPP-alpha) and prevents formation of the
      amyloidogenic A-beta peptides, major hallmarks of Alzheimer's disease (AD).
      Elevated ADAM10 levels appeared to contribute to attenuation of A-beta-plaque
      formation and learning and memory deficits in AD mouse models. Therefore, it has
      been assumed that ADAM10 might represent a valuable target in AD therapy. Here we
      screened a FDA-approved drug library and identified disulfiram as a novel ADAM10
      gene expression enhancer. Disulfiram increased ADAM10 production as well as sAPP
      alpha in SH-SY5Y human neuronal cells and additionally prevented A-beta
      aggregation in an in vitro assay in a dose-dependent fashion. In addition, acute
      disulfiram treatment of Alzheimer model mice induced ADAM10 expression in
      peripheral blood cells, reduced plaque-burden in the dentate gyrus and
      ameliorated behavioral deficits. Alcohol-dependent patients are subjected to
      disulfiram-treatment to discourage alcohol-consumption. In such patients,
      enhancement of ADAM10 by disulfiram-treatment was demonstrated in peripheral
      blood cells. Our data suggest that disulfiram could be repurposed as an ADAM10
      enhancer and AD therapeutic. However, efficacy and safety has to be analyzed in
      Alzheimer patients in the future.

PMID- 29358715
TI  - Optimized Spintronic Terahertz Emitters Based on Epitaxial Grown Fe/Pt Layer
      Structures.
AB  - We report on generation of pulsed broadband terahertz radiation utilizing the
      inverse spin hall effect in Fe/Pt bilayers on MgO and sapphire substrates. The
      emitter was optimized with respect to layer thickness, growth parameters,
      substrates and geometrical arrangement. The experimentally determined optimum
      layer thicknesses were in qualitative agreement with simulations of the spin
      current induced in the ferromagnetic layer. Our model takes into account
      generation of spin polarization, spin diffusion and accumulation in Fe and Pt and
      electrical as well as optical properties of the bilayer samples. Using the device
      in a counterintuitive orientation a Si lens was attached to increase the
      collection efficiency of the emitter. The optimized emitter provided a bandwidth
      of up to 8 THz which was mainly limited by the low-temperature-grown GaAs (LT
      GaAS) photoconductive antenna used as detector and the pulse length of the pump
      laser. The THz pulse length was as short as 220 fs for a sub 100 fs pulse length
      of the 800 nm pump laser. Average pump powers as low as 25 mW (at a repetition
      rate of 75 MHz) have been used for terahertz generation. This and the general
      performance make the spintronic terahertz emitter compatible with established
      emitters based on optical rectification in nonlinear crystals.

PMID- 29358716
TI  - Impact of a motivational resistance-training programme on adherence and body
      composition in the elderly.
AB  - Lack of physical activity is one of the major causes for obesity and functional
      disability in the elderly. Including regular exercise in the elderly's lifestyle
      is not an easy task. The main objective was to analyse the effect of a
      motivational resistance-training programme on satisfying the individual's
      psychological needs, level of self-determination and body composition. A quasi
      experimental study was performed with 47 volunteers (29 females, 18 males) of 67
      75 years of age, divided into two groups: experimental (n = 27) and control (n =
      20). A 12-week intervention programme was performed, with a total of 36 sessions.
      The results of the inter-group analysis indicated significant differences in the
      post-test measurement between the experimental group and the control group (in
      favour of the experimental group) regarding basic psychological needs. The
      experimental group, in comparison to the control group, significantly decreased
      their percentage of fat mass and increased muscle mass. Body weight and BMI
      values increased in the control group, while significantly decreasing in the
      experimental group. In conclusion, the motivational resistance-training programme
      in the elderly gave rise to positive significant changes at the physical,
      psychological and social levels, according to the definition of health by the
      World Health Organization.

PMID- 29358717
TI  - Fluid network dynamics in the prefrontal cortex during multiple strategy
      switching.
AB  - Coordinated shifts of neuronal activity in the prefrontal cortex are associated
      with strategy adaptations in behavioural tasks, when animals switch from
      following one rule to another. However, network dynamics related to multiple-rule
      changes are scarcely known. We show how firing rates of individual neurons in the
      prelimbic and cingulate cortex correlate with the performance of rats trained to
      change their navigation multiple times according to allocentric and egocentric
      strategies. The concerted population activity exhibits a stable firing during the
      performance of one rule but shifted to another neuronal firing state when a new
      rule is learnt. Interestingly, when the same rule is presented a second time
      within the same session, neuronal firing does not revert back to the original
      neuronal firing state, but a new activity-state is formed. Our data indicate that
      neuronal firing of prefrontal cortical neurons represents changes in strategy and
      task-performance rather than specific strategies or rules.

PMID- 29358718
TI  - The prevalence and treatment pattern of clinically diagnosed pelvic organ
      prolapse: a Korean National Health Insurance Database-based cross-sectional study
      2009-2015.
AB  - The study aim was to evaluate the prevalence of pelvic organ prolapse using claim
      data of South Korea and to evaluate treatment patterns. The Korea National Health
      Insurance Corporation pay medical costs for most diseases. This study used Health
      Insurance Review & Assessment Service-National Inpatient Sample (HIRA-NIS) 2009
      2015. Pelvic organ prolapse was defined by diagnostic code (N81.x). Of the
      approximately 4.5 million women included in HIRA-NIS 2009-2015, 10,305 women were
      selected as having pelvic organ prolapse, and the mean age of the pelvic organ
      prolapse group was 63.9 +/- 0.2 years. The prevalence of pelvic organ prolapse
      was 180 +/- 4 per 100,000 population in women older than 50 years old. In
      logistic regression analysis, constipation increased the prevalence of all pelvic
      organ prolapse (odds ratio, 4.04; 95% confidence interval, 3.52-4.63; P < 0.01).
      The number of women requiring pessary only and surgery only were 26 +/- 2 per
      100,000 population and 89 +/- 1 per 100,000 population, respectively, for women
      over 50 years of age. The prevalence of pelvic organ prolapse was quite lower
      than in previous studies. Surgery peaked at approximately 70 years of age.
      Pessary increased dramatically among women after the age of 65.

PMID- 29358719
TI  - Investigation of Candida parapsilosis virulence regulatory factors during host
      pathogen interaction.
AB  - Invasive candidiasis is among the most life-threatening infections in patients in
      intensive care units. Although Candida albicans is the leading cause of
      candidaemia, the incidence of Candida parapsilosis infections is also rising,
      particularly among the neonates. Due to differences in their biology, these
      species employ different antifungal resistance and virulence mechanisms and also
      induce dissimilar immune responses. Previously, it has been suggested that core
      virulence effecting transcription regulators could be attractive ligands for
      future antifungal drugs. Although the virulence regulatory mechanisms of C.
      albicans are well studied, less is known about similar mechanisms in C.
      parapsilosis. In order to search for potential targets for future antifungal
      drugs against this species, we analyzed the fungal transcriptome during host
      pathogen interaction using an in vitro infection model. Selected genes with high
      expression levels were further examined through their respective null mutant
      strains, under conditions that mimic the host environment or influence
      pathogenicity. As a result, we identified several mutants with relevant
      pathogenicity affecting phenotypes. During the study we highlight three
      potentially tractable signaling regulators that influence C. parapsilosis
      pathogenicity in distinct mechanisms. During infection, CPAR2_100540 is
      responsible for nutrient acquisition, CPAR2_200390 for cell wall assembly and
      morphology switching and CPAR2_303700 for fungal viability.

PMID- 29358720
TI  - Strong Fe3+-O(H)-Pt Interfacial Interaction Induced Excellent Stability of
      Pt/NiFe-LDH/rGO Electrocatalysts.
AB  - Agglomeration-triggered deactivation of supported platinum electrocatalysts
      markedly hinders their application in methanol oxidation reaction (MOR). In this
      study, graphene-supported nickel-iron layered double hydroxide (NiFe-LDH/rGO), in
      which Fe3+ was introduced to replace Ni2+ partially in the Ni(OH)2 lattice to
      provide stronger metal-support bonding sites, was utilized to immobilize Pt
      nanoparticles (NPs). Given the optimized metal-support interfacial contact (Fe3+
      O(H)-Pt) between Pt NPs and NiFe-LDH/rGO nanosheets for Pt/NiFe-LDH/rGO
      electrocatalysts, the Pt/NiFe-LDH/rGO electrocatalysts displayed dramatically
      enhanced durability than that of Pt/Ni(OH)2/rGO counterpart as well as commercial
      Pt/C, and 86.5% of its initial catalytic activity can be maintained even after
      1200 cycles of cyclic voltammetry (CV) tests during MOR. First-principle
      calculations toward the resultant M-O(H)-Pt (M = Fe3+, Ni2+) interfacial
      structure further corroborates that the NiFe-LDH nanosheets can provide stronger
      bonding sites (via the Fe3+-O(H)-Pt bonds) to immobilize Pt NPs than those of
      Ni(OH)2 nanosheets (via the Ni2+-O(H)-Pt bonds).

PMID- 29358721
TI  - Dihydropyrimidine dehydrogenase predicts survival and response to interferon
      alpha in hepatocellular carcinoma.
AB  - Metastasis and recurrence contribute to poor prognosis of hepatocellular
      carcinoma (HCC). Recently, we reported that interferon-alpha (IFN-alpha) can
      suppress metastasis of HCC; however, the underlying mechanism has not been fully
      described. In this study, we demonstrated that expression of dihydropyrimidine
      dehydrogenase (DPYD), a pyrimidine catabolic enzyme, was dose-dependently
      downregulated by IFN-alpha in HCC tissues from nude mice. Notably, DPYD
      expression was found to be significantly increased in HCC cell lines with higher
      metastatic potentials compared with their controls. Moreover, upregulation of
      DPYD in HCC cells could promote in vitro migration, invasion, and in vivo lung
      metastasis, and inducing changes characteristic of epithelial-mesenchymal
      transition (EMT). In contrast, knockdown of DPYD inhibited these processes.
      Mechanistically, DPYD functioned as a positive regulator of EMT in HCC by
      targeting the p38/NF-kappaB/Snail1 pathway. Clinically, tissue microarray
      analysis showed that high DPYD expression was positively associated with
      aggressive tumor characteristics, including larger tumor size, tumor recurrence,
      and advanced tumor node metastasis (TNM) stage, and independently correlated with
      poorer overall survival times after curative resection. HCC patients with low
      DPYD expression have better response to IFN-alpha therapy. Taken together, our
      findings elucidate that IFN-alpha could downregulate DPYD expression to inhibit
      EMT and HCC metastasis, and suggest that DPYD might be a potential prognostic
      biomarker and a therapeutic target for HCC.

PMID- 29358723
TI  - The cross correlation properties of composite systems.
AB  - A new method is presented for characterizing cross correlations in composite
      systems described by a couple of time-dependent random variables. This method is
      based on (i) rescaling the time derivatives of the variables to make their
      variances unity and then (ii) recombining these rescaled variables into their sum
      and difference. This manipulation enables one to express the joint probability
      distribution function in a peculiar way. It is also found that the entropy of
      composite systems is not equal to the sum of entropy of each subsystem because of
      the cross correlations.

PMID- 29358722
TI  - Butyrylcholinesterase and Acetylcholinesterase polymorphisms in Multiple
      Sclerosis patients: implication in peripheral inflammation.
AB  - Multiple Sclerosis (MS) is an autoimmune disease, having not fully understood
      aetiology, and both genetic and environmental factors contribute to the
      pathogenesis of the disease. The cholinergic system has been indicated as a
      mediator of neuro-immune interactions, as well as an internal regulator of immune
      responses. The aim of the present research was to assess the associations between
      BChE and AChE genetic variations and serum cholinergic and inflammatory profiles
      in 102 Relapsing Remitting-MS patients and 117 healthy controls. An increased
      frequency of the BChE K-allele in MS patients as compared to controls was found.
      In addition, data showed that patients had higher BChE enzymatic activity, which
      is increased by the presence of the polymorphic allele and reduced amounts of
      circulating ACh. AChE polymorphism was significantly associated to reduced
      activity in both patients and controls. We propose that serum BChE and AChE
      activity may be used as a secondary markers to assess the role of non-neuronal
      cholinergic system in regulating peripheral inflammation via ACh regulation. This
      pilot study shed light on the role of the non-neuronal cholinergic system in
      immune cells to better understand MS pathogenesis. The cross-talk between the
      periphery and the CNS could have a new undescribed crucial role for MS, regarded
      as a systemic disease.

PMID- 29358724
TI  - Development of matrix metalloproteinase-targeted probes for lung inflammation
      detection with positron emission tomography.
AB  - As matrix metalloproteinases (MMPs), especially MMP-9 and MMP-12 are involved in
      the pathological processes associated with chronic obstructive pulmonary disease
      (COPD), we developed a novel radiofluorinated probe, 18F-IPFP, for MMPs-targeted
      positron emission tomography (PET). 18F-IPFP was designed by iodination of MMP
      inhibitor to enhance the affinity, and labelled with a compact prosthetic agent,
      4-nitrophenyl 2-18F-fluoropropionate (18F-NFP). As a result, IPFP demonstrated
      the highest affinity toward MMP-12 (IC50 = 1.5 nM) among existing PET probes. A
      COPD model was employed by exposing mice to cigarette smoke and the expression
      levels of MMP-9 and MMP-12 were significantly increased in the lungs.
      Radioactivity accumulation in the lungs 90 min after administration of 18F-IPFP
      was 4* higher in COPD mice than normal mice, and 10* higher than in the heart,
      muscle, and blood. Ex vivo PET confirmed the radioactivity distribution in the
      tissues and autoradiography analysis demonstrated that accumulation differences
      in the lungs of COPD mice were 2* higher than those of normal mice. These results
      suggest that 18F-IPFP is a promising probe for pulmonary imaging and expected to
      be applied to various MMP-related diseases for early diagnosis, tracking of
      therapeutic effects, and new drug development in both preclinical and clinical
      applications.

PMID- 29358725
TI  - Fine-scale landscape genomics helps explain the slow spatial spread of Wolbachia
      through the Aedes aegypti population in Cairns, Australia.
AB  - The endosymbiotic bacterium Wolbachia suppresses the capacity for arbovirus
      transmission in the mosquito Aedes aegypti, and can spread spatially through wild
      mosquito populations following local introductions. Recent introductions in
      Cairns, Australia have demonstrated slower than expected spatial spread.
      Potential reasons for this include: (i) barriers to Ae. aegypti dispersal; (ii)
      higher incidence of long-range dispersal; and (iii) intergenerational loss of
      Wolbachia. We investigated these three potential factors using genome-wide single
      nucleotide polymorphisms (SNPs) and an assay for the Wolbachia infection wMel in
      161 Ae. aegypti collected from Cairns in 2015. We detected a small but
      significant barrier effect of Cairns highways on Ae. aegypti dispersal using
      distance-based redundancy analysis and patch-based simulation analysis. We
      detected a pair of putative full-siblings in ovitraps 1312 m apart, indicating
      long-distance female movement likely mediated by human transport. We also found a
      pair of full-siblings of different infection status, indicating intergenerational
      loss of Wolbachia in the field. These three factors are all expected to
      contribute to the slow spread of Wolbachia through Ae. aegypti populations,
      though from our results it is unclear whether Wolbachia loss and long-distance
      movement are sufficiently common to reduce the speed of spatial spread
      appreciably. Our findings inform the strategic deployment of Wolbachia-infected
      mosquitoes during releases, and show how parameter estimates from laboratory
      studies may differ from those estimated using field data. Our landscape genomics
      approach can be extended to other host/symbiont systems that are being considered
      for biocontrol.

PMID- 29358726
TI  - Coalescent framework for prokaryotes undergoing interspecific homologous
      recombination.
AB  - Coalescent process for prokaryote species is theoretically considered.
      Prokaryotes undergo homologous recombination with individuals of the same species
      (intraspecific recombination) and with individuals of other species
      (interspecific recombination). This work particularly focuses on interspecific
      recombination because intraspecific recombination has been well incorporated in
      coalescent framework. We present a simulation framework for generating SNP
      (single-nucleotide polymorphism) patterns that allows external DNA integration
      into host genome from other species. Using this simulation tool, msPro, we
      observed that the joint processes of intra- and interspecific recombination
      generate complex SNP patterns. The direct effect of interspecific recombination
      includes increased polymorphism. Because interspecific recombination is very rare
      in nature, it generates regions with exceptionally high polymorphism. Following
      interspecific recombination, intraspecific recombination cuts the integrated
      external DNA into small fragments, generating a complex SNP pattern that appears
      as if external DNA was integrated multiple times. The insight gained from our
      work using the msPro simulator will be useful for understanding and evaluating
      the relative contributions of intra- and interspecific recombination events in
      generating complex SNP patters in prokaryotes.

PMID- 29358727
TI  - Inference of multiple-wave admixtures by length distribution of ancestral tracks.
AB  - The ancestral tracks in admixed genomes are valuable for population history
      inference. While a few methods have been developed to infer admixture history
      based on ancestral tracks, these methods suffer the same flaw: only population
      admixture history under some specific models can be inferred. In addition, the
      inference of history might be biased or even unreliable if the specific model
      deviates from the real situation. To address this problem, we firstly proposed a
      general discrete admixture model to describe the admixture history with multiple
      ancestral populations and multiple-wave admixtures. We next deduced the length
      distribution of ancestral tracks under the general discrete admixture model. We
      further developed a new method, MultiWaver, to explore multiple-wave admixture
      histories. Our method could automatically determine an optimal admixture model
      based on the length distribution of ancestral tracks, and estimate the
      corresponding parameters under this optimal model. Specifically, we used a
      likelihood ratio test (LRT) to determine the number of admixture waves, and
      implemented an expectation-maximization (EM) algorithm to estimate parameters. We
      used simulation studies to validate the reliability and effectiveness of our
      method. Finally, good performance was observed when our method was applied to
      real data sets of African Americans and Mexicans, and new insights were gained
      into the admixture history of Uyghurs and Hazaras.

PMID- 29358728
TI  - Raman spectroscopy of graphene under ultrafast laser excitation.
AB  - The equilibrium optical phonons of graphene are well characterized in terms of
      anharmonicity and electron-phonon interactions; however, their non-equilibrium
      properties in the presence of hot charge carriers are still not fully explored.
      Here we study the Raman spectrum of graphene under ultrafast laser excitation
      with 3 ps pulses, which trade off between impulsive stimulation and spectral
      resolution. We localize energy into hot carriers, generating non-equilibrium
      temperatures in the ~1700-3100 K range, far exceeding that of the phonon bath,
      while simultaneously detecting the Raman response. The linewidths of both G and
      2D peaks show an increase as function of the electronic temperature. We explain
      this as a result of the Dirac cones' broadening and electron-phonon scattering in
      the highly excited transient regime, important for the emerging field of graphene
      based photonics and optoelectronics.

PMID- 29358730
TI  - Author Correction: In situ assembly of Ag nanoparticles (AgNPs) on porous
      silkworm cocoon-based wound film: enhanced antimicrobial and wound healing
      activity.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29358729
TI  - Pretreatment of wheat straw leads to structural changes and improved enzymatic
      hydrolysis.
AB  - Wheat straw (WS) is a potential biomass for production of monomeric sugars.
      However, the enzymatic hydrolysis ratio of cellulose in WS is relatively low due
      to the presence of lignin and hemicellulose. To enhance the enzymatic conversion
      of WS, we tested the impact of three different pretreatments, e.g. sulfuric acid
      (H2SO4), sodium hydroxide (NaOH), and hot water pretreatments to the enzymatic
      digestions. Among the three pretreatments, the highest cellulose conversion rate
      was obtained with the 4% NaOH pretreatment at 121  degrees C (87.2%). In
      addition, NaOH pretreatment was mainly effective in removing lignin, whereas the
      H2SO4 pretreatment efficiently removed hemicellulose. To investigate results of
      pretreated process for enhancement of enzyme-hydolysis to the WS, we used
      scanning electron microscopy, X-ray diffraction, and Fourier transform infrared
      spectroscopy to analyze structural changes of raw and treated materials. The
      structural analysis indicated that after H2SO4 and NaOH pretreatments, most of
      the amorphous cellulose and partial crystalline cellulose were hydrolyzed during
      enzymatic hydrolysis. The findings of the present study indicate that WS could be
      ideal materials for production of monomeric sugars with proper pretreatments and
      effective enzymatic base hydrolysis.

PMID- 29358731
TI  - Aminode: Identification of Evolutionary Constraints in the Human Proteome.
AB  - Evolutionarily constrained regions (ECRs) are a hallmark for sites of critical
      importance for a protein's structure or function. ECRs can be inferred by
      comparing the amino acid sequences from multiple protein homologs in the context
      of the evolutionary relationships that link the analyzed proteins. The
      compilation and analysis of the datasets required to infer ECRs, however, are
      time consuming and require skills in coding and bioinformatics, which can limit
      the use of ECR analysis in the biomedical community. Here, we developed Aminode,
      a user-friendly webtool for the routine and rapid inference of ECRs. Aminode is
      pre-loaded with the results of the analysis of the whole human proteome compared
      with proteomes from 62 additional vertebrate species. Profiles of the relative
      rates of amino acid substitution and ECR maps of human proteins are available for
      immediate search and download on the Aminode website. Aminode can also be used
      for custom analyses of protein families of interest. Interestingly, mapping of
      known missense variants shows great enrichment of pathogenic variants and
      depletion of non-pathogenic variants in Aminode-generated ECRs, suggesting that
      ECR analysis may help evaluate the potential pathogenicity of variants of unknown
      significance. Aminode is freely available at http://www.aminode.org .

PMID- 29358733
TI  - Glutamine metabolism, the Achilles heel for medulloblastoma tumor.

PMID- 29358732
TI  - Echocardiographic validation of pulmonary hypertension due to heart failure with
      reduced ejection fraction in mice.
AB  - Pulmonary hypertension (PH) associated with left heart diseases is the most
      prevalent cause of PH. The scarcity of studies exploring the pathophysiology and
      therapies of group II PH resides in the lack of validated small animal models
      with non-invasive determination of the presence and severity of PH. Heart failure
      (HF) was induced in mice by coronary artery ligation. Mice developed PH as
      evidenced by an elevated right ventricular (RV) systolic pressure and RV
      hypertrophy. Detailed non-invasive echocardiographic analysis on the left and
      right ventricles showed impaired left ventricular (LV) systolic and diastolic
      function. In addition, RV hypertrophy was confirmed by echo and accompanied by
      impaired function as well as increased pulmonary resistance. Correlation analysis
      validated the use of the LV wall-motion score index (WMSI) at a threshold value
      of >=2.0 as a powerful and reliable indicator for the presence of PH and RV
      dysfunction. Echocardiography is an accurate non-invasive technique to diagnose
      PH in a HF mouse model. Moreover, an echocardiographic parameter of infarct size
      and LV function, the LV WMSI, reliably correlates with the presence of PH, RV
      hypertrophy and RV dysfunction and could be used to improve efficiency and design
      of pre-clinical studies.

PMID- 29358734
TI  - Quantitative proteomics identifies redox switches for global translation
      modulation by mitochondrially produced reactive oxygen species.
AB  - The generation of reactive oxygen species (ROS) is inevitably linked to life.
      However, the precise role of ROS in signalling and specific targets is largely
      unknown. We perform a global proteomic analysis to delineate the yeast redoxome
      to a depth of more than 4,300 unique cysteine residues in over 2,200 proteins.
      Mapping of redox-active thiols in proteins exposed to exogenous or endogenous
      mitochondria-derived oxidative stress reveals ROS-sensitive sites in several
      components of the translation apparatus. Mitochondria are the major source of
      cellular ROS. We demonstrate that increased levels of intracellular ROS caused by
      dysfunctional mitochondria serve as a signal to attenuate global protein
      synthesis. Hence, we propose a universal mechanism that controls protein
      synthesis by inducing reversible changes in the translation machinery upon
      modulating the redox status of proteins involved in translation. This crosstalk
      between mitochondria and protein synthesis may have an important contribution to
      pathologies caused by dysfunctional mitochondria.

PMID- 29358735
TI  - Microbial community assembly in wild populations of the fruit fly Drosophila
      melanogaster.
AB  - Animals are routinely colonized by microorganisms. Despite many studies
      documenting the microbial taxa associated with animals, the pattern and
      ecological determinants of among-animal variation in microbial communities are
      poorly understood. This study quantified the bacterial communities associated
      with natural populations of Drosophila melanogaster. Across five collections,
      each fly bore 16-78 OTUs, predominantly of the Acetobacteraceae,
      Lactobacillaceae, and Enterobacteriaceae. Positive relationships, mostly among
      related OTUs, dominated both the significant co-occurrences and co-association
      networks among bacteria, and OTUs with important network positions were generally
      of intermediate abundance and prevalence. The prevalence of most OTUs was well
      predicted by a neutral model suggesting that ecological drift and passive
      dispersal contribute significantly to microbiome composition. However, some
      Acetobacteraceae and Lactobacillaceae were present in more flies than predicted,
      indicative of superior among-fly dispersal. These taxa may be well-adapted to the
      Drosophila habitat from the perspective of dispersal as the principal benefit of
      the association to the microbial partners. Taken together, these patterns
      indicate that both stochastic processes and deterministic processes relating to
      the differential capacity for persistence in the host habitat and transmission
      between hosts contribute to bacterial community assembly in Drosophila
      melanogaster.

PMID- 29358736
TI  - Calling from distance: attraction of soil bacteria by plant root volatiles.
AB  - Plants release a wide set of secondary metabolites including volatile organic
      compounds (VOCs). Many of those compounds are considered to function as defense
      against herbivory, pests, and pathogens. However, little knowledge exists about
      the role of belowground plant VOCs for attracting beneficial soil microorganisms.
      We developed an olfactometer system to test the attraction of soil bacteria by
      VOCs emitted by Carex arenaria roots. Moreover, we tested whether infection of C.
      arenaria with the fungal pathogen Fusarium culmorum modifies the VOCs profile and
      bacterial attraction. The results revealed that migration of distant bacteria in
      soil towards roots can be stimulated by plant VOCs. Upon fungal infection, the
      blend of root VOCs changed and specific bacteria with antifungal properties were
      attracted. Tests with various pure VOCs indicated that those compounds can
      diffuse over long distance but with different diffusion abilities. Overall, this
      work highlights the importance of plant VOCs in belowground long-distance plant
      microbe interactions.

PMID- 29358737
TI  - Inverse-Designed Broadband All-Dielectric Electromagnetic Metadevices.
AB  - This paper presents a platform combining an inverse electromagnetic design
      computational method with additive manufacturing to design and fabricate all
      dielectric metadevices. As opposed to conventional flat metasurface-based devices
      that are composed of resonant building blocks resulting in narrow band operation,
      the proposed design approach creates non-resonant, broadband (Deltalambda/lambda
      up to >50%) metadevices based on low-index dielectric materials. High-efficiency
      (transmission >60%), thin (<=2lambda) metadevices capable of polarization
      splitting, beam bending, and focusing are proposed. Experimental demonstrations
      are performed at millimeter-wave frequencies using 3D-printed devices. The
      proposed platform can be readily applied to the design and fabrication of
      electromagnetic and photonic metadevices spanning microwave to optical
      frequencies.

PMID- 29358739
TI  - Mice use robust and common strategies to discriminate natural scenes.
AB  - Mice use vision to navigate and avoid predators in natural environments. However,
      their visual systems are compact compared to other mammals, and it is unclear how
      well mice can discriminate ethologically relevant scenes. Here, we examined
      natural scene discrimination in mice using an automated touch-screen system. We
      estimated the discrimination difficulty using the computational metric structural
      similarity (SSIM), and constructed psychometric curves. However, the performance
      of each mouse was better predicted by the mean performance of other mice than
      SSIM. This high inter-mouse agreement indicates that mice use common and robust
      strategies to discriminate natural scenes. We tested several other image metrics
      to find an alternative to SSIM for predicting discrimination performance. We
      found that a simple, primary visual cortex (V1)-inspired model predicted mouse
      performance with fidelity approaching the inter-mouse agreement. The model
      involved convolving the images with Gabor filters, and its performance varied
      with the orientation of the Gabor filter. This orientation dependence was driven
      by the stimuli, rather than an innate biological feature. Together, these results
      indicate that mice are adept at discriminating natural scenes, and their
      performance is well predicted by simple models of V1 processing.

PMID- 29358738
TI  - Kinin-B1 Receptor Stimulation Promotes Invasion and is Involved in Cell-Cell
      Interaction of Co-Cultured Glioblastoma and Mesenchymal Stem Cells.
AB  - Glioblastoma multiforme (GBM) represents the most lethal brain tumour, and these
      tumours have very limited treatment options. Mesenchymal stem cells (MSC) are
      considered as candidates for advanced cell therapies, due to their tropism
      towards GBM, possibly affecting their malignancy, thus also representing a
      potential therapeutic vector. Therefore, we aimed to compare the effects of bone
      marrow-derived versus adipose-tissue-derived MSC (BM-/AT-MSC) on heterogeneous
      populations of tumour cells. This cells' interplay was addressed by the in-vitro
      two-dimensional (monolayer) and three-dimensional (spheroid) co-culture models,
      using U87 and U373 GBM cell lines, expressing genotypically different mesenchymal
      transcriptome profiles. U87 cell low mesenchymal profile expressed high levels of
      kinin receptor 1 (B1R) and their invasion was greatly enhanced by the B1R agonist
      des-Arg9-bradykinin upon BM-MSC co-culturing in 3D co-cultures. This correlated
      to significantly higher cell-cell interactions in U87/BM-MSC mixed spheroids.
      This was not observed with the U373 cells and not in AT-MSC co-cultures.
      Altogether, these data support the on-going exploration of B1R as target for
      adjuvant approach in GBM therapy. Secondly, the results emphasize the need for
      further careful exploration of the selectivity regarding the origin of MSC as
      potential candidates for cell therapies, particular in cancer, where they may
      adversely affect heterogeneous tumour cell populations.

PMID- 29358740
TI  - Quasi-continuous transition from a Fermi liquid to a spin liquid in kappa
      (ET)2Cu2(CN)3.
AB  - The Mott metal-insulator transition-a manifestation of Coulomb interactions among
      electrons-is known as a discontinuous transition. Recent theoretical studies,
      however, suggest that the transition is continuous if the Mott insulator carries
      a spin liquid with a spinon Fermi surface. Here, we demonstrate the case of a
      quasi-continuous Mott transition from a Fermi liquid to a spin liquid in an
      organic triangular-lattice system kappa-(ET)2Cu2(CN)3. Transport experiments
      performed under fine pressure tuning have found that as the Mott transition is
      approached, the Fermi liquid coherence temperature continuously falls to the
      scale of kelvins, with a divergent quasi-particle decay rate on the metal side,
      and the charge gap continuously closes on the insulator side. A Clausius
      Clapeyron analysis provides thermodynamic evidence for the extremely weak first
      order nature of the transition. These results provide additional support for the
      existence of a spinon Fermi surface, which becomes an electron Fermi surface when
      charges are delocalized.

PMID- 29358741
TI  - The structure of serum resistance-associated protein and its implications for
      human African trypanosomiasis.
AB  - Only two trypanosome subspecies are able to cause human African trypanosomiasis.
      To establish an infection in human blood, they must overcome the innate immune
      system by resisting the toxic effects of trypanolytic factor 1 and trypanolytic
      factor 2 (refs. 1,2). These lipoprotein complexes contain an active, pore-forming
      component, apolipoprotein L1 (ApoL1), that causes trypanosome cell death 3 . One
      of the two human-infective subspecies, Trypanosoma brucei rhodesiense, differs
      from non-infective trypanosomes solely by the presence of the serum resistance
      associated protein, which binds directly to ApoL1 and blocks its pore-forming
      capacity3-5. Since this interaction is the single critical event that renders T.
      b. rhodesiense human- infective, detailed structural information that allows
      identification of binding determinants is crucial to understand immune escape by
      the parasite. Here, we present the structure of serum resistance-associated
      protein and reveal the adaptations that occurred as it diverged from other
      trypanosome surface molecules to neutralize ApoL1. We also present our mapping of
      residues important for ApoL1 binding, giving molecular insight into this
      interaction at the heart of human sleeping sickness.

PMID- 29358743
TI  - Nature of the low magnetization decay on stacks of second generation
      superconducting tapes under crossed and rotating magnetic field experiments.
AB  - The extremely low decay factor on the trapped magnetic field by stacks of second
      generation high-temperature superconducting tapes reported in Appl. Phys. Lett.
      104, 232602 (2014), is in apparent contradiction with the classical results for
      the demagnetization of superconducting bulks and thin films, where the samples
      undergo a severe and progressive decay under crossed magnetic field conditions.
      Nevertheless, in this paper, we demonstrate how the theoretical approaches and
      experimental measurements on superconducting bulks, thin films, and stacks of
      superconducting tapes can be reconciled, not only under the crossed field
      configuration but also under rotating magnetic field conditions, by showing that
      the stacks of commercial tapes behave as a system of electrically unconnected
      layers preventing the deformation of profiles of current along its external
      contour. This study extends up to the consideration of using novel
      superconducting/ferromagnetic metastructures, where soft ferromagnetic films are
      interlayered, reporting a further reduction on the magnetization decay of about
      50% in the crossed field configuration. Remarkably, after applying the same
      number of cycles either of rotating or crossed magnetic field to these
      metastructures, the difference between the magnetization decay is found to be
      negligible, what demonstrates their highly superior performance when compared to
      conventional stacks of superconducting tapes.

PMID- 29358742
TI  - Increased diversity of peptidic natural products revealed by modification
      tolerant database search of mass spectra.
AB  - Peptidic natural products (PNPs) include many antibiotics and other bioactive
      compounds. While the recent launch of the Global Natural Products Social (GNPS)
      molecular networking infrastructure is transforming PNP discovery into a high
      throughput technology, PNP identification algorithms are needed to realize the
      potential of the GNPS project. GNPS relies on the assumption that each connected
      component of a molecular network (representing related metabolites) illuminates
      the 'dark matter of metabolomics' as long as it contains a known metabolite
      present in a database. We reveal a surprising diversity of PNPs produced by
      related bacteria and show that, contrary to the 'comparative metabolomics'
      assumption, two related bacteria are unlikely to produce identical PNPs (even
      though they are likely to produce similar PNPs). Since this observation
      undermines the utility of GNPS, we developed a PNP identification tool, VarQuest,
      that illuminates the connected components in a molecular network even if they do
      not contain known PNPs and only contain their variants. VarQuest reveals an order
      of magnitude more PNP variants than all previous PNP discovery efforts and
      demonstrates that GNPS already contains spectra from 41% of the currently known
      PNP families. The enormous diversity of PNPs suggests that biosynthetic gene
      clusters in various microorganisms constantly evolve to generate a unique
      spectrum of PNP variants that differ from PNPs in other species.

PMID- 29358744
TI  - NMR studies on lignocellulose deconstructions in the digestive system of the
      lower termite Coptotermes formosanus Shiraki.
AB  - Termites represent one of the most efficient lignocellulose decomposers on earth.
      The mechanism by which termites overcome the recalcitrant lignin barrier to gain
      access to embedded polysaccharides for assimilation and energy remains largely
      unknown. In the present study, softwood, hardwood, and grass lignocellulose diets
      were fed to Coptotermes formosanus workers, and structural differences between
      the original lignocellulose diets and the resulting feces were examined by
      solution-state multidimensional nuclear magnetic resonance (NMR) techniques as
      well as by complementary wet-chemical methods. Overall, our data support the view
      that lignin polymers are partially decomposed during their passage through the
      termite gut digestive system, although polysaccharide decomposition clearly
      dominates the overall lignocellulose deconstruction process and the majority of
      lignin polymers remain intact in the digestive residues. High-resolution NMR
      structural data suggested preferential removal of syringyl aromatic units in
      hardwood lignins, but non-acylated guaiacyl units as well as tricin end-units in
      grass lignins. In addition, our data suggest that termites and/or their gut
      symbionts may favor degradation of C-C-bonded beta-5 and resinol-type beta-beta
      lignin inter-monomeric units over degradation of ether-bonded beta-O-4 units,
      which is in contrast to what has been observed in typical lignin biodegradation
      undertaken by wood-decaying fungi.

PMID- 29358745
TI  - Gene annotation bias impedes biomedical research.
AB  - We found tremendous inequality across gene and protein annotation resources. We
      observed that this bias leads biomedical researchers to focus on richly annotated
      genes instead of those with the strongest molecular data. We advocate that
      researchers reduce these biases by pursuing data-driven hypotheses.

PMID- 29358746
TI  - Deactivation of Cellulase at the Air-Liquid Interface Is the Main Cause of
      Incomplete Cellulose Conversion at Low Enzyme Loadings.
AB  - Amphiphilic additives such as bovine serum albumin (BSA) and Tween have been used
      to improve cellulose hydrolysis by cellulases. However, there has been a lack of
      clarity to explain their mechanism of action in enzymatic hydrolysis of pure or
      low-lignin cellulosic substrates. In this work, a commercial Trichoderma reesei
      enzyme preparation and the amphiphilic additives BSA and Tween 20 were applied
      for hydrolysis of pure Avicel cellulose. The results showed that these additives
      only had large effects on cellulose conversion at low enzyme to substrate ratios
      when the reaction flasks were shaken. Furthermore, changes in the air-liquid
      interfacial area profoundly affected cellulose conversion, but surfactants
      reduced or prevented cellulase deactivation at the air-liquid interface. Not
      shaking the flasks or adding low amounts of surfactant resulted in near
      theoretical cellulose conversion at low enzyme loadings given enough reaction
      time. At low enzyme loadings, hydrolysis of cellulose in lignocellulosic biomass
      with low lignin content suffered from enhanced enzyme deactivation at the air
      liquid interface.

PMID- 29358747
TI  - Serum miR-375-3p increase in mice exposed to a high dose of ionizing radiation.
AB  - Exposure to high-doses of ionizing radiation (IR) leads to development of a
      strong acute radiation syndrome (ARS) in mammals. ARS manifests after a latency
      period and it is important to develop fast prognostic biomarkers for its early
      detection and assessment. Analysis of chromosomal aberrations in peripheral blood
      lymphocytes is the gold standard of biological dosimetry, but it fails after high
      doses of IR. Therefore, it is important to establish novel biomarkers of exposure
      that are fast and reliable also in the high dose range. Here, we investigated the
      applicability of miRNA levels in mouse serum. We found significantly increased
      levels of miR-375-3p following whole body exposure to 7 Gy of X-rays. In
      addition, we analyzed their levels in various organs of control mice and found
      them to be especially abundant in the pancreas and the intestine. Following a
      dose of 7 Gy, extensive cell death occurred in these tissues and this correlated
      negatively with the levels of miR-375-3p in the organs. We conclude that high
      expressing tissues of miR-375-3p may secrete this miRNA in serum following
      exposure to 7 Gy. Therefore, elevated miR-375-3p in serum may be a predictor of
      tissue damage induced by exposure to a high radiation dose.

PMID- 29358750
TI  - Partnership for callusing.

PMID- 29358748
TI  - Stress-dependent miR-980 regulation of Rbfox1/A2bp1 promotes ribonucleoprotein
      granule formation and cell survival.
AB  - Upon stress, profound post-transcriptional adjustments of gene expression occur
      in spatially restricted, subcellular, membraneless compartments, or
      ribonucleoprotein (RNP) granules, which are formed by liquid phase separation of
      RNA-binding proteins with low complexity sequence domains (LCDs). Here, we show
      that Rbfox1 is an LCD-containing protein that aggregates into liquid droplets and
      amyloid-like fibers and promiscuously joins different nuclear and cytoplasmic RNP
      granules. Using Drosophila oogenesis as an in vivo system for stress response, we
      demonstrate a mechanism by which Rbfox1 promotes cell survival. The stress
      dependent miRNA miR-980 acts to buffer Rbfox1 levels, since it targets only those
      Rbfox1 transcripts that contain extended 3'UTRs. Reduced miR-980 expression
      during stress leads to increased Rbfox1 levels, widespread formation of various
      RNP granules, and increased cell viability. We show that human RBFOX proteins
      also contain multiple LCDs and form membraneless compartments, suggesting that
      the RNP granule-linked control of cellular adaptive responses may contribute to a
      wide range of RBFOX-associated pathologies in humans.

PMID- 29358751
TI  - Control of auxin-induced callus formation by bZIP59-LBD complex in Arabidopsis
      regeneration.
AB  - Induction of pluripotent cells termed callus by auxin represents a typical cell
      fate change required for plant in vitro regeneration; however, the molecular
      control of auxin-induced callus formation is largely elusive. We previously
      identified four Arabidopsis auxin-inducible Lateral Organ Boundaries Domain (LBD)
      transcription factors that govern callus formation. Here, we report that
      Arabidopsis basic region/leucine zipper motif 59 (AtbZIP59) transcription factor
      forms complexes with LBDs to direct auxin-induced callus formation. We show that
      auxin stabilizes AtbZIP59 and enhances its interaction with LBD, and that
      disruption of AtbZIP59 dampens auxin-induced callus formation whereas
      overexpression of AtbZIP59 triggers autonomous callus formation. AtbZIP59-LBD16
      directly targets a FAD-binding Berberine (FAD-BD) gene and promotes its
      transcription, which contributes to callus formation. These findings define the
      AtbZIP59-LBD complex as a critical regulator of auxin-induced cell fate change
      during callus formation, which provides a new insight into the molecular
      regulation of plant regeneration and possible developmental programs.

PMID- 29358749
TI  - Impaired Functional Criticality of Human Brain during Alzheimer's Disease
      Progression.
AB  - The progression of Alzheimer's Disease (AD) has been proposed to comprise three
      stages, subjective cognitive decline (SCD), mild cognitive impairment (MCI), and
      AD. Was brain dynamics across the three stages smooth? Was there a critical
      transition? How could we characterize and study functional criticality of human
      brain? Based on dynamical characteristics of critical transition from nonlinear
      dynamics, we proposed a vertex-wise Index of Functional Criticality (vIFC) of
      fMRI time series in this study. Using 42 SCD, 67 amnestic MCI (aMCI), 34 AD
      patients as well as their age-, sex-, years of education-matched 54 NC, our new
      method vIFC successfully detected significant patient-normal differences for SCD
      and aMCI, as well as significant negative correlates of vIFC in the right middle
      temporal gyrus with total scores of Montreal Cognitive Assessment (MoCA) in SCD.
      In comparison, standard deviation of fMRI time series only detected significant
      differences between AD patients and normal controls. As an index of functional
      criticality of human brain derived from nonlinear dynamics, vIFC could serve as a
      sensitive neuroimaging marker for future studies; considering much more vIFC
      impairments in aMCI compared to SCD and AD, our study indicated aMCI as a
      critical stage across AD progression.

PMID- 29358752
TI  - Citrus boom led to mafia.

PMID- 29358753
TI  - Pharmacogenetic stimulation of neuronal activity increases myelination in an axon
      specific manner.
AB  - Mounting evidence suggests that neuronal activity influences myelination,
      potentially allowing for experience-driven modulation of neural circuitry. The
      degree to which neuronal activity is capable of regulating myelination at the
      individual axon level is unclear. Here we demonstrate that stimulation of
      somatosensory axons in the mouse brain increases proliferation and
      differentiation of oligodendrocyte progenitor cells (OPCs) within the underlying
      white matter. Stimulated axons display an increased probability of being
      myelinated compared to neighboring non-stimulated axons, in addition to being
      ensheathed with thicker myelin. Conversely, attenuating neuronal firing reduces
      axonal myelination in a selective activity-dependent manner. Our findings reveal
      that the process of selecting axons for myelination is strongly influenced by the
      relative activity of individual axons within a population. These observed
      cellular changes are consistent with the emerging concept that adaptive
      myelination is a key mechanism for the fine-tuning of neuronal circuitry in the
      mammalian CNS.

PMID- 29358755
TI  - Maternal transmission disequilibrium of rs2248359 in type 2 diabetes mellitus
      families and its association with vitamin D level in offspring.
AB  - Association between T2DM and vitamin D deficiency has been reported in many
      epidemiologic studies. 24-hydroxylase encoded by CYP24A1 is the enzyme that
      degrades the active vitamin D metabolite. Variation in CYP24A1 may be associated
      with T2DM. This study investigates the association between rs2248359 in CYP24A1
      and T2DM by a family-based association test (FBAT) and in a case-control study.
      The FBAT results revealed that there was transmission disequilibrium for allele T
      in both additive model (Z = 2.041, P = 0.041227) and dominant model (Z = 2.722, P
      = 0.006496). Results of the case-control study suggested that rs2248359 may be a
      risk factor for female T2DM (P = 0.036) but not for male T2DM (P = 0.816).
      Furthermore, excessive transmission of allele T in T2DM offspring was observed
      compared with the non-T2DM offspring (OR 1.392; 95%CI 1.024-1.894; P = 0.035). In
      addition, combination of maternal CT and paternal CC genotypes had significant
      synergistic effect on obtaining CT genotype for offspring with T2DM (OR 6.245;
      95%CI 1.868-20.883; P = 0.004). Besides, lower level of 25(OH)D in T2DM offspring
      with genotype CT was observed as compared with the non-T2DM offspring (P =
      0.013). These data suggest that maternal transmission disequilibrium of allele T
      may be a risk factor for T2DM and vitamin D deficiency in T2DM offspring.

PMID- 29358756
TI  - Design of novel materials for additive manufacturing - Isotropic microstructure
      and high defect tolerance.
AB  - Electron Beam Melting (EBM) is a powder-bed additive manufacturing technology
      enabling the production of complex metallic parts with generally good mechanical
      properties. However, the performance of powder-bed based additively manufactured
      materials is governed by multiple factors that are difficult to control. Alloys
      that solidify in cubic crystal structures are usually affected by strong
      anisotropy due to the formation of columnar grains of preferred orientation.
      Moreover, processing induced defects and porosity detrimentally influence static
      and cyclic mechanical properties. The current study presents results on
      processing of a metastable austenitic CrMnNi steel by EBM. Due to multiple phase
      transformations induced by intrinsic heat-treatment in the layer-wise EBM process
      the material develops a fine-grained microstructure almost without a preferred
      crystallographic grain orientation. The deformation-induced phase transformation
      yields high damage tolerance and, thus, excellent mechanical properties less
      sensitive to process-induced inhomogeneities. Various scan strategies were
      applied to evaluate the width of an appropriate process window in terms of
      microstructure evolution, porosity and change of chemical composition.

PMID- 29358754
TI  - The nasal microbiome mirrors and potentially shapes olfactory function.
AB  - Olfactory function is a key sense for human well-being and health, with olfactory
      dysfunction having been linked to serious diseases. As the microbiome is involved
      in normal olfactory epithelium development, we explored the relationship between
      olfactory function (odor threshold, discrimination, identification) and nasal
      microbiome in 67 healthy volunteers. Twenty-eight subjects were found to have
      normal olfactory function, 29 had a particularly good sense of smell ("good
      normosmics") and 10 were hyposmic. Microbial community composition differed
      significantly between the three olfactory groups. In particular, butyric acid
      producing microorganisms were found to be associated with impaired olfactory
      function. We describe the first insights of the potential interplay between the
      olfactory epithelium microbial community and olfactory function, and suggest that
      the microbiome composition is able to mirror and potentially shape olfactory
      function by producing strong odor compounds.

PMID- 29358757
TI  - Validation and Comparison of a Model of the Effect of Sea-Level Rise on Coastal
      Wetlands.
AB  - Models are used to project coastal wetland distribution under future sea-level
      rise scenarios to assist decision-making. Model validation and comparison was
      used to investigate error and uncertainty in the Sea Level Affecting Marshes
      Model, a readily available model with minimal validation, particularly for
      wetlands beyond North America. Accurate parameterisation is required to improve
      the performance of the model, and indeed any spatial model. Consideration of
      tidal attenuation further enhances model performance, particularly for coastal
      wetlands located within estuaries along wave-dominated coastlines. The model does
      not simulate vegetation changes that are known to occur, particularly when
      sedimentation exceeds rates of sea-level rise resulting in shoreline
      progradation. Model performance was reasonable over decadal timescales,
      decreasing as the time-scale of retrospection increased due to compounding of
      errors. Comparison with other deterministic models showed reasonable agreement by
      2100. However, given the uncertainty of the future and the unpredictable nature
      of coastal wetlands, it is difficult to ascertain which model could be realistic
      enough to meet its intended purpose. Model validation and comparison are useful
      for assessing model efficacy and parameterisation, and should be applied before
      application of any spatially explicit model of coastal wetland response to sea
      level rise.

PMID- 29358758
TI  - Structural basis of AAUAAA polyadenylation signal recognition by the human CPSF
      complex.
AB  - Mammalian mRNA biogenesis requires specific recognition of a hexanucleotide
      AAUAAA motif in the polyadenylation signals (PAS) of precursor mRNA (pre-mRNA)
      transcripts by the cleavage and polyadenylation specificity factor (CPSF)
      complex. Here we present a 3.1-A-resolution cryo-EM structure of a core CPSF
      module bound to the PAS hexamer motif. The structure reveals the molecular
      interactions responsible for base-specific recognition, providing a rationale for
      mechanistic differences between mammalian and yeast 3' polyadenylation.

PMID- 29358760
TI  - Lithospheric folding by flexural slip in subduction zones as source for reverse
      fault intraslab earthquakes.
AB  - Subduction requires the permanent generation of a bend fold in the subducting
      slab which mechanics is not well understood. Lithospheric bending of subducting
      slabs was traditionally considered to be accommodated by orthogonal flexure,
      generating extensional outer rise earthquakes responsible of the external arc
      elongation during folding. Here we explore the possibility of lithospheric
      flexure being accommodated through simple shear deformation parallel to the slab
      (folding by flexural slip) and evaluate this process as source of earthquakes.
      The seismicity predicted by flexural slip dominated slab bending explains a
      significant amount of intermediate earthquakes observed in subduction zones with
      different degrees of coupling. This mechanism predicts the generation of
      intraslab thrust earthquakes with fault planes subparallel to the slab top. Being
      the orientations of the fault planes the same for the interface thrust
      earthquakes and the flexural-slip intraslab earthquakes, the amount of seismic
      moment liberated by the interface could be significantly lower than considered
      before. This proposed seismic source should be taken into account in models and
      hazard studies of subduction zones. Determining the seismic generating processes
      in subduction zones and their characteristics is a fundamental issue for the
      correct assessment of the associated seismic and tsunami risk.

PMID- 29358759
TI  - TRF1 participates in chromosome end protection by averting TRF2-dependent
      telomeric R loops.
AB  - The shelterin protein TRF2 assembles protective T loops at chromosome ends by
      stimulating intramolecular invasion of the telomeric G-rich single-stranded DNA
      (ssDNA) overhang into the duplex telomeric array. The other shelterin factor,
      TRF1, is thought to mainly facilitate telomeric dsDNA replication without
      directly participating in end protection. Here we show that in vitro human TRF2
      stimulates invasion of G-rich TERRA-like RNA into telomeric dsDNA, leading to
      formation of telomeric RNA-DNA hybrids (telR loops). The N-terminal basic domain
      of TRF2 binds to TERRA-like RNA and enables TRF2 to promote efficient RNA
      invasion. TRF1, through its N-terminal acidic domain, counteracts TRF2-mediated
      RNA invasion but not ssDNA invasion. In vivo, when TRF1 is depleted or replaced
      with a variant lacking the acidic domain, TRF2 induces formation of telR loops,
      which in turn cause telomere loss. Hence, uncontrolled TRF2 threatens telomere
      integrity, and TRF1 directly supports end protection by suppressing harmful telR
      loops.

PMID- 29358761
TI  - A gigantic marine ostracod (Crustacea: Myodocopa) trapped in mid-Cretaceous
      Burmese amber.
AB  - The mid-Cretaceous Burmese amber (~99 Ma, Myanmar), widely known for exquisite
      preservation of theropods, also yields microfossils, which can provide important
      contextual information on paleoenvironment and amber formation. We report the
      first Cretaceous ostracod in amber-the gigantic (12.9 mm) right valve of an
      exclusively marine group (Myodocopa: Myodocopida) preserved in Burmese amber.
      Ostracods are usually small (0.5-2 mm), with well-calcified carapaces that
      provide an excellent fossil record extending to at least the Ordovician (~485
      million years ago), but they are rarely encountered in amber. The new specimen
      effectively doubles the age of the ostracod amber record, offering the first
      representative of the Myodocopa, a weakly calcified group with a poor fossil
      record. Its carapace morphology is atypical and likely plesiomorphic. The
      preserved valve appears to be either a moulted exuvium or a dead and
      disarticulated specimen, and subsequent resin flows contain forest floor
      inclusions with terrestrial arthropods, i.e., fragmentary remains of spiders, and
      insect frass. These features resolve an enigmatic taphonomic pathway, and support
      a marginal marine setting for resin production.

PMID- 29358763
TI  - Science at the museum.

PMID- 29358762
TI  - Physical basis of specificity and delayed binding of a subtype selective sodium
      channel inhibitor.
AB  - Nerve and muscle signalling is controlled by voltage-gated sodium (Nav) channels
      which are the targets of local anesthetics, anti-epileptics and anti-arrythmics.
      Current medications do not selectively target specific types of Nav found in the
      body, but compounds that do so have the potential to be breakthrough treatments
      for chronic pain, epilepsy and other neuronal disorders. We use long computer
      simulations totaling more than 26 MUs to show how a promising lead compound can
      target one Nav implicated in pain perception and specific channels found in
      bacteria, and accurately predict the affinity of the compound to different
      channel types. Most importantly, we provide two explanations for the slow
      kinetics of this class of compound that limits their therapeutic utility.
      Firstly, the negative charge on the compound is essential for high affinity
      binding but is also responsible for energetic barriers that slow binding.
      Secondly, the compound has to undergo a conformational reorientation during the
      binding process. This knowledge aids the design of compounds affecting specific
      eukaryotic and bacterial channels and suggests routes for future drug
      development.

PMID- 29358764
TI  - Behind the art.

PMID- 29358766
TI  - Addendum: Plasmonic nanosensors with inverse sensitivity by means of enzyme
      guided crystal growth.
AB  - This corrects the article DOI: 10.1038/nmat3337.

PMID- 29358767
TI  - Corrigendum: Beating the thermodynamic limit with photo-activation of n-doping in
      organic semiconductors.
AB  - This corrects the article DOI: 10.1038/nmat5027.

PMID- 29358765
TI  - Organic solar cells based on non-fullerene acceptors.
AB  - Organic solar cells (OSCs) have been dominated by donor:acceptor blends based on
      fullerene acceptors for over two decades. This situation has changed recently,
      with non-fullerene (NF) OSCs developing very quickly. The power conversion
      efficiencies of NF OSCs have now reached a value of over 13%, which is higher
      than the best fullerene-based OSCs. NF acceptors show great tunability in
      absorption spectra and electron energy levels, providing a wide range of new
      opportunities. The coexistence of low voltage losses and high current generation
      indicates that new regimes of device physics and photophysics are reached in
      these systems. This Review highlights these opportunities made possible by NF
      acceptors, and also discuss the challenges facing the development of NF OSCs for
      practical applications.

PMID- 29358768
TI  - Materials science challenges in paintings.
AB  - Through the paintings of the old masters, we showcase how materials science today
      provides us with a vision of the processes involved in the creation of a work of
      art: the choice of materials, the painter's skill in handling these materials,
      and the perception of the finished work.

PMID- 29358769
TI  - Antimicrobials: Broad-spectrum antivirals.

PMID- 29358770
TI  - DNA nanostructures: Through, rather than across.

PMID- 29358771
TI  - Vaccine adjuvants: Softness makes it better.

PMID- 29358773
TI  - Material witness: All that glitters.

PMID- 29358772
TI  - Corrigendum: Plasmonic nanosensors with inverse sensitivity by means of enzyme
      guided crystal growth.
AB  - This corrects the article DOI: 10.1038/nmat3337.

PMID- 29358774
TI  - Retraction: Graded bandgap perovskite solar cells.
AB  - This corrects the article DOI: 10.1038/nmat4795.

PMID- 29358775
TI  - Targeting c-MET in gastrointestinal tumours: rationale, opportunities and
      challenges.
AB  - This corrects the article DOI: 10.1038/nrclinonc.2017.40.

PMID- 29358776
TI  - Prostate cancer: CTCs enable early prediction of response.

PMID- 29358777
TI  - Haematological cancer: Improved sensitivity in MRD detection.

PMID- 29358779
TI  - Colorectal cancer: Genomic landscape of mCRC revealed.

PMID- 29358781
TI  - Kidney cancer: PBRM1 loss promotes tumour response to immunotherapy.

PMID- 29358780
TI  - Gastrointestinal cancer: Novel promising first-line combination.

PMID- 29358782
TI  - [Incidence of type 1 diabetes in Navarre (2009-2016): higher in the southern
      regions of the autonomous community].
AB  - BACKGROUND: Geographical and seasonal variations of type 1 diabetes (T1D) are
      useful for establishing the key ethio-pathogenic factors of the disease. The
      present work seeks to analyze the incidence rates of T1D in Navarre for the 2009
      2016 period, its geographical distribution and seasonal variations in birth and
      diagnosis in affected persons. METHODS: Prospective study with one primary and
      three secondary sources. The completeness of the registry, determined using the
      capture-recapture method, was 96.08%. The confidence intervals of zone and onset
      season incidence rates were determined assuming an underlying Poisson
      distribution. Adjusted effect of onset age, sex, onset season and geographical
      area over changes in incidence rates were analyzed using a Poisson regression
      model. Comparison among areas was carried out after the corresponding adjustments
      of incidence by the indirect standardization method. RESULTS: Four hundred and
      twenty-eight new cases were detected (incidence= 8.36/100,000 inhabitants per
      year, CI95%: 7.58-9.19). The disease is predominant in males (63% of patients).
      The incidence in children under 15 years was higher than in adults (21.54, CI95%:
      18.43-25.02 vs. 5.94, CI95%: 5.23-6.71; p<0.001). Incidence was highest in the
      four southern regions of Navarre, most of the cases being in winter and spring.
      No differences were found regarding birth season over incidence. CONCLUSION:
      Navarre maintains a high T1D incidence in childhood that decreases progressively
      with age. Sex, age group, geographical zone and onset season are independently
      associated with the incidence rates observed in the study.

PMID- 29358778
TI  - Exogenous reproductive hormone use in breast cancer survivors and previvors.
AB  - Considerable controversy exists regarding the safety of elective exogenous
      hormonal exposure among breast cancer survivors and women at high risk of
      developing the disease (referred to herein as 'previvors'). We performed a
      qualitative analysis focused on four areas of potential exogenous exposure to
      hormones among previvors and survivors: hormonal contraception; systemic hormone
      replacement therapy (HRT); localized HRT; and hormonal manipulation for fertility
      preservation or enhancement. Herein, we discuss the available data and present
      clinical recommendations regarding the safety of hormonal exposure for both
      previvors and survivors. We found these data to be hampered by small cohort
      sizes, heterogeneous patient populations, and limited study designs, highlighting
      a great need to conduct further research with the aim of enabling better-informed
      patient management.

PMID- 29358783
TI  - Prostate cancer incidence and mortality in Navarre (Spain).
AB  - BACKGROUND: Prostate cancer is one of the most commonly diagnosed malignancies
      among males worldwide. In this study, overall and age-specific incidence and
      mortality trends are analyzed in order to present the past and current
      epidemiological situation of the disease in Navarre (Spain). METHODS: Population
      based incidence data from the 1975-2010 period, provided by the Cancer Registry
      of Navarre and prostate cancer specific mortality data for 1975-2013, provided by
      the Spanish Statistical Office, were used in the analysis. Age-standardized
      incidence and mortality rates, change-points and annual percentage changes (APC)
      were estimated by joinpoint regression analysis. One-dimensional P-spline models
      were used to estimate projections up to 2016. RESULTS: Considerable increases of
      cancer incidence rates in men aged 45-74 years were observed, with APC of +4.5%
      (p<0.001), +9.5% (p<0.001) and +2.4% (p<0.05) in the 1975-1990, 1990-2000 and
      2000-2010 periods, respectively. In the older than 74 age-group, an increase of
      incidence rates in the 1975-1999 period was registered (APC +3.3%, p<0.001),
      followed by a significant decrease up to 2010 (APC -4.0%, p<0.01). Mortality
      rates rose until 1995 (APC +2.2%, p<0.001) whereas a decline occurred afterwards
      up to 2013 (APC -3.4%, p<0.001). CONCLUSION: Even though overall prostate cancer
      incidence rates seem to have stabilized in 2002-2010 in Navarra, trends were
      different by age groups: increased in men 45-74 years old and decreased in the
      75+ year age-group. A decline in mortality rates was observed in both age groups
      since about 1995. Changes in the use of prostate specific antigen test for
      screening in oncoming years could affect future prostate cancer trends.

PMID- 29358784
TI  - [Uncomplicated urinary tract infections. Antimicrobial susceptibility study in
      Navarre].
AB  - BACKGROUND: Urinary tract infection (UTI) is a high prevalence infection at the
      community level. In order to improve the adequacy of the empirical therapy, we
      evaluated the etiology and the resistance pattern of the main uropathogens
      responsible for community acquired UTI in Navarre. METHODS: Retrospective study
      (2014-2016) in which we included microorganisms recovered with significant counts
      from samples of patients with community-acquired UTI. The global etiology and
      etiology according to age and sex was analyzed. Antimicrobial resistance was
      studied with urotopathogens isolated in 2016. RESULTS: Escherichia coli was the
      most frequently isolated microorganism both in the population (60.8%) and in each
      of the groups analyzed according to age and sex. The sensitivity of E. coli was:
      nitrofurantoin 97.4%, fosfomycin 96.5% amoxicillin-clavulanic acid 83.8%,
      trimethoprim-sulfamethoxazole 68.3%, quinolones 63.4% and amoxicillin 41.9%.
      Pooled sensitivity shows that the sensitivity to fosfomycin was 83.4% in men <15
      years, 89.4% in women <15 years and 81.9% in women between 15-65 years; and to
      nitrofurantoin was 86.7% in women <15 years and 82.2% in women between 15-65
      years. CONCLUSIONS: E. coli continues to be the most frequent microorganism in
      community-acquired UTI with a rate of sensitivity to fosfomycin and
      nitrofurantoin above 95%. The empirical treatment of UTI in our environment
      should not include amoxicillin, amoxicillin-clavulanic acid, trimethoprim
      sulfamethoxazole or quinolones. Fosfomycin may be empirically used in the
      treatment of uncomplicated cystitis in men younger than 15 years and in women
      under 65 years, and nitrofurantoin may be used empirically in women under 65
      years.

PMID- 29358785
TI  - [Opinions of Andalusian primary health care professionals].
AB  - BACKGROUND: The human papillomavirus (HPV) is the most common sexually
      transmitted disease, but its vaccination coverage is among the lowest in
      Andalusia. The aim of this study is to determine what primary health care
      professionals think and find out about the prevention of HPV infection among
      adolescents and the administration of the vaccine Method. Qualitative study using
      six focus groups with professionals from Primary Health Care in Seville, Granada
      and Jaen. Fourty-five professionals participated. An analysis of the semantic
      content was made, and answers were categorized in thematic units. RESULTS:
      Professionals recognize the difficulties in reaching the adolescent population
      concerning prevention of sexual risk behaviors, due to lack of time and little
      concern amongst adolescents about the preventive measures. Although the
      professionals recognize the symptoms of HPV infection, some did not know about
      the disease in men as well as the association with other cancers other than
      cervical cancer. They hesitate over whether to recommend the vaccine or not,
      leaving the decision to vaccinate their daughters in the hands of the parents.
      CONCLUSION: It would be advisable to establish strategies that improve the
      information that the professionals have about HPV as well as the benefits of the
      vaccine, so that they can transmit the benefits clearly and assertively to the
      parents. This would avoid parental uncertainty, improve vaccination rates, and
      decrease complications of infection (cancer).

PMID- 29358786
TI  - [Past and present of monitoring the functional immune response developed against
      Epstein-Barr and Adenovirus in hematopoietic stem cell transplantation].
AB  - Epstein-Barr (EBV) and Adenovirus (AdV) viral infections represent a significant
      cause of morbi-mortality in allogeneic hematopoietic stem cell transplantation
      recipients due to the use of immunomyelosuppressive treatments and the prolonged
      period of immunodeficiency that they generate. To date, the post-transplant
      protective role of EBV and AdV specific CD8+ T lymphocytes (CTLs) has been
      demonstrated. However, other factors are increasingly important in regulating the
      reconstitution and activity of CTLs specific to these viruses such as different
      cell subpopulations (CD4 + T lymphocytes, regulatory T lymphocytes, dendritic
      cells, Natural Killer cells, etc.), molecular mechanisms of immunoregulation and
      the drugs administered to the patient as prophylaxis for a possible graft-versus
      host disease. The aim of this review is to analyze the importance of monitoring
      the functional EBV and AdV-specific cellular response in the management of post
      transplant recipients.

PMID- 29358787
TI  - Risk factors for failure of continuous positive airway pressure treatment in
      patients with ostructive sleep apnoea.
AB  - BACKGROUND AND AIMS: Obstructive sleep apnoea is a potentially serious sleep
      disorder associated with the risk of cardiovascular disease. It is treated with
      continuous airway pressure (CPAP) but this is not always successful. Unsuccessful
      cases should be treated by bilevel positive airway pressure (BiPAP). The aim of
      this study was to determine whether common respiratory parameters and/or body
      mass index (BMI) can be used to predict the probability CPAP failure and hence
      start such patients on BiPAP from the outset. METHODS: A sample of patients
      treated by CPAP for OSAS was evaluated a retrospective cohort study. The data
      measured in sleep monitoring of the successfully treated group and of the group
      where CPAP had failed were compared. Subsequently, the predictive abilities of
      BMI, Apnoea Index (AI), Apnoea-Hypopnea Index (AHI), percentage of sleep time in
      less than 90% oxygen saturation (T90), average oxygen saturation over the
      duration of sleep (SaO2) and average desaturation per hour of sleep (ODI) were
      assessed with respect to CPAP failure, both individually and in combination.
      RESULTS: A sample of 479 patients was included in the study. All of the recorded
      variables except AI were significantly associated with failure of CPAP and their
      ability to predict the failure ranged from poor to moderate. Since there was
      significant correlation among all the variables measured a two-variable
      prediction model combining T90 and BMI produced no significant improvement in the
      quality of CPAP failure prediction. CONCLUSIONS: BMI was a significant predictor
      of CPAP failure although it was slightly less predictive than T90. The set of
      monitored variables included in our study does not allow for CPAP failure to be
      predicted with clinically relevant reliability.

PMID- 29358788
TI  - Irritable bowel syndrome - from etiopathogenesis to therapy.
AB  - Irritable bowel syndrome (IBS) is a chronic and relapsing functional
      gastrointestinal disorder that affects 9-23% of the population across the world.
      Patients with IBS are often referred to gastroenterology, undergo various
      investigations, take various medicines, take time off work and have a poor
      quality of life. The pathophysiology of IBS is not yet completely understood and
      seems to be multifactorial. Many pathogenetic factors, in various combinations,
      and not all necessarily present in each patient, can play an important role.
      Discomfort or abdominal pain relieived by defacation, asociated with a change in
      stool form, is a typical clinical manifestation of IBS. Many factors, such as
      emotional stress and eating, may exacerbate the symptoms. A timely diagnosis of
      IBS is important so that treatment which will provide adequate symptomatic relief
      (diarrhoea, constipation, pain and boaring) can be introduced. The diagnosis of
      IBS is not confirmed by a specific test or structural abnormality. It is made
      using criteria based on clinical symptoms such as Rome criteria, unless the
      symptoms are thought to be atypical. Today the Rome Criteria IV is the current
      gold-standard for the diagnoses of IBS. Treatment of patients with IBS requires a
      multidisciplinary approach. Some patients respond well to non-pharmacological
      treatment, while others also require pharmacological treatment. This review will
      provide a summary of pathophysiology, diagnostic criteria and therapies for IBS.

PMID- 29358789
TI  - Crohn's disease - genetic factors and progress of the disease.
AB  - BACKGROUND AND OBJECTIVES: Crohn's disease is a multifactorial inflammatory
      disease affecting mainly the gastrointestinal tract. The genetic factors that are
      involved in the disease include mainly three mutations of the gene NOD2/CARD15
      (R702W, G908R, 3020insC). The aim of this study was to determine the relationship
      between the presence of these variants and disease phenotype. MATERIAL AND
      METHODS: 70 patients with Crohn's disease were examined for the presence of the
      above-mentioned mutations. The researchers used the medical records to
      retrospectively obtain clinical data and together with the information obtained
      prospectively according to the protocol they analysed the connection between gene
      mutations and disease phenotype. RESULTS: At least one mutation was found in 22
      patients with Crohn's disease (32%), four patients were found to have two
      different mutations (composed heterozygotes - 6%) and six patients (9%) were
      homozygotes for the 3020insC gene. No significant differences were found between
      the groups with wild-type form and the mutated form of the NOD2 / CARD15 gene
      with respect to age at the time of diagnosis, form of the disease or localization
      according to the Montreal classification. CONCLUSION: Mutations of the NOD2 /
      CARD15 gene did not significantly affect the frequency of reoperations,
      homozygotes with 3020insC gene mutations, however, represented a high risk group.
      The phenotype was not related significantly to the presence of the examined
      mutations.

PMID- 29358790
TI  - Evaluation of microtextural properties of sourdough wheat bread obtained from
      optimized formulation using scanning electron microscopy and image analysis
      during shelf life.
AB  - The aim of this study was to evaluate the microtextural properties of optimized
      wheat bread formulation consisting sourdough (A) prepared with two different
      fermentation methods [spontaneous fermentation (F1) versus starter of lactic acid
      bacteria added fermentation (F2)], instant active dry yeast (B) and wheat bran
      (C) during shelf life. The optimized levels for F1 were 11.45 g 100 g-1 for
      sourdough, 1.10 g 100 g-1 for dry yeast and 1.58 g 100 g-1 for wheat bran and for
      F2 6.99 g 100 g-1 for sourdough, 1.02 g 100 g-1 for dry yeast and 38.84 g 100 g-1
      for wheat bran. The addition of sourdough significantly decreased the diameters
      of starch granules of sourdough breads, and affected shape and surface apparance
      of starch granules. The retrogradation phenomena during storage was explained
      with the change of interaction between starch granules and protein matrix. The F1
      fermentation method was found to be more effective in terms of bread textural
      properties examined.

PMID- 29358791
TI  - How well do plant based alternatives fare nutritionally compared to cow's milk?
AB  - Due to the issues like lactose intolerance and milk allergy arising from the
      consumption of cow's milk, there has been an increased demand in the plant based
      alternative milks around the world. Food industry has addressed these demands by
      introducing various milk beverages which are promoted as alternatives coming from
      plant sources which include almond milk and soy milk. Though they are popularly
      advertised as healthy and wholesome, little research has been done in
      understanding the nutritional implications of consuming these milk beverages in
      short term and long term. Further, consumers associate these alternatives to be a
      direct substitute of cow's milk which might not be true in all cases. This review
      tries to address the issue by outlining the differences between cow's milk and
      commercially available alternative milks in terms of their nutrient content.
      Though various plant based alternate milks have been studied, only the four most
      consumed milk beverages are presented in this review which are consumed widely
      around the world. A complete nutritional outline and the corresponding health
      benefits of consuming these plant based milk beverages have been discussed in
      detail which could help the consumers make an informed decision.

PMID- 29358792
TI  - Novel soybean-based high protein bar rich in isoflavones improves insulin
      sensitivity in diabetic Wistar rats.
AB  - This study assessed the effect of whey protein substitution with isolated soy
      protein in protein bar (PB) formulations at 25% (PB2), 50% (PB3), or 75% (PB1)
      weight/weight on the proximate and mineral composition, sensory, and antidiabetic
      properties. Sensory evaluation was conducted within diabetic (DB) and non
      diabetic (NDB) consumers by preference ranking and acceptance test. The
      formulations were analysed in terms of moisture, ash, protein, lipid,
      carbohydrates, fibers and mineral content. The consumers did not distinguish the
      formulations by preference ranking test. However, the acceptability test showed a
      rating of 9 most frequent for PB1 (36.30%), followed by PB2 and PB3 (both
      34.09%), among DB consumers. The PB1 and PB3 showed higher content of total,
      soluble and insoluble fibers and, PB 2 presented higher carbohydrate content.
      Potassium, sodium and calcium showed the highest mineral content in the
      formulations. PB3 was assessed for glycaemic and lipidemic control in diabetics
      and non-diabetics female Wistar rats, for this 20% of PB was added in the ration
      consumed ad libitum, besides, the rats received 100 mg/kg b. w. by gavage daily.
      The treatment did not reduce significantly fasting glucose, lipid profile, or
      peripheral glucose disposal in DB or NDB rats. However, it significantly improved
      insulin tolerance test values in diabetic rats. The results suggest that the
      formulations showed good acceptance and potentially ameliorate insulin resistance
      both in control group and in animal model of type II diabetes.

PMID- 29358793
TI  - Relationship between the firmness of Golden Delicious apples and the
      physicochemical characteristics of the fruits and their pectin during development
      and ripening.
AB  - Firmness at harvest determines the postharvest storability and quality of apples.
      The climate change has altered the physiological processes of fruits and the
      reliability of ripening indicators typically used to determine the harvest time,
      compromising fruit firmness. In this study, 'Golden Delicious' apples were
      harvested at several developmental/ripening stages (107, 122, 137, 152 and 167
      days after full bloom, DAFB) and evaluated for physicochemical attributes, which
      were correlated with fruit firmness. The 167 DAFB fruit corresponded to fruit at
      the commercial harvest. Fruit harvested at 107 and 122 DAFB did not develop the
      characteristics of ripe fruit while fruit harvested after 137 DAFB ripened
      normally. Fruit at commercial harvest showed low firmness. The changes of fruit
      weight, diameter, height, tristimulus color (L* values) as well as the content of
      total soluble solids and moisture in fruit correlated well with fruit firmness (r
      values from -0.76 to -0.97). The changes of pectin content, degree of
      esterification, molecular weight and content of glucose and galactose in pectin
      showed a positive relationship with firmness (r = 0.62-0.94). The content of
      protein, galacturonic acid and mineral elements in pectin correlated negatively
      with firmness (r -0.66 to -0.99). The results demonstrated that commercial
      harvest was delayed 30 days, compromising fruit firmness. Some underestimated
      ripening indicators may help in determining the harvest time of apples.

PMID- 29358794
TI  - Study of the proximate and mineral composition of different Nigerian yam chips,
      flakes and flours.
AB  - Yam (Dioscorea spp) is an essential tuber crop for hundreds of millions of people
      in many African, Asian and South American countries. Considering in particular
      Southwest Nigeria, chips, flakes and flours are amongst the most common shelf
      stable traditionally-processed yam products. This paper reports a systematic
      study on the proximate (moisture, protein, carbohydrate, fibre, fat, ash and
      gross energy) and mineral composition of these three food commodities sold in
      Nigerian markets. Results showed no significant differences in the moisture,
      crude protein and fibre content of all samples (10.0-12.3, 2.7-4.3 and 1.3-2.0
      wt%, respectively). Gross energy was also comparable for all yam derived food
      items (between 3300 and 3507 kcal/kg), contradicting the common belief that yam
      flakes have lower nutritional value than chips and flours. Considering the
      mineral composition, Ca, Mg, P and K were the predominant macronutrients.
      Micronutrients such as Zn, Co, Mn and Cu were also detected. Significant
      differences existed between products, and their various sources (markets).
      Principal component analysis showed a direct correlation between ash content of
      the samples and the assessed macronutrients, irrespective of the market, or the
      seller of the commodities. This study confirmed that yam derived food stuffs have
      an adequate nutritional composition, irrespective of their form and/or origin.

PMID- 29358795
TI  - Jabuticaba (Myrciaria jaboticaba) juice obtained by steam-extraction: phenolic
      compound profile, antioxidant capacity, microbiological stability, and sensory
      acceptability.
AB  - Jabuticaba (Myrciaria jaboticaba) is a dark-colored fruit native to Brazil that
      has a desirable flavor and high anthocyanin content. In the present study,
      jabuticaba juice was produced by steam-extraction and the phenolic compound
      profile, antioxidant capacity, instrumental color, and microbiological quality
      were evaluated during 90 days of storage at 25  degrees C. Cyanidin-3-O-glucoside
      represented 45% of the total phenolic content of the juice, which reduced with
      extent of 80% during storage. Total phenolic content of the juice increased by
      59% during 90 days of storage, which entailed, average 4.4-fold increase in the
      content of gallic and ellagic acids. FRAP assay was most sensitive for measuring
      gallic and ellagic acids, while the TEAC assay was the most sensitive for
      measuring anthocyanins. Although [Formula: see text] and [Formula: see text]
      values of jabuticaba juice decreased and [Formula: see text] increased during
      storage. Jabuticaba juice remained microbiologically stable during storage, and
      did not support the growth of inoculated Escherichia coli and Salmonella
      enteritidis, suggesting antimicrobial activity.

PMID- 29358796
TI  - Antimicrobial protection of minced pork meat with the use of Swamp Cranberry
      (Vaccinium oxycoccos L.) fruit and pomace extracts.
AB  - The objective of the study was to determine the antimicrobial activity of Swamp
      Cranberry (Vaccinium oxycoccos) fruit and pomace extracts (FSCE and PSCE) and
      their efficiency in minced pork meat. Ethanol (96 and 40%) and water were used
      for raw material extraction. Organic acids, flavonols, terpenes and stilbenes
      composition of the extracts was determined using HPLC. Minimal inhibitory
      concentration and minimum bactericidal/fungicidal concentration were determined
      for bacteria and fungi strains using the broth macrodilution method. The growth
      inhibition of Staphylococcus aureus, Listeria monocytogenes, Salmonella
      Enteritidis, and Escherichia coli in inoculated fresh minced pork meat containing
      2.5% we-PSCE or we-FSCE (prepared by using 40% ethanol) were evaluated within 6
      days of refrigeration storage. Swamp Cranberry pomace extracts contained
      stilbenes and more organics acids and flavonols than fruit extracts. Extracts
      inhibited Gram-positive bacteria strains stronger than Gram-negative, regardless
      of used raw material. The extracts did not show antifungal activity. Water
      ethanol extracts (we-FSCE and we-PSCE) had stronger antibacterial properties than
      ethanolic extracts (e-FSCE and e-PSCE) and aqueous extracts (w-FSCE and w-PSCE).
      A 2.5% addition of we-PSCE or we-FSCE to minced pork meat resulted in a reduction
      of the number of pathogenic cells by 4 log cycles after 4 days of refrigeration
      storage. Baked burgers containing 2.5% of these extracts obtained high ratings
      for color, taste, odor, juiciness, and overall acceptability that did not differ
      statistically from control samples. Extracts from Swamp Cranberry constitute
      interesting candidates for natural preservatives of minced pork meat.

PMID- 29358797
TI  - Assessment of chemical and sensory quality of sugarcane alcoholic fermented
      beverage.
AB  - This study aimed to verify the technological feasibility, chemical quality and
      sensory acceptance of alcoholic fermented beverage obtained from sugarcane juice.
      A completely randomized design was applied. Sugar and alcohol content, phenolic
      (HPLC-MS) and volatile (GS-MS) compounds, pH, density, dry matter and acidity of
      the fermented beverage of sugarcane were quantified, as well as the acceptance of
      the product was carried out. The complete fermentation of sugarcane lasted 7
      days, and it was obtained an alcohol content of 8.0% v/v. Titrable acidity of the
      beverage was of 67.31 meq L-1, pH 4.03, soluble solids of 5  degrees Brix,
      reducing sugar of 0.07 g glucose 100 g-1, density of 0.991 g cm-3, reduced dry
      matter of 14.15 g L-1, sulfates lower than 0.7 g K2SO4 L-1. Various phenolic
      compounds, among which, gallic acid (10.97%), catechin (1.73%), chlorogenic acid
      (3.52%), caffeic acid (1.49%), vanillic acid (0.28%), p-coumaric acid (0.24%),
      ferulic acid (6.63%), m-coumaric acid (0.36%), and o-coumaric acid (0.04%).
      Amongst aromatic compounds, were found mainly esters with fruity aromas (ethyl
      ester hexanoic acid and ethyl ester octanoic acid). The sugarcane juice can be
      commercialized as an alternative wine, as it presented adequate features to an
      alcoholic fermented beverage and was sensory accepted by consumers.

PMID- 29358798
TI  - A simple and fast method for discrimination of phage and antibiotic contaminants
      in raw milk by using Raman spectroscopy.
AB  - Phage and antibiotic in raw milk poses significant risks for starter culture
      activity in fermented products. Therefore, rapid detection of phage and
      antibiotic contaminations in raw milk is a crucial process in dairy science. For
      this purpose, a preliminary novel method for detection of phage and antibiotic
      was developed by using Raman spectroscopy. Streptococcus thermophilus phages and
      ampicillin which are quite important elements in dairy industry were used as
      model. The phage and antibiotic samples were added to raw milk separately, and
      Raman measurements were carried out. The obtained spectra were processed with a
      chemometric method. In this study, it has been demonstrated that the presence of
      phage has a titer sufficient to stop the fermentation (107 pfu/ml), and
      antibiotic in a concentration which inhibits the growth of starter cultures (0.5
      ug/ml) in raw milk could be discriminated through Raman spectroscopy with a short
      analysis time (30 min).

PMID- 29358799
TI  - Developing a vacuum cooking equipment prototype to produce strawberry jam and
      optimization of vacuum cooking conditions.
AB  - Purpose of this study was to develop prototype cooking equipment that can work at
      reduced pressure and to evaluate its performance for production of strawberry
      jam. The effect of vacuum cooking conditions on color soluble solid content,
      reducing sugars total sugars HMF and sensory properties were investigated. Also,
      the optimum vacuum cooking conditions for strawberry jam were optimized for
      Composite Rotatable Design. The optimum cooking temperature and time were
      determined targeting maximum soluble solid content and sensory attributes
      (consistency) and minimum Hue value and HMF content. The optimum vacuum cooking
      conditions determined were 74.4  degrees C temperature and 19.8 time. The soluble
      solid content strawberry jam made by vacuum process were similar to those
      prepared by traditional method. HMF contents of jams produced with vacuum cooking
      method were well within limit of standards.

PMID- 29358800
TI  - Effects of beta-glucan and resistant starch on wheat dough and prebiotic bread
      properties.
AB  - White wheat flour is a poor source of dietary fiber. Therefore a demand exists
      for enrichment of bread with non-digestible prebiotic ingredients that exert
      health-promoting effects. In this study, the effects of beta-glucan (BG) and
      resistant starch (RS) on the dough properties and bread-making characteristics
      were investigated. The water absorption of doughs increased with increasing BG
      and RS levels. Also, development time and farinograph quality number of BG
      enriched doughs remained similar to that of the control while the doughs
      stability decreased, and all of these values decreased when the RS was added. BG
      was more effective in increasing the dough softening than RS. The resistance to
      deformation, energy, maximum resistance and ratio number values; increased with
      the addition of RS or BG, but their extensibility was decreased in comparison to
      the control. Formulation containing BG/RS combination showed the best farinograph
      (development time, stability) and extensograph (resistance and extensibility)
      parameters. The application of BG and RS had similar effect on specific volume,
      and moisture content while it caused a decrease in firmness after 5 days of
      storage.

PMID- 29358801
TI  - Assessment of chemically characterised Gaultheria fragrantissima Wall. essential
      oil and its major component as safe plant based preservative for millets against
      fungal, aflatoxin contamination and lipid peroxidation during storage.
AB  - The present study aims survey of fungi causing deterioration of millets during
      storage, detection of aflatoxigenic fungal strains ans assessment of chemically
      characterized Gaultheria fragrantissiuma Wall essential oil (EO) and its major
      component methyl salicylate (MS) as plant based preservative. Essential oil (EO)
      and its major component methyl salicylate (MS) as plant based preservative was
      evaluated. In this study a total of 13 fungal species along with toxigenic strain
      of Aspergillus flavus were isolated from the millets. Chemical characterization
      of G. fragrantissima EO through GC-MS analysis revealed Methyl salicylate
      (98.04%) as major component. The EO significantly inhibited growth and aflatoxin
      B1 production by toxigenic strain of A. flavus LHP (B)-7 at 1.0 and 0.7 ul ml-1
      respectively. In addition, EO exhibited remarkable antioxidant activity (IC50 7.5
      ul ml-1). EO and MS showed non phytotoxic nature on germination of millets. The
      LD50 of the EO was 3833.33 ul kg-1 for mice showing favourable safety profile. In
      view of side effects of synthetic preservatives, the study recommends G.
      fragrantissima EO as a safe plant based preservative to enhance shelf-life of
      food commodities during storage.

PMID- 29358802
TI  - Effect of plant extracts on lipid and protein oxidation of mackerel (Scomber
      scombrus) mince during frozen storage.
AB  - The effects of different plant extracts [green tea extract (GTE), grape seed
      extract (GSE), and pomegranate rind extract (PRE)] at a level of 100 ppm
      equivalent phenolics and butylated hydroxytoluene (BHT) on the changes in quality
      of fish (Scomber scombrus) mince during 6 months frozen storage at -18 +/- 1 
      degrees C were investigated. During storage, significant oxidative reactions in
      both the lipids and proteins were observed with the increase in thiobarbituric
      acid reactive substances (TBARS) and carbonyls and decrease in sulphydryl groups
      and protein solubility. BHT and PRE effectively inhibited lipid oxidation as
      lower peroxide and TBARS values were observed. Moreover, antioxidants added to
      minced fish significantly reduced protein oxidation compared to control without
      any antioxidant. The minced fish containing PRE had lower carbonyl and higher
      sulphydryl contents, but no significant differences for carbonyl and sulphydry
      contents were observed among antioxidant sources. Protein solubility decreased
      with increase in storage period. The loss of protein solubility was higher in
      control samples than in antioxidant treated ones. Among antioxidant sources, PRE
      was an excellent antioxidant toward both lipid and protein oxidations. Therefore,
      it could be a potential source of natural antioxidants in minced fish during
      frozen storage.

PMID- 29358803
TI  - Production of egg white protein hydrolysates with improved antioxidant capacity
      in a continuous enzymatic membrane reactor: optimization of operating parameters
      by statistical design.
AB  - This study focuses on the influence of operating conditions on Alcalase-catalyzed
      egg white protein hydrolysis performed in a continuously stirred tank reactor
      coupled with ultrafiltration module (10 kDa). The permeate flow rate did not
      significantly affect the degree of hydrolysis (DH), but a significant increase in
      process productivity was apparent above flow rate of 1.9 cm3 min-1. By contrast,
      an increase in enzyme/substrate (E/S) ratio provided an increase in DH, but a
      negative correlation was observed between E/S ratio and productivity. The
      relationship between operating conditions and antioxidant properties of the
      hydrolysates, measured by three methods, was studied using Box-Behnken
      experimental design and response surface methodology. The statistical analysis
      showed that each variable (impeller speed, E/S ratio, and permeate flow rate) had
      a significant effect on the antioxidant capacity of all tested systems.
      Nevertheless, obtained response functions revealed that antioxidative activity
      measured by DPPH, ABTS and FRAP methods were affected differently by the same
      operating conditions. High impeller speeds and low permeate flow rates favor ABTS
      while high impeller speeds and high permeate flow rates had a positive effect on
      the DPPH scavenging activity. On the other hand, the best results obtained with
      FRAP method were achieved under moderate operating conditions. The integration of
      the reaction and ultrafiltration membrane separation in a continuous manner
      appears to be a right approach to improve and intensify the enzymatic process,
      enabling the production of peptides with desired antioxidant activity.

PMID- 29358804
TI  - Impact of pre-drying and frying time on physical properties and sensorial
      acceptability of fried potato chips.
AB  - In this work the effects of pre-drying and frying time on colour, oil, texture
      and sensorial acceptability (overall liking) of potato chips were evaluated.
      Potato chips were pre-dried for 0, 10, 20 and 30 min at 60  degrees C and fried
      in soybean oil at 190  degrees C for 60, 70 and 80 s. The colour parameters (L*,
      a* and b*) increased or decreased depending on the pre-drying and frying time.
      Hardness increased as the pre-drying and frying time increased. On the other
      hand, the water initially removed by pre-drying decrease the gradient of mass
      transfer (water-oil). The oil content reduced to (about 21%) in pre-dried samples
      when compared to control sample. Finally, sensorial evaluation showed that
      samples without pre-drying and/or fried for very short or very long times had low
      acceptance levels. The pre-drying and frying times influenced the colour,
      texture, water and oil content, and resulted into fried potato chips with better
      acceptance scores.

PMID- 29358805
TI  - Effect of carbon dioxide (CO2) and oxygen (O2) levels on quality of 'Palmer'
      mangoes under controlled atmosphere storage.
AB  - With the objective to evaluate the modifications in the fruit quality, 'Palmer'
      mangoes were stored at 12.8  degrees C for 30 days in controlled atmosphere
      storage that contained a low level of oxygen (5 kPa) which was associated with
      increasing levels of carbon dioxide CO2 (0, 1, 5, 10, 15 and 20 kPa CO2).
      Controlled atmosphere storage did not effect mango respiration. However, transfer
      mangoes, that were previously stored at high levels of CO2 (5 kPa O2 + 15 kPa CO2
      and 5 kPa O2 + 20 kPa CO2) to ambient temperature presented higher respiratory
      rates. No significant effects of increasing CO2 levels on color (L*,
      chromaticity, and hue angle), firmness, physical-chemical parameter and
      carbohydrate metabolism (total and reducing sugars, soluble pectin) were
      observed. After transfer to ambient temperature the mangoes ripened normally
      without any signs of CO2 injury. Therefore, the increment levels of CO2 neither
      improved the quality of the 'Palmer' mangoes nor presented a synergistic effect
      with low-oxygen when compared to 5 kPa O2-control.

PMID- 29358806
TI  - Effect of enzymatic pretreatment on the physical quality of plantain (Musa ssp.,
      group AAB) employing airflow reversal drying.
AB  - This work aimed to evaluate the effect of enzymatic pretreatment on the color and
      texture of plantain (Musa ssp., group AAB) dried by airflow reversal drying.
      Plantain slices 1.0 cm thick were used. Pretreatment with two commercial enzymes,
      Pectinex Ultra SPL (Aspergillus aculeatus) and Pectinex 3XL (Aspergillus niger),
      was performed. Drying kinetics were determined with and without pretreatment at
      temperatures of 50, 65 and 80  degrees C using a fixed bed convective dryer. An
      air speed of 6 m/s, a bed height of 5 cm and either unidirectional flow or
      airflow reversal (every 15 min) were used for drying. Color and texture were
      analyzed, and consumer acceptance of the results of the best treatments was
      determined. Pretreatment with the enzyme A. niger and airflow reversal gave the
      best drying kinetics and showed the greatest reduction in drying time (59.0%) at
      80  degrees C. The best hardness results were found at 80  degrees C with A.
      niger enzymatic pretreatment with both types of air flow. Brightness and hue
      angle showed that samples pretreated with enzymes and dried at 65  degrees C had
      a lighter yellow color compared to non-pretreated samples. Plantain samples
      enzymatically pretreated and dried at 65 and 80  degrees C were the most accepted
      by consumers. This kind of enzymatic pretreatment on plantain could allow the
      conservation of some physical properties and reduction of drying times relative
      to the current methodology.

PMID- 29358807
TI  - Characterization of baru nut (Dipteryx alata Vog) flour and its application in
      reduced-fat cupcakes.
AB  - Baru is a native specie from the Brazilian "cerrado" with interesting nutritional
      and sensory characteristics. The aim of our study was to characterize baru nut
      flour (BF) and to explore the possibility of producing reduced-fat baru cupcakes.
      Four different cupcake formulations were produced wheat flour (WF) containing 30%
      BF with reductions of 50 (F1), 75 (F2) and 100% (F3) margarine, compared to a
      control with 100% WF and 100% margarine (FC). BF showed 2.76% moisture, 19.2%
      proteins, 40.8% lipids, 3.05% ash and 18.51% dietary fiber. The substitution of
      wheat flour with 30% BF increased the mixing tolerance index and resistance to
      extension in the rheological analyses; however, these changes did not greatly
      influence cupcake quality. Firmness was the parameter most affected during shelf
      life, with statistically significant differences between the formulations. The
      cupcakes prepared with the blend of 70% WF + 30% BF and with fat reductions (F2
      and F3) can be considered "light", with the reduction of more than 30% margarine
      and a significant reduction of trans fatty acids. In the sensory analysis,
      formulation F2 obtained good acceptance scores.

PMID- 29358808
TI  - Study on the mobility of water and its correlation with the spoilage process of
      salmon (Salmo solar) stored at 0 and 4  degrees C by low-field nuclear magnetic
      resonance (LF NMR 1H).
AB  - Low-field nuclear magnetic resonance (LF NMR) was used to investigate the water
      mobility of salmon during cold storage and the correlation between texture,
      freshness, sensory quality and transversal relaxation times (T2) of salmon were
      studied. With the increasing of cold storage time, trapped water (T22), sensory,
      water holding capacity and cooking loss were descended while free water (T23),
      TVB-N and TBA were increased steadily, that reflected the quality of salmon
      quality visually. There was a significant correlation between sensory, hardness,
      TBA, cooking loss, K value and LF NMR parameters. The study showed that LF NMR
      was sensitive to different storage conditions which may be applied to monitor the
      quality of fish muscle, when the spoilage mechanism was affected by water
      properties and muscle structure.

PMID- 29358809
TI  - Effects of osmotic dehydration treatment on volatile compound (Myristicin)
      content and antioxidants property of nutmeg (Myristica fragrans) pericarp.
AB  - The effects of osmotic dehydration (OD) treatment on volatile compound
      (myristicin) content and the antioxidant capacity of nutmeg (Myristica fragrans)
      were studied. Fresh nutmeg pericarps were treated with varying sugar
      concentrations (60, 70, 80%) with different soaking periods at ambient
      temperature. The OD-treated nutmeg extracts were analyzed for myristicin content
      via Gas Chromatography Flame Ionization Detector. The phenolic content and
      antioxidant capacity were analyzed using Follin-Ciocalteu and a free radical
      scavenging activity assay. The myristicin content was highest (1.69 mg/100 mg) at
      80% sugar concentration after 3 h of soaking. Total phenolic content and free
      radical scavenging activity were highest at 3 h of 80% sugar solution treatment
      with values of 76.90% and 1.75 mg GAE/g, respectively. OD treatment at varying
      sugar concentration levels and durations affects the production of myristicin and
      antioxidant composition. Treatment of nutmeg with OD at 80% sugar concentration
      for 3 h is preferable, resulting in an acceptable level of myristicin and high
      antioxidants.

PMID- 29358810
TI  - The effect of drying temperatures on antioxidant activity, phenolic compounds,
      fatty acid composition and tocopherol contents in citrus seed and oils.
AB  - In this study, the effect of drying temperature on antioxidant activity, phenolic
      compounds, fatty acid composition and tocopherol content of citrus seeds and oils
      were studied. Kinnow mandarin seed, dried at 60  degrees C, exhibited the highest
      antioxidant activity. Orlendo orange seed had the maximum total phenolic content
      and alpha-tocopherol content, with a value of 63.349 mg/100 g and 28.085 mg/g
      (control samples), respectively. The antioxidant activity of Orlendo orange seed
      (63.349%) was higher than seeds of Eureka lemon (55.819%) and Kinnow mandarin
      (28.015%), while the highest total phenolic content was found in seeds of Kinnow
      mandarin, followed by Orlendo orange and Eureka lemon (113.132). 1.2
      Dihydroxybenzene (13.171), kaempferol (10.780), (+)-catechin (9.341) and
      isorhamnetin (7.592) in mg/100 g were the major phenolic compounds found in
      Kinnow mandarin. Among the unsaturated fatty acids, linoleic acid was the most
      abundant acid in all oils, which varied from 44.4% (dried at 80  degrees C) to
      46.1% (dried at 70  degrees C), from 39.0% (dried at 60  degrees C) to 40.0%
      (dried at 70  degrees C). The total phenolic content, antioxidant activity and
      phenolic compounds of citrus seeds and tocopherol content of seed oils were
      significantly affected by drying process and varied depending on the drying
      temperature.

PMID- 29358812
TI  - Characterizing genotypic variation in biochemical composition, anti-nutritional
      and mineral bioavailability of some Nigerian yam (Dioscorea spp.) land races.
AB  - The aim of this study was to characterize 43 genotypes from five yam species
      [Dioscorea rotundata (Poir), Dioscorea alata (Linn), Dioscorea bulbifera (Linn),
      Dioscorea cayenensis (Lam) and Dioscorea dumetorum (Kunith) Pax] which are major
      land races in Nigeria in terms of their chemical composition, nutritional, anti
      nutritional and mineral bioavailability. Findings showed that there was genotypic
      variation in terms of chemical composition, mineral profile and bioavailability
      of the minerals among the germplasm. D. bulbifera had the highest cell wall
      carbohydrates, (cellulose: 3.2%, hemicelluloses, 2.1%, lignin, 1.1%, acid
      detergent fibre (ADF) 3.2%, neutral detergent fibre (NDF) 6.4%), D. rotundata had
      the highest oxalate (606 mg/kg). In conclusion, intra and inter-species
      variations exist among the yam germplasm in terms of their chemical composition,
      anti-nutritional and mineral bioavailability. Phytate content of the yam
      genotypes did not affect the bioavailability of Zn but Ca was affected
      significantly. The Ox:Ca ratio in most of the yam varieties were below one, thus
      bioavailability of Ca in yam by oxalate is variety dependent.

PMID- 29358811
TI  - A rapid and sensitive evaluation of nitrite content in Saudi Arabian processed
      meat and poultry using a novel ultra performance liquid chromatography-mass
      spectrometry method.
AB  - Quantitative assessment of nitrite (NO2-) anion was performed using a newly
      developed high throughput ultra performance liquid chromatography-mass
      spectrometric (UPLC-MS) method. The nitrite determination with the proposed
      method using micellar mobile phase was unknown. Selected ion reaction mode using
      negative electrospray ionization was adopted for the identification and
      quantitative analysis of nitrite. The chromatographic separation was performed
      using BEH C-18 column and a micellar mobile phase consisted of sodium dodecyl
      sulphate and acetonitrile in ratio 30:70 was used. The elution of nitrite anion
      was accomplished in less than 1 min. Under the optimal analysis conditions, the
      linearity of the developed method was checked in the concentration range of 0.5
      20 mg kg-1 NO2- with an excellent correlation coefficient of 0.996. The
      precisions of the method with relative standard deviation <2% was observed when
      standard at concentration of 1 mg kg-1 was used. The limit of detection and limit
      of quantitation of the developed mass spectrometric method was found to be 0.114
      and 0.346 mg kg-1, respectively. The developed UPLC/MS method was applied to
      quantify this anion in processed meats and poultries from various super market of
      Saudi Arabia (Riyadh region). The recoveries of the nitrite in the various
      samples were found in the range of 100.03-103.5%.

PMID- 29358814
TI  - Effect of malt process steps on bioactive properties and fatty acid composition
      of barley, green malt and malt grains.
AB  - In this study, the effect of barley malt process on antioxidant activity,
      carotenoid content, oil yield, phenolic compounds and fatty acid composition of
      barley, green malt and malt was investigated. The highest antioxidant activity
      (79.80%) and total phenolic content (122.43 mg/100 g) was observed in green malt.
      Carotenoid content of green malt (1.71 ug/g) was higher than those of barley and
      malt. Green malt had the maximum (+)-catechin (69.06 mg/100 g), 1,2
      dihydroxybenzene (37.21 mg/100 g), quercetin (30.78 mg/100 g) and isorhamnetin
      (22.44 mg/100 g) content. Oil contents of samples ranged from 1.73 to 2.13% and
      showed increase with malting process. While barley lipids contained 18.53%
      palmitic, 19.94% oleic and 51.74% linoleic acids, malt oil contained 17.33%
      palmitic, 15.62% oleic and 56.56% linoleic acids. Linoleic acid content increased
      during malting process while oleic and palmitic acid content decreased.

PMID- 29358813
TI  - Study on the spoilage potential of Pseudomonas fluorescens on salmon stored at
      different temperatures.
AB  - The bacterial kinetics and quality indexes [sensory quality, total volatile basic
      nitrogen (TVB-N), thiobarbituric acid value, biogenic amine, and amino acids]
      were analyzed on salmon inoculated with Pseudomonas fluorescens during storage
      under different temperatures (30, 10, and 4  degrees C). The bacterial kinetics
      revealed that P. fluorescens showed a steady growth at low temperatures (10 and 4
      degrees C). The TVB-N yield factors of the sample stored at 4  degrees C
      indicated that each bacterial cell of P. fluorescens displayed greater spoilage
      activity at low temperatures. A remarkable correlation was found between the
      production of biogenic amines and bacterial counts. The results also highlighted
      that P. fluorescens cultured at 4  degrees C had higher demand for amino acids.

PMID- 29358815
TI  - Modelling postmortem evolution of pH in beef M. biceps femoris under two
      different cooling regimes.
AB  - A model based on enzyme kinetics was developed to predict differences in
      postmortem pH change in beef muscles as affected by cooling rate. For the
      calibration and validation of the model, pH and temperature measurements were
      conducted at different positions in M. biceps femoris following conventional
      carcass cooling or faster cooling of the muscle after hot boning. The glycogen
      conversion, and, hence, the pH fall, was observed to significantly vary with
      position and cooling regime but only during the initial hours of cooling.
      Comparison of the cooling regimes indicated that fast cooling following hot
      boning avoids heat shortening induced by the combined effect of high temperature
      and low pH.

PMID- 29358816
TI  - Stabilities of tocopherols and phenolic compounds in virgin olive oil during
      thermal oxidation.
AB  - The effects of thermal oxidation at 60  degrees C on tocopherols (alpha, beta,
      gamma) and phenolic compounds (hydroxytyrosol and tyrosol) of olive oil were
      studied. Tocopherols were determined by HPLC and phenolic compounds by HPLC and
      GC-MS. Peroxide value of olive oil increased with treatment time until it reached
      to 56.6 meq/kg. alpha-Tocopherol, beta-tocopherol and gamma-tocopherol contents
      of olive oil decreased with treatment time. alpha-Tocopherol in olive oil was
      decomposed after 63 days of treatment. beta-Tocopherol in olive oil was depleted
      after 33 days of treatment. The reduction in gamma-tocopherol of olive oil was
      75% after 63 days of treatment. The degradation of hydroxytyrosol in olive oil
      was 91% after 63 days of treatment. Tyrosol was more stable than hydroxytyrosol
      in olive oil. Inverse correlations of peroxide value with hydroxytyrosol, alpha
      Tocopherol, beta-tocopherol and gamma-tocopherol were observed.

PMID- 29358817
TI  - Some probiotic characteristics of a fermented milk product based on microbiota of
      "Tibetan kefir grains" cultivated in Ukrainian household.
AB  - The article describes some probiotic properties of fermented product made of
      natural association of Tibetan kefir grains cultivated in Ukrainian household
      (UTKG); also, the effect of UTKG microbiota on the growth of pathogenic
      microbiota and sensitivity to antibiotics was studied. It was found that the test
      cultures of oppurtunistic pathogens (Staphylococcus aureus, Bacillus
      mesentericus, and Mycobacterium luteum) were sensitive; bacteriostatic zone of
      the test-culture ranged from 21 to 25 mm, and highly sensitive (Proteus vulgaris
      and Aspergillus niger) bacteriostatic zone exceeded 25 mm to probiotic bacteria
      of fermented product. UTKG microbiota is also moderately sensitive to multiple
      antibiotics that allows defining the obtained fermented milk product as
      functional with therapeutic properties. During the study of the influence of
      different NaCl and bile concentrations on acid-activity of UTKG it was found that
      active acid formation occurred at the concentrations up to 4% NaCl in cultivation
      medium (boiled milk) and at 20% bile and 0.45% phenol. It proves microbial
      association to be capable of withstanding adverse gastrointestinal conditions and
      continue developing.

PMID- 29358819
TI  - Volatile flavour compounds, sensory characteristics and antioxidant activities of
      mungbean meal protein hydrolysed by bromelain.
AB  - Enzymatic mungbean meal protein hydrolysate (eb-MPH) is a novel natural
      flavour/antioxidant source. A 15% bromelain (w/w) concentration with a hydrolysis
      time of 12 h was the optimum conditions to produce eb-MPH, which showed the
      greatest antioxidant activities and sensory characteristics. eb-MPH was composed
      of oligopeptides that had low molecular weight (< 10 kDa) as well as surface
      hydrophobicity and high content of hydrophobic amino acids. eb-MPH contributed to
      DPPH (80) and ABTS (95%) scavenging activities and to savoury/sweet flavour
      volatile compounds (3-methyl-butanal, furfural and benzaldehyde), bouillon odour,
      sweet odour, chicken odour, meaty odour, moderate bitter taste and umami. In
      addition, principal component analysis (PCA) showed that 72.87% of the total
      variance confirmed the correlation between DH, S0, DPPH, ABTS, sensory
      characteristics and volatile flavour compounds. These results suggested that eb
      MPH can be used as a natural food flavouring agent and antioxidant.

PMID- 29358818
TI  - Inactivation model and risk-analysis design for apple juice processing by high
      pressure CO2.
AB  - Sigmoidal microbial survival curves are observed in high-pressure carbon dioxide
      (HPCD) pasteurization treatments. The objectives of this study were to use the
      Gompertz primary model to describe the inactivation in apple juice of the
      pathogen Escherichia coli CGMCC1.90 and to apply probabilistic engineering to
      select HPCD treatments meeting at least 5 log10 reductions (SV >= 5) at 95%
      confidence. This required secondary models for the temperature (T,  degrees C)
      and pressure (P, MPa) dependence of the Gompertz model parameters. The
      expressions [Formula: see text] and [Formula: see text] selected using goodness
      of-fit measures and assessments based on Akaike and Bayesian information criteria
      were consistent with proposed mechanistic models for HPCD bactericidal effects.
      Monte Carlo simulations accounting for the variability and uncertainty of the
      parameter b and c estimates were used to predict SV values for a given time,
      temperature and CO2 pressure combination and desired confidence boundary. A
      similar approach used to estimate process times meeting SV >= 5 at 95% confidence
      for a given temperature and CO2 pressure combination, showed that HPCD processes
      met this requirement only for relatively long processing times, i.e., 35-124 min
      in the experimental range of 32-42  degrees C and 10-30 MPa. Therefore, further
      HPCD research is required to reduce processing time.

PMID- 29358820
TI  - Characterization of starch-based bioplastics from jackfruit seed plasticized with
      glycerol.
AB  - Biodegradable films based on starches from different botanical sources exhibited
      physicochemical and functional properties which were related with the starch
      characteristics. However, had inadequate mechanical properties and were hard and
      brittle. In this research, jackfruit seed starch plasticized with glycerol were
      developed and characterized. The starch and glycerol concentrations ranged from 2
      to 6% w/w and 20 to 60 g/100 g starch, respectively. Bioplastics were obtained by
      the casting method and characterized in terms of color, mechanical properties,
      solubility, water vapor permeability (WVP), morphology and free energy of the
      hydrophobic interaction. Electronic micrographics showed the presence of some
      intact starch granules. The bioplastics were hydrophilic and those of 6% starch
      and 40% glycerol were the most hydrophilic ([Formula: see text] = 41.35 mJ m-1).
      The solubility of the films presented a direct relationship with the starch
      concentration ranging from 16.42 to 23.26%. Increased opacity and color
      difference were observed with increasing starch concentration. The WVP ranged
      from 1.374 * 10-3 to 3.07 * 10-4 g m/day m2 which was positively related with the
      concentration of starch and glycerol. Tensile strength, percent elongation and
      Young's Modulus indicated that the jackfruit starch and glycerol provided a film
      with good mechanical properties. The results replaced that jackfruit starch can
      be used to develop films, with low opacity, moderate WVP and relatively high
      mechanical stability, by using glycerol in the gelatinized starch dispersions.

PMID- 29358821
TI  - Production and characterization of nanostructured lipid carriers and solid lipid
      nanoparticles containing lycopene for food fortification.
AB  - In this study, lycopene, was loaded on nanostructured lipid carrier and solid
      lipid nanoparticles using combination of high shear homogenization and
      ultrasonication method. Effect of applied lipids types, nanocarrier's type and
      lycopene loading on physicochemical properties of developed nanocarriers were
      studied. Particle sizes of developed nanocarriers were between 74.93 and 183.40
      nm. Encapsulation efficiency of nanostructured lipid carrier was significantly
      higher than solid lipid nanoparticles. Morphological study of developed
      nanocarriers using scanning electron microscopy showed spherical nanoparticles
      with smooth surface. Lycopene was entrapped in nanocarriers without any chemical
      interaction with coating material according to Fourier transform infrared
      spectroscopy spectrum and differential scanning calorimetry thermogram. Glycerol
      monostearate containing nanoparticles showed phase separation after 30 days in 6
      and 25  degrees C, whereas this event was not observed in nanosuspensions that
      produced by glycerol distearate. Lycopene release in gastrointestinal condition
      was studied by the dialysis bag method. To evaluate nanocarrier's potential for
      food fortification, developed lycopene-loaded nanocarriers were added to orange
      drink. Results of sensory analysis indicated that nanoencapsulation could obviate
      the poor solubility and tomato after taste of lycopene. Fortified sample with
      lycopene nanocarriers didn't show significant difference with blank orange drink
      sample except in orange odor.

PMID- 29358822
TI  - Seasonal variations of Saanen goat milk composition and the impact of climatic
      conditions.
AB  - The aim of this research was to investigate the effect of climatic conditions and
      their impact on seasonal variations of physico-chemical characteristics of Saanen
      goat milk produced over a period of 4 years. Lactation period (early, mid and
      late) and year were considered as factors that influence physico-chemical
      composition of milk. Pearson's coefficient of correlation was calculated between
      the physico-chemical characteristics of milk (fat, proteins, lactose, non-fat dry
      matter, density, freezing point, pH, titrable acidity) and climatic condition
      parameters (air temperature, temperature humidity index-THI, solar radiation
      duration, relative humidity). Results showed that all physico-chemical
      characteristics of Saanen goat milk varied significantly throughout the lactation
      period and years. The decrease of fat, protein, non-fat dry matter and lactose
      content in goat milk during the mid-lactation period was more pronounced than was
      previously reported in the literature. The highest values for these
      characteristics were recorded in the late lactation period. Observed variations
      were explained by negative correlation between THI and the physico-chemical
      characteristics of Saanen goat milk. This indicated that Saanen goats were very
      prone to heat stress, which implied the decrease of physico-chemical
      characteristics during hot summers.

PMID- 29358823
TI  - Caco-2 cell transport of purple sweet potato anthocyanins-phospholipids complex.
AB  - In this study, the role of phospholipids in transepithelial transport and the
      impact on the antioxidant activity of purple sweet potato anthocyanins (PSPAs)
      was evaluated. PSPAs were purified by column chromatography, and then PSPAs
      phospholipids complex (PSPAs-PC) was prepared. In antioxidant assay in vitro,
      PSPAs-PC exhibited potential antioxidant activity; meanwhile, it exhibited
      relatively higher stability in mimic gastrointestinal digestion conditions. The
      inhibitory effect of PSPAs-PC on the oxidation of soybean oil was significantly
      higher after 15 days storage. The presence of phospholipids increased the
      transepithelial transport of PSPAs; its apparent permeability coefficient (Papp)
      was higher, while its efflux ratio was lower than PSPAs. Based on the above
      results, it clearly displays the potential of phospholipids in the promotion of
      intestinal transport of PSPAs, and further studies are needed to explore the in
      depth mechanism of the bioavailability promotion effect of phospholipids.

PMID- 29358824
TI  - Purification and characterization of acid phosphatase from Macrotyloma uiflorum
      seeds.
AB  - Acid phosphatases play a crucial role in food processing industries to reduce
      phosphate content of food. Here in acid phosphatase from the seeds of Macrotyloma
      uniflorum has been purified to homogeneity using UNOsphere-S cation exchange
      chromatography followed by gel filtration with 81.85 fold purification. Molecular
      weight of purified enzyme was 55,000 (+/- 1040) Daltons under physiological
      conditions. It was a heterodimer of subunits having molecular weights 27,093 and
      28,241 Daltons as determined by MALDI-TOF analysis. The optimum pH and
      temperature for the purified enzyme was 5.0 and 50  degrees C respectively. The
      enzyme was stable in the pH range 3.5-5.5 and showed temperature stability up to
      60  degrees C. Substrate specificity of enzyme was checked with different
      substrates namely, p-nitrophenyl phosphate (p-NPP), ATP, ADP, glucose 6
      phosphate, glucose-1-phosphate, fructose 6-phosphate, phenyl phosphate, alpha
      naphthyl-phosphate, pyridoxyl phosphate and beta-glycerophosphate. Enzyme showed
      high substrate specificity towards p-NPP, phenyl phosphate, ATP and alpha
      naphthyl phosphate. Km and Vmax of enzyme were found to be 0.934 mM and 1.333
      mM/min respectively with respect to p-NPP as a substrate. Chemical modification
      studies showed that tryptophan was present at the active site of the enzyme.

PMID- 29358825
TI  - Effects of fatty acids composition and microstructure properties of fats and oils
      on textural properties of dough and cookie quality.
AB  - This study was carried out to investigate the effect of fatty acid composition
      and microstructure properties of fats and oils on the textural properties of
      cookie dough and quality attributes of cookies. Fatty acid composition and
      microstructure properties of six fats and oils (butter, hydrogenated fat, palm
      oil, coconut oil, groundnut oil, and sunflower oil) were analyzed. Sunflower oil
      was found to be the most unsaturated oil with 88.39% unsaturated fatty acid
      content. Coconut oil and palm oil differed from other fats and oils by having an
      appreciable amount of lauric acid (59.36%) and palmitic acid (42.14%),
      respectively. Microstructure size of all fats and oils ranged from 1 to 20 MUm
      being the largest for coconut oil and the smallest for palm oil. In palm oil,
      small rod-shaped and randomly arranged microstructures were observed, whereas
      sunflower oil and groundnut oil possessed large, scattered ovule shaped
      microstructures. It was reported that sunflower oil produced the softest dough,
      the largest cookie spread and the hardest cookie texture, whereas hydrogenated
      fat produced the stiffest dough, the lowest spread and most tender cookies.
      Statistical analysis depicted that palmitic acid and oleic acid demonstrated a
      positive correlation with dough hardness. Linoleic acid exhibited positive link
      with cookie spread ratio (r = 0.836**) and breaking strength (r = 0.792**).
      Microstructure size showed a significant positive relationship with dough density
      (r = 0.792**), cookie density (r = 0.386*), spread ratio (r = 0.312*), and
      breaking strength (r = 0.303*).

PMID- 29358826
TI  - Co-production of functional exopolysaccharides and lactic acid by Lactobacillus
      kefiranofaciens originated from fermented milk, kefir.
AB  - Kefiran is a functional exopolysaccharide produced by Lactobacillus
      kefiranofaciens originated from kefir, traditional fermented milk in the
      Caucasian Mountains, Russia. Kefiran is attractive as thickeners, stabilizers,
      emulsifiers, gelling agents and also has antimicrobial and antitumor activity.
      However, the production costs of kefiran are still high mainly due to high cost
      of carbon and nitrogen sources. This study aimed to produce kefiran and its co
      product, lactic acid, from low-cost industrial byproducts. Among the sources
      tested, whey lactose (at 2% sugar concentration) and spent yeast cells
      hydrolysate (at 6 g-nitrogen/L) gave the highest kefiran of 480 +/- 21 mg/L along
      with lactic acid of 20.1 +/- 0.2 g/L. The combination of these two sources and
      initial pH were optimized through Response Surface Methodology. With the
      optimized medium, L. kefiranofaciens produced more kefiran and lactic acid up to
      635 +/- 7 mg/L and 32.9 +/- 0.7 g/L, respectively. When the pH was controlled to
      alleviate the inhibition from acidic pH, L. kefiranofaciens could consume all
      sugars and produced kefiran and lactic acid up to 1693 +/- 29 mg/L and 87.49 +/-
      0.23 g/L, respectively. Moreover, the fed-batch fermentation with intermittent
      adding of whey lactose improved kefiran and lactic acid productions up to 2514 +/
      93 mg/L and 135 +/- 1.75 g/L, respectively. These results indicate the promising
      approach to economically produce kefiran and lactic acid from low-cost nutrient
      sources.

PMID- 29358827
TI  - Phytochemical composition, antioxidant and anti-bacterial activity of Syzygium
      calophyllifolium Walp. fruit.
AB  - Syzygium calophyllifolium fruits are among the important wild edibles used by the
      tribes of Western Ghats. However, this underutilized fruit remained unnoticed for
      its medicinal properties. Hence, the present study was undertaken to evaluate the
      antioxidant activity by DPPH., ABTS.+, FRAP assays and antibacterial efficacy by
      well diffusion method. GC-MS and HPLC profiles of crude extract and column
      chromatographic fractions were also determined. The methanolic extract of fruit
      (MFE) showed high total phenolics, tannins and flavonoids. The faction H (FH)
      displayed significant antioxidant property in DPPH. (IC50 2.1 ug/ml), ABTS.+
      (19483.29 MUM Trolox equivalents/g extract) and FRAP (65.5 mM Fe(II)/mg extract)
      assays over MFE. Moreover, FH also exhibited good antibacterial activity against
      Escherichia coli (32.0 mm), Salmonella typhi (27.0 mm), Staphylococcus aureus
      (27.3 mm) at 100 mg/ml concentration. GC-MS revealed 12 major compounds in MFE,
      HPLC analysis of MFE and FH depicted the presence of rutin and ellagic acid. This
      study suggested that FH could have high concentration of bioactive compounds like
      rutin and ellagic acid or its analogues compared to MFE which may be responsible
      for its strong antioxidant and antibacterial activity.

PMID- 29358828
TI  - Individual shrink wrapping extends the storage life and maintains the quality of
      pomegranates (cvs. 'Mridula' and 'Bhagwa') at ambient and low temperature.
AB  - The present investigation was carried out to study the response of two commercial
      pomegranate cultivars to individual shrink wrapping in extending the storage life
      and quality maintenance. Pomegranate fruits ('Mridula' and 'Bhagwa') were
      individually shrink wrapped using three semi-permeable films (Cryovac(r) BDF
      2001, D-955 and normal LDPE) and stored at ambient (25-32  degrees C and 49-67%
      RH) and low temperature (8  degrees C and 75-80% RH). Shrink wrapping greatly
      reduced weight loss in both cultivars irrespective of the film used and storage
      temperature. Weight loss in shrink wrapped (D-955 film) 'Mridula' and 'Bhagwa'
      after 1 month storage at ambient temperature was respectively 1.40 and 1.05%,
      when compared to 22.92 and 22.53% in non-wrapped fruits. After 3 months at 8 
      degrees C, shrink wrapped 'Mridula' and 'Bhagwa' fruits lost only 0.43 and 0.68%
      weight respectively, compared to 17.23 and 21.67% in non-wrapped ones. Shrink
      wrapping significantly reduced the respiration rate at ambient temperature and
      the response varied with variety and film used. Shrink wrapped fruits of both
      cultivars retained the original peel colour (Hunter h? and C* values) to a
      maximum extent during 3 months storage at 8  degrees C and shelf-life period at
      ambient temperature. Irrespective of variety and film, shrink wrapping maintained
      the peel thickness and peel moisture content, significantly much higher than non
      wrapped fruits at both temperatures. Compared to 'Mridula' cultivar, 'Bhagwa'
      responded well to shrink wrapping during prolonged storage at both temperatures
      with better maintenance of quality in terms of appearance, colour, juice content,
      TSS, acidity, sugars and sensory attributes. At ambient temperature, shrink
      wrapping with D-955 or LDPE film extended the storage life of 'Mridula' and
      'Bhagwa' for 3 weeks and 1 month respectively, whereas at 8  degrees C both could
      be stored for 3 months with 3 days of shelf life.

PMID- 29358830
TI  - The effect of heat treatment on phenolic compounds and fatty acid composition of
      Brazilian nut and hazelnut.
AB  - Brazilian peanut oil content increased with oven heating (65.08%) and decreased
      with microwave heating process (61.00%). While the phenolic content of untreated
      Brazilian nut was the highest of 68.97 mg GAE/100 g. Hazelnut (Sivri) contained
      the highest antioxidant activity (86.52%, untreated). Results reflected
      significantly differences between the antioxidant effect and total phenol
      contents of Brazilian nut and hazelnut (Sivri) kernels heated in the oven and
      microwave. Microwave heating caused a decrease in antioxidant activity of
      hazelnut. Gallic acid, 3,4-dihydroxybenzoic acid and (+)- and catechin were the
      main phenolic compounds of raw Brazilian nut with the value of 5.33, 4.33 and
      4.88 mg/100 g, respectively, while the dominant phenolics of raw hazelnut (Sivri)
      kernels were gallic acid (4.81 mg/100 g), 3,4-dihydroxybenzoic acid (4.61 mg/100
      g), (+)-catechin (6.96 mg/100 g) and 1,2-dihydroxybenzene (4.14 mg/100 g). Both
      conventional and microwave heating caused minor reduction in phenolic compounds.
      The main fatty acids of Brazilian nut oil were linoleic (44.39-48.18%), oleic
      (27.74-31.74%), palmitic (13.09-13.70%) and stearic (8.20-8.91%) acids, while the
      dominant fatty acids of hazelnut (Sivri) oil were oleic acid (80.84%),
      respectively. The heating process caused noticeable change in fatty acid
      compositions of both nut oils.

PMID- 29358829
TI  - The bioaccessibility of iodine in the biofortified vegetables throughout cooking
      and simulated digestion.
AB  - Biofortification of crops with exogenous iodine is a novel strategy to control
      iodine deficiency disorders (IDD). The bioaccessibility of iodine (BI) in the
      biofortified vegetables in the course of soaking, cooking and digestion, were
      examined. Under hydroponics, the concentration of iodine in leafstalks of the
      celery and pakchoi increased with increasing exogenous iodine concentration, 54.8
      63.9% of the iodine absorbed by pakchoi was stored in the soluble cellular
      substance. Being soaked in water within 8 h, the iodine loss rate of the
      biofortified celery was 3.5-10.4% only. More than 80% of the iodine in the
      biofortified celery was retained after cooking under high temperature. The
      highest BI of the biofortified vegetables after digestion in simulated gastric
      and intestinal juice amounted to 74.08 and 68.28%, respectively. Factors
      influencing BI included pH, digestion duration, and liquid-to-solid ratio. The
      high BI of the biofortified vegetables provided a sound reference for the
      promotion of iodine biofortification as a tool to eliminate the IDD.

PMID- 29358831
TI  - Functional properties of Chinese yam (Dioscorea opposita Thunb. cv. Baiyu)
      soluble protein.
AB  - In this study, yam soluble protein (YSP) was extracted from Chinese yam
      (Dioscorea opposita Thunb. cv. Baiyu) and the functional properties were
      investigated under the influence of pH and ionic strength. As results, YSP was
      highly soluble and had better emulsifying activity over a wide range of pH. The
      solubility of YSP decreased in 0.5 and 1.0 M NaCl solution. An increment in NaCl
      concentration reduced the emulsion activity index and emulsion stability index of
      YSP. The oil absorption capacity of YSP was 3.2 ml/g protein. With the increase
      of pH, the foam capacity (FC) and stability (FS) decreased and then increased. FS
      of YSP increased as the salt concentration increased from 0 to 0.5 M, and then
      decreased. The minimal gelation concentration of YSP was 8% (w/v) and 10% YSP gel
      (w/v) had maximum gel strength in 0.1 M NaCl. These results suggested that YSP
      produced by acid precipitation may be used as a protein source with remarkable
      functional properties.

PMID- 29358832
TI  - Effects of enzymes to improve sensory quality of frozen dough bread and analysis
      on its mechanism.
AB  - Baking quality of frozen dough is negatively affected by dough weakening and by a
      reduction in both yeast viability and activity during freezing and frozen
      storage. The objective of this study was to investigate effects of different
      enzymes, such as alpha-amylase, xylanase, celluase, glucose oxidase, and lipase
      on the texture and sensory quality of bread after frozen storage, as well as on
      dough properties, in terms of fermentation characteristics, freezable water
      contents and microstructure. Except for alpha-amylase, other enzymes improved the
      bread sensory quality and got higher overall acceptability, especially xylanase.
      Dough fermentative behavior showed that the maximum heights of frozen dough were
      increased by 33.2, 19.7 and 7.4%, respectively with xylanase, cellulase and
      lipase. Cellulase lowered gas holding ability of dough. Thermodynamic properties
      indicated that addition of enzyme decreased the freezable water contents in
      frozen dough. Scanning electronic microscopy revealed that freezing and frozen
      storage disrupted dough gluten network causing separation of starch granules from
      the gluten matrix. Inclusion of cellulase, xylanase and lipase made the frozen
      dough having a more continuous gluten network and smoother surface, and glucose
      oxidase increased the stability of the gluten work.

PMID- 29358833
TI  - The modulatory effect of polyphenols from green tea, oolong tea and black tea on
      human intestinal microbiota in vitro.
AB  - In the present study, polyphenols from green tea (GTP), oolong tea (OTP) and
      black tea (BTP) were prepared by extraction with hot water and polyamide column
      chromatography. In antioxidant assay in vitro, each tea polyphenols exhibited
      potential activity; the intestinal absorption of GTP, OTP and BTP was
      investigated individually by Caco-2 transwell system, and each sample was poorly
      transported, illustrating a low transport rate for tea polyphenols through cell
      monolayers. The effects of GTP, OTP and BTP on human intestinal microbiota were
      also evaluated, and each sample induced the proliferation of certain beneficial
      bacteria and inhibited Bacteroides-Prevotella and Clostridium histolyticum.
      Moreover, the short-chain fatty acids (SCFA) produced in cultures with tea
      polyphenols were relatively higher. Together, these results suggested GTP, OTP
      and BTP may modulate the intestinal flora and generate SCFA, and contribute to
      the improvements of human health.

PMID- 29358834
TI  - Quality assessment of low-sugar jams enriched with plant raw materials exhibiting
      health-promoting properties.
AB  - Low-sugar gooseberry jams enriched by the addition of black chokeberry,
      elderberry, Japanese quince, flax seeds and wheat germs were examined for the
      content of total polyphenols, total flavonoids, and total anthocyanins as well as
      their antioxidant activity (DPPH, ABTS, and FRAP) and individual phenolic
      compounds. The jams were evaluated immediately after production and after 6 and
      12 months of storage. Samples were stored at chilled temperature (10  degrees C)
      and room temperature (20  degrees C). A significant increase in the level of the
      analyzed components and antioxidant activity were determined in jams with the
      addition of chokeberry, elderberry and Japanese quince, while in the case of
      other plant ingredients the differences were not always significant. Immediately
      after production, the highest levels of total polyphenols (330 mg/100 g), total
      flavonoids (160 mg/100 g) and total anthocyanins (35 mg/100 g) were recorded in
      the gooseberry jam with a 15% addition of chokeberry fruit. In the examined jams,
      p-cumaric acid, ferulic acid, caffeic acid, (+)-catechin and rutin were
      identified and (+)-catechin were determined in the greatest quantities (1.874
      5.660 mg/100 g). The storage conditions of jams determined the level of the
      examined constituents. Storage temperature generally had significant effect on
      the level of compounds with antioxidant properties, lower in the products which
      were chill-stored compared to those stored at room temperature. Anthocyanins were
      found to be the most sensitive components during storage.

PMID- 29358835
TI  - Effect of the essential oils from Melaleuca alternifolia, Melaleuca quinquenervia
      and Backhousia citriodora on the synthesis of ochratoxin A by Aspergillus niger
      and Aspergillus carbonarius isolated from tropical wine grapes.
AB  - The influence of essential oils (EOs) extracted from the leaves of Melaleuca
      alternifolia, Melaleuca quinquenervia and Backhousia citriodora on ochratoxin A
      (OTA) synthesis by fungi was studied. The extraction of EOs was performed by
      hydrodistillation (Clevenger apparatus) over a 2-h period and subsequently
      analyzed by GC-MS and GC-FID. The toxigenic activity of the essential oils
      (31.25; 15.62 and 7.81 ug mL-1) was evaluated by inhibiting the production of OTA
      by Aspergillus niger and Aspergillus carbonarius in Czapek agar medium culture.
      The quantification of the toxin was performed by HPLC. The production of OTA was
      dependent on the fungal species, incubation temperature (15 and 25  degrees C)
      and the presence of the essential oils. In tests carried out at 15  degrees C,
      the oils caused a reduction in OTA synthesis that ranged from 57.60 to 76.93% and
      from 54.78 to 98.68% for the fungal species A. carbonarius and A. niger,
      respectively. At 25  degrees C, reductions ranged from the 38.66 to 75.93% and
      from 17.94 to 71.79% for the respective fungi. The study concluded that natural
      products could be potential biocontrol agents against OTA contamination in food.

PMID- 29358836
TI  - Sensory attributes and volatile composition of a dry white wine under different
      packing configurations.
AB  - The aim of this work was to study the effect of different configurations of
      packaging on the volatile composition and sensory properties of a white wine.
      Certain oenological parameters were also evaluated. Bag-in-box (BIB) and glass
      bottles sealed with two different cork stoppers, natural and Neutrocork
      (technical), were used in the experiments. Analysis were carried out before
      packaging and after 3, 6 and 12 months of storage. Results showed that wines
      packaged in BIB presented higher levels of brown color than wines in bottles
      sealed with corks. In all packaging configurations, the content of free SO2
      decreased with storage time; however, BIB wines showed a lower content of free
      SO2 than bottle wines during 12 months. Moreover, wines under BIB presented a
      significant lower amount of 2-phenylethanol, 2-phenylethyl acetate, isoamyl
      acetate, ethyl butanoate, ethyl hexanoate, ethyl octanoate, linalool and beta
      damascenone than bottled wines.

PMID- 29358837
TI  - Incorporation of Lactobacillus plantarum and zeolites in poultry feed can reduce
      aflatoxin B1 levels.
AB  - The aim of this work was to evaluate the incorporation of a freeze-dried
      probiotic strain (Lactobacillus plantarum CIDCA 83114) into zeolites. The
      bacteria-zeolite mixture was added to poultry feed together with thyme, and the
      obtained product was stored for 60 days at 25  degrees C and 60-70% relative
      humidity. The ability of the obtained product to remove aflatoxin B1 (AFB1) was
      studied. The highest bacterial viability was observed when 50% w/w bacteria were
      added to zeolites. The bacterial:zeolite mixtures were then incorporated into
      poultry feed containing or not thyme. Initial counts of L. plantarum were in the
      range of 1-2 * 108 CFU/g for all samples. In all cases, bacterial viability
      decreased one logarithmic order after 20 days of storage, and three logarithmic
      orders after 60 days. No significant viability loss was observed after exposure
      of the poultry feed to gastro-intestinal conditions. Freeze-dried L. plantarum
      and zeolite were able to remove AFB1, with an average reduction of 20 and 80%,
      respectively. Moreover, the freeze-dried bacteria-zeolite mixture was capable to
      remove up to 90% AFB1. This work contributes to enhance the nutritional quality
      of poultry feed, with a strong impact in production.

PMID- 29358838
TI  - Identification of volatile compound markers during the ripening and senescence of
      lulo (Solanum quitoense Lam.).
AB  - Lulo (Solanum quitoense Lam.) is an exotic fruit cultivated in Colombia. During
      ripening and senescence, this climactic fruit undergoes biochemical processes
      that produce the volatiles responsible for its aroma. This study aimed to
      evaluate the changes in the volatile content during the ripening and senescence
      of lulo. Analysis of the volatile composition of lulo harvested in each of its
      five ripening stages and during its senescence time when stored at 18 +/- 2 
      degrees C was performed using HS-SPME with GC-MS. Throughout ripening, the most
      notable change was the transformation of alcohols such as (Z)-3-hexen-1-ol and 1
      penten-3-ol to afford esters such as (Z)-3-hexenyl acetate and ketones such as 1
      penten-3-one. Some acids reacted with alcohols to produce acetate and hexanoate
      esters, concentrations which increased more than sixfold between stage one and
      five. Moreover, all the major compounds were C6 straight chain compounds related
      to the lipoxygenase pathway. During senescence, majority of compounds were methyl
      esters, which increased in concentration consistently until day eight.
      Remarkably, the content of methyl butanoate increased from 0.9% of the total
      amount of volatiles on day two up to 76.4% on day eight. Some of these volatiles
      are probably contributors to the "off flavor" during senescence.

PMID- 29358839
TI  - Capillary electrophoresis to approach sorbate usage in processed meat products in
      Brazil.
AB  - Sorbate is a highly used preservative in a wide range of processed foods,
      including meat products. In this work sorbate usage in commercial processed meat
      products from the Brazilian market was evaluated. A capillary electrophoresis
      method for sorbate analysis using ethanol:water extraction solution (1:2, v/v)
      and sodium tetraborate (20 mmol L-1) electrolyte solution was validated. Low
      limits of detection (0.4 mg L-1) and quantification (1.0 mg L-1), good precision
      (RSD = 3.6%) and suitable accuracy (70.2%, RSD = 1.8%) were attained. Linearity
      was observed from 1.0 to 15.8 mg L-1, with r >= 0.999. The proposed method was
      applied to Brazilian pork and hot dog sausages, salami, ham and mortadella. A
      peak of sorbate between 4 and 6 min was found in pork and hot dog sausages,
      poultry and pork mortadella, but not in ham and salami. The sorbate levels ranged
      from 54.0 to 976.4 mg kg-1. Sorbate concentration exceeded the 200 mg kg-1 limit
      of the Brazilian legislation in all sorts of products in the majority of the
      brands despite there being no information regarding sorbate on the label. These
      results indicated the widespread use of sorbate, turning this into food for
      thought.

PMID- 29358840
TI  - Using a patterned microtexture to reduce polyethylene wear in metal-on
      polyethylene prosthetic bearing couples.
AB  - The longevity of metal-on-polyethylene prosthetic hip joint bearings, in which a
      CoCrMo femoral head articulates with a polyethylene liner, is often limited by
      polyethylene wear and osteolysis caused by polyethylene wear particles. Current
      approaches to reduce polyethylene wear include improving the mechanical
      properties of the polyethylene liner, and/or manufacturing ultra-smooth
      articulating surfaces. In contrast, this experimental work shows that adding a
      patterned microtexture of concave "dimples" to a polished CoCrMo surface
      significantly reduces polyethylene wear by promoting the formation of an
      elastohydrodynamic lubricant film, which reduces contact between the CoCrMo and
      polyethylene bearing surfaces. Using a gravimetric method to measure polyethylene
      pin wear during pin-on-disc experiments, it was demonstrated that microtextured
      CoCrMo caused reduced polyethylene wear compared to polished CoCrMo surfaces.
      Wear was quantified for different polyethylene materials currently used in
      commercial prosthetic hip joint bearings, and for several microtexture
      geometries. It was also documented by correlating polyethylene wear with surface
      topography measurements that the patterned microtexture reduced contact between
      the articulating bearing surfaces.

PMID- 29358842
TI  - Elevated Level of Troponin but Not N-Terminal Probrain Natriuretic Peptide Is
      Associated with Increased Risk of Sudden Cardiac Death in Hypertrophic
      Cardiomyopathy Calculated According to the ESC Guidelines 2014.
AB  - The aim of this study was to assess the relationship between biomarkers (high
      sensitive troponin I [hs-TnI], N-Terminal probrain natriuretic peptide [NT
      proBNP]) and calculated 5-year percentage risk score of sudden cardiac death
      (SCD) in hypertrophic cardiomyopathy (HCM). Methods. In 46 HCM patients (mean age
      39 +/- 7 years, 24 males and 22 females), echocardiographic examination,
      including the stimulating maneuvers to provoke maximized LVOT gradient, had been
      performed and next ECG Holter was immediately started. After 24 hours, the ECG
      Holter was finished and the hs-TnI and NT-proBNP have been measured. Patients
      were divided according to 1/value of both biomarkers (hs-TnI-positive and hs-TnI
      negative subgroups) and 2/(NT-proBNP lower and higher subgroup divided by
      median). Results. In comparison between 19 patients (hs-TnI positive) versus 27
      patients (hs-TnI negative), the calculated 5-year percentage risk of SCD in HCM
      was significantly greater (6.38 +/- 4.17% versus 3.81 +/- 3.23%, P < 0.05). In
      comparison between higher NT-proBNP versus lower NT-proBNP subgroups, the
      calculated 5-year percentage risk of SCD in HCM was not significantly greater
      (5.18 +/- 3.63% versus 4.14 +/- 4.18%, P > 0.05). Conclusions. Patients with HCM
      and positive hs-TnI test have a higher risk of SCD estimated according to SCD
      calculator recommended by the ESC Guidelines 2014 than patients with negative hs
      TnI test.

PMID- 29358841
TI  - Usefulness of Age-Stratified N-Terminal Prohormone of Brain Natriuretic Peptide
      for Diagnosing Kawasaki Disease.
AB  - N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was recently
      reported as a biomarker for diagnosing Kawasaki disease (KD). The basal NT-proBNP
      level, however, gradually decreases with age. We investigated the usefulness of
      an age-stratified cutoff value of NT-proBNP for diagnosing KD. All the patients
      enrolled in this study visited Chonnam National University Hospital between
      December 2007 and March 2016. The KD groups consisted of 214 patients with
      complete KD and 129 patients with incomplete KD. The control group included 62
      children with simple febrile illness but without heart disease. Laboratory data
      including NT-proBNP level were evaluated. Each group was divided into subgroups
      according to patient age (<6 months, 6-12 months, 12-24 months, and >24 months),
      and different cutoff values of NT-proBNP were calculated. The cutoff values of NT
      proBNP used to diagnose total KD and incomplete KD were 762 and 762 pg/mL (<6
      months), 310 and 310 pg/mL (6-12 months), 326 and 326 pg/mL (12-24 months), and
      208 and 137 pg/mL (>24 months), respectively. In conclusion, age-stratified NT
      proBNP is a useful biomarker for the differential diagnosis of KD in patients
      with a simple febrile illness.

PMID- 29358843
TI  - Statistical Power in Two-Level Hierarchical Linear Models with Arbitrary Number
      of Factor Levels.
AB  - As the US health care system undergoes unprecedented changes, the need for
      adequately powered studies to understand the multiple levels of main and
      interaction factors that influence patient and other care outcomes in
      hierarchical settings has taken center stage. We consider two-level models where
      n lower-level units are nested within each of J higher-level clusters (e.g.
      patients within practices and practices within networks) and where two factors
      may have arbitrary a and b factor levels, respectively. Both factors may
      represent a * b treatment combinations, or one of them may be a pretreatment
      covariate. Consideration of both factors at the same higher or lower hierarchical
      level, or one factor per hierarchical level yields a cluster (C), multisite (M)
      or split-plot randomized design (S). We express statistical power to detect main,
      interaction, or any treatment effects as a function of sample sizes (n, J), a and
      b factor levels, intraclass correlation rho and effect sizes delta given each
      design d ? {C, M, S}. The power function given a, b, rho, delta and d determines
      adequate sample sizes to achieve a minimum power requirement. Next, we compare
      the impact of the designs on power to facilitate selection of optimal design and
      sample sizes in a way that minimizes the total cost given budget and logistic
      constraints. Our approach enables accurate and conservative power computation
      with a priori knowledge of only three effect size differences regardless of how
      large a * b is, simplifying previously available computation methods for health
      services and other researches.

PMID- 29358844
TI  - Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection.
AB  - Herpes simplex virus 1 (HSV) encephalitis (HSE) has serious neurological
      complications, involving behavioral and cognitive impairments that cause
      significant morbidity and a reduced quality of life. We showed that HSE results
      from dysregulated central nervous system (CNS) inflammatory responses. We
      hypothesized that CNS inflammation is casually involved in behavioral
      abnormalities after HSE and that treatment with ACV and pooled human
      immunoglobulin (IVIG), an immunomodulatory drug, would improve outcomes compared
      to mice treated with phosphate buffered saline (PBS) or ACV alone. Anxiety levels
      were high in HSV-infected PBS and ACV-treated mice compared to mice treated with
      ACV + IVIG, consistent with reports implicating inflammation in anxiety induced
      by lipopolysaccharide (LPS) or stress. Female, but not male, PBS-treated mice
      were cognitively impaired, and unexpectedly, ACV was protective, while the
      inclusion of IVIG surprisingly antagonized ACV's beneficial effects. Distinct
      serum proteomic profiles were observed for male and female mice, and the
      antagonistic effects of ACV and IVIG on behavior were paralleled by similar
      changes in the serum proteome of ACV- and ACV + IVIG-treated mice. We conclude
      that inflammation and other factors mediate HSV-induced behavioral impairments
      and that the effects of ACV and IVIG on behavior involve novel mechanisms.

PMID- 29358845
TI  - Effect of Voluntary Wheel Running on Striatal Dopamine Level and Neurocognitive
      Behaviors after Molar Loss in Rats.
AB  - The aim of the present study is to evaluate the effect of voluntary wheel running
      on striatal dopamine level and behavior of cognition and emotion in molar loss
      rats. Twenty-four Sprague-Dawley rats were enrolled in this study and randomly
      divided into following 4 groups: control group (C group), molar loss group (ML
      group), 1-week physical exercise before molar loss group (1W-ML group), and 4
      week physical exercise before molar loss group (4W-ML group). The rats both in 4W
      ML and 1W-ML groups were placed in the voluntary running wheel in order to
      exercise for 4 weeks and 1 week, respectively. Then, the rats in 4W-ML, 1W-M, and
      ML groups received bilateral molar loss operation. After 10 days, striatal
      dopamine level was detected by in vivo microdialysis coupled with high
      performance liquid chromatography (HPLC) and electrochemical detection. All the
      rats received behavior test after microdialysis detection. The behavior tests
      including passive avoidance test were used to assess cognition and elevated plus
      maze test for emotion. The results indicated that voluntary wheel running
      promoted striatal dopamine level in rats of molar loss. Behavioral data indicated
      that voluntary wheel running promoted cognition and emotion recovery after molar
      loss. Therefore, we concluded physical exercise significantly improved the
      neurocognitive behaviors and increased the striatal dopamine level after molar
      loss in rats.

PMID- 29358846
TI  - Natural biotic resources in LCA: Towards an impact assessment model for
      sustainable supply chain management.
AB  - Natural resources, biotic and abiotic, are fundamental from both the ecological
      and socio-economic point of view, being at the basis of life-support. However,
      since the demand for finite resources continues to increase, the sustainability
      of current production and consumption patterns is questioned both in developed
      and developing countries. A transition towards an economy based on biotic
      renewable resources (bio-economy) is considered necessary in order to support a
      steady provision of resources, representing an alternative to an economy based on
      fossil and abiotic resources. However, to ensure a sustainable use of biotic
      resources, there is the need of properly accounting for their use along supply
      chains as well as defining a robust and comprehensive impact assessment model.
      Since so far naturally occurring biotic resources have gained little attention in
      impact assessment methods, such as life cycle assessment, the aim of this study
      is to enable the inclusion of biotic resources in the assessment of products and
      supply chains. This paper puts forward a framework for biotic resources
      assessment, including: i) the definition of system boundaries between ecosphere
      and technosphere, namely between naturally occurring and man-made biotic
      resources; ii) a list of naturally occurring biotic resources which have a
      commercial value, as basis for building life cycle inventories (NOBR, e.g. wild
      animals, plants etc); iii) an impact pathway to identify potential impacts on
      both resource provision and ecosystem quality; iv) a renewability-based indicator
      (NOBRri) for the impact assessment of naturally occurring biotic resources,
      including a list of associated characterization factors. The study, building on a
      solid review of literature and of available statistical data, highlights and
      discusses the critical aspects and paradoxes related to biotic resource inclusion
      in LCA: from the system boundaries definition up to the resource
      characterization.

PMID- 29358847
TI  - Systematic analysis of secondary life cycle inventories when modelling
      agricultural production: A case study for arable crops.
AB  - Analysis of agricultural production with life cycle based methodologies is data
      demanding. To build comprehensive life cycle inventories, secondary datasets are
      commonly used when primary data are not available. However, different inventory
      data and modelling approaches are used to populate secondary datasets, leading to
      different results. The present study analyses the features of twelve secondary
      datasets to support datasets selection and proper interpretation of results. We
      assess twelve datasets for arable crop production in France, as modelled in three
      databases often used in the LCA field (Agri-footprint, ecoinvent and AGRIBALYSE).
      First, we compared system boundaries and general assumptions. Second, we focused
      on foreground systems comparing, inventory data, data sources and modelling
      approaches. Third, we performed a contribution analysis of impact assessment
      results to identify modelling choices that contribute most to differences in the
      results. Nine relevant elements were identified and assessed: definition of
      system boundaries and modelling of agricultural practices, characteristics of
      inventory data, agricultural operations, fertiliser application and fate, plant
      protection products application and fate, heavy metals inputs to the agricultural
      system and fate, irrigation assumptions, land use and transformation. The
      datasets differ greatly with respect to these elements. Hence, recommendations
      are drawn from the datasets comparison, supporting the selection of the datasets
      coherently with the goal and scope of a study and interpretation of results.

PMID- 29358848
TI  - Antilipotoxicity Activity of Osmanthus fragrans and Chrysanthemum morifolium
      Flower Extracts in Hepatocytes and Renal Glomerular Mesangial Cells.
AB  - The excess influx of free fatty acids (FFAs) into nonadipose tissues, such as
      those of liver and kidney, induces lipotoxicity leading to hepatic steatosis and
      renal dysfunction. The aim of this study was to investigate the protective
      effects of methanolic flower extracts of Osmanthus fragrans (OF) and
      Chrysanthemum morifolium (CM) against FFA-induced lipotoxicity in hepatocytes
      (human HepG2 cells) and renal glomerular mesangial cells (mouse SV40-Mes13
      cells). The results showed that OF and CM significantly suppressed FFA-induced
      intracellular triacylglycerol accumulation via partially inhibiting the gene
      expression of sterol regulatory element-binding protein-1c (SREBP-1c) and
      glycerol-3-phosphate acyltransferase (GPAT) in HepG2 cells. Both extracts
      inhibited reactive oxygen species (ROS) generation by FFA-stimulated HepG2 cells.
      OF and CM also suppressed the mRNA expression of interleukin- (IL-) 1beta, IL-6,
      IL-8, tumor necrosis factor- (TNF-) alpha, and transforming growth factor- (TGF-)
      beta by HepG2 cells treated with conditioned medium derived from
      lipopolysaccharide-treated THP-1 monocytes. Furthermore, OF and CM effectively
      inhibited oleate-induced cellular lipid accumulation, TGF-beta secretion, and
      overexpression of fibronectin in mesangial cells. In conclusion, OF and CM
      possess hepatoprotective activity by inhibiting hepatic fat load and inflammation
      and renal protection by preventing FFA-induced mesangial extracellular matrix
      formation.

PMID- 29358849
TI  - Mitofusin 2 Promotes Apoptosis of CD4+ T Cells by Inhibiting Autophagy in Sepsis.
AB  - Apoptosis of CD4+ T cells is a primary pathophysiological mechanism of immune
      dysfunction in the pathogenesis of sepsis. Mitofusin 2 (Mfn2), an integral
      mitochondrial outer membrane protein, has been confirmed to be associated with
      cellular metabolism, proliferation, and apoptosis. The function of Mfn2 in CD4+ T
      cell apoptosis in sepsis is poorly understood. Here, we discovered increased in
      vivo Mfn2 expression, autophagy deficiency, and elevated cell apoptosis in murine
      splenic CD4+ T cells after cecal ligation and puncture (CLP). We also observed
      almost identical results in splenic CD4+ T cells upon lipopolysaccharide (LPS)
      stimulation in vitro. Furthermore, overexpression of Mfn2 resulted in impaired
      autophagy and increased apoptosis in Jurkat cells. Pharmacological inhibition of
      autophagy with 3-methyladenine enhanced Mfn2 overexpression-induced cell
      apoptosis. In addition, overexpression of Mfn2 downregulated phorbol myristate
      acetate (PMA)/ionomycin-, rapamycin- and starvation-induced autophagy in Jurkat T
      cells. Taken together, these data indicate a critical role of Mfn2 in CD4+ T cell
      apoptosis in sepsis and the underlying mechanism of autophagy deficiency.

PMID- 29358850
TI  - Changes in Etiologies of Hospitalized Patients with Liver Cirrhosis in Beijing
      302 Hospital from 2002 to 2013.
AB  - Background: Over the last 20 years, the prevalence of hepatitis B virus (HBV)
      infection in China has decreased gradually due to the application of a national
      HBV vaccination program. In contrast, the prevalence of alcoholic liver disease
      (ALD), nonalcoholic fatty liver disease, autoimmune liver disease, and drug
      induced liver injury has markedly increased. Methods: We conducted a
      retrospective review of 82,562 hospitalized patients diagnosed with liver
      cirrhosis in Beijing 302 Hospital from 2002 to 2013. Results: The top four
      etiologies of cirrhosis were HBV, HCV, ALD, and autoimmune liver disease. The
      percentage of HBV cirrhosis decreased from 81.53% in 2002 to 66.0% in 2013,
      whereas the frequency of alcoholic cirrhosis increased from 3.34% in 2002 to
      8.40% in 2013. Females (84.34%) accounted for the majority of cirrhotic patients
      with autoimmune liver diseases. Males accounted for 80.16% of HBV cirrhosis
      patients and 98.02% of alcoholic cirrhosis patients. Conclusion: In Beijing 302
      Hospital, the top four etiologies of cirrhosis were HBV, HCV, ALD, and autoimmune
      liver disease. Over the last 12 years, the prevalence of HBV cirrhosis has
      decreased gradually, whereas that of alcoholic cirrhosis has increased
      significantly.

PMID- 29358851
TI  - Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced
      Cardiac Hypertrophy in Mice.
AB  - Background: Interleukin- (IL-) 22 is considered a proinflammatory cytokine.
      Recent evidence has demonstrated that it plays a role in cardiovascular diseases.
      In the recent study, we investigate whether IL-22 is involved in cardiac
      hypertrophy. Methods: Angiotensin II was used to build hypertrophy model and the
      IL-22 and IL-22 receptor 1 (IL-22R1) levels in heart tissue were measured. In
      addition, angiotensin II-treated mice received an injection of anti-IL-22
      neutralizing antibody (nAb) to investigate the effects of IL-22 nAb on myocardial
      hypertrophy, cardiac function, and cardiac fibrosis; the activation of the
      signaling pathway and the prohypertrophic inflammatory cytokine mRNA levels was
      detected. Furthermore, the effect of IL-22 nAb on angiotensin II-induced
      hypertrophy in vitro was also determined. Results: IL-22 and IL-22R1 levels were
      significantly increased after angiotensin II infusion. Anti-IL-22 nAb
      significantly alleviated the severity of hypertrophy, prevented systolic and
      diastolic abnormalities, reduced cardiac fibrosis, STAT3 and ERK phosphorylation,
      and downregulated the mRNA expression of IL-17, IL-6, IL-1beta, IFN-gamma, and
      TNF-alpha. In addition, IL-22 nAb attenuated angiotensin II-induced hypertrophy
      in H9C2 cells. Conclusion: Our data demonstrated that neutralization of IL-22
      alleviated angiotensin II-induced cardiac hypertrophy. The downregulation of IL
      22 may be a novel therapeutic strategy to prevent cardiac hypertrophy.

PMID- 29358852
TI  - Luteolin Treatment Protects against Renal Ischemia-Reperfusion Injury in Rats.
AB  - Renal ischemia-reperfusion (I/R) injury is a common but severe scientific
      problem. Luteolin has great anti-inflammatory and antioxidant effects. In this
      study, we studied the effect of luteolin on renal I/R injury in rats.
      Intragastric administration of luteolin or saline was performed in Sprague-Dawley
      rats before (40 mg/kg for three days) and after (one day) renal I/R modeling.
      Kidney and blood samples were harvested to detect the severity of renal injury 24
      hours after operation. The results showed that luteolin-treated rats exhibited
      milder histomorphological changes with lower scores of renal histological
      lesions; lower blood urea nitrogen and creatinine levels; lower renal
      malondialdehyde (MDA), 8-oxo-deoxyguanosine (8-OHdG), and myeloperoxidase (MPO)
      levels; and higher superoxide dismutase (SOD) and catalase (CAT) activities in
      the kidney. Luteolin attenuated the increased levels of serum and renal tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6, renal high
      mobility group box-1 (HMGB1), and nuclear factor kappa beta (NF-kappaB)
      expression levels in I/R rats. Furthermore, luteolin treatment significantly
      reduced renal cell apoptosis and endoplasmic reticulum (ER) stress caused by
      renal I/R injury. In conclusion, luteolin improved renal function in I/R rats by
      reducing oxidative stress, neutrophil infiltration, inflammation, renal cell
      apoptosis, and expression of HMGB1 and NF-kappaB, and ER stress.

PMID- 29358853
TI  - Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis.
AB  - The renin angiotensin system (RAS) is classically conceived as a circulating
      hormonal system involved in blood pressure control and hydroelectrolyte balance.
      The discovery that RAS components are locally expressed in a wide range of organs
      and tissues, including the liver, pointed to a role for this system in the
      pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It
      has been widely reported that the classical RAS axis composed by the angiotensin
      converting enzyme (ACE)-angiotensin (Ang) II-Ang type 1 (AT1) receptor mediates
      pro-inflammatory, pro-thrombotic, and pro-fibrotic processes. On the other hand,
      the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a
      protective role by frequently opposing Ang II action. Chronic hepatitis B (CHB)
      is one of the leading causes of liver fibrosis, accounting for the death of
      nearly one million people worldwide. Liver fibrosis is a key factor to determine
      therapeutic interventions for patients with CHB. However, the establishment of
      non-invasive and accurate methods to detect reversible stages of liver fibrosis
      is still a challenge. In an elegant study published in the 36th issue of the
      World Journal of Gastroenterology, Noguchi et al showed the predictive value of
      serum ACE levels in detecting not only advanced stages of liver fibrosis but also
      initial and intermediate fibrotic stages. The serum levels of ACE might represent
      an accurate, non-invasive, widely available, and easy method to evaluate fibrosis
      related to CHB. Moreover, therapies involving the inhibition of the classical RAS
      axis components might be promising in the control of CHB-related liver fibrosis.

PMID- 29358854
TI  - Mechanisms of autophagy activation in endothelial cell and their targeting during
      normothermic machine liver perfusion.
AB  - Ischaemia-reperfusion injury (IRI) is the leading cause of injury seen in the
      liver following transplantation. IRI also causes injury following liver surgery
      and haemodynamic shock. The first cells within the liver to be injured by IRI are
      the liver sinusoidal endothelial cells (LSEC). Recent evidence suggests that LSEC
      co-ordinate and regulates the livers response to a variety of injuries. It is
      becoming increasingly apparent that the cyto-protective cellular process of
      autophagy is a key regulator of IRI. In particular LSEC autophagy may be an
      essential gatekeeper to the development of IRI. The recent availability of liver
      perfusion devices has allowed for the therapeutic targeting of autophagy to
      reduce IRI. In particular normothermic machine liver perfusion (NMP-L) allow the
      delivery of pharmacological agents to donor livers whilst maintaining
      physiological temperature and hepatic flow rates. In this review we summarise the
      current understanding of endothelial autophagy and how this may be manipulated
      during NMP-L to reduce liver IRI.

PMID- 29358855
TI  - Human small intestine is capable of restoring barrier function after short
      ischemic periods.
AB  - AIM: To assess intestinal barrier function during human intestinal ischemia and
      reperfusion (IR). METHODS: In a human experimental model, 6 cm of jejunum was
      selectively exposed to 30 min of ischemia (I) followed by 30 and 120 min of
      reperfusion (R). A sham procedure was also performed. Blood and tissue was
      sampled at all-time points. Functional barrier function was assessed using dual
      sugar absorption tests with lactulose (L) and rhamnose (R). Plasma concentrations
      of citrulline, an amino acid described as marker for enterocyte function were
      measured as marker of metabolic enterocytes restoration. Damage to the epithelial
      lining was assessed by immunohistochemistry for tight junctions (TJs), by plasma
      marker for enterocytes damage (I-FABP) and analyzed by electron microscopy (EM)
      using lanthanum nitrate as an electrondense marker. RESULTS: Plasma L/R ratio's
      were significantly increased after 30 min of ischemia (30I) followed by 30 min of
      reperfusion (30R) compared to control (0.75 +/- 0.10 vs 0.20 +/- 0.09, P < 0.05).
      At 120 min of reperfusion (120R), ratio's normalized (0.17 +/- 0.06) and were not
      significantly different from control. Plasma levels of I-FABP correlated with
      plasma L/R ratios measured at the same time points (correlation: 0.467, P <
      0.01). TJs staining shows distortion of staining at 30I. An intact lining of TJs
      was again observed at 30I120R. Electron microscopy analysis revealed disrupted
      TJs after 30I with paracellular leakage of lanthanum nitrate, which restored
      after 30I120R. Furthermore, citrulline concentrations closely paralleled the
      histological perturbations during intestinal IR. CONCLUSION: This study directly
      correlates histological data with intestinal permeability tests, revealing that
      the human gut has the ability of to withstand short episodes of ischemia, with
      morphological and functional recovery of the intestinal barrier within 120 min of
      reperfusion.

PMID- 29358857
TI  - Exploring pathogenesis of primary biliary cholangitis by proteomics: A pilot
      study.
AB  - AIM: To explore the pathogenesis of primary biliary cholangitis (PBC) by
      identifying candidate autoantibodies in serum samples by proteomics and
      bioinformatics. METHODS: Nine antimitochondrial antibody (AMA)-positive PBC
      patients and nine age- and sex-matched AMA-negative PBC patients were recruited.
      Antigen enrichment technology was applied to capture autoantigens of human
      intrahepatic biliary epithelial cells (HiBECs) that are recognized by
      autoantibodies from the sera of PBC patients. Candidate autoantigens were
      identified by label-free mass spectrometry. Bioinformatics analysis with MaxQuant
      software (version 1.5.2.8), DAVID platform, and Cytoscape v.3.0 allowed
      illustration of pathways potentially involved in the pathogenesis of PBC.
      RESULTS: In total, 1081 candidate autoantigen proteins were identified from the
      PBC patient pool. Among them, 371 were determined to be significantly
      differentially expressed between AMA-positive and -negative PBC patients (P <
      0.05). Fisher's exact test was performed for enrichment analysis of Gene Ontology
      protein annotations (biological processes, cellular components, and molecular
      functions) and the Kyoto Encyclopedia of Genes and Genomes pathways.
      Significantly different protein categories were revealed between AMA-positive and
      -negative PBC patients. As expected, autoantigens related to mitochondria were
      highly enriched in AMA-positive PBC patients. However, lower levels of AMA were
      also detected in AMA-negative PBC patients. In addition, autoantigens of AMA
      negative PBC patients were mainly involved in B-cell activation, recognition of
      phagocytosis, and complement activation. CONCLUSION: AMA-negative PBC individuals
      may not exist, but rather, those patients exhibit pathogenesis pathways different
      from those of AMA-positive PBC. Comprehensive research is needed to confirm these
      observations.

PMID- 29358858
TI  - Influence of TBX21 T-1993C variant on autoimmune hepatitis development by Yin
      Yang 1 binding.
AB  - AIM: To investigated the mechanism of the association between the TBX21 T-1993C
      promoter polymorphism and autoimmune hepatitis type 1 (AIH-1) development.
      METHODS: In vivo, In vivo, and reporter analyses were performed to determine the
      function of transcription factors binding to the T-1993C element of the TBX21
      promoter in human CD4+ T and B cell lines. Flow cytometry and quantitative real
      time PCR were used to analyze T-box transcription factor (T-bet) and interferon
      gamma (IFN-gamma) expressions in CD4+ T cells, B cells and monocytes from the
      peripheral blood of AIH-1 patients including 5-1993TC and 15-1993TT genotype
      carriers, and healthy controls including 10-1993TC and 25-1993TT genotype
      carriers. Furthermore, a range of biochemical indices was measured simultaneously
      in the blood of AIH-1 patients. RESULTS: TBX21-1993C allele created a strong Yin
      Yang 1 (YY1)-binding site and decreased transcriptional activity of TBX21
      promoter in human CD4+ T and B cells. Higher levels of T-bet and IFN-gamma were
      detected in the circulating CD4+ T cells and B cells of AIH-1 patients carrying
      the TBX21-1993 TT genotype compared with the patients carrying the -1993 TC
      genotype and controls with the -1993 TC genotype. T-bet expression levels of
      circulating T cells and B cells were positively correlated with AIH-1 disease
      activity. Knockdown of YY1 with siRNA caused increased expression of T-bet and
      IFN-gamma in peripheral blood mononuclear cells in AIH-1 patients. CONCLUSION:
      The repression of TBX21 expression by high-affinity binding of YY1 to the -1993C
      allele may contribute to a decreased development of AIH-1 via suppression of type
      1 immunity.

PMID- 29358856
TI  - Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia
      and reperfusion in rats: New insights.
AB  - AIM: To provide new insights in treatment of colitis and ischemia and reperfusion
      in rats using stable gastric pentadecapeptide BPC 157. METHODS: Medication [BPC
      157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived
      colon segment. During reperfusion, medication was BPC 157 or saline. We recorded
      (USB microscope camera) vessel presentation through next 15 min of ischemic
      colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative
      stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC
      rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had
      additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157
      bath. RESULTS: Commonly, in colon segment (25 mm, 2 ligations on left colic
      artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC +
      OB-rats, BPC 157 (10 MUg/kg) bath (1 mL/rat) increased vessel presentation,
      inside/outside arcade interconnections quickly reappeared, mucosal folds were
      preserved and the pale areas were small and markedly reduced. BPC 157
      counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg).
      MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In
      addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely
      spared mucosa with very small pale areas and no gross mucosal defects; the
      treated colon segment was of normal diameter, and only small adhesions were
      present. CONCLUSION: BPC 157 is a fundamental treatment that quickly restores
      blood supply to the ischemically injured area and rapidly activates collaterals.
      This effect involves the NO system.

PMID- 29358859
TI  - Astragaloside IV inhibits pathological functions of gastric cancer-associated
      fibroblasts.
AB  - AIM: To investigate the inhibitory effect of astragaloside IV on the pathological
      functions of cancer-associated fibroblasts, and to explore the underlying
      mechanism. METHODS: Paired gastric normal fibroblast (GNF) and gastric cancer
      associated fibroblast (GCAF) cultures were established from resected tissues.
      GCAFs were treated with vehicle control or different concentrations of
      astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control
      treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823
      human gastric cancer cells. Proliferation, migration and invasion capacities of
      BGC-823 cells were determined by MTT, wound healing, and Transwell invasion
      assays, respectively. The action mechanism of astragaloside IV was investigated
      by detecting the expression of microRNAs and the expression and secretion of the
      oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor
      suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different
      groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and
      NANOG in BGC-823 cells cultured with different conditioned media was also
      examined. RESULTS: GCAFs displayed higher capacities to induce BGC-823 cell
      proliferation, migration, and invasion than GNFs (P < 0.01). Astragaloside IV
      treatment strongly inhibited the proliferation-, migration- and invasion
      promoting capacities of GCAFs (P < 0.05 for 10 MUmol/L, P < 0.01 for 20 MUmol/L
      and 40 MUmol/L). Compared with GNFs, GCAFs expressed a lower level of microRNA
      214 (P < 0.01) and a higher level of microRNA-301a (P < 0.01). Astragaloside IV
      treatment significantly up-regulated microRNA-214 expression (P < 0.01) and down
      regulated microRNA-301a expression (P < 0.01) in GCAFs. Reestablishing the
      microRNA expression balance subsequently suppressed M-CSF production (P < 0.01)
      and secretion (P < 0.05), and elevated TIMP2 production (P < 0.01) and secretion
      (P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG
      expression in BGC-823 cells was abolished by astragaloside IV. CONCLUSION:
      Astragaloside IV can inhibit the pathological functions of GCAFs by correcting
      their dysregulation of microRNA expression, and it is promisingly a potent
      therapeutic agent regulating tumor microenvironment.

PMID- 29358860
TI  - Prevalence and outcomes of pancreatic cystic neoplasms in liver transplant
      recipients.
AB  - AIM: To determine the prevalence, characteristics and clinical course of
      pancreatic cystic neoplasms (PCNs) in liver transplantation (LT) recipients.
      METHODS: We retrospectively studied consecutive patients who underwent LT between
      January 1998 to April 2016. Clinical and laboratory data were obtained from
      patient medical records. Imaging findings on computed tomography and magnetic
      resonance cholangiopancreatography were reviewed by two radiologists. RESULTS:
      During the study period, 872 patients underwent cadaveric LT. Pancreatic cysts
      were identified in 53/872 (6.1%) and 31/53 (58.5%) were PCNs [28 intraductal
      papillary mucinous neoplasm (IPMN), 2 mucinous cystic neoplasm (MCN), 1 serous
      cystadenoma]. Patients with PCNs exhibited less male predominance (55% vs 73%, P
      = 0.03) compared to patients without pancreatic cysts. Thirteen patients (42%)
      were diagnosed with PCN pre-LT while 18 patients (58%) developed PCN post-LT. The
      median size of PCNs was 13mm [interquartile range (IQR) 10-20 mm]. All IPMNs were
      side-branch type. Most PCNs were found in the head and body of pancreas (37%
      each), followed by the tail (25%). Five patients underwent further evaluation
      with endoscopic ultrasound. Progress imaging was performed on 81% of patients.
      PCNs remained stable in size and number in all but 2 patients. During a median
      follow up of 39 mo (IQR 26-58 mo), the 2 (6%) patients with MCN underwent
      pancreatectomy. No PCN patient developed pancreatic adenocarcinoma, while 5 died
      from illnesses unrelated to the PCN. Among patients without PCN, 1/841 (0.1%)
      developed pancreatic adenocarcinoma. CONCLUSION: The prevalence of PCNs in LT
      recipients was similar to the general population (3.6%, 31/872). Side-branch
      IPMNs do not appear to have accelerated malignant potential in post-LT patients,
      indicating the current surveillance guidelines are applicable to this group.

PMID- 29358861
TI  - Analysis of 12 variants in the development of gastric and colorectal cancers.
AB  - AIM: To evaluate the relation between 12 polymorphisms and the development of
      gastric cancer (GC) and colorectal cancer (CRC). METHODS: In this study, we
      included 125 individuals with GC diagnosis, 66 individuals with CRC diagnosis and
      475 cancer-free individuals. All participants resided in the North region of
      Brazil and authorized the use of their samples. The 12 polymorphisms (in CASP8,
      CYP2E1, CYP19A1, IL1A, IL4, MDM2, NFKB1, PAR1, TP53, TYMS, UGT1A1 and XRCC1
      genes) were genotyped in a single PCR for each individual, followed by fragment
      analysis. To avoid misinterpretation due to population substructure, we applied a
      previously developed set of 61 ancestry-informative markers that can also be
      genotyped by multiplex PCR. The statistical analyses were performed in Structure
      v.2.3.4, R environment and SPSS v.20. RESULTS: After statistical analyses with
      the control of confounding factors, such as genetic ancestry, three markers
      (rs79071878 in IL4, rs3730485 in MDM2 and rs28362491 in NFKB1) were positively
      associated with the development of GC. One of these markers (rs28362491) and the
      marker in the UGT1A1 gene (rs8175347) were positively associated with the
      development of CRC. Therefore, we investigated whether the joint presence of the
      deleterious alleles of each marker could affect the development of cancer and we
      obtained positive results in all analyses. Carriers of the combination of alleles
      RP1 + DEL (rs79071878 and rs28361491, respectively) are at 10-times greater risk
      of developing GC than carriers of other combinations. Similarly, carriers of the
      combination of DEL + RARE (rs283628 and rs8175347) are at about 12-times greater
      risk of developing CRC than carriers of other combinations. CONCLUSION: These
      findings are important for the comprehension of gastric and CRC development,
      particularly in highly admixed populations, such as the Brazilian population.

PMID- 29358862
TI  - Childhood-onset inflammatory bowel diseases associated with mutation of Wiskott
      Aldrich syndrome protein gene.
AB  - AIM: To screen primary immunodeficiency, Wiskott-Aldrich syndrome (WAS), and
      chronic granulomatous disease (CGD) among children with inflammatory bowel
      disease (IBD). METHODS: This was a single-center retrospective study. Eighteen
      children with IBD were investigated. We analyzed their expression of Wiskott
      Aldrich syndrome protein (WASP) in lymphocytes and superoxide generation in
      phagocytes using flow cytometry. When the expression of WASP or superoxide
      generation was low or absent, we performed genetic analysis to determine the
      cause of this. RESULTS: Eighteen patients were classified as having ulcerative
      colitis (n = 10), Crohn's disease (n = 5), or IBD-unclassified (n = 3). In total,
      three patients revealed low expression of WASP associated with a WAS gene c.1378
      C>T p.Pro460Ser mutation, which has previously been reported as a pathogenic
      mutation in WAS and X-linked thrombocytopenia. However, with respect to the major
      symptoms of WAS, none of these three patients showed either thrombocytopenia or
      increased susceptibility to infection, but one patient showed generalized eczema.
      No CGD patients were discovered in this study. CONCLUSION: Despite the lack of
      typical clinical manifestations of WAS, low expression of WASP could be
      associated with the pathogenesis of a subtype of IBD patients.

PMID- 29358863
TI  - Comparison of totally laparoscopic total gastrectomy using an endoscopic linear
      stapler with laparoscopic-assisted total gastrectomy using a circular stapler in
      patients with gastric cancer: A single-center experience.
AB  - AIM: To evaluate the safety and efficacy of totally laparoscopic total
      gastrectomy (TLTG) with esophagojejunostomy using a linear stapler compared with
      laparoscopic-assisted total gastrectomy (LATG) using a circular stapler in
      gastric cancer patients. METHODS: We retrospectively reviewed 687 patients who
      underwent laparoscopic total gastrectomy for gastric cancer at a single
      institution from August 2008 to August 2014. The patients were divided into two
      groups according to the type of operation: 421 patients underwent TLTG and 266
      underwent LATG. Clinicopathologic characteristics and surgical outcomes in the
      two groups were compared and analyzed. RESULTS: The TLTG group had higher mean
      ages at the time of operation (57.78 +/- 11.20 years and 55.69 +/- 11.96 years, P
      = 0.020) and more histories of abdominal surgery (20.2% and 12.4%, P = 0.008)
      compared with the LATG group. Surgical outcomes such as intraoperative and
      postoperative transfusions, combined operations, pain scores and administration
      of analgesics, and complications were similar between the two groups. However,
      compared with the LATG group, the TLTG group required a shorter operation time
      (149 min vs 170 min, P < 0.001), had lower postoperative hematocrit change (3.49%
      vs 4.04%, P = 0.002), less intraoperative events (3.1% vs 10.2%, P < 0.001), less
      intraoperative anastomosis events (2.4% vs 7.1%, P = 0.003), faster postoperative
      recovery such as median time to first flatus (3.30 d vs 3.60 d, P < 0.001),
      faster median commencement of soft diet (4.30 d vs 4.60 d, P < 0.001) and shorter
      length of postoperative hospital stay (6.75 d vs 7.02 d, P = 0.005). CONCLUSION:
      The intracorporeal method for reconstruction of esophagojejunostomy using a
      linear stapler may be considered a feasible procedure comparing with
      extracorporeal anastomosis using circular stapler because TLTG is simpler and
      more straightforward than LATG. Therefore, TLTG can be recommended as an
      appropriate procedure for gastric cancer.

PMID- 29358864
TI  - Prognostic significance of pretreatment serum carcinoembryonic antigen levels in
      gastric cancer with pathological lymph node-negative: A large sample single
      center retrospective study.
AB  - AIM: To assess whether elevated serum carcinoembryonic antigen (CEA) is in the
      inferior prognosis for pathological lymph node-negative (pN0) gastric cancer (GC)
      patients who underwent D2 gastrectomy. METHODS: About 469 pN0 GC patients, who
      received D2 radical gastrectomy were retrospectively analyzed. The X-tile plots
      cut-off point for CEA were 30.02 ng/mL using minimum P-value from log-rank chi2
      statistics, and pN0 GC patients were assigned to two groups: those more than
      30.02 ng/mL (n = 48; CEA-high group) and those less than 30.02 ng/mL (n = 421;
      CEA-low group). Clinicopathologic characteristics were compared using Pearson's
      chi2 or Fisher's exact tests, and survival curves were so manufactured using the
      Kaplan-Meier method. Univariate and multivariate analysis were carried out using
      the logistic regression method. RESULTS: The percentage of vessel carcinoma
      embolus (31.35% vs 17.1%) and advanced GC (T2-4b) (81.25% vs 65.32%) were higher
      in CEA-high group than CEA-low group. The CEA-positive patients had a
      significantly poorer prognosis than the CEA-nagetive patients in terms of overall
      survival (57.74% vs 90.69%, P < 0.05), and no different was found between
      subgroup of T category, differentiation, nerve invasion, and vessel carcinoma
      embolus (all P > 0.05). Multivariate survival analysis showed that CEA (OR =
      4.924), and T category (OR = 2.214) were significant prognostic factors for stage
      pN0 GC (all P < 0.05). Besides, only T category (OR = 1.962) was an independent
      hazard factor in the CEA-high group (P < 0.05). CONCLUSION: Those pretreatment
      serum CEA levels over 30.02 ng/mL on behalf of worse characteristics and
      unfavourable tumor behavior, and a poor prognosis for a nearly doubled risk of
      mortality in GC patients.

PMID- 29358865
TI  - Fecal microbiota transplantation induces remission of infantile allergic colitis
      through gut microbiota re-establishment.
AB  - AIM: To investigate the impact of fecal microbiota transplantation (FMT)
      treatment on allergic colitis (AC) and gut microbiota (GM). METHODS: We selected
      a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not
      relieve completely after routine therapy or cannot adhere to the therapy, and
      were free from organ congenital malformations and other contraindications for
      FMT. Qualified donor-derived stools were collected and injected to the AC infants
      via a rectal tube. Clinical outcomes and follow-up observations were noted.
      Stools were collected from ten AC infants before and after FMT, and GM
      composition was assessed for infants and donors using 16S rDNA sequencing
      analysis. RESULTS: After FMT treatment, AC symptoms in 17 infants were relieved
      within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement
      was also detected in the other two AC infants who were lost to follow-up. During
      follow-up, one AC infant suffered from mild eczema and recovered shortly after
      hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them
      (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased
      (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover,
      Firmicutes accounted for the greatest proportion of GM in the patients. At the
      genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4)
      were enriched in some AC infants after FMT treatment, but the relative abundances
      of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and
      Klebsiella (n = 8) decreased dramatically. CONCLUSION: FMT is a safe and
      effective method for treating pediatric patients with AC and restoring GM
      balance.

PMID- 29358866
TI  - Prognostic value of lymph node metastasis in patients with T1-stage colorectal
      cancer from multiple centers in China.
AB  - AIM: To explore the features and prognostic value of lymph node metastasis in
      patients with T1-stage colorectal cancer (CRC). METHODS: In all, 321 cases of T1
      stage CRC were selected from 10132 patients with CRC who received surgical
      therapy in six large-scale hospitals in China and were retrospectively analyzed.
      Univariate and multivariate analyses were performed to analyze the risk factors
      for lymphatic metastasis. A survival analysis was then performed to analyze the
      prognostic value of lymph node metastasis. RESULTS: The occurrence rate of T1
      stage was 3.17% (321/10132); of these patients, the lymph node metastasis rate
      was 8.41% (27/321), and the non-lymph node metastasis rate was 91.59% (294/321).
      Univariate analysis showed that preoperative serum CEA, preoperative serum CA199,
      preoperative serum CA724, vascular invasion, and degree of differentiation were
      associated with lymph node metastasis in T1-stage CRC (P < 0.05 for all).
      Multivariate analysis indicated that preoperative serum CA724, vascular invasion,
      and degree of differentiation were closely related to lymph node metastasis (P <
      0.05 for all). Log-rank survival analysis showed that age, preoperative serum
      CEA, preoperative serum CA199, vascular invasion, degree of differentiation, and
      lymph node metastasis (chi2 = 24.180, P < 0.001) were predictors of 5-year
      overall survival (OS) (P < 0.05 for all). COX regression analysis demonstrated
      that preoperative serum CA199 and lymph node metastasis (HR = 5.117; P < 0.05;
      95%CI: 0.058-0.815) were independent prognostic indicators of 5-year OS in
      patients with T1-stage CRC (P < 0.05 for both). CONCLUSION: The morbidity of T1
      stage CRC was 3.17% for all CRC cases. Preoperative serum CA724, vascular
      invasion, and degree of differentiation are independent risk factors for lymph
      node metastasis. Lymph node metastasis is an independent prognostic factor for OS
      in patients with T1-stage CRC.

PMID- 29358867
TI  - Association between acute pancreatitis and small intestinal bacterial overgrowth
      assessed by hydrogen breath test.
AB  - AIM: To elucidate the effects of small intestinal bacterial overgrowth (SIBO) on
      the severity and complications of acute pancreatitis (AP). METHODS: In total, 208
      patients with AP as defined by the revised Atlanta classification were admitted
      to Xuanwu Hospital of Capital Medical University from 2013 to 2016. All patients
      were admitted within 72 h of AP onset. The hydrogen breath test was performed 7 d
      after AP onset to detect hydrogen production and evaluate the development of
      SIBO. The incidence of SIBO was analyzed in patients with AP of three different
      severity grades. The association between SIBO and complications of AP was also
      assessed. RESULTS: Of the 27 patients with severe AP (SAP), seven (25.92%)
      developed SIBO. Of the 86 patients with moderately severe AP (MSAP), 22 (25.58%)
      developed SIBO. Of the 95 patients with mild AP (MAP), eight (8.42%) developed
      SIBO. There were significant differences in the rates of SIBO among patients with
      AP of different severities. Additionally, more severe AP was associated with
      higher rates of SIBO positivity (P < 0.05). SIBO in patients with AP mainly
      occurred within 72 h of the onset of AP. The incidence of organ failure was
      significantly higher in patients with SIBO than in those without (P < 0.05).
      CONCLUSION: SIBO occurs more frequently in patients with MSAP or SAP than in
      those with MAP, usually <= 72 h after AP onset. Additionally, SIBO is associated
      with organ failure.

PMID- 29358868
TI  - Endoscopic papillary large balloon dilatation with sphincterotomy is safe and
      effective for biliary stone removal independent of timing and size of
      sphincterotomy.
AB  - AIM: To describe the efficacy and safety of endoscopic papillary large balloon
      dilatation (EPLBD) in the management of bile duct stones in a Western population.
      METHODS: Data was collected from the endoscopic retrograde
      cholangiopancreatography (ERCP) and Radiology electronic database along with a
      review of case notes over a period of six years from 1st August 2009 to 31st July
      2015 and incorporated into Microsoft excel. Statistical analyses were performed
      using MedCalc for Windows, version 12.5 (MedCalc Software, Ostend, Belgium).
      Simple statistical applications were applied in order to determine whether
      significant differences exist in comparison groups. We initially used simple
      proportions to describe the study populations. Furthermore, we used chi-square
      test to compare proportions and categorical variables. Non-parametric Mann
      Whitney U-test was applied in order to compare continuous variables. All
      comparisons were deemed to be statistically significant if P values were less
      than 0.05. RESULTS: EPLBD was performed in 229 patients (46 females) with mean
      age of 68 +/- 14.3 years. 115/229 (50%) patients had failed duct clearance at
      previous ERCP referred from elsewhere with standard techniques. Duct clearance at
      the Index* ERCP (1st ERCP at our centre) was 72.5%. Final duct clearance rate was
      98%. EPLBD after fresh sphincterotomy was performed in 81 (35.4%). Median balloon
      size was 13.5 mm (10 - 18). In addition to EPLBD, per-oral cholangioscopy (POC)
      and electrohydraulic lithotripsy (EHL) was performed in 35 (15%) patients at
      index* ERCP. 63 (27.5%) required repeat ERCP for stone clearance. 28 (44.5%)
      required POC and EHL and 11 (17.4%) had repeat EPLBD for complete duct clearance.
      Larger stone size (12.4 mm vs 17.4 mm, P < 0.000001), multiple stones (2, range
      (1-13) vs 3, range (1-12), P < 0.006) and dilated common bile duct (CBD) (12.4 mm
      vs 18.3 mm, P < 0.001) were significant predictors of failed duct clearance at
      index ERCP. 47 patients (20%) had ampullary or peri-ampullary diverticula.
      Procedure related adverse events included 2 cases of bleeding and pancreatitis
      (0.87%) each. CONCLUSION: EPLBD is a safe and effective technique for CBDS
      removal. There is no difference in outcomes whether it is performed at the time
      of sphincterotomy or at a later procedure or whether there is a full or limited
      sphincterotomy.

PMID- 29358869
TI  - Person-centered endoscopy safety checklist: Development, implementation, and
      evaluation.
AB  - AIM: To describe the development and implementation of a person-centered
      endoscopy safety checklist and to evaluate the effects of a "checklist
      intervention". METHODS: The checklist, based on previously published safety
      checklists, was developed and locally adapted, taking patient safety aspects into
      consideration and using a person-centered approach. This novel checklist was
      introduced to the staff of an endoscopy unit at a Stockholm University Hospital
      during half-day seminars and team training sessions. Structured observations of
      the endoscopy team's performance were conducted before and after the introduction
      of the checklist. In addition, questionnaires focusing on patient participation,
      collaboration climate, and patient safety issues were collected from patients and
      staff. RESULTS: A person-centered safety checklist was developed and introduced
      by a multi-professional group in the endoscopy unit. A statistically significant
      increase in accurate patient identity verification by the physicians was noted
      (from 0% at baseline to 87% after 10 mo, P < 0.001), and remained high among
      nurses (93% at baseline vs 96% after 10 mo, P = nonsignificant). Observations
      indicated that the professional staff made frequent attempts to use the
      checklist, but compliance was suboptimal: All items in the observed nurse-led
      "summaries" were included in 56% of these interactions, and physicians
      participated by directly facing the patient in 50% of the interactions. On the
      questionnaires administered to the staff, items regarding collaboration and the
      importance of patient participation were rated more highly after the introduction
      of the checklist, but this did not result in statistical significance (P = 0.07/P
      = 0.08). The patients rated almost all items as very high both before and after
      the introduction of the checklist; hence, no statistical difference was noted.
      CONCLUSION: The intervention led to increased patient identity verification by
      physicians - a patient safety improvement. Clear evidence of enhanced person
      centeredness or team work was not found.

PMID- 29358870
TI  - Multicenter, randomized study to optimize bowel preparation for colon capsule
      endoscopy.
AB  - AIM: To assess the cleansing efficacy and safety of a new Colon capsule endoscopy
      (CCE) bowel preparation regimen. METHODS: This was a multicenter, prospective,
      randomized, controlled study comparing two CCE regimens. Subjects were
      asymptomatic and average risk for colorectal cancer. The second generation CCE
      system (PillCam(r) COLON 2; Medtronic, Yoqneam, Israel) was utilized. Preparation
      regimens differed in the 1st and 2nd boosts with the Study regimen using oral
      sulfate solution (89 mL) with diatrizoate meglumine and diatrizoate sodium
      solution ("diatrizoate solution") (boost 1 = 60 mL, boost 2 = 30 mL) and the
      Control regimen oral sulfate solution (89 mL) alone. The primary outcome was
      overall and segmental colon cleansing. Secondary outcomes included safety, polyp
      detection, colonic transit, CCE completion and capsule excretion <= 12 h.
      RESULTS: Both regimens had similar cleansing efficacy for the whole colon
      (Adequate: Study = 75.9%, Control = 77.3%; P = 0.88) and individual segments. In
      the Study group, CCE completion was superior (Study = 90.9%, Control = 76.9%; P =
      0.048) and colonic transit was more often < 40 min (Study = 21.8%, Control = 4%;
      P = 0.0073). More Study regimen subjects experienced adverse events (Study =
      19.4%, Control = 3.4%; P = 0.0061), and this difference did not appear related to
      diatrizoate solution. Adverse events were primarily gastrointestinal in nature
      and no serious adverse events related either to the bowel preparation regimen or
      the capsule were observed. There was a trend toward higher polyp detection with
      the Study regimen, but this did not achieve statistical significance for any size
      category. Mean transit time through the entire gastrointestinal tract, from
      ingestion to excretion, was shorter with the Study regimen while mean colonic
      transit times were similar for both study groups. CONCLUSION: A CCE bowel
      preparation regimen using oral sulfate solution and diatrizoate solution as a
      boost agent is effective, safe, and achieved superior CCE completion.

PMID- 29358872
TI  - Psychiatric morbidity after surgery for inflammatory bowel disease: A systematic
      review.
AB  - AIM: To examine the evidence about psychiatric morbidity after inflammatory bowel
      disease (IBD)-related surgery. METHODS: PRISMA guidelines were followed and a
      protocol was published at PROSPERO (CRD42016037600). Inclusion criteria were
      studies describing patients with inflammatory bowel disease undergoing surgery
      and their risk of developing psychiatric disorder. RESULTS: Twelve studies
      (including 4340 patients) were eligible. All studies were non-randomized and most
      had high risk of bias. Patients operated for inflammatory bowel disease had an
      increased risk of developing depression, compared with surgical patients with
      diverticulitis or inguinal hernia, but not cancer. In addition, patients with
      Crohn's disease had higher risk of depression after surgery compared with non
      surgical patients. Patients with ulcerative colitis had higher risk of anxiety
      after surgery compared with surgical colorectal cancer patients. Charlson
      comorbidity score more than three and female gender were independent predictors
      for depression and anxiety following surgery. CONCLUSION: The review cannot give
      any clear answer to the risks of psychiatric morbidity after surgery for IBD
      studies with the lowest risk of bias indicated an increased risk of depression
      among surgical patients with Crohn's disease and increased risk of anxiety among
      patients with ulcerative colitis.

PMID- 29358871
TI  - Fusobacterium's link to colorectal neoplasia sequenced: A systematic review and
      future insights.
AB  - AIM: To critically evaluate previous scientific evidence on Fusobacterium's role
      in colorectal neoplasia development. METHODS: Two independent investigators
      systematically reviewed all original scientific articles published between
      January, 2000, and July, 2017, using PubMed, EMBASE, and MEDLINE. A total of 355
      articles were screened at the abstract level. Of these, only original scientific
      human, animal, and in vitro studies investigating Fusobacterium and its
      relationship with colorectal cancer (CRC) were included in the analysis.
      Abstracts, review articles, studies investigating other colonic diseases, and
      studies written in other languages than English were excluded from our analysis.
      Ninety articles were included after removing duplicates, resolving disagreements
      between the two reviewers, and applying the above criteria. RESULTS: Studies have
      consistently identified positive associations between Fusobacterium, especially
      Fusobacterium nucleatum (F. nucleatum), and CRC. Stronger associations were seen
      in CRCs proximal to the splenic flexure and CpG island methylator phenotype
      (CIMP)-high CRCs. There was evidence of temporality and a biological gradient,
      with increased F. nucleatum DNA detection and quantity along the traditional
      adenoma-carcinoma sequence and in CIMP-high CRC precursors. Diet may have a
      differential impact on colonic F. nucleatum enrichment; evidence suggests that
      high fiber diet may reduce the risk of a subset of CRCs that are F. nucleatum DNA
      positive. Data also suggest shorter CRC and disease-specific survival with
      increased amount of F. nucleatum DNA in CRC tissue. The pathophysiology of
      enrichment of F. nucleatum and other Fusobacterium species in colonic tissue is
      unclear; however, the virulence factors and changes to the local colonic
      environment with disruption of the protective mucus layer may contribute. The
      presence of a host lectin (Gal-GalNAc) in the colonic epithelium may also mediate
      F. nucleatum attachment to CRC and precursors through interaction with an F.
      nucleatum protein, fibroblast activation protein 2 (FAP2). The clinical
      significance of detection or enrichment of Fusobacterium in colorectal neoplasia
      is ambiguous, but data suggest a procarcinogenic effect of F. nucleatum, likely
      due to activation of oncogenic and inflammatory pathways and modulation of the
      tumor immune environment. This is hypothesized to be mediated by certain F.
      nucleatum strains carrying invasive properties and virulence factors such as FadA
      and FAP. CONCLUSION: Evidence suggests a potential active role of Fusobacterium,
      specifically F. nucleatum, in CRC. Future prospective and experimental human
      studies would fill an important gap in this literature.

PMID- 29358873
TI  - Stricturing Crohn's disease-like colitis in a patient treated with belatacept.
AB  - Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) modifying agents have been
      involved in the development of intestinal inflammation, especially therapeutic
      monoclonal antibodies directed against CTLA-4. Here we report the appearance of a
      severe stricturing Crohn's disease-like colitis in a patient with a kidney
      allograft who was treated with belatacept, a recombinant CTLA-4-Ig fusion
      protein.

PMID- 29358874
TI  - Emphysematous pancreatitis associated with penetrating duodenal ulcer.
AB  - In the "proton pump inhibitors era", a penetrating peptic ulcer (PPU) represents
      an exceptional cause of abdominal pain, and was more frequently observed in the
      past where there was not an effective antacid treatment. Ulcer-induced
      pancreatitis is very rare, too, and manifests with persistent, intense pain
      radiating to the back. A mild to severe pancreatitis with peripancreatic fluid
      collection can be observed at imaging. However, only a few cases of association
      between PPU and emphysematous pancreatitis (EP) have been published in the
      literature. EP is a rare but potentially fatal form of acute necrotizing
      pancreatitis in which gas grows in and outside the pancreas, and typically
      involves the whole parenchyma in diabetic individuals. Here we report an
      extremely rare case of a duodenal ulcer penetrating the pancreas and complicated
      with EP. Unlike the classic form of EP, which involves the whole parenchyma and
      has a poor prognosis, we found that the emphysematous involvement of the pancreas
      by PPU has a benign course if a conservative therapy is promptly established. Gas
      is confined to the site of penetration, usually the pancreatic head, and ulcers
      most often involve the duodenum.

PMID- 29358875
TI  - Infiltrative xanthogranulomatous cholecystitis mimicking aggressive gallbladder
      carcinoma: A diagnostic and therapeutic dilemma.
AB  - Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic
      cholecystitis. The perioperative findings in aggressive cases may be
      indistinguishable from those of gallbladder or biliary tract carcinomas. Three
      patients presented mass lesions that infiltrated the hepatic hilum, provoked
      biliary dilatation and jaundice, and were indicative of malignancy. Surgical
      excision was performed following oncological principles and included extirpation
      of the gallbladder, extrahepatic bile duct, and hilar lymph nodes, as well as
      partial hepatectomy. Postoperative morbidity was minimal. Surgical pathology
      demonstrated XGC and absence of malignancy in all three cases. All three patients
      are alive and well after years of follow-up. XGC may have such an aggressive
      presentation that carcinoma may only be ruled out on surgical pathology. In such
      cases, the best option may be radical resection following oncological principles
      performed by expert surgeons, in order that postoperative complications may be
      minimized if not avoided altogether.

PMID- 29358876
TI  - Estrogen, estrogen receptors, and hepatocellular carcinoma: Are we there yet?
AB  - A protective role of the sex steroid hormone estrogen in hepatocellular carcinoma
      (HCC) was suggested a few decades ago according to clinical data showing higher
      HCC morbidity and mortality among males. Several recent studies further confirmed
      the anti-cancer effects of estrogen in the liver. However, it remains to be
      identified how to exploit estrogen signalling within clinical settings for HCC
      treatment. There are several unresolved issues related to the estrogen pathway in
      liver cells. The main problems include the absence of a clear understanding of
      which estrogen receptor (ER) isoform is predominantly expressed in normal and
      malignant liver cells, the ER isoform expression difference between males and
      females, and which ER isoform should be targeted when designing HCC therapy. Some
      of those questions were recently addressed by Iyer and co-authors. The current
      editorial review critically analyses the study by Iyer et al (WJG, 2017) that
      investigated the expression of ER subtypes in liver samples collected from
      patients with a healthy liver, hepatitis C virus cirrhosis, and HCC. ER presence
      was evaluated in association with gender, intracellular localization,
      inflammation marker NF-kappaB, and proliferation-related effector cyclin D1. The
      study limitations and advantages are discussed in light of recent advances in the
      HCC and estrogen signalling areas.

PMID- 29358877
TI  - Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and
      clinical application of probiotics and fecal microbiota transplantation.
AB  - Ulcerative colitis (UC) is an inflammatory disease that mainly affects the colon
      and rectum. It is believed that genetic factors, host immune system disorders,
      intestinal microbiota dysbiosis, and environmental factors contribute to the
      pathogenesis of UC. However, studies on the role of intestinal microbiota in the
      pathogenesis of UC have been inconclusive. Studies have shown that probiotics
      improve intestinal mucosa barrier function and immune system function and promote
      secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful
      bacteria in the intestine. Fecal microbiota transplantation (FMT) can reduce
      bowel permeability and thus the severity of disease by increasing the production
      of short-chain fatty acids, especially butyrate, which help maintain the
      integrity of the epithelial barrier. FMT can also restore immune dysbiosis by
      inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and
      production of inflammatory factors. Probiotics and FMT are being increasingly
      used to treat UC, but their use is controversial because of uncertain efficacy.
      Here, we briefly review the role of intestinal microbiota in the pathogenesis and
      treatment of UC.

PMID- 29358878
TI  - Updated review on immune factors in pathogenesis of Crohn's disease.
AB  - Although the incidence of Crohn's disease (CD) in China is not as high as that in
      European and American countries, there has been a clear increasing trend in
      recent years. Little is known about its pathogenesis, cause of deferment, and the
      range of complications associated with the disease. Local and international
      scholars have presented many hypotheses about CD pathogenesis based on
      experimental and clinical studies, including genetic susceptibility, immune
      function defects, intestinal microflora disorders, delayed hypersensitivity, and
      food antigen stimulation. However, the specific mechanism leading to this immune
      imbalance, which causes persistent intestinal mucosal damage, and the source of
      the inflammatory cascade reaction are still unclear. So far, the results of
      research studies differ locally and internationally. This paper presents the most
      current research on immune factors in the pathogenesis of CD.

PMID- 29358879
TI  - Construction of an oesophageal cancer-specific ceRNA network based on miRNA,
      lncRNA, and mRNA expression data.
AB  - AIM: To explore the expression profiles of microRNAs (miRNAs), long non-coding
      RNAs (lncRNAs), and mRNAs in oesophageal squamous cell carcinoma (ESCC) in order
      to construct an oesophageal cancer-specific competing endogenous RNA (ceRNA)
      network. METHODS: In this work, the expression data of miRNAs, lncRNAs, and mRNAs
      in ESCC were obtained. An oesophageal cancer-specific ceRNA network was then
      constructed and investigated. RESULTS: CeRNAs have the ability to reduce the
      targeting activity of miRNAs, leading to the de-repression of specific mRNAs with
      common miRNA response elements. CeRNA interactions have a critical effect in gene
      regulation and cancer development. CONCLUSION: This study suggests a novel
      perspective on potential oesophageal cancer mechanisms as well as novel pathways
      for modulating ceRNA networks for treating cancers.

PMID- 29358881
TI  - Increased intestinal mucosal leptin levels in patients with diarrhea-predominant
      irritable bowel syndrome.
AB  - AIM: To measure the leptin levels in patients with diarrhea-predominant irritable
      bowel syndrome (IBS-D) and analyze the relationship of leptin with clinical
      features, visceral sensitivity, mast cells, and nerve fibers. METHODS: Forty-two
      patients with IBS-D fulfilling the Rome III criteria and 20 age- and sex-matched
      healthy controls underwent clinical and psychological evaluations using validated
      questionnaires (including IBS Symptom Severity Scale, IBS-specific Quality of
      Life, Hamilton Anxiety Scale, and Hamilton Depression Scale), along with
      colonoscopy, colonic mucosal biopsy, and visceral sensitivity testing. Serum
      leptin levels were assayed using enzyme-linked immunosorbent assay. Mucosal
      leptin expression and localization were evaluated using immunohistochemistry and
      immunofluorescence. Mucosal leptin mRNA levels were quantified using quantitative
      real-time reverse transcription polymerase chain reaction. Mast cell counts and
      activation rates were investigated by toluidine blue staining. Correlation
      analyses between these parameters were performed. RESULTS: There were no
      statistically significant differences in age, gender, or body mass index between
      the IBS-D group and the control group. The median IBS Symptom Severity Scale
      score in the IBS-D group was 225.0 (range, 100-475). IBS-D patients had
      significantly increased anxiety [IBS-D: median, 6.5; interquartile range (IQR),
      3.3; control: median, 2.0; IQR, 2.0; P < 0.001] and depression (IBS-D: median,
      7.0; IQR, 3.0; control: median, 3.0; IQR, 2.0; P < 0.001) scores. IBS-D patients
      had significantly lower first sensation threshold (IBS-D: median, 50.6; IQR,
      25.9; control: median, 80.5; IQR, 18.6; P < 0.001), defecation sensation
      threshold (IBS-D: median, 91.5; IQR, 29.3; control: median, 155.0; IQR, 21.1; P <
      0.001) and maximum tolerable threshold (IBS-D: median, 163.2; IQR, 71.2; control:
      median, 226.2; IQR, 39.3; P < 0.001). Mucosal leptin expression, as reflected by
      integrated optical density (IBS-D: median, 4424.71; IQR, 4533.63; control:
      median, 933.65; IQR, 888.10; P < 0.001), leptin mRNA expression (IBS-D: median,
      1.1226; IQR, 1.6351; control: median, 0.8947; IQR, 0.4595; P = 0.009), and mast
      cell activation rate (IBS-D: median, 71.2%; IQR, 12.9%; control group: median,
      59.4%; IQR, 18.88%; P < 0.001) were significantly increased in IBS-D patients.
      The colocalization of leptin and leptin receptors was observed on mast cells and
      PGP9.5-positive nerve fibers in the intestinal mucosa. Also, leptin expression
      was positively correlated with anxiety, depression, and the mast cell activation
      rate, but negatively correlated with the defecation sensation threshold and the
      maximum tolerance threshold during visceral sensitivity testing (adjusted P <
      0.0038). CONCLUSION: Increased levels of mucosal leptin may interact with mast
      cells and the nervous system to contribute to the pathogenesis of IBS-D.

PMID- 29358880
TI  - Emodin and baicalein inhibit sodium taurocholate-induced vacuole formation in
      pancreatic acinar cells.
AB  - AIM: To investigate the effects of combined use of emodin and baicalein (CEB) at
      the cellular and organism levels in severe acute pancreatitis (SAP) and explore
      the underlying mechanism. METHODS: SAP was induced by retrograde infusion of 5%
      sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic
      histopathology score, serum amylase activity, and levels of tumour necrosis
      factor alpha (TNF-alpha), interleukin 6 (IL-6), and IL-10 were determined to
      assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar
      cells were isolated from healthy male SD rats using collagenase. The cell
      viability, cell ultrastructure, intracellular free Ca2+ concentration, and
      inositol (1,4,5)-trisphosphate receptor (IP3R) expression were investigated to
      assess the mechanism of CEB. RESULTS: Pancreatic histopathology score (2.07 +/-
      1.20 vs 6.84 +/- 1.13, P < 0.05) and serum amylase activity (2866.2 +/- 617.7 vs
      5241.3 +/- 1410.0, P < 0.05) were significantly decreased in the CEB (three
      doses) treatment group compared with the SAP group (2.07 +/- 1.20 vs 6.84 +/-
      1.13, P < 0.05). CEB dose-dependently reduced the levels of the pro-inflammatory
      cytokines IL-6 (466.82 +/- 48.55 vs 603.50 +/- 75.53, P < 0.05) and TNF-alpha
      (108.04 +/- 16.10 vs 215.56 +/- 74.67, P < 0.05) and increased the level of the
      anti-inflammatory cytokine IL-10 (200.96 +/- 50.76 vs 54.18 +/- 6.07, P < 0.05)
      compared with those in the SAP group. CEB increased cell viability, inhibited
      cytosolic Ca2+ concentration, and significantly ameliorated intracellular
      vacuoles and IP3 mRNA expression compared with those in the SAP group (P < 0.05).
      There was a trend towards decreased IP3R protein in the CEB treatment group;
      however, it did not reach statistical significance (P > 0.05). CONCLUSION: These
      results at the cellular and organism levels reflect a preliminary mechanism of
      CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.

PMID- 29358882
TI  - Correlation between smoking habit and surgical outcomes on viral-associated
      hepatocellular carcinomas.
AB  - AIM: To investigate the association between smoking habits and surgical outcomes
      in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) (B-HCC) and
      hepatitis C virus (HCV)-related HCC (C-HCC) and clarify the clinicopathological
      features associated with smoking status in B-HCC and C-HCC patients. METHODS: We
      retrospectively examined the cases of the 341 consecutive patients with viral
      associated HCC (C-HCC, n = 273; B-HCC, n = 68) who underwent curative surgery for
      their primary lesion. We categorized smoking status at the time of surgery into
      never, ex- and current smoker. We analyzed the B-HCC and C-HCC groups'
      clinicopathological features and surgical outcomes, i.e., disease-free survival
      (DFS), overall survival (OS), and disease-specific survival (DSS). Univariate and
      multivariate analyses were performed using a Cox proportional hazards regression
      model. We also performed subset analyses in both patient groups comparing the
      current smokers to the other patients. RESULTS: The multivariate analysis in the
      C-HCC group revealed that current-smoker status was significantly correlated with
      both OS (P = 0.0039) and DSS (P = 0.0416). In the B-HCC patients, no significant
      correlation was observed between current-smoker status and DFS, OS, or DSS in the
      univariate or multivariate analyses. The subset analyses comparing the current
      smokers to the other patients in both the C-HCC and B-HCC groups revealed that
      the current smokers developed HCC at significantly younger ages than the other
      patients irrespective of viral infection status. CONCLUSION: A smoking habit is
      significantly correlated with the overall and disease-specific survivals of
      patients with C-HCC. In contrast, the B-HCC patients showed a weak association
      between smoking status and surgical outcomes.

PMID- 29358883
TI  - Safety and efficacy of metallic stent for unresectable distal malignant biliary
      obstruction in elderly patients.
AB  - AIM: To study the safety of insertion of metallic stents in elderly patients with
      unresectable distal malignant biliary obstruction. METHODS: Of 272 patients with
      unresectable distal malignant biliary obstruction, 184 patients under the age of
      80 were classified into Group A, and 88 subjects aged 80 years or more were
      classified into Group B. The safety of metallic stent insertion, metal stent
      patency period, and the obstruction rate were examined in each group. RESULTS: In
      Group B, patients had a significantly worse performance status, high blood
      pressure, heart disease, cerebrovascular disease, and dementia; besides the rate
      of patients orally administered antiplatelet drugs or anticoagulants tended to be
      higher (P < 0.05). Metallic stents were successfully inserted in all patients.
      The median patency period was 265.000 +/- 26.779 (1-965) d; 252.000 +/- 35.998 (1
      618) d in Group A and 269.000 +/- 47.885 (1-965) d in Group B, with no
      significant difference between the two groups. Metallic stent obstruction
      occurred in 82 of the 272 (30.15%) patients; in 53/184 (28.80%) patients in Group
      A and in 29/88 (32.95%) of those in Group B, showing no significant difference
      between the two groups. Procedural accidents due to metal stent insertion
      occurred in 24/272 (8.8%) patients; in 17/184 (9.2%) of patients in Group A and
      in 7/88 (8.0%) of those in Group B, with no significant difference between the
      two groups, either. CONCLUSION: These results suggested that metallic stents can
      be safely inserted to treat unresectable distal malignant biliary obstruction
      even in elderly patients aged 80 years or more.

PMID- 29358884
TI  - Short- and long-term outcomes following laparoscopic vs open surgery for
      pathological T4 colorectal cancer: 10 years of experience in a single center.
AB  - AIM: To evaluate the short-term and long-term outcomes following laparoscopic vs
      open surgery for pathological T4 (pT4) colorectal cancer. METHODS: We
      retrospectively analyzed the short- and long-term outcomes of proven pT4
      colorectal cancer patients who underwent complete resection by laparoscopic or
      open surgery from 2006 to 2015 at Guangdong General Hospital. RESULTS: A total of
      211 pT4 colorectal cancer patients were included in this analysis, including 101
      cases in the laparoscopy (LAP) group and 110 cases in the open surgery (OPEN)
      group [including 15 (12.9%) cases of conversion to open surgery]. Clinical
      information (age, gender, body mass index, comorbidities, American Society of
      Anesthesiologists score, etc.) did not differ between the two groups. In terms of
      blood loss, postoperative complications and rate of recovery, the LAP group
      performed significantly more favorably (P < 0.05). With regard to pT4a/b and
      combined organ resection, there were significantly more cases in the OPEN group
      (P < 0.05). The 3- and 5-year overall survival rates were 74.9% and 60.5%,
      respectively, for the LAP group and 62.4% and 46.5%, respectively, for the OPEN
      group (P = 0.060). The 3- and 5-year disease-free survival rates were 68.0% and
      57.3%, respectively, for the LAP group and 55.8% and 39.8%, respectively, for the
      OPEN group (P = 0.053). Multivariate analysis showed that IIIB/IIIC stage, lymph
      node status, and CA19-9 were significant predictors of overall survival. PT4a/b,
      IIIC stage, histological subtypes, CA19-9, and adjuvant chemotherapy were
      independent factors affecting disease-free survival. CONCLUSION: Laparoscopy is
      safely used in the treatment of pT4 colorectal cancer while offering advantages
      of minimal invasiveness and faster recovery. Laparoscopy is able to achieve good
      oncologic outcomes similar to those of open surgery. We recommend that
      laparoscopy be carried out in experienced centers. It is still required to screen
      the appropriate cases for laparoscopic surgery, optimize the preoperative
      diagnosis process, and reduce the conversion rate. Multi-center, prospective, and
      large-sample studies are required to assess these issues.

PMID- 29358885
TI  - Differential analysis of lymph node metastasis in histological mixed-type early
      gastric carcinoma in the mucosa and submucosa.
AB  - AIM: To investigate the relationship between histological mixed-type of early
      gastric cancer (EGC) in the mucosa and submucosa and lymph node metastasis (LNM).
      METHODS: This study included 298 patients who underwent gastrectomy for EGC
      between 2005 and 2012. Enrolled lesions were divided into groups of pure
      differentiated (pure D), pure undifferentiated (pure U), and mixed-type according
      to the proportion of the differentiated and undifferentiated components observed
      under a microscope. We reviewed the clinicopathological features, including age,
      sex, location, size, gross type, lymphovascular invasion, ulceration, and LNM,
      among the three groups. Furthermore, we evaluated the predictors of LNM in the
      mucosa-confined EGC. RESULTS: Of the 298 patients, 165 (55.4%) had mucosa
      confined EGC and 133 (44.6%) had submucosa-invasive EGC. Only 13 (7.9%) cases of
      mucosa-confined EGC and 30 (22.6%) cases of submucosa-invasive EGC were observed
      to have LNM. The submucosal invasion (OR = 4.58, 95%CI: 1.23-16.97, P = 0.023),
      pure U type (OR = 4.97, 95%CI: 1.21-20.39, P = 0.026), and mixed-type (OR = 5.84,
      95%CI: 1.05-32.61, P = 0.044) were independent risk factors for LNM in EGC. The
      rate of LNM in mucosa-confined EGC was higher in the mixed-type group (P = 0.012)
      and pure U group (P = 0.010) than in the pure D group, but no significant
      difference was found between the mixed-type group and pure U group (P = 0.739).
      Similarly, the rate of LNM in the submucosa-invasive EGC was higher in the mixed
      type (P = 0.012) and pure U group (P = 0.009) than in the pure D group but was
      not significantly different between the mixed-type and pure U group (P = 0.375).
      Multivariate logistic analysis showed that only female sex (OR = 5.83, 95%CI:
      1.64-20.70, P = 0.028) and presence of lymphovascular invasion (OR = 13.18,
      95%CI: 1.39-125.30, P = 0.020) were independent risk factors for LNM in mucosa
      confined EGC, while histological type was not an independent risk factor for LNM
      in mucosa-confined EGC (P = 0.106). CONCLUSION: For mucosal EGC, histological
      mixed-type is not an independent risk factor for LNM and could be managed in the
      same way as the undifferentiated type.

PMID- 29358887
TI  - Surgical specimen extraction via a prophylactic ileostomy procedure: A minimally
      invasive technique for laparoscopic rectal cancer surgery.
AB  - AIM: To retrospectively evaluate the safety and feasibility of surgical specimen
      extraction via a prophylactic ileostomy procedure in patient with rectal cancer.
      METHODS: We systematically reviewed 331 consecutive patients who underwent
      laparoscopic anterior resection for rectal cancer and prophylactic ileostomy in
      our institution from June 2010 to October 2016, including 155 patients who
      underwent specimen extraction via a prophylactic ileostomy procedure
      (experimental group), and 176 patients who underwent specimen extraction via a
      small lower abdominal incision (control group). Clinical data were collected from
      both groups and statistically analyzed. RESULTS: The two groups were matched in
      clinical characteristics and pathological outcomes. However, mean operative time
      was significantly shorter in the experimental group compared to the control group
      (161.3 +/- 21.5 min vs 168.8 +/- 20.5 min; P = 0.001). Mean estimated blood loss
      was significantly less in the experimental group (77.4 +/- 30.7 mL vs 85.9 +/-
      35.5 mL; P = 0.020). The pain reported by patients during the first two days
      after surgery was significantly less in the experimental group than in the
      control group. No wound infections occurred in the experimental group, but 4.0%
      of the controls developed wound infections (P = 0.016). The estimated 5-year
      disease-free survival and overall survival rate were similar between the two
      groups. CONCLUSION: Surgical specimen extraction via a prophylactic ileostomy
      procedure represents a secure and feasible approach to laparoscopic rectal cancer
      surgery, and embodies the principle of minimally invasive surgery.

PMID- 29358886
TI  - HLA-DQ: Celiac disease vs inflammatory bowel disease.
AB  - AIM: To determine the genetic predisposition to celiac disease (CeD) in
      inflammatory bowel disease (IBD) patients by quantifying the frequency of CeD
      related human leucocyte antigen (HLA) (HLA-CeD: HLA-DQ2 and -DQ8) in IBD patients
      globally, by type of IBD and gender, and by calculating the protective/risk
      contribution of these haplotypes in the development of the IBD disease. METHODS:
      We conducted a prospective study with IBD patients from our Unit. Clinical
      information was gathered and blood was tested for HLA-CeD. The control group was
      made up of unrelated Valencian organ donors. RESULTS: 1034 subjects were
      analyzed: 457 IBD [207 ulcerative coliti (UC) and 250 Crohn's disease (CD)]
      patients and 577 healthy controls. 39% of the controls and 34% of the patients
      had HLA-CeD (P = 0.0852). HLA-DQ2 was less frequent in UC patients (P = 0.0287),
      and HLA-DQ8 in CD (P = 0.0217). In women with UC, the frequency of DQ2.5cis
      (DQB1*02:01-DQA1*05:01) was reduced >= 50% [P = 0.0344; preventive fraction (PF)
      = 13%]. PFs (7%-14%) were obtained with all HLA-CeD haplotypes. HLA DQB1*02:02
      DQA1*02:01 (HLA-DQ2.2) was more frequent in CD patients with respect to controls
      (P = 0.001) and UC patients (etiological fraction = 15%). CONCLUSION: HLA-CeD is
      not more frequent in IBD patients, with an even lower frequency of HLA-DQ2 and 
      DQ8 in UC and CD respectively. HLA-DQ2.5 confers protection from the development
      of UC, especially in women, and HLA-DQ8 does so for the appearance of CD. HLA
      DQ2.2 is present in 34% of the CD patients and may constitute a genetic risk
      factor for CD development.

PMID- 29358888
TI  - Characterization of biofilms in biliary stents and potential factors involved in
      occlusion.
AB  - AIM: To quantify the components in biofilms and analyze the predisposing factors
      involved in occlusion of biliary stents. METHODS: In a prospective study
      conducted from April 2011 to March 2014 at a tertiary care hospital, all
      consecutive patients who required endoscopic biliary stent exchange/removal were
      included. Etiology of the biliary disease was diagnosed by imaging, cytology and
      on follow-up. Clinical details of patients with biliary stent retrieval were
      noted. All extracted stents were collected in sterile containers and immediately
      processed for quantification of biofilm proteins and polysaccharides. Molecular
      identification of commonly known and unknown bacteria was performed by polymerase
      chain reaction and density gradient gel electrophoresis methods. RESULTS: Eighty
      one patients (41 males) with age range of 20-86 years were studied. The
      underlying causes for stent insertion were bile duct stones (n = 46; 56.8%)
      benign stricture (n = 29; 35.8%) and malignancy (n = 6; 7.4%) with cholangitis in
      50 (61.7%) patients. The retrieved stent sizes were 7 Fr (n = 62; 76.5%) and 10
      Fr (n = 19; 23.5%) with 65 days median insertion duration. Polybacterial
      consortia were detected in 90.1% of the stents. The most common bacteria
      identified by polymerase chain reaction alone and/or sequencing were Pseudomonas
      (n = 38), Citrobacter (n = 23), Klebsiella (n = 22), Staphylococcus (n = 20),
      Serratia (n = 16), Escherichia coli (n = 14), Streptococcus (n = 13),
      Enterococcus (n = 13), Aeromonas (n = 12), Proteus (n = 10) and Enterobacter (n =
      9). Protein concentration according to gender (0.547 +/- 0.242 mg/mL vs 0.458 +/-
      0.259 mg/mL; P = 0.115) as well as age > 60 years and < 60 years (0.468 +/- 0.295
      mg/mL vs 0.386 +/- 0.238 mg/mL; P = 0.205) was non-significant. However,
      polysaccharide concentration was significant both according to gender (0.052 +/-
      0.021 mg/mL vs 0.049 +/- 0.016 mg/mL; P < 0.0001) and age (0.051 +/- 0.026 mg/mL
      vs 0.038 +/- 0.016 mg/mL; P < 0.011). Protein concentration in the biofilm was
      significantly higher (0.555 +/- 0.225 mg/mL vs 0.419 +/- 0.276 mg/mL; P = 0.018)
      in patients with cholangitis, lower (0.356 +/- 0.252 mg/mL vs 0.541 +/- 0.238
      mg/mL; P = 0.005) in the 10 Fr group than the 7 Fr group, and significantly
      higher (0.609 +/- 0.240 mg/mL vs 0.476 +/- 0.251 mg/mL; P = 0.060) in stents of
      >= 6 mo of indwelling time. However presence/absence of cholangitis, size of
      stent, indication of stent insertion and indwelling time did not affect the
      quantity of polysaccharide concentration. CONCLUSION: Plastic stents retrieved
      from patients with biliary tract disease showed polymicrobial organisms with
      higher protein content among patients with cholangitis and those with smaller
      diameter stents. Longer indwelling duration had more biofilm formation.

PMID- 29358889
TI  - Systematic review of colorectal cancer screening guidelines for average-risk
      adults: Summarizing the current global recommendations.
AB  - AIM: To summarize and compare worldwide colorectal cancer (CRC) screening
      recommendations in order to identify similarities and disparities. METHODS: A
      systematic literature search was performed using MEDLINE, EMBASE, Scopus, CENTRAL
      and ISI Web of knowledge identifying all average-risk CRC screening guideline
      publications within the last ten years and/or position statements published in
      the last 2 years. In addition, a hand-search of the webpages of National
      Gastroenterology Society websites, the National Guideline Clearinghouse, the BMJ
      Clinical Evidence website, Google and Google Scholar was performed. RESULTS:
      Fifteen guidelines were identified. Six guidelines were published in North
      America, four in Europe, four in Asia and one from the World Gastroenterology
      Organization. The majority of guidelines recommend screening average-risk
      individuals between ages 50 and 75 using colonoscopy (every 10 years), or
      flexible sigmoidoscopy (FS, every 5 years) or fecal occult blood test (FOBT,
      mainly the Fecal Immunochemical Test, annually or biennially). Disparities
      throughout the different guidelines are found relating to the use of colonoscopy,
      rank order between test, screening intervals and optimal age ranges for
      screening. CONCLUSION: Average risk individuals between 50 and 75 years should
      undergo CRC screening. Recommendations for optimal surveillance intervals,
      preferred tests/test cascade as well as the optimal timing when to start and stop
      screening differ regionally and should be considered for clinical decision
      making. Furthermore, local resource availability and patient preferences are
      important to increase CRC screening uptake, as any screening is better than none.

PMID- 29358891
TI  - Long-term survival after gastrectomy and metastasectomy for gastric cancer with
      synchronous bone metastasis.
AB  - Bone metastasis is a rare event in patients with gastric cancer, but pathologic
      fracture, paralysis, pain and hematological disorders associated with the bone
      metastasis may influence the quality of life. We report herein the case of a 53
      year-old man who presented with primary remnant gastric cancer with bone
      metastasis. The patient requested further investigations after detection of a
      metastatic lesion in the 2nd lumbar vertebra during evaluation for back pain that
      had persisted for 3 mo. No other metastatic lesions were detected. He underwent
      total gastrectomy and palliative metastasectomy to aid in reduction of symptoms,
      and he received combination chemotherapy with tegafur (S-1) and cisplatin. The
      patient survived for about 60 mo after surgery. Currently, there is no treatment
      guideline for gastric cancer with bone metastasis, and we believe that
      gastrectomy plus metastasectomy may be an effective therapeutic option for
      improving quality of life and survival in patients with resectable primary
      gastric cancer and bone metastasis.

PMID- 29358890
TI  - Probiotic monotherapy and Helicobacter pylori eradication: A systematic review
      with pooled-data analysis.
AB  - AIM: To define probiotic monotherapy effect on Helicobacter pylori (H. pylori)
      status by performing a systematic review. METHODS: Methods of analysis and
      inclusion criteria were based on PRISMA recommendations. Relevant publications
      were identified by searching PubMed, MEDLINE, Science Direct, and EMBASE. The end
      point was to estimate eradication rate and urea breath test delta value before
      and after probiotic monotherapy across all studies and, overall, with a pooled
      data analysis. Adverse events of probiotic therapy were evaluated. The data were
      expressed as proportions/percentages, and 95%CIs were calculated. For continuous
      variables, we evaluated the weighted mean difference. Odd ratios (ORs) were
      calculated according to the Peto method for the comparison of eradication rates
      between probiotics and placebo. RESULTS: Eleven studies were selected. Probiotics
      eradicated H. pylori in 50 out of 403 cases. The mean weighted eradication rate
      was 14% (95%CI: 2%-25%, P = 0.02). Lactobacilli eradicated the bacterium in 30
      out of 235 patients, with a mean weighted rate of 16% (95%CI: 1%-31%).
      Saccharomyces boulardii achieved eradication in 6 out of 63 patients, with a
      pooled eradication rate of 12% (95%CI: 0%-29%). Multistrain combinations were
      effective in 14 out of 105 patients, with a pooled eradication rate of 14%
      (95%CI: 0%-43%). In the comparison of probiotics vs placebo, we found an OR of
      7.91 in favor of probiotics (95%CI: 2.97-21.05, P < 0.001). Probiotics induced a
      mean reduction in delta values higher than placebo (8.61% with a 95%CI: 5.88
      11.34, vs 0.19% for placebo, P < 0.001). Finally, no significant difference in
      adverse events was found between probiotics and placebo (OR = 1, 95%CI: 0.06
      18.08). CONCLUSION: Probiotics alone show a minimal effect on H. pylori
      clearance, thus suggesting a likely direct role.

PMID- 29358892
TI  - Emergent single-balloon enteroscopy for overt bleeding of small intestinal
      vascular malformation.
AB  - A 28-year-old man presented with anemia symptoms and intermittent tarry stool
      passage for three days. No stigmata of hemorrhage were identified using
      esophagogastroduodenoscopy, ileocolonoscopy, and contrast-enhanced computed
      tomography. He then developed massive tarry stool passage with profound
      hypovolemic shock and hypoxic respiratory failure. Emergent angiography revealed
      active bleeder, probably from the jejunal branches of the superior mesenteric
      artery, but embolization was not performed due to possible subsequent extensive
      bowel ischemia. His airway was secured via endotracheal intubation with
      ventilator support, and emergent antegrade single-balloon enteroscopy was
      performed at 8 h after clinical overt bleeding occurrence; the procedure revealed
      a 2-cm pulsating subepithelial tumor with a protruding blood plug at the distal
      jejunum. Laparoscopic segmental resection of the jejunum with end-to-end
      anastomosis was performed after emergent endoscopic tattooing localization.
      Pathological examination revealed a vascular malformation in the submucosa with
      an organizing thrombus. He was uneventfully discharged 5 d later. This case
      report highlights the benefit of early deep enteroscopy for the treatment of
      small intestinal bleeding.

PMID- 29358894
TI  - A new species of Longicoelotes (Araneae, Agelenidae) from China, with the first
      description of the male of L. kulianganus (Chamberlin, 1924).
AB  - A new Longicoeletes species is described from Jiangxi Province, China: L. geeisp.
      n. (??). In addition, the male of L. kulianganus (Chamberlin, 1924) is described
      for the first time. DNA barcodes of the two species are documented for future use
      and as proof of molecular differences between these species.

PMID- 29358893
TI  - Kinect V2 Performance Assessment in Daily-Life Gestures: Cohort Study on Healthy
      Subjects for a Reference Database for Automated Instrumental Evaluations on
      Neurological Patients.
AB  - Background: The increase of sanitary costs related to poststroke rehabilitation
      requires new sustainable and cost-effective strategies for promoting autonomous
      and dehospitalized motor training. In the Riprendo@Home and Future Home for
      Future Communities research projects, the promising approach of introducing low
      cost technologies that promote home rehabilitation is exploited. In order to
      provide reliable evaluation of patients, a reference database of healthy people's
      performances is required and should consider variability related to healthy
      people performances. Methods: 78 healthy subjects performed several repetitions
      of daily-life gestures, the reaching movement (RM) and hand-to-mouth (HtMM)
      movement with both the dominant and nondominant upper limbs. Movements were
      recorded with a Kinect V2. A synthetic biomechanical protocol based on
      kinematical, dynamical, and motor control parameters was used to assess motor
      performance of the healthy people. The investigation was conducted by clustering
      participants depending on their limb dominancy (right/left), gender
      (male/female), and age (young/middle/senior) as sources of variability. Results:
      Results showed that limb dominancy has minor relevance in affecting RM and HtMM;
      gender has relevance in affecting the HtMM; age has major effect in affecting RM
      and HtMM. Conclusions: An investigation of healthy subjects' upper limb
      performances during daily-life gestures was performed with the Kinect V2 sensor.
      Findings will be the basis for a database of normative data for neurological
      patients' motor evaluation.

PMID- 29358895
TI  - Description of a new species of Alburnus Rafinesque, 1820 (Actinopterygii,
      Cyprinidae, Leuciscinae) from the Kolpa River in the Sava River system (upper
      Danube drainage), with remarks on the geographical distribution of shemayas in
      the Danube.
AB  - Alburnus sava, new species, is described from the Kolpa River. The Kolpa is a
      tributary of the Sava, a major tributary of the Danube River, in the Black Sea
      basin. Alburnus sava is distinguished from its congeners in the Danube drainage,
      A. mento and A. sarmaticus, by having 23-27, usually 24-26, gill rakers; the
      ventral keel usually completely covered by scales (scaleless part maximum 15% of
      the keel length); 15-16, mode 15, branched pectoral-fin rays; the length of the
      gill raker at the junction of the arch limbs 65-70% of the length of the opposite
      outer gill filament; and a relatively long lower jaw (37-40% HL or 112-130%
      interorbital width). Alburnus sava is a large-sized potamadromous shemaya known
      to occur in the entire Sava drainage. The taxonomic status of A. mento and A.
      sarmaticus is confirmed. Alburnus danubicus is discussed and as there are no new
      arguments, it is kept as a valid species. New details on the distribution of
      shemayas in the Danube drainage are presented.

PMID- 29358896
TI  - Corrigenda: Jesovnik A, Schultz TR (2017) Revision of the fungus-farming ant
      genus Sericomyrmex Mayr (Hymenoptera, Formicidae, Myrmicinae). ZooKeys 670: 1
      109. https://doi.org/10.3897/zookeys.670.11839.
AB  - [This corrects the article DOI: 10.3897/zookeys.670.11839.].

PMID- 29358897
TI  - Revision of the ant genus Melophorus (Hymenoptera, Formicidae).
AB  - The fauna of the purely Australian formicine ant genus Melophorus (Hymenoptera:
      Formicidae) is revised. This project involved integrated morphological and
      molecular taxonomy using one mitochondrial gene (COI) and four nuclear genes (AA,
      H3, LR and Wg). Seven major clades were identified and are here designated as the
      M. aeneovirens, M. anderseni, M. biroi, M. fulvihirtus, M. ludius, M. majeri and
      M. potteri species-groups. Within these clades, smaller complexes of similar
      species were also identified and designated species-complexes. The M. ludius
      species-group was identified purely on molecular grounds, as the morphology of
      its members is indistinguishable from typical members of the M. biroi species
      complex within the M. biroi species-group. Most species-complexes sampled were
      also found to be monophyletic. Sequencing generally supported monophyly in taxa
      sampled but some species of the M. fieldi complex and M. biroi were not
      monophyletic and the implications arising from this are discussed in this
      monograph. Based on morphology, ninety-three species are recognized, 73 described
      as new. A further new species (here called 'Species K' [TERC Collection]) is
      noted in the taxonomic list, but is not described in this work. One species is
      removed from Melophorus: M. scipio Forel is here placed provisionally in
      Prolasius. Six species and five subspecies pass into synonymy. Of the full
      species, M. constans Santschi, M. iridescens (Emery) and M. insularis Wheeler are
      synonymized under M. aeneovirens (Lowne), M. pillipes Santschi is synonymized
      under M. turneri Forel, M. marius Forel is synonymized under M. biroi Forel, and
      M. omniparens Forel is synonymized under M. wheeleri Forel. Of the subspecies, M.
      iridescens fraudatrix and M. iridescens froggatti Forel are synonymized under M.
      aeneovirens (Lowne), M. turneri aesopus Forel and M. turneri candidus Santschi
      are synonymized under M. turneri Forel and M. fieldi propinqua Viehmeyer is
      synonymized under M. biroi. Camponotus cowlei Froggatt is reinstated as a junior
      synonym of Melophorus bagoti Lubbock. In addition, the subspecies M. fieldi major
      Forel, M. ludius sulla Forel and M. turneri perthensis Forel are raised to
      species. A key to workers of the genus is supplied. A lectotype is designated for
      M. curtus Forel, M. sulla, and M. turneri.

PMID- 29358898
TI  - Concordance-Assisted Learning for Estimating Optimal Individualized Treatment
      Regimes.
AB  - In this article, we propose a new concordance-assisted learning for estimating
      optimal individualized treatment regimes. We first introduce a type of
      concordance function for prescribing treatment and propose a robust rank
      regression method for estimating the concordance function. We then find treatment
      regimes, up to a threshold, to maximize the concordance function, named
      prescriptive index. Finally, within the class of treatment regimes that maximize
      the concordance function, we find the optimal threshold to maximize the value
      function. We establish the convergence rate and asymptotic normality of the
      proposed estimator for parameters in the prescriptive index. An induced smoothing
      method is developed to estimate the asymptotic variance of the proposed
      estimator. We also establish the n1/3-consistency of the estimated optimal
      threshold and its limiting distribution. In addition, a doubly robust estimator
      of parameters in the prescriptive index is developed under a class of monotonic
      index models. The practical use and effectiveness of the proposed methodology are
      demonstrated by simulation studies and an application to an AIDS data.

PMID- 29358899
TI  - Oxidative Post-Translational Modifications of an Amyloidogenic Immunoglobulin
      Light Chain Protein.
AB  - Immunoglobulin light chain amyloidosis (AL) is a plasma cell disorder
      characterized by overproduction and deposition of monoclonal immunoglobulin (Ig)
      light chains (LC) or variable region fragments as amyloid fibrils in various
      organs and tissues. Much clinical evidence indicates that patients with AL
      amyloidosis sustain cardiomyocyte impairment and suffer from oxidative stress. We
      seek to understand the underlying biochemical pathways whose disruption or
      amplification during sporadic or sustained disease states leads to harmful
      physiological consequences and to determine the detailed structures of
      intermediates and products that serve as signposts for the biochemical changes
      and represent potential biomarkers. In this study, matrix-assisted laser
      desorption/ionization mass spectrometry provided extensive evidence for oxidative
      post-translational modifications (PTMs) of an amyloidogenic Ig LC protein from a
      patient with AL amyloidosis. Some of the tyrosine residues were heavily mono- or
      di-chlorinated. In addition, a novel oxidative conversion to a nitrile moiety was
      observed for many of the terminal aminomethyl groups on lysine side chains. In
      vitro experiments using model peptides, in-solution oxidation, and click
      chemistry demonstrated that hypochlorous acid produced by the myeloperoxidase -
      hydrogen peroxide - chloride system could be responsible for these and other,
      more commonly observed modifications.

PMID- 29358901
TI  - Acoustofluidic waveguides for localized control of acoustic wavefront in
      microfluidics.
AB  - The precise manipulation of acoustic fields in microfluidics is of critical
      importance for the realization of many biomedical applications. Despite the
      tremendous efforts devoted to the field of acoustofluidics during recent years,
      dexterous control, with an arbitrary and complex acoustic wavefront, in a
      prescribed, microscale region is still out of reach. Here, we introduce the
      concept of acoustofluidic waveguide, a three-dimensional compact configuration
      that is capable of locally guiding acoustic waves into a fluidic environment.
      Through comprehensive numerical simulations, we revealed the possibility of
      forming complex field patterns with defined pressure nodes within a highly
      localized, pre-determined region inside the microfluidic chamber. We also
      demonstrated the tunability of the acoustic field profile through controlling the
      size and shape of the waveguide geometry, as well as the operational frequency of
      the acoustic wave. The feasibility of the waveguide concept was experimentally
      verified via microparticle trapping and patterning. Our acoustofluidic
      waveguiding structures can be readily integrated with other microfluidic
      configurations and can be further designed into more complex types of passive
      acoustofluidic devices. The waveguide platform provides a promising alternative
      to current acoustic manipulation techniques and is useful in many applications
      such as single-cell analysis, point-of-care diagnostics, and studies of cell-cell
      interactions.

PMID- 29358900
TI  - Iron Oxide Nanoradiomaterials: Combining Nanoscale Properties with Radioisotopes
      for Enhanced Molecular Imaging.
AB  - The combination of the size-dependent properties of nanomaterials with
      radioisotopes is emerging as a novel tool for molecular imaging. There are
      numerous examples already showing how the controlled synthesis of nanoparticles
      and the incorporation of a radioisotope in the nanostructure offer new features
      beyond the simple addition of different components. Among the different
      nanomaterials, iron oxide-based nanoparticles are the most used in imaging
      because of their versatility. In this review, we will study the different
      radioisotopes for biomedical imaging, how to incorporate them within the
      nanoparticles, and what applications they can be used for. Our focus is directed
      towards what is new in this field, what the nanoparticles can offer to the field
      of nuclear imaging, and the radioisotopes hybridized with nanomaterials for use
      in molecular imaging.

PMID- 29358902
TI  - Pivotal Role of Adenosine Neurotransmission in Restless Legs Syndrome.
AB  - The symptomatology of Restless Legs Syndrome (RLS) includes periodic leg
      movements during sleep (PLMS), dysesthesias, and hyperarousal. Alterations in the
      dopaminergic system, a presynaptic hyperdopaminergic state, seem to be involved
      in PLMS, while alterations in glutamatergic neurotransmission, a presynaptic
      hyperglutamatergic state, seem to be involved in hyperarousal and also PLMS.
      Brain iron deficiency (BID) is well-recognized as a main initial
      pathophysiological mechanism of RLS. BID in rodents have provided a pathogenetic
      model of RLS that recapitulates the biochemical alterations of the dopaminergic
      system of RLS, although without PLMS-like motor abnormalities. On the other hand,
      BID in rodents reproduces the circadian sleep architecture of RLS, indicating the
      model could provide clues for the hyperglutamatergic state in RLS. We recently
      showed that BID in rodents is associated with changes in adenosinergic
      transmission, with downregulation of adenosine A1 receptors (A1R) as the most
      sensitive biochemical finding. It was hypothesized that A1R downregulation leads
      to hypersensitive striatal glutamatergic terminals and facilitation of striatal
      dopamine release. Hypersensitivity of striatal glutamatergic terminals was
      demonstrated by an optogenetic-microdialysis approach in the rodent with BID,
      indicating that it could represent a main pathogenetic factor that leads to PLMS
      in RLS. In fact, the dopaminergic agonists pramipexole and ropinirole and the
      alpha2delta ligand gabapentin, used in the initial symptomatic treatment of RLS,
      completely counteracted optogenetically-induced glutamate release from both
      normal and BID-induced hypersensitive corticostriatal glutamatergic terminals. It
      is a main tenet of this essay that, in RLS, a single alteration in the
      adenosinergic system, downregulation of A1R, disrupts the adenosine-dopamine
      glutamate balance uniquely controlled by adenosine and dopamine receptor
      heteromers in the striatum and also the A1R-mediated inhibitory control of
      glutamatergic neurotransmission in the cortex and other non-striatal brain areas,
      which altogether determine both PLMS and hyperarousal. Since A1R agonists would
      be associated with severe cardiovascular effects, it was hypothesized that
      inhibitors of nucleoside equilibrative transporters, such as dipyridamole, by
      increasing the tonic A1R activation mediated by endogenous adenosine, could
      represent a new alternative therapeutic strategy for RLS. In fact, preliminary
      clinical data indicate that dipyridamole can significantly improve the
      symptomatology of RLS.

PMID- 29358903
TI  - Decoding of Ankle Flexion and Extension from Cortical Current Sources Estimated
      from Non-invasive Brain Activity Recording Methods.
AB  - The classification of ankle movements from non-invasive brain recordings can be
      applied to a brain-computer interface (BCI) to control exoskeletons, prosthesis,
      and functional electrical stimulators for the benefit of patients with walking
      impairments. In this research, ankle flexion and extension tasks at two force
      levels in both legs, were classified from cortical current sources estimated by a
      hierarchical variational Bayesian method, using electroencephalography (EEG) and
      functional magnetic resonance imaging (fMRI) recordings. The hierarchical prior
      for the current source estimation from EEG was obtained from activated brain
      areas and their intensities from an fMRI group (second-level) analysis. The fMRI
      group analysis was performed on regions of interest defined over the primary
      motor cortex, the supplementary motor area, and the somatosensory area, which are
      well-known to contribute to movement control. A sparse logistic regression method
      was applied for a nine-class classification (eight active tasks and a resting
      control task) obtaining a mean accuracy of 65.64% for time series of current
      sources, estimated from the EEG and the fMRI signals using a variational Bayesian
      method, and a mean accuracy of 22.19% for the classification of the pre-processed
      of EEG sensor signals, with a chance level of 11.11%. The higher classification
      accuracy of current sources, when compared to EEG classification accuracy, was
      attributed to the high number of sources and the different signal patterns
      obtained in the same vertex for different motor tasks. Since the inverse filter
      estimation for current sources can be done offline with the present method, the
      present method is applicable to real-time BCIs. Finally, due to the highly
      enhanced spatial distribution of current sources over the brain cortex, this
      method has the potential to identify activation patterns to design BCIs for the
      control of an affected limb in patients with stroke, or BCIs from motor imagery
      in patients with spinal cord injury.

PMID- 29358904
TI  - Inhibition of Inwardly Rectifying Potassium (Kir) 4.1 Channels Facilitates Brain
      Derived Neurotrophic Factor (BDNF) Expression in Astrocytes.
AB  - Inwardly rectifying potassium (Kir) 4.1 channels in astrocytes regulate neuronal
      excitability by mediating spatial potassium buffering. Although dysfunction of
      astrocytic Kir4.1 channels is implicated in the development of epileptic
      seizures, the functional mechanisms of Kir4.1 channels in modulating
      epileptogenesis remain unknown. We herein evaluated the effects of Kir4.1
      inhibition (blockade and knockdown) on expression of brain-derived neurotrophic
      factor (BDNF), a key modulator of epileptogenesis, in the primary cultures of
      mouse astrocytes. For blockade of Kir4.1 channels, we tested several
      antidepressant agents which reportedly bound to and blocked Kir4.1 channels in a
      subunit-specific manner. Treatment of astrocytes with fluoxetine enhanced BDNF
      mRNA expression in a concentration-dependent manner and increased the BDNF
      protein level. Other antidepressants (e.g., sertraline and imipramine) also
      increased the expression of BDNF mRNA with relative potencies similar to those
      for inhibition of Kir4.1 channels. In addition, suppression of Kir4.1 expression
      by the transfection of small interfering RNA (siRNA) targeting Kir4.1
      significantly increased the mRNA and protein levels of BDNF. The BDNF induction
      by Kir4.1 siRNA transfection was suppressed by the MEK1/2 inhibitor U0126, but
      not by the p38 MAPK inhibitor SB202190 or the JNK inhibitor SP600125. The present
      results demonstrated that inhibition of Kir4.1 channels facilitates BDNF
      expression in astrocytes primarily by activating the Ras/Raf/MEK/ERK pathway,
      which may be linked to the development of epilepsy and other neuropsychiatric
      disorders.

PMID- 29358905
TI  - A Method to Culture GABAergic Interneurons Derived from the Medial Ganglionic
      Eminence.
AB  - Understanding the mechanisms guiding interneuron development is a central aspect
      of the current research on cortical/hippocampal interneurons, which is highly
      relevant to brain function and pathology. In this methodological study we have
      addressed the setup of protocols for the reproducible culture of dissociated
      cells from murine medial ganglionic eminences (MGEs), to provide a culture system
      for the analysis of interneurons in vitro. This study includes the detailed
      protocols for the preparation of the dissociated cells, and for their culture on
      optimal substrates for cell migration or differentiation. These cultures enriched
      in interneurons may allow the investigation of the migratory behavior of
      interneuron precursors and their differentiation in vitro, up to the formation of
      morphologically identifiable GABAergic synapses. Live imaging of MGE-derived
      cells plated on proper substrates shows that they are useful to study the
      migratory behavior of the precursors, as well as the behavior of growth cones
      during the development of neurites. Most MGE-derived precursors develop into
      polarized GABAergic interneurons as determined by axonal, dendritic, and
      GABAergic markers. We present also a comparison of cells from WT and mutant mice
      as a proof of principle for the use of these cultures for the analysis of the
      migration and differentiation of GABAergic cells with different genetic
      backgrounds. The culture enriched in interneurons described here represents a
      useful experimental system to examine in a relatively easy and fast way the
      morpho-functional properties of these cells under physiological or pathological
      conditions, providing a powerful tool to complement the studies in vivo.

PMID- 29358906
TI  - Commentary: Retinal Waves Modulate an Intraretinal Circuit of Intrinsically
      Photosensitive Retinal Ganglion Cells.

PMID- 29358909
TI  - Commentary: The Predictive Processing Paradigm Has Roots in Kant.

PMID- 29358908
TI  - Delineation of Subregions in the Early Postnatal Human Cerebellum for Design
      Based Stereologic Studies.
AB  - Recent design-based stereologic studies have shown that the early postnatal (<1
      year of age) human cerebellum is characterized by very high plasticity and may
      thus be very sensitive to external and internal influences during the first year
      of life. A potential weakness of these studies is that they were not separately
      performed on functionally relevant subregions of the cerebellum, as was the case
      in a few design-based stereologic studies on the adult human cerebellum. The aim
      of the present study was to assess whether it is possible to identify
      unequivocally the primary, superior posterior, horizontal, ansoparamedian, and
      posterolateral fissures in the early postnatal human cerebellum, based on which
      functionally relevant subregions could be delineated. This was tested in 20 human
      post mortem cerebellar halves from subjects aged between 1 day and 11 months by
      means of a combined macroscopic and microscopic approach. We found that the
      superior posterior, horizontal, and posterolateral fissures can be reliably
      identified on all of the specimens. However, reliable and reproducible
      identification of the primary and ansoparamedian fissures was not possible.
      Accordingly, it appears feasible to perform subregion-specific investigations in
      the early postnatal human cerebellum when the identification of subregions is
      restricted to crus I (bordered by the superior posterior and horizontal fissures)
      and the flocculus (bordered by the posterolateral fissure). As such, it is
      recommended to define the entire cerebellar cortex as the region of interest in
      design-based stereologic studies on the early postnatal human cerebellum to
      guarantee reproducibility of results.

PMID- 29358910
TI  - An Additional Prior Retrieval Alters the Effects of a Retrieval-Extinction
      Procedure on Recent and Remote Fear Memory.
AB  - Several studies have shown that the isolated retrieval of a consolidated fear
      memory can induce a labile phase, during which extinction training can prevent
      the reinstatement, a form of relapse in which fear response to a fear-provoking
      context returns when a mild shock is presented. However, fear memory retrieval
      may also have another opposing result: the enhancement of fear memory. This
      implies that the fear memory trace can be modified by a brief retrieval. Unclear
      is whether the fear-impairing effect of retrieval-extinction (RE) is altered by a
      prior brief retrieval. The present study investigated the responses of recent and
      remote fear memories to the RE procedure after the presentation of an additional
      prior retrieval (priRet). We found that a single RE procedure effectively blocked
      the reinstatement of 2-day recent contextual fear memory. The memory-impairing
      effect of the RE procedure on recent fear was not observed when priRet was
      presented 6 or 24 h before the RE procedure. In contrast to the 2-day recent
      memory, the RE procedure failed to block the reinstatement of 36-day remote fear
      memory but successfully disrupted the return of remote fear memory after priRet.
      This memory-disruptive effect on remote memory did not occur when priRet was
      performed in a novel context. Nimodipine administration revealed that the
      blockade of priRet-induced processes recovered the effects of the RE procedure on
      both recent and remote fear memories. Our findings suggest that the
      susceptibility of recent and remote fear memories to RE procedures can be altered
      by an additional retrieval.

PMID- 29358907
TI  - Trigeminal, Visceral and Vestibular Inputs May Improve Cognitive Functions by
      Acting through the Locus Coeruleus and the Ascending Reticular Activating System:
      A New Hypothesis.
AB  - It is known that sensory signals sustain the background discharge of the
      ascending reticular activating system (ARAS) which includes the noradrenergic
      locus coeruleus (LC) neurons and controls the level of attention and alertness.
      Moreover, LC neurons influence brain metabolic activity, gene expression and
      brain inflammatory processes. As a consequence of the sensory control of ARAS/LC,
      stimulation of a sensory channel may potential influence neuronal activity and
      trophic state all over the brain, supporting cognitive functions and exerting a
      neuroprotective action. On the other hand, an imbalance of the same input on the
      two sides may lead to an asymmetric hemispheric excitability, leading to an
      impairment in cognitive functions. Among the inputs that may drive LC neurons and
      ARAS, those arising from the trigeminal region, from visceral organs and,
      possibly, from the vestibular system seem to be particularly relevant in
      regulating their activity. The trigeminal, visceral and vestibular control of
      ARAS/LC activity may explain why these input signals: (1) affect sensorimotor and
      cognitive functions which are not directly related to their specific
      informational content; and (2) are effective in relieving the symptoms of some
      brain pathologies, thus prompting peripheral activation of these input systems as
      a complementary approach for the treatment of cognitive impairments and
      neurodegenerative disorders.

PMID- 29358911
TI  - Altered Parietal Activation during Non-symbolic Number Comparison in Children
      with Prenatal Alcohol Exposure.
AB  - Number processing is a cognitive domain particularly sensitive to prenatal
      alcohol exposure, which relies on intact parietal functioning. Alcohol-related
      alterations in brain activation have been found in the parietal lobe during
      symbolic number processing. However, the effects of prenatal alcohol exposure on
      the neural correlates of non-symbolic number comparison and the numerical
      distance effect have not been investigated. Using functional magnetic resonance
      imaging (fMRI), we examined differences in brain activation associated with
      prenatal alcohol exposure in five parietal regions involved in number processing
      during a non-symbolic number comparison task with varying degrees of difficulty.
      fMRI results are presented for 27 Cape Colored children (6 fetal alcohol syndome
      (FAS)/partial FAS, 5 heavily exposed (HE) non-sydromal, 16 controls; mean age +/-
      SD = 11.7 +/- 1.1 years). Fetal alcohol exposure was assessed by interviewing
      mothers using a timeline follow-back approach. Separate subject analyses were
      performed in each of five regions of interest, bilateral horizontal intraparietal
      sulci (IPS), bilateral posterior superior parietal lobules (PSPL), and left
      angular gyrus (left AG), using the general linear model with predictors for
      number comparison and difficulty level. Mean percent signal change for each
      predictor was extracted for each subject for each region to examine group
      differences and associations with continuous measures of alcohol exposure.
      Although groups did not differ in performance, controls activated the right PSPL
      more during non-symbolic number comparison than exposed children, but this was
      not significant after controlling for maternal smoking, and the right IPS more
      than children with fetal alcohol syndrome (FAS) or partial FAS. More heavily
      exposed children recruited the left AG to a greater extent as task difficulty
      increased, possibly to compensate, in part, for impairments in function in the
      PSPL and IPS. Notably, in non-syndromal heavily exposed children activation was
      impaired in the right PSPL, but spared in the right IPS. These results extend
      previous findings of poor right IPS recruitment during symbolic number processing
      in FAS/PFAS, indicating that mental representation of relative quantity is
      affected by prenatal alcohol exposure for both symbolic and non-symbolic
      representations of quantity.

PMID- 29358912
TI  - Signal Processing in Functional Near-Infrared Spectroscopy (fNIRS):
      Methodological Differences Lead to Different Statistical Results.
AB  - Even though research in the field of functional near-infrared spectroscopy
      (fNIRS) has been performed for more than 20 years, consensus on signal processing
      methods is still lacking. A significant knowledge gap exists between established
      researchers and those entering the field. One major issue regularly observed in
      publications from researchers new to the field is the failure to consider
      possible signal contamination by hemodynamic changes unrelated to neurovascular
      coupling (i.e., scalp blood flow and systemic blood flow). This might be due to
      the fact that these researchers use the signal processing methods provided by the
      manufacturers of their measurement device without an advanced understanding of
      the performed steps. The aim of the present study was to investigate how
      different signal processing approaches (including and excluding approaches that
      partially correct for the possible signal contamination) affect the results of a
      typical functional neuroimaging study performed with fNIRS. In particular, we
      evaluated one standard signal processing method provided by a commercial company
      and compared it to three customized approaches. We thereby investigated the
      influence of the chosen method on the statistical outcome of a clinical data set
      (task-evoked motor cortex activity). No short-channels were used in the present
      study and therefore two types of multi-channel corrections based on multiple long
      channels were applied. The choice of the signal processing method had a
      considerable influence on the outcome of the study. While methods that ignored
      the contamination of the fNIRS signals by task-evoked physiological noise yielded
      several significant hemodynamic responses over the whole head, the statistical
      significance of these findings disappeared when accounting for part of the
      contamination using a multi-channel regression. We conclude that adopting signal
      processing methods that correct for physiological confounding effects might yield
      more realistic results in cases where multi-distance measurements are not
      possible. Furthermore, we recommend using manufacturers' standard signal
      processing methods only in case the user has an advanced understanding of every
      signal processing step performed.

PMID- 29358914
TI  - Bayesian Estimation of Phase Dynamics Based on Partially Sampled Spikes Generated
      by Realistic Model Neurons.
AB  - A dynamic system showing stable rhythmic activity can be represented by the
      dynamics of phase oscillators. This would provide a useful mathematical framework
      through which one can understand the system's dynamic properties. A recent study
      proposed a Bayesian approach capable of extracting the underlying phase dynamics
      directly from time-series data of a system showing rhythmic activity. Here we
      extended this method to spike data that otherwise provide only limited phase
      information. To determine how this method performs with spike data, we applied it
      to simulated spike data generated by a realistic neuronal network model. We then
      compared the estimated dynamics obtained based on the spike data with the
      dynamics theoretically derived from the model. The method successfully extracted
      the modeled phase dynamics, particularly the interaction function, when the
      amount of available data was sufficiently large. Furthermore, the method was able
      to infer synaptic connections based on the estimated interaction function. Thus,
      the method was found to be applicable to spike data and practical for
      understanding the dynamic properties of rhythmic neural systems.

PMID- 29358913
TI  - Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study.
AB  - Little is known about the neural correlates of fear learning in adolescents, a
      population at increased risk for anxiety disorders. Healthy adolescents (mean age
      16.26) and adults (mean age 29.85) completed a fear learning paradigm across two
      stages during functional magnetic resonance imaging (fMRI). Stage 1 involved
      conditioning and extinction, and stage 2 involved extinction recall, re
      conditioning, followed by re-extinction. During extinction recall, we observed a
      higher skin conductance response to the CS+ relative to CS- in adolescents
      compared to adults, which was accompanied by a reduction in dorsolateral
      prefrontal cortex (dlPFC) activity. Relative to adults, adolescents also had
      significantly reduced activation in the ventromedial PFC, dlPFC, posterior
      cingulate cortex (PCC), and temporoparietal junction (TPJ) during extinction
      recall compared to late extinction. Age differences in PCC activation between
      late extinction and late conditioning were also observed. These results show for
      the first time that healthy adolescent humans show different behavioral
      responses, and dampened PFC activity during short-term extinction recall compared
      to healthy adults. We also identify the PCC and TPJ as novel regions that may be
      associated with impaired extinction in adolescents. Also, while adults showed
      significant correlations between differential SCR and BOLD activity in some brain
      regions during late extinction and recall, adolescents did not show any
      significant correlations. This study highlights adolescent-specific neural
      correlates of extinction, which may explain the peak in prevalence of anxiety
      disorders during adolescence.

PMID- 29358915
TI  - Application of a Simplified Method for Estimating Perfusion Derived from
      Diffusion-Weighted MR Imaging in Glioma Grading.
AB  - Purpose: To evaluate the feasibility of a simplified method based on diffusion
      weighted imaging (DWI) acquired with three b-values to measure tissue perfusion
      linked to microcirculation, to validate it against from perfusion-related
      parameters derived from intravoxel incoherent motion (IVIM) and dynamic contrast
      enhanced (DCE) magnetic resonance (MR) imaging, and to investigate its utility to
      differentiate low- from high-grade gliomas. Materials and Methods: The
      prospective study was approved by the local institutional review board and
      written informed consent was obtained from all patients. From May 2016 and May
      2017, 50 patients confirmed with glioma were assessed with multi-b-value DWI and
      DCE MR imaging at 3.0 T. Besides conventional apparent diffusion coefficient
      (ADC0,1000) map, perfusion-related parametric maps for IVIM-derived perfusion
      fraction (f) and pseudodiffusion coefficient (D*), DCE MR imaging-derived
      pharmacokinetic metrics, including Ktrans, ve and vp, as well as a metric named
      simplified perfusion fraction (SPF), were generated. Correlation between
      perfusion-related parameters was analyzed by using the Spearman rank correlation.
      All imaging parameters were compared between the low-grade (n = 19) and high
      grade (n = 31) groups by using the Mann-Whitney U test. The diagnostic
      performance for tumor grading was evaluated with receiver operating
      characteristic (ROC) analysis. Results: SPF showed strong correlation with IVIM
      derived f and D* (rho = 0.732 and 0.716, respectively; both P < 0.001). Compared
      with f, SPF was more correlated with DCE MR imaging-derived Ktrans (rho = 0.607;
      P < 0.001) and vp (rho = 0.397; P = 0.004). Among all parameters, SPF achieved
      the highest accuracy for differentiating low- from high-grade gliomas, with an
      area under the ROC curve value of 0.942, which was significantly higher than that
      of ADC0,1000 (P = 0.004). By using SPF as a discriminative index, the diagnostic
      sensitivity and specificity were 87.1% and 94.7%, respectively, at the optimal
      cut-off value of 19.26%. Conclusion: The simplified method to measure tissue
      perfusion based on DWI by using three b-values may be helpful to differentiate
      low- from high-grade gliomas. SPF may serve as a valuable alternative to measure
      tumor perfusion in gliomas in a noninvasive, convenient and efficient way.

PMID- 29358916
TI  - Reducing the Levels of Akt Activation by PDK1 Knock-in Mutation Protects Neuronal
      Cultures against Synthetic Amyloid-Beta Peptides.
AB  - The Akt kinase has been widely assumed for years as a key downstream effector of
      the PI3K signaling pathway in promoting neuronal survival. This notion was
      however challenged by the finding that neuronal survival responses were still
      preserved in mice with reduced Akt activity. Moreover, here we show that the Akt
      signaling is elevated in the aged brain of two different mice models of Alzheimer
      Disease. We manipulate the rate of Akt stimulation by employing knock-in mice
      expressing a mutant form of PDK1 (phosphoinositide-dependent protein kinase 1)
      with reduced, but not abolished, ability to activate Akt. We found increased
      membrane localization and activity of the TACE/ADAM17 alpha-secretase in the
      brain of the PDK1 mutant mice with concomitant TNFR1 processing, which provided
      neurons with resistance against TNFalpha-induced neurotoxicity. Opposite to the
      Alzheimer Disease transgenic mice, the PDK1 knock-in mice exhibited an age
      dependent attenuation of the unfolding protein response, which protected the
      mutant neurons against endoplasmic reticulum stressors. Moreover, these two
      mechanisms cooperatively provide the mutant neurons with resistance against
      amyloid-beta oligomers, and might singularly also contribute to protect these
      mice against amyloid-beta pathology.

PMID- 29358917
TI  - Association of Peripheral Interleukin-6 with Global Cognitive Decline in Non
      demented Adults: A Meta-Analysis of Prospective Studies.
AB  - Background: Elevated biomarkers of systemic inflammation have been reported in
      individuals with cognitive decline, however, most of the literature concerns
      cross-sectional analyses that have produced mixed results. This study
      investigates the etiology of this association by performing meta-analyses on
      prospective studies investigating the relationship between baseline interleukin-6
      (IL-6), an established marker of peripheral inflammation, with cognitive decline
      risk in non-demented adults at follow-up. Methods: We reviewed studies reporting
      peripheral IL-6 with future cognitive decline, up to February 2017 by searching
      the PubMed, Science Direct, Scopus and Google Scholar databases. Studies which
      contained odds ratios (ORs) for the association between circulating baseline IL-6
      and longitudinal cognitive performance in non-demented community dwelling older
      adults were pooled in random-effects models. Results: The literature search
      retrieved 5,642 potential articles, of which 7 articles containing 8 independent
      aging cohorts were eligible for review. Collectively, these studies included
      15,828 participants at baseline. Those with high circulating IL-6 were 1.42 times
      more likely to experience global cognitive decline at follow-up, over a 2-7-year
      period, compared to those with low IL-6 (OR 1.42, 95% CI 1.18-1.70; p < 0.001).
      Subgroup and sensitivity analyses suggests that this association is independent
      of the study sample size, duration of follow-up and cognitive assessments used.
      Conclusions: These results add further evidence for the association between high
      peripheral inflammation, as measured by blood IL-6, and global cognitive decline.
      Measuring circulating IL-6 may be a useful indication for future cognitive
      health.

PMID- 29358918
TI  - Longitudinal Analysis of Fecal Microbiome and Pathologic Processes in a Rotenone
      Induced Mice Model of Parkinson's Disease.
AB  - Recent studies reported an association between gut microbiota composition and
      Parkinson's disease (PD). However, we know little about the relationship between
      microbiome dysbiosis and the pathogenesis of PD. The objective of this study was
      to describe the evolution of fecal microbiota using an oral rotenone model of PD
      from a longitudinal study over a period of 4 weeks. Gastrointestinal function was
      assessed by measuring fecal pellet output, motor functions was assessed by open
      field and pole tests every week. alpha-synuclein pathology, inflammation and
      tyrosine hydroxylase (TH) neuron loss from the middle brain were also analyzed.
      Fecal samples were collected every week followed by 16S rRNA sequencing and
      bioinformatics analysis. We reported that chronically oral administered rotenone
      caused gastrointestinal dysfunction and microbiome dysbiosis prior to motor
      dysfunction and central nervous system (CNS) pathology. 16S rRNA sequencing of
      fecal microbiome showed rotenone-treated mice exhibited fecal microbiota
      dysbiosis characterized by an overall decrease in bacterial diversity and a
      significant change of microbiota composition, notably members of the phyla
      Firmicutes and Bacteroidetes, with an increase in Firmicutes/Bacteroidetes ratio
      after 3 weeks of rotenone treatment. Moreover, rotenone-induced gastrointestinal
      and motor dysfunctions were observed to be robustly correlated with changes in
      the composition of fecal microbiota. Our results demonstrated that gut microbiome
      perturbation might contribute to rotenone toxicity in the initiation of PD and
      brought a new insight in the pathogenesis of PD. Novel therapeutic options aimed
      at modifying the gut microbiota composition might postpone the onset and
      following cascade of neurodegeneration.

PMID- 29358919
TI  - The Calcium-Induced Regulation in the Molecular and Transcriptional Circuitry of
      Human Inflammatory Response and Autoimmunity.
AB  - Rheumatoid arthritis synovial fibroblasts (RASFs) are fundamental effector cells
      in RA driving the joint inflammation and deformities. Celastrol is a natural
      compound that exhibits a potent anti-arthritic effect promoting endoplasmic
      reticulum (ER) stress mediated by intracellular calcium (Ca2+) mobilization. Ca2+
      is a second messenger regulating a variety of cellular processes. We hypothesized
      that the compound, celastrol, affecting cytosolic Ca2+ mobilization could serve
      as a novel strategy to combat RA. To address this issue, celastrol was used as a
      molecular tool to assay the inflammatory gene expression profile regulated by
      Ca2+. We confirmed that celastrol treatment mobilized cytosolic Ca2+ in patient
      derived RASFs. It was found that 23 genes out of 370 were manipulated by Ca2+
      mobilization using an inflammatory and autoimmunity PCR array following
      independent quantitative PCR validation. Most of the identified genes were
      downregulated and categorized into five groups corresponding to their cellular
      responses participating in RA pathogenesis. Accordingly, a signaling network map
      demonstrating the possible molecular circuitry connecting the functions of the
      products of these genes was generated based on literature review. In addition, a
      bioinformatics analysis revealed that celastrol-induced Ca2+ mobilization gene
      expression profile showed a novel mode of action compared with three FDA-approved
      rheumatic drugs (methotrexate, rituximab and tocilizumab). To the best of our
      knowledge, this is a pioneer work charting the Ca2+ signaling network on the
      regulation of RA-associated inflammatory gene expression.

PMID- 29358920
TI  - beta-Sheet Breaker Peptide-HPYD for the Treatment of Alzheimer's Disease: Primary
      Studies on Behavioral Test and Transcriptional Profiling.
AB  - Background: Alzheimer's disease (AD), is a progressive neurodegenerative disease
      that is characterized by cognitive loss. Most researchers believe that
      aggregation and accumulation of beta-amyloid peptides (Abeta) in brain cells are
      the central pathological hallmark of this disease. Methods: Based on the amyloid
      hypothesis, a 10 amino acids beta-sheet breaker peptide HPYD (His-Lys-Gln-Leu-Pro
      Phe-Tyr-Glu-Glu-Asp) was designed according to the structure and sequence of the
      previous designed peptide H102. Accelerated stability test, thioflavine T (ThT)
      fluorescence spectral analysis and transmission electron microscopy (TEM) imaging
      were performed to detect the stability and inhibitory effects on the aggregation
      of Abeta1-42 by H102 and HPYD. FITC-labeled HPYD was first tested to determine
      whether it could be transferred along the olfactory pathway to the brain after
      nasal administration to mice. Subsequently, the Morris Water Maze (MWM) test for
      behavioral analysis was used to investigate the learning and memory ability of
      APP/PS1 transgenic mice by HPYD. Immunohistochemistry and western blot analysis
      was performed to determine the role of HPYD on Abeta and APP protein levels. In
      addition, microarray analysis was used to evaluate the effect of HPYD on gene
      expression in AD mouse models. Results: Our in vitro results demonstrated that
      HPYD had enhanced stability and inhibitory effects on Abeta1-42 aggregation
      compared to H102. HPYD could be delivered into the brain through nasal
      administration and improved the learning and memory ability in APP/PS1 transgenic
      mouse models by reducing Abeta and APP protein levels. In addition, microarray
      analyses suggested that several genes related to the inflammatory pathway, AD and
      gluco-lipid metabolism were dysregulated and could be restored to almost normal
      levels after HPYD administration to mice. Conclusions: Our results demonstrated
      that HPYD could be a potential therapeutic drug candidate for the treatment of
      AD.

PMID- 29358921
TI  - 2-Iminobiotin Superimposed on Hypothermia Protects Human Neuronal Cells from
      Hypoxia-Induced Cell Damage: An in Vitro Study.
AB  - Perinatal asphyxia represents one of the major causes of neonatal morbidity and
      mortality. Hypothermia is currently the only established treatment for hypoxic
      ischemic encephalopathy (HIE), but additional pharmacological strategies are
      being explored to further reduce the damage after perinatal asphyxia. The aim of
      this study was to evaluate whether 2-iminobiotin (2-IB) superimposed on
      hypothermia has the potential to attenuate hypoxia-induced injury of neuronal
      cells. In vitro hypoxia was induced for 7 h in neuronal IMR-32 cell cultures.
      Afterwards, all cultures were subjected to 25 h of hypothermia (33.5 degrees C),
      and incubated with vehicle or 2-IB (10, 30, 50, 100, and 300 ng/ml). Cell
      morphology was evaluated by brightfield microscopy. Cell damage was analyzed by
      LDH assays. Production of reactive oxygen species (ROS) was measured using
      fluorometric assays. Western blotting for PARP, Caspase-3, and the phosphorylated
      forms of akt and erk1/2 was conducted. To evaluate early apoptotic events and
      signaling, cell protein was isolated 4 h post-hypoxia and human apoptosis
      proteome profiler arrays were performed. Twenty-five hour after the hypoxic
      insult, clear morphological signs of cell damage were visible and significant LDH
      release as well as ROS production were observed even under hypothermic
      conditions. Post-hypoxic application of 2-IB (10 and 30 ng/ml) reduced the
      hypoxia-induced LDH release but not ROS production. Phosphorylation of erk1/2 was
      significantly increased after hypoxia, while phosphorylation of akt, protein
      expression of Caspase-3 and cleavage of PARP were only slightly increased.
      Addition of 2-IB did not affect any of the investigated proteins. Apoptosis
      proteome profiler arrays performed with cellular protein obtained 4 h after
      hypoxia revealed that post-hypoxic application of 2-IB resulted in a >= 25% down
      regulation of 10/35 apoptosis-related proteins: Bad, Bax, Bcl-2, cleaved Caspase
      3, TRAILR1, TRAILR2, PON2, p21, p27, and phospho Rad17. In summary, addition of 2
      IB during hypothermia is able to attenuate hypoxia-induced neuronal cell damage
      in vitro. Combination treatment of hypothermia with 2-IB could be a promising
      strategy to reduce hypoxia-induced neuronal cell damage and should be considered
      in further animal and clinical studies.

PMID- 29358922
TI  - Commentary: Human Pathophysiological Adaptations to the Space Environment.

PMID- 29358924
TI  - Temporal Courses in EEG Theta and Alpha Activity in the Dynamic Health Qigong
      Techniques Wu Qin Xi and Liu Zi Jue.
AB  - Health Qigong is a common technique of Traditional Chinese Medicine applied to
      strengthen mental and physical health. Several studies report increases in EEG
      theta and alpha activity after meditative Qigong techniques indicating a relaxed
      state of mind. To date, little is known on the effects of dynamic Health Qigong
      techniques that comprise bodily movements on brain activity. In the current
      study, we compared effects of two dynamic Health Qigong techniques on EEG brain
      activity. Subjects performed the techniques Wu Qin Xi (five animals play) and Liu
      Zi Jue (six healing sounds) in a within-subjects design. Eyes-open and eyes
      closed resting EEG was recorded before and immediately after each 15-min practice
      block. Additionally, the Profile of Mood States (POMS) questionnaire was
      administered at pretest, and after each 15-min practice block. Results show a
      decrease in alpha activity after 15 min, followed by an increase after 30 min in
      the Health Qigong technique Liu Zi Jue. Theta activity was decreased after 15
      min, followed by an increase after 30 min in the technique Wu Qin Xi. Results of
      the POMS indicated an increased vigor-activity level with decreased fatigue and
      tension-anxiety levels in both techniques after 30 min of practice. Our results
      demonstrate different temporal dynamics in EEG theta and alpha activity for the
      Health Qigong techniques Wu Qin Xi and Liu Zi Jue. We hypothesize that the found
      brain activation patterns result from different attentional focusing styles and
      breathing techniques performed during the investigated Health Qigong techniques.

PMID- 29358923
TI  - Commensal Homeostasis of Gut Microbiota-Host for the Impact of Obesity.
AB  - Gut microbiota and their metabolites have been linked to a series of chronic
      diseases such as obesity and other metabolic dysfunctions. Obesity is an
      increasingly serious international health issue that may lead to a risk of
      insulin resistance and other metabolic diseases. The relationship between gut
      microbiota and the host is both interdependent and relatively independent. In
      this review, the causality of gut microbiota and its role in the pathogenesis and
      intervention of obesity is comprehensively presented to include human genotype,
      enterotypes, interactions of gut microbiota with the host, microbial metabolites,
      and energy homeostasis all of which may be influenced by dietary nutrition. Diet
      can enhance, inhibit, or even change the composition and functions of the gut
      microbiota. The metabolites they produce depend upon the dietary substrates
      provided, some of which have indispensable functions for the host. Therefore,
      diet is a key factor that maintains or not a healthy commensal relationship. In
      addition, the specific genotype of the host may impact the phylogenetic
      compositions of gut microbiota through the production of host metabolites. The
      commensal homeostasis of gut microbiota is favored by a balance of microbial
      composition, metabolites, and energy. Ultimately the desired commensal
      relationship is one of mutual support. This article analyzes the clues that
      result in patterns of commensal homeostasis. A deeper understanding of these
      interactions is beneficial for developing effective prevention, diagnosis, and
      personalized therapeutic strategies to combat obesity and other metabolic
      diseases. The idea we discuss is meant to improve human health by shaping or
      modulating the beneficial gut microbiota.

PMID- 29358925
TI  - To Message or Browse? Exploring the Impact of Phone Use Patterns on Male
      Adolescents' Consumption of Palatable Snacks.
AB  - Surveys of mobile phone usage suggest that adolescents habitually use their
      phones while eating. In this study, we explored whether the manner in which one
      uses a mobile phone - to engage in a social or non-social activity - can affect
      appetite regulation. Participants were fifty male adolescents randomly assigned
      to engage in one of the following phone-based activities: (1) sending and
      receiving messages (social activity), or (2) reading a neutral article (non
      social activity). When given the opportunity to snack, participants in the
      messaging group consumed more snacks that those who read the article. Our
      findings correspond to a large literature emphasizing social influences on food
      intake, and suggest that phone use patterns may predispose an individual to
      overeating.

PMID- 29358926
TI  - Sad Facial Expressions Increase Choice Blindness.
AB  - Previous studies have discovered a fascinating phenomenon known as choice
      blindness-individuals fail to detect mismatches between the face they choose and
      the face replaced by the experimenter. Although previous studies have reported a
      couple of factors that can modulate the magnitude of choice blindness, the
      potential effect of facial expression on choice blindness has not yet been
      explored. Using faces with sad and neutral expressions (Experiment 1) and faces
      with happy and neutral expressions (Experiment 2) in the classic choice blindness
      paradigm, the present study investigated the effects of facial expressions on
      choice blindness. The results showed that the detection rate was significantly
      lower on sad faces than neutral faces, whereas no significant difference was
      observed between happy faces and neutral faces. The exploratory analysis of
      verbal reports found that participants who reported less facial features for sad
      (as compared to neutral) expressions also tended to show a lower detection rate
      of sad (as compared to neutral) faces. These findings indicated that sad facial
      expressions increased choice blindness, which might have resulted from inhibition
      of further processing of the detailed facial features by the less attractive sad
      expressions (as compared to neutral expressions).

PMID- 29358927
TI  - Improved Digit Span in Children after a 6-Week Intervention of Playing a Musical
      Instrument: An Exploratory Randomized Controlled Trial.
AB  - Previous studies have reported that music training not only improves children's
      musical skills, but also enhances their cognitive functions. However, there is a
      disagreement about what domain(s) might be affected. Moreover, effects of short
      term (<several months) instrumental training have not been examined, although
      more basic studies have suggested neuroplasticity within several weeks.
      Consequently, the present exploratory pilot study investigated the effect of a
      six-week instrumental practice program (i.e., playing the keyboard harmonica) on
      children's cognitive functions using a randomized controlled trial. Forty
      children (aged 6-8 years) were randomly assigned to either the experimental group
      (n = 20), which received a 6-week (12-session) keyboard harmonica curriculum, or
      an untrained control group (n = 20). Different from traditional instrumental
      training, the curriculum did not use musical scores to emphasize creating
      association between sound (auditory modality) and finger movement (somato-motor
      system). Cognitive measurements included verbal ability, processing speed,
      working memory, and inhibitory control, which were administered before and after
      the curriculum in both groups. After the 6-week training, only the experimental
      group showed a significant improvement in the Digit Span test (especially in the
      Digit Span Backward) that measures working memory. However, no significant
      influences were found on the other cognitive tests. The result suggests that
      several weeks of instrumental music training may be beneficial to improving
      children's working memory. In addition, we used an inexpensive and portable
      keyboard harmonica; therefore, our instructional method is easy to apply in
      classrooms or other circumstances. If the method is applied to music lessons in
      schools or in the community, it may help improve children's working memory.

PMID- 29358928
TI  - Commentary: Sure I'm Sure: Prefrontal Oscillations Support Metacognitive
      Monitoring of Decision Making.

PMID- 29358929
TI  - Organotins in Neuronal Damage, Brain Function, and Behavior: A Short Review.
AB  - The consequences of exposure to environmental contaminants have shown significant
      effects on brain function and behavior in different experimental models. The
      endocrine-disrupting chemicals (EDC) present various classes of pollutants with
      potential neurotoxic actions, such as organotins (OTs). OTs have received special
      attention due to their toxic effects on the central nervous system, leading to
      abnormal mammalian neuroendocrine axis function. OTs are organometallic
      pollutants with a tin atom bound to one or more carbon atoms. OT exposure may
      occur through the food chain and/or contaminated water, since they have multiple
      applications in industry and agriculture. In addition, OTs have been used with
      few legal restrictions in the last decades, despite being highly toxic. In
      addition to their action as EDC, OTs can also cross the blood-brain barrier and
      show relevant neurotoxic effects, as observed in several animal model studies
      specifically involving the development of neurodegenerative processes,
      neuroinflammation, and oxidative stress. Thus, the aim of this short review is to
      summarize the toxic effects of the most common OT compounds, such as
      trimethyltin, tributyltin, triethyltin, and triphenyltin, on the brain with a
      focus on neuronal damage as a result of oxidative stress and neuroinflammation.
      We also aim to present evidence for the disruption of behavioral functions,
      neurotransmitters, and neuroendocrine pathways caused by OTs.

PMID- 29358930
TI  - Phylogeny of Vibrio vulnificus from the Analysis of the Core-Genome: Implications
      for Intra-Species Taxonomy.
AB  - Vibrio vulnificus (Vv) is a multi-host pathogenic species currently subdivided
      into three biotypes (Bts). The three Bts are human-pathogens, but only Bt2 is
      also a fish-pathogen, an ability that is conferred by a transferable virulence
      plasmid (pVvbt2). Here we present a phylogenomic analysis from the core genome of
      80 Vv strains belonging to the three Bts recovered from a wide range of
      geographical and ecological sources. We have identified five well-supported
      phylogenetic groups or lineages (L). L1 comprises a mixture of clinical and
      environmental Bt1 strains, most of them involved in human clinical cases related
      to raw seafood ingestion. L2 is formed by a mixture of Bt1 and Bt2 strains from
      various sources, including diseased fish, and is related to the aquaculture
      industry. L3 is also linked to the aquaculture industry and includes Bt3 strains
      exclusively, mostly related to wound infections or secondary septicemia after
      farmed-fish handling. Lastly, L4 and L5 include a few strains of Bt1 associated
      with specific geographical areas. The phylogenetic trees for ChrI and II are not
      congruent to one another, which suggests that inter- and/or intra-chromosomal
      rearrangements have been produced along Vv evolution. Further, the phylogenetic
      trees for each chromosome and the virulence plasmid were also not congruent,
      which also suggests that pVvbt2 has been acquired independently by different
      clones, probably in fish farms. From all these clones, the one with zoonotic
      capabilities (Bt2-Serovar E) has successfully spread worldwide. Based on these
      results, we propose a new updated classification of the species based on
      phylogenetic lineages rather than on Bts, as well as the inclusion of all Bt2
      strains in a pathovar with the particular ability to cause fish vibriosis, for
      which we suggest the name "piscis."

PMID- 29358931
TI  - The Transcription Factor T-Bet Is Regulated by MicroRNA-155 in Murine Anti-Viral
      CD8+ T Cells via SHIP-1.
AB  - We report here that the expression of the transcription factor T-bet, which is
      known to be required for effector cytotoxic CD8+ T lymphocytes (CTL) generation
      and effector memory cell formation, is regulated in CTL by microRNA-155 (miR
      155). Importantly, we show that the proliferative effect of miR-155 on CD8+ T
      cells is mediated by T-bet. T-bet levels in CTL were controlled in vivo by miR
      155 via SH2 (Src homology 2)-containing inositol phosphatase-1 (SHIP-1), a known
      direct target of miR-155, and SHIP-1 directly downregulated T-bet. Our studies
      reveal an important and unexpected signaling axis between miR-155, T-bet, and
      SHIP-1 in in vivo CTL responses and suggest an important signaling module that
      regulates effector CTL immunity.

PMID- 29358932
TI  - PSORI-CM02 Formula Increases CD4+ Foxp3+ Regulatory T Cell Frequency and
      Ameliorates Imiquimod-Induced Psoriasis in Mice.
AB  - Psoriasis is an autoimmune and inflammatory disease, which is estimated to affect
      2-3% of the population in the world. PSORI-CM02 is an empirical formula of
      Chinese medicine optimized from Yin Xie Ling, which is widely used to treat
      psoriasis in China for decades. However, its antipsoriatic mechanisms are still
      not well understood. Here, we explored the therapeutic effects of PSORI-CM02 on
      psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse
      models and human HaCaT cells. In experiments in vitro, PSORI-CM02 significantly
      inhibited HaCaT cell proliferation in dose-dependent and time-dependent manners.
      Furthermore, it hindered the progression of HaCaT cell cycle and arrested HaCaT
      cells at G1 phase. On the other hand, our in vivo studies demonstrated that PSORI
      CM02 dramatically reduced psoriasis area and severity index scores and lesion
      temperature in imiquimod-induced psoriatic mice. The antioxidative activities of
      glutathione, catalase, and superoxide dismutase were increased while oxidative
      activity of malonaldehyde was markedly decreased after treatments with PSORI
      CM02. PSORI-CM02 also suppressed the mRNA expression of proinflammatory
      cytokines, including TNF-alpha, IL-6, and IL-17, and lowered their protein levels
      in the serum as well. In addition, PSORI-CM02 could reduce the expression of
      IKKalpha and NF-kappaB in psoriatic skin tissue. It also upregulated the
      proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and
      spleens and promoted CD4+ CD25+ Treg proliferation in vitro. Taken together, our
      research demonstrated that PSORI-CM02 inhibited HaCaT cell proliferation by
      arresting them at G1 phase and alleviated systemic inflammation and psoriasis in
      mice via altering the oxidative/anti-oxidative status, tipping the balance
      between Th17 responsiveness and CD4+ Foxp3+ Treg generation, and suppressing the
      expression of proinflammatory cytokines as well as NF-kappaB signaling.

PMID- 29358933
TI  - Age and Influenza-Specific Pre-Vaccination Antibodies Strongly Affect Influenza
      Vaccine Responses in the Icelandic Population whereas Disease and Medication Have
      Small Effects.
AB  - Influenza vaccination remains the best strategy for the prevention of influenza
      virus-related disease and reduction of disease severity and mortality. However,
      there is large individual variation in influenza vaccine responses. In this
      study, we investigated the effects of gender, age, underlying diseases, and
      medication on vaccine responses in 1,852 Icelanders of broad age range who
      received trivalent inactivated influenza virus vaccination in 2012, 2013, or
      2015. Hemagglutination inhibition (HAI) and microneutralization (MN) titers were
      measured in pre- and post-vaccination sera. Of the variables tested, the
      strongest association was with level of pre-vaccination titer that explained a
      major part of the variance observed in post-vaccination titers, ranging from 19
      to 29%, and from 7 to 21% in fold change (FC), depending on the strain and
      serological (HAI or MN) analysis performed. Thus, increasing pre-vaccination
      titer associated with decreasing FC (P = 1.1 * 10-99-8.6 * 10-30) and increasing
      post-vaccination titer (P = 2.1 * 10-159-1.1 * 10-123). Questionnaires completed
      by 87% of the participants revealed that post-vaccination HAI titer showed
      association with repeated previous influenza vaccinations. Gender had no effect
      on vaccine response whereas age had a strong effect and explained 1.6-3.1% of HAI
      post-vaccination titer variance and 3.1% of H1N1 MN titer variance. Vaccine
      response, both fold increase and seroprotection rate (percentage of individuals
      reaching HAI >= 40 or MN >= 20), was higher in vaccinees <=37 years of age (YoA)
      than all other age groups. Furthermore, a reduction was observed in the H1N1 MN
      titer in people >=63 YoA, demonstrating a decreased neutralizing functionality of
      vaccine-induced antibodies at older age. We tested the effects of underlying
      autoimmune diseases, asthma and allergic diseases and did not observe significant
      associations with vaccine responses. Intake of immune modulating medication did
      not show any association. Taken together, our results show that previous
      encounter of influenza vaccination or infection, reflected in high HAI and MN pre
      vaccination titer has the strongest negative effect on vaccine responses measured
      as FC and the strongest positive effect on post-vaccination titer. Increasing age
      had also an effect but not gender, underlying disease or medication.

PMID- 29358934
TI  - Regulatory T Cell Metabolism in the Hepatic Microenvironment.
AB  - Thymic-derived naturally occurring regulatory T cells (tTreg) are crucial for
      maintaining peripheral immune homeostasis. They play a crucial role in preventing
      autoimmunity and maintaining organ transplant without requiring
      immunosuppression. Cellular metabolism has recently emerged as an important
      regulator of adaptive immune cell balance between Treg and effector T cells.
      While the metabolic requirements of conventional T cells are increasingly
      understood, the role of Treg cellular metabolism is less clear. The continuous
      exposure of metabolites and nutrients to the human liver via the portal blood
      flow influences the lineage fitness, function, proliferation, migration, and
      survival of Treg cells. As cellular metabolism has an impact on its function, it
      is crucial to understand the metabolic pathways wiring in regulatory T cells.
      Currently, there are ongoing early phase clinical trials with polyclonal and
      antigen-specific good manufacturing practice (GMP) Treg therapy to treat
      autoimmune diseases and organ transplantation. Thus, enhancing immunometabolic
      pathways of Treg by translational approach with existing or new drugs would
      utilize Treg cells to their full potential for effective cellular therapy.

PMID- 29358935
TI  - Infection of Human Monocytes with Leishmania infantum Strains Induces a
      Downmodulated Response when Compared with Infection with Leishmania braziliensis.
AB  - Human infection with different species of Leishmania leads to distinct clinical
      manifestations, ranging from relatively mild cutaneous (Leishmania braziliensis)
      to severe visceral (Leishmania infantum) forms of leishmaniasis. Here, we asked
      whether in vitro infection of human monocytes by Leishmania strains responsible
      for distinct clinical manifestations leads to early changes in immunological
      characteristics and ability of the host cells to control Leishmania. We evaluated
      the expression of toll-like receptors and MHC class II molecules, cytokines, and
      Leishmania control by human monocytes following short-term infection with L.
      braziliensis (M2904), a reference strain of L. infantum (BH46), and a wild strain
      of L. infantum (wild). The induction of TLR2, TLR9, and HLA-DR were all lower in
      L. infantum when compared with L. braziliensis-infected cells. Moreover, L.
      infantum-infected monocytes (both strains) produced lower TNF-alpha and a lower
      TNF-alpha/IL-10 ratio, resulting in a weaker inflammatory profile and a 100-fold
      less effective control of Leishmania than cells infected with L. braziliensis.
      Our results show that L. infantum strains fail to induce a strong inflammatory
      response, less activation, and less control of Leishmania from human monocytes,
      when compared with that induced by L. braziliensis infection. This functional
      profile may help explain the distinct clinical course observed in patients
      infected with the different Leishmania species.

PMID- 29358936
TI  - Epstein-Barr Virus and Hemophagocytic Lymphohistiocytosis.
AB  - Epstein-Barr virus (EBV) is a ubiquitous virus that infects nearly all people
      worldwide without serious sequela. However, for patients who have genetic
      diseases which predispose them to the development of hemophagocytic
      lymphohistiocytosis (HLH), EBV infection is a life-threatening problem. As a part
      of a themed collection of articles on EBV infection and human primary immune
      deficiencies, we will review key concepts related to the understanding and
      treatment of HLH.

PMID- 29358937
TI  - Feeding Immunity: Physiological and Behavioral Responses to Infection and
      Resource Limitation.
AB  - Resources are a core currency of species interactions and ecology in general
      (e.g., think of food webs or competition). Within parasite-infected hosts,
      resources are divided among the competing demands of host immunity and growth as
      well as parasite reproduction and growth. Effects of resources on immune
      responses are increasingly understood at the cellular level (e.g., metabolic
      predictors of effector function), but there has been limited consideration of how
      these effects scale up to affect individual energetic regimes (e.g., allocation
      trade-offs), susceptibility to infection, and feeding behavior (e.g., responses
      to local resource quality and quantity). We experimentally rewilded laboratory
      mice (strain C57BL/6) in semi-natural enclosures to investigate the effects of
      dietary protein and gastrointestinal nematode (Trichuris muris) infection on
      individual-level immunity, activity, and behavior. The scale and realism of this
      field experiment, as well as the multiple physiological assays developed for
      laboratory mice, enabled us to detect costs, trade-offs, and potential
      compensatory mechanisms that mice employ to battle infection under different
      resource conditions. We found that mice on a low-protein diet spent more time
      feeding, which led to higher body fat stores (i.e., concentration of a satiety
      hormone, leptin) and altered metabolite profiles, but which did not fully
      compensate for the effects of poor nutrition on albumin or immune defenses.
      Specifically, immune defenses measured as interleukin 13 (IL13) (a primary
      cytokine coordinating defense against T. muris) and as T. muris-specific IgG1
      titers were lower in mice on the low-protein diet. However, these reduced
      defenses did not result in higher worm counts in mice with poorer diets. The lab
      mice, living outside for the first time in thousands of generations, also
      consumed at least 26 wild plant species occurring in the enclosures, and DNA
      metabarcoding revealed that the consumption of different wild foods may be
      associated with differences in leptin concentrations. When individual foraging
      behavior was accounted for, worm infection significantly reduced rates of host
      weight gain. Housing laboratory mice in outdoor enclosures provided new insights
      into the resource costs of immune defense to helminth infection and how hosts
      modify their behavior to compensate for those costs.

PMID- 29358939
TI  - Seasonal Influenza Split Vaccines Confer Partial Cross-Protection against
      Heterologous Influenza Virus in Ferrets When Combined with the CAF01 Adjuvant.
AB  - Influenza epidemics occur annually, and estimated 5-10% of the adult population
      and 20-30% of children will become ill from influenza infection. Seasonal
      vaccines primarily work through the induction of neutralizing antibodies against
      the principal surface antigen hemagglutinin (HA). This important role of HA
      specific antibodies explains why previous pandemics have emerged when new HAs
      have appeared in circulating human viruses. It has long been recognized that
      influenza virus-specific CD4(+) T cells are important in protection from
      infection through direct effector mechanisms or by providing help to B cells and
      CD8(+) T cells. However, the seasonal influenza vaccine is poor at inducing
      CD4(+) T-cell responses and needs to be combined with an adjuvant facilitating
      this response. In this study, we applied the ferret model to investigate the
      cross-protective efficacy of a heterologous trivalent influenza split-virion
      (TIV) vaccine adjuvanted with the CAF01 adjuvant, with proven ability to induce
      CD4(+) T-cell and antibody responses in mice, ferrets, pigs, primates, and
      humans. Our results indicate that CAF01-adjuvanted vaccine induces HA inhibition
      (HAI)-independent protection after heterologous challenge, manifested as reduced
      viral load and fever. On the other hand, we observe increased inflammation in the
      airways and more neutrophil and mononuclear cell infiltration in these ferrets
      when compared with optimally protected animals, i.e., ferrets receiving the same
      vaccine but a homologous challenge. This suggest that HAI-independent immunity
      induced by TIV + CAF01 can reduce viral shedding and systemic disease symptoms,
      but does not reduce local inflammation in the nasal cavity.

PMID- 29358938
TI  - Acute Pharmacologic Degradation of a Stable Antigen Enhances Its Direct
      Presentation on MHC Class I Molecules.
AB  - Bifunctional degraders, also referred to as proteolysis-targeting chimeras
      (PROTACs), are a recently developed class of small molecules. They were designed
      to specifically target endogenous proteins for ubiquitin/proteasome-dependent
      degradation and to thereby interfere with pathological mechanisms of diseases,
      including cancer. In this study, we hypothesized that this process of acute
      pharmacologic protein degradation might increase the direct MHC class I
      presentation of degraded targets. By studying this question, we contribute to an
      ongoing discussion about the origin of peptides feeding the MHC class I
      presentation pathway. Two scenarios have been postulated: peptides can either be
      derived from homeostatic turnover of mature proteins and/or from short-lived
      defective ribosomal products (DRiPs), but currently, it is still unclear to what
      ratio and efficiency both pathways contribute to the overall MHC class I
      presentation. We therefore generated the intrinsically stable model antigen GFP
      S8L-F12 that was susceptible to acute pharmacologic degradation via the
      previously described degradation tag (dTAG) system. Using different murine cell
      lines, we show here that the bifunctional molecule dTAG-7 induced rapid
      proteasome-dependent degradation of GFP-S8L-F12 and simultaneously increased its
      direct presentation on MHC class I molecules. Using the same model in a
      doxycycline-inducible setting, we could further show that stable, mature antigen
      was the major source of peptides presented, thereby excluding a dominant role of
      DRiPs in our system. This study is, to our knowledge, the first to investigate
      targeted pharmacologic protein degradation in the context of antigen presentation
      and our data point toward future applications by strategically combining
      therapies using bifunctional degraders with their stimulating effect on direct
      MHC class I presentation.

PMID- 29358940
TI  - Directed Differentiation of Human Induced Pluripotent Stem Cells into Dendritic
      Cells Displaying Tolerogenic Properties and Resembling the CD141+ Subset.
AB  - The advent of induced pluripotent stem cells (iPSCs) has begun to revolutionize
      cell therapy by providing a convenient source of rare cell types not normally
      available from patients in sufficient numbers for therapeutic purposes. In
      particular, the development of protocols for the differentiation of populations
      of leukocytes as diverse as naive T cells, macrophages, and natural killer cells
      provides opportunities for their scale-up and quality control prior to
      administration. One population of leukocytes whose therapeutic potential has yet
      to be explored is the subset of conventional dendritic cells (DCs) defined by
      their surface expression of CD141. While these cells stimulate cytotoxic T cells
      in response to inflammation through the cross-presentation of viral and tumor
      associated antigens in an MHC class I-restricted manner, under steady-state
      conditions CD141+ DCs resident in interstitial tissues are focused on the
      maintenance of homeostasis through the induction of tolerance to local antigens.
      Here, we describe protocols for the directed differentiation of human iPSCs into
      a mixed population of CD11c+ DCs through the spontaneous formation of embryoid
      bodies and exposure to a cocktail of growth factors, the scheduled withdrawal of
      which serves to guide the process of differentiation. Furthermore, we describe
      the enrichment of DCs expressing CD141 through depletion of CD1c+ cells, thereby
      obtaining a population of "untouched" DCs unaffected by cross-linking of surface
      CD141. The resulting cells display characteristic phagocytic and endocytic
      capacity and acquire an immunostimulatory phenotype following exposure to
      inflammatory cytokines and toll-like receptor agonists. Nevertheless, under
      steady-state conditions, these cells share some of the tolerogenic properties of
      tissue-resident CD141+ DCs, which may be further reinforced by exposure to a
      range of pharmacological agents including interleukin-10, rapamycin,
      dexamethasone, and 1alpha,25-dihydoxyvitamin D3. Our protocols therefore provide
      access to a novel source of DCs analogous to the CD141+ subset under steady-state
      conditions in vivo and may, therefore, find utility in the treatment of a range
      of disease states requiring the establishment of immunological tolerance.

PMID- 29358942
TI  - Ecophysiology and Growth of White Spruce Seedlings from Various Seed Sources
      along a Climatic Gradient Support the Need for Assisted Migration.
AB  - With climate change, favorable growing conditions for tree species are shifting
      northwards and to higher altitudes. Therefore, local populations are becoming
      less adapted to their environment. Assisted migration is one of the proposed
      adaptive measures to reduce the vulnerability of natural populations and maintain
      forest productivity. It consists of moving genetic material to a territory where
      future climate conditions correspond to those of its current location. Eight
      white spruce (Picea glauca [Moench] Voss) seed sources representing as many seed
      orchards were planted in 2013 at three forest sites simulating a south-north
      climatic gradient of 1.7 degrees C in Quebec, Canada. The objectives were to (1)
      evaluate the morpho-physiological responses of the different seed sources and (2)
      determine the role of genetic adaptation and physiological plasticity on the
      observed variation in morpho-physiological traits. Various seedling
      characteristics were measured, notably height growth from nursery to the fourth
      year on plantation. Other traits such as biomass and carbon allocation,
      nutritional status, and various photosynthetic traits before bud break, were
      evaluated during the fourth growing season. No interaction between sites and seed
      sources was observed for any traits, suggesting similar plasticity between seed
      sources. There was no change in the rank of seed sources and sites between years
      for height growth. Moreover, a significant positive correlation was observed
      between the height from the nursery and that after 4 years in the plantation.
      Southern seed sources showed the best height growth, while optimum growth was
      observed at the central site. Juvenile height growth seems to be a good indicator
      of the juvenile carbon sequestration and could serve as a selection criterion for
      the best genetics sources for carbon sequestration. Vector analysis showed no
      nitrogen deficiency 4 years after planting. Neither seed sources nor planting
      sites had a significant effect on photosynthesis before bud break. The observed
      results during the establishment phase under different site conditions indicate
      that southern seed sources may already benefit from assisted migration to cooler
      climatic conditions further north. While northern seed sources are likely to
      benefit from anticipated local global warming, they would not match the growth
      performance of seedlings from southern sources.

PMID- 29358943
TI  - Systematic Analysis of the Binding Surfaces between tRNAs and Their Respective
      Aminoacyl tRNA Synthetase Based on Structural and Evolutionary Data.
AB  - To determine the mechanism underlying the flow of genetic information, it is
      important to understand the relationship between a tRNA and its binding enzyme, a
      member of the aminoacyl-tRNA synthetase (aaRS) family. We have developed a novel
      method to project the interacting regions of tRNA-aaRS complexes, obtained from
      their three-dimensional structures, onto two-dimensional space. The interacting
      surface between each tRNA and its aaRS was successfully identified by determining
      these interactions with an atomic distance threshold of 3.3 A. We analyzed their
      interactions, using 60 mainly bacterial and eukaryotic tRNA-aaRS complexes, and
      showed that the tRNA sequence regions that interacted most strongly with each
      aaRS are the anticodon loop and the CCA terminal region, followed by the D-stem.
      A sequence conservation analysis of the canonical tRNAs was conducted in 83
      bacterial, 182 archaeal, and 150 eukaryotic species. Our results show that the
      three tRNA regions that interact with the aaRS and two additional loop regions (D
      loop and TPsiC-loop) known to be important for formation of the tRNA L-shaped
      structure are broadly conserved. We also found sequence conservations near the
      tRNA discriminator in the Bacteria and Archaea, and an enormous number of
      noncanonical tRNAs in the Eukaryotes. This is the first global view of tRNA
      evolution based on its structure and an unprecedented number of sequence data.

PMID- 29358944
TI  - A Powerful Gene-Based Test Accommodating Common and Low-Frequency Variants to
      Detect Both Main Effects and Gene-Gene Interaction Effects in Case-Control
      Studies.
AB  - Next-generation sequencing (NGS) has been widely used in genetic association
      studies to identify both common and rare variants associated with complex
      diseases. Various statistical association tests have been developed to analyze
      NGS data; however, most focus on identifying the marginal effects of a set of
      genetic variants on the disease. Only a few association tests for NGS data
      analysis have considered the interaction effects between genes. We developed
      three powerful gene-based gene-gene interaction tests for testing both the main
      effects and the interaction effects of common, low-frequency, and common with low
      frequency variant pairs between two genes (the IGOF tests) in case-control
      studies using NGS data. We performed a comprehensive simulation study to verify
      that the proposed tests had appropriate type I error rates and significantly
      higher power than did other interaction tests for analyzing NGS data. The tests
      were applied to a whole-exome sequencing dataset for autism spectrum disorder
      (ASD) and the significant results were evaluated in another independent ASD
      cohort. The IGOF tests were implemented in C++ and are available at
      http://igof.sourceforge.net.

PMID- 29358941
TI  - Methods of Controlling Invasive Fungal Infections Using CD8+ T Cells.
AB  - Invasive fungal infections (IFIs) cause high rates of morbidity and mortality in
      immunocompromised patients. Pattern-recognition receptors present on the surfaces
      of innate immune cells recognize fungal pathogens and activate the first line of
      defense against fungal infection. The second line of defense is the adaptive
      immune system which involves mainly CD4+ T cells, while CD8+ T cells also play a
      role. CD8+ T cell-based vaccines designed to prevent IFIs are currently being
      investigated in clinical trials, their use could play an especially important
      role in acquired immune deficiency syndrome patients. So far, none of the
      vaccines used to treat IFI have been approved by the FDA. Here, we review current
      and future antifungal immunotherapy strategies involving CD8+ T cells. We
      highlight recent advances in the use of T cells engineered using a Sleeping
      Beauty vector to treat IFIs. Recent clinical trials using chimeric antigen
      receptor (CAR) T-cell therapy to treat patients with leukemia have shown very
      promising results. We hypothesized that CAR T cells could also be used to control
      IFI. Therefore, we designed a CAR that targets beta-glucan, a sugar molecule
      found in most of the fungal cell walls, using the extracellular domain of Dectin
      1, which binds to beta-glucan. Mice treated with D-CAR+ T cells displayed
      reductions in hyphal growth of Aspergillus compared to the untreated group.
      Patients suffering from IFIs due to primary immunodeficiency, secondary
      immunodeficiency (e.g., HIV), or hematopoietic transplant patients may benefit
      from bioengineered CAR T cell therapy.

PMID- 29358945
TI  - Peroxisome Proliferator-Activated Receptors Associated with Nonalcoholic Fatty
      Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a major cause of
      chronic liver disease worldwide. Concurrent to an increase in NAFLD prevalence,
      there is an increase in the obesity epidemic and the correlated insulin-resistant
      state. It is a challenge to diagnose NAFLD because many patients are asymptomatic
      until the later stages of disease. The most common symptoms include fatigue,
      malaise, and discomfort in the right upper quadrant. The major and most accurate
      tool to clinically diagnose NAFLD is a liver biopsy, followed by histological
      analysis. However, this procedure is invasive and often carries a high risk of
      complications. Currently, there are no officially approved medications for the
      treatment of NAFLD. Although lifestyle modifications with proper diet and
      exercise have been shown to be beneficial, this has been difficult to achieve and
      sustain for many patients. Effective pharmacological treatments are still
      lacking; therefore, additional research to identify novel drugs is clearly
      warranted. PPARs are promising drug targets for the management of NAFLD and its
      related conditions of type 2 diabetes mellitus and cardiovascular disease. In
      this review, we provide an overview of recent studies on the association of PPARs
      and NAFLD.

PMID- 29358946
TI  - Prevalence of Anemia in Pediatric IBD Patients and Impact on Disease Severity:
      Results of the Pediatric IBD-Registry CEDATA-GPGE(r).
AB  - Aim: To determine the prevalence of anemia and its association with disease
      severity in children and adolescents with IBD. Methods: CEDATA-GPGE is a registry
      for pediatric patients with IBD in Germany and Austria from 90 specialized
      centers. As markers of disease severity, analysis included patient self
      assessment on a Likert scale (1-5; 1 = very good) and physicians' general
      assessment (0 = no activity to 4 = severe disease) and the disease indices.
      Anemia was defined as hemoglobin concentration below the 3rd percentile. Results:
      Prevalence of anemia was 65.2% in CD and 60.2% in UC. Anemic CD and UC patients
      showed significantly worse self-assessment than patients without anemia (average
      +/- standard deviation; CD: 3.0 +/- 0.9 versus 2.5 +/- 0.9, p < 0.0001; UC: 2.9
      +/- 0.9 versus 2.3 +/- 0.9, p < 0.0001). Accordingly, physicians' general
      assessment (PGA) was significantly worse in anemic than in nonanemic patients in
      CD (p < 0.0001) and UC (p < 0.0001). PCDAI in anemic CD, p < 0.0001, and PUCAI in
      anemic UC patients, p < 0.0001, were significantly higher than in nonanemic
      patients. 40.0% of anemic CD and 47.8% of anemic UC patients received iron during
      follow-up. Conclusion: Almost 2/3 of pediatric IBD patients are anemic. Patients'
      self-assessment and disease severity as determined by PGA and activity indices
      are worse in anemic patients. Contrastingly, only a minority received iron
      therapy.

PMID- 29358947
TI  - Anthropometric Measures and Frailty Prediction in the Elderly: An Easy-to-Use
      Tool.
AB  - Purpose: Anthropometry is a useful tool for assessing some risk factors for
      frailty. Thus, the aim of this study was to verify the discriminatory performance
      of anthropometric measures in identifying frailty in the elderly and to create an
      easy-to-use tool. Methods: Cross-sectional study: a subset from the
      Multidimensional Study of the Elderly in the Family Health Strategy (EMI-SUS)
      evaluating 538 older adults. Individuals were classified using the Fried
      Phenotype criteria, and 26 anthropometric measures were obtained. The predictive
      ability of anthropometric measures in identifying frailty was identified through
      logistic regression and an artificial neural network. The accuracy of the final
      models was assessed with an ROC curve. Results: The final model comprised the
      following predictors: weight, waist circumference, bicipital skinfold, sagittal
      abdominal diameter, and age. The final neural network models presented a higher
      ROC curve of 0.78 (CI 95% 0.74-0.82) (P < 0.001) than the logistic regression
      model, with an ROC curve of 0.71 (CI 95% 0.66-0.77) (P < 0.001). Conclusion: The
      neural network model provides a reliable tool for identifying prefrailty/frailty
      in the elderly, with the advantage of being easy to apply in the primary health
      care. It may help to provide timely interventions to ameliorate the risk of
      adverse events.

PMID- 29358948
TI  - The Tissue-Selective Estrogen Complex (Bazedoxifene/Conjugated Estrogens) for the
      Treatment of Menopause.
AB  - The tissue-selective estrogen complex (TSEC) pairs conjugated estrogens (CE) with
      a selective estrogen receptor modulator (SERM), bazedoxifene acetate (BZA). A 2
      year treatment with the TSEC improved vasomotor symptoms, quality of life, and
      vaginal atrophy in healthy postmenopausal women. In addition, the TSEC prevented
      vertebral and hip bone loss without increasing mammographic density, breast
      tenderness, the risk of myocardial infarction, stroke, or venous thromboembolism.
      Finally, the BZA 20 mg/CE 0.45 mg dose did not increase the risk of endometrial
      hyperplasia. Based on these findings, the TSEC can be considered as a first-line
      treatment for symptomatic postmenopausal women.

PMID- 29358949
TI  - Thyroid Isthmus Length and Iodine Turnover as Predictors of Successful
      Radioactive Iodine Therapy in Patients with Graves' Disease.
AB  - Radioactive iodine (RAI) therapy is an effective treatment option for Graves'
      disease. However, predicting treatment failures after RAI therapy remains
      controversial. The objective of this study was to investigate the factors
      associated with the success rate of RAI therapy for treatment of Graves'
      hyperthyroidism. Thyroid functional outcome, pre-RAI ultrasonographic features,
      and clinical parameters were evaluated retrospectively in 98 patients followed up
      for at least 12 months after RAI (mean RAI dose was 11.7 +/- 1.8 mCi).
      Hypothyroidism was achieved in 59 patients (60.2%), and euthyroidism in 16
      patients (16.3%), while 23 patients (23.5%) remained hyperthyroid. Age, sex, body
      mass index, pre-RAI thyroid function, or thyroid-stimulating immunoglobulin
      levels were not associated with treatment outcome. Length of thyroid isthmus (p =
      0.028) and 2- to 24-hour iodine uptake ratios (p = 0.002) were significantly
      associated with treatment failure, which was defined as a persistent hyperthyroid
      status after RAI therapy. Patients with a longer isthmus had a higher risk of
      remaining hyperthyroid, with a threshold for isthmus length of 5.2 mm, with a
      sensitivity of 69.6% and specificity of 70.3% for treatment success. Measuring
      the length of the thyroid isthmus can be a simple and useful way to predict RAI
      treatment outcome.

PMID- 29358950
TI  - Comparison of Exenatide and Metformin Monotherapy in Overweight/Obese Patients
      with Newly Diagnosed Type 2 Diabetes.
AB  - Aims: The present study assessed the therapeutic effect of exenatide and
      metformin as the initial therapy on overweight/obese patients with newly
      diagnosed type 2 diabetes (T2D). Methods: The prospective, nonrandomized,
      interventional study enrolled a total of 230 overweight or obese patients with
      newly diagnosed T2D who were administrated exenatide or metformin hydrochloride
      for 12 weeks. Results: 224/230 patients, including 106 in the exenatide group and
      118 in the metformin group, completed the 12-week treatment. Both exenatide and
      metformin significantly decreased the HbA1c levels in overweight/obese patients
      with newly diagnosed T2D (all P < 0.05). The reduction in HbA1c and the
      proportion of patients with HbA1c < 7.0% (53 mmol/mol) were higher in the
      exenatide group than in the metformin group (all P < 0.05). The exenatide
      treatment caused a greater decline in the body weight and BMI as compared to the
      metformin treatment (all P < 0.01). The exenatide treatment (beta = 0.41, P <
      0.01) and baseline HbA1c level (beta = -0.84, P < 0.01) were independent
      influencing factors for the decrease in HbA1c level. Conclusions: For an initial
      therapy in overweight/obese patients with newly diagnosed T2D, exenatide causes a
      better glycemic control than metformin. This trial is registered with
      NCT03297879.

PMID- 29358951
TI  - Persistence of Toxic Activity of Fermentation Extracts from Bacillus
      thuringiensis var. israelensis after More Than Three Decades of Storage.
AB  - This study was carried out to determine the persistence of toxicity of
      fermentation extracts of Bacillus thuringiensis var. israelensis after more than
      three decades of storage. For this purpose, a population of Aedes aegypti was
      established. The mortality rate of 20 spore-crystal extracts purified using the
      acetone-lactose coprecipitation method was measured and evaluated by bioassays
      according to a modified WHO protocol. The extracts with the highest mortality
      rate were determined in triplicate by their LD50 and LD98. All extracts showed
      toxicity at the highest tested dose (1000 ppm) and some, such as strains 3260 and
      3501, still killed larvae at doses as low as 0.01 ppm. These data are surprising
      because no study on the activity of B. thuringiensis toxic proteins after such a
      long storage time has been reported.

PMID- 29358952
TI  - Hepatoma-Derived Growth Factor Secreted from Mesenchymal Stem Cells Reduces
      Myocardial Ischemia-Reperfusion Injury.
AB  - Objectives: The present study aimed to explore the major factors that account for
      the beneficial effects of mesenchymal stem cells (MSCs). Methods: Using isobaric
      tags for relative and absolute quantitation method, hepatoma-derived growth
      factor (HDGF) was identified as an important factor secreted by MSCs, but not by
      cardiac fibroblasts (CFs). The protective effects of conditioned medium (CdM)
      from MSCs or CFs were tested by using either H9C2 cells that were exposed by
      hypoxia-reoxygenation (H/R) insult or an in vivo mouse model of myocardial
      ischemia-reperfusion. Results: Compared to CF-CdM, MSC-CdM conferred protection
      against reperfusion injury. CdM obtained from MSCs that were treated with HDGF
      targeted shRNA failed to offer any protection in vitro. In addition,
      administration of recombinant HDGF alone recapitulated the beneficial effects of
      MSC-CdM, which was associated with increased protein kinase C epsilon
      (PKCepsilon) phosphorylation, enhanced mitochondria aldehyde dehydrogenase family
      2 activity, and decreased 4-hydroxy-2-nonenal accumulation. A significant
      decrease in infarct size and ameliorated cardiac dysfunction was achieved by
      administration of HDGF in wild-type mice, which was absent in PKCepsilon dominant
      negative mice, indicating the essential roles of PKCepsilon in HDGF-mediated
      protection. Conclusions: HDGF secreted from MSCs plays a key role in the
      protection against reperfusion injury through PKCepsilon activation.

PMID- 29358953
TI  - Allogeneic Umbilical Cord-Derived Mesenchymal Stem Cells as a Potential Source
      for Cartilage and Bone Regeneration: An In Vitro Study.
AB  - Umbilical cord (UC) may represent an attractive cell source for allogeneic
      mesenchymal stem cell (MSC) therapy. The aim of this in vitro study is to
      investigate the chondrogenic and osteogenic potential of UC-MSCs grown onto
      tridimensional scaffolds, to identify a possible clinical relevance for an
      allogeneic use in cartilage and bone reconstructive surgery. Chondrogenic
      differentiation on scaffolds was confirmed at 4 weeks by the expression of sox-9
      and type II collagen; low oxygen tension improved the expression of these
      chondrogenic markers. A similar trend was observed in pellet culture in terms of
      matrix (proteoglycan) production. Osteogenic differentiation on bone-graft
      substitute was also confirmed after 30 days of culture by the expression of
      osteocalcin and RunX-2. Cells grown in the hypertrophic medium showed at 5 weeks
      safranin o-positive stain and an increased CbFa1 expression, confirming the
      ability of these cells to undergo hypertrophy. These results suggest that the UC
      MSCs isolated from minced umbilical cords may represent a valuable allogeneic
      cell population, which might have a potential for orthopaedic tissue engineering
      such as the on-demand cell delivery using chondrogenic, osteogenic, and
      endochondral scaffold. This study may have a clinical relevance as a future
      hypothetical option for allogeneic single-stage cartilage repair and bone
      regeneration.

PMID- 29358954
TI  - The Role of Nephronectin on Proliferation and Differentiation in Human Dental
      Pulp Stem Cells.
AB  - Aim: The purpose of the current study was to investigate the effects of
      nephronectin (Npnt) in human dental pulp stem cells (hDPSCs). Methodology: Npnt
      was coated to nontissue culture-treated polystyrene (non-PS) plates. The presence
      of immobilized protein on the surface was detected by polyclonal rabbit primary
      anti-Npnt antibody. Then the cell number was counted and compared with PBS-,
      bovine serum albumin- (BSA-), fish scale type I collagen- (FCOL1-), and human
      fibronectin- (Fn-) coated wells. Cell proliferation was assessed using CCK-8
      assay. Cell morphology was observed under light microscopy and fluorescence
      microscopy. Lastly, the mRNA expression profiles of integrins, dentin
      sialophosphoprotein (DSPP), bone sialoprotein (BSP), and mineralization capacity
      of hDPSCs were investigated by real time RT-PCR and alizarin red staining,
      respectively. Results: Npnt mediates hDPSC adhesion and spreading partially via
      the Arg-Gly-Asp (RGD) motif. Npnt enhanced the mRNA expression of ITGA1, ITGA4,
      ITGA7, and ITGB1 on day five. Npnt downregulated DSPP but significantly
      upregulated BSP mRNA expression at day 28. Further, Npnt and FCOL1 accelerated
      the matrix mineralization in hDPSCs. Conclusions: The current findings implicate
      that Npnt would be favorable to recruit hDPSCs and conducive to mineralization in
      hDPSCs. The combination of Npnt with hDPSCs may offer a promising approach for
      hard tissue regeneration.

PMID- 29358955
TI  - A Molecular and Clinical Review of Stem Cell Therapy in Critical Limb Ischemia.
AB  - Peripheral artery disease (PAD) is one of the major vascular complications in
      individuals suffering from diabetes and in the elderly that can progress to
      critical limb ischemia (CLI), portending significant burden in terms of patient
      morbidity and mortality. Over the last two decades, stem cell therapy (SCT) has
      risen as an attractive alternative to traditional surgical and/or endovascular
      revascularization to treat this disorder. The primary benefit of SCT is to induce
      therapeutic neovascularization and promote collateral vessel formation to
      increase blood flow in the ischemic limb and soft tissue. Existing evidence
      provides a solid rationale for ongoing in-depth studies aimed at advancing
      current SCT that may change the way PAD/CLI patients are treated.

PMID- 29358958
TI  - Extracellular Vesicles from Adipose-Derived Mesenchymal Stem/Stromal Cells
      Accelerate Migration and Activate AKT Pathway in Human Keratinocytes and
      Fibroblasts Independently of miR-205 Activity.
AB  - Mesenchymal stem/stromal cells (MSCs) are promising tools in cell therapy. They
      secrete extracellular vesicles (EVs) that carry different classes of molecules
      that can promote skin repair, but the mechanisms are poorly understood. Skin
      wound healing is a complex process that requires the activity of several
      signaling pathways and cell types, including keratinocytes and fibroblasts. In
      this study, we explored whether adipose tissue MSC-derived EVs could accelerate
      migration and proliferation of keratinocytes and fibroblasts, activate the AKT
      pathway, and promote wound healing in vivo. Furthermore, we evaluated if EV
      effects are miR-205 dependent. We found that MSC EVs had an average diameter of
      135 nm. Keratinocytes and fibroblasts exposed to EVs exhibited higher levels of
      proliferation, migration, and AKT activation. Topical administration of EVs
      accelerated skin wound closure. Knockdown of miR-205 decreased AKT
      phosphorylation in fibroblasts and keratinocytes, whereas migration was decreased
      only in keratinocytes. Moreover, knockdown of miR-205 failed to inhibit AKT
      phosphorylation in fibroblasts and keratinocytes exposed to EVs. About the
      mechanism of EV effects, we found that incubation with EVs prevented inhibition
      of AKT activation by miR-205 knockdown, suggesting that EVs activate AKT
      independently of miR-205. In conclusion, we demonstrated that EVs are a promising
      tool for wound healing.

PMID- 29358957
TI  - The Effects of Different Factors on the Behavior of Neural Stem Cells.
AB  - The repair of central nervous system (CNS) injury has been a worldwide problem in
      the biomedical field. How to reduce the damage to the CNS and promote the
      reconstruction of the damaged nervous system structure and function recovery has
      always been the concern of nerve tissue engineering. Multiple differentiation
      potentials of neural stem cell (NSC) determine the application value for the
      repair of the CNS injury. Thus, how to regulate the behavior of NSCs becomes the
      key to treating the CNS injury. So far, a large number of researchers have
      devoted themselves to searching for a better way to regulate the behavior of
      NSCs. This paper summarizes the effects of different factors on the behavior of
      NSCs in the past 10 years, especially on the proliferation and differentiation of
      NSCs. The final purpose of this review is to provide a more detailed theoretical
      basis for the clinical repair of the CNS injury by nerve tissue engineering.

PMID- 29358956
TI  - Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and
      Cancer.
AB  - MTG16 (myeloid translocation gene on chromosome 16) and its related proteins,
      MTG8 and MTGR1, define a small family of transcriptional corepressors. These
      corepressors share highly conserved domain structures yet have distinct
      biological functions and tissue specificity. In vivo studies have shown that, of
      the three MTG corepressors, MTG16 is uniquely important for the regulation of
      hematopoietic stem/progenitor cell (HSPC) proliferation and differentiation.
      Apart from this physiological function, MTG16 is also involved in carcinomas and
      leukemias, acting as the genetic target of loss of heterozygosity (LOH)
      aberrations in breast cancer and recurrent translocations in leukemia. The
      frequent involvement of MTG16 in these disease etiologies implies an important
      developmental role for this transcriptional corepressor. Furthermore, mounting
      evidence suggests that MTG16 indirectly alters the disease course of several
      leukemias via its regulatory interactions with a variety of pathologic fusion
      proteins. For example, a recent study has shown that MTG16 can repress not only
      wild-type E2A-mediated transcription, but also leukemia fusion protein E2A-Pbx1
      mediated transcription, suggesting that MTG16 may serve as a potential
      therapeutic target in acute lymphoblastic leukemia expressing the E2A-Pbx1 fusion
      protein. Given that leukemia stem cells share similar regulatory pathways with
      normal HSPCs, studies to further understand how MTG16 regulates cell
      proliferation and differentiation could lead to novel therapeutic approaches for
      leukemia treatment.

PMID- 29358959
TI  - A Review on the Cosmeceutical and External Applications of Nigella sativa.
AB  - It is estimated by the World Health Organization (WHO) that most of the world's
      population depends on herbal medicine for their health care. Nigella sativa (N.
      sativa), also known as black-caraway and as "Kalonji," is a well-known seed all
      over the world. It is one of the most common medicinal plants worldwide and
      contains many useful chemical constituents that we can find in its fixed oil,
      such as thymoquinone, thymohydroquinone, dithymoquinone, thymol, nigellicine,
      carvacrol, nigellimine, nigellicine, nigellidine, and alpha-hederin. Due to these
      numerous important ingredients it was found that it affects different areas of
      our body and has many pharmacological effects as antibacterial, antiviral, anti
      inflammatory, and wound healing effect and also for acne vulgaris, skin cancer,
      pigmentation, and many cosmeceutical applications. Based on the folklore usage of
      N. sativa seeds and oil, they are used in various systems of food and medicines.
      The aim of this article is to provide a detailed survey of the literature of
      cosmeceutical and external applications of N. sativa which is expected to
      stimulate further studies on this subject.

PMID- 29358960
TI  - Electroacupuncture is Beneficial for Primary Dysmenorrhea: The Evidence from Meta
      Analysis of Randomized Controlled Trials.
AB  - Electroacupuncture (EA) is considered to be a promising alternative therapy to
      relieve the menstrual pain for primary dysmenorrhea (PD), but the conclusion is
      controversial. Here, we conducted a systematic review and meta-analysis
      specifically to evaluate the clinical efficacy from randomized controlled trials
      (RCTs) on the use of EA in patients with PD. PubMed, Embase, ISI Web of Science,
      CENTRAL, CNKI, and Wanfang were searched to identify RCTs that evaluated the
      effectiveness of EA for PD. The outcome measurements included visual analogue
      scale (VAS), verbal rating scale (VRS), COX retrospective symptom scale (RSS),
      and the curative rate. Nine RCTs with high risk of bias were included for meta
      analysis. The combined VAS 30 minutes after the completion of intervention
      favoured EA at SP6 when compared with EA at GB39, nonacupoints, and waiting-list
      groups. EA was superior to pharmacological treatment when the treatment duration
      lasted for three menstrual cycles, evidenced by significantly higher curative
      rate. No statistically significant differences between EA at SP6 and control
      groups were found regarding the VRS, RSS-COX1, and RSS-COX2. The findings of our
      study suggested that EA can provide considerable immediate analgesia effect for
      PD. Additional studies with rigorous design and larger sample sizes are needed.

PMID- 29358961
TI  - Antipruritic Effect of Acupuncture in Patients with Atopic Dermatitis:
      Feasibility Study Protocol for a Randomised, Sham-Controlled Trial.
AB  - This study aims to test the feasibility of a randomised clinical trial to
      evaluate how acupuncture affects atopic dermatitis (AD) symptoms and quality of
      life and to explore potential biomarkers that may be associated with AD. It is a
      sham-controlled trial in which 30 eligible patients will be randomly allocated in
      a 1 : 1 : 1 ratio to one of three groups: verum acupuncture (VA) group 1 (3 times
      weekly for 4 weeks); VA group 2 (twice weekly for 4 weeks); or sham acupuncture
      group (SA; twice weekly for 4 weeks). SA will consist of nonpenetrating
      acupuncture. Outcome measures will include the Visual Analogue Scale for itch,
      SCORing Atopic Dermatitis, and Eczema Area and Severity Index to evaluate AD
      symptoms improvement along with the Patient Oriented Eczema Measure and
      Dermatology Life Quality Index to assess quality of life. Measures will be
      collected at baseline, once weekly during the treatment period, and after a 4
      week follow-up period. Blood collection will be at baseline and 4 and 8 weeks
      after treatment and compared with healthy controls. Illumina sequencing will be
      used to profile microRNA expression in each group to explore candidate microRNA
      biomarkers for specific effects of acupuncture in patients with AD. This trial is
      registered via US National Institutes of Health Clinical Trials registry
      (ClinicalTrials.gov) on 15 July 2016, identifier: NCT02844452.

PMID- 29358962
TI  - Inhibitory Activity of Ficus deltoidea var. trengganuensis Aqueous Extract on
      Lipopolysaccharide-Induced TNF-alpha Production from Microglia.
AB  - Objective: To explore the effect of Ficus deltoidea (FD) aqueous extracts on the
      release of tumor necrosis factor-alpha (TNF-alpha), the expression of CD40, and
      the morphology of microglial cells in lipopolysaccharide- (LPS-) activated BV2
      cells. Methods: The cytotoxicity of FD extract was assessed by MTS solution. BV2
      cells were divided into 5 experimental groups, intervened, respectively, by FD (4
      mg/mL) and LPS + FD (0, 1, 2, and 4 mg/mL). Besides, a blank control group was
      set up without any intervention. TNF-alpha release was assessed by enzyme linked
      immunosorbent assay (ELISA). The expression of CD40 was examined by flow
      cytometry. Immunocytochemical staining was used to show the morphology of BV2
      cells. Results: FD extract of different concentrations (1, 2, and 4 mg/mL) had no
      significant toxic effects on the BV2 cells. FD suppressed the activation of
      microglia in morphology and reduced TNF-alpha production and expression of CD40
      induced by LPS. Conclusion: FD extract has a therapeutic potential against
      neuroinflammatory diseases.

PMID- 29358963
TI  - Compound Wumei Powder Inhibits the Invasion and Metastasis of Gastric Cancer via
      Cox-2/PGE2-PI3K/AKT/GSK3beta/beta-Catenin Signaling Pathway.
AB  - To explore the role of CWP in invasion and migration of gastric cancer cells and
      its underlying molecular mechanism, we performed the experiment in SGC-7901 cells
      both in vitro and in vivo. In the cell experiment, we evaluated cell
      proliferation by MTT assay. The results showed that CWP can inhibit the growth of
      SGC-7901 cells. The influence on cell migration and invasion was detected by
      wound-healing and Transwell invasion assays. The results showed that the
      abilities of invasion and migration are restrained in CWP group. Western blot
      showed that CWP can decrease the expression of Cox-2 and inhibit the
      PI3K/AKT/GSK3beta/beta-catenin signaling pathway. In the animal experiment, we
      observed that CWP had an inhibitory effect on the growth of xenograft tumors of
      nude mice. IHC assay, ELISA, RT-PCR assay, and Western blot assay were used to
      test relevant cytokines of Cox-2/PGE2-PI3K/AKT/GSK3beta/beta-catenin pathway. The
      results showed that CWP can suppress relevant cytokines of Cox-2/PGE2
      PI3K/AKT/GSK3beta/beta-catenin pathway. In conclusion, we suggest that CWP
      inhibits the invasion and metastasis of SGC-7901 cells via Cox-2/PGE2
      PI3K/AKT/GSK3beta/beta-catenin signaling pathway.

PMID- 29358965
TI  - Retracted: Herbal Supplement Ameliorates Cardiac Hypertrophy in Rats with CCl4
      Induced Liver Cirrhosis.
AB  - [This retracts the article DOI: 10.1155/2012/139045.].

PMID- 29358964
TI  - The Effect of Auricular Acupoint Stimulation in Overweight and Obese Adults: A
      Systematic Review and Meta-Analysis of Randomized Controlled Trials.
AB  - Objective: To investigate the effect of auricular acupoint stimulation on
      overweight and obese adults. Methods: We searched databases including PubMed,
      EMBASE, Allied and Complementary Medicine Database, National Knowledge
      Infrastructure, and the PerioPath Index to Taiwan Periodical Literature. The
      modified Jadad scale was used to assess study quality. We investigated the effect
      of auricular acupoint stimulation on anthropometric measurements. Results:
      Eighteen randomized controlled trials (RCTs) were included in our systematic
      review. Thirteen RCTs were pooled in a meta-analysis that revealed a significant
      reduction in body weight (BW) with a mean difference (MD) of -1.21 kg and a 95%
      confidence interval (CI) from -1.94 to -0.47 with a heterogeneity of I2 = 88%.
      Significant decreases in body mass index (BMI; MD: -0.57 kg/m2; 95% CI -0.82 to 
      0.33; I2 = 78%), body fat (BF; MD: -0.83%; 95% CI -1.43 to -0.24; I2 = 0%), and
      waist circumference (WC; MD: -1.75 cm; 95% CI -2.95 to -0.55; I2 = 87%) were also
      revealed. Conclusions: This meta-analysis shows that auricular acupoint
      stimulation improves physical anthropometric parameters including BW, BMI, BF,
      and WC in overweight and obese adults. These methods are less effective on hip
      circumference and waist-to-hip ratio.

PMID- 29358966
TI  - Changes in Nitric Oxide Releases of the Contralateral Acupoint during and after
      Laser Acupuncture at Bilateral Same-Name Acupoints in Human.
AB  - Objective: The purpose of the study was to examine the effects of laser
      acupuncture (LA) at right Neiguan (RPC6)/left Neiguan (LPC6) acupoints on the
      releases of nitric oxide (NO) in the treated and contralateral/nontreated PC6,
      compared to the nonacupoint control area. Methods: 24 mW LA at RPC6, LPC6, and
      nonacupoint in 22 healthy subjects for 40 min: sterilized dialysis tube was taped
      to the nontreated PC6/nonacupoint during the treatment and immediately taped to
      the treated and nontreated PC6/nonacupoint after LA removal. NO-scavenging
      compound was injected into the tube for 40 min to absorb the molecular which was
      tested by spectrophotometry in a blinded fashion. Results: LA-induced NO releases
      over PC6 acupoints for the nontreated and treated sides all significantly
      increased after LA removal, but for the nontreated acupoints they did not change
      during LA stimulation. LA at RPC6 induced the more release of the NO at
      contralateral side than stimulating LPC6, but not on nonacupoints. The results
      suggest that LA-induced NO release over contralateral acupoint and NO release
      resulting from the lateralized specificity all are different and specific to the
      acupoint within different time course. Conclusions: LA-evoked NO release over
      acupoints could improve the neurogenic, endothelial activity of the vessel wall
      to further facilitate microcirculation.

PMID- 29358967
TI  - Corrigendum to "Autophagy Inhibition Enhances Apoptosis Induced by Dioscin in
      Huh7 Cells".
AB  - [This corrects the article DOI: 10.1155/2012/134512.].

PMID- 29358968
TI  - Methanol Extract of Holarrhena antidysenterica Inhibits the Growth of Human Oral
      Squamous Cell Carcinoma Cells and Osteoclastogenesis of Bone Marrow Macrophages.
AB  - Oral squamous cell carcinoma (OSCC) frequently invades mandibular bone, and
      outcomes for treatment with surgical resection are typically poor, ultimately
      resulting in death. Holarrhena antidysenterica L. (Apocynaceae), distributed
      throughout Sri Lanka and India, has been used as a folk remedy to treat various
      diseases. Treatment with methanol extract of H. antidysenterica bark (HABE)
      inhibited cell viability and BrdU incorporation and induced apoptotic cell death
      in Ca9-22 gingival and HSC-3 tongue SCC cells. Flow cytometric analysis indicated
      that HABE treatment preferentially induces apoptotic cell death via increasing
      the sub-G1 peak in Ca9-22 cells and cell cycle arrest at the G1 phase in HSC-3
      cells. HABE treatment in the presence of zVAD-fmk, a pan-caspase inhibitor,
      rescued cell viabilities in both OSCC cell lines. The ratio of Bax to Bcl-2
      increased with reductions in the Bcl-2 protein expression, and the activation of
      caspase 3 and subsequent cleavage of PARP was detected in HABE-treated Ca9-22 and
      HSC-3 cells. Furthermore, HABE treatment at noncytotoxic concentrations inhibited
      osteoclast formation in RANKL-stimulated bone marrow macrophages. Taken together,
      HABE possesses the inhibitory activity on the growth of OSCC cells and
      antiosteoclastogenic activity. Therefore, HABE may be a promising alternative and
      complementary agent for preventing and treating OSCC.

PMID- 29358969
TI  - A New Chinese Medicine Intestine Formula Greatly Improves the Effect of
      Aminosalicylate on Ulcerative Colitis.
AB  - Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon.
      Current medical treatment of UC relies predominantly on the use of traditional
      drugs, including aminosalicylates, corticosteroids, and immunosuppressants, which
      failed to effectively control this disease's progression and produced various
      side effects. Here, we report a new Chinese medicine intestine formula (CIF)
      which greatly improved the effect of mesalazine, an aminosalicylate, on UC. In
      the present study, 60 patients with chronic UC were treated with oral mesalazine
      alone or in combination with CIF enema. The combination of mesalazine and CIF
      greatly and significantly improved the clinical symptoms and colon mucosal
      condition and improved the Mayo Clinic Disease Activity Index and health-related
      quality of life, when compared to mesalazine alone. In particular, the addition
      of CIF further decreased serum levels of tumor necrosis factor-alpha and
      hypersensitivity C-reactive protein but in contrast increased interleukin-4.
      Thus, the results demonstrate the beneficial role of CIF in UC treatment, which
      may be mediated by the regulation of inflammation.

PMID- 29358970
TI  - Electroacupuncture Inhibits the Activation of p38MAPK in the Central Descending
      Facilitatory Pathway in Rats with Inflammatory Pain.
AB  - The mitogen-activated protein kinases (MAPKs), especially p38MAPK, play a pivotal
      role in chronic pain. Electroacupuncture (EA) relieves inflammatory pain
      underlying the descending pathway, that is, the periaqueductal gray (PAG), the
      rostral ventromedial medulla (RVM), and the spinal cord dorsal horn (SCDH).
      However, whether EA antagonizes inflammatory pain through regulation of p38MAPK
      in this descending facilitatory pathway is unclear. Complete Freund's adjuvant
      (CFA) was injected into the hind paw of rats to establish inflammatory pain
      model. EA was administrated for 30 min at Zusanli and Kunlun acupoints at 0.5,
      24.5, 48.5, and 72.5 h, respectively. The paw withdrawal threshold (PWT), paw
      edema, and Phosphor-p38MAPK-Immunoreactivity (p-p38MAPK-IR) cells were measured
      before (0 h) and at 1, 3, 5, 7, 25, and 73 h after CFA or saline injection. EA
      increased PWT at 1, 3, 25, and 73 h and inhibited paw edema at 25 and 73 h after
      CFA injection. Moreover, the increasing number of p-p38MAPK-IR cells which was
      induced by CFA was suppressed by EA stimulation in PAG and RVM at 3 and 5 h and
      in SCDH at 5, 7, 25, and 73 h. These results suggest that EA suppresses
      inflammation-induced hyperalgesia probably through inhibiting p38MAPK activation
      in the descending facilitatory pathway.

PMID- 29358971
TI  - Effects of Shizhifang on NLRP3 Inflammasome Activation and Renal Tubular Injury
      in Hyperuricemic Rats.
AB  - Objective: Uric acid (UA) activates the NLRP3-ASC-caspase-1 axis and triggers
      cascade inflammatory that leads to hyperuricemic nephropathy and hyperuricemia
      induced renal tubular injury. The original study aims to verify the positive
      effects of the traditional Chinese medicinal formula Shizhifang (SZF) on
      ameliorating the hyperuricemia, tubular injury, and inflammasome infiltration in
      the kidneys of hyperuricemic lab rats. Method: Twenty-eight male Sprague-Dawley
      rats were divided into four groups: control group, oxonic acid potassium (OA)
      model group, OA + SZF group, and OA + Allopurinol group. We evaluated the
      mediating effects of SZF on renal mitochondrial reactive oxygen species (ROS) and
      oxidative stress (OS) products, protein expression of NLRP3-ASC-caspase-1 axis,
      and downstream inflammatory factors IL-1beta and IL-18 after 7 weeks of animals
      feeding. Result: SZF alleviated OA-induced hyperuricemia and inhibited OS in
      hyperuricemic rats (P < 0.05). SZF effectively suppressed the expression of gene
      and protein of the NLRP3-ASC-caspase-1 axis through accommodating the ROS-TXNIP
      pathway (P < 0.05). Conclusion: Our data suggest that SZF alleviates renal
      tubular injury and inflammation infiltration by inhibiting NLRP3 inflammasome
      activation triggered by mitochondrial ROS in the kidneys of hyperuricemic lab
      rats.

PMID- 29358972
TI  - Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia
      in the Chronic Constriction Injury Model of Rats.
AB  - Neuropathic pain is common in clinical practice. Exploration of new drug
      therapeutics has always been carried out for more satisfactory effects and fewer
      side-effects. In the present study, we aimed to investigate effects of Tongluo
      Zhitong Prescription (TZP), a compounded Chinese medicine description, on
      neuropathic pain model of rats with chronic constriction injury (CCI). The CCI
      model was established by loosely ligating sciatic nerve with catgut suture,
      proximal to its trifurcation. The static and dynamic allodynia, heat
      hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our
      results showed that TZP alleviated CCI-induced static and dynamic allodynia,
      suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait
      function. These results suggest that TZP could alleviate neuropathic pain.
      Further experiments are needed to explore its mechanisms.

PMID- 29358973
TI  - Corrigendum to "Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied
      with Suppression of Wnt/beta-Catenin Signaling and Apoptosis Induction".
AB  - [This corrects the article DOI: 10.1155/2013/146136.].

PMID- 29358974
TI  - Immunoenhancement of Edible Fungal Polysaccharides (Lentinan, Tremellan, and
      Pachymaran) on Cyclophosphamide-Induced Immunosuppression in Mouse Model.
AB  - Fungal polysaccharides display a variety of important biological activities,
      including anti-inflammatory, antitumor, and immune-stimulating activities. The
      aim of present study was to investigate the immunomodulatory effect of fungal
      polysaccharides on cyclophosphamide-induced immunosuppression in mice. Mice were
      pretreated orally with lentinan, tremellan, pachymaran, or a mixture of the
      three, respectively. The results showed that pretreatments with polysaccharides
      significantly increased the thymus index in cyclophosphamide-induced
      immunosuppression mice. The level of the cytokine IL-10 in sera of
      cyclophosphamide-induced mice was decreased after pretreatments of
      polysaccharides. Flow cytometry results showed that pretreatments with
      polysaccharides enhanced the phagocytosis of peritoneal macrophages in mice. The
      increased levels of serum antibody IgG and IgM were observed in the groups
      pretreated with polysaccharides. Our work demonstrated that the treatment of
      polysaccharides elicited strong immune activity and a protective effect against
      cyclophosphamide-induced immunosuppression.

PMID- 29358976
TI  - Organic Creativity for Well-Being in the Post-Information Society.
AB  - The editorial dwells upon the technology-driven evolution from the Industrial to
      the Post-Information Society, indicating that this transition will bring about
      drastic transformations in our way of living, starting from the job market and
      then pervading all aspects at both individual and social levels. Great
      opportunities will come together with unprecedented challenges to living as we
      have always known it. In this innovation-filled scenario, it is argued that human
      creativity becomes the distinctive ability to provide dignity at first and
      survival in the long term. The term organic creativity is introduced to indicate
      those conditions, attitudes, and actions that bear the potential to be at the
      same time productive in socio-economic terms and conducive to human well-being.
      As a consequence, the role of psychologists in an open cooperation with
      sociologists, economists, computer scientists, engineers and others, will be as
      central as ever in establishing healthy collaboration modes between humans and
      machines, and large investments in related multidisciplinary scientific research
      are advocated to establish organic creativity as a discipline that should
      permeate every educational level, as well as our professional and everyday lives.

PMID- 29358975
TI  - Changes in Coping, Autonomous Motivation, and Beliefs about Exercise among Women
      in Early Recovery from Alcohol Participating in a Lifestyle Physical Activity
      Intervention.
AB  - Women are particularly likely to drink alcohol for the purpose of coping with or
      alleviating negative affect. Engaging in physical activity has been posited as a
      potentially effective alternate coping strategy during early recovery for
      managing mood and cravings. Utilizing exercise to cope may be associated with
      more adaptive coping strategies in general. Additionally, an intrinsic
      (autonomous) motivational style and positive beliefs about exercise are
      associated with long-term adherence to physical activity. The current study
      evaluates changes in coping strategies, autonomous motivation, and beliefs about
      exercise among women engaged in a physical activity intervention during early
      recovery (N=20; mean age=39.53). General coping strategies, motivational style,
      and beliefs about exercise were examined before and after engaging in the 12-week
      intervention which aimed to help women utilize physical activity as a means to
      cope with negative affect and alcohol craving. We found that, by the end of the
      intervention, participants significantly increased utilization of adaptive coping
      strategies such as the use of emotional support from others. Additionally,
      participants increased autonomous motivation over time. There were no significant
      changes in beliefs about exercise. Changes in beliefs about benefits of exercise,
      autonomous motivation, and adaptive coping were related to use of exercise to
      cope. However, even though these changes were associated with how women in the
      intervention used exercise, they were not associated with exercising more.
      Results from this open pilot suggest that women in early recovery from alcohol
      who increase physical activity - specifically as a means to cope with negative
      affect and craving - also demonstrate other wider coping strategies, more
      positive beliefs, and autonomous motivation.

PMID- 29358977
TI  - Compassionate Love for a Romantic Partner Across the Adult Life Span.
AB  - Compassionate love has received research attention over the last decade, but it
      is as yet unclear how it is experienced over a lifetime. The purpose of this
      study was to investigate compassionate love for a romantic partner throughout the
      adult life span, exploring individual differences in the propensity to experience
      compassionate love in regard to age, gender, religion, love status, love styles,
      and subjective well-being. The results showed that religion and love status
      display significant effects on compassionate love. Believers experienced greater
      compassionate love than nonbelievers, and individuals in love presented greater
      compassionate love than those who were not in love. Love styles and subjective
      well-being were found to be related to compassionate love. These findings
      corroborate studies that indicate that individuals who experience higher
      compassionate love for a romantic partner are more likely to report Eros, Agape,
      and subjective well-being.

PMID- 29358978
TI  - The Effects of Maltreatment in Childhood on Working Memory Capacity in Adulthood.
AB  - The aim of this study was to research the relation between exposure to
      maltreatment in childhood and working memory capacity in adulthood. A survey
      among 376 females in the age between 16 and 67 was administered. Exposure to
      maltreatment in childhood (sexual, physical and psychological abuse, neglect and
      witnessing family violence) was assessed retrospectively using the Child
      Maltreatment Questionnaire (Karlovic, Buljan-Flander, & Vranic, 2001), whilst the
      Working Memory Questionnaire (Vallat-Azouvi, Pradat-Diehl, & Azouvi, 2012) was
      used to assess working memory capacity (recalling verbal information, numerical
      information, attention ability and executive functioning). The results suggest a
      significantly greater prevalence of physical abuse and witnessing family violence
      in comparison to other forms of maltreatment in childhood. Psychological abuse
      and witnessing family violence have shown themselves to be statistically
      significant predictors for deficits in total working memory capacity, verbal
      recall and attention ability. The results suggest that traumatic experiences
      during childhood, such as abuse, may trigger particular cognitive changes which
      may be reflected in adulthood. It is, therefore, exceedingly important to conduct
      further research in order to contribute to the understanding of the correlation
      between cognitive difficulties and maltreatment in childhood.

PMID- 29358979
TI  - The Effect of Telling Lies on Belief in the Truth.
AB  - The current study looks at the effect of telling lies, in contrast to simply
      planning lies, on participants' belief in the truth. Participants planned and
      told a lie, planned to tell a lie but didn't tell it, told an unplanned lie, or
      neither planned nor told a lie (control) about events that did not actually
      happen to them. Participants attempted to convince researchers that all of the
      stories told were true. Results show that telling a lie plays a more important
      role in inflating belief scores than simply preparing the script of a lie.
      Cognitive dissonance may lead to motivated forgetting of information that does
      not align with the lie. This research suggests that telling lies may lead to
      confusion as to the veracity of the lie leading to inflated belief scores.

PMID- 29358980
TI  - The Effect of Schooling on Basic Cognition in Selected Nordic Countries.
AB  - The present study investigated schooling effects on cognition. Cognitive data
      were collected as part of a research project (ProMeal) that investigated school
      meals and measured the intake of school lunch in relation to children's health,
      cognitive function, and classroom learning in four Nordic countries, among
      children between 10-11 years of age. It was found that Finnish pupils attending
      4th grade were not, on any measure, outperformed by Norwegian and Icelandic
      pupils attending 5th and Swedish pupils attending 4th grade on a task measuring
      working memory capacity, processing speed, inhibition, and in a subsample on
      response- and attention control. Moreover, boys were found to perform superior to
      girls on tasks measuring processing speed. However, girls were found to perform
      better on tasks related to attention and self-control. The results are discussed
      in relation to the reciprocal association between cognition and schooling and
      whether these results reflect quality differences between schools in the four
      Nordic countries; most notably in comparison to Finland.

PMID- 29358981
TI  - Moral Foundations and Voting Intention in Italy.
AB  - Based on the view of morality proposed by the Moral Foundations Theory, this
      paper investigates whether voting intention is associated with moral foundation
      endorsement in not perfectly bipolar electoral contexts. Three studies carried
      out in Italy from 2010 to 2013, showed that controlling for ideological
      orientation, moral foundation endorsement is associated with voting intention. In
      Study 1 and 3, in fictitious and real national elections, intention to vote for
      right-wing political groups rather than for left-wing rivals was associated with
      Sanctity, confirming previous results obtained in the U.S. Furthermore, as a
      function of the specific competing political groups in each of the examined
      contexts other moral foundations predicted voting intention. In Study 1, Care and
      Authority predicted voting intention for the major political groups rather than
      for an autonomist party that aimed at decreasing central government's fiscal
      power in favor of fiscal regional autonomy. In Study 3, Loyalty predicted the
      intention to vote for the major parliamentarian parties rather than for a
      movement that aimed at capturing disaffection towards traditional politics. In
      Study 2, at real regional elections, Loyalty predicted voting intention for the
      incumbent right-wing governor rather than for the challengers and Fairness
      predicted voting intention for left-wing extra-parliamentarian political groups
      rather than for the major left-wing party. Thus multiple moral concerns can be
      associated with voting intention. In fragmented and unstable electoral contexts,
      at each election the context of the competing political groups may elicit
      specific moral concerns that can contribute to affect voting intention beyond
      ideological orientation.

PMID- 29358982
TI  - Muslim Immigrant Men's and Women's Attitudes Towards Intimate Partner Violence.
AB  - This study aims to study the attitudes towards Intimate Partner Violence (IPV) in
      a group of Muslim immigrants. To this end, six focus-groups were conducted
      involving 42 first-generation Muslim immigrants (21 males and 21 females) from
      Pakistan, Egypt and Morocco. Focus groups transcripts were then analyzed using
      the software ATLAS.ti. Irrespectively of nationality, couples replicate
      relational models learnt in their country of origin, implying a rigid gender
      based role division. Women are considered less socially competent if compared to
      men and therefore in need of protection. Divorce is possible only in case of
      severe danger: women have to stand beside their husbands and maintain family
      unity. Even though they are not directly related to IPV, these factors may be key
      in determining its onset and perpetration. With regards to ethnic background,
      Pakistani interviewees not only seem to acknowledge the possible occurrence of
      violence within couple relationships, they also accept it as a mean to regulate
      socially dysfunctional behaviors. Both Moroccan males and females denounce the
      impact of post migration stressors as potential triggers of IPV. The distance
      from one's family of origin in migration is perceived as problematic by both men
      and women, however, while males' distance from their kin might make them feel
      overwhelmed with family responsibilities and give way to deviant behaviors, women
      suffer from the lack of support and protection by their extended family.
      Implications for practice are also discussed.

PMID- 29358983
TI  - On Finding the Source of Human Energy: The Influence of Famous Quotations on
      Willpower.
AB  - Positive psychology focuses on aspects that human beings can improve, thereby
      enhancing their growth and happiness. One of these aspects is willpower, a
      quality that has been demonstrated to have various benefits on people, as widely
      shown in the literature. As a result, a growing body of research is attempting to
      establish the conditions under which an individual's willpower can be increased.
      This work attempts to confirm whether the famous quotations that people often use
      to inspire or motivate themselves can have a real effect on willpower. Two
      experiments were conducted assigning randomly subjects to a group and priming
      them with famous quotations, and afterwards comparing their performance in a
      willpower task with a control group. The second experiment added a willpower
      depletion task before priming. As a result, primed subjects endured the willpower
      task significantly more time than control group, demonstrating that famous
      quotations related to willpower help to increase this capacity and to counteract
      the effect of willpower depletion.

PMID- 29358984
TI  - The Influence of Planning and Response Inhibition on Cognitive Functioning of Non
      Psychotic Unipolar Depressed Suicide Attempters.
AB  - Depression is one of the main risk factors for suicide. However, little is known
      about the intricate relationships among depressive symptomatology in unipolar
      depression, suicide risk, and the characteristics of executive dysfunction in
      depressed patients. We compared 20 non-psychotic unipolar depressed suicide
      attempters to 20 matching depressed non-attempters and to 20 healthy controls to
      further investigate the possible differences in neuropsychological performance.
      Depressed subjects were controlled for current suicidal ideation, and their
      neuropsychological profile was assessed using a range of measures of executive
      functioning, attention, verbal memory, processing speed, and psychomotor speed.
      Depressed groups were outperformed by healthy controls. Depressed attempters
      presented more cognitive impairment than depressed non-attempters on a simple
      Go/No-go response inhibition task and performed better than non-attempters on the
      Tower of London planning task. Depressed attempters were clearly distinguished by
      a deficit in response inhibition (Go/No-go commission errors). The normative
      planning performance (Tower of London extra moves) of the suicide attempters was
      unexpected, and this unanticipated finding calls for further research. Normative
      planning may indicate an increased risk of suicidal behavior.

PMID- 29358985
TI  - Conceptual Referents, Personality Traits and Income-Happiness Relationship: An
      Empirical Investigation.
AB  - One of the ongoing debates in social indicator and subjective well-being research
      is concerned with the weak relationship between objective (such as income) and
      subjective indicators of well-being (such as life satisfaction). Empirical
      studies show that the relationship between subjective and the traditional
      objective well-being indicators is weak. This relationship is found to be very
      complex and far from clear. The present study tries to shed lights behind the
      complexity of the relationship between income and subjective well-being (SWB) by
      bringing into the analysis some alternative factors such as heterogeneity in the
      human perception and purpose of life (conceptual referent theory) and personality
      traits. Conceptual referent theory of happiness proposes that people differ in
      their conceptual referent for a happy life and this referent plays a significant
      role in their judgment about happiness and life satisfaction. Results of this
      cross-sectional survey based on 500 individuals residing in rural and urban areas
      indicate that the relationship between income and life satisfaction is not very
      strong. Furthermore, the relationship between income and life satisfaction is
      contingent on a person's conceptual referent for happiness. This study suggests
      that income seems to have a significant influence on life satisfaction for some
      people (especially with outer oriented referents) and insignificant influence for
      other people (especially holding inner oriented referents). Additionally,
      neuroticism personality trait was able to further explain the relationship
      between income and life satisfaction. It was observed that the individuals with
      higher level of neuroticism tend to get a lower level of satisfaction from income
      rise as compared to individuals with lower level of neuroticism.

PMID- 29358986
TI  - Cross-Cultural Variation in Political Leadership Styles.
AB  - Guided by gaps in the literature with regard to the study of politicians the aim
      of the research is to explore cross-cultural differences in political leaders'
      style. It compares the MLQ (Avolio & Bass, 2004) scores of elected political
      leaders (N = 140) in Bulgaria and the UK. The statistical exploration of the data
      relied on multivariate analyses of covariance. The findings of comparisons across
      the two groups reveal that compared to British political leaders, Bulgarian
      leaders were more likely to frequently use both transactional and
      passive/avoidant behaviours. The study tests Bass's (1997) strong assertion about
      the universality of transformational leadership. It contributes to the leadership
      literature by providing directly measured data relating to the behaviours of
      political leaders. Such information on the characteristics of politicians could
      allow for more directional hypotheses in subsequent research, exploring the
      contextual influences within transformational leadership theory. The outcomes
      might also aid applied fields. Knowledge gained of culturally different leaders
      could be welcomed by multicultural political and economic unions, wherein
      understanding and allowances might aid communication.

PMID- 29358987
TI  - The Association Between Physical Activity and Cognitive Function With
      Considerations by Social Risk Status.
AB  - We evaluated the association between physical activity and cognitive function
      among a national sample of the broader U.S. adult population, with consideration
      by social risk. Data from the 1999-2002 National Health and Nutrition Examination
      Survey (NHANES) were used to identify 2031 older adults, ages 60-85. Social risk
      was classified by measuring four NHANES variables, namely poverty level,
      education, minority status, and social living status, which were graded on a
      scale of 0-4, with higher scores corresponding with higher social risk. The Digit
      Symbol Substitution Test (DSST) was used to assess cognitive function. Physical
      activity was assessed via a validated self-report questionnaire. After
      adjustments, meeting physical activity guidelines (vs not) was associated with
      greater cognitive function (beta = 3.0, 95% CI [1.5, 4.4], p < 0.001). In this
      same model, social risk status was also independently associated with cognitive
      function. Meeting physical activity guidelines (vs. not) was not associated with
      higher cognitive function among those with a social risk score of of 3 (beta = 
      0.01; 95% CI [-6.3, 6.4], p = 0.99) or a social risk score of 4 (beta = -6.8, 95%
      CI [-15.7, 2.0], p = 0.12). In this national sample of older adults, meeting
      physical activity guidelines, and degree of social risk were independently
      associated with cognitive function. However, physical activity was not associated
      with cognitive function among older adults with the highest degree of social
      risk.

PMID- 29358988
TI  - The Sensation Seeking Scale (SSS-V) and Its Use in Latin American Adolescents:
      Alcohol Consumption Pattern as an External Criterion for Its Validation.
AB  - Sensation Seeking is a trait defined by the seeking of varied, novel, complex,
      and intense situations and experiences, and the willingness to take physical,
      social, and financial risks for the sake of such experience. The Sensation
      Seeking Scale (SSS-V) is the most widely used measure to assess this construct.
      In previous studies a variety of psychometric limitations were found when using
      the SSS-V with Latin American population. The purpose of this study is to present
      additional psychometric properties for its use with Latin American adolescents.
      It was applied to a 506 adolescent sample (from 12 to 20 years). The result is a
      scale of 22 items that cover four factors. It seems that sensation seeking among
      Latin American adolescents can be described in terms of four factors, but with
      some slightly content differences from what is usually found in adult samples
      from other countries. Future lines of research are proposed.

PMID- 29358989
TI  - Daydream Believer: Rumination, Self-Reflection and the Temporal Focus of Mind
      Wandering Content.
AB  - Current research into mind-wandering is beginning to acknowledge that this
      process is one of heterogeneity. Following on from previous findings highlighting
      the role of self-focus during mind wandering, the present study aimed to examine
      individual differences in rumination and self-reflection and the impact such
      styles of self-focus may have on mind-wandering experiences. Thirty-three
      participants were required to complete the Sustained Attention Response Task
      (SART), aimed at inducing mind-wandering episodes, whilst also probing the
      content of thought in terms of temporal focus. Self-report questionnaires were
      also administered after the SART to measure dispositional differences in style
      and beliefs regarding mind-wandering and assessments of individual differences in
      rumination and self-reflection. Those individuals with reflective self-focus
      showed a strong positive association with positive and constructive thoughts.
      Critically, ruminative self-focus was positively associated with a tendency for
      the mind to wander towards anguished fantasies, failures and aggression, but it
      was also positively associated with positive and constructive thoughts.
      Furthermore, while dispositional differences in self-focus showed no relationship
      with the temporal perspective of thoughts when probed during a cognitive task,
      performance on the task itself was related to whether participants were thinking
      about the past, present or future during that activity. Such findings are
      discussed in line with previous research, and provide a further step towards
      accounting for the heterogeneous nature of mind-wandering.

PMID- 29358990
TI  - A Window Into the Bright Side of Psychology: Interview With Mihaly
      Csikszentmihalyi.
AB  - Mihaly Csikszentmihalyi is one of the most eminent psychologists of the modern
      era. His ideas, such as flow, or the systems model of creativity, have inspired
      numerous studies, theoretical analyses as well as pedagogic and psychological
      interventions. Alongside Martin Seligman, he founded positive psychology and
      continues to work to promote it. In this interview, he shares the stories behind
      his scientific interests, sources of scientific ideas and the process of
      promoting the concepts he had written about. He also shares his thoughts about
      academic work performance.

PMID- 29358991
TI  - Management of anemia in inflammatory bowel disease: a challenge in everyday
      clinical practice.
AB  - Anemia is the most common extraintestinal manifestation and complication of
      inflammatory bowel disease (IBD). Its etiology is multifactorial and mostly is a
      combination of iron deficiency anemia (IDA) and chronic anemia (ACD). Because of
      its high incidence in patients with IBD and its influence on their quality of
      life, regular screening is recommended. In case of IDA type of medication and
      route of administration should be determined by many factors such as general
      condition of the patient, IBD activity or anemia severity. Intravenous iron
      supplementation is the preferred route but may be associated with phosphate drop
      or even severe hypophosphatemia (HP). The mechanism of HP related to the
      intravenous iron infusions is not clearly known yet, but it might be related to
      the change of FGF-23 levels. What more not all parenteral forms of iron are equal
      and some may have a higher risk of HP than others.

PMID- 29358992
TI  - The role of pH in symptomatic relief and effective treatment of gastroesophageal
      reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a condition in which gastroduodenal
      contents pass into the oesophagus and cause troublesome symptoms and
      complications. The aetiopathogenesis of gastroesophageal reflux disease is
      complex and multifactorial. Acid reflux plays an important role in the GERD
      pathogenesis, both in erosive and non-erosive reflux disease. Reduction of GERD
      symptoms and mucosal healing correlates with the number of hours that
      intragastric acid is suppressed to a pH > 4.0. Mucosal healing was achieved in
      most of patients who received different types of proton pump inhibitors, but only
      in 50% of those who received H2 blockers. These findings seem to be best
      accounted for by differences in the duration and degree of acid suppression
      achieved by different classes of drugs and perhaps between agents within those
      classes.

PMID- 29358993
TI  - Percutaneous cholecystostomy for delayed laparoscopic cholecystectomy in patients
      with acute cholecystitis: analysis of a single-centre experience and literature
      review.
AB  - Introduction: Percutaneous cholecystostomy (PC) has been used as a relatively
      safe and efficient temporising measure in the treatment of acute cholecystitis
      (AC) in high-risk patients with serious co-morbidity and in elderly patients.
      Aim: To assess the effectiveness, possible advantages, and complication of
      delayed laparoscopic cholecystectomy (LC) following PC in patients with AC.
      Material and methods: A total of 52 LC for AC were divided into two groups: the
      first group consisted of patients who had PC followed by LC (PCLC group, n = 12),
      and the second group consisted of patients who had conservative treatment
      followed by LC (non-PCLC group, n = 40). Eight of these patients were males and
      four were female. The groups were statistically compared regarding their
      demographic, comorbidity, hospital stay, conservation, and complication rates. PC
      was performed via the transhepatic route under ultrasound guidance using local
      anaesthesia. Results: Percutaneous cholecystostomy was technically successful in
      12 patients with no attributable mortality or major complications. Upon the
      regression of cholecystitis and the decrease in APACHE-II scores, the PC catheter
      was unplugged and elective LC was scheduled for after 8 weeks. Ninety-two percent
      had complete resolution of symptoms within 48 h of intervention while 8% had
      partial resolution. All of the patients in PCLC and non-PCLC groups recovered
      well from cholecystectomy. Conclusions: This study suggests that PCLC would not
      significantly improve the outcome of LC as assessed by conversion and morbidity
      rate and hospital stay compared with non-PCLC. Percutaneous cholecystostomy is a
      valid alternative for patients with acute cholecystitis. And our study shows that
      the laparoscopic cholecystectomy is a good option in high-risk patients who have
      been treated by percutaneous cholecystostomy for acute cholecystitis.

PMID- 29358994
TI  - The incidence of HLA-DQ2/DQ8 in Turkish children with celiac disease and a
      comparison of the geographical distribution of HLA-DQ.
AB  - Introduction: Celiac disease (CD) is an auto-immune enteropathy that occurs in
      genetically pre-disposed people as a result of the consumption of gluten
      containing foods. Aim: To identify the incidence of HLA-DQ2 and HLA-DQ8 observed
      in children with CD. Material and methods: In this study, we focused on children
      ranging in age from 2 to 18 years and diagnosed with celiac disease. In our
      patients diagnosed with CD, in addition to tissue transglutaminase antibodies
      (anti-tTG), we also evaluated HLA-DQ2 B1 and HLA-DQ8 B1 alleles using the method
      of polymerase chain reaction (PCR)/sequence-specific oligonucleotide probes
      (Luminex(r)). The detection of 0201/0202 for HLA-DQ2 allele and 0302 for HLA-DQ8
      allele was accepted as a positive result. Results: The mean age of our patients
      with celiac disease was 7.42 +/-3.18 years, and the female/male ratio was 1.5/1.
      Seventy-six percent of our patients were HLA-DQ2 and/or HLA-DQ8 positive, 67%
      were HLA-DQ2 positive, and 25% were HLA-DQ8 positive. Nevertheless, 24% of them
      were HLA-DQ2 and HLA-DQ8 negative. The incidence of HLA-DQ2 in the control group
      was 18.8% with a significant difference compared to the HLA-DQ2 incidence in the
      patient group (67%) (p < 0.05). Similarly the HLA-DQ8 incidence in the control
      group (5.7%) was significantly lower than the incidence in the patient group
      (25%) (p < 0.05). Conclusions: The incidence of the patients diagnosed with CD,
      who are HLA-DQ2 and HLA-DQ8 negative, varies among different populations.

PMID- 29358995
TI  - Differentially regulated ADAMTS1, 8, 9, and 18 in pancreas adenocarcinoma.
AB  - Introduction: Despite recent diagnostic and therapeutic improvements, pancreas
      cancer remains one of the highly lethal cancers. The extracellular matrix (ECM)
      is a physiological barrier that limits the spread of cancer cells into
      surrounding tissues and distant organs. Disintegrin and metalloprotease with
      thrombospondin motifs (ADAMTS) is a family of 19 proteases, which is involved in
      various biological processes such as ECM remodelling and anti-angiogenesis. Aim:
      To investigate the expression of ADAMTS1, 8, 9, and 18 proteinases in pancreas
      adenocarcinoma and its nodal metastasis. Material and methods: The immunostaining
      status of ADAMTS1, 8, 9, and 18 were investigated in formalin-fixed paraffin
      embedded samples of 25 patients who underwent pancreaticoduodenectomy for an
      adenocarcinoma located at the head of the pancreas. Results: In semi-quantitive
      grading pathologically, ADAMTS1, 8, 9, and 18 were found to be highly stained in
      all cancerous pancreas samples compared with normal pancreas. In addition, the
      immune positivity of ADAMTS1, 9, and 18 was found to be higher in metastatic
      lymph nodes than in non-metastatic lymph tissue. Tumour size was correlated with
      ADAMTS9 and 18 expressions in cancerous pancreas. Conclusions: According to the
      data obtained from the study, we suggest that these four ADAMTSs may have
      significant roles in the tumorigenesis and nodal spread of pancreas
      adenocarcinoma.

PMID- 29358996
TI  - Comparative effectiveness of aggressive intravenous fluid resuscitation with
      lactated Ringer's solution and rectal indomethacin therapy in the prevention of
      pancreatitis after endoscopic retrograde cholangiopancreatography: a double blind
      randomised controlled clinical trial.
AB  - Introduction: There is growing evidence indicating the aggressive intravenous
      fluid resuscitation (IVFR) can decrease the rate of pancreatitis; however, to the
      best of our knowledge it has not been well studied in a post-endoscopic
      retrograde cholangiopancreatography (post-ERCP) setting. Aim: To compare the
      effects of aggressive IVFR and rectal indomethacin (RI) in preventing
      pancreatitis after ERCP. Material and methods: This is a double blind randomised
      controlled clinical trial on 186 patients undergoing ERCP in Ahvaz, Iran. The
      inclusion criteria were ERCP for standard clinical indications such as
      choledocholithiasis, bile duct leak, and biliary obstruction. The IVFR group (n =
      62) received a bolus of 20 ml/kg of body weight lactated Ringer's solution (LRS)
      immediately after ERCP, followed by 3 ml/kg/h maintenance for 8 h. The RI group
      (n = 62) received 50 mg rectal indomethacin immediately before procedure and 12 h
      after ERCP. The control group (n = 62) did not receive any treatment. Results:
      Post-ERCP pancreatitis in IVFR, rectal indomethacin, and control groups occurred
      in 8 (12.9%), 16 (25.8%), and 20 (32.3%) patients (p = 0.036). Pancreatic pain
      was reported in 13 (21%), 21 (33.9%), and 27 (43.5%) patients in the IVFR, RI,
      and control group (p = 0.046). The serum amylase level increased over 24 h after
      intervention in all three groups. The mean serum amylase level 8 h after
      intervention in the IVFR patients was lower than the RI and control groups.
      Conclusions: Intravenous fluid resuscitation with LRS was more effective in
      preventing post-ERCP pancreatitis in comparison to the rectal indomethacin and
      control group.

PMID- 29358997
TI  - Characteristics and outcomes of gastroduodenal ulcer bleeding: a single-centre
      experience in Lithuania.
AB  - Introduction: Despite the optimal use of combined endoscopic haemostasis and
      pharmacologic control of acid secretion in the stomach, mortality in patients
      with peptic ulcer bleeding (PUB) has remained constant. Recent data has shown
      that the majority of patients with PUB die of non-bleeding-related causes. Aim:
      To provide an overview of our experience of PUB management, with emphasis on the
      effect of age, gender, comorbidities, and drug use on the characteristics and
      outcomes of gastroduodenal ulcer bleeding. Material and methods: We
      retrospectively reviewed the medical records of all patients admitted with the
      primary diagnosis of acute, chronic or unspecified gastric and/or duodenal ulcer
      with haemorrhage during 2008-2012. Results: Two hundred and nineteen patients
      were identified. 46.6% of patients were >= 65 years old (elderly) and 53.4% were
      < 65 years old (young). The young patients were more likely to have duodenal
      ulcers and liver failure at admission. Previous use of medications was more
      regularly observed in gastric ulcer patients than in duodenal ulcer patients.
      Rebleeding occurred in 43 (19.6%) patients and death in 5 (2.3%) patients.
      Increased risk of mortality in our patients was associated with age >= 65 years
      (RR = 2.21; 95% CI: 1.90-2.56; p = 0.021). Conclusions: Management of peptic
      ulcer bleeding should aim at reducing the risk of multiorgan failure and
      cardiopulmonary death instead of focusing merely on successful haemostasis.

PMID- 29358998
TI  - Current smoking improves ulcerative colitis patients' disease behaviour in the
      northwest of China.
AB  - Introduction: The incidence of ulcerative colitis has increased tremendously over
      the past few decades, and caused much more attention in China. Several studies
      have revealed that both environmental and genetic factors play crucial roles in
      the formation and development of this disease. Among the environmental factors,
      the smoking condition is highly significant. Although current smoking has been
      associated with a protective effect on both the development and progression of
      ulcerative colitis (UC), the clinical characteristics of UC patients with current
      smoking in China is still unclear. Aim: To clarify the relationship between
      current smoking and the UC in the northwest of China, patients diagnosed with
      ulcerative colitis in the General Hospital of Ningxia Medical University from
      2003.03 to 2012.09 were assessed. Material and methods: Data were collected about
      clinical features, cigarette smoking conditions, disease location, and
      therapeutic requirements. A total of 421 patients were included in this study, at
      diagnosis, 341 (81%) patients were non-smokers, and the current smokers amounted
      to 80 (19%). Results: As for disease location, there were no differences between
      the current smokers and non-smokers regarding proctitis and extensive colitis,
      but the current smokers had less left-sided colitis than non-smokers (p = 0.049).
      Based on the Modified Mayo score, heavier smokers had lower scores than other
      smokers and non-smokers. For the therapeutic requirements, current smokers needed
      fewer corticosteroids than non-smokers (p = 0.048). Conclusions: We found that
      current smoking is closely associated with a protective factor for UC.

PMID- 29358999
TI  - The efficacy and duration of treatment with propranolol in children with cyclic
      vomiting syndrome in southern Iran.
AB  - Introduction: Cyclic vomiting syndrome is a functional disorder characterised by
      repeated episodes of nausea and vomiting with symptom-free intervals between the
      attacks. Cyclic vomiting syndrome is a migraine equivalent; therefore, anti
      migraine medications are effective for cyclic vomiting syndrome prophylaxis, but
      duration of treatment is not clear. Aim: To determine the efficacy and duration
      of drug therapy in cyclic vomiting syndrome. Material and methods: This study was
      conducted on 206 cases of cyclic vomiting syndrome, who were treated with
      propranolol as prophylaxis. After they were symptom-free for at least 9 months,
      propranolol was tapered and discontinued and then they were followed for at least
      6 months after drug withdrawal for evaluation of recurrence. Results: The study
      subjects included 127 boys and 79 girls. The mean age of symptom onset was 3.4
      years (range: 3 months to 14.5 years) and the mean age at the time of diagnosis
      was 5.7 years (range: 8.4 months to 18 years). Among the 206 patients in whom
      propranolol was discontinued, only 16 (7.8%) subjects developed recurrence of
      symptoms in the 6-month follow-up period. Conclusions: There is no need to
      continue prophylaxis of cyclic vomiting syndrome for a long time. It is also
      possible to make the duration of drug therapy shorter, which is useful for the
      convenience of the patients and prevention of drug side effects.

PMID- 29359000
TI  - Position change during colonoscopy improves caecal intubation rate, mucosal
      visibility, and adenoma detection in patients with suboptimal caecal preparation.
AB  - Introduction: Most colonoscopies are completed in the left lateral (LL) position
      but in cases of suboptimal caecal preparation, changing the patient's position to
      supine (S) and, if needed, to right lateral (RL) improves caecal intubation rate,
      mucosal visibility, and adenoma detection. Aim: To determine if position change
      during colonoscopy facilitates optimal visualisation of the caecum. Material and
      methods: A total of 359 patients were grouped into three categories based on the
      initial caecal intubation position. After caecal intubation, caecal visibility
      was scored on a four-point scale depending on the number of imaginary quadrants
      of the caecum completely visualized - Arya Caecal Prep Score. A score of 1 or 2
      was unsatisfactory, while 3 or 4 was considered satisfactory. In patients with
      unsatisfactory score, position was changed from LL to S and then RL and
      visibility was scored again. Results: The initial caecal intubation in the LL
      position was achieved in 66.8% of patients, S in 28.5%, and RL in 4.8% of
      patients. 84.5% (300/355) of patients had an acceptable visualisation score at
      the initial caecal intubation position. Of the 55 patients with unsatisfactory
      caecum visualisation scores in the initial intubation position, 30 (8.5%) had
      satisfactory scores after the first position change (95% CI: 5.77-11.84). Twenty
      five (7.04%) subjects required two position changes (95% CI: 4.61-10.22%). An
      additional 9.3% (11/118) of adenomas were detected in caecum and ascending colon
      following position change. Conclusions: Changing patient position improves caecal
      intubation rate, mucosal visibility, and adenoma detection.

PMID- 29359001
TI  - The role of endoscopic retrograde cholangiopancreatography in choledochal cysts
      and/or abnormal pancreatobiliary junction in children.
AB  - Introduction: Biliary cysts with an abnormal pancreatobiliary junction are one of
      the most common pancreatobiliary malformations. The main symptom is cholestasis;
      endoscopic retrograde cholangiopancreatography (ERCP) plays a key role in
      diagnosis. Aim: Retrospective evaluation of ERCP performed to diagnose
      abnormalities of the pancreatobiliary junction. Material and methods: We
      retrospectively evaluated ERCP performed to diagnose abnormalities of the
      pancreatobiliary junction, mainly choledochal cysts, in 112 children between 1990
      and 2011. Results: We performed 112 examinations of 50 children with abnormal
      pancreatobiliary junction and choledochal cysts (15 males and 35 females, average
      age: 5 years, range: 1 month - 15 years). Cysts were associated with a common
      channel in 37 (74%) cases, were not associated with a common channel in 9 (18%)
      cases, and in 3 (6%) cases the common channel lacked cysts. We performed
      endoscopic papilla sphincterotomy on 33 (66%) patients; endoscopic drainage was
      performed 62 times, including 17 patients without papilla sphincterotomy. In 15
      (30%) cases, we only performed sphincterotomy. Extraction of lithiasis was done
      in 2 (4%) cases. Both ERCP and magnetic resonance cholangiopancreatography (MRCP)
      were performed on 13 patients. There was concordance of the choledochal cyst and
      of the type of cyst in both methods; however, common channels could not be
      observed by MRCP. There was 1 serious complication (perforation after
      sphincterotomy) and 11 (9%) mild adverse events. Conclusions: When performed at
      an expert centre, ECRP is a safe and reliable procedure for children with
      choledochal cysts and/or an abnormal pancreatobiliary junction. Endoscopic
      retrograde cholangiopancreatography remains a reasonable alternative because MRCP
      has a limited ability to diagnose the precise anomalies of the pancreatobiliary
      junction and has no therapeutic capabilities.

PMID- 29359002
TI  - Case of oesophageal gastrointestinal stromal tumour.

PMID- 29359003
TI  - Spontaneous bacterial peritonitis by Clostridium species and antimicrobial
      therapy.

PMID- 29359004
TI  - Giant paraesophageal hernia-related chronic gastric volvulus case to the emergent
      surgery.

PMID- 29359005
TI  - Wear Characteristic of Stellite 6 Alloy Hardfacing Layer by Plasma Arc Surfacing
      Processes.
AB  - The microstructure and wear resistance of Stellite 6 alloy hardfacing layer at
      two different temperatures (room temperature and 300 degrees C) were investigated
      by plasma arc surfacing processes on Q235 Steel. Tribological test was conducted
      to characterize the wear property. The microstructure of Stellite 6 alloy coating
      mainly consists of alpha-Co and (Cr, Fe)7C3 phases. The friction coefficient of
      Stellite 6 alloys fluctuates slightly under different loads at 300 degrees C. The
      oxide layer is formed on the coating surface and serves as a special lubricant
      during the wear test. Abrasive wear is the dominant mechanism at room
      temperature, and microploughing and plasticity are the key wear mechanisms at 300
      degrees C.

PMID- 29359007
TI  - Discovery and Biological Evaluation of Natural Phenolic Antioxidants.

PMID- 29359006
TI  - The Significance of Hypothiocyanite Production via the Pendrin/DUOX/Peroxidase
      Pathway in the Pathogenesis of Asthma.
AB  - Inhaled corticosteroids (ICSs) are used as first-line drugs for asthma, and
      various novel antiasthma drugs targeting type 2 immune mediators are now under
      development. However, molecularly targeted drugs are expensive, creating an
      economic burden on patients. We and others previously found pendrin/SLC26A4 as a
      downstream molecule of IL-13, a signature type 2 cytokine critical for asthma,
      and showed its significance in the pathogenesis of asthma using model mice.
      However, the molecular mechanism of how pendrin causes airway inflammation
      remained elusive. We have recently demonstrated that hypothiocyanite (OSCN-)
      produced by the pendrin/DUOX/peroxidase pathway has the potential to cause airway
      inflammation. Pendrin transports thiocyanate (SCN-) into pulmonary lumens at the
      apical side. Peroxidases catalyze SCN- and H2O2 generated by DUOX into OSCN-. Low
      doses of OSCN- activate NF-kappaB in airway epithelial cells, whereas OSCN- in
      high doses causes necrosis of the cells, inducing the release of IL-33 and
      accelerating inflammation. OSCN- production is augmented in asthma model mice and
      possibly in some asthma patients. Heme peroxidase inhibitors, widely used as
      antithyroid agents, diminish asthma-like phenotypes in mice, indicating the
      significance of this pathway. These findings suggest the possibility of
      repositioning antithyroid agents as antiasthma drugs.

PMID- 29359008
TI  - Salusin-beta Is Involved in Diabetes Mellitus-Induced Endothelial Dysfunction via
      Degradation of Peroxisome Proliferator-Activated Receptor Gamma.
AB  - The pathophysiological mechanisms for vascular lesions in diabetes mellitus (DM)
      are complex, among which endothelial dysfunction plays a vital role. Therapeutic
      target against endothelial injury may provide critical venues for treatment of
      diabetic vascular diseases. We recently identified that salusin-beta contributed
      to high glucose-induced endothelial cell apoptosis. However, the roles of salusin
      beta in DM-induced endothelial dysfunction remain largely elusive. Male C57BL/6J
      mice were used to induce type 2 diabetes mellitus (T2DM) model. Human umbilical
      vein endothelial cells (HUVECs) were cultured in high glucose/high fat (HG/HF)
      medium. We demonstrated increased expression of salusin-beta in diabetic aortic
      tissues and high-glucose/high-fat- (HG/HF-) incubated HUVECs. Disruption of
      salusin-beta by shRNA abrogated the reactive oxygen species (ROS) production,
      inflammation, and nitrotyrosine content of HUVECs cultured in HG/HF medium. The
      HG/HF-mediated decrease in peroxisome proliferator-activated receptor gamma
      (PPARgamma) expression was restored by salusin-beta shRNA, and PPARgamma
      inhibitor T0070907 abolished the protective actions of salusin-beta shRNA on
      endothelial injury in HG/HF-treated HUVECs. Salusin-beta silencing obviously
      improved endothelium-dependent vasorelaxation, oxidative stress, inflammatory
      response, and nitrative stress in diabetic aorta. Taken together, our results
      highlighted the essential role of salusin-beta in pathological endothelial
      dysfunction, and salusin-beta may be a promising target in treatment of vascular
      complications of DM.

PMID- 29359009
TI  - Exercise Combined with Rhodiola sacra Supplementation Improves Exercise Capacity
      and Ameliorates Exhaustive Exercise-Induced Muscle Damage through Enhancement of
      Mitochondrial Quality Control.
AB  - Mounting evidence has firmly established that increased exercise capacity (EC) is
      associated with considerable improvements in the survival of patients with
      cardiovascular disease (CVD) and that antistress capacity is a prognostic
      predictor of adverse cardiovascular events in patients with CVD. Previous studies
      have indicated that aerobic exercise (AE) and supplementation with Rhodiola sacra
      (RS), a natural plant pharmaceutical, improve EC and enable resistance to stress;
      however, the underlying mechanism remains unclear. This study explored the
      ability of AE and RS, alone or combined, to improve EC and ameliorate exhaustive
      exercise- (EE-) induced stress and elucidate the mechanism involved. We found
      that AE and RS significantly increased EC in mice and ameliorated EE-induced
      stress damage in skeletal and cardiac muscles (SCM); furthermore, a synergistic
      effect was detected for the first time. To our knowledge, the present work is the
      first to report that AE and RS activate mitophagy, mitochondrial dynamics, and
      biogenesis in SCM, both in the resting state and after EE. These data indicate
      that AE and RS synergistically improve EC in mice and protect SCM from EE-induced
      stress by enhancing mitochondrial quality control, including the activation of
      mitophagy, mitochondrial dynamics, and biogenesis, both at rest and after EE.

PMID- 29359010
TI  - Modulatory Effect of Fermented Papaya Extracts on Mammary Gland Hyperplasia
      Induced by Estrogen and Progestin in Female Rats.
AB  - Fermented papaya extracts (FPEs) are obtained by fermentation of papaya by
      Aspergillus oryzae and yeasts. In this study, we investigated the protective
      effects of FPEs on mammary gland hyperplasia induced by estrogen and progestogen.
      Rats were randomly divided into 6 groups, including a control group, an FPE-alone
      group, a model group, and three FPE treatment groups (each receiving 30, 15, or 5
      ml/kg FPEs). Severe mammary gland hyperplasia was induced upon estradiol benzoate
      and progestin administration. FPEs could improve the pathological features of the
      animal model and reduce estrogen levels in the serum. Analysis of oxidant indices
      revealed that FPEs could increase superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) activities, decrease malondialdehyde (MDA) level in the
      mammary glands and serum of the animal models, and decrease the proportion of
      cells positive for the oxidative DNA damage marker 8-oxo-dG in the mammary
      glands. Additionally, estradiol benzoate and progestin altered the levels of
      serum biochemical compounds such as aspartate transaminase (AST), total bilirubin
      (TBIL), and alanine transaminase (ALT), as well as hepatic oxidant indices such
      as SOD, GSH-Px, MDA, and 8-oxo-2'-deoxyguanosine (8-oxo-dG). These indices
      reverted to normal levels upon oral administration of a high dose of FPEs. Taken
      together, our results indicate that FPEs can protect the mammary glands and other
      visceral organs from oxidative damage.

PMID- 29359011
TI  - Solid Lipid Curcumin Particles Induce More DNA Fragmentation and Cell Death in
      Cultured Human Glioblastoma Cells than Does Natural Curcumin.
AB  - Despite recent advancements in cancer therapies, glioblastoma multiforme (GBM)
      remains largely incurable. Curcumin (Cur), a natural polyphenol, has potent
      anticancer effects against several malignancies, including metastatic brain
      tumors. However, its limited bioavailability reduces its efficiency for treating
      GBM. Recently, we have shown that solid lipid Cur particles (SLCPs) have greater
      bioavailability and brain tissue penetration. The present study compares the
      efficiency of cell death by Cur and/or SLCPs in cultured GBM cells derived from
      human (U-87MG) and mouse (GL261) tissues. Several cell viability and cell death
      assays and marker proteins (MTT assay, annexin-V staining, TUNEL staining, comet
      assay, DNA gel electrophoresis, and Western blot) were investigated following the
      treatment of Cur and/or SLCP (25 MUM) for 24-72 h. Relative to Cur, the use of
      SLCP increased cell death and DNA fragmentation, produced longer DNA tails, and
      induced more fragmented nuclear lobes. In addition, cultured GBM cells had
      increased levels of caspase-3, Bax, and p53, with decreases in Bcl2, c-Myc, and
      both total Akt, as well as phosphorylated Akt, when SLCP, rather Cur, was used.
      Our in vitro work suggests that the use of SLCP may be a promising strategy for
      reversing or preventing GBM growth, as compared to using Cur.

PMID- 29359012
TI  - Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus.
AB  - Despite surgical removal of tumors with portal vein tumor thrombus (PVTT) in
      hepatocellular carcinoma (HCC) patients, early recurrence tends to occur, and
      overall survival (OS) periods remain extremely short. The role that hepatectomy
      may play in long-term survival for HCC with PVTT has not been established. The
      operative mortality of hepatectomy for HCC with PVTT has also not been reviewed.
      Hence, we reviewed recent literature to assess these parameters. The OS of
      patients who received hepatectomy in conjunction with multidisciplinary treatment
      tended to be superior to that of patients who did not. Multidisciplinary
      treatments included the following: preoperative radiotherapy on PVTT;
      preoperative transarterial chemoembolization (TACE); subcutaneous administration
      of interferon-alpha (IFN-alpha) and intra-arterial infusion of 5-fluorouracil (5
      FU) with infusion chemotherapy in the affected hepatic artery; cisplatin,
      doxorubicin and 5-FU locally administered in the portal vein; and subcutaneous
      injection of IFN-alpha, adjuvant chemotherapy (5-FU + Adriamycin) administration
      via the portal vein with postoperative TACE, percutaneous isolated hepatic
      perfusion and hepatic artery infusion and/or portal vein chemotherapy. The
      highest reported rate of operative mortality was 9.3%. In conclusion, hepatectomy
      for patients affected by HCC with PVTT is safe, has low mortality and might
      prolong survival in conjunction with multidisciplinary treatment.

PMID- 29359014
TI  - Recent trends in liver transplantation for alcoholic liver disease in the United
      States.
AB  - AIM: To examine temporal changes in the indications for liver transplantation
      (LT) and characteristics of patients transplanted for alcoholic liver disease
      (ALD). METHODS: We performed a retrospective cohort analysis of trends in the
      indication for LT using the United Network for Organ Sharing (UNOS) database
      between 2002 and 2015. Patients were grouped by etiology of the liver disease and
      characteristics were compared using chi2 and t-tests. Time series analysis was
      used identifying any year with a significant change in the number of transplants
      per year for ALD, and before and after eras were modeled using a general linear
      model. Subgroup analysis of recipients with ALD was performed by age group,
      gender, UNOS region and etiology (alcoholic cirrhosis, alcoholic hepatitis and
      hepatitis C - alcoholic cirrhosis dual listing). RESULTS: Of 74216 liver
      transplant recipients, ALD (n = 9400, 12.7%) was the third leading indication for
      transplant after hepatitis C and hepatocellular carcinoma. Transplants for ALD,
      increased from 12.8% (553) in 2002 to 16.5% (1020) in 2015. Time series analysis
      indicated a significant increase in the number of transplants per year for ALD in
      2013 (P = 0.03). There were a stable number of transplants per year between 2002
      and 2012 (linear coefficient 3, 95%CI: -4.6, 11.2) an increase of 177 per year
      between 2013 and 2015 (95%CI: 119, 234). This increase was significant for all
      age groups except those 71-83 years old, was observed for both genders, and was
      incompletely explained by a decrease in transplants for hepatitis C and ALD dual
      listing. All UNOS regions except region 9 saw an increase in the mean number of
      transplants per year when comparing eras, and this increase was significant in
      regions 2, 3, 4, 5, 6, 8, 10 and 11. CONCLUSION: There has been a dramatic
      increase in the number of transplants for ALD starting in 2013.

PMID- 29359013
TI  - Molecular basis of hepatocellular carcinoma induced by hepatitis C virus
      infection.
AB  - Present study outlines a comprehensive view of published information about the
      underlying mechanisms operational for progression of chronic hepatitis C virus
      (HCV) infection to development of hepatocellular carcinoma (HCC). These reports
      are based on the results of animal experiments and human based studies. Although,
      the exact delineated mechanism is not yet established, there are evidences
      available to emphasize the involvement of HCV induced chronic inflammation,
      oxidative stress, insulin resistance, endoplasmic reticulum stress, hepato
      steatosis and liver fibrosis in the progression of HCV chronic disease to HCC.
      Persistent infection with replicating HCV not only initiates several liver
      alterations but also creates an environment for development of liver cancer.
      Various studies have reported that HCV acts both directly as well as indirectly
      in promoting this process. Whereas HCV related proteins, like HCV core, E1, E2,
      NS3 and NS5A, modulate signal pathways dysregulating cell cycle and cell
      metabolism, the chronic infection produces similar changes in an indirect way.
      HCV is an RNA virus and does not integrate with host genome and therefore, HCV
      induced hepatocarcinogenesis pursues a totally different mechanism causing
      imbalance between suppressors and proto-oncogenes and genomic integrity. However,
      the exact mechanism of HCC inducement still needs a full understanding of various
      steps involved in this process.

PMID- 29359015
TI  - Reverse time-dependent effect of alphafetoprotein and disease control on survival
      of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma.
AB  - AIM: To characterize the survival of cirrhotic patients with Barcelona Clinic
      Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) and to ascertain the
      factors predicting the achievement of disease control (DC). METHODS: The
      cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt
      multidisciplinary group were subjected to the investigation. Demographic,
      clinical and tumor features, along with the best tumor response and overall
      survival were recorded. RESULTS: One hundred and ten BCLC stage C patients were
      included in the analysis; the median overall survival was 13.4 mo (95%CI: 10.6
      17.0). Only alphafetoprotein (AFP) serum level > 200 ng/mL and DC could
      independently predict survival but in a time dependent manner, the former was
      significantly associated with increased risk of mortality within the first 6 mo
      of follow-up (HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter
      showed a protective effect against death after one year (HR = 0.110, 95%CI: 0.038
      0.314, P < 0.0001). Only patients showing microvascular invasion and/or
      extrahepatic spread recorded lower chances of achieving DC (OR = 0.263, 95%CI:
      0.111-0.622, P = 0.002). CONCLUSION: The BCLC stage C HCC includes a wide
      heterogeneous group of cirrhotic patients suitable for potentially curative
      treatments. The reverse and time dependent effect of AFP serum level and DC on
      patients' survival confers them as useful predictive tools for treatment
      management and clinical decisions.

PMID- 29359016
TI  - Hospital contacts with alcohol problems prior to liver cirrhosis or pancreatitis
      diagnosis.
AB  - AIM: To evaluate prior hospital contacts with alcohol problems in patients with
      alcoholic liver cirrhosis and pancreatitis. METHODS: This was a register-based
      study of all patients diagnosed with alcoholic liver cirrhosis or pancreatitis
      during 2008-2012 in Denmark. Hospital contacts with alcohol problems
      (intoxication, harmful use, or dependence) in the 10-year period preceding the
      diagnosis of alcoholic liver cirrhosis and pancreatitis were identified. RESULTS:
      In the 10 years prior to diagnosis, 40% of the 7719 alcoholic liver cirrhosis
      patients and 40% of the 1811 alcoholic pancreatitis patients had at least one
      prior hospital contact with alcohol problems. Every sixth patient (15%-16%) had
      more than five contacts. A similar pattern of prior hospital contacts was
      observed for alcoholic liver cirrhosis and pancreatitis. Around 30% were
      diagnosed with alcohol dependence and 10% with less severe alcohol diagnoses. For
      the majority, admission to somatic wards was the most common type of hospital
      care with alcohol problems. Most had their first contact with alcohol problems
      more than five years prior to diagnosis. CONCLUSION: There may be opportunities
      to reach some of the patients who later develop alcoholic liver cirrhosis or
      pancreatitis with preventive interventions in the hospital setting.

PMID- 29359017
TI  - Efficacy and safety of sofosbuvir and ledipasvir in Japanese patients aged 75
      years or over with hepatitis C genotype 1.
AB  - AIM: To evaluate the efficacy and safety of a regimen containing sofosbuvir (SOF)
      and ledipasvir (LDV) in Japanese patients aged >= 75 years with hepatitis C
      genotype 1. METHODS: This multicenter, retrospective study consisted of 246
      Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in
      Japan. Demographic, clinical, virological, and adverse effects (AE)-related data
      obtained during and after SOF/LDV therapy were collected from medical records.
      These patients were divided into two groups, younger (aged < 75 years) and
      elderly (aged >= 75 years). Virological data and AEs were analyzed by age group.
      RESULTS: The sustained virological response (SVR) rates at 12 wk after treatment
      were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75
      and >= 75 years, respectively. Common AEs during therapy were headache, pruritus,
      constipation, and insomnia. These occurred in fewer than 10% of patients, and
      their incidence was not significantly different between the younger and elderly
      groups. Two patients discontinued treatment, one due to a skin eruption and the
      other due to cerebral bleeding. CONCLUSION: Compared with younger patients,
      elderly patients had a similar virological response and tolerance to SOF/LDV
      therapy.

PMID- 29359018
TI  - Women receive more inpatient resections and ablations for hepatocellular
      carcinoma than men.
AB  - AIM: To evaluate disparities in the treatment of hepatocellular carcinoma (HCC)
      based on gender. METHODS: A retrospective database analysis using the Nationwide
      Inpatient Sample (NIS) was performed between 2010 and 2013. Adult patients with a
      primary diagnosis of hepatocellular carcinoma determined by International
      Classification of Disease 9 (ICD-9) codes were included. Univariate analysis and
      multivariate logistic regressions were performed to analyze differences in
      treatment, mortality, features of decompensation, and metastatic disease based on
      the patient's gender. RESULTS: The analysis included 62582 patients with 45908
      men and 16674 women. Women were less likely to present with decompensated liver
      disease (OR = 0.84, P < 0.001) and had less risk of inpatient mortality when
      compared to men (OR = 0.75, P < 0.001). Women were more likely to receive
      inpatient resection (OR = 1.31, P < 0.001) or an ablation (OR = 1.22, P = 0.028)
      than men. There was no significant difference between men and women in regard to
      liver transplantation and transcatheter arterial chemoembolization (TACE).
      CONCLUSION: Gender impacts treatment for hepatocellular carcinoma. Women are more
      likely to undergo an ablation or resection then men. Gender disparities in
      transplantation have resolved.

PMID- 29359019
TI  - Impact of sustained virologic response on chronic kidney disease progression in
      hepatitis C.
AB  - AIM: To determine how sustained virological response at 12 wk (SVR12) with direct
      acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection
      affects chronic kidney disease (CKD) progression. METHODS: A retrospective
      analysis was performed in patients aged >= 18 years treated for HCV with DAAs at
      the VA Greater Los Angeles Healthcare System from 2014-2016. The treatment group
      was compared to patients with HCV from 2011-2013 who did not undergo HCV
      treatment, prior to the introduction of DAAs; the control group was matched to
      the study group in terms of age, gender, and ethnicity. Analysis of variance and
      co-variance was performed to compare means between SVR12 subgroups adjusting for
      co-variates. RESULTS: Five hundred and twenty-three patients were evaluated. When
      comparing the rate of change in estimated glomerular filtration rate (eGFR) one
      year after HCV treatment to one-year before treatment, patients who achieved
      SVR12 had a decline in GFR of 3.1 mL/min +/- 0.75 mL/min per 1.73 m2 compared to
      a decline in eGFR of 11.0 mL/min +/- 2.81 mL/min per 1.73 m2 in patients who did
      not achieve SVR12 (P = 0.002). There were no significant clinical differences
      between patients who achieved SVR12 compared to those who did not in terms of
      cirrhosis, treatment course, treatment experience, CKD stage prior to treatment,
      diuretic use or other co-morbidities. The decline in eGFR in those with untreated
      HCV over 2 years was 2.8 mL/min +/- 1.0 mL/min per 1.73 m2, which was not
      significantly different from the eGFR decline noted in HCV-treated patients who
      achieved SVR12 (P = 0.43). CONCLUSION: Patients who achieve SVR12 have a lesser
      decline in renal function, but viral eradication in itself may not be associated
      improvement in renal disease progression.

PMID- 29359020
TI  - De-novo hepatocellular carcinoma after pediatric living donor liver
      transplantation.
AB  - De-novo malignancies carry an incidence ranging between 3%-26% after transplant
      and account for the second highest cause of post-transplant mortality behind
      cardiovascular disease. While the majority of de-novo malignancies after
      transplant usually consist of skin cancers, there has been an increasing rate of
      solid tumor cancers over the last 15 years. Although, recurrence of
      hepatocellular carcinoma (HCC) is well understood among patients transplanted for
      HCC, there are increasing reports of de-novo HCC in those transplanted for a non
      HCC indication. The proposed pathophysiology for these cases has been mainly
      connected to the presence of advanced graft fibrosis or cirrhosis and always
      associated with the presence of hepatitis B or C virus. We report the first known
      case of de-novo HCC in a recipient, 14 years after a pediatric living related
      donor liver transplantation for end-stage liver disease due to biliary atresia
      without the presence of hepatitis B or C virus before and after transplant. We
      present this case report to increase the awareness of this phenomenon and address
      on the utility for screening and surveillance of hepatocellular carcinoma among
      these individuals. One recommendation is to use similar guidelines for screening,
      diagnosis, and treatment for HCC as those used for primary HCC in the pre
      transplant patient, focusing on those recipients who have advanced fibrosis in
      the allograft, regardless of etiology.

PMID- 29359021
TI  - Autoimmune hepatitis in the setting of human immunodeficiency virus infection: A
      case series.
AB  - Liver injury in the setting of human immunodeficiency virus (HIV) infection is
      more commonly attributed to viral hepatitis or highly active antiretroviral
      treatment (HAART) toxicity. The severity of liver injury is an important cause of
      morbidity and mortality. The emergence of autoimmune diseases, particularly
      autoimmune hepatitis (AIH) in the setting of HIV infection, is rare. Previous
      reports indicate that elevated liver enzymes are a common denominator amongst
      these patients. We present two patients with HIV infection, on HAART, with
      virological suppression. Both patients presented with elevated liver enzymes, and
      following liver biopsies, were diagnosed with AIH. The clinical course of these
      patients underscore the therapeutic value of corticosteroids, and in some cases,
      addition of immunosuppression for AIH treatment.

PMID- 29359022
TI  - Sequential tumor-directed and lobar radioembolization before major hepatectomy
      for hepatocellular carcinoma.
AB  - Preoperative radioembolization may improve the resectability of liver tumor by
      inducing tumor shrinkage, atrophy of the embolized liver and compensatory
      hypertrophy of non-embolized liver. We describe the case of a cirrhotic Child
      Pugh A patient with a segment IV hepatocellular carcinoma requiring a left
      hepatectomy. Preoperative angiography demonstrated 2 separated left hepatic
      arteries, for segment IV and segments II-III. This anatomic variant allowed
      sequential radioembolizations, delivering high-dose 90Yttrium (160 Gy) to the
      tumor, followed 28 d later by lower dose (120 Gy) to segments II-III. After 3 mo,
      significant tumor response and atrophy of the future resected liver were
      obtained, allowing uneventful left hepatectomy. This case illustrates that, when
      anatomic disposition permits it, sequential radioembolizations, delivering
      different 90Yttrium doses to the tumor and the future resected liver, could
      represent a new strategy to prepare major hepatectomy in cirrhotic patients,
      allowing optimal tumoricidal effect while reducing the toxicity of the global
      procedure.

PMID- 29359023
TI  - Primary biliary cholangitis metachronously complicated with combined
      hepatocellular carcinoma-cholangiocellular carcinoma and hepatocellular
      carcinoma.
AB  - Primary biliary cholangitis (PBC) is a progressive cholestatic liver disease
      characterized by the presence of highly specific antimitochondrial antibodies,
      portal inflammation and lymphocyte-dominated destruction of the intrahepatic bile
      ducts, which leads to cirrhosis. While its pathogenesis remains unclear, PBC that
      shows histological progression to fibrosis carries a high risk of carcinogenesis;
      the same is true of viral liver diseases. In patients with PBC, the development
      of hepatocellular carcinoma (HCC) is rare; the development of combined
      hepatocellular carcinoma and cholangiocellular carcinoma (cHCC-CCC) is
      extraordinary. Herein, we report a rare case of PBC metachronously complicated by
      cHCC-CCC and HCC, which, to the best of our knowledge, has never been reported.
      We present a case report of a 74-year-old Japanese woman who was diagnosed as PBC
      in her 40's by using blood tests and was admitted to our department for further
      management of an asymptomatic liver mass. She had a tumor of 15 mm in size in
      segment 8 of the liver and underwent a partial resection of the liver. Subsequent
      pathological findings resulted in the diagnosis of cHCC-CCC, arising from stage 3
      PBC. One year after the initial hepatectomy, a second tumor of 10 mm in diameter
      was found in segment 5 of the liver; a partial resection of the liver was
      performed. Subsequent pathological findings led to HCC diagnosis. The component
      of HCC in the initial tumor displayed a trabecular growth pattern while the
      second HCC showed a pseudoglandular growth pattern, suggesting that metachronous
      tumors that arise from PBC are multicentric.

PMID- 29359024
TI  - Eosinophilic cholangitis treatment with budesonide.
AB  - Eosinophilic cholangitis is a rare cause of deranged obstructive liver function
      tests. It has been described as a great mimicker for malignant biliary strictures
      and bile duct obstruction. There are only case reports available on treatment
      experience for eosinophilic cholangitis. A large proportion of patients present
      with biliary strictures for which they have undergone surgery or endoscopic
      treatment and a small proportion was given systemic corticosteroid. We share our
      treatment experience using budesonide which has fewer systemic side effects to
      prednisolone and avoids invasive management.

PMID- 29359026
TI  - Short-term effects of obestatin on hexose uptake and triacylglycerol breakdown in
      human subcutaneous adipocytes.
AB  - AIM: To study complete dose-dependent effects of obestatin on lipolytic and
      glucose transport activities in human adipocyte preparations highly responsive to
      insulin. METHODS: Adipocytes were prepared by liberase digestion from
      subcutaneous abdominal adipose tissue obtained from overweight subjects
      undergoing plastic surgery. The index of lipolytic activity was the glycerol
      released in the incubation medium, while glucose transport was assessed by [3H]-2
      deoxyglucose uptake assay. RESULTS: When tested from 0.1 nmol/L to 1 MUmol/L,
      obestatin did not stimulate glycerol release; it did not inhibit the lipolytic
      effect of isoprenaline and did not alter the insulin antilipolytic effect.
      Obestatin hardly activated glucose transport at 1 MUmol/L only. Moreover, the
      obestatin stimulation effect was clearly lower than the threefold increase
      induced by insulin 100 nmol/L. CONCLUSION: Low doses of obestatin cannot directly
      influence lipolysis and glucose uptake in human fat cells.

PMID- 29359027
TI  - Heart rate is an independent predictor of all-cause mortality in individuals with
      type 2 diabetes: The diabetes heart study.
AB  - AIM: To assess the association of resting heart rate with all-cause and
      cardiovascular disease (CVD) mortality in the Diabetes Heart Study (DHS).
      METHODS: Out of a total of 1443 participants recruited into the DHS, 1315
      participants with type 2 diabetes who were free of atrial fibrillation and
      supraventricular tachycardia during the baseline exam were included in this
      analysis. Heart rate was collected from baseline resting electrocardiogram and
      mortality (all-cause and CVD) was obtained from state and national death
      registry. Kaplan-Meier (K-M) and Cox proportional hazard analyses were used to
      assess the association. RESULTS: The mean age, body mass index (BMI) and systolic
      blood pressure (SBP) of the cohort were 61.4 +/- 9.2 years, 32.0 +/- 6.6 kg/m2,
      and 139.4 +/- 19.4 mmHg respectively. Fifty-six percent were females, 85% were
      whites, 15% were blacks, 18% were smokers. The mean +/- SD heart rate was 69.8
      (11.9) beats per minute (bpm). After a median follow-up time of 8.5 years
      (maximum follow-up time is 14.0 years), 258 participants were deceased. In K-M
      analysis, participants with heart rate above the median had a significantly
      higher event rate compared with those below the median (log-rank P = 0.0223). A
      one standard deviation increase in heart rate was associated with all-cause
      mortality in unadjusted (hazard ratio 1.16, 95%CI: 1.03-1.31) and adjusted
      (hazard ratio 1.20, 95%CI: 1.05-1.37) models. Similar results were obtained with
      CVD mortality as the outcome of interest. CONCLUSION: Heart rate is an
      independent predictor of all-cause mortality in this population with type 2
      diabetes. In this study, a 1-SD increase in heart rate was associated with a 20%
      increase in risk suggesting that additional prognostic information may be gleaned
      from this ubiquitously collected vital sign.

PMID- 29359025
TI  - Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment.
AB  - Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus
      (DM) that is strongly associated with approximately five-fold increased risk of
      cardiovascular mortality. CAN manifests in a spectrum of things, ranging from
      resting tachycardia and fixed heart rate (HR) to development of "silent"
      myocardial infarction. Clinical correlates or risk markers for CAN are age, DM
      duration, glycemic control, hypertension, and dyslipidemia (DLP), development of
      other microvascular complications. Established risk factors for CAN are poor
      glycemic control in type 1 DM and a combination of hypertension, DLP, obesity,
      and unsatisfactory glycemic control in type 2 DM. Symptomatic manifestations of
      CAN include sinus tachycardia, exercise intolerance, orthostatic hypotension
      (OH), abnormal blood pressure (BP) regulation, dizziness, presyncope and syncope,
      intraoperative cardiovascular instability, asymptomatic myocardial ischemia and
      infarction. Methods of CAN assessment in clinical practice include assessment of
      symptoms and signs, cardiovascular reflex tests based on HR and BP, short-term
      electrocardiography (ECG), QT interval prolongation, HR variability (24 h,
      classic 24 h Holter ECG), ambulatory BP monitoring, HR turbulence, baroreflex
      sensitivity, muscle sympathetic nerve activity, catecholamine assessment and
      cardiovascular sympathetic tests, heart sympathetic imaging. Although it is
      common complication, the significance of CAN has not been fully appreciated and
      there are no unified treatment algorithms for today. Treatment is based on early
      diagnosis, life style changes, optimization of glycemic control and management of
      cardiovascular risk factors. Pathogenetic treatment of CAN includes: Balanced
      diet and physical activity; optimization of glycemic control; treatment of DLP;
      antioxidants, first of all alpha-lipoic acid (ALA), aldose reductase inhibitors,
      acetyl-L-carnitine; vitamins, first of all fat-soluble vitamin B1; correction of
      vascular endothelial dysfunction; prevention and treatment of thrombosis; in
      severe cases-treatment of OH. The promising methods include prescription of
      prostacyclin analogues, thromboxane A2 blockers and drugs that contribute into
      strengthening and/or normalization of Na+, K+-ATPase (phosphodiesterase
      inhibitor), ALA, dihomo-gamma-linolenic acid (DGLA), omega-3 polyunsaturated
      fatty acids (omega-3 PUFAs), and the simultaneous prescription of ALA, omega-3
      PUFAs and DGLA, but the future investigations are needed. Development of OH is
      associated with severe or advanced CAN and prescription of nonpharmacological and
      pharmacological, in the foreground midodrine and fludrocortisone acetate,
      treatment methods are necessary.

PMID- 29359028
TI  - Association of obesity with hypertension and type 2 diabetes mellitus in India: A
      meta-analysis of observational studies.
AB  - AIM: To perform a meta-analysis of the association of obesity with hypertension
      and type 2 diabetes mellitus (T2DM) in India among adults. METHODS: To conduct
      meta-analysis, we performed comprehensive, electronic literature search in the
      PubMed, CINAHL Plus, and Google Scholar. We restricted the analysis to studies
      with documentation of some measure of obesity namely; body mass index, waist-hip
      ratio, waist circumference and diagnosis of hypertension or diagnosis of T2DM. By
      obtaining summary estimates of all included studies, the meta-analysis was
      performed using both RevMan version 5 and "metan" command STATA version 11.
      Heterogeneity was measured by I2 statistic. Funnel plot analysis has been done to
      assess the study publication bias. RESULTS: Of the 956 studies screened, 18 met
      the eligibility criteria. The pooled odds ratio between obesity and hypertension
      was 3.82 (95%CI: 3.39 to 4.25). The heterogeneity around this estimate (I2
      statistic) was 0%, indicating low variability. The pooled odds ratio from the
      included studies showed a statistically significant association between obesity
      and T2DM (OR = 1.14, 95%CI: 1.04 to 1.24) with a high degree of variability.
      CONCLUSION: Despite methodological differences, obesity showed significant,
      potentially plausible association with hypertension and T2DM in studies conducted
      in India. Being a modifiable risk factor, our study informs setting policy
      priority and intervention efforts to prevent debilitating complications.

PMID- 29359029
TI  - Advances and challenges in laparoscopic surgery in the management of
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is the fifth most common malignancy and the third most
      common cause of cancer-related mortality worldwide. From the wide variety of
      treatment options, surgical resection and liver transplantation are the only
      therapeutic ones. However, due to shortage of liver grafts, surgical resection is
      the most common therapeutic modality implemented. Owing to rapid technological
      development, minimally invasive approaches have been incorporated in liver
      surgery. Liver laparoscopic resection has been evaluated in comparison to the
      open technique and has been shown to be superior because of the reported decrease
      in surgical incision length and trauma, blood loss, operating theatre time,
      postsurgical pain and complications, R0 resection, length of stay, time to
      recovery and oral intake. It has been reported that laparoscopic excision is a
      safe and feasible approach with near zero mortality and oncologic outcomes
      similar to open resection. Nevertheless, current indications include solid tumors
      in the periphery < 5 cm, especially in segments II through VI, while according to
      the consensus laparoscopic major hepatectomy should only be performed by surgeons
      with high expertise in laparoscopic and hepatobiliary surgery in tertiary
      centers. It is necessary for a surgeon to surpass the 60-cases learning curve
      observed in order to accomplish the desirable outcomes and preserve patient
      safety. In this review, our aim is to thoroughly describe the general principles
      and current status of laparoscopic liver resection for hepatocellular carcinoma,
      as well as future prospects.

PMID- 29359030
TI  - Role of oral antibiotics for prophylaxis against surgical site infections after
      elective colorectal surgery.
AB  - Over the past few decades, surgeons have made many attempts to reduce the
      incidence of surgical site infections (SSI) after elective colorectal surgery.
      Routine faecal diversion is no longer practiced in elective colonic surgery and
      mechanical bowel preparation is on the verge of being eliminated altogether.
      Intravenous antibiotics have become the standard of care as prophylaxis against
      SSI for elective colorectal operations. However, the role of oral antibiotics is
      still being debated. We review the available data evaluating the role of oral
      antibiotics as prophylaxis for SSI in colorectal surgery.

PMID- 29359032
TI  - Utility of single-incision totally extraperitoneal inguinal hernia repair with
      intraperitoneal inspection.
AB  - AIM: To study the utility of single-incision totally extraperitoneal inguinal
      hernia repair with intraperitoneal inspection. METHODS: A 2 cm transverse skin
      incision was made in the umbilicus, extending to the intraperitoneal cavity.
      Carbon dioxide was insufflated followed by insertion of laparoscope to observe
      the intraperitoneal cavity. The type of hernia was diagnosed and whether there
      was the presence of intestinal incarceration was confirmed. When an intestinal
      incarceration in the hernia sac was found, the forceps were inserted through the
      incision site and the intestine was returned to the intraperitoneal cavity
      without increasing the number of trocars. Once the peritoneum was closed, totally
      extraperitoneal inguinal hernia repair was performed, and finally,
      intraperitoneal observation was performed to reconfirm the repair. RESULTS: Of
      the 75 hernias treated, 58 were on one side, 17 were on both sides, and 10 were
      recurrences. The respective median operation times for these 3 groups of patients
      were 100 min (range, 66 to 168), 136 min (range, 114 to 165), and 125 min (range,
      108 to 156), with median bleeding amounts of 5 g (range, 1 to 26), 3 g (range, 1
      to 52), and 5 g (range, 1 to 26), respectively. Intraperitoneal observation
      showed hernia on the opposite side in 2 cases, intestinal incarceration in 3
      cases, omental adhesion into the hernia sac in 2 cases, severe postoperative
      intraperitoneal adhesions in 2 cases, and bladder protrusion in 1 case. There was
      only 1 case of recurrence. CONCLUSION: Single-incision totally extraperitoneal
      inguinal hernia repair with intraperitoneal inspection makes hernia repairs safer
      and reducing postoperative complications. The technique also has excellent
      cosmetic outcomes.

PMID- 29359031
TI  - Hepatocellular carcinoma with child Pugh-A Cirrhosis treated with stereotactic
      body radiotherapy.
AB  - AIM: To evaluate the control, survival, and hepatic function for Child Pugh (CP)
      A patients after Stereotactic body radiotherapy (SBRT) in hepatocellular
      carcinoma (HCC). METHODS: From 2009 to 2016, 40 patients with Barcelona Liver
      Clinic (BCLC) stages 0-B HCC and CP-A cirrhosis completed liver SBRT. The mean
      prescription dose was 45 Gy (40 to 50 Gy in 4-5 fractions). Local relapse,
      defined as recurrence within the planning target volume was assessed with
      intravenous multiphase contrast computed tomography or magnetic resonance imaging
      every 4-6 mo after completion of SBRT. Progression of cirrhosis was evaluated by
      CP and Model for End Stage Liver Disease scores every 3-4 mo. Toxicities were
      graded per the Common Terminology Criteria for Adverse Events (v4.03). Median
      follow-up was 24 mo. RESULTS: Forty-nine HCC lesions among 40 patients were
      analyzed in this IRB approved retrospective study. Median tumor diameter was 3.5
      cm (1.5-8.9 cm). Six patients with tumors >= 5 cm completed planned selected
      transarterial chemoembolization (TACE) in combination with SBRT. Eight patients
      underwent orthotropic live transplant (OLT) with SBRT as a bridging treatment
      (median time to transplant was 12 mo, range 5 to 23 mo). The Pathologic complete
      response (PCR) rate in this group was 62.5%. The 2-year in-field local control
      was 98% (1 failure). Intrahepatic control was 82% and 62% at 1 and 2 years,
      respectively. Overall survival (OS) was 92% and 60% at 1 and 2 years, with a
      median survival of 41 mo per Kaplan Meier analysis. At 1 and 2 years, 71% and 61%
      of patients retained CPA status. Of the patients with intrahepatic failures, 58%
      developed progressive cirrhosis, compared to 27% with controlled disease (P =
      0.06). Survival specific to hepatic failure was 92%, 81%, and 69% at 12, 18, and
      24 mo. There was no grade 3 or higher toxicity. On univariate analysis, gross
      tumor volume (GTV) < 23 cc was associated with freedom from CP progression (P =
      0.05), hepatic failure-specific survival (P = 0.02), and trended with OS (P =
      0.10). CONCLUSION: SBRT is safe and effective in HCC with early cirrhosis and may
      extend waiting time for transplant in patients who may not otherwise be immediate
      candidates.

PMID- 29359033
TI  - Risk factors for pancreatic fistula following pancreaticoduodenectomy: A
      retrospective study in a Thai tertiary center.
AB  - AIM: To analyze the risk factors of postoperative pancreatic fistula following
      pancreaticoduodenectomy in a Thai tertiary care center. METHODS: We
      retrospectively analyzed 179 patients who underwent pancreaticoduodenectomy at
      our hospital from January 2001 to December 2016. Pancreatic fistula were
      classified into three categories according to a definition made by an
      International Study Group on Pancreatic Fistula. The risk factors for pancreatic
      fistula were analyzed by univariate analysis and multivariate logistic regression
      analysis. RESULTS: Pancreatic fistula were detected in 88/179 patients (49%) who
      underwent pancreaticoduodenectomy. Fifty-eight pancreatic fistula (65.9%) were
      grade A, 22 cases (25.0%) were grade B and eight cases (9.1%) were grade C.
      Clinically relevant pancreatic fistula were detected in 30/179 patients (16.7%).
      The 30-d mortality rate was 1.67% (3/179 patients). Multivariate logistic
      regression analysis revealed that soft pancreatic texture (odds ratio = 3.598,
      95%CI: 1.77-7.32) was the most significant risk factor for pancreatic fistula. A
      preoperative serum bilirubin level of > 3 mg/dL was the most significant risk
      factor for clinically relevant pancreatic fistula according to univariate and
      multivariate analysis. CONCLUSION: Soft pancreatic tissue is the most significant
      risk factor for postoperative pancreatic fistula. A high preoperative serum
      bilirubin level (> 3 mg/dL) is the most significant risk factor for clinically
      relevant pancreatic fistula.

PMID- 29359034
TI  - Surgically treated diaphragmatic perforation after radiofrequency ablation for
      hepatocellular carcinoma.
AB  - We review 6 cases of diaphragmatic perforation, with and without herniation,
      treated in our institution. All patients with diaphragmatic perforation underwent
      radiofrequency ablation (RFA) treatments for hepatocellular carcinoma (HCC)
      performed at Kurume University Hospital and Tobata Kyoritsu Hospital. We
      investigated the clinical profiles of the 6 patients between January 2003 and
      December 2013. We further describe the clinical presentation, diagnosis, and
      treatment of diaphragmatic perforation. The change in the volume of liver and the
      change in the Child-Pugh score from just after the RFA to the onset of
      perforation was evaluated using a paired t-test. At the time of perforation, 4
      patients had herniation of the viscera, while the other 2 patients had no
      herniation. The majority of ablated tumors were located adjacent to the
      diaphragm, in segments 4, 6, and 8. The average interval from RFA to the onset of
      perforation was 12.8 mo (range, 6-21 mo). The median Child-Pugh score at the
      onset of perforation (8.2) was significantly higher compared to the median Child
      Pugh score just after RFA (6.5) (P = 0.031). All patients underwent laparotomy
      and direct suture of the diaphragm defect, with uneventful post-surgical
      recovery. Diaphragmatic perforation after RFA is not a matter that can be
      ignored. Clinicians should carefully address this complication by performing RFA
      for HCC adjacent to diaphragm.

PMID- 29359035
TI  - Ectopic gastrointestinal variceal bleeding with portal hypertension.
AB  - Massive gastrointestinal bleeding from gastrointestinal varices is one of the
      most serious complications in patients with portal hypertension. However, if no
      bleeding point can be detected by endoscopy in the predilection sites of
      gastrointestinal varices, such as the esophagus and stomach, ectopic
      gastrointestinal variceal bleeding should be considered as a differential
      diagnosis. Herein, we report a case of ectopic ileal variceal bleeding in a 57
      year-old woman, which was successfully diagnosed by multi-detector row CT (MDCT)
      and angiography and treated by segmental ileum resection. To date, there have
      been no consensus for the treatment of ectopic ileal variceal bleeding. This
      review was designed to clarify the clinical characteristics of patients with
      ectopic ileal variceal and discuss possible treatment strategies. From the PubMed
      database and our own database, we reviewed 21 consecutive cases of ileal variceal
      bleeding diagnosed from 1982 to 2017. MDCT and angiography is useful for the
      rapid examination and surgical resection of an affected lesion and is a safe and
      effective treatment strategy to avoid further bleeding.

PMID- 29359036
TI  - Selective release of circRNAs in platelet-derived extracellular vesicles.
AB  - Circular RNAs (circRNAs) are a novel class of noncoding RNAs present in all
      eukaryotic cells investigated so far and generated by a special mode of
      alternative splicing of pre-mRNAs. Thereby, single exons, or multiple adjacent
      and spliced exons, are released in a circular form. CircRNAs are cell-type
      specifically expressed, are unusually stable, and can be found in various body
      fluids such as blood and saliva. Here we analysed circRNAs and the corresponding
      linear splice isoforms from human platelets, where circRNAs are particularly
      abundant, compared with other hematopoietic cell types. In addition, we isolated
      extracellular vesicles from purified and in vitro activated human platelets,
      using density-gradient centrifugation, followed by RNA-seq analysis for circRNA
      detection. We could demonstrate that circRNAs are packaged and released within
      both types of vesicles (microvesicles and exosomes) derived from platelets.
      Interestingly, we observed a selective release of circRNAs into the vesicles,
      suggesting a specific sorting mechanism. In sum, circRNAs represent yet another
      class of extracellular RNAs that circulate in the body and may be involved in
      signalling pathways. Since platelets are essential for central physiological
      processes such as haemostasis, wound healing, inflammation and cancer metastasis,
      these findings should greatly extend the potential of circRNAs as prognostic and
      diagnostic biomarkers.

PMID- 29359037
TI  - A Predictive Model to Classify Undifferentiated Fever Cases Based on Twenty-Four
      Hour Continuous Tympanic Temperature Recording.
AB  - Diagnosis of undifferentiated fever is a major challenging task to the physician
      which often remains undiagnosed and delays the treatment. The aim of the study
      was to record and analyze a 24-hour continuous tympanic temperature and evaluate
      its utility in the diagnosis of undifferentiated fevers. This was an
      observational study conducted in the Kasturba Medical College and Hospitals,
      Mangaluru, India. A total of ninety-six (n = 96) patients were presented with
      undifferentiated fever. Their tympanic temperature was recorded continuously for
      24 hours. Temperature data were preprocessed and various signal characteristic
      features were extracted and trained in classification machine learning algorithms
      using MATLAB software. The quadratic support vector machine algorithm yielded an
      overall accuracy of 71.9% in differentiating the fevers into four major
      categories, namely, tuberculosis, intracellular bacterial infections, dengue
      fever, and noninfectious diseases. The area under ROC curve for tuberculosis,
      intracellular bacterial infections, dengue fever, and noninfectious diseases was
      found to be 0.961, 0.801, 0.815, and 0.818, respectively. Good agreement was
      observed [kappa = 0.618 (p < 0.001, 95% CI (0.498-0.737))] between the actual
      diagnosis of cases and the quadratic support vector machine learning algorithm.
      The 24-hour continuous tympanic temperature recording with supervised machine
      learning algorithm appears to be a promising noninvasive and reliable diagnostic
      tool.

PMID- 29359038
TI  - Efficient Active Sensing with Categorized Further Explorations for a Home
      Behavior-Monitoring Robot.
AB  - Mobile robotics is a potential solution to home behavior monitoring for the
      elderly. For a mobile robot in the real world, there are several types of
      uncertainties for its perceptions, such as the ambiguity between a target object
      and the surrounding objects and occlusions by furniture. The problem could be
      more serious for a home behavior-monitoring system, which aims to accurately
      recognize the activity of a target person, in spite of these uncertainties. It
      detects irregularities and categorizes situations requiring further explorations,
      which strategically maximize the information needed for activity recognition
      while minimizing the costs. Two schemes of active sensing, based on two
      irregularity detections, namely, heuristic-based and template-matching-based
      irregularity detections, were implemented and examined for body contour-based
      activity recognition. Their time cost and accuracy in activity recognition were
      evaluated through experiments in both a controlled scenario and a home living
      scenario. Experiment results showed that the categorized further explorations
      guided the robot system to sense the target person actively. As a result, with
      the proposed approach, the robot system has achieved higher accuracy of activity
      recognition.

PMID- 29359039
TI  - Regulation of Reentrainment Function Is Dependent on a Certain Minimal Number of
      Intact Functional ipRGCs in rd Mice.
AB  - Purpose: To investigate the effect of partial ablation of melanopsin-containing
      retinal ganglion cells (mcRGCs) on nonimage-forming (NIF) visual functions in rd
      mice lacking rods. Methods: The rd mice were intravitreally injected with
      different doses (100 ng/MUl, 200 ng/MUl, and 400 ng/MUl) of immunotoxin
      melanopsin-SAP. And then, the density of ipRGCs was examined. After establishing
      the animal models with different degrees of ipRGC damage, a wheel-running system
      was used to evaluate their reentrainment response. Results: Intravitreal
      injection of melanopsin-SAP led to partial ablation of ipRGCs in a dose-dependent
      manner. The survival rates of ipRGCs in the 100 ng/MUl, 200 ng/MUl, and 400
      ng/MUl groups were 74.14% +/- 4.15%, 39.25% +/- 2.29%, and 38.38% +/- 3.74%,
      respectively. The wheel-running experiments showed that more severe ipRGC loss
      was associated with a longer time needed for reentrainment. When the light/dark
      cycle was delayed by 8 h, the rd mice in the PBS control group took 4.67 +/- 0.79
      days to complete the synchronization with the shifted cycle, while those in the
      100 ng/MUl and 200 ng/MUl groups required 7.90 +/- 0.55 days and 11.00 +/- 0.79
      days to complete the synchronization with the new light/dark cycle, respectively.
      Conclusion: Our study indicates that the regulation of some NIF visual functions
      is dependent on a certain minimal number of intact functional ipRGCs.

PMID- 29359040
TI  - Characteristics of Inpatient Hypertension Cases and Factors Associated with
      Admission Outcomes in Ashanti Region, Ghana: An Analytic Cross-Sectional Study.
AB  - Background: Hypertension remains a cause of morbidity and mortality in the
      Ashanti Region of Ghana. It has been featured in the top ten causes of OPD
      attendance, admissions, and deaths since 2012. We investigated the
      sociodemographic characteristics and spatial distribution of inpatient
      hypertensives and factors associated with their admission outcomes. Methods: A
      2014 line list of 1715 inpatient HPT cases aged >=25 years was used for the cross
      sectional analytic study. Accounting for clustering, all analyses were performed
      using the "svy" command in Stata. Frequencies, Chi-square test, and logistic
      regression analysis were used in the analysis. Arc view Geographic Information
      System (ArcGIS) was used to map the density of cases by place of residence and
      reporting hospital. Results: Mean age of cases was 58 (S.D 0.0068). Females
      constituted 67.6% of the cases. Age, gender, and NHIS status were significantly
      associated with admission outcomes. Cases were clustered in the regional capital
      and bordering districts. However, low case densities were recorded in the latter.
      Conclusion: Increasing NHIS access can potentially impact positively on
      hypertension admission outcomes. Health educational campaigns targeting men are
      recommended to address hypertension-related issues.

PMID- 29359041
TI  - The Importance of Surface-Binding Site towards Starch-Adsorptivity Level in alpha
      Amylase: A Review on Structural Point of View.
AB  - Starch is a polymeric carbohydrate composed of glucose. As a source of energy,
      starch can be degraded by various amylolytic enzymes, including alpha-amylase. In
      a large-scale industry, starch processing cost is still expensive due to the
      requirement of high temperature during the gelatinization step. Therefore, alpha
      amylase with raw starch digesting ability could decrease the energy cost by
      avoiding the high gelatinization temperature. It is known that the carbohydrate
      binding module (CBM) and the surface-binding site (SBS) of alpha-amylase could
      facilitate the substrate binding to the enzyme's active site to enhance the
      starch digestion. These sites are a noncatalytic module, which could interact
      with a lengthy substrate such as insoluble starch. The major interaction between
      these sites and the substrate is the CH/pi-stacking interaction with the glucose
      ring. Several mutation studies on the Halothermothrix orenii, SusG Bacteroides
      thetaiotamicron, Barley, Aspergillus niger, and Saccharomycopsis fibuligera alpha
      amylases have revealed that the stacking interaction through the aromatic
      residues at the SBS is essential to the starch adsorption. In this review, the
      SBS in various alpha-amylases is also presented. Therefore, based on the
      structural point of view, SBS is suggested as an essential site in alpha-amylase
      to increase its catalytic activity, especially towards the insoluble starch.

PMID- 29359042
TI  - Work Interruption Experienced by Nurses during Medication Administration Process
      and Associated Factors, Northwest Ethiopia.
AB  - Background: During medication administration process, including preparation,
      administration, and documentation, there is high proportion of work interruption
      that results in medication administration errors that consequently affect the
      safety of patients. Thus, the main purpose of this study was to assess the
      prevalence of work interruption and associated factors during medication
      administration process. Methods: A prospective, observation-based, cross
      sectional study was conducted on 278 nurses. Structure observational sheet was
      utilized to collect data. EPI Info version 3.5.3 and SPSS version 20 software
      were utilized for data entry and analysis, respectively. Binary and multivariable
      logistic regression were fitted to identify the associated factors using an odds
      ratio and 95% CI. Results: The incidence of work interruption was found to be
      1,152 during medication administration process. Of this, 579 (50.3%) were
      major/severe work interruptions. Unit of work, day of the week, professional
      experience, perceived severity of work interruption, source/initiator of
      interruption, and secondary tasks were factors significantly associated with
      major work interruptions at p < 0.05. Conclusion: In this study, more than half
      of work interruption was major/severe. Thus, the authors suggest raising the
      awareness of nurses regarding the severity of work interruptions, with special
      attention to those who have lower work experience, sources of interruption, and
      secondary tasks by assigning additional nurses who manage secondary tasks and
      supportive supervision.

PMID- 29359043
TI  - TB Risk Perceptions among Medical Residents at a Tertiary Care Center in India.
AB  - Setting: Government tertiary health care center in India. Objective: To
      understand the perceptions of medical residents about their risk of developing TB
      in the workplace. Design: Cross-sectional study in which a semistructured
      questionnaire which included an open-ended question to assess their main concerns
      regarding TB in workplace was used to collect data. Results: Out of 305 resident
      doctors approached, 263 (94%) completed a structured questionnaire and 200 of
      these responded to an open-ended question. Daily exposure to TB was reported by
      141 (64%) residents, 13 (5%) reported a prior history of TB, and 175 (69%)
      respondents were aware of TB infection control guidelines. A majority reported
      concerns about acquiring TB (78%) and drug-resistant TB (88%). The key themes
      identified were concerns about developing drug-resistant TB (n = 100; 50%);
      disease and its clinical consequences (n = 39; 20%); social and professional
      consequences (n = 37; 19%); exposure to TB patients (n = 32; 16%); poor infection
      control measures (n = 27; 14%); and high workload and its health consequences (n
      = 16; 8%). Conclusion: Though many resident doctors were aware of TB infection
      control guidelines, only few expressed concern about lack of TB infection control
      measures. Doctors need to be convinced of the importance of these measures which
      should be implemented urgently.

PMID- 29359044
TI  - Postherpetic Neuralgia and Trigeminal Neuralgia.
AB  - Postherpetic neuralgia (PHN) is an unpredictable complication of varicella zoster
      virus- (VZV-) induced herpes zoster (HZ) which often occurs in elderly and
      immunocompromised persons and which can induce psychosocial dysfunction and can
      negatively impact on quality of life. Preventive options for PHN include
      vaccination of high-risk persons against HZ, early use of antiviral agents, and
      robust management of pain during the early stage of acute herpes zoster. If it
      does occur, PHN may persist for months or even years after resolution of the HZ
      mucocutaneous eruptions, and treatment is often only partially effective.
      Classical trigeminal neuralgia is a severe orofacial neuropathic pain condition
      characterized by unilateral, brief but recurrent, lancinating paroxysmal pain
      confined to the distribution of one or more of the branches of the trigeminal
      nerve. It may be idiopathic or causally associated with vascular compression of
      the trigeminal nerve root. The anticonvulsive agents, carbamazepine or
      oxcarbazepine, constitute the first-line treatment. Microvascular decompression
      or ablative procedures should be considered when pharmacotherapy is ineffective
      or intolerable. The aim of this short review is briefly to discuss the
      etiopathogenesis, clinical features, and treatment of PHN and classical
      trigeminal neuralgia.

PMID- 29359046
TI  - Clinical Factors Predictive for Intracranial Hemorrhage in Mild Head Injury.
AB  - Patients with mild head injuries, a GCS of 13-15, are at risk for intracranial
      hemorrhage. Clinical decision is needed to weigh between risks of intracranial
      hemorrhage and costs of the CT scan of the brain particularly those who are
      equivocal. This study aimed to find predictors for intracranial hemorrhage in
      patients with mild head injuries with a moderate risk of intracranial hemorrhage.
      We defined moderate risk of mild head injury as a GCS score of 13-15 accompanied
      by at least one symptom such as headache, vomiting, or amnesia or with alcohol
      intoxication. There were 153 patients who met the study criteria. Eighteen of the
      patients (11.76%) had intracranial hemorrhage. There were four independent
      factors associated with intracranial hemorrhage: history of hypertension,
      headache, loss of consciousness, and baseline GCS. The sensitivity for the
      presence of intracranial hemorrhage was 100% with the cutoff point for the GCS of
      13. In conclusion, the independent factors associated with intracranial
      hemorrhage in patients with mild head injury who were determined to be at
      moderate risk for the condition included history of hypertension, headache, loss
      of consciousness, and baseline GCS score.

PMID- 29359045
TI  - Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation.
AB  - Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a
      significant impact on men and women of reproductive and nonreproductive age, with
      a considerable burden on overall quality of life (QoL) and on psychological,
      functional, and behavioural status. Moreover, diagnostic and therapeutic
      difficulties are remarkable features in many patients. Therefore evaluation,
      assessment and objectivation tools are often necessary to properly address each
      patient and consequently his/her clinical needs. Here we review the different
      tools for pain assessment, evaluation, and objectivation; specific features
      regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with
      neuroimaging investigations will be reviewed as they provide new insights into
      CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and
      objectivation.

PMID- 29359047
TI  - Knee Fat Pad Volumes in Patients with Hemophilia and Their Relationship with
      Osteoarthritis.
AB  - Hemophilic arthropathy is a progressive, disabling condition with poorly
      understood pathobiology. Since there is an emerging interest to study the role of
      intra-articular fat pad size and biology in arthritic conditions, we explored fat
      pad volume changes in hemophilic arthropathy and to what extent they differed
      from osteoarthritis. We matched a cohort of 13 adult patients with hemophilic
      arthropathy of the knee with age- and gender-matched cohorts without
      osteoarthritis ("control cohort") and with the same degree of radiographic
      osteoarthritis ("OA cohort") in 1 : 2 fashion. Infrapatellar fat pad (IPFP) and
      suprapatellar fat pad (SPFP) volumes were calculated based on magnetic resonance
      imaging and differences in fat pad volumes, demographics, height, weight, and
      osteoarthritis scores were evaluated. Fat pad volumes were positively associated
      with body size parameters in all three cohorts but were unaffected by the degree
      of osteoarthritis. While IPFP volumes did not differ between cohorts, SPFP
      volumes expanded disproportionally with weight in hemophilia patients. Our
      observations indicate that IPFPs and SPFPs behave biologically differently in
      response to different arthritic stimuli. The exaggerated expansion of the SPFP in
      hemophilia patients highlights the importance of further studying the
      implications of fat pad biology for progression of hemophilic arthropathy.

PMID- 29359048
TI  - Experience of Facility Based Childbirth in Rural Ethiopia: An Exploratory Study
      of Women's Perspective.
AB  - Background: In Ethiopia, majority (62%) of pregnant women attend antenatal care
      at least once, yet only 26% deliver with skilled birth attendants in the
      available health units. Thus, this study explored beliefs and behaviors related
      to labour and skilled attendance among the women, their perspectives on health
      care providers, and traditional birth attendants. Methods: Sixteen key informant
      interviews and eight focus group discussions were conducted among purposively
      selected women who had previous experience of facility based childbirth but gave
      birth to their most recent child without skilled attendance in the last 12
      months. Thematic content analysis was used to elicit and assess the various
      perspectives of each group of participants interviewed. Findings: The study
      participants described a range of experiences they had during childbirth at
      health facilities that forced them to choose home delivery in their most recent
      delivery. Three themes and six subthemes emerging from women's description were
      abusive and disrespectful treatment, unskilled care, poor client provider
      interaction, noncontinuous care, lack of privacy, and traditional practices.
      Conclusion: The abuse and disrespect from providers are deterring women from
      seeking skilled attendance at birth. Thus the health care providers need to
      improve client provider relationships.

PMID- 29359049
TI  - Efficacy of Abiraterone and Enzalutamide in Pre- and Postdocetaxel Castration
      Resistant Prostate Cancer: A Trial-Level Meta-Analysis.
AB  - We examined the comparative efficacies of first-line abiraterone and enzalutamide
      in pre- and postdocetaxel settings in castration-resistant prostate cancer (CRPC)
      through a trial level meta-analysis. A mixed method approach was applied to 19
      unique studies containing 17 median overall survival (OS) estimates and 13 median
      radiographic progression-free survival (PFS) estimates. We employed a random
      effects meta-analysis to compare efficacies of abiraterone and enzalutamide with
      respect to OS and PFS. In the predocetaxel setting, enzalutamide use was
      associated with an increase in median OS of 5.9 months (p < 0.001), hazard ratio
      (HR) = 0.81, and an increase in median PFS of 8.3 months (p < 0.001), HR = 0.47
      compared to abiraterone. The advantage of enzalutamide improved after adjusting
      for baseline Gleason score to 19.5 months (p < 0.001) and 14.6 months (p < 0.001)
      in median OS and PFS, respectively. In the postdocetaxel setting, the advantage
      of enzalutamide use was nominally significant for median PFS (1.2 months p = 0.02
      without adjustment and 2.2 months and p = 0.0007 after adjustment); there was no
      significant difference in median OS between the two agents. The results from this
      comprehensive meta-analysis suggest a survival advantage with the use of first
      line enzalutamide over abiraterone in CRPC and highlight the need for prospective
      clinical trials.

PMID- 29359050
TI  - Sustained Activity of Metabotropic Glutamate Receptor: Homer, Arrestin, and
      Beyond.
AB  - When activated, metabotropic glutamate receptors (mGlus) exert long-lasting
      changes within the glutamatergic synapses. One mechanism is a tonic effect of
      downstream signal transduction pathways via sustained activation of mGlu itself.
      Like many other G protein-coupled receptors (GPCRs), mGlu can exist in a
      constitutively active state, which persists agonist independently. In this paper,
      we review the current knowledge of the mechanisms underlying the constitutive
      activity of group I mGlus. The issues concerning Homer1a mechanism in the
      constitutive activity of group I mGlus and recent findings regarding the
      significant role of beta-arrestin in sustained GPCR activity are also discussed.
      We propose that once in a state of sustained activation, the mGlu persistently
      activates downstream signaling pathways, including various adaptor proteins and
      kinases, such as beta-arrestin and mitogen-activated protein kinases. In turn,
      these effector molecules bind to or phosphorylate the mGlu C-terminal binding
      domains and consequently regulate the activation state of the mGlu.

PMID- 29359052
TI  - Anticoagulation for the Pregnant Patient with a Mechanical Heart Valve, No
      Perfect Therapy: Review of Guidelines for Anticoagulation in the Pregnant
      Patient.
AB  - Heart valve replacement with a mechanical valve requires lifelong
      anticoagulation. Guidelines currently recommend using a vitamin K antagonist
      (VKA) such as warfarin. Given the teratogenic effects of VKAs, it is often
      favorable to switch to heparin-derived therapies in pregnant patients since they
      do not cross the placenta. However, these therapies are known to be less
      effective anticoagulants subjecting the pregnant patient to a higher chance of a
      thrombotic event. Guidelines currently recommend pregnant women requiring more
      than 5 mg a day of warfarin be switched to alternative therapy during the first
      trimester. This case report highlights a patient who was switched to alternative
      therapy during her first pregnancy and suffered a devastating cerebrovascular
      accident (CVA). Further complicating her situation was during a subsequent
      pregnancy; this patient continued warfarin use during the first trimester and
      experienced multiple transient ischemic attacks (TIAs). This case highlights the
      increased risk of thrombotic events in pregnant patients with mechanical valves.
      It also highlights the difficulty of providing appropriate anticoagulation for
      the pregnant patient who has experienced thrombotic events on multiple
      anticoagulants.

PMID- 29359053
TI  - Diagnosis and Treatment of Esophageal Granular Cell Tumor: A Case Report and
      Review of the Literature.
AB  - Gastrointestinal granular cell tumors are uncommon. The most common site of
      gastrointestinal granular cell tumor (GCT) is esophagus. We report a case of
      esophageal GCT incidentally diagnosed by endoscopy. The lesion was evaluated by
      endoscopic ultrasonography and resected using the endoscopic technique without
      complication.

PMID- 29359051
TI  - Neural Mechanisms of Circadian Regulation of Natural and Drug Reward.
AB  - Circadian rhythms are endogenously generated near 24-hour variations of
      physiological and behavioral functions. In humans, disruptions to the circadian
      system are associated with negative health outcomes, including metabolic, immune,
      and psychiatric diseases, such as addiction. Animal models suggest bidirectional
      relationships between the circadian system and drugs of abuse, whereby
      desynchrony, misalignment, or disruption may promote vulnerability to drug use
      and the transition to addiction, while exposure to drugs of abuse may entrain,
      disrupt, or perturb the circadian timing system. Recent evidence suggests natural
      (i.e., food) and drug rewards may influence overlapping neural circuitry, and the
      circadian system may modulate the physiological and behavioral responses to these
      stimuli. Environmental disruptions, such as shifting schedules or shorter/longer
      days, influence food and drug intake, and certain mutations of circadian genes
      that control cellular rhythms are associated with altered behavioral reward. We
      highlight the more recent findings associating circadian rhythms to reward
      function, linking environmental and genetic evidence to natural and drug reward
      and related neural circuitry.

PMID- 29359054
TI  - A Case of Bacteremia and Meningitis Associated with Piperacillin-Tazobactam
      Nonsusceptible, Ceftriaxone Susceptible Escherichia coli during Strongyloides
      Hyperinfection in an Immunocompromised Host.
AB  - Strongyloidiasis is an emerging parasitic infection with intriguing epidemiology,
      presentation, and clinical management. We report a case of hyperinfection
      syndrome complicated by E. coli bacteremia and meningitis with one of the
      isolates showing a unique resistance pattern recently being recognized. This
      report describes the aspect of invasive bacterial infections in strongyloidiasis
      and highlights the unique susceptibility pattern of the E. coli isolate and the
      extreme caution required during the antibiotic therapy.

PMID- 29359055
TI  - Bilateral Testicular Infarction from IgA Vasculitis of the Spermatic Cords.
AB  - A 51-year-old man with type 2 diabetes mellitus and chronic obstructive pulmonary
      disease presented to the emergency room with increasing bilateral leg pain, rash,
      and scrotal swelling with pain. Skin biopsy from his thigh revealed IgA
      associated vasculitis. Due to hematuria, a renal biopsy was performed and showed
      an IgA glomerulonephritis with focal fibrinoid necrosis and neutrophil
      accumulation. Bilateral orchiectomies were performed in two separate procedures
      ten and thirteen days after the renal biopsy, as a result of uncontrolled abscess
      formation in testicles. Microscopically, both testicles revealed large abscess
      formation destroying almost the entire testicular parenchyma without tumor cells.
      Spermatic cord margins were further scrutinized microscopically to show bilateral
      vasculitis in many small size vessels, confirmed by positive endothelial staining
      for IgA. Some of the affected arteries revealed central organizing thrombi with
      recanalization features, highly suggestive of vasculitis-associated thrombi
      formation, resulting in testicular ischemic infarction and abscess formation. We
      conclude that this adult patient developed a severe form of Henoch-Schonlein
      purpura, with vasculitis affecting multiple organs, including the most serious
      and unusual complication of bilateral testicular infarction.

PMID- 29359056
TI  - Skin Hyperpigmentation as the Presenting Symptom of Subacute Combined
      Degeneration of the Spinal Cord.
AB  - Vitamin B12 deficiency results in hematological, neurological, and rarely
      dermatological complications. Subacute combined degeneration of the cord is one
      of the neurological complications, and usually the presenting symptom is
      paresthesia. Herein, we report a case of a 46-year-old man with subacute combined
      degeneration presenting with knuckle hyperpigmentation.

PMID- 29359057
TI  - A Triple Obstetric Challenge of Thoracopagus-Type Conjoined Twins, Eclampsia, and
      Obstructed Labor: A Case Report from Sub-Saharan Africa.
AB  - Conjoined twins are very rarely seen. We present a case of thoracopagus that was
      undiagnosed prior to delivery and combined with eclampsia and obstructed labor in
      a low-resource setting in sub-Saharan Africa. A 27-year-old pregnant woman was
      presented to the maternity emergency unit of Princess Christian Maternity
      Hospital (PCMH) in Freetown at term in labor. Upon admission, the patient was
      awake and orientated and presented a blood pressure of 180/120 mmHg and a protein
      value of 3+ on urine dipstick test. Clinical examination-ultrasound was not
      available-led to the admission diagnosis: obstructed labor with intrauterine
      fetal death and preeclampsia. Application of Hydralazine 5 mg (i.v.) under close
      blood pressure monitoring was performed. Under spontaneous progression of labor,
      one head of the yet unknown conjoined twin was born. The patient developed
      eclamptic fits. Ceasing of seizures was achieved after implementing the loading
      dose of the MgSO4 protocol. A vaginal examination led to the unexpected diagnosis
      of conjoined twins. An emergency cesarean section under general anesthesia via a
      longitudinal midline incision was performed immediately. The born head was
      repositioned vaginally. The stillborn conjoined twins presented a female
      thoracopagus type that seemed to involve the heart. After 8 weeks, the woman was
      clinically fully recovered.

PMID- 29359058
TI  - Facilitation of Vaginal Delivery in an Infant with Complete Heart Block Secondary
      to Maternal Anti-Ro Antibodies.
AB  - Congenital heart block (CHB) is a rare disorder that may be associated with a
      high morbidity and even mortality, with a risk of death both in utero and during
      infancy. Women with serum titres of anti-Ro and/or anti-La antibodies carry a
      risk of CHB of 1-5% in their offspring, with a recurrence risk of approximately
      20%. We present a case of a 36-year-old female with a pregnancy complicated by
      congenital heart block. Autoimmune profiling at booking showed she was positive
      for lupus anticoagulant and anti-Ro antibodies. A fetal echocardiogram at 21 + 3
      showed complete heart block. She was monitored throughout the remainder of her
      pregnancy with serial growth scans, cardiovascular profiling, and BPP scoring.
      She had a normal vaginal delivery at term to a female infant.

PMID- 29359059
TI  - Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell
      Cancer Patient.
AB  - Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the
      standard of care for patients with metastatic renal cell carcinoma. Renal adverse
      events associated with sunitinib include proteinuria, renal insufficiency
      secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic
      microangiopathy. We describe the second reported instance of biopsy-proven
      sunitinib-induced acute interstitial nephritis (AIN), in a challenging case
      complicated by thrombocytopenia. The case illustrates the importance of early
      diagnosis and intervention in ensuring long-term recovery from renal
      complications. Four other cases of AIN reported along with inhibition of the
      vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib)
      or antibodies (bevacizumab) suggest a possible class effect. Given our
      experience, we recommend monitoring renal function with VEGF inhibition, and in
      the case of renal failure in the setting of an unclear diagnosis, we recommend
      prompt biopsy.

PMID- 29359060
TI  - Corrigendum to "Revision of Carpal Tunnel Release due to Palmaris Longus
      Profundus".
AB  - [This corrects the article DOI: 10.1155/2015/616051.].

PMID- 29359061
TI  - Angiofibroma Localized in the Sphenoid Sinus.
AB  - Juvenile nasopharyngeal angiofibroma is the most common benign tumor of the
      nasopharynx with complaints of unilateral nasal obstruction and recurrent
      nosebleeds in the young male population. Despite being a benign tumor, it can be
      aggressively destructive in surrounding tissues and bones by acting locally. The
      gold standard treatment method is the surgical excision of the tumor. This case
      report is a case of angiofibroma, a 32-year-old asymptomatic male patient with no
      evidence of clinical signs and endoscopic examination, which is recognized as a
      localized vascular mass lesion in the right sphenoid sinus on the cranial MR
      imaging. We prepared this case report that may represent an angiofibroma
      localized only within the sphenoid sinus which is very rare in the literature.

PMID- 29359062
TI  - Uterine Arteriovenous Fistula with Concomitant Pelvic Varicocele: Endovascular
      Embolization with Onyx-18(r).
AB  - Uterine arteriovenous fistulas are rare and acquired causes of life-threatening
      vaginal bleeding. They usually present with intermittent menometrorrhagia in
      young patients in childbearing age with history of gynecological procedures on
      uterus. Traditional management is hysterectomy; endovascular embolization
      represents nowadays an alternative strategy for patients wishing to preserve
      fertility. Here, the endovascular approach to a 29-year-old woman affected by
      severe menometrorrhagia caused by a uterine arteriovenous fistula with a
      concomitant pelvic varicocele is reported; a bilateral uterine arteries
      embolization with Onyx-18 (ev3, Irvine, CA, USA) has successfully resolved the
      fistula with clinical success.

PMID- 29359063
TI  - Seeking a New Paradigm for Alzheimer's Disease: Considering the Roles of
      Inflammation, Blood-Brain Barrier Dysfunction, and Prion Disease.
AB  - There is no effective etiologic treatment for Alzheimer's disease, nor is there a
      prophylactic medication which delays or prevents its onset. The lack of an
      accurate paradigm is undoubtedly related to the lack of effective means of
      prophylaxis and treatment. The current paradigm of beta amyloid in Alzheimer's
      brains causing cognitive dysfunction must be modified. Despite failed clinical
      trials, research continues into amyloid-oriented treatments. The persistence of
      the amyloid hypothesis/paradigm is an example of anchoring and representativeness
      heuristics described by Kahneman and Tversky in their classic 1974 Science paper.
      Economic factors also contribute to the persistence of this paradigm. Paradigms
      impact the scientific process by the following: (1) what is studied; (2) the
      types of questions that are asked; (3) the structure and nature of the questions;
      (4) the interpretations of research findings. We review the contribution of
      inflammation, malfunction of the neurovascular unit, and prion disease to
      Alzheimer's disease manifestations. Any or all of these are candidates for
      inclusion into a more accurate, inclusive, and useful new paradigm. By
      incorporating emerging facts and understanding into a new paradigm, we will
      enhance our ability to move toward effective prophylaxis and therapy for this
      tragic disease.

PMID- 29359064
TI  - Corrigendum to "New Issues in the Management of Osteoporosis".
AB  - [This corrects the article DOI: 10.4061/2011/582789.].

PMID- 29359065
TI  - Cognitive Impact of Deep Brain Stimulation on Parkinson's Disease Patients.
AB  - Subthalamic nucleus (STN) or globus pallidus interna (GPi) deep brain stimulation
      (DBS) is considered a robust therapeutic tool in the treatment of Parkinson's
      disease (PD) patients, although it has been reported to potentially cause
      cognitive decline in some cases. We here provide an in-depth and critical review
      of the current literature regarding cognition after DBS in PD, summarizing the
      available data on the impact of STN and GPi DBS as monotherapies and also
      comparative data across these two therapies on 7 cognitive domains. We provide
      evidence that, in appropriately screened PD patients, worsening of one or more
      cognitive functions is rare and subtle after DBS, without negative impact on
      quality of life, and that there is very little data supporting that STN DBS has a
      worse cognitive outcome than GPi DBS.

PMID- 29359066
TI  - Theatre Is a Valid Add-On Therapeutic Intervention for Emotional Rehabilitation
      of Parkinson's Disease Patients.
AB  - Conventional medical treatments of Parkinson's disease (PD) are effective on
      motor disturbances but may have little impact on nonmotor symptoms, especially
      psychiatric ones. Thus, even when motor symptomatology improves, patients might
      experience deterioration in their quality of life. We have shown that 3 years of
      active theatre is a valid complementary intervention for PD as it significantly
      improves the well-being of patients in comparison to patients undergoing
      conventional physiotherapy. Our aim was to replicate these findings while
      improving the efficacy of the treatment. We ran a single-blinded pilot study
      lasting 15 months on 24 subjects with moderate idiopathic PD. 12 were assigned to
      a theatre program in which patients underwent "emotional" training. The other 12
      underwent group physiotherapy. Patients were evaluated at the beginning and at
      the end of their treatments, using a battery of eight clinical and five
      neuropsychological scales. We found that the emotional theatre training improved
      the emotional well-being of patients, whereas physiotherapy did not.
      Interestingly, neither of the groups showed improvements in either motor symptoms
      or cognitive abilities tested by the neuropsychological battery. We confirmed
      that theatre therapy might be helpful in improving emotional well-being in PD.

PMID- 29359068
TI  - Intensive Care Medicine: Organization, Education and Politics.

PMID- 29359067
TI  - Changes of Metabolomic Profile in Helianthus annuus under Exposure to
      Chromium(VI) Studied by capHPLC-ESI-QTOF-MS and MS/MS.
AB  - The application of capHPLC-ESI-QTOF-MS and MS/MS to study the impact of Cr(VI) on
      metabolites profile in Helianthus annuus is reported. Germinated seeds were grown
      hydroponically in the presence of Cr(VI) (25 mgCr/L) and root extracts of the
      exposed and control plants were analyzed by untargeted metabolomic approach. The
      main goal was to detect which metabolite groups were mostly affected by Cr(VI)
      stress; two data analysis tools (ProfileAnalysis, Bruker, and online XCMS) were
      used under criteria of intensity threshold 5 . 104 cps, fold change >= 5, and p
      <= 0.01, yielding precursor ions. Molecular formulas were assigned based on data
      processing with two computational tools (SIRIUS and MS-Finder); annotation of
      candidate structures was performed by database search using CSI:FingerID and MS
      Finder. Even though ultimate identification has not been achieved, it was
      demonstrated that secondary metabolism became activated under Cr(VI) stress.
      Among 42 candidate compounds returned from database search for seven molecular
      formulas, ten structures corresponded to isocoumarin derivatives and eleven were
      sesquiterpenes or sesquiterpene lactones; three benzofurans and four glycoside or
      pyrane derivatives of phenolic compounds were also suggested. To gain further
      insight on the effect of Cr(VI) in sunflower, isocoumarins and sesquiterpenes
      were selected as the target compounds for future study.

PMID- 29359069
TI  - Intensive Care Medicine: Different Recipes for Shared Goals.

PMID- 29359070
TI  - Noninvasive Ventilation in Hypoxemic Patients: an Ongoing Soccer Game or a Lost
      One?

PMID- 29359071
TI  - Noninvasive Ventilation for Acute Hypoxemic Respiratory Failure/ARDS - is There a
      Role?

PMID- 29359072
TI  - Efficacy and Safety of Using High-Flow Nasal Oxygenation in Patients Undergoing
      Rapid Sequence Intubation.
AB  - Objective: To assess the efficacy and safety of high-flow nasal oxygen (HFNO)
      therapy in patients undergoing rapid sequence intubation (RSI) for emergency
      abdominal surgery. Methods: HFNO of 60 L.min-1 at an inspiratory oxygen fraction
      of 1 was delivered 4 min before laryngoscopy and maintained until the patient was
      intubated, and correct intubation was verified by the appearance of the end-tidal
      CO2 (EtCO2) waveform. Transcutaneous oxygenation (SpO2), heart rate and non
      invasive mean arterial pressure were monitored at baseline (T0), after 4 min on
      HFNO (T1) and at the time of laryngoscopy (T2) and endotracheal intubation (ETI)
      (T3). An SpO2 of <3% from baseline was recorded at any sampled time. The value of
      EtCO2 at T3 was registered after two mechanical breaths. The apnoea time was
      defined as the time from the end of propofol injection to ETI. RSI was performed
      with propofol, fentanyl and rocuronium. Results: Forty-five patients were
      enrolled. SpO2 levels showed a statistically significant increase at T1, T2 and
      T3 compared with those at T0 (p<0.05); median SpO2% (interquartile range) was 97%
      (range, 96%-99%) at T0, 99% (range, 99%-100%) at T1, 99% (range, 99%-100%) at T2
      and 99% (range, 99%-100%) at T3. Minimal SpO2 was 96%; no patient showed an SpO2
      of <3% from baseline; mean EtCO2 at the time of ETI was 36+/-4 mmHg. Maximum
      apnoea time was 12 min. Conclusion: HFNO is an effective and safe technique for
      pre-oxygenation in patients undergoing rapid sequence induction of general
      anaesthesia for emergency surgery.

PMID- 29359073
TI  - Number of Prehospital Defibrillation Shocks and the Return of Spontaneous
      Circulation in Out-of-Hospital Cardiac Arrest.
AB  - Objective: It has not been determined yet whether the number of defibrillation
      shocks delivered over the first 30 min of cardiopulmonary resuscitation (CPR)
      impacts the rate of successful return of spontaneous circulation (ROSC) in out-of
      hospital cardiac arrest (OHCA). Methods: We conducted a retrospective
      observational study in non-traumatic OHCA. Patients who were administered
      defibrillation shocks using a public automated external defibrillator (AED) were
      consecutively enrolled in the study. We assessed the relationship between ROSC
      and the number of prehospital defibrillation shocks and constructed an receiver
      operating characteristic (ROC) curve to illustrate the ability of repeated
      defibrillation shocks to predict ROSC over the first 30 min of CPR. Results:
      Increasing the number of defibrillation shocks progressively decreased the
      probability to achieve ROSC. The highest rate of ROSC (33%) was observed when
      four shocks were delivered. The ROC curve illustrated that the fourth shock
      maximised sensitivity and specificity (area under the curve [AUC]=0.72). The
      positive and negative predictive values for ROSC reached 82% and 48%,
      respectively, when <4 shocks were delivered. Conclusion: The delivery of four
      defibrillation shocks in OHCA most related to ROSC. The evaluation of the number
      of delivered shock during the first 30 min of CPR is a simple tool that can be
      used for an early decision in OHCA patient.

PMID- 29359074
TI  - Association of Low Blood Pressure, Low Bispectral Index and Low Minimum Alveolar
      Concentration of Anaesthetic during Surgery with Postoperative 30-day Mortality:
      A Systemic Review and Meta-Analysis.
AB  - Objective: The triple low state [low mean arterial pressure, low bispectral index
      (BIS) and a low minimum alveolar concentration (MAC)] fraction of anaesthetic
      during surgery) has been a controversial subject of interest in clinical
      practise. Previous retrospective studies have produced different conclusions on
      the association between a triple low state and postoperative 30-day mortality.
      This study was a systematic review of previous studies on the effects of the
      triple low state on postoperative 30-day mortality and a meta-analysis with a
      sample size larger than that of previous studies. Methods: After searching for
      relevant articles in the PubMed database as on 27 March 2017, we included studies
      that compared postoperative 30-day mortality between triple low and non-triple
      low groups. The identified articles were subjected to an initial screening using
      keywords 'low bispectral index', 'intraoperative hypotension' and 'low minimum
      alveolar concentration' according to the PRISMA Flow diagram (2009). After a full
      text review, appropriate studies were finally included in our meta-analysis. All
      statistical analyses were performed using the R programme 3.3.2 and meta
      packages. Results: Three retrospective cohort studies were included in the meta
      analysis. The total number of subjects in the triple low and non-triple low
      groups was 29,402 and 17,428, respectively; the sample size was 46,830. We
      derived a hazard ratio (HR) of 1.09 [95% confidence interval (CI), 1.07-1.11)]
      for the fixed effect model and of 1.30 (95% CI, 1.04-1.07) for the random effect
      model. In the analysis of heterogeneity among the three studies, I2=95% was
      obtained (P<0.01). Thus, the values obtained from the random effect model were
      used; HR was 1.30 for the triple low group, indicating a 30% increase in the
      overall 30-day mortality. Conclusion: The present study demonstrated that
      patients exposed to the triple low state exhibit higher 30-day mortality rates
      than those not exposed to the triple low state.

PMID- 29359075
TI  - Examination of Changes in Infection Rates in a Restructured Anaesthesia Intensive
      Care Unit: A Retrospective Study.
AB  - Objective: This retrospective study aimed to evaluate the effect of a
      restructured anaesthesia intensive care unit (ICU) on changes in infection rates
      and infections. Methods: Organisational restructuring was done in the anaesthesia
      ICU of Firat University Hospital after it was relocated on 14 March 2012. This
      study was designed to investigate the effect of restructuring on infection rates
      through a comparison of periods encompassing one year before relocation and one
      year after relocation. Nosocomial infections were diagnosed according to modified
      Centers for Disease Control and Prevention (CDC) criteria. In total, 406 patients
      who were over 18 years old and admitted to the ICU were included; they were
      hospitalised for 48 h or longer and had non-infectious diseases according to
      physical examination, laboratory and culture results on admission. The data of
      214 patients (Group A) and 192 patients (Group B) were examined. Results:
      Parameters such as age, gender, primary diagnosis and mean GCS score at admission
      and mean duration of hospitalisation showed no effect on the rates of infection,
      but rates of total infection (41.1% vs. 25%), urinary (18.7% vs. 10.4%) and VIP
      (32.7% vs. 14.6%) were detected in Groups A and B. Statistically significant
      differences were found for the causative pathogens Pseudomonas (15.4% vs. 6.8%),
      Acinetobacter (18.2% vs. 12%) and Escherichia (8.9% vs. 2.1%); the mean duration
      of mechanical ventilation (15.01+/-16.681 vs. 12.22+/-17.595) and discharge with
      improvement (31.8% vs. 44.3%). Conclusion: We detected that restructuring (such
      as acclimatization, educated staff, hepa filter) caused a significant decline in
      infection rates. Because ICU staff may be a major cause of infection, we believe
      that providing education and conducting effective surveillance programs will be
      the most important factors for reducing infection rates.

PMID- 29359076
TI  - Effect of Cricoid Pressure on Laryngeal View During Macintosh, McGrath MAC X
      Blade and GlideScope Video Laryngoscopies.
AB  - Objective: Cricoid pressure is useful in fasted patients requiring emergency
      intubation. We compared the effect of cricoid pressure on laryngeal view during
      Macintosh, McGrath MAC X-Blade and GlideScope video laryngoscopy. Methods: After
      obtaining approval from the Human Research Ethics Committee and written informed
      consent from patients, we enrolled 120 patients (American Society of
      Anesthesiologists I-II, age 18-65 years) undergoing elective surgery that
      required endotracheal intubation in this prospective randomised study. Patients
      were divided into three groups (Macintosh, McGrath MAC X-Blade and GlideScope).
      Results: Demographic and airway variables were similar in the groups. Cormack
      Lehane grades were improved or unchanged on using cricoid pressure in Macintosh
      and McGrath MAC X-Blade groups. However, laryngeal views worsened in 12 patients
      (30%), remained unchanged in 26 patients (65%) and improved in 2 patients (5%) in
      the GlideScope group (p<0.001). Insertion and intubation times for Macintosh and
      McGrath MAC X-Blade video laryngoscopes were similar. Insertion times for
      GlideScope and Macintosh video laryngoscopes were similar, but were longer than
      those for the McGrath MAC X-Blade video laryngoscope (p=0.02). Tracheal
      intubation took longer with the GlideScope video laryngoscope than with the other
      devices (p<0.001 and p=0.003). Mean arterial pressures after insertion increased
      significantly in Macintosh and GlideScope groups (p=0.004 and p=0.001,
      respectively) compared with post-induction values. Heart rates increased after
      insertion in all three groups compared with post-induction values (p<0.001). Need
      for optimisation manoeuvres and postoperative minor complications were comparable
      in all three groups. Conclusion: Although all three devices are useful for normal
      or difficult intubation, cricoid pressure improved Cormack-Lehane grades of
      Macintosh and McGrath MAC X-Blade video laryngoscopes but statistically
      significantly worsened that of the GlideScope video laryngoscope.

PMID- 29359078
TI  - Anaesthetic Management of a Child with a Massive Mediastinal Mass.
AB  - Mediastinal masses are benign or malignant tumours that originate from the
      thymus, thyroid, lung, lymphoid system, pleura, or pericardium. Cardiovascular
      and respiratory symptoms may occur because of the compression of surrounding
      tissues along with growing mass. In this study, we present the anaesthetic
      management of a 6-month-old child having a massive anterior mediastinal mass that
      had a compressing effect.

PMID- 29359077
TI  - Assessment of Left Ventricular Dimensions by Transoesophageal Echocardiography in
      Patients During Coronary Artery Bypass Surgery.
AB  - Objective: Normative values of left ventricular (LV) end-diastolic area and
      diameter (EDA and EDD) for intraoperative transoesophageal echocardiography (TEE)
      have not been established. We aimed to define the ranges of LV EDA and EDD for
      intraoperative TEE examinations in patients undergoing coronary artery bypass
      graft (CABG) surgery. Methods: A MEDLINE search for studies reporting LV EDA and
      EDD in CABG patients was performed. Individual-level dataset from 333
      anaesthetised and mechanically ventilated patients with preserved LV function
      (study population) were received from 8 studies. EDA and calculated EDD values in
      the study population were compared with summary mean EDD values obtained by
      transthoracic echocardiography (TTE) in 2 studies of 500 awake patients with
      coronary artery disease (CAD). Further, the influence of prespecified factors on
      EDD was evaluated through a multivariate regression model. Results: LV EDA and
      EDD values measured by TEE in anaesthetised CABG patients were 16.7+/-4.7 cm2 and
      4.6+/-0.6 cm, respectively. EDD values measured by TEE in anaesthetised patients
      were 10% to 13% less those measured by TTE in 2 studies of awake patients
      (p<0.001). Body surface area, age and fractional area change but not sex were
      factors that affected LV EDD. Conclusion: LV EDD values measured by
      intraoperative TEE in anaesthetised and mechanically ventilated CABG patients
      were 10% to 13% less than those measured by TTE in awake CAD patients. This
      finding indicates that independent normative values specific for intraoperative
      TEE should be established for guiding intraoperative clinical decisions.

PMID- 29359079
TI  - Anti-N-Methyl-D-Aspartate-Receptor Encephalitis in Young Females.
AB  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an immune-mediated
      disease commonly associated with ovarian teratoma. Anti-NMDA-receptor
      autoantibodies disrupt NMDA function leading to the development of psychosis,
      seizures and autonomic dysfunction. The treatment includes underlying tumour
      resection and immunosuppression. Slow recovery and unpredictable clinical course
      makes intensive care management of these patients challenging. We report the
      management of two young female patients with anti-NMDA-receptor encephalitis
      associated with ovarian teratoma.

PMID- 29359080
TI  - Food Choking in a Patient with Congenital Temporomandibular Joint Ankylosis.

PMID- 29359081
TI  - A 61-Year-Old Caucasian Woman with Sarcoidosis.

PMID- 29359083
TI  - Phase distribution analysis of tissues based on the off-axis digital holographic
      hybrid reconstruction algorithm.
AB  - Off-axis digital holography (DH) has great potential in histopathology for its
      high efficiency and precision. Phase distribution, usually extracted by the
      angular spectrum (AS) algorithm from a digital hologram, reflects important
      structural information of biological tissues. However, the complex structure of
      tissues introduces spectrum aliasing of the hologram, making the AS algorithm
      hard to realize and accurate phase analysis difficult to conduct. Here, we
      present a hybrid reconstruction algorithm, combining Fresnel reconstruction in
      spatial domain with the AS algorithm in frequency domain, to solve aliasing by
      spatial filtering. Through simulation, we demonstrate the feasibility and
      superiority of the hybrid algorithm and verified the precision (10-3 rad) of the
      hybrid algorithm with spectrum aliasing. We extract phase distributions from
      normal urothelial and bladder cancer tissues by the hybrid algorithm and make
      quantitative analysis through histogram and standard deviation. The result shows
      the hybrid algorithm in off-axis DH has great advantage for the high-precision
      phase extraction of tissues and supplies significant information for cancer
      diagnosis.

PMID- 29359084
TI  - Label-free monitoring of cell death induced by oxidative stress in living human
      cells using terahertz ATR spectroscopy.
AB  - We demonstrated that attenuated total reflectance terahertz time-domain
      spectroscopy (ATR THz-TDS) is able to monitor oxidative stress response of living
      human cells, which is proven in this work that it is an efficient non-invasive,
      label-free, real-time and in situ monitoring of cell death. Furthermore, the
      dielectric constant and dielectric loss of cultured living human breast
      epithelial cells, and along with their evolution under oxidative stress response
      induced by high concentration of H2O2, were quantitatively determined in the
      work. Our observation and results were finally confirmed using standard
      fluorescence-labeled flow cytometry measurements and visible fluorescence
      imaging.

PMID- 29359085
TI  - Volumetric fluorescence retinal imaging in vivo over a 30-degree field of view by
      oblique scanning laser ophthalmoscopy (oSLO).
AB  - While fluorescent contrast is widely used in ophthalmology, three-dimensional
      (3D) fluorescence retinal imaging over a large field of view (FOV) has been
      challenging. In this paper, we describe a novel oblique scanning laser
      ophthalmoscopy (oSLO) technique that provides 3D volumetric fluorescence retinal
      imaging with only one raster scan. The technique utilizes scanned oblique
      illumination and angled detection to obtain fluorescent cross-sectional images,
      analogous to optical coherence tomography (OCT) line scans (or B-scans). By
      breaking the coaxial optical alignment used in conventional retinal imaging
      modalities, depth resolution is drastically improved. To demonstrate the
      capability of oSLO, we have performed in vivo volumetric fluorescein angiography
      (FA) of the rat retina with ~25MUm depth resolution and over a 30 degrees  FOV.
      Using depth segmentation, oSLO can obtain high contrast images of the
      microvasculature down to single capillaries in 3D. The multi-modal nature of oSLO
      also allows for seamless combination with simultaneous OCT angiography.

PMID- 29359086
TI  - Time-resolved near infrared light propagation using frequency domain
      superposition.
AB  - Time-resolved temporal point spread function (TPSF) measurement of near infrared
      spectroscopic (NIRS) data allows the estimation of absorption and reduced
      scattering properties of biological tissues. Such analysis requires an iterative
      calculation of the theoretical TPSF curve using mathematical and computational
      models of the domain being imaged which are computationally complex and
      expensive. In this work, an efficient methodology for representing the TPSF data
      using a superposition of cosines calculated in frequency domain is presented. The
      proposed method is outlined and tested on finite element realistic models of the
      human neck and head. Using an adult head model containing ~140k nodes, the TPSF
      calculation at each node for one source is accelerated from 3.11 s to 1.29 s
      within an error limit of +/- 5% related to the time domain calculation method.

PMID- 29359087
TI  - Correction of an adding-doubling inversion algorithm for the measurement of the
      optical parameters of turbid media.
AB  - We present broadband measurements of the optical properties of tissue-mimicking
      solid phantoms using a single integrating sphere to measure the hemispherical
      reflectance and transmittance under a direct illumination at the normal incident
      angle. These measurements are traceable to reflectance and transmittance scales.
      An inversion routine using the output of the adding-doubling algorithm restricted
      to the reflectance and transmittance under a direct illumination was developed to
      produce the optical parameters of the sample along with an uncertainty budget at
      each wavelength. The results for two types of phantoms are compared to
      measurements by time-resolved approaches. The results between our method and
      these independent measurements agree within the estimated measurement
      uncertainties.

PMID- 29359088
TI  - Quantitative observations on cytoskeleton changes of osteocytes at different cell
      parts using digital holographic microscopy.
AB  - Cytoskeletons such as F-actin have different distributions in different cell
      parts and they are the cause of different degrees of cell collapse when the F
      actin is disrupted. It is challenging to use conventional methods such as
      fluorescence microscopy and atomic force microscopy to conduct real-time and
      three-dimensional observations on the dynamic processes at different cell parts
      due to the slow measuring speed and the need for live-cell staining. In this
      study, the morphological variations of different bone cell parts caused by F
      actin disruption are dynamically measured by using digital holographic microscopy
      (DHM). We separately analyze local parameters (cell height and cell width) and
      global parameters (cell projected area and cell volume) of cells to address
      variations of specific cell areas and quantify the changing process of the whole
      cell. We found significant differences in temporal variations of both local and
      global cell parameters between the cell body and cell process, which is
      consistent with the qualitative observation by fluorescence staining. Our study
      not only validates the unique ability of DHM to simultaneously investigate the
      dynamic process at different cell parts, but also provides sufficient
      experimental bases for exploring the mechanism for F-actin disruption.

PMID- 29359089
TI  - Comparison of tissue oximeters on a liquid phantom with adjustable optical
      properties: an extension.
AB  - Cerebral near-infrared spectroscopy (NIRS) oximetry may help clinicians to
      improve patient treatment. However, the application of NIRS oximeters is
      increasingly causing confusion to the users due to the inconsistency of tissue
      oxygen haemoglobin saturation (StO2) readings provided by different oximeters. To
      establish a comparability of oximeters, in our study we performed simultaneous
      measurements on the liquid phantom mimicking properties of neonatal heads and
      compared the tested device to a reference NIRS oximeter (OxiplexTS). We evaluated
      the NIRS oximeters FORE-SIGHT, NIRO and SenSmart, and reproduced previous results
      with the INVOS and OxyPrem v1.3 oximeters. In general, linear relationships of
      the StO2 values with respect to the reference were obtained. Device specific
      hypoxic and hyperoxic thresholds (as used in the SafeBoosC study,
      www.safeboosc.eu) and a table allowing for conversion of StO2 values are
      provided.

PMID- 29359090
TI  - Camera-based pulse-oximetry - validated risks and opportunities from theoretical
      analysis.
AB  - Camera-based pulse-oximetry has recently shown to be feasible, even when the
      signal is corrupted by noise and motion artifacts. Earlier work showed that using
      three instead of the common two wavelengths improves robustness of the
      measurement, however without a thorough investigation on the optimal wavelength
      selection. We therefore performed a search to identify these wavelengths to
      further improve the robustness of the measurement. Besides motion, it is
      empirically known that there are several other factors that influence the
      measurement leading to falsely-low or falsely-high SpO2 readings. These factors
      include the presence of dyshemoglobins or other species. In this paper, we use a
      theoretical skin-model to study how these factors influence the measurement, and
      how a proper wavelength selection can reduce the impact on the measurement.
      Additionally, we show that adding a third wavelength does not only improve
      robustness, but can also be exploited to create a reliability index for the
      measurement. Finally, we show that the presence of dyshemoglobins in arterial
      blood can not only be detected but also quantified. We illustrate this by
      comparing the estimated COHb levels of a small group of smokers and non-smokers,
      which typically have different CO-levels.

PMID- 29359091
TI  - High-resolution retinal swept source optical coherence tomography with an ultra
      wideband Fourier-domain mode-locked laser at MHz A-scan rates.
AB  - We present a new 1060 nm Fourier domain mode locked laser (FDML laser) with a
      record 143 nm sweep bandwidth at 2? 417 kHz  =  834 kHz and 120 nm at 1.67 MHz,
      respectively. We show that not only the bandwidth alone, but also the shape of
      the spectrum is critical for the resulting axial resolution, because of the
      specific wavelength-dependent absorption of the vitreous. The theoretical limit
      of our setup lies at 5.9 um axial resolution. In vivo MHz-OCT imaging of human
      retina is performed and the image quality is compared to the previous results
      acquired with 70 nm sweep range, as well as to existing spectral domain OCT data
      with 2.1 um axial resolution from literature. We identify benefits of the higher
      resolution, for example the improved visualization of small blood vessels in the
      retina besides several others.

PMID- 29359092
TI  - Concurrent measurement of skeletal muscle blood flow during exercise with diffuse
      correlation spectroscopy and Doppler ultrasound.
AB  - Noninvasive, direct measurement of local muscle blood flow in humans remains
      limited. Diffuse correlation spectroscopy (DCS) is an emerging technique to
      measure regional blood flow at the microvascular level. In order to better
      understand the strengths and limitations of this novel technique, we performed a
      validation study by comparing muscle blood flow changes measured with DCS and
      Doppler ultrasound during exercise. Nine subjects were measured (all males, 27.4
      +/- 2.9 years of age) for a rhythmic handgrip exercise at 20% and 50% of
      individual maximum voluntary contraction (MVC), followed by a post-exercise
      recovery. The results from DCS and Doppler ultrasound were highly correlated (R =
      0.99 +/- 0.02). DCS was more reliable and less susceptible to motion artifact.

PMID- 29359093
TI  - Towards two-photon excited endogenous fluorescence lifetime imaging
      microendoscopy.
AB  - In situ fluorescence lifetime imaging microscopy (FLIM) in an endoscopic
      configuration of the endogenous biomarker nicotinamide adenine dinucleotide
      (NADH) has a great potential for malignant tissue diagnosis. Moreover, two-photon
      nonlinear excitation provides intrinsic optical sectioning along with enhanced
      imaging depth. We demonstrate, for the first time to our knowledge, nonlinear
      endogenous FLIM in a fibered microscope with proximal detection, applied to NADH
      in cultured cells, as a first step to a nonlinear endomicroscope, using a double
      clad microstructured fiber with convenient fiber length (> 3 m) and excitation
      pulse duration (~50 fs). Fluorescence photons are collected by the fiber inner
      cladding and we show that its contribution to the impulse response function
      (IRF), which originates from its intermodal and chromatic dispersions, is small
      (< 600 ps) and stable for lengths up to 8 m and allows for short lifetime
      measurements. We use the phasor representation as a quick visualization tool
      adapted to the endoscopy speed requirements.

PMID- 29359094
TI  - Ultra-high contrast retinal display system for single photoreceptor
      psychophysics.
AB  - Due to the enormous dynamic range of human photoreceptors in response to light,
      studying their visual function in the intact retina challenges the stimulation
      hardware, specifically with regard to the displayable luminance contrast. The
      adaptive optics scanning laser ophthalmoscope (AOSLO) is an optical platform that
      focuses light to extremely small retinal extents, approaching the size of single
      photoreceptor cells. However, the current light modulation techniques produce
      spurious visible backgrounds which fundamentally limit experimental options. To
      remove unwanted background light and to improve contrast for high dynamic range
      visual stimulation in an AOSLO, we cascaded two commercial fiber-coupled acousto
      optic modulators (AOMs) and measured their combined optical contrast. By
      compensating for zero-point differences in the individual AOMs, we demonstrate a
      multiplicative extinction ratio in the cascade that was in accordance with the
      extinction ratios of both single AOMs. When latency differences in the AOM
      response functions were individually corrected, single switch events as short as
      50 ns with radiant power contrasts up to 1:1010 were achieved. This is the
      highest visual contrast reported for any display system so far. We show
      psychophysically that this contrast ratio is sufficient to stimulate single
      foveal photoreceptor cells with small and bright enough visible targets that do
      not contain a detectable background. Background-free stimulation will enable
      photoreceptor testing with custom adaptation lights. Furthermore, a larger
      dynamic range in displayable light levels can drive photoreceptor responses in
      cones as well as in rods.

PMID- 29359095
TI  - Quantization of collagen organization in the stroma with a new order coefficient.
AB  - Many optical and biomechanical properties of the cornea, specifically the
      transparency of the stroma and its stiffness, can be traced to the degree of
      order and direction of the constituent collagen fibers. To measure the degree of
      order inside the cornea, a new metric, the order coefficient, was introduced to
      quantify the organization of the collagen fibers from images of the stroma
      produced with a custom-developed second harmonic generation microscope. The order
      coefficient method gave a quantitative assessment of the differences in stromal
      collagen arrangement across the cornea depths and between untreated stroma and
      cross-linked stroma.

PMID- 29359096
TI  - Development of a real-time and quantitative thrombus sensor for an extracorporeal
      centrifugal blood pump by near-infrared light.
AB  - We developed an optical thrombus sensor for a monopivot extracorporeal
      centrifugal blood pump. In this study, we investigated its quantitative
      performance for thrombus detection in acute animal experiments of left
      ventricular assist using the pump on pathogen-free pigs. Optical fibers were set
      in the driver unit of the pump. The incident light at the near-infrared
      wavelength of 810 nm was aimed at the pivot bearing, and the resulting scattered
      light was guided to the optical fibers. The detected signal was analyzed to
      obtain the thrombus formation level. As a result, real-time and quantitative
      monitoring of the thrombus surface area on the pivot bearing was achieved with an
      accuracy of 3.6 +/- 2.3 mm2. In addition, the sensing method using the near
      infrared light was not influenced by changes in the oxygen saturation and the
      hematocrit. It is expected that the developed sensor will be useful for optimal
      anticoagulation management for long-term extracorporeal circulation therapies.

PMID- 29359097
TI  - High-resolution imaging in two-photon excitation microscopy using in situ
      estimations of the point spread function.
AB  - We present a technique for improving the spatial resolution of two-photon
      excitation microscopy; our technique combines annular illumination with an in
      situ estimation of the point spread function (PSF) used for deconvolution. For
      the in situ estimation of the PSF, we developed a technique called
      autocorrelation scanning, in which a sample is imaged by the scanning of two
      excitation foci that are overlapped over various distances. The image series
      obtained with the variation of the distance between the two foci provides the
      autocorrelation function of the PSF, which can be used to estimate the PSF at
      specific positions within a sample. We proved the principle and the effectiveness
      of this technique through observations of a fluorescent biological sample, and we
      confirmed that the improvement in the spatial resolution was ~1.7 times that of
      typical two-photon excitation microscopy by observing a mouse brain phantom at a
      depth of 200 um.

PMID- 29359098
TI  - Label-free imaging of atherosclerotic plaques using third-harmonic generation
      microscopy.
AB  - Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300
      nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human
      samples. Third harmonic generation (THG) from atherosclerotic plaques revealed
      morphological details of cellular and extracellular lipid deposits. Simultaneous
      nonlinear optical signals from the same laser source, including second harmonic
      generation and endogenous fluorescence, resulted in label-free images of various
      layers within the diseased vessel wall. The THG signal adds an endogenous
      contrast mechanism with a practical degree of specificity for atherosclerotic
      plaques that complements current nonlinear optical methods for the investigation
      of cardiovascular disease. Our use of whole-mount tissue and backward scattered
      epi-detection suggests THG could potentially be used in the future as a clinical
      tool.

PMID- 29359099
TI  - Simultaneous acquisition of neuronal morphology and cytoarchitecture in the same
      Golgi-stained brain.
AB  - Acquiring an accurate orientation reference is a prerequisite for precisely
      analysing the morphological features of Golgi-stained neurons in the whole brain.
      However, the same reflective imaging contrast of Golgi staining for morphology
      and Nissl staining for cytoarchitecture leads to the failure of distinguishing
      soma morphology and simultaneously co-locate cytoarchitecture. Here, we developed
      the dual-mode micro-optical sectioning tomography (dMOST) method to
      simultaneously image the reflective and fluorescent signals in three dimensions.
      We evaluated the feasibility of real-time fluorescent counterstaining on Golgi
      stained brain tissue. With our system, we acquired whole-brain data sets of
      physiological and pathological Golgi-stained mouse model brains with fluorescence
      labelled anatomical annotation at single-neuron resolution. We also obtained the
      neuronal morphology of macaque monkey brain tissue using this method. The results
      show that real-time acquisition of the co-located cytoarchitecture reference in
      the same brain greatly facilitates the precise morphological analysis of Golgi
      stained neurons.

PMID- 29359100
TI  - Fast epi-detected broadband multiplex CARS and SHG imaging of mouse skull cells.
AB  - We present a bimodal imaging system able to obtain epi-detected mutiplex coherent
      anti-Stokes Raman scattering (M-CARS) and second harmonic generation (SHG)
      signals coming from biological samples. We studied a fragment of mouse parietal
      bone and could detect broadband anti-Stokes and SHG responses originating from
      bone cells and collagen respectively. In addition we compared two post-processing
      methods to retrieve the imaginary part of the third-order nonlinear
      susceptibility related to the spontaneous Raman scattering.

PMID- 29359101
TI  - Two-photon deep-tissue spatially resolved mitochondrial imaging using membrane
      potential fluorescence fluctuations.
AB  - Cell metabolism and viability are directly reflected in their mitochondria.
      Imaging-based analysis of mitochondrial morphological structure, size and dynamic
      characteristics can therefore provide critical insight into cell function.
      However, mitochondria are often very abundant, and due to their close to
      diffraction-limit size, it is often non-trivial to distinguish a tubular or large
      mitochondrion from an ensemble of punctate mitochondria. In this paper, we use
      membrane potential dependent fluorescence fluctuations of individual mitochondria
      to resolve them using an approach similar to single molecule localization
      microscopy. We use 2-photon microscopy to image mitochondrial intensity
      fluctuations at 200 MUm deep inside an intact in-vivo mouse soleus muscle. By
      analyzing the acquired images, we can reconstruct images with an extra layer of
      information about individual mitochondria, separated from their ensemble. Our
      analysis shows a factor of 14 improvement in detection of mitochondria.

PMID- 29359102
TI  - 13-fold resolution gain through turbid layer via translated unknown speckle
      illumination.
AB  - Fluorescence imaging through a turbid layer holds great promise for various
      biophotonics applications. Conventional wavefront shaping techniques aim to
      create and scan a focus spot through the turbid layer. Finding the correct input
      wavefront without direct access to the target plane remains a critical challenge.
      In this paper, we explore a new strategy for imaging through turbid layer with a
      large field of view. In our setup, a fluorescence sample is sandwiched between
      two turbid layers. Instead of generating one focus spot via wavefront shaping, we
      use an unshaped beam to illuminate the turbid layer and generate an unknown
      speckle pattern at the target plane over a wide field of view. By tilting the
      input wavefront, we raster scan the unknown speckle pattern via the memory effect
      and capture the corresponding low-resolution fluorescence images through the
      turbid layer. Different from the wavefront-shaping-based single-spot scanning,
      the proposed approach employs many spots (i.e., speckles) in parallel for
      extending the field of view. Based on all captured images, we jointly recover the
      fluorescence object, the unknown optical transfer function of the turbid layer,
      the translated step size, and the unknown speckle pattern. Without direct access
      to the object plane or knowledge of the turbid layer, we demonstrate a 13-fold
      resolution gain through the turbid layer using the reported strategy. We also
      demonstrate the use of this technique to improve the resolution of a low
      numerical aperture objective lens allowing to obtain both large field of view and
      high resolution at the same time. The reported method provides insight for
      developing new fluorescence imaging platforms and may find applications in deep
      tissue imaging.

PMID- 29359103
TI  - Multispectral photoacoustic microscopy of lipids using a pulsed supercontinuum
      laser.
AB  - We demonstrate optical resolution photoacoustic microscopy (OR-PAM) of lipid-rich
      tissue between 1050-1714 nm using a pulsed supercontinuum laser based on a large
      mode-area photonic crystal fiber. OR-PAM experiments of lipid-rich samples show
      the expected optical absorption peaks near 1210 and 1720 nm. These results show
      that pulsed supercontinuum lasers are promising for OR-PAM applications such as
      label-free histology of lipid-rich tissue and imaging small animal models of
      disease.

PMID- 29359104
TI  - Noninvasive glucose monitoring using mid-infrared absorption spectroscopy based
      on a few wavenumbers.
AB  - A method for performing noninvasive blood glucose measurements was developed. The
      method is based on mid-infrared absorption spectroscopy and uses only a few
      wavenumbers to measure blood glucose levels in vivo unconditionally. We found
      that the regression of blood glucose levels using only three wavenumbers, which
      were selected using a series cross-validation technique, realized accuracies
      comparable to those of cases in which a greater number of wavenumbers are used.
      In addition, we demonstrated the performance of this model through correlations
      among different types of data.

PMID- 29359105
TI  - Visualization of barriers and obstacles to molecular diffusion in live cells by
      spatial pair-cross-correlation in two dimensions.
AB  - Despite recent advances in optical super-resolution, we lack a method that can
      visualize the path followed by diffusing molecules in the cytoplasm or in the
      nucleus of cells. Fluorescence correlation spectroscopy (FCS) provides molecular
      dynamics at the single molecule level by averaging the behavior of many molecules
      over time at a single spot, thus achieving very good statistics but at only one
      point in the cell. Earlier image-based methods including raster-scan and
      spatiotemporal image correlation need spatial averaging over relatively large
      areas, thus compromising spatial resolution. Here, we use spatial pair-cross
      correlation in two dimensions (2D-pCF) to obtain relatively high resolution
      images of molecular diffusion dynamics and transport in live cells. The 2D-pCF
      method measures the time for a particle to go from one location to another by
      cross-correlating the intensity fluctuations at specific points in an image.
      Hence, a visual map of the average path followed by molecules is created.

PMID- 29359106
TI  - Compact, multi-exposure speckle contrast optical spectroscopy (SCOS) device for
      measuring deep tissue blood flow.
AB  - Speckle contrast optical spectroscopy (SCOS) measures absolute blood flow in deep
      tissue, by taking advantage of multi-distance (previously reported in the
      literature) or multi-exposure (reported here) approach. This method promises to
      use inexpensive detectors to obtain good signal-to-noise ratio, but it has not
      yet been implemented in a suitable manner for a mass production. Here we present
      a new, compact, low power consumption, 32 by 2 single photon avalanche diode
      (SPAD) array that has no readout noise, low dead time and has high sensitivity in
      low light conditions, such as in vivo measurements. To demonstrate the capability
      to measure blood flow in deep tissue, healthy volunteers were measured, showing
      no significant differences from the diffuse correlation spectroscopy. In the
      future, this array can be miniaturized to a low-cost, robust, battery operated
      wireless device paving the way for measuring blood flow in a wide-range of
      applications from sport injury recovery and training to, on-field concussion
      detection to wearables.

PMID- 29359107
TI  - FIMic: design for ultimate 3D-integral microscopy of in-vivo biological samples.
AB  - In this work, Fourier integral microscope (FIMic), an ultimate design of 3D
      integral microscopy, is presented. By placing a multiplexing microlens array at
      the aperture stop of the microscope objective of the host microscope, FIMic shows
      extended depth of field and enhanced lateral resolution in comparison with
      regular integral microscopy. As FIMic directly produces a set of orthographic
      views of the 3D-micrometer-sized sample, it is suitable for real-time imaging.
      Following regular integral-imaging reconstruction algorithms, a 2.75-fold
      enhanced depth of field and [Formula: see text]-time better spatial resolution in
      comparison with conventional integral microscopy is reported. Our claims are
      supported by theoretical analysis and experimental images of a resolution test
      target, cotton fibers, and in-vivo 3D-imaging of biological specimens.

PMID- 29359108
TI  - Dioptric defocus maps across the visual field for different indoor environments.
AB  - One of the factors proposed to regulate the eye growth is the error signal
      derived from the defocus in the retina and actually, this might arise from
      defocus not only in the fovea but the whole visual field. Therefore, myopia could
      be better predicted by spatio-temporally mapping the 'environmental defocus' over
      the visual field. At present, no devices are available that could provide this
      information. A 'Kinect sensor v1' camera (Microsoft Corp.) and a portable eye
      tracker were used for developing a system for quantifying 'indoor defocus error
      signals' across the central 58 degrees  of the visual field. Dioptric differences
      relative to the fovea (assumed to be in focus) were recorded over the visual
      field and 'defocus maps' were generated for various scenes and tasks.

PMID- 29359110
TI  - The Interrelationship between Refractive Error, Blood Vessel Anatomy, and
      Glaucomatous Visual Field Loss.
AB  - Purpose: We quantified the interrelationship between retinal blood vessel (BV)
      anatomical variation, spherical equivalent (SE) of refractive error, and
      functional diagnostic parameters in glaucoma to identify optimal parameters for
      the improvement of optical coherence tomography (OCT) retinal nerve fiber layer
      thickness (RNFLT) norms. Methods: A trained observer marked the intersections of
      the main superior/inferior temporal arteries and veins with concentric circles
      around the optic nerve head (ONH) center on fundus images. The interrelationship
      of BV, SE, and visual field global parameters was analyzed by multivariate
      regression and model comparison. Results: A total of 445 eyes of 445 patients in
      a large glaucoma practice were selected. Of all investigated BV parameters,
      interartery angles (IAA) between superior and inferior arteries at a radius of
      1.73 mm around the ONH center demonstrated the strongest relationship to SE
      (Bayesian information criterion difference to null model, 11.9). SE and BV
      parameters are unrelated to functional parameters, including mean deviation (MD),
      pattern standard deviation, and glaucoma hemifield test results. Conclusions: BV
      locations outside the ONH are sufficiently stable over glaucoma severity to
      represent individual eye anatomy, and the IAA at 1.73 mm eccentricity is the
      optimal parameter to be considered for novel OCT RNFLT norms. Translational
      Relevance: Among a large set of BV location parameters, considering IAA may
      improve RNFLT norms optimally and thereby increase the accuracy of clinical
      glaucoma diagnosis.

PMID- 29359109
TI  - Proteome and Metabolome of Subretinal Fluid in Central Serous Chorioretinopathy
      and Rhegmatogenous Retinal Detachment: A Pilot Case Study.
AB  - Purpose: To investigate the molecular composition of subretinal fluid (SRF) in
      central serous chorioretinopathy (CSCR) and rhegmatogenous retinal detachment
      (RRD) using proteomics and metabolomics. Methods: SRF was obtained from one
      patient with severe nonresolving bullous CSCR requiring surgical subretinal
      fibrin removal, and two patients with long-standing RRD. Proteins were trypsin
      digested, labeled with Tandem-Mass-Tag and fractionated according to their
      isoelectric point for identification and quantification by tandem mass
      spectrometry. Independently, metabolites were extracted on cold methanol/ethanol,
      and identified by untargeted ultra-high performance liquid chromatography and
      high-resolution mass spectrometry. Bioinformatics analyses were conducted.
      Results: In total, 291 proteins and 651 metabolites were identified in SRF
      samples. Compared with RRD, 128 proteins (77 downregulated; 51 upregulated) and
      76 metabolites (43 downregulated; 33 upregulated) differed in the SRF from CSCR.
      Protein and metabolites notably deregulated in CSCR were related to
      glycolysis/gluconeogenesis, inflammation (including serum amyloid P component,
      versican), alternative complement pathway (complement factor H and complement
      factor H-related protein), cellular adhesion, biliary acid metabolism (farnesoid
      X receptor/retinoid X receptor), and gluco- and mineralocorticoid systems
      (aldosterone, angiotensin, and corticosteroid-binding globulin). Conclusions:
      Proteomics and metabolomics can be performed on SRF. A unique SRF sample from
      CSCR exhibited a distinct molecular profile compared with RRD. Translational
      Relevance: This first comparative multiomics analysis of SRF improved the
      understanding of CSCR and RRD pathophysiology. It identified pathways potentially
      involved in the better photoreceptor preservation in CSCR, suggesting
      neuroprotective targets that will require additional confirmation.

PMID- 29359111
TI  - Driving With Hemianopia VI: Peripheral Prisms and Perceptual-Motor Training
      Improve Detection in a Driving Simulator.
AB  - Purpose: Drivers with homonymous hemianopia (HH) were previously found to have
      impaired detection of blind-side hazards, yet in many jurisdictions they may
      obtain a license. We evaluated whether oblique 57Delta peripheral prisms (p
      prisms) and perceptual-motor training improved blind-side detection rates.
      Methods: Patients with HH (n = 11) wore p-prisms for 2 weeks and then received
      perceptual-motor training (six visits) detecting and touching stimuli in the
      prism-expanded vision. In a driving simulator, patients drove and pressed the
      horn upon detection of pedestrians who ran toward the roadway (26 from each
      side): (1) without p-prisms at baseline; (2) with p-prisms after 2 weeks
      acclimation but before training; (3) with p-prisms after training; and (4) 3
      months later. Results: P-prisms improved blind-side detection from 42% to 56%,
      which further improved after training to 72% (all P < 0.001). Blind-side timely
      responses (adequate time to have stopped) improved from 31% without to 44% with p
      prisms (P < 0.001) and further improved with training to 55% (P = 0.02). At the 3
      month follow-up, improvements from training were maintained for detection (65%; P
      = 0.02) but not timely responses (P = 0.725). There was wide between-subject
      variability in baseline detection performance and response to p-prisms. There
      were no negative effects of p-prisms on vehicle control or seeing-side
      performance. Conclusions: P-prisms improved detection with no negative effects,
      and training may provide additional benefit. Translational Relevance: In
      jurisdictions where people with HH are legally driving, these data aid in
      clinical decision making by providing evidence that p-prisms improve performance
      without negative effects.

PMID- 29359112
TI  - Renal tumor with pancreatic metastasis: About a case report.

PMID- 29359113
TI  - Unilateral proptosis as initial presenting sign of prostate cancer in a 45-year
      old man.
AB  - We describe the case of 45-year-old man presented with a 3-month history of
      progressive unilateral proptosis, voiding symptoms, and a 20-pound weight loss.
      Imaging showed a large brain mass as well as significant extra cranial
      involvement. He was diagnosed with metastatic prostatic adenocarcinoma and
      underwent craniotomy, androgen deprivation therapy, and chemotherapy.

PMID- 29359114
TI  - Metastasis of Ta low-grade bladder cancer into the lung and paraneoplastic
      syndrome without local invasion: A case report and literature review.

PMID- 29359115
TI  - Painless vascular leiomyoma found after incision of the vaginal wall: A case
      report.

PMID- 29359116
TI  - Xanthogranuloma of the epididymis.

PMID- 29359119
TI  - Awareness, self-management behaviors, health literacy and kidney function
      relationships in specialty practice.
AB  - AIM: To determine the relationship between chronic kidney disease (CKD) awareness
      (CKD-A), self-management behaviors (CKD-SMB) knowledge, performance of CKD-SMBs,
      health literacy (HL) and kidney function. METHODS: Participants were eligible
      patients attending an outpatient nephrology clinic. Participants were
      administered: Newest Vital Sign to measure HL, CKD self-management knowledge tool
      (CKD-SMKT) to assess knowledge, past performance of CKD-SMB, CKD-A. Estimated GFR
      (eGFR) was determined using the MDRD-4 equation. Duration of clinic participation
      and CKD cause were extracted from medical charts. RESULTS: One-hundred-fifty
      patients participated in the study. eGFRs ranged from 17-152 mL/min per 1.73 m2.
      Majority (83%) of respondents had stage 3 or 4 CKD, low HL (63%), and were CKD
      aware (88%). Approximately 40% (10/25) of patients in stages 1 and 2 and 6.4%
      (8/125) in stages 3 and 4 were unaware of their CKD. CKD-A differed with stage (P
      < 0.001) but not by HL level, duration of clinic participation, or CKD cause.
      Majority of respondents (>= 90%) correctly answered one or more CKD-SMKT items.
      Knowledge of one behavior, "controlling blood pressure" differed significantly by
      CKD-A. CKD-A was associated with past performance of two CKD-SMBs, "controlling
      blood pressure" (P = 0.02), and "keeping healthy body weight" (P = 0.01).
      Adjusted multivariate analyses between CKD-A and: (1) HL; and (2) CKD-SMB
      knowledge were non-significant. However, there was a significant relationship
      between CKD-A and kidney function after controlling for demographics, HL, and CKD
      SMB (P < 0.05). CONCLUSION: CKD-A is not associated with HL, or better CKD-SMBs.
      CKD-A is significantly associated with kidney function and substantially lower
      eGFR, suggesting the need for focused patient education in CKD stages 1.

PMID- 29359118
TI  - Immunoglobulin G4-related kidney diseases: An updated review.
AB  - This review will encompass definition, pathogenesis, renal clinical
      manifestations and treatment of immunoglobulin G4-related diseases (IgG4-RDs).
      IgG4-RD is a recently recognized clinical entity that often involves multiple
      organs and is characterized by high levels of serum immunoglobulins G4, dense
      infiltration of IgG4+ cells and storiform fibrosis. Cellular immunity,
      particularly T-cell mediated immunity, has been implicated in the pathogenesis of
      IgG4-RDs. The most frequent renal manifestations of IgG4-RD are IgG4-related
      tubulointerstitial nephritis, membranous glomerulopathy and obstructive
      nephropathy secondary to urinary tract obstruction due to IgG4-related
      retroperitoneal fibrosis. IgG4-RD diagnosis should be based on specific
      histopathological findings, confirmed by tissue immunostaining, typical
      radiological findings and an appropriate clinical context. The first line
      treatment is the steroids with two warnings: Steroid resistance and relapse after
      discontinuation. In the case of steroid resistance, B cell depleting agents as
      rituximab represent the second-line treatment. In the case of relapse after
      discontinuation, steroid treatment may be associated with steroid sparing agents.
      Since the disease has been only recently identified, more prospective, long-term
      studies are needed to an improved understanding and a more correct and safe
      treatment.

PMID- 29359120
TI  - Synchronous Supraglottic and Esophageal Squamous Cell Carcinomas Treated with a
      Monoisocentric Hybrid Intensity-Modulated Radiation Technique.
AB  - Risk factors for squamous cell carcinomas (SCCs) of the head and neck (HN) and
      esophagus are similar. As such, synchronous primary tumors in these areas are not
      entirely uncommon. Definitive chemoradiation (CRT) is standard care for locally
      advanced HNSCC and is a preferred option for inoperable esophageal SCC.
      Simultaneous treatment of both primaries with CRT can present technical
      challenges. We report a case of synchronous supraglottic and esophageal SCC
      primary tumors, highlighting treatment with a monoisocentric hybrid radiation
      technique and normal tissue toxicity considerations.

PMID- 29359121
TI  - Radiobiological Optimization in Lung Stereotactic Body Radiation Therapy: Are We
      Ready to Apply Radiobiological Models?
AB  - Lung tumors are often associated with a poor prognosis although different
      schedules and treatment modalities have been extensively tested in the clinical
      practice. The complexity of this disease and the use of combined therapeutic
      approaches have been investigated and the use of high dose-rates is emerging as
      effective strategy. Technological improvements of clinical linear accelerators
      allow combining high dose-rate and a more conformal dose delivery with accurate
      imaging modalities pre- and during therapy. This paper aims at reporting the
      state of the art and future direction in the use of radiobiological models and
      radiobiological-based optimizations in the clinical practice for the treatment of
      lung cancer. To address this issue, a search was carried out on PubMed database
      to identify potential papers reporting tumor control probability and normal
      tissue complication probability for lung tumors. Full articles were retrieved
      when the abstract was considered relevant, and only papers published in English
      language were considered. The bibliographies of retrieved papers were also
      searched and relevant articles included. At the state of the art, dose-response
      relationships have been reported in literature for local tumor control and
      survival in stage III non-small cell lung cancer. Due to the lack of published
      radiobiological models for SBRT, several authors used dose constraints and models
      derived for conventional fractionation schemes. Recently, several radiobiological
      models and parameters for SBRT have been published and could be used in
      prospective trials although external validations are recommended to improve the
      robustness of model predictive capability. Moreover, radiobiological-based
      functions have been used within treatment planning systems for plan optimization
      but the advantages of using this strategy in the clinical practice are still
      under discussion. Future research should be directed toward combined regimens, in
      order to potentially improve both local tumor control and survival. Indeed,
      accurate knowledge of the relevant parameters describing tumor biology and normal
      tissue response is mandatory to correctly address this issue. In this context,
      the role of medical physicists and the AAPM in the development of radiobiological
      models is crucial for the progress of developing specific tool for
      radiobiological-based optimization treatment planning.

PMID- 29359117
TI  - Fluid balance concepts in medicine: Principles and practice.
AB  - The regulation of body fluid balance is a key concern in health and disease and
      comprises three concepts. The first concept pertains to the relationship between
      total body water (TBW) and total effective solute and is expressed in terms of
      the tonicity of the body fluids. Disturbances in tonicity are the main factor
      responsible for changes in cell volume, which can critically affect brain cell
      function and survival. Solutes distributed almost exclusively in the
      extracellular compartment (mainly sodium salts) and in the intracellular
      compartment (mainly potassium salts) contribute to tonicity, while solutes
      distributed in TBW have no effect on tonicity. The second body fluid balance
      concept relates to the regulation and measurement of abnormalities of sodium salt
      balance and extracellular volume. Estimation of extracellular volume is more
      complex and error prone than measurement of TBW. A key function of extracellular
      volume, which is defined as the effective arterial blood volume (EABV), is to
      ensure adequate perfusion of cells and organs. Other factors, including cardiac
      output, total and regional capacity of both arteries and veins, Starling forces
      in the capillaries, and gravity also affect the EABV. Collectively, these factors
      interact closely with extracellular volume and some of them undergo substantial
      changes in certain acute and chronic severe illnesses. Their changes result not
      only in extracellular volume expansion, but in the need for a larger
      extracellular volume compared with that of healthy individuals. Assessing
      extracellular volume in severe illness is challenging because the estimates of
      this volume by commonly used methods are prone to large errors in many illnesses.
      In addition, the optimal extracellular volume may vary from illness to illness,
      is only partially based on volume measurements by traditional methods, and has
      not been determined for each illness. Further research is needed to determine
      optimal extracellular volume levels in several illnesses. For these reasons,
      extracellular volume in severe illness merits a separate third concept of body
      fluid balance.

PMID- 29359122
TI  - Alpha Thalassemia/Mental Retardation Syndrome X-Linked, the Alternative
      Lengthening of Telomere Phenotype, and Gliomagenesis: Current Understandings and
      Future Potential.
AB  - Gliomas are the most common primary malignant brain tumor in humans. Lower grade
      gliomas are usually less aggressive but many cases eventually progress to a more
      aggressive secondary glioblastoma (GBM, WHO Grade IV), which has a universally
      fatal prognosis despite maximal surgical resection and concurrent chemo
      radiation. With the identification of molecular markers, however, there is
      promise for improving diagnostic and therapeutic strategies. One of the key
      molecular alterations in gliomas is the alpha thalassemia/mental retardation
      syndrome X-linked (ATRX) gene, which is frequently mutated. One-third of
      pediatric GBM cases are also found to have the ATRX mutation and the genetic
      signatures are different from adult cases. The exact role of ATRX mutations in
      gliomagenesis, however, is unclear. In this review, we describe the normal
      cellular function of the ATRX gene product followed by consequences of its
      dysfunction. Furthermore, its possible association with the alternative
      lengthening of telomeres (ALT) phenotype is outlined. Lastly, therapeutic options
      potentiated through a better understanding of ATRX and the ALT phenotype are
      explored.

PMID- 29359123
TI  - Plasma Lipidomic Signature of Rectal Adenocarcinoma Reveals Potential Biomarkers.
AB  - Background: Rectal adenocarcinoma (RAC) is a common malignant tumor of the
      digestive tract and survival is highly dependent upon stage of disease at
      diagnosis. Lipidomic strategy can be used to identify potential biomarkers for
      establishing early diagnosis or therapeutic programs for RAC. Objective: To
      evaluate the lipoperoxidation biomarkers and lipidomic signature in the plasma of
      patients with RAC (n = 23) and healthy controls (n = 18). Methods:
      Lipoperoxidation was evaluated based on malondialdehyde (MDA) and F2-isoprostane
      levels and the lipidomic profile obtained by gas chromatography and high
      resolution mass spectrometry (ESI-q-TOF) associated with a multivariate
      statistical technique. Results: The most abundant ions identified in the RAC
      patients were those of protonated phosphatidylcholine and
      phosphatidylethanolamine. It was found that a lisophosphatidylcholine (LPC)
      plasmalogen containing palmitoleic acid [LPC (P-16:1)], with highest variable
      importance projection score, showed a tendency to be lower in the cancer
      patients. A reduction of n - 3 polyunsaturated fatty acids was observed in the
      plasma of these patients. MDA levels were higher in patients with advanced cancer
      (stages III/IV) than in the early stages groups and the healthy group (p < 0.05).
      No differences in F2-isoprostane levels were observed among these groups.
      Conclusion: This study shows that the reduction in plasma levels of LPC
      plasmalogens associated with an increase in MDA levels may indicate increased
      oxidative stress in these patients and identify the metabolite LPC (P-16:1) as a
      putatively novel lipid signature for RAC.

PMID- 29359125
TI  - The Journal of Comorbidity affiliates with the Scottish School of Primary Care.

PMID- 29359124
TI  - Perceived value of eHealth among people living with multimorbidity: a qualitative
      study.
AB  - Background: The prevalence of multimorbidity is increasing, creating challenges
      for patients, healthcare professionals, and healthcare systems. Given that
      chronic disease management increasingly involves eHealth, it is useful to assess
      its perceived value among people with multimorbidity. Objective: To explore
      challenges related to multimorbidity and patients' perspectives on eHealth.
      Design: Ten semi-structured interviews with adults, living with multimorbidity in
      Copenhagen, Denmark. Interviews focused on patient-experienced challenges, from
      challenges related to self-management to challenges experienced in the healthcare
      sector, as well as perceptions of eHealth. During interviews, participants were
      presented with pictures of different eHealth technologies. Data analysis followed
      the systematic text condensation approach. Results: Participants experienced
      challenges in their daily lives, e.g. when practicing self-management activities,
      when navigating the healthcare sector, and when interacting with healthcare
      professionals. Patient-perceived value of eHealth varied, depending on their
      burden of illness and treatment: those with a greater burden had more positive
      perceptions of eHealth, and expressed more intention to use it. Participants with
      less complex disease patterns and less burdensome treatment regimens were more
      likely to perceive eHealth as something worthless and undesirable. Participants
      stressed that eHealth should only be introduced as an optional supplement.
      Conclusions: eHealth can potentially address some patient-experienced challenges
      related to multimorbidity by promoting self-management, patient-centeredness, and
      access. However, patients' needs and preferences vary and eHealth cannot
      substitute the personal interaction between patient and healthcare professionals.
      Our findings point to the importance of patient assessment and stratification to
      ensure appropriate use of eHealth.

PMID- 29359126
TI  - The Price per Prospective Consumer of Providing Therapist Training and
      Consultation in Seven Evidence-Based Treatments within a Large Public Behavioral
      Health System: An Example Cost-Analysis Metric.
AB  - Objective: Public-sector behavioral health systems seeking to implement evidence
      based treatments (EBTs) may face challenges selecting EBTs given their limited
      resources. This study describes and illustrates one method to calculate cost
      related to training and consultation to assist system-level decisions about which
      EBTs to select. Methods: Training, consultation, and indirect labor costs were
      calculated for seven commonly implemented EBTs. Using extant literature, we then
      estimated the diagnoses and populations for which each EBT was indicated.
      Diagnostic and demographic information from Medicaid claims data were obtained
      from a large behavioral health payer organization and used to estimate the number
      of covered people with whom the EBT could be used and to calculate implementation
      associated costs per consumer. Results: Findings suggest substantial cost to
      therapists and service systems related to EBT training and consultation. Training
      and consultation costs varied by EBT, from Dialectical Behavior Therapy at
      $238.07 to Cognitive Behavioral Therapy at $0.18 per potential consumer served.
      Total cost did not correspond with the number of prospective consumers served by
      an EBT. Conclusion: A cost-metric that accounts for the prospective recipients of
      a given EBT within a given population may provide insight into how systems should
      prioritize training efforts. Future policy should consider the financial burden
      of EBT implementation in relation to the context of the population being served
      and begin a dialog in creating incentives for EBT use.

PMID- 29359128
TI  - Virtual Reality-Based Center of Mass-Assisted Personalized Balance Training
      System.
AB  - Poststroke hemiplegic patients often show altered weight distribution with
      balance disorders, increasing their risk of fall. Conventional balance training,
      though powerful, suffers from scarcity of trained therapists, frequent visits to
      clinics to get therapy, one-on-one therapy sessions, and monotony of repetitive
      exercise tasks. Thus, technology-assisted balance rehabilitation can be an
      alternative solution. Here, we chose virtual reality as a technology-based
      platform to develop motivating balance tasks. This platform was augmented with
      off-the-shelf available sensors such as Nintendo Wii balance board and Kinect to
      estimate one's center of mass (CoM). The virtual reality-based CoM-assisted
      balance tasks (Virtual CoMBaT) was designed to be adaptive to one's
      individualized weight-shifting capability quantified through CoM displacement.
      Participants were asked to interact with Virtual CoMBaT that offered tasks of
      varying challenge levels while adhering to ankle strategy for weight shifting. To
      facilitate the patients to use ankle strategy during weight-shifting, we designed
      a heel lift detection module. A usability study was carried out with 12
      hemiplegic patients. Results indicate the potential of our system to contribute
      to improving one's overall performance in balance-related tasks belonging to
      different difficulty levels.

PMID- 29359127
TI  - Genetic Mapping of Quantitative Trait Loci for Grain Yield under Drought in Rice
      under Controlled Greenhouse Conditions.
AB  - Drought stress is a constant threat to rice production worldwide. Most modern
      rice cultivars are sensitive to drought, and the effect is severe at the
      reproductive stage. Conventional breeding for drought resistant (DR) rice
      varieties is slow and limited due to the quantitative nature of the DR traits.
      Identification of genes (QTLs)/markers associated with DR traits is a
      prerequisite for marker-assisted breeding. Grain yield is the most important
      trait and to this end drought yield QTLs have been identified under field
      conditions. The present study reports identification of drought yield QTLs under
      controlled conditions without confounding effects of other factors prevalent
      under natural conditions. A linkage map covering 1,781.5 cM with an average
      resolution of 9.76 cM was constructed using an F2 population from a cross between
      two Japonica cultivars, Cocodrie (drought sensitive) and Vandana (drought
      tolerant) with 213 markers distributed over 12 rice chromosomes. A subset of 59
      markers (22 genic SSRs and 37 SNPs) derived from the transcriptome of the parents
      were also placed in the map. Single marker analysis using 187 F2 : 3 progeny
      identified 6 markers distributed on chromosomes 1, 5, and 8 to be associated with
      grain yield under drought (GYD). Composite interval mapping identified six
      genomic regions/quantitative trait loci (QTL) on chromosome 1, 5, 8, and 9 to be
      associated with GYD. QTLs located on chromosome 1 (qGYD1.2, qGYD1.3), chromosome
      5 (qGYD5.1) and chromosome 8 (qGYD8.1) were contributed by Vandana alleles,
      whereas the QTLs, qGYD1.1 and qQYD9.1 were contributed by Cocodrie alelles. The
      additive positive phenotypic variance explained by the QTLs ranged from 30.0 to
      34.0%. Candidate genes annotation within QTLs suggested the role of transcription
      factors and genes involved in osmotic potential regulation through
      catalytic/metabolic pathways in drought tolerance mechanism contributing to
      yield.

PMID- 29359129
TI  - Mitochondrial Tethers and Their Impact on Lifespan in Budding Yeast.
AB  - Tethers that link mitochondria to other organelles are critical for lipid and
      calcium transport as well as mitochondrial genome replication and fission of the
      organelle. Here, we review recent advances in the characterization of
      interorganellar mitochondrial tethers in the budding yeast, Saccharomyces
      cerevisiae. We specifically focus on evidence for a role for mitochondrial
      tethers that anchor mitochondria to specific regions within yeast cells. These
      tethering events contribute to two processes that are critical for normal
      replicative lifespan: inheritance of fitter mitochondria by daughter cells, and
      retention of a small pool of higher-functioning mitochondria in mother cells.
      Since asymmetric inheritance of mitochondria also occurs in human mammary stem
      like cells, it is possible that mechanisms underlying mitochondrial segregation
      in yeast also operate in other cell types.

PMID- 29359130
TI  - Techniques for Non-Invasive Monitoring of Arterial Blood Pressure.
AB  - Since both, hypotension and hypertension, can potentially impair the function of
      vital organs such as heart, brain, or kidneys, monitoring of arterial blood
      pressure (BP) is a mainstay of hemodynamic monitoring in acutely or critically
      ill patients. Arterial BP can either be obtained invasively via an arterial
      catheter or non-invasively. Non-invasive BP measurement provides either
      intermittent or continuous readings. Most commonly, an occluding upper arm cuff
      is used for intermittent non-invasive monitoring. BP values are then obtained
      either manually (by auscultation of Korotkoff sounds or palpation) or
      automatically (e.g., by oscillometry). For continuous non-invasive BP monitoring,
      the volume clamp method or arterial applanation tonometry can be used. Both
      techniques enable the arterial waveform and BP values to be obtained
      continuously. This article describes the different techniques for non-invasive BP
      measurement, their advantages and limitations, and their clinical applicability.

PMID- 29359132
TI  - Anesthetic Management for Multiple Family Members with Myotonic Dystrophy for
      Interventional Cardiac Procedures-A Case Series.
AB  - Myotonic muscular dystrophy (MMD) is a rare autosomal dominant disorder that can
      complicate anesthetic management of patients. MMD is characterized by
      progressively worsening muscle loss and weakness, cardiac conduction
      abnormalities, cardiomyopathy, restrictive lung disease, obstructive sleep apnea,
      and delayed gastric emptying. Patients presenting with MMD for any surgical
      procedure present a management challenge to the anesthesiologist. Several reports
      of airway loss due to medication-mediated respiratory depression, sudden death
      due to dysrhythmias, aspiration of stomach contents, and prolonged intubation
      have been reported. We present a case series of three family members with MMD
      type 1 who presented for electrophysiologic assessment of the cardiac conduction
      system and possible pacemaker insertion. While there are reports of anesthetic
      management of patients with myotonic dystrophy for various procedures, our report
      is unique in that we were able to demonstrate variations of anesthetic management
      based on the procedure and variation in disease phenotype-differing severity
      between family members.

PMID- 29359131
TI  - Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity
      during and after Pregnancy.
AB  - Symptoms of rheumatoid arthritis (RA) improve during pregnancy, a phenomenon that
      was found to be associated with N-glycosylation changes of immunoglobulin G.
      Recent advances in high-throughput glycosylation analysis allow the assessment of
      the N-glycome of human sera as well. The aim of this study was to identify new
      protein N-glycosylation properties that associate with changes in RA disease
      activity during and after pregnancy. A longitudinal cohort of serum samples was
      collected during 285 pregnancies (32 control individuals and 253 RA patients).
      Per individual one sample was collected before conception, three during
      pregnancy, and three after delivery. Released serum protein N-glycans were
      measured by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF-MS) after employing chemical modification of the sialic
      acids to allow discrimination of sialic acid linkage isomers. Serum protein N
      glycosylation showed strongly modified during pregnancy, with similar changes
      visible in control individuals and RA pregnancies. Namely, a decrease in
      bisection and an increase in galactosylation in diantennary glycans were found,
      as well as an increase in tri- and tetraantennary species and alpha2,3-linked
      sialylation thereof. The change in RA disease activity [DAS28(3)-CRP] proved
      negatively associated with the galactosylation of diantennary N-glycans, and
      positively with the sialylation of triantennary fucosylated species (A3FGS).
      While the protein source of the novel finding A3FGS is thus far unknown, its
      further study may improve our understanding of the etiology of RA disease
      severity.

PMID- 29359133
TI  - De novo Assembly and Annotation of the Antarctic Alga Prasiola crispa
      Transcriptome.

PMID- 29359134
TI  - Staff Recall Travel Time for ST Elevation Myocardial Infarction Impacted by
      Traffic Congestion and Distance: A Digitally Integrated Map Software Study.
AB  - Background: Recent evidence suggests hospitals fail to meet guideline specified
      time to percutaneous coronary intervention (PCI) for a proportion of ST elevation
      myocardial infarction (STEMI) presentations. Implicit in achieving this time is
      the rapid assembly of crucial catheter laboratory staff. As a proof-of-concept,
      we set out to create regional maps that graphically show the impact of traffic
      congestion and distance to destination on staff recall travel times for STEMI,
      thereby producing a resource that could be used by staff to improve reperfusion
      time for STEMI. Methods: Travel times for staff recalled to one inner and one
      outer metropolitan hospital at midnight, 6 p.m., and 7 a.m. were estimated using
      Google Maps Application Programming Interface. Computer modeling predictions were
      overlaid on metropolitan maps showing color coded staff recall travel times for
      STEMI, occurring within non-peak and peak hour traffic congestion times. Results:
      Inner metropolitan hospital staff recall travel times were more affected by
      traffic congestion compared with outer metropolitan times, and the latter was
      more affected by distance. The estimated mean travel times to hospital during
      peak hour were greater than midnight travel times by 13.4 min to the inner and
      6.0 min to the outer metropolitan hospital at 6 p.m. (p < 0.001). At 7 a.m., the
      mean difference was 9.5 min to the inner and 3.6 min to the outer metropolitan
      hospital (p < 0.001). Only 45% of inner metropolitan staff were predicted to
      arrive within 30 min at 6 p.m. compared with 100% at midnight (p < 0.001), and
      56% of outer metropolitan staff at 6 p.m. (p = 0.021). Conclusion: Our results
      show that integration of map software with traffic congestion data, distance to
      destination and travel time can predict optimal residence of staff when on-call
      for PCI.

PMID- 29359136
TI  - Integrin alpha7: a major driver and therapeutic target for glioblastoma
      malignancy.

PMID- 29359138
TI  - Not just another biomarker: the role of integrin alpha 7 in glioblastoma.

PMID- 29359137
TI  - Extracellular vesicles and aging.
AB  - Aging and the chronic diseases associated with aging place a tremendous burden on
      our healthcare system. As our world population ages dramatically over the next
      decades, this will only increase. Hence, there is a great need to discover
      fundamental mechanisms of aging to enable development of strategies for
      minimizing the impact of aging on our health and economy. There is general
      agreement that cell autonomous mechanisms contribute to aging. As cells accrue
      damage over time, they respond to it by triggering individual cell fate decisions
      that ultimately disrupt tissue homeostasis and thus increase risk of morbidity.
      However, there are numerous lines of evidence, including heterochronic parabiosis
      and plasma transfer, indicating that cell non-autonomous mechanisms are
      critically important for aging as well. In addition, senescent cells, which
      accumulate in tissues with age, can display a senescence-associated secretory
      phenotype (SASP) that contributes to driving aging and loss of tissue homeostasis
      through a non-cell autonomous mechanism(s). Given the diverse roles of blood
      borne extracellular vesicles (EVs) in modulating not only the immune response,
      but also angiogenesis and tissue regeneration, they likely play a key role in
      modulating the aging process through cell non-autonomous mechanisms. The fact
      that senescent cells release more EVs and with a different composition suggests
      they contribute to the adverse effects of senescence on aging. In addition, the
      ability of EVs from functional progenitor cells to promote tissue regeneration
      suggests that stem cell-derived EVs could be used therapeutically to extend
      healthspan. This review focuses on the potential roles of EVs in aging, the
      potential of EV-based therapeutic applications for extending healthspan and the
      potential for use of circulating EVs as biomarkers of unhealthy aging.

PMID- 29359135
TI  - Antimicrobial Resistance: Its Surveillance, Impact, and Alternative Management
      Strategies in Dairy Animals.
AB  - Antimicrobial resistance (AMR), one among the most common priority areas
      identified by both national and international agencies, is mushrooming as a
      silent pandemic. The advancement in public health care through introduction of
      antibiotics against infectious agents is now being threatened by global
      development of multidrug-resistant strains. These strains are product of both
      continuous evolution and un-checked antimicrobial usage (AMU). Though antibiotic
      application in livestock has largely contributed toward health and productivity,
      it has also played significant role in evolution of resistant strains. Although,
      a significant emphasis has been given to AMR in humans, trends in animals, on
      other hand, are not much emphasized. Dairy farming involves surplus use of
      antibiotics as prophylactic and growth promoting agents. This non-therapeutic
      application of antibiotics, their dosage, and withdrawal period needs to be re
      evaluated and rationally defined. A dairy animal also poses a serious risk of
      transmission of resistant strains to humans and environment. Outlining the scope
      of the problem is necessary for formulating and monitoring an active response to
      AMR. Effective and commendably connected surveillance programs at
      multidisciplinary level can contribute to better understand and minimize the
      emergence of resistance. Besides, it requires a renewed emphasis on investments
      into research for finding alternate, safe, cost effective, and innovative
      strategies, parallel to discovery of new antibiotics. Nevertheless, numerous
      direct or indirect novel approaches based on host-microbial interaction and
      molecular mechanisms of pathogens are also being developed and corroborated by
      researchers to combat the threat of resistance. This review places a concerted
      effort to club the current outline of AMU and AMR in dairy animals; ongoing
      global surveillance and monitoring programs; its impact at animal human
      interface; and strategies for combating resistance with an extensive overview on
      possible alternates to current day antibiotics that could be implemented in
      livestock sector.

PMID- 29359139
TI  - Acute myeloid leukemia and fatal Scedosporium prolificans sepsis after eculizumab
      treatment for paroxysmal nocturnal hemoglobinuria: a case report.
AB  - Eculizumab has become the standard of care for patients with paroxysmal nocturnal
      hemoglobinuria (PNH). As more patients are treated, the long-term outcomes of
      these patients will become apparent. We recently treated a patient who developed
      PNH in the setting of aplastic anemia. The patient developed acute myeloid
      leukemia less than three years after initiating eculizumab. The patient also died
      suddenly from Scedosporium sepsis during induction therapy. This patient's course
      seemed more aggressive than would be expected. The possible effect of complement
      blockade is discussed.

PMID- 29359140
TI  - Human induced pluripotent stem cell-derived neuronal progenitors are a suitable
      and effective drug discovery model for neurological mtDNA disorders.

PMID- 29359141
TI  - Extracellular vesicles and cardiovascular disease therapy.
AB  - Cardiovascular disease (CVD) constitutes one of the leading causes of mortality
      worldwide, therefore representing a major public health concern. Despite recent
      advances in the treatment of patients with acute myocardial infarction (AMI),
      such as bypass surgery or percutaneous coronary intervention, pathological
      cardiac remodeling often predisposes survivors to fatal heart failure. In this
      context, the proven efficacy of stem cell-regenerative therapies constitutes a
      promising therapeutic perspective with is nevertheless slow down by safety and
      ethical concerns. Recent studies have underscored the capacity of stem cell
      derived extracellular vesicles (EV) to recapitulate the regenerative properties
      of their parental cells therefore offering a therapeutic alternative to cell
      therapy in cardiovascular regenerative medicine. In this article, we review the
      functional relevance of using stem cell-derived EV as therapeutically agents and
      detail the identified molecular pathways that they used to exert their effects.
      We also discuss the advantages of using such an acellular regenerative therapy,
      in regard with parental stem cells, and address the limitations, which would need
      to be resolved, before their clinical translation.

PMID- 29359142
TI  - Evaluation of Two Supplemented Culture Media for Long-Term, Room-Temperature
      Preservation of Streptococcus pneumoniae Strains.
AB  - Objective: To produce two supplemented agar types in order to store pneumococci
      for several months at room temperature. Methods: Todd
      Hewitt/Hemoglobin/Yeast/Charcoal/Agar (TH-HYC) and Todd-Hewitt/Skim
      Milk/Yeast/Charcoal/Agar (TH-SYC) were used to prepare two supplemented agar
      types. Nineteen pneumococci isolated from patients or asymptomatic carriers
      displaying diverse serotypes and multilocus sequence types (MLST) were
      subcultured and stored onto supplemented agar types, in four different tests, at
      room temperature. Findings: At the end of all tests (4-6 months) all
      noncontaminated subcultures were viable and maintained all phenotypic
      characteristics. Survival-time curves revealed a slow decrease of viable CFU over
      time on agar types, but at the end the number of viable CFU was satisfactory
      (>=2+ of growth). Decreasing of CFU was significantly higher for clinical versus
      nasopharyngeal isolates. Subcultures contamination rates were 6.25% and 14.58%
      after 2 and 6 months of storage, respectively. Conclusion: TH-HYC and TH-SYC agar
      types allowed the viability of pneumococci with several serotypes, MLST, and
      genetic profiles, after 6 months of storage at room temperature. We consider that
      these agar types are a valid alternative to preserve pneumococci over an extended
      period, especially when methods as cryopreservation or lyophilization are not
      available, and are useful for transporting strains between laboratories.

PMID- 29359143
TI  - Dexmedetomidine Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury by
      Suppressing TLR4-MyD88-NF-kappaB Signaling.
AB  - Objective: We previously reported that dexmedetomidine (DEX) offers
      cardioprotection against ischemia/reperfusion injury in rats. Here, we evaluated
      the role of toll-like receptors 4- (TLR4-) myeloid differentiation primary
      response 88- (MyD88-) nuclear factor-kappa B (NF-kappaB) signaling in DEX
      mediated protection of cardiomyocytes using in vitro models of
      hypoxia/reoxygenation (H/R). Methods: The experiments were carried out in H9C2
      cells and in primary neonatal rat cardiomyocytes. Cells pretreated with vehicle
      or DEX were exposed to hypoxia for 1 h followed by reoxygenation for 12 h. We
      analyzed cell viability and lactate dehydrogenase (LDH) activity and measured
      tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1beta mRNA
      levels, TLR4, MyD88, and nuclear NF-kappaB p65 protein expression and NF-kappaB
      p65 nuclear localization. TLR4 knock-down by TLR4 siRNA transfection and
      overexpression by TLR4 DNA transfection were used to further confirm our
      findings. Results: DEX protected against H/R-induced cell damage and
      inflammation, as evidenced by increased cell survival rates, decreased LDH
      activity, and decreased TNF-alpha, IL-6, and IL-1beta mRNA levels, as well as
      TLR4 and NF-kappaB protein expression. TLR4 knock-down partially prevented cell
      damage following H/R injury, while overexpression of TLR4 abolished the DEX
      mediated protective effects. Conclusions: DEX pretreatment protects rat
      cardiomyocytes against H/R injury. This effect is partly mediated by TLR4
      suppression via TLR4-MyD88-NF-kappaB signaling.

PMID- 29359144
TI  - Respiratory Tract Viral Infections and Coinfections Identified by AnyplexTM II
      RV16 Detection Kit in Pediatric Patients at a Riyadh Tertiary Care Hospital.
AB  - Respiratory infections are caused by an array of viruses, and limited information
      is available about viral coexistence, comparative symptoms, and the burden of
      illness. This retrospective cohort study aimed to determine the etiological
      agents responsible for respiratory tract infections by Anyplex II RV16 detection
      kit (RV16, Seegene), involving 2266 pediatric patients with respiratory
      infections admitted to the Department of Pediatrics at King Abdul-Aziz Medical
      City, Ministry of National Guard, Riyadh, from July 2014 to June 2015. The most
      frequent respiratory infections were recorded in the 1 to 5 year age group
      (44.7%). Rhinovirus (32.5%), Adenovirus (16.9%), and Respiratory syncytial virus
      (RSV) B (10.4%) were most common. In single viral infections, Rhinovirus (41.2%),
      Metapneumovirus (15.3%), and Bocavirus (13.7%) were most frequent. In multiple
      viral infections, Rhinovirus (36.7%), Adenovirus (35.2%), Bocavirus (11.2), RSV B
      (7.8%), and RSV A (6.7%) were most frequent. No significant difference was
      observed in clinical presentations; however, rhinorrhea and hypodynamia were
      significantly associated with viral respiratory infections. Most respiratory
      viral pathogens peaked during December, January, March, and April. Rhinovirus,
      Adenovirus, and Bocavirus circulations were detected throughout the year. Winter
      peaks were recorded for Rhinovirus, RSV B, Adenovirus, and RSV A, whereas the
      Metapneumovirus, and the Bocavirus peaked in March and April. These findings
      enhance understanding of viral etiology and distribution to improve respiratory
      infection management and treatment.

PMID- 29359145
TI  - Immune Response and Protective Efficacy of a Heterologous DNA-Protein
      Immunization with Leishmania Superoxide Dismutase B1.
AB  - Growing evidence shows that antioxidant proteins of Leishmania could be used as
      vaccine candidates. In this study, we report the efficacy of Leishmania donovani
      iron superoxide dismutase B1 (LdFeSODB1) as a vaccine antigen in BALB/c mice in a
      DNA-protein prime-boost immunization regimen in the presence or absence of murine
      granulocyte macrophage colony stimulating factor (mGMCSF) DNA adjuvant. The
      expression study confirmed that LdFeSODB1 is expressed in mammalian cells and
      mGMCSF fusion mediates the secretion of the recombinant protein. Heterologous
      immunization with LdFeSODB1 induced a strong antibody- and cell-mediated immune
      response in mice. Immunization triggered a mixed Th1/Th2 response as evidenced by
      the ratio of IgG2a to IgG1. Antigen-stimulated spleen cells from the immunized
      mice produced high level IFN-gamma. Multiparametric flow cytometry data showed
      that immunization with LdFeSODB1 induced significantly higher expression of TNF
      alpha or IL-2 by antigen-stimulated T cells. Eight weeks after L. major
      infection, immunization with the antigen shifted the immune response to a more
      Th1 type than the controls as demonstrated by IgG2a/IgG1 ratio. Moreover, IFN
      gamma production by antigen-stimulated spleen cells from immunized mice remained
      high. The footpad swelling experiment showed that immunization with LdFeSODB1
      resulted in partial protection of mice from a high dose L. major infection.

PMID- 29359146
TI  - Prospective Validation of the Decalogue, a Set of Doctor-Patient Communication
      Recommendations to Improve Patient Illness Experience and Mood States within a
      Hospital Cardiologic Ambulatory Setting.
AB  - Strategies to improve doctor-patient communication may have a beneficial impact
      on patient's illness experience and mood, with potential favorable clinical
      effects. We prospectively tested the psychometric and clinical validity of the
      Decalogue, a tool utilizing 10 communication recommendations for patients and
      physicians. The Decalogue was administered to 100 consecutive patients referred
      for a cardiologic consultation, whereas 49 patients served as controls. The POMS
      2 questionnaire was used to measure the total mood disturbance at the end of the
      consultation. Structural equation modeling showed high internal consistency
      (Cronbach alpha 0.93), good test-retest reproducibility, and high validity of the
      psychometric construct (all > 0.80), suggesting a positive effect on patients'
      illness experience. The total mood disturbance was lower in the patients exposed
      to the Decalogue as compared to the controls (1.4 +/- 12.1 versus 14.8 +/- 27.6,
      p = 0.0010). In an additional questionnaire, patients in the Decalogue group
      showed a trend towards a better understanding of their state of health (p =
      0.07). In a cardiologic ambulatory setting, the Decalogue shows good validity and
      reliability as a tool to improve patients' illness experience and could have a
      favorable impact on mood states. These effects might potentially improve patient
      engagement in care and adherence to therapy, as well as clinical outcome.

PMID- 29359148
TI  - Growth Abnormalities of Fetuses and Infants.

PMID- 29359147
TI  - Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Avenues.

PMID- 29359149
TI  - Isolation of Potential Phages against Multidrug-Resistant Bacterial Isolates:
      Promising Agents in the Rivers of Kathmandu, Nepal.
AB  - Bacteriophages are being the subject of interest for alternative antimicrobial
      therapy for infectious diseases in recent years. Therapeutic effectiveness
      regarding phage therapy is a matter of concern since it is the most promising
      biological treatment of this era. Hence, the present study was aimed to isolate
      the potential bacteriophages present in river water samples and to analyze their
      host range among clinical strains of bacteria. Ten different locations of
      Kathmandu valley were selected for the collection of river water for the
      detection of probable phages. Bacteriophages were isolated from water samples
      using the double agar overlay method. Isolated phages were purified by diluting
      in the SM-buffer and filtering through 0.22 MUm filter. Purified lysate was
      further processed for analyzing its host range by using spot method. Their host
      range was characterized against 20 bacterial strains, including multidrug
      resistant. Total 67 different phages were isolated against 8 different host
      organisms. Out of them, forty-seven phages were selected for analyzing its host
      range. Among them, Serratia phages (PhiSER) had the broad host range infecting 17
      different bacterial strains including multidrug-resistant harboring ESBL and MBL
      genotypes. However, Klebsiella phages (PhiKP) had narrow host range in comparison
      to other phages. Isolated phages had the potential effect against clinical
      strains of bacteria along with their broader host spectrum. Most importantly,
      promising effect against MDR pathogens in this study has raised the probable
      chances of the utility of these phages for biological control of bacterial
      infection including MBL and ESBL strains.

PMID- 29359150
TI  - Microcystins Presence in Mussels (M. galloprovincialis) and Water of Two
      Productive Mediterranean's Lagoons (Sardinia, Italy).
AB  - Microcystins (MCs) are hepatotoxins harmful for animal and human health. The most
      toxic type between them is MC-LR whose presence has been investigated in
      different reservoirs all around the world. In this work microcystins were
      monitored in spring and summer in water and mussels (Mytilus galloprovincialis)
      of two Sardinia lagoons: Cabras and Calich lagoons. A Solid Phase Extraction
      method was developed to clean and concentrate samples before the Enzyme Linked
      Immunosorbent Assay (ELISA) and the following Mass Spectrometry detection. MCs
      presence was detected using the screening ELISA test in both lagoons. MCs peak
      was revealed in July for water and mussels belonging to Cabras lagoon (0.75 +/-
      0.07 ng/L in water and 0.12 +/- 0.04 ng/g ww in mussels). In water of Calich
      lagoon there was a constant trend in the concentration of MCs during the
      considered months, while there was a MCs peak in July (0.6 +/- 0.5 ng/g ww) in
      mussels. The following LC-MS/MS analysis did not reveal MC-LR presence in all
      analyzed samples. These results can be useful to enrich knowledge on public
      health and consumer's safeguard.

PMID- 29359151
TI  - A Randomized Comparison of Bougie-Assisted and TracheoQuick Plus Cricothyrotomies
      on a Live Porcine Model.
AB  - Objectives: Cricothyrotomy is a rescue procedure in "cannot intubate, cannot
      oxygenate" scenarios where other methods of nonsurgical airway management have
      failed. We compared 2 cuffed cricothyrotomy sets, bougie-assisted cricothyrotomy
      (BACT) and novel percutaneous TracheoQuick Plus, on a live porcine model in a
      simulated periarrest situation. Methods: Thirty-four anesthetized minipigs were
      randomly allocated into two groups: BACT technique (n = 17) and TracheoQuick Plus
      (n = 17). The primary outcome was duration of cricothyrotomy while secondary
      outcomes were total success rate, number of attempts, location of incision,
      changes in heart rate, oxygen saturation, and the incidence of complications.
      Results: BACT was significantly faster than TracheoQuick Plus cricothyrotomy,
      with a median time of 69 sec (IQR 56-85) versus 178 sec (IQR 152-272). The total
      success rate was without difference. 94% of BACT was performed successfully on
      the first attempt, while in the TracheoQuick Plus group, it was only 18% (P <
      0.001). Trauma to the posterior tracheal wall was observed once in the BACT group
      and 5 times in the TracheoQuick Plus group. Oxygen saturation was significantly
      higher in the BACT group both during and after the procedure. Conclusions: BACT
      is superior to TracheoQuick Plus cricothyrotomy on a live animal model.

PMID- 29359152
TI  - Corrigendum to "Molecular Cloning, Bioinformatic Analysis, and Expression of
      Bombyx mori Lebocin 5 Gene Related to Beauveria bassiana Infection".
AB  - [This corrects the article DOI: 10.1155/2017/9390803.].

PMID- 29359153
TI  - Morphological Asymmetry of the Superior Cervical Facets from C3 through C7 due to
      Degeneration.
AB  - Introduction: Knowledge about facet morphology has already been discussed
      extensively in literature but is limited regarding asymmetry and its relation to
      facet degeneration. Method: Facet dimensions, surface area, curvature, and
      degeneration of the superior facets were measured in 85 dried human vertebrae
      from the anatomical collection of the Vrije Universiteit Brussel. The vertebrae
      were analysed using the Microscribe G2X digitizer (Immersion Co., San Jose, CA)
      and a grading system for the evaluation of cervical facet degeneration.
      Coordinates were processed mathematically to evaluate articular tropism. The
      statistical analysis includes the paired t-test and the Pearson correlation.
      Results: On average, no systematic differences between the left and right facets
      were found concerning morphology and degeneration. However, there were
      significant differences regardless of the side-occurrence. There was a
      significant correlation between the dimensions of the total facet surface and the
      degree of degeneration but not for the recognizable joint surface. Conclusions:
      Facet tropism of the upper joint facets occurred often in the cervical spine but
      without side preference. A bigger difference in degeneration asymmetry was
      associated with a bigger difference in facet joint dimension asymmetry.

PMID- 29359154
TI  - Red Cell Distribution Width Is Associated with All-Cause and Cardiovascular
      Mortality in Patients with Diabetes.
AB  - Background and Methods: Red cell distribution width (RDW) has emerged as a
      prognostic marker in patients with cardiovascular diseases. We investigated
      mortality in patients with diabetes included in the National Health and Nutrition
      Examination Survey, in relation to baseline RDW. RDW was divided into 4 quartiles
      (Q1: <=12.4%, Q2: 12.5%-12.9%, Q3: 13.0%-13.7%, and Q4: >13.7%). Results: A total
      of 3,061 patients were included: mean age 61 +/- 14 years, 50% male, 39% White.
      Mean RDW was 13.2% +/- 1.4%. Compared with first quartile (Q1) of RDW, patients
      in Q4 were more likely to be older, female, and African-American, have had
      history of stroke, myocardial infarction, and heart failure, and have chronic
      kidney disease. After a median follow-up of 6 years, 628 patient died (29% of
      cardiovascular disease). Compared with Q1, patients in Q4 were at increased risk
      for all-cause mortality (HR 3.44 [2.74-4.32], P < .001) and cardiovascular
      mortality (HR 3.34 [2.16-5.17], P < .001). After adjusting for 17 covariates, RDW
      in Q4 remained significantly associated with all-cause mortality (HR 2.39 [1.30
      4.38], P = 0.005) and cardiovascular mortality (HR 1.99 [1.17-3.37], P = 0.011).
      Conclusion: RDW is a powerful and an independent marker for prediction of all
      cause mortality and cardiovascular mortality in patients with diabetes.

PMID- 29359156
TI  - Genome-Wide Analysis of mRNA and Long Noncoding RNA Profiles in Chronic Actinic
      Dermatitis.
AB  - Chronic actinic dermatitis (CAD), a photosensitive dermatosis, is characterized
      by inflammatory lesions, especially on sun-exposed skin. However, its
      pathogenesis remains unclear. In this study, second-generation RNA sequencing and
      comprehensive bioinformatics analyses of mRNAs and long noncoding RNAs (lncRNAs)
      were performed to determine the transcriptome profiles of patients with CAD. A
      total 6889 annotated lncRNAs, 341 novel lncRNAs, and 65091 mRNAs were identified.
      Interestingly, patients with CAD and healthy controls showed distinct
      transcriptome profiles. Indeed, 198 annotated (81.48%) and 45 novel (18.52%)
      lncRNAs were differentially expressed between the two groups. GO, KEGG, and RGSEA
      analyses of lncRNAs showed that inflammatory and immune response related pathways
      played crucial roles in the pathogenetic mechanism of CAD. In addition, we
      unveiled key differentially expressed lncRNAs, including lncRNA RP11-356I2.4
      which plays a role probably by regulating TNFAIP3 and inflammation. qRT-PCR data
      validated the differentially expressed genes. The newly identified lncRNAs may
      have potential roles in the development of CAD; these findings lay a solid
      foundation for subsequent functional exploration of lncRNAs and mRNAs as
      therapeutic targets for CAD.

PMID- 29359157
TI  - Analysis of a New Delayed HBV Model with Exposed State and Immune Response to
      Infected Cells and Viruses.
AB  - We propose a comprehensive delayed HBV model, which not only considers the immune
      response to both infected cells and viruses and a time delay for the immune
      system to clear viruses but also incorporates an exposed state and the
      proliferation of hepatocytes. We prove the positivity and boundedness of
      solutions and analyze the global stability of two boundary equilibria and then
      study the local asymptotic stability and Hopf bifurcation of the positive
      (infection) equilibrium and also the stability of the bifurcating periodic
      solutions. Moreover, we illustrate how the factors such as the time delay, the
      immune response to infected cells and viruses, and the proliferation of
      hepatocytes affect the dynamics of the model by numerical simulation.

PMID- 29359155
TI  - The Feasibility of Xpert MTB/RIF Testing to Detect Rifampicin Resistance among
      Childhood Tuberculosis for Prevalence Surveys in Northern China.
AB  - Drug resistance surveillance is crucial for control of drug-resistant
      tuberculosis (TB). However, limited data exists on the burden of drug-resistant
      TB in children. The goal of this work was to generate prevalence data regarding
      rifampicin- (RIF-) resistant childhood TB in northern China and to test the
      feasibility of Xpert for surveying pediatric TB drug resistance prevalence. We
      enrolled 362 clinically diagnosed childhood TB patients and collected sputum,
      gastric lavage aspirate (GLA), bronchoalveolar lavage fluid (BALF), and cerebral
      spinal fluid (CSF) samples. Xpert and solid culture were utilized to detect RIF
      resistance. The detection rate of Xpert-positive TB among new clinically
      diagnosed TB cases was 38.4% (139/362), significantly higher than that of solid
      culture-positive TB (16.3%, 59/362, P < 0.01). Notably, Xpert-positive rates
      differed significantly by sample type, with the highest positive rate for GLA
      (51.2%). The unit testing costs per RIF-resistant TB patient were $828.41 for
      solid culture and $761.86 for Xpert. Our data demonstrate that the prevalence of
      RIF resistance among childhood TB cases in our study (6.9%) is comparable to the
      national RIF resistance prevalence level of new cases (6.7%). In addition, Xpert
      is superior to the solid culture for RIF resistance survey in the childhood TB
      patients.

PMID- 29359158
TI  - Upregulation of Mitf by Phenolic Compounds-Rich Cymbopogon schoenanthus Treatment
      Promotes Melanogenesis in B16 Melanoma Cells and Human Epidermal Melanocytes.
AB  - Melanin provides inherent protection against skin cancer by absorbing broad
      spectrum radiant energy of UV radiation. Cutaneous malignant melanoma incidence
      has recently been observed to increase and the frequency is closely associated
      with the skin color, highlighting the importance of skin pigmentation. Here, we
      showed how melanin biosynthesis is enhanced by treatment with phenolic compounds
      rich Cymbopogon schoenanthus (CYM) in B16 murine melanoma cells and human
      epidermal melanocytes (HEM). CYM increased the melanin content of the cells by
      upregulating the expression of tyrosinase (TYR), tyrosinase-related protein 1
      (TRP1), and dopachrome tautomerase (DCT) at the protein and mRNA levels,
      comparable to the effect of alpha-melanocyte-stimulating hormone (MSH), in both
      B16 cells and HEM. Moreover, global gene expression analysis showed that at least
      44 pigmentation-associated genes were modulated, including the microphthalmia
      associated transcription factor (Mitf) and its transcriptional regulators (Sox10,
      Pax3, and Lef1). Upregulation of copper transport-associated gene Atp7b indicates
      that CYM also promotes tyrosinase activity. CYM upregulated Mitf and possibly
      activates tyrosinase enzyme, providing evidence for its possible use to promote
      melanogenesis and as a therapeutic agent against hypopigmentation disorders.

PMID- 29359159
TI  - The Bioinformatic Analysis of the Dysregulated Genes and MicroRNAs in Entorhinal
      Cortex, Hippocampus, and Blood for Alzheimer's Disease.
AB  - Aim: The incidence of Alzheimer's disease (AD) has been increasing in recent
      years, but there exists no cure and the pathological mechanisms are not fully
      understood. This study aimed to find out the pathogenesis of learning and memory
      impairment, new biomarkers, potential therapeutic targets, and drugs for AD.
      Methods: We downloaded the microarray data of entorhinal cortex (EC) and
      hippocampus (HIP) of AD and controls from Gene Expression Omnibus (GEO) database,
      and then the differentially expressed genes (DEGs) in EC and HIP regions were
      analyzed for functional and pathway enrichment. Furthermore, we utilized the DEGs
      to construct coexpression networks to identify hub genes and discover the small
      molecules which were capable of reversing the gene expression profile of AD.
      Finally, we also analyzed microarray and RNA-seq dataset of blood samples to find
      the biomarkers related to gene expression in brain. Results: We found some
      functional hub genes, such as ErbB2, ErbB4, OCT3, MIF, CDK13, and GPI. According
      to GO and KEGG pathway enrichment, several pathways were significantly
      dysregulated in EC and HIP. CTSD and VCAM1 were dysregulated significantly in
      blood, EC, and HIP, which were potential biomarkers for AD. Target genes of four
      microRNAs had similar GO_terms distribution with DEGs in EC and HIP. In addtion,
      small molecules were screened out for AD treatment. Conclusion: These biological
      pathways and DEGs or hub genes will be useful to elucidate AD pathogenesis and
      identify novel biomarkers or drug targets for developing improved diagnostics and
      therapeutics against AD.

PMID- 29359161
TI  - Factors Influencing Burnout Syndrome in Obstetrics and Gynecology Physicians.
AB  - Aim: To identify the influence of environmental, personality, and alexithymia
      factors on burnout syndrome among obstetrics and gynecology physicians. Material
      and Methods: A total of 116 physicians (35 men and 81 women) completed
      questionnaires and sociodemographic data sheets. The Maslach Burnout Inventory,
      the Big Five Inventory, and the Toronto Alexithymia Scale were used to measure
      burnout, innate personality traits, and alexithymia, respectively. The t-test and
      Pearson correlations were used for other measurements. Results: Of the 116 study
      physicians, 12.9% have suffered or still suffer from depression and 35.3% have
      had or still have problems related to insomnia. Regarding emotional exhaustion
      and depersonalization factors, men obtained lower scores than women (18.73 +/-
      13.48 versus 24.14 +/- 11.71 for emotional exhaustion; 5.97 +/- 5.45 versus 7.70
      +/- 5.29 for depersonalization). Self-reported depression was related to higher
      scores for all 3 domains, to higher total scores for alexithymia and neuroticism,
      and to lower scores for extraversion, conscientiousness, and openness. Residents
      and consultants had markedly different scores. Conclusion: The results of this
      study will help obstetrics and gynecology physicians cope with professional
      burnout and to consider personality traits, alexithymia domains, and
      environmental factors when finding strategies to cope with their professional
      stress.

PMID- 29359160
TI  - Relationship between Physical Activity and Physical Fitness in Preschool
      Children: A Cross-Sectional Study.
AB  - Purpose: To evaluate the relationships between objectively measured physical
      activity and physical fitness among preschool children. Methods: A total of 346
      participants (201 boys and 145 girls) aged 3.5-5.5 years (M = 4.5 yr, SD = 0.47)
      from Shanghai, China, completed physical fitness assessments, including triceps
      skinfold thickness (TSFT), grip strength, tennis throwing, sit and reach test,
      standing long jump, balance beam, 10mSRT, and 20mSRT. Physical activity was
      objectively measured by ActiGraphGT3X+ accelerometer. Multiple linear regression
      models were used to explore the cross-sectional associations between PA and
      physical fitness after adjusting for age, gender, BMI, and valid wearing time.
      Results: Positive associations were observed between stand long jump (p < .01),
      tennis throwing (p < .01), laps in 20mSRT (p < .01), and MVPA. However, TSFT (p <
      .05), time in 10mSRT (p < .01), and balance beam (p < .05) were negatively
      associated with MVPA. Furthermore, positive associations were found between stand
      long jump (p < .01), tennis throwing (p < .01), and MVPA only in boys. Negative
      associations were found between time on balance beam (p < .01) and MVPA only in
      girls. Conclusions: MVPA appears to be an effective and reliable predictor of
      preschoolers' physical fitness. Boys' body composition, muscular strength,
      explosive strength, agility, aerobic fitness, girls' agility, aerobic fitness,
      and balance could improve as MVPA increases.

PMID- 29359163
TI  - Retracted: Tanshinone IIA Induces Apoptosis in Human Oral Cancer KB Cells through
      a Mitochondria-Dependent Pathway.
AB  - [This retracts the article DOI: 10.1155/2014/540516.].

PMID- 29359162
TI  - Natural Bioactive Compounds: Alternative Approach to the Treatment of
      Glioblastoma Multiforme.
AB  - Glioblastoma multiforme (GBM) is the most frequent, primary malignant brain tumor
      prevalent in humans. GBM characteristically exhibits aggressive cell
      proliferation and rapid invasion of normal brain tissue resulting in poor patient
      prognosis. The current standard of care of surgical resection followed by
      radiotherapy and chemotherapy with temozolomide is not very effective. The
      inefficacy of the chemotherapeutic agents may be attributed to the challenges in
      drug delivery to the tumor. Several epidemiological studies have demonstrated the
      chemopreventive role of natural, dietary compounds in the development and
      progression of cancer. Many of these studies have reported the potential of using
      natural compounds in combination with chemotherapy and radiotherapy as a novel
      approach for the effective treatment of cancer. In this paper, we review the role
      of several natural compounds individually and in combination with
      chemotherapeutic agents in the treatment of GBM. We also assess the potential of
      drug delivery approaches such as the Gliadel wafers and role of nanomaterial
      based drug delivery systems for the effective treatment of GBM.

PMID- 29359165
TI  - Corrigendum to "Prediction of Local Ultimate Strain and Toughness of Trabecular
      Bone Tissue by Raman Material Composition Analysis".
AB  - [This corrects the article DOI: 10.1155/2015/457371.].

PMID- 29359164
TI  - Involvement of the PI3K/Akt/NF-kappaB Signaling Pathway in the Attenuation of
      Severe Acute Pancreatitis-Associated Acute Lung Injury by Sedum sarmentosum Bunge
      Extract.
AB  - Sedum sarmentosum Bunge possesses excellent anti-inflammatory properties and was
      used in the treatment of inflammatory diseases. The aim of the present study was
      to investigate the efficiency of Sedum sarmentosum Bunge extract (SSBE) on severe
      acute pancreatitis-associated (SAP-associated) acute lung injury (ALI) in rats
      and to explore the underlying mechanisms. Here, we used a sodium taurocholate
      induced SAP rat model to determine the role of SSBE in ALI. During the course of
      pancreatitis, the expressions of phosphorylated phosphoinositide 3-kinases
      (PI3K)/protein kinase B (Akt) and nuclear factor-kappa B (NF-kappaB) p65 in the
      lungs were upregulated. Meanwhile, a parallel increase in the levels of
      interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor
      alpha (TNF-alpha) in the lungs was observed after the induction of SAP. Treatment
      with SSBE significantly reduced the expression of p-Akt and p-p65 in the lungs
      and attenuated the severity of SAP-associated ALI compared to the SAP group at 12
      h and 24 h. In summary, this study showed that SSBE has beneficial effects on SAP
      associated ALI, probably through the PI3-K/Akt signaling pathways by suppressing
      the NF-kappaB activities.

PMID- 29359166
TI  - Effects of Face-to-Face and Telephone-Based Family-Oriented Education on Self
      Care Behavior and Patient Outcomes in Type 2 Diabetes: A Randomized Controlled
      Trial.
AB  - Background: Education of patients and their families is the cornerstone of
      effective diabetes care. The present study aimed to compare the effects of a face
      to-face and telephone-based family-oriented educational program on self-care
      behavior and patient outcomes in type 2 diabetes patients. Methods: In the
      present randomized controlled trial, 90 type 2 diabetes patients were randomly
      divided into three groups of 30 participants: a face-to-face education group, a
      telephone-based education group, and a control group. The educational program
      lasted for 3 months. Outcomes evaluated included self-care, fasting blood sugar,
      hemoglobin A1c, cholesterol, and triglyceride. Results: The overall self-care
      scores in the intervention groups were significantly higher than that in the
      control group (P = 0.0001). In addition, lipid profiles significantly improved in
      the interventions compared to the control (P < 0.05). Comparing the two
      interventions showed better results for the face-to-face group regarding dietary
      adherence and physical activity, but the latter group had comparable results in
      blood glucose monitoring, foot care, and cholesterol level. Conclusions: This
      study shows the beneficiary effects of a family-oriented education on self-care
      and patient outcomes. It also shows the potential value of low-cost telephone
      technology in delivering effective diabetes care.

PMID- 29359167
TI  - Hmox1 Deficiency Sensitizes Mice to Peroxynitrite Formation and Diabetic
      Glomerular Microvascular Injuries.
AB  - Objective: Indirect evidence suggests a role for heme oxygenase-1 (HO-1) in
      limiting diabetic vasculopathy. The goal of this study was to assess the role of
      HO-1 in the development of microvascular lesions within glomeruli during diabetes
      mellitus using a mouse model with specific alteration of the Hmox1 gene. Approach
      and Results: The effects of Hmox1 haploinsufficiency were studied as a means of
      assessing the intrinsic contribution of HO-1 in the development of renal
      microvascular lesions during diabetes. Renal function and histology were analyzed
      10 weeks after diabetes induction with streptozotocin. Diabetic Hmox1+/- mice
      showed higher levels of albuminuria and blood urea compared to their wild-type
      diabetic littermates. More severe glomerular microvascular lesions were also
      observed in the diabetic Hmox1+/- mice. This was associated with a renal increase
      in the expression of the oxidative stress marker, nitrotyrosine. Conclusions:
      Genetic Hmox1 partial deficiency is sufficient to sensitize mice to the
      development of diabetic glomerular microvascular lesions. HO-1 exerts antioxidant
      effects in the kidney during diabetes mellitus. These have protective effects on
      the development of glomerular endothelial injury.

PMID- 29359168
TI  - SERINC as a Restriction Factor to Inhibit Viral Infectivity and the Interaction
      with HIV.
AB  - The serine incorporator 5 (SERINC5) is a recently discovered restriction factor
      that inhibits viral infectivity by preventing fusion. Retroviruses have developed
      strategies to counteract the action of SERINC5, such as the expression of
      proteins like negative regulatory factor (Nef), S2, and glycosylated Gag
      (glycoGag). These accessory proteins downregulate SERINC5 from the plasma
      membrane for subsequent degradation in the lysosomes. The observed variability in
      the action of SERINC5 suggests the participation of other elements like the
      envelope glycoprotein (Env) that modulates susceptibility of the virus towards
      SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet
      been determined, although it has been proposed that it increases the sensitivity
      of the Env by exposing regions which are recognized by neutralizing antibodies.
      More studies are needed to understand the role of SERINC5 and to assess its
      utility as a therapeutic strategy.

PMID- 29359171
TI  - Prevalence and Factors Associated with Low Birth Weight among Teenage Mothers in
      New Mulago Hospital: A Cross Sectional Study.
AB  - The World Health Organization defines low birth weight (LBW) as a new born having
      a weight of less than 2,500 g at birth. Low birth weight is one of the major
      determinants of perinatal survival, infant morbidity and mortality as well as the
      risk of developmental disabilities and illnesses in future lives. WHO estimates
      that about 30 million low birth weight babies are born annually (23.4% of all
      births) and they often face short and long term health consequences. Whereas the
      global prevalence of LBW has slightly declined, the rate in many developing
      countries is still quite high. In Uganda, low birth weight among teenage mothers
      is a problem. Our study aimed to estimate the prevalence of and identify the
      factors associated with low birth weight among teenage mothers in New Mulago
      hospital. We conducted an analytical cross sectional study among teenage mothers
      who delivered from new Mulago Hospital Complex labour suite from August 2013 to
      August 2014. Trained interviewers, administered pre-tested questionnaires to
      consecutive mothers to obtain information on their socio-demographic
      characteristics, obstetric history and child factors. Odds ratios and P-values
      were calculated to determine the relationship between independent and dependent
      variables. We also used descriptive statistics for the quantitative data. A total
      of 357 teenage mothers were enrolled on the study. Their mean age was 18 years
      (Range 13-19), majority, 98.4% aged 15-19 years. The prevalence of LBW was 25.5%.
      Pre-term delivery (OR = 3.3032 P = 0.0001) and multiple pregnancies (OR = 0.165 P
      = 0.039) were associated with LBW. Malaria, young maternal age and ANC attendance
      were not associated with LBW. Child factors such as birth order, congenital
      anomalies and sex of the baby were also not associated with LBW. The prevalence
      of LBW is high among teenage mothers, pre-term delivery and multiple pregnancies
      were associated factors with LBW. Health professional's need to address teenage
      maternal health. Health workers should encourage teenage mothers to attend
      focused antenatal care as recommended by the Uganda ministry of Health. A
      specialized maternal facility centre that is friendly for adolescent/teenage
      mothers is advisable so as to improve on completion rates and capture high risk
      teenage mothers early.

PMID- 29359169
TI  - Pathological Roles of Neutrophil-Mediated Inflammation in Asthma and Its
      Potential for Therapy as a Target.
AB  - Asthma is a chronic inflammatory disease that undermines the airways. It is
      caused by dysfunction of various types of cells, as well as cellular components,
      and is characterized by recruitment of inflammatory cells, bronchial
      hyperreactivity, mucus production, and airway remodelling and narrowing. It has
      commonly been considered that airway inflammation is caused by the Th2 immune
      response, or eosinophilia, which is a hallmark of bronchial asthma pathogenesis.
      Some patients display a neutrophil-dominant presentation and are characterized
      with low (or even absent) Th2 cytokines. In recent years, increasing evidence has
      also suggested that neutrophils play a key role in the development of certain
      subtypes of asthma. This review discusses neutrophils in asthma and potentially
      related targeted therapies.

PMID- 29359170
TI  - Early-Life Intestine Microbiota and Lung Health in Children.
AB  - The gastrointestinal microbiota plays a critical role in nutritional, metabolic,
      and immune functions in infants and young children and has implications for
      future lung health status. Understanding the role of intestinal dysbiosis in
      chronic lung disease progression will provide opportunities to design early
      interventions to improve the course of the disease. Gut microbiota is established
      within the first 1 to 3 years of life and remains relatively stable throughout
      the life span. In this review, we report the recent development in research in
      gut-lung axis, with focus on the effects of targeting microbiota of infants and
      children at risk of or with progressive lung diseases. The basic concept is to
      exploit this approach in critical window to achieve the best results in the
      control of future health.

PMID- 29359172
TI  - Nonclinical Safety Evaluation of scAAV8-RLBP1 for Treatment of RLBP1 Retinitis
      Pigmentosa.
AB  - Retinitis pigmentosa is a form of retinal degeneration usually caused by genetic
      mutations affecting key functional proteins. We have previously demonstrated
      efficacy in a mouse model of RLBP1 deficiency with a self-complementary AAV8
      vector carrying the gene for human RLBP1 under control of a short RLBP1 promoter
      (CPK850).1 In this article, we describe the nonclinical safety profile of this
      construct as well as updated efficacy data in the intended clinical formulation.
      In Rlbp1-/- mice dosed at a range of CPK850 levels, a minimum efficacious dose of
      3 * 107 vg in a volume of 1 MUL was observed. For safety assessment in these and
      Rlbp1+/+ mice, optical coherence tomography (OCT) and histopathological analysis
      indicated retinal thinning that appeared to be dose-dependent for both Rlbp1
      genotypes, with no qualitative difference noted between Rlbp1+/+ and Rlbp1-/-
      mice. In a non-human primate study, RLBP1 mRNA expression was detected and dose
      dependent intraocular inflammation and retinal thinning were observed.
      Inflammation resolved slowly over time and did not appear to be exacerbated in
      the presence of anti-AAV8 antibodies. Biodistribution was evaluated in rats and
      satellite animals in the non-human primate study. The vector was largely detected
      in ocular tissues and low levels in the optic nerve, superior colliculus, and
      lateral geniculate nucleus, with limited distribution outside of these tissues.
      These data suggest that an initial subretinal dose of ~3 * 107 vg/MUL CPK850 can
      safely be used in clinical trials.

PMID- 29359173
TI  - Immune myopathies with perimysial pathology: Clinical and laboratory features.
AB  - Objective: Immune myopathies with perimysial pathology (IMPP) have a combination
      of damage to perimysial connective tissue and muscle fiber necrosis, more
      prominent near the perimysium. We studied the clinical and laboratory correlates
      of patients with pathologically defined IMPP. Methods: This is a retrospective
      chart and pathology review of 57 consecutive patients with IMPP myopathology and,
      for comparison, 20 patients with dermatomyositis with vascular pathology (DM-VP).
      Results: Compared with DM-VP, IMPP patients more commonly had interstitial lung
      disease (ILD) (p < 0.01), Raynaud phenomenon (p < 0.05), mechanic's hands (p <
      0.05), arthralgias (p < 0.001), and a sustained response to immunomodulatory
      therapy (p < 0.05), and less frequently had a concurrent malignancy (p < 0.01).
      IMPP patients had higher serum creatine kinase values (p < 0.05), more frequent
      serum Jo-1 (p < 0.03) or SSA/SSA52 autoantibodies (p < 0.05), and less frequent
      antinuclear antibodies (p < 0.01). IMPP patients with serum Jo-1/antisynthetase
      antibodies were more likely to have ILD (p < 0.05) and inflammatory arthritis (p
      < 0.05) than IMPP patients without these antibodies. Conclusions: IMPP
      myopathology is associated with an increased risk of ILD, Raynaud phenomenon,
      mechanic's hands, and inflammatory arthritis when compared with another immune
      myopathy (DM-VP). IMPP patients require regular screening for ILD, particularly
      those with antisynthetase antibodies. The absence of myositis-specific
      autoantibodies in a large percentage of IMPP patients emphasizes the important
      role for myopathology in identifying patients at higher risk of severe comorbid
      conditions such as ILD.

PMID- 29359174
TI  - Quantitative spinal cord MRI in radiologically isolated syndrome.
AB  - Objectives: To assess whether quantitative spinal cord MRI (SC-MRI) measures,
      including atrophy, and diffusion tensor imaging (DTI) and magnetization transfer
      imaging metrics were different in radiologically isolated syndrome (RIS) vs
      healthy controls (HCs). Methods: Twenty-four participants with RIS and 14 HCs
      underwent cervical SC-MRI on a 3T magnet. Manually segmented regions of interest
      circumscribing the spinal cord cross-sectional area (SC-CSA) between C3 and C4
      were used to extract SC-CSA, fractional anisotropy, mean, perpendicular, and
      parallel diffusivity (MD, lambda?, and lambda||) and magnetization transfer ratio
      (MTR). Spinal cord (SC) lesions, SC gray matter (GM), and SC white matter (WM)
      areas were also manually segmented. Multivariable linear regression was performed
      to evaluate differences in SC-MRI measures in RIS vs HCs, while controlling for
      age and sex. Results: In this cross-sectional study of participants with RIS, 71%
      had lesions in the cervical SC. Of quantitative SC-MRI metrics, spinal cord MTR
      showed a trend toward being lower in RIS vs HCs (p = 0.06), and there was already
      evidence of brain atrophy (p = 0.05). There were no significant differences in SC
      DTI metrics, GM, WM, or CSA between RIS and HCs. Conclusion: The SC demonstrates
      minimal microstructural changes suggestive of demyelination and inflammation in
      RIS. These findings are in contrast to established MS and raise the possibility
      that the SC may play an important role in triggering clinical symptomatology in
      MS. Prospective follow-up of this cohort will provide additional insights into
      the role the SC plays in the complex sequence of events related to MS disease
      initiation and progression.

PMID- 29359175
TI  - Defining standard enzymatic dissociation methods for individual brains and spinal
      cords in EAE.
AB  - Objective: To determine the capacity, effectiveness, efficiency, and reliability
      of select tissue dissociation methods to isolate mononuclear cells from the CNS
      of mice with experimental autoimmune encephalomyelitis (EAE). Methods: As part of
      an assay qualification, we tested the isolation method Percoll PLUS vs a
      commercially available enzymatic Neural Tissue Dissociation Kit (Kit), and the
      enzymes accutase and papain in C57BL/6 mice with active EAE. In a stepwise
      approach, we applied the following 4 criteria to each dissociation method: (1)
      mononuclear cell viability post-processing was required to be >=80% per brain or
      spinal cord sample, (2) absolute live mononuclear cell numbers was required to be
      >=5 * 105 per brain or spinal cord sample of mice with clinical EAE, (3) test
      retest reliability had to be verified, and (4) the absolute mononuclear cell
      numbers in brain and spinal cord had to correlate with the EAE disease course.
      Results: Enzymatic dissociations allowed for greatly increased cell yield and
      specifically allowed for downstream assays from individual brains and spinal
      cords in C57BL/6 mice with EAE. All enzymatic dissociations provided a more
      efficient and effective method for isolating mononuclear cells from brains and
      spinal cord. Only the Kit assay provided a significant correlation between
      absolute mononuclear cell numbers in the spinal cord and EAE disease severity.
      Conclusions: Enzymatic dissociation of CNS tissue of C57BL/6 mice with active EAE
      with the Kit should be the standard method. The identification of optimized CNS
      dissociation methods in EAE has the potential to identify cellular events that
      are pertinent to MS pathogenesis.

PMID- 29359176
TI  - Spatiotemporal evolution of venous narrowing in acute MS lesions.
AB  - Objective: To investigate the spatiotemporal evolution of venous narrowing in
      newly developing MS lesions in a longitudinal MRI study including susceptibility
      weighted images (SWIs). Methods: We retrospectively investigated serial MR
      examinations of 18 patients with MS acquired on a 3T MRI system including SWI for
      acute contrast-enhancing lesions with at least 1 MRI examination before contrast
      enhancement. The mean diameter of veins at the time point of contrast enhancement
      was compared with the mean diameter of veins before and after contrast
      enhancement. Results: A total of 40 acute contrast-enhancing lesions with a
      corresponding intralesional central vein were included in the study. The mean
      diameter of intralesional veins at the time of contrast enhancement (0.80 +/-
      0.12 mm) was smaller than that at before (1.16 +/- 0.19 mm) and after contrast
      enhancement (1.07 +/- 0.15 mm; p < 0.001 for all comparisons). Conclusions: Our
      findings contribute to the increasing database of plaque development and
      evolution. The smaller diameter of intralesional veins on SWI at the time of
      blood-brain barrier breakdown may reflect morphologic changes because of
      perivascular inflammation and/or decreased levels of deoxygenated hemoglobin.

PMID- 29359177
TI  - Resource Partitioning between Two Piranhas (Serrasalmus gibbus and Serrasalmus
      rhombeus) in an Amazonian Reservoir.
AB  - The exploitation of resources by closely related species with similar niches may
      be mediated by differences in activity patterns, which may vary in nycthemeral
      scale and seasonal scale. Piranhas Serrasalmus gibbus and Serrasalmus rhombeus
      are Neotropical predators that occur sympatrically in many environments of the
      Amazon basin. To evaluate the strategies adopted by these two species in a
      restricted environment (a reservoir), nycthemeral and seasonal samples were made,
      identifying the composition of the diet and their activity patterns. A total of
      402 specimens were collected: 341 S. gibbus and 61 S. rhombeus. Both species fed
      themselves primarily on fish, with some seasonal variation being found in S.
      gibbus during the flood season, when plant material was consumed. There was
      considerable temporal overlap in the foraging behavior of the two species,
      although S. rhombeus presented a bimodal pattern of abundance over the 24-hour
      cycle. S. rhombeus was more active during the nighttime, between dusk and early
      morning, whereas S. gibbus was active throughout the nycthemeral cycle. These
      findings indicate low levels of competition between the two species, which
      allowed for a considerable overlap in nighttime foraging, following distinct
      nycthemeral patterns of foraging activity and allowing their coexistence.

PMID- 29359178
TI  - The Impact of Saffron on Symptoms of Withdrawal Syndrome in Patients Undergoing
      Maintenance Treatment for Opioid Addiction in Sabzevar Parish in 2017.
AB  - Background and Objective: Drug dependence is one of the serious problems around
      the world. Saffron is one of those beneficial medicinal plants which is embedded
      with a similar mechanism to methadone (e.g., inhibition of serotonin reuptake).
      Thus, it can be helpful in reducing the withdrawal symptoms. The aim of this
      study was to reduce the daily dose of methadone usage and reduce its side effects
      using saffron in the form of medicinal supplements. Methodology: This study was
      categorized as a clinical trial. Accordingly, 44 clients of addiction treatment
      centers in Sabzevar parish were randomly selected to participate in this study in
      2016-2017. While the experimental group was treated with methadone syrup and self
      made saffron capsules, the control group received methadone syrup and placebo
      capsules. Results: The results showed that the use of saffron and methadone
      alleviated the symptoms of withdrawal syndrome (p<0.001). Conclusion: Having
      reviewed the research participants, it was indicated that the introduction of
      saffron alleviated the symptoms of withdrawal syndrome in patients undergoing
      maintenance treatment for opioid addiction. Thus, it seems rational to make use
      of saffron in combination with methadone in order to alleviate the symptoms of
      withdrawal syndrome.

PMID- 29359179
TI  - Erratum to "Nutritional Considerations for Performance in Young Athletes".
AB  - [This corrects the article DOI: 10.1155/2015/734649.].

PMID- 29359180
TI  - Nuclear, Cytosolic, and Surface-Localized Poly(A)-Binding Proteins of Plasmodium
      yoelii.
AB  - Malaria is a devastating illness that causes approximately 500,000 deaths
      annually. The malaria-causing parasite (Plasmodium genus) uses the process of
      translational repression to regulate its growth, development, and transmission.
      As poly(A)-binding proteins (PABP) have been identified as critical components of
      RNA metabolism and translational repression in model eukaryotes and in
      Plasmodium, we have identified and investigated two PABPs in Plasmodium yoelii,
      PyPABP1 and PyPABP2. In contrast to most single-celled eukaryotes, Plasmodium
      closely resembles metazoans and encodes both a nuclear PABP and a cytosolic PABP;
      here, we provide multiple lines of evidence in support of this observation. The
      conserved domain architectures of PyPABP1 and PyPABP2 resemble those of yeast and
      metazoans, while multiple independent binding assays demonstrated their ability
      to bind very strongly and specifically to poly(A) sequences. Interestingly, we
      also observed that purified PyPABP1 forms homopolymeric chains despite exhaustive
      RNase treatment in vitro. Finally, we show by indirect immunofluorescence assays
      (IFAs) that PyPABP1 and PyPABP2 are cytoplasm- and nucleus-associated PABPs
      during the blood stages of the life cycle. Surprisingly, however, PyPABP1 was
      instead observed to also be localized on the surface of transmitted salivary
      gland sporozoites and to be deposited in trails when parasites glide on a
      substrate. This is the third RNA-binding protein verified to be found on the
      sporozoite surface, and the data may point to an unappreciated RNA-centered
      interface between the host and parasite. IMPORTANCE Malaria remains one of the
      great global health problems. The parasite that causes malaria (Plasmodium genus)
      relies upon exquisite control of its transmission between vertebrate hosts and
      mosquitoes. One crucial way that it does so is by proactively producing mRNAs
      needed to establish the new infection but by silencing and storing them until
      they are needed. One key protein in this process of translational repression in
      model eukaryotes is poly(A)-binding protein (PABP). Here we have shown that
      Plasmodium yoelii utilizes both a nuclear PABP and a cytosolic PABP, both of
      which bind specifically to polyadenylated RNA sequences. Moreover, we find that
      the cytosolic PABP forms chains in vitro, consistent with its appreciated role in
      coating the poly(A) tails of mRNA. Finally, we have also verified that,
      surprisingly, the cytosolic PABP is found on the surface of Plasmodium
      sporozoites. Taking the data together, we propose that Plasmodium utilizes a more
      metazoan-like strategy for RNA metabolism using specialized PABPs.

PMID- 29359181
TI  - Development and Validation of a Serologic Test Panel for Detection of Powassan
      Virus Infection in U.S. Patients Residing in Regions Where Lyme Disease Is
      Endemic.
AB  - Powassan virus (POWV) is an emerging tick-borne arbovirus presenting a public
      health threat in North America. POWV lineage II, also known as deer tick virus,
      is the strain of the virus most frequently found in Ixodes scapularis ticks and
      is implicated in most cases of POWV encephalitis in the United States. Currently,
      no commercial tests are available to detect POWV exposure in tick-borne disease
      (TBD) patients. We describe here the development and analytical validation of a
      serologic test panel to detect POWV infections. The panel uses an indirect enzyme
      immunoassay (EIA) to screen. EIA-positive samples reflex to a laboratory
      developed, POWV-specific immunofluorescence assay (IFA). The analytical
      sensitivity of the test panel was 89%, and the limit of detection was a plaque
      reduction neutralization test (PRNT) titer of 1:20. The analytical specificity
      was 100% for the IgM assay and 65% for the IgG assay when heterologous-flavivirus
      positive samples were tested. On samples collected from regions where Lyme
      disease is endemic, seroprevalence for POWV in TBD samples was 9.4% (10 of 106)
      versus 2% when tested with non-TBD samples (2 of 100, P = 0.034). No evidence of
      POWV infection was seen in samples collected from a region where Lyme disease was
      not endemic (0 of 22). This test panel provides a sensitive and specific platform
      for detecting a serologic response to POWV early in the course of infection when
      neutralizing antibodies may not be detectable. Combined with clinical history,
      the panel is an effective tool for identifying acute POWV infection. IMPORTANCE
      Approximately 100 cases of POWV disease were reported in the United States over
      the past 10 years. Most cases have occurred in the Northeast (52) and Great Lakes
      (45) regions (https://www.cdc.gov/powassan/statistics.html). The prevalence of
      POWV in ticks and mammals is increasing, and POWV poses an increasing threat in a
      greater geographical range. In areas of the Northeast and Midwest where Lyme
      disease is endemic, POWV testing is recommended for patients with a recent tick
      bite, patients with Lyme disease who have been treated with antibiotics, or
      patients with a tick exposure who have tested negative for Lyme disease or other
      tick-borne illnesses and have persistent symptoms consistent with posttreatment
      Lyme disease. Testing could also benefit patients with tick exposure and
      unexplained neurologic symptoms and chronic fatigue syndrome (CFS) patients with
      known tick exposure. Until now, diagnostic testing for Powassan virus has not
      been commercially available and has been limited to patients presenting with
      severe, neurologic complications. The lack of routine testing for Powassan virus
      in patients with suspected tick-borne disease means that little information is
      available regarding the overall prevalence of the virus and the full spectrum of
      clinical symptoms associated with infection. As Ixodes scapularis is the tick
      vector for Powassan virus and multiple other tick-borne pathogens, including the
      Lyme disease bacterium, Borrelia burgdorferi, the clinical presentations and long
      term outcomes of Powassan virus infection and concurrent infection with other
      tick-borne disease pathogens remain unknown.

PMID- 29359182
TI  - Mitochondrial Voltage-Dependent Anion Channel Protein Por1 Positively Regulates
      the Nuclear Localization of Saccharomyces cerevisiae AMP-Activated Protein
      Kinase.
AB  - Snf1 protein kinase of the yeast Saccharomyces cerevisiae is a member of the
      highly conserved eukaryotic AMP-activated protein kinase (AMPK) family, which is
      involved in regulating responses to energy limitation. Under conditions of
      carbon/energy stress, such as during glucose depletion, Snf1 is catalytically
      activated and enriched in the nucleus to regulate transcription. Snf1 catalytic
      activation requires phosphorylation of its conserved activation loop threonine
      (Thr210) by upstream kinases. Catalytic activation is also a prerequisite for
      Snf1's subsequent nuclear enrichment, a process that is mediated by Gal83, one of
      three alternate beta-subunits of the Snf1 kinase complex. We previously reported
      that the mitochondrial voltage-dependent anion channel (VDAC) proteins Por1 and
      Por2 play redundant roles in promoting Snf1 catalytic activation by Thr210
      phosphorylation. Here, we show that the por1Delta mutation alone, which by itself
      does not affect Snf1 Thr210 phosphorylation, causes defects in Snf1 and Gal83
      nuclear enrichment and Snf1's ability to stimulate transcription. We present
      evidence that Por1 promotes Snf1 nuclear enrichment by promoting the nuclear
      enrichment of Gal83. Overexpression of Por2, which is not believed to have
      channel activity, can suppress the localization and transcription activation
      defects of the por1Delta mutant, suggesting that the regulatory role played by
      Por1 is separable from its channel function. Thus, our findings expand the
      positive roles of the yeast VDACs in carbon/energy stress signaling upstream of
      Snf1. Since AMPK/Snf1 and VDAC proteins are conserved in evolution, our findings
      in yeast may have implications for AMPK regulation in other eukaryotes, including
      humans. IMPORTANCE AMP-activated protein kinases (AMPKs) sense energy limitation
      and regulate transcription and metabolism in eukaryotes from yeast to humans. In
      mammals, AMPK responds to increased AMP-to-ATP or ADP-to-ATP ratios and is
      implicated in diabetes, heart disease, and cancer. Mitochondria produce ATP and
      are generally thought to downregulate AMPK. Indeed, some antidiabetic drugs
      activate AMPK by affecting mitochondrial respiration. ATP release from
      mitochondria is mediated by evolutionarily conserved proteins known as voltage
      dependent anion channels (VDACs). One would therefore expect VDACs to serve as
      negative regulators of AMPK. However, our experiments in yeast reveal the
      existence of an opposite relationship. We previously showed that Saccharomyces
      cerevisiae VDACs Por1 and Por2 positively regulate AMPK/Snf1 catalytic
      activation. Here, we show that Por1 also plays an important role in promoting
      AMPK/Snf1 nuclear localization. Our counterintuitive findings could inform
      research in areas ranging from diabetes to cancer to fungal pathogenesis.

PMID- 29359183
TI  - Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent
      Oral SHIV Acquisition in Infant Macaques.
AB  - Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV
      1) contributes to an estimated 150,000 new infections annually. Maternal
      vaccination has proven safe and effective at mitigating the impact of other
      neonatal pathogens and is one avenue toward generating the potentially protective
      immune responses necessary to inhibit HIV-1 infection of infants through
      breastfeeding. In the present study, we tested the efficacy of a maternal vaccine
      regimen consisting of a modified vaccinia virus Ankara (MVA) 1086.C gp120 prime
      combined intramuscular-intranasal gp120 boost administered during pregnancy and
      postpartum to confer passive protection on infant rhesus macaques against weekly
      oral exposure to subtype C simian-human immunodeficiency virus 1157ipd3N4
      (SHIV1157ipd3N4) starting 6 weeks after birth. Despite eliciting a robust
      systemic envelope (Env)-specific IgG response, as well as durable milk IgA
      responses, the maternal vaccine did not have a discernible impact on infant oral
      SHIV acquisition. This study revealed considerable variation in vaccine-elicited
      IgG placental transfer and a swift decline of both Env-specific antibodies (Abs)
      and functional Ab responses in the infants prior to the first challenge,
      illustrating the importance of pregnancy immunization timing to elicit optimal
      systemic Ab levels at birth. Interestingly, the strongest correlation to the
      number of challenges required to infect the infants was the percentage of
      activated CD4+ T cells in the infant peripheral blood at the time of the first
      challenge. These findings suggest that, in addition to maternal immunization,
      interventions that limit the activation of target cells that contribute to
      susceptibility to oral HIV-1 acquisition independently of vaccination may be
      required to reduce infant HIV-1 acquisition via breastfeeding. IMPORTANCE Without
      novel strategies to prevent mother-to-child HIV-1 transmission, more than 5% of
      HIV-1-exposed infants will continue to acquire HIV-1, most through breastfeeding.
      This study of rhesus macaque dam-and-infant pairs is the first preclinical study
      to investigate the protective role of transplacentally transferred HIV-1 vaccine
      elicited antibodies and HIV-1 vaccine-elicited breast milk antibody responses in
      infant oral virus acquisition. It revealed highly variable placental transfer of
      potentially protective antibodies and emphasized the importance of pregnancy
      immunization timing to reach peak antibody levels prior to delivery. While there
      was no discernible impact of maternal immunization on late infant oral virus
      acquisition, we observed a strong correlation between the percentage of activated
      CD4+ T cells in infant peripheral blood and a reduced number of challenges to
      infection. This finding highlights an important consideration for future studies
      evaluating alternative strategies to further reduce the vertical HIV-1
      transmission risk.

PMID- 29359185
TI  - Antibiotic Treatments for Clostridium difficile Infection Are Associated with
      Distinct Bacterial and Fungal Community Structures.
AB  - Clostridium difficile infection (CDI) is the most common nosocomial infection in
      the United States, being associated with high recurrence and persistence rates.
      Though the relationship between intestinal dysbiosis and CDI is well known, it is
      unclear whether different forms of dysbiosis may potentially affect the course of
      CDI. How this is further influenced by C. difficile-directed antibiotics is
      virtually uninvestigated. In this study, diarrheal stool samples were collected
      from 20 hospitalized patients, half of whom were confirmed to have CDI. Analyzing
      tissue ex vivo and in duplicate, CDI and non-CDI fecal samples (n = 176) were
      either not antibiotic treated or treated with metronidazole, vancomycin, or
      fidaxomicin, the three most common CDI therapies. The microbial community
      composition, interactions, and predicted metabolic functions were assessed by 16S
      rRNA gene and internal transcribed spacer sequencing, bipartite network analysis,
      and phylogenetic investigation of communities by reconstruction of unobserved
      states. Our results demonstrate that while all C. difficile-directed antibiotics
      were associated with similar reductions in alpha diversity, beta diversity
      significantly differed on the basis of the particular antibiotic, with
      differentiating relative abundances of bacterial and fungal assemblages. With the
      exception of fidaxomicin, each antibiotic was associated with the emergence of
      potentially pathogenic fungal operational taxonomic units, with predicted
      bacterial functions enriched for xenobiotic metabolism that could perpetuate the
      dysbiosis driving CDI. Toxin-independent mechanisms of colitis related to the
      relative abundance of pathogenic bacteria and fungi were also noted. This study
      suggests that a transkingdom interaction between fungi and bacteria may be
      important in CDI pathophysiology, including being a factor in the historically
      high persistence and recurrence rates associated with this disease. IMPORTANCE
      Using human fecal samples and including sequencing for both bacterial and fungal
      taxa, this study compared the conventional antibiotics used to treat C. difficile
      infection (CDI) from the perspective of the microbiome, which is particularly
      relevant, given the relationship between dysbiotic states and the development of
      CDI. Sequencing and imputed functional analyses suggest that C. difficile
      directed antibiotics are associated with distinct forms of dysbiosis that may be
      influential in the course of CDI. Further, a role for fungal organisms in the
      perpetuation of the causal dysbiosis of CDI is discussed, suggesting a previously
      unappreciated, clinically relevant transkingdom interaction that warrants further
      study.

PMID- 29359184
TI  - Prey Range and Genome Evolution of Halobacteriovorax marinus Predatory Bacteria
      from an Estuary.
AB  - Halobacteriovorax strains are saltwater-adapted predatory bacteria that attack
      Gram-negative bacteria and may play an important role in shaping microbial
      communities. To understand how Halobacteriovorax strains impact ecosystems and
      develop them as biocontrol agents, it is important to characterize variation in
      predation phenotypes and investigate Halobacteriovorax genome evolution. We
      isolated Halobacteriovorax marinus BE01 from an estuary in Rhode Island using
      Vibrio from the same site as prey. Small, fast-moving, attack-phase BE01 cells
      attach to and invade prey cells, consistent with the intraperiplasmic predation
      strategy of the H. marinus type strain, SJ. BE01 is a prey generalist, forming
      plaques on Vibrio strains from the estuary, Pseudomonas from soil, and
      Escherichia coli. Genome analysis revealed extremely high conservation of gene
      order and amino acid sequences between BE01 and SJ, suggesting strong selective
      pressure to maintain the genome in this H. marinus lineage. Despite this, we
      identified two regions of gene content difference that likely resulted from
      horizontal gene transfer. Analysis of modal codon usage frequencies supports the
      hypothesis that these regions were acquired from bacteria with different codon
      usage biases than H. marinus. In one of these regions, BE01 and SJ carry
      different genes associated with mobile genetic elements. Acquired functions in
      BE01 include the dnd operon, which encodes a pathway for DNA modification, and a
      suite of genes involved in membrane synthesis and regulation of gene expression
      that was likely acquired from another Halobacteriovorax lineage. This analysis
      provides further evidence that horizontal gene transfer plays an important role
      in genome evolution in predatory bacteria. IMPORTANCE Predatory bacteria attack
      and digest other bacteria and therefore may play a role in shaping microbial
      communities. To investigate phenotypic and genotypic variation in saltwater
      adapted predatory bacteria, we isolated Halobacteriovorax marinus BE01 from an
      estuary in Rhode Island, assayed whether it could attack different prey bacteria,
      and sequenced and analyzed its genome. We found that BE01 is a prey generalist,
      attacking bacteria from different phylogenetic groups and environments. Gene
      order and amino acid sequences are highly conserved between BE01 and the H.
      marinus type strain, SJ. By comparative genomics, we detected two regions of gene
      content difference that likely occurred via horizontal gene transfer events.
      Acquired genes encode functions such as modification of DNA, membrane synthesis
      and regulation of gene expression. Understanding genome evolution and variation
      in predation phenotypes among predatory bacteria will inform their development as
      biocontrol agents and clarify how they impact microbial communities.

PMID- 29359186
TI  - Recombinant Zika Virus Subunits Are Immunogenic and Efficacious in Mice.
AB  - Following the 2015 Zika virus (ZIKV) outbreaks in the South Pacific, Caribbean,
      and Americas, ZIKV has emerged as a serious threat due to its association with
      infantile microcephaly and other neurologic disorders. Despite an international
      effort to develop a safe and effective vaccine to combat congenital Zika syndrome
      and ZIKV infection, only DNA and mRNA vaccines encoding the precursor membrane
      (prM) and envelope (E) proteins, an inactivated-ZIKV vaccine, and a measles virus
      based ZIKV vaccine are currently in phase I or II (prM/E DNA) clinical trials. A
      ZIKV vaccine based on a nonreplicating, recombinant subunit platform offers a
      higher safety profile than other ZIKV vaccine candidates but is still highly
      immunogenic, inducing high virus-neutralizing antibody titers. Here, we describe
      the production and purification of Drosophila melanogaster S2 insect cell
      derived, soluble ZIKV E protein and evaluate its immunogenicity and efficacy in
      three different mouse strains. As expected, significant virus-specific antibody
      titers were observed when using formulations containing clinically relevant
      adjuvants. Immunized mice challenged with live virus demonstrate inhibition of
      virus replication. Importantly, plaque reduction neutralization tests (PRNTs)
      indicate the high-titer production of neutralizing antibodies, a correlate of
      protection in the defense against ZIKV infection. ZIKV challenge of
      immunocompetent mice led to full protection against viremia with two doses of
      adjuvanted vaccine candidates. These data demonstrate a proof of concept and
      establish recombinant subunit immunogens as an effective vaccine candidate
      against ZIKV infection. IMPORTANCE The recent outbreaks of Zika virus (ZIKV)
      infection in French Polynesia, the Caribbean, and the Americas have highlighted
      the severe neuropathological sequelae that such an infection may cause. The
      development of a safe, effective ZIKV vaccine is critical for several reasons:
      (i) the difficulty in diagnosing an active infection due to common nonspecific
      symptoms, (ii) the lack of a specific antiviral therapy, and (iii) the
      potentially devastating pathological effects of in utero infection. Moreover, a
      vaccine with an excellent safety profile, such as a nonreplicating, noninfectious
      vaccine, would be ideal for high-risk people (e.g., pregnant women,
      immunocompromised patients, and elderly individuals). This report describes the
      development of a recombinant subunit protein vaccine candidate derived from
      stably transformed insect cells expressing the ZIKV envelope protein in vitro,
      the primary antigen to which effective virus-neutralizing antibodies are
      engendered by immunized animals for several other flaviviruses; the vaccine
      candidate elicits effective virus-neutralizing antibodies against ZIKV and
      provides protection against ZIKV infection in mice.

PMID- 29359187
TI  - The Small RNA ncS35 Regulates Growth in Burkholderia cenocepacia J2315.
AB  - Burkholderia cenocepacia J2315 is a member of the B. cepacia complex. It has a
      large genome with three replicons and one plasmid; 7,261 genes code for annotated
      proteins, while 113 code for functional RNAs. Small regulatory RNAs of B.
      cenocepacia have not yet been functionally characterized. We investigated a small
      regulatory RNA, designated ncS35, that was discovered by differential RNA
      sequencing. Its expression under various conditions was quantified, and a
      deletion mutant, DeltancS35, was constructed. Compared to planktonic growth in a
      rich medium, the expression of ncS35 was elevated when B. cenocepacia J2315 was
      grown in biofilms and in minimal medium. Cells of the deletion mutant showed
      increased aggregation, higher metabolic activity, a higher growth rate, and an
      increased susceptibility to tobramycin. A transcriptomic analysis revealed
      upregulation of the phenylacetic acid and tryptophan degradation pathways in
      DeltancS35. Computational target prediction indicated that ncS35 likely interacts
      with the first gene of the tryptophan degradation pathway. Overall, we
      demonstrated that small RNA ncS35 is a noncoding RNA with an attenuating effect
      on the metabolic rate and growth. It is possible that slower growth protects B.
      cenocepacia J2315 against stressors acting on fast-dividing cells and enhances
      survival under unfavorable conditions. IMPORTANCE Small RNAs play an important
      role in the survival of bacteria in diverse environments. We explored the
      physiological role of ncS35, a small RNA expressed in B. cenocepacia J2315, an
      opportunistic pathogen in cystic fibrosis patients. In cystic fibrosis patients,
      infections can lead to "cepacia syndrome," a rapidly progressing and often fatal
      pneumonia. Infections with Burkholderia spp. are difficult to threat with
      antibiotics because of their high intrinsic resistance and ability to form
      biofilms. We show that ncS35 attenuates the growth and reduces the metabolic rate
      of B. cenocepacia and influences biofilm structure. This demonstrates that as-yet
      uncharacterized small RNAs with regulatory function can influence physiological
      traits of B. cenocepacia that are relevant for infection.

PMID- 29359188
TI  - Identification of Head and Neck Cancer Subtypes Based on Human Papillomavirus
      Presence and E2F-Regulated Gene Expression.
AB  - Human papillomavirus (HPV) is present in a subset of head and neck squamous cell
      carcinomas (HNSCCs). The cell cycle regulatory Rb-E2F pathway is a major target
      of HPV and is perturbed by these viruses in cell culture and animal models, as
      well as in human tumors. In this study, we examined differences in the Rb-E2F
      pathway displayed by HPV-positive (HPV+) and HPV-negative (HPV-) HNSCC tumors. We
      created a computational approach that effectively categorizes gene expression as
      unchanged, downregulated, or upregulated by comparing the gene's mRNA levels in
      the tumor to the corresponding mRNA levels across normal tissue samples. Our
      findings suggest that there are three major HNSCC subtypes, defined by
      differences in the presence of HPV and in E2F-regulated gene expression. Most
      HPV+ HNSCC tumors show upregulation of E2F-regulated genes, which is consistent
      with inactivation of Rb by the virus-encoded E7 protein. In contrast, many HPV-
      HNSCCs show little or no change in the Rb-E2F pathway. However, we also
      identified a set of tumors that show alterations in the Rb-E2F pathway in the
      absence of HPV. Thus, one class of HPV- HNSCCs arise without significant
      alterations of the Rb-E2F pathway, while a second class of tumors appear to
      deregulate this pathway independently of the presence of HPV. IMPORTANCE Cancer
      is a complex disease that can be caused by a multitude of factors. HNSCC is
      complicated because some of these cancers are clearly associated with HPV, while
      others have no viral involvement. Determining the pathways that are commonly
      altered in both types of HNSCC, as well as those that are unique to viral and
      nonviral tumors, is important for a basic understanding of how these cancers
      arise and progress and critical to the development of targeted therapies. In this
      work, we show that all HPV-associated tumors have increased expression of E2F
      target genes, indicating that the tumor suppressor function of Rb is blocked.
      Importantly, Rb is also inhibited in a subset of nonviral tumors, suggesting that
      mutations present in these cancers mimic the action of the HPV E6 and E7
      oncogenes.

PMID- 29359189
TI  - An Intracellular Ammonium Transporter Is Necessary for Replication,
      Differentiation, and Resistance to Starvation and Osmotic Stress in Trypanosoma
      cruzi.
AB  - Trypanosoma cruzi, the etiologic agent of Chagas disease, undergoes drastic
      metabolic changes when it transits between a vector and mammalian hosts. Amino
      acid catabolism leads to the production of ammonium (NH4+), which needs to be
      detoxified. However, T. cruzi does not possess a urea cycle, and it is unknown
      how intracellular levels of ammonium are controlled. In this work, we identified
      an intracellular ammonium transporter of T. cruzi (TcAMT) that localizes to
      acidic compartments (reservosomes, lysosomes). TcAMT has 11 transmembrane domains
      and possesses all conserved and functionally important amino acid residues that
      form the pore in other ammonium transporters. Functional expression in Xenopus
      oocytes followed by a two-electrode voltage clamp showed an inward current that
      is NH4+ dependent at a resting membrane potential (Vh ) lower than -120 mV and is
      not pH dependent, suggesting that TcAMT is not an NH4+/H+ cotransporter but an
      NH4+ or NH3/H+ transporter. Ablation of TcAMT by clustered regularly interspaced
      short palindromic repeat analysis with Cas9 (CRISPR-Cas9) resulted in significant
      defects in epimastigote and amastigote replication, differentiation, and
      resistance to starvation and osmotic stress. IMPORTANCETrypanosoma cruzi is an
      important human and animal pathogen and the etiologic agent of Chagas disease.
      The parasite undergoes drastic changes in its metabolism during its life cycle.
      Amino acid consumption becomes important in the infective stages and leads to the
      production of ammonia (NH3), which needs to be detoxified. We report here the
      identification of an ammonium (NH4+) transporter that localizes to acidic
      compartments and is important for replication, differentiation, and resistance to
      starvation and osmotic stress.

PMID- 29359191
TI  - Targeting Virulence in Staphylococcus aureus by Chemical Inhibition of the
      Accessory Gene Regulator System In Vivo.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) presents one of the most
      serious health concerns worldwide. The WHO labeled it as a "high-priority"
      pathogen in 2017, also citing the more recently emerged vancomycin-intermediate
      and -resistant strains. With the spread of antibiotic resistance due in large
      part to the selective pressure exerted by conventional antibiotics, the use of
      antivirulence strategies has been recurrently proposed as a promising therapeutic
      approach. In MRSA, virulence is chiefly controlled by quorum sensing (QS);
      inhibitors of QS are called quorum quenchers (QQ). In S. aureus, the majority of
      QS components are coded for by the accessory gene regulator (Agr) system.
      Although much work has been done to develop QQs against MRSA, only a few studies
      have progressed to in vivo models. Those studies include both prophylactic and
      curative models of infection as well as combination treatments with antibiotic.
      For most, high efficacy is seen at attenuating MRSA virulence and pathogenicity,
      with some studies showing effects such as synergy with antibiotics and antibiotic
      resensitization. This minireview aims to summarize and derive conclusions from
      the literature on the in vivo efficacy of QQ agents in MRSA infection models. In
      vitro data are also summarized to provide sufficient background on the hits
      discussed. On the whole, the reported in vivo effects of the reviewed QQs against
      MRSA represent positive progress at this early stage in drug development. Follow
      up studies that thoroughly examine in vitro and in vivo activity are needed to
      propel the field forward and set the stage for lead optimization.

PMID- 29359190
TI  - Dating the Cryptococcus gattii Dispersal to the North American Pacific Northwest.
AB  - The emergence of Cryptococcus gattii, previously regarded as a predominantly
      tropical pathogen, in the temperate climate of the North American Pacific
      Northwest (PNW) in 1999 prompted several questions. The most prevalent among
      these was the timing of the introduction of this pathogen to this novel
      environment. Here, we infer tip-dated timing estimates for the three clonal C.
      gattii populations observed in the PNW, VGIIa, VGIIb, and VGIIc, based on whole
      genome sequencing of 134 C. gattii isolates and using Bayesian evolutionary
      analysis by sampling trees (BEAST). We estimated the nucleotide substitution rate
      for each lineage (1.59 * 10-8, 1.59 * 10-8, and 2.70 * 10-8, respectively) to be
      an order of magnitude higher than common neutral fungal mutation rates (2.0 * 10
      9), indicating a microevolutionary rate (e.g., successive clonal generations in a
      laboratory) in comparison to a species' slower, macroevolutionary rate (e.g.,
      when using fossil records). The clonal nature of the PNW C. gattii emergence over
      a narrow number of years would therefore possibly explain our higher mutation
      rates. Our results suggest that the mean time to most recent common ancestor for
      all three sublineages occurred within the last 60 to 100 years. While the cause
      of C. gattii dispersal to the PNW is still unclear, our research estimates that
      the arrival is neither ancient nor very recent (i.e., <25 years ago), making a
      strong case for an anthropogenic introduction. IMPORTANCE The recent emergence of
      the pathogenic fungus Cryptococcus gattii in the Pacific Northwest (PNW) resulted
      in numerous investigations into the epidemiological and enzootic impacts, as well
      as multiple genomic explorations of the three primary molecular subtypes of the
      fungus that were discovered. These studies lead to the general conclusion that
      the subtypes identified likely emerged out of Brazil. Here, we conducted genomic
      dating analyses to determine the ages of the various lineages seen in the PNW and
      propose hypothetical causes for the dispersal events. Bayesian evolutionary
      analysis strongly suggests that these independent fungal populations in the PNW
      are all 60 to 100 years old, providing a timing that is subsequent to the opening
      of the Panama Canal, which allowed for more direct shipping between Brazil and
      the western North American coastline, a possible driving event for these fungal
      translocation events.

PMID- 29359193
TI  - Ecological Stability Properties of Microbial Communities Assessed by Flow
      Cytometry.
AB  - Natural microbial communities affect human life in countless ways, ranging from
      global biogeochemical cycles to the treatment of wastewater and health via the
      human microbiome. In order to probe, monitor, and eventually control these
      communities, fast detection and evaluation methods are required. In order to
      facilitate rapid community analysis and monitor a community's dynamic behavior
      with high resolution, we here apply community flow cytometry, which provides
      single-cell-based high-dimensional data characterizing communities with high
      acuity over time. To interpret time series data, we draw inspiration from
      macroecology, in which a rich set of concepts has been developed for describing
      population dynamics. We focus on the stability paradigm as a promising candidate
      to interpret such data in an intuitive and actionable way and present a rapid
      workflow to monitor stability properties of complex microbial ecosystems. Based
      on single-cell data, we compute the stability properties resistance, resilience,
      displacement speed, and elasticity. For resilience, we also introduce a method
      which can be implemented for continuous online community monitoring. The proposed
      workflow was tested in a long-term continuous reactor experiment employing both
      an artificial and a complex microbial community, which were exposed to identical
      short-term disturbances. The computed stability properties uncovered the superior
      stability of the complex community and demonstrated the global applicability of
      the protocol to any microbiome. The workflow is able to support high temporal
      sample densities below bacterial generation times. This may provide new
      opportunities to unravel unknown ecological paradigms of natural microbial
      communities, with applications to environmental, biotechnological, and health
      related microbiomes. IMPORTANCE Microbial communities drive many processes which
      affect human well-being directly, as in the human microbiome, or indirectly, as
      in natural environments or in biotechnological applications. Due to their
      complexity, their dynamics over time is difficult to monitor, and current
      sequence-based approaches are limited with respect to the temporal resolution.
      However, in order to eventually control microbial community dynamics, monitoring
      schemes of high temporal resolution are required. Flow cytometry provides single
      cell-based data in the required temporal resolution, and we here use such data to
      compute stability properties as easy to interpret univariate indicators of
      microbial community dynamics. Such monitoring tools will allow for a fast,
      continuous, and cost-effective screening of stability states of microbiomes.
      Applicable to various environments, including bioreactors, surface water, and the
      human body, it will contribute to the development of control schemes to
      manipulate microbial community structures and performances.

PMID- 29359192
TI  - Targeted Phenotypic Screening in Plasmodium falciparum and Toxoplasma gondii
      Reveals Novel Modes of Action of Medicines for Malaria Venture Malaria Box
      Molecules.
AB  - The Malaria Box collection includes 400 chemically diverse small molecules with
      documented potency against malaria parasite growth, but the underlying modes of
      action are largely unknown. Using complementary phenotypic screens against
      Plasmodium falciparum and Toxoplasma gondii, we report phenotype-specific hits
      based on inhibition of overall parasite growth, apicoplast segregation, and
      egress or host invasion, providing hitherto unavailable insights into the
      possible mechanisms affected. First, the Malaria Box library was screened against
      tachyzoite stage T. gondii and the half-maximal effective concentrations (EC50s)
      of molecules showing >=80% growth inhibition at 10 uM were determined. Comparison
      of the EC50s for T. gondii and P. falciparum identified a subset of 24 molecules
      with nanomolar potency against both parasites. Thirty molecules that failed to
      induce acute growth inhibition in T. gondii tachyzoites in a 2-day assay caused
      delayed parasite death upon extended exposure, with at least three molecules
      interfering with apicoplast segregation during daughter cell formation. Using
      flow cytometry and microscopy-based examinations, we prioritized 26 molecules
      with the potential to inhibit host cell egress/invasion during asexual
      developmental stages of P. falciparum. None of the inhibitors affected digestive
      vacuole integrity, ruling out a mechanism mediated by broadly specific protease
      inhibitor activity. Interestingly, five of the plasmodial egress inhibitors
      inhibited ionophore-induced egress of T. gondii tachyzoites. These findings
      highlight the advantage of comparative and targeted phenotypic screens in related
      species as a means to identify lead molecules with a conserved mode of action.
      Further work on target identification and mechanism analysis will facilitate the
      development of antiparasitic compounds with cross-species efficacy. IMPORTANCE
      The phylum Apicomplexa includes many human and animal pathogens, such as
      Plasmodium falciparum (human malaria) and Toxoplasma gondii (human and animal
      toxoplasmosis). Widespread resistance to current antimalarials and the lack of a
      commercial vaccine necessitate novel pharmacological interventions with distinct
      modes of action against malaria. For toxoplasmosis, new drugs to effectively
      eliminate tissue-dwelling latent cysts of the parasite are needed. The Malaria
      Box antimalarial collection, managed and distributed by the Medicines for Malaria
      Venture, includes molecules of novel chemical classes with proven antimalarial
      efficacy. Using targeted phenotypic assays of P. falciparum and T. gondii, we
      have identified a subset of the Malaria Box molecules as potent inhibitors of
      plastid segregation and parasite invasion and egress, thereby providing early
      insights into their probable mode of action. Five molecules that inhibit the
      egress of both parasites have been identified for further mechanistic studies.
      Thus, the approach we have used to identify novel molecules with defined modes of
      action in multiple parasites can expedite the development of pan-active
      antiparasitic agents.

PMID- 29359194
TI  - RNase III Domain of KREPB9 and KREPB10 Association with Editosomes in Trypanosoma
      brucei.
AB  - Editosomes are the multiprotein complexes that catalyze the insertion and
      deletion of uridines to create translatable mRNAs in the mitochondria of
      kinetoplastids. Recognition and cleavage of a broad diversity of RNA substrates
      in vivo require three functionally distinct RNase III-type endonucleases, as well
      as five additional editosome proteins that contain noncatalytic RNase III
      domains. RNase III domains have recently been identified in the editosome
      accessory proteins KREPB9 and KREPB10, suggesting a role related to editing
      endonuclease function. In this report, we definitively show that KREPB9 and
      KREPB10 are not essential in either bloodstream-form parasites (BF) or procyclic
      form parasites (PF) by creating null or conditional null cell lines. While
      preedited and edited transcripts are largely unaffected by the loss of KREPB9 in
      both PF and BF, loss of KREPB10 produces distinct responses in BF and PF. BF
      cells lacking KREPB10 also lack edited CYb, while PF cells have increased edited
      A6, RPS12, ND3, and COII after loss of KREPB10. We also demonstrate that mutation
      of the RNase III domain of either KREPB9 or KREPB10 results in decreased
      association with ~20S editosomes. Editosome interactions with KREPB9 and KREPB10
      are therefore mediated by the noncatalytic RNase III domain, consistent with a
      role in endonuclease specialization in Trypanosoma brucei. IMPORTANCETrypanosoma
      brucei is a protozoan parasite that causes African sleeping sickness. U
      insertion/deletion RNA editing in T. brucei generates mature mitochondrial mRNAs.
      Editing is essential for survival in mammalian hosts and tsetse fly vectors and
      is differentially regulated during the parasite life cycle. Three multiprotein
      "editosomes," typified by exclusive RNase III endonucleases that act at distinct
      sites, catalyze editing. Here, we show that editosome accessory proteins KREPB9
      and KREPB10 are not essential for mammalian blood- or insect-form parasite
      survival but have specific and differential effects on edited RNA abundance in
      different stages. We also characterize KREPB9 and KREPB10 noncatalytic RNase III
      domains and show they are essential for editosome association, potentially via
      dimerization with RNase III domains in other editosome proteins. This work
      enhances the understanding of distinct editosome and accessory protein functions,
      and thus differential editing, during the parasite life cycle and highlights the
      importance of RNase III domain interactions to editosome architecture.

PMID- 29359195
TI  - Machine Learning Leveraging Genomes from Metagenomes Identifies Influential
      Antibiotic Resistance Genes in the Infant Gut Microbiome.
AB  - Antibiotic resistance in pathogens is extensively studied, and yet little is
      known about how antibiotic resistance genes of typical gut bacteria influence
      microbiome dynamics. Here, we leveraged genomes from metagenomes to investigate
      how genes of the premature infant gut resistome correspond to the ability of
      bacteria to survive under certain environmental and clinical conditions. We found
      that formula feeding impacts the resistome. Random forest models corroborated by
      statistical tests revealed that the gut resistome of formula-fed infants is
      enriched in class D beta-lactamase genes. Interestingly, Clostridium difficile
      strains harboring this gene are at higher abundance in formula-fed infants than
      C. difficile strains lacking this gene. Organisms with genes for major
      facilitator superfamily drug efflux pumps have higher replication rates under all
      conditions, even in the absence of antibiotic therapy. Using a machine learning
      approach, we identified genes that are predictive of an organism's direction of
      change in relative abundance after administration of vancomycin and cephalosporin
      antibiotics. The most accurate results were obtained by reducing annotated
      genomic data to five principal components classified by boosted decision trees.
      Among the genes involved in predicting whether an organism increased in relative
      abundance after treatment are those that encode subclass B2 beta-lactamases and
      transcriptional regulators of vancomycin resistance. This demonstrates that
      machine learning applied to genome-resolved metagenomics data can identify key
      genes for survival after antibiotics treatment and predict how organisms in the
      gut microbiome will respond to antibiotic administration. IMPORTANCE The process
      of reconstructing genomes from environmental sequence data (genome-resolved
      metagenomics) allows unique insight into microbial systems. We apply this
      technique to investigate how the antibiotic resistance genes of bacteria affect
      their ability to flourish in the gut under various conditions. Our analysis
      reveals that strain-level selection in formula-fed infants drives enrichment of
      beta-lactamase genes in the gut resistome. Using genomes from metagenomes, we
      built a machine learning model to predict how organisms in the gut microbial
      community respond to perturbation by antibiotics. This may eventually have
      clinical applications.

PMID- 29359196
TI  - Magic Pools: Parallel Assessment of Transposon Delivery Vectors in Bacteria.
AB  - Transposon mutagenesis coupled to next-generation sequencing (TnSeq) is a
      powerful approach for discovering the functions of bacterial genes. However, the
      development of a suitable TnSeq strategy for a given bacterium can be costly and
      time-consuming. To meet this challenge, we describe a part-based strategy for
      constructing libraries of hundreds of transposon delivery vectors, which we term
      "magic pools." Within a magic pool, each transposon vector has a different
      combination of upstream sequences (promoters and ribosome binding sites) and
      antibiotic resistance markers as well as a random DNA barcode sequence, which
      allows the tracking of each vector during mutagenesis experiments. To identify an
      efficient vector for a given bacterium, we mutagenize it with a magic pool and
      sequence the resulting insertions; we then use this efficient vector to generate
      a large mutant library. We used the magic pool strategy to construct transposon
      mutant libraries in five genera of bacteria, including three genera of the phylum
      Bacteroidetes. IMPORTANCE Molecular genetics is indispensable for interrogating
      the physiology of bacteria. However, the development of a functional genetic
      system for any given bacterium can be time-consuming. Here, we present a
      streamlined approach for identifying an effective transposon mutagenesis system
      for a new bacterium. Our strategy first involves the construction of hundreds of
      different transposon vector variants, which we term a "magic pool." The efficacy
      of each vector in a magic pool is monitored in parallel using a unique DNA
      barcode that is introduced into each vector design. Using archived DNA "parts,"
      we next reassemble an effective vector for making a whole-genome transposon
      mutant library that is suitable for large-scale interrogation of gene function
      using competitive growth assays. Here, we demonstrate the utility of the magic
      pool system to make mutant libraries in five genera of bacteria.

PMID- 29359197
TI  - Prevalence and Source of Fecal and Oral Bacteria on Infant, Child, and Adult
      Hands.
AB  - Modern hygienic practices are applied to avoid exposure to pathogens that spread
      via fecal-oral transmission. Despite this, the gastrointestinal tract is quickly
      colonized by fecal microbes. The hands are an important vector for the
      transmission of microbes, but the frequency at which fecal and oral microbes
      exist on hands and the source of those microbes have not been extensively
      described. Using data from a previous study that characterized the fecal, oral,
      and skin microbiota from 73 families, we found a significant incidence of fecal
      and oral microbes on hands. Of palms, 48.9% had fecal signal and 67.2% had oral
      signal. Fecal, oral, and forehead microbes were tracked to family members and an
      individual's own palms far more often than to unrelated individuals and showed
      relationships with age, gender, and parental status. For instance, oral microbes
      that were specifically sourced to the same individual (oneself) were most common
      on infant palms; mothers had more infant-child-sourced and oral-sourced microbes
      on their palms than nonparents. Fecal microbes on palms more often sourced to
      members of the family than unrelated individuals, but more often to other members
      of the family than oneself. This study supports that the hands are an important
      vector for the transfer of fecal and oral microbes within families. IMPORTANCE
      Bacteria live all around us, and we are constantly exposed to them during our
      everyday lives. Modern standards of hygiene aim to limit exposure to fecal
      bacteria, and yet bacteria rapidly colonize the gut in early life and following
      antibacterial treatment. Exposures to fecal and oral microbes provide risk of
      disease, but are also necessary since commensal microbes play important roles in
      health. This work establishes that bacteria of both fecal and oral origins are
      commonly found on hands. It also establishes that the uniqueness of fecal and
      oral bacterial communities across people can allow for determination of the
      likely individual from whom the fecal and oral bacteria came. These techniques
      allow for understanding the hands as a vector for microbial transmission within
      families and across populations, which has important implications for public
      health.

PMID- 29359198
TI  - Beyond the Binary: Differences in Eating Disorder Prevalence by Gender Identity
      in a Transgender Sample.
AB  - Purpose: To investigate whether the prevalence of eating disorders (EDs) differs
      across diverse gender identity groups in a transgender sample. Methods: Secondary
      analysis of data from Project VOICE, a cross-sectional study of stress and health
      among 452 transgender adults (ages 18-75 years) residing in Massachusetts. Age
      adjusted logistic regression models were fit to compare the prevalence of self
      reported lifetime EDs in female-to-male (FTM), male-to-female (MTF), and gender
      nonconforming participants assigned male at birth (MBGNC) to gender-nonconforming
      participants assigned female at birth (FBGNC; referent). Results: The age
      adjusted odds of self-reported ED in MTF participants were 0.14 times the odds of
      self-reported ED in FBGNC participants (p=0.022). In FTM participants, the age
      adjusted odds of self-reported ED were 0.46 times the odds of self-reported ED in
      FBGNC participants, a marginally significant finding (p=0.068). No statistically
      significant differences in ED prevalence were found for MBGNC individuals.
      Conclusions: Gender nonconforming individuals assigned a female sex at birth
      appear to have heightened lifetime risk of EDs relative to MTF participants.
      Further research into specific biologic and psychosocial ED risk factors and
      gender-responsive intervention strategies are urgently needed. Training clinical
      providers and ensuring competency of treatment services beyond the gender binary
      will be vital to addressing this disparity.

PMID- 29359199
TI  - Project SARET: An interprofessional education (IPE) lens examines substance use
      disorders research education for health professional students.
AB  - The NIDA funded Substance Abuse Education, Research and Training (SARET) Program
      addresses the compelling need for health professionals prepared to engage in
      substance use disorders (SUD) research. The goal of this interprofessional
      project, structured by an Executive Committee of co-investigators from the
      disciplines of medicine, nursing, social work and dentistry, is to increase the
      skills of students from each discipline for interprofessional research
      collaboration and early career-development opportunities in SUD research. The
      development of web-based modules, interprofessional seminars and a model
      mentorship program were designed as well, for dissemination and evaluation by
      other health professional schools. The educational format is 6 interactive web
      based learning modules, providing an overview of core content on Substance Use
      Disorders (SUD), summer or year-long mentored research experiences with NIH
      funded researchers and small interprofessional seminars and site visits.
      Assessment consists of self-reported annual student learning outcomes and
      external editorial and advisory board project and curricular materials review.
      These reviews encourages the updating of materials and provide flexibility for
      participating "champions" at other schools who use the modules. Quantitative and
      qualitative outcomes of student research activities and data on dissemination of
      modules support the fit between project content and interprofessional teaching
      modalities. The learning modules are available without charge to individuals,
      students, faculty or health professional programs from the project's website.

PMID- 29359201
TI  - Morphological Development of Eggs, Larvae and Juveniles of the Far Eastern
      Catfish, Silurus asotus in Korea (Pisces: Siluridae).
AB  - This study was conducted to investigate egg development and larvae morphological
      development of catfish and to provide basic data to clarify the genetic
      relationship with Siluriformes fish. The mother fish that was used in this study
      was caught in the stream of Nakdong River in Uiseong-gun, Gyeongbuk. The
      temperature range of the breeding was 23.0-25.0C (mean 24.0+/-1.0C) and egg size
      was 1.62-1.70 mm (mean 1.66+/-0.05, n=30). Eggs of catfish began hatching at 54
      hours and 40 minutes after fertilization. Immediately after hatching, the total
      length of larvae was 3.60-3.65 mm (mean 3.62+/-0.03, n=5) and had an egg yolk
      without swimming ability. On the third day after hatching, the larvae at the
      medium stage was 8.00-8.65 mm (mean 8.32+/-0.45) in total length, and two pairs
      of whiskers formed around the mouth were elongated. On the 12th day after
      hatching, the larvae at the juvenile stage was 16.5-17.0 mm (mean 16.7+/-0.35) in
      total length, and the stem of each fin was in the range, and the juvenile at this
      period was morphologically similar to the mother fish.

PMID- 29359200
TI  - A Review of Mechanisms of Implantation.
AB  - Implantation is a highly organized process that involves an interaction between a
      receptive uterus and a competent blastocyst. In humans, natural fecundity
      suggests that the chance of conception per cycle is relatively low (~30%) and two
      third of lost pregnancies occur because of implantation failure. Defective
      implantation leads to adverse pregnancy outcomes including infertility,
      spontaneous miscarriage, intrauterine fetal growth restriction and preeclampsia.
      With use of advanced scientific technologies, gene expression analysis and
      genetically-engineered animal models have revealed critical cellular networks and
      molecular pathways. But, because of ethical restrictions and the lack of a
      mechanistic experiment, comprehensive steps in human implantation have still not
      been completely understood. This review primarily focuses on the recent advances
      in mechanisms of implantation. Because infertility is an emerging issue these
      days, gaining an understanding the molecular and hormonal signaling pathway will
      improve the outcome of natural pregnancy and assisted reproductive technology.

PMID- 29359202
TI  - Characterization of Tetraploid Somatic Cell Nuclear Transfer-Derived Human
      Embryonic Stem Cells.
AB  - Polyploidy is occurred by the process of endomitosis or cell fusion and usually
      represent terminally differentiated stage. Their effects on the developmental
      process were mainly investigated in the amphibian and fishes, and only observed
      in some rodents as mammalian model. Recently, we have established tetraploidy
      somatic cell nuclear transfer-derived human embryonic stem cells (SCNT-hESCs) and
      examined whether it could be available as a research model for the polyploidy
      cells existed in the human tissues. Two tetraploid hESC lines were artificially
      acquired by reintroduction of remained 1st polar body during the establishment of
      SCNT-hESC using MII oocytes obtained from female donors and dermal fibroblasts
      (DFB) from a 35-year-old adult male. These tetraploid SCNT-hESC lines (CHA-NT1
      and CHA-NT3) were identified by the cytogenetic genotyping (91, XXXY,-6, t[2:6] /
      92,XXXY,-12,+20) and have shown of indefinite proliferation, but slow speed when
      compared to euploid SCNT-hESCs. Using the eight Short Tendem Repeat (STR)
      markers, it was confirmed that both CHA-NT1 and CHA-NT3 lines contain both
      nuclear and oocyte donor genotypes. These hESCs expressed pluripotency markers
      and their embryoid bodies (EB) also expressed markers of the three embryonic germ
      layers and formed teratoma after transplantation into immune deficient mice. This
      study showed that tetraploidy does not affect the activities of proliferation and
      differentiation in SCNT-hESC. Therefore, tetraploid hESC lines established after
      SCNT procedure could be differentiated into various types of cells and could be
      an useful model for the study of the polyploidy cells in the tissues.

PMID- 29359203
TI  - Rare Undiagnosed Primary Amyloidosis Unmasked During Surgical Treatment of
      Primary Hyperparathyroidism: A Case Report.
AB  - Primary amyloidosis (PA) is a protein deposition disorder that presents with
      localized or multisystemic disease. The incidence is low in the general public,
      ranging from three to eight cases per million, and with nonspecific presenting
      symptoms typically occurring later in life. Due to late presentation, substantial
      and irreversible damage has usually already occurred by the time of the
      diagnosis. However, if inadvertent diagnosis occurs before irreversible damage
      has taken place, as it did in the following case, some patients may benefit from
      the disease-arresting treatment. A 70-year-old female with a history of
      obstructive sleep apnea, hypertension, and arthritis presented with worsening
      dysphagia and biochemically confirmed primary hyperparathyroidism (PHPT). Further
      workup demonstrated multinodular goiter with compressive symptoms and substernal
      extension, osteopenia, and discrepant parathyroid localization on imaging.
      Intraoperatively, markedly difficult dissection and obliteration of tissue planes
      were encountered. Extensive, diffuse amyloid deposition in both the normal and
      pathologic parathyroid glands and thyroid tissue on surgical pathology leads to
      subsequent fibril typing by mass spectrometry and leads to the diagnostic of
      primary amyloid light-chain (AL) amyloidosis (PA; lambda light chains).
      Subsequent workup for the underlying cause of the amyloid deposition revealed an
      immunoglobulin A monoclonal gammopathy of unknown significance. The surgical
      treatment of PHPT and compressive thyroid nodule unmasked an undiagnosed PA,
      allowing for early workup and monitoring of the progression of amyloidosis. The
      temporal comorbidity of PHPT and PA raises an interesting and, as yet, unanswered
      question regarding the pathophysiologic association between the two conditions.

PMID- 29359204
TI  - Analyzing Distributional Learning of Phonemic Categories in Unsupervised Deep
      Neural Networks.
AB  - Infants' speech perception adapts to the phonemic categories of their native
      language, a process assumed to be driven by the distributional properties of
      speech. This study investigates whether deep neural networks (DNNs), the current
      state-of-the-art in distributional feature learning, are capable of learning
      phoneme-like representations of speech in an unsupervised manner. We trained DNNs
      with unlabeled and labeled speech and analyzed the activations of each layer with
      respect to the phones in the input segments. The analyses reveal that the
      emergence of phonemic invariance in DNNs is dependent on the availability of
      phonemic labeling of the input during the training. No increased phonemic
      selectivity of the hidden layers was observed in the purely unsupervised networks
      despite successful learning of low-dimensional representations for speech. This
      suggests that additional learning constraints or more sophisticated models are
      needed to account for the emergence of phone-like categories in distributional
      learning operating on natural speech.

PMID- 29359206
TI  - Exploring oligomeric state of the serotonin1A receptor utilizing photobleaching
      image correlation spectroscopy: implications for receptor function.
AB  - The oligomerization of G protein-coupled receptors (GPCRs) represents an
      important process in GPCR function and drug discovery. We have addressed
      cholesterol-dependent oligomerization state of the serotonin1A receptor, a
      representative GPCR and an important drug target, utilizing photobleaching image
      correlation spectroscopy (pbICS). pbICS allows determination of oligomeric state
      of membrane receptors since change in cluster density upon photobleaching is
      dependent on the oligomeric state. Our results show that oligomeric state of the
      serotonin1A receptor is modulated by cell membrane cholesterol and a trimeric
      population of the receptor prevails in control (normal) cholesterol conditions.
      Interestingly, upon lowering membrane cholesterol, the predominant oligomeric
      population of the receptor changes to dimers. This is associated with an increase
      in specific ligand binding activity of the receptor, thereby implying a crucial
      role of receptor dimers in ligand binding activity. Upon cholesterol
      replenishment, the distribution of receptor oligomers is further changed such
      that the trimers become the major population, with a concomitant restoration of
      ligand binding activity to the control level. These results demonstrate the
      utility of pbICS in monitoring oligomeric states of membrane receptors in
      general, and the cholesterol-dependent oligomeric state of the serotonin1A
      receptor in particular. We envision that functional correlates of oligomeric
      states of GPCRs could provide better understanding of GPCR function in health and
      disease, and help design better therapeutic strategies.

PMID- 29359205
TI  - pH-Mediated molecular differentiation for fluorimetric quantification of
      chemotherapeutic drugs in human plasma.
AB  - At present, drug dosage is based on standardised approaches that disregard
      pharmakokinetic differences between patients and lead to non-optimal efficacy and
      unnecessary side effects. In this work, we demonstrate the potential of pH
      mediated fluorescence spectroscopy for therapeutic drug monitoring in complex
      media. We apply this principle to the simultaneous quantification of the
      chemotherapeutic prodrug Irinotecan and its active metabolite SN-38 from human
      plasma across the clinically relevant concentration range, i.e. from micromolar
      to nanomolar at molar ratios of up to 30 : 1.

PMID- 29359207
TI  - Two-dimensional electronic spectroscopy as a tool for tracking molecular
      conformations in DNA/RNA aggregates.
AB  - A computational strategy to simulate two-dimensional electronic spectra (2DES) is
      introduced, which allows us to analyse ground state dynamics and to sample and
      measure different conformations attained by flexible molecular systems in
      solution. An explicit mixed quantum mechanics/molecular mechanics (QM/MM)
      approach is employed for the evaluation of the necessary electronic excited state
      energies and transition dipole moments. The method is applied towards a study of
      the highly flexible water-solvated adenine-adenine monophosphate (ApA), a system
      featuring two interacting adenine moieties that display various intermolecular
      arrangements, known to deeply affect their photochemical outcome. Molecular
      dynamics simulations and cluster analysis have been used to select the molecular
      conformations, reducing the complexity of the flexible ApA conformational space.
      By using our sum-over-states (SOS) approach to obtain the 2DES spectra for each
      of these selected conformations, we can discern spectral changes and relate them
      to specific nuclear arrangements: close lying pi-stacked bases exhibit a
      splitting of their respective 1La signal traces; T-stacked bases exhibit the
      appearance of charge transfer states in the low-energy Vis probing window while
      displaying no 1La splitting, being particularly favoured when promoting amino to
      5-ring interactions; unstacked and distant adenine moieties exhibit signals
      similar to those of the adenine monomer, as is expected for non-interacting
      nucleobases. 2DES maps reveal the spectral fingerprints associated with specific
      molecular conformations, and are thus a promising option to enable their
      quantitative spectroscopic detection beyond standard 1D pump-probe techniques.
      This is expected to aid the understanding of how nucleobase aggregation controls
      and modulates the photostability and photo-damage of extended DNA/RNA systems.

PMID- 29359208
TI  - Photoinduced formation mechanism of the thymine-thymine (6-4) adduct in DNA; a
      QM(CASPT2//CASSCF):MM(AMBER) study.
AB  - The UVB-induced photomechanism leading the carbonyl group of a thymine nucleobase
      to react with the carbon-carbon double bond of a consecutive thymine nucleobase
      in a DNA strand to form the thymine-thymine (6-4) photodamage adduct remains
      poorly understood. Key questions remain unanswered, concerning both the intrinsic
      features of the photoreaction (such as the contribution (or not) of triplet
      states, the nature of the involved states and the time-scale of the photoprocess)
      and the role played by the non-reactive surroundings of the two reactive
      pyrimidine nucleobases (such as the nature of the flanked nucleobases and the
      flexibility of the whole DNA molecule). A small number of theoretical studies
      have been carried out on the title photoreaction, most of which have used reduced
      model systems of DNA, consequently neglecting potential key parameters for the
      photoreaction such as the constraints due to the double strain structure and the
      presence of paired and stacked nucleobases. In the present contribution the
      photoactivation step of the title reaction has been studied in a DNA system, and
      in particular for a specific DNA hairpin for which the quantum yield of
      photodamage formation has been recently experimentally measured. The reaction has
      been characterized by carrying out high-level QM/MM computations, combining the
      CASPT2//CASSCF approach for the study of the reactive part (i.e. the two thymine
      molecules) with an MM-Amber treatment of the surrounding environment. The
      possibility of a reaction path along both the singlet and triplet manifolds has
      been characterized, the nature of the reactive states has been analyzed, and the
      role played by the flexibility of the whole system, which in turn determines the
      initial accessible geometrical conformations, has been evaluated, thus
      substantially contributing towards the elucidation of the photoreaction
      mechanism. On the basis of the obtained results, it can be observed that a charge
      transfer state can decay from a pro-reactive initial structure towards a region
      of energy degeneracy with the ground state, from which the subsequent decay along
      the ground state hypersurface can lead to the photoreaction.

PMID- 29359209
TI  - Purification, characterization and anti-fatigue activity of polysaccharide
      fractions from okra (Abelmoschus esculentus (L.) Moench).
AB  - The aim of this study was to investigate the anti-fatigue activity of
      polysaccharide fractions from Abelmoschus esculentus (L.) Moench (AE) in mice.
      After crude polysaccharide (CAEP) was extracted from AE and purified by DEAE
      cellulose-52 column, two polysaccharide fractions (AEP-1 and AEP-2) were
      obtained. The structural analysis suggested that AEP-1 and AEP-2 were a RG-I
      polysaccharide and an AG-II polysaccharide, respectively. According to the
      results of the weight-loaded swimming test, compared with the negative control
      group, the CAEP, AEP-1 and AEP-2 treatment groups could prolong the swimming
      time, decrease serum urea nitrogen (SUN) and blood lactic acid (BLA), and
      increase hepatic glycogen (HG) and muscle glycogen (MG), which indicated that
      okra polysaccharides have an effective anti-fatigue activity. Furthermore, our
      study exhibited the anti-fatigue mechanism of okra polysaccharide was correlated
      with retarding the accumulation of creatine kinase (CK) and lactate dehydrogenase
      (LDH) in serum, and enhancing succinate dehydrogenase (SDH), adenosine
      triphosphate (ATP) and adenosine triphosphatase (ATPase) levels. In addition, the
      anti-fatigue activity of AEP-1 was stronger than that of AEP-2, and significantly
      better than that of CAEP. Therefore, AEP-1 and AEP-2 may be the main active anti
      fatigue functional substances of AE.

PMID- 29359210
TI  - Elucidating the structure of a high-spin sigma-phenyliron(iii) species in a live
      FeCl3-PhZnCl reaction system.
AB  - Environmentally benign iron catalysts promote a wide variety of chemical
      transformations; however, insight into the mechanism and active intermediates is
      far from satisfactory, and the main difficulties lie in directly "seeing" the
      active species under "live" catalytic conditions. Herein, an unknown sextet
      Ph(THF)FeCl2 species was well-characterized in a live FeCl3-PhZnCl reaction
      system for the first time by Raman, in situ IR, electron paramagnetic resonance
      (EPR), X-ray absorption spectroscopic (XAS) and density functional theory (DFT)
      calculations. This work provides insight into the structure and reactivity of
      catalytically relevant sigma-aryliron(iii) species, and shall provide useful
      guidelines for understanding iron chemistry.

PMID- 29359211
TI  - Correction: Quantitative profiling of carbonyl metabolites directly in crude
      biological extracts using chemoselective tagging and nanoESI-FTMS.
AB  - Correction for 'Quantitative profiling of carbonyl metabolites directly in crude
      biological extracts using chemoselective tagging and nanoESI-FTMS' by Pan Deng,
      et al., Analyst, 2018, 143, 311-322.

PMID- 29359212
TI  - Production of monodisperse drops from viscous fluids.
AB  - Drops are often used as picoliter-sized reaction vessels, for example for high
      throughput screening assays, or as templates to produce particles of controlled
      sizes and compositions. Many of these applications require close control over the
      size of drops, which can be achieved if they are produced with microfluidics.
      However, this tight size control comes at the expense of the throughput that is
      too low for many materials science and almost all industrial applications. To
      overcome this limitation, different parallelized microfluidic devices have been
      reported. These devices typically operate at high throughputs if the viscosity of
      the inner fluid is low. However, fluids that are processed into particles often
      contain high concentrations of reagents and therefore are rather viscous. We
      report a microfluidic device containing parallelized triangular nozzles with
      rectangular cross-sections that can process solutions with viscosities up to 155
      mPa s into drops of well-defined sizes and narrow size distributions at
      significantly higher throughputs than what could be achieved previously. The
      increased throughput is enabled by the introduction of shunt channels: each
      nozzle is intersected by shunt channels that facilitate the backflow of the outer
      phase, thereby increasing the critical rate at which the fluid flow transitions
      from the dripping into the jetting regime. These modified nozzles open up new
      possibilities to employ drops made of viscous fluids as templates to produce
      particles with well-defined sizes for applications that require larger
      quantities.

PMID- 29359213
TI  - Halide encapsulation by dicarboxylate oxido-vanadium cage complexes.
AB  - Compounds [Bu4N]2[V8O16(oda)4?2Cl], 1, [Bu4N]2[V8O16(glut)4?2Cl], 2, and
      [Bu4N][V4O8(glut)2?F], 3, (oda = oxydiacetate, O(CH2COO)22-; glut = glutarate,
      CH2(CH2COO)22-) were obtained by a stepwise reaction of in situ prepared
      [Bu4N]VO3 with HCl (or HF for 3) and then with the dicarboxylic acid X(CH2COOH)2
      (X = O and CH2), under appropriate reaction conditions. Multinuclear magnetic
      resonance (1H, 13C{1H}, 35Cl, 19F and 51V), electrochemical studies, X-ray
      structural determinations (single crystal and powder), thermogravimetric analyses
      (TGA) and Density Functional Theory (DFT) calculations were employed to
      characterise these polyoxovanadate complexes 1-3. They included encapsulated
      halide anions, two chloride ions in 1 and 2 and one fluoride ion in 3, where the
      shape and dimensions of the cage were governed by the halide size. The
      stabilizing template effect of the chloride ion towards the bowl-shaped
      [V4O8(OOCR)4] fragment (i.e. the half part of 1 and 2), containing a crown-shaped
      {V4O8} subunit, or that of the fluoride ion towards the planar {V4O8} moiety in
      3, was definitively demonstrated by DFT calculations. The HOMO composition of 1
      prompted us to study the possible oxidation of the two encapsulated chloride ions
      toward a chlorine molecule. The electrochemical behaviors of 1-3 were thus
      investigated. However, the chlorine molecule in the model [V8O16(oda)4?(Cl2)],
      6c, was not capable to stabilise the polyoxovanadate cage [V8O16(oda)4], 4c,
      according to DFT calculations.

PMID- 29359215
TI  - Electron transport in polycyclic aromatic hydrocarbons/boron nitride hybrid
      structures: density functional theory combined with the nonequilibrium Green's
      function.
AB  - We investigate the electronic transport properties of two types of junction based
      on single polyaromatic hydrocarbons (PAHs) and PAHs embedded in boron nitride (h
      BN) nanoribbons, using nonequilibrium Green's functions (NEGF) and density
      functional theory (DFT). In the PAH junctions, a Fano resonance line shape at the
      Fermi energy in the transport feature can be clearly seen. In hybrid junctions,
      structural asymmetries enable interactions between the electronic states, leading
      to observation of interface-based transport. Our findings reveal that the
      interface of PAH/h-BN strongly affects the transport properties of the
      structures.

PMID- 29359217
TI  - Chiral self-assembly of fullerene clusters on CT-DNA templates.
AB  - Herein we discuss the differential interaction of three monosubstituted fullerene
      derivatives possessing pyridinium, aniline or phenothiazine end groups (F-Py, F
      An and F-PTz, respectively) with calf thymus DNA (CT-DNA), probed via
      spectroscopic and imaging techniques. The pyridinium derivative, F-Py becomes
      molecularly dissolved in 10% DMSO-PBS and interacts with CT-DNA via groove
      binding and electrostatic interactions, leading to the initial condensation of CT
      DNA into micrometer sized aggregates and subsequent precipitation. On the other
      hand, the aniline derivative F-An, which is reported to form nanoclusters of 3-5
      nm size, interacts with DNA through ordered, chiral assemblies on the CT-DNA
      template, thus perturbing the highly networked structure of CT-DNA to form
      nanonetworks, which eventually transform into condensed aggregates. The binding
      interactions between CT-DNA and F-An nanoclusters were established via UV-Vis,
      AFM and TEM analysis, and the chiral nature of the fullerene nanocluster
      assemblies on CT-DNA was confirmed by the presence of induced circular dichroism
      that was exhibited around the 250-370 nm region, corresponding to F-An
      nanocluster absorption. In contrast, the phenothiazine derivative F-PTz, which
      forms larger nanoclusters of ~70 nm size in 10% DMSO-PBS, exhibited only weak
      interactions with CT-DNA without affecting its network structure. These results
      demonstrate the role of the hydrophobic-hydrophilic balance in the design of DNA
      interacting fullerene derivatives by controlling their cluster size and
      interactions with CT-DNA, and are significant in applications such as DNA
      condensation, gene delivery and dimension controlled nanomaterial fabrication.

PMID- 29359218
TI  - Precisely controlled synthesis of alpha-/beta-MnO2 materials by adding Zn(acac)2
      as a phase transformation-inducing agent.
AB  - In this paper, we present an approach for the precisely controlled phase
      transformation of MnO2 in order to synthesise different compositions of alpha
      /beta-MnO2 materials, by adding a trace amount of Zn(acac)2 as the phase
      transformation-inducing agent in a hydrothermal reaction. The single-atomic
      dispersion of Zn might reduce the barrier of phase transformation of delta-MnO2
      to beta-MnO2. The ratio of the Zn species present in the single-atomic
      dispersions and nanoclusters might dominate the generation of alpha-MnO2 and beta
      MnO2. The results of the oxygen reduction reactions indicate that the MnO2
      materials have potential applications as promising catalysts in electrochemical
      catalysis.

PMID- 29359219
TI  - Making organoruthenium complexes of 8-hydroxyquinolines more hydrophilic: impact
      of a novel l-phenylalanine-derived arene ligand on the biological activity.
AB  - Ru(arene) compounds have many desirable features making them promising candidates
      for further development in anticancer drug research. While a lot of emphasis has
      been placed on the modification of the ancillary ligands, there are not many
      examples of arene ligands bearing functional groups. Herein, we report the
      preparation of [Ru(arene)(8-oxyquinolinato)Cl] complexes with the arene being a
      protected form of the amino acid l-phenylalanine and 8-oxyquinolinato ligand
      substituted with halogens. With this approach we aimed to alter the
      pharmacological properties of the complexes and address issues with the aqueous
      solubility of the analogous p-cymene complexes. The complexes were shown to be
      stable in DMSO and water and reacted readily with l-histidine and 9-ethylguanine
      as protein and DNA models, respectively. Assaying the antiproliferative activity
      in cancer cells gave IC50 values in the low MUM range. While the lipophilicity of
      the p-cymene analogues correlated well with their in vitro cytotoxicity, the
      potency of the complexes with the l-phenylalanine-derived arene was independent
      of lipophilicity.

PMID- 29359220
TI  - Synthesis of aryl alpha,alpha-difluoroethyl thioethers a novel structure motif in
      organic chemistry, and extending to aryl alpha,alpha-difluoro oxyethers.
AB  - A method for the preparation of aryl alpha,alpha-difluoroethyl thioethers
      (ArSCF2CH3) is reported and the synthesis approach is extended to aryl
      alpha,alpha-difluoroethyl oxygen ethers. Selected building blocks are further
      elaborated in cross-coupling reactions and are incorporated into analogues of
      established trifluoromethyl ether drugs. Conformations are explored and log P
      studies of these motifs indicate that they are significantly more polar than
      their trifluoromethyl ether analogues rendering them attractive for bioactives
      discovery.

PMID- 29359222
TI  - Bioactive compounds and antioxidant capacity of extruded snack-type products
      developed from novel formulations of lentil and nutritional yeast flours.
AB  - Pulses are well known to be gluten-free functional foods that provide a rich
      source of nutritional and healthy compounds with antioxidant-promoting activity.
      In the present study, the bioactive compounds, dietary fibre, arabinoxylans,
      individual phenolic compounds and tocopherols, were evaluated in different lentil
      flours (raw and extruded at 140 and 160  degrees C) formulated with nutritional
      yeasts, along with the changes induced by the extrusion process. The total
      dietary fibre and arabinoxylan content significantly (p < 0.05) increased after
      the extrusion process while a significant decrease of all tocopherol isoforms was
      also observed. Catechin, caffeic, kaempferol and quercetin derivatives were
      identified in the raw and extruded lentil flours. The decreases of total phenolic
      and individual phenolic compounds were directly related to the extrusion
      temperature; total phenolics and catechin hexoside exhibited a larger decrease in
      the lentil flours formulated with higher content of nutritional yeast (12 and
      16%). The antioxidant activity results, determined using different assays,
      reflected the important effect of extrusion processing and food ingredients.

PMID- 29359223
TI  - Optical backbone-sidechain charge transfer transitions in proteins sensitive to
      secondary structure and modifications.
AB  - The absorption of light by proteins can induce charge transfer (CT) transitions
      in the UV-visible range of the electromagnetic spectrum. Metal-ligand complexes
      or active site prosthetic groups which absorb in the visible region exhibit
      prominent CT transitions. Furthermore, the protein backbone also exhibits CT
      transitions in the far UV range. In this manuscript, we present a detailed
      computational study of new near UV-visible CT transitions that involve amino
      acids with charged side chains. Specifically, using time dependent density
      functional theory calculations, we examine the absorption spectra of naturally
      charged amino acids (Lys, Glu, Arg, Asp and His), extracted from solution phase
      protein structures generated by classical molecular dynamics simulations, and
      phosphorylated amino acids (Tyr, Thr and Ser) from experimentally determined
      protein structures. We show that amino acids with charged sidechains present a
      directed electronic donor-bridge-acceptor paradigm, with the lowest energy
      optical excitations demonstrating peptide backbone-sidechain charge separations.
      The UV-visible spectral range of the backbone-sidechain CT transitions is
      determined by the chemical nature of the donor, bridge and acceptor groups within
      each amino acid, amino acid conformation and the protein secondary structure
      where the amino acids are located. Photoinduced CT occurs in opposite directions
      for the anionic and cationic amino acids along the ground state dipole moment
      vector for the chromophores. We find that photoinduced charge separation is more
      facile for the anionic amino acids (Asp, Glu, pSer, pThr and pTyr) relative to
      that for the cationic amino acids (Lys, Arg and Hsp). Our results provide a
      foundation for the development of spectroscopic markers based on the recently
      proposed Protein Charge Transfer Spectra (ProCharTS) which are relevant for the
      study of DNA-binding or intrinsically disordered proteins that are rich in
      charged amino acids.

PMID- 29359224
TI  - Coffee consumption promotes skeletal muscle hypertrophy and myoblast
      differentiation.
AB  - Coffee is a widely consumed beverage worldwide and is believed to help prevent
      the occurrence of various chronic diseases. However, the effect of coffee on
      skeletal muscle hypertrophy, differentiation and the mechanisms of action
      responsible have remained unclear. To investigate the effect of coffee on
      skeletal muscle hypertrophy, mice were fed a normal diet or a normal diet
      supplemented with 0.3% coffee or 1% coffee. Coffee supplementation was observed
      to increase skeletal muscle hypertrophy, while simultaneously upregulating
      protein expression of total MHC, MHC2A, and MHC2B in quadricep muscle. Myostatin
      expression was also attenuated, and IGF1 was upregulated with subsequent
      phosphorylation of Akt and mTOR, while AMPK phosphorylation was attenuated.
      Coffee also increased the grip strength and PGC-1alpha protein expression, and
      decreased the expressions of TGF-beta and myostatin in tricep muscle. Coffee
      activated the MKK3/6-p38 pathway and upregulated PGC-1alpha, which may play a
      role in promoting myogenic differentiation and myogenin expression in C2C12
      cells. These results suggest that coffee increases skeletal muscle function and
      hypertrophy by regulating the TGF-beta/myostatin - Akt - mTORC1.

PMID- 29359225
TI  - Emerging investigator series: geochemistry of trace elements associated with Fe
      and Mn nodules in the sediment of limed boreal lakes.
AB  - Thousands of boreal lakes were limed for decades in Scandinavia to counteract the
      effect of anthropogenic acidification. We measured the concentrations of alkali
      earth metals (Ca, Mg, Ba), metals (Mn, Fe, Al, Co, Cd, Pb, Zn), metalloids (As,
      Mo) and phosphorus (P) in 165 surface sediment samples from 17 limed lakes, as
      well as the sediment column and porewater of two lakes chosen from this set. We
      report that formation of ferromanganese nodules is widespread in limed lakes, and
      that those nodules are enriched in trace elements, reaching for example 11 500,
      908 and 40 MUg g-1 for Ba, Mo and As, respectively. Nodules are more abundant
      between the littoral and the profundal zones. Intense redox cycling of Fe and Mn
      at the sediment-water interface has redistributed trace elements in the sediment
      column. Ba, Co, Mo, Pb and Zn partitioned with Mn (oxy)hydroxides and As and P
      with Fe (oxy)hydroxides. Fe, Mo, Co and As remobilized to the porewater also
      diffused downward and were likely sequestrated with sulfides. We conclude that
      the diagenetic redistribution and partitioning of trace elements onto Fe-Mn
      nodules, rather than direct inputs from liming, is the cause of the elevated
      trace element burden in surface sediments.

PMID- 29359226
TI  - Chemical language and warfare of bacterial natural products in bacteria-nematode
      insect interactions.
AB  - Covering: up to November 2017 Organismic interaction is one of the fundamental
      principles for survival in any ecosystem. Today, numerous examples show the
      interaction between microorganisms like bacteria and higher eukaryotes that can
      be anything between mutualistic to parasitic/pathogenic symbioses. There is also
      increasing evidence that microorganisms are used by higher eukaryotes not only
      for the supply of essential factors like vitamins but also as biological weapons
      to protect themselves or to kill other organisms. Excellent examples for such
      systems are entomopathogenic nematodes of the genera Heterorhabditis and
      Steinernema that live in mutualistic symbiosis with bacteria of the genera
      Photorhabdus and Xenorhabdus, respectively. Although these systems have been used
      successfully in organic farming on an industrial scale, it was only shown during
      the last 15 years that several different natural products (NPs) produced by the
      bacteria play key roles in the complex life cycle of the bacterial symbionts, the
      nematode host and the insect prey that is killed by and provides nutrients for
      the nematode-bacteria pair. Since the bacteria can switch from mutualistic to
      pathogenic lifestyle, interacting with two different types of higher eukaryotes,
      and since the full system with all players can be established in the lab, they
      are promising model systems to elucidate the natural function of microbial NPs.
      This review summarizes the current knowledge as well as open questions for NPs
      from Photorhabdus and Xenorhabdus and tries to assign their roles in the
      tritrophic relationship.

PMID- 29359227
TI  - Oral declines and mastication deficiencies cause alteration of food bolus
      properties.
AB  - In the elderly, masticatory function often presents failure in certain oral tasks
      due to impairment such as decline in muscular force, jaw or tongue motility,
      neuro-muscular coordination, tooth damage, malocclusion and saliva production.
      Great disparity is observed in the various and potentially cumulative oral
      declines that occur with ageing. Such difficulties may have an impact on food
      consumption and nutritional status. To obtain better understanding of the
      consequences of several oral deficiencies, a series of swallowable boluses were
      prepared in vitro with the AM2 masticator apparatus with normal and deficient
      programming. Physiological normal mastication (NM) was simulated using in vivo
      data from healthy subjects. Chewing deficiencies were reproduced by alteration of
      NM programming to perform different levels and combinations of force loss, lack
      of saliva and decrease in the motility of oral elements. Poultry meatballs were
      used as test-food. Particle size distribution in the food bolus was measured by
      sieving and rheological features (hardness, cohesiveness and elasticity) were
      assessed with a TPA test. Compared to the NM outcome, significant and gradual
      deterioration of the food bolus was observed and associated with alteration in
      force, saliva and motility. Combinations of several failures led to greater or
      cumulative deficiencies in swallowable bolus properties. For the elderly
      presenting a high prevalence of various oral injuries, tailoring textured food
      cannot be ignored as a solution for remedying deficiencies and favoring the
      formation of a safe-swallowable bolus, which is an essential vector of nutrients.
      Knowing the impacts of oral injuries on the food bolus is obviously a requisite
      for developing diet strategies, including nutritional items for specific
      populations.

PMID- 29359230
TI  - Optofluidic gutter oil discrimination based on a hybrid-waveguide coupler in
      fibre.
AB  - Discriminating edible oils from gutter oils has significance in food safety, as
      illegal gutter oils cannot meet a variety of criteria such as the acid value,
      peroxide value and quality. To discriminate these illegal cooking oils, we
      propose an ultrasensitive optofluidic detection method based on a hybrid
      waveguide coupler. Prior to the straight waveguide inscription in the cladding of
      the silica tube using a femtosecond laser, a section of coreless fibre is firstly
      spliced with the ST to supply a platform for the inscription of an S-band
      waveguide. Then a pair of microfluidic channels are ablated on the ST using the
      fs laser to enable liquid analytes to flow in and out of the air channel. In the
      transmission spectrum, a unique resonant loss dip can be observed, which is
      produced by coupling the light from the laser inscribed waveguide to the liquid
      core when the phase-matching condition is met. This hybrid-waveguide coupler with
      a simplified structure realizes dynamic optofluidic refractive index sensing with
      an ultrahigh sensitivity of -112 743 nm RIU-1, a detection limit of 2.08 * 10-5
      RIU and a refractive index detection range from 1.4591 to 1.4622. This novel
      method can be used for food safety detection, specifically, for the
      discrimination of gutter oils.

PMID- 29359231
TI  - Temporal trends and regional disparity in rheumatoid arthritis and gout
      hospitalizations in Sweden, 1998-2015.
AB  - Hospitalization is an important component of rheumatoid arthritis (RA) and gout
      economic burden. This study aimed to assess temporal trends and regional
      disparities in RA and gout hospitalizations among people aged >= 20 years in
      Sweden during 1998-2015. Data on hospital admissions with a principal diagnosis
      of RA or gout were collected from the National Patient Register. Age-standardized
      hospitalization rates (ASHRs) were calculated by means of direct standardization.
      The absolute and relative regional disparities were assessed. The temporal trends
      in ASHR and proportion of RA and gout hospitalizations from all and
      musculoskeletal disorders hospitalizations were analyzed using joinpoint
      regression. Between 1998-2000 and 2013-2015, the ASHR for RA declined by 78.9%
      from 109.9 to 23.2 per 100,000 Swedish adults, while it almost doubled for gout
      (from 10.5 to 20.8 per 100,000 Swedish adults). While in 1998-2000, RA
      hospitalizations were 10.3 times more frequent than gout (0.54 vs 0.05% of all
      hospitalizations), this ratio declined to 1.1 in 2013-2015 (0.13 vs 0.11% of all
      hospitalizations). The joinpoint regression revealed that, on average, the ASHR
      for RA declined by 10.2% (95% CI: 9.3-11.1) per year whereas for gout, it rose by
      4.3% (3.2-5.4) per year during 1998-2015. While the relative regional disparities
      were stable, the absolute regional disparity declined for RA and increased for
      gout over the study period. While substantial decline in RA hospitalization is
      encouraging, the substantial rise in gout hospitalization is of concern,
      reflecting potential increase in prevalence of gout and suboptimal management of
      the disease.

PMID- 29359232
TI  - Nano-silver modifies the vase life of cut herbaceous peony (Paeonia lactiflora
      Pall.) flowers.
AB  - Herbaceous peony (Paeonia lactiflora Pall.) is a popular high-grade cut flower
      because of higher ornamental value. However, its short flowering time severely
      restricts the production and application of cut P. lactiflora flowers. In this
      study, nano-silver (NS) was applied to prolong the vase life of cut P. lactiflora
      flowers. Under the NS treatment, related physiological indices including relative
      electrical conductivity (REC), malondialdehyde (MDA), superoxide anion free
      radical (O2.-), hydrogen peroxide (H2O2) and free proline contents, and
      protective enzyme activities including superoxide dismutase (SOD), peroxidase
      (POD) and ascorbic acid peroxidase (APX) all increased in cut P. lactiflora
      flowers except soluble protein. Meanwhile, NS treatment increased relative water
      uptake (RWU) and Ag+ distribution. Moreover, the observation of microstructures
      indicated that the stem-ends without NS treatment were blocked by microbes which
      were identified as Alternaria sp. and Phoma sp., and NS effectively inhibited
      their growth by antibacterial efficacy observation. Additionally, three aquaporin
      genes (AQPs) including two plasma membrane intrinsic protein genes (PlPIP1;2,
      PlPIP2;1) and one NOD26-like intrinsic protein gene (PlNIP) were isolated,
      PlPIP1;2, and PlPIP2;1 that were induced by NS treatment took common effects on
      maintaining the water balance of cut P. lactiflora flowers. Consequently, the
      vase life of cut P. lactiflora flowers was prolonged and flower fresh weight
      together with flower diameter was well kept because of these above factors. These
      results would provide a theoretical basis for prolonging the vase life and
      improving the ornamental quality of cut P. lactiflora flowers with NS
      application.

PMID- 29359233
TI  - Investigating Psychosocial Causes of the Tendency for Facial Cosmetic Surgery.
AB  - INTRODUCTION: Despite the importance of cosmetic surgery in improving body image
      and promoting individuals' physical and mental health, it is accompanied with
      some physical, mental, and economic problems, because it is an invasive
      procedure. Considering such extensive consequences and given the rising demand
      for performing such surgeries, it is essential to consider programs for reducing
      such requests. The present study aimed to investigate the psychosocial causes of
      the tendency for facial cosmetic surgery in patients referred to medical centers
      in Ahvaz in 2016-2017. MATERIALS AND METHODS: This study was conducted on 385
      facial cosmetic surgery applicants referred to medical centers in Ahvaz and were
      selected using a sequential non-probability sampling method. The data collection
      tool was a questionnaire divided into two sections namely: (1) demographic
      questions and (2) a questionnaire on the psychosocial causes of the tendency for
      facial cosmetic surgery. RESULTS: The mean scores of the psychological and social
      causes of the tendency for facial cosmetic surgery were 4.46 (SD = 1.67) and 3.44
      (SD = 2.57), respectively. "Being interested in being beautiful" was the most
      frequent positive response of the participants regarding the cause of tending to
      undergo facial cosmetic surgery (88.6%) and the least frequent response was
      estimated to be 35.1% for the "inappropriate psychological state" cause.
      CONCLUSION: The results of this study showed that psychological factors affected
      the participants' tendency for facial cosmetic surgery more than social factors.
      Determining and identifying such psychological pressures and providing individual
      training and psychological support can prevent individuals from undergoing facial
      cosmetic surgery. LEVEL OF EVIDENCE IV: This journal requires that authors assign
      a level of evidence to each article. For a full description of these Evidence
      Based Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 29359234
TI  - Analysis of Symmetry Stability Following Implant-Based Breast Reconstruction and
      Contralateral Management in 582 Patients with Long-Term Outcomes.
AB  - INTRODUCTION: This study aimed to analyse the long-term outcomes following breast
      reconstruction and contralateral management to evaluate the stability of breast
      symmetry and patient satisfaction. MATERIALS AND METHODS: The study population
      consisted of women who had undergone implant-based monolateral breast
      reconstruction and contralateral management. Patients answered the BREAST-Q
      reconstruction module. Two reviewers analysed the post-operative outcomes of the
      patients included and compiled the Kroll Scale. Patients were divided into three
      groups: implant-based contralateral management, breast reduction and mastopexy.
      The Fisher's exact test was applied to the results. RESULTS: From the BREAST-Q
      analysis, the group of patients undergoing contralateral breast augmentation
      achieved significantly better results regarding the ability to wear clothing (p ?
      0.001), symmetry (p ? 0.001), psychosocial well-being (p ? 0.001) and physical
      well-being (p ? 0.001). From the analysis of the Kroll Scale, the group of
      implant-based contralateral management received the highest score for symmetry (p
      ? 0.001), shape (p ? 0.001) and aesthetic result overall (p ? 0.001).
      CONCLUSIONS: This study was the first to use BREAST-Q to analyse the stability of
      breast symmetry following breast reconstruction with long-term results. The
      implant-based contralateral management was the most effective procedure for
      achieving a stable and lasting result to obtain the high satisfaction of
      patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 29359235
TI  - A DNA-scaffold platform enhances a multi-enzymatic cycling reaction.
AB  - OBJECTIVE: We explored the co-localization of multiple enzymes on a DNA backbone
      via a DNA-binding protein, Gene-A* (A*-tag) to increase the efficiency of cascade
      enzymatic reactions. RESULTS: Firefly luciferase (FLuc) and pyruvate
      orthophosphate dikinase (PPDK) were genetically fused with A*-tag and modified
      with single-stranded (ss) DNA via A*-tag. The components were assembled on ssDNA
      by hybridization, thereby enhancing the efficiency of the cascading
      bioluminescent reaction producing light emission from pyrophosphate. The activity
      of A*-tag in each enzyme was investigated with dye-labeled DNA. Co-localization
      of the enzymes via hybridization was examined using a gel shift assay. The multi
      enzyme complex showed significant improvement in the overall efficiency of the
      cascading reaction in comparison to a mixture of free enzymes. CONCLUSION: A*-tag
      is highly convenient for ssDNA modification of versatile enzymes, and it can be
      used for construction of functional DNA-enzyme complexes.

PMID- 29359236
TI  - Role of Plastics on Human Health.
AB  - Plastics, currently the universal workhorse materials of modern economy, because
      of their low cost and varied functional properties are posing serious threat to
      environment and consumer's health in many direct and indirect ways. Rising
      concern about the impact of plastics on environment and human health, has forced
      the industry to look for alternatives. This review studies current understanding
      of benefits and concerns surrounding use of plastics, reviews literature about
      health effects in humans and discusses the current state of evidence, as well as
      future research trends. There is increasing concern regarding additives in
      plastics to which most people are exposed, such as phthalates, bisphenol A or
      polybrominated diphenyl ethers (PBDE), and their detection in humans, leading to
      harmful impact on health. The studies are divided, among many other issues on the
      fact of considering these additives as carcinogens or toxicants, but there is a
      consensus that these chemicals have the ability to alter the endocrine system.
      Human data are limited compared to large body of experimental evidence
      documenting reproductive or developmental toxicity in relation to these compounds
      in animals. The concentrations of these additives in young children, a segment
      particularly sensitive to exogenous insults, are typically higher, indicating the
      need to decrease exposure to these compounds. The rapid increase in usage of
      plastics and increased awareness about its health hazard has lent urgency to the
      whole issue.

PMID- 29359237
TI  - Furthering Precision in Sentinel Node Navigational Surgery for Oral Cancer: a
      Novel Triple Targeting System.
AB  - To describe an innovative sentinel lymph node (SLN) guidance approach using a
      radionuclide tracer, 3D augmented reality-guided imaging, and near infrared (NIR)
      fluorescence over-lay imaging with hand-held probes to optimize accuracy,
      efficiency, and precise navigation for sentinel node (SN) localization in head
      and neck cancer. In a cT1N0M0 squamous cell carcinoma of the tongue, pre
      operative radionuclide lymphoscintigraphy was performed with a sentinel node
      specific radiolabeled tracer. Intraoperatively, a 3D hand-held augmented reality
      (AR) scanning SPECT probe assessed concordance of the SN with pre-operative SPECT
      CT images. The real-time optical video was linked to the SPECT-CT images for
      added precision. Final guidance to the SN was performed using ICG fluorescence
      imaging. Dynamic and SPECT-CT showed bilateral lymphatic drainage from the tumor.
      The 3D hand-held AR SPECT probe SN localization was concordant with pre-operative
      imaging. The optical video successfully demonstrated the lymphatic drainage in
      real-time through a unique overlay fluorescence image. The ICG localized to the
      same nodes identified by both the SPECT-CT and hand-held SPECT images. The use of
      dual radiation and fluorescence tracers improved SN detection, especially for SN
      close to the injection site. The hand-held probes allowed the surgeon to dissect
      continuously, without needing to change tools. The combination of augmented
      reality, nuclear medicine, and over-lay fluorescence imaging allowed greater
      accuracy for matching the preoperative imaging with intraoperative identification
      and precisely guiding the dissection. This method uniquely permitted the surgeon
      to efficiently dissect the SN with accurate visualization and optimal precision.

PMID- 29359238
TI  - Prognostic factors of ALK-negative anaplastic large-cell lymphoma: a single
      institution experience.

PMID- 29359239
TI  - The orally available multikinase inhibitor regorafenib (BAY 73-4506) in multiple
      myeloma.
AB  - A promising approach to the treatment of multiple myeloma (MM) involves agents
      that target not only the myeloma cells directly, but also the tumor
      microenvironment which promotes tumor cell growth, angiogenesis, and MM bone
      disease. Here we investigate the orally available multikinase inhibitor,
      regorafenib (BAY 73-4506), for its therapeutic efficacy in MM. Regorafenib is a
      potent inhibitor of angiogenic (VEGFR 1-3, PDGFR-b) as well as oncogenic (c-KIT,
      RET, FGFR, Raf) kinases. We show that regorafenib induces apoptosis in all MM
      cell lines at below clinically achievable concentrations. Regorafenib overcomes
      the growth advantage conferred by a stroma cell MM and an endothelial cell MM, co
      culture systems, and abrogates growth factor-stimulated MEK, ERK, and AKT
      phosphorylation at nanomolar to micromolar concentrations. Moreover, it inhibits
      endothelial cell growth and tubule formation, abrogates both VEGF secretion and
      VEGF-induced MM cell migration, inhibits osteoclastogenesis, and shows
      synergistic cytotoxicity with dexamethasone, the immunomodulatory drug
      pomalidomide, and the p110delta inhibitor idelalisib. Most importantly,
      regorafenib significantly delays tumor growth in a xenograft mouse model of human
      MM. These results provide the rationale for further clinical evaluation of
      regorafenib, alone and in combination, in the treatment of MM.

PMID- 29359241
TI  - Utility of Retrievable Inferior Vena Cava Filters: A Systematic Literature Review
      and Analysis of the Reasons for Nonretrieval of Filters with Temporary
      Indications.
AB  - OBJECTIVE: To investigate the use of retrievable inferior vena cava (IVC) filters
      in the current practice and analyze the causes of filter left in situ despite
      initial plans for retrieval. METHODS: A systematic search of all English-language
      studies of retrievable IVC filters was conducted, including clinical trials and
      observational studies published between January 1984 and March 2016. RESULTS: A
      total of 103 studies were identified, including 10 filter models in 20,319
      patients. Placement indications were reported for 11,128 (54.8%) patients,
      including therapeutic (n = 6270; 56.3%) and prophylactic (n = 4858; 43.7%)
      indications. A total of 13,224 (65.1%) filters were left as permanent devices;
      7095 (34.9%) filters were removed. The reasons for filter nonretrieval among the
      5308 (40.1%) reported cases were primary permanent indication (21.2%; 1127/5308),
      death (19.4%; 1031/5308), ongoing pulmonary embolism (PE) protection (19.0%;
      1011/5308), failed retrieval (13.7%; 725/5308), loss to follow-up (13.0%;
      689/5308), discontinued care (4.4%; 235/5308), physician oversight (4.0%;
      213/5308), patient morbidity (2.8%; 149/5308), and patient refusal (2.4%;
      128/5308). A total of 7820 patients presented for filter retrieval, and 7095
      filters (90.7%) were successfully removed, with a mean indwelling time of 106.6
      +/- 47.3 days. Breakthrough PE was reported in 2.1% (191/9169) of patients.
      Filter tilt, recurrent deep vein thrombosis, penetration, IVC thrombosis,
      migration, and fracture occurred in 7.7% (798/10,348), 7.1% (362/5092), 5.4%
      (379/7001), 3.9% (345/8788), 1.4% (160/11,679), and 0.5% (50/9509) of patients,
      respectively. CONCLUSIONS: Approximately two-thirds of retrievable filters were
      not retrieved even though more than 85% of the filters were initially intended
      for temporary use. The major reasons for filter left in situ despite initial
      plans for retrieval were death, need for ongoing PE protection, failed retrieval,
      loss to follow-up, discontinued care, and physician oversight.

PMID- 29359240
TI  - Feasibility of Percutaneous Intrahepatic Split by Microwave Ablation (PISA) After
      Portal Vein Embolization for Hypertrophy of Future Liver Remnant: The
      Radiological Stage-1 ALPPS.
AB  - PURPOSE: To assess the feasibility of radiological stage-1 ALPPS, associating
      liver partition and portal vein ligation for staged hepatectomy, by combining
      portal vein embolization (PVE) with percutaneous intrahepatic split by ablation
      (PISA). MATERIALS AND METHODS: Three patients (mean age 65.0 +/- 7.3 years)
      underwent PVE and PISA. PISA was performed 21 days after PVE by microwave
      ablation to create a continuous intrahepatic cutting plane. Abdominal CT
      examinations were performed before and after PVE and PISA. The future liver
      remnant (FLR) volume was calculated by semiautomatic segmentation, and increase
      was reported as a percentage of the pre-procedural volume. The FLR/body weight
      (FLR/BW) ratio was calculated; a ratio greater than 0.8% was considered
      sufficient for guaranteeing adequate liver function after surgery. The liver
      function before and after PISA was also evaluated by 99mTc-mebrofenin
      hepatobiliary scintigraphy. Patients' laboratory tests, performance status,
      ability to walk were assessed before and after PVE and PISA procedures. RESULTS:
      No procedure-related complications were recorded. The FLR volume increase in each
      patient was 42.0, 33.1 and 30.4% within 21 days of PVE and 109.3, 68.1 and 71.7%
      within 10 days after PISA. The FLR/BW ratios were 0.76, 0.66, 0.63% and 1.13,
      0.83, 0.83% after PVE and PISA procedures, respectively. Two patients underwent
      successful right hepatectomy; in one patient, despite 1.13% FLR/BW, surgery was
      not performed because of the absolute rejection of blood transfusion due to the
      patient's religious convictions. CONCLUSION: Radiological stage-1 ALPPS is a
      feasible, minimally invasive option to be further investigated to become an
      effective alternative to surgical stage-1 ALPPS.

PMID- 29359242
TI  - Generating Multivariate Ordinal Data via Entropy Principles.
AB  - When conducting robustness research where the focus of attention is on the impact
      of non-normality, the marginal skewness and kurtosis are often used to set the
      degree of non-normality. Monte Carlo methods are commonly applied to conduct this
      type of research by simulating data from distributions with skewness and kurtosis
      constrained to pre-specified values. Although several procedures have been
      proposed to simulate data from distributions with these constraints, no
      corresponding procedures have been applied for discrete distributions. In this
      paper, we present two procedures based on the principles of maximum entropy and
      minimum cross-entropy to estimate the multivariate observed ordinal distributions
      with constraints on skewness and kurtosis. For these procedures, the correlation
      matrix of the observed variables is not specified but depends on the
      relationships between the latent response variables. With the estimated
      distributions, researchers can study robustness not only focusing on the levels
      of non-normality but also on the variations in the distribution shapes. A
      simulation study demonstrates that these procedures yield excellent agreement
      between specified parameters and those of estimated distributions. A robustness
      study concerning the effect of distribution shape in the context of confirmatory
      factor analysis shows that shape can affect the robust [Formula: see text] and
      robust fit indices, especially when the sample size is small, the data are
      severely non-normal, and the fitted model is complex.

PMID- 29359243
TI  - Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and
      high lactate: expanding the phenotype of ISCA2 gene mutations.
AB  - A homoallelic missense founder mutation of the iron-sulfur cluster assembly 2
      (ISCA2) gene has been recently reported in six cases affected by an autosomal
      recessive infantile neurodegenerative mitochondrial disorder. We documented a
      case of a 2-month-old girl presenting with severe hypotonia and nystagmus, who
      rapidly deteriorated and died at the age of three months. Increased cerebral
      spinal fluid level of lactate, documented also at the brain spectroscopy,
      involvement of the cortex, restricted diffusion of white and gray matter
      abnormalities, sparing of the corpus callosum and extensive involvement of the
      spinal cord were observed. Her clinical presenting features and course as well as
      some neuroradiological findings mimicked those of early-onset leukoencephalopathy
      with brainstem and spinal cord involvement and high brain lactate (LBSL). The
      analysis of the mitochondrial respiratory chain function showed a reduced
      activity of complexes II and IV. The girl harboured two heterozygous mutations in
      the ISCA2 gene. A comprehensive review of the literature and a comparison with
      the cases of early onset LBSL enabled us to highlight significant differences in
      the clinical, biochemical and neuroradiological phenotype between the two
      conditions, which also emerged from the comparison with the other 6 reported
      cases of ISCA2 gene mutation previously reported. In summary, this represents the
      second report ever published associating ISCA2 gene mutation with a mitochondrial
      leukoencephalopathy, with a different genetic mechanism to the previous cases.
      Molecular analysis of ISCA2 should be included in the genetic panel for the
      diagnosis of early onset mitochondrial leukoencephalopathies.

PMID- 29359244
TI  - A scoring model for predicting advanced colorectal neoplasia in a screened
      population of asymptomatic Japanese individuals.
AB  - BACKGROUND: Risk stratification of screened populations could help improve
      colorectal cancer (CRC) screening. Use of the modified Asia-Pacific Colorectal
      Screening (APCS) score has been proposed in the Asia-Pacific region. This study
      was performed to build a new useful scoring model for CRC screening. METHODS:
      Data were reviewed from 5218 asymptomatic Japanese individuals who underwent
      their first screening colonoscopy. Multivariate logistic regression was used to
      investigate risk factors for advanced colorectal neoplasia (ACN), and a new
      scoring model for the prediction of ACN was developed based on the results. The
      discriminatory capability of the new model and the modified APCS score were
      assessed and compared. Internal validation was also performed. RESULTS: ACN was
      detected in 225 participants. An 8-point scoring model for the prediction of ACN
      was developed using five independent risk factors for ACN (male sex, higher age,
      presence of two or more first-degree relatives with CRC, body mass index of >
      22.5 kg/m2, and smoking history of > 18.5 pack-years). The prevalence of ACN was
      1.6% (34/2172), 5.3% (127/2419), and 10.2% (64/627) in participants with scores
      of < 3, >= 3 to < 5, and >= 5, respectively. The c-statistic of the scoring model
      was 0.70 (95% confidence interval, 0.67-0.73) in both the development and
      internal validation sets, and this value was higher than that of the modified
      APCS score [0.68 (95% confidence interval, 0.65-0.71), P = 0.03]. CONCLUSIONS: We
      built a new simple scoring model for prediction of ACN in a Japanese population
      that could stratify the screened population into low-, moderate-, and high-risk
      groups.

PMID- 29359245
TI  - Cardiovascular delivery of drugs and biotherapeutics.

PMID- 29359246
TI  - Development of sustained-release microparticles containing tamsulosin HCl for
      orally disintegrating tablet using melt-adsorption method.
AB  - In this study, using the melt-adsorption method, we developed sustained-release
      microparticles containing the potent drug, tamsulosin HCl, for use as orally
      disintegrating tablets. A high-speed kneading granulator was used, enabling
      temperature modulation and uniform material distribution. A lipid and
      ethylcellulose suspension (Surelease(r)) was applied to retard drug release, and
      magnesium aluminometasilicate (Neusilin(r)) was used as adsorbent. Among various
      lipid candidates for melt-adsorption, beeswax and glyceryl behenate were selected
      due to their high mechanical strength. Hot stage microscopy and powder X-ray
      diffraction analysis results showed compatibility between tamsulosin HCl and both
      lipids. Characteristic adsorption behavior was observed depending on the
      physicochemical properties of each composition. Especially, the specific surface
      area of Neusilin(r) decreased with increasing amounts of Surelease(r), attributed
      to the pore-covering effect of Surelease(r), which significantly increased the
      size of the microparticles after the lipid adsorption. For a Surelease(r)-to
      beeswax ratio 1:50, both the desired particle size distribution and low burst
      release were achieved. Furthermore, the orally disintegrating tablet containing
      optimized microparticles had acceptable tablet hardness and rapid disintegration.
      Herein, the feasibility of melt-adsorption for the preparation of sustained
      release microparticles was well demonstrated. With its convenience and
      efficiency, the proposed method is a promising alternative to conventional
      methods, which are relatively difficult and time consuming.

PMID- 29359247
TI  - Neonicotinoids thiamethoxam and clothianidin adversely affect the colonisation of
      invertebrate populations in aquatic microcosms.
AB  - Surface waters are sometimes contaminated with neonicotinoids: a widespread,
      persistent, systemic class of insecticide with leaching potential. Previous
      ecotoxicological investigations of this chemical class in aquatic ecosystems have
      largely focused on the impacts of the neonicotinoid imidacloprid; few empirical,
      manipulative studies have investigated the effect on invertebrate abundances of
      two other neonicotinoids which are now more widely used: clothianidin and
      thiamethoxam. In this study, we employ a simple microcosm semi-field design,
      incorporating a one-off contamination event, to investigate the effect of these
      pesticides at field-realistic levels (ranging from 0 to 15 ppb) on invertebrate
      colonisation and survival in small ephemeral ponds. In line with previous
      research on neonicotinoid impacts on aquatic invertebrates, significant negative
      effects of both neonicotinoids were found. There were clear differences between
      the two chemicals, with thiamethoxam generally producing stronger negative
      effects than clothianidin. Populations of Chironomids (Diptera) and Ostracoda
      were negatively affected by both chemicals, while Culicidae appeared to be
      unaffected by clothianidin at the doses used. Our data demonstrate that field
      realistic concentrations of neonicotinoids are likely to reduce populations of
      invertebrates found in ephemeral ponds, which may have knock on effects up the
      food chain. We highlight the importance of developing pesticide monitoring
      schemes for European surface waters.

PMID- 29359249
TI  - Phytoremediation of a petroleum-polluted soil by native plant species in Lorestan
      Province, Iran.
AB  - Petroleum hydrocarbons are potentially toxic for organisms due to the inherent
      properties, such as solubility, volatility, and biodegradability. The petroleum
      materials released from corroded old pipelines would pollute soils, shallow
      groundwater and air as a consequence, and threat the health of human and
      environment. Therefore, the removal of these compounds from environment is vital.
      The stability of these pollutants at the soil and their gradual accumulation over
      time would disrupt the normal function of the soil, such as reduced agricultural
      capability. In this research, the influence of two plant species (Bromus tectorum
      L. and Festuca arundinacea) with different amendments including arbuscular
      mycorrhizal fungi, alfalfa residues, and nutrient solution on the degradation
      rate of petroleum hydrocarbons in soil was studied. The results showed that the
      most effective treatment for petroleum remediation was related to B. tectorum L.
      plant when treated with mycorrhizal fungi and nutrient solution. The degradation
      rate during 40 days was about 83.27% when compared to the control. Arbuscular
      mycorrhizal associations are important in the restoration of degraded ecosystems
      because of the benefits to their symbiotic partners. This fungal
      phytotechnological mechanism is still in its infancy and there has been little
      research on aged-contaminated soils.

PMID- 29359248
TI  - Water treatment by new-generation graphene materials: hope for bright future.
AB  - Water is the most important and essential component of earth's ecosystem playing
      a vital role in the proper functioning of flora and fauna. But, our water
      resources are contaminating continuously. The whole world may be in great water
      scarcity after few decades. Graphene, a single-atom thick carbon nanosheet, and
      graphene nanomaterials have bright future in water treatment technologies due to
      their extraordinary properties. Only few papers describe the use of these
      materials in water treatment by adsorption, filtration, and photodegradation
      methods. This article presents a critical evaluation of the contribution of
      graphene nanomaterials in water treatment. Attempts have been made to discuss the
      future perspectives of these materials in water treatment. Besides, the efforts
      are made to discuss the nanotoxicity and hazards of graphene-based materials. The
      suggestions are given to explore the full potential of these materials along with
      precautions of nanotoxicity and its hazards. It was concluded that the future of
      graphene-based materials is quite bright.

PMID- 29359250
TI  - Multi-perspective comparisons and mitigation implications of SO2 and NO x
      discharges from the industrial sector of China: a decomposition analysis.
AB  - This study is the first attempt to investigate the drivers of Chinese industrial
      SO2 and NO x emissions from both periodic and structural perspectives through a
      decomposition analysis using the logarithmic mean Divisia index (LMDI). The two
      pollutants' emissions were decomposed into output effects, structural effects,
      clean production effects, and pollution abatement effects. The results showed
      that China's industrial SO2 discharge increased by 1.14 Mt during 2003-2014, and
      the contributions from the four effects were 23.17, - 1.88, - 3.80, and - 16.36
      Mt, respectively. Likewise, NO x discharge changed by - 3.44 Mt over 2011-2014,
      and the corresponding contributions from the four effects were 2.97, - 0.62, -
      1.84, and - 3.95 Mt. Thus, the output effect was mainly responsible for the
      growth of the two discharges. The average annual contribution rates of SO2 and NO
      x from output were 14.33 and 5.97%, respectively, but pollution abatement
      technology presented the most obvious mitigating effects (- 10.11 and - 7.92%),
      followed by the mitigating effects of clean production technology (- 2.35 and -
      3.7%), and the mitigation from the structural effect was the weakest (- 1.16 and 
      1.25%, respectively), which meant pollutant reduction policies related to
      industrial structure adjustment should be a long-term measure for the two
      discharges. In addition, the sub-sectors of I20 (manufacture of raw chemical
      materials and chemical products), I24 (manufacture of non-metallic mineral
      products), and I26 (smelting and pressing of non-ferrous metals) were the major
      contributors to both discharges. Thus, these sub-sectors should be given priority
      consideration when designing mitigation-related measures. Last, some particular
      policy implications were recommended for reducing the two discharges, including
      that the government should seek a technological discharge reduction route.

PMID- 29359251
TI  - Can Vaccination Save a Zika Virus Epidemic?
AB  - Zika virus (ZIKV) is a vector-borne disease that has rapidly spread during the
      year 2016 in more than 50 countries around the world. If a woman is infected
      during pregnancy, the virus can cause severe birth defects and brain damage in
      their babies. The virus can be transmitted through the bites of infected
      mosquitoes as well as through direct contact from human to human (e.g., sexual
      contact and blood transfusions). As an intervention for controlling the spread of
      the disease, we study a vaccination model for preventing Zika infections.
      Although there is no formal vaccine for ZIKV, The National Institute of Allergy
      and Infectious Diseases (part of the National Institutes of Health) has launched
      a vaccine trial at the beginning of August 2016 to control ZIKV transmission,
      patients who received the vaccine are expected to return within 44 weeks to
      determine if the vaccine is safe. Since it is important to understand ZIKV
      dynamics under vaccination, we formulate a vaccination model for ZIKV spread that
      includes mosquito as well as sexual transmission. We calculate the basic
      reproduction number of the model to analyze the impact of relatively, perfect and
      imperfect vaccination rates. We illustrate several numerical examples of the
      vaccination model proposed as well as the impact of the basic reproduction
      numbers of vector and sexual transmission and the effect of vaccination effort on
      ZIKV spread. Results show that high levels of sexual transmission create larger
      cases of infection associated with the peak of infected humans arising in a
      shorter period of time, even when a vaccine is available in the population.
      However, a high level of transmission of Zika from vectors to humans compared
      with sexual transmission represents that ZIKV will take longer to invade the
      population providing a window of opportunities to control its spread, for
      instance, through vaccination.

PMID- 29359252
TI  - Smartphone-based objective monitoring in bipolar disorder: status and
      considerations.
AB  - In 2001, the WHO stated that: "The use of mobile and wireless technologies to
      support the achievement of health objectives (mHealth) has the potential to
      transform the face of health service delivery across the globe". Within mental
      health, interventions and monitoring systems for depression, anxiety, substance
      abuse, eating disorder, schizophrenia and bipolar disorder have been developed
      and used. The present paper presents the status and findings from studies using
      automatically generated objective smartphone data in the monitoring of bipolar
      disorder, and addresses considerations on the current literature and
      methodological as well as clinical aspects to consider in the future studies.

PMID- 29359253
TI  - Does co-inoculation of Lactuca serriola with endophytic and arbuscular
      mycorrhizal fungi improve plant growth in a polluted environment?
AB  - Phytoremediation of polluted sites can be improved by co-inoculation with
      mycorrhizal and endophytic fungi. In this study, the effects of single- and co
      inoculation of Lactuca serriola with an arbuscular mycorrhizal (AM) fungus,
      Rhizoglomus intraradices, and endophytic fungi, Mucor sp. or Trichoderma
      asperellum, on plant growth, vitality, toxic metal accumulation, sesquiterpene
      lactone production and flavonoid concentration in the presence of toxic metals
      were evaluated. Inoculation with the AM fungus increased biomass yield of the
      plants grown on non-polluted and polluted substrate. Co-inoculation with the AM
      fungus and Mucor sp. resulted in increased biomass yield of plants cultivated on
      the polluted substrate, whereas co-inoculation with T. asperellum and the AM
      fungus increased plant biomass on the non-polluted substrate. In the presence of
      Mucor sp., mycorrhizal colonization and arbuscule richness were increased in the
      non-polluted substrate. Co-inoculation with the AM fungus and Mucor sp. increased
      Zn concentration in leaves and roots. The concentration of sesquiterpene lactones
      in plant leaves was decreased by AM fungus inoculation in both substrates.
      Despite enhanced host plant costs caused by maintaining symbiosis with numerous
      microorganisms, interaction of wild lettuce with both mycorrhizal and endophytic
      fungi was more beneficial than that with a single fungus. The study shows the
      potential of double inoculation in unfavourable environments, including
      agricultural areas and toxic metal-polluted areas.

PMID- 29359254
TI  - Qualitative assessment of awake nasopharyngoscopy for prediction of oral
      appliance treatment response in obstructive sleep apnoea.
AB  - PURPOSE: Clinical methods to identify responders to oral appliance (OA) therapy
      for obstructive sleep apnoea (OSA) are needed. Awake nasopharyngoscopy during
      mandibular advancement, with image capture and subsequent processing and
      analysis, may predict treatment response. A qualitative assessment of awake
      nasopharyngoscopy would be simpler for clinical practice. We aimed to determine
      if a qualitative classification system of nasopharyngoscopic observations
      reflects treatment response. METHODS: OSA patients were recruited for treatment
      with a customised two-piece OA. A custom scoring sheet was used to record
      observations of the pharyngeal airway (velopharynx, oropharynx, hypopharynx)
      during supine nasopharyngoscopy in response to mandibular advancement and
      performance of the Muller manoeuvre. Qualitative scores for degree (< 25%, 25
      50%, 50-75%, > 75%), collapse pattern (concentric, anteroposterior, lateral) and
      diameter change (uniform, anteroposterior, lateral) were recorded. Treatment
      outcome was confirmed by polysomnography after a titration period of 14.6 +/- 9.8
      weeks. Treatment response was defined as (1) Treatment AHI < 5, (2) Treatment AHI
      < 10 plus > 50% AHI reduction and (3) > 50% AHI reduction. RESULTS: Eighty OSA
      patients (53.8% male) underwent nasopharyngoscopy. The most common
      naspharyngoscopic observation with mandibular advancement was a small (< 50%)
      increase in velopharyngeal lateral diameter (37.5%). The majority of subjects
      (72.5%) were recorded as having > 75% velopharyngeal collapse on performance of
      the Muller manoeuvre. Mandibular advancement reduced the observed level of
      pharyngeal collapse at all three pharyngeal regions (p < 0.001). None of the
      nasopharyngoscopic qualitative scores differed between responder and non
      responder groups. CONCLUSION: Qualitative assessment of awake nasopharyngoscopy
      appears useful for assessing the effect of mandibular advancement on upper airway
      collapsibility. However, it is not sensitive enough to predict oral appliance
      treatment outcome.

PMID- 29359255
TI  - Fabrication of a New Self-assembly Compound of CsTi2NbO7 with Cationic Cobalt
      Porphyrin Utilized as an Ascorbic Acid Sensor.
AB  - A novel sandwich-structured nanocomposite based on Ti2NbO7- nanosheets and cobalt
      porphyrin (CoTMPyP) was fabricated through electrostatic interaction, in which
      CoTMPyP has been successfully inserted into the lamellar spacing of layered
      titanoniobate. The resultant Ti2NbO7/CoTMPyP nanocomposite was characterized by
      XRD, SEM, TEM, EDS, FT-IR, and UV-vis. It is demonstrated that the intercalated
      CoTMPyP molecules were found to be tilted approximately 63 degrees  against
      Ti2NbO7- layers. The glass carbon electrode (GCE) modified by Ti2NbO7/CoTMPyP
      film showed a fine diffusion-controlled electrochemical redox process.
      Furthermore, the Ti2NbO7/CoTMPyP-modified electrode exhibited excellent
      electrocatalytic oxidation activity of ascorbic acid (AA). Differential pulse
      voltammetric studies demonstrated that the intercalated nanocomposite detects AA
      linearly over a concentration range of 4.99 * 10-5 to 9.95 * 10-4 mol L-1 with a
      detection limit of 3.1 * 10-5 mol L-1 at a signal-to-noise ratio of 3.0.

PMID- 29359256
TI  - Tibial tubercle osteotomy (TTO) in total knee arthroplasty, is it worth it? A
      review of the literature.
AB  - INTRODUCTION: Tibial tubercle osteotomy (TTO) is a well-established extensile
      approach to improve joint visualization and implant removal. Despite this, TTO is
      a challenging technique with a long learning curve and potential pitfalls.
      Complications are not infrequent, even if performing the correct surgical steps.
      Aim of this paper is to review the current literature about TTO, its safeness and
      reliability, and finally the complications rate. MATERIALS AND METHODS: We
      performed a systematic review of the available English literature, considering
      the outcomes and the complications of TTO. The combinations of keyword were
      "tibial tubercle osteotomy", "total knee arthroplasty", "total knee revision",
      "outcomes", "complication" and "surgical approach". RESULTS: From the starting
      322 papers available, 26 manuscripts were finally included. Most of the papers
      show significant improvements in clinical outcomes, both in primary and in
      revision procedures. Radiographic fragment healing is close to 100%. Related
      complications can range from 3.8-20%. CONCLUSION: TTO may be necessary to correct
      pathological tuberosity position or patella tracking. However, TTO is a
      challenging technique to improve the surgical approach during total knee
      arthroplasty. A strict surgical technique can lead to better results and to
      minimize complications. However, it is not clear if the improved outcome can
      outweigh the longer surgery and the higher risk of pitfalls.

PMID- 29359257
TI  - Speedup computation of HD-sEMG signals using a motor unit-specific electrical
      source model.
AB  - Nowadays, bio-reliable modeling of muscle contraction is becoming more accurate
      and complex. This increasing complexity induces a significant increase in
      computation time which prevents the possibility of using this model in certain
      applications and studies. Accordingly, the aim of this work is to significantly
      reduce the computation time of high-density surface electromyogram (HD-sEMG)
      generation. This will be done through a new model of motor unit (MU)-specific
      electrical source based on the fibers composing the MU. In order to assess the
      efficiency of this approach, we computed the normalized root mean square error
      (NRMSE) between several simulations on single generated MU action potential
      (MUAP) using the usual fiber electrical sources and the MU-specific electrical
      source. This NRMSE was computed for five different simulation sets wherein
      hundreds of MUAPs are generated and summed into HD-sEMG signals. The obtained
      results display less than 2% error on the generated signals compared to the same
      signals generated with fiber electrical sources. Moreover, the computation time
      of the HD-sEMG signal generation model is reduced to about 90% compared to the
      fiber electrical source model. Using this model with MU electrical sources, we
      can simulate HD-sEMG signals of a physiological muscle (hundreds of MU) in less
      than an hour on a classical workstation. Graphical Abstract Overview of the
      simulation of HD-sEMG signals using the fiber scale and the MU scale. Upscaling
      the electrical source to the MU scale reduces the computation time by 90%
      inducing only small deviation of the same simulated HD-sEMG signals.

PMID- 29359258
TI  - A Technique for Thermal Desorption Analyses Suitable for Thermally-Labile,
      Volatile Compounds.
AB  - Many plant and insect interactions are governed by odors released by the plants
      or insects and there exists a continual need for new or improved methods to
      collect and identify these odors. Our group has for some time studied below
      ground, plant-produced volatile signals affecting nematode and insect behavior.
      The research requires repeated sampling of volatiles of intact plant/soil systems
      in the laboratory as well as the field with the help of probes to minimize
      unwanted effects on the systems we are studying. After evaluating solid adsorbent
      filters with solvent extraction or solid phase micro extraction fiber sample
      collection, we found dynamic sampling of small air volumes on Tenax TA filters
      followed by thermal desorption sample introduction to be the most suitable
      analytical technique for our applications. Here we present the development and
      evaluation of a low-cost and relatively simple thermal desorption technique where
      a cold trap cooled with liquid carbon dioxide is added as an integral part of a
      splitless injector. Temperature gradient-based focusing and low thermal mass
      minimizes aerosol formation and eliminates the need for flash heating, resulting
      in low sample degradation comparable to solvent-based on-column injections.
      Additionally, since the presence of the cold trap does not affect normal
      splitless injections, on-the-fly switching between splitless and thermal
      desorption modes can be used for external standard quantification.

PMID- 29359259
TI  - Extra-articular distal tibia fractures-controversies regarding treatment options.
      A single-centre prospective comparative study.
AB  - Distal tibia fractures are reported to have a high complication rate pre
      operatively as well as post-operatively, which can include open fractures, soft
      tissue damage, infection, malalignment, pseudarthrosis and ankle arthrosis. The
      operative treatment for the extra-articular distal tibia fractures is a
      controversial topic in the orthopaedic literature. Some of these fractures are
      proximal enough to be treated with an intramedullary nail while others are too
      distal for that. The aim of our study was to compare the results we have had with
      intramedullary nail (IMN) and minimally invasive plate osteosynthesis (MIPO) in
      distal metaphyseal (extra-articular) tibia fractures. The study was designed
      prospectively between January 2013 and March 2016 and took place on the
      Orthopaedics and Traumatology ward of a Clinical Emergency County Hospital in
      western Romania. The follow-up visits were scheduled one month, three months and
      six months post-operatively. For evaluating the ankle function, we used the
      Olerud-Molander ankle score (OMAS) and union was evaluated at six months on ankle
      X-rays. At the six-month follow-up visit the average scores were 75.55 (20-100)
      for the IMN lot and 74.23 (20-90) for the MIPO lot, without finding any
      statistical difference between the two groups (p >0.1). At the six-month follow
      up, X-ray union was objected in 48 (90.5%) of our patients, the IMN lot having
      worse results (85.18%) than the MIPO lot (96.15%). The results we encountered
      showed little to no statistical difference when it comes to the functional score
      we used (OMAS score), leading us to believe that you can achieve comparable
      results with both implants.

PMID- 29359262
TI  - Numerical Investigation of the Effect of Additional Pulmonary Blood Flow on
      Patient-Specific Bilateral Bidirectional Glenn Hemodynamics.
AB  - The effect of additional pulmonary blood flow (APBF) on the hemodynamics of
      bilateral bidirectional Glenn (BBDG) connection was marginally discussed in
      previous studies. This study assessed this effect using patient-specific
      numerical simulation. A 15-year-old female patient who underwent BBDG was
      enrolled in this study. Patient-specific anatomy, flow waveforms, and pressure
      tracings were obtained using computed tomography, Doppler ultrasound technology,
      and catheterization, respectively. Computational fluid dynamic simulations were
      performed to assess flow field and derived hemodynamic metrics of the BBDG
      connection with various APBF. APBF showed noticeable effects on the hemodynamics
      of the BBDG connection. It suppressed flow mixing in the connection, which
      resulted in a more antegrade flow structure. Also, as the APBF rate increases,
      both power loss and reflux in superior venae cavae (SVCs) monotonically increases
      while the flow ratio of the right to the left pulmonary artery (RPA/LPA)
      monotonically decreases. However, a non-monotonic relationship was observed
      between the APBF rate and indexed power loss. A high APBF rate may result in a
      good flow ratio of RPA/LPA but with the side effect of bad power loss and
      remarkable reflux in SVCs, and vice versa. A moderate APBF rate could be
      favourable because it leads to an optimal indexed power loss and achieves the
      acceptable flow ratio of RPA/LPA without causing severe power loss and reflux in
      SVCs. These findings suggest that patient-specific numerical simulation should be
      used to assist clinicians in determining an appropriate APBF rate based on
      desired outcomes on a patient-specific basis.

PMID- 29359261
TI  - Transplantation in patients with iron overload: is there a place for magnetic
      resonance imaging? : Transplantation in iron overload.
AB  - In iron overload diseases (thalassemia, sickle cell, and myelodysplastic
      syndrome), iron is deposited in all internal organs, leading to functional
      abnormalities. Hematopoietic stem cell transplantation (HSCT) is the only
      treatment offering a potential cure in these diseases. Our aim was to describe
      the experience in the field and the role of magnetic resonance imaging in the
      evaluation of iron overload before and after HSCT. Magnetic resonance imaging
      (MRI), using T2*, is the most commonly used tool to diagnose myocardial-liver
      iron overload and guide tailored treatment. Currently, HSCT offers complete cure
      in thalassemia major, after overcoming the immunologic barrier, and should be
      considered for all patients who have a suitable donor. The overall thalassemia
      free survival of low-risk, HLA-matched sibling stem cell transplantation patients
      is 85-90%, with a 95% overall survival. The problems of rejection and engraftment
      are improving with the use of adequate immunosuppression. However, a detailed
      iron assessment of both heart and liver is necessary for pre- and post-transplant
      evaluation. In iron overload diseases, heart and liver iron evaluation is
      indispensable not only for the patients' survival, but also for evaluation before
      and after HSCT.

PMID- 29359260
TI  - Clinical impact of oral antidiabetic medications in heart failure patients.
AB  - Heart failure (HF) is a common complication in patients with type 2 diabetes and
      it is closely associated with high morbidity and mortality rate. The incidence of
      cardiovascular events in patients with diabetes is related to high levels of
      glycemia, expressed by increase of HbA1c levels. However, there is little
      evidence to indicate that glycemic control can reduce the incidence of HF events
      in this population. Recently, several new antidiabetic drugs have been proposed
      although the exact clinical impact on heart failure occurrence and deterioration
      is under debate. Most common oral antidiabetic medication such as SGLT2, GLP-1
      receptor agonist, metformin, and DPP4 inhibitor revealed peculiar metabolic and
      biomolecular signal effects. Moreover, the negative effects of thiazolidinediones
      on HF prognosis, on cardiac function, and exercise tolerance is of great
      interest. Conversely, several studies on GLP-1RA have highlighted many positive
      effects on cardiac myocytes, reducing apoptosis through cAMP/PKA/CRCB-mediated
      pathways protecting against oxidative stress. DPP-4 inhibitors have a
      controversial effect: saxagliptin and alogliptin may increase the risk of HF as
      opposed to vildagliptin and sitagliptin. Metformin increases myocardial ATP
      levels due to activation of 5-AMPK and this could explain the positive link
      between the drug and events rate reduction in diabetic patients with HF. The more
      interesting class of new drugs is SGLT2 inhibitors, that seems to have a positive
      effect on cardiac function by 38% reduction of HF incidence and mortality with
      empagliflozin treatment. In this review, we would analyze the specific effects of
      each class so as to better elucidate the clinical impact of antidiabetic drug on
      HF for guiding the clinicians in the choice of a best individualized therapy.

PMID- 29359263
TI  - QTL mapping of flag leaf-related traits in wheat (Triticum aestivum L.).
AB  - KEY MESSAGE: QTL controlling flag leaf length, flag leaf width, flag leaf area
      and flag leaf angle were mapped in wheat. This study aimed to advance our
      understanding of the genetic mechanisms underlying morphological traits of the
      flag leaves of wheat (Triticum aestivum L.). A recombinant inbred line (RIL)
      population derived from ND3331 and the Tibetan semi-wild wheat Zang1817 was used
      to identify quantitative trait loci (QTLs) controlling flag leaf length (FLL),
      flag leaf width (FLW), flag leaf area (FLA), and flag leaf angle (FLANG). Using
      an available simple sequence repeat genetic linkage map, 23 putative QTLs for
      FLL, FLW, FLA, and FLANG were detected on chromosomes 1B, 2B, 3A, 3D, 4B, 5A, 6B,
      7B, and 7D. Individual QTL explained 4.3-68.52% of the phenotypic variance in
      different environments. Four QTLs for FLL, two for FLW, four for FLA, and five
      for FLANG were detected in at least two environments. Positive alleles of 17 QTLs
      for flag leaf-related traits originated from ND3331 and 6 originated from
      Zang1817. QTLs with pleiotropic effects or multiple linked QTL were also
      identified on chromosomes 1B, 4B, and 5A; these are potential target regions for
      fine-mapping and marker-assisted selection in wheat breeding programs.

PMID- 29359264
TI  - Characterization of a complex chromosomal rearrangement involving chromosomes 1,
      3, and 4 in a slightly affected male with bad obstetrics history.

PMID- 29359265
TI  - Heterologous expression of Oenococcus oeni sHSP20 confers temperature stress
      tolerance in Escherichia coli.
AB  - Small heat shock proteins (sHSPs) are heat shock proteins sized 12-43 kDa that
      can protect proteins from denaturation, particularly under high temperature;
      sHSPs thus increase the heat tolerance capability of an organisms enabling
      survival in adverse climates. sHSP20 is overexpressed in Oenococcus oeni in
      response to low temperatures. However, we found that overexpression of sHSP20 in
      Escherichia coli BL21 increased the microbial survival ratio at 50  degrees C by
      almost 2 h. Adding sHSP20 to the glutamate dehydrogenase solution significantly
      increased the stability of the enzyme at high temperature (especially at 60-70 
      degrees C), low pH values (especially below 6.0), and high concentration of metal
      ions of Ga2+, Zn2+, Mn2+, and Fe3+. Notably, the coexpression of sHSP20
      significantly enhanced soluble expression of laccase from Phomopsis sp. XP-8
      (CCTCCM209291) in E. coli without codon optimization, as well as the activity and
      heat stability of the expressed enzyme. In addition to the chaperone activity of
      sHSP20 in the gene containing host in vivo and the enzyme heat stability in
      vitro, our study indicated the capability of coexpression of sHSP20 to increase
      the efficiency of prokaryotic expression of fungal genes and the activity of
      expressed enzymes. Graphical abstract ?.

PMID- 29359266
TI  - The place of liver transplantation in the treatment of hepatic metastases from
      neuroendocrine tumors: Pros and cons.
AB  - Liver metastases occur in nearly half of NET patients (MNETs) and heavily affect
      prognosis, with 5-yr. OS around 19-38%. Although it is difficult to show outcome
      differences for available treatments, due to the long course of disease, surgery
      for MNETs remains the most effective option in terms of survival and symptom
      control. Since MNETs frequently present as an oligo-metastatic, liver-limited
      disease, unresectable in 80% of cases, liver transplantation (LT) has emerged as
      a potential curative treatment. Nevertheless, experience with LT for MNETs is
      limited and burdened by highly heterogeneous outcomes and significant recurrence
      rate, mostly explained by the variability of selection criteria. Several
      prognostic factors have been identified: extended surgery on primary tumor
      associated to LT, elderly patients, pancreatic primary (pNET), extensive liver
      involvement, poorly differentiated tumors, high Ki67 levels and short wait time
      to LT. A proper patients' selection based on these data (Milan NET criteria)
      allows a significant survival advantage over non-transplant strategies, with
      excellent outcomes in recent series (69-97.2% 5-yr. OS) as opposed to patients
      undergoing non-surgical treatments (34-50.9%). Evidence indicates LT as the best
      option for selected patients with MNETs. The use of organs for MNETs is therefore
      justified.

PMID- 29359268
TI  - Establishment and proteomic characterization of a novel cell line, NCC-UPS2-C1,
      derived from a patient with undifferentiated pleomorphic sarcoma.
AB  - Undifferentiated pleomorphic sarcoma (UPS) is an aggressive mesenchymal
      malignancy requiring novel therapeutic approaches to improve clinical outcome.
      Patient-derived cancer cell lines are an essential tool for investigating
      molecular mechanisms underlying cancer initiation and development; however, there
      is a lack of patient-derived cell lines of UPS available for research. The
      objective of this study was to develop a patient-derived cell model of UPS. A
      cell line designated NCC-UPS2-C1 was established from the primary tumor tissue of
      an 84-yr-old female patient with UPS. The short tandem repeat pattern of NCC-UPS2
      C1 cells was identical to that of the original tumor and distinct from that of
      any other cell lines deposited in public cell banks. NCC-UPS2-C1 cells were
      maintained as a monolayer culture for over 80 passages during 30 mo and exhibited
      spindle-like morphology, continuous growth, and ability for spheroid formation
      and invasion. Proteomic profiling using mass spectrometry and functional treemap
      analysis revealed that the original tumor and the derived NCC-UPS2-C1 cells had
      similar but distinct protein expression patterns. Our results indicate that a
      novel UPS cell line was successfully established and could be used to study UPS
      development and effects of anti-cancer drugs. However, the revealed difference
      between proteomes of the original tumor and NCC-UPS2-C1 cells should be further
      investigated to determine the appropriate applications of this cell line in UPS
      research.

PMID- 29359267
TI  - The Development of Latent Dimensions of Psychopathology across Early Childhood:
      Stability of Dimensions and Moderators of Change.
AB  - Recent research has described the structure of psychopathology as including one
      general and multiple specific factors, and this structure has been found in
      samples across development. However, little work has examined whether this
      structure is consistent across time, particularly in young children, within the
      same sample. Further, few studies have examined factors that influence the
      magnitude of the stability of latent dimensions of psychopathology. In the
      present study, we examine these issues in a community sample of 545 children
      assessed at ages 3 and 6. In addition, we explored child temperament, parental
      history of psychopathology, and parenting behaviors as potential moderators of
      the longitudinal stability of latent dimensions of psychopathology. We found that
      the same bifactor model structure identified at age 3 provided an adequate fit to
      the data at age 6. Further, our model revealed significant homotypic stability of
      the general, internalizing, and externalizing specific factors. We also found
      evidence of differentiation of psychopathology over time with the general factor
      at age 3 predicting the externalizing factor at age 6. However, we failed to
      identify moderators of the longitudinal associations between psychopathology
      latent factors. Overall, our results bolster support for the bifactor structure
      of psychopathology, particularly in early childhood.

PMID- 29359270
TI  - Is left ventricular systolic index the new kid in the block?

PMID- 29359269
TI  - Function, distribution, and annotation of characterized cellulases, xylanases,
      and chitinases from CAZy.
AB  - The enzymatic deconstruction of structural polysaccharides, which relies on the
      production of specific glycoside hydrolases (GHs), is an essential process across
      environments. Over the past few decades, researchers studying the diversity and
      evolution of these enzymes have isolated and biochemically characterized
      thousands of these proteins. The carbohydrate-active enzymes database (CAZy)
      lists these proteins and provides some metadata. Here, the sequences and metadata
      of characterized sequences derived from GH families associated with the
      deconstruction of cellulose, xylan, and chitin were collected and discussed.
      First, although few polyspecific enzymes are identified, characterized GH
      families are mostly monospecific. Next, the taxonomic distribution of
      characterized GH mirrors the distribution of identified sequences in sequenced
      genomes. This provides a rationale for connecting the identification of GH
      sequences to specific reactions or lineages. Finally, we tested the annotation of
      the characterized GHs using HMM scan and the protein families database (Pfam).
      The vast majority of GHs targeting cellulose, xylan, and chitin can be identified
      using this publicly accessible approach.

PMID- 29359272
TI  - Rescued diagnostic quality by motion correction of dynamic cardiac positron
      emission tomography (PET) perfusion images.

PMID- 29359271
TI  - Molecular imaging of calcific aortic valve disease.
AB  - Calcific aortic valve disease (CAVD) can progress to symptomatic aortic stenosis
      in a subset of patients. The severity of aortic stenosis and the extent of
      valvular calcification can be evaluated readily by echocardiography, CT, and MRI
      using well-established imaging protocols. However, these techniques fail to
      address optimally other important aspects of CAVD, including the propensity for
      disease progression, risk of complications in asymptomatic patients, and the
      effect of therapeutic interventions on valvular biology. These gaps may be
      addressed by molecular imaging targeted at key biological processes such as
      inflammation, remodeling, and calcification that mediate the development and
      progression of CAVD. In this review, recent advances in valvular molecular
      imaging, including 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF)
      PET, and matrix metalloproteinase-targeted SPECT imaging in the preclinical and
      clinical settings are presented and discussed.

PMID- 29359273
TI  - Comparison of two software systems for quantification of myocardial blood flow in
      patients with hypertrophic cardiomyopathy.
AB  - BACKGORUND: Quantification of myocardial blood flow (MBF) by positron emission
      tomography (PET) is important for investigation of angina in hypertrophic
      cardiomyopathy (HCM). Several software programs exist for MBF quantification, but
      they have been mostly evaluated in patients (with normal cardiac geometry),
      referred for evaluation of coronary artery disease (CAD). Software performance
      has not been evaluated in HCM patients who frequently have hyperdynamic LV
      function, LV outflow tract (LVOT) obstruction, small LV cavity size, and
      variation in the degree/location of LV hypertrophy. AIM: We compared results of
      MBF obtained using PMod, which permits manual segmentation, to those obtained by
      FDA-approved QPET software which has an automated segmentation algorithm.
      METHODS: 13N-ammonia PET perfusion data were acquired in list mode at rest and
      during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients
      referred for evaluation of CAD (CAD group.) Data were resampled to create static,
      ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in
      ml/min/g) were calculated using QPET and PMod softwares. RESULTS: All HCM
      patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT
      obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and
      ejection fraction. PMod yielded significantly higher values for global and
      regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was
      observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest
      MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement
      between global MBF and MFR values improved when HCM patients with high spillover
      fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress
      MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and
      QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68)
      where spillover fraction was the lowest. Unlike HCM patients, the non-HCM
      patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained
      by the two softwares, when patients with high spillover fractions were excluded
      (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). CONCLUSIONS: Anatomic
      characteristics specific to HCM hearts contribute to lower correlations between
      MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These
      differences indicate that PMod and QPET cannot be used interchangeably for
      MBF/MFR analyses in HCM patients.

PMID- 29359274
TI  - Coronary vascular age: An alternate means for predicting stress-induced
      myocardial ischemia in patients with suspected coronary artery disease.
AB  - BACKGROUND: Coronary artery calcium (CAC) can be used to estimate vascular age in
      adults, providing a convenient transformation of CAC from Agatston units into a
      year's scale. We investigated the role of coronary vascular age in predicting
      stress-induced myocardial ischemia in subjects with suspected coronary artery
      disease (CAD). METHODS: A total of 717 subjects referred to CAC scoring and 82Rb
      PET/CT stress-rest myocardial perfusion imaging for suspected CAD were studied.
      CAC score was measured according to the Agatston method and coronary vascular age
      by equating estimated CAD risk for chronological age and CAC using the formula
      39.1 + 7.25 * ln(CAC + 1). RESULTS: Stress-induced ischemia was present in 105
      (15%) patients. Mean chronological age, CAC score, and coronary vascular age were
      higher (all P < .001) in patients with ischemia compared to those without. At
      incremental analysis, the global Chi square increased from 41.26 to 68.77 (P <
      .001) when chronological age was added to clinical variables. Including vascular
      age in the model, the global Chi square further increased from 68.77 to 106.38 (P
      < .001). Adding chronological age to clinical data, continuous net
      reclassification improvement (cNRI) was 0.57, while adding vascular age to
      clinical data and chronological age cNRI was 0.62. At decision curve analysis,
      the model including vascular age was associated with the highest net benefit
      compared to the model including only clinical data, to the model including
      chronological age and clinical data, and to a strategy considering that all
      patients had ischemia. The model including vascular age also showed the largest
      reduction in false-positive rate without missing any ischemic patients.
      CONCLUSIONS: In subjects with suspected CAD, coronary vascular age is strongly
      associated with stress-induced ischemia. The communication of a given vascular
      age would have a superior emotive impact improving observance of therapies and
      healthier lifestyles.

PMID- 29359276
TI  - ?

PMID- 29359277
TI  - Response of Cerebral Blood Flow and Blood Pressure to Dynamic Exercise: A Study
      Using PET.
AB  - Dynamic exercise elicits fluctuations in blood pressure (BP) and cerebral blood
      flow (CBF). This study investigated responses in BP and CBF during cycling
      exercise and post-exercise hypotension (PEH) using positron emission tomography
      (PET). CBF was measured using oxygen-15-labeled water (H215O) and PET in 11 human
      subjects at rest (Rest), at the onset of exercise (Ex1), later in the exercise
      (Ex2), and during PEH. Global CBF significantly increased by 13% at Ex1 compared
      with Rest, but was unchanged at Ex2 and during PEH. Compared with at Rest,
      regional CBF (rCBF) increased at Ex1 (20~42%) in the cerebellar vermis,
      sensorimotor cortex for the bilateral legs (M1Leg and S1Leg), insular cortex and
      brain stem, but increased at Ex2 (28~31%) only in the vermis and M1Leg and S1Leg.
      During PEH, rCBF decreased compared with Rest (8~13%) in the cerebellum, temporal
      gyrus, piriform lobe, thalamus and pons. The areas showing correlations between
      rCBF and mean BP during exercise and PEH were consistent with the central
      autonomic network, including the brain stem, cerebellum, and hypothalamus
      (R2=0.25-0.64). The present study suggests that higher brain regions are
      coordinated through reflex centers in the brain stem in order to regulate the
      cardiovascular response to exercise.

PMID- 29359278
TI  - Effectiveness and Safety of Non-Vitamin K Oral Anticoagulants in Comparison to
      Phenprocoumon: Data from 61,000 Patients with Atrial Fibrillation.
AB  - All pivotal trials have evaluated non-vitamin K oral antagonists (NOACs) against
      warfarin. However, in some regions of the world, phenprocoumon is the most widely
      used vitamin K antagonist (VKA). There is little evidence documenting
      effectiveness and safety of NOACs compared with phenprocoumon in atrial
      fibrillation (AF). A retrospective cohort study using a German claims database
      was conducted to assess effectiveness (stroke, systemic embolism [SE]) and safety
      (bleeding leading to hospitalization) during therapy with NOACs and phenprocoumon
      in 61,205 AF patients. Hazard ratios (HRs) for effectiveness and safety outcomes
      were derived from Cox proportional hazard models, adjusting for baseline
      characteristics. Propensity score matching was performed as a sensitivity
      analysis. As a prespecified subgroup analysis, the effects of reduced NOAC dosing
      were compared with phenprocoumon. A total of 61,205 patients were identified in
      whom phenprocoumon (n = 23,823, 38.9%), apixaban (n = 10,117, 16.5%), dabigatran
      (n = 5,122, 8.4%), or rivaroxaban (n = 22,143, 36.2%) was initiated. After
      adjusting for baseline confounders, all three NOACs tested had significantly
      lower risks of stroke/SE compared with phenprocoumon (apixaban-HR: 0.77, 95% CI:
      0.66-0.90; dabigatran-HR: 0.74, 95% CI: 0.60-0.91; rivaroxaban-HR: 0.86, 95% CI:
      0.76-0.97). Apixaban (HR: 0.58, 95% CI: 0.49-0.69) and dabigatran (HR: 0.64, 95%
      CI: 0.50-0.80) were associated with lower bleeding risks than phenprocoumon,
      whereas the risk was similar for rivaroxaban and phenprocoumon. All three NOACs
      showed reduced risk of intracranial bleeding compared with phenprocoumon. Reduced
      doses of NOACs were predominantly used in patients with advanced age and
      comorbidities with generally similar effectiveness and safety benefits compared
      with phenprocumon as standard-dose NOACs.

PMID- 29359275
TI  - The Natural History of IBD: Lessons Learned.
AB  - PURPOSE OF REVIEW: Inflammatory bowel diseases (IBD), which include Crohn's
      disease (CD) and ulcerative colitis (UC), are chronic, relapsing diseases with
      unknown etiologies. The purpose of this review is to present the natural disease
      course evidenced in the latest epidemiology data. RECENT FINDINGS: The prevalence
      of IBD is rapidly increasing, affecting five million patients worldwide with the
      highest incidence observed in Northern Europe and Northern America. It has been
      shown that both CD and UC patients are at an increased risk for developing cancer
      of the gastrointestinal tract compared to the general population. Though the
      disease course of IBD is unpredictable, the rate of surgical treatment has
      declined potentially as a consequence of the introduction of immunomodulators and
      new biologic treatment options. Treatments with biological agents and/or
      immunosuppressive drugs as well as disease monitoring with eHealth devices seem
      to have a positive impact on the disease course. However, long-term follow-up
      studies are still lacking and therefore no reliable conclusions can be drawn as
      of yet. Medical compliance is paramount in the treatment of IBD, and continuous
      research focusing on approaches that increase compliance is also necessary.

PMID- 29359279
TI  - Hypothalamic-Pituitary-Adrenocortical Axis Activity in Alcohol-Dependent Patients
      During Treatment with High-Dose Baclofen.
AB  - AIMS: Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis has been
      reported to be affected in alcohol use disorder (AUD). It has been suggested that
      pharmacological relapse prevention in AUD might exert its effects partly by
      modulation of HPA axis activity. Here, we assessed the effects of high-dose
      treatment with baclofen on HPA axis activity in alcohol-dependent patients within
      a 24-week randomized, placebo-controlled trial (BACLAD study). METHODS: Plasma
      levels of copeptin, adrenocorticotropic hormone (ACTH), and cortisol were
      measured at 3 timepoints in alcohol-dependent patients during the study.
      Corresponding plasma levels in healthy controls were assessed once. RESULTS: ACTH
      blood levels were significantly higher in the group of alcohol-dependent patients
      compared to controls. In patients receiving individually titrated high-dose
      baclofen, plasma cortisol levels decreased significantly, whereas no significant
      alterations were found in the placebo group. CONCLUSIONS: Our study underlines
      again the role of HPA axis alterations in AUD. Furthermore, a decrease in
      hormonal stress levels during treatment with high-dose baclofen might contribute
      to the relapse preventive effects of this compound.

PMID- 29359280
TI  - SMFM 2018 Pregnancy Meeting: Looking Ahead to the Scientific Program (Podcast).

PMID- 29359281
TI  - Correction: Tensiomyographic Assessment of Muscle Contractile Properties in 9- to
      14-Year Old Children.

PMID- 29359282
TI  - [Health Care Organization - The New German S3-Guideline on Alcohol-Related
      Disorders and its Relevance for Health Care].
AB  - BACKGROUND: Alcohol dependence is one of the most serious diseases of addiction
      in Germany. The new S3-guideline "Screening, Diagnostics and Treatment of Alcohol
      Related Disorders" has been presented in 2015 and summarizes the present state of
      knowledge pertaining to the diagnosis and treatment of alcohol abuse and alcohol
      dependence. METHODS: This guideline was developed over four years within the
      framework of the Association of the Scientific Medical Societies in Germany
      (AWMF). The German Association for Psychiatry, Psychotherapy and Psychosomatics
      (DGPPN) and the German Society for Research and Therapy in Addiction (DG-Sucht)
      took the lead in the organization. More than 50 professional societies and
      associations and health organizations as well as more than 60 acknowledged
      experts were involved, including networks of self-help groups and relatives. The
      working group on "health care organization", whose results are presented here,
      was one out of thirteen working groups, focusing on the task how to implement the
      guideline under the basic conditions of the German health care system with its
      sectors and interfaces. RESULTS: For the chapter on "health care organization" 27
      recommendations have been consented. Many of these have been prepared by the
      respective working groups. These recommendations cover areas such as screening,
      diagnostics and short interventions, detoxification and withdrawal as well as
      pharmacotherapy, physical complications and psychic comorbidity, medical
      rehabilitation and other forms of post-acute treatment, primary care by general
      practitioners, as well as specific target groups such as children and
      adolescents, (pregnant) women and the elderly, and, in addition, self-help
      approaches. CONCLUSION: For needs-based diagnostics and treatment of alcohol
      related disorders, guideline-based recommendations for health care organization
      offer a framework for the cooperation and coordination of all health sectors and
      occupational groups, especially with respect to their interfaces. This includes
      the cooperation between the medical and the psychosocial system and stretches
      from harm reduction to social inclusion of people concerned. Particularly the
      field of rehabilitation with its explicit aims for participation relies heavily
      on such a cooperation.

PMID- 29359283
TI  - [Multilevel Analysis as a Tool to Analyze Research Questions in Rehabilitation
      Science].
AB  - Studies in rehabilitation science often investigate data representing different
      hierarchical data levels. Hierarchical sample structures prevail if single cases
      (e. g. rehabilitation patients) are grouped or are members of grouped entities or
      clusters (e. g. teams, groups, institutions), respectively. Analyzing data of
      rehabilitation patients treated in different institutions it has to be regarded
      that belonging to a specific institution (level 2; cluster-level) may be
      associated with individuals' (level 1) characteristics systematically. If
      rehabilitation patients take part in different training groups, specific
      characteristics of the training groups (level 2) may affect treatment effects of
      individuals (level 1) significantly. Multilevel analysis or hierarchical linear
      models allow for simultaneously modelling such multilevel data structures in an
      integrative and comprehensive manner. In this article it will be shown which
      specific aspects concerning hierarchical sampling procedures, data organization,
      specification of research hypotheses, statistical data analysis as well as
      interpretation of study results have be regarded to model potential clustering
      effects appropriately.

PMID- 29359284
TI  - [Change of Symptom Severity and Functioning According to ICF in the In-Patient
      Psychosomatic Rehabilitation].
AB  - BACKGROUND: In this naturalistic study the changes of patients of an in-patient
      psychosomatic rehabilitation with regard to functioning and to symptom severity
      were examined. METHODS: Self-evaluations of patients concerning their functioning
      (ICF AT-50 Psych) and their symptom severity (GSI) were elevated at 3 measurement
      periods: on admission (n=419), on discharge (n=354) and 6 months after discharge
      (n=297). RESULTS: Functioning as well as symptom severity improved from t1 to t2.
      With regard to functioning an improvement on global and specific scales was
      shown. From t2 to t3 the symptom severity increased lightly again, whereas the
      functioning level remained rather steady. Changes in symptom severity highly
      correlate with changes of functioning. DISCUSSION: The results point to the fact
      that psychosomatic rehabilitation has positive effects on functioning. While
      planning the therapy functioning as well as symptom severity should be
      considered. Controlled studies are needed.

PMID- 29359285
TI  - [Self-Determination in Medical Rehabilitation - Development of a Conceptual Model
      for Further Theoretical Discussion].
AB  - AIM: Aim was to gather theoretical knowledge about self-determination and to
      develop a conceptual model for medical rehabilitation- which serves as a basis
      for discussion. METHODS: We performed a literature research in electronic
      databases. Various theories and research results were adopted and transferred to
      the context of medical rehabilitation and into a conceptual model. RESULTS: The
      conceptual model of self-determination reflects on a continuum which forms of
      self-determination may be present in situations of medical rehabilitation
      treatments. The location on the continuum depends theoretically on the
      manifestation of certain internal and external factors that may influence each
      other. CONCLUSIONS: The model provides a first conceptualization of self
      determination focusing on medical rehabilitation which should be further refined
      and tested empirically.

PMID- 29359286
TI  - [Systemic Diseases with Kidney Involvement].

PMID- 29359287
TI  - [83-Year-Old Man with Prolonged Epigastric Pain and Ultimately Vomiting].

PMID- 29359288
TI  - [Renal manifestation in ANCA-associated vasculitis].
AB  - In patients with ANCA-associated vasculitis renal involvement is frequently seen
      and the severity of renal manifestation is very important for therapeutic
      strategies and prognosis. Clinically rapid loss of renal function, nephritic
      sediment and proteinuria in a non-nephrotic range are characterizing a focal
      segmental necrotizing pauci-immune glomerulonephritis with extrarenal
      proliferations. Induction treatment depends on the severity of manifestations.
      With a normal renal function methotrexate can be used in combination with
      steroids. In patients with organ threatening involvement but creatinine below 500
      umol/l cyclophosphamide pulses or Rituximab should be used together with
      steroids, initially with i. v. pulses. Rituximab is more effective in PR3-ANCA
      vasculitis and should be used in relapsing disease, in young patients to avoid
      gonadal toxicity and in patients with an increased risk of malignancies. In
      patients on dialysis or with creatinine > 500 umol/l plasma exchange should be
      added. Maintenance treatment (mainly with azathioprine) is necessary as at least
      50 % of the patients develop relapses. Rituximab seems more effective, however it
      is not approved for maintenance treatment and no long-term data are available.
      Adjuvant treatment, long-term side effects and the increased incidence of
      cardiovascular events have to be included in the follow-up of vasculitis
      patients. In end-stage renal disease patients relapses occur but are more
      difficult to diagnose and treat with higher incidence of infections.
      Transplantation should be offered as patient and transplant survival is good.

PMID- 29359289
TI  - [Renal Involvement in Connective Tissue Diseases].
AB  - Renal involvement is common and heterogenous in connective tissue diseases and
      has a main influence on prognosis and mortality. In systemic lupus erythematosus
      proliferative glomerulonephritis is the most common manifestation, while in
      primary Sjogren's syndrome interstitial nephritis with tubular dysfunction is the
      predominant pathological feature. In systemic sclerosis the most serious renal
      manifestation is scleroderma renal crisis characterized by abrupt onset of
      hypertension and acute kidney injury associated with an increase in plasma renin
      activity. Risk factors for scleroderma renal crisis are diffuse cutaneous
      involvement, treatment with corticosteroids > 15 mg prednisolone/day and
      treatment with calcineurin inhibitors.Regular measurement of urine sediment,
      proteinuria-to-urine creatinine ratio, tubular proteinuria, measurement of plasma
      creatinine, and office as well as home blood pressure monitoring are strongly
      recommended. Diagnostic kidney biopsy is essential in differentiating the
      different types of lupus nephritis and renal involvement in sjogren's
      syndrome.The optimal treatment of lupus nephritis varies with the classification
      of the morphological findings present on renal biopsy. The treatment of
      interstitial nephritis in sjogren's syndrome consists of immunosuppression e. g.
      corticosteroids. Renal tubular acidosis should be corrected by sodium alkali and
      potassium alkali. Angiotensin-converting enzyme inhibitors play a major role in
      the treatment of scleroderma renal crisis, they should be continued also in
      patients progressing to end-stage renal disease.

PMID- 29359290
TI  - [Renal involvement in amyloidosis and sarcoidosis].
AB  - Amyloidosis is a rare disease characterized by extracellular deposition of
      fibrils. Among the most common forms of systemic amyloidosis with renal
      involvement are AL-amyloidosis based on plasma cell dyscrasia and AA-amyloidosis
      in chronic inflammatory diseases. Depending on the affected renal compartment,
      the clinical appearance of renal amyloidosis varies. The pattern of renal amyloid
      deposition can be glomerular, interstitial, tubular or even vascular. Renal
      amyloid deposits are detected by renal biopsy. Patients with glomerular deposits
      typically show severe nephrotic syndrome with volume overload. Patients with
      predominantly tubulo-interstitial or vascular deposits typically exhibit lower
      proteinuria and progressive renal impairment. Treatment strategies for renal
      amyloidosis are primarily based on the treatment of the underlying disease
      including chemotherapy or stem cell transplantation in AL-amyloidosis or
      treatment of chronic inflammatory diseases in AA-amyloidosis. Granulomatous
      interstitial nephritis is the most common renal lesion occurring in sarcoidosis.
      Therapy of granulomatous interstitial nephritis is mainly based on the use of
      glucocorticoids.

PMID- 29359291
TI  - [Granulated Proctosigmoiditis by Antibiotic-associated Infection with Pseudomonas
      Aeruginosa].
AB  - HISTORY AND ADMISSION FINDINGS:  We report on the case of an elderly patient with
      persisting diarrhea. Few weeks previous of admission the patient had received
      antibiotic therapy because of respiratory infection. On admission he seemed
      exsiccated and feeble. EXAMINATIONS:  Macroscopic findings in colonoscopy showed
      proctosigmoiditis and membranous exsudations. Stool culture provided the evidence
      for an antibiotic-associated infection with pseudomonas aeruginosa. TREATMENT AND
      COURSE:  The recommended oral therapy with ciprofloxacin proved to be effective.
      CONCLUSION:  Complications with elderly patients are multimorbidity and diarrhea
      induced prerenal failure. Frail patients can react strongly to antibiotic therapy
      with enteritis and dysbacteriosis.

PMID- 29359292
TI  - [Prevention and Screening in Colorectal Cancer].

PMID- 29359293
TI  - [NOAKs in Obese Patients - No Problem?]

PMID- 29359294
TI  - Detection and Quantification of Cannabinoids in Extracts of Cannabis sativa Roots
      Using LC-MS/MS.
AB  - A liquid chromatography-tandem mass spectrometry single-laboratory validation was
      performed for the detection and quantification of the 10 major cannabinoids of
      cannabis, namely, (-)-trans-Delta9-tetrahydrocannabinol, cannabidiol,
      cannabigerol, cannabichromene, tetrahydrocannabivarian, cannabinol, (-)-trans
      Delta8-tetrahydrocannabinol, cannabidiolic acid, cannabigerolic acid, and Delta9
      tetrahydrocannabinolic acid-A, in the root extract of Cannabis sativa.
      Acetonitrile : methanol (80 : 20, v/v) was used for extraction; d3-cannabidiol
      and d3- tetrahydrocannabinol were used as the internal standards. All 10
      cannabinoids showed a good regression relationship with r2 > 0.99. The validated
      method is simple, sensitive, and reproducible and is therefore suitable for the
      detection and quantification of these cannabinoids in extracts of cannabis roots.
      To our knowledge, this is the first report for the quantification of cannabinoids
      in cannabis roots.

PMID- 29359295
TI  - Impact of Duration of Perioperative Ischemia on Outcomes of Microsurgical
      Reconstructions.
AB  - BACKGROUND:  Free tissue transfers have become routine for a variety of
      reconstructive purposes. During the time of transfer, some period of ischemia
      time is unavoidable, causing structural and metabolic changes. This study aimed
      to evaluate whether length of intraoperative ischemia affects the outcomes of
      microsurgical reconstructions. METHODS:  Within a 7-year period, 638 patients
      having undergone 690 microvascular free flap reconstructions fulfilled inclusion
      criteria for this study. The data were retrospectively screened for patients'
      demographics, intra- and perioperative details, flap survival, surgical
      complications, and outcomes. The cases were divided into two groups according to
      the length of intraoperative ischemia time, "< 60" versus ">= 60 minutes."
      RESULTS:  Both groups were comparable regarding the patient constellation,
      comorbidities, smoking status, and perioperative characteristics. Operative times
      were significantly longer in patients which had ischemia times of >= 60 minutes
      (p < 0.05). Also, during our 3-month follow-up period, a significantly higher
      rate of major and minor surgical complications, including total and partial flap
      losses, as well as higher revision rates occurred in the >= 60 minutes ischemia
      time group (p < 0.05). CONCLUSION:  In this study, prolonged ischemia time during
      free flap reconstructions was associated with higher rates of revision surgeries
      and complications rates.

PMID- 29359296
TI  - Histological Changes in the Rat Femoral Artery Following the Use of the Empty-and
      Refill Test.
AB  - BACKGROUND:  This study examines the effects of the empty-and-refill patency test
      on rat femoral arteries in the longer postoperative time period. METHODS:  A
      simple arterial anastomosis was performed bilaterally on 20 rats. The empty-and
      refill test was performed unilaterally in all rats, leaving the contralateral
      artery as an internal control. Rats were divided into two cohorts of 10 rats and
      survived for 48 hours and 2 weeks. Vessel patency was assessed prior to closing
      and immediately prior to sacrifice. The femoral arteries were harvested
      bilaterally and hematoxylin and eosin stains were performed. The femoral artery
      distal to the anastomosis in the region of the empty-and-refill test was
      histologically evaluated. RESULTS:  All vessels were patent at the time of
      sacrifice. There was no statistical difference in the numeric scoring between the
      experimental and control vessels in the 48-hour cohort. Almost all vessels
      harvested at 48 hours showed endothelial cell loss distal to the anastomosis
      regardless of whether they underwent the empty-and-refill test. The only
      statistically significant difference in the 2-week cohort was an increase in
      adventitial smooth muscle proliferation in the experimental group. There were no
      other statistically significant results between the experimental and control
      groups at 2 weeks. An overall comparison of both cohorts revealed a statistically
      significant increase in endothelial cell number and intimal proliferation by 2
      weeks postsurgery. CONCLUSION:  The empty-and-refill test does not compromise rat
      femoral artery anastomotic patency, nor does it produce histological damage
      either 48 hours or 2 weeks postsurgery.

PMID- 29359297
TI  - Correction: Prevalence of Urinary Incontinence in Females Performing High-Impact
      Exercises.

PMID- 29359298
TI  - Recent Advances in Cell Electrospining of Natural and Synthetic Nanofibers for
      Regenerative Medicine.
AB  - The progression of nanotechnology provides opportunities to manipulate synthetic
      and natural materials to mimic the natural structure for tissue engineering
      applications. The electrospinning technique applies electrostatic principle to
      fabricate electrospun nanofibers. Nanofiber scaffolds are precisely similar to
      the native extracellular matrix (ECM) and support cell proliferation, adhesion,
      tendency to preserve their phenotypic shape and directed growth according to the
      nanofiber direction. This study reviewed both the natural and synthetic type of
      nanofibers and described the different properties used to trigger certain process
      in the tissue development. Also, the potential applications of electrospun
      scaffolds for regenerative medicine were summarized.

PMID- 29359299
TI  - Comparing the Efficacy of the Total Stabilizing and Posterior Stabilizing Knee
      Prostheses in Obese and Preobese Females: A Retrospective Cohort Study.
AB  - Obesity is associated with increased surgical complications that may lead to
      suboptimal total knee arthroplasty (TKA) outcomes. Additionally, females exhibit
      increased rates of severe, clinical osteoarthritis OA, along with increased
      ligamentous laxity. Therefore, obese females present a particularly challenging
      case for TKA with increased joint loads coupled with a propensity for
      instability. This study retrospectively analyzed knee range of motion and
      stability of one TKA designs with two different degrees of polyethylene
      conformity in the obese female population. The implants (Stryker Triathlon total
      stabilizing [TS] and Stryker Triathlon posterior stabilizing [PS]) differ in
      their level of constraint, with the TS being more constrained. We hypothesized
      that the TS implants would be associated with improved functional outcomes in the
      obese female population, secondary to increased coronal stability to offset the
      ligamentous laxity. Of 482 knees reviewed, 173 met the inclusion criteria of:
      female, body mass index (BMI) >= 25, receiving TS (N = 93), or PS (N = 8).
      Primary knee outcome measures were: active flexion, passive flexion, active
      extension, passive extension, and stability at 0 degrees  and 30 degrees 
      flexion. These factors were statistically analyzed at preop, 2-week, 6-week, 3
      month, and 1-year time points. Preoperatively, the TS cohort was significantly
      higher in BMI and knee laxity, potentially starting this cohort at a functional
      disadvantage. Postoperatively, the TS implant was associated with a statistically
      significant early improvement in active and passive knee extension. There was no
      longer any significant difference in knee laxity postop. Our data support the
      hypothesis that obese females may benefit from the increased stability afforded
      by the TS design.

PMID- 29359300
TI  - Acute Care Management of Stroke.

PMID- 29359301
TI  - Clinical Application of Flexible Endoscopic Evaluation of Swallowing in Stroke.
AB  - This article aims to review the use of laryngoscopy to assess swallowing function
      in the stroke population. Since its inception in 1988, fiberoptic endoscopic
      evaluation of swallowing (FEES) has become an established procedure with distinct
      objective findings and practical applications, enabling many to choose it as the
      primary instrumental tool in evaluating poststroke dysphagia. In this article, we
      outline the decision-making process of when to use FEES. We highlight
      considerations for the acute stroke patient and visual signs that guide decision
      making during a FEES, such as secretions, swallowing frequency, and pharyngeal
      squeeze elicitation. The application of the ice chip protocol for stroke patients
      who have been nil per os is discussed, along with common observable events on
      FEES performed on stroke patients like a delay, penetration/aspiration, and bolus
      retention. Finally, we briefly review testing interventions and follow-up
      readiness with FEES.

PMID- 29359302
TI  - Dysarthria following Stroke.
AB  - Dysarthria is a common consequence of stroke and can have a detrimental influence
      on communication and quality of life. Speech-language pathologists (SLPs) play an
      important role in the evaluation and rehabilitation of stroke survivors who
      present with dysarthria. An understanding of the physiologic reason behind the
      altered speech characteristics, such as weakness or incoordination, can
      facilitate differential diagnosis, guide evaluation strategies, and influence
      treatment approaches. An initial comprehensive speech evaluation is comprised of
      examination of the speech mechanism, screening of speech subsystems, perceptual
      assessment, and intelligibility measurement. Management strategies focus on
      optimizing communication through compensatory strategies as well as providing
      physiologic support. The SLP is also responsible for educating family and staff
      regarding strategies that can facilitate communication.

PMID- 29359304
TI  - Implementing a Standardized Assessment Battery for Aphasia in Acute Care.
AB  - In this article, the implementation of a standardized assessment battery for the
      evaluation of language in an acute care setting is described. Following an
      institutional shift to adopt electronic medical records, researchers and
      clinicians worked together to develop a technology-assisted evaluation of aphasia
      that would be used to assess all patients admitted to our facility with stroke.
      The project goal was to devise a clinical process to improve aphasia diagnosis
      and evaluation while remaining feasible within constraints imposed by the acute
      care setting and the electronic medical record. Utilizing frameworks from
      implementation science, the four key phases were: (1) initial considerations of
      the host setting, (2) creation of a structure for implementation, (3) maintenance
      of this structure once implementation began, and (4) improvement for future
      applications. A pilot implementation demonstrated that establishing and executing
      a minimum standardized assessment for aphasia in acute care is feasible.
      Retrospective medical record review of 50 aphasia evaluations in the setting of
      first incidence of left hemisphere stroke affecting the middle cerebral artery
      (25 preimplementation and 25 postimplementation) revealed that information
      content of medical notes was more consistent and complete postimplementation than
      preimplementation. Clinical implications and future directions are discussed.

PMID- 29359303
TI  - Contemporary Approaches to the Management of Post-stroke Apraxia of Speech.
AB  - Apraxia of speech (AOS) is a motor speech disorder that disrupts the planning and
      programming of speech motor movements. In the acute stage of stroke recovery, AOS
      following unilateral (typically) left hemisphere stroke can occur alongside
      dysarthria, an impairment in speech execution and control, and/or aphasia, a
      higher-level impairment in language function. At this time, perceptual evaluation
      (the systematic, although subjective, description of speech and voice
      characteristics) is perhaps the only "gold standard" for differential diagnosis
      when it comes to motor speech disorders. This poses a challenge for speech
      language pathologists charged with the evaluation of poststroke communication
      abilities, as distinguishing production impairments associated with AOS from
      those that can occur in aphasia and/or dysarthria can be difficult, especially
      when more than one deficit is present. Given the need for more objective,
      reliable methods to identify and diagnose AOS, several studies have turned to
      acoustic evaluation and neuroimaging to supplement clinical assessment. This
      article focuses on these recent advances. Studies investigating acoustic
      evaluation of AOS will be reviewed, as well as those that have considered the
      extent that neuroimaging can guide clinical decision making. Developments in the
      treatment of AOS will also be discussed. Although more research is needed
      regarding the use of these methods in everyday clinical practice, the studies
      reviewed here show promise as emerging tools for the management of AOS.

PMID- 29359305
TI  - Providing Effective Speech-Language Pathology Group Treatment in the
      Comprehensive Inpatient Rehabilitation Setting.
AB  - Group treatment is an integral part of speech-language pathology (SLP) practice.
      The majority of SLP literature concerns group treatment provided in outpatient
      settings. This article describes the goals, procedures, and benefits of providing
      quality SLP group therapy in the comprehensive inpatient rehabilitation (CIR)
      setting. Effective CIR groups must be designed with attention to type and
      severity of communication impairment, as well physical stamina of group members.
      Group leaders need to target individualized patient goals while creating a
      challenging, complex, and dynamic group context that supports participation by
      all group members. Direct patient-to-patient interaction is fostered as much as
      possible. Peer feedback supports goal acquisition by fellow group members. The
      rich, complex group context fosters improved insight, initiation, social
      connectedness, and generalization of communication skills. Group treatment
      provides a unique type of treatment not easily replicated with individual
      treatment. SLP group treatment in a CIR is an essential component of an
      intensive, high-quality program. Continued advocacy for group therapy provision
      and research into its efficacy and effectiveness are warranted.

PMID- 29359306
TI  - Contributions of Neuroimaging to Understanding Language Deficits in Acute Stroke.
AB  - Advances in structural and functional imaging techniques have provided new
      insights into our understanding of brain and language relationships. In this
      article, we review the various structural and functional imaging methods
      currently used to study language deficits in acute stroke. We also discuss the
      advantages and the limitations of each imaging modality and the applications of
      each modality in the clinical and research settings in the study of language
      deficits.

PMID- 29359307
TI  - Regional Brain Dysfunction Associated with Semantic Errors in Comprehension.
AB  - Here we illustrate how investigation of individuals acutely after stroke, before
      structure/function reorganization through recovery or rehabilitation, can be
      helpful in answering questions about the role of specific brain regions in
      language functions. Although there is converging evidence from a variety of
      sources that the left posterior-superior temporal gyrus plays some role in spoken
      word comprehension, its precise role in this function has not been established.
      We hypothesized that this region is essential for distinguishing between
      semantically related words, because it is critical for linking the spoken word to
      the complete semantic representation. We tested this hypothesis in 127
      individuals with 48 hours of acute ischemic stroke, before the opportunity for
      reorganization or recovery. We identified tissue dysfunction (acute infarct
      and/or hypoperfusion) in gray and white matter parcels of the left hemisphere,
      and we evaluated the association between rate of semantic errors in a word
      picture verification tasks and extent of tissue dysfunction in each region. We
      found that after correcting for lesion volume and multiple comparisons, the rate
      of semantic errors correlated with the extent of tissue dysfunction in left
      posterior-superior temporal gyrus and retrolenticular white matter.

PMID- 29359309
TI  - Lung Adenocarcinoma Invasiveness Risk in Pure Ground-Glass Opacity Lung Nodules
      Smaller than 2 cm.
AB  - BACKGROUND:  We aimed to identify clinicopathologic characteristics and risk of
      invasiveness of lung adenocarcinoma in surgically resected pure ground-glass
      opacity lung nodules (GGNs) smaller than 2 cm. METHODS:  Among 755 operations for
      lung cancer or tumors suspicious for lung cancer performed from 2012 to 2016, we
      retrospectively analyzed 44 surgically resected pure GGNs smaller than 2 cm in
      diameter on computed tomography (CT). RESULTS:  The study group was composed of
      36 patients including 11 men and 25 women with a median age of 59.5 years (range,
      34-77). Median follow-up duration of pure GGNs was 6 months (range, 0-63). Median
      maximum diameter of pure GGNs was 8.5 mm (range, 4-19). Pure GGNs were resected
      by wedge resection, segmentectomy, or lobectomy in 27 (61.4%), 10 (22.7%), and 7
      (15.9%) cases, respectively. Pathologic diagnosis was atypical adenomatous
      hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma (MIA), or
      invasive adenocarcinoma (IA) in 1 (2.3%), 18 (40.9%), 15 (34.1%), and 10 (22.7%)
      cases, respectively. The optimal cutoff value for CT-maximal diameter to predict
      MIA or IA was 9.1 mm. In multivariate analyses, maximal CT-maximal diameter of
      GGNs >=10 mm (odds ratio, 24.050; 95% confidence interval, 2.6-221.908; p =
      0.005) emerged as significant independent predictor for either MIA or IA.
      Estimated risks of MIA or IA were 37.2, 59.3, 78.2, and 89.8% at maximal GGN
      diameters of 5, 10, 15, and 20 mm, respectively. CONCLUSION:  Pure GGNs were
      highly associated with lung adenocarcinoma in surgically resected cases, while
      estimated risk of GGNs invasiveness gradually increased as maximal diameter
      increased.

PMID- 29359308
TI  - Impaired Recognition of Emotional Faces after Stroke Involving Right Amygdala or
      Insula.
AB  - Despite its basic and translational importance, the neural circuitry supporting
      the perception of emotional faces remains incompletely understood. Functional
      imaging studies and chronic lesion studies indicate distinct roles of the
      amygdala and insula in recognition of fear and disgust in facial expressions,
      whereas intracranial encephalography studies, which are not encumbered by
      variations in human anatomy, indicate a somewhat different role of these
      structures. In this article, we leveraged lesion-mapping techniques in
      individuals with acute right hemisphere stroke to investigate lesions associated
      with impaired recognition of prototypic emotional faces before significant neural
      reorganization can occur during recovery from stroke. Right hemisphere stroke
      patients were significantly less accurate than controls on a test of emotional
      facial recognition for both positive and negative emotions. Patients with right
      amygdala or anterior insula lesions had significantly lower scores than other
      right hemisphere stroke patients on recognition of angry and happy faces. Lesion
      volume within several regions, including the right amygdala and anterior insula,
      each independently contributed to the error rate in recognition of individual
      emotions. Results provide additional support for a necessary role of the right
      amygdala and anterior insula within a network of regions underlying recognition
      of facial expressions, particularly those that have biological importance or
      motivational relevance and have implications for clinical practice.

PMID- 29359310
TI  - [Computer based neurocognitive testing in audiology].
AB  - INTRODUCTION: Due to the demographic changes neurocognition has become an
      important issue also in the field of hearing rehabilitation. BACKGROUND: The
      present study aimed to evaluate the feasibility of a neurocognitive test using
      computer based tasks with regard to the elderly with and without hearing loss and
      its practicability for the daily clinical ENT setting. PATIENTS: 171 patients of
      both genders with normal hearing or a profound hearing loss were enrolled in the
      study: 90 middleaged persons were between 50 and 64 years (57.0 +/- 4.5 years)
      and 81 elderly persons 65 years and older (72.5 +/- 5.4). METHOD: A set of
      computer-based neurocognitive tasks with only visual instructions covering
      attention, processing speed, short- and longterm memory as well as executive
      functions was applied. A presession under the supervision of a trained assistant
      was included. RESULTS: All patients were capable to complete the assessment by
      themselves regardless of age and hearing status, however the hearing impaired
      required 15 minutes more to finish the pretest and reported about a higher level
      of effort than normal hearing subjects (71 % versus 63 %). Interestingly 90 % of
      the older individuals claimed the test to fit with all ages, whereas 30 % of the
      middleaged participants remained skeptical (p = 0.02). CONCLUSION: The presented
      neurocognitive assessment might be a useful instrument which can be easily
      included into the daily clinical ENT. It may give important hints to the
      otolaryngologist in order to develop the most effective hearing rehabilitation
      strategy.

PMID- 29359311
TI  - Protective effects of the pericellular matrix of chondrocyte on articular
      cartilage against the development of osteoarthritis.
AB  - Understanding the pathogenesis of osteoarthritis (OA) provides invaluable
      information in the search of therapeutic targets for the development of disease
      modifying OA drugs. Emerging results from investigations demonstrate that the
      pericellular matrix of chondrocytes plays important roles in protecting articular
      cartilages from being degraded. Thus, maintaining the structural integrity of the
      pericellular matrix may be an effective approach to prevent the development of
      osteoarthritic joints. In this review article, we discuss the consequences of
      lacking one or more components of the pericellular matrix, and biological effects
      of the destruction of the pericellular matrix in the development of OA. We
      believe that more attention should be directed towards the pericellular matrix
      for the identification of novel biomarkers and therapeutic targets for the
      prevention and treatment of OA.

PMID- 29359312
TI  - Impact of the IADPSG criteria for gestational diabetes, and of obesity, on
      pregnancy outcomes.
AB  - BACKGROUND: The adoption of the International Association of Diabetes Study
      Groups (IADPSG) criteria for gestational diabetes mellitus (GDM) in Australia has
      been controversial. Obesity in pregnancy is also a growing concern. AIMS: To
      assess the impact of IADPSG criteria on the incidence of GDM and pregnancy
      outcomes, and to compare this to the effect of obesity, particularly among women
      who would not have GDM by the Australasian Diabetes in Pregnancy Society 1998
      criteria (ADIPS1998). MATERIAL AND METHODS: A retrospective observational cohort
      study linking results of 75 g glucose tolerance tests with demographic and
      pregnancy data was conducted. RESULTS: In our cohort of 6175 pregnancies, GDM was
      present in 926 (15%) women by the ADIPS1998 criteria; it increased to 1098
      (17.8%) women by the IADPSG criteria. Among the 5248 pregnancies which did not
      meet the ADIPS1998 criteria and were not treated for GDM, women with IADPSG GDM
      had increased risk of gestational hypertension, pre-eclampsia, induction of
      labour (IOL), primary caesarean section (PCS) and large for gestational age (LGA)
      compared to women without GDM (all P < 0.05), whereas obese women had increased
      risk of gestational hypertension, pre-eclampsia, IOL, PCS, small for gestational
      age (SGA) and shoulder dystocia compared to women of normal weight (all P <
      0.05). On multivariate analysis, IADPSG GDM was an independent risk factor only
      for IOL (P = 0.04) and LGA (<0.001). Obesity was an independent risk factor for
      gestational hypertension, pre-eclampsia, IOL, PCS, shoulder dystocia and SGA (all
      P < 0.001). CONCLUSIONS: Within our population, of women who are not currently
      treated for GDM, obesity is associated with greater pregnancy risk than GDM
      diagnosed by IADPSG criteria.

PMID- 29359313
TI  - Adding a PECS II block for proximal arm arteriovenous access - a randomised
      study.
AB  - BACKGROUND: Brachial plexus block is often utilised for proximal arm
      arteriovenous access creation. However, the medial upper arm and axilla are often
      inadequately anaesthetised, requiring repeated, intraoperative local anaesthetic
      supplementation, or conversion into general anaesthesia. We hypothesised that the
      addition of a PECS II block would improve anaesthesia and analgesia for proximal
      arm arteriovenous access surgery. METHODS: In this prospective, double-blinded,
      randomised proof-of-concept study, 36 consenting adults with end-stage renal
      disease aged between 21 and 90 years received either a combined supraclavicular
      and PECS II block (Group PECS, n = 18), or combined supraclavicular and sham
      block (Group SCB, n = 18) for proximal arm arteriovenous access surgery. Primary
      outcome was whether patients required intraoperative local anaesthetic
      supplementation by the surgeon. RESULTS: In Group PECS, 33.3% (6/18) needed local
      anaesthetic supplementation vs. 100% (18/18) in Group SCB. Group SCB had three
      times (RR 3.0, 95% CI 1.6-5.8; P < 0.001) the risk of requiring intraoperative
      local anaesthetic supplementation. Group PECS required lower volume of
      supplemental local anaesthetic compared to Group SCB (0.0 ml, IQR 0.0-6.3 ml vs.
      15.0 ml, IQR 7.4-17.8 ml; P < 0.001). Group SCB had twice [RR 2.2, 95% CI 1.1
      4.4; (P = 0.019)] the risk of needing additional sedation or analgesia. There
      were no significant differences between the groups with respect to postoperative
      visual analogue scale pain scores, time to first rescue analgesia or patient
      satisfaction. CONCLUSION: The results suggest that adding a PECS II block to a
      supraclavicular block improves regional anaesthesia for patients with end-stage
      renal disease undergoing proximal arm arteriovenous access surgery.

PMID- 29359314
TI  - A utility-based design for randomized comparative trials with ordinal outcomes
      and prognostic subgroups.
AB  - A design is proposed for randomized comparative trials with ordinal outcomes and
      prognostic subgroups. The design accounts for patient heterogeneity by allowing
      possibly different comparative conclusions within subgroups. The comparative
      testing criterion is based on utilities for the levels of the ordinal outcome and
      a Bayesian probability model. Designs based on two alternative models that
      include treatment-subgroup interactions are considered, the proportional odds
      model and a non-proportional odds model with a hierarchical prior that shrinks
      toward the proportional odds model. A third design that assumes homogeneity and
      ignores possible treatment-subgroup interactions also is considered. The three
      approaches are applied to construct group sequential designs for a trial of
      nutritional prehabilitation versus standard of care for esophageal cancer
      patients undergoing chemoradiation and surgery, including both untreated patients
      and salvage patients whose disease has recurred following previous therapy. A
      simulation study is presented that compares the three designs, including
      evaluation of within-subgroup type I and II error probabilities under a variety
      of scenarios including different combinations of treatment-subgroup interactions.

PMID- 29359315
TI  - Children's Early Decontextualized Talk Predicts Academic Language Proficiency in
      Midadolescence.
AB  - This study examines whether children's decontextualized talk-talk about
      nonpresent events, explanations, or pretend-at 30 months predicts seventh-grade
      academic language proficiency (age 12). Academic language (AL) refers to the
      language of school texts. AL proficiency has been identified as an important
      predictor of adolescent text comprehension. Yet research on precursors to AL
      proficiency is scarce. Child decontextualized talk is known to be a predictor of
      early discourse development, but its relation to later language outcomes remains
      unclear. Forty-two children and their caregivers participated in this study. The
      proportion of child talk that was decontextualized emerged as a significant
      predictor of seventh-grade AL proficiency, even after controlling for
      socioeconomic status, parent decontextualized talk, child total words, child
      vocabulary, and child syntactic comprehension.

PMID- 29359316
TI  - The Myth of Universal Sensitive Responsiveness: Comment on Mesman et al. (2017).
AB  - This article considers claims of Mesman et al. (2017) that sensitive
      responsiveness as defined by Ainsworth, while not uniformly expressed across
      cultural contexts, is universal. Evidence presented demonstrates that none of the
      components of sensitive responsiveness (i.e., which partner takes the lead, whose
      point of view is primary, and the turn-taking structure of interactions) or
      warmth are universal. Mesman and colleagues' proposal that sensitive
      responsiveness is "providing for infant needs" is critiqued. Constructs
      concerning caregiver quality must be embedded within a nexus of cultural logic,
      including caregiving practices, based on ecologically valid childrearing values
      and beliefs. Sensitive responsiveness, as defined by Mesman and attachment
      theorists, is not universal. Attachment theory and cultural or cross-cultural
      psychology are not built on common ground.

PMID- 29359317
TI  - Modeling survival distribution as a function of time to treatment
      discontinuation: A dynamic treatment regime approach.
AB  - We consider estimating the effect that discontinuing a beneficial treatment will
      have on the distribution of a time to event clinical outcome, and in particular
      assessing whether there is a period of time over which the beneficial effect may
      continue after discontinuation. There are two major challenges. The first is to
      make a distinction between mandatory discontinuation, where by necessity
      treatment has to be terminated and optional discontinuation which is decided by
      the preference of the patient or physician. The innovation in this article is to
      cast the intervention in the form of a dynamic regime "terminate treatment
      optionally at time v unless a mandatory treatment-terminating event occurs prior
      to v" and consider estimating the distribution of time to event as a function of
      treatment regime v. The second challenge arises from biases associated with the
      nonrandom assignment of treatment regimes, because, naturally, optional treatment
      discontinuation is left to the patient and physician, and so time to
      discontinuation may depend on the patient's disease status. To address this
      issue, we develop dynamic-regime Marginal Structural Models and use inverse
      probability of treatment weighting to estimate the impact of time to treatment
      discontinuation on a time to event outcome, compared to the effect of not
      discontinuing treatment. We illustrate our methods using the IMPROVE-IT data on
      cardiovascular disease.

PMID- 29359318
TI  - Reply to the letter 'A brief comment about predictive models for mortality in
      intensive care units'.

PMID- 29359319
TI  - Subtype classification and heterogeneous prognosis model construction in
      precision medicine.
AB  - Common diseases including cancer are heterogeneous. It is important to discover
      disease subtypes and identify both shared and unique risk factors for different
      disease subtypes. The advent of high-throughput technologies enriches the data to
      achieve this goal, if necessary statistical methods are developed. Existing
      methods can accommodate both heterogeneity identification and variable selection
      under parametric models, but for survival analysis, the commonly used Cox model
      is semiparametric. Although finite-mixture Cox model has been proposed to address
      heterogeneity in survival analysis, variable selection has not been incorporated
      into such semiparametric models. Using regularization regression, we propose a
      variable selection method for the finite-mixture Cox model and select important,
      subtype-specific risk factors from high-dimensional predictors. Our estimators
      have oracle properties with proper choices of penalty parameters under the
      regularization regression. An expectation-maximization algorithm is developed for
      numerical calculation. Simulations demonstrate that our proposed method performs
      well in revealing the heterogeneity and selecting important risk factors for each
      subtype, and its performance is compared to alternatives with other regularizers.
      Finally, we apply our method to analyze a gene expression dataset for ovarian
      cancer DNA repair pathways. Based on our selected risk factors, the prognosis
      model accounting for heterogeneity consistently improves the prediction for the
      survival probability in both training and test datasets.

PMID- 29359320
TI  - Refining remission evaluation in MDS with isolated del(5q).

PMID- 29359321
TI  - Acute-onset Restless legs syndrome in acute neurological conditions-a prospective
      study on patients with the Guillain-Barre syndrome and acute stroke.
AB  - OBJECTIVES: While the Restless legs syndrome (RLS) is usually recognized as a
      chronic condition, it has often been diagnosed among patients with acute
      neurological illnesses, in which limb discomfort is reported. This study was
      conducted to determine how many among these, actually have acute-onset RLS, and
      also to evaluate characteristics of this subgroup of patients with Guillain-Barre
      syndrome (GBS) and stroke developing acute-onset RLS. METHODS: Consecutive
      patients diagnosed with GBS and eligible stroke patients, admitted to our
      Neurology services over a 1-year period, were enrolled. They were evaluated for
      symptoms of RLS based on IRLSSG consensus criteria and the AIIMS RLS
      Questionnaire for Indian patients (ARQIP). RESULTS: Forty adults with GBS and 58
      with stroke were included. A total of 10 of the 40 (25%) patients with GBS
      developed definite acute RLS, which was mostly monophasic. Seven (70%) of these
      had demyelinating type of GBS, a significant association with acute RLS (P =
      .024). Six of the 58 stroke patients (10%) developed definite acute-onset, often
      persistent RLS. Subcortical location showed significant association with
      increased risk of developing acute RLS (P < .001). All patients diagnosed with
      acute-onset RLS had an immediate and good response to dopamine agonists.
      CONCLUSION: This is the first study showing that acute-onset RLS is common,
      affecting nearly 25% of patients with GBS and 10% patients with acute stroke.
      Recognizing and treating it can majorly contribute toward symptom relief and
      early improvement in the quality of life for this population.

PMID- 29359322
TI  - Evolution of bias and sample size in postoperative pain management trials after
      hip and knee arthroplasty.
AB  - BACKGROUND: Bias (systematic error) and small trial sample size (random error)
      may induce imprecise and exaggerated treatment effects in randomised controlled
      trials (RCTs). To avoid this, SPIRIT- and CONSORT-guidelines, and Cochrane
      Collaboration bias recommendations were developed. We investigated risk of bias
      and trial sample size development over time in postoperative pain trials.
      METHODS: This study was based on data from two systematic reviews regarding pain
      management after total hip arthroplasty (THA) or total knee arthroplasty (TKA).
      RCTs of analgesic interventions with a comparator control group were included.
      Primary outcomes were risk of bias and trial sample size developments over time.
      We calculated cumulated bias scores ranging from 0 to 14 based on Cochrane's
      seven bias domains (0 = low; 1 = unclear, 2 = high). Developments were evaluated
      with run and control charts. Further, we compared data from trials published
      between 1990-1999 and 2010-2016. RESULTS: We included 171 trials published
      between 1989 and 2016. Overall, the summarised risk of bias decreased, mainly due
      to better randomization and allocation concealment. Visual inspection suggested
      an on-going improvement that started around 2007. Trial sample size did not
      change significantly. For trials published between 1990-1999 and 2010-2016
      adequate reporting increased from 36% to 75% for random sequence generation, from
      9% to 38% for allocation concealment and from 27% to 52% for blinding of
      participants/personnel. CONCLUSION: Risk of bias for RCTs regarding postoperative
      pain management after THA and TKA has decreased from 2007 to 2016, mainly due to
      better randomization and allocation concealment. Deficiencies remain. Thus,
      reporting according to validated guidelines is essential. Sample sizes did not
      change significantly.

PMID- 29359323
TI  - Right of reply to: Surgical treatment is an excellent option for women with
      endometriosis and infertility.

PMID- 29359324
TI  - Clinical study of hereditary ovarian cancer syndrome in Shandong province, East
      China.
AB  - OBJECTIVE: To explore the clinicopathologic characteristics and prognosis of
      hereditary ovarian cancer syndrome (HOCS) in Shandong province, East China.
      METHODS: The present retrospective study assessed the clinicopathologic
      characteristics and prognosis among patients with HOCS treated at Shandong Cancer
      Hospital, China, between January 1, 2008, and January 31, 2016. Data from women
      with primary ovarian cancer who met HOCS diagnostic criteria (genetic-disease
      group) were compared with data from a control group of 100 women with sporadic
      ovarian cancer (sporadic-disease group) identified using simple random sampling.
      RESULTS: Among 1247 records of primary ovarian cancer during the study period, 96
      (7.7%) women from 77 pedigrees had HOCS (genetic-disease group), and 65 of these
      pedigrees had sufficient data available for inclusion. In the genetic-disease
      group, 55 (85%) and 10 (15%) women inherited the disease through the maternal and
      paternal lines, respectively. Age of onset was earlier in the genetic-disease
      group compared with the sporadic-disease group (P=0.016), the proportion of
      mucinous adenocarcinoma was lower in the genetic-disease group (P=0.006), and the
      genetic-disease group had higher 3-year (P=0.036) and 5-year (P=0.035) survival
      rates. CONCLUSION: HOCS exhibited maternal lineage primarily, and featured an
      early age of onset, advanced disease (stage III), serous adenocarcinoma, and a
      better prognosis after comprehensive treatment (including surgery, chemotherapy,
      and occasionally radiotherapy) relative to sporadic ovarian cancer.

PMID- 29359326
TI  - Phenotypic integration of the cervical vertebrae in the Hominoidea (Primates).
AB  - Phenotypic integration and modularity represent important factors influencing
      evolutionary change. The mammalian cervical vertebral column is particularly
      interesting in regards to integration and modularity because it is highly
      constrained to seven elements, despite widely variable morphology. Previous
      research has found a common pattern of integration among quadrupedal mammals, but
      integration patterns also evolve in response to locomotor selective pressures
      like those associated with hominin bipedalism. Here, I test patterns of
      covariation in the cervical vertebrae of three hominoid primates (Hylobates, Pan,
      Homo) who engage in upright postures and locomotion. Patterns of integration in
      the hominoid cervical vertebrae correspond generally to those previously found in
      other mammals, suggesting that integration in this region is highly conserved,
      even among taxa that engage in novel positional behaviors. These integration
      patterns reflect underlying developmental as well as functional modules. The
      strong integration between vertebrae suggests that the functional morphology of
      the cervical vertebral column should be considered as a whole, rather than in
      individual vertebrae. Taxa that display highly derived morphologies in the
      cervical vertebrae are likely exploiting these integration patterns, rather than
      reorganizing them. Future work on vertebrates without cervical vertebral number
      constraints will further clarify the evolution of integration in this region.

PMID- 29359325
TI  - Stress reactions following acute situations involving moral challenges among
      health care professionals.
AB  - : Many health care professionals have to make morally difficult decisions during
      acute, stressful situations. The aim was to explore the applicability of an
      existing qualitatively developed model of individual reactions among professional
      first responders following such situations using a quantitative approach.
      According to the model, the interaction of antecedent individual and contextual
      characteristics affect the immediate emotional reactions to acute, stressful
      events involving a moral dilemma. Continuous coping efforts and the quality of
      social support will also affect the long-term positive and negative reactions to
      the event. The participants (n = 204, about 50% response rate) represented three
      Swedish health care professions stationed at a university hospital and a regional
      hospital: Physicians (n = 50), nurses (n = 94) and "others" (n =60, mainly social
      welfare officers and assistant nurses). Except for the personality dimension
      emotional stability which was measured using an established instrument, all
      measurement scales were operationalizations of codes and categories from the
      qualitative study (ten scales altogether). Four multiple regression analyses were
      performed with long-term positive and negative reactions in everyday acute and
      morally extremely taxing situations respectively as dependent variables. The
      outcome showed that long-term positive reactions covaried with much use of the
      coping strategies Emotional distancing and Constructive emotional confrontation
      and a perception of a well-functioning Formal social support. Regarding long-term
      negative reactions, higher age and little use of Emotional distancing accounted
      for much of the variance. Immediate emotional reactions also contributed
      significantly. CONCLUSION: the results largely supported the model concepts and
      their assumed relationships.

PMID- 29359327
TI  - A rare cause of blanching red legs: cutaneous collagenous vasculopathy.

PMID- 29359329
TI  - Creutzfeldt-Jakob disease and blood transfusion safety.
AB  - Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal
      neurologic diseases affecting mammals. Human disease forms include sporadic,
      familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD)
      has been recognized for near on 100 years, variant CJD (vCJD) was first reported
      in 1996 and is the result of food-borne transmission of the prion of bovine
      spongiform encephalopathy (BSE, 'mad cow disease'). Currently, 230 vCJD cases
      have been reported in 12 countries, the majority in the UK (178) and France (27).
      Animal studies demonstrated highly efficient transmission of natural scrapie and
      experimental BSE by blood transfusion and fuelled concern that sCJD was
      potentially transfusion transmissible. No such case has been recorded and case
      control evaluations and lookback studies indicate that, if transfusion
      transmission occurs at all, it is very rare. In contrast, four cases of apparent
      transfusion transmission of vCJD infectivity have been identified in the UK. Risk
      minimization strategies in response to the threat of vCJD include leucodepletion,
      geographically based donor deferrals and deferral of transfusion recipients. A
      sensitive and specific, high-throughput screening test would provide a potential
      path to mitigation but despite substantial effort no such test has yet appeared.
      The initial outbreak of vCJD appears to be over, but concern remains about
      subsequent waves of disease among those already infected. There is considerable
      uncertainty about the size of the infected population, and there will be at least
      a perception of some continuing risk to blood safety. Accordingly, at least some
      precautionary measures will remain in place and continued surveillance is
      necessary.

PMID- 29359330
TI  - Social dominance orientation moderates the effectiveness of mindset messages.
AB  - In this work, we examine whether differences in social dominance orientation
      (SDO) moderate the effectiveness of mindsets of intelligence messages. We suggest
      that SDO is a foundational ideological belief system, on which individuals vary,
      that maintains the desire to endorse fixed beliefs about the nature of human
      intelligence. Thus, attempts to change individuals' mindsets should be met with
      resistance from those who strongly endorse the social dominance ideology -
      individuals high on SDO. In contrast, individuals low on SDO are less likely to
      use mindsets of intelligence to justify an ideological belief system, and thus,
      mindset manipulations should be effective for them. We test these predictions
      across three experimental studies (NStudy1  = 271, NStudy2  = 207, NStudy3  =
      313). Across the studies, we find that individuals who are high, relative to low,
      on SDO have more fixed beliefs about the nature of intelligence and show smaller
      effects of manipulations of mindsets. However, when comparing to a control
      condition, there was no evidence that high-SDO participants resisted the growth
      message that contradicts their ideology more than the fixed one that supports it;
      additionally, low-SDO participants showed heightened responsiveness to a fixed
      message. We discuss implications for theoretical advances in our understanding of
      mindsets.

PMID- 29359328
TI  - Galectin-3 is an amplifier of the interleukin-1beta-mediated inflammatory
      response in corneal keratinocytes.
AB  - Interleukin-1beta (IL-1beta) is a potent mediator of innate immunity commonly up
      regulated in a broad spectrum of inflammatory diseases. When bound to its cell
      surface receptor, IL-1beta initiates a signalling cascade that cooperatively
      induces the expression of canonical IL-1 target genes such as IL-8 and IL-6.
      Here, we present galectin-3 as a novel regulator of IL-1beta responses in corneal
      keratinocytes. Using the SNAP-tag system and digitonin semi-permeabilization, we
      show that recombinant exogenous galectin-3 binds to the plasma membrane of
      keratinocytes and is internalized into cytoplasmic compartments. We find that
      exogenous galectin-3, but not a dominant negative inhibitor of galectin-3
      polymerization lacking the N-terminal domain, exacerbates the response to IL
      1beta by stimulating the secretion of inflammatory cytokines. The activity of
      galectin-3 could be reduced by a novel d-galactopyranoside derivative targeting
      the conserved galactoside-binding site of galectins and did not involve
      interaction with IL-1 receptor 1 or the induction of endogenous IL-1beta.
      Consistent with these observations, we demonstrate that small interfering RNA
      mediated suppression of endogenous galectin-3 expression is sufficient to impair
      the IL-1beta-induced secretion of IL-8 and IL-6 in a p38 mitogen-activated
      protein kinase-independent manner. Collectively, our findings provide a novel
      role for galectin-3 as an amplifier of IL-1beta responses during epithelial
      inflammation through an as yet unidentified mechanism.

PMID- 29359331
TI  - Presentation, course, and outcome of postneonatal presentations of vein of Galen
      malformation: a large, single-institution case series.
AB  - AIM: To describe presentation, clinical course, and outcome in postneonatal
      presentations of vein of Galen malformation (VGM). METHOD: Children older than 28
      days presenting with VGM (from 2006-2016) were included. Notes/scans were
      reviewed. Outcome was dichotomized into 'good' or 'poor' using the Recovery and
      Recurrence Questionnaire. Logistic regression was performed to explore
      relationships between clinico-radiological features and outcome. RESULTS: Thirty
      one children (18 males, 13 females) were included, presenting at a median age of
      9.6 months (range 1.2mo-11y 7mo), most commonly with macrocrania (n=24) and
      prominent facial veins (n=9). Seven had evidence of cardiac failure. VGM
      morphology was choroidal in 19. Hydrocephalus (n=24) and loss of white matter
      volume (n=15) were the most common imaging abnormalities. Twenty-nine patients
      underwent glue embolization (median two per child). Angiographic shunt closure
      was achieved in 21 out of 28 survivors. Three children died of intracranial
      haemorrhage (1y, 6y, and 30d after embolization). Ten patients underwent
      neurosurgical procedures; to treat haemorrhage in four, and hydrocephalus in the
      rest. Outcome was categorized as good in 20 out of 28 survivors, but this was not
      predictable on the basis of the variables listed above. INTERPRETATION:
      Postneonatally presenting VGM has distinctive clinico-radiological features,
      attributable to venous hypertension. Endovascular treatment is associated with
      good outcomes, but more specific prognostic prediction was not possible within
      this cohort. WHAT THIS PAPER ADDS: Clinical and radiological features in older
      children with vein of Galen malformation relate to venous hypertension. Outcome
      is good in most cases with endovascular therapy. Mortality is low but is related
      to intracranial haemorrhage.

PMID- 29359332
TI  - Investigation of antibody to severe fever with thrombocytopenia syndrome virus
      (SFTSV) in blood samples donated in a SFTS-endemic area in Japan.
AB  - The risk of transfusion-transmitted infection (TTI) for severe fever with
      thrombocytopenia syndrome virus (SFTSV) is a concern because person-to-person
      transmission resulting from contact with SFTSV-contaminated blood has been
      reported. To obtain information regarding the risk of TTI-SFTSV, antibody testing
      was performed for blood samples donated in an severe fever with thrombocytopenia
      syndrome-endemic area in Japan. No antibody-positive samples were detected among
      3990 samples. This finding suggested that there were few cases of SFTSV infection
      among donors and that the risk of TTI-SFTSV was also estimated low in Japan.

PMID- 29359333
TI  - Divergence in pollen performance between Clarkia sister species with contrasting
      mating systems supports predictions of sexual selection.
AB  - Animal taxa that differ in the intensity of sperm competition often differ in
      sperm production or swimming speed, arguably due to sexual selection on
      postcopulatory male traits affecting siring success. In plants, closely related
      self- and cross-pollinated taxa similarly differ in the opportunity for sexual
      selection among male gametophytes after pollination, so traits such as the
      proportion of pollen on the stigma that rapidly enters the style and mean pollen
      tube growth rate (PTGR) are predicted to diverge between them. To date, no
      studies have tested this prediction in multiple plant populations under uniform
      conditions. We tested for differences in pollen performance in greenhouse-raised
      populations of two Clarkia sister species: the predominantly outcrossing C.
      unguiculata and the facultatively self-pollinating C. exilis. Within populations
      of each taxon, groups of individuals were reciprocally pollinated (n = 1153
      pollinations) and their styles examined four hours later. We tested for the
      effects of species, population, pollen type (self vs. outcross), the number of
      competing pollen grains, and temperature on pollen performance. Clarkia
      unguiculata exhibited higher mean PTGR than C. exilis; pollen type had no effect
      on performance in either taxon. The difference between these species in PTGR is
      consistent with predictions of sexual selection theory.

PMID- 29359334
TI  - Methazolamide-induced toxic epidermal necrolysis in a man carrying HLA-B*59:01:
      successful treatment with infliximab and glucocorticoid.

PMID- 29359335
TI  - Targeted recruitment of male donors for allogeneic haematopoietic cell
      transplantation: A review of the evidence.
AB  - Many patients in need of a haematopoietic cell transplant cannot find a suitable
      HLA-compatible donor within their families and rely on volunteers who have
      registered as haematopoietic stem cell donors with a stem cell donor registry.
      Transplant physicians mostly prefer male donors for their patients when multiple
      donor options exist, and organizations recruiting donors are actively targeting
      males in their recruitment efforts. However, significant recruitment of female
      donors continues worldwide and appears to be increasing. In this review, the
      evidence underlying transplant physician preference for male donor selection is
      summarized. The review will inform donor recruitment organizations contemplating
      a change in strategy to target potential male registrants and will equip donor
      recruitment staff and volunteers with a resource to better understand their
      recruitment efforts.

PMID- 29359336
TI  - Cutaneous eruptions by new therapies against hepatitis C virus infection. Not as
      common as we presumed.

PMID- 29359337
TI  - Nursing qualification and workforce for the Association of Southeast Asian
      Nations Economic Community.
AB  - International nurse migration among Association of Southeast Asian Nations
      (ASEAN) countries has the potential to increase the effectiveness of health
      services and access for the ASEAN Economic Community. Providing equivalent
      nursing qualifications and licensure standards and increasing the availability of
      the nursing workforce has become a challenge for ASEAN members. The purpose of
      this study is: 1) to comparatively analyze information on nursing licensing
      examinations (NLE) across ASEAN countries; and 2) to present information on the
      human resources required for a successful nursing workforce. This study reviews
      all documents published on the subject within the ASEAN Economic Community. NLE
      systems exist in all ASEAN Member States (AMSs)s except Brunei, Vietnam, and Lao
      PDR. Nursing education systems also vary across ASEAN countries. Language as a
      means of general communication and nursing examinations also differs. The
      availability of a qualified health workforce at the regional level is above the
      threshold in some areas. However, at the national level, Indonesia, Myanmar,
      Cambodia, and Lao PDR fall below the threshold. Professional licensure
      requirements differ among ASEAN nurses as a part of the process to become a
      qualified nurse in host and source countries. Mutual Recognition Agreements on
      nursing services should address the differences in NLE requirements as well as
      the availability of nurses.

PMID- 29359338
TI  - PI3K/AKT/JNK/p38 signalling pathway-mediated neural apoptosis in the prefrontal
      cortex of mice is involved in the antidepressant-like effect of pioglitazone.
AB  - Numerous studies have reported that inflammation is involved in the
      pathophysiology of depression. Pioglitazone, a PPAR-gamma agonist, has potential
      anti-inflammatory and antidepressive effects. However, the underlying molecular
      mechanisms of the antidepressant-like effect of pioglitazone on an inflammation
      related mouse model of depression remain to be fully elucidated. Herein, we aimed
      to explore the effects of pioglitazone on depressive-like behaviours of mice
      exposed to lipopolysaccharides (LPS), and elucidate the underlying mechanisms. We
      assessed behaviour changes of mice pretreated with pioglitazone exposed to LPS.
      Additionally, neural apoptosis, and the expression of apoptosis-related (cleaved
      caspase-3, Bax, Bcl-2, cyt c) and signalling proteins (AKT, JNK, p38) were
      assessed in the prefrontal cortex (PFC) of these mice. Furthermore, we assessed
      the influence of anisomycin, a JNK/p38 agonist, and LY294002, a PI3K/AKT
      inhibitor, on the antidepressant-like effect of pioglitazone in mice. We show
      that pioglitazone pretreatment (20 mg/kg, intragastrically) attenuated LPS
      induced (10 ng/MUL per site) depressive-like behaviours. GW9662, a PPAR-gamma
      antagonist, significantly blocked the antidepressant-like effect of pioglitazone.
      Furthermore, at the molecular level, pioglitazone significantly reversed, via
      PPAR-gamma-dependent increase in neural apoptosis in the PFC of mice, accompanied
      by upregulation of the PI3K/AKT pathway and down-regulation of the JNK/p38
      pathway. Moreover, both anisomycin and LY294002 abrogated the antidepressant-like
      effect of pioglitazone.; In conclusion, our results showed that PI3K/AKT/JNK/p38
      signalling pathway-mediated neural apoptosis in the PFC of mice may be involved
      in the antidepressant-like effect of pioglitazone. This provides novel insights
      into and therapeutic targets for inflammation-related depression.

PMID- 29359339
TI  - Adapting the vertical position of implants with a conical connection in relation
      to soft tissue thickness prevents early implant surface exposure: A 2-year
      prospective intra-subject comparison.
AB  - AIM: To evaluate the effect of soft tissue thickness on bone remodelling and to
      investigate whether implant surface exposure can be avoided by adapting the
      vertical implant position in relation to the soft tissue thickness. MATERIALS AND
      METHODS: Twenty-five patients received two non-splinted implants supporting an
      overdenture in the mandible. Soft tissue thickness was measured using bone
      sounding and ultrasonically. One implant was installed equicrestally (control),
      and the vertical position of the second implant was adapted to the site-specific
      soft tissue thickness (test). Crestal bone levels were determined on digital peri
      apical radiographs and compared with baseline (implant placement). RESULTS:
      Twenty-five patients were consecutively treated. No implants failed during the
      follow-up. A significant correlation was observed between soft tissue thickness
      and bone level alterations after 6 months (ultrasound ICC = 0.610; bone sounding
      ICC = 0.641) with inferior bone levels for equicrestal implants when thin tissues
      are present. Subcrestal implants showed significantly better bone levels after 6
      month (n = 24, 0.04 mm versus 0.72 mm; p < .001), 1-year (n = 24, 0.03 mm versus
      0.77 mm; p < .001) and 2-year follow-up (n = 24, 0.04 mm versus 0.73 mm; p <
      .001). CONCLUSION: Initial bone remodelling was affected by soft tissue
      thickness. Anticipating biologic width re-establishment by adapting the vertical
      position of the implant seemed highly successful to avoid implant surface
      exposure.

PMID- 29359340
TI  - Review: Mechanistic target of rapamycin (mTOR) pathway, focal cortical dysplasia
      and epilepsy.
AB  - Over the last decade, there has been increasing evidence that hyperactivation of
      the mechanistic target of rapamycin (mTOR) pathway is a hallmark of malformations
      of cortical development such as focal cortical dysplasia (FCD) or
      hemimegalencephaly. The mTOR pathway governs protein and lipid synthesis, cell
      growth and proliferation as well as metabolism and autophagy. The molecular
      genetic aetiology of mTOR hyperactivation has only been recently clarified. This
      article will review the current and still evolving genetic advances in the
      elucidation of the molecular basis of FCD. Activating somatic mutations in the
      MTOR gene are to date the most frequent mutations found in FCD brain specimens.

PMID- 29359341
TI  - Systematic review with meta-analysis: de novo non-alcoholic fatty liver disease
      in liver-transplanted patients.
AB  - BACKGROUND: De novo non-alcoholic fatty liver disease (NAFLD) in liver
      transplanted patients for cirrhosis not due to non-alcoholic steatohepatitis
      (NASH) is becoming a growing phenomenon. AIMS: We performed a systematic review
      and evaluated the prevalence of this event and possible associated factors.
      METHODS: A literature search in medical databases (PubMed, MEDLINE/OVIDSP,
      Science Direct and EMBASE) was performed in March 2017. Relevant publications
      were identified in most important databases. We estimated the pooled prevalence
      of NAFLD and NASH in patients with liver transplant. The data have been expressed
      as proportions/percentages, and 95% confidence intervals (CI) were calculated,
      using the inverse variance method. Odd ratios (OR) and 95% confidence intervals
      (95% CI) were estimated. RESULTS: Twelve studies were selected, enrolling 2166
      subjects overall undergoing post-liver transplant biopsy. The pooled weighted
      prevalence of de novo NAFLD was 26% (95% CI 20%-31%). The pooled weighted
      prevalence of NASH was 2% (95% CI 0%-3%). The highest prevalences of de novo
      NAFLD were found for patients transplanted for alcoholic cirrhosis (37%) and
      cryptogenic cirrhosis (35%) and for patients taking tacrolimus (26%). Tacrolimus
      showed a risk of NAFLD similar to ciclosporin (OR = 1.02, 95% CI 0.3-3.51).
      CONCLUSIONS: Patients undergoing liver transplant are more prone to experience
      diabetes, hypertension or dyslipidaemia, and NAFLD may be an important element in
      this context. In this study, we show how the prevalence of NASH tends to remain
      significant and similar to the general population. Moreover, this study suggests
      a possible association with specific transplant indications. Further studies are
      required to confirm these findings.

PMID- 29359342
TI  - Serum proteomic pattern in female stress urinary incontinence.
AB  - The pathophysiology of Stress Urinary Incontinence (SUI) is poorly understood.
      The aim of this study was to identify the serum proteomic profile in patients
      with SUI and to replicate findings from a preceding study in which a significant
      difference in the urinary proteome was identified. Serum samples were collected
      from 38 patients (19 SUI; 19 matched, continent controls). Sample preparation
      included serum albumin depletion, in-solution enzymatic digestion of proteins
      applying a combination of Gluc-C and trypsin and peptide separation using nano
      High Performance Liquid Chromatography. Label-free quantitation of peptides and
      proteins was performed after triplicate measurements using quadrupole time-of
      flight mass spectrometry. Peptide identification was achieved by searching the
      Human SwissProt Database using Mascot and X!Tandem. Main outcome measure was the
      relative abundance of each detected protein in serum. Of 7012 identified
      proteins, 33 proteins were induced (detected in SUI, not in controls) and five
      proteins were depleted (detected in controls, not in SUI). All depleted proteins
      play a role in immune/DNA damage response. Induced proteins are involved in
      inflammatory response, response to cellular stress, coagulation and cytoskeleton
      stability/ motility. Plasma serine protease inhibitor (SERPINA5) was found
      induced and previously also showed a higher abundance in urine samples of SUI
      patients. Data are available via ProteomeXchange with identifier PXD008553.

PMID- 29359343
TI  - Systematic review: psychosocial factors associated with pain in inflammatory
      bowel disease.
AB  - BACKGROUND: Pain is a frequently reported symptom of inflammatory bowel disease
      (IBD) experienced by patients in active disease and remission. Psychological
      factors play a significant role in pain, but have not been systematically
      reviewed in IBD. AIM: To review psychosocial factors associated with pain in
      adults diagnosed with IBD. METHODS: Electronic (PsycInfo, MEDLINE, EMBASE,
      Cochrane Library, CINAHL, Web of Science), and hand-searching were conducted
      February-May 2017. Two authors carried out screening and data extraction.
      RESULTS: Fifteen studies including 5539 IBD patients were identified. Emotional,
      cognitive-behavioural and personality factors were associated with IBD-pain.
      Depression and anxiety were the most commonly explored constructs, followed by
      perceived stress and pain catastrophising, all of which were positively
      associated with greater pain. Greater abdominal pain was associated with a
      concurrent mood disorder over fivefold (OR 5.76, 95% CI 1.39, 23.89). Coping
      strategies and pain fear avoidance correlated with pain levels. Perceived social
      support (r = .26) and internal locus of control (r = .33) correlated with less
      pain. Patients reporting pain in IBD remission more frequently had an existing
      diagnosis of a mood disorder, a chronic pain disorder and irritable bowel
      syndrome. Six studies controlled for disease activity, of which 4 found that
      psychosocial factors significantly predicted pain. The majority of studies (n =
      10) were of high quality. CONCLUSION: Psychosocial factors appear to play a
      significant role in IBD-pain. Further research is required to explore
      psychosocial constructs in relation to IBD-pain, with use of validated pain
      measures, large sample sizes and clearer characterisation of disease activity.

PMID- 29359344
TI  - Induction of abiotic stress tolerance in plants by endophytic microbes.
AB  - : Endophytes are micro-organisms including bacteria and fungi that survive within
      healthy plant tissues and promote plant growth under stress. This review focuses
      on the potential of endophytic microbes that induce abiotic stress tolerance in
      plants. How endophytes promote plant growth under stressful conditions, like
      drought and heat, high salinity and poor nutrient availability will be discussed.
      The molecular mechanisms for increasing stress tolerance in plants by endophytes
      include induction of plant stress genes as well as biomolecules like reactive
      oxygen species scavengers. This review may help in the development of
      biotechnological applications of endophytic microbes in plant growth promotion
      and crop improvement under abiotic stress conditions. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Increasing human populations demand more crop yield for food security
      while crop production is adversely affected by abiotic stresses like drought,
      salinity and high temperature. Development of stress tolerance in plants is a
      strategy to cope with the negative effects of adverse environmental conditions.
      Endophytes are well recognized for plant growth promotion and production of
      natural compounds. The property of endophytes to induce stress tolerance in
      plants can be applied to increase crop yields. With this review, we intend to
      promote application of endophytes in biotechnology and genetic engineering for
      the development of stress-tolerant plants.

PMID- 29359345
TI  - Simultaneous identification of the anaphylactoid components from traditional
      Chinese medicine injections using rat basophilic leukemia 2H3 and laboratory of
      allergic disease 2 dual-mixed/cell membrane chromatography model.
AB  - Traditional Chinese medicine (TCM) has been used for prevention and treatment of
      various diseases for many decades. TCM injection is a new dosage form, with
      incidence of anaphylactoid reactions increasing every year. In this study, the
      rat basophilic leukemia 2H3 (RBL-2H3) and laboratory of allergic disease 2 (LAD2)
      dual-mixed/CMC was established and was coupled with an HPLC-ESI-IT-TOF-MS system
      to identify the potential allergenic components in Haqing injection. Cinobufagin,
      piperine, osthole, praeruptorin A, and schizandrin A were screened from Haqing
      injection via this coupled system. Competitive binding assay showed piperine,
      praeruptorin A, and schizandrin A acting on MrgprX2 and cinobufagin and osthole
      act on the IgE receptor. The release of mediators of anaphylaxis results showed
      cinobufagin and osthole can cause anaphylactoid reactions by triggering the
      release of beta-hexosaminidase and histamine via IgE-R. Praeruptorin A and
      schizandrin A could promote the release of beta-hexosaminidase and histamine via
      MrgprX2 receptor. In summary, the dual-mixed/CMC model can significantly improve
      the efficiency of target component identification from a complex sample. When
      combined with competitive binding assay and validation of biological activities,
      this model enables accurate determination of the dual-target components, offering
      improved methods for quality control of TCM injections.

PMID- 29359346
TI  - Aesthetic reconstruction of retroauricular keloid: Creating a keystone flap from
      the mastoid-helix area.
AB  - Advances in aesthetic rhinoplasty using conchal cartilage grafts have led to a
      high occurrence of retroauricular keloids. The purpose of this study is to
      introduce our surgical experiences using a keystone flap in retroauricular
      keloids following conchal cartilage grafts. The present study is a retrospective
      review of patients with pathologically confirmed retroauricular keloids following
      conchal cartilage grafts. These cases were surgically excised and we covered the
      defect with a keystone flap followed by one-time steroid injection at
      postoperative day 14 and silicone gel sheeting application for 3 months.
      Treatment outcome was recorded as recurrence or non-recurrence. In all patients,
      a follow-up period of minimum 12 months was required. Of these patients, 90.0%
      had successful treatment of their auricular keloids, whereas 10.0% had
      recurrences. The postoperative course was uneventful. In conclusion, our
      aesthetic reconstruction using a keystone flap created from the mastoid-helix
      area is a useful treatment strategy in terms of retroauricular keloids following
      conchal cartilage grafts.

PMID- 29359347
TI  - Shuffling peptides to create T-cell epitopes: does the immune system play cards?
AB  - For a long time, immunologists have believed that classical CD4+ and CD8+ T cells
      recognize peptides (referred to as epitopes), derived from protein antigens
      presented by MHC/HLA class I or II. Over the past 10-15 years, it has become
      clear that epitopes recognized by CD8+, and more recently CD4+ T cells, can be
      formed by protein splicing. Here, we review the discovery of spliced epitopes
      recognized by tumor-specific human CD8+ T cells. We discuss how these epitopes
      are formed and some of the unusual variants that have been reported. Now, over a
      decade since the first report, evidence is emerging that spliced CD8+ T-cell
      epitopes are much more common, and potentially much more important, than
      previously imagined. Recent work has shown that epitopes recognized by CD4+ T
      cells can also be formed by protein splicing. We discuss the recent discovery of
      spliced CD4+ T-cell epitopes and their potential role as targets of autoimmune T
      cell responses. Finally, we highlight some of the new questions raised from our
      growing appreciation of T-cell epitopes formed by peptide splicing.

PMID- 29359349
TI  - miR-21a negatively modulates tumor suppressor genes PTEN and miR-200c and further
      promotes the transformation of M2 macrophages.
AB  - miR-21a is well-known to inhibit PTEN expression. We have previously shown that
      PTEN suppressed the transformation of M2 macrophages in the tumor
      microenvironment. Therefore, we hypothesized that miR-21a could influence M2
      macrophage transformation by regulating PTEN expression. In this study, we
      identified how miR-21a reduced the expression of both PTEN mRNA and protein in
      murine macrophage cell lines and primary macrophages. Moreover, opposite effects
      were identified upon the use of a miR-21a inhibitor. Using a cytokine array, we
      identified the cytokines closely associated with miR-21a-mediated macrophage
      transformation to the M2 phenotype. miR-21a mimics could also enhance the
      migratory ability of murine breast cancer 4T1 cells, the growth of breast cancer
      in vivo and CD206 intratumor expression. In addition, quantitative PCR (qPCR) and
      methylation-specific PCR analysis showed that miR-21a enhanced miR-200c
      methylation and then decreased miR-200c and PTEN expression. These effects could
      be reversed by treatment with 5'-Aza, a DNA-demethylating agent. MiR-200c was
      predicted to target the PTEN 3'UTR, but qPCR illustrated the miR-200c mimic that
      increased PTEN expression, and 5'-Aza could enhance its effect. The above results
      indicate that miR-21a negatively modulates two tumor suppressor genes, miR-200c
      and PTEN, thereby promoting M2 macrophage transformation. This demonstrates that
      miR-21a represents a novel target for improving the overall tumor
      microenvironment.

PMID- 29359350
TI  - Osteopontin contributes to effective neutrophil recruitment, IL-1beta production
      and apoptosis in Aspergillus fumigatus keratitis.
AB  - Fungal keratitis is a major cause of corneal ulcers, resulting in significant
      visual impairment and blindness. A phosphorylated glycoprotein secreted by
      immunocompetent cells, osteopontin (OPN) mediates cluster formation of the host
      fungal receptors and enhances the phagocytosis and clearance of pathogenic fungi.
      However, whether OPN production and function occurs in fungal keratitis is
      unknown. OPN expression in Aspergillus fumigatus keratitis patient corneas was
      assessed by quantitative polymerase chain reaction (qRT-PCR) and
      immunofluorescence. Human neutrophils, THP-1 macrophages and corneal epithelial
      cells (HCECs) stimulated with A. fumigatus were utilized for in vitro
      experiments. Mouse models of A. fumigatus keratitis were developed by
      intrastromal injection for in vivo experiments. Using siRNAs, neutralizing
      antibodies, recombinant proteins and inhibitors, the production and role of OPN
      in A. fumigatus infection was assessed by clinical evaluation, qRT-PCR,
      immunofluorescence, western blotting and bioluminescence image acquisition. We
      observed increased corneal OPN expression in A. fumigatus keratitis patients and
      mouse models compared to controls. OPN production in response to A. fumigatus
      infection was dependent on LOX-1 and Erk1/2. Compared to controls, OPN knockdown
      impaired proinflammatory cytokine IL-1beta production, which was dependent on 4E
      BP1. OPN knockdown decreased myeloperoxidase levels, and resulted in decreased
      neutrophil recruitment, higher fungal load and increased apoptosis in mouse A.
      fumigatus keratitis. Our results indicate that OPN is a critical component of the
      antifungal immune response and is essential for effective neutrophil recruitment,
      inflammatory cytokine production and apoptosis in A. fumigatus keratitis.

PMID- 29359351
TI  - Changes in retina and choroid after haemodialysis assessed using optical
      coherence tomography angiography.
AB  - BACKGROUND: Reports of choroidal and retinal changes before and after
      haemodialysis are few and have been controversial. Traditional imaging modalities
      are insufficient for quantitative assessment. This study aims to use optical
      coherence tomography angiography to monitor the short-term vascular density and
      thickness changes in retina and choroid before and after haemodialysis. METHODS:
      Seventy-seven eyes of 77 patients with end-stage kidney disease undergoing
      haemodialysis were included. Ophthalmologic examinations including optical
      coherence tomography angiography were performed one hour before and after
      haemodialysis. The vascular density of retina and choroid were measured and
      calculated by optical coherence tomography angiography. The retinal thickness and
      subfoveal choroidal thickness were measured manually using Image J software. The
      relationships between the changes in ocular and systemic parameters after
      haemodialysis were evaluated. RESULTS: The systolic blood pressure decreased from
      123.7 +/- 19.7 to 116.9 +/- 24.6 mmHg (p < 0.05) in all patients. The mean ocular
      perfusion pressure decreased significantly after haemodialysis in both diabetic
      and non-diabetic groups (p < 0.05). Mean retinal thickness decreased from 204.7
      +/- 22.4 MUm to 200.8 +/- 22.8 MUm (p < 0.05) after haemodialysis in all
      patients. The vascular density of outer retina was decreased from 38.8 +/- 5.5
      per cent to 37.5 +/- 3.4 per cent (p < 0.05) after haemodialysis in all patients.
      The changes in diastolic blood pressure, intraocular pressure, subfoveal
      choroidal thickness, vascular density of the superficial capillary plexus, deep
      capillary plexus and choriocapillaris were insignificant. There was no
      significant correlation between systolic blood pressure and the vascular density
      of the outer retina. CONCLUSION: In optical coherence tomography angiography, the
      retinal thickness became thinner and the vascular density in the outer retina
      decreased after haemodialysis in patients with end-stage kidney disease. The
      change of subfoveal choroidal thickness showed no significance after
      haemodialysis. The decreased volume in the retinal vascular bed and deficient
      choroidal autoregulatory control of ocular blood flow might be involved in the
      mechanism of these changes.

PMID- 29359352
TI  - Investigating the accuracy of FatNav-derived estimates of temporal B0 changes and
      their application to retrospective correction of high-resolution 3D GRE of the
      human brain at 7T.
AB  - PURPOSE: To investigate the precision of estimates of temporal variations of
      magnetic field achievable by double-echo fat image navigators (FatNavs), and
      their potential application to retrospective correction of 3-dimensional gradient
      echo-based sequences. METHODS: Both head motion and temporal changes of B0 were
      tracked using double-echo highly accelerated 3-dimensional FatNavs as navigators,
      allowing estimation of the temporal changes in low spatial-order field
      coefficients. The accuracy of the method was determined by direct comparison to
      controlled offsets in the linear imaging gradients. Double-echo FatNavs were also
      incorporated into a high-resolution, 3-dimensional gradient echo-based sequence
      to retrospectively correct for both motion and temporal changes in B0 during
      natural and deep breathing. The additional scan time was 5 min (a 40% increase).
      Correction was also investigated using only the first echo of the FatNav to
      explore the trade-off in accuracy versus scan time. RESULTS: Excellent accuracy
      (0.27 Hz, 1.57-2.75 Hz/m) was achieved for tracking field changes, and no
      significant bias could be observed. Artifacts in the 3-dimensional gradient echo
      based images induced by temporal field changes, if present, were effectively
      reduced using either the field estimates from the double echo or the first echo
      only from the FatNavs. CONCLUSION: The FatNavs were shown to be an excellent
      candidate for accurate, fast, and precise estimation of global field variations
      for the tested patterns of respiration. Future work will investigate ways to
      increase the temporal sampling to increase robustness to variations in breathing
      patterns. Magn Reson Med 80:585-597, 2018. (c) 2018 International Society for
      Magnetic Resonance in Medicine.

PMID- 29359353
TI  - MRI quantification of human fetal O2 delivery rate in the second and third
      trimesters of pregnancy.
AB  - PURPOSE: The purpose of this study was to estimate fetal O2 delivery rate in vivo
      across a range of gestational ages. Toward this, a calibration equation for T2 
      based oximetry was derived. METHODS: Umbilical cord blood of varying hematocrit
      (Hct) and oxygen saturation (HbO2 ) levels was prepared and T2 measured using a
      T2 -prepared balanced steady-state free-precession sequence at 1.5 T. The
      relationship between blood R2  = 1/T2 , HbO2 and Hct was established based on the
      model R2=(1-Hct)R2,plasma+Hct R2,RBC+k.Hct.(1-Hct).(1-HbO2)2. Experimental R2 ,
      HbO2 , and Hct levels were fit to the model-yielding values of k, R2,plasma, and
      R2,RBC (R2 of plasma and erythrocytes). Umbilical vein T2 measured in vivo was
      then converted to HbO2 , yielding-together with blood flow rate-the fetal O2
      delivery rate in 22 pregnancies (gestational age 30 +/- 3 weeks). RESULTS:
      Constants derived from the fit (R2  = 0.94) were k = 83.1 s-1 , R2,plasma=1.1  s
      1, and R2,RBC=12.9  s-1. The R2,RBC and k were found to be larger than those
      obtained for adult blood, likely the result of differences in dominant hemoglobin
      type. Data suggest that the use of adult blood calibration could entail errors up
      10% in fetal blood HbO2 . The average umbilical vein blood flow rate (89.5 +/-
      17.2 mL/min/kg), HbO2 (84 +/- 7%,), and fetal O2 delivery rate (15.1 +/- 3.8 mL
      O2 /min/kg) were independent of gestational age. The fetal O2 delivery rate
      agreed well with the results obtained with invasive methods at term. CONCLUSION:
      The present work describes strategies for measuring umbilical vein blood flow
      rate and HbO2 in vivo and estimates fetal O2 delivery rate noninvasively with
      quantitative MRI during the second and third trimesters of pregnancy. Magn Reson
      Med 80:1148-1157, 2018. (c) 2018 International Society for Magnetic Resonance in
      Medicine.

PMID- 29359354
TI  - PIKKing a way to regulate inflammation.
AB  - The phosphoinositide-3-kinase like kinases are a family of very large protein
      kinases. These PI3-kinase like kinase (PIKK) proteins have well-established roles
      in detection and repair of damage to the genome, regulation of the transcriptome
      and cellular metabolism. Recently there has emerged, evidence for links between
      these proteins and inflammation. While some of these links come from an increased
      understanding of the impacts of damage to the cell on inflammatory responses,
      others suggest that PIKK proteins also have direct roles in regulation of immune
      responses. Particularly evident is the link between DNA damage and innate immune
      response pathways. Here, we review recent findings on the PIKK family of proteins
      and how they impact on inflammation, particularly activation of the innate immune
      system.

PMID- 29359355
TI  - Influence of Carnicor, Venofer, and Sevelamer on the levels of genotoxic damage
      in end-stage renal disease patients.
AB  - End-stage renal disease (ESRD) patients present high levels of phosphorus and
      calcium products in serum, which contribute to the development of vascular
      calcification and cardiovascular disease, and to low iron stores and carnitine
      deficiency. For these reasons, ESRD patients are generally supplemented with
      different medicines. Some of the most common treatments include the use of
      Carnicor, Venofer, and Sevelamer drugs. Carnicor is used as a source of L
      carnitine, acting as antioxidant and neuroprotector. Venofer is used to reduce
      the deficit of iron. Sevelamer is used to treat hyperphosphatemia. To determine
      the potential harmful genotoxic effects of these drugs, a group of 214 patients
      included in a hemodialysis program with different intakes of Carnicor, Venofer,
      and Sevelamer were evaluated. The levels of basal and oxidative DNA damage, as
      well as chromosomal damage, were measured in all individuals using the comet and
      the micronucleus assays, respectively. Our results indicate that Carnicor
      administration was associated with low but significant increases in the frequency
      of basal DNA damage and micronuclei. Environ. Mol. Mutagen. 59:302-311, 2018. (c)
      2018 Wiley Periodicals, Inc.

PMID- 29359357
TI  - Letter in response to "Rethinking status dystonicus - A welcome start to a
      challenging problem".

PMID- 29359356
TI  - The value of glycated albumin for the prediction of graft outcome in the non
      human primate porcine islet transplantation model.
AB  - BACKGROUND: The development of a precise and easy-to-use tool for monitoring
      islet graft function is important in clarifying the causes of graft loss,
      identifying appropriate therapy, and ensuring graft survival in the nonhuman
      primate (NHP) model of porcine islet transplantation (PITx). Glycated albumin
      (GA) is an indicator of intermediate-term changes in blood glucose control and is
      useful in clinical diabetes management. The validity of GA for monitoring graft
      function in NHP recipients of PITx was evaluated using a retrospective analysis
      of cohort samples. METHODS: Data from a total of 23 PITxs performed in 20
      recipients (3 were retransplanted) were included in this study. Islet clusters
      purified from adult wild-type pigs were transplanted via the intraportal route
      into streptozotocin-induced diabetic rhesus monkeys with immune suppression.
      Blood samples were obtained once per week from the recipients until they lost
      insulin-independence. Blood samples were also obtained from 69 non-diabetic
      monkeys that served as a control group. The levels of GA and albumin in stored
      plasma aliquots were measured using each enzymatic method, and the GA result was
      expressed as the percentage of GA level to the total albumin level. RESULTS: The
      median level of GA in the recipients on the day of PITx (median 18.6%, 95%
      confidence interval [CI] 16.7%-20.4%) was significantly higher than that of
      healthy controls (median 9.14%, 95% CI 9.0%-9.3%, P < .0001). However, the level
      decreased after PITx and remained low or increased depending on the extent of
      residual graft function. The GA level at a nadir (median 11.6%, 95% CI 10.8%
      13.0%) and the time to reach a nadir (median 43 days, 95% CI 21.7-69.3 days) both
      correlated with the duration of insulin-independence (rho [rho] = -.605, P =
      .0028 and rho = .662, P = .0008, respectively). The GA level strongly correlated
      with KG , the glucose disappearance rate during intravenous glucose tolerance
      testing (rho = -.76, P < .0001). At post-transplant week (PTW) 3 and at PTW 4,
      the GA levels in recipients with long-term insulin-independence (>90 days) were
      significantly lower than those with short-term insulin-independence, which
      revealed the excellent performance for the prediction of long-term insulin
      independence that is comparable to that of porcine C-peptide (historic data).
      CONCLUSIONS: As a surrogate indicator for graft function, serial measurement of
      GA may provide Supporting Information to that obtained from conventional
      monitoring techniques of graft function for assessing porcine islet grafts in NHP
      models.

PMID- 29359358
TI  - Cytoplasmic glutamine synthetase gene expression regulates larval development in
      Bactrocera dorsalis (Hendel).
AB  - In insects, glutamine synthetase (GS), a key enzyme in the synthesis of
      glutamine, has been reported to be associated with embryonic development, heat
      shock response, and fecundity regulation. However, little is known about the
      influence of GS on postembryonic development. In this study, we demonstrate that
      blocking the activity of GS in the oriental fruit fly (Bactrocera dorsalis) with
      use of a GS-specific inhibitor (L-methionine S-sulfoximine), led to a significant
      delay in larval development, pupal weight loss, and inhibition of pupation. We
      further identify cloned and characterized two GS genes (BdGS-c and BdGS-m) from
      B. dorsalis. The two GS genes identified in B. dorsalis were predicted to be
      located in the cytosol (BdGS-c) and mitochondria (BdGS-m), and homology analysis
      indicated that both genes were similar to homologs from other Dipterans, such as
      Drosophila melanogaster and Aedes aegypti. BdGS-c was highly expressed in the
      larval stages, suggesting that cytosolic GS plays a predominant role in larval
      development. Furthermore, RNA interference experiments against BdGS-c, to
      specifically decrease the expression of cytosolic GS, resulted in delay in larval
      development as well as pupal weight loss. This study presents the prominent role
      played by BdGS-c in regulating larval development and suggests that the observed
      effect could have been modulated through ecdysteroid synthesis, agreeing with the
      reduced expression of the halloween gene spook. Also, the direct effects of BdGS
      c silencing on B. dorsalis, such as larval lethality, delayed pupation, and late
      emergence, can be further exploited as novel insecticide target in the context of
      pest management.

PMID- 29359359
TI  - Does size matter?

PMID- 29359360
TI  - Binaural frequency selectivity in humans.
AB  - Several behavioural studies in humans have shown that listening to sounds with
      two ears that is binaural hearing, provides the human auditory system with extra
      information on the sound source that is not available when sounds are only
      perceived through one ear that is monaurally. Binaural processing involves the
      analysis of phase and level differences between the two ear signals. As monaural
      cochlea processing (in each ear) precedes the neural stages responsible for
      binaural processing properties it is reasonable to assume that properties of the
      cochlea may also be observed in binaural processing. A main characteristic of
      cochlea processing is its frequency selectivity. In psychoacoustics, there is an
      ongoing discussion on the frequency selectivity of the binaural auditory system.
      While some psychoacoustic experiments seem to indicate poorer frequency
      selectivity of the binaural system than that of the monaural processing others
      seem to indicate the same frequency selectivity for monaural and binaural
      processing. This study provides an overview of these seemingly controversial
      results and the different explanations that were provided to account for the
      different results.

PMID- 29359361
TI  - Direct-acting antiviral treatment of chronic HCV-infected patients on opioid
      substitution therapy: Still a concern in clinical practice?
AB  - BACKGROUND AND AIMS: There is limited real-world information on the effectiveness
      of antiviral treatment of chronic hepatitis C virus (HCV) infection with direct
      acting antivirals (DAA) in people on opioid substitution therapy (OST). This
      study compared sustained virological response (SVR) rates and proportion of lost
      to follow-up (LTFU) between OST and non-OST patients in the German Hepatitis C
      Registry (DHC-R). DESIGN: National multi-centre prospective real-world registry
      (German Hepatitis C-Registry, DHC-R). Non-OST patients comprised patients with
      former/current drug use (non-OST/DU) and patients never consuming drugs (non
      OST/NDU). SETTING: A total of 254 medical centres in Germany, including 123
      centres providing OST. PARTICIPANTS: A total of 7747 chronic HCV patients started
      DAA therapy (739 OST and 7008 non-OST; 1500 non-OST/DU; 5508 non-OST/NDU)
      patients. Five hundred and twenty-eight OST and 5582 non-OST patients had
      completed antiviral therapy and at least one follow-up documentation [intention
      to-treat (ITT) population]. MEASUREMENTS: Study outcomes were SVR, proportion of
      LTFU and safety of treatment. FINDINGS: SVR (ITT) was documented in 85% (450 of
      528) OST patients versus 86% (969 of 1126) in non-OST/DU (P = 0.651) and 92%
      (4113 of 4456) non-OST/NDU (P < 0.001) patients. Independent predictors for SVR
      (P < 0.01 in multivariate analysis) included HCV genotype non-3 [adjusted odds
      ratio (aOR) = 1.11; 95% confidence interval (CI) = 1.07-1.15], female sex (aOR =
      1.59; CI = 1.30-1.94), platelet counts >90 * 109/l (aOR = 1.51, CI = 1.14-2.01),
      cirrhosis (aOR = 0.77; CI = 0.62-0.96) and patient group (OST/DI (aOR = 0.58; CI
      = 0.42-0.78); non-OST/DU (OR: 0.63; CI = 0.50-0.78). In per-protocol analysis
      (PP), SVR rates were >= 94% in all patient groups. In OST the proportion of LTFU
      was higher (10.2%) than in non-OST/DU (8.5%) and non-OST/NDU (3.2%, P < 0.001)
      patients. Independent factors for LTFU (P < 0.01) were HCV genotype non-3 (aOR =
      0.92; CI = 0.88-0.96), female sex (aOR: 0.7; CI = 0.53-0.92), pre-treatment (aOR
      = 0.64; CI = 0.50-0.82), OST/DI (aOR = 3.35; CI = 2.35-4.78) and non-OST/DU (aOR
      = 2.38; CI = 1.80-3.14). CONCLUSIONS: In Germany, direct-acting antiviral
      treatment of former or current drug users with or without opioid substitution
      therapy can achieve equally high sustained virological response rates as in
      patients with no history of drug use.

PMID- 29359362
TI  - Cholinergic interneurons in the rat striatum modulate substitution of habits.
AB  - Behavioural flexibility is crucial for adaptive behaviour, and recent evidence
      suggests that cholinergic interneurons of the striatum play a distinct role.
      Previous studies of cholinergic function have focused on strategy switching by
      the dorsomedial or ventral striatum. We here investigated whether cholinergic
      interneurons in the dorsolateral striatum play a similar role at the level of
      switching of habitual responses. Because the dorsolateral striatum is
      particularly involved in habitual responding, we developed a habit substitution
      task that involved switching habitual lever-press responses to one side to
      another. We first measured the effect of cholinergic activation in the
      dorsolateral striatum on this task. Chemogenetic activation of cholinergic
      interneurons caused an increase in the response rate for the substituted response
      that was significantly greater than the increase normally seen in control
      animals. The increase was due to burst-like responses with shorter inter-press
      intervals. However, there was no effect on inhibiting the old habit, or on
      habitual responding that did not require a switch. There was also no effect on
      lever-press performance and its reversal before lever-press responses became
      habitual. Conversely, neurochemically specific ablation of cholinergic
      interneurons did not significantly change habitual responding or response
      substitution. Thus, activation -but not ablation -of cholinergic interneurons in
      the dorsolateral striatum modulates expression of a new habit when an old habit
      is replaced by a new one. Together with previous work, this suggests that
      striatal cholinergic interneurons facilitate behavioural flexibility in both
      dorsolateral striatum in addition to dorsomedial and ventral striatum.

PMID- 29359364
TI  - Correction to: 'The effects of cannabis intoxication on motor vehicle collision
      revisited and revised' (2016).

PMID- 29359363
TI  - Comparison of efficiency of in vitro cloned sheep embryo production by
      conventional somatic cell nuclear transfer and handmade cloning technique.
AB  - Conventional somatic cell nuclear transfer (SCNT) technique of in vitro
      production of cloned embryos involves use of costly and complicated
      micromanipulators. Handmade cloning (HMC) technique has been applied as efficient
      and cost-effective alternative in many livestock species. The aim of the present
      study was to compare the efficiency of in vitro production and in vitro
      development of cloned sheep embryos by the two techniques. Cloned embryos were
      produced by conventional SCNT using micromanipulator apparatus and by HMC
      technique. Enucleation efficiency and efficiency of fusion with somatic cell
      (nucleus donor) were compared. Cleavage percentage was observed on day 2 of in
      vitro culture (IVC), and morula and blastocyst percentages were calculated on day
      7 of IVC. Higher enucleation efficiency (96.98 +/- 1.01 vs. 93.62 +/- 1.03; p >
      .05) as well as fusion efficiency was obtained with HMC technique than with
      conventional SCNT (96.26 +/- 1.34 vs. 92.63 +/- 0.70, p < .05); 181 cloned sheep
      embryos were produced in vitro by conventional SCNT and 92 by HMC. Cleavage
      percentage observed on day 2 of in vitro culture was higher in HMC than SCNT
      (66.92 +/- 3.72 vs. 55.97 +/- 2.5, respectively, p < .05). Morula percentage
      obtained was higher in SCNT than HMC (44.12 +/- 2.93 vs. 30.43 +/- 6.79,
      respectively, p < .05), whereas blastocyst percentage obtained by HMC was higher
      (12.46 +/- 4.96) than SCNT (5.31 +/- 2.25; p > .05). It was inferred that HMC
      technique provides a cost-effective and efficient method of in vitro production
      of cloned sheep embryos with a comparatively simpler technique with a possibility
      of automation. Efficiency of cloned embryo production could be improved further
      by propagating and standardizing this technique.

PMID- 29359365
TI  - Dance on cortex: enhanced theta synchrony in experts when watching a dance piece.
AB  - When watching performing arts, a wide and complex network of brain processes
      emerge. These processes can be shaped by professional expertise. When compared to
      laymen, dancers have enhanced processes in observation of short dance movement
      and listening to music. But how do the cortical processes differ in musicians and
      dancers when watching an audio-visual dance performance? In our study, we
      presented the participants long excerpts from the contemporary dance choreography
      of Carmen. During multimodal movement of a dancer, theta phase synchrony over the
      fronto-central electrodes was stronger in dancers when compared to musicians and
      laymen. In addition, alpha synchrony was decreased in all groups during large
      rapid movement when compared to nearly motionless parts of the choreography. Our
      results suggest an enhanced cortical communication in dancers when watching dance
      and, further, that this enhancement is rather related to multimodal, cognitive
      and emotional processes than to simple observation of dance movement.

PMID- 29359366
TI  - Ultrasound-guided lumbar plexus block in children and adolescents using a
      transverse lumbar paravertebral sonogram: Initial experience.
AB  - BACKGROUND: The clinical reliability and reproducibility of ultrasound-guided
      lumbar plexus blocks is not established in pediatric populations. We present the
      results of a combined nerve stimulation ultrasound-guided lumbar plexus block
      using the vertebral body, transverse process, and psoas muscle as landmarks on a
      transverse lumbar paravertebral sonogram with mid-axillary transducer placement,
      "shamrock method," in children and adolescents. AIMS: Our primary objective was
      to determine the rate of achieving sensory changes in the lumbar plexus
      distribution. Secondary outcomes were performance time, reliability of echo
      landmarks, measures of patient comfort, and complications. METHODS: We reviewed
      prospectively collected quality assurance data and electronic medical records of
      21 patients having major orthopedic surgery with lumbar plexus block catheter for
      postoperative analgesia. RESULTS: Twenty-one patients were studied with mean age
      and weight (SD, range) of 13.6 years (3.8, 6-18) and 49.3 kg (18.6, 19.2-87.6).
      Surgical procedures included periacetabular osteotomy, pelvic osteotomy, and
      proximal femoral osteotomy. Mean volume of 0.5 mL/kg (0.05) 0.2% ropivacaine
      produced thermal sensory changes to femoral and lateral femoral cutaneous nerves
      in 20/21 (95% CI 0.76 to >0.99) and 19/21 (95% CI 0.70-0.99) patients.
      Identification of transverse process (TP), vertebral body (VB), and psoas muscle
      (PM): 21/21 (95% CI 0.86-1.0). Average block performance time was 9:08 minutes
      (2:09, 2-13). Average opioid consumption (SD) in operating room, postanesthesia
      care unit, 0-12 and 12-24-hour periods were 0.17 mg/kg (0.08), 0.08 mg/kg (0.06),
      0.06 mg/kg (0.06), and 0.06 mg/kg (0.05). Median pain score by severity category
      in postanesthesia care unit: (0-3) 66.7%, (4-6) 28.5%, (>7) 4.8%; 0-12 hours: (0
      3) 76.2%, (4-6) 19.0%, (>7) 4.8%; 12-24 hours: (0-3) 57.2%, (4-6) 42.8%, (>7) 0%.
      No complications were recorded. CONCLUSION: Ultrasound guidance using lateral
      imaging of transverse process, vertebral body, and psoas muscle allows
      practitioners to reach the nerves of the lumbar plexus and achieve sensory block
      in pediatric patients with a high success rate.

PMID- 29359368
TI  - B-Flow and B-Mode Ultrasound Imaging in Carotid Fibromuscular Dysplasia.
AB  - BACKGROUND AND PURPOSE: Previous ultrasound studies in fibromuscular dysplasia
      (FMD) have largely reported on color flow imaging, power Doppler, and Doppler
      flow augmentation. We here report on arterial wall imaging findings by B-flow and
      B-mode in patients with carotid FMD. METHODS: We retrospectively reviewed
      ultrasonographic findings in subjects with known or suspected FMD. All patients
      were evaluated with a standardized imaging protocol including Doppler, B-mode,
      and B-flow. Vessel wall abnormalities were classified as normal, luminal
      irregularities, or classical beading (fusiform dilatations). RESULTS: We
      identified 23 patients and 33 carotid arteries were found to be abnormal, of
      which 10 had classical beading and 23 showed endoluminal irregularities.
      Bilateral disease was present in 10/23 patients. In the classical beading cases,
      B-mode revealed isoechoic ridges, which protruded into the lumen, alternating
      with dilated arterial segments, which were also clearly demonstrated by B-flow
      imaging. In cases with endoluminal irregularities, B-mode and B-flow showed
      isoechoic subendothelial irregular thickening, which did not lead to a fusiform
      dilatory appearance of the artery. The average distal internal carotid artery
      peak systolic velocity of arteries with classical beading (123 +/- 29 cm/second)
      was significantly greater than that of arteries with mild irregularities (94 +/-
      34 cm/second) (P = .024). CONCLUSION: Morphological arterial wall changes of FMD
      were well depicted by careful B-flow and B-mode imaging of the distal internal
      carotid artery. We would like to emphasize the utility of B-flow and B-mode in
      the noninvasive evaluation of FMD.

PMID- 29359367
TI  - Truncating mutations of TP53AIP1 gene predispose to cutaneous melanoma.
AB  - Genetic predisposition to cutaneous malignant melanoma (CMM) involves highly
      penetrant predisposing genes and low and intermediate penetrant predisposing
      alleles. However, the missing heritability in (CMM) is still high. For such and
      in order to identify new genetic factors for CMM, we conducted an exome
      sequencing study in high-risk CMM patients. Two rounds of exome sequencing were
      successively performed in 33 and 27 high-risk patients. We focused on genes
      carrying rare nonsense, frameshift, and splice variants (allelic frequency <1%)
      that were present in both series of exomes. An extension study was then conducted
      in a large cohort (1 079 CMM patients and 1 230 Caucasian ethnically matched
      healthy controls), and the inactivating variants frequency was compared between
      groups using two-sided Fisher exact test. Two TP53AIP1 truncating mutations were
      identified in four patients: a frameshift c.63_64insG, p.Q22Afs*81 in two
      patients from the same family and in the proband of a second family; and a
      nonsense mutation c.95 C > A, p.Ser32Stop in a patient with multiple CMMs. In all
      patients, TP53AIP1 truncating variants were strongly associated with CMM risk
      (two-sided Fisher exact test = 0.004, OR = 3.3[1.3-8.5]). Additionally, we showed
      that TP53AIP1 mRNA was strongly down-regulated throughout different phases of
      melanoma progression. TP53AIP1 gene is a TP53 target which plays a key role by
      inducting apoptosis in response to UV-induced DNA damage. Constitutional
      mutations of TP53AIP1 had previously been involved in susceptibility to prostate
      cancer. Our results show that constitutional truncating TP53AIP1 mutations
      predispose to CMM in the French population. Replication studies in other
      populations should be performed.

PMID- 29359369
TI  - Using activity schedules to promote varied application use in children with
      autism.
AB  - We evaluated the effects of an activity schedule embedded within an iPad on
      varied play across applications. After establishing a pattern of repetitive
      gameplay, we taught three children with autism to follow the activity schedule
      using physical guidance. All participants increased their varied play to four
      applications per session and demonstrated independent and accurate activity
      schedule usage. The activity schedule was removed, and responding decreased to
      baseline levels, demonstrating the activity schedule's control over varied
      responding. The activity schedule was reintroduced and participant responding
      maintained when engaging with novel applications.

PMID- 29359370
TI  - Descriptive assessment of problem behavior during transitions of children with
      intellectual and developmental disabilities.
AB  - Transitions from one activity to another may evoke problem behavior from
      individuals with intellectual disabilities. One explanation for the occurrence of
      problem behavior could be the change in relative densities of reinforcement
      between the two activities. We conducted a descriptive assessment of problem
      behavior with four children during transitions to and from several different
      contexts. We observed that, in most cases, the probability of problem behavior
      was greater during a transition to an activity with a lower density of
      reinforcement than during a transition to an activity with a higher density of
      reinforcement. We discuss our findings in terms of problem behavior associated
      with transitions in activities with different reinforcer densities, as well as
      the possibility that the problem behavior may be associated with shifts in
      motivating operations.

PMID- 29359371
TI  - Evaluation of stimulus intensity fading on reduction of rapid eating in a child
      with autism.
AB  - This study assessed the effects of a vibrating pager on reduction of rapid
      eating. The study also evaluated two strategies for fading the pager, by
      intensity and by frequency. The pager was successful in decreasing the pace of
      eating to an appropriate level and the pager prompt was successfully faded.
      Fading by frequency was ineffective in maintaining an appropriate pace of eating
      while intensity fading was successful.

PMID- 29359372
TI  - Recurrent painful ophthalmoplegic neuropathy in a 12-year-old boy.

PMID- 29359373
TI  - Action competence: A concept analysis.
AB  - AIM: The aim of this article is to analyze the concept of action competence and
      comprise a definition of the concept suitable to apply to virtual simulation in
      nursing education. BACKGROUND: Virtual simulation has become an instructional
      method increasingly used in nursing education which creates a challenge for
      assessment of clinical competence. DESIGN: This concept analysis was performed
      using Walker and Avant's eight stages of concept analysis. DATA SOURCE: A
      literature search was conducted using search engines and included peer-reviewed
      articles from various disciplines. RESULTS: The concept analysis resulted in an
      operational definition of action competence that is useful in nursing education.
      CONCLUSION: The use of action competence during virtual simulation sessions
      provides a means for knowledge transfer, accountability of actions on the part of
      the students, self-awareness, and reflection. Through this process, students gain
      critical problem-solving skills that, through sustainability, can be applied to
      varying future patient scenarios. Action competence contains concrete components
      applicable to sustainability of knowledge gained by nursing students during
      virtual simulation.

PMID- 29359374
TI  - Value of clinical features to differentiate refractory epilepsy from mimics: a
      prospective longitudinal cohort study.
AB  - BACKGROUND AND PURPOSE: Misdiagnosis of refractory epilepsy (rE) is common and
      such patients experience a long diagnostic delay. Our aim was to identify key
      clinical/laboratory factors in order to obtain an alternative diagnosis in
      patients referred for rE. METHODS: Between January 2010 and December 2015, 125
      consecutive patients with a diagnosis of rE were prospectively enrolled. All
      patients underwent a comprehensive neurological, neuropsychiatric and
      cardiological evaluation, and had an observation time of at least 1 year after
      the study entry. RESULTS: Diagnosis of rE was confirmed in 104/125 (83.2%)
      patients (55 women, mean age 38.8 +/- 14.3 years). Thirteen/125 patients (10.4%,
      seven women, mean age 50.8 +/- 20.9) were diagnosed with syncope, which was
      cardiac/cardio inhibitory in 9/13 (69%). The remaining 8/125 patients (6.4%, six
      women, mean age 41.2 +/- 14.6 years) were diagnosed with psychogenic non
      epileptic seizures. Age at onset had a high accuracy in differentiating patients
      with syncope from others, with the best cut-off age at 35 years and above.
      Abnormal brain magnetic resonance imaging (MRI) had a significant yield of about
      70% in rE. A diagnostic model including age at onset and brain MRI was highly
      accurate in differentiating patients with syncope from others. In patients with
      cardiac/cardio inhibitory syncope, the point score of historical features was >=1
      and falsely favoured the diagnosis of epileptic seizures. CONCLUSIONS: This
      prospective cohort study identifies rE mimics who are at high risk of morbidity
      and mortality. rE starting in adulthood should raise a high suspicion of cardiac
      syncope. Brain MRI is accurate in differentiating rE from other conditions.

PMID- 29359375
TI  - A scalable multi-resolution spatio-temporal model for brain activation and
      connectivity in fMRI data.
AB  - Functional Magnetic Resonance Imaging (fMRI) is a primary modality for studying
      brain activity. Modeling spatial dependence of imaging data at different spatial
      scales is one of the main challenges of contemporary neuroimaging, and it could
      allow for accurate testing for significance in neural activity. The high
      dimensionality of this type of data (on the order of hundreds of thousands of
      voxels) poses serious modeling challenges and considerable computational
      constraints. For the sake of feasibility, standard models typically reduce
      dimensionality by modeling covariance among regions of interest (ROIs)-coarser or
      larger spatial units-rather than among voxels. However, ignoring spatial
      dependence at different scales could drastically reduce our ability to detect
      activation patterns in the brain and hence produce misleading results. We
      introduce a multi-resolution spatio-temporal model and a computationally
      efficient methodology to estimate cognitive control related activation and whole
      brain connectivity. The proposed model allows for testing voxel-specific
      activation while accounting for non-stationary local spatial dependence within
      anatomically defined ROIs, as well as regional dependence (between-ROIs). The
      model is used in a motor-task fMRI study to investigate brain activation and
      connectivity patterns aimed at identifying associations between these patterns
      and regaining motor functionality following a stroke.

PMID- 29359376
TI  - Penile injury incurred during judo.

PMID- 29359377
TI  - Successful management of obstetric disseminated intravascular coagulation using a
      portable fibrinogen-measuring device.
AB  - The importance of fibrinogen replacement therapy in obstetric disseminated
      intravascular coagulation is well recognized. However, fibrinogen measurement in
      conventional laboratories has been a time-consuming task. Recently, a Japanese
      manufacturer developed a portable device that enables immediate fibrinogen
      measurement at the point of care. This report describes a case in which this
      device was used for the successful management of obstetric disseminated
      intravascular coagulation.

PMID- 29359379
TI  - Disparate clinical findings in monochorionic twins with neonatal hemochromatosis.

PMID- 29359380
TI  - (NHC)NiH-Catalyzed Regiodivergent Cross-Hydroalkenylation of Vinyl Ethers with
      alpha-Olefins: Syntheses of 1,2- and 1,3-Disubstituted Allyl Ethers.
AB  - Cross-hydroalkenylation of a vinyl ether (1) with an alpha-olefin (2) was first
      achieved by a set of [NHC-Ni(allyl)]BArF (NHC=N-heterocyclic carbene) catalysts.
      Both 1,2- and 1,3-disubstituted allyl ethers were obtained, highly selectively,
      by using NHCs of different sizes. In contrast, the chemoselectivity (i.e., 1 as
      acceptor and 2 as donor) was controlled mostly by electronic effects through the
      catalyst-substrate interaction. Sterically bulkier alkenes (2) were used as
      preferred donors compared to smaller alkenes. This electronic effect also served
      as a basis for the first tail-to-head cross-hydroalkenylations of 1 with either a
      vinyl silane or boronic ester.

PMID- 29359378
TI  - Modern Electrochemical Aspects for the Synthesis of Value-Added Organic Products.
AB  - The use of electricity instead of stoichiometric amounts of oxidizers or reducing
      agents in synthesis is very appealing for economic and ecological reasons, and
      represents a major driving force for research efforts in this area. To use
      electron transfer at the electrode for a successful transformation in organic
      synthesis, the intermediate radical (cation/anion) has to be stabilized. Its
      combination with other approaches in organic chemistry or concepts of
      contemporary synthesis allows the establishment of powerful synthetic methods.
      The aim in the 21st Century will be to use as little fossil carbon as possible
      and, for this reason, the use of renewable sources is becoming increasingly
      important. The direct conversion of renewables, which have previously mainly been
      incinerated, is of increasing interest. This Review surveys many of the recent
      seminal important developments which will determine the future of this dynamic
      emerging field.

PMID- 29359381
TI  - Inappropriate medication use and polypharmacy in end-stage cancer patients: Isn't
      it the family doctor's role to de-prescribe much earlier?
AB  - BACKGROUND: Elderly patients are exposed to increased number of medications,
      often with no proof of a positive benefit/risk ratio. Unfortunately, this trend
      does not spare those with limited life expectancy, including end-stage cancer
      patients who require only palliative treatment. For many medications in this
      subpopulation, the risk of adverse drug events outweighs the possible benefits
      and yet, many are still poly-medicated during their last year of life. AIM: To
      describe the extent of polypharmacy among end-stage cancer patients, at the time
      of admission to homecare hospice. METHODS: A retrospective chart review of 202
      patients admitted to Homecare Hospice of the Israel Cancer Association and died
      before January 2015. RESULTS: Average lifespan from admission until death was
      39.2 +/- 5.4 days. 63% died within the first month, 89% within 3 months.
      Excluding oncological treatments, 181 (90%) and 46 (23%) patients were treated
      with >= 6 and >= 12 drugs for chronic diseases, respectively. Two months before
      death, 32 (16%) patients were treated with >= 3 blood pressure lowering drugs, 62
      (31%) with statins and 48 (23%) with aspirin. CONCLUSION: Though not
      representative of the whole end-stage cancer patient population, our study
      demonstrates that these patients are exposed to extensive polypharmacy. Most of
      these medications could have probably been safely de-prescribed much earlier in
      the course of the malignant disease. Considering the prolonged trust-based
      relationship with their patients, the family physicians are those who should be
      encouraged to implement the palliative approach and reduce polypharmacy much
      before reaching hospice settings.

PMID- 29359382
TI  - The moderating effect of social support on the relationship between physical
      health and suicidal thoughts among Chinese rural elderly: A nursing home sample.
AB  - Suicide rate is relatively high among Chinese rural elderly. While there has been
      some exciting work on reporting and preventing suicide among community-dwelling
      elderly, only a few published studies have addressed the issues of rural nursing
      homes in China. This study aimed to investigate the relationship among perceived
      social support, physical health, and suicidal thoughts of the elderly living in
      Chinese rural nursing homes. It also examined the moderating effects of social
      support on the path from physical health to suicidal thoughts of the rural
      institutional elderly in China. This study investigated 205 participants aged 60
      years and above in Chinese rural nursing homes. Participants' suicidal thoughts,
      perceived social support, and physical health were assessed. This study conducted
      descriptive analysis, Student's t-test, and Pearson's chi-square test to test how
      physical health and social support predicted suicidal thoughts, as well as the
      moderating effects of family's, friends', and others' social support on physical
      health and suicidal thoughts. Both physical health and perceived social support
      were significantly related to suicidal thoughts. Perceived social support from
      family, friends, and significant others moderated the relationship between
      physical health and suicidal thoughts. Findings of this study suggested that
      increasing social support and improving physical health would be effective in
      both suicide prevention and intervention for the residents in Chinese rural
      nursing homes.

PMID- 29359383
TI  - Phosphine-Catalyzed anti-Carboboration of Alkynoates with 9-BBN-Based 1,1
      Diborylalkanes: Synthesis and Use of Multisubstituted gamma-Borylallylboranes.
AB  - Trialkylphosphine organocatalysis has enabled the regioselective anti
      carboboration of alkynoates with 9-BBN-based 1,1-diborylalkanes to produce
      secondary allylboranes with beta-alkoxycarbonyl and gamma-boryl substituents. The
      utility of the densely functionalized allylboranes was demonstrated by the highly
      diastereoselective allylation of N-(trimethylsilyl)aldimines to produce
      homoallylamines containing tertiary allylborane and acrylate moieties.

PMID- 29359384
TI  - Formation of Acetylene in the Reaction of Methane with Iron Carbide Cluster
      Anions FeC3- under High-Temperature Conditions.
AB  - The underlying mechanism for non-oxidative methane aromatization remains
      controversial owing to the lack of experimental evidence for the formation of the
      first C-C bond. For the first time, the elementary reaction of methane with
      atomic clusters (FeC3- ) under high-temperature conditions to produce C-C
      coupling products has been characterized by mass spectrometry. With the elevation
      of temperature from 300 K to 610 K, the production of acetylene, the important
      intermediate proposed in a monofunctional mechanism of methane aromatization, was
      significantly enhanced, which can be well-rationalized by quantum chemistry
      calculations. This study narrows the gap between gas-phase and condensed-phase
      studies on methane conversion and suggests that the monofunctional mechanism
      probably operates in non-oxidative methane aromatization.

PMID- 29359385
TI  - Clinical study to evaluate the performance of a noninvasive focused ultrasound
      device for thigh fat and circumference reduction compared to control.
AB  - BACKGROUND AND OBJECTIVES: An FDA-cleared focused ultrasound device (UltraShape,
      Syneron Candela(r) , Yokneam, Israel) for noninvasive abdominal fat reduction
      produces localized mechanical cellular membrane disruption in adipocytes. This
      study seeks to determine the safety and efficacy of this device for use on the
      thighs. STUDY DESIGNS/MATERIALS AND METHODS: Fourteen women aged 33-60 were
      selected to receive 3 biweekly treatments to one thigh with the other thigh
      serving as an internal control. The subjects had a BMI range of 18-30 kg/m2 and a
      weight range of 54-83 kg. After the third treatment, patients were followed at 4,
      8, and 16 weeks. Fat thickness was measured by both caliper and ultrasound. In
      addition, thigh circumference and the patient's weight were measured. Pain,
      edema, erythema, and adverse events as well as investigator and patient overall
      satisfaction were recorded at all visits. RESULTS: In comparison with the
      control, there was a statistically significant average reduction in fat thickness
      measured by calipers at all time points with a 22.20% (P = .0165) improvement in
      16 weeks. By ultrasound, there was a 19.23% (4.03 mm P = .0051) reduction in fat
      thickness at 16 weeks with statistically significant improvement at the other
      follow-up visits. At 16 weeks, thigh circumference improved, on average, 2.8 cm
      (P = .0059) at the midline. 90.0% of the subjects were satisfied with the results
      at 16 weeks, and the investigator was 100% satisfied. No adverse events were
      reported; no edema was observed in any subject. All subjects experienced mild
      erythema. All reported zero pain on a 0-10 scale. CONCLUSION: Focused ultrasound
      is safe, effective, and well tolerated to improve the circumference and fat
      thickness of the thighs without significant side effects. There were no
      significant adverse events. Investigators and subjects were highly satisfied with
      the results.

PMID- 29359386
TI  - Home opioid use following cesarean delivery: How many opioid tablets should
      obstetricians prescribe?
AB  - AIM: To quantify home opioid use after cesarean delivery and identify factors
      associated with increased opioid use. METHODS: A convenience sample of women
      discharged by postoperative day 2 following a term cesarean delivery of a
      singleton fetus from May 2015 to May 2016 were contacted 2 weeks post-partum and
      questioned regarding opioid use, pain control and pain expectations. RESULTS:
      Among 141 women included in the analysis, the median number of opioid tablets
      used was 36 (interquartile range 16-45) and the median number prescribed was 60
      (interquartile range 42-65). Logistic regression identified operative time >=59.5
      min and number of opioid tablets prescribed as two factors independently
      associated with opioid use in the top quartile. CONCLUSION: In the first 2 weeks
      post-partum, 75% of women used 45 or fewer opioid tablets. Operative time over 1
      h and increased number of opioid tablets prescribed are factors associated with
      higher post-partum opioid use.

PMID- 29359387
TI  - Impact of the 2016 Kumamoto Earthquake on a female patient with ornithine
      transcarbamoylase deficiency.

PMID- 29359388
TI  - Three-dimensional prototyping for procedural simulation of transcatheter mitral
      valve replacement in patients with mitral annular calcification.
AB  - INTRODUCTION: Three-dimensional (3D) prototyping is a novel technology which can
      be used to plan and guide complex procedures such as transcatheter mitral valve
      replacement (TMVR). METHODS: Eight patients with severe mitral annular
      calcification (MAC) underwent TMVR. 3D digital models with digital balloon
      expandable valves were created from pre-procedure CT scans using dedicated
      software. Five models were printed. These models were used to assess prosthesis
      sizing, anchoring, expansion, paravalvular gaps, left ventricular outflow tract
      (LVOT) obstruction, and other potential procedure pitfalls. Results of 3D
      prototyping were then compared to post procedural imaging to determine how
      closely the achieved procedural result mirrored the 3D modeled result. RESULTS:
      3D prototyping simulated LVOT obstruction in one patient who developed it and in
      another patient who underwent alcohol septal ablation prior to TMVR. Valve sizing
      correlated with actual placed valve size in six out of the eight patients and
      more than mild paravalvular leak (PVL) was simulated in two of the three patients
      who had it. Patients who had mismatch between their modeled valve size and post
      procedural imaging were the ones that had anterior leaflet resection which could
      have altered valve sizing and PVL simulation. 3D printed model of one of the
      latter patients allowed modification of anterior leaflet to simulate surgical
      resection and was able to estimate the size and location of the PVL after
      inserting a valve stent into the physical model. CONCLUSION: 3D prototyping in
      TMVR for severe MAC is feasible for simulating valve sizing, apposition,
      expansion, PVL, and LVOT obstruction.

PMID- 29359389
TI  - Hepatitis C virus direct-acting antivirals therapy impacts on extracellular
      vesicles microRNAs content and on their immunomodulating properties.
AB  - BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is known to cause major
      alterations in the cross-talk between hepatic and immune cells thus contributing
      to the liver disease pathogenesis. Extracellular vesicles have been proved to act
      as major players in cell-cell communication, and their cargo changes in relation
      to pathophysiological states. The aim of this study was to evaluate the effects
      of chronic HCV infection and direct-acting antivirals (DAA) on exosome-delivered
      microRNAs and on their ability to modulate the innate immune response. METHODS:
      Exosomes isolated from the plasma of healthy donors and naive, viremic HCV
      patients before and after DAA treatment have been compared for their microRNAs
      cargo by quantitative polymerase chain reaction. Functional assays with
      peripheral blood cells from healthy donors were performed to assess exosome
      mediated immune responses. RESULTS: MicroRNAs associated with HCV-related
      immunopathogenesis which were found to be enriched in exosomes of HCV viremic
      patients (in particular, miR-122-5p, miR-222-3p, miR-146a, miR-150-5p, miR-30c,
      miR-378a-3p and miR-20a-5p) were markedly reduced by DAA therapy. This exosome
      microRNA cargo modulation parallels changes in their immunomodulatory properties
      in ex vivo experiments. Exosomes from HCV patients inhibit NK degranulation
      activity and this effect correlates with miR-122-5p or miR-222-3p levels.
      CONCLUSIONS: Enrichment of immunomodulatory microRNAs in exosomes of HCV patients
      was correlated with their inhibitory activity on innate immune cells function.
      Direct-acting antivirals (DAA) treatment was observed to revert both microRNA
      content and functional profiles of systemic exosomes towards those of healthy
      donors. Exosome-associated microRNAs may provide valuable biomarkers to monitor
      immune response recovery.

PMID- 29359390
TI  - Dual antiplatelet therapy after coronary drug-eluting stent implantation in
      China: A large single center study.
AB  - OBJECTIVE: To investigate the actual dual antiplatelet therapy (DAPT) duration
      after drug-eluting stent (DES) treatment in China. BACKGROUND: Currently, less is
      known about actual DAPT duration after drug-eluting stent (DES) treatment in
      China. Here, we performed a study in the largest cardiovascular center in China
      to investigate DAPT duration and identify associated factors after DES
      implantation. METHODS: A total of 9,919 consecutive patients with DES
      implantation from January 2013 to December 2013 were enrolled. DAPT cessation was
      observed, and factors associated with different DAPT durations were analyzed.
      RESULTS: The median follow-up time was 882 days. The proportion of patients with
      DAPT coverage at 1-year of follow-up was 97.3%, and it decreased to 30.1% for 2
      years. The distribution of DAPT duration was not significantly different among
      patients with acute myocardial infarction (AMI) versus non-AMI (P = 0.41) and
      with new-generation DES versus first-generation DES (P = 0.54). The multivariable
      analysis indicated some independent predictors prolonging DAPT duration,
      including target vessel revascularization (OR 2.50, 95% CI 2.04-3.06, P < 0.001),
      stent numbers (OR 1.10, 95% CI 1.05-1.15, P < 0.001), and previous coronary
      artery bypass grafting (OR 0.76, 95% CI 0.61-0.96, P = 0.02). Other clinical
      factors, such as the increased risk of bleeding and high ischemic risk, were not
      associated with DAPT duration. CONCLUSIONS: The 1-year DAPT after DES was applied
      to 97.3% of Chinese patients in the studied clinical center. However, the DAPT
      duration after 1 year was not adjusted according to the patients' bleeding
      situation and ischemic risks.

PMID- 29359391
TI  - Angiographic follow-up of infants and children undergoing percutaneous carotid
      artery interventions.
AB  - OBJECTIVE: The purpose of this study was to review the outcomes following the
      percutaneous carotid arterial (PCA) approach in infants and children with
      congenital heart disease. BACKGROUND: PCA access is becoming more commonly
      adopted following reports demonstrating it is a safe alternative to surgical
      carotid cutdown and even the femoral arterial route. However, follow-up outcomes
      after PCA remain unreported. METHODS: We reviewed all cases with PCA access and
      follow-up catheterizations which included carotid artery (CA) angiography between
      May 2012 until December 2016. We examined for evidence of CA stenosis at follow
      up angiography and assessed any other CA complications associated with vascular
      access. RESULTS: There were 61 PCA catheterizations performed in 55 unique
      patients. Follow-up CA imaging with angiography was available in 43 patients
      (78%, 43/55). There was no vessel stenosis nor lumen irregularity in 28 (65%)
      patients. In 15 cases (35%), there was a mild degree of irregularity or narrowing
      by angiography (median 4.1%, range 2.3%-12.5%). Nine patients underwent repeat
      PCA catheterizations. Seven of these had no visible vascular stenosis on follow
      up angiographic imaging, including a patient who was accessed three separate
      times from the CA. No statistically significant risk factors for developing mild
      CA stenosis were identified. CONCLUSIONS: PCA access for pediatric interventional
      catheterization appears to be safe with a very low rate of mild stenosis, and
      very few complications. Follow-up outcomes in our series are excellent, with a CA
      patency rate of 100%, even after multiple procedures. Mild CA stenosis was not
      associated with patient size or sheath introducer caliber. While the acute
      results from percutaneous CA catheterization have proven safe in recent
      literature, longer-term outcomes remain unreported. At our institution, the
      outcomes following percutaneous carotid access are associated with an excellent
      patency rate of 100%, even after multiple procedures on the same vessel. A low
      incidence of mild vessel stenosis can be appreciated on follow-up angiography.

PMID- 29359392
TI  - Importance of phosphoinositide binding by human beta-defensin 3 for Akt-dependent
      cytokine induction.
AB  - Host defense peptides (HDPs) are well-characterized for their antimicrobial
      activities but also variously display potent immunomodulatory effects. Human beta
      defensin 3 (HBD-3) belongs to a well-known HDP family known as defensins and is
      able to induce leukocyte chemotactic recruitment, leukocyte
      activation/maturation, proinflammatory cytokine release, and co-stimulatory
      marker expression. HBD-3-stimulated cytokine induction is NF-kappaB-dependent and
      was initially suggested to act via G protein-coupled C-C chemokine receptor
      phospholipase C (PLC) and/or Toll-like receptor signaling. Subsequent
      pharmacological inhibition, however, revealed that NF-kappaB activation by HBD-3
      is receptor-independent and instead involves the phosphoinositide 3-kinase (PI3K)
      protein kinase B (Akt) pathway, the mechanism of which remains undetermined.
      Recently, we have shown that HBD-3 can enter mammalian cells and bind to inner
      membrane phosphoinositide 4,5-bisphosphate [PI(4,5)P2], an important second lipid
      messenger of PLC and PI3K-Akt pathways. In this study, we report that the
      interaction of HBD-3 with PI(4,5)P2 is important for PI3K-Akt-NF-kappaBeta
      mediated induction of tumor necrosis factor and interleukin-6. These data provide
      insights into the mechanism of immunomodulation by HBD-3, and more generally,
      highlight the complex multifaceted signaling roles of HDPs in innate defense.
      Furthermore, it is suggested that the proposed mode of action may be conserved in
      other HDPs.

PMID- 29359394
TI  - Rethinking status dystonicus: A welcome start to a challenging problem.

PMID- 29359393
TI  - A novel kinase function of a nucleoside-diphosphate-kinase homologue in
      Porphyromonas gingivalis is critical in subversion of host cell apoptosis by
      targeting heat-shock protein 27.
AB  - We have previously shown that a homologue of a conserved nucleoside-diphosphate
      kinase (Ndk) family of multifunctional enzymes and secreted molecule in
      Porphyromonas gingivalis can modulate select host molecular pathways including
      downregulation of reactive-oxygen-species generation to promote bacterial
      survival in human gingival epithelial cells (GECs). In this study, we describe a
      novel kinase function for bacterial effector, P. gingivalis-Ndk, in abrogating
      epithelial cell death by phosphorylating heat-shock protein 27 (HSP27) in GECs.
      Infection by P. gingivalis was recently suggested to increase phosphorylation of
      HSP27 in cancer-epithelial cells; however, the mechanism and biological
      significance of antiapoptotic phospho-HSP27 during infection has never been
      characterised. Interestingly, using glutathione S-transferase-rNdk pull-down
      analysed by mass spectrometry, we identified HSP27 in GECs as a strong binder of
      P. gingivalis-Ndk and further verified using confocal microscopy and ELISA.
      Therefore, we hypothesised P. gingivalis-Ndk can phosphorylate HSP27 for
      inhibition of apoptosis in GECs. We further employed P. gingivalis-Ndk protein
      constructs and an isogenic P. gingivalis-ndk-deficient-mutant strain for
      functional examination. P. gingivalis-infected GECs displayed significantly
      increased phospho-HSP27 compared with ndk-deficient-strain during 24 hr
      infection. Phospho-HSP27 was significantly increased by transfection of GFP
      tagged-Ndk into uninfected-GECs, and in vitro phosphorylation assays revealed
      direct phosphorylation of HSP27 at serines 78 and 82 by P. gingivalis-Ndk.
      Depletion of HSP27 via siRNA significantly reversed resistance against
      staurosporine-mediated-apoptosis during infection. Transfection of recombinant P.
      gingivalis-Ndk protein into GECs substantially decreased staurosporine-induced
      apoptosis. Finally, ndk-deficient-mutant strain was unable to inhibit
      staurosporine-induced Cytochrome C release/Caspase-9 activation. Thus, we show
      for the first time the phosphorylation of HSP27 by a bacterial effector-P.
      gingivalis-Ndk-and a novel function of Ndks that is directly involved in
      inhibition of host cell apoptosis and the subsequent bacterial survival.

PMID- 29359395
TI  - Intentional longitudinal and side-cell stent fractures: Intermediate term follow
      up.
AB  - BACKGROUND: Use of small diameter stents in young children and jailing of side
      branches pose significant challenges to future re-interventions. We sought to
      assess the capacity to induce longitudinal fractures in undersized stents to
      increase vessel diameter, and side cell fractures to enlarge stenotic jailed
      branches. METHODS: Retrospective review of patients who underwent attempted
      intentional stent fractures (ISF) from 01/06-02/17. RESULTS: Twenty-two patients,
      median age 4.4 (1.1-47.8) years, weighing 14.3 (6.9-102) kg underwent attempted
      ISF in 32 vessels. Initial stent implant occurred at a median age of 1.0 (0.1
      34.1) years, at the following sites: pulmonary arteries (11), pulmonary veins
      (14), systemic veins (6), and aorta (1). Initial diameters of the stents were 3.5
      12 mm. Thirteen vessels had overlapping stents. Using high-pressure balloons,
      longitudinal ISF was achieved in 23 and side cell ISF in eight vessels. One
      longitudinal ISF attempt was unsuccessful. Three lesions were immediately re
      stented after longitudinal ISF, and three lesions treated with angioplasty (1) or
      stenting (2) after side cell ISF. Only one complication occurred (pseudoaneurysm
      in a pulmonary artery after longitudinal ISF requiring placement of a covered
      stent). At a median follow up of 2.0 years (2 days - 10.8 years), eight patients
      had 16 additional interventions for restenosis at site of ISF. CONCLUSIONS: ISF
      can be induced safely in a variety of vascular beds using high-pressure balloons
      both longitudinally or through side cells. Longitudinal ISF only rarely requires
      immediate placement of a new stent; however, late restenosis may occur, requiring
      re-stenting.

PMID- 29359396
TI  - Association between cotinine-verified smoking status and risk of nonalcoholic
      fatty liver disease.
AB  - BACKGROUND & AIMS: The relationship between cigarette smoking and nonalcoholic
      fatty liver disease (NAFLD) has been controversial. Most relevant studies have
      relied on self-reported questionnaires. We aimed to elucidate the association
      between smoking status and NAFLD using an objective biomarker of tobacco exposure
      (urinary cotinine) and self-reported questionnaire. METHODS: A cross-sectional
      study was conducted on 160 862 asymptomatic examinees who underwent abdominal
      ultrasonography and urinary cotinine measurements between April 2011 and December
      2015. Cotinine-verified current smokers were defined as participants with urinary
      cotinine levels >=50 ng/mL. RESULTS: The mean age of the study population was
      36.1 years, and the proportion of men was 51.7%. The proportions of self-reported
      and cotinine-verified current smokers were 17.6% and 17.7% respectively. After
      adjusting for confounding factors, self-reported current smoking was associated
      with an increased risk of NAFLD (adjusted odds ratio [AOR], 1.10; 95% confidence
      interval [CI], 1.06-1.14). Moreover, among the current smokers, the risk of NAFLD
      increased with an increase in the amount of cigarette smoking (<10 and >=10 pack
      years vs never smokers; AOR, 1.04 and 1.11; 95% CI, 1.01-1.08 and 1.05-1.16
      respectively). Cotinine-verified current smoking was also associated with an
      increased risk of NAFLD (AOR, 1.10; 95% CI, 1.06-1.14). CONCLUSIONS: Cotinine
      verified current smoking and self-reported current smoking were independent risk
      factors for NAFLD. Further longitudinal studies are needed to more clearly
      elucidate the impact of smoking on the development of NAFLD.

PMID- 29359397
TI  - Recovery orientation in mental health inpatient settings: Inpatient experiences?
AB  - Offering mental health treatment in line with a recovery-oriented practice has
      become an objective in the mental health services in many countries. However,
      applying recovery-oriented practice in inpatient settings seems challenged by
      unclear and diverging definitions of the concept in and the organization of these
      settings. In Denmark, educational and organizational efforts have been made to
      organize inpatient services with a recovery-oriented approach. Hence, we aimed to
      explore whether and how these efforts are reflected in the inpatients'
      experiences of their care and treatment. Semi-structured interviews were
      conducted with 14 inpatients from two mental health inpatient wards using an
      interview guide based on factors from the Recovery Self-Assessment. Qualitative
      content analysis was applied in the analysis. Six themes covering the
      participants' experiences were identified. The participants felt accepted and
      protected in the ward and found comfort in being around other people but missed
      talking and engaging with health professionals. They described limited choice and
      influence on the course of their treatment, and low information levels regarding
      their treatment, which they considered to consist predominantly of medication.
      Furthermore, they described feeling continuously observed and assessed from a
      distance by health professionals. Like the sparse previous research among
      inpatients, the results highlight ambivalent experiences of health professionals'
      support and ward structure as well as the medical treatment hegemony. As such,
      the educational and organizational efforts of introducing recovery-oriented
      practices in the wards seemed not very well reflected in the participants'
      experiences of their stay.

PMID- 29359398
TI  - External validation of the prostascore model in patients with metastatic hormone
      sensitive prostate cancer recruited to the CHAARTED study.
AB  - OBJECTIVE: To externally validate 'prostascore' in patients with metastatic
      hormone-sensitive prostate cancer recruited to the phase III CHAARTED study.
      METHODS: We conducted a retrospective analysis of the prospectively collected
      data from patients with metastatic hormone-sensitive prostate cancer in the
      CHAARTED study, a phase III multicentre study conducted between 2006 and 2014.
      The main outcome of the present analysis was overall survival, assessed using
      Kaplan-Meier analysis or log-rank testing, in the whole cohort according to
      different prostascores. In addition, patients with different scores were compared
      according to treatment arm. RESULTS: A total of 702 cases had complete baseline
      data, allowing calculation of prostascores and inclusion in the present analysis.
      Overall survival was assessed according to prostascores in the entire cohort and
      the P value for overall survival trend was significant (P < 0.001). Likewise,
      progression-free survival was assessed according to prostascores in the entire
      cohort and the P value for progression-free survival trend was also significant
      (P < 0.001). Overall survival comparisons according to treatment arm were
      evaluated among different prostascores. Notably, the P value for overall survival
      difference was not significant for a prostascore = 2 (P = 0.702), but was
      significant for scores of 3, 4 and 5 (P < 0.05). The cause-specific hazard ratio
      for cancer-specific survival (adjusted for treatment arm used) was also
      evaluated. The P value for pairwise comparisons between different scores was
      significant (P < 0.01) except for the comparison between scores 4 and 5.
      CONCLUSION: The present study further confirms the role of prostascore in
      predicting the outcomes of patients with metastatic hormone-sensitive prostate
      cancer and also highlights its potential role in therapeutic decision-making.

PMID- 29359399
TI  - Review: The international consensus classification of Focal Cortical Dysplasia -
      a critical update 2018.
AB  - The Diagnostic Methods commission of the International League against Epilepsy
      (ILAE) released a first international consensus classification of Focal Cortical
      Dysplasia (FCD) in 2011. Since that time, this FCD classification has been widely
      used in clinical diagnosis and research (more than 740 papers cited in Pubmed
      between 1/1/2012 and 7/1/2017). Herein, we review the new data that will inform
      and revise the FCD classification. Many recent papers described molecular-genetic
      characteristics in FCD type II including multiple mutations in the mTOR pathway.
      In addition, the electro-clinico-imaging phenotype and surgical outcomes of FCD
      type II (in particular type IIb) were further defined and validated. These
      results pave the way for the design of an integrated clinico-pathological and
      genetic classification system, as recently recommended by the WHO for the
      classification of malignant brain tumours. On the other hand, little new
      information was acquired on FCD types I and III. Focal cortical dysplasia type I
      subtypes are still lacking a comprehensive description of clinical phenotypes,
      reproducible imaging characteristics, and specific molecular/genetic biomarkers.
      Associated FCD III subtypes also became rare in published literature. Despite
      temporal lobe epilepsy being the most common focal epilepsy in adults, we have
      not identified neurophysiological, imaging, histopathological and/or genetic
      biomarkers to reliably classify FCD III with or without hippocampal sclerosis. In
      respect of pathogenesis, FCD adjacent to a non-developmental, postnatally
      acquired lesion is difficult to explain and perhaps does not exist. This update
      may help foster shared efforts towards a better understanding of FCD, potential
      future updates of classification and novel targeted treatments.

PMID- 29359400
TI  - Biosynthesis and Characterization of Copper Nanoparticles Using Shewanella
      oneidensis: Application for Click Chemistry.
AB  - Copper nanoparticles (Cu-NPs) have a wide range of applications as heterogeneous
      catalysts. In this study, a novel green biosynthesis route for producing Cu-NPs
      using the metal-reducing bacterium, Shewanella oneidensis is demonstrated. Thin
      section transmission electron microscopy shows that the Cu-NPs are predominantly
      intracellular and present in a typical size range of 20-40 nm. Serial block-face
      scanning electron microscopy demonstrates the Cu-NPs are well-dispersed across
      the 3D structure of the cells. X-ray absorption near-edge spectroscopy and
      extended X-ray absorption fine-structure spectroscopy analysis show the
      nanoparticles are Cu(0), however, atomic resolution images and electron energy
      loss spectroscopy suggest partial oxidation of the surface layer to Cu2 O upon
      exposure to air. The catalytic activity of the Cu-NPs is demonstrated in an
      archetypal "click chemistry" reaction, generating good yields during azide-alkyne
      cycloadditions, most likely catalyzed by the Cu(I) surface layer of the
      nanoparticles. Furthermore, cytochrome deletion mutants suggest a novel metal
      reduction system is involved in enzymatic Cu(II) reduction and Cu-NP synthesis,
      which is not dependent on the Mtr pathway commonly used to reduce other high
      oxidation state metals in this bacterium. This work demonstrates a novel, simple,
      green biosynthesis method for producing efficient copper nanoparticle catalysts.

PMID- 29359401
TI  - An independent race model involving an abort and re-plan strategy explains reach
      redirecting movements during planning and execution.
AB  - Although race models have been extensively used to study inhibitory control, the
      mechanisms that enable change of reach plans in the context of race models remain
      unexplored. We used a redirect task in which targets occasionally changed their
      locations to study the control of reaching movements during movement planning and
      execution phases. We tested nine different race model architectures that could
      explain the redirect behavior of reaching movements. We show that an independent
      GO-STOP-GO model that reflects a plan-abort-re-plan strategy involving non
      interacting elements successfully explained the various behavioral measures such
      as the compensation function and the pattern of error response reaction times. By
      extending the same race model to the execution phase, we could explain the extent
      and the pattern of hypometric trials. Interestingly, the race model also provided
      evidence that redirecting a movement during planning and execution shared the
      same inhibitory mechanism. Taken together, this study demonstrates the
      applicability of an independent race model to understand the computational
      mechanisms underlying the control of reach movements.

PMID- 29359402
TI  - Incidence, predictors, and midterm clinical outcomes of left ventricular
      obstruction after transcatheter aortic valve implantation.
AB  - OBJECTIVES: We aimed to evaluate the incidence and midterm clinical outcomes of
      left ventricular obstruction (LVO) after transcatheter aortic valve implantation
      (TAVI). BACKGROUNDS: LVO is occasionally unmasked following valve replacement for
      severe aortic stenosis. However, little is known about the prevalence and effects
      of LVO after TAVI. METHODS: A total of 158 patients who underwent TAVI in our
      center between October 2013 and November 2015 received echocardiographic
      evaluations at baseline; before hospital discharge; and at 3, 6, and 12 months
      after TAVI. LVO was defined as a peak pressure gradient >30 mm Hg. RESULTS: Over
      1 year of follow-up after TAVI, 21 patients (13.3%) demonstrated postprocedural
      LVO. The incidence was highest at 3-months follow-up and decreased at 6 months or
      later. Of the 21 patients with LVO, 20 (95.2%) demonstrated midventricular
      obstruction (MVO), whereas only 1 (4.8%) showed obstruction of the outflow tract
      (LVOT) with systolic anterior motion (SAM) of the mitral leaflet. In a
      multivariate analysis, the LVOT diameter (odds ratio [OR], 0.45; 95% confidence
      interval [CI], 0.30-0.67; P < 0.001), transvalvular velocity (OR, 2.44; 95% CI,
      1.13-5.26; P = 0.023), and the presence of accelerated intraventricular flow at
      baseline (OR, 6.13; 95% CI, 1.49-25.2; P = 0.012) were associated with the
      occurrence of LVO. Postprocedural LVO was not associated with midterm all-cause
      death or heart failure events. CONCLUSION: In patients who underwent TAVI, MVO
      occurred more often than LVOT obstruction. However, the occurrence of
      postprocedural LVO was not associated with worsened clinical outcomes in these
      patients.

PMID- 29359403
TI  - Previous exposure to chronic intermittent hypoxia blunts the development of one
      kidney, one-clip hypertension in rats.
AB  - NEW FINDINGS: What is the central question of this study? Chronic intermittent
      hypoxia (CIH) and one-kidney, one-clip experimental models lead to sympathetic
      overactivity and hypertension. The present study explored the impact of previous
      exposure to CIH on one-kidney, one-clip renal hypertension; we hypothesized that
      CIH potentiates its development. What is the main finding and its importance? The
      development of one-kidney, one-clip renal hypertension was attenuated by previous
      exposure to CIH, and this protective effect was eliminated by carotid body
      denervation. These findings indicate that inputs from peripheral chemoreceptors
      in CIH-preconditioned rats play a role in preventing the increase in sympathetic
      activity and arterial pressure induced by one-kidney, one-clip renal
      hypertension. ABSTRACT: Chronic intermittent hypoxia (CIH) and one-kidney, one
      clip (1K, 1C) experimental models lead to sympathetic overactivity and
      hypertension. We hypothesized that previous exposure to CIH potentiates the
      development of 1K, 1C renal hypertension. Male rats were divided into the
      following four groups: Control-1K, 1C, maintained under normoxia followed by 1K,
      1C surgery (n = 19); Control-Sham, maintained under normoxia, followed by sham
      surgery (n = 19); CIH-1K, 1C, exposed to CIH (10 days) and 1K, 1C surgery (n =
      19); and CIH-Sham, exposed to CIH and sham surgery (n = 18). Animals were
      catheterized 8 days after 1K, 1C or Sham surgeries and cardiovascular and
      respiratory parameters recorded on the following day. Baseline mean arterial
      pressure was higher in Control-1K, 1C than in Control-Sham rats (P < 0.05) and
      was higher in CIH-1K, 1C than in CIH-Sham rats (P < 0.05). However, the increase
      in mean arterial pressure in CIH-1K, 1C animals was significantly blunted in
      comparison to Con-1K, 1C rats (P < 0.05), indicating that previous exposure to
      CIH attenuates the development of renal hypertension. Systemic administration of
      hexamethonium, a ganglionic blocker, promoted a larger hypotensive response in
      Con-1K, 1C compared with CIH-1K, 1C rats (P < 0.05), suggesting that sympathetic
      activity was attenuated in rats previously exposed to the CIH protocol. In
      addition, removal of the carotid bodies before 1K, 1C renal hypertension
      eliminated the protective effect of CIH preconditioning on the development of the
      1K, 1C hypertension. We conclude that previous exposure to CIH attenuates the
      development of renal hypertension via a carotid body-dependent mechanism.

PMID- 29359405
TI  - Low-temperature, Low-Energy, and High-Efficiency Pretreatment Technology for
      Large Wood Chips with a Redox Couple Catalyst.
AB  - The pretreatment of lignocellulosic biomass plays a vital role in the conversion
      of cellulosic biomass to bioethanol, especially for softwoods and hardwoods.
      Although many pretreatment technologies have been reported so far, only a few
      pretreatment methods can handle large woodchips directly. To improve the
      efficiency of pretreatment, existing technologies require the grinding of the
      wood into small particles, which is an energy-consuming process. Herein, for the
      first time, we report a simple, effective, and low-temperature (~100  degrees C)
      process for the pretreatment of hardwood (HW) and softwood (SW) chips directly by
      using a catalytic system of FeCl3 /NaNO3 (FCSNRC). The pretreatment experiments
      were conducted systematically, and a conversion of 71.53 and 70.66 % of cellulose
      to sugar could be obtained for the direct use of large HW and SW chips. The new
      method reported here overcomes one of the critical barriers in biomass-to-biofuel
      conversion, and both grinding and thermal energies can be reduced significantly.

PMID- 29359404
TI  - Heterogeneity of memory B cells.
AB  - Potential solid organ transplant recipients broadly sensitized to HLA have long
      wait times, low transplant rates and poor outcomes. The new kidney allocation
      system has improved access to the most highly sensitized recipients; however,
      their long-term outcomes are unknown. Emerging data suggest that memory B cell
      repertoire is broader than the plasma cell repertoire, therefore, despite
      refinements in anti-HLA antibody detection technology, donor-specific HLA-
      specific memory B cells may in fact be present in some, if not most, highly
      sensitized recipients with no detectable donor-specific antibodies. In addition,
      new findings have underscored the heterogeneity in memory B cell generation, and
      in the signals that determine memory versus plasma cell fate during primary
      antigen encounter, as well as memory B cell differentiation upon antigen
      reencounter into plasma cells or reentry into germinal centers to subsequently
      emerge as higher affinity and class-switched plasma cells. Thus, heterogeneity
      memory B cells generation may affect the efficacy of specific immunomodulation
      during the recall response. We propose that the ability to quantify donor
      specific B cell in transplant recipients is urgently required to provide insights
      into the mechanisms of sensitization and recall, and for the early detection of
      acute and chronic AMR.

PMID- 29359406
TI  - Validation of the V-RESOLVE (Visual Estimation for Risk prEdiction of Side Branch
      OccLusion in Coronary Bifurcation interVEntion) score system.
AB  - OBJECTIVES: This study sought to validate the V-RESOLVE score system. BACKGROUND:
      The V-RESOLVE score was developed to predict the risk of side branch (SB)
      occlusion after stenting in the main vessel (MV) of coronary bifurcation lesions
      based on visual estimation of the angiographic data, but it needed to be
      validated. METHODS: From January to June 2013, 1,286 patients with 1,820
      bifurcation lesions undergoing elective intervention with provisional strategy
      were included. Angiographic data before MV stenting were reviewed, and the V
      RESOLVE score was calculated. SB occlusion was defined as any decrease in
      thrombolysis in myocardial infarction (TIMI) flow grade or the absence of flow in
      the SB after MV stenting. The statistical performance of the prediction model was
      assessed by its discrimination, calibration, and clinical usefulness. RESULTS: SB
      occlusion occurred in 222 (12.20%) of 1,820 bifurcation lesions. The
      discrimination of the V-RESOLVE score for the validation cohort was good [C
      statistic: 0.80, 95% confidence interval (CI) 0.77-0.84]. Regarding calibration
      performance, the calibration-in-the-large was -0.03 (95% CI: -0.181 to 0.12),
      while the combined predictive effect was slightly enlarged (calibration slope:
      1.25, 95% CI: 1.081-1.41) and, mainly attributed to the stronger predictive
      effect of the diameter stenosis of the SB before MV stenting. Stratified by the V
      RESOLVE score, the SB occlusion rate was significantly higher in the high-risk
      group (26.18%) than in the non-high-risk group (3.48%). CONCLUSIONS: The V
      RESOLVE score system is a useful tool to help risk prediction for SB occlusion
      and decision-making in bifurcation intervention.

PMID- 29359408
TI  - The "double stingray technique" for recanalizing chronic total occlusions with
      bifurcation at the distal cap.
AB  - Antegrade dissection re-entry is often discouraged for chronic total occlusions
      (CTOs) with a bifurcation at the distal cap due to risk of side branch occlusion
      that can lead to periprocedural myocardial infarction and incomplete
      revascularization. Antegrade dissection re-entry, however, is often needed,
      especially in complex cases. We present the novel "double Stingray technique" for
      CTOs involving bifurcations, in which the Stingray system is used twice for re
      entry into both vessel branches, followed by two-stent bifurcation stenting to
      maintain the patency of both branches.

PMID- 29359407
TI  - The T-cell fingerprint of MALT1 paracaspase revealed by selective inhibition.
AB  - Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is
      essential for immune responses triggered by antigen receptors but the
      contribution of its paracaspase activity is not fully understood. Here, we
      studied how MALT1 proteolytic function regulates T-cell activation and fate after
      engagement of the T-cell receptor pathway. We show that MLT-827, a potent and
      selective MALT1 paracaspase inhibitor, does not prevent the initial phase of T
      cell activation, in contrast to the pan-protein kinase C inhibitor AEB071.
      However, MLT-827 strongly impacted cell expansion after activation. We
      demonstrate this is the consequence of profound inhibition of IL-2 production as
      well as reduced expression of the IL-2 receptor alpha subunit (CD25), resulting
      from defective canonical NF-kappaB activation and accelerated mRNA turnover
      mechanisms. Accordingly, MLT-827 revealed a unique transcriptional fingerprint of
      MALT1 protease activity, providing evidence for broad control of T-cell signaling
      pathways. Altogether, this first report with a potent and selective inhibitor
      elucidates how MALT1 paracaspase activity integrates several T-cell activation
      pathways and indirectly controls gamma-chain receptor dependent survival, to
      impact on T-cell expansion.

PMID- 29359409
TI  - Supra-annular valve strategy for an early degenerated transcatheter balloon
      expandable heart valve.
AB  - Currently, there are no recommendations regarding the selection of valve type for
      a transcatheter heart valve (THV)-in-THV procedure. A supra-annular valve design
      may be superior in that it results in a larger effective orifice area and may
      have a lower chance of valve thrombosis after THV-in-THV. In this report, we
      describe the use of a supra-annular valve strategy for an early degenerated THV.

PMID- 29359410
TI  - Reply to the letter regarding our manuscript 'Development and internal validation
      of the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU)'.

PMID- 29359411
TI  - Parainfluenza virus type 3 outbreak in a neonatal intensive care unit.
AB  - Parainfluenza virus (PIV) is a respiratory pathogen in young children and is
      second only to the respiratory syncytial virus (RSV) as a cause of lower
      respiratory tract infection. PIV type 3 (PIV3) is the most severe. Herein we
      describe an outbreak of PIV3 in three infants in a neonatal intensive care unit.
      They were diagnosed on virus culture from pharyngeal swabs. We prevented the
      spread of the virus using standard infection control procedures and isolation of
      the symptomatic infants. One infant had severe chronic lung disease and was
      complicated with recurrent wheezing for a long time. Because RSV and PIV have
      many structural, pathogenic, epidemiologic, and clinical similarities, we
      speculate that PIV infection causes recurrent wheezing, as observed with RSV
      infection. Therefore, physicians must consider recurrent wheezing at the time of
      treatment of PIV infection early in life.

PMID- 29359412
TI  - Influences of dietary supplementation with Lepidium meyenii (Maca) on stallion
      sperm production and on preservation of sperm quality during storage at 5 
      degrees C.
AB  - Stallion semen is damaged by oxidative stress during cooling and transport. Semen
      processing and extenders have been tested to improve the fertilizing capacity of
      semen and to preserve semen during transport. Dietary supplementation with
      natural antioxidants has been proposed to prevent oxidative damages. In this
      study, for the first time, the effect of dietary supplementation with Lepidium
      meyenii (Maca) on the characteristics of fresh and chilled stallion semen was
      evaluated. Maca is a traditional Andean crop used as a nutraceutical for the
      fertility-enhancing properties that are linked with antioxidant activity. The
      diet of five stallions was supplemented with 20 g of Maca powder daily for a
      total of 60 days. A control group of five stallions received the same diet
      without Maca. Semen was collected once before the administration of Maca (D0),
      twice during the administration at 30 and 60 days (D30 and D60), and finally
      twice at 30 and 60 days after the end of the administration (D90 and D120).
      Ejaculates were processed for cooled shipping at 5  degrees C and evaluated in
      the laboratory for total and progressive motility, acrosome integrity, and lipid
      peroxidation after collection and after 24, 48, and 72 h of storage. Dietary
      supplementation with Maca improved sperm concentration (from 213 +/- 80.4 to 447
      +/- 73.1 * 106 spz/mL) and total sperm count (from 10,880 +/- 4377 to 24,783 +/-
      4419 * 106 spz). The beneficial effects of Maca supplementation on motility and
      acrosome integrity in the raw semen were detected from the end of treatment with
      Maca (D60) until the end of the study (D120). Furthermore, during cooling
      storage, total motility, progressive motility, and acrosome integrity declined
      more slowly in the Maca-treated group than in the control group. Lipid
      peroxidation did not change during cooling storage in either group and did not
      show a significant difference between the two groups. In this study, the dietary
      supplementation with Maca increased sperm production and stabilized semen quality
      during chilled storage.

PMID- 29359413
TI  - Effects of chronic ketamine on hippocampal cross-frequency coupling: implications
      for schizophrenia pathophysiology.
AB  - Disrupted neuronal oscillations have been identified as a potentially important
      biomarker for the perceptual and cognitive symptoms of schizophrenia. Emerging
      evidences suggest that interactions between different frequency bands, cross
      frequency coupling (CFC), serve an important role in integrating sensory and
      cognitive information and may contribute to disease pathophysiology. In this
      study, we investigated the effects of 14-day consecutive administration of
      ketamine (30 mg/kg i.p.) vs. saline on alterations in amplitude and changes in
      the coupling of low-frequency (0-30 Hz) phase and high-frequency (30-115 Hz)
      amplitude in the CA1 hippocampus of Long Evans rats. Intracranial electrode
      recordings were conducted pre- and post-injection while the animals performed a
      foraging task on a four-arm rectangular maze. Permutation analysis of frequency
      band-specific change in amplitudes revealed between-group differences in theta (6
      12 Hz) and slow gamma (25-50 Hz) but not fast gamma (65-100 Hz) bands at both
      slow and fast speeds. Chronic ketamine challenge resulted in decreased coupling
      (pre to post) at slow speeds but increased coupling at faster speeds, compared to
      either no or modest increased coupling in the saline group. These results
      demonstrate that chronic ketamine administration alters the interaction of low
      frequency phase and high-frequency oscillations chronically and that such
      coupling varies as a function of locomotive speed. These findings provide
      evidence for the potential relevance of CFC to the pathophysiology of
      schizophrenia.

PMID- 29359414
TI  - Maternal occupational cadmium exposure and nonsyndromic orofacial clefts.
AB  - BACKGROUND: Cigarette smoking is a well-studied risk factor for orofacial clefts
      (OFCs). Little is known about which constituents in cigarette smoke contribute to
      this teratogenicity in humans. One constituent, cadmium, has been associated with
      OFCs in animal studies; in humans, the role of maternal cadmium exposure on OFCs,
      independent of cigarette smoke, is unclear. In particular, the relation between
      maternal occupational cadmium exposure and OFCs is largely unexplored. METHODS:
      Using data from a large, population-based case-control study, we compared expert
      rater assessed maternal occupational cadmium exposure from self-reported
      occupational histories during the period 1 month before through 3 months after
      conception between OFC cases (n = 1,185) and unaffected controls (n = 2,832).
      Multivariable logistic regression analyses were used to estimate adjusted odds
      ratios (aORs) and 95% confidence intervals for any (yes/no) and cumulative (no,
      low, high exposure) occupational cadmium exposures and all OFCs, cleft lip +/-
      cleft palate (CL/P) and cleft palate (CP). RESULTS: Overall, 45 mothers (cases =
      13, controls = 32) were rated as having occupational cadmium exposure. Comparing
      all OFCs to controls, we observed inverse, nonsignificant aORs for any or low
      exposure, and positive, nonsignificant aORs for high exposure. Where data were
      available, aORs for CL/P and CP tended to parallel those for all OFCs.
      CONCLUSION: To our knowledge, this is the first study to specifically examine
      maternal occupational cadmium exposure and OFCs, using expert rater exposure
      assessment. The small numbers of exposed mothers observed, however, led to
      imprecise estimates. Continued research using more detailed occupational exposure
      assessment and increased sample sizes is recommended.

PMID- 29359416
TI  - Hospital Policy and Productivity - Evidence from German States.
AB  - Total factor productivity (TFP) growth allows for additional healthcare services
      under restricted resources. We examine whether hospital policy can stimulate
      hospital TFP growth. We exploit variation across German federal states in the
      period 1993-2013. State governments decide on hospital capacity planning (number
      of hospitals, departments, and beds), ownership, medical students, and hospital
      investment funding. We show that TFP growth in German hospital care reflects
      quality improvements rather than increases in output volumes. Second-stage
      regression results indicate that reducing the length of stay is generally a
      proper way to foster TFP growth. The effects of other hospital policies depend on
      the reimbursement scheme: Under activity-based (German Diagnosis-related Group)
      hospital funding, scope-related policies (privatization and specialization) come
      with TFP growth. Under fixed daily rate funding, scale matters to TFP (hospital
      size and occupancy rates). Differences in capitalization in East and West Germany
      allow to show that deepening capital may enhance TFP growth if capital is scarce.
      We also show that there is less scope for hospital policies after large-scale
      restructurings of the hospital sector. Copyright (c) 2016 John Wiley & Sons, Ltd.

PMID- 29359415
TI  - Interprofessional education: evaluation of a radiation therapy and medical
      physics student simulation workshop.
AB  - INTRODUCTION: Interprofessional education (IPE) involves two or more professions
      engaged in learning with, from and about each other. An initiative was undertaken
      to explore IPE for radiation therapy (RT) and medical physics (MP) students
      through a newly developed workshop based around simulated learning. The aims of
      this study were to explore RT and MP students' perceptions of working as part of
      a collaborative team and of their own and the other group's professional roles.
      Student perceptions of the simulation education tool, the virtual environment for
      radiotherapy training (VERT) system, were also investigated. METHODS: RT and MP
      students were invited to participate in a 4-hour interprofessional workshop. Pre-
      and post-workshop surveys were employed to collect demographic data, students'
      perceptions of interdisciplinary education (interdisciplinary education
      perception scale (IEPS)) and workshop evaluation (bespoke questionnaire).
      RESULTS: Fifteen students attended the workshop (RT, n = 8; MP, n = 7). Thirteen
      pre- and post-questionnaires were returned (Pre-questionnaire: RT, n = 6,
      response rate, 75%; MP, n = 7, response rate, 100%; post-questionnaire: RT, n =
      7, response rate, 87.5%; MP, n = 6, response rate 85.7%). For both student groups
      combined, IEPS scores ranged from 64 to 108 and 71 to 108 in the pre- and post
      questionnaires, respectively, with insignificant differences in the mean scores
      post-intervention (Z = -1.305, P = 0.192). Satisfaction with VERT as a simulation
      tool was high for both student groups. CONCLUSIONS: The interprofessional student
      workshop served to promote interprofessional collaboration for RT and MP
      students. VERT was reported as an appropriate education tool for this purpose,
      enabling access to virtual clinical equipment common to both student groups. It
      is suggested that IPE continues to be offered and investigated in RT and MP
      students, in order to improve effective interprofessional strategies which may
      enrich future professional collaboration.

PMID- 29359417
TI  - Real-world experience with use of Antihemophilic Factor (Recombinant), PEGylated
      for prophylaxis in severe haemophilia A.
AB  - INTRODUCTION: Prophylaxis with extended half-life factor VIII (FVIII) is approved
      for haemophilia A, but data regarding routine clinical use are limited. AIM: To
      assess real-world experience of ADYNOVATE(r) (Antihemophilic Factor
      (Recombinant), PEGylated prophylaxis in children and adults with haemophilia A.
      METHODS: A retrospective chart review was conducted in three US haemophilia
      treatment centres. Records of all patients who began Adynovate prophylaxis in
      routine clinical practice were identified. Demographic, clinical and patient
      reported information beginning 6 months before initiation of Adynovate until the
      record review was analysed. RESULTS: Fifteen patients (aged 9 months to 28
      years), with median 9 months' use of Adynovate (range 1-15 months), were
      identified. All had switched from another prophylactic regimen, 13 (87%) from
      standard half-life recombinant FVIII. Nine (60%) patients had >=1 bleed within 6
      months preswitch. The most frequent reason for switching was to reduce infusion
      frequency (14 patients). After switching, infusion frequency reduced for 13
      patients, and overall weekly factor consumption decreased by 19%. Eight (53%)
      patients had no bleeds postswitch, three (20%) had spontaneous joint bleeds (vs
      four pre-switch), and three (20%) had only mild traumatic bleeds.
      Patient/parental satisfaction with Adynovate was documented as positive in 13 of
      15 (87%) cases; 2 patients were not satisfied and discontinued Adynovate. No
      adverse events were considered related to Adynovate. CONCLUSION: In patients who
      switched from a standard half-life FVIII to Adynovate prophylaxis in routine
      clinical practice, bleeding control was generally improved or maintained, with a
      lower infusion frequency and factor consumption in most patients.

PMID- 29359418
TI  - Effective shunt closure for pulmonary hypertension and liver dysfunction in
      congenital portosystemic venous shunt.
AB  - OBJECTIVE: Congenital portosystemic venous shunt (CPSVS) is a rare vascular
      malformation with a high risk of mortality from pulmonary arterial hypertension
      (PAH), but the treatment outcome of CPSVS closure remains elusive. Our aim was to
      investigate the clinical features and establish the optimal management of CPSVS
      with or without PAH. METHODS: Twenty-four patients with CPSVS treated in Kyushu
      University Hospital between 1990 and 2015 were enrolled in this study. The
      patients were divided into a PAH group (n = 9) and a non-PAH group (n = 15).
      Clinical characteristics and outcomes were evaluated. RESULTS: The first
      manifestation of CPSVS at diagnosis (28.5 [1-216] months) was hypergalactosemia
      in 13 (54%) or PAH in six (25%) patients. PAH was the cause of all three deaths.
      The PAH group had higher levels of serum total bile acid, manganese, and total
      bilirubin, along with higher pulmonary vascular resistance index (PVRI) than the
      non-PAH group (7.2 [5.1-38.1] vs 1.2 [0.5-3.3] unit/m2 , P < 0.001). Five of nine
      PAH patients underwent CPSVS closure at a median of 38 months (range 21-118)
      after PAH diagnosis. Pulmonary artery pressure improved after CPSVS closure with
      PAH-specific therapy, but normal range was not achieved. CPSVS closure improved
      the hepatic synthetic function of four PAH patients. Eigh-t of 15 non-PAH
      patients who received CPSVS closure did not develop PAH for a median of 34.5
      months (range 6-164) after the procedure. CONCLUSIONS: CPSVS closure with PAH
      specific therapy successfully controlled PAH. Early CPSVS closure may prevent the
      occurrence and progression of PAH with CPSVS.

PMID- 29359419
TI  - Pluripotency Deconstructed.
AB  - Pluripotency denotes the flexible capacity of single cells to give rise to all
      somatic lineages and typically also the germline. Mouse ES cells and post
      implantation epiblast-derived stem cells (EpiSC) are widely used pluripotent cell
      culture systems. These two in vitro stem cell types have divergent
      characteristics. They are considered as representative of distinct developmental
      stages, distinguished by using the terms "naive" and "primed". A binary
      description is an over-simplification, however. Here, we discuss an intermediate
      stage of pluripotency that we term "formative". Formative pluripotency features a
      gene regulatory network switch from the naive state and comprises capacitation of
      enhancers, signaling pathways and epigenetic machinery in order to install
      competence for lineage specification.

PMID- 29359420
TI  - Copper-Catalyzed Highly Stereoselective Trifluoromethylation and
      Difluoroalkylation of Secondary Propargyl Sulfonates.
AB  - It is challenging to stereoselectively introduce a trifluoromethyl group (CF3 )
      into organic molecules. To date, only limited strategies involving direct
      asymmetric trifluoromethylation have been reported. Herein, we describe a new
      strategy for direct asymmetric trifluoromethylation through the copper-catalyzed
      stereospecific trifluoromethylation of optically active secondary propargyl
      sulfonates. The reaction enables propargylic trifluoromethylation with high
      regioselectivity and stereoselectivity. The reaction could also be extended to
      stereospecific propargylic difluoroalkylation. Transformations of the resulting
      enantiomerically enriched fluoroalkylated alkynes led to a variety of chiral
      fluoroalkylated compounds, thus providing a useful protocol for applications in
      the synthesis of fluorinated complexes.

PMID- 29359421
TI  - Acute myelitis associated with human herpesvirus 7 infection.

PMID- 29359422
TI  - Asthma breathomics-promising biomarkers in need of validation.

PMID- 29359423
TI  - Sense and Sensitivity: A Response to the Commentary by Keller et al. (2018).
AB  - This reply to the commentary by Keller et al. (2018) on the article "Universality
      Without Uniformity: A Culturally Inclusive Approach to Sensitive Responsiveness
      in Infant Caregiving" (Mesman et al., ) highlights key points of agreement
      emphasizing the sense of investing in synergies across research traditions. These
      include the importance of distinguishing between different parenting constructs,
      the need for more studies to test the presented theoretical assumptions, and the
      value of examining multiple caregiver sensitivity in relation to infants'
      developing membership of a community. The only point of disagreement reflects the
      rigidity versus flexibility of the sensitivity construct. This reply argues that
      it is exactly the versatility of the sensitivity construct that makes it a
      valuable building block for bridges between fields.

PMID- 29359424
TI  - Exclusion of adrenoceptor alpha 2 variants in a horse insensitive to
      medetomidine.

PMID- 29359425
TI  - Mechanism underlying the effect of long-term exposure to low dose of pesticides
      on DNA integrity.
AB  - Pesticides, including herbicides, insecticides and fungicides, are widely used in
      intensive agriculture. Recently, the long-term effects of pesticide exposure were
      found to be associated with many diseases. In this study, we evaluated the long
      term effect of low-level exposure to a mixture of pesticides on DNA damage
      response (DDR) in relation to individual detoxifying variability. A residential
      population chronically exposed to pesticides was enrolled,
      biological/environmental pesticide levels; paroxonase 1 (PON-1) activity and 192
      Q/R polymorphism and DDR were evaluated at three different periods of pesticide
      exposure. OGG1-dependent DNA repair activity was decreased in relation to
      pesticide exposure. The increase of DNA lesions and pesticide levels in the
      intensive pesticide-spraying period was independent on PON-1 activity. Next,
      human bronchial epithelial and neuronal cells were used as a model for in vitro
      evaluation of the mechanistic effect of pesticides. Pesticides induced
      mitochondrial dysfunction leading to ROS formation. ROS from mitochondria induced
      DNA damage, which in turn induced OGG1-dependent DNA repair activity through 8
      oxoguanine DNA glycosylase 1 (OGG1) expression and activation. Even though OGG1
      was overexpressed, an inhibition of its activity, associated with DNA lesion
      accumulation, was found at prolonged pesticide-exposure. A post-translational
      regulation of OGG1 by pesticide may be postulated. Taken together, long-term
      exposure to low-levels of pesticides affects DDR resulting in accumulation of DNA
      lesions that eventually may lead to cancer or neurological disorders.

PMID- 29359426
TI  - Ward nurses' experiences of the discharge process between intensive care unit and
      general ward.
AB  - BACKGROUND: Intensive care unit (ICU) discharges are challenging practices that
      carry risks for patients. Despite the existing body of knowledge, there are still
      difficulties in clinical practice concerning unplanned ICU discharges,
      specifically where there is no step-down unit. AIMS AND OBJECTIVES: The aim of
      this study was to explore general ward nurses' experiences of caring for patients
      being discharged from an ICU. DESIGN AND METHODS: Data were collected from focus
      groups and in-depth interviews with a total of 16 nurses from three different
      hospitals in Sweden. An inductive qualitative design was chosen. FINDINGS: The
      analysis revealed three themes that reflect the challenges in nursing former ICU
      patients: a vulnerable patient, nurses' powerlessness and organizational
      structure. The nurses described the challenge of nursing a fragile patient based
      on several aspects. They expressed feeling unrealistic demands when caring for a
      fragile former ICU patient. The demands were related to their own profession and
      knowledge regarding how to care for this group of patients. The organizational
      structure had an impact on how the nurses' caring practice could be realized.
      This evoked ethical concerns that the nurses had to cope with as the
      organization's care guidelines did not always favour the patients. CONCLUSIONS:
      The structure of the organization and its leadership appear to have a significant
      impact on the nurses' ability to offer patients the care they need. RELEVANCE TO
      CLINICAL PRACTICE: This study sheds light on the need for extended outreach
      services and intermediate care in order to meet the needs of patients after the
      intensive care period.

PMID- 29359427
TI  - Tobit regression for modeling mean survival time using data subject to multiple
      sources of censoring.
AB  - Mean survival time is often of inherent interest in medical and epidemiologic
      studies. In the presence of censoring and when covariate effects are of interest,
      Cox regression is the strong default, but mostly due to convenience and
      familiarity. When survival times are uncensored, covariate effects can be
      estimated as differences in mean survival through linear regression. Tobit
      regression can validly be performed through maximum likelihood when the censoring
      times are fixed (ie, known for each subject, even in cases where the outcome is
      observed). However, Tobit regression is generally inapplicable when the response
      is subject to random right censoring. We propose Tobit regression methods based
      on weighted maximum likelihood which are applicable to survival times subject to
      both fixed and random censoring times. Under the proposed approach, known right
      censoring is handled naturally through the Tobit model, with inverse probability
      of censoring weighting used to overcome random censoring. Essentially, the re
      weighting data are intended to represent those that would have been observed in
      the absence of random censoring. We develop methods for estimating the Tobit
      regression parameter, then the population mean survival time. A closed form large
      sample variance estimator is proposed for the regression parameter estimator,
      with a semiparametric bootstrap standard error estimator derived for the
      population mean. The proposed methods are easily implementable using standard
      software. Finite-sample properties are assessed through simulation. The methods
      are applied to a large cohort of patients wait-listed for kidney transplantation.

PMID- 29359428
TI  - Assessment of mechanical properties of human head tissues for trauma modelling.
AB  - Many discrepancies are found in the literature regarding the damage and
      constitutive models for head tissues as well as the values of the constants
      involved in the constitutive equations. Their proper definition is required for
      consistent numerical model performance when predicting human head behaviour, and
      hence skull fracture and brain damage. The objective of this research is to
      perform a critical review of constitutive models and damage indicators describing
      human head tissue response under impact loading. A 3D finite element human head
      model has been generated by using computed tomography images, which has been
      validated through the comparison to experimental data in the literature. The
      threshold values of the skull and the scalp that lead to fracture have been
      analysed. We conclude that (1) compact bone properties are critical in skull
      fracture, (2) the elastic constants of the cerebrospinal fluid affect the
      intracranial pressure distribution, and (3) the consideration of brain tissue as
      a nearly incompressible solid with a high (but not complete) water content offers
      pressure responses consistent with the experimental data.

PMID- 29359429
TI  - Matriarchy, Buddhism, and food security in Sanephong, Thailand.
AB  - Sanephong is a matriarchal Karen community located in western Thailand. The
      community benefits greatly from the availability of local foods, such as cereals,
      tubers, wild vegetables, mushrooms, fruits, and animals. In the first phase of
      this project, 387 distinct local foods were identified, which were shown to be
      good sources of energy, protein, and vitamins. Despite the availability of a
      variety of nutritious local foods, the majority of households surveyed expressed
      concern over a decline in local foods due to changing socio-economic and
      environmental conditions. This study used a qualitative research approach to look
      at the dual influences of matriarchy and Buddhism on food security in the
      community. Through this approach, matriarchal values central to the community
      were adopted as a framework; these included care, consensus, collaboration, and
      cosmological respect. In Sanephong, women are central to life in the community,
      and matriarchal cultural practices reflect a nurturing spirit-for both the earth
      and family. The community practices Buddhism, which is very complementary to the
      matriarchal system. A type of gift economy within the Buddhist context, known as
      dhana, transfers food from the wealthy to the poor with no expectation of
      reciprocity. Consequently, matriarchy and Buddhism jointly promote food security
      in the community. Studies of matriarchal societies help society-at-large to
      understand the potential benefits of systems that contrast the current
      patriarchal paradigm.

PMID- 29359430
TI  - Welcome from the International Union of Nutritional Sciences.

PMID- 29359431
TI  - Mother and child nutrition among the Chakhesang tribe in the state of Nagaland,
      North-East India.
AB  - Despite the importance of the nutritional status and food systems of Indigenous
      Peoples, the subject has received very little attention, especially in North-East
      India. Therefore, a community-based cross-sectional descriptive study was carried
      out among Chakhesang mothers with children under 5 years of age to evaluate their
      nutritional status and prevalence of chronic diseases in the context of their
      dietary habits. From 558 households (HHs), 661 children and 540 mothers were
      covered using standard anthropometric measurements as well as blood collection
      for haemoglobin and vitamin A. Data were collected from mothers on HH socio
      demographic particulars and infant and young child feeding practices. The results
      showed that the prevalence of underweight, stunting, and wasting among children
      <5 years of age was 14%, 22%, and 7%, respectively. The prevalence of anaemia and
      vitamin A deficiency was 26% and 33% among children <5 years, whereas it was 33%
      and 26%, respectively, among mothers. Hypertension was observed in 16% of women,
      whereas diabetes was seen in 0.8%. Approximately 35% and 24% of HHs suffered mild
      or moderate food insecurity, respectively, which was associated with literacy of
      the parents, per capita income, and family size. Utilization of the rich
      agrobiodiversity and wild foods by the Chakhesangs appears to be a strong reason
      for their better nutritional and health status as compared to the rest of India.
      Therefore, this Indigenous knowledge and food system must be documented and kept
      vital, especially in policies and intervention programmes addressing food and
      nutrition security among the Chakhesangs.

PMID- 29359432
TI  - Gender roles, food system biodiversity, and food security in Indigenous Peoples'
      communities.
AB  - Traditional knowledge and practice of Indigenous Peoples related to their food
      use and well-being is a wealth of information for academic study and for public
      health nutrition. Despite unique long-evolved heritages of knowledge of ecosystem
      resources, Indigenous Peoples comprise 15% of the global poor, but only 5% of the
      world's population, and they experience poverty, discrimination, and poor
      nutritional health at far greater rates than mainstream populations in their
      nations of residence. These disparities are unacceptable in all human rights
      frameworks, and the call to alleviate them resonates through all human
      development programmes and the United Nations organizations. The scholars
      contributing to this special issue of Maternal and Child Nutrition describe how
      gender roles and the right to food for several cultures of Indigenous Peoples can
      be fostered to protect their unique foods and traditions, providing food
      sovereignty and food and nutrition security benefits, especially for women and
      children. Aspects of societal maternal or paternal lineality and locality,
      division of labour, spirituality and decision-making are described. These factors
      structure the impact of gender roles with Indigenous worldviews on the dynamics
      of family food access, its availability and use, and the use of local food
      biodiversity. Cultures of Indigenous Peoples in Ecuador, Nigeria, Thailand,
      India, Canada, Japan, and Morocco are discussed. This publication is a work of
      the Task Force on Traditional, Indigenous and Cultural Food and Nutrition of the
      International Union of Nutritional Sciences.

PMID- 29359433
TI  - Indigenous Peoples' food systems, nutrition, and gender: Conceptual and
      methodological considerations.
AB  - Indigenous Peoples, especially women and children, are affected
      disproportionately by malnutrition and diet-related health problems. Addressing
      this requires an investigation of the structural conditions that underlie unequal
      access to resources and loss of traditional lifestyles and necessitates inclusive
      approaches that shed light onto these issues and provide strategies to leverage
      change. Indigenous Peoples' food systems are inextricably connected to land,
      which in turn is interwoven with issues of self-determination, livelihoods,
      health, cultural and spiritual heritage, and gender. Ongoing loss of land and the
      dominant agri-food model further threaten Indigenous Peoples' food systems.
      Continuing gender-based discrimination undermines the self-determination and
      rights of women and negatively impacts their health, nutritional status, and
      overall well-being, as well as the well-being of households and communities. We
      suggest that feminist political ecology and modern matriarchal studies provide
      holistic interlinking frameworks for investigating underlying issues of power and
      inequality. We further argue that a focus on the principles of respect,
      responsibility, and relationships, and an openness to different worldviews, can
      facilitate a bridging of Indigenous and Western approaches in research and
      community action conducted in partnership with Indigenous Peoples. This can
      contribute to creating new ways of knowing regarding Indigenous Peoples' food
      systems, equally valuing both knowledge systems. Indigenous Peoples' rights,
      right to food, and food sovereignty are frames that, despite some tensions, have
      the common goal of self-determination. Through their ability to inform, empower,
      and mobilize, they provide tools for social movements and communities to
      challenge existing structural inequalities and leverage social change.

PMID- 29359434
TI  - Changing gender roles and relations in food provisioning among matrilineal Khasi
      and patrilineal Chakhesang Indigenous rural People of North-East India.
AB  - Women's position in society, gender roles, and gender division of labour affect
      household food security, dietary diversity, nutritional status, and well-being of
      all household members, especially children. Building on both primary and
      secondary data, this study explores gender roles and relations in food
      provisioning among the North-East India Indigenous matrilineal Khasi and
      patrilineal Chakhesang Peoples, amid societal transition. With the use of a
      combination of ethnographic and ethnobotanical research tools, a total number of
      200 informants participated in 20 focus group discussions and 28 key informant
      interviews. The feminist political ecology framework was used to analyse the
      structural power relations influencing gender food-provisioning labour. Results
      show that both matrilineal and patrilineal women play equally crucial roles in
      agrobiodiversity management, subsistence agricultural production, and household
      food provisioning. However, customary laws shape different gender relations,
      women's status, and appreciation of women's work in the two societies. Gender
      roles appeared more flexible in the matrilineal society and more clearly defined
      in the patrilineal society, and gender relations more egalitarian among the
      Khasis while more hierarchical among the Chakhesangs. Household food-provisioning
      work and engagement in agricultural production did not seem to positively
      contribute to the social status of Chakhesang women, because these were expected
      as structural elements of the patriarchy. Current socio-cultural and economic
      changes in both Indigenous societies have altered the traditional food system,
      traditional livelihoods, and resource management practices, affecting women's
      role in household food provisioning and leading to the deterioration of women's
      status, influencing household dietary diversity, food, and nutritional security.

PMID- 29359435
TI  - Photographic Section.

PMID- 29359436
TI  - Gender roles, family relationships, and household food and nutrition security in
      Ohafia matrilineal society in Nigeria.
AB  - This study examined gender roles, family relationships, food security, and
      nutritional status of households in Ohafia: a matrilineal society in Nigeria. A
      cross-sectional descriptive study was conducted. Multistage sampling technique
      was used to select 287 households from three villages: Akanu, Amangwu, and Elu.
      Qualitative and quantitative data collection methods were adopted, namely, focus
      group discussions and questionnaires. Anthropometric measurements (height and
      weight for mothers and children and Mid-Upper Arm Circumference for young
      children) were taken using standard techniques. The body mass index of women was
      calculated. All nutritional indices were compared with reference standards. Food
      insecurity was assessed using the Household Hunger Scale and Dietary Diversity
      Score, then analysed using the Statistical Product for Service Solution version
      21. Data analysis used descriptive statistics. Most (91.2%) of the respondents
      were female. The matrilineal system known as ikwu nne or iri ala a nne
      (inheritance through mothers' lineage) is still in place but is changing. One
      important benefit of the system is the access to land by women. Whereas women
      participated actively in agriculture, food preparation, and care of family, the
      men were moving to off-farm activities. High prevalence of household food
      insecurity (66%) and signs of malnutrition including moderate to severe stunting
      (48.4%) and wasting (31.7%) in children, household hunger (34.5%), and overweight
      (27.5%) and obesity (19.2%) among mothers were observed. These communities
      urgently need gender sensitive food and nutrition interventions.

PMID- 29359438
TI  - Mothers' groups enrich diet and culture through promoting traditional Quichua
      foods.
AB  - Indigenous Peoples in Latin America bear a disproportionate burden of
      undernutrition, yet traditional foods, including wild leafy greens, can
      contribute nutritional value to diets. As part of a community nutrition
      intervention using local foods in highland Tungurahua, Ecuador, mothers' groups
      promoted the consumption of wild leafy greens through community cooking clubs and
      recipe competitions at local fairs. The objective was to assess the social,
      cultural, and nutritional potential of a mothers' club intervention that promoted
      2 indigenous greens (stinging nettle/Urtica dioica L. and round-leaved dock/Rumex
      obtusifolius L.) into children's diets. Key informant interviews and focus groups
      were conducted with 54 mothers and 16 elders to identify perceptions of the
      intervention and traditional foods. Social and cultural dimensions were
      identified through content analysis. The nutritional contribution of the leafy
      greens was estimated through semiquantitative food frequency questionnaires
      conducted with 160 participant mothers and 98 mothers living in comparison
      communities who had not been exposed to the intervention. The use of local foods
      generated pride for mothers and elders. Nonfood uses of the nettle proved an
      initial barrier to acceptance; however, peer support within mothers' groups
      enabled increased consumption. The greens were estimated to contribute an
      additional 8% vitamin A, 7% iron, 12% vitamin C, and 27% folate to children's
      recommended dietary intakes. By promoting wild leafy greens, mothers' groups
      improved food security and the cultural and nutritional value of their diets.
      Additionally, mothers' cooking clubs increased self-efficacy and cultural
      identity for Quichua women, offering a highly acceptable nutrition intervention
      model.

PMID- 29359437
TI  - Nutritional status, food insecurity, and biodiversity among the Khasi in
      Meghalaya, North-East India.
AB  - A community-based cross-sectional study was carried out with 603 children ages 5
      and under and 500 of their mothers from 510 households to examine the prevalence
      of undernutrition and chronic diseases among the Khasis of North-East India.
      Anthropometric measurements including Mid-Upper Arm Circumference, height, and
      weight were taken. Dry blood spots to estimate haemoglobin and vitamin A were
      collected from children and women separately by finger prick. Mothers provided
      data about household socio-demographic particulars and infant and young child
      feeding practices. The prevalence in children of underweight was 31%, stunting
      was 57%, and wasting was 10%. Undernutrition was higher among boys as compared to
      girls. Nutrient intakes were below recommended levels. The prevalence of anaemia
      among children ages 1 to 5 years old was 68%, and vitamin A deficiency was 59%,
      and they were 83% and 48%, respectively, among women. Hypertension was observed
      in 15% of women, whereas diabetes was less than 1%. Only about 20% of households
      were food secure, and this was associated with parental literacy, per capita
      income, and family size. Undernutrition was unacceptably high among the Khasis
      despite rich food biodiversity. Proper implementation of nutritional intervention
      programs such as Integrated Child Development Services, Mid Day Meal, and the
      Public Distribution System will improve the nutrient intake and nutritional
      status of the population. Additionally, preservation of forest lands and products
      paired with judicious use of the rich food biodiversity available will promote
      dietary diversity and ultimately better nutrition and health.

PMID- 29359439
TI  - Reclaiming food security in the Mohawk community of Kahnawa:ke through
      Haudenosaunee responsibilities.
AB  - Indigenous Peoples are reclaiming their food security, nutrition, and well-being
      by revitalizing food systems, livelihoods, knowledge-systems, and governance. Our
      food security research is guided by sustainable self-determination that focuses
      on restoring Indigenous cultural responsibilities and relationships to land, each
      other, and the natural world (Corntassel, 2008). Our Kanien'keha:ka (Mohawk)
      research team from Kahnawa:ke, in Quebec, Canada, examines food insecurity
      experiences in our community to explore ways of upholding our Haudenosaunee
      responsibilities and enhancing local food security. We collaboratively designed
      the study and interviewed Kahnawakehro:non (people from the Kahnawake community)
      with traditional knowledge, extensive community experience, and interests in food
      and culture. Interviews were audio-recorded, transcribed, and analysed by the
      team. Analysis characterized food insecurity experiences and conditions that
      challenge and enable food security with attention to traditional food systems,
      relationships to land, and gender-related responsibilities. Findings show that
      communal responsibilities generate resilient strategies that provide for all in
      times of crisis, and long-term food insecurity is managed through social
      programs, organized charities, and family support. Enhancing food security
      involves healing and protecting a limited land-base for food production,
      integrating food production with community priorities for education, training,
      health, economic development, and scientific innovation. Nurturing spiritual
      connections with tionhnhehkwen (life sustaining foods), the natural world, and
      each other calls for accelerated teaching and practicing our original
      instructions. Challenges in developing food security leadership, balancing
      capitalism and subsistence economies, and strengthening social relationships are
      rooted in the historical colonial and current settler-colonial context that
      disrupts all aspects of Kanien'keha:ka society.

PMID- 29359440
TI  - Foreword.

PMID- 29359441
TI  - Food security and women's roles in Moroccan Berber (Amazigh) society today.
AB  - Traditionally, the Berber diet was part of a semiautarkic economy. The
      suitability of the diet to the regional ecosystem has guaranteed food security
      for the Berber tribes of Morocco and other countries of North Africa. As part of
      a patriarchal model, Berber dietary patterns are historically embedded in a
      social system where women's and men's roles are complementary at all stages of
      food production, processing, and conservation. Women have played a dominant role
      in the conservation of Berber dietary patterns through the preservation of
      biodiverse seeds and local varieties, the transmission of the Berber language
      through generations, and the sharing of knowledge on food, medicinal plants, and
      cultural practices related to diet and food security. Political, social,
      demographic, economic, and cultural factors have affected the Berber dietary
      model and the role of women in its preservation. The shift from a semiautarkic
      traditional model to a model within a market economy has led to food importation,
      the erosion of culinary components such as wild edible plants and dietary
      homogenization. Despite these changes and the associated nutrition transition,
      the Berber diet remains a cultural heritage because of its rich diversity. Berber
      women play a crucial role in the preservation and sustainability of Berber
      culinary heritage and food security.

PMID- 29359442
TI  - Transmitting Ainu traditional food knowledge from mothers to their daughters.
AB  - Since 2004, research has been conducted in the Ainu Indigenous community of the
      Saru River Region of Biratori in Northern Japan examining traditional food use
      knowledge. The purpose was to improve the socio-cultural environment for the Ainu
      People by implementing interventions meant to reintroduce traditional Ainu food
      use, so that they can live with dignity and in harmony with non-Ainu people in
      the heterogeneous community where Japanese cultural values dominate. Ten years
      after the start of this research, a series of interviews was conducted with Ainu
      mothers and daughters active in the community to evaluate the result of the
      interventions because, in accordance with culturally established Ainu gender
      roles, the Ainu women prepare the Ainu dishes. The interviews indicated that the
      community of both Ainu and non-Ainu people shared traditional Ainu food as a
      communal food at community events organized by the Ainu members of the community.
      The people in the community now identify traditional Ainu dishes with Ainu names,
      indicating the establishment of culinary and linguistic boundaries between Ainu
      traditional food and mainstream Japanese food. This also signals that the Ainu
      People have begun to establish a basis for reconstructing their unique ethnic
      identity, once suppressed by the government's former assimilation policy.

PMID- 29359443
TI  - Preface.

PMID- 29359444
TI  - Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and
      endocrinological abnormalities.
AB  - MAGEL2 is the paternally expressed gene within Prader-Willi syndrome critical
      region at 15q11.2. We encountered three individuals in whom truncating mutations
      of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non
      consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe
      respiratory difficulty, poor feeding, and multiple anomalies including
      arthrogryposis soon after birth. We carried out whole-exome sequencing, which
      detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients'
      father was heterozygous for the mutation. Patient 3 was a female infant, showed
      respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia,
      feeding difficulty and multiple anomalies soon after birth. Targeted next
      generation sequencing detected a novel heterozygous mutation in MAGEL2
      (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2
      mutations, first reported to be the cause of the Prader-Willi like syndrome with
      autism by Schaaf et al. (2013) Nature Genetics, 45: 1405-1408 show the wide range
      of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism
      spectrum disorder (ASD) and mild intellectual disability (ID). Our results
      indicate that MAGEL2 mutations cause multiple congenital anomalies and
      intellectual disability accompanied by arthrogryposis multiplex congenita and
      various endocrinologic abnormalities, supporting that the view that clinical
      phenotypes of MAGEL2 mutations are variable.

PMID- 29359445
TI  - Not all choices are equal.

PMID- 29359446
TI  - Trends and uptake of new formulations of controlled-release oxycodone in Canada.
AB  - PURPOSE: This study investigated the impact of changing availability of tamper
      deterrent and non-tamper-deterrent oxycodone on prescribing patterns of
      controlled-release oxycodone across Canada. METHODS: We conducted a population
      based, serial cross-sectional study of controlled-release oxycodone dispensing
      from community pharmacies across Canada between October 2007 and April 2016. We
      calculated rates of dispensing (tablets per 100 population) and reported the
      relative market share of generic non-tamper-deterrent controlled-release
      oxycodone. All analyses were reported nationally and stratified by province.
      RESULTS: After the introduction of a tamper-deterrent formulation, the national
      rate of controlled-release oxycodone dispensing fell by 44.6% (from 26.4 to 14.6
      tablets per 100 population from February 2012 to April 2016). Between December
      2012 and July 2013, there was moderate uptake of generic non-tamper-deterrent
      controlled-release oxycodone (968 452 tablets; 16.0% in July 2013), which
      appeared to have little impact on the overall rate of controlled-release
      oxycodone dispensing in Canada. However, the uptake of generic non-tamper
      deterrent oxycodone varied considerably by province. By April 2016, 55.0% of all
      controlled-release oxycodone tablets dispensed in Quebec were for the generic
      formulation. Elsewhere in Canada, this prevalence was less than 30%, ranging
      between 1.6% (Prince Edward Island) and 26.9% (British Columbia) at the end of
      our study period. CONCLUSIONS: The changing availability of tamper-deterrent and
      non-tamper-deterrent formulations of controlled-release oxycodone in Canada has
      had variable influence on the rate of use of these products across Canada. Future
      research should explore whether the availability of generic controlled-release
      oxycodone has led to measurable changes in the safety of oxycodone use in Canada.

PMID- 29359447
TI  - Does distance to a cystic fibrosis center impact health outcomes?
AB  - INTRODUCTION: This paper considers the impact of geographic distance from cystic
      fibrosis centers on lung function in children, young adults, and adults with
      cystic fibrosis. METHODS: Clinical patient-level data on 20 351 patients from
      1986 to 2011 were evaluated from the Cystic Fibrosis Foundation National Patient
      Registry. We measure distance using a patient's zip code centroid to the center
      where they received care. A heteroscedastic mixed effects model was used to
      capture the association of distance with longitudinal variation in patients' lung
      function. RESULTS: Children, young adults, and adults in lower socioeconomic
      categories had a %FEV1 between 3 and 10 percentage-points lower than those living
      in higher income areas and those privately insured. For patients who changed
      distance categories, high distance was associated with lower lung function in
      young adults (P-value <0.001). For older patients we observed the reverse,
      suggesting that the choice to move farther away is associated with better health
      (P-value <0.001). For patients who did not change distance categories, only
      medium distance in children was significant (P-value = 0.01). Known confounding
      factors including age and CFTR mutation class were statistically significantly
      associated to health outcomes (P-value <0.001). CONCLUSIONS: This study shows
      distance is not found to be associated with health lung function among patients
      whose distance category remained unchanged during the analysis. For patients who
      move, the association of health with distance depends on the age of the patient;
      adult patients further from their care center are healthier. Overall, we find
      that socioeconomic and genetic factors appear to impact health outcomes to a
      greater extent.

PMID- 29359448
TI  - Targeted gene panel sequencing prenatally detects two novel mutations of DYNC2H1
      in a fetus with increased biparietal diameter and polyhydramnios.
AB  - BACKGROUND: Genetic skeletal disorders (GSDs) are clinically and genetically
      heterogeneous with more than 350 genes accounting for the diversity of disease
      phenotypes. Prenatal diagnosis of these disorders has been challenging because of
      the limited but variable prenatal phenotypes, highlighting the need of a novel
      genetic approach. Short-rib polydactyly syndrome (SRPS) Type III is an autosomal
      recessive GSD characterized by extreme narrowness of the thorax, severely
      shortened tubular bones, polydactyly and multiple malformations. METHODS:
      Cytogenetic and molecular analyses using GTG-banding, single nucleotide
      polymorphism array and a novel GSDs targeted gene panel sequencing were performed
      in a 24 weeks fetus with increased biparietal diameter (BPD), short limbs, narrow
      thorax and polyhydramnios. RESULTS: No chromosomal abnormalities and pathogenic
      copy number variations (CNVs) were detected in the fetus. Two novel compound
      heterozygous mutations c.2992C > T and c.12836G > C in the DYNC2H1 gene were
      identified by targeted genes panel sequencing. A literature review was performed
      to delineate the prenatal phenotype of SRPS Type III. CONCLUSION: This is the
      first report of prenatal diagnosis of DYNC2H1 mutations causing SRPS Type III in
      a fetus with increased BPD associated with polyhydramnios in China. Our findings
      expand the mutation spectrum of DYNC2H1 in this rare disease and demonstrate that
      targeted gene panel capture followed by next-generation sequencing (NGS) is an
      efficient and cost-effective method to perform a molecular prenatal diagnosis of
      a rare genetic skeletal disorder.

PMID- 29359449
TI  - PTEN mutation in a Japanese boy with autonomously functioning thyroid nodule.

PMID- 29359450
TI  - A multi-source adaptive platform design for testing sequential combinatorial
      therapeutic strategies.
AB  - Traditional paradigms for clinical translation are challenged in settings where
      multiple contemporaneous therapeutic strategies have been identified as
      potentially beneficial. Platform trials have emerged as an approach for
      sequentially comparing multiple trials using a single protocol. The Ebola virus
      disease outbreak in West Africa represents one recent example which utilized a
      platform design. Specifically, the PREVAIL II master protocol sequentially tested
      new combinations of therapies against the concurrent, optimal standard of care
      (oSOC) strategy. Once a treatment demonstrated sufficient evidence of benefit,
      the treatment was added to the oSOC for all future comparisons (denoted as
      segments throughout the manuscript). In the interest of avoiding bias stemming
      from population drift, PREVAIL II considered only within-segment comparisons
      between the oSOC and novel treatments and failed to leverage data from oSOC
      patients in prior segments. This article describes adaptive design methodology
      aimed at boosting statistical power through Bayesian modeling and adaptive
      randomization. Specifically, the design uses multi-source exchangeability models
      to combine data from multiple segments and adaptive randomization to achieve
      information balance within a segment. When compared to the PREVAIL II design, we
      demonstrate that our proposed adaptive platform design improves power by as much
      as 51% with limited type-I error inflation. Further, the adaptive platform
      effectuates more balance with respect to the distribution of acquired information
      among study arms, with more patients randomized to experimental regimens.

PMID- 29359451
TI  - The spleen of patients with myelofibrosis harbors defective mesenchymal stromal
      cells.
AB  - Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In
      fact, the spleen of patients with MF contains malignant hematopoietic stem cells
      retaining a complete differentiation program, suggesting both a pivotal role of
      the spleen in maintaining the disease and a tight regulation of hematopoiesis by
      the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs).
      Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological
      context. In this work, we have in vitro expanded and characterized Sp-MSCs from
      25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype,
      growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed
      significant lower levels of nestin, and favored megakaryocyte (Mk)
      differentiation in vitro at a larger extent than their normal counterpart.
      Moreover, they showed a significant upregulation of matrix metalloprotease 2
      (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein
      level, and, finally, developed genetic abnormalities which were never detected in
      HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic
      niche in patients with MF that could be responsible of some pathological features
      of the disease, including the increased trafficking of CD34+ cells and the
      expansion of the megakaryocytic lineage.

PMID- 29359452
TI  - Prevalence, Presentation and Treatment of 'Balloon Undilatable' Chronic Total
      Occlusions: Insights from a Multicenter US Registry.
AB  - BACKGROUND: The prevalence, treatment and outcomes of balloon undilatable chronic
      total occlusions (CTOs) have received limited study. METHODS: We examined the
      prevalence, clinical and angiographic characteristics, and procedural outcomes of
      percutaneous coronary interventions (PCIs) for balloon undilatable CTOs in a
      contemporary multicenter US registry. RESULTS: Between 2012 and 2017 data on
      balloon undilatable lesions were available for 425 consecutive CTO PCIs in 415
      patients in whom guidewire crossing was successful: 52 of 425 CTOs were balloon
      undilatable (12%). Mean patient age was 65 +/- 10 years and most patients were
      men (84%). Patients with balloon undilatable CTOs were more likely to be diabetic
      (67 vs. 41%, P < 0.001) and have heart failure (44 vs. 28%, P = 0.027). Balloon
      undilatable CTOs were longer (40 mm [interquartile range, IQR 20-50] vs. 30 [IQR
      15-40], P = 0.016), more likely to have moderate/severe calcification (87 vs.
      54%, P < 0.001), and had higher J-CTO score (3.2 +/- 1.1 vs. 2.5 +/- 1.3, P <
      0.001) and PROGRESS-CTO complications score (3.9 +/- 1.7 vs. 3.1 +/- 2.0, P <
      0.005). They were associated with lower technical and procedural success (92 vs.
      98%, P = 0.024; and 88 vs. 96%, P = 0.034, respectively) and higher risk for in
      hospital major adverse events (8 vs. 2%, P = 0.008) due to higher perforation
      rates. The most frequent treatments for balloon undilatable CTOs were high
      pressure balloon inflations (64%), rotational atherectomy (31%), laser (21%), and
      cutting balloons (15%). CONCLUSIONS: Balloon undilatable CTOs are common and are
      associated with lower success and higher complication rates.

PMID- 29359453
TI  - Strong xenoprotective function by single-copy transgenes placed sequentially at a
      permissive locus.
AB  - BACKGROUND: Multiple xenoprotective transgenes are best grouped at a single locus
      to avoid segregation during breeding and simplify production of donor animals.
      METHODS: We used transgene stacking to place a human CD55 transgene adjacent to a
      human heme oxygenase 1 construct at the porcine ROSA26 locus. A transgenic pig
      was analyzed by PCR, RT-PCR, droplet digital PCR, immunohistochemistry,
      immunofluorescence, and flow cytometry. Resistance to complement-mediated cell
      lysis and caspase 3/7 activation were determined in vitro. RESULTS: The ROSA26
      locus was retargeted efficiently, and animals were generated by nuclear transfer.
      RNA and protein analyses revealed abundant expression in all organs analyzed,
      including pancreatic beta cells. Transgenic porcine kidney fibroblasts were
      almost completely protected against complement-mediated lysis and showed reduced
      caspase 3/7 activation. CONCLUSION: Step-by-step placement enables highly
      expressed single-copy xenoprotective transgenes to be grouped at porcine ROSA26.

PMID- 29359454
TI  - Repeatability and Reproducibility of the Ultrasonic Attenuation Coefficient and
      Backscatter Coefficient Measured in the Right Lobe of the Liver in Adults With
      Known or Suspected Nonalcoholic Fatty Liver Disease.
AB  - OBJECTIVES: To assess the repeatability and reproducibility of the ultrasonic
      attenuation coefficient (AC) and backscatter coefficient (BSC) measured in the
      livers of adults with known or suspected nonalcoholic fatty liver disease
      (NAFLD). METHODS: The Institutional Review Board approved this Health Insurance
      Portability and Accountability Act-compliant prospective study; informed consent
      was obtained. Forty-one research participants with known or suspected NAFLD were
      recruited and underwent same-day ultrasound examinations of the right liver lobe
      with a clinical scanner by a clinical sonographer. Each participant underwent 2
      scanning trials, with participant repositioning between trials. Two transducers
      were used in each trial. For each transducer, machine settings were optimized by
      the sonographer but then kept constant while 3 data acquisitions were obtained
      from the liver without participant repositioning and then from an external
      calibrated phantom. Raw RF echo data were recorded. The AC and BSC were measured
      within 2.6 to 3.0 MHz from a user-defined hepatic field of interest from each
      acquisition. The repeatability and reproducibility were analyzed by random
      effects models. RESULTS: The mean AC and log-transformed BSC (logBSC) were 0.94
      dB/cm-MHz and -27.0 dB, respectively. Intraclass correlation coefficients were
      0.88 to 0.94 for the AC and 0.87 to 0.95 for the logBSC acquired without
      participant repositioning. For between-trial repeated scans with participant
      repositioning, the intraclass correlation coefficients were 0.80 to 0.84 for the
      AC and 0.69 to 0.82 for the logBSC after averaging results from 3 within-trial
      images. The variability introduced by the transducer was less than the
      repeatability error. CONCLUSIONS: Hepatic AC and BSC measures using a reference
      phantom technique on a clinical scanner are repeatable and reproducible between
      transducers in adults with known or suspected NAFLD.

PMID- 29359455
TI  - Ancient and recent Middle Eastern maternal genetic contribution to North Africa
      as viewed by mtDNA diversity in Tunisian Arab populations.
AB  - OBJECTIVES: Through previous mitochondrial DNA studies, the Middle Eastern
      maternal genetic contribution to Tunisian populations appears limited. In fact,
      most of the studied communities were cosmopolitan, or of Berber or Andalusian
      origin. To provide genetic evidence for the actual contribution of Middle Eastern
      mtDNA lineages to Tunisia, we focused on two Arab speaking populations from
      Kairouan and Wesletia known to belong to an Arab genealogical lineage. MATERIALS
      AND METHODS: A total of 114 samples were sequenced for the mtDNA HVS-I and HVS-II
      regions. Using these data, we evaluated the distribution of Middle Eastern
      haplogroups in the study populations, constructed interpolation maps, and
      established phylogenetic networks allowing estimation of the coalescence time for
      three specific Middle Eastern subclades (R0a, J1b, and T1). RESULTS: Both studied
      populations displayed North African genetic structure and Middle Eastern lineages
      with a frequency of 12% and 28.12% in Kairouan and Wesletia, respectively. TMRCA
      estimates for haplogroups T1a, R0a, and J1b in Tunisian Arabian samples were
      around 15 000 YBP, 9000 to 5000 YBP, and 960 to 600 YBP, respectively.
      CONCLUSIONS: The Middle Eastern maternal genetic contribution to Tunisian
      populations, as to other North African populations, occurred mostly in deep
      prehistory. They were brought in different migration waves during the Upper
      Paleolithic, probably with the expansion of Iberomaurusian culture, and during
      Epipaleolithic and Early Neolithic periods, which are concomitant with the
      Capsian civilization. Middle Eastern lineages also came to Tunisia during the
      recent Islamic expansion of the 7th CE and the subsequent massive Bedouin
      migration during the 11th CE.

PMID- 29359456
TI  - The Nature and Consequences of Essentialist Beliefs About Race in Early
      Childhood.
AB  - It is widely believed that race divides the world into biologically distinct
      kinds of people-an essentialist belief inconsistent with reality. Essentialist
      views of race have been described as early emerging, but this study found that
      young children (n = 203, Mage  = 5.45) hold only the more limited belief that the
      physical feature of skin color is inherited and stable. Overall, children
      rejected the causal essentialist view that behavioral and psychological
      characteristics are constrained by an inherited racial essence. Although average
      levels of children's causal essentialist beliefs about race were low, variation
      in these beliefs was related to children's own group membership, exposure to
      diversity, as well as children's own social attitudes.

PMID- 29359457
TI  - The levonorgestrel-releasing intrauterine system is associated with a reduction
      in dysmenorrhoea and dyspareunia, a decrease in CA 125 levels, and an increase in
      quality of life in women with suspected endometriosis.
AB  - BACKGROUND AND AIMS: The aim of this study was to investigate the effectiveness
      of a levonorgestrel-releasing intrauterine device (LNG-IUS) in the symptomatic
      relief of pain in women with endometriosis and additionally, to assess the
      changes in women's life quality and serum cancer antigen (CA) 125 levels.
      MATERIALS AND METHODS: All women who had an LNG-IUS inserted for the treatment of
      dysmenorrhea, chronic pelvic pain or both for more than six months over a two
      year period were included in the study. Each woman was asked to complete
      questionnaires of the Short Form-36 and visual analogue scales (VAS) in the first
      visit and the third, sixth, ninth and twelfth months after the LNG-IUS insertion.
      CA 125 levels were measured at each visit. RESULTS: Forty-five women were
      included in the study. At the end of 12 months, mean dysmenorrhoea VAS score
      decreased from 6.13 to 2.88, mean dsyspareunia VAS score from 6.04 to 2.61 and CA
      125 level from 50.67 to 22.45. Endometriomas reduced in size in six women (mean
      size decreased from 31 to 20 mm) and disappeared in three. CONCLUSIONS: Several
      favourable outcomes were found following LNG-IUS insertion: (i) dyspareunia and
      dysmenorrhoea were clearly reduced; (ii) the size of endometriomas were
      decreased; (iii) CA 125 levels significantly decreased; (iv) a few women
      experienced the typical systemic adverse effects of progestogens; however, LNG
      IUS-related adverse events were generally tolerable and the discontinuation rate
      was as low as 6.66% (3/45).

PMID- 29359458
TI  - Dose-dependent relationships between weight status and clinical outcomes among
      infants hospitalized with respiratory syncytial virus infections.
AB  - BACKGROUND: Associations between weight status and manifestations of respiratory
      syncytial virus infections remain unclear, especially in infants. OBJECTIVE: This
      study investigated the dose-response relationships between weight status and
      clinical outcomes among infants hospitalized with respiratory syncytial virus
      infections. METHODS: We obtained hospital discharge records for inpatients aged
      <12 months with diagnoses of bronchitis/pneumonia and respiratory syncytial virus
      infections, using a Japanese national inpatient database. The patients were
      classified into underweight, normal-weight, or overweight/obese groups using
      weight-for-length according to World Health Organization criteria. We compared
      need for intensive care, 30-day readmission, mean total hospitalization costs,
      and length of hospital stay across the three groups using multivariable mixed
      effects regression models and restricted cubic spline functions. RESULTS:
      Overall, 42 698 patients were identified, comprising 3697 underweight, 35 849
      normal-weight, 3152 overweight/obese patients. The underweight group had
      significantly higher risk of intensive care (adjusted odds ratio, 1.35; 95%
      confidence interval, 1.18-1.82) and longer length of stay (adjusted difference,
      0.12 days; 95% confidence interval, 0.04-0.20 days) than the normal-weight group.
      No significant differences in 30-day readmission or hospitalization costs were
      observed among the three groups. The lower and upper thresholds for a significant
      association between weight status and intensive care were weight-for-length z
      scores of -0.64 (26th percentile) and 2.08 (98th percentile), respectively.
      CONCLUSIONS: These findings demonstrate that abnormal weight status is an
      independent risk factor for greater illness severity among infants hospitalized
      with respiratory syncytial virus infections.

PMID- 29359459
TI  - Distinct effect of age, sex, and CMV seropositivity on dendritic cells and
      monocytes in human blood.
AB  - We analyzed the impact of age, sex, and CMV on blood monocyte and dendritic cell
      (DC) subpopulations in 256 healthy individuals aged from 19 to 96 years. Flow
      cytometry was performed on whole blood within the 4 h following blood drawing.
      Myeloid (mDC) and plasmacytoid DC (pDC), classical, intermediate, and
      nonclassical monocytes were enumerated by means of TruCount tubes (BD
      Biosciences). We provided reference values for mDC, pDC and the three monocyte
      subpopulations. The numbers of classical, intermediate, and nonclassical
      monocytes slightly increased with age while the numbers of mDC and pDC did not
      vary significantly. The level of expression of CD64 and CD163 on monocytes
      significantly increased with age while HLA-DR expression did not vary
      significantly. More precisely, CD163 expression level on intermediate monocyte
      slightly increased with age in women only (Spearman P = 0.019) while CD64
      expression increased on monocytes in CMV-positive individuals only. We observed
      that sex had almost no impact on the numbers of monocytes and DC and on their
      expression level of CD64 and HLA-DR. We observed a significant decrease in the
      numbers of pDC with age in CMV-positive individuals, but not in CMV negative
      individuals. This suggests that the lifelong subclinical infection by CMV could
      influence the number of circulating DC of lymphoid origin. In contrast, CMV
      serostatus had no significant impact on absolute numbers of mDC and monocytes.

PMID- 29359460
TI  - Resolution of methylphenidate osmotic release oral system-induced hair loss in
      two siblings after dose escalation.
AB  - This report describes the cases of two siblings who experienced hair loss after
      treatment with methylphenidate (MPH) osmotic release oral system (OROS). Hair
      loss was resolved after discontinuation of the drug, but the children re
      initiated treatment, after which hair loss again occurred, but they continued the
      treatment. After dose escalation, the hair loss resolved. This is the first
      report to describe resolution of OROS-MPH-induced hair loss after dose
      escalation.

PMID- 29359462
TI  - Automatic detection of multisize pulmonary nodules in CT images: Large-scale
      validation of the false-positive reduction step.
AB  - PURPOSE: Currently reported computer-aided detection (CAD) approaches face
      difficulties in identifying the diverse pulmonary nodules in thoracic computed
      tomography (CT) images, especially in heterogeneous datasets. We present a novel
      CAD system specifically designed to identify multisize nodule candidates in
      multiple heterogeneous datasets. METHODS: The proposed CAD scheme is divided into
      two phases: primary phase and final phase. The primary phase started with the
      lung segmentation algorithm and the segmented lungs were further refined using
      morphological closing process to include the pleural nodules. Next, we
      empirically formulated three subalgorithms modules to detect different sizes of
      nodule candidates (>=3 and <6 mm; >=6 and <10 mm; and >=10 mm). Each subalgorithm
      module included a multistage flow of rule-based thresholding and morphological
      processes. In the final phase, the nodule candidates were augmented to boost the
      performance of the classifier. The CAD system was trained using a total number of
      nodule candidates = 201,654 (after augmentation) and nonnodule candidates =
      731,486. A rich set of 515 features based on cluster, texture, and voxel-based
      intensity features were utilized to train a neural network classifier. The
      proposed method was trained on 899 scans from the Lung Image Database
      Consortium/Image Database Resource Initiative (LIDC-IDRI). The CAD system was
      also independently tested on 153 CT scans taken from the AAPM-SPIE-LungX Dataset
      and two subsets from the Early Lung Cancer Action Project (ELCAP and PCF).
      RESULTS: For the LIDC-IDRI training set, the proposed CAD scheme yielded an
      overall sensitivity of 85.6% (1189/1390) and 83.5% (1161/1390) at 8 FP/scan and 1
      FP/scan, respectively. For the three independent test sets, the CAD system
      achieved an average sensitivity of 68.4% at 8 FP/scan. CONCLUSION: The authors
      conclude that the proposed CAD system can identify dissimilar nodule candidates
      in the multiple heterogeneous datasets. It could be considered as a useful tool
      to support radiologists during screening trials.

PMID- 29359463
TI  - Curiosity and Science.
AB  - Using curiosity as the starting point for careful observation of nature and
      society is a nontrivial skill, and a starting point for new intellectual
      endeavors and adventures. It is one essential contributor to creativity in
      science, and a start in forcing new ideas into inflexible professional
      orthodoxies.

PMID- 29359461
TI  - Risk factors for 30-day complications after cancer surgery in geriatric patients:
      a secondary analysis.
AB  - BACKGROUND: The aim was to analyse the association between severity of
      complications up to 30 days after surgery and pre-operative nutritional and
      physical performance parameters. METHODS: The participants were a subsample of
      the previously published PERATECS study (ClinicalTrials.gov: NCT01278537) and
      included 517 onco-geriatric patients aged >= 65 years, undergoing
      thoracoabdominal, gynaecological, or urological surgery. Post-operative
      complications were classified according to the Clavien Classification System
      (CCS). Independent risk factors related to the severity of complications, defined
      as major complications (CCS IIIa-V) and graded complications (CCS grade 0-V),
      were analysed using logistic and ordinal regression, respectively. RESULTS: In
      total, 132 patients suffered major post-operative complications. The development
      of major post-operative complications was independently associated with body mass
      index (BMI) < 20 kg/m2 , hypoalbuminaemia (< 30 g/l), longer duration of surgery,
      and specific tumour sites (upper gastrointestinal, gynaecological, colorectal)
      (all P < 0.05). Higher-grade complications were predicted by Timed Up and Go
      (TUG) > 20 s, hypoalbuminaemia (< 30 g/l), higher American Society of
      Anesthesiologists (ASA) status III-IV, longer duration of surgery (> 165 min),
      and specific tumour sites (upper gastrointestinal, gynaecological) (all P <
      0.05). Mini Nutritional Assessment (MNA) scores and weight loss were not
      independent risk factors for the severity of complications. CONCLUSIONS:
      Nutritional and physical performance risk factors that predicted the severity of
      complications differed between major and higher-grade post-operative
      complications, but hypoalbuminaemia independently predicted both. The results
      support the need for pre-operative risk screening. Due to the explorative nature
      of the study, further research is required in larger cohorts to corroborate these
      findings.

PMID- 29359464
TI  - A prospective analysis for prevalence of complications in Thai nontransfusion
      dependent Hb E/beta-thalassemia and alpha-thalassemia (Hb H disease).
AB  - Recently, complications in patients with nontransfusion-dependent thalassemia
      (NTDT), in particular those with beta-thalassemia intermedia (beta-TI), were
      found to be significantly different from those in patients with transfusion
      dependent thalassemia (TDT), mainly beta-thalassemia major (beta-TM). However,
      this information is rather limited in other forms of NTDT. In this prospective
      study, adult Thai NTDT patients were interviewed and clinically evaluated for
      thalassemia related complications. Fifty-seven NTDT patients (age 18-74 years),
      59.6% Hb E/beta-thalassemia and 40.4% Hb H disease, were recruited; 26.4% were
      splenectomized. The most common complications were gallstones (68.4%),
      osteoporosis (26.3%), and pulmonary hypertension (15.8%). Splenectomy was
      associated with higher rate of gallstones and serious infection (P = .001 and
      .052, respectively), consistent with a multivariate analysis (RR = 9.5, P = .044,
      and RR = 15.1, P = .043, respectively). In addition, a higher hemoglobin level
      was inversely associated with gallstones in both univariate and multivariate
      analyses (P = .01 and .022, respectively). Serum ferritin was associated with
      abnormal liver function (P = .002). In contrast to the previous study, the
      prevalence of thrombosis was less common in our population (1.7%), probably due
      to differences in transfusion therapy, ethnicity, and underlying genotypes. For
      the first time, this prospective study provided the current prevalence of NTDT
      related complications in a Southeast Asian population with a different underlying
      genetic basis compared with previous studies. Although individual prevalence of
      each complication might differ from other studies, several important clinical
      factors such as splenectomy, degree of anemia, and iron overload seem to be
      determining risks of developing these complications consistently across different
      ethnicities.

PMID- 29359465
TI  - An efficient scheme for purification of a novel recombinant immunotoxin,
      rCCK8PE38, for anti-tumour experiments.
AB  - rCCK8PE38 is a novel immunotoxin that targets choleystokinin B receptor, which is
      over-expressed in some tumor tissues. Although we constructed a prokaryotic
      expression vector to express rCCK8PE38 in our laboratory, thorough purification
      was necessary to quantitatively assess its anti-tumor effect. In this study, we
      established a purification protocol to obtain rCCK8PE38 with high purity from E.
      coli. Three different types of chromatography, hydrophobic chromatography, ion
      exchange chromatography and size exclusion chromatography, were used in
      combination. The purification technological parameters of each chromatography
      type were optimized. The whole process of purification was arranged to minimize
      the purification steps and achieve purity and bioactivity. Finally, through this
      optimized scheme, we obtained a recombinant protein with a purity of >95%; then,
      the protein was stored at -80 degrees C after lyophilization. The purified
      protein was used in a tumor inhibition experiment and was effective in killing
      tumor cells that over-expressed choleystokinin B receptor. The results of this
      study may provide some valuable information about protein purification and lay
      the foundation for further clinical experiments with rCCK8PE38.

PMID- 29359466
TI  - Wnt/beta-Catenin/TCF Pathway Is a Phase-Dependent Promoter of Colony Formation
      and Mesendodermal Differentiation During Human Somatic Cell Reprogramming.
AB  - Somatic cell reprogramming is a biphasic phenomenon that goes through a
      mesenchymal-to-epithelial transition, called initiation phase, followed by a
      maturation phase wherein reprogramming cells acquire pluripotency. Here, we show
      that these phases display a differential response to Wnt signaling activation.
      Wnt signaling increases colony formation by promoting cellular epithelialization
      during the initiation phase in a TCF7-dependent manner. However, during
      maturation phase, it is also responsible for inducing mesendodermal
      differentiation, which is negatively regulated by TCF7L1. Thus, Wnt signaling
      inhibition or TCF7L1 overexpression downregulates mesendodermal gene expression
      without perturbing pluripotency. Together, our results demonstrate that a phase
      specific modulation of Wnt signaling leads to an improved reprogramming
      efficiency in terms of colony output and pluripotency acquisition. This work
      provides new insights into the cell context-dependent roles of Wnt signaling
      during human somatic cell reprogramming. Stem Cells 2018;36:683-695.

PMID- 29359467
TI  - Is side branch lesion length an independent predictor of acute side branch
      occlusion in provisional strategy? Analysis of 524 consecutive bifurcation
      lesions.
AB  - OBJECTIVES: To detect the impact of side branch (SB) lesion length on acute SB
      occlusion after main vessel (MV) stenting. METHODS: Five hundred sixteen
      consecutive patients with 524 bifurcation lesions undergoing one-stent techniques
      were studied. Multivariate logistic regression analysis was performed to identify
      independent predictors of acute SB occlusion. The lesions were also further
      divided into two groups according to the median SB lesion length. The incidences
      of SB occlusion and lesion characteristics in the two subgroups were compared.
      RESULTS: The SB lesion length was not significantly different between lesions
      with and without SB occlusion. In the SB occlusion group, the distance between
      the position of the minimal lumen diameter and SB ostium was significantly
      shorter than that in the non-SB occlusion group (1.76 +/- 1.04 mm vs. 2.72 +/-
      2.65 mm; P = 0.0003). Multivariate logistic regression analysis showed that high
      BA before stenting, plaque accumulation located on the same side as the SB, the
      Thrombolysis In Myocardial Infarction (TIMI) flow grade of the SB before
      stenting, and the DS of the SB before MV stenting were independently predictive
      of SB occlusion. CONCLUSIONS: SB lesion length cannot be regarded as an
      independent predictor of acute SB occlusion after MV stenting.

PMID- 29359468
TI  - A Neonatologist's Perspective: Is the Quest for an "Ideal" Lipid Emulsion Over?

PMID- 29359470
TI  - Shining LIGHT on the metabolic role of the cytokine TNFSF14 and the implications
      on hepatic IL-6 production.
AB  - The cytokine Tumor Necrosis Factor Superfamily member 14, TNFSF14 (or LIGHT), is
      a controversial player in numerous diseases. We investigated the role of
      endogenously expressed TNFSF14 in diet-induced obesity in vivo. Firstly, we
      studied the effects of Tnfsf14 ablation on the development of obesity, glucose
      intolerance, insulin resistance, steatosis, tissue inflammation, and
      mitochondrial respiration in the liver. Secondly, we examined the role of TNFSF14
      expression in hematopoietic cells on obesity and insulin sensitivity. Male
      Tnfsf14 knockout (KO) and wild type mice were fed chow or high fat diet (HFD) for
      12 weeks and were assessed for weight gain, glucose intolerance, insulin
      resistance, hepatosteatosis, mitochondrial dysfunction, and cytokine expression.
      Wild-type mice were also reconstituted with bone marrow cells from Tnfsf14
      knockout mice and were fed chow or HFD for 12 weeks. These mice were examined for
      weight gain and insulin resistance. HFD fed mice had elevated circulating levels
      of serum TNFSF14. Liver and white adipose tissue are potential sources of this
      elevated TNFSF14. Tnfsf14 deficient mice displayed increased obesity, glucose
      intolerance, insulin resistance, hepatosteatosis, and mitochondrial dysfunction
      compared to control mice on a HFD. Hepatic cytokine profiling pointed to a
      potential novel role of decreased IL-6 in the metabolic disturbances in
      obesogenic Tnfsf14 knockout mice. Bone marrow cells from Tnfsf14 deficient mice
      appeared to promote diet-induced obesity, insulin resistance and reduced FGF21
      levels in white adipose tissue and liver. Our novel data suggest that Tnfsf14
      ablation exacerbates parameters of the metabolic syndrome under high fat feeding
      conditions and provides evidence to support the development of TNFSF14 agonists
      as potential therapeutics in diet-induced obesity.

PMID- 29359471
TI  - A high plasma: red blood cell transfusion ratio during liver transplantation is
      associated with decreased blood utilization.
AB  - BACKGROUND: During massive transfusion, the volume ratio of administered plasma
      (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood
      utilization and improved survival. The aim of this study was to evaluate the
      optimal component ratio in the setting of liver transplantation. METHODS: This is
      a retrospective chart review of patients who underwent liver transplantation and
      received at least 500 ml of red blood cells from January 2013 through December
      2015. Kernel smoothing analysis determined the proper component ratios to
      evaluate were a >=0.85:1 ratio (high) to a <=0.85:1 ratio (low). Two groups,
      plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet
      units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were
      used to evaluate the component ratios. RESULTS: A total of 188 patients were
      included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed
      that 1238 ml (977-1653 ml) (P < 0.0001) and 1178 ml (747-1178) (P < 0.0001) of
      RBC were used in excess compared to the high ratio, in the univariable and
      multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a
      low ratio used 734 ml (193-1275) (P = 0.008) and 886 ml (431-1340) (P < 0.0001)
      of RBC in excess when compared to high ratio in the univariable and multivariable
      analysis, respectively. CONCLUSION: In patients undergoing liver transplantation,
      the transfusion of plasma to RBC ratio >=0.85 was associated with decreased need
      of RBC transfusions.

PMID- 29359469
TI  - P- and E-selectin receptor antagonism prevents human leukocyte adhesion to
      activated porcine endothelial monolayers and attenuates porcine endothelial
      damage.
AB  - BACKGROUND: Alongside the need to develop more effective and less toxic
      immunosuppression, the shortage of human organs available for organ
      transplantation is one of the major hurdles facing the field. Research into
      xenotransplantation, as an alternative source of organs, has unveiled formidable
      challenges. Porcine lungs perfused with human blood rapidly sequester the
      majority of circulating neutrophils and platelets, which leads to inflammation
      and organ failure within hours, and is not significantly attenuated by genetic
      modifications to the pig targeted to diminish antibody binding and complement and
      coagulation cascade activation. METHODS: Here, we model the interaction of
      freshly isolated human leukocytes with xenotransplanted vasculature under
      physiologic flow conditions using microfluidic channels coated with porcine
      endothelial cells. Both isolated human neutrophils and whole human blood were
      perfused over transgenic pig aortic endothelial cells that had been activated
      with rhTNF-alpha or rhIL-4 using the BioFlux system. Novel compounds GMI-1271 and
      rPSGL1.Fc were tested as E- and P- selectin antagonists, respectively. Cellular
      adhesion and rolling events were tracked using FIJI (imageJ). RESULTS: Porcine
      endothelium activated with either rhTNF-alpha or rhIL-4 expressed high amounts of
      selectins, to which isolated human neutrophils readily rolled and tethered. Both
      E-and P-selectin antagonism significantly reduced the number of neutrophils
      rolling and rolling distance in a dose-dependent manner, with near total
      inhibition at higher doses (P < .001). Similarly, with whole human blood,
      selectin blocking compounds exhibited dose-dependent inhibition of prevalent
      leukocyte adhesion and severe endothelial injury (Untreated: 394 +/- 97 PMNs/hpf,
      57 +/- 6% loss EC; GMI1271+rPSGL1.Fc: 23 +/- 9 PMNs/hpf, 8 +/- 6% loss EC P <
      .01). CONCLUSIONS: Selectin blockade may be useful as part of an integrated
      strategy to prevent neutrophil-mediated organ xenograft injury, especially during
      the early time points following reperfusion.

PMID- 29359473
TI  - Impacts of Adolescent and Young Adult Civic Engagement on Health and
      Socioeconomic Status in Adulthood.
AB  - The present study examines links between civic engagement (voting, volunteering,
      and activism) during late adolescence and early adulthood, and socioeconomic
      status and mental and physical health in adulthood. Using nationally
      representative data from the National Longitudinal Study of Adolescent to Adult
      Health, a propensity score matching approach is used to rigorously estimate how
      civic engagement is associated with outcomes among 9,471 adolescents and young
      adults (baseline Mage  = 15.9). All forms of civic engagement are positively
      associated with subsequent income and education level. Volunteering and voting
      are favorably associated with subsequent mental health and health behaviors, and
      activism is associated with more health-risk behaviors and not associated with
      mental health. Civic engagement is not associated with physical health.

PMID- 29359472
TI  - Silencing GRAS2 reduces fruit weight in tomato.
AB  - GRAS family transcription factors are involved in multiple biological processes
      in plants. Here, we report that GRAS2 plays a vital role in regulating fruit
      weight in tomato (Solanum lycopersicum). We establish that the expression of
      GRAS2 was elevated in ovaries and maintained at a constant level in fertilized
      ovules. Reduction of GRAS2 expression in transgenic plants reduced fruit weight
      through modulating ovary growth and cell size. At the metabolic level,
      downregulation of GRAS2 decreased activities of the gibberellic acid biosynthesis
      and signal transduction pathways, leading to insufficient levels of active
      gibberellic acid during the initial ovary development of tomato. Moreover,
      genotypic diversity of GRAS2 was consistent with the molecular basis of fruit
      weight evolution, suggesting that GRAS2 contributes to the molecular basis of the
      evolution of fruit weight in tomato. Collectively, these findings enhance our
      understanding of GRAS2 functions, in fruit development of tomato, and demonstrate
      a strong association between the GRAS gene family and fruit development.

PMID- 29359474
TI  - Authors' reply re: Peripartum hysterectomy: an economic analysis of direct
      healthcare costs using routinely collected data.

PMID- 29359475
TI  - Incidence of neuromyelitis optica spectrum disorder in the Central Denmark
      Region.
AB  - OBJECTIVES: Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) may be
      misdiagnosed as multiple sclerosis. The aim of this study was to (i) to measure
      AQP4-IgG in patients who fulfilled the clinical and radiological criteria of
      NMOSD in the Central Denmark Region and (ii) to estimate the incidence of NMOSD
      in the region, according to both the 2006 Wingerchuk criteria and the 2015
      International Panel for NMO Diagnosis criteria. MATERIALS AND METHODS: Medical
      records of all patients diagnosed with a demyelinating disorder in the region
      from 1 January 2012 to 31 December 2013 were reviewed. Patients were classified
      as having (i) "NMO" if the 2006 criteria were met, (ii) "NMOSD with AQP4-IgG" or
      (iii) "NMOSD without/unknown AQP-IgG" if the new 2015 NMOSD criteria were met.
      Patients with core symptoms were invited to provide a blood sample for AQP4-IgG
      analysis with an enzyme-linked immunosorbent assay and a cell-based indirect
      immunofluorescence assay. RESULTS: In 191 patients with core symptoms, one met
      the 2015 NMOSD with AQP4-IgG criteria. Two patients met the 2006 NMO and 2015
      NMOSD without/unknown AQP4-IgG criteria. Among 108 patients providing a blood
      sample, all were seronegative. The estimated incidence of NMO (2006 criteria) and
      NMOSD (2015 criteria) was 0.08 and 0.12 per 100 000 person-years, respectively.
      CONCLUSION: NMO/NMOSD is a rare disease in the Central Denmark Region, with a
      considerably lower incidence rate than previously estimated in a neighbouring
      region.

PMID- 29359476
TI  - Spatial cognition and science achievement: The contribution of intrinsic and
      extrinsic spatial skills from 7 to 11 years.
AB  - BACKGROUND: Prior longitudinal and correlational research with adults and
      adolescents indicates that spatial ability is a predictor of science learning and
      achievement. However, there is little research to date with primary-school aged
      children that addresses this relationship. Understanding this association has the
      potential to inform curriculum design and support the development of early
      interventions. AIMS: This study examined the relationship between primary-school
      children's spatial skills and their science achievement. METHOD: Children aged 7
      11 years (N = 123) completed a battery of five spatial tasks, based on a model of
      spatial ability in which skills fall along two dimensions: intrinsic-extrinsic;
      static-dynamic. Participants also completed a curriculum-based science
      assessment. RESULTS: Controlling for verbal ability and age, mental folding
      (intrinsic-dynamic spatial ability), and spatial scaling (extrinsic-static
      spatial ability) each emerged as unique predictors of overall science scores,
      with mental folding a stronger predictor than spatial scaling. These spatial
      skills combined accounted for 8% of the variance in science scores. When
      considered by scientific discipline, mental folding uniquely predicted both
      physics and biology scores, and spatial scaling accounted for additional variance
      in biology and variance in chemistry scores. The children's embedded figures task
      (intrinsic-static spatial ability) only accounted for variance in chemistry
      scores. The patterns of association were consistent across the age range.
      CONCLUSION: Spatial skills, particularly mental folding, spatial scaling, and
      disembedding, are predictive of 7- to 11-year-olds' science achievement. These
      skills make a similar contribution to performance for each age group.

PMID- 29359477
TI  - Understanding the determinants of hemoglobin and iron status: adolescent-adult
      women comparisons in SANHANES-1.
AB  - The study compared hemoglobin (Hb) and serum ferritin levels between adolescent
      and adult women with different body mass indices, dietary intake, and
      sociodemography. A secondary analysis of data for 3177 South African women ?15
      years of age who participated in the SANHANES-1 study was undertaken. Abnormal Hb
      (<=12 g/dL) and serum ferritin (<15 MUg/mL) were based on the World Health
      Organization's criteria for nonpregnant women aged ?15 years. Data were analyzed
      using STATA version 11. Overall, anemia was detected in 740 (23.3%) participants.
      Of the individuals in the subsample (n = 1123, 15-35 years) who had serum
      ferritin measured, 6.0% presented with iron depletion (ID) and 10.8% presented
      with iron-deficiency anemia (IDA). The highest prevalences of anemia, ID, and IDA
      were in 15- to 18-year-olds (11.2%, 8.8%, and 20.2%, respectively). Black young
      adults (19-24 years) were up to 40 times more likely to present with ID compared
      with their non-black counterparts. While overweight adolescents were three times
      more likely to be anemic, overweight and obese young adults, as well as obese
      older adults (25-35 years), were less likely to be anemic compared with normal
      weight women of all age groups. Overconsumption of dietary fat increased ID by up
      to 54- and 11-fold (adolescents and 25- to 35-year-olds, respectively). In South
      Africa, anemia is most prevalent in adolescents and black women. Anemia is also
      an indicator of overconsumption of dietary fat and a marker of socioeconomic
      disadvantage.

PMID- 29359478
TI  - Femoral rotational asymmetry is a common anatomical variant.
AB  - The sulcus line (SL) is a three-dimensional landmark that corrects for individual
      variation in the coronal alignment of the trochlear groove in contrast to the
      traditional Whiteside's line (WL). Femoral rotational asymmetry (FRA) is an
      anatomical variation in which the posterior condyles and trochlear groove are not
      perpendicular to each other. This study aims to measure the SL and assess its
      reliability relative to WL, in addition to measuring and classifying the FRA. A
      retrospective analysis of a series of 191 CT scans of nonarthritic knees was
      performed. Measurements were taken of rotational landmarks in three-dimensional
      reconstructions. The variability and outlier rate of SL was less than WL (P <
      0.05), however, it was also greater than the posterior condylar line (PC) (P <
      0.05). Averaging the PC + 3 degrees  and the SL did not change the rate of
      femoral malrotation relative to the surgical epicondylar axis (SEA) (P > 0.05),
      however it decreased the rate of change of the rotational alignment of the
      trochlear groove between the native knee and the prosthetic knee from 31% to 5%
      (P < 0.05). FRA was classified and was >5 degrees  in 56/191 (29%) of cases. The
      SL technique is more accurate than WL for determining the rotational alignment of
      the trochlear groove. Nonarthritic femora have a high rate of rotational
      asymmetry. Identifying and classifying FRA in individual cases allows the femoral
      component to be inserted in a position which gives the best possible match to
      both the native posterior condyles and trochlear groove. Clin. Anat. 31:551-559,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29359479
TI  - Myhre syndrome: Age-dependent progressive phenotype.

PMID- 29359481
TI  - Letter to 'Knowledge and perceptions of Zika virus among reproductive-aged women
      after public announcement of local mosquito-borne transmission'.

PMID- 29359480
TI  - The effects of fish oil on gene expression in patients with polycystic ovary
      syndrome.
AB  - BACKGROUND: This study was conducted to determine the effects of fish oil
      administration on gene expression related to insulin, lipid and inflammation in
      women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: This
      randomized, double-blind, placebo-controlled trial was conducted among 40
      subjects with PCOS, aged 18-40 years. Subjects were randomly allocated into two
      groups to take either 1000 mg omega-3 fatty acids from fish oil (n = 20) or
      placebo (n = 20) twice a day for 12 weeks. Gene expression related to insulin,
      lipid and inflammation was quantified in peripheral blood mononuclear cells
      (PBMC) of PCOS women with RT-PCR method. RESULTS: Our study demonstrated that
      after the 12-week intervention, compared with the placebo, fish oil
      supplementation upregulated gene expression of peroxisome proliferator-activated
      receptor gamma (PPAR-gamma) (P < .001) in PBMC of subjects with PCOS. In
      addition, compared to the placebo, taking fish oil supplements downregulated gene
      expression of interleukin-1 (IL-1) (P = .02) and interleukin-8 (IL-8) (P = .01)
      in PBMC of subjects with PCOS. We did not observe any significant effect of fish
      oil supplementation on gene expression of lipoprotein(a) [LP(a)], low-density
      lipoprotein receptor (LDLR), glucose transporter 1 (GLUT-1), tumour necrosis
      factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) in PBMC
      of subjects with PCOS. CONCLUSIONS: Overall, fish oil supplementation for 12
      weeks to subjects with PCOS significantly improved gene expression of PPAR-gamma,
      IL-1 and IL-8, but did not influence gene expression of LP(a), LDLR, GLUT-1, TNF
      alpha and TGF-beta.

PMID- 29359482
TI  - Systems thinking and incivility in nursing practice: An integrative review.
AB  - BACKGROUND AND PURPOSE: There is a critical need for nurses and interprofessional
      healthcare providers to implement systems thinking (ST) across international
      borders, addressing incivility and its perilous effects on patient quality and
      safety. An estimated one million patients die in hospitals worldwide due to
      avoidable patient-related errors. Establishing safe and civil workplaces using ST
      is paramount to promoting clear, level-headed thinking from which patient
      centered nursing actions can impact health systems. The purpose of the paper is
      to answer the research question, What ST evidence fosters the effect of workplace
      civility in practice settings? METHODS: Whittemore and Knafl's integrative review
      method guided this study. The quality of articles was determined using Chu et
      al.'s Mixed Methods Assessment Tool. RESULTS: Thirty-eight studies were reviewed.
      Themes emerged describing antecedents and consequences of incivility as embedded
      within complex systems, suggesting improvements for civility and systems/ST in
      nursing practice. IMPLICATIONS FOR PRACTICE: This integrative review provides
      information about worldwide incivility in nursing practice from a systems
      perspective. Several models are offered as a means of promoting civility in
      nursing practice to improve patient quality and safety. Further study is needed
      regarding incivility and resultant effects on patient quality and safety.

PMID- 29359483
TI  - Highly Sensitive Bioluminescent Probe for Thiol Detection in Living Cells.
AB  - The sensitive detection of thiols including glutathione and cysteine is desirable
      owing to their roles as indispensable biomolecules in maintaining intracellular
      biological redox homeostasis. Herein, we report the design and synthesis of SEluc
      1 (sulfinate ester luciferin), a chemoselective probe exhibiting a ratiometric
      and turn-on response towards thiols selectively in fluorescence and
      bioluminescence, respectively. The probe, which was designed based on the "caged"
      luciferin strategy, displays excellent selectivity, high signal/noise ratio (>240
      in the case of bioluminescence), and a biologically relevant limit of detection
      (LOD, 80 nm for cysteine), which are all desirable traits for a sensitive
      bioluminescent sensor. SEluc-1 was further applied to fluorescence imaging of
      thiol activity in living human cervical cancer HeLa cell cultures, and was
      successfully able to detect fluctuations in thiol concentrations induced by
      oxidative stress in a bioluminescent assay utilizing African green monkey
      fibroblast COS-7 cells and human breast adenocarcinoma MCF-7 cells.

PMID- 29359485
TI  - Australian family carer responses when a loved one receives a diagnosis of Motor
      Neurone Disease-"Our life has changed forever".
AB  - While the experiences of family members supporting a person with a terminal
      illness are well documented, less is known about the needs of carers of people
      with neurological diseases, in particular, Motor Neurone Disease (MND). This
      paper describes the qualitative data from a large Australian survey of family
      carers of people with MND, to ascertain their experiences of receiving the
      diagnosis. The aim of the study was to describe the experiences of family carers
      of people with MND in receiving the diagnosis in order to inform and improve ways
      in which the diagnosis is communicated. Anonymous postal surveys were sent to
      people with MND in Australia and their family carers respectively. The perceived
      ability/skills of neurologists was assessed using a five-point scale from
      excellent to poor. Attributes of communication of bad news was measured by the
      SPIKES protocol. Each survey question invited further written responses. Eight
      hundred and sixty-four questionnaires were posted to people with MND and their
      family carers, with assistance from MND associations. One hundred and ninety-six
      family carers submitted responses, of which 171 (88%) were patient-carer dyads.
      Analyses were conducted on 190 family carers. Five themes emerged from reading
      and re-reading written responses: frustrations with the diagnosis; giving
      information; family carer observations of the neurologist; the setting; and what
      would have made the diagnosis easier? The delivery of the diagnosis is a pivotal
      event in the MND trajectory. Satisfaction for patients and their family carers is
      related to the neurologists showing empathy and responding appropriately to their
      emotions, exhibiting knowledge and providing longer consultations. Neurologists
      may benefit from education and training in communication skills to adequately
      respond to patients' and families' emotions and development of best practice
      protocols.

PMID- 29359484
TI  - Utility of Pathology Imagebase for standardisation of prostate cancer grading.
AB  - AIMS: Despite efforts to standardise grading of prostate cancer, even among
      experts there is still a considerable variation in grading practices. In this
      study we describe the use of Pathology Imagebase, a novel reference image
      library, for setting an international standard in prostate cancer grading.
      METHODS AND RESULTS: The International Society of Urological Pathology (ISUP)
      recently launched a reference image database supervised by experts. A panel of 24
      international experts in prostate pathology reviewed independently
      microphotographs of 90 cases of prostate needle biopsies with cancer. A linear
      weighted kappa of 0.67 (95% confidence interval = 0.62-0.72) and consensus was
      reached in 50 cases. The interobserver weighted kappa varied from 0.48 to 0.89.
      The highest level of agreement was seen for Gleason score (GS) 3 + 3 = 6 (ISUP
      grade 1), while higher grades and particularly GS 4 + 3 = 7 (ISUP grade 3) showed
      considerable disagreement. Once a two-thirds majority was reached, images were
      moved automatically into a public database available for all ISUP members at
      www.isupweb.org. Non-members are able to access a limited number of cases.
      CONCLUSIONS: It is anticipated that the database will assist pathologists to
      calibrate their grading and, hence, decrease interobserver variability. It will
      also help to identify instances where definitions of grades need to be clarified.

PMID- 29359486
TI  - Four-fold Channel-Nicked Human Ferritin Nanocages for Active Drug Loading and pH
      Responsive Drug Release.
AB  - Human ferritins are emerging platforms for non-toxic protein-based drug delivery,
      owing to their intrinsic or acquirable targeting abilities to cancer cells and
      hollow cage structures for drug loading. However, reliable strategies for high
      level drug encapsulation within ferritin cavities and prompt cellular drug
      release are still lacking. Ferritin nanocages were developed with partially
      opened hydrophobic channels, which provide stable routes for spontaneous and
      highly accumulated loading of FeII -conjugated drugs as well as pH-responsive
      rapid drug release at endoplasmic pH. Multiple cancer-related compounds, such as
      doxorubicin, curcumin, and quercetin, were actively and heavily loaded onto the
      prepared nicked ferritin. Drugs on these minimally modified ferritins were
      effectively delivered inside cancer cells with high toxicity.

PMID- 29359487
TI  - Review article: long-term safety of oral anti-viral treatment for chronic
      hepatitis B.
AB  - BACKGROUND: Safety profile of nucleos(t)ide analogues is an important issue in
      view of its widespread use for decades in patients with chronic hepatitis B
      (CHB). AIM: To review and evaluate the latest evidence on the safety profiles of
      the six approved nucleoside analogues. METHODS: Relevant articles related to
      nucleoside analogue safety were selected for review following extensive language-
      and date-unrestricted, electronic searches of the literature. RESULTS:
      Nephrotoxicity has been well reported in patients receiving older generations of
      nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate
      (TDF). Yet risks of renal failure and renal replacement therapy were similar in
      patients treated with nucleoside analogues versus nucleotide analogues in real
      life setting. Bone toxicity is closely related to nucleoside analogue effect on
      renal proximal tubular and phosphaturia. Real-life data demonstrated increased
      risk of hip fracture in patients receiving adefovir but not TDF. The newly
      approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles
      compared to TDF. Long-term use of nucleoside analogues eg entecavir does not
      increase the risk of other cancers. Muscular toxicity may be seen in telbivudine
      treated patients so regular monitoring is advised. Peripheral neuropathy and
      lactic acidosis are rare adverse events. Latest international guidelines support
      the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not
      contraindicated during TDF therapy. CONCLUSIONS: Long-term safety profile of
      nucleoside analogues is now better defined with more data from large real-life
      cohorts and clinical trials with long-term follow-up. The new nucleotide
      analogue, TAF is now available with favourable renal and bone safety profiles.

PMID- 29359488
TI  - Mechanoelectrical transduction in chondrocytes.
AB  - Cartilage tissue lines the joints of mammals, helping to lubricate joint movement
      and distribute mechanical loads. This tissue is comprised of isolated cells known
      as chondrocytes which are embedded in an extracellular matrix. Chondrocytes
      produce and maintain the cartilage by sensing and responding to changing
      mechanical loads. Mechanosensitive ion channels have been implicated in
      chondrocyte mechanotransduction and recent studies have shown that both PIEZO1
      and TRPV4 can be activated by mechanical stimuli in these cells. The 2 channels
      mediate separate but overlapping mechanoelectrical transduction pathways, PIEZO1
      in response to stretch and substrate deflections and TRPV4 in response to
      substrate deflections alone. These distinct pathways of mechanoelectrical
      transduction suggest a mechanism by which chondrocytes can distinguish between
      different stimuli that arise in their complex mechanical environment.

PMID- 29359490
TI  - Taking Lillian at her word.

PMID- 29359489
TI  - Knowledge, attitude and practice among Health Visitors in the United Kingdom
      toward children's oral health.
AB  - OBJECTIVES: The purpose of this study was to determine knowledge, attitude, and
      practical behavior of health visitors regarding children's oral health in the
      United Kingdom (UK). METHODS: A web-based self-administered survey with 18 closed
      and 2 open ended questions was distributed to a convenience sample of
      approximately 9,000 health visitors who were currently employed in the United
      Kingdom and a member of the Institute of Health Visiting. RESULTS: A total of
      1,088 health visitors completed the survey, resulting in a response rate of 12%.
      One-third of the health visitors reported that they had not received oral health
      training previously. Almost all agreed that oral health advice/promotion should
      be included in their routine health visiting contacts. Previous oral health
      training/education was associated with an increase in oral health knowledge;
      confidence in entering a discussion with parents/caregivers and willingness to be
      involved in dental referral process. CONCLUSIONS: The results of our study
      support the need for health visitors to receive oral health training in oral
      health promotion including oral health risk assessment, guidance on evidence
      based up-to-date prevention measures, increasing the dental attendance prevalence
      at early stages and awareness of including specific oral health guidelines/fact
      sheets into their regular practice.

PMID- 29359491
TI  - Does spotty calcification attenuate the response of nonculprit plaque to statin
      therapy?: A serial optical coherence tomography study.
AB  - OBJECTIVES: The aim of this study was to determine if spotty calcification
      decreases the response of plaque progression to statin therapy. BACKGROUND:
      Previous studies showed that the presence of spotty calcification is a marker of
      vulnerable plaque. However, the relationship between spotty calcification and
      plaque progression is not clear. METHODS: Ninety-six nonculprit lipid-rich
      plaques in 69 patients who received serial optical coherence tomography (OCT)
      imaging were included. Plaques were divided into three groups: spotty
      calcification (n = 38), calcified (n = 12) and noncalcified (n = 46) plaques.
      Spotty calcification was identified by the presence of a lesion <4 mm in length
      with an arc of calcification <90 degrees . Changes in plaque characteristics and
      fibrous cap thickness (FCT) at 6 and 12 months under statin therapy were analyzed
      by OCT. RESULTS: The increase of FCT was sustained from baseline to 6 and 12
      months in three groups: spotty calcification (62.8 +/- 20.9, 126.4 +/- 84.9, and
      169.2 +/- 81.6 MUm, respectively; P < .001), calcified (59.8 +/- 17.0, 93.4 +/-
      51.4, and 155.2 +/- 61.7 MUm, respectively; P < .001) and noncalcified (60.0 +/-
      17.2, 125.5 +/- 62.1, and 161.0 +/- 80.5 MUm, respectively; P < .001). Intensive
      statin induced a greater change in FCT at 12 months than moderate statin in the
      spotty calcification group (P = 0.034). The mean lipid arc decreased
      significantly at 12 months from baseline in the three groups (P = 0.004, P =
      0.023, and P < .001, respectively). CONCLUSIONS: Statin therapy was effective for
      plaque stabilization in plaques with and without spotty calcification. Patients
      with spotty calcification benefitted more from intensive statin than from
      moderate statin therapy.

PMID- 29359492
TI  - Cost-effectiveness of universal and targeted newborn screening for congenital
      cytomegalovirus infection.

PMID- 29359493
TI  - Axially chiral Ni(II) complexes of alpha-amino acids: Separation of enantiomers
      and kinetics of racemization.
AB  - Herein we present design, synthesis, chiral HPLC resolution, and kinetics of
      racemization of axially chiral Ni(II) complexes of glycine and di-(benzyl)glycine
      Schiff bases. We found that while the ortho-fluoro derivatives are
      configurationally unstable, the pure enantiomers of corresponding axially chiral
      ortho-chloro-containing complexes can be isolated by preparative HPLC and show
      exceptional configurational stability (t1/2 from 4 to 216 centuries) at ambient
      conditions. Synthetic implications of this discovery for the development of new
      generation of axially chiral auxiliaries, useful for general asymmetric synthesis
      of alpha-amino acids, are discussed.

PMID- 29359494
TI  - The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular
      "Inside-Out" Approach.
AB  - Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7
      diazabicyclo[3.3.1]nonane) to which combinations of an alpha,N-fused 2-pyridone,
      an endo- or exo-alpha,N-annulated piperidin(on)e, and an exo-allyl substituent
      are attached. We developed a modular "inside-out" approach that permits access to
      most members of this class. Its applicability was proven in the asymmetric
      synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten
      first enantioselective total syntheses. Key steps are the first successful
      preparation of both enantiomers of C2 -symmetric 2,6-dioxobispidine by
      desymmetrization of a 2,4,6,8-tetraoxo precursor, the construction of the alpha,N
      fused 2-pyridone by using an enamine-bromoacrylic acid strategy, and the
      installation of endo- or, optionally, exo-annulated piperidin(on)es.

PMID- 29359495
TI  - Screening of a Drug Library Identifies Inhibitors of Cell Intoxication by CNF1.
AB  - Cytotoxic necrotizing factor 1 (CNF1) is a toxin produced by pathogenic strains
      of Escherichia coli responsible for extra-intestinal infections. CNF1 deamidates
      Rac1, thereby triggering its permanent activation and worsening inflammatory
      reactions. Activated Rac1 is prone to proteasomal degradation. There is no
      targeted therapy against CNF1, despite its clinical relevance. In this work we
      developed a fluorescent cell-based immunoassay to screen for inhibitors of CNF1
      induced Rac1 degradation among 1120 mostly approved drugs. Eleven compounds were
      found to prevent CNF1-induced Rac1 degradation, and five also showed a protective
      effect against CNF1-induced multinucleation. Finally, lasalocid, monensin,
      bepridil, and amodiaquine protected cells from both diphtheria toxin and CNF1
      challenges. These data highlight the potential for drug repurposing to fight
      several bacterial infections and Rac1-based diseases.

PMID- 29359496
TI  - The transient receptor potential vanilloid-3 regulates hypoxia-mediated pulmonary
      artery smooth muscle cells proliferation via PI3K/AKT signaling pathway.
AB  - OBJECTVES: Transient receptor potential vanilloid 3 (TRPV3) is a member of the
      TRP channels family of Ca2+ -permeant cation channels. In this study, we aim to
      investigate the role of TRPV3 in pulmonary vascular remodeling and PASMCs
      proliferation under hypoxia. MATERIALS AND METHODS: The expression of TRPV3 was
      evaluated in patients with pulmonary arterial hypertension (PAH) and hypoxic
      rats, using hematoxylin and eosin (H&E) and immunohistochemistry. In vitro, MTT
      assay, flow cytometry, Western blotting and immunofluorescence were performed to
      investigate the effects of TRPV3 on proliferation of PASMCs. RESULTS: We found
      that, in vivo, the expression of TRPV3 was increased in patients with PAH and
      hypoxic rats. Right ventricular hypertrophy measurements and pulmonary
      pathomorphology data show that the ratio of the heart weight/tibia length
      (HW/TL), the right ventricle/left ventricle plus septum (RV/LV+S) and the medial
      width of the pulmonary artery were increased in chronic hypoxic rats. Moreover,
      the expression of proliferating cell nuclear antigen (PCNA), Cyclin D, Cyclin E
      and Cyclin A, phospho-CaMKII (p-CaMKII) were induced by hypoxia. In vitro, we
      revealed that hypoxia promoted PASMCs viability, increased the expression of
      PCNA, Cyclin D, Cyclin E, Cyclin A p-CaMKII, made more cells from G0 /G1 phase to
      G2 /M + S phase, enhanced the microtubule formation, and increased [Ca2+ ]i ,
      which could be suppressed by Ruthenium Red, an inhibitor of TRPV3, and TRPV3
      silencing has similar effects. Furthermore, the up-regulated expression of PCNA,
      Cyclin D, Cyclin E and Cyclin A, the increased number of cells in G2 /M and S
      phase, and the enhanced activation and expression of PI3K and AKT proteins
      induced by hypoxia and in presence of carvacrol (an agonist of TRPV3), was
      significantly attenuated by incubation of LY 294002, a specific inhibitor for
      PI3K/AKT. CONCLUSIONS: These findings suggest that TRPV3 is involved in hypoxia
      induced pulmonary vascular remodeling and promotes proliferation of PASMCs and
      the effect is, at least in part, mediated via the PI3K/AKT pathway.

PMID- 29359497
TI  - Adoption of the transradial approach for percutaneous coronary intervention and
      rates of vascular complications following transfemoral procedures: Insights from
      NCDR.
AB  - OBJECTIVES: This study was designed to examine the association between adopting
      the transradial approach for percutaneous coronary intervention (PCI) and rates
      of vascular complications following transfemoral PCI. BACKGROUND: Recent studies
      raised concerns that operators adopting the transradial approach may lose their
      transfemoral access skills and experience increased rates of vascular
      complications. METHODS: Retrospective analysis of data from the NCDR CathPCI
      Registry to examine the rates of vascular complications among physicians who were
      femoral operators (>90% of cases) in 2010-2011 and later adopted the transradial
      approach to PCI among low-, intermediate-, or high-level adopters (<=33%, 34-66%,
      and >66%, respectively) in 2014-2015. Propensity score matching was used to
      control for confounding factors. RESULTS: A total of 1,704,708 procedures
      performed by 4,697 operators were included. Most operators were low-level
      adopters (80.7%), followed by intermediate (15.7) and high-level adopters (3.6%).
      Compared to the preadoption period, vascular complications of transfemoral PCIs
      following transradial adoption increased among low-level adopters (1.29%-1.59%,
      adjusted OR [95% CI]: 1.24[1.20-1.28], P < 0.001), intermediate-level adopters
      (1.37%-1.92%, adjusted OR 1.40[1.29-1.53], P < 0.001), and high-level adopters
      (1.54%-1.93%, adjusted OR 1.26[1.00-1.58], P = 0.053).In the post-adoption
      period, there was increase in access site bleeding that is likely due to change
      in registry definition. There was no increase in hematomas, retroperitoneal
      bleeding or other vascular complications. CONCLUSIONS: Adoption of the
      transradial approach for PCI is not associated with clinically meaningful
      increase in rates of vascular complications of transfemoral PCIs.

PMID- 29359498
TI  - Time-dependent differences in cortical measures and their associations with
      behavioral measures following mild traumatic brain injury.
AB  - There is currently a critical need to establish an improved understanding of time
      dependent differences in brain structure following mild traumatic brain injury
      (mTBI). We compared differences in brain structure, specifically cortical
      thickness (CT), cortical volume (CV), and cortical surface area (CSA) in 54
      individuals who sustained a recent mTBI and 33 healthy controls (HCs).
      Individuals with mTBI were split into three groups, depending on their time since
      injury. By comparing structural measures between mTBI and HC groups, differences
      in CT reflected cortical thickening within several areas following 0-3 (time
      point, TP1) and 3-6 months (TP2) post-mTBI. Compared with the HC group, the mTBI
      group at TP2 showed lower CSA within several areas. Compared with the mTBI group
      at TP2, the mTBI group during the most chronic stage (TP3: 6-18 months post-mTBI)
      showed significantly higher CSA in several areas. All the above reported
      differences in CT and CSA were significant at a cluster-forming p < .01
      (corrected for multiple comparisons). We also found that in the mTBI group at
      TP2, CT within two clusters (i.e., the left rostral middle frontal gyrus (L.
      RMFG) and the right postcentral gyrus (R. PostCG)) was negatively correlated with
      basic attention abilities (L. RMFG: r = -.41, p = .05 and R. PostCG: r = -.44, p
      = .03). Our findings suggest that alterations in CT and associated
      neuropsychological assessments may be more prominent during the early stages of
      mTBI. However, alterations in CSA may reflect compensatory structural recovery
      during the chronic stages of mTBI.

PMID- 29359499
TI  - Laparoscopic transabdominal cerclage: Outcomes of 121 pregnancies.
AB  - BACKGROUND: Cervical insufficiency is a significant cause of morbidity and
      mortality. Cervical cerclage is one option in the management of cervical
      insufficiency. AIM: To evaluate obstetric outcomes following insertion of a pre
      pregnancy laparoscopic transabdominal cerclage in women at high risk for pre-term
      labour and/or mid-trimester pregnancy loss. METHODS: A prospective observational
      study of consecutive women who underwent laparoscopic transabdominal cerclage
      from 2007 to 2017. Eligible women had a diagnosis of cervical insufficiency based
      on previous obstetric history and/or a short or absent cervix and were considered
      not suitable for a transvaginal cerclage. The primary outcome was neonatal
      survival and the secondary outcome was delivery of an infant at >=34 weeks
      gestation. Surgical morbidity and complications were also evaluated. RESULTS:
      During the study period, 225 women underwent laparoscopic transabdominal
      cerclage. We present the outcomes of 121 pregnancies resulting in 125 babies. The
      perinatal survival rate of viable pregnancies was 98.5% with a mean gestational
      age at delivery of 35.2 weeks; 79.7% of babies were delivered at >=34.0 weeks
      gestation. CONCLUSION: Laparoscopic transabdominal cerclage is a safe and
      effective procedure resulting in favourable obstetric outcomes in women with a
      poor obstetric history. For optimal success the procedure requires the correct
      surgical expertise, equipment and appropriate patient selection.

PMID- 29359500
TI  - Simultaneous analysis of tropane alkaloids in teas and herbal teas by liquid
      chromatography coupled to high-resolution mass spectrometry (Orbitrap).
AB  - A new method has been developed for the simultaneous determination of 13 tropane
      alkaloids in tea and herbal teas using high-performance liquid chromatography
      coupled to an Exactive-Orbitrap analyzer. A mixture of methanol, water, and
      formic acid was used for the extraction of the target compounds followed by a
      solid-phase extraction step. The validated method provided recoveries from 75 to
      128% with intra- and interday precision lower than or equal to 24% (except for
      apoatropine). Limits of quantification ranged from 5 to 20 MUg/kg. Eleven tea and
      herbal tea samples and two contaminated samples with Datura stramonium seeds were
      analyzed. Tropane alkaloids were detected in six samples with concentrations from
      5 (apoatropine) to 4340 MUg/kg (sum of physoperuvine, pseudotropine, and
      tropine), whereas concentrations from 5 (apoatropine) to 1725 MUg/kg (sum of
      physoperuvine, pseudotropine, and tropine) were found in the contaminated
      samples.

PMID- 29359501
TI  - Rhodium(I)-Catalyzed Cycloisomerization of Homopropargylallene-Alkynes through
      C(sp3 )-C(sp) Bond Activation.
AB  - Upon exposure to a catalytic amount of [RhCl(CO)2 ]2 in 1,4-dioxane,
      homopropargylallene-alkynes underwent a novel cycloisomerization accompanied by
      the migration of the alkyne moiety of the homopropargyl functional group to
      produce six/five/five tricyclic compounds in good yields. A plausible mechanism
      was proposed on the basis of an experiment with 13 C-labeled substrate. The
      resulting tricyclic derivatives were further converted into the corresponding
      bicyclo[3.3.0] skeletons with vicinal cis dihydroxy groups.

PMID- 29359502
TI  - Survival rates indicate that correlations between community-weighted mean traits
      and environments can be unreliable estimates of the adaptive value of traits.
AB  - Correlations between community-weighted mean (CWM) traits and environmental
      gradients are often assumed to quantify the adaptive value of traits. We tested
      this assumption by comparing these correlations with models of survival
      probability using 46 perennial species from long-term permanent plots in pine
      forests of Arizona. Survival was modelled as a function of trait * environment
      interactions, plant size, climatic variation and neighbourhood competition. The
      effect of traits on survival depended on the environmental conditions, but the
      two statistical approaches were inconsistent. For example, CWM-specific leaf area
      (SLA) and soil fertility were uncorrelated. However, survival was highest for
      species with low SLA in infertile soil, a result which agreed with expectations
      derived from the physiological trade-off underpinning leaf economic theory. CWM
      trait-environment relationships were unreliable estimates of how traits affected
      survival, and should only be used in predictive models when there is empirical
      support for an evolutionary trade-off that affects vital rates.

PMID- 29359503
TI  - A General Strategy to Access Structural Information at Atomic Resolution in
      Polyglutamine Homorepeats.
AB  - Homorepeat (HR) proteins are involved in key biological processes and multiple
      pathologies, however their high-resolution characterization has been impaired due
      to their homotypic nature. To overcome this problem, we have developed a strategy
      to isotopically label individual glutamines within HRs by combining nonsense
      suppression and cell-free expression. Our method has enabled the NMR
      investigation of huntingtin exon1 with a 16-residue polyglutamine (poly-Q) tract,
      and the results indicate the presence of an N-terminal alpha-helix at near
      neutral pH that vanishes towards the end of the HR. The generality of the
      strategy was demonstrated by introducing a labeled glutamine into a pathological
      version of huntingtin with 46 glutamines. This methodology paves the way to
      decipher the structural and dynamic perturbations induced by HR extensions in
      poly-Q-related diseases. Our approach can be extended to other amino acids to
      investigate biological processes involving proteins containing low-complexity
      regions (LCRs).

PMID- 29359504
TI  - Stenting for middle aortic syndrome caused by Takayasu arteritis-immediate and
      long-term outcomes.
AB  - OBJECTIVE: To evaluate immediate and long-term clinical outcomes of stenting for
      middle aortic syndrome (MAS) caused by Takayasu arteritis (TA). BACKGROUND:
      Studies of endovascular stenting for the treatment of MAS caused by TA are scare.
      METHODS: Data from 48 consecutive TA patients (mean 33.3 +/- 12.6 years) with MAS
      treated by stenting in our institution between January 2010 and July 2016 were
      collected and retrospectively analyzed. Thirty-day and long-term follow-up
      clinical outcomes after aorta stenting were assessed. RESULTS: Stenting was
      successful in all patients. The mean stenosis and peak systolic pressure gradient
      of aorta lesions were reduced from 81.3 +/- 8.0% and 70.7 +/- 18.4 mm Hg to 14.7
      +/- 8.3% and 14.0 +/- 5.8 mm Hg immediately after the 54 stents were implanted.
      One patient developed retroperitoneal hemorrhage and one developed flow-limiting
      dissection that involved bilateral renal arteries perioperatively. Both patients
      recovered without sequela. Compared with baseline, the ankle brachial index (0.92
      +/- 0.19 vs. 0.75 +/- 0.22), mean systolic blood pressure (149.5 +/- 19.1 vs.
      179.0 +/- 28.4 mm Hg) and antihypertensive drugs (1.1 +/- 0.7 vs. 3.1 +/- 0.9)
      significantly improved after an average follow-up of 3.1 years (all P < .001). A
      total of 5 (10.9%) patients developed in-stent restenosis, which were resolved by
      reintervention (restenting in 3 patients and re-angioplasty alone in 2 patients).
      No major adverse events occurred during follow up. CONCLUSIONS: Percutaneous
      aortic stenting is highly efficacious and safe in treating patients with MAS
      caused by TA with good immediate and long-term clinical outcomes.

PMID- 29359505
TI  - Maternal-choice caesarean section versus planned vaginal birth in low-risk
      primigravid women.
AB  - Rising rates of caesarean section (CS) have been attributed, in part, to maternal
      choice CS (MCCS). There are few published data regarding maternal and perinatal
      risks comparing MCCS with planned vaginal birth (VB) in uncomplicated first
      pregnancies to inform choice. We report the results of a pragmatic patient
      preference cohort study of private patients in Australia: 64 women planning MCCS
      and 113 women planning VB. There were few differences in outcome between the two
      groups. The study highlighted the well-recognised difficulties in undertaking
      prospective research into MCCS.

PMID- 29359506
TI  - First-in-human implantation of a novel self-expanding supra-annular transcatheter
      heart valve for transcatheter aortic valve implantation inside a small
      degenerated aortic surgical bioprosthesis.
AB  - With next-generation valves such as the ALLEGRA valve from NewValve Technologies
      (NVT), Hechingen Germany, there is a very likely treatment expansion for patients
      with aortic valve disease. Besides treatment of native valvular aortic stenosis
      with the ALLEGRA valve, the special implant mechanism seems to be an appealing
      concept for patients with degenerated surgical bioprostheses. We report the first
      case of a transfemoral implantation in small degenerated surgical bioprosthesis
      of a 76-year-old woman.

PMID- 29359507
TI  - Immune checkpoint inhibitors in cancer therapy: a focus on T-regulatory cells.
AB  - Regulatory T cells (Tregs) play essential roles in immune homeostasis; however,
      their role in tumor microenvironment (TME) is not completely evident. Several
      studies reported that infiltration of Tregs into various tumor tissues promotes
      tumor progression by limiting antitumor immunity and supporting tumor immune
      evasion. Furthermore, in TME, Tregs include heterogeneous subsets of cells
      expressing different immunosuppressive molecules favoring tumor progression. For
      an effective cancer therapy, it is critical to understand the Treg heterogeneity
      and biology in the TME. Recent studies have shown that immune checkpoint
      molecules promote cancer progression through various antitumor inhibitory
      mechanisms. Recent advances in cancer immunotherapy have shown the promising
      potentials of immune checkpoint inhibitors (ICIs) in inducing antitumor immune
      responses and clinical benefits in patients with cancer at late stages. Most
      studies revealed the effect of ICIs on T effector cells, and little is known
      about their effect on Tregs. In this review, we highlight the effects of the
      ICIs, including anti-CTLA-4, anti-PD-1/PD-L1, anti-LAG-3, anti-TIM-3, and anti
      TIGIT, on tumor-infiltrating and peripheral Tregs to elicit effector T-cell
      functions against tumors. Additionally, we discuss how ICIs may target Tregs for
      cancer immunotherapy.

PMID- 29359508
TI  - Chromosomal deletions mediated by CRISPR/Cas9 in Helicoverpa armigera.
AB  - Helicoverpa armigera, cotton bollworm, is one of the most disastrous pests
      worldwide, threatening various food and economic crops. Functional genomic tools
      may provide efficient approaches for its management. The clustered regularly
      interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)
      system, dependent on a single guide RNA (sgRNA), has been used to induce indels
      for targeted mutagenesis in cotton bollworm. However, genomic deletions may be
      more desirable to disrupt the function of noncoding genes or regulatory
      sequences. By injecting two sgRNAs with Cas9 protein targeting different exons,
      we obtained predictable genomic deletions of several hundred bases. We achieved
      this type of modification with different combinations of sgRNA pairs, including
      HaCad and HaABCC2. Our finding indicated that CRISPR/Cas9 can be used as an
      efficient tool to engineer genomes with chromosomal deletion in H. armigera.

PMID- 29359509
TI  - Survivin is a negative prognostic factor in malignant pleural effusion.
AB  - BACKGROUND: Survivin is a well-known member of the inhibitor of apoptosis family,
      and has been related to increased tumour aggressivity, both in tissue and in
      pleural fluid. OBJECTIVES: In patients with malignant pleural effusion, we sought
      to investigate the changes in pleural fluid survivin concentrations induced by
      talc instillation into the pleural space. Those changes were also examined in
      relation to pleurodesis outcome and patient survival. METHODS: We investigated 84
      patients with malignant pleural effusion who underwent talc pleurodesis. Of them,
      32 had breast cancer, 25 lung cancer and 27 had mesothelioma. Serial samples of
      pleural fluid were obtained before thoracoscopy (baseline) and 24 hours
      thereafter. RESULTS: Survivin levels were successfully quantified in all pleural
      fluid samples, and they were significantly higher in samples obtained after
      thoracoscopic talc poudrage compared with baseline (P < .001). Patients with
      higher pleural fluid survivin levels at baseline had a significantly poorer
      pleurodesis outcome (P = .004). A 30 pg/mL cut-off for baseline survivin in
      pleural fluid predicted failure of pleurodesis with a 54% sensitivity and 79%
      specificity (P = .009). Moreover, median postpleurodesis survival of patients
      with baseline survivin levels >=30 pg/mL was 4 months (range: 0.1-38), compared
      with 13 months (range: 0.1-259) in patients below that cut-off (P < .001).
      CONCLUSION: Elevated pleural fluid survivin concentrations are useful to predict
      failure of pleurodesis and are associated with shorter survival in patients with
      malignant pleural effusion.

PMID- 29359510
TI  - Impact of column and stationary phase properties on the productivity in chiral
      preparative LC.
AB  - By generating 1500 random chiral separation systems, assuming two-site Langmuir
      interactions, we investigated numerically how the maximal productivity (PR,max )
      was affected by changes in stationary phase adsorption properties. The relative
      change in PR,max , when one adsorption property changed 10%, was determined for
      each system and for each studied parameter the corresponding productivity change
      distribution of the systems was analyzed. We could conclude that there is no
      reason to have columns with more than 500 theoretical plates and larger
      selectivity than 3. More specifically, we found that changes in selectivity have
      a major impact on PR,max if it is below ~2 and, interestingly, increasing
      selectivity when it is above ~3 decreases PR,max . Increase in relative
      saturation capacity will have a major impact on PR,max if it is below ~40%, but
      only modest above this percent. Increasing total monolayer saturation capacity,
      or decreasing the first eluting enantiomer's retention factor, will have a modest
      effect on PR,max and increased efficiency will have almost no effect at all on
      PR,max unless it is below ~500 theoretical plates. Finally, we showed that chiral
      columns with superior analytic performance might have inferior preparative
      performance, or vice versa. It is, therefore, not possible to assess columns
      based on their analytical performance alone.

PMID- 29359511
TI  - Residence rule flexibility and descent groups dynamics shape uniparental genetic
      diversities in South East Asia.
AB  - OBJECTIVES: Social organization plays a major role in shaping human population
      genetic diversity. In particular, matrilocal populations tend to exhibit less
      mitochondrial diversity than patrilocal populations, and the other way around for
      Y chromosome diversity. However, several studies have not replicated such
      findings. The objective of this study is to understand the reasons for such
      inconsistencies and further evaluate the influence of social organization on
      genetic diversity. MATERIALS AND METHODS: We explored uniparental diversity
      patterns using mitochondrial HV1 sequences and 17 Y-linked short tandem repeats
      (STRs) in 12 populations (n = 619) from mainland South-East Asia exhibiting a
      wide range of social organizations, along with quantitative ethno-demographic
      information sampled at the individual level. RESULTS: MtDNA diversity was lower
      in matrilocal than in multilocal and patrilocal populations while Y chromosome
      diversity was similar among these social organizations. The reasons for such
      asymmetry at the genetic level were understood by quantifying sex-specific
      migration rates from our ethno-demographic data: while female migration rates
      varied between social organizations, male migration rates did not. This
      unexpected lack of difference in male migrations resulted from a higher
      flexibility in residence rule in patrilocal than in matrilocal populations. In
      addition, our data suggested an impact of clan fission process on uniparental
      genetic patterns. CONCLUSIONS: The observed lack of signature of patrilocality on
      Y chromosome patterns might be attributed to the higher residence flexibility in
      the studied patrilocal populations, thus providing a potential explanation for
      the apparent discrepancies between social and genetic structures. Altogether,
      this study highlights the need to quantify the actual residence and descent
      patterns to fit social to genetic structures.

PMID- 29359512
TI  - Ex vivo allotransplantation engineering: Delivery of mesenchymal stem cells
      prolongs rejection-free allograft survival.
AB  - Current pharmacologic regimens in transplantation prevent allograft rejection
      through systemic recipient immunosuppression but are associated with severe
      morbidity and mortality. The ultimate goal of transplantation is the prevention
      of allograft rejection while maintaining recipient immunocompetence. We
      hypothesized that allografts could be engineered ex vivo (after allotransplant
      procurement but before transplantation) by using mesenchymal stem cell-based
      therapy to generate localized immunomodulation without affecting systemic
      recipient immunocompetence. To this end, we evaluated the therapeutic efficacy of
      bone marrow-derived mesenchymal stem cells in vitro and activated them toward an
      immunomodulatory fate by priming in inflammatory or hypoxic microenvironments.
      Using an established rat hindlimb model for allotransplantation, we were able to
      significantly prolong rejection-free allograft survival with a single
      perioperative ex vivo infusion of bone marrow-derived mesenchymal stem cells
      through the allograft vasculature, in the absence of long-term pharmacologic
      immunosuppression. Critically, transplanted rats rejected a second, nonengineered
      skin graft from the same donor species to the contralateral limb at a later date,
      demonstrating that recipient systemic immunocompetence remained intact. This
      study represents a novel approach in transplant immunology and highlights the
      significant therapeutic opportunity of the ex vivo period in transplant
      engineering.

PMID- 29359513
TI  - Vascular characteristics in young women-Effect of extensive endurance training or
      a sedentary lifestyle.
AB  - AIM: To explore whether high-level endurance training in early age has an
      influence on the arterial wall properties in young women. METHODS: Forty-seven
      athletes (ATH) and 52 controls (CTR), all 17-25 years of age, were further
      divided into runners (RUN), whole-body endurance athletes (WBA), sedentary
      controls (SC) and normally active controls (AC). Two-dimensional ultrasound
      scanning of the carotid arteries was conducted to determine local common carotid
      artery (CCA) geometry and wall distensibility. Pulse waves were recorded with a
      tonometer to determine regional pulse wave velocity (PWV) and pulse pressure
      waveform. RESULTS: Carotid-radial PWV was lower in WBA than in RUN (P < .05),
      indicating higher arterial distensibility along the arm. Mean arterial pressure
      was lower in ATH than in CTR and in RUN than in WBA (P < .05). Synthesized aortic
      augmentation index (AI@75) was lower among ATH than among CTR (-12.8 +/- 1.6 vs 
      2.6 +/- 1.2%, P < .001) and in WBA than in RUN (-16.4 +/- 2.5 vs -10.7 +/- 2.0%,
      P < .05), suggesting a diminished return of reflection waves to the aorta during
      systole. Carotid-femoral PWV and intima-media thickness (IMT), lumen diameter and
      radial distensibility of the CCA were similar in ATH and CTR. CONCLUSION: Elastic
      artery distensibility and carotid artery IMT are not different in young women
      with extensive endurance training over several years and in those with sedentary
      lifestyle. On the other hand, our data suggest that long-term endurance training
      is associated with potentially favourable peripheral artery adaptation,
      especially in sports where upper body work is added. This adaptation, if
      persisting later in life, could contribute to lower cardiovascular risk.

PMID- 29359514
TI  - Photoluminescence of Visible and NIR-Emitting Lanthanide-Doped Bismuth-Organic
      Materials.
AB  - A bismuth-organic compound containing 2,2':6'2"-terpyridine (terpy) and 2
      thiophenecarboxylate (TC), of the general formula (terpy)Bi(kappa2 -TC)3 ?0.47 H2
      O (BiOM-1), has been synthesized under hydrothermal conditions. Addition of a
      lanthanide nitrate solution to the reaction mixture led to statistical
      replacement of the bismuth centers, and yielded isomorphous lanthanide containing
      compounds Bi1-x Lnx OM-1 (Ln=Nd, Sm, Eu, Tb, Dy, Er, and Yb) that showed bismuth
      and/or ligand sensitized lanthanide-centered emission, and the first example of
      NIR emission from a lanthanide doped BiOM. The structure was determined by single
      crystal X-ray diffraction, and the level and uniformity of lanthanide ion
      incorporation into the bismuth host was determined by ICP-OES and electron
      microprobe analysis. For the visible emitters, lifetime data and quantum yields
      are presented. A high efficiency of sensitization was calculated for the europium
      analog (50.1 %), showing significant improvement over previously reported
      europium thiophenecarboxylates. These novel materials may provide strategies to
      address concerns over the long-term sustainability of the rare earth elements,
      especially relating to optical devices.

PMID- 29359515
TI  - Bone marrow-derived mononuclear cell therapy for nonischaemic dilated
      cardiomyopathy-A meta-analysis.
AB  - OBJECTIVE: The therapeutic effects of bone marrow-derived mononuclear cells
      (BMMNCs) transplantation in patients with nonischaemic dilated cardiomyopathy
      (DCM) are still under debate. Current randomized controlled trials (RCTs)
      reported conflicting results. The aim of this study was to assess the effects of
      BMMNCs transplantation on left ventricular ejection fraction (LVEF) in patients
      with nonischaemic DCM. METHODS: A comprehensive search of PubMed, EMBASE and
      Cochrane Controlled Trials Register was performed. We included RCTs reporting
      data on LVEF in patients with nonischaemic DCM after BMMNCs transplantation.
      RESULTS: Seven RCTs including 463 patients were included. BMMNCs transplantation
      significantly improved LVEF by 3.79% (95% CI: 0.56%-7.03%; P = .007) and LVESV by
      -24.36 mL (95% CI: -46.36 to -2.36 mL; P = .03), while had no impact on the risk
      of all-cause death (OR 0.92; 95% CI: 0.41 to 2.08%; P = .84). Subgroup analysis
      demonstrated a more significant improvement of LVEF in patients with longer
      follow-up (~15 months to 5 years) than shorter ones (12 months). Moreover, using
      bone marrow mononuclear cells was more effective than using G-CSF-stimulated bone
      marrow/peripheral blood stem cells in the improvement of LVEF in patients with
      nonischaemic DCM. CONCLUSIONS: Bone marrow-derived mononuclear cells
      transplantation is associated with a moderate, but significant, improvement in
      LVEF in patients with nonischaemic DCM. This meta-analysis supports further RCT
      conductions using BMMNCs transplantation with larger patient's population and
      longer term follow-up.

PMID- 29359516
TI  - Seminal SIRT1 expression in infertile oligoasthenoteratozoospermic men with
      varicocoele.
AB  - In a case-controlled study, we assessed the expressed seminal NAD-dependent
      protein deacetylase (SIRT1) expression in infertile oligoasthenoteratozoospermic
      (OAT) men associated with varicocoele. Our study involved 81 men, recruited from
      the University hospitals, after ethical approval and informed consent. They were
      allocated into fertile normozoospermic men (n = 23), infertile OAT men without
      varicocoele (n = 23) and infertile OAT men with varicocoele (n = 35). Inclusion
      criteria consisted of confirmation of abnormal semen parameters and normal female
      partners whereas exclusion criteria were leukocytospermia, tobacco smoking,
      hormonal therapy, immunological disorders, dyslipidemia, hypogonadism,
      cardiovascular disorders, morbid obesity, and hepatic or renal failures. All
      participants had an interview to assess clinical history, clinical examination,
      semen analysis, and estimation of seminal SIRT1 expression. Seminal SIRT1
      expression was significantly lower in infertile OAT men than fertile men. Among
      infertile OAT men, seminal SIRT1 expression was significantly lower in those with
      varicocoele than in those without. Additionally, seminal SIRT1 expression was
      significantly lower in varicocoele grade III cases compared with other grades.
      Seminal SIRT1 expression was positively correlated with sperm concentration (r =
      0.327, p = 0.001), total sperm motility (r = 0.532, p = 0.001), and sperm normal
      forms (r = 0.469, p = 0.001). Our results suggest that seminal SIRT1 expression
      has a role of male infertility being significantly decreased in infertile OAT men
      in general and in infertile OAT men associated with varicocoele in particular.

PMID- 29359517
TI  - Fine-needle aspiration of a pancreatic neuroendocrine tumor with prominent
      rhabdoid features.
AB  - Pancreatic neuroendocrine tumors (PanNETs) are uncommon neoplasms that
      conventionally possess architectural and cytomorphological features seen in
      neuroendocrine neoplasms found at other sites. When present, these features often
      allow rapid identification of neuroendocrine differentiation and an accurate
      diagnosis. Here, we report the cytologic findings seen on fine-needle aspiration
      (FNA) of a PanNET with distinct rhabdoid features. This morphology is rare in
      PanNETs and has been reported in only two case series examining surgical
      resection specimens and has not been described on FNA. It is important to
      recognize this morphology as this variant appears to portend an aggressive
      clinical course. Furthermore, unfamiliarity with this morphologic variant may
      lead to a larger initial differential and thus delay final diagnosis.

PMID- 29359518
TI  - Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult
      Brain Subventricular Zone.
AB  - The subventricular zone (SVZ) is the major stem cell niche in the brain of adult
      mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and
      give birth to neurons and glial cells. Previous studies underlined enrichment in
      calcium signaling-related transcripts in adult NSC. Because of their ability to
      mobilize sustained calcium influxes in response to a wide range of extracellular
      factors, store-operated channels (SOC) appear to be, among calcium channels,
      relevant candidates to induce calcium signaling in NSC whose cellular activities
      are continuously adapted to physiological signals from the microenvironment. By
      Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and
      immunocytochemistry experiments, we demonstrate that SVZ cells express molecular
      actors known to build up SOC, namely transient receptor potential canonical 1
      (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1
      (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium
      entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called
      BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ
      stem cell division from symmetric proliferative to asymmetric, thereby reducing
      the stem cell population. Brain section immunostainings show that TRPC1, Orai1,
      and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365
      in brain lateral ventricle diminishes SVZ cell proliferation and reduces the
      ability of SVZ cells to form neurospheres in vitro. The present study combining
      in vitro and in vivo approaches uncovers a major role for SOC in the control of
      SVZ NSC population and opens new fields of investigation for stem cell biology in
      health and disease. Stem Cells 2018;36:761-774.

PMID- 29359519
TI  - Predicting corticosteroid-free endoscopic remission with vedolizumab in
      ulcerative colitis.
AB  - BACKGROUND: Vedolizumab is an effective therapy for ulcerative colitis (UC), but
      costly and slow to work. New clinical responses occur after 30 weeks of therapy.
      AIMS: To enable physicians, patients, and insurers to predict whether a patient
      with UC will respond to vedolizumab at an early time point after starting
      therapy. METHODS: The clinical study data request website provided the phase 3
      clinical trial data for vedolizumab. Random forest models were trained on 70% and
      tested on 30% of the data to predict corticosteroid-free endoscopic remission at
      week 52. Models were constructed using baseline data, or data through week 6 of
      vedolizumab therapy from 491 subjects. RESULTS: The AuROC for prediction of
      corticosteroid-free endoscopic remission at week 52 using baseline data was only
      0.62 (95% CI: 0.53-0.72), but was 0.73 (95% CI: 0.65-0.82) when using data
      through week 6. A total of 47% of subjects were predicted to be remitters, and
      59% of these subjects achieved corticosteroid-free endoscopic remission, in
      contrast to 21% of the predicted non-remitters. A week 6 prediction using FCP
      <=234 MUg/g was nearly as accurate. CONCLUSIONS: A machine learning algorithm
      using laboratory data through week 6 of vedolizumab therapy was able to
      accurately identify which UC patients would achieve corticosteroid-free
      endoscopic remission on vedolizumab at week 52. Application of this algorithm
      could have significant implications for clinical decisions on whom to continue on
      this costly medication when the benefits of the vedolizumab are not clinically
      apparent in the first 6 weeks of therapy.

PMID- 29359520
TI  - National rates, trends and determinants of inpatient surgical management of tubal
      ectopic pregnancy in the United States, 1998-2011.
AB  - AIM: To describe the frequency and temporal trends of inpatient hospitalization
      for tubal ectopic pregnancy as well as patients' characteristics, determinants
      and the current national trends in surgical management of ectopic pregnancy.
      METHODS: We conducted a retrospective, cross-sectional analysis of patients who
      were treated for tubal ectopic pregnancy in an inpatient hospital setting in the
      United States from 1998 to 2011 using data from the Nationwide Inpatient Sample
      databases. National frequency and significant changes in the rate of surgical
      management of tubal ectopic pregnancy in the inpatient setting are described.
      RESULTS: The study included 334 639 tubal ectopic pregnancies for women aged 18
      50 in the United States from 1998 to 2011. The rate of tubal ectopic pregnancy
      (per 10 000 maternal admissions) decreased from 77.2 in 1998 to 40.5 in 2011. The
      proportion of tubal ectopic pregnancies for which salpingostomy was performed
      decreased from 17.0% in 1998 to 7.0% in 2011, while the rate of salpingectomy
      increased from 69.3% in 1998 to 80.9% in 2011. The temporal change in surgical
      choice was not different in states with comprehensive in vitro fertilization
      insurance mandates. CONCLUSION: The rate of tubal ectopic pregnancy managed in
      the inpatient setting in the United States decreased 5% annually between 1998 and
      2011. The rate of salpingectomies performed annually increased whereas that of
      salpingostomy decreased over time. The surgical approach selected for the
      management of tubal ectopic pregnancies was not influenced by a state's in vitro
      fertilization mandate status.

PMID- 29359521
TI  - Neural correlates of lower limbs proprioception: An fMRI study of foot position
      matching.
AB  - Little is known about the neural correlates of lower limbs position sense,
      despite the impact that proprioceptive deficits have on everyday life activities,
      such as posture and gait control. We used fMRI to investigate in 30 healthy right
      handed and right-footed subjects the regional distribution of brain activity
      during position matching tasks performed with the right dominant and the left
      nondominant foot. Along with the brain activation, we assessed the performance
      during both ipsilateral and contralateral matching tasks. Subjects had lower
      errors when matching was performed by the left nondominant foot. The fMRI
      analysis suggested that the significant regions responsible for position sense
      are in the right parietal and frontal cortex, providing a first characterization
      of the neural correlates of foot position matching.

PMID- 29359522
TI  - Use of olmesartan and enteropathy outcomes: a multi-database study.
AB  - BACKGROUND: Multiple case reports suggest that olmesartan may be linked to sprue
      like enteropathy; however, few epidemiological studies have examined this
      association and results have been mixed. AIM: To assess whether olmesartan is
      associated with a higher rate of enteropathy vs other angiotensin II receptor
      blockers (ARBs). METHODS: We conducted a cohort study among ARB initiators in 5
      US claims databases representing different health insurance programmes. Cox
      regression models were used to estimate hazard ratios (HRs) and 95% confidence
      intervals (CIs) for enteropathy-related outcomes, including coeliac disease,
      malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non
      infectious enteropathy, comparing olmesartan initiators to initiators of other
      ARBs after propensity score (PS) matching. RESULTS: We identified 1 928 469
      eligible patients. The unadjusted incidence rates were 0.82, 1.41, 1.66 and 29.20
      per 1000 person-years for coeliac disease, malabsorption, concomitant diagnoses
      of diarrhoea and weight loss, and non-infectious enteropathy respectively. HRs
      after PS matching comparing olmesartan to other ARBs were 1.21 (95% CI, 1.05
      1.40), 1.00 (95% CI, 0.88-1.13), 1.22 (95% CI, 1.10-1.36) and 1.04 (95% CI, 1.01
      1.07) for each outcome. HRs were larger for patients aged 65 years and older (eg
      for coeliac disease, 1.57 [95% CI, 1.20-2.05]), for patients receiving treatment
      for more than 1 year (1.62 [95% CI, 1.24-2.12]), and for patients receiving
      higher cumulative olmesartan doses (1.78 [95% CI, 1.33-2.37]). CONCLUSIONS: This
      large-scale, multi-database study found a higher rate of enteropathy in
      olmesartan initiators as compared to initiators of other ARBs, although the
      absolute incidence rate was low in both groups.

PMID- 29359523
TI  - Kawasaki disease: Epidemiological differences between past and recent periods,
      and implications of distribution dynamism.
AB  - BACKGROUND: Epidemiological findings suggest that Kawasaki disease (KD) is
      mediated by infection, which triggers its onset. Although the mechanism of onset
      seems to involve preconditioning factors and triggering factors, the details
      remain unclarified. METHODS: Data for 330 662 patients reported in KD nationwide
      surveys in Japan implemented between 1961 and 2014 were chronologically compared
      in terms of patient age distribution, estimated mean onset age, and male-to
      female ratio during four periods: pre-epidemic (P1), epidemic (P2), stable (P3),
      and recent (P4): 1961-1978, 1979-1986, 1987-1997, and 1998-2014, respectively.
      RESULTS: During P2, the number of patients aged 6 months-2 years increased, and
      the mean onset age was younger; during P4, however, the number of patients aged
      <=1 year decreased, but the number of patients >=2 years increased, with a flat
      onset age distribution chart, and the mean onset age was older. During P2,
      increases in the number of patients were accompanied by younger mean onset age,
      whereas during P4, increases in the number of patients were conversely
      accompanied by older mean onset ages. The male: female ratio tended to decrease
      during P2, but this tendency was not seen in P4. No outbreak occurred during a
      recent 28 year period (P3, P4). Specific preconditioning factors might have been
      present during the 8 years (P2) of the past three outbreaks. CONCLUSION: P2 and
      P4 were significantly different in epidemiological features. It is likely that
      they do not share the same mechanism of onset (preconditioning and/or trigger
      factors).

PMID- 29359524
TI  - Low Apgar scores at both one and five minutes are associated with long-term
      neurological morbidity.
AB  - AIM: This study evaluated the associations between low Apgar scores at one and
      five minutes and long-term neurological impairments. METHODS: This study used
      population-based data on 399,815 singletons born in Finland in 2004-2010 and
      multivariable logistic regression to examine any associations between low (0-3)
      and intermediate (4-6) Apgar scores and cerebral palsy, epilepsy, intellectual
      disability and sensorineural defects by the age of four years. RESULTS: The odd
      ratios (OR) and 95% confidence intervals (95% CI) showed that low Apgar scores
      were associated with cerebral palsy at one and five minutes (ORs 2.08, 95% CI
      1.32-3.26 and 5.19, 95% CI 3.06-8.80), epilepsy (ORs 1.62, 95% CI 1.13-2.33 and
      4.79, 95% CI 3.03-7.56), and intellectual disability (ORs 2.46, 95% CI 1.45-4.16
      and 6.21, 95% CI 3.33-11.58). Only a low five-minute Apgar score was associated
      with sensorineural defects (OR 3.13, 95% CI 1.95-5.02). Neurological impairment
      risks were increased by low Apgar scores at both one and five minutes (OR 11.1,
      95% CI 8.6-14.5), but 90.3% of children with persistent low Apgar scores had no
      impairment. CONCLUSION: Low one-minute and five-minute Apgar scores were
      associated with long-term neurological morbidity, especially when both scores
      were low.

PMID- 29359525
TI  - The variation in chemical composition of barley feed with or without enzyme
      supplementation influences nutrient digestibility and subsequently affects
      performance in piglets.
AB  - This study investigates the effect of dietary supplementation of a beta-glucanase
      and beta-xylanase enzyme mix to barley based diets, at two different chemical
      compositions achieved through different agronomical conditions on growth
      performance, coefficient of apparent total tract digestibility (CATTD) of
      nutrients, selected faecal microbial populations and faecal scores in piglets.
      Sixty-four piglets (11.7 kg (SD 0.96)) housed in pens of two were assigned to one
      of four dietary treatments (n = 8). The dietary treatments were as follows: (T1)
      low quality barley diet, (T2) low quality barley diet containing a beta-glucanase
      and beta-xylanase enzyme supplement, (T3) high quality barley diet and (T4) high
      quality barley diet containing a beta-glucanase and beta-xylanase enzyme
      supplement. Piglets offered the low quality barley-based diet had a higher (p <
      .05) average daily gain (ADG) (0.73 vs. 0.69 kg, SEM 0.001), gain:feed (G:F)
      ratio (0.61 vs. 0.58 kg, SEM 0.011) and a higher CATTD (p < .001) of dry matter
      (DM), organic matter (OM), nitrogen (N), ash, gross energy (GE) and neutral
      detergent fibre (NDF) compared with piglets offered the high quality barley diet.
      Piglets offered the high quality barley-based diet had reduced faecal scores
      compared to piglets offered the low quality barley-based diet (2.44 vs. 2.57, SEM
      0.036) (p < .05). There was a higher population of Lactobacillus spp. (11.6 vs.
      10.5 log gene copy number/g faeces, SEM 0.177) (p < .001) and total volatile
      fatty acid (VFA) concentration (185 vs. 165 mmol/g faeces, SEM 5.658) (p < .001)
      in the faeces of piglets offered the high quality barley-based diet compared to
      piglets offered the low quality barley-based diet. The inclusion of a beta
      glucanase and beta-xylanase enzyme complex had no effect on any variable
      measured. In conclusion, the higher quality barley-based diet showed beneficial
      effects on the faecal Lactobacillus spp. population and faecal scores of the
      piglets; however, the higher level of beta-glucans in the diet decreased nutrient
      digestibility and subsequently decreased the performance.

PMID- 29359527
TI  - Treatment of premenstrual mood changes in a patient with schizophrenia using
      dienogest: A case report.
AB  - Dienogest is a fourth-generation progestin that is used for the treatment of
      endometriosis. We report a case of premenstrual mood changes in a patient with
      schizophrenia who was unresponsive to conventional treatment but successfully
      managed with dienogest. A 37-year-old Japanese woman with schizophrenia was
      referred to our hospital and diagnosed with premenstrual exacerbation of
      schizophrenia or coexisting premenstrual dysphoric disorder with schizophrenia.
      She had already taken maximal doses of selective serotonin reuptake inhibitors
      and combined oral contraceptives produced intolerable side effects. Gonadotropin
      releasing hormone agonist treatment was effective but was not suitable for long
      term use. Dienogest was initiated to treat pelvic endometriosis and produced
      subsequent improvements in mental status. The patient was able to return to work
      and did not indicate any adverse effects. This case suggests that dienogest may
      be useful for managing premenstrual mood changes in patients with schizophrenia,
      that it can be safely administered over long periods of time.

PMID- 29359528
TI  - Is it time for a more 'proactive' approach to metastatic prostate cancer?

PMID- 29359529
TI  - Examining the role of centralisation of radical cystectomy for bladder cancer.

PMID- 29359530
TI  - Selecting patients for prostate cancer treatment: the role of comorbidity.

PMID- 29359526
TI  - Socioeconomic disadvantage and altered corticostriatal circuitry in urban youth.
AB  - Socioeconomic disadvantage (SED) experienced in early life is linked to a range
      of risk behaviors and diseases. Neuroimaging research indicates that this
      association is mediated by functional changes in corticostriatal reward systems
      that modulate goal-directed behavior, reward evaluation, and affective
      processing. Existing research has focused largely on adults and within-household
      measures as an index of SED, despite evidence that broader community-level SED
      (e.g., neighborhood poverty levels) has significant and sometimes distinct
      effects on development and health outcomes. Here, we test effects of both
      household- and community-level SED on resting-state functional connectivity
      (rsFC) of the ventral striatum (VS) in 100 racially and economically diverse
      children and adolescents (ages 6-17). We observed unique effects of household
      income and community SED on VS circuitry such that higher community SED was
      associated with reduced rsFC between the VS and an anterior region of the medial
      prefrontal cortex (mPFC), whereas lower household income was associated with
      increased rsFC between the VS and the cerebellum, inferior temporal lobe, and
      lateral prefrontal cortex. Lower VS-mPFC rsFC was also associated with higher
      self-reported anxiety symptomology, and rsFC mediated the link between community
      SED and anxiety. These results indicate unique effects of community-level SED on
      corticostriatal reward circuitry that can be detected in early life, which
      carries implications for future interventions and targeted therapies. In
      addition, our findings raise intriguing questions about the distinct pathways
      through which specific sources of SED can affect brain and emotional development.

PMID- 29359531
TI  - The challenge with systematic reviews of non-randomised studies in urology.

PMID- 29359532
TI  - Even 'low-dose' cabazitaxel requires careful and meticulous patient selection.

PMID- 29359533
TI  - The City of Johannesburg can end AIDS by 2030: modelling the impact of achieving
      the Fast-Track targets and what it will take to get there.
AB  - INTRODUCTION: In 2014, city leaders from around the world endorsed the Paris
      Declaration on Fast-Track Cities, pledging to achieve the 2020 and 2030 HIV
      targets championed by UNAIDS. The City of Johannesburg - one of South Africa's
      metropolitan municipalities and also a health district - has over 600,000 people
      living with HIV (PLHIV), more than any other city worldwide. We estimate what it
      would take in terms of programmatic targets and costs for the City of
      Johannesburg to meet the Fast-Track targets, and demonstrate the impact that this
      would have. METHODS: We applied the Optima HIV epidemic and resource allocation
      model to demographic, epidemiological and behavioural data on 26 sub-populations
      in Johannesburg. We used data on programme costs and coverage to produce baseline
      projections. We calculated how many people must be diagnosed, put onto treatment
      and maintained with viral suppression to achieve the 2020 and 2030 targets. We
      also estimated how treatment needs - and therefore fiscal commitments - could be
      reduced if the treatment targets are combined with primary HIV prevention
      interventions (voluntary medical male circumcision (VMMC), an expanded condom
      programme, and comprehensive packages for female sex workers (FSW) and young
      females). RESULTS: If current programmatic coverage were maintained, Johannesburg
      could expect 303,000 new infections and 96,000 AIDS-related deaths between 2017
      and 2030 and 769,000 PLHIV by 2030. Achieving the Fast-Track targets would
      require an additional 135,000 diagnoses and 232,000 people on treatment by 2020
      (an increase in around 80% over 2016 treatment numbers), but would avert 176,000
      infections and 56,500 deaths by 2030. Assuming stable ART unit costs, this would
      require ZAR 29 billion (USD 2.15 billion) in cumulative treatment investments
      over the 14 years to 2030. Plausible scale-ups of other proven interventions
      (VMMC, condom distribution and FSW strategies) could yield additional reductions
      in new infections (between 4 and 15%), and in overall treatment investment needs.
      Scaling up VMMC in line with national targets is found to be cost-effective in
      the medium term. CONCLUSIONS: The scale-up in testing and treatment programmes
      over this decade has been rapid, but these efforts must be doubled to reach 2020
      targets. Strategic investments in proven interventions will help Johannesburg
      achieve the treatment targets and be on track to end AIDS by 2030.

PMID- 29359534
TI  - Altered cortical activation and connectivity patterns for visual attention
      processing in young adults post-traumatic brain injury: A functional near
      infrared spectroscopy study.
AB  - AIMS: This study aimed at understanding the neurobiological mechanisms associated
      with inattention induced by traumatic brain injury (TBI). To eliminate the
      potential confounding caused by the heterogeneity of TBI, we focused on young
      adults postsports-related concussion (SRC). METHODS: Functional near-infrared
      spectroscopy (fNIRS) data were collected from 27 young adults post-SRC and 27
      group-matched normal controls (NCs), while performing a visual sustained
      attention task. Task responsive cortical activation maps and pairwise functional
      connectivity among six regions of interest were constructed for each subject.
      Correlations among the brain imaging measures and clinical measures of attention
      were calculated in each group. RESULTS: Compared to the NCs, the SRC group showed
      significantly increased brain activation in left middle frontal gyrus (MFG) and
      increased functional connectivity between right inferior occipital cortex (IOC)
      bilateral calcarine gyri (CG). The left MFG activation magnitude was
      significantly negatively correlated with the hyperactive/impulsive symptom
      severity measure in the NCs, but not in the patients. The right hemisphere CG-IOC
      functional connectivity showed a significant positive correlation with the
      hyperactive/impulsive symptom severity measure in patients, but not in NCs.
      CONCLUSION: The current data suggest that abnormal left MFG activation and hyper
      communications between right IOC and bilateral CG during visual attention
      processing may significantly contribute to behavioral manifestations of attention
      deficits in patients with TBI.

PMID- 29359536
TI  - Incidence and Seasonal Variation of Distal Radius Fractures in Korea: a
      Population-based Study.
AB  - BACKGROUND: The present study aimed to investigate the incidence and seasonal
      variation of distal radius fractures (DRFs) in Korea. METHODS: We analyzed a
      nationwide database acquired from the Korean Health Insurance Review and
      Assessment Service from 2011 to 2015. We used International Classification of
      Diseases, 10th revision codes and procedure codes to identify patients of all
      ages with newly diagnosed DRFs. RESULTS: An average of about 130,000 DRFs
      occurred annually in Korea. The incidence of DRF, by age group, was highest in
      the 10 to 14-year-old age group for males and the highest in the 70s age group
      for females, with a rapid increase of incidence after 50 years. The peak
      incidence of DRF occurred during winter; however, the incidence greatly varied
      annually when compared with that of other seasons. The incidence of DRFs during
      the winter season was correlated with the average temperature. CONCLUSION: The
      annual incidence of DRF was 130,000 in Korea. The incidence increased under an
      intense cold surge during winter. Active preventive measures are recommended
      especially in women exceeding 50 years considering the higher incidence in this
      age group.

PMID- 29359535
TI  - Trends and Cut-Point Changes in Obesity Parameters by Age Groups Considering
      Metabolic Syndrome.
AB  - BACKGROUND: Non-communicable diseases (NCDs) are an important issue worldwide.
      Obesity has a close relationship with NCDs. Various age-related changes should be
      considered when evaluating obesity. METHODS: National representative cohort data
      from the National Health Insurance Service National Sample Cohort from 2012 to
      2013 were used. Sex-specific and age group-specific (10-year intervals) means for
      body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WtHR)
      were calculated. Optimal cut-points for obesity parameters were defined as the
      value predicting two or more components of metabolic syndrome (except WC).
      RESULTS: The mean value and optimal cut-point for BMI decreased with age for men.
      The mean BMI value for women increased with age, but optimal cut-points showed no
      remarkable difference. The mean WC of men increased with age, but the optimal cut
      points were similar for age groups. For women, the mean value and optimal cut
      point for WC increased with age. Regarding WtHR, the mean value and optimal cut
      point increased with age for men and women. Differences across age groups were
      larger for women. CONCLUSION: The mean values of the obesity indices and the
      optimal cut-points were changed according to age groups. This study supports the
      necessity of applying age group-specific cut-points for the various obesity
      parameters.

PMID- 29359537
TI  - Hospital-based Influenza Morbidity and Mortality (HIMM) Surveillance for A/H7N9
      Influenza Virus Infection in Returning Travelers.
AB  - Since 2013, the Hospital-based Influenza Morbidity and Mortality (HIMM)
      surveillance system began a H7N9 influenza surveillance scheme for returning
      travelers in addition to pre-existing emergency room (ER)-based influenza-like
      illness (ILI) surveillance and severe acute respiratory infection (SARI)
      surveillance. Although limited to eastern China, avian A/H7N9 influenza virus is
      considered to have the highest pandemic potential among currently circulating
      influenza viruses. During the study period between October 1st, 2013 and April
      30th, 2016, 11 cases presented with ILI within seven days of travel return. These
      patients visited China, Hong Kong, or neighboring Southeast Asian countries, but
      none of them visited a livestock market. Seasonal influenza virus (54.5%, 6 among
      11) was the most common cause of ILI among returning travelers, and avian A/H7N9
      influenza virus was not detected during the study period.

PMID- 29359539
TI  - Uveoretinal Adverse Effects Presented during Systemic Anticancer Chemotherapy: a
      10-Year Single Center Experience.
AB  - BACKGROUND: The present study describes our 10-year experience with uveoretinal
      adverse events that manifest because of chemotherapy. METHODS: A retrospective
      chart review was performed for all patients who presented to the ophthalmologic
      department while undergoing systemic chemotherapy between July 2005 and June
      2015. RESULTS: A total of 55 patients (mean age, 51.2 years, 38 women [69.1%])
      suspected of having uveoretinal disease owing to the use of chemotherapeutic
      agents alone were enrolled. Breast cancer was the predominant disease (36.4%);
      noninfectious anterior uveitis (21.8%) was the most common condition. Bilateral
      involvement was observed in 16 patients (29.1%). Although cisplatin (21.8%) was
      the most commonly used drug, daunorubicin, cytarabine, tamoxifen, toremifene, and
      imatinib were also frequently used. The median duration until ophthalmologic
      diagnosis was 208.5 days (range, 19-5,945 days). The proportion of patients with
      final visual acuity (VA) < 20/40 Snellen VA (0.5 decimal VA) was 32.7%. However,
      no relationship was observed between final VA < 20/40 and age, sex, therapeutic
      agents, and metastasis. CONCLUSION: Uveoretinal complications were mostly mild to
      moderate and exhibited a favorable response to conservative therapy. A
      considerable number of patients exhibited significant irreversible loss of vision
      after cessation of the causative chemotherapeutic agent. Ophthalmological
      monitoring is required during chemotherapy.

PMID- 29359538
TI  - Risk of Emergency Operations, Adverse Maternal and Neonatal Outcomes according to
      the Planned Gestational Age for Cesarean Delivery.
AB  - BACKGROUND: The objective of this study was to assess the risk of emergency
      cesarean deliveries (CDs) and adverse neonatal/maternal outcomes according to the
      planned gestational age at delivery (GAD) for elective CD. METHODS: The study
      population consisted of term singleton pregnant women who were booked for
      elective CD and were subsequently delivered at term by CD, after excluding cases
      with a trial of labor. The relationship between the planned GAD, risk of
      emergency CD prior to planned date, and adverse neonatal/maternal outcomes were
      determined. RESULTS: The frequency of emergency CD, adverse neonatal and maternal
      outcomes were 9.5%, 4.5%, and 5.9%, respectively. The risk of emergency CD prior
      to the planned delivery date increased significantly according to the planned GAD
      (5.8% at 37 weeks, 8.2% at 38 weeks, 13.6% at 39 weeks, and 26.7% at 40 weeks or
      more of planned GAD, P = 0.005). Emergency CD was associated with an increased
      risk of adverse maternal outcomes, whereas the risk of adverse neonatal outcomes
      did not differ. In the total study population including both cases with elective
      and emergency CD, the risk of adverse maternal outcomes did not increase
      according to the planned GAD, and the risk of adverse neonatal outcomes decreased
      significantly according to the planned GAD. CONCLUSION: The risk of emergency CD
      increased as the planned GAD increased, but the risk of adverse maternal outcomes
      did not increase and the risk of adverse neonatal outcomes decreased
      significantly according to the planned GAD in the total study population
      including elective/emergency CD.

PMID- 29359541
TI  - The Variations of MER Receptor Tyrosine Kinase and the Development of Chronic
      Obstructive Pulmonary Disease.

PMID- 29359540
TI  - Association between Genetic Variations of MERTK and Chronic Obstructive Pulmonary
      Disease in Koreans.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating lung
      disease. To date, a large number of clinical studies have been conducted to
      investigate the association between genetic variations and COPD. However, little
      is known regarding the genetic susceptibility of Koreans to this disease. MER
      receptor tyrosine kinase (MERTK) plays important roles in the inhibition of
      inflammation and in the clearance of apoptotic cells. Here, we investigated the
      association between genetic variations in MERTK and the development of COPD in
      Koreans. METHODS: We conducted genetic analysis of MERTK using genomic DNA
      samples from 87 patients with COPD and 88 healthy controls and compared the
      frequency of each variation or haplotype between the patient and control groups.
      Subsequently, the effect of each variation was evaluated using in vitro assays.
      RESULTS: Ten variations were identified in this study, four of them for the first
      time. In addition, we found that the frequency of each variation or haplotype was
      comparable between the patient and control groups. However, we observed that the
      frequency for the wild-type haplotype was higher in the control group, compared
      to that in the group of patients with COPD, in the subgroup analysis of current
      smokers, although the difference was not statistically significant (P = 0.080).
      In in vitro assays, we observed that none of the variations affected the activity
      of the promoter or the expression of MERTK. CONCLUSION: Our findings indicate
      that the susceptibility to COPD is not related to the genetic variations or
      haplotypes of MERTK in Koreans.

PMID- 29359542
TI  - Heterotopic Ossification of the Xiphoid Process after Abdominal Surgery for
      Traumatic Hemoperitoneum.
AB  - Heterotopic ossification of the xiphoid process is extremely rare, with only
      three cases previously reported. However, the surgical pathology for
      postoperative elongation of the xiphoid process after abdominal surgery has not
      yet been reported. We report a case of the postoperative elongation of the
      xiphoid process, 8 years after abdominal surgery for traumatic hemoperitoneum in
      a 53-year-old man. The patient underwent surgical excision of the elongated mass
      of the xiphoid process. Histopathology revealed multiple exostoses. Heterotopic
      ossification can occur after surgical trauma to soft or bone tissue. Surgical
      excision with primary closure is the treatment of choice for symptomatic
      heterotopic ossification.

PMID- 29359543
TI  - Letter to the Editor: Genetic Contributions to Childhood Obesity: Association of
      Candidate Gene Polymorphisms and Overweight/Obesity in Korean Preschool Children.

PMID- 29359544
TI  - The Author's Response: Genetic Contributions to Childhood Obesity: Association of
      Candidate Gene Polymorphisms and Overweight/Obesity in Korean Preschool Children.

PMID- 29359545
TI  - Spatially extended versus frontal cerebral near-infrared spectroscopy during
      cardiac surgery: a case series identifying potential advantages.
AB  - Stroke due to hypoperfusion or emboli is a devastating adverse event of cardiac
      surgery, but early detection and treatment could protect patients from an
      unfavorable postoperative course. Hypoperfusion and emboli can be detected with
      transcranial Doppler of the middle cerebral artery (MCA). The measured blood flow
      velocity correlates with cerebral oxygenation determined clinically by near
      infrared spectroscopy (NIRS) of the frontal cortex. We tested the potential
      advantage of a spatially extended NIRS in detecting critical events in three
      cardiac surgery patients with a whole-head fiber holder of the FOIRE-3000
      continuous-wave NIRS system. Principle components analysis was performed to
      differentiate between global and localized hypoperfusion or ischemic territories
      of the middle and anterior cerebral arteries. In one patient, we detected a
      critical hypoperfusion of the right MCA, which was not apparent in the frontal
      channels but was accompanied by intra- and postoperative neurological correlates
      of ischemia. We conclude that spatially extended NIRS of temporal and parietal
      vascular territories could improve the detection of critically low cerebral
      perfusion. Even in severe hemispheric stroke, NIRS of the frontal lobe may remain
      normal because the anterior cerebral artery can be supplied by the contralateral
      side directly or via the anterior communicating artery.

PMID- 29359547
TI  - Functional Layer-by-Layer Thin Films of Inducible Nitric Oxide (NO) Synthase
      Oxygenase and Polyethylenimine: Modulation of Enzyme Loading and NO-Release
      Activity.
AB  - Nitric oxide (NO) release counteracts platelet aggregation and prevents the
      thrombosis cascade in the inner walls of blood vessels. NO-release coatings also
      prevent thrombus formation on the surface of blood-contacting medical devices.
      Our previous work has shown that inducible nitric oxide synthase (iNOS) films
      release NO fluxes upon enzymatic conversion of the substrate l-arginine. In this
      work, we report on the modulation of enzyme loading in layer-by-layer (LbL) thin
      films of inducible nitric oxide synthase oxygenase (iNOSoxy) on polyethylenimine
      (PEI). The layer of iNOSoxy is electrostatically adsorbed onto the PEI layer. The
      pH of the iNOSoxy solution affects the amount of enzyme adsorbed. The overall
      negative surface charge of iNOSoxy in solution depends on the pH and hence
      determines the density of adsorbed protein on the positively charged PEI layer.
      We used buffered iNOSoxy solutions adjusted to pHs 8.6 and 7.0, while saline PEI
      solution was used at pH 7.0. Atomic force microscopy imaging of the outermost
      layer shows higher protein adsorption with iNOSoxy at pH 8.6 than with a solution
      of iNOSoxy at pH 7.0. Graphite electrodes with PEI/iNOSoxy films show higher
      catalytic currents for nitric oxide reduction mediated by iNOSoxy. The higher
      enzyme loading translates into higher NO flux when the enzyme-modified surface is
      exposed to a solution containing the substrate and a source of electrons.
      Spectrophotometric assays showed higher NO fluxes with iNOSoxy/PEI films built at
      pH 8.6 than with films built at pH 7.0. Fourier transform infrared analysis of
      iNOSoxy adsorbed on PEI at pH 8.6 and 7.0 shows structural differences of iNOSoxy
      in films, which explains the observed changes in enzymatic activity. Our findings
      show that pH provides a strategy to optimize the NOS loading and enzyme activity
      in NOS-based LbL thin films, which enables improved NO release with minimum
      layers of PEI/NOS.

PMID- 29359548
TI  - Separation of PEGylated Gold Nanoparticles by Micellar Enhanced Electrospun Fiber
      Based Ultrathin Layer Chromatography.
AB  - Gold nanoparticles (AuNPs) are of great interest in many fields, especially in
      biomedical applications. Thiol terminated polyethylene glycol (PEG) is the most
      widely used polymer to increase the biocompatibility of nanoparticle
      therapeutics. Herein, a rapid method for separation and characterization of
      PEGylated AuNPs on an ultrathin layer chromatographic (UTLC) plate using
      electrospun polyacrylonitrile (PAN) nanofibers as the stationary phase is
      described. AuNPs with sizes ranging from 10 to 80 and 30 nm AuNPs coated with
      various molecular weight of PEG (2, 5, 10, and 20 kDa) were all successfully
      separated by UTLC using optimized conditions. The fabrication of electrospun UTLC
      is simple, fast, and inexpensive. The UTLC, with much thinner sorbent layer (10*
      thinner than traditional TLC) and small fiber size (~300 nm), requires minimal
      mobile phase solvent and provides faster separation and higher resolution
      compared to other separation methods for AuNPs. AuNPs with different sizes and
      different PEG molecular weights were well separated within 5 min with lowest
      plate height <2 MUm and resolution value >1.5. As an example of this method, the
      size transformation of AuNPs in serum protein was determined quantitatively.

PMID- 29359549
TI  - Robust Anticancer Efficacy of a Biologically Synthesized Tumor Acidity-Responsive
      and Autophagy-Inducing Functional Beclin 1.
AB  - As a potent autophagy inducer, Beclin 1 is essential for the initiation of
      autophagic cell death, and triggering extensive autophagy by targeted delivery of
      Beclin 1 to tumors has enormous potential to inhibit tumor growth. Yet, the
      therapeutic application of Beclin 1 is hampered by its inability to internalize
      into cells and nonselective biodistribution in vivo. To tackle this challenge, we
      employed a novel Beclin 1 delivery manner by constructing a functional protein
      (Trx-pHLIP-Beclin 1, TpB) composed of a thioredoxin (Trx) tag, a pH low insertion
      peptide (pHLIP), and an evolutionarily conserved motif of Beclin 1. This protein
      could effectively transport Beclin 1 to breast and ovarian cancer cell lines
      under weakly acidic conditions (pH 6.5), markedly inhibit tumor cell growth and
      proliferation, and induce obvious autophagy. Furthermore, the in vivo antitumor
      efficacy of the functional Beclin 1 against an SKOV3 xenograft tumor mouse model
      was tested via intravenous injection. TpB preferentially accumulated in tumors
      and exhibited a significantly higher tumor growth inhibition than the nontargeted
      Beclin 1 control, whereas no overt side effects were observed. Taken together,
      this study sheds light on the potential application of TpB as a highly efficient
      yet safe antitumor agent for cancer treatment.

PMID- 29359550
TI  - Synthesis of Polyynes Using Dicobalt Masking Groups.
AB  - Extended triisopropylsilyl end-capped polyynes have been prepared from the
      corresponding tetracobalt complexes by removing the complexed dicobalt
      tetracarbonyldiphenylphosphinomethane (Co2(CO)4dppm) moieties. Unmasking of this
      "masked alkyne equivalent" was achieved under mild conditions with elemental
      iodine at room temperature, making it possible to obtain fragile polyynes with up
      to 20 contiguous sp-hybridized carbon atoms. The Co2(CO)4dppm moiety has a strong
      geometric and steric effect on the polyyne but does not have a marked electronic
      effect on the terminal alkyne, as indicated by NMR and IR spectroscopy, density
      functional theory calculations, and X-ray crystallography. An unusual "alkyne
      hopping" migration of the dicobalt group was noticed as a minor side reaction
      during copper-catalyzed Eglinton coupling.

PMID- 29359551
TI  - Degradable NIR-PTT Nanoagents with a Potential Cu@Cu2O@Polymer Structure.
AB  - Cu@Cu2O@PSMA polymer nanoparticles (Cu@Cu2O@polymer NPs) with near-infrared (NIR)
      absorption were successfully synthesized in a single-step oxidation reaction of
      Cu@PSMA polymer NPs at 100  degrees C for 20 min. The shape, structure, and
      optical properties of the Cu@Cu2O@polymer NPs were tailorable by controlling the
      reaction parameters, for example, using the initial Cu@PSMA polymer NP as a
      template and varying the halide ion content, heating temperature, and reaction
      time. The Cu@Cu2O@polymer NPs exhibited robust NIR absorption between 650 and 710
      nm and possessed superior oxidation resistance in water and culture media. In
      vitro assays demonstrated the low cytotoxicity of the Cu@Cu2O@PSMA polymer NPs to
      HeLa cells through an improved cell viability, high IC50, low injury incidence
      from the supernatant of the partly dissociated Cu@Cu2O@PSMA polymer NPs, and
      minor generation of reactive oxygen species. More importantly, we demonstrated
      that the inorganic Cu-based nanocomposite [+0.34 V vs normal hydrogen electrode
      (NHE)] was degradable in an endogenous H2O2 (+1.78 V vs NHE) environment. Cu ions
      were detected in the urine of mice, which illustrates the possibility of
      extraction after the degradation of the Cu-based particles. 'After an treatment
      of the HeLa cells with the Cu@Cu2O@polymer NPs and a 660 nm light-emitting diode,
      the photoablation of 50 and 90% cells was observed at NP doses of 20 and 50 ppm,
      respectively. These results demonstrate that NIR-functional and moderate redox
      active Cu@Cu2O@polymer NPs are potential next-generation photothermal therapy
      (PTT) nanoagents because of combined features of degradation resistance in the
      physiological environment, enabling the delivery of efficient PTT, a possibly
      improved ability to selectively harm cancer cells by releasing Cu ions under high
      H2O2 and/or low-pH conditions, and ability to be extracted from the body after
      biodegradation.

PMID- 29359552
TI  - Polycyclic Aromatic N-Ethoxycarbonyl Thioamide S-Oxides and Their Triflic Acid
      Promoted Cyclization to Fluorescent Thiophene Imine-Fused Arenes.
AB  - We present the synthesis of a series of polycyclic aromatic-N
      ethoxycarbonylthioamide S-oxides and their triflic acid-promoted cyclization to
      thiophene imine-fused arenes having 2H-naphtho[1,8-bc]thiophen-2-imine, 3H
      pyreno[10,1-bc]thiophen-3-imine, 4H-pyreno[1,10-bc]thiophen-4-imine, 3H
      pyreno[10,1-bc]thiophen-3-imine, 4H-pyreno[1,10-bc]thiophen-3-imine, 3H
      pyreno[10,1-bc]thiophen-3-imine, and 4H-peryleno[3,4-bc]thiophen-4-imine cores.
      The proposed reaction mechanism involves the intermediacy of a novel type of
      electrophilic sulfur species, namely protonated iminosulfenic acid or
      iminosulfenium cations. These species may attack the peri- or ipso-position of
      the arene, leading in some cases to regioisomeric products. The reaction affords
      in high yields novel polycyclic fluorophores emitting in the range of 500-606 nm
      with quantum yields of 0.025-0.64. Comparison with the parent arenes reveals that
      the fused iminothiophene moiety brings about significant bathochromic shifts of
      the absorption and emission bands.

PMID- 29359553
TI  - Tetraphenylphosphonium Bromide as a Cathode Buffer Layer Material for Highly
      Efficient Polymer Solar Cells.
AB  - Here, we introduced the role of small organic molecule tetraphenylphosphonium
      bromide (QPhPBr) as an electron-transporting layer (ETL) material for fabricating
      high-efficiency bulk heterojunction polymer solar cells (PSCs). Their
      significantly higher power conversion efficiency (PCE) in well-known active layer
      devices (PTB7-Th:PC71BM, PBDTTT-CT:PC71BM, and P3HT:PC71BM) was observed compared
      to that of the bare Al cathode. The use of N719 as an ETL was also demonstrated.
      Observed data reveal that QPhPBr-based devices exhibit high PCEs up to 9.18,
      8.42, and 4.81% from PTB7-Th, PBDTTT-CT, and P3HT, respectively. For comparisons,
      the bare Al devices show PCEs of 5.37, 4.75, and 3.01%, respectively. Moreover,
      further enhancement of PSC efficiency (9.83, 8.69, and 5.35%) is achieved from
      mixed binary solution of N719:QPhPBr because of modulated adjustment of the work
      function of the Al electrode. Our results indicate the excellent function of
      tetraphenylphosphonium bromide and its binary blend as effective small-molecule
      organic materials to regulate the metal surface properties and the potential used
      as excellent cathode buffer layer materials for realizing high-efficiency PSCs.

PMID- 29359554
TI  - Metabolomics Reveals that Dietary Ferulic Acid and Quercetin Modulate Metabolic
      Homeostasis in Rats.
AB  - Phenolic compounds ingestion has been shown to have potential preventive and
      therapeutic effects against various metabolic diseases such as obesity and
      cancer. To provide a better understanding of these potential benefit effects, we
      investigated the metabolic alterations in urine and feces of rat ingested ferulic
      acid (FA) and quercetin (Qu) using NMR-based metabolomics approach. Our results
      suggested that dietary FA and/or Qu significantly decreased short chain fatty
      acids and elevated oligosaccharides in the feces, implying that dietary FA and Qu
      may modulate gut microbial community with inhibition of bacterial fermentation of
      dietary fibers. We also found that dietary FA and/or Qu regulated several host
      metabolic pathways including TCA cycle and energy metabolism, bile acid, amino
      acid, and nucleic acid metabolism. These biological effects suggest that FA and
      Qu display outstanding bioavailability and bioactivity and could be used for
      treatment of some metabolic syndromes, such as inflammatory bowel diseases and
      obesity.

PMID- 29359555
TI  - Correction to "Relative Reactivities of Hydroxyl Groups in Carbohydrate
      Derivatives. Specific Nuclear Magnetic Resonance Spectral Assignments of Acetyl
      Groups in Methyl alpha-d-Glucopyranoside Tetraacetate and Related Derivatives".

PMID- 29359557
TI  - Inline Coupling of Electrokinetic Preconcentration Method to Taylor Dispersion
      Analysis for Size-Based Characterization of Low-UV-Absorbing Nanoparticles.
AB  - The inline coupling of the field-amplified sample injection (FASI) to Taylor
      dispersion analysis (TDA) was used to characterize low-UV absorbing carboxylated
      silica nanoparticles (cNPs). The hydrodynamic diameters (Dh) were measured by
      using a commercial capillary electrophoresis instrument. The proposed methodology
      did not require any complicated instruments or chromophoric dye to increase the
      detection sensitivity. A practical method based on a half-Gaussian fitting was
      proposed for the data processing. The results obtained by this method were
      compared with those derived from dynamic light scattering (DLS) and transmission
      electron microscopy (TEM) analyses. From these results, it appeared that the size
      derived by TDA is in excellent agreement with those measured by DLS and TEM, as
      demonstrated by stable nanoparticles with narrow size distributions. Intermediate
      precision relative standard deviations less than 5% were obtained by FASI-TDA.
      The effect of the FASI-induced cNP peak dispersion on the reliability of the
      results was discussed in detail.

PMID- 29359556
TI  - Linoleic Acid:Dihomo-gamma-Linolenic Acid Ratio Predicts the Efficacy of Zn
      Biofortified Wheat in Chicken (Gallus gallus).
AB  - The amount of Zn absorbed from Zn-biofortified wheat material has been determined
      using an in vivo model of Zn absorption. The erythrocyte linoleic:dihomo -gamma
      linolenic acid (LA:DGLA) ratio was used as a biomarker of Zn status. Two groups
      of chickens (n = 15) were fed different diets: a high-Zn (46.5 MUg Zn g-1) and a
      low-Zn wheat-based diet (32.8 MUg Zn g-1). Dietary Zn intakes, body weight, serum
      Zn, and the erythrocyte fatty acid profile were measured, and tissues were taken
      for gene expression analysis. Serum Zn concentrations were greater in the high Zn
      group (p < 0.05). Duodenal mRNA expression of various Zn transporters
      demonstrated expression upregulation in the birds fed a low Zn diet (n = 15, p <
      0.05). The LA:DGLA ratio was higher in the birds fed the low Zn diet (p < 0.05).
      The higher amount of Zn in the biofortified wheat resulted in a greater Zn
      uptake.

PMID- 29359558
TI  - Insulin Detection Using a Corona Phase Molecular Recognition Site on Single
      Walled Carbon Nanotubes.
AB  - Corona phase molecular recognition (CoPhMoRe) is a technique whereby an external,
      adsorbed phase around a colloidal nanoparticle is selected such that its
      molecular conformation or interaction recognizes a specific target analyte. In
      this work, we employ a high-throughput screening of a library of poly(ethylene
      glycol) (PEG)-conjugated lipids adsorbed onto near-infrared fluorescent single
      walled carbon nanotubes to discover a corona phase selective for insulin. We find
      that a C16-PEG(2000 Da)-ceramide causes a 62% fluorescent intensity decrease of
      the (10,2) chirality nanotube in the presence of 20 MUg/mL insulin. The insulin
      protein has no prior affinity toward the C16-PEG(2000 Da)-ceramide molecules in
      free solution, verified by isothermal titration calorimetry, and the interaction
      occurs only upon their adsorption onto the single-walled carbon nanotube
      scaffolds. Testing a panel of proteins originating from human blood as well as
      short 7 amino acid fragments of the insulin peptide rules out nonselective
      recognition mechanisms such as molecular weight, isoelectric point, and
      hydrophobicity-based detection. Interestingly, longer fragments of isolated alpha
      and beta-peptide chains of insulin are detected by the construct, albeit with
      lower affinity compared to that of the intact insulin protein, suggesting that
      the construct recognizes insulin in its native form and conformation. Finally,
      the insulin recognition and the quantification of its solution concentration were
      demonstrated both in buffer and in blood serum, showing that the CoPhMoRe
      construct works in this complex environment despite the presence of potential
      nonspecific adsorption. Our results further motivate the search for nonbiological
      synthetic recognition sites and open up a new path for continuous insulin
      monitoring in vivo with the hope of improving glycemic control in closed-loop
      artificial pancreas systems.

PMID- 29359559
TI  - Phonon Scattering and Electron Doping by 2D Structural Defects in In/ZnO.
AB  - In/ZnO bulk compounds have been synthesized using a simple solid-state process.
      In this study, both the structural features and thermoelectric properties of the
      Zn1-xInxO series with ultralow indium content (0 <= x <= 0.02) have been studied.
      High-angle annular dark-field scanning transmission electron microscopy analyses
      highlight that indium has the ability to create multiple basal plane and
      pyramidal defects that produce ZnO domains with inverted polarity starting from
      dopant concentrations as low as 0.25 atom %. Interestingly, the formation of
      parallel inversion boundaries consisting of InO6 octahedra in the ZnO4 tetrahedra
      matrix is responsible for phonon scattering while increasing electrical
      conductivity, thereby enhancing the thermoelectric properties. This effect of
      multiple extended two-dimensional defects on the thermoelectric properties of ZnO
      is reported for the first time with such low indium doping. On the chemistry
      side, the present results point toward a lack of In solubility in the ZnO
      structure. Moreover, this study is a step forward to the synthesis of other
      thermoelectric compounds where dopant-induced planar defects in bulk transition
      metal compounds have the potential to enhance both phonon scattering and
      electronic conductivity.

PMID- 29359560
TI  - Cycloaddition Reactions of Azomethine Ylides and 1,3-Dienes on the C2v
      Symmetrical Pentakisadduct of C60.
AB  - The reactivity of the C2v-symmetric pentakisadduct of C60 with azomethine ylides
      and conjugated dienes was studied experimentally and computationally. This
      derivative possesses four [6,6] double bonds, each with unique electrophilicity.
      The Diels-Alder reaction studied is a regiospecific, kinetically and
      thermodynamically guided [4 + 2] process producing [5:1]-hexaadducts with an
      octahedral addition pattern. The kinetically controlled Prato reaction gives a
      mixture of regioisomeric [5:1]-hexaadducts. The synthesis of geometrically well
      defined supramolecular architectures may benefit from these new types of highly
      functionalized [5:1]-hexaadducts.

PMID- 29359561
TI  - Synthesis of Fullerotetrahydroquinolines via [4 + 2] Cycloaddition Reaction of
      [60]Fullerene with in Situ Generated Aza-o-quinone Methides.
AB  - An efficient [4 + 2] cycloaddition reaction of [60]fullerene with the in situ
      generated aza-o-quinone methides from N-(o-chloromethyl)aryl sulfonamides with
      the assistance of Cu2O has been developed to afford a series of
      fullerotetrahydroquinolines. This strategy exhibits a broad substrate scope and
      excellent functional group tolerance. A tentative reaction pathway for the
      formation of fullerotetrahydroquinolines is proposed on the basis of the
      experimental results.

PMID- 29359562
TI  - Enhanced Doubly Activated Dual Emission Fluorescent Probes for Selective Imaging
      of Glutathione or Cysteine in Living Systems.
AB  - The development of novel fluorescent probes for monitoring the concentration of
      various biomolecules in living systems has great potential for eventual early
      diagnosis and disease intervention. Selective detection of competitive species in
      biological systems is a great challenge for the design and development of
      fluorescent probes. To improve on the design of fluorescent coumarin-based
      biothiol sensing technologies, we have developed herein an enhanced dual emission
      doubly activated system (DACP-1 and the closely related DACP-2) for the selective
      detection of glutathione (GSH) through the use of one optical channel and the
      detection of cysteine (Cys) by another channel. A phenylselenium group present at
      the 4-position completely quenches the fluorescence of the probe via photoinduced
      electron transfer to give a nonfluorescent species. Probes are selective for
      glutathione (GSH) in the red region and for cysteine/homocysteine (Cys/Hcy) in
      the green region. When they were treated with GSH, DACP-1 and DACP-2 showed
      strong fluorescence enhancement in comparison to that for closely related species
      such as amino acids, including Cys/Hcy. Fluorescence quantum yields (PhiF)
      increased for the red channel (<0.001 to 0.52 (DACP-1) and 0.48 (DACP-2)) and
      green channel (Cys) (<0.001 to 0.030 (DACP-1) and 0.026 (DACP-2)), respectively.
      Competing fluorescent enhancements upon addition of closely related species were
      negligible. Fast responses, improved water solubility, and good cell membrane
      permeability were all properly established with the use of DACP-1 and DACP-2.
      Live human lung cancer cells and fibroblasts imaged by confocal microscopy, as
      well as live mice tumor model imaging, confirmed selective detection.

PMID- 29359563
TI  - Molecular Dynamics Study of Combustion Reactions in a Supercritical Environment.
      Part 2: Boxed MD Study of CO + OH -> CO2 + H Reaction Kinetics.
AB  - Oxy-fuel combustion technology holds a great promise in both increasing the
      efficiency of the energy conversion and reducing environmental impact. However,
      effects of the higher pressures and replacement of the nitrogen with carbon
      dioxide diluent are not well understood at present. The title reaction is one of
      the most important processes in combustion. Despite numerous studies, the effects
      of supercritical carbon dioxide environment did not receive much attention in the
      past. Here we report the results of boxed molecular dynamics simulations of these
      effects at QM/MM theory level with periodical boundary conditions. The free
      energy barriers for HOCO intermediate formation and decomposition were tabulated
      in a wide range of pressures (1-1000 atm) and temperatures (400-1600 K). Pressure
      dependence of calculated rate constants for these reaction steps and overall
      reaction were analyzed. We found that the CO2 environment may increase these rate
      constants up to a factor of 25, at near critical conditions. At higher
      temperatures, this effect weakens significantly. Numerical values for parameters
      of extended Arrhenius equation, suitable for combustion kinetic modeling are
      reported.

PMID- 29359564
TI  - Fluorometric Sniff-Cam (Gas-Imaging System) Utilizing Alcohol Dehydrogenase for
      Imaging Concentration Distribution of Acetaldehyde in Breath and Transdermal
      Vapor after Drinking.
AB  - Understanding concentration distributions, release sites, and release dynamics of
      volatile organic compounds (VOCs) from the human is expected to lead to methods
      for noninvasive disease screening and assessment of metabolisms. In this study,
      we developed a visualization system (sniff-cam) that enabled one to identify a
      spatiotemporal change of gaseous acetaldehyde (AcH) in real-time. AcH sniff-cam
      was composed of a camera, a UV-LED array sheet, and an alcohol dehydrogenase
      (ADH)-immobilized mesh. A reverse reaction of ADH was employed for detection of
      gaseous AcH where a relationship between fluorescence intensity from nicotinamide
      adenine dinucleotide and the concentration of AcH was inversely proportional;
      thus, the concentration distribution of AcH was measured by detecting the
      fluorescence decrease. Moreover, the image differentiation method that calculated
      a fluorescence change rate was employed to visualize a real-time change in the
      concentration distribution of AcH. The dynamic range of the sniff-cam was 0.1-10
      ppm which encompassed breath AcH concentrations after drinking. Finally, the
      sniff-cam achieved the visualization of the concentration distribution of AcH in
      breath and skin gas. A clear difference of breath AcH concentration was observed
      between aldehyde dehydrogenase type 2 active and inactive subjects, which was
      attributed to metabolic capacities of AcH. AcH in skin gas showed a similar time
      course of AcH concentration to the breath and a variety of release concentration
      distribution. Using different NADH-dependent dehydrogenases in the sniff-cam
      could lead to a versatile method for noninvasive disease screening by acquiring
      spatiotemporal information on various VOCs in breath or skin gas.

PMID- 29359565
TI  - Discovery of the First Potent, Selective, and Orally Bioavailable Signal Peptide
      Peptidase-Like 2a (SPPL2a) Inhibitor Displaying Pronounced Immunomodulatory
      Effects In Vivo.
AB  - Signal peptide peptidase-like 2a (SPPL2a) is an aspartic intramembrane protease
      which has recently been shown to play an important role in the development and
      function of antigen presenting cells such as B lymphocytes and dendritic cells.
      In this paper, we describe the discovery of the first selective and orally active
      SPPL2a inhibitor (S)-2-cyclopropyl-N1-((S)-5,11-dioxo-10,11-dihydro-1H,3H,5H
      spiro[benzo[d]pyrazolo[1,2-a][1,2]diazepine-2,1'-cyclopropan]-10-yl)-N4-(5-fluoro
      2-methylpyridin-3-yl)succinamide 40 (SPL-707). This compound shows adequate
      selectivity against the closely related enzymes gamma-secretase and SPP and a
      good pharmacokinetic profile in mouse and rat. Compound 40 significantly
      inhibited processing of the SPPL2a substrate CD74/p8 fragment in rodents at doses
      <=10 mg/kg b.i.d. po. Oral dosing of 40 for 11 days at >=10 mg/kg b.i.d.
      recapitulated the phenotype seen in Sppl2a knockout (ko) and ENU mutant mice
      (reduced number of specific B cells and myeloid dendritic cells). Thus, we
      believe that SPPL2a represents an interesting and druggable pharmacological
      target, potentially providing a novel approach for the treatment of autoimmune
      diseases by targeting B cells and dendritic cells.

PMID- 29359566
TI  - Complex Terahertz and Direct Current Inverse Spin Hall Effect in YIG/Cu1-xIrx
      Bilayers Across a Wide Concentration Range.
AB  - We measure the inverse spin Hall effect of Cu1-xIrx thin films on yttrium iron
      garnet over a wide range of Ir concentrations (0.05 ? x ? 0.7). Spin currents are
      triggered through the spin Seebeck effect, either by a continuous (dc)
      temperature gradient or by ultrafast optical heating of the metal layer. The spin
      Hall current is detected by electrical contacts or measurement of the emitted
      terahertz radiation. With both approaches, we reveal the same Ir concentration
      dependence that follows a novel complex, nonmonotonous behavior as compared to
      previous studies. For small Ir concentrations a signal minimum is observed,
      whereas a pronounced maximum appears near the equiatomic composition. We identify
      this behavior as originating from the interplay of different spin Hall mechanisms
      as well as a concentration-dependent variation of the integrated spin current
      density in Cu1-xIrx. The coinciding results obtained for dc and ultrafast stimuli
      provide further support that the spin Seebeck effect extends to terahertz
      frequencies, thus enabling a transfer of established spintronic measurement
      schemes into the terahertz regime. Our findings also show that the studied
      material allows for efficient spin-to-charge conversion even on ultrafast time
      scales.

PMID- 29359567
TI  - Arynes in the Monoarylation of Unprotected Carbohydrate Amines.
AB  - A CsF-mediated method has been developed for the N-arylation of amino sugars that
      affords good to excellent yields of arylated products under mild conditions
      involving the in situ generation of arynes. The reaction conditions tolerate a
      variety of common carbohydrate protecting groups and also performs exceptionally
      well on unprotected amino sugar derivatives. The reactions are scalable in
      moderate to good yields with broad scope.

PMID- 29359568
TI  - The prognostic analysis of different metastatic patterns in extensive-stage small
      cell lung cancer patients: a large population-based study.
AB  - AIM: To analyze the metastasis patterns and prognosis differences for extensive
      stage small-cell lung cancer patients. METHODS: Log-rank tests were used to
      calculate and compare survival estimates. Cox regression analyses were used to
      evaluate the prognosis factors. RESULTS: The liver was the most common metastatic
      site, and lung was the least common. In two metastatic sites, liver and bone
      metastases were the most common combination of sites. An isolated liver
      metastasis had the worst overall survival (OS) and cancer-specific survival (CSS)
      among metastatic sites (both p < 0.001). Liver and lung metastases were
      associated with worse CSS (p < 0.039) and OS (p < 0.015). However, for patients
      with three metastatic sites showed no statistical differences in their CSS and OS
      (all, p > 0.05). CONCLUSION: Extensive-stage small-cell lung cancer patients with
      metastasis to the liver alone or in combination with other organs appear to have
      worse outcomes.

PMID- 29359569
TI  - Static metrics of impact for a dynamic problem: The need for smarter tools to
      guide suicide prevention planning and investment.
AB  - OBJECTIVES: This study investigates two approaches to estimate the potential
      impact of a population-level intervention on Australian suicide, to highlight the
      importance of selecting appropriate analytic approaches for informing evidence
      based strategies for suicide prevention. METHODS: The potential impact of a
      psychosocial therapy intervention on the incidence of suicide in Australia over
      the next 10 years was used as a case study to compare the potential impact on
      suicides averted using: (1) a traditional epidemiological measure of population
      attributable risk and (2) a dynamic measure of population impact based on a
      systems science model of suicide that incorporates changes over time. RESULTS:
      Based on the population preventive fraction, findings suggest that the
      psychosocial therapy intervention if implemented among all eligible individuals
      in the Australian population would prevent 5.4% of suicides (or 1936 suicides)
      over the next 10 years. In comparison, estimates from the dynamic simulation
      model which accounts for changes in the effect size of the intervention over
      time, the time taken for the intervention to have an impact in the population,
      and likely barriers to the uptake and availability of services suggest that the
      intervention would avert a lower proportion of suicides (between 0.4% and 0.5%)
      over the same follow-up period. CONCLUSION: Traditional epidemiological measures
      used to estimate population health burden have several limitations that are often
      understated and can lead to unrealistic expectations of the potential impact of
      evidence-based interventions in real-world settings. This study highlights these
      limitations and proposes an alternative analytic approach to guide policy and
      practice decisions to achieve reductions in Australian suicide.

PMID- 29359570
TI  - Warning of cancer by the sensation of octopus tentacles in the mouth.

PMID- 29359571
TI  - Strangulated child's psychological trauma intervened with imagery-based cognitive
      therapy.

PMID- 29359572
TI  - 2-year follow-up: Still keeping the body in mind.

PMID- 29359573
TI  - Hydrochloric Acid Infusion for the Treatment of Metabolic Alkalosis in Surgical
      Intensive Care Unit Patients.
AB  - BACKGROUND: Older reports of use of hydrochloric acid (HCl) infusions for
      treatment of metabolic alkalosis document variable dosing strategies and risk.
      OBJECTIVES: This study sought to characterize use of HCl infusions in surgical
      intensive care unit patients for the treatment of metabolic alkalosis. METHODS:
      This retrospective review included patients who received a HCl infusion for >8
      hours. The primary end point was to evaluate the utility of common acid-base
      equations for predicting HCl dose requirements. Secondary end points evaluated
      adverse effects, efficacy, duration of therapy, and total HCl dose needed to
      correct metabolic alkalosis. Data on demographics, potential causes of metabolic
      alkalosis, fluid volume, and duration of diuretics as well as laboratory data
      were collected. RESULTS: A total of 30 patients were included, and the average
      HCl infusion rate was 10.5 +/- 3.7 mEq/h for an average of 29 +/- 14.6 hours.
      Metabolic alkalosis was primarily diuretic-induced (n = 26). Efficacy was
      characterized by reduction in the median total serum CO2 from 34 to 27 mM/L ( P <
      0.001). The change in chloride ion deficit and change in apparent strong ion
      difference (SIDa) were not correlated with total HCl administered. There were no
      documented serious adverse effects related to HCl infusions. CONCLUSION: HCl was
      effective for treating metabolic alkalosis, and no serious adverse events were
      seen. In this clinical setting, the baseline chloride ion deficit and SIDa were
      not useful for prediction of total HCl dose requirement, and serial monitoring of
      response is recommended.

PMID- 29359574
TI  - Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo
      obstruction, or Refractory Constipation.
AB  - BACKGROUND: Neostigmine is traditionally administered intravenously for treatment
      of acute colonic pseudo-obstruction (ACPO), though use is associated with
      administration constraints and adverse effects. OBJECTIVE: To evaluate whether an
      alternative route of administration for neostigmine via subcutaneous (SQ)
      delivery is safe and effective in a broad cohort of medical and surgical
      patients. METHODS: This multicenter, retrospective observational study included
      adult patients administered SQ neostigmine for ileus, ACPO, or refractory
      constipation. Efficacy indicators were time to first bowel movement (BM)
      following initiation of the medication, total SQ neostigmine dose administered to
      produce a BM, and administration of a rescue intervention to produce a BM. Safety
      events evaluated were cardiac arrest, bradycardia, bronchospasm requiring
      intervention, nausea requiring intervention, or severe salivation, lacrimation,
      or diarrhea. RESULTS: A total of 182 patients were eligible for inclusion. The
      most commonly utilized dosing strategy of neostigmine was 0.25 mg SQ 4 times
      daily. The median time to first BM following initiation of SQ neostigmine was
      29.19 hours (interquartile range = 12.18-56.84) with a median dose administered
      before first BM of 1.25 mg. Three patients (1.65%) experienced an adverse drug
      event leading to drug discontinuation, with 2 developing bradycardia that
      resolved with drug discontinuation alone. CONCLUSIONS: SQ neostigmine may be
      reasonable for management of ileus, ACPO, or refractory constipation, though use
      should be avoided in patients with new-onset heart block, a history of second
      degree heart block, or following bowel resection with primary anastomosis.
      Despite the low incidence of adverse drug events observed, monitoring for
      bradycardia with telemetry may be considered.

PMID- 29359575
TI  - Safety of Insulin Lispro and a Biosimilar Insulin Lispro When Administered
      Through an Insulin Pump.
AB  - BACKGROUND: SAR342434 (U100; SAR-Lis; insulin lispro) is a biosimilar/follow-on
      to insulin lispro (U100; Ly-Lis). Similar pharmacokinetics/pharmacodynamics
      between the two products has been demonstrated in a hyperinsulinemic euglycemic
      clamp study. The current study evaluated the safety of SAR-Lis and Ly-Lis when
      administered by continuous subcutaneous insulin infusion (CSII; insulin pumps).
      METHODS: This was a randomized, open-label, 2 * 4-week, two-arm crossover study
      in 27 patients with type 1 diabetes mellitus (NCT02603510). The main outcome was
      the incidence of infusion set occlusions (ISOs), defined as failure to correct
      hyperglycemia (plasma glucose >=>= 300 mg/dl) by 50 mg/dl within 60 minutes by
      insulin bolus via the pump. Secondary outcomes included intervals between
      infusion set changes, treatment-emergent adverse events (TEAEs) including
      infusion site, hypersensitivity reactions and hypoglycemic events, and safety.
      RESULTS: The number of patients reporting at least one ISO was small: 6/25
      patients on SAR-Lis reported 14 ISOs and 4/27 on Ly-Lis reported nine ISOs. The
      estimated difference in ISO risk for SAR-Lis versus Ly-Lis was 7.9% (95% CI, 
      1.90 to 17.73). Mean interval between infusion set changes for any reason was
      similar with SAR-Lis (3.09 days) and Ly-Lis (2.95 days). The event rate
      (events/patient-month) of any hypoglycemia was similar with SAR-Lis (7.15) and Ly
      Lis (7.98), as was the percentage of patients who experienced any TEAE (12.0% and
      14.8%). CONCLUSION: Both SAR-Lis and Ly-Lis were well tolerated by patients using
      insulin pumps. The results do not suggest a clinically significant difference in
      the risk of ISO between SAR-Lis and Ly-Lis when used in CSII.

PMID- 29359576
TI  - Transforming an idea into a scholarly project.
AB  - OBJECTIVES: This article describes components of a workshop designed to orientate
      psychiatric trainees to the task of conducting a scholarly project. The aims are:
      to promote an approach that incorporates principles of adult learning to guide
      trainees who are undertaking research; to allow trainees to transform their ideas
      into more tangible research questions; and to enable supervisors to reflect on
      delivering similar content in scholarly project workshops. METHODS: The workshop
      comprised: creating a safe space to explore ideas; discussing the process of
      posing a question or hypothesis; using group interactions to generate concepts;
      and considering personal values that influence the choice of research methodology
      to answer a question. RESULTS: Examples are provided from the workshop. The
      process enabled trainees to generate and distil ideas into more concrete
      questions and methods in three phases: introductory, exploratory and tangible.
      CONCLUSIONS: Adult learning principles may assist trainees to develop their ideas
      for a scholarly project into research questions that are relevant to clinical
      practice. Harnessing the creative potential of a peer collective may encourage
      deeper inquiry, shifts to a tangible output and a sustained interest in research.

PMID- 29359577
TI  - Phage therapy in allergic disorders?
AB  - Allergic disorders pose a growing challenge to medicine and our society.
      Therefore, novel approaches to prevention and therapy are needed. Recent progress
      in studies on bacterial viruses (phages) has provided new data indicating that
      they have significant immunomodulating activities. We show how those activities
      could be translated into beneficial effects in allergic disorders and present
      initial clinical data that support this hope. Impact statement Allergic disorders
      pose a growing challenge to medicine and our society, so new approaches to
      prevention and therapy are urgently needed. Our article summarizes progress that
      has been recently made and presents a shift in our understanding of the
      immunobiological significance of bacterial viruses (phages). Currently, phages
      may be considered not only as mere "bacteria eaters" but also as regulators of
      immunity. The new understanding of phages as important factors in maintenance of
      immune homeostasis opens completely new perspectives for their use in controlling
      aberrant immune responses. It is likely that this new knowledge could be
      translated into novel means of immunotherapy of allergic disorders.

PMID- 29359578
TI  - The development and implementation of a discharge checklist for psychiatric
      inpatients: a pilot study.
AB  - OBJECTIVES: Readmission rates are a routinely used measure of patient and service
      outcomes, potentially improved by discharge planning. This pilot study aimed to
      develop a discharge checklist for psychiatric inpatients, exploring its
      feasibility, applicability, and impact on readmission rates. METHODS: The study
      used a quasi-experimental, pre-post intervention design. The checklist was
      designed from an evidence-based literature review, and introduced for a three
      month period, comparing 28-day readmission rates with the previous three months
      using interrupted time series analysis. RESULTS: Checklists were completed for
      80% of patients in the trial period, with 100% completion of checklist items.
      Demographic and clinical details for pre- and post-intervention groups were
      closely aligned. There was a small, but statistically non-significant, reduction
      in readmission rates. CONCLUSIONS: There was a high rate of checklist completion.
      The lack of significant reductions in readmission rates supports more development
      of the checklist application and design before a longer implementation period and
      re-evaluation.

PMID- 29359579
TI  - Reliability and Validity of the Short Falls Efficacy Scale International in
      English, Mandarin, and Bahasa Malaysia in Malaysia.
AB  - While the prevalence of falls among Malaysian older adults is comparable to other
      older populations around the world, little is currently known about fear of
      falling in Malaysia. The Falls Efficacy Scale International (FES-I) and short FES
      I scales to measure fear of falling have not yet been validated for use within
      the Malaysian population, and are currently not available in Bahasa Malaysia
      (BM). A total of 402 participants aged >=63 years were recruited. The
      questionnaire was readministered to 149 participants, 4 to 8 weeks after the
      first administration to determine test-retest reliability. The original version
      of the 7-item short FES-I is available in English, while the Mandarin was adapted
      from the 16-item Mandarin FES-I. The BM version was translated according to
      protocol by four experts. The internal structure of the FES-I was examined by
      factor analysis. The 7-item short FES-I showed good internal reliability and test
      retest reliability for English, Mandarin, and BM versions for Malaysia.

PMID- 29359580
TI  - Subjective Age and Its Correlates Among Middle-Aged and Older Adults.
AB  - The present study evaluates discrepancies in subjective age as reported by middle
      age persons (aged 44-64 years) in comparison to older adults (aged 65 years and
      older), using a multidimensional definition of the concept. A convenience sample
      of 126 middle-aged and 126 older adults completed subjective age measures (felt
      age, desired age, and perceived old age), attitudes toward older adults,
      knowledge about aging, and sociodemographic questionnaires. Overall, participants
      reported feeling younger than they actually were and wanting to be younger than
      their chronological age. Perceived mean for old age was about 69 years.
      Discrepancies in felt age and desired age were significantly larger for the older
      group compared to the middle-aged group. Regarding perceived old age, compared to
      the younger group, older adults reported that old age begins at an older age.
      Findings suggest that middle-aged and older adults' perceptions regarding
      themselves and regarding old age in general are independent and need, therefore,
      separate research and practical attention.

PMID- 29359581
TI  - A review discussing fluciclovine (18F) PET/CT imaging in the detection of
      recurrent prostate cancer.
AB  - A significant number of patients radically treated for prostate cancer (PCa) will
      develop prostate-specific antigen recurrence (27-53%). Localizing the anatomical
      site of relapse is critical, in order to achieve the optimal treatment
      management. To date the diagnostic accuracy of standard imaging is low. Several
      desirable features have been identified for the amino-acid-based PET agent,
      fluciclovine (18F) including: long 18F half-life which allows more practical use
      in centers without a cyclotron onsite; acting as a substrate for amino acid
      transporters upregulated in PCa or associated with malignant phenotype; lacking
      of incorporation into protein; and limited urinary excretion. Fluciclovine (18F)
      is currently approved both in USA and Europe with specific indication in adult
      men with suspected recurrent PCa based on elevated prostate-specific antigen
      following prior treatment.

PMID- 29359582
TI  - Paliperidone palmitate three-month depot formulation: a helpful innovation with
      practical pitfalls.
AB  - OBJECTIVE: Paliperidone palmitate is now available as a three-month depot
      injection. This paper will review the pharmacokinetics, pharmacodynamics,
      efficacy and tolerability, as well as practical issues and pitfalls for
      clinicians with this innovative treatment for schizophrenia. CONCLUSION: The
      three-month depot formulation of paliperidone for the treatment of schizophrenia
      is not a new compound. The nanocrystalline structure of the three-month
      formulation is larger and takes longer to disperse than the one-month
      formulation, hence its extended depot action. As expected, it is non-inferior to
      one-month depot paliperidone, and superior to placebo, for the treatment of
      schizophrenia. The side effect profile of three-month paliperidone is identical
      to the one-month formulation. The relapse rate on treatment is low, and the
      median time to relapse after ceasing the drug is 395 days. An understanding of
      half-life and kinetics is crucial for clinicians using this compound, and the
      loading strategy is important to ensure effectiveness. There are significant
      challenges: ensuring timely administration and switching a three-month depot
      treatment to another antipsychotic may be problematic. Paliperidone palmitate
      three-month depot injection represents an advance for both convenience and
      effectiveness in the long term psychopharmacological treatment of schizophrenia.

PMID- 29359583
TI  - Onosmanones A and B, two novel quinonoid xanthenes from Onosma paniculatum.
AB  - Onosmanones A (1) and B (2), two novel quinonoid xanthenes with two geranyl
      groups, have been isolated from the whole plants of Onosma paniculatum. Their
      structures were elucidated on the basis of one- and two-dimensional NMR
      techniques.

PMID- 29359584
TI  - In vitro comparative cytotoxicity study of aminated polystyrene, zinc oxide and
      silver nanoparticles on a cervical cancer cell line.
AB  - Nanoparticles use in nano-biotechnology applications have increased significantly
      with Aminated polystyrene amine (AmPs NP), Zinc oxide (ZnO NP), and Silver (Ag
      NP) nanoparticles utilized in wide variety of consumer products. This has
      presented a number of concerns due to their increased exposure risks and
      associated toxicity on living systems. Changes in the structural and
      physicochemical properties of nanoparticles can lead to changes in biological
      activities. This study investigates, compares, and contrasts the potential
      toxicity of AmPs, ZnO and Ag NPs on an in vitro model (HeLa cells) and assesses
      the associated mechanism for their corresponding cytotoxicity relative to the
      surface material. It was noted that NPs exposure attributed to the reduction in
      cell viability and high-level induction of oxidative stress. All three test
      particles were noted to induce ROS to varying degrees which is irrespective of
      the attached surface group. Cell cycle analysis indicated a G2/M phase cell
      arrest, with the corresponding reduction in G0/G1 and S phase cells resulting in
      caspase-mediated apoptotic cell death. These findings suggest that all three NPs
      resulted in the decrease in cell viability, increase intracellular ROS
      production, induce cell cycle arrest at the G2/M phase and finally result in cell
      death by caspase-mediated apoptosis, which is irrespective of their differences
      in physiochemical properties and attached surface groups.

PMID- 29359585
TI  - A new coumarin and a new norlignan from Ficus tsiangii.
AB  - Chemical investigation of the stem bark of Ficus tsiangii led to the isolation of
      a new coumarin ficuscoumarin (1) and a new norlignan ficuslignan (2) by
      chromatographic methods. Their structures were elucidated on the basis of
      spectroscopic analyses.

PMID- 29359586
TI  - Change of BNP between admission and discharge after ST-elevation myocardial
      infarction (Killip I) improves risk prediction of heart failure, death, and
      recurrent myocardial infarction compared to single isolated measurement in
      addition to the GRACE score.
AB  - OBJECTIVE: In ST-elevation myocardial infarction, 7-15% of patients admitted as
      Killip I will develop symptomatic heart failure or decreased ejection fraction.
      However, available clinical scores do not predict the risk of severe outcomes
      well, such as heart failure, recurrent myocardial infarction, and sudden death in
      these Killip I individuals. Therefore, we evaluated whether one vs two
      measurements of BNP would improve prediction of adverse outcomes in addition to
      the GRACE score in ST-elevation myocardial infarction/Killip I individuals.
      METHODS: Consecutive patients with ST-elevation myocardial infarction/Killip I (
      n=167) were admitted and followed for 12 months. The GRACE score was calculated
      and plasma BNP levels were obtained in the first 12 h after symptom onset (D1)
      and at the fifth day (D5). RESULTS: Fifteen percent of patients admitted as
      Killip I developed symptomatic heart failure and/or decreased ejection fraction
      in 12 months. The risk of developing symptomatic heart failure or ejection
      fraction <40% at 30 days was increased by 8.7-fold (95% confidence interval: 1.10
      662, p=0.046) per each 100 pg/dl increase in BNP-change. Both in unadjusted and
      adjusted Cox-regressions, BNP-change as a continuous variable was associated with
      incident sudden death/myocardial infarction at 30 days (odds ratio 1.032 per each
      increase of 10 pg/dl, 95% confidence interval: 1.013-1.052, p<0.001), but BNP-D1
      was not. The GRACE score alone showed a moderate C-statistic=0.709 ( p=0.029),
      but adding BNP-change improved risk discrimination (C-statistic=0.831, p=0.001).
      Net reclassification confirmed a significant improvement in individual risk
      prediction by 33.4% (95% confidence interval: 8-61%, p=0.034). However, GRACE
      +BNP-D1 did not improve risk reclassification at 30 days compared to GRACE (
      p=0.8). At 12 months, BNP-change was strongly associated with incident sudden
      death/myocardial infarction, but not BNP-D1. CONCLUSIONS: Only BNP-change
      following myocardial infarction was associated with poorer short- and long-term
      outcomes. BNP-change also improves risk reclassification in addition to the GRACE
      score.

PMID- 29359587
TI  - Secondary use of hospital information system data for safe bedside radiography in
      terms of patient factors.
AB  - OBJECTIVE: The purpose of this study was to use patient data gathered by a
      hospital information system (HIS) to improve the safe performance of bedside
      radiography. METHOD: Hierarchical cluster analysis was used to investigate the
      factors of hospitalised patients who had undergone radiography in the X-ray room
      or at the bedside. Logistic regression analysis was then performed to quantify
      patient factors and calculate the probability of undergoing general radiography
      or bedside radiography. RESULTS: Patients were grouped into six clusters by
      hierarchical cluster analysis on the basis of their factors. We found a
      remarkable difference between clusters for the ratio of bedside radiography.
      Results indicated that "types of transportation" and "level of mobility" related
      to the ratio of bedside radiography. Logistic regression analysis of the
      associations between the probability of undergoing bedside radiography and
      patient factors indicated that type of transportation and level of mobility were
      highly correlated with bedside radiography or general radiography. CONCLUSION:
      Our results suggested that the secondary use of HIS data for the quantitative
      evaluation of patient factors and implementation of those quantitative values in
      medical records may be useful for the safe performance of bedside radiography as
      well as providing a method of decision support for doctors to order bedside
      radiography.

PMID- 29359588
TI  - Assessment of health provider readiness for telemedicine services in Uganda.
AB  - BACKGROUND: There are few telemedicine projects in Africa that have reached
      scale. One of the reasons proposed for this has been failure to assess health
      provider readiness for telemedicine prior to implementation. OBJECTIVE: To assess
      health provider readiness for implementation and integration of telemedicine
      services at three levels of Uganda's health facilities, namely, a national
      referral hospital (NRH), regional referral hospitals (RRHs) and level 4 health
      centres (HC-IVs) and to investigate factors associated with readiness for
      telemedicine. METHOD: A cross-sectional descriptive study was conducted at public
      healthcare facilities in Uganda. One RRH and HC-IV was identified from each of
      the Western, Eastern and Northern regions using a multistage random sampling
      technique. Mulago Hospital, which doubles as an RRH and HC-IV in the central
      region, was purposively identified for the study. After validation, a
      questionnaire was distributed for self-administration to senior administrators
      and doctors selected at the NRH, RRHs and HC-IVs. Data were analysed using
      bivariate associations between the outcome and the potential independent
      variables. RESULTS: In total, 114 healthcare workers completed the questionnaire.
      Of the respondents, 24 (21%) were from HC-IVs, 44 (39%) were from RRHs, and 46
      (40%) from NRH. Doctors made up 45.8% (11) of respondents at HC-IVs, 59% (26) at
      RRHs, and 30.4% (14) at NRH. Administrators across all health facility levels
      were more likely to integrate telemedicine into the healthcare system than
      doctors (odd ratio = 1.39 [95% confidence interval = 0.38-4.95]). A significant
      association existed between the state of readiness and type of health facility, p
      < 0.001. The NRH and RRHs are more likely to integrate telemedicine into their
      systems than the HC-IVs. Among the factors investigated (job title, health
      facility, technology type, reason for referral and frequency of electronic
      communication), the level of health facility and title or role of healthcare
      worker were found to have a significant statistical association with being ready
      to integrate telemedicine into the healthcare system. CONCLUSION: Health provider
      readiness to integrate telemedicine services varies at the different levels of
      the health facility and job title or role. However, referral hospitals and
      administrators were more likely to integrate telemedicine than HC-IVs and
      doctors, respectively. While this study shows physicians and administrators are
      ready, other sectors (nurses, allied healthcare workers, public) will also need
      to be assessed.

PMID- 29359589
TI  - Four new dammarane-type triterpenes derivatives from hydrolyzate of total
      Gynostemma pentaphyllum saponins and their bioactivities.
AB  - Phytochemical investigation of hydrolysate of total G. pentaphyllum saponins led
      to the isolation of four novel triterpenes, Gypensapogenin U (1), Gypensapogenin
      V (2), Gypensapogenin W (3) and Gypensapogenin X (4). The structures of these
      compounds were identified by 1D, 2D-NMR and HR-ESI-MS evidences. Additionally,
      the protective activity of these new compounds against cardiomyocytes injury
      induced by H2O2 and their cytotoxic activity against t-HSC/Cl-6 cells were
      evaluated.

PMID- 29359590
TI  - Association of carotid intima media thickness with atherogenic index of plasma,
      apo B/apo A-I ratio and paraoxonase activity in patients with non-alcoholic fatty
      liver disease.
AB  - BACKGROUND: NAFLD patients have higher risk of atherosclerosis cardiovascular
      disease (ASCVD). apo B/apoA-I ratio and atherogenic index of plasma (AIP) have
      been suggested as biomarker for ASCVD. METHODS: apo A-I, apoB, aryl esterase
      (ARE) and paraoxonase (PON) activities and carotid intima media thickness (cIMT)
      were determined in 49 NAFLD patients and 33 controls. RESULTS: Plasma levels of
      apo A-I, adiponectin, ARE and PON activities decreased in NAFLD patients, while
      apo B, AIP and apoB/apo A-I ratio level were higher in NAFLD patients compared to
      controls. Furthermore, cIMT showed a positive association with AIP, apo B/apo A-I
      ratio and AIP + (apo B/apo A-I) in NAFLD patients. Strikingly, AIP + (apo B/apo A
      I) showed a good ability to discriminating increased cIMT in NAFLD patients.
      CONCLUSIONS: The result showed that AIP and apo B/apo A-I associated with cIMT in
      NAFLD patients; however, more study are needed to prove this concept.

PMID- 29359591
TI  - Bone marrow mesenchymal stem cells suppress IL-9 in adjuvant-induced arthritis.
AB  - Interleukin-9 (IL-9) has been shown to be upregulated in rheumatoid arthritis
      (RA). The exact role of IL-9 has not yet been effectively studied. Mesenchymal
      stem cells (MSCs) have shown a promising immunomodulatory role towards repairing
      cartilage and restoring joint function. One of the key problems influencing the
      therapeutic efficacy of stem cell therapy is the poor cell survival following
      transplantation. This is attributed to oxidative and inflammatory stresses at the
      injured sites. Hesperidin (Hsd), a flavanone present in citrus fruits, has been
      studied as potential therapeutic agents that have anti-oxidant and anti
      inflammatory activities. The objective of this study is to evaluate the
      therapeutic paracrine action of bone marrow MSCs on the IL-9 level in adjuvant
      induced arthritis (AIA) and the enhancement effect of Hsd on transplanted MSCs.
      Articular tissue inflammation and cartilage damage were assessed by histological
      scoring. Antinuclear autoantibodies, tumour necrosis factor-alpha (TNF-alpha), IL
      9, IL-4, interferon gamma (IFN-delta), and transforming growth factor-beta1 (TGF
      beta1), as well as malondialdehyde (MDA), glutathione (GSH), and superoxide
      dismutase (SOD) levels, were assessed in spleen tissue homogenates after
      treatment with MSCs either alone or combined with Hsd for 4 weeks in an AIA rat
      model. Results of this study confirmed that MSCs decreased IL-9 levels in AIA and
      provide novel insights into the application of Hsd on MSC-based treatments.
      Highlights Adjuvant-induced arthritis (AIA) is one of the most widely used models
      that has a great similarity to rheumatoid arthritis (RA). Few studies in recent
      years have estimated IL-9 in rheumatic diseases and it remains an understudied
      cytokine. For the first time, bone marrow mesenchymal stem cells (MSCs) therapy
      has a vital role in splenocytes IL-9 level and further studies are required.
      Combined therapy of MSCs with antioxidants as hesperidin (Hsd) can alleviate
      oxidative stress and enhance stem cells immunomodulatory action.

PMID- 29359592
TI  - Performance and physiological analysis of 500 km non-stop cycling: a case study.
AB  - Ultra-endurance sports have gained popularity over the last years. In this case,
      a well-trained cyclist completed 503.5 km non-stop (33.3 km.h-1). Speed and power
      output were reduced during the trial, being the reduction of power attributable
      to changes in pedal velocity rather than pedal forces. Heart rate (HR) showed an
      initial cardiovascular drift and progressively decreased independently of power.
      A decreased HR variability, a marked inflammatory response, signs of muscle
      damage and alterations of the haematological profile were observed after the
      trial. These adverse physiological effects were still present 24-48 h after
      exercise. A reduction in handgrip maximal voluntary contraction was observed
      immediately after the trial and 24 h later despite these muscles being minimally
      active during exercise. These findings show the high levels of stress to which
      the organism is subjected during ultra-endurance exercise even in the case of a
      trained cyclist.

PMID- 29359593
TI  - Individuality matters for substrate-size preference in the Nile tilapia
      juveniles.
AB  - Preference tests have usually been used to identify nonhuman animal preferences
      for welfare purposes (environmental enrichment), but they are mostly at the group
      level-that is, group preferences for resources or environmental conditions.
      However, a more robust method was developed to analyze animal preference, and
      this method detected clear individual variation in preferences of Nile tilapia
      fish (Oreochromis niloticus) selecting different background colors. Here, a clear
      individual variability of preference was found for another type of enrichment-the
      sizes of substrate. Despite this variability, a consistent response was detected
      at the group level: Small gravel was less frequently preferred than avoided, and
      the more decided fish (those who preferred only one substrate size) never
      preferred gravel over sand-size substrate. That is, Nile tilapia avoided gravel
      and preferred smaller substrate, and this finding was possibly associated with
      their mouth gap. Considering that small gravel is a substrate often used for fish
      rearing, these findings highlight fish keepers' incorrect perception of fish
      needs, based mostly on arbitrary criteria instead of actual fish preferences and
      without considering individual needs.

PMID- 29359594
TI  - Methylcyclopentadienyl manganese tricarbonyl increases cell vulnerability to
      oxidative stress on rat thymocytes.
AB  - Methylcyclopentadienyl manganese tricarbonyl (MMT) is used as a gasoline
      antiknock additive. However, the toxic effect of MMT is currently not well
      understood. In this study, we investigated the toxic effect of MMT on rat
      thymocytes using a flow cytometer and fluorescent probes. MMT at 100-300 uM
      significantly increased the population of cells exhibiting propidium
      fluorescence, i.e., the population of dead cells. The intensity of BES-So-AM
      fluorescence significantly increased when using 100 uM MMT. In addition, the
      intensity of oxonol fluorescence in rat thymocytes increased with the treatment
      with MMT in a concentration-dependent manner (10-100 uM). The toxic effect of MMT
      was inhibited by quercetin, antioxidant flavonoid. Moreover, co-treatment with 30
      100 uM MMT and 100 uM H2O2 increased the cell lethality further. These results
      indicate that MMT increases cell vulnerability to oxidative stress on rat
      thymocytes. This study provides insight into the toxic effect of MMT on the
      immune system.

PMID- 29359595
TI  - Acute and developmental toxicity assessment of erincine A-enriched Hericium
      erinaceus mycelia in Sprague-Dawley rats.
AB  - This study aimed to establish an in vitro model to confirm the efficacy of
      erinacine A-enriched Hericium erinaceus (EAHE) mycelia and investigate its
      potential adverse effects in a preclinical experimental setting, including an
      assessment on the oral administration of EAHE mycelia in acute and prenatal
      developmental toxicity tests. At a single dose of 5000 mg/kg body weight, EAHE
      mycelia elicited no death or treatment-related signs of toxicity in ten Sprague
      Dawley rats of both sexes during the 14 days of the experimental period. After
      considering the recommended dose range of EAHE mycelia from the acute toxicity
      test as well as the therapeutic doses, EAHE mycelia was administered to 66
      pregnant rats in the low, medium, and high-dose groups by gavage at 875, 1750,
      and 2625 mg/kg body weight, respectively. All dams were subjected to a Caesarean
      section on the 20th day of pregnancy, and the fetuses were examined for any
      morphological abnormalities. Results indicated that weight of uterus, fetal body
      weight, number of corpora lutea, implantation sites, pre-implantation loss, and
      post-implantation loss of the treatment groups and the control group exhibited no
      statistical difference. In addition, no significant differences were observed in
      the fetal external, organ, and skeletal examinations. Taken together, it can be
      concluded that EAHE mycelia is considered safe and practically nontoxic for
      consumption within the appropriate doses and investigation period in this study.

PMID- 29359596
TI  - Treatment of AO/OTA Type C Pilon Fractures Through the Anterolateral Approach
      Combined With the Medial MIPO Technique.
AB  - BACKGROUND: The purpose of this study was to evaluate the clinical and
      radiographic results of the treatment of AO/OTA type C pilon fracture via the
      anterolateral approach using a low-profile plate combined with medial minimally
      invasive plate osteosynthesis (MIPO). METHODS: We retrospectively reviewed 28
      ankles with AO/OTA type C pilon fractures that were treated using the
      anterolateral approach combined with medial MIPO. Mean age was 46 years (range,
      19 to 75), and the mean follow-up period was 25 months (range, 14 to 50).
      Clinical results were assessed using the visual analogue scale (VAS) and the
      American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale. Range of
      motion (ROM) of the ankle joint was measured, and postoperative complications
      were investigated via chart review. RESULTS: The VAS and AOFAS Ankle-Hindfoot
      Scale were 2 and 89, respectively, at the last follow-up. Ankle ROM at the last
      follow-up was 13 degrees (range, 5 to 20) in dorsiflexion and 38 degrees (range,
      35 to 40) in plantarflexion. All the fractures united without additional surgery.
      One patient (3.6%) had a deep infection at the fibular fracture site, and 1
      patient (3.6%) had partial skin necrosis. CONCLUSION: This combined technique for
      AO/OTA type C pilon fracture resulted in good ROM of the ankle joint with
      reasonable function with a fairly low wound complication rate. However, further
      research on defined indications with a comparison group from multiple centers is
      necessary to determine if this technique is better than alternative surgical
      approaches. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29359597
TI  - Prevalence of Vitamin D Deficiency in Patients With Talar Osteochondral Lesions.
AB  - BACKGROUND: Vitamin D deficiency affects over 1 billion people worldwide and is
      common in foot and ankle patients. The prevalence in those with osteochondral
      lesions of the talus (OLTs) is unknown. This study identified the prevalence and
      risk factors for hypovitaminosis D in patients with an OLT. METHODS: Serum
      25(OH)D levels were obtained from patients presenting with an OLT from May to
      November during 2007 to 2016. Hypovitaminosis D was defined as 25(OH)D less than
      30 ng/mL (75 nmol/L). Patients presenting with an acute ankle sprain (AS) during
      the same months served as a control group. Specific medical risk factors for
      hypovitaminosis D were recorded. The final OLT population included 46 patients
      (31 women [67.4%]; mean [SD] age 43.6 [14.8] years). The comparison AS group had
      40 patients (32 women [80.0%]; mean [SD] age 56.2 [13.0] years). RESULTS: The
      mean (SD) 25(OH)D in the OLT and AS cohorts were 31.2 (12.6) ng/mL and 37.1
      (13.5) ng/mL, respectively ( P = .039). Hypovitaminosis D was identified in 54%
      of the OLT population and 28% of the AS population ( P = .012). CONCLUSION:
      Hypovitaminosis D is intimately related to decreased bone mineral density. This
      study identified a significantly higher rate of hypovitaminosis D in patients
      with an OLT compared to a cohort of AS patients. These findings suggest that when
      patients present with an OLT, health care providers should consider evaluating
      for and treating hypovitaminosis D. LEVEL OF EVIDENCE: Level III, comparative
      study.

PMID- 29359599
TI  - Is the Moderating Effect of Social Support on New Korean Mothers' Psychological
      Distress Contingent on Levels of Marital Quality?
AB  - This study examines how levels of marital quality change the effect of social
      support on postpartum psychological distress among new Korean mothers using the
      Panel Study on Korean Children (N = 1585). In accord with findings from previous
      studies, this study shows that low marital quality negatively affects new
      mothers' mental health, but that social support alleviates psychological distress
      independent of marital quality. The main finding of this research is that the
      moderating effect of social support is contingent on levels of marital quality.
      Aggregated social support moderates the effects of marital quality on new
      mothers' mental health only when the level of marital quality is low.
      Furthermore, each dimension of social support (emotional, informational, and
      instrumental) only has a moderating effect when marital quality is low. The
      findings highlight the fact that the moderating effect of social support varies
      with the individual context and so customized social support that fits individual
      needs matters for the mental health of new mothers.

PMID- 29359598
TI  - Using 3D finite element models verified the importance of callus material and
      microstructure in biomechanics restoration during bone defect repair.
AB  - BACKGROUND: There is lack of further observations on the microstructure and
      material property of callus during bone defect healing and the relationships
      between callus properties and the mechanical strength. METHODS: Femur bone defect
      model was created in rabbits and harvested CT data to reconstruct finite element
      models at 1 and 2 months. Three types of assumed finite element models were
      compared to study the callus properties, which assumed the material elastic
      property as heterogeneous (R-model), homogenous (H-model) or did not change from
      1 to 2 months (U-model). RESULTS:  The apparent elastic moduli increased at 2
      months (from 355.58 +/- 132.67 to 1139.30 +/- 967.43 MPa) in R-models. But there
      was no significant difference in apparent elastic moduli between R-models (355.58
      +/- 132.67 and 1139.30 +/- 967.43 MPa) and H-models (344.79 +/- 138.73 and
      1001.52 +/- 692.12 MPa) in 1 and 2 months. A significant difference of apparent
      elastic moduli was found between the R-model (1139.30 +/- 967.43 MPa) and U-model
      group (207.15 +/- 64.60 MPa) in 2 months. CONCLUSIONS: This study showed that the
      callus structure stability remodeled overtime to achieve a more effective
      structure, while the material quality of callus tissue is a very important factor
      for callus strength. At the meantime, this study showed an evidence that the
      material heterogeneity maybe not as important as it is in bone fracture model.

PMID- 29359600
TI  - Mental Health Indicators of Suicide in Cambodian Women.
AB  - Global suicide rates are steadily increasing, and suicide completions in Asia
      outnumber those in Western countries. Young females are especially at risk, with
      higher rates of completion and lack of suicide support because of familial and
      cultural stigma and constraints. Lack of infrastructure to systematically record
      suicide deaths and attempts makes studying suicide in low- and middle-income
      countries challenging. Given the critical public health need for suicide
      intervention and prevention, research on suicide is crucial. The present study
      adds to the lack of information regarding suicide in Cambodia by exploring
      reports of attempted suicide by women from a nationally representative sample of
      Cambodian women (N = 1813). In a series of logistic regression models, findings
      indicate that a culturally salient measure of Cambodian syndromes, symptoms of
      depression, and posttraumatic stress disorder contributed to increased odds of
      attempting to commit suicide. Implications for policymakers and interventionists
      within Cambodia and Asian contexts are discussed.

PMID- 29359601
TI  - Rising Awareness of Palliative Care in the Asia-Pacific Region.

PMID- 29359602
TI  - The Taiwan Adolescent to Adult Longitudinal Study (TAALS): Methodology and Cohort
      Description.
AB  - The objective of the study was to introduce the methodology and report on cohort
      description of Taiwan Adolescent to Adult Longitudinal Study (TAALS). TAALS is
      the first nationwide longitudinal survey among Taiwan adolescents, linked with
      the National Health Insurance Research Database (NHIRD) to obtain complete
      medical records of respondents in the future. The TAALS project employed the
      principle of probability proportional to size (PPS) sampling method. Data were
      collected by questionnaire from 18 064 school students participating in 2015
      formal survey, with good sample representation via a goodness-of-fit test after
      weighting adjustments. Through expert evaluation and statistics tests, TAALS
      shows a well nationally representation, validity, and reliability. Results
      indicate that the vocational school students had poor healthy behavior than other
      education systems, supporting the hypothesis that different learning environment
      will develop different health behaviors. TAALS can serve as a foundation for
      analyzing health trajectories of Taiwan adolescents.

PMID- 29359603
TI  - Parental Education Level and Dental Caries in School Children Living in Dili,
      Timor-Leste.
AB  - Timor-Leste struggles with problems of poverty and inequalities that underlie
      many health disparities, including oral health. This study aimed to determine the
      association between parental education and dental caries in school children aged
      6 to 17 years from 40 randomly selected schools in 4 Dili subdistricts. A
      questionnaire and oral examination collected data and multivariable log binomial
      models were used for data analysis. Results indicate no association between
      parental education level and the prevalence of untreated decay in deciduous teeth
      ( P = .96). There was an association between parental education level and
      untreated decay in permanent teeth ( P = .03) and untreated decay overall ( P =
      .01). Children whose parents had higher education levels have approximately half
      the relative risk (aRR 0.47, 95% CI 0.25-0.89) of decay compared with children
      whose parents had low levels of education.

PMID- 29359605
TI  - Facilitators and barriers in the diagnostic process of vulvovaginal complaints
      (vulvodynia) in general practice: a qualitative study.
AB  - BACKGROUND: The gap between the relatively high prevalence of provoked vulvodynia
      (PVD) in the general population and the low incidence in primary care can partly
      be explained by physicians' lack of knowledge about the assessment and management
      of PVD. OBJECTIVES: To recognize barriers and facilitators of GPs in the
      diagnostic process of women presenting with recurrent vulvovaginal complaints.
      METHODS: A qualitative focus group study in 17 Dutch GPs, five men and 12 women.
      An interview guide, based on the scientific literature and the expertise of the
      researchers, including a vignette of a patient, was used to direct the discussion
      between the GPs. The interviews were audiotaped and transcribed verbatim. A
      systematic text analysis of the transcripts was performed after data saturation
      was reached. RESULTS: Analysis of the interviews generated three major themes:
      Identifying and discussing sexual complaints, importance of gender in
      professional experience, and coping with professional uncertainty. Within these
      themes, the reluctance regarding sexual complaints, male gender, negative
      emotional responses when faced with professional uncertainty, as well as lack of
      education were barriers to the diagnostic process and management of PVD. Female
      gender and understanding that patients can profit from enquiring about sexual
      health issues were found to be facilitating factors. CONCLUSIONS: To improve the
      care for women with PVD, attitude and skills of GPs regarding taking a sexual
      history and performing a vulvovaginal examination should be addressed, as well as
      GPs' coping strategies regarding their professional uncertainty.

PMID- 29359606
TI  - Comorbidity and economic burden among moderate-to-severe psoriasis and/or
      psoriatic arthritis patients in the US Department of Defense population.
AB  - AIMS: To examine the comorbidity and economic burden among moderate-to-severe
      psoriasis (PsO) and/or psoriatic arthritis (PsA) patients in the US Department of
      Defense (DoD) population. MATERIALS AND METHODS: This retrospective cohort claims
      analysis was conducted using DoD data from November 2010 to October 2015. Adult
      patients with >=2 diagnoses of PsO and/or PsA (cases) were identified, and the
      first diagnosis date from November 2011 to October 2014 was defined as the index
      date. Patients were considered moderate-to-severe if they had >=1 non-topical
      systemic therapy or phototherapy during the 12 months pre- or 1 month post-index
      date. Patients without a PsO/PsA diagnosis during the study period (controls)
      were matched to cases on a 10:1 ratio based on age, sex, region, and index year;
      the index date was randomly selected. One-to-one propensity score matching (PSM)
      was conducted to compare study outcomes in the first year post-index date,
      including healthcare resource utilization (HRU), costs, and comorbidity
      incidence. RESULTS: A total of 7,249 cases and 72,490 controls were identified.
      The mean age was 48.1 years. After PSM, comorbidity incidence was higher among
      cases, namely dyslipidemia (18.3% vs 13.5%, p < .001), hypertension (13.8% vs
      8.7%, p < .001), and obesity (8.8% vs 6.1%, p < .001). Case patients had
      significantly higher HRU and costs, including inpatient ($2,196 vs $1,642; p <
      .0016), ambulatory ($8,804 vs 4,642; p < .001), emergency room ($432 vs $350; p <
      .001), pharmacy ($6,878 vs $1,160; p < .001), and total healthcare costs ($18,311
      vs $7,795; p < .001). LIMITATIONS: Claims data are collected for payment
      purposes; therefore, such data may have limitations for clinical research.
      CONCLUSIONS: During follow-up, DoD patients with moderate-to-severe PsO and/or
      PsA experienced significantly higher HRU, cost, and comorbidity burden.

PMID- 29359607
TI  - Benralizumab: an anti-IL-5 receptor alpha monoclonal antibody in the treatment of
      asthma.
AB  - IL-5 is a key cytokine responsible for the maturation, recruitment and survival
      of eosinophils. The role of eosinophils in pathomechanisms of severe asthma and
      association of those cells with frequent exacerbations are well accepted. Novel
      biologic agents including anti-IL-5 antibodies (mepolizumab and reslizumab) as
      well as anti-IL-5 receptor alpha chain (benralizumab) have been developed.
      Benralizumab (FasenraTM) leads to reduced eosinophil counts in airway mucosa,
      blood, sputum and a clear inhibition of eosinophil differentiation and maturation
      in the bone marrow. In clinical studies, benralizumab significantly reduces the
      rate of asthma exacerbations and has a clear oral glucocorticoid sparing effect.
      The frequency and the type of reported adverse events do not differ between
      active treatment and placebo arms.

PMID- 29359609
TI  - Rare Skin Fistulas Relating to Ascending Colonic Carcinoma: An Unusual Mode of
      Revelation.
AB  - Chronic or nonhealing wounds is a complex disease influenced by a multitude of
      factors, such as infection, ischemia, malnutrition, and diabetes and infrequently
      relates to retroperitoneal carcinoma. We present a case of an adenocarcinoma of
      ascending colon in a 68-year-old male who had lumbago and waist fistulas with
      retroperitoneal abscesses preceding other signs or symptoms of colonic
      malignancy. Supplemental information regarding the diagnosis and treatment of
      nonhealing wounds and colon carcinoma has also been included in the report.
      Adenocarcinoma of ascending colon is rarely associated with nonhealing wounds;
      nevertheless, it should be considered in cases with long-term healing
      complications. Precise diagnostic deliberation is crucial in the management and
      treatment of all chronic and long-term nonhealing lesions, and appropriately
      performed biopsies are essential to determine whether malignancy is the primary
      cause.

PMID- 29359610
TI  - Effectiveness of a bipolar vessel sealant device for ovariohysterectomy in cats
      with pyometra.
AB  - OBJECTIVES: The objective was to describe the use of a bipolar vessel sealant
      device for complete ovariohysterectomy in cats (ie, removal of both the ovarian
      pedicle and the uterine body and vessels) and to report on the feasibility of
      ovariohysterectomy in cats with pyometra. METHODS: Cats with confirmed pyometra
      and whose owners agreed to the surgical procedure were prospectively included in
      the study. Ovaries were visualised and the vessel sealant device was used to
      coagulate and cut the suspensory ligament, the ovarian pedicle and the broad
      ligament up to the level of the uterine body. Once the uterine body was measured,
      it was grasped, coagulated and transected just proximal to the cervix using the
      vessel sealant device when its diameter was <0.9 cm. Immediate postoperative and
      short-term follow-up were evaluated by clinical examination. RESULTS: Thirteen
      cases were initially included between November 2015 and February 2017. Three
      cases were subsequently excluded because of a uterine body diameter >0.9 cm. Of
      the 10 cats finally included, all were intact females, with a median age of 2.7
      years (range 0.9-9 years). Median weight was 3.7 kg (range 2.6-6.7 kg). The
      median surgery time was 10.9 mins (range 9.8-15.2 mins). Median uterus diameter
      was 0.51 cm (range 0.45-0.64 cm) and median skin incision was 4.1 cm (range 3.6
      5.1 cm). No complications during the procedures occurred in any patient. All
      cases were discharged from the hospital 1 day after surgery, without any
      abnormality. No complications were noted during the postoperative period.
      CONCLUSIONS AND RELEVANCE: The findings suggest that the bipolar vessel sealant
      device used in this study is safe in performing ovariohysterectomy for pyometra
      in cats, when the uterine body is <0.9 cm in diameter, without short-term
      complications.

PMID- 29359608
TI  - Tea polyphenols inhibit the proliferation, migration, and invasion of melanoma
      cells through the down-regulation of TLR4.
AB  - Melanoma is the most common skin cancer and malignant melanoma which can cause
      skin cancer-related deaths. Toll-like receptor 4 (TLR4) had been reported to play
      an important role in melanoma, and tea polyphenol (TP) is regarded as an
      anticancer substance. However, the relationship between TP and TLR4 in melanoma
      is not well explored. Therefore, our aim is to figure out how TP has an influence
      on melanoma. Melanoma cell lines (B16F10 and A375) were treated with TP and
      lipopolysaccharides (LPS). Western blot assay was used to examine TLR4
      expression, and MTT assay was conducted to assess proliferation. Wound healing
      assay was conducted to evaluate the migration of melanoma cells, and transwell
      assay was used to examine the melanoma cells' invasiveness. Besides, in vivo
      experiments were practiced for TP function in mice with melanoma cells. TP
      inhibited the proliferation, migration and invasion ability of melanoma cells,
      which displayed a dosage and time dependence. TLR4 was highly expressed in
      melanoma cells compared with normal skin cells. TP could suppress TLR4 expression
      both in normal melanomas and in stimulated melanomas by TLR4 agonist LPS.
      Suppressing TLR4 in melanomas could inhibit cell function (proliferation,
      migration, and invasion), and blocking the expression of 67LR could abolish TP
      function on TLR4. TP can inhibit melanoma (B16F10) growth in vivo.

PMID- 29359611
TI  - Evaluation of long-term outcome and prognostic factors of feline squamous cell
      carcinomas treated with photodynamic therapy using liposomal phosphorylated meta
      tetra(hydroxylphenyl)chlorine.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy, long-term outcome
      and prognostic factors of feline squamous cell carcinoma (SCC) treated with
      photodynamic therapy (PDT). METHODS: Cats with histologically verified SCC of the
      head and neck received an intravenous injection of liposomal phosphorylated meta
      tetra(hydroxylphenyl)chlorine (mTHPC) and 4 h later 652 nm light was delivered by
      a diode laser. One group received ?10 J/cm2, the other 20 J/cm2. Tumour response
      and duration were analysed with stage, tumour diameter, location and treatment
      intensity as prognostic factors. RESULTS: In total, 63 lesions in 38 cats
      underwent treatment with ?10 J/cm2 (n = 22) and 20 J/cm2 (n = 41). Overall
      response rate was 84% (complete remission 61%, partial remission 22%) with a mean
      progression-free interval of 35 months (median not reached) and a median overall
      survival time of 40 months (95% confidence interval 33-47). With regard to tumour
      stage, invasiveness yielded a highly significant worse outcome ( P <0.017). All
      patients with invasive tumours showed progression at less than 6 months. Larger
      lesions were associated with inferior control and treatment intensity, and tumour
      location did not influence response and duration. CONCLUSIONS AND RELEVANCE: PDT
      using a systemic photosensitiser leads to excellent long-term tumour control in
      the majority of cats. However, invasive and large tumours had a clearly inferior
      outcome, even if treated with the higher-dose intensity. This suggests that
      advanced lesions are not indications for PDT.

PMID- 29359612
TI  - A factor analytic investigation of the Mercy Evaluation of Multiple Sclerosis.
AB  - OBJECTIVE: Neurocognitive deficits commonly are an accompanying feature of
      Multiple Sclerosis (MS). A brief, yet comprehensive neuropsychological battery is
      desirable for assessing the extent of these deficits. Therefore, the present
      study examined the validity of the Mercy Evaluation of Multiple Sclerosis (MEMS)
      for use with the MS population. METHODS: Archival data from individuals diagnosed
      with MS (N = 378) by independent neurologists was examined. Cognitive domains
      assessed included processing speed and attention, learning, and memory,
      visuospatial, language, and executive functioning. A mean battery index was
      calculated to provide a general indicator of cognitive impairment within the
      current sample. RESULTS: Overall performance across participants was found to be
      in the lower limits of the average range. Results of factor analytic statistical
      procedures yielded a four-factor solution, accounting for 67% of total variance
      within the MEMS. Four neurocognitive measures exhibited the highest sensitivity
      in detecting cognitive impairment, constituting a psychometrically established
      brief cognitive screening battery, which accounted for 83% of total variance
      within the mean battery index score. CONCLUSION: Overall, the results of the
      current study suggest appropriate construct validity of the MEMS for use with
      individuals with MS, as well as provide support for previously established
      cognitive batteries.

PMID- 29359613
TI  - Eyelid arteriovenous malformation treated with pre-surgical embolization: A case
      report.
AB  - Background Arteriovenous malformations are potentially serious vascular anomalies
      that are rarely encountered in the eyelid and require a multidisciplinary
      approach. Objectives We would like to describe the technical and clinical aspects
      related to the treatment of palpebral arteriovenous malformation with selective
      embolization, followed by surgical resection. Methods A 40-year-old patient
      presented with an isolated high-flow palpebral arteriovenous malformation.
      Transarterial embolization, using a liquid embolic agent (PHILTM), was performed
      in this patient. Results Angiographic and clinical follow-up revealed good
      results with clinical regression of the mass. Conclusion Although endovascular
      treatment of palpebral arteriovenous malformations is technically challenging,
      good functional and cosmetic result was achieved. Arteriovenous malformation
      embolization using PHILTM seems to be very effective and makes subsequent
      surgical procedure safe and feasible. Level IV Evidence obtained from multiple
      time series with or without the intervention, such as case studies. Dramatic
      results in uncontrolled trials might also be regarded as this type of evidence.

PMID- 29359614
TI  - Life-threatening autoimmune warm hemolytic anemia following treatment for
      multiple sclerosis with alemtuzumab.
AB  - BACKGROUND: Alemtuzumab is a humanized monoclonal antibody directed at CD52
      approved as a disease-modifying therapy for relapsing forms of multiple sclerosis
      (MS). OBJECTIVE: To describe a case of a life-threatening autoimmune anemia
      occurring after a first course of alemtuzumab for relapsing-remitting MS in a 28
      year-old male. METHODS: Case report. RESULTS: A 28-year-old male developed a life
      threatening autoimmune anemia occurring 11 months after first alemtuzumab course.
      CONCLUSION: We report the third case of autoimmune hemolytic anemia following
      treatment with alemtuzumab in a young MS patient. Due to the severity of this
      adverse event, neurologists using this treatment should be alert.

PMID- 29359615
TI  - Correlation of Inflammatory Markers, Survival, and COX2 Expression in Oral Cancer
      and Implications for Prognosis.
AB  - Objective Peripheral blood-derived inflammation-based scores, such as the
      neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and the
      combination of platelet count and NLR, have recently been proposed as prognostic
      markers in solid tumors. The purpose of this study was to investigate the
      validity of inflammatory markers as predictive prognostic factors for locally
      advanced oral squamous cell carcinoma (OSCC). In addition, we evaluated the
      potential correlation between systemic inflammation and local expression of COX2.
      Study Design Retrospective chart review and histologic analysis. Setting Tertiary
      referral academic center. Subjects and Methods We conducted a retrospective
      analysis of 94 patients with advanced OSCC treated with surgery at our hospital
      between 2007 and 2015. The relationship among patient survival, systemic
      inflammatory markers, and local COX2 expression was evaluated. Local COX2
      expression in surgical specimens was measured by immunohistochemistry. Results
      High NLR and high PLR were associated with significantly shorter overall survival
      and cancer-specific survival. Multivariate analysis revealed that cN stage, NLR,
      and postoperative radiation/chemoradiation were significantly associated with
      overall survival and cancer-specific survival. PLR and combination of platelet
      count and NLR were significantly correlated with tumor expression of COX2.
      Finally, patients with cN2 stage disease and high local COX2 expression had a
      significantly worse prognosis than other patient groups. Conclusion Pretreatment
      inflammatory markers are useful as prognostic factors in advanced OSCC. Our study
      suggests that local COX2 may be affected by systemic inflammation and that the
      prognostic impact of COX2 expression depends on host factors and tumor
      characteristics.

PMID- 29359617
TI  - Simultaneous early-onset severe autoimmune hemolytic anemia and albuminuria
      during alemtuzumab treatment for multiple sclerosis.
AB  - BACKGROUND: Alemtuzumab, approved for multiple sclerosis (MS), can cause
      secondary autoimmune adverse events including thyroid disorders, immune
      thrombocytopenia (ITP), and glomerular nephropathies. Non-ITP autoimmune
      cytopenias are rarely reported. OBJECTIVE: To report a case of autoimmune
      hemolytic anemia (AIHA) and nephropathy in a MS patient treated with alemtuzumab.
      CASE REPORT: A 34-year-old man with MS developed albuminuria and AIHA after the
      first and only alemtuzumab treatment, with positive Coombs' direct and indirect
      tests and IgG autoantibodies. Both AIHA and nephropathy resolved 1 month after
      treatment with steroids and intravenous immunoglobulins. CONCLUSION: Our report
      adds to literature on AIHA and nephropathy after alemtuzumab treatment and
      suggests to add Coombs' tests to the screening panel required for alemtuzumab
      treatment.

PMID- 29359618
TI  - Surgical Fires in Otolaryngology: A Systematic and Narrative Review.
AB  - Objective To bring attention to the epidemiology, prevention, management, and
      consequences of surgical fires in otolaryngology by reviewing the literature.
      Data Sources PubMed, EMBASE, Web of Science, and Scopus. Review Methods
      Comprehensive search terms were developed, and searches were performed from data
      source inception through August 2016. A total of 4506 articles were identified;
      2351 duplicates were removed; and 2155 titles and abstracts were independently
      reviewed. Reference review was also performed. Eligible manuscripts described
      surgical fires involving patients undergoing otolaryngologic procedures. Results
      Seventy-two articles describing 87 otolaryngologic surgical fire cases were
      identified. These occurred during oral cavity or oropharyngeal procedures (11%),
      endoscopic laryngotracheal procedures (25%), tracheostomies (36%), "other"
      general anesthesia procedures (3%), and monitored anesthesia care or local
      procedures (24%). Oxidizing agents consisted of oxygen alone (n = 63 of 81, 78%),
      oxygen and nitric oxide (n = 17 of 81, 21%), and room air (n = 1 of 81, 1%). The
      fractional inspired oxygen delivered was >30% in 97% of surgical fires in non
      nitrous oxide general anesthesia cases (n = 35 of 36). Laser-safe tubes were used
      in only 12% of endoscopic laryngotracheal cases with endotracheal tube
      descriptions (n = 2 of 17). Eighty-six percent of patients experienced acute
      complications (n = 76 of 87), including 1 intraoperative death, and 22% of
      patients (n = 17 of 77) experienced long-term complications. Conclusion Surgical
      fires in otolaryngology persist despite aggressive multi-institutional efforts to
      curb their incidence. Guideline recommendations to minimize the concentration of
      delivered oxygen and use laser-safe tubes when indicated were not observed in
      many cases. Improved institutional fire safety practices are needed nationally
      and internationally.

PMID- 29359616
TI  - CCR2 upregulation in DRG neurons plays a crucial role in gastric hyperalgesia
      associated with diabetic gastropathy.
AB  - Background Diabetic gastropathy is a complex neuromuscular dysfunction of the
      stomach that commonly occurs in diabetes mellitus. Diabetic patients often
      present with upper gastrointestinal symptoms, such as epigastric discomfort or
      pain. The aim of this study was to assess gastric sensation in streptozocin
      induced diabetes mellitus (DM) rats and to determine the contribution of C-C
      motif chemokine receptor 2 (CCR2) signaling to gastric hyperalgesia. Results DM
      rats showed signs of neuropathy (cutaneous mechanical hyperalgesia) from two
      weeks after streptozocin administration until the end of the experiment.
      Accelerated solid gastric emptying was observed at two weeks after streptozocin
      administration compared to the controls. Intense gastric hyperalgesia also
      developed in DM rats at two weeks after streptozocin administration, which was
      significantly reduced after intrathecal administration of the CCR2 antagonist
      INCB3344. Immunochemical analysis indicated that CCR2 expression was
      substantially upregulated in small and medium-sized dorsal root ganglia neurons
      of DM rats, although the protein level of monocyte chemoattractant protein-1, the
      preferred ligand for CCR2, was not significantly different between the control
      and DM groups. Conclusions These data suggest that CCR2 activation in nociceptive
      dorsal root ganglia neurons plays a role in the pathogenesis of gastric
      hyperalgesia associated with diabetic gastropathy and that CCR2 antagonist may be
      a promising treatment for therapeutic intervention.

PMID- 29359619
TI  - Smoking cessation: Exploration of perceived technology-related information value.
AB  - This study describes a unique approach to information transfer affecting the
      perceived value of this information and related impact on smoker behavior. Data
      were collected via survey, sampling approximately 120 participants. An online
      survey tool was used for the survey creation, data collection and monitoring.
      Another online tool was used by participants to create short animation videos as
      a means of increasing their engagement with information in an experiential
      fashion. Study findings included that the process experienced by the test group
      was influential and facilitated participants' change of mind regarding enrollment
      in a smoking cessation workshop. This was partly attributable to the IKEA effect.
      The study provides evidence that a change in habits crucial to improve health and
      enhance positive lifestyle choices can be stimulated through active engagement
      with artifact creation in a technology-mediated environment.

PMID- 29359620
TI  - Adverse Event extraction from Structured Product Labels using the Event-based
      Text-mining of Health Electronic Records (ETHER)system.
AB  - Structured Product Labels follow an XML-based document markup standard approved
      by the Health Level Seven organization and adopted by the US Food and Drug
      Administration as a mechanism for exchanging medical products information. Their
      current organization makes their secondary use rather challenging. We used the
      Side Effect Resource database and DailyMed to generate a comparison dataset of
      1159 Structured Product Labels. We processed the Adverse Reaction section of
      these Structured Product Labels with the Event-based Text-mining of Health
      Electronic Records system and evaluated its ability to extract and encode Adverse
      Event terms to Medical Dictionary for Regulatory Activities Preferred Terms. A
      small sample of 100 labels was then selected for further analysis. Of the 100
      labels, Event-based Text-mining of Health Electronic Records achieved a precision
      and recall of 81 percent and 92 percent, respectively. This study demonstrated
      Event-based Text-mining of Health Electronic Record's ability to extract and
      encode Adverse Event terms from Structured Product Labels which may potentially
      support multiple pharmacoepidemiological tasks.

PMID- 29359621
TI  - Radio-scapho-capitate ligament reconstruction during proximal row carpectomy.

PMID- 29359622
TI  - The virtual hand clinic: its use in optimizing trauma footfall in a hand trauma
      unit.

PMID- 29359623
TI  - Reporting suspected adverse reactions to new commercialized medicines in real
      world.

PMID- 29359624
TI  - Blocking of matrix metalloproteinases-13 responsive peptide in poly(urethane
      urea) for potential cartilage tissue engineering applications.
AB  - The matching of scaffold degradation rate with neotissue growth is required for
      tissue engineering applications. Timely provision of proper spaces especially for
      cartilage tissue engineering plays a pivotal role in chondrocyte cluster
      formation. In this study, poly(urethane urea) was synthesized using conventional
      two-stage method by extending the isocyanate group terminated prepolymers with
      different amounts of GPLGLWARK peptide, which responses the degrading induced by
      matrix metalloproteinase 13, the main proteinase for cartilage matrix
      degradation. The Fourier transform infrared spectrometer with the attenuated
      total reflection and 1H nuclear magnetic resonance spectra revealed that the
      peptides were introduced to poly(urethane urea) according to the characteristic
      absorption bands of the peptide and the newly formed urea bonds. The ultraviolet
      visible spectroscopy spectra showed that the weight percentages of the peptide in
      the three poly(urethane urea) were 25%, 32%, and 35%. Atomic force microscopy
      images revealed that phase separation occurred in all poly(urethane urea) samples
      and became increasingly apparent with increasing amount of peptides introduced.
      Mechanical tests showed that the poly(urethane urea) strength increased with
      increasing amount of peptides in poly(urethane urea). Poly(urethane urea)
      proteolysis in matrix metalloproteinase 13 solution was more rapid than
      hydrolysis in aqueous buffer, and proteolysis rate was dependent on the amount of
      peptides in poly(urethane urea). Cell proliferation on the material surface in
      vitro displayed nontoxicity for all synthesized poly(urethane urea). In vivo
      subcutaneous implantation evaluation revealed the presence of local foreign body
      reactions triggered by poly(urethane urea) but was not due to peptide in
      poly(urethane urea). Moreover, the synthesized poly(urethane urea) with
      significant phase separation did not degrade under the matrix metalloproteinase
      13 free subcutaneous environment, but poly(urethane urea) with minimal phase
      separation was degraded by attacking of the enzymes adsorbed on the hydrophobic
      surface through non-specific adsorption.

PMID- 29359625
TI  - Vision in Alzheimer's disease: a focus on the anterior afferent pathway.
AB  - Visual dysfunction has long been recognized as a manifestation of Alzheimer's
      disease (AD), particularly in the form of visuospatial impairment during all
      stages of disease. However, investigations have revealed findings within the
      anterior (i.e., pregeniculate) afferent visual pathways that rely on retinal
      imaging and electrophysiologic methodologies for detection. Here we focus on the
      anterior afferent visual pathways in AD and the measures used for assessment,
      including optical coherence tomography, electrophysiology, color vision testing
      and threshold visual field perimetry. A brief summary of higher order visual
      dysfunction is also included to allow the reader to keep in context the broader
      findings of afferent visual dysfunction in AD.

PMID- 29359626
TI  - Cultural Self-Awareness as Awareness of Culture's Influence on the Self:
      Implications for Cultural Identification and Well-Being.
AB  - Cultural self-awareness refers to the awareness of how culture has influenced the
      self. This research investigated how such awareness might be related to cultural
      identification and well-being. In Study 1, we developed a scale measure that
      differentiated individuals' awareness of how culture has influenced them
      (cultural self-awareness) and how their own personality and personal experiences
      have influenced them (personal self-awareness). Factor analysis and item analysis
      showed a two-factor model with acceptable scale reliability. Study 2 showed that
      cultural self-awareness positively predicted well-being through higher cultural
      identification, whereas personal self-awareness positively predicted well-being
      through higher behavioral authenticity. Study 3 manipulated the valence of
      individuals' cultural experience. The indirect effect of cultural self-awareness
      on well-being was stronger when cultural experience was positive (vs. negative).
      Study 4 provided a specific cultural context for the well-being measures and
      replicated the findings of Studies 2 and 3. Implications on the link between
      culture and self were discussed.

PMID- 29359627
TI  - Advice Giving: A Subtle Pathway to Power.
AB  - We propose that interpersonal behaviors can activate feelings of power, and we
      examine this idea in the context of advice giving. Specifically, we show (a) that
      advice giving is an interpersonal behavior that enhances individuals' sense of
      power and (b) that those who seek power are motivated to engage in advice giving.
      Four studies, including two experiments ( N = 290, N = 188), an organization
      based field study ( N = 94), and a negotiation simulation ( N = 124), demonstrate
      that giving advice enhances the adviser's sense of power because it gives the
      adviser perceived influence over others' actions. Two of our studies further
      demonstrate that people with a high tendency to seek power are more likely to
      give advice than those with a low tendency. This research establishes advice
      giving as a subtle route to a sense of power, shows that the desire to feel
      powerful motivates advice giving, and highlights the dynamic interplay between
      power and advice.

PMID- 29359628
TI  - Perceiving Relationship Success Through a Motivational Lens: A Regulatory Focus
      Perspective.
AB  - The current research examined the hypothesis that the relative importance of
      growth- and security-related relationship qualities in establishing successful
      relationships depends on the motivational orientation-regulatory focus (Higgins,
      1997)-of the individual. Across four studies, we found that individuals in a
      promotion focus, whether chronic (Studies 1-2, 4) or temporarily induced (Study
      2), prioritized the presence of relationship growth versus security in perceiving
      relationship success (Studies 1-2), rated their own relationship well-being
      higher when growth (but not security) qualities were present (Study 3), and
      experienced heightened relationship well-being when room for growth was
      manipulated to appear abundant versus limited (Study 4). In contrast, prevention
      focused individuals did not place as much emphasis on growth relative to security
      (Studies 1 and 3) and, when forced to choose, preferred a relationship
      characterized by security versus growth (Study 2). These findings suggest the
      value of considering motivational orientations in understanding how relationship
      success is experienced.

PMID- 29359629
TI  - It Could Have Been True: How Counterfactual Thoughts Reduce Condemnation of
      Falsehoods and Increase Political Polarization.
AB  - This research demonstrates how counterfactual thoughts can lead people to excuse
      others for telling falsehoods. When a falsehood aligned with participants'
      political preferences, reflecting on how it could have been true led them to
      judge it as less unethical to tell, which in turn led them to judge a politician
      who told it as having a more moral character and deserving less punishment. When
      a falsehood did not align with political preferences, this effect was
      significantly smaller and less reliable, in part because people doubted the
      plausibility of the relevant counterfactual thoughts. These results emerged
      independently in three studies (two preregistered; total N = 2,783) and in meta-
      and Bayesian analyses, regardless of whether participants considered the same
      counterfactuals or generated their own. The results reveal how counterfactual
      thoughts can amplify partisan differences in judgments of alleged dishonesty. I
      discuss implications for theories of counterfactual thinking and motivated moral
      reasoning.

PMID- 29359630
TI  - Increasing Full Child Immunization Rates by Government Using an Innovative
      Computerized Immunization Due List in Rural India.
AB  - Increasing child vaccination coverage to 85% or more in rural India from the
      current level of 50% holds great promise for reducing infant and child mortality
      and improving health of children. We have tested a novel strategy called Rural
      Effective Affordable Comprehensive Health Care (REACH) in a rural population of
      more than 300 000 in Rajasthan and succeeded in achieving full immunization
      coverage of 88.7% among children aged 12 to 23 months in a short span of less
      than 2 years. The REACH strategy was first developed and successfully implemented
      in a demonstration project by SHARE INDIA in Medchal region of Andhra Pradesh,
      and was then replicated in Rajgarh block of Rajasthan in cooperation with Bhoruka
      Charitable Trust (private partners of Integrated Child Development Services and
      National Rural Health Mission health workers in Rajgarh). The success of the
      REACH strategy in both Andhra Pradesh and Rajasthan suggests that it could be
      successfully adopted as a model to enhance vaccination coverage dramatically in
      other areas of rural India.

PMID- 29359631
TI  - "We Take Care of People; What Happens to Us Afterwards?": Home Health Aides and
      Bereavement Care in Hospice.
AB  - After a hospice patient dies, hospice providers can experience a variety of
      emotional responses. While work has been done on social workers' and nurses'
      reactions to patient death, home health aides (HHAs) have been overlooked. To
      address this gap, we conducted focus groups and individual qualitative interviews
      with 14 hospice HHAs. Questions covered HHAs' grief responses and how they coped
      with grief. We found a high burden of grief reactions; many HHAs often developed
      very close patient relationships. HHAs also noted that they often started working
      with new patients almost immediately after a death, leaving little time to
      process the loss. However, HHAs found support from other HHAs, their supervisors,
      as well as family, friends, and spiritual practices to be helpful in coping with
      their grief. Future work should enhance support to HHAs around patient loss; for
      example, grief support may be embedded into hospice team activities.

PMID- 29359632
TI  - The efficacy of VIPP-V parenting training for parents of young children with a
      visual or visual-and-intellectual disability: a randomized controlled trial.
AB  - Video-feedback Intervention to promote positive parenting-visual (VIPP-V) or
      visual-and-intellectual disability is an attachment-based intervention aimed at
      enhancing sensitive parenting and promoting positive parent-child relationships.
      A randomized controlled trial was conducted to assess the efficacy of VIPP-V for
      parents of children aged 1-5 with visual or visual-and-intellectual disabilities.
      A total of 37 dyads received only care-as-usual (CAU) and 40 received VIPP-V
      besides CAU. The parents receiving VIPP-V did not show increased parental
      sensitivity or parent-child interaction quality, however, their parenting self
      efficacy increased. Moreover, the increase in parental self-efficacy predicted
      the increase in parent-child interaction. In conclusion, VIPP-V does not appear
      to directly improve the quality of contact between parent and child, but does
      contribute to the self-efficacy of parents to support and to comfort their child.
      Moreover, as parents experience their parenting as more positive, this may
      eventually lead to higher sensitive responsiveness and more positive parent-child
      interactions.

PMID- 29359633
TI  - Assessing disorganized attachment representations: a systematic psychometric
      review and meta-analysis of the Manchester Child Attachment Story Task.
AB  - Narrative story stem measures are increasingly popular for the assessment of
      attachment representations among early school-age children. Given their clinical
      and theoretical importance, disorganized representations are typically a focus of
      assessment procedures. The Manchester Child Attachment Story Task (MCAST) is one
      such measure. A systematic literature review and meta-analysis was conducted to
      evaluate the documented reliability and validity of the MCAST with a focus on
      assessing disorganized representations. Twenty-five studies were included in the
      review encompassing 1,876 children from nine countries. Results suggest that
      inter-rater reliability for the MCAST is acceptable and the prevalence of
      disorganization identified on the MCAST among various subgroups (e.g. community,
      clinical, adopted/maltreated) is comparable to prevalence estimates from other
      developmental periods using other assessment methods. In addition, prevalence of
      disorganization on the MCAST differed in hypothesized ways between the various
      subgroups. However, MCAST disorganization did not correlate in predictable ways
      with many constructs when relationships were examined within samples. Few studies
      examined the relationship of disorganization on the MCAST with parenting
      variables, aspects of adoption and maltreatment, and emotion regulation skills.
      Recommendations for further study of the MCAST and for how the tool might be
      integrated into clinical and developmental research are provided.

PMID- 29359634
TI  - Ebola and healthcare worker stigma.
AB  - AIMS: Exposure to infection is a risk for all healthcare workers. This risk
      acquires another dimension in an outbreak of highly contagious, lethal disease,
      such as the Ebola epidemic in West Africa in 2014. Healthcare workers are usually
      well and correctly informed about the risks from such diseases, but family,
      neighbours, friends, or colleagues may react strongly to the risk that staff
      might bring infection home from an epidemic overseas. Research around such
      stigmatization is scarce. We wanted to investigate how common it is, which
      expressions it assumes and how it is influenced by dissemination of information.
      METHODS: We interviewed a sample of Swedish healthcare workers who had worked in
      West Africa during the 2014 outbreak of Ebola, as well as one close contact for
      each of them, about reactions before leaving and after returning, and also about
      information received. RESULTS AND CONCLUSIONS: The majority of contact persons
      reported no or little concern, neither when the healthcare worker revealed the
      plan to leave, nor on the healthcare worker's return. The prevailing reason was
      trust in the judgement of 'their' healthcare worker, mainly using information
      received from the healthcare worker to assess risks, and relying little on other
      information channels. This means that the person assessing the risk was at the
      same time the hazard. There were indications that instructions regarding
      quarantine and self-isolation were less stringently followed by healthcare
      workers than by other aid workers in the outbreak, which could give confusing
      signals to the public. Simple, clear and non-negotiable rules should be preferred
      - also from an information perspective.

PMID- 29359635
TI  - Early detection of lung cancer potential among Egyptian wood workers.
AB  - Wood dust is known to be a human carcinogen, with a considerable risk of lung
      cancer. The increased cancer risk is likely induced through its genotoxic effects
      resulting from oxidative DNA damage. This study aimed at assessing the
      genotoxicity of wood dust and demonstrating the role of sputum PCR as a screening
      tool for early prediction of lung cancer among wood workers. The study was
      carried out in the carpentry section of a modernized factory involved with the
      manufacture of wooden furniture in Greater Cairo, Egypt. Environmental assessment
      of respirable wood dust concentrations was done. Frequency of chromosomal
      aberrations (CA%) and sister chromatid exchanges (SCE%) in peripheral blood
      lymphocytes (PBL) was assessed and comet assays were performed in samples from
      among the study population (n = 86). Levels of superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) enzymes were measured. The polymerase chain reaction
      (PCR) was used to study hypermethylation of p16 and or O6-methylguanine-DNA
      methyltransferase (MGMT) gene promoters in sputum DNA. The concentrations of
      respirable wood dust exceeded the Egyptian and international permissible limits
      with highest levels generated by sawing operations. Laboratory investigations
      revealed statistically significantly higher frequencies of CA and SCE as well as
      increased comet tail length associated with significant decrement in the levels
      of SOD and GPx among exposed group. A statistically significant elevation in the
      extent of hypermethylation was detected for the p16 and MGMT gene promoters in
      the sputum DNA of studied wood workers. The study results support the conclusion
      that prolonged unprotected occupational exposure to wood dust is associated with
      possible genotoxicity and oxidative stress that might raise the risk for
      carcinogenesis including lung cancer.

PMID- 29359637
TI  - Science to the people: A 32-nation survey.
AB  - In this article, we analyze Special Eurobarometer (2010) data via multilevel
      regression modeling and answer two questions: (a) How a country's democratization
      level is related to the rate of public engagement with science and (b) who are
      those citizens who participate in science policy-shaping and express their
      approval for democratic governance of science? Reflexive modernization and
      institutional alienation perspectives are used to examine those issues. It has
      been shown that more democratic societies on average have higher rates of public
      participation in science and support for democratic control of it. Moreover,
      those well educated and knowledgeable in the topic of science are more likely to
      engage with science, which supports the reflexive modernization perspective.
      However, distrust in scientists being considered as an indicator of institutional
      alienation from science is also crucial in both predicting actual engagement and
      support for public control over it.

PMID- 29359636
TI  - Neuropsychological state of the population living in the Aral Sea region (zone of
      ecological crisis).
AB  - Background The Aral Sea crisis has led to harmful effects on human habitat. In
      recent years, mild cognitive impairment is a growing problem. Objectives This
      article provides the results of studying the neuropsychological state of
      residents living in the crisis zone of the Aral Sea region in the case of Shalkar
      city. We have provided an assessment of the neuropsychological state of examined
      population and determined the leading pathology in this region. Methods The
      survey sample included 344 persons of reproductive age from 21 to 45 years. We
      have obtained results in biochemical studies, indicating perturbations of
      proteometabolism and lipid metabolism. Results A correlation analysis showed
      dependence between a decrease of albumin and high-density lipoproteins, an
      increase of low-density lipoproteins and parameters of cognitive function.
      Conclusions The research suggests a high prevalence of cerebrovascular pathology
      among the population, changes in cognitive function parameters, long-term and
      short-term memory problems and high levels of depression.

PMID- 29359638
TI  - Determinants of hand dermatitis, urticaria and loss of skin barrier function in
      professional cleaners in New Zealand.
AB  - This study assessed the risk of dermatitis, urticaria and loss of skin barrier
      function in 425 cleaners and 281 reference workers (retail workers and bus
      drivers). Symptoms, atopy and skin barrier function were assessed by
      questionnaire, skin prick tests, and measurement of transepidermal water loss.
      Cleaners had an increased risk of current (past 3 months) hand/arm dermatitis
      (14.8% vs. 10.0%; OR = 1.9, p < 0.05) and urticaria (11% vs. 5.3%; OR = 2.4, p <
      0.05) and were more likely to have dermatitis as adults (17.6% vs. 11.4%; OR =
      1.8, p < 0.05). The risk of atopy was not increased, but associations with
      symptoms were more pronounced in atopics. Transepidermal water loss was
      significantly higher in cleaners. Wet-work was a significant risk factor for
      dermatitis and hand washing and drying significantly reduced the risk of
      urticaria. In conclusion, cleaners have an increased risk of hand/arm dermatitis,
      urticaria and loss of skin barrier function.

PMID- 29359640
TI  - One wouldn't expect an expert bowler to hit only two pins: Hierarchical
      predictive processing of agent-caused events.
AB  - Evidence is accumulating that our brains process incoming information using top
      down predictions. If lower level representations are correctly predicted by
      higher level representations, this enhances processing. However, if they are
      incorrectly predicted, additional processing is required at higher levels to
      "explain away" prediction errors. Here, we explored the potential nature of the
      models generating such predictions. More specifically, we investigated whether a
      predictive processing model with a hierarchical structure and causal relations
      between its levels is able to account for the processing of agent-caused events.
      In Experiment 1, participants watched animated movies of "experienced" and
      "novice" bowlers. The results are in line with the idea that prediction errors at
      a lower level of the hierarchy (i.e., the outcome of how many pins fell down)
      slow down reporting of information at a higher level (i.e., which agent was
      throwing the ball). Experiments 2 and 3 suggest that this effect is specific to
      situations in which the predictor is causally related to the outcome. Overall,
      the study supports the idea that a hierarchical predictive processing model can
      account for the processing of observed action outcomes and that the predictions
      involved are specific to cases where action outcomes can be predicted based on
      causal knowledge.

PMID- 29359641
TI  - Representation of numerical magnitude in math-anxious individuals.
AB  - Larger distance effects in high math-anxious individuals (HMA) performing
      comparison tasks have previously been interpreted as indicating less precise
      magnitude representation in this population. A recent study by Dietrich, Huber,
      Moeller, and Klein limited the effects of math anxiety to symbolic comparison, in
      which they found larger distance effects for HMA, despite equivalent size
      effects. However, the question of whether distance effects in symbolic comparison
      reflect the properties of the magnitude representation or decisional processes is
      currently under debate. This study was designed to further explore the relation
      between math anxiety and magnitude representation through three different tasks.
      HMA and low math-anxious individuals (LMA) performed a non-symbolic comparison,
      in which no group differences were found. Furthermore, we did not replicate
      previous findings in an Arabic digit comparison, in which HMA individuals showed
      equivalent distance effects to their LMA peers. Lastly, there were no group
      differences in a counting Stroop task. Altogether, an explanation of math anxiety
      differences in terms of less precise magnitude representation is not supported.

PMID- 29359639
TI  - Free operant observing in humans: a translational approach to compulsive
      certainty seeking.
AB  - Excessive checking is reported in non-clinical populations and is a pervasive
      symptom in obsessive compulsive disorder (OCD). We implemented a free-operant
      task in humans, previously used in rats, wherein participants can "check" to
      reduce uncertainty. Participants can press an observing key to ascertain which of
      two main keys will, if pressed, currently lead to rewards. Over a series of
      experiments, we found that punishment robustly increased observing in non
      clinical participants and that observing persisted long after punishment was
      removed. Moreover, participants appeared insensitive to the initial costs of
      checking, and a threefold increase in the effort required to observe served to
      deter participants only to a limited degree. We also assessed observing in OCD
      patients with no known comorbidities. The patients observed more than control
      participants and were abnormally insensitive to the introduction of punishment.
      These findings support the translational value of the task, with similar
      behaviours in humans and rodents. This paradigm may serve as a unifying platform,
      promoting interaction between different approaches to analyse adaptive and
      maladaptive certainty seeking behaviours. Specifically, we demonstrate how
      seemingly disparate theoretical and empirical approaches can be reconciled
      synergistically to promote a combined behavioural and cognitive account of
      certainty seeking.

PMID- 29359642
TI  - Editorial.

PMID- 29359643
TI  - Impaired thiol-disulphide homeostasis in patients with axonal polyneuropathy.
AB  - OBJECTIVE: The objective of this study is to examine thiol-disulphide homeostasis
      in patients with polyneuropathy dominated by diabetic or non-diabetic axonal
      degeneration. MATERIALS-METHODS: Fifty-four patients diagnosed with
      polyneuropathy dominated by axonal damage and 41 healthy subjects were included
      in the study. The patients were grouped into two groups according to whether or
      not they had diabetes. The native thiol and total thiol concentrations were
      measured with the newly developed automated method. RESULTS: While there was no
      significant difference between the patients with diabetic and non-diabetic
      polyneuropathy in terms of native thiol and total thiol levels (p > 0.05), the
      native thiol and total thiol levels of the groups with both diabetic
      polyneuropathy and non-diabetic polyneuropathy were significantly low compared to
      the control group (p < 0.01). The level of disulphides in the patients with
      diabetic polyneuropathy was significantly higher than that of the patients with
      non-diabetic polyneuropathy and the healthy individuals (p < 0.05). The loss in
      the sural nerve sensory neural action potential amplitude was positively
      correlated with the decrease in the levels of both native thiol and total thiol
      (p < 0.05). DISCUSSION: In our study, we observed that the thiol-disulphide
      balance was also impaired in patients with non-diabetic polyneuropathy similar to
      patients with diabetic polyneuropathy, and we therefore considered that impaired
      the thiol-disulphide homeostasis could be the last common path in patients with
      polyneuropathy with axonal damage, regardless of the aetiology. Therefore,
      fortification of thiol deficiency with N-acetyl cysteine or alpha-lipoic acid can
      fix the thiol-disulphide balance and help decelerate the axonal damage.

PMID- 29359644
TI  - Osseous changes of the mandibular condyle affect backward-rotation of the
      mandibular ramus in Angle Class II orthodontic patients with idiopathic condylar
      resorption of the temporomandibular joint.
AB  - OBJECTIVE: To evaluate whether osseous changes of the temporomandibular joint
      (TMJ) condyle affect backward rotation of the mandibular ramus in Angle Class II
      orthodontic patients with idiopathic condylar resorption (ICR). METHODS: Twenty
      Japanese women with Class II malocclusion with ICR (ICR group) and 24 women with
      Class II malocclusion without ICR (non-ICR group) were examined. Pre-treatment
      panoramic radiographs were used to measure condylar ratios. Pre-treatment lateral
      cephalograms were used to evaluate maxillofacial morphology. RESULTS: The ICR
      group had a significantly smaller condylar ratio, greater backward rotation of
      the ramus, less labially inclined upper incisors, and a steeper occlusal plane.
      The increased backward rotation of the ramus in the ICR group was significantly
      associated with a smaller condylar ratio. CONCLUSION: Angle Class II patients
      with ICR had shorter condylar height attributable to osseous changes of the TMJ
      condyle, and the shorter condylar height may affect subsequent backward rotation
      of the ramus.

PMID- 29359645
TI  - Chronic Hepatitis C Screening, Evaluation, and Treatment Update in the Age of
      Direct-Acting Antivirals.
AB  - Globally, hepatitis C virus (HCV), the cause of one of the most common infectious
      diseases, infects approximately 4 million to 5 million Americans with
      approximately half of infected individuals undiagnosed. Some workplaces screen
      employees for HCV exposure and other bloodborne pathogens (BBP) after needlestick
      injuries, but it is not well known whether employers screen employees for HCV
      without an occupational exposure. New guidelines from the Centers for Disease
      Control and Prevention (CDC) recommend that all individuals born between 1945 and
      1965 should be screened for HCV regardless of risk; this provides an opportunity
      at the worksite for HCV outreach to employees, dependents, and retirees. To
      understand this recommendation, the management of HCV in the age of direct-acting
      antivirals (DAAs) should be reviewed. Now that new DAA treatment can cure HCV,
      occupational health nurses should identify potential HCV-positive individuals at
      the worksite via HCV education, screening, testing, and, if positive, linking to
      specialists for treatment.

PMID- 29359646
TI  - The role of coach-athlete relationship quality in team sport athletes'
      psychophysiological exhaustion: implications for physical and cognitive
      performance.
AB  - The present study aimed to examine associations between the quality of the coach
      athlete relationship and athlete exhaustion by assessing physiological and
      cognitive consequences. Male and female athletes (N = 82) representing seven
      teams across four different sports, participated in a quasi-experimental study
      measuring physical performance on a 5-meter multiple shuttle test, followed by a
      Stroop test to assess cognitive performance. Participants provided saliva samples
      measuring cortisol as a biomarker of acute stress response and completed
      questionnaires measuring exhaustion, and coach-athlete relationship quality.
      Structural equation modelling revealed a positive relationship between the
      quality of the coach-athlete relationship and Stroop performance, and negative
      relationships between the quality of the coach-athlete relationship and cortisol
      responses to high-intensity exercise, cognitive testing, and exhaustion. The
      study supports previous research on socio-cognitive correlates of athlete
      exhaustion by highlighting associations with the quality of the coach-athlete
      relationship.

PMID- 29359647
TI  - Palm-Based Neopentyl Glycol Diester: A Potential Green Insulating Oil.
AB  - BACKGROUND: The transesterification of high oleic palm oil methyl ester (HOPME)
      with neopentyl glycol (NPG) has been investigated. The present study revealed the
      application of low-pressure technology as a new synthesis method to produce NPG
      diesters. Single variable optimization and response surface methodology (RSM)
      were implemented to optimize the experimental conditions to achieve the maximum
      composition (wt%) of NPG diesters. OBJECTIVE: The main objective of this study
      was to optimize the production of NPG diesters and to characterize the optimized
      esters with typical chemical, physical and electrical properties to study its
      potential as insulating oil. METHODS: The transesterification reaction between
      HOPME and NPG was conducted in a 1L three-neck flask reactor at specified
      temperature, pressure, molar ratio and catalyst concentration. For the
      optimization, four factors have been studied and the diester product was
      characterized by using gas chromatography (GC) analysis. The synthesized esters
      were then characterized with typical properties of transformer oil such as flash
      point, pour point, viscosity and breakdown voltage and were compared with mineral
      insulating oil and commercial NPG dioleate. For formulation, different samples of
      NPG diesters with different concentration of pour point depressant were prepared
      and each sample was tested for its pour point measurement. RESULTS: The optimum
      conditions inferred from the analyses were: molar ratio of HOPME to NPG of 2:1.3,
      temperature = 182 degrees C, pressure = 0.6 mbar and catalyst concentration of
      1.2%. The synthesized NPG diesters showed very important improvement in fire
      safety compared to mineral oil with flash point of 300 degrees C and 155 degrees
      C, respectively. NPG diesters also exhibit a relatively good viscosity of 21 cSt.
      The most striking observation to emerge from the data comparison with NPG diester
      was the breakdown voltage, which was higher than mineral oil and definitely in
      conformance to the IEC 61099 limit at 67.5 kV. The formulation of synthesized NPD
      diesters with VISCOPLEX(r) pour point depressant has successfully increased the
      pour point of NPG diester from -14 degrees C to -48 degrees C. CONCLUSION: The
      reaction time for the transesterification of HOPME with NPG to produce NPG
      diester was successfully reduced to 1 hour from the 14 hours required in the
      earlier synthesis method. The main highlight of this study was the excess
      reactant which is no longer methyl ester but the alcohol (NPG). The optimum
      reaction conditions for the synthesis were molar ratio of 2:1.13 for NPG:HOPME,
      182 degrees C, 0.6 mbar and catalyst concentration of 1.2 wt%. The maximum NPG
      diester yield of 87 wt% was consistent with the predicted yield of 87.7 wt%
      obtained from RSM. The synthesized diester exhibited better insulating properties
      than the commercial products especially with regards to the breakdown voltage,
      flash point and moisture content.

PMID- 29359648
TI  - Ligand Induced Folding of the First Identified CBM69 Starch Binding Domain AmyP
      SBD.
AB  - AmyP is an alpha-amylase which shows preferential degradation to soluble starch.
      In this substrate preference its Starch Binding Domain (SBD), which was recently
      assigned to a new Carbohydrate Binding Module (CBM) family 69, plays an important
      role. In the present study, the SBD of AmyP (AmyP-SBD) was recombinantly
      expressed, purified, and structurally characterized. Using Circular Dichroism
      (CD), intrinsic fluorescence, and nuclear magnetic resonance (NMR) spectroscopy,
      the structures of AmyP-SBD in the absence and presence of substrate analogue beta
      cyclodextrin were measured. The results intriguingly showed that free form AmyP
      SBD is partially unfolded, like a compact molten globule, and could be induced by
      the ligand to fold into a relatively rigid state. Further structure determination
      for folded AmyP-SBD revealed a topology distinctive from those of SBDs from other
      CBM families. Our data indicate AmyP-SBD is a structurally novel SBD, and this
      may be helpful for understanding the properties of AmyP-SBD and CBM69 and
      elucidation of functioning mechanism of AmyP.

PMID- 29359649
TI  - Laccases, Manganese Peroxidases and Xylanases Used for the Bio-bleaching of Paper
      Pulp: An Environmental Friendly Approach.
AB  - BACKGROUND: The paper and pulp industry is a capital and resource-intensive
      industry that contributes to ecosystem toxicity and affects human beings.
      OBJECTIVE: The study aimed to appraise the potential of xylanases, laccases and
      manganese peroxidase for the bio-bleaching of paper pulp and to highlight the
      role of these enzymes as a promising substitute for chlorine-based chemical
      methods in the bleaching process. METHODS: The ligninolytic enzymes including
      xylanase, laccase and manganese peroxidase isolated from white rot fungi were
      used for pre-bleaching and bleaching of oven-dried wheat straw pulp. RESULTS:
      During the sequential enzymatic treatment of oven-dried pulp the brightness was
      improved and kappa number was reduced by 3.1% and 3.1 points respectively after
      xylanase treatment, 0.3% and 0.4 points after laccase treatment and 3% and 0.2
      points after MnP treatment. During separate treatment of pulp samples with
      individual enzymes, brightness and kappa number improved by 8% and 3 points
      respectively after xylanase treatment, by 5% and 1.7 points after laccase
      treatment and 5% and 1.8 points after treatment with MnP. During subsequent
      treatment with 4% sodium hypochlorite, the brightness was further improved by
      27.9 % for xylanase treated pulp and 29% for the laccase and MnP treated pulp.
      The xylanase was found most efficient in comparison to laccase and MnP in
      reduction of kappa number and improvement of brightness. CONCLUSION: These
      results clearly indicate the role of laccase, MnP and xylanase from white rot
      fungi as effective bio-bleaching agents. Therefore, these enzymes can facilitate
      the bleaching process without threat to environment.

PMID- 29359650
TI  - Omics Technologies for Microalgae-based Fuels and Chemicals: Challenges and
      Opportunities.
AB  - BACKGROUND: Microalgae have been suggested as promising feedstocks of significant
      biotechnological interest due to their enormous potential for the sustainable
      production of industrially valuable compounds such as lipids/fatty acids,
      proteins, metabolites, pigments, and biofuels. However, exploitation of algal
      biomass for commercial purposes is still in its infancy due to the dearth of the
      knowledge regarding state-of-the-art sophisticated technologies. OBJECTIVES: The
      main objective of the study was to review the explosions of innovative strategies
      that biological sciences have witnessed over the past several years, enabling the
      scientific community and research-based organizations to scrutinize entire
      classes of biomolecules from a cell type or whole organism, collectively titled
      as 'Omics, including genomics, transcriptomics, proteomics and lipidomics.
      METHODS: An effort has been made to analyze the relative advantages and drawbacks
      of these technologies by reviewing and consulting the available literature.
      RESULTS: Nevertheless, these 'Omics strategies have played a key role in the
      better understanding of the underlying mechanisms of specific gene products,
      regulatory constraints, metabolic pathways and potential genes and protein
      targets which might be employed in tailoring microalgae for enhanced
      productivity. In this critical review, an understanding of recent omics
      technologies, their potential applications, and limitations for microalgae-based
      fuel and other commodity chemicals are comprehensively discussed. CONCLUSION: In
      the scenario of uncertain petro-based reserves, global warming and energy
      insecurity, the exploration of metabolic potentialities of microalgae using
      "Omics" are believed to be a green and environmentally-responsive approach that
      will further expand its industrial and environmental scope.

PMID- 29359651
TI  - Thermodynamics and Kinetics Parameters of Eichhornia crassipes Biomass for
      Bioenergy.
AB  - BACKGROUND: Eichhornia crassipes is an aquatic plant well known for its role in
      soil reclamation due to the containment of valuable nutrients. Moreover, its
      biomass is an abundant and low-cost biological resource. Pyrolysis of a biomass
      offers one of the cleanest methods to harness the bioenergy stored in the
      biomass. OBJECTIVE: The present study was focused on evaluating the bioenergy
      potential of Eichhornia crassipes via pyrolysis. METHODS: Biomass of E. crassipes
      was collected from a municipal wastewater pond. Oven dried powdered biomass of E.
      crassipes was subjected to pyrolysis at three heating rates including 10, 30 and
      50  degrees C min-1 in a simultaneous Thermogravimetry-Differential Scanning
      Calorimetry analyzer under an inert environment containing nitrogen. Data
      obtained were subjected to isoconversional models of Kissenger-Akahira-Sunose
      (KSA) and Flynn-Wall-Ozawa (FWO) to understand the reaction chemistry. RESULTS:
      Kinetic parameters have shown that the pyrolysis followed first-order reaction
      kinetics. The average values of activation energies (129.71-133.03 kJ mol-1) and
      thermodynamic parameters including high heating values (18.12 MJ kg-1), Gibb's
      free energies (171-180 kJ mol-1) and enthalpy of reaction (124-127 kJ mol-1) have
      shown the remarkable bioenergy potential of this biomass. CONCLUSION: This low
      cost biomass may be used to produce liquids, gases, and biochar in a
      costefficient and environmentally friendly way via pyrolysis or co-pyrolysis in
      the future.

PMID- 29359652
TI  - Engineering Ligninolytic Consortium for Bioconversion of Lignocelluloses to
      Ethanol and Chemicals.
AB  - BACKGROUND: Rising environmental concerns and recent global scenario of cleaner
      production and consumption are leading to the design of green industrial
      processes to produce alternative fuels and chemicals. Although bioethanol is one
      of the most promising and eco-friendly alternatives to fossil fuels yet its
      production from food and feed has received much negative criticism. OBJECTIVE:
      The main objective of this study was to present the noteworthy potentialities of
      lignocellulosic biomass as an enormous and renewable biological resource. The
      particular focus was also given on engineering ligninolytic consortium for
      bioconversion of lignocelluloses to ethanol and chemicals on sustainable and
      environmentally basis. METHODS: Herein, an effort has been made to extensively
      review, analyze and compile salient information related to the topic of interest.
      Several authentic bibliographic databases including PubMed, Scopus, Elsevier,
      Springer, Bentham Science and other scientific databases were searched with
      utmost care, and inclusion/ exclusion criterion was adopted to appraise the
      quality of retrieved peer-reviewed research literature. RESULTS: Bioethanol
      production from lignocellulosic biomass can largely satisfy the possible
      inconsistency of first-generation ethanol since it utilizes inedible
      lignocellulosic feedstocks, primarily sourced from agriculture and forestry
      wastes. Two major polysaccharides in lignocellulosic biomass namely, cellulose
      and hemicellulose constitute a complex lignocellulosic network by connecting with
      lignin, which is highly recalcitrant to depolymerization. Several attempts have
      been made to reduce the cost involved in the process through improving the
      pretreatment process. While, the ligninolytic enzymes of white rot fungi (WRF)
      including laccase, lignin peroxidase (LiP), and manganese peroxidase (MnP) have
      appeared as versatile biocatalysts for delignification of several lignocellulosic
      residues. The first part of the review is mainly focused on engineering
      ligninolytic consortium. In the second part, WRF and its unique ligninolytic
      enzyme-based bio-delignification of lignocellulosic biomass, enzymatic
      hydrolysis, and fermentation of hydrolyzed feedstock are discussed. The metabolic
      engineering, enzymatic engineering, synthetic biology aspects for ethanol
      production and platform chemicals production are comprehensively reviewed in the
      third part. Towards the end information is also given on futuristic viewpoints.
      CONCLUSION: In conclusion, given the present unpredicted scenario of energy and
      fuel crisis accompanied by global warming, lignocellulosic bioethanol holds great
      promise as an alternative to petroleum. Apart from bioethanol, the simultaneous
      production of other value-added products may improve the economics of
      lignocellulosic bioethanol bioconversion process.

PMID- 29359653
TI  - Withdrawn: Impact of inhibitors on commercial cellulases in lignocellulosic
      ethanol production.

PMID- 29359654
TI  - Evaluating the Potential of Oleaginous Yeasts as Feedstock for Biodiesel
      Production.
AB  - BACKGROUND: Lipid-producing microorganisms, said to be oleaginous have been
      recognized since several years. We had investigated the effects of medium
      components and culturing situations on cell growth and lipid accumulation of
      oleaginous yeasts which were analytically examined so as to enhance lipid yield
      for biodiesel production. OBJECTIVE: The main objective of this study was to
      explore oleaginous yeast, Yarrowia lipolytica isolated from soil and optimization
      of culture conditions and medium components to obtained better quality microbial
      oil for biodiesel production. METHODS: Fifty yeast strains were isolated from
      soil from different regions of Lahore and eleven of them were selected for oil
      production. The isolated yeast colonies were screened to further check their
      lipid producing capabilities by the qualitative analysis. Five yeast strains were
      designated as oleaginous because they produced more than 16% of oil based on
      their biomass. To estimate the total lipid content of yeast cells, the extraction
      of lipids was done by performing the procedure proposed by Bligh and Dyer. The
      transesterification of yeast oils was performed by using different methods. There
      were three different strategies customized to transesterifying microbial oil
      using base catalyzed transesterification, acid catalyzed transesterification and
      enzyme-based transesterification. After completion of transesterification, sample
      was used for fatty acid methyl esters (FAMEs) were analyzed by gas-chromatograph
      with ionization detector type MS. RESULTS: The isolate IIB-10 identified as
      Yarrowia lipolytica produced maximum amount of lipids i.e. 22.8%. More amount of
      biomass was obtained when cane molasses was utilized as carbon source where it
      produced 29.4 g/L of biomass while sucrose and lactose were not utilized by IIB
      10 and no biomass was obtained. Similarly, meat extracts showed best results when
      it was used as nitrogen source because it resulted in 35.8 g/L biomass of
      Yarrowia lipolytica IIB-10. The culturing conditions like size of inoculum,
      effect of pH and time of incubation were also studied. The 10% of inoculum size
      produced 25.4 g/L biomass at 120 h incubation time, while the pH 7 was the
      optimum pH at which 24.8 g/L biomass was produced by Yarrowia lipolytica IIB-10.
      GC-MS analysis showed that biodiesel produced by transesterification contained
      similar fatty acids as found in vegetable oil for this reason it is widely
      accepted feedstock for biodiesel production. CONCLUSION: The analysis of fatty
      acids methyl esters showed the similar composition of microbial oil as in
      vegetable oils and high amount of methyl esters were obtained after
      transesterification. Therefore, potentially oleaginous yeast could be used to
      generate a large amount of lipids for biodiesel production that will be the
      better substitute of petroleum-based diesel and will also control the
      environmental pollution.

PMID- 29359655
TI  - Chloroplasts as Cellular Factories for the Cost-effective Production of
      Cellulases.
AB  - Chloroplasts are vital photosynthetic organelles in plant cells that carry out
      several important cellular functions including synthesis of amino acids, fatty
      acids, and lipids and metabolism of nitrogen, starch, and Sulphur to sustain the
      homeostasis in plants. These organelles have got their own genome, and related
      genetic machinery to synthesize required proteins for various plant functions.
      Genetic manipulations of the chloroplast genome for different biotech
      applications has been of great interest due to desired features including the
      availability of operonal mode of gene expression, high copy number, and maternal
      mode of inheritance (in the most field crops). Their capacity to often express
      transgenes at high levels make it a cost-effective platform for the production of
      foreign proteins, particularly high-value targets of industrial importance, at
      large scale. This article reviews briefly the research work carried out to
      produce cellulolytic enzymes in higher plant chloroplasts. The challenges and
      future opportunities for the same are also discussed.

PMID- 29359656
TI  - Enzymes: Plant-based Production and their Applications.
AB  - BACKGROUND: Enzymes are biocatalysts that play key roles in the production of
      biomolecules. Transgenic plants can be valuable cost effective resource to
      produce enzymes with bona fide structure. Further, plants provide inexpensive
      production platforms for pharmaceuticals and nutraceuticals. OBJECTIVE: This
      review article summarizes the properties and importance of enzymes and describes
      how foreign proteins/enzymes accumulate in plant cells that can be used for
      commercial purposes. CONCLUSION: The instances illustrated in this review
      evidently depict that plant enzymes involved in fundamental cellular activities
      are of great importance regarding plant growth and development. Investigating
      these enzymes and the metabolic pathways involved in their synthesis will
      certainly help to improve plant and human health. Furthermore, enzymes of
      industrial and pharmaceutical importance can be expressed in genetically modified
      plants to obtain enhanced expression. Considering easiness of obtaining desired
      expression, GM plants can offer a good alternate for large scale production of
      enzymes.

PMID- 29359657
TI  - Heterologous Synthesis and Recovery of Advanced Biofuels from Bacterial Cell
      Factories.
AB  - BACKGROUND: Microbial engineering to produce advanced biofuels is currently the
      most encouraging approach in renewable energy. Heterologous synthesis of biofuels
      and other useful industrial chemicals using bacterial cell factories has
      radically diverted the attentions from the native synthesis of these compounds.
      However, recovery of biofuels from the media and cellular toxicity are the main
      hindrances to successful commercialization of advanced biofuels. Therefore,
      membrane transporter engineering is gaining increasing attentions from all over
      the world. OBJECTIVE: The main objective of this review is to explore the ways to
      increase the microbial production of biofuels by counteracting the cellular
      toxicity and facilitating their easier recovery from media. CONCLUSION: Microbial
      synthesis of industrially viable compounds such as biofuels has been increased
      due to genomic revolution. Moreover, advancements in protein engineering, gene
      regulation, pathway portability, metabolic engineering and synthetic biology led
      the focus towards the development of robust and cost-effective systems for
      biofuel production. The most convenient way to combat cellular toxicity and to
      secrete biofuels is the use of membrane transport system. The use of membrane
      transporters is currently a serious oversight as do not involve chemical changes
      and contribute greatly to efflux biofuels in extracellular milieu. However,
      overexpression of transport systems can also be detrimental to cell, so, in
      future, structure-based engineering of transporters can be employed to evaluate
      optimum expression range, to increase biofuel specificity and transport rate
      through structural studies of biofuel molecules.

PMID- 29359658
TI  - Improving Xylose Utilization of Saccharomyces cerevisiae by Expressing the MIG1
      Mutant from the Self-Flocculating Yeast SPSC01.
AB  - BACKGROUND: The major carbohydrate components of lignocellulosic biomass are
      cellulose and hemicelluloses. Saccharomyces cerevisiae cannot efficiently utilize
      xylose derived upon the hydrolysis of hemicelluloses. Although engineering the
      yeast with xylose metabolic pathway has been intensively studied, challenges are
      still ahead for developing robust strains for lignocellulosic bioethanol
      production. OBJECTIVE: The main objective of this study was to reveal the role of
      the MIG1 mutant isolated from the self-flocculating S. cerevisiae SPSC01 in
      xylose utilization, glucose repression and ethanol fermentation by S. cerevisiae.
      METHODS: The MIG1 mutant was amplified from S. cerevisiae SPSC01 by PCR and MIG1-
      overexpression-cassette was transformed into S. cerevisiae S288c and xylose
      metabolizing strain YB-2625-T through homologous recombination. Yeast growth was
      measured by colony assay on plates with or without xylose supplementation. Then
      xylose utilization and ethanol production were further evaluated through flask
      fermentation when mixed sugars of glucose and xylose at 3:1 and 2:1,
      respectively, were supplied. Fermentation products were detected by HPLC, and
      activities of xylose reductase (XR), xylitol dehydrogenase (XDH) and xylulokinase
      (XK) were also measured. The transcription of genes regulated by the expression
      of the MIG1 mutant was analyzed by RTqPCR. Evolutionary relationship of various
      MIG1s was developed by gene sequencing and sequence alignment. RESULTS: No
      difference was observed for S288c growing with xylose when it was engineered with
      the overexpression or deletion of its native MIG1, but its growth was enhanced
      when overexpressing the MIG1 mutant from SPSC01. The submerged culture of YB-2625
      T MIG1-SPSC engineered with xylose-metabolic pathway and the MIG1 mutant
      indicated that xylitol accumulation was decreased, and consequently, more biomass
      was accumulated. Furthermore, improved activities of the key enzymes such as XR,
      XDH and XK were detected in YB-2625-T MIG1-SPSC. Evolutionary analysis of MIG1s
      amplified from S. cerevisiae strains commonly used for ethanol production
      revealed a close relationship of SPSC01 and YB-2625. CONCLUSION: Our results
      demonstrated the effect of the overexpression of the MIG1 mutant from SPSC01 on
      xylose utilization of S. cerevisiae. This study could be an alternative strategy
      for engineering S. cerevisiae with improved xylose utilization.

PMID- 29359659
TI  - Lignocellulosic Biomass: A Sustainable Bioenergy Source for the Future.
AB  - BACKGROUND: Increasing population and industrialization are continuously
      oppressing the existing energy resources and depleting the global fuel
      reservoirs. The elevated pollutions from the continuous consumption of non
      renewable fossil fuels also seriously contaminating the surrounding environment.
      The use of alternate energy sources can be an environment-friendly solution to
      cope these challenges. Among the renewable energy sources biofuels (biomass
      derived fuels) can serve as a better alternative to reduce the reliance on non
      renewable fossil fuels. Bioethanol is one of the most widely consumed biofuels of
      today's world. OBJECTIVE: The main objective of this review is to highlight the
      significance of lignocellulosic biomass as a potential source for the production
      of biofuels like bioethanol, biodiesel or biogas. METHODS: We discuss the
      application of various methods for the bioconversion of lignocellulosic biomass
      to end products i.e. biofuels. The lignocellulosic biomass must be pretreated to
      disintegrate lignocellulosic complexes and to expose its chemical components for
      downstream processes. After pretreatment, the lignocellulosic biomass is then
      subjected to saccharification either via acidic or enzymatic hydrolysis.
      Thereafter, the monomeric sugars resulted from hydrolysis step are further
      processed into biofuel i.e. bioethanol, biodiesel or butanol etc. through the
      fermentation process. The fermented impure product is then purified through the
      distillation process to obtain pure biofuel. CONCLUSION: Renewable energy sources
      represent the potential fuel alternatives to overcome the global energy crises in
      a sustainable and eco-friendly manner. In future, biofuels may replenish the
      conventional non-renewable energy resources due to their renewability and several
      other advantages. Lignocellulosic biomass offers the most economical biomass to
      generate biofuels. However, extensive research is required for the commercial
      production of an efficient integrated biotransformation process for the
      production of lignocellulose mediated biofuels.

PMID- 29359660
TI  - Colchicine in Renal Diseases: Present and Future.
AB  - Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and
      anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the
      disruption of the microtubule system and the inhibition of neutrophil adhesion
      and recruitment. Colchicine is indicated in the prevention and treatment of gouty
      arthritis and familial Mediterranean fever. In this review, we summarize current
      and potentially future pharmacologic activities of colchicine in various renal
      disease entities along with pharmacokinetic and pharmacodynamic properties.
      Additionally, we will refer to main interactions of colchicine with medications
      used in renal medicine, as well as dosing recommendations in patients with
      reduced glomerular filtration rate.

PMID- 29359661
TI  - Colchicine Pharmacokinetics and Mechanism of Action.
AB  - Colchicine is a tricyclic, lipid-soluble alkaloid derived from the plant of the
      Lily family Colchicum autumnale, sometimes called the "autumn crocus". It is
      predominantly metabolized in the gastrointestinal tract. Two proteins, P
      glycoprotein (P-gp) and CYP3A4 seem to play a pivotal role, governing its
      pharmacokinetic. The commonest side effects are gastrointestinal (nausea,
      vomiting and particularly dose-related-diarrhea) occurring in 5-10% of patients.
      Colchicine exerts its unique action mainly through inhibition of microtubule
      polymerization. Microtubule polymerization affects a variety of cellular
      processes including maintenance of shape, signaling, division, migration, and
      cellular transport. Colchicine interferes with several inflammatory pathways
      including adhesion and recruitment of neutrophils, superoxide production,
      inflammasome activation, the RhoA/Rho effector kinase (ROCK) pathway and the
      tumor necrosis factor alpha (TNF-alpha) -induced nuclear factor kappaBeta (NF
      kappaBeta) pathway attenuating the inflammatory response. This concise paper
      attempts to give a brief review of its pharmacokinetic properties and its main
      mechanisms of action.

PMID- 29359662
TI  - Inflammatory Arthritis and Heart Disease.
AB  - BACKGROUND: The term inflammatory joint disease (IJD) includes a group of chronic
      conditions, particularly rheumatoid arthritis (RA), ankylosing spondylitis (AS)
      and psoriatic arthritis (PsA), with predominant joint involvement and increased
      risk of cardiovascular (CV) complications and premature mortality. OBJECTIVE: The
      study aims to review of the most relevant CV manifestations from clinical point
      of view associated with IJD. METHODS: To update the current knowledge on CV
      manifestations in patients with IJD, we review the most relevant literature
      studies published in English (PubMed database) from January 2007 to February
      2017. RESULTS: Ischemic heart disease and congestive heart failure are the most
      relevant complications and those causing higher mortality. Pericarditis and
      myocarditis may be seen in patients with RA, especially in flares of disease,
      although they are often asymptomatic. Left ventricular diastolic ventricular
      dysfunction is an increasing recognized problem. Arrhythmias and cardiac
      conduction disturbances may be observed in patients with IJD. Chronic
      inflammation and fibrosis of the cardiac conduction system may be responsible for
      these complications. Noninvasive diagnostic tools including cardiac magnetic
      resonance imaging and echocardiography have improved considerably our
      understanding of the cardiovascular disease in IJD. CONCLUSION: Cardiac
      manifestations in IJD are frequent and they are the leading cause of an increased
      morbimortality in IJD. Clinicians would be aware of that, given that early
      diagnosis of these complications may reduce the frequency of CV events and
      improve survival of patients with IJD.

PMID- 29359663
TI  - A Review of the Clinical, Radiological and Biochemical Characteristics and
      Genetic Causes of High Bone Mass Disorders.
AB  - BACKGROUND: High bone mass (HBM) disorders are a group of clinically and
      genetically heterogeneous bone diseases characterized by increased bone density
      on radiographs, due to progressive bone overgrowth or impaired bone resorption,
      or both. Some HBM cases are secondary to other diseases, such as chronic
      hepatitis C virus infection. Despite the great advance in gene diagnostic
      technology, the majority of HBM individuals remain undiagnosed. OBJECTIVE: In
      this review, we will summarize the clinical, radiological and biochemical
      characteristics of HBM cases due to varying etiologies, since these features are
      helpful in the differential diagnosis of HBM. RESULTS: Each subgroup of HBM cases
      shows distinctive clinical, radiological and biochemical characteristics. HBM,
      due to bone overgrowth, was designated as sclerosteosis, as a result of mutations
      located in genes critically involved in the Wnt/beta-catenin signal pathway.
      Mutations in genes encoding factors relevant to the differentiation and
      maturation of osteoclasts, or critical for the acidification and resorption of
      osteoclasts may lead to osteopetrosis. Hepatitis C associated osteosclerosis is
      characterized by a generalized increase in bone mass and markedly elevated serum
      levels of bone specific alkaline phosphatase. CONCLUSION: The clarification of
      the etiologies of HBM may have a breakthrough role in understanding the molecular
      mechanisms involved in bone metabolism and may provide new pathways for the
      intervention of osteoporosis.

PMID- 29359664
TI  - Hypoperfusion of the Aortic Wall Secondary to Degeneration of Adventitial Vasa
      Vasorum Causes Abdominal Aortic Aneurysms.
AB  - BACKGROUND: An abdominal aortic aneurysm (AAA), which affects approximately 10%
      of Japanese men aged >= 65 years, is frequently associated with hypertension,
      dyslipidemia, and other lifestyle- related diseases. The development of an AAA is
      attributed to chronic inflammation concomitant with arteriosclerotic changes.
      However, an accurate pathomechanism associated with AAA remains uncertain, and
      questions such as why only a particular group/percentage of patients with
      arteriosclerosis develop aneurysms and how diabetes suppresses aneurysm
      development remain unanswered. OBJECTIVE: We examined a novel mechanism to
      develop AAA based on histopathological findings following analysis of the human
      AAA tissues. Additionally, based on these findings, we developed a new animal
      model of AAA, in which the histopathological characteristics are similar to human
      AAA tissue. RESULTS: Recently, we identified stenosis of the vasa vasorum (VV) in
      aortic segments showing dilatation. The aorta is the largest artery in our
      circulatory system. Under physiological conditions, the inner layer of the aorta
      is nourished via direct diffusion of nutrients from the luminal blood flow,
      whereas the outer adventitia is primarily perfused by the VV. Therefore,
      hypoperfusion of the VV induces hypoxia and subsequent inflammation and tissue
      degeneration of the aortic wall, resulting in aneurysm formation. Based on these
      findings, we established an AAA animal model by reducing the blood flow through
      the VV to the aortic wall. AAA was successfully reproduced in our animal model.
      Histopathological findings in this model were indistinguishable from those
      observed in humans, and pronounced abnormality in lipid composition in blood
      vessel adventitia was also observed. CONCLUSION: Thus, hypoperfusion of the
      aortic wall appeared to be sufficient to cause inflammationinduced AAA. These
      findings may provide potential targets for novel therapeutics for the management
      of an AAA.

PMID- 29359665
TI  - Pathogenic and Therapeutic Significance of Angiotensin II Type I Receptor in
      Abdominal Aortic Aneurysms.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is a chronic degenerative
      inflammatory disease. Multi-factors including genetic, environmental and
      lifestyle factors determine the onsets and progression of AAAs. Currently
      surgical repair remains the only effective aneurysm treatment, but no
      pharmacological therapy is available for limiting further enlargement of small
      AAAs and fetal rupture. OBJECTIVE: This article is to review our current
      understanding of angiotensin II (Ang II) and its type 1 receptor (AT1) in AAA
      pathogenesis as well as the translational potential of AT1 receptor blocker (ARB)
      treatment for treating clinical AAA disease. RESULTS: While many pathways or
      molecules have been shown to associate with AAA formation and progression,
      accumulating evidence indicates the most significant importance of peptide
      hormone Ang II and its receptor AT1 in AAA pathogenesis and suggests the
      translational value of targeting inhibition of AT1 in treating clinical AAA
      disease. This review summarized the influences of AT1 deficiency and
      pharmacological ARB treatment on experimental AAAs. A discussion has also been
      made on whether and how ARB medication in AAA patients changes the natural course
      of clinical AAAs, including aneurysm enlargement rate, rupture and AAA-specific
      mortality. Additionally, we provided information on two registered clinical
      trials which are to test the efficacy of telmisartan and valsartan in limiting
      small AAA enlargement. CONCLUSION: Ang II/AT1 pathway plays a critical role in
      aneurysmal pathogenesis. Targeting AT1 via ARB will help establishing novel
      pharmacological therapies for limiting continuous enlargement of small AAAs in
      patients.

PMID- 29359666
TI  - Enhancing the Intestinal Permeation of the Chondroprotective Nutraceuticals
      Glucosamine Sulphate and Chondroitin Sulphate Using Conventional and Modified
      Liposomes.
AB  - BACKGROUND: Liposomes are promising systems for the delivery of macromolecules
      and poorly absorbed drugs, owing to their ability to compartmentalize drugs,
      their biodegradability and biocompatibility. OBJECTIVE: The aim of the present
      study was to formulate and evaluate conventional and modified glucosamine
      sulphate (GluS) and chondroitin sulphate (CS) liposomal formulations, to enhance
      their oral permeation for the treatment of osteoarthritis (OA). METHOD: Liposomal
      formulations were prepared by the thin-film hydration method using two types of
      phospholipids; Epikuron 200(c) and Epikuron 200(c) SH, and three permeation
      enhancers; poloxamer 407, cetylpyridinium chloride, and sodium deoxycholate. In
      vitro characterization of liposomal formulations was conducted in terms of
      entrapment efficiency, particle size, zeta potential, viscosity, physical
      stability and mucoadhesive strength. Surface morphology and vesicle shape, ex
      vivo intestinal permeation, and histopathological studies were further carried
      out on the selected formulation. RESULTS: Results showed that the liposomal
      formulation containing sodium deoxycholate was the most optimum formula, showing
      high entrapment efficiency (60.11% for GluS and 64.10% for CS) with a particle
      size of 4.40 um, zeta potential of -17.2 mV and viscosity of 2.50 cP. CONCLUSION:
      The aforementioned formula displayed the highest cumulative % permeated of GluS
      and CS through rabbit intestinal mucosa compared to the solution of drugs and
      other liposomal formulations (64.20% for GluS and 78.21% for CS) after 2 hours.
      There were no histopathological alterations in the intestinal tissue, suggesting
      the safety of the utilized liposomal formulation. In light of the above,
      liposomes can be considered promising oral permeation-enhancer system for GluS
      and CS, which is worthy of future bioavailability experimentation.

PMID- 29359667
TI  - Preparation and Characterization of Stable Nanosuspension for Dissolution Rate
      Enhancement of Furosemide: A Quality by Design (QbD) Approach.
AB  - BACKGROUND: Nano drug delivery systems have the potential to address the
      challenges of delivering BCS Class II and IV drugs like furosemide. The purpose
      of the current study is to prepare stable nanosuspension and investigate in vitro
      dissolution performance of the model compound furosemide using quality by design
      (QbD) approach. METHODS: Nanosuspension batches with uniform particle size were
      prepared for furosemide using the antisolvent precipitation method. A quality by
      design (Qbd) approach was explored to understand the impact of process parameters
      (stirring time, stirring speed, temperature, and injection rate) and material
      attributes (drug concentration, stabilizer type, drug: stabilizer ratio, and
      antisolvent: solvent ratio) on the quality attributes of furosemide
      nanosuspension using a full factorial experimental design. Multiple linear
      regression and ANOVA were employed to estimate and identify the critical process
      parameters and material attributes. Injection rate and stirring time were
      identified as the most critical process parameters' affecting the quality
      attributes of furosemide nanosuspension. RESULTS: Individual material attributes
      did not show significant impact on the average particle size of the nanocrystals,
      however two-way interactions between material attributes (stabilizer type/drug
      concentration and stabilizer type/antisolvent: solvent ratio) significantly
      affected nanosuspension particle size distribution. Solid state characterization
      (PXRD, DSC and SEM) did not exhibit any changes of physical form during
      preparation and optimization of the furosemide nanosuspension. Dissolution of the
      furosemide nanocrystals in gastric media was significantly higher than that
      observed for micronized furosemide suspension and raw furosemide powder.
      Stability study data suggests that optimized batches of furosemide
      nanosuspensions were stable for three months at 4 degrees C and ambient
      conditions. CONCLUSION: The antisolvent precipitation method can produce stable
      furosemide nanosuspensions with desirable quality attributes and enhancement of
      dissolution rate in the gastric medium as compared to the raw furosemide powder
      and microsuspension.

PMID- 29359668
TI  - Auditory Event-related Potentials in Mild Cognitive Impairment and Alzheimer's
      Disease.
AB  - BACKGROUND: Mild cognitive deficits are more likely to occur with increasing age,
      and become more pronounced for people diagnosed with mild cognitive impairment
      (MCI) and Alzheimer's disease (AD). Conventional methods to identify cognitive
      declines (i.e., neuropsychological testing and clinical judgment) can lead to
      false positive diagnoses of cognitive impairment. Tools such as
      electroencephalography (EEG) offer additional measures of cognitive processing,
      indexing the electrophysiological changes associated with aging, MCI and AD.
      OBJECTIVE: We reviewed the literature on EEG to determine if auditory event
      related potentials (ERPs) could distinguish between healthy aging, MCI, and AD.
      METHOD: We searched two electronic databases (Medline and PyscInfo) for articles
      published between January 2005 and April 2017. Articles were considered for
      review if they included: i) participants 60 years of age or older; ii) healthy
      older adults or those diagnosed with MCI or AD; iii) at least one auditory
      elicited ERP component. RESULTS: Our search revealed 1532 articles (800 after
      removing duplicates); 719 were excluded through title/abstract review, and of the
      81 remaining articles, 30 satisfied inclusion criteria. All studies compared
      cognitive function between at least two of the three selected populations. Our
      findings suggest that the P300 and N200 components may distinguish between
      healthy cognitive aging, MCI, and AD. CONCLUSION: ERPs may be sensitive to
      progressive cognitive changes due to MCI and AD. The P300 and N200 may help
      identify patients who are likely to progress from MCI to AD, and could be a
      valuable clinical tool.

PMID- 29359669
TI  - Bromelain Degrades Abeta1-42 Monomers and Soluble Aggregates: An In Vitro Study
      in Cerebrospinal Fluid of Alzheimer's Disease Patients.
AB  - BACKGROUND: Therapeutic approaches targeting amyloid beta42 (Abeta42) oligomers
      may represent a promising neuroprotective strategy for the prevention and
      treatment of Alzheimer's disease (AD). OBJECTIVE: In this study we evaluated the
      ability of bromelain, a plant cysteine protease derived from pineapple stems, to
      interact with synthetic Abeta42 monomers and oligomers. We also examined the
      ability of bromelain to interfere in vitro with synthetic Abeta42 aggregates in
      the cerebrospinal fluid (CSF) of Alzheimer's disease as well as of control
      patients affected by other neurological diseases. METHOD: Both synthetic monomers
      and aggregates of Abeta42 were incubated in CSF with varying concentrations of
      bromelain. The effects of digestion were evaluated by Western Blot analysis using
      the specific monoclonal antibody 4G8 to identify the patterns of residual content
      of Abeta42. We further used rat primary cortical culture neurons (CN) to examine
      the cytotoxic action of this natural compound. RESULTS: We found that bromelain
      successfully degraded Abeta42 monomers and low and high molecular weight
      oligomers. Indeed, when bromelain preparations of 3 and 6 mU were added to the
      CSF, the residual amount of Abeta42 monomers and oligomers were significantly
      reduced when compared to the same standard Abeta42 preparations incubated in CSF
      without bromelain. Moreover, bromelain incubations of 0.1, 0.5, and 1 mU/ml were
      not toxic to CN, as compared to vehicle treated cells. CONCLUSION: Overall, these
      results represent an important insight into the action of bromelain on Abeta42
      oligomers, suggesting its potential use in the therapy of AD.

PMID- 29359670
TI  - Drusen in the Peripheral Retina of the Alzheimer's Eye.
AB  - BACKGROUND: Recent work on Alzheimer's disease (AD) diagnosis focuses on
      neuroimaging modalities; however, these methods are expensive, invasive, and not
      available to all patients. Ocular imaging of biomarkers, such as drusen in the
      peripheral retina, could provide an alternative method to diagnose AD. OBJECTIVE:
      This study compares macular and peripheral drusen load in control and AD eyes.
      METHODS: Postmortem eye tissues were obtained from donors with a
      neuropathological diagnosis of AD. Retina from normal donors were processed and
      categorized into younger (<55 years) and older (>55 years) groups. After fixation
      and dissection, 3-6 mm punches of RPE/choroid were taken in macular and
      peripheral (temporal, superior, and inferior) retinal regions. Oil red O positive
      drusen were counted and grouped into two size categories: small (<63 MUm) and
      intermediate (63-125 MUm). RESULTS: There was a significant increase in the total
      number of macular and peripheral hard drusen in older, compared to younger,
      normal eyes (p<0.05). Intermediate hard drusen were more commonly found in the
      temporal region of AD eyes compared to older normal eyes, even after controlling
      for age (p<0.05). Among the brain and eye tissues from AD donors, there was a
      significant relationship between cerebral amyloid angiopathy (CAA) severity and
      number of temporal intermediate hard drusen (r=0.78, p<0.05). CONCLUSION: Imaging
      temporal drusen in the eye may have benefit for diagnosing and monitoring
      progression of AD. Our results on CAA severity and temporal intermediate drusen
      in the AD eye are novel. Future studies are needed to further understand the
      interactions among CAA and drusen formation.

PMID- 29359671
TI  - Does Perioperative Hemoglobin A1c Level Affect the Incidence, Pattern and
      Mortality of Lower Extremity Amputation?
AB  - We hypothesized that perioperative HbA1c influenced the pattern and outcomes of
      lower extremity amputation (LEA). A retrospective analysis was conducted for all
      patients who underwent LEA between 2000 and 2013. Patients were categorized into
      5 groups according to their perioperative HbA1c values [Group 1 (<6.5%), Group 2
      (6.5-7.4%), Group 3 (7.5-8.4%), Group 4 (8.5-9.4%) and Group 5 (>=9.5%)]. We
      identified 848 patients with LEA; perioperative HbA1c levels were available in
      547 cases (Group 1: 18.8%, Group 2: 17.7%, Group 3: 15.0%, Group 4: 13.5% and
      Group 5: 34.9%). Major amputation was performed in 35%, 32%, 22%, 10.8% and
      13.6%, respectively. The overall mortality was 36.5%; of that one quarter
      occurred during the index hospitalization. Mortality was higher in Group 1
      (57.4%) compared with Groups 2-5 (46.9%, 38.3%, 36.1% and 31.2%, respectively,
      p=0.001). Cox regression analysis showed that poor glycemic control (Group 4 and
      5) had lower risk of mortality post-LEA [hazard ratio 0.57 (95% CI 0.35-0.93) and
      hazard ratio 0.46 (95% CI 0.31-0.69)]; this mortality risk persisted even after
      adjustment for age and sex but was statistically insignificant. The rate of LEA
      was greater among poor glycemic control patients; however, the mortality was
      higher among patients with tight control. The effects of HbA1c on the immediate
      and long-term LEA outcomes and its therapeutic implications need further
      investigation.

PMID- 29359672
TI  - Is there Sex-related Outcome Difference according to oral P2Y12 inhibitors in
      Patients with Acute Coronary Syndromes? A Systematic Review and Meta-Analysis of
      107,126 Patients.
AB  - Background and objectives The majority of patients included in trials of anti
      platelet therapy are male. This systematic review and meta-analysis aimed to
      determine whether, in addition to aspirin, P2Y12 blockade is beneficial in both
      women and men with acute coronary syndromes. Methods Electronic databases were
      searched and nine eligible randomised controlled studies were identified that had
      sex-specific clinical outcomes (n=107,126 patients). Risk ratios (RR) and 95%
      confidence intervals (CI) were calculated for a composite of cardiovascular
      death, myocardial infarction or stroke (MACE), and a safety endpoint of major
      bleeding for each sex. Indirect comparison analysis was performed to
      statistically compare ticagrelor against prasugrel. Results Compared to aspirin
      alone, clopidogrel reduced MACE in men (RR, 0.79; 95% CI, 0.68 to 0.92; p=0.003),
      but was not statistically significant in women (RR, 0.88; 95% CI, 0.75 to 1.02,
      p=0.08). Clopidogrel therapy significantly increased bleeding in women but not
      men. Compared to clopidogrel, prasugrel was beneficial in men (RR, 0.84; 95% CI,
      0.73 to 0.97; p=0.02) but not statistically significant in women (RR, 0.94; 95%
      CI, 0.83 to 1.06; p=0.30); ticagrelor reduced MACE in both men (RR, 0.85; 95% CI,
      0.77 to 0.94; p=0.001) and women (RR, 0.84; 95% CI, 0.73 to 0.97; p=0.02).
      Indirect comparison demonstrated no significant difference between ticagrelor and
      prasugrel in either sex. Compared to clopidogrel, ticagrelor and prasugrel
      increased bleeding risk in both women and men. Conclusion In summary, in
      comparison to monotherapy with aspirin, P2Y12 inhibitors reduce MACE in women and
      men. Ticagrelor was shown to be superior to clopidogrel in both sexes. Prasugrel
      showed a statistically significant benefit only in men; however indirect
      comparison did not demonstrate superiority of ticagrelor over prasugrel in women.

PMID- 29359673
TI  - Non-traditional Cardiovascular Risk Markers in the Era of Established Major Risk
      Factors and Multiple Guidelines.
AB  - The non-traditional cardiovascular (CV) risk factors that appear to be of most
      clinical interest include: apolipoprotein A (ApoA), apolipoprotein B (ApoB), high
      sensitivity C-Reactive protein (hsCRP), homocysteine, interleukin 1 (IL1),
      lipoprotein (a) [Lp(a)], the density of low-density lipoprotein (LDL) particles,
      the LDL particle number, tissue/tumor necrosis factor-alpha (TNF-alpha) and uric
      acid. These non-traditional risk factors may be of value in adding further
      confirmation and attention to suspected significant CV risk. They can also
      provide a better understanding of current concepts of atherogenesis (e.g. various
      potential mechanisms associated with inflammation) as an etiology and in guiding
      current plus future therapies. In the mid-20th century, atherosclerosis and CV
      disease were considered mechanistic occurrences with essentially no attention to
      possible metabolic and molecular etiologies. Therefore, the only treatments then
      centered around mainly surgical procedures to try to improve blood flow, first
      with peripheral arterial disease (PAD) and later coronary artery disease (CAD).
      Now, failure to treat CV risk factors, especially where there is good evidence
      based medicine, as in the case of statins for high CV risk patients, is
      considered medical negligence. Nevertheless, many problems remain to be solved
      regarding atherosclerosis prevention and treatment.

PMID- 29359674
TI  - Patient adherence to Novel Oral Anticoagulants (NOACs) for the treatment of
      Atrial Fibrillation and occurrence of associated bleeding events: A Systematic
      Review and Meta-analysis.
AB  - AIM: Real-world evidence from published observational studies of adherence to
      novel oral anticoagulants (NOACs) medications and associated clinical outcome
      events in atrial fibrillation (AF) patients, was reviewed systematically.
      METHODS: Observational studies assessing patient adherence to NOACs conducted on
      AF patients between September 2010 and June 2016 were identified by systematic
      searching keywords to locate eligible studies, in accordance with Cochrane
      guidelines. PubMed, Scopus and Google Scholar databases were searched to identify
      the studies. Meta-analysis was performed using a random effects model with
      DerSimonian-Laird weighting to obtain pooled effect sizes. RESULTS: From 185
      potentially relevant citations, 6 studies, comprising 1.6 million AF patients,
      were included. Among these, successful adherence to NOACs occurred in 75.6%.
      Adherence levels were higher in patients treated with dabigatran (72.7%) compared
      with those treated with apixaban (59.9%) or rivaroxaban (59.3%). However,
      adherence was still suboptimal (relative to an expected 80% adherence rate).
      Bleeding events in non-adherent patients were found to be 7.5%. CONCLUSION:
      Suboptimal adherence to NOACs among AF patients was highlighted as a significant
      risk factor that may affect clinical outcomes, with a higher percentage of non
      adherent patients having bleeding events. There is an urgent need for research on
      the effects of specific interventions to improve patient adherence to NOACs and
      to assess the related outcome factors that may be associated with adherence.

PMID- 29359675
TI  - Consistency of Toe Systolic Pressures, Brachial Systolic Pressures, and Toe
      Brachial Indices in People with and without Diabetes.
AB  - BACKGROUND & AIMS: Toe systolic blood pressures (TSPs) and toe-brachial indices
      (TBIs) have been identified as useful adjuncts in the identification of pedal
      ischemia, peripheral artery occlusive diseases, and risk for either nonhealing of
      lower extremity wounds or for amputation. Valid measurement of TSPs and TBIs is
      therefore essential. However, it could be jeopardized by rater, instrument, and
      intratestee inconsistency. These three sources of inconsistency were examined in
      this research. METHODS: Five publications addressing TSP and TBI consistency were
      identified and their results were analyzed using intraclass correlation
      coefficients. RESULTS: Moderate variability in TSPs was found across all studies;
      greater variability was evidenced in brachial systolic pressure, particularly for
      people who had diabetes; and TBI values also exhibited considerable variability,
      but little difference between people who did and did not have diabetes.
      CONCLUSIONS: These findings provide qualified evidence of consistency regarding
      measurement of TSPs but challenge the TBI as a valid and useful indicator in
      screening, prognostic, and monitoring contexts, particularly for people who have
      diabetes. However, there is a prospect that TBI assessment could be improved by
      adherence to standardized protocols and by obtaining multiple measurements from
      toes and arms on a single occasion as well as on different occasions.

PMID- 29359676
TI  - Computational Exploration of Natural Compounds to Target Cytosolic Phospholipase
      A 2 Protein: A Novel Therapeutic Target for Spinal Cord Injury.
AB  - BACKGROUND: Cytosolic Phospholipase A2 (cPLA2), an important isoform of PLA2 that
      mediates the release of arachidonic acid, plays a role in the pathogenesis of
      Spinal Cord Injury (SCI). The expression and activation of Cpla2 are
      significantly higher in SCI, leading to neuronal death in spinal cord tissue.
      Novel strategies are needed to substantially reverse the effect of cPLA2
      activation; one such strategy is inhibiting cPLA2 by jamming its lipid binding C2
      domain. OBJECTIVE: To develop a much needed strategy to treat SCI, we used a
      Computer Aided Drug Design (CADD) method to discover novel cPLA2 inhibitors.
      METHODS: we used a natural chemiome database for virtual screening, from which we
      selected the compounds exhibiting the greatest drug-likeliness properties for
      molecular docking simulation analysis. RESULTS: We studied the interaction of
      lead compounds at the atomic level; the results yielded a cPLA2 inhibitor of
      natural origin with the potential for ameliorating secondary tissue damage and
      promoting recovery of function after SCI. The top compound, lead 4exibited a
      binding energy of -10.02 Kcal/mol and formed three hydrogen bonds with the lipid
      binding C2 domain of the cPLA2 protein. An evaluation of cell cytotoxicity
      revealed an IC50 for lead4 of 134.2 +/- 6.8 uM. An in-vitro analysis of lead4 is
      indicated anti-apoptotic activity via a decrease in caspase-3 expression.
      CONCLUSION: We used the CADD method to make a novel lead discovery for the
      treatment of SCI using compounds of natural origin. The selected natural
      compounds are non-toxic promising drugs against cPLA2 protein, allowing us to
      limits our focus on single compound for future in-vitro and invivo testing.

PMID- 29359677
TI  - Comparative Randomized Crossover Clinical Study for the Evaluation of Erectile
      Dysfunction Medications Via Novel Pentagon System.
AB  - INTRODUCTION: Due to the chaos in the legislation in the Middle East, male
      enhancement nutraceuticals may be sold without any registration or evaluation.
      These products need to be evaluated with respect to safety and efficacy.
      Furthermore, cultural and social considerations in the Middle East prevent the
      use of international evaluations schemes for erectile dysfunction. AIM:
      Evaluating the safety and efficacy parameters of generic and nutraceutical
      products for erectile dysfunction in the Middle East through a custom-designed,
      representable and simple system tailored to the regional culture. METHODS: 74
      healthy male volunteers were enrolled into a comparative, simple randomized,
      single dose, double blind, and crossover clinical study incorporated with a
      tailored-designed questionnaire. Safety assessment included laboratory analysis
      for liver functions and measuring blood pressure. MAIN OUTCOME MEASURES:
      Subjective data regarding safety and efficacy were assessed from the validated
      questionnaire. Blood pressure was measured. Blood samples were collected to
      assess the drug/adulterants concentration and liver and kidney functions.
      RESULTS: All tested nutraceuticals showed undeclared Sildenafil citrate in
      patients. Questionnaire results showed high inter-patient variability with
      respect to efficacy and comparable safety profile compared to Viagra(r).
      CONCLUSION: The validated tailored-designed questionnaire effectively assessed
      the efficacy and safety of male enhancement products. The male enhancement
      nutraceuticals, sold in Egypt, claimed to be 100% natural are adulterated and of
      questionable safety profile.

PMID- 29359678
TI  - Different Sources of Stem Cells and their Application in Cartilage Tissue
      Engineering.
AB  - BACKGROUND: The articular cartilage is unique in that it contains only a single
      type of cell and shows poor ability for spontaneous healing. Currently,
      approaches for treating cartilage defects include surgical and nonsurgical
      approaches, as well as cartilage tissue engineering. For standard cartilage
      tissue engineering, three elements are required, i.e., a scaffold, growth
      factors, and seed cells. With advancements in stem cell research, the main
      sources of cells for cartilage tissue engineering are embryonic and mesenchymal
      stem cells, which have been shown to be promising alternatives in recent years.
      OBJECTIVE: In this review, we focus on the applications of various stem cells in
      cartilage tissue engineering. RESULTS: Under certain conditions, several types of
      stem cells, including embryonic stem cells, mesenchymal stem cells, induced
      pluripotent stem cells, and cartilage progenitor cells, showed potential for
      applications in chondrogenic differentiation. CONCLUSION: Stem cells can be
      developed as important cell sources for cartilage tissue engineering if
      appropriate microenvironments and bioactive factors are supplied. However,
      further studies are needed to determine the ideal cell type for cartilage repair,
      particularly using in vivo and clinical studies.

PMID- 29359679
TI  - Emerging Metabolomics Biomarkers of Polycystic Ovarian Syndrome; Targeting the
      Master Metabolic Disrupters for Diagnosis and Treatment.
AB  - BACKGROUND AND OBJECTIVE: Metabolomics is a powerful exploratory tool for
      discovering new diagnostic molecules or biomarkers due to its ability to
      highlight several interactions between different biochemical molecules and
      pathways in composition in health and disease thereby advancing our
      understanding, to provide evidence based diagnosis and treatment of such a
      complex disease including polycystic ovarian syndrome (PCOS). The aim of this
      study was to review available literature on the use of metabolomic approach and
      to critically evaluate and draw a synthesis to highlight novel biochemical
      markers for clinical application in PCOS. METHOD: Studies that applied
      metabolomic approach to investigate PCOS and those meeting selection criteria
      were searched and, critically evaluated. RESULT: Here we highlighted the
      metabolic reactions and perturbation of some metabolic pathways present in
      patients with polycystic ovarian syndrome and normal subjects that can allow
      better understanding of the disorder and help developing a new generation
      diagnostic and treatment algorithm. CONCLUSION: A number of disease-related
      metabolites have been discussed which have extraordinary potential for a clinical
      utility as diagnostic and treatment monitoring biomarkers.

PMID- 29359680
TI  - Withdrawn: Novel Ternary Polymeric Blends for Controlled Release Matrices
      Containing Weakly Basic Model Drug.

PMID- 29359681
TI  - Involvement of NLRP3 inflammasome in the impacts of sodium and potassium on
      insulin resistance in normotensive Asians.
AB  - Salt, promoting oxidative stress, contributes to insulin resistance, whereas K,
      inhibiting oxidative stress, improves insulin sensitivity. Oxidative stress
      activation of NLRP3 inflammasome is a central player in the induction of insulin
      resistance. Therefore, we hypothesised that NLRP3 inflammasome may mediate the
      effects of salt and K on insulin resistance. In all, fifty normotensive subjects
      were recruited from a rural community of Northern China. The protocol included a
      low-salt diet for 7 d, then a high-salt diet for 7 d and a high-salt diet with K
      supplementation for another 7 d. In addition, THP-1 cells were cultured in
      different levels of Na with and without K. The results showed that salt loading
      elevated fasting blood glucose, insulin and C-peptide levels, as well as insulin
      resistance, whereas K supplementation reversed them. Meanwhile, additional K
      reversed the active effects of high salt on NLRP3 inflammasome in both the
      subjects and THP-1 cells, and the change of insulin resistance index notably
      related with the alteration of plasma IL-1beta, the index of NLRP3 inflammasome
      activation, during intervention in the subjects. Additional K ameliorated
      oxidative stress induced by high salt in both the subjects and cultured THP-1
      cells, and the change of oxidative stress related with the alteration of plasma
      IL-1beta during intervention in the subjects. In vitro, antioxidant N-acetyl-l
      cysteine significantly prevented the active effects of high Na or oxidant Rosup
      on NLRP3 inflammasome, so did K. Our study indicates that oxidative stress
      modulation of NLRP3 inflammasome may be involved in the impacts of Na and K on
      insulin resistance.

PMID- 29359682
TI  - Fatty acid transport receptor soluble CD36 and dietary fatty acid pattern in type
      2 diabetic patients: a comparative study.
AB  - Recently, it has been remarked that dietary fatty acids and fatty acid receptors
      might be involved in the aetiology of diabetes. Therefore, this study was
      conducted to determine the relationship between dietary fatty acid pattern, fatty
      food preferences and soluble CD36 (sCD36) and insulin resistance in type 2
      diabetes mellitus (DM). The study was carried out with thirty-eight newly
      diagnosed type 2 DM patients and thirty-seven healthy volunteers, aged 30-65
      years. In the study, socio-demographic characteristics, dietary fat type and
      fatty acid pattern of individuals were recorded. After anthropometric
      measurements were taken, blood CD36, glucose, TAG and insulin levels were
      analysed. The results showed that although the type of fatty acid intake did not
      differ between the groups (P>0.05), the consumption of olive oil in the type 2 DM
      group was lower than the control group (P0.05). Crucially, elevated sCD36 levels
      increased the type 2 DM risk (OR 1.21, P<0.05). In conclusion, sCD36 level may be
      a possible biomarker, independent from the dietary fatty acid pattern, for type 2
      DM owing to its higher levels in these patients. Therefore, the new insights make
      CD36 attractive as a therapeutic target for diabetes.

PMID- 29359684
TI  - Invited commentary in response to PUFA status at birth and allergy-related
      phenotypes in childhood: a pooled analysis of the Maastricht Essential Fatty Acid
      Birth and Rhea birth cohorts.

PMID- 29359683
TI  - PUFA status at birth and allergy-related phenotypes in childhood: a pooled
      analysis of the Maastricht Essential Fatty Acid Birth (MEFAB) and RHEA birth
      cohorts.
AB  - Lower prenatal exposure to n-3 PUFA relative to n-6 PUFA has been hypothesised to
      influence allergy development, but evidence remains largely inconsistent. In the
      Dutch Maastricht Essential Fatty Acid Birth (MEFAB) (n 293) and Greek RHEA Mother
      Child (n 213) cohorts, we investigated whether cord blood phospholipid PUFA
      concentrations are associated with symptoms of wheeze, asthma, rhinitis and
      eczema at the age of 6-7 years. Information on allergy-related phenotypes was
      collected using validated questionnaires. We estimated relative risks (RR) and 95
      % CI for associations of PUFA with child outcomes using multivariable generalised
      linear regression models. In pooled analyses, higher concentration of the n-3
      long-chain EPA and DHA and a higher total n-3:n-6 PUFA ratio were associated with
      lower risk of current wheeze (RR 0.61; 95 % CI 0.45, 0.82 per sd increase in
      EPA+DHA and 0.54; 95 % CI 0.39, 0.75 per unit increase in the n-3:n-6 ratio) and
      reduced asthma risk (RR 0.50; 95 % CI 0.31, 0.79 for EPA+DHA and 0.43; 95 % CI
      0.26, 0.70 for the n-3:n-6 ratio). No associations were observed for other
      allergy-related phenotypes. The results were similar across cohorts. In
      conclusion, higher EPA and DHA concentrations and a higher n-3:n-6 fatty acid
      ratio at birth were associated with lower risk of child wheeze and asthma. Our
      findings suggest that dietary interventions resulting in a marked increase in the
      n-3:n-6 PUFA ratio, and mainly in n-3 long-chain PUFA intake in late gestation,
      may reduce the risk of asthma symptoms in mid-childhood.

PMID- 29359685
TI  - Cleavage activates dispatched for Sonic Hedgehog ligand release.
AB  - Hedgehog ligands activate an evolutionarily conserved signaling pathway that
      provides instructional cues during tissue morphogenesis, and when corrupted,
      contributes to developmental disorders and cancer. The transmembrane protein
      Dispatched is an essential component of the machinery that deploys Hedgehog
      family ligands from producing cells, and is absolutely required for signaling to
      long-range targets. Despite this crucial role, regulatory mechanisms controlling
      Dispatched activity remain largely undefined. Herein, we reveal vertebrate
      Dispatched is activated by proprotein convertase-mediated cleavage at a conserved
      processing site in its first extracellular loop. Dispatched processing occurs at
      the cell surface to instruct its membrane re-localization in polarized epithelial
      cells. Cleavage site mutation alters Dispatched membrane trafficking and reduces
      ligand release, leading to compromised pathway activity in vivo. As such,
      convertase-mediated cleavage is required for Dispatched maturation and functional
      competency in Hedgehog ligand-producing cells.

PMID- 29359686
TI  - Targeting RAS-driven human cancer cells with antibodies to upregulated and
      essential cell-surface proteins.
AB  - While there have been tremendous efforts to target oncogenic RAS signaling from
      inside the cell, little effort has focused on the cell-surface. Here, we used
      quantitative surface proteomics to reveal a signature of proteins that are
      upregulated on cells transformed with KRASG12V, and driven by MAPK pathway
      signaling. We next generated a toolkit of recombinant antibodies to seven of
      these RAS-induced proteins. We found that five of these proteins are broadly
      distributed on cancer cell lines harboring RAS mutations. In parallel, a cell
      surface CRISPRi screen identified integrin and Wnt signaling proteins as critical
      to RAS-transformed cells. We show that antibodies targeting CDCP1, a protein
      common to our proteomics and CRISPRi datasets, can be leveraged to deliver
      cytotoxic and immunotherapeutic payloads to RAS-transformed cancer cells and
      report for RAS signaling status in vivo. Taken together, this work presents a
      technological platform for attacking RAS from outside the cell.

PMID- 29359687
TI  - Microbial Biomass and Enzymatic Activity of the Surface Microlayer and Subsurface
      Water in Two Dystrophic Lakes.
AB  - Nutrient and organic matter concentration, microbial biomass and activities were
      studied at the surface microlayers (SML) and subsurface waters (SSW) in two small
      forest lakes of different water colour. The SML in polyhumic lake is more
      enriched with dissolved inorganic nitrogen (0.141 mg l-1) than that of oligohumic
      lake (0.124 mg l-1), the former also contains higher levels of total nitrogen
      (2.66 mg l-1). Higher activities of lipase (Vmax 2290 nmol l-1 h-1 in oligo- and
      6098 in polyhumic) and glucosidase (Vmax 41 nmol l-1 h-1 in oligo- and 49 in
      polyhumic) were in the SMLs in both lakes. Phosphatase activity was higher in the
      oligohumic SML than in SSW (Vmax 632 vs. 339 nmol l-1 h-1) while in polyhumic
      lake was higher in SSW (Vmax 2258 nmol l-1 h-1 vs. 1908 nmol l-1 h-1).
      Aminopeptidase activity in the SSW in both lakes was higher than in SMLs (Vmax
      2117 in oligo- and 1213 nmol l-1 h-1 in polyhumic). It seems that solar radiation
      does inhibit neuston microbial community as a whole because secondary production
      and the share of active bacteria in total bacteria number were higher in SSW.
      However, in the oligohumic lake the abundance of bacteria in the SML was always
      higher than in the SSW (4.07 vs. 2.69 * 106 cells ml-1) while in the polyhumic
      lake was roughly equal (4.48 vs. 4.33 * 106 cells ml-1) in both layers. Results
      may also suggest that surface communities are not supplemented by immigration
      from bulk communities. The SML of humic lakes may act as important sinks for
      allochthonous nutrient resources and may then generate considerable energy pools
      for microbial food webs.

PMID- 29359688
TI  - Screening and Identification of Yeasts Antagonistic to Pathogenic Fungi Show a
      Narrow Optimal pH Range for Antagonistic Activity.
AB  - Microbes have evolved ways of interference competition to gain advantage over
      their ecological competitors. The use of secreted antagonistic compounds by yeast
      cells is one of the prominent examples. Although this killer behavior has been
      thoroughly studied in laboratory yeast strains, our knowledge of the antagonistic
      specificity of killer effects in nature remains limited. In this study, yeast
      strains were collected from various niches and screened for antagonistic activity
      against one toxin-sensitive strain of Saccharomyces cerevisiae and three
      pathogenic fungi. We demonstrate that some strains with antagonistic activity
      against these pathogenic fungi can be found in antagonist culture tests. These
      yeasts were identified as members of Trichosporon asahii, Candida stellimalicola,
      Wickerhamomyces anomalus, Ustilago esculenta, Aureobasidium pullulans, and Pichia
      kluyveri. The results indicated that the antagonistic activity of these killer
      yeasts has a narrow optimal pH range. Furthermore, we found that the antagonistic
      activity of some species is strain-dependent.

PMID- 29359689
TI  - Application of Metagenomic Analyses in Dentistry as a Novel Strategy Enabling
      Complex Insight into Microbial Diversity of the Oral Cavity.
AB  - The composition of the oral microbiome in healthy individuals is complex and
      dynamic, and depends on many factors, such as anatomical location in the oral
      cavity, diet, oral hygiene habits or host immune responses. It is estimated at
      present that worldwide about 2 billion people suffer from diseases of the oral
      cavity, mainly periodontal disease and dental caries. Importantly, the oral
      microflora involved in local infections may spread and cause systemic, even life
      threatening infections. In search for etiological agents of infections in
      dentistry, traditional approaches are not sufficient, as about 50% of oral
      bacteria are not cultivable. Instead, metagenomic analyses are particularly
      useful for studies of the complex oral microbiome - both in healthy individuals,
      and in patients with oral and dental diseases. In this paper we review the
      current and future applications of metagenomic studies in evaluation of both the
      composition of the oral microbiome as well as its potential pathogenic role in
      infections in dentistry.

PMID- 29359690
TI  - From Latent Tuberculosis Infection to Tuberculosis. News in Diagnostics
      (QuantiFERON-Plus).
AB  - It is estimated that one third of the world's population have latent tuberculosis
      infection and that this is a significant reservoir for future tuberculosis cases.
      Most cases occur within two years following initial infection. The identification
      of individuals with latent tuberculosis infection is difficult due to the lack of
      an ideal diagnostic assay and incomplete understanding of latent infection.
      Currently, there are three tests: the oldest tuberculin skin test, T-SPOT.TB and
      the latest QuantiFERON-Plus for the detection of Mycobacterium tuberculosis
      infection. The interpretation of the test results must be used in the conjunction
      with a patient's epidemiological history, risk assessment, current clinical
      status, radiography and microbiological methods to ensure accurate diagnosis.

PMID- 29359691
TI  - Dipicolinic Acid Release and the Germination of Alicyclobacillus acidoterrestris
      Spores under Nutrient Germinants.
AB  - The presence of Alicyclobacillus, a thermoacidophilic and spore-forming
      bacterium, in acidic fruit juices poses a serious problem for the processing
      industry. A typical sign of spoilage in contaminated juices is a characteristic
      phenolic off-flavour associated with the production of guaiacol. Spores are
      formed in response to starvation and in a natural environment re-access the
      nutrients, e.g.: L-alanine and AGFK - a mixture of asparagine, glucose, fructose
      and potassium, triggers germination. The aim of this study was to estimate the
      impact of L-alanine and AGFK on the germination of the spores of two
      Alicyclobacillus acidoterrestris strains and to evaluate the relationship of the
      germination rate with dipicolinic acid (DPA) release. The spores were suspended
      in apple juice or in buffers at pH 4 and pH 7, followed by the addition of L
      alanine and AGFK. Suspensions were or were not subjected, to a temperature of 80
      degrees C/10 min and incubated for various periods of time at 45 degrees C.
      Optical density (OD660) was used to estimate the number of germinated spores. The
      amount of DPA released was determined using HPLC. The results indicate that the
      degree of germination of A. acidoterrestris spores depended on the strain and
      time of incubation and the nutritious compounds used. The data obtained show that
      the amount of DPA released correlated to the number of A. acidoterrestris spores
      germinated.

PMID- 29359692
TI  - Expression of the Fluoroquinolones Efflux Pump Genes acrA and mdfA in Urinary
      Escherichia coli Isolates.
AB  - Escherichia coli is one of the most frequent causes of urinary tract infections.
      Efflux system overexpression is reported to contribute to E. coli resistance to
      several antibiotics. Our aim in this study was to investigate the relation
      between antibiotic resistance and the expression of the efflux pump genes acrA
      and mdfA in E. coli by real-time reverse transcription-PCR. We tested the in
      vitro susceptibilities to 12 antibiotics in 28 clinical isolates of E. coli
      obtained from urine samples. We also determined the minimum inhibitory
      concentrations of levofloxacin to these samples. We then revealed significant
      correlations between the overexpression of both mdfA and acrA and MICs of
      levofloxacin. In conclusion, we demonstrated that the increased expression of
      efflux pump genes such as mdfA and acrA can lead to levofloxacin resistance in E.
      coli. These findings contribute to further understanding of the molecular
      mechanisms of efflux pump systems and how they contribute to antibiotic
      resistance.

PMID- 29359693
TI  - Vital Staining of Bacteria by Sunset Yellow Pigment.
AB  - In this study, we describe a method for discriminating pathogenic bacteria with a
      dye. First, we determined that among several colours tested, the sunset yellow
      pigment easily coloured Escherichia coli bacteria yellow. Next, we demonstrated
      that E. coli O157:H7, Shigella flexneri O301, Staphylococcus aureus and Bacillus
      subtilis could all be well marked by sunset yellow pigment. Finally, we performed
      bacterial viability assays and found there was no effect on bacterial growth when
      in co-culture with sunset yellow. Our results suggest that sunset yellow is
      suitable pigment to dye microorganisms.

PMID- 29359695
TI  - Use of Amplification Fragment Length Polymorphism to Genotype Pseudomonas
      stutzeri Strains Following Exposure to Ultraviolet Light A.
AB  - Changes in ultraviolet light radiation can act as a selective force on the
      genetic and physiological traits of a microbial community. Two strains of the
      common soil bacterium Pseudomonas stutzeri, isolated from aquifer cores and from
      human spinal fluid were exposed to ultraviolet light. Amplification length
      polymorphism analysis (AFLP) was used to genotype this bacterial species and
      evaluate the effect of UVA-exposure on genomic DNA extracted from 18 survival
      colonies of the two strains compared to unexposed controls. AFLP showed a high
      discriminatory power, confirming the existence of different genotypes within the
      species and presence of DNA polymorphisms in UVA-exposed colonies.

PMID- 29359694
TI  - A Comparative Study: Taxonomic Grouping of Alkaline Protease Producing Bacilli.
AB  - Alkaline proteases have biotechnological importance due to their activity and
      stability at alkaline pH. 56 bacteria, capable of growing under alkaline
      conditions were isolated and their alkaline protease activities were carried out
      at different parameters to determine their optimum alkaline protease production
      conditions. Seven isolates were showed higher alkaline protease production
      capacity than the reference strains. The highest alkaline protease producing
      isolates (103125 U/g), E114 and C265, were identified as Bacillus licheniformis
      with 99.4% and Bacillus mojavensis 99.8% based on 16S rRNA gene sequence
      similarities, respectively. Interestingly, the isolates identified as Bacillus
      safensis were also found to be high alkaline protease producing strains.
      Genotypic characterizations of the isolates were also determined by using a wide
      range of molecular techniques (ARDRA, ITS-PCR, (GTG)5-PCR, BOX-PCR). These
      different techniques allowed us to differentiate the alkaliphilic isolates and
      the results were in concurrence with phylogenetic analyses of the 16S rRNA genes.
      While ITS-PCR provided the highest correlation with 16S rRNA groups, (GTG)5-PCR
      showed the highest differentiation at species and intra-species level. In this
      study, each of the biotechnologically valuable alkaline protease producing
      isolates was grouped into their taxonomic positions with multi-genotypic
      analyses.

PMID- 29359696
TI  - Antimicrobial Effects of Platelet-rich Plasma against Selected Oral and
      Periodontal Pathogens.
AB  - Antimicrobial properties of platelet rich plasma (PRP) against various
      microorganisms have been recently pointed out. PRP could be an alternative to
      conventional antibiotics in preventing oral and periodontal infections. We
      examined whether PRP has in vitro antimicrobial properties against
      Aggregatibacter actinomycetemcomitans, Prophyromonas gingivalis, Staphylococcus
      aureus and Candida albicans. PRP and platelet-poor plasma (PPP) were obtained
      from whole blood of 10 healthy volunteers and 10 periodontitis patients. In vitro
      laboratory susceptibility was carried out using the modified agar diffusion
      method by measuring the diameters of inhibition zones on agar plates coated with
      selected microbial strains. Both calcium chloride (CaCl2) activated and non
      activated samples were tested. Both activated PRP and PPP, of both patients and
      controls, effectively inhibited the growth of A. actinomycetemcomitans, P.
      gingivalis and C. albicans. However, a statistically significant difference in
      favor of PRP was found indicating more susceptibility to PRP than PPP (p < 0.05).
      Non activated PRP and PPP exhibited negative zones of inhibition against the
      studied microorganisms. There was no activity against S. aureus. No statistically
      significant difference was found between the antimicrobial effects of PRP and/or
      PPP obtained from patients and controls (p > 0.05). We conclude that PRP is a
      potentially useful substance against oral and periodontal pathogens. Activated
      PRP was found to be more active than activated PPP and the activation of
      coagulation is a fundamental step. Additionally, the antimicrobial activity of
      PRP and/or PPP seems not to be affected by periodontitis.

PMID- 29359697
TI  - Susceptibility of Vascular Implants to Colonization in vitro by Staphylococcus
      aureus, Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas
      aeruginosa.
AB  - We compared association of Staphylococcus aureus, Staphylococcus epidermidis,
      Pseudomonas aeruginosa and Enterococcus faecalis with nine vascular implants
      after co-culture. Vascular implants were composed of various materials such as
      warp knitted polyester (with or without gelatin and silver ions), expanded
      polytetrafluoroethylene and biological materials - surface treated porcine
      pericardial patch and Omniflow II. The lowest overall number of associated
      bacteria was detected for polytetrafluoroethylene implants and porcine
      pericardial patch. The highest overall number of associated bacteria was detected
      for Omniflow II implant. The major source of variation, i.e. primary factor
      influencing colonization, is the implant type (56.22%), bacterial species is
      responsible for only 1.81%, and interaction of those two factors - 13.09% of
      variation.

PMID- 29359698
TI  - Isolation and Characterization of Phosphate-Solubilizing Bacteria from Mushroom
      Residues and their Effect on Tomato Plant Growth Promotion.
AB  - Phosphorus is a major essential macronutrient for plant growth, and most of the
      phosphorus in soil remains in insoluble form. Highly efficient phosphate
      solubilizing bacteria can be used to increase phosphorus in the plant
      rhizosphere. In this study, 13 isolates were obtained from waste mushroom
      residues, which were composed of cotton seed hulls, corn cob, biogas residues,
      and wood flour. NBRIP solid medium was used for isolation according to the
      dissolved phosphorus halo. Eight isolates produced indole acetic acid (61.5%),
      and six isolates produced siderophores (46.2%). Three highest phosphate
      dissolving bacterial isolates, namely, M01, M04, and M11, were evaluated for
      their beneficial effects on the early growth of tomato plants (Solanum
      lycopersicum L. Wanza 15). Strains M01, M04, and M11 significantly increased the
      shoot dry weight by 30.5%, 32.6%, and 26.2%, and root dry weight by 27.1%, 33.1%,
      and 25.6%, respectively. Based on 16S rRNA gene sequence comparisons and
      phylogenetic positions, strains M01 and M04 belonged to the genus Acinetobacter,
      and strain M11 belonged to the genus Ochrobactrum. The findings suggest that
      waste mushroom residues are a potential resource of plant growth-promoting
      bacteria exhibiting satisfactory phosphate-solubilizing for sustainable
      agriculture.

PMID- 29359699
TI  - Outpatient Antibiotic Consumption Fluctuations in a View of Unreasonable
      Antibacterial Therapy.
AB  - Unreasonable antibacterial therapy is suspected to be the main reason of
      emergence of multi-resistant bacteria. The connection between seasonal
      variability of antibiotic use and reasonable antibacterial therapy has been
      described. We examined the issue basing on the data obtained from the primary
      care system in Szczecin (Poland) in order to verify the situation in this region
      of Central Europe. Increase in antibiotic consumption in a viral infection season
      was proved to be statistically significant. Statistically significant differences
      in various drug forms dispensation were also observed. Increased consumption of
      antibiotics in seasons of influenza-like illnesses might be connected with a lack
      of proper diagnostics or numerous cases of bacterial co-infections.

PMID- 29359700
TI  - Antiviral Resistance of Splenocytes in Aged Mice.
AB  - We compared the susceptibility to viral infection of splenocytes, isolated from
      young versus old CBA mice, and evaluated the antiviral actions of lactoferrin in
      splenocytes infected with Encephalomyocarditis virus (EMCV). Recombinant mouse
      lactoferrin (rmLF) and bovine lactoferrin (bLF) were used. There were no
      differences in the susceptibility to EMCV infection in the studied age
      categories. Both types of lactoferrins were protective in young and old mice. The
      study confirmed the undisturbed viral resistance in old mice and the protective
      actions of lactoferrin in viral infection. The antiviral action of the homologous
      mouse lactoferrin was demonstrated for the first time.

PMID- 29359701
TI  - Deletion of from Streptococcus pyogenes. Results in Hypervirulence in a Mouse
      Model of Sepsis and is LuxS Independent.
AB  - Group A Streptococcus (GAS) is a Gram-positive human pathogen that causes a
      variety of diseases ranging from pharyngitis to life-threatening streptococcal
      toxic shock syndrome. Recently, several global gene expression analyses have
      yielded extensive new information regarding the regulation of genes encoding
      known and putative virulence factors in GAS. A microarray analysis found that
      transcription of the GAS gene M5005_Spy_1343 was significantly increased in
      response to interaction with human polymorphonuclear leukocytes. M5005_Spy_1343
      is predicted to encode a member of the LysR family of transcriptional regulators
      and is located upstream of a putative operon containing six genes. Five of these
      genes have sequence similarity to genes involved in short-chain fatty acid
      metabolism, whereas the sixth gene (luxS) is found in many bacterial species and
      is involved in quorum sensing. Unexpectedly, inactivation of the M5005_Spy_1343
      gene resulted in hypervirulence in an intraperitoneal mouse model of infection.
      Increased virulence was not due to changes in luxS gene expression. We postulate
      that short-chain fatty acid metabolism is involved in GAS pathogenesis.

PMID- 29359702
TI  - Suppressive Effect of Trichoderma spp. on toxigenic Fusarium species.
AB  - The aim of the present study was to examine the abilities of twenty-four isolates
      belonging to ten different Trichoderma species (i.e., Trichoderma atroviride,
      Trichoderma citrinoviride, Trichoderma cremeum, Trichoderma hamatum, Trichoderma
      harzianum, Trichoderma koningiopsis, Trichoderma longibrachiatum, Trichoderma
      longipile, Trichoderma viride and Trichoderma viridescens) to inhibit the
      mycelial growth and mycotoxin production by five Fusarium strains (i.e., Fusarium
      avenaceum, Fusarium cerealis, Fusarium culmorum, Fusarium graminearum and
      Fusarium temperatum). Dual-culture bioassay on potato dextrose agar (PDA) medium
      clearly documented that all of the Trichoderma strains used in the study were
      capable of influencing the mycelial growth of at least four of all five Fusarium
      species on the fourth day after co-inoculation, when there was the first apparent
      physical contact between antagonist and pathogen. The qualitative evaluation of
      the interaction between the colonies after 14 days of co-culturing on PDA medium
      showed that ten Trichoderma strains completely overgrew and sporulated on the
      colony at least one of the tested Fusarium species. Whereas, the microscopic
      assay provided evidence that only T. atroviride AN240 and T. viride AN255 formed
      dense coils around the hyphae of the pathogen from where penetration took place.
      Of all screened Trichoderma strains, T. atroviride AN240 was also found to be the
      most efficient (69-100% toxin reduction) suppressors of mycotoxins
      (deoxynivalenol, 3-acetyl-deoxynivalenol, 15-acetyl-deoxynivalenol, nivalenol,
      zearalenone, beauvericin, moniliformin) production by all five Fusarium species
      on solid substrates. This research suggests that T. atroviride AN240 can be a
      promising candidate for the biological control of toxigenic Fusarium species.

PMID- 29359703
TI  - Charge and orbital orders and structural instability in high-pressure quadruple
      perovskite CeCuMn6O12.
AB  - We prepared a quadruple perovskite CeCuMn6O12 under high-pressure and high
      temperature conditions at 6 GPa and about 1670 K and investigated its structural,
      magnetic and transport properties. CeCuMn6O12 crystallizes in space group Im-3
      above T CO  =  297 K; below this temperature, it adopts space group R-3 with the
      1:3 (Mn4+:Mn3+) charge and orbital orders. Unusual compressed Mn3+O6 octahedra
      are realized in CeCuMn6O12 similar to CaMn7O12 with the  -Q 3 Jahn-Teller
      distortion mode. Below about 90 K, structural instability takes place with phase
      separation and the appearance of competing phases; and below 70 K, two R-3 phases
      coexist. CeCuMn6O12 exhibits a ferromagnetic-like transition below T C  =  140 K,
      and it is a semiconductor with the magnetoresistance reaching about  -40% at 140
      K and 70 kOe. We argued that the valence of Ce is  +3 in CeCuMn6O12 with the
      Ce3+([Formula: see text])([Formula: see text])O12 charge distribution in the
      charge-ordered R-3 phase and Ce3+([Formula: see text])([Formula: see text])O12 in
      the charge-disordered Im-3 phase.

PMID- 29359704
TI  - Biomaterials for revascularization and immunomodulation after spinal cord injury.
AB  - Spinal cord injury (SCI) causes immediate damage to the nervous tissue
      accompanied by loss of motor and sensory function. The limited self-repair
      competence of injured nervous tissue underscores the need for reparative
      interventions to recover function after SCI. The vasculature of the spinal cord
      plays a crucial role in SCI and repair. Ruptured and sheared blood vessels in the
      injury epicenter and blood vessels with a breached blood-spinal cord barrier
      (BSCB) in the surrounding tissue cause bleeding and inflammation, which
      contribute to the overall tissue damage. The insufficient formation of new
      functional vasculature in and near the injury impedes endogenous tissue repair
      and limits the prospect of repair approaches. Limiting the loss of blood vessels,
      stabilizing the BSCB, and promoting the formation of new blood vessels are
      therapeutic targets for spinal cord repair. Inflammation is an integral part of
      injury-mediated vascular damage, which has deleterious and reparative
      consequences. Inflammation and the formation of new blood vessels are intricately
      interwoven. Biomaterials can be effectively used for promoting and guiding blood
      vessel formation or modulating the inflammatory response after SCI, thereby
      governing the extent of damage and the success of reparative interventions. This
      review deals with the vasculature after SCI, the reciprocal interactions between
      inflammation and blood vessel formation, and the potential of biomaterials to
      support revascularization and immunomodulation in damaged spinal cord nervous
      tissue.

PMID- 29359705
TI  - A dual caudal-fin miniature robotic fish with an integrated oscillation and jet
      propulsive mechanism.
AB  - This paper presents the development of a biomimetic robotic fish that uses an
      integrated oscillation and jet propulsive mechanism to enable good swimming
      performance for small robotic fish. The designed robotic fish is driven by two
      caudal fins that flap oppositely, which are equipped in parallel at the fish
      tail. The propulsive mechanism of dual caudal fins is characterized by using
      numerical analysis, in which the distance between the two caudal fins is a key
      factor to the integrated mechanism and plays an important role to swimming
      performance. This finding has been further verified by experiments performed on a
      miniature robotic fish prototype with 100 mm length and 30 mm diameter.
      Experimental results have demonstrated the influence of the distance between the
      two caudal fins to swimming performance. The designed miniature robotic fish can
      swim stably and efficiently while exhibiting good motion maneuverability such as
      turning and braking. The developed robotic fish, with advantages of excellent
      swimming performance and small size, can be potentially used for monitoring and
      exploration in the underwater environment.

PMID- 29359706
TI  - Refining non-invasive techniques to measure intracranial pressure: comparing
      evoked and spontaneous tympanic membrane displacements.
AB  - OBJECTIVE: Tympanic membrane displacements (TMDs) are used to non-invasively
      gauge inner-ear fluid pressure. Inner-ear fluid pressure equalizes with
      intracranial pressure (ICP) via the cochlear aqueduct and therefore TMDs can
      indirectly evaluate ICP. We studied the relationship between two TMD modalities,
      evoked and spontaneous. Evoked TMD is a reflex response to an auditory stimulus
      and the established stapes-footplate mechanism explains how evoked TMDs change
      with ICP. Spontaneous TMD refers to a pulsatile TMD waveform expressed in the
      form of pulse amplitudes (TMD-PAs), the origins of which are poorly understood.
      We investigated whether both modalities respond similarly to an ICP change,
      suggesting a common mechanism. APPROACH: ICP was manipulated in 20 healthy
      volunteers by a postural change from sitting (lower ICP) to supine (higher ICP).
      Differences between paired sitting and supine TMD results generated DeltaEvoked
      and DeltaSpontaneous values. MAIN RESULTS: Evoked TMDs became more inward on
      lying supine while spontaneous TMDs became more outward. There was no evidence of
      a correlation between DeltaEvoked and DeltaSpontaneous (Right ears: r  =  -0.38,
      p  =  0.10, 95% CI  -0.75 to 0.21; Left ears: r  =  0.34, p  =  0.16, 95% CI  
      0.17 to 0.75). SIGNIFICANCE: This suggests the stapes-footplate mechanism is not
      the primary mechanism explaining how spontaneous TMDs respond to changing ICP.

PMID- 29359707
TI  - Comparison of surface structures of corundum Cr2O3(0 0 0 1) and V2O3(0 0 0 1)
      ultrathin films by x-ray photoelectron diffraction.
AB  - Thin Cr2O3(0 0 0 1) layers are formed by oxidation of a Cr(1 1 0) single crystal.
      This surface is further modified by growing an epitaxial ultrathin V2O3(0 0 0 1)
      film by reactive vapor deposition. Synchrotron based soft-x-ray photoemission
      spectroscopy and x-ray photoelectron diffraction are used to characterize the
      surface layers of these two corundum-structured oxides. By comparison of
      experimental XPD patterns with simulated electron multiple scattering
      calculations, two distinctively different surface terminations are extracted for
      the two oxides. While for V2O3 we confirm the previously proposed vanadyl
      terminated surface structure, we propose a new surface structure for Cr2O3 that
      consists of excess chromium atoms occupying interstitial sub-surface sites.

PMID- 29359708
TI  - Devising tissue ingrowth metrics: a contribution to the computational
      characterization of engineered soft tissue healing.
AB  - The paradigm shift brought about by the expansion of tissue engineering and
      regenerative medicine away from the use of biomaterials, currently questions the
      value of histopathologic methods in the evaluation of biological changes. To
      date, the available tools of evaluation are not fully consistent and satisfactory
      for these advanced therapies. We have developed a new, simple and inexpensive
      quantitative digital approach that provides key metrics for structural and
      compositional characterization of the regenerated tissues. For example, metrics
      provide the tissue ingrowth rate (TIR) which integrates two separate indicators;
      the cell ingrowth rate (CIR) and the total collagen content (TCC) as featured in
      the equation, TIR% = CIR% + TCC%. Moreover a subset of quantitative indicators
      describing the directional organization of the collagen (relating structure and
      mechanical function of tissues), the ratio of collagen I to collagen III
      (remodeling quality) and the optical anisotropy property of the collagen
      (maturity indicator) was automatically assessed as well. Using an image analyzer,
      all metrics were extracted from only two serial sections stained with either
      Feulgen & Rossenbeck (cell specific) or Picrosirius Red F3BA (collagen specific).
      To validate this new procedure, three-dimensional (3D) scaffolds were
      intraperitoneally implanted in healthy and in diabetic rats. It was hypothesized
      that quantitatively, the healing tissue would be significantly delayed and of
      poor quality in diabetic rats in comparison to healthy rats. In addition, a
      chemically modified 3D scaffold was similarly implanted in a third group of
      healthy rats with the assumption that modulation of the ingrown tissue would be
      quantitatively present in comparison to the 3D scaffold-healthy group. After 21
      days of implantation, both hypotheses were verified by use of this novel
      computerized approach. When the two methods were run in parallel, the
      quantitative results revealed fine details and differences not detected by the
      semi-quantitative assessment, demonstrating the importance of quantitative
      analysis in the performance evaluation of soft tissue healing. This automated and
      supervised method reduced operator dependency and proved to be simple, sensitive,
      cost-effective and time-effective. It supports objective therapeutic comparisons
      and helps to elucidate regeneration and the dynamics of a functional tissue.

PMID- 29359709
TI  - Field-induced magnetic phase transitions and memory effect in bilayer ruthenate
      Ca3Ru2O7 with Fe substitution.
AB  - Bilayer ruthenate Ca3(Ru1-x Fe x )2O7 (x  =  0.05) exhibits an incommensurate
      magnetic soliton lattice driven by the Dzyaloshinskii-Moriya interaction. Here we
      report complex field-induced magnetic phase transitions and memory effect in this
      system via single-crystal neutron diffraction and magnetotransport measurements.
      We observe first-order incommensurate-to-commensurate magnetic transitions upon
      applying the magnetic field both along and perpendicular to the propagation axis
      of the incommensurate spin structure. Furthermore, we find that the metastable
      states formed upon decreasing the magnetic field depend on the temperature and
      the applied field orientation. We suggest that the observed field-induced
      metastability may be ascribable to the quenched kinetics at low temperature.

PMID- 29359710
TI  - Initial organ distribution and biological safety of Mg2+ released from a Mg alloy
      implant.
AB  - Magnesium (Mg) alloys are considered promising materials for biodegradable
      medical devices; however, the initial effects and distribution of released Mg2+
      ions following implantation are unclear. This is addressed in the present study,
      using two types of Mg alloys implanted into rats. An in vitro immersion test was
      first carried out to quantify Mg2+ ions released from the alloys at early stages.
      Based on these data, we performed an in vivo experiment in which large amounts of
      alloys were subcutaneously implanted into the backs of rats for 1, 5, 10, and 25
      h. Mg2+ accumulation in organs was measured by inductively coupled plasma mass
      spectrometry. In vivo, blood and urine Mg2+ concentrations were higher in rats
      receiving the implants than in controls after 1 h; however, the levels were
      within clinically accepted guidelines. The Mg2+ concentration in bone was
      significantly higher in the 25 h implanted group than in the other groups. Our
      results suggest that homeostasis is maintained by urinary excretion and bone
      accumulation of released Mg2+ ions in response to sudden changes in Mg2+ ion
      concentration in the body fluid in a large number of Mg alloy implants at the
      early stages.

PMID- 29359712
TI  - Zinc Oxide Decorated Multiwalled Carbon Nanotubes: Their Bolometric Properties.
AB  - We report the synthesis of MWNTs/ZnO hybrid nanostructures. A simple, affordable,
      chemical procedure to functionalize MWNT with ZnO nanoparticles was performed. A
      significant portion of the surface of MWNTs is covered with ZnO nanoparticles,
      such particles form highly porous spherical nodules of 50-150 nm in diameter,
      sizes that are in values one order of magnitude larger than similar ZnO
      nanonodules reported in the literature. Hence, in the self-assembled
      nanocomposite the ZnO exhibits a large surface to volume ratio, which is a very
      advantageous property for potential catalytic applications. The resultant
      MWNTs/ZnO nanocomposites were characterized by X-ray diffraction, scanning and
      high-resolution transmission electron microscopy, and UV-Vis and Raman
      spectroscopies. The temperature coefficient of resistance (TCR) of the
      nanocomposites was measured and reported. The average TCR value goes from 
      5.6%/K, and up to -18%/K, on temperature change intervals from 10 K to 1 K,
      respectively. Based on TCR results, the nanocomposite MWNTs/ZnO prepared in this
      work is a promising material with potential application as a bolometric sensor.

PMID- 29359713
TI  - Low-cost synthesis of pure ZnO nanowalls showing three-fold symmetry.
AB  - ZnO nanowalls (NWLs) represent a non-toxic, Earth abundant, high surface-to
      volume ratio, semiconducting nanostructure which has already showed potential
      applications in biosensing, environmental monitoring and energy. Low-cost
      synthesis of these nanostructures is extremely appealing for large scale
      upgrading of laboratory results, and its implementation has to be tested at the
      nanoscale, at least in terms of chemical purity and crystallographic orientation.
      Here, we have produced pure and texturized ZnO NWLs by using chemical bath
      deposition (CBD) synthesis followed by a thermal treatment at 300  degrees C. We
      examined the NWL formation process and the new obtained structure at the
      nanoscale, by means of scanning and transmission electron microscopy in
      combination with x-ray diffraction and Rutherford backscattering spectrometry. We
      have shown that only after annealing at 300  degrees C in nitrogen does the as
      grown material, composed of a mixture of Zn compounds NWLs, show its peculiar
      crystal arrangement. The resulting ZnO sheets are in fact made by ZnO wurtzite
      domains (4-5 nm) that show a particular kind of texturization; indeed, they are
      aligned with their own c-axis always perpendicular to the sheets forming the wall
      and rotated (around the c-axis) by multiples of 20 degrees  from each other. The
      presented data show that low-cost CBD, followed by an annealing process, gives
      pure ZnO with a peculiarly ordered nanostructure that shows three-fold symmetry.
      Such evidence at the nanoscale will have significant implications for realizing
      sensing or catalyst devices based on ZnO NWLs.

PMID- 29359711
TI  - Real-time detection and discrimination of visual perception using
      electrocorticographic signals.
AB  - OBJECTIVE: Several neuroimaging studies have demonstrated that the ventral
      temporal cortex contains specialized regions that process visual stimuli. This
      study investigated the spatial and temporal dynamics of electrocorticographic
      (ECoG) responses to different types and colors of visual stimulation that were
      presented to four human participants, and demonstrated a real-time decoder that
      detects and discriminates responses to untrained natural images. APPROACH: ECoG
      signals from the participants were recorded while they were shown colored and
      greyscale versions of seven types of visual stimuli (images of faces, objects,
      bodies, line drawings, digits, and kanji and hiragana characters), resulting in
      14 classes for discrimination (experiment I). Additionally, a real-time system
      asynchronously classified ECoG responses to faces, kanji and black screens
      presented via a monitor (experiment II), or to natural scenes (i.e. the face of
      an experimenter, natural images of faces and kanji, and a mirror) (experiment
      III). Outcome measures in all experiments included the discrimination performance
      across types based on broadband gamma activity. MAIN RESULTS: Experiment I
      demonstrated an offline classification accuracy of 72.9% when discriminating
      among the seven types (without color separation). Further discrimination of grey
      versus colored images reached an accuracy of 67.1%. Discriminating all colors and
      types (14 classes) yielded an accuracy of 52.1%. In experiment II and III, the
      real-time decoder correctly detected 73.7% responses to face, kanji and black
      computer stimuli and 74.8% responses to presented natural scenes. SIGNIFICANCE:
      Seven different types and their color information (either grey or color) could be
      detected and discriminated using broadband gamma activity. Discrimination
      performance maximized for combined spatial-temporal information. The
      discrimination of stimulus color information provided the first ECoG-based
      evidence for color-related population-level cortical broadband gamma responses in
      humans. Stimulus categories can be detected by their ECoG responses in real time
      within 500 ms with respect to stimulus onset.

PMID- 29359714
TI  - [Children and adolescents in situations of social distress].
AB  - The review article addresses transnational problems of socially stressful events
      and their contribution to the mental state of children and adolescents. The
      authors suggest the concept of distorted socialization in minors, who had
      experienced adverse events, with the formation of the concept of socially
      maladaptive distress reactions (SMDR). This typology has not just the age-related
      dynamics but also the gender specificity. Research methodology and systemic
      approach to SMDR from the perspective of understanding by specialists of various
      professions are significant for psychologists, neurologists and children's and
      adolescents' psychiatrists, including the forensic-psychiatric experts. The
      combined approach is important for the diagnostic qualification of conditions,
      development of correctional psychotherapeutic programs and expert approaches with
      reliance on gender signs, qualitative and quantitative characteristics of
      personal response in identifying SMDR.

PMID- 29359715
TI  - [Clinical and neuroimaging signs of cardioembolic stroke in children].
AB  - AIM: To study clinical and neuroimaging signs of cardioembolic stroke (CES) in
      children. MATERIAL AND METHODS: A group of 100 patients with arterial ischemic
      stroke (AIS), aged from 1 month to 15 years, was stratified into the main group
      (10 patients with CES) and the comparison group (90 patients with other subtypes
      of AIS). CT and MRI, MR-angiography, ultrasound study as well as assessment of
      clinical symptoms on PedNIHSS were performed. The duration of follow-up was from
      2 month to 14 years. The follow-up allowed the assessment of occurrence of
      secondary strokes, severity of residual neurological symptoms on the PSOM and
      fatal outcomes. Special attention was drawn to the use of CASSADE criteria for
      CES. RESULTS AND CONCLUSION: Clinical features that help to diagnose CES, even in
      the absence of adequate neuroimaging, in patients with heart disease, which is a
      potential high risk factor for cardioembolia, were established. These factors
      include early disease onset, acute development and progression of neurological
      deficit to the maximal level in the first 5 min., marked severity of the acute
      period (PedNIHSS > 15), early recovery of neurological functions, significant
      residual neurological symptoms (PSOM > 2). These symptoms should be used in
      addition to the CASCADE criteria in the diagnosis of CES of AIS type in children.

PMID- 29359716
TI  - [Epileptic syndromes in childhood associated with secondary generalized tonic
      clonic seizures].
AB  - AIM: To study a group of patients with secondary generalized tonic-clonic
      seizures (SGTCS) in view of nosology, medical history, clinical,
      electroencephalographic and neuroimaging features. MATERIAL AND METHODS: The
      study included 471 patients, 244 (51.8%) men and 227 (48.2%) women. RESULTS:
      SGTCS were observed in many epileptic syndromes. The most frequent were
      symptomatic focal epilepsy (33.8%), cryptogenic focal epilepsy (23.8%), rolandic
      epilepsy (12.6%), FEBL-BEDC syndrome (12.3%). Other forms of epilepsy were less
      frequent. The onset of epilepsy ranged over a wide age range from the first month
      of life to 18 years. The average age of onset was 5.7+/-4.96 years. SGTCS as the
      only type of paroxysms were observed in 28.3% of cases. Two or more types of
      seizures were observed in 71.7% of patients, three or more types in 39.3%.
      Epileptiform activity on EEG during long VEM was detected in 91.3% of patients
      with SGTCS. In 37.2% of patients, benign epileptiform discharges of childhood
      were recorded. Treatment with antiepileptic drugs (AEP) led to complete remission
      in 57.1% of cases of epilepsy associated with SGTCS. A reduction of the frequency
      of seizures by 50% or more was found in 33.6% of patients treated with AEP. No
      effect was observed in 9.3% of patients. CONCLUSION: Significant differences in
      the prognosis and therapeutic approaches to specific epileptic syndromes
      associated with SGTCS necessitate the use of the entire spectrum of diagnostic
      measures, which should include careful history taking, clinical examination,
      video-EEG monitoring with the inclusion of sleep dynamics, MRI / CT brain,
      genetic testing.

PMID- 29359717
TI  - [Neuropsychological evaluation of children in low conciseness state after a
      severe traumatic brain injury].
AB  - AIM: To follow up patterns of cognitive recovery in children (6-17 years of age)
      at the first four months after a severe traumatic brain injury (TBI). MATERIAL
      AND METHODS: Seventeen children with TBI (GCS <=8) were evaluated with the Coma
      Recovery Scale-R (CRS). Children were stratified into three groups according to
      their consciousness recovery. Seven children regained their consciousness
      completely and were assessed by the Luria Neuropsychological Battery test. Six
      children remained in the minimally conscious state (MCS) and were tested by the
      adapted procedure of neuropsychological assessment during the first four months.
      Four children with low level of consciousness were evaluated with CRS. RESULTS
      AND CONCLUSION: The most destroying functions at the early recovery period were
      the processing speed (neurodynamics of mental activity), executive functions and
      memory. Children with the anterior cortex damage had the slowest dynamics of
      recovery. The slower dynamics of consciousness recovery was combined with severe
      primary damages of visual gnosis, speech and executive functions according to
      neuropsychological examination. The positive dynamics of consciousness recovery
      was combined with early behavioral changes and the greater rate of behavioral
      changes.

PMID- 29359718
TI  - [Neurological disorders in preterm children with neuropathy].
AB  - AIM: To establish the correlation between the frequency and severity of hypoxic
      CNS lesions in preterm children with neuropathy and improve the early diagnosis
      of lesions of the brain structures based on clinical ophthalmologic results.
      MATERIAL AND METHODS: The authors examined 712 premature infants with body mass
      <1500 g born before 30 weeks of gestation during 2006-2016. Ophthalmological
      monitoring of retinopathy (RP), an analysis of medical history, neurological
      examination and neurosonography were performed. RESULTS AND CONCLUSION: RP was
      found in 367 (51.5%) children. In 255 children, the disease regressed naturally.
      One hundred and twelve (15.7%) children, underwent laser coagulation of the
      avascular retina due to the severity of RP. Signs of intraventricular hemorrhages
      (IVH) were noted in 434 (61%) children in the neonatal period. IVH were found in
      285 (77.6%) children with RP. RP with the regression after laser coagulation was
      combined with IVH in 98% of cases, with the higher frequency (55.3%) of IVH, 3rd
      degree. Periventricular leucomalation (PVL) was found in 10% of children without
      RP, in 22.3% of children with RP with naturally regression and in 51,7% of
      children with RP with laser coagulation of the retina. In 70 children,
      neurosonographic signs of ischemia of the head of caudate nucleus were identified
      on the 14-15th days of life. In this group, RP developed in 54 (77%) children, 27
      (38.5%) children needed laser coagulation of the retina. The correlation found
      between the severity of RP and hypoxic CNS lesions in highly preterm infants
      might allow the prognosis of visual and neurosomatic disturbances in the early
      age and timely effective rehabilitation.

PMID- 29359719
TI  - [Pediatric acute-onset neuropsychiatric syndrome: clinical/laboratory
      characteristics].
AB  - AIM: Based on the current conceptions on the genesis of hyperkinetic syndromes in
      children and adolescents, to single out a group of patients with suggestive PANS,
      compare clinical and laboratory results and determine clinical/laboratory
      characteristics of this syndrome. MATERIAL AND METHODS: Sixty-nine patients with
      tics were studied using neurological examination, questionnaires and
      international scales for assessment of tics, obsessive-compulsive disorders and
      attention deficit hyperactivity disorder (ADHD). Laboratory tests included
      general blood tests, antistreptolysin O test, determination of rheumatoid factor,
      C-reactive protein, circulating immune complexes, nasopharyngeal wash for beta
      hemolytic streptococcus, antineuronal antibodies and immunoglobulins A, M, G, E,
      CD4, CD8-lymphocytes. The same tests were performed in the control group. RESULTS
      AND CONCLUSION: Clinical symptoms were different by the severity and
      phenomenology of tic hyperkineses in patients with PANS compared to the patients
      with tics without immune disorders. Most of the patients were diagnosed with
      Tourette syndrome. ADHD was the most common diagnosis in the PANS group. Its
      frequency was 2.5 higher in the male patients. A chronic focus of infection did
      no predict the development of PANS. Based on the laboratory results, one can
      assume that beta-hemolytic streptococcus A infection, lower JgM levels and an
      elevated CD8+ lymphocytes predict the development of autoimmune mental and
      neurological disorders in the group of PANS patients.

PMID- 29359720
TI  - [The course and the development of epilepsy in patients with typical variant of
      Rett syndrome and mutations].
AB  - AIM: Studying data of anamnesis, clinical state, electro-encephalographic, brain
      MRI in patients with Rett syndrome (MESR2). MATERIAL AND METHODS: We studied 11
      patients (female) from three to 23 years old with Rett syndrome and MeCP2
      mutations. Observation continued 10 years (2006-2015). We analyzed the results of
      the neurological status, night sleep video-EEG monitoring, MRI. RESULTS AND
      CONCLUSION: Epilepsy diagnosed in six cases (54, 5%). The overage age of debut of
      epileptic seizures was 3 years 9 months. There are some types of seizures:
      generalized, myoclonic, myotonic, tonic, versive, focal motor, atypical absences.
      Status epilepticus evolved in one patient. Generalized seizures were 56, 25%,
      focal seizures - 43, 75%. EEG changing marked in nine patients (81, 8%): slowdown
      back activity, episodes of periodic regional slowdown, regional epileptiform
      activity, and diffuse epileptiform activity like benign focal epileptiform
      discharges (BFED). five patients took antiepileptic drugs. All of them had
      improved during treatment. There were reducing of frequency of the seizures up
      50% - 4 cases (80%). one patients with resistant epilepsy was taken combination
      of drugs (levetirecetam, topiromat, zonisamide, benzodiazepine) with stopping of
      seizures in the night sleep and decreasing of frequency of daytime seizures to
      50%. We believe there is very important of study epilepsy in patients with Rett
      syndrome and improvement of its treatment.

PMID- 29359721
TI  - [Niemann-Pick type C disease in a child].
AB  - The authors consider a clinical case of Niemann-Pick disease type C, an orphan
      hereditary autosomal recessive neurodegenerative disease belonging to the group
      of lysosomal storage disease, in an 11-year female patient with the late
      infantile form of the disease. The combination of psychomotor retardation,
      polymorphic neurological symptoms and physical changes in the form of isolated
      splenomegaly suggested the diagnosis of Niemann-Pick type C disease. DNA testing
      was carried out using direct automated sequencing. The patient was treated with
      miglustat.

PMID- 29359722
TI  - [Cytoflavin efficacy in the treatment of disseminated encephalomyelitis in
      children].
AB  - AIM: To evaluate the efficacy of cytoflavin in the complex therapy of
      disseminated encephalomyelitis in children. MATERIAL AND METHODS: A blind,
      placebo - controlled, randomized study was carried out. Thirty-two patients, aged
      form 1 to 17 years, received cytoflavin from the first day after admission in
      intravenous drips in 5% glucose solution during 10 days. The control group
      consisted of 30 children who received a standard infusion therapy. Clinical and
      laboratory evaluation was carried out on the 11th and 30th days, MRT was
      performed before hospitalization and on the 30th day. RESULTS AND CONCLUSION:
      Cytoflavin had a positive effect on the rate of recovery of the majority of
      neurological symptoms. The average EDSS score decreased by 1.5 times to the 30th
      day compared with the control group. The complete regression of clinical symptoms
      and focal changes on MRI on the 30th day was observed in 25% of children of the
      main group and in 3.3% in the control group (r=0.001). The drug exerted the
      endothelium protective and antioxidant effects, improved blood rheology and
      restored the content of circulating endothelial cells, the level of D-dimer and
      indicators of free radical oxidation to the 30th day of treatment.

PMID- 29359723
TI  - [A strategy for increasing the efficiency of psychopharmacological treatment of
      hyperkinetic behavior disorder with pantogam].
AB  - AIM: To assess short-term efficiency of hopantenic acid (pantogam) in the
      treatment of children with hyperkinetic behavior disorder, in whom the previous
      treatment with atomoxetine was not efficient. MATERIAL AND METHODS: Twenty-four
      children (16 boys and 8 girls), aged 6-11 years, diagnosed with hyperkinetic
      behavior disorder (ICD-10 item F90.1) were enrolled in this open non-randomized
      study. RESULTS AND CONCLUSION: A short-term positive therapeutic dynamics was
      observed when introducing hopantenic acid (pantogam) augmentation strategy to
      existing atomoxetine therapy. Qualitative improvements in children's state were
      found not only in the ability to control symptoms but also in their social
      functioning levels and quality of life. The proposed therapeutic strategy can
      help to improve treatment outcomes for children with certain clinical forms of
      hyperkinetic behavior disorder.

PMID- 29359724
TI  - [Treatment of speech disorders in preschool children].
AB  - AIM: To study the efficacy of neyroferon in developmental speech disorders (SDD).
      MATERIAL AND METHODS: Thirty preschool children were stratified into 3 groups: 4
      5 years (n=8), 5-6 years (n=10) and 6-7 years (n=12). The children were treated
      with neyroferon in dose 1 tablet three times a day during 2 month. A multifaceted
      study of speech disorders using several methods was conducted. General mental
      state, emotional and behavioral characteristics of the children were assessed as
      well. RESULTS AND CONCLUSION: A therapeutic effect of neyroferon (the improvement
      of auditory-speech memory, expressive speech, phonemic perception, articulatory
      movements, vocabulary activity, connected speech etc) as well as the decrease in
      anxiety, hyperactivity and attention deficit was found in children with SDD. The
      safety of the drug was confirmed. The results should be treated as preliminary
      ones.

PMID- 29359725
TI  - [Monoamine metabolism in children with hyperkinetic disorder].
AB  - In this review article, the authors consider a role of interaction between
      noradrenergic and dopaminergic systems in children with hyperkinetic disorder
      without impairment of the operational system of intelligence. The uneven
      development of higher mental functions observed in these cases is determined by
      the specificity of the formation of functional systems and the inclusion of
      compensatory mechanisms as well.

PMID- 29359726
TI  - [Sleep quality and its parameters in schoolchildren].
AB  - AIM: Sleep disorders are very common among teenagers. One of possible reasons is
      a discrepancy between social and biological activity of children. It is known
      that adolescents with a late chronotype (e.g., a later midpoint of sleep) have a
      lowered academic achievement. The aim of our study was to evaluate sleep quality
      and other sleep-wake characteristics in relation to academic scores self-reported
      by teenagers living in urban and rural areas of Republic of Karelia. MATERIAL AND
      METHODS: Five hundred respondents, aged 10-17 years, participated in a
      questionnaire survey of chronotype and sleep quality. The Munich chronotype
      questionnaire (MCTQ) and the Pittsburgh Sleep Quality Index (PSQI) were used.
      Sleep duration during week and weekend, sleep quality and hygiene were assessed.
      RESULTS AND CONCLUSION: A decrease in sleep duration in adolescents, aged 10-18
      years, was observed. A larger social jetlag was significantly higher in girls
      compared to boys. Gender had a significant impact on sleep quality. More than 10%
      of the total variation in academic achievement of Karelian teenagers can be
      explained by the difference in their gender and average sleep duration.

PMID- 29359728
TI  - [Gut human microbiota and multiple sclerosis].
AB  - Recently the relationship between gut microbiota changes and the development of
      immune-mediated diseases of the central nervous system (CNS) has been reported.
      This review presents literature data on the effect of gut microbiota on the
      function of the immune and nervous systems. The authors discuss possible
      mechanisms of the relationship between gut microbiota changes and CNS diseases on
      the model of multiple sclerosis (MS).

PMID- 29359727
TI  - [The association of intrathecal production of immunoglobulin free light chains
      and progression of multiple sclerosis].
AB  - AIM: To assess an impact of immunoglobulin free light chains (FLC) on short-term
      and long-term prognosis of clinical and radiological activity and progression of
      disability in multiple sclerosis (MS). MATERIAL AND METHODS: A sample of 381
      patients with definite MS was divided into 2 groups. In group 1, lumbar puncture
      was performed at the time of clinically isolated syndrome, and patients were
      prospectively followed up to 2 years (short-term prognosis group, n=97). In group
      2, MS was diagnosed immediately after lumbar puncture, and retrospective analysis
      of the disease course with the duration not less than 5 years was performed (long
      term prognosis group, n=284). The Expanded Disability Status Scale (EDSS) and the
      Multiple Sclerosis Severity Score (MSSS) were used to assess patient's status.
      Concentrations of kappa and lambda FLC in the CSF (K-FLCCSF, L-FLCCSF) and serum
      (K-FLCSERUM, L-FLCSERUM) as well as quotients of concentrations (Q-K and Q-L)
      were determined. Patients were stratified into subgroups with high and low
      concentrations of K-FLC and L-FLC using cut-offs from our previous studies: K
      FLCCSF=0.595 mcg/l and L-FLCCSF=0.127 mcg/l. RESULTS: In group 1, significant
      correlations were found only between EDSS score and concentrations of K-FLCCSF
      (r=0.377, p=0.00019) and Q-K (r=0.366, p=0.0012). FLC concentrations did not
      correlate with the number of relapses and new T2 lesions. The age and EDSS score
      at the disease onset didn't differ between patients with high and low K-FLC and L
      FLC (K-FLCCSF: r=0.2658; L-FLCCSF: r=0.5502). A significant decrease of EDSS
      score after the disease onset was observed in all groups except for patients with
      high concentrations of K-FLCCSF (p=0.1844), so the EDSS score after 2 years was
      significantly higher in this subgroup of patients (p=0.0006). In group 2,
      significant correlations of K-FLC with EDSS score (r=0.181, p=0.002) and MSSS
      score (r=0.121, r=0.044) for long-term prognosis (median (IQR) = 8 (6-13) years)
      were found. No correlations of FLC concentrations with the number of relapses
      during the first 5 years were found. Survival analysis showed that high
      concentrations of K-FLCCSF were associated with the high risk of progression to
      EDSS 6 (HR=2.055, p=0.026) but not with EDSS 4 (HR=2.388, p=0.08). CONCLUSION:
      Concentrations of kappa FLC can help to define the prognosis of MS early at the
      disease course. Although low concentrations of FLC do not exclude a severe
      disease phenotype, patients with high K-FLCCSF concentrations are at greater risk
      for faster MS progression, probably, due to impaired reparation of neural tissue.
      Measurement of FLC concentrations can be used to determine a therapeutic tactics
      in patients with MS.

PMID- 29359729
TI  - [Area postrema lesion as a cause of intractable nausea, vomiting and hiccups in
      neuromyelitis optica spectrum disorders].
AB  - Neuromyelitis optica (Devic's disease) is a chronic autoimmune disease associated
      with the production of anti-bodies to aquaporin-4 (AQP4). Area postrema lesions
      is the third, after optic neuritis and myelitis, syndrome of opticomyelitis
      related disorders. Clinical symptoms of this disorder include intractable nausea,
      vomiting and hiccups. In many cases, area postrema syndrome manifests as the
      first clinical symptom of a neuromyelitis optica spectrum disorder that hampers
      the diagnosis. The authors present a case report of a female patient with area
      postrema lesions developed several months before the first disabling attack of
      myelitis.

PMID- 29359730
TI  - [Syndrome CLIPPERS (literature review and a case report)].
AB  - This paper presents a brief literature review on chronic lymphocytic inflammation
      with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome.
      Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome as
      well as treatment approaches are discussed. The authors present a case of a 56
      year old patient with CLIPPERS syndrome in West Siberia.

PMID- 29359731
TI  - [Primary progressive multiple sclerosis: current issues of timely diagnosis].
AB  - This article presents a review of international data on primary progressive
      multiple sclerosis (PPMS) and an analysis of factors influencing timely diagnosis
      of PPMS in a number of regions of the Russian Federation.

PMID- 29359732
TI  - [The efficacy of the exoskeleton ExoAtlet to restore walking in patients with
      multiple sclerosis].
AB  - AIM: To investigate the efficacy and safety of the exoskeleton ExoAtlet in
      complex therapy of patients with multiple sclerosis (MS). MATERIAL AND METHODS: A
      pilot study within the prospective open controlled program was conducted.
      Eighteen patients with relapsing-remitting MS (RRMS) in remission and secondary
      progressive MS (SPMS) with the level of neurological deficit on the EDSS from 3
      to 7 points have completed the study. EDSS, MSFC, HADS, MoCA scales were
      administered and the force measuring insoles F-Scan Tekscan (USA) were used to
      study the biomechanics of walking. RESULTS AND CONCLUSION: Good tolerability of
      workload within 30-40 min. was observed. The improvement in the EDSS was detected
      in 9 patients, in whole, a significant positive trend (p<0.01) was shown. The
      study of the biomechanics of the walk showed its significant impairment compared
      to healthy individuals: reduction of parameters of rate, speed and step length,
      significant instability, pronounced asymmetry, the decrease in support and shock
      lower limb function, high coefficient of variability of the parameters, the
      phenomenon of recurrence of the vertical component of support reactions. After a
      course of exercise of walking in the exoskeleton, the walking speed and stability
      increased, oscillation of the body decreased, support function increased, the
      phenomenon of cyclical changes of the vertical component of support reactions
      reduced. The results of the pilot study showed promising future research
      opportunities for robotic-assisted walking and maintenance of the vertical
      posture with the help of the exoskeleton ExoAtlet to restore the abilities of
      movement in MS patients with locomotor disorders.

PMID- 29359733
TI  - [The search for optimal decision in the treatment of multiple sclerosis: to
      improve adherence not reducing the efficacy].
AB  - Long-term disease modifying therapy (DMD) therapy is the basis of modern MS
      treatment, effiecacy of which is modulated by the patient's adherence to therapy.
      One of the possible solutions of low adherence improvement is the use of
      innovative drugs and the development of more convenient regimens of injectable
      medications. This article gives a brief review of peg-interferon beta-1a clinical
      trials.

PMID- 29359734
TI  - [An analysis of clinical trials on the registration of similars of the original
      disease-modifying therapies].
AB  - The article discusses the design and results of recently published study of an
      analog of the original glatiramer acetate. The necessity of the correct planning
      and analysis of the data of such studies is stressed, showing equal efficacy,
      tolerability and safety of analog and original drug. The optimal design of such
      studies, their duration, selection of primary endpoint, adequate assessment of
      clinical and MRI changes and side-effects are discussed. The authors reckon that
      it is impossible to plan studies the results of which are based on the design,
      i.e. the absence of differences from the original drug. The authors invite
      specialists in MS to participate in the discussion.

PMID- 29359736
TI  - Notes from 2017, hopes for 2018.

PMID- 29359737
TI  - Repairing the female pelvic floor: when good enough is not good enough.

PMID- 29359735
TI  - An OLTAM system for analysis of brown/beige fat thermogenic activity.
AB  - BACKGROUND/OBJECTIVES: Thermogenic fat is present in humans and emerging evidence
      indicates that increasing the content and activity of these adipocytes may lead
      to weight loss and improved metabolic health. Multiple reporter systems have been
      developed to assay thermogenic fat activity based on the transcriptional and
      translational activation of Ucp1, the key molecule that mediates nonshivering
      thermogenesis. Our study aims to develop a much-needed tool to monitor
      thermogenic fat activity through a mechanism independent of Ucp1 regulation,
      therefore effectively assaying not only canonical beta-adrenergic activation but
      also various non-UCP1-mediated thermogenic pathways that have been increasingly
      appreciated. METHODS: We detected increased luciferase activity upon thermogenic
      activation in interscapular brown and inguinal subcutaneous fat in ODD-Luc mice,
      a hypoxia reporter mouse model. We then developed an OLTAM (ODD-Luc based
      Thermogenic Activity Measurement) system to assay thermogenic fat cell activity.
      RESULTS: In both primary murine and human adipocytes and an immortalized adipose
      cell line that were transduced with the OLTAM system, luciferase activity can be
      readily measured and visualized by bioluminescence imaging in response to a
      variety of stimuli, including UCP1-independent thermogenic signaling. This system
      can offer a convenient method to assay thermogenic activity for both basic and
      translational research. CONCLUSIONS: The OLTAM system offers a convenient way to
      measure the activation of thermogenic fat and presents opportunities to discover
      novel signaling pathways and unknown compounds targeting metabolically active
      adipocytes to counteract human obesity.

PMID- 29359738
TI  - Prostate cancer: Revealing mechanisms of resistance.

PMID- 29359739
TI  - Prostate cancer: Developing CAR T cell therapy.

PMID- 29359740
TI  - The germination of germanium.

PMID- 29359742
TI  - Solution-phase reaction dynamics: Gaining control.

PMID- 29359741
TI  - Iridium-catalysed arylation of C-H bonds enabled by oxidatively induced reductive
      elimination.
AB  - Direct arylation of C-H bonds is in principle a powerful way of preparing value
      added molecules that contain carbon-aryl fragments. Unfortunately, currently
      available synthetic methods are not sufficiently effective to be practical
      alternatives to conventional cross-coupling reactions. We propose that the main
      problem lies in the late portion of the catalytic cycle where reductive
      elimination gives the desired carbon-aryl bond. Accordingly, we have developed a
      strategy where the Ir(III) centre of the key intermediate is first oxidized to
      Ir(IV). Density functional theory calculations indicate that the barrier to
      reductive elimination is reduced by nearly 19 kcal mol-1 for this oxidized
      complex compared with that of its Ir(III) counterpart. Various experiments
      confirm this prediction, affording a new methodology capable of directly
      arylating C-H bonds at room temperature with a broad substrate scope and in good
      yields. This work highlights how the oxidation states of intermediates can be
      targeted deliberately to catalyse an otherwise impossible reaction.

PMID- 29359743
TI  - Erratum: Activate lattice oxygen redox reactions in metal oxides to catalyse
      oxygen evolution.
AB  - This corrects the article DOI: 10.1038/nchem.2695.

PMID- 29359745
TI  - Mass spectrometry: Raw protein from the top down.

PMID- 29359744
TI  - An integrated native mass spectrometry and top-down proteomics method that
      connects sequence to structure and function of macromolecular complexes.
AB  - Mass spectrometry (MS) has become a crucial technique for the analysis of protein
      complexes. Native MS has traditionally examined protein subunit arrangements,
      while proteomics MS has focused on sequence identification. These two techniques
      are usually performed separately without taking advantage of the synergies
      between them. Here we describe the development of an integrated native MS and top
      down proteomics method using Fourier-transform ion cyclotron resonance (FTICR) to
      analyse macromolecular protein complexes in a single experiment. We address
      previous concerns of employing FTICR MS to measure large macromolecular complexes
      by demonstrating the detection of complexes up to 1.8 MDa, and we demonstrate the
      efficacy of this technique for direct acquirement of sequence to higher-order
      structural information with several large complexes. We then summarize the unique
      functionalities of different activation/dissociation techniques. The platform
      expands the ability of MS to integrate proteomics and structural biology to
      provide insights into protein structure, function and regulation.

PMID- 29359746
TI  - Direct alpha-C-H bond functionalization of unprotected cyclic amines.
AB  - Cyclic amines are ubiquitous core structures of bioactive natural products and
      pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an
      attractive strategy for preparing valuable functionalized amines from their
      readily available parent heterocycles, this approach has largely been limited to
      substrates that require protection of the amine nitrogen atom. In addition, most
      methods rely on transition metals and are incompatible with the presence of amine
      N-H bonds. Here we introduce a protecting-group-free approach for the alpha
      functionalization of cyclic secondary amines. An operationally simple one-pot
      procedure generates products via a process that involves intermolecular hydride
      transfer to generate an imine intermediate that is subsequently captured by a
      nucleophile, such as an alkyl or aryl lithium compound. Reactions are
      regioselective and stereospecific and enable the rapid preparation of bioactive
      amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.

PMID- 29359747
TI  - Phosphorylation, oligomerization and self-assembly in water under potential
      prebiotic conditions.
AB  - Prebiotic phosphorylation of (pre)biological substrates under aqueous conditions
      is a critical step in the origins of life. Previous investigations have had
      limited success and/or require unique environments that are incompatible with
      subsequent generation of the corresponding oligomers or higher-order structures.
      Here, we demonstrate that diamidophosphate (DAP)-a plausible prebiotic agent
      produced from trimetaphosphate-efficiently (amido)phosphorylates a wide variety
      of (pre)biological building blocks (nucleosides/tides, amino acids and lipid
      precursors) under aqueous (solution/paste) conditions, without the need for a
      condensing agent. Significantly, higher-order structures (oligonucleotides,
      peptides and liposomes) are formed under the same phosphorylation reaction
      conditions. This plausible prebiotic phosphorylation process under similar
      reaction conditions could enable the systems chemistry of the three classes of
      (pre)biologically relevant molecules and their oligomers, in a single-pot aqueous
      environment.

PMID- 29359748
TI  - Thermally activated delayed photoluminescence from pyrenyl-functionalized CdSe
      quantum dots.
AB  - The generation and transfer of triplet excitons across semiconductor nanomaterial
      molecular interfaces will play an important role in emerging photonic and
      optoelectronic technologies, and understanding the rules that govern such
      phenomena is essential. The ability to cooperatively merge the photophysical
      properties of semiconductor quantum dots with those of well-understood and
      inexpensive molecular chromophores is therefore paramount. Here we show that 1
      pyrenecarboxylic acid-functionalized CdSe quantum dots undergo thermally
      activated delayed photoluminescence. This phenomenon results from a near
      quantitative triplet-triplet energy transfer from the nanocrystals to 1
      pyrenecarboxylic acid, producing a molecular triplet-state 'reservoir' that
      thermally repopulates the photoluminescent state of CdSe through endothermic
      reverse triplet-triplet energy transfer. The photoluminescence properties are
      systematically and predictably tuned through variation of the quantum dot
      molecule energy gap, temperature and the triplet-excited-state lifetime of the
      molecular adsorbate. The concepts developed are likely to be applicable to
      semiconductor nanocrystals interfaced with molecular chromophores, enabling
      potential applications of their combined excited states.

PMID- 29359750
TI  - C-H carbonylation: In situ acyl triflates ace it.

PMID- 29359749
TI  - Biocatalytic site- and enantioselective oxidative dearomatization of phenols.
AB  - The biocatalytic transformations used by chemists are often restricted to simple
      functional-group interconversions. In contrast, nature has developed complexity
      generating biocatalytic reactions within natural product pathways. These
      sophisticated catalysts are rarely employed by chemists, because the substrate
      scope, selectivity and robustness of these catalysts are unknown. Our strategy to
      bridge the gap between the biosynthesis and synthetic chemistry communities
      leverages the diversity of catalysts available within natural product pathways.
      Here we show that, starting from a suite of biosynthetic enzymes, catalysts with
      complementary substrate scope as well as selectivity can be identified. This
      strategy has been applied to the oxidative dearomatization of phenols, a chemical
      transformation that rapidly builds molecular complexity from simple starting
      materials and cannot be accomplished with high selectivity using existing
      catalytic methods. Using enzymes from biosynthetic pathways, we have successfully
      developed a method to produce ortho-quinol products with controlled site- and
      stereoselectivity. Furthermore, we have capitalized on the scalability and
      robustness of this method in gram-scale reactions as well as multi-enzyme and
      chemoenzymatic cascades.

PMID- 29359751
TI  - Corrigendum: Structural snapshots of concerted double E-H bond activation at a
      transition metal centre.
AB  - This corrects the article DOI: 10.1038/nchem.2792.

PMID- 29359752
TI  - A dual role for a polyketide synthase in dynemicin enediyne and anthraquinone
      biosynthesis.
AB  - Dynemicin A is a member of a subfamily of enediyne antitumour antibiotics
      characterized by a 10-membered carbocycle fused to an anthraquinone, both of
      polyketide origin. Sequencing of the dynemicin biosynthetic gene cluster in
      Micromonospora chersina previously identified an enediyne polyketide synthase
      (PKS), but no anthraquinone PKS, suggesting gene(s) for biosynthesis of the
      latter were distant from the core dynemicin cluster. To identify these gene(s),
      we sequenced and analysed the genome of M. chersina. Sequencing produced a short
      list of putative PKS candidates, yet CRISPR-Cas9 mutants of each locus retained
      dynemicin production. Subsequently, deletion of two cytochromes P450 in the
      dynemicin cluster suggested that the dynemicin enediyne PKS, DynE8, may
      biosynthesize the anthraquinone. Together with 18O-labelling studies, we now
      present evidence that DynE8 produces the core scaffolds of both the enediyne and
      anthraquinone, and provide a working model to account for their formation from
      the programmed octaketide of the enediyne PKS.

PMID- 29359753
TI  - Introducing organic.

PMID- 29359754
TI  - Acceleration of a ground-state reaction by selective femtosecond-infrared-laser
      pulse excitation.
AB  - Infrared (IR) excitation of vibrations that participate in the reaction
      coordinate of an otherwise thermally driven chemical reaction are believed to
      lead to its acceleration. Attempts at the practical realization of this concept
      have been hampered so far by competing processes leading to sample heating. Here
      we demonstrate, using femtosecond IR-pump IR-probe experiments, the acceleration
      of urethane and polyurethane formation due to vibrational excitation of the
      reactants for 1:1 mixtures of phenylisocyanate and cyclohexanol, and toluene-2,4
      diisocyanate and 2,2,2-trichloroethane-1,1-diol, respectively. We measured
      reaction rate changes upon selective vibrational excitation with negligible
      heating of the sample and observed an increase of the reaction rate up to 24%.
      The observation is rationalized using reactant and transition-state structures
      obtained from quantum chemical calculations. We subsequently used IR-driven
      reaction acceleration to write a polyurethane square on sample windows using a
      femtosecond IR pulse.

PMID- 29359755
TI  - Programmable autonomous synthesis of single-stranded DNA.
AB  - DNA performs diverse functional roles in biology, nanotechnology and
      biotechnology, but current methods for autonomously synthesizing arbitrary single
      stranded DNA are limited. Here, we introduce the concept of primer exchange
      reaction (PER) cascades, which grow nascent single-stranded DNA with user
      specified sequences following prescribed reaction pathways. PER synthesis happens
      in a programmable, autonomous, in situ and environmentally responsive fashion,
      providing a platform for engineering molecular circuits and devices with a wide
      range of sensing, monitoring, recording, signal-processing and actuation
      capabilities. We experimentally demonstrate a nanodevice that transduces the
      detection of a trigger RNA into the production of a DNAzyme that degrades an
      independent RNA substrate, a signal amplifier that conditionally synthesizes long
      fluorescent strands only in the presence of a particular RNA signal, molecular
      computing circuits that evaluate logic (AND, OR, NOT) combinations of RNA inputs,
      and a temporal molecular event recorder that records in the PER transcript the
      order in which distinct RNA inputs are sequentially detected.

PMID- 29359756
TI  - Decarboxylative alkylation for site-selective bioconjugation of native proteins
      via oxidation potentials.
AB  - The advent of antibody-drug conjugates as pharmaceuticals has fuelled a need for
      reliable methods of site-selective protein modification that furnish homogeneous
      adducts. Although bioorthogonal methods that use engineered amino acids often
      provide an elegant solution to the question of selective functionalization,
      achieving homogeneity using native amino acids remains a challenge. Here, we
      explore visible-light-mediated single-electron transfer as a mechanism towards
      enabling site- and chemoselective bioconjugation. Specifically, we demonstrate
      the use of photoredox catalysis as a platform to selectivity wherein the
      discrepancy in oxidation potentials between internal versus C-terminal
      carboxylates can be exploited towards obtaining C-terminal functionalization
      exclusively. This oxidation potential-gated technology is amenable to endogenous
      peptides and has been successfully demonstrated on the protein insulin. As a
      fundamentally new approach to bioconjugation this methodology provides a
      blueprint toward the development of photoredox catalysis as a generic platform to
      target other redox-active side chains for native conjugation.

PMID- 29359757
TI  - Artificial muscle-like function from hierarchical supramolecular assembly of
      photoresponsive molecular motors.
AB  - A striking feature of living systems is their ability to produce motility by
      amplification of collective molecular motion from the nanoscale up to macroscopic
      dimensions. Some of nature's protein motors, such as myosin in muscle tissue,
      consist of a hierarchical supramolecular assembly of very large proteins, in
      which mechanical stress induces a coordinated movement. However, artificial
      molecular muscles have often relied on covalent polymer-based actuators. Here, we
      describe the macroscopic contractile muscle-like motion of a supramolecular
      system (comprising 95% water) formed by the hierarchical self-assembly of a
      photoresponsive amphiphilic molecular motor. The molecular motor first assembles
      into nanofibres, which further assemble into aligned bundles that make up
      centimetre-long strings. Irradiation induces rotary motion of the molecular
      motors, and propagation and accumulation of this motion lead to contraction of
      the fibres towards the light source. This system supports large-amplitude motion,
      fast response, precise control over shape, as well as weight-lifting experiments
      in water and air.

PMID- 29359758
TI  - Coherent wavepackets in the Fenna-Matthews-Olson complex are robust to excitonic
      structure perturbations caused by mutagenesis.
AB  - Femtosecond pulsed excitation of light-harvesting complexes creates oscillatory
      features in their response. This phenomenon has inspired a large body of work
      aimed at uncovering the origin of the coherent beatings and possible implications
      for function. Here we exploit site-directed mutagenesis to change the excitonic
      level structure in Fenna-Matthews-Olson (FMO) complexes and compare the
      coherences using broadband pump-probe spectroscopy. Our experiments detect two
      oscillation frequencies with dephasing on a picosecond timescale-both at 77 K and
      at room temperature. By studying these coherences with selective excitation pump
      probe experiments, where pump excitation is in resonance only with the lowest
      excitonic state, we show that the key contributions to these oscillations stem
      from ground-state vibrational wavepackets. These experiments explicitly show that
      the coherences-although in the ground electronic state-can be probed at the
      absorption resonances of other bacteriochlorophyll molecules because of
      delocalization of the electronic excitation over several chromophores.

PMID- 29359759
TI  - Theory-driven design of high-valence metal sites for water oxidation confirmed
      using in situ soft X-ray absorption.
AB  - The efficiency with which renewable fuels and feedstocks are synthesized from
      electrical sources is limited at present by the sluggish oxygen evolution
      reaction (OER) in pH-neutral media. We took the view that generating transition
      metal sites with high valence at low applied bias should improve the activity of
      neutral OER catalysts. Here, using density functional theory, we find that the
      formation energy of desired Ni4+ sites is systematically modulated by
      incorporating judicious combinations of Co, Fe and non-metal P. We therefore
      synthesized NiCoFeP oxyhydroxides and probed their oxidation kinetics with in
      situ soft X-ray absorption spectroscopy (sXAS). In situ sXAS studies of neutral
      pH OER catalysts indicate ready promotion of Ni4+ under low overpotential
      conditions. The NiCoFeP catalyst outperforms IrO2 and retains its performance
      following 100 h of operation. We showcase NiCoFeP in a membrane-free CO2
      electroreduction system that achieves a 1.99 V cell voltage at 10 mA cm-2,
      reducing CO2 into CO and oxidizing H2O to O2 with a 64% electricity-to-chemical
      fuel efficiency.

PMID- 29359760
TI  - Oxidase catalysis via aerobically generated hypervalent iodine intermediates.
AB  - The development of sustainable oxidation chemistry demands strategies to harness
      O2 as a terminal oxidant. Oxidase catalysis, in which O2 serves as a chemical
      oxidant without necessitating incorporation of oxygen into reaction products,
      would allow diverse substrate functionalization chemistry to be coupled to O2
      reduction. Direct O2 utilization suffers from intrinsic challenges imposed by the
      triplet ground state of O2 and the disparate electron inventories of four
      electron O2 reduction and two-electron substrate oxidation. Here, we generate
      hypervalent iodine reagents-a broadly useful class of selective two-electron
      oxidants-from O2. This is achieved by intercepting reactive intermediates of
      aldehyde autoxidation to aerobically generate hypervalent iodine reagents for a
      broad array of substrate oxidation reactions. The use of aryl iodides as
      mediators of aerobic oxidation underpins an oxidase catalysis platform that
      couples substrate oxidation directly to O2 reduction. We anticipate that
      aerobically generated hypervalent iodine reagents will expand the scope of
      aerobic oxidation chemistry in chemical synthesis.

PMID- 29359761
TI  - Labelling and determination of the energy in reactive intermediates in solution
      enabled by energy-dependent reaction selectivity.
AB  - Any long-lived chemical structure in solution is subject to statistical energy
      equilibration, so the history of any specific structure does not affect its
      subsequent reactions. This is not true for very short-lived intermediates because
      energy equilibration takes time. Here, this idea is applied to achieve the
      'energy labelling' of a reactive intermediate. The selectivity of the ring
      opening alpha-cleavage reaction of the 1-methylcyclobutoxy radical is found here
      to vary broadly depending on how the radical was formed. Reactions that provide
      little excess energy to the intermediate lead to a high selectivity in the
      subsequent cleavage (measured as a kinetic isotope effect), whereas reactions
      that provide more excess energy to the intermediate exhibit a lower selectivity.
      Accounting for the expected excess energy allows the prediction of the observed
      product ratios and, in turn, the product ratios can be used to determine the
      energy present in an intermediate.

PMID- 29359762
TI  - DNA-imprinted polymer nanoparticles with monodispersity and prescribed DNA-strand
      patterns.
AB  - As colloidal self-assembly increasingly approaches the complexity of natural
      systems, an ongoing challenge is to generate non-centrosymmetric structures. For
      example, patchy, Janus or living crystallization particles have significantly
      advanced the area of polymer assembly. It has remained difficult, however, to
      devise polymer particles that associate in a directional manner, with controlled
      valency and recognition motifs. Here, we present a method to transfer DNA
      patterns from a DNA cage to a polymeric nanoparticle encapsulated inside the cage
      in three dimensions. The resulting DNA-imprinted particles (DIPs), which are
      'moulded' on the inside of the DNA cage, consist of a monodisperse crosslinked
      polymer core with a predetermined pattern of different DNA strands covalently
      'printed' on their exterior, and further assemble with programmability and
      directionality. The number, orientation and sequence of DNA strands grafted onto
      the polymeric core can be controlled during the process, and the strands are
      addressable independently of each other.

PMID- 29359763
TI  - A general approach to intermolecular carbonylation of arene C-H bonds to ketones
      through catalytic aroyl triflate formation.
AB  - The development of metal-catalysed methods to functionalize inert C-H bonds has
      become a dominant research theme in the past decade as an approach to efficient
      synthesis. However, the incorporation of carbon monoxide into such reactions to
      form valuable ketones has to date proved a challenge, despite its potential as a
      straightforward and green alternative to Friedel-Crafts reactions. Here we
      describe a new approach to palladium-catalysed C-H bond functionalization in
      which carbon monoxide is used to drive the generation of high-energy
      electrophiles. This offers a method to couple the useful features of metal
      catalysed C-H functionalization (stable and available reagents) and electrophilic
      acylations (broad scope and selectivity), and synthesize ketones simply from aryl
      iodides, CO and arenes. Notably, the reaction proceeds in an intermolecular
      fashion, without directing groups and at very low palladium-catalyst loadings.
      Mechanistic studies show that the reaction proceeds through the catalytic build
      up of potent aroyl triflate electrophiles.

PMID- 29359764
TI  - Structure-based inhibitors of tau aggregation.
AB  - Aggregated tau protein is associated with over 20 neurological disorders, which
      include Alzheimer's disease. Previous work has shown that tau's sequence segments
      VQIINK and VQIVYK drive its aggregation, but inhibitors based on the structure of
      the VQIVYK segment only partially inhibit full-length tau aggregation and are
      ineffective at inhibiting seeding by full-length fibrils. Here we show that the
      VQIINK segment is the more powerful driver of tau aggregation. Two structures of
      this segment determined by the cryo-electron microscopy method micro-electron
      diffraction explain its dominant influence on tau aggregation. Of practical
      significance, the structures lead to the design of inhibitors that not only
      inhibit tau aggregation but also inhibit the ability of exogenous full-length tau
      fibrils to seed intracellular tau in HEK293 biosensor cells into amyloid. We also
      raise the possibility that the two VQIINK structures represent amyloid polymorphs
      of tau that may account for a subset of prion-like strains of tau.

PMID- 29359765
TI  - Silicon chemistry in zero to three dimensions: from dichlorosilylene to
      silafullerane.
AB  - Silylenes and silanides, prominent Si(ii) species, are not only interesting in
      their own right, but also constitute important building blocks in oligosilane and
      organosilane chemistry. The past decade has witnessed tremendous advances in the
      understanding of the ambiphilic behavior of silylenes and the nucleophilic
      properties of silanides, as well as the mutual relationships between both
      species. Especially the readily available SiCl2/[SiCl3]- system is intriguing,
      because it features highly functionalized silicon centers, amenable to late-stage
      modifications. Moreover, SiCl2 and [SiCl3]- are interconvertible by mere chloride
      association/dissociation. This Feature Article first provides a brief
      introduction to isolable (functionalized) silylenes and silanides and then
      focusses on the SiCl2/[SiCl3]- couple. Classical high-temperature protocols for
      the generation of SiCl2 are juxtaposed with convenient recent solution phase
      methods that provide access to R3N-SiCl2 and [SiCl3]-via deprotonation of HSiCl3
      or the amine-/chloride-induced disproportionation of Si2Cl6. We give a
      comprehensive overview of key mechanistic issues and highlight the utility of R3N
      SiCl2 and [SiCl3]- for the synthesis of open-chain and cyclic oligosilanes as
      well as nanoscale, fullerene-type silicon clusters.

PMID- 29359766
TI  - A lipid-based cell penetrating nano-assembly for RNAi-mediated anti-angiogenic
      cancer therapy.
AB  - Limited tumor tissue penetration is one of the key impeding factors retarding
      successful in vivo exploitations of anti-angiogenic cancer therapy. Herein we
      report on the design of a cell penetrating peptide-decorated lipid nano-assembly
      which, upon systemic administration, induces significant mouse tumor growth
      inhibition via enhanced tumor infiltration of encapsulated anti-angiogenic siRNA.

PMID- 29359767
TI  - Computational studies on ground and excited state charge transfer properties of
      peptidomimetics.
AB  - Chemical modifications at various peptide positions result in peptidomimetics
      with unique physical and chemical properties that can be used for a range of
      applications. Among many peptidomimetics, ureidopeptides are interesting due to
      their ability to act as donor-bridge-acceptor systems through which charge
      transfer occurs in one direction and can be triggered by an electrochemical pulse
      without perturbing the nuclear position. In this regard, some UP mimetics with
      different chromophoric units are studied in this work to understand their role
      using DFT based methods. Computational results and natural charge analysis
      provide evidence for the extensive contribution of the substituents to the
      excitation and hole migration dynamics. Further, the results show that the UP
      backbone preserves its uni-directional charge transfer phenomenon from the ureido
      to carboxylate terminal irrespective of the terminal groups and position.
      However, the substituent affects the excitation energies and the time scales of
      the hole migration. Among the substituents studied here, fluorine migrates to the
      hole within a shorter time scale while phenyl groups take longer.

PMID- 29359770
TI  - An ultra-small NiFe2O4 hollow particle/graphene hybrid: fabrication and
      electromagnetic wave absorption property.
AB  - Herein, ultra-small NiFe2O4 hollow particles, with the diameter and wall
      thickness of only 6 and 1.8 nm, respectively, were anchored on a graphene surface
      based on the nanoscale Kirkendall effect. The hybrid exhibits an excellent
      electromagnetic wave absorption property, comparable or superior to that of most
      reported absorbers. Our strategy may open a way to grow ultra-small hollow
      particles on graphene for applications in many fields such as eletromagnetic wave
      absorption and energy storage and conversion.

PMID- 29359771
TI  - Correction: Rate constants, processivity, and productive binding ratio of
      chitinase A revealed by single-molecule analysis.
AB  - Correction for 'Rate constants, processivity, and productive binding ratio of
      chitinase A revealed by single-molecule analysis' by Akihiko Nakamura et al.,
      Phys. Chem. Chem. Phys., 2018, DOI: .

PMID- 29359772
TI  - Ultrafine Co1-xS nanoparticles embedded in a nitrogen-doped porous carbon hollow
      nanosphere composite as an anode for superb sodium-ion batteries and lithium-ion
      batteries.
AB  - Cobalt sulfides are attractive as intriguing candidates for anodes in SIBs and
      LIBs owing to their unique chemical and physical properties. In this study, a
      precursor of Co1-xS with a uniform and hollow nanospherical architecture is
      obtained with a high yield via a mild solvothermal method in the presence of 2
      methylimidazole at first. Then, Co1-xS, Co1-xS/C (ultrafine Co1-xS nanoparticles
      embedded in the shells of the nitrogen-doped porous carbon hollow nanosphere),
      and Co1-xS@C (Co1-xS nanoparticles entirely covered by an external amorphous
      carbon layer) were selectively fabricated via direct calcination or PPy coating &
      calcination of the obtained precursor. Co1-xS/C shows best electrochemical
      performance than the other two materials as anodes for sodium-ion batteries
      (SIBs). Besides the excellent rate performance, a high reversible discharge
      capacity of 320 mA g-1 can be retained after 130 cycles at 1 A g-1. The
      impressive performance may be attributed to the unique structure, higher
      conductivity, and more active sites of Co1-xS/C. In addition, 559 mA h g-1 was
      maintained after 100 cycles at 500 mA g-1 when the Co1-xS/C composite was applied
      as an anode in lithium-ion batteries (LIBs). The high reversible capacity,
      excellent cycle stability combined with the facile synthesis procedure render Co1
      xS/C a prospective anode material for rechargeable batteries.

PMID- 29359775
TI  - Correction: Escape of anions from geminate recombination in THF due to charge
      delocalization.
AB  - Correction for 'Escape of anions from geminate recombination in THF due to charge
      delocalization' by Hung-Cheng Chen et al., Phys. Chem. Chem. Phys., 2017, 19,
      32272-32285.

PMID- 29359776
TI  - Solvent-sensitive signs and magnitudes of circularly polarised luminescence and
      circular dichroism spectra: probing two phenanthrenes as emitters endowed with
      BINOL derivatives.
AB  - A C2-symmeric binaphthyl framework bearing phenanthrene as the emitter exhibited
      circularly polarised luminescence (CPL) in dilute solutions. The CPL and circular
      dichroism signs of the luminophores were altered by solvents (chloroform,
      methanol, acetonitrile, and dimethylformamide). DFT and TD-DFT calculations
      indicated that the dihedral angle between the phenanthrene and naphthyl rings was
      responsible for the apparent sign inversion. The role of solvent molecules in the
      ground and photoexcited states was discussed based on Hansen solubility
      parameters (delta, deltad, deltap and deltah).

PMID- 29359777
TI  - Correction: Model of protocell compartments - dodecyl hydrogen sulfate vesicles.
AB  - Correction for 'Model of protocell compartments - dodecyl hydrogen sulfate
      vesicles' by Bin Liu et al., Phys. Chem. Chem. Phys., 2018, DOI: .

PMID- 29359778
TI  - 808 nm excited energy migration upconversion nanoparticles driven by a Nd3+
      Trinity system with color-tunability and superior luminescence properties.
AB  - We have developed energy migration upconversion (EMU) nanoparticles (UCNPs) with
      optimal Nd3+-sensitization under excitation of an 808 nm laser to avoid over
      heating effects caused by a 980 nm laser while maximizing the excitation
      efficiency. To realize efficient 808 nm sensitization, a "Nd3+-Trinity system"
      was implemented in the energy migration upconversion (EMU) cores
      (NaGdF4:Yb,Tm@NaGdF4:Yb,X, X = Eu/Tb), resulting in a core-multishell structure
      of EMU cores (accumulation layer@activation layer)@transition layer@harvest
      layer@activation layer. The spatially separated dopants and optimized Yb3+/Nd3+
      content effectively prevented severe quenching events in the UCNPs and their Nd3+
      sensitized EMU-based photoluminescence mechanism was studied under 808 nm
      excitation. These Nd3+-Trinity EMU system UCNPs presented enhanced upconversion
      luminescence and prolonged lifetime compared to the 980 nm excited UCNPs of the
      EMU system. It is proposed that 975 nm and 1056 nm NIR photons induced from the
      Nd3+ -> Yb3+ energy transfer facilitate the Tm3+ accumulation process due to the
      matched energy gaps, which contributes to the extended lifetimes. More
      importantly, the synthesized UCNPs had a small average size of sub-15 nm and they
      not only exhibited color-tunability via Eu3+/Tb3+ activators, but also released a
      larger portion of Tm3+ red emission at 647 nm and had better penetration ability
      in water under 808 nm excitation, which are favorable for bioimaging
      applications.

PMID- 29359780
TI  - Correction: Planar vs. three-dimensional X62-, X2Y42-, and X3Y32- (X, Y = B, Al,
      Ga) metal clusters: an analysis of their relative energies through the turn
      upside-down approach.
AB  - Correction for 'Planar vs. three-dimensional X62-, X2Y42-, and X3Y32- (X, Y = B,
      Al, Ga) metal clusters: an analysis of their relative energies through the turn
      upside-down approach by Ouissam El Bakouri et al., Phys. Chem. Chem. Phys., 2016,
      18, 21102-21110.

PMID- 29359781
TI  - Generating plasmonic heterostructures by cation exchange and redox reactions of
      covellite CuS nanocrystals with Au3+ ions.
AB  - We demonstrate the fabrication of various types of heterostructures, including
      core-shells and dimers. This is achieved by reacting platelet-shaped covellite
      (CuS) nanocrystals (NCs) with Au3+ ions under various reaction conditions: the
      exposure of CuS NCs to Au3+ ions, in the presence or in the absence of ascorbic
      acid (AA), leads to the formation of CuS@Au core-shell nanostructures; the
      reaction of CuS NCs with Au3+ ions in the presence of oleylamine (OM) leads to
      the formation of CuS@Au2S; the presence of both OM and AA leads to the formation
      of Au/CuS dimers. Depending on which condition is chosen, either cation exchange
      (CE) between gold and copper ions is predominant (leading to amorphous Au2S) or
      the reduction of Au3+ leads to the nucleation of metallic Au domains (which are
      operated by the AA). In the heterostructures achieved by CE, the Au2S shell is
      almost entirely amorphous, and can be converted to polycrystalline upon electron
      beam irradiation. Finally, when both oleylamine and AA are present in the
      reaction environment, Au/CuS dimers are formed due to the reduction of Au3+ to
      metallic Au domains which nucleate on top of the CuS seeds. The experimental dual
      plasmonic bands of the CuS@Au core-shells and Au/CuS dimers are in agreement with
      the theoretical optical simulations. The procedures described here enable the
      synthesis of core-shell nanostructures with tunable localized surface plasmon
      resonances (LSPRs) in the near-infrared (NIR) region, and of plasmonic
      metal/semiconductor heterostructures with LSPRs in both the NIR and the visible
      regions.

PMID- 29359782
TI  - Suppression of human breast cancer cells by tectorigenin through downregulation
      of matrix metalloproteinases and MAPK signaling in vitro.
AB  - Breast cancer is a major life-threatening malignancy and is the second highest
      cause of mortality. The aim of the present study was to investigate the effects
      of tectorigenin (Tec), a Traditional Chinese Medicine, against human breast
      cancer cells in vitro. MDA-MB-231 and MCF-7 human breast cancer cells were
      treated with various concentrations of Tec. Cell proliferation was evaluated
      using the Cell Counting kit-8 assay, and apoptosis and the cell cycle were
      examined by flow cytometry. The migratory and invasive abilities of these cells
      were detected by Transwell and Matrigel assays, respectively. Metastasis-,
      apoptosis- and survival-related gene expression levels were measured by reverse
      transcription-quantitative polymerase chain reaction and western blotting. The
      results indicated that Tec was able to inhibit the proliferation of MDA-MB-231
      and MCF-7 cells in a dose- and time-dependent manner. Furthermore, Tec treatment
      induced apoptosis and G0/G1-phase arrest, and inhibited cell migration and
      invasion. Tec treatment decreased the expression of matrix metalloproteinase
      (MMP)-2, MMP9, BCL-2, phosphorylated-AKT and components of the mitogen-activated
      protein kinase (MAPK) signaling pathway, and increased the expression of BCL-2
      associated X, cleaved poly [ADP-ribose] polymerase and cleaved caspase-3. In
      conclusion, Tec treatment suppressed human breast cancer cells through the
      downregulation of AKT and MAPK signaling and the upregulated expression and/or
      activity of the caspase family in vitro. Therefore, Tec may be a potential
      therapeutic drug to treat human breast cancer.

PMID- 29359783
TI  - Aberrant methylation of HTATIP2 and UCHL1 as a predictive biomarker for
      cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) is the most common primary liver cancer in Northeastern
      Thailand where liver fluke infection is highly endemic. Although aberrant DNA
      methylation in CCA has been reported by several investigators, little is known
      regarding the associations between them. In the present study, the results
      obtained from our previously published methylation array were analyzed and 10
      candidate genes involved in DNA repair [protein phosphatase 4 catalytic subunit
      (PPP4C)], apoptosis [runt related transcription factor 3 (RUNX3), interferon
      regulatory factor 4 (IRF4), ubiquitin C-terminal hydrolase L1 (UCHL1) and tumor
      protein p53 inducible protein 3 (TP53I3)], cell proliferation [cyclin D2 (CCND2)
      and Ras association domain family member 1 (RASSF1)], drug metabolism [aldehyde
      dehydrogenase 1 family member A3 (ALDH1A3) and solute carrier family 29 member 1
      (SLC29A1)] and angiogenesis [human immunodeficiency virus-1 tat interactive
      protein 2 (HTATIP2)] were selected for quantification of their methylation levels
      in 54 CCA and 19 adjacent normal tissues using methylation-sensitive high
      resolution melting. The associations between the methylation status of the
      individual genes and clinical parameters were statistically analyzed. High
      methylation levels were observed in UCHL1, IRF4, CCND2, HTATIP2 and TP53I3. The
      median methylation level of UCHL1 was 57.3% (range, 3.15 to 88.7%) and HTATIP2
      was 13.6% (range, 7.5 to 36.7%). By contrast, low methylation of HTATIP2 and
      UCHL1 was identified in adjacent normal tissues. The methylation status of
      HTATIP2 and UCHL1 was associated with patients' overall survival. CCA patients
      with high methylation of HTATIP2 and low methylation of UCHL1 exhibited longer
      overall survival. In addition, multivariate Cox regression analysis demonstrated
      that UCHL1 methylation was an independent factor for CCA with hazard ratio of
      1.81 (95% confidence interval, 1.01-3.25) in high methylation group. The
      combination of HTATIP2 and UCHL1 methylation status strongly supported their
      potential predictive biomarker in which patients with CCA who had high
      methylation of HTATIP2 and low methylation of UCHL1 showed longer overall
      survival than those with low HTATIP2 methylation and high UCHL1 methylation. In
      conclusion, the present study revealed the value of aberrant DNA methylation of
      HTATIP2 and UCHL1, which may serve as a potential predictive biomarker for CCA.

PMID- 29359784
TI  - Puerarin protects endothelial progenitor cells from damage of angiotensin II via
      activation of ERK1/2-Nrf2 signaling pathway.
AB  - Endothelial progenitor cell (EPC) dysfunction is associated with the formation of
      carotid atherosclerosis. It has been demonstrated that angiotensin II (Ang II)
      may impair the function of EPCs and puerarin, a natural product, possesses
      cardiovascular protective effects against oxidative stress and inflammation.
      Therefore, the present study aimed to investigate the beneficial effects of
      puerarin in Ang II-induced EPC injury, and to elucidate the underlying
      mechanisms. Treatment with Ang II suppressed EPC proliferation and migration,
      increased the expression of the senescence marker beta-galactosidase, and the
      adhesion molecules intracellular adhesion molecule-1 and vascular cell adhesion
      molecule-1. However, the above effects were markedly alleviated by treatment with
      puerarin in a dose-dependent manner (1, 10 and 100 uM). In addition, Ang II
      significantly increased reactive oxygen species production and the levels of the
      inflammatory cytokine tumor necrosis factor-alpha and interleukin-6. Notably,
      these effects were reversed by puerarin. However, it was identified that the
      impaired EPC functions were due to inhibition of the phosphorylation of
      extracellular signal-regulated kinase 1 and 2 (ERK1/2) and the degradation of
      nuclear factor erythroid 2 like 2 (Nrf2), and treatment with puerarin activated
      the ERK1/2-Nrf2 signaling pathway. The results of the present study indicated
      that puerarin protected Ang II-induced EPC dysfunction via activation of the
      ERK1/2-Nrf2 signaling pathway.

PMID- 29359785
TI  - The association between an endothelial nitric oxide synthase gene polymorphism
      and coronary heart disease in young people and the underlying mechanism.
AB  - With the development of molecular biological technology, the association between
      genes and diseases has drawn increasing attention of researchers; the endothelial
      nitric oxide synthase (eNOS) gene has been reported to be a candidate gene for
      cardiovascular disease (CHD). The present study aimed to investigate the
      association between a polymorphism of eNOS and the risk of CHD in young people
      (<=40 years old), in addition to the underlying mechanism. A total of 234 cases
      of CHD in young individuals were collected as the CHD group and 228 cases of
      healthy individuals as the control group. Peripheral blood was collected and the
      genotype of the eNOS G894T polymorphism was identified by polymerase chain
      reaction-restriction fragment length polymorphism, the gene frequency was
      calculated and the distributions of genotype and allele frequency between the two
      groups were compared. Bioinformatics tools were employed to analyze the
      differences in the local protein structures of the eNOS G894T polymorphism and
      the biological mechanism was preliminary discussed. The results demonstrated that
      there were significant differences in the distribution of genotype frequency and
      allele frequency of the eNOS G894T gene polymorphism between the CHD group and
      control group (P<0.05). The risk of CHD in GT and TT genotypes were higher
      compared with the GG genotype (P<0.05). The G894T polymorphism led to Glu298Asp
      mutation of encoded protein, which is within the active site of eNOS, and partial
      structures of the protein were converted from random coil to alpha-helix. In
      conclusion, the eNOS G894T gene polymorphism was associated with the occurrence
      and development of CHD in young people. The potential mechanism is that the G894T
      polymorphism leads to altered protein structure, which affects the function of
      eNOS in generating nitric oxide and cardiovascular diastole. The results of the
      present study suggested a potential target gene for the prevention and treatment
      of CHD in young people (<=40 years old).

PMID- 29359786
TI  - Uric acid upregulates the adiponectin-adiponectin receptor 1 pathway in renal
      proximal tubule epithelial cells.
AB  - Adiponectin (APN) is a protein hormone that is primarily derived from adipocytes.
      It can also be secreted by renal cells. Hypoadiponectinemia has been documented
      in patients with hyperuricemia, however, whether soluble uric acid (SUA)
      regulates the expression of APN and APN receptor 1 (AdipoR1) in renal proximal
      tubule epithelial cells (PTECs) remains to be elucidated. The present study
      investigated the expression of APN and AdipoR1 in cultured PTECs that were
      exposed to SUA through immunofluorescence and western blot analysis. In addition,
      Sprague-Dawley rats with oxonic acid-induced hyperuricemia (HUA) with or without
      febuxostat treatment were employed as an animal model to measure 24 h urine
      protein, serum creatinine, urea nitrogen, uric acid and homeostasis model
      assessment of insulin resistance. Renal pathology was evaluated using hematoxylin
      and eosin and immunohistochemical staining. APN and AdipoR1 expression in the
      renal cortex were evaluated by western blotting. The results demonstrated that,
      in PTECs, the expression of APN and AdipoR1 was constant and increased upon SUA
      exposure. Similar observations were made within the proximal renal tubules of
      rats, and the oxonic acid-induced increases in APN and AdipoR1 were offset by
      febuxostat treatment. Furthermore, SUA-treated PTECs exhibited an increase in the
      expression of NLR family pyrin domain-containing (NLRP) 3, which was dose
      dependent. NLRP3 expression was also significantly increased in the renal cortex
      of HUA rats compared with control and febuxostat-treated rats. In conclusion, SUA
      enhanced the expression of APN and AdipoR1 in PTECs, which was associated with an
      increase in NLRP3 expression. The APN-AdipoR1 pathway was demonstrated to have an
      important role in in vitro and in vivo models of renal proximal tubule
      inflammatory injury. Therefore, this pathway may be a potential therapy target in
      urate nephropathy.

PMID- 29359787
TI  - The differential effect of basic fibroblast growth factor and stromal cell
      derived factor-1 pretreatment on bone morrow mesenchymal stem cells osteogenic
      differentiation potency.
AB  - In situ tissue engineering has become a novel strategy to repair periodontal/bone
      tissue defects. The choice of cytokines that promote the recruitment and
      proliferation, and potentiate and maintain the osteogenic differentiation ability
      of mesenchymal stem cells (MSCs) is the key point in this technique. Stromal cell
      derived factor-1 (SDF-1) and basic fibroblast growth factor (bFGF) have the
      ability to promote the recruitment, and proliferation of MSCs; however, the
      differential effect of SDF-1 and bFGF pretreatment on MSC osteogenic
      differentiation potency remains to be explored. The present study comparatively
      observed osteogenic differentiation of bone morrow MSCs (BMMSCs) pretreated by
      bFGF or SDF-1 in vitro. The gene and protein expression levels of alkaline
      phosphatase (ALP), runt related transcription factor 2 (Runx-2) and bone
      sialoprotein (BSP) were detected using reverse transcription-quantitative
      polymerase chain reaction and western blotting. The results showed that the
      expression of ALP mRNA on day 3, and BSP and Runx-2 mRNA on day 7 in the bFGF
      pretreatment group was significantly higher than those in SDF-1 pretreatment
      group. Expression levels of Runx-2 mRNA, and ALP and Runx-2 protein on day 3 in
      the SDF-1 pretreatment group were higher than those in the bFGF pretreatment
      group. However, there was no significant difference in osteogenic differentiation
      ability on day 14 and 28 between the bFGF- or SDF-1-pretreatment groups and the
      control. In conclusion, bFGF and SDF-1 pretreatment inhibits osteogenic
      differentiation of BMMSCs at the early stage, promotes it in the medium phase,
      and maintains it in the later stage during osteogenic induction, particularly at
      the mRNA level. Out of the two cytokines, bFGF appeared to have a greater effect
      on osteogenic differentiation.

PMID- 29359789
TI  - Glutamine synthetase gene knockout-human embryonic kidney 293E cells for stable
      production of monoclonal antibodies.
AB  - Previously, it was inferred that a high glutamine synthetase (GS) activity in
      human embryonic kidney (HEK) 293E cells results in elevated resistance to
      methionine sulfoximine (MSX) and consequently hampers GS-mediated gene
      amplification and selection by MSX. To overcome this MSX resistance in HEK293E
      cells, a GS-knockout HEK293E cell line was generated using the CRISPR/Cas9 system
      to target the endogenous human GS gene. The GS-knockout in the HEK293E cell line
      (RK8) was confirmed by Western blot analysis of GS and by observation of
      glutamine-dependent growth. Unlike the wild type HEK293E cells, the RK8 cells
      were successfully used as host cells to generate a recombinant HEK293E cell line
      (rHEK293E) producing a monoclonal antibody (mAb). When the RK8 cells were
      transfected with the GS expression vector containing the mAb gene, rHEK293E cells
      producing the mAb could be selected in the absence as well as in the presence of
      MSX. The gene copies and mRNA expression levels of the mAb in rHEK293E cells were
      also quantified using qRT-PCR. Taken together, the GS-knockout HEK293E cell line
      can be used as host cells to generate stable rHEK293E cells producing a mAb
      through GS-mediated gene selection in the absence as well as in the presence of
      MSX.

PMID- 29359788
TI  - MicroRNA expression profiles in benign prostatic hyperplasia.
AB  - Although alterations in microRNA (miRNA) expression have been previously
      investigated prostate cancer, the expression of miRNAs specifically in benign
      prostate hyperplasia (BPH) of the prostatic stroma remains to be fully
      elucidated. In the present study, miRNAs and gene expression profiles were
      investigated using microarray analysis and reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) in BPH tissue to clarify the associations
      between miRNA expression and target genes. Prostate tissue samples from five
      patients with BPH and five healthy men were analyzed using human Affymetrix miRNA
      and mRNA microarrays and differentially expressed miRNAs were validated using RT
      qPCR with 30 BPH and 5 healthy control samples. A total of 8 miRNAs, including
      miRNA (miR)-96-5p, miR-1271-5p, miR-21-3p, miR-96-5p, miR-181a-5p, miR-143-3p,
      miR-4428 and miR-106a-5p were upregulated and 8 miRNAs (miR-16-5p, miR-19b-5p,
      miR-940, miR-25, miR-486-3p, miR-30a-3p, let-7c and miR-191) were downregulated.
      Additionally, miR-96-5p was demonstrated to have an inhibitory effect on the mRNA
      expression levels of the following genes: Mechanistic target of rapamycin (MTOR),
      RPTOR independent companion of MTOR complex 2, syntaxin 10, autophagy-related
      protein 9A, zinc finger E-box binding homeobox 1, caspase 2 and protein kinase c
      epsilon. Additionally, 16 differentially expressed miRNAs were identified using
      RT-qPCR analysis. This preliminary study provides a solid basis for a further
      functional study to investigate the underlying regulatory mechanisms of BPH.

PMID- 29359790
TI  - Pre- and post-transplant minimal residual disease predicts relapse occurrence in
      children with acute lymphoblastic leukaemia.
AB  - Relapse remains the leading cause of treatment failure in children with acute
      lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell
      transplantation (HSCT). We retrospectively investigated the prognostic role of
      minimal residual disease (MRD) before and after HSCT in 119 children transplanted
      in complete remission (CR). MRD was measured by polymerase chain reaction in bone
      marrow samples collected pre-HSCT and during the first and third trimesters after
      HSCT (post-HSCT1 and post-HSCT3). The overall event-free survival (EFS) was 50%.
      The cumulative incidence of relapse and non-relapse mortality was 41% and 9%. Any
      degree of detectable pre-HSCT MRD was associated with poor outcome: EFS was 39%
      and 18% in patients with MRD positivity <1 * 10-3 and >=1 * 10-3 , respectively,
      versus 73% in MRD-negative patients (P < 0.001). This effect was maintained in
      different disease remissions, but low-level MRD had a very strong negative impact
      only in patients transplanted in second or further CR. Also, MRD after HSCT
      enabled patients to be stratified, with increasing MRD between post-HSCT1 and
      post-HSCT3 clearly defining cohorts with a different outcome. MRD is an important
      prognostic factor both before and after transplantation. Given that MRD
      persistence after HSCT is associated with dismal outcome, these patients could
      benefit from early discontinuation of immunosuppression, or pre-emptive immuno
      therapy.

PMID- 29359791
TI  - Insights on the structure-activity relationship of peptides derived from
      Sticholysin II.
AB  - Sticholysin II (StII) is a pore-forming actinoporin from the sea anemone
      Stichodactyla helianthus. A mechanistic model of its action has been proposed:
      proteins bind to cell membrane, insert their N-termini into the lipid core and
      assemble into homo-tetramer pores responsible for host-cell death. Because very
      likely the first 10 residues of StII N-terminus are critical for membrane
      penetration, to dissect the molecular details of that functionality, we studied
      two synthetic peptides: StII1-30 and StII16-35 . They show diverse haemolytic and
      candidacidal activity that correlate with distinct orientations in SDS micelles.
      NMR shows that StII1-30 partly inserts into the micelle, while StII16-35 lays on
      the micelle surface. These results justify the diverse concentration dependence
      of their candidacidal activity supposing a different mechanism of action and
      providing new hints on StII lytic activity at molecular level. Biotechnological
      application of these peptides, focused on the development of therapeutic
      immunocomplexes, may be envisaged.

PMID- 29359792
TI  - PDCD1 and CTLA4 polymorphisms affect the susceptibility to, and clinical features
      of, chronic immune thrombocytopenia.
AB  - Programmed death-1 (PD-1, PDCD1) and cytotoxic T lymphocyte-associated antigen-4
      (CTLA-4, CTLA4) play central roles in immune checkpoint pathways. Single
      nucleotide polymorphisms (SNPs) of PDCD1 and CTLA4 have been reported to be
      associated with susceptibility to some autoimmune diseases. However, the
      potential association between SNPs in these immune checkpoint genes and risk of
      chronic immune thrombocytopenia (cITP) remain controversial and obscure. The aims
      of this study were to clarify the influence of PDCD1 and CTLA4 SNPs on the risk
      of developing cITP and its clinical features. We obtained genomic DNA from 119
      patients with cITP and 223 healthy controls; their genotypes were determined by
      the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method. Patients with cITP had a significantly higher frequency of the PDCD1
      +7209 TT genotype compared with healthy controls. The CTLA4 -1577 GG genotype and
      CT60 GG genotype showed higher frequencies of platelet count <5 * 109 /l at
      diagnosis, minimum platelet count <5 * 109 /l, and bleeding symptoms. Moreover,
      the PDCD1 -606 AA genotype and +63379 TT genotype were significantly associated
      with a lower number of patients who achieved a complete response to prednisolone
      treatment. Our results suggest that the immune checkpoint polymorphisms may
      affect the susceptibility to the clinical features of cITP, and treatment
      response of the affected patients.

PMID- 29359793
TI  - Correlates of students' internalization and defiance of classroom rules: A self
      determination theory perspective.
AB  - BACKGROUND: It is generally accepted that well-established classroom rules
      prevent problem behaviour, while also supporting students' achievement gains.
      Yet, there might be considerable variability in students' underlying motives to
      comply or refrain from complying with classroom rules, with some students
      adhering to them because they fully accept them as their own, and others feeling
      compelled by external or internal demands to do so or even defying the rules
      altogether. AIMS: Grounded in self-determination theory, this study aimed to
      examine whether students' reasons for following (i.e., internalization) and for
      refraining from following (i.e., defiance) classroom rules differentially and
      uniquely predict student outcomes, including feelings of resentment, acting out,
      cheating, and truancy. SAMPLE: A total of 1006 students (46.7% boys; M = 14.18
      years +/- 1.73) out of 56 different secondary school classes participated in the
      study. METHODS: Students were invited to fill out an online survey about
      experiences with their head teacher. RESULTS: For three out of four outcomes,
      identified regulation and external regulation to follow classroom rules were
      found to be, respectively, negatively and positively related, whereas a null
      relationship with introjected rule following was found. Controlled non-rule
      following was most strongly predictive of maladaptive functioning, as indexed by
      more feelings of resentment, acting out, cheating, and truancy. CONCLUSIONS:
      Whereas students' ownership of rules is critical to prevent classroom
      misbehaviour, their pressured non-adherence is a risk factor.

PMID- 29359794
TI  - Association of EZH2 protein expression by immunohistochemistry in myelodysplasia
      related neoplasms with mutation status, cytogenetics and clinical outcomes.

PMID- 29359795
TI  - Recent advances in developing specific therapies for haemophilia.
AB  - Haemophilia therapy has undergone very rapid evolution in the last 10 years. The
      major limitation of current replacement therapy is the short half-life of factors
      VIII and IX. These half-lives have been extended by the addition of various
      moieties, allowing less frequent infusion regimens. Entirely novel approaches
      have also entered the clinic, including a bispecific antibody that mimics factor
      VIII and strategies that rebalance the haemostatic mechanism by reducing
      antithrombin through inhibition of synthesis. These two treatments are available
      by subcutaneous injection at infrequent intervals and both can be used in
      patients with neutralising antibodies (inhibitors). Finally, a cure may be on the
      horizon with preliminary evidence of success for gene therapy in haemophilia B
      and A.

PMID- 29359796
TI  - The DiPEP (Diagnosis of PE in Pregnancy) biomarker study: An observational cohort
      study augmented with additional cases to determine the diagnostic utility of
      biomarkers for suspected venous thromboembolism during pregnancy and puerperium.
AB  - This study aimed to estimate the diagnostic utility of biomarkers for suspected
      venous thromboembolism (VTE) in pregnancy and the puerperium. Research
      nurses/midwives collected blood samples from 310 pregnant/postpartum women with
      suspected pulmonary emboli (PE) and 18 with diagnosed deep vein thrombosis (DVT).
      VTE was diagnosed using imaging, treatment and adverse outcome data. Primary
      analysis was limited to women with conclusive imaging (36 with VTE, 247 without).
      The area under the curve (AUC) for each biomarker was: activated partial
      thromboplastin time 0.669 (95% confidence interval 0.570-0.768), B-type
      natriuretic peptide 0.549 (0.453-0.645), C-reactive protein 0.542 (0.445-0.639),
      Clauss fibrinogen 0.589 (0.476-0.701), D-Dimer (by enzyme-linked immunosorbent
      assay) 0.668 (0.561-0.776), near-patient D-Dimer 0.651 (0.545-0.758), mid
      regional pro-atrial natriuretic peptide 0.524 (0.418-0.630), prothrombin fragment
      1 + 2 0.562 (0.462-0.661), plasmin-antiplasmin complexes 0.639 (0.536-0.742),
      prothombin time 0.613 (0.508-0.718), thrombin generation lag time 0.702 (0.598
      0.806), thrombin generation endogenous potential 0.559 (0.437-0.681), thrombin
      generation peak 0.596 (0.478-0.715), thrombin generation time to peak 0.655
      (0.541-0.769), soluble tissue factor 0.531 (0.424-0.638) and serum troponin 0.597
      (0.499-0.695). No diagnostically useful threshold for diagnosing or ruling out
      VTE was identified. In pregnancy and the puerperium, conventional and candidate
      biomarkers have no utility either for their negative or positive predictive value
      in the diagnosis of VTE.

PMID- 29359797
TI  - Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment
      aspects.
AB  - Mantle cell lymphoma (MCL) is a lymphoproliferative disorder comprising about 6
      10% of all B cell lymphoma cases. Ibrutinib is an inhibitor of Bruton tyrosine
      kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways.
      Although treatment with ibrutinib has significantly improved the outcome of MCL
      patients, approximately one-third of the patients have primary drug resistance
      while others appear to develop acquired resistance. Understanding the molecular
      events leading to the primary and acquired resistance to ibrutinib is essential
      for achieving better outcomes in patients with MCL. In this review, we describe
      the biology of the BCR signalling pathway and summarize the landmark clinical
      trials that have led to the approval of ibrutinib. We review the molecular
      mechanisms underlying primary and acquired ibrutinib resistance as well as recent
      studies dealing with overcoming ibrutinib resistance.

PMID- 29359798
TI  - Early minimal residual disease assessment after AML induction with fludarabine,
      cytarabine and idarubicin (FLAI) provides the most useful prognostic information.

PMID- 29359799
TI  - Identification of sphingosine kinase 1 as a therapeutic target in B-lineage acute
      lymphoblastic leukaemia.

PMID- 29359800
TI  - WT1 mRNA level reflects disease changes and progression of myelodysplastic
      syndromes patients with 'stable disease'.

PMID- 29359801
TI  - Parent-reported health-related quality of life of children with Down syndrome: a
      descriptive study.
AB  - AIM: To describe health-related quality of life of Australian children and
      adolescents with Down syndrome and compare it with norm-referenced data. METHOD:
      A cross-sectional survey was conducted with parents of 75 children and
      adolescents (43 males, 32 females) with Down syndrome aged 5 to 18 years (mean
      age 13y 2mo, SD 4y 8mo). The proxy-report KIDSCREEN-27 questionnaire was
      administered and five dimensions of health-related quality of life were measured.
      Data were analysed descriptively and compared with normative data. RESULTS: Total
      group mean scores for psychological well-being, autonomy and parent relation, and
      school environment dimensions were within normal threshold values, whereas mean
      scores for physical well-being, and social support and peers dimensions, were
      poorer. For participants with Down syndrome aged 8 to 18 years, the difference
      with normative data for proxy-reported physical well-being, psychological well
      being, and social support and peers dimensions favoured typically developing
      children. Adolescents (13-18y) with Down syndrome scored poorer on all dimensions
      than children (5-12y) with Down syndrome. INTERPRETATION: Our findings assist a
      better understanding of the lived experiences of children and adolescents with
      Down syndrome, as perceived by their parents, and suggest aspects of health that
      could be influenced to optimize their quality of life. WHAT THIS PAPER ADDS:
      Proxy-reported psychological well-being and autonomy were within the normal range
      for children with Down syndrome. Physical well-being and social support scores
      were significantly lower than normative data. Proxy-reported scores for
      adolescents with Down syndrome were consistently poorer than for children with
      Down syndrome and the differences were clinically important.

PMID- 29359803
TI  - Disruption of mammalian SWI/SNF and polycomb complexes in human sarcomas:
      mechanisms and therapeutic opportunities.
AB  - Soft-tissue sarcomas are increasingly characterized and subclassified by genetic
      abnormalities that represent underlying drivers of their pathology. Hallmark
      tumor suppressor gene mutations and pathognomonic gene fusions collectively
      account for approximately one-third of all sarcomas. These genetic abnormalities
      most often result in global transcriptional misregulation via disruption of
      protein regulatory complexes which govern chromatin architecture. Specifically,
      alterations to mammalian SWI/SNF (mSWI/SNF or BAF) ATP-dependent chromatin
      remodeling complexes and polycomb repressive complexes cause disease-specific
      changes in chromatin architecture and gene expression across a number of sarcoma
      subtypes. Understanding the functions of chromatin regulatory complexes and the
      mechanisms underpinning their roles in oncogenesis will be required for the
      design and development of new therapeutic strategies in sarcomas. Copyright (c)
      2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 29359802
TI  - Reduced orienting to audiovisual synchrony in infancy predicts autism diagnosis
      at 3 years of age.
AB  - BACKGROUND: Effective multisensory processing develops in infancy and is thought
      to be important for the perception of unified and multimodal objects and events.
      Previous research suggests impaired multisensory processing in autism, but its
      role in the early development of the disorder is yet uncertain. Here, using a
      prospective longitudinal design, we tested whether reduced visual attention to
      audiovisual synchrony is an infant marker of later-emerging autism diagnosis.
      METHODS: We studied 10-month-old siblings of children with autism using an eye
      tracking task previously used in studies of preschoolers. The task assessed the
      effect of manipulations of audiovisual synchrony on viewing patterns while the
      infants were observing point light displays of biological motion. We analyzed the
      gaze data recorded in infancy according to diagnostic status at 3 years of age
      (DSM-5). RESULTS: Ten-month-old infants who later received an autism diagnosis
      did not orient to audiovisual synchrony expressed within biological motion. In
      contrast, both infants at low-risk and high-risk siblings without autism at
      follow-up had a strong preference for this type of information. No group
      differences were observed in terms of orienting to upright biological motion.
      CONCLUSIONS: This study suggests that reduced orienting to audiovisual synchrony
      within biological motion is an early sign of autism. The findings support the
      view that poor multisensory processing could be an important antecedent marker of
      this neurodevelopmental condition.

PMID- 29359804
TI  - The effect of drought and nitrogen fertiliser addition on nitrate leaching risk
      from a pasture soil; an assessment from a field experiment and modelling.
AB  - BACKGROUND: A combination of field experiment and modelling tested the hypothesis
      that dry summers increase the risk of nitrogen (N) leaching from pasture owing to
      a combination of: soil N accumulation in a dry summer; slow recovery of drought
      affected pasture in the autumn; and the resultant inefficient use of fertiliser N
      by the pasture. RESULTS: In the experiment, pasture response to urea and apparent
      N recovery in autumn after the drought was half that of irrigated pasture (7 vs
      13 kg dry matter kg-1 N; 28 vs 52% apparent recovery; P < 0.05). There was more
      soil mineral N at the start of drainage (P < 0.001) as a result of this
      inefficient fertiliser N use. Modelling of pasture growth in six different
      drought years demonstrated that subsequent N leaching risk after rewetting was
      inversely related to pasture N uptake during rewetting in the autumn. CONCLUSION:
      When the period between post-drought pasture recovery and the onset of drainage
      is short, N leaching risk increases. Nitrogen leaching is determined by the type
      of autumn (slow or fast growing conditions before drainage) and the amount of
      fertiliser N applied. The latter can be managed by a farmer, but the former
      cannot. (c) 2018 Society of Chemical Industry.

PMID- 29359805
TI  - Biological evaluation and pharmacophore modeling of some benzoxazoles and their
      possible metabolites.
AB  - A series of benzoxazole derivatives and some possible primary metabolites were
      evaluated as anticancer agents. In vitro anti-proliferative activities of the
      compounds were tested using the SRB assay on cancerous (HeLa) and non-cancerous
      (L929) cell lines. It was found that 17 of 21 tested compounds had cytotoxic
      activity on HeLa cells and the cytotoxic activities of the compounds were 15-700
      times higher than on L929 cells. We generated two distinct pharmacophore models
      for the cytotoxic activities of the compounds on HeLa and L929 cells. While
      active compounds such as camptothecin and X8 fitted the two models generated for
      both cell lines, selective cytotoxic compounds such as XT3B fitted only the model
      generated for HeLa cells. Evaluation of the genotoxic activities of the cytotoxic
      compounds with the alkaline comet assay revealed that compounds X17 and XT3
      showed strong genotoxic effects against HeLa cells at low concentrations whereas
      they had no genotoxic effect on L929 cells. Due to the selective ability for
      inducing DNA strand breaks only on cancerous cells, the compounds were identified
      as effective derivatives for anticancer candidates.

PMID- 29359806
TI  - The role of hypoxia-inducible factors in carotid body (patho) physiology.
AB  - Hypoxia-inducible factors mediate adaptive responses to reduced O2 availability.
      In patients with obstructive sleep apnoea, repeated episodes of hypoxaemia and
      reoxygenation (intermittent hypoxia) are sensed by the carotid body (CB). The
      ensuing CB chemosensory reflex activates the sympathetic nervous system and
      increased secretion of catecholamines by the adrenal medulla, resulting in
      hypertension and breathing abnormalities. In the CB, intermittent hypoxia induces
      the formation of reactive oxygen species (ROS) and increased intracellular Ca2+
      levels, which drive increased expression of hypoxia-inducible factor (HIF) 1alpha
      and a decrease in the levels of HIF-2alpha.  Intermittent hypoxia increases HIF
      1alpha-dependent expression of Nox2, encoding the pro-oxidant enzyme NADPH
      oxidase 2, and decreased HIF-2alpha-dependent expression of Sod2, encoding the
      anti-oxidant enzyme superoxide dismutase 2. These changes in gene expression
      drive persistently elevated ROS levels in the CB, brainstem, and adrenal medulla
      that are required for the development of hypertension and breathing
      abnormalities. The ROS generated by dysregulated HIF activity in the CB results
      in oxidation and inhibition of haem oxygenase 2, and the resulting reduction in
      the levels of carbon monoxide leads to increased hydrogen sulfide production,
      triggering glomus cell depolarization. Thus, the pathophysiology of obstructive
      sleep apnoea involves the dysregulation of O2 -regulated transcription factors,
      gasotransmitters, and sympathetic outflow that affects blood pressure and
      breathing.

PMID- 29359807
TI  - Sympatholysis: the more we learn, the less we know.

PMID- 29359808
TI  - Plant genetic resources for food and agriculture: opportunities and challenges
      emerging from the science and information technology revolution.
AB  - Contents Summary 1407 I. Introduction 1408 II. Technological advances and their
      utility for gene banks and breeding, and longer-term contributions to SDGs 1408
      III. The challenges that must be overcome to realise emerging R&D opportunities
      1410 IV. Renewed governance structures for PGR (and related big data) 1413 V.
      Access and benefit sharing and big data 1416 VI. Conclusion 1417 Acknowledgements
      1417 ORCID 1417 References 1417 SUMMARY: Over the last decade, there has been an
      ongoing revolution in the exploration, manipulation and synthesis of biological
      systems, through the development of new technologies that generate, analyse and
      exploit big data. Users of Plant Genetic Resources (PGR) can potentially leverage
      these capacities to significantly increase the efficiency and effectiveness of
      their efforts to conserve, discover and utilise novel qualities in PGR, and help
      achieve the Sustainable Development Goals (SDGs). This review advances the
      discussion on these emerging opportunities and discusses how taking advantage of
      them will require data integration and synthesis across disciplinary,
      organisational and international boundaries, and the formation of multi
      disciplinary, international partnerships. We explore some of the institutional
      and policy challenges that these efforts will face, particularly how these new
      technologies may influence the structure and role of research for sustainable
      development, ownership of resources, and access and benefit sharing. We discuss
      potential responses to political and institutional challenges, ranging from
      options for enhanced structure and governance of research discovery platforms to
      internationally brokered benefit-sharing agreements, and identify a set of broad
      principles that could guide the global community as it seeks or considers
      solutions.

PMID- 29359809
TI  - Use of two-dimensional speckle tracking echocardiography to predict cardiac
      events: Comparison of patients with acute myocardial infarction and chronic
      coronary artery disease.
AB  - BACKGROUND: Two-dimensional speckle strain (2D STE) echocardiography can aid in
      the prognosis of acute myocardial infarction (AMI) and chronic coronary artery
      disease (CAD). HYPOTHESIS: Differences occur in the prediction of cardiac events
      using 2D STE in AMI vs CAD patients. METHODS: In this prospective study, 94
      patients with a first AMI and successful revascularization, and 137 patients with
      stable CAD after complete revascularization were included. In all patients, we
      performed echocardiography and myocardial deformation analysis for layer-specific
      global circumferential strain (GCS) and longitudinal strain. Receiver operating
      characteristic (ROC) curve analysis was used to predict the presence of a cardiac
      event using strain values and baseline characteristics in different regression
      models. RESULTS: Patients were followed for 3.6 +/- 0.8 years. Strain parameters
      in AMI and CAD patients were significantly different with respect to the
      occurrence of a cardiac event. Frequency of diabetes and hypertension was
      associated with the presence of a cardiac event in CAD patients. Furthermore, in
      CAD patients, ROC analysis demonstrated that the addition of endocardial GCS to
      baseline characteristics and ejection fraction to a regression model
      significantly improved the prediction of cardiac events (area under curve = 0.86,
      cutoff value: 20%, sensitivity: 79%, specificity: 84%). In contrast, the addition
      of strain parameters in AMI patients did not increase the prediction power for
      cardiac events. CONCLUSIONS: Global strain parameters by 2D STE may be useful for
      the prediction of cardiac events in patients with CAD but add no supplemental
      information to baseline characteristic and ejection fraction in patients with
      AMI.

PMID- 29359810
TI  - Ectomycorrhization of Tricholoma matsutake with Quercus aquifolioides affects the
      endophytic microbial community of host plant.
AB  - Tricholoma matsutake (S. Ito et Imai) is an ectomycorrhizal basidiomycete
      associated with Pinaceae and Fagaceae trees in the Northern Hemisphere. It is
      still unknown whether the symbiotic relationship with this ectomycorrhiza could
      affect the host plant's endophytic microbial community. In this study, we used
      high throughput sequencing to analyze the endophytic microbial communities of
      different Quercus aquifolioides tissues with or without T. matsutake partner.
      About 35,000 clean reads were obtained per sample, representing 34 bacterial
      phyla and 7 fungal phyla. We observed 3980 operational taxonomic units (OTUs) of
      bacteria and 457 OTUs of fungi at a 97% similarity level. Three bacterial phyla,
      Proteobacteria, Cyanobacteria, and Bacteroidetes, and the fungal phylum
      Ascomycota were dominant in all tissues. The relative abundance of these taxa
      differed significantly between Q. aquifolioides tissues with and without T.
      matsutake partner (p < 0.05). The bacterial genus Pseudomonas and the fungal
      genus Cryptosporiopsis were more abundant in mycorrhized roots than in control
      roots. This study showed that the community structure and dominant species of
      endophytic microbial communities in Q. aquifolioides tissues might be altered by
      colonization with T. matsutake. This work provides a new insight into the
      interactions between ectomycorrhizal fungus and host plant.

PMID- 29359811
TI  - Rubisco is not really so bad.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is the most widespread
      carboxylating enzyme in autotrophic organisms. Its kinetic and structural
      properties have been intensively studied for more than half a century. Yet
      important aspects of the catalytic mechanism remain poorly understood, especially
      the oxygenase reaction. Because of its relatively modest turnover rate (a few
      catalytic events per second) and the competitive inhibition by oxygen, Rubisco is
      often viewed as an inefficient catalyst for CO2 fixation. Considerable efforts
      have been devoted to improving its catalytic efficiency, so far without success.
      In this review, we re-examine Rubisco's catalytic performance by comparison with
      other chemically related enzymes. We find that Rubisco is not especially slow.
      Furthermore, considering both the nature and the complexity of the chemical
      reaction, its kinetic properties are unremarkable. Although not unique to
      Rubisco, oxygenation is not systematically observed in enolate and enamine
      forming enzymes and cannot be considered as an inevitable consequence of the
      mechanism. It is more likely the result of a compromise between chemical and
      metabolic imperatives. We argue that a better description of Rubisco mechanism is
      still required to better understand the link between CO2 and O2 reactivity and
      the rationale of Rubisco diversification and evolution.

PMID- 29359812
TI  - Novel insights into the disease dynamics of B-cell lymphomas in the Genomics Era.
AB  - High-throughput sequencing has significantly contributed to revealing the
      molecular underpinnings of B-cell lymphomagenesis and disease progression. It is
      now a widely accepted concept that the diversity of clinical responses to front
      line therapy and the development of relapsed/refractory disease are in part
      explained by 'inter-patient' genetic heterogeneity measurable by individual sets
      of somatic gene alterations in tumor genomes. Moreover, extensive 'intra-tumor'
      heterogeneity on the genotypic and phenotypic levels is the product of ongoing
      tumor evolution and adaptation to various selective pressures during cancer
      initiation, progression, and therapeutic intervention. As the management of
      disease progression remains one of the most significant clinical challenges, it
      is becoming increasingly important to delineate how B-cell lymphomas evolve over
      time and to develop progression-related biomarker assays. Toward this goal,
      recent investigations have moved from studying lymphoma biology at initial
      diagnosis to doing so at multiple time points during the disease course.
      Profiling progressed tumors, and in particular paired biopsies at initial
      diagnosis and disease progression of the same patients, has led to novel insights
      into clonal tumor evolution and tumor microenvironment dynamics. This review
      discusses the latest findings on genomic alterations and microenvironment biology
      associated with relapsed/refractory B-cell lymphomas, with a particular emphasis
      on alterations that are acquired or become more prevalent at disease progression.
      We also describe overarching tumor evolution patterns, and highlight emerging
      precision medicine methodologies that can aid in an improved understanding and
      management of relapsed/refractory disease. Copyright (c) 2018 Pathological
      Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29359813
TI  - Clinical and prognostic relationships of pulmonary artery to aorta diameter ratio
      in patients with heart failure: a cardiac magnetic resonance imaging study.
AB  - BACKGROUND: The pulmonary artery (PA) distends as pressure increases. HYPOTHESIS:
      The ratio of PA to aortic (Ao) diameter may be an indicator of pulmonary
      hypertension and consequently carry prognostic information in patients with
      chronic heart failure (HF). METHODS: Patients with chronic HF and control
      subjects undergoing cardiac magnetic resonance imaging were evaluated. The main
      PA diameter and the transverse axial Ao diameter at the level of bifurcation of
      the main PA were measured. The maximum diameter of both vessels was measured
      throughout the cardiac cycle and the PA/Ao ratio was calculated. RESULTS: A total
      of 384 patients (mean age, 69 years; mean left ventricular ejection fraction,
      40%; median NT-proBNP, 1010 ng/L [interquartile range, 448-2262 ng/L]) and 38
      controls were included. Controls and patients with chronic HF had similar maximum
      Ao and PA diameters and PA/Ao ratio. During a median follow-up of 1759 days
      (interquartile range, 998-2269 days), 181 patients with HF were hospitalized for
      HF or died. Neither PA diameter nor PA/Ao ratio predicted outcome in univariable
      analysis. In a multivariable model, only age and NT-proBNP were independent
      predictors of adverse events. CONCLUSIONS: The PA/Ao ratio is not a useful method
      to stratify prognosis in patients with HF.

PMID- 29359814
TI  - Resident cell lineages are preserved in pulmonary vascular remodeling.
AB  - Pulmonary vascular remodeling is the main pathological hallmark of pulmonary
      hypertension disease. We undertook a comprehensive and multilevel approach to
      investigate the origin of smooth muscle actin-expressing cells in remodeled
      vessels. Transgenic mice that allow for specific, inducible, and permanent
      labeling of endothelial (Cdh5-tdTomato), smooth muscle (Acta2-, Myh11-tdTomato),
      pericyte (Cspg4-tdTomato), and fibroblast (Pdgfra-tdTomato) lineages were used to
      delineate the cellular origins of pulmonary vascular remodeling. Mapping the fate
      of major lung resident cell types revealed smooth muscle cells (SMCs) as the
      predominant source of cells that populate remodeled pulmonary vessels in chronic
      hypoxia and allergen-induced murine models. Combining in vivo cell type-specific,
      time-controlled labeling of proliferating cells with a pulmonary artery
      phenotypic explant assay, we identified proliferation of SMCs as an underlying
      remodeling pathomechanism. Multicolor immunofluorescence analysis showed a
      preserved pattern of cell type marker localization in murine and human pulmonary
      arteries, in both donors and idiopathic pulmonary arterial hypertension (IPAH)
      patients. Whilst neural glial antigen 2 (chondroitin sulfate proteoglycan 4)
      labeled mostly vascular supportive cells with partial overlap with SMC markers,
      PDGFRalpha-expressing cells were observed in the perivascular compartment. The
      luminal vessel side was lined by a single cell layer expressing endothelial
      markers followed by an adjacent and distinct layer defined by SMC marker
      expression and pronounced thickening in remodeled vessels. Quantitative flow
      cytometric analysis of single cell digests of diverse pulmonary artery layers
      showed the preserved separation into two discrete cell populations expressing
      either endothelial cell (EC) or SMC markers in human remodeled vessels.
      Additionally, we found no evidence of overlap between EC and SMC ultrastructural
      characteristics using electron microscopy in either donor or IPAH arteries.
      Lineage-specific marker expression profiles are retained during pulmonary
      vascular remodeling without any indication of cell type conversion. The expansion
      of resident SMCs is the major underlying and evolutionarily conserved paradigm of
      pulmonary vascular disease pathogenesis. (c) 2018 The Authors. The Journal of
      Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of
      Great Britain and Ireland.

PMID- 29359815
TI  - Understanding and predicting the diffusivity of organic compounds in
      polydimethylsiloxane material for passive sampler applications using a simple
      quantitative structure-property relationship model.
AB  - The diffusivity of 145 compounds in polydimethylsiloxane (PDMS) material was
      determined in the laboratory using a film stacking technique. The results were
      pooled with available literature data, providing a final data set of 198
      compounds with diffusivity (DPDMS ) spanning over approximately 5 log units. The
      principal variables controlling the diffusivity of penetrants were investigated
      by comparing DPDMS within and between different homologous series. The dipole
      moment, molecular size, and flexibility of penetrants appear to be the most
      prevalent factors controlling a compound's diffusivity. A nonlinear quantitative
      structure-property relationship is proposed using as predicting variables the
      molecular volume, the number of rotatable bonds, the topological polar surface
      area, and the number of O and N atoms. The final relationship has a correlation
      coefficient of R2  = 0.81 and a mean absolute error of 0.26 m2 s-1 (log unit),
      approaching the average error for the experimentally determined values (0.12 m2 s
      1 ). The model, based on a heuristic approach, is ready for use by analytical
      chemists with no specific background in theoretical chemistry (notably for
      passive sampler development). Environ Toxicol Chem 2018;37:1291-1300. (c) 2018
      SETAC.

PMID- 29359816
TI  - Multitasking Ska in Chromosome Segregation: Its Distinct Pools Might Specify
      Various Functions.
AB  - The human spindle and kinetochore associated (Ska) complex is required for proper
      mitotic progression. Extensive studies have demonstrated its important functions
      in both stable kinetochore-microtubule interactions and spindle checkpoint
      silencing. We suggest a model to explain how various Ska functions might be
      fulfilled by distinct pools of Ska at kinetochores. The Ndc80-loop pool of Ska is
      recruited by the Ndc80 loop, or together with some of its flanking sequences, and
      the recruitment is also dependent on Cdk1-mediated Ska3 phosphorylation. This
      pool seems to play a more important role in silencing the spindle checkpoint than
      stabilizing kinetochore-microtubule interactions. In contrast, the Ndc80-N
      terminus pool of Ska is recruited by the N-terminal domains of Ndc80 and appears
      to be more important for stabilizing kinetochore-microtubule interactions. Here,
      we review and discuss the evidence that supports this model and suggest further
      experiments to test the functioning mechanisms of the Ska complex.

PMID- 29359817
TI  - New Layered Triazine Framework/Exfoliated 2D Polymer with Superior Sodium-Storage
      Properties.
AB  - The efficient synthesis of 2D polymers (2DPs) with tailorable structures and
      properties is highly desired but remains a considerable challenge. Here, the
      first solution synthesis of millimeter-size crystalline covalent triazine
      frameworks (CTFs) with a clear lamellar structure, which can be exfoliated into
      micrometer-size few-layer 2DP sheets via both micromechanical cleavage and liquid
      sonication, is reported. The obtained CTFs or 2DPs show a unique staggered AB
      stacking with a dominant pore size of ~0.6 nm, which is different from the common
      eclipsed AA stacking in various covalent organic frameworks. The preference for
      AB stacking is due to the specific interaction of triflic acid with CTFs as
      revealed computationally. When explored as new polymeric anodes for sodium-ion
      batteries, both crystalline bulk CTF and exfoliated 2DP exhibit very high
      capacities (225 and 262 mA h g-1 at 0.1 A g-1 , respectively), impressive rate
      capabilities (67 and 119 mA h g-1 at 5.0 A g-1 , respectively), and excellent
      cycling stability (95% capacity retention after 1200 cycles) due to their robust
      conjugated porous structure, outperforming most organic/polymeric sodium-ion
      battery anodes ever reported.

PMID- 29359818
TI  - The resolution of acyclic P-stereogenic phosphine oxides via the formation of
      diastereomeric complexes: A case study on ethyl-(2-methylphenyl)-phenylphosphine
      oxide.
AB  - As an example of acyclic P-chiral phosphine oxides, the resolution of ethyl-(2
      methylphenyl)-phenylphosphine oxide was elaborated with TADDOL derivatives, or
      with calcium salts of the tartaric acid derivatives. Besides the study on the
      resolving agents, several purification methods were developed in order to prepare
      enantiopure ethyl-(2-methylphenyl)-phenylphosphine oxide. It was found that the
      title phosphine oxide is a racemic crystal-forming compound, and the
      recrystallization of the enantiomeric mixtures could be used for the preparation
      of pure enantiomers. According to our best method, the (R)-ethyl-(2-methylphenyl)
      phenylphosphine oxide could be obtained with an enantiomeric excess of 99% and in
      a yield of 47%. Complete racemization of the enantiomerically enriched phosphine
      oxide could be accomplished via the formation of a chlorophosphonium salt.
      Characterization of the crystal structures of the enantiopure phosphine oxide was
      complemented with that of the diastereomeric intermediate. X-ray analysis
      revealed the main nonbonding interactions responsible for enantiomeric
      recognition.

PMID- 29359819
TI  - Low-Energy Electron-Induced Strand Breaks in Telomere-Derived DNA Sequences
      Influence of DNA Sequence and Topology.
AB  - During cancer radiation therapy high-energy radiation is used to reduce tumour
      tissue. The irradiation produces a shower of secondary low-energy (<20 eV)
      electrons, which are able to damage DNA very efficiently by dissociative electron
      attachment. Recently, it was suggested that low-energy electron-induced DNA
      strand breaks strongly depend on the specific DNA sequence with a high
      sensitivity of G-rich sequences. Here, we use DNA origami platforms to expose G
      rich telomere sequences to low-energy (8.8 eV) electrons to determine absolute
      cross sections for strand breakage and to study the influence of sequence
      modifications and topology of telomeric DNA on the strand breakage. We find that
      the telomeric DNA 5'-(TTA GGG)2 is more sensitive to low-energy electrons than an
      intermixed sequence 5'-(TGT GTG A)2 confirming the unique electronic properties
      resulting from G-stacking. With increasing length of the oligonucleotide (i.e.,
      going from 5'-(GGG ATT)2 to 5'-(GGG ATT)4 ), both the variety of topology and the
      electron-induced strand break cross sections increase. Addition of K+ ions
      decreases the strand break cross section for all sequences that are able to fold
      G-quadruplexes or G-intermediates, whereas the strand break cross section for the
      intermixed sequence remains unchanged. These results indicate that telomeric DNA
      is rather sensitive towards low-energy electron-induced strand breakage
      suggesting significant telomere shortening that can also occur during cancer
      radiation therapy.

PMID- 29359820
TI  - Terahertz Emission from Hybrid Perovskites Driven by Ultrafast Charge Separation
      and Strong Electron-Phonon Coupling.
AB  - Unusual photophysical properties of organic-inorganic hybrid perovskites have not
      only enabled exceptional performance in optoelectronic devices, but also led to
      debates on the nature of charge carriers in these materials. This study makes the
      first observation of intense terahertz (THz) emission from the hybrid perovskite
      methylammonium lead iodide (CH3 NH3 PbI3 ) following photoexcitation, enabling an
      ultrafast probe of charge separation, hot-carrier transport, and carrier-lattice
      coupling under 1-sun-equivalent illumination conditions. Using this approach, the
      initial charge separation/transport in the hybrid perovskites is shown to be
      driven by diffusion and not by surface fields or intrinsic ferroelectricity.
      Diffusivities of the hot and band-edge carriers along the surface normal
      direction are calculated by analyzing the emitted THz transients, with direct
      implications for hot-carrier device applications. Furthermore, photogenerated
      carriers are found to drive coherent terahertz-frequency lattice distortions,
      associated with reorganizations of the lead-iodide octahedra as well as coupled
      vibrations of the organic and inorganic sublattices. This strong and coherent
      carrier-lattice coupling is resolved on femtosecond timescales and found to be
      important both for resonant and far-above-gap photoexcitation. This study
      indicates that ultrafast lattice distortions play a key role in the initial
      processes associated with charge transport.

PMID- 29359821
TI  - Biofunctionalized "Kiwifruit-Assembly" of Oxidoreductases in Mesoporous
      ZnO/Carbon Nanoparticles for Efficient Asymmetric Catalysis.
AB  - A mesoporous ZnO/carbon composite is designed for coimmobilization of two
      oxidoreductases involving a novel "kiwifruit-assembly" pattern. The
      coimmobilization of (S)-carbonyl reductase II-glucose dehydrogenase on
      nanoparticles (SCRII-GDHnano ) exhibits 40-50% higher specific activity than the
      free enzyme and significantly improves stabilities of enzymes to heat, pH and
      solvents. It performs asymmetric catalysis of 75 * 10-3 m substrate with a
      perfect yield of 100% and an excellent enantioselectivity of 99.9% within 1 h.
      SCRII-GDHnano gives an over 72% yield and 99.9% enantioselectivity after it is
      reused for ten times. Even with a highly concentrated (400 * 10-3 m) substrate,
      it shows about 60% yield and 99.9% enantioselectivity within 4 h. SCRII-GDHnano
      presents 4.5-8.0-fold higher productivity in 2.0-8.0-fold shorter reaction time
      than the free enzyme. This work provides a general, facile, and unique approach
      for the immobilization of two oxidoreductases and gives high catalytic
      efficiency, long-term and good recycling stabilities by triggering radical proton
      coupled electron transfer.

PMID- 29359822
TI  - Switch-ON Near IR Fluorescent Dye Upon Protonation: Helically Twisted Bis(Boron
      Difluoride) Complex of pi-Extended Corrorin.
AB  - A novel helically twisted pi-extended corrorin derivative having two boron
      dipyrrin (BODIPY) moieties at the periphery, a BODIPY DYEmer (6-BF2 ) cross
      bridged with pi-conjugated dipyrrinylidene unit, was synthesized and
      characterized. The neutral 6-BF2 is nonfluorescent due to the internal
      photoinduced charge transfer (CT) character in the excited state as inferred from
      the femtosecond transient absorption spectroscopy. However, upon protonation, the
      CT process is suppressed and the species H6-BF2+ becomes near infrared (IR)
      emissive. With the aid of rigid helical conformations in 6-BF2 , the helical
      isomers (P- and M-forms) were resolved and their chiroptical property was
      investigated. The distinct circular dichroism (CD) spectral changes of the
      enantiomers were observed in the presence of acids, which demonstrates that 6-BF2
      can be utilized for potential acid-responsive chiroptical materials.

PMID- 29359823
TI  - Detection and characterization of colitis-associated cancer/dysplasia: Based on
      reports from the JDDW 2017 and meta-analyses of prospective studies concerning
      endoscopic procedure.

PMID- 29359824
TI  - Evidence of Nitrogen Contribution to the Electronic Structure of the CH3 NH3 PbI3
      Perovskite.
AB  - Despite fast development of hybrid perovskite solar cells, there are many
      fundamental questions related to the perovskite film which remain open. For
      example, there are contradicting theoretical reports on the role of the organic
      methylammonium cation (CH3 NH3+ ) in the methylammonium lead triiodide (CH3 NH3
      PbI3 ) perovskite film. From one side it is reported that the organic cation does
      not contribute to electronic structure of the CH3 NH3 PbI3 film. From the other
      side, valence band maximum fluctuations, dependent on the CH3 NH3+ rotation, have
      been theoretically predicted. The resonant X-ray photoelectron spectroscopy
      results reported here show experimental evidence of nitrogen contribution to the
      CH3 NH3 PbI3 electronic structure. Moreover, the observed strong resonances of
      nitrogen with the I 5s and the Pb 5d-6s levels indicate that the CH3 NH3 PbI3
      valence band is extended up to ~18 eV below the Fermi energy, and therefore one
      should also consider these shallow core levels while modeling its electronic
      structure.

PMID- 29359825
TI  - Architected Lattices with High Stiffness and Toughness via Multicore-Shell 3D
      Printing.
AB  - The ability to create architected materials that possess both high stiffness and
      toughness remains an elusive goal, since these properties are often mutually
      exclusive. Natural materials, such as bone, overcome such limitations by
      combining different toughening mechanisms across multiple length scales. Here, a
      new method for creating architected lattices composed of core-shell struts that
      are both stiff and tough is reported. Specifically, these lattices contain
      orthotropic struts with flexible epoxy core-brittle epoxy shell motifs in the
      absence and presence of an elastomeric silicone interfacial layer, which are
      fabricated by a multicore-shell, 3D printing technique. It is found that
      architected lattices produced with a flexible core-elastomeric interface-brittle
      shell motif exhibit both high stiffness and toughness.

PMID- 29359826
TI  - Cosensitized Quantum Dot Solar Cells with Conversion Efficiency over 12.
AB  - The improvement of sunlight utilization is a fundamental approach for the
      construction of high-efficiency quantum-dot-based solar cells (QDSCs). To boost
      light harvesting, cosensitized photoanodes are fabricated in this work by a
      sequential deposition of presynthesized Zn-Cu-In-Se (ZCISe) and CdSe quantum dots
      (QDs) on mesoporous TiO2 films via the control of the interactions between QDs
      and TiO2 films using 3-mercaptopropionic acid bifunctional linkers. By the
      synergistic effect of ZCISe-alloyed QDs with a wide light absorption range and
      CdSe QDs with a high extinction coefficient, the incident photon-to-electron
      conversion efficiency is significantly improved over single QD-based QDSCs. It is
      found that the performance of cosensitized photoanodes can be optimized by
      adjusting the size of CdSe QDs introduced. In combination with titanium mesh
      supported mesoporous carbon as a counterelectrode and a modified polysulfide
      solution as an electrolyte, a champion power conversion efficiency up to 12.75%
      (Voc = 0.752 V, Jsc = 27.39 mA cm-2 , FF = 0.619) is achieved, which is, as far
      as it is known, the highest efficiency for liquid-junction QD-based solar cells
      reported.

PMID- 29359827
TI  - Functional Materials and Systems for Rewritable Paper.
AB  - "Paper" has greatly contributed to the development and spread of civilization.
      Even in today's "digitalized" world, paper continues to play a key role in
      socioeconomic growth, as is evidenced by the growth in global paper consumption.
      Unfortunately, the use of paper has its cost in terms of the exhaustion of
      world's natural resources. Consequently, new, cost-effective technologies that
      preserve natural resources are required for this purpose. Functional materials
      have revolutionized the way people think about developing new technologies.
      Especially important in this regard are "smart reactive materials," which are
      capable of actively responding to external stimuli such as heat, light,
      mechanical stress, and specific molecular orientations. Moreover, functionalized
      chromogenic materials, which undergo reversible color switching upon external
      stimulation, have attracted great attention in the context of developing
      rewritable paper. Here, investigations of various materials and systems that are
      devised for use as rewritable paper are reviewed with the hope that the coverage
      will stimulate and guide future studies in this area.

PMID- 29359828
TI  - Nestin expression and in vivo proliferative potential of tanycytes and ependymal
      cells lining the walls of the third ventricle in the adult rat brain.
AB  - There is a disagreement in the literature concerning the degree of proliferation
      of cells in the walls of the third ventricle (3rdV) under normal conditions in
      the adult mammalian brain. To address this issue, we mapped the cells expressing
      the neural stem/progenitor cell marker nestin along the entire rostrocaudal
      extent of the 3rdV in adult male rats and observed a complex distribution.
      Abundant nestin was present in tanycyte cell bodies and processes and also was
      observed in patches of ependymal cells as well as in isolated ependymal cells
      throughout the walls of the 3rdV. However, we observed very limited ependymal
      cell or tanycyte proliferation in normal adult rats as determined by
      bromodeoxyuridine (BrdU) incorporation or the expression of Ki-67. Moreover,
      fewer than 13% of the cells that were BrdU-positive (BrdU+) or Ki-67-positive (Ki
      67+) expressed nestin. These observations stand in contrast to those made in the
      subventricular zone of the lateral ventricle (SVZ) and subgranular zone of the
      hippocampal formation (SGZ), where cell proliferation measured by BrdU
      incorporation or Ki-67 expression is observed frequently in cells that also
      express nestin. Thus, while ependymal cell or tanycyte cell proliferation can be
      promoted by the addition of mitogens, dietary modifications or other in vivo
      manipulations, the proliferation of ependymal cells and tanycytes in the walls of
      the 3rdV is very limited in the normal adult male rat brain.

PMID- 29359829
TI  - Highly Durable and Active Pt-Based Nanoscale Design for Fuel-Cell Oxygen
      Reduction Electrocatalysts.
AB  - Fuel cells are one of the promising energy-conversion devices due to their high
      efficiency and zero emission. Although recent advances in electrocatalysts have
      been achieved using various material designs such as alloys, core@shell
      structures, and shape control, many issues still remain to be resolved.
      Especially, material design issues for high durability and high activity are
      recently accentuated owing to severe instability of nanoparticles under fuel-cell
      operating conditions. To address these issues, fundamental understanding of
      functional links between activity and durability is timely urgent. Here, the
      activity and durability of nanoscale materials are summarized, focusing on the
      nanoparticle size effect. In addition to phenomenological observation, two major
      degradation origins, including atomic dissolution and particle size increase, are
      discussed related to the activity decrease. Based on the fundamental
      understanding of nanoparticle degradation, recent promising strategies for
      durable Pt-based nanoscale electrocatalysts are introduced and the role of each
      design for durability enhancement is discussed. Finally, short comments related
      to the future direction of nanoparticle issues are provided in terms of
      nanoparticle synthesis and analysis.

PMID- 29359830
TI  - Integrated anatomical and physiological mapping of striatal afferent projections.
AB  - The dorsomedial striatum, a key site of reward-sensitive motor output, receives
      extensive afferent input from cortex, thalamus and midbrain. These projections
      are integrated by striatal microcircuits containing both spiny projection neurons
      and local circuit interneurons. To explore target cell specificity of these
      projections, we compared inputs onto D1-dopamine receptor-positive spiny neurons,
      parvalbumin-positive fast-spiking interneurons and somatostatin-positive low
      threshold-spiking interneurons, using cell type-specific rabies virus tracing and
      optogenetic-mediated projection neuron recruitment in mice. While the relative
      proportion of retrogradely labelled projection neurons was similar between target
      cell types, the convergence of inputs was systematically higher for projections
      onto fast-spiking interneurons. Rabies virus is frequently used to assess cell
      specific anatomical connectivity but it is unclear how this correlates to
      synaptic connectivity and efficacy. To test this, we compared tracing data with
      target cell-specific measures of synaptic efficacy for anterior cingulate cortex
      and parafascicular thalamic projections using novel quantitative optogenetic
      measures. We found that target-specific patterns of convergence were extensively
      modified according to region of projection neuron origin and postsynaptic cell
      type. Furthermore, we observed significant divergence between cell type-specific
      anatomical connectivity and measures of excitatory synaptic strength,
      particularly for low-threshold-spiking interneurons. Taken together, this
      suggests a basic uniform connectivity map for striatal afferent inputs upon which
      presynaptic-postsynaptic interactions impose substantial diversity of
      physiological connectivity.

PMID- 29359832
TI  - A Highly Reversible Mechanochromic Difluorobenzothiadiazole Dye with Near
      Infrared Emission.
AB  - A difluorobenzothiadiazole-based fluorescent material with a D-pi-A-pi-D
      structure exhibits a reversible mechanofluorochromic characteristic in the solid
      state. Its red fluorescent emission switches to near-infrared fluorescence upon
      mechanical stimulation, but recover after fuming the ground solid powder with
      dichloromethane.

PMID- 29359831
TI  - Behavioural and neural sequelae of stressor exposure are not modulated by
      controllability in females.
AB  - The degree of behavioural control that an organism has over a stressor is a
      potent modulator of the stressor's impact; controllable stressors produce none of
      the neurochemical and behavioural sequelae that occur if the stressor is
      uncontrollable. Research demonstrating the importance of control and the neural
      mechanisms responsible has been conducted almost entirely with male rats. It is
      unknown if behavioural control is stress blunting in females, and whether or not
      a similar resilience circuitry is engaged. Female rats were exposed to
      controllable, yoked uncontrollable or no tailshock. In separate experiments,
      behavioural (juvenile social exploration, fear and shuttle box escape) and
      neurochemical (activation of dorsal raphe serotonin and dorsal raphe-projecting
      prelimbic neurons) outcomes, which are sensitive to the dimension of control in
      males, were assessed. Despite successful acquisition of the controlling response,
      behavioural control did not mitigate dorsal raphe serotonergic activation and
      behavioural outcomes induced by tailshock, as it does in males. Moreover,
      behavioural control failed to selectively engage prelimbic cells that project to
      the dorsal raphe as in males. Pharmacological activation of the prelimbic cortex
      restored the stress-buffering effects of control. Collectively, the data
      demonstrate stressor controllability phenomena are absent in females and that the
      protective prelimbic circuitry is present but not engaged. Reduced benefit from
      coping responses may represent a novel approach for understanding differential
      sex prevalence in stress-related psychiatric disorders.

PMID- 29359833
TI  - Functional connectivity maps based on hippocampal and thalamic dynamics may
      account for the default-mode network.
AB  - The default-mode network (DMN) has been reported to comprise a set of inter
      connected transmodal cortical areas, including the posterior cingulate cortex
      (PCC), medial prefrontal cortex, posterior inferior parietal lobule, lateral
      temporal region and others. However, the subcortical constituents of the DMN are
      still not clear. This study aimed to examine whether the correlation maps derived
      from subcortical structures may also account for neural pattern of the DMN.
      Structural magnetic resonance imaging (MRI) and resting-state functional MRI
      scans of 36 subjects were selected from the Rockland sample (Nathan Kline
      Institute). The hippocampus and thalamus were chosen as subcortical regions of
      interest (ROIs). Each ROI was partitioned into composite modules which in turn
      provided simplified and representative dynamics of blood-oxygen-level-dependent
      (BOLD) signals. PCC-seeded and ROI-based correlation maps were compared by
      conjunction analyses and paired t-tests (corrected P < 0.05). Our results
      unveiled that the hippocampus-, thalamus- and PCC-centred correlation patterns
      actually overlapped to a substantial degree. Integrating the signals in the
      thalamus and hippocampus altogether fully explained the PCC-seeded DMN.
      Supplementary analyses based on the BOLD dynamics in several subcortical nuclei
      (caudate, putamen and globus pallidus) were dissimilar to the DMN. The DMN
      derived from the ROI/seed-based approach may represent combined limbic and region
      specific informatics (and their closely interacting neural substrates). The
      possible causes for previous methods of task-induced deactivation and seed-based
      correlation that failed to depict the holistic limbic picture are discussed. The
      neocortical manifestation of DMN may reflect the limbic information in the
      transmodal brain regions.

PMID- 29359834
TI  - Tuberculosis after liver transplantation in a large center in New York City:
      QuantiFERON(r) -TB Gold-based pre-transplant screening performance and active
      tuberculosis post-transplant.
AB  - INTRODUCTION: Pre-transplant screening for latent tuberculosis infection (LTBI)
      is a complex consideration that varies by institution. Inconsistent performance
      of interferon-gamma release assay (IGRA) further complicates screening. Data
      regarding LTBI screening outcomes and test characteristics in a large, foreign
      born pre-transplant population within the United States are limited. METHODS: In
      this retrospective study, patients who received QuantiFERON(r) -TB Gold (QFT)
      prior to liver transplantation (LT) were included. Characteristics of patients
      were compared by QFT result, and predictors of indeterminate results were
      evaluated. Similar comparisons were performed between patients who developed
      active TB and those who did not. RESULTS: Of 148 patients screened, the rate of
      positive, indeterminate, and negative testing was 13.5% (20/148), 27% (40/148),
      and 59% (88/148), respectively. An indeterminate QFT result was more than 16
      times more likely in patients with a Model for End-stage Liver Disease score >25
      (odds ratio [OR] 16.7; 95% confidence interval [CI], 2.1-132.0; P = .008) and
      more than 4 times when performed in our institution's lab compared with
      commercial lab (OR 4.1; 95% CI, 1.34-12.44; P = .013). The overall TB incidence
      was 1102/100 000 transplant cases. No patient who developed active TB had a
      positive QFT. All were born outside of the United States (P = .06) and had pre
      transplantation chest imaging demonstrating granulomatous disease (P = .006).
      CONCLUSION: Our experience further highlights the challenges of LTBI screening
      prior to LT and suggests that QFT may be a poor predictor of active TB in higher
      risk pre-transplant populations. Candidates should be screened as early as
      possible to optimize QFT performance, and local epidemiological data should be
      used to create institution-specific screening protocols in areas with large
      populations from TB-endemic regions. Management should consider TB risk factors,
      QFT, and imaging instead of reliance on QFT testing alone.

PMID- 29359835
TI  - Synergistic N-Heterocyclic Carbene/Palladium-Catalyzed Reactions of Aldehyde Acyl
      Anions with either Diarylmethyl or Allylic Carbonates.
AB  - Benzylation and allylation of aldehyde acyl anions were enabled by the merger of
      a thiazolium N-heterocyclic carbene (NHC) catalyst and a palladium/bisphosphine
      catalyst in a synergistic manner. Owing to the mildness of the reaction
      conditions, various functional groups were tolerated in the substrates.

PMID- 29359836
TI  - Factors and outcomes in association with sepsis differ between simultaneous
      pancreas/kidney and single kidney transplant recipients.
AB  - BACKGROUND: As immunosuppressive therapy has improved in simultaneous
      pancreas/kidney transplant recipients (SPKTRs), infection has become the major
      limitation of disease-free survival. METHODS: We studied all SPKTRs and deceased
      donor kidney transplant recipients (KTRs) between 2003 and 2015. Thirty-six of
      134 SPKTRs (26.9%) were diagnosed with sepsis among which 13/36 SPKTRs (36.1%)
      developed severe sepsis/septic shock. A control group of 98 SPKTRs without sepsis
      and 61/538 KTRs (11.3%) with sepsis were used for comparison. RESULTS: Among
      SPKTRs, female sex, low BMI, CMV seronegativity, CMV disease, and acute cellular
      rejection increased the risk for sepsis (P < .05). Patient and allograft survival
      was comparable among SPKTRs with and without sepsis (P > .05), but showed
      inferior kidney allograft function (P < .05). While urosepsis was less common
      among SPKTRs (45%), pneumonia (33%) and peritonitis (15%) as site of infections
      were more frequent (P < .05). Here, gram-positive and fungal sepsis were more
      common among SPKTRs compared to KTRs (P < .05). SPKTRs showed a higher incidence
      and an earlier onset of sepsis compared to KTRs (P < .001). SPKTRs with severe
      sepsis/septic shock were more likely to show pneumonia as site of infection with
      gram-positive/polymicrobial bacteremia (P < .05). Mortality from severe sepsis
      was 29% among SPKTRs compared to 58% among KTRs (P < .05). CONCLUSION:
      Differences in incidence, site, causative pathogens, and onset of sepsis between
      SPKTRs and KTRs may be attributed to more intense immunosuppression, major
      surgery, and complications of diabetes among SPKTRs. Lower sepsis-related
      mortality may reflect younger age and more timely diagnosis, but also supports
      recent findings of less sepsis-related mortality among recipients of solid organ
      transplantation.

PMID- 29359837
TI  - A cluster of donor-derived Cryptococcus neoformans infection affecting lung,
      liver, and kidney transplant recipients: Case report and review of literature.
AB  - Donor-derived infections (DDIs) are a very rare but potentially devastating
      complication of solid organ transplantation. Here we present a cluster of proven
      donor-derived cryptococcal infection in the kidney, liver, and lung recipients
      from a single donor. Remarkably, the onset of illness in the kidney and liver
      recipients occurred more than 8-12 weeks after transplantation, which is beyond
      the incubation period previously reported for donor-derived cryptococcosis. DDI
      should always be considered in the differential diagnosis of transplant
      recipients admitted with febrile illness, even when presenting beyond the first
      month post-transplant. Communication between reference laboratories, transplant
      centers, and organ procurement organizations is critical to improve outcomes.

PMID- 29359838
TI  - Discrimination between the endoplasmic reticulum and mitochondria by
      spontaneously inserting tail-anchored proteins.
AB  - Tail-anchored (TA) proteins insert into their target organelles by incompletely
      elucidated posttranslational pathways. Some TA proteins spontaneously insert into
      protein-free liposomes, yet target a specific organelle in vivo. Two
      spontaneously inserting cytochrome b5 forms, b5-ER and b5-RR, which differ only
      in the charge of the C-terminal region, target the endoplasmic reticulum (ER) or
      the mitochondrial outer membrane (MOM), respectively. To bridge the gap between
      the cell-free and in cellula results, we analyzed targeting in digitonin
      permeabilized adherent HeLa cells. In the absence of cytosol, the MOM was the
      destination of both b5 forms, whereas in cytosol the C-terminal negative charge
      of b5-ER determined targeting to the ER. Inhibition of the transmembrane
      recognition complex (TRC) pathway only partially reduced b5 targeting, while
      strongly affecting the classical TRC substrate synaptobrevin 2 (Syb2). To
      identify additional pathways, we tested a number of small inhibitors, and found
      that Eeyarestatin I (ESI ) reduced insertion of b5-ER and of another
      spontaneously inserting TA protein, while not affecting Syb2. The effect was
      independent from the known targets of ESI , Sec61 and p97/VCP. Our results
      demonstrate that the MOM is the preferred destination of spontaneously inserting
      TA proteins, regardless of their C-terminal charge, and reveal a novel, substrate
      specific ER-targeting pathway.

PMID- 29359839
TI  - Long-term follow-up of post renal transplantation Epstein-Barr virus-associated
      smooth muscle tumors: Report of two cases and review of the literature.
AB  - Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) following solid
      organ transplantation are very rare slow growing neoplasms. Most tumors present
      with non-specific symptoms mainly related to tumor location. Post-transplant EBV
      associated small muscle tumors have been reported in various anatomical
      locations. The tumors have a predilection to unusual sites for SMTs and tend to
      be multifocal. The histologic appearance of these tumors generally does not
      predict their clinical behavior. Surgery and reduction in immunosuppression are
      the main stays of management. We herein report two cases of post renal transplant
      EBV-associated SMTs with over 6 years of follow-up. A 33-year-old male patient
      presented with hepatic lesions and a 49-year-old female patient presented with
      multiple mesenteric and gluteal lesions. The tumors were diagnosed 6 and 10 years
      after renal transplantation, respectively. Surgical resection and
      reduction/discontinuation of immunosuppression were successful in delaying
      progression of the disease; however, in both cases, the allografts failed during
      the course of management.

PMID- 29359840
TI  - Highly Fluorescent Chiral N-S-Doped Carbon Dots from Cysteine: Affecting Cellular
      Energy Metabolism.
AB  - Cysteine-based chiral optically active carbon dots (CDs) and their effects on
      cellular energy metabolism, which is vital for essential cellular functions, have
      been barely reported. A green and effective synthesis strategy for chiral N-S
      doped CDs (fluorescence quantum yield ca. 41.26 %) based on hydrothermal
      treatment of l- or d-cysteine at as low as 60  degrees C has been developed. This
      suggested that cysteine was instable in aqueous solutions and acts as a warning
      for high-temperature synthesis of nanomaterials using cysteine as stabilizer.
      Human bladder cancer T24 cells treated with l-CDs showed up-regulated glycolysis,
      while d-CDs had no similar effects. In contrast, no disturbance to the basal
      mitochondrial aerobic respiration of T24 cells was caused by either chiral CD.

PMID- 29359841
TI  - Autologous hematopoietic stem cell transplant in a patient with leprosy: Is it
      safe?
AB  - A patient with non-Hodgkin lymphoma, preparing for an autologous hematopoietic
      stem cell transplant (HSCT), developed leprosy. The patient was successfully
      treated with rifampicin, ofloxacin, and doxycycline, and the HSCT was performed
      without complications, being the first report, to our knowledge, of leprosy in an
      autologous HSCT patient.

PMID- 29359842
TI  - Carbapenem-resistant Klebsiella pneumoniae vertebral osteomyelitis in a renal
      transplant recipient treated with ceftazidime-avibactam.
AB  - Ceftazidime-avibactam (CAZ-AVI) is a novel cephalosporin beta lactamase inhibitor
      combination that has shown activity against carbapenem-resistant
      Enterobactericeae. Data are limited on its utilization in the treatment of
      carbapenem-resistant Klebsiella pneumoniae osteomyelitis in solid organ
      transplant patients. We describe a case report on the use of CAZ-AVI in the
      treatment of vertebral osteomyelitis in a renal transplant recipient.

PMID- 29359843
TI  - Norovirus causing severe gastrointestinal disease following allogeneic
      hematopoietic stem cell transplantation: A retrospective analysis.
AB  - BACKGROUND: Norovirus (NV) can cause chronic and severe gastroenteritis with
      possible lethal outcome in immunocompromised patients. The knowledge of NV
      infections in allogeneic hematopoietic stem cell transplantation (HSCT)
      recipients is limited. The aim of this study was to clarify the clinical
      importance of NV in a large cohort of HSCT recipients. METHODS: All patients
      undergoing HSCT and diagnosed with NV at Karolinska University Hospital from 2006
      2012 were included in the study (63 patients). Clinical data were collected from
      medical records, and statistics were performed using the logistic regression
      method. RESULTS: The majority of patients (70%) had short-term symptoms (<=14
      days). However, 54% of all patients required admission or prolonged
      hospitalization owing to the infection. In 16% of the patients the symptoms were
      chronic (>30 days), and in all but one of these patients the clinical picture
      also was severe, with malnutrition requiring long-term TPN, or serious
      dehydration. Severe combined immune deficiency (SCID) diagnosis was associated
      with chronic symptoms of NV infection (OR 30.3, CI 2.5-368). CONCLUSION: NV is an
      important pathogen in the HSCT setting, although the infection seems to be mild
      in most patients. Increased knowledge is needed to further identify risk factors
      for a severe course of NV infection in HSCT patients.

PMID- 29359844
TI  - Hepatitis A, cardiomyopathy, aplastic anemia, and acute liver failure: A
      devastating scenario.
AB  - Hepatitis A virus (HAV) causes an acute infection and is usually asymptomatic in
      children. When clinical manifestations appear, these include choluria, jaundice,
      and abdominal pain. Although infrequent, extra-hepatic manifestations related to
      HAV have been described, affecting the heart, bone marrow, blood vessels, and
      other tissues.A 10-year-old boy from a rural area presented with a 15-day history
      of malaise, fever, and jaundice; laboratory examinations were compatible with HAV
      infection. The patient turned encephalopathic and was remitted to our center,
      where laboratory examinations showed a medullary aplasia and fulminant hepatitis
      requiring a liver transplant that was performed 72 hours after admission. At 24
      hours post transplant, the patient developed a cardiomyopathy secondary to HAV,
      and intravenous immunoglobulin was administered. The patient is still alive and
      attending his medical check-ups.Although rare, extra-hepatic manifestations of
      HAV infection have been described in 14% of cases. The groups of patients
      affected are usually aged and present with high bilirubin levels. Acquired
      aplastic anemia and myocarditis caused by HAV are uncommon, and its
      pathophysiology has not yet been elucidated.HAV infection is usually asymptomatic
      in children, although extra-hepatic manifestations can appear requiring early
      detection and management.

PMID- 29359845
TI  - Acanthamoeba endophthalmitis during treatment for cutaneous disease in a renal
      transplant patient.
AB  - Acanthamoeba infections are difficult to diagnose and treat. We present a renal
      transplant patient who developed Acanthamoeba endophthalmitis on therapy with
      posaconazole and miltefosine for cutaneous acanthamobiasis. The patient was
      maintained on intracameral voriconazole injections, and oral azithromycin,
      fluconazole, and flucytosine. This case highlights novel presentations and
      treatments for acanthamoebic infection.

PMID- 29359846
TI  - Progressive multifocal leukoencephalopathy after T-cell replete HLA
      haploidentical transplantation with post-transplantation cyclophosphamide graft
      versus-host disease prophylaxis.
AB  - A 52-year-old man suffered from progressive multifocal leukoencephalopathy (PML)
      after human leukocyte antigen (HLA)-haploidentical transplantation with post
      transplantation cyclophosphamide (PTCY). Mirtazapine, mefloquine, and cytarabine
      failed to improve his symptoms, and he finally died 4.5 months after PML onset.
      This is the first case report of a patient with PML after HLA-haploidentical
      transplantation with PTCY. Although T-cell replete HLA-haploidentical
      transplantation with PTCY has enabled early immune reconstitution, PML should be
      considered if a patient's mental condition deteriorates.

PMID- 29359847
TI  - Successful resolution of hyperammonemia following hematopoietic cell
      transplantation with directed treatment of Ureaplasma parvum infection.
AB  - Hyperammonemia following hematopoietic cell transplantation (HCT) has been
      characterized as idiopathic and is associated with a very high mortality. A
      causal relationship between Ureaplasma infection and hyperammonemia in
      immunocompromised lung transplant recipients has recently been described. We
      document the first case of hyperammonemia following HCT associated with
      Ureaplasma parvum. The initiation of appropriate antibiotics resulted in rapid
      resolution of hyperammonemic encephalopathy and eradication of the implicating
      organism.

PMID- 29359848
TI  - Optimizing the management of hypoglycaemia in individuals with type 2 diabetes: A
      randomized crossover comparison of a weight-based protocol compared with two
      fixed-dose glucose regimens.
AB  - AIMS: To determine whether an individualized body weight-based glucose treatment
      in adults with type 2 diabetes (T2DM) is more likely to resolve hypoglycaemia
      with a single treatment without excessive rebound hyperglycaemia compared to
      fixed doses of 12 or 30 g of glucose. METHODS: Adults with T2DM were enrolled in
      a cross-over study. Each episode of hypoglycaemia (capillary glucose <4.0 mmol/L)
      was randomly assigned to 1 of 3 treatment protocols: 0.3 g glucose/kg body-weight
      or a fixed dose of either 12 or 30 g glucose, independent of weight. All
      participants received each treatment in random order for up to 15 hypoglycaemic
      episodes. Glucose was re-tested 10 minutes after treatment, with a repeat dose if
      still <4 mmol/L. RESULTS: Mean (SD) age of the 30 participants was 68 (8.1)
      years, mean weight was 91.5 (16.8) kg and mean HbA1c was 58.7 (9.2) mmol/mol.
      Among a total of 244 episodes of hypoglycaemia, 10 participants had 15 treatment
      episodes and 18 participants had fewer than 10 treatment episodes. The odds
      ratio, adjusted for multiple comparisons, for resolution of hypoglycaemia at 10
      minutes, comparing weight-based treatment and 12 g treatment was 3.2 (95% CI, 1.1
      9.0), P = .009, comparing 30 g treatment and 12 g treatment was 8.9 (95% CI, 2.2
      36.6), P < .001, and comparing weight-based treatment and 30 g treatment was 0.36
      (95% CI, 0.08-1.67) P = .10. CONCLUSION: In T2DM, both a weight-based 0.3 g/kg
      treatment and a fixed 30 g glucose treatment result in higher blood glucose than
      a 12 g treatment, along with increased probability of resolution of hypoglycaemia
      after 10 minutes. Both treatments result in an excess of mild rebound
      hyperglycaemia (>8 mmol/L) at 30 minutes.

PMID- 29359849
TI  - Antibiotic exposure in early life and childhood overweight and obesity: A
      systematic review and meta-analysis.
AB  - We conducted a systematic review and meta-analysis of observational studies
      investigating the association between antibiotic exposure in infancy and risk of
      childhood overweight and obesity. Thirteen studies, including a total of 527 504
      children, were included in the systematic review and 8 were included in meta
      analyses. Exposure to antibiotics in infancy was associated with an increased
      odds ratio (OR) of childhood overweight and obesity (OR 1.11, 95% confidence
      interval [CI] 1.02-1.20). Whereas exposure to 1 treatment only and exposure
      between 6 and 24 months were not associated with increased risk of childhood
      overweight and obesity, exposure to >1 treatment was associated with an OR of
      1.24 (95% CI 1.09-1.43) and exposure within the first 6 months of life was
      associated with an OR of 1.20 (95% CI 1.04-1.37). In conclusion, antibiotic
      exposure in infancy was associated with a slightly increased risk of childhood
      overweight and obesity, mainly if children were exposed to repeated treatments or
      treatment within the first 6 months of life. It is unclear whether this
      association is mediated via direct effects of antibiotics on the gut microbiota.

PMID- 29359850
TI  - Bioorthogonal Catalytic Activation of Platinum and Ruthenium Anticancer Complexes
      by FAD and Flavoproteins.
AB  - Recent advances in bioorthogonal catalysis promise to deliver new chemical tools
      for performing chemoselective transformations in complex biological environments.
      Herein, we report how FAD (flavin adenine dinucleotide), FMN (flavin
      mononucleotide), and four flavoproteins act as unconventional photocatalysts
      capable of converting PtIV and RuII complexes into potentially toxic PtII or RuII
      -OH2 species. In the presence of electron donors and low doses of visible light,
      the flavoproteins mini singlet oxygen generator (miniSOG) and NADH oxidase (NOX)
      catalytically activate PtIV prodrugs with bioorthogonal selectivity. In the
      presence of NADH, NOX catalyzes PtIV activation in the dark as well, indicating
      for the first time that flavoenzymes may contribute to initiating the activity of
      PtIV chemotherapeutic agents.

PMID- 29359851
TI  - Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a
      preserved ejection fraction by counterbalancing the effects of leptin? A novel
      hypothesis.
AB  - Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious
      heart failure events in patients with type 2 diabetes, but little is known about
      mechanisms that might mediate this benefit. The most common heart failure
      phenotype in type 2 diabetes is obesity-related heart failure with a preserved
      ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin
      in this disorder leads to sodium retention and plasma volume expansion as well as
      to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated
      neurohormonal activation appears to enhance the expression of SGLT2 in the renal
      tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular
      sites in a manner that can oppose the sodium retention produced by leptin. In
      addition, SGLT2 inhibitors reduce the accumulation and inflammation of
      perivisceral adipose tissue, thus minimizing the secretion of leptin and its
      paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis
      probably contributes to the impairment of cardiac distensibility and glomerular
      function that characterizes obesity-related HFpEF. Ongoing clinical trials with
      SGLT2 inhibitors in heart failure are positioned to confirm or refute the
      hypothesis that these drugs may favourably influence the course of obesity
      related HFpEF by their ability to attenuate the secretion and actions of leptin.

PMID- 29359852
TI  - Glass and Alchemy in Early Modern Europe: An Analytical Study of Glassware from
      the Oberstockstall Laboratory in Austria.
AB  - Glass distillation equipment from an early modern alchemical laboratory was
      analyzed for its technology of manufacture and potential origin. Chemical data
      show that the assemblage can be divided into sodium-rich, colorless distillation
      vessels made with glass from Venice or its European imitation, and potassium-rich
      dark-brown non-specialized forms produced within the technological tradition of
      forest glass typical for central and north-western Europe. These results complete
      our understanding of the supply of technical apparatus at one of the best
      preserved alchemical laboratories and highlight an early awareness of the need
      for high-quality instruments to guarantee the successful outcome of specialized
      chemical operations. This study demonstrates the potential of archaeological
      science to inform historical research around the practice of early chemistry and
      the development of modern science.

PMID- 29359853
TI  - Prolonged in vivo functional assessment of the mouse oviduct using optical
      coherence tomography through a dorsal imaging window.
AB  - The oviduct (or fallopian tube) serves as an environment for gamete transport,
      fertilization and preimplantation embryo development in mammals. Although there
      has been increasing evidence linking infertility with disrupted oviduct function,
      the specific roles that the oviduct plays in both normal and impaired
      reproductive processes remain unclear. The mouse is an important mammalian model
      to study human reproduction. However, most of the current analyses of the mouse
      oviduct rely on static histology or 2D visualization, and are unable to provide
      dynamic and volumetric characterization of this organ. The lack of imaging access
      prevents longitudinal live analysis of the oviduct and its associated
      reproductive events, limiting the understanding of mechanistic aspects of
      fertilization and preimplantation pregnancy. To address this limitation, we
      report a 3D imaging approach that enables prolonged functional assessment of the
      mouse oviduct in vivo. By combining optical coherence tomography with a dorsal
      imaging window, this method allows for extended volumetric visualization of the
      oviduct dynamics, which was previously not achievable. The approach is used for
      quantitative analysis of oviduct contraction, spatiotemporal characterization of
      cilia beat frequency and longitudinal imaging. This new approach is a useful in
      vivo imaging platform for a variety of live studies in mammalian reproduction.

PMID- 29359855
TI  - Descemet membrane endothelial keratoplasty developing spontaneous 'malignant
      glaucoma' secondary to gas misdirection.

PMID- 29359854
TI  - Clinical features, BTD gene mutations, and their functional studies of eight
      symptomatic patients with biotinidase deficiency from Southern China.
AB  - Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disease,
      which develops neurological and cutaneous symptoms because of the impaired biotin
      recycling. Pathogenic mutations on BTD gene cause BTD deficiency. Clinical
      features and mutation analysis of Chinese children with BTD deficiency were
      rarely described. Herein, for the first time, we reported the clinical features,
      BTD gene mutations and their functional studies of eight symptomatic children
      with BTD deficiency from southern China. Fatigue, hypotonia, proximal muscular
      weakness, hearing deficits, rash and respiratory problems are common clinical
      phenotype of our patients. Seizures are observed only in patients with profound
      BTD deficiency. Five novel mutations were detected, among which c.637delC
      (H213TfsTer51) was found in 50% of our patients and might be considered as a
      common mutation. In vitro studies confirmed three mild mutations c.1368A>C
      (Q456H), c.1613G>A (R538H), and c.644T>A (L215H) which retained 10-30% of wild
      type enzyme activity, and six severe mutations c.235C>T (R79C), c.1271G>C
      (C424S), c.1412G>A (C471Y), c.637delC (H213TfsTer51), c.395T>G (M132W), c.464T>C
      (L155P), and c.1493dupT (L498FfsTer13) which retained <10% of wild type enzyme
      activity. c.1330G>C (D444H) decreased the protein expression but not activity of
      BTD enzyme, and H213TfsTer51 was structurally damaging while L498FfsTer13 was
      functionally damaging. These results will be helpful in establishing the
      definitive diagnosis of BTD deficiency at the gene level, offering appropriate
      genetic counseling, and providing clues to structure/function relationships of
      the enzyme.

PMID- 29359856
TI  - Efficacy and safety of flumazenil injection for the reversal of midazolam
      sedation after elective outpatient endoscopy.
AB  - OBJECTIVE: Midazolam sedation during elective endoscopy is widely performed and
      flumazenil is frequently administered after endoscopy to reverse sedation in
      clinical practice. This study aimed to investigate the safety and efficacy of
      flumazenil injections after elective endoscopy under midazolam sedation. METHODS:
      Participants who underwent an upper endoscopy under midazolam sedation were
      randomly divided into two groups. In group I, flumazenil was administered i.v. 10
      min after the patient's transfer to the recovery room, and no antidote was
      injected in group II. The time of stay in the recovery room and adverse events
      were reviewed through the nursing records. We asked the patients about their pain
      and degree of satisfaction according to a visual analogue scale (VAS), their
      memory of the procedure, mental status and the presence of uncomfortable symptoms
      on the day of the procedure and the day afterwards. RESULTS: The length of stay
      in recovery was significantly shorter in group I than in group II. No significant
      differences were found in the number of patients with pain (VAS >=1), adverse
      events and discomfort between the two groups. Additionally, there were no
      differences in the patients' memory of the procedure, satisfaction with sedation,
      willingness to repeat the endoscopy and mental status. CONCLUSIONS: The time in
      the recovery room after flumazenil administration was significantly shortened,
      and the use of the drug did not increase the risk of adverse events or
      discomfort. The use of flumazenil for reversing midazolam sedation seems to be
      safe and effective.

PMID- 29359857
TI  - Proteome Profile of American Hybrid Grape cv. Blanc du Bois during Ripening
      Reveals Proteins Associated with Flavor Volatiles and Ethylene Production.
AB  - The study of key control points in ripening is essential to improve grape wine
      quality. Molecular basis of ripening is still far from being understood from the
      Pierce's disease (PD)-tolerant grapes predominantly grown in the southeastern
      United States. To identify proteins expressed during Blanc du Bois grape berry
      green and ripening stages, proteome analysis from five different stages revealed
      1091, 1131, 1078, 1042, and 1066 proteins. Differential expression analysis
      revealed 551 common proteins across different stages of maturity that are
      involved in various biochemical and metabolic pathways. The proteins identified
      were associated with phenylpropanoids, isoquinoline alkaloids, fatty acids,
      unsaturated fatty acids, and furanones. Our data provide the first step to
      understand the complex biochemical changes during ripening of PD-tolerant
      American hybrid grapes that are popular for their aroma and flavor profile in the
      southeastern United States. Proteomics data are deposited to the ProteomeXchange
      PXD004157.

PMID- 29359858
TI  - 2DE Gels: A Story of Love and Hate in Proteomics.

PMID- 29359860
TI  - Using Titer and Titer Normalized to Confluence Are Complementary Strategies for
      Obtaining Chinese Hamster Ovary Cell Lines with High Volumetric Productivity of
      Etanercept.
AB  - The selection of clonally derived Chinese hamster ovary (CHO) cell lines with the
      highest production rate of recombinant glycoproteins remains a big challenge
      during early stages of cell line development. Different strategies using either
      product titer or product titer normalized to cell number are being used to assess
      suspension-adapted clones when grown statically in microtiter plates. However, no
      reported study so far has performed a direct head-to-head comparison of these two
      early reporters for predicting clone performance. Therefore, a screening platform
      for high-throughput analysis of titer and confluence of etanercept-producing
      clones is developed. Then an unbiased comparison of clone ranking based on either
      titer or titer normalized to confluence (TTC) is performed. Using two different
      suspension cultivation vessels, the authors demonstrate that titer- or TTC-based
      ranking gives rise to the selection of clones with similar volumetric
      productivity in batch cultures. Therefore, using both titer- and TTC-based
      ranking is proposed, allowing for selection of distinct clones with both high
      integral of viable cell density (IVCD) and high specific productivity features,
      respectively. This contributes to selection of a versatile panel of clones that
      can be further characterized and from which the final producer clone can be
      selected that best fits the production requirements.

PMID- 29359861
TI  - Silk-Based Bioinks for 3D Bioprinting.
AB  - 3D bioprinting field is making remarkable progress; however, the development of
      critical sized engineered tissue construct is still a farfetched goal. Silk
      fibroin offers a promising choice for bioink material. Nature has imparted
      several unique structural features in silk protein to ensure spinnability by
      silkworms or spider. Researchers have modified the structure-property
      relationship by reverse engineering to further improve shear thinning behavior,
      high printability, cytocompatible gelation, and high structural fidelity. In this
      review, it is attempted to summarize the recent advancements made in the field of
      3D bioprinting in context of two major sources of silk fibroin: silkworm silk and
      spider silk (native and recombinant). The challenges faced by current approaches
      in processing silk bioinks, cellular signaling pathways modulated by silk
      chemistry and secondary conformations, gaps in knowledge, and future directions
      acquired for pushing the field further toward clinic are further elaborated.

PMID- 29359862
TI  - Obesity does not influence prostate intrafractional motion.
AB  - INTRODUCTION: Motion of the prostate is problematic in the accurate delivery of
      external beam radiation therapy (EBRT) for prostate cancer. This study
      investigated the relationship between body mass index (BMI), an easily measured
      indicator of obesity, and prostate motion. METHODS: Prostate motion during EBRT
      was assessed by measuring the displacement of fiducial markers implanted within
      the prostate in 130 prostate cancer patients. Interfractional motion was
      corrected on daily imaging through pre-treatment cone-beam-computed tomography
      (CBCT) and intrafractional motion measured using movie sequences captured using
      an electronic portal imaging device (EPID) during treatment delivery. RESULTS:
      There was no statistically significant relationship between the mean
      intrafractional motion and BMI, except in the left-right (LR) translation (P =
      0.049) over the study population. For each BMI category, there was no statistical
      significance (P > 0.05) between any of the translations/rotations except LR (P =
      0.003). CONCLUSION: While intrafractional motion is an important consideration,
      prostate motion cannot be reliably predicted through measurement of patient's
      BMI.

PMID- 29359863
TI  - Dose and Timing of N-Cadherin Mimetic Peptides Regulate MSC Chondrogenesis within
      Hydrogels.
AB  - The transmembrane glycoprotein N-cadherin (NCad) mediates cell-cell interactions
      found during mesenchymal condensation and chondrogenesis. Here, NCad-derived
      peptides (i.e., HAV) are incorporated into hyaluronic acid (HA) hydrogels with
      encapsulated mesenchymal stem cells (MSCs). Since the dose and timing of NCad
      signaling are dynamic, HAV peptide presentation is tuned via alterations in
      peptide concentration and incorporation of an ADAM10-cleavable domain between the
      hydrogel and the HAV motif, respectively. HA hydrogels functionalized with HAV
      result in dose-dependent increases in early chondrogenesis of encapsulated MSCs
      and resultant cartilage matrix production. For example, type II collagen and
      glycosaminoglycan production increase ~9- and 2-fold with the highest dose of HAV
      (i.e., 2 * 10-3 m), respectively, when compared to unmodified hydrogels, while
      incorporation of an efficient ADAM10-cleavable domain between the HAV peptide and
      hydrogel abolishes increases in chondrogenesis and matrix production. Treatment
      with a small-molecule ADAM10 inhibitor restores the functional effect of the HAV
      peptide, indicating that timing and duration of HAV peptide presentation is
      crucial for robust chondrogenesis. This study demonstrates a nuanced approach to
      the biofunctionalization of hydrogels to better emulate the complex cell
      microenvironment during embryogenesis toward stem-cell-based cartilage
      production.

PMID- 29359864
TI  - Bifunctional Oxygen Reduction/Oxygen Evolution Activity of Mixed Fe/Co Oxide
      Nanoparticles with Variable Fe/Co Ratios Supported on Multiwalled Carbon
      Nanotubes.
AB  - A facile strategy is reported for the synthesis of Fe/Co mixed metal oxide
      nanoparticles supported on, and embedded inside, high purity oxidized multiwalled
      carbon nanotubes (MWCNTs) of narrow diameter distribution as effective
      bifunctional catalysts able to reversibly drive the oxygen evolution reaction
      (OER) and the oxygen reduction reaction (ORR) in alkaline solutions. Variation of
      the Fe/Co ratio resulted in a pronounced trend in the bifunctional ORR/OER
      activity. Controlled synthesis and in-depth characterization enabled the
      identification of an optimal Fe/Co composition, which afforded a low OER/OER
      reversible overvoltage of only 0.831 V, taking the OER at 10 mA cm-2 and the ORR
      at -1 mA cm-2 . Importantly, the optimal catalyst with a Fe/Co ratio of 2:3
      exhibited very promising long-term stability with no evident change in the
      potential for both the ORR and the OER after 400 charge/discharge (OER/ORR)
      cycles at 15 mA cm-2 in 6 m KOH. Moreover, detailed investigation of the
      structure, size, and phase composition of the mixed Fe/Co oxide nanoparticles, as
      well as their localization (inside of or on the surface of the MWCNTs) revealed
      insight of the possible contribution of the individual catalyst components and
      their synergistic interaction in the catalysis.

PMID- 29359866
TI  - Soy Protein/Cellulose Nanofiber Scaffolds Mimicking Skin Extracellular Matrix for
      Enhanced Wound Healing.
AB  - Historically, soy protein and extracts have been used extensively in foods due to
      their high protein and mineral content. More recently, soy protein has received
      attention for a variety of its potential health benefits, including enhanced skin
      regeneration. It has been reported that soy protein possesses bioactive molecules
      similar to extracellular matrix (ECM) proteins and estrogen. In wound healing,
      oral and topical soy has been heralded as a safe and cost-effective alternative
      to animal protein and endogenous estrogen. However, engineering soy protein-based
      fibrous dressings, while recapitulating ECM microenvironment and maintaining a
      moist environment, remains a challenge. Here, the development of an entirely
      plant-based nanofibrous dressing comprised of cellulose acetate (CA) and soy
      protein hydrolysate (SPH) using rotary jet spinning is described. The spun
      nanofibers successfully mimic physicochemical properties of the native skin ECM
      and exhibit a high water retaining capability. In vitro, CA/SPH nanofibers
      promote fibroblast proliferation, migration, infiltration, and integrin beta1
      expression. In vivo, CA/SPH scaffolds accelerate re-epithelialization and
      epidermal thinning as well as reduce scar formation and collagen anisotropy in a
      similar fashion to other fibrous scaffolds, but without the use of animal
      proteins or synthetic polymers. These results affirm the potential of CA/SPH
      nanofibers as a novel wound dressing.

PMID- 29359867
TI  - Early infections in the intensive care unit after liver transplantation-etiology
      and risk factors: A single-center experience.
AB  - BACKGROUND: Infectious complications represent one of the main causes of
      perioperative morbidity and mortality of liver transplant recipients. The primary
      objective of this retrospective observational study was to evaluate incidence and
      etiology of early (within 1 month from surgery and occurring in the intensive
      care unit [ICU]) postoperative infections as well as donor- and recipient-related
      risk factors. METHODS: The data of 280 patients undergoing 299 consecutive liver
      transplant procedures from January 2012 to December 2015 were extracted from the
      Italian ICU registry database and hospital registries. Perioperative risk
      factors, etiology of infections, and antibiotic susceptibility of isolated
      microorganisms were taken into consideration. RESULTS: Global incidence of
      postoperative infections was 21%. Pneumonia was the most frequent infection and,
      globally, gram-negative bacteria were the most common agents. Septic shock was
      present in 22% of infection cases and hospital mortality was higher in patients
      with postoperative infection. Preoperative chronic obstructive pulmonary disease,
      malnutrition, preoperative ascites, encephalopathy, and early re-transplantation
      were significantly associated to post orthotopic LT infections. CONCLUSION:
      Infections represent a major cause of early postoperative morbidity and
      mortality. The impact of single risk factors and the results of their
      preoperative management should be further investigated in order to reduce the
      incidence and evolution of postoperative infections.

PMID- 29359868
TI  - Personalized subcutaneous administration of hepatitis B surface antibodies
      without nucleos(t)ide analogs for patients at risk of renal failure after liver
      transplantation: a prospective single center cohort study.
AB  - Currently, nucleos(t)ide analogs (NAs) in monotherapy are favored as prophylaxis
      against hepatitis B recurrence after liver transplantation. However, in patients
      at risk of renal failure, renal safety of NAs is of concern. We investigated the
      safety and efficacy of subcutaneous (SC) hepatitis B immunoglobulins (HBIG) in
      monotherapy. This is a single-arm prospective trial in patients transplanted >1
      year. We included 43 Caucasian patients. The majority was treated with
      calcineurin inhibitors, and several patients had other risk factors for renal
      impairment as well: diabetes mellitus (n = 10/43), arterial hypertension (n =
      11/43), and hyperlipidemia (=10/43). At inclusion, 42% (n = 18) had chronic
      kidney disease >= grade 3a. All patients were switched from IV HBIG with or
      without NAs to SC HBIG without NAs. After one year, the targeted titer was
      lowered to >=150 IU/l in patients with low risk of recurrence. Mean follow-up
      time was 36 +/- 5 months. None of the patients had a relapse of HBsAg or HBV DNA.
      The treatment was well tolerated, safe and the renal function remained unchanged
      both in patients with (n = 18) or without (n = 25) renal impairment at baseline.
      The mean HBsAb titer could be decreased from 343 +/- 163 to 199 +/- 81 IU/l in
      the low-risk group (n = 17) and 218 +/- 71 IU/l in the high-risk group (n = 26).
      In 86% (n = 37) doses, reductions were possible, which significantly lowered the
      cost of treatment. SC HBIG without NAs had a 100% success rate in the long-term
      prevention of HBsAg and HBV DNA reappearance, without deterioration of renal
      function.

PMID- 29359869
TI  - Erratum.

PMID- 29359870
TI  - Breakthrough Exophiala dermatitidis infection during prophylactic administration
      of micafungin during second umbilical cord blood transplantation after graft
      failure.
AB  - Exophiala dermatitidis infections in patients with hematological malignancies are
      very rare. Our patient had a blood stream infection caused by E. dermatitidis
      following the second umbilical cord blood transplantation (UCBT) after graft
      failure during the first UCBT. To our knowledge, this is the first report
      describing a breakthrough fungal infection caused by E. dermatitidis during the
      prophylactic administration of micafungin (MCFG). Therefore, MCFG-treated
      patients should be monitored for breakthrough E. dermatitidis infection during
      hematopoietic stem cell transplantation.

PMID- 29359871
TI  - Association between the time after transplantation and different
      immunosuppressive medications with dental and periodontal treatment need in
      patients after solid organ transplantation.
AB  - OBJECTIVE: The aim of this study was to investigate the association of time after
      transplantation and different immunosuppressive medications with dental and
      periodontal treatment needs in patients after solid organ transplantation (SOT).
      METHODS: After lung, liver, or kidney transplantation, patients were included and
      divided into subgroups based on the time after SOT (0-1, 1-3, 3-6, 6-10, and >10
      years) and immunosuppression (tacrolimus, cyclosporine, mycophenolate,
      glucocorticoids, sirolimus, and monotherapy vs combination). Dental treatment
      need was determined by the presence of carious lesions, while periodontal
      treatment need was diagnosed based on a Periodontal Screening index score of 3-4.
      The overall treatment need included both the dental and/or periodontal treatment
      needs. Statistical analysis was performed using the Kruskal-Wallis test and chi
      squared test (P < .05). RESULTS: A total of 169 patients were included after SOT.
      A dental treatment need of 44%, a periodontal treatment need of 71%, and an
      overall treatment need of 84% were detected in the total cohort. Only patients
      with >10 years after SOT had a lower dental treatment need compared to the other
      groups (P = .02). All other comparisons of dental, periodontal, and overall
      treatment needs were comparable between subgroups depending on time since SOT.
      Furthermore, no statistically significant differences were found in terms of the
      dental, periodontal, or overall treatment needs following the administration of
      different immunosuppressive medications. CONCLUSION: The high treatment need of
      patients after SOT, irrespective of the time since transplantation, suggests
      insufficient dental and periodontal treatment before and maintenance after organ
      transplantation. Furthermore, immunosuppressive medication was not associated
      with the treatment need.

PMID- 29359872
TI  - Mycobacterium abscessus infections in lung transplant recipients: 15-year
      experience from a single institution.
AB  - PURPOSE: To evaluate our institutional experience with Mycobacterium abscessus
      infections occurring in lung transplant recipients (LTR). METHODS: We
      retrospectively reviewed our prospectively collected institutional adult lung
      transplant database from 2001 to 2015 to identify patients with M. abscessus or
      Mycobacterium chelonae/abscessus infection before or after transplantation.
      Untreated, colonized patients were excluded from the study. Electronic health
      records of nine out of 516 lung recipients (1.74%) with clinical infection were
      reviewed to determine outcomes. RESULTS: Seven patients acquired the infection
      after transplantation. Indications for transplantation were: idiopathic pulmonary
      fibrosis (in 6), chronic obstructive pulmonary disease (in 2), and cystic
      fibrosis (in 1). Five patients (55.5%) underwent bilateral lung transplantation;
      one patient required bilateral re-transplantation for complications from
      infection. M. abscessus was isolated from the respiratory tract with a median
      time of 7.5 months (range: 3 days to 13 months) from transplantation. All
      patients were treated using a multidrug regimen, with durations ranging from 3
      days to 12 months. Complications from infection included death in one patient,
      bronchial anastomotic dehiscence in one patient, delayed bronchial occlusions in
      two patients, and osteomyelitis of the knee in one patient. Median survival time
      from transplantation was 39 months (range: 11-96 months) and from the date of
      first positive culture was 58 months (range: 3-91 months). Five patients (55.5%)
      were cured but two had re-infections >1 year later. CONCLUSIONS: Mycobacterium
      abscessus infection in LTR is rare and can lead to severe complications.
      Eradication is difficult and usually requires prolonged combination antibiotic
      therapy and occasionally surgical management.

PMID- 29359874
TI  - Fusion map: A useful tool to guide ablation in oblique accessory pathways.

PMID- 29359873
TI  - Predicting age from cortical structure across the lifespan.
AB  - Despite interindividual differences in cortical structure, cross-sectional and
      longitudinal studies have demonstrated a large degree of population-level
      consistency in age-related differences in brain morphology. This study assessed
      how accurately an individual's age could be predicted by estimates of cortical
      morphology, comparing a variety of structural measures, including thickness,
      gyrification and fractal dimensionality. Structural measures were calculated
      across up to seven different parcellation approaches, ranging from one region to
      1000 regions. The age prediction framework was trained using morphological
      measures obtained from T1-weighted MRI volumes collected from multiple sites,
      yielding a training dataset of 1056 healthy adults, aged 18-97. Age predictions
      were calculated using a machine-learning approach that incorporated nonlinear
      differences over the lifespan. In two independent, held-out test samples, age
      predictions had a median error of 6-7 years. Age predictions were best when using
      a combination of cortical metrics, both thickness and fractal dimensionality.
      Overall, the results reveal that age-related differences in brain structure are
      systematic enough to enable reliable age prediction based on metrics of cortical
      morphology.

PMID- 29359875
TI  - Pain in severe dementia: A comparison of a fine-grained assessment approach to an
      observational checklist designed for clinical settings.
AB  - BACKGROUND: Fine-grained observational approaches to pain assessment (e.g. the
      Facial Action Coding System; FACS) are used to evaluate pain in individuals with
      and without dementia. These approaches are difficult to utilize in clinical
      settings as they require specialized training and equipment. Easy-to-use
      observational approaches (e.g. the Pain Assessment Checklist for Limited Ability
      to Communicate-II; PACSLAC-II) have been developed for clinical settings. Our
      goal was to compare a FACS-based fine-grained system to the PACSLAC-II in
      differentiating painful from non-painful states in older adults with and without
      dementia. METHOD: We video-recorded older long-term care residents with dementia
      and older adult outpatients without dementia, during a quiet baseline condition
      and while they took part in a physiotherapy examination designed to identify
      painful areas. Videos were coded using pain-related behaviours from the FACS and
      the PACSLAC-II. RESULTS: Both tools differentiated between painful and non
      painful states, but the PACSLAC-II accounted for more variance than the FACS
      based approach. Participants with dementia scored higher on the PACSLAC-II than
      participants without dementia. CONCLUSION: The results suggest that easy-to-use
      observational approaches for clinical settings are valid and that there may not
      be any clinically important advantages to using more resource-intensive coding
      approaches based on FACS. We acknowledge, as a limitation of our study, that we
      used as baseline a quiet condition that did not involve significant patient
      movement. In contrast, our pain condition involved systematic patient movement.
      Future research should be aimed at replicating our results using a baseline
      condition that involves non-painful movements. SIGNIFICANCE: Examining older
      adults with and without dementia, a brief observational clinical approach was
      found to be valid and accounted for more variance in differentiating pain-related
      and non-pain-related states than did a detailed time-consuming fine-grained
      approach.

PMID- 29359877
TI  - A genomic map of clinal variation across the European rabbit hybrid zone.
AB  - Speciation is a process proceeding from weak to complete reproductive isolation.
      In this continuum, naturally hybridizing taxa provide a promising avenue for
      revealing the genetic changes associated with the incipient stages of speciation.
      To identify such changes between two subspecies of rabbits that display partial
      reproductive isolation, we studied patterns of allele frequency change across
      their hybrid zone using whole-genome sequencing. To connect levels and patterns
      of genetic differentiation with phenotypic manifestations of subfertility in
      hybrid rabbits, we further investigated patterns of gene expression in testis.
      Geographic cline analysis revealed 253 regions characterized by steep changes in
      allele frequency across their natural region of contact. This catalog of regions
      is likely to be enriched for loci implicated in reproductive barriers and yielded
      several insights into the evolution of hybrid dysfunction in rabbits: (i)
      incomplete reproductive isolation is likely governed by the effects of many loci,
      (ii) protein-protein interaction analysis suggest that genes within these loci
      interact more than expected by chance, (iii) regulatory variation is likely the
      primary driver of incompatibilities, and (iv) large chromosomal rearrangements
      appear not to be a major mechanism underlying incompatibilities or promoting
      isolation in the face of gene flow. We detected extensive misregulation of gene
      expression in testis of hybrid males, but not a statistical overrepresentation of
      differentially expressed genes in candidate regions. Our results also did not
      support an X chromosome-wide disruption of expression as observed in mice and
      cats, suggesting variation in the mechanistic basis of hybrid male reduced
      fertility among mammals.

PMID- 29359876
TI  - A successful aggressive surgical and medical approach to pulmonary artery
      obstruction due to Mycobacterium abscessus infection post lung transplantation.
AB  - Mycobacterium abscessus infection following lung transplantation has historically
      been associated with poor outcomes. We report a case of bilateral lung
      retransplantation complicated by obstruction of the right pulmonary artery
      secondary to M. abscessus mycotic aneurysm. Aggressive surgical management,
      including reconstruction of the right pulmonary artery, was undertaken with
      prolonged antimicrobial therapy. Thirty-six months later, antibiotics have been
      discontinued and the patient has stable soft tissue chest wall disease with good
      graft function. Mortality and morbidity associated with M. abscessus infection is
      considerable but this case illustrates that with aggressive early management,
      outcomes may be favorable.

PMID- 29359878
TI  - Where Should You Publish? Choosing a Journal for Your Manuscript.

PMID- 29359879
TI  - Considerations for Implementing Group-Level Prenatal Health Interventions in Low
      Resource Communities: Lessons Learned From Haiti.
AB  - Haiti's high maternal and infant mortality rates evidence an urgent need for
      implementation of evidence-based strategies. A potential cost-effective strategy
      to mitigate high maternal and infant mortality rates is group prenatal care, an
      innovative model that combines antenatal clinical assessment with pregnancy
      education. Despite research demonstrating the effectiveness of this model in high
      resource settings, less is known about the challenges of implementing it in low
      resource settings. The purpose of this article is to provide recommendations for
      overcoming challenges of implementing group prenatal care in low-resources
      communities globally. Challenges addressed include language, literacy, space,
      cultural appropriateness of intervention content, and sociopolitical climate.
      Using examples from work conducted in Haiti, this information can be used to
      assist practitioners and researchers with overcoming challenges of implementing
      models of group care in international low-resource communities.

PMID- 29359880
TI  - Longitudinal analysis on the effect of insertion torque on delayed single
      implants: A 3-year randomized clinical study.
AB  - BACKGROUND: Implant stability is commonly related to insertion torque. Recently,
      it has been suggested that higher insertion torque may lead to greater bone
      resorption. PURPOSE: The aim of the present randomized clinical study was to
      evaluate the role of different insertion torque values in terms of implant
      success, marginal bone loss, and facial soft tissues recession. MATERIALS AND
      METHODS: Patients requiring a single dental implant were recruited and randomized
      to receive one of two implants with the same macro-geometry but different cutting
      designs. First group consists of a 90 degrees cutting groove know as self-tapping
      implant, and the second group known as BlossomTM cutting groove. (Intra-Lock,
      Boca Raton, Florida). The insertion torque (IT) was assessed and two groups
      followed: high-IT (>=50 Ncm) group and regular-IT (<50 Ncm) group. After 3
      months, all the implants were restored. At baseline, buccal bone thickness (BBT)
      was recorded. During the 3-year survey, the following outcomes had been
      registered: implant failures and success, radiographic marginal bone level around
      dental implant (MBL) and facial soft tissue level (FSTL). RESULTS: A hundred and
      sixteen implants were placed in healed sites. The overall survival rate after 3
      years was 96.5%. The Cumulative Success Rate was 91.3% for the High IT group and
      98.2% for the Regular IT group. The mean marginal bone loss and facial soft
      tissue recession, at a 3-year evaluation, were significantly greater for the High
      IT group and in the mandible than that reached in the Regular-IT group and in the
      maxilla. CONCLUSION: Present findings showed that implants placed with higher
      insertion torque in mandible led to greater bone resorption and mucosal recession
      than that registered for implants placed with a regular IT. Moreover, sites with
      a thick buccal bone wall (>=1 mm) showed smaller recession at the facial soft
      tissue level after 3 years.

PMID- 29359881
TI  - 3-Year follow-up of temporary implantable nitinol device implantation for the
      treatment of benign prostatic obstruction.
AB  - OBJECTIVES: To report 3-year follow-up results of the first implantations with a
      temporary implantable nitinol device (TIND(r) ; Medi-Tate Ltd., Or Akiva, Israel)
      for the treatment of lower urinary tract symptoms (LUTS) secondary to benign
      prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 32 patients with LUTS
      were enrolled in this prospective study. The study was approved by the local
      Ethics Committee. Inclusion criteria were: age >50 years, International Prostate
      Symptom Score (IPSS) >=10, peak urinary flow (Qmax ) <12 mL/s, and prostate
      volume <60 mL. The TIND was implanted within the bladder neck and the prostatic
      urethra under light sedation, and removed 5 days later in an outpatient setting.
      Demographics, perioperative results, complications (according to Clavien-Dindo
      classification), functional results, and quality of life (QoL) were evaluated.
      Follow-up assessments were made at 3 and 6 weeks, and 3, 6, 12, 24 and 36 months
      after the implantation. The Student's t-test, one-way analysis of variance and
      Kruskal-Wallis tests were used for statistical analyses. RESULTS: At baseline,
      the mean (standard deviation, sd) patient age was 69.4 (8.2) years, prostate
      volume was 29.5 (7.4) mL, and Qmax was 7.6 (2.2) mL/s. The median (interquartile
      range, IQR) IPSS was 19 (14-23) and the QoL score was 3 (3-4). All the
      implantations were successful, with a mean total operative time of 5.8 min. No
      intraoperative complications were recorded. The change from baseline in IPSS, QoL
      score and Qmax was significant at every follow-up time point. After 36 months of
      follow-up, a 41% rise in Qmax was achieved (mean 10.1 mL/s), the median (IQR)
      IPSS was 12 (6-24) and the IPSS QoL was 2 (1-4). Four early complications (12.5%)
      were recorded, including one case of urinary retention (3.1%), one case of
      transient incontinence due to device displacement (3.1%), and two cases of
      infection (6.2%). No further complications were recorded during the 36-month
      follow-up. CONCLUSIONS: The extended follow-up period corroborated our previous
      findings and suggests that TIND implantation is safe, effective and well
      tolerated, for at least 36 months after treatment.

PMID- 29359882
TI  - Open radical cystectomy in England: the current standard of care - an analysis of
      the British Association of Urological Surgeons (BAUS) cystectomy audit and
      Hospital Episodes Statistics (HES) data.
AB  - OBJECTIVE: To establish the current standard for open radical cystectomy (ORC) in
      England, as data entry by surgeons performing RC to the British Association of
      Urological Surgeons (BAUS) database was mandated in 2013 and combining this with
      Hospital Episodes Statistics (HES) data has allowed comprehensive outcome
      analysis for the first time. PATIENTS AND METHODS: All patients were included in
      this analysis if they were uploaded to the BAUS data registry and reported to
      have been performed in the 2 years between 1 January 2014 and 31 December 2015 in
      England (from mandate onwards) and had been documented as being performed in an
      open fashion (not laparoscopic, robot assisted or the technique field left
      blank). The HES data were accessed via the HES website. Office of Population
      Censuses and Surveys Classification of Surgical Operations and Procedures version
      4 (OPCS-4) Code M34 was searched during the same 2-year time frame (not including
      M34.4 for simple cystectomy or with additional minimal access codes Y75.1-9
      documenting a laparoscopic or robotic approach was used) to assess data capture.
      RESULTS: A total of 2 537 ORCs were recorded in the BAUS registry and 3 043 in
      the HES data. This indicates a capture rate of 83.4% of all cases. The median
      operative time was 5 h, harvesting a median of 11-20 lymph nodes, with a median
      blood loss of 500-1 000 mL, and a transfusion rate of 21.8%. The median length of
      stay was 11 days, with a 30-day mortality rate of 1.58%. CONCLUSIONS: This is the
      largest, contemporary cohort of ORCs in England, encompassing >80% of all
      performed operations. We now know the current standard for ORC in England. This
      provides the basis for individual surgeons and units to compare their outcomes
      and a standard with which future techniques and modifications can be compared.

PMID- 29359883
TI  - A clinician-centred programme for behaviour change in the optimal use of staging
      investigations for newly diagnosed prostate cancer.
AB  - OBJECTIVES: To improve imaging utilisation and reduce the widespread overuse of
      staging investigations, in the form of computed tomography (CT) and whole-body
      bone scans for men with newly diagnosed prostate cancer in the Hunter region of
      NSW, Australia, by implementation of a multifaceted clinician-centred behaviour
      change programme. PATIENTS AND METHODS: Records of all patients with a new
      diagnosis of prostate cancer were reviewed prior to the intervention (July 2014
      to July 2015), and the results of this audit were presented to participating
      urologists by a clinical champion. Urologists then underwent focused education
      based on current guidelines. Patterns of imaging use for staging were then re
      evaluated (November 2015 to July 2016). Patients were stratified into low-,
      intermediate- and high-risk groups as described by the D'Amico classification
      system. RESULTS: A total of 144 patients were retrospectively enrolled into the
      study cohort. The use of diagnostic imaging for staging purposes significantly
      decreased in men with low- and intermediate-risk disease post intervention. In
      low-risk patients, the use of CT decreased from 43% to 0% (P = 0.01). A total of
      21% of patients underwent bone scans in the pre-intervention group compared
      with18% in the post-intervention group (P = 0.84). In intermediate-risk patients,
      the use of CT decreased from 89% to 34% (P < 0.001), whilst the use of bone scan
      decreased from 63% to 37% (P = 0.02). In high-risk patients, the appropriate use
      of imaging was maintained, with CT performed in 87% compared with 85% and bone
      scan in 87% compared with 65% (P = 0.07). CONCLUSION: Our results show that a
      focused, clinician-centred education programme can lead to improved guideline
      adherence at a regional level. The assessment of trends and application of such a
      programme at a state-based or national level could be further assessed in the
      future with the help of registry data. This will be particularly important in
      future with the advent of advanced imaging, such as prostate-specific membrane
      antigen positron-emission tomography.

PMID- 29359885
TI  - Mechano-Based Transductive Sensing for Wearable Healthcare.
AB  - Wearable healthcare presents exciting opportunities for continuous, real-time,
      and noninvasive monitoring of health status. Even though electrochemical and
      optical sensing have already made great advances, there is still an urgent demand
      for alternative signal transformation in terms of miniaturization, wearability,
      conformability, and stretchability. Mechano-based transductive sensing, referred
      to the efficient transformation of biosignals into measureable mechanical
      signals, is claimed to exhibit the aforementioned desirable properties, and
      ultrasensitivity. In this Concept, a focus on pressure, strain, deflection, and
      swelling transductive principles based on micro-/nanostructures for wearable
      healthcare is presented. Special attention is paid to biophysical sensors based
      on pressure/strain, and biochemical sensors based on microfluidic pressure,
      microcantilever, and photonic crystals. There are still many challenges to be
      confronted in terms of sample collection, miniaturization, and wireless data
      readout. With continuing efforts toward solving those problems, it is anticipated
      that mechano-based transduction will provide an accessible route for multimode
      wearable healthcare systems integrated with physical, electrophysiological, and
      biochemical sensors.

PMID- 29359886
TI  - Care of older people-pharmacy's contribution: call for papers.

PMID- 29359887
TI  - Big Data.

PMID- 29359884
TI  - Benign and malignant tumors in Rubinstein-Taybi syndrome.
AB  - Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies syndrome
      associated with mutations in CREBBP (70%) and EP300 (5-10%). Previous reports
      have suggested an increased incidence of specific benign and possibly also
      malignant tumors. We identified all known individuals diagnosed with RSTS in the
      Netherlands until 2015 (n = 87) and studied the incidence and character of
      neoplastic tumors in relation to their CREBBP/EP300 alterations. The population
      based Dutch RSTS data are compared to similar data of the Dutch general
      population and to an overview of case reports and series of all RSTS individuals
      with tumors reported in the literature to date. Using the Nationwide Network and
      Registry of Histopathology and Cytopathology in the Netherlands (PALGA
      Foundation), 35 benign and malignant tumors were observed in 26/87 individuals.
      Meningiomas and pilomatricomas were the most frequent benign tumors and their
      incidence was significantly elevated in comparison to the general Dutch
      population. Five malignant tumors were observed in four persons with RSTS
      (medulloblastoma; diffuse large-cell B-cell lymphoma; breast cancer; non-small
      cell lung carcinoma; colon carcinoma). No clear genotype-phenotype correlation
      became evident. The Dutch population-based data and reported case studies
      underscore the increased incidence of meningiomas and pilomatricomas in
      individuals with RSTS. There is no supporting evidence for an increased risk for
      malignant tumors in individuals with RSTS, however, due to the small numbers this
      risk may not be fully dismissed.

PMID- 29359888
TI  - Management of paediatric high-grade blunt renal trauma: a 10-year single-centre
      UK experience.
AB  - OBJECTIVE: To report the management and outcome of paediatric patients sustaining
      high-grade blunt renal trauma. PATIENTS AND METHODS: Medical records were
      examined for all American Association for the Surgery of Trauma (AAST) grade III
      V blunt renal trauma cases admitted to a paediatric trauma centre from 2005 to
      2015. Data collected and analysed included: demographics, imaging modalities,
      management, length of hospital stay (LOS), complications, and follow-up outcomes.
      RESULTS: In all, 18 children (12 boys, six girls) with mean (range) age 11 (4-15)
      years were included. According to the AAST grading criteria, 39% (seven of 18) of
      the patients had grade III, 50% (nine of 18) grade IV, and 11% (two of 18) grade
      V injuries; 44% (eight of 18) had concomitant injuries. Most of the patients were
      managed conservatively (89%, 16 of 18), although two of the 16 subsequently
      needed JJ-stent insertion during inpatient stay for symptomatic urinoma(s). In
      all, 11% (two of 18) of the patients required interventional radiology
      service(s), involving selective embolisation for life-threatening renal tract
      haemorrhage. Blood transfusion for renal injury exclusively was required in 11%
      (two of 18) of the patients. In all, 89% (16 of 18) of the patients had at least
      one follow-up imaging study before hospital discharge; most (13 of 16) had
      ultrasonography and three required computed tomography. The median (range) LOS
      was 11 (4-31) days. In all, 17% (three of 18) of the patients required hospital
      re-admission within 30 days for complications and all required interventional
      procedures: JJ stent for urinoma (one), embolisation of renal arterio-venous
      fistula (one), and embolisation for a post-traumatic pseudoaneurysm (one).
      Overall, the median (range) follow-up was 6 (2-60) months. In all, 78% (14 of 18)
      of the patients had dimercaptosuccinic acid studies, with 11 showing reductions
      in renal function (range 3-44%). CONCLUSIONS: This study supports a care pathway
      strategy advocating conservative management of high-grade renal injuries in
      children. However, patients may experience a relative decline in renal function
      with higher grade injuries indicating the need for monitoring and follow-up.

PMID- 29359889
TI  - Periodontal and chronic kidney disease association: a systematic review and meta
      analysis.
AB  - AIM: Chronic kidney disease (CKD) and kidney failure is increasing globally and
      evidence from observational studies suggest periodontal disease may contribute to
      kidney functional decline. METHODS: Electronic searches of the PubMed, EMBASE,
      Web of Science, Scopus and Cochrane Library databases were conducted for the
      purposes of conducting a systematic review. Hand searching of reference lists was
      also performed. Meta-analysis of observational studies involving periodontal
      disease and chronic kidney disease in adults was performed. RESULTS: A total of
      17 studies were selected from an initial 4,055 abstracts. Pooled estimates
      indicated the odds of having CKD were 60% higher among patients with
      periodontitis: pooled OR 1.60 (95% CI 1.44 - 1.79, I2 35.2%, P=0.11) compared to
      those without. Conversely, a similar magnitude but non-significant higher odds of
      having periodontal disease was found among people with CKD 1.69 (95% CI: 0.84,
      3.40, I2 =89.8%, P<0.00) versus non-CKD. Meta-regression revealed study quality
      based on the Newcastle-Ottawa Scale and statistical adjustment for potential
      confounders explained almost 35% of the heterogeneity in the studies
      investigating the association between CKD and periodontitis. CONCLUSIONS:
      Moderate evidence for a positive association between periodontitis and CKD
      exists. Evidence for the opposite direction is extremely weak based on
      significant heterogeneity between studies.

PMID- 29359890
TI  - Performance comparison of two androgen receptor splice variant 7 (AR-V7)
      detection methods.
AB  - OBJECTIVES: To compare the performance of two established androgen receptor
      splice variant 7 (AR-V7) mRNA detection systems, as paradoxical responses to next
      generation androgen-deprivation therapy in AR-V7 mRNA-positive circulating tumour
      cells (CTC) of patients with castration-resistant prostate cancer (CRPC) could be
      related to false-positive classification using detection systems with different
      sensitivities. MATERIALS AND METHODS: We compared the performance of two
      established mRNA-based AR-V7 detection technologies using either SYBR Green or
      TaqMan chemistries. We assessed in vitro performance using eight genitourinary
      cancer cell lines and serial dilutions in three AR-V7-positive prostate cancer
      cell lines, as well as in 32 blood samples from patients with CRPC. RESULTS: Both
      assays performed identically in the cell lines and serial dilutions showed
      identical diagnostic thresholds. Performance comparison in 32 clinical patient
      samples showed perfect concordance between the assays. In particular, both assays
      determined AR-V7 mRNA-positive CTCs in three patients with unexpected responses
      to next-generation anti-androgen therapy. Thus, technical differences between the
      assays can be excluded as the underlying reason for the unexpected responses to
      next-generation anti-androgen therapy in a subset of AR-V7 patients. CONCLUSIONS:
      Irrespective of the method used, patients with AR-V7 mRNA-positive CRPC should
      not be systematically precluded from an otherwise safe treatment option.

PMID- 29359891
TI  - Federal Employees Health Benefits Program: Removal of Eligible and Ineligible
      Individuals From Existing Enrollments. Final rule.
AB  - The United States Office of Personnel Management (OPM) is issuing a final rule
      amending Federal Employees Health Benefits (FEHB) Program regulations to provide
      a process for removal of certain identified individuals who are found not to be
      eligible as family members from FEHB enrollments. This process would apply to
      individuals for whom there is a failure to provide adequate documentation of
      eligibility when requested. This action also amends Federal Employees Health
      Benefits (FEHB) Program regulations to allow certain eligible family members to
      be removed from existing self and family or self plus one enrollments.

PMID- 29359892
TI  - Implementation of the Provision of the Comprehensive Addiction and Recovery Act
      of 2016 Relating to the Dispensing of Narcotic Drugs for Opioid Use Disorder.
      Final rule.
AB  - The Comprehensive Addiction and Recovery Act (CARA) of 2016, which became law on
      July 22, 2016, amended the Controlled Substances Act (CSA) to expand the
      categories of practitioners who may, under certain conditions on a temporary
      basis, dispense a narcotic drug in Schedule III, IV, or V for the purpose of
      maintenance treatment or detoxification treatment. Separately, the Department of
      Health and Human Services, by final rule effective August 8, 2016, increased to
      275 the maximum number of patients that a practitioner may treat for opioid use
      disorder without being separately registered under the CSA for that purpose. The
      Drug Enforcement Administration (DEA) is hereby amending its regulations to
      incorporate these statutory and regulatory changes.

PMID- 29359893
TI  - Access to Health Insurance.

PMID- 29359894
TI  - Access to Health Insurance: State Children's Health Insurance Program.

PMID- 29359895
TI  - Business of Health: Business of Health Insurance.

PMID- 29359896
TI  - A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced
      Photodynamic Therapy.
AB  - Photodynamic therapy (PDT) has attracted ever-growing attention as a promising
      modality for cancer treatment. However, due to poor tissue penetration by light,
      photodynamic therapy has rarely been used for deeply situated tumors. This
      problem can be solved if photosensitizers are activated by microwaves (MW) that
      are able to penetrate deeply into tissues. Here, for the first time, we report
      microwave-induced photodynamic therapy and exploit copper cysteamine
      nanoparticles as a new type of photosensitizer that can be activated by
      microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in
      vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant
      cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The
      heating effects and the release of copper ions from Cu-Cy upon MW stimulation are
      the main mechanisms for the generation of reactive oxygen species that are lethal
      bullets for cancer destruction. The copper cysteamine nanoparticle-based
      microwave-induced photodynamic therapy opens a new door for treating cancer and
      other diseases.

PMID- 29359897
TI  - Business of Health: Business of Healthcare.

PMID- 29359899
TI  - Business of Health: International Healthcare.

PMID- 29359898
TI  - The Morphology of Self-Assembled Lipid-Based Nanoparticles Affects Their Uptake
      by Cancer Cells.
AB  - The morphology of nanoparticles (NPs) has been presumed to play an important role
      in cellular uptake and in vivo stability. This report experimentally demonstrates
      such dependence by using two types of uniform-sized self-assembled lipid-based
      NPs, namely nanodiscs and nanovesicles, composed of identical lipid composition.
      The morphology is characterized by small angle neutron scattering, dynamic light
      scattering and transmission electron microscopy. Both NPs have similar bio
      stability in serum and cellular cytotoxicity. However, cellular uptake of the
      nanodiscs at 37  degrees C is consistently and significantly higher than that of
      the vesicles according to the uptake results of several human cancer cell lines,
      i.e., CCRFCEM, KB, and OVCAR-8, indicating a strong morphological dependence of
      cellular internalization. Further studies on such morphological dependence using
      CCRF-CEM reveals that vesicles only use Clathrin- and caveolae-mediated endocytic
      pathways, while nanodiscs also take the additional routes of macropinocytosis and
      microtubule-mediated endocytosis.

PMID- 29359900
TI  - Emergency care.

PMID- 29359901
TI  - Designing of Combined Nano and Microfiber Network by Immobilization of Oxidized
      Cellulose Nanofiber on Polycaprolactone Fibrous Scaffold.
AB  - In this study, the immobilization of oxidized cellulose nanofiber (OCNF) network
      on the polycaprolactone (PCL) fibrous scaffold was performed by the aminolysis
      procedure through electrospinning and layer by layer (LBL) techniques. The
      morphology of the fibrous scaffold was examined by field emission scanning
      electron microscopy (FE-SEM), and it indicated that after immobilization of OCNF
      on PCL, the unique nanofiber and nano network was created. Moreover, the physical
      and chemical properties of samples were examined using X-ray photoelectron
      spectroscopy (XPS), Fourier transform spectroscopy (FT-IR), thermogravimetric
      analysis (TGA), water contact angle measurement, and BSA adsorption properties.
      Furthermore, the cellular responses to PCL scaffold with and without modification
      by OCNF were examined by seeding rat bone marrow stem cells (RBMSCs) on the
      fibrous scaffold for assessing cell attachment, cell viability, and
      proliferation. Thus, the present study focused on preparation and
      characterization of a membrane and tubular scaffold with a unique nanostructure,
      which is an excellent candidate for use as a blood vessel scaffold graft.

PMID- 29359902
TI  - Healthcare facilities.

PMID- 29359903
TI  - Nanohybrid Electro-Coatings Toward Therapeutic Implants with Controlled Drug
      Delivery Potential for Bone Regeneration.
AB  - Coatings of metallic implants facilitate a new bioactive interface that favors
      osteogenic responses and bone formation. Providing a therapeutic capacity to the
      coatings, involving with a sustainable and controllable delivery of drug
      molecules, significantly improves the bone regenerative potential. Here we design
      a novel nanocomposite coating, made of mesoporous silica-shelled hydroxyapatite
      (MS-HA) nanoparticles and chitosan (Chi), incorporating osteogenic drug
      dexamethasone phosphate (Dex(P)) within the MS-HA, by the process of an
      electrophoretic deposition (EPD). MS-HA, produced by a sol-gel reaction of silica
      onto an HA nanorod, exhibited mono-dispersed core-shell nanoparticles with a size
      of ~40 nm and a shell thickness of ~25 nm. The highly mesoporous structure
      enabled an effective loading of Dex(P) onto the nanocarriers, showing a loading
      capacity as high as 15% by weight. The Dex(P) loaded MS-HA were homogenized with
      Chi in acidic ethanol/water to allow for the EPD process. Nanocomposite coatings
      were produced well, forming thicknesses a few micrometers largely tunable with
      EPD parameters and exhibiting MS-HA nanoparticles evenly distributed within Chi
      matrix. While Dex(P) release from the bare MS-HA nanocarrier was very abrupt,
      showing a complete release within 24 h, the Dex(P) release from the nanocomposite
      coatings profiled a highly sustainable pattern over a month. Rat mesenchymal stem
      cells cultured on the Dex(P)-releasing coatings were substantially stimulated to
      an osteoblastic lineage, presenting enhanced alkaline phosphate activity and
      higher levels of osteogenic genes, with respect to coatings free of Dex(P). An
      indirect culture test also confirmed the long-term release effects of Dex(P) from
      the coatings over 4 weeks. The currently-developed nanocomposite EPD coatings,
      with a capacity to load osteogenic drug at large quantity and to deliver for a
      long-term period, are considered as a promising therapeutic coating platform for
      metallic bone implants.

PMID- 29359904
TI  - Healthcare Workforce.

PMID- 29359905
TI  - Healthcare Information Technology.

PMID- 29359906
TI  - Long-Term Antibacterial Performance and Bioactivity of Plasma-Engineered Ag
      NPs/TiO2
AB  - We prepared TiO2 nanotubes (NT) on commercially pure titanium (cp-Ti) substrate
      by plasma electrolyte oxidation and adapted magnetron sputtering for
      incorporation of Ag-nanoparticles (Ag-NPs) onto the nanotubes (Ag-NPs/TiO2
      nanotube). Power input to the Ag target per unit time was varied (5, 10, 15
      W/cm2) to fabricate different shapes of Agnanoparticles onto the nanotubes while
      net energy input was fixed by maintaining a constant total sputter time (30, 15,
      10 s, respectively). For investigation of experimental samples' characteristics,
      FE-SEM, TEM, EDS, XRD, XPS, SPM analysis and contact angles measurement was
      carried out. Through these characterization, plasma engineered Ag-NPs was
      successfully formed on/in the entire nanotube structure. In terms of
      antibacterial ability, plasma engineered Ag-NPs/TiO2 nanotubes samples
      significantly reduced S. aureus colony numbers compared with control. Also,
      simulated body fluid immersion tests with hydroxyapatite showed ion precipitation
      onto the surface of all experimental groups, confirmed by XRD and EDS analysis.
      However, plasma engineered Ag-NPs/TiO2 nanotubes groups were not cytotoxic.
      Furthermore, MC3T3-E1 cells were cultured on Ag-NPs/TiO2 nanotubes groups to
      evaluate the effect of nanostructured surface on cell functionality such as a
      cell proliferation and ALP activity. Ag-NPs/TiO2 nanotubes have both
      biocompatible and antibacterial characteristics.

PMID- 29359907
TI  - Medical Errors and Patient Safety: Reducing Medical Errors and Improving Patient
      Safety.

PMID- 29359909
TI  - Exploration of C-H Transformations of Aldehyde Hydrazones: Radical Strategies and
      Beyond.
AB  - The chemistry of hydrazones has gained great momentum due to their involvement
      throughout the evolution of organic synthesis. Herein, we discuss the tremendous
      developments in both the methodology and application of hydrazones. Hydrazones
      can be recognized not only as synthetic equivalents to aldehydes and ketones but
      also as versatile synthetic building blocks. Consequently, they can participate
      in a range of practical synthetic transformations. Furthermore, hydrazone
      derivatives display a broad array of biological activities and have been widely
      applied as pharmaceuticals. Owing to the weak directing group effect of simple
      aldehydes and ketones in C-H bond functionalizations, the C-H bond
      functionalizations of hydrazones that have been developed in the past five years
      represent a significant step forward. These novel transformations open a new door
      to a broader library of functionalized and complex small molecules. Moreover, a
      wide range of biologically important N-heterocycles (dihydropyrazoles, pyrazoles,
      indazoles, cinnolines, etc.) can be efficiently synthesized in an atom- and step
      economical manner through single, double, or triple C-H bond functionalizations
      of hydrazones. Both radical C-H functionalizations and transition-metal-catalyzed
      directing-group strategies have enhanced the synthetic utility of hydrazones in
      the chemical community because these strategies solve the long-standing challenge
      of C-H functionalizations adjacent to aldehydes and ketones. We began this study
      based on our ongoing interest in visible-light photoredox catalysis. Visible
      light photoredox catalysis has become a powerful tool in contemporary synthetic
      chemistry due to its remarkable advantages in sustainability and use of radical
      chemistry. By exploiting a photoredox-catalyzed aminyl radical polar crossover
      (ARPC) strategy, we successfully achieved visible-light-induced C(sp2)-H
      difluoroalkylation, trifluoromethylation, and perfluoroalkylation of aldehyde
      derived hydrazones. This intriguing result was later applied in the C(sp2)-H
      amination of hydrazones and a cascade cyclization reaction for the synthesis of
      polycyclic compounds. Encouraged by this redox-neutral C-H functionalization of
      aldehyde hydrazones, we extended the oxidative C-H/P-H cross-coupling method,
      which represents a novel and efficient method for the synthesis of alpha
      iminophosphine oxides. Furthermore, an elegant [3 + 2] cycloaddition of azides
      and aldehyde hydrazones for the synthesis of functionalized tetrazoles was
      advantageously developed during our investigation of the oxidative C(sp2)-H
      azidation of aldehyde hydrazones with TMSN3. The sequential C(sp2)-H/C(sp3)-H
      bond functionalization of aldehyde-derived hydrazones with simple 2,2-dibromo-1,3
      dicarbonyls was achieved by employing relay photoredox catalysis, and it provides
      a novel method of accessing bioactive fused dihydropyrazole derivatives. The
      notable feature of this approach was further reflected in the formal [4 + 1]
      annulation of aldehyde-derived N-tetrahydroisoquinoline hydrazones with 2-bromo
      1,3-dicarbonyls. To complement these radical C-H functionalization strategies, we
      recently applied a directing-group strategy in the Rh-catalyzed C(aldehyde)-H
      functionalization of aldehyde-derived hydrazones for the synthesis of distinctive
      and bioactive 1H-indazole scaffolds. In summary, this Account presents recent
      contributions to the exploration, development, mechanistic insights, and
      synthetic applications of C-H bond functionalizations of aldehyde hydrazones.

PMID- 29359908
TI  - Potent Inhibitors of Mycobacterium tuberculosis Growth Identified by Using in
      Cell NMR-based Screening.
AB  - In-cell NMR spectroscopy was used to screen for drugs that disrupt the
      interaction between prokaryotic ubiquitin like protein, Pup, and mycobacterial
      proteasome ATPase, Mpa. This interaction is critical for Mycobacterium
      tuberculosis resistance against nitric oxide (NO) stress; interruption of this
      process was proposed as a mechanism to control latent infection. Three compounds
      isolated from the NCI Diversity set III library rescued the physiological
      proteasome substrate from degradation suggesting that the proteasome degradation
      pathway was selectively targeted. Two of the compounds bind to Mpa with sub
      micromolar to nanomolar affinity, and all three exhibit potency toward
      mycobacteria comparable to antibiotics currently available on the market,
      inhibiting growth in the low micromolar range.

PMID- 29359910
TI  - Nitrogen-Doped Single-Walled Carbon Nanohorns as a Cost-Effective Carbon Host
      toward High-Performance Lithium-Sulfur Batteries.
AB  - Nitrogen-doped single-walled carbon nanohorns (N-SWCNHs) are porous carbon
      material characterized by unique horn-shape structures with high surface areas
      and good conductivity. Moreover, they can be mass-produced (tons/year) using a
      novel proprietary process technology making them an attractive material for
      various industrial applications. One of the applications is the encapsulation of
      sulfur, which turns them as promising conductive host materials for lithium
      sulfur batteries. Therefore, we explore for the first time the electrochemical
      performance of industrially produced N-SWCNHs as a sulfur-encapsulating
      conductive material. Fabrication of lithium-sulfur cells based on N-SWCNHs with
      sulfur composite could achieve a remarkable initial gravimetric capacity of 1650
      mA h g-1, namely equal to 98.5% of the theoretical capacity (1675 mA h g-1), with
      an exceptional sulfur content as high as 80% in weight. Using cyclic
      chronopotentiometry and impedance spectroscopy, we also explored the dissolution
      mechanism of polysulfides inside the electrolyte.

PMID- 29359911
TI  - Robust Coatings via Catechol-Amine Codeposition: Mechanism, Kinetics, and
      Application.
AB  - Bioinspired polyphenol/polyamine codeposition has been demonstrated by the
      competence for surface modification; however, the reaction processes including
      mechanism and kinetics remain superficially understood. In this work, the
      catechol (CA)-amine reaction has been thoroughly investigated by using CA and two
      amines m-phenylenediamine and piperazine. We verify that both primary and
      secondary amines are prone to link with CA through Michael addition to form
      polyphenol/polyamine oligomers under aerobic and mild-alkaline conditions.
      Molecular simulations indicate that the Michael addition products are dominant
      for both aromatic and aliphatic amines with CA, which supports the durable chem-
      and phystability of the codeposited coatings. The aggregation kinetics of
      polyphenol/polyamine is provided for the first time, and the formed aggregates
      show high-adhesive properties, which can be deposited as the skin layers for high
      performance nanofiltration membranes.

PMID- 29359912
TI  - Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes
      Promotes Bone Regeneration.
AB  - Exosomes, nanoscale extracellular vesicles functioning as cell-to-cell
      communicators, are an emerging promising therapeutic in the field of bone tissue
      engineering. Here, we report the construction and evaluation of a novel cell-free
      tissue-engineered bone that successfully accelerated the restoration of critical
      sized mouse calvarial defects through combining exosomes derived from human
      adipose-derived stem cells (hASCs) with poly(lactic-co-glycolic acid) (PLGA)
      scaffolds. The exosomes were immobilized on the polydopamine-coating PLGA
      (PLGA/pDA) scaffolds under mild chemical conditions. Specifically, we
      investigated the effects of hASC-derived exosomes on the osteogenic,
      proliferation, and migration capabilities of human bone marrow-derived
      mesenchymal stem cells in vitro and optimized their osteoinductive effects
      through osteogenic induction. Furthermore, an in vitro assay showed exosomes
      could release from PLGA/pDA scaffold slowly and consistently and in vivo results
      showed this cell-free system enhanced bone regeneration significantly, at least
      partially through its osteoinductive effects and capacities of promoting
      mesenchymal stem cells migration and homing in the newly formed bone tissue.
      Therefore, overall results demonstrated that our novel cell-free system comprised
      of hASC-derived exosomes and PLGA/pDA scaffold provides a new therapeutic
      paradigm for bone tissue engineering and showed promising potential in repairing
      bone defects.

PMID- 29359913
TI  - Ultrathin Shape Change Smart Materials.
AB  - With the discovery of graphene, significant research has focused on the
      synthesis, characterization, and applications of ultrathin materials. Graphene
      has also brought into focus other ultrathin materials composed of organics,
      polymers, inorganics, and their hybrids. Together, these ultrathin materials have
      unique properties of broad significance. For example, ultrathin materials have a
      large surface area and high flexibility which can enhance conformal contact in
      wearables and sensors leading to improved sensitivity. When porous, the short
      transverse diffusion length in these materials allows rapid mass transport.
      Alternatively, when impermeable, these materials behave as an ultrathin barrier.
      Such controlled permeability is critical in the design of encapsulation and drug
      delivery systems. Finally, ultrathin materials often feature defect-free and
      single-crystal-like two-dimensional atomic structures resulting in superior
      mechanical, optical, and electrical properties. A unique property of ultrathin
      materials is their low bending rigidity, which suggests that they could easily be
      bent, curved, or folded into 3D shapes. In this Account, we review the emerging
      field of 2D to 3D shape transformations of ultrathin materials. We broadly define
      ultrathin to include materials with a thickness below 100 nm and composed of a
      range of organic, inorganic, and hybrid compositions. This topic is important for
      both fundamental and applied reasons. Fundamentally, bending and curving of
      ultrathin films can cause atomistic and molecular strain which can alter their
      physical and chemical properties and lead to new 3D forms of matter which behave
      very differently from their planar precursors. Shape change can also lead to new
      3D architectures with significantly smaller form factors. For example, 3D
      ultrathin materials would occupy a smaller space in on-chip devices or could
      permeate through tortuous media which is important for miniaturized robots and
      smart dust applications. Our Account highlights several differences between
      ultrathin and traditional shape change materials. The latter is typically
      associated with hydrogels, liquid crystals, or shape memory elastomers. As
      compared to bulk materials, ultrathin materials can much more easily bend and
      fold due to the significantly reduced bending modulus. Consequently, it takes
      much less energy to alter the shape of ultrathin materials, and even small
      environmental stimuli can trigger a large response. Further, the energy barriers
      between different configurations are small which allow a variety of conformations
      and enhances programmability. Finally, due to their ultrathin nature, the shape
      changes are typically not slowed down by sluggish mass or thermal transport, and
      thus, responses can be much faster than those of bulk materials. The latter point
      is important in the design of high-speed actuators. Consequently, ultrathin
      materials could enable low-power, rapid, programmable, and complex shape
      transformations in response to a broad range of stimuli such as pH, temperature,
      electromagnetic fields, or chemical environments. The Account also includes a
      discussion of applications, important challenges, and future directions.

PMID- 29359914
TI  - Kirigami-Inspired Structures for Smart Adhesion.
AB  - Spatially controlled layouts of elasticity can provide enhanced adhesion over
      homogeneous systems. Emerging techniques in kirigami, where designed cuts in
      materials impart highly tunable stiffness and geometry, offer an intriguing
      approach to create well-defined layouts of prescribed elastic regions. Here, we
      show that kirigami-inspired structures at interfaces provide a new mechanism to
      spatially control and enhance adhesion strength while providing directional
      characteristics for smart interfaces. We use kirigami-inspired cuts to define
      stiff and compliant regions, where above a critical, material-defined length
      scale, bending rigidity and contact width can be tuned to enhance adhesive force
      capacity by a factor of ~100 across a spatially patterned adhesive sheet. The
      directional nature of these designs also imparts anisotropic responses, where
      peeling in different directions results in anisotropic adhesion ratios of ~10.
      Experimental results are well-supported by theoretical predictions in which the
      bending rigidity and contact width of kirigami-inspired structures and
      interconnects control the adhesive capacity. These new interfacial structures and
      design criteria provide diverse routes for advanced adhesive functionality,
      including spatially controlled systems, wearable kirigami-inspired electronics,
      and anisotropic kirigami-inspired bandages that enable strong adhesive capacity
      while maintaining easy release.

PMID- 29359915
TI  - Preparation of Dual-Emitting Ln@UiO-66-Hybrid Films via Electrophoretic
      Deposition for Ratiometric Temperature Sensing.
AB  - Engineering novel dual-emitting metal-organic frameworks (MOFs) with wide
      emission ranges for application as ratiometric temperature sensors is still a
      challenge. In this paper, two novel dual-emitting MOFs with intergrated
      lanthanide metals and luminescent ligand in a UiO-66-type structure, named Ln@UiO
      66-Hybrid, were prepared via the combination of postsynthetic modification and
      postsynthetic exchange methods. Subsequently, the as-synthesized MOFs were
      deposited onto fluorine tin oxide substrates through electrophoretic deposition
      by taking advantage of the charges from the unmodified carboxylic groups of the
      MOFs. The as-prepared Tb@UiO-66-Hybrid and Eu@UiO-66-Hybrid films were applied to
      detect temperature changes. The resulting Tb@UiO-66-Hybrid film exhibited good
      temperature-sensing properties with a relative sensitivity of up to 2.76% K-1 in
      the temperature range of 303-353 K. In addition, the Eu@UiO-66-Hybrid film showed
      excellent temperature-sensing performance based on the energy transfer between
      the luminescent ligand (H2NDC) and europium ions with a relative sensitivity of
      up to 4.26% K-1 in the temperature range of 303-403 K.

PMID- 29359917
TI  - Development of [ Carbonyl-11C]AZ13198083, a Novel Histamine Type-3 Receptor
      Radioligand with Favorable Kinetics.
AB  - The histamine subtype-3 receptor (H3R) is implicated in a range of central
      nervous system disorders, and several radioligands have been developed for H3R
      positron emission tomography imaging. However, a limitation of currently used PET
      radioligands for H3R is the slow binding kinetics in high density brain regions.
      To address this, we herein report the development of three novel candidate H3R
      radioligands, namely, [ carbonyl-11C]AZ13153556 ([ carbonyl-11C]4), [ carbonyl
      11C]AZD5213([ carbonyl-11C]5), and [ carbonyl-11C]AZ13198083 ([ carbonyl-11C]6),
      and their subsequent preclinical evaluation in nonhuman primates (NHP).
      Radioligands [ carbonyl-11C]4-6 were produced and isolated in high radioactivity
      (>1000 MBq), radiochemical purity (>99%), and moderate molar activity (19-28
      GBq/MUmol at time of injection) using a palladium-mediated 11C-aminocarbonylation
      protocol. All three radioligands showed high brain permeability as well as a
      regional brain radioactivity distribution in accordance with H3R expression
      (striatum > cortex > cerebellum). [ Carbonyl-11C]6 displayed the most favorable
      in vivo kinetics and brain uptake, with an early peak in the striatal time
      activity curve followed by a progressive washout from the brain. The specificity
      and on-target kinetics of [ carbonyl-11C]6 were next investigated in pretreatment
      and displacement studies. After pretreatment or displacement with 5 (0.1 mg/kg),
      a uniformly low distribution of radioactivity across the NHP brain was observed.
      Collectively, this work demonstrates that [ carbonyl-11C]6 is a promising
      candidate for H3R imaging in human subjects.

PMID- 29359916
TI  - Functional Modulation of Voltage-Gated Sodium Channels by a FGF14-Based
      Peptidomimetic.
AB  - Protein-protein interactions (PPI) offer unexploited opportunities for CNS drug
      discovery and neurochemical probe development. Here, we present ZL181, a novel
      peptidomimetic targeting the PPI interface of the voltage-gated Na+ channel
      Nav1.6 and its regulatory protein fibroblast growth factor 14 (FGF14). ZL181
      binds to FGF14 and inhibits its interaction with the Nav1.6 channel C-tail. In
      HEK-Nav1.6 expressing cells, ZL181 acts synergistically with FGF14 to suppress
      Nav1.6 current density and to slow kinetics of fast inactivation, but antagonizes
      FGF14 modulation of steady-state inactivation that is regulated by the N-terminal
      tail of the protein. In medium spiny neurons in the nucleus accumbens, ZL181
      suppresses excitability by a mechanism that is dependent upon expression of FGF14
      and is consistent with a state-dependent inhibition of FGF14. Overall, ZL181 and
      derivatives could lay the ground for developing allosteric modulators of Nav
      channels that are of interest for a broad range of CNS disorders.

PMID- 29359918
TI  - A Peptidomimetic Antibiotic Interacts with the Periplasmic Domain of LptD from
      Pseudomonas aeruginosa.
AB  - The outer membrane (OM) in Gram-negative bacteria is an asymmetric bilayer with
      mostly lipopolysaccharide (LPS) molecules in the outer leaflet. During OM
      biogenesis, new LPS molecules are transported from their site of assembly on the
      inner membrane to the OM by seven LPS transport proteins (LptA-G). The complex
      formed between the integral beta-barrel OM protein LptD and the lipoprotein LptE
      is responsible for transporting LPS from the periplasmic side of the OM to its
      final location on the cell surface. Because of its essential function in many
      Gram-negative bacteria, the LPS transport pathway is an interesting target for
      the development of new antibiotics. A family of macrocyclic peptidomimetics was
      discovered recently that target LptD and inhibit LPS transport specifically in
      Pseudomonas spp. The related molecule Murepavadin is in clinical development for
      the treatment of life-threatening infections caused by P. aeruginosa. To
      characterize the interaction of these antibiotics with LptD from P. aeruginosa,
      we characterized the binding site by cross-linking to a photolabeling probe. We
      used a hypothesis-free mass spectrometry-based proteomic approach to provide
      evidence that the antibiotic cross-links to the periplasmic segment of LptD,
      containing a beta-jellyroll domain and an N-terminal insert domain characteristic
      of Pseudomonas spp. Binding of the antibiotic to the periplasmic segment is
      expected to block LPS transport, consistent with the proposed mode of action and
      observed specificity of these antibiotics. These insights may prove valuable for
      the discovery of new antibiotics targeting the LPS transport pathway in other
      Gram-negative bacteria.

PMID- 29359919
TI  - Biocompatible Poly(catecholamine)-Film Electrode for Potentiometric Cell Sensing.
AB  - Surface-coated poly(catecholamine) (pCA) films have attracted attention as
      biomaterial interfaces owing to their biocompatible and physicochemical
      characteristics. In this paper, we report that pCA-film-coated electrodes are
      useful for potentiometric biosensing devices. Four different types of pCA film, l
      dopa, dopamine, norepinephrine, and epinephrine, with thicknesses in the range of
      7-27 nm were electropolymerized by oxidation on Au electrodes by using cyclic
      voltammetry. By using the pCA-film electrodes, the pH responsivities were found
      to be 39.3-47.7 mV/pH within the pH range of 1.68 to 10.01 on the basis of the
      equilibrium reaction with hydrogen ions and the functional groups of the pCAs.
      The pCA films suppressed nonspecific signals generated by other ions (Na+, K+,
      Ca2+) and proteins such as albumin. Thus, the pCA-film electrodes can be used in
      pH-sensitive and pH-selective biosensors. HeLa cells were cultivated on the
      surface of the pCA-film electrodes to monitor cellular activities. The surface
      potential of the pCA-film electrodes changed markedly because of cellular
      activity; therefore, the change in the hydrogen ion concentration around the
      cell/pCA-film interface could be monitored in real time. This was caused by
      carbon dioxide or lactic acid that is generated by cellular respiration and
      dissolves in the culture medium, resulting in the change of hydrogen
      concentration. pCA-film electrodes are suitable for use in biocompatible and pH
      responsive biosensors, enabling the more selective detection of biological
      phenomena.

PMID- 29359920
TI  - Rapid Screening of DNA-Ligand Complexes via 2D-IR Spectroscopy and ANOVA-PCA.
AB  - Two-dimensional infrared spectroscopy (2D-IR) is well established as a
      specialized, high-end technique for measuring structural and solvation dynamics
      of biological molecules. Recent technological developments now make it possible
      to acquire time-resolved 2D-IR spectra within seconds, and this opens up the
      possibility of screening-type applications comparing spectra spanning multiple
      samples. However, such applications bring new challenges associated with finding
      accurate, efficient methodologies to analyze large data sets in a timely,
      informative manner. Here, we demonstrate such an application by screening 2016 2D
      IR spectra of 12 double-stranded DNA oligonucleotides obtained in the presence
      and absence of binding therapeutic molecule Hoechst 33258. By applying analysis
      of variance combined with principal component analysis (ANOVA-PCA) to 2D-IR data
      for the first time, we demonstrate the ability to efficiently retrieve the base
      composition of a DNA sequence and discriminate ligand-DNA complexes from unbound
      sequences. We further show accurate differentiation of the induced-fit and rigid
      body binding modes that is key to identifying optimal binding interactions of
      Hoechst 33258, while ANOVA-PCA results across the full sequence range correlate
      directly with thermodynamic indicators of ligand-binding strength that require
      significantly longer data acquisition times to obtain.

PMID- 29359921
TI  - Synchrotron-Based Fourier Transform Infrared Microspectroscopy (MUFTIR) Study on
      the Effect of Alzheimer's Abeta Amorphous and Fibrillar Aggregates on PC12 Cells.
AB  - Amyloid plaques made of aggregated Abeta amyloid peptide are a pathological
      hallmark in brains affected by Alzheimer's disease (AD). Moreover, the amyloid
      peptide may play a major role in the onset and development of the disease in
      association to other factors such as oxidative stress. Although the molecular
      nature of the amyloid toxic species is still unknown, there is experimental
      evidence pointing to their nonfibrillar nature. In the present paper, we report
      the use of synchrotron Fourier transform infrared microspectroscopy (MUFTIR) for
      the study of the effect of two different types of Alzheimer's Abeta(1-40)
      aggregates (amyloid fibrils and granular nonfibrillar aggregates) on PC12
      cultured cells. The principal component analysis (PCA) of the infrared spectra
      has been complemented with a correlation analysis, which permits one to study
      different spectroscopic parameters as a function of peptide aggregation. The
      results show that the treatment of PC12 cells with amorphous aggregates generates
      a higher degree of oxidation in the vicinity of the amyloid aggregates than the
      treatment with preformed amyloid fibrils. These results, which permit, for the
      first time, the in situ colocalization of amyloid aggregates and oxidized
      macromolecules in cell culture, are in agreement with previous data from our
      group, showing that oxidation was higher in regions surrounding amyloid plaques
      in human brain samples affected by AD.

PMID- 29359922
TI  - Linear and Differential Ion Mobility Separations of Middle-Down Proteoforms.
AB  - Comprehensive characterization of proteomes comprising the same proteins with
      distinct post-translational modifications (PTMs) is a staggering challenge. Many
      such proteoforms are isomers (localization variants) that require separation
      followed by top-down or middle-down mass spectrometric analyses, but condensed
      phase separations are ineffective in those size ranges. The variants for "middle
      down" peptides were resolved by differential ion mobility spectrometry (FAIMS),
      relying on the mobility increment at high electric fields, but not previously by
      linear IMS on the basis of absolute mobility. We now use complete histone tails
      with diverse PTMs on alternative sites to demonstrate that high-resolution linear
      IMS, here trapped IMS (TIMS), broadly resolves the variants of ~50 residues in
      full or into binary mixtures quantifiable by tandem MS, largely thanks to
      orthogonal separations across charge states. Separations using traveling-wave
      (TWIMS) and/or involving various time scales and electrospray ionization source
      conditions are similar (with lower resolution for TWIMS), showing the
      transferability of results across linear IMS instruments. The linear IMS and
      FAIMS dimensions are substantially orthogonal, suggesting FAIMS/IMS/MS as a
      powerful platform for proteoform analyses.

PMID- 29359923
TI  - Unsupervised Analysis of Big ToF-SIMS Data Sets: a Statistical Pattern
      Recognition Approach.
AB  - We present a new method, fast and low demanding in terms of CPU performances,
      which is able to extract latent chemical information from ToF-SIMS big data sets,
      such as those arising from chemical imaging, by working on the unbinned raw data
      files. The method is able to evaluate the similarity/dissimilarity of very low
      intensity spectra, such as those arising from a single pixel, in terms of
      symmetry and asymmetry relationships of the count distribution in the Fourier
      transform domain. The tests performed so far on model samples show that the
      method supplies results that, without sacrificing mass or spatial resolution, are
      equivalent, at least, to those achievable by an experienced ToF-SIMS user by
      applying PCA techniques.

PMID- 29359924
TI  - Diffusion of Water through the Dual-Porosity Swelling Clay Mineral Vermiculite.
AB  - Prediction of water and solute migration in natural clay-based materials requires
      a detailed understanding of the roles played by different porosity types (around
      or inside clay particles) on the overall transfer process. For smectite, a
      reference material for the design of migration models, this discrimination is
      complex because of osmotic swelling of the structure under water-saturated
      conditions. Diffusion experiments with a water tracer (HDO) were conducted on 0.1
      0.2, 1-2, and 10-20 MUm size fractions of Na-vermiculite, a swelling clay mineral
      with no osmotic swelling. Results obtained for the two finest fractions suggest
      that osmotic swelling and the associated impact on pore structure are responsible
      for the low De values reported in the literature for smectite compared to those
      of vermiculite. When considering only interparticle porosity, De values for
      vermiculite are similar to those reported for nonporous grains (Na-kaolinite and
      Na-illite). This indicates that interparticle porosity has a primary effect on
      the overall water diffusion process, whereas interlayer porosity is shown to
      imply a small proportion of HDO adsorption. This study provides evidence that
      vermiculite is a promising reference mineral for the understanding of the roles
      played by pore structure and mineral-water interaction in the transport
      properties of water in claystones and for associated refinement of dual-porosity
      diffusion models.

PMID- 29359925
TI  - Biodegradation of Ethyl Carbamate and Urea with Lysinibacillus sphaericus MT33 in
      Chinese Liquor Fermentation.
AB  - It is important to reduce the concentration of ethyl carbamate (EC) in fermented
      foods. However, controlling the formation of EC and its precursor urea is
      difficult in spontaneous food fermentation because urea is a natural product of
      nitrogen metabolism. Biodegradation is a better solution to reduce the
      concentration of EC. This study aimed to reduce the concentration of EC in
      Chinese liquor via an indigenous strain Lysinibacillus sphaericus MT33. This
      strain produced urethanase (940 U/L) and urease (1580 U/L) and degraded 76.52% of
      EC and 56.48% of urea. After inoculation in liquor fermentation, the maximal
      relative abundance of Lysinibacillus increased from 0.02% to 8.46%, the final EC
      and urea contents decreased by 41.77% and 28.15%. Moreover, the concentration of
      EC decreased by 63.32% in liquor. The negative correlation between abundance of
      Lysinibacillus and contents of EC and urea indicated the effect of L. sphaericus
      on EC and urea degradation.

PMID- 29359926
TI  - Reaction Chemistry of Silver(I) Trifluoromethanesulfonate Complexes of Nitrogen
      Confused C-Scorpionates.
AB  - Two new C-scorpionate ligands with a bis(3,5-dimethylpyrazol-1-yl)methyl group
      bound to the 3 position of either an N-tosyl (TsL*) or an N-H pyrazole (HL*) ring
      have been prepared. The silver(I) complexes of these new ligands and the two
      previously reported analogous ligands with unsubstituted bis(pyrazol-1-yl)methyl
      groups (TsL and HL) in both 1:1 and 2:1 ligand/metal ratios were investigated to
      explore the effects of ligand sterics on their physical and chemical properties.
      The structurally characterized derivatives of the type [Ag(L)2](OTf) are four
      coordinate, where the confused pyrazolyl is not bound to the metal. On the other
      hand, three 1:1 complexes [Ag(L)](OTf) had all pyrazolyls bound, while the MU
      kappa1,kappa1-TsL derivative had an unbound confused pyrazolyl. The molecularity
      of the latter four ranged from polymeric to dimeric to monomeric in the solid
      with increasing steric bulk of the ligand. The utility of these complexes in
      stoichiometric ligand-transfer reactions and in styrene aziridination was
      demonstrated. Thus, tricarbonylmanganese(I) complexes were prepared as
      kinetically inert models for comparative solution diffusion NMR studies. Also,
      [Fe(HL)2](OTf)2 was prepared for similar reasons and to compare the effects of
      anion on spin-crossover properties.

PMID- 29359927
TI  - Phosphatase-Mediated Hydrolysis of Linear Polyphosphates.
AB  - Polyphosphates are a group of phosphorus (P) containing molecules that are
      produced by a wide range of microorganisms and human activities. Although
      polyphosphates are ubiquitous in aquatic environments and are of environmental
      significance, little is known about their transformation and cycling. This study
      characterized the polyphopshate-hydrolysis mechanisms of several representative
      phosphatase enzymes and evaluated the effects of polyphosphate chain length,
      light condition, and calcium (Ca2+). 31P nuclear magnetic resonance (NMR)
      spectroscopy was used to monitor the dynamic changes of P molecular configuration
      during polyphosphate hydrolysis and suggested a terminal-only degradation pathway
      by the enzymes. Such mechanism enabled the quantification of the hydrolysis rates
      by measuring orthophosphate production over time. At the same initial
      concentration of polyphosphate molecules, the hydrolysis rates were independent
      of chain length. The hydrolysis of polyphosphate was also unaffected by light
      condition, but was reduced by the presence of Ca2+. The released orthophosphates
      formed Ca-phosphate precipitates in the presence of Ca2+, likely in amorphous
      phases. Results from this study lay the foundation for better understanding the
      chemical processes governing polyphosphate transport and transformation in
      various environmental settings.

PMID- 29359928
TI  - De Novo Sequencing of Tryptic Phosphopeptides Using Matrix-Assisted Laser
      Desorption/Ionization Based Tandem Mass Spectrometry with Hydrogen Atom
      Attachment.
AB  - Phosphorylation is the most abundant protein modification, and tandem mass
      spectrometry (MS/MS) with radical-based fragmentation techniques has proven to be
      a promising method for phosphoproteomic applications, owing to its ability to
      determine phosphorylation sites on proteins. The radical-induced fragmentation
      technique involves the attachment or abstraction of hydrogen to peptides in an
      ion trap mass spectrometer, in a process called hydrogen attachment/abstraction
      dissociation (HAD), which has only been recently developed. In the present
      investigation, we have analyzed model phosphopeptides and phosphoprotein digests
      using HAD-MS/MS, combined with matrix-assisted laser desorption/ionization
      (MALDI), in order to demonstrate the usefulness of the HAD-MS/MS-based analytical
      method. The tryptic peptides were categorized as arginine- and lysine-terminated
      peptides, and MALDI HAD-MS/MS is found to facilitate the sequencing of arginine
      terminated tryptic peptides, because of the selective observation of C-terminal
      side fragment ions. In contrast, MALDI HAD-MS/MS of lysine-terminated tryptic
      peptides produced both N- and C-terminal side fragments, such that the mass
      spectra were complex. The guanidination of peptide converted lysine into
      homoarginine, which facilitated the interpretation of MALDI HAD-MS/MS mass
      spectra. The present method was useful for de novo sequencing of tryptic
      phosphopeptides.

PMID- 29359929
TI  - Spectroscopic Indicators for Cytotoxicity of Chlorinated and Ozonated Effluents
      from Wastewater Stabilization Ponds and Activated Sludge.
AB  - We investigated chronic mammalian cell cytotoxicity of wastewaters from four
      sources and their optical spectroscopic properties with or without chlorination
      or ozonation. Samples from effluents of activated sludge, nitrification tower,
      facultative waste stabilization pond, and maturation waste stabilization pond
      were either chlorinated or ozonated. The wastewater samples were analyzed for
      fluorescence excitation emission matrix, specific fluorescence index (SFI), and
      specific UV absorbance at 254 nm (SUVA). Before and after disinfection the
      wastewater samples were quantitatively analyzed for in vitro mammalian cell
      cytotoxicity. We found that the organic extracts from the ozonated samples
      induced lower cytotoxicity responses than those from the chlorinated or the
      nondisinfected samples. To develop correlations between SFI, SUVA, and
      cytotoxicity, we analyzed 21 independent samples. Significant linear correlations
      found among these samples suggest that under the tested conditions, cytotoxicity
      was preferentially influenced by the fluorescence and SUVA of their composite
      organic agents. These two spectroscopic parameters may be used as indicators for
      the potential cytotoxicity of nondisinfected, ozonated, or chlorinated municipal
      wastewaters.

PMID- 29359930
TI  - Large Anisotropy Barrier in a Tetranuclear Single-Molecule Magnet Featuring Low
      Coordinate Cobalt Centers.
AB  - The tetranuclear cobalt cluster compound [Co4(MU-NPtBu3)4][B(C6F5)4] (tBu = tert
      butyl) was synthesized by chemical oxidation of Co4(NPtBu3)4 with
      [FeCp2][B(C6F5)4] and magnetically characterized to study the effect of
      electronic communication between low-coordinate metal centers on slow magnetic
      relaxation in a transition metal cluster. The dc magnetic susceptibility data
      reveal that the complex exhibits a well-isolated S = 9/2 ground state, which
      persists even to 300 K and is attributed to the existence of direct metal-metal
      orbital overlap. The ac magnetic susceptibility data further reveals that the
      complex exhibits slow magnetic relaxation in the absence of an applied field, and
      that the relaxation dynamics can be fit with a combination of Orbach, quantum
      tunneling, and Raman relaxation processes. The effective spin reversal barrier
      for this molecule is 87 cm-1, the largest reported to date for a transition metal
      cluster, and arises due to the presence of a large easy-axis magnetic anisotropy.
      The complex additionally exhibits waist-restricted magnetic hysteresis and
      magnetic blocking below 3.6 K. Taken together, these results indicate that
      coupling of low-coordinate metal centers is a promising strategy to enhance
      magnetic anisotropy and slow magnetic relaxation in transition metal cluster
      compounds.

PMID- 29359932
TI  - Carbonyl-Phenol Adducts: An Alternative Sink for Reactive and Potentially Toxic
      Lipid Oxidation Products.
AB  - Different from the well-characterized function of phenolics as antioxidants,
      their function as lipid-derived carbonyl scavengers is mostly unknown. However,
      phenolics react with lipid-derived carbonyls as a function of the nucleophilicity
      of their reactive groups and the electronic effects and steric hindrances present
      in the reactive carbonyls. Furthermore, the reaction produces a wide variety of
      carbonyl-phenol adducts, some of which are stable and have been isolated and
      characterized but others polymerize spontaneously. This perspective updates
      present knowledge about the lipid-derived carbonyl trapping ability of phenolics,
      its competition with carbonyl-amine reactions produced in foods, and the presence
      of carbonyl-phenol adducts in food products.

PMID- 29359931
TI  - Self-Sorting of Heteroanions in the Assembly of Cross-Shaped Polyoxometalate
      Clusters.
AB  - Heteroanion (HA) moieties have a key role in templating of heteropolyoxometalate
      (HPA) architectures, but clusters templated by two different templates are rarely
      reported. Herein, we show how a cross-shaped HPA-based architecture can self-sort
      the HA templates by pairing two different guests into a divacant {XYW15O54}
      building block, with four of these building block units being linked together to
      complete the cross-shaped architecture. We exploited this observation to
      incorporate HA templates into well-defined positions within the clusters, leading
      to the isolation of a collection of mixed-HA templated cross-shaped polyanions
      [(XYW15O54)4(WO2)4]32-/36- (X = H-P, Y = Se, Te, As). The template positions have
      been unambiguously determined by single crystal X-ray diffraction, NMR
      spectroscopy, and high-resolution electrospray ionization mass spectrometry;
      these studies demonstrated that the mixed template containing HPA clusters are
      the preferred products which crystallize from the solution. Theoretical studies
      using DFT calculations suggest that the selective self-sorting originates from
      the coordination of the template in solution. The cross-shaped polyoxometalate
      clusters are redox-active, and the ability of molecules to accept electrons is
      slightly modulated by the HA incorporated as shown by differential pulse
      voltammetry experiments. These results indicate that the cross-shaped HPAs can be
      used to select templates from solution, and themselves have interesting
      geometries, which will be useful in developing functional molecular architectures
      based upon HPAs with well-defined structures and electronic properties.

PMID- 29359933
TI  - Understanding and Controlling the Emission Brightness and Color of Molecular
      Cerium Luminophores.
AB  - Molecular cerium complexes are a new class of tunable and energy-efficient
      visible- and UV-luminophores. Understanding and controlling the emission
      brightness and color are important for tailoring them for new and specialized
      applications. Herein, we describe the experimental and computational analyses for
      series of tris(guanidinate) (1-8, Ce{(R2N)C(N iPr)2}3, R = alkyl, silyl, or
      phenyl groups), guanidinate-amide [GA, A = N(SiMe3)2, G = (Me3Si)2NC(N iPr)2],
      and guanidinate-aryloxide (GOAr, OAr = 2,6-di- tert-butylphenoxide) cerium(III)
      complexes to understand and develop predictive capabilities for their optical
      properties. Structural studies performed on complexes 1-8 revealed marked
      differences in the steric encumbrance around the cerium center induced by various
      guanidinate ligand backbone substituents, a property that was correlated to
      photoluminescent quantum yield. Computational studies revealed that consecutive
      replacements of the amide and aryloxide ligands by guanidinate ligand led to less
      nonradiative relaxation of bright excited states and smaller Stokes shifts. The
      results establish a comprehensive structure-luminescence model for molecular
      cerium(III) luminophores in terms of both quantum yields and colors. The results
      provide a clear basis for the design of tunable, molecular, cerium-based,
      luminescent materials.

PMID- 29359935
TI  - A Series of Enthalpically Optimized Docetaxel Analogues Exhibiting Enhanced
      Antitumor Activity and Water Solubility.
AB  - A dual-purpose strategy aimed at enhancing the binding affinity for microtubules
      and improving the water solubility of docetaxel led to the design and synthesis
      of a series of C-2- and C-3'-modified analogues. Both aims were realized when the
      C-3' phenyl group present in docetaxel was replaced with a propargyl alcohol. The
      resulting compound, 3f, was able to overcome drug resistance in cultured P-gp
      overexpressing tumor cells and showed greater activity than docetaxel against
      drug-resistant A2780/AD ovarian cancer xenografts in mice. In addition, the
      considerably lower hydrophobicity of 3f relative to both docetaxel and paclitaxel
      led to better aqueous solubility. A molecular model of tubulin-bound 3f revealed
      novel hydrogen-bonding interactions between the propargyl alcohol and the polar
      environment provided by the side chains of Ser236, Glu27, and Arg320.

PMID- 29359934
TI  - Chitinase Chi1 from Myceliophthora thermophila C1, a Thermostable Enzyme for
      Chitin and Chitosan Depolymerization.
AB  - A thermostable Chitinase Chi1 from Myceliophthora thermophila C1 was homologously
      produced and characterized. Chitinase Chi1 shows high thermostability at 40 
      degrees C (>140 h 90% activity), 50  degrees C (>168 h 90% activity), and 55 
      degrees C (half-life 48 h). Chitinase Chi1 has broad substrate specificity and
      converts chitin, chitosan, modified chitosan, and chitin oligosaccharides. The
      activity of Chitinase Chi1 is strongly affected by the degree of deacetylation
      (DDA), molecular weight (Mw), and side chain modification of chitosan. Chitinase
      Chi1 releases mainly (GlcNAc)2 from insoluble chitin and chito-oligosaccharides
      with a polymerization degree (DP) ranging from 2 to 12 from chitosan, in a
      processive way. Chitinase Chi1 shows higher activity toward chitin
      oligosaccharides (GlcNAc)4-6 than toward (GlcNAc)3 and is inactive for (GlcNAc)2.
      During hydrolysis, oligosaccharides bind at subsites -2 to +2 in the enzyme's
      active site. Chitinase Chi1 can be used for chitin valorisation and for
      production of chitin- and chito-oligosaccharides at industrial scale.

PMID- 29359936
TI  - Multiplex Infrared Spectroscopy Imaging for Monitoring Spatially Resolved Redox
      Chemistry.
AB  - IR spectroscopy is an excellent method for understanding surface redox chemistry.
      However, obtaining sufficient spatial resolution to analyze in situ surface redox
      reactions is difficult because the aqueous sampling environments provide some
      challenges for IR spectroscopy. These challenges arise because of the vibrational
      contribution of water. In this letter, we demonstrate a solution to this problem,
      where the key development enabling the coupling of spectromicroscopy with
      electrochemical measurements is a CaF2/electrolyte/Au sandwich IR-sensitive
      sample holder that acts as an electrochemical cell. In this system, there is a
      very thin layer of aqueous electrolyte (~10 MUm), and it is possible to monitor,
      in real time, the vibrational maps and changes to the Au surface modified with
      iron(II, III) hexacyanoferrate(II, III) by varying the electrochemical potential.
      By selecting specific vibrational modes with a focal plane array detector, which
      allows the simultaneous collection of IR spectra from 4096 microscopic regions,
      chemical maps showing the surface changes were obtained and analyzed using color,
      providing new insights into how the charge transfer processes affect the chemical
      composition in specific 2D spatially resolved regions.

PMID- 29359937
TI  - Cu Nanoclusters-Encapsulated Liposomes: Toward Sensitive Liposomal
      Photoelectrochemical Immunoassay.
AB  - Herein we report the strategy of liposome-mediated Cu2+-induced exciton trapping
      upon CdS quantum dots (QDs) for amplified photoelectrochemical (PEC) bioanalysis
      application. Specifically, the Cu nanoclusters (NCs)-encapsulated liposomes were
      first fabricated and then processed with antibodies bound to their external
      surfaces. After the sandwich immunocomplexing, the confined liposomal labels were
      subjected to sequential lysis treatments for the release of Cu NCs and numerous
      Cu2+ ions, which were then directed to interact with the CdS QDs electrode. The
      interaction of Cu2+ ions with CdS QDs could generate CuxS and form the trapping
      sites to block the photocurrent generation. Since the photocurrent inhibition is
      closely related with the Cu NCs-loaded liposomal labels, a novel and general
      "signal-off" PEC immunoassay could thus be tailored with high sensitivity.
      Meanwhile, a complementary "signal-on" fluorescent detection could be
      accomplished by measuring the fluorescence intensity originated from the Cu NCs.
      This work features the first use of Cu NCs in PEC bioanalysis and also the first
      NCs-loaded liposomal PEC bioanalysis. More importantly, by using other specific
      ions/reagents-semiconductors interactions, this protocol could serve as a common
      basis for the general development of a new class of liposome-mediated PEC
      bioanalysis.

PMID- 29359938
TI  - Cluster Size and Quinary Structure Determine the Rheological Effects of Antibody
      Self-Association at High Concentrations.
AB  - The question of how nonspecific reversible intermolecular protein interactions
      affect solution rheology at high concentrations is fundamentally rooted in the
      translation of nanometer-scale interactions into macroscopic properties. Well
      defined solutions of purified monoclonal antibodies (mAbs) provide a useful
      system with which to investigate the manifold intricacies of weak protein
      interactions at high concentrations. Recently, characterization of self
      associating IgG1 antibody (mAb2) solutions has established the direct role of
      protein clusters on concentrated mAb rheology. Expanding on our earlier work with
      three additional mAbs (mAb1, mAb3, and mAb4), the observed concentration
      dependent static light scattering and rheological data present a substantially
      more complex relationship between protein interactions and solution viscosity at
      high concentrations. The four mAb systems exhibited divergent correlations
      between cluster formation (size) and concentrated solution viscosities dependent
      on mAb primary sequence and solution conditions. To address this challenge, well
      established features of colloidal cluster phenomena could be applied as a
      framework for interpreting our observations. The initial stages of mAb cluster
      formation were investigated with small-angle X-ray scattering (SAXS) and ensemble
      optimized fit methods, to uncover shifts in the dimer structure populations which
      are produced by changes in mAb interaction modes and association valence under
      the different solution conditions. Analysis of mAb average cluster number and
      effective hydrodynamic radii at high concentrations revealed cluster
      architectures can have a wide range of fractal dimensions. Collectively, the
      static light scattering, SAXS, and rheological characterization demonstrate that
      nonspecific and anisotropic attractive intermolecular interactions produce
      antibody clusters with different quinary structures to regulate the rheological
      properties of concentrated mAb solutions.

PMID- 29359939
TI  - Strong Hydrogen Bonds at the Interface between Proton-Donating and -Accepting
      Self-Assembled Monolayers on Au(111).
AB  - Hydrogen-bonding heterogeneous bilayers on substrates have been studied as a base
      for new functions of molecular adlayers by means of atomic force microscopy
      (AFM), X-ray photoelectron spectroscopy (XPS), infrared reflection absorption
      spectroscopy (IRAS), and density functional theory (DFT) calculations. Here, we
      report the formation of the catechol-fused bis(methylthio)tetrathiafulvalene
      (H2Cat-BMT-TTF) adlayer hydrogen bonding with an imidazole-terminated
      alkanethiolate self-assembled monolayer (Im-SAM) on Au(111). The heterogeneous
      bilayer is realized by sequential two-step immersions in solutions for the
      individual Im-SAM and H2Cat-BMT-TTF adlayer formations. In the measurements by
      AFM, a grained H2Cat-BMT-TTF adlayer on Im-SAM is revealed. The coverage and the
      chemical states of H2Cat-BMT-TTF on Im-SAM are specified by XPS. On the
      vibrational spectrum measured by IRAS, the strong hydrogen bonds between H2Cat
      BMT-TTF and Im-SAM are characterized by the remarkably red-shifted OH stretching
      mode at 3140 cm-1, which is much lower than that for hydrogen-bonding water
      (typically ~3300 cm-1). The OH stretching mode frequency and the adsorption
      strength for the H2Cat-BMT-TTF molecule hydrogen bonding with imidazole groups
      are quantitatively examined on the basis of DFT calculations.

PMID- 29359940
TI  - Emergence of Strong Nonlinear Viscoelastic Response of Semifluorinated Alkane
      Monolayers.
AB  - Viscoelasticity of monolayers of fluorocarbon/hydrocarbon tetrablock amphiphiles
      di(FnHm) ((CnF2n+1CH2)(Cm-2H2m-3)CH-CH(CnF2n+1CH2)(Cm-2H2m-3)) was characterized
      by interfacial dilational rheology under periodic oscillation of the moving
      barriers at the air/water interface. Because the frequency dispersion of the
      response function indicated that di(FnHm) form two-dimensional gels at the
      interface, the viscosity and elasticity of di(FnHm) were first analyzed with the
      classical Kelvin-Voigt model. However, the global shape of stress response
      functions clearly indicated the emergence of a nonlinearity even at very low
      surface pressures (pi ~ 5 mN/m) and small strain amplitudes (u0 = 1%). The
      Fourier-transformed response function of higher harmonics exhibited a clear
      increase in the intensity only from odd modes, corresponding to the nonlinear
      elastic component under reflection because of mirror symmetry. The emergence of
      strong nonlinear viscoelasticity of di(FnHm) at low surface pressures and strain
      amplitudes is highly unique compared to the nonlinear viscoelasticity of other
      surfactant systems reported previously, suggesting a large potential of such
      fluorocarbon/hydrocarbon molecules to modulate the mechanics of interfaces using
      the self-assembled domains of small molecules.

PMID- 29359941
TI  - Evaporation, Lifetime, and Robustness Studies of Liquid Marbles for Collision
      Based Computing.
AB  - Liquid marbles (LMs) have recently attracted interest for use as cargo carriers
      in digital microfluidics and have successfully been implemented as signal
      carriers in collision-based unconventional computing circuits. Both application
      domains require LMs to roll over substantial distances and to survive a certain
      number of collisions without degrading. To evaluate the lifetime of LMs being
      subjected to movement and impact stresses, we have selected four types of coating
      to investigate: polytetrafluoroethylene (PTFE), ultrahigh density polyethylene
      (PE), Ni, and a mixture of Ni with PE (Ni-PE). Hierarchies of robustness have
      been constructed which showed that pure PE LMs survived the longest when
      stationary and in motion. Pure PTFE LMs were shown to be the least resilient to
      multiple impacts. The PTFE coating provided minimal protection against
      evaporative losses for small LM volumes (2 and 5 MUL) however, larger LMs (10
      MUL) were shown to have good evaporative stabilities when stationary. Conversely,
      PE LMs showed a remarkable ability to withstand multiple impacts and were also
      stable when considering just passive evaporation. Hybrid Ni-PE LMs exhibited more
      resilience to multiple impacts compared to Ni LMs. Thus, when designing LM
      devices, it is paramount to determine impact pathways and select appropriate
      coating materials.

PMID- 29359942
TI  - Multiflorumisides A-G, Dimeric Stilbene Glucosides with Rare Coupling Patterns
      from the Roots of Polygonum multiflorum.
AB  - Multiflorumisides A-G (1-7), seven new dimeric stilbene glucosides with two rare
      coupling patterns, were isolated from the roots of Polygonum multiflorum. The
      structures of these new dimeric stilbene glucosides were elucidated through
      comprehensive spectroscopic and chemical analyses. The absolute configurations of
      3 and 5-7 were established by comparing their experimental and quantum-chemical
      ECD data. Putative biosynthetic pathways toward the dimers and their suppressive
      effects against nitric oxide production in lipopolysaccharide-stimulated RAW264.7
      cells are also discussed.

PMID- 29359943
TI  - Bouncing-to-Merging Transition in Drop Impact on Liquid Film: Role of Liquid
      Viscosity.
AB  - When a drop impacts on a liquid surface, it can either bounce back or merge with
      the surface. The outcome affects many industrial processes, in which merging is
      preferred in spray coating to generate a uniform layer and bouncing is desired in
      internal combustion engines to prevent accumulation of the fuel drop on the wall.
      Thus, a good understanding of how to control the impact outcome is highly
      demanded to optimize the performance. For a given liquid, a regime diagram of
      bouncing and merging outcomes can be mapped in the space of Weber number (ratio
      of impact inertia and surface tension) versus film thickness. In addition,
      recognizing that the liquid viscosity is a fundamental fluid property that
      critically affects the impact outcome through viscous dissipation of the impact
      momentum, here we investigate liquids with a wide range of viscosity from 0.7 to
      100 cSt, to assess its effect on the regime diagram. Results show that while the
      regime diagram maintains its general structure, the merging regime becomes
      smaller for more viscous liquids and the retraction merging regime disappears
      when the viscosity is very high. The viscous effects are modeled and subsequently
      the mathematical relations for the transition boundaries are proposed which agree
      well with the experiments. The new expressions account for all the liquid
      properties and impact conditions, thus providing a powerful tool to predict and
      manipulate the outcome when a drop impacts on a liquid film.

PMID- 29359945
TI  - Cell Penetrating Peptide-Based Redox-Sensitive Vaccine Delivery System for
      Subcutaneous Vaccination.
AB  - In immunotherapy, induction of potent cellular immunity by vaccination is
      essential to treat intracellular infectious diseases and tumors. In this work, we
      designed a new synthetic peptide carrier, Cys-Trp-Trp-Arg8-Cys-Arg8-Cys-Arg8-Cys,
      for vaccine delivery by integrating a redox-responsive disulfide bond cross
      linking and cell-penetrating peptide arginine octamer. The carrier peptide bound
      to the antigen protein ovalbumin (OVA) via electrostatic self-assembly to form
      peptide/OVA nanocomposites. Then, the spontaneous oxidization of the thiols of
      the cysteine residues induced interpeptide disulfide bond cross-linking to
      construct denser peptide/OVA condensates. The cell-penetrating peptides
      incorporated in the carrier peptide could increase antigen uptake by antigen
      presenting cells. After being internalized by antigen presenting cells, the
      antigen could be rapidly released in cytoplasm along with degradation of the
      disulfide bonds by intracellular glutathione, which could promote potent CD8+ T
      cell immunity. The cross-linked peptide/OVA condensates were used for
      subcutaneous vaccination. The results showed that the peptide carrier mediated
      potent antigen-specific immune response by significantly increasing IgG titer;
      splenocyte proliferation; the secretion level of cytokines INF-gamma, IL-12, IL
      4, and IL-10; immune memory function, and the activation and maturation of
      dendritic cells. From the results, the low-molecular weight vaccine-condensing
      peptide with definite chemical composition could be developed as a novel class of
      vaccine delivery systems.

PMID- 29359944
TI  - Metabolic Fate of 13C-Labeled Polydextrose and Impact on the Gut Microbiome: A
      Triple-Phase Study in a Colon Simulator.
AB  - The present study introduces a novel triple-phase (liquids, solids, and gases)
      approach, which employed uniformly labeled [U-13C] polydextrose (PDX) for the
      selective profiling of metabolites generated from dietary fiber fermentation in
      an in vitro colon simulator using human fecal inocula. Employing 13C NMR
      spectroscopy, [U-13C] PDX metabolism was observed from colonic digest samples.
      The major 13C-labeled metabolites generated were acetate, butyrate, propionate,
      and valerate. In addition to these short-chain fatty acids (SCFAs), 13C-labeled
      lactate, formate, succinate, and ethanol were detected in the colon simulator
      samples. Metabolite formation and PDX substrate degradation were examined
      comprehensively over time (24 and 48 h). Correlation analysis between 13C NMR
      spectra and gas production confirmed the anaerobic fermentation of PDX to SCFAs.
      In addition, 16S rRNA gene analysis showed that the level of Erysipelotrichaceae
      was influenced by PDX supplementation and Erysipelotrichaceae level was
      statistically correlated with SCFA formation. Overall, our study demonstrates a
      novel approach to link substrate fermentation and microbial function directly in
      a simulated colonic environment.

PMID- 29359946
TI  - Retraction: Pancreatic neuroendocrine tumors. Prognostic factors.

PMID- 29359947
TI  - Recent development in the application of alternative sterilization technologies
      to prepared dishes: A review.
AB  - Sterilization is one of the most effective food preservation methods.
      Conventional thermal sterilization commonly used in food industry usually causes
      the deterioration of food quality. Flavor, aroma, and texture, among other
      attributes, are significantly affected by thermal sterilization. However, demands
      of consumers for nutritious and safe dishes with a minimum change in their
      original textural and sensory properties are growing rapidly. In order to meet
      these demands, new approaches have been explored in the last few years to extend
      the shelf-life of dishes. This review discusses advantages and disadvantages of
      currently available physical sterilization technologies, including irradiation
      (eg. Gamma rays, X-rays, e-beams), microwave and radio frequency when used in
      prepared dishes. The preservation effect of these technologies on prepared dishes
      are normally evaluated by microbiological and sensory analyses.

PMID- 29359948
TI  - Statutory Regulation of Traditional Medicine Practitioners and Practices: The
      Need for Distinct Policy Making Guidelines.
AB  - The World Health Organization (WHO) has called for the increased statutory
      regulation of traditional and complementary medicine practitioners and practices,
      currently implemented in about half of nations surveyed. According to recent WHO
      data, however, the absence of policy guidelines in this area represents a
      significant barrier to implementation of such professional regulations. This
      commentary reviews several key challenges that distinguish the statutory
      regulation of traditional medicine practitioners and practices from biomedical
      professional regulation, providing a foundation for the development of policy
      making parameters in this area. Foremost in this regard are the ongoing impacts
      of the European colonial encounter, which reinforce biomedicine's
      disproportionate political dominance across the globe despite traditional
      medicine's ongoing widespread use (particularly in the global South). In this
      light, the authors discuss the conceptual and historical underpinnings of
      contemporary professional regulatory structures, the tensions between
      institutional and informal traditional medicine training pathways, and the policy
      challenges presented by the prospect of standardizing internally diverse
      indigenous healing approaches. Epistemic and evidentiary tensions, as well as the
      policy complexities surrounding the intersection of cultural and clinical
      considerations, present additional challenges to regulators. Conceptualizing
      professional regulation as an intellectual property claim under the law, the
      authors further consider what it means to protect traditional knowledge and
      prevent misappropriation in this context. Overall, the authors propose that
      innovative professional regulatory approaches are needed in this area to address
      safety, quality of care, and accessibility as key public interest concerns, while
      prioritizing the redress of historical inequities, protection of diverse
      indigenous knowledges, and delivery of care to underserved populations.

PMID- 29359949
TI  - Comparison of peritumoral stromal tissue stiffness obtained by shear wave
      elastography between benign and malignant breast lesions.
AB  - Background Aggressive breast cancers produce abnormal peritumoral stiff areas,
      which can differ between benign and malignant lesions and between different
      subtypes of breast cancer. Purpose To compare the tissue stiffness of the inner
      tumor, tumor border, and peritumoral stroma (PS) between benign and malignant
      breast masses by shear wave elastography (SWE). Material and Methods We enrolled
      133 consecutive patients who underwent preoperative SWE. Using OsiriX commercial
      software, we generated multiple 2-mm regions of interest (ROIs) in a linear
      arrangement on the inner tumor, tumor border, and PS. We obtained the mean
      elasticity value (Emean) of each ROI, and compared the Emean between benign and
      malignant tumors. Odds ratios (ORs) for prediction of malignancy were calculated.
      Subgroup analyses were performed among tumor subtypes. Results There were 85
      malignant and 48 benign masses. The Emean of the tumor border and PS were
      significantly different between benign and malignant masses ( P < 0.05 for all).
      ORs for malignancy were 1.06, 1.08, 1.05, and 1.04 for stiffness of the tumor
      border, proximal PS, middle PS, and distal PS, respectively ( P < 0.05 for all).
      Malignant masses with a stiff rim were significantly larger than malignant masses
      without a stiff rim, and were more commonly associated with the luminal B and
      triple negative subtypes. Conclusion Stiffness of the tumor border and PS
      obtained by SWE were significantly different between benign and malignant masses.
      Malignant masses with a stiff rim were larger in size and associated with more
      aggressive pathologic subtypes.

PMID- 29359950
TI  - Image quality in coronary computed tomography angiography: influence of adaptive
      statistical iterative reconstruction at various radiation dose levels.
AB  - Background Computed tomography (CT) technology is rapidly evolving and software
      solution developed to optimize image quality and/or lower radiation dose. Purpose
      To investigate the influence of adaptive statistical iterative reconstruction
      (ASIR) at different radiation doses in coronary CT angiography (CCTA) in detailed
      image quality. Material and Methods A total of 160 CCTA were reconstructed as
      follows: 55 scans with filtered back projection (FBP) (650 mA), 51 scans (455 mA)
      with 30% ASIR (ASIR30), and 54 scans (295 mA) with 60% ASIR (ASIR60). For each
      reconstruction, subjective image quality was assessed by five independent
      certified cardiologists using a visual grading analysis (VGA) with five
      predefined image quality criteria consisting of a 5-point scale. Objective
      measures were contrast, noise, and contrast-to-noise ratio (CNR). Results The
      CTDIvol resulted in 10.3 mGy, 7.4 mGy, and 4.6 mGy for FBP, ASIR30, and ASIR60,
      respectively. Homogeneity of the left ventricular lumen was the sole aspect in
      which reconstruction algorithms differed with a decreasing effect for ASIR60
      compared to FBP (estimated odds ratio [OR] = 0.49 [95% confidence interval (CI) =
      0.32-0.76; P = 0.001]). Decreased sharpness and spatial- and low-contrast
      resolutions were observed when using ASIR instead of FBP, but differences were
      not statistically significant. Concerning objective measurements, noise increased
      significantly for ASIR30 (OR = 1.08; 95% CI = 1.02-1.14; P = 0.006) and ASIR60
      (OR = 1.06; 95% CI = 1.01-1.12; P = 0.034) compared to FBP. Conclusion ASIR
      significantly decreased the subjectively assessed homogeneity of the left
      ventricular lumen and increased the objectively measured noise compared to FBP.
      Considering these results, ASIR at a reduced radiation dose should be implemented
      with caution.

PMID- 29359951
TI  - Spinal Manipulative Therapies in Visceral Conditions.

PMID- 29359952
TI  - Pharmacological management of agitation among individuals with moderate to severe
      acquired brain injury: A systematic review.
AB  - OBJECTIVE: To conduct a systematic review examining the effectiveness of
      pharmacological management of agitation among individuals with acquired brain
      injury (ABI). DATA SOURCES: MEDLINE, CINAHL, EMBASE, and PsycINFO databases were
      searched for all relevant articles published in English from 1980 to January
      2016. STUDY SELECTION: Studies were included for analysis all participants had
      moderate to severe ABI, n >= 3, and a pharmacological intervention was provided
      for the treatment of agitation and its effectiveness was assessed. DATA
      EXTRACTION: Data extracted included participant demographics, inclusion and
      exclusion criteria, study design, outcome measure(s), and results. Study quality
      was assessed using the Physiotherapy Evidence Database assessment scale for
      randomized controlled trials (RCTs). A level of evidence was assigned to each
      intervention using a modified Sackett scale. DATA SYNTHESIS: Among 165 retrieved
      studies, 19 met inclusion criteria. The included studies consisted of 6 RCTs and
      13 observational studies. Antipsychotic medications were studied predominately (n
      = 6), followed by anticonvulsants (n = 4) and dopaminergic (n = 4),
      antidepressants (n = 3), and beta-blockers (n = 2). Dopaminergic medications,
      specifically amantadine, had the highest level of evidence (Level 1a). The
      antipsychotic lithium carbonate was shown to be effective but was not recommended
      for use due to high risk of neurotoxicity. CONCLUSIONS: Studies consistently
      demonstrated that pharmacological treatment was effective in reducing agitation
      post ABI; however, there was insufficient information to develop a conclusion due
      to the limited number of studies and overall weakness of evidence for each
      individual medication.

PMID- 29359953
TI  - Energy issues in microwave food processing: A review of developments and the
      enabling potentials of solid-state power delivery.
AB  - The enormous magnitude and variety of microwave applications in household,
      commercial and industrial food processing creates a strong motivation for
      improving the energy efficiency and hence, sustainability of the process. This
      review critically assesses key energy issues associated with microwave food
      processing, focusing on previous energy performance studies, energy performance
      metrics, standards and regulations. Factors affecting energy-efficiency are
      categorised into source, load and source-load matching factors. This highlights
      the need for highly-flexible and controllable power sources capable of receiving
      real-time feedback on load properties, and effecting rapid control actions to
      minimise reflections, heating non-uniformities and other imperfections that lead
      to energy losses. A case is made for the use of solid-state amplifiers as
      alternatives to conventional power sources, magnetrons. By a full-scale techno
      economic analysis, including energy aspects, it is shown that the use of solid
      state amplifiers as replacements to magnetrons is promising, not only from an
      energy and overall technical perspective, but also in terms of economics.

PMID- 29359954
TI  - Dietary lipids with potential to affect satiety: Mechanisms and evidence.
AB  - Dietary fat has been implicated in the rise of obesity due to its energy density,
      palatability and weak effects on satiety. As fat is a major contributor to
      overall energy intake, incorporating fat with satiating properties could
      potentially reduce energy intake. This review outlines the potential mechanisms,
      as far as we know, by which Medium-Chain Triglycerides (MCT), Conjugated Linoleic
      Acid (CLA), Short-Chain Fatty Acids (SCFA), Diacylglycerol (DAG), n-3 PUFA, and
      Small Particle Lipids, exerts their satiating effects. The evidence suggests that
      the lipid with the most potential to enhance satiety is MCT. SCFA can also
      promote satiety, but oral administration has been linked to poor tolerability
      rather than satiety. Data on the appetite effects of CLA is limited but does
      suggest potential. Research comparing these lipids to each other is also lacking
      and should be explored to elucidate which of these 'functional lipids' is the
      most beneficial in enhancing satiety.

PMID- 29359955
TI  - Can dynamic in vitro digestion systems mimic the physiological reality?
AB  - During the last decade, there has been a growing interest in understanding the
      fate of food during digestion in the gastrointestinal tract in order to
      strengthen the possible effects of food on human health. Ideally, food digestion
      should be studied in vivo on humans but this is not always ethically and
      financially possible. Therefore simple static in vitro digestion models mimicking
      the gastrointestinal tract have been proposed as alternatives to in vivo
      experiments but these models are quite basic and hardly recreate the complexity
      of the digestive tract. In contrast, dynamic models that allow pH regulation,
      flow of the food and injection in real time of digestive enzymes in the different
      compartments of the gastrointestinal tract are more promising to accurately mimic
      the digestive process. Most of the systems developed so far have been compared
      for their performances to in vivo data obtained on animals and/or humans. The
      objective of this article is to review the validation towards in vivo data of
      some of the dynamic digestion systems currently available in order to determine
      what aspects of food digestion they are able to mimic. Eight dynamic digestion
      systems are presented as well as their validation towards in vivo data.
      Advantages and limits of each simulator is discussed. This is the result of a
      cooperative international effort made by some of the scientists involved in
      Infogest, an international network on food digestion.

PMID- 29359956
TI  - Nutritional Assessment of the Children of the Beta Israel Community in Ethiopia:
      A 2017 Update.
AB  - BACKGROUND: Malnutrition is a common phenomenon worldwide and a major public
      health problem, particularly in developing poorer countries like Ethiopia.
      Although malnutrition can affect any age group, children are at a higher risk and
      it is associated with an increased morbidity and mortality. The aim of this study
      was to update and assess the nutritional status of children of the Beta Israel
      community in the Gondar area of Ethiopia. METHODS: This was a community-based
      cross-sectional anthropometrical study of all the children of the community age 0
      60 months. A structured questionnaire was used to collect sociodemographic data,
      nutritional history, and clinical parameters. Nutritional indices weight for age,
      height for age, and weight for height were used to define the nutritional status
      of the children. The 2006 World Health Organization (WHO) growth curves served as
      reference parameters. Statistical analysis included binary logistical regression
      analysis. RESULTS: A total of 489 children, representing over 90% of the
      community's children were studied with the mean age and standard deviation of
      36.5 and 18 months, respectively. The overall prevalence of malnutrition was
      found to be 39.1% with wasting, underweight, and stunting occurring in 22.1%,
      26.2%, and 18.4% of the children, respectively. Severe wasting, severe
      underweight, and severe stunting occurred in 8.4%, 8.2% and 5.3% of the children,
      respectively. Multivariate analysis showed that age was significantly associated
      with the occurrence of malnutrition with younger children being at a higher risk
      (p = 0.044). Gender of child, family income, maternal education, presence of
      illness in the month preceding data collection, and household size did not show
      any association with malnutrition prevalence. CONCLUSION: The prevalence of
      malnutrition as measured by stunting, underweight, and wasting has remained high
      among children younger than 5 years of the Beta Israel community in Gondar.
      Moreover, younger children were found to be more malnourished than older
      children.

PMID- 29359957
TI  - Timing of cranioplasty and shunt placement.

PMID- 29359958
TI  - Effect of resveratrol on blood pressure: A systematic review and meta-analysis of
      randomized, controlled, clinical trials.
AB  - INTRODUCTION: Results of previous clinical trials evaluating the effect of
      resveratrol supplementation on blood pressure (BP) are controversial. PURPOSE: We
      aimed to assess the impact of resveratrol on BP through systematic review of
      literature and meta-analysis of available randomized, controlled clinical trials
      (RCTs). METHODS: Literature search included SCOPUS, PubMed-Medline, ISI Web of
      Science and Google Scholar databases up to 17th October 2017 to identify RCTs
      investigating the impact of resveratrol on BP. Two review authors independently
      extracted data on study characteristics, methods and outcomes. Overall, the
      impact of resveratrol on BP was reported in 17 trials. RESULTS: Administration of
      resveratrol did not significantly affect neither systolic BP [weighted mean
      difference (WMD): -2.5 95% CI:(-5.5, 0.6) mmHg; p=0.116; I2=62.1%], nor diastolic
      BP [WMD: -0.5 95% CI:(-2.2, 1.3) mmHg; p=0.613; I2=50.8], nor mean BP [MAP; WMD: 
      1.3 95% CI:(-2.8, 0.1) mmHg; p=0.070; I2=39.5%] nor pulse pressure [PP; WMD: -0.9
      95% CI:(-3.1, 1.4) mmHg; p=0.449; I2=19.2%]. However, significant WMDs were
      detected in subsets of studies categorized according to high resveratrol daily
      dosage (>=300 mg/day) and presence of diabetes. Meta-regression analysis revealed
      a positive association between systolic BP-lowering resveratrol activity (slope:
      1.99; 95% CI: 0.05, 3.93; two-tailed p= 0.04) and Body Mass Index (BMI) at
      baseline, while no association was detected neither between baseline BMI and MAP
      lowering resveratrol activity (slope: 1.35; 95% CI: -0.22, 2.91; two-tailed p=
      0.09) nor between baseline BMI and PP-lowering resveratrol activity (slope: 1.03;
      95% CI: -1.33, 3.39; two-tailed p= 0.39). Resveratrol was fairly well-tolerated
      and no serious adverse events occurred among most of the eligible trials.
      CONCLUSION: The favourable effect of resveratrol emerging from the current meta
      analysis suggests the possible use of this nutraceutical as active compound in
      order to promote cardiovascular health, mostly when used in high daily dose
      (>=300 mg/day) and in diabetic patients.

PMID- 29359959
TI  - The ketogenic diet as a treatment for traumatic brain injury: a scoping review.
AB  - Traumatic brain injury (TBI) is a leading cause of morbidity and mortality
      worldwide. The ketogenic diet (KD) has been identified as a potential therapy to
      enhance recovery after TBI. The purpose of this study is to complete a scoping
      review and synthesize the evidence regarding the KD and its therapeutic effects
      in TBI. The methodological framework of Arksey and O'Malley was employed.
      Databases searched include Medline, EMBASE, CCRCT, CINAHL and WebOfScience. Two
      reviewers independently screened titles, abstracts and full texts in a two-step
      screening protocol to determine inclusion. Abstracted data included study setting
      and therapeutic mechanism. The KD was demonstrated to reduce cerebral oedema,
      apoptosis, improve cerebral metabolism and behavioural outcomes in rodent TBIs.
      Additionally, the KD affected rodent TBIs in an age-dependent manner. Due to a
      lack of relevant outcome measures, the human trials did not establish much
      evidence with respect to the KD as a treatment for TBI; only its safety was
      established. The KD is an effective treatment for TBI recovery in rats and shows
      potential in humans. Future research should aim to better elucidate the KD's
      mechanisms of action in human TBIs and determine if the KD's effectiveness on
      clinical outcomes can be reproduced in humans.

PMID- 29359960
TI  - The ISBER Self-Assessment Tool Indicates Main Pathways for Improvement in
      Biobanks and Supports International Standardization.

PMID- 29359961
TI  - Investigating relationships between ancestry, lifestyle behaviors and perceptions
      of heart disease and breast cancer among Canadian women with British and with
      South Asian ancestry.
AB  - BACKGROUND: Ethnic minority groups including Asians in Canada have different
      knowledge and perceptions of heart disease and breast cancer compared with the
      ethnic majority group. AIM: Examine relationships between perceptions of heart
      disease and breast cancer, and lifestyle behaviors for Canadian women with
      British and with South Asian ancestry. METHODS: Women with South Asian ( n = 170)
      and with British ( n = 373) ancestry ( Mage = 33.01, SD = 12.86) reported leisure
      time physical activity, intended fruit and vegetable consumption, disease
      perceptions (ability to reduce risk, control over getting the diseases, and
      influence of family history), and demographic information. Mann-Whitney tests and
      multiple hierarchical linear regressions were used to examine the relationships
      between lifestyle behaviors and disease perceptions, with ancestry explored as a
      possible moderator. RESULTS: Participants with South Asian ancestry believed they
      had greater ability to reduce their risk and have control over getting breast
      cancer than participants with British ancestry. Family history influences on
      getting either disease was perceived as higher for women with British ancestry.
      Age was positively related to all three perceptions in both diseases. Intended
      fruit and vegetable consumption was positively related to perceptions of ability
      to reduce risk and control of both diseases, but was stronger for women with
      South Asian ancestry regarding perceptions of breast cancer. Leisure time
      physical activity was positively related to perceptions of control over getting
      heart disease for women with British ancestry. CONCLUSIONS: Women's disease
      perceptions can vary by ancestry and lifestyle behaviors. Accurate representation
      of diseases is essential in promoting effective preventative behaviors.

PMID- 29359962
TI  - Enhancing Reuse of Data and Biological Material in Medical Research: From FAIR to
      FAIR-Health.
AB  - The known challenge of underutilization of data and biological material from
      biorepositories as potential resources for medical research has been the focus of
      discussion for over a decade. Recently developed guidelines for improved data
      availability and reusability-entitled FAIR Principles (Findability,
      Accessibility, Interoperability, and Reusability)-are likely to address only
      parts of the problem. In this article, we argue that biological material and data
      should be viewed as a unified resource. This approach would facilitate access to
      complete provenance information, which is a prerequisite for reproducibility and
      meaningful integration of the data. A unified view also allows for optimization
      of long-term storage strategies, as demonstrated in the case of biobanks. We
      propose an extension of the FAIR Principles to include the following additional
      components: (1) quality aspects related to research reproducibility and
      meaningful reuse of the data, (2) incentives to stimulate effective enrichment of
      data sets and biological material collections and its reuse on all levels, and
      (3) privacy-respecting approaches for working with the human material and data.
      These FAIR-Health principles should then be applied to both the biological
      material and data. We also propose the development of common guidelines for cloud
      architectures, due to the unprecedented growth of volume and breadth of medical
      data generation, as well as the associated need to process the data efficiently.

PMID- 29359963
TI  - Melatonin Inhibits the Proliferation of Gastric Cancer Cells Through Regulating
      the miR-16-5p-Smad3 Pathway.
AB  - The incidence and mortality of gastric cancer is steadily increasing annually
      around the world, which required further investigation about alternative therapy
      strategies. Melatonin, an indoleamine synthesized in the pineal gland, has shown
      dramatic anticancer effect in several cancers, however, the function of melatonin
      in gastric cancer needs to be characterized. In this study, we found that
      melatonin inhibited the growth and induced apoptosis of gastric cancer cells.
      microRNAs (miRNAs) have been attractive targets for many anticancer drugs. To
      explore the underlying molecular mechanism by which melatonin attenuated the
      growth of cancer cells, miRNA microarray analysis was performed to screen the
      miRNAs, which significantly altered after melatonin treatment. The result showed
      that melatonin administration enhanced the expression of miR-16-5p. Further
      molecular mechanism research revealed that miR-16-5p targeted Smad3 and
      consequently negatively regulated the abundance of Smad3. Consistently, melatonin
      exposure decreased the level of Smad3 and overexpression of Smad3 attenuated the
      inhibitory effect of melatonin in gastric cancer cells. These results uncovered
      the anticancer effect of melatonin and highlighted the critical roles of miR-16
      5p-Smad3 pathway in melatonin-induced growth defects of gastric cancers.

PMID- 29359964
TI  - miRNA-133a-5p Inhibits the Expression of Osteoblast Differentiation-Associated
      Markers by Targeting the 3' UTR of RUNX2.
AB  - Recent studies have recognized the involvement of microRNAs (miRNAs) in the
      development of osteoporosis, which regulate the balance between osteogenesis and
      osteoclasis. In this study, we investigated the regulation by miRNA-133a-5p on
      the osteoblast differentiation-associated markers in the mouse osteoblast-like
      MC3T3-E1 cells by RUNX2. First, we manipulated the miRNA-133a level in the MC3T3
      E1 cells with 20 or 40 nM miR-133a-5p mimics, miR-133a-5p inhibitor, or scramble
      miRNA. Then, we quantified with real-time polymerase chain reaction (qRT-PCR) the
      expression of Collagen I, osteocalcin (OCN), and osteopontin (OPN) in the miR
      133a-5p-manipulated MC3T3-E1 cells. And the confocal microscopy was also utilized
      to confirm the regulation by miR-133a-5p on the expression of the three
      molecules. We also investigated the extracellular matrix (ECM) mineralization and
      the alkaline phosphatase (ALP) activity in the miR-133a-5p-manipulated MC3T3-E1
      cells. In addition, we explored the possible targeting by miR-133a-5p on RUNX2,
      which was a well-recognized promoter to osteoblast differentiation, with
      luciferase reporter, qRT-PCR, and Western blotting assay. Results demonstrated
      that the miRNA-133a-5p mimics markedly reduced, whereas the miRNA-133a-5p
      inhibitor significantly promoted the expression of Collagen I, OCN, and OPN, the
      ECM mineralization, and the ALP activity in MC3T3-E1 cells. The alignment
      analysis demonstrated a high homology between miRNA-133a-5p and the 3' UTR of
      RUNX2. Moreover, the luciferase reporter assay demonstrated that miRNA-133a-5p
      targeted the 3' UTR of RUNX2, and inhibited the expression of RUNX2 in both mRNA
      and protein levels. In conclusion, we identified the inhibition by miRNA-133a-5p
      to the expression of osteoblast differentiation markers, to the ECM
      mineralization, and to the ALP activity in MC3T3-E1 cells, by targeting the 3'
      UTR of RUNX2. Our study suggests that miRNA-133a-5p might be an important target
      to inhibit osteoblast differentiation in osteoporosis.

PMID- 29359965
TI  - Tempol, a superoxide dismutase-mimetic drug, prevents chronic ischemic renal
      injury in two-kidney, one-clip hypertensive rats.
AB  - Tempol, a superoxide dismutase-mimetic drug, has been shown to attenuate radical
      induced damage, exerting beneficial effects in the animal models of oxidative
      stress and hypertension. This study evaluated the effect of Tempol on renal
      structural and functional alterations in two-Kidney, one-Clip hypertensive rats.
      In this study, young male Wistar rats had the left kidney clipped (2K1C), and
      sham-operated animals (Sham) were used as controls. Animals received Tempol
      (1mmol/L in drinking water) or vehicle for 5 weeks. Systolic blood pressure was
      evaluated once a week. At the end of the experimental protocol, the animals were
      placed in metabolic cages to collect urine (24h) and then anesthetized with
      thiopental (70mg/kg i.p.) to collect blood by puncturing the descending aorta for
      biochemical analysis, and the clipped kidney for morphological and
      immunohistochemical analyses. The vasodilator effect of Tempol was evaluated in
      mesenteric arterial bed (MAB) isolated from adult Wistar rats. The chronic
      treatment with Tempol prevented the development of hypertension and the increased
      plasma levels of urea, creatinine, and 8-isoprostane in 2K1C animals. Tempol also
      improved both glomeruli number and kidney volume to normal levels in the
      2K1C+Tempol group. In addition, the treatment prevented the increased collagen
      deposition and immunostaining for renin, caspase-3, and 8-isoprostane in the
      stenotic kidney of 2K1C animals. Moreover, Tempol induced a dose-dependent
      vasodilator response in MAB from Wistar rats. These results suggest that Tempol
      protects the stenotic kidney against chronic ischemic renal injury and prevents
      renal dysfunction in the 2K1C model, probably through its antioxidant,
      vasodilator and antihypertensive actions.

PMID- 29359966
TI  - "What is the impact of utilizing so-called best practices in percutaneous
      coronary intervention?": an interview with Atul Gupta.
AB  - Atul Gupta, MD speaks to Adam Price-Evans, Managing Commissioning Editor of
      Future Cardiology. Atul Gupta is the Global Chief Medical Officer for the
      business group Image Guided Therapy at Philips, providing medical guidance to
      Philips' clinical vision and strategy. As a practicing interventional and
      diagnostic radiologist, he also serves as a key external clinical voice for Image
      Guided Therapy. His key responsibilities include supporting innovation and
      product development in cardiology, peripheral vascular, surgical, oncology
      interventions, clinical education, office-based labs, medical affairs and new
      business development and ventures. He went to medical school and completed his
      postgraduate training in diagnostic radiology and a fellowship in interventional
      radiology. He maintains a clinical practice, performing interventional and
      diagnostic radiology in both hospital and office-based lab settings.

PMID- 29359967
TI  - Is Searching for Martian Life a Priority for the Mars Community?

PMID- 29359968
TI  - In vitro effects of doxorubicin and tetrathiomolybdate on canine hemangiosarcoma
      cells.
AB  - OBJECTIVE To assess the in vitro effects of doxorubicin and tetrathiomolybdate
      (TM) on cells from a canine hemangiosarcoma cell line. SAMPLE Cultured cells from
      the canine hemangiosarcoma-derived cell line DEN-HSA. PROCEDURES Cells were
      treated with TM (0 to 1.5MUM), doxorubicin (0 to 5MUM), or both with or without
      24 hours of pretreatment with ascorbic acid (750MUM). Degree of cellular
      cytotoxicity was measured with a colorimetric assay. Long-term growth inhibition
      was assessed with a 10-day colony-formation assay. Induction of apoptosis was
      quantitated by fluorometric assessment of caspase-3 and -7 activation. Formation
      of reactive oxygen species (ROS) was also detected fluorometrically. RESULTS
      Exposure of cells to the combination of TM and doxorubicin resulted in a greater
      decrease in proliferation and clonogenic survival rates than exposure to each
      drug alone. This treatment combination increased ROS formation and apoptosis to a
      greater extent than did doxorubicin or TM alone. Ascorbic acid inhibited both TM
      induced ROS formation and apoptosis. CONCLUSIONS AND CLINICAL RELEVANCE Results
      suggested that the enhancement in cytotoxic effects observed with DEN-HSA cell
      exposure to the combination of doxorubicin and TM was achieved through an
      increase in ROS production. These findings provide a rationale for a clinical
      trial of this treatment combination in dogs with hemangiosarcoma.

PMID- 29359969
TI  - Effects of two fractions of inspired oxygen during anesthesia on early
      postanesthesia oxygenation in healthy dogs.
AB  - OBJECTIVE To evaluate the effects of 2 fractions of inspired oxygen (Fio2s)
      during anesthesia on postanesthesia Pao2 and other measures of oxygen exchange.
      ANIMALS 22 healthy adult sexually intact female dogs undergoing
      ovariohysterectomy by ventral midline celiotomy. PROCEDURES Dogs were randomly
      assigned to receive either oxygen (Fio2 > 0.9 [100% oxygen]; n = 11; control
      group) or a mixture of nitrogen and oxygen (Fio2 = 0.4; 11; 40% oxygen group) as
      the carrier gas for isoflurane while anesthetized. All dogs were allowed to
      breathe spontaneously while anesthetized. For each dog, the Pao2, Paco2, other
      indices of oxygenation, and extent of sedation were monitored at predetermined
      times during and for 1 hour after anesthesia. Measured variables were compared
      between the 2 treatment groups and over time within each treatment group. RESULTS
      None of the measured variables differed significantly between the control and 40%
      oxygen groups at any time during the postanesthesia period. Within each treatment
      group, the Paco2 and extent of sedation decreased over time during the
      postanesthesia period. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that
      indices of oxygenation did not differ significantly between healthy dogs in which
      the Fio2 was maintained at > 0.9 and those in which the Fio2 was maintained at
      0.4 while anesthetized for ovariohysterectomy. Thus, the addition of nitrogen to
      the carrier gas for an inhalant anesthetic conferred neither an advantage nor
      disadvantage in regard to oxygenation during the first hour of anesthesia
      recovery.

PMID- 29359970
TI  - Biomechanical evaluation of modified laryngoplasty by use of a toggle technique
      for stabilization of arytenoid cartilage in specimens obtained from equine
      cadavers.
AB  - OBJECTIVE To biomechanically compare modified and standard laryngoplasty
      constructs in monotonic load to failure and cyclic loading. SAMPLES 41 equine
      cadaveric larynges. PROCEDURES Laryngoplasty constructs were created by use of a
      standard technique on one side and a modified technique (with a toggle to anchor
      suture to the arytenoid cartilage) on the other side. For monotonic loading,
      laryngoplasty constructs were prepared and suture ends attached to a load frame;
      constructs then were loaded until mechanical failure. Mean load at failure and
      failure modes were compared between constructs. For cyclic loading, arytenoid
      cartilages were maximally abducted and constructs were circumferentially loaded
      for 10,000 cycles. Loss of arytenoid abduction was evaluated every 500 cycles
      with a subjective grading scale and objective change in rima glottidis cross
      sectional area. RESULTS In monotonic loading, modified laryngoplasty constructs
      failed at a significantly higher mean +/- SD load (191 +/- 29 N) than did
      standard laryngoplasty constructs (91 +/- 44 N). None of the modified
      laryngoplasty constructs failed by suture pull-through of the muscular process of
      the arytenoid cartilage, whereas most of the standard laryngoplasty constructs
      failed in that manner. In cyclic testing, 11 of 20 standard laryngoplasty
      constructs failed or achieved Dixon grade 3 abduction, whereas 0 of 20 modified
      laryngoplasty constructs failed. Modified laryngoplasty constructs lost
      significantly less rima glottidis cross-sectional area in circumferential
      testing, compared with loss for standard laryngoplasty constructs. CONCLUSIONS
      AND CLINICAL RELEVANCE The modified laryngoplasty technique was biomechanically
      superior to the standard laryngoplasty technique in this ex vivo study.

PMID- 29359971
TI  - Immunohistochemical expression of insulin, glucagon, and somatostatin in
      pancreatic islets of horses with and without insulin resistance.
AB  - OBJECTIVE To assess insulin, glucagon, and somatostatin expression within
      pancreatic islets of horses with and without insulin resistance. ANIMALS 10
      insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each
      horse, food was withheld for at least 10 hours before a blood sample was
      collected for determination of serum insulin concentration. Horses with a serum
      insulin concentration < 20 MUU/mL were assigned to the insulin-sensitive group,
      whereas horses with a serum insulin concentration > 20 MUU/mL underwent a
      frequently sampled IV glucose tolerance test to determine sensitivity to insulin
      by minimal model analysis. Horses with a sensitivity to insulin < 1.0 * 10-4
      L*min-1*mU-1 were assigned to the insulin-resistant group. All horses were
      euthanized with a barbiturate overdose, and pancreatic specimens were harvested
      and immunohistochemically stained for determination of insulin, glucagon, and
      somatostatin expression in pancreatic islets. Islet hormone expression was
      compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells
      expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%,
      and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and
      64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive
      horses. Expression of insulin and somatostatin did not differ between insulin
      resistant and insulin-sensitive horses, but the median percentage of glucagon
      expressing cells in the islets of insulin-resistant horses was significantly less
      than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results
      suggested that, in insulin-resistant horses, insulin secretion was not increased
      but glucagon production might be downregulated as a compensatory response to
      hyperinsulinemia.

PMID- 29359972
TI  - Effects of weight loss with a moderate-protein, high-fiber diet on body
      composition, voluntary physical activity, and fecal microbiota of obese cats.
AB  - OBJECTIVE To determine effects of restriction feeding of a moderate-protein, high
      fiber diet on loss of body weight (BW), voluntary physical activity, body
      composition, and fecal microbiota of overweight cats. ANIMALS 8 neutered male
      adult cats. PROCEDURES After BW maintenance for 4 weeks (week 0 = last week of
      baseline period), cats were fed to lose approximately 1.5% of BW/wk for 18 weeks.
      Food intake (daily), BW (twice per week), body condition score (weekly), body
      composition (every 4 weeks), serum biochemical analysis (weeks 0, 1, 2, 4, 8, 12,
      and 16), physical activity (every 6 weeks), and fecal microbiota (weeks 0, 1, 2,
      4, 8, 12, and 16) were assessed. RESULTS BW, body condition score, serum
      triglyceride concentration, and body fat mass and percentage decreased
      significantly over time. Lean mass decreased significantly at weeks 12 and 16.
      Energy required to maintain BW was 14% less than National Research Council
      estimates for overweight cats and 16% more than resting energy requirement
      estimates. Energy required for weight loss was 11% more, 6% less, and 16% less
      than American Animal Hospital Association recommendations for weight loss (80% of
      resting energy requirement) at weeks 1 through 4, 5 through 8, and 9 through 18,
      respectively. Relative abundance of Actinobacteria increased and Bacteroidetes
      decreased with weight loss. CONCLUSIONS AND CLINICAL RELEVANCE Restricted feeding
      of a moderate-protein, high-fiber diet appeared to be a safe and effective means
      for weight loss in cats. Energy requirements for neutered cats may be
      overestimated and should be reconsidered.

PMID- 29359973
TI  - Magnetic resonance imaging evaluation of olfactory bulb angle and soft palate
      dimensions in brachycephalic and nonbrachycephalic dogs.
AB  - OBJECTIVE To determine from MRI measurements whether soft palate length (SPL) and
      thickness are correlated in dogs, evaluate the association between the olfactory
      bulb angle (OBA) and degree of brachycephalia, and determine the correlation
      between soft palate-epiglottis overlap and OBA in dogs. ANIMALS 50 brachycephalic
      and 50 nonbrachycephalic client-owned dogs without abnormalities of the head.
      PROCEDURES Medical records and archived midsagittal T2-weighted MRI images of
      brachycephalic and nonbrachycephalic dogs' heads were reviewed. Group assignment
      was based on breed. Data collected included weight, SPL and thickness, OBA, and
      the distance between the caudal extremity of the soft palate and the basihyoid.
      Soft palate length and thickness were adjusted on the basis of body weight.
      RESULTS Brachycephalic dogs had significantly thicker soft palates and lower
      OBAs, compared with findings for nonbrachycephalic dogs. There was a significant
      negative correlation (r2 = 0.45) between OBA and soft palate thickness. The
      correlation between SPL and OBA was less profound (r2 = 0.09). The distance
      between the caudal extremity of the soft palate and the basihyoid was shorter in
      brachycephalic dogs than in nonbrachycephalic dogs. The percentage of epiglottis
      soft palate overlap significantly decreased with increasing OBA (r2 = 0.31).
      CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that MRI images can be
      consistently used to assess anatomic landmarks for measurement of SPL and
      thickness, OBA, and soft palate-to-epiglottis distance in brachycephalic and
      nonbrachycephalic dogs. The percentage of epiglottis-soft palate overlap was
      significantly greater in brachycephalic dogs and was correlated to the degree of
      brachycephalia.

PMID- 29359974
TI  - Evaluation of self-injurious behavior, food intake, fecal output, and thermal
      withdrawal latencies after injection of a high-concentration buprenorphine
      formulation in rats (Rattus norvegicus).
AB  - OBJECTIVE To evaluate effects of high-concentration buprenorphine (HCB) on self
      injurious behavior, food intake, fecal output, and thermal withdrawal latencies
      in healthy rats. ANIMALS 8 Sprague-Dawley rats. PROCEDURES Rats received 4 SC
      treatments (HCB at 0.075, 0.15, or 0.30 mg/kg [HCB0.075, HCB0.15, and HCB0.30,
      respectively] or 5% dextrose solution [0.20 mL/kg]) in a randomized, crossover
      design study. Self-injurious behavior was assessed for 8 hours after injection.
      Food intake and fecal output were assessed for predetermined periods before and
      after treatment and separated into 12-hour light and dark periods for further
      analysis. Withdrawal latencies were assessed before (time 0) and at predetermined
      times after injection. Data were compared among treatments and time points.
      RESULTS Self-injurious behavior was observed up to 8 hours after injection for
      all HCB, but not dextrose, treatments. Preinjection food intake and fecal output
      amounts were similar among groups and higher during the dark period than during
      the light period. Food intake after all HCB treatments was higher during the
      light period and lower during the dark period, compared with preinjection results
      for the same treatments and with postinjection results for dextrose
      administration. Light-period fecal output was lower after HCB0.15 and HCB0.30
      administration, compared with preinjection values for the same treatments and
      postinjection values for dextrose administration. Percentage change in withdrawal
      latency was significantly higher than that at time 0 (ie, 0%) for only 1
      treatment (HCB0.30) at 1 time point (1 hour after injection). CONCLUSIONS AND
      CLINICAL RELEVANCE Although HCB0.30 produced a degree of thermal hypoalgesia in
      healthy rats, self-injurious behavior and alterations in food intake and fecal
      output were detected, potentially affecting clinical utility of the treatment.

PMID- 29359975
TI  - Perfusion computed tomographic measurements of cerebral blood flow variables in
      live Holstein calves.
AB  - OBJECTIVE To measure cerebral blood flow (CBF) and cerebral blood volume (CBV) by
      means of perfusion CT in clinically normal Holstein calves. ANIMALS 9 Holstein
      calves. PROCEDURES Each of the 9 calves (mean age, 20.2 days) was anesthetized
      and received an injection of iodinated contrast medium into the right jugular
      vein at a rate of 4.0 mL/s. Dynamic CT scanning of the head at a level that
      included the mandibular condyle was initiated at the time of the contrast medium
      injection and continued for 100 seconds. A deconvolution method was used as an
      analytic algorithm. RESULTS Among the 9 calves, the mean +/- SD CBF in the
      cerebral cortex, white matter, and thalamus was 44.3 +/- 10.3 mL/100 g/min, 36.1
      +/- 7.5 mL/100 g/min, and 40.3 +/- 7.5 mL/100 g/min, respectively. The CBF in
      white matter was significantly lower than that in the cerebral cortex or
      thalamus. The mean CBV in the cerebral cortex, white matter, and thalamus was 6.8
      +/- 1.0 mL/100 g, 5.2 +/- 1.0 mL/100 g, and 5.7 +/- 0.7 mL/100 g, respectively.
      The CBV in the cerebral cortex was significantly higher than that in the white
      matter or thalamus. CONCLUSIONS AND CLINICAL RELEVANCE Measurement of CBF and CBV
      in clinically normal calves by means of perfusion CT was feasible. The data
      obtained may be useful as baseline values for use in future research or for
      comparison with findings from calves with CNS diseases. Investigations to
      determine the lower limit of blood flow at which brain function can still be
      restored are warranted.

PMID- 29359976
TI  - Assessment of tissue-specific cortisol activity with regard to degeneration of
      the suspensory ligaments in horses with pituitary pars intermedia dysfunction.
AB  - OBJECTIVE To identify signs of tissue-specific cortisol activity in samples of
      suspensory ligament (SL) and neck skin tissue from horses with and without
      pituitary pars intermedia dysfunction (PPID). SAMPLE Suspensory ligament and neck
      skin tissue samples obtained from 26 euthanized horses with and without PPID.
      PROCEDURES Tissue samples were collected from 12 horses with and 14 horses
      without PPID (controls). Two control horses had received treatment with
      dexamethasone; data from those horses were not used in statistical analyses. The
      other 12 control horses were classified as old horses (>= 14 years old) and young
      horses (<= 9 years old). Standard histologic staining, staining for proteoglycan
      accumulation, and immunostaining of SL and neck skin tissue sections for
      glucocorticoid receptors, insulin, 11beta hydroxysteroid dehydrogenase type 1,
      and 11beta hydroxysteroid dehydrogenase type 2 were performed. Findings for
      horses with PPID were compared with findings for young and old horses without
      PPID. RESULTS Compared with findings for old and young control horses, there were
      significantly more cells stained for glucocorticoid receptors in SL samples and
      for 11 beta hydroxysteroid dehydrogenase type 1 in SL and skin tissue samples
      from horses with PPID. Insulin could not be detected in any of the SL or skin
      tissue samples. Horses with PPID had evidence of SL degeneration with
      significantly increased proteoglycan accumulation. Neck skin tissue was found to
      be significantly thinner in PPID-affected horses than in young control horses.
      CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that tissue-specific
      dysregulation of cortisol metabolism may contribute to the SL degeneration
      associated with PPID in horses.

PMID- 29359977
TI  - Effect of trotting speed on kinematic variables measured by use of extremity
      mounted inertial measurement units in nonlame horses performing controlled
      treadmill exercise.
AB  - OBJECTIVE To assess effects of speed on kinematic variables measured by use of
      extremity-mounted inertial measurement units (IMUs) in nonlame horses performing
      controlled exercise on a treadmill. ANIMALS 10 nonlame horses. PROCEDURES 6 IMUs
      were attached at predetermined locations on 10 nonlame Franches Montagnes horses.
      Data were collected in triplicate during trotting at 3.33 and 3.88 m/s on a high
      speed treadmill. Thirty-three selected kinematic variables were analyzed.
      Repeated-measures ANOVA was used to assess the effect of speed. RESULTS
      Significant differences between the 2 speeds were detected for most temporal
      (11/14) and spatial (12/19) variables. The observed spatial and temporal changes
      would translate into a gait for the higher speed characterized by increased
      stride length, protraction and retraction, flexion and extension, mediolateral
      movement of the tibia, and symmetry, but with similar temporal variables and a
      reduction in stride duration. However, even though the tibia coronal range of
      motion was significantly different between speeds, the high degree of variability
      raised concerns about whether these changes were clinically relevant. For some
      variables, the lower trotting speed apparently was associated with more
      variability than was the higher trotting speed. CONCLUSIONS AND CLINICAL
      RELEVANCE At a higher trotting speed, horses moved in the same manner (eg, the
      temporal events investigated occurred at the same relative time within the
      stride). However, from a spatial perspective, horses moved with greater action of
      the segments evaluated. The detected changes in kinematic variables indicated
      that trotting speed should be controlled or kept constant during gait evaluation.

PMID- 29359978
TI  - Effect of metoclopramide treatment of bitches during the first week of lactation
      on serum prolactin concentration, milk composition, and milk yield and on weight
      gain of their puppies.
AB  - OBJECTIVE To investigate effects of metoclopramide orally administered to healthy
      bitches on serum prolactin and milk lactose concentrations, gross energy, and dry
      matter content and on puppy weight gain during early lactation. ANIMALS 20 client
      owned bitches and their 121 puppies. PROCEDURES 10 bitches received
      metoclopramide (0.2 mg/kg, PO, q 6 h for 6 days; treatment group) starting 10 to
      24 hours after birth of the last puppy of the litter (day 0), and 10 bitches
      served as the control group. Blood and milk samples from all bitches were
      collected on days 0, 1, 2, 4, and 6. Milk samples for days 1 and 2 and days 4 and
      6 were pooled because of small volume. Puppies were weighed twice daily. RESULTS
      Serum prolactin concentration increased significantly over time in both groups,
      and no treatment effect was detected. When day-to-day changes were analyzed, the
      prolactin concentration increased from day 0 to day 1 in the treatment group but
      not in the control group. Milk lactose concentration increased significantly and
      was higher in the treatment group than in the control group. Milk dry matter
      content was unchanged, whereas the time course for milk gross energy content
      differed significantly between treatment and control bitches. Puppy weight gain
      was not affected by metoclopramide treatment. CONCLUSIONS AND CLINICAL RELEVANCE
      Oral administration of metoclopramide to healthy bitches after parturition
      induced a transient increase in serum prolactin concentration and stimulated milk
      lactose production. It is likely bitches with insufficient or delayed milk
      production could benefit from metoclopramide treatment.

PMID- 29359980
TI  - Genome-wide sequencing and quantification of circulating microRNAs for dogs with
      congestive heart failure secondary to myxomatous mitral valve degeneration.
AB  - OBJECTIVE To characterize expression profiles of circulating microRNAs via genome
      wide sequencing for dogs with congestive heart failure (CHF) secondary to
      myxomatous mitral valve degeneration (MMVD). ANIMALS 9 healthy client-owned dogs
      and 8 age-matched client-owned dogs with CHF secondary to MMVD. PROCEDURES Blood
      samples were collected before administering cardiac medications for the
      management of CHF. Isolated microRNAs from plasma were classified into microRNA
      libraries and subjected to next-generation sequencing (NGS) for genome-wide
      sequencing analysis and quantification of circulating microRNAs. Quantitative
      reverse transcription PCR (qRT-PCR) assays were used to validate expression
      profiles of differentially expressed circulating microRNAs identified from NGS
      analysis of dogs with CHF. RESULTS 326 microRNAs were identified with NGS
      analysis. Hierarchical analysis revealed distinct expression patterns of
      circulating microRNAs between healthy dogs and dogs with CHF. Results of qRT-PCR
      assays confirmed upregulation of 4 microRNAs (miR-133, miR-1, miR-let-7e, and miR
      125) and downregulation of 4 selected microRNAs (miR-30c, miR-128, miR-142, and
      miR-423). Results of qRT-PCR assays were highly correlated with NGS data and
      supported the specificity of circulating microRNA expression profiles in dogs
      with CHF secondary to MMVD. CONCLUSIONS AND CLINICAL RELEVANCE These results
      suggested that circulating microRNA expression patterns were unique and could
      serve as molecular biomarkers of CHF in dogs with MMVD.

PMID- 29359982
TI  - Vitamin D deficiency and its relationship with cardiac iron and function in
      patients with transfusion-dependent thalassemia at Chiang Mai University
      Hospital.
AB  - BACKGROUND: Vitamin D deficiency is common in patients with thalassemia. Vitamin
      D deficiency could be related to cardiac dysfunction. Increased parathyroid
      hormone (PTH) is also known to be associated with heart failure. OBJECTIVES: To
      determine the prevalence of Vitamin D deficiency and to explore the impact of
      Vitamin D deficiency on cardiac iron and function in patients with transfusion
      dependent thalassemia. METHOD: A cross-sectional study in patients with
      Transfusion-dependent thalassemia was conducted. Patients with liver disease,
      renal disease, type 1 diabetes, malabsorption, hypercortisolism, malignancy, and
      contraindication for MRI were excluded. Calcium, phosphate, PTH, vitamin D-25OH
      were measured. CardiacT2* and liver iron concentration (LIC) and left ventricular
      ejection fraction (LVEF) were determined. Results Sixty-one (33M/28F) patients
      with Transfusion-dependent thalassemia were enrolled. The prevalence of Vitamin D
      deficiency was 50.8%. Patients with cardiac siderosis had tendency for lower D
      25OH than those without siderosis (15.9 (11.7-20.0) vs. 20.2 (15.85-22.3) ng/mL);
      p = 0.06). Serum calcium, phosphate, PTH, LIC, cardiac T2*, and LVEF were not
      different between the groups with or without Vitamin D deficiency. Patients with
      Vitamin D deficiency had significantly lower hemoglobin levels compared to those
      without Vitamin D deficiency (7.5 (6.93-8.33) vs. 8.1 (7.30-8.50) g/dL; p =
      0.04). The median hemoglobin in the last 12 months was significantly correlated
      with D-25OH. Cardiac T2* had significant correlation with PTH. CONCLUSION:
      Vitamin D deficiency is prevalent in patients with Transfusion-dependent
      thalassemia. Vitamin D level is correlated with hemoglobin level. Vitamin D
      status should be routinely assessed in these patients. Low PTH is correlated with
      increased cardiac iron. This study did not demonstrate an association between
      Vitamin D deficiency and cardiac iron or function in patients with Transfusion
      dependent thalassemia.

PMID- 29359983
TI  - Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved
      and future perspectives.
AB  - INTRODUCTION: Hematopoietic cell transplantation is a potentially lifesaving
      procedure for patients with hematological malignancies who are refractory to
      conventional chemotherapy and/or irradiation treatment. Umbilical cord blood (CB)
      transplantation, as a hematopoietic stem and progenitor cell (HSPC) source, has
      several advantages over bone marrow transplantation with respect to matching and
      prompt availability for transplantation. Additionally, CB has some inherent
      features, such as rapid expansion of T cells, lower prevalence of graft-versus
      host disease and higher graft versus tumor efficacy that make this HSPC cell
      source more favorable over other HSPC sources. Areas covered: This review
      summarizes the current CB and CB derived T cell applications aiming to better
      disease control for hematological malignancies and discusses future directions to
      more effective therapies. Expert commentary: CB transplantation could be used as
      a platform to extract cord blood derived T cells for ex vivo expansion and/or
      gene modification to improve cellular immunotherapies. In addition, combining
      cord blood gene-engineered T cell products with vaccination strategies, such as
      cord blood derived dendritic cell based vaccines, may provide synergistic
      immunotherapies with enhanced anti-tumor effects.

PMID- 29359984
TI  - Current approaches for identifying high-risk non-muscle invasive bladder cancer.
AB  - INTRODUCTION: Management of high risk non-muscle invasive bladder cancer (NMIBC)
      is challenging. It is vital to detect recurrences early and predict which tumors
      are likely to progress. Areas covered: This manuscript reviews the current
      approaches available for detection and surveillance of high risk NMIBCs. A
      literature review was utilized to evaluate risk factors for recurrence and
      progression as well as evaluating approaches including pathological aspects of
      NMIBC, molecular subtyping, methods for tumor visualization, urine cytology,
      urinary molecular markers, molecular tissue markers as well as the scoring
      systems and nomograms. Expert commentary: Clinical and pathological factors are
      still the mainstay of prediction of recurrence and progression. However, genomic
      information such as molecular subtyping may improve understanding of prognosis.
      White light cystoscopy is still a dominant approach but enhanced cystoscopy is
      likely superior for detection of cancer especially carcinoma in situ. Urinary
      biomarkers are evolving; however, they are not ready to replace cystoscopy and
      trials are still necessary to determine optimal clinical utility. Prognostic
      scoring systems and nomograms are available for counseling the patients but there
      is room to improve predictive accuracy.

PMID- 29359985
TI  - Corrigendum.

PMID- 29359986
TI  - A retrospective and prospective look at strategies to increase adolescent HPV
      vaccine uptake in the United States.
AB  - The HPV vaccine debuted more than ten years ago in the United States and many
      strategies have been evaluated to increase HPV vaccination rates, which include
      not only improving current vaccination behaviors but also sustaining these
      behaviors. Researchers and practitioners from a variety of backgrounds have
      engaged in this work, which has included efforts directed at public health and
      government policies, health education and health promotion programs, and clinical
      and patient-provider approaches, as well as work aimed to respond to and combat
      anti-HPV vaccination movements in society. Using a previously developed
      conceptual model to organize and summarize each of these areas, this paper also
      highlights the need for future HPV vaccine promotion work to adopt a multi-level
      and, when possible, integrated approach in order to maximize impact on
      vaccination rates.

PMID- 29359988
TI  - Long-term outcomes following proton therapy for prostate cancer in young men with
      a focus on sexual health.
AB  - BACKGROUND: We investigated long-term outcomes for men <=60 years old treated
      with proton therapy (PT). METHODS: Of 254 men <=60 years old were treated with
      proton therapy alone for prostate cancer. Risk stratification included 56% with
      low-, 42% with intermediate- and 2% with high-risk disease. Patients received 76
      82 Gy at 2 Gy/fraction or 70-72.5 Gy at 2.5 Gy/fraction. Before treatment and
      every 6-12 months for 5 years, patients were evaluated by a physician, answered
      health-related quality of life surveys, including the EPIC, IIEF and IPSS, and
      had PSA evaluated. RESULTS: Median follow-up for the cohort was 7.1 years; 7-year
      biochemical-free survival was 97.8%. Eight men (one high-risk; five intermediate
      risk and two low-risk) experienced biochemical progression, including one who
      died of disease 9 years after treatment. Potency (erections firm enough for
      sexual intercourse) was 90% at baseline and declined to 72% at the first-year
      follow-up, but declined to only 67% at 5 years. Only 2% of patients developed
      urinary incontinence requiring pads. The bowel habits mean score declined from a
      baseline of 96 to 88 at 1 year, which improved over the following years to 93 at
      5 years. CONCLUSIONS: Young men with prostate cancer continue to have excellent
      results with respect to 7-year biochemical control and 5-year erectile function,
      without clinically significant urinary incontinence 5 years after proton therapy.
      Comparative effectiveness studies of proton therapy with surgery and IMRT are
      needed.

PMID- 29359987
TI  - Disparities in Postpartum Contraceptive Counseling and Provision Among Mothers of
      Preterm Infants.
AB  - OBJECTIVE: Use of effective contraception could be one method to decrease
      recurrent preterm birth by increasing intervals between pregnancies. We assessed
      correlates of contraceptive counseling and uptake among women who delivered
      preterm. MATERIALS AND METHODS: This is a retrospective cohort study of women who
      delivered live-born singletons or twins before 32 weeks' gestation. We assessed
      documented contraceptive counseling and method uptake by postpartum discharge,
      using inpatient medical records, and correlates of highly effective contraception
      uptake by the postpartum visit using outpatient records. RESULTS: Of 594 eligible
      women, 44.6% (n = 265) had documented inpatient contraceptive counseling, but
      only 21.4% (n = 127) left the hospital using a World Health Organization (WHO)
      tier 1 or 2 method. Women who were younger, non-Hispanic black, multiparous, and
      delivered at earlier gestational ages were more likely to have inpatient
      counseling documented. Compared with women with private insurance, women with
      public insurance were more likely to have documented counseling (22.8% vs. 87.5%,
      p < 0.001; adjusted odds ratio [aOR] 9.55, 95% confidence interval [CI] 5.31
      17.2) and to uptake a WHO tier 1 or 2 method as an inpatient (5.8% vs. 52.0%, p <
      0.001; aOR 9.51, 95% CI 4.78-18.9). Of the 175 women with outpatient records
      available who attended a postpartum visit, only 54.9% (n = 96) adopted a WHO tier
      1 or tier 2 method. CONCLUSION: Although all women in this cohort were at risk of
      recurrent preterm birth, counseling about contraception after a preterm birth
      (<32 weeks) was not universal. Women with multiple risk factors for recurrent
      preterm birth, such as multiparity and public insurance, were more likely to have
      received documented contraceptive counseling and highly effective contraceptives.

PMID- 29359990
TI  - Dexmedetomidine and Magnesium Sulfate: A Good Combination Treatment for Acute
      Lung Injury?
AB  - OBJECTIVES: In this study, we aimed to investigate the therapeutic effects of
      magnesium sulfate (MgSO4) and dexmedetomidine (dex) in a model of acute lung
      injury (ALI). We determined whether concomitant administration decreased the
      inflammatory effects of hydrochloric acid (HCl)-induced ALI in a synergistic
      manner. MATERIALS AND METHODS: In this study, 42 Sprague-Dawley rats were
      randomized into six groups: Group S (saline), Group SV (saline + mechanical
      ventilation), Group HCl (HCl), Group Dex (Dex), Group Mag (MgSO4), and Group DM
      (Dex + MgSO4). All groups except Group S were mechanically ventilated prior to
      HCl-induced ALI. Saline or HCl was administered via tracheostomy. Prior to
      treatment, HCl was administered to Group HCl, Group Dex, Group Mag, and Group DM
      to induce ALI. Dex and MgSO4 were administered intraperitoneally. The rats were
      monitored for 4 h after treatment to measure oxidative stress parameters in
      blood, and prolidase enzyme activity. Lung tissue damage were determined via
      histopathology. RESULTS: A significant increase in heart rate and rapid
      desaturation was observed in HCl-administered groups. Treatment administration
      decreased the pulse values. Increased saturation values and decreased oxidative
      stress indices were observed in groups that were subsequently administered Dex
      and MgSO4. Serum prolidase activity increased significantly in Group HCl. Severe
      pathological findings were detected following HCl-induced ALI. Group Mag showed
      greater improvement in the pathology of HCl-induced ALI than did Group Dex.
      Administration of both Dex and MgSO4 did not improve the pathological scores.
      CONCLUSIONS: The antioxidant and anti-inflammatory effects of Dex and MgSO4
      ameliorated the detrimental effects of HCI-induced ALI. However, adverse effects
      on hemodynamics and lung damage were observed when the two drugs were
      administered together.

PMID- 29359989
TI  - A role for endothelial cells in radiation-induced inflammation.
AB  - PURPOSE: To unravel the role of the vasculature in radiation-induced brain tissue
      damage. MATERIALS AND METHODS: Postnatal day 14 mice received a single dose of 10
      Gy cranial irradiation and were sacrificed 6 h, 24 h or 7 days post-irradiation.
      Endothelial cells were isolated from the hippocampus and cerebellum using
      fluorescence-activated cell sorting, followed by cell cycle analysis and gene
      expression profiling. RESULTS: Flow cytometric analysis revealed that irradiation
      increased the percentage of endothelial cells, relative to the whole cell
      population in both the hippocampus and the cerebellum. This change in cell
      distribution indicates that other cell types are more susceptible to irradiation
      induced cell death, compared to endothelial cells. This was supported by data
      showing that genes involved in endothelial cell-specific apoptosis (e.g. Smpd1)
      were not induced at any time point investigated but that genes involved in cell
      cycle arrest (e.g. Cdkn1a) were upregulated at all investigated time points,
      indicating endothelial cell repair. Inflammation-related genes, on the other
      hand, were strongly induced, such as Ccl2, Ccl11 and Il6. CONCLUSIONS: We
      conclude that endothelial cells are relatively resistant to ionizing radiation
      but that they play an active, hitherto unknown, role in the inflammatory response
      after irradiation. In the current study, this was shown in both the hippocampus,
      where neurogenesis and extensive cell death after irradiation occurs, and in the
      cerebellum, where neurogenesis no longer occurs at this developmental age.

PMID- 29359991
TI  - Evaluation of alum-based adjuvant on the immunogenicity of salmonella enterica
      serovar typhi conjugates vaccines.
AB  - The function of adjuvant in maintaining the long-term immune response to Typhoid
      conjugate vaccine (TCV) was evaluated in. Two TCV products, Vi-DT and Vi-TT, were
      formulated in either aluminum phosphate (AlPO4) or aluminum hydroxide (AlOH) as
      adjuvants and TCV formulated in phosphate buffer saline were used as controls. In
      each case, a group of Balb/c mice was injected intramuscularly with two doses of
      the formulated vaccine at two-week intervals. The anti-Vi IgG responses were
      monitored by Enzyme-Linked Immunosorbent Assay and the levels of CD4+ T-cells
      expressing cytokine were characterized using intracellular cytokine staining. All
      mice immunized by TCV formulated in adjuvant elicited anti-Vi response to a
      higher level than the group receiving TCV formulated in PBS. The extent of
      adsorption of TCV in AlOH was greater than that in AlPO4, and this finding
      correlated well with the observation that the mice immunized with two doses of Vi
      DT(AlOH) elicited anti-Vi IgG to a level higher than that seen with Vi-DT(AlPO4).
      The mice primed with Vi-TT(AlOH) produced lower anti-Vi IgG (25.901 GM) compared
      to those receiving Vi-TT(AlPO4) (49.219 GM). However, after the second injection,
      the former raised the antibody level significantly to 137.008 GM while the latter
      provided a value of only 104.966 GM. The groups of mice vaccinated by TCV
      formulated in AlOH expressed IL4 at higher levels than the other groups, which
      correlated positively with the high Anti-Vi IgG in these animals. In conclusion,
      AlOH could be recommended as an effective adjuvant for TCV to provide a long-term
      immune response.

PMID- 29359992
TI  - FcgammaRII-binding Centyrins mediate agonism and antibody-dependent cellular
      phagocytosis when fused to an anti-OX40 antibody.
AB  - Immunostimulatory antibodies against the tumor necrosis factor receptors (TNFR)
      are emerging as promising cancer immunotherapies. The agonism activity of such
      antibodies depends on crosslinking to Fc gamma RIIB receptor (FcgammaRIIB) to
      enable the antibody multimerization that drives TNFR activation. Previously, Fc
      engineering was used to enhance the binding of such antibodies to Fcgamma
      receptors. Here, we report the identification of Centyrins as alternative
      scaffold proteins with binding affinities to homologous FcgammaRIIB and
      FcgammaRIIA, but not to other types of Fcgamma receptors. One Centyrin, S29, was
      engineered at distinct positions of an anti-OX40 SF2 antibody to generate
      bispecific and tetravalent molecules named as mAbtyrins. Regardless of the
      position of S29 on the SF2 antibody, SF2-S29 mAbtyrins could bind FcgammaRIIB and
      FcgammaRIIA specifically while maintaining binding to OX40 receptors. In a
      NFkappaB reporter assay, attachment of S29 Centyrin molecules at the C-termini,
      but not the N-termini, resulted in SF2 antibodies with increased agonism owing to
      FcgammaRIIB crosslinking. The mAbtyrins also showed agonism in T-cell activation
      assays with immobilized FcgammaRIIB and FcgammaRIIA, but this activity was
      confined to mAbtyrins with S29 specifically at the C-termini of antibody heavy
      chains. Furthermore, regardless of the position of the molecule, S29 Centyrin
      could equip an otherwise Fc-silent antibody with antibody-dependent cellular
      phagocytosis activity without affecting the antibody's intrinsic antibody
      dependent cell-meditated cytotoxicity and complement-dependent cytotoxicity. In
      summary, the appropriate adoption FcgammaRII-binding Centyrins as functional
      modules represents a novel strategy to engineer therapeutic antibodies with
      improved functionalities.

PMID- 29359993
TI  - The economic and environmental cost of delayed GM crop adoption: The case of
      Australia's GM canola moratorium.
AB  - Incorporating socio-economic considerations (SECs) into national biosafety
      regulations regarding genetically modified (GM) crops have opportunity costs.
      Australia approved the cultivation of GM canola through a science-based risk
      assessment in 2003, but allowed state moratoria to be instituted based on
      potential trade impacts over the period 2004 to 2008 and 2010 in the main canola
      growing states. This analysis constructs a counterfactual assessment using
      Canadian GM canola adoption data to create an S-Curve of adoption in Australia to
      measure the environmental and economic opportunity costs of Australia's SEC-based
      moratoria between 2004 and 2014. The environmental impacts are measured through
      the amount of chemical active ingredients applied during pest management, the
      Environmental Impact Quotient indicator, and greenhouse gas emissions. The
      economic impacts are measured through the variable costs of the weed control
      programs, yield and the contribution margin. The environmental opportunity costs
      from delaying the adoption of GM canola in Australia include an additional 6.5
      million kilograms of active ingredients applied to canola land; a 14.3% increase
      in environmental impact to farmers, consumers and the ecology; 8.7 million litres
      of diesel fuel burned; and an additional 24.2 million kilograms of greenhouse gas
      (GHG) and compound emissions released. The economic opportunity costs of the SEC
      based moratoria resulted in foregone output of 1.1 million metric tonnes of
      canola and a net economic loss to canola farmers' of AU$485.6 million. The paper
      provides some of the first quantified, post-adoption evidence on the opportunity
      cost and environmental impacts of incorporating SECs into GM crop regulation.

PMID- 29359994
TI  - The regulation of host cellular and gut microbial metabolism in the development
      and prevention of colorectal cancer.
AB  - Metabolism regulation is crucial in colorectal cancer (CRC) and has emerged as a
      remarkable field currently. The cellular metabolism of glucose, amino acids and
      lipids in CRC are all reprogrammed. Each of them changes tumour microenvironment,
      modulates bacterial composition and activity, and eventually promotes CRC
      development. Metabolites such as short chain fatty acids, secondary bile acids, N
      nitroso compounds, hydrogen sulphide, polyphenols and toxins like fragilysin,
      FadA, cytolethal distending toxin and colibactin play a dual role in CRC. The
      relationship of gut microbe-metabolite is essential in remodelling intestinal
      microbial ecology composition and metabolic activity. It regulates the metabolism
      of colonic epithelial cells and changes the tumour microenvironment in CRC.
      Microbial metabolism manipulation has been considered to be potentially
      preventive in CRC, but more large-scale clinical trials are required before their
      application in clinical practice in the near future.

PMID- 29359995
TI  - Classification and reporting of severity experienced by animals used in
      scientific procedures: FELASA/ECLAM/ESLAV Working Group report.
AB  - Directive 2010/63/EU introduced requirements for the classification of the
      severity of procedures to be applied during the project authorisation process to
      use animals in scientific procedures and also to report actual severity
      experienced by each animal used in such procedures. These requirements offer
      opportunities during the design, conduct and reporting of procedures to consider
      the adverse effects of procedures and how these can be reduced to minimize the
      welfare consequences for the animals. Better recording and reporting of adverse
      effects should also help in highlighting priorities for refinement of future
      similar procedures and benchmarking good practice. Reporting of actual severity
      should help inform the public of the relative severity of different areas of
      scientific research and, over time, may show trends regarding refinement.
      Consistency of assignment of severity categories across Member States is a key
      requirement, particularly if re-use is considered, or the safeguard clause is to
      be invoked. The examples of severity classification given in Annex VIII are
      limited in number, and have little descriptive power to aid assignment.
      Additionally, the examples given often relate to the procedure and do not attempt
      to assess the outcome, such as adverse effects that may occur. The aim of this
      report is to deliver guidance on the assignment of severity, both prospectively
      and at the end of a procedure. A number of animal models, in current use, have
      been used to illustrate the severity assessment process from inception of the
      project, through monitoring during the course of the procedure to the final
      assessment of actual severity at the end of the procedure (Appendix 1).

PMID- 29359996
TI  - Antenatal care attendance and uptake of skilled delivery, Lokitaung Sub-County
      Hospital, Turkana County, Kenya.
AB  - Globally, nearly 500,000 women die annually from pregnancy- and childbirth
      related complications. Antenatal care (ANC) is one of the most important factors
      in preventing maternal and infant mortality. This study investigated whether ANC
      attendance and sociodemographic characteristics of pregnant women influence
      uptake of skilled delivery at Lokitaung Sub-County Hospital, Turkana County,
      Kenya.

PMID- 29359997
TI  - Scotland's GP paediatric scholarship: an evaluation.
AB  - In a previous publication we described the implementation and early evaluation of
      general practice paediatric scholarships in Scotland. We suggested that it was
      too early to be able to determine whether this significant investment will
      produce a return for Scotland in terms of enhanced roles in providing, leading or
      developing children's services in primary care or at the primary care/secondary
      care interface. This paper presents the results of a survey of the impact of the
      scholarship for the first six cohorts of the scholarship (119 General
      Practitioners). The response rate was 76%. Of the 90 respondents, almost half
      (44) have developed roles or areas of special paediatric interest either within
      or out with the practice, or in three cases both within and out with the
      practice. A total of 37 (43%) of those that continue to work within general
      practice reported that they have developed areas of special interest of benefit
      to the practice. Qualitative analysis of free text questions suggested that
      scholars had benefited from their experience in terms of increased confidence in
      dealing with child health problems, developing links with secondary care
      colleagues, and personal gain with respect to role development. What is already
      known in this area: Changes in GP Training have been suggested in order to
      provide a workforce that can meet the needs of infants, children and young
      people. Studies have shown a positive impact of paediatric trainees and GP
      trainees learning together. Little attention has however been given to the
      potential to support trained GPs to develop their expertise in child health. What
      this work adds: Early evaluation of the Scottish Paediatric Scholarship suggested
      a high degree of satisfaction. This more robust evaluation suggests that almost
      half (44/90 respondents) have developed roles or areas of special paediatric
      interest either within or out with the practice, or in three cases both within
      and out with the practice. Suggestions for future work in this area: A longer
      follow-up supported by more rigorous qualitative evaluation would be beneficial
      in understanding to what extent, and how scholars have played an enhanced role in
      providing, leading or developing children's services in primary care, and what
      role the scholarship has played in realising this. In addition an assessment of
      value for money would be important to ensure that the significant investment in
      the scholarship by NHS Scotland has had demonstrable impact. Ethical statement:
      As an evaluation of a focused CPD programme, ethical approval was not considered
      to be necessary.

PMID- 29359998
TI  - Prolongation of liver-specific function for primary hepatocytes maintenance in 3D
      printed architectures.
AB  - Isolated primary hepatocytes from the liver are very similar to in vivo native
      liver hepatocytes, but they have the disadvantage of a limited lifespan in 2D
      culture. Although a sandwich culture and 3D organoids with mesenchymal stem cells
      (MSCs) as an attractive assistant cell source to extend lifespan can be used, it
      cannot fully reproduce the in vivo architecture. Moreover, long-term 3D culture
      leads to cell death because of hypoxic stress. Therefore, to overcome the
      drawback of 2D and 3D organoids, we try to use a 3D printing technique using
      alginate hydrogels with primary hepatocytes and MSCs. The viability of isolated
      hepatocytes was more than 90%, and the cells remained alive for 7 days without
      morphological changes in the 3D hepatic architecture with MSCs. Compared to a 2D
      system, the expression level of functional hepatic genes and proteins was higher
      for up to 7 days in the 3D hepatic architecture. These results suggest that both
      the 3D bio-printing technique and paracrine molecules secreted by MSCs supported
      long-term culture of hepatocytes without morphological changes. Thus, this
      technique allows for widespread expansion of cells while forming multicellular
      aggregates, may be applied to drug screening and could be an efficient method for
      developing an artificial liver.

PMID- 29360000
TI  - Ambulation and physical function after eccentric resistance training in adults
      with incomplete spinal cord injury: A feasibility study.
AB  - BACKGROUND: Strengthening the lower extremities has shown to positively influence
      walking mechanics in those with neurological deficiencies. Eccentric resistance
      training (ERT) is a potent stimulus for the development of muscular strength with
      low metabolic demand. Thereby, ERT may benefit those with incomplete spinal cord
      injuries (iSCI) seeking to improve ambulatory capacity. DESIGN: This study was
      aimed to determine the effect of ERT on walking speed, mobility, independence,
      and at home function following iSCI. METHODS: Individuals with longstanding iSCI
      trained twice a week for 12 weeks on an eccentrically biased recumbent stepper.
      OUTCOME MEASURES: Walking speed (10 meter walk test; 10MWT), mobility (timed up
      and go), independence (Walking Index for Spinal Cord Injury; WISCI), and at home
      function (Spinal Cord Independence Measure; SCIM) were assessed at baseline,
      after 6 weeks, and after 12 weeks of ERT. RESULTS: There were improvements in
      walking mobility (158.36 + 165.84 seconds to 56.31 + 42.42 seconds, P = .034, d =
      0.62), speed (0.34 + 0.42  m/s to 0.43 + 0.50  m/s, P = .005, d = .23), and
      independence (8 + 7 to 13 + 7, P = .004, d = .73) after 12 weeks of ERT. At home
      function remained unchanged (22 + 10 to 24 + 10, P = .10, d = .12). CONCLUSIONS:
      Improving lower extremity strength translated to walking performance and
      independence in those with iSCI. Additionally, ERT may diminish therapist burden
      in programs designed to improve ambulatory capacity or strength in those with
      iSCI.

PMID- 29360001
TI  - Proposing a three-dimensional, holistic approach to lead the assessment of CPD
      needs.

PMID- 29359999
TI  - Burn Injury-Associated MHCII+ Immune Cell Accumulation Around Lymphatic Vessels
      of the Mesentery and Increased Lymphatic Endothelial Permeability Are Blocked by
      Doxycycline Treatment.
AB  - It is theorized that toxic agents are transported from the hyperpermeable gut of
      burn victims through the lymph, to the systemic circulation, causing global
      injury. We believe that immune cells respond to leakage of "toxic lymph"
      following trauma causing the attraction of these cells to the perilymphatic
      space. To test this, we utilized a model of burn on rats to examine changes in a
      single immune cell population associated with mesenteric lymphatic dysfunction.
      We examined the ability of serum from these animals to increase permeability in
      lymphatic endothelial monolayers and disrupt cellular junctions. We also treated
      burn animals with doxycycline, an inhibitor of microvascular permeability, and
      observed the effects on immune cell populations, morphometry, and lymphatic
      endothelial permeability. Burn injury increased the number of MHCII+ immune cells
      along the vessel (>50%). The size and shape of these cells also changed
      significantly following burn injury. Serum from burn animals increased lymphatic
      endothelial permeability (~1.5-fold) and induced breaks in VE-cadherin staining.
      Doxycycline treatment blocked the accumulation of immune cells along the vessel,
      whereas serum from doxycycline-treated animals failed to increase lymphatic
      endothelial permeability. The size of cells along the vessel in doxycycline
      treated burn animals was not affected, suggesting that the cells already present
      on the lymphatic vessels still respond to substances in the lymph. These findings
      suggest that factors produced during burn can induce lymphatic endothelial
      barrier disruption and lymph produced during traumatic injury can influence the
      attraction and morphology of immune cell populations along the vessel.

PMID- 29360002
TI  - Does acute kidney injury affect survival in adults with acute respiratory
      distress syndrome requiring extracorporeal membrane oxygenation?
AB  - INTRODUCTION: Patients who develop severe acute respiratory distress syndrome
      (ARDS) despite full medical management may require veno-venous extracorporeal
      membrane oxygenation (VV ECMO) to support respiratory function. Survival outcomes
      remain unclear in those who develop acute kidney injury (AKI) requiring
      continuous renal replacement therapy (CRRT) during VV ECMO for isolated severe
      respiratory failure in adult populations. METHODS: A retrospective chart review
      (2010-2016) of patients who underwent VV ECMO for ARDS was conducted with
      university institutional review board (IRB) approval. Patients supported by veno
      arterial ECMO were excluded. AKI was defined by acute renal failure receiving
      CRRT and the outcomes of patients on VV ECMO were compared between the AKI and
      non-AKI groups. RESULTS: We identified 54 ARDS patients supported by VV ECMO
      (mean ECMO days 12 +/- 6.7) with 16 (30%) in the AKI group and 38 (70%) in the
      non-AKI group. No patient had previous renal failure and the serum creatinine was
      not significantly different between the two groups at the time of ECMO
      initiation. The AKI group showed a greater incidence of complications during
      ECMO, including liver failure (38% vs. 5%, p=0.002) and hemorrhage (94% vs. 45%,
      p=0.0008). ECMO survival of the AKI group (56% [9/16]) was inferior to the non
      AKI group (87% [33/38], p=0.014). CONCLUSIONS: Our study demonstrated that VV
      ECMO successfully manages patients with severe isolated lung injury. However,
      once patients develop AKI during VV ECMO, they are likely to further develop
      multi-organ dysfunction, including hepatic and hematological complications,
      leading to inferior survival.

PMID- 29360003
TI  - Evolving therapies for Fuchs' endothelial dystrophy.
AB  - Fuchs' endothelial dystrophy (FED) is characterized by corneal endothelial
      dysfunction and guttate excrescences on the posterior corneal surface, and is the
      leading indication for corneal transplantation in developed countries. In severe
      cases, keratoplasty is considered as the gold standard of treatment. However,
      there have been significant developments in our understanding of FED over the
      past decade. Attempts have been made to treat this disease with regenerative
      therapy techniques such as primary descemetorhexis without an endothelial graft
      or with a tissue-engineering approach. The discovery of a strong association
      between the CTG18.1 trinucleotide repeat expansion sequence and FED may pave the
      way for gene therapy strategies in the future. In this review, we evaluate these
      novel therapeutic modalities as possible alternatives to keratoplasty as the
      standard of care for FED.

PMID- 29360004
TI  - Cholesterol-GalNAc Dual Conjugation Strategy for Reducing Renal Distribution of
      Antisense Oligonucleotides.
AB  - Recently, some studies have reported nephrotoxicity associated with a certain
      class of antisense oligonucleotides (ASOs) in humans. One possibility for
      reducing the potential nephrotoxicity of ASOs is to alter their pharmacokinetics.
      In this study, we investigated the effect of a ligand conjugation strategy on the
      renal accumulation of ASOs. We selected two ligands, cholesterol and N
      acetylgalactosamine (GalNAc), with the purpose of reducing renal distribution and
      liver targeting, and then designed a series of cholesterol-GalNAc dual conjugated
      ASOs. The gene-silencing activity of the cholesterol-GalNAc dual conjugated ASO
      in the liver was slightly lower than that of a GalNAc-conjugated ASO. On the
      other hand, the renal distribution of the cholesterol-GalNAc dual conjugated ASO
      was considerably decreased compared with the GalNAc-conjugated ASO, as we
      expected. As dual conjugation was successful in reducing the renal distribution
      of ASO, it should be an effective strategy for reducing the nephrotoxic potential
      of ASOs.

PMID- 29360005
TI  - Local to Systemic Use of Hypothermia.

PMID- 29360006
TI  - Robotic Versus Laparoscopic Stapler Use for Rectal Transection in Robotic Surgery
      for Cancer.
AB  - BACKGROUND: This study was designed to compare the operative and short-term
      postoperative outcomes of the robotic and laparoscopic staplers in patients
      undergoing rectal surgery for cancer. MATERIALS AND METHODS: Between December
      2014 and April 2017, patients consecutively undergoing robotic rectal surgery for
      cancer were included in this study. Patients were grouped into two according to
      the type of staplers for rectal transection [Robotic (45-mm) versus Laparoscopic
      (60-mm) linear staplers]. Patient demographics, pathologic data, perioperative
      outcomes, and short-term results were compared. RESULTS: One hundred seven
      patients met our inclusion criteria. The number of male patients were higher in
      robotic stapler group than in the laparoscopic stapler group (55% versus 76%, P =
      .03). Age (59 versus 63 years, P = .40), body mass index (27 versus 27 kg/m2, P =
      .60), American Society of Anesthesiologists score (2 versus 2, P = .20), number
      of prior abdominal operations (31% versus 20%, P = .22) and number of patients
      having neoadjuvant chemoradiotherapy (34% versus 36%, P = .86) were comparable
      between the groups. The numbers of cartridges used were similar regardless of the
      type of staplers (2 versus 2, P = .58). The overall complication was similar
      between the groups (24% versus 31%, P = .32). Leak rates were 5% (n = 2) and 3%
      (n = 2) in the robotic and laparoscopic stapler groups, respectively (p = 1).
      There was no mortality. CONCLUSIONS: This is the first study evaluating the role
      of robotic stapler specifically for rectal transection in comparative manner. The
      use of robotic stapler for rectal transection was safe and feasible in rectal
      surgery for cancer.

PMID- 29360007
TI  - Could be serum uric acid a risk factor for thrombosis and/or uveitis in Behcet's
      disease?
AB  - Introduction Serum uric acid level increases in many inflammatory conditions.
      Uric acid triggers the vascular inflammation and artery damage, which causes to
      an increased risk of endothelial dysfunction and atherosclerosis. It is not clear
      in the literature whether uric acid contributes to uveitis by similar mechanisms.
      We investigated whether uric acid level increases in Behcet's disease patients
      with thrombosis or anterior uveitis. Patients and methods We reviewed the medical
      records of 914 Behcet's disease. After screening for exclusion criteria, there
      were 50 Behcet's disease patients with thrombotic complication and as the control
      group 202 BD patients without any vascular complication were included to the
      study. In the Anterior uveitis group, there were 53 Behcet's disease patients.
      The Control group consisted of 39 Behcet's disease patients without eye findings.
      Results Mean uric acid value was 4.96 +/- 1.06 mg/dl in Behcet's disease patients
      with thrombosis whereas 4.08 +/- 0.94 mg/dl in controls, indicating a significant
      difference ( p < 0.001). There was no significant difference between the mean
      ages of the patients in both groups. The mean age of the BD group without eye
      findings was 39.31 +/- 10.47 years and that of the Behcet's disease with Anterior
      Uveitis group was 37.72 +/- 9.65 years ( p = 0.453). The mean serum UA in the BD
      group without eye findings was 4.21 +/- 1.21 mg/dl, while in the BD with Anterior
      Uveitis group it was 4.57 +/- 1.37 mg/dl ( p = 0.201). Conclusion The extent of
      increase in uric acid level was greater in Behcet's disease patients that have a
      thrombotic complication compared to those without thrombotic complication. Uric
      acid seems to play a role in the pathogenesis of thrombosis. It is concluded that
      the elevation of serum uric acid level in patients with anterior uveitis with
      Behcet's disease is not statistically significant.

PMID- 29360009
TI  - Seroprevalence and Risk Factors of Chlamydia abortus Infection in Goats in Hunan
      Province, Subtropical China.
AB  - Chlamydia abortus is an obligate intracellular Gram-negative bacteria, which can
      infect animals and human, including goats. However, little information on C.
      abortus infection is available in goats in Hunan province, subtropical China. To
      investigate the seroprevalence and risk factors of C. abortus infection in goats
      in Hunan province, China, a total of 911 goat blood samples were collected
      randomly from 14 herds having number of goats ranging from 1000 to 3000 from
      March 2014 to December 2015. Seropositive animals were found in 11 out of 14
      (78.57%) goat herds with seroprevalence ranging from 0.00% to 29.94% in
      individual herds. Overall, the seroprevalence of C. abortus infection was
      different among regions (southern Hunan: 1.78%; northeast Hunan: 5.47%; and west
      Hunan: 15.29%), gender (male: 4.58% and female: 9.10%), seasons (spring: 5.97%;
      summer: 2.61%; autumn: 16.88%; and winter: 10.94%), and ages (year <=1: 2.39%; 1
      < year <=2: 9.58%; 2 < year <=3: 9.16%; and year >3: 17.57%). Risk factors for C.
      abortus infection were associated with region, season, and age in this study. To
      our knowledge, this is the first document to demonstrate the existence of C.
      abortus infection in goats, and the seroprevalence was 8.45% out of 911 goats in
      Hunan province.

PMID- 29360010
TI  - Short-term survival after colorectal cancer in a screened versus unscreened
      population.
AB  - AIMS: United States' (US) colorectal cancer (CRC) screening and treatment
      practices seek to reduce mortality. We examined the survival of US patients
      compared with patients in the virtually unscreened Norwegian population. METHODS:
      We compared short-term survival after CRC between the US and Norway using
      relative survival (RS) and excess mortality (EMR) analyses. The CRC patients were
      aged 50 and older diagnosed in the US (Surveillance, Epidemiology and End Results
      registry, 2004, N=9511) and in Norway (Cancer Registry of Norway, 2003-2005,
      N=8256). RESULTS: Death occurred within three years for 39% of the CRC patients.
      Stage distributions were more favorable for US patients. Stage-specific survival
      was similar for localized and regional cancers, but more favorable for US distant
      cancers. In multivariate models of patient, tumor and treatment characteristics,
      patients (especially below age 80) in the US experienced longer survival (EMR
      0.9, CI 0.8-0.9). Stage-specific analyses showed, however, that survival for
      localized cancers was relatively shorter in the US than in Norway (EMR 1.4, CI
      1.1-1.8), but longer for distant cancers (EMR 0.8, CI 0.7-0.8). CONCLUSIONS: The
      enhanced survival for US CRC patients likely reflects a screening-related earlier
      diagnostic stage distribution, as well as prioritized life extension for patients
      with metastatic cancers, reflecting vastly different health care systems in the
      two countries. CRC screening is currently under consideration in Norway. For
      survival outcomes, the current findings do not discourage such an implementation.
      Other screening-related aspects such as feasibility and cost-benefit are,
      however, also relevant and warrant further research within a socialized health
      system.

PMID- 29360011
TI  - Heart valve tissue engineering: an overview of heart valve decellularization
      processes.
AB  - Despite recent advances in medicine and surgery, many people still suffer from
      cardiovascular diseases, which affect their life span and morbidity. Regenerative
      medicine and tissue engineering are novel approaches based on restoring or
      replacing injured tissues and organs with scaffolds, cells and growth factors.
      Scaffolds are acquired from two major sources, synthetic materials and naturally
      derived scaffolds. Biological scaffolds derived from native tissues and cell
      derived matrix offer many advantages. They are more biocompatible with a higher
      affinity to cells, which facilitate tissue reconstruction. Interestingly,
      xenogeneic recipients generally tolerate their components. Therefore, heart valve
      tissue engineering is increasingly benefiting from naturally derived scaffolds.
      In this review, we investigated the different protocols and methods that have
      been used for heart valve decellularization.

PMID- 29360008
TI  - Autologous stem cell therapy for inherited and acquired retinal disease.
AB  - The mammalian retina, derived from neural ectoderm, has little regenerative
      potential. For conditions where irreversible retinal pigment epithelium or
      photoreceptor cell loss occurs, advanced techniques are required to restore
      vision. Inherited retinal dystrophies and some acquired conditions, such as age
      related macular degeneration, have a similar end result of photoreceptor cell
      death leading to debilitating vision loss. These diseases stand to benefit from
      future regenerative medicine as dietary recommendations and current pharmacologic
      therapy only seek to prevent further disease progression. Cell-based strategies,
      such as autologously derived induced pluripotent stem cells, have come a long way
      in overcoming previous technical and ethical concerns. Clinical trials for such
      techniques are already underway. These trials and the preceding preclinical
      studies will be discussed in the context of retinal disease.

PMID- 29360012
TI  - A letter on a hand: Rotating together or separately?
AB  - The motor system plays a role in some object mental rotation tasks, and
      researchers have reported that people may use a strategy of motor simulation to
      mentally rotate objects. In this study, we used images of a hand with a letter
      printed on the palm to directly determine whether a hand image can be
      automatically rotated during the deliberate mental rotation of an object and
      whether the hand and object are rotated in the same trajectory. A total of 41
      participants were shown the stimuli and asked to decide whether the letters,
      which were upright or tilted at specific degrees, were normal or mirrored. The
      hand images in the background showed either a left or a right hand in the palm
      view, with fingers pointing upwards, medial, downwards, or lateral. Reaction
      times and error rates were measured to determine the speed and accuracy of mental
      rotation. A complex interaction between the hand posture and letter orientation
      revealed that the hand image was mentally rotated automatically, together with
      the deliberate mental rotation of the letter. The biomechanical constraints of
      the hand also influenced reaction times, suggesting the involvement of the motor
      system in the concomitant mental rotation of the hand image. Consistent with the
      motor simulation theory, the participants seemed to imagine the hand carrying the
      object in its movement. These behavioural data support the motor simulation
      theory and elucidate specific processes of mental rotation that have not been
      addressed by neuroimaging studies.

PMID- 29360013
TI  - Time of presentation affects auditory distraction: Changing-state and deviant
      sounds disrupt similar working memory processes.
AB  - Four experiments tested conflicting predictions about which components of the
      serial-recall task are most sensitive to auditory distraction. Changing-state
      (Experiments 1a and 1b) and deviant distractor sounds (Experiments 2a and 2b)
      were presented in one of four different intervals of the serial-recall task: (1)
      during the first half of encoding, (2) during the second half of encoding, (3)
      during the first half of retention, or (4) during the second half of retention.
      According to the embedded-processes model, both types of distractors should
      interfere with the encoding and rehearsal of targets in the focus of attention.
      According to the duplex-mechanism account, changing-state distractors should
      interfere only with rehearsal, whereas deviant distractors should interfere only
      with encoding. Inconsistent with the latter view, changing-state and deviant
      distractor sounds interfered with both the encoding and the retention of the
      targets. Both types of auditory distraction were most pronounced during the
      second half of encoding when the increasing rehearsal demands had to be
      coordinated with the continuous updating of the rehearsal set. These findings
      suggest that the two types of distraction disrupt similar working memory
      mechanisms.

PMID- 29360014
TI  - Anticipating the clinical adoption of regenerative medicine: building
      institutional readiness in the UK.
AB  - This perspective paper examines the challenges of implementing regenerative
      medicine (RM) therapies within hospitals and clinics. Drawing on recent work in
      the social sciences, the paper highlights dynamics within existing healthcare
      systems that will present both hindrances and affordances for the implementation
      of new RM technologies within hospitals and clinics. The paper argues that
      identifying suitable locations for cell- and gene-therapy treatment centers
      requires an assessment of their institutional readiness for RM. Some provisional
      criteria for assessing institutional readiness are outlined, and the paper will
      suggest that it is necessary to begin developing a program for the phased
      introduction of RM in the longer term.

PMID- 29360016
TI  - Blow/trauma to the chest and sudden cardiac death: Commotio cordis and contusio
      cordis are leading causes.
AB  - Background In forensic practice, a blow to the chest can lead to sudden cardiac
      death (SCD). Commotio cordis and contusio cordis are leading causes. Methods From
      a database of 4678 patients who suffered from SCD, we found three patients with
      commotio cordis and two patients with contusio cordis. All the patients were
      examined macroscopically and microscopically and had negative toxicology screen.
      Results The three patients who died due to commotio cordis were young males (16,
      23 and 38 years old). The circumstances of death were: a blow to the chest by a
      football, by a friend during a party and during an assault. The hearts were
      completely normal at autopsy. The two patients who had contusio cordis were older
      males (42 and 63 years old). Both patients died during traffic accidents. At
      autopsy, one had significant contusion over the left ventricle, and the second
      had contusion over the right ventricle. Conclusion This study indicates that a
      blow to the chest is very important to document in the circumstances of death,
      and a detailed history is vital. It raises the left ventricular intra-cavitary
      pressure, leading to commotio cordis with immediate death with a normal heart.
      Blunt chest trauma can cause direct myocardial lesions, with acute changes
      leading to contusio cordis.

PMID- 29360015
TI  - Concomitant Regulation by a LacI-Type Transcriptional Repressor XylR on Genes
      Involved in Xylan and Xylose Metabolism and the Type III Secretion System in Rice
      Pathogen Xanthomonas oryzae pv. oryzae.
AB  - The hypersensitive response and pathogenicity (hrp) genes of Xanthomonas oryzae
      pv. oryzae, the causal agent of bacterial leaf blight of rice, encode components
      of the type III secretion system and are essential for virulence. Expression of
      hrp genes is regulated by two key hrp regulators, HrpG and HrpX; HrpG regulates
      hrpX and hrpA, and HrpX regulates the other hrp genes on hrpB-hrpF operons. We
      previously reported the sugar-dependent quantitative regulation of HrpX; the
      regulator highly accumulates in the presence of xylose, followed by high hrp gene
      expression. Here, we found that, in a mutant lacking the LacI-type
      transcriptional regulator XylR, HrpX accumulation and hrp gene expression were
      high even in the medium without xylose, reaching the similar levels present in
      the wild type incubated in the xylose-containing medium. XylR also negatively
      regulated one of two xylose isomerase genes (xylA2 but not xylA1) by binding to
      the motif sequence in the upstream region of the gene. Xylose isomerase is an
      essential enzyme in xylose metabolism and interconverts between xylose and
      xylulose. Our results suggest that, in the presence of xylose, inactivation of
      XylR leads to greater xylan and xylose utilization and, simultaneously, to higher
      accumulation of HrpX, followed by higher hrp gene expression in the bacterium.

PMID- 29360017
TI  - Intravenous rocuronium 0.3 mg/kg improves the conditions for tracheal intubation
      in cats: a randomized, placebo-controlled trial.
AB  - OBJECTIVES: We evaluated the use of rocuronium 0.3 mg/kg intravenously (IV) to
      facilitate tracheal intubation in cats anesthetized for elective
      ovariohysterectomy. METHODS: Thirty female cats were randomly allocated to
      receive rocuronium 0.3 mg/kg IV or an equal volume of normal saline, following
      induction of anesthesia with ketamine and midazolam. Thirty seconds after
      induction, a single investigator, unaware of treatment allocation, attempted
      tracheal intubation. The number of attempts and the time to complete intubation
      were measured. Intubating conditions were assessed as acceptable or unacceptable
      based on a composite score consisting of five different components. Duration of
      apnea after induction was measured and cases of hemoglobin desaturation (SpO2
      <90%) were identified. RESULTS: Intubation was completed faster (rocuronium 12 s
      [range 8-75 s]; saline 60 s [range 9-120 s]) and with fewer attempts (rocuronium
      1 [range 1-2]; saline 2 [range 1-3], both P = 0.006) in cats receiving
      rocuronium. Unacceptable intubating conditions on the first attempt occurred in
      3/15 cats with rocuronium and in 10/15 with saline ( P = 0.01). Apnea lasted 4 +/
      1.6 mins with rocuronium and 2.3 +/- 0.5 mins with saline ( P = 0.0007). No
      cases of desaturation were observed. CONCLUSIONS AND RELEVANCE: Rocuronium 0.3
      mg/kg IV improves intubating conditions compared with saline, and reduces the
      time and number of attempts to intubate with only a short period of apnea in
      cats.

PMID- 29360018
TI  - Investigation on electrical surface modification of waste to energy ash for
      possible use as an electrode material in microbial fuel cells.
AB  - With the world population expected to reach 8.5 billion by 2030, demand for
      access to electricity and clean water will grow at unprecedented rates. Municipal
      solid waste combusted at waste to energy (WtE) facilities decreases waste volume
      and recovers energy, but yields ash as a byproduct, the beneficial uses of which
      are actively being investigated. Ash is intrinsically hydrophobic, highly
      oxidized, and exhibits high melting points and low conductivities. The research
      presented here explores the potential of ash to be used as an electrode material
      for a microbial fuel cell (MFC). This application requires increased conductivity
      and hydrophilicity, and a lowered melting point. Three ash samples were
      investigated. By applying an electric potential in the range 50-125 V across the
      ash in the presence of water, several key property changes were observed: lower
      melting point, a color change within the ash, evidence of changes in surface
      morphologies of ash particles, and completely wetting water-ash contact angles.
      We analyzed this system using a variety of analytical techniques including sector
      field inductively coupled plasma mass spectrometry, scanning electron microscopy,
      X-ray diffraction, differential scanning calorimetry, and tensiometry. Ability to
      make such surface modifications and significant property changes could allow ash
      to become useful in an application such as an electrode material for a MFC.

PMID- 29360019
TI  - Plasmodium parasites of birds have the most AT-rich genes of eukaryotes.
AB  - The genomic architecture of organisms, including nucleotide composition, can be
      highly variable, even among closely-related species. To better understand the
      causes leading to structural variation in genomes, information on distinct and
      diverse genomic features is needed. Malaria parasites are known for encompassing
      a wide range of genomic GC-content and it has long been thought that Plasmodium
      falciparum, the virulent malaria parasite of humans, has the most AT-biased
      eukaryotic genome. Here, I perform comparative genomic analyses of the most AT
      rich eukaryotes sequenced to date, and show that the avian malaria parasites
      Plasmodium gallinaceum, P. ashfordi, and P. relictum have the most extreme coding
      sequences in terms of AT-bias. Their mean GC-content is 21.21, 21.22 and 21.60 %,
      respectively, which is considerably lower than the transcriptome of P. falciparum
      (23.79 %) and other eukaryotes. This information enables a better understanding
      of genome evolution and raises the question of how certain organisms are able to
      prosper despite severe compositional constraints.

PMID- 29360020
TI  - Dentists' Prescribing of Analgesics for Children in British Columbia, Canada
AB  - OBJECTIVE: Recently, there has been great interest in the use, abuse and over
      prescribing of opioid analgesics for children. However, there is a paucity of
      evidence on patterns of prescribing of both narcotic and non-narcotic analgesics
      for children by dentists. METHODS: We used a population-wide prescription drug
      database (PharmaNet) in British Columbia, Canada, to examine prescribing and
      dispensing of analgesics surrounding dental procedures. We examined all drugs
      prescribed for children by dentists between 1997 and 2013, as we had access to
      data on drug doses and days of medication supply. We also examined trends in the
      use of various narcotic and non-narcotic analgesics and benzodiazepines. RESULTS:
      In total, 268 691 children were prescribed at least 1 study drug by a dentist.
      Codeine was the most frequently prescribed: 50% of children received codeine for
      more than 3 days. Duration of use of codeine was greatest among children >=12
      years, the longest duration of use being 5 days. CONCLUSIONS: Our study reveals
      that codeine prescription by dentists increased over the 16-year study period.
      Codeine is prescribed by dentists for 50% of children; prescriptions are for too
      long a duration to avoid potential morphine accumulation and are not in line with
      current treatment guidelines.

PMID- 29360021
TI  - Epidemiologic Investigations into Outbreaks of Rift Valley Fever in Humans, South
      Africa, 2008-2011.
AB  - Rift Valley fever (RVF) is an emerging zoonosis posing a public health threat to
      humans in Africa. During sporadic RVF outbreaks in 2008-2009 and widespread
      epidemics in 2010-2011, 302 laboratory-confirmed human infections, including 25
      deaths (case-fatality rate, 8%) were identified. Incidence peaked in late summer
      to early autumn each year, which coincided with incidence rate patterns in
      livestock. Most case-patients were adults (median age 43 years), men (262; 87%),
      who worked in farming, animal health or meat-related industries (83%). Most case
      patients reported direct contact with animal tissues, blood, or other body fluids
      before onset of illness (89%); mosquitoes likely played a limited role in
      transmission of disease to humans. Close partnership with animal health and
      agriculture sectors allowed early recognition of human cases and appropriate
      preventive health messaging.

PMID- 29360022
TI  - What If a Resident or Medical Student Is Raped? Hospitals' and Academic Medical
      Centers' Title IX Obligations.
AB  - Title IX of the Education Amendments of 1972 protects medical students and
      residents from all forms of sexual discrimination, including sexual harassment
      and assault. Hospitals that train residents as well as medical students must
      follow Title IX mandates, including investigating and addressing all reports of
      sexual discrimination, harassment, or violence. While these processes can help
      eliminate potential barriers to women in medical training, the pressure to
      participate in an internal investigation can discourage some medical students and
      residents from seeking help. Hospitals should work closely with university Title
      IX officials to design and implement effective policies and procedures to both
      prevent and address all types of sexual discrimination as well as to support
      trainees who have been victimized.

PMID- 29360023
TI  - Does Volk v DeMeerleer Conflict with the AMA Code of Medical Ethics on Breaching
      Patient Confidentiality to Protect Third Parties?
AB  - A recent Washington State case revisits the obligation of mental health
      clinicians to protect third parties from the violent acts of their patients.
      Although the case of Volk v DeMeerleer raises multiple legal, ethical, and policy
      issues, this article will focus on a potential ethical conflict between the case
      law and professional guidelines, namely the American Medical Association's Code
      of Medical Ethics.

PMID- 29360024
TI  - Three Perspectives on Mental Health Told through StoryCorps' "Liza Long and
      'Michael'".
AB  - By examining mental illness through the lens of intimate firsthand accounts of
      caregivers and patients, including caregiver blogposts and a conversation between
      Liza Long and her son as recorded by StoryCorps, we demonstrate how new media can
      be leveraged to shift societal perceptions of those with mental illness from
      blameworthy potential perpetrators of terror to vulnerable persons in need of
      compassion and support. Exploring patient, caregiver, and societal roles through
      a close reading of new media firsthand accounts, we argue for shared
      responsibility in caring for those with mental illness and, in particular, for
      physicians to leverage their unique knowledge of the patient experience by
      promoting media coverage of stories of mental illness recovery.

PMID- 29360025
TI  - How Should Physicians Make Decisions about Mandatory Reporting When a Patient
      Might Become Violent?
AB  - Mandatory reporting of persons believed to be at imminent risk for committing
      violence or attempting suicide can pose an ethical dilemma for physicians, who
      might find themselves struggling to balance various conflicting interests. Legal
      statutes dictate general scenarios that require mandatory reporting to supersede
      confidentiality requirements, but physicians must use clinical judgment to
      determine whether and when a particular case meets the requirement. In situations
      in which it is not clear whether reporting is legally required, the situation
      should be analyzed for its benefit to the patient and to public safety. Access to
      firearms can complicate these situations, as firearms are a well-established risk
      factor for violence and suicide yet also a sensitive topic about which physicians
      and patients might have strong personal beliefs.

PMID- 29360026
TI  - Should a Physician Comply with a Parent's Demands for a Forensic Exam on a 16
      Year-Old Trauma Patient?
AB  - Physicians must remain vigilant about their ethical duties to patients,
      especially in high-stakes situations. The question raised by this case-whether a
      physician should comply with a parent's demand for treatment against her underage
      child's wishes-is not one of life or death in which a guardian might more
      credibly argue her judgment should stand. Given that forcing a rape kit exam on a
      patient who refuses to give assent could be further traumatizing, we argue that
      the physician should not comply. Deciding upon a course of action in this
      situation will involve considering what is in the patient's best interest and
      what constitutes a physician's appropriate role in gathering evidence for
      criminal investigations.

PMID- 29360027
TI  - How the Health Sector Can Reduce Violence by Treating It as a Contagion.
AB  - Violence is best understood as an epidemic health problem, and it can be
      effectively prevented and treated using health methods to stop events and
      outbreaks and to reduce its spread. This health framing is important because it
      recognizes that violence is a threat to the health of populations, that exposure
      to violence causes serious health problems, and that violent behavior is
      contagious and can be treated as a contagious process. Relatively standard and
      highly effective health approaches to changing behaviors and norms are
      increasingly being applied to the problem of violence and are showing strong
      evidence of impact among individuals and communities. We need to mobilize our
      nation's health care and public health systems and methods to work with
      communities and other sectors to stop this epidemic.

PMID- 29360028
TI  - Continuing Medical Education and Firearm Violence Counseling.
AB  - Firearm violence is a significant and increasing cause of mortality. Although
      physicians view firearm counseling as their professional obligation, few engage
      in the practice. This study examines medical education and firearm counseling
      among physicians in North Carolina. While 65 percent of physicians reported
      knowing how to counsel patients about gun safety, only 25 percent reported having
      conversations with patients about firearms or firearm safety often or very often.
      Physicians reporting continuing medical education (CME) attendance on gun safety,
      however, were more likely to report providing patients with firearm safety
      counseling and asking patients with depression about firearms. Increasing
      availability of and physician participation in firearm violence prevention CME
      could significantly increase physicians' knowledge of and engagement in firearm
      counseling.

PMID- 29360029
TI  - Law, Ethics, and Conversations between Physicians and Patients about Firearms in
      the Home.
AB  - Firearms in the home pose a risk to household members, including homicide,
      suicide, and unintentional deaths. Medical societies urge clinicians to counsel
      patients about those risks as part of sound medical practice. Depending on the
      circumstances, clinicians might recommend safe firearm storage, temporary removal
      of the firearm from the home, or other measures. Certain state firearm laws,
      however, might present legal and ethical challenges for physicians who counsel
      patients about guns in the home. Specifically, we discuss state background check
      laws for gun transfers, safe gun storage laws, and laws forbidding physicians
      from engaging in certain firearm-related conversations with their patients.
      Medical professionals should be aware of these and other state gun laws but
      should offer anticipatory guidance when clinically appropriate.

PMID- 29360030
TI  - Stop Posturing and Start Problem Solving: A Call for Research to Prevent Gun
      Violence.
AB  - Gun violence is a major cause of preventable injury and death in the United
      States, leading to more than 33,000 deaths each year. However, gun violence
      prevention is an understudied and underfunded area of research. We review the
      barriers to research in the field, including restrictions on federal funding. We
      then outline potential areas in which further research could inform clinical
      practice, public health efforts, and public policy. We also review examples of
      innovative collaborations among interdisciplinary teams working to develop
      strategies to integrate gun violence prevention into patient-doctor interactions
      in order to interrupt the cycle of gun violence.

PMID- 29360031
TI  - What Should Be the Scope of Physicians' Roles in Responding to Gun Violence?
AB  - What role, if any, physicians should have in the response to gun violence is a
      question not only of professionalism but also of law, culture, and ethics. We
      argue that physicians do have important roles to play in the larger landscape of
      advocacy, public opinion, and reduction of gun violence, but that it is not
      ethically or legally appropriate for them to serve as gatekeepers of gun
      privileges by assessing competency.

PMID- 29360032
TI  - Clinicians' Need for an Ecological Approach to Violence Reduction.
AB  - We now know that harmful social policies, such as those that deny health care to
      some people, can generate structural violence and be far more harmful than any
      type of direct violence. A health professional who engages in public health
      promotion must thus consider the adverse effects of structural violence generated
      by bad policies. On this view, the dictum, "first, do no harm," can be
      interpreted as a mandate to protect patients from injustice. Health care
      professionals' responsibilities extend to motivating policies that prevent
      avoidable deaths and disabilities. As we exist within an ecology, we must each
      recognize our responsibility to care for one another and for the larger human
      community.

PMID- 29360033
TI  - Vialation.

PMID- 29360034
TI  - Smiles, Apologies, and Drawing Trauma-Informed Care in the PurpLE Clinic.
AB  - This medical narrative highlights ways in which comics reflect the author's
      experience as a primary care physician striving to offer sensitive care to people
      who have experienced sexual violence.

PMID- 29360035
TI  - Excitatory motor neurons are local oscillators for backward locomotion.
AB  - Cell- or network-driven oscillators underlie motor rhythmicity. The identity of
      C. elegans oscillators remains unknown. Through cell ablation, electrophysiology,
      and calcium imaging, we show: (1) forward and backward locomotion is driven by
      different oscillators; (2) the cholinergic and excitatory A-class motor neurons
      exhibit intrinsic and oscillatory activity that is sufficient to drive backward
      locomotion in the absence of premotor interneurons; (3) the UNC-2 P/Q/N high
      voltage-activated calcium current underlies A motor neuron's oscillation; (4)
      descending premotor interneurons AVA, via an evolutionarily conserved, mixed gap
      junction and chemical synapse configuration, exert state-dependent inhibition and
      potentiation of A motor neuron's intrinsic activity to regulate backward
      locomotion. Thus, motor neurons themselves derive rhythms, which are dually
      regulated by the descending interneurons to control the reversal motor state.
      These and previous findings exemplify compression: essential circuit properties
      are conserved but executed by fewer numbers and layers of neurons in a small
      locomotor network.

PMID- 29360036
TI  - ketu mutant mice uncover an essential meiotic function for the ancient RNA
      helicase YTHDC2.
AB  - Mechanisms regulating mammalian meiotic progression are poorly understood. Here
      we identify mouse YTHDC2 as a critical component. A screen yielded a sterile
      mutant, 'ketu', caused by a Ythdc2 missense mutation. Mutant germ cells enter
      meiosis but proceed prematurely to aberrant metaphase and apoptosis, and display
      defects in transitioning from spermatogonial to meiotic gene expression programs.
      ketu phenocopies mutants lacking MEIOC, a YTHDC2 partner. Consistent with roles
      in post-transcriptional regulation, YTHDC2 is cytoplasmic, has 3'->5' RNA
      helicase activity in vitro, and has similarity within its YTH domain to an N6
      methyladenosine recognition pocket. Orthologs are present throughout metazoans,
      but are diverged in nematodes and, more dramatically, Drosophilidae, where Bgcn
      is descended from a Ythdc2 gene duplication. We also uncover similarity between
      MEIOC and Bam, a Bgcn partner unique to schizophoran flies. We propose that
      regulation of gene expression by YTHDC2-MEIOC is an evolutionarily ancient
      strategy for controlling the germline transition into meiosis.

PMID- 29360037
TI  - Distributed rhythm generators underlie Caenorhabditis elegans forward locomotion.
AB  - Coordinated rhythmic movements are ubiquitous in animal behavior. In many
      organisms, chains of neural oscillators underlie the generation of these rhythms.
      In C. elegans, locomotor wave generation has been poorly understood; in
      particular, it is unclear where in the circuit rhythms are generated, and whether
      there exists more than one such generator. We used optogenetic and ablation
      experiments to probe the nature of rhythm generation in the locomotor circuit. We
      found that multiple sections of forward locomotor circuitry are capable of
      independently generating rhythms. By perturbing different components of the motor
      circuit, we localize the source of secondary rhythms to cholinergic motor neurons
      in the midbody. Using rhythmic optogenetic perturbation, we demonstrate
      bidirectional entrainment of oscillations between different body regions. These
      results show that, as in many other vertebrates and invertebrates, the C. elegans
      motor circuit contains multiple oscillators that coordinate activity to generate
      behavior.

PMID- 29360038
TI  - FoxP2 isoforms delineate spatiotemporal transcriptional networks for vocal
      learning in the zebra finch.
AB  - Human speech is one of the few examples of vocal learning among mammals yet ~half
      of avian species exhibit this ability. Its neurogenetic basis is largely unknown
      beyond a shared requirement for FoxP2 in both humans and zebra finches. We
      manipulated FoxP2 isoforms in Area X, a song-specific region of the avian
      striatopallidum analogous to human anterior striatum, during a critical period
      for song development. We delineate, for the first time, unique contributions of
      each isoform to vocal learning. Weighted gene coexpression network analysis of
      RNA-seq data revealed gene modules correlated to singing, learning, or vocal
      variability. Coexpression related to singing was found in juvenile and adult Area
      X whereas coexpression correlated to learning was unique to juveniles. The
      confluence of learning and singing coexpression in juvenile Area X may underscore
      molecular processes that drive vocal learning in young zebra finches and, by
      analogy, humans.

PMID- 29360039
TI  - Crk proteins transduce FGF signaling to promote lens fiber cell elongation.
AB  - Specific cell shapes are fundamental to the organization and function of
      multicellular organisms. Fibroblast Growth Factor (FGF) signaling induces the
      elongation of lens fiber cells during vertebrate lens development. Nonetheless,
      exactly how this extracellular FGF signal is transmitted to the cytoskeletal
      network has previously not been determined. Here, we show that the Crk family of
      adaptor proteins, Crk and Crkl, are required for mouse lens morphogenesis but not
      differentiation. Genetic ablation and epistasis experiments demonstrated that Crk
      and Crkl play overlapping roles downstream of FGF signaling in order to regulate
      lens fiber cell elongation. Upon FGF stimulation, Crk proteins were found to
      interact with Frs2, Shp2 and Grb2. The loss of Crk proteins was partially
      compensated for by the activation of Ras and Rac signaling. These results reveal
      that Crk proteins are important partners of the Frs2/Shp2/Grb2 complex in
      mediating FGF signaling, specifically promoting cell shape changes.

PMID- 29360041
TI  - Cryptosporidium apodemi sp. n. and Cryptosporidium ditrichi sp. n. (Apicomplexa:
      Cryptosporidiidae) in Apodemus spp.
AB  - Faecal samples from striped field mice (n = 72) and yellow-necked mice (n = 246)
      were screened for Cryptosporidium by microscopy and PCR/sequencing. Phylogenetic
      analysis of small-subunit rRNA, Cryptosporidium oocyst wall protein and actin
      gene sequences revealed the presence of C. parvum, C. hominis, C. muris and two
      new species, C. apodemi and C. ditrichi. Oocysts of C. apodemi are smaller than
      C. ditrichi and both are experimentally infectious for yellow-necked mice but not
      for common voles. Additionally, infection by C. ditrichi was established in one
      of three BALB/c mice. The prepatent period was 7-9 and 5-6 days post infection
      for C. apodemi and C. ditrichi, respectively. The patent period was greater than
      30 days for both species. Infection intensity of C. ditrichi ranged from 4000
      50,000 oocyst per gram of faeces and developmental stages of C. ditrichi were
      detected in the jejunum and ileum. In contrast, neither oocysts nor endogenous
      developmental stages of C. apodemi were detected in faecal or tissue samples,
      although C. apodemi DNA was detected in contents from the small and large
      intestine. Morphological, genetic, and biological data support the establishment
      of C. apodemi and C. ditrichi as a separate species of the genus Cryptosporidium.

PMID- 29360042
TI  - Morphological and molecular characterization of a new succulenticolous Physarum
      (Myxomycetes, Amoebozoa) with unique polygonal spores linked in chains.
AB  - A new plasmodiocarpic and sporocarpic species of myxomycete in the genus Physarum
      is described and illustrated. This new species appeared on decayed leaves and
      remains of succulent plants (Agave, Opuntia, Yucca) growing in arid zones. It
      differs from all other species in the genus in having polyhedral spores linked in
      chains like a string of beads, a unique feature within all known myxomycetes.
      Apart from detailed morphological data, partial sequences of both the small
      subunit ribosomal RNA and elongation factor 1-alpha genes, generated from four
      isolates collected in two distant regions, i.e., Mexico and Canary Islands, are
      also provided in this study. Combined evidence supports the identity of the
      specimens under study as a new species.

PMID- 29360043
TI  - Antiplasmodial and antimalarial activities of quinolone derivatives: An overview.
AB  - Malaria remains one of the most deadly infectious diseases globally. Considering
      the growing spread of resistance, development of new and effective antimalarials
      remains an urgent priority. Quinolones, which are emerged as one of the most
      important class of antibiotics in the treatment of various bacterial infections,
      showed potential in vitro antiplasmodial and in vivo antimalarial activities,
      making them promising candidates for the chemoprophylaxis and treatment of
      malaria. This review presents the current progresses and applications of
      quinolone-based derivatives as potential antimalarials to pave the way for the
      development of new antimalarials.

PMID- 29360040
TI  - Endosomal Rab cycles regulate Parkin-mediated mitophagy.
AB  - Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1,
      gene products mutated in familial Parkinson's disease, play essential roles in
      mitophagy through ubiquitination of mitochondria. Cargo ubiquitination by E3
      ubiquitin ligase Parkin is important to trigger selective autophagy. Although
      autophagy receptors recruit LC3-labeled autophagic membranes onto damaged
      mitochondria, how other essential autophagy units such as ATG9A-integrated
      vesicles are recruited remains unclear. Here, using mammalian cultured cells, we
      demonstrate that RABGEF1, the upstream factor of the endosomal Rab GTPase
      cascade, is recruited to damaged mitochondria via ubiquitin binding downstream of
      Parkin. RABGEF1 directs the downstream Rab proteins, RAB5 and RAB7A, to damaged
      mitochondria, whose associations are further regulated by mitochondrial Rab-GAPs.
      Furthermore, depletion of RAB7A inhibited ATG9A vesicle assembly and subsequent
      encapsulation of the mitochondria by autophagic membranes. These results strongly
      suggest that endosomal Rab cycles on damaged mitochondria are a crucial regulator
      of mitophagy through assembling ATG9A vesicles.

PMID- 29360045
TI  - X-band EPR setup with THz light excitation of Novosibirsk Free Electron Laser:
      Goals, means, useful extras.
AB  - Electron Paramagnetic Resonance (EPR) station at the Novosibirsk Free Electron
      Laser (NovoFEL) user facility is described. It is based on X-band (~9 GHz) EPR
      spectrometer and operates in both Continuous Wave (CW) and Time-Resolved (TR)
      modes, each allowing detection of either direct or indirect influence of high
      power NovoFEL light (THz and mid-IR) on the spin system under study. The optics
      components including two parabolic mirrors, shutters, optical chopper and
      multimodal waveguide allow the light of NovoFEL to be directly fed into the EPR
      resonator. Characteristics of the NovoFEL radiation, the transmission and
      polarization-retaining properties of the waveguide used in EPR experiments are
      presented. The types of proposed experiments accessible using this setup are
      sketched. In most practical cases the high-power radiation applied to the sample
      induces its rapid temperature increase (T-jump), which is best visible in TR
      mode. Although such influence is a by-product of THz radiation, this thermal
      effect is controllable and can deliberately be used to induce and measure
      transient signals of arbitrary samples. The advantage of tunable THz radiation is
      the absence of photo-induced processes in the sample and its high penetration
      ability, allowing fast heating of a large portion of virtually any sample and
      inducing intense transients. Such T-jump TR EPR spectroscopy with THz pulses has
      been previewed for the two test samples, being a useful supplement for the main
      goals of the created setup.

PMID- 29360044
TI  - Development of novel oxazolo[5,4-d]pyrimidines as competitive CB2 neutral
      antagonists based on scaffold hopping.
AB  - A series of novel oxazolo[5,4-d]pyrimidines was designed via a scaffold hopping
      strategy and synthesized through a newly developed approach. All these compounds
      were evaluated for their biological activity toward CB1/CB2 cannabinoid
      receptors, their metabolic stability in mice liver microsomes and their
      cytotoxicity against several cell lines. Eight compounds have been identified as
      CB2 ligands with Ki values less than 1 MUM. It is noteworthy that 2-(2
      chlorophenyl)-5-methyl-7-(4-methylpiperazin-1-yl) oxazolo[5,4-d]pyrimidine 47 and
      2-(2-chlorophenyl)-7-(4-ethylpiperazin-1-yl)- 5-methyloxazolo[5,4-d]pyrimidine 48
      showed CB2 binding affinity in the nanomolar range and significant selectivity
      over CB1 receptors. Interestingly, functionality studies imply that they behave
      as competitive neutral antagonists. Moreover, all tested compounds are devoid of
      cytotoxicity toward several cell lines, including Chinese hamster ovary cells
      (CHO) and human colorectal adenocarcinoma cells HT29.

PMID- 29360046
TI  - Knowledge of performance feedback among boys with ADHD.
AB  - BACKGROUND: Children with attention deficit-hyperactivity disorder (ADHD) often
      experience delays in acquiring competence completing fundamental motor skills.
      The effects of augmented prescriptive knowledge of performance feedback (PKP)
      have not been explored as a possible component solution. AIMS: The purpose of
      this study was to test the motor learning effects of KP among boys with ADHD.
      METHODS AND PROCEDURES: Thirty-one boys with ADHD, randomly selected into either
      a treatment or a control group, completed a series of cornhole games. It was
      hypothesized that PKP feedback administered to treatment group participants would
      increase motor learning. Dependent variables included cornhole scores and quality
      of performance measures. OUTCOMES AND RESULTS: Both groups improved in cornhole
      scores and improvement was not dependent upon KP. Treatment group participants
      performed significantly better in quality of performance of the underhand toss
      compared to the control group. CONCLUSIONS AND IMPLICATIONS: PKP feedback
      improves motor skill performance learning among children with ADHD above
      knowledge of results feedback only. Recreational program directors should
      consider using KP feedback when teaching motor skills to boys with ADHD.

PMID- 29360047
TI  - The effect of caregiver-delivered social-communication interventions on skill
      generalization and maintenance in ASD.
AB  - BACKGROUND: Although caregiver-delivered social communication interventions have
      been considered scientifically proven practices for individuals with autism
      spectrum disorders, it is not well examined if these types of intervention modes
      are truly effective in promoting skill generalization and maintenance within
      those individuals with autism spectrum disorders. AIMS: The purpose of this meta
      analysis was to evaluate the status of the extant literature regarding the
      measures on generalization and/or maintenance of effects of caregiver-delivered
      communication interventions for children with autism spectrum disorders. METHODS
      AND PROCEDURES: This systematic literature review and meta-analysis evaluated
      peer-reviewed research regarding the effects of caregiver-implemented
      interventions on the maintenance and generalization of the social-communication
      skills for children with autism spectrum disorders. A total of 34 articles were
      included following a systematic search. Articles were summarized according to the
      following categories: (a) generalization dimension, (b) generalization assessment
      design, (c) maintenance assessment design, (d) generalization/maintenance
      teaching strategy, and (e) latency to maintenance probes. After application of
      design standards, aggregate Tau-U and non-overlap of pairs effect sizes were
      calculated with a total of 67 separate contrasts across seven studies. OUTCOMES
      AND RESULTS: Overall, effect size scores ranged from small to large effects
      across all comparisons. On average, most of the baseline to maintenance and
      generalization comparisons produced moderate to large effects. Whereas, small to
      moderate or even deteriorate effects were found in most of the intervention to
      maintenance and generalization comparisons. CONCLUSIONS AND IMPLICATIONS: The
      findings in this review suggest that caregiver-delivered social-communication
      interventions are likely to result in mixed effects on skill generalization and
      maintenance within children with autism spectrum disorders. Implications for
      future research and practice are discussed.

PMID- 29360048
TI  - Growth and body composition of preterm infants less than or equal to 32 weeks:
      Cohort study.
AB  - BACKGROUND: Extremely preterm infants with weights less than the 10th percentile
      at discharge have a fat-free mass deficit. AIM: To analyze the relationship of
      weight Z-scores less than -2SD at term age with fat-free mass and fat mass at
      term age and at 1 and 3 months of corrected age in very preterm infants. STUDY
      DESIGN: COHORT STUDY: Subjects: Sixty-six preterm infants born before or at 32
      weeks gestation with birth weight equal or greater than the 10th percentile for
      age were included at term age. They were classified according to weight Z-score
      as either: "term (-)" (n = 18) if weight Z-scores were less -2SD or "term (+)" (n
      = 48) if the weight Z-scores were equal or greater than -2SD at term age. OUTCOME
      MEASURES: Growth and body composition by an air displacement plethysmography
      system and bioimpedance were assessed at term age and 1 and 3 months of corrected
      age. RESULTS: Lower fat-free mass persisted up to 3 months in the "term (-)"
      group [4137 g (645) vs 4592 g (707), p < .01]. Fat mass was lower in the "term (
      )" group at term and at 1 month but was similar at 3 months of corrected age
      [1295 g (774) vs 1477 g (782), p = .109]. Weight, length and head circumference Z
      scores were lower in the "term (-)" group compared to those in the "term (+)"
      group. CONCLUSIONS: The lean tissue deficits were maintained in the "term (-)"
      group while the differences in body fat percentage were not.

PMID- 29360049
TI  - Analysis of the elastic bending characteristics of cementless short hip stems
      considering the valgus alignment of the prosthetic stem.
AB  - BACKGROUND: The resultant hip force causes a varus torque which must be
      compensated by a shear force couple depending on the stem alignment of the
      prosthesis. Since the prosthesis is substantially less flexible than the bone,
      the interior of the femur is stiffened over the entire prosthesis length. The
      present study thus aims at analyzing short-stem prostheses for its elastic
      bending characteristics, considering inappropriate valgus alignment of the
      prosthetic stem. METHODS: Five short stem prostheses were implanted each in
      synthetic femora in a standardized manner - in neutral and valgus stem
      alignments. Bending movements were recorded applying a tilting torque MX of +/
      3.5 Nm in medio-lateral direction. Variance analyses and Friedman tests were
      used. A P-value <.05 was considered statistically significant. FINDINGS: Bending
      movements b1-b6 showed significant differences (P < .05). It could be shown that
      different stem alignments (P < .05) and different measuring points had a highly
      significant influence (P < .001) on the relative movements. Compared to the
      AIDA(r), the MiniHipTM as well as the Metha(r) stiffened the femur to a higher
      degree (P < .001). INTERPRETATION: Regarding the elastic bending behavior we see
      a relevant influence of the stems' design. We conclude that the short-stem
      principle does not necessarily require the shortest possible prosthesis but
      rather a long and thin extending stem tip to optimize the lever ratios, ensuring
      a more physiological bending behavior of the femur. In addition, without
      sufficient anchoring of the prosthesis, the valgus stem alignment could favor
      tilting of the implant and should therefore be avoided.

PMID- 29360050
TI  - Achievable accuracy of hip screw holding power estimation by insertion torque
      measurement.
AB  - BACKGROUND: To ensure stability of proximal femoral fractures, the hip screw must
      firmly engage into the femoral head. Some studies suggested that screw holding
      power into trabecular bone could be evaluated, intraoperatively, through
      measurement of screw insertion torque. However, those studies used synthetic
      bone, instead of trabecular bone, as host material or they did not evaluate
      accuracy of predictions. We determined prediction accuracy, also assessing the
      impact of screw design and host material. METHODS: We measured, under highly
      repeatable experimental conditions, disregarding clinical procedure complexities,
      insertion torque and pullout strength of four screw designs, both in 120
      synthetic and 80 trabecular bone specimens of variable density. For both host
      materials, we calculated the root-mean-square error and the mean-absolute
      percentage error of predictions based on the best fitting model of torque-pullout
      data, in both single-screw and merged dataset. FINDINGS: Predictions based on
      screw-specific regression models were the most accurate. Host material impacts on
      prediction accuracy: the replacement of synthetic with trabecular bone decreased
      both root-mean-square errors, from 0.54 / 0.76 kN to 0.21 / 0.40 kN, and mean
      absolute-percentage errors, from 14 / 21% to 10 / 12%. However, holding power
      predicted on low insertion torque remained inaccurate, with errors up to 40% for
      torques below 1 Nm. INTERPRETATION: In poor-quality trabecular bone, tissue
      inhomogeneities likely affect pullout strength and insertion torque to different
      extents, limiting the predictive power of the latter. This bias decreases when
      the screw engages good-quality bone. Under this condition, predictions become
      more accurate although this result must be confirmed by close in-vitro simulation
      of the clinical procedure.

PMID- 29360051
TI  - Assessing advanced theory of mind and alexithymia in patients suffering from
      enduring borderline personality disorder.
AB  - Findings on the theory of mind (ToM) abilities in borderline personality disorder
      (BPD) have been inconsistent. Surprisingly, no studies have focused on the
      complex aspects of ToM while simultaneously measuring alexithymia as well as
      comorbid depressive and anxiety symptoms, therefore, our study aimed to fill this
      gap. 30 female patients with BPD and 38 healthy controls (HCs) completed the Faux
      Pas Test (FPT) and the Toronto Alexithymia Scale-20 (TAS-20). The clinical and
      intellectual assessment comprised of the Structured Clinical Interview for DSM-IV
      TR Axis II Disorders (SCID-II), the Borderline Personality Inventory (BPI), the
      State-Trait Anxiety Inventory (STAI), the Center for Epidemiologic Studies
      Depression Scale-Revised (CESD-R), and the Raven's Progressive Matrices (RPM).
      Women with BPD scored significantly worse than HCs on overall ToM abilities.
      After controlling for the intelligence level, depressive symptoms, and state and
      trait anxiety, both groups presented a similar overall level of alexithymia. No
      correlation between the FPT and TAS-20 scores was found, suggesting that both
      constructs might be unrelated in BPD. Because ToM dysfunctions seem not to result
      from comorbid clinical symptoms, trait anxiety, or intellectual abilities, our
      study results suggest that ToM deficits might be considered a core feature of
      BPD.

PMID- 29360052
TI  - The impact of affective temperaments on clinical and functional outcome of
      Bipolar I patients that initiated or changed pharmacological treatment for mania.
AB  - BACKGROUND: Affective temperaments have been shown to impact on the clinical
      manifestations and the course of bipolar disorder. We investigated their
      influence on clinical features and functional outcome of manic episode. METHOD:
      In a naturalistic, multicenter, national study, a sample of 194 BD I patients
      that initated or changed pharmacological treatment for DSM-IV-TR manic episode
      underwent a comprehensive evaluation including briefTEMPS-M, CTQ, YMRS, MADRS,
      FAST, and CGI-BP. Factorial, correlation and comparative analyses were conducted
      on different temperamental subtypes. RESULTS: Depressive, cyclothymic, irritable
      and anxious temperaments resulted significantly correlated with each other. On
      the contrary, hyperthymic temperament scores were not correlated with the other
      temperamental dimensions. The factorial analysis of the briefTEMPS-M sub-scales
      total scores allowed the extraction of two factors: the Cyclothymic-Depressive
      Anxious (Cyclo-Dep-Anx) and the Hyperthymic. At final evaluation Dominant Cyclo
      Dep-Anx patients reported higer scores in MADRS and in CTQ emotional neglect and
      abuse subscale scores than Dominant Hyperthymic patients. The latter showed a
      greater functional outcome than Cyclo-Dep-Anx patients. CONCLUSIONS: Affective
      temperaments seem to influence the course of mania. Childhood emotional abuse and
      neglect were related to the cyclothymic disposition. Cyclothymic subjects showed
      more residual depressive symptoms and Hyperthymic temperament is associated with
      a better short-term functional outcome.

PMID- 29360053
TI  - Childhood trauma in schizophrenia spectrum disorders as compared to substance
      abuse disorders.
AB  - The prevalence of childhood trauma (CT) in schizophrenia spectrum disorders
      (SSDs) and substance abuse disorders (SUDs) is high. Direct comparisons of CT in
      these disorders are lacking, and it is not known whether there are differences in
      self-reported CT in SSDs as compared to SUDs. We aimed to compare the frequency,
      severity and types of CT in SDDs and SUDs. Patients with SSDs (n = 57) and SUDs
      (n = 57) were matched for age and gender. Overall levels of CT and CT subtypes
      were measured retrospectively by the Childhood Trauma Questionnaire Short-Form
      (CTQ-SF), and grouped into none/low and moderate/severe levels of CT. Group
      differences in CTQ-SF sum score and subscale scores, as well as differences in
      the severity of overall CT and CT subtypes were all non-significant. In both
      groups, 64.9% reported >= 1 subtypes of CT above cut-off. Of those who reported
      CT above the cut-off, 13.5% in the psychosis group reported >= 4 subtypes, as
      compared to 2.7% in the substance abuse group. We did not find statistically
      significant differences between SSDs and SUDs in terms of exposure to CT
      frequency or severity, all effect sizes were small (r < 0.15).

PMID- 29360054
TI  - Everyday memory problems in alcohol abuse and dependence: Frequency, patterns and
      patient-proxy agreement.
AB  - Using self-report to assess everyday memory in alcoholics presents challenges
      given the presence of both memory and metamemory deficits. Accordingly,
      evaluation of the reliability and validity of proxy ratings as well as the
      frequency of these memory lapses are of clinical importance. In the present
      study, 180 patient-proxy dyads completed the Prospective and Retrospective Memory
      Questionnaire (PRMQ). 31.7% of proxy-rated versus 2.8% of patient-rated
      prospective memory scores fell in the impaired to below average range. 15% of
      proxy-rated retrospective memory scores were below average, whereas none of the
      patients reported problems in this regard. Longer delays between intention
      formation and action yielded better prospective memory performance, while the
      opposite was true for retrospective memory. Agreement between patients and
      proxies was generally poor to fair across severity levels and the magnitude of
      observed differences was large (standardized response mean > 0.8). For all PRMQ
      items, exact agreement occurred in 45.3% of the cases. Larger patient-proxy
      discrepancy was associated with older age, less education and greater disease
      severity. Proxy ratings were internally consistent, significantly correlated with
      objective memory performance, and were sensitive to differences in overall PRMQ
      performance between severity groups. Caution should be used in the
      interpretations of patients' reports.

PMID- 29360055
TI  - Pressure dependence of X-rays produced by an LiTaO3 single crystal over a wide
      range of pressure.
AB  - The energy spectra of X-rays produced by an LiTaO3 single crystal have been
      measured at the pressures of 8 * 10-4-4Pa. The energy spectra showed that the
      endpoint energy steadily increased with decrease of pressure at 2-4Pa and
      gradually decreased with decrease of pressure at 0.1-2Pa, and became almost
      constant below 0.1Pa. The amount of X-rays steadily increased with decrease of
      pressure at 2-4Pa and almost saturated below 0.5Pa. The change of X-rays produced
      by the LiTaO3 single crystal was compared with the previous works and discussed
      in relation to the distance between the crystal surface and the target.

PMID- 29360056
TI  - Temperature dependence of 63Ni-Si betavoltaic microbattery.
AB  - This paper theoretically presented the temperature effects on the 63Ni-Si
      betavoltaic microbattery irradiated by a source with different thicknesses and
      activity densities at a temperature range 170-340K. Temperature dependences of
      the monolayer and interbedded 63Ni-Si betavoltaics at 213.15-333.15K were tested
      with respect to calculations. Results showed that the higher the thickness,
      activity density, and average energy of the source, the lower is the betavoltaic
      performance responds to temperature. With the increase in temperature, the Voc
      and Pmax of the upper, lower, and interbedded betavoltaics decreased linearly at
      low temperatures and decreased exponentially at high temperatures in the
      experiment. As predicted, the measured Voc and Pmax sensitivities of the lower
      betavoltaic with 4.90mCi/cm2 63Ni, -2.230mV/K and -1.132%, respectively, were
      lower than those with 1.96mCi/cm2 63Ni, -2.490mV/K and -1.348%, respectively.
      Compared with the calculated results, the prepared betavoltaics had lower Voc
      sensitivity and higher Pmax sensitivity. In addition, the measured Voc
      sensitivity of the interbedded betavoltaic in series is equal to the sum of those
      of the upper and lower ones as predicted. Moreover, the measured Pmax sensitivity
      of the interbedded betavoltaic is equal to the average of those of the two
      monolayers.

PMID- 29360057
TI  - Simulation and experimental measurement of radon activity using a multichannel
      silicon-based radiation detector.
AB  - In this study, high-precision radiation detector (HIPRAD), a new-generation
      semiconductor microstrip detector, was used for detecting radon (Rn-222)
      activity. The aim of this study was to detect radon (Rn-222) activity
      experimentally by measuring the energy of particles in this detector. Count-ADC
      channel, eta-charge, and dose-response values were experimentally obtained using
      HIPRAD. The radon simulation in the radiation detector was theoretically
      performed using the Geant4 software package. The obtained radioactive decay,
      energy generation, energy values, and efficiency values of the simulation were
      plotted using the root program. The new-generation radiation detector proved to
      have 95% reliability according to the obtained dose-response graphs. The
      experimental and simulation results were found to be compatible with each other
      and with the radon decays and literature studies.

PMID- 29360058
TI  - Rational design of aromatic surfactants for graphene/natural rubber latex
      nanocomposites with enhanced electrical conductivity.
AB  - HYPOTHESIS: Graphene nanoplatelets (GNPs) can be dispersed in natural rubber
      matrices using surfactants. The stability and properties of these composites can
      be optimized by the choice of surfactants employed as stabilizers. Surfactants
      can be designed and synthesized to have enhanced compatibility with GNPs as
      compared to commercially available common surfactants. Including aromatic groups
      in the hydrophobic chain termini improves graphene compatibility of surfactants,
      which is expected to increase with the number of aromatic moieties per surfactant
      molecule. Hence, it is of interest to study the relationship between molecular
      structure, dispersion stability and electrical conductivity enhancement for
      single-, double-, and triple-chain anionic graphene-compatible surfactants.
      EXPERIMENTS: Graphene-philic surfactants, bearing two and three chains phenylated
      at their chain termini, were synthesized and characterized by proton nuclear
      magnetic resonance (1H NMR) spectroscopy. These were used to formulate and
      stabilize dispersion of GNPs in natural rubber latex matrices, and the properties
      of systems comprising the new phenyl-surfactants were compared with commercially
      available surfactants, sodium dodecylsulfate (SDS) and sodium
      dodecylbenzenesulfonate (SDBS). Raman spectroscopy, field emission scanning
      electron microscopy (FESEM), atomic force microscopy (AFM), and high-resolution
      transmission electron microscopy (HRTEM) were used to study structural properties
      of the materials. Electrical conductivity measurements and Zeta potential
      measurements were used to assess the relationships between surfactant
      architecture and nanocomposite properties. Small-angle neutron scattering (SANS)
      was used to study self-assembly structure of surfactants. FINDINGS: Of these
      different surfactants, the tri-chain aromatic surfactant TC3Ph3 (sodium 1,5-dioxo
      1,5-bis(3-phenylpropoxy)-3-((3phenylpropoxy)carbonyl) pentane-2-sulfonate) was
      shown to be highly graphene-compatible (nanocomposite electrical conductivity =
      2.22 * 10-5 S cm-1), demonstrating enhanced electrical conductivity over nine
      orders of magnitude higher than neat natural rubber-latex matrix (1.51 * 10-14 S
      cm-1). Varying the number of aromatic moieties in the surfactants appears to
      cause significant differences to the final properties of the nanocomposites.

PMID- 29360059
TI  - Impact of viscous droplets on different wettable surfaces: Impact phenomena, the
      maximum spreading factor, spreading time and post-impact oscillation.
AB  - In this paper, we experimentally investigated the impact dynamics of different
      viscous droplets on solid surfaces with diverse wettabilities. We show that the
      outcome of an impinging droplet is dependent on the physical property of the
      droplet and the wettability of the surface. Whereas only deposition was observed
      on lyophilic surfaces, more impact phenomena were identified on lyophobic and
      superlyophobic surfaces. It was found that none of the existing theoretical
      models can well describe the maximum spreading factor, revealing the complexity
      of the droplet impact dynamics and suggesting that more factors need to be
      considered in the theory. By using the modified capillary-inertial time, which
      considers the effects of liquid viscosity and surface wettability on droplet
      spreading, a universal scaling law describing the spreading time was obtained.
      Finally, we analyzed the post-impact droplet oscillation with the theory for
      damped harmonic oscillators and interpreted the effects of liquid viscosity and
      surface wettability on the oscillation by simple scaling analyses.

PMID- 29360060
TI  - Epistemic companions: shared reality development in close relationships.
AB  - We propose a framework outlining the development of shared reality in close
      relationships. In this framework, we attempt to integrate disparate close
      relationship phenomena under the conceptual umbrella of shared reality. We argue
      that jointly satisfying epistemic needs-making sense of the world together-plays
      an important but under-appreciated role in establishing and maintaining close
      relationships. Specifically, we propose that dyads progress through four
      cumulative phases in which new forms of shared reality emerge. Relationships are
      often initiated when people discover Shared Feelings, which then facilitate the
      co-construction of dyad-specific Shared Practices. Partners then form an
      interdependent web of Shared Coordination and ultimately develop a Shared
      Identity. Each emergent form of shared reality continues to evolve throughout
      subsequent phases, and, if neglected, can engender relationship dissolution.

PMID- 29360061
TI  - Pulse steroid therapy in multiple sclerosis and mood changes: An exploratory
      prospective study.
AB  - BACKGROUND: Several reports suggest a higher risk of psychiatric disorders after
      high-dose corticosteroids (HDC), routinely used to treat clinical relapses in
      multiple sclerosis (MS). The present study aimed to examine the possible effect
      of HDC on mood in patients with MS and to determine the specific factors that
      influence mood changes. METHODS: The study included MS patients prior to receive
      HDC. The presence of depressive and bipolar symptoms was determined with the Beck
      Depression Inventory-Second Edition (BDI-II) and the Mood Disorder Questionnaire
      (MDQ). These assessments were made at three time points: prior to HDC initiation,
      after HDC completion, and 1 month after HDC. RESULTS: The study included 101 MS
      patients. At baseline, 32 (31.7%) patients had depressive symptoms (BDI-II scores
      >= 14) and 20 (19.8%) patients had bipolar symptoms (MDQ scores >= 7). While it
      was observed a reduction of BDI-II scores after HDC, an increase in MDQ score was
      found in patients with MDQ positivity at baseline, resulting associated with a
      higher number of HDC infusions (p 0.018). CONCLUSIONS: Our results emphasize the
      importance of accurate screening for mood disorders in patients with MS prior to
      HDC initiation, and indicate that HDC should be used with caution in patients
      with MDQ positivity.

PMID- 29360062
TI  - Intracardiac shunts following transcatheter aortic valve implantation: a
      multicentre study.
AB  - AIMS: The aim of this study was to describe the incidence, mechanisms, management
      and outcomes of intracardiac shunts (ICS) following TAVI. METHODS AND RESULTS:
      This was a multicentre registry across 10 centres aimed at gathering all cases of
      ICS (1.1%) including infection-related (IRICS, 0.3%) or aseptic (AICS, 0.8%)
      shunts. Patients presented porcelain aorta (24% vs. 6.8%, p=0.024) and had been
      treated with predilation (88% vs. 68.5%, p=0.037) or post-dilation (59.1% vs.
      19.3%, p<0.001) more often. Median time from intervention to diagnosis of ICS was
      10 days (IQR: 2-108), being longer for IRICS (171 [63-249] vs. 3 [1-12] days,
      p=0.002). Interventricular septum (55.6%) and anterior mitral leaflet (57.2%)
      were the most common locations for AICS and IRICS, respectively. Most patients
      (76%) developed heart failure but 64% were medically managed. Seven patients
      (38.9%) underwent percutaneous closure of AICS. The in-hospital mortality rate
      was 44% (IRICS 100%, AICS 27.8%) compared to global TAVI recipients (8.1%,
      p<0.001). At one-year follow-up, 76% of the patients had died. ICS, logistic
      EuroSCORE, and moderate-severe residual aortic regurgitation were independent
      predictors of death. CONCLUSIONS: Post-TAVI ICS are an uncommon complication
      independently associated with high early mortality. Currently, most therapeutic
      alternatives yield poor results but percutaneous closure of AICS was feasible and
      is a promising alternative.

PMID- 29360063
TI  - Optimising mitral repair in functional regurgitation: transcatheter annuloplasty
      can counteract left ventricle-mitral ring mismatch.

PMID- 29360064
TI  - Overview and proposed terminology for the reverse controlled antegrade and
      retrograde tracking (reverse CART) techniques.
AB  - During recent years, equipment and techniques for percutaneous coronary
      intervention (PCI) of chronic total occlusions (CTO) have improved significantly.
      The retrograde approach remains critical to the improved success of CTO PCI.
      Currently, the reverse controlled antegrade and retrograde tracking (CART)
      technique has become the dominant retrograde wire crossing technique. In this
      article, we propose a standardised terminology and classification for this
      technique divided into three subtypes: a) conventional reverse CART, usually
      involving the use of large balloons on the antegrade wire to achieve re-entry
      within the CTO segment; b) "directed" reverse CART, which is characterised by
      small antegrade balloon size and more active, intentional vessel tracking and
      penetration with a controllable retrograde wire, still within the CTO segment;
      and c) "extended" reverse CART, in which the intimal/subintimal dissection is
      extended proximal or distal to the CTO segment, achieving re-entry outside the
      CTO segment. The proposed standardised terminology will facilitate the
      communication, teaching and adoption of the reverse CART techniques.

PMID- 29360065
TI  - Balloon pulmonary angioplasty relieves haemodynamic stress towards untreated-side
      pulmonary vasculature and improves its resistance in patients with chronic
      thromboembolic pulmonary hypertension.
AB  - AIMS: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by
      organised thrombotic obliteration of major vessels and small-vessel arteriopathy
      in the non-thrombosed vessels. The aim of this study was to investigate the
      impact of balloon pulmonary angioplasty (BPA) on the non-BPA-side pulmonary
      vasculature in patients with CTEPH. METHODS AND RESULTS: This study explored the
      outcomes of 20 unilateral BPA sessions in 13 CTEPH patients. We measured the
      pulmonary vascular resistance (PVR), pulmonary artery (PA) flow in the BPA-side
      and non-BPA-side lungs, respectively, using phase contrast MRI and cardiac
      catheterisation. The interval from BPA to the follow-up evaluation was 92.8+/
      52.0 days. A single session of BPA decreased mean PA pressure from 37.4+/-6.2 to
      30.9+/-6.5 mmHg (p<0.001). In the BPA side, BPA increased the PA flow from 1.58+/
      0.65 to 1.95+/-0.62 L/min (p=0.001) and decreased the PVR from 27.3+/-27.4 to
      14.4+/-9.0 Wood units (p=0.004). In contrast, it decreased both the non-BPA-side
      PA flow from 2.25+/-0.64 to 1.90+/-0.23 L/min (p=0.008) and the non-BPA-side PVR
      from 14.8+/-6.6 to 12.8+/-3.9 Wood units (p=0.01). CONCLUSIONS: BPA could relieve
      haemodynamic stress towards the non-BPA-side vasculature and decrease its PVR in
      patients with CTEPH, suggesting that it can suppress or regress the progression
      of the small-vessel arteriopathy in non-BPA-side vasculature, presumably due to
      haemodynamic unloading.

PMID- 29360066
TI  - PERKAT RV: first in vivo data of a novel right heart assist device.
AB  - AIMS: Mechanical right ventricular (RV) support offers a treatment option for
      critically ill patients with RV failure (RVF). We developed an assist device for
      rapid percutaneous implantation. The aim of the present study was to investigate
      the implantation procedure, haemodynamic performance and possible side effects of
      the novel right ventricular assist device - PERKAT RV - in an animal model.
      METHODS AND RESULTS: The PERkutane KATheterpumptechnologie RV (PERKAT RV) device
      consists of a nitinol chamber covered by foil containing inflow valves. An outlet
      tube is attached to its distal part. The system is designed for 18 Fr
      percutaneous implantation. The chamber is unfolded in the inferior vena cava
      while the outlet tube bypasses the right heart with the tip in the pulmonary
      trunk. An IABP balloon is placed inside. Balloon deflation generates blood flow
      into the chamber; during inflation, blood is guided into the pulmonary arteries.
      Acute RVF was induced by venous injection of Sephadex in seven sheep for
      evaluation of the device. The PERKAT RV was able to improve haemodynamics
      immediately generating a median increase in cardiac output of 59%. Longer pump
      support was evaluated in a second study. Four sheep were supported for eight
      hours without any problems. CONCLUSIONS: The percutaneous implantation and
      explantation of the PERKAT RV device was possible in the designed way. The sheep
      studies proved beneficial haemodynamic effects in acute RVF. The system offers
      easy and safe treatment in acute RVF.

PMID- 29360067
TI  - One-year rehospitalisation after percutaneous coronary intervention: a
      retrospective analysis.
AB  - AIMS: The aim of the study was to evaluate the incidence and causes of
      rehospitalisation within one year after percutaneous coronary intervention (PCI)
      in a country where the National Health Service provides universal tax-supported
      healthcare, guaranteeing residents free hospital access. METHODS AND RESULTS:
      Between January 2010 and September 2014, 17,111 patients were treated with PCI in
      two University Hospitals in Western Denmark. Patients who were readmitted within
      one year after PCI were identified. The overall one-year readmission rate was
      50.4%. The cause was angina/myocardial infarction (MI) in 4,282 patients (49.7%),
      and other reasons in 4,334 (50.3%). Predictors of angina/MI-related readmissions
      were female gender (odds ratio [OR] 1.15, 95% confidence interval [CI]: 1.07
      1.25), diabetes (OR 1.14, 95% CI: 1.04-1.26), age (per 10-year increase) (OR
      0.86, 95% CI: 0.83-0.88), and indication for index PCI (stable angina pectoris as
      reference): ST-segment elevation myocardial infarction (OR 1.34, 95% CI: 1.23
      1.47) and non-ST-segment elevation myocardial infarction (OR 1.18, 95% CI: 1.08
      1.29). Predictors for other readmissions were female gender (OR 1.09, 95% CI:
      1.01-1.18), diabetes (OR 1.29, 95% CI: 1.18-1.42), age (OR 1.30, 95% CI: 1.26
      1.34) and Charlson comorbidity index >=3 (OR 3.03, 95% CI: 2.71-3.27).
      CONCLUSIONS: In an unselected patient cohort treated with PCI, half of the
      patients were rehospitalised within one year, highlighting the impact of
      comorbidity in patients with ischaemic heart disease.

PMID- 29360068
TI  - [Variation analysis of the number of copies and methylene patterns in region
      15q11-q13].
AB  - Human chromosome 15q11-q13 region is prone to suffer genetic alterations. Some
      genes of this region have a differential monoallelic imprinting-regulated
      expression pattern. Defects in imprinting regulation (IE), uniparental disomy
      (UPD) or copy number variation (CNV) due to chromosomal breakpoints (BP) in 15q11
      q13 region, are associated with several diseases. The most frequent are Prader
      Willi syndrome, Angelman syndrome and 15q11-q13 microduplication syndrome. In
      this work, we analyzed DNA samples from 181 patients with phenotypes which were
      compatible with the above-mentioned diseases, using Methyl specific-multiplex
      ligation-dependent probe amplification (MS-MLPA). We show that, of the 181
      samples, 39 presented alterations detectable by MS-MLPA. Of those alterations,
      61.5% (24/39) were deletions, 5.1% (2/39) duplications and 33.3% (13/39) UPD/IE.
      The CNV cases were 4 times more frequent than UPD/IE (OR= 4; IC 95%: 1.56-10.25),
      consistent with the literature. Among the CNVs, two atypical cases allow to
      postulate new possible BP sites that have not been reported previously in the
      literature.

PMID- 29360069
TI  - [Calcium response to vitamin D supplementation].
AB  - Several studies show the importance of serum vitamin D sufficient levels to
      prevent multiple chronic diseases. However, vitamin D supplementation and its
      effects on urine calcium excretion remain controversial. The objective of this
      prospective and interventional study was to evaluate urine calcium excretion in
      women with normal calciuria or hypercalciuria, once serum vitamin D sufficiency
      was achieved. We studied 63 women with idiopathic hypercalciuria, (9 with renal
      lithiasis) and 50 normocalciuric women. Both groups had serum vitamin D levels
      low (deficiency or insufficiency). Baseline urine calcium excretion was measured
      before being supplemented with vitamin D2 or D3 weekly or vitamin D3 100.000 IU
      monthly. Once serum vitamin D levels were corrected achieving at least 30 ng/ml,
      a second urine calcium excretion was obtained. Although in the whole sample we
      did not observe significant changes in urine calcium excretion according to the
      way of supplementation, some of those with weekly supplementation had significant
      higher urine calcium excretion, 19% (n = 12) of hypercalciuric women and 12% (n =
      6) of the normocalciuric group. Monthly doses, also showed higher urine calcium
      excretion in 40% of hypercalciuric women (n = 4/10) and in 44% (n = 4/9) of the
      renal lithiasis hypercalciuric patients. In conclusion, different ways of vitamin
      D supplementation and adequate serum levels are safe in most patients, although
      it should be taken into account a subgroup, mainly with monthly loading doses,
      that could increase the calciuria significantly eventually rising renal lithiasis
      risk or bone mass loss, if genetically predisposed.

PMID- 29360070
TI  - [Reduction of inappropriate prescriptions and adverse effects to medications in
      hospitalized elderly patients].
AB  - Together, potentially inappropriate prescribing of medications (PIP) and
      appropriate prescribing omission (APO) constitute a problem that requires
      multiple interventions to reduce its size and the occurrence of adverse drug
      events (ADE). This study aims to assess PIP, APO, ADE before and after the
      intervention of a clinical pharmacist over medical prescriptions for elderly
      hospitalized patients. In a before-after study, a total of 16 542 prescriptions
      for 1262 patients were analyzed applying the criteria defined in both STOPP-
      START (screening tool of older people's prescriptions and screening tool to alert
      to right treatment). The intervention consisted in lectures and publications on
      STOPP-START criteria made available to all the areas of the hospital and
      suggestions made by the clinical pharmacist to the physician on each individual
      prescription. Before intervention, PIM was 48.9% on admission and 46.1% at
      discharge, while after the intervention it was 47.4% on admission and 16.7% at
      discharge. APO was 10% on admission and 7.6% at discharge, while after
      intervention it was 12.2% on admission and 7.9% at discharge. ADE were 50.9%
      before and 34.4% after intervention. The frequency of return to emergency was
      12.2% and 4.7% before and after intervention. PIM, EAM, conciliation error,
      clinically serious drug interaction, and delirium were reduced to statistically
      significant levels. In line with various international studies, the intervention
      showed to attain positive results.

PMID- 29360071
TI  - [Scientific production from public hospitals of the City of Buenos Aires, 2017].
AB  - The number of publications in the scientific literature coming from an
      institution is an indicator of its scientific production. The scientific
      production of the hospitals of the Government of the City of Buenos Aires (GCBA)
      has been evaluated previously, but without discriminating how much of that
      production corresponded to other academic institutions settled there (University
      of Buenos Aires, UBA, National Council of Scientific Research and Techniques,
      CONICET). Our objective was to evaluate the publications included in PubMed that
      correspond to hospitals of the GCBA, describe their main characteristics, and
      discriminate the contribution of other academic institutions (UBA and CONICET).
      It is a cross-sectional study based on a PubMed search, using the name of each of
      the 34 GCBA hospitals, CONICET and UBA in the "affiliation" field. In total, 2727
      publications from GCBA hospitals were identified (4.6% of Argentine
      publications); 73.9% in English, 78.9% in relation to humans, 37.2% in the last 5
      years; 6.4% with high level of evidence (clinical trials and meta-analysis), and
      28.4% including children. Compared to the national total, the GCBA publications
      include fewer works in English, more research in humans, more clinical trials and
      more research in children. Of the publications corresponding to hospitals of the
      GCBA, 90.4% did not share the affiliation with CONICET or with UBA. In
      conclusion, the GCBA hospitals generated 4.6% of the total Argentine publications
      in PubMed; and 90% of these was not shared with UBA or CONICET. Publications from
      GCBA institutions include more clinical trials and research in children.

PMID- 29360072
TI  - [Dengue, zika, chikungunya and the development of vaccines].
AB  - Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted
      by Aedes mosquitoes, have spread in recent decades in humid tropical and
      subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV
      infection confers lasting immunity against the infecting serotype but increases
      the risk of serious disease upon reinfection by any of the other three. The
      recombinant tetravalent vaccine Dengvaxia(r) prevents severe dengue and
      hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in
      Argentina, for ages 9 to 45, but is not included in the national vaccination
      calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID
      / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with
      microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is
      still not effective treatment nor vaccine with proven activity against ZIKV.
      There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of
      CHIKV fever have a complication: the development of chronic post-disease
      rheumatism. There are not approved vaccines for humans nor effective antiviral
      therapies. The seriousness of these virosis has contributed to a rapid progress
      in the knowledge of the infection processes and the immune response. For now,
      Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the
      vaccine will be the most effective means of controlling these viruses. Here we
      summarize information about these arbovirosis in Argentina and Brazil and
      describe advances in the development and evaluation of vaccines.

PMID- 29360073
TI  - Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy.
      Trends and perspectives.
AB  - Hepatocellular carcinoma (HCC) is the second cause of cancer-related death in the
      world and is the main cause of death in cirrhotic patients. Unfortunately, the
      incidence of HCC has grown significantly in the last decade. Curative treatments
      such as surgery, liver transplantation or percutaneous ablation can only be
      applied in less than 30% of cases. The multikinase inhibitor sorafenib is the
      first line therapy for advanced HCC. Regorafenib is the standard of care for
      second-line patients. However, novel and more specific potent therapeutic
      approaches for advanced HCC are still needed. The liver constitutes a unique
      immunological microenvironment, although anti-tumor immunity seems to be feasible
      with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further
      increased by combining checkpoint inhibitors or by applying loco-regional
      treatments. The success of immune checkpoint blockade has renewed interest in
      immunotherapy in HCC.

PMID- 29360074
TI  - [Pituitary spindle cell oncocytoma].
AB  - Spindle cell oncocytoma is an infrequent benign non-endocrine sellar neoplasm.
      Due to its similar morphology to pituitary adenomas, consideration of this
      differential diagnosis would conduce to a more careful surgical approach in order
      to avoid intraoperative bleeding and aiming to a complete resection, on which
      depends long-term outcomes. We present the case of a 60-year-old male who
      complained about visual abnormalities, with computerized visual field
      confirmation. On biochemistry, a panhypopituitarism was detected. The brain
      magnetic resonance images showed a sellar mass. A non-functioning pituitary
      macroadenoma was presumptively diagnosed and due to the visual impairment,
      surgical transesphenoidal treatment was indicated. The histological diagnosis was
      spindle cell oncocytoma. Five months after surgery, the control image
      demonstrated a lesion that was considered as remnant tumor, hence radiosurgery
      was performed. During the follow-up, the tumor reduced its size and four years
      after initial treatment, the sellar resonance imaging showed disappearance of the
      residual tumor. Communication of new cases of this rare entity will enlarge the
      existing evidence and will help to determinate the most effective treatment and
      prognosis.

PMID- 29360075
TI  - [Hemophagocytosis secondary to dengue fever].
AB  - Dengue virus infection constitutes a major public health problem worldwide. It is
      caused by a virus belonging to the Flaviviridae family. It produces a wide range
      of clinical presentations, from asymptomatic infection to severe forms of the
      disease with hemorrhagic fever or shock secondary to capillary leak syndrome.
      Four serotypes have been described; serotype 2 and serotype 3 are associated with
      the most severe forms of the disease. The diagnosis is based on laboratory tests
      aimed to detect antibodies, viral RNA, or antigens in serum. The hemophagocytic
      syndrome is generated by a dysfunction of the immune system with clinical,
      hematological, biochemical and histological manifestations. The association
      between these two entities is described as an unusual and severe presentation of
      dengue fever. We present a case of an adult patient with this association and
      very high blood levels of ferritin, who responded favorably to supportive care.

PMID- 29360076
TI  - [Isolated intestinal angioedema induced by enalapril].
AB  - Angioedema induced by angiotensin converting enzyme inhibitors is a rare entity
      characterized by skin and mucosal edema, due to increased vascular permeability
      caused by inhibition of the converting enzyme and subsequent increase in
      bradykinin. It frequently presents with facial and mucosal involvement, being
      uncommon the intestinal or airway compromise. Intestinal angioedema may be
      associated with facial or isolated angioedema, the latter being exceptional. It
      is associated with recurrent episodes of pain, abdominal distention and watery
      diarrhea which complete recovery in two or three days. Although it is a rare
      entity, the fact that it is associated with frequently used drugs makes us
      include it in the differential diagnosis of recurrent abdominal pain. We report a
      case of isolated intestinal angioedema associated with the use of enalapril.

PMID- 29360077
TI  - [Struma ovarii associated with Graves' disease].
AB  - Hyperthyroidism is defined as an excessive production of thyroid hormones by
      eutopic or ectopic mature thyroid tissue. The overall prevalence of
      hyperthyroidism is 1.2% and the most common cause is Graves' disease. Struma
      ovarii represents 1% of all ovarian tumors and is an uncommon cause of ectopic
      hyperthyroidism. It is benign in >90% of the cases; usually asymptomatic, and
      only 8% are presented with thyrotoxicosis, being rare its association with
      Graves' disease. We report the case of a patient with this association.

PMID- 29360078
TI  - [Solitary fibrous tumor and Doege-Potter syndrome].
AB  - The solitary fibrous tumor is uncommon. Even though it frequently locates in the
      pleura, a few cases have been reported in the retroperitoneum. Differentiation
      from other neoplasms is difficult, and therefore the diagnosis is always attained
      through histological examination. Although solitary fibrous tumors have variable
      clinical behaviors, a better comprehension of the location and its imaging
      characteristics would help to decrease the list of differential diagnoses. We
      report a solitary fibrous tumor located in the retroperitoneum whose diagnosis
      was confirmed by histological examination.

PMID- 29360079
TI  - [4pp Mucocutaneous manifestations of methotrexate toxicity].
AB  - Methotrexate is an antimetabolite analog to folic acid that competitively
      inhibits the enzyme dihydrofolate reductase and thymidylate synthetase, essential
      for the synthesis of DNA and RNA. It is widely used in dermatology and its
      adverse effects on the skin and mucous membranes are varied, including mild and
      severe reactions. The appearance of erosions and skin ulcers as a manifestation
      of methotrexate cytotoxicity are quite infrequent. These would represent an early
      cutaneous sign of pancytopenia due to marrow toxicity secondary to this drug. In
      most of the cases there are cutaneous diseases prior to ulceration, mainly
      psoriasis. In the absence of underlying dermatitis, the presence of ulcerations
      is very rare. We present eight cases of patients with cutaneous signs of
      methotrexate poisoning, with and without previous dermatoses. Most of them
      associated mucositis and bone marrow involvement. Treatment guidelines are
      recommended.

PMID- 29360081
TI  - [A century away from the University Reform and beyond football: Does science have
      social value?]

PMID- 29360080
TI  - [Hooke and Company. Science and literature].

PMID- 29360082
TI  - [Diabetes by immunotherapy].

PMID- 29360083
TI  - [New insulin analogs. Its use in patients with chronic kidney disease].

PMID- 29360084
TI  - [Antibiotics and omeprazole].

PMID- 29360085
TI  - Editorial.

PMID- 29360086
TI  - Surgical Results and Complications of Cochlear Implantation in Far-Advanced
      Otosclerosis.
AB  - OBJECTIVE: To report surgical results and complications of cochlear implantation
      in patients with far-advanced otosclerosis (FAO). MATERIALS AND METHODS: This was
      a retrospective chart review of surgical results in terms of electrode insertion
      as well as peri- and postoperative complications. Ten cochlear implantations
      (CIs) were performed in eight patients with FAO. A prior stapedotomy had been
      performed in all cases. RESULTS: Full electrode insertion was achieved in nine of
      the 10 operations (90%) and partial insertion in one operation. An unintended
      opening of the vestibule during drilling was the only perioperative complication.
      Postoperative complications occurred as two cases of vertigo (one prolonged). No
      chorda tympani syndrome and no cases of facial nerve stimulation were noted.
      CONCLUSION: Although based on a limited number of cases, we conclude that full
      electrode insertion can be achieved in almost all cases and that major
      complications are infrequent in CI in patients with FAO. Postoperative vertigo
      appears to be the most commonly occurring complication.

PMID- 29360087
TI  - Changes in Proinflammatory Cytokines in the Cochlea in Relation to Hearing
      Thresholds in Noise-Exposed Rats.
AB  - OBJECTIVE: Our aim was to investigate time effects in proinflammatory cytokines
      and the auditory brainstem response (ABR) thresholds of rat cochlea exposed to
      noise. MATERIALS AND METHODS: Twenty-one rats were divided into two groups: the
      control group and the noise group. As high as 115 dB sound pressure of white
      noise was administered to the noise group of 16 rats for 3 h a day for 10 days.
      This group was further split into four subgroups based on the timing of
      sacrifice: 3rd hour group, 12th hour group, 24th hour group, and 28th day group.
      ABR thresholds were measured in all the rats, after the noise exposure and right
      before being sacrificed. Proinflammatory cytokine levels (IL-6, IL-1beta, and TNF
      alpha) at the cochlea were measured. RESULTS: We found a significant difference
      between the first ABR thresholds (5 dB nHL) and the post-exposure ABR thresholds
      in each group (25 dBnHL, 35 dBnHL, 15 dBnHL, and 17.50 dBnHL for the 3rd hour
      group, 12th hour group, 24th hour group, and 28th day group, respectively). The
      IL-1beta levels in the 3rd hour group and 12th hour group were significantly
      higher than those in the control group and other noise subgroups. The TNF-alpha
      level in the 3rd hour group was significantly higher than that in the control
      group and other noise subgroups. CONCLUSION: It seems reasonable to point out a
      direct correlation between the cytokine levels and hearing threshold levels after
      the noise exposure. This correlation was the highest for IL-1beta. This result
      suggested a significant role of proinflammatory cytokines in hearing
      deterioration after noise exposure.

PMID- 29360088
TI  - The Adenoid Microbiome in Recurrent Acute Otitis Media and Obstructive Sleep
      Apnea.
AB  - OBJECTIVE: To compare the microbial flora of adenoids from patients with
      recurrent acute otitis media (AOM) and patients with obstructive sleep apnea
      (OSA). MATERIALS AND METHODS: This study was prospective and controlled. Adenoids
      were obtained from children undergoing adenoidectomy for recurrent AOM (n=7) or
      OSA (n=13). Specimens were processed for total deoxyribonucleic acid (DNA)
      isolation. 16s DNA 454-pyrosequencing was performed on AOM (n=5) and OSA (n=5)
      specimens. All specimens were analyzed by real-time polymerase chain reaction for
      the quantification of the oral commensal bacteria, Streptococcus salivarius.
      RESULTS: All adenoid specimens had evidence of microbes. Haemophilus influenzae,
      Moraxella catarrhalis, Streptococcus pneumoniae, Pseudomonas aeruginosa, and
      Staphylococcus aureus were among the dominant species in all samples. S.
      salivarius, Prevotella sp. and Terrahaemophilus aromaticivorans were more common
      on adenoids from OSA patients (p<0.05). Bradyrhizobium sp. was more common on
      adenoids from patients with recurrent AOM (p<0.05). The microbial profiles
      associated with recurrent AOM were different from, but overlapped with OSA. S.
      salivarius quantified by real-time PCR was not different between the two groups.
      CONCLUSION: Microbes are present on all adenoid specimens, though the microbial
      profile differs between recurrent AOM and OSA. The clinical significance of these
      differences remains to be determined.

PMID- 29360089
TI  - BPIFA1 Gene Expression in the Human Middle Ear Mucosa.
AB  - OBJECTIVE: The bactericidal/permeability-increasing, fold-containing family
      member A1 (BPIFA1) gene codes a secretory protein (BPIFA1), which is present in
      the respiratory tract mucosa, and is part of the innate immune system. This study
      aimed to prove that BPIFA1 gene expression exists in the human middle ear mucosa.
      MATERIALS AND METHODS: In total, 32 patients participated in the study between
      March 2016 and September 2016. Seventeen patients had chronic otitis media with
      cholesteatoma (COMC) and 15 had bilateral sensorineural hearing loss (BSHL). The
      patients with COMC underwent radical mastoidectomy with cholesteatoma removal and
      those with BSHL underwent cochlear implantation. Part of the processus mastoideus
      mucosa was examined for BPIFA1 gene expression and the two groups were compared.
      RESULTS: For the first time, BPIFA1 gene expression was examined in the mucosa of
      the human middle ear, and it was verified in 100% (n=32) of the participants. We
      confirmed that there is a difference in the BPIFA1 expression in 83.33% of the
      patients with COMC compared to the patients with BSHL but this difference was not
      statistically significant (p=0.947; probably due to the low number of
      participants in this group). CONCLUSION: It is highly likely that the BPIFA1
      protein participates in the non-specific immune defense of the middle ear and is
      relevant to the pathogenesis of the inflammatory diseases of the middle ear.

PMID- 29360090
TI  - Clinical and Audiologic Characteristics of Tinnitus in Subjects Aged <65 and >65
      Years.
AB  - OBJECTIVE: This study compared the characteristics of tinnitus, by audiologic
      tests and questionnaires, in older and younger subjects. MATERIALS AND METHODS:
      Medical records of 258 outpatients with tinnitus were retrospectively reviewed.
      Characteristics compared in subjects aged <65 and >65 years included patient
      history and the results of physical examinations, questionnaires, and audiologic
      tests. RESULTS: Fifty-nine patients were aged 65 years and older (older group),
      and 199 were less than 65 years old (younger group). The prevalence of chronic
      tinnitus was significantly higher in the older group (p<0.05). Assessments of
      audiologic configuration showed that the rate of high frequency steeply sloping
      configuration was significantly higher (p<0.05). The rate of sensorineural
      hearing loss was significantly higher in the older group (p<0.05). On
      tinnitograms, loudness was significantly higher in the older group (p<0.05).
      Auditory brainstem responses analysis showed that V latency was longer in the
      older group (p<0.05). The older group showed lower responses at every frequency
      on distortion product otoacoustic emissions (p<0.05) and lower signal-to-noise
      ratio at every frequency on transient evoked otoacoustic emissions (p<0.05).
      CONCLUSION: The clinical manifestations of tinnitus and audiological results
      differ between older and younger subjects with tinnitus.

PMID- 29360091
TI  - Ear Fullness as a Symptom of Endolymphatic Hydrops in non-Meniere's Patient.
AB  - OBJECTIVE: 1) To determine if unexplained ear fullness might be a symptom of
      endolymphatic hydrops (EH) by using Electrocochleography (ECochG) SP/AP area and
      amplitude ratios. 2) To assess if individuals with unexplained ear fullness
      without vertigo differ significantly from individuals with ear fullness due to
      Meniere's disease (MD). MATERIALS AND METHODS: In a case-control study in our
      tertiary care center, we evaluated 62 ears across 49 patients, including 18
      normal healthy ears across 12 control patients, 26 ears with unexplained ear
      fullness across 20 patients (6 had bilateral symptoms of ear fullness), and 18
      ears with definite MD across 17 patients (1 bilateral disease). Outcome measures
      were SP/AP amplitude and area ratio, hearing threshold, and air-bone gap.
      RESULTS: The analysis of auditory thresholds revealed a significant group effect
      for air conduction [F(2,50)=49.627; p<0.001] and for bone conduction
      [F(2,50)=45.625; p<0.001]. We observed significant differences between MD
      (36.36+/-4.87) and control patients (19.85+/-2.55) (p=0.015) for amplitude ratio.
      Moreover, significant differences were noted between MD (5.32+/-1.06) and
      controls (1.36+/-0.07) (p=0.035) and between ear fullness (5.16+/-1.17) and
      controls (p=0.026) for the area ratio parameter. No significant correlation was
      observed between SP/AP area or amplitude ratios and air-bone gap at any of the
      tested frequencies. The amplitude ratio was not significantly different between
      the ear fullness and control groups (p=0.406). The area and amplitude ratios did
      not reveal significant differences between MD and ear fullness (p=1.00).
      CONCLUSION: EH can be present even in the absence of vertigo and when patients
      report unexplained ear fullness. This study, to our knowledge, is the first to
      possibly allow early identification of cochlear EH in patients suffering from ear
      fullness without vertigo.

PMID- 29360092
TI  - Management of Necrotizing Otitis Externa: Our Experience with Forty-Three
      Patients.
AB  - OBJECTIVE: To assess the impact of the introduction of a dedicated management
      protocol of necrotizing otitis externa patients with joint care between
      otorhinolaryngology and infectious diseases. MATERIALS AND METHODS: Retrospective
      review of case notes and the otorhinolaryngology department database of all
      adults admitted with necrotizing otitis externa at our teaching hospital over a 5
      year period. The patients were split into two groups (first group of 10 patients
      prior to the introduction of the dedicated management protocol, and a second
      group of 33 patients managed after the introduction of this protocol). RESULTS:
      Of the 43 patients included in the study, diabetes mellitus was present in 83.7%.
      Pseudomonas aeruginosa was grown in 67.4% of patients. All 43 patients underwent
      computed tomography and magnetic resonance imaging (with contrast) scans.
      Surgical intervention was undertaken in 25.6% of patients. Mean follow-up was 10
      months (SD, +/-7 months). Of the 43 patients, 79.1% made a full recovery and were
      discharged. Relapse occurred in 9.3% of patients. One patient died because of a
      myocardial infarction 4 months after treatment. The mean length of stay was
      significantly lower after the protocol was introduced (25.6+/-5.3 vs. 14.2+/-3.8
      days, p=0.001), and the duration of treatment was also significantly lower after
      the protocol (21.2+/-6.8 vs. 14.3+/-4.3 weeks, p=0.01). CONCLUSION: The
      introduction of a dedicated management protocol and joint care with
      otorhinolaryngology and infectious diseases resulted in improved care and
      decreased length of stay in patients. Early diagnosis and involvement with the
      relevant teams as well as prompt intervention are the key factors that reduce
      morbidity and mortality.

PMID- 29360093
TI  - Discussion about Visual Dependence in Balance Control: European Society for
      Clinical Evaluation of Balance Disorders.
AB  - : The executive committee of the European Society for the clinical evaluation of
      balance disorders meets annually to address equilibrium problems that are not
      well understood. This is a review paper on discussions in the latest meeting we
      held. MATERIALS AND METHODS: Seeing patients with vestibular disorders who end up
      depending on visual information as part of their compensation process is a common
      clinical occurrence. However, this "visual dependence" can generate symptoms,
      which include nausea, sensations of imbalance, and anxiety. It is unclear how
      this develops, as symptoms can be widely variable from patient to patient. There
      are several triggering factors to this symptom set, and quantifying it in a given
      patient is extremely difficult Results: The committee agreed that the presence of
      this symptom set can be suggestive of vestibular pathology, but the pathology
      does not have to be present. As a result, there is no correlation between symptom
      severity and test results. CONCLUSION: Visual dependence can often be present in
      a patient, although little, if any, measurable pathology is present. It is
      important to emphasize that although we cannot accurately measure this with
      either standardized testing or pertinent questionnaires, "hypersensitive"
      patients have a genuine disease and their symptoms are not of psychiatric origin.

PMID- 29360094
TI  - Moderate-Severe Hearing Loss in Children: A Diagnostic and Rehabilitative
      Challenge.
AB  - Hearing loss in children represents a relevant topic, which needs an increasing
      attention by clinicians and researchers. Unfortunately, most cases of hearing
      loss still remain idiopathic (most frequently reported causes are genetic,
      infectious, toxic). An early diagnosis is crucial, as if not properly recognized,
      hearing disorders may impact negatively on children development and on quality of
      life. Literature data show that also children with mild-moderate, or even
      monolateral, hearing loss may present learning or verbal language disorders, if
      not adequately managed. The diagnostic work-up of hearing loss in children, which
      starts with universal neonatal hearing screening at birth, is complex, has to
      define hearing threshold, and, when possible, its etiology, often by
      multidisciplinary approach. At the same time, the audiological follow-up of those
      affected by moderate-severe hearing loss must be tight, as it is necessary to
      verify constantly: (i) hearing threshold levels, (ii) adequateness of hearing
      aids fitting, and (iii) language development. This review focuses specifically on
      the diagnostic work-up and the rehabilitative features of moderate-severe hearing
      loss in children.

PMID- 29360095
TI  - Cochleovestibular Transient Ischemic Attack as a Manifestation of Patent Foramen
      Ovale.
AB  - Paradoxical embolization is the most commonly proposed mechanism for ischemia in
      patients with patent foramen ovale (PFO). We hypothesize that these patients can
      experience a microembolic genesis of cochleovestibular dysfunction, with a
      peripheral vestibular syndrome and simultaneous cochlear signs. Hence, we report
      the first case in literature associating PFO and acute transitory audiovestibular
      loss, which occurred in a male who had had an ischemic mesencephalic stroke
      several months ago. The patient's history and duration of the current event of
      less than 24 hours following complete functional recovery without any damage
      highlight the vascular cause in cochleovestibular dysfunction and support the
      existence of a clinical entity that could be named "cochleovestibular transient
      ischemic attack".

PMID- 29360096
TI  - Simultaneous Contralateral Vestibular Schwannoma and Middle Ear Paraganglioma
      Tumor.
AB  - To the best of our knowledge, only 2 cases of a simultaneous contralateral
      vestibular schwannoma (VS) and middle ear paraganglioma (MEP) have previously
      been reported in literature. We report the third case observed in a 43-year-old
      male, who presented with an 11-year history of right-sided hearing loss and a 1
      year history of left-sided pulsatile tinnitus. A magnetic resonance imaging (MRI)
      showed a VS on the right side and computer tomography (CT) identified a Fisch
      type A1 paraganglioma on the left side. The VS was treated using a
      translabyrinthine approach and the MEP was kept under radiological observation
      for 1 year. Due to the growth of the MEP (Fisch type A2), it was treated with
      excision via a retroauricular approach. Our case was very challenging because
      there was a different and important pathology on each side, both carrying a risk
      of deafness as a consequence of the disease and/or the treatments.

PMID- 29360097
TI  - Renunciation of health care by people living with HIV in France is still
      associated with discrimination in health-care services and social insecurity -
      results from the ANRS-VESPA2 survey.
AB  - BACKGROUND: This study aimed to estimate the frequency of renunciation of health
      care among people living with HIV (PLHIV) in France, including health care
      unrelated to HIV, and to characterize associated socioeconomic and psychosocial
      risk factors. METHODS: The cross-sectional ANRS-VESPA2 survey was conducted on
      adult PLHIV attending French hospitals in 2011. Correlates of health-care
      renunciation in the 12 months before the survey were assessed through logistic
      modelling. RESULTS: Among the 3,020 PLHIV included in the sample, 17% declared
      health-care renunciation during the preceding year and 42% had a high level of
      social insecurity. During the previous 2 years, 8% and 11%, respectively, were
      discriminated against by medical staff and family. In multivariate analysis,
      positive associations were found between health-care renunciation and a high
      level of social insecurity (adjusted odds ratio [95% CI] 3.44 [2.54, 4.65];
      P<0.001), having children (1.52 [1.10, 2.10]; P=0.01), smoking tobacco (1.50
      [1.13, 1.98]; P=0.01), discrimination by medical staff (1.53 [1.22, 2.29];
      P=0.04) or family (2.48 [1.75, 3.52]; P<0.001), major depressive episodes (1.46
      [1.02, 2.09]; P=0.04), past or current drug injection (1.54 [1.03, 2.30];
      P=0.04), and younger age (0.98 [0.97, 1.00]; P=0.03). Health-care renunciation
      was also negatively associated with HIV diagnosis after 1996 (1996-2002: 0.64
      [0.46, 0.90]; P=0.01; >=2003: 0.56 [0.40, 0.77]; P=0.001). CONCLUSIONS: In spite
      of universal health insurance in France, barrier- and refusal-renunciation of
      health care by PLHIV remain frequent. Poor psychosocial outcomes and
      discrimination by families and health-care providers compound the negative effect
      of social insecurity on health-care seeking in this population. To ensure optimal
      medical care, strategies are needed to prevent discrimination against PLHIV in
      health-care services. Special attention must be provided to patients experiencing
      social insecurity.

PMID- 29360098
TI  - Dependence of subject-specific parameters for a fast helical CT respiratory
      motion model on breathing rate: an animal study.
AB  - To determine if the parameters relating lung tissue displacement to a breathing
      surrogate signal in a previously published respiratory motion model vary with the
      rate of breathing during image acquisition. An anesthetized pig was imaged using
      multiple fast helical scans to sample the breathing cycle with simultaneous
      surrogate monitoring. Three datasets were collected while the animal was
      mechanically ventilated with different respiratory rates: 12 bpm (breaths per
      minute), 17 bpm, and 24 bpm. Three sets of motion model parameters describing the
      correspondences between surrogate signals and tissue displacements were
      determined. The model error was calculated individually for each dataset, as well
      asfor pairs of parameters and surrogate signals from different experiments. The
      values of one model parameter, a vector field denoted [Formula: see text] which
      related tissue displacement to surrogate amplitude, determined for each
      experiment were compared. The mean model error of the three datasets was 1.00  +/
      0.36 mm with a 95th percentile value of 1.69 mm. The mean error computed from
      all combinations of parameters and surrogate signals from different datasets was
      1.14  +/-  0.42 mm with a 95th percentile of 1.95 mm. The mean difference in
      [Formula: see text] over all pairs of experiments was 4.7%  +/-  5.4%, and the
      95th percentile was 16.8%. The mean angle between pairs of [Formula: see text]
      was 5.0  +/-  4.0 degrees, with a 95th percentile of 13.2 mm. The motion model
      parameters were largely unaffected by changes in the breathing rate during image
      acquisition. The mean error associated with mismatched sets of parameters and
      surrogate signals was 0.14 mm greater than the error achieved when using
      parameters and surrogate signals acquired with the same breathing rate, while
      maximum respiratory motion was 23.23 mm on average.

PMID- 29360099
TI  - Electronic structure and magnetic properties of Pr-Co intermetallics: ab initio
      FP-LAPW calculations and correlation with experiments.
AB  - First-principle calculations combining density functional theory and the full
      potential linearized augmented plane wave (FP-LAPW) method are performed to
      investigate the electronic and magnetic structure of Pr2Co7 in its two
      polymorphic forms, (2:7 H) and (2:7 R), for the first time. This type of
      calculation was also performed for PrCo5 and PrCo2 intermetallics. We have
      computed the valence density of states separately for spin-up and spin-down
      states in order to investigate the electronic band structure. This is governed by
      the strong contribution of the partial DOS of 3d-Co bands compared to the partial
      DOS of the 4f-Pr bands. Such a high ferromagnetic state is discussed in terms of
      the strong spin polarization observed in the total DOS. The magnetic moments
      carried by the Co and Pr atoms located in several sites for all compounds are
      computed. These results mainly indicate that cobalt atoms make a dominant
      contribution to the magnetic moments. The notable difference in the atomic
      moments of Pr and Co atoms between different structural slabs is explained in
      terms of the magnetic characteristics of the PrCo2 and PrCo5 compounds and the
      local chemical environments of the Pr and Co atoms in different structural slabs
      of Pr2Co7. From spin-polarized calculations we have simulated the 3d and 4f band
      population to estimate the local magnetic moments. These results are in
      accordance with the magnetic moments calculated using the FP-LAPW method. In
      addition, the exchange interactions J ij are calculated and used as input for
      M(T) simulations. Involving the data obtained from the electronic structure
      calculations, the appropriate Pade Table is applied to simulate the magnetization
      M(T) and to estimate the mean-field Curie temperature. We report a fairly good
      agreement between the ab initio calculation of magnetization and Curie
      temperature with the experimental data.

PMID- 29360100
TI  - A model for the integration of conflicting exogenous and endogenous signals by
      dendritic cells.
AB  - Cells of the immune system are confronted with opposing pro- and anti
      inflammatory signals. Dendritic cells (DC) integrate these cues to make informed
      decisions whether to initiate an immune response. Confronted with exogenous
      microbial stimuli, DC endogenously produce both anti- (IL-10) and pro
      inflammatory (TNFalpha) cues whose joint integration controls the cell's final
      decision. Backed by experimental measurements we present a theoretical model to
      quantitatively describe the integration mode of these opposing signals. We
      propose a two step integration model that modulates the effect of the two types
      of signals: an initial bottleneck integrates both signals (IL-10 and TNFalpha),
      the output of which is later modulated by the anti-inflammatory signal. We show
      that the anti-inflammatory IL-10 signaling is long ranged, as opposed to the
      short-ranged pro-inflammatory TNFalpha signaling. The model suggests that the
      population averaging and modulation of the pro-inflammatory response by the anti
      inflammatory signal is a safety guard against excessive immune responses.

PMID- 29360101
TI  - 6,7-dimethoxy-coumarin as a probe of hydration dynamics in biologically relevant
      systems.
AB  - Coumarin derivatives are well known fluorescence reporters for investigating
      biological systems due to their strong micro-environment sensitivity. Despite
      having wide range of environment sensitive fluorescence probes, the potential of
      6,7-dimethoxy-coumarin has not been studied extensively so far. With a
      perspective of its use in protein studies, namely using the unnatural amino acid
      technology or as a substrate for hydrolase enzymes, we study acetyloxymethyl-6,7
      dimethoxycoumarin (Ac-DMC). We investigate the photophysics and hydration
      dynamics of this dye in aerosol-OT (AOT) reverse micelles at various water
      contents using the time dependent fluorescence shift (TDFS) method. The TDFS
      response in AOT reverse micelles from water/surfactant ratio of 0 to 20 confirms
      its sensitivity towards the hydration and mobility of its microenvironment.
      Moreover, we show that the fluorophore can be efficiently quenched by halide
      ions. Hence, we conclude that the 6,7-dimethoxy-methylcoumarin fluorophore is
      useful for studying hydration parameters in biologically relevant systems.

PMID- 29360102
TI  - Treatment of colorectal injuries in the civil war and the factors affecting
      mortality.
AB  - AIM: Colorectal injuries are one of the most common causes of mortality in war.
      Mainstay treatment of these injuries include primary repair or stoma creation.
      METHODS: Clinical data of the patients were evaluated retrospectively. Time from
      injury to hospital admission, method of treatment, the colorectal area affected,
      injury severity score ISS, hemodynamic instability, and mortality rate were
      determined. RESULTS: Of the 61 patients included in the study. Mean time from
      injury to hospital admission was 160+/-19 minutes. The injury was in the right
      colon in 24 patients 39.3%, in the left colon in 18 29.5%, and in the rectum in
      19 31.2% patients. Median ISS value of 61 patients was 16, IQR 5. Mortality and
      complication rates were higher in patients with hemodynamic instability and stoma
      requirement was also higher in this group p<0.05. Total mortality occurred in 15
      24.5% patients. Of these, 10 66.6% patients had hemodynamic instability.
      DISCUSSION: Hemodynamic instability is the most important factor affecting the
      mortality and the treatment method in wartime colorectal injuries. CONCLUSION: We
      believe that in victims of war with colorectal injuries, surgical intervention
      before the development of hemodynamic instability may reduce the rate of
      mortality and stoma requirement. KEY WORDS: Colorectal injury, Firearm injury,
      Hemodynamic instability, Stoma.

PMID- 29360103
TI  - Introducing the Global Register of Introduced and Invasive Species.
AB  - Harmonised, representative data on the state of biological invasions remain
      inadequate at country and global scales, particularly for taxa that affect
      biodiversity and ecosystems. Information is not readily available in a form
      suitable for policy and reporting. The Global Register of Introduced and Invasive
      Species (GRIIS) provides the first country-wise checklists of introduced
      (naturalised) and invasive species. GRIIS was conceived to provide a sustainable
      platform for information delivery to support national governments. We outline the
      rationale and methods underpinning GRIIS, to facilitate transparent, repeatable
      analysis and reporting. Twenty country checklists are presented as exemplars;
      GRIIS Checklists for close to all countries globally will be submitted through
      the same process shortly. Over 11000 species records are currently in the 20
      country exemplars alone, with environmental impact evidence for just over 20% of
      these. GRIIS provides significant support for countries to identify and
      prioritise invasive alien species, and establishes national and global baselines.
      In future this will enable a global system for sustainable monitoring of trends
      in biological invasions that affect the environment.

PMID- 29360104
TI  - Design and implementation of multi-signal and time-varying neural
      reconstructions.
AB  - Several efficient procedures exist to digitally trace neuronal structure from
      light microscopy, and mature community resources have emerged to store, share,
      and analyze these datasets. In contrast, the quantification of intracellular
      distributions and morphological dynamics is not yet standardized. Current
      widespread descriptions of neuron morphology are static and inadequate for
      subcellular characterizations. We introduce a new file format to represent
      multichannel information as well as an open-source Vaa3D plugin to acquire this
      type of data. Next we define a novel data structure to capture morphological
      dynamics, and demonstrate its application to different time-lapse experiments.
      Importantly, we designed both innovations as judicious extensions of the classic
      SWC format, thus ensuring full back-compatibility with popular visualization and
      modeling tools. We then deploy the combined multichannel/time-varying
      reconstruction system on developing neurons in live Drosophila larvae by
      digitally tracing fluorescently labeled cytoskeletal components along with
      overall dendritic morphology as they changed over time. This same design is also
      suitable for quantifying dendritic calcium dynamics and tracking arbor-wide
      movement of any subcellular substrate of interest.

PMID- 29360105
TI  - The impact of new transportation modes on population distribution in Jing-Jin-Ji
      region of China.
AB  - This paper conducts a novel study in China's Jing-Jin-Ji region to investigate
      the determinants of population distribution and short-term migration based on a
      comprehensive dataset including traditional census data, earth observation data,
      and emerging Internet data. Our results show that due to the high level of
      urbanization in this region, natural conditions are no longer the strongest
      determinants of population distribution. New transportation modes, such as high
      speed rail, have arisen as a significant determinant of population distribution
      and short-term migration, particularly in large cities. Socio-economic factors
      such as GDP, investment, urbanization level, and technology, which are
      traditionally assumed to govern population distribution and short-term migration,
      have less influence although education still remains an important factor
      affecting population distribution. These findings will contribute valuable
      information to regional planning decision-making in the Jing-Jin-Ji region.

PMID- 29360106
TI  - Structure of the human activated spliceosome in three conformational states.
AB  - During each cycle of pre-mRNA splicing, the pre-catalytic spliceosome (B complex)
      is converted into the activated spliceosome (Bact complex), which has a well
      formed active site but cannot proceed to the branching reaction. Here, we present
      the cryo-EM structure of the human Bact complex in three distinct conformational
      states. The EM map allows atomic modeling of nearly all protein components of the
      U2 small nuclear ribonucleoprotein (snRNP), including three of the SF3a complex
      and seven of the SF3b complex. The structure of the human Bact complex contains
      52 proteins, U2, U5, and U6 small nuclear RNA (snRNA), and a pre-mRNA. Three
      distinct conformations have been captured, representing the early, mature, and
      late states of the human Bact complex. These complexes differ in the orientation
      of the Switch loop of Prp8, the splicing factors RNF113A and NY-CO-10, and most
      components of the NineTeen complex (NTC) and the NTC-related complex. Analysis of
      these three complexes and comparison with the B and C complexes reveal an ordered
      flux of components in the B-to-Bact and the Bact-to-B* transitions, which
      ultimately prime the active site for the branching reaction.

PMID- 29360108
TI  - Commentary: But Is It really Art? The Classification of Images as "Art"/"Not Art"
      and Correlation with Appraisal and Viewer Interpersonal Differences.

PMID- 29360109
TI  - Corrigendum to "Does Comorbidity Increase the Risk of Dengue Hemorrhagic Fever
      and Dengue Shock Syndrome?"
AB  - [This corrects the article DOI: 10.1155/2013/139273.].

PMID- 29360111
TI  - Corrigendum to "The Severity of Retinopathy in the Extremely Premature Infants".
AB  - [This corrects the article DOI: 10.1155/2017/4781279.].

PMID- 29360110
TI  - Size Control and Fluorescence Labeling of Polydopamine Melanin-Mimetic
      Nanoparticles for Intracellular Imaging.
AB  - As synthetic analogs of the natural pigment melanin, polydopamine nanoparticles
      (NPs) are under active investigation as non-toxic anticancer photothermal agents
      and as free radical scavenging therapeutics. By analogy to the widely adopted
      polydopamine coatings, polydopamine NPs offer the potential for facile aqueous
      synthesis and incorporation of (bio)functional groups under mild temperature and
      pH conditions. However, clear procedures for the convenient and reproducible
      control of critical NP properties such as particle diameter, surface charge, and
      loading with functional molecules have yet to be established. In this work, we
      have synthesized polydopamine-based melanin-mimetic nanoparticles (MMNPs) with
      finely controlled diameters spanning ~25 to 120 nm and report on the pH
      dependence of zeta potential, methodologies for PEGylation, and the incorporation
      of fluorescent organic molecules. A comprehensive suite of complementary
      techniques, including dynamic light scattering (DLS), cryogenic transmission
      electron microscopy (cryo-TEM), X-ray photoelectron spectroscopy (XPS), zeta
      potential, ultraviolet-visible (UV-Vis) absorption and fluorescence spectroscopy,
      and confocal microscopy, was used to characterize the MMNPs and their properties.
      Our PEGylated MMNPs are highly stable in both phosphate-buffered saline (PBS) and
      in cell culture media and exhibit no cytotoxicity up to at least 100 MUg mL-1
      concentrations. We also show that a post-functionalization methodology for
      fluorophore loading is especially suitable for producing MMNPs with stable
      fluorescence and significantly narrower emission profiles than previous reports,
      suggesting they will be useful for multimodal cell imaging. Our results pave the
      way towards biomedical imaging and possibly drug delivery applications, as well
      as fundamental studies of MMNP size and surface chemistry dependent cellular
      interactions.

PMID- 29360112
TI  - Corrigendum to "Seroprevalence of Dengue IgG Antibodies among Healthy Adult
      Population in Lahore, Pakistan".
AB  - [This corrects the article DOI: 10.1155/2013/521396.].

PMID- 29360113
TI  - Exploring radiative and nonradiative decay paths in indole, isoindole, quinoline,
      and isoquinoline.
AB  - Radiative and nonradiative decay paths from the first excited singlet electronic
      state (S1) in four heteroaromatics, indole, isoindole, quinoline, and
      isoquinoline, were systematically explored. Three decay processes, i.e., internal
      conversion (IC), intersystem crossing (ISC), and fluorescence emission (FE), were
      compared. Minimum energy conical intersection structures between the electronic
      ground and first excited states were investigated to determine the most preferred
      IC path. The minimum energy seam of crossing (MESX) geometries between S1 and the
      lowest-lying triplet states and the spin-orbit couplings at these MESX structures
      were computed to identify the most feasible ISC path. The oscillator strength was
      calculated at each S1 local minimum to reveal the contribution of the FE process.
      The calculations clearly showed that indole had the highest fluorescent quantum
      yield, consistent with the experimental data. The present calculations also
      explained other experimental properties of the heteroaromatics such as ISC
      quantum yields.

PMID- 29360114
TI  - Correction: TiO2/vanadate (Sr10V6O25, Ni3V2O8, Zn2V2O7) heterostructured
      photocatalysts with enhanced photocatalytic activity for photoreduction of CO2
      into CH4.
AB  - Correction for 'TiO2/vanadate (Sr10V6O25, Ni3V2O8, Zn2V2O7) heterostructured
      photocatalysts with enhanced photocatalytic activity for photoreduction of CO2
      into CH4' by Yabin Yan et al., Nanoscale, 2016, 8, 949-958.

PMID- 29360115
TI  - Modeling in environmental chemistry.

PMID- 29360107
TI  - Erratum: Sequence data and association statistics from 12,940 type 2 diabetes
      cases and controls.
AB  - This corrects the article DOI: 10.1038/sdata.2017.179.

PMID- 29360116
TI  - Responses of deposition and bioaccumulation in the Great Lakes region to policy
      and other large-scale drivers of mercury emissions.
AB  - Mercury (Hg) emissions pose a global problem that requires global cooperation for
      a solution. However, neither emissions nor regulations are uniform world-wide,
      and hence the impacts of regulations are also likely to vary regionally. We
      report here an approach to model the effectiveness of regulations at different
      scales (local, regional, global) in reducing Hg deposition and fish Hg
      concentrations in the Laurentian Great Lakes (GL) region. The potential effects
      of global change on deposition are also modeled. We focus on one of the most
      vulnerable communities within the region, an Indigenous tribe in Michigan's Upper
      Peninsula (UP) with a high fish consumption rate. For the GL region, elements of
      global change (climate, biomass burning, land use) are projected to have modest
      impacts (<5% change from the year 2000) on Hg deposition. For this region, our
      estimate of the effects of elimination of anthropogenic emissions is a 70%
      decrease in deposition, while our minimal regulation scenario increases emissions
      by 35%. Existing policies have the potential to reduce deposition by 20% with
      most of the reduction attributable to U.S. policies. Local policies within the
      Great Lakes region show little effect, and global policy as embedded in the
      Minamata Convention is projected to decrease deposition by approximately 2.8%.
      Even within the GL region, effects of policy are not uniform; areas close to
      emission sources (Illinois, Indiana, Ohio, Pennsylvania) experience larger
      decreases in deposition than other areas including Michigan's UP. The UP
      landscape is highly sensitive to Hg deposition, with nearly 80% of lakes
      estimated to be impaired. Sensitivity to mercury is caused primarily by the
      region's abundant wetlands. None of the modeled policy scenarios are projected to
      reduce fish Hg concentrations to the target that would be safe for the local
      tribe. Regions like Michigan's UP that are highly sensitive to mercury deposition
      and that will see little reduction in deposition due to regulations require more
      aggressive policies to reduce emissions to achieve recovery. We highlight
      scientific uncertainties that continue to limit our ability to accurately predict
      fish Hg changes over time.

PMID- 29360117
TI  - Photophysics and peripheral ring size dependent aggregate emission of cross
      conjugated enediynes: applications to white light emission and vapor sensing.
AB  - Photophysical understanding of organic fluorophores with pi-conjugated scaffolds
      is crucial as such dyes are central to optoelectronic applications. This work
      presents a detailed photophysical investigation of a class of cross-conjugated
      homo- and hetero-enediynes (Y-shaped) peripherally attached to common aromatic
      moieties such as benzene, naphthalene, and anthracene. The cross-communicated
      electronic communication among the three aromatic units located at the tri-poles
      of the Y-shaped enediynes results in a broad S0 -> S1 absorption band and locally
      excited (LE) emission signals. In addition to the LE emission band, a red-shifted
      aggregate emission is observed for some of the dyes in non-aqueous solvents where
      a clear size dependence of the peripheral aromatic rings is noted for the
      appearance of the aggregate fluorescence. The aggregates are static in nature as
      is evident from ground-state absorption spectral changes and the absence of rise
      time in the time-resolved fluorescence decay studies, which are substantiated
      further through nuclear magnetic resonance spectroscopy and single-crystal X-ray
      diffraction experiments. Molecular orbital calculations support the local nature
      of the dominant electronic transition. The optimized ground state geometries of
      the dyes from partially to fully propeller shaped structures confirm the ring
      size dependence of the aggregates. The LE and aggregate state emissions are
      judiciously exploited to generate single-component white light emission in binary
      solvent mixtures. The excited state photophysics are further applied toward polar
      aprotic vapor sensing in the solid state.

PMID- 29360119
TI  - Strong spin-orbit interaction and magnetotransport in semiconductor Bi2O2Se
      nanoplates.
AB  - Semiconductor Bi2O2Se nanolayers of high crystal quality have been realized via
      epitaxial growth. These two-dimensional (2D) materials possess excellent electron
      transport properties with potential application in nanoelectronics. It is also
      strongly expected that the 2D Bi2O2Se nanolayers can be an excellent material
      platform for developing spintronic and topological quantum devices if the
      presence of strong spin-orbit interaction in the 2D materials can be
      experimentally demonstrated. Herein, we report the experimental determination of
      the strength of spin-orbit interactions in Bi2O2Se nanoplates through
      magnetotransport measurements. The nanoplates are epitaxially grown by chemical
      vapor deposition, and the magnetotransport measurements are performed at low
      temperatures. The measured magnetoconductance exhibits a crossover behavior from
      weak antilocalization to weak localization at low magnetic fields with increasing
      temperature or decreasing back gate voltage. We have analyzed this transition
      behavior of magnetoconductance based on an interference theory, which describes
      quantum correction to the magnetoconductance of a 2D system in the presence of
      spin-orbit interaction. Dephasing length and spin relaxation length are extracted
      from the magnetoconductance measurements. Compared to the case of other
      semiconductor nanostructures, the extracted relatively short spin relaxation
      length of ~150 nm indicates the existence of a strong spin-orbit interaction in
      Bi2O2Se nanolayers.

PMID- 29360118
TI  - Multiple single cell screening and DNA MDA amplification chip for oncogenic
      mutation profiling.
AB  - The oncogenic mutation heterogeneity of the cancer cell population has been
      proven to be essential for predicting both drug-response and drug-resistance of
      targeted therapies, such as tyrosine kinase inhibitors. It is necessary to
      accurately evaluate the mutation heterogeneity, oncogenic mutation and resistant
      mutation profiling at a single cell level. However, there are two major hurdles
      in the process. First, majority of the cells in tumor tissue are non-cancer
      cells, which cause background noise. Second, the work load and cost of next
      generation sequencing on dozens of single cells are prohibitive. To address both
      these issues, we developed a microfluidic chip for profiling of dozens of
      selected cells. With the help of a novel tri-states valve structure, which
      performs precise controlling of the cell/reagent movement, as well as active
      mixing of different reagents, trapping/identification/lysis and in situ MDA
      amplification was achieved at a single cell level on the same chip. Using a proof
      of-concept assay mimicking EGFR targeting drug Gefitinib treatment of lung cancer
      cells, the new method was validated as capable of not only detecting the
      existence of multiple mutations, but also providing complete information of the
      mutation scenario at the single cell level by using cost-effective Sanger's
      sequencing.

PMID- 29360120
TI  - Secondary relaxation in ultrastable etoricoxib: evidence of correlation with
      structural relaxation.
AB  - Secondary relaxations are fundamental for their impact in the properties of
      glasses and for their inseparable connection to the structural relaxation.
      Understanding their density dependence and aging behavior is key to fully address
      the nature of glasses. Ultrastable glasses establish a new benchmark to study the
      characteristics of secondary relaxations, since their enthalpy and density levels
      are unattainable by other routes. Here, we use dielectric spectroscopy at ambient
      and elevated pressures to study the characteristics of the secondary relaxation
      in ultrastable etoricoxib, reporting a 71% decrease in dielectric strength and
      one decade increase in relaxation time compared to the ordinary glass.
      Interestingly, we find an unprecedented connection between secondary and
      structural relaxations in ultrastable etoricoxib in exactly the same manner as in
      the ordinary glass, manifested through different properties, such as aging and
      devitrification. These results further support and extend the general validity of
      the connection between the secondary and structural relaxation.

PMID- 29360122
TI  - Substrate-orientation dependent epitaxial growth of highly ordered diamond
      nanosheet arrays by chemical vapor deposition.
AB  - Three-dimensional ordering of two-dimensional nanomaterials has long been a
      challenge. Simultaneously, diamond nanomaterials are difficult to synthesize due
      to the harsh synthesizing conditions required. Here, we report substrate-crystal
      orientation dependent growth of diamond nanosheets (DNSs) by chemical vapor
      deposition, which generates different DNS arrays on different substrates. The
      DNSs are grown by the in-plane epitaxy of the diamond {111} planes. So the arrays
      are highly ordered and solely determined by the spatial orientation of the {111}
      planes in the diamond FCC structure. The DNSs grown on the {110}, {111}, {001},
      and {113} oriented substrates show inclination angles ranging from 90 to 29.5
      degrees . The DNSs with larger inclination angles grow preferentially, forming
      parallelogram arrays with inclination angles of 90 degrees  on the {110}
      substrates and parallel-line arrays with inclination angles of 80 degrees  on the
      {113} substrates. The density, thickness, size, and morphology of the DNSs have
      been well controlled. The present understanding and materials are highly
      promising for many applications such as sensors, catalysis, photonics, thermal
      management, and electronics.

PMID- 29360121
TI  - Why does the Y326I mutant of monoamine oxidase B decompose an endogenous
      amphetamine at a slower rate than the wild type enzyme? Reaction step elucidated
      by multiscale molecular simulations.
AB  - This work investigates the Y326I point mutation effect on the kinetics of
      oxidative deamination of phenylethylamine (PEA) catalyzed by the monoamine
      oxidase B (MAO B) enzyme. PEA is a neuromodulator capable of affecting the
      plasticity of the brain and is responsible for the mood enhancing effect caused
      by physical exercise. Due to a similar functionality, PEA is often regarded as an
      endogenous amphetamine. The rate limiting step of the deamination was simulated
      at the multiscale level, employing the Empirical Valence Bond approach for the
      quantum treatment of the involved valence states, whereas the environment
      (solvated protein) was represented with a classical force field. A comparison of
      the reaction free energy profiles delivered by simulation of the reaction in the
      wild type MAO B and its Y326I mutant yields an increase in the barrier by 1.06
      kcal mol-1 upon mutation, corresponding to a roughly 6-fold decrease in the
      reaction rate. This is in excellent agreement with the experimental kinetic
      studies. Inspection of simulation trajectories reveals possible sources of the
      point mutation effect, namely vanishing favorable electrostatic interactions
      between PEA and a Tyr326 side chain and an increased amount of water molecules at
      the active site due to the replacement of tyrosine by a less spacious isoleucine
      residue, thereby increasing the dielectric shielding of the catalytic environment
      provided by the enzyme.

PMID- 29360123
TI  - Health effects of wind turbines in working environments - a scoping review.
AB  - Objectives The wind industry is a growing economic sector, yet there is no
      overview summarizing all exposures emanating from wind turbines throughout their
      life cycle that may pose a risk for workers' health. The aim of this scoping
      review was to survey and outline the body of evidence around the health effects
      of wind turbines in working environments in order to identify research gaps and
      to highlight the need for further research. Methods A scoping review with a
      transparent and systematic procedure was conducted using a comprehensive search
      strategy. Two independent reviewers conducted most of the review steps. Results
      Twenty articles of varying methodical quality were included. Our findings of the
      included studies indicate that substances used in rotor blade manufacture (epoxy
      resin and styrene) cause skin disorders, and respectively, respiratory ailments
      and eye complaints; exposure to onshore wind turbine noise leads to annoyance,
      sleep disorders, and lowered general health; finally working in the wind industry
      is associated with a considerable accident rate, resulting in injuries or
      fatalities. Conclusions Due to the different work activities during the life
      cycle of a wind turbine and the distinction between on- and offshore work, there
      are no specific overall health effects of working in the wind sector. Previous
      research has primarily focused on evaluating the effects of working in the wind
      industry on skin disorders, accidents, and noise consequences. There is a need
      for further research, particularly in studying the effect of wind turbine work on
      psychological and musculoskeletal disorders, work-related injury and accident
      rates, and health outcomes in later life cycle phases.

PMID- 29360124
TI  - ?

PMID- 29360125
TI  - ?

PMID- 29360127
TI  - ?

PMID- 29360126
TI  - ?

PMID- 29360128
TI  - ?

PMID- 29360130
TI  - ?

PMID- 29360129
TI  - ?

PMID- 29360131
TI  - ?

PMID- 29360132
TI  - ?
AB  - The ABC of atrial fibrillation at the emergency care department Atrial
      fibrillation (AF) is the most common tachyarrhythmia. When handling patients with
      AF at the emergency care department it is of utmost importance to take a
      structural approach, make the right diagnosis, take care of the risk and/or
      trigger factors, treat and make sure there is an adequate follow-up.

PMID- 29360133
TI  - ?
AB  - Correct electrode placement - a prerequisite for correct ECG interpretation
      Different lead misplacements may present with typical ECG changes, which may
      influence the management of the patient, if not identified and corrected. It is
      important, both for the ECG technician and for the interpreting physician, to
      recognize typical patterns of lead misplacement to avoid misinterpretation of the
      ECG.

PMID- 29360134
TI  - ?
AB  - The understanding of health inequalities requires further development of
      epidemiological capacity and must have a broad focus on social determinants of
      health The article by Agardh et al (1) in this issue of Lakartidningen compares
      the trend of population health in Stockholm county versus the rest of the
      country. The article represents an important attempt to monitor and understand
      the driving forces of geographical inequalities in health. However, such
      inequalities also depend heavily on migration patterns and how these are linked
      to social determinants of health. Therefore it is important to include
      determinants from a broad range of policy sectors (e.g. education, labour market,
      family welfare, as well as health care services) in order to interpret the deeper
      causes of geographic inequalities in health. Monitoring population health and
      health inequalities should be linked to a general follow-up of Agenda 2030 and a
      sustainable development.

PMID- 29360135
TI  - ?
AB  - Falsely elevated plasma creatinine due to monoclonal gammopathy Analytical
      interference may give rise to falsely elevated as well as reduced clinical
      biochemical results. Hemolysis, icterus and lipemia in patient samples are well
      known causes of analytical interference. Laboratories usually automatically check
      for these interferences and take them into account. However, other causes of
      interference are more difficult to detect, such as those caused by heterophilic
      antibodies and in this case a falsely elevated plasma creatinine level caused by
      a monoclonal IgM gammopathy. Analytical interference should be considered in
      cases with unexpected laboratory results and inconsistent pattern of results, in
      which contact and discussion with the laboratory is advised.

PMID- 29360136
TI  - ?
AB  - Previous studies in Sweden have focused on a number of indicators to assess and
      compare health conditions at regional levels over time. In this study we aimed to
      give a more complete picture of the health situation in Stockholm County compared
      to the rest of Sweden, by using the DALY measure (disability-adjusted life
      years). DALY combines life lost to premature death (YLL) and years lived with
      disability (YLD) in one measure, and also allow comparisons of fatal and non
      fatal conditions. This approach reveals that low back and neck pain and ischemic
      heart disease dominated the disease burden in 2015. Moreover, the health progress
      in Stockholm County has been better than the rest of Sweden since 1990, and the
      main reason is the decrease in premature death (YLL). This can partly be
      explained by a decrease in risk factors such as unhealthy diets, high blood
      pressure, tobacco smoking, high BMI and physical inactivity. The development of
      YLD has been relatively constant since 1990 in both Stockholm County and the rest
      of Sweden, implying that Sweden has been more successful in preventing death than
      reducing disability.

PMID- 29360137
TI  - cHCC-CCA: Consensus terminology for primary liver carcinomas with both
      hepatocytic and cholangiocytic differentation.
AB  - : Primary liver carcinomas with both hepatocytic and cholangiocytic
      differentiation have been referred to as "combined (or mixed) hepatocellular
      cholangiocarcinoma." These tumors, although described over 100 years ago, have
      attracted greater attention recently because of interest in possible stem cell
      origin and perhaps because of greater frequency and clinical recognition.
      Currently, because of a lack of common terminology in the literature, effective
      treatment and predictable outcome data have been challenging to accrue. This
      article represents a consensus document from an international community of
      pathologists, radiologists, and clinicians who have studied and reported on these
      tumors and recommends a working terminology for diagnostic and research
      approaches for further study and evaluation. CONCLUSION: It is recommended that
      diagnosis is based on routine histopathology with hematoxylin and eosin (H&E);
      immunostains are supportive, but not essential for diagnosis. (Hepatology
      2018;68:113-126).

PMID- 29360138
TI  - Interventions to reduce acute and late adverse gastrointestinal effects of pelvic
      radiotherapy for primary pelvic cancers.
AB  - BACKGROUND: An increasing number of people survive cancer but a significant
      proportion have gastrointestinal side effects as a result of radiotherapy (RT),
      which impairs their quality of life (QoL). OBJECTIVES: To determine which
      prophylactic interventions reduce the incidence, severity or both of adverse
      gastrointestinal effects among adults receiving radiotherapy to treat primary
      pelvic cancers. SEARCH METHODS: We conducted searches of CENTRAL, MEDLINE, and
      Embase in September 2016 and updated them on 2 November 2017. We also searched
      clinical trial registries. SELECTION CRITERIA: We included randomised controlled
      trials (RCTs) of interventions to prevent adverse gastrointestinal effects of
      pelvic radiotherapy among adults receiving radiotherapy to treat primary pelvic
      cancers, including radiotherapy techniques, other aspects of radiotherapy
      delivery, pharmacological interventions and non-pharmacological interventions.
      Studies needed a sample size of 20 or more participants and needed to evaluate
      gastrointestinal toxicity outcomes. We excluded studies that evaluated dosimetric
      parameters only. We also excluded trials of interventions to treat acute
      gastrointestinal symptoms, trials of altered fractionation and dose escalation
      schedules, and trials of pre- versus postoperative radiotherapy regimens, to
      restrict the vast scope of the review. DATA COLLECTION AND ANALYSIS: We used
      standard Cochrane methodology. We used the random-effects statistical model for
      all meta-analyses, and the GRADE system to rate the certainty of the evidence.
      MAIN RESULTS: We included 92 RCTs involving more than 10,000 men and women
      undergoing pelvic radiotherapy. Trials involved 44 different interventions,
      including radiotherapy techniques (11 trials, 4 interventions/comparisons), other
      aspects of radiotherapy delivery (14 trials, 10 interventions), pharmacological
      interventions (38 trials, 16 interventions), and non-pharmacological
      interventions (29 trials, 13 interventions). Most studies (79/92) had design
      limitations. Thirteen studies had a low risk of bias, 50 studies had an unclear
      risk of bias and 29 studies had a high risk of bias. Main findings include the
      following:Radiotherapy techniques: Intensity-modulated radiotherapy (IMRT) versus
      3D conformal RT (3DCRT) may reduce acute (risk ratio (RR) 0.48, 95% confidence
      interval (CI) 0.26 to 0.88; participants = 444; studies = 4; I2 = 77%; low
      certainty evidence) and late gastrointestinal (GI) toxicity grade 2+ (RR 0.37,
      95% CI 0.21 to 0.65; participants = 332; studies = 2; I2 = 0%; low-certainty
      evidence). Conformal RT (3DCRT or IMRT) versus conventional RT reduces acute GI
      toxicity grade 2+ (RR 0.57, 95% CI 0.40 to 0.82; participants = 307; studies = 2;
      I2 = 0%; high-certainty evidence) and probably leads to less late GI toxicity
      grade 2+ (RR 0.49, 95% CI 0.22 to 1.09; participants = 517; studies = 3; I2 =
      44%; moderate-certainty evidence). When brachytherapy (BT) is used instead of
      external beam radiotherapy (EBRT) in early endometrial cancer, evidence indicates
      that it reduces acute GI toxicity (grade 2+) (RR 0.02, 95% CI 0.00 to 0.18;
      participants = 423; studies = 1; high-certainty evidence).Other aspects of
      radiotherapy delivery: There is probably little or no difference in acute GI
      toxicity grade 2+ with reduced radiation dose volume (RR 1.21, 95% CI 0.81 to
      1.81; participants = 211; studies = 1; moderate-certainty evidence) and maybe no
      difference in late GI toxicity grade 2+ (RR 1.02, 95% CI 0.15 to 6.97;
      participants = 107; studies = 1; low-certainty evidence). Evening delivery of RT
      may reduce acute GI toxicity (diarrhoea) grade 2+ during RT compared with morning
      delivery of RT (RR 0.51, 95% CI 0.34 to 0.76; participants = 294; studies = 2; I2
      = 0%; low-certainty evidence). There may be no difference in acute (RR 2.22, 95%
      CI 0.62 to 7.93, participants = 110; studies = 1) and late GI toxicity grade 2+
      (RR 0.44, 95% CI 0.12 to 1.65; participants = 81; studies = 1) between a bladder
      volume preparation of 1080 mls and that of 540 mls (low-certainty evidence). Low
      certainty evidence on balloon and hydrogel spacers suggests that these
      interventions for prostate cancer RT may make little or no difference to GI
      outcomes.Pharmacological interventions: Evidence for any beneficial effects of
      aminosalicylates, sucralfate, amifostine, corticosteroid enemas, bile acid
      sequestrants, famotidine and selenium is of a low or very low certainty. However,
      evidence on certain aminosalicylates (mesalazine, olsalazine), misoprostol
      suppositories, oral magnesium oxide and octreotide injections suggests that these
      agents may worsen GI symptoms, such as diarrhoea or rectal bleeding.Non
      pharmacological interventions: Low-certainty evidence suggests that protein
      supplements (RR 0.23, 95% CI 0.07 to 0.74; participants = 74; studies = 1),
      dietary counselling (RR 0.04, 95% CI 0.00 to 0.60; participants = 74; studies =
      1) and probiotics (RR 0.43, 95% CI 0.22 to 0.82; participants = 923; studies = 5;
      I2 = 91%) may reduce acute RT-related diarrhoea (grade 2+). Dietary counselling
      may also reduce diarrhoeal symptoms in the long term (at five years, RR 0.05, 95%
      CI 0.00 to 0.78; participants = 61; studies = 1). Low-certainty evidence from one
      study (108 participants) suggests that a high-fibre diet may have a beneficial
      effect on GI symptoms (mean difference (MD) 6.10, 95% CI 1.71 to 10.49) and
      quality of life (MD 20.50, 95% CI 9.97 to 31.03) at one year. High-certainty
      evidence indicates that glutamine supplements do not prevent RT-induced
      diarrhoea. Evidence on various other non-pharmacological interventions, such as
      green tea tablets, is lacking.Quality of life was rarely and inconsistently
      reported across included studies, and the available data were seldom adequate for
      meta-analysis. AUTHORS' CONCLUSIONS: Conformal radiotherapy techniques are an
      improvement on older radiotherapy techniques. IMRT may be better than 3DCRT in
      terms of GI toxicity, but the evidence to support this is uncertain. There is no
      high-quality evidence to support the use of any other prophylactic intervention
      evaluated. However, evidence on some potential interventions shows that they
      probably have no role to play in reducing RT-related GI toxicity. More RCTs are
      needed for interventions with limited evidence suggesting potential benefits.

PMID- 29360139
TI  - Hepatic stellate cell-derived platelet-derived growth factor receptor-alpha
      enriched extracellular vesicles promote liver fibrosis in mice through SHP2.
AB  - : Liver fibrosis is characterized by the activation and migration of hepatic
      stellate cells (HSCs), followed by matrix deposition. Recently, several studies
      have shown the importance of extracellular vesicles (EVs) derived from liver
      cells, such as hepatocytes and endothelial cells, in liver pathobiology. While
      most of the studies describe how liver cells modulate HSC behavior, an important
      gap exists in the understanding of HSC-derived signals and more specifically HSC
      derived EVs in liver fibrosis. Here, we investigated the molecules released
      through HSC-derived EVs, the mechanism of their release, and the role of these
      EVs in fibrosis. Mass spectrometric analysis showed that platelet-derived growth
      factor (PDGF) receptor-alpha (PDGFRalpha) was enriched in EVs derived from PDGF
      BB-treated HSCs. Moreover, patients with liver fibrosis had increased PDGFRalpha
      levels in serum EVs compared to healthy individuals. Mechanistically, in vitro
      tyrosine720-to-phenylalanine mutation on the PDGFRalpha sequence abolished
      enrichment of PDGFRalpha in EVs and redirected the receptor toward degradation.
      Congruently, the inhibition of Src homology 2 domain tyrosine phosphatase 2, the
      regulatory binding partner of phosphorylated tyrosine720, also inhibited
      PDGFRalpha enrichment in EVs. EVs derived from PDGFRalpha-overexpressing cells
      promoted in vitro HSC migration and in vivo liver fibrosis. Finally,
      administration of Src homology 2 domain tyrosine phosphatase 2inhibitor, SHP099,
      to carbon tetrachloride-administered mice inhibited PDGFRalpha enrichment in
      serum EVs and reduced liver fibrosis. CONCLUSION: PDGFRalpha is enriched in EVs
      derived from PDGF-BB-treated HSCs in an Src homology 2 domain tyrosine
      phosphatase 2-dependent manner and these PDGFRalpha-enriched EVs participate in
      development of liver fibrosis. (Hepatology 2018;68:333-348).

PMID- 29360140
TI  - Effects of Survey Mode on Consumer Assessment of Healthcare Providers and Systems
      (CAHPS) Hospice Survey Scores.
AB  - OBJECTIVES: To examine the effect of mode of survey administration on response
      rates and response tendencies for the Consumer Assessment of Healthcare Providers
      and Systems (CAHPS) Hospice Survey and develop appropriate adjustments. DESIGN:
      Survey response data were obtained after sampling and fielding of the CAHPS
      Hospice Survey in 2015. Sampled caregivers and decedents were randomized to one
      of three modes: mail only, telephone only, and mixed mode (mail with telephone
      follow-up). Linear regression analysis was used to examine the effect of mode on
      individual responses to questions (6 composite measures and 2 global measures
      that examine hospice quality). SETTING: U.S. hospice programs (N = 57).
      PARTICIPANTS: Primary caregivers of individuals who died in hospice (N = 7,349).
      MEASUREMENTS: Outcomes were 8 hospice quality measures (6 composite measures, 2
      global measures). Analyses were adjusted for differences in case-mix (e.g.,
      decedent age, payer for hospice care, primary diagnosis, length of final episode
      of hospice care, respondent age, respondent education, relationship of decedent
      to caregiver, survey language, and language spoken at home) between hospices.
      RESULTS: Response rates were 42.6% for those randomized to mail only, 37.9%, for
      those randomized to telephone only, and 52.6% for those randomized to mixed mode
      (P < .001 for difference). There were significant mode effects (P < .05) for 10
      of the 24 questions that compose the quality measures, with mail-only respondents
      being significantly more likely to report better experiences than telephone-only
      respondents. CONCLUSION: Unlike results observed in previous mode experiments for
      hospital CAHPS, hospice primary caregivers tend to respond more negatively by
      telephone than by mail. Valid comparisons of hospice performance require that
      reported hospice scores be adjusted for survey mode.

PMID- 29360142
TI  - Baseline ICIQ-UI score, body mass index, age, average birth weight, and
      perineometry duration as promising predictors of the short-term efficacy of
      Er:YAG laser treatment in stress urinary incontinent women: A prospective cohort
      study.
AB  - BACKGROUND AND OBJECTIVE: A growing body of evidence indicates that a non
      invasive erbium yttrium-aluminum-garnet (Er:YAG) laser may be an effective and
      highly tolerable treatment for stress urinary incontinence (SUI) in women. The
      primary objective was to identify pre-intervention predictors of short-term
      Er:YAG outcomes. The secondary objective was to identify patient segments with
      the best Er:YAG laser treatment short-term outcomes. METHODS: A prospective
      cohort study performed in 2016 at Ob/Gyn Clinic, Zagreb, Croatia, recruited 85
      female patients who suffered from SUI. The intervention was performed with a 2940
      nm wave length Er:YAG laser (XS Dynamis, Fotona, Slovenia). Outcomes were
      absolute change in the International Consultation on Incontinence Questionnaire
      Short Form (ICIQ-UI SF) and a relative decrease in ICIQ-UI score of >=30% 2-6
      months after the intervention. RESULTS: Age and pre-intervention ICIQ-UI values
      were independent significant predictors of laser treatment efficacy for SUI. A
      decrease in ICIQ-UI score (minimum important difference, MID) of >=30% was
      independently significantly associated with body mass index and ICIQ-UI values
      before the intervention. All patients with four or five positive predictors saw a
      clinically relevant decrease in ICIQ-UI of >=30%. The total accuracy of the
      predictive model defined by the area under the curve was 0.83 (95%CI 0.74-0.91).
      At the cut-off >=3 positive predictors, C-index was 0.80 (95%CI 0.71-0.90),
      positive predictive value was 0.97 (95%CI 0.87-0.99), and negative predictive
      value was 0.53 (95%CI 0.45-0.55). CONCLUSIONS: A relevant decrease in ICIQ-UI
      (MID) of >=30% can be predicted based on age, body mass index, average birth
      weight, perineometer squeeze duration, and ICIQ-UI scores before the
      intervention. The association between Q-tip test and treatment outcome was
      moderated by age. Q-tip was a significant predictor for patients between 44 and
      53 years of age. The best results should be expected in younger women with a body
      mass index of <=23.3, average birth weight of >3.6 kg, ICIQ-UI at a baseline of
      <=10, and perineometer squeeze duration at a baseline of >=3.51 seconds. The
      critical age for Er:YAG laser effect is 47.5 years. Lasers Surg. Med. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29360141
TI  - Antenatal corticosteroids: a retrospective cohort study on timing, indications
      and neonatal outcome.
AB  - INTRODUCTION: An antenatal corticosteroid (ACS) delivery interval of 24 h to
      seven days is commonly referred to as optimal timing. We aimed to investigate
      whether the ACS delivery interval was associated with the obstetric indication
      for treatment and with neonatal complications. MATERIAL AND METHODS: The study
      was a retrospective chart review of clinical data from preterm neonates delivered
      at the Skane University Hospital, Lund University, Sweden, from 1 January 2013 to
      31 December 2016. The ACS delivery intervals were compared between groups of
      women with various clinical scenarios and related to neonatal outcomes. RESULTS:
      The study included 498 preterm neonates from 431 women. One to seven days before
      delivery, 41% of the women received ACS. Women with preterm prelabor rupture of
      membranes or vaginal bleeding had a median ACS delivery interval of 7.5 and eight
      days, respectively, compared with women with maternal/fetal indications or
      preterm labor (three and two days, respectively) (p < 0.001). Neonates with an
      ACS delivery interval of more than seven days were at a higher risk of
      respiratory distress syndrome [odds ratio (OR) 2.00, 95% confidence interval (CI)
      1.05-3.79] and moderate or severe bronchopulmonary dysplasia (OR 2.78, 95% CI
      1.45-5.33) than were neonates with an ACS delivery interval of one to seven days.
      CONCLUSION: Optimal timing of ACS treatment varied significantly based on the
      clinical indication. Women with preterm prelabor rupture of membranes or vaginal
      bleeding were more likely to have an ACS delivery interval of more than seven
      days. A prolonged ACS delivery interval was associated with an increased risk of
      neonatal respiratory morbidity and a prolonged stay in the neonatal care unit,
      but not with neonatal mortality.

PMID- 29360143
TI  - Long-term prognostic value of combined free triiodothyronine and late gadolinium
      enhancement in nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: Thyroid dysfunction and myocardial fibrosis are both associated with
      cardiovascular events in patients with dilated cardiomyopathy (DCM). HYPOTHESIS:
      The combination of thyroid hormone (TH) and myocardial fibrosis (detected by late
      gadolinium enhancement [LGE]) is an independent and incremental predictor of
      adverse events in DCM. METHODS: We consecutively enrolled 220 idiopathic DCM
      patients with thyroid function and LGE assessment at Fuwai Hospital (China) from
      January 2010 to October 2011 and followed up through December 2015. Patients were
      divided into 4 groups according to the presence or absence of LGE and FT3 value
      (median level of 2.79 pg/mL): LGE-positive + FT3 < 2.79 pg/mL, LGE-positive + FT3
      >= 2.79 pg/mL, LGE-negative + FT3 < 2.79 pg/mL, and LGE-negative + FT3 >= 2.79
      pg/mL. RESULTS: During a median follow-up of 61 months, 56 patients (25.5%) died,
      with 27/56 (48.2%), 8/45 (17.8%), 12/54 (22.2%), and 9/65 (13.8%) among 4 groups
      (P = 0.009), respectively. Multivariable Cox regression analysis identified LGE
      positive and FT3 < 2.79 pg/mL as a significant independent predictor of all-cause
      mortality (hazard ratio: 2.893, 95% confidence interval: 1.323-6.326, P = 0.008).
      Combining the predictive value of FT3 and LGE status significantly improved risk
      reclassification for all-cause mortality, as indicated by the net
      reclassification improvement (0.28; P = 0.005) and integrated discrimination
      improvement (0.058; P = 0.001). CONCLUSIONS: The findings suggest that the
      combination of FT3 and LGE yielded a more accurate predictive value for long-term
      prognosis in patients with DCM, which may improve patient selection for intensive
      interventions.

PMID- 29360144
TI  - Agreement between coding schemas used to identify bleeding-related
      hospitalizations in claims analyses of nonvalvular atrial fibrillation patients.
AB  - BACKGROUND: Schemas to identify bleeding-related hospitalizations in claims data
      differ in billing codes used and coding positions allowed. We assessed agreement
      across bleeding-related hospitalization coding schemas for claims analyses of
      nonvalvular atrial fibrillation (NVAF) patients on oral anticoagulation (OAC).
      HYPOTHESIS: We hypothesized that prior coding schemas used to identify bleeding
      related hospitalizations in claim database studies would provide varying levels
      of agreement in incidence rates. METHODS: Within MarketScan data, we identified
      adults, newly started on OAC for NVAF from January 2012 to June 2015. Billing
      code schemas developed by Cunningham et al., the US Food and Drug Administration
      (FDA) Mini-Sentinel program, and Yao et al. were used to identify bleeding
      related hospitalizations as a surrogate for major bleeding. Bleeds were
      subcategorized as intracranial hemorrhage (ICH), gastrointestinal (GI), or other.
      Schema agreement was assessed by comparing incidence, rates of events/100 person
      years (PYs), and Cohen's kappa statistic. RESULTS: We identified 151 738 new
      users of OAC with NVAF (CHA2DS2-VASc score = 3, [interquartile range = 2-4] and
      median HAS-BLED score = 3 [interquartile range = 2-3]). The Cunningham, FDA Mini
      Sentinel, and Yao schemas identified any bleeding-related hospitalizations in
      1.87% (95% confidence interval [CI]: 1.81-1.94), 2.65% (95% CI: 2.57-2.74), and
      4.66% (95% CI: 4.55-4.76) of patients (corresponding rates = 3.45, 4.90, and 8.65
      events/100 PYs). Kappa agreement across schemas was weak-to-moderate (kappa =
      0.47-0.66) for any bleeding hospitalization. Near-perfect agreement (kappa =
      0.99) was observed with the FDA Mini-Sentinel and Yao schemas for ICH-related
      hospitalizations, but agreement was weak when comparing Cunningham to FDA Mini
      Sentinel or Yao (kappa = 0.52-0.53). FDA Mini-Sentinel and Yao agreement was
      moderate (kappa = 0.62) for GI bleeding, but agreement was weak when comparing
      Cunningham to FDA Mini-Sentinel or Yao (kappa = 0.44-0.56). For other bleeds,
      agreement across schemas was minimal (kappa = 0.14-0.38). CONCLUSIONS: We
      observed varying levels of agreement among 3 bleeding-related hospitalizations
      schemas in NVAF patients.

PMID- 29360145
TI  - Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane
      member 16A Cl- channels.
AB  - : Bile acids stimulate a bicarbonate-rich choleresis, in part, through effects on
      cholangiocytes. Because Cl- channels in the apical membrane of cholangiocytes
      provide the driving force for secretion and transmembrane member 16A (TMEM16A)
      has been identified as the Ca2+ -activated Cl- channel in the apical membrane of
      cholangiocytes, the aim of the present study was to determine whether TMEM16A is
      the target of bile-acid-stimulated Cl- secretion and to identify the regulatory
      pathway involved. In these studies of mouse, rat, and human biliary epithelium
      exposure to ursodeoxycholic acid (UDCA) or tauroursodeoxycholic acid (TUDCA)
      rapidly increased the rate of exocytosis, ATP release, [Ca2+ ]i , membrane Cl-
      permeability, and transepithelial secretion. Bile-acid-stimulated Cl- currents
      demonstrated biophysical properties consistent with TMEM16A and were inhibited by
      pharmacological or molecular (small-interfering RNA; siRNA) inhibition of
      TMEM16A. Bile acid-stimulated Cl- currents were not observed in the presence of
      apyrase, suramin, or 2-aminoethoxydiphenyl borate (2-APB), demonstrating that
      current activation requires extracellular ATP, P2Y, and inositol 1,4,5
      trisphosphate (IP3) receptors. TUDCA did not activate Cl- currents during
      pharmacologic inhibition of the apical Na+ -dependent bile acid transporter
      (ASBT), but direct intracellular delivery of TUDCA rapidly activated Cl-
      currents. CONCLUSION: Bile acids stimulate Cl- secretion in mouse and human
      biliary cells through activation of membrane TMEM16A channels in a process
      regulated by extracellular ATP and [Ca2+ ]i . These studies suggest that TMEM16A
      channels may be targets to increase bile flow during cholestasis. (Hepatology
      2018;68:187-199).

PMID- 29360147
TI  - Carcinocythemia: First report in a cat and literature review.
AB  - A 6-year-old female neutered European Shorthair cat was presented with a 2-day
      history of lethargy and hyporexia. On physical examination, the cat was slightly
      depressed and had a 2.5 cm nodule in the left 3rd mammary gland. The hemogram
      revealed mild leukocytosis with mature neutrophilia and moderate
      thrombocytopenia. On blood smear evaluation, rare pleomorphic cells, possibly of
      epithelial origin, were observed mainly at the feathered edge. The animal died
      about 12 hours after presentation, and a necropsy was performed. On
      histopathology, the mammary nodule was diagnosed as a tubulopapillary
      adenocarcinoma with vascular invasion and widespread metastases.
      Immunocytochemical tests for cytokeratins (AE1/AE3) confirmed the epithelial
      phenotype of the neoplastic cells observed on the blood smear. The present report
      describes a feline mammary carcinoma with widespread metastases and the presence
      of malignant epithelial cells in the peripheral blood referred to as
      carcinocythemia. This condition has been previously described in people and dogs.
      To the author's knowledge, this is the first reported case of feline
      carcinocythemia. As in other species, the phenomenon was associated with a
      terminal phase of systemic malignancy.

PMID- 29360148
TI  - Na+ ,K+ /H+ antiporters regulate the pH of endoplasmic reticulum and auxin
      mediated development.
AB  - AtNHX5 and AtNHX6 are endosomal Na+ ,K+ /H+ antiporters that are critical for
      growth and development in Arabidopsis, but the mechanism behind their action
      remains unknown. Here, we report that AtNHX5 and AtNHX6, functioning as H+ leak,
      control auxin homeostasis and auxin-mediated development. We found that nhx5 nhx6
      exhibited growth variations of auxin-related defects. We further showed that nhx5
      nhx6 was affected in auxin homeostasis. Genetic analysis showed that AtNHX5 and
      AtNHX6 were required for the function of the endoplasmic reticulum (ER)-localized
      auxin transporter PIN5. Although AtNHX5 and AtNHX6 were colocalized with PIN5 at
      ER, they did not interact directly. Instead, the conserved acidic residues in
      AtNHX5 and AtNHX6, which are essential for exchange activity, were required for
      PIN5 function. AtNHX5 and AtNHX6 regulated the pH in ER. Overall, AtNHX5 and
      AtNHX6 may regulate auxin transport across the ER via the pH gradient created by
      their transport activity. H+ -leak pathway provides a fine-tuning mechanism that
      controls cellular auxin fluxes.

PMID- 29360149
TI  - Audiovisual biofeedback improves the correlation between internal/external
      surrogate motion and lung tumor motion.
AB  - PURPOSE: Breathing management can reduce breath-to-breath (intrafraction) and day
      by-day (interfraction) variability in breathing motion while utilizing the
      respiratory motion of internal and external surrogates for respiratory guidance.
      Audiovisual (AV) biofeedback, an interactive personalized breathing motion
      management system, has been developed to improve reproducibility of intra- and
      interfraction breathing motion. However, the assumption of the correlation of
      respiratory motion between surrogates and tumors is not always verified during
      medical imaging and radiation treatment. Therefore, the aim of the study was to
      test the hypothesis that the correlation of respiratory motion between surrogates
      and tumors is the same under free breathing without guidance (FB) and with AV
      biofeedback guidance for voluntary motion management. METHODS: For 13 lung cancer
      patients receiving radiotherapy, 2D coronal and sagittal cine-MR images were
      acquired across two MRI sessions (pre- and mid-treatment) with two breathing
      conditions: (a) FB and (b) AV biofeedback, totaling 88 patient measurements.
      Simultaneously, the external respiratory motion of the abdomen was measured. The
      internal respiratory motion of the diaphragm and lung tumor was retrospectively
      measured from 2D coronal and sagittal cine-MR images. The correlation of
      respiratory motion between surrogates and tumors was calculated using Pearson's
      correlation coefficient for: (a) abdomen to tumor (abdomen-tumor) and (b)
      diaphragm to tumor (diaphragm-tumor). The correlations were compared between FB
      and AV biofeedback using several metrics: abdomen-tumor and diaphragm-tumor
      correlations with/without >=5 mm tumor motion range and with/without adjusting
      for phase shifts between the signals. RESULTS: Compared to FB, AV biofeedback
      improved abdomen-tumor correlation by 11% (p = 0.12) from 0.53 to 0.59 and
      diaphragm-tumor correlation by 13% (p = 0.02) from 0.55 to 0.62. Compared to FB,
      AV biofeedback improved abdomen-tumor correlation by 17% (p = 0.01) and diaphragm
      tumor correlation by 15% (p < 0.01) while correcting 0.3 s (p = 0.54) and 0.2 s
      (p = 0.19) phase shifts, respectively. In addition, AV biofeedback with >=5 mm
      tumor motion range, compared to FB improved abdomen-tumor correlation by 14% (p =
      0.18) and diaphragm-tumor correlation by 17% (p = 0.01). The highest abdomen
      tumor and diaphragm-tumor correlations were found using >=5 mm tumor motion range
      and phase shifts, resulting in a 12% improvement in AV biofeedback. CONCLUSIONS:
      Our results demonstrated that AV biofeedback improves the correlation of
      respiratory motion between surrogates and the tumor. This suggests a need for AV
      biofeedback for respiratory guidance utilizing respiratory surrogates during
      image-guided and MRI-guided radiotherapy in thoracic regions.

PMID- 29360150
TI  - Correcting TG 119 confidence limits.
AB  - PURPOSE: Task Group 119 (TG-119) has been adopted for evaluating the adequacy of
      intensity-modulated radiation therapy (IMRT) commissioning and for establishing
      patient-specific IMRT quality assurance (QA) passing criteria in clinical
      practice. TG-119 establishes 95% confidence limits (CLs), which help clinics
      identify systematic IMRT QA errors and identify outliers. In TG-119, the 95% CLs
      are established by fitting the Gamma Gamma analysis passing rate results to an
      assumed distribution, then calculating the limit in which 95% of the data fall.
      CLs for a given dataset will depend greatly on the type of distribution used, and
      those determined by following the TG-119 guidelines are only valid if the
      underlying data follows a Gaussian distribution. Gaussian distributions assume
      symmetry about the mean, which would imply the possibility of negative Gamma
      analysis failing rates. This study demonstrates that the gamma distribution is a
      more reasonable assumption for establishing CLs than the Gaussian distribution
      used in TG-119. Thus, the gamma distribution is suggested as a replacement to the
      conventional Gaussian statistical model used in TG-119. MATERIALS AND METHODS:
      The moments estimator (ME) for the gamma family is used to obtain the CLs of the
      failing rates for all Gamma analysis criteria. To demonstrate the congruence of
      the gamma distribution, the root mean squared error and the CL values for the MEs
      of the gamma and the Gaussian families were compared. RESULTS: In this study, the
      empirical 95% CLs generated using 302 plans represent the ground truth, which
      resulted in a 91.83% passing rate using 3%/3 mm error local criteria. The gamma
      distribution underestimates the 95% CL by 0.09%, while the Gaussian distribution
      overestimates the 95% CL by 4.12%. CONCLUSIONS: Although IMRT QA equipment may
      vary between clinics, the mathematical formalism presented in this study applies
      to any combination of planning and delivery systems. This study has demonstrated
      that a gamma distribution should be favored over a Gaussian distribution when
      establishing CLs for IMRT QA.

PMID- 29360151
TI  - Compton scatter imaging: A promising modality for image guidance in lung
      stereotactic body radiation therapy.
AB  - PURPOSE: Lung stereotactic body radiation therapy (SBRT) requires delivering
      large radiation doses with millimeter accuracy, making image guidance essential.
      An approach to forming images of patient anatomy from Compton-scattered photons
      during lung SBRT is presented. METHODS: To investigate the potential of scatter
      imaging, a pinhole collimator and flat-panel detector are used for spatial
      localization and detection of photons scattered during external beam therapy
      using lung SBRT treatment conditions (6 MV FFF beam). MCNP Monte Carlo software
      is used to develop a model to simulate scatter images. This model is validated by
      comparing experimental and simulated phantom images. Patient scatter images are
      then simulated from 4DCT data. RESULTS: Experimental lung tumor phantom images
      have sufficient contrast-to-noise to visualize the tumor with as few as 10 MU
      (0.5 s temporal resolution). The relative signal intensity from objects of
      different composition as well as lung tumor contrast for simulated phantom images
      agree quantitatively with experimental images, thus validating the Monte Carlo
      model. Scatter images are shown to display high contrast between different
      materials (lung, water, bone). Simulated patient images show superior (~double)
      tumor contrast compared to MV transmission images. CONCLUSIONS: Compton scatter
      imaging is a promising modality for directly imaging patient anatomy during
      treatment without additional radiation, and it has the potential to complement
      existing technologies and aid tumor tracking and lung SBRT image guidance.

PMID- 29360154
TI  - Monte Carlo analysis of beam blocking grid design parameters: Scatter estimation
      and the importance of electron backscatter.
AB  - PURPOSE: Beam blocking grids provide a simple and direct measurement of the
      scattered photon signal which degrades image quality in x-ray imaging systems,
      such as cone-beam CT (CBCT). This study evaluates the scatter estimation accuracy
      of the beam blocking method to optimize the design parameters of the grid system
      (e.g., grid thickness, source-to-grid distance (SGD), septa width, air
      interspace, and grid ratio) using Monte Carlo (MC) simulations. METHOD: A MC
      model of a CBCT imaging system with a beam blocking grid in place is made using
      code based on EGSnrc, with the x-ray tube portion of the simulation including
      electron backscatter between the anode and cathode. The inclusion of the electron
      backscatter allowed a more complete model of the contamination signal to be
      estimated. The contamination signal consists of the off-focal radiation (OFR) and
      source component scatter (photon scatter in source components such as tube
      housing, filters, and collimators). The MC model was validated against
      measurements collected on a bench top imaging system with a grid in place. The MC
      model was used to simulate 11 different grid design configurations in addition to
      a case with no grid. For each design a simulated projection with and without a
      phantom in place was computed. The simulated projections were then used to
      estimate the scatter and contamination portion of the signal using the signal
      behind the grid septa. The estimated signals from the grid data were compared to
      the actual signals labeled during the MC simulation. RESULTS: Simulated results
      showed good agreeance with measured results with the importance of including
      electron backscatter resulting in off-focal radiation in the simulation being
      highlighted. When the source was free of contamination photons all grids
      performed with an error less than 8% when estimating just the scatter from the
      object. When the contamination photons were included in the simulation, the error
      in estimating both the scatter and contamination signal rose by a factor of 4 on
      average. In the case when both signals are present, increasing the grid
      thickness, changing the SGD, and reducing septa width and air interspace sizes
      all showed the ability to improve the grid-based estimates of the object scatter
      and contamination portion signal. CONCLUSIONS: The inclusion of the contamination
      signal in MC simulations of x-ray imaging systems is important in the design,
      validation, and evaluation of measurement-based scatter methods. Beam blocking
      grids show potential not only in object scatter estimation but in the estimation
      of the contamination signal, but appropriate interpolation functions must be used
      to account for higher frequencies found in contamination signal.

PMID- 29360152
TI  - Effect of Thermostable alpha-Amylase Addition on Producing the Porous-Structured
      Noodles Using Extrusion Treatment.
AB  - : Problems with rehydration and palatability are considered as unacceptable
      quality characteristics for the noodles produced using high-strength extrusion
      technique. Thus, the aim of this study was to solve these problems by designing a
      novel method to create a porous structure for the high-strength extruded noodles
      (HENs). The quality indices of HENs were significantly improved after adding to
      them thermostable alpha-amylase (TalphaA) at 0.05% to 0.10%. The microstructure
      graphs showed that a well-developed porous structures was successfully created
      throughout noodle strands. This indicated that the TalphaA has effectively worked
      on starch granules in spite of the high-strength performance of the extrusion
      process. MALLS-GFC, X-ray diffraction, and differential scanning calorimeter
      investigations showed that the appearance of a porous structure was mainly
      attributed to the internal collapse of alpha-1,4-glycosidic bonds and the
      dissolution of water-soluble degradation products, such as dextrin and
      oligosaccharides. Moreover, the slight inhibited effect of excess TalphaA on the
      starch gelatinization was because of the fact that the high enzyme concentration
      might cause TalphaA to adhere or overlay on it. PRACTICAL APPLICATION: The
      rehydration and palatability properties of HENs were greatly improved by creating
      a well-developed or honeycomb-like porous structure using TalphaA at low
      concentration. The findings of this study could be applied to enhance the quality
      characteristics of HENs and to encourage the research and development in the
      noodle industry.

PMID- 29360156
TI  - Erratum.

PMID- 29360157
TI  - Feasibility study of range-based registration using daily cone beam CT for
      intensity-modulated proton therapy.
AB  - PURPOSE: Proton dose coverage is sensitive to proton beam range. The current
      practice of CT number-based registration for patient positioning focuses on
      matching the target and is not sufficient for proton therapy because the proton
      range depends on the medium traversed by the beam. Patient body deformations and
      anatomical changes result in range deviation in the target. We propose proton
      range-based registration to minimize the range deviation. METHODS: The range was
      calculated from cone beam-computed tomography (CBCT) of the patient on couch, and
      the range deviation was the difference of the calculated range from that on the
      initial (day 1) CBCT. In the investigated prostate cases in which the main cause
      of range deviation was the rotation of femur bones, and in the investigated
      abdomen cases in which the main cause of range deviation was body growth and
      anatomic change, our range-based registration was used to obtain the optimal beam
      angle by minimizing the range deviation. The new angle was limited to be +/-5
      degrees  from that planned to prevent potentially increased dose to the organs at
      risk. To demonstrate the benefit of range-based registration, we investigated the
      range at the voxels on the surface of the target volume. The calculation error of
      range deviation due to CBCT scatter was investigated by using solid water
      phantoms with different thicknesses. Range-based registration using both CBCTs
      and CTs was performed in cases of two patients with pelvic rhabdomyosarcoma and
      one patient with upper abdominal tumor. The range was represented by the water
      equivalent thickness to shorten the computation for online application purposes.
      RESULTS: In the phantom study, the calculation error of range deviation due to
      CBCT scatter was within 2 mm for a 1-cm thickness change (the mean range
      deviation was 0.8 mm). In the CT study of the prostate cases, the range deviation
      (mean +/- root-mean-square deviation) on the contour in each slice was
      efficiently reduced from 3.6 +/- 2.8 mm to 2.1 +/- 1.4 mm, with most slices being
      within 3 mm; in the CT study of the abdomen cases, the range deviation of the
      whole set was reduced from 4.4 +/- 1.9 mm to 3.5 +/- 2.1 mm. Both the mean and
      root-mean-square deviation of the range deviation on each treatment day were
      decreased. The dose coverage on the target was improved and the dose on the OARs
      was only slightly changed. CONCLUSION: Range-based registration can efficiently
      mitigate range deviation due to patient positioning and anatomical changes. It
      can shorten patient positioning time and reduce the patient's dose from CBCT.

PMID- 29360158
TI  - Characteristics and Outcomes of Adult Inpatients With Malnutrition.
AB  - BACKGROUND: The diagnosis of malnutrition remains controversial. Furthermore, it
      is unknown if physician diagnosis of malnutrition impacts outcomes. We sought to
      compare outcomes of patients with physician diagnosed malnutrition to patients
      recognized as malnourished by registered dietitians (RDs), but not physicians,
      and to describe the impact of each of 6 criteria on the diagnosis of
      malnutrition. METHODS: We conducted a retrospective cohort study of adult
      patients identified as meeting criteria for malnutrition. Pediatric, psychiatric,
      maternity, and rehabilitation patients were excluded. Patient demographics,
      clinical data, malnutrition type and criteria, nutrition interventions, and
      outcomes were abstracted from the electronic medical record. RESULTS: RDs
      identified malnutrition for 291 admissions during our study period. This
      represents 4.1% of hospital discharges. Physicians only diagnosed malnutrition on
      93 (32%) of these cases. Physicians diagnosed malnutrition in 43% of patients
      with a body mass index <18.5 but only 26% of patients with body mass index higher
      than 18.5. Patients with a physician diagnosis had a longer length of stay (mean
      14.9 days vs 7.1 days) and were more likely to receive parenteral nutrition (PN)
      (20.4% vs 4.6%). Of the patients, 62% had malnutrition due to chronic illness. Of
      the 6 criteria used to identify malnourished patients, weight loss and reduced
      energy intake were the most common. CONCLUSIONS: Malnutrition is underrecognized
      by physicians. However, further research is needed to determine if physician
      recognition and treatment of malnutrition can improve outcomes. The most
      important criteria for identifying malnourished patients in our cohort were
      weight loss and reduced energy intake.

PMID- 29360159
TI  - Potent and selective pharmacodynamic synergy between the metabotropic glutamate
      receptor subtype 2-positive allosteric modulator JNJ-46356479 and levetiracetam
      in the mouse 6-Hz (44-mA) model.
AB  - OBJECTIVE: We previously demonstrated that positive allosteric modulators (PAMs)
      of metabotropic glutamate subtype 2 (mGlu2 ) receptors have potential synergistic
      interactions with the antiseizure drug levetiracetam (LEV). The present study
      utilizes isobolographic analysis to evaluate the combined administration of JNJ
      46356479, a selective and potent mGlu2 PAM, with LEV as well as sodium valproate
      (VPA) and lamotrigine (LTG). METHODS: The anticonvulsant efficacy of JNJ-46356479
      was evaluated in the 6-Hz model of psychomotor seizures in mice. JNJ-46356479 was
      administered in combination with LEV using 3 fixed dose-ratio treatment groups in
      the mouse 6-Hz (44-mA) seizure test. The combination of JNJ-46356479 with LEV was
      also evaluated in the mouse corneal kindling model. The potential interactions of
      JNJ-46356479 with the antiseizure drugs VPA and LTG were also evaluated using
      fixed dose-ratio combinations. Plasma levels were obtained for analysis of
      potential pharmacokinetic interactions for each combination studied in the mouse
      6-Hz model. RESULTS: JNJ-46356479 was active in the 6-Hz model at both 32-mA and
      44-mA stimulus intensities (median effective dose = 2.8 and 10.2 mg/kg,
      respectively). Using 1:1, 1:3, and 3:1 fixed dose-ratio combinations (LEV:JNJ
      46356479), coadministration was significantly more potent than predicted for
      additive effects, and plasma levels suggest this synergism was not due to
      pharmacokinetic interactions. Studies in kindled mice further demonstrate the
      positive pharmacodynamic interaction of LEV with JNJ-46356479. Using 1:1 dose
      ratio combinations of JNJ-46356479 with either VPA or LTG, there were no
      significant differences observed for coadministration. SIGNIFICANCE: These
      studies demonstrate a synergistic interaction of JNJ-46356479 with LEV, whereas
      no such effect occurred for JNJ-46356479 with either VPA or LTG. The synergy
      seems therefore to be specific to LEV, and the combination LEV/mGlu2 PAM has the
      potential to result in a rational polypharmacy approach to treat patients with
      refractory epilepsy, once it has been confirmed in clinical studies.

PMID- 29360160
TI  - Trends in multiple myeloma presentation, management, cost of care, and outcomes
      in the Medicare population: A comprehensive look at racial disparities.
AB  - BACKGROUND: Outcomes have improved significantly in multiple myeloma (MM), but
      racial disparities in health care access and survival exist. A comprehensive
      analysis exploring MM care and racial disparities is warranted. METHODS: Patients
      with MM from 1991 to 2010 in the Surveillance, Epidemiology, and End Results
      Medicare database were evaluated for racial trends in clinical myeloma-defining
      events (MDEs), the receipt of treatment (drugs and stem cell transplantation;
      [SCT]), the cost of care, and overall survival (OS). RESULTS: Among 35,842
      patients, the frequency of all MDEs at diagnosis increased over time; whereas, in
      recent years (2006-2010), all MDEs with the exception of renal dialysis
      decreased. Blacks had highest rates for all MDEs except bone fractures, which
      were highest in whites. Over time, the proportion of patients who received any
      treatment, multiple agents, and SCT increased significantly, and the largest
      increase was observed in the receipt of immunomodulatory drugs and steroids.
      There was greater receipt of bortezomib and SCT among whites and blacks and
      higher receipt of immunomodulatory drugs among Hispanics and Asians (P < .001).
      Medicare claims were highest during first 6 months after MM diagnosis for blacks
      and at any time after MM diagnosis for Hispanics. Over time, Medicare claims
      increased most steadily for Hispanics (P < .001). Hypercalcemia, renal
      dysfunction, and bone fractures were associated with inferior OS. Blacks and
      Asians had superior OS compared with whites, but racial differences in OS became
      less pronounced during 2006 through 2010 (P = .182) compared with prior years (P
      < .01). Better OS was noted among patients who had higher median incomes.
      CONCLUSIONS: The current results indicate that there have been significant
      changes in the management of patients with MM over time and provide an in-depth
      understanding of the factors that may help explain racial disparities. Cancer
      2018;124:1710-21. (c) 2018 American Cancer Society.

PMID- 29360161
TI  - Germline mutation prevalence in individuals with pancreatic cancer and a history
      of previous malignancy.
AB  - BACKGROUND: Approximately 10% of pancreatic adenocarcinoma (PC) cases are
      attributed to hereditary causes. Individuals with PC and a personal history of
      another cancer associated with hereditary breast and ovarian cancer (HBOC) or
      Lynch syndrome (LS) may be more likely to carry germline mutations. METHODS:
      Participants with PC and a history of cancer were selected from a pancreatic
      disease registry. Of 1296 individuals with PC, 149 had a relevant history of
      cancer. If banked DNA was available, a multigene panel was performed for
      individuals who had not 1) previously had a mutation identified through clinical
      testing or 2) undergone clinical multigene panel testing with no mutations
      detected. RESULTS: Twenty-two of 124 individuals with PC and another HBOC- or LS
      related cancer who underwent genetic testing had a mutation identified in a PC
      susceptibility gene (18%). If prostate cancer is excluded, the mutation
      prevalence increased to 23% (21/93). Mutation carriers were more likely to have
      more than 1 previous cancer diagnosis (P = .001), to have had clinical genetic
      testing (P = .001), and to meet National Comprehensive Cancer Network (NCCN)
      genetic testing criteria (P < .001). Approximately 23% of mutation carriers did
      not meet NCCN HBOC or LS testing guidelines based on their personal cancer
      history and reported cancer history in first-degree relatives. CONCLUSION: At
      least 18% of individuals with PC and a personal history of other HBOC- or LS
      related cancers carry mutations in a PC susceptibility gene based on our data,
      suggesting that criteria for genetic testing in individuals with PC should
      include consideration of previous cancer history. Cancer 2018;124:1691-700. (c)
      2018 American Cancer Society.

PMID- 29360162
TI  - Bone marrow versus mobilized peripheral blood stem cells in haploidentical
      transplants using posttransplantation cyclophosphamide.
AB  - BACKGROUND: Incidence of graft-versus-host disease (GVHD) in haploidentical bone
      marrow (BM) transplants using posttransplantion cyclophosphamide (PT-Cy) is low,
      whereas GVHD using mobilized peripheral blood stem cells (PBSC) ranges between
      30% and 40%. METHODS: To evaluate the effect of stem cell source in
      haploidentical transplantation with PT-Cy, we analyzed 451 patients transplanted
      for acute myeloid leukemia or acute lymphoblastic leukemia reported to the
      European Society for Blood and Marrow Transplantation. RESULTS: BM was used in
      260 patients, and PBSC were used in 191 patients. The median follow-up was 21
      months. Engraftment was lower in BM (92% vs 95%, P < 0.001). BM was associated
      with a lower incidence of stage II-IV and stage III-IV acute GVHD (21% vs 38%, P
      <= .01; and 4% vs 14%, P < .01, respectively). No difference in chronic GVHD,
      relapse, or nonrelapse mortality were found for PBSC or BM. The 2-year overall
      survival (OS) was 55% versus 56% (P = .57) and leukemia-free survival (LFS) was
      49% versus 54% (P = .74) for BM and PBSC, respectively. On multivariate analysis,
      PBSC were associated with an increased risk of stage II-IV (hazard ratio [HR],
      2.1; P < .001) and stage III-IV acute GVHD (HR, 3.8; P < .001). For LFS and OS,
      reduced intensity conditioning was the only factor associated with treatment
      failure (LFS: HR, 1.40; P = .04) and relapse (HR, 1.62; P = .02). CONCLUSION: In
      patients with acute leukemia in first or second remission receiving
      haploidentical transplantation with PT-Cy, the use of PBSC increases the risk of
      acute GVHD, whereas survival outcomes are comparable. Cancer 2018;124:1428-37.
      (c) 2018 American Cancer Society.

PMID- 29360163
TI  - Inflammation and Trajectory of Renal Function in Community-Dwelling Older Adults.
AB  - OBJECTIVES: To examine the hypothesis that the inflammatory state of aging is a
      risk factor for accelerated renal function (RF) decline using inflammatory
      biomarkers and RF measures collected over 9 years of follow-up in relatively
      healthy individuals enrolled in the Invecchiare in Chianti study. DESIGN:
      Longitudinal. SETTING: Community. PARTICIPANTS: Individuals aged 60 and older
      with baseline estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73
      m2 and greater and no diabetes mellitus (DM) (N = 687). MEASURES: eGFR, as a
      proxy for RF, was determined using the Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equation at baseline and 3-, 6-, and 9-year follow-up.
      Incident chronic kidney disease (CKD) was defined as new-onset eGFR less than 60
      mL/min per 1.73 m2 at each follow-up. Predictors included baseline and time
      dependent inflammatory biomarkers: soluble tumor necrosis factor alpha receptors
      (sTNFalpha-R1 and -R2), interleukin (IL)-6, IL-18, IL-1beta, IL-1 receptor
      antagonist, and high-sensitivity C-reactive protein. RESULTS: Higher baseline
      sTNFalpha-R1 was significantly associated with lower eGFR over 9 years,
      independent of DM or blood pressure (baseline: beta^ = -0.39, P = .001; 3-year:
      beta^ = -0.26, P = .001; 6-year: beta^ = -0.36, P = .001; 9-year: beta^ = -0.47,
      P = .001). The rate of TNFalpha-R1 change was significantly associated with rate
      of eGFR change (beta^ = -0.18, P = .001). Baseline sTNFalpha-R1 predicted
      incident CKD (per 1-standard deviation increment: 3-year: relative risk (RR) =
      1.3, 95% confidence interval (CI) = 1.1-1.5; 6-year: RR = 1.5, 95% CI = 1.1-2.2;
      9-year RR = 1.6, 95% CI = 1.1-2.2). Similar results were found for sTNFalpha-R2.
      CONCLUSION: Baseline TNFalpha-R levels and their rates of change were
      significantly associated with RF decline and incident CKD in older adults
      independent of DM or blood pressure.

PMID- 29360164
TI  - Erratum.

PMID- 29360165
TI  - Erratum.

PMID- 29360166
TI  - Erratum.

PMID- 29360169
TI  - Adrenomedullin surges are linked to acute episodes of the systemic capillary leak
      syndrome (Clarkson disease).
AB  - BACKGROUND: Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and life
      threatening vascular disorder of unknown etiology. SCLS is characterized by
      abrupt and transient episodes of hypotensive shock and edema due to plasma
      leakage into peripheral tissues. The disorder has garnered attention recently
      because its initial presentation resembles more common vascular disorders
      including systemic anaphylaxis, sepsis, and acute infections with the
      Ebola/Marburg family of filoviruses. Although approximately 70-85% of patients
      with SCLS have a concurrent monoclonal gammopathy of unknown significance (MGUS),
      any contribution of the paraprotein to acute flares is unknown. PROCEDURE: To
      identify circulating factors that might trigger acute SCLS crises, we profiled
      transcriptomes of paired peripheral blood mononuclear cell fractions obtained
      from patients during acute attacks and convalescent intervals by microarray.
      RESULTS: This study uncovered 61 genes that were significantly up- or
      downregulated more than 2.5-fold in acute samples relative to respective
      baselines. One of the most upregulated genes was ADM, which encodes the
      vasoactive peptide adrenomedullin. A stable ADM protein surrogate (pro-ADM) was
      markedly elevated in SCLS acute sera compared to remission samples or sera from
      healthy controls. Monocytes and endothelial cells (ECs) from SCLS subjects
      expressed significantly more ADM in response to proinflammatory stimuli compared
      to healthy control cells. Application of ADM to ECs elicited protective effects
      on vascular barrier function, suggesting a feedback protective mechanism in SCLS.
      CONCLUSIONS: Since ADM has established hypotensive effects, differentiating
      between these dual actions of ADM is crucial for therapeutic applications aimed
      at more common diseases associated with increased ADM levels.

PMID- 29360170
TI  - A mendelian form of neural tube defect caused by a de novo null variant in
      SMARCC1 in an identical twin.
AB  - Neural tube defects (NTDs) are among the most common birth defects in humans and
      yet their molecular etiology remains poorly understood. NTDs are believed to
      result from the complex interaction of environmental factors with a multitude of
      genetic risk factors in a classical multifactorial disease model. Mendelian forms
      of NTDs in which single variants are sufficient to cause the disease are
      extremely rare. We report a monozygotic twin with severe NTDs (occipital
      encephalocele and myelomeningocele) and a shared de novo, likely truncating,
      variant in SMARCC1. RTPCR analysis suggests the potential null nature of the
      variant attributed to nonsense-mediated decay. SMARCC1 is extremely constrained
      in humans and encodes a highly conserved core chromatin remodeler, BAF155. Mice
      that are heterozygous for a null allele or homozygous for a hypomorphic allele
      develop severe NTDs in the form of exencephaly. This is the first report of
      SMARCC1 mutation in humans, and it shows a critical and conserved requirement for
      intact BAF chromatin remodeling complex in neurulation. Ann Neurol 2018;83:433
      436.

PMID- 29360168
TI  - Activity-dependent plasticity of presynaptic GABAB receptors at parallel fiber
      synapses.
AB  - Parallel fiber synapses in the cerebellum express a wide range of presynaptic
      receptors. However, presynaptic receptor expression at individual parallel fiber
      synapses is quite heterogeneous, suggesting physiological mechanisms regulate
      presynaptic receptor expression. We investigated changes in presynaptic GABAB
      receptors at parallel fiber-stellate cell synapses in acute cerebellar slices
      from juvenile mice. GABAB receptor-mediated inhibition of excitatory postsynaptic
      currents (EPSCs) is remarkably diverse at these synapses, with transmitter
      release at some synapses inhibited by >50% and little or no inhibition at others.
      GABAB receptor-mediated inhibition was significantly reduced following 4 Hz
      parallel fiber stimulation but not after stimulation at other frequencies. The
      reduction in GABAB receptor-mediated inhibition was replicated by bath
      application of forskolin and blocked by application of a PKA inhibitor,
      suggesting activation of adenylyl cyclase and PKA are required. Immunolabeling
      for an extracellular domain of the GABAB2 subunit revealed reduced surface
      expression in the molecular layer after exposure to forskolin. GABAB receptor
      mediated inhibition of action potential evoked calcium transients in parallel
      fiber varicosities was also reduced following bath application of forskolin,
      confirming presynaptic receptors are responsible for the reduced EPSC inhibition.
      These data demonstrate that presynaptic GABAB receptor expression can be a
      plastic property of synapses, which may compliment other forms of synaptic
      plasticity. This opens the door to novel forms of receptor plasticity previously
      confined primarily to postsynaptic receptors.

PMID- 29360171
TI  - New perspectives in epilepsy neuropathology.

PMID- 29360175
TI  - Addendum.

PMID- 29360173
TI  - What are the origins and relevance of spontaneous bladder contractions? ICI-RS
      2017.
AB  - INTRODUCTION: Storage phase bladder activity is a counter-intuitive observation
      of spontaneous contractions. They are potentially an intrinsic feature of the
      smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as
      well as other muscular elements in the mucosa may substantially influence them.
      They are identified in several models explaining lower urinary tract dysfunction.
      METHODS: A consensus meeting at the International Consultation on Incontinence
      Research Society (ICI-RS) 2017 congress considered the origins and relevance of
      spontaneous bladder contractions by debating which cell type(s) modulate bladder
      spontaneous activity, whether the methodologies are sufficiently robust, and
      implications for healthy and abnormal lower urinary tract function. RESULTS: The
      identified research priorities reflect a wide range of unknown aspects. Cellular
      contributions to spontaneous contractions in detrusor smooth muscle are still
      uncertain. Accordingly, insight into the cellular physiology of the bladder wall,
      particularly smooth muscle cells, interstitial cells, and urothelium, remains
      important. Upstream influences, such as innervation, endocrine, and paracrine
      factors, are particularly important. The cellular interactions represent the key
      understanding to derive the integrative physiology of organ function, notably the
      nature of signalling between mucosa and detrusor layers. Indeed, it is still not
      clear to what extent spontaneous contractions generated in isolated preparations
      mirror their normal and pathological counterparts in the intact bladder. Improved
      models of how spontaneous contractions influence pressure generation and sensory
      nerve function are also needed. CONCLUSIONS: Deriving approaches to robust
      evaluation of spontaneous contractions and their influences for experimental and
      clinical use could yield considerable progress in functional urology.

PMID- 29360176
TI  - Advancements of the sFIDA method for oligomer-based diagnostics of
      neurodegenerative diseases.
AB  - Early diagnosis of Alzheimer's disease (AD) is of great importance for the
      development of therapeutics and their application in the clinical environment.
      Amyloid beta (Abeta) oligomers are crucial for the onset and progression of AD
      and represent a popular drug target, being presumably the most direct biomarker.
      Efforts to measure Abeta oligomers in body fluids are hampered by the low analyte
      concentration and presence of Abeta monomers. The surface-based fluorescence
      intensity distribution analysis (sFIDA) features both highly specific and
      sensitive oligomer quantitation as well as total insensitivity towards monomers.
      In this Review, we highlight structural features of oligomeric and fibrillar
      Abeta. Recent advancements in sFIDA assay development have been the successful
      automation, adaption for additional biomarkers such as alpha-synuclein oligomers,
      and significant improvement of essential assay parameters.

PMID- 29360177
TI  - Low plasma protein Z levels are associated with an increased risk for
      perioperative bleedings.
AB  - BACKGROUND AND OBJECTIVES: Protein Z (PZ) deficiency has been implicated both in
      bleeding diatheses and in thrombophilia. Considering its ambiguous nature and the
      conflicting clinical data so far, we set out to evaluate the impact of low PZ on
      perioperative bleeding in patients who underwent surgical (ENT) interventions
      involving a high risk of bleeding. PATIENTS AND METHODS: After exclusion of other
      coagulation disorders, 154 Patients were stratified into quartiles according to
      PZ plasma concentrations to evaluate the relation between PZ and bleeding
      complications. RESULTS: Low PZ levels were associated with increased blood loss
      (P < .001), increased need for blood transfusions (P < .001), and a higher rate
      of surgical revisions (P = .009) in a concentration-dependent fashion. Low PZ
      caused earlier (within 24 hours) and repetitive bleedings (P = .005). The number
      of major bleeding episodes was significantly increased when low PZ was combined
      with bleeding history (P < .05). Finally, ROC analyses confirmed the predictive
      value of low PZ for bleeding complications and PZ-thresholds for clinical
      practice were determined. CONCLUSIONS: Low PZ appears to be an underestimated
      risk factor for perioperative bleeding. Determination of PZ plasma concentrations
      might be useful in the preoperative workup in patients with a bleeding history,
      when detailed clotting analyses remain inconclusive.

PMID- 29360178
TI  - Electronic Rearrangement in Molecular Plasmons: An Electron Density and
      Electrostatic Potential-Based Study.
AB  - Plasmonic modes in single-molecule systems have been previously identified by
      scaling two-electron interactions in calculating excitation energies. Analysis of
      transition dipole moments for states of polyacenes based on configuration
      interaction is another method for characterising molecular plasmons. The
      principal features in the electronic absorption spectra of polyacenes are a low
      intensity, lower-in-energy peak and a high-intensity, higher-in-energy peak. From
      calculations using time-dependent density functional theory with the B3LYP/cc
      pVTZ basis set, both these peaks are found to result from the same set of
      electronic transitions, that is, HOMO-n to LUMO and HOMO to LUMO+n, where n
      varies as the number of fused rings increases. In this work, the excited states
      of polyacenes, naphthalene through pentacene, are analysed using electron
      densities and molecular electrostatic potential (MESP) topography. Compared to
      other excited states the bright and dark plasmonic states involve the least
      electron rearrangement. Quantitatively, the MESP topography indicates that the
      variance in MESP values and the displacement in MESP minima positions, calculated
      with respect to the ground state, are lowest for plasmonic states. The excited
      state electronic density profiles and electrostatic potential topographies
      suggest the least electron rearrangement for the plasmonic states. Conversely,
      high electron rearrangement characterises a single-particle excitation. The
      molecular plasmon can be called an excited state most similar to the ground state
      in terms of one-electron properties. This is found to be true for silver (Ag6 )
      and sodium (Na8 ) linear chains as well.

PMID- 29360179
TI  - Hitchhiking in space: Ancestry in adapting, spatially extended populations.
AB  - Selective sweeps reduce neutral genetic diversity. In sexual populations, this
      "hitchhiking" effect is thought to be limited to the local genomic region of the
      sweeping allele. While this is true in panmictic populations, we find that in
      spatially extended populations the combined effects of many unlinked sweeps can
      affect patterns of ancestry (and therefore neutral genetic diversity) across the
      whole genome. Even low rates of sweeps can be enough to skew the spatial
      locations of ancestors such that neutral mutations that occur in an individual
      living outside a small region in the center of the range have virtually no chance
      of fixing in the population. The fact that nearly all ancestry rapidly traces
      back to a small spatial region also means that relatedness between individuals
      falls off very slowly as a function of the spatial distance between them.

PMID- 29360180
TI  - The enduring effect of laser iridoplasty.

PMID- 29360181
TI  - The hidden work of a journal editor.

PMID- 29360182
TI  - Research in Nursing & Health Author Guidelines.

PMID- 29360183
TI  - Care coordination: Identifying and connecting the most appropriate care to the
      patients.
AB  - Although nurses are increasingly expected to fulfill the role of care
      coordinator, the knowledge and skills required to be an effective care
      coordinator are not well understood. The purpose of this study was to describe
      the knowledge and skills required in care coordination practice using an
      interpretive phenomenological approach. Fifteen care coordinators from 10
      programs were interviewed over a 6-month period. Semi-structured face-to-face
      interviews were audio recorded, transcribed, and analyzed using interpretive
      phenomenology. The central theme of care coordination practice was bridging the
      patient and the healthcare systems. To bridge, care coordinators needed to have
      knowledge of the patient and healthcare system as well as the skills to identify
      and negotiate treatments appropriate for the patient. The most salient finding
      and new to this literature was that care coordinators who used their medical
      knowledge about available treatment options to discern and negotiate for the most
      appropriate care to the patient made differences in patient outcomes. Nurses with
      medical and healthcare system knowledge, combined with the skills to navigate and
      negotiate with others in an increasingly complex healthcare system, are well
      situated to be care coordinators and generate optimal outcomes. Further
      investigations of critical care coordinator competencies are needed to support
      nurses currently enacting the role of care coordinator and to prepare future
      nurses to fulfill the role.

PMID- 29360184
TI  - Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in
      adults after related, unrelated, and haploidentical transplantations.
AB  - INTRODUCTION: Although a number of studies were published on the efficacy of post
      transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD)
      prophylaxis, no large studies prospectively evaluated this strategy in related,
      unrelated, and haploidentical grafts. METHODS: In this study, GVHD prophylaxis
      for 57 matched bone marrow (MBM) grafts consisted of single-agent PTCy, for 88
      matched PBSC grafts (MPBSC) consisted of PTCy, tacrolimus, and mycophenolate
      mofetil (MMF) 30 mg/kg, and for 55 mismatched grafts (MMGs) consisted of PTCy,
      tacrolimus and MMF 45 mg/kg. RESULTS: The study met the primary endpoint to
      demonstrate equivalent rates of acute GVHD grade II-IV (11%, 17%,19%, P = .46),
      III-IV (7%, 2%, 6%, P = .41), and moderate and severe chronic GVHD (22%, 11%,
      15%, P = .23). There was also no differences in non-relapse mortality (11% vs 15%
      vs 17%, P = .75), overall survival (63% vs 71% vs 56%, P = .72), event-free
      survival (51% vs 66% vs 48%, P = .32) for MBM, MPBSC, and MMG groups,
      respectively. Toxicity was comparable between groups except higher incidence of
      nephrotoxicity in combination arms (P = .0005) and higher incidence of graft
      failures in MMG group (P = .004). CONCLUSION: The suggested risk-adapted PTCy
      based prophylaxis is feasible and is associated with low GVHD incidence and
      mortality in all types of grafts. The study was registered on clinicaltrials.gov
      (NCT02294552).

PMID- 29360185
TI  - Quantifying the effect of light activated outer and inner retinal inhibitory
      pathways on glutamate release from mixed bipolar cells.
AB  - Inhibition mediated by horizontal and amacrine cells in the outer and inner
      retina, respectively, are fundamental components of visual processing. Here, our
      purpose was to determine how these different inhibitory processes affect
      glutamate release from ON bipolar cells when the retina is stimulated with full
      field light of various intensities. Light-evoked membrane potential changes
      (DeltaVm ) were recorded directly from axon terminals of intact bipolar cells
      receiving mixed rod and cone inputs (Mbs) in slices of dark-adapted goldfish
      retina. Inner and outer retinal inhibition to Mbs was blocked with bath applied
      picrotoxin (PTX) and NBQX, respectively. Then, control and pharmacologically
      modified light responses were injected into axotomized Mb terminals as command
      potentials to induce voltage-gated Ca2+ influx (QCa ) and consequent glutamate
      release. Stimulus-evoked glutamate release was quantified by the increase in
      membrane capacitance (DeltaCm ). Increasing depolarization of Mb terminals upon
      removal of inner and outer retinal inhibition enhanced the DeltaVm /QCa ratio
      equally at a given light intensity and inhibition did not alter the overall
      relation between QCa and DeltaCm . However, relative to control, light responses
      recorded in the presence of PTX and PTX + NBQX increased DeltaCm unevenly across
      different stimulus intensities: at dim stimulus intensities predominantly the
      inner retinal GABAergic inhibition controlled release from Mbs, whereas the inner
      and outer retinal inhibition affected release equally in response to bright
      stimuli. Furthermore, our results suggest that non-linear relationship between
      QCa and glutamate release can influence the efficacy of inner and outer retinal
      inhibitory pathways to mediate Mb output at different light intensities.

PMID- 29360187
TI  - Altered proportion of CCR2+ and CX3CR1+ circulating monocytes in neovascular age
      related macular degeneration and polypoidal choroidal vasculopathy.
AB  - BACKGROUND: We investigated the expression of chemokine receptors CCR2 (C-C
      chemokine receptor) 2 and CX3CR1 (C-X3-C receptor 1) on circulating monocyte
      subsets in patients with neovascular age-related macular degeneration (AMD) and
      patients with polypoidal choroidal vasculopathy (PCV). METHODS: We recruited
      patients with neovascular AMD, patients with PCV and age-matched healthy controls
      for this prospective case-control study. All participants underwent comprehensive
      clinical examination and imaging. Freshly sampled venous blood was prepared for
      flow cytometry, where we determined the proportion of CCR2+ - and CX3CR1+ 
      positive cells in monocyte subsets identified using monocyte identification and
      subgrouping surface markers CD14, CD16 and HLA-DR. RESULTS: Patients with
      neovascular AMD had significantly increased proportion of CCR2+ and CX3CR1+ non
      classical monocytes. PCV type 1 was associated with significantly increased CCR2+
      and CX3CR1+ in all monocyte subsets when compared to PCV type 2. CONCLUSIONS:
      Neovascular AMD is associated with increased expression of angiogenesis
      associated chemokine receptors in the pro-inflammatory non-classical monocytes.
      PCV differs from neovascular AMD immunologically and show immunological
      heterogeneity across angiographic subtypes.

PMID- 29360188
TI  - Paracentral acute middle maculopathy associated with severe vision loss following
      vitrectomy for vitreous haemorrhage.

PMID- 29360189
TI  - Development of an overactive bladder assessment tool (BAT): A potential
      improvement to the standard bladder diary.
AB  - AIMS: To develop a comprehensive patient-reported bladder assessment tool (BAT)
      for assessing overactive bladder (OAB) symptoms, bother, impacts, and
      satisfaction with treatment. METHODS: Subjects were consented and eligibility was
      confirmed by a recruiting physician; subjects were then scheduled for in-person
      interviews. For concept elicitation and cognitive interviews, 30 and 20 subjects,
      respectively, were targeted for recruitment from US sites. All interviews were
      conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and
      analyzed using a qualitative data analysis software program. A draft BAT was
      created based on the results of the concept elicitation interviews and further
      revised based on cognitive interviews as well as feedback from an advisory board
      of clinical and patient-reported outcome (PRO) experts. RESULTS: Nocturia,
      daytime frequency, and urgency were reported by all subjects (n = 30, 100.0%),
      and incontinence was reported by most subjects (n = 25, 83.3%). The most
      frequently reported impacts were waking up to urinate (n = 30, 100.0%),
      embarrassment/shame (n = 24, 80.0%), stress/anxiety (n = 23, 76.7%), and lack of
      control (n = 23, 76.7%). Following analysis, item generation, cognitive
      interviews, and advisory board feedback, the resulting BAT contains four
      hypothesized domains (symptom frequency, symptom bother, impacts, and
      satisfaction with treatment) and 17 items with a 7-day recall period.
      CONCLUSIONS: The BAT has been developed in multiple stages with input from both
      OAB patients and clinical experts following the recommended processes included in
      the FDA PRO Guidance for Industry. Once fully validated, we believe it will offer
      a superior alternative to use of the bladder diary and other PROs for monitoring
      OAB patients in clinical trials and clinical practice.

PMID- 29360190
TI  - When words matter: A "suspicious" urinary tract cytology diagnosis improves
      patient follow-up among nonurologists.
AB  - BACKGROUND: Urinary tract cytology (UTC) specimens diagnosed using high-risk
      indeterminate categories such as "atypical urothelial cells, cannot exclude high
      grade urothelial carcinoma" (AUC-H) or "suspicious for high-grade urothelial
      carcinoma" (SHGUC) have a high rate of detection of high-grade urothelial
      carcinoma on subsequent biopsy. Although urologists are familiar with such
      terminology, it is unclear whether patients receive appropriate follow-up when
      UTC is ordered by nonurologists. In the current study, the authors investigated
      whether the use of AUC-H versus SHGUC altered patient management among
      nonurologists. METHODS: Specimens signed out as AUC-H or SHGUC were identified
      from the archives of the study institution, which included periods of time before
      the use of the standardized Johns Hopkins Hospital template, during use of the
      Johns Hopkins Hospital template, and after institution of The Paris System for
      Reporting Urinary Cytology. RESULTS: Approximately one-half of the specimens
      diagnosed as AUC-H were not investigated further when ordered by nonurologists.
      Patients with specimens diagnosed as AUC-H received fewer subsequent biopsies
      (14% vs 53%; P < .001) when the specimens were ordered by nonurologists versus
      urologists, despite having similar rates of high-grade urothelial carcinoma on
      follow-up biopsy (67% vs 66%). When specimens ordered by nonurologists were
      diagnosed as SHGUC, these patients received more follow-up (100%) compared with
      those whose specimens were diagnosed as AUC-H (44%; P < .001). Patients with
      specimens ordered by nonurologists also received more follow-up biopsies when
      these were diagnosed as suspicious (60%) compared with patients whose specimens
      were diagnosed as AUC-H (14%; P < .001). CONCLUSIONS: Use of the word
      "suspicious" for the high-risk indeterminate category results in greater follow
      up among nonurologists ordering UTC specimens. Cancer Cytopathol 2018;126:282-8.
      (c) 2018 American Cancer Society.

PMID- 29360191
TI  - Insulinoma-associated protein 1 is a sensitive and specific marker of
      neuroendocrine lung neoplasms in cytology specimens.
AB  - BACKGROUND: Recent studies suggest that insulinoma-associated protein 1 (INSM1)
      is a sensitive and specific marker of neuroendocrine neoplasms. The aims of this
      study were to determine whether INSM1 can be reliably used in cytology (Cellient)
      cell blocks, to ascertain whether staining correlates with paired surgical
      pathology specimens, and to compare its sensitivity and specificity with those of
      synaptophysin (SYN), chromogranin (CHR), and CD56 for neuroendocrine lung tumors.
      METHODS: Seventy-four primary lung neoplasms diagnosed on cytology were stained
      with INSM1, SYN, CHR, and CD56: 41 small cell lung carcinomas (SCLCs), 1 large
      cell neuroendocrine carcinoma (LCNEC), 10 carcinoid tumors, 11 adenocarcinomas, 9
      squamous cell carcinomas, 1 mesothelioma and 1 poorly differentiated non-small
      cell lung carcinoma, not otherwise specified. In 20 cases, a paired surgical
      pathology specimen was also stained with INSM1. RESULTS: INSM1 was positive in 48
      of 52 primary lung neuroendocrine neoplasms (92%), including 38 of 41 SCLCs
      (93%), the only LCNEC (100%), and 9 of 10 carcinoid tumors (90%), and it was
      negative in all 22 non-neuroendocrine primary lung tumors. For SCLC, the
      sensitivity of INSM1 (93%) was lower than the sensitivity of CD56 (100%), equal
      to the sensitivity of SYN (93%), and higher than the sensitivity of CHR (35%).
      For carcinoid tumors, the sensitivity of INSM1 (90%) was lower than the
      sensitivity of all other markers (100% each). The specificity of INSM1 for
      neuroendocrine neoplasms as a group was 100%. INSM1 staining was concordant with
      surgical pathology specimens in all 20 paired cases. CONCLUSIONS: INSM1 can be
      used in cytopathology cell blocks, and it is sensitive and highly specific for
      neuroendocrine lung tumors. INSM1 staining in cytology cell blocks correlates
      well with surgical pathology specimens. Cancer Cytopathol 2018;126:243-52. (c)
      2018 American Cancer Society.

PMID- 29360192
TI  - Diagnostic criteria for disorders of arousal: A video-polysomnographic
      assessment.
AB  - OBJECTIVE: To assess video-polysomnographic (vPSG) criteria and their cutoff
      values for the diagnosis of disorders of arousal (DOAs; sleepwalking, sleep
      terror). METHODS: One hundred sixty adult patients with DOAs and 50 sex- and age
      matched healthy participants underwent a clinical evaluation and vPSG assessment
      to quantify slow wave sleep (SWS) interruptions (SWS fragmentation index,
      slow/mixed and fast arousal ratios, and indexes per hour) and the associated
      behaviors. First, a case-control analysis was performed in 100 patients and the
      50 controls to define the optimal cutoff values using receiver operating
      characteristic curves. Their sensitivity was then assessed in the other 60
      patients with DOAs. RESULTS: The SWS fragmentation index and the mixed, slow, and
      slow/mixed arousal indexes and ratios were higher in patients with DOAs than
      controls. The highest area under the curve (AUC) values were obtained for the SWS
      fragmentation and slow/mixed arousal indexes (AUC = 0.88 and 0.90, respectively).
      The SWS fragmentation index cutoff value of 6.8/h reached a sensitivity of 79%
      and a specificity of 82%. The slow/mixed arousal index had a sensitivity of 94%
      for the 2.5/h cutoff, and 100% specificity for 6/h. Both parameters showed good
      interrater agreement, and their sensitivities were confirmed in the second group
      of patients. Combining electroencephalographic parameters and video-based
      behavioral analyses increased the correct classification rate up to 91.3%.
      INTERPRETATION: Frequent slow/mixed arousals in SWS and complex behaviors during
      vPSG are strongly associated with DOAs, and could be promising biomarkers for the
      diagnosis of non-rapid eye movement parasomnias. Ann Neurol 2018;83:341-351.

PMID- 29360195
TI  - Reduction in late onset cytomegalovirus primary disease after discontinuation of
      antiviral prophylaxis in kidney transplant recipients treated with de novo
      everolimus.
AB  - BACKGROUND: Donor (D)+/recipient (R)- serostatus is closely associated with a
      higher risk of cytomegalovirus (CMV) infection and disease. Antiviral prophylaxis
      is conventionally used in such patients, but late onset CMV infection/disease
      still occurs after the discontinuation of prophylaxis. METHODS: We
      retrospectively analyzed the data of 215 low immunological risk patients who
      received kidney transplantation in our center between 2011 and 2016. RESULTS:
      Ninety-seven patients received a combination of everolimus (EVL)/reduced doses of
      calcineurin inhibitors (CNI) (EVL group) de novo, and 118 received a combination
      of mycophenolic acid (MPA)/standard doses of CNI (MPA group) de novo. All
      patients received induction by basiliximab, steroids, and standardized antiviral
      prophylaxis depending on their CMV D/R serostatus. D+/R- recipients comprised 17%
      (n = 16) of the EVL group and 19% (n = 22) of the MPA group (P = .722). In the
      D+/R- subgroup, the 1-year incidence of late onset CMV primary disease after the
      withdrawal of prophylaxis was lower in the EVL group than in the MPA group (6% vs
      41%, P = .025) while the rate of CMV disease in the D+/R+ group (8% vs 6%, P = 1)
      and the D-/R+ group (12% vs 9%, P = 1) were similar. Kaplan-Meier analysis of 1
      year CMV primary disease-free survival in seronegative patients was significantly
      better in the EVL group (P = .029, log-rank test). CONCLUSIONS: Our data suggest
      that de novo use of EVL may reduce late onset CMV primary disease after the
      withdrawal of antiviral prophylaxis in kidney transplantation patients.

PMID- 29360196
TI  - Expression of microRNAs in the ascites of patients with peritoneal carcinomatosis
      and peritonitis.
AB  - BACKGROUND: Peritoneal carcinomatosis (PCA) has a prognostic role in patients
      with gastrointestinal cancers. The differential diagnosis may be challenging due
      to the low sensitivity of cytology. Although microRNAs (miRNAs) have been a focus
      of various specimens and diseases, to the best of the authors' knowledge only
      limited knowledge exists regarding ascites. Herein, the authors systematically
      evaluated preanalytical factors and the potential of miRNAs as biomarkers of
      ascites. METHODS: The authors prospectively analyzed samples from patients with
      PCA, spontaneous bacterial peritonitis (SBP), and portal hypertension (no
      SBP/PCA). Various preanalytical factors such as extraction kits, sample storage,
      stability, and processing were systematically evaluated. MiRNA expression
      profiling using TaqMan Low Density Array and quantitative reverse transcriptase
      polymerase chain reaction were used to evaluate miRNA expression. RESULTS: All
      selected miRNAs were found to be reliably detectable in ascites samples. Ascites
      miRNAs were well preserved from degradation with required short-term and long
      term stability. MiRNA expression profiling in patients with PCA compared with
      those with no SBP/PCA revealed miR-21, miR-186, miR-222, and miR-483-5p to be
      upregulated and miR-26b to be downregulated. MiRNA expression validation analysis
      confirmed higher expression levels of miR-21 and miR-186 in patients with PCA
      compared with those with no SBP/PCA, whereas miR-223 was significantly
      upregulated in patients with SBP. A simple proportion score between miR-21 and
      miR-223 allowed the authors to discriminate between the patients with PCA and
      those with SBP with an area under the curve of 0.982 (95% confidence interval,
      0.943-1.022). CONCLUSIONS: The data from the current study provide novel evidence
      of the differential expression of miRNAs in ascites from patients with PCA and
      SBP, which may offer an additional miRNA-based molecular approach for the
      differential diagnosis of PCA. Cancer Cytopathol 2018;126:353-63. (c) 2018
      American Cancer Society.

PMID- 29360197
TI  - Clinical outcomes with distance-dominant multifocal and monofocal intraocular
      lenses in post-LASIK cataract surgery planned using an intraoperative
      aberrometer.
AB  - IMPORTANCE: Studies evaluating the clinical benefits of intraoperative
      aberrometry (IA) in cataract surgery are limited. BACKGROUND: The study was
      designed to determine whether IA improved clinical outcomes of post-laser in situ
      keratomileusis (LASIK) cataract surgery with different intraocular lenses (IOLs)
      implanted. DESIGN: A retrospective chart review of clinical outcomes from one
      surgeon at one surgical centre was conducted. It included post-LASIK cataract
      surgeries where IA was used for the confirmation of IOL power, with either a
      distant-dominant multifocal IOL or a monofocal IOL implanted. PARTICIPANTS:
      Records for 44 eyes of 31 patients were analysed. METHODS: Differences in visual
      acuity (VA) and refractions by lens type were compared, and the effects of IA
      were evaluated. MAIN OUTCOME MEASURES: Uncorrected distance VA and the percentage
      of eyes with a spherical equivalent refraction within 0.5D of the intended
      correction were the primary outcome measures. RESULTS: There was no statistically
      significant difference in the percentage of eyes with uncorrected distance VA of
      20/25 or better between IOL groups (P = 0.41). More eyes in the multifocal group
      had a refraction within 0.50D of intended (P = 0.03). In 39% of cases, the
      preoperative and IA power calculations suggested the same IOL power. When not
      equal, the IA results were not significantly more likely to be 'best' (P = 0.08).
      CONCLUSIONS AND RELEVANCE: Results suggest that a history of previous LASIK is
      not a contraindication to use of distant-dominant multifocal IOLs. IA did not
      appear to improve clinical outcomes in post-LASIK eyes, although a positive trend
      was evident.

PMID- 29360198
TI  - The risk of malignancy of atypical urothelial cells of undetermined significance
      in patients treated with chemohyperthermia or electromotive drug administration.
AB  - BACKGROUND: Chemohyperthermia (C-HT) or electromotive drug administration (EMDA)
      are alternative therapies to radical cystectomy in patients with non-muscle
      invasive bladder cancer who do not respond to intravesical therapy with bacille
      Calmette-Guerin. METHODS: The authors investigated a group of 87 patients with a
      diagnosis of high-grade non-muscle-invasive bladder carcinoma or carcinoma in
      situ. Of these, 45 patients received EMDA of mitomycin (EMDA/MMC) and 42 patients
      were treated with C-HT and mitomycin therapy (C-HT/MMC). In accordance with the
      Paris System for Reporting Urinary Cytology, a cytological diagnosis was made and
      patients with diagnoses of atypical urothelial cells (AUC), suspicious high-grade
      urothelial carcinoma (SHGUC), or high-grade urothelial carcinoma also underwent
      histological bladder biopsies. RESULTS: In accordance with the Paris System for
      Reporting Urinary Cytology, the AUC cases may have cytological features of SHGUC
      present on atypical degenerated cells. In analyzing the AUC group without the
      SHGUC cases diagnosed on the basis of degenerated urothelial cells, the authors
      found a significant association between the AUC category and a negative
      histological biopsy. The SHGUC group, including cases with a SHGUC diagnosis
      rendered on degenerated urothelial cells, was associated with high-grade
      urothelial carcinoma or carcinoma in situ (P =  .0269 for patients treated with
      EMDA/MMC and P =  .0049 for patients treated with C-HT/MMC). CONCLUSIONS: In the
      urine samples from patients treated with EMDA/MMC or C-HT/MMC, a diagnosis of
      SHGUC could be made even on degenerated urothelial cells when considering
      cellular degeneration as a "physiological" consequence of the treatment that
      involves either normal or neoplastic cells. Cancer Cytopathol 2018;126:200-6. (c)
      2018 American Cancer Society.

PMID- 29360199
TI  - Trimodal system for in vivo skin cancer screening with combined optical coherence
      tomography-Raman and colocalized optoacoustic measurements.
AB  - A new multimodal system for rapid, noninvasive in vivo skin cancer screening is
      presented, combining optical coherence tomography (OCT) and optoacoustic (OA)
      modalities to provide precise tumor depth determination with a Raman
      spectroscopic modality capable of detecting the lesion type and, thus, providing
      diagnostic capability. Both OA and Raman setups use wide field skin illumination
      to ensure the compliance with maximum permissible exposure (MPE) requirements.
      The Raman signal is collected via the OCT scanning lens to maximize the signal-to
      noise ratio of the measured signal while keeping radiation levels below MPE
      limits. OCT is used to optically determine the tumor thickness and for volumetric
      imaging whereas OA utilizes acoustic signals generated by optical absorption
      contrast for thickness determination at potentially higher penetration depths
      compared to OCT. Preliminary results of first clinical trials using our setup are
      presented. The measured lesion depth is in good agreement with histology results,
      while Raman measurements show distinctive differences between normal skin and
      melanocytic lesions, and, moreover, between different skin areas. In future, we
      will validate the setup presented for reliable detection of pathophysiological
      parameters, morphology and thickness of suspicious skin lesions.

PMID- 29360201
TI  - Erratum.

PMID- 29360203
TI  - Organizations and agencies launch efforts to improve research in adolescent and
      young adult cancers: Research and treatment in this unique population lags behind
      that in children and adults.

PMID- 29360202
TI  - Abdominal fat linked to cancer risk in postmenopausal women.

PMID- 29360200
TI  - Measurement properties of tools used to assess depression in adults with and
      without autism spectrum conditions: A systematic review.
AB  - : Depression is the most commonly experienced mental health condition in adults
      with autism spectrum conditions (ASC). However, it is unclear what tools are
      currently being used to assess depression in ASC, or whether tools need to be
      adapted for this group. This systematic review therefore aimed to identify tools
      used to assess depression in adults with and without ASC, and then evaluate these
      tools for their appropriateness and measurement properties. Medline, PsychINFO
      and Web of Knowledge were searched for studies of depression in: (a) adults with
      ASC, without co-morbid intellectual disability; and (b) adults from the general
      population without co-morbid conditions. Articles examining the measurement
      properties of these tools were then searched for using a methodological filter in
      PubMed, and the quality of the evidence was evaluated using the COSMIN checklist.
      Twelve articles were identified which utilized three tools to assess depression
      in adults with ASC, but only one article which assessed the measurement
      properties of one of these tools was identified and thus evaluated. Sixty-four
      articles were identified which utilized five tools to assess depression in
      general population adults, and fourteen articles had assessed the measurement
      properties of these tools. Overall, two tools were found to be robust in their
      measurement properties in the general population-the Beck Depression Inventory
      (BDI-II), and the patient health questionnaire (PHQ-9). Crucially only one study
      was identified from the COSMIN search, which showed weak evidence in support of
      the measurement properties of the BDI-II in an ASC sample. Implications for
      effective measurement of depression in ASC are discussed. Autism Res 2018, 11:
      738-754. (c) 2018 The Authors Autism Research published by International Society
      for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: Depression is the
      most common mental health problem experienced by adults with autism. However, the
      current study found very limited evidence regarding how useful tools developed
      for the general population are for adults with autism. We therefore suggest how
      these tools could be adapted to more effectively assess depression in adults with
      autism, and improve these individuals access to mental health assessment and
      support.

PMID- 29360204
TI  - Analysis evaluates how employers can help cancer survivors return to work.

PMID- 29360206
TI  - Erratum.

PMID- 29360207
TI  - Erratum.

PMID- 29360208
TI  - Progression of histopathological and behavioral abnormalities following mild
      traumatic brain injury in the male ferret.
AB  - White matter damage is an important consequence of traumatic brain injury (TBI)
      in humans. Unlike rodents, ferrets have a substantial amount of white matter and
      a gyrencephalic brain; therefore, they may represent an ideal small mammal model
      to study human-pertinent consequences of TBI. Here we report immunohistochemical
      and behavioral results after a controlled cortical impact (CCI) injury to the
      sensorimotor cortex of adult male ferrets. We assessed inflammation in the
      neocortex and white matter, and behavior at 1 day post injury and 1, 4, and 16
      weeks post injury (WPI). CCI in the ferret produced inflammation that originated
      in the neocortex near the site of the injury and progressed deep into the white
      matter with time. The density of microglia and astrocytes increased in the
      neocortex near the injury, peaking at 4WPI and remaining elevated at 16WPI.
      Microglial morphology in the neocortex was significantly altered in the first 4
      weeks, but showed a return toward normal at 16 weeks. Clusters of microglial
      cells in the white matter persisted until 16WPI. We assessed motor and cognitive
      behavior using the open field, novel object recognition, T-maze, and gait tests.
      A transient deficit in memory occurred at 4WPI, with a reduction of rearing and
      motor ability at 12 and 16WPI. Behavioral impairments coincide with features of
      the inflammatory changes in the neocortex revealed by immunohistochemistry. The
      ferret represents an important animal model to explore ongoing damage in the
      white matter and cerebral cortex after TBI.

PMID- 29360209
TI  - Erratum.

PMID- 29360210
TI  - Biosimilars: what the dermatologist should know.
AB  - Biosimilars are highly similar versions of approved branded biologics. In
      contrast to generics, which are identical copies of the originator medicines,
      biosimilars are considered unique but related molecules that differ from the
      originator reference product as well as from each other. Owing to the complexity
      of biologic medicines, such as therapeutic monoclonal antibodies, minor
      differences between biosimilars and the reference products are acceptable
      provided these differences do not result in any clinically meaningful differences
      in safety or efficacy. In addition, minor changes in structure and function may
      occur over time in originator biologic products as a result of alterations in
      production materials (e.g. cell lines), processes or conditions. The
      developmental process for biosimilars focuses on a 'totality of evidence'
      approach that emphasizes a stepwise investigational process, including
      comprehensive structural, functional, pharmacologic and clinical assessment for
      similarity. The goal of the phase 3 clinical development programme for a
      biosimilar is not to establish efficacy, per se, but to demonstrate that there
      are no clinically meaningful differences between the proposed biosimilar and the
      reference product. The requirement to show clinical similarity informs biosimilar
      study design, including the selection of the patient population, disease state
      (indication), study endpoints and statistical methods. Based on the clinical
      trial results in a representative patient population, results may be extrapolated
      to other indications provided scientific justification is demonstrated based on,
      among other things, similar mechanism of action in the extrapolated indications.
      This review presents the current state of knowledge with respect to biosimilars.
      We aim to provide the practising clinician with a working knowledge of
      biosimilars as well as provide some practical guidance on their use and potential
      benefits in treating dermatologic diseases.

PMID- 29360211
TI  - Emergency Department Patients With Acute Kidney Injury: Appropriately Discharged
      but Inadequately Followed-Up?

PMID- 29360213
TI  - Erratum.

PMID- 29360215
TI  - Incidence of retinal vein occlusion in open-angle glaucoma: a nationwide,
      population-based study using the Korean Health Insurance Review and Assessment
      Database.
AB  - IMPORTANCE: We determined the association between retinal vein occlusion (RVO)
      and open-angle glaucoma (OAG) in a Korean population by reviewing a dataset
      obtained from the Korean Health Insurance Review and Assessment (HIRA).
      BACKGROUND: To compare the RVO incidence for OAG patients with that for the
      general population in order to determine the association between RVO and OAG.
      DESIGN: Nationwide population-based retrospective study. PARTICIPANTS: HIRA data
      for 2011 through 2015. METHODS: The HIRA data for 2011 through 2015 was analysed
      in order to determine the incidence rates of RVO in the general population and in
      OAG patients. The standardized incidence ratios (SIRs) of RVO for OAG patients
      were determined with respect to the age- and gender-matched general population.
      MAIN OUTCOME MEASURES: SIRs of RVO. RESULTS: The RVO incidence rate for the
      general population during the 4-year study period (2012-2015) was 74.16 per 100
      000 person-years (95% confidence interval [CI], 73.79-74.54). A total of 272 143
      OAG patients were identified in 2011 as the population at risk. The RVO incidence
      rate for the OAG patients was 528.95 per 100 000 person-years (95% CI, 515.46
      542.79). The expected incidences of RVO in the OAG patients were 1760.66 during
      the 4-year study period. On the other hand, the observed incidences of RVO were
      5758. The SIR of RVO for OAG patients in reference to the general population was
      3.27 (95% CI, 3.19-3.35). CONCLUSIONS AND RELEVANCE: The RVO incidence rate for
      OAG patients is significantly higher than that for the general population.

PMID- 29360216
TI  - At the crossway of ER-stress and proinflammatory responses.
AB  - Immune cells detect specific microbes or damage to tissue integrity in order to
      initiate efficient immune responses. Abnormal accumulation of proteins in the
      endoplasmic reticulum (ER) can be seen as a sign of cellular malfunction and
      stress that triggers a collection of conserved emergency rescue programs. These
      different signaling cascades, which favor ER proteostasis and promote cell
      survival, are collectively known as the unfolded protein response (UPR). In
      recent years, a synergy between the UPR and inflammatory cytokine production has
      been unraveled, with different branches of the UPR entering in a cross-talk with
      specialized microbe sensing pathways, which turns on or amplify inflammatory
      cytokines production. Complementary to this synergetic activity, UPR induction
      alone, can itself be seen as a danger signal, and triggers directly or indirectly
      inflammation in different cellular and pathological models, this independently of
      the presence of pathogens. Here, we discuss recent advances on the nature of
      these cross-talks and how innate immunity, metabolism dysregulation, and ER
      signaling pathways intersect in specialized immune cells, such as dendritic cells
      (DCs), and contribute to the pathogenesis of inflammatory diseases.

PMID- 29360217
TI  - Rhodium(I)-Catalyzed Carboacylation/Aromatization Cascade Initiated by
      Regioselective C-C Activation of Benzocyclobutenones.
AB  - Described here is the first example of a rhodium-catalyzed
      carboacylation/aromatization cascade of a C=O bond by C-C activation. In this
      transformation, a reactive rhodaindanone complex is regioselectively generated
      and adds across a C=O bond with subsequent elimination, thus providing a unique
      strategy to access a multisubstituted benzofuran scaffold. A diverse range of
      benzofuran analogues were obtained in good yields. Mechanistic studies show a
      tricyclic lactone was a viable intermediate. Application of this methodology to
      the total synthesis of C13-deOH-viniferifuran and C13-deOH-diptoindonesin G was
      achieved.

PMID- 29360218
TI  - Methylparaben induces malformations and alterations on apoptosis, oxidant
      antioxidant status, ccnd1 and myca expressions in zebrafish embryos.
AB  - Methylparabens (MP) are widely used as preservatives in cosmetics, pharmacy, and
      food industry. Although acute toxicity studies in animals indicated that parabens
      are not significantly toxic, the effects of chronic exposure under sublethal
      doses are still unknown and the number of related studies is limited. Our aim was
      to evaluate the effects of MP on the development of zebrafish embryos focusing on
      development, locomotor activity, oxidant-antioxidant status, apoptosis, and ccnd1
      and myca expressions. The expressions of ccnd1 and myca were determined by RT
      PCR. Lipid peroxidation (LPO), nitric oxide (NO), and glutathione-S-transferase
      (GST) activities were determined spectrophotometrically. Apoptosis was determined
      using acridine orange staining. Locomotor activity was measured using touch
      evoked movement test. MP exposure increased malformations, LPO, apoptosis, ccnd1
      and myca expressions, and decreased GST activities and NO levels compared with
      the control group. Our findings will lead to further understanding of the
      mechanism of MP toxicity, and merit further research.

PMID- 29360219
TI  - Collagen proteins exchange O with demineralisation and gelatinisation reagents
      and also with atmospheric moisture.
AB  - RATIONALE: The oxygen isotope composition of collagen proteins is a potential
      indicator of adult residential location, useful for provenancing in ecology,
      archaeology and forensics. In acidic solution, proteins can exchange O from
      carboxylic acid moieties with reagent O. This study investigated whether this
      exchange occurs during demineralisation and gelatinisation preparation of
      bone/ivory collagen. METHODS: EDTA and HCl demineralisation or gelatinisation
      reagents were made up in waters with different delta18 O values, and were used to
      extract collagen from four skeletal tissue samples. Aliquots of extracted
      collagen were exposed to two different atmospheric waters, at 120 degrees C and
      ambient temperature, and subsequently dried in a vacuum oven at 40 degrees C or
      by freeze drying. Sample delta18 O values were measured by HT/EA pyrolysis-IRMS
      using a zero-blank autosampler. RESULTS: Collagen samples exchanged O with both
      reagent waters and atmospheric water, which altered sample delta18 O values.
      Exchange with reagent waters occurred in all extraction methods, but was greater
      at lower pH. Damage to the collagen samples during extraction increased O
      exchange. The nature of exchange of O with atmospheric water depended on the
      temperature of exposure: kinetic fractionation of O was identified at 120 degrees
      C but not at ambient temperature. Exchange was difficult to quantify due to high
      variability of delta18 O value between experimental replicates. CONCLUSION:
      Studies of delta18 O values in collagen proteins should avoid extraction methods
      using acid solutions.

PMID- 29360221
TI  - Neuromuscular disease-specific questionnaire to assess quality of life in
      patients with chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - To date, generic questionnaires have been used to investigate quality of life
      (QoL) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
      patients. Although these measures are very useful, they are not usually precise
      enough to measure all specific characteristics of the disease. Our aim was to
      investigate QoL using the neuromuscular disease-specific questionnaire
      (individualized neuromuscular quality of life, INQoL) in a large cohort of
      patients with CIDP. Our study comprised 106 patients diagnosed with CIDP. INQoL
      questionnaire, Medical Research Council (MRC) sum score, Inflammatory Neuropathy
      Cause and Treatment (INCAT) disability score, Visual Analogue Pain Scale, Beck
      Depression Inventory, and Krupp's Fatigue Severity Scale were used in our study.
      Physical domains of INQoL were more affected than mental, and the overall score
      was 57 +/- 25. Significant predictors of higher INQoL score in our patients with
      CIDP were severe fatigue (beta = 0.35, p < 0.01), higher INCAT disability score
      at time of testing (beta = 0.29, p < 0.01), and being unemployed/retired (beta =
      0.22, p < 0.05). QoL was reduced in our cohort of CIDP patients, which was more
      pronounced in physical segments. Patients with fatigue, more severe disability,
      and unemployed/retired need special attention of neurologists because they could
      be at greater risk to have worse QoL.

PMID- 29360225
TI  - Olfactory dysfunction and cognition among older adults in the United States.
AB  - BACKGROUND: In this work we assess the association between olfactory dysfunction
      and cognition in a nationally representative sample of older adults in the United
      States. METHODS: Participants aged >=60 years (n = 1236) from the 2013-2014
      National Health and Nutritional Examination Survey underwent both olfactory and
      cognitive testing. Olfaction was assessed by both objective test (8-odor Pocket
      Smell Test: smell impairment defined as score <=2) and self-report. Cognitive
      assessment consisted of the Digit Symbol Substitution Test (DSST), the Animal
      Fluency Test, and the Consortium to Establish a Registry for Alzheimer's Disease
      (CERAD). Regression models were used to examine the association between olfaction
      and cognition while adjusting for demographics, cardiovascular factors, and
      associated medical history. RESULTS: The prevalence of smell impairment in US
      older adults was 18.0% (95% confidence interval [CI], 14.0-22.0%) and 22.0% (95%
      CI, 18.5-25.6%) based on objective smell test and self-report, respectively. In a
      multivariate model adjusted for relevant factors, low smell test scores were
      consistently associated with low scores on cognitive assessments, with a DSST
      score difference of -1.5 (95% CI, -2.2 to -0.8), Animal Fluency Test score
      difference of -0.4 (95% CI, -0.7 to -0.1), and CERAD Word List score difference
      of -0.4 (95% CI, -0.6 to -0.2) per 1-point decrease in smell test score. There
      was no association between self-reported smell impairment and cognition.
      CONCLUSION: Objectively measured olfactory dysfunction is independently
      associated with cognitive impairment. These findings are consistent with previous
      studies and suggest the utility of objective olfactory tests as an indicator for
      cognitive impairment as compared with self-reported olfactory dysfunction, which
      is an uncertain indicator.

PMID- 29360226
TI  - Modulation of transport and metabolism of bile acids and bilirubin by chlorogenic
      acid against hepatotoxicity and cholestasis in bile duct ligation rats:
      involvement of SIRT1-mediated deacetylation of FXR and PGC-1alpha.
AB  - BACKGROUND: The purpose of the present study was to investigate the effect and
      potential mechanism of chlorogenic acid (CA) on liver injury induced by
      cholestasis in a rat model of bile duct ligation (BDL). METHODS: Rats received
      vehicle or CA (20, 50, or 100 mg/kg per day) orally for 3 days. On the 4th day,
      the rats underwent sham or BDL surgery, and were orally administrated vehicle or
      CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR
      and western blot. RESULTS: After BDL, plasma levels of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and total bile
      acids (TBA) were increased and typical pathological changes were observed in
      liver morphology. Hepatic uptake transporters (Ntcp, Oatp 1a4, and Oatp 1b2) were
      downregulated, while efflux transporters (Bsep and Mrp 2/3/4) were upregulated.
      BDL inhibited the expressions of Cyp7a1, Cyp8b1, and Cyp27a1 and induced Ugt1a1.
      CA treatment decreased ALT, AST, TBIL, and TBA (P < 0.05) and alleviated the
      liver pathological changes. The degree of expression changes in the transporters
      and enzymes was extended by CA (P < 0.05). SIRT1 protein was induced after CA
      treatment in BDL rats. CONCLUSIONS: Chlorogenic acid attenuated hepatotoxicity
      and cholestasis by decreasing the uptake and synthesis of bilirubin and bile
      acids and accelerating the metabolism and efflux of bilirubin and bile acids.

PMID- 29360227
TI  - Liver "lobe neutrality" in the era of donor safety. Could "safe" be safer?

PMID- 29360229
TI  - Errata.

PMID- 29360230
TI  - Capnocytophaga keratitis in dogs: clinical, histopathologic, and microbiologic
      features of seven cases.
AB  - OBJECTIVE: To describe the clinical, microbiologic, and histopathologic features
      of Capnocytophaga keratitis in dogs. ANIMALS STUDIED: Seven dogs with naturally
      acquired Capnocytophaga keratitis. PROCEDURES: Medical records of dogs with a
      clinical diagnosis of keratitis and corneal cultures positive for Capnocytophaga
      spp. were reviewed. Dog signalment, medical history, clinical findings, and
      diagnostic assay results were recorded. RESULTS: Breeds included Boston terrier
      (n = 3 dogs), Rat terrier (n = 2), and single cases of mixed breed and Pug. All
      dogs examined had expansive corneal ulceration involving the majority of the
      corneal surface. Marked corneal infiltrates, keratomalacia, and hypopyon were
      present. Progression of corneal disease was rapid with extensive dissolution of
      the corneal stroma. Corneal lesions progressed to catastrophic perforations
      within 24 h of the initial examination in three dogs, requiring enucleation. One
      globe was enucleated after failure to resolve with long-term medical therapy.
      Globes and vision were retained in three dogs following aggressive medical
      therapy (two dogs) or 360 degrees  conjunctival graft surgery (one dog).
      Capnocytophaga cynodegmi, Capnocytophaga canimorsus, or unspeciated
      Capnocytophaga spp. were cultured from corneal samples of all dogs. Long, thin,
      gram-negative rods were present during cytological evaluation of the cornea in
      some dogs. Histopathologic evaluation of enucleated globes revealed severe and
      diffuse neutrophilic and collagenolytic keratitis. CONCLUSIONS: Capnocytophaga
      keratitis is a severe, rapidly progressive corneal infection in dogs that is
      associated with diffuse corneal involvement, extensive keratomalacia, and a
      relatively poor prognosis. Clinical features of canine Capnocytophaga keratitis
      are similar to human cases of this infection.

PMID- 29360232
TI  - Errata.

PMID- 29360234
TI  - Dead cells certainly do matter, particularly when they can speak from the grave.

PMID- 29360235
TI  - Obviating the need for sternotomy: Safety and effectiveness of microdebrider use
      for retrosternal goiter.
AB  - BACKGROUND: Most retrosternal goiter surgical removal can be performed via a
      transcervical approach. However, it is often a challenging procedure, which might
      include sternotomy. METHODS: We describe a surgical technique using a
      microdebrider for intracapsular volume reduction that precedes an extracapsular
      thyroidectomy, thereby avoiding the need for sternotomy, with decreased morbidity
      and risk. The procedure is described in detail with 2 representative cases and a
      summary of our experience in 26 cases. RESULTS: Twenty-six patients with
      retrosternal goiters are included in our cohort. None of the patients needed a
      sternotomy, and no major or permanent complications occurred. The average length
      of hospital stay was 4.30 days after total thyroidectomy and 2.57 days after
      hemithyroidectomy. CONCLUSION: The use of a microdebrider for intracapsular
      volume reduction thyroidectomy is extremely helpful for transcervical removal of
      retrosternal goiters in selected cases, and avoids the need for sternotomy, which
      is especially beneficial in elderly patients, and those with comorbidities for
      whom sternotomy should be avoided.

PMID- 29360236
TI  - The NMR solution structure of Mycobacterium tuberculosis F-ATP synthase subunit
      epsilon provides new insight into energy coupling inside the rotary engine.
AB  - : Mycobacterium tuberculosis (Mt) F1 F0 ATP synthase (alpha3 :beta3
      :gamma:delta:epsilon:a:b:b':c9 ) is essential for the viability of growing and
      nongrowing persister cells of the pathogen. Here, we present the first NMR
      solution structure of Mtepsilon, revealing an N-terminal beta-barrel domain (NTD)
      and a C-terminal domain (CTD) composed of a helix-loop-helix with helix 1 and -2
      being shorter compared to their counterparts in other bacteria. The C-terminal
      amino acids are oriented toward the NTD, forming a domain-domain interface
      between the NTD and CTD. The Mtepsilon structure provides a novel mechanistic
      model of coupling c-ring- and epsilon rotation via a patch of hydrophobic
      residues in the NTD and residues of the CTD to the bottom of the catalytic alpha3
      beta3 -headpiece. To test our model, genome site-directed mutagenesis was
      employed to introduce amino acid changes in these two parts of the epsilon
      subunit. Inverted vesicle assays show that these mutations caused an increase in
      ATP hydrolysis activity and a reduction in ATP synthesis. The structural and
      enzymatic data are discussed in light of the transition mechanism of a compact
      and extended state of Mtepsilon, which provides the inhibitory effects of this
      coupling subunit inside the rotary engine. Finally, the employment of these data
      with molecular docking shed light into the second binding site of the drug
      Bedaquiline. DATABASE: Structural data are available in the PDB under the
      accession number 5YIO.

PMID- 29360238
TI  - Concentration of filaggrin monomers, its metabolites and corneocyte surface
      texture in individuals with a history of atopic dermatitis and controls.
AB  - BACKGROUND: Atopic dermatitis (AD) is characterized by skin barrier dysfunction.
      Notably, a high number of nano-scale protrusions on the surface of corneocytes,
      which can be expressed by the Dermal Texture Index (DTI), were recently
      associated with paediatric AD, loss-of-function mutations in filaggrin gene (FLG)
      and reduced levels of natural moisturizing factors (NMF). No study has so far
      examined the association between these parameters and monomeric filaggrin levels
      in adults. OBJECTIVE: To determine DTI, monomeric filaggrin and NMF in healthy
      controls and a group of patients with controlled dermatitis. METHODS: A total of
      67 adults (20 healthy controls and 47 dermatitis patients) were included. In the
      patient population, a personal history of AD was diagnosed by the U.K. Working
      Party's Diagnostic Criteria. All participants were tested for FLG mutations
      (R501X, 2282del4, R2447X). Transepidermal water loss, monomeric filaggrin, DTI
      and NMF were measured. RESULTS: In the patient population, 78.7% (37/47) had a
      history of AD and 59.5% (28/47) had FLG mutations. Patients had significantly
      higher levels of DTI and significantly lower levels of monomeric filaggrin and
      NMF compared to the 20 healthy controls. Among patients, reduced level of
      monomeric filaggrin and NMF correlated with the presence of FLG mutations and
      clinical phenotypes such as xerosis, palmar hyperlinearity and AD. Among healthy
      controls, DTI was significantly higher in the oldest age group compared to the
      two younger age groups. CONCLUSION: A significant difference in DTI, monomeric
      filaggrin and NMF levels was found when comparing dermatitis patients with
      healthy controls. These findings suggest that even mild dermatitis or non-visible
      inflammation has a significant and negative effect on the skin barrier as
      inflammation is known to reduce filaggrin levels. DTI was significantly increased
      in aged individuals in the healthy control group, suggesting a gradual change in
      corneocyte morphology with age.

PMID- 29360239
TI  - Silicon Carbide Nanoparticles as an Effective Bioadhesive to Bond Collagen
      Containing Composite Gel Layers for Tissue Engineering Applications.
AB  - Additive manufacturing via layer-by-layer adhesive bonding holds much promise for
      scalable manufacturing of tissue-like constructs, specifically scaffolds with
      integrated vascular networks for tissue engineering applications. However, there
      remains a lack of effective adhesives capable of composite layer fusion without
      affecting the integrity of patterned features. Here, the use of silicon carbide
      is introduced as an effective adhesive to achieve strong bonding (0.39 +/- 0.03
      kPa) between hybrid hydrogel films composed of alginate and collagen. The
      techniques have allowed us to fabricate multilayered, heterogeneous constructs
      with embedded high-resolution microchannels (150 um-1 mm) that are precisely
      interspaced (500-600 um). Hydrogel layers are effectively bonded with silicon
      carbide nanoparticles without blocking the hollow microchannels and high cell
      viability (90.61 +/- 3.28%) is maintained within the scaffold. Nanosilica is also
      tested and found to cause clogging of smaller microchannels when used for
      interlayer bonding, but is successfully used to attach synthetic polymers (e.g.,
      Tygon) to the hydrogels (32.5 +/- 2.12 mN bond strength). This allows us to form
      inlet and outlet interconnections to the gel constructs. This ability to
      integrate hollow channel networks into bulk soft material structures for
      perfusion can be useful in 3D tissue engineering applications.

PMID- 29360237
TI  - One-year weight losses in the Tianjin Gestational Diabetes Mellitus Prevention
      Programme: A randomized clinical trial.
AB  - AIMS: To report the weight loss findings after the first year of a lifestyle
      intervention trial among women with gestational diabetes mellitus (GDM). METHODS:
      A total of 1180 women with GDM were randomly assigned (1:1) to receive a 4-year
      lifestyle intervention (intervention group, n = 586) or standard care (control
      group, n = 594) between August 2009 and July 2011. Major elements of the
      intervention included 6 face-to-face sessions with study dieticians and two
      telephone calls in the first year, and two individual sessions and two telephone
      calls in each subsequent year. RESULTS: Among 79% of participants who completed
      the year 1 trial, mean weight loss was 0.82 kg (1.12% of initial weight) in the
      intervention group and 0.09 kg (0.03% of initial weight) in the control group (P
      = .001). In a prespecified subgroup analysis of people who completed the trial,
      weight loss was more pronounced in women who were overweight (body mass index
      >=24 kg/m2 ) at baseline: mean weight loss 2.01 kg (2.87% of initial weight) in
      the intervention group and 0.44 kg (0.52% of initial weight) in the control group
      (P < .001). Compared with those in the control group, women in the intervention
      group had a greater decrease in waist circumference (1.76 cm vs 0.73 cm; P =
      .003) and body fat (0.50% vs 0.05% increase; P = .001). CONCLUSION: The 1-year
      lifestyle intervention led to significant weight losses after delivery in women
      who had GDM, and the effect was more pronounced in women who were overweight at
      baseline.

PMID- 29360240
TI  - Effects of intramedullary nails composed of a new beta-type Ti-Nb-Sn alloy with
      low Young's modulus on fracture healing in mouse tibiae.
AB  - The influence of Young's moduli of materials on the fracture healing process
      remains unclear. This study aimed to assess the effects of intramedullary nails
      composed of materials with low Young's moduli on fracture repair. We previously
      developed a beta-type Ti-Nb-Sn alloy with low Young's modulus close to that of
      human cortical bone. Here, we prepared two Ti-Nb-Sn alloys with Young's moduli of
      45 and 78 GPa by heat treatment, and compared their effects on fracture healing.
      Fracture and nailing were performed in the right tibiae of C57BL/6 mice. The bone
      healing process was evaluated by microcomputed tomography (micro-CT),
      histomorphometry, and RT-PCR. We found larger bone volumes of fracture callus in
      the mice treated with the 45-GPa Ti-Nb-Sn alloy as compared with the 78-GPa Ti-Nb
      Sn alloy in micro-CT analyses. This was confirmed with histology at day 14, with
      accelerated new bone formation and cartilage absorption in the 45-GPa Ti-Nb-Sn
      group compared with the 78-GPa Ti-Nb-Sn group. Acp5 expression was lower in the
      45-GPa Ti-Nb-Sn group than in the 78-GPa Ti-Nb-Sn group at day 10. These findings
      indicate that intramedullary fixation with nails with a lower Young's modulus
      offer a greater capacity for fracture repair. Our 45-GPa Ti-Nb-Sn alloy is a
      promising material for fracture treatment implants. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2841-2848, 2018.

PMID- 29360241
TI  - Exploring the frequency and location of prescribing errors in the use of topical
      glaucoma medications.
AB  - IMPORTANCE: Very little is known about health-care professional related
      prescribing errors within the glaucoma setting. BACKGROUND: This study aims to
      quantify these errors and to explore where they occur along the prescribing
      pathway. DESIGN: Cross-sectional study of patients attending a specialty glaucoma
      clinic over a 5-month period. PARTICIPANTS: Data was collected for 109 patients.
      METHODS: We compared glaucoma drop regimes from four different sources: As
      documented in the hospital notes for the last appointment, the letter sent to the
      General Practitioner (GP), patient's self-reporting and bottles/prescriptions
      brought to the clinic appointment. MAIN OUTCOME MEASURES: Discrepancies were
      identified and errors were grouped into one of four categories depending on where
      in the prescribing pathway they occurred: Incorrect prescribing of the drops by
      the clinician, incorrect prescribing of the drops by the GP/failure to provide a
      repeat prescription, incorrect dispensing of the drops by the pharmacist and
      possible non-adherence by the patient. RESULTS: There was a total of 217
      individual prescription items involving 266 active ingredients. Seventy-one
      prescription items out of 217 (33%) had an error, of this 53 (75%) were due to
      possible patient non-adherence and 18 (25%) were process related errors made by
      health-care professionals. CONCLUSIONS AND RELEVANCE: An error was identified in
      33% of prescriptions. About 8.3% of prescriptions had a health-care professional
      related process error. These errors are preventable and recognition of these is
      important to maximize drop adherence and minimize disease progression, requiring
      increased consultations and interventions with quality of life and health
      economic consequences.

PMID- 29360242
TI  - The Grieving Nursing Diagnoses in the Primary Healthcare Setting.
AB  - PURPOSE: To estimate the prevalence of Grieving, risk for Complicated Grieving,
      and Complicated Grieving in the primary care setting. METHODS: Retrospective
      epidemiological study, analyzing data from electronic health records (EHR).
      FINDINGS: A total of 84% of the 9,063 records had diagnostic labels without
      defining characteristics, related factors, or risk factors. A larger frequency of
      complicated grieving was found in deceased mourners. CONCLUSIONS: The grieving
      epidemiology opens new chances for the research using data from EHR. PRACTICE
      IMPLICATIONS: The adequacy of the records is essential to develop a profile of
      the patient at risk of complications after the loss. This research is an
      important step to build an epidemiological basis for nursing diagnosis of
      grieving in the primary health care setting.

PMID- 29360244
TI  - Historical aspects of studies on roles of the inflammasome in the pathogenesis of
      periodontal diseases.
AB  - The proinflammatory cytokine interleukin-1beta (IL-1beta) is produced as inactive
      proIL-1beta and then processed by caspase-1 to become active. In 2002, it was
      demonstrated that the intracellular multiprotein complex known as the
      inflammasome functions as a molecular platform to trigger activation of caspase
      1. Inflammasomes are known to function as intracellular sensors for a broad
      spectrum of various pathogen-associated and damage-associated molecular patterns.
      In 1985, it was demonstrated that Porphyromonas gingivalis, a representative
      bacterium causing chronic periodontitis, induces IL-1 production by murine
      peritoneal macrophages. Since then, many studies have suggested that IL-1,
      particularly IL-1beta plays key roles in the pathogenesis of periodontal
      diseases. However, the term "inflammasome" was not used until the involvement of
      inflammasomes in periodontal disease was suggested in 2009. Several subsequent
      studies on the roles of the inflammasome in the pathogenesis of periodontal
      diseases have been published. Interestingly, two contradictory reports on the
      modulation of inflammasomes by P. gingivalis have been published. Some papers
      have described how P. gingivalis activates the inflammasome to produce IL-1beta
      whereas some stated that P. gingivalis inhibits inflammasome activation to
      subvert immune responses. Several lines of evidence have suggested that the
      inflammasome activation is modulated by periodontopathic bacteria other than P.
      gingivalis. Hence, studies on the roles of inflammasomes in the pathogenesis of
      periodontal diseases began only 8 years ago and many pathological roles of
      inflammasomes remain to be clarified.

PMID- 29360245
TI  - Memorial: Emmanuelle Caron 1967-2009.

PMID- 29360246
TI  - Abstracts from the Third International Damage Associated Molecular Pattern
      Molecules (DAMPs) and Alarmins Symposium.

PMID- 29360248
TI  - Acute Kidney Injury: Who Should be Followed-up and by Whom?

PMID- 29360250
TI  - Impact of electronic health record-based, pharmacist-driven valganciclovir dose
      optimization in solid organ transplant recipients.
AB  - BACKGROUND: Prophylaxis with valganciclovir reduces the incidence of
      cytomegalovirus (CMV) infection following solid organ transplant (SOT). Under
      dosing of valganciclovir is associated with an increased risk of CMV infection
      and development of ganciclovir-resistant CMV. METHODS: An automated electronic
      health record (EHR)-based, pharmacist-driven program was developed to optimize
      dosing of valganciclovir in solid organ transplant recipients at a large
      transplant center. Two cohorts of kidney, pancreas-kidney, and liver transplant
      recipients from our center pre-implementation (April 2011-March 2012, n = 303)
      and post-implementation of the optimization program (September 2012-August 2013,
      n=263) had demographic and key outcomes data collected for 1 year post
      transplant. RESULTS: The 1-year incidence of CMV infection dropped from 56
      (18.5%) to 32 (12.2%, P = .05) and the incidence of breakthrough infections on
      prophylaxis was cut in half (61% vs 34%, P = .03) after implementation of the
      dose optimization program. The hazard ratio of developing CMV was 1.64 (95% CI
      1.06-2.60, P = .027) for the pre-implementation group after adjusting for
      potential confounders. The program also resulted in a numerical reduction in the
      number of ganciclovir-resistant CMV cases (2 [0.7%] pre-implementation vs 0 post
      implementation). CONCLUSIONS: An EHR-based, pharmacist-driven valganciclovir dose
      optimization program was associated with reduction in CMV infections.

PMID- 29360249
TI  - Pretreatment with standard-dose intravenous methylprednisolone does not improve
      outcomes in newly diagnosed immune thrombocytopenia (ITP).
AB  - OBJECTIVE: To assess the benefits and harms to initiate corticosteroids with
      intravenous methylprednisolone at a conventional dose (1 mg/kg/d) to treat adults
      with immune thrombocytopenia (ITP). METHODS: Population stemmed from the
      prospective multicenter CARMEN registry and included newly diagnosed hospitalized
      ITP adults with platelet counts<30 * 109 /L. We compared the patients treated
      with conventional-dose methylprednisolone (CDMP) before continuing with oral
      prednisone to patients treated with just conventional-dose oral prednisone
      (CDOP). The primary outcome was the time until response. Secondary outcomes were
      time until complete response, response rate, complete response rate, duration of
      hospital stay, and occurrence of adverse drug reactions. Analyzes were adjusted
      for propensity score and for exposure to intravenous immunoglobulin. RESULTS:
      Among the included 87 patients, the median time to response was 3 days in the
      CDMP group vs 4 in the CDOP group (adjusted hazard ratio [aHR]: 1.35; 95%CI: 0.76
      2.41). The CDMP group had an earlier complete response (aHR: 2.29; 95%CI: 1.20
      4.36). There was no difference between the groups regarding other secondary
      outcomes. CONCLUSIONS: Initiating methylprednisolone at a conventional dose
      provided no significant benefit compared to giving oral prednisone only to adults
      with ITP.

PMID- 29360255
TI  - Erratum.

PMID- 29360254
TI  - Intravenous thrombolysis for acute ischaemic stroke in patients on direct oral
      anticoagulants.
AB  - BACKGROUND AND PURPOSE: Whereas intravenous thrombolysis (IVT) is allowed for
      acute ischaemic stroke in patients on vitamin K antagonists with international
      normalized ratio <=1.7, there are no similar recommendations for patients on
      direct oral anticoagulants (DOACs), notably due to the lack of coagulation tests
      to assess the therapeutic effects. Although the literature is scarce, consisting
      of small case series and retrospective studies, considering the frequency of this
      situation the French Vascular Neurology Society and the French Study Group on
      Haemostasis and Thrombosis have worked on a joint position paper to provide a
      practical position regarding the emergency management of ischaemic stroke in
      patients on DOACs. METHOD: Based on a review of the literature, the authors wrote
      a first text that was submitted to a broad panel of members from the two
      societies. The text was then amended by the authors to address experts' comments
      and to reach a consensus. RESULTS: In patients with normal renal function and who
      stopped the DOAC for at least 48 h, the management should not differ from that in
      patients without oral anticoagulant. In patients who are still on DOACs,
      mechanical thrombectomy is encouraged preferentially when applicable in first
      line. Otherwise, when specific tests are available, values <50 ng/ml indicate
      that IVT is allowed. In the absence of specific tests, standard tests (thrombin
      time, prothrombin time and activated partial thromboplastin time) can be used for
      dabigatran and rivaroxaban, although interpretation of these tests may be less
      reliable. In some patients on dabigatran, idarucizumab may be used before IVT.
      CONCLUSIONS: In this expert opinion paper, it is suggested that IVT can be
      performed in patients selected according to the time elapsed since the drug was
      last taken, renal function, type of hospital where the patient is admitted and
      plasma concentration of DOAC.

PMID- 29360259
TI  - Classifiers and their Metrics Quantified.
AB  - Molecular modeling frequently constructs classification models for the prediction
      of two-class entities, such as compound bio(in)activity, chemical property
      (non)existence, protein (non)interaction, and so forth. The models are evaluated
      using well known metrics such as accuracy or true positive rates. However, these
      frequently used metrics applied to retrospective and/or artificially generated
      prediction datasets can potentially overestimate true performance in actual
      prospective experiments. Here, we systematically consider metric value surface
      generation as a consequence of data balance, and propose the computation of an
      inverse cumulative distribution function taken over a metric surface. The
      proposed distribution analysis can aid in the selection of metrics when
      formulating study design. In addition to theoretical analyses, a practical
      example in chemogenomic virtual screening highlights the care required in metric
      selection and interpretation.

PMID- 29360260
TI  - Diet soft drink is associated with increased odds of proliferative diabetic
      retinopathy.
AB  - IMPORTANCE: While consumption of soft drink may increase the risk of
      cardiovascular disease, the relationship between soft drink consumption and
      diabetes complications is unknown. BACKGROUND: To explore the association between
      regular and diet soft drink consumption, and diabetic retinopathy (DR) and
      diabetic macular oedema (DME). DESIGN: Clinical, cross-sectional study.
      PARTICIPANTS: Adult patients with diabetes recruited from a tertiary eye hospital
      (Melbourne, Australia) answered a Food Frequency Questionnaire. METHODS: None,
      moderate and high soft drink consumption was defined as <1, 1-4 and >4
      cans/bottles (375 mL) per week, respectively. Due to missing data, data were
      imputed using the multiple imputation chained equation procedure. Multivariable
      logistic regression models determined the associations between soft drink
      consumption, and presence and severity of DR/DME. MAIN OUTCOME MEASURES: Presence
      and severity of DR/DME. RESULTS: Of the 609 participants (mean age +/- standard
      deviation: 64.6 +/- 11.6 years; males = 210), 285 (46.8%) and 190 (31.2%)
      consumed diet and regular soft drink, respectively. A total of 230 (37.8%), 36
      (5.9%), 154 (25.3%), 28 (4.6%) and 146 (24.0%) had no DR, mild non-proliferative
      DR (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR), respectively.
      High diet soft drink consumption was independently associated with increased
      likelihood of having PDR (odds ratio = 2.51, 95% confidence interval = 1.05
      5.98), compared to no consumption. In contrast, regular soft drink was not
      associated with DR or DME. CONCLUSIONS AND RELEVANCE: Consuming >4 cans (1.5
      L)/week of diet soft drink is associated with a more than twofold risk of having
      PDR in patients with diabetes. Longitudinal studies are needed to further
      elucidate the association and its underpinning mechanisms.

PMID- 29360258
TI  - Liver function and dysfunction - a unique window into the physiological reach of
      ER stress and the unfolded protein response.
AB  - The unfolded protein response (UPR) improves endoplasmic reticulum (ER) protein
      folding in order to alleviate stress. Yet it is becoming increasingly clear that
      the UPR regulates processes well beyond those directly involved in protein
      folding, in some cases by mechanisms that fall outside the realm of canonical UPR
      signaling. These pathways are highly specific from one cell type to another,
      implying that ER stress signaling affects each tissue in a unique way. Perhaps
      nowhere is this more evident than in the liver, which-beyond being a highly
      secretory tissue-is a key regulator of peripheral metabolism and a uniquely
      proliferative organ upon damage. The liver provides a powerful model system for
      exploring how and why the UPR extends its reach into physiological processes that
      occur outside the ER, and how ER stress contributes to the many systemic diseases
      that involve liver dysfunction. This review will highlight the ways in which the
      study of ER stress in the liver has expanded the view of the UPR to a response
      that is a key guardian of cellular homeostasis outside of just the narrow realm
      of ER protein folding.

PMID- 29360261
TI  - Advanced endoscopic imaging for diagnosis of inflammatory bowel diseases: Present
      and future perspectives.
AB  - Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases
      (IBD) causing severe damage of the luminal gastrointestinal tract. Differential
      diagnosis between both disease entities is sometimes awkward requiring a
      multifactorial pathway, including clinical and laboratory data, radiological
      findings, histopathology and endoscopy. Apart from disease diagnosis, endoscopy
      in IBD plays a major role in prediction of disease severity and extent (i.e.
      mucosal healing) for tailored patient management and for screening of colitis
      associated cancer and its precursor lesions. In this state-of-the-art review, we
      focus on current applications of endoscopy for diagnosis and surveillance of IBD.
      Moreover, we will discuss the latest guidelines on surveillance and provide an
      overview of the most recent developments in the field of endoscopic imaging and
      IBD.

PMID- 29360262
TI  - Immunocompromised patients with metastatic cutaneous nodal squamous cell
      carcinoma of the head and neck: Poor outcome unrelated to the index lesion.
AB  - BACKGROUND: Immunocompromised patients with metastatic cutaneous nodal head and
      neck squamous cell carcinoma (HNSCC) have worse outcomes compared to the
      immunocompetent. The purpose of this study was to investigate the characteristics
      of the primary cutaneous squamous cell carcinoma (SCC), nodal pathology, and
      outcome between these 2 groups. METHODS: Analysis of a prospective database was
      performed. A 2:1 pooled analysis selected 46 immunocompetent patients matched
      with 23 immunocompromised patients. Overall survival (OS) and relapse-free
      survival (RFS) were calculated using the Kaplan-Meier method. RESULTS: No
      significant difference was found in the primary tumor characteristics between the
      2 groups. In the immunocompromised group, RFS (hazard ratio [HR] 2.70; P = .01)
      and OS (HR 2.32; P = .04) were significantly worse. Extracapsular spread was
      present in 100% of the immunocompromised patients. CONCLUSION: No significant
      difference was identified in the primary cutaneous SCC between the
      immunocompetent and immunocompromised patients. Immunosuppression predicted worse
      outcome.

PMID- 29360263
TI  - Usefulness of Sweep Imaging With Fourier Transform for Evaluation of Cortical
      Bone in Diabetic Rats.
AB  - BACKGROUND: Diabetes decreases bone strength, possibly because of cortical bone
      changes. Sweep imaging with Fourier transform (SWIFT) has been reported to be
      useful for cortical bone evaluation. PURPOSE: To evaluate cortical bone changes
      in diabetic rats using SWIFT, assess the usefulness of this technique through
      comparisons with microcomputed tomography (MUCT) and conventional MRI, and
      clarify the mechanism underlying cortical bone changes using histomorphometry
      STUDY TYPE: Animal cohort. ANIMAL MODEL: 8-week-old male Wistar/ST rats (N = 36)
      were divided into diabetes (induced by streptozotocin injection) and control
      groups. FIELD STRENGTH/SEQUENCE: 7.04T MRI, SWIFT. ASSESSMENT: Six animals from
      each group were sacrificed at 2, 4, and 8 weeks after injection. Tibial bones
      were extracted and evaluated using MUCT and MRI. The cortical bone mineral
      density (BMD) was measured using MUCT. Proton density-weighted imaging (PDWI) and
      SWIFT were also performed. The signal-to-noise ratio (SNR) was calculated for
      each acquisition. The bone formation rate was evaluated using histomorphometry.
      STATISTICAL TESTS: Findings at each timepoint were compared using Mann-Whitney U
      tests. RESULTS: Cortical BMD was significantly lower in the diabetes group than
      in the control group only at 8 weeks (P < 0.05). At all timepoints, PDWI-SNR
      showed no significant differences between groups (P = 0.59, 0.70, and 0.82 at 2,
      4, and 8 weeks, respectively). SWIFT-SNR was significantly lower in the diabetes
      group than in the control group (P < 0.05 at 2 and 4 weeks and P < 0.01 at 8
      weeks), and the bone formation rate was significantly lower in the diabetes group
      than in the control group (P < 0.01 for all). DATA CONCLUSION: SWIFT can detect
      cortical bone changes even before a decline in the cortical BMD in a diabetic
      model. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING
      2018;48:389-397.

PMID- 29360264
TI  - Diminished respiratory sinus arrhythmia response in infants later diagnosed with
      autism spectrum disorder.
AB  - : Indicators of risk for developing Autism Spectrum Disorder (ASD) are difficult
      to detect within the first year of life. In this study, infants who were
      originally followed prospectively to examine general developmental risks due to
      substance exposure interacted with their mother and an unfamiliar experimenter
      for 2-min episodes at 4 months of age. Electrocardiogram was collected to measure
      respiratory sinus arrhythmia (RSA) and the session was video recorded for
      behavioral coding. Two groups of infants were compared: infants with a diagnosed
      ASD outcome (N = 8) and matched controls (N = 186). Infants were compared on mean
      RSA and infant behavioral codes for each 2-min episode. No significant group
      differences were revealed on RSA or behavior during interactions between the
      infants and mothers. However, in response to play with a stranger, infants with
      an ASD outcome had lower RSA (M = 2.49, 95% CI [2.30, 2.98]) than controls (M =
      3.12, 95% CI [3.06, 3.18]). During the interaction with a stranger, lower RSA
      response was associated with more protesting behaviors (P < 0.01), whereas higher
      RSA response was associated with more social monitoring (P = 0.001). Lower RSA
      suggests that 4-month-old infants later diagnosed with ASD exhibited poorer
      autonomic regulation during interaction with an unfamiliar adult than did
      controls. Physiological regulation during interactions with a new social partner
      may be disrupted early in infancy in children with ASD, as indicated here by
      lower RSA, and therefore be a potential target for developing early risk
      screening tools for ASD. Autism Res 2018, 11: 726-731. (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism Spectrum
      Disorder (ASD) emerges within the first years of life; however, it is difficult
      to identify children who will develop autism before 12 months of age based on
      behavioral measures. In a study of infants who were followed from birth, infants
      who were later diagnosed with ASD had poorer physiological regulation during play
      with a new adult. With additional evidence, poorer physiological regulation may
      function as an early sign of ASD risk.

PMID- 29360265
TI  - Effect of NADPH oxidase 1 and 4 blockade in activated human retinal endothelial
      cells.
AB  - BACKGROUND: Over-production of reactive oxygen species (ROS) and resulting
      oxidative stress contribute to retinal damage in vascular diseases that include
      diabetic retinopathy, retinopathy of prematurity and major retinal vessel
      occlusions. NADPH oxidase (Nox) proteins are professional ROS-generating enzymes,
      and therapeutic targeting in these diseases has strong appeal. Pharmacological
      inhibition of Nox4 reduces the severity of experimental retinal vasculopathy. We
      investigated the potential application of this drug approach in humans. METHODS:
      Differential Nox enzyme expression was studied by real-time-quantitative
      polymerase chain reaction in primary human retinal endothelial cell isolates and
      a characterized human retinal endothelial cell line. Oxidative stress was
      triggered chemically in endothelial cells, by treatment with
      dimethyloxalylglycine (DMOG; 100 MUM); Nox4 and vascular endothelial growth
      factor (VEGFA) transcript were measured; and production of ROS was detected by
      2',7'-dichlorofluorescein. DMOG-stimulated endothelial cells were treated with
      two Nox1/Nox4 inhibitors, GKT136901 and GKT137831; cell growth was monitored by
      DNA quantification, in addition to VEGFA transcript and ROS production. RESULTS:
      Nox4 (isoform Nox4A) was the predominant Nox enzyme expressed by human retinal
      endothelial cells. Treatment with DMOG significantly increased endothelial cell
      expression of Nox4 over 72 h, accompanied by ROS production and increased VEGFA
      expression. Treatment with GKT136901 or GKT137831 significantly reduced DMOG
      induced ROS production and VEGFA expression by endothelial cells, and the
      inhibitory effect of DMOG on cell growth. CONCLUSIONS: Our findings in
      experiments on activated human retinal endothelial cells provide translational
      corroboration of studies in experimental models of retinal vasculopathy and
      support the therapeutic application of Nox4 inhibition by GKT136901 and GKT137831
      in patients with retinal vascular diseases.

PMID- 29360266
TI  - Targeting glioma stem-like cell survival and chemoresistance through inhibition
      of lysine-specific histone demethylase KDM2B.
AB  - Glioblastoma (GBM) ranks among the most lethal cancers, with current therapies
      offering only palliation. Inter- and intrapatient heterogeneity is a hallmark of
      GBM, with epigenetically distinct cancer stem-like cells (CSCs) at the apex.
      Targeting GSCs remains a challenging task because of their unique biology,
      resemblance to normal neural stem/progenitor cells, and resistance to standard
      cytotoxic therapy. Here, we find that the chromatin regulator, JmjC domain
      histone H3K36me2/me1 demethylase KDM2B, is highly expressed in glioblastoma
      surgical specimens compared to normal brain. Targeting KDM2B function genetically
      or pharmacologically impaired the survival of patient-derived primary
      glioblastoma cells through the induction of DNA damage and apoptosis, sensitizing
      them to chemotherapy. KDM2B loss decreased the GSC pool, which was potentiated by
      coadministration of chemotherapy. Collectively, our results demonstrate KDM2B is
      crucial for glioblastoma maintenance, with inhibition causing loss of GSC
      survival, genomic stability, and chemoresistance.

PMID- 29360268
TI  - The Monoclonal Anti-CD157 Antibody Clone SY11B5, Used for High Sensitivity
      Detection of PNH Clones on WBCs, Fails to Detect a Common Polymorphic Variant
      Encoded by BST-1.
AB  - BACKGROUND: CD157, encoded by BST-1, has been described as a useful flow
      cytometric marker for the analysis of paroxysmal nocturnal hemoglobinuria (PNH)
      as it is a glycosylphosphatidylinositol (GPI)-linked molecule highly expressed on
      normal monocytes and neutrophils. We and others observed isolated CD157 signal
      dropouts during intended PNH analysis. We hypothesize that these negative
      populations occur due to an antibody failure. To investigate the reason for this
      finding, we compared two different anti-CD157 antibody clones for PNH analysis.
      METHODS: We sequenced BST-1 of CD157-negative probands that are not suffering
      from PNH and expressed wild type and a discovered variant form of CD157 in HEK293
      cells. We compared the binding patterns of two different anti-CD157 antibody
      clones (SY11B5 and RF3) by flow cytometry and western blot analysis. RESULTS:
      When sequencing two CD157-negative probands we detected a common SNP
      (p.Arg145Gln) in exon 3 of BST-1. We found that only anti-CD157 antibody clone
      RF3 but not the more widely used clone SY11B5 was able to detect both, the wild
      type and the variant form of CD157 in flow cytometric experiments. CONCLUSION:
      The failure of anti-CD157 antibody clone SY11B5 to detect a common SNP can
      explain some CD157-negative cytometric data. This provides crucial knowledge for
      laboratories performing PNH analyses as such results can potentially lead to
      false-positive PNH interpretation. Our results confirm the importance of
      published PNH guidelines. (c) 2018 International Clinical Cytometry Society.

PMID- 29360267
TI  - MAD2L2 inhibits colorectal cancer growth by promoting NCOA3 ubiquitination and
      degradation.
AB  - Nuclear receptor coactivator 3 (NCOA3) is a transcriptional coactivator that has
      elevated expression in multiple tumor types, including colorectal cancer (CRC).
      However, the molecular mechanisms that regulate the tumorigenic functions of
      NCOA3 in CRC remain largely unknown. In this study, we aimed to discover and
      identify the novel regulatory proteins of NCOA3 and explore their mechanisms of
      action. Immunoprecipitation (IP) coupled with mass spectrometry (IP-MS) analysis
      was used to detect, identify, and verify the proteins that interacted with NCOA3
      in CRC cells. The biological functions of the candidate proteins and the
      underlying molecular mechanism were investigated in CRC cells and mouse model in
      vitro and in vivo. The clinical significance of NCOA3 and its interaction partner
      protein in CRC patients was also studied. We identified mitotic arrest deficient
      2-like protein 2 (MAD2L2, also known as MAD2B or REV7), with two signal peptide
      sequences of LIPLK and EVYPVGIFQK, to be an interaction partner of NCOA3.
      Overexpression of MAD2L2 suppressed the proliferation, migration, and
      clonogenicity of CRC cells by inducing the degradation of NCOA3. The mechanism
      study showed that increased MAD2L2 expression in CRC cells activated p38, which
      was required for the phosphorylation of NCOA3 that led to its ubiquitination and
      degradation by the proteasome. Moreover, we found that MAD2L2 predicted favorable
      prognosis in CRC patients. We have discovered a novel role of MAD2L2 in the
      regulation of NCOA3 degradation and proposed that MAD2L2 serves as a tumor
      suppressor in CRC.

PMID- 29360269
TI  - Fabrication of functionalized citrus pectin/silk fibroin scaffolds for skin
      tissue engineering.
AB  - In this study, novel porous three-dimensional (3D) scaffolds from silk fibroin
      (SF) and functionalized (amidated and oxidized) citrus pectin (PEC) were
      developed for skin tissue engineering applications. Crosslinking was achieved by
      Schiff's reaction in borax presence as crosslinking coordinating agent and CaCl2
      addition. After freeze-drying and methanol treatment, plasma treatment (10 W, 3
      min) was applied to remove surface skin layer formed on scaffolds. 3D matrices
      had high porosity (83%) and interconnectivity with pore size about 120 um that
      providing suitable microenvironment for cells. Modifications on PEC chain and
      crosslinking of scaffolds were verified by fourier-transform infrared
      spectroscopy (FTIR) analysis and spectrophotometric assay. Scaffolds showed low
      weight loss (21.3% in 40 days) and high water uptake ability in phosphate
      buffered saline (800% in 24 h). Mechanical properties of 3D matrices satisfied
      the stability of scaffolds under compressive stress and supported adhesion,
      proliferation and penetration of fibroblast cells. Our results suggested that
      modified PEC-SF scaffolds would be proposed for use in tissue engineered skin
      dermal substitutes. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B:
      Appl Biomater, 106B: 2625-2635, 2018.

PMID- 29360270
TI  - In Situ Probing Intracellular Drug Release from Redox-Responsive Micelles by
      United FRET and AIE.
AB  - Redox-responsive micelles are versatile nanoplatforms for on-demand drug
      delivery, but the in situ evaluation of drug release is challenging. Fluorescence
      resonance energy transfer (FRET) technique shows potential for addressing this,
      while the aggregation-caused quenching effect limits the assay sensitivity. The
      aim of the current work is to combine aggregation-induced emission (AIE) probe
      with FRET to realize drug release assessment from micelles. Tetraphenylethene
      (TPE) is selected as AIE dye and curcumin (Cur) is chosen as the model drug as
      well as FRET receptor. The drug is covalently linked to a block copolymer via the
      disulfide bond linker and TPE is also chemically linked to the polymer via an
      amide bond; the obtained amphiphilic polymer conjugate self-assembles into
      micelles with a hydrodynamic size of ~125 nm. Upon the supplement of glutathione
      or tris(2-carboxyethyl)phosphine) trigger (10 * 10-3 m), the drug release induces
      the fluorescence increase of both TPE and Cur. Accompanied with the FRET decay,
      absorption enhancement and particle size increase are observed. The same
      phenomenon is observed in MCF-7 cells. The FRET-AIE approach can be a useful
      addition to the spectrum of available methods for monitoring drug release from
      stimuli-responsive nanomedicine.

PMID- 29360272
TI  - New dimensions of asymmetric division in vertebrates.
AB  - Traditionally, we imagine that cell division gives rise to two identical daughter
      cells. Nevertheless, all cell divisions, to some degree, display asymmetry.
      Asymmetric cell division is defined as the generation of two daughter cells with
      different physical content and/or developmental potential. Several organelles and
      cellular components including the centrosome, non-coding RNA, chromatin, and
      recycling endosomes are involved in the process of asymmetric cell division.
      Disruption of this important process is known to induce profound defects in
      development, the immune response, regeneration of tissues, aging, and cancer.
      Here, we discuss recent advances that expand our understanding of the mechanisms
      and consequences of asymmetric cell division in vertebrate organisms.

PMID- 29360276
TI  - Lymph node ratio as a prognostic factor in metastatic cutaneous head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: The prognostic impact of the size and number of nodal metastases in
      head and neck cutaneous squamous cell carcinoma (SCC) is well established. The
      purpose of this study was to validate the prognostic significance of the lymph
      node ratio in metastatic head and neck cutaneous SCC. METHODS: A retrospective
      review of 326 patients with head and neck cutaneous SCC with parotid and/or
      cervical nodal metastases was performed. The primary endpoints were overall
      survival (OS) and disease-free survival (DFS). The minimal-P approach was used to
      investigate the optimal lymph node ratio threshold. RESULTS: Our data included 77
      recurrences and 101 deaths. A lymph node ratio of 6% was a significant predictor
      of shorter DFS (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.11-2.38; P
      = .01) and OS (HR 1.63; 95% CI 1.03-2.58; P = 0.04) on multivariable analysis.
      CONCLUSION: The lymph node ratio is an independent prognosticator of survival
      outcomes in patients presenting with metastatic head and neck cutaneous SCC. A
      lymph node ratio >6% is a significant threshold to categorize patients into low
      and high risk.

PMID- 29360277
TI  - Comparative effectiveness of aerosolized versus oral ribavirin for the treatment
      of respiratory syncytial virus infections: A single-center retrospective cohort
      study and review of the literature.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of viral
      infections in immunocompromised hosts and is associated with significant
      morbidity and mortality. In January 2015, our institution switched from
      aerosolized to oral ribavirin (RBV) for primary treatment of RSV infection among
      high-risk immunocompromised adult patients. The objective of the study was to
      evaluate the clinical and economic outcomes associated with this switch. METHODS:
      Retrospective cohort analysis of adult patients diagnosed with RSV infection and
      treated with RBV between January 1, 2013, and May 31, 2016. RESULTS: Of 46
      patients, 20 (43%) patients received oral RBV and 26 (57%) received aerosolized
      RBV. Underlying conditions included lung transplant (n = 22), hematopoietic cell
      transplant (n = 16), hematological malignancy (n = 5), and structural lung
      diseases (n = 4). At the time of RSV diagnosis, 42 (91%) were hospitalized, 36
      (78%) had clinical and radiographic evidence of lower respiratory tract infection
      (RTI), 9 (20%) were admitted to the ICU, and 4 (9%) required intubation. There
      were no differences in clinical outcomes between the 2 groups with regard to
      adverse events, progression from upper to lower RTI, escalation of care, or 30
      day mortality. Three (15%) in the oral group and 1 (4%) in the aerosolized group
      died within 30 days (P = .33). The cost avoidance attributable to the switch in
      therapy over 1 year is $1.2 million. CONCLUSION: Oral RBV appears to be a safe
      and cost-effective alternative to aerosolized RBV for the management of RSV
      infection in immunocompromised patients. Larger studies are needed to validate
      the safety and efficacy of this approach.

PMID- 29360278
TI  - Outcomes after free tissue transfer for composite oral cavity resections
      involving skin.
AB  - BACKGROUND: Resections involving oral cavity mucosa, bone, and skin present a
      unique challenge. Optimizing outcomes often requires technically demanding
      reconstruction. The purpose of this study is to evaluate outcomes of several
      reconstructive approaches for patients with composite through-and-through
      defects, with a focus on the osteocutaneous radial forearm free flap (RFFF).
      METHODS: We conducted a retrospective evaluation of the cohort of patients
      treated for composite through-and-through defects with cutaneous involvement who
      underwent free flap reconstruction from August 2012 through October 2015.
      RESULTS: Seventeen patients received a single flap (12 cases of osteocutaneous
      RFFF), whereas 10 patients underwent a combination of flaps. Complication rates
      and functional outcomes were favorable in patients who underwent osteocutaneous
      RFFFs. The supraclavicular artery island flap (SCAIF) was used as a second flap
      in 3 cases. CONCLUSION: The osteocutaneous RFFF provides a valuable
      reconstructive option for complex composite resection defects involving skin.
      When 2 flaps are required, the SCAIF is a viable alternative to a second free
      flap or pectoralis flap.

PMID- 29360280
TI  - Dialysis disequilibrium syndrome leading to sudden brain death in a chronic
      hemodialysis patient.
AB  - Dialysis disequilibrium syndrome (DDS) is a rare central nervous system (CNS)
      disease which develops in patients receiving hemodialysis (HD). Although it has
      been reported in patients receiving chronic HD, DDS is more common during or
      immediately after the first HD treatment. The exact incidence of DDS is unknown.
      Death in DDS is an extremely rare phenomenon and to the best of our knowledge
      only 9 cases have been reported showing this association. We present a unique
      case of a 42-year-old female on chronic HD, and no prior history of CNS disease,
      who developed brain death in the setting of DDS 2 hours into the dialysis
      treatment. A literature review of all previously reported cases was performed.

PMID- 29360281
TI  - Ethylene Glycol Electrooxidation Based on Pentangle-Like PtCu Nanocatalysts.
AB  - The research of active and stable electrocatalysts toward liquid-fuel oxidation
      reaction is of great significance for the large-scale commercialization of fuel
      cells. Although extensive efforts have been devoted to pursuing high-performance
      nanocatalysts for fuel cells, both the high cost and sluggish reaction kinetics
      have been two major drawbacks that limited its commercial development. In this
      regard, we demonstrated a facile solvothermal method for the syntheses of an
      advanced class of PtCu nanocatalysts with a unique pentangle-like shape. By
      combining the merits of a highly active surface area as well as the synergistic
      and electronic effects, the as-prepared pentangle-like Pt3 Cu nanocatalysts
      showed superior electrocatalytic activity towards ethylene glycol oxidation with
      a mass and specific activities of 5162.6 mA mg-1 and 9.7 mA cm-2 , approximately
      5.0 and 5.1 times higher than the commercial Pt/C, respectively. More
      significantly, the Pt3 Cu pentangle also showed excellent long-term stability
      with less activity decay and negligible changes in structure after 500 cycles,
      indicating another class of anode catalysts for fuel cells and beyond.

PMID- 29360282
TI  - Left ventricular assist device patient maintained on home hemodialysis: A novel
      class of patients to the home dialysis population.
AB  - Severe heart failure is increasingly being managed by cardiac transplantation,
      and in some cases mechanical support devices serve as destination therapies. Left
      ventricular assist devices (LVADs) were approved for destination therapy for end
      stage heart failure patients before the more advanced total artificial heart
      modality became available. One common complication of mechanical assist device
      placement is acute kidney injury. Historically, patients with mechanical support
      devices have had to have inpatient hemodialysis until combined heart kidney
      transplant. Though, some units have started accepting LVAD patients in outpatient
      dialysis clinics. The cost of in center hemodialysis remains high and home
      dialysis modalities are becoming increasingly popular. We report the first
      patient with an LVAD to undergo training and successful home hemodialysis while
      awaiting combined heart kidney transplantation.

PMID- 29360285
TI  - Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell
      carcinoma: A National Cancer Database study.
AB  - BACKGROUND: Few studies have examined the frequency and survival implications of
      clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC).
      METHODS: Oral cavity SCC cases with full pathologic staging information were
      identified in the National Cancer Database (NCDB). Clinical and pathologic stages
      were compared. Multivariate logistic regressions were performed to identify
      factors associated with stage discrepancy. RESULTS: There were 9110 cases
      identified, of which 67.3% of the cases were stage concordant, 19.9% were
      upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was
      more common than T classification discordance (27.6%). In cases of T
      classification discordance, downstaging is more common than upstaging (15.4% vs
      12.1% of cases), but in cases of N classification discordance, the reverse is
      true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases).
      CONCLUSION: Clinicopathologic stage discrepancy in oral cavity SCC is a common
      phenomenon that is associated with a number of clinical factors and has survival
      implications.

PMID- 29360286
TI  - Radiotherapy-related complications presenting to a urology department: a more
      common problem than previously thought?
AB  - OBJECTIVE: To quantify the burden of the side effects of radiotherapy on a
      tertiary referral urology department. PATIENTS AND METHODS: A prospective study
      of all urology admissions to a public urology department at a tertiary hospital
      in a 6-month period was performed. Patients admitted with complications
      attributable to radiotherapy were included in the study. Data obtained included
      patient demographics, radiotherapy details, complication type and management
      required. RESULTS: A total of 1198 patients were admitted; 921 (77%) were
      elective and 277 (23%) were emergency admissions. Thirteen out of the 921 (1.4%)
      elective admissions and 20 out of the 277 (7.2%) emergency admissions were
      attributable to radiotherapy complications. Radiotherapy complications was the
      fourth most common reason for emergency admission, ahead of acute urinary
      retention. These 33 admissions were accounted for by 21 patients. A total of 39
      separate complications attributable to radiotherapy were diagnosed, with some
      patients having multiple complications. The median (interquartile range) time to
      onset of complications was 4 (1-9) years. The surgical intervention rate was 67%.
      The commonest procedures were washout with/without clot evacuation or diathermy
      in theatre (15.8%) and urethral dilatation/bladder neck incision (15.8%). Two
      urinary diversions and two cystoprostatectomies plus urinary diversion were
      performed. CONCLUSION: Radiotherapy complications are consequential and account
      for a substantial proportion of a tertiary urology department's emergency
      workload. These complications generally occur years after radiotherapy and
      frequently require surgical intervention.

PMID- 29360284
TI  - Amyloid fibril polymorphism: a challenge for molecular imaging and therapy.
AB  - The accumulation of misfolded proteins (MPs), both unique and common, for
      different diseases is central for many chronic degenerative diseases. In certain
      patients, MP accumulation is systemic (e.g. TTR amyloid), and in others, this is
      localized to a specific cell type (e.g. Alzheimer's disease). In
      neurodegenerative diseases, NDs, it is noticeable that the accumulation of MP
      progressively spreads throughout the nervous system. Our main hypothesis of this
      article is that MPs are not only markers but also active carriers of
      pathogenicity. Here, we discuss studies from comprehensive molecular approaches
      aimed at understanding MP conformational variations (polymorphism) and their
      bearing on spreading of MPs, MP toxicity, as well as MP targeting in imaging and
      therapy. Neurodegenerative disease (ND) represents a major and growing societal
      challenge, with millions of people worldwide suffering from Alzheimer's or
      Parkinson's diseases alone. For all NDs, current treatment is palliative without
      addressing the primary cause and is not curative. Over recent years, particularly
      the shape-shifting properties of misfolded proteins and their spreading pathways
      have been intensively researched. The difficulty in addressing ND has prompted
      most major pharma companies to severely downsize their nervous system disorder
      research. Increased academic research is pivotal for filling this void and to
      translate basic research into tools for medical professionals. Recent discoveries
      of targeting drug design against MPs and improved model systems to study
      structure, pathology spreading and toxicity strongly encourage future studies
      along these lines to provide an opportunity for selective imaging, prognostic
      diagnosis and therapy.

PMID- 29360287
TI  - Percutaneous perfusion monitoring for the detection of hemodialysis induced
      cardiovascular injury.
AB  - INTRODUCTION: The safe delivery of hemodialysis (HD) faces dual challenges; the
      accurate detection of systemic circulatory stress producing cardiovascular (CV)
      injury, and the ability to enable effective preemptive intervention for such
      injury. We performed a pilot study to examine the capability of a new
      noninvasive, real-time monitoring system to detect the deleterious effects of HD
      on CV stability. METHODS: Eight patients were evaluated with echocardiography
      prior to the initiation of HD and again at peak HD stress. Continuous CV
      physiologic monitoring was performed throughout using oximeter-based pulse
      waveform analysis (CVInsight(r) Monitoring System, Intelomed, Inc., Warrendale,
      PA, USA). Longitudinal strain (LS) values for 12 left ventricular segments were
      generated using speckle-tracking software (EchoPac, GE), to assess the presence
      of HD-induced regional wall motion abnormalities (RWMA), indicative of myocardial
      stunning. FINDINGS: A reduction in pulse strength (PS) of >=40% detected by CVI
      was associated with the development of RWMA (P = 0.005). This reduction occurred
      in 6/8 patients, all of whom exhibited myocardial stunning. Two patients had no
      significant reduction in PS nor evidence of myocardial stunning. In subjects with
      cardiac stunning, the decrease in PS was evident early during HD, 11.49 +/- 10
      minutes into HD treatment, prior to the detection of RWMA, which were assessed at
      peak HD stress, mean 210 +/- 16.43 minutes into HD treatment. DISCUSSION:
      Percutaneous perfusion monitoring, using pulse wave analysis, appears to be
      useful in identifying circulatory stress during HD and predicting the development
      of HD-induced myocardial stunning with a lead time long enough to consider timely
      intervention.

PMID- 29360288
TI  - Unexpected Falls During Clozapine Treatment Explained by Myoclonus.

PMID- 29360289
TI  - Catatonia as a Manifestation of Cerebral Venous Sinus Thrombosis.

PMID- 29360290
TI  - Facial Emotion Recognition Performance Differentiates Between Behavioral Variant
      Frontotemporal Dementia and Major Depressive Disorder.
AB  - OBJECTIVE: Misdiagnosis of early behavioral variant frontotemporal dementia
      (bvFTD) with major depressive disorder (MDD) is not uncommon due to overlapping
      symptoms. The aim of this study was to improve the discrimination between these
      disorders using a novel facial emotion perception task. METHOD: In this
      prospective cohort study (July 2013-March 2016), we compared 25 patients meeting
      Rascovsky diagnostic criteria for bvFTD, 20 patients meeting DSM-IV criteria for
      MDD, 21 patients meeting McKhann diagnostic criteria for Alzheimer's disease
      dementia, and 31 healthy participants on a novel emotion intensity rating task
      comprising morphed low-intensity facial stimuli. Participants were asked to rate
      the intensity of morphed faces on the congruent basic emotion (eg, rating on
      sadness when sad face is shown) and on the 5 incongruent basic emotions (eg,
      rating on each of the other basic emotions when sad face is shown). RESULTS:
      While bvFTD patients underrated congruent emotions (P < .01), they also overrated
      incongruent emotions (P < .001), resulting in confusion of facial emotions. In
      contrast, MDD patients overrated congruent negative facial emotions (P < .001),
      but not incongruent facial emotions. Accordingly, ratings of congruent and
      incongruent emotions highly discriminated between bvFTD and MDD patients, ranging
      from area under the curve (AUC) = 93% to AUC = 98%. Further, an almost complete
      discrimination (AUC = 99%) was achieved by contrasting the 2 rating types. In
      contrast, Alzheimer's disease dementia patients perceived emotions similarly to
      healthy participants, indicating no impact of cognitive impairment on rating
      scores. CONCLUSIONS: Our congruent and incongruent facial emotion intensity
      rating task allows a detailed assessment of facial emotion perception in patient
      populations. By using this simple task, we achieved an almost complete
      discrimination between bvFTD and MDD, potentially helping improve the diagnostic
      certainty in early bvFTD.

PMID- 29360291
TI  - Prospective Study of Brain Wave Changes Associated With Cranial Electrotherapy
      Stimulation.
AB  - Objective: To explore brain wave changes associated with cranial electrotherapy
      stimulation (CES) among subjects receiving psychiatric care. Methods:
      Quantitative electroencephalogram data were obtained before and after a 20-minute
      session of CES. The investigators recruited active-duty military subjects from
      Walter Reed National Military Medical Center's Psychiatry Continuity Service,
      Bethesda, Maryland. Fifty subjects participated in this prospective, convenience
      sample study from August 2016 through March 2017. The main outcome measures were
      changes in brain wave activity and the Subjective Units of Distress Scale.
      Results: The typical subject was mildly depressed and had severe trauma-related
      symptoms and sleep problems. There was a significant increase (P = .000) in the
      higher beta frequencies (18-21 Hz, 21-33 Hz, and 33-48 Hz) and a strong effect
      (with the Cohen d around 1.5) immediately following the 20-minute CES. Ten
      minutes after CES, slower wave activity (4-8 Hz and 8-12 Hz) significantly
      decreased (P < .05), while higher beta wave activity (13-15 Hz, 18-21 Hz, and 21
      33 Hz) increased. A strong effect (with the Cohen d around 1.5) persisted in the
      beta brain wave bands 18-21 Hz and 21-33 Hz. Conclusions: Brain wave measurements
      taken immediately after the 20-minute CES session showed a significant and strong
      effect in the beta region, suggesting an increase in mental alertness, focus, and
      concentration. Ten minutes after the CES session, an even more marked change in
      brain wave activity occurred. The significant and strong effect in the beta
      region persisted but was joined by a reduction in slower wave activity,
      indicating an increase in mental alertness. Trial Registration:
      ClinicalTrials.gov identifier NCT03298308.

PMID- 29360292
TI  - The Brussels Statement on the Future Needs for Caries Epidemiology and
      Surveillance in Europe.
AB  - Following debate and discussion prompted by a focussed, day long pre-ORCA
      Symposium in July 2015, the Alliance for a Cavity-Free Future Pan-European
      Chapter, the Platform for Better Oral Health in Europe, and the European
      Association of Dental Public Health have agreed this statement on the future
      needs for caries epidemiology and surveillance in Europe. Each organisation
      agreed to support the planned publication of the Statement, and will make it
      available on their Organisation's websites and strive to implement its
      recommendations.

PMID- 29360293
TI  - The relationship between depression and periodontal diseases.
AB  - OBJECTIVE: A cross-sectional study was conducted to investigate whether
      depression is associated with periodontal diseases in a representative sample of
      South Korean adults Methods: We used data from the sixth Korea National Health
      and Nutrition Examination Survey (KNHANES VI), conducted in 2014. We included in
      this study 4328 participants aged over 20 years (1768 males and 2560 females).
      Depression was assessed with the Patient Health Questionnaire (PHQ-9) and history
      of physician-diagnosed depression. Periodontal diseases were assessed a gingival
      bleeding, calculus and periodontal pockets. The data were analyzed using the chi
      square test and multiple logistic regression. RESULTS: People with any
      periodontal diseases tended to be old, male, married, low income, poor education,
      blue-collar occupation, diabetes mellitus, hypertension, overweight, smoking, not
      using dental floss or interdental brush in univariate analysis. Neither self
      reported nor diagnosed depression was associated with the presence of any or
      severe periodontal disease in the total sample. In participants aged 20-29 years
      only, the presence of any periodontal disease was associated with self-reported
      depression (OR, 2.031; 95% CI, 1.011-4.078). In the same age group, the presence
      of severe periodontal disease was associated with both self-reported depression
      (OR, 6.532; 95% CI, 2.190-19.483) and diagnosed depression (OR, 7.729; 95% CI,
      1.966-30.389). CONCLUSION: Self-reported depression was significantly associated
      with the presence of any or severe periodontal disease, and diagnosed depression
      was significantly associated with severe periodontal diseases only in
      participants aged 20-29 years.

PMID- 29360294
TI  - Medical Malpractice and Tort Reform.

PMID- 29360295
TI  - Quality of Healthcare.

PMID- 29360296
TI  - Healthcare Reform: Enforcement And Compliance.

PMID- 29360297
TI  - Healthcare Reform: Administrative Rulemaking.

PMID- 29360298
TI  - Healthcare Reform: Delivery Reform.

PMID- 29360299
TI  - Healthcare Reform: Insurance Market Reform.

PMID- 29360300
TI  - Healthcare Reform: Payment Reform.

PMID- 29360302
TI  - Managed Care.

PMID- 29360301
TI  - Healthcare Reform: State Specific Responses.

PMID- 29360303
TI  - Mandated Benefits.

PMID- 29360304
TI  - Long-Term Care: End-of-Life Issues.

PMID- 29360305
TI  - Long-Term Care: Funding of Long-Term Care.

PMID- 29360306
TI  - Long-Term Care: Facility Quality and Safety.

PMID- 29360307
TI  - Long-Term Care: Home- and Community-Based Services.

PMID- 29360308
TI  - Medicaid Copayments.

PMID- 29360309
TI  - Nanochannel Implants for Minimally-Invasive Insertion and Intratumoral Delivery.
AB  - Novel approaches to achieve local, intratumoral drug delivery have the dual
      benefit of reducing systemic toxicity while enhancing efficacy for malignant
      cells. We have developed a new implantable system combining a next-generation
      BioNEMS nanofluidic membrane with parallel nanochannels that offers controlled
      release of biomolecules. Based on concentration-driven diffusive transport,
      nanochannel membranes provide a "drug agnostic" delivery mechanism. Integrating
      this nanotechnology within a small implantable capsule permits multipurpose
      functionality and compatibility with different therapeutic approaches as well as
      diagnostic imaging capability. A minimally-invasive, percutaneous trocar delivery
      mechanism enables serial implantation throughout a target tissue volume. In this
      manuscript, we demonstrate that this platform is capable of sustained delivery
      for chemotherapy, radiosensitization, immunomodulation, and imaging contrast,
      among others. This platform's utility was established through release of
      doxorubicin, OX86, FGK45, and Magnevist. Further proof-of-concept experiments
      demonstrated successful in vivo implantation and intratumoral release of
      antibodies and contrast agents, as well as the platform's MR-compatibility and
      capability as a radiopaque fiducial. These results provide strong evidence for a
      flexible, multifunctional nanofluidic implant capable of broadening local
      delivery utility in the clinic.

PMID- 29360310
TI  - Medicaid Provider Tax.

PMID- 29360311
TI  - Benefits and Services.

PMID- 29360333
TI  - Affordable Care Act Expansion.

PMID- 29360334
TI  - Construction of 3-D Cellular Multi-Layers with Extracellular Matrix Assembly
      Using Magnetic Nanoparticles.
AB  - Construction of 3-dimensional (3-D) engineered tissue is increasingly being
      investigated for use in drug discovery and regenerative medicine. Here, we
      developed multi-layered 3-D cellular assembly by using magnetic nanoparticles
      (MNP) isolated from Magnetospirillum sp. AMB-1 magnetotactic bacteria. Magnetized
      human dermal fibroblasts (HDFBs) were prepared by treatment with the MNP, induced
      to form 3-D assembly under a magnetic field. Analyses including LIVE/DEAD assay,
      transmission electron microscopy revealed that the MNP were internalized via
      clathrin-mediated endocytosis without cytotoxicity. The magnetized HDFBs could
      build 3-D structure as a function of seeding density. When the highest seeding
      density (5 * 105 cells/mm2 was used, the thickness of assembly was 41.90 +/- 1.69
      MUm, with approximately 9.3 +/- 1.6 cell layers being formed. Immunofluorescence
      staining confirmed homogeneous distribution of ECM and junction proteins
      throughout the 3-D assembly. Real-time PCR analysis showed decrease in expression
      levels of collagen types I and IV but increase in that of connexin 43 in the 3-D
      assembly compared with the 2-D culture. Finally, we demonstrated that the
      discernible layers can be formed hierarchically by serial assembly. In
      conclusion, our study showed that a multi-layered structure can be easily
      prepared using magnetically-assisted cellular assembly with highlighting cell
      cell and cell-ECM communication.

PMID- 29360335
TI  - Federal Medicaid Policy.

PMID- 29360336
TI  - Plasmon Resonant Silica-Coated Silver Nanoplates as Contrast agents for Optical
      Coherence Tomography.
AB  - Silica-coated silver nanostructures are identified as potential contrast agents
      for visible and near-infrared bio-imaging applications due to their high optical
      extinction caused by localized surface plasmon resonance (LSPR), improved
      chemical stability, and lower toxicity. We demonstrate the potential of plasmon
      resonant silica-coated silver nanoplates as a contrast agent for optical
      coherence tomography (OCT). It is shown that, triangular-shaped silica-coated
      silver nanoplates (SSNPs) with a side length of 170 +/- 5 nm, base silver
      thickness of 10 +/- 1 nm, and silica shell thickness of 40 +/- 2 nm, exhibit
      higher optical extinction at a 1300 nm wavelength range, thus making them an
      excellent contrast agent for OCT imaging. Optical extinction characterization
      using OCT is found to be reasonably consistent with ultraviolet (UV)-Vis-near
      infrared (NIR) spectroscopy and finite difference time-domain (FDTD)-based
      analysis. Ex vivo studies on pig adipose tissue demonstrate that LSPR-induced
      enhanced scattering in SSNPs contributes to the OCT signal, leading to images
      with better contrast. Moreover, average A-scan profiles acquired at different
      time delays show the downward propagation of SSNPs and the extension of signal
      enhancement at the deeper regions. Speckle variance OCT images show that SSNPs
      are efficiently distributed over the targeted tissue region, demonstrating their
      applicability in a large lesion area.

PMID- 29360337
TI  - Surface-Enhanced Raman Scattering and Fluorescence-Based Dual Nanoprobes for
      Multiplexed Detection of Bacterial Pathogens.
AB  - Surface-enhanced Raman scattering (SERS)-based biosensing has been of growing
      interest for the detection of bacterial pathogens. Moreover, fluorescence (FL)
      based bioimaging is also useful in that it is rapid, nearly non-destructive and
      has high sensitivity. In this study, for the first time, we report the
      preparation of dual nanoprobes based on both SERS and FL. These probes comprise
      hierarchical nanostructures with metallic nanoparticle clusters (MNPCs). In
      combination with magnetic beads (MBs), the probes were used for fast and
      multiplexed detection of bacterial pathogens. Both MNPCs with different Raman
      dyes and two sets of FL dyes were simultaneously encapsulated within polymeric
      nanoparticles using electrohydrodynamic (EHD) jetting and chemically stabilized.
      Two different sets of monoclonal antibodies (mAbs) against two kinds of bacterial
      pathogens, Escherichia coli and Francisella tularensis, were separately
      conjugated with the dual nanoprobes and the MBs. Sandwich-type immunocomplexes
      composed of SERS-FL dual nanoprobes, pathogens, and MBs were formed in the
      presence of E. coli and F. tularensis, and a linear correlation was observed
      between Raman intensity and pathogen concentration in the range of 102-106
      cells/mL; the limit of detection was less than 102 cells/mL. Also, selective
      sandwich-type immunocomplexes against the pathogens were successfully imaged by
      FL signals at 514 nm and 633 nm wavelength for excitation. In conclusion,
      excellent capability of fast imaging and multiplexed detection of bacterial
      pathogens was achieved using a new class of SERS-FL dual nanoprobes, providing a
      powerful tool for qualitative and quantitative multiplexed biodetection of
      pathogens.

PMID- 29360338
TI  - Liposome-Protamine-DNA Nanoparticle-Mediated Delivery of Short Hairpin RNA
      Targeting Brachyury Inhibits Chordoma Cell Growth.
AB  - Recent evidence suggests that brachyury is a crucial molecular driver in the
      initiation and propagation of chordoma. However, no small molecules have been
      used to specifically target brachyury. Short hairpin RNA (shRNA) has therapeutic
      promise for the genetic treatment of cancer, but the usage of shRNA therapeutics
      is limited by obstacles related to effective delivery into the nuclei of target
      cancer cells due to their inherent sensitivity to nucleases and large polyanionic
      characteristics. To overcome instability and low transfection efficiency,
      liposome-protamine-DNA (LPD) nanoparticles were synthesized and investigated as a
      non-viral carrier of shRNA targeting brachyury in chordoma cells. The size, zeta
      potential, affinity and transfection efficiency of LPD-shRNA complexes were
      characterized, and their biological functions in chordoma cells were evaluated.
      The transfection efficiency of LPD-shRNA was significant higher than naked shRNA.
      LPD delivered brachyury shRNA into chordoma cells and inhibited brachyury
      expression, induced apoptosis, upregulated the epithelial biomarker, E-cadherin,
      downregulated the mesenchymal biomarker, Snail and Slug, and suppressed cell
      growth. These data indicate that LPD might be a promising non-viral carrier for
      shRNA in gene targeted therapy of chordoma.

PMID- 29360339
TI  - Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous
      Penetration Studied by Multimodal Imaging.
AB  - Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core
      multimodal probe for imaging and their penetration into human skin biopsies was
      studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The
      penetration was shown to be dependent on the molecular weight of the molecule and
      limited to the upper layer of the skin.

PMID- 29360340
TI  - Thermally Activated Delayed Fluorescence Pendant Copolymers with Electron- and
      Hole-Transporting Spacers.
AB  - To study the effect of hole- and electron-transporting spacers in copolymers on
      the thermally activated delayed fluorescence (TADF) properties and device
      efficiency of copolymers, two series of copolymers PCzPT-x and POPT-x have been
      designed and synthesized successfully. In these copolymers, 2-(10H-phenothiazin
      10-yl)dibenzothiophene-S,S-dioxide units give green-yellow TADF, while hole
      transporting 9-(4-vinylphenyl)-9H-carbazole units or electron-transporting
      diphenyl(4-vinylphenyl)phosphine oxide act as spacers or hosts. Their thermal,
      electrochemical, photophysical, and electroluminescent properties and theoretical
      calculations are systematically investigated to illustrate the relationships
      between molecular structures and photophysical properties. By optimizing the
      upconversion and radiative decay rate and managing the energy transfer, a green
      yellow device based on POPT-25 achieves a maximum external quantum efficiency of
      5.2%, a current efficiency of 16.8 cd/A, and a power efficiency of 7.8 lm/W with
      CIE coordinates of (0.36, 0.50). Moreover, an external quantum efficiency of 3.5%
      at the practical luminescence of 100 cd/m2 is obtained.

PMID- 29360341
TI  - Fixed-Charge Trimethyl Pyrilium Modification for Enabling Enhanced Top-Down Mass
      Spectrometry Sequencing of Intact Protein Complexes.
AB  - Mass spectrometry of intact proteins and protein complexes has the potential to
      provide a transformative level of information on biological systems, ranging from
      sequence and post-translational modification analysis to the structures of whole
      protein assemblies. This ambitious goal requires the efficient fragmentation of
      both intact proteins and the macromolecular, multicomponent machines they
      collaborate to create through noncovalent interactions. Improving technologies in
      an effort to achieve such fragmentation remains perhaps the greatest challenge
      facing current efforts to comprehensively analyze cellular protein composition
      and is essential to realizing the full potential of proteomics. In this work, we
      describe the use of a trimethyl pyrylium (TMP) fixed-charge covalent labeling
      strategy aimed at enhancing fragmentation for challenging intact proteins and
      intact protein complexes. Combining analysis of TMP-modified and unmodified
      protein complexes results in a greater diversity of regions within the protein
      that give rise to fragments, and results in an up to 2.5-fold increase in
      sequence coverage when compared to unmodified protein alone, for protein
      complexes up to 148 kDa. TMP modification offers a simple and powerful platform
      to expand the capabilities of existing mass spectrometric instrumentation for the
      complete characterization of intact protein assemblies.

PMID- 29360342
TI  - Matrix Metalloproteinase-9-Responsive Nanogels for Proximal Surface Conversion
      and Activated Cellular Uptake.
AB  - Here, we have exploited the heightened extracellular concentration of matrix
      metalloproteinase-9 (MMP-9) to induce surface-conversional properties of nanogels
      with the aim of tumor-specific enhanced cellular uptake. A modular polymeric
      nanogel platform was designed and synthesized for facile formulation and
      validation of MMP-9-mediated dePEGylation and generation of polyamine-type
      surface characteristics through peptide N-termini. Nanogels containing MMP-9
      cleavable motifs and different poly(ethylene glycol) corona lengths (350 and 750
      g/mol) were prepared, and enzymatic surface conversional properties were
      validated by MALDI characterization of cleaved byproducts, fluorescamine assay
      amine quantification, and zeta potential. The nanogel with a shorter PEG length,
      mPEG350-NG, exhibited superior surface conversion in response to extracellular
      concentrations of MMP-9 compared to that of the longer PEG length, mPEG750-NG.
      Confocal microscopy images of HeLa cells incubated with both fluorescein-labeled
      nanogels and DiI-encapsulated nanogels demonstrated greater uptake following MMP
      9 "activation" for mPEG350-NG compared to its nontreated "passive" mPEG350-NG
      parent, demonstrating the versatility of such systems to achieve stimuli
      responsive uptake in response to cancer-relevant proteases.

PMID- 29360344
TI  - Biosynthesis and Characterization of Polyhydroxyalkanoates with Controlled
      Composition and Microstructure.
AB  - Volatile fatty acids (VFA) C2:0 to C6:0 were used as the sole carbon source for
      poly(3-hydroxybutyrate- co-3-hydroxyvalerate) (PHBV) production with controllable
      composition and microstructure in Haloferax mediterranei. Feeding carbon-even VFA
      gave >90 mol % poly(3-hydroxybutyrate) (3HB) PHBV, while carbon-odd VFA generated
      >87 mol % poly(3-hydroxyvalerate) (3HV) PHBV. Bespoke random, block, and blend
      copolymers with 0-100 mol % 3HV were synthesized using C4:0/C5:0 mixtures. The
      copolymer 3HV fraction is proportional to the %C5:0 in the feed mixture, allowing
      control over copolymer composition. Microstructure depends on the substrate
      addition order: cofeeding generated random copolymers, while sequential feeding
      created block and blend copolymers. On average, the PHBV had an ultrahigh
      molecular weight of 3 * 106 g/mol. 3HV rich copolymers showed lower melting
      temperatures, enhanced elasticity, and ductility. H. mediterranei is ideal for
      large-scale production of PHBV due to its inherent bioprocessing advantages,
      while control over the composition and microstructure of PHBV will facilitate the
      production of biopolymers capable of meeting industrial criteria for specific
      applications.

PMID- 29360343
TI  - Site-Specific Incorporation of a Thioester Containing Amino Acid into Proteins.
AB  - Here, we report the site-specific incorporation of a thioester containing
      noncanonical amino acid (ncAA) into recombinantly expressed proteins.
      Specifically, we genetically encoded a thioester-activated aspartic acid (ThioD)
      in bacteria in good yield and with high fidelity using an orthogonal nonsense
      suppressor tRNA/aminoacyl-tRNA synthetase (aaRS) pair. To demonstrate the utility
      of ThioD, we used native chemical ligation to label green fluorescent protein
      with a fluorophore in good yield.

PMID- 29360345
TI  - Heme Binding to Porphobilinogen Deaminase from Vibrio cholerae Decelerates the
      Formation of 1-Hydroxymethylbilane.
AB  - Porphobilinogen deaminase (PBGD) is an enzyme that catalyzes the formation of
      hydroxymethylbilane, a tetrapyrrole intermediate, during heme biosynthesis
      through the stepwise polymerization of four molecules of porphobilinogen. PBGD
      from Vibrio cholerae was expressed in Escherichia coli and characterized in this
      study. Unexpectedly, spectroscopic measurements revealed that PBGD bound one
      equivalent of heme with a dissociation constant of 0.33 +/- 0.01 MUM. The
      absorption and resonance Raman spectra suggested that heme is a mixture of the 5
      coordinate and 6-coordinate hemes. Mutational studies indicated that the 5
      coordinate heme possessed Cys105 as a heme axial ligand, and His227 was
      coordinated to form the 6-coordinate heme. Upon heme binding, the deamination
      activity decreased by approximately 15%. The crystal structure of PBGD revealed
      that His227 was located near Cys105, but the side chain of His227 did not point
      toward Cys105. The addition of the cyanide ion to heme-PBGD abolished the effect
      of heme binding on the enzymatic activity. Therefore, coordination of His227 to
      heme appeared to induce reorientation of the domains containing Cys105, leading
      to a decrease in the enzymatic activity. This is the first report indicating that
      the PBGD activity is controlled by heme, the final product of heme biosynthesis.
      This finding improves our understanding of the mechanism by which heme
      biosynthesis is regulated.

PMID- 29360346
TI  - Kinetic and Conformational Insights into Islet Amyloid Polypeptide Self-Assembly
      Using a Biarsenical Fluorogenic Probe.
AB  - Amyloid fibril formation and tissue deposition are associated with many diseases.
      Studies have shown that prefibrillar intermediates, such as oligomers, are the
      most toxic proteospecies of the amyloidogenic cascade. Thus, understanding the
      mechanisms of formation and the conformational ensemble of prefibrillar species
      is critical. Due to their transient and heterogeneous nature, detection and
      characterization of prefibrillar species remain challenging. The fluorogenic
      probe fluorescein arsenical hairpin (FlAsH), which recognizes a tetracysteine
      motif, has been recently used to detect the oligomerization of amyloidogenic
      peptides encompassing a Cys-Cys tag. In this study, we extended the FlAsH
      detection method to gain novel kinetic and conformational insights into the self
      assembly of islet amyloid polypeptide (IAPP), a 37-residue peptide hormone whose
      deposition is associated with type II diabetes. By positional scanning of the Cys
      Cys motif, the stability of the noncontiguous tetracysteine FlAsH-binding sites
      formed during self-assembly was evaluated and revealed rapid monomer self
      recognition through the convergence of C-terminal domains. On the other hand, the
      N-terminal domains come close to each other only upon the formation of the cross
      beta-sheet amyloid structure. We demonstrated that this method is well-suited to
      detect thioflavin T-negative fibrils and to screen inhibitors of amyloid
      formation. This study highlights that with positional scanning of the split
      tetracysteine motif (Cys-Cys), the FlAsH detection method offers unique time
      dependent conformational insights on the proteospecies assembled throughout the
      amyloidogenic pathway.

PMID- 29360347
TI  - Large Dendritic Monolayer MoS2 Grown by Atmospheric Pressure Chemical Vapor
      Deposition for Electrocatalysis.
AB  - The edge sites of MoS2 are catalytically active for the hydrogen evolution
      reaction (HER), and growing monolayer structures that are edge-rich is desirable.
      Here, we show the production of large-area highly branched MoS2 dendrites on
      amorphous SiO2/Si substrates using an atmospheric pressure chemical vapor
      deposition and explore their use in electrocatalysis. By tailoring the substrate
      construction, the monolayer MoS2 evolves from triangular to dendritic morphology
      because of the change of growth conditions. The rough edges endow dendritic MoS2
      with a fractal dimension down to 1.54. The highly crystalline basal plane and the
      edge of the dendrites are visualized at atomic resolution using an annular dark
      field scanning transmission electron microscope. The monolayer dendrites exhibit
      strong photoluminescence, which is indicative of the direct band gap emission,
      which is preserved after being transferred. Post-transfer sulfur annealing
      restores the structural defects and decreases the n-type doping in MoS2
      monolayers. The annealed MoS2 dendrites show good and highly durable HER
      performance on the glassy carbon with a large exchange current density of 32 MUA
      cmgeo-2, demonstrating its viability as an efficient HER catalyst.

PMID- 29360348
TI  - Engineering Erg10 Thiolase from Saccharomyces cerevisiae as a Synthetic Toolkit
      for the Production of Branched-Chain Alcohols.
AB  - Thiolases catalyze the condensation of acyl-CoA thioesters through the Claisen
      condensation reaction. The best described enzymes usually yield linear
      condensation products. Using a combined computational/experimental approach, and
      guided by structural information, we have studied the potential of thiolases to
      synthesize branched compounds. We have identified a bulky residue located at the
      active site that blocks proper accommodation of substrates longer than acetyl
      CoA. Amino acid replacements at such a position exert effects on the activity and
      product selectivity of the enzymes that are highly dependent on a protein
      scaffold. Among the set of five thiolases studied, Erg10 thiolase from
      Saccharomyces cerevisiae showed no acetyl-CoA/butyryl-CoA branched condensation
      activity, but variants at position F293 resulted the most active and selective
      biocatalysts for this reaction. This is the first time that a thiolase has been
      engineered to synthesize branched compounds. These novel enzymes enrich the
      toolbox of combinatorial (bio)chemistry, paving the way for manufacturing a
      variety of alpha-substituted synthons. As a proof of concept, we have engineered
      Clostridium's 1-butanol pathway to obtain 2-ethyl-1-butanol, an alcohol that is
      interesting as a branched model compound.

PMID- 29360349
TI  - Realizing Large-Scale, Electronic-Grade Two-Dimensional Semiconductors.
AB  - Atomically thin transition metal dichalcogenides (TMDs) are of interest for next
      generation electronics and optoelectronics. Here, we demonstrate device-ready
      synthetic tungsten diselenide (WSe2) via metal-organic chemical vapor deposition
      and provide key insights into the phenomena that control the properties of large
      area, epitaxial TMDs. When epitaxy is achieved, the sapphire surface
      reconstructs, leading to strong 2D/3D (i.e., TMD/substrate) interactions that
      impact carrier transport. Furthermore, we demonstrate that substrate step edges
      are a major source of carrier doping and scattering. Even with 2D/3D coupling,
      transistors utilizing transfer-free epitaxial WSe2/sapphire exhibit ambipolar
      behavior with excellent on/off ratios (~107), high current density (1-10 MUA.MUm
      1), and good field-effect transistor mobility (~30 cm2.V-1.s-1) at room
      temperature. This work establishes that realization of electronic-grade epitaxial
      TMDs must consider the impact of the TMD precursors, substrate, and the 2D/3D
      interface as leading factors in electronic performance.

PMID- 29360350
TI  - Arresting "Loose Bolt" Internal Conversion from -B(OH)2 Groups is the Mechanism
      for Emission Turn-On in ortho-Aminomethylphenylboronic Acid-Based Saccharide
      Sensors.
AB  - Different mechanisms for the emission turn-on of ortho-aminomethylphenylboronic
      acids with appended fluorophores in response to saccharide binding in aqueous
      media have been postulated, such as photoinduced electron transfer (PET), "pKa
      switch", and disaggregation. However, none of the hypotheses is consistent with
      all the data for boronic acid-based sensors. To create a unifying theory that can
      explain the data, we performed a series of experiments to explore the origin of
      the emission turn-on with several boronic-acid based sensors upon binding
      fructose. First, we showed that the receptors and their complexes with fructose
      are solvent-inserted, with no B-N interactions. Second, we verified that the
      sensors are not aggregated. Third, in pure methanol, that exchanges -B(OH)2 to 
      B(OMe)2 groups, we found no fluorescence response upon binding fructose. We
      propose this occurs via lessening of internal conversion mechanisms. To
      investigate this proposal further, we performed a solvent isotope effect study.
      The fluorescence of the probes in D2O (-B(OH)2 -> -B(OD)2) does not change upon
      fructose binding. It is well accepted that -OD oscillators are less efficient
      energy acceptors due to their lower frequency vibrational modes. Thus, our
      studies reveal that modulating the -B(OH)2-induced internal conversion (an
      example of a "loose bolt effect") explains how potentially all ortho
      aminomethylphenylboronic acid-based fluorescence sensors signal the presence of
      sugars.

PMID- 29360351
TI  - Weak Hydrogen Bonds Lead to Self-Healable and Bioadhesive Hybrid Polymeric
      Hydrogels with Mineralization-Active Functions.
AB  - Hydrogels with self-healing features that can spontaneously repair themselves
      upon mechanical damage are increasingly attractive for biomedical applications.
      Many attempts have been made to develop unique hydrogels possessing this
      property, as well as stimuli-responsiveness and biocompatibility; however, the
      hydrogel fabrication strategies often involve specific design of functional
      monomers that are able to optimally provide reversible physical or chemical
      interactions. Here, we report that weak hydrogen bonds, provided by
      oligo(ethylene glycol) methacrylate (OEGMA) and methacrylic acid (MAA), a monomer
      combination that is commonly used to prepare chemically cross-linking hydrogels,
      can generate self-healable hydrogels with mechanically resilient and adhesive
      properties through a facile one-step free radical copolymerization. The hydrogen
      bonds break and reform, providing an effective energy dissipation mechanism and
      synergic mechanical reinforcement. The physical properties can be simply tuned by
      OEGMA/MAA ratio control and reversible pH adjustment. Furthermore, the hydrogel
      can serve as a robust template for biomineralization to produce hydrogel
      composite that facilitate cell attachment and proliferations. This work is
      synthetically simple and dramatically increases the choice of amendable and
      adhesive hydrogels for industrial and biomedical applications.

PMID- 29360352
TI  - Substituent Effects at the beta-Positions of the Nonfused Pyrroles in a Quadruply
      Fused Porphyrin on the Structure and Optical and Electrochemical Properties.
AB  - We have synthesized 2, a derivative of zinc(II) quadruply fused porphyrinato
      (ZnIIQFP) that is tetrabrominated at the beta-positions of the two nonfused
      pyrroles, by treatment of ZnIIQFP with N-bromosuccinimide. X-ray diffraction
      analysis of a single crystal obtained from a THF solution of 2 by vapor diffusion
      of ethanol (EtOH) revealed that 2 formed an unprecedented dimeric structure, (2)2
      L (L = EtOH), in which one of the brominated QFP ligands acts as a bridging
      ligand in an unprecedented MU-eta3:eta1 coordination mode. In the dimeric
      structure, the two QFP ligands showed a unique eta3 coordination mode for both
      ZnII centers. In (2)2-EtOH, one of the pyrrolic nitrogen atoms of the two
      nonfused pyrroles dissociates from the ZnII center, and the dissociated pyrrolic
      nitrogen atom coordinates to the ZnII center of the other molecule in the dimer.
      The ZnII center having the MU-eta3:eta1-QFP ligand is coordinated by an EtOH
      molecule, and the other ZnII center is coordinated by the eta3-QFP ligand and one
      nitrogen atom of the bridging QFP ligand. The dimeric structure is stable and
      maintained even in a solution of noncoordinating solvents such as
      dichloromethane. The bromo groups of 2 can be substituted with phenyl groups
      under Suzuki coupling conditions to afford the tetraphenyl derivative, 3.
      Furthermore, the effects of the substituents at the beta-positions on the optical
      and electrochemical properties and Lewis acidity of the ZnII centers have been
      investigated. The redox potentials were positively shifted by introduction of
      electron-withdrawing groups at the beta-positions, and the shift widths exhibited
      a linear correlation to the Hammett parameters of the substituents.

PMID- 29360353
TI  - Diastereomerically Differentiated Excited State Behavior in Ruthenium(II)
      Hexafluoroacetylacetonate Complexes of Diphenyl Thioindigo Diimine.
AB  - Mono- and diruthenium hexafluoroacetylacetonate (hfac) complexes of the
      thioindigo-N,N'-diphenyldiimine chelating ligand 3 have been prepared. The
      thioindigo diimine ligand binds to ruthenium in a bidentate fashion in the
      mononuclear compound 2 and serves as a bidentate chelating bridging ligand in the
      diruthenium complexes 1a and 1b. Compound 2 was isolated as a racemic mixture
      while the diruthenium complexes were isolated as the meso (DeltaLambda) 1a and
      rac (DeltaDelta and LambdaLambda) 1b diastereomers. In-depth structural
      characterization of the compounds was performed, including X-ray crystallography,
      1H, 13C, and 19F nuclear magnetic resonance (NMR) spectroscopy, and 2D NMR
      correlation experiments. Electrochemical properties were evaluated utilizing
      cyclic voltammetry. Ground state optical properties of the complexes were
      examined using UV-visible spectroscopy and spectroelectrochemistry. The excited
      state dynamics of the series were investigated by ultrafast transient absorption
      spectroscopy. Variable temperature NMR experiments demonstrated that the rac
      diruthenium compound 1b undergoes conformational exchange with a rate constant of
      8700 s-1 at 298 K, a behavior that is not observed in the meso diastereomer 1a.
      The series of complexes possess metal-to-ligand charge transfer (MLCT) absorption
      bands in the near-infrared (lambdamax 689-783 nm). The compounds do not display
      photoluminescence in room temperature solution-phase experiments or in
      experiments at 77 K. Transient absorption spectroscopy measurements revealed
      excited states with picosecond lifetimes for 1a, 1b, and 2, and
      spectroelectrochemical experiments confirmed assignment of the transient species
      as arising from MLCT transitions. Unexpectedly, the transient absorption
      measurements revealed disparate time constants for the excited state decay of
      diastereomers 1a and 1b.

PMID- 29360354
TI  - Insecticide Resistance Signals Negative Consequences of Widespread Neonicotinoid
      Use on Multiple Field Crops in the U.S. Cotton Belt.
AB  - The intensification of industrial agriculture has been enabled by improved crop
      varieties, genetically engineered crops, fertilizers, and pesticides. Over the
      past 15 years, neonicotinoid seed treatments have been adopted worldwide and are
      used on a large proportion of U.S. field crops. Although neonicotinoids are used
      widely, little is known about how large-scale deployment affects pest populations
      over long periods. Here, we report a positive relationship between the deployment
      of neonicotinoid seed-dressings on multiple crops and the emergence of
      insecticide resistance in tobacco thrips (Frankliniella fusca), a polyphagous
      insect herbivore that is an important pest of seedling cotton but not soybean or
      maize. Using a geospatial approach, we studied the relationship between
      neonicotinoid resistance measured in 301 F. fusca populations to landscape-scale
      crop production patterns across nine states in the southeastern U.S. cotton
      production region, in which soybean, maize and cotton are the dominant crops. Our
      research linked the spatiotemporal abundance of cotton and soybean production to
      neonicotinoid resistance in F. fusca that is leading to a dramatic increase in
      insecticide use in cotton. Results demonstrate that cross-crop resistance
      selection has important effects on pests and, in turn, drives pesticide use and
      increases environmental impacts associated with their use.

PMID- 29360355
TI  - Enantioselective alpha-Benzoyloxylation of beta-Keto Esters by N-Oxide Phase
      Transfer Catalysts.
AB  - An efficient and enantioselective alpha-benzoyloxylation of beta-keto esters has
      been achieved by phase-transfer catalysis. This simple catalytic procedure is
      applicable to a range of beta-keto esters with cinchona-derived N-oxide
      asymmetric phase-transfer catalysts and gives the corresponding products in good
      enantiopurity (up to 95% ee) and yield (up to 99%). This simple and effective
      oxyfunctionalization is a useful synthetic strategy for introducing an oxygen
      containing functional group at the alpha position of beta-dicarbonyl compounds.

PMID- 29360356
TI  - Fluorescent Carbon Dots Derived from Maillard Reaction Products: Their
      Properties, Biodistribution, Cytotoxicity, and Antioxidant Activity.
AB  - Food-borne nanoparticles have received great attention because of their unique
      physicochemical properties and potential health risk. In this study, carbon dots
      (CDs) formed during one of the most important chemical reactions in the food
      processing field, the Maillard reaction from the model system including glucose
      and lysine, were investigated. The CDs purified from Maillard reaction products
      emitted a strong blue fluorescence under ultraviolet light with a fluorescent
      quantum yield of 16.30%. In addition, they were roughly spherical, with sizes of
      around 4.3 nm, and mainly composed of carbon, oxygen, hydrogen, and nitrogen.
      Their surface groups such as hydroxyl, amino, and carboxyl groups were found to
      possibly enable CDs to scavenge DPPH and hydroxyl radicals. Furthermore, the
      cytotoxicity assessment of CDs showed that they could readily enter HepG2 cells
      while causing negligible cell death at low concentration. However, high CDs
      concentrations were highly cytotoxic and led to cell death via interference of
      the glycolytic pathway.

PMID- 29360357
TI  - Origin of pi-Facial Stereoselectivity in Thiophene 1-Oxide Cycloadditions.
AB  - We report a DFT computational study (M06-2X) of pi-facial selectivity in the
      Diels-Alder reactions of thiophene 1-oxide. The preference for the syn
      cycloaddition arises because the ground state geometry of thiophene 1-oxide is
      predistorted into an envelope conformation that resembles the syn transition
      state geometry. The syn distortion occurs to minimize the effect of
      hyperconjugative antiaromaticity in the thiophene 1-oxide, arising from overlap
      of the sigma*SO with the pi-system. The syn selectivity follows through to the
      product structure that is stabilized by a pi-sigma*SO interaction, related to the
      7-norbornenyl ion stability.

PMID- 29360358
TI  - Design, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based
      Hydroxamates for the Treatment of Hepatocellular Carcinoma.
AB  - Class I histone deacetylases (HDACs) are highly expressed and/or upregulated in
      hepatocellular carcinoma (HCC) and are associated with aggressiveness, spread,
      and increased mortality of HCC. Activation of phosphatidylinositol 3-kinase-Akt
      mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway was involved in
      the development of HCC and acquired resistance to sorafenib. A series of purine
      or 5H-pyrrolo[3,2-d]pyrimidine based hydroxamates were designed and developed as
      multitarget drugs to modulate both HDACs and the PI3K/Akt/mTOR pathway. Among 39
      cell lines screened, the molecules (e.g., 20e, 20f, and 20q) were the most
      selective against leukemia, lymphoma, and HCC cells; they also demonstrated
      target modulation in cancer cell lines and in mice bearing MV4-11 and HepG2
      tumors. Compound 20f in particular showed significant single agent oral efficacy
      in hypervascular liver cancer models (e.g., HepG2, HuH-7, and Hep3B) and was well
      tolerated. These encouraging results, along with its favorable target profile and
      tissue distribution, warrant further development of 20f.

PMID- 29360359
TI  - Quadratic String Method for Locating Instantons in Tunneling Splitting
      Calculations.
AB  - The ring-polymer instanton (RPI) method is an efficient technique for calculating
      approximate tunneling splittings in high-dimensional molecular systems. In the
      RPI method, tunneling splitting is evaluated from the properties of the minimum
      action path (MAP) connecting the symmetric wells, whereby the extensive sampling
      of the full potential energy surface of the exact quantum-dynamics methods is
      avoided. Nevertheless, the search for the MAP is usually the most time-consuming
      step in the standard numerical procedures. Recently, nudged elastic band (NEB)
      and string methods, originaly developed for locating minimum energy paths (MEPs),
      were adapted for the purpose of MAP finding with great efficiency gains [ J.
      Chem. Theory Comput. 2016 , 12 , 787 ]. In this work, we develop a new quadratic
      string method for locating instantons. The Euclidean action is minimized by
      propagating the initial guess (a path connecting two wells) over the quadratic
      potential energy surface approximated by means of updated Hessians. This allows
      the algorithm to take many minimization steps between the potential/gradient
      calls with further reductions in the computational effort, exploiting the
      smoothness of potential energy surface. The approach is general, as it uses
      Cartesian coordinates, and widely applicable, with computational effort of
      finding the instanton usually lower than that of determining the MEP. It can be
      combined with expensive potential energy surfaces or on-the-fly electronic
      structure methods to explore a wide variety of molecular systems.

PMID- 29360360
TI  - Benchmark ab Initio Characterization of the Complex Potential Energy Surfaces of
      the X- + NH2Y [X, Y = F, Cl, Br, I] Reactions.
AB  - We report a comprehensive high-level explicitly correlated ab initio study on the
      X- + NH2Y [X,Y = F, Cl, Br, I] reactions characterizing the stationary points of
      the SN2 (Y- + NH2X) and proton-transfer (HX + NHY-) pathways as well as the
      reaction enthalpies of various endothermic additional product channels such as H-
      + NHXY, XY- + NH2, XY + NH2-, and XHY- + NH. Benchmark structures and harmonic
      vibrational frequencies are obtained at the CCSD(T)-F12b/aug-cc-pVTZ(-PP) level
      of theory, followed by CCSD(T)-F12b/aug-cc-pVnZ(-PP) [n = Q and 5] and core
      correlation energy computations. In the entrance and exit channels we find two
      equivalent hydrogen-bonded C1 minima, X-...HH'NY and X-...H'HNY connected by a Cs
      first-order saddle point, X-...H2NY, as well as a halogen-bonded front-side
      complex, X-...YNH2. SN2 reactions can proceed via back-side attack Walden
      inversion and front-side attack retention pathways characterized by first-order
      saddle points, submerged [X-NH2-Y]- and high-energy [H2NXY]-, respectively.
      Product-like stationary points below the HX + NHY- asymptotes are involved in the
      proton-transfer processes.

PMID- 29360361
TI  - Nitroxoline Molecule: Planar or Not? A Story of Battle between pi-pi Conjugation
      and Interatomic Repulsion.
AB  - The conformational properties of the nitro group in nitroxoline (8-hydroxy-5
      nitroquinoline, NXN) were investigated in the gas phase by means of gas electron
      diffraction (GED) and quantum chemical calculations, and also with solid-state
      analysis performed using terahertz time-domain spectroscopy (THz-TDS). The
      results of the GED refinement show that in the equilibrium structure the NO2
      group is twisted by angle phi = 8 +/- 3 degrees  with respect to the 8
      hydroxyoquinoline plane. This is the result of interatomic repulsion of oxygen in
      the NO2 group from the closest hydrogen, which overcomes the energy gain from the
      pi-pi conjugation of the nitro group and aromatic system of 8-hydroxyoquinoline.
      The computation of equilibrium geometry using MP2/cc-pVXZ (X = T, Q) shows a
      large overestimation of the phi value, while DFT with the cc-pVTZ basis set
      performs reasonably well. On the other hand, DFT computations with double-zeta
      basis sets yield a planar structure of NXN. The refined potential energy surface
      of the torsion vibration the of nitro group in the condensed phase derived from
      the THz-TDS data indicates the NXN molecule to be planar. This result stays in
      good agreement with the previous X-ray structure determination. The strength of
      the pi-system conjugation for the NO2 group and 8-hydroxyoquinoline is discussed
      using NBO analysis, being further supported by comparison of the refined
      semiexperimental gas-phase structure of NXN from GED with other nitrocompounds.

PMID- 29360362
TI  - Taccalonolide Microtubule Stabilizers Generated Using Semisynthesis Define the
      Effects of Mono Acyloxy Moieties at C-7 or C-15 and Disubstitutions at C-7 and C
      25.
AB  - The taccalonolides are a unique class of microtubule stabilizers isolated from
      Tacca spp. that have efficacy against drug-resistant tumors. Our previous studies
      have demonstrated that a C-15 acetoxy taccalonolide, AF, has superior in vivo
      antitumor efficacy compared to AJ, which bears a C-15 hydroxy group. With the
      goal of further improving the in vivo efficacy of this class of compounds, we
      semisynthesized and tested the biological activities of 28 new taccalonolides
      with monosubstitutions at C-7 or C-15 or disubstitutions at C-7 and C-25,
      covering a comprehensive range of substituents from formic acid to anthraquinone
      2-carbonyl chloride. The resulting taccalonolide analogues with diverse C-7/C
      15/C-25 modifications exhibited IC50 values from 2.4 nM to >20 MUM, allowing for
      extensive in vitro structure-activity evaluations. This semisynthetic strategy
      was unable to provide a taccalonolide with improved therapeutic window due to
      hydrolysis of substituents at C-7 or C-15 regardless of size or steric bulk.
      However, two of the most potent new taccalonolides, bearing isovalerate
      modifications at C-7 or C-15, demonstrated potent and highly persistent antitumor
      activity in a drug-resistant xenograft model when administered intratumorally.
      This study demonstrates that targeted delivery of the taccalonolides to the tumor
      could be an effective, long-lasting approach to treat drug-resistant tumors.

PMID- 29360363
TI  - Capillary Condensation of Binary and Ternary Mixtures of n-Pentane-Isopentane-CO2
      in Nanopores: An Experimental Study on the Effects of Composition and
      Equilibrium.
AB  - Confinement in nanopores can significantly impact the chemical and physical
      behavior of fluids. While some quantitative understanding is available for how
      pure fluids behave in nanopores, there is little such insight for mixtures. This
      study aims to shed light on how nanoporosity impacts the phase behavior and
      composition of confined mixtures through comparison of the effects of static and
      dynamic equilibrium on experimentally measured isotherms and chromatographic
      analysis of the experimental fluids. To this end, a novel gravimetric apparatus
      is introduced and validated. Unlike apparatuses that have been previously used to
      study the confinement-induced phase behavior of fluids, this apparatus employs a
      gravimetric technique capable of discerning phase transitions in a wide variety
      of nanoporous media under both static and dynamic conditions. The apparatus was
      successfully validated against data in the literature for pure carbon dioxide and
      n-pentane. Then, isotherms were generated for binary mixtures of carbon dioxide
      and n-pentane using static and flow-through methods. Finally, two ternary
      mixtures of carbon dioxide, n-pentane, and isopentane were measured using the
      static method. While the equilibrium time was found important for determination
      of confined phase transitions, flow rate in the dynamic method was not found to
      affect the confined phase behavior. For all measurements, the results indicate
      qualitative transferability of the bulk phase behavior to the confined fluid.

PMID- 29360364
TI  - Classical Trajectory Study of Collision Energy Transfer between Ne and C2H2 on a
      Full Dimensional Accurate Potential Energy Surface.
AB  - Collision energy transfer plays an important role in gas phase reaction kinetics
      and relaxation of excited molecules. However, empirical treatments are generally
      adopted for the collisional energy transfer in the master equation based
      approach. In this work, classical trajectory approach is employed to investigate
      the collision energy transfer dynamics in the C2H2-Ne system. The entire
      potential energy surface is described as the sum of the C2H2 potential and
      interaction potential between C2H2 and Ne. It is highlighted that both parts of
      the entire potential are highly accurate. In particular, the interaction
      potential is fit to ~41 300 configurations determined at the level of CCSD(T)
      F12a/cc-pCVTZ-F12 with the counterpoise correction. Collision energy transfer
      dynamics are then carried out on this benchmark potential and the widely used
      Lennard-Jones and Buckingham interaction potentials. Energy transfers and related
      probability densities at different collisional energies are reported and
      discussed.

PMID- 29360365
TI  - Hydrated Ion Clusters in Hydrophobic Liquid: Equilibrium Distribution, Kinetics,
      and Implications.
AB  - Hydrophilic ions in oil phase tend to be hydrated in the presence of trace water
      and form hydrated clusters. The present paper elucidates the equilibrium size
      distribution of hydrated ion clusters and the microscopic rates of adsorption and
      desorption of water with the help of molecular dynamics simulations. The size
      distribution is derived from reversible work of hydration, which is nearly
      constant over the hydration number except for small clusters. The intrinsic rate
      constants of adsorption and desorption are evaluated to be in several psec order
      after correcting the diffusion. The microscopic hydration properties of ions in
      the oil phase play key roles in chemical reactions involving both hydrophilic and
      hydrophobic reactants as well as in the transport and reactivity of the ions in
      oil phase and at the water-oil interface.

PMID- 29360366
TI  - Deconstructing Prominent Bands in the Terahertz Spectra of H7O3+ and H9O4+:
      Intermolecular Modes in Eigen Clusters.
AB  - We report experimental vibrational action spectra (210-2200 cm-1) and calculated
      IR spectra, using recent ab initio potential energy and dipole moment surfaces,
      of H7O3+ and H9O4+. We focus on prominent far-IR bands, which postharmonic
      analyses show, arise from two types of intermolecular motions, i.e., hydrogen
      bond stretching and terminal water wagging modes, that are similar in both
      clusters. The good agreement between experiment and theory further validates the
      accuracy of the potential and dipole moment surfaces, which was used in a recent
      theoretical study that concluded that infrared photodissociation spectra of the
      cold clusters correspond to the Eigen isomer. The comparison between theory and
      experiment adds further confirmation of the need of postharmonic analysis for
      these clusters.

PMID- 29360367
TI  - Binding of Divalent Cations to Insulin: Capillary Electrophoresis and Molecular
      Simulations.
AB  - In the present study, we characterize the binding of divalent cations to insulin
      in aqueous salt solutions by means of capillary electrophoresis and molecular
      dynamics simulations. The results show a strong pH dependence. At low pH, at
      which all the carboxylate groups are protonated and the protein has an overall
      positive charge, all the cations exhibit only weak and rather unspecific
      interactions with insulin. In contrast, at close to neutral pH, when all the
      carboxylate groups are deprotonated and negatively charged, the charge
      neutralizing effect of magnesium, calcium, and zinc, in particular, on the
      electrophoretic mobility of insulin is significant. This is also reflected in the
      results of molecular dynamics simulations showing accumulation of cations at the
      protein surface, which becomes smaller in magnitude upon effective inclusion of
      electronic polarization via charge rescaling.

PMID- 29360368
TI  - Jahn-Teller Effect on Framework Flexibility of Hybrid Organic-Inorganic
      Perovskites.
AB  - Here we study the Jahn-Teller (JT) effect on framework flexibility of two
      analogous hybrid organic-inorganic perovskites, [C(NH2)3][Zn(HCOO)3] (1-Zn) and
      [C(NH2)3][Cu(HCOO)3] (2-Cu). Single-crystal nanoindentation measurements show
      that the elastic moduli and hardnesses of 1-Zn are up to ~52.0% and ~25.0%
      greater than those of the JT active 2-Cu. Temperature-dependent X-ray diffraction
      measurements indicate that the thermal expansion along the b-axis is switched
      from negative to positive by replacing Zn2+ with Cu2+ on the B-site. These stark
      distinctions in framework flexibility are primarily attributed to the ~10.0%
      elongation of Cu-O bonds induced by the JT effect and associated alterations in
      octahedral tilting and hydrogen-bonding. Our results demonstrate the prominence
      of the JT effect in the emerging hybrid perovskites and highlight the
      possibilities of tuning materials' properties using orbital order.

PMID- 29360369
TI  - Optical Properties of Saturated and Unsaturated Carbonyl Defects in Polyethylene.
AB  - Polyethylene (PE), one of the simplest and most used aliphatic polymers, is
      generally provided with a number of additives, in particular antioxidants,
      because of its tendency to get oxidized. Carbonyl defects, a product of the
      oxidation of PE, are occurring in various forms, in particular saturated ones,
      known as ketones, where a C?O double bond substitutes a CH2 group, and various
      unsaturated ones, i.e., with further missing hydrogens. Many experimental
      investigations of the optical properties in the visible/UV range mainly attribute
      the photoluminescence of PE to one specific kind of unsaturated carbonyls,
      following analogies to the emission spectra of similar small molecules. However,
      the reason why saturated carbonyls should not be optically detected is not clear.
      We investigated the optical properties of PE with and without carbonyl defects
      using perturbative GW and the Bethe-Salpeter equation in order to take into
      account excitonic effects. We discuss the calculated excitonic states in
      comparison with experimental absorption/emission energies and the stability of
      both saturated and unsaturated carbonyl defects. We conclude that the unsaturated
      defects are indeed the best candidate for the luminescence of oxidized PE, and
      the reason is mainly due to oscillator strengths.

PMID- 29360370
TI  - Organocatalytic Asymmetric Synthesis of alpha-Oxetanyl and alpha-Azetidinyl
      Tertiary Alkyl Fluorides and Chlorides.
AB  - Asymmetric thiourea and squaramide catalysis provides access to synthetically
      versatile alpha-oxetanyl and alpha-azetidinyl alkyl halides exhibiting a
      tetrasubstituted chiral carbon center with high yields and enantioselectivities.
      The products are readily transformed with negligible erosion of enantiopurity and
      excellent diastereoselectivity to a diverse group of multifunctional compounds
      including fluorooxindoles with two contiguous chirality centers, fluorinated
      heterocyclic spiranes, and polyspiro compounds.

PMID- 29360371
TI  - Thermolysis-Induced Two- or Multicomponent Tandem Reactions Involving Isocyanides
      and Sulfenic-Acid-Generating Sulfoxides: Access to Diverse Sulfur-Containing
      Functional Scaffolds.
AB  - Direct reaction of isocyanides with some sulfenic-acid-generating sulfoxides led
      to the effective formation of the corresponding thiocarbamic acid S-esters in
      good to high yields. A multicomponent reaction involving isocyanide, sulfoxide,
      and a suitable nucleophile has also been developed, providing ready access to a
      diverse range of sulfur-containing compounds, including isothioureas,
      carbonimidothioic acid esters, and carboximidothioic acid esters.

PMID- 29360372
TI  - Kinetics of Polymer Desorption from Colloids Probed by Aggregation-Induced
      Emission Fluorophore.
AB  - Polymer adsorption and desorption are fundamental in many industrial and
      biomedical applications. Here, we introduce a new method to monitor the polymer
      desorption kinetics in situ based on the behavior of aggregation-induced
      emission. Poly(ethylene oxide) and colloidal silica (SiO2) were used as a model
      system. It was found that the aggregation-induced emission method could be
      successfully used to determine the polymer desorption kinetics, and the polymer
      desorption followed the first-order kinetics. It was also found that the polymer
      desorption rate constant decreased with the increasing molecular weight, which
      could be described by a power law function kd ~ M-0.28, close to that of the
      adsorption rate constant.

PMID- 29360373
TI  - 1,6-Addition of Tertiary Carbon Radicals Generated From Alcohols or Carboxylic
      Acids by Visible-Light Photoredox Catalysis.
AB  - The addition of tertiary carbon radicals generated by an Ir-catalyzed visible
      light photocatalyst to electron-deficient 1,3-dienes proceeds in good yields to
      append a delta-substituted beta,gamma-unsaturated carbonyl fragment to a tertiary
      alcohol or carboxylic acid precursor and construct a new quaternary carbon
      center.

PMID- 29360374
TI  - Vanadium Diboride (VB2) Synthesized at High Pressure: Elastic, Mechanical,
      Electronic, and Magnetic Properties and Thermal Stability.
AB  - Vanadium diboride (VB2) with an AlB2-type structure has been synthesized at 8 GPa
      and 1700 K in a D-DIA-type multianvil apparatus. The obtained bulk modulus is B0
      = 262(2) GPa with fixed B' = 4.0 for VB2 via high-pressure X-ray diffraction
      measurements. Meanwhile, VB2 has also been demonstrated to possess a high Vickers
      hardness of 27.2 +/- 1.5 GPa, a high thermal stability of 1410 K in air, among
      the highest for transition-metal borides, and an extremely low resistivity value
      (41 MUOmega cm) at room temperature. Results from first-principles calculations
      regarding the mechanical and electronic properties of VB2 are largely consistent
      with the experimental observations and further suggest that VB2 possesses
      simultaneously the properties of a hard and refractory ceramic and those of an
      excellent electric conductor.

PMID- 29360375
TI  - Stable Magnetic Skyrmion States at Room Temperature Confined to Corrals of
      Artificial Surface Pits Fabricated by a Focused Electron Beam.
AB  - Stable confinement of elemental magnetic nanostructures, such as a single
      magnetic domain, is fundamental in modern magnetic recording technology. It is
      well-known that various magnetic textures can be stabilized by geometrical
      confinement using artificial nanostructures. The magnetic skyrmion, with novel
      spin texture and promise for future memory devices because of its topological
      protection and dimension at the nanometer scale, is no exception. So far,
      skyrmion confinement techniques using large-scale boundaries with limited
      geometries such as isolated disks and stripes prepared by conventional
      microfabrication techniques have been used. Here, we demonstrate an alternative
      technique confining skyrmions to artificial nanostructures (corrals) built from
      surface pits fabricated by a focused electron beam. Using aberration-corrected
      differential phase contrast scanning transmission electron microscopy, we
      directly visualized stable skyrmion states confined at a room temperature to
      corrals made of artificial surface pits on a thin plate of Co8Zn8Mn4. We observed
      a stable single-skyrmion state confined to a triangular corral and a unique
      transition into a triple-skyrmions state depending on the perpendicular magnetic
      field. Furthermore, we made an array of stable single-skyrmion states by using
      concatenated triangular corrals. Artificial control of skyrmion states with the
      present technique should be a powerful way to realize future nonvolatile memory
      devices using skyrmions.

PMID- 29360376
TI  - Transition-Metal-Free Suzuki-Type Cross-Coupling Reaction of Benzyl Halides and
      Boronic Acids via 1,2-Metalate Shift.
AB  - Cross-coupling of organoboron compounds with electrophiles (Suzuki-Miyaura
      reaction) has greatly advanced C-C bond formation and has been well received in
      medicinal chemistry. During the past 50 years, transition metals have played a
      central role throughout the catalytic cycle of this important transformation. In
      this process, chemoselectivity among multiple carbon-halogen bonds is a common
      challenge. In particular, selective oxidative addition of transition metals to
      alkyl halides rather than aryl halides is difficult due to unfavorable transition
      states and bond strengths. We describe a new approach that uses a single organic
      sulfide catalyst to activate both C(sp3) halides and arylboronic acids via a
      zwitterionic boron "ate" intermediate. This "ate" species undergoes a 1,2
      metalate shift to afford Suzuki coupling products using benzyl chlorides and
      arylboronic acids. Various diaryl methane analogues can be prepared, including
      those with complex and biologically active motifs. The reactions proceed under
      transition-metal-free conditions, and C(sp2) halides, including aryl bromides and
      iodides, are unaffected. The orthogonal chemoselectivity is demonstrated in the
      streamlined synthesis of highly functionalized diaryl methane scaffolds using
      multi-halogenated substrates. Preliminary mechanistic experiments suggest both
      the sulfonium salt and the sulfur ylide are involved in the reaction, with the
      formation of sulfonium salt being the slowest step in the overall catalytic
      cycle.

PMID- 29360377
TI  - Silver(I)-Catalyzed C4-H Amination of 1-Naphthylamine Derivatives with
      Azodicarboxylates.
AB  - A simple and efficient protocol for silver(I)-catalyzed picolinamide directed C4
      H amination of 1-naphthylamine derivatives with readily available
      azodicarboxylates has been developed, demonstrating a new approach to 1,4
      naphthalenediamine derivatives in high yields. Note that this reaction system
      could proceed under external-oxidant- and additive-free conditions (only requires
      5 mol % of AgOAc as the catalyst in acetone).

PMID- 29360378
TI  - Triligustilides A and B: Two Pairs of Phthalide Trimers from Angelica sinensis
      with a Complex Polycyclic Skeleton and Their Activities.
AB  - Two pairs of enantiomeric phthalide trimers [(-)/(+) triligustilides A (1a/1b)
      and (-)/(+) triligustilides B (2a/2b)] with complex polycyclic skeletons
      simultaneously possessing bridged, fused, and spiro ring systems were isolated
      from Angelica sinensis, together with two pairs of new phthalide dimers. The
      biogenetic pathways of new phthalides were proposed, and their bioactivities were
      also evaluated. This is the first time optically pure polymeric phthalides have
      been obtained from racemates, and their absolute configurations are reported.

PMID- 29360379
TI  - Ionic Specificity in Rapid Coagulation of Silica Nanoparticles.
AB  - The Smoluchowski theory has been widely accepted as the basic theory to estimate
      the rapid coagulation rate of colloidal particles in electrolyte solutions.
      However, because the size and specificity of molecules and ions are not taken
      into account, the theory is applicable only if the particle size is large enough
      to neglect the effects caused by the structured layers composed of water
      molecules, ions, and hydrated ions adsorbed on the colloidal surface. In the
      present study, the rapid coagulation rates of silica nanoparticles in
      concentrated chloride and potassium solutions were measured by using a low-angle
      light-scattering apparatus, and the dependence of the experimental value of rapid
      coagulation rate, KER, on the particle diameter, Dp, and also on the Gibbs free
      energy of hydration of ions, DeltaGhyd, was investigated extensively. The
      following were found. (1) When the particle size was small enough, the value of
      KER reduced exponentially not only with the decreasing particle size but also
      with the increasing value of (-DeltaGhyd) of cations (counterions) in the case of
      chloride solutions and with that of anions (coions) in the case of potassium
      solutions. (2) Silica nanoparticles of Dp ? 70 nm in 1 M KNO3 and KSCN solutions
      did not coagulate at all, although they coagulated at Dp ? 100 nm as in the other
      potassium solutions. These unexpected phenomena were explained by the proposed
      mechanisms.

PMID- 29360380
TI  - Ultraslow Phase Transitions in an Anion-Anion Hydrogen-Bonded Ionic Liquid.
AB  - A Raman spectroscopy study of 1-ethyl-3-methylimidazolium hydrogen sulfate,
      [C2C1im][HSO4], as a function of temperature, has been performed to reveal the
      role played by anion-anion hydrogen bond on the phase transitions of this ionic
      liquid. Anion-anion hydrogen bonding implies high viscosity, good glass-forming
      ability, and also moderate fragility of [C2C1im][HSO4] in comparison with other
      ionic liquids. Heating [C2C1im][HSO4] from the glassy phase results in cold
      crystallization at ~245 K. A solid-solid transition (crystal I -> crystal II) is
      barely discernible in calorimetric measurements at typical heating rates, but it
      is clearly revealed by Raman spectroscopy and X-ray diffraction. Raman
      spectroscopy indicates that crystal I has extended ([HSO4]-)n chains of hydrogen
      bonded anions but crystal II has not. Raman spectra recorded at isothermal
      condition show the ultraslow dynamics of cold crystallization, solid-solid
      transition, and continuous melting of [C2C1im][HSO4]. A brief comparison is also
      provided between [C2C1im][HSO4] and [C4C1im][HSO4], as Raman spectroscopy shows
      that the latter does not form the crystalline phase with extended anion-anion
      chains.

PMID- 29360381
TI  - Combination Rules for Morse-Based van der Waals Force Fields.
AB  - In traditional force fields (FFs), van der Waals interactions have been usually
      described by the Lennard-Jones potentials. Conventional combination rules for the
      parameters of van der Waals (VDW) cross-termed interactions were developed for
      the Lennard-Jones based FFs. Here, we report that the Morse potentials were a
      better function to describe VDW interactions calculated by highly precise quantum
      mechanics methods. A new set of combination rules was developed for Morse-based
      FFs, in which VDW interactions were described by Morse potentials. The new set of
      combination rules has been verified by comparing the second virial coefficients
      of 11 noble gas mixtures. For all of the mixed binaries considered in this work,
      the combination rules work very well and are superior to all three other existing
      sets of combination rules reported in the literature. We further used the Morse
      based FF by using the combination rules to simulate the adsorption isotherms of
      CH4 at 298 K in four covalent-organic frameworks (COFs). The overall agreement is
      great, which supports the further applications of this new set of combination
      rules in more realistic simulation systems.

PMID- 29360382
TI  - Does 8-Nitroguanine Form 8-Oxoguanine? An Insight from Its Reaction with *OH
      Radical.
AB  - 8-Nitroguanine (8-nitroG) formed due to nitration of guanine base of DNA plays an
      important role in mutagenesis and carcinogenesis. In the present contribution,
      state-of-the-art quantum chemical calculations using M06-2X density functional
      and domain-based local pair natural orbital-coupled cluster theory with single,
      double, and perturbative triple excitations (DLPNO-CCSD(T)) methods have been
      carried out to investigate the mechanism of reaction of *OH radical with 8-nitroG
      leading to the formation of 8-oxoguanine (8-oxoG) (one of the most mutagenic and
      carcinogenic derivatives of guanine) in gas phase and aqueous media. Calculations
      of barrier energies and rate constants involved in the addition reactions of *OH
      radical at different sites of 8-nitroguanine show that C8 and C2 sites are the
      most and least reactive sites, respectively. Relative stability and Boltzmann
      populations of adducts show that the adduct formed at the C8 site occurs
      predominantly in equilibrium. Our calculations reveal that 8-nitroG is very
      reactive toward *OH radical and is converted readily into 8-oxoG when attacked by
      *OH radicals, in agreement with available experimental observations.

PMID- 29360383
TI  - Cu-Catalyzed Synthesis of Fluoroalkylated Isoxazoles from Commercially Available
      Amines and Alkynes.
AB  - A one-pot protocol for the construction of fluoroalkylated isoxazoles directly
      from commercially available amines and alkynes is described. The reaction is
      scalable, operationally simple, regioselective, mild, and tolerant of a broad
      range of functional groups. As such, it could be viewed as a "click synthesis" of
      fluoroalkylated isoxazoles. Preliminary mechanistic investigations reveal that
      the transformation involves an unprecedented Cu-catalyzed cascade sequence
      involving RfCHN2.

PMID- 29360384
TI  - Facile Integration between Si and Catalyst for High-Performance Photoanodes by a
      Multifunctional Bridging Layer.
AB  - Designing high-quality interfaces is crucial for high-performance
      photoelectrochemical (PEC) water-splitting devices. Here, we demonstrate a facile
      integration between polycrystalline n+p-Si and NiFe-layered double hydroxide
      (LDH) nanosheet array by a partially activated Ni (Ni/NiOx) bridging layer for
      the excellent PEC water oxidation. In this model system, the thermally deposited
      Ni interlayer protects Si against corrosion and makes good contact with Si, and
      NiOx has a high capacity of hole accumulation and strong bonding with the
      electrodeposited NiFe-LDH due to the similarity in material composition and
      structure, facilitating transfer of accumulated holes to the catalyst. In
      addition, the back illumination configuration makes NiFe-LDH sufficiently thick
      for more catalytically active sites without compromising Si light absorption.
      This earth-abundant multicomponent photoanode affords the PEC performance with an
      onset potential of ~0.78 V versus reversible hydrogen electrode (RHE), a
      photocurrent density of ~37 mA cm-2 at 1.23 V versus RHE, and retains good
      stability in 1.0 M KOH, the highest water oxidation activity so far reported for
      the crystalline Si-based photoanodes. This bridging layer strategy is efficient
      and simple to smooth charge transfer and make robust contact at the
      semiconductor/electrocatalyst interface in the solar water-splitting systems.

PMID- 29360385
TI  - Enantioselective, Protecting-Group-Free Total Synthesis of Boscartin F.
AB  - In this work, the protecting-group-free total synthesis and stereochemical
      assignment of (-)-boscartin F have been reported. The key steps, including
      Sharpless asymmetric epoxidation, I2-mediated iodoetherification, aldol reaction,
      and ring-closing metathesis, allowed for rapid and highly stereoselective access
      to boscartin F. In addition, single-crystal X-ray crystallographic analysis of
      the semicarbazone derivative 22 confirmed the stereochemistry of boscartin F.

PMID- 29360386
TI  - Lesion Size Does Not Predict Outcomes in Fresh Osteochondral Allograft
      Transplantation.
AB  - BACKGROUND: Cartilage repair algorithms use lesion size to choose surgical
      techniques when selecting a cartilage repair procedure. The association of fresh
      osteochondral allograft (OCA) size with graft survivorship and subjective patient
      outcomes is still unknown. PURPOSE: To determine if lesion size (absolute or
      relative) affects outcomes after OCA transplantation. STUDY DESIGN: Cohort study;
      Level of evidence, 3. METHODS: The study included 156 knees in 143 patients who
      underwent OCA transplantation from 1998 to 2014 for isolated femoral condyle
      lesions. The mean age was 29.6 +/- 11.4 years, and 62.9% were male. The majority
      of patients (62.2%) presented for cartilage repair because of osteochondritis
      dissecans. The mean graft area, used as a surrogate for absolute size of the
      lesion, was 6.4 cm2 (range, 2.3-11.5 cm2). The relative size of the lesion was
      calculated as the tibial width ratio (TWR; ratio of graft area to tibial width)
      and affected femoral condyle ratio (AFCR; ratio of graft area to affected femoral
      condyle width) using preoperative radiographs. All patients had a minimum follow
      up of 2 years. Further surgical procedures were documented, and graft failure was
      defined as revision OCA transplantation or conversion to arthroplasty.
      International Knee Documentation Committee (IKDC) pain, function, and total
      scores were obtained. Satisfaction with OCA transplantation was assessed.
      RESULTS: The mean follow-up among patients with grafts remaining in situ was 6.0
      years (range, 1.9-16.5 years). The OCA failure rate was 5.8%. Overall
      survivorship of the graft was 97.2% at 5 years and 93.5% at 10 years. No
      difference in postoperative outcomes between groups was found in absolute or
      relative size. Change in IKDC scores (from preoperative to latest follow-up) was
      greater for knees with large lesions compared to knees with small lesions, among
      all measurement methods. Overall satisfaction with the results of OCA
      transplantation was 89.8%. CONCLUSION: The size of the lesion, either absolute or
      relative, does not influence outcomes after OCA transplantation for isolated
      femoral condyle lesions of the knee.

PMID- 29360387
TI  - Superfruits: Phytochemicals, antioxidant efficacies, and health effects - A
      comprehensive review.
AB  - The term "superfruit" has gained increasing usage and attention recently with the
      marketing strategy to promote the extraordinary health benefits of some exotic
      fruits, which may not have worldwide popularity. This has led to many studies
      with the identification and quantification of various groups of phytochemicals.
      This contribution discusses phytochemical compositions, antioxidant efficacies,
      and potential health benefits of the main superfruits such as acai, acerola, camu
      camu, goji berry, jaboticaba, jambolao, maqui, noni, and pitanga. Novel product
      formulations, safety aspects, and future perspectives of these superfruits have
      also been covered. Research findings from the existing literature published
      within the last 10 years have been compiled and summarized. These superfruits
      having numerous phytochemicals (phenolic acids, flavonoids, proanthocyanidins,
      iridoids, coumarins, hydrolysable tannins, carotenoids, and anthocyanins)
      together with their corresponding antioxidant activities, have increasingly been
      utilized. Hence, these superfruits can be considered as a valuable source of
      functional foods due to the phytochemical compositions and their corresponding
      antioxidant activities. The phytochemicals from superfruits are bioaccessible and
      bioavailable in humans with promising health benefits. More well-designed human
      explorative studies are needed to validate the health benefits of these
      superfruits.

PMID- 29360388
TI  - Personality correlates of pro-environmental attitudes.
AB  - There is considerable scientific interest in the psychological correlates of pro
      environmental attitudes and concerns. While much research has focused on
      demographic and social-psychological characteristics of individuals with pro
      environmental attitudes, our study explores the relations between personality
      traits and pro-environmental behaviours. The study found that Honesty,
      Agreeableness, Openness, Proactive personality and Pro-environmental attitude
      predict environmental behaviour. The main implication of the study is the fact
      that responsible environmental behaviour could be enhanced through programmes
      focused on the increase of the environmental awareness and the development of a
      more pro-ecological view.

PMID- 29360389
TI  - The real and subjective indoor environmental quality in schools.
AB  - Investigation of IEQ and subjective evaluation of IEQ by pupils is the main
      objective of this research work. For the monitoring two classrooms in primary
      school and two classrooms in art school were chosen. Very high CO2 levels were
      determined in both investigated schools. In three of four classrooms the
      statistically significant differences (p < 0.01) were reported between TVOC
      levels in autumn and spring. The recommended value for TVOC levels was exceeded
      in the range from 52 % to 53 % in autumn and from 52 % to 70 % in spring.
      Significant (p < 0.05) seasonal changes were found also for PM concentrations in
      each classroom. Significance difference in perception of IEQ factors between
      genders were observed for IAQ. This study showed a good consistency between data
      obtained from the measurement and data from the questionnaire study and thus,
      pointed to the good ability of pupils to evaluate the IEQ in their classrooms.

PMID- 29360390
TI  - Rigor Is Needed When Making Comparative Analyses of Biologics in Severe Asthma.

PMID- 29360391
TI  - "Failure-to-Identify" Hunting Incidents: A Resilience Engineering Approach.
AB  - Objective The objective was to develop an understanding, using the Functional
      Resonance Analysis Method (FRAM), of the factors that could cause a deer hunter
      to misidentify their intended target. Background Hunting is a popular activity in
      many communities. However, hunters vary considerably based on training,
      experience, and expertise. Surprisingly, safety in hunting has not received much
      attention, especially failure-to-identify hunting incidents. These are incidents
      in which the hunter, after spotting and targeting their quarry, discharge their
      firearm only to discover they have been spotting and targeting another human, an
      inanimate object, or flora by mistake. The hunter must consider environment,
      target, time of day, weather, and many other factors-continuously evaluating
      whether the hunt should continue. To understand how these factors can relate to
      one another is fundamental to begin to understand how incidents happen. Method
      Workshops with highly experienced and active hunters led to the development of a
      FRAM model detailing the functions of a "Hunting FRAM." The model was evaluated
      for correctness based on confidential and anonymous near-miss event submissions
      by hunters. Results A FRAM model presenting the functions of a hunt was produced,
      evaluated, and accepted. Using the model, potential sources of incidents or other
      unintended outcomes were identified, which in turn helped to improve the model.
      Conclusion Utilizing principles of understanding and visualization tools of the
      FRAM, the findings create a foundation for safety improvements potentially
      through training or safety messages based on an increased understanding of the
      complexity of hunting.

PMID- 29360392
TI  - Accuracy of optoelectronic plethysmography in childhood exercise-induced asthma.
AB  - OBJECTIVE: To assess the variations of end-expiratory volume of chest wall
      (EEVcw) measured by optoelectronic plethysmography (OEP) as a diagnostic tool in
      exercise-induced asthma (EIA) among asthmatic preschool children. METHODS: Forty
      children diagnosed with asthma were included in the study. Spirometry was used as
      a gold standard test for comparison with OEP. A 10% decline in forced expiratory
      volume in 1 second was considered positive for EIA. OEP was performed with 8
      cameras at a frequency of 60 Hz and 89 markers were placed on the thoraco
      abdominal surface of participants. Following bronchoprovocation testing on a
      treadmill, series of OEP and spirometry were conducted between 5 and 30 minutes
      after exercise. To obtain the ideal cut-off point, a receiver operating
      characteristic (ROC) curve was constructed for the largest EEVcw. The highest
      Youden index was used as criteria to obtain the cut-off point with the best
      sensitivity and specificity. RESULTS: Of the 40 children studied, 16 had EIA.
      According to the ROC curve, the cut-off point of 0.185% for EEWcw provided mean
      sensitivity (95% confidence interval) of 93.75% (0.69-0.99), for a specificity of
      83.33% (0.63-0.95), when using the largest increase in the period of 5-30 minutes
      post-exercise. The low area of the ROC was 0.93 (0.85-1.00) for p < 0.001.
      CONCLUSION: OEP can be accurately used to replace spirometry in asthmatic
      children unable to adequately execute the required manoeuvres.

PMID- 29360394
TI  - Chemical methods and techniques to monitor early Maillard reaction in milk
      products; A review.
AB  - Maillard reaction is an extensively studied, yet unresolved chemical reaction
      that occurs as a result of application of the heat and during the storage of
      foods. The formation of advanced glycation end products (AGEs) has been the focus
      of several investigations recently. These molecules which are formed at the
      advanced stage of the Maillard reaction, are suspected to be involved in
      autoimmune diseases in humans. Therefore, understanding to which extent this
      reaction occurs in foods, is of vital significance. Because of their composition,
      milk products are ideal media for this reaction, especially when application of
      heat and prolonged storage are considered. Thus, in this work several chemical
      approaches to monitor this reaction in an early stage are reviewed. This is
      mostly done regarding available lysine blockage which takes place in the very
      beginning of the reaction. The most popular methods and their applications to
      various products are reviewed. The methods including their modifications are
      described in detail and their findings are discussed. The present paper provides
      an insight into the history of the most frequently-used methods and provides an
      overview on the indicators of the Maillard reaction in the early stage with its
      focus on milk products and especially milk powders.

PMID- 29360393
TI  - Disproportionate Right Ventricular Dysfunction and Poor Survival in Group 3
      Pulmonary Hypertension.

PMID- 29360395
TI  - A novel rodent model of pregnancy complications associated with genetically
      determined angiotensin-converting enzyme (ACE) activity.
AB  - Brown Norway (BN) and Lewis (LW) inbred rat strains harbor different angiotensin
      converting enzyme ( Ace) polymorphisms that result in higher ACE activity in BN
      than LW rats. Thus we hypothesized that pregnant BN rats would show pregnancy
      complications linked to angiotensin II (AII) activity. We performed longitudinal
      and cross-sectional studies in pregnant LW and BN rats. We found that BN rats
      have significantly higher ACE activity and AII levels at prepregnancy and
      throughout pregnancy compared with LW rats, except at midgestation. BN placentas
      and maternal kidneys had significantly higher expression of AII receptor 1
      (AGTR1) and lower expression of AGTR2 than the respective LW placentas and
      maternal kidneys. Renin-angiotensin system activation in BN rats correlated with
      hypertension and proteinuria at gestational days 17-21, which were resolved after
      delivery. In addition, BN rat pregnancies were characterized by significant fetal
      loss, restricted growth in surviving fetuses, decreased uteroplacental blood
      flows, and decreased trophoblast remodeling of uterine arteries compared with LW
      pregnancies. Short-term losartan treatment significantly increased uteroplacental
      blood flow and fetal weight and decreased maternal blood pressure (BP) and
      proteinuria in BN pregnancies. In contrast, losartan treatment significantly
      decreased uteroplacental blood flow and fetal weight but had no significant
      effect on maternal BP in LW pregnancies. We conclude that Ace polymorphisms play
      an important role in the reproductive phenotype of BN and LW rats and that BN
      rats are a novel model of pregnancy complications in association with genetically
      controlled, increased ACE activity.

PMID- 29360396
TI  - Impact of weight loss achieved through a multidisciplinary intervention on
      appetite in patients with severe obesity.
AB  - The impact of lifestyle-induced weight loss (WL) on appetite in patients with
      obesity remains controversial. This study aimed to assess the short- and long
      term impact of WL achieved by diet and exercise on appetite in patients with
      obesity. Thirty-five (22 females) adults with severe obesity (body mass index:
      42.5 +/- 5.0 kg/m2) underwent a 2-yr WL program focusing on diet and exercise.
      Body weight (BW), cardiovascular fitness (Vo2max), appetite feelings, and plasma
      concentrations of insulin, active ghrelin (AG), glucagon-like peptide 1 (GLP-1),
      peptide YY (PYY), and cholecystokinin (CCK), in the fasting and postprandial
      states, were measured at baseline (B), week 4 (W4), and 1 and 2 yr (and average
      values for all fasting and postprandial time points computed). BW was
      significantly reduced and Vo2max (ml.kg-1.min-1) increased at all time points
      compared with B (3.5, 8.1, and 8.4% WL and 7, 11, and 8% increase at W4 and 1 and
      2 yr, respectively). Basal hunger and average hunger and desire to eat were
      significantly increased at 1 and 2 yr. Basal fullness was significantly increased
      at W4, and average ratings were reduced at 1 yr. Average AG and PYY were
      significantly increased, and insulin was reduced, at all time points compared
      with B. Average GLP-1 was reduced at W4, and CCK was increased at 2 yr. After
      lifestyle-induced WL, patients with severe obesity will, therefore, have to deal
      with increased hunger in the long term. In conclusion, sustained WL at 2 yr
      achieved with diet and exercise is associated with increased hunger feelings and
      ghrelin concentration but also increased postprandial concentrations of satiety
      hormones.

PMID- 29360398
TI  - Effect of High Pressures in Combination with Temperature on the Inactivation of
      Spores of Nonproteolytic Clostridium botulinum Types B and F.
AB  - The impact of high pressure processing on the inactivation of spores of
      nonproteolytic Clostridium botulinum is important in extended shelf life chilled
      low-acid foods. The three most resistant C. botulinum strains (Ham-B, Kap 9-B,
      and 610-F) were selected for comparison of their thermal and pressure-assisted
      thermal resistance after screening 17 nonproteolytic C. botulinum strains (8 type
      B, 7 type E, and 2 type F). Spores of strains Ham-B, Kap 9-B, and 610-F were
      prepared using a biphasic media method, diluted in N-(2-acetamido)-2
      aminoethanesulfonic acid (ACES) buffer (0.05 M, pH 7.00) to 105 to 106 CFU/mL,
      placed into a modified sterile transfer pipette, heat sealed, and subjected to a
      combination of high pressures (600 to 750 MPa) and high temperatures (80 to 91
      degrees C) using laboratory and pilot-scale pressure test systems. Diluted spores
      from the same crops were placed in nuclear magnetic resonance tubes, which were
      heat sealed, and subjected to 80 to 91 degrees C in a Fluke 7321 high precision
      bath with Duratheram S oil as the heat transfer fluid. After incubation for 3
      months, survivors in both studies were determined by the five-tube most-probable
      number method using Trypticase-peptone-glucose-yeast extract broth. The highest
      (>5.0) log reductions in spore counts for Ham-B, Kap 9-B, and 610-F occurred at
      the highest temperature and pressure combination tested (91 degrees C and 750
      MPa). Thermal D-values of Ham-B, Kap 9-B, and 610-F decreased as the process
      temperature increased from 80 to 87 degrees C, decreasing to <1.0 min at 87
      degrees C for these strains. Pressure-assisted thermal D-values of Ham-B, Kap 9
      B, and 610-F decreased as the process temperature increased from 80 to 91 degrees
      C with any pressure combination and decreased to <1.0 min as the pressure
      increased from 600 to 750 MPa at 91 degrees C. Based on the pressure-assisted
      thermal D-values, pressure exerted a more protective effect on spores of Ham-B,
      Kap 9-B, and 610-F when processed at 83 to 91 degrees C combined with pressures
      of 600 to 700 MPa when compared with thermal treatment only. No protective effect
      was observed when the spores of Ham-B, Kap9-B, and 610-F were treated at lower
      temperatures (80 to 83 degrees C) in combination with 750 MPa. However, at higher
      temperatures (87 to 91 degrees C) in combination with 750 MPa, a protective
      effect was seen for Ham-B, Kap9-B, and 610-F spores based on the calculated
      pressure-assisted thermal D-values.

PMID- 29360397
TI  - Practice patterns for the radical treatment of nasopharyngeal cancer by head and
      neck oncologists in the United Kingdom.
AB  - OBJECTIVE: Advances in radiation delivery, imaging techniques, and chemotherapy
      have significantly improved treatment options for non-metastatic nasopharyngeal
      cancers (NPC). However, their impact on the practice in the United Kingdom (UK),
      where this tumour is rare, is unknown. This study examined the current attitudes
      of UK head and neck oncologists to the treatment of NPC. METHODS: UK head and
      neck oncologists representing 19/23 cancer networks were sent an invitation email
      with a personalised link to a web-based survey designed to identify the influence
      of tumour and nodal staging on current NPC management practices. RESULTS: 26/42
      (61%) of clinicians responded. Induction chemotherapy followed by concomitant
      chemoradiation was the treatment of choice for Stage III (69%) and IVa/b (96%),
      with cisplatin and 5-fluorouracil combination being the most commonly used
      induction chemotherapy regimen (88%). 16 centres (61%) used a geometric approach,
      adding variable margins of 0-10 mm to the gross tumour volume to define their
      therapeutic dose clinical target volume. 54% of respondents used 3 radiotherapy
      (RT) prescription doses to treat NPC. Retropharyngeal nodal region irradiation
      policy was inconsistent, with nearly one-quarter treating the entire group to a
      radical dose. CONCLUSION: Significant heterogeneity currently exists in the RT
      practice of NPC in the UK. A consensus regarding the optimal curative, function
      sparing treatment paradigm for NPC is necessary to ensure cancer survivors have
      satisfactory long-term health-related quality of life. Advances in knowledge:
      This is the first study to highlight the significant variation in RT practice of
      NPC in the UK.

PMID- 29360399
TI  - Prevalence, Antimicrobial Resistance, and Genetic Diversity of Listeria spp.
      Isolated from Raw Chicken Meat and Chicken-Related Products in Malaysia.
AB  - Listeria spp. are ubiquitous in nature and can be found in various environmental
      niches such as soil, sewage, river water, plants, and foods, but the most
      frequently isolated species are Listeria monocytogenes and Listeria innocua. In
      this study, the presence of Listeria spp. in raw chicken meat and chicken-related
      products sold in local markets in Klang Valley, Malaysia was investigated. A
      total of 44 Listeria strains (42 L. innocua and 2 L. welshimeri) were isolated
      from 106 samples. Antibiotic susceptibility tests of the L. innocua strains
      revealed a high prevalence of resistance to clindamycin (92.9%), ceftriaxone
      (76.2%), ampicillin (73.8%), tetracycline (69%), and penicillin G (66.7%).
      Overall, 31 L. innocua and 1 L. welshimeri strain were multidrug resistant, i.e.,
      nonsusceptible to at least one antimicrobial agent in three or more antibiotic
      classes. The majority of the L. innocua strains were placed into five AscI
      pulsogroups, and overall 26 distinct AscI pulsotypes were identified. The
      detection of multidrug-resistant Listeria strains from different food sources and
      locations warrants attention because these strains could serve as reservoirs for
      antimicrobial resistance genes and may facilitate the spread and emergence of
      other drug-resistant strains.

PMID- 29360400
TI  - Surfactant-Enhanced Organic Acid Inactivation of Tulane Virus, a Human Norovirus
      Surrogate.
AB  - Combination treatments of surfactants and phenolic or short-chain organic acids
      (SCOA) may act synergistically or additively as sanitizers to inactive foodborne
      viruses and prevent outbreaks. The purpose of this study was to investigate the
      effect of gallic acid (GA), tannic acid, p-coumaric acid, lactic acid (LA), or
      acetic acid (AA), in combination with sodium dodecyl sulfate (SDS), against
      Tulane virus (TV), a surrogate for human norovirus. An aqueous stock solution of
      phenolic acids or SCOA with or without SDS was prepared and diluted in a twofold
      dilution series to 2* the desired concentration with cell growth media (M119 plus
      10% fetal bovine serum). The solution was inoculated with an equal proportion of
      6 log PFU/mL TV with a treatment time of 5 min. The survival of TV was quantified
      using a plaque assay with LLC-MK2 cells. The minimum virucidal concentration was
      0.5:0.7% (v/v) for LA-SDS at pH 3.5 (4.5-PFU/mL reduction) and 0.5:0.7% (v/v) AA
      SDS at pH 4.0 (2.6-log PFU/mL reduction). GA and SDS demonstrated a minimum
      virucidal concentration of 12.5 mM GA-SDS at pH 7.0 (0.2:0.3% GA-SDS) with an 0.8
      log PFU/mL reduction and 50 mM GA-SDS (0.8:1.4% GA-SDS at pH 7.0) increased log
      reduction to 1.6 log PFU/mL. The combination treatments of AA or LA with SDS at
      pH 7.0 did not produce significant log reduction, nor did individual treatments
      of tannic acid, GA, p-coumaric acid, AA, LA, or SDS. This study demonstrates that
      a surfactant, such as SDS, aids in the phenolic acid and SCOA toxicities against
      viruses. However, inactivation of TV by combination treatments is contingent upon
      the pH of the sanitizing solution being lower than the pKa value of the organic
      acid being used. This information can be used to develop sanitizing washes to
      disinfect food contact surfaces, thereby aiding in the prevention of foodborne
      outbreaks.

PMID- 29360401
TI  - Backyard Farms Represent a Source of Wide Host Range Salmonella Phages That Lysed
      the Most Common Salmonella Serovars.
AB  - The genus Salmonella has more than 2,600 serovars, and this trait is important
      when considering interventions for Salmonella control. Bacteriophages that are
      used for biocontrol must have an exclusively lytic cycle and the ability to lyse
      several Salmonella serovars under a wide range of environmental conditions.
      Salmonella phages were isolated and characterized from 34 backyard production
      systems (BPSs) with a history of Salmonella infections. BPSs were visited once,
      and cloacal or fecal samples were processed for phage isolation. Four hosts,
      Salmonella serovars Enteritidis, Heidelberg, Infantis, and Typhimurium, were used
      for phage isolation. The host range of the phages was later characterized with a
      panel of 23 Salmonella serovars (serovar diversity set) and 31 isolates obtained
      from the same farms (native set). Genetic relatedness for 10 phages with a wide
      host range was characterized by restriction fragment length polymorphism, and
      phages clustered based on the host range. We purified 63 phages, and 36 phage
      isolates were obtained on Salmonella Enteritidis, 16 on Salmonella Heidelberg,
      and 11 on Salmonella Infantis. Phages were classified in three clusters: (i)
      phages with a wide host range (cluster I), (ii) phages that lysed the most
      susceptible Salmonella serovars (serogroup D) and other isolates (cluster II),
      and (iii) phages that lysed only isolates of serogroup D (cluster III). The most
      susceptible Salmonella serovars were Enteritidis, Javiana, and Dublin. Seven of
      34 farms yielded phages with a wide host range, and these phages had low levels
      of genetic relatedness. Our study showed an adaptation of the phages in the
      sampled BPSs to serogroup D Salmonella isolates and indicated that isolation of
      Salmonella phages with wide host range differs by farm. A better understanding of
      the factors driving the Salmonella phage host range could be useful when
      designing risk-based sampling strategies to obtain phages with a wide lytic host
      range for biocontrol purposes.

PMID- 29360402
TI  - Growth and Hemolysin Production Behavior of Vibrio parahaemolyticus in Different
      Food Matrices.
AB  - The growth and hemolytic activity profiles of two Vibrio parahaemolyticus strains
      (ATCC 17802 and ATCC 33847) in shrimp, oyster, freshwater fish, pork, chicken,
      and egg fried rice were investigated, and a prediction system for accurate
      microbial risk assessment was developed. The two V. parahaemolyticus strains
      displayed a similar growth and hemolysin production pattern in the foods at 37
      degrees C. Growth kinetic parameters showed that V. parahaemolyticus displayed
      higher maximum specific growth rate and shorter lag time values in shrimp >
      freshwater fish > egg fried rice> oyster > chicken > pork. Notably, there was a
      similar number of V. parahaemolyticus in all of these samples at the stationary
      phase. The hemolytic activity of V. parahaemolyticus in foods increased linearly
      with time ( R2 > 0.97). The rate constant ( K) of hemolytic activity was higher
      in shrimp, oyster, freshwater fish, and egg fried rice than in pork and chicken.
      Significantly higher hemolytic activity of V. parahaemolyticus was evident in egg
      fried rice > shrimp > freshwater fish > chicken > oyster > pork. The above
      mentioned results indicate that V. parahaemolyticus could grow well regardless of
      the food type and that contrary to current belief, it displayed a higher
      hemolytic activity in some nonseafood products (freshwater fish, egg fried rice,
      and chicken) than in one seafood (oyster). The prediction system consisting of
      the growth model and hemolysin production algorithm reported here will fill a gap
      in predictive microbiology and improve significantly the accuracy of microbial
      risk assessment of V. parahaemolyticus.

PMID- 29360403
TI  - Evaluation of Peroxyacetic Acid for Reducing Low Levels of Salmonella on
      Laboratory-Inoculated and Naturally Contaminated In-Shell Hazelnuts.
AB  - In-shell hazelnuts may be exposed to many sources of Salmonella during harvest
      and postharvest processing. Chemical sanitizers, such as peroxyacetic acid (PAA),
      are used by some postharvest processors in an attempt to reduce microbial loads;
      however, data are limited on its efficacy to reduce Salmonella on in-shell
      hazelnuts under conditions relevant to the industry. This study analyzed the
      efficacy of PAA to reduce small numbers of Salmonella on laboratory-inoculated
      (3.9 most probable number [MPN] per hazelnut) and naturally contaminated in-shell
      hazelnuts (8.2 MPN/33 g). Batches of hazelnuts (333 to 1,500 g) were agitated in
      water or PAA (80 or 200 ppm) for 1 min. Inoculated hazelnuts were analyzed for
      the presence of Salmonella on an individual nut basis. Naturally contaminated
      hazelnuts were analyzed for the presence of Salmonella in larger sample sizes (33
      g). Water and PAA (80 ppm) were effective at reducing Salmonella contamination on
      laboratory-inoculated hazelnuts (untreated, 85.5% positive; water, 38.7%; and
      PAA, 29.5%). Neither water nor PAA treatments (80 and 200 ppm) were effective in
      reducing Salmonella on naturally contaminated hazelnuts. The use of PAA in wash
      lines is unlikely to reduce Salmonella contamination on in-shell hazelnuts;
      however, PAA may reduce cross-contamination during postharvest washing
      activities.

PMID- 29360404
TI  - Cross-correlation between the controlled collision environment and real-world
      motor vehicle collisions: Evaluating the protection of the thoracic side airbag.
AB  - OBJECTIVE: Thoracic side airbags (tSABs) were integrated into the vehicle fleet
      to attenuate and distribute forces on the occupant's chest and abdomen, dissipate
      the impact energy, and move the occupant away from the intruding structure, all
      of which reduce the risk of injury. This research piece investigates and
      evaluates the safety performance of the airbag unit by cross-correlating data
      from a controlled collision environment with field data. METHOD: We focus
      exclusively on vehicle-vehicle lateral impacts from the NHTSA's Vehicle Crash
      Test Database and NASS-CDS database, which are replicated in the controlled
      environment by the (crabbed) barrier impact. Similar collisions with and without
      seat-embedded tSABs are matched to each other and the injury risks are compared.
      RESULTS: Results indicated that dummy-based thoracic injury metrics were
      significantly lower with tSAB exposure (P <.001). Yet, when the controlled
      collision environment data were cross-correlated with NASS-CDS collisions,
      deployment of the tSAB indicated no association with thoracic injury (tho. MAIS
      2+ unadjusted relative risk [RR] = 1.14; 90% confidence interval [CI], 0.80-1.62;
      tho. MAIS 3+ unadjusted RR = 1.12; 90% CI, 0.76-1.65). CONCLUSION: The data from
      the controlled collision environment indicated an unequivocal benefit provided by
      the thoracic side airbag for the crash dummy; however, the real-world collisions
      demonstrate that no benefit is provided to the occupant. This has resulted from a
      noncorrelation between the crash test/dummy-based design taking the abstracting
      process too far to represent the real-world collision scenario.

PMID- 29360405
TI  - Sepsis-associated Encephalopathy Is Septic.

PMID- 29360406
TI  - Effect of Hip-Focused Injury Prevention Training for Anterior Cruciate Ligament
      Injury Reduction in Female Basketball Players: A 12-Year Prospective Intervention
      Study.
AB  - BACKGROUND: Programs to prevent anterior cruciate ligament (ACL) injuries in
      female basketball players are scarce. Also, ACL injury prevention training that
      focuses on hip joint function has not been reported. PURPOSE: To determine the
      effectiveness of a hip-focused ACL injury prevention program in female basketball
      players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A prospective
      intervention study was conducted for 12 years. Incidence rates of ACL injuries
      were collected in the first 4 years (observation period) from college female
      basketball players. After the observation period, a hip-focused ACL injury
      prevention program was implemented for 8 years (intervention period). A total of
      309 players (mean +/- SD age, 19.6 +/- 1.2 years; height, 163.7 +/- 5.6 cm;
      weight, 59.1 +/- 5.1 kg; body mass index, 22.0 +/- 1.4) were tracked in the
      observation period and compared with 448 players (age, 19.6 +/- 1.1 years;
      height, 162.6 +/- 5.8 cm; weight, 58.0 +/- 5.7 kg; body mass index, 21.9 +/- 1.5)
      who participated in the intervention period. Athlete-exposures (AEs), ACL numbers
      and mechanisms of injury (MOIs), relative risk (RR), absolute risk reduction
      (ARR), numbers needed to treat (NNT), and compliance were analyzed. RESULTS:
      There were 16 ACL injuries (13 noncontact MOIs) in the 4-year observation period,
      whereas 9 ACL injuries (8 noncontact MOIs) were recorded in the 8-year
      intervention period. The overall ACL injury incidence was 0.25/1000 AEs in the 4
      year observation period compared with 0.10/1000 AEs in the 8-year intervention
      period, respectively. Compared with the 4-year observation period, significant RR
      reduction was observed (0.38; 95% CI, 0.17-0.87; P = .017) with ARR and NNT of
      0.032 (95% CI, 0.027-0.037) and 31.6 (95% CI, 27.1-37.7), respectively, in the 8
      year intervention period. The noncontact ACL injury incidence was 0.21 per 1000
      AEs during the 4-year observation period compared with 0.08/1000 AEs in the 8
      year intervention period, which also showed significant RR reduction (0.37; 95%
      CI, 0.15-0.92; P = .026), with ARR and NNT of 0.024 (95% CI, 0.020-0.029) and
      41.3 (95% CI, 34.6-51.3), respectively. The mean compliance rate during the
      intervention periods (8 years) was 89%. CONCLUSION: A hip-focused injury
      prevention program demonstrated significant reduction in the incidence of ACL
      injury in female collegiate basketball players.

PMID- 29360407
TI  - Otolaryngology Service Usage in Children With Cleft Palate.
AB  - OBJECTIVES: To determine the usage of otolaryngology services by children with
      cleft palate at a pediatric tertiary care facility. DESIGN: Retrospective case
      series. SETTING: Specialty clinic at a pediatric tertiary care hospital.
      PATIENTS: Children born between January 1, 1999, and December 31, 2002, with the
      diagnosis of cleft palate or cleft lip and palate. A total of 41 female and 48
      male patients were included. MAIN OUTCOME MEASURES: Total number of
      otolaryngology clinic visits and total number of otolaryngologic surgeries
      (tympanostomy tube placements and other otologic or upper airway procedures).
      RESULTS: In the first 5 years of life, these children utilized an average of 8.2
      otolaryngology clinic visits (SD = 5.0; range: 1-22) and underwent 3.3
      tympanostomy tube surgeries (SD = 2.0; range: 0-10). Seventy-three had their
      first tube placed at the time of palate repair, and 4 at the time of lip repair.
      Fifty-one (57.3%) required other otologic or upper airway procedures, including
      tonsillectomy and/or adenoidectomy (27 children), removal of tympanostomy tubes
      (24 children), tympanomastoidectomy (3 children), and tympanoplasty (14
      children). Of the children who underwent other procedures, they underwent a mean
      of 1.67 (SD = 0.84; range: 1-4) surgeries. CONCLUSIONS: Children with cleft
      palate are at increased risk for eustachian tube dysfunction, frequently utilize
      otolaryngology care, and typically receive multiple sets of tympanostomy tubes.
      This study found that children with cleft palate receive on average of
      approximately 3 sets of tympanostomy tubes, and the majority required another
      otologic or upper airway surgery.

PMID- 29360408
TI  - Centralization of Cleft Lip and Palate Services in the United Kingdom: The Views
      of Adult "Returners".
AB  - BACKGROUND: Since the implementation of centralized services in the United
      Kingdom for those affected by cleft lip and/or palate (CL/P), several studies
      have investigated the impact of service rationalization on the delivery of care.
      While large-scale quantitative studies have demonstrated improvements in a range
      of patient outcomes, and smaller studies have reported on the benefits and
      challenges of centralization from the views of health professionals, little
      research has attempted to capture the patient perspective. Furthermore, few
      studies have investigated the views of adult "returners" who have undergone
      treatment both pre- and postcentralization. METHODS: Qualitative data relevant to
      the subject of this article were extracted from 2 previous larger studies carried
      out between January 2013 and March 2014. A total of 16 adults born with CL/P
      contributed data to the current study. These data were subjected to inductive
      thematic analysis. RESULTS: The findings suggest that centralization of CL/P
      services has considerably enhanced the patient experience. Specifically, the
      overall standard and coordination of care has improved, service delivery has
      become more patient centered, and access to professional psychological support
      and peer support has greatly improved patients' capacity to cope with the
      associated emotional challenges. CONCLUSIONS: The data collected provide
      additional insight into the impact of centralization from the perspective of a
      largely unexplored patient population. In combination with other literature,
      these findings are also relevant to future efforts to centralize other specialist
      services around the world.

PMID- 29360409
TI  - Differences in the Tensor Veli Palatini Between Adults With and Without Cleft
      Palate Using High-Resolution 3-Dimensional Magnetic Resonance Imaging.
AB  - OBJECTIVE: To investigate the dimensions of the tensor veli palatini (TVP) muscle
      in adults with and without cleft palate. DESIGN: Prospective study. PARTICIPANTS:
      There were a total of 14 adult participants, 8 noncleft and 6 with cleft palate.
      METHODS: Analysis and comparison of the TVP muscle and surrounding structures was
      completed using 3D MRI data and Amira 5.5 Visualization Modeling software. TVP
      muscle volume, hamular process distance, mucosal thickness, TVP muscle length,
      and TVP muscle diameter were used for comparison between participant groups based
      upon previous research methods. RESULTS: Mann-Whitney U tests revealed a
      significantly smaller ( U < .001, P = .002) TVP muscle volume in the cleft palate
      group (median = 536.22 mm3) compared to individuals in the non-cleft palate group
      (median = 895.19 mm3). The TVP muscle was also significantly shorter ( U = 1.00,
      P = .003) in the cleft palate group (median = 18.04 mm) versus the non-cleft
      palate (median = 21.18 mm). No significant differences were noted for the other
      measured parameters. CONCLUSION: Significant differences in the TVP muscle volume
      and length among the noncleft participants found in this study may insights into
      the reported increased incidence of otitis media with effusion (OME) seen in the
      cleft population. Results from this study contribute to our understanding of the
      underlying anatomic differences among individuals with cleft palate.

PMID- 29360410
TI  - An Intraoral Appliance to Retract the Protrusive Premaxilla in Bilateral Cleft
      Lip Patients Presenting Late for Primary Lip Repair.
AB  - The protruding and deviated premaxilla in bilateral complete cleft lip and palate
      (BCL/P) patients causes a perplexing problem in achieving a tension-free primary
      lip closure. An innovative noninvasive active intraoral Fixed Pre-Surgical Cleft
      Orthopedic (FPSCO) appliance is presented that has enabled to successfully
      reposition the premaxillary segment to a more favorable position prior to the
      surgical repair in 4 BCL/P patients, who reported late for treatment with a mean
      age of 18 +/- 3 months. All the patients had at least 1 deciduous tooth erupted
      in 3 cleft segments, 1 premaxilla (PM), and 2 lateral maxillary (LM) segments.
      This innovative approach is a noninvasive method of getting the cleft segments
      closer prior to chelioplasty, where conventional presurgical nasoalveolar molding
      (PNAM) is not possible, which needs to be done early in life as it requires
      circulating maternal estrogen levels to achieve results preferably possible in
      patients younger than 3 to 6 months. Bonding to erupted teeth with glass ionomer
      cement was implemented to secure the appliance. Nickel-titanium (Ni-Ti) closed
      coil springs were used that delivered continuous forces of 150 g/5 oz per side to
      retract the premaxillary segment. The mean active period of treatment time was
      3.5 +/- 1.6 months and the retention period was 1.2 +/- 0.6 months, following
      which cheiloplasty was performed.

PMID- 29360411
TI  - Preparation and evaluation of carfentanil nasal spray employing cyclodextrin
      inclusion technology.
AB  - Carfentanil (CFTN), a derivative of fentanyl, is highly effective as an
      analgesic, but its relatively poor solubility in water has limited its nasal
      application. The objective of this study was to develop the new CFTN-CD inclusion
      technology to increase the solubility of CFTN. The inclusion compound CFTN-DM
      beta-CD was prepared by the ultrasonic method and characterized using X-ray
      powder diffraction and morphological shapes analysis (the scanning electron
      microscopy). The in vitro dissolution profiles of CFTN-DM-beta-CD were assessed
      in hydrochloric acid and phosphate buffer. Nasal ciliotoxicity studies were
      carried out using isolated toad palate. Rats were treated with CFTN-DM-beta-CD
      (250 ug/kg) by intravenous, intramuscular injection, oral, or nasal drops. The
      results showed that CFTN was successfully enveloped by DM-beta-CD. The in vitro
      cumulative dissolution of CFTN-DM-beta-CD was obviously enhanced compared to free
      CFTN in two buffers. Nasal ciliotoxicity studies have shown that the CFTN-DM-beta
      CD does not exhibit higher nasal ciliotoxicity than that of free CFTN.
      Pharmacokinetic studies demonstrated that CFTN-DM-beta-CD by nasal administration
      was absorbed more rapidly and has higher Cmax and bioavailability than that of
      either intramuscular injection or oral administration. In conclusion, the CFTN-DM
      beta-CD nasal spray was shown to be a relatively safe dosage form for the rapid
      and effective intranasal delivery of CFTN.

PMID- 29360412
TI  - Impact of various solid carriers and spray drying on pre/post compression
      properties of solid SNEDDS loaded with glimepiride: in vitro-ex vivo evaluation
      and cytotoxicity assessment.
AB  - Development of self-nanoemulsifying drug delivery systems (SNEDDS) of glimepiride
      is reported with the aim to achieve its oral delivery. Lauroglycol FCC, Tween-80,
      and ethanol were used as oil, surfactant, and co-surfactant, respectively as
      independent variables. The optimized composition of SNEDDS formulation (F1) was
      10% v/v Lauroglycol FCC, 45% v/v Tween 80, 45% v/v ethanol, and 0.005% w/v
      glimepiride. Further, the optimized liquid SNEDDS were solidified through spray
      drying using various hydrophilic and hydrophobic carriers. Among the various
      carriers, Aerosil 200 was found to provide desirable flow, compression,
      dissolution, and diffusion. Both, liquid and solid-SNEDDS have shown release of
      more than 90% within 10 min. Results of permeation studies performed on Caco-2
      cell showed that optimized SNEDDS exhibited 1.54 times higher drug permeation
      amount and 0.57 times lower drug excretion amount than that of market tablets at
      4 hours (p < .01). Further, the cytotoxicity study performed on Caco-2 cell
      revealed that the cell viability was lower in SNEDDS (92.22% +/- 4.18%) compared
      with the market tablets (95.54% +/- 3.22%; p > .05, i.e. 0.74). The formulation
      was found stable with temperature variation and freeze thaw cycles in terms of
      droplet size, zeta potential, drug precipitation and phase separation.
      Crystalline glimepiride was observed in amorphous state in solid SNEDDS when
      characterized through DSC, PXRD, and FT-IR studies. The study revealed successful
      formulation of SNEDDS for glimepiride.

PMID- 29360413
TI  - Low Incidence of Osteonecrosis in Childhood Acute Lymphoblastic Leukemia Treated
      With ALL-97 and ALL-02 Study of Japan Association of Childhood Leukemia Study
      Group.
AB  - Purpose Osteonecrosis (ON) is a serious complication of the treatment of
      childhood acute lymphoblastic leukemia (ALL); however, data relating to ON in
      Asian pediatric patients with ALL are scarce. Therefore, we performed a
      retrospective analysis of cohorts of Japanese patients with ALL to clarify the
      incidence, clinical characteristics, and risk factors of ON. Patients and Methods
      The incidence and characteristics of ON were determined in patients with ALL (n =
      1,662) enrolled in two studies from the Japan Association of Childhood Leukemia
      Study (JACLS) group (n = 635 and n = 1,027 patients treated with the ALL-97 and
      ALL-02 protocols, respectively). Results In total, 24 of 1,662 patients suffered
      from ON, of which 12 of 635 and 12 of 1,027 patients were treated with the ALL-97
      and the ALL-02 protocol, respectively. Of the 24 patients, 23 were older than 10
      years. In multivariate analysis, age (>= 10 years) was the sole significant risk
      factor for ON ( P < .001). Separate evaluation of patients >= 10 years of age
      indicated a 5-year cumulative incidence of ON of 7.2% (95% CI, 4.0% to 12.6%) and
      5.9% (95% CI, 3.3% to 10.4%) in the ALL-97 and the ALL-02 protocol, respectively,
      which was lower than reported previously, despite an administration of
      dexamethasone (DEX) similar to that in comparable studies; however, concomitant
      administration of DEX and l-asparaginase was reduced in the JACLS protocols.
      Conclusion We identified a low frequency of ON in the JACLS ALL-97 and ALL-02
      studies. Although the sole risk factor for ON was age (>= 10 years), even among
      high-risk patients, ON incidence was significantly lower than that reported in
      previous studies. These results suggest that, not only the total amount of DEX,
      but also how DEX and l-asparaginase are administered, which affects the clearance
      of DEX, may be associated with ON incidence in patients with ALL.

PMID- 29360414
TI  - Early Chemotherapy Intensification With Escalated BEACOPP in Patients With
      Advanced-Stage Hodgkin Lymphoma With a Positive Interim Positron Emission
      Tomography/Computed Tomography Scan After Two ABVD Cycles: Long-Term Results of
      the GITIL/FIL HD 0607 Trial.
AB  - Purpose To investigate the progression-free survival (PFS) of patients with
      advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was
      based on a positive positron emission tomography scan performed after two
      doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2).
      Patients and Methods Patients with advanced-stage (IIB to IVB) HL were
      consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally
      reviewed according to the Deauville five-point scale. Patients with a positive
      PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide,
      doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone
      (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab.
      Patients with a negative PET2 continued ABVD, and those with a large nodal mass
      at diagnosis (>= 5 cm) in complete remission with a negative PET at the end of
      chemotherapy were randomly assigned to radiotherapy or no further treatment. The
      primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had
      a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%.
      The 3-year PFS of those with a positive and negative PET2 was 60% and 87%,
      respectively ( P < .001). The 3-year PFS of patients with a positive PET2
      assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In
      296 patients with both interim and post-ABVD-negative PET who had a large nodal
      mass at diagnosis, radiotherapy was randomly added after chemotherapy without a
      significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year
      overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and
      positive, respectively). Conclusion The PET-driven switch from ABVD to escalated
      BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

PMID- 29360416
TI  - A Group Lifestyle Intervention Program Is Associated with Reduced Emergency
      Department Presentations for People with Metabolic Syndrome: A Retrospective Case
      Control Study.
AB  - BACKGROUND: One quarter of the world's adults have metabolic syndrome. Lifestyle
      modification is the first line of intervention as improvements in diet and
      exercise can have positive effects on the individual components of metabolic
      syndrome. The primary aim of this research was to evaluate the effect of an 8
      week lifestyle intervention program for people with metabolic syndrome on
      emergency department presentations, hospital admissions, and metabolic
      parameters. METHODS: A retrospective case-control study of adults (n = 58, mean
      age 60 +/- 7 years) with metabolic syndrome referred to a group lifestyle self
      management intervention program between 2013 and 2015. The intervention program
      consisted of 8 weekly sessions of group exercise and education delivered in a
      community healthcare setting. The intervention group (n = 29) was compared with a
      group of people who declined to attend the program (n = 29). Data were collected
      from the time a participant was referred to the program, and all participants
      were followed for a minimum of 100 days. RESULTS: Participants who attended the
      lifestyle intervention program had significantly fewer emergency department
      presentations [risk ratio (RR) 0.31, 95% confidence interval (CI) 0.11 to 0.83]
      and potentially avoidable emergency department presentations (RR 0.06, 95% CI
      0.004 to 0.097) over the follow-up period (mean 495 +/- 224 days per
      participant). There were no differences between the groups in hospital admissions
      and there were insufficient data to determine changes in metabolic parameters.
      Lifestyle group participants increased their exercise capacity [6-min walk test
      mean difference (MD) 41 m, 95% CI 20 to 62, P < 0.001] and had a mild decrease in
      weight (MD -0.8 kg, 95% CI -1.5 to -0.2, P = 0.018) and waist circumference (MD 
      1.3 cm, 95% CI -2.1 to -0.6, P = 0.002) after 8 weeks. CONCLUSIONS:
      Implementation of a group lifestyle intervention program to improve activity and
      self-management skills may assist in decreasing emergency department
      presentations.

PMID- 29360417
TI  - Advance Care Planning Documentation in Electronic Health Records: Current
      Challenges and Recommendations for Change.
AB  - OBJECTIVE: To develop a set of clinically relevant recommendations to improve the
      state of advance care planning (ACP) documentation in the electronic health
      record (EHR). BACKGROUND: Advance care planning (ACP) is a key process that
      supports goal-concordant care. For preferences to be honored, clinicians must be
      able to reliably record, find, and use ACP documentation. However, there are no
      standards to guide ACP documentation in the electronic health record (EHR).
      METHODS: We interviewed 21 key informants to understand the strengths and
      weaknesses of EHR documentation systems for ACP and identify best practices. We
      analyzed these interviews using a qualitative content analysis approach and
      subsequently developed a preliminary set of recommendations. These
      recommendations were vetted and refined in a second round of input from a
      national panel of content experts. RESULTS: Informants identified six themes
      regarding current inadequacies in documentation and accessibility of ACP
      information and opportunities for improvement. DISCUSSION: We offer a set of
      concise, clinically relevant recommendations, informed by expert opinion, to
      improve the state of ACP documentation in the EHR.

PMID- 29360415
TI  - Relationship of Circulating miRNAs with Insulin Sensitivity and Associated
      Metabolic Risk Factors in Humans.
AB  - BACKGROUND: Insulin resistance disrupts metabolic processes and leads to various
      chronic disease states such as diabetes and metabolic syndrome (MetS). However,
      the mechanism linking insulin resistance with cardiometabolic disease
      pathophysiology is still unclear. One possibility may be through circulating
      microRNAs (c-miRs), which can alter gene expression in target tissues. Our goal
      was to assess the relationship of c-miRs with insulin sensitivity, as measured by
      the gold standard, hyperinsulinemic-euglycemic clamp technique. METHODS: Eighty
      one nondiabetic, sedentary, and weight-stable patients across a wide range of
      insulin sensitivities were studied. Measurements were taken for blood pressure,
      anthropometric data, fasting glucose and lipids, and insulin sensitivity measured
      by clamp. After an initial screening array to identify candidate miRs in plasma,
      all samples were assessed for relationships between these c-miRs and insulin
      sensitivity, as well as associated metabolic factors. RESULTS: miR-16 and miR-107
      were positively associated with insulin sensitivity (R2 = 0.09, P = 0.0074 and R2
      = 0.08, P = 0.0417, respectively) and remained so after adjustment with body mass
      index (BMI). After adjusting for BMI, miR-33, -150, and -222 were additionally
      found to be related to insulin sensitivity. Regarding metabolic risk factors, miR
      16 was associated with waist circumference (r = -0.25), triglycerides (r = 
      0.28), and high-density lipoprotein (r = 0.22), while miR-33 was inversely
      associated with systolic blood pressure (r = -0.29). No significant relationships
      were found between any candidate c-miRs and BMI, diastolic blood pressure, or
      fasting glucose. CONCLUSIONS: Our results show that relative levels of
      circulating miR-16, -107, -33, -150, and -222 are associated with insulin
      sensitivity and metabolic risk factors, and suggest that multiple miRs may act in
      concert to produce insulin resistance and the clustering of associated traits
      that comprise the MetS. Therefore, miRs may have potential as novel therapeutic
      targets or agents in cardiometabolic disease.

PMID- 29360418
TI  - A Virtual Environment-Based Training System for a Blind Wheelchair User Through
      Use of Three-Dimensional Audio Supported by Electroencephalography.
AB  - People with disabilities encounter many difficulties, especially when a diagnosis
      of more than one dysfunction is made, as is the case for visually impaired
      wheelchair users. In fact, this scenario generates a degree of incapacity in
      terms of the performance of basic activities on the part of the wheelchair user.
      The treatment of disabled patients is performed in an individualized manner
      according to their particular clinical aspects. People with visual and motor
      disabilities are restricted in independent navigation. In this navigation
      scenario, there is a requirement for interaction that justifies the use of
      virtual reality (VR). In addition, locomotion needs to be under natural control
      to be successfully incorporated. Based on such a condition,
      electroencephalography (EEG) has shown great advances in the area of health by
      employing spontaneous brain signals. This research demonstrates, through an
      experiment, the use of a wheelchair adapted to have the support of VR and EEG for
      training of locomotion and individualized interaction of wheelchair users with
      visual impairment. The objective was to provide efficient interactions, thus
      allowing the social inclusion of patients who are considered otherwise
      incapacitated. This project was based on the following criteria: natural control,
      feedback, stimuli, and safety. A multilayer computer rehabilitation system was
      developed that incorporated natural interaction supported by EEG, which activated
      the movements in the virtual environment and real wheelchair through adequately
      performed experiments. This research consisted of elaborating a suitable approach
      for blind wheelchair user patients. The results demonstrated that the use of VR
      with EEG signals has the potential for improving the quality of life and
      independence of blind wheelchair users.

PMID- 29360419
TI  - Multiple Organ Dysfunction: The Defining Syndrome of Sepsis.
AB  - BACKGROUND: Sepsis as a process has been recognized since the time of the Ancient
      Greeks. The concept has evolved recently to reflect a disease process of a
      severe, systemic response to infection. Acute, life-threatening but potentially
      reversible organ dysfunction is its hallmark, and unresolving organ dysfunction
      is the dominant cause of death in critical illness. Its evolution, persistence,
      and resolution reflect a complex interplay of factors originating in the initial
      inciting insult, the innate immune and metabolic response of the host, and the
      beneficial and harmful consequences of intensive care unit (ICU) supportive care.
      DISCUSSION: We describe the common clinical manifestations of the six prototypic
      organ system dysfunction syndromes of severe sepsis and review the associated
      epidemiology and suspected pathophysiology.

PMID- 29360420
TI  - The informal use of antiretroviral medications for HIV prevention by men who have
      sex with men in South Florida: initiation, use practices, medications and
      motivations.
AB  - Limited data suggest that some gay and other men who have sex with men are using
      antiretroviral medications informally, without a prescription, for HIV
      prevention. This qualitative study examined this phenomenon among gay and other
      men who have sex with men in South Florida. Participants initiated informal
      antiretroviral medication use as a means of protecting each other and because of
      the confidence in knowledge of antiretroviral medications shared by their friends
      and sex partners. The most commonly used medications included Truvada and
      Stribild. Motivations for use included condom avoidance, risk reduction, and fear
      of recent HIV exposure. Participants described positive and negative sentiments
      related to informal use, including concerns about informal antiretroviral
      medications offering sufficient protection against HIV, and limited knowledge
      about pre-exposure prophylaxis (PrEP). Because the antiretroviral medications
      used for PrEP have the potential to prevent HIV infection, future research must
      consider the informal antiretroviral medication use and related concerns,
      including adherence, diversion and viral resistance.

PMID- 29360421
TI  - Prevalence and Correlates of Prescription Drug Misuse Among a Racially Diverse
      Sample of Young Sexual Minority Men.
AB  - PURPOSE: Sexual minority men (SMM) are at greater risk than heterosexual men for
      misusing prescription psychotropic medications. However, community prevalence
      estimates of prescription drug misuse among young SMM are lacking. The current
      study described lifetime and past-6-month stimulant, painkiller, and
      depressant/tranquilizer misuse in a large, racially diverse sample of 967 SMM
      aged 16-29 in Chicago, Illinois, and investigated demographic and other substance
      use associations. METHODS: Data came from the baseline visit of the RADAR
      longitudinal cohort study. Associations were examined using bivariate and
      multivariable logistic regression. RESULTS: A quarter of the sample reported ever
      misusing any prescription drug, and 14.2% reported recent misuse. Lifetime class
      specific misuse was 16.9% for stimulants, 11.0% for painkillers, and 11.4% for
      depressants/tranquilizers; recent misuse was 8.0%, 5.7%, and 6.2%, respectively.
      In multivariable analysis, Non-Hispanic black participants had lower odds of
      lifetime stimulant and depressant/tranquilizer misuse and recent stimulant misuse
      than non-Hispanic white participants, and bisexual participants had greater odds
      of lifetime and recent painkiller and depressant/tranquilizer misuse than gay
      participants. Generally, using other substances was associated with greater odds
      of prescription drug misuse. Having ever been prescribed a psychotropic
      medication was associated with higher odds of lifetime painkiller misuse after
      controlling for covariates. CONCLUSION: These results provide critical
      information on a growing public health problem among young SMM. Future research
      should explore why differential rates of misuse exist across subgroups. New
      interventions emphasizing the risk of prescription drugs, discouraging drug
      sharing, and bolstering refusal and coping skills should be developed and
      evaluated.

PMID- 29360422
TI  - Management of Acute Respiratory Failure in the Patient with Sepsis or Septic
      Shock.
AB  - Sepsis and septic shock are each commonly accompanied by acute respiratory
      failure and the need for invasive as well as non-invasive ventilation throughout
      a patient's intensive care unit course. We explore the underpinnings of acute
      respiratory failure of pulmonary as well as non-pulmonary origin in the context
      of invasive and non-invasive management approaches. Both pharmacologic and non
      pharmacologic adjuncts to ventilatory and oxygenation support are highlighted as
      well. Finally, rescue modalities are positioned within the intensivist's
      armamentarium for global care of support of the critically ill or injured patient
      with sepsis or septic shock.

PMID- 29360423
TI  - Efficacy for lung metastasis induced by the allogeneic bEnd3 vaccine in mice.
AB  - BACKGROUND: The mouse brain microvascular endothelial cell line bEnd.3 was used
      to develop a vaccine and its anti-tumor effect on lung metastases was observed in
      immunized mice. METHODS: Mouse bEnd.3 cells cultured in-vitro and then fixed with
      glutaraldehyde was used to immunize mice; mice were challenged with the
      metastatic cancer cell line U14, and changes in metastatic cancer tissues were
      observed through hematoxylin and eosin staining. Carboxyfluorescein succinimidyl
      amino ester (CSFE) and propidium iodide (PI) were used to detect cytotoxic
      activity of spleen T lymphocytes; the ratio of CD3+ and CD8+ T-cell sub-sets was
      determined by flow cytometry. Enzyme-linked immunosorbent assay (ELISA),
      immunocytochemistry and immunoblot were used to examine the specific response of
      the antisera of immunized mice. RESULTS: The number of metastatic nodules in
      bEnd.3 and human umbilical vein endothelial cell (HUVEC) vaccine groups was less
      than NIH3T3 vaccine group and phosphate buffered saline (PBS) control group. The
      bEnd.3-induced and HUVEC-induced cytotoxic T-lymphocytes (CTLs) showed
      significant lytic activity against bEnd.3 and HUVEC target cells, while the
      antisera of mice in bEnd.3 and HUVEC vaccine groups showed specific immune
      responses to membrane proteins and inhibited target cell proliferation in-vitro.
      Immunoblot results showed specific bands at 180KD and 220KD in bEnd.3 and at 130
      kD and 220 kD in HUVEC lysates. CONCLUSIONS: Allogeneic bEnd.3 vaccine induced an
      active and specific immune response to tumor vascular endothelial cells that
      resulted in production of antibodies against the proliferation antigens VEGF-R
      II, integrin, Endog etc. Immunization with this vaccine inhibited lung metastasis
      of cervical cancer U14 cells and prolonged the survival of these mice.

PMID- 29360424
TI  - Making a Good Impression at Work: National Differences in Employee Impression
      Management Behaviors in Japan, Korea, and the United States.
AB  - Impression management has important implications for success at work. This study
      explores differences in impression management in the East and West by examining
      the use of self-promotion, ingratiation, and exemplification directed towards
      three targets: supervisors, peers, and subordinates among 945 company employees
      from Japan, Korea, and the United States. Our results show that Korean employees
      used all three strategies most frequently, followed by United States, and then
      Japanese employees. Japanese and Korean employees used impression management
      strategies differentially across the three targets, and U.S. employees used
      impression management equally across targets. This elucidates how cultural trends
      in hierarchical relationships impact social behavior within the workplace. A
      follow-up mediation analysis found that relational or labor mobility fully
      mediated country differences in impression management, suggesting that culture is
      also reflected in larger social ecological trends in employee's ability and
      likelihood to change jobs, which also account for impression management strategy
      usage. Theoretical and practical implications for international business are
      discussed. This research may be useful in aligning strategies foreign employees
      might employ for using impression management when in Japan, Korea, and the United
      States.

PMID- 29360425
TI  - The use of home brew in Pacific Islands countries and territories.
AB  - This review examines what is known about the production and use of home brew in
      the Pacific Islands countries and territories. Data collection involved
      interviews of 78 men and women from the Marshall Islands, Papua New Guinea, Toga,
      and Tuvalu. The interviews were conducted in 2013 by local interviewers. The
      questions fell into four key areas: people's history of home-brew consumption,
      the reasons for home-brew use, the effects of home brew, and people's perceptions
      about home brew. An open ethnographic approach revealed that males are the main
      consumers of home brew, that home brew is consumed in private venues by those
      with low socioeconomic status, and that there are positive and negative outcomes
      associated with the use of home brew. Finally, policy implications of the
      findings are included in this article.

PMID- 29360426
TI  - Rhinofibroscopic and Rhinomanometric Evaluation of Patients with Maxillary
      Contraction Treated with Rapid Maxillary Expansion. A Prospective Pilot Study.
AB  - OBJECTIVE: The aim of this study was to evaluate through nasal fiber optic
      endoscopy and rhinomanometry the patency of upper nasal airways in patients
      treated with rapid palatal expansion Study design: 30 patients (12 males and 18
      females) aged 7-11 years with transverse maxillary constriction underwent
      rhinomanometric and fiberoptic examination before (T0) and after rapid palatal
      expansion (T1).The amount of nasopharynx obstruction was quantified with
      reference to the full choanal surface. Nasal resistance was recorded separately
      for right and left sides, and combined for both sides. The differences in
      nasopharynx obstruction and in nasal resistance between T0 and T1 were
      statistically evaluated. RESULTS: The amount of nasopharynx obstruction
      significantly decreased after palatal expansion (p<0.001). Total nasal
      inspiration and expiration resistance significantly decreased at T1 (p<0.001).
      The reduction ranged between 0. 23 and 0. 66 Pa/cm3/s for inspiration and between
      0. 20 and 0,.58 Pa/cm3/s for expiration. A statistically significant positive
      correlation existed between the T1-T0 differences in the amount of nasopharynx
      obstruction and the T1-T0 differences in expiration nasal airway resistance
      (Spearman's correlation coefficient rho = 0.38; p = 0.03). CONCLUSIONS: Rapid
      maxillary expansion has an influence on nasal resistance and improves the patency
      of upper airways in patients with minor or moderate breathing problems.

PMID- 29360427
TI  - Dental Decay and Oral Findings in Children and Adolescents Affected by Different
      Types of Cerebral Palsy: A Comparative Study.
AB  - OBJECTIVE: To compare dental caries and oral findings in patients affected by
      different types of Cerebral Palsy (CP). STUDY DESIGN: This cross-sectional study
      involved 120 children and adolescents with a diagnosis of CP. WHO diagnostic
      criteria were used to determine DMFT (caries diagnosis), the pocket depth and
      attachment level (periodontitis diagnosis). Additionally, the study evaluated
      dental erosion, traumatic dental injuries, treatment needs index (TNI), oral
      habits, malocclusions, gingival overgrowth, and dental fluorosis. RESULTS: The
      most frequent CP type was spastic (62.5%), followed by mixed (18.3%), ataxic
      (10%), and athetoid (9.1). Patients affected by mixed CP showed a higher
      prevalence in decayed, DMFT index and TNI compared with the other types of CP
      (p<0.05). The frequency of malocclusion in the clinical evaluation was 87.5% and
      in plaster models was 49.2%. CONCLUSIONS: Dental caries was an important issue in
      mixed and athetoid CP groups. Oral habits and malocclusions were the most
      significant oral health problems in individuals with CP.

PMID- 29360428
TI  - Hepatitis B Virus Infection and Hepatitis C Virus Treatment in a Large Cohort of
      Hepatitis C-Infected Patients in the United States.

PMID- 29360429
TI  - Retrospective evaluation of the clinical characteristics associated with
      Corynebacterium species bacteremia.
AB  - OBJECTIVES: Corynebacterium spp. are becoming recognized as pathogens that
      potentially cause various infections. We aimed to evaluate the clinical
      characteristics associated with Corynebacterium spp. bacteremia. PATIENTS AND
      METHODS: We retrospectively reviewed the medical records of all adult patients
      who had positive blood cultures for Corynebacterium spp. in a single university
      hospital between January 2014 and December 2016. Patients were divided into a
      bacteremia group and a contamination group based on microbiological test results
      and clinical characteristics. Patients' characteristics, antimicrobial
      susceptibility of isolated species, antimicrobials administered, and patient
      outcomes were evaluated. RESULTS: Corynebacterium spp. were isolated from blood
      samples of 63 patients; Corynebacterium striatum was the predominant isolate.
      Twenty-eight patients were determined to have bacteremia. Younger age (p=0.023),
      shorter time to positivity (p=0.006), longer hospital stay (p=0.009), and
      presence of an indwelling vascular catheter (p=0.002) were observed more often in
      the bacteremia group compared to the contamination group. The source of infection
      in most patients with bacteremia was an intravenous catheter. All tested strains
      were susceptible to vancomycin. Four of the 27 patients with bacteremia died,
      despite administration of appropriate antimicrobial therapy. CONCLUSIONS: We
      found that younger age, shorter time to positivity, and presence of an indwelling
      catheter were related to bacteremia caused by Corynebacterium spp. Appropriate
      antimicrobials should be administered once Corynebacterium spp. are isolated from
      the blood and bacteremia is suspected.

PMID- 29360431
TI  - Langmuir-monolayer methodologies for characterizing protein-lipid interactions.
AB  - The Langmuir-monolayer technique is a convenient method that allows for
      continuous control over several membrane-specific parameters, such as molecular
      packing, physical states, lateral pressure and lipid composition. Lipid
      monolayers are well suited for applications involving the Langmuir-monolayer
      technique: they are very well-defined, stable, homogeneous and two-dimensional,
      and they have planar geometry. In this review, some features of monolayer
      methodologies based on the Langmuir-monolayer technique are described, with a
      focus on the step-wise procedures that can be applied to characterize protein
      lipid interactions at the lipid monolayer/buffer interface in order to maximize
      the information concerning the mechanism of interaction between the protein and
      the lipid monolayer.

PMID- 29360430
TI  - Image analysis and machine learning for detecting malaria.
AB  - Malaria remains a major burden on global health, with roughly 200 million cases
      worldwide and more than 400,000 deaths per year. Besides biomedical research and
      political efforts, modern information technology is playing a key role in many
      attempts at fighting the disease. One of the barriers toward a successful
      mortality reduction has been inadequate malaria diagnosis in particular. To
      improve diagnosis, image analysis software and machine learning methods have been
      used to quantify parasitemia in microscopic blood slides. This article gives an
      overview of these techniques and discusses the current developments in image
      analysis and machine learning for microscopic malaria diagnosis. We organize the
      different approaches published in the literature according to the techniques used
      for imaging, image preprocessing, parasite detection and cell segmentation,
      feature computation, and automatic cell classification. Readers will find the
      different techniques listed in tables, with the relevant articles cited next to
      them, for both thin and thick blood smear images. We also discussed the latest
      developments in sections devoted to deep learning and smartphone technology for
      future malaria diagnosis.

PMID- 29360432
TI  - Multi-tasking Sulf1/Sulf2 enzymes do not only facilitate extracellular cell
      signalling but also participate in cell cycle related nuclear events.
AB  - This study demonstrates highly dynamic spatial and temporal pattern of
      SULF1/SULF2 expression in a number of neuronal cell types growing in normal
      culture medium that included their transient nuclear mobilisation. Their nuclear
      translocation became particularly apparent during cell proliferation as both
      SULF1/SULF2 demonstrated not only cell membrane associated expression, their
      known site of function but also transient nuclear mobilisation during nuclear
      cell division. Nuclear localisation was apparent not only by immunocytochemical
      staining but also confirmed by immunoblotting staining of isolated nuclear
      fractions of C6, U87 and N2A cells. Immunocytochemical analysis demonstrated
      rapid nuclear exit of both SULF1/SULF2 following cell division that was slightly
      delayed but not blocked in a fraction of the polyploid cells observed in C6
      cells. The overexpression of both Sulf1 and Sulf2 genes in C6 and U87 cells
      markedly promoted in vitro growth of these cells accompanied by nuclear
      mobilisation while inhibition of both these genes inhibited cell proliferation
      with little or no nuclear SULF1/SULF2 mobilisation. SULF1/SULF2 activity in these
      cells thus demonstrated a clear co-ordination of extracellular cell signalling
      with nuclear events related to cell proliferation.

PMID- 29360433
TI  - Quantitating transcription factor redundancy: The relative roles of the ELT-2 and
      ELT-7 GATA factors in the C. elegans endoderm.
AB  - The two GATA transcription factors ELT-2 and ELT-7 function in the
      differentiation of the C. elegans intestine. ELT-2 loss causes lethality. ELT-7
      loss causes no obvious phenotype but enhances the elt-2(-) intestinal phenotype.
      Thus, ELT-2 and ELT-7 appear partially redundant, with ELT-2 being more
      influential. To investigate the different regulatory roles of ELT-2 and ELT-7, we
      compared the transcriptional profiles of pure populations of wild-type, elt-2(-),
      elt-7(-), and elt-7(-); elt-2(-) double mutant L1-stage larvae. Consistent with
      the mutant phenotypes, loss of ELT-2 had a>25 fold greater influence on the
      number of significantly altered transcripts compared to the loss of ELT-7;
      nonetheless, the levels of numerous transcripts changed upon loss of ELT-7 in the
      elt-2(-) background. The quantitative responses of individual genes revealed a
      more complicated behaviour than simple redundancy/partial redundancy. In
      particular, genes expressed only in the intestine showed three distinguishable
      classes of response in the different mutant backgrounds. One class of genes
      responded as if ELT-2 is the major transcriptional activator and ELT-7 provides
      variable compensatory input. For a second class, transcript levels increased upon
      loss of ELT-2 but decreased upon further loss of ELT-7, suggesting that ELT-7
      actually overcompensates for the loss of ELT-2. For a third class, transcript
      levels also increased upon loss of ELT-2 but remained elevated upon further loss
      of ELT-7, suggesting overcompensation by some other intestinal transcription
      factor(s). In spite of its minor loss-of-function phenotype and its limited
      sequence similarity to ELT-2, ELT-7 expressed under control of the elt-2 promoter
      is able to rescue elt-2(-) lethality. Indeed, appropriately expressed ELT-7, like
      appropriately expressed ELT-2, is able to replace all other core GATA factors in
      the C. elegans endodermal pathway. Overall, this study focuses attention on the
      quantitative intricacies behind apparent redundancy or partial redundancy of two
      related transcription factors.

PMID- 29360435
TI  - Cerebellar oxidative stress and fine motor impairment in adolescent rats exposed
      to hyperthermia-induced seizures is prevented by maternal caffeine intake during
      gestation and lactation.
AB  - Febrile seizures (FS) is one of the most common convulsive disorders in infants
      and young children that only occurs during the first years of life in humans,
      when the cerebellum is still developing. Several works have shown that maternal
      caffeine consumption during gestation and lactation can exert protective effects
      on developing brain under pathological conditions. Here, we have used an animal
      model of FS to know whether maternal caffeine consumption during gestation and
      lactation exhibited protective effects on rat cerebellum. Pregnant rats were
      allowed to freely drink water or caffeine (1 g/l) during gestation and lactation.
      At PD13, neonates were submitted to hyperthermia-induced seizures (HIS) whereas
      pups not subject to hyperthermic stimulus were used as controls. 48 h, 5 and 20
      days after HIS, rats were killed and plasma membranes and cytosolic fractions
      were isolated from cerebella. The enzymatic activities of glutathione reductase,
      glutathione S-transferase, caspase-3, 5'-nucleotidase and the levels of
      thiobarbituric acid reacting substances, adenosine A1 and A2A receptors were
      studied in these preparations. Furthermore, rats were tested in balance beam test
      and footprint test 20 days after HIS (PD33) in order to investigate the effect on
      fine motor coordination and gait patterns. Results obtained suggest that maternal
      caffeine consumption during gestation and lactation exerts two kinds of
      beneficial effects on cerebellum from rats submitted to HIS: a) at short term,
      maternal caffeine abolishes hyperthermic seizures induced-oxidative stress and
      caspase-3 activation and b) in adolescent rats (PD33), maternal caffeine prevents
      fine motor coordination impairment and gait disturbances.

PMID- 29360434
TI  - Getting direction(s): The Eph/ephrin signaling system in cell positioning.
AB  - In vertebrates, the Eph/ephrin family of signaling molecules is a large group of
      membrane-bound proteins that signal through a myriad of mechanisms and effectors
      to play diverse roles in almost every tissue and organ system. Though Eph/ephrin
      signaling has functions in diverse biological processes, one core developmental
      function is in the regulation of cell position and tissue morphology by
      regulating cell migration and guidance, cell segregation, and boundary formation.
      Often, the role of Eph/ephrin signaling is to translate patterning information
      into physical movement of cells and changes in morphology that define tissue and
      organ systems. In this review, we focus on recent advances in the regulation of
      these processes, and our evolving understanding of the in vivo signaling
      mechanisms utilized in distinct developmental contexts.

PMID- 29360437
TI  - A Migratory Mishap: Giant Mediastinal Parathyroid Adenoma.

PMID- 29360436
TI  - Comprehensive circular RNA profiles in plasma reveals that circular RNAs can be
      used as novel biomarkers for systemic lupus erythematosus.
AB  - Circular RNAs (circRNAs), a novel class of widespread endogenous noncoding RNAs,
      have been involved in the development of various diseases, including
      atherosclerosis, Alzheimer's disease and several types of cancers, but there is
      little knowledge about their associations with systemic lupus erythematosus
      (SLE). This study is aimed to identify the expression profiles of circRNAs in 6
      paired SLE and normal participants plasma samples by using a circRNA microarray.
      The microarray analysis showed that 207 circRNAs were differentially expressed
      between these two groups, including 113 upregulated and 94 downregulated
      circRNAs. Then, we selected 8 circRNAs as candidate biomarkers from the
      microarray analysis and further verified them in another group of subjects
      consisting of 24 SLE patients and 24 normal controls using quantitative real-time
      polymerase chain reaction assays (qRT-PCR). Finally, we confirmed four circRNAs
      that were consistent with the microarray results. In addition, bioinformatics was
      employed to predict the interaction between validated circRNAs and potential
      miRNA targets. Taken together, we firstly illustrate the comprehensive expression
      profiles of circRNAs in SLE patients plasma and lay the foundations to develop
      circRNAs as novel non-invasive biomarkers for SLE disease in the future.

PMID- 29360438
TI  - Is there a role of H2S in mediating health span benefits of caloric restriction?
AB  - Caloric restriction (CR) is a dietary regimen that aims to reduce the intake of
      total calories while maintaining adequate supply of key nutrients so as to avoid
      malnutrition. CR is one of only a small number of interventions that show
      promising outcomes on health span and lifespan across different species. There is
      growing interest in the development of compounds that might replicate CR-related
      benefits without actually restricting food intake. Hydrogen sulfide (H2S) is
      produced inside the bodies of many animals, including humans, by evolutionarily
      conserved H2S synthesizing enzymes. Endogenous H2S is increasingly recognized as
      an important gaseous signalling molecule involved in diverse cellular and
      molecular processes. However, the specific role of H2S in diverse biological
      processes remains to be elucidated and not all its biological effects are
      beneficial. Nonetheless, recent evidence suggests that the biological functions
      of H2S intersect with the network of evolutionarily conserved nutrient sensing
      and stress response pathways that govern organismal responses to CR. Induction of
      H2S synthesizing enzymes appears to be a conserved and essential feature of the
      CR response in evolutionarily distant organisms, including nematodes and mice.
      Here we review the evidence for a role of H2S in CR and lifespan modulation. H2S
      releasing drugs, capable of controlled delivery of exogenous H2S, are currently
      in clinical development. These findings suggest such H2S releasing drugs as a
      promising novel avenue for the development of CR mimetic compounds.

PMID- 29360439
TI  - Dihydroartemisinin suppresses STAT3 signaling and Mcl-1 and Survivin expression
      to potentiate ABT-263-induced apoptosis in Non-small Cell Lung Cancer cells
      harboring EGFR or RAS mutation.
AB  - Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide. A
      significant fraction of NSCLC carries activating mutations in epidermal growth
      factor receptor (EGFR) or RAS oncogene. Dihydroartemisinin (DHA) is a
      semisynthetic derivative of the herbal antimalarial drug artemisinin that has
      been recently reported to exhibit anti-cancer activity. To develop new
      therapeutic strategies for NSCLC, we investigated the interactions between DHA
      and ABT-263 in NSCLC cells harboring EGFR or RAS mutation. Our data indicated
      that DHA synergized with ABT-263 to trigger Bax-dependent apoptosis in NSCLC
      cells in culture. DHA treatment antagonized ABT-263-induced Mcl-1 upregulation
      and sensitized NSCLC cells to ABT-263-triggered apoptosis. Additionally, DHA
      treatment caused downregulation of Survivin and upregulation of Bim, which also
      contribute to cotreatment-induced cytotoxicity. Moreover, DHA effectively
      suppressed STAT3 phosphorylation, and STAT3 inactivation resulted in the
      downregulation of Mcl-1 and Survivin, functioning to enhance ABT-263-induced
      cytotoxicity. Finally, cotreatment of DHA and ABT-263 significantly inhibited
      xenograft growth in nude mice. Together, DHA effectively inhibits STAT3 activity
      and modulates expression of Mcl-1, Survivin and Bim, thereby synergizing with ABT
      263 to trigger apoptosis in NSCLC cells harboring EGFR or RAS mutation. Our data
      provide a novel therapeutic strategy for EGFR or RAS mutant NSCLC treatment.

PMID- 29360441
TI  - Response From the Authors.

PMID- 29360440
TI  - A novel in-cell ELISA method for screening of compounds inhibiting TRKA
      phosphorylation, using KM12 cell line harboring TRKA rearrangement.
AB  - Tropomyosin-related kinase A (TRKA) fusion was originally detected in colorectal
      carcinoma that had resulted in expression of the oncogenic chimeric protein TPM3
      TRKA. Lately, many more rearrangements in TRK family of kinases generating
      oncogenic fusion proteins have been identified. These genetic rearrangements
      usually result in fusion of cytoplasmic kinase domain of TRK to another gene of
      interest resulting in constitutive kinase activity. Estimation of TRK inhibitor
      potency in a cellular context is required for drug discovery programs and is
      measured by receptor phosphorylation levels upon compound administration.
      However, since a large chunk of the TRK protein is lost in this rearrangement,
      it's difficult to set up sandwich ELISA for detection of receptor phosphorylation
      in any cell assay harboring these fusion proteins. In order to address this
      issue, we developed a novel and robust in-cell ELISA method which quantifies the
      phosphorylation of TRK kinase (Tyr 674/675) within the KM12 cells. This cell
      based method is more versatile & economical than conventional ELISA using
      engineered overexpressing cell line and/or western blot methods. Performance
      reliability & robustness for the validated assay were determined by %CV and Z
      factor in assays with reference molecule larotrectinib. This in-cell ELISA method
      can be used with any TRKA rearranged oncogenic fusion cell type and can be
      extended to other TRK isoforms as well. We have used this assay to screen novel
      molecules in KM12 cells and to study pharmacodynamic properties of compounds in
      TRKA signaling.

PMID- 29360444
TI  - Reply by Authors.

PMID- 29360442
TI  - Ultrastructural analysis of Apicomplexa-Like parasites in two conch species
      Laevistrombus canarium and canarium urceus from Johor Straits, Malaysia.
AB  - The tropical conch, Laevistrombus canarium (Linnaeus, 1758) and Canarium urceus
      (Linneaus, 1758) are ecologically and economically important shellfish species in
      Malaysia and neighboring region. Their populations, however are currently
      declining and this histopathological study investigates the aspect of parasitism
      and diseases that may affect their well-being. Conch samples were randomly
      collected from their natural habitat and histological sections (4-5 um) of
      various organs and tissues were examined under light microscope. This was
      followed by ultrastructure analysis on infected tissues using transmission
      electron microscope (TEM). Based on the histological analysis, large numbers of
      gamonts, sporocysts and trophozoites of Apicomplexa-like parasites were observed
      in the vacuolated cells and pyramidal crypt cells of the digestive tubules, and
      in the digestive ducts. Furthermore, coccidian and oocysts-like Pseudoklossia sp.
      stages were also observed in the cells of the kidney. Apart from that, spores
      with cyst-like structure were observed in the digestive gland and kidney.
      Although the parasites were present in most of the organs analyzed, there was no
      obvious symptom, inflammatory response or mortality incurred on both species,
      which implies the possibility of a non-virulent relationship like commensalisms
      or mutualism. However, more investigations, including molecular studies, are
      needed to confirm the parasite identification and dynamics, and to further
      evaluate the nature of relationship between Apicomplexa parasites and their host.

PMID- 29360445
TI  - Editorial Comment.

PMID- 29360446
TI  - A mouse model of a novel missense mutation (Gly83Arg) in a Chinese kindred
      manifesting vitreous amyloidosis only.
AB  - The purpose of this study is to establish a mouse model of transthyretin (TTR)
      Gly83Arg gene mutation by the technique of gene targeting for research on
      hereditary vitreous amyloidosis (HVA) and to confirm whether this point mutation
      is a genetic feature of HVA. A vector (pBR322-MK-TTR) was constructed to target
      ES cells. The successfully transfected ES cells were used for blastocyst
      injection, thus generating F0. F0 and Flp mice were mated to generate F1 (TTR+/-,
      Flp +/-) mice that lacked the neo gene but carried the Flp gene. F1 mice were
      mated with C57BL/6N wild type mice to generate F2 (TTR+/-) mice. F3 homozygous
      and heterozygous mice were generated by mating F2 mice with each other. PCR and
      sequencing were performed for F3 mice. Amyloid was detected using Congo red stain
      and polarized light. Immunohistochemistry was used to detect the expression of
      TTR in the tissues. Quantitative fluorescent PCR and Western blotting were used
      to detect the expression of TTR mRNA and TTR protein, respectively. Two F0
      generation, 2 F1-generation and 15 F3-generation mice were obtained. The gene
      sequencing of F3 mice showed TTR Gly83Arg mutation. When examined with Congo red
      and polarized light, the vitreous of TTR Gly83Arg mutant mice tested positive for
      amyloid. The hearts, livers, brains and kidneys of the experimental group and
      control group were all negative by Congo red staining. Immunohistochemical
      staining showed that the vitreous of TTR Gly83Arg mutant mice and the livers of
      the control mice were positive, but the kidneys, hearts and brains of both groups
      were negative. Quantitative fluorescent PCR showed that the mRNA expression of
      mutant mice was significantly lower than that of wild-type mice (F = 0.295, P =
      0.023). Western blotting showed that the expression of TTR protein was
      significantly lower in the model mice than in the wild-type mice (t = 3.224, P =
      0.018). TTR gene mutation is indeed a molecular characteristic of HVA and
      manifest in the eye disease only. A C57BL/6 mouse line carrying the TTR Gly83Arg
      gene mutation was successfully established. This strain of mice can be used for
      the study of HVA.

PMID- 29360447
TI  - MicroRNA regulation of MDM2-p53 loop in pterygium.
AB  - PURPOSE: The pathogenesis of pterygium has been linked to limbal stem cell
      damage, abnormal apoptosis and cellular proliferation. In this study, we
      investigated the epigenetic regulation through microRNA expression in the
      pathogenesis of pterygium. METHODS: Human full-length primary pterygia were
      microdissected into head and body regions. Specific microRNA and mRNA expression
      was assayed by TaqMan(r) real-time quantitative polymerase chain reaction (qPCR).
      Tissue localization of target microRNAs was performed by LNA-based in situ
      hybridization. MicroRNA-145 (miR-145) mimics were transfected to primary culture
      of human pterygial cells, followed by analyses of cell cycle changes, apoptosis,
      p53 and MDM2 expression using flow cytometry and qPCR. RESULTS: The expression of
      miR-145 was markedly higher in primary human pterygium than in limbus and
      conjunctiva. Both miR-143 and miR-145 were predominantly expressed in the basal
      pterygial epithelium. Oncogene MDM2 expression was abundant in pterygial
      epithelium and stroma, while the expression pattern was opposite to that of miR
      145. Ectopic expression of miR-145 in pterygial cells induced G1 arrest, down
      regulated MDM2 and elevated p53 expression. CONCLUSIONS: Our study showed that
      miR-145 suppressed MDM2 expression, which subsequently influenced the p53-related
      cell growth pattern in pterygial epithelium. The regulatory miR-145/MDM2-p53 loop
      can serve as a potential target for treatment of pterygium.

PMID- 29360448
TI  - Morphological analysis of corneal findings modifications after death: A
      preliminary OCT study on an animal model.
AB  - The aim of this work was to describe, for the first time, the morphological
      modifications, in a three-dimensional mode, of the central cornea at different
      intervals since death. The study design involved the analysis of 30 eyes (15
      heads) of female, adult sheep (>2 years) sacrificed at a local slaughterhouse.
      The eyes, after animal decapitation, were examined in situ, without enucleation.
      Ocular globes were stored at well-known temperature (within a range of 12-22 
      degrees C) and humidity (within a range of 50-60%). The instrumental analysis was
      executed using a portable spectral-domain OCT (SD-OCT) system (iVue SD-OCT,
      Optovue Inc, Fremont, CA) calibrated to the corneal mode. OCT imaging was
      performed at different time-points since death. Pachymetric map, morphological
      and ultrastructural analysis (epithelium, stroma, and endothelium), were
      performed for each time-point. After an initial thinning of tissues and an
      enhancement of epithelial reflectivity, stromal thickness increased from the 2nd
      up to the 6th hour. Subsequently, a new trend incorneal thinning was observed in
      association with the appearance ofone or more demarcation lines between the
      anterior andposterior stroma. After the 12th hour, a recurrence of corneal
      swelling was detected in association with thedelamination of stromal tissue.
      Since the 24th hour, the epithelium disappeared in 50% of cases and the anterior
      chamberdepth progressively decreased. At the 48th hour, various ocular structures
      showed the onset of putrefaction processes, such as theappearance of hyper
      reflective dots in anterior chamber, iridocorneal contact, and the massive
      vacuolization of theposterior stroma until the total delamination. The portable
      OCT system is a useful approach for in situ postmortem corneal examination, and
      it may be potentially applied for the selection of donor cornea in
      transplantology and for the determination of post-mortem intervals in forensic
      medicine.

PMID- 29360449
TI  - miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular
      carcinoma via targeting LDHA.
AB  - Cancer cells are addictively dependent on glycolysis even in an oxygen-rich
      condition. However, the mechanism underlying micro (mi)RNA regulation of aerobic
      glycolysis in cancer cells has not been fully understood. Here, we demonstrated
      that the expression of miR-142-3p was lower in hepatocellular carcinoma (HCC) as
      compared to adjacent non-tumor samples, which was confirmed in The Cancer Genome
      Atlas (TCGA) HCC cohorts and Gene Expression Omnibus (GEO) datasets. Function and
      pathway analysis showed that miR-142-3p was most relevent with metabolism. As
      predicted, the overexpression of miR-142-3p inhibited aerobic glycolysis and thus
      proliferation of HCC cells. Mechanistically, we identified lactate dehydrogenase
      A (LDHA), one of the important catalyticase for aerobic glycolysis, as the target
      of miR-142-3p. Exogenous expression of miR-142-3p reduced the protein levels of
      LDHA in both SK-Hep-1 and Huh7 cells. Dual luciferase report assays showed the
      expression of LDHA was directly modulated by miR-142-3p. miR-142-3p-induced
      deduction of aerobic glycolysis and proliferation were reversed by LDHA
      overexpression. Taken together, these results indicate that miR-142-3p could act
      as a tumor suppressor in HCC by targeting LDHA, suggesting new therapeutic
      targets for HCC treatment.

PMID- 29360450
TI  - Noninvasive, targeted gene therapy for acute spinal cord injury using LIFU
      mediated BDNF-loaded cationic nanobubble destruction.
AB  - Various gene delivery systems have been widely studied for the acute spinal cord
      injury (SCI) treatment. In the present study, a novel type of brain-derived
      neurotrophic factor (BDNF)-loaded cationic nanobubbles (CNBs) conjugated with MAP
      2 antibody (mAbMAP-2/BDNF/CNBs) was prepared to provide low-intensity focused
      ultrasound (LIFU)-targeted gene therapy. In vitro experiments, the ultrasound
      targeted tranfection to BDNF overexpressioin in neurons and efficiently
      inhibition neuronal apoptosis have been demonstrated, and the elaborately
      designed mAbMAP-2/BDNF/CNBs can specifically target to the neurons. Furthermore,
      in a acute SCI rat model, LIFU-mediated mAbMAP-2/BDNF/CNBs transfection
      significantly increased BDNF expression, attenuated histological injury,
      decreased neurons loss, inhibited neuronal apoptosis in injured spinal cords, and
      increased BBB scores in SCI rats. LIFU-mediated mAbMAP-2/BDNF/CNBs destruction
      significantly increase transfection efficiency of BDNF gene both in vitro and in
      vivo, and has a significant neuroprotective effect on the injured spinal cord.
      Therefore, the combination of LIFU irradiation and gene therapy through mAbMAP
      2/BDNF/CNBs can be considered as a novel non-invasive and targeted treatment for
      gene therapy of SCI.

PMID- 29360451
TI  - Phenomena of synchronized response in biosystems and the possible mechanism.
AB  - Phenomena of synchronized response is common among organs, tissues and cells in
      biosystems. We have analyzed and discussed three examples of synchronization in
      biosystems, including the direction-changing movement of paramecia, the prey
      behavior of flytraps, and the simultaneous discharge of electric eels. These
      phenomena and discussions support an electrical communication mechanism that in
      biosystems, the electrical signals are mainly soliton-like electromagnetic
      pulses, which are generated by the transient transmembrane ionic current through
      the ion channels and propagate along the dielectric membrane-based softmaterial
      waveguide network to complete synchronized responses. This transmission model
      implies that a uniform electrical communication mechanism might have been
      naturally developed in biosystem.

PMID- 29360452
TI  - Long noncoding RNA SNHG7 promotes the progression and growth of glioblastoma via
      inhibition of miR-5095.
AB  - The long non-coding RNA SNHG7 (small nucleolar RNA host gene 7) has been reported
      to be involved in various cancers as a potential oncogene. However, the functions
      and molecular mechanisms of SNHG7 in glioblastoma (GBM) are largely unknown. In
      the present study, we showed that the expression of SNHG7 was significantly
      upregulated in GBM tissues and cell lines compared with non-cancerous brain
      tissues. Furthermore, we found that SNHG7 knockdown remarkably suppressed the
      proliferation, migration and invasion of A172 and U87 cells while inducing their
      apoptosis. Subsequently, we showed that SNHG7 knockdown significantly inhibited
      tumor growth and metastasis in vivo by using xenograft experiments in nude mice.
      In terms of mechanism, we found that SNHG7 directly inhibited miR-5095, which
      targeted the 3' UTR of CTNNB1 mRNA and subsequently downregulated the Wnt/beta
      catenin signaling pathway in GBM. Using rescue experiments, we demonstrated that
      SNHG7 promoted the proliferation, migration and invasion of GBM cells through the
      inhibition of miR-5095 and concomitant activation of Wnt/beta-catenin signaling
      pathway. Taken together, the SNHG7/miR-5095 axis might be a potential target for
      the development of effective GBM therapy.

PMID- 29360453
TI  - The ABC transporter Rv1272c of Mycobacterium tuberculosis enhances the import of
      long-chain fatty acids in Escherichia coli.
AB  - Mycobacterium tuberculosis (Mtb), which causes tuberculosis, is capable of
      accumulating triacylglycerol (TAG) by utilizing fatty acids from host cells. ATP
      binding cassette (ABC) transporters are involved in transport processes in all
      organisms. Among the classical ABC transporters in Mtb none have been implicated
      in fatty acid import. Since the transport of fatty acids from the host cell is
      important for dormancy-associated TAG synthesis in the pathogen, mycobacterial
      ABC transporter(s) could potentially be involved in this process. Based on
      sequence identities with a bacterial ABC transporter that mediates fatty acid
      import for TAG synthesis, we identified Rv1272c, a hitherto uncharacterized ABC
      transporter in Mtb that also shows sequence identities with a plant ABC
      transporter involved in fatty acid transport. We expressed Rv1272c in E. coli and
      show that it enhances the import of radiolabeled fatty acids. We also show that
      Rv1272c causes a significant increase in the metabolic incorporation of
      radiolabeled long-chain fatty acids into cardiolipin, a tetra-acylated
      phospholipid, and phosphatidylglycerol in E. coli. This is the first report on
      the function of Rv1272c showing that it displays a long-chain fatty acid
      transport function.

PMID- 29360454
TI  - Regarding "Tube Decompression for Staged Treatment of a Calcifying Odontogenic
      Cyst-A Case Report".

PMID- 29360455
TI  - Comparative Evaluation of Clinical Outcomes Using Delta Plates and Conventional
      Miniplates for Internal Fixation of Mandibular Condylar Fractures in Adults.
AB  - PURPOSE: In recent years numerous osteosynthesis devices have become available
      for the management of condylar fractures. The aim of this study was to compare
      and evaluate the clinical outcomes of delta plates and conventional miniplates
      for internal fixation of mandibular condylar fractures in adults. MATERIALS AND
      METHODS: We performed a prospective study of 20 patients with subcondylar
      fractures requiring open reduction and internal fixation for their management.
      Patients were randomly divided into 2 groups using computer software: Group A
      patients (n = 10) were treated using delta plates whereas group B patients (n =
      10) were treated using conventional miniplates via an extraoral retromandibular
      transparotid approach. RESULTS: There was no statistically significant difference
      between delta plates and conventional miniplates for internal fixation of
      mandibular condylar fractures in adults. However, the time taken for adaptation
      of the delta plates was significantly lower than that required for the 2
      miniplates (P < .001), and the ease of adaptation was significantly better for
      the delta plates (P < .001). CONCLUSIONS: The study results indicated that the
      delta plate and miniplate are equally effective in terms of long-term clinical
      success in the management of mandibular subcondylar fractures in adults. The
      delta plate is superior in terms of handling characteristics, such as ease of
      adaptation and time required for adaptation, as only 1 plate and 4 screws are
      required as compared with 2 plates and 8 screws.

PMID- 29360456
TI  - Do Open Reduction and Internal Fixation With Articular Disc Anatomical Reduction
      and Rigid Anchorage Manifest a Promising Prospect in the Treatment of
      Intracapsular Fractures?
AB  - PURPOSE: In response to the increased attention to soft tissue reduction in the
      treatment of intracapsular condylar fractures (ICFs), a modified open reduction
      technique is proposed and its functional and radiographic outcomes were evaluated
      in this study. PATIENTS AND METHODS: This is a retrospective case series study of
      patients with all ICF types that were treated with open reduction and internal
      fixation (ORIF) with articular disc anatomic reduction and rigid anchorage.
      Inclusion and exclusion criteria were strictly applied. Preoperative and
      postoperative clinical examinations of malocclusion, maximum incisor opening
      (MIO), laterotrusion, and temporomandibular disorder symptoms were recorded and
      analyzed. Computed tomography (CT) and magnetic resonance imaging (MRI) were used
      to assess articular position and condylar morphology and position. RESULTS:
      Thirty-four patients with ICFs (47 sides) were treated with the modified ORIF
      technique. At 6 months of follow-up, no malocclusion was found and the MIO
      considerably expanded to 3.56 +/- 0.13 cm. Only 4 patients (12%) had
      temporomandibular joint discomfort with mouth opening. Interestingly, for
      unilateral type B ICFs, the laterotrusion distance to the ORIF sides was notably
      longer than to the non-ORIF sides. Postoperative CT and MRI showed that all
      fragments were properly reduced and the condyles were in the normal position.
      Postoperative anterior disc displacement occurred in 4 sides and condylar
      morphologic abnormalities (slight surface roughening and articular cartilage
      absorption) occurred in 3 sides (6.4%). CONCLUSIONS: This modified ORIF
      technique, which achieved good outcomes after treatment of all ICF types, shows
      promise for the treatment of ICFs.

PMID- 29360457
TI  - Intraosseous Schwannoma of the Jaws: An Updated Review of the Literature and
      Report of 2 New Cases Affecting the Mandible.
AB  - Schwannomas are benign nerve sheath neoplasms composed almost entirely of Schwann
      cells. These tumors most often arise in the soft tissues of the head and neck.
      However, they seldom occur within bone. This article presents a rare case of a
      recurrent intraosseous schwannoma of the anterior mandible and another case of a
      posterior intraosseous mandibular schwannoma accessed through a sagittal split
      ramus osteotomy. Furthermore, an updated review of the literature on intraosseous
      schwannomas affecting the mandible and maxilla is provided.

PMID- 29360458
TI  - Variation in Intraocular Pressure and the Risk of Developing Open-Angle Glaucoma:
      The Los Angeles Latino Eye Study.
AB  - PURPOSE: To determine whether measures of intraocular pressure (IOP) variation
      are independently associated with the risk of developing open-angle glaucoma
      (OAG). DESIGN: A population-based, longitudinal study. METHODS: A total of 3666
      Latinos free of OAG at the baseline of the Los Angeles Latino Eye Study were
      followed up 4 years later. Maximum IOP, standard deviation (SD) of IOP, range of
      IOP, and mean IOP were derived from 6 readings obtained at the 2 visits. OAG
      diagnosis at each visit was based on the consensus of experts who had access to
      all clinical examination data from that visit. Multivariate logistic regression
      was performed. RESULTS: Maximum, SD, and range of IOP were all associated with
      risk of developing OAG, and SD and range of IOP remained significantly associated
      even after adjustment for mean IOP. Maximum IOP provided the best fit to the data
      and other IOP measures were not associated with OAG risk in the model that had
      included maximum IOP. The effect of IOP variation varied by the level of IOP.
      Among participants with higher IOPs (>=15 mm Hg), only higher levels of maximum
      IOP were associated with a higher OAG risk (P < .05), while SD and range of IOP
      were not associated with OAG risk. Among participants with lower IOPs (<15 mm
      Hg), higher levels of maximum, SD, and range of IOP were all associated with a
      higher risk of developing OAG (P < .05). Mean IOP was associated with OAG risk
      only in participants with higher IOPs and not in those with lower IOPs. Results
      were similar when participants were stratified as <18 and >=18 mm Hg.
      CONCLUSIONS: IOP variation was an independent risk factor for OAG. Maximum IOP
      was the most consistent IOP measure for predicting OAG risk across the entire
      spectrum of IOPs, possibly by capturing the effect of IOP variation among persons
      with relative lower IOPs as well as mean IOP effects in those with higher IOPs.

PMID- 29360459
TI  - Assessment of Lamellar Macular Hole and Macular Pseudohole With a Combination of
      En Face and Radial B-scan Optical Coherence Tomography Imaging.
AB  - PURPOSE: To investigate lamellar macular hole (LMH) and macular pseudohole (MPH)
      using a combination of en face and radial B-scan OCT. DESIGN: Retrospective
      observational case series. METHODS: Setting: Institutional study. PATIENT
      POPULATION: En face and radial B-scan OCT images of 63 eyes of 60 patients
      diagnosed with LMH or MPH based on an international classification were reviewed.
      OBSERVATION PROCEDURES: Cases were classified using en face images based on the
      presence/absence of epiretinal membrane (ERM), retinal folds, parafoveal
      epicenter of contractile ERM (PEC-ERM), and retinal cleavage. We compared the en
      face imaging-based classification system with the international classification
      system using radial B-scan images. We quantitatively evaluated visual function
      and macular morphology. MAIN OUTCOME MEASURES: Characterization of multimodal OCT
      based subtypes of LMH and MPH. RESULTS: All cases showed ERM and were classified
      into 4 groups. In the first group, which lacked retinal folds and showed
      significantly lower visual acuity than the other groups, 81% of eyes had
      degenerative LMH. In the second group, which lacked PEC-ERM and retinal cleavage
      and showed significantly lower retinal fold depth, all eyes had MPH. The third
      group, in which 95% of eyes had symmetric tractional LMH, included eyes with
      retinal cleavage but without PEC-ERM, and this group showed higher circularity of
      the foveal aperture and cleavage area than the group with both these features, in
      which all eyes had asymmetric tractional LMH. CONCLUSIONS: Multimodal OCT enables
      classification of LMH and MPH based on pathologic conditions. Retinal traction in
      particular may be useful for determining treatment methods.

PMID- 29360460
TI  - The Relationship Between Nonsteroidal Anti-inflammatory Drug Use and Age-related
      Macular Degeneration.
AB  - PURPOSE: To describe the relationship between the incidence of age-related
      macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use.
      DESIGN: Prospective cohort study. METHODS: This study consisted of participants
      in the California Men's Health Study. Those who completed surveys in 2002-2003
      and 2006 were included. Men who self-reported use of aspirin, ibuprofen,
      naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3 days per week were
      considered NSAID users. Patients were categorized as non-users, former users, new
      users, or longer-term users based on survey responses. NSAID use was also
      categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age,
      race/ethnicity, smoking status, education, income, alcohol use, and Charlson
      comorbidity index score were included in the multivariate analysis as risk
      factors for AMD. RESULTS: A total of 51 371 men were included. Average follow-up
      time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and
      nonexudative AMD, respectively. Longer-term use of any NSAID was associated with
      lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI]
      0.50-0.96, P = .029). New users of any NSAIDs (HR = 0.79, 95% CI 0.68-0.93, P =
      .0039) and aspirin (HR = 0.82, 95% CI 0.70-0.97, P = .018) had a lower risk of
      nonexudative AMD, although this trend did not persist in longer-term users. The
      relationship between exudative or nonexudative AMD and the remaining categories
      of NSAID use were not significant. CONCLUSION: The overall impact of NSAIDs on
      AMD incidence is small; however, the lower risk of exudative AMD in longer-term
      NSAID users may point to a protective effect and deserves further study as a
      possible mechanism to modulate disease risk.

PMID- 29360461
TI  - Pancreatitis-Induced Depletion of Syntaxin 2 Promotes Autophagy and Increases
      Basolateral Exocytosis.
AB  - BACKGROUND & AIMS: Pancreatic acinar cells are polarized epithelial cells that
      store enzymes required for digestion as inactive zymogens, tightly packed at the
      cell apex. Stimulation of acinar cells causes the zymogen granules to fuse with
      the apical membrane, and the cells undergo exocytosis to release proteases into
      the intestinal lumen. Autophagy maintains homeostasis of pancreatic acini.
      Syntaxin 2 (STX2), an abundant soluble N-ethyl maleimide sensitive factor
      attachment protein receptor in pancreatic acini, has been reported to mediate
      apical exocytosis. Using human pancreatic tissues and STX2-knockout (KO) mice, we
      investigated the functions of STX2 in zymogen granule-mediated exocytosis and
      autophagy. METHODS: We obtained pancreatic tissues from 5 patients undergoing
      surgery for pancreatic cancer and prepared 80-MUm slices; tissues were exposed to
      supramaximal cholecystokinin octapeptide (CCK-8) or ethanol and a low
      concentration of CCK-8 and analyzed by immunoblot and immunofluorescence
      analyses. STX2-KO mice and syntaxin 2+/+ C57BL6 mice (controls) were given
      intraperitoneal injections of supramaximal caerulein (a CCK-8 analogue) or fed
      ethanol and then given a low dose of caerulein to induce acute pancreatitis, or
      saline (controls); pancreata were isolated and analyzed by histology and
      immunohistochemistry. Acini were isolated from mice, incubated with CCK-8, and
      analyzed by immunofluorescence microscopy or used in immunoprecipitation
      experiments. Exocytosis was quantified using live-cell exocytosis and Ca2+
      imaging analyses and based on formation of exocytotic soluble N-ethyl maleimide
      sensitive factor attachment protein receptor complexes. Dysregulations in
      autophagy were identified using markers, electron and immunofluorescence
      microscopy, and protease activation assays. RESULTS: Human pancreatic tissues and
      dispersed pancreatic acini from control mice exposed to CCK-8 or ethanol plus CCK
      8 were depleted of STX2. STX2-KO developed more severe pancreatitis after
      administration of supramaximal caerulein or a 6-week ethanol diet compared with
      control. Acini from STX2-KO mice had increased apical exocytosis after exposure
      to CCK-8, as well as increased basolateral exocytosis, which led to ectopic
      release of proteases. These increases in apical and basolateral exocytosis
      required increased formation of fusogenic soluble N-ethyl maleimide sensitive
      factor attachment protein receptor complexes, mediated by STX3 and STX4. STX2
      bound ATG16L1 and prevented it from binding clathrin. Deletion of STX2 from acini
      increased binding of AT16L1 to clathrin, increasing formation of pre
      autophagosomes and inducing autophagy. Induction of autophagy promoted the CCK-8
      induced increase in autolysosome formation and the activation of trypsinogen.
      CONCLUSIONS: In studies of human pancreatic tissues and pancreata from STX2-KO
      and control mice, we found STX2 to block STX3- and STX4-mediated fusion of
      zymogen granules with the plasma membrane and exocytosis and prevent binding of
      ATG16L1 to clathrin, which contributes to induction of autophagy. Exposure of
      pancreatic tissues to CCK-8 or ethanol depletes acinar cells of STX2, increasing
      basolateral exocytosis and promoting autophagy induction, leading to activation
      of trypsinogen.

PMID- 29360462
TI  - Association Between Portosystemic Shunts and Increased Complications and
      Mortality in Patients With Cirrhosis.
AB  - BACKGROUND & AIMS: Spontaneous portosystemic shunts (SPSS) have been associated
      with hepatic encephalopathy (HE). Little is known about their prevalence among
      patients with cirrhosis or clinical effects. We investigated the prevalence and
      characteristics of SPSS in patients with cirrhosis and their outcomes. METHODS:
      We performed a retrospective study of 1729 patients with cirrhosis who underwent
      abdominal computed tomography or magnetic resonance imaging analysis from 2010
      through 2015 at 14 centers in Canada and Europe. We collected data on demographic
      features, etiology of liver disease, comorbidities, complications, treatments,
      laboratory and clinical parameters, Model for End-Stage Liver Disease (MELD)
      score, and endoscopy findings. Abdominal images were reviewed by a radiologist
      (or a hepatologist trained by a radiologist) and searched for the presence of
      SPSS, defined as spontaneous communications between the portal venous system or
      splanchnic veins and the systemic venous system, excluding gastroesophageal
      varices. Patients were assigned to groups with large SPSS (L-SPSS, >=8 mm), small
      SPSS (S-SPSS, <8 mm), or without SPSS (W-SPSS). The main outcomes were the
      incidence of complications of cirrhosis and mortality according to the presence
      of SPSS. Secondary measurements were the prevalence of SPSS in patients with
      cirrhosis and their radiologic features. RESULTS: L-SPSS were identified in 488
      (28%) patients, S-SPSS in 548 (32%) patients, and no shunt (W-SPSS) in 693 (40%)
      patients. The most common L-SPSS was splenorenal (46% of L-SPSS). The presence
      and size of SPSS increased with liver dysfunction: among patients with MELD
      scores of 6-9, 14% had L-SPSS and 28% had S-SPSS; among patients with MELD scores
      of 10-13, 30% had L-SPSS and 34% had S-SPSS; among patients with MELD scores of
      14 or higher, 40% had L-SPSS and 32% had S-SPSS (P < .001 for multiple comparison
      among MELD groups). HE was reported in 48% of patients with L-SPSS, 34% of
      patients with S-SPSS, and 20% of patients W-SPSS (P < .001 for multiple
      comparison among SPSS groups). Recurrent or persistent HE was reported in 52% of
      patients with L-SPSS, 44% of patients with S-SPSS, and 37% of patients W-SPSS (P
      = .007 for multiple comparison among SPSS groups). Patients with SPSS also had a
      larger number of portal hypertension-related complications (bleeding or ascites)
      than those W-SPSS. Quality of life and transplantation-free survival were lower
      in patients with SPSS vs without. SPSS were an independent factor associated with
      death or liver transplantation (hazard ratio, 1.26; 95% confidence interval, 1.06
      1.49) (P = .008) in multivariate analysis. When patients were stratified by MELD
      score, SPSS were associated with HE independently of liver function: among
      patients with MELD scores of 6-9, HE was reported in 23% with L-SPSS, 12% with S
      SPSS, and 5% with W-SPSS (P < .001 for multiple comparison among SPSS groups);
      among those with MELD scores of 10-13, HE was reported in 48% with L-SPSS, 33%
      with S-SPSS, and 23% with W-SPSS (P < .001 for multiple comparison among SPSS
      groups); among patients with MELD scores of 14 or more, HE was reported in 59%
      with L-SPSS, 57% with S-SPSS, and 48% with W-SPSS (P = .043 for multiple
      comparison among SPSS groups). Patients with SPSS and MELD scores of 6-9 were at
      higher risk for ascites (40.5% vs 23%; P < .001) and bleeding (15% vs 9%; P =
      .038) than patients W-SPSS and had lower odds of transplant-free survival (hazard
      ratio 1.71; 95% confidence interval, 1.16-2.51) (P = .006). CONCLUSIONS: In a
      retrospective analysis of almost 2000 patients, we found 60% to have SPSS;
      prevalence increases with deterioration of liver function. SPSS increase risk for
      HE and with a chronic course. In patients with preserved liver function, SPSS
      increase risk for complications and death. ClinicalTrials.gov ID NCT02692430.

PMID- 29360463
TI  - Ceragenin CSA13 Reduces Clostridium difficile Infection in Mice by Modulating the
      Intestinal Microbiome and Metabolites.
AB  - BACKGROUND & AIMS: Clostridium difficile induces intestinal inflammation by
      releasing toxins A and B. The antimicrobial compound cationic steroid
      antimicrobial 13 (CSA13) has been developed for treating gastrointestinal
      infections. The CSA13-Eudragit formulation can be given orally and releases CSA13
      in the terminal ileum and colon. We investigated whether this form of CSA13
      reduces C difficile infection (CDI) in mice. METHODS: C57BL/6J mice were infected
      with C difficile on day 0, followed by subcutaneous administration of pure CSA13
      or oral administration of CSA13-Eudragit (10 mg/kg/d for 10 days). Some mice were
      given intraperitoneal vancomycin (50 mg/kg daily) on days 0-4 and relapse was
      measured after antibiotic withdrawal. The mice were monitored until day 20; colon
      and fecal samples were collected on day 3 for analysis. Blood samples were
      collected for flow cytometry analyses. Fecal pellets were collected each day from
      mice injected with CSA13 and analyzed by high-performance liquid chromatography
      or 16S sequencing; feces were also homogenized in phosphate-buffered saline and
      fed to mice with CDI via gavage. RESULTS: CDI of mice caused 60% mortality,
      significant bodyweight loss, and colonic damage 3 days after infection; these
      events were prevented by subcutaneous injection of CSA13 or oral administration
      CSA13-Eudragit. There was reduced relapse of CDI after administration of CSA13
      was stopped. Levels of CSA13 in feces from mice given CSA13-Eudragit were
      significantly higher than those of mice given subcutaneous CSA13. Subcutaneous
      and oral CSA13 each significantly increased the abundance of
      Peptostreptococcaceae bacteria and reduced the abundance of C difficile in fecal
      samples of mice. When feces from mice with CDI and given CSA13 were fed to mice
      with CDI that had not received CSA13, the recipient mice had significantly
      increased rates of survival. CSA13 reduced fecal levels of inflammatory
      metabolites (endocannabinoids) and increased fecal levels of 4 protective
      metabolites (ie, citrulline, 3-aminoisobutyric acid, retinol, and ursodeoxycholic
      acid) in mice with CDI. Oral administration of these CSA13-dependent protective
      metabolites reduced the severity of CDI. CONCLUSIONS: In studies of mice, we
      found the CSA13-Eudragit formulation to be effective in eradicating CDI by
      modulating the intestinal microbiota and metabolites.

PMID- 29360465
TI  - Neochamaejasmin A inhibits KV1.4 channel activity via direct binding to the pore.
AB  - Stellera chamaejasme L. (Thymelaeaceae) is a toxic perennial herb and widespread
      in Mongolia and the northern parts of China. Previous studies have revealed that
      Neochamaejasmin A (NCA), one of the main active ingredients in the plant roots,
      has many bioactivities such as inhibiting the P-gp-mediated efflux. But whether
      NCA affects ion channels is unknown. Here the whole cell patch clamp technique
      was used to investigate whether NCA affects ion channels, especially how it
      inhibits KV1.4. Mutagenesis and structure-based molecular simulation were used
      for analysis of inhibition mechanism and identification of binding site. Among
      all the channels assayed, KV1.4 stood out as the one on which NCA showed
      strongest inhibition activity with IC50 of 7.55 uM. Compared with NCA's
      isomerides, neochamaejasmin B (NCB) and chamaechromone (CMC), NCA also exhibited
      superior inhibition ability on KV1.4. Three mutations, V549A, A553V and V560A,
      occurred inside the pore, were found to significantly alleviate the NCA blocking
      effects, suggesting that they are the important binding sites of NCA. Structure
      based modelling showed that the phenolic hydroxyl group of NCA can form hydrogen
      bonds with main chains of Val549 and Ala553 in IS6 and IVS6 segment respectively,
      which support our in vitro results. In conclusion, data suggest that NCA might
      inhibit KV1.4 channels via direct binding to the pore domain.

PMID- 29360464
TI  - Molecular characterization of feline melanocortin 4 receptor and melanocortin 2
      receptor accessory protein 2.
AB  - Melanocortin 4 receptor (MC4R), which is a member of the G protein-coupled
      receptor (GPCR) family, mediates regulation of energy homeostasis upon the
      binding of alpha-melanocyte-stimulating hormone (alpha-MSH) in the central
      nervous system (CNS). Melanocortin 2 receptor accessory protein 2 (MRAP2)
      modulates the function of MC4R. We performed cDNA cloning of cat MC4R and MRAP2
      and characterized their amino acid sequences, mRNA expression patterns in cat
      tissues, protein-protein interactions, and functions. We found high sequence
      homology (>88%) with other mammalian MC4R and MRAP2 encoding 332 and 206 amino
      acid residues, respectively. Reverse transcription-polymerase chain reaction
      analysis revealed that cat MC4R and MRAP2 mRNA were expressed highly in the CNS.
      In CHO-K1 cells transfected with cat MC4R, stimulation with alpha-MSH increased
      intracellular cyclic adenosine monophosphate (cAMP) concentration in a dose
      dependent manner. Furthermore, the presence of MRAP2 enhanced the cat MC4R
      mediated cAMP production. These results suggested that cat MC4R acts as a
      neuronal mediator in the CNS and that its function is modulated by MRAP2. In
      addition, our NanoBiT study showed the dynamics of their interactions in living
      cells; stimulation with alpha-MSH slightly affected the interaction between MC4R
      and MRAP2, and did not affect MC4R homodimerization, suggesting that they
      interact in the basal state and that structural change of MC4R by activation may
      affect the interaction between MC4R and MRAP2.

PMID- 29360466
TI  - Enteric nervous system manifestations of neurodegenerative disease.
AB  - Neurological disorders cause gastrointestinal (GI) symptoms that are debilitating
      and markedly diminish quality of life in patients. The enteric nervous system
      (ENS), the intrinsic nervous system of the GI tract that is often referred to as
      "the second brain", shares many features with the central nervous system. The ENS
      plays an essential role in regulating many GI functions including motility and
      fluid secretion. Enteric neuronal degeneration could therefore be responsible for
      the GI symptoms commonly observed in neurological conditions. Here we describe
      the organization and functions of the ENS and then review the evidence for ENS
      involvement in two common neurodegenerative disorders, Parkinson's disease (PD)
      and Alzheimer's disease (AD). Data from patients as well as animal models suggest
      that PD affects distinct subsets of neurons and glia in the ENS, and that the ENS
      may participate in the pathogenesis of this disorder. While there has been great
      enthusiasm for the possibility of sampling the ENS for diagnosis or therapeutic
      monitoring of PD, further work is needed to determine which enteric neurons are
      most affected and how ENS function could be modulated to ameliorate GI symptoms
      in patients. Although AD is far more common than PD and AD patients also
      experience GI symptoms, understanding of ENS dysfunction in AD is in its infancy.
      Much work remains to be done in both of these fields to determine how the ENS
      contributes to and/or is altered by these disorders, and how to target the ENS
      for more effective treatment of GI comorbidities.

PMID- 29360468
TI  - Gut-immune-brain dysfunction in Autism: Importance of sex.
AB  - Autism Spectrum Disorder (ASD) is characterized by social behavior deficits,
      stereotypies, cognitive rigidity, and in some cases severe intellectual
      impairment and developmental delay. Although ASD is most widely identified by its
      neurological deficits, gastrointestinal issues are common in ASD. An intimate and
      complex relationship exists between the gut, the immune system, and the brain,
      leading to the hypothesis that ASD may be a systems-level disease affecting the
      gut and immune systems, in addition to the brain. Despite significant advances in
      understanding the contribution of the gut and immune systems to the etiology of
      ASD, there is an intriguing commonality among patients that is not well
      understood: they are predominantly male. Virtually no attention has been given to
      the potential role of sex-specific regulation of gut, peripheral, and central
      immune function in ASD, despite the 4:1 male-to-female bias in this disorder. In
      this review, we discuss recent revelations regarding the impact of gut-immune
      brain relationships on social behavior in rodent models and in ASD patients,
      placing them in the context of known or putative sex specific mechanisms.

PMID- 29360467
TI  - Parkinson's disease from the gut.
AB  - Parkinson's disease (PD) is a debilitating neurodegenerative condition associated
      with tremor, rigidity, dementia, and gastrointestinal symptoms such as
      constipation, nausea and vomiting. The pathological hallmarks of PD are Lewy
      bodies and neurites in the brain and peripheral nerves. The major constituent of
      Lewy bodies is the neuronal protein alpha-synuclein. Misfolding of alpha
      synuclein confers prion-like properties enabling its spread from cell to cell.
      Misfolded alpha-synuclein also serves as a template and induces misfolding of
      endogenous alpha-synuclein in recipient cells leading to the formation of
      oligomers that progress to fibrils and eventually Lewy bodies. Accumulating
      evidence suggests that PD may arise in the gut. Clinically, gastrointestinal
      symptoms often appear in patients before other neurological signs and aggregates
      of alpha-synuclein have been found in enteric nerves of PD patients. Importantly,
      patients undergoing vagotomy have a reduced risk of developing PD.
      Experimentally, abnormal forms of alpha-synuclein appear in enteric nerves before
      they appear in the brain and injection of abnormal alpha-synuclein into the wall
      of the intestine spreads to the vagus nerve. Ingested toxins and alterations in
      gut microbiota can induce alpha-synuclein aggregation and PD, however, it is not
      known how PD starts. Recently, it has been shown that sensory cells of the gut
      known as enteroendocrine cells (EECs) contain alpha-synuclein and synapse with
      enteric nerves, thus providing a connection from the gut to the brain. It is
      possible that abnormal alpha-synuclein first develops in EECs and spreads to the
      nervous system.

PMID- 29360469
TI  - Gut bacteria interaction with vagal afferents.
AB  - Contemporary techniques including the use of germ-free models and next generation
      sequencing have deepened our understanding of the gut microbiota dynamics and its
      influence on host physiology. There is accumulating evidence that the gut
      microbiota can communicate to the CNS and is involved in the development of
      metabolic and behavioral disorders. Vagal afferent terminals are positioned
      beneath the gut epithelium where they can receive, directly or indirectly,
      signals produced by the gut microbiota, to affect host behavior, including
      feeding behavior. Supplementation with L. Rhamnosus in mice notably causes a
      decrease in anxiety and these effects are abolished by vagotomy. Additionally,
      chronic treatment with bacterial byproduct lipopolysaccharide (LPS) blunts
      vagally-mediated post-ingestive feedback and is associated with increased food
      intake. Inflammation in the nodose ganglion (NG), the location of vagal afferent
      neurons' cell bodies, may be a key triggering factor of microbiota-driven vagal
      alteration. Interestingly, several models show that vagal damage leads to an
      increase in immune cell (microglia) activation in the NG and remodeling of the
      vagal pathway. Similarly, diet-driven microbiota dysbiosis is associated with NG
      microglia activation and decreased vagal outputs to the CNS. Crucially,
      preventing dysbiosis and microglia activation in high-fat diet fed rodents
      normalizes vagal innervation and energy intake, highlighting the importance of
      microbiota/vagal communication in controlling feeding behavior. As of today, new
      consideration of potential roles for glial influence on vagal communication and
      new methods of vagal afferent ablation open opportunities to increase our
      understanding of how the gut microbiota influence its host's health and behavior.

PMID- 29360470
TI  - CDK5RAP2 gene and tau pathophysiology in late-onset sporadic Alzheimer's disease.
AB  - INTRODUCTION: Because currently known Alzheimer's disease (AD) single-nucleotide
      polymorphisms only account for a small fraction of the genetic variance in this
      disease, there is a need to identify new variants associated with AD. METHODS:
      Our team performed a genome-wide association study in the Quebec Founder
      Population isolate to identify novel protective or risk genetic factors for late
      onset sporadic AD and examined the impact of these variants on gene expression
      and AD pathology. RESULTS: The rs10984186 variant is associated with an increased
      risk of developing AD and with a higher CDK5RAP2 mRNA prevalence in the
      hippocampus. On the other hand, the rs4837766 variant, which is among the best
      cis-expression quantitative trait loci in the CDK5RAP2 gene, is associated with
      lower mild cognitive impairment/AD risk and conversion rate. DISCUSSION: The
      rs10984186 risk and rs4837766 protective polymorphic variants of the CDK5RAP2
      gene might act as potent genetic modifiers for AD risk and/or conversion by
      modulating the expression of this gene.

PMID- 29360471
TI  - High-titer antibody depletion enhances discovery of diverse serum antibody
      specificities.
AB  - The human antibody repertoire is a unique repository of information regarding
      infection, inflammation, and autoimmunity of the past, present, and future.
      However, antibodies can span vast ranges of concentrations with varying
      affinities and the repertoire is often heavily polarized by a few species. These
      complexities lead to difficulties detecting and characterizing low abundance
      antibody species that may be relevant to disease. We therefore developed a method
      to selectively remove antibodies from a sample in proportion to the titer of the
      species prior to analysis, referred to as high-titer depletion (HTD). Peptides
      from a large random peptide display library were enriched towards binding high
      titer antibody species and utilized as binding reagents to deplete the
      corresponding species from the specimen. HTD enabled the discovery of antibody
      binding specificities using random peptide library screening with reduced cross
      reactivity and background signal and improved coverage of low abundance species.
      With HTD, three monoclonal antibody species were detected at concentrations at
      least an order of magnitude lower than without HTD. Additionally, 92 serum
      antibody specificities were readily discovered from an individual specimen using
      HTD compared to only 25 specificities without HTD. Parameters affecting the
      extent of depletion such as the concentration of depleted serum were also
      adjusted to reproducibly improve the coverage of antibody specificities. These
      results demonstrate that HTD could be employed for the discovery of rare
      specificities related to disease and enable extensive characterization of the
      antibody repertoire. Moreover, the strategy of depletion in proportion to titer
      could be extended to other applications with complex biological samples to
      improve discovery.

PMID- 29360472
TI  - Same critical features are used for identification of familiarized and unfamiliar
      faces.
AB  - Many studies have shown better recognition for faces we have greater experience
      with, relative to unfamiliar faces. However, it is still not clear if and how the
      representation of faces changes during the process of familiarization. In a
      previous study, we discovered a subset of facial features, for which we have high
      perceptual sensitivity (PS), that were critical for determining the identity of
      unfamiliar faces. This was done by assigning values to 20 different facial
      features based on perceptual rating, converting faces into feature-vectors, and
      measuring the correlations between face similarity ratings and distances between
      feature-vectors. In the current study, we examined the contribution of high and
      low-PS features to face identity after familiarization. To familiarize
      participants with unfamiliar faces, we used an individuation training protocol
      that was found to be effective in previous studies, in which different names are
      assigned to different faces and participants are asked to learn the face-name
      association. Our findings show that even after repeated exposure to the same
      image of each identity, which allows close examination of all facial features,
      only high-PS features contributed to face identity, while low-PS features did
      not. This subset of high-PS features includes both internal and external features
      and part and configuration features. We therefore conclude that identification of
      familiarized and unfamiliar faces may rely on the same subset of critical
      features. These findings further support a new categorization of facial features
      according to their perceptual sensitivity.

PMID- 29360473
TI  - The adult face-diet: A naturalistic observation study.
AB  - Experience plays a fundamental role in the development of visual function.
      Exposure to different types of faces is an important factor believed to shape
      face perception ability. Contents of daily exposure to faces, i.e., the face
      diet, of infants have been documented in previous studies. While face perception
      involves a protracted development and continues to be malleable well into
      adulthood, an empirical study of the adult face-diet has been lacking. We
      collected first-person perspective footage from 30 adults during the course of
      their daily activities. We found that adults' exposure to faces is longer and
      more diverse compared to that of infants. Frequency of exposure were highest for
      familiar (75%), own-race (81%), and three-quarter pose (44%) faces. Faces in the
      adult face-diet were relatively large (median 6 degrees ) suggesting fairly close
      viewing distances. Face sizes were significantly larger for familiar (median 7.1
      degrees ) compared to unfamiliar (median 4.9 degrees ) faces, reflecting the
      closer viewing distances that characterize social interaction. These results are
      consistent with the view that face recognition processes are tuned to the
      ecologically relevant values of face attributes that are encountered most
      frequently in the real-life context to optimize face perception abilities.

PMID- 29360474
TI  - A novel flavanone derivative inhibits dengue virus fusion and infectivity.
AB  - Dengue infection is a global burden affecting millions of world population.
      Previous studies indicated that flavanones were potential dengue virus
      inhibitors. We discovered that a novel flavanone derivative, 5-hydroxy-7-methoxy
      6-methylflavanone (FN5Y), inhibited DENV2 pH-dependent fusion in cell-based
      system with strong binding efficiency to DENV envelope protein at K (P83, L107,
      K128, L198), K' (T48, E49, A50, L198, Q200, L277), X' (Y138, V354, I357), and Y'
      (V97, R99, N103, K246) by molecular dynamic simulation. FN5Y inhibited DENV2
      infectivity with EC50s (and selectivity index) of 15.99 +/- 5.38 (>6.25), and
      12.31 +/- 1.64 (2.23) MUM in LLC/MK2 and Vero cell lines, respectively, and
      inhibited DENV4 at 11.70 +/- 6.04 (>8.55) MUM. CC50s in LLC/MK2, HEK-293, and
      HepG2 cell lines at 72 h were higher than 100 MUM. Time-of-addition study
      revealed that the maximal efficacy was achieved at early after infection
      corresponded with pH-dependent fusion. Inactivating the viral particle,
      interfering with cellular receptors, inhibiting viral protease, or the virus
      replication complex were not major targets of this compound. FN5Y could become a
      potent anti-flaviviral drug and can be structurally modified for higher potency
      using simulation to DENV envelope as a molecular target.

PMID- 29360475
TI  - Structure of the alexithymic brain: A parametric coordinate-based meta-analysis.
AB  - Alexithymia refers to deficiencies in identifying and expressing emotions. This
      might be related to changes in structural brain volumes, but its neuroanatomical
      basis remains uncertain as studies have shown heterogeneous findings. Therefore,
      we conducted a parametric coordinate-based meta-analysis. We identified seventeen
      structural neuroimaging studies (including a total of 2586 individuals with
      different levels of alexithymia) investigating the association between gray
      matter volume and alexithymia. Volumes of the left insula, left amygdala, orbital
      frontal cortex and striatum were consistently smaller in people with high levels
      of alexithymia. These areas are important for emotion perception and emotional
      experience. Smaller volumes in these areas might lead to deficiencies in
      appropriately identifying and expressing emotions. These findings provide the
      first quantitative integration of results pertaining to the structural
      neuroanatomical basis of alexithymia.

PMID- 29360476
TI  - Terminology matters: There is no targeting, but retention.

PMID- 29360477
TI  - Peritoneal dialysis beyond kidney failure?
AB  - Compared to extracorporeal modalities, peritoneal dialysis (PD) is less invasive
      and more cost-effective, wherein blood is dialyzed intra-corporeally against a
      solution instilled in the peritoneal cavity. Although PD is mainly indicated for
      patients with end-stage renal failure, it has also been used for several non
      renal indications. The aim of this review is to provide an overview of the role
      of PD beyond kidney failure. The alternative indications of PD include
      hypothermia, congestive heart failure, hyperammonemia and poisoning with
      xenobiotics. The use of PD as a treatment for acute pancreatitis and psoriasis
      was initially proposed but could not be established; these indications are
      therefore classified as historically relevant. Recent developments have led to a
      potential application of PD during the management of stroke and as an oxygenation
      therapy with the use of oxygen carriers. Novel colloid-based dialysates with
      improved functionality with respect to detoxification and oxygenation are
      currently underway, though their efficacy has so far only been demonstrated in
      pre-clinical settings. Finally, insight into potential future developments of PD
      is given. Characterization studies are proposed to better understand the fate of
      non-recovered carriers following dialysate removal, their efficacy following
      multiple administrations and potential immune response to optimize their
      formulation, enabling their clinical translation.

PMID- 29360478
TI  - Bioorthogonal strategies for site-directed decoration of biomaterials with
      therapeutic proteins.
AB  - Emerging strategies targeting site-specific protein modifications allow for
      unprecedented selectivity, fast kinetics and mild reaction conditions with high
      yield. These advances open exciting novel possibilities for the effective
      bioorthogonal decoration of biomaterials with therapeutic proteins. Site
      specificity is particularly important to the therapeutics' end and translated by
      targeting specific functional groups or introducing new functional groups into
      the therapeutic at predefined positions. Biomimetic strategies are designed for
      modification of therapeutics emulating enzymatic strategies found in Nature.
      These strategies are suitable for a diverse range of applications - not only for
      protein-polymer conjugation, particle decoration and surface immobilization, but
      also for the decoration of complex biomaterials and the synthesis of
      bioresponsive drug delivery systems. This article reviews latest chemical and
      enzymatic strategies for the biorthogonal decoration of biomaterials with
      therapeutic proteins and inter-positioned linker structures. Finally, the
      numerous reports at the interface of biomaterials, linkers, and therapeutic
      protein decoration are integrated into practical advice for design considerations
      intended to support the selection of productive ligation strategies.

PMID- 29360479
TI  - Screening of quorum sensing peptides for biological effects in neuronal cells.
AB  - Quorum sensing peptides (QSP) are an important class of bacterial peptides which
      can have an effect on human host cells. These peptides are used by bacteria to
      communicate with each other. Some QSP are able to cross the blood-brain barrier
      and reach the brain parenchyma. However, nothing is known about the effects of
      these peptides in the brain. Therefore, 85 quorum sensing peptides were screened
      on six different neuronal cell lines using MTT toxicity, neurite differentiation,
      cytokine production and morphology as biological outcomes. This primary screening
      resulted in 22 peptides with effects observed on neuronal cell lines, indicating
      a possible role in the gut-brain axis. Four peptides (Q138, Q143, Q180 and Q212)
      showed induction of neurite outgrowth while two peptides (Q162 and Q208)
      inhibited NGF-induced neurite outgrowth in PC12 cells. Eight peptides (Q25, Q135,
      Q137, Q146, Q151, Q165, Q208 and Q298) induced neurite outgrowth in human SH-SY5Y
      neuroblastoma cells. Two peptides (Q13 and Q52) were toxic for SH-SY5Y cells and
      one (Q123) for BV-2 microglia cells based on the MTT assay. Six peptides had an
      effect on BV-2 microglia, Q180, Q184 and Q191 were able to induce IL-6 expression
      and Q164, Q192 and Q208 induced NO production. Finally, Q75 and Q147 treated
      C8D1A astrocytes demonstrated a higher fraction of round cells. Overall, these in
      vitro screening study results indicate for the first time possible effects of QSP
      on neuronal cells.

PMID- 29360480
TI  - Regular physical activity eliminates the harmful association of television
      watching with multimorbidity. A cross-sectional study from the European Social
      Survey.
AB  - The aims of the study were to analyse the association of television viewing,
      physical activity (PA), and multimorbidity; and to understand if PA attenuates or
      eliminates the detrimental associations between television viewing and
      multimorbidity. This is a cross-sectional study based on data from the European
      Social Survey round 7, 2014. Participants were 32,931 adults (15,784 men), aged
      18-114 years old, from 18 European countries. Self-reported information regarding
      chronic diseases (CD), PA and time watching television were collected through
      interview. Logistic regression analysis was conducted to analyse the association
      between watching television and PA with the presence of multimorbidity (>=1 CD).
      Men and women who watched television had increased odds of having multimorbidity.
      When considering PA it was observed that, independently of television viewing,
      compared to engaging in PA for <=1 day/week, engaging in 2-4 days/week and in >=5
      days/week was inversely associated with multimorbidity. Increased odds of
      multimorbidity were observed for men spending >3 h/day watching television in the
      2-3 days/week and <=1 day/week categories of PA. For women engaged in 30 min of
      physical activity 2-3 days/week, spending >3 h/day watching television was
      associated with higher odds for multimorbidity. For adults who practiced physical
      activity on >= 5 days/week watching television was not associated with
      multimorbidity. Time spent watching television is associated with multimorbidity.
      However, physical activity participation can attenuate or even eliminate this
      association.

PMID- 29360481
TI  - Documentation of e-cigarette use and associations with smoking from 2012 to 2015
      in an integrated healthcare delivery system.
AB  - It is unclear whether use of electronic nicotine delivery systems (ENDS) precedes
      cigarette smoking initiation, relapse, and/or quitting. Healthcare systems with
      electronic health records (EHRs) provide unique data to examine ENDS use and
      changes in smoking. We examined the incidence of ENDS use (2012-2015) based on
      clinician documentation and tested whether EHR documented ENDS use is associated
      with twelve-month changes in patient smoking status using a matched retrospective
      cohort design. The sample was Kaiser Permanente Northern California (KPNC)
      patients aged >=12 with documented ENDS use (N = 7926); 57% were current smokers,
      35% former smokers, and 8% never-smokers. ENDS documentation incidence peaked in
      2014 for current and former smokers and in 2015 for never-smokers. We matched
      patients with documented ENDS use to KPNC patients without documented ENDS use (N
      = 7926) on age, sex, race/ethnicity, and smoking status. Documented ENDS use
      predicted the likelihood of smoking in the following year. Among current smokers,
      ENDS use was associated with greater odds of quitting smoking (OR = 1.17, 95%CI =
      1.05-1.31). Among former smokers, ENDS use was associated with greater odds of
      smoking relapse (OR = 1.53, 95%CI = 1.22-1.92). Among never-smokers, ENDS use was
      associated with greater odds of initiating smoking (OR = 7.41, 95%CI = 3.14
      17.5). The overall number of current smokers at 12 months was slightly higher
      among patients with (N = 3931) versus without (N = 3850) documented ENDS use.
      Results support both potential harm reduction of ENDS use (quitting combustibles
      among current smokers) and potential for harm (relapse to combustibles among
      former smokers, initiation for never-smokers).

PMID- 29360482
TI  - Biomonitoring Equivalents for interpretation of urinary iodine.
AB  - Iodine is an essential nutrient whose deficiency or excess exposure can cause
      adverse health effects. The primary sources of iodine exposure in the general
      population are iodized salt, dairy products, bread and sea food. Urinary iodine
      concentrations (UIC) have been measured by Canadian Health Measures Survey (CHMS)
      and US National Health and Nutrition Examination Survey (NHANES). The Institute
      of Medicine (IOM), the US Agency for Toxic Substances and Disease Registry
      (ATSDR) and World Health Organization (WHO) have established exposure guidance
      values for nutrition (IOM Estimated Average Requirement (EAR), Recommended
      Dietary Allowance (RDA), WHO Recommended Nutrient Intake (RNI)) and toxicity (IOM
      Tolerable Upper Intake Level (UL); ATSDR Minimal Risk Level (MRL), WHO
      International Programme on Chemical Safety (IPCS) Tolerable Daily Intake (TDI)).
      Using a urinary excretion fraction of 0.9, Biomonitoring Equivalents (BE) for the
      EAR, RDA, UL and MRL were derived for adults (60, 100, 730 and 450 MUg/L,
      respectively) and children (50, 80, 580 and 360 MUg/L, respectively). The
      population median UIC values from NHANES and CHMS for adults (140-181, 122-126
      MUg/L, respectively) and children (232, 189 MUg/L, respectively) were above the
      criteria for assessing iodine nutrition, indicating that US and Canadian
      populations are likely to have adequate population iodine nutrition. The median
      UIC from NHANES and CHMS do not exceed BE values derived from exposure guidance
      values for toxicity.

PMID- 29360483
TI  - Toxicity assessment of the extractables from multi-layer coextrusion poly
      ethylene bags exposed to pH=5 solution containing 4% benzyl alcohol and 0.1 M
      sodium acetate.
AB  - A non-target analysis was developed for the analysis of extractables from multi
      layer coextrusion bags exposed to 4% benzyl alcohol solution and 0.1 M sodium
      acetate at pH = 5 for defined periods (15 day, 45 day and 90 day) according to
      manufacturer instructions based on the ultra-performance liquid chromatography
      (UPLC) quadrupole-time of flight mass spectrometry (Q-TOF MS). In order to
      confirm the extractables, principal component analysis (PCA) was used to indicate
      the differences among samples of different periods. Then, the extractables were
      identified based on searching the self-built library or online searching. The
      total content of extractables of 90 day samples was 589.78 MUg/L, and the content
      was in the range of acceptable levels for pharmaceutical manufacturers. The risk
      assessment of the extractables were evaluated by Toxtree and T.E.S.T. software to
      avoid the animals bioexperiment.

PMID- 29360484
TI  - Cancer-Associated Long Noncoding RNA SMRT-2 Controls Epidermal Differentiation.

PMID- 29360485
TI  - Development of a Clinically Relevant Men's Health Phenotype and Correlation of
      Systemic and Urologic Conditions.
AB  - OBJECTIVE: To develop a clinically relevant men's health phenotype and
      investigate the correlation between severity of urologic symptoms and systemic
      health conditions METHODS: Retrospective chart review was performed for men
      seeking care for benign prostatic hypertrophy, erectile dysfunction or chronic
      prostatitis or chronic pelvic pain syndrome. Urologic symptoms were assessed with
      the International Prostate Symptom Score, Sexual Health Inventory for Men, and
      National Institute of Health Chronic Prostatitis Symptom Score. Each was graded
      as absent or mild (0), moderate (1), or severe (2) and totaled for a urologic
      score (US). Seven comorbidities with known impact on urologic symptoms were
      similarly graded (0-2 for each) and totaled for a systemic score (SS). These
      domains were anxiety, cardiovascular, testosterone deficiency, insulin
      (diabetes), obesity, neurologic, and sleep apnea. RESULTS: The study included 415
      men with median age of 53.8 (range 19-92). Mean total US was 2.1 (range 0-6) and
      mean SS was 4.1 (0-12). There was a strong correlation between US and SS
      (Spearman Rho = 0.37, P < .00001) which was consistent regardless of age. The
      hierarchy of systemic condition impact on US was cardiovascular> neurologic>
      diabetes> anxiety> sleep apnea> obesity> testosterone. By cluster analysis the
      tightest correlations were age with cardiovascular, anxiety with CPPS, and
      diabetes with erectile dysfunction. CONCLUSION: Systemic health conditions
      correlate strongly with urologic symptoms in men who present for urologic care.
      Phenotyping with ACTIONS (anxiety, cardiovascular, testosterone deficiency,
      insulin, obesity, neurologic, sleep apnea) can identify modifiable conditions
      that may impact urologic symptoms and outcome of interventions. Future validation
      in the general population is needed.

PMID- 29360486
TI  - Application of Prepuncture on the Double-tract Percutaneous Nephrolithotomy Under
      Ultrasound Guidance for Renal Staghorn Calculi: First Experience.
AB  - OBJECTIVE: To evaluate the effect of prepuncture on the double-tract percutaneous
      nephrolithotomy (PCNL) under ultrasound guidance for renal staghorn calculi.
      METHOD: Double-tract or even multi-tract is necessary for the treatment of
      staghorn calculi. However, intraoperative injury, exudation, bleeding, and
      influence of original tract might lead to difficulty in second puncture, thus
      prolonging operating time, and even lead to puncture failure. We retrospectively
      reviewed the records of 178 patients with renal staghorn calculi who received
      double-tract PCNL in our department. Sixty-three patients received non
      prepuncture double-tract PCNL (group A) and 115 patients underwent prepuncture
      double-tract PCNL (group B). In group A, the second tract was established after
      failing to further fragment by the first tract. In group B, based on the
      preoperative computed tomography, intravenous pyelography, and intraoperative
      ultrasound images, 2 optimal punctual positions were set. The first guidewire was
      manipulated in the pelvicalyceal system after successful puncture. However, we
      routinely performed the other puncture and a preplaced second wire was put into
      the collecting system as a potential second tract. RESULTS: The mean operating
      time was longer in group A than that in group B (P = .033). There was no
      statistical difference between group A and group B in postoperative instant stone
      free rate and final stone-free rate. In the non-prepuncture double-tract PCNL
      group, blood transfusion rate was 7.9% (5/63) and it was only 1.7% (2/115) in the
      prepuncture double-tract PCNL group (P = .042). CONCLUSION: In the treatment of
      renal staghorn calculi, prepuncture double-tract PCNL can shorten operating time
      and reduce the occurrence of blood transfusion events. This new method might be
      worth generalizing.

PMID- 29360487
TI  - Development of an Sce-I mutagenesis system for Burkholderia cepacia complex
      strains.
AB  - The Burkholderia cepacia complex (Bcc) consists of at least 20 phenotypically
      similar but genotypically distinct Gram-negative bacteria that are ubiquitous in
      nature, are capable of promoting plant growth and biodegradation of pollutants,
      but that also are highly antibiotic resistant and produce damaging effects
      towards plants, fungi, and humans. To study these genetically recalcitrant
      bacteria in detail, molecular tools are required that work efficiently with the
      many strains and species of the Bcc. One mutagenesis strategy that has been used
      effectively to analyze the genes of Burkholderia cenocepacia is based upon the
      activity of the Sce-I restriction enzyme. Unfortunately, this system is limited
      in its applicability to many members of the Bcc. Therefore, we undertook the
      expansion of this system to create an Sce-I mutagenesis system that could be used
      with many different species and strains of the Bcc, including members of the B.
      cenocepacia IIIB Midwest clones. We demonstrated the use of this system by clean
      deleting the lipo-oligosaccharide (LOS) inner core biosynthesis gene waaC, to
      create a B. cenocepacia PC184 strain variant with truncated LOS. This enhanced
      mutagenesis system can be used to analyze a wide range of Burkholderia and other
      Gram-negative bacteria.

PMID- 29360488
TI  - Detection of carbapenemases with a newly developed commercial assay using Matrix
      Assisted Laser Desorption Ionization-Time of Flight.
AB  - This study evaluated the performance of the MBT STAR-Carba kit (Bruker
      Daltonics), to detect carbapenemase producing Enterobacteriaceae, Pseudomonas
      aeruginosa and Acinetobacter spp. in comparison with the RAPIDEC(r) CARBA NP test
      (BioMerieux). MBT STAR-Carba allowed the detection of carbapenemases in
      Enterobacteriaceae and P. aeruginosa.

PMID- 29360489
TI  - Voluntary exercise impact on cognitive impairments in sleep-deprived intact
      female rats.
AB  - Sleep loss is a common problem in modern societies affecting different aspects of
      individuals' lives. Many studies have reported that sleep deprivation (SD) leads
      to impairments in various types of learning and memory. Physical exercise has
      been suggested to attenuate the cognitive impairments induced by sleep
      deprivation in male rats. Our previous studies have shown that forced exercise by
      treadmill improved learning and memory impairments following SD. The aim of the
      current study was to investigate the effects of voluntary exercise by running
      wheel on cognitive, motor and anxiety-like behavior functions of female rats
      following 72 h SD. Intact female rats were used in the present study. The
      multiple platform method was applied for the induction of 72 h SD. The exercise
      protocol was 4 weeks of running wheel and the cognitive function was evaluated
      using Morris water maze (MWM), passive avoidance and novel object recognition
      tests. Open field test and measurement of plasma corticosterone level were
      performed for evaluation of anxiety-like behaviors. Motor balance evaluation was
      surveyed by rotarod test. In this study, remarkable learning and long-term memory
      impairments were observed in sleep deprived rats in comparison to the other
      groups. Running wheel exercise ameliorated the SD-induced learning and memory
      impairments. Voluntary and mandatory locomotion and balance situation were not
      statistically significant among the different groups. Our study confirmed the
      negative effects of SD on cognitive function and approved protective effects of
      voluntary exercise on these negative effects.

PMID- 29360490
TI  - Diazepam fails to alter anxiety-like responses but affects motor function in a
      white-black test paradigm in larval zebrafish (Danio rerio).
AB  - The growing popularity of zebrafish in psychopharmacology and behavioral brain
      research is partly due to the practicality and simplicity of drug administration
      in this species. Several drugs may be administered to zebrafish by immersing the
      fish in the drug solution. Furthermore, numerous drugs developed for mammals,
      including humans, have been found to show a similar effect profile in the
      zebrafish. Thus, the zebrafish has been suggested as a potentially useful animal
      screening tool. Despite decades of drug development, anxiety still represents a
      major unmet medical need, and the search for anxiolytic compounds is continuing.
      The zebrafish has been proposed for high throughput screens for anxiolytic
      compounds, and the effects of anxiolytic compounds on the behavior of zebrafish
      have started to be explored. Diazepam (Valium(r)) is a frequently prescribed
      human anxiolytic, a GABAA receptor agonist, has also started to be tested in
      zebrafish, but with occasional contradicting results. Here, we investigate the
      effects of diazepam in larval (6-day post-fertilization old) zebrafish in a black
      white preference paradigm. We found significant white preference and thigmotaxis
      (edge preference) in our control fish, anxiety-like responses that habituated
      over time. However, unexpectedly, we observed no anxiolytic effects of diazepam
      on these behaviors, and only detected significant motor activity reducing effect
      of the drug. We discuss the complex interpretation of light/dark tests in
      zebrafish, and also speculate about the possibility of differential GABAergic
      mechanisms that diazepam affects in larval vs adult zebrafish.

PMID- 29360491
TI  - Long-term implant performance and patients' satisfaction in oligodontia.
AB  - OBJECTIVES: To assess long-term (>=10 years) implant survival, peri-implant
      health, patients' satisfaction and oral health related quality of life (OHQoL) in
      oligodontia patients rehabilitated with implant-based fixed prosthodontics.
      METHODS: All oligodontia patients treated >=10 years previously with implant
      based fixed prosthodontics at the University Medical Center Groningen, The
      Netherlands, were approached to participate. Clinical (plaque index, bleeding
      index, pocket probing depth) and radiographic (marginal bone level) data were
      collected between February and May 2016. Surgical implant details (e.g., bone
      augmentation) and implant loss were recalled from the medical records. Patients
      completed a satisfaction questionnaire (maximum score 10, high score favourable
      satisfaction) and the Oral Health Impact Profile (OHIP-NL49, maximum score 196,
      low score favourable satisfaction) to rate OHQoL. Implant survival was expressed
      according to Kaplan Meier. The Mann-Whitney U Test was used for the other
      analyses. RESULTS: Forty-one patients had been treated with implant-based fixed
      prosthodontics (n = 258) >=10 years previously. Cumulative 10-year implant
      survival of these 41 patients was 89.1% (95%CI 85.2-93.0%). Twenty-eight of them
      (n = 163 implants) were willing to visit us for additional clinical and
      radiographic assessments. In these 28 patients, highest peri-implant bone loss
      was observed for implants placed in augmented bone (p < 0.001). Peri-implant
      mucositis (65.4%) and peri-implantitis (16.1%) were rather common. Patients'
      satisfaction (8.3 +/- 1.5) and OHIP-NL49 scores (32.6 +/- 30.1) were favourable
      and not associated with number of agenetic teeth (<=10 versus >10). CONCLUSIONS:
      Long-term survival, satisfaction and OHQoL results reveal that implant treatment
      is a predictable and satisfactory treatment modality for oligodontia, although
      peri-implant mucositis and peri-implantitis are common. CLINICAL SIGNIFICANCE:
      This study showed unique long-term (>=10 years) results about implant survival,
      peri-implant health, patients' satisfaction and OHQoL in oligodontia patients
      rehabilitated with implant-based fixed prosthodontics.

PMID- 29360492
TI  - A randomised controlled study on the use of finishing and polishing systems on
      different resin composites using 3D contact optical profilometry and scanning
      electron microscopy.
AB  - OBJECTIVES: The aim of this study was to evaluate theeffects of different
      finishing and polishing techniques on the surface roughness of microhybrid and
      nanofilled resin composites. METHODS: The resin composites included were Filtek
      Z250 (a universal microhybrid resin composite) and Filtek Supreme XTE (a
      universal nanofill resin composite). Ninety cylindrical-shaped specimens were
      prepared for each composite resin material. The polishing methods used included
      tungsten carbide bur (TC); diamond bur (Db); Sof-Lex discs (S); Enhance PoGo
      discs (PG); TC + S; Db + S; TC + PG; Db + PG. Polymerisation against a Mylar
      strip without finishing and polishing acted as the control group. Surface
      roughness was measured using a 3D contact optical profilometer and surface
      morphology was examined by scanning electron microscope examination. RESULTS: The
      results showed that the Mylar-formed surfaces were smoothest for both composites.
      Finishing with the 20 MUm diamond finishing bur caused significantly greater
      surface irregularity (P < 0.0001) and damage than finishing with the tungsten
      carbide finishing bur. The Enhance PoGo polishing system produced smoother
      surfaces than the Sof-Lex disc polishing system; this difference was
      statistically highly significant (P < 0.0001). CONCLUSION: For both composites,
      the Mylar-formed surfaces were smoothest. Where indicated clinically, finishing
      is better conducted using a tungsten carbide bur- rather than a diamond finishing
      bur. The Enhance PoGo system was found to produce a smoother surface finish than
      the Sof-Lex system. CLINICAL SIGNIFICANCE: If finishing and polishing is required
      the use a tungsten carbide finishing bur followed by Enhance PoGo polishing may
      be found to result in the smoothest surface finish.

PMID- 29360493
TI  - Effects of a combined dietary, exercise and behavioral intervention and
      sympathetic system on body weight maintenance after intended weight loss: Results
      of a randomized controlled trial.
AB  - BACKGROUND: Lifestyle based weight loss interventions are hampered by long-term
      inefficacy. Prediction of individuals successfully reducing body weight would be
      highly desirable. Although sympathetic activity is known to contribute to energy
      homeostasis, its predictive role in body weight maintenance has not yet been
      addressed. OBJECTIVES: We investigated, whether weight regain could be modified
      by a weight maintenance intervention and analyzed the predictive role of weight
      loss-induced changes of the sympathetic system on long-term weight regain.
      DESIGN: 156 subjects (age > 18; BMI >= 27 kg/m2) participated in a 12-week weight
      reduction program. After weight loss (T0), 143 subjects (weight loss > 8%) were
      randomized to a 12-month lifestyle intervention or a control group. After 12
      months (T12) no further intervention was performed until month 18 (T18). Weight
      regain at T18 (regainBMI) was the primary outcome. Evaluation of systemic and
      tissue specific estimates of sympathetic system was a pre-defined secondary
      outcome. RESULTS: BMI was reduced by 4.67 +/- 1.47 kg/m2 during the initial
      weight loss period. BMI maintained low in subjects of the intervention group
      until T12 (+0.07 +/- 2.98 kg/m2; p = 0.58 compared to T0), while control subjects
      regained +0.98 +/- 1.93 kg/m2 (p < 0.001 compared to T0). The intervention group
      regained more weight than controls after ceasing the intervention (1.17 +/- 1.34
      vs. 0.57 +/- 0.93 kg/m2) until T18. Consequently, BMI was not different at T18
      (33.49 (32.64; 34.33) vs. 34.18 (33.61; 34.75) kg/m2; p=0.17). Weight loss
      induced modification of urinary metanephrine excretion independently predicted
      regainBMI (R2 = 0.138; p < 0.05). The lifestyle intervention did not modify the
      course of urinary metanephrines after initial weight loss. CONCLUSIONS: Our
      lifestyle intervention successfully maintained body weight during the
      intervention period. However, no long-term effect could be observed beyond the
      intervention period. Predictive sympathetic activity was not persistently
      modified by the intervention, which may partially explain the lack of long-term
      success of such interventions.

PMID- 29360494
TI  - New roles of reactive astrocytes in the brain; an organizer of cerebral ischemia.
AB  - The brain consists of neurons and much higher number of glial cells. They
      communicate each other, by which they control brain functions. The brain is
      highly vulnerable to several insults such as ischemia, but has a self-protective
      and self-repairing mechanisms against these. Ischemic tolerance or
      preconditioning is an endogenous neuroprotective phenomenon, where a mild non
      lethal ischemic episode can induce resistance to a subsequent severe ischemic
      injury in the brain. Because of its neuroprotective effects against cerebral
      ischemia or stroke, ischemic tolerance has been widely studied. However, almost
      all studies have been performed from the viewpoint of neurons. Glial cells are
      structurally in close association with synapses. Recent studies have uncovered
      the active roles of astrocytes in modulating synaptic connectivity, such as
      synapse formation, elimination and maturation, during development or pathology.
      However, glia-mediated ischemic tolerance and/or neuronal repairing have received
      only limited attention. We and others have demonstrated that glial cells,
      especially astrocytes, play a pivotal role in regulation of induction of ischemic
      tolerance as well as repairing/remodeling of neuronal networks by phagocytosis.
      Here, we review our current understanding of (1) glial-mediated ischemic
      tolerance and (2) glia-mediated repairing/remodeling of the penumbra neuronal
      networks, and highlight their mechanisms as well as their potential benefits,
      problems, and therapeutic application.

PMID- 29360495
TI  - MiR-143-3p inhibits the proliferation, cell migration and invasion of human
      breast cancer cells by modulating the expression of MAPK7.
AB  - Micro-RNAs have been reported to play crucial roles in a diversity of cellular
      processes such as cell proliferation, differentiation and development by
      regulating the expression of specific genes. They have also been shown to play
      vital roles in several diseases such as cancer. In the present study, we
      investigated the role of miR-143-3p in breast cancer. Our results showed that the
      expression of miR-143-3p is significantly downregulated in breast cancer cells.
      Upregulation of miR-143-3p inhibited the proliferation and migration of breast
      cancer cells. Conversely, inhibition of miR-143-3p promoted the proliferation of
      cancer cells. Bioinformatics analysis and other several experiments revealed
      MAPK7 as the potential target of miR-143-3p. Quantitative RT-PCR showed that the
      expression of MAPK7 correlated well with the expression of miR-143. Moreover, the
      inhibition of MAPK 7 in breast cancer cells abrogated the effects of miR-143
      indicating that miR-143-3p-exerted effects on breast cancer are mediated by
      MAPK7. Takentogether, these results provide strong clues about the therapeutic
      potential of miR-143-3p in the treatment of breast cancer.

PMID- 29360496
TI  - Is focal active colitis of greater clinical significance in pediatric patients? A
      retrospective review of 68 cases with clinical correlation.
AB  - Focal active colitis (FAC) is a histopathologic finding of uncertain clinical
      significance in individual patients. In adults, infection accounts for
      approximately 50%, Crohn's disease (CD) for 0-13%, and 20%-30% are idiopathic.
      One previous study of 29 cases of pediatric FAC showed a 28% rate of CD. This
      study reviewed a larger cohort of pediatric patients to determine what proportion
      had IBD, and whether an amount or pattern of inflammation could predict IBD.
      Sixty-eight patients aged <=18years with FAC were identified and reviewed.
      Patients with a prior diagnosis of IBD or chronic colitis in the index biopsies
      were excluded. Slides were assessed for a number of inflammatory criteria.
      Clinical data and final diagnoses were recorded. Data were analyzed using Pearson
      correlations and Fisher's exact chi2 analyses. Sixteen patients (24%) had a final
      diagnosis of IBD. When cases with terminal ileal (TI) inflammation were excluded,
      6 of 54 patients had a final diagnosis of IBD (11%). A final diagnosis of IBD was
      significantly associated with crypt abscesses and elevated serum inflammatory
      markers. IBD was significantly associated with TI inflammation. An amount or
      pattern of inflammation that could be used to predict IBD was not determined.
      This study demonstrated a 24% rate of IBD in pediatric patients with FAC;
      however, when patients with associated TI inflammation were excluded, the rate
      was 11%, similar to reported rates in adults. FAC in pediatric patients without
      terminal ileal inflammation does not appear to warrant more aggressive follow-up.

PMID- 29360497
TI  - Metabolomics-based mechanisms exploration of Huang-Lian Jie-Du decoction on
      cerebral ischemia via UPLC-Q-TOF/MS analysis on rat serum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian Jie-Du decoction (HLJDD), a
      traditional formula of Chinese medicine constituted with Rhizoma Coptidis,
      RadixScutellariae, CortexPhellodendri amurensis and Fructus Gardeniae, exhibits
      unambiguous therapeutic effect on cerebral ischemia via multi-targets action.
      Further investigation, however, is still required to explore the relationship
      between those mechanisms and targets through system approaches. MATERIALS AND
      METHODS: Rats of cerebral ischemia were completed by middle cerebral artery
      occlusion (MCAO) with reperfusion. Following evaluation of pharmacological
      actions of HLJDD on MCAO rats, the plasma samples from rats of control, MCAO and
      HLJDD-treated MCAO groups were prepared strictly and subjected to ultra
      performance liquid chromatography quadrupole time of flight mass spectrometry for
      metabolites analysis. The raw mass data were imported to MassLynx software for
      peak detection and alignment, and further introduced to EZinfo 2.0 software for
      orthogonal projection to latent structures analysis, principal component analysis
      and partial least-squares-discriminant analysis. The metabolic pathways assay of
      those potential biomarkers were performed with MetaboAnalyst through the online
      database, HMDB, Metlin, KEGG and SMPD. Those intriguing metabolic pathways were
      further investigated via biochemical assay. RESULTS: HLJDD ameliorated the MCAO
      induce cerebral damage and blocked the severe inflammation response. There were
      nineteen different biomarkers identified among control, MCAO and HLJDD-treated
      MCAO groups. Ten metabolic pathways were proposed from these significant
      metabolites. Incorporation with the biochemical assay of cerebral tissue,
      modulation of metabolic stress, regulation glutamate/GABA-glutamine cycle and
      enhancement of cholinergic neurons function were explored that involved in the
      actions of HLJDD on cerebral ischemia. CONCLUSION: HLJDD achieves therapeutic
      action on cerebral ischemia via coordinating the basic pathophysiological network
      of metabolic stress, glutamate metabolism, and acetylcholine levels and function.

PMID- 29360498
TI  - A pilot study on the characteristics of circulating T follicular helper cells in
      liver transplant recipients.
AB  - Circulating CD4+CXCR5+ T follicular helper cells (cTfh) have been demonstrated to
      be involved in B cell-mediated systemic autoimmune diseases and alloreactive
      responses following kidney transplantation; however, whether cTfh cells are
      involved in alloreactive responses after liver transplantation (LT) remains
      unclear. Our present study aimed to investigate the characteristics of cTfh, as
      well as CXCR3+CCR6-Tfh1, CXCR3-CCR6-Tfh2, and CXCR3-CCR6+Tfh17 subsets in liver
      allograft recipients. A total of 30 liver transplant recipients were enrolled in
      this study. The frequencies of cTfh, Tfh1, Tfh2, and Tfh17 subsets, and
      interleukin (IL)-21-producing Tfh cells in the circulating blood were analyzed by
      flow cytometry. The capacity of cTfh cells to help B cells differentiate into
      plasmablasts was determined one day before and one month after LT. The results
      revealed that the frequency of cTfh cells remained unaltered before and after LT.
      However, the frequency of the cTfh subsets (e.g., Tfh1 and Tfh2 cells) and B
      cells were reduced one month after LT. Functionally, the capacity of Tfh cells to
      produce IL-21 was reduced one month after LT. In addition, cTfh cells exhibited
      the capacity to help B cells differentiate into plasmablasts in an IL-21
      dependent manner in vitro, which was reduced after LT, despite the unaltered
      production of IgM and IgG by plasmablasts. Thus, our data suggest that cTfh cells
      may be involved in alloreactive responses following LT via helping B cells
      differentiate into plasmablasts and plasma cells.

PMID- 29360499
TI  - Bone marrow laminins influence hematopoietic stem and progenitor cell cycling and
      homing to the bone marrow.
AB  - Hematopoietic stem and progenitor cell (HSPC) functions are regulated by a
      specialized microenvironment in the bone marrow - the hematopoietic stem cell
      niche - of which the extracellular matrix (ECM) is an integral component. We
      describe here the localization of ECM molecules, in particular the laminin
      alpha4, alpha3 and alpha5 containing isoforms in the bone marrow. Laminin 421
      (composed of laminin alpha4, beta2, gamma1 chains) is identified as a major
      component of the bone marrow ECM, occurring abundantly surrounding venous sinuses
      and in a specialized reticular fiber network of the intersinusoidal spaces of
      murine bone marrow (BM) in close association with HSPC. Bone marrow from Lama4-/-
      mice is significantly less efficient in reconstituting the hematopoietic system
      of irradiated wildtype (WT) recipients in competitive bone marrow transplantation
      assays and shows reduced colony formation in vitro. This is partially due to
      retention of Lin-c-kit+Sca-1+CD48- long-term and short-term hematopoietic stem
      cells (LT-HSC/ST-HSC) in the G0 phase of the cell cycle in Lama4-/- bone marrow
      and hence a more quiescent phenotype. In addition, the extravasation of WT BM
      cells into Lama4-/- bone marrow is impaired, influencing the recirculation of
      HSPC. Our data suggest that these effects are mediated by a compensatory
      expression of laminin alpha5 containing isoforms (laminin 521/522) in Lama4-/-
      bone marrow. Collectively, these intrinsic and extrinsic effects lead to reduced
      HSPC numbers in Lama4-/- bone marrow and reduced hematopoietic potential.

PMID- 29360500
TI  - iDNA6mA-PseKNC: Identifying DNA N6-methyladenosine sites by incorporating
      nucleotide physicochemical properties into PseKNC.
AB  - N6-methyladenine (6mA) is one kind of post-replication modification (PTM or PTRM)
      occurring in a wide range of DNA sequences. Accurate identification of its sites
      will be very helpful for revealing the biological functions of 6mA, but it is
      time-consuming and expensive to determine them by experiments alone.
      Unfortunately, so far, no bioinformatics tool is available to do so. To fill in
      such an empty area, we have proposed a novel predictor called iDNA6mA-PseKNC that
      is established by incorporating nucleotide physicochemical properties into Pseudo
      K-tuple Nucleotide Composition (PseKNC). It has been observed via rigorous cross
      validations that the predictor's sensitivity (Sn), specificity (Sp), accuracy
      (Acc), and stability (MCC) are 93%, 100%, 96%, and 0.93, respectively. For the
      convenience of most experimental scientists, a user-friendly web server for
      iDNA6mA-PseKNC has been established at http://lin-group.cn/server/iDNA6mA-PseKNC,
      by which users can easily obtain their desired results without the need to go
      through the complicated mathematical equations involved.

PMID- 29360501
TI  - Emerging role of carbon monoxide in regulation of cellular pathways and in the
      maintenance of gastric mucosal integrity.
AB  - Heme oxygenase (HO) catalyzes the degradation of toxic free heme to the equimolar
      amounts of biliverdin, Fe2+ and concurrently releases of carbon monoxide (CO). CO
      is nowadays increasingly recognized as an important signaling molecule throughout
      the body that is involved in many physiological processes and shows
      multidirectional biological activity. Recent evidence indicates that CO exhibits
      the anti-inflammatory, anti-proliferative, anti-apoptotic, anti-aggregatory and
      vasodilatory properties. The cellular mechanisms underlying the activity of CO
      involve stimulation of cGMP-dependent signaling pathway and large conductance
      calcium activated K+ channels, the activation of mitogen-activated protein
      kinases and the nuclear factor k-light chain-enhancer of activated B cells
      transcription factor pathway. Stimulation of endogenous CO production by HO
      inducers or the inhalation of CO or the delivery of this gaseous molecule by
      novel pharmaceutical agents have been found in experimental animal models to be
      promising in the future therapy of various diseases. CO appears to act as a
      significant component of the complex mechanism of gastrointestinal (GI) mucosal
      defense. This gaseous molecule plays an important role in diabetic gastroparesis,
      prevention of the upper GI mucosal damage, post-operative ileus and the healing
      of ulcerative colitis. This review focuses on the better understanding mechanisms
      through which CO contributes to the mechanism of protection, resistance to injury
      and ulcer healing. It is becoming apparent that the pleiotropic effect of this
      molecule may increase clinical applicability of CO donors and their
      implementation in many pharmacological research areas, pharmaceutical industry
      and health-care system.

PMID- 29360502
TI  - Hypothalamic Akt-mediated signaling regulates food intake in chicks.
AB  - The central anorexigenic mechanism seems to be similar in mammals and chicks,
      because the appetite-suppressive action of a number of peptide hormones is
      similar in both species. Accumulating evidence in mammals has revealed that
      hypothalamic Akt-mediated signaling factors (for instance, mTOR and FOXO1) are
      significantly involved in the regulation of food intake. However, the role of
      hypothalamic Akt in feeding regulation is yet to be determined in chickens. In
      this study, we showed that pAkt (Thr308)/Akt, pFOXO1/FOXO1, and pS6 levels were
      significantly increased in the hypothalami of chicks refed 1 h after a 24 h-fast
      in correlation to increases in the plasma concentrations of insulin, one of the
      activators of the Akt-mediated signaling pathways. In addition, central
      administration of insulin increased the phosphorylation of Akt, FOXO1, and S6 in
      chicken hypothalami. Furthermore, intracerebroventricular injections of both
      phosphoinositide 3-kinase inhibitor LY294002 and mTOR inhibitor rapamyacin
      enhanced the food intake of chicks. These findings suggest that hypothalamic Akt
      mediated signaling pathways contribute to the regulation of food intake in
      chicks.

PMID- 29360503
TI  - Role of LncRNA MALAT-1 in hypoxia-induced PC12 cell injury via regulating p38MAPK
      signaling pathway.
AB  - OBJECTIVE: To investigate the role of LncRNA MALAT-1 in hypoxia-induced cell
      injury. METHODS: Pheochromocytoma-12 (PC12) cells were divided into seven groups:
      Control group, Hypoxia group (Cells treated with CoCl2), MALAT-1 group (Hypoxic
      cells treated with MALAT-1), NC group (Hypoxic cells treated with empty plasmid),
      MALAT-1 siRNA group (Hypoxic cells treated with siRNA MALAT-1), SB203580 group
      (Hypoxic cells treated with p38MAPK inhibitor), and MALAT-1 + SB20358 group. The
      content of reactive oxygen species (ROS), malondialdehyde (MDA), super oxide
      dismutase (SOD) and lactate dehydrogenase (LDH) was determined. Cell viability
      was detected by MTT assay. Apoptotic cells were observed by Hoechst 33258 and
      TUNEL staining assay. Mitochondrial membrane potential (MMP) was measured using
      JC1 vital dye. RESULTS: The decreased cell viability and increased expressions of
      MALAT-1 and p-p38 were observed in hypoxic PC12 cells time-dependently (P <
      0.05). Besides, hypoxic PC12 cells had an elevation in p-p38, ROS, MDA and LDH
      with the increased apoptotic cells, but a reduction in SOD and MMP, and these
      similar changes were more obvious in those hypoxic cells treated with MALAT-1
      when compared with Controls (all P < 0.05). However, the hypoxic PC12 cells
      treated with SB203580 and MALAT-1 siRNA led to opposite results compared with
      MALAT-1 group (all P < 0.05). Importantly, SB203580 could reverse the function of
      MALAT-1 in aggravating the hypoxia injury of PC12 cells. CONCLUSION: MALAT-1 can
      promote the apoptosis and oxidative stress of PC12 cells by activating p38MAPK
      pathway, thus aggravating the damage of PC12 cells induced by chemical hypoxia.

PMID- 29360504
TI  - New biomarkers for diagnosis and prognosis of localized prostate cancer.
AB  - The diagnostics and management of localized prostate cancer is complicated
      because of cancer heterogeneity and differentiated progression in various
      subgroups of patients. As a prostate cancer biomarker, FDA-approved detection
      assay for serum prostate specific antigen (PSA) and its derivatives are not
      potent enough to diagnose prostate cancer, especially high-grade disease (Gleason
      >=7). To date, a collection of new biomarkers was developed. Some of these
      markers are superior for primary screening while others are particularly helpful
      for cancer risk stratification, detection of high-grade cancer, and prediction of
      adverse events. Two of those markers such as proPSA (a part of the Prostate
      Health Index (PHI)) and prostate specific antigen 3 (PCA3) (a part of the PCA3
      Progensa test) were recently approved by FDA for clinical use. Other markers are
      not PDA-approved yet but are available from Clinical Laboratory Improvement
      Amendment (CLIA)-certified clinical laboratories. In this review, we characterize
      diagnostic performance of these markers and their diagnostic and prognostic
      utility for prostate cancer.

PMID- 29360505
TI  - Biogas upgrading and utilization: Current status and perspectives.
AB  - Biogas production is an established sustainable process for simultaneous
      generation of renewable energy and treatment of organic wastes. The increasing
      interest of utilizing biogas as substitute to natural gas or its exploitation as
      transport fuel opened new avenues in the development of biogas upgrading
      techniques. The present work is a critical review that summarizes state-of-the
      art technologies for biogas upgrading and enhancement with particular attention
      to the emerging biological methanation processes. The review includes
      comprehensive description of the main principles of various biogas upgrading
      methodologies, scientific and technical outcomes related to their biomethanation
      efficiency, challenges that have to be addressed for further development and
      incentives and feasibility of the upgrading concepts.

PMID- 29360506
TI  - Chromosomal mutations that accompany qnr in clinical isolates of Escherichia
      coli.
AB  - We examined 13 qnr-positive and 14 qnr-negative clinical isolates of Escherichia
      coli for mutations previously seen in a qnr-containing laboratory strain exposed
      to supra minimum inhibitory concentrations (MICs) of ciprofloxacin. Among the qnr
      positive strains, those with ciprofloxacin MICs of >= 2 ug/mL had at least one
      mutation in gyrA. Mutations in parC were present in strains with a ciprofloxacin
      MIC of >= 128 ug/mL. The 6 most ciprofloxacin-resistant strains contained
      additional plasmid-mediated quinolone resistance determinants. aac(6')-Ib-cr was
      found in 5 of the 6 strains. Eleven of the 13 strains had alterations in MarR, 9
      in SoxR, and 5 had mutations in AcrR. All had elevated expression of at least one
      efflux pump gene, predominantly acrA (92% of the strains), followed by mdtE (54%)
      and ydhE (46%). Nine had functionally silent alterations in rfa, two had
      mutations in gmhB, and one of these also had a mutation in surA. An E. coli with
      ciprofloxacin MIC of 1024 ug/mL contained 4 different plasmid-mediated quinolone
      resistance determinants as well as gyrA, parC, parE and pump overexpression
      mutations. Nine of the 14 qnr-negative strains had mutations in topoisomerase
      genes with a ciprofloxacin MIC of 0.25 to 256 ug/mL. The three most resistant
      strains also had mutations in parE. Twelve had alterations in MarR, 10 in SoxR
      and 5 in AcrR. Ten of the 14 strains had elevated expression of efflux pumps with
      acrA (71.4%), followed by ydhE (50%) and mdtE (14.3%). A diversity of resistance
      mechanisms occurs in clinical isolates with and without qnr genes.

PMID- 29360508
TI  - Uncommon Cause of Abdominal Pain, Nausea, and Vomiting.

PMID- 29360509
TI  - Subcapsular Hepatic Hematoma Resulting From Hepatic Microaneurysms in a Patient
      With Systemic Amyloidosis.

PMID- 29360507
TI  - Influence of breast cancer resistance protein and P-glycoprotein on tissue
      distribution and excretion of Ko143 assessed with PET imaging in mice.
AB  - Ko143 is a reference inhibitor of the adenosine triphosphate-binding cassette
      (ABC) transporter breast cancer resistance protein (humans: ABCG2, rodents:
      Abcg2) for in vitro and in vivo use. Previous in vitro data indicate that Ko143
      binds specifically to ABCG2/Abcg2, suggesting a potential utility of Ko143 as a
      positron emission tomography (PET) tracer to assess the density (abundance) of
      ABCG2 in different tissues. In this work we radiolabeled Ko143 with carbon-11
      (11C) and performed small-animal PET experiments with [11C]Ko143 in wild-type,
      Abcg2(-/-), Abcb1a/b(-/-) and Abcb1a/b(-/-)Abcg2(-/-) mice to assess the
      influence of Abcg2 and Abcb1a/b on tissue distribution and excretion of
      [11C]Ko143. [11C]Ko143 was extensively metabolized in vivo and unidentified
      radiolabeled metabolites were found in all investigated tissues. We detected no
      significant differences between wild-type and Abcg2(-/-) mice in the distribution
      of [11C]Ko143-derived radioactivity to Abcg2-expressing organs (brain, liver and
      kidney). [11C]Ko143 and possibly its radiolabeled metabolites were transported by
      Abcb1a and not by Abcg2 at the mouse blood-brain barrier. [11C]Ko143-derived
      radioactivity underwent both hepatobiliary and urinary excretion, with Abcg2
      playing a possible role in mediating the transport of radiolabeled metabolites of
      [11C]Ko143 from the kidney into urine. Experiments in which a pharmacologic dose
      of unlabeled Ko143 (10 mg/kg) was co-administered with [11C]Ko143 revealed
      pronounced effects of the vehicle used for Ko143 formulation (containing
      polyethylene glycol 300 and polysorbate 80) on radioactivity distribution to the
      brain and the liver, as well as on hepatobiliary and urinary excretion of
      radioactivity. Our results highlight the challenges associated with the
      development of PET tracers for ABC transporters and emphasize that inhibitory
      effects of pharmaceutical excipients on membrane transporters need to be
      considered when performing in vivo drug-drug interaction studies. Finally, our
      study illustrates the power of small-animal PET to assess the interaction of drug
      molecules with membrane transporters on a whole body level.

PMID- 29360510
TI  - An Uncommon Portal Vein Abnormality.

PMID- 29360511
TI  - Responders and non-responders to influenza vaccination: A DNA methylation
      approach on blood cells.
AB  - Several evidences indicate that aging negatively affects the effectiveness of
      influenza vaccination. Although it is well established that immunosenescence has
      an important role in vaccination response, the molecular pathways underlying this
      process are largely unknown. Given the importance of epigenetic remodeling in
      aging, here we analyzed the relationship between responsiveness to influenza
      vaccination and DNA methylation profiles in healthy subjects of different ages.
      Peripheral blood mononuclear cells were collected from 44 subjects (age range: 19
      90 years old) immediately before influenza vaccination. Subjects were
      subsequently classified as responders or non-responders according to
      hemagglutination inhibition assay 4-6 weeks after the vaccination. Baseline whole
      genome DNA methylation in peripheral blood mononuclear cells was analyzed using
      the Illumina(r) Infinium 450 k microarray. Differential methylation analysis
      between the two groups (responders and non-responders) was performed through an
      analysis of variance, correcting for age, sex and batch. We identified 83 CpG
      sites having a nominal p-value <.001 and absolute difference in DNA methylation
      of at least 0.05 between the two groups. For some CpG sites, we observed age
      dependent decrease or increase in methylation, which in some cases was specific
      for the responders and non-responders groups. Finally, we divided the cohort in
      two subgroups including younger (age < 50) and older (age >= 50) subjects and
      compared DNA methylation between responders and non-responders, correcting for
      sex and batch in each subgroup. We identified 142 differentially methylated CpG
      sites in the young subgroup and 305 in the old subgroup, suggesting a larger
      epigenetic remodeling at older ages. Interestingly, some of the differentially
      methylated probes mapped in genes involved in immunosenescence (CD40) and in
      innate immunity responses (CXCL16, ULK1, BCL11B, BTC). In conclusion, the
      analysis of epigenetic landscape can shed light on the biological basis of
      vaccine responsiveness during aging, possibly providing new appropriate
      biomarkers of this process.

PMID- 29360513
TI  - Electro-olfactogram Responses Before and After Aversive Olfactory Conditioning in
      Humans.
AB  - The aim of the present study was to investigate whether repetitive aversive odor
      conditioning induced changes at the level of the peripheral olfactory system in
      humans. A total of 51 volunteers participated. A pair of indistinguishable odor
      enantiomers [(+)-rose oxide and (-)-rose oxide] were used as stimuli. During the
      pre-conditioning, participants' ability to discriminate between the two odors was
      assessed using a three-alternative, forced-choice discrimination test. In
      addition, electro-olfactograms (EOG) from the olfactory epithelium were recorded.
      Participants underwent three conditioning sessions on consecutive days. The
      experimental group received an electrical stimulus to the forearm only following
      (+)-rose oxide presentation, whereas its enantiomer sibling was never paired with
      the aversive stimulus; the control group did not receive any electrical
      stimulation. During the post-conditioning session, their ability to discriminate
      the two enantiomers was assessed again using the discrimination test and EOG
      recordings were obtained similarly to the pre-conditioning session. Results
      showed significant differences in the peripheral electrophysiological responses
      between the conditioned and the unconditioned stimulus, demonstrating
      contextually induced changes at the level of the first neuron in the olfactory
      system.

PMID- 29360512
TI  - Histologic Lung Cancer Incidence Rates and Trends Vary by Race/Ethnicity and
      Residential County.
AB  - INTRODUCTION: Lung cancer incidence is higher among non-Hispanic (NH) blacks than
      among the NH white and Hispanic populations in the United States. However,
      national cancer estimates may not always reflect the cancer burden in terms of
      disparities and incidence in small geographic areas, especially urban-rural
      disparities. Moreover, there is a gap in the literature regarding rural-urban
      disparities in terms of cancer histologic type. METHODS: Using population-based
      cancer registry data-Surveillance, Epidemiology and End Results and National
      Program of Cancer Registries data-we present age-adjusted histologic rates and
      trends by race/ethnicity and residential county location at the time of first
      cancer diagnosis. Rate ratios were calculated to examine racial/ethnic
      differences in rates. Annual percent change was calculated to measure changes in
      rates over time. RESULTS: We found that declines in squamous cell carcinoma are
      occurring fastest in metropolitan counties, whereas rates of adenocarcinoma
      increased fastest in counties nonadjacent to metropolitan areas. Further,
      although NH black men have increased lung cancer incidence compared with NH white
      and Hispanic men in all geographic locations, we found that the degree of the
      disparity increases with increasing rurality of residence. Finally, we discovered
      that among women whose lung cancer was diagnosed when they were younger than 55
      years, the incidence of squamous cell carcinoma and adenocarcinoma was higher for
      NH blacks than for NH whites. CONCLUSIONS: Our results highlight disparities
      among NH blacks in nonadjacent rural areas. These findings may have significant
      impact for the implementation of smoking cessation and lung cancer screening
      programs.

PMID- 29360514
TI  - Robotic, Laparoscopic, or Open Hysterectomy: Surgical Outcomes by Approach in
      Endometrial Cancer.
AB  - STUDY OBJECTIVES: To compare patient outcomes by surgical approach in the
      management of endometrial cancer (EC) in Washington State from 2008 to 2013.
      DESIGN: Population-based retrospective cohort study (Canadian Task Force
      classification II-2). SETTING: Washington State. PATIENTS: EC patients treated
      with robotic-assisted surgery (RAS), laparoscopy (LS), or laparotomy (XLAP).
      INTERVENTIONS: Comprehensive Hospital Abstract Reporting System to identify
      patients and assess the association of surgical approach with length of stay,
      readmissions, and perioperative complications. MEASUREMENTS AND RESULTS: We
      identified 3712 cases of EC managed with either RAS, LS, or XLAP. Mean length of
      stay was not clinically different for RAS (1.5 days) and LS (1.6 days) but was
      2.31 days longer for XLAP compared with LS (p < .001). Odds of any readmission
      did not differ for either RAS or XLAP compared with LS; however, early
      readmissions were half as likely for RAS compared with LS (p = .014).
      Complications were more than 2.5 times as likely for XLAP versus LS (p < .001),
      whereas complications did not differ for RAS versus LS (p = .931). CONCLUSIONS:
      RAS is as an alternative to LS in the treatment of EC and is preferable to XLAP.
      The use of RAS resulted in fewer early readmissions compared with LS and resulted
      in an increased proportion of cases via minimally invasive surgery.

PMID- 29360515
TI  - Choosing Wisely BMT: American Society for Blood and Marrow Transplantation and
      Canadian Blood and Marrow Transplant Group's List of 5 Tests and Treatments to
      Question in Blood and Marrow Transplantation.
AB  - Choosing Wisely encourages dialogue about reducing unnecessary procedures, tests,
      or treatments in healthcare. The American Society for Blood and Marrow
      Transplantation (ASBMT) and Canadian Blood and Marrow Transplant Group (CBMTG)
      established a Choosing Wisely BMT Task Force whose objective was to create a list
      of top 5 practices in blood and marrow transplantation to be questioned. The Task
      Force consisted of representatives from ASBMT's Quality Outcomes, Education, and
      Practice Guidelines committees; ASBMT's Pharmacy Special Interest Group; CBMTG
      Program Directors; and Center for International Blood and Marrow Transplant
      Research (CIBMTR). Suggestions for current transplantation practices to question
      were elicited from the CBMTG Program Directors; members of ASBMT's Quality
      Outcomes, Practice Guidelines, and Education committees; and chairs of the CIBMTR
      scientific working committees. We received 119 unique suggestions that were
      ranked based on their potential impact on harm reduction, cost reduction,
      necessity of the test or practice, and the strength of available evidence.
      Through a modified Delphi process, suggestions were narrowed down to 6, which
      were then subjected to systematic reviews. The final 5 recommendations focus on
      graft source for patients with aplastic anemia, corticosteroid dose for initial
      treatment of graft-versus-host-disease, optimal number of umbilical cord blood
      units for transplantation, graft source in matched unrelated donor
      transplantation, and use of prophylactic intravenous immunoglobulin in transplant
      recipients. These Choosing Wisely BMT recommendations are relevant to the current
      clinical practice of blood and marrow transplantation and focus on tests,
      treatments, or procedures that may be harmful, wasteful, or for which there is no
      apparent clinical benefit.

PMID- 29360516
TI  - Bilingualism and healthy aging: Aging effects and neural maintenance.
AB  - Speaking more than one language is associated with neurocognitive benefits in
      seniors (Alladi et al. 2013). Few studies however have tested this hypothesis
      directly by comparing bilingual seniors who vary in chronological age. We report
      a Voxel-Based Morphometry (VBM) study showing cumulative effects of age on grey
      matter volume (GMV) in brain structures that are involved in cognitive control in
      bilingual seniors and found no differences in RT or accuracy between bilingual
      and monolingual seniors on a behavioral test of cognitive control called the
      Attentional Network Task (ANT), and no differences in GMV for selected ROIs
      between groups. However, chronological age predicted the size of interference and
      conflict effects for monolingual speakers only. We also observed a more
      widespread pattern of bilateral aging-effcts in brain regions that are
      classically associated with aging in monolingual speakers compared to bilingual
      speakers. Notably, GMV in the dorsal anterior cingulate cortex (dACC) and the
      level of daily exposure to a second language (L2) independently predict
      performance on the ANT in bilingual speakers. We conclude that regular (daily)
      bilingual experience mitigates the typical effects of aging on cognitive control
      at the behavioral and the neural level.

PMID- 29360517
TI  - The spatial distribution of perseverations in neglect patients during a nonverbal
      fluency task depends on the integrity of the right putamen.
AB  - Deficient inhibitory control leading to perseverative behaviour is often observed
      in neglect patients. Previous studies investigating the relationship between
      response inhibition and visual attention have reported contradictory results:
      some studies found a linear relationship between neglect severity and
      perseverative behaviour whereas others could not replicate this result. The aim
      of the present study was to shed further light on the interplay between visual
      attention and response inhibition in neglect, and to investigate the neural
      underpinnings of this interplay. We propose the use of the Five-Point Test, a
      test commonly used to asses nonverbal fluency, as a novel approach in the context
      of neglect. In the Five-Point Test, participants are required to generate as many
      different designs as possible, by connecting dots within forty rectangles. We
      hypothesised that, because of its clear definition of perseverative errors, the
      Five-Point Test would accurately assess both visual attention as well as
      perseverative behaviour. We assessed 46 neglect patients with right-hemispheric
      stroke, and performed voxel-based lesion-symptom mapping (VLSM) to identify
      neural substrates of perseverative behaviour as well as the spatial distribution
      of perseverations. Our results showed that the Five-Point Test can reliably
      measure neglect and perseverative behaviour. We did not find any significant
      relationship between neglect severity and the frequency of perseverations.
      However, within the subgroup of neglect patients who displayed perseverative
      behaviour, the spatial distribution of perseverations significantly depended on
      the integrity of the right putamen. We discuss the putative role of the putamen
      as a potential subcortical hub to modulate the complex integration between visual
      attention and response inhibition processes.

PMID- 29360518
TI  - Neuropsychological evidence for the crucial role of the right arcuate fasciculus
      in the face-based mentalizing network: A disconnection analysis.
AB  - Recent evidence from axonal stimulation mapping studies suggests that at least
      two white matter connectivities in the right hemisphere may be involved in face
      based mentalizing, i.e. the ability to infer complex cognitive and affective
      states from human faces: the inferior fronto-occipital (IFOF) and the superior
      longitudinal/arcuate (SLF/AF) fasciculi. However, to date, only a handful of
      neuropsychological studies have focused on the white matter tracts subserving
      mentalizing in general, and face-based mentalizing in particular. Therefore, the
      main goal of this study was to confirm the abovementioned results by applying
      voxelwise and tractwise lesion-symptom analyses to a set of behavioral data
      obtained from a large and homogeneous group of neurological participants. More
      precisely, 122 patients operated on for diffuse low-grade glioma were assessed
      postoperatively with the well-validated "Reading the Mind in the Eyes" (RME)
      test. For each patient, the resection cavity and the residual tumor infiltration
      were mapped separately on the respective postoperative structural MRI. Behavioral
      data, previously controlled for sociodemographic factors, were then submitted to
      a standard voxel-based and to a less conservative, region-of-interest (ROI)
      based, lesion-deficit analyses. Results were invariably the same: no anatomo
      functional relationships were pinpointed by these investigations, making thus
      impossible the cortical topological localization of mentalizing deficits. In a
      second time, two kinds of tractwise lesion-symptom analyses based on the damaged
      volume and the disconnection probabilities of the white matter tracts, were
      performed. All results were corrected with the Bonferroni correction. Converging
      and strong evidence was found that resection-related disconnection of the right
      AF is especially deleterious for face-based mentalizing. More anecdotally, we
      identified the involvement of certain ventral tracts, especially the IFOF and the
      uncinate fasciculus (UF). Taken as a whole, the reported findings confirm the
      critical role of the right AF in mentalizing abilities. From a more clinical
      standpoint, they highlight the necessity to perform an intraoperative map of this
      connectivity during awake surgery in order to avoid long-lasting social cognition
      disorders.

PMID- 29360519
TI  - Language and alexithymia: Evidence for the role of the inferior frontal gyrus in
      acquired alexithymia.
AB  - The clinical relevance of alexithymia, a condition associated with difficulties
      identifying and describing one's own emotion, is becoming ever more apparent.
      Increased rates of alexithymia are observed in multiple psychiatric conditions,
      and also in neurological conditions resulting from both organic and traumatic
      brain injury. The presence of alexithymia in these conditions predicts poorer
      regulation of one's emotions, decreased treatment response, and increased burden
      on carers. While clinically important, the aetiology of alexithymia is still a
      matter of debate, with several authors arguing for multiple 'routes' to impaired
      understanding of one's own emotions, which may or may not result in distinct
      subtypes of alexithymia. While previous studies support the role of impaired
      interoception (perceiving bodily states) in the development of alexithymia, the
      current study assessed whether acquired language impairment following traumatic
      brain injury, and damage to language regions, may also be associated with an
      increased risk of alexithymia. Within a sample of 129 participants with
      penetrating brain injury and 33 healthy controls, neuropsychological testing
      revealed that deficits in a non-emotional language task, object naming, were
      associated with alexithymia, specifically with difficulty identifying one's own
      emotions. Both region-of-interest and whole-brain lesion analyses revealed that
      damage to language regions in the inferior frontal gyrus was associated with the
      presence of both this language impairment and alexithymia. These results are
      consistent with a framework for acquired alexithymia that incorporates both
      interoceptive and language processes, and support the idea that brain injury may
      result in alexithymia via impairment in any one of a number of more basic
      processes.

PMID- 29360520
TI  - Effectiveness of combination therapy versus monotherapy with a third-generation
      cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis.
AB  - OBJECTIVE: Combining a macrolide or a fluoroquinolone to beta-lactam regimens in
      the treatment of patients with moderate to severe community-acquired pneumonia is
      recommended by the international guidelines. However, the information in patients
      with bacteraemic pneumococcal pneumonia is limited. METHODS: A propensity score
      technique was used to analyze prospectively collected data from all patients with
      bacteraemic pneumococcal pneumonia admitted from 2000 to 2015 in our institution,
      who had received empirical treatment with third-generation cephalosporin in
      monotherapy or plus macrolide or fluoroquinolone. RESULTS: We included 69
      patients in the monotherapy group and 314 in the combination group. After
      adjustment by PS for receiving monotherapy, 30-day mortality (OR 2.89; 95% CI
      1.07-7.84) was significantly higher in monotherapy group. A higher 30-day
      mortality was observed in monotherapy group in both 1:1 and 1:2 matched samples
      although it was statistically significant only in 1:2 sample (OR: 3.50 (95% CI
      1.03-11.96), P = 0.046). CONCLUSIONS: Our study suggests that in bacteraemic
      pneumococcal pneumonia, empirical therapy with a third-generation cephalosporin
      plus a macrolide or a fluoroquinolone is associated with a lower mortality rate
      than beta-lactams in monotherapy. These results support the recommendation of
      combination therapy in patients requiring admission with moderate to severe
      disease.

PMID- 29360521
TI  - Unexpected increase in invasive maternal Group B Streptococcus bacteraemia in a
      maternity hospital in Dublin, Ireland (May to September 2017) associated with
      subtle signs of sepsis and unreliable sepsis biomarkers.

PMID- 29360522
TI  - On Earth, there would be a number of fundamental kinds of primary cells -
      cellular domains - greater than or equal to four.
AB  - In the studies regarding the deep nodes of the tree of life, there is an
      assumption that might be false. Usually, it is assumed that these nodes - that is
      to say, those for example regarding the ancestors of bacteria and archaea - are
      believed to be completely evolved cells and not protocells. In other words, in
      these studies, it is rarely stressed that, on the contrary, these nodes might
      correspond to evolutionary stages of premature cells, namely, progenotes. This
      observation has extremely relevant consequences. Indeed, if the nodes, for
      example, of the ancestors of bacteria and archaea would correspond to progenotic
      evolutionary stages, then this should imply that the number of fundamental kinds
      of primary cells (cellular domains), present on Earth, would be at least four and
      not two or three as it is currently believed. As a matter of fact, if these two
      nodes would correspond to two progenotes then, evidently, the fully evolved cells
      (genotes) - to which we should refer to be able to establish how many fundamental
      kinds of primary cells are present on Earth - would characterize less deep nodes
      of these two. Thus, since there is a strong evidence that the ancestors of
      archaea and bacteria have been of progenotes, these reasonings would assume a
      particular importance. For instance, it is maintained that one of these
      fundamental primary cells might be represented by the typical cell of superphylum
      of the DPANN. In other words, the DPANN superphylum might be a so far non
      recognized cellular domain of life.

PMID- 29360523
TI  - Thiamine and Cardiovascular Disease: A Literature Review.
AB  - Thiamine is a water-soluble vitamin that plays an important role in the energy
      metabolism in the human body. Deficiency in thiamine can lead to neurological
      abnormalities and congestive heart failure (HF), known as dry beriberi and wet
      beriberi respectively. Several populations are at higher risk for thiamine
      deficiency, most notably persons with chronic alcoholism. This article aims to
      provide a review of current literature on the role of thiamine in the human body,
      the current scope of thiamine deficiency, and explore the specific effects of
      thiamine deficiency and supplementation on the cardiovascular system. HF as a
      result of thiamine deficiency can have non-specific presentations, often leading
      to delayed diagnosis and treatment. Having an understanding of pathophysiology of
      thiamine deficiency and considering thiamine deficiency as one of the
      differentials in patients with new onset HF of unknown etiology with the
      appropriate risk factors is important in clinical practice.

PMID- 29360524
TI  - Dual (Anticoagulant Plus Single Antiplatelet) vs Triple (Anticoagulant Plus Dual
      Antiplatelet) Antithrombotic Therapy - "Real World" Experience.
AB  - Atrial fibrillation (AF) is a common arrhythmia that increases in prevalence with
      advancing age and in patients with coronary artery disease, revascularization,
      particularly with percutaneous coronary intervention (PCI), is also common. Both
      disease states have thrombosis as a core pathophysiologic process which requires
      treatment - low sheer stress thrombi in AF and intracoronary high sheer stress
      thrombi in PCI. For the 10-20% of patients who have both AF and undergo PCI,
      preventing thrombotic complications will require inhibition of both processes
      requiring simultaneous use of anticoagulation and antiplatelet therapy. There is
      a broad experience of combining oral anticoagulation therapy, used to prevent
      stroke and systemic embolization, in AF with dual antiplatelet therapy, used to
      prevent stent thrombosis and thrombotic coronary events. This "triple
      antithrombotic therapy" (TT) has been evaluated through many observation studies,
      both small and large. TT has more frequently been associated with a significant
      increase in bleeding events with non-significant reduction in thrombotic events.
      Current guidelines recommend shorter duration of TT, especially in patients with
      high risk of bleeding.

PMID- 29360526
TI  - Short-term ibrutinib therapy suppresses skin test responses and eliminates IgE
      mediated basophil activation in adults with peanut or tree nut allergy.

PMID- 29360525
TI  - Health risks and precautions for visitors to the Tokyo 2020 Olympic and
      Paralympic Games.
AB  - BACKGROUND: In 2020, Japan will host the Tokyo Olympic and Paralympic Games in
      2020 (Tokyo 2020) which will involve a large population influx from various
      countries to Tokyo, the most populated city in Japan. We summarize the potential
      health risks for visitors to Tokyo 2020, related to communicable disease risks
      and other health threats, based on recent national and local surveillance
      reports. METHODS: We reviewed up-to-date surveillance reports published by the
      National Institute of Infectious Diseases and Tokyo Metropolitan Infectious
      Disease Surveillance Center. RESULTS: Communicable disease risks for vaccine
      preventable illnesses such as measles and rubella, as well as food and waterborne
      diseases represent the most likely risks. The risk of acquiring vector-borne
      diseases is considered low in Japan. On the other hand, however, heat-related
      illness represents a potential risk, as Tokyo 2020 is scheduled during the
      hottest season in Japan, with temperatures generally expected to exceed 30 
      degrees C. CONCLUSION: Maintaining an up-to-date routine vaccination schedule is
      highly recommended for visitors attending the Tokyo 2020 and appropriate hygiene
      measures for food and waterborne diseases as well as health promotion for heat
      related illness. It may also be useful to increase the number of multilingual
      triage clinicians whom can be placed within emergency departments during the
      Tokyo 2020 to provide first contact services and coordination of emergency care
      among non-Japanese speaking visitors to Tokyo.

PMID- 29360527
TI  - Engineering and stable production of recombinant IgE for cancer immunotherapy and
      AllergoOncology.

PMID- 29360528
TI  - Intravenous immunoglobulin treatment abrogates transplacental autoantibody
      transfer in a murine pemphigus model.

PMID- 29360529
TI  - WATER: A Double-Blind, Randomized, Controlled Trial of Aquablation(r) vs
      Transurethral Resection of the Prostate in Benign Prostatic Hyperplasia.
AB  - PURPOSE: We compared the safety and efficacy of Aquablation and transurethral
      prostate resection for the treatment of lower urinary tract symptoms related to
      benign prostatic hyperplasia. MATERIALS AND METHODS: In a double-blind,
      multicenter, prospective, randomized, controlled trial 181 patients with moderate
      to severe lower urinary tract symptoms related to benign prostatic hyperplasia
      underwent transurethral prostate resection or Aquablation. The primary efficacy
      end point was the reduction in International Prostate Symptom Score at 6 months.
      The primary safety end point was the development of Clavien-Dindo persistent
      grade 1, or 2 or higher operative complications. RESULTS: Mean total operative
      time was similar for Aquablation and transurethral prostate resection (33 vs 36
      minutes, p = 0.2752) but resection time was lower for Aquablation (4 vs 27
      minutes, p <0.0001). At month 6 patients treated with Aquablation and
      transurethral prostate resection experienced large I-PSS improvements. The
      prespecified study noninferiority hypothesis was satisfied (p <0.0001). Of the
      patients who underwent Aquablation and transurethral prostate resection 26% and
      42%, respectively, experienced a primary safety end point, which met the study
      primary noninferiority safety hypothesis and subsequently demonstrated
      superiority (p = 0.0149). Among sexually active men the rate of anejaculation was
      lower in those treated with Aquablation (10% vs 36%, p = 0.0003). CONCLUSIONS:
      Surgical prostate resection using Aquablation showed noninferior symptom relief
      compared to transurethral prostate resection but with a lower risk of sexual
      dysfunction. Larger prostates (50 to 80 ml) demonstrated a more pronounced
      superior safety and efficacy benefit. Longer term followup would help assess the
      clinical value of Aquablation.

PMID- 29360530
TI  - Perinephric Hematoma Size is Independently Associated with the Need for
      Urological Intervention in Multisystem Blunt Renal Trauma.
AB  - PURPOSE: We examined radiographic predictors of intervention for blunt renal
      trauma independent of AAST-OIS (American Association for the Surgery of Trauma
      Organ Injury Scale). MATERIALS AND METHODS: A total of 328 patients with blunt
      renal trauma from October 2004 to December 2014 were identified for analysis.
      Hospital records and diagnostic imaging were reviewed to identify the need for
      urological intervention, including angiographic embolization, nephrectomy,
      renorrhaphy, ureteral stenting or percutaneous drainage. Factors examined
      included patient age, gender, length of stay, ISS (Injury Severity Score), AAST
      OIS, laceration location, length and number, perinephric hematoma
      characteristics, intravascular contrast extravasation and devitalized segment
      status. Descriptive statistics and binary logistic regression were performed as
      appropriate. RESULTS: Mean patient age was 37.0 years and mean ISS was 31.7. A
      total of 31 urological interventions were required in 27 patients (8.2%),
      including ureteral stenting in 38.7%, angiographic embolization in 32.3%,
      nephrectomy in 22.6%, renorrhaphy in 3.2% and percutaneous drainage in 3.2%. On
      univariate analysis AAST-OIS, hematoma diameter, hematoma area, intravascular
      contrast extravasation, laceration length, laceration number, degree of
      devitalization and devitalized fragment presence were associated with the need
      for intervention (each p <0.001). On multivariate analysis only AAST-OIS grade
      (OR 69.4, 95% CI 6.4-748.3, p <0.001) and hematoma diameter (OR 1.5, 95% CI 1.1
      1.9, p = 0.004) or area (OR 1.03, 95% CI 1.01-1.06, p = 0.012) remained
      associated with urological intervention. CONCLUSIONS: Although AAST-OIS is
      strongly associated with the need for urological intervention, perinephric
      hematoma size is also independently associated with this occurrence. Perinephric
      hematoma diameter should be considered during clinical decision making and
      incorporated into a revised injury grading system.

PMID- 29360531
TI  - Minocycline diminishes the rotenone induced neurotoxicity and glial activation
      via suppression of apoptosis, nitrite levels and oxidative stress.
AB  - The study was conducted to evaluate the effect of minocycline against pesticide
      rotenone induced adverse effects in different rat brain regions. Assessment of
      oxidative stress, nitrite levels, degenerating neurons and level of cleaved
      caspase-3 was done in frontal cortex, mid brain, hippocampus and striatum regions
      of rat brain. In addition the expression profile of neuronal (MAP2), astrocytes
      (GFAP) and microglia (cd11b) markers was done after treatments. Rotenone induced
      DNA fragmentation was also assessed in all studied rat brain regions by utilizing
      comet assay. Rotenone administration caused significantly decreased level of
      glutathione along with increased level of nitrite and lipid peroxidation.
      Significant oxidative and nitrosative stress was also observed after rotenone
      administration which was considerably inhibited in minocycline treated rats in
      time dependent manner. Fluorojade staining and levels of cleaved caspase 3 showed
      the degeneration of neurons and apoptosis respectively in studied rat brain
      regions which were further inhibited with minocycline treatment. Rotenone
      administration caused significantly increased reactivity of astrocytes, microglia
      and altered neuronal morphology in rat brain regions which was also partially
      restored with minocycline treatment. In conclusion, present study showed that
      minocycline treatment attenuated the rotenone induced oxidative stress, nitrite
      level, degeneration of neurons, augmented glial reactivity and apoptosis.

PMID- 29360533
TI  - Zoanthid mucus as new source of useful biologically active proteins.
AB  - Palythoa caribaeorum is a very common colonial zoanthid in the coastal reefs of
      Brazil. It is known for its massive production of mucus, which is traditionally
      used in folk medicine by fishermen in northeastern Brazil. This study identified
      biologically active compounds in P. caribaerum mucus. Crude mucus was collected
      during low tides by the manual scraping of colonies; samples were maintained in
      an ice bath, homogenized, and centrifuged at 16,000 g for 1 h at 4  degrees C;
      the supernatant (mucus) was kept at -80  degrees C until use. The enzymatic
      (proteolytic and phospholipase A2), inhibitory (metallo, cysteine and serine
      proteases), and hemagglutinating (human erythrocyte) activities were determined.
      The results showed high levels of cysteine and metallo proteases, intermediate
      levels of phosholipase A2, low levels of trypsin, and no elastase and
      chymotrypsin like activities. The mucus showed potent inhibitory activity on
      snake venom metalloproteases and cysteine proteinase papain. In addition, it
      showed agglutinating activity towards O+, B+, and A+ erythrocyte types. The
      hemostatic results showed that the mucus prolongs the aPTT and PT, and strongly
      inhibited platelet aggregation induced by arachidonic acid, collagen,
      epinephrine, ADP, and thrombin. The antimicrobial activity was tested on 15
      strains of bacteria and fungi through the radial diffusion assay in agar, and no
      activity was observed. Compounds in P. caribaeorum mucus were analyzed for the
      first time in this study, and our results show potential pharmacological
      activities in these compounds, which are relevant for use in physiopathological
      investigations. However, the demonstration of these activities indicates caution
      in the use of crude mucus in folk medicine. Furthermore, the present or absent
      activities identified in this mucus suggest that the studied P. caribaeorum
      colonies were in thermal stress conditions at the time of sample collection;
      these conditions may precede the bleaching process in zoanthids. Hence, the use
      of mucus as an indicator of this process should be evaluated in the future.

PMID- 29360532
TI  - The association between early-life relative telomere length and childhood
      neurodevelopment.
AB  - PURPOSE: To examine the association between telomere length and neurodevelopment
      in children. METHODS: We examined the relationship between relative telomere
      length (rTL) and neurodevelopmental outcomes at 9 and 30 months, and 5 years of
      age in children enrolled in the Seychelles Child Development Study Nutrition
      Cohort 1 (NC1). Relative telomere length was measured in cord blood and in child
      blood at age five. Multivariable linear regression examined associations between
      neurodevelopmental outcomes and rTL adjusting for relevant covariates. RESULTS:
      Mean rTL was 1.18 at birth and 0.71 at age five. Increased cord blood rTL was
      associated with better scores on two neurodevelopmental tests, the psychomotor
      developmental index (beta = 4.01; 95% confidence interval (CI) = 0.17, 7.85) at
      age 30 months, and the Woodcock Johnson test of achievement letter-word score
      (beta = 2.88; CI = 1.21-4.56) at age five. The Woodcock Johnson test of
      achievement letter-word score remained statistically significant after two
      outliers were excluded (beta = 2.83; CI = 0.69, 4.97); the psychomotor
      developmental index did not (beta = 3.62; CI = -1.28, 8.52). None of the
      neurodevelopmental outcomes at age five were associated with five-year rTL.
      CONCLUSION: Although increased cord blood rTL was associated with better test
      scores for a few neurodevelopmental outcomes, this study found little consistent
      evidence of an association between rTL and neurodevelopment. Future studies with
      a larger sample size, longer follow-up, and other relevant biological markers
      (e.g. oxidative stress) are needed to clarify the role of rTL in neurodevelopment
      and its relevance as a potential surrogate measure for oxidative stress in the
      field of developmental neurotoxicity.

PMID- 29360534
TI  - Immune effects of the neurotoxins ciguatoxins and brevetoxins.
AB  - Ciguatoxins (CTXs) and brevetoxins (PbTxs) are phycotoxins that can accumulate
      along the marine food chain and thus cause seafood poisoning in humans, namely
      "ciguatera fish poisoning" (CFP) and "neurotoxic shellfish poisoning" (NSP),
      respectively. CFP is characterized by early gastrointestinal symptoms and typical
      sensory disorders (paraesthesia, pain, pruritus and cold dysaesthesia), which can
      persist several weeks and, in some cases, several months or years. NSP is
      considered a mild form of CFP with similar but less severe symptoms. After
      inhaled exposure, PbTxs can also cause respiratory tract irritation in healthy
      subjects and asthma exacerbations in predisposed subjects, whose respiratory
      functions may be disrupted for several days following PbTx inhalation.
      Mechanistically, it is well established that CTX- or PbTx-induced disturbances
      are primarily mainly due to voltage-gated sodium channel activation in sensory
      and motor peripheral nervous system. However, little is known about the
      pathophysiology or a potential individual susceptibility to long lasting effects
      of CFP/NSP. In addition to their action on the nervous system, PbTxs and CTXs
      were also shown to exert effects on the immune system. However, their role in the
      pathophysiology of syndromes induced by CTX or PbTx exposure is poorly
      documented. The aim of this review is to inventory the literature thus far on the
      inflammatory and immune effects of PbTxs and CTXs.

PMID- 29360535
TI  - Microbial biotransformation of bioactive and clinically useful steroids and some
      salient features of steroids and biotransformation.
AB  - Steroids are perhaps one of the most widely used group of drugs in present day.
      Beside the established utilization as immunosuppressive, anti-inflammatory, anti
      rheumatic, progestational, diuretic, sedative, anabolic and contraceptive agents,
      recent applications of steroid compounds include the treatment of some forms of
      cancer, osteoporosis, HIV infections and treatment of declared AIDS. Steroids
      isolated are often available in minute amounts. So biotransformation of natural
      products provides a powerful means in solving supply problems in clinical trials
      and marketing of the drug for obtaining natural products in bulk amounts. If the
      structure is complex, it is often an impossible task to isolate enough of the
      natural products for clinical trials. The microbial biotransformation of steroids
      yielded several novel metabolites, exhibiting different activities. The
      metabolites produced from pregnenolone acetate by Cunning hamella elegans and
      Rhizopus stolonifer were screened against tyrosinase and cholinesterase showed
      significant inhibitory activities than the parent compound. Diosgenin and its
      transformed sarsasapogenin were screened for their acetyl cholinesterase and
      butyryl cholinesterase inhibitory activities. Sarsasapogenin was screened for
      phytotoxicity, and was found to be more active than the parent compound.
      Diosgenin, prednisone and their derivatives were screened for their anti
      leishmanial activity. All derivatives were found to be more active than the
      parent compound. The biotransformation of steroids have been reviewed to a little
      extent. This review focuses on the biotransformation and functions of selected
      steroids, the classification, advantages and agents of enzymatic
      biotransformation and examines the potential role of new enzymatically
      transformed steroids and their derivatives in the chemoprevention and treatment
      of other diseases. tyrosinase and cholinesterase inhibitory activities, severe
      asthma, rheumatic disorders, renal disorders and diseases of inflammatory bowel,
      skin, gastrointestinal tract.

PMID- 29360536
TI  - Synthesis and cytotoxic effect of pregnenolone derivatives with one or two
      alpha,beta-unsaturated carbonyls and an ester moiety at C-21 or C-3.
AB  - Four series of pregnenolone derivatives having one or two alpha,beta-unsaturated
      carbonyls and an ester moiety at C-21 or C-3 were synthetized to compare their
      cytotoxicity effect. The final compounds were evaluated on three human cancer
      cell lines: PC-3 (prostate cancer), MCF-7 (breast cancer), SKLU-1 (lung cancer)
      and a noncancerous cell line HGF (human gingival fibroblast). Two steroids with a
      4-fluorinated benzoic acid ester at C-21 were the most active against lung cancer
      cell line with IC50 of 13.1 +/- 1.2 and 12.8 +/- 0.5 MUM and showed a low
      percentage of cytotoxicity for noncancerous cells (27.63 +/- 2.3 and 18.39 +/-
      1.2% in the screening at 50 MUM).

PMID- 29360537
TI  - Photoprotection of ultraviolet-B filters: Updated review of endocrine disrupting
      properties.
AB  - The Ultraviolet (UV) radiation is emitted by the sun and is part of the
      electromagnetic spectrum. There are three types of UV rays (UV-A, UV-B and UV-C),
      however only UV-A and UV-B have biologic effects in humans, with UV-B radiation
      being primarily responsible for these effects. Among the measures of
      photoprotection advised by the health authorities, the topical application of
      sunscreens (containing UV-B filters) is the preferred worldwide. Currently,
      octylmethoxycinnamate (OMC) is the most commonly used UV-B filter in sunscreens.
      Their application has proven to be effective in preventing burns, but its
      efficiency against melanoma continues under intense controversy. Studies have
      shown that OMC behaves like an endocrine disruptor, altering the normal
      functioning of organisms. However, few studies have evaluated their multiple
      hormonal activities. Some studies suggest that the OMC exerts an estrogenic, anti
      androgenic, anti-progestenic and anti-thyroid activity. But, through what
      mechanisms? In humans, few studies were performed, and some questions remain
      unclear. Thus, the purpose of this review is to present the multiple hormonal
      activities established for the OMC, making a critical analysis and relationship
      between the effects in cells, animals and humans.

PMID- 29360538
TI  - CCRK is a novel signalling hub exploitable in cancer immunotherapy.
AB  - Cyclin-dependent kinase 20 (CDK20), or more commonly referred to as cell cycle
      related kinase (CCRK), is the latest member of CDK family with strong linkage to
      human cancers. Accumulating studies have reported the consistent overexpression
      of CCRK in cancers arising from brain, colon, liver, lung and ovary. Such
      aberrant up-regulation of CCRK is clinically significant as it correlates with
      tumor staging, shorter patient survival and poor prognosis. Intriguingly, the
      signalling molecules perturbed by CCRK are divergent and cancer-specific,
      including the cell cycle regulators CDK2, cyclin D1, cyclin E and RB in
      glioblastoma, ovarian carcinoma and colorectal cancer, and KEAP1-NRF2
      cytoprotective pathway in lung cancer. In hepatocellular carcinoma (HCC), CCRK
      mediates virus-host interaction to promote hepatitis B virus-associated
      tumorigenesis. Further mechanistic analyses reveal that CCRK orchestrates a self
      reinforcing circuitry comprising of AR, GSK3beta, beta-catenin, AKT, EZH2, and NF
      kappaB signalling for transcriptional and epigenetic regulation of oncogenes and
      tumor suppressor genes. Notably, EZH2 and NF-kappaB in this circuit have been
      recently shown to induce IL-6 production to facilitate tumor immune evasion.
      Concordantly, in a hepatoma preclinical model, ablation of Ccrk disrupts the
      immunosuppressive tumor microenvironment and enhances the therapeutic efficacy of
      immune checkpoint blockade via potentiation of anti-tumor T cell responses. In
      this review, we summarized the multifaceted tumor-intrinsic and -extrinsic
      functions of CCRK, which represents a novel signalling hub exploitable in cancer
      immunotherapy.

PMID- 29360539
TI  - Discovery of Leonuri and therapeutical applications: From bench to bedside.
AB  - Despite several advances in percutaneous coronary intervention and the discovery
      of new drugs, the incidence of myocardial infarction and deaths due to
      cardiovascular diseases (CVD) has not decreased markedly in China. The quality of
      life is affected seriously, which further results in great social and family
      burden. Many drugs, from the century-old aspirin to the newly FDA-approved
      Byvalson, have been proven to be effective in the treatment and prevention of
      CVD. As clinically reported, those life-saving drugs still have their side
      effects in regards to the narrow therapeutic indexes influenced by individual
      genetic variations. Herba Leonuri, also known as Chinese Motherwort, which are
      naturally present in plants and traditionally are used for the uterotonic action,
      postpartum blood stasis, breast pain as well as other gynecological disorders in
      China for thousands of years. Since the last two decades, our group has reported
      leonurine, a unique alkaloid found in Herba Leonuri, exhibits various
      bioactivities such as antioxidant, anti-apoptotic effects, free radical
      scavenging and anti-inflammatory effects, in addition to improving micro
      circulation. These bioactivities are related to the underlying mechanisms of
      ischemic heart diseases and cardiac fibrosis. Pharmacological studies have proven
      leonurine to be effective in treating CVD in various ways, particularly ischemic
      heart diseases. Besides the cardio protective effects, which are similar in the
      central nervous system, more specifically, inhibited mitochondrial reactive
      oxygen species production together with the restored mitochondrial function and
      redox state were observed in middle cerebral artery occlusion rats by leonurine
      treatment, which strongly reveals its neuroprotective effects and carries a
      therapeutic potential for recovery and prevention of stroke. Based on their mode
      of action, we propose that leonurine can be developed as drugs to treat ischemic
      heart diseases. Taking advantage of the most recent findings in pharmacological
      research including the effects of low toxicity and good pharmacokinetics
      characteristics, leonurine has a very attractive prospect of clinical
      application. Our recent promising pharmacological results may be able to
      eradicate the barrier hindering its sale on market. In sum, from bench to bedside
      is no longer a long way for leonurine.

PMID- 29360541
TI  - Methionine hydroxy analogue supplementation modulates gill immunological and
      barrier health status of grass carp (Ctenopharyngodon idella).
AB  - This study was conducted to investigate the effects of methionine hydroxy
      analogue (MHA) on the physical barrier and immune defence in the gill of young
      grass carp (Ctenopharyngodon idella). A total 630 young grass carp with an
      average initial weight of 259.70 +/- 0.47 g were fed graded levels of MHA (0,
      2.4, 4.4, 6.4, 8.5 and 10.5 g/kg diet) and one DL-methionine (DLM) group (6.4
      g/kg diet) for 8 weeks. After feeding trial, 15 fish from each treatment were
      challenged with Flavobacterium columnare. Compared to the basal diet, optimal MHA
      improved cellular structure integrity of gill via repressing death receptor and
      mitochondria pathways induced apoptosis, which might be related to the down
      regulation of c-Jun-N-terminal kinase mRNA levels (P < .05). Simultaneously,
      optimal MHA supplementation improved cellular structure integrity of gill via
      elevating glutathione contents, antioxidant enzymes activities and corresponding
      isoforms mRNA levels to attenuate oxidative damage, which might be to the up
      regulation of NF-E2-related factor 2 mRNA levels and down-regulation of Kelch
      like ECH-associating protein 1a mRNA levels (P < .05). Besides, optimal MHA
      improved intercellular structure integrity of immune organs via up-regulating the
      mRNA levels of intercellular tight junctions-related genes, which might be owing
      to the down-regulation of myosin light chain kinase (MLCK) mRNA levels (P < .05).
      Summarily, MHA could improve the physical barrier of fish gill. In addition,
      optimal MHA supplementation increased lysozyme (LZ) and acid phosphatase (ACP)
      activities, complement 3 (C3), C4 and immunoglobulin M contents and up-regulated
      mRNA levels of liver-expressed antimicrobial peptide 2, hepcidin and beta
      defensin, suggesting that MHA could enhance antimicrobial ability of fish gill.
      Meanwhile, optimal MHA supplementation enhanced the immune defence of gill via
      down-regulating pro-inflammatory cytokines mRNA levels and up-regulated anti
      inflammatory cytokines mRNA levels, which might be attributed to the down
      regulation of nuclear factor kappaB p65, c-Rel, IkappaB kinase beta, p38 mitogen
      activated protein kinase, eIF4E-binding protein1 (4E-BP1) and 4E-BP2 mRNA levels
      and up-regulation of inhibitor of kappaBalpha, ribosomal protein S6 kinase 1 and
      target of rapamycin mRNA levels (P < .05). In conclusion, the positive effect of
      MHA on gill health is associated with the improvement of the defence against
      apoptosis, antioxidant status, tight junctions and immune defence of fish gill.
      Meanwhile, MHA was superior to DLM on improving the physical barrier of fish
      gill. For the direction to healthy breeding of young grass carp, the optimal MHA
      supplementation levels on the premise of 4.01 g/kg methionine basal were
      estimated by quadratic regression curve, such as 5.49, 6.17 and 6.02 g/kg diet
      bases on the defence against gill-rot, malondialdehyde content and LZ activity in
      the gill, respectively.

PMID- 29360542
TI  - Growth performance, blood health, antioxidant status and immune response in red
      sea bream (Pagrus major) fed Aspergillus oryzae fermented rapeseed meal (RM
      Koji).
AB  - This study evaluated the effects of dietary substitution of fishmeal by graded
      levels of a blend composed of Aspergillus oryzae fermented rapeseed meal [0%
      (RM0), 25% (RM25), 50% (RM50), 75% (RM75) and 100% (RM100)] on growth
      performance, haemato-immunological responses and antioxidative status of Pagrus
      major (average weight 5.5 +/- 0.02 g). After 56 days, growth performances were
      significantly improved in fish fed RM25 diet compared to control (P < 0.05).
      Meanwhile, up to 50% replacement of fishmeal did not affect growth performance,
      feed conversion efficiency, protein efficiency ratio, protein apparent
      digestibility, protease activity, fish somatic indices and survival compared to
      control. While blood hematocrit and plasma protein were significantly enhanced in
      groups fed RM0 and RM25 diets, most of the hematological parameters did not
      change through the trial except glutamic pyruvate transaminase which was
      significantly increased in RM75 and RM100 groups and blood cholesterol which was
      gradually decreased with the increasing level of the blend. Interestingly,
      feeding fish with RM25 and RM50 diets significantly showed enhanced lysozyme,
      bactericidal and peroxidase activities and fish fed the same diets showed high
      resistance against oxidative stress (biological antioxidant potential and
      reactive oxygen metabolites). Additionally, catalase activity and tolerance
      against low salinity seawater were higher in fish fed RM25 diet. These findings
      suggested that, at a moderate level (25% and 50%), substitution of fishmeal by
      the fermented rapeseed meal promoted growth, nutrient utilization, and exerted
      immune responses and anti-oxidative effects in red sea bream.

PMID- 29360540
TI  - The sigma-1 receptor as a regulator of dopamine neurotransmission: A potential
      therapeutic target for methamphetamine addiction.
AB  - Methamphetamine (METH) abuse is a major public health issue around the world, yet
      there are currently no effective pharmacotherapies for the treatment of METH
      addiction. METH is a potent psychostimulant that increases extracellular dopamine
      levels by targeting the dopamine transporter (DAT) and alters neuronal activity
      in the reward centers of the brain. One promising therapeutic target for the
      treatment of METH addiction is the sigma-1 receptor (sigma1R). The sigma1R is an
      endoplasmic reticulum-localized chaperone protein that is activated by cellular
      stress, and, unique to this chaperone, its function can also be induced or
      inhibited by different ligands. Upon activation of this unique "chaperone
      receptor", the sigma1R regulates a variety of cellular functions and possesses
      neuroprotective activity in the brain. Interestingly, a variety of sigma1R
      ligands modulate dopamine neurotransmission and reduce the behavioral effects of
      METH in animal models of addictive behavior, suggesting that the sigma1R may be a
      viable therapeutic target for the treatment of METH addiction. In this review, we
      provide background on METH and the sigma1R as well as a literature review
      regarding the role of sigma1Rs in modulating both dopamine neurotransmission and
      the effects of METH. We aim to highlight the complexities of sigma1R pharmacology
      and function as well as the therapeutic potential of the sigma1R as a target for
      the treatment of METH addiction.

PMID- 29360543
TI  - Coupling corticotropin-releasing-hormone and angiotensin converting enzyme 2
      dampens stress responsiveness in male mice.
AB  - This study used mice to evaluate whether coupling expression of corticotropin
      releasing hormone (CRH) and angiotensin converting enzyme 2 (ACE2) creates
      central interactions that blunt endocrine and behavioral responses to psychogenic
      stress. Central administration of diminazene aceturate, an ACE2 activator, had no
      effect on restraint-induced activation of the hypothalamic-pituitary-adrenal
      (HPA) axis; however, mice that ubiquitously overexpress ACE2 had reduced plasma
      corticosterone (CORT) and pituitary expression of POMC mRNA. The Cre-LoxP system
      was used to restrict ACE2 overexpression to CRH synthesizing cells and probe
      whether HPA axis suppression was the result of central ACE2 and CRH interactions.
      Within the paraventricular nucleus of the hypothalamus (PVN), mice with ACE2
      overexpression directed to CRH had a ~2.5 fold increase in ACE2 mRNA, which co
      localized with CRH mRNA. Relative to controls, mice overexpressing ACE2 in CRH
      cells had a decreased CORT response to restraint as well as decreased CRH mRNA in
      the PVN and CEA and POMC mRNA in the pituitary. Administration of ACTH similarly
      increased plasma CORT, indicating that the blunted HPA axis activation that
      accompanies ACE2 overexpression in CRH cells is centrally mediated. Anxiety-like
      behavior was assessed to determine whether the decreased HPA axis activation was
      predictive of anxiolysis. Mice with ACE2 overexpression directed to CRH cells
      displayed decreased anxiety-like behavior in the elevated plus maze and open
      field when compared to that of controls. Collectively, these results suggest that
      exogenous ACE2 suppresses CRH synthesis, which alters the central processing of
      psychogenic stress, thereby blunting HPA axis activation and attenuating anxiety
      like behavior.

PMID- 29360545
TI  - Structural characterization and antioxidant activity of polysaccharide from
      ginger.
AB  - Two components ginger polysaccharide 1 (GP1) and ginger polysaccharide 2 (GP2)
      were extracted. The results showed that the molecular weights of GP1 and GP2 were
      6128 Da and 12,619 Da, respectively. The composition and proportion of GP1 and
      GP2 were mannose, glucose and galactose in a molar ratio of 4.96: 92.24: 2.80 and
      arabinose, mannose, glucose and galactose in a molar ratio of 4.78: 16.70: 61.77:
      16.75, respectively, illustrating that GP1 and GP2 were not a kind of
      homopolysaccharide. GP1 has a three-helix structure, and the structure is closely
      linked. GP2 contains sulfuric acid groups, and has a high oxidation resistance,
      its structure is more evacuated and messy.

PMID- 29360546
TI  - Polyaniline/multiwall carbon nanotubes/starch nanocomposite material and
      hemoglobin modified carbon paste electrode for hydrogen peroxide and glucose
      biosensing.
AB  - This paper describes the application of novel nanocomposite material
      polyaniline/multiwall carbon nanotubes/starch (designated as PCS) as a good
      electrode material for electrochemical sensing. The developed ternary composite
      system has manifold interactions and synergistic improved properties - high
      surface area, good electro-activity, conductivity, stable dispersion,
      biocompatible, hydrophilic and hydrophobic regions, multifunctional, and
      nanoturmeric shape morphology. Hydrogen peroxide biosensor was fabricated as a
      model system using PCS and hemoglobin (HB) modified carbon paste electrode. PCS
      and HB compatible and effectively communicate with each other, facilitate the
      charge transfer (potassium ferricyanide used as electroactive marker). Thus, PCS
      and HB (in combination) is a good electrode material for sensitive and selective
      detection of peroxide. The developed biosensor showed a linear range (0.1 mM-5
      mM, R2 = 0.9975), limit of detection (0.032 mM), sensitivity (76.43 MUA/mM cm2)
      and long-term storage and stability. This material could be used a platform to
      develop some other sensors by using other redox enzymes. As a model, we
      incorporate glucose oxidase to detect Glucose. Thus, the favorable properties
      indicate that the proposed material system suitable for low-cost sensor strips.

PMID- 29360544
TI  - Circulating tumor cell-derived organoids: Current challenges and promises in
      medical research and precision medicine.
AB  - Traditional 2D cell cultures do not accurately recapitulate tumor heterogeneity,
      and insufficient human cell lines are available. Patient-derived xenograft (PDX)
      models more closely mimic clinical tumor heterogeneity, but are not useful for
      high-throughput drug screening. Recently, patient-derived organoid cultures have
      emerged as a novel technique to fill this critical need. Organoids maintain tumor
      tissue heterogeneity and drug-resistance responses, and thus are useful for high
      throughput drug screening. Among various biological tissues used to produce
      organoid cultures, circulating tumor cells (CTCs) are promising, due to relative
      ease of ascertainment. CTC-derived organoids could help to acquire relevant
      genetic and epigenetic information about tumors in real time, and screen and test
      promising drugs. This could reduce the need for tissue biopsies, which are
      painful and may be difficult depending on the tumor location. In this review, we
      have focused on advances in CTC isolation and organoid culture methods, and their
      potential applications in disease modeling and precision medicine.

PMID- 29360547
TI  - Properties of PHA bi-, ter-, and quarter-polymers containing 4-hydroxybutyrate
      monomer units.
AB  - The present study investigates physicochemical, mechanical, and biological
      properties of polyhydroxyalkanoate (PHA) copolymers containing 4-hydroxybutyrate
      (4HB) synthesized in Cupriavidus eutrophus B10646 culture. In poly(3
      hydroxybutyrate/4-hydroxybutyrate) [P(3HB/4HB)] bipolymers, 4HB varied between
      10.4 and 75.0 mol%; in poly(3-hydroxybutyrate/3-hydroxyvalerate/4
      hydroxybutyrate) terpolymers, 4HB constituted 28.7-55.6 mol%; and in poly(3
      hydroxybutyrate/3-hydroxyvalerate/4-hydroxybutyrate/3-hydroxyhexanoate)
      quaterpolymers, 4HB varied between 9.3 and 13.3 mol%. The degree of crystallinity
      of P(3HB/4HB) copolymers decreased consistently with an increase in 4HB content,
      reaching 38%. The incorporation of 3-hydroxyvalerate and 3-hydroxyhexanoate into
      copolymers enhanced that effect. The effect of 4HB monomer units on temperature
      properties of copolymers was exhibited as lowering of the melting temperature and
      crystallization temperature, which improved the processing-related properties of
      the copolymers. All copolymers containing 4HB showed enhanced elongation at break
      compared to poly(3-hydroxybutyrate). Polymer films prepared from PHAs with
      different chemical composition had similar microstructure and porosity and had no
      toxic effect on mouse fibroblast NIH 3 T3 cells, proving their high
      biocompatibility.

PMID- 29360548
TI  - Inhibition of lysozyme fibrillogenesis by hydroxytyrosol and dopamine: An Atomic
      Force Microscopy study.
AB  - Protein aggregation underlies many human diseases characterized by the deposition
      of normally soluble proteins in both fibrillar and amorphous aggregates. Here,
      Atomic Force Microscopy (AFM) has been applied to investigate the ability to
      inhibit hen egg white lysozyme (HEWL) fibrillogenesis by hydroxytyrosol (HT), one
      of the main phenolic components of olive oil. In this framework, HEWL is a useful
      and well-studied model protein whose amyloid-like fibril formation can be induced
      under experimental conditions where HT is more stable. HEWL fibrils, obtained at
      pH 1.6 and at 65  degrees C, exhibited a height of about 3 nm and a fibril length
      on average of about 3 MUm. The presence of HT reduced the HEWL fibril number and
      length with respect to the control sample. Interestingly, also dopamine, a
      compound with a chemical structure similar to HT, decreased both the fibril
      number and the fibril length. AFM experimental data were supported by Thioflavin
      T assay and Fourier transform infrared spectroscopy. Our results show that HT is
      an effective inhibitor of HEWL aggregation, thus suggesting possible future
      applications of this natural compound for potential prevention or treatment of
      amyloid diseases, or as a lead molecular structure for the design of improved
      modulators.

PMID- 29360549
TI  - Development and validation of a quantitative PCR assay for detection of Emydoidea
      herpesvirus 1 in free-ranging Blanding's turtles (Emydoidea blandingii).
AB  - Blanding's turtles (Emydoidea blandingii), an endangered species in Illinois,
      have experienced range-wide declines because of habitat degradation and
      fragmentation, predation, and road mortality. While ongoing studies are crucial
      to a thorough understanding of the natural history and demographics in these
      disjointed Illinois populations, infectious disease threats have been largely
      unevaluated. Herpesvirus outbreaks have been associated with high morbidity and
      mortality in populations of captive tortoises and turtles worldwide, including
      the family Emydidae (pond and box turtles). However, novel herpesviruses
      including Terrapene herpesvirus 1, Emydid herpesvirus 1 and 2, and Glyptemys
      herpesvirus 1 and 2, have recently been identified in apparently healthy free
      ranging freshwater turtles. In 2015, 20 free-ranging Blanding's turtles in DuPage
      County, Illinois were screened for a herpesvirus using consensus PCR. A novel
      herpesvirus species (Emydoidea herpesvirus 1; EBHV1) was identified in two
      animals and shared a high degree of sequence homology to other freshwater turtle
      herpesviruses. Two quantitative real-time PCR assays, using EBHV1 primer-1 and
      primer-2, were developed to target an EBHV1-specific segment of the DNA-dependent
      DNA polymerase gene and validated. Both assays performed with high efficiency
      (slope = -3.2; R2 = 1), low intra-assay variability, and low inter-assay
      variability (coefficient of variation <2% at all dilutions). However, EBHV1
      primer-2 displayed less variation and was selected to test clinical samples and
      five closely related herpesvirus control samples. Results indicate that this
      assay is specific for EBHV1, has a linear range of detection from 108 to 101
      viral copies per reaction, and can categorically detect as few as 1 viral copy
      per reaction. This qPCR assay provides a valuable diagnostic tool for future
      characterization of EBHV1 epidemiology.

PMID- 29360551
TI  - Reply to: "The role of NAFLD in extrahepatic malignancies: The importance of
      ruling out the effect of obesity".

PMID- 29360550
TI  - Genomic characterization of biliary tract cancers identifies driver genes and
      predisposing mutations.
AB  - BACKGROUND & AIMS: Biliary tract cancers (BTCs) are clinically and pathologically
      heterogeneous and respond poorly to treatment. Genomic profiling can offer a
      clearer understanding of their carcinogenesis, classification and treatment
      strategy. We performed large-scale genome sequencing analyses on BTCs to
      investigate their somatic and germline driver events and characterize their
      genomic landscape. METHODS: We analyzed 412 BTC samples from Japanese and Italian
      populations, 107 by whole-exome sequencing (WES), 39 by whole-genome sequencing
      (WGS), and a further 266 samples by targeted sequencing. The subtypes were 136
      intrahepatic cholangiocarcinomas (ICCs), 101 distal cholangiocarcinomas (DCCs),
      109 peri-hilar type cholangiocarcinomas (PHCs), and 66 gallbladder or cystic duct
      cancers (GBCs/CDCs). We identified somatic alterations and searched for driver
      genes in BTCs, finding pathogenic germline variants of cancer-predisposing genes.
      We predicted cell-of-origin for BTCs by combining somatic mutation patterns and
      epigenetic features. RESULTS: We identified 32 significantly and commonly mutated
      genes including TP53, KRAS, SMAD4, NF1, ARID1A, PBRM1, and ATR, some of which
      negatively affected patient prognosis. A novel deletion of MUC17 at 7q22.1
      affected patient prognosis. Cell-of-origin predictions using WGS and epigenetic
      features suggest hepatocyte-origin of hepatitis-related ICCs. Deleterious
      germline mutations of cancer-predisposing genes such as BRCA1, BRCA2, RAD51D,
      MLH1, or MSH2 were detected in 11% (16/146) of BTC patients. CONCLUSIONS: BTCs
      have distinct genetic features including somatic events and germline
      predisposition. These findings could be useful to establish treatment and
      diagnostic strategies for BTCs based on genetic information. LAY SUMMARY: We here
      analyzed genomic features of 412 BTC samples from Japanese and Italian
      populations. A total of 32 significantly and commonly mutated genes were
      identified, some of which negatively affected patient prognosis, including a
      novel deletion of MUC17 at 7q22.1. Cell-of-origin predictions using WGS and
      epigenetic features suggest hepatocyte-origin of hepatitis-related ICCs.
      Deleterious germline mutations of cancer-predisposing genes were detected in 11%
      of patients with BTC. BTCs have distinct genetic features including somatic
      events and germline predisposition.

PMID- 29360552
TI  - The role of NAFLD in extrahepatic malignancies: The importance of ruling out the
      effect of obesity.

PMID- 29360553
TI  - Endothelial JAK2V617F does not enhance liver lesions in mice with Budd-Chiari
      syndrome.

PMID- 29360555
TI  - Pilot study of EEG in neonates born to mothers with gestational diabetes
      mellitus.
AB  - BACKGROUND: The goal was to evaluate whether there was neurodevelopmental
      deficits in newborns born to mothers with gestational diabetes mellitus (GDM)
      compared to control newborns born to healthy mothers. METHODS: Forty-six pregnant
      women (21 controls and 25 GDM) were recruited. Electroencephalogram (EEG) was
      recorded in the newborns within 48 h after birth. The EEG signal was
      quantitatively analyzed using power spectral density (PSD); coherence between
      hemispheres was calculated in paired channels of frontal, temporal, central and
      occipital regions. RESULTS: The left centro-occipital PSD in control newborns was
      12% higher than in GDM newborns (p = 0.036) but was not significant after
      adjustment for gestational age. While coherence was higher in the frontal regions
      compared to the occipital regions (p < 0.001), there was no difference between
      the groups for the fronto-temporal, frontal-central, centro-occipital and tempo
      occipital regions. CONCLUSION: Our results support that EEG differences between
      groups were mainly modified by gestational age and less by GDM status of the
      mothers. However, there is a need to confirm this result with a higher number of
      mother-newborns. Quantitative EEG in GDM newborns within 48 h after birth is
      feasible. This study emphasizes the importance of controlling blood glucose
      during GDM to protect infant brain development.

PMID- 29360556
TI  - Dietary polyphenols: Structures, bioavailability and protective effects against
      atherosclerosis.
AB  - Epidemiological studies have demonstrated that nutritional habits, like those
      based on high consumption of fruits and vegetables, have been associated with a
      longer life expectancy and a significant decrease in the incidence and prevalence
      of several chronic diseases with inflammatory basis, such as cardiovascular
      diseases (CVD). This beneficial activity has been related to the content of
      several bioactive compounds in fruit and vegetables, such as polyphenols. The
      cardioprotective effects of polyphenols have been linked mainly to its
      antioxidant properties; however, recent findings attribute its anti
      atherosclerotic potential to modulate simultaneous signaling and mechanistic
      pathways. Emerging data suggest that polyphenols can regulate cellular lipid
      metabolism; vascular and endothelial function; haemostasis; as well as platelet
      function; which represent primary conditions for atherosclerotic plaque formation
      and development. This review presents the results of a selection of experimental
      studies and clinical trials regarding the atheroprotective effects of the most
      common dietary polyphenols.

PMID- 29360557
TI  - Peroxiredoxins in inflammatory liver diseases and ischemic/reperfusion injury in
      liver transplantation.
AB  - Peroxiredoxins (Prxs) belong to the superfamily of thiol-dependent peroxidases,
      and remove reactive oxygen species (ROS) and other oxidative stress products. The
      expression and activity of Prxs can be substantially affected by stimuli from the
      microenvironment, and in turn regulate cytokine secretion in the context of
      inflammation in both peroxidase-dependent and -independent pathways. Prxs
      translocate to mitochondria and are hyperoxidized during acute liver damage, and
      attenuate intracellular ROS accumulation through their peroxidase activity. In
      particularly, Prx1 modulates the microenvironment in liver injuries by reducing
      adhesion molecule expression in vascular endothelial cells and inhibiting the
      inflammatory response and adhesion of macrophages. Prxs have potent prosurvival
      effects against ROS in ischemic/reperfusion (I/R) injury, but Prxs released from
      necrotic cells increase secretion of inflammatory cytokines by macrophages
      through TLR2 and 4 activation, which promotes cell death. Prxs can be used as
      biomarkers to evaluate I/R injury and predict graft survival in liver
      transplantation. Prxs are modulated in various types of chronic hepatitis and
      hepatosteatosis, and mediate disease progression. Alcohol administration
      increases oxidization and inactivation of Prxs in mice because of oxidative
      stress. In conclusion, Prxs are essential mediators and biomarkers in
      inflammatory liver diseases and I/R injury.

PMID- 29360554
TI  - Circadian regulation of renal function.
AB  - The kidneys regulate many vital functions that require precise control throughout
      the day. These functions, such as maintaining sodium balance or regulating
      arterial pressure, rely on an intrinsic clock mechanism that was commonly
      believed to be controlled by the central nervous system. Mounting evidence in
      recent years has unveiled previously underappreciated depth of influence by
      circadian rhythms and clock genes on renal function, at the molecular and
      physiological level, independent of other external factors. The impact of
      circadian rhythms in the kidney also affects individuals from a clinical
      standpoint, as the loss of rhythmic activity or clock gene expression have been
      documented in various cardiovascular diseases. Fortunately, the prognostic value
      of examining circadian rhythms may prove useful in determining the progression of
      a kidney-related disease, and chronotherapy is a clinical intervention that
      requires consideration of circadian and diurnal rhythms in the kidney. In this
      review, we discuss evidence of circadian regulation in the kidney from basic and
      clinical research in order to provide a foundation on which a great deal of
      future research is needed to expand our understanding of circadian relevant
      biology.

PMID- 29360558
TI  - Dynamics of social behaviour at parturition in a gregarious ungulate.
AB  - Group living is the behavioural response that results when individuals assess the
      costs vs benefits of sociality, and these trade-offs vary across an animal's
      life. Here we quantitatively assess how periparturient condition (mother/non
      mother) and births affect the dynamics of social interactions of a gregarious
      ungulate, and how such can help to explain evolutionary hypotheses of the mother
      offspring bond. To achieve this we used data of the individual movement of a
      group of Scottish blackface sheep (Ovis aries) marked with GPS collars and
      properties of mathematical graphs (networks). Euclidean pair-wise distance
      between sheep were threshold at different percentiles to determine network links,
      and these thresholds have a profound effect on the connectivity of the resulting
      network. Births increased the average pair-wise distance between mothers, and
      between mothers and non-mothers, with less effect on the distance between non
      mothers. Mothers occupied peripheral positions within the flock, more evident
      following births. Associations between individuals (i.e. network community
      change) were highly dynamic, though mothers were less likely to change community
      than non-mothers, especially after births. Births hampered individual
      communication within the flock (assessed via network closeness centrality),
      especially in mothers. Overall leadership (lead positioning relative to flock
      movement) was not associated to reproductive condition, and individual leadership
      rank was not affected by births. A ten minute GPS acquisition time was adequate
      to capture complex social dynamics in sheep movement. The results on mother's
      isolation behaviour support the hypotheses of selection for maternal imprint
      facilitation, reducing risks to nursing alien offspring, and group/multilevel
      selection on group formation.

PMID- 29360559
TI  - A mapping of 115,000 randomized trials revealed a mismatch between research
      effort and health needs in non-high-income regions.
AB  - BACKGROUND: Concerns exist as to whether the allocation of resources in clinical
      research is aligned with public health needs. We evaluated the alignment between
      the effort of clinical research through the conduct of randomized controlled
      trials (RCTs) and health needs measured as the burden of diseases for all regions
      and a broad range of diseases. METHODS: We grouped countries into seven regions
      and diseases into 27 groups. We mapped all RCTs initiated between 2006 and 2015
      that were registered at the WHO International Clinical Trials Registry Platform
      to regions and diseases. The burden of diseases in 2005 was mapped as disability
      adjusted life years (DALYs), based on the 2010 Global Burden of Diseases study.
      Within regions, we defined a research gap when the proportion of RCTs concerning
      a disease in the region was less than half the relative burden of the disease.
      RESULTS: We mapped 117,180 RCTs planning to enroll 42.6 million patients and
      2,220 million DALYs. In high- versus non-high-income countries, 130.9 versus 6.9
      RCTs per million DALYs were conducted. We did not identify any research gap in
      high-income countries. We identified research gaps for all other regions. In
      particular, for Sub-Saharan Africa, we identified research gaps for common
      infectious diseases (CID) and neonatal disorders (ND): 5.8% (95% uncertainty
      interval 4.7-6.9) and 2.0% (0.9-4.5) of RCTs in Sub-Saharan Africa concerned CID
      and ND, although these diseases represented 22.9% and 11.6% of the burden in the
      region, respectively. For South Asia, we identified research gaps for the same
      two groups of diseases. CONCLUSIONS: In non-high-income regions, the conduct of
      RCTs was misaligned with the distribution of major causes of burden, in
      particular infectious diseases and neonatal disorders in Sub-Saharan Africa and
      South Asia.

PMID- 29360560
TI  - Dual-responsive lidocaine in situ gel reduces pain of intrauterine device
      insertion.
AB  - The most effective and safe contraceptive method, intrauterine devices (IUDs), is
      still underutilized due to the pain barrier during IUD insertion. Lidocaine, a
      well-known local anesthetic, can be used to relieve IUD insertion pain. This
      study aimed at formulation, in vitro, in vivo and clinical evaluation of a novel
      lidocaine dual-responsive in situ gel. Pluronic and Gelrite(r) were used as
      thermosenstive and ion-activated polymers, respectively. In situ gels containing
      2% lidocaine, pluronics and/or Gelrite(r) were prepared. The optimized dual
      responsive formula (F5) was clear, with 95% drug content, free flowing at room
      temperature and gel at vaginal temperature (Tgel of 28  degrees C). This
      optimized dual-responsive in situ gel was found to be superior to single
      responsive one due to presence of Gelrite(r), imparting resistance to dilution
      effect of simulated vaginal fluids. DSC thermograms revealed no interaction
      between formulation components. Biocompatibility study showed no degeneration,
      necrosis or inflammation. Optimized dual-responsive in situ gel was further
      evaluated for pain reduction efficiency via a pilot randomized, double-blinded,
      placebo-controlled clinical trial showing ease of self-administeration by
      patients and significant pain reduction induced at all steps of IUD insertion. In
      conclusion, lidocaine dual-responsive in situ gel can be effectively used in
      prevention of pain during IUD insertion.

PMID- 29360561
TI  - Epigenetic and epitranscriptomic changes in colorectal cancer: Diagnostic,
      prognostic, and treatment implications.
AB  - A cancer cell is the final product of a complex mixture of genetic, epigenetic
      and epitranscriptomic alterations, whose final interplay contribute to cancer
      onset and progression. This is specifically true for colorectal cancer, a tumor
      with a strong epigenetic component, which acts earlier than any other genetic
      alteration in promoting cancer cell malignant transformation. The pattern of
      progressive, and usually subtype-specific, DNA and histone modifications that
      occur in colorectal cancer has been extensively studied in the last decade,
      providing plenty of data to explore. For this tumor, it became recently evident
      that also RNA modifications play a relevant role in the activation of oncogenes
      or repression of tumor suppressor genes. In this review we provide a brief
      overview of all epigenetic and epitranscriptomic changes that have been found
      associated to colorectal cancer till now. We explore the impact of these
      alterations in cancer prognosis and response to treatment and discuss their
      potential use as cancer biomarkers.

PMID- 29360562
TI  - Haptic recognition memory following short-term visual deprivation: Behavioral and
      neural correlates from ERPs and alpha band oscillations.
AB  - In the current study, we investigated the effects of short-term visual
      deprivation (2 h) on a haptic recognition memory task with familiar objects.
      Behavioral data, as well as event-related potentials (ERPs) and induced event
      related oscillations (EROs) were analyzed. At the behavioral level, deprived
      participants showed speeded reaction times to new stimuli. Analyses of ERPs
      indicated that starting from 1000 ms the recognition of old objects elicited
      enhanced positive amplitudes only for the visually deprived group. Visual
      deprivation also influenced EROs. In this sense, we observed reduced power in the
      lower-1 alpha band for the processing of new compared to old stimuli between 500
      and 750 ms. Overall, our data showed improved haptic recognition memory after a
      short period of visual deprivation. These effects were thought to reflect a
      compensatory mechanism that might have developed as an adaptive strategy for
      dealing with the environment when visual information is not available.

PMID- 29360564
TI  - Prenatal mercury exposure and birth weight.
AB  - Adverse effects of prenatal mercury exposure on pregnancy outcomes remain a
      public health concern. We assessed the relationship between prenatal mercury
      exposure and newborn anthropometric characteristics in 334 mother-child pairs
      from the early stages of pregnancy to delivery in Tokyo, Japan, between December
      2010 and October 2012. We found a negative correlation between blood mercury
      levels during the first and second trimesters of gestation and birth weight (r = 
      0.134 and -0.119, respectively; p < 0.05). Multiple linear regression analysis
      confirmed the relationship between first-trimester maternal blood mercury levels
      and birth weight when adjusted for independent variables (beta = -0.170, t = 
      2.762; p = 0.006). Mean mercury levels in umbilical cord blood were twice as high
      as maternal blood levels (10.15 +/- 7.74 and 4.97 +/- 3.25 MUg/L, respectively; r
      = 0.974, p < 0.001). Our findings suggest that pregnant women and women of
      reproductive age should avoid mercury exposure, even at low levels, because of
      its potentially adverse effects on fetal development.

PMID- 29360563
TI  - Adrenergic receptor stimulation suppresses oxidative metabolism in isolated rat
      islets and Min6 cells.
AB  - Insulin secretion is stimulated by glucose metabolism and inhibited by
      catecholamines through adrenergic receptor stimulation. We determined whether
      catecholamines suppress oxidative metabolism in beta-cells through adrenergic
      receptors. In Min6 cells and isolated rat islets, epinephrine decreased oxygen
      consumption rates compared to vehicle control or co-administration of epinephrine
      with alpha2-adrenergic receptor antagonist yohimbine. Epinephrine also decreased
      forskolin-stimulated oxygen consumption rates, indicating cAMP dependent and
      independent actions. Furthermore, glucose oxidation rates were decreased with
      epinephrine, independent of the exocytosis of insulin, which was blocked with
      yohimbine. We evaluated metabolic targets through proteomic analysis after 4 h
      epinephrine exposure that revealed 466 differentially expressed proteins that
      were significantly enriched for processes including oxidative metabolism, protein
      turnover, exocytosis, and cell proliferation. These results demonstrate that
      acute alpha2-adrenergic stimulation suppresses glucose oxidation in beta-cells
      independent of nutrient availability and insulin exocytosis, while cAMP
      concentrations are elevated. Proteomics and immunoblots revealed changes in
      electron transport chain proteins that were correlated with lower metabolic
      reducing equivalents, intracellular ATP concentrations, and altered mitochondrial
      membrane potential implicating a new role for adrenergic control of mitochondrial
      function and ultimately insulin secretion.

PMID- 29360565
TI  - Pathogenesis and inflammatory response in experimental caprine mastitis due to
      Staphylococcus chromogenes.
AB  - Coagulase-negative staphylococci (CNS) are the most frequently isolated bacteria
      in cases of subclinical mastitis in dairy cows. CNS species may differ in their
      pathogenicity, but very little is known about their virulence factors or their
      immune response in intramammary infections. To our knowledge, no experimental
      studies into the mastitis pathogenesis caused by CNS have been described in
      lactating goats. The aim of this study was to induce an experimentally
      Staphylococcus chromogenes mastitis in lactating goats aimed at verifying if the
      model can be used to evaluate the inflammatory response, the dynamics of
      infection and the pathological findings within the first hours of intramammary
      inoculation. Six Saanen goats in mid-lactation were inoculated with 1 * 107
      colony forming units of S. chromogenes. Bacterial growth peaked in milk from the
      challenged right halves of the mammary glands (RMG) at 4 h post inoculation (PI).
      Shedding of viable bacteria showed a marked decrease at 12 h PI. An increase in
      mean somatic cell counts was observed in the milk samples from 8 h PI onwards.
      Mild clinical signs were evoked by intramammary inoculation. Staphylococcus
      chromogenes could be isolated in tissue from all RMG. Histological examination of
      specimens of the RMG and lymph nodes of the goats showed an increased
      inflammatory response throughout the experiment with respect to control halves.
      In conclusion, the experimental inoculation of S. chromogenes in lactating goats
      is capable of eliciting an inflammatory response and capable of causing
      pathological changes. This research represents a preliminary study for a better
      knowledge of the mastitis pathogenesis caused by S. chromogenes.

PMID- 29360566
TI  - Black Zira essential oil: Chemical compositions and antimicrobial activity
      against the growth of some pathogenic strain causing infection.
AB  - The aim of this study was to perform chemical compositions and phytochemical
      analysis of Black Zira essential oil and other goal of this research was to
      investigate the antimicrobial effects of Black Zira essential oil against
      Enterobacter aerogenes, Pseudomonas aeruginosa, Escherichia coli, Shigella
      flexneri, Staphylococcus epidermidis, Streptococcus pyogenes and Candida
      albicans. Black Zira essential oil was extracted by hydrodistillation method
      using clevenger apparatus. Black Zira essential oil chemical composition was
      identified through gas chromatography/mass spectrometry. gamma-terpinene with a
      percentage of 24.8% was the major compound of Black Zira essential oil. The
      antimicrobial effect Black Zira essential oil was evaluated by several
      qualitative and quantitative methods (disk diffusion, well diffusion,
      microdilution broth, agar dilution and minimum bactericidal/fungicidal
      concentration). Phytochemical analysis Black Zira essential oil were appraised
      based on qualitative methods. Antioxidant activity (2,2-diphenyl-1-picrylhydrazyl
      and beta-carotene/linoleic acid inhibition) and total phenolic content (Folin
      Ciocalteu) were examined. The results of phytochemical analysis of Black Zira
      essential oil showed the existence of phenolic, flavonoids, saponins, alkaloids
      and tannins. The total phenolic content and antioxidant activity (reported as
      IC50) of Black Zira essential oil were equal to 120.50 +/- 0.50 mg GAE/g and
      11.55 +/- 0.25 MUg/ml, respectively. The MIC of the Black Zira essential oil
      ranged from 1 mg/ml to 8 mg/ml, while its MBC and MFC ranged from 1 mg/ml to 16
      mg/ml. The results presented that the longest and the shortest inhibition zone
      diameter at the concentration of 8 mg/ml pertained to C. albicans and E.
      aerogenes, respectively.

PMID- 29360567
TI  - Frequency of virulence factors in high biofilm formation blaKPC-2 producing
      Klebsiella pneumoniae strains from hospitals.
AB  - The aim of this study is to determine the frequency of virulence genes in high
      biofilm formation blaKPC-2 producing Klebsiella pneumoniae strains collected over
      a period of two years. A total of 43 non-repetitive high biofilm blaKPC-2
      producing isolates were screened from 429 strains. The MIC of carbapenems
      (imipenem and meropenem) ranged from 4 to 32 MUg/ml. The OD595 value of the
      biofilm ranged from 0.56 to 2.56. The K1, K2, K5, K20, K54, K57 genotypes, MLST
      and virulence factors, including entB, ybtS, mrkD, fimH, rmpA, allS, iutA, kfu,
      wcaG, aerobaction, fecIRA, shiF, magA and pagO gene, were determined by PCR. The
      results showed that, among the 43 isolates, 5 of 43 were K1 type, 25 of 43 were
      K2 type, 4 strains and 2 strains were K5 and K57 respectively. The MLST results
      showed that 23/43 strains were ST11, followed by ST433(4/43), ST107(4/43),
      ST690(4/43), ST304(2/43), ST2058(1/43), ST1(1/43), ST146(1/43), ST914(1/43),
      ST2636(1/43), ST2637(1/43). As to the virulence factors, all 43 strains carried
      entB, ybtS and mrkD gene, followed by fimH(38/43), rmpA(14/43), allS(34/43),
      iutA(27/43), kfu(25/43), wcaG(21/43), aerobaction(16/43), fecIRA(15/43),
      shiF(10/43), magA(5/43) and pagO(5/43). This study demonstrated that high
      frequency of virulence factors emerging in high biofim blaKPC-2 producing
      strains. It also suggested that we should continue to focus on the toxicity
      variation and it's high time to enhance clinical awareness to the infections
      causing by Klebsiella pneumoniae.

PMID- 29360568
TI  - Mitochondrial fragmentation in human macrophages attenuates palmitate-induced
      inflammatory responses.
AB  - Macrophages in adipose tissue contribute to inflammation and the development of
      insulin resistance in obesity. Exposure of macrophages to saturated fatty acids
      alters cell metabolism and activates pro-inflammatory signaling. How fatty acids
      influence macrophage mitochondrial dynamics is unclear. We investigated the
      mechanism of palmitate-induced mitochondrial fragmentation and its impact on
      inflammatory responses in primary human macrophages. Fatty acids, such as
      palmitate, caused mitochondrial fragmentation in human macrophages. Increased
      mitochondrial fragmentation was also observed in peritoneal macrophages from
      hyperlipidemic apolipoprotein E knockout mice. Fatty acid-induced mitochondrial
      fragmentation was independent of the fatty acid chain saturation and required
      dynamin-related protein 1 (DRP1). Mechanistically, mitochondrial fragmentation
      was regulated by incorporation of palmitate into mitochondrial phospholipids and
      their precursors. Palmitate-induced endoplasmic reticulum stress and loss of
      mitochondrial membrane potential did not contribute to mitochondrial
      fragmentation. Macrophages treated with palmitate maintained intact mitochondrial
      respiration and ATP levels. Pharmacological or genetic inhibition of DRP1
      enhanced palmitate-induced mitochondrial ROS production, c-Jun phosphorylation,
      and inflammatory cytokine expression. Our results indicate that mitochondrial
      fragmentation is a protective mechanism attenuating inflammatory responses
      induced by palmitate in human macrophages.

PMID- 29360569
TI  - Self-fitting shape memory polymer foam inducing bone regeneration: A rabbit
      femoral defect study.
AB  - Although tissue engineering has been attracted greatly for healing of critical
      sized bone defects, great efforts for improvement are still being made in
      scaffold design. In particular, bone regeneration would be enhanced if a scaffold
      precisely matches the contour of bone defects, especially if it could be
      implanted into the human body conveniently and safely. In this study,
      polyurethane/hydroxyapatite-based shape memory polymer (SMP) foam was fabricated
      as a scaffold substrate to facilitate bone regeneration. The minimally invasive
      delivery and the self-fitting behavior of the SMP foam were systematically
      evaluated to demonstrate its feasibility in the treatment of bone defects in
      vivo. Results showed that the SMP foam could be conveniently implanted into bone
      defects with a compact shape. Subsequently, it self-matched the boundary of bone
      defects upon shape-recovery activation in vivo. Micro-computed tomography
      determined that bone ingrowth initiated at the periphery of the SMP foam with a
      constant decrease towards the inside. Successful vascularization and bone
      remodeling were also demonstrated by histological analysis. Thus, our results
      indicate that the SMP foam demonstrated great potential for bone regeneration.

PMID- 29360570
TI  - The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom
      Cluster in Advanced Cancer.
AB  - CONTEXT: Symptom researchers have proposed a model of inflammatory cytokine
      activity and dysregulation in cancer to explain co-occurring symptoms including
      pain, fatigue, and sleep disturbance. OBJECTIVES: We tested the hypothesis that
      psychological stress accentuates inflammation and that stress and inflammation
      contribute to one's experience of the pain, fatigue, and sleep disturbance
      symptom cluster (symptom cluster severity, symptom cluster distress) and its
      impact (symptom cluster interference with daily life, quality of life). METHODS:
      We used baseline data from a symptom cluster management trial. Adult participants
      (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and
      sleep disturbance on enrollment. Before intervention, participants completed
      measures of demographics, perceived stress, symptom cluster severity, symptom
      cluster distress, symptom cluster interference with daily life, and quality of
      life and provided a blood sample for four inflammatory biomarkers (interleukin
      1beta, interleukin-6, tumor necrosis factor-alpha, and C-reactive protein).
      RESULTS: Stress was not directly related to any inflammatory biomarker. Stress
      and tumor necrosis factor-alpha were positively related to symptom cluster
      distress, although not symptom cluster severity. Tumor necrosis factor-alpha was
      indirectly related to symptom cluster interference with daily life, through its
      effect on symptom cluster distress. Stress was positively associated with symptom
      cluster interference with daily life and inversely with quality of life. Stress
      also had indirect effects on symptom cluster interference with daily life,
      through its effect on symptom cluster distress. CONCLUSION: The proposed
      inflammatory model of symptoms was partially supported. Investigators should test
      interventions that target stress as a contributing factor in co-occurring pain,
      fatigue, and sleep disturbance and explore other factors that may influence
      inflammatory biomarker levels within the context of an advanced cancer diagnosis
      and treatment.

PMID- 29360571
TI  - Communicating Caregivers' Challenges With Cancer Pain Management: An Analysis of
      Home Hospice Visits.
AB  - CONTEXT: Family caregivers (FCGs) of hospice cancer patients face significant
      challenges related to pain management. Addressing many of these challenges
      requires effective communication between FCGs and hospice nurses, yet little
      empirical evidence exists on the nature of communication about pain management
      between hospice nurses and FCGs. OBJECTIVES: We identified ways in which FCGs of
      hospice cancer patients communicated their pain management challenges to nurses
      during home visits and explored nurses' responses when pain management concerns
      were raised. METHODS: Using secondary data from audio recordings of hospice
      nurses' home visits, a deductive content analysis was conducted. We coded
      caregivers' pain management challenges and immediate nurses' responses to these
      challenges. RESULTS: From 63 hospice nurse visits, 101 statements describing
      caregivers' pain management challenges were identified. Thirty percent of these
      statements pertained to communication and teamwork issues. Twenty-seven percent
      concerned caregivers' medication skills and knowledge. In 52% of the cases,
      nurses responded to caregivers' pain management challenges with a validating
      statement. They provided information in 42% of the cases. Nurses did not address
      14% of the statements made by caregivers reflecting pain management challenges.
      CONCLUSION: To optimize hospice patients' comfort and reduce caregivers' anxiety
      and burden related to pain management, hospice nurses need to assess and address
      caregivers' pain management challenges during home visits. Communication and
      educational tools designed to reduce caregivers' barriers to pain management
      would likely improve clinical practice and both patient- and caregiver-related
      outcomes.

PMID- 29360572
TI  - Secreted frizzled related protein 4 (sFRP4) update: A brief review.
AB  - Secreted frizzled-related proteins control a multitude of biological phenomena
      throughout development and adult life in humans. In parallel, aberrant gene
      expression and abnormal secreted protein levels accompany a wide range of
      pathologies in humans. In this review, we provide a brief introduction to sFRP4,
      an update of the pathways it's involved, its various physiological actions that
      are reported to contribute to diseases, outlining the importance of its wider
      research and specific modulation by pharmacologic interventions. First recognized
      as a novel molecule that co-purified with a disparate protein, its identity was
      based on its sequence homology to the frizzled receptors. Once multiple members
      of the family were cloned, their genetic loci, tissue and subcellular
      distributions were located. Nucleotide and amino acid sequences were
      characterized and homology to different organisms was found to be present that
      helped elucidate their actions. Following subsequent experimental studies, they
      were found to be secreted proteins with an affinity to bind to the Wnt ligands,
      participating in different developmental and adult homeostatic pathways by the
      virtue of their regulatory function to the Wnt signal transduction system.
      Secreted frizzled related protein 4 has garnered considerable attention in the
      recent years following breakthrough discoveries implicating them in the
      pathogenesis of various diseases. Studies investigating them can provide
      information not only regarding their association with a disease but can also help
      use them as potential biomarkers and therapeutic targets.

PMID- 29360574
TI  - Investigating the effects of a penetrating vessel occlusion with a multi-scale
      microvasculature model of the human cerebral cortex.
AB  - The effect of the microvasculature on observed clinical parameters, such as
      cerebral blood flow, is poorly understood. This is partly due to the gap between
      the vessels that can be individually imaged in humans and the microvasculature,
      meaning that mathematical models are required to understand the role of the
      microvasculature. As a result, a multi-scale model based on morphological data
      was developed here that is able to model large regions of the human
      microvasculature. From this model, a clear layering of flow (and 1-dimensional
      depth profiles) was observed within a voxel, with the flow in the
      microvasculature being driven predominantly by the geometry of the penetrating
      vessels. It also appears that the pressure and flow are decoupled, both in
      healthy vasculatures and in those where occlusions have occurred, again due to
      the topology of the penetrating vessels shunting flow between them. Occlusion of
      a penetrating arteriole resulted in a very high degree of overlap of blood
      pressure drop with experimentally observed cell death. However, drops in blood
      flow were far more widespread, providing additional support for the theory that
      pericyte controlled regulation on the capillary scale likely plays a large part
      in the perfusion of tissue post-occlusion.

PMID- 29360573
TI  - Fluid intelligence and gross structural properties of the cerebral cortex in
      middle-aged and older adults: A multi-occasion longitudinal study.
AB  - According to Parieto-Frontal Integration Theory (P-FIT, Jung and Haier, 2007),
      individual differences in a circumscribed set of brain regions account for
      variations in general intelligence (g). The components of g, fluid (Gf) and
      crystallized (Gc) reasoning, exhibit distinct trajectories of age-related change.
      Because the brain also ages differentially, we hypothesized that age-related
      cognitive and neural changes would be coupled. In a sample of healthy middle-aged
      and older adults, we examined changes in Gf (operationalized by Cattell Culture
      Fair Test) and Gc (indexed by two vocabulary tests) as well as in structural
      properties of 19 brain regions. We fitted linear mixed models to the data
      collected on 73 healthy adults who participated in baseline assessment, with 43
      returning for at least one follow-up, and 16 of them contributing four repeated
      assessments over seven years. We observed age differences as well as longitudinal
      decline in Gf, contrasted to a lack of age differences and stability in Gc.
      Cortical thickness and cortical volume exhibited significant age differences and
      longitudinal declines, which were accelerated in P-FIT regions. Gf (but not Gc)
      was associated with cortical thickness, but no such relationship was found for
      cortical volume. Uniformity of cognitive change (lack of reliable individual
      differences) precluded examination of the coupling between cognitive and brain
      changes. Cortical shrinkage was greater in high-Gc individuals, whereas in
      participants with higher Gf cortical volume slower volume shrinkage was observed.

PMID- 29360575
TI  - A high-resolution computational localization method for transcranial magnetic
      stimulation mapping.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) is used for the mapping of
      brain motor functions. The complexity of the brain deters determining the exact
      localization of the stimulation site using simplified methods (e.g., the region
      below the center of the TMS coil) or conventional computational approaches.
      OBJECTIVE: This study aimed to present a high-precision localization method for a
      specific motor area by synthesizing computed non-uniform current distributions in
      the brain for multiple sessions of TMS. METHODS: Peritumoral mapping by TMS was
      conducted on patients who had intra-axial brain neoplasms located within or close
      to the motor speech area. The electric field induced by TMS was computed using
      realistic head models constructed from magnetic resonance images of patients. A
      post-processing method was implemented to determine a TMS hotspot by combining
      the computed electric fields for the coil orientations and positions that
      delivered high motor-evoked potentials during peritumoral mapping. The method was
      compared to the stimulation site localized via intraoperative direct brain
      stimulation and navigated TMS. RESULTS: Four main results were obtained: 1) the
      dependence of the computed hotspot area on the number of peritumoral measurements
      was evaluated; 2) the estimated localization of the hand motor area in eight non
      affected hemispheres was in good agreement with the position of a so-called "hand
      knob"; 3) the estimated hotspot areas were not sensitive to variations in tissue
      conductivity; and 4) the hand motor areas estimated by this proposal and direct
      electric stimulation (DES) were in good agreement in the ipsilateral hemisphere
      of four glioma patients. CONCLUSION(S): The TMS localization method was validated
      by well-known positions of the "hand-knob" in brains for the non-affected
      hemisphere, and by a hotspot localized via DES during awake craniotomy for the
      tumor-containing hemisphere.

PMID- 29360576
TI  - scribble (scrib) knockdown induces tumorigenesis by modulating Drp1-Parkin
      mediated mitochondrial dynamics in the wing imaginal tissues of Drosophila.
AB  - scrib loss of function is associated with various human-cancers. Most of the
      human-cancers have been characterized by mitochondrial dysfunction with elevated
      oxidative stress. However, the role of scrib to mitochondrial dysfunction in
      cancer has not been investigated earlier. Here, we have shown that scrib
      knockdown leads to mitochondrial depolarization, fragmentation and perinuclear
      clustering along with disruption of the redox homeostasis. Moreover, the scrib
      abrogated tumor showed the elevation of Drp-1 and reduced expression of Marf,
      which suggests enhanced mitochondrial-fission. Further, the reduced expression of
      Parkin and HtrA2 interpret defective mitophagy leading to clustering of
      fragmented mitochondria and apoptotic inhibition in scrib knockdown tumors. Also,
      Parkin immunostaining depicted its reduced expression and mislocalization in the
      tumor cells in comparison to wild type. Moreover, the genetic study revealed the
      epistatic interactions of parkin and scrib. Thus, for the first time our results
      suggested that scrib loss induced mitochondrial-dysfunction modulates cancer
      progression by altering the mitochondrial dynamics regulators.

PMID- 29360577
TI  - Test-retest reliability of the diagnosis of schizoaffective disorder in childhood
      and adolescence - A systematic review and meta-analysis.
AB  - OBJECTIVES: Reliability of schizoaffective disorder (SAD) diagnoses is low in
      adults but unclear in children and adolescents (CAD). We estimate the test-retest
      reliability of SAD and its key differential diagnoses (schizophrenia, bipolar
      disorder, and unipolar depression). METHODS: Systematic literature search of
      Medline, Embase, and PsycInfo for studies on test-retest reliability of SAD, in
      CAD. Cohen's kappa was extracted from studies. We performed meta-analysis for
      kappa, including subgroup and sensitivity analysis (PROSPERO protocol:
      CRD42013006713). RESULTS: Out of > 4000 records screened, seven studies were
      included. We estimated kappa values of 0.27 [95%-CI: 0.07 0.47] for SAD, 0.56
      [0.29; 0.83] for schizophrenia, 0.64 [0.55; 0.74] for bipolar disorder, and 0.66
      [0.52; 0.81] for unipolar depression. In 5/7 studies kappa of SAD was lower than
      that of schizophrenia; similar trends emerged for bipolar disorder (4/5) and
      unipolar depression (2/3). Estimates of positive agreement of SAD diagnoses
      supported these results. LIMITATIONS: The number of studies and patients included
      is low. CONCLUSIONS: The point-estimate of the test-retest reliability of
      schizoaffective disorder is only fair, and lower than that of its main
      differential diagnoses. All kappa values under study were lower in children and
      adolescents samples than those reported for adults. Clinically, schizoaffective
      disorder should be diagnosed in strict adherence to the operationalized criteria
      and ought to be re-evaluated regularly. Should larger studies confirm the
      insufficient reliability of schizoaffective disorder in children and adolescents,
      the clinical value of the diagnosis is highly doubtful.

PMID- 29360578
TI  - Motor impairment in patients with chronic neck pain: does the traumatic event
      play a significant role? A case-control study.
AB  - BACKGROUND CONTEXT: Motor impairment is a key sign in patients with traumatic
      (whiplash-associated disorder [WAD]) and non-traumatic (idiopathic neck pain
      [INP]) neck pain. PURPOSE: This study aimed to analyze differences in motor
      impairment between two patient groups and to assess the association between motor
      performance and self-reported symptoms. STUDY DESIGN: This is a case-control
      study. PATIENT SAMPLE: A total of 38 patients with chronic INP, 35 patients with
      chronic WAD, and 30 healthy pain-free controls were included in the study.
      OUTCOME MEASURES: Outcome measures used in this study were mobility ( degrees ),
      strength (N), repositioning accuracy ( degrees ), endurance (seconds), sway
      velocity (cm/s), sway area (cm2), and neuromuscular control. METHODS: Group
      differences of motor impairment, together with questionnaires to evaluate pain
      intensity, fear avoidance, pain catastrophizing, symptoms of central
      sensitization, and disability, were analyzed with analysis of covariance,
      including age as a covariate. RESULTS: Motor impairment was observed in both
      patient groups with a higher degree in patients with chronic WAD. These
      impairments were moderately linked to self-reported disability and were in most
      cases associated with pain, fear avoidance, and symptoms of central sensitization
      (|rho| ranging from 0.28 to 0.59). CONCLUSIONS: Motor impairment should be
      addressed when treating both groups of patients, keeping in mind the association
      with self-reported pain and disability, fear-avoidance, and central
      sensitization.

PMID- 29360579
TI  - L5 incidence: an important parameter for spinopelvic balance evaluation in high
      grade spondylolisthesis.
AB  - BACKGROUND: In high-grade spondylolisthesis (HGSPL), the pelvic incidence (PI) is
      not a reliable measurement because of doming of the sacrum. Measurement of L5
      incidence (L5I) was described as a tool to measure pelvic morphology in HGSPL and
      for surgical follow-up. OBJECTIVE: We aimed to evaluate L5I in HGSPL and its
      relationship to other spinopelvic parameters. STUDY DESIGN: A retrospective study
      of a cohort of 184 patients with HGSPL was carried out. METHODS: Whole spine
      radiographs were analyzed for PI, pelvic tilt (PT), sacral slope, lumbar lordosis
      (LL), L5I, L5 tilt (L5T), L5 slope, lumbosacral kyphosis, and slip percentage.
      Statistical analysis and correlation were made (Pearson correlation test; p<.05).
      In accordance to Cohen, statically significant correlation were considered strong
      if R>0.5, moderate if 0.3<R<0.5, and small if R<0.3. RESULTS: A total of 184
      cases were analyzed, with a female-to-male ratio of 2.35 and a mean age of 20.1
      years. Sacral doming was present in 73% of the cases. Mean L5I incidence was 65.2
      degrees  and strongly correlated to other sagittal parameters, especially PT
      (R=0.7), LL (R=0.7), L5T (R=0.77), and L5 slope (R=0.83). There was less but
      still strong correlation to Dubousset lumbosacral kyphosis (Dub-LSK) angle (R=
      0.63) and percentage of slippage (R=0.56). L5 tilt showed nearly perfect
      correlation to PT (R=0.95). Forty-four percent of the cases were balanced HGSPL,
      whereas 56% of the cases were unbalanced HGSPL. L5 incidence was found to be a
      good predictor of local imbalance with a cutoff of L5I=61. CONCLUSION: This paper
      describes L5I, which is a positional parameter in HGSPL. L5 incidence is a simple
      and reliable measure in the preoperative setting in HGSPL. Its correlation with
      spinal sagittal parameters (especially PT and LL) is strong and was found to be
      better than Dub-LSK. There is also a good correlation between L5I and HGSPL
      pelvic parameters (slip percentage and lumbosacral kyphosis). We recommend its
      use for evaluation of surgical correction and recommend the value of 60 degrees 
      as cutoff value to define spinopelvic balance in HGSPL.

PMID- 29360580
TI  - Models including plasma levels of sphingomyelins and phosphatidylcholines as
      diagnostic and prognostic biomarkers of endometrial cancer.
AB  - In endometrial cancer, biomarkers for preoperative identification of patients
      with low risk for disease progression would enable stratification according to
      the extent of surgery needed, and would avoid the complications that can be
      associated with radical surgery. A panel of proteins, amino acids, enzymes, and
      miRNA has been investigated as potential biomarkers for endometrial cancer. At
      the time of the manuscript submission targeted metabolomics/lipidomics approaches
      have not been applied to biomarker research in endometrial cancer. Using
      electrospray ionization-tandem mass spectrometry we quantified 163 metabolites in
      126 plasma samples (61 patients with endometrial cancer, 65 control patients).
      Three single phosphatidylcholines were identified with significantly decreased
      levels in patients with endometrial cancer. A diagnostic model was defined as the
      ratio between acylcarnitine C16 and phosphatidylcholine PCae C40:1, the ratio
      between proline and tyrosine, and the ratio between the two phosphatidylcholines
      PCaa C42:0 and PCae C44:5; which provided sensitivity of 85.25%, specificity of
      69.23%, and AUC of 0.837. Addition of smoking status further improved the
      constructed diagnostic model (AUC = 0.855). The presence of the major prognostic
      factors of deep myometrial invasion and lymphovascular invasion were also
      associated with altered metabolite concentrations. A prognostic model for deep
      myometrial invasion included the ratio between two hydroxysphingomyelins SMOH
      C14:1 and SMOH C24:1, and the ratio between two phosphatidylcholines PCaa C40:2
      and PCaa C42:6, which provided sensitivity of 81.25%, specificity of 86.36%, and
      AUC of 0.857. The model for lymphovascular invasion included the ratio between
      two phosphatidylcholines PCaa C34:4 and PCae C38:3, and the ratio between
      acylcarnitine C16:2 and phosphatidylcholine PCaa C38:1, which provided
      sensitivity of 88.89%, specificity of 84.31%, and AUC of 0.935.

PMID- 29360581
TI  - Cloning, expression and purification of kinase domains of cacao PR-1 receptor
      like kinases.
AB  - The PR-1 proteins (pathogenesis-related protein 1) are involved in plant defense
      mechanisms against various pathogens. The genome of cacao (Theobroma cacao)
      encodes 14 PR-1 proteins, named TcPR-1a to TcPR-1n. Two of them, TcPR-1f and TcPR
      1g, have a C-terminal expansion with high similarity to protein kinase domains,
      suggesting a receptor-like kinase (RLK) protein architecture. Moreover, TcPR-1g
      is highly expressed during cacao response to Witches' Broom Disease, caused by
      the fungus Moniliopthora perniciosa. Here we describe a structural genomics
      approach to clone, express and purify the kinase domains of TcPR-1f and TcPR-1g.
      Escherichia coli BL21(DE3)-R3 cells were used for protein expression and co
      expression of Lambda Protein Phosphatase was critical for successfully obtaining
      soluble recombinant protein. We expect that the ability to express and purify the
      kinase domains of TcPR-1f and TcPR-1g will further our understanding of the role
      these proteins play during cacao defense response.

PMID- 29360582
TI  - Keeping Practice Recommendations in Step with Advancing Knowledge.
AB  - This editorial comments on the updated molecular testing guideline for lung
      cancer patients.

PMID- 29360583
TI  - Is Psychiatric Depression a Presenting Neurologic Sign of Meningioma? A Critical
      Review of the Literature with Causative Etiology.
AB  - BACKGROUND: Benign meningiomas constitute 80%-90% of all meningiomas and
      represent the most common type of central nervous system tumor in adults. The
      vast majority of meningiomas are minimally symptomatic or asymptomatic early in
      their onset and thereby can often result in delayed diagnosis. Early diagnosis of
      meningioma is critical, as it can maximize treatment options and improve outcomes
      and survival. Although seizures and focal neurologic deficits are considered to
      be the most prevalent symptoms, depression also may be an important and
      significant sign. A subtle neurologic depression may be an even early presenting
      sign of meningioma and may precede more traditional presenting symptoms. METHODS:
      We performed a comprehensive literature review that analyzes the results of
      prospective studies and case reports on this topic. RESULTS: Our findings show
      evidence to suggest that depression may be correlated with meningioma
      presentation. Its prevalence is possibly increased with an anterior location of
      the tumor. CONCLUSIONS: For patients who exhibit nuances of depression without a
      history of psychiatric illness, an index of suspicion for meningioma may be
      warranted.

PMID- 29360584
TI  - Somatotrophic Adenoma in Children Younger than 14 Years: Clinical Features and
      Treatment of 22 Cases at a Large Pituitary Center.
AB  - OBJECTIVE: To investigate the clinical features of somatotrophic adenoma in
      children younger than 14 years and to evaluate the short-term and long-term
      outcomes of transsphenoidal surgery. METHODS: This single-center retrospective
      study included 22 patients with somatotrophic adenoma who were admitted to our
      institution between January 1997 and January 2017. The patients' demographics,
      hormone levels, imaging characteristics, surgical outcomes, and follow-up data
      were summarized. RESULTS: The average age of patients at diagnosis was 10.3
      years, and the average disease duration was 42.5 months. Growth acceleration was
      observed in 90.9% of patients. Mixed somatolactotrophic adenoma was identified in
      36.4% of patients. In total, 77.3% of tumors on imaging were macroadenomas or
      giant adenoma, and 50% were invasive. Twenty-one patients underwent tumor
      resection, and the remission rate after a single transsphenoidal surgery was 45%.
      Preoperative growth hormone levels (P = 0.017), growth hormone nadir (P = 0.003),
      and tumor size (P = 0.026) were the most likely influencing factors associated
      with the surgical remission rate. Postoperative cerebral spinal fluid leakage
      (15%) was the main complication of transsphenoidal surgery. During a median
      follow-up period of 42.5 months, 72.7% of the patients obtained remission after
      monotherapy or combined treatment, and no recurrence was observed. CONCLUSIONS:
      Somatotrophic adenomas in children younger than 14 years tend to be macroadenomas
      with a shorter disease duration than that observed in adults. Transsphenoidal
      surgery is safe and effective and could represent a preferred treatment option.
      The combination of surgery, medication, and radiation is recommended to achieve
      optimal long-term outcomes.

PMID- 29360585
TI  - Frailty and Health-Related Quality of Life Improvement Following Adult Spinal
      Deformity Surgery.
AB  - BACKGROUND: Although the Adult Spinal Deformity Frailty Index (ASD-FI) predicts
      major complications and prolonged hospital length of stay after adult spinal
      deformity surgery, the impact of frailty on postoperative changes in health
      related quality of life (HRQoL) is unknown. METHODS: Patients who underwent
      instrumented fusion of >=4 levels for adult spinal deformity with minimum 2-year
      follow-up were stratified by Adult Spinal Deformity Frailty Index score into 3
      groups: nonfrail, frail, and severely frail. Baseline and follow-up demographics,
      HRQoL measures, and radiographic parameters were analyzed. Primary outcome
      measures included proportion of patients who achieved substantial clinical
      benefit (SCB) in terms of Oswestry Disability Index, 36-Item Short Form Health
      Survey Physical Component Summary, and numeric back and leg pain scores. RESULTS:
      Inclusion criteria were met by 332 patients (135 nonfrail, 175 frail, 22 severely
      frail). Frail and severely frail patients were older and had more comorbidities,
      worse baseline HRQoL and pain scores, and worse radiographic deformity than
      nonfrail patients (P < 0.05). At 2-year follow-up, all outcome scores were worse
      in frail and severely frail patients compared with nonfrail patients. Frail
      patients improved more than nonfrail patients and were more likely to reach SCB
      for Oswestry Disability Index (43.7% vs. 29.3%; P = 0.025), 36-Item Short Form
      Health Survey Physical Component Summary (56.9% vs. 51.2%; P = 0.03), and leg
      pain (45.8% vs. 23.0%; P = 0.03) scores, but not back pain (57.5% vs. 63.4%; P =
      0.045) score. CONCLUSIONS: Despite higher risk stratification and worse baseline
      HRQoL, frail patients were more likely to reach SCB for most HRQoL measures
      compared with nonfrail patients. Severely frail patients were the least likely to
      reach SCB for most HRQoL measures.

PMID- 29360586
TI  - Intracranial Vessel Wall Imaging with Magnetic Resonance Imaging: Current
      Techniques and Applications.
AB  - Vessel wall magnetic resonance imaging (VW-MRI) is a modern imaging technique
      with expanding applications in the characterization of intracranial vessel wall
      pathology. VW-MRI provides added diagnostic capacity compared with conventional
      luminal imaging methods. This review explores the principles of VW-MRI and
      typical imaging features of various vessel wall pathologies, such as
      atherosclerosis, dissection, and vasculitis. Radiologists should be familiar with
      this important imaging technique, given its increasing use and future relevance
      to everyday practice.

PMID- 29360587
TI  - Occipital Artery and Its Segments in Vertebral Artery Revascularization Surgery:
      A Microsurgical Anatomic Study.
AB  - OBJECTIVE: To study the microsurgical anatomy of the occipital artery (OA) to
      determine the optimal segment for use as a conduit in revascularization bypass
      surgery. METHODS: Twelve sides of 6 cadaveric heads that had been injected with
      colored silicone were exposed using C-shaped postauricular incision. The OA was
      dissected from its point of origin to the proximal part of the distal segment.
      For each segment, the diameters and length were measured, and its branches and
      proximity to the recipient vessel (V3) were examined. RESULTS: The mean diameters
      were 2.6 mm at the digastric segment, 2.04 mm at the point where it exits the
      mastoid sulcus, 2.0 mm, at the point just before the last descending muscular
      branch, and 1.8 mm and 1.5 mm after the branch and attached to the superior
      nuchal line, respectively. The length of the OA from the point where it exits the
      mastoid sulcus to the point at which it revealed the last descending muscular
      branch was 53 mm, and the distance of this section to the V3 was 31 mm.
      CONCLUSIONS: In pathologies necessitating vertebral artery revascularization
      surgery, it is possible to easily mobilize the OA with a C-shaped postauricular
      incision in the lateral suboccipital region. To reach a more appropriate segment
      in terms of diameter, length, and easy anastomosis, V3 sulcal and OA suboccipital
      segments are more suitable. Thus, if bypass surgery is indicated in cases of
      vertebrobasilar ischemia, the suboccipital segment of the OA may be an ideal
      choice and considered as an artery that can be used in "SOS" conditions.

PMID- 29360588
TI  - Motor Cortex Reorganization in Patients with Glioma Assessed by Repeated
      Navigated Transcranial Magnetic Stimulation-A Longitudinal Study.
AB  - OBJECTIVE: Evidence for cerebral reorganization after resection of low-grade
      glioma has mainly been obtained by serial intraoperative cerebral mapping.
      Noninvasively collected data on cortical plasticity in tumor patients over a
      surgery-free period are still scarce. The present study therefore aimed at
      evaluating motor cortex reorganization by navigated transcranial magnetic
      stimulation (nTMS) in patients after perirolandic glioma surgery. METHODS: nTMS
      was performed preoperatively and postoperatively in 20 patients, separated by
      26.1 +/- 24.8 months. Further nTMS mapping was conducted in 14 patients,
      resulting in a total follow-up period of 46.3 +/- 25.4 months. Centers of gravity
      (CoGs) were calculated for every muscle representation area, and Euclidian
      distances between CoGs over time were defined. Results were compared with data
      from 12 healthy individuals, who underwent motor cortex mapping by nTMS in 2
      sessions. RESULTS: Preoperatively and postoperatively pooled CoGs from the area
      of the dominant abductor pollicis brevis muscle and of the nondominant leg area
      differed significantly compared with healthy individuals (P < 0.05). Most
      remarkably, during the ensuing follow-up period, a reorganization of all
      representation areas was observed in 3 patients, and a significant shift of hand
      representation areas was identified in further 3 patients. Complete functional
      recovery of postoperative motor deficits was exclusively associated with cortical
      reorganization. CONCLUSIONS: Despite the low potential of remodeling within the
      somatosensory region, long-term reorganization of cortical motor function can be
      observed. nTMS is best suited for a noninvasive evaluation of this
      reorganization.

PMID- 29360589
TI  - Virtual Reality Glasses and "Eye-Hands Blind Technique" for Microsurgical
      Training in Neurosurgery.
AB  - OBJECTIVE: Microsurgical skills and eye-hand coordination need continuous
      training to be developed and refined. However, well-equipped microsurgical
      laboratories are not so widespread as their setup is expensive. Herein, we
      present a novel microsurgical training system that requires a high-resolution
      personal computer screen, smartphones, and virtual reality glasses. METHODS: A
      smartphone placed on a holder at a height of about 15-20 cm from the surgical
      target field is used as the webcam of the computer. A specific software is used
      to duplicate the video camera image. The video may be transferred from the
      computer to another smartphone, which may be connected to virtual reality
      glasses. RESULTS: Using the previously described training model, we progressively
      performed more and more complex microsurgical exercises. It did not take long to
      set up our system, thus saving time for the training sessions. CONCLUSION: Our
      proposed training model may represent an affordable and efficient system to
      improve eye-hand coordination and dexterity in using not only the operating
      microscope but also endoscopes and exoscopes.

PMID- 29360590
TI  - Genetic Variations of the COL4A1 Gene and Intracerebral Hemorrhage Risk: A Case
      Control Study in a Chinese Han Population.
AB  - OBJECTIVE: To investigate the association between single nucleotide polymorphisms
      or haplotypes of the COL4A1 gene and the risk of intracerebral hemorrhage (ICH).
      METHODS: We conducted a case-control study that included 181 patients from the
      Chinese Han population with hypertensive ICH and 197 hypertension patients
      without ICH. Genomic DNA was extracted by DNA extraction kit, and the 6 single
      nucleotide polymorphism genotypes of the COL4A1 gene were detected with a
      MassARRAY Analyzer. Unphased 3.1.4 and SPSS 19.0 were used to analyze the
      association between alleles, genotypes, and haplotypes of the COL4A1 gene and the
      risk of ICH. RESULTS: Compared with the control group, patients in the ICH group
      were significantly younger. There were no differences in gender, diabetes,
      hyperlipidemia, current smoking, and alcohol consumption between the 2 groups.
      Our association analysis showed that the rs3742207 A, rs11069830 A, and rs679505
      A alleles were association factors of the risks of ICH; rs11069830 AA, rs544012
      AC, and rs679505 AA genotypes were association factors of the risk of ICH; AA
      haplotype (rs3742207-rs11069830) was an association factor of the risk of ICH.
      After adjusting age and gender by multivariate logistic regression, the rs544012
      AC and rs679505 AA genotypes were independently associated with the risk of ICH.
      CONCLUSIONS: Our study showed that the rs544012 AC and rs679505 AA genotypes were
      independently associated with the risk of ICH in the Chinese Han population and
      that the AA haplotype (rs3742207-rs11069830) in the COL4A1 gene may be related to
      the risk of ICH in the Chinese Han population; these conclusions need further
      confirmation in future studies with larger samples.

PMID- 29360591
TI  - Current Perspectives in Imaging Modalities for the Assessment of Unruptured
      Intracranial Aneurysms: A Comparative Analysis and Review.
AB  - BACKGROUND: Intracranial aneurysms (IAs) are pathologic dilatations of cerebral
      arteries. This systematic review summarizes and compares imaging techniques for
      assessing unruptured IAs (UIAs). This review also addresses their uses in
      different scopes of practice. Pathophysiologic mechanisms are reviewed to better
      understand the clinical usefulness of each imaging modality. METHODS: A
      literature review was performed using PubMed with these search terms:
      "intracranial aneurysm," "cerebral aneurysm," "magnetic resonance angiography
      (MRA)," computed tomography angiography (CTA)," "catheter angiography," "digital
      subtraction angiography," "molecular imaging," "ferumoxytol," and
      "myeloperoxidase". Only studies in English were cited. RESULTS: Since the
      development and improvement of noninvasive diagnostic imaging (computed
      tomography angiography and magnetic resonance angiography), many prospective
      studies and meta-analyses have compared these tests with gold standard digital
      subtraction angiography (DSA). Although computed tomography angiography and
      magnetic resonance angiography have lower detection rates for UIAs, they are
      vital in the treatment and follow-up of UIAs. The reduction in ionizing radiation
      and lack of endovascular instrumentation with these modalities provide benefits
      compared with DSA. Novel molecular imaging techniques to detect inflammation
      within the aneurysmal wall with the goal of stratifying risk based on level of
      inflammation are under investigation. CONCLUSIONS: DSA remains the gold standard
      for preoperative planning and follow-up for patients with IA. Newer imaging
      modalities such as ferumoxytol-enhanced magnetic resonance imaging are emerging
      techniques that provide critical in vivo information about the inflammatory
      milieu within aneurysm walls. With further study, these techniques may provide
      aneurysm rupture risk and prediction models for individualized patient care.

PMID- 29360592
TI  - Trajectories of adherence to home-based exercise programs among people with knee
      osteoarthritis.
AB  - OBJECTIVE: To investigate the presence of different trajectories of self-reported
      adherence to home exercise programs among people with knee osteoarthritis (OA),
      and to compare baseline characteristics across identified groups. DESIGN: Pooled
      analysis of data from three randomised controlled trials involving exercise
      interventions for people aged >=50 years with clinical knee OA (n = 341).
      Exercise adherence was self-reported on an 11-point numerical rating scale (NRS;
      0 = not at all-10 = completely as instructed). Latent class growth analysis was
      used to identify distinct trajectories of adherence, at intervals from 12 to 78
      weeks from baseline. Baseline characteristics of these groups were compared using
      chi-squared tests, one-way analysis of variance (ANOVA) and Kruskal Wallis tests
      where appropriate. RESULTS: Three distinct adherence trajectories were
      identified: a "Rapidly declining adherence" group (n = 157, 47.4%) whose
      adherence was 7.7 +/- 1.6 (/10) at 12 weeks, declined to 4.2 +/- 2.2 by 22 weeks
      and remained low thereafter; a "Gradually declining adherence" group (n = 153,
      45.1%) whose adherence declined from 8.5 +/- 1.5 to 7.8 +/- 1.5 over the same
      period, and continued to decline slowly, and a "Low adherence" group (n = 21,
      6.3%) whose adherence was 2.2 +/- 1.4 at 12 weeks and remained low. At baseline
      the "Rapidly declining adherence" group reported significantly lower Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (mean
      difference (95% Confidence Interval (CI)) -0.8 (-1.4, -0.2)) and better WOMAC
      function compared to the "Gradually declining adherence" group (-3.1 (-5.2, 
      1.1)). CONCLUSION: Three trajectories of self-reported adherence to home
      exercises were found among people with knee OA. Findings highlight the need for
      close monitoring of adherence from initiation of a home exercise program in order
      to identify and intervene when low or rapidly declining adherence is identified.

PMID- 29360593
TI  - The embryonic developmental effect of sedaxane on zebrafish (Danio rerio).
AB  - The succinate dehydrogenase inhibitor (SDHI) fungicides have been extensively
      used in agriculture, and some of their potential ecological risks to aquatic
      organisms have been demonstrated recently. Sedaxane (SDX) is a broad spectrum
      SDHI fungicide. Despite being extensively used in environment, little is known
      about its potential developmental effect in zebrafish embryo. This study examined
      the effects of which SDX triggered in zebrafish through embryonic development
      assessments. Results show that SDX induced mortality, hatch delay and failure in
      zebrafish embryos, which were concentration dependent. In addition, several
      developmental abnormalities were observed at 2 mg/L and higher concentrations,
      including edema, microcephaly, body deformation, and swim bladder not fully
      inflated. SDX exposure influenced reactive oxygen species, malondialdehyde,
      peroxidase, glutathione S-transferase, superoxide dismutase and glutathione in
      live larvae, which indicated that oxidative stress was caused in zebrafish.
      Furthermore, SDX induced decrease of succinate dehydrogenase activity in
      zebrafish larvae. These results provide toxicological data of SDX on developing
      zebrafish embryo, which could be help for further understanding the potential
      risk on the environment.

PMID- 29360594
TI  - Bioaccumulation of heavy metals in maricultured fish, Lates calcarifer
      (Barramudi), Lutjanus campechanus (red snapper) and Lutjanus griseus (grey
      snapper).
AB  - Mariculture fish contains a rich source of protein, but some species may
      bioaccumulate high levels of heavy metals, making them unsafe for consumption.
      This study aims to identify heavy metal concentration in Lates calcarifer
      (Barramudi), Lutjanus campechanus (Red snapper) and Lutjanus griseus (Grey
      snapper). Three species of mariculture fish, namely, L. calcarifer, L.
      campechanus and L. griseus were collected for analyses of heavy metals. The
      concentration of heavy metal (As, Cd, Cu, Cr, Fe, Pb, Mn, Ni, Se, and Zn) was
      determined using inductive coupled plasma mass spectrometry (ICP-MS). The
      distribution of heavy metals mean concentration in muscle is Zn > Fe > As > Se >
      Cr > Cu > Mn > Pb > Ni > Cd for L. calcarifer, Fe > Zn > Cr > As > Ni > Mn > Se >
      Cu > Pb > Cd for L. campechanus and Fe > Zn > Cr > Ni > Se > Cu > As > Mn > Pb >
      Cd for L. griseus. Among all of the species under investigation, the highest
      concentration of Fe was found in the muscle tissue of L. campechanus (19.985 +/-
      1.773 mg kg-1) and liver tissue of L. griseus (58.248 +/- 8.736 mg kg-1).
      Meanwhile, L. calcarifer has the lowest concentration of Cd in both muscle (0.007
      +/- 0.004 mg kg-1) and liver tissue (0.027 +/- 0.016 mg kg-1). The heavy metal
      concentration in muscle tissue is below the permissible limit guidelines
      stipulated by the Food & Agriculture Organization, 1983 and Malaysia Food Act,
      1983. The concentration of heavy metals varies significantly among fish species
      and tissues. L. campechanus was found to have a higher ability to accumulate
      heavy metals as compared to the other two species (p < .00). Among all the
      studied fish, liver tissue has a higher concentration of heavy metals compared to
      muscle tissue (p < .05). The findings from this study can serve as baseline
      information for future monitoring and risk assessment studies. Periodic
      monitoring of heavy metal concentration in mariculture fish must be performed to
      prevent acute and chronic food intoxication.

PMID- 29360595
TI  - Element mobilization and immobilization from carbonate rocks between CO2 storage
      reservoirs and the overlying aquifers during a potential CO2 leakage.
AB  - Despite the numerous studies on changes within the reservoir following CO2
      injection and the effects of CO2 release into overlying aquifers, little or no
      literature is available on the effect of CO2 release on rock between the storage
      reservoirs and subsurface. This is important, because the interactions that occur
      in this zone between the CO2 storage reservoir and the subsurface may have a
      significant impact on risk analysis for CO2 storage projects. To address this
      knowledge gap, relevant rock materials, temperatures and pressures were used to
      study mineralogical and elemental changes in this intermediate zone. After rocks
      reacted with CO2-acidified 0.01 M NaCl, liquid analysis showed an increase of
      major elements (e.g., Ca and Mg) and variable concentrations of potential
      contaminants (e.g., Sr and Ba); lower aqueous concentrations of these elements
      were observed in N2 control experiments, likely due to differences in pH between
      the CO2 and N2 experiments. In experiments with As/Cd and/or organic spikes,
      representing potential contaminants in the CO2 plume originating in the storage
      reservoir, most or all of these contaminants were removed from the aqueous phase.
      SEM and Mossbauer spectroscopy results showed the formation of new minerals and
      Fe oxides in some CO2-reacted samples, indicating potential for contaminant
      removal through mineral incorporation or adsorption onto Fe oxides. These
      experiments show the interactions between the CO2-laden plume and the rock
      between storage reservoirs and overlying aquifers have the potential to affect
      the level of risk to overlying groundwater, and should be considered during site
      selection and risk evaluation.

PMID- 29360596
TI  - High-resolution insight into the competitive adsorption of heavy metals on
      natural sediment by site energy distribution.
AB  - Investigating competitive adsorption on river/lake sediments is valuable for
      understanding the fate and transport of heavy metals. Most studies have studied
      the adsorption isotherms of competitive heavy metals, which mainly comparing the
      adsorption information on the same concentration. However, intrinsically, the
      concentration of each heavy metal on competitive adsorption sites is different,
      while the adsorption energy is identical. Thus, this paper introduced the site
      energy distribution theory to increase insight into the competitive adsorption of
      heavy metals (Cu, Cd and Zn). The site energy distributions of each metal with
      and without other coexisting heavy metals were obtained. It illustrated that site
      energy distributions provide much more information than adsorption isotherms
      through screening of the full energy range. The results showed the superior heavy
      metal in each site energy area and the influence of competitive metals on the
      site energy distribution of target heavy metal. Site energy distributions can
      further help in determining the competitive sites and ratios of coexisting
      metals. In particular, in the high-energy area, which has great environmental
      significance, the ratios of heavy metals in the competitive adsorption sites
      obtained for various competitive systems were as follows: slightly more than 3:1
      (Cu-Cd), slightly less than 3:1 (Cu-Zn), slightly more than 1:1 (Cd-Zn), and
      nearly 7:2:2 (Cu-Cd-Zn). The results from this study are helpful to deeply
      understand competitive adsorption of heavy metals (Cu, Cd, Zn) on sediment.
      Therefore, this study was effective in presenting a general pattern for future
      reference in competitive adsorption studies on sediments.

PMID- 29360597
TI  - Model-based assessment of estrogen removal by nitrifying activated sludge.
AB  - Complete removal of estrogens such as estrone (E1), estradiol (E2), estriol (E3)
      and ethinylestradiol (EE2) in wastewater treatment is essential since their
      release and accumulation in natural water bodies are giving rise to environment
      and health issues. To improve our understanding towards the estrogen
      bioremediation process, a mathematical model was proposed for describing estrogen
      removal by nitrifying activated sludge. Four pathways were involved in the
      developed model: i) biosorption by activated sludge flocs; ii) cometabolic
      biodegradation linked to ammonia oxidizing bacteria (AOB) growth; iii) non-growth
      biodegradation by AOB; and iv) biodegradation by heterotrophic bacteria (HB). The
      degradation kinetics was implemented into activated sludge model (ASM) framework
      with consideration of interactions between substrate update and microorganism
      growth as well as endogenous respiration. The model was calibrated and validated
      by fitting model predictions against two sets of batch experimental data under
      different conditions. The model could satisfactorily capture all the dynamics of
      nitrogen, organic matters (COD), and estrogens. Modeling results suggest that for
      E1, E2 and EE2, AOB-linked biodegradation is dominant over biodegradation by HB
      at all investigated COD dosing levels. However, for E3, the increase of COD
      dosage triggers a shift of dominant pathway from AOB biodegradation to HB
      biodegradation. Adsorption becomes the main contributor to estrogen removal at
      high biomass concentrations.

PMID- 29360598
TI  - Adsorption by and artificial release of zinc and lead from porous concrete for
      recycling of adsorbed zinc and lead and of porous concrete to reduce urban non
      point heavy metal runoff.
AB  - This report describes the use of porous concrete at the bottom of a sewage trap
      to prevent runoff of non-point heavy metals into receiving waters, and,
      secondarily, to reduce total runoff volume during heavy rains in urbanized areas
      while simultaneously increasing the recharge volume of heavy-metal-free water
      into underground aquifers. This idea has the advantage of preventing clogging,
      which is fundamentally very important when using pervious materials. During
      actual field experiments, two important parameters were identified: maximum
      adsorption weight of lead and zinc by the volume of porous concrete, and heavy
      metal recovery rate by artificial acidification after adsorption. To understand
      the effect of ambient heavy metal concentration, a simple mixing system was used
      to adjust the concentrations of lead and zinc solutions. The concrete blocks used
      had been prepared for a previous study by Harada & Komuro (2010). The results
      showed that maximum adsorption depended on the ambient concentration, expressed
      as the linear isothermal theory, and that recovery depended on the final pH value
      (0.5 or 0.0). The dependence on pH is very important for recycling the porous
      concrete. A pH of 0.5 is important for recycling both heavy metals, especially
      zinc, (8.0-22.1% of lead and 42-74% of zinc) and porous concrete because porous
      concrete has not been heavily damaged by acid. However, at a pH of 0.0, the heavy
      metals could be recovered: 30-60% of the lead and 75-125% of the zinc. At a
      higher pH, such as 2.0, no release of heavy metals occurred, indicating the
      safety to the environment of using porous concrete, because the lowest recorded
      pH of rainfall in Japan is. 4.0.

PMID- 29360599
TI  - An Empirically Derived Pediatric Cardiac Inotrope Score Associated With Pediatric
      Heart Surgery.
AB  - We aimed to empirically derive an inotrope score to predict real-time outcomes
      using the doses of inotropes after pediatric cardiac surgery. The outcomes
      evaluated included in-hospital mortality, prolonged hospital length of stay, and
      composite poor outcome (mortality or prolonged hospital length of stay). The
      study population included patients <18 years of age undergoing heart operations
      (with or without cardiopulmonary bypass) of varying complexity. To create this
      novel pediatric cardiac inotrope score (PCIS), we collected the data on the
      highest doses of 4 commonly used inotropes (epinephrine, norepinephrine,
      dopamine, and milrinone) in the first 24 hours after heart operation. We employed
      a hierarchical framework by representing discrete probability models with
      continuous latent variables that depended on the dosage of drugs for a particular
      patient. We used Bayesian conditional probit regression to model the effects of
      the inotropes on the mean of the latent variables. We then used Markov chain
      Monte Carlo simulations for simulating posterior samples to create a score
      function for each of the study outcomes. The training dataset utilized 1030
      patients to make the scientific model. An online calculator for the tool can be
      accessed at https://soipredictiontool.shinyapps.io/InotropeScoreApp. The newly
      proposed empiric PCIS demonstrated a high degree of discrimination for predicting
      study outcomes in children undergoing heart operations. The newly proposed
      empiric PCIS provides a novel measure to predict real-time outcomes using the
      doses of inotropes among children undergoing heart operations of varying
      complexity.

PMID- 29360600
TI  - Lowering of blood pressure after nitrate-rich vegetable consumption is abolished
      with the co-ingestion of thiocyanate-rich vegetables in healthy normotensive
      males.
AB  - A diet rich in vegetables is known to provide cardioprotection. However, it is
      unclear how the consumption of different vegetables might interact to influence
      vascular health. This study tested the hypothesis that nitrate-rich vegetable
      consumption would lower systolic blood pressure but that this effect would be
      abolished when nitrate-rich and thiocyanate-rich vegetables are co-ingested. On
      four separate occasions, and in a randomized cross-over design, eleven healthy
      males reported to the laboratory and consumed a 750 mL vegetable smoothie that
      was either: low in nitrate (~0.3 mmol) and thiocyanate (~5 MUmol), low in nitrate
      and high in thiocyanate (~72 MUmol), high in nitrate (~4 mmol) and low in
      thiocyanate and high in nitrate and thiocyanate. Blood pressure as well as plasma
      and salivary [thiocyanate], [nitrate] and [nitrite] were assessed before and 3 h
      after smoothie consumption. Plasma [nitrate] and [nitrite] and salivary [nitrate]
      were not different after consuming the two high-nitrate smoothies, but salivary
      [nitrite] was higher after consuming the high-nitrate low-thiocyanate smoothie
      (1183 +/- 625 MUM) compared to the high-nitrate high-thiocyanate smoothie (941 +/
      532 MUM; P < .001). Systolic blood pressure was only lowered after consuming the
      high-nitrate low-thiocyanate smoothie (-3 +/- 5 mmHg; P < .05). The acute
      consumption of vegetables high in nitrate and low in thiocyanate lowered systolic
      blood pressure. However, when the same dose of nitrate-rich vegetables was co
      ingested with thiocyanate-rich vegetables the increase in salivary [nitrite] was
      smaller and systolic blood pressure was not lowered. These findings might have
      implications for optimising dietary guidelines aimed at improving cardiovascular
      health.

PMID- 29360601
TI  - Farmers' knowledge and opinions towards bollgard II(r) implementation in cotton
      production in western Burkina Faso.
AB  - In 2008, the commercial cultivation of Genetically Modified (GM) cotton (Bollgard
      II(r)) started in Burkina Faso. The adoption rate increased rapidly in subsequent
      years to reach around 70% in 2014. Although some criticisms were raised
      concerning the suitability of the technology for the farming system in Burkina
      Faso, the introduction of transgenic cotton in the country was generally regarded
      as a great success. Despite this, during the 2016-2017 agricultural campaign, the
      government of Burkina Faso decided to suspend the cultivation of Bollgard II(r).
      In this context, this paper investigates farmers' knowledge, perceptions,
      opinions and attitudes towards Bollgard II(r) as well as their views on the
      recent decision to suspend its cultivation. Data was collected from 324 cotton
      farmers, both growers of conventional and Bollgard II(r). The results showed that
      the farmers surveyed had a poor knowledge concerning the core concepts of
      biotechnology and Bollgard II(r) in particular. Moreover, the regulatory
      oversight of the implementation of the technology was found insufficient, as
      illustrated by the lack of compliance with prescriptions concerning refuge areas
      and pesticide treatments. Nevertheless, overall, the farmers interviewed had a
      slightly positive opinion about the effects on yield, income and their wellbeing.
      In particular the reduction in pesticide treatments was perceived very positively
      by all respondents. Although the study finds that the majority of farmers
      disagreed with the recent suspension of Bt cotton cultivation by the government,
      it also makes clear that a thorough debate on the technology and its
      implementation is necessary.

PMID- 29360602
TI  - Determining Y-STR mutation rates in deep-routing genealogies: Identification of
      haplogroup differences.
AB  - Knowledge of Y-chromosomal short tandem repeat (Y-STR) mutation rates is
      essential to determine the most recent common ancestor (MRCA) in familial
      searching or genealogy research. Up to now, locus-specific mutation rates have
      been extensively examined especially for commercially available forensic Y-STRs,
      while haplogroup specific mutation rates have not yet been investigated in
      detail. Through 450 patrilineally related namesakes distributed over 212 deep
      rooting genealogies, the individual mutation rates of 42 Y-STR loci were
      determined, including 27 forensic Y-STR loci from the Yfiler(r) Plus kit and 15
      additional Y-STR loci (DYS388, DYS426, DYS442, DYS447, DYS454, DYS455, DYS459a/b,
      DYS549, DYS607, DYS643, DYS724a/b and YCAIIa/b). At least 726 mutations were
      observed over 148,596 meiosis and individual Y-STR mutation rates varied from
      2.83 * 10-4 to 1.86 * 10-2. The mutation rate was significantly correlated with
      the average allele size, the complexity of the repeat motif sequence and the age
      of the father. Significant differences in average Y-STR mutations rates were
      observed when haplogroup 'I & J' (4.03 * 10-3 mutations/generation) was compared
      to 'R1b' (5.35 * 10-3 mutations/generation) and to the overall mutation rate
      (5.03 * 10-3 mutations/generation). A difference in allele size distribution was
      identified as the only cause for these haplogroup specific mutation rates. The
      haplogroup specific mutation rates were also present within the commercially
      available Y-STR kits (Yfiler(r), PowerPlex(r) Y23 System and Yfiler(r) Plus).
      This observation has consequences for applications where an average Y-STR
      mutation rate is used, e.g. tMRCA estimations in familial searching and genealogy
      research.

PMID- 29360603
TI  - Hybrid organic-inorganic anion-exchange pore-filled membranes for the recovery of
      nitric acid from highly acidic aqueous waste streams.
AB  - Recycling of acid from aqueous waste streams is highly important not only from
      the environmental point of view but also for developing the sustainable
      technology. One of the effective ways to recover acid from aqueous waste streams
      is the anion-exchange membrane based diffusion-dialysis. The work presents the
      synthesis and characterization of anion-exchange pore-filled membranes for the
      objective of recovery of high concentration of acid by diffusion dialysis. The
      membranes were prepared by anchoring the guest organic-inorganic anionic gel in
      the pores of the host poly(propylene) membrane by in situ UV-initiator induced
      polymerization of the appropriate monomers along with cross-linker. The removal
      of nitric acid in the presence of different representative monovalent, divalent
      and trivalent nitrates and the leakage of these ions through anion exchange
      membrane have been studied by DD technique for optimizing the chemical
      composition of the membrane. The nitric acid permeation rate of the membrane with
      the optimized composition has been found to be considerably faster than the
      commercial Selemion membrane without sacrificing salt leakage. The performance of
      the optimized pore-filled anion exchange membranes has been found to be
      independent of the acid concentration, nature of the anion and substrate and has
      been observed to be solely dependent on the guest inorganic-organic hybrid
      anionic gel component. The membranes have been found to be stable and reusable
      for the acid recovery. Removal of nitric acid as high as 90% from the simulated
      high level nuclear waste with the optimized grafted pore-filled membrane has been
      achieved with negligible salt transport.

PMID- 29360604
TI  - Rechallenge with BRAF-directed treatment in metastatic melanoma: A multi
      institutional retrospective study.
AB  - BACKGROUND: Most metastatic melanoma patients treated with BRAF inhibitors
      (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with
      acquired resistance due to genetic changes, epigenetic mechanisms that could be
      reversed after BRAFi discontinuation have been described. The purpose of this
      study was to analyse retrospectively outcomes for patients retreated with BRAF
      directed therapy. PATIENTS AND METHODS: One hundred sixteen metastatic melanoma
      patients who received BRAFi-based therapy and, after a break, were rechallenged
      with BRAFi +/- MEKi at 14 centres in Europe, US and Australia were studied,
      respectively. Response rate (RR), overall survival (OS) and progression-free
      survival (PFS) from the start of retreatment were calculated. RESULTS: The median
      duration of treatment was 9.4 months for first BRAFi +/- MEKi treatment and 7.7
      months for the subsequent treatment (immunotherapy 72%, other 17%, drug holiday
      11%) after BRAFi discontinuation. Brain metastases were present in 51 (44%)
      patients at BRAFi retreatment. The RR to rechallenge with BRAFi +/- MEKi was
      43.3%: complete response (CR) 2.6%, partial response (PR) 40.7%, stable disease
      (SD) 24.8% and progressive disease 31.9%, 3 missing. Of 83 patients who
      previously discontinued BRAFi due to disease progression, 31 (37.3%) responded
      (30 PR and 1 CR) to retreatment. The median OS from retreatment was 9.8 months,
      and PFS was 5 months. Independent prognostic factors for survival at rechallenge
      included number of metastatic sites (hazard ratio [HR] = 1.32 for each additional
      organ with metastases, P < .001), lactic dehydrogenase (HR = 1.37 for each
      multiple of the upper normal limit, P < .001), while rechallenge with combination
      BRAFi + MEKi conferred a better OS versus BRAFi alone (HR = 0.5, P = .006).
      CONCLUSION: Rechallenge with BRAFi +/- MEKi results in a clinically meaningful
      benefit and should be considered for selected patients.

PMID- 29360605
TI  - Kinetics and nadir of responses to immune checkpoint blockade by anti-PD1 in
      patients with classical Hodgkin lymphoma.
AB  - BACKGROUND: We aimed to define the depth and time of maximal anti-tumour response
      to programmed death-1 blockade antibodies (anti-PD1) in heavily pre-treated
      patients with classical Hodgkin lymphoma (HL). To this end, we evaluated the
      kinetics of response for up to two years. MATERIALS AND METHODS: The 18F-FDG
      positron-emission tomography (PET) and contrast-enhanced computerised tomography
      (CECT) data of all relapsed or refractory HL treated at Gustave Roussy,
      Villejuif, France, from 2013 to 2015 were retrospectively reviewed according to
      the International Harmonisation Project Cheson 2014 criteria and the LYmphoma
      Response to Immunomodulatory therapy Criteria (LYRIC). RESULTS: Sixteen patients
      were included. The median (range) treatment duration was 18.4 (2.8-23.7) months.
      Fifty-six percent of patients (9/16) achieved an objective response at 3 months,
      including 19% (3/16) of complete response. Seventeen percent (1/6) of partial
      responders at 3 months were converted in a complete response. 22% (2/9) of
      responders at 3 months relapsed before one year. The nadir was reached at 12.7
      (3.0-23.0) months. The median (range) depth of response at nadir was -77% (-50%
      to 100%). CONCLUSION: We concluded that complete metabolic responses occurred
      within 6 months, a minority of partial responses were converted in complete
      response, and the median nadir was observed one year after treatment initiation.
      These data could help to better define the optimal treatment strategy by PET or
      CECT-directed approaches.

PMID- 29360606
TI  - The expression pattern and potential functions of PHB in the spermiogenesis of
      Phascolosoma esculenta.
AB  - Prohibitin (PHB) is a ubiquitous, evolutionarily conserved protein that is mainly
      localized in the inner mitochondrial membrane and exerts various mitochondrial
      functions. Here, we first cloned the phb gene from P. esculenta. The Pe-PHB
      protein has high homology and a similar protein structure to that of other
      animals, and it can be divided into the N-terminal hydrophobic/transmembrane
      domain, SPFH domain, and C-terminal coiled-coil domain. The Pe-phb gene is widely
      expressed, and the gene expression of phb is highest in coelomic fluid where
      spermiogenesis occurs, indicating a specific function in the coelom. We further
      observed continuous expression of the phb gene and localization of PHB proteins
      in mitochondria during spermiogenesis, indicating that PHB, as a mitochondrial
      component, may play a role during this process via its mitochondrial function. In
      addition, ubiquitination of mitochondria was detected, and the PHB signal was co
      localized with the poly-ubiquitin signal during spermiogenesis. Mature sperm also
      showed ubiquitination of mitochondria and PHB. Therefore, PHB may be a substrate
      of poly-ubiquitin to regulate the ubiquitination of mitochondria and even
      subsequent elimination during P. esculenta spermiogenesis, and it has a potential
      role in guaranteeing the maternal inheritance of mitochondria. Taken together,
      these results support the hypothesis that PHB participates in the spermiogenesis
      of P. esculenta by maintaining the normal function of mitochondria and regulating
      the degradation of mitochondria.

PMID- 29360607
TI  - Association between chemerin rs17173608 and rs4721 gene polymorphisms and
      gestational diabetes mellitus in Iranian pregnant women.
AB  - Gestational diabetes mellitus (GDM) is defined as hyperglycemia detected during
      pregnancy and its risk is increased with obesity. Chemerin, an adipokine, has
      been proposed as potential mediators of insulin resistance in GDM. This case
      control study was designed to assess the relation between chemerin SNPs rs4721
      (or rs10278590) and rs17173608 and the development of GDM. One hundred thirty GDM
      pregnant women with GDM and 160 healthy pregnant women were enrolled in this
      study. The diagnosis of GDM was based on the International Association of
      Diabetes and Pregnancy Study Group (IADPSG) criteria. Chemerin rs4721
      polymorphism gene was amplified through PCR, and SNP was detected using
      restriction enzyme AluI. Genotyping for chemerin rs17173608 polymorphism was
      performed by using tetra-amplification refractory mutation system polymerase
      chain reaction (T-ARMS-PCR). Blood glucose level was measured by an enzymatic
      method. Our finding showed that the genotypes frequency of chemerin rs4721
      polymorphism was significantly different between GDM and non-GDM groups (chi2 =
      7.44, P = 0.02). The genotype of rs4721 was significantly associated with GDM in
      co-dominant and dominant genotypes (GG vs GT, OR = 2.3, 95%CI = 1.24-4.24, P =
      0.008, and GG vs GT + TT, OR = 2.21, 95%CI = 1.23-3.99, P = 0.008, respectively).
      No significant difference was observed in allele frequency between case and
      control groups (P = 0.62). Moreover, the genotypes and allele frequencies of
      chemerin rs17173608 polymorphism did not show significant differences between GDM
      and non-GDM (P > 0.05). We concluded that the genotype of rs4721 was found to
      contribute significant risk to GDM while genotype of rs17173608 could not predict
      the risk of GDM.

PMID- 29360610
TI  - Early nutritional inadequacy is associated with psoas muscle deterioration and
      worse clinical outcomes in critically ill surgical patients.
AB  - PURPOSE: To explore whether psoas cross sectional area (CSA) and density
      (Hounsfield Units, HU) are associated with nutritional adequacy and clinical
      outcomes in surgical intensive care unit patients. MATERIALS AND METHODS:
      Subjects with at least one CT scan within 72h of ICU admission were included.
      Demographic, nutritional, radiographic, and outcomes data were collected. Psoas
      muscle CSA and HU were assessed at the L4-L5 intervertebral disk level. Change
      (Delta) in CSA and HU overall and per day were calculated. RESULTS: 140 patients
      were included. There was no significant correlation between baseline CSA and HU
      and clinical outcomes. Patients with at least two CT scans (n=65), had a median
      decrease in CSA of -15% [IQR: -20%, -8%] and decrease in HU of -2% [IQR: -30%,
      +24%]. Patients with the greatest daily %HU decline received significantly fewer
      calories/kg and proteins/kg and accumulated greater protein deficits at day 7 and
      overall. Patients with daily %HU increase had the shortest ICU and hospital LOS
      and more ventilator-free days in univariate and multivariable analyses.
      CONCLUSIONS: In this exploratory study, early nutritional deficits were
      correlated with muscle quality deterioration. Inpatient gain in psoas density,
      compared to maintenance or loss, is associated with shorter hospital stay.

PMID- 29360608
TI  - Resting Functional Connectivity of the Periaqueductal Gray Is Associated With
      Normal Inhibition and Pathological Facilitation in Conditioned Pain Modulation.
AB  - : Conditioned pain modulation (CPM), a psychophysical paradigm that is commonly
      used to infer the integrity of endogenous pain-altering systems by observation of
      the effect of one noxious stimulus on another, has previously identified
      deficient endogenous analgesia in fibromyalgia (FM) and other chronic pain
      conditions. The mechanisms underlying this deficiency, be they insufficient
      inhibition and/or active facilitation, are largely unknown. The present cross
      sectional study used a combination of behavioral CPM testing, voxel-based
      morphometry, and resting state functional connectivity to identify neural
      correlates of CPM in healthy controls (HC; n = 14) and FM patients (n = 15), and
      to probe for differences that could explain the pain-facilitative CPM that was
      observed in our patient sample. Voxel-based morphometry identified a cluster
      encompassing the periaqueductal gray (PAG) that contained significantly less gray
      matter volume in FM patients. Higher resting connectivity between this cluster
      and cortical pain processing regions was associated with more efficient
      inhibitory CPM in both groups, whereas PAG connectivity with the dorsal pons was
      associated with greater CPM inhibition only in HC. Greater PAG connectivity to
      the caudal pons/rostral medulla, which was pain-inhibitory in HC, was associated
      with pain facilitation in FM patients. PERSPECTIVE: These findings indicate that
      variation in the strength of the PAG resting functional connectivity can explain
      some of the normal variability in CPM. In addition, pain-facilitative CPM
      observed in FM patients likely involves attenuation of pain inhibitory as well as
      amplification of pain facilitative processes in the central nervous system.

PMID- 29360611
TI  - Higher tacrolimus blood concentration is related to increased risk of post
      transplantation diabetes mellitus after living donor liver transplantation.
AB  - BACKGROUND/AIMS: To investigate the association between tacrolimus (TAC) blood
      concentration and the risk of post-transplantation diabetes mellitus (PTDM)
      development after living donor liver transplantation (LDLT). METHODS: This study
      reviewed the clinical data of 158 adult LDLT recipients. A cut-off of mean trough
      concentration of TAC (cTAC) value at the sixth month postoperatively was
      identified using a receptor operating characteristic curve. Other clinical
      complications rates were compared between different cTAC groups. RESULTS: Thirty
      four (21.5%) recipients developed PTDM during follow-up period. Recipients with
      PTDM suffered lower 1-, 5- and 10-year overall survival rates (85.2%, 64.9%, and
      55.6% vs 92.4%, 81.4%, and 79.1%, p < 0.05) and allograft survival rates (87.9%,
      76.9%, and 65.9% vs 94.1%, 88.5%, and 86.0%, p < 0.05) than those without PTDM.
      The best cut-off value of mean cTAC was 5.9 ng/mL. Recipients with higher cTAC
      (>5.9 ng/mL) were more likely to develop hyperlipidemia (39.6% vs 21.9%, p <
      0.05), cardio-cerebral events (7.5% vs1.0%, p < 0.05), and infections (37.7%
      vs19.0%, p < 0.05) than recipients exposed to low cTAC (<=5.9 ng/mL). However,
      the two groups showed no difference in the incidence of acute and chronic
      rejection. CONCLUSION: Higher mean cTAC at the sixth month postoperatively is
      related to increased risk of PTDM in LDLT recipients.

PMID- 29360609
TI  - A model-based quantification of action control deficits in Parkinson's disease.
AB  - Basal ganglia dysfunction in Parkinson's disease (PD) is thought to generate
      deficits in action control, but the characterization of these deficits have been
      qualitative rather than quantitative. Patients with PD typically show prolonged
      response times on tasks that instantiate a conflict between goal-directed
      processing and automatic response tendencies. In the Simon task, for example, the
      irrelevant location of the stimulus automatically activates a corresponding
      lateralized response, generating a potential conflict with goal-directed choices.
      We applied a new computational model of conflict processing to two sets of
      behavioral data from the Simon task to quantify the effects of PD and
      dopaminergic (DA) medication on action control mechanisms. Compared to healthy
      controls (HC) matched in age gender and education, patients with PD showed a
      deficit in goal-directed processing, and the magnitude of this deficit positively
      correlated with cognitive symptoms. Analyses of the time-course of the location
      based automatic activation yielded mixed findings. In both datasets, we found
      that the peak amplitude of the automatic activation was similar between PD and
      HC, demonstrating a similar degree of response capture. However, PD patients
      showed a prolonged automatic activation in only one dataset. This discrepancy was
      resolved by theoretical analyses of conflict resolution in the Simon task. The
      reduction of interference generated by the automatic activation appears to be
      driven by a mixture of passive decay and top-down inhibitory control, the
      contribution of each component being modulated by task demands. Our results
      suggest that PD selectively impairs the inhibitory control component, a deficit
      likely remediated by DA medication. This work advances our understanding of
      action control deficits in PD, and illustrates the benefit of using computational
      models to quantitatively measure cognitive processes in clinical populations.

PMID- 29360612
TI  - Intracranial electrodes monitoring improves seizure control and complication
      outcomes for patients with temporal lobe epilepsy - A retrospective cohort study.
AB  - BACKGROUND: Anterior temporal lobectomy (ATL) is the standard surgical treatment
      for temporal lobe epilepsy (TLE), but patients may suffer from recurrent seizures
      post-surgery. Invasive electrical monitoring plays a critical role in precisely
      identifying the epileptic foci. This study aimed to evaluate and compare the
      benefits of long-term invasive electroencephalography (EEG) monitoring and two
      stage surgery with the classical approach to examine their effect on post
      surgical brain function and complications. MATERIALS AND METHODS: Patients with
      TLE (N = 198) who underwent epilepsy surgery were retrospectively evaluated.
      Diagnosis of TLE was confirmed based on clinical grounds (semiology), EEG
      findings, and magnetic resonance imaging (MRI). Long-term invasive video EEG was
      performed; epileptiform discharges were recorded. Patients underwent either
      classical ATL or modified two-step surgery with electrodes implantation.
      Histopathological examination was performed. The patients were followed up at 1,
      3, and 5 years after surgery. RESULTS: Twenty-three and 175 patients underwent
      classical ATL and two-stage surgery, respectively. On histopathological
      examination, inflammation, hippocampal sclerosis, and cortical dysplasia were
      found to be the leading pathological causes of epileptic foci in both groups. MRI
      results were not consistent with the pathological findings. Grade II and III
      Engel scores were more frequent in the ATL group compared to two-stage surgery
      during follow-up. No postoperative complications were reported in two-stage
      surgery during follow-up, but one patient had mild hemiplegia in the ATL group.
      CONCLUSIONS: Preoperative invasive monitoring with long-term EEG helps locate the
      epileptic foci precisely. Postsurgical complications are rare compared to
      classical ATL, with better prognosis and seizure freedom after surgery.

PMID- 29360613
TI  - Minimally invasive surgery versus open hepatectomy for hepatolithiasis: A
      systematic review and meta analysis.
AB  - OBJECTIVE: Hepatectomy for hepatolithiasis can be performed by following an open
      approach or a minimally invasive surgery (MIS) approach. MIS is associated with
      theoretical advantages, but there is no consensus regarding to the best treatment
      method for hepatolithiasis. The objective of this study was to evaluate the
      clinical outcomes of MIS hepatectomy compared with those of open hepatectomy in
      hepatolithiasis patients. METHODS: A systematic literature search was performed
      using PubMed, Embase and Cochrane Library databases. The data were analyzed with
      Stata version 12.0 software. Meta-regression analysis was used to explore the
      potential sources of heterogeneity. Egger's tests and Begg's funnel plots were
      employed to evaluate the publication biases. RESULTS: In total, 12 nonrandomized
      controlled trials were identified. Compared with open hepatectomy, the volume of
      intraoperative blood loss was significantly less in MIS hepatectomy (SMD = 
      0.226, P = 0.000). The intraoperative blood transfusion rate was also lower in
      MIS hepatectomy (RR = 0.569, P = 0.003). A shorter length of postoperative
      hospital stay was noted with MIS hepatectomy (SMD = -0.537, P = 0.000). MIS
      hepatectomy resulted in a lower rate of postoperative complications than open
      hepatectomy (RR = 0.595, P = 0.000). However, MIS hepatectomy resulted in a
      longer operation time (SMD = 0.473, P = 0.005). No significant differences were
      noted between MIS and open hepatectomy in the initial stone clearance rate (RR =
      1.33, P = 0.218), the final stone clearance rate (RR = 1.040, P = 0.131), the
      stone recurrence rate (RR = 0.558, P = 0.072) or the cholangitis recurrence rate
      (RR = 0.610, P = 0.285). CONCLUSIONS: MIS hepatectomy is a safe approach for
      hepatolithiasis patients. MIS hepatectomy significantly reduces intraoperative
      blood loss, blood transfusion, postoperative hospital stay time and
      complications. The stone clearance and recurrence rates were similar for MIS
      hepatectomy and open hepatectomy. Additional well-designed randomized controlled
      trials and Western studies are needed to confirm these findings.

PMID- 29360614
TI  - Impact of Multigene Panel Testing on Surgical Decision Making in Breast Cancer
      Patients.
AB  - BACKGROUND: With the advent of multigene panel testing for breast cancer
      patients, germline mutations with unknown association with cancer risk, known as
      variants of uncertain significance (VUS), are being increasingly identified. Some
      studies have shown higher rates of contralateral prophylactic mastectomies (CPM)
      in these patients, despite lack of evidence to support this intervention. We
      analyzed surgical choices in patients who were identified to have VUS. STUDY
      DESIGN: A retrospective review was performed of patients with triple-negative
      breast cancer treated at a single institution after multigene panel tests became
      available (September 1, 2013 to February 28, 2017). Rates of genetic testing,
      results of testing, and surgical decision making were evaluated. Chi-square or
      Fisher's exact test was used to compare categorical variables. A p value <0.05
      was considered statistically significant. RESULTS: There were 477 triple-negative
      breast cancer patients identified; 331 met established criteria for genetic
      testing and 226 (68.3%) underwent genetic testing (multigene panel, n = 130 and
      BRCA1/2 testing, n = 96). All of them received risk-appropriate genetic
      counseling and follow-up. Of these, 29 (12.8%) patients had pathogenic mutations
      in BRCA1/2 or PALB2 (Mut+), 42 (18.6%) had VUS (VUS+), and 155 (68.6%) had no
      mutations identified (Mut-). Variants of uncertain significance in 6 of 42
      patients (14.3%) were later reclassified as normal variants. Eighty-eight percent
      of Mut+ patients underwent CPM compared with 20.1% of Mut- and 21.4% of VUS+
      patients (p < 0.001 for both). Rates of CPM were not significantly different
      between VUS+ and Mut- (p = 0.37). Multigene panel testing detected pathogenic
      mutations in non-breast cancer-associated genes in 6 patients, with significant
      management implications. CONCLUSIONS: When combined with risk-appropriate genetic
      counseling, detection of VUS did not lead to excessive CPM in this cohort of
      triple-negative breast cancer patients. Furthermore, panel testing detected
      mutations in non-breast cancer-associated genes, which had significant
      implications on management and outcomes.

PMID- 29360615
TI  - Patient and Graft Survival: Biliary Complications after Liver Transplantation.
AB  - BACKGROUND: Biliary complications (BCs) affect up to to 34% of liver transplant
      recipients and are a major source of morbidity and cost. This is a 13-year review
      of BCs after liver transplantation (LT) at a tertiary care center. STUDY DESIGN:
      We conducted a single-center retrospective review of our prospective database to
      assess BCs in adult (aged 18 years or older) liver transplant recipients during a
      13-year period (2002 to 2014). Biliary complications were divided into 3
      subgroups: leak alone (L), stricture alone (S), and both leak and strictures
      (LS). Controls (no BCs) were used for comparison. RESULTS: There were 1,041 adult
      LTs performed during the study period; BCs developed in 239 (23%) of these
      patients: 55 (23%) L, 148 (62%) S, and 36 (15%) LS. One hundred and two (43%)
      were early (less than 30 d). Surgical revision was required in 42 cases (17%) (30
      L, 10 LS, and 2 S), while the remaining 197 (83%) were managed nonsurgically (25
      L, 26 LS, and 146 S), with a mean of 4.2 interventions/patient. One-, 3-, and 5
      year overall patient and graft survival was significantly reduced in patients
      with bile leaks (84%, 71%, and 68% and 76%, 67%, and 64%, respectively) compared
      with controls (90%, 84%, and 78% and 88%, 81%, and 76%, respectively [p < 0.05]).
      Patients with BCs had higher incidence of cholestatic liver disease, higher pre
      LT bilirubin, higher use of T-tubes, higher use of donor after cardiac death
      grafts, and higher rates of acute rejection (p < 0.05). Patients with BCs had
      longer ICU and hospital stays and higher rates of 30- and 90-day readmissions (p
      < 0.01). Multivariate analysis identified cholestatic liver disease, Roux-en-Y
      anastomosis, donor risk index >2, and T-tubes as independent BC predictors.
      CONCLUSIONS: Biliary complications after LT can significantly decrease patient
      and graft survival rates. Careful donor and recipient selection and attention to
      anastomotic technique can reduce BCs and improve outcomes.

PMID- 29360616
TI  - Variation in Amputation Risk for Black Patients: Uncovering Potential Sources of
      Bias and Opportunities for Intervention.
AB  - BACKGROUND: Differences in amputation rates for limb ischemia between white and
      black patients have been extensively studied. Our goal was to determine whether
      biases in provider decision-making contribute to the disparity. We hypothesized
      that the magnitude of the disparity is affected by surgeon and hospital factors.
      STUDY DESIGN: Analysis of the New York Statewide Planning and Research
      Cooperative System database was performed for 1999 to 2014. Black and white
      patients with ICD9 codes for peripheral vascular disease, who received either an
      amputation or salvage procedure, were included. The primary endpoint was
      treatment choice. RESULTS: We analyzed 215,480 inpatient admissions. The overall
      amputation rate was 38.0%, and blacks were significantly more likely to receive
      amputations than whites on unadjusted (42.6% vs 28.6%, p < 0.001), and
      multivariable analyses (odds ratio [OR] 1.45, 95% CI 1.31 to 1.60, p < 0.001).
      This difference was more pronounced among high total vascular volume surgeons (OR
      1.74, 95% CI 1.50 to 2.00, p < 0.001), but not among those with low total
      vascular volume (OR 1.06, 95% CI 0.90 to 1.24, p = 0.49); high volume hospitals
      (OR 1.57, 95% CI 1.39 to 1.78, p < 0.001), but not among those with low
      amputation volume (OR 0.96, 95% CI 0.73 to 1.27, p < 0.80); and surgeons who
      treat fewer black patients (OR 1.58, 95% CI 1.44 to 1.73, p < 0.001) vs surgeons
      who see more black patients (OR 1.43, 95% CI 1.30 to 1.57, p < 0.0.001).
      CONCLUSIONS: Black patients are significantly more likely to receive an
      amputation than a salvage procedure when presenting with significant peripheral
      vascular diseases. High procedural volume does not seem to reduce unequal
      treatment; diversity of surgeon practice does.

PMID- 29360617
TI  - High diversity, high insular endemism and recent origin in the lichen genus
      Sticta (lichenized Ascomycota, Peltigerales) in Madagascar and the Mascarenes.
AB  - Lichen biodiversity and its generative evolutionary processes are practically
      unknown in the MIOI (Madagascar and Indian Ocean Islands) biodiversity hotspot.
      We sought to test the hypothesis that lichenized fungi in this region have
      undergone a rapid radiation, following a single colonization event, giving rise
      to narrow endemics, as is characteristic of other lineages of plants. We
      extensively sampled specimens of the lichen genus Sticta in the Mascarene
      archipelago (mainly Reunion) and in Madagascar, mainly in the northern range
      (Amber Mt and Marojejy Mt) and produced the fungal ITS barcode sequence for 148
      thalli. We further produced a four-loci data matrix for 68 of them, representing
      the diversity and geographical distribution of ITS haplotypes. We reconstructed
      the phylogenetic relationships within this group, established species boundaries
      with morphological context, and estimated the date of the most recent common
      ancestor. Our inferences resolve a robust clade comprising 31 endemic species of
      Sticta that arose from the diversification following a single recent (c. 11 Mya)
      colonization event. All but three species have a very restricted range, endemic
      to either the Mascarene archipelago or a single massif in Madagascar. The first
      genus of lichens to be studied with molecular data in this region underwent a
      recent radiation, exhibits micro-endemism, and thus exemplifies the biodiversity
      characteristics found in other taxa in Madagascar and the Mascarenes.

PMID- 29360618
TI  - Plastid phylogenomics resolves infrafamilial relationships of the Styracaceae and
      sheds light on the backbone relationships of the Ericales.
AB  - Relationships among the genera of the small, woody family Styracaceae and among
      families of the large, diverse order Ericales have resisted complete resolution
      with sequences from one or a few genes. We used plastome sequencing to attempt to
      resolve the backbone relationships of Styracaceae and Ericales and to explore
      plastome structural evolution. Complete plastomes for 23 species are newly
      reported here, including 18 taxa of Styracaceae and five of Ericales (including
      species of Sapotaceae, Clethraceae, Symplocaceae, and Diapensiaceae). Combined
      with publicly available complete plastome data, this resulted in a data set of 60
      plastomes, including 11 of the 12 genera of Styracaceae and 12 of 22 families of
      Ericales. Styracaceae plastomes were found to possess the quadripartite structure
      typical of angiosperms, with sizes ranging from 155 to 159 kb. Most of the
      plastomes were found to possess the full complement of typical angiosperm
      plastome genes. Unusual structural features were detected in plastomes of
      Alniphyllum and Bruinsmia, including the presence of a large 20-kb inversion (14
      genes) in the Large Single-Copy region, the loss or pseudogenization of the clpP
      and accD genes in Bruinsmia, and the loss of the first exon of rps16 in B.
      styracoides. Likewise, the second intron from clpP was found to be lost in
      Alniphyllum and Huodendron. Phylogenomic analyses including all 79 plastid
      protein-coding genes provided improved resolution for relationships among the
      genera of Styracaceae and families of Ericales. Styracaceae was strongly
      supported as monophyletic, with Styrax, Huodendron, and a clade of Alniphyllum +
      Bruinsmia successively sister to the remainder of the family, all with strong
      support. All genera of Styracaceae were recovered as monophyletic, except for
      Halesia and Pterostyrax, which were each recovered as polyphyletic with strong
      support. Within Ericales, all families were recovered as monophyletic with strong
      support, with Balsaminaceae sister to remaining Ericales. Most relationships
      recovered in plastome analyses are congruent with previous analyses based on
      smaller data sets. Our results demonstrate the power of plastid phylogenomics to
      improve phylogenetic hypotheses among genera and families, and provide new
      insight into plastome evolution across Ericales.

PMID- 29360619
TI  - Hypophosphatasia: Biochemical hallmarks validate the expanded pediatric clinical
      nosology.
AB  - Hypophosphatasia (HPP) is the inborn-error-of-metabolism due to loss-of-function
      mutation(s) of the ALPL (TNSALP) gene that encodes the tissue non-specific
      isoenzyme of alkaline phosphatase (TNSALP). TNSALP represents a family of cell
      surface phosphohydrolases differing by post-translational modification that is
      expressed especially in the skeleton, liver, kidney, and developing teeth. Thus,
      the natural substrates of TNSALP accumulate extracellularly in HPP including
      inorganic pyrophosphate (PPi), a potent inhibitor of mineralization, and
      pyridoxal 5'-phosphate (PLP), the principal circulating form of vitamin B6. The
      superabundance of extracellular PPi regularly causes tooth loss, and when
      sufficiently great can lead to rickets or osteomalacia. Sometimes diminished
      hydrolysis of PLP engenders vitamin B6-dependent seizures in profoundly affected
      babies. Autosomal dominant and autosomal recessive inheritance from among >340
      ALPL mutations identified to date, typically missense and located throughout the
      gene, largely explains the remarkably wide-ranging severity of HPP, greatest of
      all skeletal diseases. In 2015, our demographic, clinical, and DXA findings
      acquired over 25 years from 173 children and adolescents with HPP validated and
      expanded the clinical nosology for pediatric patients to include according to
      increasing severity "odonto" HPP, "mild childhood" HPP, "severe childhood" HPP,
      "infantile" HPP, and "perinatal" HPP. Herein, we assessed this expanded nosology
      using biochemical hallmarks of HPP. We evaluated exclusively data from the 165
      preteenage HPP patients in this cohort to exclude potential effects from
      physiological changes in TNSALP levels across puberty. All patients had subnormal
      serum total and bone-specific ALP and elevated plasma PLP, and nearly all had
      excessive urinary PPi excretion. Only the PLP levels were unchanged across
      puberty. Mean levels of all four biomarkers correlated with HPP severity ranked
      according to the HPP nosology, but the data overlapped among all four patient
      groups. Hence, these four biochemical hallmarks represent both a sensitive and
      reliable tool for diagnosing children with HPP. Furthermore, the hallmarks
      validate our expanded clinical nosology for pediatric HPP that, with limitations,
      is an improved framework for conceptualizing and working with this disorder's
      remarkably broad-ranging severity.

PMID- 29360620
TI  - Bone marrow adipocytes resist lipolysis and remodeling in response to beta
      adrenergic stimulation.
AB  - Bone marrow adipose tissue (BMAT) is preserved or increased in states of caloric
      restriction. Similarly, we found that BMAT in the tail vertebrae, but not the red
      marrow in the tibia, resists loss of neutral lipid with acute, 48-hour fasting in
      rats. The mechanisms underlying this phenomenon and its seemingly distinct
      regulation from peripheral white adipose tissue (WAT) remain unknown. To test the
      role of beta-adrenergic stimulation, a major regulator of adipose tissue
      lipolysis, we examined the responses of BMAT to beta-adrenergic agonists.
      Relative to inguinal WAT, BMAT had reduced phosphorylation of hormone sensitive
      lipase (HSL) after treatment with pan-beta-adrenergic agonist isoproterenol.
      Phosphorylation of HSL in response to beta3-adrenergic agonist CL316,243 was
      decreased by an additional ~90% (distal tibia BMAT) or could not be detected
      (tail vertebrae). Ex vivo, adrenergic stimulation of lipolysis in purified BMAT
      adipocytes was also substantially less than iWAT adipocytes and had site-specific
      properties. Specifically, regulated bone marrow adipocytes (rBMAs) from proximal
      tibia and femur underwent lipolysis in response to both CL316,243 and forskolin,
      while constitutive BMAs from the tail responded only to forskolin. This occurred
      independently of changes in gene expression of beta-adrenergic receptors, which
      were similar between adipocytes from iWAT and BMAT, and could not be explained by
      defective coupling of beta-adrenergic receptors to lipolytic machinery through
      caveolin 1. Specifically, we found that whereas caveolin 1 was necessary to
      mediate maximal stimulation of lipolysis in iWAT, overexpression of caveolin 1
      was insufficient to rescue impaired BMAT signaling. Lastly, we tested the ability
      of BMAT to respond to 72-hour treatment with CL316,243 in vivo. This was
      sufficient to cause beiging of iWAT adipocytes and a decrease in iWAT adipocyte
      cell size. By contrast, adipocyte size in the tail BMAT and distal tibia remained
      unchanged. However, within the distal femur, we identified a subpopulation of
      BMAT adipocytes that underwent lipid droplet remodeling. This response was more
      pronounced in females than in males and resembled lipolysis-induced lipid
      partitioning rather than traditional beiging. In summary, BMAT has the capacity
      to respond to beta-adrenergic stimuli, however, its responses are muted and BMAT
      generally resists lipid hydrolysis and remodeling relative to iWAT. This
      resistance is more pronounced in distal regions of the skeleton where the BMAT
      adipocytes are larger with little intervening hematopoiesis, suggesting that
      there may be a role for both cell-autonomous and microenvironmental determinants.
      Resistance to beta-adrenergic stimuli further separates BMAT from known
      regulators of energy partitioning and contributes to our understanding of why
      BMAT is preserved in states of fasting and caloric restriction.

PMID- 29360621
TI  - Effects of cultural education and cultural experiences on the cultural competence
      among undergraduate nursing students.
AB  - Because of globalization and growing immigrant populations, nursing students need
      to possess a high level of cultural competence to provide nursing care to
      patients from various cultural backgrounds. However, it has been reported that
      the current cultural education in nursing curriculums is not sufficient to
      improve students' cultural competence. Little is known about how nursing
      students' personal experiences of other cultures may impact their cultural
      competence. This study was conducted to identify the ways in which cultural
      education and personal experiences with other cultures affect nursing students'
      cultural competence. A questionnaire-based descriptive cross-sectional study was
      conducted with 236 Korean nursing students from four universities in South Korea.
      The explanatory power of cultural experiences and cultural education for nursing
      students' cultural competence was 8.1% and 7.1%, respectively. The present study
      revealed that the explanatory power of the variable for nursing students'
      cultural competence increased when cultural experiences were added to cultural
      education. Among cultural experiences, contact with people from other cultural
      areas influenced nursing students' cultural competence the most. Therefore, it is
      recommended to encourage nursing students to engage in extracurricular activities
      with people from other countries, adding this to organized lectures on cultural
      education.

PMID- 29360622
TI  - Prognostic analysis according to the 2017 ELN risk stratification by genetics in
      adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study
      Group (JALSG) AML201 study.
AB  - Many genetic alterations that are associated with the prognosis of acute myeloid
      leukemia (AML) have been identified, and several risk stratification systems
      based on the genetic status have been recommended. The European LeukemiaNet (ELN)
      first proposed the risk stratification system for AML in 2010 (ELN-2010), and
      recently published the revised system (ELN-2017). We validated the long-term
      prognosis and clinical characteristics of each ELN-2017 risk category in Japanese
      adult AML patients who were treated in the Japan Adult Leukemia Study Group
      (JALSG) AML-201 study. We demonstrated that the 3-risk category system of the ELN
      2017 successfully discriminated the overall survival and complete remission rates
      in our cohort in comparison with the 4-risk category of the ELN-2010. However,
      there were still genetic categories in which stratification of patients into
      favorable or intermediate risk categories was controversial; the low allelic
      ratio of FLT3-ITD was not necessarily associated with a better prognosis in
      patients with FLT3-ITD, and cytogenetic abnormalities may affect the prognosis in
      patients with favorable genetic lesions such as NPM1 and CEBPA mutations. As many
      molecular targeting agents, such as FLT3 inhibitors, have been developed, we must
      continue to modify the genetic risk stratification system to match the
      progression of therapeutic strategies.

PMID- 29360623
TI  - Age-related mechanism and its relationship with secondary metabolism and abscisic
      acid in Aristotelia chilensis plants subjected to drought stress.
AB  - Drought stress is the most important stress factor for plants, being the main
      cause of agricultural crop loss in the world. Plants have developed complex
      mechanisms for preventing water loss and oxidative stress such as synthesis of
      abscisic acid (ABA) and non-enzymatic antioxidant compounds such as anthocyanins,
      which might help plants to cope with abiotic stress as antioxidants and for
      scavenging reactive oxygen species. A. chilensis (Mol.) is a pioneer species,
      colonizing and growing on stressed and disturbed environments. In this research,
      an integrated analysis of secondary metabolism in Aristotelia chilensis was done
      to relate ABA effects on anthocyanins biosynthesis, by comparing between young
      and fully-expanded leaves under drought stress. Plants were subjected to drought
      stress for 20 days, and physiological, biochemical, and molecular analyses were
      performed. The relative growth rate and plant water status were reduced in
      stressed plants, with young leaves significantly more affected than fully
      expanded leaves beginning from the 5th day of drought stress. A. chilensis plants
      increased their ABA and total anthocyanin content and showed upregulation of gene
      expression when they were subjected to severe drought (day 20), with these
      effects being higher in fully-expanded leaves. Multivariate analysis indicated a
      significant positive correlation between transcript levels for NCED1 (9-cis
      epoxycarotenoid dioxygenase) and UFGT (UDP glucose: flavonoid-3-O
      glucosyltransferase) with ABA and total anthocyanin, respectively. Thus, this
      research provides a more comprehensive analysis of the mechanisms that allow
      plants to cope with drought stress. This is highlighted by the differences
      between young and fully-expanded leaves, showing different sensibility to stress
      due to their ability to synthesize anthocyanins. In addition, this ability to
      synthesize different and high amounts of anthocyanins could be related to higher
      NCED1 and MYB expression and ABA levels, enhancing drought stress tolerance.

PMID- 29360625
TI  - Meeting report - shining light on septins.
AB  - Septins are enigmatic proteins; they bind GTP and assemble together like
      molecular Lego blocks to form intracellular structures of varied shapes such as
      filaments, rings and gauzes. To shine light on the biological mysteries of septin
      proteins, leading experts in the field came together for the European Molecular
      Biology Organization (EMBO) workshop held from 8-11 October 2017 in Berlin.
      Organized by Helge Ewers (Freie Universitat, Berlin, Germany) and Serge Mostowy
      (Imperial College, London, UK), the workshop convened at the Harnack-Haus, a
      historic hub of scientific discourse run by the Max Planck Society.

PMID- 29360624
TI  - Association of processed food, synergistic effect of alcohol and HBV with
      Hepatocellular Carcinoma in a high incidence region of India.
AB  - BACKGROUND: Dietary factors, tobacco, and alcohol use have been identified as
      important factors of rising various cancer incidence in several northeastern
      states of India. However, little is known about the factors associated with
      hepatocellular carcinoma (HCC) in this region. The aim of the paper was to
      identify the factors associated with HCC in the northeast region. METHODS: A case
      control study was conducted in Arunachal Pradesh and Sikkim, two northeastern
      states of India, including 104 histologically-confirmed cases of HCC and same
      number (104) of age and sex matched control enrolled. Logistic regression
      analysis was performed to identify the factors associated with HCC. RESULTS: A
      statistically significant association was demonstrated between HCC and alcohol
      consumption, consumption of 'Sai-mod' (OR 2.77, CI 1.57-4.87) a homemade alcohol
      beverage, and with HBV (OR 7.97, CI 3.36-18.94). Positive synergism index (S =
      3.04) was observed between HBV and alcohol consumption to risk of HCC. Higher
      intake of processed meat (OR 2.56, CI 1.09-6.03) and processed fish (OR 2.24, CI
      1.02-4.95) were found associated with increased risk of HCC; and decreased risk
      of HCC with fresh fish, fruits, and milk. CONCLUSIONS: Strong relationship
      between different dietary factors, alcohol beverage with HCC suggests that
      control on dietary and drinking habit will be an important strategy to combat HCC
      in this region. Risk factors identified in this study will help to plan more
      effectively targeted risk reduction strategies and programs in this region.

PMID- 29360626
TI  - Meeting report - Cellular dynamics: membrane-cytoskeleton interface.
AB  - The first ever 'Cellular Dynamics' meeting on the membrane-cytoskeleton interface
      took place in Southbridge, MA on May 21-24, 2017 and was co-organized by Michael
      Way, Elizabeth Chen, Margaret Gardel and Jennifer Lippincott-Schwarz.
      Investigators from around the world studying a broad range of related topics
      shared their insights into the function and regulation of the cytoskeleton and
      membrane compartments. This provided great opportunities to learn about key
      questions in various cellular processes, from the basic organization and
      operation of the cell to higher-order interactions in adhesion, migration,
      metastasis, division and immune cell interactions in different model organisms.
      This unique and diverse mix of research interests created a stimulating and
      educational meeting that will hopefully continue to be a successful meeting for
      years to come.

PMID- 29360627
TI  - Launaea taraxacifolia (Willd.) Amin ex C. Jeffrey inhibits oxidative damage and
      econucleotidase followed by increased cellular ATP in testicular cells of rats
      exposed to metropolitan polluted river water.
AB  - BACKGROUND: Humans are directly/indirectly exposed to hazardous chemicals from
      the aquatic environment. We investigated the protection of the Launea
      taraxacifolia methanolic extract (LTME) on the hydroxyl steroid dehydrogenases
      [(?5-3beta-hydroxyl steroid dehydrogenase (?5-3beta-HSD) and the ?5-17beta
      hydroxyl steroid dehydrogenase (?5-17beta-HSD), testicular 5'-nucleotidase and
      lactate dehydrogenase (LDH)] activities as well as the key indicators of
      oxidative stress in germinal epithelial cells of rats induced with surulere
      polluted river water (SPRW). METHODS: The animals were divided into six groups
      (n=8). Group I was given 1 mL of distilled water only, Group II received 1 mL of
      SPRW only, Group III received 200 mg/kg LTME before+1 mL of SPRW after, Group IV
      received 200 mg/kg LTME+1 mL of SPRW, Group V received 1 mL of SPRW before+200
      mg/kg LTME after and Group VI received 200 mg/kg LTME only. The treatment was
      done via oral administration for 28 days. RESULTS: The HPLC results showed the
      abundance of quercetin and quercitrin. The SPRW increased 5'-nucleotidase with
      the concomitant decrease of ?5-3beta-HSD, ?5-17beta-HSD and LDH activities in
      rats exposed in relation to the control. Similarly, the administration of the
      SPRW caused a systemic oxidative damage along with adverse histopathological
      changes in germinal epithelial cells. CONCLUSIONS: Interestingly, these
      alterations were differentially reversed by LTME via the elevation of
      steroidogenic enzymes and cellular ATP.

PMID- 29360628
TI  - PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and
      review of the literature.
AB  - BACKGROUND: PHKG2 gene mutation can lead to liver phosphorylase kinase (PhK)
      deficiency, which is related to glycogen storage disease type IX (GSD IX). GSD
      IXc due to PHKG2 mutation is the second most common GSD IX. METHODS: We
      identified a novel mutation (c.553C>T, p.Arg185X) in PHKG2 in a Chinese family
      and verified it by next-generation and Sanger sequencing. The mutation spectrum
      of the PHKG2 gene was summarized based on 25 GSD IXc patients with PHKG2
      mutations. RESULTS: We found that missense mutation (39%) was the most common
      type of mutation, followed by nonsense mutation (23%). Mutations were more
      prevalent in Asian (12/25) and European (9/25) populations than in populations
      from elsewhere. The exons had more sites of mutation than the introns, and exons
      3 and 6 were the most frequent sites of mutations. CONCLUSIONS: This study
      expands our knowledge of the PHKG2 gene mutation spectrum, providing a molecular
      basis for GSD IXc.

PMID- 29360629
TI  - The immunopathogenesis of Zika virus: an overview.

PMID- 29360630
TI  - Impact of dermatologic adverse reactions on QOL in oncologic patients: results
      from a single-center prospective study.
AB  - INTRODUCTION: Skin toxicity in patients receiving novel therapeutic cancer agents
      has become a very important marker in determining drug activity, but it can also
      severely impact their quality of life. About half of the patients receiving this
      type of oncologic treatment will develop cutaneous reactions, that is why
      adequate understanding and management of these side effects is very important for
      drug adherence and patients' quality of life. MATERIALS AND METHODS: We conducted
      a prospective study of consecutive patients who received oncologic treatment in
      our institution and presented with dermatologic side effects. The severity of
      skin toxicity was assessed using the DLQI score and patients were prospectively
      followed to evaluate response to therapy. Univariate analysis of factors
      influencing the impact of skin toxicity on patient QOL was conducted. RESULTS: 52
      patients were enrolled in the study. Patients who developed grade 3 and 4 skin
      toxicity had a higher DLQI score, with a greater impact on quality of life, but
      with better clinical outcome at 3 months follow-up, based on RECIST. Patients
      with moderate or severe cutaneous AE were more likely to achieve complete or
      partial response to therapy than those with mild AE (16/33 vs. 3/19, p = 0.035).
      Interestingly, female patients had a significantly poorer quality of life than
      male patients as assessed by the DLQI score (7.28 +/- 7 vs. 3.7 +/- 3.6, p =
      0.038). CONCLUSION: Cutaneous side effects are often encountered in cancer
      patients and their severity can be a surrogate marker for a positive clinical
      tumor response to therapy.

PMID- 29360631
TI  - Proof-of-concept: 3D bioprinting of pigmented human skin constructs.
AB  - Three-dimensional (3D) pigmented human skin constructs have been fabricated using
      a 3D bioprinting approach. The 3D pigmented human skin constructs are obtained
      from using three different types of skin cells (keratinocytes, melanocytes and
      fibroblasts from three different skin donors) and they exhibit similar
      constitutive pigmentation (pale pigmentation) as the skin donors. A two-step drop
      on-demand bioprinting strategy facilitates the deposition of cell droplets to
      emulate the epidermal melanin units (pre-defined patterning of keratinocytes and
      melanocytes at the desired positions) and manipulation of the microenvironment to
      fabricate 3D biomimetic hierarchical porous structures found in native skin
      tissue. The 3D bioprinted pigmented skin constructs are compared to the pigmented
      skin constructs fabricated by conventional a manual-casting approach; in-depth
      characterization of both the 3D pigmented skin constructs has indicated that the
      3D bioprinted skin constructs have a higher degree of resemblance to native skin
      tissue in term of the presence of well-developed stratified epidermal layers and
      the presence of a continuous layer of basement membrane proteins as compared to
      the manually-cast samples. The 3D bioprinting approach facilitates the
      development of 3D in vitro pigmented human skin constructs for potential
      toxicology testing and fundamental cell biology research.

PMID- 29360632
TI  - Improved field emission properties of alpha-Fe2O3 nanoflakes with current aging
      treatment and morphology optimization.
AB  - alpha-Fe2O3 nanomaterials were synthesized by thermal oxidation of pure iron foil
      and the effects of current aging treatment and morphology on their field emission
      properties were systematically investigated. The current aging treatment was
      found to be an efficient method to improve the field emission properties of alpha
      Fe2O3 nanoflakes. The emission current density was largely enhanced from 0.05
      5.70 mA cm-2 under an applied electrical field of 7.8 MV m-1, and their threshold
      field decreased from than 11.0-6.6 MV m-1 after the current aging treatment. The
      mechanism of the improvement in the field emission performance of alpha-Fe2O3
      nanoflakes induced by the current aging treatment is discussed. alpha-Fe2O3
      nanostructures with various morphologies were synthesized by adjusting the growth
      temperatures between 300  degrees C-450  degrees C to optimize their
      morphologies. alpha-Fe2O3 nanoflakes synthesized at 350  degrees C were superior
      field emitters with a low threshold field of 5.1 MV m-1, high current density of
      63.4 mA cm-2, and stable emission, which demonstrated that alpha-Fe2O3 nanoflakes
      could be a promising material for application as field emitters.

PMID- 29360633
TI  - Tunable photovoltaic performance of preferentially oriented rutile TiO2 nanorod
      photoanode based dye sensitized solar cells with quasi-state electrolyte.
AB  - Photoanodes made of highly oriented TiO2 nanorod (NR) arrays with different
      aspect ratios were synthesized via a one-step hydrothermal technique.
      Preferentially oriented single crystalline rutile TiO2 was confirmed by the
      single peak in an XRD pattern (2theta = 63 degrees , (0 0 2)). FESEM images
      evidenced the growth of an array of NRss having different geometries with respect
      to reaction time and solution refreshment rate. The length, diameter and aspect
      ratio of the NRs increased with reaction time as 4 h (1.98 MUm, 121 nm, 15.32), 8
      h (4 MUm, 185 nm, 22.70), 12 h (5.6 MUm, 242 nm, 27.24) and 16 h (8 MUm, 254 nm,
      38.02), respectively. Unlike a conventional dye-sensitized solar cell (DSSC) with
      a liquid electrolyte, DSSCs were fabricated here using one-dimensional rutile
      TiO2 NR based photoanodes, N719 dye and a quasi-state electrolyte. The charge
      transport properties were investigated using current-voltage curves and fitted
      using the one-diode model. Interestingly the photovoltaic performance of the
      DSSCs increased exponentially with the length of the NR and was attributed to a
      higher surface to volume ratio, more dye anchoring, and channelized electron
      transport. The higher photovoltaic performance (Jsc = 5.99 mA cm-2, Voc = 750 mV,
      eta = 3.08%) was observed with photoanodes (16 h) made with the longer, densely
      packed TiO2 NRs (8 MUm, 254 nm).

PMID- 29360634
TI  - The most challenging cases.

PMID- 29360635
TI  - Remote retainer fabrication using teledentistry.

PMID- 29360636
TI  - 2017 JCO Orthodontic Practice Study: Part 2 Practice Success.

PMID- 29360637
TI  - Anterior open-bite correction with miniscrew anchorage and a combination of upper
      lingual and lower labial appliances.

PMID- 29360638
TI  - The easy driver for placement of palatal mini-implants and a maxillary expander
      in a single appointment.

PMID- 29360639
TI  - A new appliance for efficient molar distalization.

PMID- 29360640
TI  - Biocreative torque-maintaining archwire for adult patients with pathologically
      migrated incisors.

PMID- 29360641
TI  - COP1/DET1/ETS axis regulates ERK transcriptome and sensitivity to MAPK
      inhibitors.
AB  - Aberrant activation of MAPK signaling leads to the activation of oncogenic
      transcriptomes. How MAPK signaling is coupled with the transcriptional response
      in cancer is not fully understood. In 2 MAPK-activated tumor types,
      gastrointestinal stromal tumor and melanoma, we found that ETV1 and other Pea3
      ETS transcription factors are critical nuclear effectors of MAPK signaling that
      are regulated through protein stability. Expression of stabilized Pea3-ETS
      factors can partially rescue the MAPK transcriptome and cell viability after MAPK
      inhibition. To identify the players involved in this process, we performed a
      pooled genome-wide RNAi screen using a fluorescence-based ETV1 protein stability
      sensor and identified COP1, DET1, DDB1, UBE3C, PSMD4, and COP9 signalosome
      members. COP1 or DET1 loss led to decoupling between MAPK signaling and the
      downstream transcriptional response, where MAPK inhibition failed to destabilize
      Pea3 factors and fully inhibit the MAPK transcriptome, thus resulting in
      decreased sensitivity to MAPK pathway inhibitors. We identified multiple COP1 and
      DET1 mutations in human tumors that were defective in the degradation of Pea3-ETS
      factors. Two melanoma patients had de novo DET1 mutations arising after
      vemurafenib treatment. These observations indicate that MAPK signaling-dependent
      regulation of Pea3-ETS protein stability is a key signaling node in oncogenesis
      and therapeutic resistance to MAPK pathway inhibition.

PMID- 29360643
TI  - Tumor-infiltrating BRAFV600E-specific CD4+ T cells correlated with complete
      clinical response in melanoma.
AB  - T cells specific for neoantigens encoded by mutated genes in cancers are
      increasingly recognized as mediators of tumor destruction after immune checkpoint
      inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens
      result from random mutations and are patient specific, and some cancers contain
      few mutations to serve as potential antigens. We describe a patient with stage IV
      acral melanoma who achieved a complete response following adoptive transfer of
      tumor-infiltrating lymphocytes (TILs). Tumor exome sequencing surprisingly
      revealed fewer than 30 nonsynonymous somatic mutations, including oncogenic
      BRAFV600E. Analysis of the specificity of TILs identified rare CD4+ T cells
      specific for BRAFV600E and diverse CD8+ T cells reactive to nonmutated self
      antigens. These specificities increased in blood after TIL transfer and persisted
      long-term, suggesting they contributed to the effective antitumor immune
      response. Gene transfer of the BRAFV600E-specific T cell receptor (TCR) conferred
      recognition of class II MHC-positive cells expressing the BRAF mutation. Therapy
      with TCR-engineered BRAFV600E-specific CD4+ T cells may have direct antitumor
      effects and augment CD8+ T cell responses to self- and/or mutated tumor antigens
      in patients with BRAF-mutated cancers.

PMID- 29360642
TI  - Tie2 protects the vasculature against thrombus formation in systemic
      inflammation.
AB  - Disordered coagulation contributes to death in sepsis and lacks effective
      treatments. Existing markers of disseminated intravascular coagulation (DIC)
      reflect its sequelae rather than its causes, delaying diagnosis and treatment.
      Here we show that disruption of the endothelial Tie2 axis is a sentinel event in
      septic DIC. Proteomics in septic DIC patients revealed a network involving
      inflammation and coagulation with the Tie2 antagonist, angiopoietin-2 (Angpt-2),
      occupying a central node. Angpt-2 was strongly associated with traditional DIC
      markers including platelet counts, yet more accurately predicted mortality in 2
      large independent cohorts (combined N = 1,077). In endotoxemic mice, reduced Tie2
      signaling preceded signs of overt DIC. During this early phase, intravital
      imaging of microvascular injury revealed excessive fibrin accumulation, a pattern
      remarkably mimicked by Tie2 deficiency even without inflammation. Conversely,
      Tie2 activation normalized prothrombotic responses by inhibiting endothelial
      tissue factor and phosphatidylserine exposure. Critically, Tie2 activation had no
      adverse effects on bleeding. These results mechanistically implicate Tie2
      signaling as a central regulator of microvascular thrombus formation in septic
      DIC and indicate that circulating markers of the Tie2 axis could facilitate
      earlier diagnosis. Finally, interventions targeting Tie2 may normalize
      coagulation in inflammatory states while averting the bleeding risks of current
      DIC therapies.

PMID- 29360644
TI  - Parameters Associated With Mandibular Osteoradionecrosis.
AB  - The objective of this review is to discuss factors related to the risk of
      osteoradionecrosis (ORN) and how to minimize the likelihood of this complication.
      A PubMed search for publications pertaining to ORN within the last 3 years was
      conducted revealing 44 publications. The bibliographies of these publications
      were reviewed to identify additional references spanning a longer time period.
      The incidence of ORN is 5% to 10% with a median latency period of 1 to 2 years or
      less. The likelihood of ORN depends on a number of factors including primary site
      and extent of disease, dental status, treatment modality, radiotherapy (RT) dose,
      volume of mandible included in the planning target volume, RT fractionation
      schedule and technique, and teeth extractions. The risk of ORN may be reduced by
      limiting the RT dose and volume of mandible irradiated without increasing the
      risk of a local-regional recurrence due to a marginal miss.

PMID- 29360645
TI  - Breast Cancer Stage at Diagnosis in a New Jersey Cancer Education and Early
      Detection Site.
AB  - OBJECTIVES: The National Breast and Cervical Cancer Early Detection Program
      provides free or low-cost screening to uninsured or underinsured women and has
      had positive results; however, only a few state programs have been evaluated.
      This study will provide a first snapshot of the effectiveness of the New Jersey
      program, by comparing stage at diagnosis for enrollees as compared with
      nonenrollees who received definitive treatment for breast cancer at the same
      academic medical center. MATERIALS AND METHODS: A retrospective analysis of 5
      years of breast cancer data abstracted from the Cancer Registry of a large urban
      hospital in the Northeast United States. Bivariate analysis and logistic
      regression were utilized. RESULTS: One thousand forty women were screened for and
      diagnosed with breast cancer at this site; they were more likely to be racially
      (P<0.001) and ethnically (P<0.002) diverse as compared with nonenrollees.
      Enrollees were more likely to be symptomatic at diagnosis (P<0.001), and
      diagnosed at a late stage when compared with nonenrollees (odds ratio, 1.88; 95%
      confidence interval, 1.07-3.29). CONCLUSIONS: This national program was developed
      to serve low income, under and uninsured women who may otherwise have limited
      access to cancer screening services. It appears that many women enroll in this
      program needing diagnostic rather than screening services, after breast symptoms
      were noted. This finding helps to emphasize the fact that just providing free
      screening services is not enough to make up for the lack of a usual source of
      preventive care for low income and uninsured women.

PMID- 29360646
TI  - Effects of Cane Use and Position on Performance of the Sit-to-Stand Task in
      Stroke Patients.
AB  - OBJECTIVE: The aim of the study was to examine the effect of cane use and cane
      positions on the sit-to-stand performance of stroke patients. DESIGN: In a
      crossover study, 30 stroke patients performed sit-to-stand test in seven
      situations in a random sequence: without a cane, three positions with a regular
      cane (parallel to the ankle, parallel to the 5th toe, and 10 cm in front of the
      5th toe), and the same three positions with a quad cane. The peak vertical ground
      reaction force and maximum vertical cane support force during sit-to-stand were
      recorded. RESULTS: Using a cane significantly reduced the peak ground reaction
      force by 3% to 9% of body weight compared with that without a cane (P = 0.000
      0.023). Different cane positions strongly influenced the maximum cane support
      force and peak ground reaction force. When the cane was closer to the ankle, the
      maximal cane support force increased by 6.7% to 8.6% of body weight, which
      resulted in a decrease in the peak ground reaction force. CONCLUSIONS: Both types
      of cane reduced lower limbs' load during sit to stand. When the cane was closer
      to the trunk, the load on legs was lessened, whereas the load on the upper limb
      increased. Upper limb's load during sit to stand was greater when using quad cane
      than using regular cane.

PMID- 29360647
TI  - Premorbid Activity Limitation Stages Are Associated With Posthospitalization
      Discharge Disposition.
AB  - OBJECTIVE: Activity of daily living stages and instrumental activity of daily
      living stage have demonstrated associations with mortality and health service use
      among older adults. This cohort study aims to assess the associations of
      premorbid activity limitation stages with acute hospital discharge disposition
      among community-dwelling older adults. DESIGN: Study participants were Medicare
      beneficiaries aged 65 yrs or older who enrolled in the Medicare Current
      Beneficiary Survey between 2001 and 2009. Associations of premorbid stages with
      discharge dispositions were estimated with multinomial logistic regression models
      adjusted for covariates. RESULTS: The proportions of elderly Medicare patients
      discharged to home with self-care, home with services, postacute care facilities,
      and other dispositions were 59%, 15%, 19%, and 7%, respectively. The following
      adjusted relative risk ratios and 95% confidence intervals of postacute care
      facilities versus home with self-care discharge increased with higher premorbid
      activity limitation stages (except nonfitting stage III): 1.7 (1.5-2.0), 2.4 (2.0
      2.9), 2.4 (1.9-3.0), and 2.5 (1.6-4.1) for activity of daily living stages I-IV;
      a similar pattern was found for instrumental activity of daily living stages. The
      adjusted relative risk ratios of discharge to home with services also increased
      with higher premorbid activity limitation stages compared with no limitation.
      CONCLUSIONS: Routinely assessed activity limitation stages predict
      posthospitalization discharge disposition among older adults and may be used to
      anticipate postacute care and services use by elderly Medicare beneficiaries.

PMID- 29360648
TI  - Artificial intelligence estimates the impact of human papillomavirus types in
      influencing the risk of cervical dysplasia recurrence: progress toward a more
      personalized approach.
AB  - The objective of this study was to determine whether the pretreatment human
      papillomavirus (HPV) genotype might predict the risk of cervical dysplasia
      persistence/recurrence. Retrospective analysis of prospectively collected data of
      consecutive 5104 women who underwent the HPV-DNA test were matched with
      retrospective data of women undergoing either follow-up or medical/surgical
      treatment(s) for genital HPV-related infection(s). Artificial neuronal network
      (ANN) analysis was used in order to weight the importance of different HPV
      genotypes in predicting cervical dysplasia persistence/recurrence. ANN simulates
      a biological neuronal system from both the structural and functional points of
      view: like neurons, ANN acquires knowledge through a learning-phase process and
      allows weighting the importance of covariates, thus establishing how much a
      variable influences a multifactor phenomenon. Overall, 5104 women were tested for
      HPV. Among them, 1273 (25%) patients underwent treatment for HPV-related
      disorders. LASER conization and cervical vaporization were performed in 807 (59%)
      and 386 (30%) patients, respectively, and secondary cervical conization in 45
      (5.5%). ANN technology showed that the most important genotypes predicting
      cervical dysplasia persistence/recurrence were HPV-16 (normalized importance:
      100%), HPV-59 (normalized importance: 51.2%), HPV-52 (normalized importance:
      47.7%), HPV-18 (normalized importance: 32.8%) and HPV-45 (normalized importance:
      30.2%). The pretreatment diagnosis of all of those genotypes, except HPV-45,
      correlated with an increased risk of cervical dysplasia persistence/recurrence;
      the pretreatment diagnosis was also arrived at using standard univariate and
      multivariable models (P<0.01). Pretreatment positivity for HPV-16, HPV-18, HPV-52
      and HPV-59 might correlate with an increased risk of cervical dysplasia
      persistence/recurrence after treatment. These data might be helpful during
      patients' counseling and to implement new vaccination programs.

PMID- 29360649
TI  - A cross-sectional analysis of ex-smokers and characteristics associated with
      quitting smoking: The Polish Norwegian Study (PONS).
AB  - Tobacco smoking remains a number one preventable risk factor of premature death
      worldwide. Findings of recent research show concurrent trends of lung cancer
      deaths in males and females in Europe. Although lung cancer death rates are
      consistently decreasing in male population, in women an upward trend is observed.
      The burden of tobacco-related harm can be prevented by smoking cessation. The
      main goal of this analysis is to identify the crucial correlates of successful
      smoking cessation in the middle-aged Polish population. The data came from 13 172
      survey participants south-eastern part of Poland as part of the PONS cohort study
      established in 2010. A total of 6998 records of those who were either ex-smokers
      or current smokers at baseline were analyzed. We applied logistic regression and
      adjusted for sociodemographic covariates and health determinants. Characteristics
      related to being an ex-smoker as opposed to a current smoker included: older age
      [men: odds ratio (OR)=1.03, 95% confidence interval (CI)=1.01-1.05; women:
      OR=1.05, 95% CI=1.03-1.07], being married or living together, having secondary
      (OR=1.51, 95% CI=1.14-1.99) or higher (OR=2.30, 95% CI=1.75-3.18) education
      (women), full-time employment (men), alcohol consumer (women), being overweight
      (men: OR=2.85, 95% CI=2.26-3.59; women: OR=1.60, 95% CI=1.36-1.87) or obese (men:
      OR=3.47, 95% CI=2.67-4.51; women: OR=2.99, 95% CI=2.45-3.65), having normal
      fasting glucose and cholesterol blood level without any treatment (women),
      assessing their own health highly (9-10, on the scale from 1 to 10) and having at
      least one accompanying chronic disease (women, OR=1.25, 95% CI=1.07-1.45). These
      findings provide valuable information on characteristics of ex-smokers as well as
      behavioral and sociodemographic predictors of successful cessation. Such data
      expand our knowledge and can be used to design a more comprehensive and targeted
      group-specific tobacco control policy focused on increasing the number of ex
      smokers.

PMID- 29360651
TI  - Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 2:
      Optimizing the Design of Human Abuse Potential Studies.
AB  - PURPOSE: This article discusses the conduct of a human abuse potential study as
      outlined in the Food and Drug Administration Final Guidance to Industry on
      Assessment of Abuse Potential. In addition, areas where alternative approaches
      should be considered are proposed. PROCEDURES: The design, end points, conduct,
      and interpretation of the human abuse potential study were reviewed, analyzed,
      and placed in the context of current scientific knowledge and best practices to
      mitigate regulatory risk and expedite drug development. FINDINGS: The guidance is
      based on regulatory needs and current scientific practices. However, the
      reliability and utility of such studies can be improved with better subject
      selection, data collection, standardization of data collection and staff
      training, and a better understanding of the measurement properties of the
      dependent measures. CONCLUSIONS: The guidance provides a useful framework for
      conduct of human abuse potential studies. However, design assumptions, poor
      choice of end points, failure to consider alternate approaches, and limited
      experience with interpretation can result in an inadequate study or one that does
      not fairly represent the abuse potential of a new chemical entity. Methodologic
      development is needed to strengthen the regulatory framework. The Food and Drug
      Administration or the National Institutes on Drug Abuse could take a targeted
      initiative to encourage this work.

PMID- 29360650
TI  - Exploring Nitrous Oxide as Treatment of Mood Disorders: Basic Concepts.
AB  - Nitrous oxide (laughing gas) has shown early promise as a rapidly acting
      antidepressant in patients with treatment-resistant major depression and is
      currently investigated in several clinical trials. Because nitrous oxide is
      rarely administered outside operating rooms or dental practices, most
      psychiatrists are not familiar with how nitrous oxide is administered in a
      medical setting and what regulations guide its use. The goal of this brief review
      was to educate psychiatrists about the basic concepts of nitrous oxide
      administration and pharmacology. Furthermore, common misconceptions about nitrous
      oxide will be discussed.

PMID- 29360652
TI  - Hyperprolactinemic Galactorrhea as a Side Effect of Aripiprazole: An Adolescent
      Case (Aripiprazole-Related Hyperprolactinemic Galactorrhea).

PMID- 29360653
TI  - Regional Dermabrasion of Nasal Surgical Scars and Rhinophyma Using Electrocautery
      Scratch Pads.

PMID- 29360655
TI  - Hypertrophic Lichen Planus and Well-Differentiated Squamous Cell Carcinoma: A
      Diagnostic Conundrum.

PMID- 29360654
TI  - Commentary on Punctuated 88% Phenol Peeling for the Treatment of Facial
      Photoaging.

PMID- 29360656
TI  - Retrospective Multistudy Analysis of Axillary Odor Reduction After Microwave
      Treatment.

PMID- 29360657
TI  - Combination of Melolabial Interpolation Flap and Nasal Sidewall and Cheek
      Advancement Flaps Allows for Repair of Complex Compound Defects.
AB  - BACKGROUND: The paramedian forehead flap (PMFF) is the repair of choice for large
      nasal defects involving multiple cosmetic subunits. However, the PMFF may not be
      optimal for all patients. The combination of a melolabial interpolation flap
      (MLIF) and a nasal sidewall flap may serve as an alternative. OBJECTIVE: To
      present the surgical technique and aesthetic outcomes of the alternative
      reconstruction for surgical defects of the lower nose. MATERIALS AND METHODS:
      Fourteen patients with multisubunit nasal Mohs defects reconstructed
      alternatively were identified from 2 academic centers in this retrospective case
      series. Illustrations and photographs were used to demonstrate surgical technique
      and outcomes. Final aesthetic results were analyzed using the Patient and
      Observer Scar Assessment Scale. RESULTS: The physician observer rated the scar
      outcome a mean score of 10.9 +/- 3.3. Patients rated their results as a mean of
      9.1 +/- 4.7. The mean "Patient" Overall Opinion score was 2.3 +/- 2.6 and the
      mean "Observer" Overall Opinion score was 1.9 +/- 0.9. No patients reported
      problems with nasal airflow or obstruction, and cosmetic complications such as
      pincushioning or alar buckling were not observed. CONCLUSION: The combined MLIF
      and nasal sidewall flap is an alternative repair for complex distal nasal
      defects.

PMID- 29360659
TI  - High Risk of Mismatch Between Sanders and Risser Staging in Adolescent Idiopathic
      Scoliosis: Are We Guiding Treatment Using the Wrong Classification?
AB  - BACKGROUND: Despite known limitations, Risser staging has traditionally been the
      primary marker of skeletal maturity utilized in decision-making for treatment of
      adolescent idiopathic scoliosis (AIS). The purpose of this study is to assess the
      incidence and factors associated with mismatch between Risser Staging and Sanders
      classification, and determine interobserver reliability. METHODS: We reviewed the
      medical records of consecutive patients aged 10 to 18 referred to our institution
      for evaluation of AIS from January to June 2016 with a closed triradiate
      cartilage. Data collected included sex, age, race, height, weight, body mass
      index percentile, menarchal status, Risser stage, Sanders classification, and
      major curve. Risser and Sanders stage was determined by 2 fellowship-trained
      pediatric spine surgeons and 1 pediatric orthopaedic nurse practitioner. Mismatch
      was defined as Risser stage 2 to 4 corresponding to Sanders 3 to 5, and Risser 0
      to 1 corresponding to Sanders 6 to 7. RESULTS: A total of 165 consecutive
      patients were identified (mean age: 13.9+/-1.7 y, major curve 28.2+/-15.4
      degrees, 76% female). The risk of skeletal maturity mismatch, based on the
      criteria of Risser 2 to 5 (limited growth remaining) corresponding to Sanders 3
      to 5 (significant growth remaining) was 21.8%, indicating that 1 of 5 patients
      would be undertreated if managed by Risser criteria. Conversely, the mismatch
      risk for Risser 0 to 1 corresponding to Sanders 6 to 7 was 3.6%, leading such
      patients to be treated conservatively longer than necessary. Males and those of
      Hispanic ethnicity were at a higher risk of mismatch (23.1% vs. 11.9%, P=0.08;
      33.3% vs. 8.8%, P=0.04, respectively). Body mass index percentile, race, and
      major curve were not associated with mismatch. The unweighted and weighted
      interobserver kappa for Risser staging was 0.74 and 0.82, respectively, and 0.86
      and 0.91 for Sanders classification, respectively. CONCLUSION: Given the limited
      sensitivity of Risser staging during peak growth velocity, high mismatch risk,
      and lower interobserver reliability, the Sanders classification should be
      utilized to guide treatment options in patients with AIS. Compared with Sanders,
      utilizing Risser staging results in mistreatment in a total of 1 of 4 patients,
      with the vast majority being undertreated. LEVEL OF EVIDENCE: Level II.

PMID- 29360658
TI  - Hyaluronic Acid Filler Injections Under the Metatarsal Heads Provide a
      Significant and Long-Lasting Improvement in Metatarsalgia From Wearing High
      Heeled Shoes.
AB  - BACKGROUND: Metatarsalgia is a common overuse injury that may be caused by
      wearing high-heeled shoes. OBJECTIVE: To evaluate the decrease in metatarsalgia
      using a hyaluronic acid dermal filler. METHODS: A 6-month, open study was
      conducted in 15 subjects with metatarsalgia because of regularly wearing high
      heeled shoes. Hyaluronic acid (20 mg/mL) with lidocaine hydrochloride (3 mg/mL)
      was injected under the metatarsal heads at baseline. Pain (on a 0-10 scale) under
      the metatarsal heads when walking in high heels was recorded in a weekly subject
      diary. RESULTS: At 6 months after injections, 5 subjects (33.3%) reported no
      metatarsalgia pain. For subjects with pain, they were able to wear high heels for
      significantly longer than before the injections (7.2 hours at 6 months vs 3.4
      hours at baseline). Significant improvements from baseline were observed at Month
      6 for time to onset of pain (3.5 hours longer), time between onset of pain and
      intolerable pain (1.9 hours longer), and pain sensation (-2.2 grades at onset and
      -3.8 grades at shoe removal). No adverse events were reported. CONCLUSION:
      Injection of hyaluronic acid filler to the forefeet provided a significant
      effective, long-lasting, and well-tolerated improvement in metatarsalgia because
      of wearing high-heeled shoes.

PMID- 29360660
TI  - Relationships Between the Axial Derotation of the Lower Instrumented Vertebra and
      Uninstrumented Lumbar Curve Correction: Radiographic Outcome in Lenke 1
      Adolescent Idiopathic Scoliosis With a Minimum 2-Year Follow-up.
AB  - BACKGROUND: Preoperative spinal parameters are used to guide the fusion levels in
      adolescent idiopathic scoliosis (AIS) spinal surgery. However, the impact of the
      factors modifiable by the surgeon in varying levels of preoperative patient
      specific variables is not fully explored. The goal of this study was to identify
      the association between axial rotation correction of the lower instrumented
      vertebra (LIV) and spontaneous correction of the uninstrumented lumbar spine as a
      function of preoperative 3 dimensional (3D) curve characteristics in Lenke 1 AIS.
      METHODS: Twenty-three Lenke1 AIS with a minimum 2-year follow-up were included.
      All patients had biplanar spinal x-rays and 3D reconstructions at preoperative,
      first erect, and 2-year follow-up visits. Five patient factors were measured
      preoperatively: kyphosis and lumbar modifiers, and thoracic to lumbar curve
      rotation, translation, and frontal deformity angle ratios. One surgical factor,
      percentage of LIV rotation correction, was determined from the preoperative and
      first erect 3D models. A factorial design analysis was implemented to determine
      the impact of surgical and patient factors, both separately and in combination,
      on 2-year radiographic outcomes of spontaneous correction of the uninstrumented
      spine. RESULTS: Spontaneous lumbar Cobb and lumbar apical rotation correction
      were predicted significantly by patient and surgical factors, P<0.05. Lumbar
      modifier, percentage correction of LIV rotation, the interaction between LIV
      rotation correction and lumbar modifier, and the interaction between LIV rotation
      correction and thoracic to lumbar apical vertebrae translation ratio correlated
      significantly to 2-year outcomes of spontaneous lumbar Cobb correction, P<0.05.
      Lumbar modifier and the interaction between the Cobb ratio and the percentage of
      the LIV rotation correction correlated significantly to 2-year outcomes of lumbar
      apical rotation correction, P<0.05. CONCLUSION: The relationship between LIV
      rotation correction and spontaneous lumbar curve correction after selective
      thoracic fusion varied based on the patient's 3D preoperative curve
      characteristics. Patients with lumbar modifier C and apical vertebrae translation
      ratios >1.5 showed improved lumbar Cobb correction in 2-years when 50% or more
      LIV rotation correction was achieved surgically.

PMID- 29360661
TI  - Palbociclib has no clinically relevant effect on the QTc interval in patients
      with advanced breast cancer.
AB  - The aim of this study was to assess the potential effects of palbociclib in
      combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind,
      placebo-controlled trial, compared palbociclib plus letrozole with placebo plus
      letrozole in postmenopausal women with estrogen receptor-positive, human
      epidermal growth factor receptor 2-negative advanced breast cancer. The study
      included a QTc evaluation substudy carried out as a definitive QT interval
      prolongation assessment for palbociclib. Time-matched triplicate ECGs were
      performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14.
      Additional ECGs were collected from all patients for safety monitoring. The QT
      interval was corrected for heart rate using Fridericia's correction (QTcF),
      Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In
      total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or
      placebo plus letrozole. Of these, 125 patients were enrolled in the QTc
      evaluation substudy. No patients in the palbociclib plus letrozole arm of the
      substudy (N=77) had a maximum postbaseline QTcS or QTcF value of >= 480 ms, or a
      maximum increase from clock time-matched baseline for QTcS or QTcF values of >=
      60 ms. The upper bounds of the one-sided 95% confidence interval for the mean
      change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and
      at steady-state Cmax following repeated administration of 125 mg palbociclib were
      less than 10 ms. Palbociclib, when administered with letrozole at the recommended
      therapeutic dosing regimen, did not prolong the QT interval to a clinically
      relevant extent.

PMID- 29360663
TI  - Kinetic Asymmetry during Running at Preferred and Nonpreferred Speeds.
AB  - PURPOSE: The aim of this study was to investigate the effect of altering
      preferred running speed by +/-20% on kinetic asymmetry. METHODS: Three
      dimensional motion analysis and force data were acquired from 15 healthy males
      (age, 27 +/- 4.6 yr; height, 1.81 +/- 0.09 m; mass, 80.4 +/- 12.4 kg) during
      their preferred running speed and at +/-20% of this speed. Three-tesla magnetic
      resonance images were used to measure Achilles tendon cross-sectional area and
      moment arm, for use in calculation of tendon stress. Kinetic and tendon stress
      asymmetry were subsequently calculated in each condition using the symmetry
      index. RESULTS: Across all joints and conditions, the average asymmetry of peak
      moments was between +/-6%, but higher individual values were observed. There was
      no effect of speed on the magnitude of asymmetry. Ground contact times, vertical
      ground reaction forces, and support and ankle moments (maximum absolute
      asymmetry, 9%) were more symmetrical than hip and knee moments (up to 18%).
      Individual joint contribution to support moment and positive work were similar in
      both limbs, and ankle and hip compensatory interactions were observed with
      alterations in running speed. Achilles tendon stress increased with increased
      running speed, with higher stress in the preferred limb; asymmetry in tendon
      stress was not related to asymmetry in vertical ground reaction forces.
      CONCLUSION: Results show small effects of altering running speed on kinetic
      asymmetry, but responses are individual specific with interactions occurring
      between joints to maintain overall movement symmetry. Further research is needed
      to understand the mechanical and neuromuscular mechanisms underpinning these
      compensations.

PMID- 29360662
TI  - FoxM1 promotes epithelial-mesenchymal transition, invasion, and migration of
      tongue squamous cell carcinoma cells through a c-Met/AKT-dependent positive
      feedback loop.
AB  - Forkhead box protein M1 (FoxM1) has been associated with cancer progression and
      metastasis. However, the function of FoxM1 in tongue squamous cell carcinoma
      (TSCC) remains largely unknown. The purpose of this study was to determine the
      role of FoxM1 in regulation of epithelial-mesenchymal transition (EMT) and
      migration of TSCC cells. We found that FoxM1 induced EMT and increased
      invasion/migration capacity in SCC9 and SCC25 cells. FoxM1 stimulation increased
      c-Met, pAKT, and vimentin levels but decreased E-cadherin level. Chromatin
      immunoprecipitation assay established that FoxM1 is bound to the promoter of c
      Met to activate its transcription. In turn, c-Met promoted the expression of
      FoxM1 and pAKT. Blocking AKT signaling attenuated the invasion and migration of
      SCC9 and SCC25 cells stimulated by FoxM1 or c-Met. These results indicate that a
      positive feedback loop controls the EMT and migration of TSCC cells induced by
      FoxM1 and c-Met through AKT. Furthermore, the expression levels of FoxM1, pAKT,
      and c-Met were found to significantly increase in TSCC tissues compared with
      normal tissues, and these three biomarkers were concomitantly expressed in TSCC
      tissues. Clinical association analyses indicated that the expression of FoxM1, c
      Met, and pAKT was associated with clinicopathological characteristics of patients
      with TSCC including tumor stage, tumor size, and lymph node metastasis. Taken
      together, our findings suggest that FoxM1 promotes the EMT, invasion and
      migration of TSCC cells, and cross-talks with c-Met/AKT signaling to form a
      positive feedback loop to promote TSCC development.

PMID- 29360664
TI  - Beyond Cut Points: Accelerometer Metrics that Capture the Physical Activity
      Profile.
AB  - PURPOSE: Commonly used physical activity metrics tell us little about the
      intensity distribution across the activity profile. The purpose of this paper is
      to introduce a metric, the intensity gradient, which can be used in combination
      with average acceleration (overall activity level) to fully describe the activity
      profile. METHODS: A total of 1669 adolescent girls (sample 1) and 295 adults with
      type 2 diabetes (sample 2) wore a GENEActiv accelerometer on their nondominant
      wrist for up to 7 d. Body mass index and percent body fat were assessed in both
      samples and physical function (grip strength, Short Physical Performance Battery,
      and sit-to-stand repetitions) in sample 2. Physical activity metrics were as
      follows: average acceleration (AccelAV); the intensity gradient (IntensityGRAD
      from the log-log regression line: 25-mg intensity bins [x]/time accumulated in
      each bin [y]); total moderate-to-vigorous physical activity (MVPA); and bouted
      MVPA (sample 2 only). RESULTS: Correlations between AccelAV and IntensityGRAD (r
      = 0.39-0.51) were similar to correlations between AccelAV and bouted MVPA (r =
      0.48) and substantially lower than between AccelAV and total MVPA (r >= 0.93).
      IntensityGRAD was negatively associated with body fatness in sample 1 (P < 0.05)
      and positively associated with physical function in sample 2 (P < 0.05);
      associations were independent of AccelAV and potential covariates. By contrast,
      MVPA was not independently associated with body fatness or physical function.
      CONCLUSION: AccelAV and IntensityGRAD provide a complementary description of a
      person's activity profile, each explaining unique variance, and independently
      associated with body fatness and/or physical function. Both metrics are
      appropriate for reporting as standardized measures and suitable for comparison
      across studies using raw acceleration accelerometers. Concurrent use will
      facilitate investigation of the relative importance of intensity and volume of
      activity for a given outcome.

PMID- 29360665
TI  - Corticosteroids in Pediatric Septic Shock Are Helpful.

PMID- 29360666
TI  - Specific Donor HLA-DR Types Correlate With Altered Susceptibility to Development
      of Chronic Lung Allograft Dysfunction.
AB  - BACKGROUND: The greatest challenge to long-term graft survival is the development
      of chronic lung allograft dysfunction. Th17 responses to collagen type V (colV)
      predispose lung transplant patients to the severe obstructive form of chronic
      lung allograft dysfunction, known as bronchiolitis obliterans syndrome (BOS). In
      a previous study cohort (n = 54), pretransplant colV responses were increased in
      recipients expressing HLA-DR15, consistent with the high binding avidity of colV
      (alpha1) peptides for HLA-DR15, whereas BOS incidence, which was known to be
      strongly associated with posttransplant autoimmunity to colV, was higher in
      patients who themselves lacked HLA-DR15, but whose lung donor expressed it.
      METHODS: To determine if this DR-restricted effect on BOS incidence could be
      validated in a larger cohort, we performed a retrospective analysis of outcomes
      for 351 lung transplant recipients transplanted between 1988 and 2008 at the
      University of Wisconsin. All subjects were followed until graft loss, death, loss
      to follow-up, or through 2014, with an average follow-up of 7 years. Comparisons
      were made between recipients who did or did not develop BOS. Grading of BOS
      followed the recommendations of the international society for heart and lung
      transplantation. RESULTS: Donor HLA-DR15 was indeed associated with increased
      susceptibility to severe BOS in this population. We also discovered that HLA-DR7
      expression by the donor or HLA-DR17 expression by the recipient decreased
      susceptibility. CONCLUSIONS: We show in this retrospective study that specific
      donor HLA class II types are important in lung transplantation, because they are
      associated with either protection from or susceptibility to development of severe
      BOS.

PMID- 29360667
TI  - The Influence of Environmental Enrichment on Cardiovascular and Behavioral
      Responses to Social Stress.
AB  - OBJECTIVE: Stress is linked to negative cardiovascular consequences and increases
      in depressive behaviors. Environmental enrichment (EE) involves exposure to novel
      items that provide physical and cognitive stimulation. EE has behavioral,
      cognitive, and neurobiological effects that may improve stress responses in
      humans and animal models. This study investigated the potential protective
      effects of EE on behavior and cardiovascular function in female prairie voles
      after a social stressor. METHODS: Radiotelemetry transmitters were implanted into
      female prairie voles to measure heart rate (HR) and heart rate variability (HRV)
      throughout the study. All females were paired with a male partner for 5 days,
      followed by separation from their partner for 5 additional days, and a 10-day
      treatment period. Treatment consisted of continued isolation, isolation with EE,
      or re-pairing with the partner (n = 9 per group). After treatment, animals were
      observed in the forced swim test (FST) for measures of stress coping behaviors.
      RESULTS: Isolation elevated HR and reduced HRV relative to baseline for all
      groups (p < .001). HR and HRV returned to baseline in the EE and re-paired
      groups, but not in the continued isolation group (p < .001). Animals in the EE
      and re-paired groups displayed significantly lower immobility time (p < .001) and
      HR (p < .03) during the FST, with a shorter latency for HR to return to baseline
      levels after the FST, relative to the continued isolation group (p < .001).
      CONCLUSIONS: EE and re-pairing reversed the negative behavioral and
      cardiovascular consequences associated with social isolation.

PMID- 29360668
TI  - Your Anesthesiologist Self.

PMID- 29360669
TI  - Complications Following Arthroscopic Rotator Cuff Repair and Reconstruction.

PMID- 29360670
TI  - Not All Polyaxial Locking Screw Technologies Are Created Equal: A Systematic
      Review of the Literature.
AB  - BACKGROUND: Locking plate fixation strength relies on axial alignment of the
      screw axis and plate hole, with small deviations in alignment substantially
      decreasing the load to failure. In an effort to overcome this technical
      deficiency, polyaxial locking plates were designed to provide increased
      flexibility of screw positioning with the intent of not sacrificing fixation
      strength. The purpose of this article is to review the variety of polyaxial
      locking mechanisms currently available, to compare the biomechanical performance
      of these designs, and to highlight their differences, which may have clinical
      implications. METHODS: A systematic review using the search terms "polyaxial
      locking," "variable angle locking," "polyaxial screws," and "variable angle
      screws" was conducted to identify all English-language articles assessing
      variable-angle locking screw technology. All articles directly comparing the
      biomechanical performance of polyaxial locking technologies were included.
      RESULTS: Polyaxial locking is achieved by 5 described mechanisms: point-loading
      thread-in, cut-in, locking cap, expansion bushing, and screw-head expansion. With
      increasing insertion angulation, point-loading thread-in and cut-in designs
      demonstrate reduced failure strength. However, locking-cap fixation maintains
      consistent failure strength with increasing off-axis insertion angles.
      CONCLUSIONS: Reports comparing polyaxial locking technologies are limited. The
      current biomechanical literature raises concerns that these mechanisms have
      various strengths and performance characteristics. Based on the results of the
      few studies that exist, it appears that locking-cap fixation provides superior
      biomechanical strength when compared with point-loading and cut-in designs.
      Additional studies are needed to assess variable-angle locking mechanisms more
      completely.

PMID- 29360671
TI  - Neonatal Abstinence Syndrome: Exploring Nurses' Attitudes, Knowledge, and
      Practice.
AB  - BACKGROUND: As opioid abuse increases in the United States, the rate of neonatal
      abstinence syndrome (NAS) rises dramatically. Caring for infants with NAS and
      their families is a significant challenge to neonatal nurses. PURPOSE: The
      purpose of this survey study was to explore attitudes and practice trends among
      nurses caring for infants with NAS. The study also aimed to identify any gaps in
      knowledge about NAS. METHOD: An anonymous, cross-sectional survey study was
      conducted using a researcher-developed questionnaire. The survey questionnaire
      included 20 Likert-scale questions regarding nurses' attitudes, knowledge, and
      practice in care of infants with NAS, 1 case study with 3 questions, and 2 open
      ended questions. Nurses, including advanced practice nurses and nurse leaders,
      were invited to participate at a regional neonatal nursing conference in the New
      England area. RESULTS: A total of 54 participants responded, the majority being
      white, female, non-Hispanic, and bachelor's prepared. Many nurses shared concerns
      regarding the setting in which infants with NAS are cared for. Nurses expressed
      varying attitudes regarding interacting with the mothers but generally wanted to
      build a partnership with them. Nurses also reported a lack of standardized and
      consistent practice in care for infants with NAS. Three major themes were
      identified from open-ended questions, including environmental issues,
      relationship with the mother, and inconsistency in care. IMPLICATIONS FOR
      PRACTICE: Further research is needed for nurses providing care to infants with
      NAS. Specific education programs are needed for nurses who are caring for infants
      with NAS. IMPLICATIONS FOR RESEARCH: Further research is needed regarding the
      effects of NAS on nurses and other healthcare providers.

PMID- 29360672
TI  - Effects of a Psychoeducational Intervention in Patients With Breast Cancer
      Undergoing Chemotherapy.
AB  - BACKGROUND: Compelling evidence has yet to be published regarding the positive
      effect of psychoeducational interventions (PEIs) on psychological distress in
      patients with breast cancer. The impact of PEIs on self-efficacy, resilience, and
      quality of life is also unclear. PURPOSE: The aim of this study was to assess the
      effects of a PEI on anxiety, depression, disease-specific care knowledge, self
      efficacy, resilience and quality of life in patients with breast cancer during
      and after chemotherapy. The intervention was administered before and during five
      rounds of chemotherapy treatment. METHODS: A randomized controlled trial was
      conducted. Patients with breast cancer (N = 40) were randomly assigned to either
      the experimental or control group. The experimental group participated in PEI, a
      brief and highly structured program consisting of two parts: (a) an educational
      manual that addressed depression, anxiety, disease-specific care knowledge, self
      efficacy, and resilience and (b) a self-assessment of learning. The control group
      received only traditional pamphlet education. Data were collected at four time
      points: before the first chemotherapy session (T1), during the third chemotherapy
      session (T2), during the fifth chemotherapy session (T3), and at 2 weeks after
      the final chemotherapy session (T4). RESULTS: Anxiety, depression, resilience,
      and quality of life in the experimental group showed significant differences at
      T4. Significant differences became apparent at T2 for knowledge and at T3 for
      self-efficacy. The effects of knowledge, resilience, and quality of life remained
      significant when group and time interactions were included in the model, showing
      a positive relationship between PEI and the variables of knowledge, resilience,
      and quality of life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Face-to-face PEI for
      patients with breast cancer is potentially effective in improving knowledge,
      resilience, and quality of life during and after chemotherapy. In the current
      study, PEI significantly improved disease care techniques, reduced chemotherapy
      related discomfort, and improved quality of life for participants in the
      experimental group.

PMID- 29360673
TI  - The Weakest Point of "The Shepherd's Crook" Technique: Suture Tension.

PMID- 29360675
TI  - Validation of a Falls Risk Screening Tool Derived From InterRAI Acute Care
      Assessment.
AB  - OBJECTIVES: This study aimed to develop and validate a falls risk screening tool
      derived from interRAI Acute Care (AC) Assessment. METHODS: For derivation and
      validation, two prospective cohorts were recruited from AC hospitals in
      Australia. The derivation cohort comprised 1418 patients from 11 hospitals. In
      the validation cohort, 393 patients were recruited from four hospitals. The
      interRAI AC tool was used to collect comprehensive geriatric assessment data at
      admission. In-hospital falls were documented from medical records. A falls risk
      score was calculated using logistic regression. Predictive ability was compared
      with St. Thomas Risk Assessment Tool In Falling elderlY (STRATIFY), using area
      under curve (AUC). The validation cohort provided external validity. RESULTS:
      Complete data in the derivation cohort were available for 1288 patients (91%),
      with 75 (5.8%) having an in-hospital fall. The derived interRAI AC falls risk
      score (range = 0-6) had significantly better predictive ability (AUC = 0.70, 95%
      confidence interval [CI] = 0.63-0.76) compared with St. Thomas Risk Assessment
      Tool In Falling elderlY (AUC = 0.64, 95% CI = 0.58-0.70) (P = 0.033). At a cut
      point of three, 54 of 75 falls were correctly predicted by the falls risk score
      derived from interRAI AC (sensitivity = 0.72 [95% CI = 0.60-0.82] and specificity
      = 0.60 [95% CI = 0.57-0.62]). The falls risk score performed similarly in the
      validation cohort. CONCLUSIONS: The falls risk tool developed from interRAI AC is
      a valid measure to screen for in-hospital falls. Reduction in assessment burden
      without loss of fidelity can be achieved through integrating the risk screener
      within the interRAI hospital system, which automatically triggers protocols for
      falls prevention based on identified risk.

PMID- 29360674
TI  - Reconstruction of a Circumferential Upper Extremity Soft Tissue Defect With a
      Dermal Regeneration Template and Skin Grafting.
AB  - Extensive degloving injuries of the upper extremity are rare and pose unique
      reconstructive challenges. Circumferential loss of soft tissue coverage over the
      elbow treated by skin grafting is often complicated by elbow contracture and
      decreased range of motion, requiring secondary contracture release and free-flap
      reconstruction to restore function. As an alternative approach, we report a good
      outcome after the use of a dermal regenerative template and subsequent split
      thickness skin grafting. A 38-year-old right hand dominant man presented with
      circumferential degloving injury of the entire right upper extremity to the level
      of the chest wall after an industrial accident. An immediate right transradial
      amputation was performed and serial debridement was required to remove all
      devitalized tissue. A dermal regenerative template with subsequent split
      thickness skin grafting was used to cover the circumferential elbow soft tissue
      defect. Occupational therapy and splinting were used preoperatively and
      postoperatively to prevent contracture. However, axillary scar contracture
      release was required 4 months after injury. Six months after skin grafting, the
      patient had stable soft tissue coverage of the upper extremity. Shoulder motion
      measured 120-degree abduction and 140-degree forward flexion and elbow range of
      motion was 15 to 150 degrees. In this case, an excellent clinical outcome was
      obtained with a dermal regenerative template, aggressive wound care, and a
      multidisciplinary team approach.

PMID- 29360676
TI  - Incident Reports and Maintenance as Indicators for Technical Issues With Infusion
      Pumps in Clinical Practice.

PMID- 29360677
TI  - Asymmetries in Isometric Force-Time Characteristics Are Not Detrimental to Change
      of Direction Speed.
AB  - Dos'Santos, T, Thomas, C, Jones, PA, and Comfort, P. Asymmetries in isometric
      force-time characteristics are not detrimental to change of direction speed. J
      Strength Cond Res 32(2): 520-527, 2018-The purpose of this study was to determine
      the impact of between-limb asymmetries in isometric midthigh pull (IMTP) force
      time characteristics on change of direction speed (CODS). Twenty multisport
      collegiate athletes (mean +/- SD: age: 21.0 +/- 1.9 years; mass: 78.7 +/- 8.9 kg;
      and height: 1.77 +/- 0.04 m) performed 3 unilateral stance IMTP trials per limb
      and 3 modified 505 CODS trials each side to establish imbalances between left and
      right and dominant (D) and nondominant (ND) limbs. Limb dominance was defined as
      the limb that produced the highest isometric force-time value or faster CODS
      performance. Paired sample t-tests and Hedges g effect sizes revealed no
      significant differences in IMTP force-time characteristics and CODS performance
      between left and right limbs (p > 0.05, g <= 0.37). However, significant
      differences were observed between D and ND limbs for all IMTP force-time
      characteristics and CODS performance (p < 0.001, g = 0.39-0.73). No significant
      correlations were observed between IMTP asymmetries and CODS asymmetry (p >=
      0.380, r <= -0.35), and no significant differences were observed in CODS
      performance between athletes of lesser and greater IMTP asymmetries (p >= 0.10, g
      <= 0.76). Poor percentage agreements (40-60%) between like-for-like
      classifications of asymmetry (i.e., either both asymmetrical or both balanced)
      for CODS and IMTP force-time characteristics were demonstrated. Asymmetries in
      IMTP force-time characteristics and CODS performance were present; however,
      greater IMTP asymmetries had no detrimental impact on CODS performance and did
      not equate to greater asymmetries in CODS performance. Therefore, collegiate
      athletes with asymmetries within the range reported within this study (<=13%)
      should not experience detriments to CODS or faster performance from that limb
      during 180 degrees  turns.

PMID- 29360678
TI  - Advocating to Protect Our Nurses: Addressing Unethical Recruitment of Foreign
      Educated Nurses.
AB  - Advocacy in the nursing sector is often about advocating for patients. However,
      nurses have begun to put more effort into protecting their rights as workers.
      Advocacy on behalf of foreign-educated nurses has been a critical component of
      this advocacy. While foreign-educated nurses can make our nursing workforce
      stronger, this can only happen if they are well-treated and well-trained.
      Organizations across diverse missions and perspectives have come together to
      promote fair treatment of foreign-educated nurses, which ultimately ensures that
      all nurses are working as effectively as possible and that patients receive
      proper care. The Alliance for Ethical International Recruitment Practices' Health
      Care Code for Ethical Recruitment and Employment Practices represents a bottom-up
      agreement on which market practices constitute ethical recruitment. From a top
      down level, the World Health Organization's Code of Global Practice establishes
      obligations and reporting requirements for member states that commit to ensuring
      ethical recruitment. This combination of efforts, bolstered by strong advocacy,
      is gaining traction as nursing migration grows at the global level. The
      collaboration across diverse stakeholder groups and the combination of legal,
      voluntary, and global efforts to promote the rights of foreign-educated nurses
      provides a model to apply for advocacy in different areas.

PMID- 29360679
TI  - A Pilot Study of the Immunologic, Virologic, and Pathologic Consequences of Intra
      anal 5% Imiquimod in HIV-1-Infected Men With High-Grade Squamous Intraepithelial
      Lesions.
AB  - BACKGROUND: Imiquimod can be used to treat internal anal high-grade squamous
      intraepithelial lesions. In HIV-1-infected individuals there is a theoretical
      concern for increased HIV replication in anorectal tissue secondary to imiquimod
      induced mucosal inflammation. OBJECTIVE: The purpose of this study was to assess
      local virologic, immunologic, and pathologic effects of imiquimod treatment in
      HIV-infected individuals. DESIGN: This was a pilot study at a single academic
      center. SETTINGS: The study was conducted at the University of Pittsburgh Anal
      Dysplasia Clinic. PATIENTS: HIV-1-infected individuals with biopsy-confirmed
      internal anal high-grade squamous intraepithelial lesions were included.
      INTERVENTION: Imiquimod cream was prescribed for intra-anal use 3 times per week
      for 9 weeks. MAIN OUTCOME MEASURES: Anal human papillomavirus typing, anal and
      rectal tissue HIV-1 RNA and DNA quantification, cytokine gene expression, and
      anal histology were measured. RESULTS: Nine evaluable participants (1 participant
      was lost to follow-up) were all white men with a median age of 46 years
      (interquartile range = 12 y) and a median CD4 T-cell count of 480 cells per cubic
      millimeter (interquartile range = 835). All were taking antiretroviral therapy,
      and 7 of 9 had HIV-1 RNA <50 copies per milliliter. The median dose of imiquimod
      used was 27.0 (interquartile range = 3.5), and there was a median of 11 days
      (interquartile range = 10 d) from last dose to assessment. There was no
      progression to cancer, no significant change in the number of human
      papillomavirus types detected, and no significant change in quantifiable
      cytokines/HIV-1 RNA or DNA levels in anal or rectal tissue. Seven (35%) of 20
      high-grade lesions resolved to low-grade squamous intraepithelial lesions.
      LIMITATIONS: The study was limited by the small number of participants and
      variable time to final assessment. CONCLUSIONS: Intra-anal imiquimod showed no
      evidence of immune activation or increase in HIV-1 viral replication in anal and
      rectal tissue and confirmed efficacy for intra-anal high-grade squamous
      intraepithelial lesion treatment morbidity. See Video Abstract at
      http://links.lww.com/DCR/A498.

PMID- 29360680
TI  - Value of FDG-PET/CT Volumetry After Chemoradiotherapy in Rectal Cancer.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy followed by an optimal surgery is the
      standard treatment for patients with locally advanced rectal cancer. FDG-PET/CT
      is commonly used as the modality for assessing the effect of chemoradiotherapy.
      OBJECTIVE: The purpose of this study was to investigate whether PET/CT-based
      volumetry could contribute to the prediction of pathological complete response or
      prognosis after neoadjuvant chemoradiotherapy. DESIGN: This was a retrospective
      cohort study. SETTINGS: This study was conducted at a single research center.
      PATIENTS: Ninety-one consecutive patients with locally advanced rectal cancer
      were enrolled between January 2005 and December 2015. INTERVENTION: Patients
      underwent PET/CT before and after neoadjuvant chemoradiotherapy. MAIN OUTCOME
      MEASURES: Maximum standardized uptake value and total lesion glycolysis on PET/CT
      before and after neoadjuvant chemoradiotherapy were calculated using isocontour
      methods. Correlations between these variables and clinicopathological factors and
      prognosis were assessed. RESULTS: PET/CT-associated variables before
      chemoradiotherapy were not correlated with either clinicopathological factors or
      prognosis. Maximum standardized uptake value was associated with pathological
      complete response, but total lesion glycolysis was not. Maximum standardized
      uptake value correlated with ypT, whereas total lesion glycolysis correlated with
      both ypT and ypN. High total lesion glycolysis was associated with a considerably
      poorer prognosis; the 5-year recurrence rate was 65% and the 5-year mortality
      rate 42%, whereas in lesions with low total lesion glycolysis, these were 6% and
      2%. On multivariate analysis, high total lesion glycolysis was an independent
      risk factor for recurrence (HR = 4.718; p = 0.04). LIMITATIONS: The gain in
      fluoro-2-deoxy-D-glucose uptake may differ between scanners, thus the general
      applicability of this threshold should be validated. CONCLUSIONS: In patients
      with locally advanced rectal cancer, high total lesion glycolysis after
      neoadjuvant chemoradiotherapy is strongly associated with a worse prognosis.
      Total lesion glycolysis after chemoradiotherapy may be a promising preoperative
      predictor of recurrence and death. See Video Abstract at
      http://links.lww.com/DCR/A464.

PMID- 29360681
TI  - Superficial Acral Fibromyxoma With Cartilaginous Metaplasia.

PMID- 29360682
TI  - Ontogeny-related pharmacogene changes in the pediatric liver transcriptome.
AB  - OBJECTIVES: The majority of drug dosing studies are based on adult populations,
      with modification of the dosing for children based on size and weight. This
      rudimentary approach for drug dosing children is limited, as biologically a child
      can differ from an adult in far more aspects than just size and weight.
      Specifically, understanding the ontogeny of childhood liver development is
      critical in dosing drugs that are metabolized through the liver, as the rate of
      metabolism determines the duration and intensity of a drug's pharmacologic
      action. Therefore, we set out to determine pharmacogenes that change over
      childhood development, followed by a secondary agnostic analysis, assessing
      changes transcriptome wide. MATERIALS AND METHODS: A total of 47 human liver
      tissue samples, with between 10 and 13 samples in four age groups spanning
      childhood development, underwent pair-end sequencing. Kruskal-Wallis and
      Spearman's rank correlation tests were used to determine the association of gene
      expression levels with age. Gene set analysis based on the pathways in KEGG
      utilized the gamma method. Correction for multiple testing was completed using q
      values. RESULTS: We found evidence for increased expression of 'very important
      pharmacogenes', for example, coagulation factor V (F5) (P=6.7*10), angiotensin I
      converting enzyme (ACE) (P=6.4*10), and solute carrier family 22 member 1
      (SLC22A1) (P=7.0*10) over childhood development. In contrast, we observed a
      significant decrease in expression of two alternative CYP3A7 transcripts
      (P=1.5*10 and 3.0*10) over development. The analysis of genome-wide changes
      detected transcripts in the following genes with significant changes in mRNA
      expression (P<1*10 with false discovery rate<5*0): ADCY1, PTPRD, CNDP1, DCAF12L1
      and HIP1. Gene set analysis determined ontogeny-related transcriptomic changes in
      the renin-angiotensin pathway (P<0.002), with lower expression of the pathway, in
      general, observed in liver samples from younger participants. CONCLUSION:
      Considering that the renin-angiotensin pathway plays a central role in blood
      pressure and plasma sodium concentration, and our observation that ACE and PTPRD
      expression increased over the spectrum of childhood development, this finding
      could potentially impact the dosing of an entire class of drugs known as ACE
      inhibitors in pediatric patients.

PMID- 29360683
TI  - SHORT-TERM EFFICACY OF CONBERCEPT AND RANIBIZUMAB FOR POLYPOIDAL CHOROIDAL
      VASCULOPATHY.
AB  - PURPOSE: To compare the 6-month efficacy of the intravitreal injection of
      conbercept or ranibizumab for patients with polypoidal choroidal vasculopathy
      (PCV). METHODS: This is a retrospective case-control study involved 79 PCV eyes
      of 77 patients. The PCV eyes were treated with an intravitreal injection of
      either ranibizumab (n = 44) or conbercept (n = 35). Three monthly loading doses
      were injected and followed by retreatment as needed. The best-corrected visual
      acuity and angiographic characteristics were evaluated after 6 months. RESULTS:
      The mean logarithm of the minimum angle of resolution best-corrected visual
      acuity had improved from 0.86 (Snellen equivalent, 20/145) at baseline to 0.70
      (Snellen equivalent, 20/100) at 6 months in the conbercept group (P < 0.001), and
      from 0.74 (Snellen equivalent, 20/110) at baseline to 0.63 (Snellen equivalent,
      20/85) at 6 months in the ranibizumab group (P = 0.032), respectively. The
      central foveal thickness was decreased from 407 +/- 146 MUm to 230 +/- 71 MUm in
      the conbercept group (P < 0.001), and from 394 +/- 93 MUm to 208 +/- 56 MUm in
      the ranibizumab group (P < 0.001). Polyps were completely regressed and in 21
      (47.7%) eyes in the conbercept group at 6 months, significant higher than in 10
      (28.6%) eyes in the ranibizumab group (P = 0.029). CONCLUSION: Both conbercept
      and ranibizumab effectively increased the visual acuity and regressed the polyps
      of PCV eyes. No significant difference was found in the visual acuity improvement
      of the patients with PCV between the conbercept group and ranibizumab group at 6
      months. However, conbercept was superior to ranibizumab monotherapy in the
      regression of polyps.

PMID- 29360685
TI  - Diagnostic and Therapeutic Challenges.

PMID- 29360684
TI  - Thrombus in Lamina Cribrosa Seen Using Swept-Source Optical Coherence Tomography
      in Eye With Central Retinal Artery Occlusion.

PMID- 29360686
TI  - THREE-DIMENSIONAL ANALYSIS OF RETINAL MICROANEURYSMS WITH ADAPTIVE OPTICS OPTICAL
      COHERENCE TOMOGRAPHY.
AB  - PURPOSE: To characterize retinal microaneurysms (MAs) in patients with diabetes
      using adaptive optics optical coherence tomography (AOOCT) and compare details
      found in AOOCT with those found in commercially available retinal imaging
      techniques. METHODS: Patients with diabetes and MA in the macular area were
      included in this pilot study. The area of interest, identified in standard
      fluorescein angiography, was imaged using an AO fundus camera and AOOCT.
      Microaneurysms were characterized in AOOCT (visibility, reflectivity,
      feeding/draining vessels, and intraretinal location) and compared with findings
      in AO fundus camera, OCT angiography, and fluorescein angiography. RESULTS: Fifty
      three MAs were imaged in 15 eyes of 10 patients. Feeding and/or draining vessels
      from both capillary plexus could be identified in 34 MAs in AOOCT images. Of 45
      MAs imaged with OCT angiography, 18 (40%) were visible in the superior plexus, 12
      (27%) in the deep capillary plexus, and 15 MAs (33%) could not be identified at
      all. Intraluminal hyperreflectivity, commonly seen in AO fundus camera,
      corresponded only in 8 of 27 cases (30%) to intraluminal densities seen in AOOCT.
      CONCLUSION: Adaptive optics OCT imaging revealed that MAs located in the inner
      nuclear layer were connected to the intermediate and/or deep capillary plexus.
      Intraluminal hyperreflectivity seen on AO fundus camera images originated from a
      strong reflection from the vessel wall and only in a third of the cases from
      intraluminal clots. Currently, AOOCT is the most expedient in vivo imaging method
      to capture morphologic details of retinal microvasculature in 3D and in the
      context of the surrounding retinal anatomy.

PMID- 29360687
TI  - Deep Learning-Based Noise Reduction Approach to Improve Speech Intelligibility
      for Cochlear Implant Recipients.
AB  - OBJECTIVE: We investigate the clinical effectiveness of a novel deep learning
      based noise reduction (NR) approach under noisy conditions with challenging noise
      types at low signal to noise ratio (SNR) levels for Mandarin-speaking cochlear
      implant (CI) recipients. DESIGN: The deep learning-based NR approach used in this
      study consists of two modules: noise classifier (NC) and deep denoising
      autoencoder (DDAE), thus termed (NC + DDAE). In a series of comprehensive
      experiments, we conduct qualitative and quantitative analyses on the NC module
      and the overall NC + DDAE approach. Moreover, we evaluate the speech recognition
      performance of the NC + DDAE NR and classical single-microphone NR approaches for
      Mandarin-speaking CI recipients under different noisy conditions. The testing set
      contains Mandarin sentences corrupted by two types of maskers, two-talker babble
      noise, and a construction jackhammer noise, at 0 and 5 dB SNR levels. Two
      conventional NR techniques and the proposed deep learning-based approach are used
      to process the noisy utterances. We qualitatively compare the NR approaches by
      the amplitude envelope and spectrogram plots of the processed utterances.
      Quantitative objective measures include (1) normalized covariance measure to test
      the intelligibility of the utterances processed by each of the NR approaches; and
      (2) speech recognition tests conducted by nine Mandarin-speaking CI recipients.
      These nine CI recipients use their own clinical speech processors during testing.
      RESULTS: The experimental results of objective evaluation and listening test
      indicate that under challenging listening conditions, the proposed NC + DDAE NR
      approach yields higher intelligibility scores than the two compared classical NR
      techniques, under both matched and mismatched training-testing conditions.
      CONCLUSIONS: When compared to the two well-known conventional NR techniques under
      challenging listening condition, the proposed NC + DDAE NR approach has superior
      noise suppression capabilities and gives less distortion for the key speech
      envelope information, thus, improving speech recognition more effectively for
      Mandarin CI recipients. The results suggest that the proposed deep learning-based
      NR approach can potentially be integrated into existing CI signal processors to
      overcome the degradation of speech perception caused by noise.

PMID- 29360688
TI  - Theoretical Coalescence: A Method to Develop Qualitative Theory: The Example of
      Enduring.
AB  - BACKGROUND: Qualitative research is frequently context bound, lacks
      generalizability, and is limited in scope. OBJECTIVES: The purpose of this
      article was to describe a method, theoretical coalescence, that provides a
      strategy for analyzing complex, high-level concepts and for developing
      generalizable theory. Theoretical coalescence is a method of theoretical
      expansion, inductive inquiry, of theory development, that uses data (rather than
      themes, categories, and published extracts of data) as the primary source for
      analysis. Here, using the development of the lay concept of enduring as an
      example, I explore the scientific development of the concept in multiple settings
      over many projects and link it within the Praxis Theory of Suffering. METHODS: As
      comprehension emerges when conducting theoretical coalescence, it is essential
      that raw data from various different situations be available for
      reinterpretation/reanalysis and comparison to identify the essential features of
      the concept. The concept is then reconstructed, with additional inquiry that
      builds description, and evidence is conducted and conceptualized to create a more
      expansive concept and theory. RESULTS: By utilizing apparently diverse data sets
      from different contexts that are linked by certain characteristics, the essential
      features of the concept emerge. Such inquiry is divergent and less bound by
      context yet purposeful, logical, and with significant pragmatic implications for
      practice in nursing and beyond our discipline. CONCLUSION: Theoretical
      coalescence is a means by which qualitative inquiry is broadened to make an
      impact, to accommodate new theoretical shifts and concepts, and to make
      qualitative research applied and accessible in new ways.

PMID- 29360689
TI  - Resveratrol protects early brain injury after subarachnoid hemorrhage by
      activating autophagy and inhibiting apoptosis mediated by the Akt/mTOR pathway.
AB  - Early brain injury (EBI) plays a key role in determining the prognosis of
      patients suffering from subarachnoid hemorrhage (SAH). Resveratrol, a natural
      polyphenol, serves a neuroprotection function on EBI after SAH. However, the
      potential mechanism of resveratrol on EBI remains to be elucidated. Akt, also
      known as protein kinase B, and mammalian target of rapamycin (mTOR), the
      downstream protein of Akt, play key roles in cell survival and apoptosis, cell
      cycle regulation, and cellular protein homeostasis. In the present study, we
      examined the effect of resveratrol on EBI and their potential relationship with
      the Akt/mTOR pathway, autophagy, and apoptosis. Rats received intraperitoneal
      administration of resveratrol or vehicle immediately after establishing SAH
      model. We found that mortality and brain edema were significantly lower, whereas
      the neurological score was higher for resveratrol-treated rats. HE staining
      showed that resveratrol significantly reduced the neuronal pyknosis and swelling
      in the resveratrol-treated rats compared with SAH rats. The results were assessed
      by western blot, reverse transcription-PCR , and immunohistochemistry and
      immunofluorescence at 24 h after injury to determine changes in the expression of
      the Akt/mTOR signaling pathway, autophagy, and apoptosis proteins. Western blot
      analysis showed that the expression of beclin-1, LC3-II, LC3-II/LC3-I, and Bcl-2
      was increased in resveratrol-treated rats, whereas the expression of p-Akt, p
      mTOR, p62, cleaved caspase-3, caspase-9, and Bcl-2-associated X protein was
      decreased. Immunohistochemistry analysis of beclin-1, LC3-B treated with
      resveratrol alone or in combination with 3-methyladenine (autophagy inhibitor)
      suggested that resveratrol induced the autophagy process and the inhibitor
      blocked the occurrence of autophagy, and also increased the number of terminal
      deoxynucleotidyl transferase-mediated digoxigenin-DUTP-biotin nick-end labeling
      (+) cells. Taken together, these findings indicate that resveratrol exerts
      neuroprotective effects on EBI after SAH by regulating autophagy and apoptosis
      mediated by the Akt/mTOR pathway.

PMID- 29360690
TI  - Predicting 6- and 12-Month Risk of Mortality in Patients With Platinum-Resistant
      Advanced-Stage Ovarian Cancer: Prognostic Model to Guide Palliative Care
      Referrals.
AB  - OBJECTIVE: Predictive models are increasingly being used in clinical practice.
      The aim of the study was to develop a predictive model to identify patients with
      platinum-resistant ovarian cancer with a prognosis of less than 6 to 12 months
      who may benefit from immediate referral to hospice care. METHODS: A retrospective
      chart review identified patients with platinum-resistant epithelial ovarian
      cancer who were treated at our institution between 2000 and 2011. A predictive
      model for survival was constructed based on the time from development of platinum
      resistance to death. Multivariate logistic regression modeling was used to
      identify significant survival predictors and to develop a predictive model. The
      following variables were included: time from diagnosis to platinum resistance,
      initial stage, debulking status, number of relapses, comorbidity score, albumin,
      hemoglobin, CA-125 levels, liver/lung metastasis, and the presence of a
      significant clinical event (SCE). An SCE was defined as a malignant bowel
      obstruction, pleural effusion, or ascites occurring on or before the diagnosis of
      platinum resistance. RESULTS: One hundred sixty-four patients met inclusion
      criteria. In the regression analysis, only an SCE and the presence of liver or
      lung metastasis were associated with poorer short-term survival (P < 0.001). Nine
      percent of patients with an SCE or liver or lung metastasis survived 6 months or
      greater and 0% survived 12 months or greater, compared with 85% and 67% of
      patients without an SCE or liver or lung metastasis, respectively. CONCLUSIONS:
      Patients with platinum-resistant ovarian cancer who have experienced an SCE or
      liver or lung metastasis have a high risk of death within 6 months and should be
      considered for immediate referral to hospice care.

PMID- 29360691
TI  - Age at disease onset of inflammatory bowel disease is associated with later
      extraintestinal manifestations and complications.
AB  - INTRODUCTION: A small but increasing number of patients with inflammatory bowel
      disease are diagnosed during childhood or adolescence, and disease distribution
      and severity at onset vary according to the age at diagnosis. Clinical factors
      present at the time of diagnosis can be predictive of the disease course. AIM:
      The aim of this study was to characterize disease behavior and the cumulative
      complications and extraintestinal manifestations 10 years after the diagnosis and
      to assess their association with age at diagnosis. PATIENTS AND METHODS: Data of
      patients participating with the Swiss IBD cohort study registry, a disease
      duration of 10 years and a complete data set were analyzed. The outcome was
      defined as the cumulative change of disease behavior, the occurrence of extra
      intestinal manifestations or complications, and the necessity for medical or
      surgical interventions. RESULTS: A total of 481 patients with Crohn's disease
      (CD) and 386 patients with ulcerative colitis (UC), grouped according to disease
      onset before 10, 17, 40, or after 40 years of age, were analyzed. Despite
      differences in sex, initial disease location, and smoking habits, at 10 years
      after the diagnosis, no difference was found regarding disease behavior in CD or
      regarding progression of disease extension in UC. Similarly, no age-of-onset
      dependent cumulative need for medical or surgical therapies was found. However,
      higher rates of anemia and lower rates of arthralgia and osteopenia were found in
      both pediatric-onset CD and UC, and a tendency toward higher rates of stomatitis
      in pediatric-onset CD, and of primary sclerosing cholangitis and ankylosing
      spondylitis in pediatric-onset UC. CONCLUSION: After 10 years of disease
      evolution, age at disease onset is not anymore associated with disease behavior
      but only with a small difference in the occurrence of specific extraintestinal
      manifestations and complications.

PMID- 29360692
TI  - Medically unexplained physical symptoms in patients visiting the emergency
      department: an international multicentre retrospective study.
AB  - OBJECTIVE: The objective of this study was to assess the incidence and
      characteristics of patients presenting with physical symptoms that remain
      medically unexplained at the emergency department (ED). PATIENTS AND METHODS: A
      retrospective chart study was carried out in three hospitals in The Netherlands
      and Belgium. All patients (age>18 years) visiting the ED in 4 selected weeks in
      2013 at the Erasmus University Medical Center (Erasmus MC) in Rotterdam, The
      Netherlands, and 1 selected week in 2013 at the Haaglanden Medical Center,
      Westeinde HMC in The Hague, The Netherlands, and the University Hospital Ghent
      (UZG), Belgium were included. Descriptive statistics were used for data analysis.
      RESULTS: A total of 2869 patients (Erasmus MC 1674, HMC 691, UZG 504) were
      included. Medically unexplained physical symptoms in the emergency department
      (EDMUPS) were present in 13.4% of all ED visits (Erasmus MC 12.5%, HMC 18.7%, UZG
      9.1%). No EDMUPS were identified in trauma patients. When excluding trauma
      patients, EDMUPS were present in 18.5% (Erasmus MC 16.8%, HMC 26.5%, UZG 13.3%)
      of the visits. The characteristics of patients with and without EDMUPS differed
      significantly; patients with EDMUPS were more often younger, female, self
      referred, frequent visitors, were prescribed less medication and more often had a
      psychiatric disease. Dutch and Belgian Hospital differed in the distribution of
      patients in triage categories and in the incidence of psychiatric illnesses.
      CONCLUSION: Physical symptoms remain unexplained in a significant number of
      patients at the time of ED assessment.

PMID- 29360693
TI  - The relationship between semiquantitative parameters derived from technetium-99m
      metoxyisobutylisonitrile dual-phase parathyroid single-photon emission computed
      tomography images and disease severity in primary hyperparathyroidism.
AB  - OBJECTIVE: The relationship between multiple semiquantitative indices on
      technetium-99m metoxyisobutylisonitrile (Tc-99m MIBI) parathyroid single-photon
      emission computed tomography (SPECT) and clinical, laboratory, and radiological
      data was investigated in primary hyperparathyroidism. PATIENTS AND METHODS:
      Ninety-three patients who had a histopathologically confirmed single parathyroid
      adenoma (PT) were enrolled. Regions of interests were drawn around the PT,
      neighboring thyroid (T), and background in early and late planar images and
      isocontour regions of interests around the adenoma in SPECT images (PT SPECT).
      The relationships between early and late PT, parathyroid adenoma
      counts/neighboring thyroid counts, parathyroid counts-thyroid counts (PT-T), PT
      washout, retention index, PT SPECT and serum parathormone (PTH), Ca, P, urinary
      Ca levels, weight of the adenoma, neck ultrasonography, renal ultrasonography,
      and bone mineral density findings were investigated. RESULTS: There was a
      positive correlation between the weight of the adenoma and serum PTH and calcium
      (Ca) levels (P<0.001), between serum PTH and Ca levels (P<0.001), early PT-T and
      serum Ca levels (P=0.027), late PT-T and weight of the adenoma (P=0.04), and PT
      SPECT and serum Ca levels (P=0.046) and a reverse correlation between PT SPECT
      and serum phosphorus (P) levels (P=0.04). Serum Ca levels were significantly
      higher and P levels were lower in the group with PT SPECT values above 116. PT
      SPECT and late parathyroid adenoma counts/neighboring thyroid counts values were
      significantly higher in the group with serum Ca levels of more than 11 mg/dl.
      Femoral T and Z scores were significantly lower in patients with lower PT
      washout. Early PT was significantly lower in patients with coexisting thyroiditis
      compared with patients with both thyroiditis and thyroid nodules (P=0.034).
      CONCLUSION: Semiquantitative evaluation of a Tc-99m MIBI parathyroid SPECT study
      may help predict disease severity in primary hyperparathyroidism.

PMID- 29360694
TI  - Attenuation correction in myocardial perfusion imaging affects the assessment of
      infarct size in women with previous inferior infarct.
AB  - BACKGROUND: Myocardial perfusion imaging is a well-established diagnostic tool in
      patients with known or suspected coronary artery disease. Numerous clinical
      trials have shown that attenuation correction (AC) in single photon emission
      computed tomography (SPECT) improves the diagnostic accuracy of myocardial
      perfusion imaging over non-AC SPECT, differentiating between scar and attenuation
      artifacts. We have previously shown that attenuation artifacts produce an
      overestimation of the size of inferior infarcts in the male population. It is
      assumed that women are less affected by inferior attenuation artifacts than men.
      PURPOSE: The aim of this study is to evaluate the role of AC in the assessment of
      infarct size in female patients with a history of myocardial inferior infarct.
      PATIENTS AND METHODS: We studied a population of 66 consecutive women, with a
      history of previous inferior myocardial infarct, by SPECT/computed tomography
      (CT) with 370+370 MBq of technetium-99m labeled compounds by a 2-day stress-rest
      protocol. Both AC and uncorrected gated-SPECT/CT studies were reconstructed after
      scatter and motion correction by ordered-subset expectation maximization
      iterative reconstruction and resolution recovery. The coregistration of the
      transmission and emission scans was verified for all patients; any misalignment
      was realigned manually. Uncorrected and corrected SPECT images were analyzed by
      software QPS/QGS package using a 17-segment model. For each segment, perfusion
      and wall motion were quantified using a five-point score according to the
      American Society of Nuclear Cardiology guidelines. Summed stress, summed rest
      score (SRS), and summed difference score of the inferior left ventricle wall
      (inferior, inferoseptal, inferolateral, and apical inferior segments) were
      calculated. A linear correlation was used to assess the relationship between
      perfusion and the regional wall motion score as determined by uncorrected gated
      SPECT. RESULTS: The results of quantitative analysis of non-AC and CT-AC SPECT
      images, respectively, were as follows: summed stress score: 9.47+/-5.01 and
      6.58+/-4.77% (P<0.001); SRS was 6.05+/-5.02 and 4.14+/-4.12% (P<0.001); the
      summed difference score was 2.92+/-2.74 and 2.52+/-2.63% (P=NS), respectively.
      The correlation between corrected and uncorrected SRS and the regional summed
      wall motion score of the same segment was R=0.31 versus R=0.34. CONCLUSION: In
      the female population, like in men, attenuation artifacts affect the calculation
      of the infarct size of the inferior wall, with overestimation of the infarct size
      in uncorrected images. The AC regional perfusion score (SRS) better correlates
      with the regional wall motion score of the inferior wall in women with previous
      inferior infarct.

PMID- 29360695
TI  - The Importance of Publications by Public Health Practitioners: A New Tool.

PMID- 29360696
TI  - Developing an Informatics-Savvy Health Department: From Discrete Projects to a
      Coordinating Program-Part III, Ensuring Well-Designed and Effectively Used
      Information Systems.

PMID- 29360697
TI  - The Public Health Community Platform, Electronic Case Reporting, and the Digital
      Bridge.
AB  - At the intersection of new technology advancements, ever-changing health policy,
      and fiscal constraints, public health agencies seek to leverage modern technical
      innovations and benefit from a more comprehensive and cooperative approach to
      transforming public health, health care, and other data into action. State health
      agencies recognized a way to advance population health was to integrate public
      health with clinical health data through electronic infectious disease case
      reporting. The Public Health Community Platform (PHCP) concept of bidirectional
      data flow and knowledge management became the foundation to build a cloud-based
      system connecting electronic health records to public health data for a select
      initial set of notifiable conditions. With challenges faced and lessons learned,
      significant progress was made and the PHCP grew into the Digital Bridge, a
      national governance model for systems change, bringing together software vendors,
      public health, and health care. As the model and technology advance together,
      opportunities to advance future connectivity solutions for both health care and
      public health will emerge.

PMID- 29360699
TI  - Barriers for Hospital-Based Nurse Practitioners Utilizing Clinical Decision
      Support Systems: A Systematic Review.
AB  - There is a national focus on the adoption of healthcare technology to improve the
      delivery of safe, efficient, and high-quality patient care. Nurse practitioners
      fulfill an emerging strategic role in the hospital setting. A comprehensive
      literature review focused on the question: What are the barriers for nurse
      practitioners utilizing clinical decision support in the hospital setting? Nine
      studies conducted from 2011 to 2017 were the basis for this review, which
      identified 13 barriers for nurse practitioners utilizing clinical decision
      support in the hospital. Having the right information, including up-to-date
      evidence-based practice guidelines, accurate clinical pathways, and current
      clinical algorithms, was the most common barrier. Providing reliable clinical
      decision support is crucial as nurse practitioners become more dependent on
      hospital technology systems in the delivery of safe patient care. Eliminating
      barriers to the use of clinical decision support is important for informaticists
      and nurse practitioners because both groups concentrate on acceptance of decision
      support systems in the hospital to meet the goal of safe and high-quality patient
      care.

PMID- 29360700
TI  - Professionals' Use of a Multidisciplinary Communication Tool for Patients With
      Dementia in Primary Care.
AB  - In this descriptive study, the use of a professional e-communication tool,
      Congredi, is evaluated. Ninety-six Congredi records of patients with dementia
      could be divided into the subgroups low-complex care (n = 43) and high-complex
      care (n = 53). If Congredi is an adequate communication tool for professionals,
      the changing involvement of caregivers must also be reflected within the two
      subgroups. We hypothesized that use would be more intensive in the high-complex
      group in comparison with the low-complex group. Data were gathered during 42
      weeks. Results showed that the mean number of care activities in the high-complex
      group was significantly higher than in the low-complex group (10.43 vs 5.61, P =
      .001). The number of professionals involved with the high-complex care group
      (3.58) was higher compared to the low-complex care group (2.51) (P = .000). The
      most frequent use was by case managers and nurses (43.4%) in the high-complex
      group and by several case managers (41.9%) in the low-complex group. It was
      concluded that professionals used Congredi adequately in the multidisciplinary
      care of patients with dementia because the changing involvement of caregivers and
      the level of care activities were reflected in the use of Congredi.

PMID- 29360701
TI  - Intracorporeal Anastomosis Reduces Surgical Stress Response in Laparoscopic Right
      Hemicolectomy: A Prospective Randomized Trial.
AB  - Total laparoscopic right hemicolectomy is a procedure that involves an
      intracorporeal anastomosis. This approach may reduce tissue injury resulting in a
      significant lower surgical stress response (SSR) compared with the same procedure
      performed with an extracorporeal anastomosis. The purpose of this study was to
      compare the SSR level between 2 groups of patients undergoing laparoscopic right
      hemicolectomy with intracorporeal or extracorporeal anastomosis. From June 2015
      to December 2016, 60 patients were enrolled and randomized. Interleukin-6, C
      reactive protein, procalcitonin, white blood cell count, cortisol, prolactin,
      prealbumin, albumin, triglycerides, and transferrin were analyzed preoperatively
      and at 1, 3, and 5 days postoperatively. Interleukin-6 and C-reactive protein
      levels were significantly lower in the intracorporeal group on days 1, 3, and 5
      postoperatively compared with the extracorporeal group. Gastrointestinal recovery
      was significantly earlier in the intracorporeal group. The intracorporeal
      anastomosis in laparoscopic right hemicolectomy reduces SSR, which may play a
      role in bowel recovery.

PMID- 29360702
TI  - Initial Experience of Single-port Laparoscopic Multivisceral Resection for
      Locally Advanced Colon Cancer.
AB  - AIM: The aim of this study was to evaluate the safety and feasibility of single
      port laparoscopic multivisceral resection (SLMVR) for locally advanced colon
      cancer invading or adhering to neighboring organs. METHOD: A prospectively
      collected database was collated of all patients undergoing SLMVR from January
      2011 to December 2014. Short-term and long-term oncologic outcomes were
      evaluated. RESULTS: Thirty consecutive patients who underwent SLMVR were
      identified and the completion rate was 90%. The R0 resection rate of the primary
      tumor was 100%. The postoperative complication rate was 23.3%. The 3-year relapse
      free survival rates of patients with stage II (n=11) and stage III (n=12) disease
      were 80.8% and 54.6%, respectively. The 5-year overall survival rates of patients
      with stage II and stage III disease were 75.8% and 75.0% over a median follow-up
      of 42 months, respectively. CONCLUSIONS: SLMVR for locally advanced colon cancer
      is safe and feasible in selected patients.

PMID- 29360703
TI  - Association between polycystic ovary syndrome and hot flash presentation during
      the midlife period.
AB  - OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in
      reproductive-aged women; however, the impact of PCOS on menopausal symptoms
      remains poorly understood. This study aims to determine the influence of PCOS on
      hot flash presentation in midlife women. METHODS: Participants were recruited
      from the Midlife Women's Health Study involving 780 women aged 45 to 54 years.
      All women completed detailed questionnaires on hot flash symptoms. Between June
      2014 and March 2015, participants were screened for history of PCOS based on the
      Rotterdam criteria. Fisher's exact tests and Wilcoxon rank-sum tests were used
      for analysis. Multivariate logistic regression was performed to identify factors
      associated with hot flashes at midlife. RESULTS: In all, 453 women (69%)
      consented to the telephone interview and 9.3% (n = 42) met diagnostic criteria
      for PCOS; 411 were included as controls. Mean age was 48.0 and body mass index
      was 27.3 for women with PCOS. The majority of participants were white (72%).
      There was no difference between PCOS and control women for levels of follicle
      stimulating hormone, testosterone, progesterone, or estradiol. Multivariate
      logistic regression demonstrated that PCOS was not associated with increased odds
      of hot flash incidence. Smoking was the only variable associated with
      experiencing hot flashes (odds ratio 2.0, 95% confidence interval 1.05-3.98).
      CONCLUSIONS: A history of PCOS was not associated with increased hot flash
      symptoms during the midlife period. Additional research should continue to
      investigate the health and quality of life associated with a history of PCOS in
      the aging population.

PMID- 29360704
TI  - Association between insulin resistance and the magnetic resonance spectroscopy
      determined marrow fat fraction in nondiabetic postmenopausal women.
AB  - OBJECTIVE: The clinical consequences of insulin resistance and hyperinsulinemia
      on marrow lipid remain elusive. We aimed to explore the effects of anthropometric
      and biochemical measures, that is, estimates of insulin resistance, on marrow
      lipid accumulation in nondiabetic postmenopausal women using magnetic resonance
      (MR) spectroscopy. METHODS: The study participants were 91 nondiabetic
      postmenopausal women. Marrow fat fraction (FF) at the L3 vertebral body by single
      voxel MR spectroscopy and bone mineral density (BMD) by dual-energy x-ray
      absorptiometry were measured. Their glucose and lipid metabolism were determined
      by biochemical analysis, and their insulin sensitivity was evaluated using the
      Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: Adjusted
      for multiple covariates including age, years since menopause, body mass index,
      alcohol intake, tobacco use, physical activity, and serum lipid profile, the mean
      FF was significantly increased, and BMD at the lumbar spine, femoral neck, and
      total hip decreased as quartiles of HOMA-IR increased (P for trends <0.01). HOMA
      IR had a positive association with FF (mean difference 0.300, P < 0.001) and a
      negative association with BMD at the lumbar spine (mean difference -0.182, P =
      0.016), total hip (mean difference -0.219, P = 0.001), and femoral neck (mean
      difference -0.195, P = 0.013). The above described associations of HOMA-IR with
      FF, lumbar spine, and total hip BMD remained essentially unchanged; however, the
      association with femoral neck BMD lost significance after adjusting for the
      aforementioned confounders. CONCLUSION: In nondiabetic postmenopausal women,
      insulin resistance is correlated with marrow lipid expansion. This association
      persists after adjusting for the body mass index and other potential covariates,
      suggesting an independent effect of insulin resistance on marrow adiposity.

PMID- 29360705
TI  - Determination of Examination-Specific Diagnostic Reference Level in Computed
      Tomography by A New Quality Control-Based Dose Survey Method.
AB  - A new "quality-control-based (QC-based) dose survey method" has been developed
      for determination of diagnostic reference levels (DRL) in Computed Tomography
      (CT) examinations. The "QC-based dose survey method" is based on the use of
      retrospective data in the QC documents and reports, which are typically available
      from the National Regulatory Authority database. The method was applied to 70 CT
      scanners in Tehran, Iran, by using the available QC reports from the database.
      The commonly used "data collection method" was also applied by filling each
      questionnaire on-site to validate the new method. Using the new QC-based and data
      collection methods, the DRLs of four common CT examinations: head, sinus, chest,
      and abdomen/pelvis were determined and compared. The DRLs determined by the "QC
      based method" for head, sinus, chest, and abdomen/pelvis are 59, 29, 10, and 13
      mGy, respectively, for the volume computed tomography dose index (CTDIVol) and
      834, 235, 233, and 522 mGy-cm for the dose length product (DLP), respectively.
      The difference between the DRLs obtained by the two methods is on the average 6.7
      +/- 5.7%, which is within the acceptance tolerance level of the IAEA for QC
      dosimetry tests. The "QC-based dose survey method" is believed to be an effective
      alternative method to the other commonly used "data collection" and "direct dose
      measurement method" for determination of CT examination DRLs. This new method has
      unique characteristics such as simplicity, time and cost effectiveness, highly
      reduced clinical interruptions and collaborations, and potential for large-scale
      surveys with capability for more frequent review of national DRL values.

PMID- 29360706
TI  - Measurement and Simulation of the Counting Efficiency of a Whole-body Counter
      Using a BOMAB Phantom Inserted with Rod Sources Containing Mixed Radionuclides.
AB  - The examination of internal contamination is important for providing an adequate
      medical response during a radiological emergency. A whole-body counting system
      can assess gamma-emitting radionuclides in a human body when monitoring internal
      contamination. It is necessary to calibrate whole-body counting systems by using
      a calibration phantom, such as a Bottle Manikin Absorption phantom, to properly
      assess internal contamination. However, the total weight of the Bottle Manikin
      Absorber phantom is high, and there can be leakage of radioactive sources, which
      are disadvantages of using such a phantom. This study proposes a calibration
      phantom that is designed to overcome these disadvantages. The proposed phantom
      consists of rod sources that are inserted in each part of the phantom. The
      counting efficiency of the rod-source-inserted calibration phantom was acquired
      using a Monte Carlo simulation method, but the results were evaluated by
      comparing the experimental efficiencies with those of a conventional Bottle
      Manikin Absorption phantom by using two commercial whole-body counting systems
      (stand-up type and bed type). The efficiency curve of the rod-source-inserted
      phantom matched well that of the conventional calibration phantom. The relative
      deviation between the efficiencies of the conventional Bottle Manikin Absorption
      phantom and the proposed calibration phantom in both whole-body counting systems
      was less than 11%, and the total weight of the phantom was also reduced. These
      results suggest that the proposed phantom can be manipulated more easily and
      replace the conventional Bottle Manikin Absorption calibration phantom for these
      two types of whole-body counting systems.

PMID- 29360707
TI  - Application of the ICRP 67 and NCRP 156 Biokinetic Models to 241 Am Wound Data
      from Nonhuman Primates.
AB  - Distribution, retention, and excretion of intramuscularly injected Am citrate
      have been investigated in cynomolgus and rhesus nonhuman primates (NHP). Bioassay
      and retention data, obtained from experiments done by Patricia Durbin and her
      colleagues at Lawrence Berkeley National Laboratory, were evaluated against the
      International Commission on Radiological Protection (ICRP 67) Am systemic model
      coupled with to the National Council on Radiation Protection and Measurement
      wound model (NCRP 156). The default transfer rates suggested in these models were
      used with the urine and feces excretion data to predict the intake as well as
      liver and skeleton tissue contents at the time of death. The default models
      adequately predict the animals' urine bioassay data, but the injected activities
      were overpredicted by as much 4.41 times and underpredicted by as much as 0.99
      times. Poor prediction has been observed in all cases using fecal excretion. The
      retained activity in the liver and skeleton were investigated using the same
      approach. It appears that the models predict the amount of the activity retention
      in the skeleton more accurately than in the liver. The fraction of predicted to
      measured activity at the time of death in the skeleton was over 1.0 in most
      cases, and accurate predictions were obtained in seven cases. The predicted
      activity in skeleton for these cases ranged from 2.7 to 17% overestimated
      activity and from 9 to 14% underestimated activity. NHPs' urine data and organ
      retention were compared with data from previously modeled baboons and beagle
      dogs. About 6% of the injected activity in baboons and beagle dog was excreted in
      urine and approximately 0.1% in feces in the first 24 h. The results from NHP are
      not different from excreta analysis in these other species. Urinary excretion in
      the cynomolgus, rhesus, and baboon NHP is the dominant pathway of Am clearance;
      however, fecal excretion is considered dominant in beagle dogs. The comparison
      between NHPs and humans is difficult due to the differences in the number of
      activities translocated or deposited in the liver tissue and nonliver tissues
      (primarily skeleton), in addition to the physiological differences between the
      NHPs and humans.

PMID- 29360709
TI  - Some Considerations for Chelation Treatment and Surgical Excision Following
      Incorporation of Plutonium in Wounds.
AB  - After a plutonium-contaminated wound, the role of an internal dosimetrist is to
      inform the patient and the physician of the dosimetric considerations. The doses
      averted due to medical treatments (excision or chelation) are higher if the
      treatments are administered early; therefore, the internal dosimetrist needs to
      rely on limited information on wound counts and process knowledge for advising
      the physician. Several wound cases in the literature were reviewed to obtain
      estimates of the efficacies of surgical excision and chelation treatment after
      plutonium-contaminated wounds. The dose coefficients calculated by coupling the
      NCRP 156 wound model with the systemic model were used to derive the decision
      guidelines that may indicate medical treatment based on 1) the concept of saved
      doses proposed by the NCRP 156 wound model, 2) the limits recommended by the
      CEC/DOE guidebook, and 3) the Clinical Decision Guidelines proposed in NCRP
      Report No. 161. These guidelines by themselves, however, are of limited use for
      several reasons, including 1) large uncertainties associated with wound
      measurements, 2) exposure to forms of radionuclides that cannot be assigned to a
      single category in the NCRP 156 framework, 3) inability of the NCRP 156 model to
      explain some of the wound cases in the literature, 4) neglect of the local doses
      to the wound site and the pathophysiological response of the tissue, 5) poorly
      understood relationship between effective doses and risks of late health effects,
      and 6) disregard of the psychological aspects of radionuclide intake.

PMID- 29360708
TI  - Screening Internal Contamination of Inhaled and Ingested Radionuclides with Hand
      held Survey Meters.
AB  - During the aftermath of a radiological accident or attack, the rapid
      identification of individuals who have internalized medically significant amounts
      of material is paramount to guide medical and public health decisions. This paper
      explores the utility of hand-held, pancake GM detectors to determine if an
      individual has inhaled Sr, Cs, Pu, Pu, or Am in quantities requiring treatment.
      Additionally, ingestion of Sr or Cs was considered. Both Sr and Cs were modeled
      in equilibrium with their progeny, but the progeny of Pu, Pu, and Am were
      excluded. Treatment thresholds are defined using the National Council on
      Radiation Protection & Measurements' (NCRP) clinical decision guides (CDGs).
      Using Monte Carlo N-Particle (MCNP) modeling software, a human phantom and
      detector were modeled to determine the activity required to achieve a detector
      reading of twice background 1, 7, or 30 d post-ingestion or post-inhalation.
      Modeling found that inhaled Pu, Pu, and Am are detectable only if the
      contaminated individual inhaled thousands-fold more material than the CDG. This
      lack of detectability means that hand-held GM detectors are inappropriate for
      initial screening for americium or plutonium and that more intensive screening is
      necessary to confirm suspected contamination. Cesium-137, by contrast, could be
      detected at levels 10- to 100-fold lower than the amount requiring treatment,
      allowing quick differentiation between contaminated and uncontaminated
      individuals. Surprisingly, Sr was detectable within a factor of 2 of the amount
      requiring treatment. Detection of Sr was due primarily to bremsstrahlung
      radiation from beta interactions with calcium in bone. While rapid screening
      could identify individuals contaminated by Cs and possibly with Sr, further
      screening of identified individuals is necessary to establish medical need.
      However, these contaminated individuals could still be prioritized for further
      testing and possible presumptive treatment. Based on the findings of this study,
      concepts of operation for the use of hand-held survey meters should be developed
      for the screening of individuals potentially internally contaminated with Cs and
      Sr.

PMID- 29360710
TI  - Deterministic Effects to the Lens of the Eye Following Ionizing Radiation
      Exposure: is There Evidence to Support a Reduction in Threshold Dose?
AB  - Ionizing radiation exposure to the lens of the eye is a known cause of
      cataractogenesis. Historically, it was believed that the acute threshold dose for
      cataract formation was 5 Sv, and annual dose limits to the lens were set at 150
      mSv. Recently, however, the International Commission on Radiological Protection
      has reduced their threshold dose estimate for deterministic effects to 0.5 Gy and
      is now recommending an occupational limit of 20 mSv per year on average. A number
      of organizations have questioned whether this new threshold and dose limit are
      justified based on the limited reliable data concerning radiation-induced
      cataracts. This review summarizes all of the published human epidemiological data
      on ionizing radiation exposure to the lens of the eye in order to evaluate the
      proposed threshold. Data from a variety of exposure cohorts are reviewed,
      including atomic bomb survivors, Chernobyl liquidators, medical workers, and
      radiotherapy patients. Overall, there is not conclusive evidence that the
      threshold dose for cataract formation should be reduced to 0.5 Gy. Many of the
      studies reviewed here are challenging to incorporate into an overall risk model
      due to inconsistencies with dosimetry, sample size, and scoring metrics.
      Additionally, risk levels in the studied cohorts may not relate to occupational
      scenarios due to differences in dose rate, radiation quality, age at exposure and
      latency period. New studies should be designed specifically focused on
      occupational exposures, with reliable dosimetry and grading methods for lens
      opacities, to determine an appropriate level for dose threshold and exposure
      limit.

PMID- 29360711
TI  - Comments on "Space: The Final Frontier-Research Relevant to Mars".

PMID- 29360713
TI  - ERRATUM: Practical Considerations for Gamma Ray Spectroscopy with NaI(Tl): A
      Tutorial.

PMID- 29360712
TI  - Reply to Doss et al.

PMID- 29360717
TI  - Noncompliance with American College of Surgeons Committee on Trauma recommended
      criteria for full trauma team activation is associated with undertriage deaths.
AB  - BACKGROUND: The appropriate triage of acutely injured patients within a trauma
      system is associated with improved rates of mortality and optimal resource
      utilization. The American College of Surgeons Committee on Trauma (ACS-COT) put
      forward six minimum criteria (ACS-6) for full trauma team activation (TTA). We
      hypothesized that ACS-COT-verified trauma center compliance with these criteria
      is associated with low undertriage rates and improved overall mortality. METHODS:
      Data from a state-wide collaborative quality initiative was used. We used data
      collected from 2014 through 2016 at 29 ACS verified Level I and II trauma
      centers. Inclusion criteria are: adult patients (>=16 years) and Injury Severity
      Score of 5 or less. Quantitative data existed to analyze four of the ACS-6
      criteria (emergency department systolic blood pressure <= 90 mm Hg, respiratory
      compromise/intubation, central gunshot wound, and Glasgow Coma Scale score < 9).
      Patients were considered to be undertriaged if they had major trauma (Injury
      Severity Score > 15) and did not receive a full TTA. RESULTS: 51,792 patients
      were included in the study. Compliance with ACS-6 minimum criteria for full TTA
      varied from 51% to 82%. The presence of any ACS-6 criteria was associated with a
      high intervention rate and significant risk of mortality (odds ratio, 16.7; 95%
      confidence interval, 15.2-18.3; p < 0.001). Of the 1,004 deaths that were not a
      full activation, 433 (43%) were classified as undertriaged, and 301 (30%) had at
      least one ACS-6 criterion present. Undertriaged patients with any ACS-6 criteria
      were more likely to die than those who were not undertriaged (30% vs. 21%, p =
      0.001). Glasgow Coma Scale score less than 9 and need for emergent intubation
      were the ACS-6 criteria most frequently associated with undertriage mortality.
      CONCLUSION: Compliance with ACS-COT minimum criteria for full TTA remains
      suboptimal and undertriage is associated with increased mortality. These data
      suggest that the most efficient quality improvement measure around triage should
      be ensuring compliance with the ACS-6 criteria. This study suggests that practice
      pattern modification to more strictly adhere to the minimum ACS-COT criteria for
      full TTA will save lives. LEVEL OF EVIDENCE: Care management, level III.

PMID- 29360718
TI  - Featured Articles for CME Credit February 2018.

PMID- 29360714
TI  - Temporal Fluctuations in Indoor Background Gamma Radiation Using NaI(Tl).
AB  - An enhanced understanding of background gamma radiation is necessary for accurate
      radionuclide activity quantification. Background spectra are routinely subtracted
      from spectra of samples prepared in known geometries, with data collection time
      chosen to optimize statistics for counting uncertainties. The work presents
      measured background spectra collected inside and outside shields of varying
      geometry and composition, showing the effects of these on background. Gamma
      background measurements with and without blank samples are included along with
      spectra from different sizes and shapes of NaI(Tl) detectors. If the environment
      is being monitored for quick and confident detection of recently appearing
      radiation sources, a thorough knowledge of the background radiation and its
      temporal variation is essential. To study the requirements of such background
      measurements, sequential background gamma radiation collections were obtained on
      an hourly basis for a total of 316 h from an unshielded 5.5 * 11 * 40 cm NaI(Tl)
      detector located inside a laboratory setting where small sources are routinely
      stored and used. Finally, a strategy for optimizing data collection times and
      analyzing background gamma radiation spectra for long-term radionuclide
      monitoring is presented.

PMID- 29360720
TI  - Introduction by the Guest Editors: The PD-1 Axis in Cancer Therapy: The Irony in
      a Name.

PMID- 29360721
TI  - Preclinical Data Supporting Antitumor Activity of PD-1 Blockade.
AB  - Antibodies that block the PD-1 coinhibitory receptor on T cells or its primary
      ligand, PD-L1, have demonstrated unprecedented efficacy across a diverse array of
      both solid and hematologic malignancies in the clinic. These advances were built
      on a foundation of murine preclinical tumor model studies, which both
      demonstrated the therapeutic potential of PD-1/PD-L1 antibody blockade and also
      provided critical insights into the cellular and molecular processes underlying
      their capacity to elicit immune-mediated tumor regressions. As the field of
      immunotherapy moves toward higher-order combinations of agents, effective
      utilization of murine tumor models to optimize the composition of PD-1 antibody
      combination therapies, as well as their dosing and scheduling, will be essential
      for effective clinical translation. Novel murine models bearing human tumor
      xenografts and engrafted human immune systems may help close the gap between
      preclinical and clinical immunobiology.

PMID- 29360722
TI  - Clinical Development of PD-1 in Advanced Melanoma.
AB  - The development of new treatment options has dramatically improved the landscape
      for patients with advanced melanoma. Part of these advances emerged through the
      identification of the importance of factors that regulate the immune system,
      including proteins that negatively modulate T cell-mediated responses termed
      "immune checkpoints." Indeed, blockade of the cytotoxic T lymphocyte-associated
      antigen 4 (CTLA-4) immune checkpoint served as a proof of principle that the
      manipulation of these molecules could induce robust anticancer effects, yet
      limited to a small percentage of patients. Targeting a distinct checkpoint, the
      PD-1 yielded improved outcomes and reduced toxicity compared with CTLA-4 blockade
      and, in separate studies, chemotherapy. More recently, combined CTLA-4/PD-1
      blockade was shown to result in higher response rates, while accompanied by
      increased toxicity. In this article, we review the clinical development of anti
      PD-1 monotherapy and combinations that may expand the benefit of immunotherapy
      for patients with advanced melanoma.

PMID- 29360724
TI  - Blocking PD-1/PD-L1 in Genitourinary Malignancies: To Immunity and Beyond.
AB  - Genitourinary malignancies represent a diverse biologic and immunologic
      landscape. Recently, checkpoint blockade has transformed the treatment paradigms
      for bladder and kidney cancer. However, continued progress will be essential in
      bladder and kidney cancer, given response to inhibition of the PD-1/PD-L1 (PD
      1/PD-L1) axis remains variable and only a minority of patients respond. In
      contrast with the clinical trial results in bladder and kidney cancer, studies of
      anti-PD-1/PD-L1 therapy in prostate cancer have generally been disappointing.
      Nevertheless, an exciting array of studies is underway that are translating
      lessons learned from tumor biology into promising clinical trials. Here we
      highlight important features of the immune tumor microenvironment of bladder,
      kidney, and prostate cancer and review key completed and ongoing clinical trials
      of anti-PD-1/PD-L1 therapy in these tumor types.

PMID- 29360723
TI  - PD-1/PD-L1 Axis in Lung Cancer.
AB  - Cancer immunotherapies have revolutionized the treatment of non-small cell lung
      cancer. Yet, only a small subset of patients will benefit from PD-1 or PD-L1
      blockade. PD-L1 tumor cell expression is the only approved biomarker at present.
      Tumor mutational burden and other emerging biomarkers should improve patient
      selection. Combination therapy approaches with chemotherapy or cytotoxic T
      lymphocyte-associated protein 4 blockade may increase the proportion of patients
      who benefit from immunotherapy. Although use of immunotherapy in lung cancers
      with targetable oncogenes has not been particularly successful, the benefit of PD
      (L)1 inhibitors in early-stage disease is emerging. This review briefly describes
      the evolution of the clinical development and future directions of PD-(L)1
      blockade in patients with lung cancers.

PMID- 29360725
TI  - Clinical Development of PD-1 Blockade in Hematologic Malignancies.
AB  - Clinical development of immune checkpoint inhibitors targeting the PD-1 pathway
      has led to clinical benefits for patients with multiple solid tumor and
      hematologic malignancies and has revolutionized modern oncology. High response
      rates to PD-1 blockade in patients with classical Hodgkin lymphoma and certain
      subtypes of non-Hodgkin lymphoma highlight an intrinsic biologic sensitivity to
      this strategy of treatment. Despite early success of checkpoint inhibitor and
      immunomodulatory drug combinations in phase 2 studies in multiple myeloma, safety
      concerns in patients treated with the combination of immunomodulatory drugs and
      checkpoint inhibitors in myeloma have stalled drug development in this space.
      Novel combination approaches exploring PD-1 inhibitors with epigenetic modifiers
      in leukemia are underway.

PMID- 29360726
TI  - Toxicities Associated With PD-1/PD-L1 Blockade.
AB  - Immune checkpoint inhibitors, particularly those targeting PD-1/PD-L1, produce
      durable responses in a subset of patients across cancer types. Although often
      well tolerated, these agents can induce a broad spectrum of autoimmune-like
      complications that may affect any organ system. Treatment of these toxicities
      primarily consists of immune suppression with corticosteroids and other agents.
      This review briefly discusses the mechanisms of immune-related adverse events,
      overviews the clinical and pathologic features of major toxicities caused by PD
      1/PD-L1 blockade, and reviews their management.

PMID- 29360727
TI  - PD-L1 and Emerging Biomarkers in Immune Checkpoint Blockade Therapy.
AB  - PD-L1 checkpoint blockade is revolutionizing cancer therapy, and biomarkers
      capable of predicting which patients are most likely to respond are highly
      desired. The detection of PD-L1 protein expression by immunohistochemistry can
      enrich for response to anti-PD-(L)1 blockade in a variety of tumor types, but is
      not absolute. Limitations of current commercial PD-L1 immunohistochemical (IHC)
      assays and improvements anticipated in next-generation PD-L1 testing are
      reviewed. Assessment of tumor-infiltrating lymphocytes in conjunction with PD-L1
      testing could improve specificity by distinguishing adaptive (interferon gamma
      driven and cytotoxic T-lymphocyte associated) from constitutive (non-immune
      mediated) expression. The presence of a high tumor mutational burden also
      enriches for response to therapy, and early data indicate that this may provide
      additive predictive value beyond PD-L1 IHC alone. As candidate biomarkers
      continue to emerge, the pathologist's assessment of the tumor microenvironment on
      hematoxylin-eosin stain combined with PD-L1 IHC remains a rapid and robust way to
      evaluate the tumor-immune dynamic.

PMID- 29360729
TI  - Combination Strategies PD-1/PD-L1 Antagonists.
AB  - Despite the broad clinical antitumor activity of PD-1/PD-L1 antagonists, many
      patients who are treated with these agents either do not respond or achieve
      suboptimal responses. Improving overall outcome will require combinations with
      other agents to address potential innate or acquired mechanisms of resistance.
      Many combination trials have been initiated in patients with or without prior
      exposure to the PD-1/PD-L1 antagonists. In addition to the challenge of
      identifying optimal dose, schedule, and sequence for the combinations, current
      biomarker efforts lack the precision to identify optimal combination partners for
      the PD-1/PD-L1 antagonists in individual patients. For each possible combination,
      careful consideration of clinical trial design, biomarker strategies, and
      endpoints for early clinical development will be necessary to move the most
      promising regimens forward and therefore to accelerate the rate of clinical
      progress.

PMID- 29360728
TI  - Mechanisms of Resistance to PD-1 and PD-L1 Blockade.
AB  - Cancer immunotherapy utilizing blockade of the PD-1/PD-L1 checkpoint has
      revolutionized the treatment of a wide variety of malignancies, leading to
      durable therapeutic responses not typically seen with traditional cytotoxic
      anticancer agents. However, these therapies are ineffective in a significant
      percentage of patients, and some initial responders eventually develop resistance
      to these therapies with relapsed disease. The mechanisms leading to both primary
      and acquired resistance to PD-1/PD-L1 inhibition are varied and can be both
      multifactorial and overlapping in an individual patient. As the mechanisms of
      resistance to PD-1/PD-L1 blockade continue to be further characterized, new
      strategies are being developed to prevent or reverse resistance to therapy,
      leading to improved patient outcomes.

PMID- 29360730
TI  - Physical Activity, a Critical Exposure Factor of Environmental Pollution in
      Children and Adolescents Health Risk Assessment.
AB  - It is an extremely urgent problem that physical fitness promotion must face not
      only the increasing air pollution but also the decline of physical activity level
      of children and adolescents worldwide at present, which is the major reason that
      forms an inactive lifestyle and does harm to adolescents' health. Thus, it is
      necessary to focus on the exposure factor in environmental health risk assessment
      (EHRA) which conducts supervision of environmental pollution and survey of
      adolescents' activity patterns according to the harmful characteristics of air
      pollutant and relationship between dose and response. Some countries, such as
      USA, Canada and Australia, regard both respiratory rate and physical activity
      pattern as main exposure factors for adolescents in both air pollution health
      risk assessment and exercise risk assessment to forecast a safe exposing
      condition of pollutant for adolescents while they are doing exercise outdoors. In
      addition, it suggests that the testing indexes and testing methods of these two
      exposure factors, such as investigating the time of daily physical activity,
      strength, and characteristic of frequency, help to set up the quantitative
      relationship between environmental pollution index and the time, strength,
      frequency of daily activities, and formulate children's and adolescents' activity
      instructions under different levels of environmental pollutions. As smog becomes
      increasingly serious at present, it is meaningful to take physical activity as a
      critical composition of exposure factor and establish physical activity
      guideline, so as to reduce the risk of air pollution, and promote physical health
      of children and adolescents effectively.

PMID- 29360731
TI  - Thyme and Savory Essential Oil Efficacy and Induction of Resistance against
      Botrytis cinerea through Priming of Defense Responses in Apple.
AB  - The efficacy of thyme and savory essential oils were investigated against
      Botrytis cinerea on apple fruit. Apples treated with thyme and savory essential
      oils showed significantly lower gray mold severity and incidence. Thyme essential
      oil at 1% concentration showed the highest efficacy, with lower disease incidence
      and smaller lesion diameter. The expression of specific pathogenesis-related (PR)
      genes PR-8 and PR-5 was characterized in apple tissues in response to thyme oil
      application and B. cinerea inoculation. After 6 h of pathogen inoculation, thyme
      essential oil induced a 2.5-fold increase of PR-8 gene expression compared to
      inoculated fruits. After 24 h of inoculation, PR-8 was highly induced (7-fold) in
      both thyme oil-treated and untreated apples inoculated with B. cinerea. After 48
      h of inoculation, PR-8 expression in thyme-treated and inoculated apples was 4-
      and 6-fold higher than in inoculated and water-treated apples. Neither thyme oil
      application nor B. cinerea inoculation markedly affected PR-5 expression. These
      results suggest that thyme oil induces resistance against B. cinerea through the
      priming of defense responses in apple fruit, and the PR-8 gene of apple may play
      a key role in the mechanism by which thyme essential oil effectively inhibits
      gray mold in apple fruit.

PMID- 29360732
TI  - Crosstalk of PmCBFs and PmDAMs Based on the Changes of Phytohormones under
      Seasonal Cold Stress in the Stem of Prunus mume.
AB  - Plants facing the seasonal variations always need a growth restraining mechanism
      when temperatures turn down. C-repeat binding factor (CBF) genes work essentially
      in the cold perception. Despite lots of researches on CBFs, the multiple
      crosstalk is still interesting on their interaction with hormones and dormancy
      associated MADS (DAM) genes in the growth and dormancy control. Therefore, this
      study highlights roles of PmCBFs in cold-induced dormancy from different orgens.
      And a sense-response relationship between PmCBFs and PmDAMs is exhibited in this
      process, jointly regulated by six PmCBFs and PmDAM4-6. Meantime, GA3 and ABA
      showed negative and positive correlation with PmCBFs expression levels,
      respectively. We also find a high correlation between IAA and PmDAM1-3. Finally,
      we display the interaction mode of PmCBFs and PmDAMs, especially PmCBF1-PmDAM1.
      These results can disclose another view of molecular mechanism in plant growth
      between cold-response pathway and dormancy regulation together with genes and
      hormones.

PMID- 29360734
TI  - Preparation of a Sepia Melanin and Poly(ethylene-alt-maleic Anhydride) Hybrid
      Material as an Adsorbent for Water Purification.
AB  - Meeting the increasing demand of clean water requires the development of novel
      efficient adsorbent materials for the removal of organic pollutants. In this
      context the use of natural, renewable sources is of special relevance and sepia
      melanin, thanks to its ability to bind a variety of organic and inorganic
      species, has already attracted interest for water purification. Here we describe
      the synthesis of a material obtained by the combination of sepia melanin and
      poly(ethylene-alt-maleic anhydride) (P(E-alt-MA)). Compared to sepia melanin, the
      resulting hybrid displays a high and fast adsorption efficiency towards methylene
      blue (a common industrial dye) for a wide pH range (from pH 2 to 12) and under
      high ionic strength conditions. It is easily recovered after use and can be
      reused up to three times. Given the wide availability of sepia melanin and P(E
      alt-MA), the synthesis of our hybrid is simple and affordable, making it suitable
      for industrial water purification purposes.

PMID- 29360733
TI  - Maternal Vitamin D Status and Infant Infection.
AB  - Maternal vitamin D status during pregnancy may modulate fetal immune system
      development and infant susceptibility to infections. Vitamin D deficiency is
      common during pregnancy, particularly among African American (AA) women. Our
      objective was to compare maternal vitamin D status (plasma 25(OH)D concentration)
      during pregnancy and first-year infections in the offspring of African American
      (AA) and non-AA women. We used medical records to record frequency and type of
      infections during the first year of life of 220 term infants (69 AA, 151 non-AA)
      whose mothers participated in the Kansas University DHA Outcomes Study. AA and
      non-AA groups were compared for maternal 25(OH)D by Mann-Whitney U-test. Compared
      to non-AA women, AA women were more likely to be vitamin D deficient (<50 nmol/L;
      84 vs. 37%, p < 0.001), and more of their infants had at least one infection in
      the first 6 months (78.3% and 59.6% of infants, respectively, p = 0.022). We next
      explored the relationship between maternal plasma 25(OH)D concentration and
      infant infections using Spearman correlations. Maternal 25(OH)D concentration was
      inversely correlated with the number of all infections (p = 0.033), eye, ear,
      nose, and throat (EENT) infections (p = 0.043), and skin infection (p = 0.021) in
      the first 6 months. A model that included maternal education, income, and 25(OH)D
      identified maternal education as the only significant predictor of infection risk
      in the first 6 months (p = 0.045); however, maternal education, income, and
      25(OH)D were all significantly lower in AA women compared to non-AA women . The
      high degree of correlation between these variables does not allow determination
      of which factor is driving the risk of infection; however, the one that is most
      easily remediated is vitamin D status. It would be of value to learn if vitamin D
      supplementation in this at-risk group could ameliorate at least part of the
      increased infection risk.

PMID- 29360735
TI  - The Critical Role of Thioacetamide Concentration in the Formation of ZnO/ZnS
      Heterostructures by Sol-Gel Process.
AB  - ZnO/ZnS heterostructures have emerged as an attractive approach for tailoring the
      properties of particles comprising these semiconductors. They can be synthesized
      using low temperature sol-gel routes. The present work yields insight into the
      mechanisms involved in the formation of ZnO/ZnS nanostructures. ZnO colloidal
      suspensions, prepared by hydrolysis and condensation of a Zn acetate precursor
      solution, were allowed to react with an ethanolic thioacetamide solution (TAA) as
      sulfur source. The reactions were monitored in situ by Small Angle X-ray
      Scattering (SAXS) and UV-vis spectroscopy, and the final colloidal suspensions
      were characterized by High Resolution Transmission Electron Microscopy (HRTEM).
      The powders extracted at the end of the reactions were analyzed by X-ray
      Absorption spectroscopy (XAS) and X-ray diffraction (XRD). Depending on TAA
      concentration, different nanostructures were revealed. ZnO and ZnS phases were
      mainly obtained at low and high TAA concentrations, respectively. At intermediate
      TAA concentrations, we evidenced the formation of ZnO/ZnS heterostructures. ZnS
      formation could take place via direct crystal growth involving Zn ions remaining
      in solution and S ions provided by TAA and/or chemical conversion of ZnO to ZnS.
      The combination of all the characterization techniques was crucial to elucidate
      the reaction steps and the nature of the final products.

PMID- 29360736
TI  - Demographic and Urbanization Disparities of Liver Transplantation in Taiwan.
AB  - Limited access to or receipt of liver transplantation (LT) may jeopardize
      survival of patients with end-stage liver diseases. Taiwan launched its National
      Health Insurance (NHI) program in 1995, which essentially removes financial
      barriers to health care. This study aims to investigate where there are still
      demographic and urbanization disparities of LT after 15 years of NHI program
      implementation. Data analyzed in this study were retrieved from Taiwan's NHI
      inpatient claims. A total of 3020 people aged >=18 years received LT between 2000
      and 2013. We calculated crude and adjusted prevalence rate of LT according to
      secular year, age, sex, and urbanization. The multiple Poisson regression model
      was further employed to assess the independent effects of demographics and
      urbanization on prevalence of LT. The biennial number of people receiving LT
      substantially increased from 56 in 2000-2001 to 880 in 2012-2013, representing a
      prevalence rate of 1.63 and 18.58 per 106, respectively. Such increasing secular
      trend was independent of sex. The prevalence was consistently higher in men than
      in women. The prevalence also increased with age in people <65 years, but dropped
      sharply in the elderly (>=65 years) people. We noted a significant disparity of
      LT in areas with different levels of urbanization. Compared to urban areas,
      satellite (prevalence rate ratio (PRR), 0.63, 95% confidence interval (CI), 0.57
      0.69) and rural (PRR, 0.76, 95% CI, 0.69-0.83) areas were both associated with a
      significantly lower prevalence of LT. There are still significant demographic and
      urbanization disparities in LT after 15 years of NHI program implementation.
      Given the predominance of living donor liver transplantation in Taiwan, further
      studies should be conducted to investigate factors associated with having a
      potential living donor for LT.

PMID- 29360737
TI  - Lasiodiplodia theobromae as a Producer of Biotechnologically Relevant Enzymes.
AB  - Phytopathogenic fungi are known to produce several types of enzymes usually
      involved in plant cell wall degradation and pathogenesis. The increasing of
      global temperature may induce fungi, such as Lasiodiplodia theobromae (L.
      theobromae), to alter its behavior. Nonetheless, there is only limited
      information regarding the effect of temperature on L. theobromae production of
      enzymes. The need for new, thermostable enzymes, that are biotechnologically
      relevant, led us to investigate the effect of temperature on the production of
      several extracellular enzymatic activities by different L. theobromae strains.
      Fungi were grown at 25  degrees C, 30  degrees C and 37  degrees C and the
      enzymatic activities were detected by plate assays, quantified by
      spectrophotometric methods and characterized by zymography. The thermostability
      (25-80  degrees C) of the enzymes produced was also tested. Strains CAA019,
      CBS339.90, LA-SOL3, LA-SV1 and LA-MA-1 produced amylases, gelatinases,
      caseinases, cellulases, lipases, laccases, xylanases, pectinases and pectin
      liases. Temperature modulated the expression of the enzymes, and this effect was
      more visible when fungi were grown at 37  degrees C than at lower temperatures.
      Contrary to proteolytic and endoglucanolytic activities, whose highest activities
      were detected when fungi were grown at 30  degrees C, lipolytic activity was not
      detected at this growth temperature. Profiles of proteases and endoglucanases of
      fungi grown at different temperatures were characterized by zymography. Enzymes
      were shown to be more thermostable when fungi were grown at 30  degrees C.
      Proteases were active up to 50  degrees C and endoglucanases up to 70  degrees C.
      Lipases were the least stable, with activities detected up to 45  degrees C. The
      enzymatic profiles detected for L. theobromae strains tested showed to be
      temperature and strain-dependent, making this species a good target for
      biotechnological applications.

PMID- 29360738
TI  - The Association between Air Pollution and Outpatient and Inpatient Visits in
      Shenzhen, China.
AB  - Nowadays, air pollution is a severe environmental problem in China. To
      investigate the effects of ambient air pollution on health, a time series
      analysis of daily outpatient and inpatient visits in 2015 were conducted in
      Shenzhen (China). Generalized additive model was employed to analyze associations
      between six air pollutants (namely SO2, CO, NO2, O3, PM10, and PM2.5) and daily
      outpatient and inpatient visits after adjusting confounding meteorological
      factors, time and day of the week effects. Significant associations between air
      pollutants and two types of hospital visits were observed. The estimated increase
      in overall outpatient visits associated with each 10 ug/m3 increase in air
      pollutant concentration ranged from 0.48% (O3 at lag 2) to 11.48% (SO2 with 2-day
      moving average); for overall inpatient visits ranged from 0.73% (O3 at lag 7) to
      17.13% (SO2 with 8-day moving average). Our results also suggested a
      heterogeneity of the health effects across different outcomes and in different
      populations. The findings in present study indicate that even in Shenzhen, a less
      polluted area in China, significant associations exist between air pollution and
      daily number of overall outpatient and inpatient visits.

PMID- 29360739
TI  - Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by
      Suppressing Sphingosine Metabolic Pathway In Vitro.
AB  - Hepatocellular carcinoma (HCC) frequently develops from hepatitis C virus (HCV)
      and hepatitis B virus (HBV) infection. We previously reported that peretinoin, an
      acyclic retinoid, inhibits HCV replication. This study aimed to examine the
      influence of peretinoin on the HBV lifecycle. HBV-DNA and covalently closed
      circular DNA (cccDNA) were evaluated by a qPCR method in HepG2.2.15 cells.
      Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear
      cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity.
      Conversely, other retinoids, such as 9-cis, 13-cis retinoic acid (RA), and all
      trans-retinoic acid (ATRA), had no effect or rather increased HBV replication.
      Mechanistically, although peretinoin increased the expression of HBV-related
      transcription factors, as observed for other retinoids, peretinoin enhanced the
      binding of histone deacetylase 1 (HDAC1) to cccDNA in the nucleus and negatively
      regulated HBV transcription. Moreover, peretinoin significantly inhibited the
      expression of SPHK1, a potential inhibitor of HDAC activity, and might be
      involved in hepatic inflammation, fibrosis, and HCC. SPHK1 overexpression in
      cells cancelled the inhibition of HBV replication induced by peretinoin. This
      indicates that peretinoin activates HDAC1 and thereby suppresses HBV replication
      by inhibiting the sphingosine metabolic pathway. Therefore, peretinoin may be a
      novel therapeutic agent for HBV replication and chemoprevention against HCC.

PMID- 29360741
TI  - A Patient-Centered Approach to Guide Follow-Up and Adjunctive Testing and
      Treatment after First Rib Resection for Venous Thoracic Outlet Syndrome Is Safe
      and Effective.
AB  - Controversies in the treatment of venous thoracic outlet syndrome (VTOS) have
      been discussed for decades, but still persist. Calls for more objective reporting
      standards have pushed practice towards comprehensive venous evaluations and
      interventions after first rib resection (FRR) for all patients. In our practice,
      we have relied on patient-centered, patient-reported outcomes to guide adjunctive
      treatment and measure success. Thus, we sought to investigate the use of
      thrombolysis versus anticoagulation alone, timing of FRR following thrombolysis,
      post-FRR venous intervention, and FRR for McCleery syndrome (MCS) and their
      impact on patient symptoms and return to function. All patients undergoing FRR
      for VTOS at our institution from 4 April 2000 through 31 December 2013 were
      reviewed. Demographics, symptoms, diagnostic and treatment details, and outcomes
      were collected. Per "Reporting Standards of the Society for Vascular Surgery for
      Thoracic Outlet Syndrome", symptoms were described as
      swelling/discoloration/heaviness, collaterals, concomitant neurogenic symptoms,
      and functional impairment. Patient-reported response to treatment was defined as
      complete (no residual symptoms and return to function), partial (any residual
      symptoms present but no functional impairment), temporary (initial improvement
      but subsequent recurrence of any symptoms or functional impairment), or none
      (persistent symptoms or functional impairment). Sixty FRR were performed on 59
      patients. 54.2% were female with a mean age of 34.3 years.
      Swelling/discoloration/heaviness was present in all but one patient, deep vein
      thrombosis in 80%, and visible collaterals in 41.7%. Four patients had pulmonary
      embolus while 65% had concomitant neurogenic symptoms. In addition, 74.6% of
      patients were anticoagulated and 44.1% also underwent thrombolysis prior to FRR.
      Complete or partial response occurred in 93.4%. Of the four patients with
      temporary or no response, further diagnostics revealed residual venous disease in
      two and occult alternative diagnoses in two. Use of thrombolysis was not related
      to FRR outcomes (p = 0.600). Performance of FRR less than or greater than six
      weeks after the initiation of anticoagulation or treatment with thrombolysis was
      not related to FRR outcomes (p = 1). Whether patients had DVT or MCS was not
      related to FRR outcomes (p = 1). No patient had recurrent DVT. From a patient
      centered, patient-reported standpoint, VTOS is equally effectively treated with
      FRR regardless of preoperative thrombolysis or timing of surgery after
      thrombolysis. A conservative approach to venous interrogation and intervention
      after FRR is safe and effective for symptom control and return to function.
      Additionally, patients with MCS are effectively treated with FRR.

PMID- 29360740
TI  - Proteomic Analysis of Methanonatronarchaeum thermophilum AMET1, a Representative
      of a Putative New Class of Euryarchaeota, "Methanonatronarchaeia".
AB  - The recently discovered Methanonatronarchaeia are extremely halophilic and
      moderately thermophilic methyl-reducing methanogens representing a novel class
      level lineage in the phylum Euryarchaeota related to the class Halobacteria. Here
      we present a detailed analysis of 1D-nano liquid chromatography-electrospray
      ionization tandem mass spectrometry data obtained for "Methanonatronarchaeum
      thermophilum" AMET1 grown in different physiological conditions, including
      variation of the growth temperature and substrates. Analysis of these data allows
      us to refine the current understanding of the key biosynthetic pathways of this
      triple extremophilic methanogenic euryarchaeon and identify proteins that are
      likely to be involved in its response to growth condition changes.

PMID- 29360742
TI  - Vaccinia virus in Feces and Urine of Wild Rodents from Sao Paulo State, Brazil.
AB  - The origin of Vaccinia virus (VACV) outbreaks in Brazil remains unknown, but
      since the isolation of VACV in Mus musculus mice during a zoonotic outbreak
      affecting cattle and milkers, peridomestic rodents have been suggested to be a
      link between cows and wild animals. Considering that experimentally infected mice
      eliminate viral particles in their feces, we investigated the presence of VACV in
      the feces and urine of wild rodents that were captured in the forest areas
      surrounding milking farms in the central west region of Sao Paulo State. For the
      first time, this work reports the detection of VACV by PCR in the feces of
      naturally infected Oligoryzomys flavescens, Oligoryzomys nigripes, and Sooretamys
      angouya, and in the urine of Oligorizomys flavescens, which raises important
      questions about the spread of VACV by rodent feces and its potential to induce
      clinical infections in cows.

PMID- 29360743
TI  - System-Wide and Group-Specific Health Service Improvements: Cross-Sectional
      Survey of Outpatient Improvement Preferences and Associations with Demographic
      Characteristics.
AB  - Efficient patient-centred quality improvement requires an understanding of the
      system-wide areas of dissatisfaction along with evidence to identify the programs
      which can be strategically targeted according to specific patient characteristics
      and preferences. This cross-sectional study reports the proportion of chronic
      disease outpatients selecting 23 patient-centred improvement initiatives. Using
      univariate tests and multivariable logistic regressions, this multi-site study
      also identifies initiatives differentially selected by outpatients according to
      clinical and demographic characteristics. A total of 475 outpatients participated
      (49% response). Commonly selected initiatives included: reducing wait-times
      (22.3%); convenient appointment scheduling (16.0%); and receiving up-to-date
      treatment information (16.0%). Within univariate tests, preferences for
      information and service accessibility initiatives were not significantly
      associated with specific subgroups. However, seven initiatives were preferred
      according to age, gender, diagnosis status, and chronic disease type within
      multivariate models. For example, neurology outpatients were more likely to
      select assistance to manage psychological symptoms when compared to oncology
      outpatients (OR: 2.89). Study findings suggest that system-wide programs to
      enhance information provision are strategic approaches to improve experiences
      across patient characteristics. Furthermore, a few initiatives can be targeted to
      specific groups and emphasized the importance of detailed scoping analyses and
      tailored implementation plans when designing patient-centred quality improvement
      programs.

PMID- 29360744
TI  - Melanins in Fossil Animals: Is It Possible to Infer Life History Traits from the
      Coloration of Extinct Species?
AB  - Paleo-colour scientists have recently made the transition from describing melanin
      based colouration in fossil specimens to inferring life-history traits of the
      species involved. Two such cases correspond to counter-shaded dinosaurs: dark
      coloured due to melanins dorsally, and light-coloured ventrally. We believe that
      colour reconstruction of fossils based on the shape of preserved microstructures
      the majority of paleo-colour studies involve melanin granules-is not without
      risks. In addition, animals with contrasting dorso-ventral colouration may be
      under different selection pressures beyond the need for camouflage, including,
      for instance, visual communication or ultraviolet (UV) protection. Melanin
      production is costly, and animals may invest less in areas of the integument
      where pigments are less needed. In addition, melanocytes exposed to UV radiation
      produce more melanin than unexposed melanocytes. Pigment economization may thus
      explain the colour pattern of some counter-shaded animals, including extinct
      species. Even in well-studied extant species, their diversity of hues and
      patterns is far from being understood; inferring colours and their functions in
      species only known from one or few specimens from the fossil record should be
      exerted with special prudence.

PMID- 29360745
TI  - GC-MS Metabolomics to Evaluate the Composition of Plant Cuticular Waxes for Four
      Triticum aestivum Cultivars.
AB  - Wheat (Triticum aestivum L.) is an important food crop, and biotic and abiotic
      stresses significantly impact grain yield. Wheat leaf and stem surface waxes are
      associated with traits of biological importance, including stress resistance.
      Past studies have characterized the composition of wheat cuticular waxes, however
      protocols can be relatively low-throughput and narrow in the range of metabolites
      detected. Here, gas chromatography-mass spectrometry (GC-MS) metabolomics methods
      were utilized to provide a comprehensive characterization of the chemical
      composition of cuticular waxes in wheat leaves and stems. Further, waxes from
      four wheat cultivars were assayed to evaluate the potential for GC-MS
      metabolomics to describe wax composition attributed to differences in wheat
      genotype. A total of 263 putative compounds were detected and included 58 wax
      compounds that can be classified (e.g., alkanes and fatty acids). Many of the
      detected wax metabolites have known associations to important biological
      functions. Principal component analysis and ANOVA were used to evaluate
      metabolite distribution, which was attributed to both tissue type (leaf, stem)
      and cultivar differences. Leaves contained more primary alcohols than stems such
      as 6-methylheptacosan-1-ol and octacosan-1-ol. The metabolite data were validated
      using scanning electron microscopy of epicuticular wax crystals which detected
      wax tubules and platelets. Conan was the only cultivar to display alcohol
      associated platelet-shaped crystals on its abaxial leaf surface. Taken together,
      application of GC-MS metabolomics enabled the characterization of cuticular wax
      content in wheat tissues and provided relative quantitative comparisons among
      sample types, thus contributing to the understanding of wax composition
      associated with important phenotypic traits in a major crop.

PMID- 29360746
TI  - Comparative Genomics of the Balsaminaceae Sister Genera Hydrocera triflora and
      Impatiens pinfanensis.
AB  - The family Balsaminaceae, which consists of the economically important genus
      Impatiens and the monotypic genus Hydrocera, lacks a reported or published
      complete chloroplast genome sequence. Therefore, chloroplast genome sequences of
      the two sister genera are significant to give insight into the phylogenetic
      position and understanding the evolution of the Balsaminaceae family among the
      Ericales. In this study, complete chloroplast (cp) genomes of Impatiens
      pinfanensis and Hydrocera triflora were characterized and assembled using a high
      throughput sequencing method. The complete cp genomes were found to possess the
      typical quadripartite structure of land plants chloroplast genomes with double
      stranded molecules of 154,189 bp (Impatiens pinfanensis) and 152,238 bp
      (Hydrocera triflora) in length. A total of 115 unique genes were identified in
      both genomes, of which 80 are protein-coding genes, 31 are distinct transfer RNA
      (tRNA) and four distinct ribosomal RNA (rRNA). Thirty codons, of which 29 had A/T
      ending codons, revealed relative synonymous codon usage values of >1, whereas
      those with G/C ending codons displayed values of <1. The simple sequence repeats
      comprise mostly the mononucleotide repeats A/T in all examined cp genomes.
      Phylogenetic analysis based on 51 common protein-coding genes indicated that the
      Balsaminaceae family formed a lineage with Ebenaceae together with all the other
      Ericales.

PMID- 29360747
TI  - Groundwater Arsenic Contamination in the Ganga River Basin: A Future Health
      Danger.
AB  - This study highlights the severity of arsenic contamination in the Ganga River
      basin (GRB), which encompasses significant geographic portions of India,
      Bangladesh, Nepal, and Tibet. The entire GRB experiences elevated levels of
      arsenic in the groundwater (up to 4730 ug/L), irrigation water (~1000 ug/L), and
      in food materials (up to 3947 ug/kg), all exceeding the World Health
      Organization's standards for drinking water, the United Nations Food and
      Agricultural Organization's standard for irrigation water (100 ug/L), and the
      Chinese Ministry of Health's standard for food in South Asia (0.15 mg/kg),
      respectively. Several individuals demonstrated dermal, neurological,
      reproductive, cognitive, and cancerous effects; many children have been diagnosed
      with a range of arsenicosis symptoms, and numerous arsenic-induced deaths of
      youthful victims are reported in the GRB. Victims of arsenic exposure face
      critical social challenges in the form of social isolation and hatred by their
      respective communities. Reluctance to establish arsenic standards and
      unsustainable arsenic mitigation programs have aggravated the arsenic calamity in
      the GRB and put millions of lives in danger. This alarming situation resembles a
      ticking time bomb. We feel that after 29 years of arsenic research in the GRB, we
      have seen the tip of the iceberg with respect to the actual magnitude of the
      catastrophe; thus, a reduced arsenic standard for drinking water, testing all
      available drinking water sources, and sustainable and cost-effective arsenic
      mitigation programs that include the participation of the people are urgently
      needed.

PMID- 29360748
TI  - Role of Disulfide Bonds in Activity and Stability of Tigerinin-1R.
AB  - Tigerinin-1R (Arg-Val-Cys-Ser-Ala-Ile-Pro-Leu-Pro-Ile-Cys-His-NH2), a cationic 12
      mer peptide containing a disulfide bond extracted from frog skin secretions,
      lacks antibacterial activity, but has the ability to stimulate insulin release
      both in vitro and in vivo. To study the structure-function relationships of
      tigerinin-1R, we designed and synthesized five analogs, including tigerinin
      cyclic, tigerinin-1R-L4, tigerinin-linear, [C3K]tigerinin-1R, and [C11K]tigerinin
      1R. Tigerinin-1R promoted insulin secretion in a concentration-dependent manner
      in INS-1 cells without obvious cytotoxicity. At a concentration of 10-5 M,
      [C11K]tigerinin-1R exhibited the highest stimulation ability, suggesting that the
      positive charge at the C-terminus may contribute to the in vitro insulin
      releasing activity of tigerinin-1R. Tigerinin-1R peptides stimulated insulin
      release in INS-1 cells through a universal mechanism that involves mobilization
      of intracellular calcium without disrupting the cell membrane. In vivo
      experiments showed that both tigerinin-1R and [C11K]tigerinin-1R improved glucose
      tolerance in overnight-fasted mice. Due to its structural stability, tigerinin-1R
      showed superior hypoglycemic activity to [C11K]tigerinin-1R, which suggested a
      critical role of the disulfide bonds. In addition, we also identified a
      protective effect of tigerinin-1R peptides in apoptosis induced by oxidative
      stress. These results further confirm the potential for the development of
      tigerinin-1R as an anti-diabetic therapeutic agent in clinical practice.

PMID- 29360749
TI  - Impact Analysis of Temperature and Humidity Conditions on Electrochemical Sensor
      Response in Ambient Air Quality Monitoring.
AB  - The increasing applications of low-cost air sensors promises more convenient and
      cost-effective systems for air monitoring in many places and under many
      conditions. However, the data quality from such systems has not been fully
      characterized and may not meet user expectations in research and regulatory uses,
      or for use in citizen science. In our study, electrochemical sensors (Alphasense
      B4 series) for carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2),
      and oxidants (Ox) were evaluated under controlled laboratory conditions to
      identify the influencing factors and quantify their relation with sensor outputs.
      Based on the laboratory tests, we developed different correction methods to
      compensate for the impact of ambient conditions. Further, the sensors were
      assembled into a monitoring system and tested in ambient conditions in Hong Kong
      side-by-side with regulatory reference monitors, and data from these tests were
      used to evaluate the performance of the models, to refine them, and validate
      their applicability in variable ambient conditions in the field. The more
      comprehensive correction models demonstrated enhanced performance when compared
      with uncorrected data. One over-arching observation of this study is that the low
      cost sensors may promise excellent sensitivity and performance, but it is
      essential for users to understand and account for several key factors that may
      strongly affect the nature of sensor data. In this paper, we also evaluated
      factors of multi-month stability, temperature, and humidity, and considered the
      interaction of oxidant gases NO2 and ozone on a newly introduced oxidant sensor.

PMID- 29360750
TI  - Proteomic Analysis of Secretomes of Oncolytic Herpes Simplex Virus-Infected
      Squamous Cell Carcinoma Cells.
AB  - Oncolytic herpes simplex virus type 1 (HSV-1) strain RH2 induced immunogenic cell
      death (ICD) with the release and surface exposure of damage-associated molecular
      patterns (DAMPs) in squamous cell carcinoma (SCC) SCCVII cells. The supernatants
      of RH2-infected SCCVII cells also exhibited antitumor ability by intratumoral
      administration in SCCVII tumor-bearing mice. The supernatants of RH2-infected
      cells and mock-infected cells were concentrated to produce Med24 and MedC for
      proteomic analyses. In Med24, the up- and down-regulated proteins were observed.
      Proteins including filamin, tubulin, t-complex protein 1 (TCP-1), and heat shock
      proteins (HSPs), were up-regulated, while extracellular matrix (ECM) proteins
      were markedly down-regulated. Viral proteins were detected in Med 24. These
      results indicate that HSV-1 RH2 infection increases the release of danger signal
      proteins and viral gene products, but decreases the release of ECM components.
      These changes may alter the tumor microenvironment (TME) and contribute to
      enhancement of anti-tumor immunity against SCC.

PMID- 29360752
TI  - Mesenchymal Stem Cells Derived from Healthy and Diseased Human Gingiva Support
      Osteogenesis on Electrospun Polycaprolactone Scaffolds.
AB  - Periodontitis is a chronic inflammatory disease affecting almost half of the
      adult US population. Gingiva is an integral part of the periodontium and has
      recently been identified as a source of adult gingiva-derived mesenchymal stem
      cells (GMSCs). Given the prevalence of periodontitis, the purpose of this study
      is to evaluate differences between GMSCs derived from healthy and diseased
      gingival tissues and explore their potential in bone engineering. Primary clonal
      cell lines were established from harvested healthy and diseased gingival and
      characterized for expression of known stem-cell markers and multi-lineage
      differentiation potential. Finally, they were cultured on electrospun
      polycaprolactone (PCL) scaffolds and evaluated for attachment, proliferation, and
      differentiation. Flow cytometry demonstrated cells isolated from healthy and
      diseased gingiva met the criteria defining mesenchymal stem cells (MSCs).
      However, GMSCs from diseased tissue showed decreased colony-forming unit
      efficiency, decreased alkaline phosphatase activity, weaker osteoblast
      mineralization, and greater propensity to differentiate into adipocytes than
      their healthy counterparts. When cultured on electrospun PCL scaffolds, GMSCs
      from both sources showed robust attachment and proliferation over a 7-day period;
      they exhibited high mineralization as well as strong expression of alkaline
      phosphatase. Our results show preservation of 'stemness' and osteogenic potential
      of GMSC even in the presence of disease, opening up the possibility of using
      routinely discarded, diseased gingival tissue as an alternate source of adult
      MSCs.

PMID- 29360751
TI  - Estrogenic Effects of the Extracts from the Chinese Yam (Dioscorea opposite
      Thunb.) and Its Effective Compounds in Vitro and in Vivo.
AB  - BACKGROUND: The aim of this study was to explore the estrogenic effects of the
      extracts from Chinese yam and its effective compounds. METHODS: The activity of
      the yam was investigated by the uterine weight gain of mice and a proliferation
      assay of breast cancer cell lines (MCF-7 cell); the estrogenic activity was
      comprehensively evaluated by a serum pharmacology experiment. The levels of
      estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH)
      were also measured. Western blot analysis and antagonist assays with faslodex
      (ICI182,780), methylpiperidino-pyrazole (MPP), Delta (9) -tetrahydrocannabinol
      (THC), and G-15 were used to explore the mechanism of the effects of the yam. To
      find the effective compounds of the yam which play a role in its estrogen-like
      effects, we used the same methods to study the effects of adenosine and arbutin.
      RESULTS: The Chinese yam and two main compounds, adenosine and arbutin, have
      estrogen-like effects. The mechanism of the yam which plays a role in its
      estrogen-like effects was mainly mediated by the estrogen receptors ERalpha,
      ERbeta, and GPR30; that of adenosine was mainly mediated by estrogen receptors
      ERalpha and ERbeta, and that of arbutin was mainly mediated by estrogen receptors
      ERbeta and GPR30. CONCLUSIONS: The Chinese yam has estrogen-like effects;
      adenosine and arbutin are two of the effective compounds in the yam which play a
      role in its estrogen-like effects.

PMID- 29360753
TI  - Global Metabolomics of the Placenta Reveals Distinct Metabolic Profiles between
      Maternal and Fetal Placental Tissues Following Delivery in Non-Labored Women.
AB  - We evaluated the metabolic alterations in maternal and fetal placental tissues
      from non-labored women undergoing cesarean section using samples collected from 5
      min to 24 h following delivery. Using 1H-NMR, we identified 14 metabolites that
      significantly differed between maternal and fetal placental tissues (FDR
      corrected p-value < 0.05), with 12 metabolites elevated in the maternal tissue,
      reflecting the flux of these metabolites from mother to fetus. In the maternal
      tissue, 4 metabolites were significantly altered at 15 min, 10 metabolites at 30
      min, and 16 metabolites at 1 h postdelivery, while 11 metabolites remained stable
      over 24 h. In contrast, in the fetal placenta tissue, 1 metabolite was
      significantly altered at 15 min, 2 metabolites at 30 min, and 4 metabolites at 1
      h postdelivery, while 22 metabolites remained stable over 24 h. Our study
      provides information on the metabolic profiles of maternal and fetal placental
      tissues delivered by cesarean section and reveals that there are different
      metabolic alterations in the maternal and fetal tissues of the placenta following
      delivery.

PMID- 29360754
TI  - Characterization of Different Cable Ferrite Materials to Reduce the
      Electromagnetic Noise in the 2-150 kHz Frequency Range.
AB  - The gap of standardization for conducted and field coupled electromagnetic
      interferences (EMI) in the 2-150 kHz frequency range can lead to Electromagnetic
      Compatibility (EMC) problems. This is caused by power systems such as Pulse Width
      Modulation (PWM) controlled rectifiers, photovoltaic inverters or charging
      battery units in electric vehicles. This is a very important frequency spectral
      due to interferences generated in a wide range of devices and, specifically,
      communication problems in the new technologies and devices incorporated to the
      traditional grid to convert it into a Smart Grid. Consequently, it is necessary
      to provide new solutions to attenuate this kind of interference, which involves
      finding new materials that are able to filter the electromagnetic noise. This
      contribution is focused on characterizing the performance of a novel material
      based on nanocrystalline and comparing it to most common material compositions
      such as MnZn and NiZn. This research is carried out from the point of view of the
      manufacturing process, magnetic properties and EMI suppression ability. This last
      item is carried out through two analysis procedures: a theoretical method by
      determining the attenuation ratio by measuring impedance parameter and proposing
      a new empirical technique based on measuring directly the insertion loss
      parameter. Therefore, the main aim of this characterization process is to
      determine the performance of nanocrystalline compared to traditional cable
      ferrite compositions to reduce the interferences in this controversial frequency
      range. From the results obtained, it is possible to deduce that nanocrystalline
      cable ferrite provides the best performance to filter the electromagnetic noise
      in the 2-150 kHz frequency range.

PMID- 29360756
TI  - Selective Blockade of the Metabotropic Glutamate Receptor mGluR5 Protects Mouse
      Livers in In Vitro and Ex Vivo Models of Ischemia Reperfusion Injury.
AB  - 2-Methyl-6-(phenylethynyl)pyridine (MPEP), a negative allosteric modulator of the
      metabotropic glutamate receptor (mGluR) 5, protects hepatocytes from ischemic
      injury. In astrocytes and microglia, MPEP depletes ATP. These findings seem to be
      self-contradictory, since ATP depletion is a fundamental stressor in ischemia.
      This study attempted to reconstruct the mechanism of MPEP-mediated ATP depletion
      and the consequences of ATP depletion on protection against ischemic injury. We
      compared the effects of MPEP and other mGluR5 negative modulators on ATP
      concentration when measured in rat hepatocytes and acellular solutions. We also
      evaluated the effects of mGluR5 blockade on viability in rat hepatocytes exposed
      to hypoxia. Furthermore, we studied the effects of MPEP treatment on mouse livers
      subjected to cold ischemia and warm ischemia reperfusion. We found that MPEP and
      3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) deplete ATP in hepatocytes
      and acellular solutions, unlike fenobam. This finding suggests that mGluR5s may
      not be involved, contrary to previous reports. MPEP, as well as MTEP and fenobam,
      improved hypoxic hepatocyte viability, suggesting that protection against
      ischemic injury is independent of ATP depletion. Significantly, MPEP protected
      mouse livers in two different ex vivo models of ischemia reperfusion injury,
      suggesting its possible protective deployment in the treatment of hepatic
      inflammatory conditions.

PMID- 29360755
TI  - Signaling by Steroid Hormones in the 3D Nuclear Space.
AB  - Initial studies showed that ligand-activated hormone receptors act by binding to
      the proximal promoters of individual target genes. Genome-wide studies have now
      revealed that regulation of transcription by steroid hormones mainly depends on
      binding of the receptors to distal regulatory elements. Those distal elements,
      either enhancers or silencers, act on the regulation of target genes by chromatin
      looping to the gene promoters. In the nucleus, this level of chromatin folding is
      integrated within dynamic higher orders of genome structures, which are organized
      in a non-random fashion. Terminally differentiated cells exhibit a tissue
      specific three-dimensional (3D) organization of the genome that favors or
      restrains the activity of transcription factors and modulates the function of
      steroid hormone receptors, which are transiently activated upon hormone exposure.
      Conversely, integration of the hormones signal may require modifications of the
      3D organization to allow appropriate transcriptional outcomes. In this review, we
      summarize the main levels of organization of the genome, review how they can
      modulate the response to steroids in a cell specific manner and discuss the role
      of receptors in shaping and rewiring the structure in response to hormone. Taking
      into account the dynamics of 3D genome organization will contribute to a better
      understanding of the pleiotropic effects of steroid hormones in normal and cancer
      cells.

PMID- 29360757
TI  - Genome-Wide Characterization of Heat-Shock Protein 70s from Chenopodium quinoa
      and Expression Analyses of Cqhsp70s in Response to Drought Stress.
AB  - Heat-shock proteins (HSPs) are ubiquitous proteins with important roles in
      response to biotic and abiotic stress. The 70-kDa heat-shock genes (Hsp70s)
      encode a group of conserved chaperone proteins that play central roles in
      cellular networks of molecular chaperones and folding catalysts across all the
      studied organisms including bacteria, plants and animals. Several Hsp70s involved
      in drought tolerance have been well characterized in various plants, whereas no
      research on Chenopodium quinoa HSPs has been completed. Here, we analyzed the
      genome of C. quinoa and identified sixteen Hsp70 members in quinoa genome.
      Phylogenetic analysis revealed the independent origination of those Hsp70
      members, with eight paralogous pairs comprising the Hsp70 family in quinoa. While
      the gene structure and motif analysis showed high conservation of those
      paralogous pairs, the synteny analysis of those paralogous pairs provided
      evidence for expansion coming from the polyploidy event. With several subcellular
      localization signals detected in CqHSP70 protein paralogous pairs, some of the
      paralogous proteins lost the localization information, indicating the diversity
      of both subcellular localizations and potential functionalities of those HSP70s.
      Further gene expression analyses revealed by quantitative polymerase chain
      reaction (qPCR) analysis illustrated the significant variations of Cqhsp70s in
      response to drought stress. In conclusion, the sixteen Cqhsp70s undergo lineage
      specific expansions and might play important and varied roles in response to
      drought stress.

PMID- 29360758
TI  - Fabrication of Two Polyester Nanofiber Types Containing the Biobased Monomer
      Isosorbide: Poly (Ethylene Glycol 1,4-Cyclohexane Dimethylene Isosorbide
      Terephthalate) and Poly (1,4-Cyclohexane Dimethylene Isosorbide Terephthalate).
AB  - The thermal and mechanical properties of two types of polyester nanofiber, poly
      (1,4-cyclohexanedimethylene isosorbide terephthalate) (PICT) copolymers and the
      terpolyester of isosorbide, ethylene glycol, 1,4-cyclohexane dimethanol, and
      terephthalic acid (PEICT), were investigated. This is the first attempt to
      fabricate PICT nanofiber via the electrospinning method; comparison with PEICT
      nanofiber could give greater understanding of eco-friendly nanofibers containing
      biomass monomers. The nanofibers fabricated from each polymer show similar smooth
      and thin-and-long morphologies. On the other hand, the polymers exhibited
      significantly different mechanical and thermal properties; in particular, a
      higher tensile strength was observed for PICT nanofiber mat than for that of
      PEICT. We hypothesized that PICT has more trans-configuration than PEICT,
      resulting in enhancement of its tensile strength, and demonstrated this by
      Fourier transform infrared spectroscopy. In addition, PICT nanofibers showed
      clear crystallization behavior upon increased temperature, while PEICT nanofibers
      showed completely amorphous structure. Both nanofibers have better tensile
      properties and thermal stability than the typical polyester polymer, implying
      that they can be utilized in various industrial applications.

PMID- 29360759
TI  - A Computational Approach for Understanding the Interactions between Graphene
      Oxide and Nucleoside Diphosphate Kinase with Implications for Heart Failure.
AB  - During a heart failure, an increased content and activity of nucleoside
      diphosphate kinase (NDPK) in the sarcolemmal membrane is responsible for
      suppressing the formation of the second messenger cyclic adenosine monophosphate
      (cAMP)-a key component required for calcium ion homeostasis for the proper
      systolic and diastolic functions. Typically, this increased NDPK content lets the
      surplus NDPK react with a mutated G protein in the beta-adrenergic signal
      transduction pathway, thereby inhibiting cAMP synthesis. Thus, it is thus that
      inhibition of NDPK may cause a substantial increase in adenylate cyclase
      activity, which in turn may be a potential therapy for end-stage heart failure
      patients. However, there is little information available about the molecular
      events at the interface of NDPK and any prospective molecule that may potentially
      influence its reactive site (His118). Here we report a novel computational
      approach for understanding the interactions between graphene oxide (GO) and NDPK.
      Using molecular dynamics, it is found that GO interacts favorably with the His118
      residue of NDPK to potentially prevent its binding with adenosine triphosphate
      (ATP), which otherwise would trigger the phosphorylation of the mutated G
      protein. Therefore, this will result in an increase in cAMP levels during heart
      failure.

PMID- 29360760
TI  - Regulation of Akt/FoxO3a/Skp2 Axis Is Critically Involved in Berberine-Induced
      Cell Cycle Arrest in Hepatocellular Carcinoma Cells.
AB  - The maintenance of ordinal cell cycle phases is a critical biological process in
      cancer genesis, which is a crucial target for anti-cancer drugs. As an important
      natural isoquinoline alkaloid from Chinese herbal medicine, Berberine (BBR) has
      been reported to possess anti-cancer potentiality to induce cell cycle arrest in
      hepatocellular carcinoma cells (HCC). However, the underlying mechanism remains
      to be elucidated. In our present study, G0/G1 phase cell cycle arrest was
      observed in berberine-treated Huh-7 and HepG2 cells. Mechanically, we observed
      that BBR could deactivate the Akt pathway, which consequently suppressed the S
      phase kinase-associated protein 2 (Skp2) expression and enhanced the expression
      and translocation of Forkhead box O3a (FoxO3a) into nucleus. The translocated
      FoxO3a on one hand could directly promote the transcription of cyclin-dependent
      kinase inhibitors (CDKIs) p21Cip1 and p27Kip1, on the other hand, it could
      repress Skp2 expression, both of which lead to up-regulation of p21Cip1 and
      p27Kip1, causing G0/G1 phase cell cycle arrest in HCC. In conclusion, BBR
      promotes the expression of CDKIs p21Cip1 and p27Kip1 via regulating the
      Akt/FoxO3a/Skp2 axis and further induces HCC G0/G1 phase cell cycle arrest. This
      research uncovered a new mechanism of an anti-cancer effect of BBR.

PMID- 29360761
TI  - A Novel Approach to Transforming Smoking Cessation Practice for Pregnant
      Aboriginal Women and Girls Living in the Pilbara.
AB  - Tobacco smoking during pregnancy contributes to a range of adverse perinatal
      outcomes; but is a potentially modifiable behavior. In Australia Aboriginal and
      Torres Strait Islander women face a range of barriers that hinder; rather than
      support smoking cessation. Few smoking cessation programs consider the broader
      social determinants of women's lives; the gendered nature of these or the
      complexities which impinge on behavior change in the presence of social and
      economic disadvantage and substantial individual and intergenerational trauma.
      Drawing on the salient gender and trauma-informed literature this paper describes
      the rationale underpinning formative research which will inform the design of a
      localized, culturally meaningful smoking cessation program for Aboriginal women
      living in the Hedland and Western Desert communities of the remote Pilbara region
      of Western Australia. We contend that a women-centered, trauma-informed approach
      to smoking cessation has much to offer those seeking to address this critical
      public health issue.

PMID- 29360762
TI  - Protective Effect of Meretrix meretrix Oligopeptides on High-Fat-Diet-Induced Non
      Alcoholic Fatty Liver Disease in Mice.
AB  - The present study investigated the effects of MMO (Meretrix meretrix
      oligopeptides) on mice fed a high-fat diet. Mice were fed either a normal control
      diet (NC) or a high-fat diet (HFD) without or with MMO (50 mg/kg or 250 mg/kg)
      for four weeks. Levels of ALT, AST, liver tissue GSH-Px, and SOD activities, MDA
      levels were measured using commercially available kits; HE staining was performed
      to analyze pathologic changes of the liver; a TEM assay was performed to measure
      the ultrastructural alterations of the mitochondria, and Western blotting was
      performed to detect the expression of gene proteins related to lipid metabolism,
      inflammation, and liver apoptosis. After six weeks, body weight, ALT, AST, and
      MDA levels were significantly increased, and GSH-Px levels and SOD activities
      were significantly decreased in the HFD control group compared with the NC group.
      Consumption of the HFD compared with the NC caused fatty liver abnormal
      mitochondria with loss of cristae, intramitochondrial granules, and a swollen and
      rarefied matrix. Administration of MMO significantly decreased body weight gain,
      and ALT, AST, and MDA levels; increased SOD activity and GSH-Px levels;
      alleviated fatty liver steatosis; decreased the early apoptosis population;
      downregulated SREBP-1c, Bax, Caspase-9, Caspase-3, TNF-alpha, and NF-kappaB
      protein levels; and upregulated PPAR-alpha, Bcl-2, and AMPK-alpha, compared with
      the HFD control group. MMO exhibited protective effects in mice with NAFLD by
      regulating the NF-kappaB anti-inflammation signaling pathways to inhibit
      inflammation, regulate AMPK-alpha, PPAR-alpha and SREBP-1c to improve lipid
      metabolism disorder, and regulate Bcl-2/Bax anti-apoptosis signaling pathways to
      prevent liver cell apoptosis. These results suggest that dietary supplementation
      with MMO ameliorates high-fat-diet-induced NAFLD.

PMID- 29360763
TI  - Microstructural Evolution and Phase Formation in 2nd-Generation Refractory-Based
      High Entropy Alloys.
AB  - Refractory-based high entropy alloys (HEAs) of the 2nd-generation type are new
      intensively-studied materials with a high potential for structural high
      temperature applications. This paper presents investigation results on
      microstructural evolution and phase formation in as-cast and subsequently heat
      treated HEAs at various temperature-time regimes. Microstructural examination was
      performed by means of scanning electron microscopy (SEM) combined with the energy
      dispersive spectroscopy (EDS) mode of electron probe microanalysis (EPMA) and
      qualitative X-ray diffraction (XRD). The primary evolutionary trend observed was
      the tendency of Zr to gradually segregate as the temperature rises, while all the
      other elements eventually dissolve in the BCC solid solution phase once the onset
      of Laves phase complex decomposition is reached. The performed thermodynamic
      modelling was based on the Calculation of Phase Diagrams method (CALPHAD). The
      BCC A2 solid solution phase is predicted by the model to contain increasing
      amounts of Cr as the temperature rises, which is in perfect agreement with the
      actual results obtained by SEM. However, the model was not able to predict the
      existence of the Zr-rich phase or the tendency of Zr to segregate and form its
      own solid solution-most likely as a result of the Zr segregation trend not being
      an equilibrium phenomenon.

PMID- 29360764
TI  - Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review.
AB  - Several earlier studies have shown the presence of more dust and allergens in
      carpets compared with non-carpeted floors. At the same time, adverse effects of
      carpeted floors on perceived indoor air quality as well as worsening of symptoms
      in individuals with asthma and allergies were reported. Avoiding extensive carpet
      use in offices, schools, kindergartens and bedrooms has therefore been
      recommended by several health authorities. More recently, carpet producers have
      argued that former assessments were obsolete and that modern rugs are
      unproblematic, even for those with asthma and allergies. To investigate whether
      the recommendation to be cautious with the use of carpets is still valid, or
      whether there are new data supporting that carpet flooring do not present a
      problem for indoor air quality and health, we have reviewed the literature on
      this matter. We have not found updated peer reviewed evidence that carpeted floor
      is unproblematic for the indoor environment. On the contrary, also more recent
      data support that carpets may act as a repository for pollutants which may become
      resuspended upon activity in the carpeted area. Also, the use of carpets is still
      linked to perception of reduced indoor air quality as well as adverse health
      effects as previously reported. To our knowledge, there are no publications that
      report on deposition of pollutants and adverse health outcomes associated with
      modern rugs. However, due to the three-dimensional structure of carpets, any
      carpet will to some extent act like a sink. Thus, continued caution should still
      be exercised when considering the use of wall-to-wall carpeted floors in schools,
      kindergartens and offices, as well as in children's bedrooms unless special needs
      indicate that carpets are preferable.

PMID- 29360765
TI  - Economic Conditions May Contribute to Increased Violence toward Children: A
      Nationwide Population-Based Analysis of Pediatric Injuries in Taiwanese Emergency
      Departments.
AB  - Childhood injuries are unfortunately common. Analysis procedures may assist
      professionals who work with children with developing preventive measures for
      protecting children's wellness. This study explores the causes of pediatric
      injuries presenting to an emergency department in Taiwan. This nationwide,
      population-based study was conducted using data from the National Health
      Insurance Research Database of Taiwan (NHIRD). Patients aged <18 years were
      identified from approximately one million individuals listed in the NHIRD. We
      followed up with these patients for nine years and analyzed the causes of
      injuries requiring presentation to an emergency department. Variables of interest
      were age, sex, injury mechanisms, and temporal trends. A total of 274,028
      children were identified in our study. Between 2001 and 2009, the leading causes
      of pediatric injuries treated in emergency departments were motor vehicle
      injuries, falls, and homicide. The overall incidence of injuries declined over
      the course of the study because of reductions in motor vehicle accidents and
      falls. The incidence of homicide increased during the study period, particularly
      between 2007 and 2009. A moderately inverse correlation between homicide rate and
      economic growth was observed (correlation coefficient: -0.613, p = 0.041). There
      was a general decline in pediatric injuries between 2001 and 2009. Public policy
      changes, including motorcycle helmet laws and increases in alcohol taxes, may
      have contributed to this decline. Unfortunately, the incidence of homicide
      increased over the course of the study. Ongoing financial crises may have
      contributed to this increase. Multidisciplinary efforts are required to reduce
      homicide and reinforce the importance of measures that protect children against
      violence.

PMID- 29360767
TI  - Vertical Geochemical Variations and Speciation Studies of As, Fe, Mn Zn, and Cu
      in the Sediments of the Central Gangetic Basin: Sequential Extraction and
      Statistical Approach.
AB  - A geochemical and speciation study of As, Fe, Mn, Zn, and Cu was performed using
      sequential extraction and statistical approaches in the core sediments taken at
      two locations-Rigni Chhapra and Chaube Chhapra-of the central Gangetic basin
      (India). A gradual increase in the grain size (varying from clay to coarse sands)
      was observed in both the core profiles up to 30.5 m depth. The concentrations of
      analyzed elements ranged as follows: 6.9-14.2 mg/kg for As, 13,849-31,088 mg/kg
      for Fe, 267-711 mg/kg for Mn, 45-164 mg/kg for Cu for Rigni Chhapra while for
      Chaube Chhapra the range was 7.5-13.2 mg/kg for As, 10,936-37,052 mg/kg for Fe,
      267-1052 mg/kg for Mn, 60-198 mg/kg for Zn and 60-108 mg/kg for Cu. Significant
      amounts (53-95%) of all the fractionated elemental concentrations were bound
      within the crystal structure of the minerals as a residual fraction. The
      reducible fraction was the second most dominant fraction for As (7% and 8%), Fe
      (3%), Mn (20% and 26%), and Cu (7% and 6%) respectively for both the cores. It
      may be released when aquifers subjected to changing redox conditions. The acid
      soluble fraction was of most interest because it could quickly mobilize into the
      water system which formed the third most dominating among all three fractions.
      Four color code of sediments showed an association with total As concentration
      and did not show a relation with any fraction of all elements analyzed. The core
      sediment was observed enriched with As and other elements (Cu, Fe, Mn, and Zn).
      However, it fell under uncontaminated to moderately contaminate which might
      exhibit a low risk in prevailing natural conditions. X-ray diffraction analyses
      indicated the availability of siderite and magnetite minerals in the core
      sediments in a section of dark grey with micaceous medium sand with organic
      matter (black).

PMID- 29360766
TI  - Coffee Intake Decreases Risk of Postmenopausal Breast Cancer: A Dose-Response
      Meta-Analysis on Prospective Cohort Studies.
AB  - Aim: A dose-response meta-analysis was conducted in order to summarize the
      evidence from prospective cohort studies regarding the association between coffee
      intake and breast cancer risk. Methods: A systematic search was performed in
      electronic databases up to March 2017 to identify relevant studies; risk
      estimates were retrieved from the studies and linear and non-linear dose-response
      analysis modelled by restricted cubic splines was conducted. A stratified and
      subgroup analysis by menopausal and estrogen/progesterone receptor (ER/PR)
      status, smoking status and body mass index (BMI) were performed in order to
      detect potential confounders. Results: A total of 21 prospective studies were
      selected either for dose-response, the highest versus lowest category of
      consumption or subgroup analysis. The dose-response analysis of 13 prospective
      studies showed no significant association between coffee consumption and breast
      cancer risk in the non-linear model. However, an inverse relationship has been
      found when the analysis was restricted to post-menopausal women. Consumption of
      four cups of coffee per day was associated with a 10% reduction in postmenopausal
      cancer risk (relative risk, RR 0.90; 95% confidence interval, CI 0.82 to 0.99).
      Subgroup analyses showed consistent results for all potential confounding factors
      examined. Conclusions: Findings from this meta-analysis may support the
      hypothesis that coffee consumption is associated with decreased risk of
      postmenopausal breast cancer.

PMID- 29360768
TI  - Pharmacokinetic Study of Bioactive Flavonoids in the Traditional Japanese
      Medicine Keigairengyoto Exerting Antibacterial Effects against Staphylococcus
      aureus.
AB  - Recent studies have demonstrated that flavonoid glucuronides can be deconjugated
      to the active form aglycone by beta-glucuronidase-expressing macrophages.
      Keigairengyoto (KRT) is a flavonoid-rich traditional Japanese medicine reported
      to enhance bacterial clearance through immune modulation. Our aims are to examine
      the pharmacokinetics of KRT flavonoids and to identify active flavonoids
      contributing to the adjuvant effects of KRT. KRT was evaluated at pharmacokinetic
      analysis to quantify absorbed flavonoids, and cutaneous infection assay induced
      in mice by inoculation of Staphylococcus aureus. Preventive or therapeutic KRT
      administration reduced the number of bacteria in the infection site as well as
      macroscopic and microscopic lesion scores with efficacies similar to antibiotics.
      Pharmacokinetic study revealed low plasma levels of flavonoid aglycones after KRT
      administration; however, plasma concentrations were enhanced markedly by beta
      glucuronidase treatment, with baicalein the most abundant (Cmax, 1.32 ug/mL). In
      random screening assays, flavonoids such as bacalein, genistein, and apigenin
      enhanced bacteria phagocytosis by macrophages. Glucuronide bacalin was converted
      to aglycone baicalein by incubation with living macrophages, macrophage lysate,
      or skin homogenate. Taken together, the adjuvant effect of KRT may be due to some
      blood-absorbed flavonoids which enhance macrophage functions in host defense.
      Flavonoid-rich KRT may be a beneficial treatment for infectious skin
      inflammation.

PMID- 29360770
TI  - Hydroxytyrosol: Health Benefits and Use as Functional Ingredient in Meat.
AB  - Hydroxytyrosol (HXT) is a phenolic compound drawn from the olive tree and its
      leaves as a by-product obtained from the manufacturing of olive oil. It is
      considered the most powerful antioxidant compound after gallic acid and one of
      the most powerful antioxidant compounds between phenolic compounds from olive
      tree followed by oleuropein, caffeic and tyrosol. Due to its molecular structure,
      its regular consumption has several beneficial effects such as antioxidant, anti
      inflammatory, anticancer, and as a protector of skin and eyes, etc. For these
      reasons, the use of HXT extract is a good strategy for use in meat products to
      replace synthetics additives. However, this extract has a strong odour and
      flavour, so it is necessary to previously treat this compound in order to not
      alter the organoleptic quality of the meat product when is added as ingredient.
      The present review exposes the health benefits provided by HXT consumption and
      the latest research about its use on meat. In addition, new trends about the
      application of HXT in the list of ingredients of healthier meat products will be
      discussed.

PMID- 29360771
TI  - Biotherapeutic Effect of Gingival Stem Cells Conditioned Medium in Bone Tissue
      Restoration.
AB  - Bone tissue engineering is one of the main branches of regenerative medicine. In
      this field, the use of a scaffold, which supported bone development, in
      combination with mesenchymal stem cells (MSCs), has promised better outcomes for
      bone regeneration. In particular, human gingival mesenchymal stem cells (hGMSCs)
      may present advantages compared to other MSCs, including the easier isolation.
      However, MSCs' secretome has attracted much attention for its potential use in
      tissue regeneration, such as conditioned medium (CM) that contains different
      soluble factors proved to be useful for the regenerative purposes. In this study,
      we evaluated the osteogenic capacity of a poly-(lactide) (3D-PLA) scaffold
      enriched with hGMSCs and hGMSCs derived CM and its ability to regenerate bone
      defects in rat calvarias. 3D-PLA alone, 3D-PLA + CM or 3D-PLA + hGMSCs
      with/without CM were implanted in Wistar male rats subjected to calvarial
      defects. We observed that 3D-PLA scaffold enriched with hGMSCs and CM showed a
      better osteogenic capacity, being able to repair the calvarial defect as revealed
      in vivo by morphological evaluation. Moreover, transcriptomic analysis in vitro
      revealed the upregulation of genes involved in ossification and regulation of
      ossification in the 3D-PLA + CM + hGMSCs group. All of these results indicate the
      great osteogenic ability of 3D-PLA + CM + hGMSCs supporting its use in bone
      regenerative medicine, in particular in the repair of cranial bone defects.
      Especially, hGMSCs derived CM played a key role in the induction of the
      osteogenic process and in bone regeneration.

PMID- 29360772
TI  - Thermoreversibly Cross-Linked EPM Rubber Nanocomposites with Carbon Nanotubes.
AB  - Conductive rubber nanocomposites were prepared by dispersing conductive nanotubes
      (CNT) in thermoreversibly cross-linked ethylene propylene rubbers grafted with
      furan groups (EPM-g-furan) rubbers. Their features were studied with a strong
      focus on conductive and mechanical properties relevant for strain-sensor
      applications. The Diels-Alder chemistry used for thermoreversible cross-linking
      allows for the preparation of fully recyclable, homogeneous, and conductive
      nanocomposites. CNT modified with compatible furan groups provided nanocomposites
      with a relatively large tensile strength and small elongation at break. High and
      low sensitivity deformation experiments of nanocomposites with 5 wt % CNT (at the
      percolation threshold) displayed an initially linear sensitivity to deformation.
      Notably, only fresh samples displayed a linear response of their electrical
      resistivity to deformations as the resistance variation collapsed already after
      one cycle of elongation. Notwithstanding this mediocre performance as a strain
      sensor, the advantages of using thermoreversible chemistry in a conductive rubber
      nanocomposite were highlighted by demonstrating crack-healing by welding due to
      the joule effect on the surface and the bulk of the material. This will open up
      new technological opportunities for the design of novel strain-sensors based on
      recyclable rubbers.

PMID- 29360774
TI  - Kinetics of Ion-Capturing/Ion-Releasing Processes in Liquid Crystal Devices
      Utilizing Contaminated Nanoparticles and Alignment Films.
AB  - Various types of nanomaterials and alignment layers are considered major
      components of the next generation of advanced liquid crystal devices. While the
      steady-state properties of ion-capturing/ion-releasing processes in liquid
      crystals doped with nanoparticles and sandwiched between alignment films are
      relatively well understood, the kinetics of these phenomena remains practically
      unexplored. In this paper, the time dependence of ion-capturing/ion-releasing
      processes in liquid crystal cells utilizing contaminated nanoparticles and
      alignment layers is analyzed. The ionic contamination of both nanodopants and
      alignment films governs the switching between ion-capturing and ion-releasing
      regimes. The time dependence (both monotonous and non-monotonous) of these
      processes is characterized by time constants originated from the presence of
      nanoparticles and films, respectively. These time constants depend on the ion
      adsorption/ion desorption parameters and can be tuned by changing the
      concentration of nanoparticles, their size, and the cell thickness.

PMID- 29360773
TI  - Identification of Proteins Involved in Carbohydrate Metabolism and Energy
      Metabolism Pathways and Their Regulation of Cytoplasmic Male Sterility in Wheat.
AB  - Cytoplasmic male sterility (CMS) where no functional pollen is produced has
      important roles in wheat breeding. The anther is a unique organ for male
      gametogenesis and its abnormal development can cause male sterility. However, the
      mechanisms and regulatory networks related to plant male sterility are poorly
      understood. In this study, we conducted comparative analyses using isobaric tags
      for relative and absolute quantification (iTRAQ) of the pollen proteins in a CMS
      line and its wheat maintainer. Differentially abundant proteins (DAPs) were
      analyzed based on Gene Ontology classifications, metabolic pathways and
      transcriptional regulation networks using Blast2GO. We identified 5570 proteins
      based on 23,277 peptides, which matched with 73,688 spectra, including proteins
      in key pathways such as glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase
      and 6-phosphofructokinase 1 in the glycolysis pathway, isocitrate dehydrogenase
      and citrate synthase in the tricarboxylic acid cycle and nicotinamide adenine
      dinucleotide (NADH)-dehydrogenase and adenosine-triphosphate (ATP) synthases in
      the oxidative phosphorylation pathway. These proteins may comprise a network that
      regulates male sterility in wheat. Quantitative real time polymerase chain
      reaction (qRT-PCR) analysis, ATP assays and total sugar assays validated the
      iTRAQ results. These DAPs could be associated with abnormal pollen grain
      formation and male sterility. Our findings provide insights into the molecular
      mechanism related to male sterility in wheat.

PMID- 29360775
TI  - Faecal Pathogen Flows and Their Public Health Risks in Urban Environments: A
      Proposed Approach to Inform Sanitation Planning.
AB  - Public health benefits are often a key political driver of urban sanitation
      investment in developing countries, however, pathogen flows are rarely taken
      systematically into account in sanitation investment choices. While several tools
      and approaches on sanitation and health risks have recently been developed, this
      research identified gaps in their ability to predict faecal pathogen flows, to
      relate exposure risks to the existing sanitation services, and to compare
      expected impacts of improvements. This paper outlines a conceptual approach that
      links faecal waste discharge patterns with potential pathogen exposure pathways
      to quantitatively compare urban sanitation improvement options. An illustrative
      application of the approach is presented, using a spreadsheet-based model to
      compare the relative effect on disability-adjusted life years of six sanitation
      improvement options for a hypothetical urban situation. The approach includes
      consideration of the persistence or removal of different pathogen classes in
      different environments; recognition of multiple interconnected sludge and
      effluent pathways, and of multiple potential sites for exposure; and use of
      quantitative microbial risk assessment to support prediction of relative health
      risks for each option. This research provides a step forward in applying current
      knowledge to better consider public health, alongside environmental and other
      objectives, in urban sanitation decision making. Further empirical research in
      specific locations is now required to refine the approach and address data gaps.

PMID- 29360776
TI  - Involvement of Bradykinin B2 Receptor in Pathological Vascularization in Oxygen
      Induced Retinopathy in Mice and Rabbit Cornea.
AB  - The identification of components of the kallikrein-kinin system in the vitreous
      from patients with microvascular retinal diseases suggests that bradykinin (BK)
      signaling may contribute to pathogenesis of retinal vascular complications. BK
      receptor 2 (B2R) signaling has been implicated in both pro-inflammatory and pro
      angiogenic effects promoted by BK. Here, we investigated the role of BK/B2R
      signaling in the retinal neovascularization in the oxygen-induced retinopathy
      (OIR) model. Blockade of B2R signaling by the antagonist fasitibant delayed
      retinal vascularization in mouse pups, indicating that the retinal endothelium is
      a target of the BK/B2R system. In the rabbit cornea assay, a model of
      pathological neoangiogenesis, the B2 agonist kallidin induced vessel sprouting
      and promoted cornea opacity, a sign of edema and tissue inflammation. In
      agreement with these results, in the OIR model, a blockade of B2R signaling
      significantly reduced retinal neovascularization, as determined by the area of
      retinal tufts, and, in the retinal vessel, it also reduced vascular endothelial
      growth factor and fibroblast growth factor-2 expression. All together, these
      findings show that B2R blockade reduces retinal neovascularization and inhibits
      the expression of proangiogenic and pro-inflammatory cytokines, suggesting that
      targeting B2R signaling may be an effective strategy for treating ischemic
      retinopathy.

PMID- 29360777
TI  - Review of Supported Pd-Based Membranes Preparation by Electroless Plating for
      Ultra-Pure Hydrogen Production.
AB  - In the last years, hydrogen has been considered as a promising energy vector for
      the oncoming modification of the current energy sector, mainly based on fossil
      fuels. Hydrogen can be produced from water with no significant pollutant
      emissions but in the nearest future its production from different hydrocarbon raw
      materials by thermochemical processes seems to be more feasible. In any case, a
      mixture of gaseous compounds containing hydrogen is produced, so a further
      purification step is needed to purify the hydrogen up to required levels
      accordingly to the final application, i.e., PEM fuel cells. In this mean,
      membrane technology is one of the available separation options, providing an
      efficient solution at reasonable cost. Particularly, dense palladium-based
      membranes have been proposed as an ideal chance in hydrogen purification due to
      the nearly complete hydrogen selectivity (ideally 100%), high thermal stability
      and mechanical resistance. Moreover, these membranes can be used in a membrane
      reactor, offering the possibility to combine both the chemical reaction for
      hydrogen production and the purification step in a unique device. There are many
      papers in the literature regarding the preparation of Pd-based membranes, trying
      to improve the properties of these materials in terms of permeability, thermal
      and mechanical resistance, poisoning and cost-efficiency. In this review, the
      most relevant advances in the preparation of supported Pd-based membranes for
      hydrogen production in recent years are presented. The work is mainly focused in
      the incorporation of the hydrogen selective layer (palladium or palladium-based
      alloy) by the electroless plating, since it is one of the most promising
      alternatives for a real industrial application of these membranes. The
      information is organized in different sections including: (i) a general
      introduction; (ii) raw commercial and modified membrane supports; (iii) metal
      deposition insights by electroless-plating; (iv) trends in preparation of Pd
      based alloys, and, finally; (v) some essential concluding remarks in addition to
      futures perspectives.

PMID- 29360778
TI  - Effects of Substitution, and Adding of Carbohydrate and Fat to Whey-Protein on
      Energy Intake, Appetite, Gastric Emptying, Glucose, Insulin, Ghrelin, CCK and GLP
      1 in Healthy Older Men-A Randomized Controlled Trial.
AB  - Protein-rich supplements are used widely for the management of malnutrition in
      the elderly. We reported previously that the suppression of energy intake by whey
      protein is less in older than younger adults. The aim was to determine the
      effects of substitution, and adding of carbohydrate and fat to whey protein, on
      ad libitum energy intake from a buffet meal (180-210 min), gastric emptying (3D
      ultrasonography), plasma gut hormone concentrations (0-180 min) and appetite
      (visual analogue scales), in healthy older men. In a randomized, double-blind
      order, 13 older men (75 +/- 2 years) ingested drinks (~450 mL) containing: (i) 70
      g whey protein (280 kcal; 'P280'); (ii) 14 g protein, 28 g carbohydrate, 12.4 g
      fat (280 kcal; 'M280'); (iii) 70 g protein, 28 g carbohydrate, 12.4 g fat (504
      kcal; 'M504'); or (iv) control (~2 kcal). The caloric drinks, compared to a
      control, did not suppress appetite or energy intake; there was an increase in
      total energy intake (drink + meal, p < 0.05), which was increased most by the
      M504-drink. P280- and M504-drink ingestion were associated with slower a gastric
      emptying time (n = 9), lower ghrelin, and higher cholecystokinin (CCK) and
      glucagon-like peptide-1 (GLP-1) than M280 (p < 0.05). Glucose and insulin were
      increased most by the mixed-macronutrient drinks (p < 0.05). In conclusion,
      energy intake was not suppressed, compared to a control, and particularly whey
      protein, affected gastric emptying and gut hormone responses.

PMID- 29360779
TI  - Analytical Approaches to Improve Accuracy in Solving the Protein Topology
      Problem.
AB  - To take advantage of recent advances in genomics and proteomics it is critical
      that the three-dimensional physical structure of biological macromolecules be
      determined. Cryo-Electron Microscopy (cryo-EM) is a promising and improving
      method for obtaining this data, however resolution is often not sufficient to
      directly determine the atomic scale structure. Despite this, information for
      secondary structure locations is detectable. De novo modeling is a computational
      approach to modeling these macromolecular structures based on cryo-EM derived
      data. During de novo modeling a mapping between detected secondary structures and
      the underlying amino acid sequence must be identified. DP-TOSS (Dynamic
      Programming for determining the Topology Of Secondary Structures) is one tool
      that attempts to automate the creation of this mapping. By treating the
      correspondence between the detected structures and the structures predicted from
      sequence data as a constraint graph problem DP-TOSS achieved good accuracy in its
      original iteration. In this paper, we propose modifications to the scoring
      methodology of DP-TOSS to improve its accuracy. Three scoring schemes were
      applied to DP-TOSS and tested: (i) a skeleton-based scoring function; (ii) a
      geometry-based analytical function; and (iii) a multi-well potential energy-based
      function. A test of 25 proteins shows that a combination of these schemes can
      improve the performance of DP-TOSS to solve the topology determination problem
      for macromolecule proteins.

PMID- 29360780
TI  - Effects of Zearalenone Exposure on the TGF-beta1/Smad3 Signaling Pathway and the
      Expression of Proliferation or Apoptosis Related Genes of Post-Weaning Gilts.
AB  - Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium species, which is
      widely distributed and posed a great health risk to both humans and farm animals.
      Reproductive disorders associated with ZEA such as premature puberty, infertility
      and abortion have plagued the animal husbandry, but the molecular mechanism is
      unclear. Because transforming growth factor-beta1 (TGF-beta1) signaling pathway
      is involved in the proliferation and apoptosis of cells, proliferating cell
      nuclear antigen (PCNA), B-cell lymphoma/leukemia-2 (BCL-2) and BCL-2 associated X
      protein (BAX) that all play indispensable roles in the normal development of the
      uterus, it is hypothesized that ZEA induces reproductive disorders is closely
      related to the expression of these genes. The objective of this study was to
      assess the effects of dietary ZEA at the concentrations of 0.5 to 1.5 mg/kg on
      the mRNA and protein expression of these genes in the uteri of post-weaning gilts
      and to explore the possible molecular mechanism. Forty healthy post-weaning
      female piglets (Duroc * Landrace * Large White) aged 38 d were randomly allocated
      to basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5
      (ZEA1.5) mg/kg purified ZEA, and fed for 35 d. Piglets were euthanized at the end
      of the experiment and samples were taken and subjected to immunohistochemistry,
      qRT-PCR and Western blot analyses. The relative mRNA expressions of PCNA, BCL-2
      and Smad3 in the uteri of post-weaning gilts increased linearly (p < 0.05) and
      quadratically (p < 0.05) as ZEA concentration increased in the diet. The relative
      protein expressions of PCNA, BAX, BCL-2, TGF-beta1, Smad3, and phosphorylated
      Smad3 (p-Smad3) in the uteri of post-weaning gilts increased linearly (p < 0.05)
      and quadratically (p < 0.001) with an increasing level of ZEA. The results showed
      that uterine cells in the ZEA (0.5-1.5 mg/kg) treatments were in a high
      proliferation state, indicating that ZEA could accelerate the proliferation of
      uteri and promote the development of the uteri. At the same time, the results
      suggested that ZEA activates the TGF-beta1/Smad3 signaling pathway, suggesting it
      plays an important role in accelerating the development of the uterus.

PMID- 29360781
TI  - Assessment of Urinary Deoxynivalenol Biomarkers in UK Children and Adolescents.
AB  - Deoxynivalenol (DON), the mycotoxin produced mainly by Fusarium graminearum and
      found in contaminated cereal-based foodstuff, has been consistently detected in
      body fluids in adults. Available data in children and adolescents are scarce.
      This study assessed urinary DON concentrations in children aged 3-9 years (n =
      40) and adolescents aged 10-17 years (n = 39) in the UK. Morning urine samples
      were collected over two consecutive days and analysed for free DON (un
      metabolised form), DON-glucuronides (DON-GlcA), deepoxy deoxynivalenol (DOM-1),
      and total DON (sum of free DON, DON-GlcA, and DOM-1). Total DON was detected in
      the urine of >95% of children and adolescents on both days. Mean total DON
      concentrations (ng/mg creatinine) were 41.6 and 21.0 for children and
      adolescents, respectively. The greatest total DON levels were obtained in female
      children on both days (214 and 219 ng/mg creatinine on days 1 and 2,
      respectively). Free DON and DON-GlcA were detected in most urine specimens,
      whereas DOM-1 was not present in any sample. Estimation of dietary DON exposure
      suggested that 33-63% of children and 5-46% of adolescents exceeded current
      guidance regarding the maximum provisional tolerable daily intake (PMTDI) for
      DON. Although moderate mean urinary DON concentrations were shown, the high
      detection frequency of urinary DON, the maximum biomarker concentrations, and
      estimated dietary DON exposure are concerning.

PMID- 29360782
TI  - Antimycobacterial Activity: A New Pharmacological Target for Conotoxins Found in
      the First Reported Conotoxin from Conasprella ximenes.
AB  - Mycobacterium tuberculosis is the etiological agent of tuberculosis, an airborne
      infectious disease that is a leading cause of human morbidity and mortality
      worldwide. We report here the first conotoxin that is able to inhibit the growth
      of M. tuberculosis at a concentration similar to that of two other drugs that are
      currently used in clinics. Furthermore, it is also the first conopeptide that has
      been isolated from the venom of Conasprella ximenes. The venom gland
      transcriptome of C. ximenes was sequenced to construct a database with 24,284 non
      redundant transcripts. The conopeptide was purified from the venom using reverse
      phase high performance liquid chromatography (RP-HPLC) and was analyzed using
      electrospray ionization-mass spectrometry (ESI-MS/MS). No automatic
      identification above the identity threshold with 1% of the false discovery rate
      was obtained; however, a 10-amino-acid sequence tag, manually extracted from the
      MS/MS spectra, allowed for the identification of a conotoxin in the transcriptome
      database. Electron transfer higher energy collision dissociation (EThcD)
      fragmentation of the native conotoxin confirmed the N-terminal sequence (1-14),
      while LC-MS/MS analysis of the tryptic digest of the reduced and S-alkylated
      conotoxin confirmed the C-terminal region (15-36). The expected and experimental
      molecular masses corresponded, within sub-ppm mass error. The 37-mer peptide (MW
      4109.69 Da), containing eight cysteine residues, was named I1_xm11a, according to
      the current nomenclature for this type of molecule.

PMID- 29360785
TI  - Exploring Facilitators and Barriers to Initiation and Completion of the Human
      Papillomavirus (HPV) Vaccine Series among Parents of Girls in a Safety Net
      System.
AB  - : Objective: To assess, among parents of predominantly minority, low-income
      adolescent girls who had either not initiated (NI) or not completed (NC) the HPV
      vaccine series, attitudes and other factors important in promoting the series,
      and whether attitudes differed by language preference. Design/Methods: From
      August 2013-October 2013, we conducted a mail survey among parents of girls aged
      12-15 years randomly selected from administrative data in a Denver safety net
      system; 400 parents from each group (NI and NC) were targeted. Surveys were in
      English or Spanish. RESULTS: The response rate was 37% (244/660; 140 moved or
      gone elsewhere; 66% English-speaking, 34% Spanish-speaking). Safety attitudes of
      NIs and NCs differed, with 40% NIs vs. 14% NC's reporting they thought HPV
      vaccine was unsafe (p < 0.0001) and 43% NIs vs. 21% NCs that it may cause long
      term health problems (p < 0.001). Among NCs, 42% reported they did not know their
      daughter needed more shots (English-speaking, 20%, Spanish-speaking 52%) and 39%
      reported that "I wasn't worried about the safety of the HPV vaccine before, but
      now I am" (English-speaking, 23%, Spanish-speaking, 50%). Items rated as very
      important among NIs in the decision regarding vaccination included: more
      information about safety (74%), more information saying it prevents cancer (70%),
      and if they knew HPV was spread mainly by sexual contact (61%). Conclusions:
      Safety concerns, being unaware of the need for multiple doses, and low perceived
      risk of infection remain significant barriers to HPV vaccination for at-risk
      adolescents. Some parents' safety concerns do not appear until initial
      vaccination.

PMID- 29360787
TI  - On the Ageing of High Energy Lithium-Ion Batteries-Comprehensive Electrochemical
      Diffusivity Studies of Harvested Nickel Manganese Cobalt Electrodes.
AB  - This paper examines the impact of the characterisation technique considered for
      the determination of the L i + solid state diffusion coefficient in uncycled as
      in cycled Nickel Manganese Cobalt oxide (NMC) electrodes. As major
      characterisation techniques, Cyclic Voltammetry (CV), Galvanostatic Intermittent
      Titration Technique (GITT) and Electrochemical Impedance Spectroscopy (EIS) were
      systematically investigated. L i + diffusion coefficients during the lithiation
      process of the uncycled and cycled electrodes determined by CV at 3.71 V are
      shown to be equal to 3 . 48 * 10 - 10 cm 2 .s - 1 and 1 . 56 * 10 - 10 cm 2 .s -
      1 , respectively. The dependency of the L i + diffusion with the lithium content
      in the electrodes is further studied in this paper with GITT and EIS. Diffusion
      coefficients calculated by GITT and EIS characterisations are shown to be in the
      range between 1 . 76 * 10 - 15 cm 2 .s - 1 and 4 . 06 * 10 - 12 cm 2 .s - 1 ,
      while demonstrating the same decreasing trend with the lithiation process of the
      electrodes. For both electrode types, diffusion coefficients calculated by CV
      show greater values compared to those determined by GITT and EIS. With ageing, CV
      and EIS techniques lead to diffusion coefficients in the electrodes at 3.71 V
      that are decreasing, in contrast to GITT for which results indicate increasing
      diffusion coefficient. After long-term cycling, ratios of the diffusion
      coefficients determined by GITT compared to CV become more significant with an
      increase about 1 order of magnitude, while no significant variation is seen
      between the diffusion coefficients calculated from EIS in comparison to CV.

PMID- 29360786
TI  - Study on Urban Heat Island Intensity Level Identification Based on an Improved
      Restricted Boltzmann Machine.
AB  - Thermal infrared remote sensing has become one of the main technology methods
      used for urban heat island research. When applying urban land surface temperature
      inversion of the thermal infrared band, problems with intensity level division
      arise because the method is subjective. However, this method is one of the few
      that performs heat island intensity level identification. This paper will build
      an intensity level identifier for an urban heat island, by using weak supervision
      and thought-based learning in an improved, restricted Boltzmann machine (RBM)
      model. The identifier automatically initializes the annotation and optimizes the
      model parameters sequentially until the target identifier is completed. The
      algorithm needs very little information about the weak labeling of the target
      training sample and generates an urban heat island intensity spatial distribution
      map. This study can provide reliable decision-making support for urban ecological
      planning and effective protection of urban ecological security. The experimental
      results showed the following: (1) The heat island effect in Wuhan is existent and
      intense. Heat island areas are widely distributed. The largest heat island area
      is in Wuhan, followed by the sub-green island. The total area encompassed by heat
      island and strong island levels accounts for 54.16% of the land in Wuhan. (2)
      Partially based on improved RBM identification, this method meets the research
      demands of determining the spatial distribution characteristics of the internal
      heat island effect; its identification accuracy is superior to that of comparable
      methods.

PMID- 29360783
TI  - Toxicodynamics of Mycotoxins in the Framework of Food Risk Assessment-An In
      Silico Perspective.
AB  - Mycotoxins severely threaten the health of humans and animals. For this reason,
      many countries have enforced regulations and recommendations to reduce the
      dietary exposure. However, even though regulatory actions must be based on solid
      scientific knowledge, many aspects of their toxicological activity are still
      poorly understood. In particular, deepening knowledge on the primal molecular
      events triggering the toxic stimulus may be relevant to better understand the
      mechanisms of action of mycotoxins. The present work presents the use of in
      silico approaches in studying the mycotoxins toxicodynamics, and discusses how
      they may contribute in widening the background of knowledge. A particular
      emphasis has been posed on the methods accounting the molecular initiating events
      of toxic action. In more details, the key concepts and challenges of mycotoxins
      toxicology have been introduced. Then, topical case studies have been presented
      and some possible practical implementations of studying mycotoxins toxicodynamics
      have been discussed.

PMID- 29360788
TI  - Solvation and Aggregation of Meta-Aminobenzoic Acid in Water: Density Functional
      Theory and Molecular Dynamics Study.
AB  - Meta-aminobenzoic acid, an important model system in the study of polymorphism
      and crystallization of active pharmaceutical ingredients, exist in water in both
      the nonionic (mABA) and zwitterionic (mABA+/-) forms. However, the constituent
      molecules of the polymorph that crystallizes from aqueous solutions are
      zwitterionic. This study reports atomistic simulations of the events surrounding
      the early stage of crystal nucleation of meta-aminobenzoic acid from aqueous
      solutions. Ab initio molecular dynamics was used to simulate the hydration of
      mABA+/- and mABA and to quantify the interaction of these molecules with the
      surrounding water molecules. Density functional theory calculations were
      conducted to determine the low-lying energy conformers of meta-aminobenzoic acid
      dimers and to compute the Gibbs free energies in water of nonionic, (mABA)2,
      zwitterionic, (mABA+/-)2, and nonionic-zwitterionic, (mABA)(mABA+/-), species.
      Classical molecular dynamics simulations of mixed mABA-mABA+/- aqueous solutions
      were carried out to examine the aggregation of meta-aminobenzoic acid. According
      to these simulations, the selective crystallization of the polymorphs whose
      constituent molecules are zwitterionic is driven by the formation of zwitterionic
      dimers in solution, which are thermodynamically more stable than (mABA)2 and
      (mABA)(mABA+/-) pairs. This work represents a paradigm of the role of molecular
      processes during the early stages of crystal nucleation in affecting polymorph
      selection during crystallization from solution.

PMID- 29360789
TI  - Durable Self-Cleaning Coatings for Architectural Surfaces by Incorporation of
      TiO2 Nano-Particles into Hydroxyapatite Films.
AB  - To prevent soiling of marble exposed outdoors, the use of TiO2 nano-particles has
      been proposed in the literature by two main routes, both raising durability
      issues: (i) direct application to marble surface, with the risk of particle
      leaching by rainfall; (ii) particle incorporation into inorganic or organic
      coatings, with the risk of organic coating degradation catalyzed by TiO2
      photoactivity. Here, we investigated the combination of nano-TiO2 and
      hydroxyapatite (HAP), previously developed for marble protection against
      dissolution in rain and mechanical consolidation. HAP-TiO2 combination was
      investigated by two routes: (i) sequential application of HAP followed by nano
      TiO2 ("H+T"); (ii) simultaneous application by introducing nano-TiO2 into the
      phosphate solution used to form HAP ("HT"). The self-cleaning ability was
      evaluated before and after prolonged exposure to simulated rain. "H+T" and "HT"
      coatings exhibited much better resistance to nano-TiO2 leaching by rain, compared
      to TiO2 alone. In "H+T" samples, TiO2 nano-particles adhere better to HAP (having
      flower-like morphology and high specific surface area) than to marble. In "HT"
      samples, thanks to chemical bonds between nano-TiO2 and HAP, the particles are
      firmly incorporated in the HAP coating, which protects them from leaching by
      rain, without diminishing their photoactivity and without being degraded by them.

PMID- 29360790
TI  - A Compact and Low Power RO PUF with High Resilience to the EM Side-Channel Attack
      and the SVM Modelling Attack of Wireless Sensor Networks.
AB  - Authentication is a crucial security service for the wireless sensor networks
      (WSNs) in versatile domains. The deployment of WSN devices in the untrusted open
      environment and the resource-constrained nature make the on-chip authentication
      an open challenge. The strong physical unclonable function (PUF) came in handy as
      light-weight authentication security primitive. In this paper, we present the
      first ring oscillator (RO) based strong physical unclonable function (PUF) with
      high resilience to both the electromagnetic (EM) side-channel attack and the
      support vector machine (SVM) modelling attack. By employing an RO based PUF
      architecture with the current starved inverter as the delay cell, the oscillation
      power is significantly reduced to minimize the emitted EM signal, leading to
      greatly enhanced immunity to the EM side-channel analysis attack. In addition,
      featuring superior reconfigurability due to the conspicuously simplified
      circuitries, the proposed implementation is capable of withstanding the SVM
      modelling attack by generating and comparing a large number of RO frequency
      pairs. The reported experimental results validate the prototype of a 9-stage RO
      PUF fabricated using standard 65 nm complementary-metal-oxide-semiconductor
      (CMOS) process. Operating at the supply voltage of 1.2 V and the frequency of 100
      KHz, the fabricated RO PUF occupies a compact silicon area of 250 MU m 2 and
      consumes a power as low as 5.16 MU W per challenge-response pair (CRP).
      Furthermore, the uniqueness and the worst-case reliability are measured to be
      50.17% and 98.30% for the working temperature range of -40~120 ? C and the supply
      voltage variation of +/-2%, respectively. Thus, the proposed PUF is applicable
      for the low power, low cost and secure WSN communications.

PMID- 29360791
TI  - Simultaneous Event-Triggered Fault Detection and Estimation for Stochastic
      Systems Subject to Deception Attacks.
AB  - In this paper, a synthesized design of fault-detection filter and fault estimator
      is considered for a class of discrete-time stochastic systems in the framework of
      event-triggered transmission scheme subject to unknown disturbances and deception
      attacks. A random variable obeying the Bernoulli distribution is employed to
      characterize the phenomena of the randomly occurring deception attacks. To
      achieve a fault-detection residual is only sensitive to faults while robust to
      disturbances, a coordinate transformation approach is exploited. This approach
      can transform the considered system into two subsystems and the unknown
      disturbances are removed from one of the subsystems. The gain of fault-detection
      filter is derived by minimizing an upper bound of filter error covariance.
      Meanwhile, system faults can be reconstructed by the remote fault estimator. An
      recursive approach is developed to obtain fault estimator gains as well as
      guarantee the fault estimator performance. Furthermore, the corresponding event
      triggered sensor data transmission scheme is also presented for improving working
      life of the wireless sensor node when measurement information are aperiodically
      transmitted. Finally, a scaled version of an industrial system consisting of
      local PC, remote estimator and wireless sensor node is used to experimentally
      evaluate the proposed theoretical results. In particular, a novel fault-alarming
      strategy is proposed so that the real-time capacity of fault-detection is
      guaranteed when the event condition is triggered.

PMID- 29360792
TI  - Data-Driven Packet Loss Estimation for Node Healthy Sensing in Decentralized
      Cluster.
AB  - Decentralized clustering of modern information technology is widely adopted in
      various fields these years. One of the main reason is the features of high
      availability and the failure-tolerance which can prevent the entire system form
      broking down by a failure of a single point. Recently, toolkits such as Akka are
      used by the public commonly to easily build such kind of cluster. However,
      clusters of such kind that use Gossip as their membership managing protocol and
      use link failure detecting mechanism to detect link failures cannot deal with the
      scenario that a node stochastically drops packets and corrupts the member status
      of the cluster. In this paper, we formulate the problem to be evaluating the link
      quality and finding a max clique (NP-Complete) in the connectivity graph. We then
      proposed an algorithm that consists of two models driven by data from application
      layer to respectively solving these two problems. Through simulations with
      statistical data and a real-world product, we demonstrate that our algorithm has
      a good performance.

PMID- 29360793
TI  - Spatial Vertical Directionality and Correlation of Low-Frequency Ambient Noise in
      Deep Ocean Direct-Arrival Zones.
AB  - Wind-driven and distant shipping noise sources contribute to the total noise
      field in the deep ocean direct-arrival zones. Wind-driven and distant shipping
      noise sources may significantly and simultaneously affect the spatial
      characteristics of the total noise field to some extent. In this work, a ray
      approach and parabolic equation solution method were jointly utilized to model
      the low-frequency ambient noise field in a range-dependent deep ocean environment
      by considering their calculation accuracy and efficiency in near-field wind
      driven and far-field distant shipping noise fields. The reanalysis databases of
      National Center of Environment Prediction (NCEP) and Volunteer Observation System
      (VOS) were used to model the ambient noise source intensity and distribution.
      Spatial vertical directionality and correlation were analyzed in three scenarios
      that correspond to three wind speed conditions. The noise field was dominated by
      distant shipping noise sources when the wind speed was less than 3 m/s, and then
      the spatial vertical directionality and vertical correlation of the total noise
      field were nearly consistent with those of distant shipping noise field. The
      total noise field was completely dominated by near field wind generated noise
      sources when the wind speed was greater than 12 m/s at 150 Hz, and then the
      spatial vertical correlation coefficient and directionality pattern of the total
      noise field was approximately consistent with that of the wind-driven noise
      field. The spatial characteristics of the total noise field for wind speeds
      between 3 m/s and 12 m/s were the weighted results of wind-driven and distant
      shipping noise fields. Furthermore, the spatial characteristics of low-frequency
      ambient noise field were compared with the classical Cron/Sherman deep water
      noise field coherence function. Simulation results with the described modeling
      method showed good agreement with the experimental measurement results based on
      the vertical line array deployed near the bottom in deep ocean direct-arrival
      zones.

PMID- 29360795
TI  - Single-Photon Tracking for High-Speed Vision.
AB  - Quanta Imager Sensors provide photon detections at high frame rates, with
      negligible read-out noise, making them ideal for high-speed optical tracking. At
      the basic level of bit-planes or binary maps of photon detections, objects may
      present limited detail. However, through motion estimation and spatial
      reassignment of photon detections, the objects can be reconstructed with minimal
      motion artefacts. We here present the first demonstration of high-speed two
      dimensional (2D) tracking and reconstruction of rigid, planar objects with a
      Quanta Image Sensor, including a demonstration of depth-resolved tracking.

PMID- 29360794
TI  - Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of
      Precision Medicine.
AB  - Androgen deprivation therapy (ADT) has been widely prescribed for patients with
      advanced prostate cancer (PC) to control key signaling pathways via androgen
      receptor (AR) and AR-collaborative transcriptional factors; however, PC gradually
      acquires a lethal phenotype and results in castration-resistant PC (CRPC) during
      ADT. Therefore, new therapeutic strategies are required in clinical practice. In
      addition, ARs; estrogen receptors (ERs; ERalpha and ERbeta); and estrogen-related
      receptors (ERRs; ERRalpha, ERRbeta, and ERRgamma) have been reported to be
      involved in the development or regulation of PC. Recent investigations have
      revealed the role of associated molecules, such as KLF5, FOXO1, PDGFA, VEGF-A,
      WNT5A, TGFbeta1, and micro-RNA 135a of PC, via ERs and ERRs. Selective ER
      modulators (SERMs) have been developed. Recently, estrogen and androgen blockade
      (EAB) using a combination of toremifene and ADT has been demonstrated to improve
      biochemical recurrence rate in treatment-naive bone metastatic PC. In the future,
      the suitability of ADT alone or EAB for individuals may be evaluated by making
      clinical decisions on the basis of information obtained from RT-PCR, gene-panel,
      or liquid biopsy to create a "personalized medicine" or "precision medicine". In
      this review, we summarize ER and ERR signaling pathways, molecular diagnosis, and
      SERMs as candidates for advanced PC treatment.

PMID- 29360796
TI  - An Efficient Direct Position Determination Method for Multiple Strictly
      Noncircular Sources.
AB  - This paper focuses on the localization methods for multiple sources received by
      widely separated arrays. The conventional two-step methods extract measurement
      parameters and then estimate the positions from them. In the contrast to the
      conventional two-step methods, direct position determination (DPD) localizes
      transmitters directly from original sensor outputs without estimating
      intermediate parameters, resulting in higher location accuracy and avoiding the
      data association. Existing subspace data fusion (SDF)-based DPD developed in the
      frequency domain is computationally attractive in the presence of multiple
      transmitters, whereas it does not use special properties of signals. This paper
      proposes an improved SDF-based DPD algorithm for strictly noncircular sources. We
      first derive the property of strictly noncircular signals in the frequency
      domain. On this basis, the observed frequency-domain vectors at all arrays are
      concatenated and extended by exploiting the noncircular property, producing
      extended noise subspaces. Fusing the extended noise subspaces of all frequency
      components and then performing a unitary transformation, we obtain a cost
      function for each source location, which is formulated as the smallest eigenvalue
      of a real-valued matrix. To avoid the exhaustive grid search and solve this
      nonlinear function efficiently, we devise a Newton-type iterative method using
      matrix Eigen-perturbation theory. Simulation results demonstrate that the
      proposed DPD using Newton-type iteration substantially reduces the running time,
      and its performance is superior to other localization methods for both near-field
      and far-field noncircular sources.

PMID- 29360797
TI  - Present and Future of Dengue Fever in Nepal: Mapping Climatic Suitability by
      Ecological Niche Model.
AB  - Both the number of cases of dengue fever and the areas of outbreaks within Nepal
      have increased significantly in recent years. Further expansion and range shift
      is expected in the future due to global climate change and other associated
      factors. However, due to limited spatially-explicit research in Nepal, there is
      poor understanding about the present spatial distribution patterns of dengue risk
      areas and the potential range shift due to future climate change. In this
      context, it is crucial to assess and map dengue fever risk areas in Nepal. Here,
      we used reported dengue cases and a set of bioclimatic variables on the MaxEnt
      ecological niche modeling approach to model the climatic niche and map present
      and future (2050s and 2070s) climatically suitable areas under different
      representative concentration pathways (RCP2.6, RCP6.0 and RCP8.5). Simulation
      based estimates suggest that climatically suitable areas for dengue fever are
      presently distributed throughout the lowland Tarai from east to west and in river
      valleys at lower elevations. Under the different climate change scenarios, these
      areas will be slightly shifted towards higher elevation with varied magnitude and
      spatial patterns. Population exposed to climatically suitable areas of dengue
      fever in Nepal is anticipated to further increase in both 2050s and 2070s on all
      the assumed emission scenarios. These findings could be instrumental to plan and
      execute the strategic interventions for controlling dengue fever in Nepal.

PMID- 29360798
TI  - Performance Evaluation of IEEE 802.11ah Networks With High-Throughput
      Bidirectional Traffic.
AB  - So far, existing sub-GHz wireless communication technologies focused on low
      bandwidth, long-range communication with large numbers of constrained devices.
      Although these characteristics are fine for many Internet of Things (IoT)
      applications, more demanding application requirements could not be met and legacy
      Internet technologies such as Transmission Control Protocol/Internet Protocol
      (TCP/IP) could not be used. This has changed with the advent of the new IEEE
      802.11ah Wi-Fi standard, which is much more suitable for reliable bidirectional
      communication and high-throughput applications over a wide area (up to 1 km). The
      standard offers great possibilities for network performance optimization through
      a number of physical- and link-layer configurable features. However, given that
      the optimal configuration parameters depend on traffic patterns, the standard
      does not dictate how to determine them. Such a large number of configuration
      options can lead to sub-optimal or even incorrect configurations. Therefore, we
      investigated how two key mechanisms, Restricted Access Window (RAW) grouping and
      Traffic Indication Map (TIM) segmentation, influence scalability, throughput,
      latency and energy efficiency in the presence of bidirectional TCP/IP traffic. We
      considered both high-throughput video streaming traffic and large-scale reliable
      sensing traffic and investigated TCP behavior in both scenarios when the link
      layer introduces long delays. This article presents the relations between
      attainable throughput per station and attainable number of stations, as well as
      the influence of RAW, TIM and TCP parameters on both. We found that up to 20
      continuously streaming IP-cameras can be reliably connected via IEEE 802.11ah
      with a maximum average data rate of 160 kbps, whereas 10 IP-cameras can achieve
      average data rates of up to 255 kbps over 200 m. Up to 6960 stations transmitting
      every 60 s can be connected over 1 km with no lost packets. The presented results
      enable the fine tuning of RAW and TIM parameters for throughput-demanding
      reliable applications (i.e., video streaming, firmware updates) on one hand, and
      very dense low-throughput reliable networks with bidirectional traffic on the
      other hand.

PMID- 29360799
TI  - Grasping Force Control for a Robotic Hand by Slip Detection Using Developed Micro
      Laser Doppler Velocimeter.
AB  - The purpose of this paper is to show the feasibility of grasping force control by
      feeding back signals of the developed micro-laser Doppler velocimeter (MU-LDV)
      and by discriminating whether a grasped object is slipping or not. LDV is well
      known as a high response surface velocity sensor which can measure various
      surfaces-such as metal, paper, film, and so on-thus suggesting the potential
      application of LDV as a slip sensor for grasping various objects. However, the
      use of LDV as a slip sensor has not yet been reported because the size of LDVs is
      too large to be installed on a robotic fingertip. We have solved the size problem
      and enabled the performance of a feasibility test with a few-millimeter-scale LDV
      referred to as micro-LDV (MU-LDV) by modifying the design which was adopted from
      MEMS (microelectromechanical systems) fabrication process. In this paper, by
      applying our developed MU-LDV as a slip sensor, we have successfully demonstrated
      grasping force control with three target objects-aluminum block, wood block, and
      white acrylic block-considering that various objects made of these materials can
      be found in homes and factories, without grasping force feedback. We provide
      proofs that LDV is a new promising candidate slip sensor for grasping force
      control to execute target grasping.

PMID- 29360801
TI  - Development of an Indirect ELISA Based on a Recombinant Chimeric Protein for the
      Detection of Antibodies against Bovine Babesiosis.
AB  - The current method for Babesia spp. serodiagnosis based on a crude merozoite
      antigen is a complex and time-consuming procedure. An indirect enzyme-linked
      immunosorbent assay (iELISA) based on a recombinant multi-antigen of Babesia
      bovis (rMABbO) was developed for detection of antibodies in bovines suspected of
      infection with this parasite. The multi-antigen comprises gene fragments of three
      previously characterized B. bovis antigens: MSA-2c, RAP-1 and the Heat Shock
      protein 20 that are well-conserved among geographically distant strains. The
      cutoff value for the new rMABbo-iELISA was determined using 75 known-positive and
      300 known-negative bovine sera previously tested for antibodies to B. bovis by
      the gold-standard ELISA which uses a merozoite lysate. A cutoff value of >=35%
      was determined in these samples by receiver operator characteristic (ROC) curve
      analysis, showing a sensitivity of 95.9% and a specificity of 94.3%. The rMABbo
      iELISA was further tested in a blind trial using an additional set of 263 field
      bovine sera from enzootic and tick-free regions of Argentina. Results showed a
      good agreement with the gold standard test with a Cohen's kappa value of 0.76.
      Finally, the prevalence of bovine babesiosis in different tick enzootic regions
      of Argentina was analyzed where seropositivity values among 68-80% were obtained.
      A certain level of cross reaction was observed when samples from B. bigemina
      infected cattle were analyzed with the new test, which can be attributed to
      shared epitopes between 2 of the 3 antigens. This new rMABbo-iELISA could be
      considered a simpler alternative to detect anti Babesia spp. antibodies and
      appears to be well suited to perform epidemiological surveys at the herd level in
      regions where ticks are present.

PMID- 29360802
TI  - A Novel Ruthenium-Decorating Polyoxomolybdate Cs3Na6H[MoVI14RuIV2O50(OH)2].24H2O:
      An Active Heterogeneous Oxidation Catalyst for Alcohols.
AB  - The first example of wholly inorganic ruthenium-containing polyoxomolybdate
      Cs3Na6H[MoVI14RuIV2O50(OH)2].24H2O (1) was isolated and systematically
      characterized by element analysis, infrared spectroscopy (IR), thermogravimetric
      analyses (TGA), X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray
      spectroscopy (EDX) and single-crystal X-ray diffraction. Compound 1 is composed
      of an unprecedented {Mo14}-type isopolymolybdate with a di-ruthenium core
      precisely encapsulated in its center, exhibiting a three-tiered ladder-like
      structure. The title compound can act as an efficient heterogeneous catalyst in
      the transformation of 1-phenylethanol to acetophenone. This catalyst is also
      capable of being recycled and reused for at least ten cycles with its activity
      being retained under the optimal conditions.

PMID- 29360800
TI  - Polymer Therapeutics: Biomarkers and New Approaches for Personalized Cancer
      Treatment.
AB  - Polymer therapeutics (PTs) provides a potentially exciting approach for the
      treatment of many diseases by enhancing aqueous solubility and altering drug
      pharmacokinetics at both the whole organism and subcellular level leading to
      improved therapeutic outcomes. However, the failure of many polymer-drug
      conjugates in clinical trials suggests that we may need to stratify patients in
      order to match each patient to the right PT. In this concise review, we hope to
      assess potential PT-specific biomarkers for cancer treatment, with a focus on new
      studies, detection methods, new models and the opportunities this knowledge will
      bring for the development of novel PT-based anti-cancer strategies. We discuss
      the various "hurdles" that a given PT faces on its passage from the syringe to
      the tumor (and beyond), including the passage through the bloodstream, tumor
      targeting, tumor uptake and the intracellular release of the active agent.
      However, we also discuss other relevant concepts and new considerations in the
      field, which we hope will provide new insight into the possible applications of
      PT-related biomarkers.

PMID- 29360803
TI  - Carbon Monoxide in Meat and Fish Packaging: Advantages and Limits.
AB  - Due to increased demands for greater expectation in relation to quality,
      convenience, safety and extended shelf-life, combined with growing demand from
      retailers for cost-effective extensions of fresh muscle foods' shelf-life, the
      food packaging industry quickly developed to meet these expectations. During the
      last few decades, modified atmosphere packaging (MAP) of foods has been a
      promising area of research, but much remains to be known regarding the use of
      unconventional gases such carbon monoxide (CO). The use of CO for meat and
      seafood packaging is not allowed in most countries due to the potential toxic
      effect, and its use is controversial in some countries. The commercial
      application of CO in food packaging was not then considered feasible because of
      possible environmental hazards for workers. CO has previously been reported to
      mask muscle foods' spoilage, and this was the primary concern raised for the
      prohibition, as this may mislead consumers. This review was undertaken to present
      the most comprehensive and current overview of the widely-available, scattered
      information about the use of CO in the preservation of muscle foods. The
      advantages of CO and its industrial limits are presented and discussed. The most
      recent literature on the consumer safety issues related to the use of CO and
      consumer acceptance of CO especially in meat packaging systems were also
      discussed. Recommendations and future prospects were addressed for food
      industries, consumers and regulators on what would be a "best practice" in the
      use of CO in food packaging. All this promotes high ethical standards in
      commercial communications by means of effective regulation, for the benefit of
      consumers and businesses in the world, and this implies that industrialized
      countries and members of their regulatory agencies must develop a coherent and
      robust systems of regulation and control that can respond effectively to new
      challenges.

PMID- 29360804
TI  - Does Use of Lidocaine Affect Culture of Synovial Fluid Obtained to Diagnose
      Periprosthetic Joint Infection (PJI)? An In Vitro Study.
AB  - BACKGROUND Synovial fluid culture (SFC) is recommended as one of the major
      diagnostic criteria by the Musculoskeletal Infection Society (MSIS) for
      diagnosing periprosthetic joint infection (PJI). Local anesthetic agents are used
      for anesthesia and analgesia in some clinical settings to relieve pain. As a
      local anesthetic, lidocaine is safely used in arthrocentesis to obtain synovial
      fluid. The goal of this study was to determine if infiltration anesthesia with
      additive-free lidocaine 2% has antibacterial effects that might interfere with
      subsequent SFC. MATERIAL AND METHODS Eight isolates of reference strains of
      Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hominis,
      Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus
      pyogenes, and Candida albicans were incubated on the plates. Each bacterial
      suspension was formed by 50-fold dilution before the test lidocaine 2% was added.
      For each strain, bacterial suspension was divided into 2 groups (5 samples each)
      exposed either lidocaine 2% or sterile non-bacteriostatic 0.45% saline. The
      antimicrobial property of lidocaine 2% was determined by measuring the bacterial
      density on agar plates incubated for 24 h and comparing it with controls
      unexposed to lidocaine 2%. RESULTS Exposure to lidocaine 2% negatively affected
      microbial viability in vitro. Of the lidocaine 2% exposure, reference strains but
      no Streptococcus pyogenes strain resulted in fewer colony-forming units compared
      with the sterile saline control. The antibacterial property of lidocaine 2%
      appears to affect the ability to culture the organism in synovial fluid.
      CONCLUSIONS Lidocaine 2% has strong antimicrobial activities against some
      commonly encountered bacterial strains in PJI. As a result, infiltration
      anesthesia with additive-free lidocaine 2% before the arthrocentesis procedure
      may affect the results of SFC. To further evaluate its potential antibacterial
      usefulness in clinical applications, studies are needed to assess the ability of
      lidocaine to reduce the risk of iatrogenic infections.

PMID- 29360805
TI  - Mild cerebellar injury does not significantly affect cerebral white matter
      microstructural organization and neurodevelopmental outcome in a contemporary
      cohort of preterm infants.
AB  - BackgroundPreterm birth is associated with an increased risk of cerebellar
      injury. The aim of this study was to assess the impact of cerebellar hemorrhages
      (CBH) on cerebral white matter microstructural tissue organization and cerebellar
      volume at term-equivalent age (TEA) in extremely preterm infants. Furthermore, we
      aimed to evaluate the association between CBH and neurodevelopmental outcome in
      late infancy.MethodsA total of 24 preterm infants with punctate CBH were included
      and each matched to two preterm control infants. T1-, T2-weighted images and
      diffusion-weighted imaging were acquired on a 3T magnetic resonance imaging (MRI)
      system. Regions of interest were drawn on a population-specific neonatal template
      and automatically registered to individual fractional anisotropy (FA) maps. Brain
      volumes were automatically computed. Neurodevelopmental outcome was assessed
      using the Bayley scales of Infant and Toddler Development at 2 years of corrected
      age.ResultsCBHs were not significantly related to FA in the posterior limb of the
      internal capsule and corpus callosum or to cerebellar volume. Infants with CBH
      did not have poorer neurodevelopmental outcome compared with control
      infants.ConclusionThese findings suggest that the impact of mild CBH on early
      macroscale brain development may be limited. Future studies are needed to assess
      the effects of CBH on long-term neurodevelopment.

PMID- 29360806
TI  - Birth size, body composition, and adrenal androgens as determinants of bone
      mineral density in mid-childhood.
AB  - BackgroundBirth weight has an impact on adult bone mass. Higher birth weight is
      associated with greater bone mineral content (BMC) and children born small for
      gestational age (SGA) are at an increased risk for impaired accrual of bone mass.
      Our aim was to study whether the impact of birth size or early childhood growth
      on bone mass is visible already in mid-childhood.MethodsWe studied 49 children
      born large for gestational age (LGA), 56 children born appropriate for
      gestational age (AGA), and 23 children born SGA at 5.0-8.7 years of age. Body
      composition was assessed by whole-body dual-energy X-ray absorptiometry. Fasting
      blood samples and anthropometric data were collected.ResultsThe children born SGA
      had lower bone mineral density (BMD) Z-score (P<0.001) and age- and sex-adjusted
      BMD (P<0.005) than the LGA and AGA children. Adjusted BMC, muscle mass, and body
      fat percentage (%BF) did not differ between the study groups. Muscle mass, BMI SD
      score (SDS), %BF, and serum dehydroepiandrosterone sulfate (DHEAS) concentration
      were the strongest predictors of high BMD in mid-childhood.ConclusionSGA-born
      children had lower BMD in mid-childhood compared with AGA- and LGA-born ones.
      Muscle mass or BMI SDS, %BF, and DHEAS were significant predictors of childhood
      BMD.

PMID- 29360807
TI  - Antiproteinuric effect of an endothelin-1 receptor antagonist in puromycin
      aminonucleoside-induced nephrosis in rat.
AB  - BackgroundThe pathogenesis of idiopathic nephrotic syndrome (INS) remains
      unclear, although recent studies suggest endothelin 1 (ET-1) and CD80 of
      podocytes are involved. We investigated the potential of antagonist to ET-1
      receptor type A (ETRA) as therapeutic agent through the suppression of CD80 in a
      rat model of INS.MethodsPuromycin aminonucleoside (PAN) was injected to Wister
      rats to induce proteinuria: some were treated with ETRA antagonist and others
      were treated with 0.5% methylcellulose. Blood and tissue samples were collected.
      Quantitative PCR was used to determine the expression of Toll-like receptor-3
      (TLR-3), nuclear factor-kappaB (NF-kappaB), CD80, talin, ETRA, and ET-1 in the
      kidney. To confirm the level of CD80 protein expression, immunofluorescence
      staining and western blot analysis of the renal tissue were
      performed.ResultsAmount of proteinuria in the treatment group was significantly
      lower than the other groups. The same-day body weight, serum creatinine values,
      and blood pressure were not significantly different. ETRA antagonist restores
      podocyte foot process effacement as well as the aberrant expression of TLR-3,
      nuclear factor-kappaB (NF-kappaB), and CD80 in PAN-injured kidneys.ConclusionsThe
      ETRA antagonist may be promising drug for INS as it showed an antiproteinuric
      effect. Its action was considered to be through suppression of CD80 expression on
      podocytes.

PMID- 29360808
TI  - Serum levels of C1q/tumor necrosis factor-related protein-1 in children with
      Kawasaki disease.
AB  - BackgroundTo investigate the serum C1q/tumor necrosis factor-related protein-1
      (CTRP1) levels in children with acute Kawasaki disease (KD), as well as the
      relationship between CTRP1 levels and laboratory variables.MethodsEighty-seven
      children with KD and 38 healthy controls (HCs) were included in this study.
      General characteristics were obtained from all subjects. Serum CTRP1 levels in
      all subjects and serum tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta
      (IL-1beta), and interleukin-6 (IL-6) levels in KD patients were measured using
      enzyme-linked immunosorbent assay.ResultsCompared with the HC group, serum CTRP1
      levels were significantly elevated in the KD group. Significantly higher serum
      TNF-alpha, IL-1beta, IL-6, and CTRP1 levels were observed in patients with KD
      with coronary artery lesions (KD-CALs) than in patients with KD without CALs (KD
      NCALs). Serum CTRP1 levels were positively correlated with white blood cell
      counts (WBC), percentage of neutrophils (N%), thrombin time (TT), procalcitonin
      (Pct), TNF-alpha, IL-1beta, and IL-6 levels. Meanwhile, CTRP1 levels were
      negatively correlated with the percentage of leukomonocytes (L%) in KD patients.
      Furthermore, serum CTRP1 levels were positively correlated with the time point of
      intravenous immunoglobulin (IVIG), WBC, N%, TNF-alpha, IL-1beta, and IL-6 levels
      in the KD-CAL group.ConclusionCTRP1 may participate in the process of vasculitis
      and blood coagulation during the acute phase of KD.

PMID- 29360809
TI  - Targeting the PXR-TLR4 signaling pathway to reduce intestinal inflammation in an
      experimental model of necrotizing enterocolitis.
AB  - BackgroundThere is substantial evidence that signaling through Toll-like receptor
      4 (TLR4) contributes to the pathogenesis of necrotizing enterocolitis (NEC).
      Pregnane X receptor (PXR), a xenobiotic sensor and signaling intermediate for
      certain host-bacterial metabolites, has been shown to negatively regulate TLR4
      signaling. Here we investigated the relationship between PXR and TLR4 in the
      developing murine intestine and explored the capacity of PXR to modulate
      inflammatory pathways involved in experimental NEC.MethodsWild-type and PXR-/-
      mice were studied at various time points of development in an experimental model
      of NEC. In addition, we studied the ability of the secondary bile acid
      lithocholic acid (LCA), a known PXR agonist in liver, to activate intestinal PXR
      and reduce NEC-related intestinal inflammation.ResultsWe found a reciprocal
      relationship between the developmental expression of PXR and TLR4 in wild-type
      murine intestine, with PXR acting to reduce TLR4 expression by decreasing TLR4
      mRNA stability. In addition, PXR-/- mice exhibited a remarkably heightened
      severity of disease in experimental NEC. Moreover, LCA attenuated intestinal
      proinflammatory responses in the early stages of experimental NEC.ConclusionThese
      findings provide proactive insights into the regulation of TLR4 in the developing
      intestine. Targeting PXR may be a novel approach for NEC prevention.

PMID- 29360810
TI  - Back from the dead: TIL apoptosis in cancer immune evasion.

PMID- 29360811
TI  - Comment on 'Human papillomavirus association is the most important predictor for
      surgically treated patients with oropharyngeal cancer'.

PMID- 29360812
TI  - Domestic light at night and breast cancer risk: a prospective analysis of 105 000
      UK women in the Generations Study.
AB  - BACKGROUND: Circadian disruption caused by exposure to light at night (LAN) has
      been proposed as a risk factor for breast cancer and a reason for secular
      increases in incidence. Studies to date have largely been ecological or case
      control in design and findings have been mixed. METHODS: We investigated the
      relationship between LAN and breast cancer risk in the UK Generations Study.
      Bedroom light levels and sleeping patterns at age 20 and at study recruitment
      were obtained by questionnaire. Analyses were conducted on 105 866 participants
      with no prior history of breast cancer. During an average of 6.1 years of follow
      up, 1775 cases of breast cancer were diagnosed. Cox proportional hazard models
      were used to calculate hazard ratios (HRs), adjusting for potential confounding
      factors. RESULTS: There was no association between LAN level and breast cancer
      risk overall (highest compared with lowest LAN level at recruitment: HR=1.01, 95%
      confidence interval (CI): 0.88-1.15), or for invasive (HR=0.98, 95% CI: 0.85
      1.13) or in situ (HR=0.96, 95% CI: 0.83-1.11) breast cancer, or oestrogen
      receptor (ER) positive (HR=0.98, 95% CI: 0.84-1.14); or negative (HR=1.16, 95%
      CI: 0.82-1.65) tumours separately. The findings did not differ by menopausal
      status. Adjusting for sleep duration, sleeping at unusual times (non-peak sleep)
      and history of night work did not affect the results. Night waking with exposure
      to light, occurring around age 20, was associated with a reduced risk of
      premenopausal breast cancer (HR for breast cancer overall=0.74, 95% CI: 0.55
      0.99; HR for ER-positive breast cancer=0.69, 95% CI: 0.49-0.97). CONCLUSIONS: In
      this prospective cohort analysis of LAN, there was no evidence that LAN exposure
      increased the risk of subsequent breast cancer, although the suggestion of a
      lower breast cancer risk in pre-menopausal women with a history of night waking
      in their twenties may warrant further investigation.

PMID- 29360813
TI  - Development and validation of a plasma-based melanoma biomarker suitable for
      clinical use.
AB  - This corrects the article DOI: 10.1038/bjc.2017.85.

PMID- 29360814
TI  - Postmenopausal breast cancer and oestrogen associations with the IgA-coated and
      IgA-noncoated faecal microbiota.
AB  - BACKGROUND: The diversity and composition of the gut microbiota may affect breast
      cancer risk by modulating systemic levels of oestrogens and inflammation. The
      current investigation tested this hypothesis in postmenopausal women by
      identifying breast cancer associations with an inflammation marker, oestrogen
      levels, and faecal microbes that were or were not coated with mucosal
      immunoglobulin A (IgA). METHODS: In this population-based study, we compared 48
      postmenopausal breast cancer cases (75% stage 0-1, 88% oestrogen-receptor
      positive) to 48 contemporaneous, postmenopausal, normal-mammogram, age-matched
      controls. Microbiota metrics employed 16S rRNA gene amplicon sequencing from IgA
      coated and -noncoated faecal microbes. High-performance liquid
      chromatography/mass spectrometry (HPLC/MS) and radioimmunoassay were used to
      quantify urine prostaglandin E metabolite (PGE-M), a possible marker of
      inflammation; urine oestrogens and oestrogen metabolites were quantified by
      HPLC/MS-MS. RESULTS: Women with pre-treatment breast cancer had non-significantly
      elevated oestrogen levels; controls' (but not cases') oestrogens were directly
      correlated with their IgA-negative microbiota alpha diversity (P=0.012).
      Prostaglandin E metabolite levels were not associated with case status, oestrogen
      levels, or alpha diversity. Adjusted for oestrogens and other variables, cases
      had significantly reduced alpha diversity and altered composition of both their
      IgA-positive and IgA-negative faecal microbiota. Cases' faecal microbial IgA
      positive imputed Immune System Diseases metabolic pathway genes were increased;
      also, cases' IgA-positive and IgA-negative imputed Genetic Information Processing
      pathway genes were decreased (P?0.01). CONCLUSIONS: Compared to controls, breast
      cancer cases had significant oestrogen-independent associations with the IgA
      positive and IgA-negative gut microbiota. These suggest that the gut microbiota
      may influence breast cancer risk by altered metabolism, oestrogen recycling, and
      immune pressure.

PMID- 29360815
TI  - KRAS mutations in cell-free DNA from preoperative and postoperative sera as a
      pancreatic cancer marker: a retrospective study.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has very poor prognosis
      despite existing multimodal therapies. This study aimed to investigate whether
      KRAS mutations at codons 12/13 in cell-free DNA (cfDNA) from preoperative and
      postoperative sera from patients with PDAC can serve as a predictive biomarker
      for treatment response and outcomes after surgery. METHODS: Preoperative and
      postoperative serum samples obtained from 45 patients with PDAC whom underwent
      curative pancreatectomy at our institution between January 2013 and July 2016
      were retrospectively analysed. Peptide nucleic acid-directed PCR clamping was
      used to identify KRAS mutations in cfDNA. RESULTS: Among the 45 patients
      enrolled, 11 (24.4%) and 20 (44.4%) had KRAS mutations in cfDNA from preoperative
      and postoperative sera, respectively. Multivariate analysis revealed that KRAS
      mutations in postoperative serum (hazard ratio (HR)=2.919; 95% confidence
      interval (CI)=1.109-5.621; P=0.027) are an independent prognostic factor for
      disease-free survival. Furthermore, the shift from wild-type KRAS in preoperative
      to mutant KRAS in postoperative cfDNA (HR=9.419; 95% Cl=2.015-44.036; P=0.004)
      was an independent prognostic factor for overall survival. CONCLUSIONS: Changes
      in KRAS mutation status between preoperative and postoperative cfDNA may be a
      useful predictive biomarker for survival and treatment response.

PMID- 29360816
TI  - Loss in working years after a breast cancer diagnosis.
AB  - BACKGROUND: Breast cancer can negatively influence working life, but it is
      unclear how many working years women with breast cancer can expect to lose.
      METHODS: Women diagnosed with breast cancer between 1997 and 2012 were identified
      in the Breast Cancer Data Base Sweden (N=19 661), together with breast cancer
      free comparison women (N=81 303). Using flexible parametric survival modelling,
      the loss in working years was calculated as the difference in the remaining years
      in the work force between women with and without breast cancer. RESULTS: Women
      aged 50 years at diagnosis with stage I disease lost on average 0.5 years (95%
      CI, 0.2-0.7) of their remaining working time; the corresponding estimates were
      0.9 years (0.5-1.2) in stage II, 2.5 years (1.9-3.1) in stage III and 8.1 years
      (6.5-9.7) in stage IV. Women with in situ breast cancer did not lose any working
      years. The strongest treatment determinant was axillary lymph node dissection.
      CONCLUSIONS: We found a loss in working years not only in late but also in early
      stage breast cancer. Although it is reassuring that some groups had no or only a
      modest work loss, the economic consequences for society are considerable given
      the large number of women annually diagnosed with breast cancer.

PMID- 29360817
TI  - Reply to 'Comment on 'Human papillomavirus association is the most important
      predictor for surgically treated patients with oropharyngeal cancer".

PMID- 29360818
TI  - A novel Epstein-Barr virus-latent membrane protein-1-specific T-cell receptor for
      TCR gene therapy.
AB  - BACKGROUND: Adoptive transfer of genetically engineered T-cells to express
      antigen-specific T-cell receptor (TCR) is a feasible and effective therapeutic
      approach for numerous types of cancers, including Epstein-Barr virus (EBV)
      associated malignancies. Here, we describe a TCR gene transfer regimen to rapidly
      and reliably generate T-cells specific to EBV-encoded latent membrane protein-1
      (LMP1), which is a potential target for T-cell-based immunotherapy. METHODS: A
      novel TCR specific to LMP1 (LMP1-TCR) was isolated from HLA-A*0201 transgenic
      mice that were immunised with the minimal epitope LMP1166 (TLLVDLLWL), and LMP1
      TCR-transduced peripheral blood lymphocytes were evaluated for functional
      specificities. RESULTS: Both human CD8 and CD4 T-cells expressing the LMP1-TCR
      provoked high levels of cytokine secretion and cytolytic activity towards peptide
      pulsed and LMP1-expressing tumour cells. Notably, recognition of these T-cells to
      peptide-pulsed cells was maintained at low concentration of peptide, implying
      that the LMP1-TCR has high avidity. Infusion of these engineered T-cells revealed
      remarkable therapeutic effects and inhibition of tumour growth in a preclinical
      xenogeneic model. We observed explosive ex vivo proliferation of functional TCR
      transduced T-cells with artificial antigen-presenting cells that express co
      stimulatory molecules CD80 and 4-1BBL. CONCLUSIONS: These data suggest that the
      novel TCR-targeting LMP1 might allow the potential design of T-cell-based
      immunotherapeutic strategies against EBV-positive malignancies.

PMID- 29360819
TI  - A core matrisome gene signature predicts cancer outcome.
AB  - BACKGROUND: Accumulating evidence implicates the tumour stroma as an important
      determinant of cancer progression but the protein constituents relevant for this
      effect are unknown. Here we utilised a bioinformatics approach to identify an
      extracellular matrix (ECM) gene signature overexpressed in multiple cancer types
      and strongly predictive of adverse outcome. METHODS: Gene expression levels in
      cancers were determined using Oncomine. Geneset enrichment analysis was performed
      using the Broad Institute desktop application. Survival analysis was performed
      using KM plotter. Survival data were generated from publically available
      genesets. RESULTS: We analysed ECM genes significantly upregulated across a large
      cohort of patients with ovarian, lung, gastric and colon cancers and defined a
      signature of nine commonly upregulated genes. Each of these nine genes was
      considerably overexpressed in all the cancers studied, and cumulatively, their
      expression was associated with poor prognosis across all data sets. Further, the
      gene signature expression was associated with enrichment of genes governing
      processes linked to poor prognosis, such as EMT, angiogenesis, hypoxia, and
      inflammation. CONCLUSIONS: Here we identify a nine-gene ECM signature, which
      strongly predicts outcome across multiple cancer types and can be used for
      prognostication after validation in prospective cancer cohorts.

PMID- 29360822
TI  - ViroFind: A novel target-enrichment deep-sequencing platform reveals a complex JC
      virus population in the brain of PML patients.
AB  - Deep nucleotide sequencing enables the unbiased, broad-spectrum detection of
      viruses in clinical samples without requiring an a priori hypothesis for the
      source of infection. However, its use in clinical research applications is
      limited by low cost-effectiveness given that most of the sequencing information
      from clinical samples is related to the human genome, which renders the analysis
      of viral genomes challenging. To overcome this limitation we developed ViroFind,
      an in-solution target-enrichment platform for virus detection and discovery in
      clinical samples. ViroFind comprises 165,433 viral probes that cover the genomes
      of 535 selected DNA and RNA viruses that infect humans or could cause zoonosis.
      The ViroFind probes are used in a hybridization reaction to enrich viral
      sequences and therefore enhance the detection of viral genomes via deep
      sequencing. We used ViroFind to detect and analyze all viral populations in the
      brain of 5 patients with progressive multifocal leukoencephalopathy (PML) and of
      18 control subjects with no known neurological disease. Compared to direct deep
      sequencing, by using ViroFind we enriched viral sequences present in the clinical
      samples up to 127-fold. We discovered highly complex polyoma virus JC populations
      in the PML brain samples with a remarkable degree of genetic divergence among the
      JC virus variants of each PML brain sample. Specifically for the viral capsid
      protein VP1 gene, we identified 24 single nucleotide substitutions, 12 of which
      were associated with amino acid changes. The most frequent (4 of 5 samples, 80%)
      amino acid change was D66H, which is associated with enhanced tissue tropism, and
      hence likely a viral fitness advantage, compared to other variants. Lastly, we
      also detected sparse JC virus sequences in 10 of 18 (55.5%) of control samples
      and sparse human herpes virus 6B (HHV6B) sequences in the brain of 11 of 18
      (61.1%) control subjects. In sum, ViroFind enabled the in-depth analysis of all
      viral genomes in PML and control brain samples and allowed us to demonstrate a
      high degree of JC virus genetic divergence in vivo that has been previously
      underappreciated. ViroFind can be used to investigate the structure of the virome
      with unprecedented depth in health and disease state.

PMID- 29360821
TI  - Patterns of zolpidem use among Iraq and Afghanistan veterans: A retrospective
      cohort analysis.
AB  - BACKGROUND: Although concern exists regarding the adverse effects and rate of
      zolpidem use, especially long-term use, limited information is available
      concerning patterns of zolpidem use. OBJECTIVE: To examine the prevalence and
      correlates of zolpidem exposure in Iraq and Afghanistan Veterans (IAVs). METHODS:
      A retrospective cohort study of zolpidem prescriptions was performed with
      National Veterans Health Administration (VHA) data. We gathered national VA
      inpatient, outpatient, and pharmacy data files for IAV's who received VA care
      between fiscal years (FY) 2013 and 2014. The VA pharmacy database was used to
      identify the prevalence of long term (>30 days), high-dose zolpidem exposure
      (>10mg immediate-release; >12.5mg extended-release) and other medications
      received in FY14. Baseline characteristics (demographics, diagnoses) were
      identified in FY13. Bivariate and multivariable analyses were used to examine the
      demographic, clinical, and medication correlates of zolpidem use. RESULTS: Of
      493,683 IAVs who received VHA care in FY 2013 and 2014, 7.6% (n = 37,422) were
      prescribed zolpidem in FY 2014. Women had lower odds of high-dose zolpidem
      exposure than men. The majority (77.3%) of IAVs who received zolpidem
      prescriptions had long-term use with an average days' supply of 189.3 days and a
      minority (0.9%) had high-dose exposure. In multivariable analyses, factors
      associated with long-term zolpidem exposure included age greater than 29 years
      old, PTSD, insomnia, Selim Index, physical 2-3 conditions, opioids,
      antidepressants, benzodiazepines, atypical antipsychotics, and stimulants. High
      dose exposure was associated with PTSD, depression, substance use disorder,
      insomnia, benzodiazepines, atypical antipsychotics, and stimulant prescriptions.
      CONCLUSION: The current practices of insomnia pharmacotherapy in IAVs fall short
      of the clinical guidelines and may reflect high-risk zolpidem prescribing
      practices that put Iraq and Afghanistan Veterans at risk for adverse effects of
      zolpidem and poor health outcomes.

PMID- 29360820
TI  - Dynamic genome wide expression profiling of Drosophila head development reveals a
      novel role of Hunchback in retinal glia cell development and blood-brain barrier
      integrity.
AB  - Drosophila melanogaster head development represents a valuable process to study
      the developmental control of various organs, such as the antennae, the dorsal
      ocelli and the compound eyes from a common precursor, the eye-antennal imaginal
      disc. While the gene regulatory network underlying compound eye development has
      been extensively studied, the key transcription factors regulating the formation
      of other head structures from the same imaginal disc are largely unknown. We
      obtained the developmental transcriptome of the eye-antennal discs covering late
      patterning processes at the late 2nd larval instar stage to the onset and
      progression of differentiation at the end of larval development. We revealed the
      expression profiles of all genes expressed during eye-antennal disc development
      and we determined temporally co-expressed genes by hierarchical clustering. Since
      co-expressed genes may be regulated by common transcriptional regulators, we
      combined our transcriptome dataset with publicly available ChIP-seq data to
      identify central transcription factors that co-regulate genes during head
      development. Besides the identification of already known and well-described
      transcription factors, we show that the transcription factor Hunchback (Hb)
      regulates a significant number of genes that are expressed during late
      differentiation stages. We confirm that hb is expressed in two polyploid
      subperineurial glia cells (carpet cells) and a thorough functional analysis shows
      that loss of Hb function results in a loss of carpet cells in the eye-antennal
      disc. Additionally, we provide for the first time functional data indicating that
      carpet cells are an integral part of the blood-brain barrier. Eventually, we
      combined our expression data with a de novo Hb motif search to reveal stage
      specific putative target genes of which we find a significant number indeed
      expressed in carpet cells.

PMID- 29360823
TI  - Population-based estimate of hepatitis C virus prevalence in Ontario, Canada.
AB  - BACKGROUND: Hepatitis C virus (HCV) is the most burdensome infectious illness in
      Canada. Current screening strategies miss a significant proportion of cases,
      leaving many undiagnosed. Elevated HCV prevalence in those born between 1945 and
      1965 has prompted calls for birth-cohort screening in this group. However, Canada
      lacks population-level data to support this recommendation. We performed a
      serosurvey to obtain population-based HCV prevalence estimates in Ontario
      residents born between 1945-1974, to generate evidence for birth-cohort screening
      recommendations. METHODS: We tested anonymized residual sera in five-year age-sex
      bands from Ontario for anti-HCV antibody. We performed descriptive
      epidemiological analysis and used a logistic regression model to determine HCV
      risk-factors. RESULTS: Of 10,006 sera analyzed, 155 (1.55%, 95% confidence
      interval (CI) 1.32, 1.81) were positive for HCV antibody. Individuals born
      between 1950-1964 had a significantly higher combined prevalence of 1.92% (95% CI
      1.56, 2.34) compared to 1.14% (95% CI 0.69, 1.77) (p = 0.04) for those born
      between 1970-1974. For males, comprising 107/155 (69.03%) of positive samples,
      the highest prevalence was 3.00% (95% CI 1.95, 4.39) for the 1960-1964 birth
      cohort. For females, the highest prevalence was 1.56% (95% CI 0.83, 2.65) for
      those born between 1955-1959. Male sex was significantly associated with positive
      HCV serostatus. INTERPRETATION: HCV prevalence in Ontario is highest among those
      in this birth cohort, and higher than previous estimates. The prevalence
      estimates presented in our study provide important data to underpin birth-cohort
      screening recommendations.

PMID- 29360824
TI  - Compact FPGA hardware architecture for public key encryption in embedded devices.
AB  - Security is a crucial requirement in the envisioned applications of the Internet
      of Things (IoT), where most of the underlying computing platforms are embedded
      systems with reduced computing capabilities and energy constraints. In this paper
      we present the design and evaluation of a scalable low-area FPGA hardware
      architecture that serves as a building block to accelerate the costly operations
      of exponentiation and multiplication in [Formula: see text], commonly required in
      security protocols relying on public key encryption, such as in key agreement,
      authentication and digital signature. The proposed design can process operands of
      different size using the same datapath, which exhibits a significant reduction in
      area without loss of efficiency if compared to representative state of the art
      designs. For example, our design uses 96% less standard logic than a similar
      design optimized for performance, and 46% less resources than other design
      optimized for area. Even using fewer area resources, our design still performs
      better than its embedded software counterparts (190x and 697x).

PMID- 29360825
TI  - Correction: Alkaline Ceramidase 3 Deficiency Results in Purkinje Cell
      Degeneration and Cerebellar Ataxia Due to Dyshomeostasis of Sphingolipids in the
      Brain.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1005591.].

PMID- 29360826
TI  - Epithelial to mesenchymal transition in human endocrine islet cells.
AB  - BACKGROUND: beta-cells undergo an epithelial to mesenchymal transition (EMT) when
      expanded in monolayer culture and give rise to highly proliferative mesenchymal
      cells that retain the potential to re-differentiate into insulin-producing cells.
      OBJECTIVE: To investigate whether EMT takes place in the endocrine non-beta cells
      of human islets. METHODOLOGY: Human islets isolated from 12 multiorgan donors
      were dissociated into single cells, purified by magnetic cell sorting, and
      cultured in monolayer. RESULTS: Co-expression of insulin and the mesenchymal
      marker vimentin was identified within the first passage (p1) and increased
      subsequently (insulin+vimentin+ 7.2+/-6% at p1; 43+/-15% at p4). The endocrine
      non-beta-cells did also co-express vimentin (glucagon+vimentin+ 59+/-1.5% and
      93+/-6%, somatostatin+vimentin+ 16+/-9.4% and 90+/-10% at p1 and p4 respectively;
      PP+vimentin+ 74+/-14% at p1; 88+/-12% at p2). The percentage of cells expressing
      only endocrine markers was progressively reduced (0.6+/-0.2% insulin+, 0.2+/-0.1%
      glucagon+, and 0.3+/-0.2% somatostatin+ cells at p4, and 0.7+/-0.3% PP+ cells at
      p2. Changes in gene expression were also indicated of EMT, with reduced
      expression of endocrine markers and the epithelial marker CDH-1 (p<0.01), and
      increased expression of mesenchymal markers (CDH-2, SNAI2, ZEB1, ZEB2, VIM, NT5E
      and ACTA2; p<0.05). Treatment with the EMT inhibitor A83-01 significantly reduced
      the percentage of co-expressing cells and preserved the expression of endocrine
      markers. CONCLUSIONS: In adult human islets, all four endocrine islet cell types
      undergo EMT when islet cells are expanded in monolayer conditions. The presence
      of EMT in all islet endocrine cells could be relevant to design of strategies
      aiming to re-differentiate the expanded islet cells towards a beta-cell
      phenotype.

PMID- 29360827
TI  - CXCL1 induces senescence of cancer-associated fibroblasts via autocrine loops in
      oral squamous cell carcinoma.
AB  - Cancer-associated fibroblasts (CAFs) have emerged as one of the main factors
      related to cancer progression, however, the conversion mechanism of normal
      fibroblasts (NOFs) to CAFs has not been well elucidated. The aim of this study
      was to investigate the underlying mechanism of CAF transformation from NOFs in
      oral squamous cell carcinoma (OSCC). This study found that NOFs exposed to OSCC
      cells transformed to senescent cells. The cytokine antibody array showed the
      highest secretion levels of IL-6 and CXCL1 in NOFs co-cultured with OSCC cells.
      Despite that both IL-6 and CXCL1 induced the senescent phenotype of CAFs, CXCL1
      secretion showed a cancer-specific response to transform NOFs into CAFs in OSCC,
      whereas IL-6 secretion was eventuated by common co-culture condition. Further,
      CXCL1 was released from NOFs co-cultured with OSCC cells, however, CXCL1 was
      undetectable in mono-cultured NOFs or co-cultured OSCC cells with NOFs. Taken
      together, this study demonstrates that CXCL1 can transform NOFs into senescent
      CAFs via an autocrine mechanism. These data might contribute to further
      understanding of CAFs and to development of a potential therapeutic approach
      targeting cancer cells-CAFs interactions.

PMID- 29360828
TI  - The inter- and intra- generational transmission of family poverty and hardship
      (adversity): A prospective 30 year study.
AB  - BACKGROUND: Children exposed to family poverty have been found to have higher
      morbidity and mortality rates, poorer mental health and cognitive outcomes and
      reduced life chances across a wide range of life domains. There is, however, very
      little known about the extent to which poverty is experienced by children over
      their early life course, particularly in community samples. This study tracks
      changes in family poverty and the main factors that predict family poverty
      (adverse life experiences) over a 30-year period since the birth of the study
      child. METHODS: Data are from a prospective, longitudinal, birth cohort study
      conducted in Brisbane, Australia. Consecutive families were recruited at the
      mothers' first obstetrical visit at one of two major obstetrical hospitals in
      Brisbane. Data are available for 2087 families with complete data at the 30-year
      follow-up. Poverty was measured using family income at each time point (adjusted
      for inflation). FINDINGS: Poverty affects about 20% of families at any time
      point. It is common for families to move in and out of poverty, as their
      circumstances are affected by such adversities as unemployment and marital
      breakdown. Over the period of the study about half the families in the study
      experienced poverty on at least one occasion. Only a very small minority of
      families experienced persistent poverty over the 30-year duration of the study.
      Logistic regressions with time lag show that family poverty predicts subsequent
      adversities and adverse events predict subsequent poverty. CONCLUSIONS:
      Experiences of poverty and adversity are common and may vary greatly over the
      child's early life course. In assessing the health consequences of poverty, it is
      important to distinguish the timing and chronicity of early life course
      experiences of poverty and adversity.

PMID- 29360829
TI  - Long-term risks and benefits associated with cesarean delivery for mother, baby,
      and subsequent pregnancies: Systematic review and meta-analysis.
AB  - BACKGROUND: Cesarean birth rates continue to rise worldwide with recent (2016)
      reported rates of 24.5% in Western Europe, 32% in North America, and 41% in South
      America. The objective of this systematic review is to describe the long-term
      risks and benefits of cesarean delivery for mother, baby, and subsequent
      pregnancies. The primary maternal outcome was pelvic floor dysfunction, the
      primary baby outcome was asthma, and the primary subsequent pregnancy outcome was
      perinatal death. METHODS AND FINDINGS: Medline, Embase, Cochrane, and Cumulative
      Index to Nursing and Allied Health Literature (CINAHL) databases were
      systematically searched for published studies in human subjects (last search 25
      May 2017), supplemented by manual searches. Included studies were randomized
      controlled trials (RCTs) and large (more than 1,000 participants) prospective
      cohort studies with greater than or equal to one-year follow-up comparing
      outcomes of women delivering by cesarean delivery and by vaginal delivery. Two
      assessors screened 30,327 abstracts. Studies were graded for risk of bias by two
      assessors using the Scottish Intercollegiate Guideline Network (SIGN) Methodology
      Checklist and the Risk of Bias Assessment tool for Non-Randomized Studies.
      Results were pooled in fixed effects meta-analyses or in random effects models
      when significant heterogeneity was present (I2 >= 40%). One RCT and 79 cohort
      studies (all from high income countries) were included, involving 29,928,274
      participants. Compared to vaginal delivery, cesarean delivery was associated with
      decreased risk of urinary incontinence, odds ratio (OR) 0.56 (95% CI 0.47 to
      0.66; n = 58,900; 8 studies) and pelvic organ prolapse (OR 0.29, 0.17 to 0.51; n
      = 39,208; 2 studies). Children delivered by cesarean delivery had increased risk
      of asthma up to the age of 12 years (OR 1.21, 1.11 to 1.32; n = 887,960; 13
      studies) and obesity up to the age of 5 years (OR 1.59, 1.33 to 1.90; n = 64,113;
      6 studies). Pregnancy after cesarean delivery was associated with increased risk
      of miscarriage (OR 1.17, 1.03 to 1.32; n = 151,412; 4 studies) and stillbirth (OR
      1.27, 1.15 to 1.40; n = 703,562; 8 studies), but not perinatal mortality (OR
      1.11, 0.89 to 1.39; n = 91,429; 2 studies). Pregnancy following cesarean delivery
      was associated with increased risk of placenta previa (OR 1.74, 1.62 to 1.87; n =
      7,101,692; 10 studies), placenta accreta (OR 2.95, 1.32 to 6.60; n = 705,108; 3
      studies), and placental abruption (OR 1.38, 1.27 to 1.49; n = 5,667,160; 6
      studies). This is a comprehensive review adhering to a registered protocol, and
      guidelines for the Meta-analysis of Observational Studies in Epidemiology were
      followed, but it is based on predominantly observational data, and in some meta
      analyses, between-study heterogeneity is high; therefore, causation cannot be
      inferred and the results should be interpreted with caution. CONCLUSIONS: When
      compared with vaginal delivery, cesarean delivery is associated with a reduced
      rate of urinary incontinence and pelvic organ prolapse, but this should be
      weighed against the association with increased risks for fertility, future
      pregnancy, and long-term childhood outcomes. This information could be valuable
      in counselling women on mode of delivery.

PMID- 29360830
TI  - Effects of dietary supplementation of arginine-silicate-inositol complex on
      absorption and metabolism of calcium of laying hens.
AB  - The effects of supplementation of arginine-silicate-inositol complex (ASI; 49.5
      8.2-25 g/kg, respectively) to laying hens were investigated with respect to
      eggshell quality, calcium (Ca) balance, and expression of duodenal proteins
      related to Ca metabolism (calbindin and tight junction proteins). A total of 360
      laying hens, 25 weeks old, were divided into 3 groups consisting of 6 replicate
      of cages, 20 birds per cage. The groups were fed a basal diet and the basal diet
      supplemented with 500 or 1000 mg ASI complex per kilogram for 90 days. Data were
      analyzed by ANCOVA using data during the first week of the adaptation period as
      covariates. As the ASI complex supplementation level increased, there were
      increases in feed intake (P < 0.0001), egg production (P < 0.001), egg weight (P
      < 0.0001) and eggshell weight (P < 0.001) weight, and shell thickness (P < 0.001)
      and decreases in feed conversion ratio and cracked egg percentage (P < 0.0001 for
      both). Concentrations of serum osteocalcin (P < 0.0001), vitamin D (P < 0.0001),
      calcium (P < 0.001), phosphorus (P < 0.001), and alkaline phosphatase (P < 0.008)
      as well as amounts of calcium retention (P < 0.0001) and eggshell calcium
      deposition (P < 0.001), and Ca balance (P < 0.0001) increased, whereas amount of
      calcium excretion (P < 0.001) decreased linearly in a dose-dependent manner. The
      ASI complex supplementation increased expressions of calcium transporters
      (calbindin-D28k, N sodium-calcium exchanger, plasma membrane calcium ATPase, and
      vitamin D receptor) and tight junction proteins (zonula occludens-1 and occludin)
      in the duodenum in a linear fashion (P < 0.0001 for all). In conclusion,
      provision of dietary ASI complex to laying hens during the peak laying period
      improved eggshell quality through improving calcium utilization as reflected by
      upregulation of genes related to the calcium metabolism. Further studies are
      needed to elucidate the contribution of each of the ASI complex ingredients.

PMID- 29360831
TI  - Morphologically indistinguishable hybrid Carassius female with 156 chromosomes: A
      threat for the threatened crucian carp, C. carassius, L.
AB  - The crucian carp Carassius carassius (Linnaeus, 1758), is native to many European
      freshwaters. Despite its wide distribution, the crucian carp is declining in both
      the number and sizes of populations across much of its range. Here we studied 30
      individuals of a putative pure population from Helsinki, Finland. Despite clear
      external morphological features of C. carassius, an individual was of a higher
      ploidy level than the others. We therefore applied a set of molecular genetic (S7
      nuclear and cytochrome b mitochondrial genes) and cytogenetic tools (sequential
      fluorescent 4', 6-diamidino-2-phenylindole [DAPI], Chromomycin A3 [CMA3], C
      banding and in situ hybridization [FISH] with both 5S and 28S ribosomal DNA
      probes) to determine its origin. While all examined characteristics of a diploid
      representative male (CCAHe2Fi) clearly corresponded to those of C. carassius, a
      triploid individual (CCAHe1Fi) was more complex. Phylogenetic analysis revealed
      that the nuclear genome of CCAHe1Fi contained three haploid sets: two C. gibelio
      and one C. carassius. However the mitochondrial DNA was that of C. gibelio,
      demonstrating its hybrid origin. The FISH revealed three strong (more intensive)
      5S rDNA loci, confirming the triploid status, and an additional 24 weak (less
      intensive) signals were observed in the chromosome complement of CCAHe1Fi. On the
      other hand, only two strong and 16 weak 5S rDNA signals were visible on the
      chromosomes of the CCAHe2Fi male. 28S rDNA FISH revealed four strong signals in
      both CCAHe1Fi and CCAHe2Fi individuals. CMA3 staining revealed four to six CMA3
      positive bands of CCAHe1Fi, while that of diploids contained only two to four.
      The fact that a polyploid hybrid Carassius female with a strong invasive
      potential may share morphological characters typical for endangered C. carassius
      highlights a need to combine genetic investigations of Carassius cryptic
      diversity with conservation measures of C. carassius in Europe.

PMID- 29360832
TI  - Evaluation of the short form of "Experience in Close Relationships" (Revised,
      German Version "ECR-RD12") - A tool to measure adult attachment in primary care.
AB  - Attachment theory helps us to understand patients' health behavior. Attachment
      styles might explain patient differences in coping behavior, self-treatment, or
      patient-provider relationships. In primary care time constrains are relevant. A
      short instrument may facilitate screening and assessment in daily medical
      practice. The aim of this study was to evaluate a 12-item short version of the
      Experience in Close Relationships-revised (ECR-R-D) to be used in primary care
      settings. We included 249 patients from ten general practices in central Germany
      into a cross-sectional study. Exploratory factor analysis was performed to
      evaluate the factor structure of the ECR-items. Cronbach's alpha was used to
      assess internal consistency. The results related to the short form of the ECR are
      in line with those of the German full-length version of the measure (ECR-RD 36).
      Internal consistencies were in an adequate range. The ECR short form can be
      recommended as a screening measure of attachment styles in primary care.

PMID- 29360833
TI  - The role of cGMP as a mediator of lipolysis in bovine oocytes and its effects on
      embryo development and cryopreservation.
AB  - This study aimed to determine the influence of cyclic guanosine 3'5'
      monophosphate (cGMP) and cGMP-dependent kinase (PKG) during in vitro maturation
      (IVM) on lipolysis-related parameters in bovine cumulus-oocyte complexes (COCs),
      and on embryo development and cryosurvival. COCs were matured with cGMP/PKG
      modulators and assessed for metaphase II rates (MII), cGMP levels, lipid content
      in oocytes (OO), transcript abundance for genes involved in lipolysis (ATGL) and
      lipid droplets (PLIN2) in cumulus cells (CC) and OO, and presence of
      phosphorylated (active) hormone sensitive lipase (HSLser563) in OO. Embryo
      development, lipid contents and survival to vitrification were also assessed.
      Phosphodiesterase 5 inhibition (PDE5; cGMP-hydrolyzing enzyme) with 10-5M
      sildenafil (SDF) during 24 h IVM increased cGMP in COCs (56.9 vs 9.5 fMol/COC in
      untreated controls, p<0.05) and did not affect on maturation rate (84.3+/-6.4%
      MII). Fetal calf serum (FCS) in IVM medium decreased cGMP in COCs compared to
      bovine serum albumin (BSA) + SDF (19.6 vs 66.5 fMol/COC, respectively, p<0.05).
      FCS increased lipid content in OO (40.1 FI, p<0.05) compared to BSA (34.6 FI),
      while SDF decreased (29.8 and 29.6 FI, with BSA or FCS, respectively p<0.05). PKG
      inhibitor (KT5823) reversed this effect (38.9 FI, p<0.05). ATGL and PLIN2
      transcripts were detected in CC and OO, but were affected by cGMP and PKG only in
      CC. HSLser563 was detected in OO matured with or without modulators. Reduced
      lipid content in embryos were observed only when SDF was added during IVM and IVC
      (27.6 FI) compared to its use in either or none of the culture periods (34.2 FI,
      p<0.05). Survival to vitrification was unaffected by SDF. In conclusion, cGMP and
      PKG are involved in lipolysis in OO and possibly in CC and embryos; serum
      negatively affects this pathway, contributing to lipid accumulation, and cGMP
      modulation may reduce lipid contents in oocytes and embryos, but without
      improving embryo cryotolerance.

PMID- 29360835
TI  - Correction: Lack of Ecological and Life History Context Can Create the Illusion
      of Social Interactions in Dictyostelium discoideum.
AB  - [This corrects the article DOI: 10.1371/journal.pcbi.1005246.].

PMID- 29360834
TI  - Sex differences in muscle morphology of the knee flexors and knee extensors.
AB  - INTRODUCTION: Females experience higher risk of anterior cruciate ligament (ACL)
      injuries; males experience higher risk of hamstring strain injuries. Differences
      in injury may be partially due to sex differences in knee flexor (KF) to knee
      extensor (KE) muscle size ratio and the proportional size of constituent muscles.
      PURPOSE: To compare the absolute and proportional size, and mass distribution, of
      individual KE and KF muscles, as well as overall size and balance (size ratio) of
      these muscle groups between the sexes. METHODS: T1-weighted axial plane MR images
      (1.5T) of healthy untrained young males and females (32 vs 34) were acquired to
      determine thigh muscle anatomical cross-sectional area (ACSA). Maximal ACSA
      (ACSAmax) of constituent muscles, summated for KF and KE muscle groups, and the
      KF:KE ratio were calculated. RESULTS: Females had 25.3% smaller KE ACSAmax
      (70.9+/-12.1 vs 93.6+/-10.3 cm2; P<0.001) and 29.6% smaller KF ACSAmax than males
      (38.8+/-7.3cm2 vs 55.1+/-7.3cm2; P<0.001). Consequently, females had lower KF:KE
      ACSA ratio (P = 0.031). There were sex differences in the proportional size of
      2/4 KE and 5/6 KF. In females, vastus lateralis (VL), biceps femoris long-head
      (BFlh) and semimembranosus (SM) were a greater proportion and sartorius (SA),
      gracilis (GR) and biceps femoris short-head (BFsh) a smaller proportion of their
      respective muscle groups compared to males (All P<0.05). CONCLUSION: Sex
      differences in KF:KE ACSAmax ratio may contribute to increased risk of ACL injury
      in females. Sex discrepancies in absolute and proportional size of SA, GR, VL and
      BFlh may contribute further anatomical explanations for sex differences in injury
      incidence.

PMID- 29360836
TI  - Well-child care delivery in the community in China: Related factors and quality
      analysis of services.
AB  - Well-child health care services are essential for maintaining optimum child
      health and development. This study's aim was to evaluate the quality of such
      services and identify factors affecting service quality from the perspective of
      well-child health care providers located in China's Hunan Province. To achieve
      this, a qualitative descriptive method was employed, with 22 well-child health
      care providers being recruited, using purposive sampling, from among the
      provinces' government community health centers. The participants completed
      individual semi-structured interviews lasting approximately 25-30 minutes that
      were designed to obtain their views on well-child health care administration in
      the province. Then, the interview transcripts were analyzed thematically. The
      main finding was that participants felt that the delivery of well-child health
      care services in Hunan Province is insufficient. Factors they mentioned as
      negatively affecting the delivery of such services included the region's
      fragmented primary health care system, inadequate attention to this issue from
      parents and community health care center managers, and a lack of specialized well
      child care knowledge. Thus, currently, well-child health care is not being
      successfully implemented in Hunan Province; consequently, in order to
      successfully implement well-child health care in this region, community health
      care centers should invest more resources and funding, particularly into
      education programs for well-child health care providers.

PMID- 29360837
TI  - Modeling specific action potentials in the human atria based on a minimal single
      cell model.
AB  - We present an effective method to model empirical action potentials of specific
      patients in the human atria based on the minimal model of Bueno-Orovio, Cherry
      and Fenton adapted to atrial electrophysiology. In this model, three ionic are
      currents introduced, where each of it is governed by a characteristic time scale.
      By applying a nonlinear optimization procedure, a best combination of the
      respective time scales is determined, which allows one to reproduce specific
      action potentials with a given amplitude, width and shape. Possible applications
      for supporting clinical diagnosis are pointed out.

PMID- 29360838
TI  - Characterization of plasmids harboring blaCTX-M and blaCMY genes in E. coli from
      French broilers.
AB  - Resistance to extended-spectrum cephalosporins (ESC) is a global health issue.
      The aim of this study was to analyze and compare plasmids coding for resistance
      to ESC isolated from 16 avian commensal and 17 avian pathogenic Escherichia coli
      (APEC) strains obtained respectively at slaughterhouse or from diseased broilers
      in 2010-2012. Plasmid DNA was used to transform E. coli DH5alpha, and the
      resistances of the transformants were determined. The sequences of the ESC
      resistance plasmids prepared from transformants were obtained by Illumina (33
      plasmids) or PacBio (1 plasmid). Results showed that 29 of these plasmids
      contained the blaCTX-M-1 gene and belonged to the IncI1/ST3 type, with 27 and 20
      of them carrying the sul2 or tet(A) genes respectively. Despite their diverse
      origins, several plasmids showed very high percentages of identity. None of the
      blaCTX-M-1-containing plasmid contained APEC virulence genes, although some of
      them were detected in the parental strains. Three plasmids had the blaCMY-2 gene,
      but no other resistance gene. They belonged to IncB/O/K/Z-like or IncFIA/FIB
      replicon types. The blaCMY-2 IncFIA/FIB plasmid was obtained from a strain
      isolated from a diseased broiler and also containing a blaCTX-M-1 IncI1/ST3
      plasmid. Importantly APEC virulence genes (sitA-D, iucA-D, iutA, hlyF, ompT, etsA
      C, iss, iroB-E, iroN, cvaA-C and cvi) were detected on the blaCMY-2 plasmid. In
      conclusion, our results show the dominance and high similarity of blaCTX-M-1
      IncI1/ST3 plasmids, and the worrying presence of APEC virulence genes on a blaCMY
      2 plasmid.

PMID- 29360839
TI  - Comments on species divergence in the genus Sphaerium (Bivalvia) and phylogenetic
      affinities of Sphaerium nucleus and S. corneum var. mamillanum based on
      karyotypes and sequences of 16S and ITS1 rDNA.
AB  - Chromosome, 16S and ITS1 rDNA sequence analyses were used to obtain reliable
      diagnostic characters and to clarify phylogenetic relationships of sphaeriid
      bivalves of the genus Sphaerium. The species studied were found to be diploid,
      with modal number 2n = 28 in S. nucleus and 2n = 30 in S. corneum var.
      mamillanum. Small, biarmed, C- negative B chromosomes were found in all studied
      populations of both species. Karyological and molecular markers revealed no
      differences between S. corneum s. str. and S. corneum var. mamillanum. No
      intraspecific differences were found in the basic karyotype of S. nucleus.
      Molecular analyses, however, uncovered three genetically distinct ITS1 lineages:
      one comprised of samples from Lithuania, Slovakia, and Russia, another from
      Czech, and a third from Ukraine. Additionally to known 16S haplotype from
      Ukraine, three new 16S haplotypes of S. nucleus were detected: one in the samples
      from Lithuania and Russia, one in Slovakian and one in Czech population. In the
      ITS1 phylogenetic tree, all branches of S. nucleus clustered in one clade. In the
      16S phylogenetic tree, however, the haplotype of Czech S. nucleus formed a
      separate branch, distant from three other haplotypes of S. nucleus. Molecular
      results indicate that in the context of the Evolutionary Species Concept the S.
      nucleus morphospecies may represent a complex of separate taxa, however referring
      on the Biological Species Concept the genetic lineages could represent the
      intraspecific variability.

PMID- 29360840
TI  - Robot-assisted laparoscopic surgery versus conventional laparoscopic surgery in
      randomized controlled trials: A systematic review and meta-analysis.
AB  - IMPORTANCE: This review provides a comprehensive comparison of treatment outcomes
      between robot-assisted laparoscopic surgery (RLS) and conventional laparoscopic
      surgery (CLS) based on randomly-controlled trials (RCTs). OBJECTIVES: We employed
      RCTs to provide a systematic review that will enable the relevant community to
      weigh the effectiveness and efficacy of surgical robotics in controversial fields
      on surgical procedures both overall and on each individual surgical procedure.
      EVIDENCE REVIEW: A search was conducted for RCTs in PubMed, EMBASE, and Cochrane
      databases from 1981 to 2016. Among a total of 1,517 articles, 27 clinical reports
      with a mean sample size of 65 patients per report (32.7 patients who underwent
      RLS and 32.5 who underwent CLS), met the inclusion criteria. FINDINGS: CLS shows
      significant advantages in total operative time, net operative time, total
      complication rate, and operative cost (p < 0.05 in all cases), whereas the
      estimated blood loss was less in RLS (p < 0.05). As subgroup analyses, conversion
      rate on colectomy and length of hospital stay on hysterectomy statistically
      favors RLS (p < 0.05). CONCLUSIONS: Despite higher operative cost, RLS does not
      result in statistically better treatment outcomes, with the exception of lower
      estimated blood loss. Operative time and total complication rate are
      significantly more favorable with CLS.

PMID- 29360841
TI  - Does directly administered antiretroviral therapy represent good value for money
      in sub-Saharan Africa? A cost-utility and value of information analysis.
AB  - BACKGROUND: Successful antiretroviral therapy (ART) relies on the optimal level
      of ART adherence to achieve reliable viral suppression, avert HIV drug
      resistance, and prevent avoidable deaths. It has been shown that there are
      various groups of people living with HIV at high-risk of non-adherence to ART in
      sub-Saharan Africa. The objective of this study was to examine the cost
      effectiveness and value-of-information of directly administered antiretroviral
      therapy (DAART) versus self-administered ART among people living with HIV, at
      high risk of non-adherence to ART in sub-Saharan Africa. METHODS AND FINDINGS: A
      Markov model was developed that describes the transition between HIV stages based
      on the CD4 count, along with direct costs, quality of life and the mortality rate
      associated with DAART in comparison with self-administered ART. Data used in the
      model were derived from the published literature. A health system perspective was
      employed using a life-time time horizon. Probabilistic sensitivity analysis was
      performed to determine the impact of parameter uncertainty. Value of information
      analysis was also conducted. The expected cost of self-administered ART and DAART
      were $5,200 and $15,500 and the expected QALYs gained were 8.52 and 9.75
      respectively, giving an incremental cost effectiveness ratio of $8,400 per QALY
      gained. The analysis demonstrated that the annual cost DAART needs to be priced
      below $200 per patient to be cost-effective. The probability that DAART was cost
      effective was 1% for a willingness to pay threshold of $5,096 for sub-Saharan
      Africa. The value of information associated with the cost of DAART and its
      effectiveness was substantial. CONCLUSIONS: From the perspective of the health
      care payer in sub-Saharan Africa, DAART cannot be regarded as cost-effective
      based on current information. The value of information analysis showed that
      further research will be worthwhile and potentially cost-effective in resolving
      the uncertainty about whether or not to adopt DAART.

PMID- 29360843
TI  - Steady state visual evoked potential (SSVEP) based brain-computer interface (BCI)
      performance under different perturbations.
AB  - Brain-computer interface (BCI) paradigms are usually tested when environmental
      and biological artifacts are intentionally avoided. In this study, we
      deliberately introduced different perturbations in order to test the robustness
      of a steady state visual evoked potential (SSVEP) based BCI. Specifically we
      investigated to what extent a drop in performance is related to the degraded
      quality of EEG signals or rather due to increased cognitive load. In the online
      tasks, subjects focused on one of the four circles and gave feedback on the
      correctness of the classification under four conditions randomized across
      subjects: Control (no perturbation), Speaking (counting loudly and repeatedly
      from one to ten), Thinking (mentally counting repeatedly from one to ten), and
      Listening (listening to verbal counting from one to ten). Decision tree, Naive
      Bayes and K-Nearest Neighbor classifiers were used to evaluate the classification
      performance using features generated by canonical correlation analysis. During
      the online condition, Speaking and Thinking decreased moderately the mean
      classification accuracy compared to Control condition whereas there was no
      significant difference between Listening and Control conditions across subjects.
      The performances were sensitive to the classification method and to the
      perturbation conditions. We have not observed significant artifacts in EEG during
      perturbations in the frequency range of interest except in theta band. Therefore
      we concluded that the drop in the performance is likely to have a cognitive
      origin. During the Listening condition relative alpha power in a broad area
      including central and temporal regions primarily over the left hemisphere
      correlated negatively with the performance thus most likely indicating active
      suppression of the distracting presentation of the playback. This is the first
      study that systematically evaluates the effects of natural artifacts (i.e.
      mental, verbal and audio perturbations) on SSVEP-based BCIs. The results can be
      used to improve individual classification performance taking into account effects
      of perturbations.

PMID- 29360842
TI  - A comparative transcriptome analysis of a wild purple potato and its red mutant
      provides insight into the mechanism of anthocyanin transformation.
AB  - In this study, a red mutant was obtained through in vitro regeneration of a wild
      purple potato. High-performance liquid chromatography and Mass spectrometry
      analysis revealed that pelargonidin-3-O-glucoside and petunidin-3-O-glucoside
      were main anthocyanins in the mutant and wild type tubers, respectively. In order
      to thoroughly understand the mechanism of anthocyanin transformation in two
      materials, a comparative transcriptome analysis of the mutant and wild type was
      carried out through high-throughput RNA sequencing, and 295 differentially
      expressed genes (DEGs) were obtained. Real-time qRT-PCR validation of DEGs was
      consistent with the transcriptome date. The DEGs mainly influenced biological and
      metabolic pathways, including phenylpropanoid biosynthesis and translation, and
      biosynthesis of flavone and flavonol. In anthocyanin biosynthetic pathway, the
      analysis of structural genes expressions showed that three genes, one encoding
      phenylalanine ammonia-lyase, one encoding 4-coumarate-CoA ligase and one encoding
      flavonoid 3',5'-hydroxylasem were significantly down-regulated in the mutant; one
      gene encoding phenylalanine ammonia-lyase was significantly up-regulated.
      Moreover, the transcription factors, such as bZIP family, MYB family, LOB family,
      MADS family, zf-HD family and C2H2 family, were significantly regulated in
      anthocyanin transformation. Response proteins of hormone, such as gibberellin,
      abscisic acid and brassinosteroid, were also significantly regulated in
      anthocyanin transformation. The information contributes to discovering the
      candidate genes in anthocyanin transformation, which can serve as a comprehensive
      resource for molecular mechanism research of anthocyanin transformation in
      potatoes.

PMID- 29360844
TI  - Mid-term sustained relief from headaches after balloon angioplasty of the
      internal jugular veins in patients with multiple sclerosis.
AB  - OBJECTIVES: Multiple sclerosis (MS) patients frequently suffer from headaches and
      fatigue, and many reports have linked headaches with intracranial and/or
      extracranial venous obstruction. We therefore designed a study involving MS
      patients diagnosed with obstructive disease of internal jugular veins (IJVs),
      with the aim of evaluating the impact of percutaneous transluminal angioplasty
      (PTA) on headache and fatigue indicators. METHODS: 286 MS patients (175 relapsing
      remitting (RR), 75 secondary progressive (SP), and 36 primary progressive (PP)),
      diagnosed with obstructive disease of IJVs, underwent PTA of IJVs during the
      period 2011-2015. This included 113 headache positive patients (82 RR, 22 SP, and
      9 PP) and 277 fatigue positive patients (167 RR, 74 SP, and 36 PP). Migraine
      Disability Assessment (MIDAS), and the Fatigue Severity Scale (FSS) were
      evaluated: before PTA; 3-months after PTA; and at final follow-up in 2017.
      Patients were evaluated with Doppler sonography of the IJVs at 1, 6 and 12 months
      after PTA and yearly thereafter. Non-parametric statistical analysis was
      performed using a combination of the Friedman test and Spearman correlation
      analysis. RESULTS: With the exception of the PP patients there were significant
      reductions (all p < 0.001) in the MIDAS and FSS scores in the 3-month following
      PTA. The improvement in MIDAS score following PTA was maintained throughout the
      follow-up period in both the RR (p < 0.001; mean of 3.55 years) and SP (p =
      0.002; mean of 3.52 years) MS cohorts. With FSS, significant improvement was only
      observed at 2017 follow-up in the RR patients (p < 0.001; mean of 3.37 years). In
      the headache-positive patients, post-PTA MIDAS score was significantly negatively
      correlated with the change in the blood flow score in the left (r = -0.238, p =
      0.031) and right (r = -0.250, p = 0.023) IJVs in the RR patients and left IJV (r
      = -0.727, p = 0.026) in the PP patients. In the fatigue-positive cohort, post-PTA
      FSS score was also significantly negatively correlated with the change in blood
      flow in the right IJV in the PP patients (r = -0.423, p = 0.010). In addition,
      the pre and post-PTA FSS scores were significantly positively correlated in the
      fatigue-positive RR (r = 0.249, p = 0.001) and SP patients (r = 0.272, p =
      0.019). CONCLUSIONS: The intervention of PTA was associated with a large and
      sustained (>3 years) reduction in MIDAS score in both RR and SP MS patients.
      While a similar initial post-PTA reduction in FSS score was also observed, this
      was not maintained in the SP and PP patients, although it remained significant at
      follow-up (>3 years) in the RR MS patients. This suggests that venoplasty might
      be a useful intervention for treating patients with persistent headaches and
      selected concomitant obstructive disease of the IJVs.

PMID- 29360845
TI  - Non-vitamin K antagonist oral anticoagulants versus warfarin for the prevention
      of spontaneous echo-contrast and thrombus in patients with atrial fibrillation or
      flutter undergoing cardioversion: A trans-esophageal echocardiography study.
AB  - Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal
      echocardiography (TEE) is known as a strong surrogate marker for future risk of
      ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter
      (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC)
      compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is
      currently unknown. AF or AFL patients who underwent direct current cardioversion
      (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single
      center were analyzed. The prevalence of SEC and thrombus were compared between
      patients who received NOAC and those who took warfarin. NOAC included direct
      thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were
      considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent
      TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days
      were excluded. Finally, 344 patients were included for the analysis (180 warfarin
      users vs. 164 NOAC users). No significant difference in the prevalence of SEC
      (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus
      (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC
      group. In multivariate analysis, there was no association between NOAC and risk
      of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796-2.297, p = 0.265) or thrombus (OR:
      3.4, 95% CI: 0.726-16.039, p = 0.120). In conclusion, effectiveness of NOAC is
      comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL
      undergoing DCCV. However, numerical increase in the prevalence of thrombus in
      NOAC group warrants further evaluation.

PMID- 29360846
TI  - The activation of G protein-coupled estrogen receptor induces relaxation via cAMP
      as well as potentiates contraction via EGFR transactivation in porcine coronary
      arteries.
AB  - Estrogen exerts protective effects against cardiovascular diseases in
      premenopausal women, but is associated with an increased risk of both coronary
      heart disease and stroke in older postmenopausal women. Studies have shown that
      activation of the G-protein-coupled estrogen receptor 1 (GPER) can cause either
      relaxation or contraction of arteries. It is highly likely that these dual
      actions of GPER may contribute to the seemingly paradoxical effects of estrogen
      in regulating coronary artery function. The objective of this study was to test
      the hypothesis that activation of GPER enhances agonist-stimulated porcine
      coronary artery contraction via epidermal growth factor receptor (EGFR)
      transactivation and its downstream extracellular signal-regulated kinases
      (ERK1/2) pathway. Isometric tension studies and western blot were performed to
      determine the effect of GPER activation on coronary artery contraction. Our
      findings demonstrated that G-1 caused concentration-dependent relaxation of ET-1
      induced contraction, while pretreatment of arterial rings with G-1 significantly
      enhanced ET-1-induced contraction. GPER antagonist, G-36, significantly inhibited
      both the G-1-induced relaxation effect and G-1-enhanced ET-1 contraction.
      Gallein, a Gbetagamma inhibitor, significantly increased G-1-induced relaxation,
      yet inhibited G-1-enhanced ET-1-mediated contraction. Similarly, inhibition of
      EGFR with AG1478 or inhibition of Src with phosphatase 2 further increased G-1
      induced relaxation responses in coronary arteries, but decreased G-1-enhanced ET
      1-induced contraction. Western blot experiments in porcine coronary artery smooth
      muscle cells (PCASMC) showed that G-1 increased tyrosine phosphorylation of EGFR,
      which was inhibited by AG-1478. Furthermore, enzyme-linked immunosorbent assays
      showed that the level of heparin-binding EGF (HB-EGF) released by ET-1 treatment
      increased two-fold; whereas pre-incubation with G-1 further increased ET-1
      induced HB-EGF release to four-fold over control conditions. Lastly, the role of
      ERK1/2 was determined by applying the MEK inhibitor, PD98059, in isometric
      tension studies and detecting phospho-ERK1/2 in immunoblotting. PD98059
      potentiated G-1-induced relaxation response, but blocked G-1-enhanced ET-1
      induced contraction. By western blot, G-1 treatment decreased phospho-ERK1/2,
      however, in the presence of the adenylyl cyclase inhibitor, SQ22536, G-1
      significantly increased ERK1/2 phosphorylation in PCASMC. These data demonstrate
      that activation of GPER induces relaxation via cAMP as well as contraction via a
      mechanism involving transactivation of EGFR and the phosphorylation of ERK1/2 in
      porcine coronary arteries.

PMID- 29360847
TI  - Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic
      fibrosis airway epithelial cells.
AB  - BACKGROUND: Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene
      can reduce function of the CFTR ion channel activity and impair cellular chloride
      secretion. The gold standard method to assess CFTR function of ion transport
      using the Ussing chamber requires a high number of airway epithelial cells grown
      at air-liquid interface, limiting the application of this method for high
      throughput screening of potential therapeutic compounds in primary airway
      epithelial cells (pAECs) featuring less common CFTR mutations. This study
      assessed an alternative approach, using a small scale halide assay that can be
      adapted for a personalized high throughput setting to analyze CFTR function of
      pAEC. METHODS: Pediatric pAECs derived from children with CF (pAECCF) were
      established and expanded as monolayer cultures, before seeding into 96-well
      plates for the halide assay. Cells were then transduced with an adenoviral
      construct containing yellow fluorescent protein (eYFP) reporter gene, alone or in
      combination with either wild-type CFTR (WT-CFTR) or p.Phe508del CFTR. Four days
      post transduction, cells were stimulated with forskolin and genistein, and
      assessed for quenching of the eYFP signal following injection of iodide solution
      into the assay media. RESULTS: Data showed that pAECCF can express eYFP at high
      efficiency following transduction with the eYFP construct. The halide assay was
      able to discriminate functional restoration of CFTR in pAECCF treated with either
      WT-CFTR construct or the positive controls syntaxin 8 and B-cell receptor
      associated protein 31 shRNAs. SIGNIFICANCE: The current study demonstrates that
      the halide assay can be adapted for pediatric pAECCF to evaluate restoration of
      CFTR function. With the ongoing development of small molecules to modulate the
      folding and/or activity of various mutated CFTR proteins, this halide assay
      presents a small-scale personalized screening platform that could assess
      therapeutic potential of molecules across a broad range of CFTR mutations.

PMID- 29360848
TI  - Growth performance, organ-level ionic relations and organic osmoregulation of
      Elaeagnus angustifolia in response to salt stress.
AB  - Elaeagnus angustifolia is one of the most extensively afforested tree species in
      environment-harsh regions of northern China. Despite its exceptional tolerance to
      saline soil, the intrinsic adaptive physiology has not been revealed. In this
      study, we investigated the growth, organ-level ionic relations and organic
      osmoregulation of the seedlings hydroponically treated with 0, 100 and 200 mM
      NaCl for 30 days. We found that the growth characteristics and the whole-plant
      dry weight were not obviously stunted, but instead, were even slightly stimulated
      by the treatment of 100 mM NaCl. In contrast, these traits were significantly
      inhibited by 200 mM NaCl treatment. Interestingly, as compared with the control
      (0 mM NaCl), both 100 and 200 mM NaCl treatments had a promotional effect on root
      growth as evidenced by 26.3% and 2.4% increases in root dry weight, respectively.
      Roots had the highest Na+ and Cl- concentrations and obviously served as the sink
      for the net increased Na+ and Cl-, while, stems might maintain the capacity of
      effective Na+ constraint, resulting in reduced Na+ transport to the leaves. K+,
      Ca2+ and Mg2+ concentrations in three plant organs of NaCl-treated seedlings
      presented a substantial decline, eventually leading to an enormously drop of
      K+/Na+ ratio. As the salt concentration increased, proline and soluble protein
      contents continuously exhibited a prominent and a relatively tardy accumulation,
      respectively, whereas soluble sugar firstly fell to a significant level and then
      regained to a level that is close to that of the control. Taken together, our
      results provided quantitative measures that revealed some robust adaptive
      physiological mechanisms underpinning E. angustifolia's moderately high salt
      tolerance, and those mechanisms comprise scalable capacity for root Na+ and Cl-
      storage, effectively constrained transportation of Na+ from stems to leaves, root
      compensatory growth, as well as an immediate and prominent leaf proline
      accumulation.

PMID- 29360849
TI  - High contributions of sea ice derived carbon in polar bear (Ursus maritimus)
      tissue.
AB  - Polar bears (Ursus maritimus) rely upon Arctic sea ice as a physical habitat.
      Consequently, conservation assessments of polar bears identify the ongoing
      reduction in sea ice to represent a significant threat to their survival.
      However, the additional role of sea ice as a potential, indirect, source of
      energy to bears has been overlooked. Here we used the highly branched isoprenoid
      lipid biomarker-based index (H-Print) approach in combination with quantitative
      fatty acid signature analysis to show that sympagic (sea ice-associated), rather
      than pelagic, carbon contributions dominated the marine component of polar bear
      diet (72-100%; 99% CI, n = 55), irrespective of differences in diet composition.
      The lowest mean estimates of sympagic carbon were found in Baffin Bay bears,
      which were also exposed to the most rapidly increasing open water season.
      Therefore, our data illustrate that for future Arctic ecosystems that are likely
      to be characterised by reduced sea ice cover, polar bears will not only be
      impacted by a change in their physical habitat, but also potentially in the
      supply of energy to the ecosystems upon which they depend. This data represents
      the first quantifiable baseline that is critical for the assessment of likely
      ongoing changes in energy supply to Arctic predators as we move into an
      increasingly uncertain future for polar ecosystems.

PMID- 29360850
TI  - A prospective study of frequency of eating restaurant prepared meals and
      subsequent 9-year risk of all-cause and cardiometabolic mortality in US adults.
AB  - Restaurant prepared foods are known to be energy-dense and high in fat and
      sodium, but lower in protective nutrients. There is evidence of higher risk of
      adiposity, type II diabetes, and heart disease in frequent consumers of
      restaurant meals. However, the risk of mortality as a long-term health
      consequence of frequent consumption of restaurant meals has not been examined. We
      examined the prospective risk of all-cause and coronary heart disease,
      cerebrovascular disease and diabetes (cardiometabolic) mortality in relation to
      frequency of eating restaurant prepared meals in a national cohort. We used
      frequency of eating restaurant prepared meals information collected in the
      National Health and Nutrition Examination Surveys, conducted from 1999-2004, with
      mortality follow-up completed through Dec. 31, 2011 (baseline age >= 40y; n =
      9107). We estimated the relative hazard of all-cause and cardiometabolic
      mortality associated with weekly frequency of eating restaurant meals using Cox
      proportional hazards regression methods to adjust for multiple covariates. All
      analyses accounted for complex survey design and included sample weights. Over
      33% of all respondents reported eating >=3 restaurant prepared meals/week. In
      this cohort, 2200 deaths due to all causes and 665 cardiometabolic deaths
      occurred over a median follow-up of 9 years. The covariate-adjusted hazard ratio
      of all cause or cardiometabolic mortality in men and women reporters of <1 or 1-2
      restaurant prepared meals did not differ from those reporting >=3 meals/week
      (P>0.05). The results were robust to effect modification by baseline BMI, years
      of education, and baseline morbidity. Expectedly, the 24-h dietary intakes of
      whole grains, fruits, dietary fiber, folate, vitamin C, potassium and magnesium
      at baseline were lower, but energy, energy density, and energy from fat were
      higher in more frequent restaurant meal reporters (P<0.05). Baseline serum HDL
      cholesterol, folate, and some carotenoids were inversely associated with the
      frequency of eating restaurant prepared meals (P<0.05); however, serum
      concentrations of total cholesterol, triglycerides, fasting glucose, insulin,
      glycated hemoglobin, and c-reactive protein were unrelated (P<0.05). The weekly
      frequency of eating restaurant prepared meals and prospective risk of mortality
      after 9 years were not related in this cohort.

PMID- 29360851
TI  - Left atrial concomitant surgical ablation for treatment of atrial fibrillation in
      cardiac surgery: A meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: Surgical ablation is a generally established treatment for patients
      with atrial fibrillation undergoing concomitant cardiac surgery. Left atrial (LA)
      lesion set for ablation is a simplified procedure suggested to reduce the surgery
      time and morbidity after procedure. The present meta-analysis aims to explore the
      outcomes of left atrial lesion set versus no ablative treatment in patients with
      AF undergoing cardiac surgery. METHODS: A literature research was performed in
      six database from their inception to July 2017, identifying all relevant
      randomized controlled trials (RCTs) comparing left atrial lesion set versus no
      ablative treatment in AF patient undergoing cardiac surgery. Data were extracted
      and analyzed according to predefined clinical endpoints. RESULTS: Eleven relevant
      RCTs were included for analysis in the present study. The prevalence of sinus
      rhythm in ablation group was significantly higher at discharge, 6-month and 1
      year follow-up period. The morbidity including 30 day mortality, late all-cause
      mortality, reoperation for bleeding, permanent pacemaker implantation and
      neurological events were of no significant difference between two groups.
      CONCLUSIONS: The result of our meta-analysis demonstrates that left atrial lesion
      set is an effective and safe surgical ablation strategy for AF patients
      undergoing concomitant cardiac surgery.

PMID- 29360852
TI  - Convergence of miR-143 overexpression, oxidative stress and cell death in HCT116
      human colon cancer cells.
AB  - MicroRNAs (miRNAs) regulate a wide variety of biological processes, including
      tumourigenesis. Altered miRNA expression is associated with deregulation of
      signalling pathways, which in turn cause abnormal cell growth and de
      differentiation, contributing to cancer. miR-143 and miR-145 are anti
      tumourigenic and influence the sensitivity of tumour cells to chemotherapy and
      targeted therapy. Comparative proteomic analysis was performed in HCT116 human
      colon cancer cells stably transduced with miR-143 or miR-145. Immunoblotting
      analysis validated the proteomic data in stable and transient miRNA
      overexpression conditions in human colon cancer cells. We show that approximately
      100 proteins are differentially expressed in HCT116 human colon cancer cells
      stably transduced with miR-143 or miR-145 compared to Empty control cells.
      Further, Gene Ontology and pathway enrichment analysis indicated that proteins
      involved in specific cell signalling pathways such as cell death, response to
      oxidative stress, and protein folding might be modulated by these miRNAs. In
      particular, antioxidant enzyme superoxide dismutase 1 (SOD1) was downregulated by
      stable expression of either miR-143 or miR-145. Further, SOD1 gain-of-function
      experiments rescued cells from miR-143-induced oxidative stress. Moreover, miR
      143 overexpression increased oxaliplatin-induced apoptosis associated with
      reactive oxygen species generation, which was abrogated by genetic and
      pharmacological inhibition of oxidative stress. Overall, miR-143 might circumvent
      resistance of colon cancer cells to oxaliplatin via increased oxidative stress in
      HCT116 human colon cancer cells.

PMID- 29360853
TI  - Effects of short-term warming and nitrogen addition on the quantity and quality
      of dissolved organic matter in a subtropical Cunninghamia lanceolata plantation.
AB  - Increasing temperature and nitrogen (N) deposition are two large-scale changes
      projected to occur over the coming decades. The effects of these changes on
      dissolved organic matter (DOM) are largely unknown. This study aimed to assess
      the effects of warming and N addition on the quantity and quality of DOM from a
      subtropical Cunninghamia lanceolata plantation. Between 2014 and 2016, soil
      solutions were collected from 0-15, 15-30, and 30-60 cm depths by using a
      negative pressure sampling method. The quantity and quality of DOM were measured
      under six different treatments. The spectra showed that the DOM of the forest
      soil solution mainly consisted of aromatic protein-like components, microbial
      degradation products, and negligible amounts of humic-like substances. Warming, N
      addition, and warming + N addition significantly inhibited the concentration of
      dissolved organic carbon (DOC) in the surface (0-15 cm) soil solution. Our
      results suggested that warming reduced the amount of DOM originating from
      microbes. The decrease in protein and carboxylic acid contents was mostly
      attributed to the reduction of DOC following N addition. The warming + N addition
      treatment showed an interactive effect rather than an additive effect. Thus,
      short-term warming and warming + N addition decreased the quantity of DOM and
      facilitated the migration of nutrients to deeper soils. Further, N addition
      increased the complexity of the DOM structure. Hence, the loss of soil nutrients
      and the rational application of N need to be considered in order to prevent the
      accumulation of N compounds in soil.

PMID- 29360854
TI  - Diagnostic efficacy of smear cytology and Robinson's cytological grading of
      canine mammary tumors with respect to histopathology, cytomorphometry, metastases
      and overall survival.
AB  - Cytology is a simple, rapid, and inexpensive method used for pre-operative
      diagnosis of canine mammary tumors (CMTs) in veterinary practice. Studies related
      to human breast cancer showed the Robinson's grading system-established for
      invasive ductal carcinoma, not otherwise specified (IDC, NOS) and used on
      cytological material-to not only closely correspond to the histopathological
      grading but also be helpful in assessing prognosis and selecting most suitable
      treatments before surgery. The objectives of this study were: to evaluate the
      accuracy of cytological diagnosis and cytological Robinson's grading system
      compared to the histopathological examination of CMTs; to compare of cytological
      features and cytomorphometric parameters with tumor behavior, as well as
      cytological and histological grading; and to determine an association of the
      Robinson's grading system and cytological background details with metastases, and
      patients' survival. We report substantial diagnostic accuracy in detecting simple
      types and high grade tumors. Cytological diagnosis of tumor behavior showed
      relatively low sensitivity and specificity compared to human studies, and this
      might be caused by the heterogeneous morphology of CMTs. The presence of
      mucosecretory material and extracellular matrix was not significantly associated
      with tumor behavior. We report a positive correlation between both grading
      systems and cytological features (included in Robinson's grading), the presence
      of necrotic debris, inflammation, and red blood cells. A negative correlation was
      determined only for the presence of extracellular matrix. The univariate and
      multivariate analyses confirmed a significantly higher risk of developing
      metastasis and shorter overall survival for dogs with tumors of grade 2 or 3 on
      cytology. In addition, these tumors were the most common cause of CMT-related
      deaths in dogs. Taken together, our findings suggest that the Robinson's method
      of cytological grading applied for malignant CMTs evaluated in cytological smears
      regardless of tumor type can be adapted to veterinary cytology. Additionally,
      some background features seem to aid malignancy assessment.

PMID- 29360855
TI  - Identification and analysis of OsttaDSP, a phosphoglucan phosphatase from
      Ostreococcus tauri.
AB  - Ostreococcus tauri, the smallest free-living (non-symbiotic) eukaryote yet
      described, is a unicellular green alga of the Prasinophyceae family. It has a
      very simple cellular organization and presents a unique starch granule and
      chloroplast. However, its starch metabolism exhibits a complexity comparable to
      higher plants, with multiple enzyme forms for each metabolic reaction. Glucan
      phosphatases, a family of enzymes functionally conserved in animals and plants,
      are essential for normal starch or glycogen degradation in plants and mammals,
      respectively. Despite the importance of O. tauri microalgae in evolution, there
      is no information available concerning the enzymes involved in reversible
      phosphorylation of starch. Here, we report the molecular cloning and heterologous
      expression of the gene coding for a dual specific phosphatase from O. tauri
      (OsttaDSP), homologous to Arabidopsis thaliana LSF2. The recombinant enzyme was
      purified to electrophoretic homogeneity to characterize its oligomeric and
      kinetic properties accurately. OsttaDSP is a homodimer of 54.5 kDa that binds and
      dephosphorylates amylopectin. Also, we also determined that residue C162 is
      involved in catalysis and possibly also in structural stability of the enzyme.
      Our results could contribute to better understand the role of glucan phosphatases
      in the metabolism of starch in green algae.

PMID- 29360857
TI  - Using geomorphological variables to predict the spatial distribution of plant
      species in agricultural drainage networks.
AB  - To optimize ecosystem services provided by agricultural drainage networks
      (ditches) in headwater catchments, we need to manage the spatial distribution of
      plant species living in these networks. Geomorphological variables have been
      shown to be important predictors of plant distribution in other ecosystems
      because they control the water regime, the sediment deposition rates and the sun
      exposure in the ditches. Whether such variables may be used to predict plant
      distribution in agricultural drainage networks is unknown. We collected presence
      and absence data for 10 herbaceous plant species in a subset of a network of
      drainage ditches (35 km long) within a Mediterranean agricultural catchment. We
      simulated their spatial distribution with GLM and Maxent model using
      geomorphological variables and distance to natural lands and roads. Models were
      validated using k-fold cross-validation. We then compared the mean Area Under the
      Curve (AUC) values obtained for each model and other metrics issued from the
      confusion matrices between observed and predicted variables. Based on the results
      of all metrics, the models were efficient at predicting the distribution of seven
      species out of ten, confirming the relevance of geomorphological variables and
      distance to natural lands and roads to explain the occurrence of plant species in
      this Mediterranean catchment. In particular, the importance of the landscape
      geomorphological variables, ie the importance of the geomorphological features
      encompassing a broad environment around the ditch, has been highlighted. This
      suggests that agro-ecological measures for managing ecosystem services provided
      by ditch plants should focus on the control of the hydrological and
      sedimentological connectivity at the catchment scale. For example, the density of
      the ditch network could be modified or the spatial distribution of vegetative
      filter strips used for sediment trapping could be optimized. In addition, the
      vegetative filter strips could constitute new seed bank sources for species that
      are affected by the distance to natural lands and roads.

PMID- 29360856
TI  - Midgut transcriptomal response of the rice leaffolder, Cnaphalocrocis medinalis
      (Guenee) to Cry1C toxin.
AB  - Cnaphalocrocis medinalis (Guenee) is one of the important insect pests in rice
      field. Bt agents were recommended in the C. medinalis control and Bt rice is bred
      as a tactic to control this insect. However, the tolerance or resistance of
      insect to Bt protein is a main threat to the application of Bt protein. In order
      to investigate the response of C. medinalis transcriptome in defending a Cry1C
      toxin, high-through RNA-sequencing was carried in the C. medinalis larvae treated
      with and without Cry1C toxin. A total of 35,586 high-quality unigenes was
      annotated in the transcriptome of C. medinalis midgut. The comparative analysis
      identified 6,966 differently expressed unigenes (DEGs) between the two
      treatments. GO analysis showed that these genes involved in proteolysis and
      extracellular region. Among these DEGs, carboxylesterase, glutathione S
      transferase and P450 were differently expressed in the treated C. medinalis
      midgut. Furthermore, trypsin, chymotrypsin, and carboxypeptidase were identified
      in DEGs, and most of them up-regulated. In addition, thirteen ABC transporters
      were downregulated and three upregulated in Cry1C-treated C. medinalis midgut.
      Based on the pathway analysis, antigen processing and presentation pathway, and
      chronic myeloid leukemia pathway were significant in C. medinalis treated with
      Cry1C toxin. These results indicated that serine protease, detoxification enzymes
      and ABC transporter, antigen processing and presentation pathway, and chronic
      myeloid leukemia pathway may involved in the response of C. medinalis to Cry1C
      toxin. This study provides a transcriptomal foundation for the identification and
      functional characterization of genes involved in the toxicity of Bt Cry protein
      against C. medinalis, and provides potential clues to the studies on the
      tolerance or resistance of an agriculturally important insect pest C. medinalis
      to Cry1C toxin.

PMID- 29360858
TI  - Immunostimulatory activity of water-extractable polysaccharides from Cistanche
      deserticola as a plant adjuvant in vitro and in vivo.
AB  - A safe and effective vaccine adjuvant is important in modern vaccines. Various
      Chinese herbal polysaccharides can activate the immune system. Cistanche
      deserticola (CD) is a traditional Chinese herb and an adjuvant candidate. Here,
      we confirmed that water-extractable polysaccharides of CD (WPCD) could modulate
      immune responses in vitro and in vivo. In a dose-dependent manner, WPCD
      significantly promoted the maturation and function of murine marrow-derived
      dendritic cells (BM-DCs) through up-regulating the expression levels of MHC-II,
      CD86, CD80, and CD40, allogenic T cell proliferation, and the yields of IL-12 and
      TNF-alpha via toll-like receptor4 (TLR4), as indicated by in vitro experiments.
      In addition, its immunomodulatory activity was also observed in mice. WPCD
      effectively improved the titers of IgG, IgG1 and IgG2a and markedly enhanced the
      proliferation of T and B cells, the production of IFN-gamma and IL-4 in CD4+ T
      cells and the expression level of IFN-gamma in CD8+ T cells better than Alum.
      Furthermore, WPCD could markedly up-regulate the expression levels of CD40 and
      CD80 on DCs in spleen and down-regulate the Treg frequency. The study suggests
      that polysaccharides of Cistanche deserticola are a safe and effective vaccine
      adjuvant for eliciting both humoral immunity and cellular immunity by activating
      DCs via TLR4 signaling pathway.

PMID- 29360859
TI  - A kinetic investigation of interacting, stimulated T cells identifies conditions
      for rapid functional enhancement, minimal phenotype differentiation, and improved
      adoptive cell transfer tumor eradication.
AB  - For adoptive cell transfer (ACT) immunotherapy of tumor-reactive T cells, an
      effective therapeutic outcome depends upon cell dose, cell expansion in vivo
      through a minimally differentiated phenotype, long term persistence, and strong
      cytolytic effector function. An incomplete understanding of the biological
      coupling between T cell expansion, differentiation, and response to stimulation
      hinders the co-optimization of these factors. We report on a biophysical
      investigation of how the short-term kinetics of T cell functional activation,
      through molecular stimulation and cell-cell interactions, competes with phenotype
      differentiation. T cells receive molecular stimulation for a few minutes to a few
      hours in bulk culture. Following this priming period, the cells are then analyzed
      at the transcriptional level, or isolated as single cells, with continuing
      molecular stimulation, within microchambers for analysis via 11-plex secreted
      protein assays. We resolve a rapid feedback mechanism, promoted by T cell-T cell
      contact interactions, which strongly amplifies T cell functional performance
      while yielding only minimal phenotype differentiation. When tested in mouse
      models of ACT, optimally primed T cells lead to complete tumor eradication. A
      similar kinetic process is identified in CD8+ and CD4+ T cells collected from a
      patient with metastatic melanoma.

PMID- 29360860
TI  - Acute Smc5/6 depletion reveals its primary role in rDNA replication by
      restraining recombination at fork pausing sites.
AB  - Smc5/6, a member of the conserved SMC family of complexes, is essential for
      growth in most organisms. Its exact functions in a mitotic cell cycle are
      controversial, as chronic Smc5/6 loss-of-function alleles produce varying
      phenotypes. To circumvent this issue, we acutely depleted Smc5/6 in budding yeast
      and determined the first cell cycle consequences of Smc5/6 removal. We found a
      striking primary defect in replication of the ribosomal DNA (rDNA) array. Each
      rDNA repeat contains a programmed replication fork barrier (RFB) established by
      the Fob1 protein. Fob1 removal improves rDNA replication in Smc5/6 depleted
      cells, implicating Smc5/6 in the management of programmed fork pausing. A similar
      improvement is achieved by removing the DNA helicase Mph1 whose recombinogenic
      activity can be inhibited by Smc5/6 under DNA damage conditions. DNA 2D gel
      analyses further show that Smc5/6 loss increases recombination structures at RFB
      regions; moreover, mph1? and fob1? similarly reduce this accumulation. These
      findings point to an important mitotic role for Smc5/6 in restraining
      recombination events when protein barriers in rDNA stall replication forks. As
      rDNA maintenance influences multiple essential cellular processes, Smc5/6 likely
      links rDNA stability to overall mitotic growth.

PMID- 29360861
TI  - Genetic diversity of human respiratory syncytial virus circulating among children
      in Ibadan, Nigeria.
AB  - Human respiratory syncytial virus (HRSV) is the most common viral cause of acute
      lower respiratory tract infections (LRTIs) in infants and young children however,
      without an effective vaccine licensed for human use till date. Information on the
      circulating genotypes of HRSV from regions with high-burden of infection is vital
      in the global efforts towards the development of protective vaccine. We report
      here the genotypes of HRSV circulating among children in Ibadan, the first of
      such from Nigeria.Nasopharyngeal and oropharyngeal swabs collected from 231
      children presenting with respiratory infections in some health facilities for
      care as well as those attending immunization centers for routine vaccination in
      Ibadan, Nigeria were used for the study. The 2nd hypervariable (HVR2) region of
      the glycoprotein (G) gene of HRSV was amplified and sequenced using HRSV group
      specific primers. HRSV was detected in 41 out of the 231 samples. Thirty-three of
      the isolates were successfully subtyped(22 subtype A and 11 subtype B). Fourteen
      of the subtype A and all the subtype B were successfully sequenced and genotyped.
      Phylogenetic analysis showed that genotype ON1 with 72 nucleotide (nt)
      duplication was the major subgroup A virus (11 of 14) detected together with
      genotype NA2. All the HRSV subtype B detected belong to the BA genotype with
      characteristic 60nt duplication. The ON1 genotypes vary considerably from the
      prototype strain due to amino acid substitutions including T292I which has not
      been reported elsewhere. The NA2 genotypes have mutations on four antigenic sites
      within the HVR2relative to the prototype A2. In conclusion, three genotypes of
      HRSV were found circulating in Ibadan, Nigeria. Additional study that will
      include isolates from other parts of the country will be done to determine the
      extent of genotype diversity of HRSV circulating in Nigeria.

PMID- 29360862
TI  - Independent associations and effect modification between lifetime substance use
      and recent mood disorder diagnosis with household food insecurity.
AB  - Poor mental health and substance use are associated with food insecurity,
      however, their potential combined effects have not been studied. This study
      explored independent associations and effect modification between lifetime
      substance use and mood disorder in relation to food insecurity. Poisson
      regression analysis of data from British Columbia respondents (n = 13,450; 12
      years+) in the 2007/08 Canadian Community Health Survey was conducted. Measures
      included The Household Food Security Survey Module (7.3% food insecure), recent
      diagnosis of a mood disorder (self-reported; 9.5%), lifetime use of cannabis,
      cocaine/crack, ecstasy, hallucinogens, and speed, any lifetime substance use,
      sociodemographic covariates, and the interaction terms of mood disorder by
      substance. For those with recent diagnosis of a mood disorder the prevalence of
      lifetime substance use ranged between 1.2 to 5.7% and were significantly higher
      than those without recent mood disorder diagnosis or lifetime use of substances
      (p's < 0.05). For respondents with a recent mood disorder diagnosis or who used
      cannabis, food insecurity prevalence was higher compared to the general sample (p
      < 0.001); prevalence was lower for cocaine/crack use (p < 0.05). Significant
      effect modification was found between mood disorder with cannabis, ecstasy,
      hallucinogen and any substance use over the lifetime (PRs 0.51 to 0.64, p's 0.022
      to 0.001). Independent associations were found for cocaine/crack and speed use
      (PRs 1.68, p's < 0.001) and mood disorder (PRs 2.02, p's < 0.001). Based on these
      findings and the existing literature, future study about coping and resilience in
      the context of substance use, mental health, and food insecurity may lead to the
      development of relevant interventions aimed at mental well-being and food
      security.

PMID- 29360863
TI  - Estimating population extinction thresholds with categorical classification trees
      for Louisiana black bears.
AB  - Monitoring vulnerable species is critical for their conservation. Thresholds or
      tipping points are commonly used to indicate when populations become vulnerable
      to extinction and to trigger changes in conservation actions. However,
      quantitative methods to determine such thresholds have not been well explored.
      The Louisiana black bear (Ursus americanus luteolus) was removed from the list of
      threatened and endangered species under the U.S. Endangered Species Act in 2016
      and our objectives were to determine the most appropriate parameters and
      thresholds for monitoring and management action. Capture mark recapture (CMR)
      data from 2006 to 2012 were used to estimate population parameters and variances.
      We used stochastic population simulations and conditional classification trees to
      identify demographic rates for monitoring that would be most indicative of
      heighted extinction risk. We then identified thresholds that would be reliable
      predictors of population viability. Conditional classification trees indicated
      that annual apparent survival rates for adult females averaged over 5 years
      ([Formula: see text]) was the best predictor of population persistence.
      Specifically, population persistence was estimated to be >=95% over 100 years
      when [Formula: see text], suggesting that this statistic can be used as threshold
      to trigger management intervention. Our evaluation produced monitoring protocols
      that reliably predicted population persistence and was cost-effective. We
      conclude that population projections and conditional classification trees can be
      valuable tools for identifying extinction thresholds used in monitoring programs.

PMID- 29360864
TI  - Correction: Aged blood factors decrease cellular responses associated with
      delayed gingival wound repair.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184189.].

PMID- 29360865
TI  - Cathepsin B aggravates coxsackievirus B3-induced myocarditis through activating
      the inflammasome and promoting pyroptosis.
AB  - Cathepsin B (CatB) is a cysteine proteolytic enzyme widely expressed in various
      cells and mainly located in the lysosomes. It contributes to the pathogenesis and
      development of many diseases. However, the role of CatB in viral myocarditis
      (VMC) has never been elucidated. Here we generated the VMC model by
      intraperitoneal injection of coxsackievirus B3 (CVB3) into mice. At day 7 and day
      28, we found CatB was significantly activated in hearts from VMC mice. Compared
      with the wild-type mice receiving equal amount of CVB3, genetic ablation of CatB
      (Ctsb-/-) significantly improved survival, reduced inflammatory cell
      infiltration, decreased serum level of cardiac troponin I, and ameliorated
      cardiac dysfunction, without altering virus titers in hearts. Conversely, genetic
      deletion of cystatin C (Cstc-/-), which markedly enhanced CatB levels in hearts,
      distinctly increased the severity of VMC. Furthermore, compared with the control,
      we found the inflammasome was activated in the hearts of wild-type mice with VMC,
      which was attenuated in the hearts of Ctsb-/- mice but was further enhanced in
      Cstc-/- mice. Consistently, the inflammasome-initiated pyroptosis was reduced in
      Ctsb-/- mice hearts and further increased in Cstc-/- mice. These results suggest
      that CatB aggravates CVB3-induced VMC probably through activating the
      inflammasome and promoting pyroptosis. This finding might provide a novel
      strategy for VMC treatment.

PMID- 29360866
TI  - Characterization and evaluation of avermectin solid nanodispersion prepared by
      microprecipitation and lyophilisation techniques.
AB  - Poorly water-soluble and photosensitive pesticide compounds are difficult to
      formulate as solvent-free nanoformulations with high efficacy. A avermectin solid
      nanodispersion with a mean particle size of 188 nm was developed by
      microprecipitation and lyophilisation techniques. The suspensibility and wetting
      time of the solid nanodispersion in water were 99.8% and 13 s, respectively,
      superior to those of conventional water dispersible granules and wettable
      powders. The anti-photolysis performance of the nanoformulation was twice that of
      the technical material, and the biological activity against diamondback moths was
      more than 1.5 times that of the conventional solid formulations while taking LC
      50 as the evaluation index. Moreover, the formulation composition substantially
      decreased the surfactant content and avoided organic solvents. Microprecipitation
      combined with lyophilisation is an easy and promising method to construct solid
      nanoformulations for pesticides with poor water solubility and environmental
      sensitivity. The application of the highly effective solid nanodispersion in crop
      production will have a great potential in reducing chemical residues and
      environmental pollution.

PMID- 29360868
TI  - A simple SNP genotyping method reveals extreme invasions of non-native haplotypes
      in pale chub Opsariichthys platypus, a common cyprinid fish in Japan.
AB  - Biological invasion by non-native subspecies or populations is one of the most
      serious threats to ecosystems, because these species might be easily established
      in the introduced area and can negatively affect native populations through
      competition and hybridization. Pale chub Opsariichthys platypus, one of the most
      common fish in East Asia, exhibits clear genetic differentiation among regional
      populations; however, introgression and subsequent loss of genetic integrity have
      been occurring throughout Japan due to the artificial introduction of non-native
      conspecifics. In this study, we developed a simple SNP genotyping method to
      discriminate between native and non-native mitochondrial DNA (mtDNA) haplotypes
      in pale chub using real-time PCR assay. We then investigated the distribution
      patterns of non-native pale chub in Tokai region, located in the center of Honshu
      Island, Japan and developed a predictive model of the occurrence of non-natives
      to reveal the factors influencing their invasion. The specificity and accuracy of
      the genotyping method were confirmed by using samples whose haplotypes were
      determined previously. Extensive occurrence of non-native haplotypes in Tokai
      region was detected by this method. In addition, our models suggested that the
      presence of non-natives varied greatly depending on the river system, and was
      positively influenced by the impounded water areas. Our method could accurately
      distinguish between native and non-native haplotypes of pale chub in Japan and
      suggested key environmental factors associated with the presence of non-natives.
      This approach can greatly reduce experimental costs be a great contribution for
      quantitative investigation.

PMID- 29360867
TI  - The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients
      with Essential Tremor: An articulographic study.
AB  - Acoustic studies have revealed that patients with Essential Tremor treated with
      thalamic Deep Brain Stimulation (DBS) may suffer from speech deterioration in
      terms of imprecise oral articulation and reduced voicing control. Based on the
      acoustic signal one cannot infer, however, whether this deterioration is due to a
      general slowing down of the speech motor system (e.g., a target undershoot of a
      desired articulatory goal resulting from being too slow) or disturbed
      coordination (e.g., a target undershoot caused by problems with the relative
      phasing of articulatory movements). To elucidate this issue further, we here
      investigated both acoustics and articulatory patterns of the labial and lingual
      system using Electromagnetic Articulography (EMA) in twelve Essential Tremor
      patients treated with thalamic DBS and twelve age- and sex-matched controls. By
      comparing patients with activated (DBS-ON) and inactivated stimulation (DBS-OFF)
      with control speakers, we show that critical changes in speech dynamics occur on
      two levels: With inactivated stimulation (DBS-OFF), patients showed coordination
      problems of the labial and lingual system in terms of articulatory imprecision
      and slowness. These effects of articulatory discoordination worsened under
      activated stimulation, accompanied by an additional overall slowing down of the
      speech motor system. This leads to a poor performance of syllables on the
      acoustic surface, reflecting an aggravation either of pre-existing cerebellar
      deficits and/or the affection of the upper motor fibers of the internal capsule.

PMID- 29360869
TI  - Sleep patterns and cardiometabolic risk in schoolchildren from Cuenca, Spain.
AB  - Sleep seems to have a significant influence on the metabolic syndrome (MetS).
      However, results in this association are still inconsistent in children. The aim
      of this study was to examine the influence of sleep characteristics in the MetS
      (index and factors) in Spanish children. Cross-sectional study including a sample
      of 210 children aged 8-to-11-years belonging to 20 schools from the province of
      Cuenca, Spain was conducted. Cardiometabolic risk and actigraphy sleep patterns
      were determined and analysed using correlation coefficients, ANCOVA models and a
      propensity score derivation model. Overall, children in the lower time in bed
      category and those who went to bed later (> 23:15h) showed worse values in the
      cardiometabolic profile and risk index. Differences were observed when the total
      time in bed was below 9h 15mins. Our study shows that short sleep duration could
      be a risk factor for cardiometabolic risk in children, and bedtime may
      independently influence this risk. In addition, our data suggests that children's
      sleep hygiene should be incorporated in parenting educational programs.

PMID- 29360870
TI  - Association of maternal KIR gene content polymorphisms with reduction in
      perinatal transmission of HIV-1.
AB  - The role of killer cell immunoglobulin-like receptors (KIRs) in the transmission
      of HIV-1 has not been extensively studied. Here, we investigated the association
      of KIR gene content polymorphisms with perinatal HIV-1 transmission. The KIR gene
      family comprising 16 genes was genotyped in 313 HIV-1 positive Kenyan mothers
      paired with their infants. Gene content polymorphisms were presented as presence
      of individual KIR genes, haplotypes, genotypes and KIR gene concordance. The
      genetic data were analyzed for associations with perinatal transmission of HIV.
      There was no association of infant KIR genes with perinatal HIV-1 transmission.
      After adjustment for gravidity, viral load, and CD4 cell count, there was
      evidence of an association between reduction in perinatal HIV-1 transmission and
      the maternal individual KIR genes KIR2DL2 (adjusted OR = 0.50; 95% CI: 0.24-1.02,
      P = 0.06), KIR2DL5 (adjusted OR = 0.47; 95% CI: 0.23-0.95, P = 0.04) and KIR2DS5
      (adjusted OR = 0.39; 95% CI: 0.18-0.80, P = 0.01). Furthermore, these maternal
      KIR genes were only significantly associated with reduction in perinatal HIV
      transmission in women with CD4 cell count >= 350 cells/ MUl and viral load <10000
      copies/ml. Concordance analysis showed that when both mother and child had
      KIR2DS2, there was less likelihood of perinatal HIV-1 transmission (adjusted OR =
      0.44; 95% CI: 0.20-0.96, P = 0.039). In conclusion, the maternal KIR genes
      KIR2DL2, KIR2DL5, KIR2DS5, and KIR2DS2 were associated with reduction of HIV-1
      transmission from mother to child. Furthermore, maternal immune status is an
      important factor in the association of KIR with perinatal HIV transmission.

PMID- 29360871
TI  - Dealing with taste and smell alterations-A qualitative interview study of people
      treated for lung cancer.
AB  - Taste and smell alterations have been recognized as common symptoms in relation
      to various cancers. However, previous research suggests that patients do not
      receive sufficient support in managing taste and smell alterations. Therefore,
      the objective of this study is to investigate how persons with experience from
      lung cancer-related taste and smell alterations reason about resources and
      strategies offered and used to manage these symptoms. Data from semi-structured
      individual interviews with 13 women and four men were analyzed with qualitative
      content analysis. We used Kleinman's now classic medical anthropological model of
      local health care systems, consisting of the personal, professional, and folk
      sector, to interpret and understand how people respond to sickness experiences in
      their daily lives. By presenting the findings using this model, we demonstrate
      that most strategies for dealing with taste and smell alterations were undertaken
      in the personal sector, i.e. in participants' daily lives, on an individual level
      and in interaction with family, social networks and communities. Taste and smell
      alterations implied two overarching challenges: 1) adjusting to no longer being
      able to trust information provided by one's own senses of taste and/or smell, and
      2) coming to terms with taste and smell alterations as a part of having lung
      cancer. Health care professionals' involvement was described as limited, but
      appeared to fulfil most participants' expectations. However, through provision of
      normalizing information, practical advice, and to some extent, emotional support,
      health care professionals had potential to influence strategies and resources
      used for dealing with taste and smell alterations. With this study, we further
      the understanding of how people deal with lung cancer-related taste and smell
      alterations and discuss the role of health care professionals for this process.

PMID- 29360872
TI  - Mobile tablet-based therapies following stroke: A systematic scoping review of
      administrative methods and patient experiences.
AB  - BACKGROUND AND PURPOSE: Stroke survivors are often left with deficits requiring
      rehabilitation to recover function and yet, many are unable to access
      rehabilitative therapies. Mobile tablet-based therapies (MTBTs) may be a resource
      efficient means of improving access to timely rehabilitation. It is unclear what
      MTBTs have been attempted following stroke, how they were administered, and how
      patients experienced the therapies. The review summarizes studies of MTBTs
      following stroke in terms of administrative methods and patient experiences to
      inform treatment feasibility. METHODS: Articles were eligible if they reported
      the results of an MTBT attempted with stroke participants. Six research databases
      were searched along with grey literature sources, trial registries, and article
      references. Intervention administration details and patient experiences were
      summarized. RESULTS: The search returned 903 articles of which 23 were eligible
      for inclusion. Most studies were small, observational, and enrolled chronic
      stroke patients. Interventions commonly targeted communication, cognition, or
      fine-motor skills. Therapies tended to be personalized based on patient deficits
      using commercially available applications. The complexity of therapy
      instructions, fine-motor requirements, and unreliability of internet or cellular
      connections were identified as common barriers to tablet-based care. CONCLUSIONS:
      Stroke patients responded positively to MTBTs in both the inpatient and home
      settings. However, some support from therapists or caregivers may be required for
      patients to overcome barriers to care. Feasibility studies should continue to
      identify the administrative methods that minimize barriers to care and maximize
      patient adherence to prescribed therapy regiments.

PMID- 29360873
TI  - Neisseria gonorrhoeae co-infection exacerbates vaginal HIV shedding without
      affecting systemic viral loads in human CD34+ engrafted mice.
AB  - HIV synergy with sexually transmitted co-infections is well-documented in the
      clinic. Co-infection with Neisseria gonorrhoeae in particular, increases genital
      HIV shedding and mucosal transmission. However, no animal model of co-infection
      currently exists to directly explore this relationship or to bridge the gap in
      understanding between clinical and in vitro studies of this interaction. This
      study aims to test the feasibility of using a humanized mouse model to overcome
      this barrier. Combining recent in vivo modelling advancements in both HIV and
      gonococcal research, we developed a co-infection model by engrafting
      immunodeficient NSG mice with human CD34+ hematopoietic stem cells to generate
      humanized mice that permit both systemic HIV infection and genital N. gonorrhoeae
      infection. Systemic plasma and vaginal lavage titres of HIV were measured in
      order to assess the impact of gonococcal challenge on viral plasma titres and
      genital shedding. Engrafted mice showed human CD45+ leukocyte repopulation in
      blood and mucosal tissues. Systemic HIV challenge resulted in 104-105 copies/mL
      of viral RNA in blood by week 4 post-infection, as well as vaginal shedding of
      virus. Subsequent gonococcal challenge resulted in unchanged plasma HIV levels
      but higher viral shedding in the genital tract, which reflects published clinical
      observations. Thus, human CD34+ stem cell-transplanted NSG mice represent an
      experimentally tractable animal model in which to study HIV shedding during
      gonococcal co-infection, allowing dissection of molecular and immunological
      interactions between these pathogens, and providing a platform to assess future
      therapeutics aimed at reducing HIV transmission.

PMID- 29360874
TI  - Disparities in health care outcomes between immigrants and the majority
      population in Germany: A trend analysis, 2006-2014.
AB  - BACKGROUND: Immigrants often encounter barriers in the health system that may
      affect their health care outcomes. In order to better cater to the needs of
      immigrants, many health care institutions have increased their efforts in recent
      years to provide services which are more sensitive to the needs of an
      increasingly diverse population. Little is known about whether these efforts are
      successful. This study examines difference in outcomes of tertiary prevention
      between immigrants and the autochthonous population in Germany over the period of
      2006-2014. METHODS: The analysis is based on a 10% random sample of routine data
      on completed tertiary preventive treatments in Germany during 2006-2014. Four
      different indicators of treatment effectiveness were compared between patients
      with a nationality from Germany, Portugal/Spain/Italy/Greece, Turkey and Former
      Yugoslavia using logistic regression adjusted for demographic/socioeconomic
      factors. Interaction terms for year were modeled to examine group differences
      over time. RESULTS: Depending on the outcome, Turkish and Former Yugoslavian
      nationals had an 23%-69% higher chance of a poor treatment effectiveness than
      Germans (OR = 1.23 [95%-CI = 1.15,1.32] and OR = 1.69 [95%-CI = 1.55,1.83],
      respectively). Fewer differences were observed between nationals from
      Portugal/Spain/Italy/Greece and Germans. Disparities did not significantly differ
      between the years in which services were utilized. CONCLUSION: Measures
      implemented by health care institutions did not reduce existing health care
      disparities between immigrants and the majority population in Germany. One
      potential reason is that existing approaches are unsystematic and often not
      properly evaluated. More targeted strategies and a thorough evaluation is needed
      in order to improve health care for immigrants sustainably.

PMID- 29360875
TI  - Predictive modeling of emergency cesarean delivery.
AB  - OBJECTIVE: To increase discriminatory accuracy (DA) for emergency cesarean
      sections (ECSs). STUDY DESIGN: We prospectively collected data on and studied all
      6,157 births occurring in 2014 at four public hospitals located in three
      different autonomous communities of Spain. To identify risk factors (RFs) for
      ECS, we used likelihood ratios and logistic regression, fitted a classification
      tree (CTREE), and analyzed a random forest model (RFM). We used the areas under
      the receiver-operating-characteristic (ROC) curves (AUCs) to assess their DA.
      RESULTS: The magnitude of the LR+ for all putative individual RFs and ORs in the
      logistic regression models was low to moderate. Except for parity, all putative
      RFs were positively associated with ECS, including hospital fixed-effects and
      night-shift delivery. The DA of all logistic models ranged from 0.74 to 0.81. The
      most relevant RFs (pH, induction, and previous C-section) in the CTREEs showed
      the highest ORs in the logistic models. The DA of the RFM and its most relevant
      interaction terms was even higher (AUC = 0.94; 95% CI: 0.93-0.95). CONCLUSION:
      Putative fetal, maternal, and contextual RFs alone fail to achieve reasonable DA
      for ECS. It is the combination of these RFs and the interactions between them at
      each hospital that make it possible to improve the DA for the type of delivery
      and tailor interventions through prediction to improve the appropriateness of ECS
      indications.

PMID- 29360876
TI  - Longitudinal network structure of depression symptoms and self-efficacy in low
      income mothers.
AB  - Maternal depression was recently conceptualized as a network of interacting
      symptoms. Prior studies have shown that low self-efficacy, as an index of
      maternal functioning, is one important source of stress that worsens depression.
      We have limited information, however, on the specific relationships between
      depression symptoms and self-efficacy. In this study, we used regularized partial
      correlation networks to explore the multivariate relationships between maternal
      depression symptoms and self-efficacy over time. Depressed mothers (n = 306)
      completed the Center for Epidemiological Studies Depression (CES-D) scale at four
      time points, between four and eight weeks apart. We estimated (a) the network
      structure of the 20 CES-D depression symptoms and self-efficacy for each time
      point, (b) determined the centrality or structural importance of all variables,
      and (c) tested whether the network structure changed over time. In the resulting
      networks, self-efficacy was mostly negatively connected with depression symptoms.
      The strongest relationships among depression symptoms were 'lonely-sleep
      difficulties' and 'inability to get going-crying'. 'Feeling disliked' and
      'concentration difficulty' were the two most central symptoms. In comparing the
      network structures, we found that the network structures were moderately stable
      over time. This is the first study to investigate the network structure and their
      temporal stability of maternal depression symptoms and self-efficacy in low
      income depressed mothers. We discuss how these findings might help future
      research to identify clinically relevant symptom-to-symptom relationships that
      could drive maternal depression processes, and potentially inform tailored
      interventions. We share data and analytical code, making our results fully
      reproducible.

PMID- 29360877
TI  - Biotin-tagged proteins: Reagents for efficient ELISA-based serodiagnosis and
      phage display-based affinity selection.
AB  - The high-affinity interaction between biotin and streptavidin has opened avenues
      for using recombinant proteins with site-specific biotinylation to achieve
      efficient and directional immobilization. The site-specific biotinylation of
      proteins carrying a 15 amino acid long Biotin Acceptor Peptide tag (BAP; also
      known as AviTag) is effected on a specific lysine either by co-expressing the E.
      coli BirA enzyme in vivo or by using purified recombinant E. coli BirA enzyme in
      the presence of ATP and biotin in vitro. In this paper, we have designed a T7
      promoter-lac operator-based expression vector for rapid and efficient cloning,
      and high-level cytosolic expression of proteins carrying a C-terminal BAP tag in
      E. coli with TEV protease cleavable N-terminal deca-histidine tag, useful for
      initial purification. Furthermore, a robust three-step purification pipeline
      integrated with well-optimized protocols for TEV protease-based H10 tag removal,
      and recombinant BirA enzyme-based site-specific in vitro biotinylation is
      described to obtain highly pure biotinylated proteins. Most importantly, the
      paper demonstrates superior sensitivities in indirect ELISA with directional and
      efficient immobilization of biotin-tagged proteins on streptavidin-coated
      surfaces in comparison to passive immobilization. The use of biotin-tagged
      proteins through specific immobilization also allows more efficient selection of
      binders from a phage-displayed naive antibody library. In addition, for both
      these applications, specific immobilization requires much less amount of protein
      as compared to passive immobilization and can be easily multiplexed. The
      simplified strategy described here for the production of highly pure biotin
      tagged proteins will find use in numerous applications, including those, which
      may require immobilization of multiple proteins simultaneously on a solid
      surface.

PMID- 29360878
TI  - Neighbourhood disadvantage, geographic remoteness and body mass index among
      immigrants to Australia: A national cohort study 2006-2014.
AB  - Obesity is socioeconomically, geographically and ethnically patterned.
      Understanding these elements of disadvantage is vital in understanding population
      obesity trends and the development of effective and equitable interventions. This
      study examined the relationship between neighbourhood socioeconomic disadvantage
      and geographic remoteness with prospective trends in mean body mass index (BMI)
      among immigrants to Australia. Longitudinal data (2006-2014) from a national
      panel survey of Australian adults was divided into an immigrant-only sample (n =
      4,293, 52.6% women and 19,404 person-year observations). The data were analysed
      using multi-level random effects linear regression modelling that controlled for
      individual socioeconomic and demographic factors. Male immigrants living in the
      most disadvantaged neighbourhoods had significantly higher mean BMI compared with
      those living in the least disadvantaged. Over time, mean BMI increased for all
      groups except for men living in the least disadvantaged neighbourhoods, for whom
      mean BMI remained almost static (0.1 kg/m2 increase from 2006 to 2014),
      effectively widening neighbourhood inequalities. Among women, mean BMI was also
      significantly higher in the most compared with the least, disadvantaged
      neighbourhoods (beta = 2.08 kg/m2; 95%CI: 1.48, 2.68). Neighbourhood inequalities
      were maintained over time as mean BMI increased for all groups at a similar rate.
      Male and female immigrants residing in outer regional areas had significantly
      higher mean BMI compared with those living in major cities; however, differences
      were attenuated and no longer significant following adjustment for ethnicity,
      individual socioeconomic position and neighbourhood disadvantage. Over time, mean
      BMI increased in all male and female groups with no differences based on
      geographic remoteness. Obesity prevention policy targeted at immigrant cohorts
      needs to include area-level interventions that address inequalities in BMI
      arising from neighbourhood disadvantage, and be inclusive of immigrants living
      outside Australia's major cities.

PMID- 29360879
TI  - Different outcome of sarcoglycan missense mutation between human and mouse.
AB  - Sarcoglycanopathies are rare autosomic limb girdle muscular dystrophies caused by
      mutations in one of the genes coding for sarcoglycan (alpha, beta, delta, and
      gamma-sarcoglycans). Sarcoglycans form a complex, which is an important part of
      the dystrophin-associated glycoprotein complex that protects sarcolemma against
      muscle contraction-induced damages. Absence of one of the sarcoglycan at the
      plasma membrane induces the disappearance of the whole complex and perturbs
      muscle fiber membrane integrity. We previously demonstrated that point mutations
      in the human sarcoglycan genes affects the folding of the corresponding protein,
      which is then retained in the endoplasmic reticulum by the protein quality
      control and prematurely degraded by the proteasome. Interestingly, modulation of
      the quality control using pharmacological compounds allowed the rescue of the
      membrane localization of the mutated sarcoglycan. Two previously generated mouse
      models, knock-in for the most common sarcoglycan mutant, R77C alpha-sarcoglycan,
      failed in reproducing the dystrophic phenotype observed in human patients. Based
      on these results and the need to test therapies for these fatal diseases, we
      decided to generate a new knock-in mouse model carrying the missense mutation
      T151R in the beta-sarcoglycan gene since this is the second sarcoglycan protein
      with the most frequently reported missense mutations. Muscle analysis, performed
      at the age of 4 and 9-months, showed the presence of the mutated beta-sarcoglycan
      protein and of the other components of the dystrophin-associated glycoprotein
      complex at the muscle membrane. In addition, these mice did not develop a
      dystrophic phenotype, even at a late stage or in condition of stress-inducing
      exercise. We can speculate that the absence of phenotype in mouse may be due to a
      higher tolerance of the endoplasmic reticulum quality control for amino-acid
      changes in mice compared to human.

PMID- 29360881
TI  - Healthcare professionals' views of the experiences of individuals living with
      Crohn's Disease in Spain. A qualitative study.
AB  - Crohn's Disease (CD) in Spain lacks of a unified National Clinical Pathway and
      not even any early detection program and professional follow-up outpatient
      attention once it has been diagnosed. Little is known about the Spanish health
      professionals' views of the experiences of individuals living with Crohn's
      Disease nationwide and also about how the Spanish Health System faces this
      situation. A qualitative research method was conducted to explore this topic
      through in-depth interviews with eleven healthcare professionals, who represented
      different clinics treating people with CD from the province of Alicante (Spain).
      Three topics and seven sub-topics were derived from the analysis of the content
      emerging from the interviews. The three main topics were: the healthcare system
      as a hindrance for ongoing treatment of CD, the impact of the disease, support
      networks. The knowledge of CD gained by healthcare professionals, in the contexts
      studied here within, with regards to the psychosocial aspects and the experience
      of those living with the disease and their immediate circles, is poor, if not
      null on an academic level, becoming experiential on their incorporation into the
      professional field. Additionally, a priori, they lack the tools to address the
      doubts and concerns of patients from the moment of diagnosis through the ongoing
      care of the patient. Organizational hindrances, such as the lack of time and
      consensual guidelines for adequately monitoring CD patients in Alicante (Spain),
      further restrict the patient-professional relationship. Due to the consensus
      established by the National Agency regulating the contents of the Health
      Professions' Education and Training across the country, we are assuming that the
      phenomenon highlighted may be similar in other parts of Spain. Therefore, it can
      be said that healthcare professionals have a limited understanding of the impact
      of CD on the day-to-day life of those affected, not being considered a part of
      the CD patients' formal support network. Nonetheless, they are conscious of this
      limitation and advocate for multidisciplinary teams as the best means of
      attending to people living with CD. Our study outcomes may represent the first
      step onto identifying strategies and best practices for establishing an effective
      therapeutic relationship, as well as any hindering factors.

PMID- 29360880
TI  - What's the risk? Identifying potential human pathogens within grey-headed flying
      foxes faeces.
AB  - Pteropus poliocephalus (grey-headed flying foxes) are recognised vectors for a
      range of potentially fatal human pathogens. However, to date research has
      primarily focused on viral disease carriage, overlooking bacterial pathogens,
      which also represent a significant human disease risk. The current study applied
      16S rRNA amplicon sequencing, community analysis and a multi-tiered database OTU
      picking approach to identify faecal-derived zoonotic bacteria within two colonies
      of P. poliocephalus from Victoria, Australia. Our data show that sequences
      associated with Enterobacteriaceae (62.8% +/- 24.7%), Pasteurellaceae (19.9% +/-
      25.7%) and Moraxellaceae (9.4% +/- 11.8%) dominate flying fox faeces. Further
      colony specific differences in bacterial faecal colonisation patterns were also
      identified. In total, 34 potential pathogens, representing 15 genera, were
      identified. However, species level definition was only possible for Clostridium
      perfringens, which likely represents a low infectious risk due to the low
      proportion observed within the faeces and high infectious dose required for
      transmission. In contrast, sequences associated with other pathogenic species
      clusters such as Haemophilus haemolyticus-H. influenzae and Salmonella bongori-S.
      enterica, were present at high proportions in the faeces, and due to their
      relatively low infectious doses and modes of transmissions, represent a greater
      potential human disease risk. These analyses of the microbial community
      composition of Pteropus poliocephalus have significantly advanced our
      understanding of the potential bacterial disease risk associated with flying
      foxes and should direct future epidemiological and quantitative microbial risk
      assessments to further define the health risks presented by these animals.

PMID- 29360882
TI  - Lack of sleep is associated with internet use for leisure.
AB  - OBJECTIVE: Previous studies have suggested that excessive internet use may cause
      lack of sleep. However, recent studies have hypothesized that lack of sleep may
      instigate internet use for leisure. To elucidate the potential effects of sleep
      time on internet use, we explored the different associations between sleep time
      and internet use according to its purpose. METHODS: The population-based, cross
      sectional study group from the Korea Youth Risk Behavior Web-based Survey
      (KYRBWS) collected data from 57,425 middle school students in 2014 and 2015.
      Sleep time over the past 7 days was classified into the following groups: < 7 h
      (6 h); >= 7 h, < 8 h (7 h); >= 8 h, < 9 h (8 h); and >= 9 h (9+ h). Internet use
      time per day was separately surveyed for leisure and for study and categorized as
      follows: 0 h; > 0 h, <= 1 h (1 h); > 1 h, <= 2 h (2 h); and > 2 h (2+ h) per day.
      Information on age, sex, region of residence, body mass index (BMI), economic
      level, parental education level, stress level, school performance level, and
      sleep satisfaction were retrieved. The relationships between sleep time and
      internet use time for leisure/study were analyzed using multinomial logistic
      regression with complex sampling. In the subgroup analysis according to sleep
      satisfaction (good, normal, and poor), the associations of sleep time with
      internet use for leisure were analyzed using the same methods. RESULTS: Compared
      to 9+ h of sleep, less sleep was related to a long internet use time (2+ h) for
      leisure (adjusted odds ratio, AOR [95% confidence interval, CI] of sleep: 8 h =
      1.23 [1.14-1.32]; 7 h = 1.42 [1.31-1.54]; and 6 h = 1.56 [1.44-1.70]; P < 0.001).
      Conversely, a relationship between less sleep and a long internet use time (2+ h)
      for study was evident only for 6 h of sleep (AOR of sleep: 8 h = 0.84 [0.84
      1.04]; 7 h = 1.05 [0.94-1.17]; and 6 h = 1.32 [1.27-1.59]; P < 0.001). In the
      subgroup analysis according to sleep satisfaction, less sleep was associated with
      a long internet use time for leisure in all sleep satisfaction groups, although
      the relationship was more significant in the lower sleep satisfaction group.
      CONCLUSION: Less sleep was significantly related to long-term use of the internet
      for leisure, whereas this association was not definite for internet use for
      study. Furthermore, poor sleep quality potentiated the relationship between less
      sleep time and internet use for leisure.

PMID- 29360884
TI  - Relationship between socioeconomic status and gastrointestinal infections in
      developed countries: A systematic review and meta-analysis.
AB  - BACKGROUND: The association between socioeconomic status (SES) and health is well
      documented; however limited evidence on the relationship between SES and
      gastrointestinal (GI) infections exists, with published studies producing
      conflicting results. This systematic review aimed to assess the association
      between SES and GI infection risk, and explore possible sources of heterogeneity
      in effect estimates reported in the literature. METHODS: MEDLINE, Scopus, Web of
      Science and grey literature were searched from 1980 to October 2015 for studies
      reporting an association between GI infections and SES in a representative
      population sample from a member-country of the Organisation for Economic Co
      operation and Development. Harvest plots and meta-regression were used to
      investigate potential sources of heterogeneity such as age; level of SES
      variable; GI infection measurement; and predominant mode of transmission. The
      protocol was registered on PROSPERO: CRD42015027231. RESULTS: In total, 6021
      studies were identified; 102 met the inclusion criteria. Age was identified as
      the only statistically significant potential effect modifier of the association
      between SES and GI infection risk. For children, GI infection risk was higher for
      those of lower SES versus high (RR 1.51, 95% CI;1.26-1.83), but there was no
      association for adults (RR 0.79, 95% CI;0.58-1.06). In univariate analysis, the
      increased risk comparing low and high SES groups was significantly higher for
      pathogens spread by person-to-person transmission, but lower for environmental
      pathogens, as compared to foodborne pathogens. CONCLUSIONS: Disadvantaged
      children, but not adults, have greater risk of GI infection compared to their
      more advantaged counterparts. There was high heterogeneity and many studies were
      of low quality. More high quality studies are needed to investigate the
      association between SES and GI infection risk, and future research should
      stratify analyses by age and pathogen type. Gaining further insight into this
      relationship will help inform policies to reduce inequalities in GI illness in
      children.

PMID- 29360885
TI  - Purinergic signaling in B cells.
AB  - Adenosine and adenosine triphosphate are involved in purinergic signaling which
      plays an important role in control of the immune system. Much data have been
      obtained regarding impact of purinergic signaling on dendritic cells,
      macrophages, monocytes and T lymphocytes, however less attention has been paid to
      purinergic regulation of B cells. This review summarizes present knowledge on ATP
      and Ado-dependent signaling in B lymphocytes. Human B cells have been shown to
      express A1-AR, A2A-AR, A2B-AR and A3-AR and each subtype of P2 receptors. Surface
      of B cells exhibits two antagonistic ectoenzymatic pathways, one relies on
      constitutive secretion and resynthesis of ATP, while the second one depends on
      degradation of adenosine nucleotides to nucleosides and their subsequent
      degradation. Inactivated B cells remain under the suppressive impact of autocrine
      and paracrine Ado, whereas activated B lymphocytes increase ATP release and
      production. ATP protects B cells from Ado-induced suppression and exerts pro
      inflammatory effect on the target tissues, and it is also involved in the IgM
      release. On the other hand, Ado synthesis is necessary for optimal development,
      implantation and maintenance of the plasmocyte population in bone marrow in the
      course of the primary immune response. Moreover, Ado plays an important role in
      immunoglobulin class switching, which is a key mechanism of humoral immune
      response. Disruption of purinergic signaling leads to severe disorders.
      Impairment of Ado metabolism is one of the factors responsible for common
      variable immunodeficiency. There are several lines of evidence that dysfunction
      of the immune system observed during diabetes may in part depend on disrupted ATP
      and Ado metabolism in the B cells.

PMID- 29360883
TI  - Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed
      nanoparticles targeting the lungs for protection against pneumococcal infection.
AB  - Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the
      availability of conjugate vaccines. Mucosal immunization targeting the lungs is
      an attractive alternative for the induction of local immune responses to improve
      protection against pneumonia. Our group had previously described the development
      of poly(glycerol adipate-co-omega-pentadecalactone) (PGA-co-PDL) polymeric
      nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4
      (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs)
      for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was
      now used for immunization of mice. Inoculation of this formulation induced anti
      PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to
      intact bacteria showed efficient binding to bacteria expressing PspA from clades
      3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1
      and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro
      and subcutaneous injection of the protein elicited partial protection against
      intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA
      from clade 5 (PspA5). Although similar survival levels were observed for mucosal
      immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified
      protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely,
      neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with
      purified protein reduced bacterial burden in the lungs after challenge with a
      serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization
      with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and
      systemic antibodies, conferring protection only against a strain expressing PspA
      from the homologous family 2.

PMID- 29360886
TI  - Multinucleate cell angiohistiocytoma.
AB  - Multinucleate cell angiohistiocytoma (MCAH) is a rare cutaneous entity described
      as grouped erythematous to violaceous papules. Histopathologic findings include
      vascular proliferations with multinucleate giant cells and dermal fibrosis. We
      report a case of MCAH in an 83-year-old white man affecting both the right
      anterior thigh and left posterior calf. Additionally, the pathogenesis of MCAH
      and different therapeutic modalities are reviewed.

PMID- 29360887
TI  - The h-index for associate and full professors of dermatology in the United
      States: an epidemiologic study of scholastic production.
AB  - Promotion in academic dermatology requires evidence of scholastic production. The
      h-index is a bibliometric measure that combines both volume and impact of
      scientific contributions. Its calculation better predicts future scientific
      success than do publication or citation counts. In this epidemiologic survey of
      associate and full professors of dermatology in residency training programs in
      the United States, we measured mean and median h-indices among associate and full
      professors as well as regional differences in h-index. These findings could be
      used to track individual achievement and as a parameter in considering an
      individual for professional advancement in dermatology.

PMID- 29360888
TI  - Direct and indirect patient costs of dermatology clinic visits and their impact
      on access to care and provider preference.
AB  - The direct and indirect costs of dermatology clinic visits are infrequently
      quantified. Indirect costs, such as the time spent traveling to and from
      appointments and the value of lost earnings from time away from work, are
      substantial costs that often are not included in economic analyses but may pose
      barriers to receiving care. Due to the national shortage of dermatologists,
      patients may have to wait longer for appointments or travel further to see
      dermatologists outside of their local community, resulting in high time and
      travel costs for patients. Patients' lost time and earnings comprise the
      opportunity cost of obtaining care. A monetary value for this opportunity cost
      can be calculated by multiplying a patient's hourly wage by the number of hours
      that the patient dedicated to attending the dermatology appointment. Using a
      single institution survey, this study quantified the direct and indirect patient
      costs, including opportunity costs and time burden, associated with dermatology
      clinic visits to better appreciate the impact of these factors on health care
      access and dermatologic provider preference.

PMID- 29360889
TI  - Student loan burden and its impact on career decisions in dermatology.
AB  - Dermatology departments in the United States face difficulties in recruiting
      dermatologists to academic positions, raising concerns for the future of
      dermatology education and research. This preliminary study aimed to explore the
      impact of student loan burden on career plans in dermatology and to determine if
      the Public Service Loan Forgiveness (PSLF) program can be used as a recruitment
      tool for academic positions in dermatology. Results from this electronic survey,
      which was distributed to dermatology residents and attending physicians, revealed
      that debt burden may influence career decisions in dermatology. Dermatologists
      may not be fully educated on loan repayment options. With increased awareness,
      the PSLF can potentially be used as a recruitment tool for academic positions in
      dermatology.

PMID- 29360890
TI  - Lichen planus pemphigoides treated with ustekinumab.
AB  - A 71-year-old woman presented with pink to violaceous, flat-topped, polygonal
      papules on the volar wrists, extensor elbows, and bilateral lower legs of 3
      years' duration. She also had erythematous, violaceous, infiltrated plaques with
      microvesiculation on the bilateral thighs of several months' duration. She
      reported pruritus, burning, and discomfort. Her medical history included type 2
      diabetes mellitus, hypertension, and asthma with no history of skin rashes.
      Workup revealed lichen planus pemphigoides (LPP), a rare papulosquamous and
      vesiculobullous dermatosis that shares features of both lichen planus (LP) and
      bullous pemphigoid (BP). Despite multiple traditional therapies, her disease
      continued to progress, further developing mucosal disease. After a review of the
      literature on LP, BP, and LPP, it was noted that tumor necrosis factor alpha (TNF
      alpha), along with other cytokines, plays a pivotal role in all 3 diseases. After
      several conventional systemic therapies failed, we treated our patient with
      ustekinumab with favorable results.

PMID- 29360891
TI  - Pediatric nevoid basal cell carcinoma syndrome.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, autosomal-dominant,
      cancer-predisposing, multisystem disorder. The clinical manifestations of NBCCS
      include multiple basal cell carcinomas (BCCs), odontogenic keratocysts, palmar or
      plantar pits, and calcification of the falx cerebri. We present a case of an 11
      year-old boy with Fitzpatrick skin type V who presented with multiple facial
      lesions and a history of maxillary keratocysts. Skin biopsy was consistent with
      pigmented BCC of the right nasolabial fold. Further clinical workup revealed
      multiple pigmented BCCs, palmoplantar pits, and calcification of the tentorium.
      Genetic testing revealed a heterozygous mutation in the patched 1 gene, PTCH1,
      consistent with NBCCS. This case highlights the treatment considerations in
      pediatric cases of NBCCS in Fitzpatrick skin type V patients.

PMID- 29360892
TI  - Long-term pubic dermatitis diagnosed as white piedra.
AB  - The case of a 58-year-old man with a pruritic rash involving the pubic area that
      had been undiagnosed for 30 years is presented. At least 15 different primary
      care physicians and dermatologists evaluated the patient during this time period.
      Multiple treatments were unsuccessful and a definitive diagnosis was not
      rendered. Wood lamp evaluation of the pubic area revealed hair shaft concretions
      that were confirmed on histologic evaluation to be white piedra (WP). The patient
      was successfully treated with topical ketoconazole and the eruption completely
      resolved. Our case raises awareness of the use of Wood lamp and dermoscopy to
      evaluate for parasitic infections of the pubic hair shafts when nonspecific
      dermatitis presents in this area.

PMID- 29360893
TI  - Sjogren-Larsson syndrome: definitive diagnosis on magnetic resonance
      spectroscopy.
AB  - Sjogren-Larsson syndrome (SLS) is a rare autosomal-recessive neurocutaneous
      disorder comprising a triad of ichthyosis, mental retardation, and spastic
      diplegia or quadriplegia. It has rarely been reported in Asian and Indian
      populations. We report the case of an Indian patient with SLS who presented with
      the classical clinical triad and demonstrated characteristic findings on magnetic
      resonance spectroscopy. In resource-restricted settings where enzymatic and
      genetic analyses are not available, magnetic resonance spectroscopy serves as a
      useful adjunct in confirming the diagnosis of SLS.

PMID- 29360894
TI  - Diversity in the dermatology workforce: 2017 status update.

PMID- 29360895
TI  - Cordlike dermal plaques and nodules on the neck and hands.

PMID- 29360896
TI  - Indurated plaque on the eyebrow.

PMID- 29360897
TI  - The effects of sunscreen on marine environments.

PMID- 29360898
TI  - Approach to treatment of medical and cosmetic facial concerns in skin of color
      patients.
AB  - Facial concerns in skin of color (SOC) patients vary and can be a source of
      emotional and psychological distress. This article discusses 4 common facial
      concerns in SOC patients: acne, rosacea, facial hyperpigmentation, and cosmetic
      enhancement. Treatment recommendations are provided as well as management pearls.

PMID- 29360899
TI  - Pediatric periorificial dermatitis.
AB  - Periorificial dermatitis (POD) has been documented in the pediatric population in
      patients as young as 3 months, with a slight predominance in girls compared to
      boys. Many patients have a personal or family history of atopic disorders.
      Periorificial dermatitis typically presents with erythematous to flesh-colored
      papules and rarely pustules near the eyes, nose, and mouth. Although the etiology
      is unknown, many patients have had recent exposure to a topical or less commonly
      an inhaled or systemic corticosteroid. Although steroids may initially control
      the skin lesions, disease often rebounds after discontinuing therapy. Diagnosis
      of POD is clinical. Laboratory tests are not helpful in making the diagnosis, and
      the histology of POD resembles rosacea. It is important to rule out other
      acneform diagnoses based on the age of the patient, clinical history, and
      presentation of the lesions. Topical metronidazole has been successful in the
      pediatric population. For pediatric patients with extrafacial skin lesions or
      more severe disease, oral antibiotics such as tetracycline, doxycycline,
      minocycline, azithromycin, and erythromycin can be used, depending on the age of
      the patient.

PMID- 29360900
TI  - What's eating you? head lice (Pediculus humanus capitis).
AB  - The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the
      suborder Anoplura. Infestation continues in epidemic proportions in children of
      all socioeconomic groups. Although not implicated as a disease vector,
      infestation can lead to considerable distress, missed days of school, and
      secondary infections. Pyrethroids are recommended for treatment, but resistance
      is common. Newer agents, including benzyl alcohol and spinosad, have been
      developed to address this gap in care.

PMID- 29360901
TI  - Red patches on a newborn.

PMID- 29360902
TI  - Genital ulcers and swelling in an adolescent girl.

PMID- 29360903
TI  - Richner-Hanhart syndrome (tyrosinemia type II).

PMID- 29360904
TI  - Pseudomyogenic hemangioendothelioma.
AB  - Pseudomyogenic hemangioendothelioma (PMHE) is a rare vascular tumor that was
      added to the World Health Organization classification of soft tissue tumors.
      These tumors have a unique clinical presentation and microscopic appearance as
      compared to other vascular tumors in the differential diagnosis. Unlike its
      microscopic mimicker epithelioid sarcoma, PMHE rarely metastasizes and long-term
      survival in affected patients is excellent. In this report, we present a patient
      with PMHE and review the current literature on clinical presentation and
      histologic differentiation of this unique tumor, comparing findings to its
      mimickers.

PMID- 29360905
TI  - Disfiguring ulcerative neutrophilic dermatosis secondary to doxycycline and
      isotretinoin in an adolescent boy with acne conglobata.
AB  - Acne fulminans is an uncommon and debilitating disease that presents as an acute
      eruption of nodular and ulcerative acne lesions in association with systemic
      symptoms. It occurs commonly during treatment of severe acne (eg, acne
      conglobata) with isotretinoin in young adolescent male patients. Isotretinoin and
      doxycycline also can potentially induce development of neutrophilic dermatoses in
      patients with severe acne lesions, which are characterized by the acute
      appearance of painful ulcerative papulonodules accompanied by systemic symptoms
      including fever and leukocytosis. We report a challenging case of a 13-year-old
      adolescent boy who acutely developed hundreds of ulcerative plaques as well as
      systemic symptoms after being treated with doxycycline and isotretinoin for acne
      conglobata. He was treated with prednisone, dapsone, and colchicine and had to
      switch to cyclosporine to achieve relief from his condition.

PMID- 29360906
TI  - Pediatric leg ulcers: going out on a limb for the diagnosis.
AB  - This article exhibits the most common differential diagnoses for pediatric leg
      ulcers and contrasts the etiologies with the adult population. The diagnoses are
      further categorized into hematologic, infectious, genodermatoses, and autoimmune
      etiologies to help the dermatologist deduce the accurate diagnosis in this unique
      patient population.

PMID- 29360907
TI  - Lichen planus and lichenoid drug eruption after vaccination.
AB  - Lichen planus (LP) and lichenoid drug eruptions (LDEs) uncommonly occur after
      vaccination, especially for hepatitis B and influenza. The key initiating event
      that leads to the development of postimmunization LP or LDE is not well
      understood. There have been prior reports of an association between several
      vaccines and LP. In this study, we aim to characterize and review cases of LP and
      LDE after vaccination from the Vaccine Adverse Event Reporting System (VAERS)
      national database in the United States. Information on vaccine-associated LP and
      LDE was retrieved from the database (July 1990 to November 2014) to examine the
      frequency of LP or LDE after vaccination. Hepatitis B, influenza, and herpes
      zoster vaccines were the 3 most commonly associated vaccines. Patients with LP or
      LDE were significantly older compared to the reported adverse events (AEs)
      overall (P<.001). The median age of onset for LP and LDE was 47 years. The median
      time of onset of AEs was 14 days. It is important to obtain recent vaccination
      history in patients presenting with new-onset LP or LDE.

PMID- 29360913
TI  - Commentary on: Application of a Porous Polyethylene Spreader Graft for Nasal
      Lengthening in Asian Patients.

PMID- 29360914
TI  - RAISEing VEGF-D's importance as predictive biomarker for ramucirumab in
      metastatic colorectal cancer patients.

PMID- 29360916
TI  - Seroma Rates Are Not Increased When Combining Liposuction With Progressive
      Tension Suture Abdominoplasty: A Retrospective Cohort Study of 619 Patients.
AB  - Background: Several studies have demonstrated that progressive tension sutures
      (PTS) reduce seroma. Many fear that adding liposuction to abdominoplasty will
      increase seroma rates and avoid drainless abdominoplasty when performing
      concomitant liposuction. Objectives: We sought to identify whether liposuction
      increases seroma in PTS and non-PTS abdominoplasty. Methods: In this
      retrospective study, 619 patients underwent abdominoplasty between 2009 and 2017,
      of which 299 patients had drainless abdominoplasty with PTS and 320 had drain
      based abdominoplasty. We compared complications among PTS patients with and
      without liposuction and among drain-based abdominoplasty patients with and
      without liposuction. Results: Demographics were similar between PTS and drain
      patients and between liposuction and nonliposuction PTS. Mean liposuction volume
      with PTS was 1592 +/- 1048 mL. Seroma in the PTS group was found to be 2.6%,
      which is consistent with previous data. PTS without liposuction had a rate of
      seroma of 6.67% compared to a rate of 2.2% with liposuction; these rates were not
      significantly different (P = 0.20). A total of 207 patients had drain-based
      abdominoplasty with liposuction, and 113 had it without liposuction. Seroma with
      liposuction was 9.17% and without liposuction was 6.19%, although these
      differences were not significant (P = 0.52). PTS lipoabdominoplasty had less
      seroma compared with drain-based lipoabdominoplasty (P = 0.01). Conclusions:
      Liposuction was performed in 80% of the patients, and patients with
      lipoabdominoplasty were not at a higher risk of seroma, in the drain group or the
      PTS group. More patients may allow validation that liposuction may actually be
      protective with PTS. Regardless, there is no increase in seroma with the addition
      of liposuction to PTS drainless abdominoplasty. Level of Evidence 3: 

PMID- 29360915
TI  - The Effects of eGFR Change on CVD, Renal, and Mortality Outcomes in a
      Hypertensive Cohort Treated With 3 Different Antihypertensive Medications.
AB  - BACKGROUND: Impaired renal function is a risk factor for cardiovascular disease,
      end-stage renal disease (ESRD), and mortality. The impact of short-term renal
      function decline on outcomes is less well studied. The association of
      antihypertensive medications with the impact of short-term estimated glomerular
      filtration rate (eGFR) decline is not known. METHODS: We examined 20,207
      hypertensive participants with baseline and 2-year creatinine levels from which
      eGFR changes were estimated. The associations between eGFR change with incident
      coronary heart disease (CHD), stroke, heart failure (HF), all-cause mortality,
      and ESRD during 2.9 years of in-trial follow up, and with mortality during in
      trial and post-trial follow-up (7.6 years), were studied. Results were assessed
      by primary hypertension (HTN) treatment (chlorthalidone, lisinopril, and
      amlodipine) and adjusted for baseline eGFR levels. RESULTS: In the short run, an
      eGFR decline below the cohort median (-1.28 ml/minute/1.73 m2/2 years) vs. above
      the median, or a 5 ml/min/1.73 m2/year decline vs. no decline, was associated
      with significant hazard risk for CHD (1.06-1.28), HF (1.24-1.91), ESRD (2.84
      6.01), and mortality (1.08-1.19), but not with stroke risk. In the long term,
      there was a significant association with mortality (1.11-1.34). Interaction terms
      for outcomes by antihypertensive treatments were not statistically significant
      except for ESRD between amlodipine vs. chlorthalidone (hazard ratio: 3.17 [2.59,
      3.88] vs. 2.41 [1.98, 2.97]; P interaction = 0.005) for a 5 ml/min/1.73 m2/year
      eGFR decline. CONCLUSION: Decline in eGFR over 2 years is associated with
      increased risk of clinical outcomes beyond the effects of baseline eGFR. These
      risks were the same irrespective of the primary medication used to treat HTN.

PMID- 29360917
TI  - ESMO-MCBS v1.1: statistical and patient-relevant shortcomings.

PMID- 29360918
TI  - Effect of aperture number on pollen germination, survival and reproductive
      success in Arabidopsis thaliana.
AB  - Background and Aims: Pollen grains of flowering plants display a fascinating
      diversity of forms, including diverse patterns of apertures, the specialized
      areas on the pollen surface that commonly serve as the sites of pollen tube
      initiation and, therefore, might play a key role in reproduction. Although many
      aperture patterns exist in angiosperms, pollen with three apertures
      (triaperturate) constitutes the predominant pollen type found in eudicot species.
      The aim of this study was to explore whether having three apertures provides
      selective advantages over other aperture patterns in terms of pollen survival,
      germination and reproductive success, which could potentially explain the
      prevalence of triaperturate pollen among eudicots. Methods: The in vivo pollen
      germination, pollen tube growth, longevity and competitive ability to sire seeds
      were compared among pollen grains of Arabidopsis thaliana with different aperture
      numbers. For this, an arabidopsis pollen aperture series was used, which included
      the triaperturate wild type, as well as mutants without an aperture
      (inaperturate) and with more than three apertures. Key Results: Aperture number
      appears to influence pollen grain performance. In most germination and longevity
      experiments, the triaperturate and inaperturate pollen grains performed better
      than pollen with higher aperture numbers. In mixed pollinations, in which
      triaperturate and inaperturate pollen were forced to compete with each other, the
      triaperturate pollen outperformed the inaperturate pollen. Conclusions:
      Triaperturate pollen grains might provide the best trade-off among various pollen
      performance traits, thus explaining the prevalence of this morphological trait in
      the eudicot clade.

PMID- 29360919
TI  - Genomic medicine France 2025.

PMID- 29360920
TI  - EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1
      cream as prophylaxis for cetuximab-induced skin toxicity.
AB  - Background: Acne-like skin rash is a frequently occurring adverse event
      associated with drugs against the epidermal growth factor receptor. This
      randomized vehicle-controlled study investigated the addition of vitamin K1 cream
      to doxycycline in patients with metastatic colorectal cancer treated with
      cetuximab. Patients and methods: Patients receiving first-line cetuximab +
      FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and
      vitamin K1 cream or doxycycline and the vehicle. The primary end point of the
      study was the incidence of grade >= 2 skin rash (NCI CTCAE version 4.02) during 8
      weeks of skin treatment. Secondary end points comprised skin rash according to a
      more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy,
      and compliance. The study had 80% power to show a 20% reduction of the incidence
      of grade >= 2 skin rash. Results: A total of 126 patients were analyzed. The
      incidence of skin rash grade >= 2 was comparable between the arms. Likewise, no
      difference was seen in the WoMo score with respect to the percentage of skin
      affected. However, starting in week 5 and increasing over time patients treated
      with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as
      well as efficacy and compliance with study medication and anticancer treatment
      was comparable in both arms. Conclusion: The primary end point of decreasing
      grade >= 2 skin rash was not met. However, using vitamin K1 cream as part of
      prophylactic treatment decreased the severity of acne-like skin rash according to
      WoMo, an alternative and more thorough skin toxicity scoring tool.

PMID- 29360921
TI  - Recommendations for the clinical management of the elderly patient with malignant
      lymphoma.

PMID- 29360922
TI  - Salvage of Implant-Based Breast Reconstruction in Nipple-Sparing Mastectomies
      With Autologous Flaps.
AB  - Background: Implant-based breast reconstruction (IBR) after nipple-sparing
      mastectomies (NSM) can have complications that require explantation of a tissue
      expander or permanent prosthesis. When complications occur, preservation of the
      nipple-areola complex (NAC) remains critical to ensure aesthetic breast
      reconstruction. To date, there are minimal data on outcomes for patients
      experiencing unplanned explantations in IBR after NSM. Objectives: To evaluate
      final reconstructive outcomes for NSM patients who undergo IBR and have an
      unplanned explanation and to separately analyze the outcome of the NAC aesthetic
      subunit. Methods: We analyzed a prospectively maintained database of NSM patients
      undergoing IBR reconstruction at a single institution to identify patients who
      had complications resulting in unplanned explanation. Demographics, covariates,
      and reconstructive outcomes, including salvage with IBR or autologous flaps, were
      assessed. Final outcomes of the NAC were also evaluated. Results: A total of 213
      patients underwent 382 NSM with IBR with either direct-to-implant (DTI) or tissue
      expander/implant (TE/I) reconstructions. The complication rate was 15.2% (N = 58)
      and 33 (8.6%) unplanned explantations occurred: 23 (69.8%) of whom ultimately
      completed reconstruction with either IBR (30.4%) or autologous flaps (69.6%).
      NACs were preserved in 62.5% of breasts with unplanned explantations. Only 8 NACs
      were lost in the entire cohort (2.1%). Conclusions: Following unplanned
      explantations in IBR after NSM, salvage can be performed with either IBR or
      autologous flaps. However, the majority of salvage procedures in IBR after NSM
      will be with autologous flaps that bring in healthy soft tissue to restore
      location specific defects caused by complications. The NAC can ultimately be
      preserved as an aesthetic subunit in most patients despite the occurrence of
      initial complications. Level of Evidence 4: 

PMID- 29360923
TI  - First report of overall survival for ipilimumab plus nivolumab from the phase III
      Checkmate 067 study in advanced melanoma.

PMID- 29360924
TI  - Neopepsee: accurate genome-level prediction of neoantigens by harnessing sequence
      and amino acid immunogenicity information.
AB  - Background: Tumor-specific mutations form novel immunogenic peptides called
      neoantigens. Neoantigens can be used as a biomarker predicting patient response
      to cancer immunotherapy. Although a predicted binding affinity (IC50) between
      peptide and major histocompatibility complex class I is currently used for
      neoantigen prediction, large number of false-positives exist. Materials and
      methods: We developed Neopepsee, a machine-learning-based neoantigen prediction
      program for next-generation sequencing data. With raw RNA-seq data and a list of
      somatic mutations, Neopepsee automatically extracts mutated peptide sequences and
      gene expression levels. We tested 14 immunogenicity features to construct a
      machine-learning classifier and compared with the conventional methods based on
      IC50 regarding sensitivity and specificity. We tested Neopepsee on independent
      datasets from melanoma, leukemia, and stomach cancer. Results: Nine of the 14
      immunogenicity features that are informative and inter-independent were used to
      construct the machine-learning classifiers. Neopepsee provides a rich annotation
      of candidate peptides with 87 immunogenicity-related values, including IC50,
      expression levels of neopeptides and immune regulatory genes (e.g. PD1, PD-L1),
      matched epitope sequences, and a three-level (high, medium, and low) call for
      neoantigen probability. Compared with the conventional methods, the performance
      was improved in sensitivity and especially two- to threefold in the specificity.
      Tests with validated datasets and independently proven neoantigens confirmed the
      improved performance in melanoma and chronic lymphocytic leukemia. Additionally,
      we found sequence similarity in proteins to known pathogenic epitopes to be a
      novel feature in classification. Application of Neopepsee to 224 public stomach
      adenocarcinoma datasets predicted ~7 neoantigens per patient, the burden of which
      was correlated with patient prognosis. Conclusions: Neopepsee can detect
      neoantigen candidates with less false positives and be used to determine the
      prognosis of the patient. We expect that retrieval of neoantigen sequences with
      Neopepsee will help advance research on next-generation cancer immunotherapies,
      predictive biomarkers, and personalized cancer vaccines.

PMID- 29360925
TI  - Recurrent hyperactive ESR1 fusion proteins in endocrine therapy-resistant breast
      cancer.
AB  - Background: Estrogen receptor-positive (ER-positive) metastatic breast cancer is
      often intractable due to endocrine therapy resistance. Although ESR1 promoter
      switching events have been associated with endocrine-therapy resistance,
      recurrent ESR1 fusion proteins have yet to be identified in advanced breast
      cancer. Patients and methods: To identify genomic structural rearrangements (REs)
      including gene fusions in acquired resistance, we undertook a multimodal
      sequencing effort in three breast cancer patient cohorts: (i) mate-pair and/or
      RNAseq in 6 patient-matched primary-metastatic tumors and 51 metastases, (ii)
      high coverage (>500*) comprehensive genomic profiling of 287-395 cancer-related
      genes across 9542 solid tumors (5216 from metastatic disease), and (iii) ultra
      high coverage (>5000*) genomic profiling of 62 cancer-related genes in 254 ctDNA
      samples. In addition to traditional gene fusion detection methods (i.e.
      discordant reads, split reads), ESR1 REs were detected from targeted sequencing
      data by applying a novel algorithm (copyshift) that identifies major copy number
      shifts at rearrangement hotspots. Results: We identify 88 ESR1 REs across 83
      unique patients with direct confirmation of 9 ESR1 fusion proteins (including 2
      via immunoblot). ESR1 REs are highly enriched in ER-positive, metastatic disease
      and co-occur with known ESR1 missense alterations, suggestive of polyclonal
      resistance. Importantly, all fusions result from a breakpoint in or near ESR1
      intron 6 and therefore lack an intact ligand binding domain (LBD). In vitro
      characterization of three fusions reveals ligand-independence and hyperactivity
      dependent upon the 3' partner gene. Our lower-bound estimate of ESR1 fusions is
      at least 1% of metastatic solid breast cancers, the prevalence in ctDNA is at
      least 10* enriched. We postulate this enrichment may represent secondary
      resistance to more aggressive endocrine therapies applied to patients with ESR1
      LBD missense alterations. Conclusions: Collectively, these data indicate that N
      terminal ESR1 fusions involving exons 6-7 are a recurrent driver of endocrine
      therapy resistance and are impervious to ER-targeted therapies.

PMID- 29360926
TI  - OPAL: prediction of MoRF regions in intrinsically disordered protein sequences.
AB  - Motivation: Intrinsically disordered proteins lack stable 3-dimensional structure
      and play a crucial role in performing various biological functions. Key to their
      biological function are the molecular recognition features (MoRFs) located within
      long disordered regions. Computationally identifying these MoRFs from disordered
      protein sequences is a challenging task. In this study, we present a new MoRF
      predictor, OPAL, to identify MoRFs in disordered protein sequences. OPAL utilizes
      two independent sources of information computed using different component
      predictors. The scores are processed and combined using common averaging method.
      The first score is computed using a component MoRF predictor which utilizes
      composition and sequence similarity of MoRF and non-MoRF regions to detect MoRFs.
      The second score is calculated using half-sphere exposure (HSE), solvent
      accessible surface area (ASA) and backbone angle information of the disordered
      protein sequence, using information from the amino acid properties of flanks
      surrounding the MoRFs to distinguish MoRF and non-MoRF residues. Results: OPAL is
      evaluated using test sets that were previously used to evaluate MoRF predictors,
      MoRFpred, MoRFchibi and MoRFchibi-web. The results demonstrate that OPAL
      outperforms all the available MoRF predictors and is the most accurate predictor
      available for MoRF prediction. It is available at http://www.alok-ai
      lab.com/tools/opal/. Contact: ashwini@hgc.jp or alok.sharma@griffith.edu.au.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29360927
TI  - PhenoRank: reducing study bias in gene prioritization through simulation.
AB  - Motivation: Genome-wide association studies have identified thousands of loci
      associated with human disease, but identifying the causal genes at these loci is
      often difficult. Several methods prioritize genes most likely to be disease
      causing through the integration of biological data, including protein-protein
      interaction and phenotypic data. Data availability is not the same for all genes
      however, potentially influencing the performance of these methods. Results: We
      demonstrate that whilst disease genes tend to be associated with greater numbers
      of data, this may be at least partially a result of them being better studied.
      With this observation we develop PhenoRank, which prioritizes disease genes
      whilst avoiding being biased towards genes with more available data. Bias is
      avoided by comparing gene scores generated for the query disease against gene
      scores generated using simulated sets of phenotype terms, which ensures that
      differences in data availability do not affect the ranking of genes. We
      demonstrate that whilst existing prioritization methods are biased by data
      availability, PhenoRank is not similarly biased. Avoiding this bias allows
      PhenoRank to effectively prioritize genes with fewer available data and improves
      its overall performance. PhenoRank outperforms three available prioritization
      methods in cross-validation (PhenoRank area under receiver operating
      characteristic curve [AUC]=0.89, DADA AUC = 0.87, EXOMISER AUC = 0.71, PRINCE AUC
      = 0.83, P < 2.2 * 10-16). Availability and implementation: PhenoRank is freely
      available for download at https://github.com/alexjcornish/PhenoRank.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29360928
TI  - APAtrap: identification and quantification of alternative polyadenylation sites
      from RNA-seq data.
AB  - Motivation: Alternative polyadenylation (APA) has been increasingly recognized as
      a crucial mechanism that contributes to transcriptome diversity and gene
      expression regulation. As RNA-seq has become a routine protocol for transcriptome
      analysis, it is of great interest to leverage such unprecedented collection of
      RNA-seq data by new computational methods to extract and quantify APA dynamics in
      these transcriptomes. However, research progress in this area has been relatively
      limited. Conventional methods rely on either transcript assembly to determine
      transcript 3' ends or annotated poly(A) sites. Moreover, they can neither
      identify more than two poly(A) sites in a gene nor detect dynamic APA site usage
      considering more than two poly(A) sites. Results: We developed an approach called
      APAtrap based on the mean squared error model to identify and quantify APA sites
      from RNA-seq data. APAtrap is capable of identifying novel 3' UTRs and 3' UTR
      extensions, which contributes to locating potential poly(A) sites in previously
      overlooked regions and improving genome annotations. APAtrap also aims to tally
      all potential poly(A) sites and detect genes with differential APA site usages
      between conditions. Extensive comparisons of APAtrap with two other latest
      methods, ChangePoint and DaPars, using various RNA-seq datasets from simulation
      studies, human and Arabidopsis demonstrate the efficacy and flexibility of
      APAtrap for any organisms with an annotated genome. Availability and
      implementation: Freely available for download at https://apatrap.sourceforge.io.
      Contact: liqq@xmu.edu.cn or xhuister@xmu.edu.cn. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29360929
TI  - ST Spot Detector: a web-based application for automatic spot and tissue detection
      for spatial Transcriptomics image datasets.
AB  - Motiviation: Spatial Transcriptomics (ST) is a method which combines high
      resolution tissue imaging with high troughput transcriptome sequencing data. This
      data must be aligned with the images for correct visualization, a process that
      involves several manual steps. Results: Here we present ST Spot Detector, a web
      tool that automates and facilitates this alignment through a user friendly
      interface. Contact: jose.fernandez.navarro@scilifelab.se. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29360930
TI  - ADEPTUS: a discovery tool for disease prediction, enrichment and network analysis
      based on profiles from many diseases.
AB  - Motivation: Large-scale publicly available genomic data on many disease
      phenotypes could improve our understanding of the molecular basis of disease.
      Tools that undertake this challenge by jointly analyzing multiple phenotypes are
      needed. Results: ADEPTUS is a web-tool that enables various functional genomics
      analyses based on a high-quality curated database spanning >38, 000 gene
      expression profiles and >100 diseases. It offers four types of analysis. (i) For
      a gene list provided by the user it computes disease ontology (DO), pathway, and
      gene ontology (GO) enrichment and displays the genes as a network. (ii) For a
      given disease, it enables exploration of drug repurposing by creating a gene
      network summarizing the genomic events in it. (iii) For a gene of interest, it
      generates a report summarizing its behavior across several studies. (iv) It can
      predict the tissue of origin and the disease of a sample based on its gene
      expression or its somatic mutation profile. Such analyses open novel ways to
      understand new datasets and to predict primary site of cancer. Availability and
      implementation: Data and tool: http://adeptus.cs.tau.ac.il/home Analyses:
      Supplementary Material. Contact: rshamir@tau.ac.il. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29360931
TI  - Diel pattern of floral scent emission matches the relative importance of diurnal
      and nocturnal pollinators in populations of Gymnadenia conopsea.
AB  - Background and Aims: Floral scent is considered an integral component of
      pollination syndromes, and its composition and timing of emission are thus
      expected to match the main pollinator type and time of activity. While floral
      scent differences among plant species with different pollination systems can be
      striking, studies on intraspecific variation are sparse, which limits our
      understanding of the role of pollinators in driving scent divergence. Methods:
      Here, we used dynamic headspace sampling to quantify floral scent emission and
      composition during the day and at night in the natural habitat of six
      Scandinavian populations of the fragrant orchid Gymnadenia conopsea. We tested
      whether diel scent emission and composition match pollinator type by comparing
      four populations in southern Sweden, where nocturnal pollinators are more
      important for plant reproductive success than are diurnal pollinators, with two
      populations in central Norway, where the opposite is true. To determine to what
      extent scent patterns quantified in the field reflected plasticity, we also
      measured scent emission in a common growth chamber environment. Key Results: Both
      scent composition and emission rates differed markedly between day and night, but
      only the latter varied significantly among populations. The increase in scent
      emission rate at night was considerably stronger in the Swedish populations
      compared with the Norwegian populations. These patterns persisted when plants
      were transferred to a common environment, suggesting a genetic underpinning of
      the scent variation. Conclusions: The results are consistent with a scenario
      where spatial variation in relative importance of nocturnal and diurnal
      pollinators has resulted in selection for different scent emission rhythms. Our
      study highlights the importance of adding a characterization of diel variation of
      scent emission rates to comparative studies of floral scent, which so far have
      often focused on scent composition only.

PMID- 29360933
TI  - DExSI: a new tool for the rapid quantitation of 13C-labelled metabolites detected
      by GC-MS.
AB  - Summary: Stable isotope directed metabolomics is increasingly being used to
      measure metabolic fluxes in microbial, plant and animal cells. Incorporation of
      13C/15N isotopes into a wide range of metabolites is typically determined using
      gas chromatography-mass spectrometry (GC/MS) or other hyphenated mass
      spectrometry approaches. The DExSI (Data Extraction for Stable Isotope-labelled
      metabolites) pipeline is an interactive graphical software package which can be
      used to rapidly quantitate isotopologues for a wide variety of metabolites
      detected by GC/MS. DExSI performs automated metabolite annotation, mass and
      positional isotopomer abundance determination and natural isotope abundance
      correction. It provides a range of output options and is suitable for high
      throughput analyses. Availability and implementation: DExSI is available for non
      commercial use from: https://github.com/DExSI/DExSI/. For Microsoft Windows 7 or
      higher (64-bit). Contact: malcolmm@unimelb.edu.au or
      michael.dagley@unimelb.edu.au. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29360932
TI  - Impact of palbociclib plus letrozole on patient-reported health-related quality
      of life: results from the PALOMA-2 trial.
AB  - Background: Patient-reported outcomes are integral in benefit-risk assessments of
      new treatment regimens. The PALOMA-2 study provides the largest body of evidence
      for patient-reported health-related quality of life (QOL) for patients with
      metastatic breast cancer (MBC) receiving first-line endocrine-based therapy
      (palbociclib plus letrozole and letrozole alone). Patients and methods: Treatment
      naive postmenopausal women with estrogen receptor-positive (ER+)/human epidermal
      growth factor receptor 2-negative (HER2-) MBC were randomized 2 : 1 to
      palbociclib plus letrozole (n = 444) or placebo plus letrozole (n = 222). Patient
      reported outcomes were assessed at baseline, day 1 of cycles 2 and 3, and day 1
      of every other cycle from cycle 5 using the Functional Assessment of Cancer
      Therapy (FACT)-Breast and EuroQOL 5 dimensions (EQ-5D) questionnaires. Results:
      As of 26 February 2016, the median duration of follow-up was 23 months. Baseline
      scores were comparable between the two treatment arms. No significant between-arm
      differences were observed in change from baseline in FACT-Breast Total, FACT
      General Total, or EQ-5D scores. Significantly greater improvement in pain scores
      was observed in the palbociclib plus letrozole arm (-0.256 versus -0.098; P =
      0.0183). In both arms, deterioration of FACT-Breast Total score was significantly
      delayed in patients without progression versus those with progression and
      patients with partial or complete response versus those without. No significant
      difference was observed in FACT-Breast and EQ-5D index scores in patients with
      and without neutropenia. Conclusions: Overall, women with MBC receiving first
      line endocrine therapy have a good QOL. The addition of palbociclib to letrozole
      maintains health-related QOL and improves pain scores in treatment-naive
      postmenopausal patients with ER+/HER2- MBC compared with letrozole alone.
      Significantly greater delay in deterioration of health-related QOL was observed
      in patients without progression versus those who progressed and in patients with
      an objective response versus non-responders. ClinicalTrials.gov: NCT01740427
      (https://clinicaltrials.gov/ct2/show/NCT01740427).

PMID- 29360934
TI  - Application of a Porous Polyethylene Spreader Graft for Nasal Lengthening in
      Asian Patients.
AB  - Background: Rhinoplasty maneuvers to lengthen the nose include placing an
      alloplastic implant, caudally rotating the lower lateral cartilage (LLC), and
      stretching the soft tissue skin envelope (STSE) downward. Tissue tension
      associated with these procedures can result in implant extrusion or tip
      retraction. Objectives: The authors performed rhinoplasty with implantation of
      porous polyethylene (Medpor). The Medpor device enabled transfer of tension from
      the LLC and STSE to the juncture of the septal cartilage and upper lateral
      cartilage (ULC), thereby stabilizing the nasal structures. Methods: Twenty-six
      patients who underwent rhinoplasty with nasal augmentation and lengthening were
      evaluated in a prospective study. Two pieces of Medpor were placed as a spreader
      graft, and a third piece was inserted as a columellar strut. The released LLC was
      rotated caudally, and the domal segments were wrapped over the caudally projected
      tip of the implant. Surgical outcomes were assessed with a patient satisfaction
      questionnaire and by photogrammetry. Results: Patients were monitored for an
      average of 9.6 months. The patients' mean nasolabial angle (NLA) was 106.2
      degrees  +/- 4.7 degrees  preoperatively and 94.3 degrees  +/- 3.7 degrees 
      postoperatively (t < 0.0001). Most patients were fairly or completely satisfied
      with the operative outcome. One patient had impending implant extrusion and
      underwent explanation. Conclusions: Medpor material is easy to shape and is
      sufficiently strong to function as a spreader graft and withstand the tension
      associated with repositioning of the LLC and STSE. Level of Evidence 4: 

PMID- 29360935
TI  - A Systematic Review and Meta-analysis of the Factors Associated With Nonadherence
      and Discontinuation of Statins Among People Aged >=65 Years.
AB  - Background: Older individuals (aged >=65 years) are commonly prescribed statins
      but may experience a range of barriers in adhering to therapy. The factors
      associated with poor statin adherence and/or discontinuation among this
      population have not been comprehensively reviewed. Methods: We conducted a
      systematic review to identify English articles published through December 12,
      2016 that reported factors associated with nonadherence and/or discontinuation of
      statins among older persons. Data were pooled via random-effects meta-analysis
      techniques. Results: Forty-five articles reporting data from more than 1.8
      million older statin users from 13 countries were included. The factors
      associated with increased statin nonadherence were black/non-white race (odds
      ratio [OR] 1.66, 95% confidence interval [CI] 1.39-1.98), female gender (OR 1.08,
      95% CI 1.03-1.13), current smoker (OR 1.12, 95% CI 1.03-1.21), higher copayments
      (OR 1.38, 95% CI 1.25-1.52), new user (OR 1.58, 95% CI 1.21-2.07), lower number
      of concurrent cardiovascular medications (OR 1.08, 95% CI 1.06-1.09), primary
      prevention (OR 1.49, 95% CI 1.40-1.59), having respiratory disorders (OR 1.17,
      95% CI 1.12-1.23) or depression (OR 1.11, 95% CI 1.06-1.16), and not having renal
      disease (OR 1.09, 95% CI 1.04-1.14). The factors associated with increased statin
      discontinuation were lower income status (OR 1.20, 95% CI 1.06-1.36), current
      smoker (OR 1.14, 95% CI 1.06-1.23), higher copayment (OR 1.61, 95% CI 1.53-1.70),
      higher number of medications (OR 1.04, 95% CI 1.01-1.06), presence of dementia
      (OR 1.18, 95% CI 1.02-1.36), cancer (OR 1.22, 95% CI 1.11-1.33) or respiratory
      disorders (OR 1.19, 95% CI 1.05-1.34), primary prevention (OR 1.66, 95% CI 1.24
      2.22), and not having hypertension (OR 1.13, 95% CI 1.07-1.20) or diabetes (OR
      1.09, 95% CI 1.04-1.15). Conclusion: Interventions that target potentially
      modifiable factors including financial and social barriers, patients' perceptions
      about disease risk as well as polypharmacy may improve statin use in the older
      population.

PMID- 29360936
TI  - Haystack: systematic analysis of the variation of epigenetic states and cell-type
      specific regulatory elements.
AB  - Motivation: With the increasing amount of genomic and epigenomic data in the
      public domain, a pressing challenge is to integrate these data to investigate the
      role of epigenetic mechanisms in regulating gene expression and maintenance of
      cell-identity. To this end, we have implemented a computational pipeline to
      systematically study epigenetic variability and uncover regulatory DNA sequences.
      Results: Haystack is a bioinformatics pipeline to identify hotspots of epigenetic
      variability across different cell-types, cell-type specific cis-regulatory
      elements, and associated transcription factors. Haystack is generally applicable
      to any epigenetic mark and provides an important tool to investigate the
      mechanisms underlying epigenetic switches during development. This software is
      accompanied by a set of precomputed tracks, which may be used as a valuable
      resource for functional annotation of the human genome. Availability and
      implementation: The Haystack pipeline is implemented as an open-source,
      multiplatform, Python package called haystack_bio freely available at
      https://github.com/pinellolab/haystack_bio. Contact: lpinello@mgh.harvard.edu or
      gcyuan@jimmy.harvard.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29360937
TI  - Reply to Yamamoto and Nishimura.

PMID- 29360938
TI  - Long-term Persistent Organic Pollutants Exposure Induced Telomere Dysfunction and
      Senescence-Associated Secretary Phenotype.
AB  - Environmentally persistent organic pollutant (POP) is the general term for
      refractory organic compounds that show long-range atmospheric transport,
      environmental persistence, and bioaccumulation. It has been reported that the
      accumulation of POPs could lead to cellular DNA damage and adverse effects of on
      metabolic health. To better understand the mechanism of the health risks
      associated with POPs, we conducted an evidence-based cohort investigation (n =
      5,955) at the Jinghai e-waste disposal center in China from 2009 to 2016, where
      people endure serious POP exposure. And high levels of aging-related diseases,
      including hypertension, diabetes, autoimmune diseases, and reproductive disorders
      were identified associated with the POP exposure. In the subsequent molecular
      level study, an increased telomere dysfunction including telomere multiple
      telomere signals, telomere signal-free ends, telomere shortening and activation
      of alternative lengthening of telomeres were observed, which might result from
      the hypomethylated DNA modification induced telomeric repeat-containing RNA
      overexpression. Moreover, dysfunctional telomere-leaded senescence-associated
      secretory phenotype was confirmed, as the proinflammatory cytokines and
      immunosenescence hallmarks including interleukin-6, P16INK4a, and P14ARF were
      stimulated. Thus, we proposed that the dysfunctional telomere and elevated
      systemic chronic inflammation contribute to the aging-associated diseases, which
      were highly developed among the POP exposure individuals.

PMID- 29360939
TI  - Strongyloidiasis Outside Endemic Areas: Long-term Parasitological and Clinical
      Follow-up After Ivermectin Treatment.
AB  - Background: Strongyloides stercoralis affects 30-100 million people worldwide.
      The first-line therapy is ivermectin. Cure is defined as the absence of larvae by
      parasitological methods 1 year after treatment. To date, no longitudinal
      parasitological studies for longer periods of time have been conducted to confirm
      its cure. Here, we evaluated treatment response in long-term follow-up patients
      with chronic infection using parasitological and molecular methods for larvae or
      DNA detection. Methods: A prospective, descriptive, observational study was
      conducted between January 2009 and September 2015 in Buenos Aires, Argentina.
      Twenty-one patients with S. stercoralis diagnosis were evaluated 30, 60, and 90
      days as well as 1, 2, 3, and/or 4 years after treatment by conventional methods
      (fresh stool, Ritchie method, agar plate culture), S. stercoralis-specific
      polymerase chain reaction (PCR) in stool DNA, and eosinophil values. Results:
      During follow-up, larvae were detected by conventional methods in 14 of 21
      patients. This parasitological reactivation was observed starting 30 days
      posttreatment (dpt) and then at different times since 90 dpt. Eosinophil values
      decreased (P = .001) 30 days after treatment, but their levels were neither
      associated with nor predicted these reactivations. However, S. stercoralis DNA
      was detected by PCR in all patients, both in their first and subsequent stool
      samples, thus reflecting the poor efficacy of ivermectin at eradicating parasite
      from host tissues. Asymptomatic eosinophilia was the most frequent clinical form
      among chronically infected patients. Conclusions: These results suggest that the
      parasitological cure is unlikely. Strongyloidiasis must be considered a chronic
      infection and ivermectin administration schedules should be reevaluated.

PMID- 29360940
TI  - From genetics to response to injury: vascular smooth muscle cells in aneurysms
      and dissections of the ascending aorta.
AB  - Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis
      of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and
      in the associated adaptive compensatory responses, since thrombosis and
      inflammatory processes are absent in the majority of cases. Aneurysms and
      dissections share numerous characteristics, including aetiologies and
      histopathological alterations: vSMC disappearance, medial areas of mucoid
      degeneration, and extracellular matrix (ECM) breakdown. Three aetiologies
      predominate in TAAD in humans: (i) genetic causes in heritable familial forms,
      (ii) an association with bicuspid aortic valves, and (iii) a sporadic
      degenerative form linked to the aortic aging process. Genetic forms include
      mutations in vSMC genes encoding for molecules of the ECM or the TGF-beta
      pathways, or participating in vSMC tone. On the other hand, aneurysms and
      dissections, whatever their aetiologies, are characterized by an increase in wall
      permeability leading to transmural advection of plasma proteins which could
      interact with vSMCs and ECM components. In this context, blood-borne plasminogen
      appears to play an important role, because its outward convection through the
      wall is increased in TAAD, and it could be converted to active plasmin at the
      vSMC membrane. Active plasmin can induce vSMC disappearance, proteolysis of
      adhesive proteins, activation of MMPs and release of TGF-beta from its ECM
      storage sites. Conversely, vSMCs could respond to aneurysmal biomechanical and
      proteolytic injury by an epigenetic phenotypic switch, including constitutional
      overexpression and nuclear translocation of Smad2 and an increase in antiprotease
      and ECM protein synthesis. In contrast, such an epigenetic phenomenon is not
      observed in dissections. In this context, dysfunction of proteins involved in
      vSMC tone are interesting to study, particularly in interaction with plasma
      protein transport through the wall and TGF-beta activation, to establish the
      relationship between these dysfunctions and ECM proteolysis.

PMID- 29360941
TI  - Utility of intracoronary imaging in the cardiac catheterization laboratory:
      comprehensive evaluation with intravascular ultrasound and optical coherence
      tomography.
AB  - Background: Intracoronary imaging is an important tool for guiding decision
      making in the cardiac catheterization laboratory. Sources of data: We have
      reviewed the latest available evidence in the field to highlight the various
      potential benefits of intravascular imaging. Areas of agreement: Coronary
      angiography has been considered the gold standard test to appropriately diagnose
      and manage patients with coronary artery disease, but it has the inherent
      limitation of being a 2-dimensional x-ray lumenogram of a complex 3-dimensional
      vascular structure. Areas of controversy: There is well-established inter- and
      intra-observer variability in reporting coronary angiograms leading to potential
      variability in various management strategies. Intracoronary imaging improves the
      diagnostic accuracy while optimizing the results of an intervention. Utilization
      of intracoronary imaging modalities in routine practice however remains low
      worldwide. Increased costs, resources, time and expertise have been cited as
      explanations for low incorporation of these techniques. Growing points:
      Intracoronary imaging supplements and enhances an operator's decision-making
      ability based on detailed and objective lesion assessment rather than a
      subjective visual estimation. The benefits of intravascular imaging are becoming
      more profound as the complexity of cases suitable for revascularization
      increases. Areas timely for developing research: While the clinical benefits of
      intravascular ultrasound have been well validated, optical coherence tomography
      in comparison is a newer technology, with robust clinical trials assessing its
      clinical benefit are underway.

PMID- 29360942
TI  - IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis.
AB  - Aims: An excess of aldosterone results in cardiac remodelling and fibrosis.
      Interleukin-6 (IL-6) is a key mediator in the fibrotic process; however, the
      effect of aldosterone on the expression of IL-6 remains unclear. We investigated
      whether aldosterone induces the expression of IL-6 and thereby contributes to the
      fibrotic process. Methods and results: In this clinical study, we prospectively
      enrolled 25 patients with primary aldosteronism (PA) and 26 patients with
      essential hypertension (EH). The PA patients had higher plasma IL-6 levels, left
      ventricular mass index, degree of myocardial fibrosis, and more impaired
      diastolic function than the EH patients. In addition, plasma IL-6 levels were
      positively correlated with 24-h urinary aldosterone and echocardiographic
      parameters. In cell studies, we investigated the possible molecular mechanism how
      aldosterone-induced IL-6 secretion and the further effects of collagen
      production. Aldosterone significantly induced IL-6 protein and mRNA production in
      human umbilical vein endothelial cells. Intracellular signalling occurred through
      the mineralocorticoid receptor/PI3K/Akt/NF-kB pathway. In cardiac fibroblasts, IL
      6 trans-signalling played a critical role in aldosterone-induced IL-6-enhanced
      fibrosis-related factor expression. To further investigate the role of IL-6 trans
      signalling in aldosterone-induced cardiac fibrosis, we measured the severity of
      myocardial fibrosis in aldosterone infusion mice models including an IL-6
      chemical inhibitor and Sgp130 Knockin Transgenic Mice. Mice receiving recombinant
      soluble gp130 and Sgp130 Knockin Transgenic Mice prevented myocardial fibrosis
      and cardiac hypertrophy by aldosterone infusion. Conclusions: IL-6 trans
      signalling contributes to aldosterone-induced cardiac fibrosis.

PMID- 29360943
TI  - Spike-related haemodynamic responses overlap with high frequency oscillations in
      patients with focal epilepsy.
AB  - Simultaneous scalp EEG/functional MRI measures non-invasively haemodynamic
      responses to interictal epileptic discharges, which are related to the
      epileptogenic zone. High frequency oscillations are also an excellent indicator
      of this zone, but are primarily recorded from intracerebral EEG. We studied the
      spatial overlap of these two important markers in patients with drug-resistant
      epilepsy to assess if their combination could help better define the extent of
      the epileptogenic zone. We included patients who underwent EEG-functional MRI and
      later intracerebral EEG. Based on intracerebral EEG findings, we separated
      patients with unifocal seizures from patients with multifocal or unknown onset
      seizures. Haemodynamic t-maps were coregistered with the intracerebral electrode
      positions. Each EEG channel was classified as pertaining to one of the following
      categories: primary haemodynamic cluster (maximum t-value), secondary cluster (t
      value > 90% of the primary cluster) or outside the primary and secondary
      clusters. We marked high frequency oscillations (ripples: 80-250 Hz; fast
      ripples: 250-500 Hz) during 1 h of slow wave sleep, and compared their rates in
      each haemodynamic category. After classifying channels as high- or low-rate, the
      proportion of high-rate channels within the primary or primary plus secondary
      clusters was compared to the proportion expected by chance. Twenty-five patients,
      11 with unifocal and 14 with multifocal/unknown seizure onsets, were studied. We
      found a significantly higher median high frequency oscillation rate in the
      primary cluster compared to secondary cluster and outside these two clusters for
      the unifocal group (P < 0.0001), but not for the multifocal/unknown group. For
      the unifocal group, the number of high-rate channels within the primary or
      primary plus secondary clusters was significantly higher than expected by chance.
      This held only for the high-ripple-rate channels in the multifocal/unknown group.
      At the patient level, most patients (18/25, or 72%) had at least one high-rate
      channel within a primary cluster. In patients with unifocal epilepsy, the maximum
      haemodynamic response (primary cluster) related to scalp interictal discharges
      overlaps with the tissue generating high frequency oscillations at high rates. If
      intracranial EEG is warranted, this response should be explored. As a tentative
      clinical use of the combination of these techniques we propose that higher high
      frequency oscillation rates inside than outside the maximum response indicates
      that the patient has indeed a focal epileptogenic zone demarcated by this
      response, whereas similar rates inside and outside may indicate a widespread
      epileptogenic zone or an epileptogenic zone not covered by the implantation.

PMID- 29360945
TI  - Electrical coupling between cardiomyocytes and fibroblasts: experimental testing
      of a challenging and important concept.

PMID- 29360944
TI  - Migraine with visual aura associated with thicker visual cortex.
AB  - Until recent years it was believed that migraine with aura was a disorder causing
      intermittent neurological symptoms, with no impact on brain structure. However,
      recent MRI studies have reported increased cortical thickness of visual and
      somatosensory areas in patients with migraine with aura, suggesting that such
      structural alterations were either due to increased neuronal density in the areas
      involved, or a result of multiple episodes of cortical spreading depression as
      part of aura attacks. Subsequent studies have yielded conflicting results,
      possibly due to methodological reasons, e.g. small number of subjects. In this
      cross-sectional study, we recruited females aged 30-60 years from the nationwide
      Danish Twin Registry. Brain MRI of females with migraine with aura (patients),
      their co-twins, and unrelated migraine-free twins (controls) were performed at a
      single centre and assessed for cortical thickness in predefined cortical areas
      (V1, V2, V3A, MT, somatosensory cortex), blinded to headache diagnoses. The
      difference in cortical thickness between patients and controls adjusted for age,
      and other potential confounders was assessed. Comparisons of twin pairs
      discordant for migraine with aura were also performed. Comparisons were based on
      166 patients, 30 co-twins, and 137 controls. Compared with controls, patients had
      a thicker cortex in areas V2 [adjusted mean difference 0.032 mm (95% confidence
      interval 0.003 to 0.061), V3A [adjusted mean difference 0.037 mm (95% confidence
      interval 0.008 to 0.067)], while differences in the remaining areas examined were
      not statistically significant [adjusted mean difference (95% confidence
      interval): V1 0.022 (-0.007 to 0.052); MT: 0.018 (-0.011 to 0.047); somatosensory
      cortex: 0.020 (-0.009 to 0.049)]. We found no association between the regions of
      interest and active migraine, or number of lifetime aura attacks. Migraine with
      aura discordant twin pairs (n = 30) only differed in mean thickness of V2 (0.039
      mm, 95% CI 0.005 to 0.074). In conclusion, females with migraine with aura have a
      thicker cortex corresponding to visual areas and our results indicate this may be
      an inherent trait rather than a result of repeated aura attacks.

PMID- 29360946
TI  - Nonparametric Bayesian inference for mean residual life functions in survival
      analysis.
AB  - Modeling and inference for survival analysis problems typically revolves around
      different functions related to the survival distribution. Here, we focus on the
      mean residual life (MRL) function, which provides the expected remaining lifetime
      given that a subject has survived (i.e. is event-free) up to a particular time.
      This function is of direct interest in reliability, medical, and actuarial
      fields. In addition to its practical interpretation, the MRL function
      characterizes the survival distribution. We develop general Bayesian
      nonparametric inference for MRL functions built from a Dirichlet process mixture
      model for the associated survival distribution. The resulting model for the MRL
      function admits a representation as a mixture of the kernel MRL functions with
      time-dependent mixture weights. This model structure allows for a wide range of
      shapes for the MRL function. Particular emphasis is placed on the selection of
      the mixture kernel, taken to be a gamma distribution, to obtain desirable
      properties for the MRL function arising from the mixture model. The inference
      method is illustrated with a data set of two experimental groups and a data set
      involving right censoring. The supplementary material available at Biostatistics
      online provides further results on empirical performance of the model, using
      simulated data examples.

PMID- 29360948
TI  - Diet-induced obesity alters the maternal metabolome and early placenta
      transcriptome and decreases placenta vascularity in the mouse.
AB  - Maternal obesity is associated with an increased risk of obesity and metabolic
      disease in offspring. Increasing evidence suggests that the placenta plays an
      active role in fetal programming. In this study, we used a mouse model of diet
      induced obesity to demonstrate that the abnormal metabolic milieu of maternal
      obesity sets the stage very early in pregnancy by altering the transcriptome of
      placenta progenitor cells in the preimplantation (trophectoderm [TE]) and early
      postimplantation (ectoplacental cone [EPC]) placenta precursors, which is
      associated with later changes in placenta development and function. Sphingolipid
      metabolism was markedly altered in the plasma of obese dams very early in
      pregnancy as was expression of genes related to sphingolipid processing in the
      early placenta. Upregulation of these pathways inhibits angiogenesis and causes
      endothelial dysfunction. The expression of many other genes related to
      angiogenesis and vascular development were disrupted in the TE and EPC. Other key
      changes in the maternal metabolome in obese dams that are likely to influence
      placenta and fetal development include a marked decrease in myo and chiro
      inositol. These early metabolic and gene expression changes may contribute to
      phenotypic changes in the placenta, as we found that exposure to a high-fat diet
      decreased placenta microvessel density at both mid and late gestation. This is
      the first study to demonstrate that maternal obesity alters the transcriptome at
      the earliest stages of murine placenta development.

PMID- 29360947
TI  - Anatomy of aphasia revisited.
AB  - In most cases, aphasia is caused by strokes involving the left hemisphere, with
      more extensive damage typically being associated with more severe aphasia. The
      classical model of aphasia commonly adhered to in the Western world is the
      Wernicke-Lichtheim model. The model has been in existence for over a century, and
      classification of aphasic symptomatology continues to rely on it. However, far
      more detailed models of speech and language localization in the brain have been
      formulated. In this regard, the dual stream model of cortical brain organization
      proposed by Hickok and Poeppel is particularly influential. Their model describes
      two processing routes, a dorsal stream and a ventral stream, that roughly support
      speech production and speech comprehension, respectively, in normal subjects.
      Despite the strong influence of the dual stream model in current
      neuropsychological research, there has been relatively limited focus on
      explaining aphasic symptoms in the context of this model. Given that the dual
      stream model represents a more nuanced picture of cortical speech and language
      organization, cortical damage that causes aphasic impairment should map clearly
      onto the dual processing streams. Here, we present a follow-up study to our
      previous work that used lesion data to reveal the anatomical boundaries of the
      dorsal and ventral streams supporting speech and language processing.
      Specifically, by emphasizing clinical measures, we examine the effect of cortical
      damage and disconnection involving the dorsal and ventral streams on aphasic
      impairment. The results reveal that measures of motor speech impairment mostly
      involve damage to the dorsal stream, whereas measures of impaired speech
      comprehension are more strongly associated with ventral stream involvement.
      Equally important, many clinical tests that target behaviours such as naming,
      speech repetition, or grammatical processing rely on interactions between the two
      streams. This latter finding explains why patients with seemingly disparate
      lesion locations often experience similar impairments on given subtests. Namely,
      these individuals' cortical damage, although dissimilar, affects a broad cortical
      network that plays a role in carrying out a given speech or language task. The
      current data suggest this is a more accurate characterization than ascribing
      specific lesion locations as responsible for specific language
      deficits.awx363media15705668782001.

PMID- 29360949
TI  - Dopaminergic abnormalities following traumatic brain injury.
AB  - Traumatic brain injury can reduce striatal dopamine levels. The cause of this is
      uncertain, but is likely to be related to damage to the nigrostriatal system. We
      investigated the pattern of striatal dopamine abnormalities using 123I-Ioflupane
      single-photon emission computed tomography (SPECT) scans and their relationship
      to nigrostriatal damage and clinical features. We studied 42 moderate-severe
      traumatic brain injury patients with cognitive impairments but no motor
      parkinsonism signs and 20 healthy controls. 123I-Ioflupane scanning was used to
      assess dopamine transporter levels. Clinical scan reports were compared to
      quantitative dopamine transporter results. Advanced MRI methods were used to
      assess the nigrostriatal system, including the area through which the
      nigrostriatal projections pass as defined from high-resolution Human Connectome
      data. Detailed clinical and neuropsychological assessments were performed. Around
      20% of our moderate-severe patients had clear evidence of reduced specific
      binding ratios for the dopamine transporter in the striatum measured using 123I
      Ioflupane SPECT. The caudate was affected more consistently than other striatal
      regions. Dopamine transporter abnormalities were associated with reduced
      substantia nigra volume. In addition, diffusion MRI provided evidence of damage
      to the regions through which the nigrostriatal tract passes, particularly the
      area traversed by dopaminergic projections to the caudate. Only a small
      percentage of patients had evidence of macroscopic lesions in the striatum and
      there was no relationship between presence of lesions and dopamine transporter
      specific binding ratio abnormalities. There was also no relationship between
      reduced volume in the striatal subregions and reduced dopamine transporter
      specific binding ratios. Patients with low caudate dopamine transporter specific
      binding ratios show impaired processing speed and executive dysfunction compared
      to patients with normal levels. Taken together, our results suggest that the
      dopaminergic system is affected by a moderate-severe traumatic brain injury in a
      significant proportion of patients, even in the absence of clinical motor
      parkinsonism. Reduced dopamine transporter levels are most commonly seen in the
      caudate and this is likely to reflect the pattern of nigrostriatal tract damage
      produced by axonal injury and associated midbrain damage.

PMID- 29360951
TI  - Too Much Optimism in the HANDOC Score.

PMID- 29360950
TI  - Attributable Healthcare Resource Utilization and Costs for Patients With Primary
      and Recurrent Clostridium difficile Infection in the United States.
AB  - Background: The economic burden of Clostridium difficile infection (CDI), the
      leading cause of nosocomial infectious diarrhea, is not well understood. The
      objective of this study was to estimate the healthcare resource utilization
      (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). Methods:
      This is a database (MarketScan) study. Patients without CDI were matched 1:1 by
      propensity score to those with primary CDI but no recurrences to obtain HCRU and
      costs attributable to primary CDI. Patients with primary CDI but no recurrences
      were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence
      in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for
      incremental cumulative hospitalized days and healthcare costs over a 6-month
      follow-up period were obtained by generalized linear models with a Poisson or
      gamma distribution and a log link. Bootstrapping was used to obtain 95%
      confidence intervals (CIs). Results: A total of 55504 eligible CDI patients were
      identified. Approximately 25% of these CDI patients had rCDI. The cumulative
      hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up
      period were 5.20 days (95% CI, 5.01-5.39) and 1.95 days (95% CI, 1.48-2.43),
      respectively. The healthcare costs attributable to primary CDI and rCDI over the
      6-month follow-up period were $24205 (95% CI, $23436-$25013) and $10580 (95% CI,
      $8849-$12446), respectively. Conclusions: The HCRU and costs attributable to
      primary CDI and rCDI are quite substantial. It is necessary to reduce the burden
      of CDI, especially rCDI.

PMID- 29360952
TI  - Loss of KCNK3 is a hallmark of RV hypertrophy/dysfunction associated with
      pulmonary hypertension.
AB  - Aims: Mutations in the KCNK3 gene, which encodes for an outward-rectifier K+
      channel, have been identified in patients suffering from pulmonary arterial
      hypertension (PAH), and constitute the first described channelopathy in PAH. In
      human PAH and experimental pulmonary hypertension (PH), we demonstrated that
      KCNK3 expression and function are severely reduced in pulmonary vascular cells,
      promoting PH-like phenotype at the morphologic and haemodynamic levels. Since
      KCNK3 channel is also expressed in both the human and rodent heart, we aimed to
      elucidate the pathophysiological role of KCNK3 channel in right ventricular (RV)
      hypertrophy (RVH) related to PH. Methods and results: Using whole-cell Patch
      clamp technique, we demonstrated that KCNK3 is predominantly expressed in adult
      rat RV cardiomyocytes compared to the left ventricle cardiomyocytes and
      participates in the repolarizing phase of the RV action potential. We revealed a
      reduction in KCNK3 function prior to development of RVH and the rise of pulmonary
      vascular resistance. KCNK3 function is severely reduced in RV cardiomyocytes
      during the development of RVH in several rat models of PH (exposure to
      monocrotaline, chronic hypoxia, and Sugen/hypoxia) and chronic RV pressure
      overload (pulmonary artery banding). In experimental PH, we revealed a reduction
      in KCNK3 function before any rise in pulmonary vascular resistance and the
      development of RVH. KCNK3 mRNA level is also reduced in human RV tissues from PAH
      patients compared to non-PAH patients. In line with these findings, chronic
      inhibition of KCNK3 in rats with the specific inhibitor (A293) induces RV
      hypertrophy which is associated with the re-expression of foetal genes, RV
      fibrosis, RV inflammation, and subsequent loss of RV performance as assessed by
      echocardiography. Conclusion: Our data indicate that loss of KCNK3 function and
      expression is a hallmark of the RV hypertrophy/dysfunction associated with PH.

PMID- 29360954
TI  - Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community
      Acquired Pneumonia.

PMID- 29360953
TI  - Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKIIdelta
      expression in the aged atrium.
AB  - Aims: c-jun N-terminal kinase (JNK) is a critical stress response kinase that
      activates in a wide range of physiological and pathological cellular processes.
      We recently discovered a pivotal role of JNK in the development of atrial
      arrhythmias in the aged heart, while cardiac CaMKIIdelta, another pro-arrhythmic
      molecule, was also known to enhance atrial arrhythmogenicity. Here, we aimed to
      reveal a regulatory role of the stress kinase JNK2 isoform on CaMKIIdelta
      expression. Methods and results: Activated JNK2 leads to increased CaMKIIdelta
      protein expression in aged human and mouse atria, evidenced from the reversal of
      CaMKIIdelta up-regulation in JNK2 inhibitor treated wild-type aged mice. This
      JNK2 action in CaMKIIdelta expression was further confirmed in HL-1 myocytes co
      infected with AdMKK7D-JNK2, but not when co-infected with AdMKK7D-JNK1. JNK2
      specific inhibition (either by a JNK2 inhibitor or overexpression of inactivated
      dominant-negative JNK2 (JNK2dn) completely attenuated JNK activator anisomycin
      induced CaMKIIdelta up-regulation in HL-1 myocytes, whereas overexpression of
      JNK1dn did not. Moreover, up-regulated CaMKIIdelta mRNA along with substantially
      increased phosphorylation of JNK downstream transcription factor c-jun [but not
      activating transcription factor2 (ATF2)] were exhibited in both aged atria
      (humans and mice) and transiently JNK activated HL-1 myocytes. Cross-linked
      chromatin-immunoprecipitation assays (XChIP) revealed that both c-jun and ATF2
      were bound to the CaMKIIdelta promoter, but significantly increased binding of c
      jun only occurred in the presence of anisomycin and JNK inhibition alleviated
      this anisomycin-elevated c-jun binding. Mutated CaMKII consensus c-jun binding
      sites impaired its promoter activity. Enhanced transcriptional activity of
      CaMKIIdelta by anisomycin was also completely reversed to the baseline by either
      JNK2 siRNA or c-jun siRNA knockdown. Conclusion: JNK2 activation up-regulates
      CaMKIIdelta expression in the aged atrium. This JNK2 regulation in CaMKIIdelta
      expression occurs at the transcription level through the JNK downstream
      transcription factor c-jun. The discovery of this novel molecular mechanism of
      JNK2-regulated CaMKII expression sheds new light on possible anti-arrhythmia drug
      development.

PMID- 29360955
TI  - Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis.
AB  - In the present review, we describe the causes and consequences of loss of
      vascular smooth muscle cells (VSMCs) or their function in advanced
      atherosclerotic plaques and discuss possible mechanisms such as cell death or
      senescence, and induction of autophagy to promote cell survival. We also
      highlight the potential use of pharmacological modulators of these processes to
      limit plaque progression and/or improve plaque stability. VSMCs play a pivotal
      role in atherogenesis. Loss of VSMCs via initiation of cell death leads to
      fibrous cap thinning and promotes necrotic core formation and calcification. VSMC
      apoptosis is induced by pro-inflammatory cytokines, oxidized low density
      lipoprotein, high levels of nitric oxide and mechanical injury. Apoptotic VSMCs
      are characterized by a thickened basal lamina surrounding the cytoplasmic
      remnants of the VSMC. Inefficient clearance of apoptotic VSMCs results in
      secondary necrosis and subsequent inflammation. A critical determinant in the
      VSMC stress response and phenotypic switching is autophagy, which is activated by
      various stimuli, including reactive oxygen and lipid species, cytokines, growth
      factors and metabolic stress. Successful autophagy stimulates VSMC survival,
      whereas reduced autophagy promotes age-related changes in the vasculature.
      Recently, an interesting link between autophagy and VSMC senescence has been
      uncovered. Defective VSMC autophagy accelerates not only the development of
      stress-induced premature senescence but also atherogenesis, albeit without
      worsening plaque stability. VSMC senescence in atherosclerosis is likely a result
      of replicative senescence and/or stress-induced premature senescence in response
      to DNA damaging and/or oxidative stress-inducing stimuli. The finding that VSMC
      senescence can promote atherosclerosis further illustrates that normal, adequate
      VSMC function is crucial in protecting the vessel wall against atherosclerosis.

PMID- 29360956
TI  - Primer3_masker: integrating masking of template sequence with primer design
      software.
AB  - Summary: Designing PCR primers for amplifying regions of eukaryotic genomes is a
      complicated task because the genomes contain a large number of repeat sequences
      and other regions unsuitable for amplification by PCR. We have developed a novel
      k-mer based masking method that uses a statistical model to detect and mask
      failure-prone regions on the DNA template prior to primer design. We implemented
      the software as a standalone software primer3_masker and integrated it into the
      primer design program Primer3. Availability and implementation: The standalone
      version of primer3_masker is implemented in C. The source code is freely
      available at https://github.com/bioinfo-ut/primer3_masker/ (standalone version
      for Linux and macOS) and at https://github.com/primer3-org/primer3/ (integrated
      version). Primer3 web application that allows masking sequences of 196 animal and
      plant genomes is available at http://primer3.ut.ee/. Contact: maido.remm@ut.ee.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29360957
TI  - Procalcitonin as a Marker of Etiology in Community-Acquired Pneumonia.

PMID- 29360958
TI  - Connections between unemployment insurance, poverty and health: a systematic
      review.
AB  - Background: Since the global economic crisis in 2007, unemployment rates have
      escalated in most European and North American countries. Unemployment protection
      policies, particularly the unemployment insurance (UI) system, have become a
      weighty issue for many modern welfare states. Decades of research have
      established concrete findings on the adverse impacts of unemployment on poverty-
      and health-related outcomes. This provided a foundation for further exploration
      into the potential protective effects of UI in offsetting these adverse outcomes.
      Methods: We developed a systematic review protocol in four stages (literature
      search, study selection, data extraction and quality appraisal) to ensure a
      rigorous data collection and inter-rated reliability. We examined the full body
      of empirical research published between 2000 and 2013 on the pathways by which UI
      impacts poverty and health. Results: Out of 2233 primary studies identified, a
      total of 12 met our inclusion criteria. The selected studies assessed poverty
      related outcomes (absolute/relative poverty and material hardship) or one or more
      health-related outcomes (health behaviors, self-rated health, well-being and
      mental health). Across various UI systems, jurisdictions from high income
      countries, and study designs, we found good support for our conceptual framework,
      by which UI attenuates the effect of unemployment on both poverty and health,
      with a few exceptions. Conclusion: Whether UI impacts differ by age and region
      might be explored further in future research. The complex mediating relationship
      between unemployment, UI, poverty and health should further be assessed in light
      of economic and historical contexts. This could inform decision-making processes
      during future periods of economic recession.

PMID- 29360960
TI  - Community structure of photosynthetic picoeukaryotes differs in lakes with
      different trophic statuses along the middle-lower reaches of the Yangtze River.
AB  - Photosynthetic picoeukaryotes (PPEs) play an important role in aquatic ecosystem
      functioning. There is still a relative lack of information on freshwater PPEs,
      especially in eutrophic lakes. We used a combination of flow cytometric sorting
      and pyrosequencing to investigate the PPEs community structure in more than 20
      mesotrophic and eutrophic lakes along the middle-lower reaches of the Yangtze
      River in China. The abundance of PPEs ranged between 2.04 * 103 and 5.92 * 103
      cells mL-1. The contribution of PPEs to total picophytoplankton abundance was
      generally higher in eutrophic lakes than in mesotrophic lakes. The sequencing
      results indicated that the Shannon diversity of PPEs was significantly higher in
      mesotrophic lakes than in eutrophic lakes. At the class level, PPEs were mainly
      dominated by three taxonomic groups, including Cryptophyceae, Coscinodiscophyceae
      and Chlorophyceae, and 15 additional known phytoplankton classes, including
      Synurophyceae, Dinophyceae, Chrysophyceae, Trebouxiophyceae and Prymnesiophyceae,
      were identified. Coscinodiscophyceae dominated in the most eutrophic lakes, while
      Chrysophyceae, Dinophyceae and other classes of PPEs were more abundant in the
      mesotrophic lakes. We also observed several PPEs operational taxonomic units, and
      those affiliated with Cyclotella atomus, Chlamydomonas sp. and Poterioochromonas
      malhamensis tended to be more prevalent in the eutrophic lakes. The canonical
      correspondence analysis and Mantel analysis highlighted the importance of
      environmental parameters as key drivers of PPEs community composition.

PMID- 29360961
TI  - Occurrence and abundance of antibiotic resistance genes in agricultural soil
      receiving dairy manure.
AB  - Animal manures are commonly used to enhance soil fertility, but there are growing
      concerns over the impact of this practice on the development and dissemination of
      antibiotic resistance. The aim of this field study was to determine the effect of
      annual dairy manure applications on the occurrence and abundance of antibiotic
      resistance genes (ARGs) in an agricultural soil during four years of crop
      production. Treatments included (i) control (no fertilizer or manure), (ii)
      inorganic fertilizer and (iii) dairy manure at three application rates.
      Quantitative PCR was used to determine absolute (per g dry soil) and relative
      (per 16S rRNA gene) abundances of ARGs in DNA extracted from soils. Six ARGs and
      one class 1 integron were targeted. This study found that (i) manure application
      increases ARG abundances above background soil levels; (ii) the higher the manure
      application rate, the higher the ARG abundance in soil; (iii) the amount of
      manure applied is more important than reoccurring annual applications of the same
      amount of manure; (iv) absolute abundance and occurrence of ARGs decreases with
      increasing soil depth, but relative abundances remained constant. This study
      demonstrated that dairy manure applications to soil significantly increase the
      abundance of clinically relevant ARGs when compared to control and inorganic
      fertilized plots.

PMID- 29360959
TI  - Disentangling the Causes for Faster-X Evolution in Aphids.
AB  - The faster evolution of X chromosomes has been documented in several species, and
      results from the increased efficiency of selection on recessive alleles in
      hemizygous males and/or from increased drift due to the smaller effective
      population size of X chromosomes. Aphids are excellent models for evaluating the
      importance of selection in faster-X evolution because their peculiar life cycle
      and unusual inheritance of sex chromosomes should generally lead to equivalent
      effective population sizes for X and autosomes. Because we lack a high-density
      genetic map for the pea aphid, whose complete genome has been sequenced, we first
      assigned its entire genome to the X or autosomes based on ratios of sequencing
      depth in males (X0) to females (XX). Then, we computed nonsynonymous to
      synonymous substitutions ratios (dN/dS) for the pea aphid gene set and found
      faster evolution of X-linked genes. Our analyses of substitution rates, together
      with polymorphism and expression data, showed that relaxed selection is likely to
      be the greatest contributor to faster-X because a large fraction of X-linked
      genes are expressed at low rates and thus escape selection. Yet, a minor role for
      positive selection is also suggested by the difference between substitution rates
      for X and autosomes for male-biased genes (but not for asexual female-biased
      genes) and by lower Tajima's D for X-linked compared with autosomal genes with
      highly male-biased expression patterns. This study highlights the relevance of
      organisms displaying alternative chromosomal inheritance to the understanding of
      forces shaping genome evolution.

PMID- 29360962
TI  - Low Doses of Azathioprine are Effective in Combination With Infliximab in
      Inflammatory Bowel Disease but May not be During Induction Therapy.

PMID- 29360963
TI  - Nitrite-oxidizing activity responds to nitrite accumulation in soil.
AB  - The factors influencing how soil nitrite (NO2-)- and ammonia (NH3)-oxidizing
      activities remain coupled are unknown. A short-term study (<48 h) was conducted
      to examine the dynamics of NO2--oxidizing activity and the accumulation of NO2-
      in three Oregon soils stimulated by the addition of 1 mM NH4+ in soil slurry.
      Nitrite initially accumulated in all three soils; its subsequent decline or
      slowing of the accumulation of the NO2- pool by 24 h was accompanied by an
      increase in the size of the nitrate (NO3-) pool, indicating a change in NO2-
      oxidation kinetics. Bacterial protein synthesis inhibitors prevented the NO2-
      pool decline, resulting in a larger accumulation in all three soils. Although no
      significant increases in NO2--oxidizing bacteria nxrA (Nitrobacter) and nxrB
      (Nitrospira) gene abundances were detected over the time course, maximum NO2-
      consumption rates increased 2-fold in the treatment without antibiotics compared
      to no change with antibiotics. No changes were observed in the apparent half
      saturation constant (Km) values for NO2- consumption. This study demonstrates
      phenotypic flexibility among soil NO2- oxidizers, which can undergo protein
      synthesis-dependent increases in NO2- consumption rates to match NH3 oxidation
      rates and recouple nitrification.

PMID- 29360965
TI  - Reimplantation of the upper lobe bronchus after lower sleeve lobectomy or
      bilobectomy: long-term results.
AB  - OBJECTIVES: The advantages of a bronchial sleeve resection are well established.
      A clear majority of reported cases are of upper lobe sleeve resection.
      Reimplantation of the upper lobe bronchus after a lower sleeve lobectomy or
      bilobectomy (the so-called Y-sleeve resection) is infrequent. Related technical
      peculiarities are the main issues. We present our experience and results in this
      setting. METHODS: Between 1989 and 2015, we performed 28 Y-sleeve resections of
      the left lower lobe (n = 18) or right middle and lower lobes (n = 10). The lung
      sparing reconstructive operation was performed for non-small-cell lung cancer in
      23 cases, for bronchial carcinoid tumour in 4 cases and for a cystic adenoid
      carcinoma in 1 case. Anastomotic reconstruction was performed by interrupted 4-0
      absorbable sutures (monofilament material). RESULTS: All the resections were
      complete (R0). Postoperative mortality was 3.6%. The rate of major complications
      was 10.7% (1 myocardial infarction, 1 anastomotic stenosis requiring dilatation
      and 1 anastomotic fistula). Among the 23 patients with non-small-cell lung cancer
      (18 men and 5 women; mean age 58 +/- 12 years), 8 were Stage I, 9 were Stage II
      and 6 were Stage IIIa. At a mean follow-up of 46 months, the recurrence rate was
      32%. There were 2 loco-regional recurrences. No endobronchial or perianastomotic
      recurrence occurred. The 3- and 5-year overall and disease-free survival rates of
      patients with non-small-cell lung cancer were 76.3% and 55.1% and 68.7% and
      62.9%, respectively. CONCLUSIONS: A Y-sleeve resection with reimplantation of the
      upper load bronchus is a technically feasible and oncologically adequate
      operation.

PMID- 29360966
TI  - Corrigendum to: The EHJ Editorial Board Meeting.

PMID- 29360964
TI  - Deciphering the Link between Doubly Uniparental Inheritance of mtDNA and Sex
      Determination in Bivalves: Clues from Comparative Transcriptomics.
AB  - Bivalves exhibit an astonishing diversity of sexual systems and sex-determining
      mechanisms. They can be gonochoric, hermaphroditic or androgenetic, with both
      genetic and environmental factors known to determine or influence sex. One unique
      sex-determining system involving the mitochondrial genome has also been
      hypothesized to exist in bivalves with doubly uniparental inheritance (DUI) of
      mtDNA. However, the link between DUI and sex determination remains obscure. In
      this study, we performed a comparative gonad transcriptomics analysis for two DUI
      possessing freshwater mussel species to better understand the mechanisms
      underlying sex determination and DUI in these bivalves. We used a BLAST
      reciprocal analysis to identify orthologs between Venustaconcha ellipsiformis and
      Utterbackia peninsularis and compared our results with previously published sex
      specific bivalve transcriptomes to identify conserved sex-determining genes. We
      also compared our data with other DUI species to identify candidate genes
      possibly involved in the regulation of DUI. A total of ~12,000 orthologous
      relationships were found, with 2,583 genes differentially expressed in both
      species. Among these genes, key sex-determining factors previously reported in
      vertebrates and in bivalves (e.g., Sry, Dmrt1, Foxl2) were identified, suggesting
      that some steps of the sex-determination pathway may be deeply conserved in
      metazoans. Our results also support the hypothesis that a modified ubiquitination
      mechanism could be responsible for the retention of the paternal mtDNA in male
      bivalves, and revealed that DNA methylation could also be involved in the
      regulation of DUI. Globally, our results suggest that sets of genes associated
      with sex determination and DUI are similar in distantly-related DUI species.

PMID- 29360968
TI  - Porcine parvovirus infection impairs progesterone production in luteal cells
      through mitogen-activated protein kinases, p53, and mitochondria-mediated
      apoptosis.
AB  - Porcine parvovirus (PPV) is a major virus that leads to fetal death in swine.
      However, the effects of PPV infection on sows are poorly understood. The aim of
      this study was to investigate the effects of PPV on porcine steroidogenic luteal
      cells (SLCs) survival and functions and underlying mechanisms. In vivo experiment
      results showed that artificial infection of PPV significantly reduced the
      concentration of serum progesterone and induced histopathological lesions and
      SLCs apoptosis in porcine corpora luteum. In in vitro cultured primary porcine
      SLCs, PPV could infect and replicate in SLCs and induced SLCs apoptosis through
      mitochondria, but not the death receptor, mediated apoptosis pathway. Meanwhile,
      PPV infection also decreased progesterone production in SLCs. Moreover, PPV
      infection could increase active p53 transcriptional activity and protein
      expression as well as promoting p53 translocation to nucleus. Using the p53
      specific pharmacological inhibitor (pifithrin-alpha) and siRNA could partially
      attenuate PPV-induced Bax upregulation, caspase-3 activation, apoptosis, and the
      reduction of progesterone production in primary porcine SLCs. Furthermore, the
      phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also increased
      in PPV-infected SLCs. Pretreatment with p38 MAPK inhibitor (SB203580) suppressed
      PPV-induced p53 accumulation and translocation, SLCs apoptosis, and progesterone
      production reduction. In summary, these findings indicate that PPV could induce
      SLCs apoptosis and a decrease of progesterone production in vivo and in vitro via
      p38 MAPK signaling and p53-dependent mitochondrial pathway, which provides the
      potential clinical therapy methods for PPV infection.

PMID- 29360967
TI  - Phylogenomics Places Orphan Protistan Lineages in a Novel Eukaryotic Super-Group.
AB  - Recent phylogenetic analyses position certain "orphan" protist lineages deep in
      the tree of eukaryotic life, but their exact placements are poorly resolved. We
      conducted phylogenomic analyses that incorporate deeply sequenced transcriptomes
      from representatives of collodictyonids (diphylleids), rigifilids, Mantamonas,
      and ancyromonads (planomonads). Analyses of 351 genes, using site-heterogeneous
      mixture models, strongly support a novel super-group-level clade that includes
      collodictyonids, rigifilids, and Mantamonas, which we name "CRuMs". Further, they
      robustly place CRuMs as the closest branch to Amorphea (including animals and
      fungi). Ancyromonads are strongly inferred to be more distantly related to
      Amorphea than are CRuMs. They emerge either as sister to malawimonads, or as a
      separate deeper branch. CRuMs and ancyromonads represent two distinct major
      groups that branch deeply on the lineage that includes animals, near the most
      commonly inferred root of the eukaryote tree. This makes both groups crucial in
      examinations of the deepest-level history of extant eukaryotes.

PMID- 29360969
TI  - Feasibility of drugs in Brugada syndrome.

PMID- 29360970
TI  - Successful treatment of a false left ventricular aneurysm after transcatheter
      aortic valve replacement.

PMID- 29360971
TI  - Three-Dimensional Imaging of the Face: A Comparison Between Three Different
      Imaging Modalities.
AB  - Background: Three-dimensional (3D) imaging of the face is being used extensively
      in medicine for clinical decision making, surgical planning, and research.
      Nowadays, several companies are offering a broad range of 3D imaging systems,
      varying in price, method, and mobility. However, most planning and evaluation
      methods are created and validated solely with one imaging system. Therefore, it
      is important to analyze possible differences in the 3D surface reconstruction
      between different systems. Objectives: The objective of this study was to analyze
      differences in the 3D surface reconstruction between three systems: 3dMDface
      system, Vectra XT, and Artec Eva. Methods: Three-dimensional images of the face
      were acquired from 15 healthy patients with each imaging system. Reproducibility
      of each device was calculated and a comparison of the Vectra XT and Artec Eva
      with the 3dMDface was made. Results: All 3D imaging devices showed high
      reproducibility, with a mean difference of 0.18 +/- 0.15 mm (3dMDface system),
      0.15 +/- 0.15 mm (Vectra XT), and 0.26 +/- 0.24 mm (Artec Eva). No significant
      difference in reproducibility was found between the Vectra XT and 3dMDface, while
      a significant difference was found between 3dMDface and Artec Eva, and between
      Vectra XT and Artec Eva. The mean difference between 3dMDface and Vectra XT was
      0.32 +/- 0.26 mm. The mean difference between 3dMDface and Artec Eva was 0.44 +/-
      1.09 mm. Conclusions: All three imaging devices showed high reproducibility and
      accuracy. Although the Artec Eva showed a significant lower reproducibility, the
      difference found was not clinically relevant. Therefore, using these different
      systems alongside each other in clinical and research settings is possible. Level
      of Evidence 3: 

PMID- 29360972
TI  - Stroke after emergent surgery for acute type A aortic dissection: predictors,
      outcome and neurological recovery.
AB  - OBJECTIVES: Despite improvement in operative and cerebral perfusion techniques,
      cerebral malperfusion and neurological injury remain a dreaded complication of
      acute type A aortic dissection. We aimed to identify predictors for postoperative
      stroke and analyse the impact on morbidity, neurological recovery and mid-term
      survival. METHODS: Between 2000 and 2017, 303 (71.9% men, mean age 58.9 +/- 13.6
      years) patients with acute type A aortic dissection underwent surgical repair.
      Clinical and imaging data were retrospectively evaluated. Patients were divided
      into 2 groups depending on the presence of postoperative stroke. RESULTS:
      Postoperative stroke was detected in 15.8% (n = 48) of the patients. Patients
      with postoperative stroke showed higher rates of preoperative cardiopulmonary
      resuscitation (stroke: 18.8% vs no stroke: 3.5%, P < 0.001) and malperfusion
      syndrome (stroke: 47.9% vs no stroke: 22.4%, P < 0.001). Multivariable analysis
      identified the presence of bovine aortic arch [odds ratio (OR) 2.33, 95%
      confidence interval (CI) 1.086-4.998; P = 0.030], preoperative cardiopulmonary
      resuscitation (OR 6.483, 95% CI 1.522-27.616; P = 0.011) and preoperative
      malperfusion (OR 2.536, 95% CI 1.238-5.194; P = 0.011) as independent predictors
      for postoperative stroke. Postoperative stroke had a strong impact on morbidity
      and was associated with higher rates of postoperative complications and a
      significantly longer hospital stay (stroke: 23 +/- 16 days vs no stroke: 17 +/-
      18 days, P = 0.021). Postoperative stroke was not independently associated with
      in-hospital mortality (adjusted OR 1.382, 95% CI 0.518-3.687; P = 0.518). There
      was no difference in mid-term survival between patients with stroke and patients
      without stroke. CONCLUSIONS: This study identified independent preoperative
      predictors for postoperative stroke. Although postoperative stroke was associated
      with significant morbidity and postoperative complications, significant
      impairment in mid-term survival could not be confirmed by the data.

PMID- 29360973
TI  - Transcriptome profiling reveals infection strategy of an insect maculavirus.
AB  - Bombyx mori macula-like virus (BmMLV) is a positive, single-stranded insect RNA
      virus that is closely related to plant maculaviruses. BmMLV is currently
      characterized as an unclassified maculavirus. BmMLV accumulates at extremely high
      levels in cell lines derived from the silkworm, Bombyx mori, but it does not lead
      to lethality and establishes persistent infections. It is unknown how this insect
      maculavirus replicates and establishes persistent infections in insect cells.
      Here, we showed that BmMLV p15, which is located on a subgenomic fragment and is
      not found in plant maculaviruses, is highly expressed in BmMLV-infected silkworm
      cells and that p15 protein is required to establish BmMLV infections in silkworm
      cells. We also showed that two distinct small RNA-mediated pathways maintain
      BmMLV levels in BmMLV-infected silkworm cells, thereby allowing the virus to
      establish persistent infection. Virus-derived siRNAs and piRNAs were both
      produced as the infection progressed. Knockdown experiments demonstrated that the
      exogenous RNAi pathway alone or RNAi and piRNA pathways function cooperatively to
      silence BmMLV RNA and that both pathways are important for normal growth of BmMLV
      infected silkworm cells. On the basis of our study, we propose a mechanism of how
      a plant virus-like insect virus can establish persistent infections in insect
      cells.

PMID- 29360974
TI  - Use of leadless pacemakers in Europe: results of the European Heart Rhythm
      Association survey.
AB  - The purpose of this European Heart Rhythm Association (EHRA) survey is to provide
      an overview of the current use of leadless pacemakers (LLPM) across a broad range
      of European centres. An online questionnaire was sent to centres participating in
      the EHRA Electrophysiology Research Network. Questions dealt with standards of
      care and policies used for patient management, indications, and techniques of
      implantation of LLPM. In total, 52 centres participated in the survey. Most (86%)
      reported using LLPM, although 82% of these centres implanted <30 LLPM devices
      during the last 12 months. Non-availability (36%), lack of reimbursement (55%),
      and cost of the device (91%) were factors limiting the use of LLPM. The most
      commonly reported indications for LLPM were permanent atrial fibrillation (83%),
      a history of complicated conventional pacemaker (87%), or an anticipated
      difficult vascular access (91%). Implantation of LLPM is perceived as an easy-to
      do and safe procedure by most implanters (64%), while difficult or risky in 28%,
      and comparable to conventional pacemakers by only a few (8%). Local vascular
      complications were the most frequently reported major problems (28%), but a
      significant number of respondents (36%) have never encountered any issue after
      LLPM implantation. Although cost and reimbursement issues strongly influence the
      use of LLPM, most respondents (72%) anticipate a significant increase in device
      utilization within next 2 years.

PMID- 29360975
TI  - Comparative Genomics of Tenacibaculum dicentrarchi and "Tenacibaculum
      finnmarkense" Highlights Intricate Evolution of Fish-Pathogenic Species.
AB  - The genus Tenacibaculum encompasses several species pathogenic for marine fish.
      Tenacibaculum dicentrarchi and "Tenacibaculum finnmarkense" (Quotation marks
      denote species that have not been validly named.) were retrieved from skin
      lesions of farmed fish such as European sea bass or Atlantic salmon. They cause a
      condition referred to as tenacibaculosis and severe outbreaks and important fish
      losses have been reported in Spanish, Norwegian, and Chilean marine farms. We
      report here the draft genomes of the T. dicentrarchi and "T. finnmarkense" type
      strains. These genomes were compared with draft genomes from field isolates
      retrieved from Chile and Norway and with previously published Tenacibaculum
      genomes. We used Average Nucleotide Identity and core genome-based phylogeny as a
      proxy index for species boundary delineation. This work highlights evolution of
      closely related fish-pathogenic species and suggests that homologous
      recombination likely contributes to genome evolution. It also corrects the
      species affiliation of strain AYD7486TD claimed by Grothusen et al. (2016).

PMID- 29360976
TI  - Transcriptional regulation of the mannan utilization genes in the alkaliphilic
      Bacillus sp. N16-5.
AB  - Bacillus sp. N16-5 is an alkaliphile with a great ability to utilize mannan. Its
      mannan utilization gene cluster has been identified in a previous study. The ManR
      protein encoded by the cluster was predicted to be a LacI family regulator, and
      the transcription level of the mannan utilization gene cluster was upregulated
      after the manR gene was deleted, indicating that ManR is the repressor of this
      cluster. The transcription of the related genes was downregulated when manH,
      encoding the extracellular substrate-binding domain of the manno-oligosaccharide
      transporter, was deleted. Furthermore, isothermal titration calorimetry revealed
      that mannotetraose and mannopentose are ligands of ManR. These results all
      corroborate the hypothesis that the mannan utilization gene cluster is repressed
      by the transcription regulator ManR, and that the repression is removed when it
      binds to manno-oligosaccharides, which are generated by mannan degradation and
      transported into the cell by a specific transporter.

PMID- 29360977
TI  - ATP-binding cassette transporters of the multicellular cyanobacterium Anabaena
      sp. PCC 7120: a wide variety for a complex lifestyle.
AB  - Two hundred genes or 3% of the known or putative protein-coding genes of the
      filamentous freshwater cyanobacterium Anabaena sp. PCC 7120 encode domains of ATP
      binding cassette (ABC) transporters. Detailed characterization of some of these
      transporters (14-15 importers and 5 exporters) has revealed their crucial roles
      in the complex lifestyle of this multicellular photoautotroph, which is able to
      differentiate specialized cells for nitrogen fixation. This review summarizes the
      characteristics of the ABC transporters of Anabaena sp. PCC 7120 known to date.

PMID- 29360979
TI  - Dissemination of linezolid-dependent, linezolid-resistant Staphylococcus
      epidermidis clinical isolates belonging to CC5 in German hospitals.
AB  - Objectives: Linezolid-resistant Staphylococcus epidermidis (LRSE) and linezolid
      dependent ST22 strains have been shown to predominate in tertiary care facilities
      all over Greece. We report herein the dissemination of ST22 but also ST2, ST5 and
      ST168 linezolid-dependent LRSE clones in four unrelated German hospitals.
      Methods: Fourteen LRSE clinical isolates recovered during 2012-14 from five
      distantly located German hospitals were tested by for MIC determination broth
      microdilution and Etest, PCR/sequencing for cfr and for mutations in 23S rRNA,
      rplC, rplD and rplV genes, MLST, PFGE and growth curves without and with
      linezolid at 16 and 32 mg/L. Results: Most (11, 78.6%) isolates had linezolid
      MICs >256 mg/L. Five isolates carried the cfr gene. Eight isolates belonged to
      ST22, two isolates each to ST168 and ST2 and one isolate each to ST5 and ST23.
      Ten isolates [seven belonging to ST22 and one to each of ST2, ST5 and ST168; all
      these STs belong to clonal complex (CC) 5] exhibited linezolid-dependent growth,
      growing significantly faster in linezolid-containing broth. Four isolates were
      non-dependent (one belonging to each of ST22, ST2, ST23 and ST168). Four isolates
      came from three different hospitals, whereas four and six isolates were recovered
      during outbreaks of LRSE in two distinct hospitals. Conclusions: The multi-clonal
      dissemination of CC5 linezolid-dependent LRSE throughout German hospitals along
      with the clonal expansion of ST22 linezolid-dependent LRSE in Greek hospitals is
      of particular concern. It is plausible that this characteristic is inherent and
      provides a selective advantage to CC5 LRSE under linezolid pressure, contributing
      to their dissemination throughout hospitals in these countries.

PMID- 29360978
TI  - Comparative Genomics Reveals Accelerated Evolution in Conserved Pathways during
      the Diversification of Anole Lizards.
AB  - Squamates include all lizards and snakes, and display some of the most diverse
      and extreme morphological adaptations among vertebrates. However, compared with
      birds and mammals, relatively few resources exist for comparative genomic
      analyses of squamates, hampering efforts to understand the molecular bases of
      phenotypic diversification in such a speciose clade. In particular, the ~400
      species of anole lizard represent an extensive squamate radiation. Here, we
      sequence and assemble the draft genomes of three anole species-Anolis frenatus,
      Anolis auratus, and Anolis apletophallus-for comparison with the available
      reference genome of Anolis carolinensis. Comparative analyses reveal a rapid
      background rate of molecular evolution consistent with a model of punctuated
      equilibrium, and strong purifying selection on functional genomic elements in
      anoles. We find evidence for accelerated evolution in genes involved in behavior,
      sensory perception, and reproduction, as well as in genes regulating limb bud
      development and hindlimb specification. Morphometric analyses of anole fore and
      hindlimbs corroborated these findings. We detect signatures of positive selection
      across several genes related to the development and regulation of the forebrain,
      hormones, and the iguanian lizard dewlap, suggesting molecular changes underlying
      behavioral adaptations known to reinforce species boundaries were a key component
      in the diversification of anole lizards.

PMID- 29360980
TI  - Testicular MTHFR deficiency may explain sperm DNA hypomethylation associated with
      high dose folic acid supplementation.
AB  - Supplementation with high doses of folic acid, an important mediator of one
      carbon transfers for DNA methylation, is used clinically to improve sperm
      parameters in infertile men. We recently detected an unexpected loss of DNA
      methylation in the sperm of idiopathic infertile men after 6 months of daily
      supplementation with 5 mg folic acid (>10* the daily recommended intake-DRI),
      exacerbated in men homozygous for a common variant in the gene encoding an
      important enzyme in folate metabolism, methylenetetrahydrofolate reductase (MTHFR
      677C>T). To investigate the epigenomic impact and mechanism underlying effects of
      folic acid on male germ cells, wild-type and heterozygote mice for a targeted
      inactivation of the Mthfr gene were fed high-dose folic acid (10* the DRI) or
      control diets (CDs) for 6 months. No changes were detected in general health,
      sperm counts or methylation of imprinted genes. Reduced representation bisulfite
      sequencing revealed sperm DNA hypomethylation in Mthfr+/- mice on the 10* diets.
      Wild-type mice demonstrated sperm hypomethylation only with a very high dose
      (20*) of folic acid for 12 months. Testicular MTHFR protein levels decreased
      significantly in wild-type mice on the 20* diet but not in those on the 10* diet,
      suggesting a possible role for MTHFR deficiency in sperm DNA hypomethylation. In
      depth analysis of the folic acid-exposed sperm DNA methylome suggested
      mouse/human susceptibility of sequences with potential importance to germ cell
      and embryo development. Our data provide evidence for a similar cross-species
      response to high dose folic acid supplementation, of sperm DNA hypomethylation,
      and implicate MTHFR downregulation as a possible mechanism.

PMID- 29360982
TI  - Paravalvular mitral leak closure under Eco-X-ray fusion guidance.

PMID- 29360981
TI  - From a dominant to an oligogenic model of inheritance with environmental
      modifiers in acute intermittent porphyria.
AB  - Acute intermittent porphyria (AIP) is a disease affecting the heme biosynthesis
      pathway caused by mutations of the hydroxymethylbilane synthase (HMBS) gene. AIP
      is thought to display autosomal dominant inheritance with incomplete penetrance.
      We evaluated the prevalence, penetrance and heritability of AIP, in families with
      the disease from the French reference center for porphyria (CFP) (602 overt
      patients; 1968 relatives) and the general population, using Exome Variant Server
      (EVS; 12 990 alleles) data. The pathogenicity of the 42 missense variants
      identified was assessed in silico, and in vitro, by measuring residual HMBS
      activity of the recombinant protein. The minimal estimated prevalence of AIP in
      the general population was 1/1299. Thus, 50 000 subjects would be expected to
      carry the AIP genetic trait in France. Penetrance was estimated at 22.9% in
      families with AIP, but at only 0.5-1% in the general population. Intrafamily
      correlation studies showed correlations to be strong overall and modulated by
      kinship and the area in which the person was living, demonstrating strong
      influences of genetic and environmental modifiers on inheritance. Null alleles
      were associated with a more severe phenotype and a higher penetrance than for
      other mutant alleles. In conclusion, the striking difference in the penetrance of
      HMBS mutations between the general population and the French AIP families
      suggests that AIP inheritance does not follow the classical autosomal dominant
      model, instead of being modulated by strong environmental and genetic factors
      independent from HMBS. An oligogenic inheritance model with environmental
      modifiers might better explain AIP penetrance and heritability.

PMID- 29360983
TI  - Modification of histone by glyoxal: recognition of glycated histone containing
      advanced glycation adducts by serum antibodies of type 1 diabetes patients.
AB  - Dicarbonyl compounds react more rapidly, than glucose, with arginine and lysine
      in proteins to form advanced glycation end products (AGEs) and further produce
      free radicals which cause DNA damage. AGEs are reliable diagnostic biomarkers for
      most of the age-related diseases. In the present study histone was modified with
      glyoxal and it was characterized by various spectral techniques. Binding
      characteristics of the modified histone towards serum antibodies from type 1
      diabetes patients was evaluated by solid phase enzyme immunoassay and the results
      were compared with normal human subjects. Fluorescence and Fourier transformed
      infrared analysis of the nuclear protein clearly indicated changes in their
      respective intensities upon modification with glyoxal. Liquid chromatography
      together with mass spectrometry showed new peaks and m/z values related to AGE
      adducts of dihydroimidazolidines/hydroimidazolones. This glyoxal modified protein
      was recognized by serum antibodies of the diabetes patients while it showed
      negligible binding with that of normal human subjects. Glyoxal modification of
      histone causes structural turbulence and formation of advanced glycation adducts
      in histone. These adducts might be the main antigenic epitope of the modified
      histone, leading to its recognition by circulating type 1 diabetes antibodies.

PMID- 29360984
TI  - Regulation of ciliary function by fibroblast growth factor signaling identifies
      FGFR3-related disorders achondroplasia and thanatophoric dysplasia as
      ciliopathies.
AB  - Cilia project from almost every cell integrating extracellular cues with
      signaling pathways. Constitutive activation of FGFR3 signaling produces the
      skeletal disorders achondroplasia (ACH) and thanatophoric dysplasia (TD), but
      many of the molecular mechanisms underlying these phenotypes remain unresolved.
      Here, we report in vivo evidence for significantly shortened primary cilia in ACH
      and TD cartilage growth plates. Using in vivo and in vitro methodologies, our
      data demonstrate that transient versus sustained activation of FGF signaling
      correlated with different cilia consequences. Transient FGF pathway activation
      elongated cilia, while sustained activity shortened cilia. FGF signaling extended
      primary cilia via ERK MAP kinase and mTORC2 signaling, but not through mTORC1.
      Employing a GFP-tagged IFT20 construct to measure intraflagellar (IFT) speed in
      cilia, we showed that FGF signaling affected IFT velocities, as well as
      modulating cilia-based Hedgehog signaling. Our data integrate primary cilia into
      canonical FGF signal transduction and uncover a FGF-cilia pathway that needs
      consideration when elucidating the mechanisms of physiological and pathological
      FGFR function, or in the development of FGFR therapeutics.

PMID- 29360986
TI  - High levels of susceptibility to new and older antibiotics in Neisseria
      gonorrhoeae isolates from Saskatchewan (2003-15): time to consider point-of-care
      or molecular testing for precision treatment?-authors' response.

PMID- 29360987
TI  - Residual echocardiographic and computed tomography findings after thoracoscopic
      occlusion of the left atrial appendage using the AtriClip PRO device.
AB  - OBJECTIVES: Thoracoscopic occlusion of the left atrial appendage (LAA) has become
      a routine part of thoracoscopic ablation for the treatment of atrial fibrillation
      (AF). Evaluation of residual findings of the occluded LAA by echocardiography has
      yet to be described. METHODS: Patients with AF indicated for hybrid ablation
      (thoracoscopic procedure followed by catheter ablation) were enrolled in this
      study. LAA was occluded as a routine part of the thoracoscopic procedure. Follow
      up transoesophageal echocardiography was performed at the end of the procedure, 2
      5 days and 2-3 months after the procedure (before the endocardial stage). The
      residual pouches of the LAA were measured in the mitral valve view (30-110
      degrees ) and in the perpendicular view. The depth of the residual pouch was
      measured from the ostial plane (connecting the Coumadin ridge and the circumflex
      artery) to the deepest part of the residuum. The volume of the residual pouch and
      the distance from the circumflex artery to the proximal and the distal ends of
      the AtriClip were measured using computed tomography. RESULTS: Forty patients
      were enrolled in this study. The success rate for the occlusion of the LAA,
      assessed on transoesophageal echocardiography 2-5 days after surgery, was 97.5%.
      Regarding the residual findings, no reperfused LAAs were found, and only residual
      stumps remained. The depth of the stump was 12.9 +/- 5.9 mm, the area was 2.2 +/-
      1.1 cm2, and the volume was 3.6 +/- 1.9 ml (all data are shown as mean +/-
      standard deviation). CONCLUSIONS: The occlusion of the LAA using an AtriClip PRO
      device was a clinically safe procedure with high efficacy and was associated with
      the presence of a small residual pouch after occlusion. Clinical trial
      registration: NCT02832206.

PMID- 29360985
TI  - Temporal requirement of dystroglycan glycosylation during brain development and
      rescue of severe cortical dysplasia via gene delivery in the fetal stage.
AB  - Congenital muscular dystrophies (CMDs) are characterized by progressive weakness
      and degeneration of skeletal muscle. In several forms of CMD, abnormal
      glycosylation of alpha-dystroglycan (alpha-DG) results in conditions collectively
      known as dystroglycanopathies, which are associated with central nervous system
      involvement. We recently demonstrated that fukutin, the gene responsible for
      Fukuyama congenital muscular dystrophy, encodes the ribitol-phosphate transferase
      essential for dystroglycan function. Brain pathology in patients with
      dystroglycanopathy typically includes cobblestone lissencephaly, mental
      retardation, and refractory epilepsy; however, some patients exhibit average
      intelligence, with few or almost no structural defects. Currently, there is no
      effective treatment for dystroglycanopathy, and the mechanisms underlying the
      generation of this broad clinical spectrum remain unknown. Here, we analysed four
      distinct mouse models of dystroglycanopathy: two brain-selective fukutin
      conditional knockout strains (neuronal stem cell-selective Nestin-fukutin-cKO and
      forebrain-selective Emx1-fukutin-cKO), a FukutinHp strain with the founder
      retrotransposal insertion in the fukutin gene, and a spontaneous Large-mutant
      Largemyd strain. These models exhibit variations in the severity of brain
      pathology, replicating the clinical heterogeneity of dystroglycanopathy.
      Immunofluorescence analysis of the developing cortex suggested that residual
      glycosylation of alpha-DG at embryonic day 13.5 (E13.5), when cortical dysplasia
      is not yet apparent, may contribute to subsequent phenotypic heterogeneity.
      Surprisingly, delivery of fukutin or Large into the brains of mice at E12.5
      prevented severe brain malformation in Emx1-fukutin-cKO and Largemyd/myd mice,
      respectively. These findings indicate that spatiotemporal persistence of
      functionally glycosylated alpha-DG may be crucial for brain development and
      modulation of glycosylation during the fetal stage could be a potential
      therapeutic strategy for dystroglycanopathy.

PMID- 29360988
TI  - CHEK1 coordinates DNA damage signaling and meiotic progression in the male
      germline of mice.
AB  - The continuity of life depends on mechanisms in the germline that ensure the
      integrity of the genome. The DNA damage response/checkpoint kinases ATM and ATR
      are essential signaling factors in the germline. However, it remains unknown how
      a downstream transducer, Checkpoint Kinase 1 (CHEK1 or CHK1), mediates signaling
      in the male germline. Here, we show that CHEK1 has distinct functions in both the
      mitotic and meiotic phases of the male germline in mice. In the mitotic phase,
      CHEK1 is required for the resumption of prospermatogonia proliferation after
      birth and the maintenance of spermatogonia. In the meiotic phase, we uncovered
      two functions for CHEK1: one is the stage-specific attenuation of DNA damage
      signaling on autosomes, and the other is coordination of meiotic stage
      progression. On autosomes, the loss of CHEK1 delays the removal of DNA damage
      signaling that manifests as phosphorylation of histone variant H2AX at serine 139
      (gammaH2AX). Importantly, CHEK1 does not have a direct function in meiotic sex
      chromosome inactivation (MSCI), an essential event in male meiosis, in which ATR
      is a key regulator. Thus, the functions of ATR and CHEK1 are uncoupled in MSCI,
      in contrast to their roles in DNA damage signaling in somatic cells. Our study
      reveals stage-specific functions for CHEK1 that ensure the integrity of the male
      germline.

PMID- 29360990
TI  - PBP4 activity and its overexpression are necessary for PBP4-mediated high-level
      beta-lactam resistance.
AB  - Background: PBP4 is typically considered unimportant for conferring high-level
      beta-lactam resistance in Staphylococcus aureus. Mutations in PBP4 have been
      associated with beta-lactam non-susceptibility among natural strains of S.
      aureus. We have previously shown that PBP4 can mediate high-level beta-lactam
      resistance in laboratory-generated strains passaged in beta-lactam antibiotics.
      Mutations in the pbp4 promoter that up-regulate its expression and missense
      mutations that surround PBP4's active site were detected in high frequencies
      among passaged strains, suggesting PBP4 plays a key role in resistance. How these
      mutations participate in PBP4's ability to provide high-level beta-lactam
      resistance is unknown. Objectives: To determine whether enzymatic activity of
      PBP4 is required for high-level beta-lactam resistance and to investigate how the
      pbp4-associated mutations provide beta-lactam resistance. Methods: The catalytic
      activity of PBP4 was disabled through introduction of a serine to alanine point
      mutation in its active site (Ser-75->Ala) in a representative and well-studied
      passaged strain, CRB. pbp4 promoter and missense mutations detected in CRB were
      reconstituted in a WT strain individually and in combination. beta-Lactam
      resistance of the resultant strains was evaluated by population analysis.
      Bacterial peptidoglycan composition of the pbp4 mutants was evaluated with and
      without antibiotic treatment using LC. Results: PBP4 inactivation imparted
      complete beta-lactam susceptibility of CRB. Reconstitution of PBP4 missense
      mutations alone did not impart beta-lactam resistance, but did so in synergism
      with pbp4 promoter mutation. A similar synergistic interaction of pbp4 mutations
      was observed in enhanced peptidoglycan cross-linking upon antibiotic treatment.
      Conclusions: PBP4's activity and overexpression both contribute to high-level
      beta-lactam resistance.

PMID- 29360991
TI  - Elevated plasma catecholamines functionally compensate for the reduced myogenic
      tone in smooth muscle STIM1 knockout mice but with deleterious cardiac effects.
AB  - Aims: Stromal interaction molecule 1 (STIM1) has emerged as an important player
      in the regulation of growth and proliferation of smooth muscle cells. Therefore,
      we hypothesized that STIM1 plays a crucial role in the maintenance of vascular
      integrity. The objective of this study was to evaluate whether reduced expression
      of STIM1 could modify the structure and function of the vasculature, leading to
      changes in blood pressure (BP). Methods and results: Smooth muscle-specific STIM1
      knockout (sm-STIM1 KO) in mice resulted in arteries with ~80% reduced STIM1
      protein expression as compared with control mice. Mesenteric vessels exposed to
      increasing transmural pressure revealed attenuated myogenic reactivity and
      reduced vasoconstrictor response to phenylephrine in sm-STIM1 KO arteries. BP
      monitored via telemetry in sm-STIM1 KO and matched controls did not reveal
      differences. However, heart rate was significantly increased in sm-STIM1 KO mice.
      Consistent with these findings, plasma catecholamine levels were higher in sm
      STIM1 KO than in control mice. Increased sympathetic activity in sm-STIM1 KO mice
      was unmasked by apha1-adrenergic receptor inhibitor (prazosin) and by treatment
      with the ganglion-blocking agent, hexamethonium. Both treatments resulted in a
      greater reduction of BP in sm-STIM1 KO mice. Cytoskeleton of cultured smooth
      muscle cells was studied by immunocytochemistry using specific antibodies.
      Staining for actin and vinculin revealed significant alterations in the
      cytoskeletal architecture of cells isolated from sm-STIM1 KO arteries. Finally,
      although sm-STIM1 KO mice were protected from Ang II-induced hypertension, such
      treatment resulted in significant fibrosis and a rapid deterioration of cardiac
      function. Conclusions: STIM1 deletion in smooth muscle results in attenuated
      myogenic tone and cytoskeletal defects with detrimental effects on the mechanical
      properties of arterial tissue. Although BP is maintained by elevated circulating
      catecholamine, this compensatory stimulation has a deleterious long-term effect
      on the myocardium.

PMID- 29360992
TI  - The female epilepsy protein PCDH19 is a new GABAAR-binding partner that regulates
      GABAergic transmission as well as migration and morphological maturation of
      hippocampal neurons.
AB  - The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19
      (PCDH19) and is responsible for a neurodevelopmental pathology characterized by
      female-limited epilepsy, cognitive impairment and autistic features, the
      pathogenic mechanisms of which remain to be elucidated. Here, we identified a new
      interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat
      brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and
      affects the frequency and kinetics of miniature inhibitory postsynaptic currents
      (mIPSCs) in cultured hippocampal neurons. In vivo, PCDH19 downregulation impairs
      migration, orientation and dendritic arborization of CA1 hippocampal neurons and
      increases rat seizure susceptibility. In sum, these data indicate a role for
      PCDH19 in GABAergic transmission as well as migration and morphological
      maturation of neurons.

PMID- 29360993
TI  - Unpaid Caregiving Roles and Sleep Among Women Working in Nursing Homes: A
      Longitudinal Study.
AB  - Background and Objectives: Although sleep is a critical health outcome providing
      insight into overall health, well-being, and role functioning, little is known
      about the sleep consequences of simultaneously occupying paid and unpaid
      caregiving roles. This study investigated the frequency with which women employed
      in U.S.-based nursing homes entered and exited unpaid caregiving roles for
      children (double-duty-child caregivers), adults (double-duty-elder caregivers),
      or both (triple-duty caregivers), as well as examined how combinations of and
      changes in these caregiving roles related to cross-sectional and longitudinal
      sleep patterns. Research Design and Methods: The sample comprised 1,135 women
      long-term care employees who participated in the baseline wave of the Work,
      Family, and Health Study and were assessed at three follow-up time points (6-, 12
      , and 18-months). Sleep was assessed with items primarily adapted from the
      Pittsburgh Sleep Quality Index and wrist actigraphic recordings. Multilevel
      models with data nested within persons were applied. Results: Women long-term
      care employees entered and exited the unpaid elder caregiving role most
      frequently. At baseline, double-duty-child and triple-duty caregivers reported
      shorter sleep quantity and poorer sleep quality than their counterparts without
      unpaid caregiving roles, or workplace-only caregivers. Double-duty-elder
      caregivers also reported shorter sleep duration compared to workplace-only
      caregivers. Over time, double-duty-elder caregiving role entry was associated
      with negative changes in subjective sleep quantity and quality. Discussion and
      Implications: Simultaneously occupying paid and unpaid caregiving roles has
      negative implications for subjective sleep characteristics. These results call
      for further research to advance understanding of double-and-triple-duty
      caregivers' sleep health and facilitate targeted intervention development.

PMID- 29360989
TI  - Evolution of drug resistance in Mycobacterium tuberculosis: a review on the
      molecular determinants of resistance and implications for personalized care.
AB  - Drug-resistant TB (DR-TB) remains a significant challenge in TB treatment and
      control programmes worldwide. Advances in sequencing technology have
      significantly increased our understanding of the mechanisms of resistance to anti
      TB drugs. This review provides an update on advances in our understanding of drug
      resistance mechanisms to new, existing drugs and repurposed agents. Recent
      advances in WGS technology hold promise as a tool for rapid diagnosis and
      clinical management of TB. Although the standard approach to WGS of Mycobacterium
      tuberculosis is slow due to the requirement for organism culture, recent attempts
      to sequence directly from clinical specimens have improved the potential to
      diagnose and detect resistance within days. The introduction of new databases may
      be helpful, such as the Relational Sequencing TB Data Platform, which contains a
      collection of whole-genome sequences highlighting key drug resistance mutations
      and clinical outcomes. Taken together, these advances will help devise better
      molecular diagnostics for more effective DR-TB management enabling personalized
      treatment, and will facilitate the development of new drugs aimed at improving
      outcomes of patients with this disease.

PMID- 29360994
TI  - The risk of spinal cord injury during the frozen elephant trunk procedure in
      acute aortic dissection.
AB  - OBJECTIVES: The aim of the study was to access the extended occlusion of the
      intercostal arteries by a stent graft in the development of postoperative spinal
      cord injury during aortic arch surgery using the frozen elephant trunk technique.
      METHODS: A total of 37 consecutive patients underwent total aortic arch surgery
      using the frozen elephant trunk technique between March 2012 and July 2017. The
      mean age of the patients was 54.7 +/- 10.5 years. Type A and Type B aortic
      dissections were the indications for surgery. Moderate hypothermia and antegrade
      cerebral perfusion via the innominate artery were utilized. The mean diameter of
      the implanted stent graft was 27.7 +/- 2 mm (range 24-30 mm). RESULTS: No
      permanent spinal cord injuries occurred. The distal edge of the stent graft was
      in the T7-T12 range. Its lower edge was implanted at the T9-T12 level in 25
      (67.6%) cases. Preoperatively, the mean number of intercostal arteries was 10 +/-
      1 on the left side and 10 +/- 2 on the right side (P = 0.59). Postoperatively,
      the mean number of open segmental arteries was 3 +/- 2 on the left and 4 +/- 1 on
      the right (P = 0.003). CONCLUSIONS: The frozen elephant trunk procedure is
      associated with the occlusion of most (two-thirds) of the intercostal arteries.
      Maintenance of adequate blood flow in the subclavian and iliac arteries is an
      integral prerequisite for a favourable outcome. The level of the deployment of
      the distal edge of the stent graft does not play a defining role.

PMID- 29360995
TI  - Impact of problem-based charting on the utilization and accuracy of the
      electronic problem list.
AB  - Objective: Problem-based charting (PBC) is a method for clinician documentation
      in commercially available electronic medical record systems that integrates note
      writing and problem list management. We report the effect of PBC on problem list
      utilization and accuracy at an academic intensive care unit (ICU). Materials and
      Methods: An interrupted time series design was used to assess the effect of PBC
      on problem list utilization, which is defined as the number of new problems added
      to the problem list by clinicians per patient encounter, and of problem list
      accuracy, which was determined by calculating the recall and precision of the
      problem list in capturing 5 common ICU diagnoses. Results: In total, 3650 and
      4344 patient records were identified before and after PBC implementation at
      Stanford Hospital. An increase of 2.18 problems (>50% increase) in the mean
      number of new problems added to the problem list per patient encounter can be
      attributed to the initiation of PBC. There was a significant increase in recall
      attributed to the initiation of PBC for sepsis (beta = 0.45, P < .001) and acute
      renal failure (beta = 0.2, P = .007), but not for acute respiratory failure,
      pneumonia, or venous thromboembolism. Discussion: The problem list is an
      underutilized component of the electronic medical record that can be a source of
      clinician-structured data representing the patient's clinical condition in real
      time. PBC is a readily available tool that can integrate problem list management
      into physician workflow. Conclusion: PBC improved problem list utilization and
      accuracy at an academic ICU.

PMID- 29360996
TI  - Feature specific quantile normalization enables cross-platform classification of
      molecular subtypes using gene expression data.
AB  - Motivation: Molecular subtypes of cancers and autoimmune disease, defined by
      transcriptomic profiling, have provided insight into disease pathogenesis,
      molecular heterogeneity and therapeutic responses. However, technical biases
      inherent to different gene expression profiling platforms present a unique
      problem when analyzing data generated from different studies. Currently, there is
      a lack of effective methods designed to eliminate platform-based bias. We present
      a method to normalize and classify RNA-seq data using machine learning
      classifiers trained on DNA microarray data and molecular subtypes in two
      datasets: breast invasive carcinoma (BRCA) and colorectal cancer (CRC). Results:
      Multiple analyses show that feature specific quantile normalization (FSQN)
      successfully removes platform-based bias from RNA-seq data, regardless of feature
      scaling or machine learning algorithm. We achieve up to 98% accuracy for BRCA
      data and 97% accuracy for CRC data in assigning molecular subtypes to RNA-seq
      data normalized using FSQN and a support vector machine trained exclusively on
      DNA microarray data. We find that maximum accuracy was achieved when normalizing
      RNA-seq datasets that contain at least 25 samples. FSQN allows comparison of RNA
      seq data to existing DNA microarray datasets. Using these techniques, we can
      successfully leverage information from existing gene expression data in new
      analyses despite different platforms used for gene expression profiling.
      Availability and implementation: FSQN has been submitted as an R package to CRAN.
      All code used for this study is available on Github
      (https://github.com/jenniferfranks/FSQN). Contact:
      michael.l.whitfield@dartmouth.edu. Supplementary information: Supplementary data
      are available at Bioinformatics online.

PMID- 29360997
TI  - Novel regenerative therapy combined with transphrenic peritoneoscopy-assisted
      omentopexy.
AB  - OBJECTIVES: We previously reported that cell sheet transplantation combined with
      an omentopexy (OP) procedure is more effective for repairing heart damage when
      compared with cell sheet transplantation alone. However, a simultaneous
      (conventional) laparotomy as part of the OP may adversely affect the general
      condition of critically ill heart failure patients who would otherwise benefit
      from cell sheet transplantation, which is a paradox to be reconciled before this
      treatment can be applied in a clinical setting. We devised a novel endoscopic
      approach termed 'transphrenic peritoneoscopy' (TPP) for minimal access to
      abdominal organs from the thoracic cavity. Herein, we evaluated the feasibility
      and safety of TPP with an OP in a porcine myocardial infarction model. METHODS:
      Myocardial infarction was induced in 4 mini pigs by placing an ameroid
      constrictor around the left anterior descending artery. One month later, a left
      thoracotomy was performed in 2 randomly selected mini pigs, and a laparoscopic
      port was placed on the left diaphragm to gain access into the abdominal cavity.
      Using a low-pressure pneumoperitoneum, a flexible gastrointestinal endoscope was
      advanced, then the omentum was partially grasped with endoscopic forceps and
      brought back into the thoracic cavity via the diaphragm. Skeletal myoblast cell
      sheets were then implanted over the impaired myocardium, followed by placing the
      omentum over the sheets. RESULTS: TPP-assisted OP was accomplished in 2 post
      myocardial infarction mini pigs with severe heart failure with an intra-abdominal
      pressure <=8 mmHg within 30 min (22 and 27 min, respectively). Necropsy findings
      revealed a viable omentum flap and pedicle in both animals, with no evidence of
      procedure-related complications. Angiographic and histological analyses confirmed
      vessel communication between the omentum and the left ventricle. CONCLUSIONS: Our
      TPP approach was shown to be feasible and safe with a low-pressure
      pneumoperitoneum, while the omentum flap was durable. This successful combination
      of techniques may provide less-invasive endoscopic intervention and regenerative
      therapy.

PMID- 29360999
TI  - dsRNA Injection Successfully Inhibited Two Endogenous beta-Glucosidases in
      Coptotermes formosanus (Isoptera: Rhinotermitidae).
AB  - Cellulose digestion is an essential process of termites, and it is accomplished
      by three types of cellulases. beta-Glucosidase (BG), one of the critical
      cellulases responsible for cellulose degradation and glucose production, has been
      considered as a potential target for pest management strategies. Previous
      experiments identified two new endogenous BG homologs, CfBG-Ia and CfBG-Ib, in
      the digestive system of Coptotermes formosanus Shiraki (Isoptera:
      Rhinotermitidae). The objectives of this study were to assess the impact of RNA
      interference on CfBG-Ia and CfBG-Ib expression and on termite survival. We tested
      the expression profiles of worker termites which were injected with gene-specific
      double-stranded RNA (dsRNA, targeting one gene at a time) and a dsRNA cocktail
      (targeting CfBG-Ia and CfBG-Ib simultaneously). The expression of CfBG-Ib showed
      a sharp decline in both dsCfBG-Ib and dsRNA cocktail treatments. The expression
      of CfBG-Ia reduced quickly and significantly in the dsRNA cocktail treatment;
      while in dsCfBG-Ia treatment, it decreased on the fifth day. Results showed that
      treatment with the dsRNA cocktail caused greater inhibition of the transcript
      expression and a shorter response time. However, the expression of nontarget BG
      homologs was increased as the target BG homologs were being repressed during the
      testing period in dsRNA cocktail treatment. These results demonstrate that
      targeting cellulase-coding genes may be a potential strategy to inhibit termite
      digestion process, or at least dsRNA cocktails serve as a means for identifying
      the most susceptible target gene families or biological processes.

PMID- 29361000
TI  - Biological Activity of Bacillus thuringiensis (Bacillales: Bacillaceae) in
      Anastrepha fraterculus (Diptera: Tephritidae).
AB  - Anastrepha fraterculus (Wiedemann) (Diptera: Tephritidae) is considered to be one
      of the major pest insects in fruit orchards worldwide. Bacillus thuringiensis
      Berliner (Bacillales: Bacillaceae) strains are widely used as biological control
      agents and show high biological activity against different insect species. The
      objective of this study was to evaluate the biological activity of different
      strains of B. thuringiensis against A. fraterculus larvae and adults. Bioassays
      were performed using suspensions of bacterial spores/crystals of B. thuringiensis
      var. israelensis (Bti), kurstaki (Btk), and oswaldocruzi (Bto) strains at three
      concentrations [2 * 107, 2 * 108, and 2 * 109 colony-forming units per ml (CFU ml
      1)]. At a concentration of 2 * 109 CFU ml-1, a significant larval effect
      (mortality 60%) was observed when compared with the control treatment. Larvae
      that ingested spore/crystal suspensions of Bti, Btk, or Bto bacterial strains
      exhibited significant larval and pupal deformations, leading to a significant
      decrease (~50%) in the completion of the insects' biological cycle (egg to
      adult). The B. thuringiensis strains (Bti, Btk, or Bto) at a concentration of 2 *
      109 CFU ml-1 in combination with one food attractant (BioAnastrepha 3% or
      CeraTrap 1.5%) in formulations of toxic baits provided high mortality (mortality
      > 85%) of A. fraterculus adults 7 d after treatment. However, the Btk strain in
      combination with CeraTrap 1.5% caused mortality of 40%. On the basis of these
      results, the native bacterial strains Bti, Btk, and Bto were considered to be
      promising candidates as biological control agents against A. fraterculus.

PMID- 29361001
TI  - Cost-effectiveness of Population-Based BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2
      Mutation Testing in Unselected General Population Women.
AB  - Background: The cost-effectiveness of population-based panel testing for high-
      and moderate-penetrance ovarian cancer (OC)/breast cancer (BC) gene mutations is
      unknown. We evaluate the cost-effectiveness of population-based
      BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutation testing compared with clinical
      criteria/family history (FH) testing in unselected general population women.
      Methods: A decision-analytic model comparing lifetime costs and effects of
      criteria/FH-based BRCA1/BRCA2 testing is compared with
      BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing in those fulfilling clinical
      criteria/strong FH of cancer (>=10% BRCA1/BRCA2 probability) and all women age 30
      years or older. Analyses are presented for UK and US populations. Identified
      carriers undergo risk-reducing salpingo-oophorectomy. BRCA1/BRCA2/PALB2 carriers
      can opt for magnetic resonance imaging/mammography, chemoprevention, or risk
      reducing mastectomy. One-way and probabilistic sensitivity analysis (PSA) enabled
      model uncertainty evaluation. Outcomes include OC, BC, and additional heart
      disease deaths. Quality-adjusted life-years (QALYs), OC incidence, BC incidence,
      and incremental cost-effectiveness ratio (ICER) were calculated. The time horizon
      is lifetime and perspective is payer. Results: Compared with clinical criteria/FH
      based BRCA1/BRCA2 testing, clinical criteria/FH-based
      BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is cost-effective (ICER =
      L7629.65/QALY or $49 282.19/QALY; 0.04 days' life-expectancy gained). Population
      based testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 mutations is the most
      cost-effective strategy compared with current policy: ICER = L21 599.96/QALY or
      $54 769.78/QALY (9.34 or 7.57 days' life-expectancy gained). At L30 000/QALY and
      $100 000/QALY willingness-to-pay thresholds, population-based
      BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 panel testing is the preferred strategy in
      83.7% and 92.7% of PSA simulations; criteria/FH-based panel testing is preferred
      in 16.2% and 5.8% of simulations, respectively. Population-based
      BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing can prevent 1.86%/1.91% of BC and
      3.2%/4.88% of OC in UK/US women: 657/655 OC cases and 2420/2386 BC cases
      prevented per million. Conclusions: Population-based
      BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than any
      clinical criteria/FH-based strategy. Clinical criteria/FH-based
      BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 testing is more cost-effective than
      BRCA1/BRCA2 testing alone.

PMID- 29361002
TI  - Aspirin and Risk of Gastric Cancer After Helicobacter pylori Eradication: A
      Territory-Wide Study.
AB  - Background: Despite successful H. pylori (HP) eradication, some individuals
      remain at risk of developing gastric cancer (GC). Previous studies showed that
      aspirin was associated with a reduced GC risk. However, whether aspirin can
      reduce GC risk in HP-eradicated subjects remains unknown. We aimed to determine
      the chemopreventive effect of aspirin in HP-eradicated subjects. Methods: We
      identified subjects who had received a prescription of clarithromycin-based
      triple therapy for HP between 2003 and 2012 from a territory-wide health care
      database. The observation period started from commencement of HP therapy (index
      date), and the follow-up was censored at the end of the study (December 2015),
      death, or GC diagnosis. Aspirin use was defined as use once or more often weekly.
      Subjects who failed HP eradication or were diagnosed with GC within 12 months of
      HP therapy were excluded. The hazard ratio (HR) of GC with aspirin use was
      calculated by Cox model with Propensity Score adjustment for age, sex,
      comorbidities, and concurrent medications. All statistical tests were two-sided.
      Results: The median follow-up was 7.6 years (interquartile range [IQR] = 5.1-10.3
      years), and 169 (0.27%) out of 63 605 patients developed GC. The incidence rate
      of GC was 3.5 per 10 000 person-years. Aspirin use was associated with a reduced
      GC risk (HR = 0.30, 95% confidence interval [CI] = 0.15 to 0.61). The risk of GC
      decreased with increasing frequency, duration, and dose of aspirin (all Ptrend <
      .001). Conclusions: Aspirin use was associated with a frequency-, dose-, and
      duration-dependent reduction in GC risk after HP eradication. The effect was most
      prominent in those who used aspirin daily or for five or more years.

PMID- 29360998
TI  - Concussion, microvascular injury, and early tauopathy in young athletes after
      impact head injury and an impact concussion mouse model.
AB  - The mechanisms underpinning concussion, traumatic brain injury, and chronic
      traumatic encephalopathy, and the relationships between these disorders, are
      poorly understood. We examined post-mortem brains from teenage athletes in the
      acute-subacute period after mild closed-head impact injury and found
      astrocytosis, myelinated axonopathy, microvascular injury, perivascular
      neuroinflammation, and phosphorylated tau protein pathology. To investigate
      causal mechanisms, we developed a mouse model of lateral closed-head impact
      injury that uses momentum transfer to induce traumatic head acceleration.
      Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset,
      transient course, and rapid resolution of a concussion-like syndrome
      characterized by altered arousal, contralateral hemiparesis, truncal ataxia,
      locomotor and balance impairments, and neurobehavioural deficits. Experimental
      impact injury was associated with axonopathy, blood-brain barrier disruption,
      astrocytosis, microgliosis (with activation of triggering receptor expressed on
      myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in
      cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was
      detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and
      distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co
      localized with serum albumin extravasation in the brain that was diagnostically
      detectable in living mice by dynamic contrast-enhanced MRI. These pathologies
      were also accompanied by early, persistent, and bilateral impairment in axonal
      conduction velocity in the hippocampus and defective long-term potentiation of
      synaptic neurotransmission in the medial prefrontal cortex, brain regions distant
      from acute brain injury. Surprisingly, acute neurobehavioural deficits at the
      time of injury did not correlate with blood-brain barrier disruption,
      microgliosis, neuroinflammation, phosphorylated tauopathy, or
      electrophysiological dysfunction. Furthermore, concussion-like deficits were
      observed after impact injury, but not after blast exposure under experimental
      conditions matched for head kinematics. Computational modelling showed that
      impact injury generated focal point loading on the head and seven-fold greater
      peak shear stress in the brain compared to blast exposure. Moreover,
      intracerebral shear stress peaked before onset of gross head motion. By
      comparison, blast induced distributed force loading on the head and diffuse,
      lower magnitude shear stress in the brain. We conclude that force loading
      mechanics at the time of injury shape acute neurobehavioural responses,
      structural brain damage, and neuropathological sequelae triggered by neurotrauma.
      These results indicate that closed-head impact injuries, independent of
      concussive signs, can induce traumatic brain injury as well as early pathologies
      and functional sequelae associated with chronic traumatic encephalopathy. These
      results also shed light on the origins of concussion and relationship to
      traumatic brain injury and its aftermath.awx350media15713427811001.

PMID- 29361003
TI  - Efficacy of Two Systemic Insecticides With Stem Gall Wasp, Zapatella davisae
      (Hymenoptera: Cynipidae) on Black Oak.
AB  - Black oak, Quercus velutina Lamarck, is the dominant deciduous tree on Cape Cod,
      Nantucket, and Martha's Vineyard, Massachusetts, and in recent years it has
      experienced widespread mortality and severe canopy loss due to infestations of a
      stem gall wasp, Zapatella davisae Buffington and Melika (Hymenoptera: Cynipidae).
      A single application of systemic insecticides emamectin benzoate and imidacloprid
      was found to reduce or prevent further accumulation of Z. davisae damage on
      infested black oak during a 1-yr trial.

PMID- 29361004
TI  - It is time to give social research a voice to tackle antimicrobial resistance?

PMID- 29361005
TI  - Influence of Birth Cohort on Effectiveness of 2015-2016 Influenza Vaccine Against
      Medically Attended Illness Due to 2009 Pandemic Influenza A(H1N1) Virus in the
      United States.
AB  - Background: The effectiveness of influenza vaccine during 2015-2016 was reduced
      in some age groups as compared to that in previous 2009 pandemic influenza
      A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the
      age at first exposure to specific influenza A(H1N1) viruses could influence
      vaccine effectiveness (VE). Methods: We estimated the effectiveness of influenza
      vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09
      associated medically attended illness from the 2010-2011 season through the 2015
      2016 season, according to patient birth cohort using data from the Influenza
      Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis
      of likely immunologic priming with groups of influenza A(H1N1) viruses that
      circulated during 1918-2015. VE was calculated as 100 * [1 - adjusted odds ratio]
      from logistic regression models comparing the odds of vaccination among influenza
      virus-positive versus influenza test-negative patients. Results: A total of 2115
      A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged >=6
      months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against
      A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons,
      compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016,
      A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958
      1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined.
      Conclusion: Findings suggest an association between reduced VE against influenza
      A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific
      influenza A(H1N1) viruses.

PMID- 29361006
TI  - Pediatric Chordomas: Results of a Multicentric Study of 40 Children and Proposal
      for a Histopathological Prognostic Grading System and New Therapeutic Strategies.
AB  - Pediatric chordomas are rare malignant neoplasms, and few data are available for
      optimizing therapeutic strategies and outcome. This study aimed at evaluating how
      best to manage them and to identify prognostic factors. This multicentric
      retrospective study included 40 children diagnosed with chordomas between 1966
      and 2012. Clinical, radiological, and histopathological data, treatment
      modalities, and outcomes were reviewed. The median age was 12 years old. Most
      chordomas were histologically classical forms (45.5%) and were mostly located at
      the skull base (72.5%). The overall survival (OS) was 66.6% and 58.6%, and
      progression-free survival (PFS) was 55.7% and 52% at 5 and 10 years,
      respectively. Total resection was correlated with a better outcome (p = 0.04 for
      OS and PFS, log-rank). A histopathological/immunohistochemical grading system
      recently crafted for adults was applied. In a multivariate analysis, it
      significantly correlated with outcome (PFS and OS, p = 0.004), and the loss of
      BAF47 immunoexpression appeared to be a significant independent prognostic factor
      (PFS, p = 0.033). We also identified clinical and histopathological parameters
      that correlated with prognosis. A new grading system combined with the quality of
      surgical resection could help classify patients to postpone radiotherapy in case
      of low risk. Targeted therapy and reirradiation at recurrence may be considered
      as potential therapeutic strategies.

PMID- 29361007
TI  - Design of an Attractant for Empoasca onukii (Hemiptera: Cicadellidae) Based on
      the Volatile Components of Fresh Tea Leaves.
AB  - The tea leafhopper, Empoasca onukii Matsuda, is a serious pest of the tea plant.
      E. onukii prefers to inhabit vigorously growing tender tea leaves. The host
      selection of E. onukii adults may be associated with plant volatile compounds
      (VOCs). We sought to identify potentially attractive VOCs from tea leaves at
      three different ages and test the behavioral responses of E. onukii adults to
      synthetic VOC blends in the laboratory and field to aid in developing an E.
      onukii adult attractant. In darkness, the fresh or mature tea leaves of less than
      1-mo old could attract more leafhoppers than the mature branches (MB) that had
      many older leaves (leaf age >1 mo). Volatile analysis showed that the VOC
      composition of the fresh leaves was the same as that of the mature leaves, but
      linalool and indole were not at detectable levels in VOCs from the MB. Moreover,
      the mass ratio differed for each common volatile in the three types of tea
      leaves. When under competition with volatiles from the MB, the leafhoppers showed
      no significant tropism to each single volatile but could be attracted by the
      synthetic volatile blend imitating the fresh leaves. With the removal of some
      volatile components, the effective synthetic volatile blend was mixed with (Z)-3
      hexen-1-ol, (Z)-3-hexenyl acetate, and linalool at a mass ratio of 0.6:23:12.6.
      These three volatiles may be the key components for the host selection of E.
      onukii adults and could be used as an attractant in tea gardens.

PMID- 29361009
TI  - Erratum.

PMID- 29361008
TI  - The Value of Helicobacter Eradication in Long-term Aspirin Users.

PMID- 29361010
TI  - Pest Prevalence and Evaluation of Community-Wide Integrated Pest Management for
      Reducing Cockroach Infestations and Indoor Insecticide Residues.
AB  - Pest infestations in residential buildings are common, but community-wide pest
      survey data are lacking. Frequent insecticide applications for controlling indoor
      pests leave insecticide residues and pose potential health risks to residents. In
      this study, a community-wide pest survey was carried out in a housing complex
      consisting of 258 units in 40 buildings in New Brunswick, New Jersey. It was
      immediately followed by implementation of an integrated pest management (IPM)
      program in all the cockroach-infested apartments and two bed bug apartments with
      the goal of eliminating pest infestations, reducing pyrethroid residues, and
      increasing resident satisfaction with pest control services. The IPM-treated
      apartments were revisited and treated biweekly or monthly for 7 mo. Initial
      inspection found the top three pests and their infestation rates to be as
      follows: German cockroaches (Blattella germanica L. [Blattodea: Blattellidae]),
      28%; rodents, 11%; and bed bugs (Cimex lectularius L. [Hemiptera: Cimicidae]),
      8%. Floor wipe samples were collected in the kitchens and bedrooms of 20
      apartments for pyrethroid residue analysis before the IPM implementation; 17 of
      the 20 apartments were resampled again at 7 mo. The IPM program reduced cockroach
      counts per apartment by 88% at 7 wk after initial treatment. At 7 mo, 85% of the
      cockroach infestations found in the initial survey were eliminated. The average
      number of pyrethroids detected decreased significantly from 6 +/- 1 (mean +/-
      SEM) and 5 +/- 1 to 2 +/- 1 and 3 +/- 1 in the kitchens and bedrooms,
      respectively. The average concentrations of targeted pyrethroids residue also
      decreased significantly in the kitchens and bedrooms.

PMID- 29361011
TI  - A New Species of the Simulium (Simulium) striatum Species Group (Diptera:
      Simuliidae) from Thailand, and Its Differentiation from Two Related Species Based
      on a Fast-Evolving Nuclear Gene.
AB  - Simulium (Simulium) phraense sp. nov. (Diptera: Simuliidae) is described from
      females, males, pupae, and larvae from Thailand. This new species is placed in
      the Simulium striatum species group and is most similar to Simulium (Simulium)
      nakhonense Takaoka & Suzuki (Diptera: Simuliidae) from Thailand among species of
      the same species group but is barely distinguished from the latter species by
      lacking annular ridges on the surface of the pupal gill filaments. The fast
      evolving nuclear big zinc finger (BZF) gene has successfully differentiated this
      new species from its allies, S. (S.) nakhonense and Simulium (Simulium)
      chiangmaiense Takaoka & Suzuki (Diptera: Simuliidae) of the S. striatum species
      group. The BZF gene sequences show that this new species is more closely related
      to S. (S.) nakhonense than to S. (S.) chiangmaiense, further supporting its
      morphological classification.

PMID- 29361012
TI  - Supplements to Help Prevent Neuropathy During Chemotherapy? A Cautionary Tale.

PMID- 29361013
TI  - The Effects of the Insect Growth Regulators Methoxyfenozide and Pyriproxyfen and
      the Acaricide Bifenazate on Honey Bee (Hymenoptera: Apidae) Forager Survival.
AB  - The honey bee (Apis mellifera L. (Hymenoptera: Apidae)) contributes an essential
      role in the U.S. economy by pollinating major agricultural crops including
      almond, which depends entirely on honey bee pollination for successful nut set.
      Almond orchards are often treated with pesticides to control a variety of pests
      and pathogens, particularly during bloom. While the effects to honey bee health
      of some insecticides, particularly neonicotinoids, have received attention
      recently, the impact of other types of insecticides on honey bee health is less
      clear. In this study, we examined the effects to honey bee forager survival of
      three non-neonicotinoid pesticides widely used during the 2014 California almond
      bloom. We collected foragers from a local apiary and exposed them to three
      pesticides at the label dose, or at doses ranging from 0.5 to 3 times the label
      dose rate. The selected pesticides included the insect growth regulators
      methoxyfenozide and pyriproxyfen, and the acaricide bifenazate. We simulated
      field exposure of honey bees to these pesticides during aerial application in
      almond orchards by using a wind tunnel and atomizer set up with a wind speed of
      2.9 m/s. Experimental groups consisting of 30-40 foragers each were exposed to
      either untreated controls or pesticide-laden treatments and were monitored every
      24 hr over a 10-d period. Our results revealed a significant negative effect of
      all pesticides tested on forager survival. Therefore, we suggest increased
      caution in the application of these pesticides in almond orchards or any
      agricultural crop during bloom to avoid colony health problems.

PMID- 29361014
TI  - The assembly mechanism of coiled-coil domains of the yeast cargo receptors
      Emp46p/47p and the mutational alteration of pH-dependency of complex formation.
AB  - The coiled-coil domains of the putative yeast cargo receptors Emp46p and Emp47p
      are responsible for their complex-formation in the Endoplasmic Reticulum. In
      vitro experiments using coiled-coil domains (Emp46pcc/47pcc) have indicated that
      formation of the hetero-complex is pH-dependent and that amino acid Glu303 of
      Emp46pcc is a key residue in this process. In this study, we investigated the
      effects of various mutations on complex formation and discovered the mechanism
      for its pH-dependency, which is that dissociation of the complex at low pH arises
      mainly from stabilization of Emp46pcc itself. Moreover, destabilization by the
      introduction of a histidine residue in Emp46pcc to repel a lysine residue in
      Emp47pcc, caused an upward shift in the pH profile of complex formation. Another
      mutation in Emp46pcc, a proline to an alanine (P291A), increased the stability of
      the helical structure, especially at low pH and shifted the transition pH upward.
      Combination of these pH-shifting mutations had an additive effect on the pH
      profile of complex formation. Thus, we successfully constructed coiled-coils that
      can react to a wide range of pH, encompassing more appropriate values for use in
      sensing physiological pH changes in the cell.

PMID- 29361016
TI  - The Influence of Reported Penicillin Allergy.

PMID- 29361015
TI  - The Impact of a Reported Penicillin Allergy on Surgical Site Infection Risk.
AB  - Background: A reported penicillin allergy may compromise receipt of recommended
      antibiotic prophylaxis intended to prevent surgical site infections (SSIs). Most
      patients with a reported penicillin allergy are not allergic. We determined the
      impact of a reported penicillin allergy on the development of SSIs. Methods: In
      this retrospective cohort study of Massachusetts General Hospital hip
      arthroplasty, knee arthroplasty, hysterectomy, colon surgery, and coronary artery
      bypass grafting patients from 2010 to 2014, we compared patients with and without
      a reported penicillin allergy. The primary outcome was an SSI, as defined by the
      Centers for Disease Control and Prevention's National Healthcare Safety Network.
      The secondary outcome was perioperative antibiotic use. Results: Of 8385 patients
      who underwent 9004 procedures, 922 (11%) reported a penicillin allergy, and 241
      (2.7%) had an SSI. In multivariable logistic regression, patients reporting a
      penicillin allergy had increased odds (adjusted odds ratio, 1.51; 95% confidence
      interval, 1.02-2.22) of SSI. Penicillin allergy reporters were administered less
      cefazolin (12% vs 92%; P < .001) and more clindamycin (49% vs 3%; P < .001),
      vancomycin (35% vs 3%; P < .001), and gentamicin (24% vs 3%; P < .001) compared
      with those without a reported penicillin allergy. The increased SSI risk was
      entirely mediated by the patients' receipt of an alternative perioperative
      antibiotic; between 112 and 124 patients with reported penicillin allergy would
      need allergy evaluation to prevent 1 SSI. Conclusions: Patients with a reported
      penicillin allergy had a 50% increased odds of SSI, attributable to the receipt
      of second-line perioperative antibiotics. Clarification of penicillin allergies
      as part of routine preoperative care may decrease SSI risk.

PMID- 29361018
TI  - A Diffuse Fine Papular and Pustular Rash in a Man With Advanced Human
      Immunodeficiency Virus and Diabetes.

PMID- 29361019
TI  - A Diffuse Fine Papular and Pustular Rash in a Man With Advanced Human
      Immunodeficiency Virus and Diabetes.

PMID- 29361020
TI  - Blends of Pheromones, With and Without Host Plant Volatiles, Can Attract Multiple
      Species of Cerambycid Beetles Simultaneously.
AB  - Pheromone components of cerambycid beetles are often conserved, with a given
      compound serving as a pheromone component for multiple related species, including
      species native to different continents. Consequently, a single synthesized
      compound may attract multiple species to a trap simultaneously. Furthermore, our
      previous research in east-central Illinois had demonstrated that pheromones of
      different species can be combined to attract an even greater diversity of
      species. Here, we describe the results of field bioassays in the northeastern,
      midwestern, southeastern, south-central, and southwestern United States that
      assessed attraction of cerambycids to a 'generic' pheromone blend containing six
      known cerambycid pheromone components, versus the individual components of the
      blend, and how attraction was influenced by plant volatiles. Nineteen species
      were attracted in significant numbers, with the pheromone blend attracting about
      twice as many species as any of the individual components. The blend attracted
      species of three subfamilies, whereas individual components attracted species
      within one subfamily. However, some antagonistic interactions between blend
      components were identified. The plant volatiles ethanol and alpha-pinene usually
      enhanced attraction to the blend. Taken together, these experiments suggest that
      blends of cerambycid pheromones, if selected carefully to minimize inhibitory
      effects, can be effective for sampling a diversity of species, and that plant
      volatiles generally enhance attraction. Such generic pheromone blends may serve
      as an effective and economical method of detecting incursions of exotic,
      potentially invasive species.

PMID- 29361021
TI  - Closing in on the Reservoir: Proactive Case Detection in High-Risk Groups as a
      Strategy to Detect Plasmodium falciparum Asymptomatic Carriers in Cambodia.
AB  - Background: In the frame of elimination strategies of Plasmodium falciparum (Pf),
      active case detection has been recommended as complementary approach to the
      existing passive case detection programs. We trialed a polymerase chain reaction
      (PCR)-based active detection strategy targeting asymptomatic individuals, named
      proactive case detection (PACD), with the aim of assessing its feasibility, the
      extra yield of Pf infections, and the at-risk population for Pf carriage status.
      Methods: A pilot of PACD was conducted in 3 villages in Chey Saen district (Preah
      Vihear province, Cambodia), from December 2015 to March 2016. Voluntary screening
      and treatment, following health promotion sensitization, was used as mobilization
      strategy. Results: A total of 2802 persons were tested, representing 54% of the
      population. PACD (n = 30) and the respective reactive case detection (RACD) (n =
      3) identified 33 Pf carriers, approximately twice as many as the Pf infections (n
      = 17) diagnosed in passive case detection and respective RACD, by health centers
      and village malaria workers using PCR, in the same villages/period. Final
      positivity rate was 1.07% (30/2802). People spending nighttime in forests and
      plantations were found to be at increased risk for Pf infection (odds ratio [OR],
      3.4 [95% CI, 1.6-7.2], P = .002 and OR, 2.3 [95% CI, 1.1-4.9], P = .03,
      respectively). Conclusions: We demonstrated the usefulness of the PACD component
      in identifying Pf asymptomatic carriers. Social mobilization and promotion led to
      good attendance of specific risk groups, identified to be, in the Cambodian
      context, individuals spending nighttime in forest and plantations.

PMID- 29361022
TI  - Multiple sclerosis risk variants alter expression of co-stimulatory genes in B
      cells.
AB  - The increasing evidence supporting a role for B cells in the pathogenesis of
      multiple sclerosis prompted us to investigate the influence of known
      susceptibility variants on the surface expression of co-stimulatory molecules in
      these cells. Using flow cytometry we measured surface expression of CD40 and CD86
      in B cells from 68 patients and 162 healthy controls that were genotyped for the
      multiple sclerosis associated single nucleotide polymorphisms (SNPs) rs4810485,
      which maps within the CD40 gene, and rs9282641, which maps within the CD86 gene.
      We found that carrying the risk allele rs4810485*T lowered the cell-surface
      expression of CD40 in all tested B cell subtypes (in total B cells P <= 5.10 * 10
      5 in patients and <=4.09 * 10-6 in controls), while carrying the risk allele
      rs9282641*G increased the expression of CD86, with this effect primarily seen in
      the naive B cell subset (P = 0.048 in patients and 5.38 * 10-5 in controls). In
      concordance with these results, analysis of RNA expression demonstrated that the
      risk allele rs4810485*T resulted in lower total CD40 expression (P = 0.057) but
      with an increased proportion of alternative splice-forms leading to decoy
      receptors (P = 4.00 * 10-7). Finally, we also observed that the risk allele
      rs4810485*T was associated with decreased levels of interleukin-10 (P = 0.020),
      which is considered to have an immunoregulatory function downstream of CD40.
      Given the importance of these co-stimulatory molecules in determining the immune
      reaction that appears in response to antigen our data suggest that B cells might
      have an important antigen presentation and immunoregulatory role in the
      pathogenesis of multiple sclerosis.

PMID- 29361023
TI  - Corrigendum to: Identification of capillary rarefaction using intracoronary wave
      intensity analysis with resultant prognostic implications for cardiac allograft
      patients.

PMID- 29361024
TI  - Commentary on: Hypochlorous Acid Versus Povidone-Iodine Containing Irrigants:
      Which Antiseptic Is More Effective for Breast Implant Pocket Irrigation?

PMID- 29361026
TI  - On the Relationship between Medical Ethics and the Law.
AB  - In his comments on Bland, Lord Justice Hoffmann stated that 'I would expect
      medical ethics to be formed by the law rather than the reverse'. But what judges
      expect, and what they have a right to expect, are different things; I shall use
      Hoffmann LJ's statement as a way into looking at the relationship between ethics
      and law, and argue that it is partially correct insofar as that it makes a
      prediction about that relationship. Professional ethics and codes of ethics are
      shaped by law; but law is shaped by those codes to some extent, and both are
      influenced by 'philosophical ethics'. As a normative claim, Hoffmann LJ's
      statement is more compelling; but he also distinguished between 'medical ethics'
      and 'morality', and this merits exploration. There remains a question about the
      proper relationship between law, ethics, and morality that I shall address.

PMID- 29361025
TI  - Estimating Time to the Common Ancestor for a Beneficial Allele.
AB  - The haplotypes of a beneficial allele carry information about its history that
      can shed light on its age and the putative cause for its increase in frequency.
      Specifically, the signature of an allele's age is contained in the pattern of
      variation that mutation and recombination impose on its haplotypic background. We
      provide a method to exploit this pattern and infer the time to the common
      ancestor of a positively selected allele following a rapid increase in frequency.
      We do so using a hidden Markov model which leverages the length distribution of
      the shared ancestral haplotype, the accumulation of derived mutations on the
      ancestral background, and the surrounding background haplotype diversity. Using
      simulations, we demonstrate how the inclusion of information from both mutation
      and recombination events increases accuracy relative to approaches that only
      consider a single type of event. We also show the behavior of the estimator in
      cases where data do not conform to model assumptions, and provide some
      diagnostics for assessing and improving inference. Using the method, we analyze
      population-specific patterns in the 1000 Genomes Project data to estimate the
      timing of adaptation for several variants which show evidence of recent selection
      and functional relevance to diet, skin pigmentation, and morphology in humans.

PMID- 29361027
TI  - Extended-spectrum beta-lactamase-producing Escherichia coli contributes to the
      survival of cefotaxime-susceptible E. coli under high concentrations of
      cefotaxime by acquisition of increased AmpC expression.
AB  - Extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E) are becoming
      increasingly widespread in Vietnam. Antibiotics are detected in many Vietnamese
      foods; however, the effect of ESBL-E and antibiotic consumption on intestinal
      bacteria has not been studied sufficiently. Here, we investigated the effect of
      oral administration of ESBL-E (TB19) and cefotaxime on luminescence-emitting
      cefotaxime-sensitive E. coli (X14). Mice were given water containing TB19 and
      then received three injections of 1.0 * 108 CFU of X14 harboring a luciferase
      gene. The mice were administered 100 MUg of cefotaxime and luminescent bacteria
      were monitored over 24 h, following which luminescent bacteria were isolated from
      mouse feces. Luminescence continued to be detected in mice administered TB19 24 h
      after cefotaxime ingestion. Fecal analysis revealed two types of luminescent
      colonies: cefoxitin-resistant E. coli (X14-R) and Pseudomonas aeruginosa. Pulse
      field gel electrophoresis confirmed that X14-R was a clonal strain of X14,
      suggesting that X14 survived using ESBLs originating from TB19 and acquired
      cefoxitin resistance due to cefotaxime consumption. Moreover, in vitro analysis
      of X14 indicated that expression of the ampC gene was upregulated by cefotaxime.
      Overall, ESBL-E and cefotaxime promoted the expansion of cefoxitin-resistant E.
      coli in the absence of plasmid-mediated gene transfer.

PMID- 29361028
TI  - Structural and functional analysis of ribosome assembly factor Efg1.
AB  - Ribosome biogenesis in eukaryotes is a complicated process that involves
      association and dissociation of numerous assembly factors and snoRNAs. The yeast
      small ribosomal subunit is first assembled into 90S pre-ribosomes in an ordered
      and dynamic manner. Efg1 is a protein with no recognizable domain that is
      associated with early 90S particles. Here, we determine the crystal structure of
      Efg1 from Chaetomium thermophilum at 3.3 A resolution, revealing a novel
      elongated all-helical structure. Efg1 is not located in recently determined cryo
      EM densities of 90S likely due to its low abundance in mature 90S. Genetic
      analysis in Saccharomyces cerevisiae shows that the functional core of Efg1
      contains two helical hairpins composed of highly conserved residues. Depletion of
      Efg1 blocks 18S rRNA processing at sites A1 and A2, but not at site A0, and
      production of small ribosomal subunits. Efg1 is initially recruited by the 5'
      domain of 18S rRNA. Its absence disturbs the assembly of the 5' domain and
      inhibits release of U14 snoRNA from 90S. Our study shows that Efg1 is required
      for early assembly and reorganization of the 5' domain of 18S rRNA.

PMID- 29361029
TI  - The Pros and Cons of the PROs.

PMID- 29361030
TI  - Epigenetic features of human telomeres.
AB  - Although subtelomeric regions in humans are heterochromatic, the epigenetic
      nature of human telomeres remains controversial. This controversy might have been
      influenced by the confounding effect of subtelomeric regions and interstitial
      telomeric sequences (ITSs) on telomeric chromatin structure analyses. In
      addition, different human cell lines might carry diverse epigenetic marks at
      telomeres. We have developed a reliable procedure to study the chromatin
      structure of human telomeres independently of subtelomeres and ITSs. This
      procedure is based on the statistical analysis of multiple ChIP-seq experiments.
      We have found that human telomeres are not enriched in the heterochromatic
      H3K9me3 mark in most of the common laboratory cell lines, including embryonic
      stem cells. Instead, they are labeled with H4K20me1 and H3K27ac, which might be
      established by p300. These results together with previously published data argue
      that subtelomeric heterochromatin might control human telomere functions.
      Interestingly, U2OS cells that exhibit alternative lengthening of telomeres have
      heterochromatic levels of H3K9me3 in their telomeres.

PMID- 29361031
TI  - The cohesion establishment factor Esco1 acetylates alpha-tubulin to ensure proper
      spindle assembly in oocyte meiosis.
AB  - Esco1 has been reported to function as a cohesion establishment factor that
      mediates chromosome cohesion and segregation in mitotic cells. However, its exact
      roles in meiosis have not been clearly defined. Here, we document that Esco1 is
      expressed and localized to both the nucleus and cytoplasm during mouse oocyte
      meiotic maturation. Depletion of Esco1 by siRNA microinjection causes the meiotic
      progression arrest with a severe spindle abnormality and chromosome misalignment,
      which is coupled with a higher incidence of the erroneous kinetochore-microtubule
      attachments and activation of spindle assembly checkpoint. In addition, depletion
      of Esco1 leads to the impaired microtubule stability shown by the weakened
      resistance ability to the microtubule depolymerizing drug nocodazole and the
      decreased level of acetylated alpha-tubulin. Conversely, overexpression of Esco1
      causes hyperacetylation of alpha-tubulin and spindle defects. Moreover, we find
      that Esco1 binds to alpha-tubulin and is required for its acetylation. The
      reduced acetylation level of alpha-tubulin in Esco1-depleted oocytes can be
      restored by the ectopic expression of exogenous wild-type Esco1 but not
      enzymatically dead Esco1-G768D. Purified wild-type Esco1 instead of mutant Esco1
      G768D acetylates the synthesized peptide of alpha-tubulin in vitro. Collectively,
      our data assign a novel function to Esco1 as a microtubule regulator during
      oocyte meiotic maturation beyond its conventional role in chromosome cohesion.

PMID- 29361032
TI  - Post-silking carbon partitioning under nitrogen deficiency revealed sink
      limitation of grain yield in maize.
AB  - Maize (Zea mays) plants exhibit altered carbon partitioning under nitrogen (N)
      deficiency, but the mechanisms by which N availability affects sugar export out
      of leaves and transport into developing ears remain unclear. Maize was grown
      under field conditions with different N supply. Plant growth, sugar movement, and
      starch turnover in source or sink tissues were investigated at silking and 20 or
      21 days after silking. Nitrogen deficiency stunted plant growth and grain yield
      compared with N-sufficient plants, and resulted in greater starch concentrations
      in leaves due to more as well as larger starch granules in bundle sheath cells.
      Transmission electron microscopy revealed an open symplastic pathway for sucrose
      movement in N-deficient leaves, while the expression levels of transporters
      responsible for sucrose efflux and phloem loading were lower than in N-sufficient
      leaves. Nonetheless, greater starch concentrations in the apical cob portion of N
      deficient plants implied sufficient carbon supply relative to the diminished sink
      strength (decreased kernel number and weight). Together with the high sugar
      concentrations in the developing kernels, the results indicated that reduced sink
      capacity and sugar utilization during grain filling may limit the yield in N
      deficient plants, which in turn imposes a feedback inhibition on sugar export
      from leaves.

PMID- 29361033
TI  - Single-particle trajectories reveal two-state diffusion-kinetics of hOGG1
      proteins on DNA.
AB  - We reanalyze trajectories of hOGG1 repair proteins diffusing on DNA. A previous
      analysis of these trajectories with the popular mean-squared-displacement
      approach revealed only simple diffusion. Here, a new optimal estimator of
      diffusion coefficients reveals two-state kinetics of the protein. A simple,
      solvable model, in which the protein randomly switches between a loosely bound,
      highly mobile state and a tightly bound, less mobile state is the simplest
      possible dynamic model consistent with the data. It yields accurate estimates of
      hOGG1's (i) diffusivity in each state, uncorrupted by experimental errors arising
      from shot noise, motion blur and thermal fluctuations of the DNA; (ii) rates of
      switching between states and (iii) rate of detachment from the DNA. The protein
      spends roughly equal time in each state. It detaches only from the loosely bound
      state, with a rate that depends on pH and the salt concentration in solution,
      while its rates for switching between states are insensitive to both. The
      diffusivity in the loosely bound state depends primarily on pH and is three to
      ten times higher than in the tightly bound state. We propose and discuss some new
      experiments that take full advantage of the new tools of analysis presented here.

PMID- 29361034
TI  - Exploring DNA variant segregation types in pooled genome sequencing enables
      effective mapping of weeping trait in Malus.
AB  - To unlock the power of next generation sequencing-based bulked segregant analysis
      in allele discovery in out-crossing woody species, and to understand the genetic
      control of the weeping trait, an F1 population from the cross 'Cheal's Weeping' *
      'Evereste' was used to create two genomic DNA pools 'weeping' (17 progeny) and
      'standard' (16 progeny). Illumina pair-end (2 * 151 bp) sequencing of the pools
      to a 27.1* (weeping) and a 30.4* (standard) genome (742.3 Mb) coverage allowed
      detection of 84562 DNA variants specific to 'weeping', 92148 specific to
      'standard', and 173169 common to both pools. A detailed analysis of the DNA
      variant genotypes in the pools predicted three informative segregation types of
      variants: <lm*mm> (type I) in weeping pool-specific variants, and <lm*ll> (type
      II) and <hk*hk> (type III) in variants common to both pools, where the first
      allele is assumed to be weeping linked and the allele shown in bold is a variant
      in relation to the reference genome. Conducting variant allele frequency and
      density-based mappings revealed four genomic regions with a significant
      association with weeping: a major locus, Weeping (W), on chromosome 13 and others
      on chromosomes 10 (W2), 16 (W3), and 5 (W4). The results from type I variants
      were noisier and less certain than those from type II and type III variants,
      demonstrating that although type I variants are often the first choice, type II
      and type III variants represent an important source of DNA variants that can be
      exploited for genetic mapping in out-crossing woody species. Confirmation of the
      mapping of W and W2, investigation into their genetic interactions, and
      identification of expressed genes in the W and W2 regions provided insight into
      the genetic control of weeping and its expressivity in Malus.

PMID- 29361036
TI  - Prognostic Significance of Pre-Operative Monocyte-to-Lymphocyte Ratio in Lung
      Cancer Patients Undergoing Radical Surgery.
AB  - Background: Inflammatory response is known to play a vital role in carcinogenesis
      and cancer progression. The prognostic relevance of monocyte-to-lymphocyte ratio
      (MLR), as a biomarker of inflammatory response has been demonstrated in patients
      with hematologic cancers. Objectives: In this study, we assessed the prognostic
      relevance of MLR in patients with resectable lung carcinoma. Methods: Clinical
      records of 705 lung cancer patients who underwent radical resection at our
      hospital between October 2006 and January 2011 were retrospectively reviewed. The
      optimal cutoff value of MLR as a prognostic indicator was determined on receiver
      operating characteristic curve analysis. Results: On multivariate analysis using
      Cox proportional hazards regression model, MLR was an independent predictor of
      both overall survival (hazard ratio [HR] 1.494, 95% confidence interval [CI]
      1.158-1.927, P = .002) and disease-free survival (HR 1.547, 95% CI 1.172-2.043, P
      = .002). Conclusions: Preoperative MLR may be a simple, reliable prognostic
      marker for risk stratification and be used to guide treatment decision-making in
      lung cancer patients.

PMID- 29361035
TI  - WOX11 recruits a histone H3K27me3 demethylase to promote gene expression during
      shoot development in rice.
AB  - WUSCHEL-related homeobox (WOX) genes are key regulators of meristem activity and
      plant development, the chromatin mechanism of which to reprogram gene expression
      remains unclear. Histone H3K27me3 is a chromatin mark of developmentally
      repressed genes. How the repressive mark is removed from specific genes during
      plant development is largely unknown. Here, we show that WOX11 interacts with the
      H3K27me3 demethylase JMJ705 to activate gene expression during shoot development
      in rice. Genetic analysis indicates that WOX11 and JMJ705 cooperatively control
      shoot growth and commonly regulate the expression of a set of genes involved in
      meristem identity, chloroplast biogenesis, and energy metabolism in the shoot
      apex. Loss of WOX11 led to increased H3K27me3 and overexpression of JMJ705
      decreased the methylation levels at a subset of common targets. JMJ705 is
      associated with most of the WOX11-binding sites found in the tested common
      targets in vivo, regardless of presence or absence of the JMJ705-binding motif.
      Furthermore, wox11 mutation reduced JMJ705-binding to many targets genome-wide.
      The results suggest that recruitment of JMJ705 to specific developmental pathway
      genes is promoted by DNA-binding transcription factors and that WOX11 functions
      to stimulate shoot growth through epigenetic reprogramming of genes involved in
      meristem development and energy-generating pathways.

PMID- 29361037
TI  - JPP Student Journal Club Commentary: Linking Biology to the Environment: Novel
      Methods for Understanding Pediatric Obesity.

PMID- 29361038
TI  - Cold-inducible RNA-binding protein (CIRP) induces translation of the cell-cycle
      inhibitor p27Kip1.
AB  - The CDK inhibitor p27Kip1 plays a central role in controlling cell proliferation
      and cell-cycle exit. p27Kip1 protein levels oscillate during cell-cycle
      progression and are regulated by mitogen or anti-proliferative signaling. The
      abundance of the protein is frequently determined by post-transcriptional
      mechanisms including ubiquitin-mediated proteolysis and translational control.
      Here, we report that the cold-inducible RNA-binding protein (CIRP) selectively
      binds to the 5' untranslated region of the p27Kip1 mRNA. CIRP is induced,
      modified and relocalized in response to various stress stimuli and can regulate
      cell survival and cell proliferation particularly during stress. Binding of CIRP
      to the 5'UTR of the p27Kip1 mRNA significantly enhanced reporter translation. In
      cells exposed to mild hypothermia, the induction of CIRP correlated with
      increased translation of a p27Kip1 5'UTR reporter and with the accumulation of
      p27Kip1 protein. shRNA-mediated CIRP knockdown could prevent the induction of
      translation. We found that p27Kip1 is central for the decreased proliferation at
      lower temperature, since p27Kip1 KO mouse embryonic fibroblasts (MEFs) hardly
      increased their doubling time in hypothermic conditions, whereas wild-type MEFs
      significantly delayed proliferation in response to cold stress. This suggests
      that the CIRP-dependent p27Kip1 upregulation during mild hypothermia contributes
      to the cold shock-induced inhibition of cell proliferation.

PMID- 29361039
TI  - Structure-activity relationships and cellular mechanism of action of small
      molecules that enhance the delivery of oligonucleotides.
AB  - The pharmacological effects of antisense and siRNA oligonucleotides are hindered
      by the tendency of these molecules to become entrapped in endomembrane
      compartments thus failing to reach their targets in the cytosol or nucleus. We
      have previously used high throughput screening to identify small molecules that
      enhance the escape of oligonucleotides from intracellular membrane compartments
      and have termed such molecules OECs (oligonucleotide enhancing compounds). Here,
      we report on the structure-activity relationships of a family of OECs that are
      analogs of a hit that emerged from our original screen. These studies demonstrate
      key roles for the lipophilic aromatic groups, the tertiary nitrogen, and the
      carbamate moiety of the parent compound. We have also investigated the
      intracellular site of action of the OECs and have shown that activity is due to
      the release of oligonucleotides from intermediate endosomal compartments rather
      than from early endosomes or from highly acidic downstream compartments. At high
      concentrations of OECs toxicity occurs in a manner that is independent of
      caspases or of lysosomal cathepsins but instead involves increased plasma
      membrane permeability. Thus, in addition to describing specific characteristics
      of this family of OECs, the current study provides insights into basic mechanisms
      of oligonucleotide trafficking and their implications for oligonucleotide
      delivery.

PMID- 29361040
TI  - Highly selective retrieval of accurate DNA utilizing a pool of in situ-replicated
      DNA from multiple next-generation sequencing platforms.
AB  - Scalable and cost-effective production of error-free DNA is critical to meet the
      increased demand for such DNA in the field of biological science. Methods based
      on 'Dial-out PCR' have enabled the high-throughput error-free DNA synthesis from
      a microarray-synthesized DNA pool by labeling with retrieval PCR tags, and
      retrieving error-free DNA of which the sequence is identified via next generation
      sequencing (NGS). However, most of the retrieved products contain byproducts due
      to background amplification of redundantly labeled DNAs. Here, we present a
      highly selective retrieval method of desired DNA from a pool of millions of DNA
      clones from NGS platforms. Our strategy is based on replicating entire sequence
      verified DNA molecules from NGS plates to obtain population-controlled DNA pool.
      Using the NGS-replica pool, we could perform improved and selective retrieval of
      desired DNA from the replicated DNA pool compared to other dial-out PCR based
      methods. To evaluate the method, we tested this strategy by using 454, Illumina,
      and Ion Torrent platforms for producing NGS-replica pool. As a result, we
      observed a highly selective retrieval yield of over 95%. We anticipate that
      applications based on this method will enable the preparation of high-fidelity
      sequenced DNA from heterogeneous collections of DNA molecules.

PMID- 29361041
TI  - The human cytomegalovirus terminase complex as an antiviral target: a close-up
      view.
AB  - Human cytomegalovirus (HCMV) is responsible for life-threatening infections in
      immunocompromised individuals and can cause serious congenital malformations.
      Available antivirals target the viral polymerase but are subject to cross
      resistance and toxicity. New antivirals targeting other replication steps and
      inducing fewer adverse effects are therefore needed. During HCMV replication, DNA
      maturation and packaging are performed by the terminase complex, which cleaves
      DNA to package the genome into the capsid. Identified in herpesviruses and
      bacteriophages, and with no counterpart in mammalian cells, these terminase
      proteins are ideal targets for highly specific antivirals. A new terminase
      inhibitor, letermovir, recently proved effective against HCMV in phase III
      clinical trials, but the mechanism of action is unclear. Letermovir has no
      significant activity against other herpesvirus or non-human CMV. This review
      focuses on the highly conserved mechanism of HCMV DNA-packaging and the potential
      of the terminase complex to serve as an antiviral target. We describe the
      intrinsic mechanism of DNA-packaging, highlighting the structure-function
      relationship of HCMV terminase complex components.

PMID- 29361042
TI  - Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized
      Trial of Acetyl-L-Carnitine (SWOG S0715).
AB  - Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and
      disabling side effect of taxanes. Acetyl-L-carnitine (ALC) was unexpectedly found
      to increase CIPN in a randomized trial. We investigated the long-term patterns of
      CIPN among patients in this trial. Methods: S0715 was a randomized, double-blind,
      multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24
      weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer.
      CIPN was measured by the 11-item neurotoxicity (NTX) component of the FACT-Taxane
      scale at weeks 12, 24, 36, 52, and 104. We examined NTX scores over two years
      using linear mixed models for longitudinal data. Individual time points were
      examined using linear regression. Regression analyses included stratification
      factors and the baseline score as covariates. All statistical tests were two
      sided. Results: Four-hundred nine subjects were eligible for evaluation. Patients
      receiving ALC had a statistically significantly (P = .01) greater reduction in
      NTX scores (worse CIPN) of -1.39 points (95% confidence interval [CI] = -2.48 to 
      0.30) than the placebo group. These differences were particularly evident at
      weeks 24 (-1.68, 95% CI = -3.02 to -0.33), 36 (-1.37, 95% CI = -2.69 to -0.04),
      and 52 (-1.83, 95% CI = -3.35 to -0.32). At 104 weeks, 39.5% on the ALC arm and
      34.4% on the placebo arm reported a five-point (10%) decrease from baseline. For
      both treatment groups, 104-week NTX scores were statistically significantly
      different compared with baseline (P < .001). Conclusions: For both groups, NTX
      scores were reduced from baseline and remained persistently low. Twenty-four
      weeks of ALC therapy resulted in statistically significantly worse CIPN over two
      years. Understanding the mechanism of this persistent effect may inform
      prevention and treatment strategies. Until then, the potential efficacy and harms
      of commonly used supplements should be rigorously studied.

PMID- 29361043
TI  - Keratin hydrolysis by dermatophytes.
AB  - Dermatophytes are the most common cause of superficial fungal infections (tinea
      infections) and are a specialized group of filamentous fungi capable of infecting
      and degrading keratinised tissues, including skin, hair, and nail. Essential to
      their pathogenicity and virulence is the production of a broad spectrum of
      proteolytic enzymes and other key proteins involved in keratin biodegradation and
      utilization of its breakdown products. The initial stage of biodegradation of
      native keratin is considered to be sulfitolysis, in which the extensive disulfide
      bridges present in keratin are hydrolyzed, although some secreted subtilisins can
      degrade dye-impregnated keratin azure without prior reduction (Sub3 and Sub4).
      Sulfitolysis facilitates the extracellular biodegradation of keratin by the
      dermatophytes' extensive array of endo- and exoproteases. The importance of
      dermatophyte proteases in infection is widely recognized, and these enzymes have
      also been identified as important virulence determinants and allergens. Finally,
      the short peptide and amino acid breakdown products are taken up by the
      dermatophytes, using as yet poorly characterised transporters, and utilized for
      metabolism. In this review, we describe the process of keratin biodegradation by
      dermatophytes, with an especial focus on recent developments in cutting edge
      molecular biology and '-omic' studies that are helping to dissect the complex
      process of keratin breakdown and utilization.

PMID- 29361044
TI  - Commercial hybrids and mutant genotypes reveal complex protective roles for
      inducible terpenoid defenses in maize.
AB  - Plant defense research is facilitated by the use of genome-sequenced inbred
      lines; however, a foundational knowledge of interactions in commercial hybrids
      remains relevant to understanding mechanisms present in crops. Using an array of
      commercial maize hybrids, we quantified the accumulation patterns of defense
      related metabolites and phytohormones in tissues challenged with diverse fungal
      pathogens. Across hybrids, Southern leaf blight (Cochliobolus heterostrophus)
      strongly elicited specific sesqui- and diterpenoid defenses, namely zealexin A4
      (ZA4) and kauralexin diacids, compared with the stalk-rotting agents Fusarium
      graminearum and Colletotrichum graminicola. With respect to biological activity,
      ZA4 and kauralexin diacids demonstrated potent antimicrobial action against F.
      graminearum. Unexpectedly, ZA4 displayed an opposite effect on C. graminicola by
      promoting growth. Overall, a negative correlation was observed between total
      analyzed terpenoids and fungal growth. Statistical analyses highlighted
      kauralexin A3 and abscisic acid as metabolites most associated with fungal
      suppression. As an empirical test, mutants of the ent-copalyl diphosphate
      synthase Anther ear 2 (An2) lacking kauralexin biosynthetic capacity displayed
      increased susceptibility to C. heterostrophus and Fusarium verticillioides. Our
      results highlight a widely occurring defensive function of acidic terpenoids in
      commercial hybrids and the complex nature of elicited pathway products that
      display selective activities on fungal pathogen species.

PMID- 29361045
TI  - Totally thoracoscopic ablation for atrial fibrillation: a systematic safety
      analysis.
AB  - Aims: Thoracoscopic surgical ablation has evolved into a successful strategy for
      symptomatic atrial fibrillation (AF) refractory to other therapy. More widespread
      referral is limited by the lack of information on potential complications. Our
      aim was to systematically evaluate 30-day complications of totally thoracoscopic
      surgical ablation. Methods and results: We retrospectively studied consecutive
      patients undergoing totally thoracoscopic surgical ablation at a referral centre
      in the Netherlands (2007-2016). Patients received pulmonary vein isolation, with
      additional lesion lines as needed, and left atrial appendage exclusion. The
      primary outcomes were freedom from any complications and freedom from
      irreversible complications at 30-days. Secondary outcomes included intra- and
      post-operative complications according to severity. Included were 558 patients
      with median age 62 years (interquartile range 56-68 years), 70% male and 53% with
      a previous failed catheter ablation. The cohort consisted of 43% paroxysmal AF,
      47% persistent AF, and 10% long-standing persistent AF. Freedom from any 30-day
      complication was 88.2%, and from complications with life-long affecting
      consequences 97.5%. The intra-operative complication rate was 2.3% with no
      strokes or death observed. The median hospital length of stay was 4 days. The
      percentage of patients with major and minor complications at 30-days was 3.2% and
      8.1%, respectively, with one patient dying of an ischaemic stroke. The only
      patient groups with excess complications were women aged >=70 years and patients
      with a history of congestive heart failure. Conclusions: Totally thoracoscopic
      ablation is associated with a low complication rate in a referral centre and may
      be a useful alternative to other rhythm control strategies.

PMID- 29361046
TI  - Targeted endothelial gene deletion of triggering receptor expressed on myeloid
      cells-1 protects mice during septic shock.
AB  - Aims: TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an
      immunoreceptor expressed on neutrophils and monocytes/macrophages whose role is
      to amplify the inflammatory response driven by Toll-Like Receptors engagement.
      The pharmacological inhibition of TREM-1 confers protection in several pre
      clinical models of acute inflammation. In this study, we aimed to decipher the
      role of TREM-1 on the endothelium. Methods and results: We first showed by qRT
      PCR, flow cytometry and confocal microscopy that TREM-1 was expressed in human
      pulmonary microvascular endothelial cells as well as in mouse vasculature (aorta,
      mesenteric artery, and pulmonary vessels). TREM-1 expression was upregulated
      following septic insult. We next observed that TREM-1 engagement impaired mouse
      vascular reactivity and promoted vascular inflammation. The pharmacological
      inhibition of TREM-1 (using the synthetic inhibitory peptide LR12) prevented
      these disorders both in vitro and in vivo. We generated endothelium-conditional
      Trem-1 ko mice (EndoTREM-1-/-) and submitted them to a caecal ligation and
      puncture-induced septic shock. As compared with wild-type littermates, targeted
      endothelial Trem-1 deletion conferred protection during septic shock in
      modulating inflammatory cells mobilization and activation, in restoring
      vasoreactivity, and in improving the survival. Conclusion: We reported that TREM
      1 is expressed and inducible in endothelial cells and plays a direct role in
      vascular inflammation and dysfunction. The targeted deletion of endothelial Trem
      1 conferred protection during septic shock in modulating inflammatory cells
      mobilization and activation, restoring vasoreactivity, and improving survival.
      The effect of TREM-1 on vascular tone, while impressive, deserves further
      investigations including the design of endothelium-specific TREM-1 inhibitors.

PMID- 29361047
TI  - Effects of exogenous inosine monophosphate on growth performance, flavor
      compounds, enzyme activity, and gene expression of muscle tissues in chicken.
AB  - The goal of this experiment was to examine effects of diets supplemented with
      exogenous inosine monophosphate (IMP) on the growth performance, flavor
      compounds, enzyme activity and gene expression of chicken. A total of 1,500
      healthy, 1-day-old male 3-yellow chickens were used for a 52-d experimental
      period. Individuals were randomly divided into 5 groups (group I, II, III, IV, V)
      with 6 replicates per group, and fed a basal diet supplemented with 0.0, 0.05,
      0.1, 0.2, and 0.3% IMP, respectively. There was no significant response to the
      increasing dietary IMP level in average daily feed intake (ADFI), average daily
      gain (ADG), and feed:gain ratio (F/G) (P >= 0.05). IMP content of the breast and
      thigh muscle showed an exponential and linear response to the increasing dietary
      IMP level (P < 0.05), the highest IMP content was obtained when the diet with
      0.3% and 0.2% exogenous IMP was fed. There were significant effects of IMP level
      in diet on free amino acids (FAA) (exponential, linear and quadratic effect, P <
      0.05) and delicious amino acids (DAA) (quadratic effect, P < 0.01) content in
      breast muscle. FAA and DAA content in thigh muscle showed an exponential and
      linear response (P < 0.05), and quadratic response (P < 0.01) to the increasing
      dietary IMP level, the highest FAA and DAA content was obtained when the diet
      with 0.2% exogenous IMP was fed. Dietary IMP supplementation had a quadratic
      effect on 5?-NT and the alkaline phosphatase (ALP) enzyme activity in the breast
      muscle (P < 0.05), and the adenosine triphosphate (ATP) enzyme activity in the
      thigh muscles increased exponentially and linearly with increasing IMP level in
      diet (exponential effect, P = 0.061; linear effect, P = 0.059). Cyclohydrolase
      (ATIC) gene expression in thigh muscle had a quadratic response to the increasing
      dietary IMP level (P < 0.05), 0.2% exogenous IMP group had the highest (AMPD1)
      gene expression of the breast muscle and ATIC gene expression of the thigh
      muscle. These results indicate that dietary IMP did not affect the growth
      performance of chicken, the diet with 0.2 to 0.3% exogenous IMP is optimal to
      improve the meat flavor quality in chicken.

PMID- 29361049
TI  - A persistent giant Eustachian valve: functional tricuspid atresia in a newborn.
AB  - Persistent right valve of the systemic venous sinus is a rare anomaly with
      anatomical variations. This anomaly may present as an obstructive structure that
      can inhibit the antegrade flow through the tricuspid valve. We report on a 4-day
      old neonate who presented with pronounced peripheral and central cyanosis.
      Echocardiographic examination showed a giant Eustachian valve moving towards the
      tricuspid valve during late systole and leading to complete obstruction of the
      inflow. Blood flow was redirected through the persistent foramen ovale, producing
      a right-to-left shunt.

PMID- 29361048
TI  - Role of the cytochrome P-450/ epoxyeicosatrienoic acids pathway in the
      pathogenesis of renal dysfunction in cirrhosis.
AB  - Background: Hepatorenal syndrome (HRS) is a life-threatening complication of
      advanced liver cirrhosis that is characterized by hemodynamic alterations in the
      kidney and other vascular beds. Cytochrome P(CYP)-450 enzymes metabolize
      arachidonic acid to epoxyeicosatrienoic acids (EETs) and 20
      hydroxyeicosatetraenoic acids. These eicosanoids regulate blood pressure,
      vascular tone and renal tubular sodium transport under both physiological and
      pathophysiological states. Methods: Experiments were performed to investigate the
      role of the CYP system in the pathogenesis of renal dysfunction during cirrhosis.
      Rats underwent bile duct ligation (BDL) or sham surgery and were studied at 2, 4
      and 5 weeks post-surgery. In additional experiments, post-BDL rats were treated
      with three daily intraperitoneal doses of either the selective epoxygenase
      inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MSPPOH) or a
      vehicle, starting on Day 22 after surgery. Results: BDL led to progressive renal
      dysfunction that was associated with reduced renal cortical perfusion but without
      any overt histologic changes, consistent with HRS. CYP isoform enzyme expression
      was significantly altered in BDL rats. In the kidney, CYP2C23 expression was
      upregulated at both the mRNA and protein levels in BDL rats, while CYP2C11 was
      downregulated. Histologically, the changes in CYP2C23 and CYP2C11 expression were
      localized to the renal tubules. EET production was increased in the kidneys of
      BDL rats as assessed by urinary eicosanoid levels. Finally, treatment with the
      selective epoxygenase inhibitor MSPPOH significantly reduced renal function and
      renal cortical perfusion in BDL rats, suggesting a homeostatic role for
      epoxygenase-derived eicosanoids. Conclusions: The CYP/EET pathway might represent
      a novel therapeutic target for modulating renal dysfunction in advanced
      cirrhosis.

PMID- 29361050
TI  - Improved cytotoxicity of novel TRAIL variants produced as recombinant fusion
      proteins.
AB  - The TNF-Related Apoptosis Inducing Ligand (TRAIL) cytokine triggers apoptosis
      specifically in cancer cells. Susceptibility of a given cell to TRAIL depends on
      the activity of regulatory proteins, one of the most important of which is BID.
      The aim of this study was to increase the cytotoxic potential of TRAIL against
      cancer cells. TRAIL was fused to the BH3 domain of BID. Hence, TRAIL acted not
      only as an anticancer agent, but also as a specific carrier for the BID fragment.
      Two fusion protein variants were obtained by genetic engineering, harboring two
      different linker sequences. The short linker allowed both parts of the fusion
      protein to fold into their native structures. The long linker influenced the
      structure of the fused proteins but nonetheless resulted in their highest
      cytotoxic activity. Optimal buffer formulation was determined for all the
      analyzed TRAIL variants. Fusing the BH3 domain of BID to TRAIL improved the
      cytotoxic potential of TRAIL. Further, these findings may be useful for the
      optimization of other anticancer drugs based on TRAIL, since the appropriate
      formulation would secure their native structures during prolonged storage.

PMID- 29361051
TI  - Non-Small Cell Lung Carcinoma: Clinical Reasoning in the Management of a Patient
      Referred to Physical Therapy for Costochondritis.
AB  - Background and Purpose: Chest pain, a frequent complaint for seeking medical
      care, is often attributed to musculoskeletal pathology. Costochondritis is a
      common disorder presenting as chest pain. Initial physical therapist examination
      emphasizes red flag screening. Reexamination throughout the episode of care is
      critical, particularly when patients are not progressing and/or in the presence
      of complex pain presentations. The purpose of this case report is to describe the
      clinical reasoning process in the management of a patient referred to physical
      therapy with a medical diagnosis of costochondritis. Case Description: A 59-year
      old woman presented with a 5-month history of left-sided chest pain that had
      progressed to include the cervical and shoulder regions. She reported multiple
      psychosocial stressors; a depression screen was positive. She reported a history
      of asthma and smoking and improvement in recent fatigue, coughing, dyspnea, and
      sweating. At the initial visit, shoulder, cervical, and thoracic active and
      passive range of motion and joint mobility testing reproduced her pain. Allodynia
      was present throughout the painful areas in the left upper quarter. Outcomes: The
      patient demonstrated improvement over 30 days (4 visits). On her fifth visit (day
      35), she reported an exacerbation of her chest and upper extremity pain and noted
      increased fatigue, sweating, dyspnea, and loss of appetite. Even though her pain
      was again reproduced with musculoskeletal testing, the physical therapist
      contacted the patient's physician regarding the change in presentation. A
      subsequent chest computed tomography scan revealed a non-small cell lung
      adenocarcinoma. Discussion: Cancer can masquerade as a musculoskeletal condition.
      This case highlights the importance of screening, clinical reasoning, and
      communication throughout the episode of care, particularly in the presence of
      chronic pain and psychosocial stressors.

PMID- 29361053
TI  - Viral suppressors of RNAi employ a rapid screening mode to discriminate viral RNA
      from cellular small RNA.

PMID- 29361052
TI  - Curve Laterality for Lateral Lumbar Interbody Fusion in Adult Scoliosis Surgery:
      The Concave Versus Convex Controversy.
AB  - BACKGROUND: Minimally invasive lateral lumbar interbody fusion (LLIF) is an
      effective adjunct in adult degenerative scoliosis (ADS) surgery. LLIF approaches
      performed from the concavity or convexity have inherent approach-related risks
      and benefits. OBJECTIVE: To analyze LLIF approach-related complications and
      radiographic and clinical outcomes in patients with ADS. METHODS: A multicenter
      retrospective review of a minimally invasive adult spinal deformity database was
      queried with a minimum of 2-yr follow-up. Patients were divided into 2 groups as
      determined by the side of the curve from which the LLIF was performed: concave or
      convex. RESULTS: No differences between groups were noted in demographic, and
      preoperative or postoperative radiographic parameters (all P > .05). There were 8
      total complications in the convex group (34.8%) and 21 complications in the
      concave group (52.5%; P = .17). A subgroup analysis was performed in 49 patients
      in whom L4-5 was in the primary curve and not in the fractional curve. In this
      subset of patients, there were 6 complications in the convex group (31.6%)
      compared to 19 in the concave group (63.3%; P < .05) and both groups experienced
      significant improvements in coronal Cobb angle, Oswestry Disability Index, and
      Visual Analog Scale score with no difference between groups. CONCLUSION: Patients
      undergoing LLIF for ADS had no statistically significant clinical or operative
      complication rates regardless of a concave or convex approach to the curve.
      Clinical outcomes and coronal plane deformity improved regardless of approach
      side. However, in cases wherein L4-5 is in the primary curve, approaching the
      fractional curve at L4-5 from the concavity may be associated with a higher
      complication rate compared to a convex approach.

PMID- 29361054
TI  - Analysis of the human SOX10 mutation Q377X in mice and its implications for
      genotype-phenotype correlation in SOX10-related human disease.
AB  - Human SOX10 mutations lead to various diseases including Waardenburg syndrome,
      Hirschsprung disease, peripheral demyelinating neuropathy, central
      leukodystrophy, Kallmann syndrome and various combinations thereof. It has been
      postulated that PCWH as a combination of Waardenburg and Hirschsprung disease,
      peripheral neuropathy and central leukodystrophy is caused by heterozygous SOX10
      mutations that result in the presence of a dominantly acting mutant SOX10 protein
      in the patient. One such protein with postulated dominant action is SOX10 Q377X.
      In this study, we generated a mouse model, in which the corresponding mutation
      was introduced into the Sox10 locus in such a way that Sox10 Q377X is
      constitutively expressed. Heterozygous mice carrying this mutation exhibited
      pigmentation and enteric nervous system defects similar to mice in which one
      Sox10 allele was deleted. However, despite presence of the mutant protein in
      Schwann cells and oligodendrocytes throughout development and in the adult, we
      found no phenotypic evidence for neurological defects in peripheral or central
      nervous systems. In the nervous system, the mutant Sox10 protein did not act in a
      dominant fashion but rather behaved like a hypomorph with very limited residual
      function. Our results question a strict genotype-phenotype correlation for SOX10
      mutations and argue for the influence of additional factors including genetic
      background.

PMID- 29361055
TI  - Selective terminal methylation of a tRNA wobble base.
AB  - Active tRNAs are extensively post-transcriptionally modified, particularly at the
      wobble position 34 and the position 37 on the 3'-side of the anticodon. The 5
      carboxy-methoxy modification of U34 (cmo5U34) is present in Gram-negative tRNAs
      for six amino acids (Ala, Ser, Pro, Thr, Leu and Val), four of which (Ala, Ser,
      Pro and Thr) have a terminal methyl group to form 5-methoxy-carbonyl-methoxy
      uridine (mcmo5U34) for higher reading-frame accuracy. The molecular basis for the
      selective terminal methylation is not understood. Many cmo5U34-tRNAs are
      essential for growth and cannot be substituted for mutational analysis. We show
      here that, with a novel genetic approach, we have created and isolated mutants of
      Escherichia coli tRNAPro and tRNAVal for analysis of the selective terminal
      methylation. We show that substitution of G35 in the anticodon of tRNAPro
      inactivates the terminal methylation, whereas introduction of G35 to tRNAVal
      confers it, indicating that G35 is a major determinant for the selectivity. We
      also show that, in tRNAPro, the terminal methylation at U34 is dependent on the
      primary m1G methylation at position 37 but not vice versa, indicating a
      hierarchical ranking of modifications between positions 34 and 37. We suggest
      that this hierarchy provides a mechanism to ensure top performance of a tRNA
      inside of cells.

PMID- 29361056
TI  - In vitro isolation of small-molecule-binding aptamers with intrinsic dye
      displacement functionality.
AB  - Aptamer-based sensors offer a powerful tool for molecular detection, but the
      practical implementation of these biosensors is hindered by costly and laborious
      sequence engineering and chemical modification procedures. We report a simple
      strategy for directly isolating signal-reporting aptamers in vitro through
      systematic evolution of ligands by exponential enrichment (SELEX) that transduce
      binding events into a detectable change of absorbance via target-induced
      displacement of a small-molecule dye. We first demonstrate that
      diethylthiatricarbocyanine (Cy7) can stack into DNA three-way junctions (TWJs) in
      a sequence-independent fashion, greatly altering the dye's absorbance spectrum.
      We then design a TWJ-containing structured library and isolate an aptamer against
      3,4-methylenedioxypyrovalerone (MDPV), a synthetic cathinone that is an emerging
      drug of abuse. This aptamer intrinsically binds Cy7 within its TWJ domain, but
      MDPV efficiently displaces the dye, resulting in a change in absorbance within
      seconds. This assay is label-free, and detects nanomolar concentrations of MDPV.
      It also recognizes other synthetic cathinones, offering the potential to detect
      newly-emerging designer drugs, but does not detect structurally-similar non
      cathinone compounds or common cutting agents. Moreover, we demonstrate that the
      Cy7-displacement colorimetric assay is more sensitive than a conventional strand
      displacement fluorescence assay. We believe our strategy offers an effective
      generalized approach for the development of sensitive dye-displacement
      colorimetric assays for other small-molecule targets.

PMID- 29361057
TI  - Adherence to low-sodium Dietary Approaches to Stop Hypertension-style diet may
      decrease the risk of incident chronic kidney disease among high-risk patients: a
      secondary prevention in prospective cohort study.
AB  - Background: Considering the fact that subjects with dysglycemia, dyslipidemia or
      high blood pressure are at high risk for chronic kidney disease (CKD), long-term
      adherence to the Dietary Approaches to Stop Hypertension (DASH)-style diet may
      contribute to the prevention of CKD. This study, examined the association between
      adherence to the low-sodium DASH-style diet and incident CKD among high-risk
      adults over 3 years of follow-up. Methods: In this prospective cohort study
      (followed up for 3 years, 2012-15), we selected 1100 subjects with dysglycemia,
      2715 with dyslipidemia and 2089 with high blood pressure, all of whom were free
      of CKD at baseline (2009-11) in a subgroup of the Tehran Lipid and Glucose Study.
      The low-sodium DASH-style diet was designed based on eight foods and nutrients
      using a food frequency questionnaire. Estimated glomerular filtration rate (eGFR)
      was calculated and CKD was defined as eGFR <60 mL/min/1.73 m2. Results: After 3
      years of follow-up, among subjects with dysglycemia, dyslipidemia or high blood
      pressure, the rate of incident CKD was ~16%. In multivariable-adjusted analyses
      for participants in the highest compared with the lowest quartile of the low
      sodium DASH-style diet score, the odds ratio was 0.58 [95% confidence interval
      (CI) 0.36-0.92] for subjects with dysglycemia, 0.64 (95% CI 0.48-0.87) for
      subjects with dyslipidemia and 0.62 (95% CI 0.44-0.87) for subjects with high
      blood pressure. Conclusions: Higher adherence to the low-sodium DASH-style diet
      might be associated with a lower risk of incident CKD among high-risk adults,
      highlighting the importance of adherence to the low-sodium DASH-style diet in
      substantially reducing both the occurrence of CKD and the burden imposed by it in
      the future.

PMID- 29361058
TI  - Toward a Molecular Understanding of Abscisic Acid Actions in Floral Transition.
AB  - The transition from the vegetative growth phase to flowering is a crucial
      checkpoint for plant reproduction and survival, especially under environmental
      stress conditions. Numerous factors regulate flowering time, including exogenous
      environmental cues such as day length and temperature, as well as salt and
      drought stresses, and endogenous phytohormone signaling cascades. Gibberellins
      and ABA are one classic combination of phytohormones which antagonistically
      regulate several biological processes, including seed dormancy and germination,
      primary root growth and seedling development. As regards control of flowering
      time, gibberellin exhibits a positive role, and represents an important pathway
      in the regulation of floral transition. However, over the past decades, numerous
      investigations have demonstrated that the contribution of the stress hormone ABA
      to floral transition is still controversial, as both positive and negative
      effects have been documented. It is important to determine why and how ABA shows
      this contradictory effect on flowering time. In this up to date review, primarily
      based on recent publications and emerging data, we summarize the distinct and
      contrasting roles of ABA on floral transition, while the detailed molecular
      mechanisms underlying these roles are discussed. Finally, the remaining
      challenges and open questions in this topic are presented.

PMID- 29361059
TI  - TcR-alpha recombinations in renal cell carcinoma exome files correlate with an
      intermediate level of T-cell exhaustion biomarkers.
AB  - Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated
      presence and variability, for both TcR-alpha and -beta, when compared to marginal
      tissue, reflecting an opportunity to assess tumor immunogenicity by comparison
      with marginal tissue T cells. PD-1, PD-L2, CTLA4 and FOXP3, all of which are
      implicated in the evasion of an anti-tumor immune response, had a significantly
      higher expression for samples representing co-detection of productive TcR-alpha
      and -beta recombination reads. Samples representing tumors with productive TcR
      alpha recombination reads but no detectable, productive TcR-beta recombination
      reads, reflected a 20% survival advantage, and RNASeq data indicated an
      intermediate level of immune checkpoint gene expression for those samples. These
      results raise the question of whether relatively high levels of detection of
      productive TcR-alpha recombination reads, in comparison with detection of reads
      representing the TcR-beta gene, identify a microenvironment that has not yet
      entered a T-cell exhaustion phase and may thereby represent conditions for immune
      enhancements that do not require anti-immune checkpoint therapies.

PMID- 29361060
TI  - A Negative Regulator in Response to Salinity in Rice: Oryza sativa Salt-, ABA-
      and Drought-Induced RING Finger Protein 1 (OsSADR1).
AB  - RING (Really Interesting New Gene) finger proteins play crucial roles in abiotic
      stress responses in plants. We report the RING finger E3 ligase gene, an Oryza
      sativa salt, ABA and drought stress-induced RING finger protein 1 gene (OsSADR1).
      We demonstrated that although OsSAR1 possesses E3 ligase activity, a single amino
      acid substitution (OsSADR1C168A) in the RING domain resulted in no E3 ligase
      activity, suggesting that the activity of most E3s is specified by the RING
      domain. Additional assays substantiated that OsSADR1 interacts with three
      substrates-no E3 ligase acti and OsPIRIN, and mediates their proteolysis via the
      26S proteasome pathway. For OsSADR1, approximately 62% of the transient signals
      were in the cytosol and 38% in the nucleus. However, transiently expressed
      OsSADR1 was primarily expressed in the nucleus (70%) in 200 mM salt-treated rice
      protoplasts. The two nucleus-localized proteins (OsSNAC2 and OsGRAS44) interacted
      with OsSADR1 in the cytosol and nucleus. Heterogeneous overexpression of OsSADR1
      in Arabidopsis resulted in sensitive phenotypes for salt- and mannitol-responsive
      seed germination and seedling growth. With ABA, OsSADR1 overexpression in plants
      produced highly tolerant phenotypes, with morphological changes in root length
      and stomatal closure. The ABA-tolerant transgenic plants also showed
      hypersensitivity phenotypes under severe water deficit conditions. Taken
      together, OsSADR1 may act as a regulator in abiotic stress responses by
      modulating target protein levels.

PMID- 29361061
TI  - Overall mortality of Canadian Armed Forces personnel enrolled 1976-2012.
AB  - Background: Military personnel may be exposed to hazardous substances or
      environments, making health surveillance critical. However, surveillance is
      frequently handicapped by long lag times between exposure(s) and outcomes, which
      often manifest post-military release and are often not recorded. Aims: To
      describe the burden of mortality in still serving and released Canadian Armed
      Forces (CAF) personnel. Methods: The Canadian Forces Cancer and Mortality Study
      II (CF CAMS II) is an interdepartmental record linkage study using CAF pay data
      and Statistics Canada cancer and mortality data. The cohort included all Regular
      Force and class C Reservist men and women who first enrolled in the CAF between
      1976 and 2012, inclusive. The anonymized linked data included death data,
      including cause and location of death. All-cause mortality (ACM) and
      International Classification of Disease (ICD)-10 chapter-level mortality (CLM)
      were quantified using standardized mortality ratios (SMRs), with the Canadian
      general population (CGP) as the reference population. Results: Approximately 6870
      deaths occurred during over 5 million person-years of observations. For ACM, the
      CAF risk of death was significantly lower than the CGP for both sexes (females: n
      = 540, SMR = 0.76 [95% CI 0.69-0.82]; males: n = 6330, SMR = 0.79 [95% CI 0.77
      0.81]). In the CLM analysis, SMRs were significantly lower than, or not
      statistically different from, 1.0 for all ICD chapters. Conclusions: Military
      service may have a protective effect that may be partly explained by the healthy
      soldier effect and the stringent selection process at enrolment.

PMID- 29361062
TI  - RGBM: regularized gradient boosting machines for identification of the
      transcriptional regulators of discrete glioma subtypes.
AB  - We propose a generic framework for gene regulatory network (GRN) inference
      approached as a feature selection problem. GRNs obtained using Machine Learning
      techniques are often dense, whereas real GRNs are rather sparse. We use a Tikonov
      regularization inspired optimal L-curve criterion that utilizes the edge weight
      distribution for a given target gene to determine the optimal set of TFs
      associated with it. Our proposed framework allows to incorporate a mechanistic
      active biding network based on cis-regulatory motif analysis. We evaluate our
      regularization framework in conjunction with two non-linear ML techniques, namely
      gradient boosting machines (GBM) and random-forests (GENIE), resulting in a
      regularized feature selection based method specifically called RGBM and RGENIE
      respectively. RGBM has been used to identify the main transcription factors that
      are causally involved as master regulators of the gene expression signature
      activated in the FGFR3-TACC3-positive glioblastoma. Here, we illustrate that RGBM
      identifies the main regulators of the molecular subtypes of brain tumors. Our
      analysis reveals the identity and corresponding biological activities of the
      master regulators characterizing the difference between G-CIMP-high and G-CIMP
      low subtypes and between PA-like and LGm6-GBM, thus providing a clue to the yet
      undetermined nature of the transcriptional events among these subtypes.

PMID- 29361064
TI  - The Fundamentals of Person-Centered Care for Individuals With Dementia.
AB  - Background and Objectives: Person-centered care is a philosophy of care built
      around the needs of the individual and contingent upon knowing the unique
      individual through an interpersonal relationship. This review article outlines
      the history, components, and impact of person-centered care practices. Research
      Design and Methods: Through literature review, published articles on person
      centered measures and outcomes were examined. Results: The history of person
      centered care was described, core principles of care for individuals with
      dementia outlined, current tools to measure person-centered care approaches
      reviewed, and outcomes of interventions discussed. Discussion and Implications:
      Evidence-based practice recommendations for person-centered care for individuals
      with dementia are outlined. More research is needed to further assess the
      outcomes of person-centered care approaches and models.

PMID- 29361063
TI  - Progressive Support for Activities of Daily Living for Persons Living With
      Dementia.
AB  - Background and Objectives: Dementia is accompanied by increasing need for support
      in activities of daily living (ADLs). This brief report/literature review
      summarizes the practices to care for early stage, middle stage, and late stage
      ADL needs (dressing, toileting, and eating/nutrition), and examines commonalities
      across ADL needs and the extent to which practices are reflected in guidelines
      and/or evidence. Research Design and Methods: A review of the grey and peer
      reviewed literature, using some but not all procedures of a systematic review.
      Key terms were identified for ADLs overall and for each of the 3 ADLs, and a
      search was conducted using these words in combination with (a) dementia,
      Alzheimer's disease, and similar terms, and (b) practices, interventions,
      guidelines, recommendations, and similar terms. Searches were conducted using
      databases of peer-reviewed literature as well as the Grey Literature Reports and
      Google search engine. Sources were included if they provided evidence or
      recommendations on interventions to address ADL functioning for dressing,
      toileting, and feeding for persons living with dementia. Results: As cognitive
      and functional impairment increases, the number of care practices and themes that
      embody care practices increases. The majority of practices are evidence-based,
      and most evidence is incorporated into guidelines. Discussion and Implications:
      Virtually all practices reflect person-centered care principles. Five
      recommendations summarize the evidence and recommendations related to providing
      support to persons living with dementia in relation to dressing, toileting, and
      eating/nutrition.

PMID- 29361065
TI  - From Research to Application: Supportive and Therapeutic Environments for People
      Living With Dementia.
AB  - The evidence about the role the designed and built environment plays in
      supporting individuals living with dementia has been steadily mounting for almost
      40 years. Beginning with the work of M. Powell Lawton at the Weiss Pavilion at
      the Philadelphia Geriatric Center, there are now dozens of researchers who are
      exploring how the environment can be either supportive and therapeutic, indeed
      even serving as a prosthetic for various changes in cognition, or be a barrier to
      independent functioning and high quality of life. Two recent literature reviews
      published on the impact of environmental factors and characteristics on
      individuals living with dementia clearly delineate evidence that the environment
      can have a therapeutic or a debilitating impact on individuals living with
      dementia. Rather than duplicate these excellent reviews, this article puts the
      knowledge gleaned from this research into the shifting context that is long-term
      care. This article begins with an exploration of the evolution of approaches to
      the design of spaces for individuals living with dementia from traditional or
      medical models, to special care units (SCUs), to person-centered care (PCC),
      which is the organizing theme of this supplemental issue. A novel, person
      centered way of conceptualizing the domains of environmental systems is then
      presented and used as the framework for structuring recommendations and creating
      supportive and therapeutic environments for individuals living with dementia.
      Although there are distinct pathophysiological and behavioral manifestations of
      different forms of dementia, there is almost no evidence that suggests
      alternative environmental characteristics are better for one type of dementia
      over another. Thus, this article will refer to "individuals living with dementia"
      as opposed to Alzheimer's disease or other specific forms of dementia. Further,
      this article only addresses residential environments: homes in the community,
      independent and assisted living residences and nursing homes. It does not address
      other settings, such as hospitals or hospice, or work and public community
      spaces, such as stores. It is recognized that individuals living with dementia do
      spend time in all these spaces, and fortunately, there is growing interest in
      creating more dementia-friendly communities, but they will not be addressed in
      this article. Most of the research that has been done has focused on shared
      residential settings, so that will be the primary focus on this article.

PMID- 29361067
TI  - Evidence-Based Interventions for Transitions in Care for Individuals Living With
      Dementia.
AB  - Background and Objectives: Despite numerous, often predictable, transitions in
      care, little is known about the core elements of successful transitions in care
      specifically for persons with dementia. The paper examines available evidence
      based interventions to improve the care transitions for persons with dementia and
      their caregivers. Research Design and Methods: A state-of-the-art review was
      conducted for research published on interventions targeting transitions in care
      for persons living with dementia and their caregivers through January 2017.
      Results: Our review revealed seven evidence-based interventions to
      postpone/prevent or reduce care transitions specific to persons living with
      dementia. Effective approaches appear to be those that involve the individual and
      caregiver in establishing goals of care, educate the individual and caregiver
      about likely transitions in care; provide timely communication of information
      about the individual, create strong inter professional teams with competencies in
      dementia care, and implement evidence-based models of practice. Discussion and
      Implications: Five essential features for consistent and supported care
      transitions for persons with dementia and their caregivers are recommended.
      Findings reinforce the need for additional research and adaptation of evidence
      based transitions in care interventions.

PMID- 29361066
TI  - Ongoing Medical Management to Maximize Health and Well-being for Persons Living
      With Dementia.
AB  - Background and Objectives: Persons living with dementia have complex care needs
      including memory loss that should be taken into account by providers and family
      caregivers involved with their care. The prevalence of comorbid conditions in
      people with dementia is high and, thus, how primary care, community providers and
      family caregivers provide best practice care, person-centered care is important.
      Research Design and Methods: Care providers should understand the ongoing medical
      management needs of persons living with dementia in order to maximize their
      quality of life, proactively plan for their anticipated needs, and be as well
      prepared as possible for health crises that may occur. Results: This article
      provides eight practice recommendations intended to promote understanding and
      support of the role of nonphysician care providers in educating family caregivers
      about ongoing medical management to improve the wellbeing of persons living with
      dementia. Discussion and Implications: Key among these are recommendations to use
      nonpharmacological interventions to manage behavioral and psychological symptoms
      of dementia as the first line of treatment and recommendations on how to best
      support the use and discontinuation of pharmacological interventions as
      necessary.

PMID- 29361068
TI  - Meeting the Informational, Educational, and Psychosocial Support Needs of Persons
      Living With Dementia and Their Family Caregivers.
AB  - Background and Objectives: Meeting the unique and changing needs of individuals
      living with Alzheimer's disease and their family caregivers can be very
      challenging given the dynamic and often unpredictable nature of the disease.
      Effective programs are available to help families manage the challenges they will
      face. Research Design and Methods: This article first describes the educational,
      information, and support needs of individuals living dementia and their family
      caregivers across all stages of Alzheimer's. Next, we describe the variety of
      services and program models targeted to the needs of individuals living with
      Alzheimer's disease or other types of dementia and their families. Results: These
      programs can help ensure that person- and family-centered care is maintained from
      time of first symptoms through end-of-life. Discussion and Implications: We end
      with our recommendations for maintaining person- and family-centered care through
      the provision of targeted information, education, and support to individuals and
      their families.

PMID- 29361070
TI  - Nonphysician Care Providers Can Help to Increase Detection of Cognitive
      Impairment and Encourage Diagnostic Evaluation for Dementia in Community and
      Residential Care Settings.
AB  - In the United States, at least half of older adults living with dementia do not
      have a diagnosis. Their cognitive impairment may not have been detected, and some
      older adults whose physician recommends that they obtain a diagnostic evaluation
      do not follow through on the recommendation. Initiatives to increase detection of
      cognitive impairment and diagnosis of dementia have focused primarily on
      physician practices and public information programs to raise awareness about the
      importance of detection and diagnosis. Nonphysician care providers who work with
      older adults in community and residential care settings, such as aging network
      agencies, public health agencies, senior housing, assisted living, and nursing
      homes, interact frequently with older adults who have cognitive impairment but
      have not had a diagnostic evaluation. These care providers may be aware of signs
      of cognitive impairment and older adults' concerns about their cognition that
      have not been expressed to their physician. Within their scope of practice and
      training, nonphysician care providers can help to increase detection of cognitive
      impairment and encourage older adults with cognitive impairment to obtain a
      diagnostic evaluation to determine the cause of the condition. This article
      provides seven practice recommendations intended to increase involvement of
      nonphysician care providers in detecting cognitive impairment and encouraging
      older adults to obtain a diagnostic evaluation. The Kickstart-Assess-Evaluate
      Refer (KAER) framework for physician practice in detection and diagnosis of
      dementia is used to identify ways to coordinate physician and nonphysician
      efforts and thereby increase the proportion of older adults living with dementia
      who have a diagnosis.

PMID- 29361071
TI  - Person-Centered Assessment and Care Planning.
AB  - The quality of dementia care rendered to individuals and families is contingent
      upon the quality of assessment and care planning, and the degree to which those
      processes are person-centered. This paper provides recommendations for assessment
      and care planning derived from a review of the research literature. These
      guidelines build upon previous recommendations published by the Alzheimer's
      Association, and apply to all settings, types, and stages of dementia. The target
      audience for these guidelines includes professionals, paraprofessionals, and
      direct care workers, depending on their scope of practice and training.

PMID- 29361069
TI  - Evidence-Based Nonpharmacological Practices to Address Behavioral and
      Psychological Symptoms of Dementia.
AB  - Background and Objectives: To draw from systematic and other literature reviews
      to identify, describe, and critique nonpharmacological practices to address
      behavioral and psychological symptoms of dementia (BPSDs) and provide evidence
      based recommendations for dementia care especially useful for potential adopters.
      Research Design and Methods: A search of systematic and other literature reviews
      published from January 2010 through January 2017. Nonpharmacological practices
      were summarized to describe the overall conceptual basis related to
      effectiveness, the practice itself, and the size and main conclusions of the
      evidence base. Each practice was also critically reviewed to determine
      acceptability, harmful effects, elements of effectiveness, and level of
      investment required, based on time needed for training/implementation,
      specialized care provider requirements, and equipment/capital requirements.
      Results: Nonpharmacological practices to address BPSDs include sensory practices
      (aromatherapy, massage, multi-sensory stimulation, bright light therapy),
      psychosocial practices (validation therapy, reminiscence therapy, music therapy,
      pet therapy, meaningful activities), and structured care protocols (bathing,
      mouth care). Most practices are acceptable, have no harmful effects, and require
      minimal to moderate investment. Discussion and Implications: Nonpharmacological
      practices are person-centered, and their selection can be informed by considering
      the cause and meaning of the individual's behavioral and psychological symptoms.
      Family caregivers and paid care providers can implement evidence-based practices
      in home or residential care settings, although some practices require the
      development of more specific protocols if they are to become widely used in an
      efficacious manner.

PMID- 29361072
TI  - Long-Term Care Workforce Issues: Practice Principles for Quality Dementia Care.
AB  - Purpose: This article is one in a series of articles in this supplement
      addressing best practice for quality dementia care. The Alzheimer's Association,
      in revising their Dementia Care Practice Recommendations for 2017 has identified
      staff across the long-term care spectrum as a distinct and important determinant
      of quality dementia care. The purpose of this article is to highlight areas for
      developing and supporting a dementia-capable workforce. Methods: The Alzheimer's
      Association Principles For Advocacy To Assure Quality Dementia Care Across
      Settings provide a framework to examine interventions to support the dementia
      care workforce in long-term care settings. Evidence-based approaches that
      represent these principles are discussed: (a) staffing, (b) staff training, (c)
      compensation, (d) supportive work environments, (e) career growth and retention,
      and (f) engagement with family. Results: Although not all settings currently
      require attention to the principles described, this article proposes these
      principles as best practice recommendations. Recommendations and future research
      considerations to further improve the lives of those who live and work in nursing
      homes, assisted living, hospice, and home care, are proposed. Additional areas to
      improve the quality of a dementia care workforce person-centered care
      information, communication and interdepartmental teamwork, and ongoing evaluation
      are discussed.

PMID- 29361073
TI  - Improving Care Through Public Policy.

PMID- 29361074
TI  - Alzheimer's Association Dementia Care Practice Recommendations.

PMID- 29361075
TI  - Function, Shoulder Motion, Pain, and Lymphedema in Breast Cancer With and Without
      Axillary Web Syndrome: An 18-Month Follow-Up.
AB  - Background: Axillary web syndrome (AWS) can develop following breast cancer
      surgery and presents as a tight band of tissue in the axilla with shoulder
      abduction. Objective: The objectives were to determine the prevalence and natural
      history of AWS and the association between AWS and function, range of motion,
      pain, lymphedema, and body mass index (BMI). Design: This study was a
      longitudinal prospective cohort study utilizing a repeated measures design.
      Methods: Axillary web syndrome, function, shoulder range of motion, pain, and
      lymphedema (using circumference, bioimpedance spectroscopy, tissue dielectric
      constant) were assessed in women at 2, 4, and 12 weeks and 18 months following
      breast cancer surgery. Prevalence of AWS and the association with the measured
      outcomes were analyzed. Results: Thirty-six women agreed to participate in the
      study. The cumulative prevalence of AWS was 50% (18/36) at 18 months following
      breast cancer surgery. AWS was identified as a risk factor for reduced function.
      Women with AWS had statistically reduced range of motion, lower BMI, and higher
      number of lymph nodes removed compared to the non-AWS group. Forty-one percent
      (13/32) of women had AWS at 18 months. AWS reoccurred in 6 women following
      resolution, and a new case developed beyond the early postoperative period. The
      overall prevalence of physical impairments ranged from 66% to 97% within the
      first 18 months following surgery regardless of AWS. Limitations: Limitations
      include a small sample size and potential treatment effect. Conclusion: AWS
      occurs in approximately 50% of women following breast cancer surgery. It can
      persist for 18 months and potentially longer, develop beyond the early
      postoperative time period, and reoccur after resolution. Clinicians need to be
      aware of the chronicity of AWS and its association with reduced range of motion
      and function.

PMID- 29361076
TI  - Step-grandparenthood in the United States.
AB  - Objectives: This study provides new information about the demography of step
      grandparenthood in the United States. Specifically, we examine the prevalence of
      step-grandparenthood across birth cohorts and for socioeconomic and racial/ethnic
      groups. We also examine lifetime exposure to the step-grandparent role. Methods:
      Using data from the Panel Study of Income Dynamics and the Health and Retirement
      Study, we use percentages to provide first estimates of step-grandparenthood and
      to describe demographic and socioeconomic variation in who is a step-grandparent.
      We use life tables to estimate the exposure to step-grandparenthood. Results: The
      share of step-grandparents is increasing across birth cohorts. However,
      individuals without a college education and non-Whites are more likely to become
      step-grandparents. Exposure to the step-grandparent role accounts for
      approximately 15% of total grandparent years at age 65 for women and men.
      Discussion: A growing body of research finds that grandparents are increasingly
      instrumental in the lives of younger generations. However, the majority of this
      work assumes that these ties are biological, with little attention paid to the
      role of family complexity across three generations. Understanding the
      demographics of step-grandparenthood sheds light on the family experiences of an
      overlooked, but growing segment of the older adult population in the United
      States.

PMID- 29361077
TI  - SemEHR: A general-purpose semantic search system to surface semantic data from
      clinical notes for tailored care, trial recruitment, and clinical research.
AB  - Objective: Unlocking the data contained within both structured and unstructured
      components of electronic health records (EHRs) has the potential to provide a
      step change in data available for secondary research use, generation of
      actionable medical insights, hospital management, and trial recruitment. To
      achieve this, we implemented SemEHR, an open source semantic search and analytics
      tool for EHRs. Methods: SemEHR implements a generic information extraction (IE)
      and retrieval infrastructure by identifying contextualized mentions of a wide
      range of biomedical concepts within EHRs. Natural language processing annotations
      are further assembled at the patient level and extended with EHR-specific
      knowledge to generate a timeline for each patient. The semantic data are serviced
      via ontology-based search and analytics interfaces. Results: SemEHR has been
      deployed at a number of UK hospitals, including the Clinical Record Interactive
      Search, an anonymized replica of the EHR of the UK South London and Maudsley
      National Health Service Foundation Trust, one of Europe's largest providers of
      mental health services. In 2 Clinical Record Interactive Search-based studies,
      SemEHR achieved 93% (hepatitis C) and 99% (HIV) F-measure results in identifying
      true positive patients. At King's College Hospital in London, as part of the
      CogStack program (github.com/cogstack), SemEHR is being used to recruit patients
      into the UK Department of Health 100 000 Genomes Project (genomicsengland.co.uk).
      The validation study suggests that the tool can validate previously recruited
      cases and is very fast at searching phenotypes; time for recruitment criteria
      checking was reduced from days to minutes. Validated on open intensive care EHR
      data, Medical Information Mart for Intensive Care III, the vital signs extracted
      by SemEHR can achieve around 97% accuracy. Conclusion: Results from the multiple
      case studies demonstrate SemEHR's efficiency: weeks or months of work can be done
      within hours or minutes in some cases. SemEHR provides a more comprehensive view
      of patients, bringing in more and unexpected insight compared to study-oriented
      bespoke IE systems. SemEHR is open source, available at
      https://github.com/CogStack/SemEHR.

PMID- 29361078
TI  - Outcome of autosomal dominant polycystic kidney disease patients on peritoneal
      dialysis: a national retrospective study based on two French registries (the
      French Language Peritoneal Dialysis Registry and the French Renal Epidemiology
      and Information Network).
AB  - Background: Pathological features of autosomal dominant polycystic kidney disease
      (ADPKD) include enlarged kidney volume, higher frequency of digestive
      diverticulitis and abdominal wall hernias. Therefore, many nephrologists have
      concerns about the use of peritoneal dialysis (PD) in ADPKD patients. We aimed to
      analyse survival and technique failure in ADPKD patients treated with PD.
      Methods: We conducted two retrospective studies on patients starting dialysis
      between 2000 and 2010. We used two French registries: the French Renal
      Epidemiology and Information Network (REIN) and the French language Peritoneal
      Dialysis Registry (RDPLF). Using the REIN registry, we compared the clinical
      features and outcomes of ADPKD patients on PD (n = 638) with those of ADPKD
      patients on haemodialysis (HD) (n = 4653); with the RDPLF registry, those same
      parameters were determined for ADPKD patients on PD (n = 797) and compared with
      those of non-ADPKD patients on PD (n = 12 059). Results: A total of 5291 ADPKD
      patients and 12 059 non-ADPKD patients were included. Analysis of the REIN
      registry found that ADPKD patients treated with PD represented 10.91% of the
      ADPKD population. During the study period, PD was used for 11.2% of the non-ADPKD
      population. Compared with ADPKD patients on HD, ADPKD patients on PD had higher
      serum albumin levels (38.8 +/- 5.3 versus 36.8 +/- 5.7 g/dL, P < 0.0001) and were
      less frequently diabetic (5.31 versus 7.71%, P < 0.03). The use of PD in ADPKD
      patients was positively associated with the occurrence of a kidney
      transplantation but not with death [hazard ratio 1.15 (95% confidence interval
      0.84-1.58)]. Analysis of the RDPLF registry found that compared with non-ADPKD
      patients on PD, ADPKD patients on PD were younger and had fewer comorbidities and
      better survival. ADPKD status was not associated with an increased risk of
      technique failure or an increased risk of peritonitis. Conclusions: According to
      our results, PD is proposed to a selected population of ADPKD patients, PD does
      not have a negative impact on ADPKD patients' overall survival and PD technique
      failure is not influenced by ADPKD status. Therefore PD is a reasonable option
      for ADPKD patients.

PMID- 29361079
TI  - Hand Edema in Patients at Risk of Breast Cancer-Related Lymphedema: Health
      Professionals Should Take Notice.
AB  - Background: There is little research on hand edema in the population at risk for
      breast cancer-related lymphedema (BCRL). Objectives: Study aims included
      reporting potential importance of hand edema (HE) as a risk factor for
      progression of edema in patients treated for breast cancer at risk for BCRL,
      reporting risk factors for BCRL, and reporting treatment of HE. Design/Methods:
      This was a retrospective analysis of 9 patients treated for breast cancer in
      Massachusetts General Hospital's lymphedema screening program who presented with
      isolated HE. Limb volumes via perometry, BCRL risk factors, and HE treatment are
      reported. Results: Edema was mostly isolated to the hand. Three patients had arm
      edema >5% on perometry; and 2 of these had edema outside the hand on clinical
      examination. Patients were at high risk of BCRL with an average of 2.9/5 known
      risk factors. Arm edema progressed to >10% in 2 high-risk patients. Treatment
      resulted in an average hand volume reduction of 10.2% via perometry and
      improvement upon clinical examination. Limitations: The small sample size and
      lack of validated measures of subjective data were limitations. Conclusions: In
      this cohort, patients with HE carried significant risk factors for BCRL. Two out
      of 9 (22%), both carrying >=4/5 risk factors, progressed to edema >10%. Isolated
      HE may be a prognostic factor for edema progression in patients treated for
      breast cancer at risk for BCRL. Further research is warranted.

PMID- 29361081
TI  - Redundant roles of Bradyrhizobium oligotrophicum Cu-type (NirK) and cd1-type
      (NirS) nitrite reductase genes under denitrifying conditions.
AB  - Reduction of nitrite to nitric oxide gas by respiratory nitrite reductases (NiRs)
      is the key step of denitrification. Denitrifiers are strictly divided into two
      functional groups based on whether they possess the copper-containing nitrite
      reductase (CuNiR) encoded by nirK or the cytochrome cd1 nitrite reductase (cdNiR)
      encoded by nirS. Recently, some organisms carrying both nirK and nirS genes have
      been found. Bradyrhizobium oligotrophicum S58 is a nitrogen-fixing oligotrophic
      bacterium that carries a set of genes for complete denitrification of nitrate to
      dinitrogen, including nirK and nirS genes. We show that denitrification in S58 is
      functional under low-oxygen conditions (anaerobiosis and microaerobiosis), but
      not under aerobiosis. Under denitrifying conditions, the DeltanirK and DeltanirS
      single S58 mutants grew normally and their NiR activity was not affected.
      However, the DeltanirKS double mutant grew more slowly, presumably because the
      impaired NiR activity resulted in nitrite accumulation in the medium. These
      results suggest a redundant role for nirK and nirS genes in B. oligotrophicum S58
      denitrification. In addition, we found that the nirS gene product, but not that
      of nirK, maintains swimming motility of S58 under aerobic and low-oxygen
      conditions in the presence of nitrate.

PMID- 29361082
TI  - Dietary Protein and Carbohydrate Levels Affect Performance and Digestive
      Physiology of Plodia interpunctella (Lepidoptera: Pyralidae).
AB  - In this study, life history and nutritional indices of Plodia interpunctella
      (Hubner) (Lepidoptera: Pyralidae) was evaluated on six food commodities: dried
      fig, dried wheat germ, dried white mulberry, groundnut, pistachio, and raisin,
      compared with artificial diet. The influence of dietary macronutrient content on
      digestive alpha-amylase was also assessed. A delay in the developmental time of
      P. interpunctella immature stages was detected when larvae were fed on raisin.
      The highest survival rate of immature stages was on the artificial diet, and the
      lowest was on raisin. The highest realized fecundity and fertility were recorded
      for the females reared on artificial diet. Overall, fourth instar P.
      interpunctella reared on artificial diet had the highest relative consumed and
      growth rate, and lowest rates were observed in larvae fed raisin. Amylolytic
      activity and isoform patterns varied depending on larval instar and diets, but
      were higher for larvae fed artificial diet with moderate carbohydrate and
      protein. Zymograms showed the presence of three isoforms of alpha-amylase in
      midgut extracts of P. interpunctella fed different diets. Larvae fed dried white
      mulberry, fig, and raisin had one (A2) alpha-amylase isoform. The data suggest
      that dietary carbohydrate and protein content induce changes in nutritional
      efficiency, development, and alpha-amylase activity. A survey of the differences
      in digestive enzyme activity in response to macronutrient balance and imbalance
      highlight their importance in the nutrition of insects.

PMID- 29361080
TI  - Deletion size analysis of 1680 22q11.2DS subjects identifies a new recombination
      hotspot on chromosome 22q11.2.
AB  - Recurrent, de novo, meiotic non-allelic homologous recombination events between
      low copy repeats, termed LCR22s, leads to the 22q11.2 deletion syndrome
      (22q11.2DS; velo-cardio-facial syndrome/DiGeorge syndrome). Although most
      22q11.2DS patients have a similar sized 3 million base pair (Mb), LCR22A-D
      deletion, some have nested LCR22A-B or LCR22A-C deletions. Our goal is to
      identify additional recurrent 22q11.2 deletions associated with 22q11.2DS,
      serving as recombination hotspots for meiotic chromosomal rearrangements. Here,
      using data from Affymetrix 6.0 microarrays on 1680 22q11.2DS subjects, we
      identified what appeared to be a nested proximal 22q11.2 deletion in 38 (2.3%) of
      them. Using molecular and haplotype analyses from 14 subjects and their parent(s)
      with available DNA, we found essentially three types of scenarios to explain this
      observation. In eight subjects, the proximal breakpoints occurred in a small
      sized 12 kb LCR distal to LCR22A, referred to LCR22A+, resulting in LCR22A+-B or
      LCR22A+-D deletions. Six of these eight subjects had a nested 22q11.2 deletion
      that occurred during meiosis in a parent carrying a benign 0.2 Mb duplication of
      the LCR22A-LCR22A+ region with a breakpoint in LCR22A+. Another six had a typical
      de novo LCR22A-D deletion on one allele and inherited the LCR22A-A+ duplication
      from the other parent thus appearing on microarrays to have a nested deletion.
      LCR22A+ maps to an evolutionary breakpoint between mice and humans and appears to
      serve as a local hotspot for chromosome rearrangements on 22q11.2.

PMID- 29361083
TI  - Antibody Response to Hepatitis B Virus Vaccine is Impaired in Patients With
      Inflammatory Bowel Disease on Infliximab Therapy.
AB  - Background: Studies have demonstrated an association between anti
      TNF/immunomodulator agents used in inflammatory bowel disease (IBD) and impaired
      hepatitis B virus (HBV) vaccine immunogenicity, but little data exist on whether
      specific medication types affect protective HBsAb titers. Our aim was to analyze
      this association. Methods: This is a retrospective cohort study. Inclusion
      criteria: age >=18, diagnosis of Crohn's disease (CD) or ulcerative colitis (UC),
      previous HBV vaccination series and/or >=1 positive HBsAb, and record of IBD
      therapy in 6 months before titer level. Patients were stratified based upon
      medication exposures: anti-TNF, immunomodulator, combination anti-TNF and
      immunomodulatory, and a reference arm. Titer levels following vaccination and
      specific medication types given in the 6 months before titer were recorded.
      Seroprotection was defined as HBsAb >=10 IU/l and >=100 IU/l. Results: The study
      cohort (N = 391) was 70.8% white, 51.4% female and 64.2% had CD and 35.8% had UC.
      The mean age was 45.8 years. A significantly lower percentage of patients exposed
      to anti-TNF, immunomodulator or dual therapy had titers >=10 (P < 0.01).
      Regarding specific medications, only patients exposed to infliximab (P < 0.01)
      were less likely to have titer levels >=10, after controlling for other
      medication exposures, age at titer level, and interval time between
      vaccination/titer level. This was not found for patients exposed to adalimumab,
      methotrexate, 6-mercaptopurine, or azathioprine. Conclusions: Patients exposed to
      infliximab were significantly less likely to have protective HBsAb titer levels
      following vaccination, a trend not seen in patients on adalimumab. Efforts to
      vaccinate IBD patients against HBV before use of immunomodulators and anti-TNFs,
      infliximab specifically, and screen periodically thereafter must be reinforced.

PMID- 29361084
TI  - Lactobacillus brevis KB290 With Vitamin A Ameliorates Murine Intestinal
      Inflammation Associated With the Increase of CD11c+ Macrophage/CD103- Dendritic
      Cell Ratio.
AB  - Background: The ratio of colonic anti-inflammatory CD11c+ macrophages (MPs) to
      inflammatory CD103- dendritic cells (DCs) plays pivotal roles in intestinal
      inflammation. Little is known about how the ratio is regulated by lactic acid
      bacteria (LAB) and bifidobacteria (Bif). We investigated the contribution of
      LAB/Bif to this ratio. Methods: We established an in vitro experimental system
      using human myeloblastic KG-1 cells, which differentiate into CD11c+ MP-like
      (CD11c+ MPL) and CD103- DC-like (CD103- DCL) cells, and explored effective
      LAB/Bif strains. The selected strain's effect on the colonic CD11c+ MP/CD103- DC
      ratio and intestinal inflammation was examined in mice, and the strain's
      underlying mechanisms were investigated in vitro. Results: We screened 19 strains
      of LAB/Bif, and found that Lactobacillus brevis KB290 (KB290) increased the
      CD11c+ MPL/CD103- DCL cell ratio only in the presence of a vitamin A (VA)
      metabolite, retinoic acid (RA). Supplementation of KB290 with VA increased the
      CD11c+ MP/CD103- DC ratio in healthy mouse and prevented the disruption of the
      ratio during colitis. Supplementation of KB290 with pro-VA (beta-carotene) also
      increased the ratio in healthy mouse and ameliorated the development of colitis.
      The ratio was increased by reduction of CD103- DCs (or CD103- DCL cells). Our in
      vitro data suggested that KB290 induced cell death in CD103- DCL cells in the
      presence of RA signaling. Conclusions: Supplementation of KB290 with VA increases
      the colonic CD11c+ MP/CD103- DC ratio associated with the amelioration of murine
      colitis, suggesting a possible way to control intestinal inflammation by LAB.

PMID- 29361086
TI  - Inhibition of Fibroblast Activation Protein Restores a Balanced Extracellular
      Matrix and Reduces Fibrosis in Crohn's Disease Strictures Ex Vivo.
AB  - Background: Crohn's disease (CD) is a chronic bowel inflammation that ultimately
      leads to fibrosis, for which medical therapy is currently unavailable. Fibrotic
      strictures in CD are characterized by excessive extracellular matrix (ECM)
      deposition, altered balance between matrix metalloproteinases (MMPs) and their
      tissue inhibitors (TIMPs), and overexpression of fibroblast activation protein
      (FAP), a marker of active fibroblasts. Here we investigated the role of FAP
      targeted therapy in ECM remodeling in CD strictures ex vivo. Methods: Bowel
      specimens were obtained from stenotic and nonstenotic ileal segments from 30
      patients with fibrostenotic CD undergoing surgery. FAP expression was evaluated
      in isolated mucosal myofibroblasts by immunoblotting and flow cytometry. Bowel
      tissue cultures were treated with anti-FAP antibody, and soluble collagen, TIMP
      1, and MMPs were measured in tissue culture supernatants by immunoblotting. Anti
      FAP-treated myofibroblasts were analyzed for TIMP-1 expression by immunoblotting,
      for migratory potential by wound healing assay, and for apoptosis by Annexin V
      staining. Results: Myofibroblasts from stenotic CD mucosa showed upregulation of
      FAP expression when compared with nonstenotic mucosa. Treatment of stenotic
      tissues with anti-FAP antibody induced a dose-dependent decrease in collagen
      production, particularly affecting type I collagen. The treatment also reduced
      TIMP-1 production in CD strictures, without altering MMP-3 and MMP-12 secretion.
      Accordingly, anti-FAP treatment inhibited TIMP-1 expression in stenotic CD
      myofibroblasts and enhanced myofibroblast migration without affecting survival.
      Conclusions: FAP inhibition reduced type I collagen and TIMP-1 production by CD
      strictures ex vivo without compromising uninvolved bowel areas. These results
      suggest that targeting FAP could reconstitute ECM homeostasis in fibrostenotic
      CD.

PMID- 29361085
TI  - The Influence of Hormonal Fluctuation on Inflammatory Bowel Disease Symptom
      Severity-A Cross-Sectional Cohort Study.
AB  - Background: Many women with inflammatory bowel disease (IBD) report changes in
      symptoms in association with hormonal changes during menses, pregnancy, and
      hormonal contraceptive use, suggesting a hormonal influence on disease activity.
      We aimed to identify and characterize IBD symptom fluctuations in women during
      times of hormonal variation. Methods: From June 2012 through September 2012,
      women enrolled in Crohn's and Colitis Foundation of America Partners , an online
      Internet cohort of patients with IBD, were invited to participate in this study.
      Using a 5-point Likert scale, participants were asked to rate symptom changes
      during their menstrual cycle, pregnancy, the postpartum period, and after
      menopause. Clinical and demographic differences were assessed using univariate
      and multivariable methods. Results: A total of 1,203 female patients with Crohn's
      disease (CD) and ulcerative colitis (UC) participated (64% CD, 34% UC). Over half
      of the women with IBD reported worsening symptoms during menses. Symptom changes
      were similar between women with CD vs UC, except in pregnancy, where symptom
      worsening during pregnancy was more commonly seen in UC than CD (P = 0.02).
      Overall, women reporting symptom worsening were younger at the time of IBD
      diagnosis (P < 0.01), had lower quality of life (SIBDQ) scores (P < 0.01), and
      had a higher BMI (25 vs 24) than women without symptom worsening. Conclusions:
      Women with IBD report changes in symptom severity during times of hormone
      fluctuation. Further clarification of the role of hormones in IBD is warranted in
      order to understand these relationships and to identify potential management
      strategies for women with IBD and hormonally sensitive gastrointestinal symptoms.

PMID- 29361087
TI  - The Addition of an Immunosuppressant After Loss of Response to Anti-TNFalpha
      Monotherapy in Inflammatory Bowel Disease: A 2-Year Study.
AB  - Background: The addition of an immunosuppressant (IM) after loss of response to
      anti-TNFalpha monotherapy is an emerging strategy of therapeutic optimization in
      patients with inflammatory bowel disease (IBD). However, few clinical data have
      been reported to date. We aimed to evaluate the efficacy and safety of this
      selective combination therapy in patients with IBD. Methods: All consecutive
      patients with loss of response to anti-TNFalpha monotherapy despite an intensive
      dose optimization who added an IM from October 2014 to October 2016 were entered
      into a prospective database. Results: Among 630 patients treated with anti
      TNFalpha agents during the study period, 46 (7.3%) added an IM. A total of 31
      patients (67.4%) were treated with an intravenous anti-TNFalpha (infliximab, as
      originator or biosimilar), while 15 (32.6%) were treated with a subcutaneous anti
      TNFalpha agent (10 adalimumab and 5 golimumab). The mean duration of follow-up
      was 12.8 +/- 7.3 months. Twenty-one patients (45.7%) remained on combination
      therapy at the end of follow-up: 15 (32.6%) maintained a steroid-free remission,
      and 6 (13.0%) achieved a clinical response. In patients who experienced treatment
      success, the median value of C-reactive protein decreased from baseline to the
      end of follow-up (13.2 vs 3.0, P = 0.01; normal values <5 mg/L). Adverse events
      leading to treatment discontinuation were reported in 8 out of 46 patients
      (17.4%). Conclusions: In the largest cohort on this argument reported to date,
      the addition of an IM was an effective and safe optimization strategy after loss
      of response to anti-TNFalpha monotherapy. Low doses of IM were sufficient to
      achieve a clinical response.

PMID- 29361089
TI  - Differential Susceptibility to T Cell-Induced Colitis in Mice: Role of the
      Intestinal Microbiota.
AB  - One of the best characterized mouse models of the inflammatory bowel diseases
      (IBD; Crohn's disease, ulcerative colitis) is the CD4+CD45RBhigh T cell transfer
      model of chronic colitis. Following our relocation to Texas Tech University
      Health Sciences Center (TTUHSC), we observed a dramatic reduction in the
      incidence of moderate-to-severe colitis from a 16-year historical average of 90%
      at Louisiana State University Health Sciences Center (LSUHSC) to <30% at TTUHSC.
      We hypothesized that differences in the commensal microbiota at the 2
      institutions may account for the differences in susceptibility to T cell-induced
      colitis. Using bioinformatic analyses of 16S rRNA amplicon sequence data, we
      quantified and compared the major microbial populations in feces from healthy and
      colitic mice housed at the 2 institutions. We found that the bacterial
      composition differed greatly between mice housed at LSUHSC vs TTUHSC. We
      identified several genera strongly associated with, and signficantly
      overrepresented in high responding RAG-/- mice housed at LSUHSC. In addition, we
      found that colonization of healthy TTUHSC RAG-/- mice with feces obtained from
      healthy or colitic RAG-/- mice housed at LSUHSC transferred susceptibility to T
      cell-induced colitis such that the recipients developed chronic colitis with
      incidence and severity similar to mice generated at LSUHSC. Finally, we found
      that the treatment of mice with preexisting colitis with antibiotics remarkably
      attenuated disease. Taken together, our data demonstrate that specific microbial
      communities determine disease susceptibility and that manipulation of the
      intestinal microbiota alters the induction and/or perpetuation of chronic
      colitis.

PMID- 29361088
TI  - Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.
AB  - Background: Long noncoding RNAs (lncRNA) are key regulators of gene transcription
      and many show tissue-specific expression. We previously defined a novel
      inflammatory and metabolic ileal gene signature in treatment-naive pediatric
      Crohn disease (CD). We now extend our analyses to include potential regulatory
      lncRNA. Methods: Using RNAseq, we systematically profiled lncRNAs and protein
      coding gene expression in 177 ileal biopsies. Co-expression analysis was used to
      identify functions and tissue-specific expression. RNA in situ hybridization was
      used to validate expression. Real-time polymerase chain reaction was used to test
      lncRNA regulation by IL-1beta in Caco-2 enterocytes. Results: We characterize
      widespread dysregulation of 459 lncRNAs in the ileum of CD patients. Using only
      the lncRNA in discovery and independent validation cohorts showed patient
      classification as accurate as the protein-coding genes, linking lncRNA to CD
      pathogenesis. Co-expression and functional annotation enrichment analyses across
      several tissues and cell types 1showed that the upregulated LINC01272 is
      associated with a myeloid pro-inflammatory signature, whereas the downregulated
      HNF4A-AS1 exhibits association with an epithelial metabolic signature. We
      confirmed tissue-specific expression in biopsies using in situ hybridization, and
      validated regulation of prioritized lncRNA upon IL-1beta exposure in
      differentiated Caco-2 cells. Finally, we identified significant correlations
      between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury.
      Conclusions: We systematically define differentially expressed lncRNA in the
      ileum of newly diagnosed pediatric CD. We show lncRNA utility to correctly
      classify disease or healthy states and demonstrate their regulation in response
      to an inflammatory signal. These lncRNAs, after mechanistic exploration, may
      serve as potential new tissue-specific targets for RNA-based interventions.

PMID- 29361090
TI  - Biomarker-Based Models Outperform Patient-Reported Scores in Predicting
      Endoscopic Inflammatory Disease Activity.
AB  - Background: The Crohn's Disease Activity Index (CDAI), a scoring index including
      patient-reported outcomes (PROs), has known limitations for measuring intestinal
      inflammatory disease burden. Noninvasive markers of inflammation could prove more
      accurate than PROs; thus, regulatory authorities are exploring the use of PROs
      and endoscopic data as coprimary end points in clinical trials. The aim of this
      study was to assess the predictive ability of individual components of the CDAI,
      along with biomarker concentrations, to create models for predicting endoscopic
      disease activity. Methods: Between 2004 and 2006, 164 patients with established
      Crohn's disease (CD) undergoing clinically indicated ileocolonoscopy were
      recruited. Individual CDAI variables and fecal calprotectin (FC) were selected to
      explore their predictive accuracy for endoscopic disease activity, with the
      Simple Endoscopic Score-Crohn's Disease (SES-CD) as the outcome variable. Simple
      Poisson regression was performed on each variable, and 2 multivariate models were
      created (PRO-exclusive and PRO+FC [PRO+]). Additional analyses explored the
      patient-level agreement between models. Results: Number of liquid stools,
      abdominal pain, hematocrit (Hct), FC, and high-sensitivity C-reactive protein
      (hsCRP) correlated significantly with the SES-CD. For the prediction of SES-CD
      (>7 vs <=6), the area under the curve (AUC) was 0.81, with 63% and 88%
      sensitivity and specificity, for the PRO+ model, compared with a 0.56 AUC, with
      61% and 55%, respectively, for the PRO model. Intra-individual comparison
      revealed the PRO+ model to be superior in the prediction of endoscopically active
      disease. Conclusions: The inclusion of biomarkers significantly improved
      predictive accuracy for endoscopic disease activity compared with PRO-exclusive
      models.

PMID- 29361091
TI  - Clostridium difficle Enteropathy Is Associated With a Higher Risk for Acute
      Kidney Injury in Patients With an Ileostomy-A Case-Control Study.
AB  - Background: Clostridium difficile infection (CDI) is traditionally considered a
      colon-affecting disease with frequent pseudomembrane formation. However, multiple
      case reports have documented the existence of CDI in the small bowel, and the
      literature on outcome of C difficile enteropathy (CDE) is sparse. The aims of our
      study are to identify risk factors and to assess patient-related outcomes
      associated with CDE. Methods: This is a case-control study involving 112 patients
      at our tertiary care center. Patients with an ileostomy who tested positive for C
      difficile toxins were assigned to the study group (n = 34). The control group
      included patients with an ileostomy who tested negative for the C difficile
      toxins (n = 78). Via chart review, we collected data on baseline characteristics,
      laboratory values, potential risk factors, and outcome measures. Results:
      Patients in the study and control groups were comparable in baseline and
      laboratory characteristics. In univariate analysis, CDE was associated with a
      history of smoking (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.06
      4.3; P = 0.034), the presence of alcohol use (HR, 3.7; 95% CI, 1.05-12.8; P =
      0.042), and older median age at the time of ileostomy (HR, 1.2; 95% CI, 1.07-1.3;
      P = 0.001). In multivariate analysis, no significant association between
      established CDI risk factors (eg, prior exposure to antibiotics and the use of
      proton pump inhibitors or histamine 2 receptor blockers) and the risk for the CDE
      was found. Only a history of alcohol intake was found to be associated with CDE
      (HR, 3.9; 95% CI, 1.09-14.1; P = 0.036). No significant difference in mortality
      was found in the study and control groups (2.9% vs 1.3%, P = 0.52), but patients
      with CDE were more likely to have acute kidney injury (AKI) than those without
      CDE (odds ratio, 4.0; 95% CI, 1.2-13.0. P = 0.023). Conclusions: We identified a
      history of alcohol use a risk factor for CDE. Furthermore, CDE was found be
      associated with an increased risk for developing AKI.

PMID- 29361092
TI  - Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota
      Transplant in Children With Inflammatory Bowel Disease.
AB  - Background: The role of fecal microbiota transplant (FMT) in the treatment of
      pediatric inflammatory bowel disease (IBD) is unknown. The aims of this study
      were to assess safety, clinical response, and gut microbiome alterations in
      children with Crohn's disease (CD), ulcerative colitis (UC), or indeterminate
      colitis (IC). Methods: In this open-label, single-center prospective trial,
      patients with IBD refractory to medical therapy underwent a single FMT by upper
      and lower endoscopy. Adverse events, clinical response, gut microbiome, and
      biomarkers were assessed at baseline, 1 week, 1 month, and 6 months following
      FMT. Results: Twenty-one subjects were analyzed, with a median age of 12 years,
      of whom 57% and 28% demonstrated clinical response at 1 and 6 months post-FMT,
      respectively. Two CD patients were in remission at 6 months. Adverse events
      attributable to FMT were mild to moderate and self-limited. Patients prior to FMT
      showed decreased species diversity and significant microbiome compositional
      differences characterized by increased Enterobacteriaceae, Enterococcus,
      Haemophilus, and Fusobacterium compared with donors and demonstrated increased
      species diversity at 30 days post-FMT. At 6 months, these changes shifted toward
      baseline. Clinical responders had a higher relative abundance of Fusobacterium
      and a lower diversity at baseline, as well as a greater shift toward donor-like
      microbiome after FMT compared with nonresponders. Conclusions: A single FMT is
      relatively safe and can result in a short-term response in young patients with
      active IBD. Responders possessed increased Fusobacterium prior to FMT and
      demonstrated more significant microbiome changes compared with nonresponders
      after FMT. Microbiome characteristics may help in predicting response.

PMID- 29361093
TI  - Postoperative Morbidity Risks Following Ileocolic Resection for Crohn's Disease
      Treated With Anti-TNF Alpha Therapy: A Retrospective Study of 360 Patients.
AB  - Background: Despite the effectiveness of anti-TNF alpha (ATA) treatment to induce
      and maintain remission in Crohn's disease, surgical intervention is frequently
      required. Results of previous studies on the impact of anti-TNF on postoperative
      course are discordant. The aim of this study was to evaluate the impact of ATA on
      postoperative morbidity following ileocolic resection for Crohn's disease.
      Methods: A retrospective review of Crohn's disease patients undergoing ileocolic
      resection was performed. Patients receiving medical treatment <=8 weeks prior to
      surgery were included and followed up for postoperative morbidity. The Clavien
      Dindo classification was used for grading complications. Risk factors for
      postoperative morbidity were assessed on multivariable analysis. Results: A total
      of 360 patients underwent ileocolic resection for Crohn's disease between 2002
      and 2013; 15.3% of patients had ATA <=8 weeks prior to surgery. Laparoscopic
      resections were performed in 110 cases (31%), of which 6% were converted to an
      open operation. Primary anastomosis without the formation of a diverting
      ileostomy was performed in 301 cases. Overall morbidity was 24.2%, with a
      mortality rate of 0.8%. ATA use prior to surgery was identified as an independent
      risk factor for overall morbidity (odds ratio [OR], 2.05; 95% confidence interval
      [CI], 1.08-3.82; P = 0.027) and septic complications (OR, 2.14; 95% CI, 1.03
      4.29; P = 0.04). In subgroup analysis of patients with a primary anastomosis, ATA
      use had no significant impact on septic or overall morbidity. Conclusions:
      Preoperative ATA use is a risk factor for overall postoperative morbidity and
      septic complications. However, the formation of a primary anastomosis should not
      be influenced by preoperative ATA use.

PMID- 29361094
TI  - A Mobile Infliximab Dosing Calculator for Therapy Optimization in Inflammatory
      Bowel Disease.
AB  - Background: Inadequate infliximab (IFX) drug exposure remains a clinical
      challenge and leads to high loss of response rates and therapy failure in
      inflammatory bowel disease (IBD). We aimed to determine the feasibility and pilot
      effectiveness of a novel, web-based, mobile IFX dosing calculator (mIDC) for
      therapy optimization. Methods: We developed an mIDC leveraging the known clinical
      variables of C-reative protein (CRP), albumin, patient's weight, disease activity
      indices, calprotectin, drug trough levels, and antibodies to IFX that
      significantly affect pharmacokinetics and/or outcomes. A prospective
      observational cohort study in pediatric and young adult IBD patients receiving
      maintenance IFX was performed. System-wide practice adoption of mIDC was achieved
      through a quality improvement (QI) initiative within a hospital-based infusion
      unit. Results: Forty-nine patients (median age: 16.0 years; 55% female; 65%
      Crohn's disease) were followed over 9 months. mIDC recommendations for dose
      optimization were followed by the treating physicians in 198 (89%) out of 222
      infusions. Twenty-eight (13%) of 222 mIDC recommendations were to escalate IFX
      dosing; 15 (54%) of 28 escalation recommendations were declined, and these
      patients were more likely to already be receiving IFX dose intensification
      compared with those in whom escalation recommendations were followed (P < 0.05).
      From mIDC initiation to end of follow-up, mean albumin levels remained unchanged
      at 3.8 g/dL. Median CRP remained unchanged at 2 g/L. Median calprotectin levels
      showed a downward trend from 30 to 27 MUg/g (n = 9, P < 0.05). The percentage of
      patients undergoing therapeutic drug monitoring in clinical care increased from
      34% to 86% with the QI initiative. The target median IFX trough goal of >5 MUg/mL
      was achieved with 81% probability throughout the QI initiative, an increase of
      12% compared with pre-QI values. Conclusions: The use of a novel mIDC is feasible
      and potentially effective, facilitating both standardization and
      individualization of therapy in clinical care. mIDC appears to be a practical IFX
      dosing tool for point-of-care use, leveraging individual pharmacokinetic
      considerations.

PMID- 29361095
TI  - Changing Infliximab Prescription Patterns in Inflammatory Bowel Disease: A
      Population-Based Cohort Study, 1999-2014.
AB  - Background: Long-term data on real life use of infliximab (IFX) for inflammatory
      bowel disease (IBD) are lacking. We studied prescription patterns during the
      first 16 years following marketing authorization. Methods: In a population-based
      cohort from the North Denmark Region, all IBD patients exposed to IFX during 1999
      to 2014 were identified. Results: A total of 623 patients (210 with ulcerative
      colitis [UC] and 413 with Crohn's disease [CD]) were exposed to IFX. In patients
      with UC, age at first exposure decreased by 10 months per calendar year (P <
      0.05) during the study period. In patients with CD, disease duration at time of
      first IFX exposure decreased by 7 months per calendar year (P < 0.001). From 2005
      2009 to 2010-2014, the proportion of IFX-exposed patients with pancolitis (40% vs
      24%, P = 0.04) and the proportion of patients with extensive CD (P = 0.002)
      decreased. The mean time to discontinuation of IFX remained stable in patients
      with CD during the study period (2.5-3.0 years) and increased from 0.34 years
      (2005-2009) to 1.11 years (2010-2015) in patients with UC (P = 0.04). Conclusion:
      During the first 16 years postmarketing, age at first exposure to IFX decreased
      in patients with UC, whereas disease duration at time of first exposure decreased
      in patients with CD. Also, a significant change toward less extensive disease in
      both UC and CD patients exposed to IFX was observed. Treatment duration in
      patients with UC increased during the study period, but did not reach the more
      constant and longer duration of treatment observed in patients with CD.

PMID- 29361096
TI  - Reliability of Measuring Ileo-Colonic Disease Activity in Crohn's Disease by
      Magnetic Resonance Enterography.
AB  - Background: Magnetic resonance enterography is increasingly utilized for
      assessment of luminal Crohn's disease activity. The Magnetic Resonance Index of
      Activity and the London Index are the most commonly used outcome measures in
      clinical trials. We assessed the reliability of these indices and several
      additional items. Methods: A consensus process clarified scoring conventions and
      identified additional items based on face validity. Four experienced radiologists
      evaluated 50 images in triplicate, in random order, at least 1 month apart, using
      a central image management system. Intra- and interrater reliability were
      assessed by calculating and comparing intraclass correlation coefficients.
      Results: Intrarater intraclass correlation coefficients (95% confidence
      intervals) for the Magnetic Resonance Index of Activity, London, and London
      "extended" indices and a visual analogue scale were 0.89 (0.84 to 0.91), 0.87
      (0.83 to 0.90), 0.89 (0.85 to 0.92), and 0.86 (0.81 to 0.90). Corresponding
      interrater intraclass correlation coefficients were 0.71 (0.61 to 0.77), 0.67
      (0.55 to 0.75), 0.70 (0.61 to 0.76), and 0.71 (0.62 to 0.77). Reliability for
      each index was greatest in the terminal ileum and poorest in the rectum. All 3
      indices were highly correlated with the visual analogue scale; 0.79 (0.71 to
      0.85), 0.78 (0.71 to 0.84), and 0.79 (0.72 to 0.85) for the Magnetic Resonance
      Index of Activity, London, and the London "extended" indices, respectively.
      Conclusions: "Substantial" interrater reliability was observed for all 3 indices.
      Future studies should assess responsiveness to treatment in order to confirm
      their utility as evaluative indices in clinical trials and clinical practice.

PMID- 29361097
TI  - Health-Related Quality of Life and Work-Related Outcomes for Patients With Mild
      to-Moderate Ulcerative Colitis and Remission Status Following Short-Term and Long
      Term Treatment With Multimatrix Mesalamine: A Prospective, Open-Label Study.
AB  - Background: Disease activity of patients with ulcerative colitis (UC) predicts
      health-related quality of life (HRQL) and work-related outcomes (eg, absenteeism,
      productivity). We tested whether outcomes differed among patients in complete
      (clinical and endoscopic) remission, partial remission, or not in remission
      following treatment with multimatrix mesalamine. Methods: Data were from an open
      label, multicountry, prospective trial (ClinicalTrials.gov identifier:
      NCT01124149) of 717 adults with active mild-to-moderate UC treated with 4.8 g/day
      multimatrix mesalamine tablets for 8 weeks (induction period); 459 patients who
      achieved partial or complete remission received daily 2.4 g/day multimatrix
      mesalamine for 12 additional months (maintenance period). HRQL (SF-12v2 Health
      Survey and Short Inflammatory Bowel Disease Questionnaire) and work-related
      outcomes (Work Productivity and Activity Impairment questionnaire) were assessed
      at baseline and final visits of each treatment period. Differences in scores by
      remission status within each treatment period were tested using analysis of
      variance and analysis of covariance models, whereas mixed-effects models with
      repeated measures tested changes over time. Results: At their final visit of each
      treatment period, patients in partial remission scored significantly better on
      all HRQL and work-related domains than patients not in remission (all Bonferroni
      adjusted P < 0.05). Scores for patients in partial remission were, almost without
      exception, statistically equivalent to those for patients in complete remission.
      Fluctuating between complete and partial remission during maintenance treatment
      had no impact on outcomes. Conclusions: Patients in partial remission following
      multimatrix mesalamine treatment had HRQL and work-related outcomes equivalent to
      patients in complete remission. Achievement and maintenance of partial remission
      may be sufficient for improvements in patients' functioning, well-being, and work
      performance.

PMID- 29361099
TI  - It's Too Soon to Count Out Vedo for Postoperative Crohn's Disease.

PMID- 29361098
TI  - Patient Decision-Making About Emergency and Planned Stoma Surgery for IBD: A
      Qualitative Exploration of Patient and Clinician Perspectives.
AB  - Background: Many inflammatory bowel disease (IBD) patients worry about stoma
      forming surgery (SFS), sometimes enduring poor bowel-related quality of life to
      avoid it. Anticipation of SFS and whether expectations match experience is
      underreported. This qualitative study explored influences on patients' SFS
      decision-making and compared preoperative concerns with postoperative outcomes.
      Methods: We purposively recruited participants with IBD from UK hospital
      outpatient and community sources, and IBD clinicians from public hospitals. Four
      focus groups, 29 semistructured patient participant interviews, and 18 clinician
      interviews were audio recorded, transcribed, and analysed thematically.
      Participants had a current temporary, recently-reversed, or permanent stoma, or
      were stoma naive. Results: Four themes emerged: Preoperative concerns and
      expectations, Patient decision-making, Surgery and recovery, and Long-term
      outcomes. Participants and clinicians agreed about most preoperative concerns,
      that outcomes were often better than expected, and support from others with a
      stoma is beneficial. Patient decision-making involves multiple factors, including
      disease status. Some clinicians avoid discussing SFS, and the phrase 'last
      resort' can bias patient perceptions; others recommend early discussion,
      increasing dialogue when medical management becomes ineffective. The
      postoperative period is particularly challenging for patients. Stoma acceptance
      is influenced by personal perceptions and pre- and postoperative clinical and
      social support. Conclusion: Patients need balanced information on all treatment
      options, including surgery, from an early stage. Early multidisciplinary team
      dialogue about SFS, and contact with others living well with a stoma, could
      enable informed decision-making. Life with a stoma is often better than
      anticipated, improving quality of life and control. Ongoing specialist nursing
      support aids recovery and adjustment.

PMID- 29361100
TI  - Assessing the Optimal Position for Vedolizumab in the Treatment of Ulcerative
      Colitis: A Simulation Model.
AB  - Background: Vedolizumab, an alpha4beta7 integrin monoclonal antibody inhibiting
      gut lymphocyte trafficking, is an effective treatment for ulcerative colitis
      (UC). We evaluated the optimal position of vedolizumab in the UC treatment
      paradigm. Methods: Using Markov modeling, we assessed multiple algorithms for the
      treatment of UC. The base case was a 35-year-old male with steroid-dependent
      moderately to severely active UC without previous immunomodulator or biologic
      use. The model included 4 different algorithms over 1 year, with vedolizumab use
      prior to: initiating azathioprine (Algorithm 1), combination therapy with
      infliximab and azathioprine (Algorithm 2), combination therapy with an
      alternative anti-tumor necrosis factor (anti-TNF) and azathioprine (Algorithm 3),
      and colectomy (Algorithm 4). Transition probabilities and quality-adjusted life
      year (QALY) estimates were derived from the published literature. Primary
      analyses included simulating 100 trials of 100,000 individuals, assessing
      clinical outcomes, and QALYs. Sensitivity analyses employed longer time horizons
      and ranges for all variables. Results: Algorithm 1 (vedolizumab use prior to all
      other therapies) was the preferred strategy, resulting in 8981 additional
      individuals in remission, 18 fewer cases of lymphoma, and 1087 fewer serious
      infections per 100,000 patients compared with last-line use (A4). Algorithm 1
      also resulted in 0.0197 to 0.0205 more QALYs compared with other algorithms. This
      benefit increased with longer time horizons. Algorithm 1 was preferred in all
      sensitivity analyses. Conclusion: The model suggests that treatment algorithms
      positioning vedolizumab prior to other therapies should be considered for
      individuals with moderately to severely active steroid-dependent UC. Further
      prospective research is needed to confirm these simulated results.

PMID- 29361101
TI  - Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis
      and Crohn's Disease-Like Complications of the Pouch After Ileal Pouch-Anal
      Anastomosis Following Colectomy for Ulcerative Colitis.
AB  - Background: Inflammatory complications including chronic refractory pouchitis and
      Crohn's disease (CD)-like complications of the pouch are common complications
      after ileal pouch-anal anastomosis (IPAA) following colectomy for ulcerative
      colitis (UC). We performed a systematic review and meta-analysis to evaluate the
      efficacy of anti-TNF therapy in distinguishing patients with chronic refractory
      pouchitis from those with CD-like complications of the pouch. Methods: We
      performed a systematic literature search to identify articles and abstracts
      reporting anti-TNF agents efficacy in treating inflammatory complications of the
      pouch after IPAA for UC. Short-term and long-term remissions were evaluated at 8
      weeks 95%CI[5-10] and 12 months 95%CI[12-18.5], respectively. Results: We
      identified 21 articles and 3 abstracts including 313 patients treated either with
      infliximab (n = 194) or adalimumab (n = 119) for inflammatory complications of
      the pouch. The rates of short-term and long-term clinical remission were 0.50
      (95%CI [0.37-0.63]; I2 = 0.57) and 0.52 (95%CI[0.39-0.65]; I2 = 0.59),
      respectively. The rate of remission after anti-TNF induction therapy seemed to be
      higher in CD-like complications of the pouch 0.64 (95%CI[0.5-0.77]; I2 = 0.18),
      compared to refractory pouchitis 0.10 (95%CI [0.00-0.35]; I2 = 0.00) (P = 0.06),
      whereas no such difference appeared after long-term maintenance therapy 0.57
      (95%CI[0.43-0.71]; I2 = 0.32) and 0.37 (95%CI [0.14-0.62]; I2 = 0.47),
      respectively (P = 0.57). Sensitivity analyses suggested no difference in
      outcomes. No significant publication bias has been detected. Conclusion: Anti-TNF
      agents have a clear trend to have higher and faster efficacy in CD-like
      complications of the pouch compared to refractory pouchitis, highlighting the
      need to differentiate these two entities both in daily practice and clinical
      trials.

PMID- 29361103
TI  - Reviewing the Risk of Colorectal Cancer in Inflammatory Bowel Disease After Liver
      Transplantation for Primary Sclerosing Cholangitis.
AB  - The presence of concomitant primary sclerosing cholangitis (PSC) with
      inflammatory bowel disease (IBD) represents a distinct disease phenotype that
      carries a higher risk of colorectal cancer (CRC) than the average IBD patient.
      Given that liver transplantation (LT) is the only treatment that offers a
      survival benefit in PSC patients with hepatic dysfunction, management decisions
      in IBD patients' post-LT for PSC are frequently encountered. One such
      consideration is the risk of CRC in this immunosuppressed cohort. With most
      studies showing an increased risk of CRC post-LT in these IBD patients, a closer
      look at the associated risk factors of CRC and the adopted surveillance
      strategies in this subset of patients is warranted. Low-dose ursodeoxycholic acid
      has shown a potential chemopreventive effect in PSC-IBD patients pre-LT; however,
      a favorable effect remains to be seen in post-LT group. Also, further studies are
      necessary to assess the benefit of 5 aminosalicylate therapy. Annual surveillance
      colonoscopy in the post-LT period is recommended for PSC-IBD patients subset
      given their high risk for CRC.

PMID- 29361102
TI  - Sexual Dysfunction in Men With Inflammatory Bowel Disease: A New IBD-Specific
      Scale.
AB  - Background: Men with inflammatory bowel disease (IBD) may have increased sexual
      dysfunction. To measure the prevalence of sexual dysfunction in our male
      patients, we aimed to develop a new IBD-specific Male Sexual Dysfunction Scale
      (the IBD-MSDS). Methods: We used a cross-sectional survey and enrolled male
      patients (N = 175) >=18 years old who attended IBD clinics at 2 Boston hospitals.
      We collected information on sexual functioning via a 15-item scale. General male
      sexual functioning was measured using the International Index of Erectile
      Dysfunction (IIEF); the Patient Health Questionnaire (PHQ-9) measured depressive
      symptoms. Medical history and sociodemographic information were extracted from
      medical record review. Exploratory factor analyses (EFA) assessed
      unidimensionality, factor structure, reliability, and criterion and construct
      validity of the 15-item scale. We used regression models to identify clinical
      factors associated with sexual dysfunction. Results: EFA suggested retaining 10
      items generating a unidimensional scale with strong internal consistency
      reliability, alpha = 0.90. Criterion validity assessed using Spearman's
      coefficient showing that the IBD-MSDS was significantly correlated with all the
      subscales of the IIEF. The IBD-MSDS was significantly correlated (construct
      validity) with the PHQ-9 (P < 0.001) and the composite score for active IBD cases
      (P < 0.05). Male sexual dysfunction in IBD was significantly associated with the
      presence of an ileoanal pouch anastomosis (P = 0.047), depression (P < 0.001),
      and increased disease activity (P = 0.021). Conclusions: We have developed and
      validated an IBD-specific scale to assess the psychosexual impact of IBD. This
      new survey tool may help physicians screen for and identify factors contributing
      to impaired sexual functioning in their male patients.

PMID- 29361105
TI  - Interventional IBD: The Role of Endoscopist in the Multidisciplinary Team
      Management of IBD.
AB  - Inflammatory bowel disease (IBD) has been traditionally managed by IBD medical
      doctors or IBDologists and colorectal surgeons. Complications related to IBD and
      IBD surgery, such as stricture, fistula, and abscess, are common. For the past
      decade, endoscopic therapy has emerged as a valid treatment option for those
      complications. Endoscopic therapy provides more effective therapy for those
      structural complications than medical treatment, while being a less invasive
      approach than surgery. Endoscopic therapy plays a growing role in bridging
      medical and surgical therapies and is becoming an important component in the
      multidisciplinary approach to complex IBD. In fact, endoscopic therapy has become
      the treatment of choice for anastomotic stricture and anastomotic sinus. The role
      of endoscopic resection of colitis-associated neoplasia is currently being
      explored. Interventional IBD is intellectually and technically challenging. We
      are calling for proper teaching and training of our next generation of IBD
      interventionists.

PMID- 29361104
TI  - Sports Participation in Youth With Inflammatory Bowel Diseases: The Role of
      Disease Activity and Subjective Physical Health Symptoms.
AB  - Background: Physical activity is important for youth with inflammatory bowel
      diseases (IBD), and sports participation is a common way in which youth are
      physically active. Yet, studies examining sports participation in youth with IBD
      and barriers to sports participation are lacking. This study examined the role of
      disease complications, body mass index (BMI), subjective physical health, and
      psychosocial functioning in influencing sports participation in a large sample of
      youth with IBD participating in the Crohn's and Colitis Foundation of America
      Partners (CCFA Partners) Kids and Teens Registry. Methods: CCFA Partners Kids and
      Teens is an internet-based cohort study in which participants and their parents
      self-report demographics, disease characteristics, anthropometrics, and validated
      assessments of physical health, psychosocial functioning, and perceived
      impairment in sports participation. We performed a cross-sectional analysis of
      450 cohort participants, age 12-17 years. Results: Nearly two-thirds of the
      sample reported that their IBD resulted in some impairment in sports
      participation. IBD disease activity was associated with perceived impairment in
      sports participation. In a forward regression analysis controlling for disease
      activity, fatigue, pain, and past IBD-related surgery emerged as the most salient
      correlates of impairment in sports participation. Conclusions: Disease activity
      and subjective physical health symptoms were the most salient correlates of
      impairment in sports participation. Whether these barriers interfere with
      physical activity more generally deserves further study, as does replication of
      these findings longitudinally. Ultimately, a greater understanding of potential
      barriers to sports participation may be useful for generating targeted physical
      activity recommendations for youth with IBD.

PMID- 29361106
TI  - Disagreement Among Gastroenterologists Using the Mayo and Rutgeerts Endoscopic
      Scores.
AB  - Background: Endoscopy is routinely performed in patients with inflammatory bowel
      disease to evaluate disease severity and guide important clinical decisions.
      However, variability in the interpretation of endoscopic findings can
      significantly impact patient management. Methods: Fifty-eight gastroenterologists
      were invited to participate in an online survey including pictures and video
      recordings of colonoscopies performed in patients with ulcerative colitis (UC)
      and Crohn's disease (CD). Participants were asked to rate the colorectal mucosa
      in patients with UC using the Mayo endoscopic subscore (MES), and the neo
      terminal ileum and anastomosis in operated patients with CD using the Rutgeerts
      score (RS). Overall interrater agreement (IRA) and for several key end points was
      assessed using Krippendorff's alpha test. Results: The IRAs for the MES and RS
      were 0.47 (95% confidence interval [CI], 0.41-0.54) and 0.33 (95% CI, 0.28-0.38).
      The IRAs for UC mucosal healing (MES <= 1) and complete mucosal healing (MES = 0)
      were 0.57 (95% CI, 0.40-0.72) and 0.89 (95% CI, 0.73-1) and for CD postoperative
      recurrence (RS >= i2), and IRAs for severe postoperative recurrence (RS >= 3)
      were 0.44 (95% CI, 0.24-0.62) and 0.54 (95% CI, 0.36-0.71), respectively.
      Unexpectedly, although clinical information significantly influenced the IRA,
      participant expertise and consultation of scores did not produce significant
      changes in the IRA. Conclusions: A high rate of disagreement in endoscopic
      scoring was found in this study, even among experienced physicians. The
      variability in the assessment of mucosal healing and postoperative recurrence may
      translate into relevant differences in patient management.

PMID- 29361107
TI  - Effects of sleep deprivation on component processes of working memory in younger
      and older adults.
AB  - Study Objectives: Working memory (WM) has been described as a multicomponent
      process, comprised of the following: attention-driven encoding, maintenance and
      rehearsal of information, and encoding to and retrieval from episodic memory.
      Impairments can affect higher-order cognitive processes and many everyday
      functions. The impact of sleep changes on these cognitive processes across the
      life span needs to be investigated. The aim of the current study is to examine
      the effects of sleep deprivation on component processes of WM, comparing younger
      and older adults across verbal and visuospatial modalities. Methods: Thirty-one
      younger adults (19-38 years) and 33 older adults (59-82 years) attended two
      counterbalanced sleep protocols: a regular night of sleep followed by testing the
      next day (normally rested condition), and 36 hr of total sleep deprivation (TSD),
      followed by testing (TSD condition). Participants completed matched versions of
      verbal and visuospatial WM tasks across conditions. Results: Younger adults
      significantly outperformed older adults on encoding and displacement component
      processes, for both verbal and visuospatial WM. Following TSD, younger adults
      showed a significantly larger drop compared with older adults in verbal encoding
      and in visuospatial displacement. A main effect of condition was observed for
      verbal displacement. Conclusions: Differences were observed in the performance of
      younger and older adults on component processes of WM following TSD. This
      suggests that TSD can have differential effects on each component process when
      younger and older adults are compared, in both verbal and visuospatial tasks.
      Understanding this profile of changes is important for the development of
      possible compensatory strategies or interventions and the differentiation of
      clinical and healthy populations.

PMID- 29361108
TI  - The effect of refined functional carbohydrates from enzymatically hydrolyzed
      yeast on the transmission of environmental Salmonella Senftenberg among broilers
      and proliferation in broiler housing.
AB  - Hatching eggs collected from resident broiler breeders at 48 wk of age were used
      to produce male and female chicks that were assigned sex separately to 96 new
      litter pens and fed either a 0 or 50 g/MT RFC (refined functional carbohydrate
      feed additive derived from yeast) diet. There were 24 replicate pens of 12
      broilers each per diet per sex. Feed intake and BW were determined at 14, 28, and
      42 d of age. Litter was sampled by pen using sterile socks at 35 d and tested for
      Salmonella spp. using an enzyme linked fluorescence assay method. Salmonella spp.
      was isolated from 7 of 48 control-fed broiler pens but no RFC-fed pens (P <=
      0.05). Thereafter, 48 males and 48 females were selected based on litter
      Salmonella presence and RFC treatment. The cecas of these broilers were
      aseptically excised after feed withdrawal and lairage and tested for presence of
      Salmonella spp. There were 18 of the 48 control-fed broilers confirmed positive
      from litter-positive pens but none from litter-negative pens fed RFC. The serovar
      of litter and cecal Salmonella isolates was Salmonella enterica subsp. enterica
      serovar Senftenberg (S. Senftenberg). Female broilers that were fed RFC exhibited
      greater BW at 28 d (P <= 0.05) and 42 d (P <= 0.05) while RFC-fed males exhibited
      improved feed efficiency during the 15-28 d period (P = 0.06). These data
      demonstrated that dietary RFC reduced the prevalence of Salmonella in the litter
      and ceca of broilers when fed continuously while not being detrimental to broiler
      live performance.

PMID- 29361109
TI  - MEASUREMENTS OF THE PARASITIC NEUTRON DOSE AT ORGANS FROM MEDICAL LINACS AT
      DIFFERENT ENERGIES BY USING BUBBLE DETECTORS.
AB  - Conventional linear accelerators (LINACs) for radiotherapy produce fast secondary
      neutrons due to photonuclear processes. The neutron presence is considered as an
      extra undesired dose during the radiotherapy treatment, which could cause
      secondary radio-induced tumors and malfunctions to cardiological implantable
      devices. It is thus important to measure the neutron dose contribution to
      patients during radiotherapy, not only at high-energy LINACs, but also at lower
      energies, near the giant dipole resonance reaction threshold. In this work, the
      full body neutron dose equivalent has been measured during single-field
      radiotherapy sessions carried out at different LINAC energies (15, 10 and 6 MV)
      by using a tissue equivalent (for neutrons) anthropomorphic phantom together with
      bubble dosemeters. Results have shown that some neutron photoproduction is still
      present also at lower energies. As a consequence, emitted photoneutrons cannot be
      ignored and represent a risk contribution for patients undergoing radiotherapy.

PMID- 29361110
TI  - COMMITTED EFFECTIVE DOSE DUE TO THE INTAKE OF 40K, 226Ra, 228Ra AND 228Th
      CONTAINED IN FOODS INCLUDED IN THE DIET OF THE RIO DE JANEIRO CITY POPULATION,
      BRAZIL.
AB  - Annual effective dose due to the consumption of 40K, 226Ra, 228Ra and 228Th was
      estimated from high-resolution gamma spectrometry, food consumption data for the
      inhabitants of Rio de Janeiro City and dose coefficients published by the ICRP
      119. A total of 31 samples of cereals, grains, vegetables, flours, liquid and
      perishables were analyzed. 40K was measured in all samples, and bean sample
      presented highest specific concentration 489.36 +/- 23.70 Bq kg-1. The highest
      specific concentration for 226Ra, 228Ra and 228Th was measured in pumpkin (7.82
      +/- 1.09 Bq kg-1), carrot (30.18 +/- 1.99 Bq kg-1) and beet (2.43 +/- 0.48 Bq kg
      1), respectively. The highest contribution to annual effective dose came from
      beans (556.3 MUSv), potato (12.5 MUSv), carrot (10.3 MUSv), banana (4.7 MUSv) and
      beet (3.3 MUSv). It was observed that updates of daily food consumption values
      was the main reason for an up to 10-fold difference between the annual effective
      dose found in the present study and literature data.

PMID- 29361111
TI  - Epidemiological Data on the Effectiveness of Influenza Vaccine-Another Piece of
      the Puzzle.

PMID- 29361112
TI  - What is new in pain modification in osteoarthritis?
AB  - There is a big need for the development of novel therapies for the safe
      management of chronic pain associated with OA. Here we reviewed PubMed (2015
      onward) and ClinicalTrials.gov for ongoing and recently completed trials where
      pain in OA is the primary outcome measure. Three broad categories were
      identified: biological therapies, small molecules and cryoneurolysis. The most
      promising new strategy is blockade of nerve growth factor with antibodies. Two
      anti-nerve growth factor antibodies, tanuzemab and fasinumab, are in active
      development after the 2010 hold on trials was lifted in 2015. In addition,
      several active clinical trials are testing distinct mechanism-based
      interventions, including cytokine inhibition, selective MU, delta or kappa opioid
      receptor agonists, zoledronate and intra-articular capsaicin. In addition to
      pharmacological approaches, cryoneurolytic strategies that directly target
      peripheral nerves may play a role in OA pain management, but efficacy profiles
      and long-term effects of such treatments need more study. Clearly, the
      therapeutic landscape for OA pain is rapidly expanding. Since symptomatic OA is a
      heterogeneous disease, the challenge will be to identify patients that will
      benefit the most from specific approaches.

PMID- 29361113
TI  - Repellent Effects of Insecticides Against Protaphorura fimata (Collembola:
      Poduromorpha: Onychiuridae).
AB  - Protaphorura fimata Gisin (Poduromorpha: Onychiuridae) is a serious pest of
      lettuce [Lactuca sativa L. (Asteraceae)] in the Salinas Valley of California.
      Because P. fimata is a subterranean springtail species adapted to soil
      environments, individuals are assumed to be able to sense and behaviorally avoid
      insecticide-treated soil, and this capacity could be used strategically to
      control P. fimata. A series of laboratory bioassays was conducted to examine the
      behavior of P. fimata with respect to insecticides via noncontact and contact
      assays. In the noncontact assay, significantly more P. fimata individuals were
      collected away from the insecticide source than closer to the source (P < 0.05)
      when clothianidin, flonicamid, bifenthrin, diamethoate, essential oils, extracts
      of C. subtsugae, methomyl, chlorpyrifos, zeta-cypermethrin, thiamethoxam,
      pyrethrins, extracts of Burkholderia spp., cyantraniliprole, and oxamyl were used
      as insecticides. In the contact assay, P. fimata individuals spent significantly
      less time on discs treated with spinetoram and lambda-cyhalothrin during each
      crossing than on flonicamid- and oxamyl-treated discs. P. fimata individuals
      changed direction more frequently while crossing discs when the discs were
      treated with azadirachtin, clothianidin, bifenthrin, thiamethoxam +
      chlorantraniliprole, chlorpyrifos, cyantraniliprole, and lambda-cyhalothrin than
      when they were treated with water. In another contact assay, the number of
      seedlings injured by P. fimata feeding was significantly lower when germinating
      seeds were enclosed in a barrier treated with clothianidin, chlopyrifos,
      pyrethrins, and cyantraniliprole than when they were enclosed in a spinosad
      treated barrier. The implications of these data for P. fimata management in the
      Salinas Valley are discussed.

PMID- 29361114
TI  - Molecular diagnostics in FUO.

PMID- 29361115
TI  - The GATA transcription factor ELT-2 modulates both the expression and
      methyltransferase activity of PRMT-1 in Caenorhabditis elegans.
AB  - Protein arginine methyltransferase 1 (PRMT1) catalyzes asymmetric arginine
      dimethylation of cellular proteins and thus modulates various biological
      processes, including gene regulation, RNA metabolism, cell signaling and DNA
      repair. Since prmt-1 null mutant completely abolishes asymmetric dimethylarginine
      in C. elegans, PRMT-1 is thought to play a crucial role in determining levels of
      asymmetric arginine dimethylation. However, the mechanism underlying the
      regulation of PRMT-1 activity remains largely unknown. Here, we explored for
      transcription factors that induce the expression of PRMT-1 by an RNAi screen
      using transgenic C. elegans harbouring prmt-1 promoter upstream of gfp. Of 529
      clones, we identify a GATA transcription factor elt-2 as a positive regulator of
      Pprmt-1:: gfp expression and show that elt-2 RNAi decreases endogenous PRMT-1
      expression at mRNA and protein levels. Nevertheless, surprisingly arginine
      methylation levels are increased when elt-2 is silenced, implying that erythroid
      like transcription factor (ELT)-2 may also have ability to inhibit
      methyltransferase activity of PRMT-1. Supporting this idea, GST pull-down and co
      immunoprecipitation assays demonstrate the interaction between ELT-2 and PRMT-1.
      Furthermore, we find that ELT-2 interferes with PRMT-1-induced arginine
      methylation in a dose-dependent manner. Collectively, our results illustrate the
      two modes of PRMT-1 regulation, which could determine the levels of asymmetric
      arginine dimethylation in C. elegans.

PMID- 29361116
TI  - Efficient development of a stable cell pool for antibody production using a
      single plasmid.
AB  - Therapeutic antibodies are the fastest growing group of biopharmaceuticals.
      Evaluation of drug candidates requires a sufficient amount of antibodies.
      Production of antibodies with stable cell pools is an efficient strategy to
      produce grams of proteins for drug candidate selection. Many methods have been
      described for developing stable cell pools for antibody expression. However, most
      of the reported methods are laborious due to the low frequency of high producers.
      In this study, we determined optimal vectors and screening parameters to develop
      a strategy for efficient construction of stable antibody expressing cell pools.
      The cell pool constructed using the optimized strategy consistently yielded a
      higher expression titer, up to 10-fold improvement. Further, this method resulted
      in a higher ratio of the cell pools with the main product peak above 95% as
      assessed by size-exclusion chromatography. High producers could be obtained by
      means of screening five 96-well plates. This strategy will greatly reduce clone
      screening size during Clinical Lead Selection. This study provides a platform
      with efficient design of plasmids and screening strategies for significant cost
      and labour savings in high expression of two-subunit proteins such as antibodies.

PMID- 29361117
TI  - Discrepancy Between Low Levels of mTOR Activity and High Levels of P-S6 in
      Primary Central Nervous System Lymphoma May Be Explained by PAS Domain-Containing
      Serine/Threonine-Protein Kinase-Mediated Phosphorylation.
AB  - The primary aim of this study was to determine mTOR-pathway activity in primary
      central nervous system lymphoma (PCNSL), which could be a potential target for
      therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity,
      we aimed to identify other pathways that may lead to S6 phosphorylation. We
      measured mTOR activity with immunohistochemistry for p-mTOR and its downstream
      effectors p(T389)-p70S6K1, p-S6, and p-4E-BP1 in 31 cases of PCNSL and 51 cases
      of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6
      phosphorylation pathways with p-RSK, p(T229)-p70S6K1, and PASK antibodies.
      Finally, we examined the impact of PASK inhibition on S6 phosphorylation on BHD1
      cell line. mTOR-pathway activity was significantly less frequent in PCNSL
      compared with DLBCL. p-S6 positivity was related to mTOR-pathway in DLBCL, but
      not in PCNSL. Among the other kinases potentially responsible for S6
      phosphorylation, PASK proved to be positive in all cases of PCNSL and DLBCL.
      Inhibition of PASK resulted in reduced expression of p-S6 in BHD1-cells. This is
      the first study demonstrating an mTOR independent p-S6 activity in PCNSL and that
      PASK may contribute to the phosphorylation of S6. Our findings also suggest a
      potential role of PASK in the pathomechanism of PCNSL and in DLBCL.

PMID- 29361120
TI  - Sexual Competitiveness, Field Survival, and Dispersal of Anastrepha obliqua
      (Diptera: Tephritidae) Fruit Flies Irradiated at Different Doses.
AB  - The sterile insect technique (SIT) is used in area-wide pest management programs
      for establishing low pest prevalence and/or areas free of fruit flies (Diptera:
      Tephritidae). The aim of this technique is to induce high levels of sterility in
      the wild population, for this the released insects must have a high sexual
      competitiveness and field dispersal. However, radiation decreases these
      biological attributes that do not allow it to compete successfully with wild
      insects. In this study the sexual competitiveness, field survival and dispersal
      of Anastrepha obliqua (Macquart; Diptera: Tephritidae) irradiated at 0, 40, 50,
      60, 70, and 80 Gy were evaluated in laboratory. A dose of 60 Gy produced 98%
      sterility, whereas doses of 70 and 80 Gy produced 99% sterility. Sexual
      competitiveness was assessed in field cages, comparing males irradiated at 0, 50,
      60, 70, and 80 Gy against wild males for mating with wild fertile females. Males
      irradiated at 50 and 60 Gy achieved more matings than those irradiated at 70 and
      80 Gy. Wild males were more competitive than mass-reared males, even when these
      were not irradiated (0 Gy). There was no effect of irradiation on mating latency,
      yet wild males showed significantly shorter mating latency than mass-reared
      males. Female remating did not differ among those that mated with wild males and
      those that mated with males irradiated with different doses. The relative
      sterility index (RSI) increased from 0.25 at 80 Gy to 0.37 at 60 Gy. The Fried
      competitiveness index was 0.69 for males irradiated at 70 Gy and 0.57 for those
      irradiated at 80 Gy, which indicates that a 10 Gy reduction in the irradiation
      dose produces greater induction of sterility in the wild population. There were
      no significant differences in field survival and dispersal between flies
      irradiated at 70 or 80 Gy. Reducing the irradiation dose to 60 or 70 Gy could
      improve the performance of sterile males and the effectiveness of the SIT. Our
      results also distinguish between the effects of irradiation and mass-rearing on
      the performance of sterile males.

PMID- 29361119
TI  - Imaging fibroblast activation protein to monitor therapeutic effects of
      neutralizing interleukin-22 in collagen-induced arthritis.
AB  - Objectives: RA is a chronic autoimmune disease leading to progressive destruction
      of cartilage and bone. RA patients show elevated IL-22 levels and the amount of
      IL-22-producing Th cells positively correlates with the extent of erosive
      disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of
      this study was to determine the feasibility of SPECT/CT imaging with 111In
      labelled anti-fibroblast activation protein antibody (28H1) to monitor the
      therapeutic effect of neutralizing IL-22 in experimental arthritis. Methods: Mice
      (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To
      monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h
      after injection of 111In-28H1. Imaging results were compared with macroscopic,
      histologic and radiographic arthritis scores. Results: Neutralizing IL-22 before
      CIA onset effectively prevented arthritis development, reaching a disease
      incidence of only 50%, vs 100% in the control group. SPECT imaging showed
      significantly lower joint tracer uptake in mice treated early with anti-IL-22
      antibodies compared with the control-treated group. Reduction of disease activity
      in those mice was confirmed by macroscopic, histological and radiographic
      pathology scores. However, when treatment was initiated in a later phase of CIA,
      progression of joint pathology could not be prevented. Conclusion: These findings
      suggest that IL-22 plays an important role in CIA development, and neutralizing
      this cytokine seems an attractive new strategy in RA treatment. Most importantly,
      SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy
      responses, and is potentially more sensitive in disease monitoring than the gold
      standard method of macroscopic arthritis scoring.

PMID- 29361118
TI  - Assessment of Circulating Tumor Cells as a Predictive Biomarker of Histology in
      Women With Suspected Ovarian Cancer.
AB  - Background: The clinical assessment of circulating tumor cells (CTCs) as a blood
      based biomarker is FDA-approved for use in breast, colorectal, and prostate
      cancers. The objective of this prospective clinical study was to determine
      whether pretreatment CTCs are a useful diagnostic biomarker in women with complex
      pelvic masses. Methods: Whole blood was collected from 49 women with newly
      diagnosed pelvic masses. The presence of CTCs was compared between women with and
      without ovarian cancer histopathologic diagnosis after surgery using a Chi
      squared test. Results: CTCs were absent in those with benign disease (0/14),
      present in 17% (5/29) of patients with a histologic diagnosis of ovarian
      carcinoma, and present in 80% (4/5) of patients with ovarian metastases from
      other cancers (P = 0.001). All 5 women with ovarian cancer who had CTCs present
      presented stage III or IV of the disease (P = 0.13). Conclusions: CTCs were more
      prevalent in patients with metastases to the ovary than in primary ovarian
      carcinomas.

PMID- 29361121
TI  - A New Gastric Cancer Among Us.

PMID- 29361122
TI  - Multiplatform next-generation sequencing identifies novel RNA molecules and
      transcript isoforms of the endogenous retrovirus isolated from cultured cells.
AB  - In this study, we applied short- and long-read RNA sequencing techniques, as well
      as PCR analysis to investigate the transcriptome of the porcine endogenous
      retrovirus (PERV) expressed from cultured porcine kidney cell line PK-15. This
      analysis has revealed six novel transcripts and eight transcript isoforms,
      including five length and three splice variants. We were able to establish
      whether a deletion in a transcript is the result of the splicing of mRNAs or of
      genomic deletion in one of the PERV clones. Additionally, we re-annotated the
      formerly identified RNA molecules. Our analysis revealed a higher complexity of
      PERV transcriptome than it was earlier believed.

PMID- 29361123
TI  - Quantitative super-resolution single molecule microscopy dataset of YFP-tagged
      growth factor receptors.
AB  - Background: Super-resolution single molecule localization microscopy (SMLM) is a
      method for achieving resolution beyond the classical limit in optical microscopes
      (approx. 200 nm laterally). Yellow fluorescent protein (YFP) has been used for
      super-resolution single molecule localization microscopy, but less frequently
      than other fluorescent probes. Working with YFP in SMLM is a challenge because a
      lower number of photons are emitted per molecule compared with organic dyes,
      which are more commonly used. Publically available experimental data can
      facilitate development of new data analysis algorithms. Findings: Four complete,
      freely available single molecule super-resolution microscopy datasets on YFP
      tagged growth factor receptors expressed in a human cell line are presented,
      including both raw and analyzed data. We report methods for sample preparation,
      for data acquisition, and for data analysis, as well as examples of the acquired
      images. We also analyzed the SMLM datasets using a different method: super
      resolution optical fluctuation imaging (SOFI). The 2 modes of analysis offer
      complementary information about the sample. A fifth single molecule super
      resolution microscopy dataset acquired with the dye Alexa 532 is included for
      comparison purposes. Conclusions: This dataset has potential for extensive reuse.
      Complete raw data from SMLM experiments have typically not been published. The
      YFP data exhibit low signal-to-noise ratios, making data analysis a challenge.
      These datasets will be useful to investigators developing their own algorithms
      for SMLM, SOFI, and related methods. The data will also be useful for researchers
      investigating growth factor receptors such as ErbB3.

PMID- 29361124
TI  - DNA-binding landscape of IRF3, IRF5 and IRF7 dimers: implications for dimer
      specific gene regulation.
AB  - Transcription factors IRF3, IRF5 and IRF7 (IRF3/5/7) have overlapping, yet
      distinct, roles in the mammalian response to pathogens. To examine the role that
      DNA-binding specificity plays in delineating IRF3/5/7-specific gene regulation we
      used protein-binding microarrays (PBMs) to characterize the DNA binding of
      IRF3/5/7 homodimers. We identified both common and dimer-specific DNA binding
      sites, and show that DNA-binding differences can translate into dimer-specific
      gene regulation. Central to the antiviral response, IRF3/5/7 regulate type I
      interferon (IFN) genes. We show that IRF3 and IRF7 bind to many interferon
      stimulated response element (ISRE)-type sites in the virus-response elements
      (VREs) of IFN promoters. However, strikingly, IRF5 does not bind the VREs,
      suggesting evolutionary selection against IRF5 homodimer binding. Mutational
      analysis reveals a critical specificity-determining residue that inhibits IRF5
      binding to the ISRE-variants present in the IFN gene promoters. Integrating PBM
      and reporter gene data we find that both DNA-binding affinity and affinity
      independent mechanisms determine the function of DNA-bound IRF dimers, suggesting
      that DNA-based allostery plays a role in IRF binding site function. Our results
      provide new insights into the role and limitations of DNA-binding affinity in
      delineating IRF3/5/7-specific gene expression.

PMID- 29361125
TI  - Integrative analysis of the late maturation programme and desiccation tolerance
      mechanisms in intermediate coffee seeds.
AB  - The 'intermediate seed' category was defined in the early 1990s using coffee
      (Coffea arabica) as a model. In contrast to orthodox seeds, intermediate seeds
      cannot survive complete drying, which is a major constraint for seed storage and
      has implications for both biodiversity conservation and agricultural purposes.
      However, intermediate seeds are considerably more tolerant to drying than
      recalcitrant seeds, which are highly sensitive to desiccation. To gain insight
      into the mechanisms governing such differences, changes in desiccation tolerance
      (DT), hormone contents, and the transcriptome were analysed in developing coffee
      seeds. Acquisition of DT coincided with a dramatic transcriptional switch
      characterised by the repression of primary metabolism, photosynthesis, and
      respiration, and the up-regulation of genes coding for late-embryogenesis
      abundant (LEA) proteins, heat-shock proteins (HSPs), and antioxidant enzymes.
      Analysis of the heat-stable proteome in mature coffee seeds confirmed the
      accumulation of LEA proteins identified at the transcript level. Transcriptome
      analysis also suggested a major role for ABA and for the transcription factors
      CaHSFA9, CaDREB2G, CaANAC029, CaPLATZ, and CaDOG-like in DT acquisition. The
      ability of CaHSFA9 and CaDREB2G to trigger HSP gene transcription was validated
      by Agrobacterium-mediated transformation of coffee somatic embryos.

PMID- 29361126
TI  - Changes in co-morbidity pattern in patients starting renal replacement therapy in
      Europe-data from the ERA-EDTA Registry.
AB  - Background: Patients starting renal replacement therapy (RRT) for end-stage renal
      disease often present with one or more co-morbidities. This study explored the
      prevalence of co-morbidities in patients who started RRT in Europe during the
      period from 2005 to 2014. Methods: Using data from patients aged 20 years or
      older from all 11 national or regional registries providing co-morbidity data to
      the European Renal Association - European Dialysis and Transplant Association
      Registry, we examined the prevalence of the following co-morbidities: diabetes
      mellitus (DM) (primary renal disease and/or co-morbidity), ischaemic heart
      disease (IHD), congestive heart failure (CHF), peripheral vascular disease (PVD),
      cerebrovascular disease (CVD) and malignancy. Results: Overall, 70% of 7578
      patients who initiated RRT in 2014 presented with at least one co-morbidity:
      39.0% presented with DM, 25.0% with IHD, 22.3% with CHF, 17.7% with PVD, 16.4%
      with malignancy and 15.5% with CVD. These percentages differed substantially
      between countries. Co-morbidities were more common in men than in women, in older
      patients than in younger patients, and in patients on haemodialysis at Day 91
      when compared with patients on peritoneal dialysis. Between 2005 and 2014 the
      prevalence of DM and malignancy increased over time, whereas the prevalence of
      IHD and PVD declined. Conclusions: More than two-thirds of patients initiating
      RRT in Europe have at least one co-morbidity. With the rising age at the start of
      RRT over the last decade, there have been changes in the co-morbidity pattern:
      the prevalence of cardiovascular co-morbidities decreased, while the prevalence
      of DM and malignancy increased.

PMID- 29361127
TI  - Contrasting genetic regulation of plant development in wild barley grown in two
      European environments revealed by nested association mapping.
AB  - Barley is cultivated more widely than the other major world crops because it
      adapts well to environmental constraints, such as drought, heat, and day length.
      To better understand the genetic control of local adaptation in barley, we
      studied development in the nested association mapping population HEB-25, derived
      from crossing 25 wild barley accessions with the cultivar 'Barke'. HEB-25 was
      cultivated in replicated field trials in Dundee (Scotland) and Halle (Germany),
      differing in regard to day length, precipitation, and temperature. Applying a
      genome-wide association study, we located 60 and 66 quantitative trait locus
      (QTL) regions regulating eight plant development traits in Dundee and Halle,
      respectively. A number of QTLs could be explained by known major genes such as
      PHOTOPERIOD 1 (Ppd-H1) and FLOWERING LOCUS T (HvFT-1) that regulate plant
      development. In addition, we observed that developmental traits in HEB-25 were
      partly controlled via genotype * environment and genotype * donor interactions,
      defined as location-specific and family-specific QTL effects. Our findings
      indicate that QTL alleles are available in the wild barley gene pool that show
      contrasting effects on plant development, which may be deployed to improve
      adaptation of cultivated barley to future environmental changes.

PMID- 29361129
TI  - Foraging Distance of the Argentine Ant in California Vineyards.
AB  - Argentine ants, Linepithema humile (Mayr) (Hymenoptera: Formicidae), form
      mutualisms with hemipteran pests in crop systems. In vineyards, they feed on
      honeydew produced by mealybugs and soft scales, which they tend and protect from
      natural enemies. Few options for controlling Argentine ants are available; one of
      the more effective approaches is to use liquid baits containing a low dose of an
      insecticide. Knowledge of ant foraging patterns is required to estimate how many
      bait stations to deploy per unit area. To measure how far ants move liquid bait
      in vineyards, we placed bait stations containing sugar water and a protein marker
      in plots for 6 d, and then collected ants along transects extending away from
      bait stations. The ants moved an average of 16.08 m and 12.21 m from bait
      stations in the first and second years of the study, respectively. Marked ants
      were found up to 63 m from bait stations; however, proportions of marked ants
      decreased exponentially as distance from the bait station increased. Results
      indicate that Argentine ants generally forage at distances <36 m in California
      vineyards, thus suggesting that insecticide bait stations must be deployed at
      intervals of 36 m or less to control ants. We found no effect of insecticide on
      distances that ants moved the liquid bait, but this may have been because bait
      station densities were too low to affect the high numbers of Argentine ants that
      were present at the study sites.

PMID- 29361128
TI  - Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny.
AB  - Simple satellites are tandemly repeating short DNA motifs that can span megabases
      in eukaryotic genomes. Because they can cause genomic instability through
      nonallelic homologous exchange, they are primarily found in the repressive
      heterochromatin near centromeres and telomeres where recombination is minimal,
      and on the Y chromosome, where they accumulate as the chromosome degenerates.
      Interestingly, the types and abundances of simple satellites often vary
      dramatically between closely related species, suggesting that they turn over
      rapidly. However, limited sampling has prevented detailed understanding of their
      evolutionary dynamics. Here, we characterize simple satellites from whole-genome
      sequences generated from males and females of nine Drosophila species, spanning
      40 Ma of evolution. We show that PCR-free library preparation and postsequencing
      GC-correction better capture satellite quantities than conventional methods. We
      find that over half of the 207 simple satellites identified are species-specific,
      consistent with previous descriptions of their rapid evolution. Based on a
      maximum parsimony framework, we determined that most interspecific differences
      are due to lineage-specific gains. Simple satellites gained within a species are
      typically a single mutation away from abundant existing satellites, suggesting
      that they likely emerge from existing satellites, especially in the genomes of
      satellite-rich species. Interestingly, unlike most of the other lineages which
      experience various degrees of gains, the lineage leading up to the satellite-poor
      D. pseudoobscura and D. persimilis appears to be recalcitrant to gains, providing
      a counterpoint to the notion that simple satellites are universally rapidly
      evolving.

PMID- 29361130
TI  - A sigma factor toolbox for orthogonal gene expression in Escherichia coli.
AB  - Synthetic genetic sensors and circuits enable programmable control over timing
      and conditions of gene expression and, as a result, are increasingly incorporated
      into the control of complex and multi-gene pathways. Size and complexity of
      genetic circuits are growing, but stay limited by a shortage of regulatory parts
      that can be used without interference. Therefore, orthogonal expression and
      regulation systems are needed to minimize undesired crosstalk and allow for
      dynamic control of separate modules. This work presents a set of orthogonal
      expression systems for use in Escherichia coli based on heterologous sigma
      factors from Bacillus subtilis that recognize specific promoter sequences. Up to
      four of the analyzed sigma factors can be combined to function orthogonally
      between each other and toward the host. Additionally, the toolbox is expanded by
      creating promoter libraries for three sigma factors without loss of their
      orthogonal nature. As this set covers a wide range of transcription initiation
      frequencies, it enables tuning of multiple outputs of the circuit in response to
      different sensory signals in an orthogonal manner. This sigma factor toolbox
      constitutes an interesting expansion of the synthetic biology toolbox and may
      contribute to the assembly of more complex synthetic genetic systems in the
      future.

PMID- 29361131
TI  - Structural divergence creates new functional features in alphavirus genomes.
AB  - Alphaviruses are mosquito-borne pathogens that cause human diseases ranging from
      debilitating arthritis to lethal encephalitis. Studies with Sindbis virus (SINV),
      which causes fever, rash, and arthralgia in humans, and Venezuelan equine
      encephalitis virus (VEEV), which causes encephalitis, have identified RNA
      structural elements that play key roles in replication and pathogenesis. However,
      a complete genomic structural profile has not been established for these viruses.
      We used the structural probing technique SHAPE-MaP to identify structured
      elements within the SINV and VEEV genomes. Our SHAPE-directed structural models
      recapitulate known RNA structures, while also identifying novel structural
      elements, including a new functional element in the nsP1 region of SINV whose
      disruption causes a defect in infectivity. Although RNA structural elements are
      important for multiple aspects of alphavirus biology, we found the majority of
      RNA structures were not conserved between SINV and VEEV. Our data suggest that
      alphavirus RNA genomes are highly divergent structurally despite similar genomic
      architecture and sequence conservation; still, RNA structural elements are
      critical to the viral life cycle. These findings reframe traditional assumptions
      about RNA structure and evolution: rather than structures being conserved,
      alphaviruses frequently evolve new structures that may shape interactions with
      host immune systems or co-evolve with viral proteins.

PMID- 29361133
TI  - Comparison of physical and biological properties of CardioCel(r) with commonly
      used bioscaffolds.
AB  - OBJECTIVES: Durability of bioscaffolds cross-linked with glutaraldehyde and used
      in cardiovascular surgery is limited by biomechanical instability, calcification
      and reduced biocompatibility. This study compares CardioCel(r), a bovine
      pericardial scaffold engineered via the ADAPT(r) process to ensure optimized
      biostability and biocompatibility, with the commonly used bioscaffolds. METHODS:
      Bovine pericardial scaffolds, cross-linked with 0.6% glutaraldehyde (XenoLogiXTM,
      PeriGuard(r)), dye-mediated photo-oxidized (PhotoFixTM) and a non-crosslinked
      porcine scaffold (CorMatrix(r)), were compared with CardioCel (decellularized,
      cross-linked with 0.05% monomeric glutaraldehyde, detoxified) by thermal
      stability and mechanical tests. Biocompatibility and calcification were assessed
      in a juvenile subcutaneous rat model at 6 and 12 weeks. RESULTS: CardioCel
      displayed significantly higher (P < 0.01) cross-link stability (77.99 +/- 0.64 
      degrees C) than CorMatrix (57.88 +/- 0.22  degrees C) and PhotoFix (53.96 +/-
      0.41  degrees C). Tensile strength of CardioCel (8.31 +/- 3.36 MPa) was
      comparable with XenoLogiX (11.00 +/- 5.43 MPa, P = 0.734), PeriGuard (16.44 +/-
      6.69 MPa, P = 0.136), PhotoFix (7.10 +/- 6.11, P = 0.399) and CorMatrix (9.75 +/-
      2.61, P = 0.204). XenoLogiX and PeriGuard recorded the highest Young's modulus
      (67.01 +/- 30.36 vs 95.67 +/- 45.91 MPa), while CardioCel (50.21 +/- 19.92 MPa)
      was comparable with CorMatrix (36.78 +/- 10.47 MPa, P = 0.204) and PhotoFix
      (33.50 +/- 10.24, P = 0.399). CorMatrix displayed a significantly (P < 0.05)
      greater stiffness (4.74 +/- 0.77 MPa) at 10% strain than PeriGuard (3.73 +/- 1.79
      MPa), PhotoFix (1.59 +/- 0.40 MPa) and CardioCel (3.39 +/- 0.83 MPa). Differences
      in extractable calcium did not reach significance; however, the inorganic
      phosphorus content of PhotoFix (21.3 +/- 9.0 ug/mg) was higher than CardioCel
      (11.35 +/- 0.76 ug/mg, P = 0.004) or PeriGuard (10.7 +/- 2.18 ug/mg, P = 0.002)
      at 12 weeks. CardioCel underwent a typical mild host-graft response with
      fibroblast infiltration and remodelling. Foreign body reactions were visible in
      both XenoLogiX and PeriGuard, with isolated fibroblast infiltration. PhotoFix
      showed severe inflammation and 2 implants were completely degraded at 12 weeks.
      CONCLUSIONS: CardioCel demonstrated optimized physical properties, minimal
      mineralization potential and superior biocompatibility. These results may benefit
      the long-term performance of this bioscaffold for cardiovascular surgery. The
      favourable characteristics of the comparator products were counterbalanced by
      less desirable features that may have negative implications on durability and
      performance when used in cardiovascular procedures.

PMID- 29361132
TI  - Characterization of DNA ADP-ribosyltransferase activities of PARP2 and PARP3: new
      insights into DNA ADP-ribosylation.
AB  - Poly(ADP-ribose) polymerases (PARPs) act as DNA break sensors and catalyze the
      synthesis of polymers of ADP-ribose (PAR) covalently attached to acceptor
      proteins at DNA damage sites. It has been demonstrated that both mammalian PARP1
      and PARP2 PARylate double-strand break termini in DNA oligonucleotide duplexes in
      vitro. Here, we show that mammalian PARP2 and PARP3 can PARylate and mono(ADP
      ribosyl)ate (MARylate), respectively, 5'- and 3'-terminal phosphate residues at
      double- and single-strand break termini of a DNA molecule containing multiple
      strand breaks. PARP3-catalyzed DNA MARylation can be considered a new type of
      reversible post-replicative DNA modification. According to DNA substrate
      specificity of PARP3 and PARP2, we propose a putative mechanistic model of PARP
      catalyzed strand break-oriented ADP-ribosylation of DNA termini. Notably, PARP
      mediated DNA ADP-ribosylation can be more effective than PARPs' auto-ADP
      ribosylation depending on the DNA substrates and reaction conditions used.
      Finally, we show an effective PARP3- or PARP2-catalyzed ADP-ribosylation of high
      molecular-weight (~3-kb) DNA molecules, PARP-mediated DNA PARylation in cell-free
      extracts and a persisting signal of anti-PAR antibodies in a serially purified
      genomic DNA from bleomycin-treated poly(ADP-ribose) glycohydrolase-depleted HeLa
      cells. These results suggest that certain types of complex DNA breaks can be
      effectively ADP-ribosylated by PARPs in cellular response to DNA damage.

PMID- 29361134
TI  - Investigating the feasibility of tumour molecular profiling in gastrointestinal
      malignancies in routine clinical practice.
AB  - Background: Targeted capture sequencing can potentially facilitate precision
      medicine, but the feasibility of this approach in gastrointestinal (GI)
      malignancies is unknown. Patients and methods: The FOrMAT (Feasibility of a
      Molecular Characterisation Approach to Treatment) study was a feasibility study
      enrolling patients with advanced GI malignancies from February 2014 to November
      2015. Targeted capture sequencing (mainly using archival formalin-fixed paraffin
      embedded diagnostic/resection samples) was carried out to detect mutations, copy
      number variations and translocations in up to 46 genes which had
      prognostic/predictive significance or were targets in current/upcoming clinical
      trials. Results: Of the 222 patients recruited, 215 patients (96.8%) had
      available tissue samples, 125 patients (56.3%) had >=16 genes successfully
      sequenced and 136 patients (61.2%) had >=1 genes successfully sequenced. Sample
      characteristics influenced the proportion of successfully sequenced samples, e.g.
      tumour type (colorectal 70.9%, biliary 52.6%, oesophagogastric 50.7%, pancreas
      27.3%, P = 0.002), tumour cellularity (high versus low: 78.3% versus 13.3%, P <=
      0.001), tumour content (high versus low: 78.6% versus 27.3%, P = 0.001) and type
      of sample (resection versus biopsy: 82.4% versus 47.6%, P <= 0.001). Currently,
      actionable alterations were detected in 90 (40.5%) of the 222 patients recruited
      (66% of the 136 patients sequenced) and 2 patients subsequently received a
      targeted therapy. The most frequently detected currently actionable alterations
      were mutations in KRAS, BRAF, TP53 and PIK3CA. For the 205 patients with archival
      samples, the median time to obtain sequencing results was 18.9 weeks, including a
      median of 4.9 weeks for sample retrieval and 5.1 weeks for sequencing.
      Conclusions: Targeted sequencing detected actionable alterations in formalin
      fixed paraffin-embedded samples, but tissue characteristics are of critical
      importance in determining sequencing success. Routine molecular profiling of GI
      tumours outside of clinical trials is not an effective use of healthcare
      resources unless more targeted drugs become available. ClinicalTrials.gov
      identifier: NCT02112357.

PMID- 29361135
TI  - Detection of PD-L1 in circulating tumor cells and white blood cells from patients
      with advanced non-small-cell lung cancer.
AB  - Background: Expression of PD-L1 in tumor cells and tumor-infiltrating immune
      cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in
      patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a
      potential biomarker for the selection of patients to cancer immunotherapies. We
      investigated the utility of circulating tumor cells (CTCs) and circulating white
      blood cells (WBCs) as a noninvasive method to evaluate PD-L1 status in advanced
      NSCLC patients. Patients and methods: CTCs and circulating WBCs were enriched
      from peripheral blood samples (ISET(r) platform; Rarecells) from 106 NSCLC
      patients. PD-L1 expression on ISET filters and matched-tumor tissue was evaluated
      by automated immunostaining (SP142 antibody; Ventana), and quantified in tumor
      cells and WBCs. Results: CTCs were detected in 80 (75%) patients, with levels
      ranging from 2 to 256 CTCs/4 ml, and median of 60 CTCs/4 ml. Among 71 evaluable
      samples with matched-tissue and CTCs, 6 patients (8%) showed >=1 PD-L1-positive
      CTCs and 11 patients (15%) showed >=1% PD-L1-positive tumor cells in tumor tissue
      with 93% concordance between tissue and CTCs (sensitivity = 55%; specificity =
      100%). From 74 samples with matched-tissue and circulating WBCs, 40 patients
      (54%) showed >=1% PD-L1-positive immune infiltrates in tumor tissue and 39
      patients (53%) showed >=1% PD-L1 positive in circulating WBCs, with 80%
      concordance between blood and tissue (sensitivity = 82%; specificity = 79%). We
      found a trend for worse survival in patients receiving first-line cisplatin-based
      chemotherapy treatments, whose tumors express PD-L1 in CTCs or immune cells
      (progression-free and overall survival), similar to the effects of PD-L1
      expression in matched-patient tumors. Conclusions: These results demonstrated
      that PD-L1 status in CTCs and circulating WBCs correlate with PD-L1 status in
      tumor tissue, revealing the potential of CTCs assessment as a noninvasive real
      time biopsy to evaluate PD-L1 expression in patients with advanced-stage NSCLC.

PMID- 29361136
TI  - Differential binding affinity of mutated peptides for MHC class I is a predictor
      of survival in advanced lung cancer and melanoma.
AB  - Background: Cancer mutations generate novel (neo-)peptides recognised by T cells,
      but the determinants of recognition are not well characterised. The difference in
      predicted class I major histocompatibility complex (MHC-I) binding affinity
      between wild-type and corresponding mutant peptides (differential agretopicity
      index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our
      aim was to explore the relationship between DAI, measures of immune infiltration
      and patient outcomes in advanced cancer. Patients and methods: Cohorts of
      patients with advanced non-small-cell lung cancer (NSCLC; LUAD, n = 66) and
      melanoma (SKCM, n = 72) were obtained from The Cancer Genome Atlas. Three
      additional cohorts of immunotherapy treated patients with advanced melanoma
      (total n = 131) and NSCLC (n = 31) were analysed. Neopeptides and their clonal
      status were defined using genomic data. MHC-I binding affinity was predicted for
      each neopeptide and DAI values summarised as the sample mean DAI. Correlations
      between mean DAI and markers of immune activity were evaluated using measures of
      lymphocyte infiltration and immune gene expression. Results: In univariate and
      multivariate analyses, mean DAI significantly correlated with overall survival in
      3/5 cohorts, with evidence of superiority over nonsynonymous mutational and
      neoantigen burden. In these cohorts, the effect was seen for mean DAI of clonal
      but not subclonal peptides. In SKCM, the association between mean DAI and
      survival bordered significance (P = 0.068), reaching significance in an
      immunotherapy-treated melanoma cohort (P = 0.003). Mean DAI but not mutational
      nor neoantigen burden was positively correlated with independently derived
      markers of immune infiltration in both SKCM (P = 0.027) and LUAD (P = 0.024).
      Conclusions: The association between mean DAI, survival and measures of immune
      activity support the hypothesis that DAI is a determinant of cancer peptide
      immunogenicity. Investigation of DAI as a marker of immunologically relevant
      peptides in further datasets and future clinical studies of neoantigen based
      immunotherapies is warranted.

PMID- 29361137
TI  - Homodimer formation by the ATP/UTP receptor P2Y2 via disulfide bridges.
AB  - Many class C G-protein coupled receptors (GPCRs) function as homo- or
      heterodimers and several class A GPCRs have also been shown to form a homodimer.
      We expressed human P2Y2 receptor (P2Y2R) in cultured cells and compared SDS-PAGE
      patterns under reducing and non-reducing conditions. Under non-reducing
      conditions, approximately half of the P2Y2Rs were electrophoresed as a dimer. We
      then produced Cys to Ser mutants at four sites (Cys25, Cys106, Cys183 and Cys278)
      in the extracellular domains of P2Y2R and examined the effect on dimer formation
      and receptor activity. All single mutants formed dimers similarly to the wild
      type protein, but C25S, C106S and C183S P2Y2R lost activity, while C278S P2Y2R
      maintained weak activity. Coexpression with wild-type P2Y2R recovered the
      activity of the C25S mutant. These results show that Cys106 and Cys183 are
      required for monomer or homodimer activity; Cys25 is required for monomer
      activity, but it is not needed in one protomer for homodimer activity; and Cys278
      can be replaced in the monomer and homodimer. Approximately, half of C25S/C278S
      double mutants were electrophoresed as a dimer, similarly to the wild-type and
      single mutants, and dimers with the wild-type protein were active. These results
      suggest involvement of Cys106 and Cys183 in disulfide bonding between protomers
      in homodimer formation.

PMID- 29361138
TI  - The WOX11-LBD16 Pathway Promotes Pluripotency Acquisition in Callus Cells During
      De Novo Shoot Regeneration in Tissue Culture.
AB  - De novo shoot regeneration in tissue culture undergoes at least two phases.
      Explants are first cultured on auxin-rich callus-inducing medium (CIM) to produce
      a group of pluripotent cells termed callus; the callus is then transferred to
      cytokinin rich shoot-inducing medium (SIM) to promote the formation of shoot
      progenitor cells, from which adventitious shoots may differentiate. Here, we show
      that the Arabidopsis thaliana transcription factor gene LATERAL ORGAN BOUNDARIES
      DOMAIN16 (LBD16) is involved in pluripotency acquisition in callus cells. LBD16,
      which is activated by WUSCHEL RELATED HOMEOBOX11 (WOX11), is specifically
      expressed in the newly formed callus on CIM and its expression decreases quickly
      when callus is moved to SIM. Blocking the WOX11-LBD16 pathway results in the loss
      of pluripotency in callus cultured on CIM, leading to shooting defects on SIM.
      Further analysis showed that LBD16 may function in the establishment of the root
      primordium-like identity in the newly formed callus, indicating that the root
      primordium-like identity is the cellular nature of pluripotency in callus cells.
      Additionally, LBD16 promotes cell division during callus initiation. Our study
      clarified that the WOX11-LBD16 pathway promotes pluripotency acquisition in
      callus cells.

PMID- 29361140
TI  - A rapid fluorescent indicator displacement assay and principal component/cluster
      data analysis for determination of ligand-nucleic acid structural selectivity.
AB  - We describe a rapid fluorescence indicator displacement assay (R-FID) to evaluate
      the affinity and the selectivity of compounds binding to different DNA
      structures. We validated the assay using a library of 30 well-known nucleic acid
      binders containing a variety chemical scaffolds. We used a combination of
      principal component analysis and hierarchical clustering analysis to interpret
      the results obtained. This analysis classified compounds based on selectivity for
      AT-rich, GC-rich and G4 structures. We used the FID assay as a secondary screen
      to test the binding selectivity of an additional 20 compounds selected from the
      NCI Diversity Set III library that were identified as G4 binders using a thermal
      shift assay. The results showed G4 binding selectivity for only a few of the 20
      compounds. Overall, we show that this R-FID assay, coupled with PCA and HCA,
      provides a useful tool for the discovery of ligands selective for particular
      nucleic acid structures.

PMID- 29361139
TI  - Diff-seq: A high throughput sequencing-based mismatch detection assay for DNA
      variant enrichment and discovery.
AB  - Much of the within species genetic variation is in the form of single nucleotide
      polymorphisms (SNPs), typically detected by whole genome sequencing (WGS) or
      microarray-based technologies. However, WGS produces mostly uninformative reads
      that perfectly match the reference, while microarrays require genome-specific
      reagents. We have developed Diff-seq, a sequencing-based mismatch detection assay
      for SNP discovery without the requirement for specialized nucleic-acid reagents.
      Diff-seq leverages the Surveyor endonuclease to cleave mismatched DNA molecules
      that are generated after cross-annealing of a complex pool of DNA fragments.
      Sequencing libraries enriched for Surveyor-cleaved molecules result in increased
      coverage at the variant sites. Diff-seq detected all mismatches present in an
      initial test substrate, with specific enrichment dependent on the identity and
      context of the variation. Application to viral sequences resulted in increased
      observation of variant alleles in a biologically relevant context. Diff-Seq has
      the potential to increase the sensitivity and efficiency of high-throughput
      sequencing in the detection of variation.

PMID- 29361141
TI  - Vacuolar Transporters for Cadmium and Arsenic in Plants and their Applications in
      Phytoremediation and Crop Development.
AB  - Soil contamination by heavy metals and metalloids such as cadmium (Cd) and
      arsenic (As) poses a major threat to the environment and to human health.
      Vacuolar sequestration is one of the main mechanisms by which plants control
      toxic materials including Cd and As. Understanding the mechanisms of heavy metal
      tolerance and accumulation can be useful for both phytoremediation and safe crop
      development. In this review, we summarize recent advances in deciphering the
      molecular mechanisms underlying vacuolar sequestration of Cd and As, and discuss
      potential biotechnological applications of this knowledge and efforts towards
      attaining these goals.

PMID- 29361142
TI  - Multiple target autoantigens on endothelial cells identified in juvenile
      dermatomyositis using proteomics.
AB  - Objective: Although generally classified within the group of inflammatory
      myopathies, JDM displays many pathological features of vasculitis. Previous work
      has shown that AECA are abundant in other forms of vasculitis. We therefore
      investigated whether such antibodies might also be detected in JDM. Methods: We
      screened plasma from children with JDM for the presence of AECA by western
      blotting and 2D gel electrophoresis (2DE) using proteins extracted from human
      aortic endothelial cells as the substrate. We performed mass spectrometry to
      identify candidate antigens from 2DE gels and used ELISA to confirm the presence
      of specific antibodies. Results: We identified 22 candidate target autoantigens
      for AECA probed with JDM plasma. Interestingly, 17 of these 22 target antigens
      were proteins associated with antigen processing and protein trafficking. ELISA
      confirmed the presence of antibodies to heat shock cognate 71 kDa protein in JDM
      plasma, particularly in children with active, untreated disease. Conclusion:
      Children with JDM express antibodies to autoantigens in endothelial cells. The
      clinical and pathological significance of such autoantibodies require further
      investigation.

PMID- 29361143
TI  - Epididymal cysteine-rich secretory proteins are required for epididymal sperm
      maturation and optimal sperm function.
AB  - STUDY QUESTION: What is the role of epididymal cysteine-rich secretory proteins
      (CRISPs) in male fertility? SUMMARY ANSWER: While epididymal CRISPs are not
      absolutely required for male fertility, they are required for optimal sperm
      function. WHAT IS KNOWN ALREADY: CRISPs are members of the CRISP, Antigen 5 and
      Pathogenesis related protein 1 (CAP) superfamily and are characterized by the
      presence of an N-terminal CAP domain and a C-terminal CRISP domain. CRISPs are
      highly enriched in the male reproductive tract of mammals, including in the
      epididymis. Within humans there is one epididymal CRISP, CRISP1, whereas in mice
      there are two, CRISP1 and CRISP4. STUDY DESIGN, SIZE, DURATION: In order to
      define the role of CRISPs within the epididymis, Crisp1 and Crisp4 knockout mouse
      lines were produced then interbred to produce Crisp1 and 4 double knockout (DKO)
      mice, wherein the expression of all epididymal CRISPs was ablated. Individual and
      DKO models were then assessed, relative to their own strain-specific wild type
      littermates for fertility, and sperm output and functional competence at young
      (10-12 weeks of age) and older ages (22-24 weeks). Crisp1 and 4 DKO and control
      mice were also compared for their ability to bind to the zona pellucida and
      achieve fertilization. PARTICIPANTS/MATERIALS, SETTING, METHODS: Knockout mouse
      production was achieved using modified embryonic stem cells and standard methods.
      The knockout of individual genes was confirmed at a mRNA (quantitative PCR) and
      protein (immunochemistry) level. Fertility was assessed using breeding
      experiments and a histological assessment of testes and epididymal tissue. Sperm
      functional competence was assessed using a computer assisted sperm analyser,
      induction of the acrosome reaction using progesterone followed by staining for
      acrosome contents, using immunochemical and western blotting to assess the
      ability of sperm to manifest tyrosine phosphorylation under capacitating
      conditions and using sperm-zona pellucida binding assays and IVF methods. A
      minimum of three biological replicates were used per assay and per genotype. MAIN
      RESULTS AND THE ROLE OF CHANCE: While epididymal CRISPs are not absolutely
      required for male fertility, their production results in enhanced sperm function
      and, depending on context, CRISP1 and CRISP4 act redundantly or autonomously.
      Specifically, CRISP1 is the most important CRISP in the establishment of normally
      motile sperm, whereas CRISP4 acts to enhance capacitation-associated tyrosine
      phosphorylation, and CRISP1 and CRISP4 act together to establish normal acrosome
      function. Both are required to achieve optimal sperm-egg interaction. The
      presence of immune infiltrates into the epididymis of older, but not younger, DKO
      animals also suggests epididymal CRISPs function to produce an immune privileged
      environment for maturing sperm within the epididymis. LIMITATIONS REASONS FOR
      CAUTION: Caution should be displayed in the translation of mouse-derived data
      into the human wherein the histology of the epididymis is someone what different.
      The mice used in the study were housed in a specific pathogen-free environment
      and were thus not exposed to the full range of environmental challenges
      experienced by wild mice or humans. As such, the role of CRISPs in the
      maintenance of an immune privileged environment, for example, may be understated.
      WIDER IMPLICATIONS OF THE FINDINGS: The combined deletion of Crisp1 and Crisp4 in
      mice is equivalent to the removal of all CRISP expression in humans. As such,
      these data suggest that mammalian CRISPs, including that in humans, function to
      enhance sperm function and thus male fertility. These data also suggest that in
      the presence of an environmental challenge, CRISPs help to maintain an immune
      privileged environment and thus, protect against immune-mediated male
      infertility. LARGE SCALE DATA: Not applicable. STUDY FUNDING AND COMPETING
      INTEREST(S): This study was funded by the National Health and Medical Research
      Council, the Victorian Cancer Agency and a scholarship from the Chinese
      Scholarship Council. The authors have no conflicts of interest to declare.

PMID- 29361144
TI  - High calcium to phosphorus ratio impairs growth and bone mineralization in Pekin
      ducklings.
AB  - Two experiments were conducted to investigate the effect of high dietary calcium
      (Ca) level on growth performance, Ca and phosphorus (P) metabolism, and nutrient
      utilization in ducklings subjected to normal and low P levels in diets. A
      completely randomized design was used with a factorial arrangement of 2 total
      dietary P levels [normal-P (0.60%) and low-P (0.45%) groups] * 4 dietary Ca
      levels [low-Ca (0.55%), normal-Ca (0.75%), medium-Ca (0.95%) and high-Ca (1.15%)
      groups)]. Compared to normal-P group, low-P group had lower (P < 0.05) final body
      weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) and
      reduced (P < 0.05) serum Ca and P levels, bone Ca, P, and ash content, and bone
      mineral density in ducklings during the starter period. Under the low-P group,
      birds from high-Ca group had lower (P < 0.05) final BW, ADG, ADFI, bone ash
      content, bone mineral density, and the utilization of energy, Ca, and P than
      those from low-Ca, normal-Ca, and medium-Ca groups. Our results indicate that
      high-Ca diet induced greater growth suppression and bone mineralization loss in
      ducklings fed a low-P diet. The aggravated negative effect of high dietary Ca
      level with a low P level might be related to the elevated serum alkaline
      phosphatase activity and the reduced utilization of energy, Ca, and P.

PMID- 29361145
TI  - Adding a new dimension to the weekend effect: an analysis of a national data set
      of electronic AKI alerts.
AB  - Background: Increased mortality related to differences in delivery of weekend
      clinical care is the subject of much debate. Aim: We compared mortality following
      detection of acute kidney injury (AKI) on week and weekend days across community
      and hospital settings. Design: A prospective national cohort study, with AKI
      identified using the Welsh National electronic AKI reporting system. Methods:
      Data were collected on outcome for all cases of adult AKI in Wales between 1
      November 2013 and 31 January 2017. Results: There were a total of 107 298
      episodes. Weekday detection of AKI was associated with 28.8% (26 439); 90-day
      mortality compared to 90-day mortality of 31.9% (4551) for AKI detected on
      weekdays (RR: 1.11, 95% CI: 1.08-1.14, P < 0.001, HR: 1.16 95% CI: 1.12-1.20, P <
      0.001). There was no 'weekend effect' for mortality associated with hospital
      acquired AKI. Weekday detection of community-acquired AKI (CA-AKI) was associated
      with a 22.6% (10 356) mortality compared with weekend detection of CA-AKI, which
      was associated with a 28.6% (1619) mortality (RR: 1.26, 95% CI: 1.21-1.32, P <
      0.001, HR: 1.34, 95%CI: 1.28-1.42, P < 0.001). The excess mortality in weekend CA
      AKI was driven by CA-AKI detected at the weekend that was not admitted to
      hospital compared with CA-AKI detected on weekdays which was admitted to hospital
      (34.5% vs. 19.1%, RR: 1.8, 95% CI: 1.69-1.91, P < 0.001, HR: 2.03, 95% CI: 1.88
      2.19, P < 0.001). Conclusion: 'Weekend effect' in AKI relates to access to in
      patient care for patients presenting predominantly to hospital emergency
      departments with AKI at the weekend.

PMID- 29361146
TI  - Plasma levels of hsa-miR-152-3p are associated with diabetic nephropathy in
      patients with type 2 diabetes.
AB  - Background: MicroRNAs (miRNAs) are small non-coding RNAs participating in post
      transcriptional regulation of genes. Their key role in modulating the
      susceptibility to human diseases is now widely recognized, in particular in the
      context of cardiometabolic disorders. The aim of the present study was to
      identify miRNAs associated with diabetic nephropathy (DN) in patients with type 2
      diabetes (T2D). Methods: A next-generation sequencing-based miRNA profiling was
      performed in a case-control study for DN in plasma samples of 23 T2D patients
      with DN (cases) and 23 T2D without (controls). The main associations were
      confirmed using quantitative reverse transcription-polymerase chain reaction and
      tested for replication in an independent case-control collection of 100 T2D
      patients, 50 with DN and 50 without. Results: From the 381 known mature miRNAs
      that were found highly expressed in the discovery samples, we observed and
      replicated an association between increased plasma levels of hsa-miR-152-3p and
      DN (P = 4.03 * 10-4 in the combined samples). Hsa-miR-152-3p plasma levels were
      further found to be positively correlated (P = 0.003) to plasma osmolarity, a
      surrogate marker for solute carrier net activity, whose regulation is controlled
      by several genes including SLC5A3, one of the predicted targets of hsa-miR-152
      3p. Conclusions: We observed strong evidence for the association of hsa-miR-152
      3p plasma levels and DN in patients with T2D, confirming an association
      previously observed in patients with type 1 diabetes.

PMID- 29361148
TI  - A New Species of Simulium (Asiosimulium) (Diptera: Simuliidae) from Thailand.
AB  - Simulium (Asiosimulium) saeungae sp. nov. (Diptera: Simuliidae) is described
      based on females, males, pupae, and mature larvae collected from Nan Province,
      Northern Thailand. It is characterized by the medium-long cerci in the female,
      enlarged hind basitarsus, and broad ventral plate with its posterior margin not
      deeply concave in the male, arborescent pupal gill with 42-56 filaments in the
      pupa and smaller number of primary rays of the labral fan (30-33) in the larva.
      This is the fifth species of the subgenus Asiosimulium, the second smallest among
      10 subgenera in the Oriental Region. Taxonomic notes are given to distinguish
      this new species from the three known species from Thailand and one from Nepal.

PMID- 29361147
TI  - Glucocorticoid use and factors associated with variability in this use in the
      Systemic Lupus International Collaborating Clinics Inception Cohort.
AB  - Objectives: To describe glucocorticoid (GC) use in the SLICC inception cohort and
      to explore factors associated with GC use. In particular we aimed to assess
      temporal trends in GC use and to what extent physician-related factors may
      influence use. Methods: Patients were recruited within 15 months of diagnosis of
      SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually.
      Descriptive statistics were used to detail oral and parenteral GC use. Cross
      sectional and longitudinal analyses were performed to explore factors associated
      with GC use at enrolment and over time. Results: We studied 1700 patients with a
      mean (s.d.) follow-up duration of 7.26 (3.82) years. Over the entire study
      period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received
      parenteral GCs at some point. GC use was strongly associated with treatment
      centre, age, race/ethnicity, sex, disease duration and disease activity. There
      was no change in the proportion of patients on GCs or the average doses of GC
      used over time according to year of diagnosis. Conclusion: GCs remain a
      cornerstone in SLE management and there have been no significant changes in their
      use over the past 10-15 years. While patient and disease factors contribute to
      the variation in GC use, between-centre differences suggest that physician
      related factors also contribute. Evidence-based treatment algorithms are needed
      to inform a more standardized approach to GC use in SLE.

PMID- 29361150
TI  - National scale-up of tuberculosis-human immunodeficiency virus collaborative
      activities in Myanmar from 2005 to 2016 and tuberculosis treatment outcomes for
      patients with human immunodeficiency virus-positive tuberculosis in the Mandalay
      Region in 2015.
AB  - Background: HIV-associated TB is a serious public health problem in Myanmar.
      Study objectives were to describe national scale-up of collaborative activities
      to reduce the double burden of TB and HIV from 2005 to 2016 and to describe TB
      treatment outcomes of individuals registered with HIV-associated TB in 2015 in
      the Mandalay Region. Methods: Secondary analysis of national aggregate data and,
      for treatment outcomes, a cohort study of patients with HIV-associated TB in the
      Mandalay Region. Results: The number of townships implementing collaborative
      activities increased from 7 to 330 by 2016. The number of registered TB patients
      increased from 1577 to 139 625 in 2016, with the number of individuals tested for
      HIV increasing from 432 to 114 180 (82%) in 2016: 10 971 (10%) were diagnosed as
      HIV positive. Uptake of co-trimoxazole preventive therapy (CPT) and
      antiretroviral therapy (ART) nationally in 2016 was 77% and 52%, respectively. In
      the Mandalay Region, treatment success was 77% and mortality was 18% in 815 HIV
      associated TB patients. Risk factors for unfavourable outcomes and death were
      older age (>=45 years) and not taking CPT and/or ART. Conclusion: Myanmar is
      making good progress with reducing the HIV burden in TB patients, but better
      implementation is needed to reach 100% HIV testing and 100% CPT and ART uptake in
      TB-HIV co-infected patients.

PMID- 29361149
TI  - Scopoletin 8-hydroxylase: a novel enzyme involved in coumarin biosynthesis and
      iron-deficiency responses in Arabidopsis.
AB  - Iron deficiency is a serious agricultural problem, particularly in alkaline
      soils. Secretion of coumarins by Arabidopsis thaliana roots is induced under iron
      deficiency. An essential enzyme for the biosynthesis of the major Arabidopsis
      coumarins, scopoletin and its derivatives, is Feruloyl-CoA 6'-Hydroxylase1
      (F6'H1), which belongs to a large enzyme family of the 2-oxoglutarate and Fe2+
      dependent dioxygenases. We have functionally characterized another enzyme of this
      family, which is a close homologue of F6'H1 and is encoded by a strongly iron
      responsive gene, At3g12900. We purified At3g12900 protein heterologously
      expressed in Escherichia coli and demonstrated that it is involved in the
      conversion of scopoletin into fraxetin, via hydroxylation at the C8 position, and
      that it thus functions as a scopoletin 8-hydroxylase (S8H). Its function in plant
      cells was confirmed by the transient expression of S8H protein in Nicotiana
      benthamiana leaves, followed by metabolite profiling and biochemical and ionomic
      characterization of Arabidopsis s8h knockout lines grown under various iron
      regimes. Our results indicate that S8H is involved in coumarin biosynthesis, as
      part of mechanisms used by plants to assimilate iron.

PMID- 29361151
TI  - Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the
      modulation of gut microbiota and SFRP2 demethylation.
AB  - Freeze-dried black raspberry (BRB) powder is considered as a potential cancer
      chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium
      sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for
      12 weeks, and this led to a reduction in colon carcinogenesis. These animals had
      consistently lower tumor multiplicity compared with AOM/DSS-treated mice not
      receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic
      bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased
      significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium
      prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins
      supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also
      caused the demethylation of the SFRP2 gene promoter, resulting in increased
      expression of SFRP2, both at the mRNA and protein levels. Furthermore, the
      expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated
      by BRB anthocyanins in these animals. Taken together, these results suggested
      that BRB anthocyanins could modulate the composition of gut commensal microbiota,
      and changes in inflammation and the methylation status of the SFRP2 gene may play
      a central role in the chemoprevention of CRC.

PMID- 29361152
TI  - Sequanix: a dynamic graphical interface for Snakemake workflows.
AB  - Summary: We designed a PyQt graphical user interface-Sequanix-aimed at
      democratizing the use of Snakemake pipelines in the NGS space and beyond. By
      default, Sequanix includes Sequana NGS pipelines (Snakemake format)
      (http://sequana.readthedocs.io), and is also capable of loading any external
      Snakemake pipeline. New users can easily, visually, edit configuration files of
      expert-validated pipelines and can interactively execute these production-ready
      workflows. Sequanix will be useful to both Snakemake developers in exposing their
      pipelines and to a wide audience of users. Availability and implementation:
      Source on http://github.com/sequana/sequana, bio-containers on
      http://bioconda.github.io and Singularity hub (http://singularity-hub.org).
      Contact: dimitri.desvillechabrol@pasteur.fr or thomas.cokelaer@pasteur.fr.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29361153
TI  - Physician Judgments and the Burden of Chronic Pain.
AB  - Objective: In a moderated mediation model, this study examined the interaction
      effect of pain severity and medical evidence on physician judgments of chronic
      pain. The effects of higher pain severity on physician judgments were expected to
      be mediated through anticipated clinical burden, but only when medical evidence
      was low. Design: Participants were randomly assigned to one of six case
      descriptions of a chronic pain patient in a 3 * 2 design that varied by reported
      pain severity (4, 6, 8/10) and medical evidence (low vs high). Setting: An
      academic training program for medical residents/fellows. Subjects:
      Residents/fellows in clinical departments at postgraduate year 2 or higher (N =
      109). Methods: Participants read case descriptions and then made judgments about
      the patient and rated the level of burden they expected to assume in treating the
      patient. Results: Higher pain severity occasioned greater pain discounting and
      higher likelihood of prescribing opioid medication. When medical evidence was
      low, participants had less trust in the patient's pain report, attributed pain
      more to psychosocial than medical factors, and were less likely to refer for
      possible surgery. Analyses yielded no support for moderated mediation as expected
      burden was high across all conditions. Significant associations were found
      between expected burden and multiple clinical judgments. Conclusions: Results did
      not support the proposed moderated mediation model as all patients were expected
      to be burdensome across clinical presentations, reflecting negative expectations
      of patients with chronic pain. Such expectations can have adverse implications
      for patient-provider communication, shared decision-making, and the delivery of
      personalized care.

PMID- 29361154
TI  - Bone remodelling: locus minori or unappreciated potential of tofacitinib?

PMID- 29361155
TI  - Reliability of simple capillaroscopic definitions in describing capillary
      morphology in rheumatic diseases.

PMID- 29361156
TI  - DEVELOPING RADIATION RESISTANT THERMAL NEUTRON DETECTORS FOR THE E_LIBANS
      PROJECT: PRELIMINARY RESULTS.
AB  - Radiation-resistant, gamma-insensitive, active thermal neutron detectors were
      developed to monitor the thermal neutron cavity of the E_LIBANS project. Silicon
      and silicon carbide semiconductors, plus vented air ion chambers, were chosen for
      this purpose. This communication describes the performance of these detectors,
      owing on the results of dedicated measurement campaigns.

PMID- 29361158
TI  - Evaluation of Caenorhabditis elegans as a host model for Paracoccidioides
      brasiliensis and Paracoccidioides lutzii.
AB  - Paracoccidioidomycosis is a systemic fungal infection affecting mainly Latin
      American countries that is caused by Paracoccidioides brasiliensis and
      Paracoccidioides lutzii. During the study of fungal pathogenesis, in vivo studies
      are crucial to understand the overall mechanisms involving the infection as well
      as to search for new therapeutic treatments and diagnosis. Caenorhabditis elegans
      is described as an infection model for different fungi species and a well
      characterized organism to study the innate immune response. This study evaluates
      C. elegans as an infection model for Paracoccidioides spp. It was observed that
      both species do not cause infection in C. elegans, as occurs with Candida
      albicans, and one possible explanation is that the irregular size and shape of
      Paracoccidioides spp. difficult the ingestion of these fungi by the nematode.
      Besides this difficulty in the infection, we could observe that the simple
      exposition of C. elegans to Paracoccidioides species was able to trigger a
      distinct pattern of expression of antimicrobial peptide genes. The expression of
      cnc-4, nlpl-27 and nlp-31 was superior after the exposure to P. brasiliensis in
      comparison to P. lutzii (P < 0.05), and these findings demonstrate important
      differences regarding innate immune response activation caused by the two species
      of the Paracoccidioides genus.

PMID- 29361157
TI  - APE2 promotes DNA damage response pathway from a single-strand break.
AB  - As the most common type of DNA damage, DNA single-strand breaks (SSBs) are
      primarily repaired by the SSB repair mechanism. If not repaired properly or
      promptly, unrepaired SSBs lead to genome stability and have been implicated in
      cancer and neurodegenerative diseases. However, it remains unknown how unrepaired
      SSBs are recognized by DNA damage response (DDR) pathway, largely because of the
      lack of a feasible experimental system. Here, we demonstrate evidence showing
      that an ATR-dependent checkpoint signaling is activated by a defined plasmid
      based site-specific SSB structure in Xenopus HSS (high-speed supernatant) system.
      Notably, the distinct SSB signaling requires APE2 and canonical checkpoint
      proteins, including ATR, ATRIP, TopBP1, Rad9 and Claspin. Importantly, the SSB
      induced ATR DDR is essential for SSB repair. We and others show that APE2
      interacts with PCNA via its PIP box and preferentially interacts with ssDNA via
      its C-terminus Zf-GRF domain, a conserved motif found in >100 proteins involved
      in DNA/RNA metabolism. Here, we identify a novel mode of APE2-PCNA interaction
      via APE2 Zf-GRF and PCNA C-terminus. Mechanistically, the APE2 Zf-GRF-PCNA
      interaction facilitates 3'-5' SSB end resection, checkpoint protein complex
      assembly, and SSB-induced DDR pathway. Together, we propose that APE2 promotes
      ATR-Chk1 DDR pathway from a single-strand break.

PMID- 29361159
TI  - The effect of an isoflavonid-rich liquorice extract on fermentation,
      methanogenesis and the microbiome in the rumen simulation technique.
AB  - Due to the antimicrobial activity of flavonoids, it has been suggested that they
      may provide a possible alternative to antibiotics to stimulate productivity and
      reduce the environmental load of ruminant agriculture. We hypothesised that an
      extract of liquorice, rich in prenylated isoflavonoids and particularly
      glabridin, might potentially improve the efficiency of nitrogen utilisation and
      reduce methane production in the rumen. When added to a long-term rumen
      simulating fermentor (RUSITEC), liquorice extract at 1 g L-1 decreased ammonia
      production (-51%; P < 0.001) without affecting the overall fermentation process.
      When added at 2 g L-1, decreases in not only ammonia production (-77%; P <
      0.001), but also methane (-27%; P = 0.039) and total VFA production (-15%; P =
      0.003) were observed. These effects in fermentation were probably related to a
      decrease in protozoa numbers, a less diverse bacteria population as well as
      changes in the structure of both the bacterial and archaeal communities. The
      inclusion of an isoflavonoid-rich extract from liquorice in the diet may
      potentially improve the efficiency of the feed utilisation by ruminants.

PMID- 29361161
TI  - A COMPARISON OF OCCUPATIONAL DOSES IN CONVENTIONAL AND INTERVENTIONAL RADIOLOGY
      IN IRAN.
AB  - Occupational exposures in conventional and interventional radiology were
      investigated over a period of 10 years for all radiation workers. The statistical
      analysis carried out on the refined data showed that the average annual effective
      doses in conventional and interventional radiology were 0.28 and 0.59 mSv for
      measurably exposed workers and 0.18 and 0.52 mSv for all monitored workers in
      2014. More than 99.9 and 82.8% of radiation workers in conventional and
      interventional radiology received annual doses less than the public dose limit (1
      mSv) in 2014. Comparing the occupational dose levels of different countries
      (including Iran) in conventional as well as interventional radiology showed a
      poor comparability among them. Regarding the doses above the investigation level,
      the analysis showed that majority of them were due to improper use of personal
      dosimeters (false doses) and only 0.01 and 0.12% of the dose records actually
      crossed the level in conventional and interventional radiology in 2014.

PMID- 29361160
TI  - Glutathione S-Transferase Protein Expression in Different Life Stages of
      Zebrafish (Danio rerio).
AB  - Zebrafish is a widely used animal model in biomedical sciences and toxicology.
      Although evidence for the presence of phases I and II xenobiotic defense
      mechanisms in zebrafish exists on the transcriptional and enzyme activity level,
      little is known about the protein expression of xenobiotic metabolizing enzymes.
      Given the important role of glutathione S-transferases (GSTs) in phase II
      biotransformation, we analyzed cytosolic GST proteins in zebrafish early life
      stages and different organs of adult male and female fish, using a targeted
      proteomics approach. The established multiple reaction monitoring-based assays
      enable the measurement of the relative abundance of specific GST isoenzymes and
      GST classes in zebrafish through a combination of proteotypic peptides and
      peptides shared within the same class. GSTs of the classes alpha, mu, pi and rho
      are expressed in zebrafish embryo as early as 4 h postfertilization (hpf). The
      majority of GST enzymes are present at 72 hpf followed by a continuous increase
      in expression thereafter. In adult zebrafish, GST expression is organ dependent,
      with most of the GST classes showing the highest expression in the liver. The
      expression of a wide range of cytosolic GST isoenzymes and classes in zebrafish
      early life stages and adulthood supports the use of zebrafish as a model organism
      in chemical-related investigations.

PMID- 29361162
TI  - A novel family of tyrosine integrases encoded by the temperate pleolipovirus
      SNJ2.
AB  - Genomes of halophilic archaea typically contain multiple loci of integrated
      mobile genetic elements (MGEs). Despite the abundance of these elements, however,
      mechanisms underlying their site-specific integration and excision have not been
      investigated. Here, we identified and characterized a novel recombination system
      encoded by the temperate pleolipovirus SNJ2, which infects haloarchaeon Natrinema
      sp. J7-1. SNJ2 genome is inserted into the tRNAMet gene and flanked by 14 bp
      direct repeats corresponding to attachment core sites. We showed that SNJ2
      encodes an integrase (IntSNJ2) that excises the proviral genome from its host
      cell chromosome, but requires two small accessory proteins, Orf2 and Orf3, for
      integration. These proteins were co-transcribed with IntSNJ2 to form an operon.
      Homology searches showed that IntSNJ2-type integrases are widespread in
      haloarchaeal genomes and are associated with various integrated MGEs.
      Importantly, we confirmed that SNJ2-like recombination systems are encoded by
      haloarchaea from three different genera and are critical for integration and
      excision. Finally, phylogenetic analysis suggested that IntSNJ2-type recombinases
      belong to a novel family of archaeal integrases distinct from previously
      characterized recombinases, including those from the archaeal SSV- and pNOB8-type
      families.

PMID- 29361163
TI  - Genomic and Expression Analyses Identify a Disease-Modifying Variant for
      Fibrostenotic Crohn's Disease.
AB  - Background and Aims: Crohn's disease [CD] is a chronic inflammatory disease with
      unpredictable behaviour. More than half of CD patients eventually develop
      complications such as stenosis, for which they then require endoscopic dilatation
      or surgery, as no anti-fibrotic drugs are currently available. We aim to identify
      disease-modifying genes associated with fibrostenotic CD. Methods: We performed a
      within-case analysis comparing 'extreme phenotypes' using the Immunochip and
      replication of the top single nucleotide polymorphisms [SNPs] with Agena
      Bioscience in two independent case-control cohorts totalling 322 cases with
      fibrostenotis [recurrent after surgery] and 619 cases with purely inflammatory
      CD. Results: Combined meta-analysis resulted in a genome-wide significant signal
      for SNP rs11861007 [p = 6.0910-11], located on chromosome 16, in lncRNA RP11
      679B19.1, an lncRNA of unknown function, and close to exon 9 of the WWOX gene,
      which codes for WW domain-containing oxidoreductase. We analysed mRNA expression
      of TGF-beta and downstream genes in ileocecal resection material from ten
      patients with and without the WWOX risk allele. Patients carrying the risk allele
      [A] showed enhanced colonic expression of TGF-beta compared to patients
      homozygous for the wild-type [G] allele [p = 0.0079]. Conclusion: We have
      identified a variant in WWOX and in lncRNA RP11-679B19.1 as a disease-modifying
      genetic variant associated with recurrent fibrostenotic CD and replicated this
      association in an independent cohort. WWOX can potentially play a crucial role in
      fibrostenosis in CD, being positioned at the crossroads of inflammation and
      fibrosis.

PMID- 29361164
TI  - Central retinal vein occlusion in temporal arteritis: red sign or red herring?

PMID- 29361165
TI  - Single blood transfusion induces the production of donor-specific alloantibodies
      and regulatory T cells mainly in the spleen.
AB  - Donor-specific blood transfusion is known to induce alloresponses and lead to
      immunosuppression. We examined their underlying mechanisms by employing fully
      allogeneic rat combinations. Transfused recipients efficiently produced
      alloantibodies of the IgM and IgG subclasses directed against donor class I MHC.
      The recipients exhibited active expansion of CD4+ T cells and CD4+FOXP3+
      regulatory T cells (Treg cells), followed by CD45R+ B cells and IgM+ or IgG
      subclass+ antibody-forming cells mainly in the spleen. From 1.5 days, the
      resident MHCII+CD103+ dendritic cells (DCs) in the splenic T-cell area,
      periarterial lymphocyte sheath, formed clusters with recipient BrdU+ or 5-ethynyl
      2'-deoxyuridine+ cells, from which the proliferative response of CD4+ T cells
      originated peaking at 3-4 days. Transfusion-induced antibodies had donor
      passenger cell-depleting activity in vitro and in vivo and could suppress acute
      GvH disease caused by donor T cells. Furthermore, Treg cells significantly
      suppressed mixed leukocyte reactions in a donor-specific manner. In conclusion,
      single blood transfusion efficiently induced a helper T-cell-dependent anti-donor
      class I MHC antibody-forming cell response with immunoglobulin class switching,
      and a donor-specific Treg cell response mainly in the spleen, probably by way of
      the indirect allorecognition via resident DCs. These antibodies and Treg cells
      may be involved, at least partly, in the donor-specific transfusion-induced
      suppression of allograft rejection.

PMID- 29361166
TI  - Intermediate Developmental Phases During Regeneration.
AB  - The initial view that regeneration can be a continuum in terms of regulatory
      mechanisms is gradually changing, and recent evidence points towards the presence
      of discrete regulatory steps and intermediate phases. Furthermore, regeneration
      presents an excellent example of a process generating order and pattern, i.e. a
      self-organization process. It is likely that the process traverses a set of
      intermediate phases before reaching an endpoint. Although some progress has been
      made in deciphering the identity of these intermediate phases, a lot more work is
      needed to derive a comprehensive and complete picture. Here, we discuss the
      intermediate developmental phases in plant regeneration and compare them with the
      possible intermediate developmental phases in animal regeneration.

PMID- 29361168
TI  - Novel stent design for transcatheter mitral valve implantation.
AB  - OBJECTIVES: In this study, results of a functional in vitro study of 2 newly
      developed valved stents for transcatheter mitral valve implantation are
      presented. METHODS: Two novel stent designs, an oval-shaped and a D-shaped stent
      with a strut fixation system were developed. The fixation force of the novel
      stents were tested in vitro in porcine hearts with a tensile test set-up. In
      further experiments, the stents were equipped with a circular valved stent, and
      the valve performances were investigated in a pulsatile heart valve tester.
      RESULTS: Sufficient mean stent fixation forces in the range of 24.2 +/- 0.9 N to
      28.6 +/- 1.9 N were measured for the different stent models. The novel valved
      stents showed good performance in an in vitro pulsatile heart valve tester. A
      sufficient opening area and low opening pressures were measured for all tested
      mitral valved stents. Compared with an established reference valve, the D-shaped
      stent and the oval-shaped valved stent showed a lower systolic transvalvular
      pressure gradient, which indicates slightly greater extent of valvular leakage of
      the closed valved stents. However, the mitral nitinol valved stents demonstrated
      adequate durability. CONCLUSIONS: This study indicates a sufficient annular
      fixation force of the tested transcatheter mitral valve implantation valved stent
      prototypes. Therefore, these mitral valved stents demonstrate a new type of
      mitral valved stent design.

PMID- 29361169
TI  - eComment. New horizons in diagnosing and managing cardiac echinococcosis.

PMID- 29361167
TI  - A novel mechanism causing imbalance of mitochondrial fusion and fission in human
      myopathies.
AB  - Mitochondrial dynamics play an important role in cellular homeostasis and a
      variety of human diseases are linked to its dysregulated function. Here, we
      describe a 15-year-old boy with a novel disease caused by altered mitochondrial
      dynamics. The patient was the second child of consanguineous Jewish parents. He
      developed progressive muscle weakness and exercise intolerance at 6 years of age.
      His muscle biopsy revealed mitochondrial myopathy with numerous ragged red and
      cytochrome c oxidase (COX) negative fibers and combined respiratory chain complex
      I and IV deficiency. MtDNA copy number was elevated and no deletions of the mtDNA
      were detected in muscle DNA. Whole exome sequencing identified a homozygous
      nonsense mutation (p.Q92*) in the MIEF2 gene encoding the mitochondrial dynamics
      protein of 49 kDa (MID49). Immunoblotting revealed increased levels of proteins
      promoting mitochondrial fusion (MFN2, OPA1) and decreased levels of the fission
      protein DRP1. Fibroblasts of the patient showed elongated mitochondria, and
      significantly higher frequency of fusion events, mtDNA abundance and aberrant
      mitochondrial cristae ultrastructure, compared with controls. Thus, our data
      suggest that mutations in MIEF2 result in imbalanced mitochondrial dynamics and a
      combined respiratory chain enzyme defect in skeletal muscle, leading to
      mitochondrial myopathy.

PMID- 29361170
TI  - eComment. Posterior mitral valve leaflet prolapse: one term, several different
      meanings.

PMID- 29361171
TI  - eComment. Narrative therapy for decision making about pectus excavatum treatment:
      Concepts clarification and basic claims demonstration challenge.

PMID- 29361173
TI  - The Changing Face of Noncardia Gastric Cancer Incidence Among US Non-Hispanic
      Whites.
AB  - Background: The initial step for noncardia gastric carcinogenesis is atrophic
      gastritis, driven by either Helicobacter pylori infection or autoimmunity. In
      recent decades, the prevalence rates of these two major causes declined and
      increased, respectively, with changes in Western lifestyles. We therefore
      assessed gastric cancer incidence trends for US race/ethnic groups, 1995-2013.
      Methods: Age-standardized rates (ASRs) from 45 North American Association of
      Central Cancer Tumor Registries were summarized by estimated annual percentage
      change (EAPC) and 95% confidence intervals (CIs). Age period cohort models
      supplemented standard descriptive techniques and projected future trends.
      Results: There were 137 447 noncardia cancers in 4.4 billion person-years of
      observation. Among non-Hispanic whites, the ASR was 2.2 per 100 000 person-years,
      with an EAPC of -2.3% (95% CI = -2.0% to -2.6%). Notwithstanding this overall
      decline, EAPCs rose 1.3% (95% CI = 0.6% to 2.1%) for persons younger than age 50
      years and fell -2.6% (95% CI = -2.4% to -2.9%) for older individuals. These
      converging trends manifested a birth cohort effect more pronounced among women
      than men, with incidence among women born in 1983 twofold (95% CI = 1.1-fold to
      3.6-fold) greater than those born in 1951. Age interaction was also statistically
      significant among Hispanic whites, with slightly increasing vs decreasing EAPCs
      for younger and older individuals, respectively. Incidence declined regardless of
      age for other races. Current trends foreshadow expected reversals in both falling
      incidence and male predominance among non-Hispanic whites. Conclusions: Dysbiosis
      of the gastric microbiome associated with modern living conditions may be
      increasing risk of autoimmune gastritis and consequent noncardia cancer. The
      changing face by age and sex of gastric cancer warrants analytical studies to
      identify potential causal mechanisms.

PMID- 29361174
TI  - Toxicity of Bifenthrin and Mixtures of Bifenthrin Plus Acephate, Imidacloprid,
      Thiamethoxam, or Dicrotophos to Adults of Tarnished Plant Bug (Hemiptera:
      Miridae).
AB  - To assess the toxicity of bifenthrin and four mixtures of insecticides to
      tarnished plant bug, we used an insecticide dip method of green bean to treat
      adults of a laboratory colony; mortality was assessed after 48 h. LC50s for
      imidacloprid, bifenthrin, acephate, thiamethoxam, and dicrotophos were 0.12,
      0.39, 0.62, 0.67, and 3.96 ppm, respectively. LC75s for imidacloprid, bifenthrin,
      acephate, thiamethoxam, and dicrotophos were 0.61, 4.22, 5.10, 2.65, and 7.86
      ppm, respectively. Based on the LC50s and LC75s, dicrotophos was much less toxic
      than the other chemicals tested. PoloMix software was used to determine
      syngerism, antagonism, or addition effects of the mixtures. Three out of four
      analyses of the joint action of bifenthrin plus imidacloprid or acephate or
      dicrotophos showed that toxicity was not independent and not correlated. For
      bifenthrin plus dicrotophos, observed mortality was greater than expected
      mortality at most concentrations suggesting synergism. Mixtures of bifenthrin
      plus imidacloprid and bifenthrin plus acephate showed observed mortality
      significantly less than expected, suggesting antagonism. LC50s for bifenthrin
      plus dicrotophos, acephate, imidacloprid, and thiamethoxam were 0.38, 1.06, 0.17,
      and 0.26 ppm, respectively. LC75s for bifenthrin plus dicrotophos, acephate,
      imidacloprid, and thiamethoxam were 13.61, 13.18, 0.67, and 0.80 ppm,
      respectively. Based on the LC50s and LC75s, bifenthrin plus acephate was 3- to 10
      fold less toxic than the other chemicals tested. Bifenthrin plus acephate is
      frequently used in tank mixes to control tarnished plant bug and other cotton
      pests, and the effectiveness of each individual chemical appears to be reduced in
      one to one ratio mixtures.

PMID- 29361175
TI  - Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal
      Breast Cancer.
AB  - Background: Breast cancer patients with estrogen receptor (ER)-positive disease
      have a continuous long-term risk for fatal breast cancer, but the biological
      factors influencing this risk are unknown. We aimed to determine whether high
      intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of
      fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph
      node-negative breast cancer patients randomly assigned to receive adjuvant
      tamoxifen vs not. The fraction of cancer cells for each ER intensity level was
      scored by breast cancer pathologists, and intratumor heterogeneity of ER was
      calculated using Rao's quadratic entropy and categorized into high and low
      heterogeneity using a predefined cutoff at the second tertile (67%). Long-term
      breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were
      performed using Kaplan-Meier and multivariable Cox proportional hazard modeling
      adjusting for patient and tumor characteristics. Results: A statistically
      significant difference in long-term survival by high vs low intratumor
      heterogeneity of ER was seen for all ER-positive patients (P < .001) and for
      patients with luminal A subtype tumors (P = .01). In multivariable analyses,
      patients with high intratumor heterogeneity of ER had a twofold increased long
      term risk as compared with patients with low intratumor heterogeneity (ER
      positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00;
      luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:
      Patients with high intratumor heterogeneity of ER had an increased long-term risk
      of fatal breast cancer. Interestingly, a similar long-term risk increase was seen
      in patients with luminal A subtype tumors. Our findings suggest that intratumor
      heterogeneity of ER is an independent long-term prognosticator with potential to
      change clinical management, especially for patients with luminal A tumors.

PMID- 29361177
TI  - Development, characterization, and in vitro-in vivo evaluation of polymeric
      nanoparticles containing miconazole and farnesol for treatment of vulvovaginal
      candidiasis.
AB  - Vulvovaginal candidiasis (VVC) is caused mainly by the opportunistic fungus
      Candida albicans, and its yeast to hyphae transition is considered a major
      virulence factor. Farnesol is a molecule that inhibits yeast to hyphae
      transition. The increased incidence of VVC has influenced a need for developing
      new therapeutic strategies. The objective was to develop a mucoadhesive
      nanostructured system composed of miconazole and farnesol co-encapsulated within
      chitosan nanoparticles. The miconazole presented a minimal inhibitory
      concentration (MIC) of 1 MUg/ml against C. albicans. The farnesol was capable of
      inhibiting yeast to hyphae transition at levels greater or equal to 300 MUM. The
      combination of miconazole and farnesol showed no change in miconazole MIC.
      Chitosan nanoparticles containing miconazole and farnesol were prepared by ionic
      gelation and showed favorable characteristics for use on mucous membranes. They
      showed size variation and polydispersion index (PDI) after 30 days, but the
      efficiency of drug encapsulation was maintained. Regarding toxicity in cultured
      fibroblasts (BALB/c 3T3) the nanoparticles were considered nontoxic. The
      nanoparticles showed antifungal activity against the C. albicans strain used with
      MICs of 2.5 MUg/ml and 2 MUg/ml for nanoparticles containing miconazole or
      miconazole/farnesol, respectively. Nanoparticles containing farnesol inhibited
      yeast to hyphae transition at concentrations greater than or equal to 240 MUM.
      The in vivo antifungal activity was assessed in the murine model for VVC. The
      results suggested that chitosan nanoparticles containing miconazole and farnesol
      were effective at inhibiting fungal proliferation. Additionally, chitosan
      nanoparticles containing farnesol were capable of decreasing the pathogenicity of
      infection, demonstrated through the absence of inflammation.

PMID- 29361176
TI  - The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell
      cycle progression and genomic stability.
AB  - FK506 binding proteins (FKBPs) catalyze the interconversion of cis-trans proline
      conformers in proteins. Importantly, FK506 drugs have anti-cancer and
      neuroprotective properties, but the effectors and mechanisms underpinning these
      properties are not well understood because the cellular function(s) of most FKBP
      proteins are unclear. FKBP25 is a nuclear prolyl isomerase that interacts
      directly with nucleic acids and is associated with several DNA/RNA binding
      proteins. Here, we show the catalytic FKBP domain binds microtubules (MTs)
      directly to promote their polymerization and stabilize the MT network.
      Furthermore, FKBP25 associates with the mitotic spindle and regulates entry into
      mitosis. This interaction is important for mitotic spindle dynamics, as we
      observe increased chromosome instability in FKBP25 knockdown cells. Finally, we
      provide evidence that FKBP25 association with chromatin is cell-cycle regulated
      by Protein Kinase C phosphorylation. This disrupts FKBP25-DNA contacts during
      mitosis while maintaining its interaction with the spindle apparatus.
      Collectively, these data support a model where FKBP25 association with chromatin
      and MTs is carefully choreographed to ensure faithful genome duplication.
      Additionally, they highlight that FKBP25 is a MT-associated FK506 receptor and
      potential therapeutic target in MT-associated diseases.

PMID- 29361178
TI  - dropClust: efficient clustering of ultra-large scRNA-seq data.
AB  - Droplet based single cell transcriptomics has recently enabled parallel screening
      of tens of thousands of single cells. Clustering methods that scale for such high
      dimensional data without compromising accuracy are scarce. We exploit Locality
      Sensitive Hashing, an approximate nearest neighbour search technique to develop a
      de novo clustering algorithm for large-scale single cell data. On a number of
      real datasets, dropClust outperformed the existing best practice methods in terms
      of execution time, clustering accuracy and detectability of minor cell sub-types.

PMID- 29361179
TI  - Particle size affects short-term preference behavior of brown-egg laying hens fed
      diets based on corn or barley.
AB  - We studied the influence of particle size of the main cereal of the diet on
      preference behavior by laying hens. Diets formed a 2 * 5 factorial with 2 main
      cereals (corn vs. barley) and 5 grinding sizes of the cereal (4, 6, 8, 10, and 12
      mm screen). Each treatment was replicated 5 times (10 hens each). After a fasting
      period of 8 h, hens received their respective experimental diets from 06.00 to
      14.00 hours. The geometric mean diameter (GMD) and the geometric standard
      deviation of the residuals in the feeder were determined every 2 hours. In
      addition, CP, ash, and Ca contents of the feeds were determined at the start and
      at the end of the experimental period. The experimental design was completely
      randomized with data analyzed as repeated measures with particle size and cereal
      as main effects. The GMD of the original feeds increased with increases in screen
      size and was greater for the barley than for the corn diets. The difference in
      GMD between the original diets and the residuals measured at 2 h intervals
      decreased as the experiment progressed (P < 0.001 for the interaction). Crude
      protein, ash, and Ca concentrated in the coarse fraction of the original diets
      and of the uneaten feed, an effect more pronounced for the minerals. Independent
      of the coarseness of the feed sieve, ash and Ca contents were higher in the
      uneaten feed at 14.00 h than in the original diets. Hens showed a clear
      preference for coarse particles irrespective of the concentration of CP, ash, or
      Ca in the different fractions of the diets. Data showed that birds under-consumed
      Ca during the morning, a period in which the requirements for mineral deposition
      are low. In summary, hens showed a significant preference for coarser particles,
      an effect that was more evident when the cereals were ground coarse. Hens,
      however, did not show any preference for consuming those feed fractions with
      greater CP, ash, or Ca contents.

PMID- 29361180
TI  - Prevalence of Burnout Among Pain Medicine Physicians and Its Potential Effect
      upon Clinical Outcomes in Patients with Oncologic Pain or Chronic Pain of
      Nononcologic Origin.
AB  - Objective: To evaluate the prevalence of burnout among physicians treating
      patients with chronic pain and to assess the potential relationships between the
      presence of burnout and patients' clinical outcomes such as pain relief,
      satisfaction with pain control, and quality of life. Design: An observational,
      prospective, and noncomparative study. Setting: Pain medicine clinics. Subjects:
      Physicians from medical departments involved in the management of chronic pain.
      Patients aged >=18 years who exhibited moderate chronic pain lasting at least
      three months. Methods: Physicians were evaluated with the Maslach Burnout
      Inventory-Human Services Survey (MBI-HSS). Patients were evaluated with the
      Charlson Comorbidity Index, the Brief Pain Inventory-Short Form (BPI-SF), the
      EuroQol-5D (EQ-5D), and ad hoc instruments for evaluating satisfaction with pain
      control, the extent to which the treatment met patients' expectations, and
      subjective impressions of improvement. Results: Of the 301 physician
      participants, 22 (7.3%, 95% confidence interval [CI] = 4.9 to 10.8) met the
      criteria of burnout. Burnout was higher among physicians from pain units, while
      none of the 35 primary care physicians reported burnout. The presence of burnout
      was positively associated with patients' pain relief (odds ratio [OR] = 1.423,
      95% CI = 1.090 to 1.858) but not with satisfaction with pain control or quality
      of life. Of the remaining independent variables, being treated by pain unit
      physicians was significantly associated with worse pain relief (OR = 0.592, 95%
      CI = 0.507 to 0.691), lower satisfaction (beta = -0.680, 95% CI = -0.834 to 
      0.525), and worse quality of life (beta = -4.047, 95% CI = -5.509 to -2.585)
      compared with being treated by physicians from other specialties (e.g.,
      traumatologists, oncologists, etc.). Conclusions: Our study shows a lack of
      negative or clinically relevant (as shown by the negligible to small effect
      sizes) impact of burnout on patient-reported outcomes (namely, pain relief,
      satisfaction, and quality of life) in patients with chronic pain who are treated
      by pain medicine physicians.

PMID- 29361181
TI  - Toward Understanding Person-Place Transactions in Neighborhoods: A Qualitative
      Participatory Geospatial Approach.
AB  - Background and Objectives: Emerging research regarding aging in neighborhoods
      emphasizes the importance of this context for well-being; however, in-depth
      information about the nature of person-place relationships is lacking. The
      interwoven and complex nature of person and place points to methods that can
      examine these relationships in situ and explore meanings attached to places.
      Participatory geospatial methods can capture situated details about place that
      are not verbalized during interviews or otherwise discerned, and qualitative
      methods can explore interpretations, both helping to generate deep understandings
      of the relationships between person and place. This article describes a combined
      qualitative-geospatial approach for studying of older adults in neighborhoods and
      investigates the qualitative-geospatial approach developed, including its utility
      and feasibility in exploring person-place transactions in neighborhoods. Research
      Design and Methods: We developed and implemented a qualitative-geospatial
      approach to explore how neighborhood and person transact to shape sense of social
      connectedness in older adults. Methods included narrative interviews, go-along
      interviews, and global positioning system tracking with activity/travel diary
      completion followed by map-based interviews. We used a variety of data analysis
      methods with attention to fully utilizing diverse forms of data and integrating
      data during analysis. We reflected on and examined the utility and feasibility of
      the approach through a variety of methods. Results: Findings indicate the unique
      understandings that each method contributes, the strengths of the overall
      approach, and the feasibility of implementing the approach. Discussion and
      Implications: The developed approach has strong potential to generate knowledge
      about person-place transactions that can inform practice, planning, policy, and
      research to promote older adults' well-being.

PMID- 29361183
TI  - The Babushkas of Chernobyl.

PMID- 29361182
TI  - Putting Sex Into Context in Later Life: Environmental Disorder and Sexual
      Interest Among Partnered Seniors.
AB  - Background and Objectives: This study examines whether neighborhood and household
      disorder is associated with sexual interest among partnered seniors. Research
      Design and Methods: Analyses use dyadic data from Wave 2 of the National Social
      Life, Health, and Aging Project (NSHAP), a nationally representative sample of
      community-dwelling older adults (2010-2011). Measures of environmental disorder
      were conducted by trained interviewers. Survey data were also linked to census
      tract information from the 2009 American Community Survey. We used actor-partner
      interdependence models to estimate the likelihood of reporting low sexual
      interest. Results: There was no observed association between neighborhood context
      (physical disorder or census tract socioeconomic disadvantage) and sexual
      interest, but husbands were more likely to report low sexual interest if they
      lived in more disorderly households. High marital quality protected against low
      sexual interest, but these evaluations did not mediate or moderate the putative
      effect of household disorder. Discussion and Implications: Regardless of the
      broader neighborhood context, helping older adults maintain an orderly home space
      may help sustain sexual functioning. Future research should consider how various
      features of the environment matter for additional aspects of late-life sexuality.

PMID- 29361184
TI  - Aging in Context.

PMID- 29361185
TI  - This Is My Place.

PMID- 29361187
TI  - The C-S-A gene system regulates hull pigmentation and reveals evolution of
      anthocyanin biosynthesis pathway in rice.
AB  - Floral organs in rice (Oryza sativa) can be purple, brown, or red in color due to
      the accumulation of flavonoids, but the molecular mechanism underlying specific
      organ pigmentation is not clear. Here, we propose a C-S-A gene model for rice
      hull pigmentation and characterize it through genetic, molecular, and metabolomic
      approaches. Furthermore, we conducted phylogenetic studies to reveal the
      evolution of rice color. In this gene system, C1 encodes a R2R3-MYB transcription
      factor and acts as a color-producing gene, and S1 encodes a bHLH protein that
      functions in a tissue-specific manner. C1 interacts with S1 and activates
      expression of A1, which encodes a dihydroflavonol reductase. As a consequence,
      the hull is purple where functional A1 participation leads to high accumulation
      of cyanidin 3-O-glucoside. Loss of function of A1 leads to a brown hull color due
      to accumulation of flavonoids such as hesperetin 5-O-glucoside, rutin, and
      delphinidin 3-O-rutinoside. This shows a different evolutionary pathway of rice
      color in japonica and indica, supporting independent origin of cultivars in each
      subspecies. Our findings provide a complete perspective on the gene regulation
      network of rice color formation and supply the theoretical basis for extended
      application of this beneficial trait.

PMID- 29361188
TI  - Both Weight at Age 20 and Weight Gain Have an Impact on Sleep Disturbances Later
      in Life: Results of the EpiHealth Study.
AB  - Study Objectives: Obesity is often associated with impaired sleep, whereas the
      impact of body mass index (BMI) at younger age and previous weight gain on sleep
      problems remains unknown. Methods: The present study utilized data from the
      Swedish EpiHealth cohort study. A total of 15845 participants (45-75 years)
      filled out an internet-based questionnaire. BMI was calculated from both measured
      data at study time and self-reported data at age 20 from the questionnaire.
      Results: Sleep-related symptoms were most common among obese individuals (BMI >
      30 kg/m2). An association between weight gain and sleep problems was found and
      those with a low BMI at age 20 were most vulnerable to weight gain when it came
      to risk of sleep problems. Among those who were underweight (BMI < 18.5 kg/m2) at
      age 20, weight gain (kg/year) was associated with difficulties initiating sleep
      with an adjusted OR of 2.64 (95% CI: 1.51-4.62) after adjusting for age, sex,
      smoking, alcohol consumption, physical activity, education, and civil status. The
      corresponding adjusted OR's among those who had been normal weight (BMI 18.5
      24.99) and overweight (BMI 25-29.99 kg/m2) at age 20 were 1.89 (1.47-2.45) and
      1.02 (0.48-2.13), respectively. Also difficulties maintaining sleep and snoring
      were most strongly related to weight gain among those who were underweight at age
      20 with decreasing odds with increasing BMI at that age. Conclusions: Sleep
      problems are related to weight gain and obesity. The impact of weight is most
      pronounced among those who had a low BMI when young.

PMID- 29361189
TI  - Obstructive sleep apnea drug therapy: apnea-hypopnea index leaves us high and
      dry.

PMID- 29361191
TI  - Response to Jolobe: 'Molecular diagnostics in FUO'.

PMID- 29361190
TI  - Conserved and species-specific transcription factor co-binding patterns drive
      divergent gene regulation in human and mouse.
AB  - The mouse is widely used as system to study human genetic mechanisms. However,
      extensive rewiring of transcriptional regulatory networks often confounds
      translation of findings between human and mouse. Site-specific gain and loss of
      individual transcription factor binding sites (TFBS) has caused functional
      divergence of orthologous regulatory loci, and so we must look beyond this
      positional conservation to understand common themes of regulatory control.
      Fortunately, transcription factor co-binding patterns shared across species often
      perform conserved regulatory functions. These can be compared to 'regulatory
      sentences' that retain the same meanings regardless of sequence and species
      context. By analyzing TFBS co-occupancy patterns observed in four human and mouse
      cell types, we learned a regulatory grammar: the rules by which TFBS are combined
      into meaningful regulatory sentences. Different parts of this grammar associate
      with specific sets of functional annotations regardless of sequence conservation
      and predict functional signatures more accurately than positional conservation.
      We further show that both species-specific and conserved portions of this grammar
      are involved in gene expression divergence and human disease risk. These findings
      expand our understanding of transcriptional regulatory mechanisms, suggesting
      that phenotypic divergence and disease risk are driven by a complex interplay
      between deeply conserved and species-specific transcriptional regulatory
      pathways.

PMID- 29361193
TI  - Moisture-driven xylogenesis in Pinus ponderosa from a Mojave Desert mountain
      reveals high phenological plasticity.
AB  - Future seasonal dynamics of wood formation in hyperarid environments are still
      unclear. Although temperature-driven extension of the growing season and
      increased forest productivity are expected for boreal and temperate biomes under
      global warming, a similar trend remains questionable in water-limited regions. We
      monitored cambial activity in a montane stand of ponderosa pine (Pinus ponderosa)
      from the Mojave Desert for 2 consecutive years (2015-2016) showing opposite-sign
      anomalies between warm- and cold-season precipitation. After the wet
      winter/spring of 2016, xylogenesis started 2 months earlier compared to 2015,
      characterized by abundant monsoonal (July-August) rainfall and hyperarid spring.
      Tree size did not influence the onset and ending of wood formation, highlighting
      a predominant climatic control over xylem phenological processes. Moisture
      conditions in the previous month, in particular soil water content and dew point,
      were the main drivers of cambial phenology. Latewood formation started roughly at
      the same time in both years; however, monsoonal precipitation triggered the
      formation of more false rings and density fluctuations in 2015. Because of
      uncertainties in future precipitation patterns simulated by global change models
      for the Southwestern United States, the dependency of P. ponderosa on seasonal
      moisture implies a greater conservation challenge than for species that respond
      mostly to temperature conditions.

PMID- 29361192
TI  - Acute ethanol exposure has bidirectional actions on the endogenous neuromodulator
      adenosine in rat hippocampus.
AB  - BACKGROUND AND PURPOSE: Ethanol is a widely used recreational drug with complex
      effects on physiological and pathological brain function. In epileptic patients,
      the use of ethanol can modify seizure initiation and subsequent seizure activity
      with reports of ethanol being both pro- and anticonvulsant. One proposed target
      of ethanol's actions is the neuromodulator adenosine, which is released during
      epileptic seizures to feedback and inhibit the occurrence of subsequent seizures.
      Here, we investigated the actions of acute ethanol exposure on adenosine
      signalling in rat hippocampus. EXPERIMENTAL APPROACH: We have combined
      electrophysiology with direct measurements of extracellular adenosine using
      microelectrode biosensors in rat hippocampal slices. KEY RESULTS: We found that
      ethanol has bidirectional actions on adenosine signalling: depressant
      concentrations of ethanol (50 mM) increased the basal extracellular concentration
      of adenosine under baseline conditions, leading to the inhibition of synaptic
      transmission, but it inhibited adenosine release during evoked seizure activity
      in brain slices. The reduction in activity-dependent adenosine release was in
      part produced by effects on NMDA receptors, although other mechanisms also
      appeared to be involved. Low concentrations of ethanol (10-15 mM) enhanced
      pathological network activity by selectively blocking activity-dependent
      adenosine release. CONCLUSIONS AND IMPLICATIONS: The complex dose-dependent
      actions of ethanol on adenosine signalling could in part explain the mixture of
      pro-convulsant and anticonvulsant actions of ethanol that have previously been
      reported.

PMID- 29361194
TI  - Clinical and Ethical Considerations for Delivering Couple and Family Therapy via
      Telehealth.
AB  - Studies have generally supported telehealth as a feasible, effective, and safe
      alternative to in-office visits. Telehealth may also be of particular benefit to
      couples/families interested in relational treatments, as it addresses some of the
      barriers that may be more prominent for families, such as childcare and
      scheduling difficulties. Therapists interested in expanding their practice to
      include telehealth should understand ethical and practical considerations of this
      modality. This article discusses areas unique to the delivery of telehealth to
      couples and families. Each broad domain is then elaborated upon with case
      examples from actual clinical practice and specific recommendations for
      addressing potential difficulties. Authors recommend further empirical research
      examining differences in modality outcome, as well as feasibility of the
      suggestions proposed here.

PMID- 29361195
TI  - First record on stranding of a live giant squid Architeuthis dux outside Japanese
      waters.

PMID- 29361196
TI  - "Thank You for Including Us!" - Introducing a Community-Based Collaborative
      Approach to Translating Clinic Materials.
AB  - When working with clients in another language, having culturally relevant and
      properly translated clinic materials is vital to effective clinical practice. Not
      having them presents a barrier for bilingual therapists and their clients. This
      paper reviews common translation methods and introduces a multi-level, community
      based approach for translating clinic materials for non-English speaking clients.
      Informed by decolonizing practices, this five-tier method includes members from
      the target community as cultural brokers to verify the accuracy and nuances of
      language for their cultural group, as well as a constant comparative method to
      ensure methodological rigor in the process of inclusion. We present community
      member's feedback and recommendations, as well as discuss advantages and
      challenges of using this collaborative culturally responsive translation method.

PMID- 29361197
TI  - Structured Goal Planning and Supportive Telephone Follow-up in Rheumatology Care:
      Results From a Pragmatic, Stepped-Wedge, Cluster-Randomized Trial.
AB  - OBJECTIVE: To evaluate patient-reported health effects of an add-on structured
      goal-planning and supportive telephone follow-up rehabilitation program compared
      with traditional rehabilitation programs in patients with rheumatic diseases.
      METHODS: In this pragmatic stepped-wedge, cluster-randomized, controlled trial,
      389 patients with rheumatic diseases recruited from 6 rehabilitation centers
      received either traditional rehabilitation or traditional rehabilitation extended
      with an add-on program tailored to individual needs. The add-on program comprised
      a self-management booklet, motivational interviewing in structured individualized
      goal planning, and 4 supportive follow-up phone calls after discharge. Data were
      collected by questionnaires on admission and discharge from rehabilitation stay,
      and at 6 months and 12 months after discharge. The primary outcome was health
      related quality of life (HRQoL) measured by the Patient Generated Index (range 0
      100, where 0 = low). Secondary outcomes included patient-reported health status,
      self-efficacy, pain, fatigue, global disease activity, and motivation for change.
      The main statistical analysis was a linear repeated measures mixed model
      performed on the intent-to-treat population using all available data. RESULTS: A
      significant treatment effect of the add-on intervention on HRQoL was found on
      discharge (mean difference 3.32 [95% confidence interval 0.27, 6.37]; P = 0.03).
      No significant between-group differences were found after 6 or 12 months. Both
      groups showed positive changes in HRQoL following rehabilitation, which gradually
      declined, although the values remained at higher levels after 6 and 12 months
      compared with baseline values. CONCLUSION: The add-on program enhanced the short
      term effect of rehabilitation with respect to patient-specific HRQoL, but it did
      not prolong the effect as intended.

PMID- 29361198
TI  - Food provisioning in Magellanic penguins as inferred from stable isotope ratios.
AB  - RATIONALE: Food provisioning is considered one of the main traits affecting
      offspring fitness. Differences in food provisioning between sexes, particularly
      in dimorphic species, could affect the amount and type of food provided, due to
      differences in the amount of food carried to the nest as a result of differential
      resources exploitation. Quantitative evidence for sexual differences in food
      provisioning by parents in penguins is scarce. The Magellanic penguin is
      moderately sexually dimorphic and breeds along a broad latitudinal range, with
      birds north and south of this range being essentially dietary specialists while
      those at intermediate latitudes consuming a more diverse diet. METHODS: We used
      stable isotope analysis of carbon and nitrogen to examine if there was a
      differential parental contribution to chicks in ten Magellanic penguin colonies
      throughout its latitudinal breeding distribution. We used the heuristic Euclidean
      isotopic distance (ED) and individual isotope distances between the chicks and
      their parents as a proxy for diet similarity (the smaller the distance, the more
      similar the diet). RESULTS: The analysis showed that chicks tended to have a more
      similar diet to that of their male parent and that this pattern was more evident
      at colonies and in seasons where penguins had a more diverse diet, which could be
      explained by differences in diet between parents. Distance in delta15 N values,
      but not in delta13 C values, differed between both sexes and their chicks in all
      the pairs sampled, suggesting that delta15 N values drive the differences found
      in ED between chicks and their parents. CONCLUSIONS: We have developed an
      approach that provides the first assessment of the extent of differential food
      provisioning between male and female Magellanic penguins. Results suggest chicks
      have a diet more similar to that of their male parent, probably related to the
      higher trophic level of male penguin prey.

PMID- 29361199
TI  - Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor
      Receptor alpha Monoclonal Antibody: Long-Term Safety and Efficacy in Patients
      With Rheumatoid Arthritis.
AB  - OBJECTIVE: Mavrilimumab, a human monoclonal antibody, targets granulocyte
      macrophage colony-stimulating factor receptor alpha. We undertook to determine
      the long-term safety and efficacy of mavrilimumab in rheumatoid arthritis
      patients in 2 phase IIb studies (1071 and 1107) and in 1 open-label extension
      study (ClinicalTrials.gov identifier: NCT01712399). METHODS: In study 1071,
      patients with an inadequate response to disease-modifying antirheumatic drugs
      (DMARDs) received mavrilimumab (30, 100, or 150 mg) or placebo every other week
      plus methotrexate. In study 1107, patients with an inadequate response to anti
      tumor necrosis factor agents and/or DMARDs received 100 mg mavrilimumab every
      other week or 50 mg golimumab every 4 weeks plus methotrexate. Patients entering
      the open-label extension study received 100 mg mavrilimumab every other week plus
      methotrexate. Long-term safety and efficacy of mavrilimumab were assessed.
      RESULTS: A total of 442 patients received mavrilimumab (14 of 245 patients from
      study 1071, 9 of 70 patients from study 1107, and 52 of 397 patients from the
      open-label extension study discontinued mavrilimumab treatment throughout the
      studies). The cumulative safety exposure was 899 patient-years; the median
      duration of mavrilimumab treatment was 2.5 years (range 0.1-3.3 years). The most
      common treatment-emergent adverse events (AEs) were nasopharyngitis (n = 69; 7.68
      per 100 patient-years) and bronchitis (n = 51; 5.68 per 100 patient-years). At
      weeks 74 and 104, 3.5% and 6.2% of patients, respectively, demonstrated reduction
      in forced expiratory volume in 1 second, while 2.9% and 3.4% of patients,
      respectively, demonstrated reduction in forced vital capacity (>20% reduction
      from baseline to <80% predicted). Most pulmonary changes were transient and only
      infrequently associated with AEs. Mavrilimumab at 100 mg every other week
      demonstrated sustained efficacy; at week 122, 65.0% of patients achieved a
      Disease Activity Score in 28 joints using the C-reactive protein level (DAS28
      CRP) of <3.2, and 40.6% of patients achieved a DAS28-CRP of <2.6. CONCLUSION:
      Long-term treatment with mavrilimumab maintained response and was well-tolerated
      with no increased incidence of treatment-emergent AEs. Safety data were
      comparable with those from both phase IIb qualifying studies.

PMID- 29361200
TI  - Improving Mortality in End-Stage Renal Disease Due to Granulomatosis With
      Polyangiitis (Wegener's) From 1995 to 2014: Data From the United States Renal
      Data System.
AB  - OBJECTIVE: To examine temporal trends in mortality rates in a large nationwide
      cohort of patients with end-stage renal disease (ESRD) due to granulomatosis with
      polyangiitis (Wegener's) (GPA-ESRD). METHODS: We identified cases of GPA-ESRD
      reported in the US Renal Data System between 1995 and 2014, using coding by
      nephrologists for the cause of ESRD. The cohort was divided into four 5-year
      subcohorts based on the year of onset of ESRD (1995-1999, 2000-2004, 2005-2009,
      and 2010-2014) to assess trends in mortality rates and hazard ratios (HRs) for
      overall death and cause-specific death, adjusting for potential confounders.
      RESULTS: Between 1995 and 2014, there were 5,929 incident cases of GPA-ESRD. The
      mortality rate (incidence per 100 patient-years) declined from 19.0 in 1995-1999
      to 15.3 in 2010-2014 (P for trend = 0.01). The multivariable-adjusted HR for
      mortality in the 2010-2014 cohort was 0.77 (95% confidence interval [95% CI] 0.66
      0.90) (P for trend < 0.001 versus the 1995-1999 cohort). The corresponding cause
      specific HRs for mortality, after accounting for competing risk, were 0.61 (95%
      CI 0.47-0.80) for CVD-related death and 0.42 (95% CI 0.28-0.63) for death due to
      infection (P for trend < 0.001). CONCLUSION: In this study of nearly all patients
      in whom GPA-ESRD developed in the US over 2 decades, we observed significant
      improvements in mortality among GPA-ESRD patients. The number of cause-specific
      deaths due to CVD and the number due to infections declined significantly during
      the study period. These findings are encouraging and likely reflect improved
      management of both GPA and ESRD.

PMID- 29361201
TI  - Convergence of nuclear magnetic shieldings and one-bond 1 J(11 B1 H) indirect
      spin-spin coupling constants in small boron molecules.
AB  - Self-consistent field Hartree-Fock, density functional theory, and coupled
      cluster calculations of the nuclear magnetic shielding constants of BH and BH3
      molecules have been conducted to characterize the convergence of individual
      results obtained with correlation-consistent and polarization-consistent basis
      sets. The individual 11 B and 1 H NMR parameters were estimated in the complete
      basis set limit and compared with benchmark results. Only the KT3 density
      functional accurately reproduced 11 B shielding in BH molecule.

PMID- 29361202
TI  - Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic
      Review.
AB  - OBJECTIVE: Chikungunya virus infection is a rapidly emerging global viral
      infection that can cause chronic, debilitating arthritis that in some ways mimics
      rheumatoid arthritis. The aim of this study was to evaluate the available
      evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that
      is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya
      arthritis. METHODS: A systematic literature search was performed to identify all
      published trials that evaluated MTX as monotherapy or combination therapy in
      patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane
      Library databases were searched from study inception to August 2017. We also
      searched Google Scholar, the International Clinical Trials Registry Platform
      Search Portal, and clinicaltrials.gov. RESULTS: Among 131 possibly relevant
      studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a
      non-controlled prospective study, and 1 was an unblinded randomized clinical
      trial of combination MTX therapy. In the randomized clinical trial, triple
      therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to
      hydroxychloroquine monotherapy, as assessed by the mean +/- SD Disease Activity
      Score in 28 joints using the erythrocyte sedimentation rate (3.39 +/- 0.87 versus
      4.74 +/- 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 +/
      0.31 versus 1.88 +/- 0.47; P < 0.0001). CONCLUSION: The number of available
      studies is limited, but taken together, these studies demonstrate that MTX is
      sufficiently efficacious to justify further study of MTX for the treatment of
      chronic chikungunya arthritis. The trials lacked rigorous study designs and used
      different treatment strategies and outcome measures. This systematic review
      underscores the need for randomized, prospective, placebo-controlled studies of
      MTX monotherapy for the treatment of chronic chikungunya arthritis.

PMID- 29361203
TI  - The Association Between HLA Genetic Susceptibility Markers and Sonographic
      Enthesitis in Psoriatic Arthritis.
AB  - OBJECTIVE: Enthesitis is an important pathophysiologic component of psoriatic
      arthritis (PsA). HLA genes are implicated in the pathogenesis of PsA. Little is
      known about the relationship between HLA genetic susceptibility markers and
      enthesitis in PsA patients. Our aim was to examine the association between HLA
      genetic susceptibility markers and sonographic enthesitis in PsA. METHODS: A
      cross-sectional analysis was conducted in patients with PsA. Sonographic
      enthesitis was assessed according to the Madrid Sonography Enthesitis Index
      scoring system. HLA genotyping was performed using sequence-specific
      oligonucleotide probes. The association between 6 HLA susceptibility markers of
      PsA and the severity of sonographic enthesitis was assessed using multivariate
      regression models adjusted for age, sex, body mass index, and disease duration.
      RESULTS: Two hundred twenty-five patients were included, 57.8% of whom were men.
      The mean +/- SD age was 56.1 +/- 12.7 years, and the mean +/- SD PsA duration was
      16.9 +/- 12.3 years. In the multivariate regression model, HLA-B*27 was
      associated with a higher enthesitis score (beta = 4.24 [95% confidence interval
      {95% CI} 0.02, 8.46]), and the interaction between HLA-B*27 and PsA duration was
      statistically significant, showing an increasing effect of HLA-B*27 with longer
      PsA duration (beta = 4.62 [95% CI 1.38, 7.86]). CONCLUSION: HLA-B*27 is
      associated with more severe sonographic enthesitis in PsA, particularly in
      patients with longer disease duration. This finding highlights the possible role
      of genetic variants in predisposing to PsA subphenotypes.

PMID- 29361204
TI  - Editorial: Lessons Learned From Chikungunya in the Americas.

PMID- 29361205
TI  - Twin DNA Methylation Profiling Reveals Flare-Dependent Interferon Signature and B
      Cell Promoter Hypermethylation in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) has limited monozygotic twin
      concordance, implying a role for pathogenic factors other than genetic variation,
      such as epigenetic changes. Using the disease-discordant twin model, we
      investigated genome-wide DNA methylation changes in sorted CD4+ T cells,
      monocytes, granulocytes, and B cells in twin pairs with at least 1 SLE-affected
      twin. METHODS: Peripheral blood obtained from 15 SLE-affected twin pairs (6
      monozygotic and 9 dizygotic) was processed using density-gradient centrifugation
      for the granulocyte fraction. CD4+ T cells, monocytes, and B cells were further
      isolated using magnetic beads. Genome-wide DNA methylation was analyzed using
      Infinium HumanMethylation450K BeadChips. When comparing probes from SLE-affected
      twins and co-twins, differential DNA methylation was considered statistically
      significant when the P value was less than 0.01 and biologically relevant when
      the median DNA methylation difference was >7%. Findings were validated by
      pyrosequencing and replicated in an independent case-control sample. RESULTS: In
      paired analyses of twins discordant for SLE restricted to the gene promoter and
      start region, we identified 55, 327, 247, and 1,628 genes with differentially
      methylated CpGs in CD4+ T cells, monocytes, granulocytes, and B cells,
      respectively. All cell types displayed marked hypomethylation in interferon
      regulated genes, such as IFI44L, PARP9, and IFITM1, which was more pronounced in
      twins who experienced a disease flare within the past 2 years. In contrast to
      what was observed in the other cell types, differentially methylated CpGs in B
      cells were predominantly hypermethylated, and the most important upstream
      regulators included TNF and EP300. CONCLUSION: Hypomethylation of interferon
      regulated genes occurs in all major cellular compartments in SLE-affected twins.
      The observed B cell promoter hypermethylation is a novel finding with potential
      significance in SLE pathogenesis.

PMID- 29361207
TI  - The Ratio of Blood T Follicular Regulatory Cells to T Follicular Helper Cells
      Marks Ectopic Lymphoid Structure Formation While Activated Follicular Helper T
      Cells Indicate Disease Activity in Primary Sjogren's Syndrome.
AB  - OBJECTIVE: To investigate whether the balance of blood follicular helper T (Tfh)
      cells and T follicular regulatory (Tfr) cells can provide information about
      ectopic lymphoid neogenesis and disease activity in primary Sjogren's syndrome
      (SS). METHODS: We prospectively recruited 56 patients clinically suspected of
      having SS. Sixteen of these patients subsequently fulfilled the American-European
      Consensus Group criteria for SS and were compared to 16 patients with non-SS
      sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were
      analyzed to study Tfr cells and subsets of Tfh cells in both compartments.
      RESULTS: Patients with primary SS had normal Tfh cell counts in peripheral blood;
      however, activated programmed death 1-positive (PD-1+) inducible costimulator
      positive (ICOS+) Tfh cells in peripheral blood were strongly associated with
      disease activity assessed by the European League Against Rheumatism Sjogren's
      Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood
      Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs,
      being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell
      infiltration in MSGs, and was especially increased in patients with focal
      sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio
      allowed discrimination between SS patients and healthy donors with excellent
      accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P =
      0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients
      investigated for sicca symptoms, thus highlighting the potential clinical value
      of this marker. CONCLUSION: The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh
      cells constitute potential novel biomarkers for different features of primary SS.
      While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid
      neogenesis, activated Tfh cells indicate disease activity.

PMID- 29361208
TI  - Peroxiredoxin System of Aspergillus nidulans Resists Inactivation by High
      Concentration of Hydrogen Peroxide-Mediated Oxidative Stress.
AB  - Most eukaryotic peroxiredoxins (Prxs) are readily inactivated by a high
      concentration of hydrogen peroxide (H2O2) during catalysis owing to their "GGLG"
      and "YF" motifs. However, such oxidative stress sensitive motifs were not found
      in the previously identified filamentous fungal Prxs. Additionally, the
      information on filamentous fungal Prxs is limited and fragmentary. Herein, we
      cloned and gained insight into Aspergillus nidulans Prx (An.PrxA) in the aspects
      of protein properties, catalysis characteristics, and especially H2O2
      tolerability. Our results indicated that An.PrxA belongs to the newly defined
      family of typical 2-Cys Prxs with a marked characteristic that the "resolving"
      cysteine (CR) is invertedly located preceding the "peroxidatic" cysteine (CP) in
      amino acid sequences. The inverted arrangement of CR and CP can only be found
      among some yeast, bacterial, and filamentous fungal deduced Prxs. The most
      surprising characteristic of An.PrxA is its extraordinary ability to resist
      inactivation by extremely high concentrations of H2O2, even that approaching 600
      mM. By screening the H2O2-inactivation effects on the components of Prx systems,
      including Trx, Trx reductase (TrxR), and Prx, we ultimately determined that it is
      the robust filamentous fungal TrxR rather than Trx and Prx that is responsible
      for the extreme H2O2 tolerence of the An.PrxA system. This is the first
      investigation on the effect of the electron donor partner in the H2O2
      tolerability of the Prx system.

PMID- 29361206
TI  - Effects and moderators of psychosocial interventions on quality of life, and
      emotional and social function in patients with cancer: An individual patient data
      meta-analysis of 22 RCTs.
AB  - OBJECTIVE: This individual patient data (IPD) meta-analysis aimed to evaluate the
      effects of psychosocial interventions (PSI) on quality of life (QoL), emotional
      function (EF), and social function (SF) in patients with cancer, and to study
      moderator effects of demographic, clinical, personal, and intervention-related
      characteristics. METHODS: Relevant studies were identified via literature
      searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible
      randomized controlled trials. Linear mixed-effect model analyses were used to
      study intervention effects on the post-intervention values of QoL, EF, and SF (z
      scores), adjusting for baseline values, age, and cancer type. We studied
      moderator effects by testing interactions with the intervention for demographic,
      clinical, personal, and intervention-related characteristics, and conducted
      subsequent stratified analyses for significant moderator variables. RESULTS: PSI
      significantly improved QoL (beta = 0.14,95%CI = 0.06;0.21), EF (beta = 0.13,95%CI
      = 0.05;0.20), and SF (beta = 0.10,95%CI = 0.03;0.18). Significant differences in
      effects of different types of PSI were found, with largest effects of
      psychotherapy. The effects of coping skills training were moderated by age,
      treatment type, and targeted interventions. Effects of psychotherapy on EF may be
      moderated by cancer type, but these analyses were based on 2 randomized
      controlled trials with small sample sizes of some cancer types. CONCLUSIONS: PSI
      significantly improved QoL, EF, and SF, with small overall effects. However, the
      effects differed by several demographic, clinical, personal, and intervention
      related characteristics. Our study highlights the beneficial effects of coping
      skills training in patients treated with chemotherapy, the importance of targeted
      interventions, and the need of developing interventions tailored to the specific
      needs of elderly patients.

PMID- 29361209
TI  - Delivery of Chicken Egg Ovalbumin to Dendritic Cells by Listeriolysin O-Secreting
      Vegetative Bacillus subtilis.
AB  - Listeriolysin O (LLO), one of the most immunogenic proteins of Listeria
      monocytogenes and its main virulence factor, mediates bacterial escape from the
      phagosome of the infected cell. Thus, its expression in a nonpathogenic bacterial
      host may enable effective delivery of heterologous antigens to the host cell
      cytosol and lead to their processing predominantly through the cytosolic MHC
      class I presentation pathway. The aim of this project was to characterize the
      delivery of a model antigen, chicken egg ovalbumin (OVA), to the cytosol of
      dendritic cells by recombinant Bacillus subtilis vegetative cells expressing LLO.
      Our work indicated that LLO produced by non-sporulating vegetative bacteria was
      able to support OVA epitope presentation by MHC I molecules on the surface of
      antigen presenting cells and consequently influence OVA-specific cytotoxic T cell
      activation. Additionally, it was proven that the genetic context of the epitope
      sequence is of great importance, as only the native full-sequence OVA fused to
      the N-terminal fragment of LLO was sufficient for effective epitope delivery and
      activation of CD8+ lymphocytes. These results demonstrate the necessity for
      further verification of the fusion antigen potency of enhancing the MHC I
      presentation, and they prove that LLO-producing B. subtilis may represent a novel
      and attractive candidate for a vaccine vector.

PMID- 29361210
TI  - Preparation and Antioxidant Activities In Vitro of a Designed Antioxidant Peptide
      from Pinctada fucata by Recombinant Escherichia coli.
AB  - An antioxidant peptide derived from Pinctada fucata meat using an Alcalase2.4L
      enzymatic hydrolysis method (named AOP) and identified by LC-TOF-MS has promising
      clinical potential for generating cosmetic products that protect skin from
      sunshine. To date, there have been few published studies investigating the
      structure-activity relationship in these peptides. To prepare antioxidant
      peptides better and improve their stability, the design and expression of an
      antioxidant peptide from Pinctada fucata (named DSAOP) was studied. The peptide
      contains a common precursor of an expression vector containing an alpha-helix
      tandemly linked according to the BamHI restriction sites. The DNA fragments
      encoding DSAOP were synthesized and subcloned into the expression vector pET-30a
      (+), and the peptide was expressed mostly as soluble protein in recombinant
      Escherichia coli. Meanwhile, the DPPH radical scavenging activity, superoxide
      radical scavenging activity, and hydroxyl radical scavenging activity of DSAOP
      IC50 values were 0.136 +/- 0.006, 0.625 +/- 0.025, and 0.306 +/- 0.015 mg/ml,
      respectively, with 2-fold higher DPPH radical scavenging activity compared with
      chemosynthesized AOP (p < 0.05), as well as higher superoxide radical scavenging
      activity compared with natural AOP (p < 0.05). This preparation method was at the
      international advanced level. Furthermore, pilot-scale production results showed
      that DSAOP was expressed successfully in fermenter cultures, which indicated that
      the design strategy and expression methods would be useful for obtaining
      substantial amounts of stable peptides at low costs. These results showed that
      DSAOP produced with recombinant Escherichia coli could be useful in cosmetic skin
      care products, health foods, and pharmaceuticals.

PMID- 29361211
TI  - Bespoke Pretargeted Nanoradioimmunotherapy for the Treatment of Non-Hodgkin
      Lymphoma.
AB  - Non-Hodgkin lymphoma (NHL) is one of the most common types of hematologic
      malignancies. Pretargeted radioimmunotherapy (PRIT), the sequential
      administration of a bispecific antibody-based primary tumor-targeting component
      followed by a radionucleotide-labeled treatment effector, has been developed to
      improve the treatment efficacy and to reduce the side effects of conventional
      RIT. Despite the preclinical success of PRIT, clinical trials revealed that the
      immunogenicity of the bispecific antibody as well as the presence of competing
      endogenous effector molecules often compromised the treatment. One strategy to
      improve PRIT is to utilize bio-orthogonal ligation reactions to minimize
      immunogenicity and improve targeting. Herein, we report a translatable
      pretargeted nanoradioimmunotherapy strategy for the treatment of NHL. This
      pretargeting system is composed of a dibenzylcyclooctyne (DBCO)-functionalized
      anti-CD20 antibody (alpha-CD20) tumor-targeting component and an azide- and
      yttrium-90-(90Y) dual-functionalized dendrimer. The physicochemical properties of
      both pretargeting components have been extensively studied. We demonstrated that
      an optimized dual-functionalized dendrimer can undergo rapid strain-promoted
      azide-alkyne cycloaddition with the DBCO-functionalized alpha-CD20 at the
      physiological conditions. The treatment effector in our pretargeting system can
      not only selectively deliver radionucleotides to the target tumor cells but also
      increase the complement-dependent cytotoxicity of alpha-CD20 and thus enhance the
      antitumor effects, as justified by comprehensive in vitro and in vivo studies in
      mouse NHL xenograft and disseminated models.

PMID- 29361212
TI  - Biomimetic Optical Cellulose Nanocrystal Films with Controllable Iridescent Color
      and Environmental Stimuli-Responsive Chromism.
AB  - As a wise and profound teacher, nature provides numerous creatures with rich
      colors to us. To biomimic structural colors in nature as well as color changes
      responsive to environmental stimuli, there is a long way to go for the
      development of free-standing photonic films from natural polymers. Herein, a
      highly flexible, controllably iridescent, and multistimuli-responsive cellulose
      nanocrystal (CNC) film is prepared by simply introducing a small molecule as both
      plasticizer and hygroscopic agent. The presence of the additive does not block
      the self-assembly of CNC in aqueous solution but results in the enhancement of
      its mechanical toughness, making it possible to obtain free-standing iridescent
      CNC films with tunable structural colors. In response to environmental humidity
      and mechanical compression, such films can change structural colors smoothly by
      modulating their chiral nematic structures. Notably, the chromism is reversible
      by alternately changing relative humidity between 16 and 98%, mimicking the
      longhorn beetle Tmesisternus isabellae. This chromic effect enables various
      applications of the biofilms in colorimetric sensors, anticounterfeiting
      technology, and decorative coatings.

PMID- 29361213
TI  - Matrix Metalloproteinase 9 Displays a Particular Time Response to Acute Stress:
      Variation in Its Levels and Activity Distribution in Rat Hippocampus.
AB  - A single stress exposure facilitates memory formation through neuroplastic
      processes that reshape excitatory synapses in the hippocampus, probably requiring
      changes in extracellular matrix components. We tested the hypothesis that matrix
      metalloproteinase 9 (MMP-9), an enzyme that degrades components of extracellular
      matrix and synaptic proteins such as beta-dystroglycan (beta-DG43), changes their
      activity and distribution in rat hippocampus during the acute stress response.
      After 2.5 h of restraint stress, we found (i) increased MMP-9 levels and
      potential activity in whole hippocampal extracts, accompanied by beta-DG43
      cleavage, and (ii) a significant enhancement of MMP-9 immunoreactivity in
      dendritic fields such as stratum radiatum and the molecular layer of hippocampus.
      After 24 h of stress, we found that (i) MMP-9 net activity rises at somatic
      field, i.e., stratum pyramidale and granule cell layers, and also at synaptic
      field, mainly stratum radiatum and the molecular layer of hippocampus, and (ii)
      hippocampal synaptoneurosome fractions are enriched with MMP-9, without variation
      of its potential enzymatic activity, in accordance with the constant level of
      cleaved beta-DG43. These findings indicate that stress triggers a peculiar timing
      response in the MMP-9 levels, net activity, and subcellular distribution in the
      hippocampus, suggesting its involvement in the processing of substrates during
      the stress response.

PMID- 29361214
TI  - Molecular Simulations of the Hydration Behavior of a Zwitterion Brush Array and
      Its Antifouling Property in an Aqueous Environment.
AB  - We carried out umbrella sampling and molecular dynamics (MD) simulations to
      investigate molecular interactions between sulfobetaine zwitterions or between
      sulfobetaine brushes in different media. Simulation results show that it is more
      energetically favorable for the two sulfobetaine zwitterions or brushes to be
      fully hydrated in aqueous solutions than in vacuum where strong ion pairs are
      formed. Structural properties of the hydrated sulfobetaine brush array and its
      antifouling behavior against a foulant gel are subsequently studied through
      steered MD simulations. We find that sulfobetaine brush arrays with different
      grafting densities have different structures and antifouling mechanisms. At a
      comparably higher grafting density, the sulfobetaine brush array exhibits a more
      organized structure which can hold a tightly bound hydration water layer at the
      interface. Compression of this hydration layer results in a strong repulsive
      force. However, at a comparably lower grafting density, the brush array exhibits
      a randomly oriented structure in which the antifouling of the brush array is
      through the deformation of the sulfobetaine branches.

PMID- 29361215
TI  - ATPbind: Accurate Protein-ATP Binding Site Prediction by Combining Sequence
      Profiling and Structure-Based Comparisons.
AB  - Protein-ATP interactions are ubiquitous in a wide variety of biological
      processes. Correctly locating ATP binding sites from protein information is an
      important but challenging task for protein function annotation and drug
      discovery. However, there is no method that can optimally identify ATP binding
      sites for different proteins. In this study, we report a new composite predictor,
      ATPbind, for ATP binding sites by integrating the outputs of two template-based
      predictors (i.e., S-SITE and TM-SITE) and three discriminative sequence-driven
      features of proteins: position specific scoring matrix, predicted secondary
      structure, and predicted solvent accessibility. In ATPbind, we assembled multiple
      support vector machines (SVMs) based on a random undersampling technique to cope
      with the serious imbalance phenomenon between the numbers of ATP binding sites
      and of non-ATP binding sites. We also constructed a new gold-standard benchmark
      data set consisting of 429 ATP binding proteins from the PDB database to evaluate
      and compare the proposed ATPbind with other existing predictors. Starting from a
      query sequence and predicted I-TASSER models, ATPbind can achieve an average
      accuracy of 72%, covering 62% of all ATP binding sites while achieving a Matthews
      correlation coefficient value that is significantly higher than that of other
      state-of-the-art predictors.

PMID- 29361216
TI  - Medical Imaging for the Tracking of Micromotors.
AB  - Micro/nanomotors are useful tools for several biomedical applications, including
      targeted drug delivery and minimally invasive microsurgeries. However, major
      challenges such as in vivo imaging need to be addressed before they can be safely
      applied on a living body. Here, we show that positron emission tomography (PET),
      a molecular imaging technique widely used in medical imaging, can also be used to
      track a large population of tubular Au/PEDOT/Pt micromotors. Chemisorption of an
      iodine isotope onto the micromotor's Au surface rendered them detectable by PET,
      and we could track their movements in a tubular phantom over time frames of up to
      15 min. In a second set of experiments, micromotors and the bubbles released
      during self-propulsion were optically tracked by video imaging and bright-field
      microscopy. The results from direct optical tracking agreed with those from PET
      tracking, demonstrating that PET is a suitable technique for the imaging of large
      populations of active micromotors in opaque environments, thus opening
      opportunities for the use of this mature imaging technology for the in vivo
      localization of artificial swimmers.

PMID- 29361217
TI  - Progress in the Development of Preventative Drugs for Cisplatin-Induced Hearing
      Loss.
AB  - Cisplatin is a highly effective treatment for malignant cancers and has become a
      cornerstone in chemotherapeutic regimens. Unfortunately, its use in the clinic is
      often coupled with a high incidence of severe hearing loss. Over the past few
      decades, enormous effort has been put forth to find protective agents that
      selectively protect against the ototoxic side effects of cisplatin and do not
      interfere with its antitumoral activity. Many therapies have been successful in
      preclinical work, but only a few have shown any protection in the clinic, and
      none have been approved by the FDA. This review summarizes the clinical and
      preclinical studies of the most effective small-molecule candidates currently in
      clinical trials, while also detailing their molecular mechanisms of action, to
      gain insight for future drug development in the field.

PMID- 29361218
TI  - Single Site Fluorination of the GM4 Ganglioside Epitope Upregulates
      Oligodendrocyte Differentiation.
AB  - Relapsing multiple sclerosis is synonymous with demyelination, and thus,
      suppressing and or reversing this process is of paramount clinical significance.
      While insulating myelin sheath has a large lipid composition (ca. 70-80%), it
      also has a characteristically large composition of the sialosylgalactosylceramide
      gangliosde GM4 present. In this study, the effect of the carbohydrate epitope on
      oligodendrocyte differentiation is determined. While the native epitope had no
      impact on oligodendroglial cell viability, a single site OH -> F substitution is
      the structural basis of a significant increase in ATP production that is optimal
      at 50 MUg/mL. From a translational perspective, this subtle change increases the
      amount of MBP+ oligodendrocytes compared to the control studies and may open up
      novel therapeutic remyelination strategies.

PMID- 29361219
TI  - Accessibility of Protein-Bound Chlorophylls Probed by Dynamic Electron
      Polarization.
AB  - The possibility to probe the accessibility of sites of proteins represents an
      important point to explore their interactions with specific substrates in
      solution. The dynamic electron polarization of nitroxide radicals induced by
      excited triplet states of organic molecules is a phenomenon that is known to
      occur in aqueous solutions. The interaction within the radical-triplet pair
      causes a net emissive dynamic electron polarization of the nitroxide radical,
      that can be detected by means of time-resolved electron paramagnetic resonance
      (TR-EPR) spectroscopy. We have exploited this effect to prove the accessibility
      of chlorophylls bound to a protein, namely, the water-soluble chlorophyll protein
      WSCP. The results have important implications for topological studies in
      macromolecules.

PMID- 29361221
TI  - Design Rules for Graphene and Carbon Nanotube Solvents and Dispersants.
AB  - The constantly widening industrial applications of carbon-based nanomaterials
      puts into sharp perspective the lack of true solvents in which the materials
      spontaneously exfoliate to individual molecules. This work shows that the
      different geometry of graphene compared to that of carbon nanotubes can change
      the potency of a molecule to act as a solvent or dispersant. Through analysis of
      the structure/function relationships, we derive a number of design rules that
      will aid the identification of the best solvent or dispersant candidates.

PMID- 29361220
TI  - Tundrenone: An Atypical Secondary Metabolite from Bacteria with Highly Restricted
      Primary Metabolism.
AB  - Methane-oxidizing bacteria, aerobes that utilize methane as their sole carbon and
      energy source, are being increasingly studied for their environmentally
      significant ability to remove methane from the atmosphere. Their genomes indicate
      that they also have a robust and unusual secondary metabolism. Bioinformatic
      analysis of the Methylobacter tundripaludum genome identified biosynthetic gene
      clusters for several intriguing metabolites, and this report discloses the
      structural and genetic characterization of tundrenone, one of these metabolites.
      Tundrenone is a highly oxidized metabolite that incorporates both a modified
      bicyclic chorismate-derived fragment and a modified lipid tail bearing a
      beta,gamma-unsaturated alpha-hydroxy ketone. Tundrenone has been genetically
      linked to its biosynthetic gene cluster, and quorum sensing activates its
      production. M. tundripaludum's genome and tundrenone's discovery support the idea
      that additional studies of methane-oxidizing bacteria will reveal new naturally
      occurring molecular scaffolds and the biosynthetic pathways that produce them.

PMID- 29361222
TI  - Conformational Change-Induced Fluorescence of Bovine Serum Albumin-Gold
      Complexes.
AB  - We report new findings on the red fluorescent (lambdaem = 640 nm) bovine serum
      albumin (BSA)-gold (Au) compound initially described by Xie et al. (J. Am. Chem.
      Soc. 2009, 131, 888-889) as Au25 nanoclusters. The BSA-Au compounds were further
      reducible to yield nanoparticles, suggesting that these compounds were BSA
      cationic Au complexes. We examined the correlations between BSA conformations (pH
      induced as well as denatured) and the resulting fluorescence of BSA-Au complexes,
      to understand the possible cationic Au binding sites. The red fluorescence of the
      BSA-Au complex was associated with a particular isoform of BSA, the aged form (pH
      > 10) of the five pH-dependent BSA conformations, while the other conformations,
      expanded (pH < 2.7), fast (2.7 < pH < 4.3), normal (4.3 < pH < 8), and basic (8 <
      pH < 10) did not result in red fluorescence. There could be internal energy
      transfer mechanisms to produce red fluorescence, deduced from excitation-emission
      map measurements. The ensemble minimum number of Au(III) per BSA to yield red
      fluorescence was <7. We illustrate the presence of multiple specific Au binding
      sites in BSA, and present an interpretation of the fluorescence of the BSA-Au
      complex, alternative to a single-site nucleation of a neutral Au25 nanocluster.

PMID- 29361223
TI  - Phonon Driven Floquet Matter.
AB  - The effect of electron-phonon coupling in materials can be interpreted as a
      dressing of the electronic structure by the lattice vibration, leading to
      vibrational replicas and hybridization of electronic states. In solids, a
      resonantly excited coherent phonon leads to a periodic oscillation of the atomic
      lattice in a crystal structure bringing the material into a nonequilibrium
      electronic configuration. Periodically oscillating quantum systems can be
      understood in terms of Floquet theory, which has a long tradition in the study of
      semiclassical light-matter interaction. Here, we show that the concepts of
      Floquet analysis can be applied to coherent lattice vibrations. This coupling
      leads to phonon-dressed quasi-particles imprinting specific signatures in the
      spectrum of the electronic structure. Such dressed electronic states can be
      detected by time- and angular-resolved photoelectron spectroscopy (ARPES)
      manifesting as sidebands to the equilibrium band structure. Taking graphene as a
      paradigmatic material with strong electron-phonon interaction and nontrivial
      topology, we show how the phonon-dressed states display an intricate sideband
      structure revealing the electron-phonon coupling at the Brillouin zone center and
      topological ordering of the Dirac bands. We demonstrate that if time-reversal
      symmetry is broken by the coherent lattice perturbations a topological phase
      transition can be induced. This work establishes that the recently demonstrated
      concept of light-induced nonequilibrium Floquet phases can also be applied when
      using coherent phonon modes for the dynamical control of material properties.

PMID- 29361224
TI  - Carbon Nanosheets Containing Discrete Co-Nx-By-C Active Sites for Efficient
      Oxygen Electrocatalysis and Rechargeable Zn-Air Batteries.
AB  - Structural and compositional engineering of atomic-scaled metal-N-C catalysts is
      important yet challenging in boosting their performance for the oxygen reduction
      reaction (ORR) and oxygen evolution reaction (OER). Here, boron (B)-doped Co-N-C
      active sites confined in hierarchical porous carbon sheets (denoted as Co-N,B
      CSs) were obtained by a soft template self-assembly pyrolysis method.
      Significantly, the introduced B element gives an electron-deficient site that can
      activate the electron transfer around the Co-N-C sites, strengthen the
      interaction with oxygenated species, and thus accelerate reaction kinetics in the
      4e- processed ORR and OER. As a result, the catalyst showed Pt-like ORR
      performance with a half-wave potential (E1/2) of 0.83 V versus (vs) RHE, a
      limiting current density of about 5.66 mA cm-2, and higher durability (almost no
      decay after 5000 cycles) than Pt/C catalysts. Moreover, a rechargeable Zn-air
      battery device comprising this Co-N,B-CSs catalyst shows superior performance
      with an open-circuit potential of ~1.4 V, a peak power density of ~100.4 mW cm-2,
      as well as excellent durability (128 cycles for 14 h of operation). DFT
      calculations further demonstrated that the coupling of Co-Nx active sites with B
      atoms prefers to adsorb an O2 molecule in side-on mode and accelerates ORR
      kinetics.

PMID- 29361225
TI  - Supramolecular Assembly of Photosystem II and Adenosine Triphosphate Synthase in
      Artificially Designed Honeycomb Multilayers for Photophosphorylation.
AB  - Plant thylakoids have a typical stacking structure, which is the site of
      photosynthesis, including light-harvesting, water-splitting, and adenosine
      triphosphate (ATP) production. This stacking structure plays a key role in
      exchange of substances with extremely high efficiency and minimum energy
      consumption through photosynthesis. Herein we report an artificially designed
      honeycomb multilayer for photophosphorylation. To mimic the natural thylakoid
      stacking structure, the multilayered photosystem II (PSII)-ATP synthase-liposome
      system is fabricated via layer-by-layer (LbL) assembly, allowing the three
      dimensional distributions of PSII and ATP synthase. Under light illumination,
      PSII splits water into protons and generates a proton gradient for ATP synthase
      to produce ATP. Moreover, it is found that the ATP production is extremely
      associated with the numbers of PSII layers. With such a multilayer structure
      assembled via LbL, one can better understand the mechanism of PSII and ATP
      synthase integrated in one system, mimicking the photosynthetic grana structure.
      On the other hand, such an assembled system can be considered to improve the
      photophosphorylation.

PMID- 29361226
TI  - Microstructure, Magnetic, and Magnetoresistance Properties of La0.7Sr0.3MnO3:CuO
      Nanocomposite Thin Films.
AB  - (La0.7Sr0.3MnO3)0.67:(CuO)0.33 (LSMO:CuO) nanocomposite thin films were deposited
      on SrTiO3 (001), LaAlO3 (001), and MgO (001) substrates by pulsed laser
      deposition, and their microstructure as well as magnetic and magnetoresistance
      properties were investigated. X-ray diffraction (XRD) and transmission electron
      microscopy (TEM) results show that LSMO:CuO films grow as highly textured self
      assembled vertically aligned nanocomposite (VAN), with a systematic domain
      structure and strain tuning effect based on the substrate type and laser
      deposition frequency. A record high low-field magnetoresistance (LFMR) value of
      ~80% has been achieved in LSMO:CuO grown on LaAlO3 (001) substrate under high
      frequency. Detailed analysis indicates that both the strain state and the phase
      boundary effect play a significant role in governing the overall LFMR behavior.

PMID- 29361227
TI  - Enhanced Adsorption of a Protein-Nanocarrier Complex onto Cell Membranes through
      a High Freeze Concentration by a Polyampholyte Cryoprotectant.
AB  - The transportation of biomolecules into cells is of great importance in tissue
      engineering and as stimulation for antitumor immune cells. Previous freezing
      strategies at ultracold temperatures (-80  degrees C) used for intracellular
      transportation exhibit certain limitations such as extended time requirements and
      harsh delivery system conditions. Thus, the need remains to develop simplified
      methods for safe nanomaterial delivery. Here, we demonstrated a unique strategy
      based on the ice-crystallization-induced freeze concentration for protein
      intracellular delivery in combination with a polyampholyte cryoprotectant. We
      found that upon sustained lowering of the temperature from -6 to -20  degrees C
      over a short duration, the adsorption of proteins onto the peripheral cell
      membrane was markedly increased through the facile ice-crystallization-induced
      freeze concentration. Furthermore, we proposed a freeze concentration factor
      (alpha) that depends on the freezing-point depression and is estimated from an
      analysis of the fraction of frozen water. Notably, the alpha values of the
      polyampholyte cryoprotectant were 8-fold higher than those of the currently used
      cryoprotectant dimethyl sulfoxide (DMSO) at particular temperatures of interest.
      Our results illustrate that the presence of a polyampholyte cryoprotectant
      significantly enhanced the adsorption of the protein/nanocarrier complex onto
      membranes compared to that obtained with DMSO because of the high freeze
      concentration. The present study demonstrated the direct relationship between
      freezing and the penetration of proteins across the periphery of the cell
      membrane by means of increased concentration during freezing. These results may
      be useful in providing a guideline for the intracellular delivery of
      biomacromolecules using ice-crystallization-induced continuous freezing combined
      with polyampholyte cryoprotectants.

PMID- 29361228
TI  - A DNA Tracer System for Hydrological Environment Investigations.
AB  - To monitor and manage hydrological pollution effectively, tracing sources of
      pollutants is of great importance and also is in urgent need. A variety of
      tracers have been developed such as isotopes, silica, bromide, and dyes; however,
      practical limitations of these traditional tracers still exist such as lack of
      multiplexed, multipoint tracing and interference of background noise. To overcome
      these limitations, a new tracing system based on DNA nanomaterials, namely DNA
      tracer, has already been developed. DNA tracers possess remarkable advantages
      including sufficient species, specificity, environmental friendly, stable
      migration, and high sensitivity as well as allowing for multipoints tracing. In
      this review article, we introduce the molecular design, synthesis, protection and
      signal readout strategies of DNA tracers, compare the advantages and
      disadvantages of DNA tracer with traditional tracers, and summarize the-state-of
      art applications in hydrological environment investigations. In the end, we
      provide our perspective on the future development of DNA tracers.

PMID- 29361229
TI  - Large Enhancement of Thermal Conductivity and Lorenz Number in Topological
      Insulator Thin Films.
AB  - Topological insulators (TI) have attracted extensive research effort due to their
      insulating bulk states but conducting surface states. However, investigation and
      understanding of thermal transport in topological insulators, particularly the
      effect of surface states, are lacking. In this work, we studied thickness
      dependent in-plane thermal and electrical conductivity of Bi2Te2Se TI thin films.
      A large enhancement in both thermal and electrical conductivity was observed for
      films with thicknesses below 20 nm, which is attributed to the surface states and
      bulk-insulating nature of these films. Moreover, a surface Lorenz number much
      larger than the Sommerfeld value was found. Systematic transport measurements
      indicated that the Fermi surface is located near the charge neutrality point
      (CNP) when the film thickness is below 20 nm. Possible reasons for the large
      Lorenz number include electrical and thermal current decoupling in the surface
      state Dirac fluid, and bipolar diffusion transport. A simple computational model
      indicates that the surface states and bipolar diffusion indeed can lead to
      enhanced electrical and thermal transport and a large Lorenz number.

PMID- 29361230
TI  - CDNs-STING Interaction Mechanism Investigations and Instructions on Design of CDN
      Derivatives.
AB  - Cyclic dinucleotides (CDNs) present thousand-fold differences of dissociation
      constants to STING, a pivotal protein in cytosolic dsDNA immunity. To understand
      how subtle chemical changes in CDNs lead to these substantial variances, a
      precise ranking of binding affinity is needed. However, the large size and
      flexibility of CDNs elevate the entropic effect and pose a challenge for this
      precise prediction. Therefore, in this paper, we developed a new protocol, a
      combination of selective-integrated tempering sampling of ligands and molecular
      docking, to take into account the entropic effects originating from extensive
      ligand configurational space and solvation on binding affinity evaluations. The
      calculated ranking orders of CDNs and CDN-derivatives to wild type STING and
      R232H mutant are in agreement with experimental measurements. Further molecular
      dynamics analysis revealed that the interaction between phosphonate groups and
      232R differentiates the binding affinities. The 2'-5' linked phosphonate groups
      have a larger tendency to form hydrogen bonds with 232R than those with 3'-5'
      linkages. Moreover, the new protocol identified structural features that enhanced
      CDNs-STING binding, such as anti-glycosidic bonds and large pro-R distances,
      which explains the high binding affinity of dithio-RpRp-2'3'-CDA to STING and is
      expected to provide valuable guidance in the lead-drug optimization.

PMID- 29361231
TI  - Hinge-Shift Mechanism Modulates Allosteric Regulations in Human Pin1.
AB  - Allostery, which is regulation from distant sites, plays a major role in biology.
      While traditional allostery is described in terms of conformational change upon
      ligand binding as an underlying principle, it is possible to have allosteric
      regulations without significant conformational change through modulating the
      conformational dynamics by altering the local effective elastic modulus of the
      protein upon ligand binding. Pin1 utilizes this dynamic allostery to regulate its
      function. It is a modular protein containing a WW domain and a larger peptidyl
      prolyl isomerase domain (PPIase) that isomerizes phosphoserine/threonine-proline
      (pS/TP) motifs. The WW domain serves as a docking module, whereas catalysis
      solely takes place within the PPIase domain. Here, we analyze the change in the
      dynamic flexibility profile of the PPIase domain upon ligand binding to the WW
      domain. Substrate binding to the WW domain induces the formation of a new rigid
      hinge site around the interface of the two domains and loosens the flexibility of
      a rigid site existing in the Apo form around the catalytic site. This hinge-shift
      mechanism enhances the dynamic coupling of the catalytic positions with the
      PPIase domain, where the rest of the domain can cooperatively respond to the
      local conformational changes around the catalytic site, leading to an increase in
      catalytic efficiency.

PMID- 29361232
TI  - Flaw-Containing Alumina Hollow Nanostructures Have Ultrahigh Fracture Strength To
      Be Incorporated into High-Efficiency GaN Light-Emitting Diodes.
AB  - In the present study, we found that alpha-alumina hollow nanoshell structure can
      exhibit an ultrahigh fracture strength even though it contains a significant
      number of nanopores. By systematically performing in situ mechanical testing and
      finite element simulations, we could measure that the fracture strength of an
      alpha-alumina hollow nanoshell structure is about four times higher than that of
      the conventional bulk size alpha-alumina. The high fracture strength of the alpha
      alumina hollow nanoshell structure can be explained in terms of conventional
      fracture mechanics, in that the position and size of the nanopores are the most
      critical factors determining the fracture strength, even at the nanoscales. More
      importantly, by deriving a fundamental understanding, we would be able to provide
      guidelines for the design of reliable ceramic nanostructures for advanced GaN
      light-emitting diodes (LEDs). To that end, we demonstrated how our ultrastrong
      alpha-alumina hollow nanoshell structures could be successfully incorporated into
      GaN LEDs, thereby greatly improving the luminous efficiency and output power of
      the LEDs by 2.2 times higher than that of conventional GaN LEDs.

PMID- 29361233
TI  - Manipulating the Architecture of Atomically Thin Transition Metal (Hydr)oxides
      for Enhanced Oxygen Evolution Catalysis.
AB  - Graphene-like nanomaterials have received tremendous research interest due to
      their atomic thickness and fascinating properties. Previous studies mainly focus
      on the modulation of their electronic structures, which undoubtedly optimizes the
      electronic properties, but is not the only determinant of performance in
      practical applications. Herein, we propose a generalized strategy to
      incrementally manipulate the architectures of several atomically thin transition
      metal (hydr)oxides, and study their effects on catalytic water oxidation. The
      results demonstrate the obvious superiority of a wrinkled nanosheet architecture
      in both catalytic activity and durability. For instance, wrinkled Ni(OH)2
      nanosheets display a low overpotential of 358.2 mV at 10 mA cm-2, a high current
      density of 187.2 mA cm-2 at 500 mV, a small Tafel slope of 54.4 mV dec-1, and
      excellent long-term durability with gradually optimized performance,
      significantly outperforming other nanosheet architectures and previously reported
      catalysts. The outstanding catalytic performance is mainly attributable to the 3D
      porous network structure constructed by wrinkled nanosheets, which not only
      provides sufficient contact between electrode materials and current collector,
      but also offers highly accessible channels for facile electrolyte diffusion and
      efficient O2 escape. Our study provides a perspective on improving the
      performance of graphene-like nanomaterials in a wide range of practical
      applications.

PMID- 29361234
TI  - Direct Synthesis of Hyperdoped Germanium Nanowires.
AB  - A low-temperature chemical vapor growth of Ge nanowires using Ga as seed material
      is demonstrated. The structural and chemical analysis reveals the homogeneous
      incorporation of ~3.5 at. % Ga in the Ge nanowires. The Ga-containing Ge
      nanowires behave like metallic conductors with a resistivity of about ~300
      MUOmegacm due to Ga hyperdoping with electronic contributions of one-third of the
      incorporated Ga atoms. This is the highest conduction value observed by in situ
      doping of group IV nanowires reported to date. This work demonstrates that Ga is
      both an efficient seed material at low temperatures for Ge nanowire growth and an
      effective dopant changing the semiconductor into a metal-like conductor.

PMID- 29361235
TI  - Intrapleural Fibrinolytic Therapy for Empyema and Pleural Loculation: Knowns and
      Unknowns.

PMID- 29361237
TI  - How Long Should We Be Vigilant after a Hospitalization for a Chronic Obstructive
      Pulmonary Disease Exacerbation?

PMID- 29361236
TI  - beta-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T
      Helper Type 2 Cells.
AB  - Allergic asthma is a complex inflammatory disease that leads to significant
      healthcare costs and reduction in quality of life. Although many cell types are
      implicated in the pathogenesis of asthma, CD4+ T-helper cell type 2 (Th2) cells
      are centrally involved. We previously reported that the asthma phenotype is
      virtually absent in ovalbumin-sensitized and -challenged mice that lack global
      expression of beta-arrestin (beta-arr)-2 and that CD4+ T cells from these mice
      displayed significantly reduced CCL22-mediated chemotaxis. Because CCL22-mediated
      activation of CCR4 plays a role in Th2 cell regulation in asthmatic inflammation,
      we hypothesized that CCR4-mediated migration of CD4+ Th2 cells to the lung in
      asthma may use beta-arr-dependent signaling. To test this hypothesis, we assessed
      the effect of various signaling inhibitors on CCL22-induced chemotaxis using in
      vitro-polarized primary CD4+ Th2 cells from beta-arr2-knockout and wild-type
      mice. Our results show, for the first time, that CCL22-induced, CCR4-mediated Th2
      cell chemotaxis is dependent, in part, on a beta-arr2-dependent signaling
      pathway. In addition, we show that this chemotactic signaling mechanism involves
      activation of P-p38 and Rho-associated protein kinase. These findings point to a
      proinflammatory role for beta-arr2-dependent signaling and support beta-arr2 as a
      novel therapeutic target in asthma.

PMID- 29361238
TI  - Digital Image Analyses on Whole-Lung Slides in Mouse Models of Acute Pneumonia.
AB  - Descriptive histopathology of mouse models of pneumonia is essential in assessing
      the outcome of infections, molecular manipulations, or therapies in the context
      of whole lungs. Quantitative comparisons between experimental groups, however,
      have been limited to laborious stereology or ill-defined scoring systems that
      depend on the subjectivity of a more or less experienced observer. Here, we
      introduce self-learning digital image analyses that allow us to transform optical
      information from whole mouse lung sections into statistically testable data. A
      pattern-recognition-based software and a nuclear count algorithm were adopted to
      quantify user-defined pathologies from whole slide scans of lungs infected with
      Streptococcus pneumoniae or influenza A virus compared with PBS-challenged lungs.
      The readout parameters "relative area affected" and "nuclear counts per area" are
      proposed as relevant criteria for the quantification of lesions from hematoxylin
      and eosin-stained sections, also allowing for the generation of a heat map of,
      for example, immune cell infiltrates with anatomical assignments across entire
      lung sections. Moreover, when combined with immunohistochemical labeling of
      marker proteins, both approaches are useful for the identification and counting
      of, for example, immune cell populations, as validated here by direct comparisons
      with flow cytometry data. The solutions can easily and flexibly be adjusted to
      specificities of different models or pathogens. Automated digital analyses of
      whole mouse lung sections may set a new standard for the user-defined, high
      throughput comparative quantification of histological and immunohistochemical
      images. Still, our algorithms established here are only a start, and need to be
      tested in additional studies and other applications in the future.

PMID- 29361240
TI  - Hurricane Maria: A Preventable Humanitarian and Health Care Crisis Unveiling the
      Puerto Rican Dilemma.

PMID- 29361239
TI  - New Method for Quantitation of Lipid Droplet Volume From Light Microscopic Images
      With an Application to Determination of PAT Protein Density on the Droplet
      Surface.
AB  - Determination of lipid droplet (LD) volume has depended on direct measurement of
      the diameter of individual LDs, which is not possible when LDs are small or
      closely apposed. To overcome this problem, we describe a new method in which a
      volume-fluorescence relationship is determined from automated analysis of
      calibration samples containing well-resolved LDs. This relationship is then used
      to estimate total cellular droplet volume in experimental samples, where the LDs
      need not be individually resolved, or to determine the volumes of individual LDs.
      We describe quantitatively the effects of various factors, including image noise,
      LD crowding, and variation in LD composition on the accuracy of this method. We
      then demonstrate this method by utilizing it to address a scientifically
      interesting question, to determine the density of green fluorescent protein (GFP)
      tagged Perilipin-Adipocyte-Tail (PAT) proteins on the LD surface. We find that
      PAT proteins cover only a minority of the LD surface, consistent with models in
      which they primarily serve as scaffolds for binding of regulatory proteins and
      enzymes, but inconsistent with models in which their major function is to
      sterically block access to the droplet surface.

PMID- 29361241
TI  - The SAGE Model of Social Psychological Research.
AB  - We propose a SAGE model for social psychological research. Encapsulated in our
      acronym is a proposal to have a synthetic approach to social psychological
      research, in which qualitative methods are augmentative to quantitative ones,
      qualitative methods can be generative of new experimental hypotheses, and
      qualitative methods can capture experiences that evade experimental reductionism.
      We remind social psychological researchers that psychology was founded in
      multiple methods of investigation at multiple levels of analysis. We discuss
      historical examples and our own research as contemporary examples of how a SAGE
      model can operate in part or as an integrated whole. The implications of our
      model are discussed.

PMID- 29361242
TI  - MR Imaging-based Estimation of Upper Motor Neuron Density in Patients with
      Amyotrophic Lateral Sclerosis: A Feasibility Study.
AB  - Purpose To determine if magnetic resonance (MR) imaging metrics can estimate
      primary motor cortex (PMC) motor neuron (MN) density in patients with amyotrophic
      lateral sclerosis (ALS). Materials and Methods Between 2012 and 2014, in situ
      brain MR imaging was performed in 11 patients with ALS (age range, 35-81 years;
      seven women and four men) soon after death (mean, 5.5 hours after death; range,
      3.2-9.6 hours). The brain was removed, right PMC (RPMC) was excised, and MN
      density was quantified. RPMC metrics (thickness, volume, and magnetization
      transfer ratio) were calculated from MR images. Regression modeling was used to
      estimate MN density by using RPMC and global MR imaging metrics (brain and tissue
      volumes); clinical variables were subsequently evaluated as additional
      estimators. Models were tested at in vivo MR imaging by using the same imaging
      protocol (six patients with ALS; age range, 54-66 years; three women and three
      men). Results RPMC mean MN density varied over a greater than threefold range
      across patients and was estimated by a linear function of normalized gray matter
      volume (adjusted R2 = 0.51; P = .008; <10% error in most patients). When
      considering only sporadic ALS, a linear function of normalized RPMC and white
      matter volumes estimated MN density (adjusted R2 = 0.98; P = .01; <10% error in
      all patients). In vivo data analyses detected decreases in MN density over time.
      Conclusion PMC mean MN density varies widely in end-stage ALS possibly because of
      disease heterogeneity. MN density can potentially be estimated by MR imaging
      metrics. (c) RSNA, 2018 Online supplemental material is available for this
      article.

PMID- 29361243
TI  - Emphysematous and Nonemphysematous Gas Trapping in Chronic Obstructive Pulmonary
      Disease: Quantitative CT Findings and Pulmonary Function.
AB  - Purpose To identify a prevalent computed tomography (CT) subtype in patients with
      chronic obstructive pulmonary disease (COPD) by separating emphysematous from
      nonemphysematous contributions to total gas trapping and to attempt to predict
      and grade the emphysematous gas trapping by using clinical and functional data.
      Materials and Methods Two-hundred and two consecutive eligible patients (159 men
      and 43 women; mean age, 70 years [age range, 41-85 years]) were prospectively
      studied. Pulmonary function and CT data were acquired by pulmonologists and
      radiologists. Noncontrast agent-enhanced thoracic CT scans were acquired at full
      inspiration and expiration, and were quantitatively analyzed by using two
      software programs. CT parameters were set as follows: 120 kVp; 200 mAs; rotation
      time, 0.5 second; pitch, 1.1; section thickness, 0.75 mm; and reconstruction
      kernels, b31f and b70f. Gas trapping obtained by difference of inspiratory and
      expiratory CT density thresholds (percentage area with CT attenuation values less
      than -950 HU at inspiration and percentage area with CT attenuation values less
      than -856 HU at expiration) was compared with that obtained by coregistration
      analysis. A logistic regression model on the basis of anthropometric and
      functional data was cross-validated and trained to classify patients with COPD
      according to the relative contribution of emphysema to total gas trapping, as
      assessed at CT. Results Gas trapping obtained by difference of inspiratory and
      expiratory CT density thresholds was highly correlated (r = 0.99) with that
      obtained by coregistration analysis. Four groups of patients were distinguished
      according to the prevalent CT subtype: prevalent emphysematous gas trapping,
      prevalent functional gas trapping, mixed severe, and mixed mild. The predictive
      model included predicted forced expiratory volume in 1 second/vital capacity,
      percentage of predicted forced expiratory volume in 1 second, percentage of
      diffusing capacity for carbon monoxide, and body mass index as emphysema
      regressors at CT, with 81% overall accuracy in classifying patients according to
      its extent. Conclusion The relative contribution of emphysematous and
      nonemphysematous gas trapping obtained by coregistration of inspiratory and
      expiratory CT scanning can be determined accurately by difference of CT
      inspiratory and expiratory density thresholds. CT extent of emphysema can be
      predicted with accuracy suitable for clinical purposes by pulmonary function data
      and body mass index. (c) RSNA, 2018 Online supplemental material is available for
      this article.

PMID- 29361244
TI  - Characterization of Prostate Cancer with Gleason Score of at Least 7 by Using
      Quantitative Multiparametric MR Imaging: Validation of a Computer-aided Diagnosis
      System in Patients Referred for Prostate Biopsy.
AB  - Purpose To determine the performance of a computer-aided diagnosis (CAD) system
      trained at characterizing cancers in the peripheral zone (PZ) with a Gleason
      score of at least 7 in patients referred for multiparametric magnetic resonance
      (MR) imaging before prostate biopsy. Materials and Methods Two institutional
      review board-approved prospective databases of patients who underwent
      multiparametric MR imaging before prostatectomy (database 1) or systematic and
      targeted biopsy (database 2) were retrospectively used. All patients gave
      informed consent for inclusion in the databases. A CAD combining the 10th
      percentile of the apparent diffusion coefficient and the time to peak of
      enhancement was trained to detect cancers in the PZ with a Gleason score of at
      least 7 in 106 patients from database 1. The CAD was tested in 129 different
      patients from database 2. All targeted lesions were prospectively scored at
      biopsy by using a five-level Likert score. The CAD scores were retrospectively
      calculated. Biopsy results were used as the reference standard. Areas under the
      receiver operating characteristic curves (AUCs) were computed for CAD and Likert
      scores by using binormal smoothing for per-lesion and per-lobe analyses, and a
      density function for per-patient analysis. Results The CAD outperformed the
      Likert score in the overall population and all subgroups, except in the
      transition zone. The difference was statistically significant for the overall
      population (AUC, 0.95 [95% confidence interval {CI}: 0.90, 0.98] vs 0.88 [95% CI:
      0.68, 0.96]; P = .02) at per-patient analysis, and for less-experienced
      radiologists (<1 year) at per-lesion (AUC, 0.90 [95% CI: 0.81, 0.95] vs 0.83 [95%
      CI: 0.73, 0.90]; P = .04) and per-lobe (AUC, 0.92 [95% CI: 0.80, 0.96] vs 0.84
      [95% CI: 0.72, 0.91]; P = .04) analysis. Conclusion The CAD outperformed the
      Likert score prospectively assigned at biopsy in characterizing cancers with a
      Gleason score of at least 7. (c) RSNA, 2018 Online supplemental material is
      available for this article.

PMID- 29361245
TI  - Brain Gliomas: Multicenter Standardized Assessment of Dynamic Contrast-enhanced
      and Dynamic Susceptibility Contrast MR Images.
AB  - Purpose To evaluate the feasibility of a standardized protocol for acquisition
      and analysis of dynamic contrast material-enhanced (DCE) and dynamic
      susceptibility contrast (DSC) magnetic resonance (MR) imaging in a multicenter
      clinical setting and to verify its accuracy in predicting glioma grade according
      to the new World Health Organization 2016 classification. Materials and Methods
      The local research ethics committees of all centers approved the study, and
      informed consent was obtained from patients. One hundred patients with glioma
      were prospectively examined at 3.0 T in seven centers that performed the same
      preoperative MR imaging protocol, including DCE and DSC sequences. Two
      independent readers identified the perfusion hotspots on maps of volume transfer
      constant (Ktrans), plasma (vp) and extravascular-extracellular space (ve)
      volumes, initial area under the concentration curve, and relative cerebral blood
      volume (rCBV). Differences in parameters between grades and molecular subtypes
      were assessed by using Kruskal-Wallis and Mann-Whitney U tests. Diagnostic
      accuracy was evaluated by using receiver operating characteristic curve analysis.
      Results The whole protocol was tolerated in all patients. Perfusion maps were
      successfully obtained in 94 patients. An excellent interreader reproducibility of
      DSC- and DCE-derived measures was found. Among DCE-derived parameters, vp and ve
      had the highest accuracy (are under the receiver operating characteristic curve
      [Az] = 0.847 and 0.853) for glioma grading. DSC-derived rCBV had the highest
      accuracy (Az = 0.894), but the difference was not statistically significant (P >
      .05). Among lower-grade gliomas, a moderate increase in both vp and rCBV was
      evident in isocitrate dehydrogenase wild-type tumors, although this was not
      significant (P > .05). Conclusion A standardized multicenter acquisition and
      analysis protocol of DCE and DSC MR imaging is feasible and highly reproducible.
      Both techniques showed a comparable, high diagnostic accuracy for grading
      gliomas. (c) RSNA, 2018 Online supplemental material is available for this
      article.

PMID- 29361246
TI  - Precision Matters in MR Imaging-targeted Prostate Biopsies: Evidence from a
      Prospective Study of Cognitive and Elastic Fusion Registration Transrectal
      Biopsies.
AB  - Purpose To measure the precision in placement of a biopsy needle in a magnetic
      resonance (MR) imaging-detected target with transrectal ultrasonography (US), to
      document the clinical relevance of precision, and to report on the precision of
      cognitive and software-based registrations. Materials and Methods This
      prospective study was approved by the institutional review board and performed
      between June 2013 and September 2013. Patients provided informed verbal consent.
      Two cores each were obtained with cognitive and fusion techniques in 88 patients
      with a Prostate Imaging Reporting and Data System version 1 score of at least 3.
      Precision was measured with Euclidian geometry by using the Digital Imaging and
      Communications in Medicine archives of the biopsy as the distance from the core
      to the center (dCC) and the distance from the core to the surface of the target
      modeled as a sphere. To address clustering of data from multiple cores in the
      same patients, analyses of precision focused on the best shot for a patient or a
      technique. The Welch unequal variance t test and Yates corrected chi2 test were
      used as appropriate. Results Mean precision was 2.5 mm (95% confidence interval:
      1.8 mm, 3.3 mm). Positive cores were closer to the center than were negative
      cores (dCC: 1.7 mm vs 3.1 mm, respectively; P = .025). More cancers were detected
      with on-target than off-target cores (33 of 71 cores [46.5%] vs three of 17 cores
      [17.6%]; P = .03). Cores obtained with the fusion technique achieved a higher
      precision than did cores obtained with the cognitive technique (dCC: 2.8 mm vs
      7.1 mm, respectively; P < .0001). Targeted cores demonstrated cancer in 44
      patients. Fewer cancers were detected with the cognitive technique than with the
      fusion technique (31 of 44 patients [70.5%] vs 40 of 44 patients [90.9%]; P =
      .03). Conclusion A deformable MR imaging/transrectal US image registration system
      achieved a higher precision and depicted cancer in more patients than did the
      cognitive freehand technique. (c) RSNA, 2018.

PMID- 29361247
TI  - Changes in Primary Care Health Care Utilization after Inclusion of Epidemiologic
      Data in Lumbar Spine MR Imaging Reports for Uncomplicated Low Back Pain.
AB  - Purpose To determine whether inclusion of an epidemiologic statement in radiology
      reports of lumbar magnetic resonance (MR) imaging influences downstream health
      care utilization in the primary care population. Materials and Methods Beginning
      July 1, 2013, a validated epidemiologic statement regarding prevalence of common
      findings in asymptomatic patients was included in all lumbar MR imaging reports
      at a tertiary academic medical center. Data were collected from July 1, 2012,
      through June 30, 2014, and retrospective analysis was completed in September
      2016. The electronic medical record was reviewed to capture health care
      utilization rates in patients for 1 year after index MR imaging. Of 4527 eligible
      adult patients with low back pain referred for lumbar spine MR imaging during the
      study period, 375 patients had their studies ordered by in-network primary care
      providers, did not have findings other than degenerative disease, and had at
      least one follow-up encounter within the system within 1 year of index MR
      imaging. In the before-and-after study design, a pre-statement-implementation
      cohort was compared with a post-statement-implementation cohort by using
      univariate and multivariate statistical models to evaluate treatment utilization
      rates in these groups. Results Patients in the statement group were 12% less
      likely to be referred to a spine specialist (137 of 187 [73%] vs 159 of 188
      [85%]; P = .007) and were 7% less likely to undergo repeat imaging (seven of 187
      [4%] vs 20 of 188 [11%]; P = .01) compared with patients in the nonstatement
      group. The intervention was not associated with any change in narcotic
      prescription (53 of 188 [28%] vs 54 of 187 [29%]; P = .88) or with the rate of
      low back surgery (24 of 188 [13%] vs 16 of 187 [9%]; P = .19). Conclusion In this
      study, inclusion of a simple epidemiologic statement in lumbar MR imaging reports
      was associated with decreased utilization in high-cost domains of low back pain
      management. (c) RSNA, 2018.

PMID- 29361249
TI  - Coramine and other analeptics.

PMID- 29361248
TI  - Characterization of FtsY, its interaction with Ffh, and proteomic identification
      of their potential substrates in Mycobacterium tuberculosis.
AB  - The universally conserved signal recognition particle (SRP) pathway that mediates
      co-translational targeting of membrane and secretory proteins is essential for
      eukaryotic and prokaryotic cells. The Mycobacterium tuberculosis SRP pathway
      consists of 2 proteins, Ffh and FtsY, and a 4.5S RNA molecule. Although the
      Escherichia coli SRP pathway is well studied, understanding of the M.
      tuberculosis SRP pathway components is very limited. In this study, we have
      overexpressed and characterized the M. tuberculosis SRP receptor (SR) FtsY as a
      GTP binding protein. Further, we established the direct protein-protein
      interaction between Ffh and FtsY. The Ffh-FtsY complex formation resulted in
      mutual stimulation of their GTP hydrolysis activity. We also attempted to
      biochemically characterize the SRP components by constructing the antisense gene
      knockdown strains of ffh and ftsY in M. tuberculosis. Loss of ffh and ftsY
      resulted in a decreased in vitro growth rate of the antisense ffh strain as
      compared with the antisense ftsY strain. Finally, 2-D gel electrophoresis of
      antisense depleted ffh and ftsY strains identified differential expression of 14
      proteins.

PMID- 29361250
TI  - Monitoring the nervous system: it's time to up our game.

PMID- 29361251
TI  - Feasibility and pilot studies: small steps before giant leaps.

PMID- 29361252
TI  - Basic and advanced echocardiographic evaluation of myocardial dysfunction in
      sepsis and septic shock.
AB  - Sepsis continues to be a leading cause of mortality and morbidity in the
      intensive care unit. Cardiovascular dysfunction in sepsis is associated with
      worse short- and long-term outcomes. Sepsis-related myocardial dysfunction is
      noted in 20%-65% of these patients and manifests as isolated or combined left or
      right ventricular systolic or diastolic dysfunction. Echocardiography is the most
      commonly used modality for the diagnosis of sepsis-related myocardial
      dysfunction. With the increasing use of ultrasonography in the intensive care
      unit, there is a renewed interest in sepsis-related myocardial dysfunction. This
      review summarises the current scope of literature focused on sepsis-related
      myocardial dysfunction and highlights the use of basic and advanced
      echocardiographic techniques for the diagnosis of sepsis-related myocardial
      dysfunction and the management of sepsis and septic shock.

PMID- 29361253
TI  - Anaesthetic issues in robotic-assisted minimally invasive surgery.
AB  - Over the past decade there has been an exponential increase in the number of
      robotic-assisted surgical procedures performed in Australia and internationally.
      Despite this growth, there are no level I or II studies examining the anaesthetic
      implications of these procedures. Available observational studies provide insight
      into the significant challenges for the anaesthetist. Most anaesthetic
      considerations overlap with those of non-robotic surgery. However, issues with
      limited patient access and extremes of positioning resulting in physiological
      disturbances and risk of injury are consistently demonstrated concerns specific
      to robotic-assisted procedures.

PMID- 29361254
TI  - High flow humidified nasal oxygen in pregnant women.
AB  - Failed airway management in the obstetric patient undergoing general anaesthesia
      is associated with major sequelae for the mother and/or fetus. Effective and
      adequate pre-oxygenation is an important safety strategy and a recommendation in
      all current major airway guidelines. Pre-oxygenation practice in the obstetric
      population may be suboptimal based on current literature. Recently, clinical
      applications for high flow nasal oxygen, also known as transnasal humidified
      rapid insufflation ventilatory exchange or THRIVE, are expanding in the non
      obstetric population and may have theoretical benefits if used for pre
      oxygenation and apnoeic oxygenation in the obstetric population. We review the
      current literature surrounding high flow nasal oxygen relevant to the pregnant
      woman. We also propose a basis for potential advantages and complications for its
      use in this context.

PMID- 29361255
TI  - Prevalence of augmented renal clearance and performance of glomerular filtration
      estimates in Indigenous Australian patients requiring intensive care admission.
AB  - Augmented renal clearance (ARC) refers to the enhanced renal excretion of
      circulating solute commonly demonstrated in numerous critically ill subgroups.
      This study aimed to describe the prevalence of ARC in critically ill Indigenous
      Australian patients and explore the accuracy of commonly employed mathematical
      estimates of glomerular filtration. We completed a single-centre, prospective,
      observational study in the intensive care unit (ICU), Alice Springs Hospital,
      Central Australia. Participants were critically ill adult Indigenous and non
      Indigenous Australian patients with a urinary catheter in situ. Exclusion
      criteria were anuria, pregnancy or the requirement for renal replacement therapy.
      Daily eight-hour measured creatinine clearances (CrCL<sub>m</sub>) were collected
      throughout the ICU stay. ARC was defined by a CrCL<sub>m</sub> >=130 ml/min/1.73
      m<sup>2</sup>. The Cockcroft-Gault and Chronic Kidney Disease Epidemiology
      Collaboration equations were also used to calculate mathematical estimates for
      comparison. In total, 131 patients were recruited (97 Indigenous, 34 non
      Indigenous) and 445 samples were collected. The median (range) CrCL<sub>m</sub>
      was 93.0 (5.14 to 205.2) and 90.4 (18.7 to 206.8) ml/min/1.73 m<sup>2</sup> in
      Indigenous and non-Indigenous patients, respectively. Thirty-one of 97 (32%)
      Indigenous patients manifested ARC, compared to 7 of 34 (21%) non-Indigenous
      patients (<i>P</i>=0.21). Younger age, major surgery, higher baseline renal
      function and an absence of diabetes were all associated with ARC. Both
      mathematical estimates manifest limited accuracy. ARC was prevalent in critically
      ill Indigenous patients, which places them at significant risk of underdosing
      with renally excreted drugs. CrCL<sub>m</sub> should be obtained wherever
      possible to ensure accurate dosing.

PMID- 29361256
TI  - The effect of sevoflurane on the transmural dispersion of repolarisation in
      patients with type 2 diabetes mellitus: a prospective observational study.
AB  - The 'torsadogenic' property of a drug is linked to its ability to increase the
      transmural dispersion of repolarisation, represented by the interval between the
      peak of, and the end of, the T-wave (Tp-e interval) in an electrocardiogram.
      Reports have consistently shown that sevoflurane does not increase the Tp-e
      interval. Type 2 diabetes is a risk factor for increased QTc (rate-corrected QT
      interval), QTcd (rate-corrected QTc dispersion: difference between the maximum
      and the minimum QTc interval), and Tp-e, as well as the rate-corrected Tp-e (Tp
      e/QTc ratio). The study aimed to ascertain whether sevoflurane increased the Tp-e
      interval and Tp-e/QTc ratio in patients with diabetes, thereby increasing their
      risk of torsades. We enrolled 35 female patients; 17 with type 2 diabetes and 18
      controls undergoing non-laparoscopic surgery under sevoflurane anaesthesia. The
      Tp-e interval, Tp-e/QTc ratio, QTc and QTcd were recorded after intubation, 5,
      10, 30 and 60 minutes into the anaesthetic, and were compared between the groups.
      No significant increase in the Tp-e interval or Tp-e/QTc was observed between or
      within the groups (a 13 ms increase was considered significant). In the control
      group, the QTc was significantly increased from baseline immediately after
      intubation (449 versus 414 ms, <i>P</i> <0.001); at 5 minutes (434 versus 414 ms,
      <i>P</i>=0.01); at 10 minutes (444 versus 414 ms, <i>P</i>=0.002); at 30 minutes
      (439 versus 414 ms, <i>P</i>=0.001) and at 60 minutes (442 versus 414 ms;
      <i>P</i> <0.001) (a 20 ms increase was considered significant). No significant
      increase in QTc was observed in the diabetic group. There were no between or
      within group differences observed for QTcd. Our findings suggest that sevoflurane
      does not have a significant predictable pro-arrhythmic effect in type 2 diabetic
      patients in the absence of other factors affecting ventricular repolarisation.

PMID- 29361257
TI  - The impact of alcohol-related admissions on resource use in critically ill
      patients from 2009 to 2015: an observational study.
AB  - Excessive alcohol use is associated with increased health care utilisation and
      increased mortality. This observational study sought to identify the proportion
      of patients admitted with a critical illness in which alcohol misuse contributed,
      and to examine the resource use for this group. We performed an observational
      retrospective database review of all admissions to the Alice Springs Hospital
      intensive care unit (ICU) between 1 January 2009 and 31 December 2015. The Alice
      Springs Hospital ICU is a ten-bed unit located in Central Australia, with
      approximately 600 admissions annually. The per capita consumption of alcohol in
      Central Australia is approximately 1.5 times the national average. The primary
      aim was to determine the proportion of admissions to intensive care in which
      alcohol misuse was identified as a contributing cause. Secondary aims examined
      resource utilisation including ICU and hospital length of stay, need for and
      duration of mechanical ventilation, and ICU re-admission. There were 3,768
      admissions involving 2,670 individual patients. Of these admissions 947 (25%)
      were associated with alcohol misuse. Admissions associated with alcohol were
      significantly more likely to require mechanical ventilation (30% versus 20%,
      <i>P</i> <0.01), and had a significantly longer ICU length of stay (2.1 versus
      1.9 days, <i>P</i> <0.05). The proportion of admissions in which alcohol misuse
      was implicated is amongst the highest in the published literature. The results of
      this study should drive further policy change directed at harm minimisation, and
      warrant more detailed epidemiological work at both a local and national level.

PMID- 29361258
TI  - The use of a simple three-level bronchoscopic assessment of inhalation injury to
      predict in-hospital mortality and duration of mechanical ventilation in patients
      with burns.
AB  - Major burn centres in Australia use bronchoscopy to assess severity of inhalation
      injuries despite limited evidence as to how best to classify severity of
      inhalational injury or its relationship to patient outcomes. All patients with
      burns who were admitted to the intensive care unit (ICU) at The Alfred Hospital
      between February 2010 and July 2014 and underwent bronchoscopy to assess
      inhalational injury, were reviewed. Age, total body surface area burnt, severity
      of illness indices and mechanisms of injury were extracted from medical histories
      and local ICU and burns registries. Inhalational injury was classified based on
      the Abbreviated Injury Score and then grouped into three categories (none/mild,
      moderate, or severe injury). Univariable and multivariable analyses were
      undertaken to examine the relationship between inhalational injury and outcomes
      (in-hospital mortality and duration of mechanical ventilation). One hundred and
      twenty-eight patients were classified as having none/mild inhalational injury, 81
      moderate, and 13 severe inhalation injury. Mortality in each group was 2.3%
      (3/128), 7.4% (6/81) and 30.7% (4/13) respectively. Median (interquartile range)
      duration of mechanical ventilation in each group was 26 (11-82) hours, 84 (32
      232) hours and 94 (21-146) hours respectively. After adjusting for age, total
      body surface area burnt and severity of illness, only the severe inhalation
      injury group was independently associated with increased mortality (odds ratio
      20.4 [95% confidence intervals {CI} 1.74 to 239.4], <i>P</i>=0.016). Moderate
      inhalation injury was independently associated with increased duration of
      ventilation (odds ratio 2.25 [95% CI 1.53 to 3.31], <i>P</i> <0.001), but not
      increased mortality. This study suggests that stratification of bronchoscopically
      assessed inhalational injury into three categories can provide useful prognostic
      information about duration of ventilation and mortality. Larger multicentre
      prospective studies are required to validate these findings.

PMID- 29361259
TI  - The establishment of an anaesthetist-managed intraoperative neurophysiological
      monitoring service and initial outcome data.
AB  - Neurophysiological monitoring has been recommended to reduce the risk of
      neurological damage during a wide variety of surgeries. While the concept of an
      anaesthesia-led intraoperative neurophysiological monitoring (IONM) service is
      not new, the quality of this service provision has not been studied. In this
      article, we present our experience with the establishment of this service, and
      the results of our audit of 302 cases monitored over the initial four years. Our
      results identified that an anaesthesia-led IONM service was able to achieve a
      reliable signal in 95.4% of cases and capture significant alerts in 15.6% of
      these cases with sensitivity, specificity, false positive and negative rates
      consistent with published data. Our results indicate an anaesthesia-led IONM
      service is effective in identifying patients at an increased risk of an adverse
      outcome.

PMID- 29361261
TI  - Predicting medical emergency team calls, cardiac arrest calls and re-admission
      after intensive care discharge: creation of a tool to identify at-risk patients.
AB  - We aimed to develop a predictive model for intensive care unit (ICU)-discharged
      patients at risk of post-ICU deterioration. We performed a retrospective, single
      centre cohort observational study by linking the hospital admission, patient
      pathology, ICU, and medical emergency team (MET) databases. All patients
      discharged from the Alfred Hospital ICU to wards between July 2012 and June 2014
      were included. The primary outcome was a composite endpoint of any MET call,
      cardiac arrest call or ICU re-admission. Multivariable logistic regression
      analysis was used to identify predictors of outcome and develop a risk
      stratification model. Four thousand, six hundred and thirty-two patients were
      included in the study. Of these, 878 (19%) patients had a MET call, 51 (1.1%)
      patients had cardiac arrest calls, 304 (6.5%) were re-admitted to ICU during the
      same hospital stay, and 964 (21%) had MET calls, cardiac arrest calls or ICU re
      admission. A discriminatory predictive model was developed (area under the
      receiver operating characteristic curve 0.72 [95% confidence intervals {CI} 0.70
      to 0.73]) which identified the following factors: increasing age (odds ratio [OR]
      1.012 [95% CI 1.007 to 1.017] <i>P</i> <0.001), ICU admission with subarachnoid
      haemorrhage (OR 2.26 [95% CI 1.22 to 4.16] <i>P</i>=0.009), admission to ICU from
      a ward (OR 1.67 [95% CI 1.31 to 2.13] <i>P</i> <0.001), Acute Physiology and
      Chronic Health Evaluation (APACHE) III score without the age component (OR 1.005
      [95% CI 1.001 to 1.010] <i>P</i>=0.025), tracheostomy on ICU discharge (OR 4.32
      [95% CI 2.9 to 6.42] <i>P</i> <0.001) and discharge to cardiothoracic (OR 2.43
      [95%CI 1.49 to 3.96] <i>P</i> <0.001) or oncology wards (OR 2.27 [95% CI 1.05 to
      4.89] <i>P</i>=0.036). Over the two-year period, 361 patients were identified as
      having a greater than 50% chance of having post-ICU deterioration. Factors are
      identifiable to predict patients at risk of post-ICU deterioration. This
      knowledge could be used to guide patient follow-up after ICU discharge, optimise
      healthcare resources, and improve patient outcomes and service delivery.

PMID- 29361260
TI  - Associations of fluid amount, type, and balance and acute kidney injury in
      patients undergoing major surgery.
AB  - Fluid administration has been reported to be associated with an increased risk of
      acute kidney injury (AKI). We assessed whether, after correction for fluid
      balance, amount and chloride content of fluids administered have an independent
      association with AKI. We performed an observational study in patients after major
      surgery assessing the independent association of AKI with volume, chloride
      content and fluid balance, after adjustment for Physiological and Operative
      Severity Score for enUmeration of Mortality and morbidity (POSSUM) score, age,
      elective versus emergency surgery, and duration of surgery. We studied 542
      consecutive patients undergoing major surgery. Of these, 476 patients had renal
      function tested as part of routine clinical care and 53 patients (11.1%)
      developed postoperative AKI. After adjustments, a 100 ml greater mean daily fluid
      balance was artificially associated with a 5% decrease in the instantaneous
      hazard of AKI: adjusted Hazard Ratio (aHR) 0.951, 95% confidence intervals (CI)
      0.935 to 0.967, <i>P</i> <0.001. However, after adjustment for the proportion of
      chloride-restrictive fluids, mean daily fluid amounts and balances, POSSUM
      morbidity, age, duration and emergency status of surgery, and the confounding
      effect of fluid balance, every 5% increase in the proportion of chloride-liberal
      fluid administered was associated with an 8% increase in the instantaneous hazard
      of AKI (aHR 1.079, 95% CI 1.032 to 1.128, <i>P</i>=0.001), and a 100 ml increase
      in mean daily fluid amount given was associated with a 6% increase in the
      instantaneous hazard of AKI (aHR 1.061, 95% CI 1.047 to 1.075, <i>P</i> <0.001).
      After adjusting for key risk factors and for the confounding effect of fluid
      balance, greater fluid administration and greater administration of chloride-rich
      fluid were associated with greater risk of AKI.

PMID- 29361262
TI  - Cannula cricothyroidotomy and rescue oxygenation with the Rapid-O2TM oxygen
      insufflation device in the management of a can't intubate/can't oxygenate
      scenario.
AB  - We describe the successful use of cannula cricothyroidotomy and the Rapid-O2TM
      oxygen insufflation device (Meditech Systems Ltd, Dorset, UK) for rescue of a
      can't intubate/can't oxygenate (CICO) scenario in a patient with severe airway
      haemorrhage post-debridement of laryngeal amyloidosis. This case highlights the
      practical utility of a cannula technique for CICO rescue when appropriate
      equipment is used and when institutional measures are taken to prepare for this
      rare anaesthetic crisis.

PMID- 29361263
TI  - Ongoing design concerns of portable oxygen cylinders.

PMID- 29361264
TI  - Fluid bolus therapy for the ward treatment of oliguria after major abdominal
      surgery.

PMID- 29361265
TI  - Intraoperative use of adjuvants for opioid sparing: a cross-sectional survey of
      anaesthetists in teaching hospitals in South Australia.

PMID- 29361266
TI  - Major haemorrhage associated with the Flexi-Seal(r) Fecal Management System.

PMID- 29361267
TI  - A general framework for sensor-based human activity recognition.
AB  - Today's wearable devices like smartphones, smartwatches and intelligent glasses
      collect a large amount of data from their built-in sensors like accelerometers
      and gyroscopes. These data can be used to identify a person's current activity
      and in turn can be utilised for applications in the field of personal fitness
      assistants or elderly care. However, developing such systems is subject to
      certain restrictions: (i) since more and more new sensors will be available in
      the future, activity recognition systems should be able to integrate these new
      sensors with a small amount of manual effort and (ii) such systems should avoid
      high acquisition costs for computational power. We propose a general framework
      that achieves an effective data integration based on the following two
      characteristics: Firstly, a smartphone is used to gather and temporally store
      data from different sensors and transfer these data to a central server. Thus,
      various sensors can be integrated into the system as long as they have
      programming interfaces to communicate with the smartphone. The second
      characteristic is a codebook-based feature learning approach that can encode data
      from each sensor into an effective feature vector only by tuning a few intuitive
      parameters. In the experiments, the framework is realised as a real-time activity
      recognition system that integrates eight sensors from a smartphone, smartwatch
      and smartglasses, and its effectiveness is validated from different perspectives
      such as accuracies, sensor combinations and sampling rates.

PMID- 29361268
TI  - Gamma Ventral Capsulotomy in Intractable Obsessive-Compulsive Disorder.
AB  - BACKGROUND: Despite the development of effective pharmacologic and cognitive
      behavioral treatments for obsessive-compulsive disorder (OCD), some patients
      continue to be treatment-refractory and severely impaired. Fiber tracts
      connecting orbitofrontal and dorsal anterior cingulate cortex with subcortical
      nuclei have been the target of neurosurgical lesions as well as deep brain
      stimulation in these patients. We report on the safety and efficacy of ventral
      gamma capsulotomy for patients with intractable OCD. METHODS: Fifty-five patients
      with severely disabling, treatment-refractory OCD received bilateral lesions in
      the ventral portion of the anterior limb of the internal capsule over a 20-year
      period using the Leksell Gamma Knife. The patients were prospectively followed
      over 3 years with psychiatric, neurologic, and neuropsychological assessments of
      safety and efficacy, as well as structural neuroimaging. RESULTS: Thirty-one of
      55 patients (56%) had an improvement in the primary efficacy measure, the Yale
      Brown Obsessive Compulsive Scale, of >=35% over the 3-year follow-up period.
      Patients had significant improvements in depression, anxiety, quality of life,
      and global functioning. Patients tolerated the procedure well without significant
      acute adverse events. Five patients (9%) developed transient edema that required
      short courses of dexamethasone. Three patients (5%) developed cysts at long-term
      follow-up, 1 of whom developed radionecrosis resulting in an ongoing minimally
      conscious state. CONCLUSIONS: Gamma Knife ventral capsulotomy is an effective
      radiosurgical procedure for many treatment-refractory OCD patients. A minority of
      patients developed cysts at long-term follow-up, 1 of whom had permanent
      neurological sequelae.

PMID- 29361269
TI  - [The role of pharmacist in a telemedicine collaboration in hemodialysis: Water
      bacteriological quality monitoring].
AB  - OBJECTIVES: In French health centers, the pharmacist is responsible for the
      quality of hemodialysis fluids. In an insular hospital, it is difficult to make
      bacteriological controls because of the lack of an environmental laboratory.
      Alternative choices of methods must be seek to facilitate water control and
      ensure the security of hemodialysis for patients. Controlling the microbiological
      risk is an essential condition for the good operation of a telemedicine
      partnership in dialysis. METHODS: A review of the different methods that has been
      tried is presented. The hospital has experienced since 2014 a microorganism
      detection test by ATPmetry. An overview of the results is discussed. RESULTS: The
      usability of this technique allows quarterly controls on the water treated by
      reverse osmosis and on fluids after one and two ultrafiltrations from every
      generator. Cases of non-compliance were due to false positives, which were
      squashed by verification control in 50% of the cases, and the other non
      compliances were fixed by corrective actions. CONCLUSIONS: The ATPmetry technique
      permits the collection of rapid results and verification of the effectiveness of
      the corrective actions immediately after their implementation. This method has
      been undertaken in a routine use instead of the reference technique
      (bacteriological cultures). Assuming a constant vigilance in the quality of
      dialysis fluids that is a part of a quality approach, the pharmacist is at the
      heart of the telemedicine partnership developed in hemodialysis on the island.

PMID- 29361270
TI  - Update on SAMS: Statin-associated muscle symptoms.

PMID- 29361271
TI  - Nonatherosclerotic vascular causes of acute abdominal pain.
AB  - BACKGROUND: To examine the epidemiology, treatments, and outcomes of acute
      symptomatic non-atherosclerotic mesenteric vascular disease. METHODS: Subjects
      were reviewed over a six year period. Categories included embolism (EM),
      dissection (DI), and aneurysm (AN). Presentation, demographics, treatment and
      outcomes were compared. RESULTS: 46 patients were identified (EM:20, AN:15,
      DI:11). Age at presentation differed (EM: 66.3, AN 62.4, DI 54.6, p < .05). EM
      more likely affected the superior mesenteric artery (EM80%, AN20%, DI45%, p =
      .002), DI hepatic artery (EM20%, AN13%, DI55%, p < .05), and AN mesenteric
      branches (EM5%, AN47%, DI0%; p = .001). EM more likely had history of arrhythmia
      (EM40%, AN7%, DI0%, p,0.05) and diarrhea (EM30%, AN7%, DI0%, p < .05). Treatment
      was most often surgical in EM (EM85%, AN33%, DI9%, p < .001), endovascular in AN
      (EM5%, AN40%, DI 9%, p < .02), and conservative in DI (EM15%, AN 33%, DI82%, p <
      .05). In hospital mortality was infrequent (EM10%, AN7%, DI0%, p = ns). Mean
      hospital length of stay differed by mechanism (EM13.6days, AN9.2, DI2.3, p =
      .005). Median follow up was 61 months. Survival at 1, 3 and 5 years for emboli
      was 75%, 70% and 59%, for aneurysms 93%, 86%, and 77%, and for dissections 100%
      at all time points (p = .043 log rank). CONCLUSIONS: Patients with EM, AN, and DI
      differ in age, anatomic distribution and method of treatment. The etiology
      significantly affects long term survival.

PMID- 29361272
TI  - HIV-Associated Psoriasis.
AB  - Human immunodeficiency virus (HIV) prevalence is increasing worldwide as people
      on antiretroviral therapy are living longer. These patients are often susceptible
      to debilitating inflammatory disorders that are frequently refractory to standard
      treatment. Psoriasis is a systemic inflammatory disorder, associated with both
      physical and psychological burden, and can be the presenting feature of HIV
      infection. In this population, psoriasis tends to be more severe, to have
      atypical presentations and higher failure rates with the usual prescribed
      treatments. Management of moderate and severe HIV-associated psoriasis is
      challenging. Systemic conventional and biologic agents may be considered, but
      patients should be carefully followed up for potential adverse events, like
      opportunist infections, and regular monitoring of CD4 counts and HIV viral loads.

PMID- 29361273
TI  - Multiple Acral Syringomas.

PMID- 29361274
TI  - Quantifying bone structure, micro-architecture, and pathophysiology with MRI.
AB  - The radiology of bone has been transformed by magnetic resonance imaging, which
      has the ability to interrogate bone's complex architecture and physiology. New
      techniques provide information about both the macrostructure and microstructure
      of bone ranging from micrometre detail to the whole skeleton. Furthermore
      functional information about bone physiology can be used to detect disease early
      before structural changes occur. The future of bone imaging is in quantifying the
      anatomical and functional information to diagnose and monitor disease more
      precisely. This review explores the state of the art in quantitative MRI bone
      imaging.

PMID- 29361275
TI  - Individuals with varus thrust do not increase knee adduction when running with
      body borne load.
AB  - Osteoarthritis (OA) is a common occupational hazard for service members. This
      study quantified how body borne load impacts knee biomechanics for participants
      who do and do not present varus thrust (range of knee adduction motion exhibited
      from heel strike to mid-stance (0-51%)) during over-ground running. Eighteen (9
      varus thrust and 9 control) military personnel had knee biomechanics recorded
      when running with three load conditions (light, ~6 kg, medium, 15% BW, and heavy,
      30% BW). Subject-based means for knee biomechanics were calculated and submitted
      to a RM ANOVA to test the main effects and possible interactions between load and
      varus thrust group. The varus thrust group exhibited greater varus thrust (p =
      .001) and peak stance (PS, 0-100%) knee adduction (p = .009) posture compared to
      the control group with the light load, but not for the medium (p = .741 and p =
      .825) or heavy loads (p = .142 and p = .429). With the heavy load, varus thrust
      group reduced varus thrust (p = .023), whereas, the control group increased varus
      thrust (p = .037) compared to the light load, and increased PS knee adduction
      moment compared to light (p = .006) and medium loads (p = .031). The varus thrust
      group, however, exhibited no significant difference in knee adduction moment
      between any load (p = .174). With the addition of body borne load, varus thrust
      participants exhibited a significant reduction in knee biomechanics related to
      OA; whereas, control participants adopted knee biomechanics, including greater
      varus thrust and knee adduction moment, related to the development of OA.

PMID- 29361277
TI  - Painless Scrotal Hematoma as a Sign of Adrenal Hemorrhage in Newborns.

PMID- 29361276
TI  - Characterizing viscoelastic properties of breast cancer tissue in a mouse model
      using indentation.
AB  - Breast cancer is one of the leading cancer forms affecting females worldwide.
      Characterizing the mechanical properties of breast cancer tissue is important for
      diagnosis and uncovering the mechanobiology mechanism. Although most of the
      studies were based on human cancer tissue, an animal model is still describable
      for preclinical analysis. Using a custom-build indentation device, we measured
      the viscoelastic properties of breast cancer tissue from 4T1 and SKBR3 cell
      lines. A total of 7 samples were tested for each cancer tissue using a mouse
      model. We observed that a viscoelastic model with 2-term Prony series could best
      describe the ramp and stress relaxation of the tissue. For long-term responses,
      the SKBR3 tissues were stiffer in the strain levels of 4-10%, while no
      significant differences were found for the instantaneous elastic modulus. We also
      found tissues from both cell lines appeared to be strain-independent for the
      instantaneous elastic modulus and for the long-term elastic modulus in the strain
      level of 4-10%. In addition, by inspecting the cellular morphological structure
      of the two tissues, we found that SKBR3 tissues had a larger volume ratio of
      nuclei and a smaller volume ratio of extracellular matrix (ECM). Compared with
      prior cellular mechanics studies, our results indicated that ECM could contribute
      to the stiffening the tissue-level behavior. The viscoelastic characterization of
      the breast cancer tissue contributed to the scarce animal model data and provided
      support for the linear viscoelastic model used for in vivo elastography studies.
      Results also supplied helpful information for modeling of the breast cancer
      tissue in the tissue and cellular levels.

PMID- 29361278
TI  - Febrile infants and lumbar punctures: unravelling the evidence.

PMID- 29361279
TI  - Initial primary spontaneous pneumothorax in children and adolescents: Operate or
      wait?
AB  - PURPOSE: The management of primary spontaneous pneumothorax (PSP) in the
      pediatric population is not standardized. The purpose of this study was to
      understand the management options for a first episode of PSP in children and
      adolescents, and their associated outcomes. METHODS: A retrospective study was
      conducted for patients 5-20 years old with a diagnosis of PSP at a large academic
      children's hospital between 2002 and 2014. Patient data were reviewed for each
      case. Management and outcomes were analyzed and compared between groups. RESULTS:
      Eighty patients met all inclusion criteria. Overall recurrence rate was 40% with
      86% occurring within 12 months of the initial PSP. Patients with recurrent PSP
      were significantly taller. Size of pneumothorax based on initial chest x-ray was
      comparable between recurrent and nonrecurrent groups. A negative CT scan for
      subpleural blebs did not predict recurrence. Patients undergoing thoracoscopic
      blebectomy and mechanical pleurodesis at initial presentation had significantly
      lower recurrence rate compared to patients who underwent nonoperative management
      (operative group 14%, nonoperative group 45%; p=0.0373). CONCLUSIONS: Recurrence
      following nonoperative management was high with the majority occurring within a
      year and requiring readmission. These findings support offering surgery to
      families as a potential initial management option. LEVEL OF EVIDENCE: 3b/4 -
      retrospective series or case control study, single institution, very limited
      population.

PMID- 29361280
TI  - Ballast water management system: Assessment of chemical quality status of several
      ports in Adriatic Sea.
AB  - Oxidant treatment of ballast water (BW) is commonly used in BW systems in order
      to minimize the transport of alien species. The release of disinfection by
      products (DBPs) associated to the treatment of BW and cross-contamination of
      butyltin (BT) compounds through BW discharge is a topic of environmental concern.
      A chemical port baseline survey has been conducted in seven ports of the Adriatic
      Sea. Analysis have been performed on transplanted mussels, surface sediment,
      seawater, BW. Results showed an evidence of BT contamination, particularly in
      sediments, probably related to their illegal usage or to intensive shipping
      activities. Therefore, BW may act as a vector and contribute to re-buildup of BT
      contamination in the coastal regions. A baseline set of data concerning DBPs is
      provided, showing the preferential distribution of these compounds in the marine
      environment that will be useful for future considerations on monitoring and
      assessment of chemical contamination associated with BW.

PMID- 29361281
TI  - A high-throughput headspace gas chromatographic technique for the determination
      of nitrite content in water samples.
AB  - This paper reports on a high-throughput headspace gas chromatographic method (HS
      GC) for the determination of nitrite content in water sample, based on GC
      measurement of cyclohexene produced from the reaction between nitrite and
      cyclamate in a closed vial. The method has a relative standard deviation of
      <3.5%; The differences between the results of the nitrite measurements obtained
      by this method and those of a reference method were less than 5.8% and the
      recoveries of the method were in the range of 94.8-102% (for a spiked nitrite
      content range from 0.002 to 0.03 mg/L). The limit of detection of the method was
      0.46 MUg L-1. Due to an overlapping mode in the headspace auto-sampler system,
      the method can provide an automated and high-throughput nitrite analysis for the
      surface water samples. In short, the present HS-GC method is simple, accurate,
      and sensitive, and it is very suitable to be used in the batch sample testing.

PMID- 29361283
TI  - Cerebral vasomotor reactivity predicts the development of acute stroke in
      patients with internal carotid artery stenosis.
AB  - OBJECTIVE: To investigate the relationship between cerebral vasomotor reactivity
      (VMR) and acute stroke in patients with internal carotid artery stenosis.
      METHODS: 54 patients with internal carotid artery stenosis were enrolled. VMR was
      calculated by transcranial Doppler monitoring of the velocity of blood flow. 3
      Dimensional dynamic contrast enhanced magnetic resonance angiography was used to
      detect stenosis, and diffusion weighted imaging was used to detect infarction.
      RESULTS: VMR value was significantly lower in patients with carotid artery
      stenosis than in control group (T=3.112, P=0.002), and significantly lower in
      patients with aortic atherosclerotic stroke than in non-infarct group (T=10.930,
      P=0.000). However, VMR value was significantly higher in patients with new-onset
      small-artery occlusion stroke than in non-infarction group (T=-2.538, P=0.013).
      Scatter plots showed that aortic atherosclerotic stroke occurred mainly in
      patients with severe internal carotid artery stenosis, and VMR value in cerebral
      artery significantly decreased. CONCLUSION: Decreased VMR value is an important
      prognostic factor for the occurrence of aortic atherosclerotic stroke, and can be
      used as a reference for preoperative hemodynamic evaluation in patients with
      internal carotid artery stenosis.

PMID- 29361282
TI  - A rapid quantitative assay for juvenile hormones and intermediates in the
      biosynthetic pathway using gas chromatography tandem mass spectrometry.
AB  - A method for rapid quantitation of insect juvenile hormones (JH) and
      intermediates in the biosynthetic pathway, both in vitro and in vivo (hemolymph
      and whole body), has been developed using GC-MS/MS. This method is as simple as
      the radiochemical assay (RCA), the most commonly used method for measurement of
      JH biosynthesis in vitro, without need for further purification and
      derivatization, or radioactive precursors or ligands. It shows high sensitivity,
      accuracy and reproducibility. Linear responses were obtained the range of 1-800
      ng/mL (approximately 4-3000 nM). Recovery efficiencies for farnesol, farnesal,
      methyl farnesoate and JH III were approximately 100% in vitro and over 90% in
      vivo, with excellent reproducibility at three different spike levels. Titer of JH
      III in the hemolymph was relatively low at day 0 (adult female emergence) (79.68
      +/- 5.03 ng/mL) but increased to a maximum of 1717 ng/mL five days later. In
      whole body, JH III quantity reached a maximum on day 4 (845.5 +/- 87.9 ng/g) and
      day 5 (679.7 +/- 164.6 ng/g) and declined rapidly thereafter. It is in agreement
      with the hemolymph titer changes and biosynthetic rate of JH in vitro. Comparison
      with the results of inhibition of JH biosynthesis by two known inhibitors
      (allatostatin (AST) mimic H17 and pitavastatin) using RCA and GC-MS/MS, showed
      that there was little difference between the two methods In contrast to other
      methods, the present method with GC-MS/MS can be used to elucidate the mechanism
      of inhibition by inhibitors of JH biosynthesis without any derivatization and
      purification. This method is applicable to screening of JH inhibitors and the
      study of inhibitory mechanisms with high sensitivity and accurate quantification.
      It may also be useful for the determination of JH titer in other Arthropods.

PMID- 29361284
TI  - Intraoperative 3 tesla magnetic resonance imaging: our experience in tumors.
AB  - OBJECTIVE: To report our experience in the use of 3 tesla intraoperative magnetic
      resonance imaging (MRI) in neurosurgical procedures for tumors, and to evaluate
      the criteria for increasing the extension of resection. MATERIAL AND METHODS:
      This retrospective study included all consecutive intraoperative MRI studies done
      for neuro-oncologic disease in the first 13 months after the implementation of
      the technique. We registered possible immediate complications, the presence of
      tumor remnants, and whether the results of the intraoperative MRI study changed
      the surgical management. We recorded the duration of surgery in all cases.
      RESULTS: The most common tumor was recurrent glioblastoma, followed by primary
      glioblastoma and metastases. Complete resection was achieved in 28%, and tumor
      remnants remained in 72%. Intraoperative MRI enabled neurosurgeons to improve the
      extent of the resection in 85% of cases. The mean duration of surgery was 390+/
      122minutes. CONCLUSION: Intraoperative MRI using a strong magnetic field (3
      teslas) is a valid new technique that enables precise study of the tumor
      resection to determine whether the resection can be extended without damaging
      eloquent zones. Although the use of MRI increases the duration of surgery, the
      time required decreases as the team becomes more familiar with the technique.

PMID- 29361285
TI  - Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis
      (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study).
AB  - Observational studies indicate that low-density lipoprotein (LDL) cholesterol
      acts as a primary contributor to an active process leading to aortic stenosis
      (AS) development. However, randomized clinical trials have failed to demonstrate
      an effect of lipid lowering on impeding AS progression. This study explored if
      pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering
      therapy. The study goal was evaluated in the analysis of surviving patients with
      baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of
      1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak
      aortic jet velocity was the primary effect estimate. Linear mixed model analysis
      adjusted by baseline peak jet velocity and pretreatment LDL levels was used to
      assess effect modifications of treatment. Data were available in 1,579 (84%)
      patients. In adjusted analyses, lower baseline peak aortic jet velocity and
      higher pretreatment LDL levels increased the effect of randomized treatment (p =
      0.04 for interaction). As such, treatment impeded progression of AS in the
      highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per
      year slower progression vs placebo in peak aortic jet velocity, 95% confidence
      interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL.
      Conversely, among patients with moderate AS, there was no detectable effect of
      treatment in any of the pretreatment LDL quartiles (all p >=0.14). In conclusion,
      in a non-prespecified post hoc analysis, the efficacy of lipid-lowering therapy
      on impeding AS progression increased with higher pretreatment LDL and lower peak
      aortic jet velocity (SEAS study: NCT00092677).

PMID- 29361286
TI  - Gender-Specific Differences in All-Cause Mortality Between Incomplete and
      Complete Revascularization in Patients With ST-Elevation Myocardial Infarction
      and Multi-Vessel Coronary Artery Disease.
AB  - The best revascularization strategy (complete vs incomplete revascularization) in
      patients with ST-elevation myocardial infarction (STEMI) is still debated. The
      interaction between gender and revascularization strategy in patients with STEMI
      on all-cause mortality is uncertain. The aim of the present study was to evaluate
      gender-specific difference in all-cause mortality between incomplete and complete
      revascularization in patients with STEMI and multi-vessel coronary artery
      disease. The study population consisted of 375 men and 115 women with a first
      STEMI and multi-vessel coronary artery disease without cardiogenic shock at
      admission or left main stenosis. The 30-day and 5-year all-cause mortality was
      examined in patients categorized according to gender and revascularization
      strategy (incomplete and complete revascularization). Within the first 30 days,
      men and women with incomplete revascularization were associated with higher
      mortality rates compared with men with complete revascularization. However, the
      gender-strategy interaction variable was not independently associated with 30-day
      mortality after STEMI when corrected for baseline characteristics and
      angiographic features. Within the survivors of the first 30 days, men with
      incomplete revascularization (compared with men with complete revascularization)
      were independently associated with all-cause mortality during 5 years of follow
      up (hazard ratios 3.07, 95% confidence interval 1.24;7.61, p = 0.016). In
      contrast, women with incomplete revascularization were not independently
      associated with 5-year all-cause mortality (hazard ratios 0.60, 95% confidence
      interval 0.14;2.51, p = 0.48). In conclusion, no gender-strategy differences
      occurred in all-cause mortality within 30 days after STEMI. However, in the
      survivors of the first 30 days, incomplete revascularization in men was
      independently associated with all-cause mortality during 5-year follow-up, but
      this was not the case in women.

PMID- 29361287
TI  - Coronary Computed Tomography-Derived Fractional Flow Reserve Assessment-A
      Gatekeeper in Intermediate Stenoses.

PMID- 29361288
TI  - Comparisons of the Framingham and Pooled Cohort Equation Risk Scores for
      Detecting Subclinical Vascular Disease in Blacks Versus Whites.
AB  - The pooled cohort Atherosclerotic Cardiovascular Disease (ASCVD) risk calculator
      is designed to improve cardiovascular risk estimation compared with the
      Framingham Risk Score, particularly in blacks. Although the ASCVD risk score
      better predicts mortality and incident cardiovascular disease in blacks, less is
      known about its performance for subclinical vascular disease measures, including
      arterial stiffness and carotid intima-media thickness. We sought to determine if
      the ASCVD risk score better identifies subclinical vascular disease in blacks
      compared with the Framingham risk score. We calculated both the Framingham and
      ASCVD cohort risk scores in 1,231 subjects (mean age 53 years, 59% female, 37%
      black) without known cardiovascular disease and measured the extent of arterial
      stiffness, as determined by pulse wave velocity (PWV), central pulse pressure
      (CPP), and central augmentation index (CAIx), and subclinical atherosclerosis, as
      determined by carotid-IMT (C-IMT). Compared with whites, blacks had higher CAIx
      (23.9 +/- 10.2 vs 22.1 +/- 9.6%, p = 0.004), CPP (36.4 +/- 10.5 vs 34.9 +/- 9.8
      mmHg, p = 0.014), PWV (7.6 +/- 1.5 vs 7.3 +/- 1.3 m/s, p = 0.004), and C-IMT
      (0.67 +/- 0.10 vs 0.65 +/- 0.10 mm, p = 0.005). In a multivariable analysis
      including race and Framingham risk score, race remained an independent predictor
      of all measures of subclinical vascular disease; however, models with race and
      the ASCVD risk score showed that race was not an independent predictor of
      subclinical vascular disease. In conclusion, greater subclinical vascular disease
      in blacks was not estimated by the Framingham risk score. The new ASCVD risk
      score provided a better estimate of racial differences in vascular function and
      structure.

PMID- 29361289
TI  - Relation of Baseline Hemoglobin Level to In-Hospital Outcomes in Patients Who
      Undergo Percutaneous Coronary Intervention (from a Japanese Multicenter
      Registry).
AB  - Scarce data exist regarding the relation between baseline hemoglobin and in
      hospital outcomes after percutaneous coronary intervention (PCI). We studied
      13,010 cases of PCI in a Japanese multicenter registry from 2008 to 2016.
      Patients were divided into 5 groups according to 2-g/dl increments in their
      preprocedural hemoglobin (from <10 to >16 g/dl). Patients with lower hemoglobin
      levels were older and had higher proportions of females and co-morbidities,
      including diabetes mellitus and renal failure, than those with higher hemoglobin
      levels. In-hospital complications were observed more frequently in patients with
      lower than higher levels. After adjustment, baseline hemoglobin was inversely
      associated with total procedural complications (odds ratio [OR] 0.87, 95%
      confidence interval [CI] 0.84 to 0.90, p <0.001), in-hospital mortality (OR 0.82,
      95% CI 0.77 to 0.87, p <0.001), and bleeding complications (OR 0.93, 95% CI 0.88
      to 0.98, p = 0.007). Categorically, reverse J-shaped curvilinear correlations
      were present between baseline hemoglobin and in-hospital adverse outcomes. When
      the reference group comprised patients with a baseline hemoglobin of 12 to 14
      g/dl, patients within the lowest hemoglobin levels (<10 g/dl) were at the highest
      risk of total procedural complications (OR 2.57, 95% CI 2.07 to 3.17, p <0.001),
      in-hospital mortality (OR 3.46, 95% CI 2.34 to 5.11, p <0.001), and bleeding
      complications (OR 2.36, 95% CI 1.70 to 3.25, p <0.001). In subgroup analyses,
      similar trends were observed in both men and women, and in both patients with
      acute coronary syndrome and stable coronary artery disease. In conclusion, a low
      baseline hemoglobin is a simple and powerful predictor of poor outcomes in
      patients who undergo PCI.

PMID- 29361290
TI  - Analysis of Regional Variation in Transcatheter Aortic Valve Implantation and
      Overall Aortic Valve Replacement.

PMID- 29361291
TI  - Takotsubo Syndrome and Cancer.

PMID- 29361292
TI  - Child road traffic injury mortality in Victoria, Australia (0-14 years), the need
      for targeted action.
AB  - INTRODUCTION: Extensive efforts to reduce unintentional injury were enacted in
      the last three decades of the 20th century. Examination of road traffic injury
      mortality indicates the extent of fatal, unintentional child injuries (0-14
      years) future interventions must address. AIMS: (1) describe in-depth child road
      traffic injury (RTI) deaths 2001-2012 in Victoria, Australia (2) identify the
      potential preventability of the RTI causes by currently available countermeasures
      and scope for enhanced implementation and novel solutions. METHOD: Fatal
      Victorian child injury data were extracted from the National Coronial Information
      System (NCIS) for the 12 year period January 2001-December 2012. All on-road data
      was analysed. Data for passenger and pedestrian deaths was examined in depth.
      Associated factors were determined using univariate and pairwise analysis of
      factors. Published WHO key prevention strategies, and the recent literature were
      reviewed, focusing on the identified fatalities among children 0-14 years.
      RESULTS: For 172 RTI deaths, head injury was the leading medical cause of death
      (68%). Significantly, the most vulnerable age group for both passengers and
      pedestrians was 0-4 years. Rural children were over-represented with children
      aged 0-4 years at greatest risk. Common factors for occupants were loss of
      control and veering to the incorrect side. For pedestrians the major factors
      related to rural residence and supervision. DISCUSSION AND CONCLUSIONS: This
      study confirms that RTIs are complex and follow chains of events. Numerous
      promising interventions were identified. Wider implementation of these advanced
      engineering, education and enforcement strategies may further improve mortality
      rates in Victoria. Feasible solutions for aspects of the child pedestrian problem
      remain elusive. This study describes the RTI problem in greater depth than
      previous studies and reveals that some existing measures are not fully
      implemented. The need for targeted action in: 0-4 year olds; head injury; and
      rural regions of Victoria is highlighted. The need for a safe systems approach is
      paramount.

PMID- 29361293
TI  - ICS classification system of infected osteosynthesis: Long-term results.
AB  - The best treatment strategy for infected osteosyntheses is still debated. While
      hardware removal or eventually early device exchange may be necessary in most of
      the cases, temporary hardware retention until fracture healing can be a valid
      alternative option in others. Aim of the present study is to report the long-term
      results of 215 patients with infected osteosyntheses, treated according to the
      ICS (Infection, Callus, Stability) classification in two Italian hospitals.
      Patients classified as ICS Type 1 (N = 83) feature callus progression and
      hardware stability, in spite of the presence of infection; these patients were
      treated with suppressive antibiotic therapy coupled with local debridement in
      18.1% of the cases, and no hardware removal until bone healing. Type 2 patients
      (N = 75) are characterized by the presence of infection and hardware stability,
      but no callus progression; these patients were treated as Type 1 patients, but
      with additional callus stimulation therapies. Type 3 patients (N = 57), showing
      infection, no callus progression and loss of hardware stability, underwent
      removal and exchange of the fixation device. Considering only the initial
      treatment, performed according to the ICS classification, at a minimum 5 years
      follow up, 89.3% achieved bone healing and 93.5% did not show infection
      recurrence. The ICS classification appears as a useful and reliable tool to help
      standardizing the decision-making process in treating infected osteosynthesis
      with the most conservative approach.

PMID- 29361294
TI  - CaP cement is equivalent to iliac bone graft in filling of large metaphyseal
      defects: 2 year prospective randomised study on distal radius osteotomies.
AB  - The purpose of this prospective randomised study was to compare the clinical and
      radiological outcomes of injectable CaP bone cement with corticocancellous bone
      graft used to fill voids after corrective opening wedge osteotomies in the distal
      radius. 17 women/3 men, median age 56 (51.3; 61.0), underwent an open-wedge
      osteotomy of a dorsal malunion in the distal radius randomised to filling the
      defect either with bone graft (10) or CaP bone cement (10). Dorsal titanium
      locking plates were used and the wrist was plastered for 8 weeks. Follow-ups for
      24 months included X-rays, CT scans, VAS on wrist and iliac crest, grip strength,
      ROM, Quick-DASH and Gartland & Werley scores. No difference was found between the
      2 groups as to clinical outcome or radiological results with no loss of
      reduction. One bone graft patient developed a pseudarthrosis and one CaP patient
      suffered a plate fracture 6 months post-operatively. CaP bone cement is a good
      alternative to bone graft as a void filler in open-wedge osteotomies of the
      distal radius. The procedure is shorter, easier with the post-operative advantage
      of no donor site pain. Level of Evidence Randomised controlled trial. Level I
      evidence.

PMID- 29361295
TI  - Treatment of acute achilles tendon rupture with the panda rope bridge technique.
AB  - INTRODUCTION: Although nonsurgical methods and many surgical techniques have been
      developed for repairing a ruptured Achilles tendon, there is no consensus on its
      best treatment. In this article, a novel minimally invasive technique called the
      Panda Rope Bridge Technique (PRBT) is described. METHODS: Patient with acute
      Achilles tendon rupture was operated on in the prone position. The PRBT begin
      with making the proximal bridge anchor (Krackow sutures in the myotendinous
      junction), the distal bridge anchor (two suture anchors in the calcaneus bone)
      and the ropes (threads of the suture anchors) stretched between the anchor sites.
      Then a small incision was made to debride and reattach the stumps of ruptured
      tendon. After the surgery, no cast or splint fixation was applied. All patients
      performed enhanced recovery after surgery (ERAS), which included immediate ankle
      mobilisation from day 1, full weight-bearing walking from day 5 to 7, and
      gradually take part in athletic exercises from 8 weeks postoperatively. RESULTS:
      PBRT was performed in 11patients with acute Achilles tendon rupture between June
      2012 and June 2015. No wound infection, fistula, skin necrosis, sural nerve
      damage, deep venous thrombosis or tendon re-rupture was found. One year after the
      surgery, all patients reported 100 AOFAS ankle-hindfoot score points and the mean
      ATRS was 96.6. CONCLUSION: The PRBT is a simple, effective and minimally invasive
      technique, with no need for immobilisation of the ankle, making possible
      immediate and aggressive postoperative rehabilitation.

PMID- 29361296
TI  - Peri-operative chest physiotherapy for paediatric cardiac patients: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Chest physiotherapy (CPT) is implemented before and after congenital
      heart disease (CHD) surgery in paediatrics to prevent and treat postoperative
      pulmonary complications (PPC). Currently, there are no systematic reviews or meta
      analyses on the efficacy of CPT in this population. OBJECTIVE: To conduct a
      systematic review and meta-analysis to determine whether peri-operative CPT is
      safe and effective for paediatric patients with CHD. DATA SOURCES: A literature
      search was conducted on PEDro, MEDLINE, CINAHL, Informit, The Cochrane Library
      and Scopus in March and April 2016. ELIGIBILITY CRITERIA: English peer-reviewed
      articles that utilised CPT before or after cardiac surgery for paediatric CHD.
      Systematic reviews were excluded. DATA EXTRACTION AND SYNTHESIS: Completed by two
      independent researchers using the Crowe Critical Appraisal Tool. Data were
      collated using a piloted data extraction tool. Mix Version 2.0.1.4 was used for
      meta-analysis, and data were extracted using an odds ratio (with a random effects
      model). RESULTS: Eleven studies met the inclusion criteria for the systematic
      review. Variable results were found regarding the effect of CPT on peripheral
      oxygen saturation and pain. Meta-analysis showed that CPT did not prevent
      pneumonia (odds ratio (OR) 2.01; 95% confidence interval (CI) 0.80 to 5.05;
      P=0.13), and did not prevent or treat atelectasis (OR 1.27; 95% CI 0.18 to 8.87;
      P=0.81). LIMITATIONS: There was a lack of high-quality studies. The included
      studies were comprised of heterogeneous treatment, limiting external validity.
      CONCLUSION: Active therapies such as mobilisation, deep breathing and incentive
      spirometry were more effective than passive treatment. Percussion led to oxygen
      desaturation, and percussion, vibration and suctioning increased the risk of
      developing atelectasis. Systematic review registration number CRD42015024768.

PMID- 29361297
TI  - Why participants in The United Kingdom Rotator Cuff Tear (UKUFF) trial did not
      remain in their allocated treatment arm: a qualitative study.
AB  - OBJECTIVE: The UKUFF trial was a three-way parallel group randomised trial
      comparing surgical and non-surgical treatments for people with rotator cuff tears
      of their shoulder. High crossover between arms in the UKUFF led to the original
      trial design being reconfigured; 'Rest then Exercise' was halted. This study
      explored why participants recruited did not remain within allocated treatment
      arms and explored crossover and surgical decision making. DESIGN: A qualitative
      phenomenological approach. PARTICIPANTS: Purposive sampling (n=18) included
      participants randomised to 'Rest then Exercise' arm considered least likely to
      proceed to surgery but who had surgery, plus participants from all arms not
      having surgery. METHODS: In-depth, semi-structured interviews were recorded and
      transcribed. Field-notes, memos, member-checking and a reflexive diary were used.
      DATA ANALYSES: In accordance with Interpretative Phenomenological Analysis. Peer
      review, code-recode audits and constant comparison occurred throughout. RESULTS:
      1. Impact of symptoms and diagnosis: these influenced crossover; long durations
      of severe pain and failed conservative treatment increased eagerness for surgery.
      2. Perceptions and expectations of treatment: surgery provided hope for
      participants, especially when "Rest then Exercise" was perceived as having
      previously failed. Surgeons were perceived to believe "tears need repairing". 3.
      Professionals know best: autonomy and communication: patients deciding not to
      have surgery had to actively leave the surgical waiting list. Increasing age,
      carer role, self-employment, co-morbidity and improving symptoms were reasons
      described for declining surgery. CONCLUSIONS: Most participants had failed
      conservative treatment before trial entry and described strong preferences
      regarding treatment. Trials should demonstrate patient and clinician equipoise
      but participants' rarely described equipoise. If conservative treatments are
      usually provided sequentially in clinical practice, it may be inappropriate to
      include them as comparators in surgical trials. This is a qualitative study and
      not eligible for trial registration since it was carried out independently of the
      UKUFF trial (UKUFF ISRCTN97804283 Date assigned 29/06/2007).

PMID- 29361298
TI  - What is the patient acceptability of real time 1:1 videoconferencing in an
      orthopaedics setting? A systematic review.
AB  - BACKGROUND: Real time 1:1 videoconferencing (VC) has the potential to play an
      important role in the management of orthopaedic pathologies. Despite positive
      reporting of telemedicine studies uptake in clinical practice remains low.
      Acceptability to patients is an important element of system take-up in
      telemedicine and a focus towards qualitative methodology may explore the
      underlying reasons behind its acceptability. In this paper we have systematically
      reviewed qualitative studies that include evidence about patient responses to VC
      services in an orthopaedic setting. OBJECTIVES: To determine whether real time
      1:1 videoconferencing is acceptable to patients in an orthopaedic setting. DATA
      SOURCES: MEDLINE, AMED, PsychINFO, CINAHL, SCOPUS, Cochrane Database, Evidence
      Search and Open Grey were searched with forwards and backwards reference
      screening of eligible papers. ELIGIBILITY CRITERIA: Qualitative studies exploring
      the acceptability of VC in an orthopaedic setting were included. STUDY APPRAISAL
      AND SYNTHESIS METHODS: Studies were appraised using the CASP tool. A Directed
      Content Framework Analysis was conducted using Normalisation Process Theory.
      RESULTS: Four studies were included for review. The themes for the four studies
      did not overlap and did not report clinician acceptability of VC. The Directed
      Content Analysis of these papers using Normalisation Process Theory highlighted
      factors which contribute towards its acceptability. CONCLUSIONS: All studies
      concluded that the use of VC was acceptable. Further qualitative research
      exploring both patient and clinician acceptability is required utilising a
      theoretical framework to allow for repeatability and generalisability. Systematic
      Review Registration Number: PROSPERO CRD42015024944.

PMID- 29361299
TI  - Extracorporeal membrane oxygenation as a direct bridge to heart transplantation
      in adults.
AB  - OBJECTIVES: Venoarterial extracorporeal membrane oxygenation (ECMO) use as a
      bridge to transplant is extremely infrequent in adults. We investigated patient
      outcomes of the use of ECMO as bridge to transplant. METHODS: United Network of
      Organ Sharing provided de-identified patient-level data. Between 2003 and 2016,
      25,168 adult recipients were identified. Of these, 107 (0.4%) were bridged with
      ECMO and 6148 (24.4%) were bridged with a continuous-flow left ventricular assist
      device. RESULTS: Patients in ECMO group were younger, more likely to have
      severely disabled functional status, shorter waitlist time, and were more
      frequently mechanically ventilated than were patients in the continuous-flow left
      ventricular assist device group. Kaplan-Meier analysis demonstrated estimated
      posttransplant survival of 73.1% versus 93.1% at 90 days (P < .001) and 67.4%
      versus 82.4% at 3 years (P < .001) in ECMO and continuous-flow left ventricular
      assist device groups, respectively. Analysis of a propensity-matched cohort still
      demonstrated a lower survival in ECMO group at 90 days (74.8% vs 88.8%; P = .025)
      and 3 years (69.3% vs 82.2%; P = .054). Among the ECMO patients, multivariable
      logistic and Cox regression analyses showed model for end-stage liver disease
      excluding international normalized ratio (MELD-XI) score to be the sole
      contributor to both 90-day (odds ratio, 1.94; 95% confidence interval, 1.00-3.76;
      P = .050) and 3-year mortality (hazard ratio, 1.47; 95% confidence interval, 1.16
      1.88; P = .002). ECMO-supported patients with a high MELD-XI score (>17) were
      associated with poor posttransplant survival compared with those with a low MELD
      XI score (<13) (90 day, 54.4% vs 85.0% [P < .001] and 3 year, 49.5% vs 73.5% [P <
      .001]). CONCLUSIONS: Bridge to transplant with ECMO was associated with increased
      early/mid-term mortality, especially in patients with a high MELD-XI score who
      demonstrated > 50% 3-year mortality. These findings may help to inform future
      organ allocation policies.

PMID- 29361301
TI  - Discussion.

PMID- 29361300
TI  - Cardiothoracic surgery training grants provide protected research time vital to
      the development of academic surgeons.
AB  - BACKGROUND: The Ruth L. Kirschstein Institutional National Research Service Award
      (T32) provides institutions with financial support to prepare trainees for
      careers in academic medicine. In 1990, the Cardiac Surgery Branch of the National
      Heart, Lung and Blood Institute (NHLBI) was replaced by T32 training grants,
      which became crucial sources of funding for cardiothoracic (CT) surgical
      research. We hypothesized that T32 grants would be valuable for CT surgery
      training and yield significant publications and subsequent funding. METHODS: Data
      on all trainees (past and present) supported by CT T32 grants at two institutions
      were obtained (T32), along with information on trainees from two similarly sized
      programs without CT T32 funding (Non-T32). Data collected were publicly available
      and included publications, funding, degrees, fellowships, and academic rank. Non
      surgery residents and residents who did not pursue CT surgery were excluded.
      RESULTS: Out of 76 T32 trainees and 294 Non-T32 trainees, data on 62 current
      trainees or current CT surgeons (T32: 42 vs Control: 20) were included. Trainees
      who were supported by a CT T32 grant were more likely to pursue CT surgery after
      residency (T32: 40% [30/76] vs Non-T32: 7% [20/294], P < .0001), publish
      manuscripts during residency years (P < .0001), obtain subsequent NIH funding
      (T32: 33% [7/21] vs Non-T32: 5% [1/20], P = .02), and pursue advanced fellowships
      (T32: 41% [9/22] vs Non-T32: 10% [2/20], P = .02). CONCLUSIONS: T32 training
      grants supporting CT surgery research are vital to develop academic surgeons.
      These results support continued funding by the NHLBI to effectively develop and
      train the next generation of academic CT surgeons.

PMID- 29361302
TI  - Irreversible cardiac failure with intraventricular thrombosis: A novel technique
      of paracorporeal biventricular assist device implantation with ventricles
      excision.

PMID- 29361303
TI  - Virtual surgical planning, flow simulation, and 3-dimensional electrospinning of
      patient-specific grafts to optimize Fontan hemodynamics.
AB  - BACKGROUND: Despite advances in the Fontan procedure, there is an unmet clinical
      need for patient-specific graft designs that are optimized for variations in
      patient anatomy. The objective of this study is to design and produce patient
      specific Fontan geometries, with the goal of improving hepatic flow distribution
      (HFD) and reducing power loss (Ploss), and manufacturing these designs by
      electrospinning. METHODS: Cardiac magnetic resonance imaging data from patients
      who previously underwent a Fontan procedure (n = 2) was used to create 3
      dimensional models of their native Fontan geometry using standard image
      segmentation and geometry reconstruction software. For each patient, alternative
      designs were explored in silico, including tube-shaped and bifurcated conduits,
      and their performance in terms of Ploss and HFD probed by computational fluid
      dynamic (CFD) simulations. The best-performing options were then fabricated using
      electrospinning. RESULTS: CFD simulations showed that the bifurcated conduit
      improved HFD between the left and right pulmonary arteries, whereas both types of
      conduits reduced Ploss. In vitro testing with a flow-loop chamber supported the
      CFD results. The proposed designs were then successfully electrospun into tissue
      engineered vascular grafts. CONCLUSIONS: Our unique virtual cardiac surgery
      approach has the potential to improve the quality of surgery by manufacturing
      patient-specific designs before surgery, that are also optimized with balanced
      HFD and minimal Ploss, based on refinement of commercially available options for
      image segmentation, computer-aided design, and flow simulations.

PMID- 29361304
TI  - Impact of proximal radiopaque coronary bypass graft markers on postbypass surgery
      coronary angiography.
AB  - BACKGROUND: Implantation of radiopaque bypass graft markers during coronary
      artery bypass surgery (CABG) has the potential of facilitating subsequent
      coronary angiography. This study sought to investigate the impact of proximal
      coronary bypass graft markers on angiographic outcomes during subsequent coronary
      angiography in a large cohort. METHODS AND RESULTS: Between 2005 and 2016, we
      enrolled 1378 patients (331 with and 1047 without bypass graft markers) with a
      history of CABG who underwent their first subsequent coronary angiography at our
      institution. Primary endpoints were radiation time and absolute amount of
      contrast media used. In unadjusted analyses, radiation time, duration of
      angiography, dose area product, and the amount of contrast agent were
      significantly lower in patients with proximal bypass graft markers (P < .001).
      After full adjustment, proximal coronary bypass graft markers remained a
      significant predictor for less radiation time and a lower consumption of contrast
      agent but not for dose area product, which was mainly associated with body mass
      index and sex. Bypass graft markers were not associated with a lower graft
      patency. CONCLUSIONS: Radiopaque coronary bypass graft markers can improve the
      detection of bypass grafts during subsequent coronary angiography and are
      associated with a lower radiation time and less consumption of contrast agent.
      Thus, this easy and cost-efficient technique might significantly reduce the risk
      of coronary angiography after CABG.

PMID- 29361305
TI  - Identification of Drug Characteristics for Implementing Multiregional Clinical
      Trials Including Japan.
AB  - PURPOSE: Multiregional clinical trials (MRCT) are a standard strategy used to
      improve global drug approval efficiency and the feasibility of clinical trials.
      Japan is the world's third largest drug market with a unique health care system,
      making it a key inclusion as an operational region for MRCT (MRCT-JP) for global
      drug development. We aimed to identify the factors required for efficient drug
      development by comprehensively reviewing the clinical trials of drugs approved in
      Japan to identify the factors associated with whether or not MRCT-JP is
      implemented. METHODS: We surveyed the review reports and summaries of application
      data published by the Pharmaceuticals and Medical Devices Agency. We identified
      drugs for which the clinical trial data package included MRCT-JP and selected the
      same number of drugs for which the clinical trial data package did not include
      MRCT-JP from the most recent survey period for comparison. We also examined other
      publication information, in addition to the review reports, as necessary. The
      influence of each explanatory variable was analyzed by logistic regression
      analysis, with whether or not MRCT-JP was implemented as the explanatory
      variable. Statistical significance was set at 5%. FINDINGS: In the survey period
      up to September 2017, 165 drugs developed with MRCT-JP were approved for
      manufacture and sale in Japan. "Respiratory system," "inhalation," "biological
      drug," and "under review" evaluation status for the United States, European
      Union, and other areas, "approved" evaluation status for the United States, "new
      ingredients," "priority review," "non-Japanese firm," and "Top 1-10" and "Top 11
      20" drug sales rankings for pharmaceutical companies were identified as potential
      factors leading to the implementation of MRCT-JP. In contrast, "general anti
      infectives for systemic use," "various," "external," "chemical compound,"
      "unsubmitted" evaluation status for both the United States and European Union,
      and "Top 51+" drug sales rankings were potential factors for not implementing
      MRCT-JP. IMPLICATIONS: Therapeutic classification and agent type, in addition to
      capital type and United States and European Union evaluation status suggested by
      a previous study, were associated with implementing MRCT-JP. It is important to
      determine the best way to utilize MRCT-JP to maximize the value of products. Our
      findings were based on successful cases and may therefore be helpful for
      designing clinical development plans. Appropriate use of MRCT-JP will improve
      productivity in the pharmaceutical industry.

PMID- 29361306
TI  - Immunoribosomes: Where's there's fire, there's fire.
AB  - The MHC class I antigen presentation pathway enables T cell immunosurveillance of
      cancer cells, viruses and other intracellular pathogens. Rapidly degraded newly
      synthesized proteins (DRiPs) are a major source of self-, and particularly, viral
      antigenic peptides. A number of findings support the idea that a substantial
      fraction of antigenic peptides are synthesized by "immunoribosomes", a subset of
      translating ribosomes that generate class I peptides with enhanced efficiency.
      Here, we review the evidence for the immunoribosome hypothesis.

PMID- 29361307
TI  - Renal tubule injury: a driving force toward chronic kidney disease.
AB  - Renal tubules are the major component of the kidney and are vulnerable to a
      variety of injuries including hypoxia, proteinuria, toxins, metabolic disorders,
      and senescence. It has long been believed that tubules are the victim of injury.
      In this review, we shift this concept to renal tubules as a driving force in the
      progression of kidney diseases. In response to injury, tubular epithelial cells
      undergo changes and function as inflammatory and fibrogenic cells, with the
      consequent production of various bioactive molecules that drive interstitial
      inflammation and fibrosis. Innate immune-sensing receptors on the tubular
      epithelium also aggravate immune responses. Necroinflammation, an
      autoamplification loop between tubular cell death and interstitial inflammation,
      leads to the exacerbation of renal injury. Furthermore, tubular cells also play
      an active role in progressive renal injury via emerging mechanisms associated
      with a partial epithelial-mesenchymal transition, cell-cycle arrest at both G1/S
      and G2/M check points, and metabolic disorder. Thus, a better understanding the
      mechanisms by which tubular injury drives inflammation and fibrosis is necessary
      for the development of therapeutics to halt the progression of chronic kidney
      disease.

PMID- 29361308
TI  - Maternal depressive symptoms and infant healthcare utilization: The moderating
      role of prenatal mindfulness.

PMID- 29361309
TI  - In-vitro wear of natural tooth surface opposed with zirconia reinforced lithium
      silicate glass ceramic after accelerated ageing.
AB  - OBJECTIVE: To evaluate the effect of different pH media on zirconia-reinforced
      lithium silicate glass ceramic and how they interact with opposing dentition
      after being aged in different pH cycling and high temperature conditions.
      METHODS: Twenty-five rectangular shaped specimens were prepared from lithium
      silicate reinforced with zirconia blanks (Suprinity, Vita Zahnfabrick) and stored
      in different pH media (3 & 7.2) for different periods (24h & 7 days) at
      temperature (55 degrees C). After their surface roughness (Ra) evaluation, aged
      ceramic specimens were subjected to cyclic abrasive wear with opposing natural
      teeth enamel for 150,000 cycles using a chewing simulator. Weight loss and
      Scanning Electron Microscope (SEM) images were used to evaluate the cyclic wear
      results. RESULTS: After different pH storage, ceramic group stored at 3 pH for 1
      W (1 week) gave significantly higher mean Ra value (0.618MUm+/-0.117) than
      control lowest mean value (0.357MUm+/-0.054) before cyclic wear. On the other
      hand, it caused the least significant weight loss value (0.004gm+/-0.001) to
      opposing tooth enamel. There was significant tooth enamel weight loss (0.043gm+/
      0.004) when opposed with ceramic group stored in 3 pH media for 24h (24-H). Their
      SEM images showed a prominent wear scar on enamel cusp tip. There was a
      significant increase in surface roughness Ra of ceramic material after abrasive
      cyclic wear. SIGNIFICANCE: Great attention should be paid to Ra of this type of
      glass ceramic even if it is considered as minimal values. It can induce a
      significant amount of enamel tooth wear after a period equivalent to one year of
      intra-oral function rather than the significantly higher surface Ra of such
      ceramic type can do.

PMID- 29361310
TI  - Kounys syndrome after rocuronium administration.
AB  - Kounis syndrome encompasses concepts including angina and allergic infarction
      described in relation to exposure to different allergens. The aim of this article
      is to describe a case of Kounis Syndrome type II after exposure to rocuronium as
      well as the patholophysiology and the treatment of this syndrome.

PMID- 29361311
TI  - Perioperative hyperoxia: Myths and realities.

PMID- 29361312
TI  - The usefulness of interpectoral block as an analgesic technique in breast cancer
      surgery.
AB  - OBJECTIVE: To compare the analgesic efficacy of continuous interpectoral block
      (CIPB) compared to intravenous analgesia (IV) after breast surgery. MATERIAL AND
      METHOD: A prospective, comparative and randomised study of women aged from 18
      75years, ASAI-III, operated for breast cancer. In group1 (CIPB) after general
      anaesthetic, an ultrasound-guided interpectoral catheter was placed and 30mL of
      0.5% ropivacaine was administered through it. In the event of an increase in
      heart rate and blood pressure >15% after the surgical incision, intravenous
      fentanyl 1MUg.kg-1 was administered, repeating the dose as necessary. In the
      postoperative period, perfusion of ropivacaine 0.2% 5mL.h-1; with PCA bolus
      5mL/30minutes was administered through the catheter for 24hours and rescue
      analgesia prescribed with 5mg subcutaneous morphine chloride. In group2 (IV),
      after induction of general anaesthesia, intravenous fentanyl was administered in
      the same way as in the other group. The patients received metamizole 2g with
      dexketoprofen 50mg and ondansetron 4mg postoperatively followed by perfusion of
      metamizole 4%, tramadol 0.2% and ondansetron 0.08% 2ml.h-1; with PCA bolus
      2mL/20min for 24hours. The same rescue analgesia was prescribed. The principal
      variables recorded were pain at rest and during movement, according to a simple
      verbal scale (VAS 0-10) and the rescue analgesia required on discharge from
      recovery, at 12 and at 24hours. RESULTS: 137 patients were included: 81 in group1
      (59.12%) and 56 in group2 (40.87%). No significant differences were observed in
      the analgesia between either group, but differences were observed in the dose of
      intraoperative fentanyl (P<.05). Differences that were not significant were
      observed in the rescue analgesia required on recovery (10% fewer on group1).
      CONCLUSIONS: Both techniques provided effective postoperative analgesia, but the
      CIPB group required significantly less intraoperative fentanyl.

PMID- 29361313
TI  - Big Strides in Cellular MicroRNA Expression.
AB  - A lack of knowledge of the cellular origin of miRNAs has greatly confounded
      functional and biomarkers studies. Recently, three studies characterized miRNA
      expression patterns across >78 human cell types. These combined data expand our
      knowledge of miRNA expression localization and confirm that many miRNAs show cell
      type-specific expression patterns.

PMID- 29361314
TI  - Simvastatin alters M1/M2 polarization of murine BV2 microglia via Notch
      signaling.
AB  - Microglia play a critical role in the regulation of CNS immune function, which
      can be greatly affected by M1/M2 polarization. The role of Notch signaling in
      Statins induced alteration of M1/M2 polarization in BV2 cells was assessed in
      this study. M1 markers in LPS and Jagged-1 treated group were significantly
      increased and such increase was attenuated by simvastatin; however, M2 markers
      were enhanced. Moreover, simvastatin enhance the expression of Notch signaling
      molecules, and its regulatory effects were blocked in Notch1 knocked down cells.
      In conclusion, these findings indicated that simvastatin alters M1/M2
      polarization of murine BV2 microglia via Notch signaling.

PMID- 29361315
TI  - Corrigendum to "Structure, folding and stability of a minimal homologue from
      Anemonia sulcata of the sea anemone potassium channel blocker ShK" [Peptides 99
      (2018) 169-178].

PMID- 29361316
TI  - Structure and Conformational Dynamics of the Human Spliceosomal Bact Complex.
AB  - The spliceosome is a highly dynamic macromolecular complex that precisely excises
      introns from pre-mRNA. Here we report the cryo-EM 3D structure of the human Bact
      spliceosome at 3.4 A resolution. In the Bact state, the spliceosome is activated
      but not catalytically primed, so that it is functionally blocked prior to the
      first catalytic step of splicing. The spliceosomal core is similar to the yeast
      Bact spliceosome; important differences include the presence of the RNA helicase
      aquarius and peptidyl prolyl isomerases. To examine the overall dynamic behavior
      of the purified spliceosome, we developed a principal component analysis-based
      approach. Calculating the energy landscape revealed eight major conformational
      states, which we refined to higher resolution. Conformational differences of the
      highly flexible structural components between these eight states reveal how
      spliceosomal components contribute to the assembly of the spliceosome, allowing
      it to generate a dynamic interaction network required for its subsequent
      catalytic activation.

PMID- 29361317
TI  - Associations between ambient air pollution and daily mortality in a cohort of
      congestive heart failure: Case-crossover and nested case-control analyses using a
      distributed lag nonlinear model.
AB  - BACKGROUND: Persons with congestive heart failure may be at higher risk of the
      acute effects related to daily fluctuations in ambient air pollution. To meet
      some of the limitations of previous studies using grouped-analysis, we developed
      a cohort study of persons with congestive heart failure to estimate whether daily
      non-accidental mortality were associated with spatially-resolved, daily exposures
      to ambient nitrogen dioxide (NO2) and ozone (O3), and whether these associations
      were modified according to a series of indicators potentially reflecting
      complications or worsening of health. METHODS: We constructed the cohort from the
      linkage of administrative health databases. Daily exposure was assigned from
      different methods we developed previously to predict spatially-resolved, time
      dependent concentrations of ambient NO2 (all year) and O3 (warm season) at
      participants' residences. We performed two distinct types of analyses: a case
      crossover that contrasts the same person at different times, and a nested case
      control that contrasts different persons at similar times. We modelled the
      effects of air pollution and weather (case-crossover only) on mortality using
      distributed lag nonlinear models over lags 0 to 3 days. We developed from
      administrative health data a series of indicators that may reflect the underlying
      construct of "declining health", and used interactions between these indicators
      and the cross-basis function for air pollutant to assess potential effect
      modification. RESULTS: The magnitude of the cumulative as well as the lag
      specific estimates of association differed in many instances according to the
      metric of exposure. Using the back-extrapolation method, which is our preferred
      exposure model, we found for the case-crossover design a cumulative mean
      percentage changes (MPC) in daily mortality per interquartile increment in NO2
      (8.8 ppb) of 3.0% (95% CI: -0.9, 6.9%) and for O3 (16.5 ppb) 3.5% (95% CI: -4.5,
      12.1). For O3 there was strong confounding by weather (unadjusted MPC = 7.1%; 95%
      CI: 1.7, 12.7%). For the nested case-control approach the cumulative MPC for NO2
      in daily mortality was 2.9% (95% CI: -0.9, 6.9%) and for O3 7.3% (95% CI: 3.0,
      11.9%). We found evidence of effect modification between daily mortality and
      cumulative NO2 and O3 according to the prescribed dose of furosemide in the
      nested case-control analysis, but not in the case-crossover analysis.
      CONCLUSIONS: Mortality in congestive heart failure was associated with exposure
      to daily ambient NO2 and O3 predicted from a back-extrapolation method using a
      land use regression model from dense sampling surveys. The methods used to assess
      exposure can have considerable influence on the estimated acute health effects of
      the two air pollutants.

PMID- 29361318
TI  - Zika virus encephalitis.

PMID- 29361319
TI  - A 60-Year-Old Male Smoker With Chronic Obstructive Pulmonary Disease and
      Hypereosinophilia.

PMID- 29361320
TI  - Medical Care According to Risk Level and Adaptation to Spanish COPD Guidelines
      (Gesepoc): The Epoconsul Study.
AB  - INTRODUCTION: EPOCONSUL is the first national audit to analyze medical care for
      COPD in pulmonology departments in Spain. The main objective was to perform a
      retrospective analysis to determine the distribution of GesEPOC 2017 COPD risk
      levels and to evaluate clinical activity according to the new recommendations.
      MATERIAL AND METHODS: This is a cross-sectional clinical audit in which
      consecutive COPD cases were recruited over one year. The study evaluated risk and
      clinical phenotype according to GesEPOC 2017, and their correlation with the
      clinical interventions employed. RESULTS: The most common risk category was high
      risk (79.8% versus 20.2%; p < 0.001), characterized by a higher level of severity
      on BODE and BODEx indexes, and a higher comorbidity burden. The most common
      phenotype was non-exacerbator. The most commonly used treatment in low-risk
      patients was bronchodilator monotherapy (34.8%) and triple therapy in high-risk
      patients (53.7%). High risk was most frequently characterized by phenotype (57.6%
      versus 52%; p = 0.014) and pulmonary function test results: lung volume (47.7%
      versus 35.8%; p < 0.001), lung diffusion (51.4% versus 42.1%; p < 0.001) and walk
      test (37.8% versus 15.8%; p < 0.001). CONCLUSIONS: Most patients treated in
      pulmonology departments were high-risk and non-exacerbator phenotype. Clinical
      interventions differed according to risk level and mainly followed GesEPOC
      recommendations, although there is significant room for improvement.

PMID- 29361321
TI  - Centennial record of anthropogenic impacts in Galveston Bay: Evidence from trace
      metals (Hg, Pb, Ni, Zn) and lignin oxidation products.
AB  - During the 20th century the impacts of industrialization and urbanization in
      Galveston Bay resulted in significant shifts in trace metals (Hg, Pb, Ni, Zn) and
      vascular plant biomarkers (lignin phenols) recorded within the surface sediments
      and sediment cores profile. A total of 22 sediment cores were collected in
      Galveston Bay in order to reconstruct the historical input of Hg, Pb, Ni, Zn and
      terrestrial organic matter. Total Hg (T-Hg) concentration ranged between 6 and
      162 ng g-1 in surface sediments, and showed decreasing concentrations southward
      from the Houston Ship Channel (HSC) toward the open estuary. Core profiles of T
      Hg and trace metals (Ni, Zn) showed substantial inputs starting in 1905, with
      peak concentrations between 1960 and 1970's, and decreasing thereafter with
      exception to Pb, which peaked around 1930-1940s. Stable carbon isotopes and
      lignin phenols showed an increasing input of terrestrial organic matter driven by
      urban development within the watershed in the early 1940s. Both the enrichment
      factor and the geoaccumulation index (Igeo) for T-Hg as a measure of the
      effectiveness of environmental management practices showed substantial
      improvements since the 1970s. The natural recovery rate in Galveston Bay since
      the peak input of T-Hg was non-linear and displayed a slow recovery during the
      twenty-first century.

PMID- 29361322
TI  - Pulmonary aspergilloma mimicking synchronous lung cancer on PET/CT in a patient
      with head and neck cancer.

PMID- 29361323
TI  - Accuracy of the TIMI and GRACE scores in predicting coronary disease in patients
      with non-ST-elevation acute coronary syndrome.
AB  - INTRODUCTION: The GRACE and TIMI scores have been well validated for assessment
      of prognosis in non-ST-elevation acute coronary syndrome (NSTE-ACS). However,
      their value in predicting coronary artery disease (CAD) has been little studied.
      We aimed to assess the relationship between these scores and the extent of
      coronary disease. METHODS: We analyzed 238 consecutive patients admitted for NSTE
      ACS and undergoing a coronary angiogram during hospitalization. The severity of
      CAD was assessed using the SYNTAX score. Obstructive CAD was defined as >=50%
      stenosis in the left main or >=70% stenosis in other vessels. Severe CAD was
      defined as a SYNTAX score >32. The Pearson test was used to assess the
      correlation between scores. RESULTS: The SYNTAX score was higher in patients at
      high risk (GRACE score: p<0.001 and TIMI score: p=0.001). Moreover, there was a
      significant positive correlation between the GRACE and SYNTAX scores (r=0.23,
      p<0.001) as well as between TIMI and SYNTAX (r=0.2, p=0.002). Both clinical
      scores can predict obstructive CAD moderately well (area under the curve [AUC]
      for GRACE score: 0.599, p=0.015; TIMI score: AUC 0.639, p=0.001) but not severe
      disease. A GRACE score of 120 and a TIMI score of 2 were predictive of
      obstructive CAD with, respectively, a sensitivity of 57% and 75.7% and a
      specificity of 61.8% and 47.9%. CONCLUSION: The GRACE and TIMI scores correlate
      moderately with the extent of coronary disease assessed by the SYNTAX score. They
      can predict obstructive CAD but not severe disease.

PMID- 29361324
TI  - Association between Medicare high-risk criteria and outcomes after carotid
      revascularization procedures.
AB  - BACKGROUND: The U.S. Centers for Medicare and Medicaid Services (CMS) has defined
      a set of high-risk criteria to help define patients who are appropriate for
      carotid artery stenting (CAS), but these criteria have never been validated. We
      aimed to validate the CMS high-risk criteria in a nationally representative
      cohort of patients undergoing CAS and carotid endarterectomy (CEA). METHODS: All
      patients undergoing CAS (with embolic protection) or CEA in the Vascular Quality
      Initiative (VQI) database (2013-2016) were included. Patients were stratified as
      being at normal risk (Nr) or high risk (Hr) for undergoing CEA on the basis of
      CMS criteria. Thirty-day and 2-year stroke outcomes were compared for CAS vs CEA
      in both the Nr and Hr groups using 1:1 coarsened exact matching and multivariable
      Cox proportional hazards modeling. RESULTS: A total of 51,942 patients (CAS,
      7030; CEA, 44,912) underwent carotid revascularization during the study period.
      Thirty-day (Nr, 1.7% vs 1.0%; Hr, 2.5% vs 1.4%) and 2-year (Nr, 1.9% vs 1.0%; Hr,
      2.4% vs 1.3%) stroke occurred more frequently after CAS vs CEA on crude analysis
      (P < .001). After matching 2920 pairs of patients on 18 preoperative variables,
      the risk of 30-day and 2-year stroke remained higher after CAS in the Hr group
      (30-day risk: hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.26-2.85; 2
      year risk: HR, 1.65; 95% CI, 1.05-2.60) but was similar for CAS vs CEA in the Nr
      group (30-day risk: HR, 0.97; 95% CI, 0.48-1.95; 2-year risk: HR, 1.49; 95% CI,
      0.76-2.90). CONCLUSIONS: These data suggest that the utility of CAS in Nr
      patients may be underappreciated, whereas the potential benefit of CAS in Hr
      patients may be overestimated. Re-evaluation of the criteria for identifying
      patients at high risk for CEA and the national guidelines on the indications for
      CAS is strongly indicated.

PMID- 29361325
TI  - The Dorsal Aponeurosis of the Thumb.
AB  - PURPOSE: To evaluate the thumb dorsal aponeurosis anatomy. Consideration of
      structural differences between the fingers and thumb will provide an improved
      clinical understanding of the thumb dorsal aponeurosis anatomy. METHODS: Ten
      fresh cadaver hands from 5 patients with an average age of 31.6 (range, 22-41)
      years were dissected. The thenar muscles were identified and insertion sites were
      documented. The fibers of the dorsal aponeurosis and contributions were
      identified. RESULTS: The flexor pollicis brevis superficial head contributed to
      the radial fibers of the dorsal aponeurosis in 8 specimens and contributed to the
      deep head in 1 specimen. The abductor pollicis brevis provided fibers to the
      radial dorsal aponeurosis in all 10 specimens. The oblique and transverse heads
      of the adductor pollicis contributed to the ulnar dorsal aponeurosis in 8 and 9
      hands, respectively. The fibers of the intrinsic apparatus were composed of 3
      major types: transverse, oblique, and long. CONCLUSIONS: This investigation
      provides a detailed anatomic study of the dorsal aponeurosis of the thumb with
      observation of both intrinsic and extrinsic contributions. CLINICAL RELEVANCE:
      Understanding the anatomy of the dorsal aponeurosis of the thumb remains
      important not only for evaluation of the classic Stener lesion, but also for the
      appropriate treatment of deformity, contracture, and neuromuscular disorders
      involving the thumb.

PMID- 29361326
TI  - Evidence-Based Review of Pharmacotherapy for Acute Agitation. Part 1: Onset of
      Efficacy.
AB  - BACKGROUND: The main goal of antipsychotic medication in the management of acute
      agitation in the emergency department is to rapidly induce calm without
      oversedation, enabling patients to participate in their own care. However, there
      is a paucity of comparative studies, particularly with newer fast-acting second
      generation antipsychotic agents. OBJECTIVE OF THE REVIEW: This structured
      evidence-based review compared the onset of efficacy of antipsychotic treatments
      for acute agitation using data from randomized controlled trials identified by a
      literature search of the PubMed database. RESULTS: Based on findings from 28
      blinded randomized controlled trials, onset of efficacy was rapid and generally
      observed at the first time point after intramuscular administration of
      ziprasidone (15-30 min) or olanzapine (15-30 min), but was more likely to be
      delayed with intramuscular haloperidol, even when combined with lorazepam (30-60
      min), and intramuscular aripiprazole (45-90 min). When administered orally, rapid
      onset of efficacy was also consistently observed at the first assessment time
      point with olanzapine (15-120 min), risperidone (30-120 min), and sublingual
      asenapine (15 min). Significant effects were apparent for inhaled loxapine within
      10-20 min. Effects were apparent within approximately 5-10 min with i.v.
      droperidol. Onset of efficacy was typically more rapid with second-generation
      antipsychotic agents than benzodiazepines, but data are limited. CONCLUSIONS:
      Although the patient populations of trials included in this review do not truly
      reflect that of the emergency department, the results provide useful information
      to emergency physicians on the rapid efficacy of certain newer-generation
      antipsychotic agents for the treatment of acutely agitated patients.

PMID- 29361327
TI  - Comparison of macular parameters after femtosecond laser-assisted and
      conventional cataract surgery in age-related macular degeneration.
AB  - PURPOSE: To evaluate differences in postoperative central macular thickness,
      central macular volume, corrected distance visual acuity (CDVA), and number of
      intravitreal anti-vascular endothelial growth factor (VEGF) injections between
      conventional and femtosecond laser-assisted cataract surgery in wet age-related
      macular degeneration (AMD). SETTING: Tertiary referral center, Lucerne,
      Switzerland. DESIGN: Retrospective case series. METHODS: Consecutive patients
      with AMD and cataract were enrolled between January 2010 and December 2015.
      Associations between postoperative changes in central macular thickness, central
      macular volume, CDVA, and number of anti-VEGF injections with type of surgery
      were assessed statistically. RESULTS: The study comprised 140 eyes (110
      patients). No differences in postoperative central macular thickness (-9.20 MUm;
      95% confidence interval [CI], -41.68 to 23.28; P = .576), central macular volume
      (-0.08 mm2; 95% CI, -0.36 to 0.19; P = .553), visual acuity (0.03 logarithm of
      the minimum angle of resolution; 95% CI, -0.09 to 0.15; P = .647) or
      postoperative number of anti-VEGF injections (0.30; 95% CI, -0.45 to 1.05; P =
      .427) were found between the femtosecond laser group and the conventional group
      over a mean follow-up of 619 days +/- 473 (SD). In the 33 eyes that had optical
      coherence tomography measurement within a postoperative period of 2 weeks, the
      central macular volume was significantly lower in femtosecond laser-treated eyes
      (-0.71 mm2; 95% CI, -1.19 to -0.23; P = .005). CONCLUSIONS: Overall, the
      postoperative course between wet AMD after femtosecond laser and conventional
      cataract surgery was equal. During the early follow-up, femtosecond laser-treated
      eyes had less subclinical macular edema, indicating a possible benefit for
      patients with macular vulnerability.

PMID- 29361328
TI  - Write a scientific paper (WASP) - a career-critical skill.
AB  - The ability to write a scientific paper (WASP) is becoming progressively more
      critical because the "publish or perish" mantra is increasingly valid in today's
      world where success is judged by number of publications and quality of
      publications based on journals which publish the researcher's work. These metrics
      are used to gauge applicants in often cut-throat competitions for jobs and/or
      career advancement. However, the science and art of paper-writing comprise a vast
      panoply of different skills, from writing a proposal, to ethics and data
      protection applications, to data collection and analysis, to writing and dealing
      with editors and authors, and so on. Over the next few issues, Early Human
      Development will embark on a series of Best Practice Guidelines that will outline
      and explain the various requisite WASP skills while providing practical
      guidelines for paper writing. The purpose is to impart the authors' collective
      experience to trainees in this crucial aspect of career progress. This first set
      of WASP papers will mainly focus on statistical analysis using ExcelTM.

PMID- 29361329
TI  - WASP (Write a Scientific Paper) using Excel - 1: Data entry and validation.
AB  - Data collection for the purposes of analysis, after the planning and execution of
      a research study, commences with data input and validation. The process of data
      entry and analysis may appear daunting to the uninitiated, but as pointed out in
      the 1970s in a series of papers by British Medical Journal Deputy Editor TDV
      Swinscow, modern hardware and software (he was then referring to the availability
      of hand calculators) permits the performance of statistical testing outside a
      computer laboratory. In this day and age, modern software, such as the ubiquitous
      and almost universally familiar Microsoft ExcelTM greatly facilitates this
      process. This first paper comprises the first of a collection of papers which
      will emulate Swinscow's series, in his own words, "addressed to readers who want
      to start at the beginning, not to those who are already skilled statisticians."
      These papers will have less focus on the actual arithmetic, and more emphasis on
      how to actually implement simple statistics, step by step, using Excel, thereby
      constituting the equivalent of Swinscow's papers in the personal computer age.
      Data entry can be facilitated by several underutilised features in Excel. This
      paper will explain Excel's little-known form function, data validation
      implementation at input stage, simple coding tips and data cleaning tools.

PMID- 29361330
TI  - Microbiological properties of poultry breast meat treated with high-intensity
      ultrasound.
AB  - Lactic acid, psychrophilic, and mesophilic bacteria, Escherichia coli, Salmonella
      spp. and Staphylococcus aureus were enumerated on chicken breasts after treatment
      with different high intensity ultrasound (frequency 40 kHz, intensity 9.6 W/cm-2)
      application times (0, 30, and 50 min) and packaging atmospheres (aerobic and
      vacuum) after a 7-day storage. The experiment was performed in commercial 7-week
      old chicken breasts. Counts were performed prior to and immediately after
      ultrasonication, and on the 7th day of chill-storage. After sonication and
      storage, mesophiles, psychrophiles, LAB and S. aureus increased statistically.
      Psychrophiles decreased significantly under anaerobic packaging. There were no
      differences among ultrasonication times in terms of mesophiles, psychrophiles,
      LAB, E. coli and Salmonella spp. S. aureus numbers had a significant reduction
      after 50 min sonication. Under these experimental conditions, high-intensity
      ultrasound for 50 min is a control method of S. aureus and the anaerobic
      packaging reduces numbers of psychrophiles in chicken breast. The effect of
      ultrasound is only significant after the storage time.

PMID- 29361331
TI  - Damage assessment in composite laminates via broadband Lamb wave.
AB  - Time of flight (ToF) based method for damage detection using Lamb waves is widely
      used. However, due to the energy dissipation of Lamb waves and the non-ignorable
      size of damage in composite structure, the performance of damage detection is
      restricted. The objective of this research is to establish an improved method to
      locate and assess damages in composite structure. To choose appropriate
      excitation parameters, the propagation characters of Lamb waves in quasi
      isotropic composite laminates are firstly studied and the broadband excitation is
      designed. Subsequently, the pulse compression technique is adopted for energy
      concentration and high-accuracy distance estimation. On this basis, the gravity
      center of intersections of path loci is employed for damage localization and the
      convex envelop of identified damage edge points is taken for damage contour
      estimation. As a result, both damage location and size can be evaluated, thereby
      providing the information for quantitative damage detection. The experiment
      consisting of five different sizes of damage is carried for method verification
      and the identified results show the efficiency of the proposed method.

PMID- 29361332
TI  - Safety and efficacy of immunotherapy with the recombinant B-cell epitope-based
      grass pollen vaccine BM32.
AB  - BACKGROUND: BM32 is a grass pollen allergy vaccine based on recombinant fusion
      proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4
      major grass pollen allergens and the hepatitis B preS protein. OBJECTIVE: We
      sought to study the safety and clinical efficacy of immunotherapy (allergen
      immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and
      controlled asthma. METHODS: A double-blind, placebo-controlled, multicenter
      allergen immunotherapy field study was conducted for 2 grass pollen seasons.
      After a baseline season, subjects (n = 181) were randomized and received 3
      preseasonal injections of either placebo (n = 58) or a low dose (80 MUg, n = 60)
      or high dose (160 MUg, n = 63) of BM32 in year 1, respectively, followed by a
      booster injection in autumn. In the second year, all actively treated subjects
      received 3 preseasonal injections of the BM32 low dose, and placebo-treated
      subjects continued with placebo. Clinical efficacy was assessed by using combined
      symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of
      Life Questionnaires, and asthma symptom scores. Adverse events were graded
      according to the European Academy of Allergy and Clinical Immunology. Allergen
      specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP
      ISAC. RESULTS: Although statistical significance regarding the primary end point
      was not reached, BM32-treated subjects, when compared with placebo-treated
      subjects, showed an improvement regarding symptom medication, visual analog
      scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom
      scores in both treatment years. This was accompanied by an induction of allergen
      specific IgG without induction of allergen-specific IgE and a reduction in the
      seasonally induced increase in allergen-specific IgE levels in year 2. In the
      first year, more grade 2 reactions were observed in the active (n = 6) versus
      placebo (n = 1) groups, whereas there was almost no difference in the second
      year. CONCLUSIONS: Injections of BM32 induced allergen-specific IgG, improved
      clinical symptoms of seasonal grass pollen allergy, and were well tolerated.

PMID- 29361333
TI  - Specific IgE to gelatin as a cause of anaphylaxis to zoster vaccine.

PMID- 29361334
TI  - Progress in clinical research in surgery and IDEAL.
AB  - The quality of clinical research in surgery has long attracted criticism. High
      quality randomised trials have proved difficult to undertake in surgery, and many
      surgical treatments have therefore been adopted without adequate supporting
      evidence of efficacy and safety. This evidence deficit can adversely affect
      research funding and reimbursement decisions, lead to slow adoption of
      innovations, and permit widespread adoption of procedures that offer no benefit,
      or cause harm. Improvement in the quality of surgical evidence would therefore be
      valuable. The Idea, Development, Exploration, Assessment, and Long-term Follow-up
      (IDEAL) Framework and Recommendations specify desirable qualities for surgical
      studies, and outline an integrated evaluation pathway for surgery, and similar
      complex interventions. We used the IDEAL Recommendations to assess methodological
      progress in surgical research over time, assessed the uptake and influence of
      IDEAL, and identified the challenges to further methodological progress.
      Comparing studies from the periods 2000-04 and 2010-14, we noted apparent
      improvement in the use of standard outcome measures, adoption of Consolidated
      Standards of Reporting Trials (CONSORT) standards, and assessment of the quality
      of surgery and of learning curves, but no progress in the use of qualitative
      research or reporting of modifications during procedure development. Better
      education about research, integration of rigorous evaluation into routine
      practice and training, and linkage of such work to awards systems could foster
      further improvements in surgical evidence. IDEAL has probably contributed only
      slightly to the improvements described to date, but its uptake is accelerating
      rapidly. The need for the integrated evaluation template IDEAL offers for surgery
      and other complex treatments is becoming more widely accepted.

PMID- 29361336
TI  - A new powerful drug to combat river blindness.

PMID- 29361337
TI  - The Effect of a Voice Therapy Program Based on the Taxonomy of Vocal Therapy in
      Women with Behavioral Dysphonia.
AB  - OBJECTIVE: This study aims to propose and analyze the effect of a voice therapy
      program (VTP) in women with behavioral dysphonia. MATERIALS AND METHODS: This is
      a controlled, blinded, and nonrandomized cohort study. Participants of this study
      were 22 women with behavioral dysphonia divided into two groups: G1, 11 women
      with behavioral dysphonia who received the VTP, and G2, 11 women with behavioral
      dysphonia who did not receive any intervention. Before and after 6 weeks, the
      outcome variables evaluated in both groups were auditory-perceptual evaluation of
      the global degree of vocal quality (vowel /a/ and counting), instrumental
      acoustic parameters, Voice-Related Quality of Life, vocal and larynx symptoms,
      and musculoskeletal pain. The statistical analysis used the Wilcoxon, chi-square,
      and Mann-Whitney tests (P < 0.05). RESULTS: After 6 weeks, we observed a
      significantly higher improvement in the general degree of vocal deviation in
      vowels, a reduced F0 and symptom of "fatigue while talking" in G1, and an
      increased "shoulder" pain intensity in G2. Both groups showed improvement in the
      socioemotional domain of Voice-Related Quality of Life. In addition, the
      comparison between the groups showed a significantly greater reduction in
      fundamental frequency and the "voice loss" symptom in G1 compared with G2.
      CONCLUSIONS: The VTP using semioccluded vocal tract exercises obtained a positive
      effect on voice quality, symptoms, and musculoskeletal pain in women with
      behavioral dysphonia. The proposal, based on the taxonomy of voice therapy, seems
      to have promoted a phonatory balance, muscle relaxation, and improvement in the
      vocal resistance of this population.

PMID- 29361335
TI  - Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in
      Ghana, Liberia, and the Democratic Republic of the Congo: a randomised,
      controlled, double-blind phase 3 trial.
AB  - BACKGROUND: The morbidity and socioeconomic effects of onchocerciasis, a
      parasitic disease that is primarily endemic in sub-Saharan Africa, have motivated
      large morbidity and transmission control programmes. Annual community-directed
      ivermectin treatment has substantially reduced prevalence. Elimination requires
      intensified efforts, including more efficacious treatments. We compared
      parasitological efficacy and safety of moxidectin and ivermectin. METHODS: This
      double-blind, parallel group, superiority trial was done in four sites in Ghana,
      Liberia, and the Democratic Republic of the Congo. We enrolled participants (aged
      >=12 years) with at least 10 Onchocerca volvulus microfilariae per mg skin who
      were not co-infected with Loa loa or lymphatic filariasis microfilaraemic.
      Participants were randomly allocated, stratified by sex and level of infection,
      to receive a single oral dose of 8 mg moxidectin or 150 MUg/kg ivermectin as
      overencapsulated oral tablets. The primary efficacy outcome was skin
      microfilariae density 12 months post treatment. We used a mixed-effects model to
      test the hypothesis that the primary efficacy outcome in the moxidectin group was
      50% or less than that in the ivermectin group. The primary efficacy analysis
      population were all participants who received the study drug and completed 12
      month follow-up (modified intention to treat). This study is registered with
      ClinicalTrials.gov, number NCT00790998. FINDINGS: Between April 22, 2009, and Jan
      23, 2011, we enrolled and allocated 998 participants to moxidectin and 501
      participants to ivermectin. 978 received moxidectin and 494 ivermectin, of which
      947 and 480 were included in primary efficacy outcome analyses. At 12 months,
      skin microfilarial density (microfilariae per mg of skin) was lower in the
      moxidectin group (adjusted geometric mean 0.6 [95% CI 0.3-1.0]) than in the
      ivermectin group (4.5 [3.5-5.9]; difference 3.9 [3.2-4.9], p<0.0001; treatment
      difference 86%). Mazzotti (ie, efficacy-related) reactions occurred in 967 (99%)
      of 978 moxidectin-treated participants and in 478 (97%) of 494 ivermectin-treated
      participants, including ocular reactions (moxidectin 113 [12%] participants and
      ivermectin 47 [10%] participants), laboratory reactions (788 [81%] and 415
      [84%]), and clinical reactions (944 [97%] and 446 [90%]). No serious adverse
      events were considered to be related to treatment. INTERPRETATION: Skin
      microfilarial loads (ie, parasite transmission reservoir) are lower after
      moxidectin treatment than after ivermectin treatment. Moxidectin would therefore
      be expected to reduce parasite transmission between treatment rounds more than
      ivermectin could, thus accelerating progress towards elimination. FUNDING:
      UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in
      Tropical Diseases.

PMID- 29361338
TI  - Voice Tremor Outcomes of Subthalamic Nucleus and Zona Incerta Deep Brain
      Stimulation in Patients With Parkinson Disease.
AB  - OBJECTIVES: We aimed to study the effect of deep brain stimulation (DBS) in the
      subthalamic nucleus (STN) and caudal zona incerta (cZi) on level of perceived
      voice tremor in patients with Parkinson disease (PD). STUDY DESIGN: This is a
      prospective nonrandomized design with consecutive patients. METHODS: Perceived
      voice tremor was assessed in patients with PD having received either STN-DBS (8
      patients, 5 bilateral and 3 unilateral, aged 43.1-73.6 years; median = 61.2
      years) or cZi-DBS (14 bilateral patients, aged 39.0-71.9 years; median = 56.6
      years) 12 months before the assessment. Sustained vowels that were produced OFF
      and ON stimulation (with simultaneous l-DOPA medication) were assessed
      perceptually in terms of voice tremor by two raters on a four-point rating scale.
      The assessments were repeated five times per sample and rated in a blinded and
      randomized procedure. RESULTS: Three out of the 22 patients (13%) were concluded
      to have voice tremor OFF stimulation. Patients with PD with STN-DBS showed mild
      levels of perceived voice tremor OFF stimulation and a group level improvement.
      Patients with moderate/severe perceived voice tremor and cZi-DBS showed marked
      improvements, but there was no overall group effect. Six patients with cZi-DBS
      showed small increases in perceived voice tremor severity. CONCLUSIONS: STN-DBS
      decreased perceived voice tremor on a group level. cZi-DBS decreased perceived
      voice tremor in patients with PD with moderate to severe preoperative levels of
      the symptom.

PMID- 29361339
TI  - ADHD, CD, and ODD: Systematic review of genetic and environmental risk factors.
AB  - This review aims to analyze the relationships between Attention-Deficit
      Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Conduct
      Disorder (CD), particularly regarding the relative importance of genetic and
      environmental factors in the development of these disorders. Studies that
      examined at least two of these disorders were obtained from multiple databases,
      following the procedures of the Cochrane Collaboration initiative. Of the 279
      documents obtained, nine were retained for in-depth analysis and were considered
      eligible for inclusion. In addition, eight studies from the manual search were
      included. The objectives, methodological aspects (sample and instruments), and
      the main conclusions were extracted from each study. Overall, the results suggest
      that (a) the causes for the onset and maintenance of these disorders are more
      associated with genetic factors than environmental factors, although the
      importance of the latter is recognized, and (b) children with ADHD have a
      predisposition to manifest behaviors that are common to ODD and CD, including the
      antisocial behavior that these children often display.

PMID- 29361340
TI  - Multiple supervised residual network for osteosarcoma segmentation in CT images.
AB  - Automatic and accurate segmentation of osteosarcoma region in CT images can help
      doctor make a reasonable treatment plan, thus improving cure rate. In this paper,
      a multiple supervised residual network (MSRN) was proposed for osteosarcoma image
      segmentation. Three supervised side output modules were added to the residual
      network. The shallow side output module could extract image shape features, such
      as edge features and texture features. The deep side output module could extract
      semantic features. The side output module could compute the loss value between
      output probability map and ground truth and back-propagate the loss information.
      Then, the parameters of residual network could be modified by gradient descent
      method. This could guide the multi-scale feature learning of the network. The
      final segmentation results were obtained by fusing the results output by the
      three side output modules. A total of 1900 CT images from 15 osteosarcoma
      patients were used to train the network and a total of 405 CT images from another
      8 osteosarcoma patients were used to test the network. Results indicated that
      MSRN enabled a dice similarity coefficient (DSC) of 89.22%, a sensitivity of
      88.74% and a F1-measure of 0.9305, which were larger than those obtained by fully
      convolutional network (FCN) and U-net. Thus, MSRN for osteosarcoma segmentation
      could give more accurate results than FCN and U-Net.

PMID- 29361341
TI  - Quality of life and psychological symptoms in patients with pulmonary
      hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) has a delay in diagnosis that
      makes time since diagnosis of interest in this population. OBJECTIVES: To assess
      psychological conditions, perceived stress, QOL, and interpersonal support and to
      explore whether these factors may correlate with time since diagnosis in patients
      with PAH. METHODS: Participants at an academic medical center (n = 108) completed
      psychological questionnaires (Cambridge Pulmonary Hypertension Outcome Review,
      Patient Health Questionnaire-9, Perceived Stress Scale-10, and Interpersonal
      Support Evaluation List-Short Form). RESULTS: Prevalence of psychiatric disorder,
      major depression, and "other depressive disorder" were 29.6%, 15.7%, and 9.3%,
      respectively. Participants reported adequate social support, high perceived
      stress, and average quality of life. Time since diagnosis was positively
      associated with greater perceived social support (rho = 0.174, p = .075) and
      greater perceived stress (rho = 0.191, p = .048), but no other psychological
      factor. CONCLUSIONS: Routine psychological assessment and timely referral for
      mental health services are suggested. Social support may buffer patients from
      stress.

PMID- 29361342
TI  - Trajectories of BMI change impact glucose and insulin metabolism.
AB  - BACKGROUND AND AIMS: The aim of this study was to examine, in a community
      setting, whether trajectory of weight change over twelve years is associated with
      glucose and insulin metabolism at twelve years. METHODS AND RESULTS: Participants
      were 532 community-living middle-aged and elderly adults from the Personality and
      Total Health (PATH) Through Life study. They spanned the full weight range
      (underweight/normal/overweight/obese). Latent class analysis and multivariate
      generalised linear models were used to investigate the association of Body Mass
      Index (BMI, kg/m2) trajectory over twelve years with plasma insulin (MUlU/ml),
      plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at
      follow-up. All models were adjusted for age, gender, hypertension, pre-clinical
      diabetes status (normal fasting glucose or impaired fasting glucose) and physical
      activity. Four weight trajectories were extracted; constant normal (mean baseline
      BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up
      BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease
      (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI,
      individuals in the constant high and increase trajectories had significantly
      higher plasma insulin, greater insulin resistance, and higher beta cell function
      than those in the constant normal trajectory. Individuals in the decrease
      trajectory did not differ from the constant normal trajectory. Current BMI
      significantly interacted with preceding BMI trajectory in its association with
      plasma insulin, insulin resistance, and beta cell function. CONCLUSION: The
      trajectory of preceding weight has an independent effect on blood glucose
      metabolism beyond body weight measured at any given point in time.

PMID- 29361343
TI  - Three-season effectiveness of inactivated influenza vaccine in preventing
      influenza illness and hospitalization in children in Japan, 2013-2016.
AB  - OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza
      vaccine (IIV) in children 6 months to 15 years of age in 2015/16 season. In
      addition, based on the data obtained during the three seasons from 2013 to 2016,
      we estimated the three-season VE in preventing influenza illness and
      hospitalization. METHODS: Our study was conducted according to a test-negative
      case-control design (TNCC) and as a case-control study based on influenza rapid
      diagnostic test results. RESULTS: During 2015/16 season, the quadrivalent IIV was
      first used in Japan. The adjusted VE in preventing influenza illness was 49% (95%
      confidence interval [CI]: 42-55%) against any type of influenza, 57% (95% CI: 50
      63%) against influenza A and 34% (95% CI: 23-44%) against influenza B. The 3
      season adjusted VE was 45% (95% CI: 41-49%) against influenza virus infection
      overall (N = 12,888), 51% (95% CI: 47-55%) against influenza A (N = 10,410), and
      32% (95% CI: 24-38%) against influenza B (N = 9232). An analysis by age groups
      showed low or no significant VE in infants or adolescents. By contrast, VE was
      highest in the young group (1-5 years old) and declined with age thereafter. The
      3-season adjusted VE in preventing hospitalization as determined in a case
      control study was 52% (95% CI: 42-60%) for influenza A and 28% (95% CI: 4-46%)
      for influenza B, and by TNCC design, it was 54% (95% CI: 41-65%) for influenza A
      and 34% (95% CI: 6-54%) for influenza B. CONCLUSION: We demonstrated not only VE
      in preventing illness, but also VE in preventing hospitalization based on much
      larger numbers of children than previous studies.

PMID- 29361345
TI  - [Refusal of somatic care and delirium: How to reconcile medical duty with the
      right of the patient?]

PMID- 29361344
TI  - Immunogenicity of HPV prophylactic vaccines: Serology assays and their use in HPV
      vaccine evaluation and development.
AB  - When administered as standard three-dose schedules, the licensed HPV prophylactic
      vaccines have demonstrated extraordinary immunogenicity and efficacy. We
      summarize the immunogenicity of these licensed vaccines and the most commonly
      used serology assays, with a focus on key considerations for one-dose vaccine
      schedules. Although immune correlates of protection against infection are not
      entirely clear, both preclinical and clinical evidence point to neutralizing
      antibodies as the principal mechanism of protection. Thus, immunogenicity
      assessments in vaccine trials have focused on measurements of antibody responses
      to the vaccine. Non-inferiority of antibody responses after two doses of HPV
      vaccines separated by 6 months has been demonstrated and this evidence supported
      the recent WHO recommendations for two-dose vaccination schedules in both boys
      and girls 9-14 years of age. There is also some evidence suggesting that one dose
      of HPV vaccines may provide protection similar to the currently recommended two
      dose regimens but robust data on efficacy and immunogenicity of one-dose vaccine
      schedules are lacking. In addition, immunogenicity has been assessed and reported
      using different methods, precluding direct comparison of results between
      different studies and vaccines. New head-to-head vaccine trials evaluating one
      dose immunogenicity and efficacy have been initiated and an increase in the
      number of trials relying on immunobridging is anticipated. Therefore,
      standardized measurement and reporting of immunogenicity for the up to nine HPV
      types targeted by the current vaccines is now critical. Building on previous HPV
      serology assay standardization and harmonization efforts initiated by the WHO HPV
      LabNet in 2006, new secondary standards, critical reference reagents and testing
      guidelines will be generated as part of a new partnership to facilitate
      harmonization of the immunogenicity testing in new HPV vaccine trials.

PMID- 29361346
TI  - Novel Antibiotic-Loaded Cement Femoral Head Spacer for the Treatment of Advanced
      Pyogenic Arthritis in Adult Hip.
AB  - BACKGROUND: The aim of this study is to present a treatment for end-stage
      pyogenic arthritis of the hip using a novel cement spacer. This spacer caused
      less damage to the proximal femoral bone and made the conversion to total hip
      arthroplasty (THA) more convenient while maintaining the advantages of current
      cement spacers loaded with antibiotics. METHODS: We retrospectively reviewed 10
      consecutive cases of hip pyogenic arthritis with joint destruction. These cases
      occurred from September 2009 to June 2015. In these cases, we used an antibiotic
      loaded, cement spacer that was formed in the shape of the femoral head. This
      spacer rested on multiple screws that were inserted in the remaining neck of the
      femur. Once the infection subsided, a conversion to THA was performed in all
      cases. Evaluation included clinical and radiologic outcomes and the development
      of complications. RESULTS: The mean interval between spacer insertion and
      conversion to THA was 101.6 days (range, 59-187 days). The mean follow-up period
      from initial spacer insertion was 44.9 months (range, 15-95 months). All cases
      underwent noncemented THA following the resolution of the initial infection. The
      mean Harris Hip Scores at initial visit, before conversion to THA, and on final
      follow-up were 58.8, 71.0, and 92.5, respectively. No case had any spacer-related
      complications, recurrence of infection, or dislocation. CONCLUSION: The treatment
      of advanced pyogenic arthritis with this novel femoral head spacer technique
      significantly reduced pain, preserved proximal femoral bone and soft tissue
      tension, controlled infection, improved function, and allowed for easier
      conversion to THA.

PMID- 29361348
TI  - Efficacy of Trunk Regimes on Balance, Mobility, Physical Function, and Community
      Reintegration in Chronic Stroke: A Parallel-Group Randomized Trial.
AB  - OBJECTIVE: The study objective was to examine the efficacy of plinth and Swiss
      ball-based trunk exercise regimes on balance, mobility, physical function, and
      community reintegration compared with standard physiotherapy in chronic stroke.
      SUBJECTS AND METHODS: This observer-blinded parallel-group randomized trial was
      conducted in outpatient stroke units. People with chronic stroke aged between 30
      and 75 years, first onset of unilateral cortical lesion, poor trunk performance,
      10 m independent walking ability with or without walking aids, and absence of
      pusher syndrome were included. Trunk Impairment Scale 2.0, Brunel Balance
      Assessment, Tinetti scale, gait speed, Stroke Impact Scale-16, and Reintegration
      to Normal Living Index were the measures. Experimental interventions involved the
      practice of selective upper and lower trunk movements using either plinth or
      Swiss ball. Control group received standard physiotherapy. All the patients
      practiced 1 hour exercise session, 3 sessions a week over a duration of 6 weeks
      and followed up after 3 and 12 months. RESULTS: Of 108 patients allocated into 3
      groups, baseline characteristics were similar. Postintervention compared with
      control group, the plinth, and Swiss ball groups showed significant mean changes
      in the outcome measures: trunk impairment scale 2.0 (3.6;4.1 points), Brunel
      Balance Assessment (1-level), Tinetti scale (5;5.2 points), gait speed (.06;.08
      m/s), Stroke Impact Scale-16 (8.7;7.2 points), and community reintegration
      (7.6;8.8 points). These improvements were retained during 3-12 months' follow-up.
      Statistical significant was set at P < .05. CONCLUSION: Plinth and Swiss ball
      based trunk exercise regimes showed significant improvements in balance,
      mobility, physical function, and community reintegration in chronic stroke as
      against standard physiotherapy.

PMID- 29361349
TI  - Copper removal and microbial community analysis in single-chamber microbial fuel
      cell.
AB  - In this study, copper removal and electricity generation were investigated in a
      single-chamber microbial fuel cell (MFC). Result showed that copper was
      efficiently removed in the membrane-less MFC with removal efficiency of 98.3% at
      the tolerable Cu2+ concentration of 12.5 mg L-1, the corresponding open circuit
      voltage and maximum power density were 0.78 V and 10.2 W m-3, respectively. The
      mechanism analysis demonstrated that microbial electrochemical reduction
      contributed to the copper removal with the products of Cu and Cu2O deposited at
      biocathode. Moreover, the microbial community analysis indicated that microbial
      communities changed with different copper concentrations. The dominant phyla were
      Proteobacteria and Bacteroidetes which could play key roles in electricity
      generation, while Actinobacteria and Acidobacteria were also observed which were
      responsible for Cu-resistant and copper removal. It will be of important guiding
      significance for the recovery of copper from low concentration wastewater through
      single-chamber MFC with simultaneous energy recovery.

PMID- 29361347
TI  - Preliminary mapping of the structural effects of age in pediatric bipolar
      disorder with multimodal MR imaging.
AB  - This study investigates multimodal structural MR imaging biomarkers of
      development trajectories in pediatric bipolar disorder. T1-weighted and diffusion
      weighted MR imaging was conducted to investigate cross-sectional group
      differences with age between typically developing controls (N = 26) and youths
      diagnosed with bipolar disorder (N = 26). Region-based analysis was used to
      examine cortical thickness of gray matter and diffusion tensor parameters in
      superficial white matter, and tractography-based analysis was used to examine
      deep white matter fiber bundles. Patients and controls showed significantly
      different maturation trajectories across brain areas; however, the magnitude of
      differences varied by region. The rate of cortical thinning with age was greater
      in patients than controls in the left frontal pole. While controls showed
      increasing fractional anisotropy (FA) and axial diffusivity (AD) with age,
      patients showed an opposite trend of decreasing FA and AD with age in fronto
      temporal-striatal regions located in both superficial and deep white matter. The
      findings support fronto-temporal-striatal alterations in the developmental
      trajectories of youths diagnosed with bipolar disorder, and further, show the
      value of multimodal computational techniques in the assessment of
      neuropsychiatric disorders. These preliminary results warrant further
      investigation into longitudinal changes and the effects of treatment in the brain
      areas identified in this study.

PMID- 29361350
TI  - A decrease of ATP production steered by PEDF in cardiomyocytes with oxygen
      glucose deprivation is associated with an AMPK-dependent degradation pathway.
AB  - AIMS: The activated AMP activated protein kinase (AMPK) serves as a transient
      protective cardiovascular kinase via preserving adenosine triphosphate (ATP)
      production under ischemic conditions. However, recent studies reveal that
      inhibition of AMPK in stroke is neuroprotection. Pigment epithelium derived
      factor (PEDF) is also known for the protection of ischemic cardiomyocytes.
      However, the relationship between PEDF and AMPK in cardiomyocytes is poorly
      understood. METHODS AND RESULTS: Rat neonatal and adult left ventricular
      cardiomyocytes were isolated and subjected to oxygen-glucose deprivation (OGD).
      During OGD, PEDF significantly reduced AMPKalpha levels to decrease ATP
      production and reduced ATP expenditure both in neonatal and adult cardiomyocytes,
      which increased energy reserves and cell viability. Importantly, pharmacological
      AMPK inhibitor reduced ATP production but failed to decrease ATP expenditure,
      thus leading cells into death. Furthermore, AMPKalpha was degraded by a ubiquitin
      dependent proteasomal degradation pathway, which is associated with a
      PEDF/PEDFR/peroxisome proliferator activated receptor gamma (PPARgamma) axis.
      Inhibition of PPARgamma or proteasome disrupted the interaction of AMPKalpha and
      PPARgamma, which abolished AMPKalpha degradation. Importantly, the decrease of
      AMPKalpha and ATP level was normalized after recovery of oxygen and glucose.
      CONCLUSIONS: We demonstrate a novel mechanism for regulation of cardiac ATP
      production by PEDF involving AMPKalpha and PPARgamma. PEDF promotes proteasomal
      degradation of AMPK and, subsequently, reduces ATP production. The reduction of
      ATP production associated with the decrease of ATP expenditure completed by PEDF
      increase energy reserves and reduces cell energy failure, prolonging the cell
      activity during OGD.

PMID- 29361351
TI  - Power of resting echocardiographic measurements to classify pulmonary
      hypertension patients according to European society of cardiology exercise
      testing risk stratification cut-offs.
AB  - BACKGROUND: Right ventricular function is the major determinant of morbidity and
      mortality in pulmonary arterial hypertension (PAH). The ESC risk assessment
      strategy for PAH is based on clinical status, exercise testing, NTproBNP, imaging
      and haemodynamics but does not include right ventricular function. Our aims were
      to test the power of resting echocardiographic measurements to classify PAH
      patients according to ESC exercise testing risk stratification cut-offs and to
      determine if the classification power of echocardiographic parameters varied in
      chronic thrombo-embolic pulmonary hypertension (CTEPH). METHODS: We prospectively
      and consecutively recruited 46 PAH patients and 42 CTEPH patients referred for
      cardio-pulmonary exercise testing and comprehensive transthoracic
      echocardiography. Exercise testing parameters analyzed were peak oxygen
      consumption, percentage of predicted maximal oxygen consumption and the slope of
      ventilation against carbon dioxide production. Receiver operator characteristic
      curves were used to determine the optimal diagnostic cut-off values of
      echocardiographic parameters for classifying the patients in intermediate or high
      risk category according to exercise testing. RESULTS: Measurements of right
      ventricular systolic function were the best for classifying in PAH (area under
      the curve 0.815 to 0.935). Measurements of right ventricular pressure overload
      (0.810 to 0.909) were optimal for classifying according to exercise testing in
      CTEPH. Measurements of left ventricular function were of no use in either group.
      CONCLUSIONS: Measurements of right ventricular systolic function can classify
      according to exercise testing risk stratification cut-offs in PAH. However, this
      is not the case in CTEPH where pressure overload, rather than right ventricular
      function seems to be linked to exercise performance.

PMID- 29361352
TI  - "PAFIYAMA" syndrome; further evidence on a novel clinical entity.

PMID- 29361353
TI  - Area at risk and collateral circulation in a first acute myocardial infarction
      with occluded culprit artery. STEMI vs non-STEMI patients.
AB  - BACKGROUND: It is unclear why among patients with first acute myocardial
      infarction and an occluded culprit artery only some present ST segment elevation.
      In fact, there is no study that compares the angiographic area at risk and the
      collateral circulation in first NSTEMI vs STEMI patients. METHODS AND RESULTS:
      205 patients admitted for myocardial infarction with occluded culprit artery were
      included, 132 STEMI and 73 NSTEMI. Demographic data, the area at risk determined
      by the BARI score and collateral supply by the Rentrop score from the 2 groups
      were compared. NSTEMI patients showed lower peak Tn I than STEMI in the overall
      group but also in the 3 subsets with different culprit arteries (p < .001). They
      also presented a higher rate of left circumflex coronary artery (CFX) as culprit
      artery (52% vs 14%, p < .001), smaller BARI score area of the culprit artery (5.4
      vs 7.6, p < .001), and higher frequency of well-developed collaterals (Rentrop
      score >= 2, 1.82 vs 0.41, p < .001). The latter was also higher in each of the 3
      different culprit arteries (p = .002-<0.001) Among 38 NSTEMI patients with CFX
      occlusion, 20 with >=1 mm ST depression in V2 to V4 (possible posterior
      infarction) showed a similar Rentrop score than the 18 with other ECG changes but
      lower Tn I peak (p = .012). CONCLUSIONS: In first acute myocardial infarction
      with an occluded culprit artery NSTEMI patients - including those with possible
      posterior infarction - present smaller infarct size and higher collateral blood
      supply than STEMI patients in each of the 3 main culprit arteries.

PMID- 29361354
TI  - Gaze-Evoked Deformations in Optic Nerve Head Drusen: Repetitive Shearing as a
      Potential Factor in the Visual and Vascular Complications.
AB  - PURPOSE: To determine if ocular ductions deform intrapapillary and peripapillary
      tissues in optic nerve head drusen (ONHD) and to compare these deformations with
      healthy eyes and eyes with other optic neuropathies. DESIGN: Observational case
      series. PARTICIPANTS: Twenty patients with ONHD. METHODS: Axial rasters of the
      optic nerve from a spectral-domain OCT device (Cirrus 5000; Carl Zeiss Meditec,
      Inc, Dublin, CA) were used to analyze the shape of the peripapillary basement
      membrane (ppBM) layer in 20 confirmed cases of ONHD. We compared registered
      images obtained from 2 eye positions: 10 degrees  to 15 degrees  in adduction and
      30 degrees  to 40 degrees  in abduction. Geometric morphometrics was used to
      analyze the shape of the ppBM layer defined by placing 10 equidistant landmarks
      extending 2500 MUm on both sides of the basement membrane opening. We also
      adapted an image strain tracking technique to measure regional intrapapillary
      strains in 6 patients. Using manually placed nodes on the reference image (in
      adduction), an iterative, block-matching algorithm is used to determine local
      displacements between the reference and its paired image in abduction.
      Displacement vectors were used to calculate the mean shear and effective strain
      (percent change). MAIN OUTCOME MEASURES: Peripapillary shape deformations,
      intrapapillary shear strains, and effective strains. RESULTS: We found a
      statistically significant difference in the shape of the ppBM layer between
      abduction and adduction (P < 0.01). The deformation was characterized by a
      relative posterior displacement temporally in adduction that reversed in
      abduction. Strain tracking in all 6 patients showed substantial gaze-induced
      shearing and effective strains. Mean effective strains were 7.5% outside the
      drusen. Shear and effective strains were significantly larger outside versus
      within the drusen (P < 0.003 and P < 0.01, respectively). CONCLUSIONS: This study
      demonstrates that horizontal ocular ductions induce significant shearing
      deformations of the peripapillary retina and prelaminar intrapapillary tissues.
      We also found that the deformations in healthy persons are similar in magnitude
      to ONHD. Based on these findings, we speculate that patients with intrapapillary
      calcifications exposed to the long-term effects of repetitive shearing (induced
      by ocular ductions) may contribute to the progressive axonal loss and vascular
      complications associated with ONHD.

PMID- 29361355
TI  - Long-Term Outcomes of Total Exudative Retinal Detachments in Stage 3B Coats
      Disease.
AB  - PURPOSE: To evaluate the long-term outcomes of treatment of total exudative
      retinal detachments (ERDs) secondary to Coats disease (stage 3B) and the role of
      vitrectomy. DESIGN: Retrospective, observational case series. PARTICIPANTS: A
      total of 16 eyes in 16 patients undergoing treatment for total ERDs secondary to
      Coats disease with at least 5 years of follow-up. METHODS: We reviewed the
      records of patients with stage 3B Coats disease. The interventions, including the
      timing of vitrectomy if used, and clinical course were recorded. MAIN OUTCOME
      MEASURES: The primary outcome measures were visual acuity at the most recent
      appointment, whether there was progression to neovascular glaucoma (NVG) or
      phthisis bulbi, and need for enucleation. RESULTS: All patients received ablative
      treatment (photocoagulation or cryotherapy), with 8 having scleral buckling (SB)
      and 6 having external drainage of subretinal fluid (XD). Of the 12 patients who
      had pars plana vitrectomy (PPV), 8 had early PPV (EV) in the first year after
      presenting, and 4 of 8 in the expectant management group had late PPV (late
      vitrectomy) at a mean of 4.3 years post-presentation for treatment of significant
      traction retinal detachment (TRD). The other 4 patients of 8 in the expectant
      management group did not require vitrectomy. Mean follow-up overall was 9 1/2
      years. At the date of last follow-up, 50% had no light perception or light
      perception vision, which was consistent across the subgroups that underwent EV
      (4/8), late vitrectomy (2/4), or no PPV (2/4). A total of 4 of 16 patients had
      progression to NVG or phthisis, 1 of whom required enucleation. CONCLUSIONS: In
      this retrospective series of patients with Stage 3B Coats disease, ablative
      therapy with a combination of PPV, XD, or SB was effective in preventing
      progression to NVG or phthisis in the majority of patients, thus preserving the
      globe. Half of the patients (4/8) in this series who did not undergo PPV in the
      early vitrectomy group developed late-onset TRD, suggesting a possible role for
      early prophylactic vitrectomy with possible SB and XD; however, this is balanced
      by the other half (4/8) in the expectant management group who did not require any
      vitrectomy.

PMID- 29361357
TI  - Genetic Risk Score Is Associated with Vertical Cup-to-Disc Ratio and Improves
      Prediction of Primary Open-Angle Glaucoma in Latinos.
AB  - PURPOSE: Genome-wide association studies have identified multiple genetic
      variants associated with vertical cup-to-disc ratio (VCDR). Genetic risk scores
      (GRS) examine the aggregate genetic effect of individual variants on a trait by
      combining these separate genetic variants into a single measure. The purpose of
      this study was to construct GRS for VCDR and to determine whether the GRS are
      associated with VCDR and whether the GRS increase the discriminatory ability for
      primary open-angle glaucoma (POAG) in a Latino population. DESIGN: Population
      based genetic association study. PARTICIPANTS: A total of 4018 Latino
      participants recruited from Los Angeles. METHODS: Weighted and unweighted GRS
      were constructed using 68 previously reported VCDR single nucleotide
      polymorphisms (SNPs), as well as SNPs from our own genome-wide association data.
      Linear and logistic regression analyses examined the associations of GRS with
      VCDR and POAG, respectively. To evaluate the discriminatory ability of the GRS
      for POAG, we conducted receiver operating characteristic (ROC) analyses. MAIN
      OUTCOME MEASURES: The relationship between GRS and VCDR in Latinos. RESULTS: The
      GRS were associated significantly with VCDR (P < 0.0001), after adjusting for
      age, gender, central corneal thickness, intraocular pressure, and education. The
      weighted GRS explained an additional 2.74% of the variation in VCDR. Adding the
      weighted GRS derived from previously reported SNPs resulted in a moderate
      improvement in the discriminatory ability for POAG during ROC analyses, yielding
      an area under the ROC curve (AUC) of 0.735 (95% CI, 0.701-0.768). When our own
      SNPs were used, the AUC increased significantly to 0.809 (95% CI, 0.781-0.837; P
      < 0.0001). We obtained similar results for the unweighted GRS. CONCLUSIONS: To
      our knowledge, we identified a novel association between GRS and VCDR and its
      improvement in the discriminatory ability of POAG in a Latino population.

PMID- 29361359
TI  - Appropriate methods to define bacteriuria relationship with surgical site
      infection.

PMID- 29361358
TI  - Excess mortality patterns during 1918-1921 influenza pandemic in the state of
      Arizona, USA.
AB  - PURPOSE: Our understanding of the temporal dynamics and age-specific mortality
      patterns of the 1918-1921 influenza pandemic remains scarce due to lack of
      detailed respiratory mortality datasets in the United States and abroad. METHODS:
      We manually retrieved individual death records from Arizona during 1915-1921 and
      applied time series models to estimate the age specific mortality burden of the
      1918-1921 influenza pandemic. We estimated influenza-related excess mortality
      rates and mortality rate ratio increase over baseline based on pneumonia and
      influenza (P&I), respiratory, tuberculosis and all-cause death categories.
      RESULTS: Based on our analysis of 35,151 individual mortality records from
      Arizona, we identified three successive pandemic waves in spring 1918, fall 1918
      winter 1919 and winter 1920. The pandemic associated excess mortality rates per
      10,000 population in Arizona was estimated at 83 for P&I, 86 for respiratory
      causes, 84 for all-causes and 9 for tuberculosis. Age-specific P&I and
      tuberculosis excess death rates were highest among 25- to 44-year-olds and
      individuals >=65 years, respectively. The 25- to 44-year-olds and 5- to 14-year
      olds had highest P&I and tuberculosis mortality impact respectively when
      considering the ratio over background mortality. CONCLUSIONS: The 1918-1921
      influenza pandemic killed an estimated 0.8% of the Arizona population in three
      closely spaced consecutive waves. The mortality impact of the fall 1918 wave in
      Arizona lies in the upper range of previous estimates reported for other US
      settings and Europe, with a telltale age distribution of deaths concentrated
      among young adults. We identified a significant rise in tuberculosis-related
      mortality during the pandemic, lending support to the hypothesis that
      tuberculosis was a risk factor for severe pandemic infection. Our findings add to
      our current understanding of the mortality impact of this pandemic in the US and
      globally.

PMID- 29361360
TI  - Residual bioburden after standard cleaning of the reusable orthopedic depth
      gauge.

PMID- 29361356
TI  - The African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of
      Genotype to Glaucoma Phenotype in African Americans: Study Design and Baseline
      Data.
AB  - PURPOSE: To describe the study protocol and baseline characteristics of the
      African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN: Cross
      sectional, case-control study. PARTICIPANTS: Three thousand two hundred sixty-six
      glaucoma patients and control participants without glaucoma of African or
      European descent were recruited from 5 study centers in different regions of the
      United States. METHODS: Individuals of African descent (AD) and European descent
      (ED) with primary open-angle glaucoma (POAG) and control participants completed a
      detailed demographic and medical history interview. Standardized height, weight,
      and blood pressure measurements were obtained. Saliva and blood samples to
      provide serum, plasma, DNA, and RNA were collected for standardized processing.
      Visual fields, stereoscopic disc photographs, and details of the ophthalmic
      examination were obtained and transferred to the University of California, San
      Diego, Data Coordinating Center for standardized processing and quality review.
      MAIN OUTCOME MEASURES: Participant gender, age, race, body mass index, blood
      pressure, history of smoking and alcohol use in POAG patients and control
      participants were described. Ophthalmic measures included intraocular pressure,
      visual field mean deviation, central corneal thickness, glaucoma medication use,
      or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age
      related macular degeneration, and past cataract surgery, were recorded. RESULTS:
      The 3266 ADAGES III study participants in this report include 2146 AD POAG
      patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control
      participants. The AD POAG patients and control participants were significantly
      younger (both, 67.4 years) than ED POAG patients and control participants (73.4
      and 70.2 years, respectively). After adjusting for age, AD POAG patients had
      different phenotypic characteristics compared with ED POAG patients, including
      higher intraocular pressure, worse visual acuity and visual field mean deviation,
      and thinner corneas (all P < 0.001). Family history of glaucoma did not differ
      between AD and ED POAG patients. CONCLUSIONS: With its large sample size,
      extensive specimen collection, and deep phenotyping of AD and ED glaucoma
      patients and control participants from different regions in the United States,
      the ADAGES III genomics study will address gaps in our knowledge of the genetics
      of POAG in this high-risk population.

PMID- 29361361
TI  - A national survey of interventions and practices in the prevention of blood
      culture contamination and associated adverse health care events.
AB  - The scientific literature indicates that blood culture contamination often leads
      to inappropriate antimicrobial treatment, adverse patient occurrences, and
      potential reporting of false-positive central line-associated bloodstream
      infections. The findings of a national infection prevention survey of blood
      culture practices and related interventions in hospitals support the need for
      infection preventionists to expand their participation in the review of topics
      related to the ordering and collection of blood for culture.

PMID- 29361362
TI  - An exploration of surgical team perceptions toward implementation of surgical
      safety checklists in a non-native English-speaking country.
AB  - BACKGROUND: In-depth information on the success and failure of implementing the
      World Health Organization surgical safety checklist (SSC) has been questioned in
      non-native English-speaking countries. This study explored the experiences of SSC
      implementation and documented barriers and strategies to improve SSC
      implementation. METHODS: A qualitative study was performed in 33 Thai hospitals.
      The information from focus group discussions with 39 nurses and face-to-face, in
      depth interviews with 50 surgical personnel was analyzed using content analysis.
      RESULTS: Major barriers were an unclear policy, inadequate personnel, refusals
      and resistance from the surgical team, English/electronic SSC, and foreign
      patients. The key strategies to improve SSC implementation were found to be
      policy management, training using role-play and station-based deconstruction,
      adapting SSC implementation suitable for the hospital's context, building self
      awareness, and patient involvement. CONCLUSION: The barriers of SSC were related
      to infrastructure and patients. Effective policy management, teamwork and
      individual improvement, and patient involvement may be the keys to successful SSC
      implementation.

PMID- 29361363
TI  - Hand hygiene "hall monitors": Leveraging the Hawthorne effect.
AB  - Unfortunately, more than a decade after the World Health Organization's campaign
      launched, many centers still face challenges with low rates of hand hygiene
      compliance. Several electronic hand hygiene monitoring systems are available, and
      the cost of setup and maintenance varies by institution. At our institution, with
      extremely limited funds for complex interventions, we instead hired a pragmatic
      teenager in search of a summer job and trained her as a hand hygiene "hall
      monitor." We describe an effective, inexpensive intervention that improved our
      unit's hand hygiene performance while also providing youth employment.

PMID- 29361364
TI  - Databases for pediatric surgical health services research.

PMID- 29361365
TI  - Discussion.

PMID- 29361366
TI  - Physiologic levels of resistin induce a shift from proliferation to apoptosis in
      macrophage and VSMC co-culture.
AB  - BACKGROUND: Resistin, an adipokine with inflammatory properties, has been
      associated with plaque vulnerability. Vascular smooth muscle cells and
      macrophages are the major cellular components in advanced atherosclerotic plaques
      and interdependently affect plaque stability. The purpose of this study was to
      examine the effects of resistin on the interactions of vascular smooth muscle
      cells and macrophages using co-culture systems. METHODS: Human monocytes were
      differentiated into macrophages. Vascular smooth muscle cells were grown and
      starved prior to co-culture condition. Indirect co-culture was performed by
      treating macrophages with resistin at 10 ng/mL for 24 hours with/without
      epsilonV1-2, a selective protein kinase C epsilon inhibitor. Macrophages
      supernatants were then used to treat vascular smooth muscle cells for 24 hours.
      Direct co-culture was performed by culturing macrophages and vascular smooth
      muscle cells together for 24 to 48 hours. Cultures were evaluated for changes in
      proliferation, apoptosis, and gene expression of apoptosis, proliferation, and
      inflammation-associated genes. RESULTS: Macrophages induced vascular smooth
      muscle cells proliferation, which was further exaggerated in resistin-treated
      macrophages in the indirect co-culture model. Resistin also upregulated cyclin D1
      and proliferating cell nuclear antigen via protein kinase C epsilon in the
      indirect co-culture. Augmented proliferation was further confirmed in the direct
      co-culture model, particularly at increased macrophage ratios. However, resistin
      treatment induced apoptosis in the presence of direct cell to cell interactions.
      Along with the shift to apoptosis, expressions of caspase 3 and caspase 8 were
      upregulated. The expression of kappa-light-chain-enhancer of activated B cells 1
      and 2 was similar in direct and indirect co-cultures. CONCLUSION: Resistin
      promotes a shift from proliferation to apoptosis in vascular smooth muscle cells
      and macrophage co-culture systems with cellular composition similar to that found
      in vulnerable regions of plaques. Protein kinase C epsilon mediates the effects
      of resistin, suggesting that protein kinase C epsilon may represent a therapeutic
      strategy in resistin-associated atherosclerotic complications.

PMID- 29361367
TI  - Management of the colorectal polyp referred for resection: A case-matched
      comparison of advanced endoscopic surgery and laparoscopic colectomy.
AB  - BACKGROUND: Colonoscopy is the gold standard for colorectal screening and
      surveillance. Advanced endoscopic polypectomy techniques such as endoscopic
      submucosal dissection (ESD) have been introduced to remove large colorectal
      polyps. Our aim was to compare the outcomes of patients who underwent ESD with
      those of who underwent laparoscopic colectomy for benign colorectal polyps.
      METHODS: Patients with a preoperative diagnosis of benign colorectal polyp who
      underwent ESD or colectomy between 2011 and 2016 were case matched for age, sex,
      body mass index, American Society of Anesthesiologists status, polyp size, and
      location. Outcomes and cost data were analyzed. Polyps proximal to the splenic
      flexure were grouped as right-sided polyps, and polyps distal to the splenic
      flexure were grouped as left-sided polyps. RESULTS: We identified 144 patients in
      the laparoscopic resection group and 111 patients in the ESD group; 48 patients
      met the matching criteria. Of the 48 patients in the ESD group, 5 required
      operative resection. Mean duration of stay in laparoscopic resection group and
      the ESD group was 5.2 +/- 2.4 days vs 1.5 +/- 1.4 (P < .001). Mean operative time
      was no different (136 +/- 45 vs 133 +/- 72.7 minutes, respectively). Six patients
      had follow-up colonoscopy within a year in the laparoscopic resection group
      versus 22 patients in the ESD group. The laparoscopic group had 21% complication
      rate versus 15% for the ESD group (P > .05). ESD had a 43% cost-reduction
      advantage over laparoscopic colectomy, with a 44% and 39% cost advantage for
      right- and left-sided lesions, respectively. CONCLUSION: ESD is more cost
      effective than conventional segmental resection. With an experienced endoscopist,
      ESD can be offered as a colon-preserving procedure.

PMID- 29361368
TI  - Predictors for local recurrence and distant metastasis of mucinous colorectal
      adenocarcinoma.
AB  - BACKGROUND: Mucinous adenocarcinoma (MA) is a unique subtype of colorectal
      carcinoma. Although some investigators considered MA a predictor for poor
      prognosis, predictors for poor clinical outcome of MA were not elucidated. The
      present study aimed to investigate the predictors for local recurrence and
      distant metastasis of MA. METHODS: This was a retrospective review of patients
      with MA who underwent operation with curative intent. Variables included patient
      and tumor characteristics, TNM stage, investigations, details of surgery, and
      postoperative outcomes, including local recurrence and distant metastasis.
      Univariate and multivariate regression analyses were performed to determine the
      risk factors for local and systemic disease recurrence. RESULTS: A total of 106
      patients (83 male) of a mean age of 51.5 years were included; 62% of patients had
      colonic tumors, and 38% had rectal tumors; 77% and 58% of colonic and rectal
      cancers, respectively, were T3-T4 tumors. There were no lymph node metastases in
      61% of colonic tumors and 55% of rectal tumors. Local recurrence occurred in 15
      patients (14%) and distant metastasis in 9 (9%). Predictors for local recurrence
      were age (odds ratio [OR]: 1.04; P = .04), female sex (OR: 4.5; P = .01), rectal
      tumors (OR: 3.73; P = .02), and T4 tumors (OR: 10.9; P = 0.03). Predictors for
      distant metastasis were age (OR: 1.1; P = .016), local recurrence (OR: 24.28; P <
      .0001), and T4 tumors (OR: 19.3; P = .049). CONCLUSION: Patients' age, female
      sex, and T4 tumors were significant predictors for local recurrence and distant
      metastasis. Rectal tumors had a greater likelihood for regional recurrence than
      colonic tumors. Local recurrence was an independent risk factor for distant
      metastasis.

PMID- 29361370
TI  - Correlating liver stiffness with disease severity scoring system (DS3) values in
      Gaucher disease type 1 (GD1) patients.
AB  - Gaucher disease (GD) is an autosomal-recessive lysosomal storage disease caused
      by a deficiency of the enzyme, glucocerebrocidase, resulting in accumulation of
      lipid-laden storage cells in multiple organs such as bone marrow, liver, spleen,
      and lungs. Type 1 Gaucher disease is the most common form of this condition in
      which the brain and spinal cord (the central nervous system) are not affected.
      The Gaucher disease severity scoring system (GD-DS3) is typically used to assess
      disease severity accounting for skeletal, hematologic, and visceral disease. In
      addition to being time consuming for the clinician to calculate the scores, some
      of the assessments are subjective and may falsely increase or decrease disease
      severity. The purpose of this study was to determine if there is a correlation
      between liver stiffness values obtained from MR elastography (MRE) and the GD-DS3
      score. An IRB approved, HIPAA compliant retrospective study was performed. All
      patients with type 1 GD imaged with MRE between 2011 and 2016 were included in
      this study. Clinical and imaging data was collected. Two pediatric radiologists
      analyzed MR images from abdomen and thigh studies independently to determine bone
      marrow involvement using a semi-quantitative scoring system with one reviewer
      analyzing a subset of studies to determine inter-observer reliability. The
      collected data was used to calculate a GD-DS3 score for all patients. GD-DS3
      scores were compared with liver MRE stiffness values. Clinical MRE scores were
      plotted against GD-DS3 severity scores for 31 patients (15 males, 16 females;
      median age 27years, age range: 4-67years). The median GD-DS3 score was 4 (range:
      1-10.1) and median MRE value was 2.43kPa (range: 1.30-5.20kPa). A significant
      positive correlation was found between MRE and GD-DS3 scores; Pearson's
      correlation coefficient value of r=0.47, p<0.001 for all scores, r=0.68, p<0.001
      for complete scores and r=0.46, p<0.07 for incomplete scores. The inter-observer
      variation of bone marrow burden showed only fair agreement with a Kappa
      coefficient of 0.26. There is a significant positive correlation between
      increasing liver stiffness and increasing composite GD-DS3 scores. This supports
      the use of MRE, a non-invasive reproducible quantitative test, as both an
      additional assessment and independent marker for monitoring disease severity and
      progression in GD.

PMID- 29361369
TI  - Meloxicam increases epidermal growth factor receptor expression improving
      survival after hepatic resection in diet-induced obese mice.
AB  - BACKGROUND: Patients with fatty liver have delayed regenerative responses,
      increased hepatocellular injury, and increased risk for perioperative mortality.
      Currently, no clinical therapy exists to prevent liver failure or improve
      regeneration in patients with fatty liver. Previously we demonstrated that obese
      mice have markedly reduced levels of epidermal growth factor receptor in liver.
      We sought to identify pharmacologic agents to increase epidermal growth factor
      receptor expression to improve hepatic regeneration in the setting of fatty liver
      resection. METHODS: Lean (20% calories from fat) and diet-induced obese mice (60%
      calories from fat) were subjected to 70% or 80% hepatectomy. RESULTS: Using the
      BaseSpace Correlation Engine of deposited gene arrays we identified agents that
      increased hepatic epidermal growth factor receptor. Meloxicam was identified as
      inducing epidermal growth factor receptor expression across species. Meloxicam
      improved hepatic steatosis in diet-induced obese mice both grossly and
      histologically. Immunohistochemistry and Western blot analysis demonstrated that
      meloxicam pretreatment of diet-induced obese mice dramatically increased
      epidermal growth factor receptor protein expression in hepatocytes. After 70%
      hepatectomy, meloxicam pretreatment ameliorated liver injury and significantly
      accelerated mitotic rates of hepatocytes in obese mice. Recovery of liver mass
      was accelerated in obese mice pretreated with meloxicam (by 26% at 24 hours and
      38% at 48 hours, respectively). After 80% hepatectomy, survival was dramatically
      increased with meloxicam treatment. CONCLUSION: Low epidermal growth factor
      receptor expression is a common feature of fatty liver disease. Meloxicam
      restores epidermal growth factor receptor expression in steatotic hepatocytes.
      Meloxicam pretreatment may be applied to improve outcome after fatty liver
      resection or transplantation with steatotic graft.

PMID- 29361371
TI  - Mass spectrometry analysis reveals differences in the host cell protein species
      found in pseudotyped lentiviral vectors.
AB  - Lentiviral vectors (LVs) have been successfully used in clinical trials showing
      long term therapeutic benefits. Studying the role of cellular proteins in
      lentivirus HIV-1 life cycle can help understand virus assembly and budding,
      leading to improvement of LV production for gene therapy. Lentiviral vectors were
      purified using size exclusion chromatography (SEC). The cellular protein
      composition of LVs produced by two different methods was compared: the transient
      transfection system pseudotyped with the VSV-G envelope, currently used in
      clinical trials, and a stable producer cell system using a non-toxic envelope
      derived from cat endogenous retrovirus RD114, RDpro. Proteins of LVs purified by
      size exclusion chromatography were identified by tandem mass spectrometry
      (MS/MS). A smaller number of cellular protein species were detected in stably
      produced vectors compared to transiently produced vector samples. This may be due
      to the presence of co-purified VSV-G vesicles in transiently produced vectors.
      AHNAK (Desmoyokin) was unique to RDpro-Env vectors. The potential role in LV
      particle production of selected proteins identified by MS analysis including
      AHNAK was assessed using shRNA gene knockdown technique. Down-regulation of the
      selected host proteins AHNAK, ALIX, and TSG101 in vector producer cells did not
      result in a significant difference in vector production.

PMID- 29361372
TI  - Arterial Phantoms with Regional Variations in Wall Stiffness and Thickness.
AB  - Regional wall stiffening and thickening are two common pathological features of
      arteries. To account for these two features, we developed a new arterial phantom
      design framework to facilitate the development of vessel models that contain a
      lesion segment whose wall stiffness and thickness differ from those of other
      segments. This new framework is based on multi-part injection molding principles
      that sequentially casted the lesion segment and the flank segments of the vessel
      model using molding parts devised with computer-aided design tools. The vessel
      mimicking material is created from polyvinyl alcohol cryogel, and its acoustic
      properties are similar to those of arteries. As a case demonstration, we
      fabricated a stenosed three-segment phantom composed of a central lesion segment
      (5.1-mm diameter, 1.95-mm wall thickness, 212.6-kPa elastic modulus) and two
      flank segments (6.0-mm diameter, 1.5-mm wall thickness, 133.7-kPa elastic
      modulus). B-mode imaging confirmed the difference in thickness between the lesion
      segment and flank segments of the phantom. Also, Doppler-based vessel wall
      displacement analysis revealed that when pulsatile flow was fed through the
      phantom (carotid pulse; 27 mL/s peak flow rate), the lesion segment distended
      less compared with the flank segments. Specifically, the three-beat averaged peak
      wall displacement in the lesion segment was measured as 0.28 mm, and it was
      significantly smaller than that of the flank segments (0.60 mm). It is
      anticipated that this new multi-segment arterial phantom can serve as a
      performance testbed for the evaluation of local arterial stiffness estimation
      algorithms.

PMID- 29361374
TI  - Emergency department volunteers: Defining the position and its effect on the
      patient experience.

PMID- 29361375
TI  - Arthroscopic soft-tissue interposition arthroplasty of the glenohumeral joint for
      ochronotic arthropathy: A case report.

PMID- 29361373
TI  - Ultrasound-Mediated Microbubble Destruction Suppresses Melanoma Tumor Growth.
AB  - Melanoma is one of the most aggressive types of cancer, and its incidence has
      increased rapidly in the past few decades. In this study, we investigated a novel
      treatment approach, the use of low-intensity ultrasound (2.3 W/cm2 at 1 MHz)
      mediated Optison microbubble (MB) destruction (UMMD) to treat melanoma in a flank
      tumor model. The effect of UMMD was first evaluated in the melanoma cell line B16
      F10 (B16) in vitro and then in mice inoculated with B16 cells. MB+B16 cells were
      exposed to US in vitro, resulting in significant cell death proportional to duty
      cycle (R2 = 0.74): approximately 30%, 50%, 80% and 80% cell death at 10%, 30%,
      50% and 100% DC respectively. Direct implantation of tumors with MBs, followed by
      sonication, resulted in retarded tumor growth and improved survival (p = 0.0106).
      Immunohistochemical analyses confirmed the significant changes in expression of
      the cell proliferation marker Ki67 (p = 0.037) and a microtubule-associated
      protein 2 (p = 0.048) after US + MB treatment. These results suggest that UMMD
      could be used as a possible treatment approach in isolated melanoma and has the
      potential to translate to clinical trials.

PMID- 29361376
TI  - Diagnosis and treatment of slipped capital femoral epiphysis: Recent trends to
      note.
AB  - : Slipped capital femoral epiphysis (SCFE) is not frequently encountered during
      routine practice and diagnosis and treatment are often delayed. It is important
      to understand symptoms and imaging features to avoid delayed diagnosis. After the
      diagnosis is made correct classification of the disease is required. The
      classification should be based on the physeal stability in order to choose safe
      and effective treatment. However, surgeons should bear in mind that the
      assessment is challenging and actual physeal stability is not always consistent
      with the stability predicted by a clinical classification method. TREATMENT OF
      STABLE SCFE: Closed reduction is not indicated for stable SCFE, where continuity
      between the epiphysis and metaphysis has not been disrupted. Treatment method(s)
      is (are) chosen from in-situ fixation, osteotomy and femoroacetabular impingement
      treatment. A single screw fixation is often used to fix the epiphysis and the
      dynamic method is considered especially for young patients. Traditional three
      dimensional trochanteric osteotomies have been associated with procedural
      complexity and uncertainty. A simpler osteotomy method using an updated imaging
      analysis technology should be considered. Modified-Dunn procedure is indicated
      for a severe stable SCFE. However, caution is required because recent studies
      have reported a high rate of complications including postoperative femoral head
      avascular necrosis (AVN) and hip instability when this method is indicated for
      stable SCFE. TREATMENT OF UNSTABLE SCFE: Treatment of unstable SCFE is difficult
      and complication rate is high. Most of unstable SCFE patients were previously
      treated with closed method and it was difficult to predict an occurrence of
      postoperative AVN. However, treatment of unstable SCFE has gradually changed in
      recent years and many studies have shown that physeal hemodynamics can be
      assessed during treatment. Preoperative assessments include contrast-enhanced MRI
      and bone scintigraphy. Intraoperative assessments include confirmation of
      bleeding after drilling the femoral head and monitoring the intracranial pressure
      by laser doppler flowmetry. It is expected that postoperative AVN can be
      prevented in many cases by performing the treatment while assessing the
      intraoperative physeal hemodynamics. Open surgeries have begun to be indicated in
      the treatment of unstable SCFE through either of anterior approach or (modified)
      Dunn procedure. The authors expect that recent improvements in assessment of
      physeal hemodynamics and open treatment method provide improved clinical outcomes
      in the treatment of SCFE.

PMID- 29361377
TI  - Application of liquid semen technology under the seasonal dairy production system
      in New Zealand.
AB  - Systems for preserving semen in liquid form for artificial insemination were
      developed before cryopreserved semen became widely available in the 1960s.
      Advantages of liquid semen include reduced number of sperm per dose, reduced
      storage and transportation costs, increased insemination speed and safety in the
      field. A liquid semen dose requires one tenth the sperm number in a frozen semen
      dose to achieve equivalent fertility (24 day non-return rate: 67.6% for liquid
      versus 67.8% for frozen). The main disadvantage of liquid semen is its relatively
      short shelf life, thus limiting its application mainly to countries, like New
      Zealand and Ireland, with predominantly seasonal dairy production systems.
      Nevertheless, successful application of liquid semen technology can improve the
      rate of genetic gain by increasing the utilization of elite sires. This brief
      review covers the principles of liquid semen preservation and describes why and
      how this technology is implemented by Livestock Improvement Corporation in New
      Zealand.

PMID- 29361378
TI  - [Use of ITS and ISSR markers in the molecular characterisation of Pleurotus
      djamor hybrid strains].
AB  - BACKGROUND: Molecular characterisation of wild type Pleurotus species is
      important for germplasm conservation and its further use for genetic improvement.
      No molecular studies have been performed with monokaryons used for producing
      hybrid strains, either with the reconstituted strains obtained by pairing those
      monokaryons. The molecular characterisation of parental dikaryons, hybrid, and
      reconstituted strains as well as monokaryotic strains, is therefore of utmost
      importance. AIMS: To carry out the molecular identification of Pleurotus djamor
      strains, i.e. dikaryotic wild type strains, hybrid strains, and the monokaryotic
      strains used for the hybrid formation. METHODS: Five wild type strains of P.
      djamor from different states in Mexico were collected and molecularly identified
      by sequencing the ITS1-5.8-ITS2 region using ITS1 and ITS4 universal
      oligonucleotides. Four hybrid strains were obtained by pairing neohaplonts of two
      wild type strains selected. Six ISSR markers were used for the molecular
      characterisation of monokaryotic and dikaryotic strains. RESULTS: Using the ITS
      markers, an amplified product of 700bp was obtained in five wild type strains,
      with a 99-100% similarity with P. djamor. A total of 95 fragments were obtained
      using the ISSR markers, with 99% of polymorphism. CONCLUSIONS: Wild type strains
      were identified as P. djamor, and were clearly grouped with Mexican strains from
      other states of Mexico. ISSR markers allowed the generation of polymorphic bands
      in monokaryotic and dikaryotic strains, splitting both types of strains. The high
      degree of polymorphism indicates the genetic diversity of P. djamor, an advantage
      in mushroom production and in the improving of the species.

PMID- 29361379
TI  - A novel homozygous MFN2 mutation associated with severe and atypical CMT2
      phenotype.
AB  - BACKGROUND: Charcot-Marie-Tooth (CMT) neuropathies represent the most common
      forms of inherited polyneuropathies. CMT2A, the axonal form, accounts for about
      one third of all CMT cases. Variants in the MFN2 gene have been recognized to be
      a major cause of CMT2A. To date, more than 100 pathogenetic mutations in MFN2
      have been identified, leading to different neurological clinical spectrum,
      varying from hereditary neuropathies to more severe clinical phenotypes.
      Pathogenic variants in MFN2 mainly act in a dominant manner, although in a few
      sporadic or familial cases, homozygous or compound heterozygous mutations have
      been reported. RESULTS: We describe a child carrying a novel homozygous MFN2
      mutation leading to an early-onset sensorimotor axonal neuropathy with an
      atypical and severe phenotype. CONCLUSION: The case highlights a very rare
      mechanism of inheritance for MFN2 mutations and expands the clinical and allelic
      variance of severe CMT2A phenotype. Moreover, it proposes the involvement of
      cerebellar peduncles observed at neuroimaging as a novel clue to suspect the
      diagnosis and address genetic testing.

PMID- 29361380
TI  - Interleukin-6: A promising cytokine to support liver regeneration and adaptive
      immunity in liver pathologies.
AB  - Liver pathologies (fibrosis, cirrhosis, alcoholic, non-alcoholic diseases and
      hepatocellular carcinoma) represent one of the most common causes of death
      worldwide. A number of genetic and environmental factors contribute to the
      development of liver diseases. Interleukin-6 (IL-6) is a pleiotropic cytokine,
      exerting variety of effects on inflammation, liver regeneration, and defence
      against infections by regulating adaptive immunity. Due to its high abundance in
      inflammatory settings, IL-6 is often viewed as a detrimental cytokine. However,
      accumulating evidence supports the view that IL-6 has a beneficial impact in
      numerous liver pathologies, due to its roles in liver regeneration and in
      promoting an anti-inflammatory response in certain conditions. IL-6 promotes
      proliferation, angiogenesis and metabolism, and downregulates apoptosis and
      oxidative stress; together these functions are critical for mediating
      hepatoprotection. IL-6 is also an important regulator of adaptive immunity where
      it induces T cell differentiation and regulates autoimmunity. It can augment
      antiviral adaptive immune responses and mitigate exhaustion of T cells during
      chronic infection. This review focuses on studies that present IL-6 as a key
      factor in regulating liver regeneration and in supporting effector immune
      functions and suggests that these functions of IL-6 can be exploited in treatment
      strategies for liver pathologies.

PMID- 29361381
TI  - Drug induced pseudolymphoma.
AB  - Atypical lymphocytic infiltrates of the skin comprise a broad spectrum of
      entities ranging from benign infiltrates to those that are malignant. Many of
      these infiltrates are in fact reactive lymphomatoid ones related to drug therapy
      falling under the general category of drug associated pseudolymphoma. Within this
      nosologic umbrella are nodular and diffuse infiltrates resembling low grade T and
      B cell lymphoma consistent with lymphocytoma cutis, drug associated reversible T
      cell dyscrasias which draw a strong morphologic and phenotypic parallel with
      mycosis fungoides and the various pre-lymphomatous T cell dyscrasias, and
      angiocentric CD30 positive infiltrates mirroring lymphomatoid papulosis. The
      implicated drug classes are quite varied and include antidepressants,
      antihistamines, calcium channel blockers, statins, anticonvulsants, and various
      biologic drugs. The drugs from these various drug classes exert certain effects
      on lymphoid function including evoking overzealous responses to other antigenic
      stimuli. As the adverse effect on lymphocyte function may be cumulative over
      years and or reflect the interplay of other drugs, a temporal association may not
      exist between the onset of the rash/lesion and the initiation of the drug. In
      certain lymphomatoid reactions however such as DRESS syndrome the drug may
      function as both an antigen as well as an immune dysregulating agent. It is
      critical that the pathologist works carefully with the clinician in the
      evaluation of all atypical cutaneous lymphoid infiltrates where the distinction
      between pseudolymphoma versus lymphoma cannot be reliably made based on
      pathologic analysis alone.

PMID- 29361383
TI  - How Primate Brains Vary and Evolve.
AB  - Studies of brain evolution tend to focus on differences across species rather
      than on variation within species. A new study measures and compares intraspecific
      variation in macaque and human brain anatomy to explore the effect that short
      term diversity has on long-term evolution.

PMID- 29361382
TI  - Modeling the Predictive Social Mind.
AB  - The social mind is tailored to the problem of predicting the mental states and
      actions of other people. However, social cognition researchers have only
      scratched the surface of the predictive social mind. We discuss here a new
      framework for explaining how people organize social knowledge and use it for
      social prediction. Specifically, we propose a multilayered framework of social
      cognition in which two hidden layers - the mental states and traits of others -
      support predictions about the observable layer - the actions of others. A
      parsimonious set of psychological dimensions structures each layer, and proximity
      within and across layers guides social prediction. This simple framework
      formalizes longstanding intuitions from social cognition, and in doing so offers
      a generative model for deriving new hypotheses about predictive social cognition.

PMID- 29361384
TI  - Evaluation of endothelial dysfunction, endothelial plasma markers, and
      traditional metabolic parameters in children with adiposity.
AB  - BACKGROUND/PURPOSE: To investigate the correlations among endothelial function
      assessment parameters, asymmetric dimethylarginine (ADMA)-related biomarkers, and
      traditional risk factors in adipose children. METHODS: We enrolled adipose
      children aged 7-18 years between July 2014 and August 2016 as well as normal
      weight controls from the outpatient clinic. Vascular measurements including
      echocardiography, carotid intima media thickness, pulse wave velocity (PWV), and
      flow-mediated dilation (FMD) were measured. Venous blood samples including
      traditional metabolic and endothelial dysfunction parameters were analyzed.
      Participants were grouped as adipose vs. normal-weight and as adipose with
      hypertension vs. adipose without hypertension. Clinical presentations, laboratory
      data, and cardiovascular measurement were compared. RESULTS: Of the 105 enrolled
      children, 85 were adipose. Adipose children had higher systolic blood pressure,
      larger left ventricular (LV) mass, and adverse traditional metabolic biomarkers.
      FMD was significantly reduced (8.25 (5.32-12.06) % vs. 12.49 (7.18-16.58) %, p =
      0.018) in the adipose group. PWV was markedly increased (4.65 (4.2-5.5) m/sec vs.
      3.95 (3.38-4.35) m/sec, p < 0.001) in the hypertensive adipose children.
      Endothelial dysfunction parameters were not significantly changed in this study.
      CONCLUSION: Adipose children were at higher risk of hypertension and LV
      hypertrophy. FMD, PWV and traditional cardiovascular biomarkers can detect subtle
      vascular changes. Hypertension is an important sign of arterial involvement in
      adipose children. Although ADMA-related biomarkers were not statistically
      significant, future studies are needed to confirm its correlation with adiposity
      and hypertension in children. The early detection and prevention of endothelial
      dysfunction may decrease the rate of progression to cardiovascular consequences
      in later life.

PMID- 29361385
TI  - Mutation screening of INS and KCNJ11 genes in Taiwanese children with type 1B
      diabetic onset before the age of 5 years.
AB  - Type 1 diabetes (T1D) is caused by beta-cell destruction, usually leading to
      absolute insulin deficiency. T1D is a heterogeneous disease and is divided into
      two subtypes according to the presence or absence of pancreatic autoantibodies:
      type 1A (immune mediated) and type 1B (idiopathic). Genes such as KCNJ11 or INS,
      which play key roles in beta-cell function, provide some insight into the
      pathogenesis of type 1B diabetes. In this study, we screened 110 Taiwanese
      children (61 males and 49 females) with T1D onset before the age of 5 years for
      mutations of INS and KCNJ11. We identified one missense heterozygous mutation in
      KCNJ11 (c.989A>G, p.Y330C) and no INS mutations among 28 probands. This is the
      first study to screen patients with autoantibody-negative T1D diagnosed before
      the age of 5 years for INS and KCNJ11 mutations in Taiwan. Although KCNJ11
      mutations are always reported in patients with permanent neonatal diabetes, this
      gene mutation can be detected after 6 months of age. Further studies in other
      patients with type 1B diabetes and their families are required to elucidate the
      contributions of the KCNJ11 mutation to the T1D phenotype.

PMID- 29361386
TI  - Wilderness First Responder: Are Skills Soon Forgotten?
AB  - Wilderness first responders are trained to provide competent medical care in
      wilderness settings or until evacuation for more advanced treatment can be
      obtained. In light of the isolated environments in which they are called upon to
      respond to illnesses and injuries, their ability to effectively apply their
      training is crucial. Despite the responsibility assigned to them, there is an
      absence of research assessing the skill and knowledge retention of wilderness
      first responders, creating a gap in understanding whether a deficit in their
      ability to perform exists between certifications. Without such research, it is
      important to review knowledge and skill retention in related responder groups.
      The literature over the past 4 decades documents the loss over time of skills and
      knowledge across an array of trained responders, both professional and laypeople.
      Although the findings reviewed suggest that WFRs will exhibit a similar pattern
      of increasing skill loss beginning shortly after certification and a slower, but
      concurrent, decrease in knowledge, research is needed to document or refute this
      assumption.

PMID- 29361387
TI  - Microangiopathic Hemolytic Anemia Following Three Different Species of Hump-Nosed
      Pit Viper (Genus: Hypnale) Envenoming in Sri Lanka.
AB  - There are 3 species of hump-nosed pit vipers in Sri Lanka: Hypnale hypnale,
      Hypnale zara, and Hypnale nepa. The latter 2 are endemic to the country.
      Microangiopathic hemolytic anemia (MAHA) is a known complication of hump-nosed
      pit viper bites. It was previously documented as a complication of general viper
      bites and not species specific. We report a series of 3 patients who developed
      MAHA after being bitten by each species of hump-nosed pit viper. The first
      patient was bitten by H hypnale and developed a severe form of MAHA associated
      with acute kidney injury and thrombocytopenia falling into the category of
      thrombotic microangiopathy. The other 2 developed MAHA that resolved without any
      complications.

PMID- 29361388
TI  - Quantitative analysis of elevation of serum creatinine via renal transporter
      inhibition by trimethoprim in healthy subjects using physiologically-based
      pharmacokinetic model.
AB  - Serum creatinine (SCr) levels rise during trimethoprim therapy for infectious
      diseases. This study aimed to investigate whether the elevation of SCr can be
      quantitatively explained using a physiologically-based pharmacokinetic (PBPK)
      model incorporating inhibition by trimethoprim on tubular secretion of creatinine
      via renal transporters such as organic cation transporter 2 (OCT2), OCT3,
      multidrug and toxin extrusion protein 1 (MATE1), and MATE2-K. Firstly,
      pharmacokinetic parameters in the PBPK model of trimethoprim were determined to
      reproduce the blood concentration profile after a single intravenous and oral
      administration of trimethoprim in healthy subjects. The model was verified with
      datasets of both cumulative urinary excretions after a single administration and
      the blood concentration profile after repeated oral administration. The
      pharmacokinetic model of creatinine consisted of the creatinine synthesis rate,
      distribution volume, and creatinine clearance (CLcre), including tubular
      secretion via each transporter. When combining the models for trimethoprim and
      creatinine, the predicted increments in SCr from baseline were 29.0%, 39.5%, and
      25.8% at trimethoprim dosages of 5 mg/kg (b.i.d.), 5 mg/kg (q.i.d.), and 200 mg
      (b.i.d.), respectively, which were comparable with the observed values. The
      present model analysis enabled us to quantitatively explain increments in SCr
      during trimethoprim treatment by its inhibition of renal transporters.

PMID- 29361389
TI  - Behavioral addictions in early-onset Parkinson disease are associated with DRD3
      variants.
AB  - BACKGROUND: Impulse control disorders (ICDs) comprise abnormal behaviors
      frequently found in patients with Parkinson's disease (PD) receiving
      antiparkinsonian medication. ICDs in PD would develop when dopaminergic treatment
      overstimulates the dopamine receptor D3 (DR3). Here we studied whether DR3 gene
      (DRD3) is associated to ICD in PD patients with early-onset (EOPD). METHODS: We
      performed association analysis of the rs6280 DRD3 single nucleotide variation
      (SNV) (Ser9Gly) in a clinical sample of 126 non early-onset PD (NEOPD) and 73
      EOPD (age at onset < 45). ICD was evaluated using the Questionnaire for Impulsive
      Compulsive Disorders (QUIP) in PD. RESULTS: In the total sample, we found that a
      younger onset of PD is linked to ICD traits with a potentially addictive
      reinforcement (ICDARs, behavioral addictions) (p = .017) and a trend for total
      ICDs (p = .078) while punding was not associated (p = .75). EOPD sample showed an
      increase of DRD3 C+ genotype for ICD (p = .022) and ICDARs (p = .043) but not for
      punding (p = .170). The post-hoc analyses including the time of evolution and
      Pramipexol or Ropinirole treatments, confirmed the independent effect of the DRD3
      upon ICDs (p = .028) and ICDARs (p = .041) as well as the interaction between
      DRD3 and Pramipexol treatment upon ICDARs (OR = 4.60, 95% CI 1.20-17.632, p =
      .026). The NEOPD group showed no association between DRD3 and ICDs. CONCLUSIONS:
      We found that behavioral addictions in PD are associated with an early onset of
      the disease, the rs6280 DRD3 SNV and the type of dopamine agonist. Further
      investigation in independent samples is warranted.

PMID- 29361390
TI  - Does hot weather affect work-related injury? A case-crossover study in Guangzhou,
      China.
AB  - BACKGROUND: Despite increasing concerns about the health effects of climate
      change, the extent to which workers are affected by hot weather is not well
      documented. This study aims to investigate the association between high
      temperatures and work-related injuries using data from a large subtropical city
      in China. METHODS: We used workers' compensation claims to identify work-related
      injuries in Guangzhou, China during 2011-2012. To feature the heat effect, the
      study period was restricted to the warm seasons in Guangzhou (1 May-31 October).
      We conducted a time-stratified case-crossover study to examine the association
      between ambient outdoor temperatures, including daily maximum and minimum
      temperatures, and cases of work-related injury. The relationships were assessed
      using conditional Poisson regression models. RESULTS: Overall, a total of 5418
      workers' compensation claims were included over the study period. Both maximum
      and minimum temperatures were significantly associated with work-related
      injuries, but associations varied by subgroup. One  degrees C increase in maximum
      temperature was associated with a 1.4% (RR = 1.014, 95%CIs 1.012-1.017) increase
      in daily injury claims. Significant associations were seen for male and middle
      aged workers, workers in small and medium-sized enterprises, and those working in
      manufacturing sector. And 1  degrees C increase in minimum temperature was
      associated with 1.7% (RR = 1.017, 95%CIs 1.012-1.021) increase in daily injury
      claims. Significant associations were observed for female and middle-aged
      workers, workers in large-sized enterprises, and those working in transport and
      construction sectors. CONCLUSIONS: We found a higher risk of work-related
      injuries due to hot weather in Guangzhou, China. This study provides important
      epidemiological evidence for policy-makers and industry that may assist in the
      formulation of occupational safety and climate adaptation strategies.

PMID- 29361391
TI  - Breastfeeding Practices and Opinions of Latina Mothers in an Urban Pediatric
      Office: A Focus Group Study.
AB  - INTRODUCTION: The purpose of this qualitative study was to explore beliefs about
      breastfeeding among Latina mothers. The focus groups were part of a sequential
      mixed methods study. METHODS: Two focus groups were conducted. Participants were
      Spanish-speaking mothers with infants younger than 12 months. Focus groups were
      conducted in Spanish and audiorecorded. The researchers performed open coding of
      the data, compared and converged codes, and identified common themes and
      relationships among the themes. RESULTS: Mothers described concerns about
      adequacy of breastfeeding for their infants' needs, the continued goodness of
      breast milk, and weaning. They expressed lack of knowledge about using breast
      pumps and other assists that could help them breastfeed. DISCUSSION: Culturally
      tailored breastfeeding education and support have not been adequately implemented
      in this urban clinic and likely in other similar settings. More targeted
      attention to this population could improve exclusive breastfeeding of infants and
      ultimately result in better child health.

PMID- 29361392
TI  - Preschool wheeze, genes and treatment.
AB  - Preschool wheeze is a common but poorly understood cause of respiratory morbidity
      that is both distinct from and overlaps with infantile bronchiolitis and school
      age asthma. Attempts at classification by epidemiology, pathophysiology,
      therapeutic response and clinical phenotype are imperfect and yet fundamental to
      both treatment choice and research design. The four main therapeutic classes for
      preschool wheeze, namely beta2 agonists, anticholinergics, corticosteroids and
      leukotriene modifiers are employed with variable and often scanty evidence base,
      with evidence for a genetic influence on response variations. The article will
      discuss the pharmacogenetics of the various options, summarise current treatment
      recommendations, and explore future research directions.

PMID- 29361393
TI  - Complementary and Integrative Health Approaches-Insights and Implications for
      Practice and Research.

PMID- 29361394
TI  - Falls and resulting fractures in Myotonic Dystrophy: Results from a multinational
      retrospective survey.
AB  - Myotonic Dystrophy type 1 multisystem involvement leads to functional impairment
      with an increased risk of falling. This multinational study estimates the
      prevalence of falls and fall-associated fractures. A web-based survey among
      disease-specific registries (Germany, UK and The Netherlands) was carried out
      among DM1 ambulant adults with a total of 573 responses retrieved. Results
      provided a risk ratio estimation of 30%-72% for falls and of 11%-17% for
      associated fractures. There was no significant difference for falls between male
      and female, but there was for fall-related fractures with a higher prevalence in
      women. Balance and leg weakness were the most commonly reported causes for
      falling. This study is based on a voluntary retrospective survey with naturally
      inherent limitations; however, the sample size allows for robust comparisons. The
      estimated risk of falls in this cohort with a mean age of 46 years compares to a
      previous estimation for a healthy population of over 65 years of age. These
      results suggest a premature-ageing DM1 phenotype with an increased risk of
      falling depending on age and disease severity that, so far, might have been
      underestimated. This may have clinical implications for the development of care
      guidelines and when testing new interventions in this population.

PMID- 29361395
TI  - Hereditary myopathy with early respiratory failure (HMERF): Still rare, but
      common enough.
AB  - Phenotypic and genetic/allelic heterogeneity is a feature of many neuromuscular
      disorders, titinopathies being one of them. Hereditary Myopathy with Early
      Respiratory Failure (HMERF) has been considered an extremely rare disease with
      definite clinicopathologic hallmarks, and geographically restricted to the
      Northern European population with one single titin gene defect identified in
      previous years. The recent availability of massive parallel sequencing
      techniques, allowing the screening of all coding regions of the genome in
      undiagnosed patients, together with a growing awareness of the main muscle MRI
      features of the disease, has led to the discovery of a number of HMERF families
      and new titin mutations in the last five years. We reviewed the clinical,
      pathological and muscle imaging findings that are still cornerstones for the
      diagnosis of this disease, as well as the most recent molecular genetic findings.
      HMERF is more common and geographically widespread than previously expected, and
      the knowledge of the whole phenotypic and molecular spectrum of HMERF can
      increase the number of diagnosed patients considerably.

PMID- 29361396
TI  - Childhood-onset form of myotonic dystrophy type 1 and autism spectrum disorder:
      Is there comorbidity?
AB  - Myotonic dystrophy type 1 (DM1) is a multisystemic disorder with neuromuscular
      symptoms and brain dysfunctions. Depending on the phenotypic expression, the
      degree of cognitive impairment remains heterogeneous, ranging from moderate to
      severe intellectual disability in the congenital form, to executive, visuospatial
      and personality dysfunction in the adult-onset form. Studies exploring the
      cognitive or psychiatric impairments in the childhood form of DM1, characterized
      by an age of onset between one and ten years, uneventful pre and post natal
      history and normal development the first year of life, are scarce and show
      conflicting results in regard to a comorbid diagnosis of Autism Spectrum Disorder
      (ASD). The aim of the current review is to summarize diagnostic criteria and
      update the state of the debate regarding comorbidity. Evidence from 9 studies
      collected in PubMed database (representing a total of 175 cases) focusing on
      clinical, neuropsychological and neuroimaging domains in childhood DM1 is
      considered and similarities or differences between childhood DM1 and ASD are
      identified. Highlighting what is known about the neurocognitive features specific
      to the childhood-onset form of DM1 could help (1) propose early screening
      regarding socio-emotional and attentional/executive functions or (2) implement
      therapeutic programs based on reinforcement of executive skills or social
      cognition.

PMID- 29361397
TI  - 227th ENMC International Workshop:: Finalizing a plan to guarantee quality in
      translational research for neuromuscular diseases Heemskerk, Netherlands, 10-11
      February 2017.

PMID- 29361398
TI  - Platform for systems medicine research and diagnostic applications in psychotic
      disorders-The METSY project.
AB  - Psychotic disorders are associated with metabolic abnormalities including
      alterations in glucose and lipid metabolism. A major challenge in the treatment
      of psychosis is to identify patients with vulnerable metabolic profiles who may
      be at risk of developing cardiometabolic co-morbidities. It is established that
      both central and peripheral metabolic organs use lipids to control energy balance
      and regulate peripheral insulin sensitivity. The endocannabinoid system,
      implicated in the regulation of glucose and lipid metabolism, has been shown to
      be dysregulated in psychosis. It is currently unclear how these endocannabinoid
      abnormalities relate to metabolic changes in psychosis. Here we review recent
      research in the field of metabolic co-morbidities in psychotic disorders as well
      as the methods to study them and potential links to the endocannabinoid system.
      We also describe the bioinformatics platforms developed in the EU project METSY
      for the investigations of the biological etiology in patients at risk of
      psychosis and in first episode psychosis patients. The METSY project was
      established with the aim to identify and evaluate multi-modal peripheral and
      neuroimaging markers that may be able to predict the onset and prognosis of
      psychiatric and metabolic symptoms in patients at risk of developing psychosis
      and first episode psychosis patients. Given the intrinsic complexity and
      widespread role of lipid metabolism, a systems biology approach which combines
      molecular, structural and functional neuroimaging methods with detailed metabolic
      characterisation and multi-variate network analysis is essential in order to
      identify how lipid dysregulation may contribute to psychotic disorders. A
      decision support system, integrating clinical, neuropsychological and
      neuroimaging data, was also developed in order to aid clinical decision making in
      psychosis. Knowledge of common and specific mechanisms may aid the etiopathogenic
      understanding of psychotic and metabolic disorders, facilitate early disease
      detection, aid treatment selection and elucidate new targets for pharmacological
      treatments.

PMID- 29361399
TI  - Current trends in diagnosis and treatment of mental disorders.

PMID- 29361400
TI  - Future coordination and integration of the results of the EU funded projects on
      schizophrenia and other mental disorders.

PMID- 29361401
TI  - Immobilization and image-guidance methods for radiation therapy of limb extremity
      soft tissue sarcomas: Results of a multi-institutional survey.
AB  - Radiation therapy for limb-extremity soft tissue sarcoma (STS) requires accurate,
      reproducible dose delivery. However, patient positioning is challenging and there
      is a lack of existing guidelines to assist institutional standardization.
      Therefore, we conducted a multi-institutional international survey of STS
      immobilization, image guidance methods, and treatment protocols to investigate
      current practice. Seventy-three UK radiotherapy centers and 15 hospitals in 7
      other countries completed a questionnaire on STS immobilization and image
      guidance procedures. Specifically, the survey collated information on the current
      usage of immobilization equipment, including custom devices, patient setup
      tolerances, the use of written protocols, the modality and frequency of image
      guidance, the method of treatment, allocated treatment times, and the application
      of surgical clips. Multiple combinations of immobilization devices were reported.
      In the UK, 12%, 40%, 30%, 12%, and 5% use 1, 2, 3, 4, and 5 types of device for
      lower limb STS. Vacuum bag plus either foot or ankle support was most common
      (66%). Of 15 international centers, 27%, 60%, 7%, 0%, 7% use 1, 2, 3, 4, 5
      devices, with vacuum bags (73%) and thermoplastic (47%) predominant, similar to
      UK values of 77% and 52%. For image guidance, in the UK, 37% use kV planar, 34%
      use MV planar, and 16% use cone-beam CT for the first 3 fractions and then
      weekly. Internationally, daily imaging was more prevalent with 33% using kV
      planar, 7% MV planar, and 40% cone-beam CT daily. Custom devices plus
      combinations of devices, along with 5- and 10-mm set-up tolerances, were most
      commonly reported. Less than half of centers have written treatment protocols.
      Conventional treatment is most common in the UK, with only 42% using conformal
      techniques. Treatment is allocated between 10 and 30 minutes. Twenty-six percent
      of UK centers and 53% of international centers use surgical clips. Across
      treatment centers, there is no consistent approach to STS immobilization, image
      guidance methods, or treatment protocols assessed by this survey. A wide variety
      of immobilization devices and configurations are utilized, and the frequency and
      modality of imaging are similarly diverse. In the absence of guidelines, the
      creation of an online repository of example immobilization techniques could
      enable centers to compare a diversity of cases. The availability of a forum for
      viewing and discussing a range of cases could potentially lead to improved
      patient setup and reduce the time taken to devise an individual immobilization
      strategy.

PMID- 29361402
TI  - Does urinary tract infection alter fetal fibronectin vaginal swab results?

PMID- 29361403
TI  - Structure based virtual screening of the Ebola virus trimeric glycoprotein using
      consensus scoring.
AB  - Ebola virus (EBOV) causes zoonotic viral infection with a potential risk of
      global spread and a highly fatal effect on humans. Till date, no drug has gotten
      market approval for the treatment of Ebola virus disease (EVD), and this perhaps
      allows the use of both experimental and computational approaches in the antiviral
      drug discovery process. The main target of potential vaccines that are recently
      undergoing clinical trials is trimeric glycoprotein (GP) of the EBOV and its
      exact crystal structure was used in this structure based virtual screening study,
      with the aid of consensus scoring to select three possible hit compounds from
      about 36 million compounds in MCULE's database. Amongst these three compounds,
      (5R)-5-[[5-(4-chlorophenyl)-1,2,4-oxadiazol-3-yl]methyl]-N-[(4
      methoxyphenyl)methyl]-4,5-dihydroisoxazole-3-carboxamide (SC-2, C21H19ClN4O4)
      showed good features with respect to drug likeness, ligand efficiency metrics,
      solubility, absorption and distribution properties and non-carcinogenicity to
      emerge as the most promising compound that can be optimized to lead compound
      against the GP EBOV. The binding mode showed that SC-2 is well embedded within
      the trimeric chains of the GP EBOV with molecular interactions with some amino
      acids. The SC-2 hit compound, upon its optimization to lead, might be a good
      potential candidate with efficacy against the EBOV pathogen and subsequently
      receive necessary approval to be used as antiviral drug for the treatment of EVD.

PMID- 29361404
TI  - Using YouTube analytics to evaluate a Chinese video-based lecture regarding
      Parkinson's disease.

PMID- 29361405
TI  - Neuroinflammation and sympathetic overactivity: Mechanisms and implications in
      hypertension.
AB  - Essential hypertension is a multifactorial disorder with a strong genetic
      predisposition. Although anti-hypertensive medications have drastically reduced
      cardiovascular diseases mortality and morbidity rates, a significant percentage
      of hypertensive individuals currently on anti-hypertensive therapy, remain
      hypertensive. In spite of the emergence of transgenic animals and sophisticated
      tools to study the pathophysiology of hypertension, unraveling the causal
      mechanisms remains a challenge. Research on borderline hypertensive humans and/or
      prehypertensive rat models revealed an elevation in centrally-mediated
      sympathetic activity and a heightened neuroinflammatory state. Hyperactive brain
      renin angiotensin system (RAS), oxidative stress and neuroinflammation in
      brainstem cardiovascular centers and other brain regions are implicated as key
      factors in augmenting sympathetic activity in hypertension and other
      cardiovascular abnormalities. Angiotensin (Ang) II, the main RAS effector
      peptide, has been shown to trigger significant upsurges in pro-inflammatory
      cytokines and reactive oxygen species (ROS). Both microglial and astroglial
      cells, via a host of different mechanisms, contribute to pro-inflammatory states
      and ROS generation in the brain. Hence, it becomes essential to understand the
      impact of Ang II and neuroinflammatory mediators on the impairment of
      cardioregulatory centers in the brain, and to investigate the role of glia in Ang
      II-mediated sympathoexcitation. Understanding the mechanisms leading to an
      elevation in neuroinflammatory states, and the possible ways of counteracting it,
      could aid in devising better therapeutic strategies for the treatment of
      cardiovascular diseases and hypertension. This review primarily focuses on the
      molecular aspects of hypertension from a neuroinflammatory standpoint within
      brainstem cardiovascular centers.

PMID- 29361406
TI  - Politics is Now a Major Risk Factor for Illness and Death in America.

PMID- 29361407
TI  - Kinematic measures for upper limb robot-assisted therapy following stroke and
      correlations with clinical outcome measures: A review.
AB  - AIM OF THE STUDY: This review classifies the kinematic measures used to evaluate
      post-stroke motor impairment following upper limb robot-assisted rehabilitation
      and investigates their correlations with clinical outcome measures. METHODS: An
      online literature search was carried out in PubMed, MEDLINE, Scopus and IEEE
      Xplore databases. Kinematic parameters mentioned in the studies included were
      categorized into the International Classification of Functioning, Disability and
      Health (ICF) domains. The correlations between these parameters and the clinical
      scales were summarized. RESULTS: Forty-nine kinematic parameters were identified
      from 67 articles involving 1750 patients. The most frequently used parameters
      were: movement speed, movement accuracy, peak speed, number of speed peaks, and
      movement distance and duration. According to the ICF domains, 44 kinematic
      parameters were categorized into Body Functions and Structure, 5 into Activities
      and no parameters were categorized into Participation and Personal and
      Environmental Factors. Thirteen articles investigated the correlations between
      kinematic parameters and clinical outcome measures. Some kinematic measures
      showed a significant correlation coefficient with clinical scores, but most were
      weak or moderate. CONCLUSIONS: The proposed classification of kinematic measures
      into ICF domains and their correlations with clinical scales could contribute to
      identifying the most relevant ones for an integrated assessment of upper limb
      robot-assisted rehabilitation treatments following stroke. Increasing the
      assessment frequency by means of kinematic parameters could optimize clinical
      assessment procedures and enhance the effectiveness of rehabilitation treatments.

PMID- 29361408
TI  - Supplementing in vitro embryo production media by NPPC and sildenafil affect the
      cytoplasmic lipid content and gene expression of bovine cumulus-oocyte complexes
      and embryos.
AB  - In our study, we added natriuretic peptide type C (NPPC) and/or sildenafil during
      in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs) followed by
      in vitro culture (IVC) of embryos with or without sildenafil. We evaluated the
      effects on the lipid content (LC) of oocytes and embryos and also verified the
      expression of 96 transcripts related to competence in matured COCs and 96
      transcripts related to embryo quality in blastocysts. After IVM, LC was decreased
      in oocytes by NPPC while sildenafil did not affect LC in oocytes. The genes
      involved in lipid metabolism and lipid accumulation (DGAT1, PLIN2and PLIN3) were
      not affected in COCs after treatment during IVM, although the expression of PTX3
      (a cumulus cells expansion biomarker) was increased and the hatched blastocyst
      rate was increased by NPPC during IVM. During IVM, sildenafil increased the mRNA
      relative abundance of HSF1 and PAF1 and decreased REST in blastocysts. The use of
      sildenafil in IVC increased the LC of blastocysts. The mRNA abundance in
      blastocysts produced during IVC with sildenafil was changed for ATF4, XBP1,
      DNMT3A, DNMT3B, COX2, and SOX2. Although NPPC reduced the LC of oocytes after IVM
      and upregulated markers for cumulus expansion, embryo production was not affected
      and the produced blastocysts were able to regain their LC after IVC. Finally, the
      use of sildenafil during IVC increased the cytoplasmic LC of embryos but did not
      affect embryo quality, as measured by analysis of 96 transcripts related to
      embryo quality.

PMID- 29361409
TI  - [M. Le Guen, M. Carbonnel et JM Ayoubi reply to the correspondence by C.
      Lallemenad et MP Debord on the article by A. Rousseau et al.: "Comparative study
      about enhanced recovery after cesarean section: what benefits, what risks?"
      Gynecol Obstet Fertil Senol 2017;45:287-92].

PMID- 29361410
TI  - [Presentation and outcome of breast cancer under 40 years - A French monocentric
      study].
AB  - OBJECTIVE: The aim of our study was to evaluate the impact of young age on breast
      cancer presentation and women's prognosis. METHODS: We performed a descriptive
      retrospective study in the university teaching hospital of Tours from January
      2007 to December 2013. All women managed for an invasive breast cancer were
      included. The population was divided in 2 groups according to age: <=40 years
      and>40 years. We studied differences in histological, management and outcome
      characteristics. RESULTS: Two thousand and eighty three women with an invasive
      breast cancer were included. A hundred and fifty five in the group of women with
      an age <=40 years and 1928 in the group of women with an age>40 years.
      Histological characteristics of breast cancer in younger women were worse than in
      their older counterparts (with more aggressive features: grade 3, negative
      hormone receptors, positive Her 2 status, triple negative molecular sub-type).
      Overall survival was lower in young women than in women age>40 years (P=0.05),as
      was recurrence free survival (P<0.001), locoregional recurrence free survival
      (P=0.02) and distant metastasis free survival(P<0.001). Age<=40 years was an
      independent factor predictive of poor recurrence free survival. CONCLUSION: In
      our study we found an impact of age<=40 years on invasive breast cancer
      presentation and prognosis.

PMID- 29361411
TI  - Unplanned emergency department or urgent care visits after outpatient rotator
      cuff repair: potential for avoidance.
AB  - BACKGROUND: With the cost of health care rising, the potential to avoid costs
      from an unplanned return to the emergency department (ED) or urgent care center
      (UC) after elective outpatient rotator cuff repair (RCR) has been discussed but
      not extensively assessed. METHODS: Outpatient RCR procedures were queried in a
      closed health care system, and all unplanned ED and UC visits within 7 days of
      procedures were collected and compared with other typical outpatient orthopedic
      procedures (knee arthroscopy, carpal tunnel release, and anterior cruciate
      ligament reconstruction). Avoidable diagnoses (ADs) for the unplanned visits were
      defined in advance as visits for (1) constipation, (2) nausea or vomiting, (3)
      pain, and (4) urinary retention. Final tallies of all visits versus visits with
      ADs were compared. RESULTS: From June 2015 to May 2016, 1306 outpatient RCRs were
      performed (729 male and 577 female patients; average age, 60 years). Of the
      patients, 90 returned for ED or UC visits (6.9%), with 34 for ADs (2.6%). Pain
      was the most common AD. However, when RCR was compared with other case types, ED
      or UC visits for urinary retention were significantly more common (P = .007),
      whereas there was no significant difference with the other ADs. The 1306 RCRs led
      to a greater proportion of ED or UC visits than the combined 5825 other cases
      studied (P < .001). DISCUSSION AND CONCLUSIONS: Unplanned ED visits within 7 days
      of outpatient RCR are measurable and in many cases, such as ED or UC visits for
      pain, are avoidable. Visits for urinary retention are seen more commonly after
      RCR. Outpatient RCR led to more unplanned ED and UC visits than other common
      outpatient orthopedic surgical procedures.

PMID- 29361412
TI  - Prevalence of Propionibacterium acnes in the glenohumeral compared with the
      subacromial space in primary shoulder arthroscopies.
AB  - HYPOTHESIS: We hypothesized that the prevalence of Propionibacterium acnes in
      patients undergoing primary shoulder arthroscopy is equal in the glenohumeral
      space compared with the subacromial space. METHODS: Patients aged 18 years or
      older with shoulder arthroscopies were included. The exclusion criteria were
      prior shoulder operations, complete rotator cuff tears, systemic inflammatory
      diseases, tumors, shoulder injections within 6 months of surgery, and antibiotic
      therapy within 14 days preoperatively. After standardized skin disinfection with
      Kodan Tinktur Forte Gefarbt, a skin swab was taken at the posterior portal.
      Arthroscopy was performed without cannulas, prospectively randomized to start
      either in the glenohumeral space or in the subacromial space, with direct
      harvesting of a soft-tissue biopsy specimen. Sample cultivation was conducted
      according to standardized criteria for bone and joint aspirate samples and
      incubated for 14 days. Matrix-assisted laser desorption-ionization time-of-flight
      spectrometry was used for specimen identification in positive culture results.
      RESULTS: The study prospectively included 115 consecutive patients with normal C
      reactive protein levels prior to surgery (54.8% men; mean age, 47.2 +/- 14.6
      years). P acnes was detected on the skin after disinfection in 36.5% of patients,
      in the glenohumeral space in 18.9%, and in the subacromial space in 3.5% (P =
      .016). CONCLUSION: The prevalence of P acnes is significantly higher in the
      glenohumeral space compared with the subacromial space in primary shoulder
      arthroscopies. The results do not confirm the contamination theory but also
      cannot clarify whether P acnes is a commensal or enters the joint hematologically
      or even lymphatically or via an unknown pathway. Despite standardized surgical
      skin disinfection, P acnes can be detected in skin swab samples in more than one
      third of patients.

PMID- 29361413
TI  - Os acromiale open reduction and internal fixation: a review of iliac crest
      autogenous bone grafting and local bone grafting.
AB  - BACKGROUND: Symptomatic os acromiale are fairly uncommon, and treatment has
      included fragment excision, decompression, and open reduction and internal
      fixation. Nonunion rates as high as 40% have been reported after fixation of os
      acromiale. This study assessed whether union of an os acromiale could be reliably
      achieved without the use of an iliac crest bone graft. METHODS: This was a
      retrospective study of 32 consecutive shoulders that were treated with screw
      fixation and a local bone graft or iliac crest bone graft. The mean age was 50.3
      years (range, 21-74 years), and the mean follow-up was 46.9 months (range, 12-120
      months). Fusion was assessed clinically and radiologically. RESULTS: All 32 os
      acromiale were fused by 3 months on x-ray imaging. There were 18 shoulders in the
      iliac crest bone graft group and 14 in the local bone graft group. Rotator cuff
      repairs were performed concomitantly in 25 patients. Hardware was removed in 4
      patients, a seroma was drained in 1 patient, and a superficial infection occurred
      in 1 patient. CONCLUSION: This is the largest study of os acromiale fixation
      using screws and a tension band to our knowledge. We report a 100% union rate
      using this technique, with 13% requiring hardware removal and the occurrence of 1
      superficial infection. This study shows a local bone graft is as effective as
      iliac crest bone graft in achieving fusion.

PMID- 29361414
TI  - The evaluation of safety and efficacy of colistin use in pediatric intensive care
      unit: Results from two reference hospitals and review of literature.
AB  - Colistin, an old cationic polypeptide antibiotic, have been reused due to rising
      incidence of infections caused by multi-drug resistant (MDR) Gram-negative
      microorganisms and the lack of new antibiotics. Therefore, we evaluated safety
      and efficacy of colistin in treatment of these infections. This study included
      104 critically ill children with a median age of 55,9 months between January 2011
      and January 2016. Nephrotoxicity occurred in 11 (10.5%) patients. Nephrotoxicity
      occurred between the third and seventh day of treatment in 63% of colistin
      induced nephrotoxicity episodes. The subgroup analysis between the patients who
      developed nephrotoxicity during colistin treatment and those that did not, showed
      no significant difference in terms of age, underlying disease, cause for PICU
      admission and type of infection required colistin treatment, P values were 0.615,
      0.762, 0.621, 0.803, respectively. All patients were receiving a concomitant
      nephrotoxic agent (P = 0,355). The majority of the patients (52%) were having
      primary or secondary immune deficiency in treatment failure group and the most
      common cause of PICU admission was sepsis in treatment failure group, P values
      were 0.007 and 0.045, respectively. Mortality attributed to colistin failure and
      crude mortality were 14.4% and 29.8%, respectively. In conclusion, colistin may
      have a role in the treatment of infections caused by multidrug-resistant Gram
      negative bacteria in critically ill children. However, the patients have to be
      followed for side effects throughout colistin treatment, not for only early
      stage. And the clinicians should be aware of increase in the rate of
      nephrotoxicity in patients those have been receiving a concomitant nephrotoxic
      agent.

PMID- 29361415
TI  - The association between erythromycin monotherapy for Mycobacterium avium complex
      lung disease and cross-resistance to clarithromycin: A retrospective case-series
      study.
AB  - Long-term, low-dose erythromycin monotherapy, based on the anti-inflammatory
      effects of macrolides, has been reported to have the potential to suppress the
      exacerbation of Mycobacterium avium complex (MAC) lung disease with less
      toxicity. It remains unclear whether erythromycin monotherapy induces cross
      resistance to clarithromycin, a key drug for MAC. To clarify this point, we
      conducted a retrospective, single-center, case-series study on patients with MAC
      lung disease who underwent erythromycin monotherapy for at least 6 months. Drug
      susceptibility tests, before and after erythromycin treatment initiation, were
      analyzed. Thirty-three patients were included in our study. All 33 patients
      showed susceptibility to clarithromycin for MAC both before and after
      erythromycin monotherapy. There was no significant difference in clarithromycin
      minimum inhibitory concentrations between before and after erythromycin treatment
      (median difference = 0 MUg/ml; P = .313, Wilcoxon's signed-rank test). We
      conclude that erythromycin monotherapy for MAC lung disease may not induce cross
      resistance to clarithromycin.

PMID- 29361417
TI  - A Review of Resources and Methodologies Available for Teaching and Assessing
      Patient-Related Communication Skills in Radiology.
AB  - ACGME expectations for radiology trainees' proficiencies in communication skills
      pose a challenge to program directors who wish to develop curricula addressing
      these competencies. Numerous educational resources and pedagogical approaches
      have emerged to address such competencies specifically for radiology, but have
      yet to be systematically catalogued. In this paper, we review and compile these
      resources into a toolkit that will help residencies develop curricula around
      patient-centered communication. We describe numerous web-based resources and
      published models that have incorporated innovative, contemporary pedagogical
      techniques. In undertaking this compilation, our hope is to kindle discussion
      about the development of formalized or standardized communication curricula or
      guides for radiology residencies.

PMID- 29361416
TI  - Laboratory surveillance of antimicrobial resistance and multidrug resistance
      among Streptococcus pneumoniae isolated in the Kinki region of Japan, 2001-2015.
AB  - The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced among children
      in Japan in 2010. There are no long-term multicenter surveillance studies of
      antimicrobial resistance in S. pneumoniae before and after the introduction of
      PCV7. Therefore, we examined chronological trends in antimicrobial resistance
      among 4534 strains of S. pneumoniae isolated from both children and adults in the
      Kinki region of Japan during 2001-2015. High-level penicillin and third
      generation cephalosporin resistance in S. pneumoniae increased among both
      children and adults during the period before the introduction of PCV7 (2001
      2010). Besides penicillin and cephalosporin, pneumococcal carbapenem and
      macrolide resistance increased among children. The rate of resistance to these
      antibiotics was higher among children than among adults. The introduction of PCV7
      decreased the rate of non-susceptibility to beta-lactam antibiotics and the rate
      of multidrug resistant S. pneumoniae among children, but not among adults.

PMID- 29361418
TI  - Target engagement and histopathology of neuraxial resiniferatoxin in dog.
AB  - OBJECTIVE: To evaluate target engagement of intracisternally (IC) delivered TRPV1
      agonist, resiniferatoxin (RTX), as measured by primary afferent and dorsal horn
      substance P immunoreactivity (sP-IR), histopathology and thermal escape latencies
      in dogs. STUDY DESIGN: Prospective experimental trial. ANIMALS: Fourteen adult
      male Beagle dogs, weighing 10.3-13.2 kg; 11 dogs surviving to scheduled
      euthanasia. METHODS: Anesthetized dogs were randomly assigned to be administered
      IC RTX (3.6 MUg, 0.1 mL kg-1) in a hyperbaric (hRTX, n = 6), normobaric (nRTX, n
      = 4) vehicle or a hyperbaric vehicle (hVehicle, n = 4). Over 16 days, animals
      were examined for thoracic and pelvic limb paw thermal withdrawal latencies and
      neurologic function. Spinal cords, trigeminal ganglia and dorsal root ganglia
      (DRGs) were assessed for morphologic changes and sP-IR. RESULTS: IC RTX in
      anesthetized dogs resulted in a < 1 hour increase in blood pressure. Acute
      reactions leading to euthanasia within 8 hours occurred in three dogs (two hRTX,
      one nRTX). All other animals recovered with normal neurologic, bowel and bladder
      function. Final groups were: vehicle n = 4, hRTX n = 4 and nRTX n = 3. Animals in
      nRTX and hRTX showed increases in escape latencies in thoracic paws and, to a
      lesser extent, in pelvic paws, correlating to a loss of sP-IR in cervical cord
      with smaller reductions in thoracic and lumbar cord. In animals surviving to
      euthanasia, thickening of the arachnoid membrane (predominantly in the cervical
      region) was the most consistent change. This change, present in controls, was
      interpreted to be vehicle related. There was no evidence of structural changes in
      brain and spinal cord. CONCLUSIONS AND CLINICAL RELEVANCE: IC RTX produced
      localized loss of spinal and DRG sP with a corresponding thermal analgesia,
      absent motor impairment or spinal pathology. Loss of three animals emphasizes the
      need to refine the use of this promising therapeutic modality in managing
      companion animal pain.

PMID- 29361419
TI  - Effects of mismatches distant from the target position on gene correction with a
      5'-tailed duplex.
AB  - The introduction of a 5'-tailed duplex (5'-TD) fragment into cells corrects a
      base-substitution mutation in a target DNA. We previously reported that the gene
      correction efficiency was improved when a frameshift type of second mismatch was
      present ~330 bases distant from the target position, between the target DNA and
      the 5'-TD fragment. In this study, the effects of the second mismatches on the
      gene correction were further examined. Base-base mismatches 332 bases distant
      from the target position slightly enhanced gene correction, but less efficiently
      than the previously studied frameshift mismatches. The gene correction efficiency
      was also increased when the distance between the target position and the second
      frameshift mismatch was changed to ~270 bases. These results suggested that the
      introduction of an appropriate second frameshift mismatch into the 5'-TD fragment
      improves the gene correction efficiency.

PMID- 29361420
TI  - Quantification of burnout in emergency nurses: A systematic review and meta
      analysis.
AB  - BACKGROUND: Previous studies showed increased levels of absenteeism, drug abuse,
      depression, and symptoms allied with burnout in emergency nurses. This meta
      analysis aimed to quantify the three dimensions of burnout in emergency nurses
      and estimate the proportion of nurses who experience higher than tolerable levels
      of burnout. MATERIALS AND METHODS: A systematic search was conducted on PubMed,
      Scielo, Xueshu Baidu and Informa databases with a cut-off time between 1997 and
      2017 to retrieve published papers in any language that had estimated the burnout
      levels in emergency nurses by using MBI scale. RESULTS: We identified a total of
      11 eligible studies. The total mean estimate was moderate for emotional
      exhaustion (25.552), but clearly trending towards higher level, whereas
      depersonalization (10.383) and lack of personal accomplishment (30.652) showed
      higher burnouts levels. The proportion of emergency nurses suffering from high
      emotional exhaustion, high depersonalization, and low personal accomplishment was
      40.5%, 44.3%, and 42.7%, respectively. CONCLUSION: Burnout is detrimental to
      achieving high-quality healthcare services and causes a loss of productivity. It
      is high time for nursing leader and management personnel to identify appropriate
      measures to counteract burnout.

PMID- 29361421
TI  - A Systematic Review of Arthroscopic Versus Open Tenotomy of Iliopsoas Tendonitis
      After Total Hip Replacement.
AB  - PURPOSE: To conduct a systematic review of the literature comparing patient
      outcomes following arthroscopic and open operative management of iliopsoas
      tendonitis (IPT) following total hip replacement (THR). METHODS: This review
      study was conducted in accordance with the Preferred Reporting Items for
      Systematic review and Meta-Analysis (PRISMA) statement. Inclusion criteria were
      as follows: outcome studies following open or arthroscopic iliopsoas tendon
      release after THR with at least 6 months of follow-up, English language, and
      human studies. The exclusion criteria included case reports, articles evaluating
      nonsurgical management or cup revision, and articles without a specific diagnosis
      of IPT or in which results between open and arthroscopic treatment were reported
      in conjunction. RESULTS: A total of 131 studies were initially retrieved, with 7
      satisfying all inclusion criteria (4 studies on arthroscopic tenotomy and 3
      studies on open tenotomy). The review included a total of 88 patients with IPT-61
      patients treated arthroscopically and 27 patients treated with open tenotomy. In
      total, 77 of the 88 patients demonstrated successful outcomes following surgery.
      In the group treated with arthroscopy, 91.8% (56/61) of patients had successful
      outcomes, whereas in those treated with open tenotomy, 77.8% (21/27) of patients
      had successful outcomes. Of patients with signs of mechanical impingement from
      acetabular component overhang, those who underwent open tenotomy had complete
      pain relief in 6/8 patients (75%) compared to arthroscopic tenotomy in which
      there was relief in 40/43 patients (93%). CONCLUSIONS: Arthroscopic iliopsoas
      release for management of IPT is suggested to be an effective minimally invasive
      operative technique that may also yield a lower complication rate in comparison
      to open tenotomy. Tenotomy, both arthroscopic and open, are successful treatment
      options for IPT, including those with signs of mechanical impingement, and are
      recommended prior to cup revision. LEVEL OF EVIDENCE: Level IV, systematic review
      of level IV studies.

PMID- 29361422
TI  - Arthroscopically-Assisted Latissimus Dorsi Transfer for Irreparable Rotator Cuff
      Insufficiency: Modes of Failure and Clinical Correlation.
AB  - PURPOSE: The main objective of this retrospective study was to analyze the rate
      and modes of failure of latissimus dorsi transfer (LDT). The secondary objective
      was to evaluate whether a rupture of the transfer was associated with a worse
      outcome. METHODS: During a 2-year period, we performed consecutive LDTs either
      for irreparable posterior-superior rotator cuff tears (RCTs) or for failed prior
      repair. All the LDTs were performed by a single surgeon. All transfers were
      arthroscopically assisted and fixed as a tubularized LD tendon in a bone tunnel
      inside the humeral head. Three metal clips were placed systematically
      intraoperatively in the tubularized tendon at a fixed distance of 2, 4, and 6 cm
      from the tip of the tendon. Immediate postoperative standard anteroposterior
      radiographs were performed and the position of the metal clips was compared with
      their position on radiographs performed at 6 weeks and 3 and 24 months
      postoperatively. Constant, Subjective Shoulder Value (SSV), Simple Shoulder Test
      (SST), Activities of daily living requiring active external rotation (ADLER),
      visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) scores and
      patient's subjective satisfaction (assessed by self-questionnaire) at last follow
      up were compared between patients who had a rupture of the transfer and those who
      did not. RESULTS: Sixty-six patients were included. Six of 66 patients (9%) were
      lost to follow-up. There were 11 complications (18.3%) in the global series (10
      hematoma and 1 subscapularis retear). At a mean 35.2 months (range 24-50 months),
      there were 23/60 cases of rupture (38%). The 7 scores and the satisfaction
      reported were significantly lower for patients who had a rupture of the transfer
      versus those who had an intact transfer: Constant score, 42.8 versus 68.7 (P =
      .001); SSV, 48.9 versus 71.6 (P = .001); SST, 4.8 versus 8.4 (P = .012); ADLER,
      19.7 versus 26.7 (P = .005); VAS, 3.7 versus 2.3 (P = .082); ASES, 55.4 versus
      74.8 (P = .056); and 13% of either satisfied or very satisfied patients versus
      78% (P < .001). CONCLUSIONS: The rate of rupture of LDT is high (38%). With
      complete healing of LDT, the outcome is significantly lower in those with rupture
      compared with those without rupture, showing that LDT can efficiently treat
      massive and irreparable RCT. LEVEL OF EVIDENCE: Level IV, case series treatment
      study.

PMID- 29361423
TI  - Distal Mononeuropathy Before and After Arthroscopic Rotator Cuff Repair: A
      Prospective Investigation.
AB  - PURPOSE: The purpose of this study was to characterize the occurrence of distal
      mononeuropathy (DMN) in patients before and after arthroscopic rotator cuff
      repair (RCR) as well as resolution of the symptoms. METHODS: One hundred one
      patients over the age of 18 undergoing arthroscopic RCR +/- concurrent procedures
      completed a questionnaire regarding the presence of a symptomatic DMN. Patients
      with history of diabetic neuropathy, cervical radiculopathy, brachial plexopathy,
      or Spurling sign were excluded. All patients underwent physical examination to
      determine the characteristics and location of symptoms. Postoperatively, patients
      underwent repeat examination at 2, 6, and 12 weeks. RESULTS: Preoperatively, 19%
      (19/101) of RCR patients described DMN symptoms (9 median nerve symptoms, 5 ulnar
      nerve symptoms, 4 nonspecific symptoms, one with both ulnar and median nerve
      symptoms). Ninety percent (17/19) patients with preoperative DMN symptoms
      described resolution within the final 12 weeks of follow-up. A portion of
      previously asymptomatic RCR patients (12/82) developed new DMN symptoms (6
      nonspecific symptoms, 3 ulnar nerve symptoms, 2 median nerve symptoms, one radial
      sensory nerve symptoms) postoperatively, with 92% (11/12) having resolution by
      the final 12-week follow-up. At the final 12 weeks, 3 RCR patients had DMN
      symptoms with 2 of those 3 patients having their symptoms existing
      preoperatively. CONCLUSIONS: This study supports the hypothesis that DMN can be a
      preexisting finding in patients undergoing arthroscopic RCR. Similarly, it is
      common for patients undergoing arthroscopic RCR to develop new DMN symptoms
      following their procedure. Regardless, there is good evidence to show that a
      large majority of both groups of patients will go on to have resolution of their
      symptoms. LEVEL OF EVIDENCE: Level IV, prospective case series.

PMID- 29361424
TI  - Effect of Aromatase Inhibitor Therapy on Sleep and Activity Patterns in Early
      stage Breast Cancer.
AB  - INTRODUCTION: Adherence to aromatase inhibitor (AI) therapy is poor, often
      because of treatment-emergent side effects, including musculoskeletal symptoms,
      fatigue, and insomnia. In the present analysis, we examined the sleep patterns
      and daytime function both objectively using actigraphy and subjectively using
      validated questionnaires in women initiating AI therapy. PATIENTS AND METHODS:
      Postmenopausal women with stage 0-III hormone receptor-positive breast cancer who
      were initiating AI therapy were eligible. The patients wore actigraphy devices
      for 10 consecutive days and completed questionnaires at baseline before the
      initiation of AI and after 3 months of AI therapy. Associations between the
      baseline demographics and symptoms, changes in patient-reported outcomes and
      actigraphy measures from baseline to 3 months of AI therapy and discontinuation
      of AI therapy were examined using sign tests, logistic regression models,
      Spearman's correlation, and linear mixed models. RESULTS: Forty-two patients
      (86%) completed the baseline assessments and 23 patients (47%) completed both the
      baseline and the 3-month assessments. Objectively measured daytime function as
      measured by total daytime activity decreased during the 3 months after starting
      AI (232,566 activity count vs. 204,205 activity count; P = .023), and the
      decrease was more evident in women with higher baseline physical function.
      Reduced daytime activity correlated with increased fatigue (rho = -0.49; P =
      .017). CONCLUSION: Daytime function decreased after initiation of AI therapy and
      correlated moderately with increased fatigue, although no association was
      identified with changes in pain or sleep quality. Additional studies are required
      to understand why function is reduced, which could have implications for
      interventions to improve patient tolerance of, and persistence with, AI therapy.

PMID- 29361425
TI  - The Clinical Presentation, Survival Outcomes, and Management of Patients With
      Renal Cell Carcinoma and Cardiac Metastasis Without Inferior Vena Cava
      Involvement: Results From a Pooled Clinical Trial Database and Systematic Review
      of Reported Cases.
AB  - BACKGROUND: Cardiac metastases from renal cell carcinoma (RCC) are uncommon and
      there are limited data regarding the presentation and outcomes of this
      population. The objective of this study was to evaluate the characteristics and
      outcomes of patients with RCC with cardiac metastasis without inferior vena cava
      (IVC) involvement. MATERIALS AND METHODS: We conducted a pooled retrospective
      analysis of metastatic RCC patients treated in 4 clinical trials. Additionally,
      we conducted a systematic review of cases reported in the literature from 1973 to
      2015. Patients with cardiac metastases from RCC without IVC involvement were
      included. Patient and disease characteristics were described. Additionally,
      treatments, response to therapy, and survival outcomes were summarized. RESULTS:
      Of 1765 metastatic RCC patients in the clinical trials database, 10 had cardiac
      metastases without IVC involvement. All patients received treatment with targeted
      therapy. There was 1 observed partial response (10%) and 6 patients showed stable
      disease (60%). The median progression-free survival was 6.9 months. The
      systematic review of reported clinical cases included 39 patients. In these
      patients, the most common cardiac site of involvement was the right ventricle
      (51%; n = 20). Patients were treated with medical (28%; n = 11) and/or surgical
      treatment (49%; n = 19) depending on whether disease was isolated (n = 13) or
      multifocal (n = 26). CONCLUSION: To our knowledge, this is the first series to
      report on the presentation and outcomes of patients with cardiac metastasis
      without IVC involvement in RCC. We highlight that although the frequency of
      patients with cardiac metastases without IVC involvement is low, these patients
      have a unique clinical presentation and warrant special multidisciplinary
      management.

PMID- 29361426
TI  - Evaluation of a Patient With Temporomandibular Joint Disorders in Paget's Disease
      of Bone.

PMID- 29361427
TI  - Genomic characterisation of human monkeypox virus in Nigeria.

PMID- 29361428
TI  - Obesity and hypertension in Latin America: Current perspectives.
AB  - In the countries of Central America, South America and the Caribbean, there has
      been a dramatic rise in obesity, the metabolic syndrome, hypertension and other
      cardiovascular risk factors in the last few decades. Epidemiological evidence
      highlights a consistent correlation between obesity and hypertension, and the
      presence of obesity predisposes an individual to a greater risk of hypertension
      although the mechanisms remain unclear. Obesity and hypertension are two key
      drivers of the cardio-renal disease continuum, and patients with uncontrolled
      cardiovascular risk in their mid-life will likely have an increased risk of
      clinical cardiovascular and renal outcomes in old age. This article summarizes
      the current status for the prevalence and consequences of obesity and
      hypertension in Latin America, with the aim of initiating a call to action to all
      stakeholders for greater implementation of primary prevention strategies,
      particularly in the young.

PMID- 29361429
TI  - Sunitinib in patients with pre-treated pancreatic neuroendocrine tumors: A real
      world study.
AB  - INTRODUCTION: Besides data reported in a Phase-III trial, data on sunitinib in
      pancreatic Neuroendocrine Tumors (panNETs) are scanty. AIM: To evaluate sunitinib
      efficacy and tolerability in panNETs patients treated in a real-world setting.
      PATIENTS AND METHODS: Retrospective analysis of progressive panNETs treated with
      sunitinib. Efficacy was assessed by evaluating progression-free survival, overall
      survival, and disease control (DC) rate (stable disease (SD) + partial response +
      complete response). Data are reported as median (25th-75th IQR). RESULTS: Eighty
      patients were included. Overall, 71.1% had NET G2, 26.3% had NET G1, and 2.6% had
      NET G3 neoplasms. A total of 53 patients (66.3%) had received three or more
      therapeutic regimens before sunitinib, with 24 patients (30%) having been treated
      with four previous treatments. Median PFS was 10 months. Similar risk of
      progression was observed between NET G1 and NET G2 tumors (median PFS 11 months
      and 8 months, respectively), and between patients who had received >= 3 vs <= 2
      therapeutic approaches before sunitinib (median PFS 9 months and 10 months,
      respectively). DC rate was 71.3% and SD was the most frequent observed response,
      occurring in 43 pts (53.8%). Overall, 59 pts (73.8%) experienced AEs, which were
      grade 1-2 in 43 of them (72.9%), grade 3 in 15 pts (25.4%), and grade 4 in one
      patient (1.7%). Six pts (7.5%) stopped treatment due to toxicity. CONCLUSIONS:
      The present real-world experience shows that sunitinib is a safe and effective
      treatment for panNETs, even in the clinical setting of heavily pre-treated,
      progressive diseases.

PMID- 29361431
TI  - Peer Learning and Preserving the Physician's Right to Learn.

PMID- 29361430
TI  - Association between hypertension in adolescents and the health risk factors of
      their parents: an epidemiological family study.
AB  - Hypertension in adolescence may be a predictor of cardiovascular problems in
      adulthood. Therefore, verification of the factors associated with this condition
      in adolescence is important. The aim of this study was to analyze the
      relationship between hypertension in adolescents with hypertension and the
      sociodemographic characteristics and lifestyle of their parents. This study was
      conducted on 1231 adolescents, 1202 mothers, and 871 fathers. The blood pressure
      of the adolescents was measured with an oscillometric device. Details of parental
      hypertension, sociodemographic characteristics, and lifestyle were obtained by
      self-report. The prevalence of hypertension was higher among adolescents with
      older fathers and older mothers, with both parents reporting hypertension and
      with mothers who were overweight. In multivariable analysis, adolescents with
      older mothers (OR = 2.36; 95% confidence interval [CI] = 1.12-4.98), hypertensive
      mothers (OR = 2.22 [95% CI = 1.26-3.89]), and hypertensive fathers (OR = 1.70
      [95% CI = 1.03-2.81]) were more likely to have hypertension. In the analysis that
      considered clusters of health risk factors, higher risks of hypertension were
      observed in adolescents whose mothers had four or more aggregated risk factors
      (OR = 2.53 [95% CI = 1.11-5.74]). In conclusion, there was a relationship between
      hypertension in adolescents and hypertension in their parents. However, an
      association between hypertension in adolescents and parental age and clusters of
      health risk factors was only observed for their mothers.

PMID- 29361432
TI  - Research Priorities for Optimizing Geriatric Pharmacotherapy: An International
      Consensus.
AB  - Medication management is becoming increasingly challenging for older people, and
      there is limited evidence to guide medication prescribing and administration for
      people with multimorbidity, frailty, or at the end of life. Currently, there is a
      lack of clear research priorities in the field of geriatric pharmacotherapy. To
      address this issue, international experts from 5 research groups in geriatric
      pharmacotherapy and pharmacoepidemiology research were invited to attend the
      inaugural Optimizing Geriatric Pharmacotherapy through Pharmacoepidemiology
      Network workshop. A modified nominal group technique was used to explore and
      consolidate the priorities for conducting research in this field. Eight research
      priorities were elucidated: quality of medication use; vulnerable patient groups;
      polypharmacy and multimorbidity; person-centered practice and research;
      deprescribing; methodological development; variability in medication use; and
      national and international comparative research. The research priorities are
      discussed in detail in this article with examples of current gaps and future
      actions presented. These priorities highlight areas for future research in
      geriatric pharmacotherapy to improve medication outcomes in older people.

PMID- 29361434
TI  - The WelTel Trial in context and the importance of null findings.

PMID- 29361433
TI  - Effect of an interactive text-messaging service on patient retention during the
      first year of HIV care in Kenya (WelTel Retain): an open-label, randomised
      parallel-group study.
AB  - BACKGROUND: Retention of patients in HIV care is crucial to ensure timely
      treatment initiation, viral suppression, and to avert AIDS-related deaths. We did
      a randomised trial to determine whether a text-messaging intervention improved
      retention during the first year of HIV care. METHODS: This unmasked, randomised
      parallel-group study was done at two clinics in informal settlements in Nairobi,
      Kenya. Eligible participants were aged 18 years or older, HIV-positive, had their
      own mobile phone or access to one, and were able to use simple text messaging (or
      have somebody who could text message on their behalf). Participants were randomly
      assigned (1:1), with random block sizes of 2, 4, and 6, to the intervention or
      control group. Participants in the intervention group received a weekly text
      message from the automated WelTel service for 1 year and were asked to respond
      within 48 h. Participants in the control group did not receive text messages.
      Participants in both groups received usual care, which comprised psychosocial
      support and counselling; patient education; CD4 cell count; treatment; screening
      for tuberculosis, opportunistic infections, and sexually transmitted infections;
      prevention of mother-to-child transmission and family planning services; and up
      to two telephone calls for missed appointments. The primary outcome was retention
      in care at 12 months (ie, clinic attendance 10-14 months after the first visit).
      Participants who did not attend this 12-month appointment were traced, and we
      considered as retained those who were confirmed to be active in care elsewhere.
      The data analyst and clinic staff were masked to the group assignment, whereas
      participants and research nurses were not. We analysed the intention-to-treat
      population. This trial is registered with ClinicalTrials.gov, number NCT01630304.
      FINDINGS: Between April 4, 2013, and June 4, 2015, we screened 1068 individuals,
      of whom 700 were recruited. 349 people were allocated to the intervention group
      and 351 to the control group. Participants were followed up for a median of 55
      weeks (IQR 51-60). At 12 months, 277 (79%) of 349 participants in the
      intervention group were retained, compared with 285 (81%) of 351 participants in
      the control group (risk ratio 0.98, 95% CI 0.91-1.05; p=0.54). There was one mild
      adverse event related to the intervention, a domestic dispute that occurred when
      a participant's partner became suspicious of the weekly messages and follow-up
      calls. INTERPRETATION: This weekly text-messaging service did not improve
      retention of people in early HIV care. The intervention might have a modest role
      in improving self-perceived health-related quality of life in individuals in HIV
      care in similar settings. FUNDING: National Institutes of Health and Canadian
      Institutes of Health Research Canadian HIV Trials Network.

PMID- 29361436
TI  - The quest for optimal intraoperative colorectal cancer detection.

PMID- 29361435
TI  - Safety and effectiveness of SGM-101, a fluorescent antibody targeting
      carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a
      dose-escalation pilot study.
AB  - BACKGROUND: Tumour-targeted fluorescence imaging has the potential to advance
      current practice of oncological surgery by selectively highlighting malignant
      tissue during surgery. Carcinoembryonic antigen (CEA) is overexpressed in 90% of
      colorectal cancers and is a promising target for colorectal cancer imaging. We
      aimed to assess the tolerability of SGM-101, a fluorescent anti-CEA monoclonal
      antibody, and to investigate the feasibility to detect colorectal cancer with
      intraoperative fluorescence imaging. METHODS: We did an open-label, pilot study
      in two medical centres in the Netherlands. In the dose-escalation cohort, we
      included patients (aged >=18 years) with primary colorectal cancer with increased
      serum CEA concentrations (upper limit of normal of >=3 ng/mL) since diagnosis,
      who were scheduled for open or laparoscopic tumour resection. In the expansion
      cohort, we included patients (aged >=18 years) with recurrent or peritoneal
      metastases of colorectal cancer, with increasing serum concentrations of CEA
      since diagnosis, who were scheduled for open surgical resection. We did not mask
      patients, investigators, or anyone from the health-care team. We assigned
      patients using a 3 + 3 dose design to 5 mg, 7.5 mg, or 10 mg of SGM-101 in the
      dose-escalation cohort. In the expansion cohort, patients received a dose that
      was considered optimal at that moment of the study but not higher than the dose
      used in the dose-escalation cohort. SGM-101 was administered intravenously for 30
      min to patients 2 or 4 days before surgery. Intraoperative imaging was done to
      identify near-infrared fluorescent lesions, which were resected and assessed for
      fluorescence. The primary outcome was tolerability and safety of SGM-101,
      assessed before administration and continued up to 12 h after dosing, on the day
      of surgery, the first postoperative day, and follow-up visits at the day of
      discharge and the first outpatient clinic visit. Secondary outcomes were
      effectiveness of SGM-101 for detection of colorectal cancer, assessed by tumour
      to-background ratios (TBR); concordance between fluorescent signal and tumour
      status of resected tissue; and diagnostic accuracy in both cohorts. This trial is
      registered with the Nederlands Trial Register, number NTR5673, and
      ClinicalTrials.gov, number NCT02973672. FINDINGS: Between January, 2016, and
      February, 2017, 26 patients (nine in the dose-escalation cohort and 17 in the
      expansion cohort) were included in this study. SGM-101 did not cause any
      treatment-related adverse events, although three possibly related mild adverse
      events were reported in three (33%) of nine patients in the dose-escalation
      cohort and five were reported in three (18%) of 17 patients in the expansion
      cohort. Five moderate adverse events were reported in three (18%) patients in the
      expansion cohort, but they were deemed unrelated to SGM-101. No changes in vital
      signs, electrocardiogram, or laboratory results were found after administration
      of the maximum dose of 10 mg of SGM-101 in both cohorts. A dose of 10 mg,
      administered 4 days before surgery, showed the highest TBR (mean TBR 6.10 [SD
      0.42] in the dose-escalation cohort). In the expansion cohort, 19 (43%) of 43
      lesions were detected using fluorescence imaging and were not clinically
      suspected before fluorescent detection, which changed the treatment strategy in
      six (35%) of 17 patients. Sensitivity was 98%, specificity was 62%, and accuracy
      of fluorescence intensity was 84% in the expansion cohort. INTERPRETATION: This
      study presents the first clinical use of CEA-targeted detection of colorectal
      cancer and shows that SGM-101 is safe and can influence clinical decision making
      during the surgical procedure for patients with colorectal cancer. FUNDING:
      Surgimab.

PMID- 29361438
TI  - Comparison of anxiety and child-care education characteristics of mothers who
      have children with or without speech delays.
AB  - INTRODUCTION: Speech delay in a child could be the cause and/or result of the
      emotional disorder. The child rearing attitude that the parents have accepted
      could have both positive and negative effects on the personality of the child.
      OBJECTIVE: The current study aimed to investigate the sociodemographic features
      and the mothers' anxiety of children with speech delay. METHODS: One hundred five
      mothers with children aged between 3 and 6 years with speech delays were included
      in the patient group, and 105 mothers who have children aged between 3 and 6
      years with normal speech and language development were included in the control
      group. An information form questionnaire including demographic characteristics,
      the Family Life and Childrearing Attitude Scale (PARI - Parental Attitude
      Research Instrument) and beck anxiety scale were requested from all mothers in
      the patient and the control groups. RESULTS: In the current study, there was a
      significant difference between the groups in terms of gender (p=0.001). According
      to Parental Attitude Research Instrument, the mean of mothers of the children
      with speech delays was higher than the mean of mothers of normal children in
      terms of the answers to overprotective mother aspect (p<0.01). The mothers of
      children with speech delays had more overprotective motherhood attitudes;
      however, the difference in terms of the answers to the aspects of democratic
      attitude and provision of equality, refusal to be a housewife, husband-wife
      conflict, and suppression and discipline were not statistically significant. The
      beck anxiety scale, a significant difference was detected between the two groups
      (p<0.01). It was found that the mothers of children with speech delays had more
      severe levels of anxiety. CONCLUSION: The social structure of the family, the
      attitudes and the behaviors of the mother, and the anxiety levels of the mothers
      have important effects on child development. Thus, it is necessary to perform
      further studies related to speech delays, in which many factors play a role in
      the etiology.

PMID- 29361437
TI  - Effect of caffeine on vestibular evoked myogenic potential: a systematic review
      with meta-analysis.
AB  - INTRODUCTION: Caffeine can be considered the most consumed drug by adults
      worldwide, and can be found in several foods, such as chocolate, coffee, tea,
      soda and others. Overall, caffeine in moderate doses, results in increased
      physical and intellectual productivity, increases the capacity of concentration
      and reduces the time of reaction to sensory stimuli. On the other hand, high
      doses can cause noticeable signs of mental confusion and error induction in
      intellectual tasks, anxiety, restlessness, muscle tremors, tachycardia,
      labyrinthine changes, and tinnitus. OBJECTIVE: Considering that the vestibular
      evoked myogenic potential is a clinical test that evaluates the muscular response
      of high intensity auditory stimulation, the present systematic review aimed to
      analyze the effects of caffeine on vestibular evoked myogenic potential. METHODS:
      This study consisted of the search of the following databases: MEDLINE, CENTRAL,
      ScienceDirect, Scopus, Web of Science, LILACS, SciELO and ClinicalTrials.gov.
      Additionally, the gray literature was also searched. The search strategy included
      terms related to intervention (caffeine or coffee consumption) and the primary
      outcome (vestibular evoked myogenic potential). RESULTS: Based on the 253
      potentially relevant articles identified through the database search, only two
      full-text publications were retrieved for further evaluation, which were
      maintained for qualitative analysis. CONCLUSION: Analyzing the articles found,
      caffeine has no effect on vestibular evoked myogenic potential in normal
      individuals.

PMID- 29361439
TI  - Emergency endoscopic needle-knife precut papillotomy in acute severe cholangitis
      resulting from impacted common bile duct stones at duodenal papilla.
AB  - AIM: To evaluate the efficacy and safety of emergency endoscopic needle-knife
      precut papillotomy in acute severe cholangitis resulting from impacted common
      bile duct stones at duodenal papilla. METHODS: Between January 2010 and January
      2015, 118 cases of acute severe cholangitis with impacted common bile duct stones
      at the native papilla underwent emergency endoscopic retrograde
      cholangiopancreatography (ERCP) and early needle-knife precut papillotomy in a
      tertiary referral center. Precut techniques were performed according to the
      different locations of stones in the duodenal papilla. Clinical data about
      therapy and recovery of the 118 patients were recorded and analyzed. RESULTS: One
      hundred and eighteen patients underwent emergency ERCP within 24 h after
      hospitalization, with a total success rate of 100%. The mean operating time was
      6.4 +/- 4.1 min. Postoperative acute physiology and chronic health evaluation
      (APACHE) II scores, white blood cell count and liver function improved
      significantly. The complication rate was 4.2% (5/118); two with hemorrhage and
      three with acute pancreatitis. There was no procedure-related mortality.
      CONCLUSION: Emergency endoscopic needle-knife precut papillotomy is effective and
      safe for acute severe cholangitis resulting from impacted common bile duct stones
      at the duodenal papilla.

PMID- 29361440
TI  - International consensus (ICON) on comprehensive management of the laryngeal
      nerves risks during thyroid surgery.
AB  - The laryngeal monitoring of the inferior and superior laryngeal nerves, and the
      vagus nerve, has advanced for last years, in practice of thyroid and parathyroid
      surgery. Different methods are used, using direct or indirect laryngeal
      stimulation and also intermittent or continuous nerve registration. At present
      time, various recommendations of it in the world use are reported, and
      availability of the tool used remains a limit in some countries. The aim of this
      Icon during Ifos 2017 was to share knowledge about laryngeal intraoperative nerve
      monitoring (LIONM) procedures and to evaluate current practices used to improve
      the quality of thyroid and parathyroid surgery. Benefits of LIONM were discussed
      with three experts (Pr G. Randolph from Boston, Pr Henning Dralle from Halle in
      Germany, Pr Hoon Yub KIM from Seoul). All of them have been actively involved in
      the development and use of laryngeal nerve monitoring during thyroid and
      parathyroid surgery.

PMID- 29361441
TI  - Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation
      (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study
      and review.
AB  - BACKGROUND: Electrical stimulation of the auricular branch of the vagus nerve
      (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence
      afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with
      inconsistent findings due to variability in stimulation targets and parameters.
      OBJECTIVE: We developed a taVNS/fMRI system to enable concurrent electrical
      stimulation and fMRI acquisition to compare the effects of taVNS in relation to
      control stimulation. METHODS: We enrolled 17 healthy adults in this single-blind,
      crossover taVNS/fMRI trial. Based on parameters shown to affect heart rate in
      healthy volunteers, participants received either left tragus (active) or earlobe
      (control) stimulation at 500 MUs 25 HZ for 60 s (repeated 3 times over 6 min).
      Whole brain fMRI analysis was performed exploring the effect of: active
      stimulation, control stimulation, and the comparison. Region of interest analysis
      of the midbrain and brainstem was also conducted. RESULTS: Active stimulation
      produced significant increased BOLD signal in the contralateral postcentral
      gyrus, bilateral insula, frontal cortex, right operculum, and left cerebellum.
      Control stimulation produced BOLD signal activation in the contralateral
      postcentral gyrus. In the active vs. control contrast, tragus stimulation
      produced significantly greater BOLD increases in the right caudate, bilateral
      anterior cingulate, cerebellum, left prefrontal cortex, and mid-cingulate.
      CONCLUSION: Stimulation of the tragus activates the cerebral afferents of the
      vagal pathway and combined with our review of the literature suggest that taVNS
      is a promising form of VNS. Future taVNS/fMRI studies should systematically
      explore various parameters and alternative stimulation targets aimed to optimize
      this novel form of neuromodulation.

PMID- 29361442
TI  - Effects of TDCS dosage on working memory in healthy participants.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) has been found to
      improve working memory (WM) performance in healthy participants following a
      single session. However, results are mixed and the overall effect size is small.
      Interpretation of these results is confounded by heterogeneous study designs,
      including differences in tDCS dose (current intensity) and sham conditions used.
      AIMS: We systematically investigated the effect of tDCS dose on working memory
      using behavioural and neurophysiological outcomes. METHODS: In a single-blind
      parallel group design, 100 participants were randomised across five groups to
      receive 15 min of bifrontal tDCS at different current intensities (2 mA, 1 mA,
      and three sham tDCS conditions at 0.034 mA, 0.016 mA, or 0 mA). EEG activity was
      acquired while participants performed a WM task prior to, during, and following
      tDCS. Response time, accuracy and an event-related EEG component (P3) were
      evaluated. RESULTS: We found no significant differences in response time or
      performance accuracy between current intensities. The P3 amplitude was
      significantly lower in the 0 mA condition compared to the 0.034 mA, 1 mA and 2 mA
      tDCS conditions. Changes in WM accuracy were moderately correlated with changes
      in frontal P3 amplitude (channel Fz) following tDCS compared to baseline levels
      (r = 0.34). CONCLUSIONS: Working memory was not significantly altered by tDCS,
      regardless of dose. The P3 amplitude showed that stimulation at 1 mA, 2 mA and a
      sham condition (0.034 mA) had biological effects, with the largest effect size
      for 1 mA stimulation. These findings indicate higher sensitivity of
      neurophysiological outcomes to tDCS and suggests that sham stimulation previously
      considered inactive may alter neuronal function.

PMID- 29361443
TI  - The 0.035-Inch Wire Externalization Technique for Overcoming a Severely Angled
      and Calcified Aortic Bifurcation.

PMID- 29361444
TI  - Prognostic Implication of Functional Incomplete Revascularization and Residual
      Functional SYNTAX Score in Patients With Coronary Artery Disease.
AB  - OBJECTIVES: The aim of this study was to investigate the prognostic implication
      of functional incomplete revascularization (IR) and residual functional SYNTAX
      (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac
      Surgery) score (rFSS) in comparison with 3-vessel fractional flow reserve (FFR)
      and residual SYNTAX score. BACKGROUND: IR is associated with poor clinical
      outcomes in patients who underwent percutaneous coronary intervention. METHODS: A
      total of 385 patients who underwent 3-vessel FFR measurement after stent
      implantation were included in this study. The rFSS was defined as residual SYNTAX
      score measured only in vessels with FFR <=0.8. The study population was divided
      into the functional IR group (rFSS >=1) and the functional complete
      revascularization (CR) group (rFSS = 0). The primary outcome was major adverse
      cardiac events (MACEs; a composite of cardiac death, myocardial infarction, and
      ischemia-driven revascularization) at 2 years. RESULTS: Functional CR was
      achieved in 283 patients (73.5%). At 2-year follow-up, the functional IR group
      showed a significantly higher risk for MACEs (functional IR vs. CR, 14.6% vs.
      4.2%; hazard ratio: 4.09; 95% confidence interval: 1.82 to 9.21; p < 0.001) than
      the functional CR group. In a multivariate-adjusted model, functional IR was an
      independent predictor of MACEs (adjusted hazard ratio: 4.17; 95% confidence
      interval: 1.85 to 9.44; p < 0.001). The rFSS showed a significant association
      with estimated 2-year MACE rate (hazard ratio: 1.09 per 1-U increase; 95%
      confidence interval: 1.02 to 1.17; p = 0.018). When added to clinical risk
      factors, rFSS showed the highest integrated discrimination improvement value for
      MACEs (3.5%; p = 0.002) among 3-vessel FFR, residual SYNTAX score, and rFSS.
      CONCLUSIONS: Patients with functional IR showed significantly higher rate of 2
      year MACEs than those with functional CR. A combined anatomic and physiological
      scoring system (rFSS) after stent implantation better discriminated the risk for
      adverse events than anatomic or physiological assessment alone. (Clinical
      Implication of 3-Vessel Fractional Flow Reserve [FFR]; NCT01621438).

PMID- 29361445
TI  - Clipping the Ring: Transcatheter Edge-to-Ring Mitral Valve Repair in a Patient
      With Prior Mitral Annuloplasty Ring.

PMID- 29361446
TI  - 3-Dimensional-Printed Model for Planning Transcatheter Mitral Valve Replacement.

PMID- 29361447
TI  - A Novel Angiographic Quantification of Aortic Regurgitation After TAVR Provides
      an Accurate Estimation of Regurgitation Fraction Derived From Cardiac Magnetic
      Resonance Imaging.
AB  - OBJECTIVES: This study sought to compare a new quantitative angiographic
      technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF)
      for the quantification of prosthetic valve regurgitation (PVR) after
      transcatheter aortic valve replacement (TAVR). BACKGROUND: PVR after TAVR is
      challenging to quantify, especially during the procedure. METHODS: Post
      replacement aortograms in 135 TAVR recipients were analyzed offline by
      videodensitometry to measure the ratio of the time-resolved contrast density in
      the left ventricular outflow tract to that in the aortic root (videodensitometric
      aortic regurgitation [VD-AR]). CMR was performed within an interval of <=30 days
      (11 +/- 6 days) after the procedure. RESULTS: The average CMR-RF was 6.7 +/- 7.0%
      whereas the average VD-AR was 7.0 +/- 7.0%. The correlation between VD-AR and CMR
      RF was substantial (r = 0.78, p < 0.001). On receiver-operating characteristic
      curves, a VD-AR >=10% corresponded to >mild PVR as defined by CMR-RF (area under
      the curve: 0.94; p < 0.001; sensitivity 100%, specificity 83%), whereas a VD-AR
      >=25% corresponded to moderate-to-severe PVR (area under the curve: 0.99; p =
      0.004; sensitivity 100%, specificity 98%). Intraobserver reproducibility was
      excellent for both techniques (for CMR-RF, intraclass correlation coefficient:
      0.91, p < 0.001; for VD-AR intraclass correlation coefficient: 0.93, p < 0.001).
      The difference on rerating was -0.04 +/- 7.9% for CMR-RF and -0.40 +/- 6.8% for
      VD-AR. CONCLUSIONS: The angiographic VD-AR provides a surrogate assessment of PVR
      severity after TAVR that correlates well with the CMR-RF.

PMID- 29361448
TI  - Angiographic or Functional Success?: Rethinking the Goal of Percutaneous Coronary
      Intervention.

PMID- 29361449
TI  - Transcatheter Tricuspid Valve Repair With the PASCAL System.

PMID- 29361450
TI  - Thrombotic Occlusion and Revascularization of a Left Main Coronary Artery
      Aneurysm Years After Surgical Closure of Left Coronary-to-Right Ventricle
      Fistula.

PMID- 29361451
TI  - Quantifying Paravalvular Aortic Regurgitation in Transcatheter Aortic Valve
      Replacement: The Pursuit of Perfection.

PMID- 29361452
TI  - Should we continue to measure endometrial thickness in modern-day medicine? The
      effect on live birth rates and birth weight.
AB  - The evaluation of endometrial thickness (EMT) is still part of standard cycle
      monitoring during IVF, despite the lack of robust evidence of any value of this
      measurement to predict little revalidation in contemporary medical practice;
      other tools, however, such as endocrine profile monitoring, have become
      increasingly popular. The aim of this study was to reassess whether EMT affects
      the outcome of a fresh embryo transfer in modern-day medicine, using a
      retrospective, single-centre cohort of 3350 IVF cycles (2827 women) carried out
      between 2010 and 2014. In the multivariate regression analysis, EMT was non
      linearly associated with live birth, with live birth rates being the lowest with
      an EMT less than 7.0 mm (21.6%; P < 0.001) and then between 7.0 mm and 9.0 mm
      (30.2%; P = 0.008). An EMT less than 7.0 mm was also associated with a decrease
      in neonatal birthweight z-scores (-0.40; 95% CI -0.69 to -0.12). In conclusion,
      these results reaffirm the use of EMT as a potential prognostic tool for live
      birth rates and neonatal birthweight in contemporary IVF, namely when considered
      together with other ovarian stimulation monitoring methods, such as the late
      follicular endocrine profile.

PMID- 29361453
TI  - Lower follicular fluid vitamin D concentration is related to a higher number of
      large ovarian follicles.
AB  - Vitamin D receptor-knockout mice fail to produce mature oocytes, indicating
      vitamin D is crucial for folliculogenesis in mice. However, the actions of
      vitamin D during folliculogenesis remain unknown. This prospective study aimed to
      assess whether follicular fluid (FF) vitamin D (25OHD3) concentrations are
      related to specific responses to ovarian stimulation. Women undergoing ovarian
      stimulation for IVF participated in the study. FF 25OHD3 concentrations were
      assessed in the first follicle aspirate on oocyte retrieval day. Oestradiol and
      progesterone concentrations were assessed on the trigger day. K-means grouping
      analysis showed that 25OHD3 FF concentrations clustered into a higher and lower
      group (mean +/- SEM 17.4 +/- 6.61 ng/ml and 35.5 +/- 7.17 ng/ml, respectively, P
      < 0.001). The clusters were analysed according to the oestradiol and progesterone
      concentrations, follicle number and size and resulting oocyte number and
      maturity. The FF 25OHD3 concentrations were no different among the infertility
      diagnoses. The lower 25OHD3 group had more follicles (>=16.0 mm, P = 0.009) and
      higher serum oestradiol concentrations (P < 0.03) on the day of HCG
      administration. In this study, lower follicular 25OHD3 concentrations predicted a
      better response to ovarian stimulation shown by a greater production of larger
      follicles and higher serum oestradiol concentrations.

PMID- 29361454
TI  - Interleukin 11 blockade during mid to late gestation does not affect maternal
      blood pressure, pregnancy viability or subsequent fertility in mice.
AB  - Interleukin (IL)11 is a crucial regulator during the initiation of pregnancy in
      humans and mice. Elevated levels are detected in serum, placenta and decidua of
      women with pre-eclampsia. Elevated IL11 during placentation recapitulates pre
      eclampsia in mice, although withdrawal rescues pre-eclampsia features, suggesting
      that IL11 could provide a novel therapeutic target. The aim of this study was to
      determine the safety profile of an IL11 antagonist ligated to polyethylene glycol
      (PEGIL11A) during pregnancy in mice. Blocking IL11 signalling during mid to late
      gestation pregnancy in mice did not affect pregnancy viability, or alter
      placental or fetal weight, or morphology. Importantly, decidual area remained
      unchanged. PEGIL11A did not affect maternal blood pressure, urinary protein or
      term pup weight. PEGIL11A administration to non-pregnant mice did not affect
      subsequent fertility; there was no difference in number of implantation sites, or
      placental or fetal weight between PEGIL11A and PEG-treated mice. These data show
      that blocking IL11Ralpha during placentation does not alter the placenta,
      decidua, fetus, maternal blood pressure or kidneys. These findings highlight the
      potential of IL11 signalling inhibition as a safe therapy to alleviate pre
      eclampsia symptoms and demonstrate the potential for IL11 inhibition as a novel
      fertility-preserving therapy for women with cancer.

PMID- 29361455
TI  - Tension Pneumothorax During One-Lung Ventilation - An Underestimated
      Complication?

PMID- 29361456
TI  - The Combination of Diameters of Cricoid Ring and Left Main Bronchus for Selecting
      the "Best Fit" Double-Lumen Tube.
AB  - OBJECTIVES: The aims of this study were to measure diameters of the cricoid ring
      and left main bronchus in Asian adult patients and to assess the accuracy of
      double lumen tube size selected according to cricoid and left main bronchus
      diameter, respectively. DESIGN: Retrospective observational study. SETTING:
      Academic, tertiary care hospital. PARTICIPANTS: Preoperative CT scans from 87 men
      and 94 women who had undergone general anesthesia for lung operations.
      INTERVENTIONS: No intervention. MEASUREMENTS AND MAIN RESULTS: The diameters of
      the cricoid ring and left main bronchus were measured from thoracic computed
      tomography images after correction of slant. The "best-fit" size of double lumen
      tube was determined by comparing diameter of the left main bronchus and cricoid
      ring with the diameter of the double lumen tube. Diameters of the cricoid ring
      and left main bronchus were both significantly greater in men compared with women
      (p < 0.0001). Shapes of cricoid rings were different between genders (p <
      0.0001), while shapes of the left main bronchus were not significant different (p
      = 0.343). With reference to the "best fit" size, the rate of agreement of cricoid
      ring size, left main bronchus size, and height size for men were 100%, 100%, and
      94.3%. For women, the rate of agreement of cricoid ring size, left main bronchus
      size, and height size were 94.7%, 63.8%, and 51.1%. CONCLUSIONS: The "best fit"
      size of a double lumen tube should be decided by a combination of diameters of
      the cricoid ring and the left main bronchus.

PMID- 29361457
TI  - Postoperative Delirium in Cardiac Surgery Patients.
AB  - OBJECTIVE: The authors studied the incidence of postoperative delirium among
      cardiac surgery patients using the Intensive Care Delirium Screening Checklist
      (ICDSC). DESIGN: Prospective screening. SETTING: Two university hospitals.
      PARTICIPANTS: A total of 1,036 consecutive patients. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Patients were prospectively screened from day 1 to
      day 10 after surgery or until hospital discharge. Appropriate perioperative data
      were collected. The overall incidence of postoperative delirium was 11.5%. In the
      multivariate logistic regression analysis, age over 70 years, higher EuroSCORE
      points, longer aortic occlusion time, and profuse drainage increased the
      incidence of delirium. The duration of mechanical ventilation and intensive care
      unit length of stay were longer in the group of patients with delirium (10.6
      hours [6.6-19.5] v 6.4 hours [4.9-8.6], p < 0.001, and 1.7 days [0.9-4.2] v 0.9
      days [0.9-1], p < 0.001). CONCLUSIONS: Postoperative delirium is common after
      cardiac surgery, and it is associated with the duration of mechanical
      ventilation.

PMID- 29361458
TI  - Hypoxia During One-Lung Ventilation-A Review and Update.

PMID- 29361459
TI  - Extended use of bemiparin as thromboprophylaxis during bariatric surgery: results
      of anti-factor Xa activity measurements.
AB  - BACKGROUND: The incidence of venous thromboembolism (VTE) in morbidly obese
      patients after obesity surgery is between .2% and 3.5%. Because there are a lack
      of prospective studies on the type of drug, the correct dosage, and the optimal
      duration, there are no specific recommendations found in the guidelines on
      thrombophylaxis. OBJECTIVES: To compare the incidence of VTE and hemorrhagic
      events in bariatric surgical patients receiving bemiparin thromboprophylaxis who
      have prophylactic and nonprophylactic Anti-factor Xa (AFXa) levels. SETTING:
      University General Hospital of Ciudad Real, Spain, public practice. METHODS: A
      cohort study of 122 morbidly obese patients who underwent bariatric surgery. The
      thromboprophylactic regimen consisted of bemiparin 5000 IU/24 hr for 30 days.
      AFXa levels were measured on the second and third day postoperation (prophylactic
      range: .3-.5 IU/mL). Body mass index, co-morbidities, prothrombotic risk factors,
      and thrombotic and hemorrhagic events were noted. RESULTS: The mean body mass
      index was 48.4 kg/m2. In 50 samples, the level of AFXa was within the
      prophylactic range; in 71, they were in the subprophylactic range. No VTEs were
      observed. Major hemorrhagic events were observed in 2.4%. We did not find a
      significant association between AFXa and thromboembolic and hemorrhagic events.
      There is a significant negative correlation between the level of AFXa and body
      mass index. CONCLUSION: A regimen of 5000 IU/24 hr of bemiparin for 30 days after
      obesity surgery appears to prevent VTE without increasing the risk of a major
      hemorrhage. The level of AFXa is not associated with postoperative thrombotic or
      hemorrhagic events occurring after bariatric surgery.

PMID- 29361460
TI  - Corrections.

PMID- 29361461
TI  - Germany's delayed coal phase-out and respiratory health.

PMID- 29361462
TI  - Safety and efficacy of tiotropium in children aged 1-5 years with persistent
      asthmatic symptoms: a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Few studies have assessed the safety and efficacy of potential asthma
      medications in children younger than 5 years. We descriptively assessed the
      safety and efficacy of tiotropium, a long-acting anticholinergic drug, in
      children aged 1-5 years with persistent asthmatic symptoms. METHODS: This
      exploratory 12-week, randomised, double-blind, placebo-controlled, parallel
      group, phase 2/3, regulatory multicentre trial was done at 32 hospitals, clinics,
      and clinical research units in 11 countries in Asia, Europe, and North America.
      Children aged 1-5 years with at least a 6-month history of persistent asthmatic
      symptoms and a need for inhaled corticosteroids were eligible. Patients were
      randomly allocated using an interactive voice or web-based response system to
      receive once-daily tiotropium 2.5 MUg, tiotropium 5 MUg, or placebo as an add-on
      to inhaled corticosteroids with or without additional controller medication.
      Patients and investigators were masked to study group assignment. Tiotropium was
      given via the Respimat inhaler once daily as two puffs of 1.25 MUg in the 2.5 MUg
      group, two puffs of 2.5 MUg in the 5 MUg group, or two puffs of placebo. The
      primary outcomes were safety, which was assessed by comparing adverse events
      between the tiotropium and placebo groups, and efficacy, which was measured as
      the change in weekly mean combined daytime asthma symptom score from baseline to
      week 12. Statistical analyses of treatment effects were exploratory; although
      endpoints were defined, they were used for descriptive analyses only. The safety
      and primary analyses were done in all patients who received at least one dose of
      their assigned treatment. This study is registered with ClinicalTrials.gov
      (NCT01634113), and is completed. FINDINGS: Between July 26, 2012, and Dec 4,
      2014, 102 children were randomly assigned to the three treatment groups (36 to
      receive tiotropium 2.5 MUg, 32 to receive tiotropium 5 MUg, and 34 to receive
      placebo). 101 children completed the study and were included in the analyses. The
      changes in adjusted weekly mean combined daytime asthma symptom scores between
      baseline and week 12 were not significantly different between any of the groups.
      The adjusted mean difference between the tiotropium 2.5 MUg group and placebo
      group was -0.080 (95% CI -0.312 to 0.152) and the difference between tiotropium 5
      MUg and placebo group was -0.048 (-0.292 to 0.195). Adverse events were less
      frequent with tiotropium treatment than with placebo (20 [56%] of 36 children
      with tiotropium 2.5 MUg, 18 [58%] of 31 with tiotropium 5 MUg, and 25 [74%] of 34
      with placebo), although no formal statistical comparison between groups was
      performed. A greater proportion of children reported asthma exacerbations as
      adverse events in the placebo group (ten [29%] of 34) than in the tiotropium
      groups (five [14%] of 36 in the 2.5 MUg group and two [6%] of 31 in the 5 MUg
      group). Serious adverse events were reported in three patients (all of whom
      received placebo); no adverse events led to discontinuation of treatment or
      death. INTERPRETATION: To our knowledge, our small study is the first to assess
      the safety and efficacy of tiotropium in children aged 1-5 years with persistent
      asthmatic symptoms. Tolerability of tiotropium was similar to that of placebo,
      which is consistent with previous findings in older populations. Although mean
      daytime asthma symptom scores were not significantly different between groups,
      tiotropium showed the potential to reduce asthma exacerbation risk compared with
      placebo. The findings of the study are limited by the small sample size and
      descriptive statistical analyses. Additional well powered trials are needed to
      further assess the safety and efficacy of tiotropium in young children. FUNDING:
      Boehringer Ingelheim.

PMID- 29361463
TI  - Tiotropium: from COPD to young children with asthma?

PMID- 29361465
TI  - Unification of Protein Abundance Datasets Yields a Quantitative Saccharomyces
      cerevisiae Proteome.
AB  - Protein activity is the ultimate arbiter of function in most cellular pathways,
      and protein concentration is fundamentally connected to protein action. While the
      proteome of yeast has been subjected to the most comprehensive analysis of any
      eukaryote, existing datasets are difficult to compare, and there is no consensus
      abundance value for each protein. We evaluated 21 quantitative analyses of the S.
      cerevisiae proteome, normalizing and converting all measurements of protein
      abundance into the intuitive measurement of absolute molecules per cell. We
      estimate the cellular abundance of 92% of the proteins in the yeast proteome and
      assess the variation in each abundance measurement. Using our protein abundance
      dataset, we find that a global response to diverse environmental stresses is not
      detected at the level of protein abundance, we find that protein tags have only a
      modest effect on protein abundance, and we identify proteins that are
      differentially regulated at the mRNA abundance, mRNA translation, and protein
      abundance levels.

PMID- 29361464
TI  - Integration of Multi-omics Data from Mouse Diversity Panel Highlights
      Mitochondrial Dysfunction in Non-alcoholic Fatty Liver Disease.
AB  - The etiology of non-alcoholic fatty liver disease (NAFLD), the most common form
      of chronic liver disease, is poorly understood. To understand the causal
      mechanisms underlying NAFLD, we conducted a multi-omics, multi-tissue integrative
      study using the Hybrid Mouse Diversity Panel, consisting of ~100 strains of mice
      with various degrees of NAFLD. We identified both tissue-specific biological
      processes and processes that were shared between adipose and liver tissues. We
      then used gene network modeling to predict candidate regulatory genes of these
      NAFLD processes, including Fasn, Thrsp, Pklr, and Chchd6. In vivo knockdown
      experiments of the candidate genes improved both steatosis and insulin
      resistance. Further in vitro testing demonstrated that downregulation of both
      Pklr and Chchd6 lowered mitochondrial respiration and led to a shift toward
      glycolytic metabolism, thus highlighting mitochondria dysfunction as a key
      mechanistic driver of NAFLD.

PMID- 29361466
TI  - Integrative Personal Omics Profiles during Periods of Weight Gain and Loss.
AB  - Advances in omics technologies now allow an unprecedented level of phenotyping
      for human diseases, including obesity, in which individual responses to excess
      weight are heterogeneous and unpredictable. To aid the development of better
      understanding of these phenotypes, we performed a controlled longitudinal weight
      perturbation study combining multiple omics strategies (genomics,
      transcriptomics, multiple proteomics assays, metabolomics, and microbiomics)
      during periods of weight gain and loss in humans. Results demonstrated that: (1)
      weight gain is associated with the activation of strong inflammatory and
      hypertrophic cardiomyopathy signatures in blood; (2) although weight loss
      reverses some changes, a number of signatures persist, indicative of long-term
      physiologic changes; (3) we observed omics signatures associated with insulin
      resistance that may serve as novel diagnostics; (4) specific biomolecules were
      highly individualized and stable in response to perturbations, potentially
      representing stable personalized markers. Most data are available open access and
      serve as a valuable resource for the community.

PMID- 29361467
TI  - Scikit-ribo Enables Accurate Estimation and Robust Modeling of Translation
      Dynamics at Codon Resolution.
AB  - Ribosome profiling (Ribo-seq) is a powerful technique for measuring protein
      translation; however, sampling errors and biological biases are prevalent and
      poorly understood. Addressing these issues, we present Scikit-ribo
      (https://github.com/schatzlab/scikit-ribo), an open-source analysis package for
      accurate genome-wide A-site prediction and translation efficiency (TE) estimation
      from Ribo-seq and RNA sequencing data. Scikit-ribo accurately identifies A-site
      locations and reproduces codon elongation rates using several digestion protocols
      (r = 0.99). Next, we show that the commonly used reads per kilobase of transcript
      per million mapped reads-derived TE estimation is prone to biases, especially for
      low-abundance genes. Scikit-ribo introduces a codon-level generalized linear
      model with ridge penalty that correctly estimates TE, while accommodating
      variable codon elongation rates and mRNA secondary structure. This corrects the
      TE errors for over 2,000 genes in S. cerevisiae, which we validate using mass
      spectrometry of protein abundances (r = 0.81), and allows us to determine the
      Kozak-like sequence directly from Ribo-seq. We conclude with an analysis of
      coverage requirements needed for robust codon-level analysis and quantify the
      artifacts that can occur from cycloheximide treatment.

PMID- 29361468
TI  - Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in
      patients with high-risk, surgically resectable melanoma: a single-centre, open
      label, randomised, phase 2 trial.
AB  - BACKGROUND: Dual BRAF and MEK inhibition produces a response in a large number of
      patients with stage IV BRAF-mutant melanoma. The existing standard of care for
      patients with clinical stage III melanoma is upfront surgery and consideration
      for adjuvant therapy, which is insufficient to cure most patients. Neoadjuvant
      targeted therapy with BRAF and MEK inhibitors (such as dabrafenib and trametinib)
      might provide clinical benefit in this high-risk p opulation. METHODS: We
      undertook this single-centre, open-label, randomised phase 2 trial at the
      University of Texas MD Anderson Cancer Center (Houston, TX, USA). Eligible
      participants were adult patients (aged >=18 years) with histologically or
      cytologically confirmed surgically resectable clinical stage III or
      oligometastatic stage IV BRAFV600E or BRAFV600K (ie, Val600Glu or Val600Lys)
      mutated melanoma. Eligible patients had to have an Eastern Cooperative Oncology
      Group performance status of 0 or 1, a life expectancy of more than 3 years, and
      no previous exposure to BRAF or MEK inhibitors. Exclusion criteria included
      metastases to bone, brain, or other sites where complete surgical excision was in
      doubt. We randomly assigned patients (1:2) to either upfront surgery and
      consideration for adjuvant therapy (standard of care group) or neoadjuvant plus
      adjuvant dabrafenib and trametinib (8 weeks of neoadjuvant oral dabrafenib 150 mg
      twice per day and oral trametinib 2 mg per day followed by surgery, then up to 44
      weeks of adjuvant dabrafenib plus trametinib starting 1 week after surgery for a
      total of 52 weeks of treatment). Randomisation was not masked and was implemented
      by the clinical trial conduct website maintained by the trial centre. Patients
      were stratified by disease stage. The primary endpoint was investigator-assessed
      event-free survival (ie, patients who were alive without disease progression) at
      12 months in the intent-to-treat population. This trial is registered at
      ClinicalTrials.gov, number NCT02231775. FINDINGS: Between Oct 23, 2014, and April
      13, 2016, we randomly assigned seven patients to standard of care, and 14 to
      neoadjuvant plus adjuvant dabrafenib and trametinib. The trial was stopped early
      after a prespecified interim safety analysis that occurred after a quarter of the
      participants had been accrued revealed significantly longer event-free survival
      with neoadjuvant plus adjuvant dabrafenib and trametinib than with standard of
      care. After a median follow-up of 18.6 months (IQR 14.6-23.1), significantly more
      patients receiving neoadjuvant plus adjuvant dabrafenib and trametinib were alive
      without disease progression than those receiving standard of care (ten [71%] of
      14 patients vs none of seven in the standard of care group; median event-free
      survival was 19.7 months [16.2-not estimable] vs 2.9 months [95% CI 1.7-not
      estimable]; hazard ratio 0.016, 95% CI 0.00012-0.14, p<0.0001). Neoadjuvant plus
      adjuvant dabrafenib and trametinib were well tolerated with no occurrence of
      grade 4 adverse events or treatment-related deaths. The most common adverse
      events in the neoadjuvant plus adjuvant dabrafenib and trametinib group were
      expected grade 1-2 toxicities including chills (12 patients [92%]), headache (12
      [92%]), and pyrexia (ten [77%]). The most common grade 3 adverse event was
      diarrhoea (two patients [15%]). INTERPRETATION: Neoadjuvant plus adjuvant
      dabrafenib and trametinib significantly improved event-free survival versus
      standard of care in patients with high-risk, surgically resectable, clinical
      stage III-IV melanoma. Although the trial finished early, limiting
      generalisability of the results, the findings provide proof-of-concept and
      support the rationale for further investigation of neoadjuvant approaches in this
      disease. This trial is currently continuing accrual as a single-arm study of
      neoadjuvant plus adjuvant dabrafenib and trametinib. FUNDING: Novartis
      Pharmaceuticals Corporation.

PMID- 29361471
TI  - A turning point in the fight against ovarian cancer?

PMID- 29361469
TI  - Patients with melanoma treated with an anti-PD-1 antibody beyond RECIST
      progression: a US Food and Drug Administration pooled analysis.
AB  - BACKGROUND: Patients who receive immunotherapeutic drugs might develop an
      atypical response pattern, wherein they initially meet conventional response
      criteria for progressive disease but later have decreases in tumour burden. Such
      responses warrant further investigation into the potential benefits and risks for
      patients who continue immunotherapy beyond disease progression defined by the
      Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. METHODS: For
      this pooled analysis, we included all submissions of trial reports and data to
      the US Food and Drug Administration (FDA) in support of marketing applications
      for anti-programmed death receptor-1 (PD-1) antibodies (alone or in combination)
      for the treatment of patients with unresectable or metastatic melanoma that
      allowed for continuation of the antibody beyond RECIST-defined progression in the
      anti-PD-1 group and were approved by FDA before Jan 1, 2017. To investigate the
      effect of treatment beyond progression in patients with metastatic melanoma and
      to better characterise which of these patients would benefit from extended
      treatment, we pooled individual patient data from patients who received at least
      one dose of an anti-PD-1 antibody in the included trials. We included any patient
      receiving the anti-PD-1 antibody after their RECIST-defined progression date in
      the treatment beyond progression cohort and analysed them descriptively at
      baseline and at time of progression versus the cohort not receiving treatment
      beyond progression. We analysed the target lesion response after progression in
      patients in the treatment beyond progression cohort relative to progressive
      disease and baseline target lesion burden. We defined a treatment beyond
      progression response as a decrease in target lesion tumour burden (sum of the
      reference diameters) of at least 30% from the burden at the time of RECIST
      defined progression that did not require confirmation at a subsequent assessment.
      We also compared individual timepoint responses, overall survival, and adverse
      events in the treatment beyond progression versus no treatment beyond progression
      cohorts. FINDINGS: Among the eight multicentre clinical trials meeting this
      study's inclusion criteria, we pooled the data from 2624 patients receiving
      immunotherapy. 1361 (52%) had progressive disease, of whom 692 (51%) received
      continued anti-PD-1 antibody treatment beyond RECIST-defined progression and 669
      (49%) did not. 95 (19%) of 500 patients in the treatment beyond progresssion
      cohort with evaluable assessments had a 30% or more decrease in tumour burden,
      when considering burden at RECIST-defined progression as the reference point,
      representing 14% of the 692 patients treated beyond progression and 4% of all
      2624 patients treated with immunotherapy. Median overall survival in patients
      with RECIST-defined progressive disease given anti-PD-1 antibody was longer in
      the treatment beyond progression cohort (24.4 months, 95% CI 21.2-26.3) than in
      the cohort of patients who did not receive treatment beyond progression (11.2
      months, 10.1-12.9). 362 (54%) of 669 patients in the no treatment beyond
      progression cohort had a serious adverse event up to 90 days after treatment
      discontinuation compared with 295 (43%) of 692 patients in the treatment beyond
      progression cohort. Immune-related adverse events that occurred up to 90 days
      from discontinuation were similar between the treatment beyond progression cohort
      (78 [11%] of 692 patients) and the no treatment beyond progression cohort (106
      [16%] of 669). INTERPRETATION: Continuation of treatment beyond progression in
      the product labelling of these immunotherapies has not been recommended because
      the clinical benefit remains to be proven. Treatment beyond progression with anti
      PD-1 antibody therapy might be appropriate for selected patients with
      unresectable or metastatic melanoma, identified by specific criteria at the time
      of progression, based on the potential for late responses in the setting of the
      known toxicity profile. FUNDING: None.

PMID- 29361470
TI  - Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type
      recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept
      phase 2 study.
AB  - BACKGROUND: High-grade serous ovarian carcinoma is characterised by TP53
      mutations, DNA repair defects, and genomic instability. We hypothesised that
      prexasertib (LY2606368), a cell cycle checkpoint kinase 1 and 2 inhibitor, would
      be active in BRCA wild-type disease. METHODS: In an open-label, single-centre,
      two-stage, proof-of-concept phase 2 study, we enrolled women aged 18 years or
      older with measurable, recurrent high-grade serous or high-grade endometrioid
      ovarian carcinoma. All patients had a negative family history of hereditary
      breast and ovarian cancer or known BRCA wild-type status, measurable disease
      according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1,
      Eastern Cooperative Oncology Group performance status score 0-2, and adequate
      haematological, renal, hepatic, and bone-marrow function. Patients received
      intravenous prexasertib 105 mg/m2 administered over 1 h every 14 days in 28-day
      cycles until disease progression, unacceptable toxicity, or withdrawal of
      consent. The primary endpoint of investigator-assessed tumour response, based on
      RECIST version 1.1, was assessed per protocol (assessable patients who had
      undergone CT imaging at baseline and attended at least one protocol-specified
      follow-up) and by intention to treat. The final analysis of this cohort of
      patients with BRCA wild-type high-grade serous ovarian carcinoma is reported
      here. This ongoing trial is registered with ClinicalTrials.gov, number
      NCT02203513, and continues to enrol patients for the BRCA-mutated ovarian cancer
      cohort. FINDINGS: Between Jan 20, 2015, and Nov 2, 2016, we enrolled 28 women
      with a median age of 64 years (IQR 58.0-69.5) who had previously received a
      median of 5.0 (IQR 2.5-5.0) systemic therapies. Most patients (22 [79%]) had
      platinum-resistant or platinum-refractory disease. All women received at least
      one dose of prexasertib, but four (14%) of 28 patients were not assessable for
      RECIST response. Eight (33%, 95% CI 16-55) of 24 patients assessable per protocol
      had partial responses. In the intention-to-treat population, eight (29%, 95% CI
      13-49) of 28 had a partial responses. The most common (in >10% patients) grade 3
      or 4 treatment-emergent adverse events were neutropenia in 26 (93%) of 28
      patients, reduced white blood cell count in 23 (82%), thrombocytopenia in seven
      (25%), and anaemia in three (11%). Grade 4 neutropenia was reported in 22 (79%)
      patients after the first dose of prexasertib and was transient (median duration 6
      days [IQR 4-8]) and recovered without growth-factor support in all cases. The
      treatment-related serious adverse event of grade 3 febrile neutropenia was
      reported in two (7%) patients. One patient died during the study due to tumour
      progression. INTERPRETATION: Prexasertib showed clinical activity and was
      tolerable in patients with BRCA wild-type high-grade serous ovarian carcinoma.
      This drug warrants further development in this setting, especially for patients
      with platinum-resistant or platinum-refractory disease. FUNDING: Intramural
      Research Program of the National Institutes of Health and National Cancer
      Institute.

PMID- 29361472
TI  - Revisiting RECIST: the case of treatment beyond progression.

PMID- 29361473
TI  - Neoadjuvant therapy in melanoma: the next step?

PMID- 29361474
TI  - Microcytosis is important in screening of iron deficiency anemia.

PMID- 29361475
TI  - Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A
      nationwide study and systematic review.
AB  - INTRODUCTION: Recent years have seen major changes in clinical practice which may
      have affected the incidence rates of pheochromocytoma(PCC)/sympathetic
      paraganglioma(sPGL). There is, however, a lack of up-to-date information
      describing trends in these incidence rates. METHODS: We searched the Dutch
      pathology registry to identify all histopathologically confirmed cases of
      PCC/sPGL diagnosed between 1995 and 2015. We calculated incidence rates according
      to age category as well as age-standardized incidence rates (ASR). We also
      searched Medline and Embase to find data on nationwide incidence rates of
      PCC/sPGL. RESULTS: The nationwide pathology study revealed a total of 1493
      patients with either PCC or sPGL. The ASR for PCC increased from 0.29 (95% CI:
      0.24-0.33) to 0.46 (95% CI: 0.39-0.53) per 100,000 person-years in the periods
      1995-1999 and 2011-2015, respectively. For sPGL the ASR in these same periods
      were 0.08 (95% CI: 0.06-0.10) and 0.11 (95% CI: 0.09-0.13) per 100,000 person
      years, respectively. Concomitantly, PCC size decreased (beta -0.17; P < .001) and
      age at diagnosis increased (beta 0.13; P = .001). Our systematic search yielded 3
      papers reporting on a total of 530 PCC/sPGL cases, showing a combined annual
      incidence rate varying from 0.04 to 0.21 per 100,000 person-years. CONCLUSION:
      Incidence rates of PCC/sPGL have increased significantly over the past two
      decades. This trend coincides with a higher age and a smaller tumor size at
      diagnosis. Most likely these observations are at least in part the result of
      changes in clinical practice during the study period, with a more intensified use
      of both imaging studies and biochemical tests for detecting PCC/sPGL.

PMID- 29361477
TI  - Albumin-Binding MR Probe Detects High-Risk Coronary Plaques in Patients.

PMID- 29361476
TI  - Severe idiopathic pulmonary fibrosis: A clinical approach.
AB  - Idiopathic pulmonary fibrosis (IPF) is a devastating progressive disease
      associated with a high mortality rate. Novel antifibrotic therapies have been
      recently demonstrated to slow disease progression and improve survival. However,
      the management of IPF remains a difficult challenge, since lung complications can
      still occur, particularly in patients with advanced-stage disease. This paper
      highlights the most common complications and difficult tasks related to severe
      IPF such as acute exacerbation of the disease, development of lung cancer, rapid
      disease progression, and indication for lung transplantation.

PMID- 29361478
TI  - Targeted Imaging for Cell Death in Cardiovascular Disorders.
AB  - Cell death is desirable in cancer cells and undesirable in organs with limited
      regenerative potential, like the heart. Cell death comes in many forms, but only
      apoptosis and to a lesser degree necrosis is currently relevant to the clinical
      imager. Noninvasive imaging of cell death is an attractive option to understand
      pathophysiology, track disease activity, and evaluate response to intervention.
      Apoptosis seems to be the most promising target for imaging cell death, because
      it could be reversible and might be modulated with interventions. Molecular,
      nuclear, optical, or magnetic resonance imaging-based methods have been developed
      to identify intermediate steps in the apoptosis cascade. Animal studies show
      promising results for noninvasive imaging in various cardiovascular diseases.
      Human studies have shown feasibility, but clinical use is yet inconclusive. Newer
      technologies offer promise, especially for tracking apoptosis in evaluation of
      novel therapeutic interventions.

PMID- 29361481
TI  - nu-net: Deep Learning for Generalized Biventricular Mass and Function Parameters
      Using Multicenter Cardiac MRI Data.

PMID- 29361479
TI  - Feature-Tracking Global Longitudinal Strain Predicts Death in a Multicenter
      Population of Patients With Ischemic and Nonischemic Dilated Cardiomyopathy
      Incremental to Ejection Fraction and Late Gadolinium Enhancement.
AB  - OBJECTIVES: The aim of this study was to evaluate the prognostic value of cardiac
      magnetic resonance (CMR) feature-tracking-derived global longitudinal strain
      (GLS) in a large multicenter population of patients with ischemic and nonischemic
      dilated cardiomyopathy. BACKGROUND: Direct assessment of myocardial fiber
      deformation with GLS using echocardiography or CMR feature tracking has shown
      promise in providing prognostic information incremental to ejection fraction (EF)
      in single-center studies. Given the growing use of CMR for assessing persons with
      left ventricular (LV) dysfunction, we hypothesized that feature-tracking-derived
      GLS may provide independent prognostic information in a multicenter population of
      patients with ischemic and nonischemic dilated cardiomyopathy. METHODS:
      Consecutive patients at 4 U.S. medical centers undergoing CMR with EF <50% and
      ischemic or nonischemic dilated cardiomyopathy were included in this study.
      Feature-tracking GLS was calculated from 3 long-axis cine-views. The primary
      endpoint was all-cause death. Cox proportional hazards regression modeling was
      used to examine the association between GLS and death. Incremental prognostic
      value of GLS was assessed in nested models. RESULTS: Of the 1,012 patients in
      this study, 133 died during median follow-up of 4.4 years. By Kaplan-Meier
      analysis, the risk of death increased significantly with worsening GLS tertiles
      (log-rank p < 0.0001). Each 1% worsening in GLS was associated with an 89.1%
      increased risk of death after adjustment for clinical and imaging risk factors
      including EF and late gadolinium enhancement (LGE) (hazard ratio [HR]:1.891 per
      %; p < 0.001). Addition of GLS in this model resulted in significant improvement
      in the C-statistic (0.628 to 0.867; p < 0.0001). Continuous net reclassification
      improvement (NRI) was 1.148 (95% confidence interval: 0.996 to 1.318). GLS was
      independently associated with death after adjustment for clinical and imaging
      risk factors (including EF and late gadolinium enhancement) in both ischemic (HR:
      1.942 per %; p < 0.001) and nonischemic dilated cardiomyopathy subgroups (HR:
      2.101 per %; p < 0.001). CONCLUSIONS: CMR feature-tracking-derived GLS is a
      powerful independent predictor of mortality in a multicenter population of
      patients with ischemic or nonischemic dilated cardiomyopathy, incremental to
      common clinical and CMR risk factors including EF and LGE.

PMID- 29361480
TI  - Clinical Utility of Combined Optical Coherence Tomography and Near-Infrared
      Spectroscopy for Assessing the Mechanism of Very Late Stent Thrombosis.

PMID- 29361482
TI  - Poor Correlation, Reproducibility, and Agreement Between Volumetric Versus Linear
      Epicardial Adipose Tissue Measurement: A 3D Computed Tomography Versus 2D
      Echocardiography Comparison.

PMID- 29361483
TI  - Atherosclerosis, Stenosis, and Ischemia: One Primary, One Secondary, and One
      Tertiary.

PMID- 29361484
TI  - Same Lesion, Different Artery, Different FFR!?

PMID- 29361485
TI  - LBBB and High Afterload: A Dangerous Liaison?

PMID- 29361486
TI  - Afterload Hypersensitivity in Patients With Left Bundle Branch Block.
AB  - OBJECTIVES: This study sought to investigate the hypothesis that patients with
      left bundle branch block (LBBB) are hypersensitive to elevated afterload.
      BACKGROUND: Epidemiological data suggest that LBBB can provoke heart failure in
      patients with hypertension. METHODS: In 11 asymptomatic patients with isolated
      LBBB and 11 age-matched control subjects, left ventricular ejection fraction
      (LVEF) and global longitudinal strain (GLS) were measured by echocardiography.
      Systolic arterial pressure was increased by combining pneumatic extremity
      constrictors and handgrip exercise. To obtain more insight into mechanisms of
      afterload response, 8 anesthetized dogs with left ventricular (LV) micromanometer
      and dimension crystals were studied during acutely induced LBBB and aortic
      constriction. Regional myocardial work was assessed by LV pressure-dimension
      analysis. RESULTS: Consistent with normal afterload dependency, elevation of
      systolic arterial pressure by 38 +/- 12 mm Hg moderately reduced LVEF from 60 +/-
      4% to 54 +/- 6% (p < 0.01) in control subjects. In LBBB patients, however, a
      similar blood pressure increase caused substantially larger reduction in LVEF (p
      < 0.01), from 56 +/- 6% to 42 +/- 7% (p < 0.01). There were similar findings for
      GLS. In the dog model, aortic constriction abolished septal shortening (p <
      0.02), and septal work decreased to negative values (p < 0.01). Therefore, during
      elevated systolic pressure, the septum made no contribution to global LV work, as
      indicated by net negative work, and instead absorbed energy from work done by the
      LV lateral wall. CONCLUSIONS: Moderate elevation of arterial pressure caused
      marked reductions in LVEF and GLS in patients with LBBB. This reflects a
      cardiodepressive effect of elevated afterload in the dyssynchronous ventricle and
      was attributed to loss of septal function.

PMID- 29361487
TI  - Novel Approach for In Vivo Detection of Vulnerable Coronary Plaques using
      Molecular 3-T CMR Imaging with an Albumin-Binding Probe.
AB  - OBJECTIVES: This study sought to investigate the potential of the noninvasive
      albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR)
      for detection of coronary plaques that can cause acute coronary syndromes (ACS).
      BACKGROUND: ACS are frequently caused by rupture or erosion of coronary plaques
      that initially do not cause hemodynamically significant stenosis and are
      therefore not detected by invasive x-ray coronary angiography (XCA). METHODS: A
      total of 25 patients with ACS or symptoms of stable coronary artery disease
      underwent GE-CMR, clinically indicated XCA, and optical coherence tomography
      (OCT) within 24 h. GE-CMR was performed approximately 24 h following a 1-time
      application of gadofosveset-trisodium. Contrast-to-noise ratio (CNR) was
      quantified within coronary segments in comparison with blood signal. RESULTS: A
      total of 207 coronary segments were analyzed on GE-CMR. Segments containing a
      culprit lesion in ACS patients (n = 11) showed significant higher signal
      enhancement (CNR) following gadofosveset-trisodium application than segments
      without culprit lesions (n = 196; 6.1 [3.9 to 16.5] vs. 2.1 [0.5 to 3.5]; p <
      0.001). GE-CMR was able to correctly identify culprit coronary lesions in 9 of 11
      segments (sensitivity 82%) and correctly excluded culprit coronary lesions in 162
      of 195 segments (specificity 83%). Additionally, segmented areas of thin-cap
      fibroatheroma (n = 22) as seen on OCT demonstrated significantly higher CNR than
      segments without coronary plaque or segments containing early atherosclerotic
      lesions (n = 185; 9.2 [3.3 to 13.7] vs. 2.1 [0.5 to 3.4]; p = 0.001).
      CONCLUSIONS: In this study, we demonstrated for the first time the noninvasive
      detection of culprit coronary lesions and thin-cap fibroatheroma of the coronary
      arteries in vivo by using GE-CMR. This method may represent a novel approach for
      noninvasive cardiovascular risk prediction.

PMID- 29361488
TI  - Regional Left Ventricular Myocardial Mechanics in Degenerative Myxomatous Mitral
      Valve Disease: A Comparison Between Fibroelastic Deficiency and Barlow's Disease.

PMID- 29361489
TI  - Liver Stiffness Reflecting Right-Sided Filling Pressure Can Predict Adverse
      Outcomes in Patients With Heart Failure.
AB  - OBJECTIVES: This study sought to investigate whether elevated liver stiffness
      (LS) values at discharge reflect residual liver congestion and are associated
      with worse outcomes in patients with heart failure (HF). BACKGROUND: Transient
      elastography is a newly developed, noninvasive method for assessing LS, which can
      be highly reflective of right-sided filling pressure associated with passive
      liver congestion in patients with HF. METHODS: LS values were determined for 171
      hospitalized patients with HF before discharge using a Fibroscan device. RESULTS:
      The median LS value was 5.6 kPa (interquartile range: 4.4 to 8.1; range 2.4 to
      39.7) and that of right-sided filling pressure, which was estimated based on LS,
      was 5.7 mm Hg (interquartile range: 4.1 to 8.2 mm Hg; range 0.1 to 18.9 mm Hg).
      The patients in the highest LS tertile (>6.9 kPa, corresponding to an estimated
      right-sided filling pressure of >7.1 mm Hg) had advanced New York Heart
      Association functional class, high prevalence of jugular venous distention and
      moderate/severe tricuspid regurgitation, large inferior vena cava (IVC) diameter,
      low hemoglobin and hematocrit levels, high serum direct bilirubin level, and a
      similar left ventricular ejection fraction compared with the lower tertiles.
      During follow-up periods (median: 203 days), 8 (5%) deaths and 33 (19%)
      hospitalizations for HF were observed. The patients in the highest LS group had a
      significantly higher mortality rate and HF rehospitalization (hazard ratio: 3.57;
      95% confidence interval: 1.93 to 6.83; p < 0.001) compared with the other
      tertiles. Although LS correlated with IVC diameter and serum direct bilirubin and
      brain natriuretic peptide levels, LS values were predictive of worse outcomes,
      even after adjustment for these indices. CONCLUSIONS: These data suggest that LS
      is a useful index for assessing systemic volume status and predicting the
      severity of HF, and that the presence of liver congestion at discharge is
      associated with worse outcomes in patients with HF.

PMID- 29361490
TI  - Deranged Myocyte Microstructure in Situs Inversus Totalis Demonstrated by
      Diffusion Tensor Cardiac Magnetic Resonance.

PMID- 29361491
TI  - Incremental Value of Subtended Myocardial Mass for Identifying FFR-Verified
      Ischemia Using Quantitative CT Angiography: Comparison With Quantitative Coronary
      Angiography and CT-FFR.
AB  - OBJECTIVES: This study examined the incremental value of subtended myocardial
      mass (Vsub) as assessed by coronary computed tomography angiography (CTA) for
      identifying lesion-specific ischemia verified by invasive fractional flow reserve
      (FFR) in quantitative coronary CTA. BACKGROUND: FFR is determined not only by
      coronary stenosis severity, but also by Vsub. One-step evaluation of combined
      Vsub and coronary lesion morphology may improve the accuracy of coronary CTA for
      identifying ischemia-producing lesions. METHODS: A total of 246 intermediate
      coronary artery lesions (30% to 80% diameter stenosis) in 220 patients (mean age
      61.7 years, 168 men) interrogated by FFR were retrospectively studied. Coronary
      CTA data were used to assess the Vsub by coronary artery stenosis, minimal lumen
      area (MLA), percentage of aggregated plaque volume (%APV), positive remodeling,
      and low-attenuation plaque. The ability of Vsub/MLA2 to discriminate lesions with
      FFR <=0.80 was examined. Diagnostic performance, odds ratios, and category-less
      net reclassification improvements of coronary CTA parameters for FFR-verified
      (<=0.80) ischemia were evaluated. On-site computed tomography (CT) derived-FFR
      (CT-FFR) and quantitative coronary angiography (QCA) data were also compared.
      RESULTS: Of 246 lesions, 84 (34.1%) showed an FFR <=0.80. Vsub was independently
      associated with an FFR <=0.80 (odds ratio: 1.04/1 cm3; p = 0.032) and showed
      incremental value over MLA. Vsub/MLA2 >4.16 was the best single parameter for
      discriminating an FFR <=0.80 with 83.3% sensitivity and 67.9% specificity. The
      area under the curve (AUC) of Vsub/MLA2 >4.16 (0.80 [95% confidence interval:
      0.75 to 0.85]) was better than that of MLA (change in [Delta]AUC: 0.069; p <
      0.001), %APV (DeltaAUC: 0.096; p = 0.017), and diameter stenosis of QCA
      (DeltaAUC: 0.080; p = 0.037) and was comparable to that of CT-FFR (AUC 0.77;
      DeltaAUC: 0.035; p = 0.304). CONCLUSIONS: Vsub is an independent determinant of
      an FFR <=0.80. The mathematical index of Vsub/MLA2 >4.16 assessed by coronary CTA
      shows better diagnostic performance for the detection of ischemia-producing
      lesions than CT-derived MLA alone or %APV and QCA parameters and was comparable
      to that of on-site CT-FFR.

PMID- 29361494
TI  - Stone Liver, Heart in Danger: Could the Liver Stiffness Assessment Improve the
      Management of Patients With Heart Failure?

PMID- 29361493
TI  - Many Faces of Fabry's Cardiomyopathy.

PMID- 29361492
TI  - Intra-Atrial Dyssynchrony During Sinus Rhythm Predicts Recurrence After the First
      Catheter Ablation for Atrial Fibrillation.
AB  - OBJECTIVES: The purpose of this study was to evaluate the usefulness of intra
      atrial dyssynchrony as a marker of underlying left atrial (LA) remodeling to
      predict recurrence after the first atrial fibrillation (AF) ablation. BACKGROUND:
      Catheter ablation for AF remains far from curative with relatively high
      recurrence rates. One of the causes of recurrence is poor patient selection out
      of a diverse patient population with different degrees of LA remodeling. METHODS:
      We included 208 patients with a history of AF (59.4 +/- 10 years of age; 26.0%
      nonparoxysmal AF) referred for catheter ablation of AF who underwent pre-ablation
      cardiac magnetic resonance in sinus rhythm. Clinical follow-up was 20 +/- 6
      months. Using tissue tracking cardiac magnetic resonance, we measured the LA
      longitudinal strain in each of 12 equal-length segments in 2- and 4-chamber
      views. We defined intra-atrial dyssynchrony as the standard deviation of the time
      to the peak longitudinal strain corrected by the cycle length (SD-time to peak
      strain [TPS], %). RESULTS: Patients with AF recurrence after ablation (n = 101)
      had significantly higher SD-TPS than those without (n = 107; 3.9% vs. 2.2%; p <
      0.001). Multivariable cox analysis showed that SD-TPS was associated with
      recurrence after adjusting for clinical risk factors, AF type, LA structure and
      function, and fibrosis (p < 0.001). Furthermore, receiver-operator
      characteristics analysis showed SD-TPS improved prediction of recurrence better
      than clinical risk factors, LA structure and function, and fibrosis. CONCLUSIONS:
      Intra-atrial dyssynchrony during sinus rhythm is an independent predictor of
      recurrence after the first catheter ablation of paroxysmal or persistent AF.
      Assessment of intra-atrial dyssynchrony may improve ablation outcomes by refining
      patient selection.

PMID- 29361495
TI  - Mechanisms of Hypercalcemia in Non-Hodgkin Lymphoma and Associated Outcomes: A
      Retrospective Review.
AB  - INTRODUCTION: The etiology of hypercalcemia in non-Hodgkin lymphoma (NHL) has
      been most often attributed to either elevated serum levels of 1,25
      dihydroxycholecalciferol (calcitriol) or parathyroid-related protein (PTHrP). In
      a single-center retrospective review, we evaluated the incidence of, and outcomes
      associated with, hypercalcemia in NHL. PATIENTS AND METHODS: The medical records
      of patients with a histologically confirmed diagnosis of NHL and >= 1 episode of
      hypercalcemia were evaluated for demographic and lymphoma-specific factors,
      including the response to therapy and overall survival. RESULTS: Fifty-four
      patients with NHL met the inclusion criteria. Most patients (57.4%) had diffuse
      large B-cell lymphoma, of which, 70% were the nongerminal center subtype.
      Approximately one half (42.6%) of the included patients had undergone serologic
      investigation into the etiology of hypercalcemia; however, only 17 patients
      (31.5%) had both a serum PTHrP and a calcitriol level properly collected. Of the
      17 cases for which both a serum calcitriol and a PTHrP were collected, most
      (61.1%) were found to have neither an elevation of serum calcitriol nor an
      elevation of PTHrP. The degree of calcitriol elevation correlated with worse
      progression-free survival (P = .04) but not overall survival. CONCLUSION: The
      major mechanism by which NHL patients develop hypercalcemia is not mediated by
      calcitriol or PTHrP. Hypercalcemia is most prevalent in patients with diffuse
      large B-cell lymphoma of the nongerminal cell subtype. Patients with calcitriol
      mediated hypercalcemia showed a trend toward worse outcomes, suggesting that
      calcitriol might be a marker of high-grade lymphoma, transformation to such, or a
      surrogate for more advanced disease.

PMID- 29361496
TI  - Associations of lipoproteins with cardiovascular and infection-related outcomes
      in patients receiving hemodialysis.
AB  - BACKGROUND: In hemodialysis (HD) patients, higher lipid levels are associated
      with lower mortality. Lipid-lowering therapy does not reduce all-cause mortality
      or cardiovascular (CV) mortality. Lipoproteins play a role in the innate immune
      system. Our objective was to determine whether protection from infection might
      counterbalance adverse CV outcomes associated with lipoproteins. METHODS: We
      examined associations between serum apolipoprotein (Apo) A1, B, C2, C3, high
      density lipoprotein and low-density lipoprotein (LDL) cholesterol and
      triglyceride levels and infectious mortality or hospitalization, CV mortality or
      hospitalization, and all-cause mortality in 433 prevalent HD patients. Cox models
      with time-varying apolipoprotein concentrations collected every 6 months for up
      to 2 years were used for analyses. RESULTS: Median follow-up time for all-cause
      mortality was 2.7 years (25th-75th percentile range: 2.2-3.4 years). One hundred
      seventy-nine (41%) patients had an infection-related event. In multivariable
      models, higher Apo B and LDL were associated with lower risks of infection
      related outcomes (hazard ratio Apo B 0.92 [95% confidence interval 0.86-0.99 per
      10 mg/dL, P = .03]; hazard ratio LDL 0.93 [95% confidence interval 0.87-1.00 per
      10 mg/dL, P = .05]). Sixty-three (15%) participants had a CV-related event. No
      significant associations were observed between lipoproteins and CV outcomes.
      Eighty-seven (20%) participants died. Higher Apo A1, Apo B, and Apo C3 were
      associated with lower risks of all-cause mortality. There was no interaction
      between the use of lipid-lowering medication and any of the outcomes. CONCLUSION:
      Associations of lipoproteins with lower risk of serious infection accompanied by
      no significant association with CV events may help to explain the paradoxical
      association between lipids and survival and lack of benefit of lipid-lowering
      therapies in HD.

PMID- 29361497
TI  - Reversal of metabolic disorders by pharmacological activation of bile acid
      receptors TGR5 and FXR.
AB  - OBJECTIVES: Activation of the bile acid (BA) receptors farnesoid X receptor (FXR)
      or G protein-coupled bile acid receptor (GPBAR1; TGR5) improves metabolic
      homeostasis. In this study, we aim to determine the impact of pharmacological
      activation of bile acid receptors by INT-767 on reversal of diet-induced
      metabolic disorders, and the relative contribution of FXR vs. TGR5 to INT-767's
      effects on metabolic parameters. METHODS: Wild-type (WT), Tgr5-/-, Fxr-/-, Apoe-/
      and Shp-/- mice were used to investigate whether and how BA receptor activation
      by INT-767, a semisynthetic agonist for both FXR and TGR5, could reverse diet
      induced metabolic disorders. RESULTS: INT-767 reversed HFD-induced obesity
      dependent on activation of both TGR5 and FXR and also reversed the development of
      atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Mechanistically,
      INT-767 improved hypercholesterolemia by activation of FXR and induced
      thermogenic genes via activation of TGR5 and/or FXR. Furthermore, INT-767
      inhibited several lipogenic genes and de novo lipogenesis in the liver via
      activation of FXR. We identified peroxisome proliferation-activated receptor
      gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (CEBPalpha) as novel
      FXR-regulated genes. FXR inhibited PPARgamma expression by inducing small
      heterodimer partner (SHP) whereas the inhibition of CEBPalpha by FXR was SHP
      independent. CONCLUSIONS: BA receptor activation can reverse obesity, NAFLD, and
      atherosclerosis by specific activation of FXR or TGR5. Our data suggest that,
      compared to activation of FXR or TGR5 only, dual activation of both FXR and TGR5
      is a more attractive strategy for treatment of common metabolic disorders.

PMID- 29361498
TI  - Respiromics - An integrative analysis linking mitochondrial bioenergetics to
      molecular signatures.
AB  - OBJECTIVE: Energy metabolism is challenged upon nutrient stress, eventually
      leading to a variety of metabolic diseases that represent a major global health
      burden. METHODS: Here, we combine quantitative mitochondrial respirometry
      (Seahorse technology) and proteomics (LC-MS/MS-based total protein approach) to
      understand how molecular changes translate to changes in mitochondrial energy
      transduction during diet-induced obesity (DIO) in the liver. RESULTS: The
      integrative analysis reveals that significantly increased palmitoyl-carnitine
      respiration is supported by an array of proteins enriching lipid metabolism
      pathways. Upstream of the respiratory chain, the increased capacity for ATP
      synthesis during DIO associates strongest to mitochondrial uptake of pyruvate,
      which is routed towards carboxylation. At the respiratory chain, robust increases
      of complex I are uncovered by cumulative analysis of single subunit
      concentrations. Specifically, nuclear-encoded accessory subunits, but not
      mitochondrial-encoded or core units, appear to be permissive for enhanced lipid
      oxidation. CONCLUSION: Our integrative analysis, that we dubbed "respiromics",
      represents an effective tool to link molecular changes to functional mechanisms
      in liver energy metabolism, and, more generally, can be applied for mitochondrial
      analysis in a variety of metabolic and mitochondrial disease models.

PMID- 29361499
TI  - A Brief History of Coronary Artery Stents.

PMID- 29361500
TI  - Long-term Persistent Elite HIV-controllers: The Right Model of Functional Cure.

PMID- 29361502
TI  - Dentures wearing reduce motion artifacts related to tongue movement in magnetic
      resonance imaging.
AB  - PURPOSE: Tongue movement with unstable swallowing cause artifacts on magnetic
      resonance imaging (MRI). This may be associated with loss of occlusal support.
      This study aimed to clarify whether motion artifacts can be mitigated by denture
      wearing during MRI examination in patients without occlusal support, and whether
      denture wearing affect tongue stability, form, and position were also evaluated.
      METHODS: Ten subjects without occlusal support (6 male, 4 female; mean age
      73.20+/-10.12 years) participated in the study. MRI was performed with dentures
      worn (DW), followed with removal of dentures (NDW). Luminance standard deviation
      (LSD) was measured in regions of interest in the axial and sagittal planes. The
      position of the base of the tongue (TB), tip of the tongue apex (TA), and
      tongue's long diameter (TLD) were compared between DW and NDW. RESULTS: NDW
      evoked ambiguous MR images in the axial and sagittal planes compared with DW.
      There were significant differences in LSD between DW and NDW in both the axial
      (p=0.047) and sagittal planes (p=0.02). No significant difference in the position
      of TB were observed (p=0.78). The position of TA was significantly more protruded
      with DW (p=0.007). Also, TLD was significantly longer with DW (p=0.001).
      CONCLUSIONS: Results of this study suggest that wearing the dentures during MRI
      examination reduces motion artifacts in edentulous patients without occlusal
      support, and maintained the normal form of the tongue during imaging.

PMID- 29361501
TI  - Synthetic High-Density Lipoprotein-Mediated Targeted Delivery of Liver X
      Receptors Agonist Promotes Atherosclerosis Regression.
AB  - Targeting at enhancing reverse cholesterol transport (RCT) is apromising strategy
      for treating atherosclerosis via infusion of reconstitute high density
      lipoprotein (HDL) as cholesterol acceptors or increase of cholesterol efflux by
      activation of macrophage liver X receptors (LXRs). However, systemic activation
      of LXRs triggers excessive lipogenesis in the liver and infusion of HDL
      downregulates cholesterol efflux from macrophages. Here we describe an
      enlightened strategy using phospholipid reconstituted apoA-I peptide (22A)
      derived synthetic HDL (sHDL) to deliver LXR agonists to the atheroma and examine
      their effect on atherosclerosis regression in vivo. A synthetic LXR agonist,
      T0901317 (T1317) was encapsulated in sHDL nanoparticles (sHDL-T1317). Similar to
      the T1317 compound, the sHDL-T1317 nanoparticles upregulated the expression of
      ATP-binding cassette transporters and increased cholesterol efflux in macrophages
      in vitro and in vivo. The sHDL nanoparticles accumulated in the atherosclerotic
      plaques of ApoE-deficient mice. Moreover, a 6-week low-dose LXR agonist-sHDL
      treatment induced atherosclerosis regression while avoiding lipid accumulation in
      the liver. These findings identify LXR agonist loaded sHDL nanoparticles as a
      promising therapeutic approach to treat atherosclerosis by targeting RCT in a
      multifaceted manner: sHDL itself serving as both a drug carrier and cholesterol
      acceptor and the LXR agonist mediating upregulation of ABC transporters in the
      aorta.

PMID- 29361504
TI  - The development and evaluation of a novel repurposing of a peripheral gaming
      device for the acquisition of forces applied to a hydraulic treatment plinth.
AB  - This technical note details the stages taken to create an instrumented hydraulic
      treatment plinth for the measurement of applied forces in the vertical axis. The
      modification used a widely available low-cost peripheral gaming device and
      required only basic construction and computer skills. The instrumented treatment
      plinth was validated against a laboratory grade force platform across a range of
      applied masses from 0.5-15 kg, mock Gr I-IV vertebral mobilisations and a dynamic
      response test. Intraclass correlation coefficients demonstrated poor reliability
      (0.46) for low masses of 0.5 kg improving to excellent for larger masses up to15
      kg respectively; excellent to good reliability (0.97-0.86) for the mock
      mobilisations and moderate reliability (0.51) for the dynamic response test. The
      study demonstrates how a cheap peripheral gaming device can be repurposed so that
      forces applied to a hydraulic treatment plinth can be collected reliably when
      applied in a clinically reasoned manner.

PMID- 29361503
TI  - Twin studies for the prognosis, prevention and treatment of musculoskeletal
      conditions.
AB  - BACKGROUND: Musculoskeletal conditions are highly prevalent in our ageing society
      and are therefore incurring substantial increases in population levels of years
      lived with disability (YLD). An evidence-based approach to the prognosis,
      prevention, and treatment of those disorders can allow an overall improvement in
      the quality of life of patients, while also softening the burden on national
      health care systems. METHODS: In this Masterclass article, we provide an overview
      of the most relevant twin study designs, their advantages, limitations and major
      contributions to the investigation of traits related to the domain of
      musculoskeletal physical therapy. CONCLUSIONS: Twin studies can be an important
      scientific tool to address issues related to musculoskeletal conditions. They
      allow researchers to understand how genes and environment combine to influence
      human health and disease. Twin registries and international collaboration through
      existing networks can provide resources for achieving large sample sizes and
      access to expertise in study design and analysis of twin data.

PMID- 29361506
TI  - Supplementing Resident Research Funding Through a Partnership With Local
      Industry.
AB  - OBJECTIVE: To develop a model for the supplementation of resident research
      funding through a resident-hosted clinical immersion with local industry. DESIGN:
      Designated research residents hosted multiple groups of engineers and business
      professionals from local industry in general surgery-focused clinical immersion
      weeks. The participants in these week-long programs are educated about general
      surgery and brought to the operating room to observe a variety of surgeries.
      SETTING: This study was performed at the University of Minnesota, in Minneapolis,
      Minnesota, at a tertiary medical center. PARTICIPANTS: Ten designated research
      residents hosted general surgery immersion programs. Fifty-seven engineers and
      business professionals from 5 different local biomedical firms have participated
      in this program. RESULTS: General surgery research residents (in collaboration
      with the University of Minnesota's Institute for Engineering in Medicine) have
      hosted 9 clinical immersion programs since starting the collaborative in 2015.
      Immersion participant response to the experiences was very positive. Two full
      time resident research positions can be funded annually through participation in
      this program. CONCLUSIONS: With decreasing funding available for surgical
      research, particularly resident research, innovative ways to fund resident
      research are needed. The general surgery clinical immersion program at the
      University of Minnesota has proven its value as a supplement for resident
      research funding and may be a sustainable model for the future.

PMID- 29361505
TI  - A bibiliometric analysis of the Journal of Infection and Public Health: 2008
      2016.
AB  - BACKGROUND: The Journal of Infection and Public Health published its first issue
      in 2008. The fact that the journal has been published uninterruptedly as well as
      its editorial content and the application of a peer-review process to select
      manuscripts, made the journal eligible to be indexed by databases such as Scopus.
      This study presents a general overview of the journal from 2008 until 2016 using
      bibliometric indicators to assess its performance. METHODS: The data for this
      study, dating between 2008 and 2016, was extracted from Scopus database. All the
      information was exported in CSV format to the Sequel Pro software for data
      analysis. Additionally, collaboration and word co-occurrence networks were
      generated using VOSviewer. RESULTS: The total number of documents published
      between 2008-2016 was 586, of which local authorship (Saudi Arabia) constituted a
      small share, accounting only for 19.3% (113 documents). Those with foreign
      authorship (other countries excluding Saudi Arabia) represented 80.7% (473) of
      the total. Furthermore, the three countries that co-author documents with
      researchers from Saudi Arabia are Egypt, the United States and the United
      Kingdom. Likewise, these three countries serve as nodes connecting researchers
      from other countries located in Asia, Africa, Europe and Latin America. An
      analysis of the top-five journals that cited the research published revealed that
      that 90.2% of them belonged to the first and second quartiles confirms the
      quality of the research being published. Word co-occurrence analysis established
      a slight shift of focus in the research topics published during the last four
      years studied, as a new cluster was formed with terms related to "education",
      "intervention" and "implementation". CONCLUSION: The journal has managed, in very
      few years, to be considered by researchers worldwide. Furthermore, throughout the
      years, the journal showed an evolution in the main topics covered, providing a
      contemporary overview of public health.

PMID- 29361507
TI  - Dr. Congeniality: Understanding the Importance of Surgeons' Nontechnical Skills
      Through 360 degrees  Feedback.
AB  - OBJECTIVE: Physician performance is a complex construct that is broadly defined
      by technical and nontechnical components. The primary aim of this study was to
      identify which Big Five personality traits (openness, conscientiousness,
      extraversion, agreeableness, and emotional stability) in surgeons were related to
      patient satisfaction and teamwork performance in a surgical setting. A secondary
      aim of this study was to examine the specific perceptions of physician behavior
      related to patient satisfaction and teamwork performance. DESIGN: Orthopedic
      surgeons received anonymous multisource 360 degrees  feedback from managers,
      colleagues, nurses, technicians, and trainees. Personality traits were
      categorized with a modified Delphi Consensus technique using the Big Five
      framework. Patient satisfaction was measured using retrospective Clinician &
      Group-Consumer Assessment of Healthcare Providers and System (CG-CAHPS) data.
      Teamwork performance was measured using the Quality PULSE 360 Teamwork Index.
      SETTING: Research was performed at a large academic medical center in the
      northeastern United States. PARTICIPANTS: Participants in this study included a
      sample of 24 orthopedic surgeons. RESULTS: Backward stepwise regressions were
      used to determine which model with the most variance used the fewest explanatory
      variables. Personality traits acted as predictor variables in the regression
      models and patient satisfaction and teamwork performance were utilized as outcome
      variables. The higher the physicians' emotional stability, the higher patients'
      overall satisfaction (beta = 0.41, p = 0.04) and willingness to recommend them to
      other patients (beta = 0.45, p = 0.03). Furthermore, high emotional stability was
      related to effective surgical teams as rated by team members (beta = -0.75, p =
      0.00) such that the more emotionally stable physicians were, the higher their
      teamwork rating by colleagues. CONCLUSIONS: Both physicians-in-training and in
      practice physicians may benefit from engaging in empathic and constructive
      behaviors with patients and team members.

PMID- 29361508
TI  - Building a Simulator with Life-like Realism for Teaching Abdominal Operations.
AB  - OBJECTIVE: The objective of this communication is to provide an evolutionary
      description of an attempt to replicate the success of the Rampahl Cardiac
      Simulator using perfused abdominal organ blocks the way that the Rampahl
      Simulator uses ex vivo porcine hearts. DESIGN: This descriptive paper makes no
      attempt to prove the effectiveness of the described educational tool, but rather,
      outlines the successes and failures in development. The proven value of a
      perfused organ teaching tool, as the Rampahl Simulator, suggests that others can
      build upon the work described in this paper so that, in the future, perfused
      abdominal organs will be available to students of general surgery as a routine
      part of their pre-operative preparation. SETTING: The Animal Resource Facility of
      the University of Utah, under the oversight of the University Institutional
      Animal Use and Care Committee (IACUC), provided the animals, operating suites and
      technical support. PARTICIPANTS: During each development phase, General Surgery
      Residents and Medical Students from all levels participated. In addition,
      operating room staff with an interest in either medical school or perfusion were
      invited to participate. RESULTS: The efforts described in this paper eventually
      resulted in a reliable teaching tool for abdominal procedures in that viability
      of the porcine abdominal organs for up to three hours after euthanasia was
      regularly achieved. CONCLUSIONS: General Surgery Teaching Programs of a size
      similar to the University of Utah may have access to the resources necessary to
      replicate this teaching tool in a cost-effective manner. However smaller teaching
      programs, such as those without a research facility, may not be able to adapt the
      procedures described in this paper.

PMID- 29361509
TI  - Renal Transplantation as a Platform for Teaching Residents Open Vascular Surgical
      Techniques: Effects on Early Graft Function.
AB  - BACKGROUND: Over the past decade, increases in vascular fellowships and the use
      of endovascular technology have decreased the general surgery residents' exposure
      to open vascular surgery. We sought to elucidate whether renal transplant is a
      safe way to teach general surgery residents the essential tenants of vascular
      surgery without adversely affecting early patient outcomes. METHODS: All
      solitary, adult deceased donor kidney transplants performed at the University of
      Wisconsin from 2011 through 2016 were identified and divided into a resident
      assist (RA) and fellow-assist cohorts (FA). DGF, defined by the requirement of
      dialysis within 1 week of transplant, was the primary outcome. Early graft
      survival and postoperative complications were considered the secondary endpoints.
      RESULTS: Of the 774 total cases, there were 228 (29.5%) in the RA cohort and 546
      (70.5%) in the FA cohort. The RA and FA cohorts had comparable characteristics,
      except for a nonclinically significant difference in mean donor creatinine (0.96
      vs 0.88mg/dL, p = 0.03). RA cases had a similar DGF rate compared to FA cases
      (25% vs 26%, p = 0.93). Additionally, there was no difference in 2-year graft
      survival (93.7% vs 95.5%, p = 0.38), nor the rates of graft thromboses (0.4% vs
      0.7%, p = 0.65), incisional hernias (0.9% vs 1.8%, p = 0.35), and ureteral
      strictures (2.2% vs 1.6%, p = 0.55) between the 2 cohorts. CONCLUSIONS: Resident
      involvement in renal transplantation has no effect on DGF and early allograft
      function. Though the procedural involvement of each resident in a case is
      variable, it seems to be a safe way to teach retroperitoneal vascular exposure
      and anastomotic techniques.

PMID- 29361510
TI  - Asthma and Allergic Disorders in Uganda: A Population-Based Study Across Urban
      and Rural Settings.
AB  - BACKGROUND: Allergic diseases are increasing in sub-Saharan Africa, but few
      studies have characterized the burden among adults. OBJECTIVE: We conducted a
      study to evaluate the prevalence and risk factors of allergic disorders in urban
      and rural Uganda. METHODS: We present a cross-sectional analysis of enrollment
      data from a population-based cohort study of adults aged >=35 years in urban and
      rural Uganda. Sociodemographic and both lifetime and 12-month respiratory
      symptoms data were collected and spirometry was conducted following standard
      guidelines. RESULTS: In 1,308 adults (median age 43.8 years and 52.3% female), we
      found an age-adjusted prevalence of 6.8% for asthma (9.8% urban, 4.3% rural; P <
      .001), 11.9% for allergic rhinitis (16.4% urban, 7.8% rural; P < .001), and 8.2%
      for eczema (9.9% urban, 7.8% rural; P = .15). Urbanization was the primary driver
      of asthma, accounting for 61.4% of cases (95% confidence interval [CI] 22.0% to
      83.4%), and was the strongest risk factor for any allergic illness (odds ratio
      [OR] = 1.87, 95% CI 1.39-2.51). Parental asthma was not associated with allergic
      illness. Asthma was associated with a lower forced expiratory volume in 1 second
      (FEV1) by 0.56 z scores (95% CI 0.33-0.80). We found a dose-response association
      between lower quintiles of the FEV1/forced vital capacity ratio and both
      hospitalization (OR = 1.77, 95% CI 1.21-2.59) and impairment in daily activities
      (1.65, 1.20-2.27). CONCLUSIONS: Asthma and allergic rhinitis were twice as
      prevalent in urban settings. Asthma was associated with greater impairment and
      worse lung function outcomes. We identified a high prevalence of allergic
      disorders in Uganda, which can be expected to increase due to urbanization and
      resultant exposures throughout early development.

PMID- 29361511
TI  - Outcome of 490 Desensitizations to Chemotherapy Drugs with a Rapid One-Solution
      Protocol.
AB  - BACKGROUND: Hypersensitivity reactions to chemotherapy drugs are quite frequent.
      Desensitization for chemotherapy drugs has become an option to maintain first
      line therapy in patients who have suffered such reactions. OBJECTIVE: The
      objective of this study was to describe our experience in desensitization with
      antineoplastic agents using a rapid 1-solution protocol. METHODS: We performed a
      3-year prospective observational study recording all patients who were
      desensitized with this protocol. All patients signed an informed consent. Skin
      test was performed at concentrations previously described as nonirritant.
      Desensitization was performed using only 1 solution of the drug prepared
      following the manufacturer instructions. Most drugs were diluted in a volume of
      500 mL. We started infusion at 5 mL/h and increased doses at 15-minute intervals
      to 10, 25, 50, 75, and 100 mL/h. If no reaction occurred, and if the
      pharmacokinetics of the drug allowed it, we stepped up to 150, 200, and 250 mL/h.
      RESULTS: Ninety patients were desensitized to 93 drugs: oxaliplatin (30),
      carboplatin (16), paclitaxel (19), docetaxel (6), cetuximab (5), rituximab (6),
      and others (11). A total number of 490 procedures were performed. Sixteen
      patients (17.77%) presented 26 reactions (5.3%). Most reactions appeared in
      patients who were desensitized to platins and in patients with severe reactions.
      All but 3 cycles were completely administrated. No deaths or hospital admissions
      were recorded. CONCLUSIONS: This 1-solution protocol for desensitization has
      demonstrated to be safe and useful in our study population, especially for mild
      to-moderate reactions and nonplatinum drugs. If our results were reproducible in
      other centers and larger populations, they could contribute to simplifying
      protocols and making desensitization available for more patients.

PMID- 29361512
TI  - Environmental factors regulate Paneth cell phenotype and host susceptibility to
      intestinal inflammation in Irgm1-deficient mice.
AB  - Crohn's disease (CD) represents a chronic inflammatory disorder of the intestinal
      tract. Several susceptibility genes have been linked to CD, though their precise
      role in the pathogenesis of this disorder remains unclear. Immunity-related
      GTPase M (IRGM) is an established risk allele in CD. We have shown previously
      that conventionally raised (CV) mice lacking the IRGM ortholog, Irgm1 exhibit
      abnormal Paneth cells (PCs) and increased susceptibility to intestinal injury. In
      the present study, we sought to utilize this model system to determine if
      environmental conditions impact these phenotypes, as is thought to be the case in
      human CD. To accomplish this, wild-type and Irgm1-/- mice were rederived into
      specific pathogen-free (SPF) and germ-free (GF) conditions. We next assessed how
      these differential housing environments influenced intestinal injury patterns,
      and epithelial cell morphology and function in wild-type and Irgm1-/- mice.
      Remarkably, in contrast to CV mice, SPF Irgm1-/- mice showed only a slight
      increase in susceptibility to dextran sodium sulfate-induced inflammation. SPF
      Irgm1-/- mice also displayed minimal abnormalities in PC number and morphology,
      and in antimicrobial peptide expression. Goblet cell numbers and epithelial
      proliferation were also unaffected by Irgm1 in SPF conditions. No microbial
      differences were observed between wild-type and Irgm1-/- mice, but gut bacterial
      communities differed profoundly between CV and SPF mice. Specifically,
      Helicobacter sequences were significantly increased in CV mice; however,
      inoculating SPF Irgm1-/- mice with Helicobacter hepaticus was not sufficient to
      transmit a pro-inflammatory phenotype. In summary, our findings suggest the
      impact of Irgm1-deficiency on susceptibility to intestinal inflammation and
      epithelial function is critically dependent on environmental influences. This
      work establishes the importance of Irgm1-/- mice as a model to elucidate host
      environment interactions that regulate mucosal homeostasis and intestinal
      inflammatory responses. Defining such interactions will be essential for
      developing novel preventative and therapeutic strategies for human CD.

PMID- 29361513
TI  - Manipulation of dipeptidylpeptidase 10 in mouse and human in vivo and in vitro
      models indicates a protective role in asthma.
AB  - We previously identified dipeptidylpeptidase 10 (DPP10) on chromosome 2 as a
      human asthma susceptibility gene, through positional cloning. Initial association
      results were confirmed in many subsequent association studies but the functional
      role of DPP10 in asthma remains unclear. Using the MRC Harwell N-ethyl-N
      nitrosourea (ENU) DNA archive, we identified a point mutation in Dpp10 that
      caused an amino acid change from valine to aspartic acid in the beta-propeller
      region of the protein. Mice carrying this point mutation were recovered and a
      congenic line was established (Dpp10145D ). Macroscopic examination and lung
      histology revealed no significant differences between wild-type and
      Dpp10145D/145D mice. However, after house dust mite (HDM) treatment, Dpp10 mutant
      mice showed significantly increased airway resistance in response to 100 mg/ml
      methacholine. Total serum IgE levels and bronchoalveolar lavage (BAL) eosinophil
      counts were significantly higher in homozygotes than in control mice after HDM
      treatment. DPP10 protein is present in airway epithelial cells and altered
      expression is observed in both tissue from asthmatic patients and in mice
      following HDM challenge. Moreover, knockdown of DPP10 in human airway epithelial
      cells results in altered cytokine responses. These results show that a Dpp10
      point mutation leads to increased airway responsiveness following allergen
      challenge and provide biological evidence to support previous findings from human
      genetic studies. This article has an associated First Person interview with the
      first author of the paper.

PMID- 29361514
TI  - Inorganic arsenic causes fatty liver and interacts with ethanol to cause
      alcoholic liver disease in zebrafish.
AB  - The rapid increase in fatty liver disease (FLD) incidence is attributed largely
      to genetic and lifestyle factors; however, environmental toxicants are a
      frequently overlooked factor that can modify the effects of more common causes of
      FLD. Chronic exposure to inorganic arsenic (iAs) is associated with liver disease
      in humans and animal models, but neither the mechanism of action nor the
      combinatorial interaction with other disease-causing factors has been fully
      investigated. Here, we examined the contribution of iAs to FLD using zebrafish
      and tested the interaction with ethanol to cause alcoholic liver disease (ALD).
      We report that zebrafish exposed to iAs throughout development developed specific
      phenotypes beginning at 4 days post-fertilization (dpf), including the
      development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic
      analysis of livers from larvae exposed to either iAs or ethanol revealed the
      oxidative stress response and the unfolded protein response (UPR) caused by
      endoplasmic reticulum (ER) stress as common pathways in both these models of FLD,
      suggesting that they target similar cellular processes. This was confirmed by our
      finding that arsenic is synthetically lethal with both ethanol and a well
      characterized ER-stress-inducing agent (tunicamycin), suggesting that these
      exposures work together through UPR activation to cause iAs toxicity. Most
      significantly, combined exposure to sub-toxic concentrations of iAs and ethanol
      potentiated the expression of UPR-associated genes, cooperated to induce FLD,
      reduced the expression of as3mt, which encodes an arsenic-metabolizing enzyme,
      and significantly increased the concentration of iAs in the liver. This
      demonstrates that iAs exposure is sufficient to cause FLD and that low doses of
      iAs can potentiate the effects of ethanol to cause liver disease.This article has
      an associated First Person interview with the first author of the paper.

PMID- 29361515
TI  - Superior cervical gangliectomy induces non-exudative age-related macular
      degeneration in mice.
AB  - Non-exudative age-related macular degeneration, a prevalent cause of blindness,
      is a progressive and degenerative disease characterized by alterations in Bruch's
      membrane, retinal pigment epithelium, and photoreceptors exclusively localized in
      the macula. Although experimental murine models exist, the vast majority take a
      long time to develop retinal alterations and, in general, these alterations are
      ubiquitous, with many resulting from non-eye-specific genetic manipulations;
      additionally, most do not always reproduce the hallmarks of human age-related
      macular degeneration. Choroid vessels receive sympathetic innervation from the
      superior cervical ganglion, which, together with the parasympathetic system,
      regulates blood flow into the choroid. Choroid blood flow changes have been
      involved in age-related macular degeneration development and progression. At
      present, no experimental models take this factor into account. The aim of this
      work was to analyze the effect of superior cervical gangliectomy (also known as
      ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and
      retina. Adult male C57BL/6J mice underwent unilateral superior cervical
      gangliectomy and a contralateral sham procedure. Although superior cervical
      gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced
      Bruch's membrane thickening, loss of retinal pigment epithelium melanin content
      and retinoid isomerohydrolase, the appearance of drusen-like deposits, and
      retinal pigment epithelium and photoreceptor atrophy, exclusively localized in
      the temporal side. Moreover, superior cervical gangliectomy provoked a localized
      increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline
      in photoreceptor electroretinographic function. Therefore, superior cervical
      gangliectomy recapitulated the main features of human non-exudative age-related
      macular degeneration, and could become a new experimental model of dry age
      related macular degeneration, and a useful platform for developing new therapies.

PMID- 29361516
TI  - High-throughput screen for compounds that modulate neurite growth of human
      induced pluripotent stem cell-derived neurons.
AB  - Development of technology platforms to perform compound screens of human induced
      pluripotent stem cell (hiPSC)-derived neurons with relatively high throughput is
      essential to realize their potential for drug discovery. Here, we demonstrate the
      feasibility of high-throughput screening of hiPSC-derived neurons using a high
      content, image-based approach focused on neurite growth, a process that is
      fundamental to formation of neural networks and nerve regeneration. From a
      collection of 4421 bioactive small molecules, we identified 108 hit compounds,
      including 37 approved drugs, that target molecules or pathways known to regulate
      neurite growth, as well as those not previously associated with this process.
      These data provide evidence that many pathways and targets known to play roles in
      neurite growth have similar activities in hiPSC-derived neurons that can be
      identified in an unbiased phenotypic screen. The data also suggest that hiPSC
      derived neurons provide a useful system to study the mechanisms of action and off
      target activities of the approved drugs identified as hits, leading to a better
      understanding of their clinical efficacy and toxicity, especially in the context
      of specific human genetic backgrounds. Finally, the hit set we report constitutes
      a sublibrary of approved drugs and tool compounds that modulate neurites. This
      sublibrary will be invaluable for phenotypic analyses and interrogation of hiPSC
      based disease models as probes for defining phenotypic differences and cellular
      vulnerabilities in patient versus control cells, as well as for investigations of
      the molecular mechanisms underlying human neurite growth in development and
      maintenance of neuronal networks, and nerve regeneration.

PMID- 29361517
TI  - Inhibition of galectin-3 ameliorates the consequences of cardiac lipotoxicity in
      a rat model of diet-induced obesity.
AB  - Obesity is accompanied by metabolic alterations characterized by insulin
      resistance and cardiac lipotoxicity. Galectin-3 (Gal-3) induces cardiac
      inflammation and fibrosis in the context of obesity; however, its role in the
      metabolic consequences of obesity is not totally established. We have
      investigated the potential role of Gal-3 in the cardiac metabolic disturbances
      associated with obesity. In addition, we have explored whether this participation
      is, at least partially, acting on mitochondrial damage. Gal-3 inhibition in rats
      that were fed a high-fat diet (HFD) for 6 weeks with modified citrus pectin (MCP;
      100 mg/kg/day) attenuated the increase in cardiac levels of total triglyceride
      (TG). MCP treatment also prevented the increase in cardiac protein levels of
      carnitine palmitoyl transferase IA, mitofusin 1, and mitochondrial complexes I
      and II, reactive oxygen species accumulation and decrease in those of complex V
      but did not affect the reduction in 18F-fluorodeoxyglucose uptake observed in HFD
      rats. The exposure of cardiac myoblasts (H9c2) to palmitic acid increased the
      rate of respiration, mainly due to an increase in the proton leak, glycolysis,
      oxidative stress, beta-oxidation and reduced mitochondrial membrane potential.
      Inhibition of Gal-3 activity was unable to affect these changes. Our findings
      indicate that Gal-3 inhibition attenuates some of the consequences of cardiac
      lipotoxicity induced by a HFD since it reduced TG and lysophosphatidyl choline
      (LPC) levels. These reductions were accompanied by amelioration of the
      mitochondrial damage observed in HFD rats, although no improvement was observed
      regarding insulin resistance. These findings increase the interest for Gal-3 as a
      potential new target for therapeutic intervention to prevent obesity-associated
      cardiac lipotoxicity and subsequent mitochondrial dysfunction.

PMID- 29361518
TI  - The IgCAM CLMP regulates expression of Connexin43 and Connexin45 in intestinal
      and ureteral smooth muscle contraction in mice.
AB  - CAR-like membrane protein (CLMP), an immunoglobulin cell adhesion molecule
      (IgCAM), has been implicated in congenital short-bowel syndrome in humans, a
      condition with high mortality for which there is currently no cure. We therefore
      studied the function of CLMP in a Clmp-deficient mouse model. Although we found
      that the levels of mRNAs encoding Connexin43 or Connexin45 were not or were only
      marginally affected, respectively, by Clmp deficiency, the absence of CLMP caused
      a severe reduction of both proteins in smooth muscle cells of the intestine and
      of Connexin43 in the ureter. Analysis of calcium signaling revealed a disordered
      cell-cell communication between smooth muscle cells, which in turn induced an
      impaired and uncoordinated motility of the intestine and the ureter.
      Consequently, insufficient transport of chyme and urine caused a fatal delay to
      thrive, a high rate of mortality, and provoked a severe hydronephrosis in CLMP
      knockouts. Neurotransmission and the capability of smooth muscle cells to
      contract in ring preparations of the intestine were not altered. Physical
      obstructions were not detectable and an overall normal histology in the intestine
      as well as in the ureter was observed, except for a slight hypertrophy of smooth
      muscle layers. Deletion of Clmp did not lead to a reduced length of the intestine
      as shown for the human CLMP gene but resulted in gut malrotations. In sum, the
      absence of CLMP caused functional obstructions in the intestinal tract and ureter
      by impaired peristaltic contractions most likely due to a lack of gap-junctional
      communication between smooth muscle cells.

PMID- 29361519
TI  - Curcumin and derivatives function through protein phosphatase 2A and presenilin
      orthologues in Dictyostelium discoideum.
AB  - Natural compounds often have complex molecular structures and unknown molecular
      targets. These characteristics make them difficult to analyse using a classical
      pharmacological approach. Curcumin, the main curcuminoid of turmeric, is a
      complex molecule possessing wide-ranging biological activities, cellular
      mechanisms and roles in potential therapeutic treatment, including Alzheimer's
      disease and cancer. Here, we investigate the physiological effects and molecular
      targets of curcumin in Dictyostelium discoideum We show that curcumin exerts
      acute effects on cell behaviour, reduces cell growth and slows multicellular
      development. We employed a range of structurally related compounds to show the
      distinct role of different structural groups in curcumin's effects on cell
      behaviour, growth and development, highlighting active moieties in cell function,
      and showing that these cellular effects are unrelated to the well-known
      antioxidant activity of curcumin. Molecular mechanisms underlying the effect of
      curcumin and one synthetic analogue (EF24) were then investigated to identify a
      curcumin-resistant mutant lacking the protein phosphatase 2A regulatory subunit
      (PsrA) and an EF24-resistant mutant lacking the presenilin 1 orthologue (PsenB).
      Using in silico docking analysis, we then showed that curcumin might function
      through direct binding to a key regulatory region of PsrA. These findings reveal
      novel cellular and molecular mechanisms for the function of curcumin and related
      compounds.

PMID- 29361520
TI  - Divergent effects of adrenaline in human induced pluripotent stem cell-derived
      cardiomyocytes obtained from hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that
      affects the heart muscle with diverse clinical outcomes. HCM can cause sudden
      cardiac death (SCD) during or immediately after mild to rigorous physical
      activity in young patients. However, the mechanism causing SCD as a result of
      exercise remains unknown, but exercise-induced ventricular arrhythmias are
      thought to be responsible for this fatal consequence. To understand the disease
      mechanism behind HCM in a better way, we generated patient-specific induced
      pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients
      carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively
      investigated the effects of low to high concentrations of adrenaline on action
      potential characteristics, and the occurrence of arrhythmias in the presence of
      various concentrations of adrenaline and in wash-out condition. We classified and
      quantified different types of arrhythmias observed in hiPSC-CMs, and found that
      the occurrence of arrhythmias was dependent on concentrations of adrenaline and
      positions of mutations in genes causing HCM. In addition, we observed ventricular
      tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn
      mutation. We additionally examined the antiarrhythmic potency of bisoprolol in
      HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of
      arrhythmias during administration or during the wash-out condition of adrenaline
      in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool
      for studying HCM. The experimental design used in this study could be suitable
      and beneficial for studying other components and drugs related to cardiac disease
      in general.

PMID- 29361521
TI  - Developmental abnormalities in supporting cell phalangeal processes and
      cytoskeleton in the Gjb2 knockdown mouse model.
AB  - Mutations in the GJB2 gene [which encodes connexin 26 (Cx26)] are the most common
      causes of hereditary hearing loss in humans, and previous studies showed
      postnatal development arrest of the organ of Corti in different Cx26-null mouse
      models. To explore the pathological changes and the mechanism behind the cochlear
      abnormalities in these mice further, we established transgenic mouse models by
      conditional knockdown of cochlear Cx26 at postnatal day (P) 0 and P8. Auditory
      brainstem responses were recorded and the morphological features in the organ of
      Corti were analyzed 18 days after Cx26 knockdown. Mice in the P0 knockdown group
      displayed severe hearing loss at all frequencies, whereas mice in the P8
      knockdown group showed nearly normal hearing. In the P8 knockdown group, the
      organ of Corti displayed normal architecture, and no ultrastructural changes were
      observed. In the P0 knockdown group, the phalangeal processes of Deiter's cells
      did not develop into finger-like structures, and the formation of microtubules in
      the pillar cells was significantly reduced; moreover, the amount of acetylated
      alpha-tubulin was reduced in pillar cells. Our results indicate that Gjb2
      participates in postnatal development of the cytoskeleton in pillar cells during
      structural maturation of the organ of Corti. In P0 knockdown mice, the reduction
      in microtubules in pillar cells might be responsible for the failure of the
      tunnel of Corti to open, and the malformed phalangeal processes might negatively
      affect the supporting framework of the organ of Corti, which would be a new
      mechanism of Gjb2-related hearing loss.

PMID- 29361523
TI  - The feedback loop between miR-21, PDCD4 and AP-1 functions as a driving force for
      renal fibrogenesis.
AB  - Renal fibrosis is a final common pathway of chronic kidney disease. Sustained
      activation of fibroblasts is considered to play a key role in perpetuating renal
      fibrosis but the driving force in the perpetuation stage is only partially
      understood. To date, some investigations have specifically identified
      overexpression of microRNA 21 (miR-21) in the progression of kidney fibrosis.
      Nevertheless, the precise role of miR-21 in fibroblast activation remains largely
      unknown. In this study, we found that miR-21 was significantly upregulated in
      activated fibroblasts and that it maintained itself at constant high levels by
      employing an auto-regulatory loop between miR-21, PDCD4 and AP-1. Persistently
      upregulated miR-21 suppressed protein expression of Smad7 and, eventually,
      enhanced the TGF-beta1/Smad pathway to promote fibroblast activation. More
      importantly, we found miR-21 sequestration with miR-21 antagomir or AP-1
      inhibitors attenuated unilateral ureteral obstruction (UUO)-induced renal
      fibrosis. miR-21-knockout mice also suffered far less interstitial fibrosis in
      response to kidney injury. Altogether, these data suggest that miR-21 is a main
      driving force of fibroblast activation and keeps its high expression level by
      employing a double negative autoregulatory loop. Targeting this aberrantly
      activated feedback loop may provide new therapeutic strategy in treating fibrotic
      kidneys.

PMID- 29361522
TI  - The fibronectin ED-A domain enhances recruitment of latent TGF-beta-binding
      protein-1 to the fibroblast matrix.
AB  - Dysregulated secretion and extracellular activation of TGF-beta1 stimulates
      myofibroblasts to accumulate disordered and stiff extracellular matrix (ECM)
      leading to fibrosis. Fibronectin immobilizes latent TGF-beta-binding protein-1
      (LTBP-1) and thus stores TGF-beta1 in the ECM. Because the ED-A fibronectin
      splice variant is prominently expressed during fibrosis and supports
      myofibroblast activation, we investigated whether ED-A promotes LTBP-1
      fibronectin interactions. Using stiffness-tuneable substrates for human dermal
      fibroblast cultures, we showed that high ECM stiffness promotes expression and
      colocalization of LTBP-1 and ED-A-containing fibronectin. When rescuing
      fibronectin-depleted fibroblasts with specific fibronectin splice variants, LTBP
      1 bound more efficiently to ED-A-containing fibronectin than to ED-B-containing
      fibronectin and fibronectin lacking splice domains. Function blocking of the ED-A
      domain using antibodies and competitive peptides resulted in reduced LTBP-1
      binding to ED-A-containing fibronectin, reduced LTBP-1 incorporation into the
      fibroblast ECM and reduced TGF-beta1 activation. Similar results were obtained by
      blocking the heparin-binding stretch FNIII12-13-14 (HepII), adjacent to the ED-A
      domain in fibronectin. Collectively, our results suggest that the ED-A domain
      enhances association of the latent TGF-beta1 by promoting weak direct binding to
      LTBP-1 and by enhancing heparin-mediated protein interactions through HepII in
      fibronectin.

PMID- 29361524
TI  - F-box proteins Pof3 and Pof1 regulate Wee1 degradation and mitotic entry in
      fission yeast.
AB  - The key cyclin-dependent kinase Cdk1 (Cdc2) promotes irreversible mitotic entry,
      mainly by activating the phosphatase Cdc25 while suppressing the tyrosine kinase
      Wee1. Wee1 needs to be downregulated at the onset of mitosis to ensure rapid
      activation of Cdk1. In human somatic cells, one mechanism of suppressing Wee1
      activity is mediated by ubiquitylation-dependent proteolysis through the
      Skp1/Cul1/F-box protein (SCF) ubiquitin E3 ligase complex. This mechanism is
      believed to be conserved from yeasts to humans. So far, the best-characterized
      human F-box proteins involved in recognition of Wee1 are beta-TrCP (BTRCP) and
      Tome-1 (CDCA3). Although fission yeast Wee1 was the first identified member of
      its conserved kinase family, the F-box proteins involved in recognition and
      ubiquitylation of Wee1 have not been identified in this organism. In this study,
      our screen using Wee1-Renilla luciferase as the reporter revealed that two F-box
      proteins, Pof1 and Pof3, are required for downregulating Wee1 and are possibly
      responsible for recruiting Wee1 to SCF. Our genetic analyses supported a
      functional relevance between Pof1 and Pof3 and the rate of mitotic entry, and
      Pof3 might play a major role in this process.

PMID- 29361525
TI  - Stress-activated MAPKs and CRM1 regulate the subcellular localization of Net1A to
      control cell motility and invasion.
AB  - The neuroepithelial cell transforming gene 1A (Net1A, an isoform of Net1) is a
      RhoA subfamily guanine nucleotide exchange factor (GEF) that localizes to the
      nucleus in the absence of stimulation, preventing it from activating RhoA. Once
      relocalized in the cytosol, Net1A stimulates cell motility and extracellular
      matrix invasion. In the present work, we investigated mechanisms responsible for
      the cytosolic relocalization of Net1A. We demonstrate that inhibition of MAPK
      pathways blocks Net1A relocalization, with cells being most sensitive to JNK
      pathway inhibition. Moreover, activation of the JNK or p38 MAPK family pathway is
      sufficient to elicit Net1A cytosolic localization. Net1A relocalization
      stimulated by EGF or JNK activation requires nuclear export mediated by CRM1.
      JNK1 (also known as MAPK8) phosphorylates Net1A on serine 52, and alanine
      substitution at this site prevents Net1A relocalization caused by EGF or JNK
      activation. Glutamic acid substitution at this site is sufficient for Net1A
      relocalization and results in elevated RhoA signaling to stimulate myosin light
      chain 2 (MLC2, also known as MYL2) phosphorylation and F-actin accumulation.
      Net1A S52E expression stimulates cell motility, enables Matrigel invasion and
      promotes invadopodia formation. These data highlight a novel mechanism for
      controlling the subcellular localization of Net1A to regulate RhoA activation,
      cell motility, and invasion.

PMID- 29361526
TI  - Calcium signaling mediates five types of cell morphological changes to form
      neural rosettes.
AB  - Neural rosette formation is a critical morphogenetic process during neural
      development, whereby neural stem cells are enclosed in rosette niches to
      equipoise proliferation and differentiation. How neural rosettes form and provide
      a regulatory micro-environment remains to be elucidated. We employed the human
      embryonic stem cell-based neural rosette system to investigate the structural
      development and function of neural rosettes. Our study shows that neural rosette
      formation consists of five types of morphological change: intercalation,
      constriction, polarization, elongation and lumen formation. Ca2+ signaling plays
      a pivotal role in the five steps by regulating the actions of the cytoskeletal
      complexes, actin, myosin II and tubulin during intercalation, constriction and
      elongation. These, in turn, control the polarizing elements, ZO-1, PARD3 and beta
      catenin during polarization and lumen production for neural rosette formation. We
      further demonstrate that the dismantlement of neural rosettes, mediated by the
      destruction of cytoskeletal elements, promotes neurogenesis and astrogenesis
      prematurely, indicating that an intact rosette structure is essential for orderly
      neural development.

PMID- 29361527
TI  - alpha5beta1 integrin trafficking and Rac activation are regulated by APPL1 in a
      Rab5-dependent manner to inhibit cell migration.
AB  - Cell migration is a tightly coordinated process that requires the spatiotemporal
      regulation of many molecular components. Because adaptor proteins can serve as
      integrators of cellular events, they are being increasingly studied as regulators
      of cell migration. The adaptor protein containing a pleckstrin-homology (PH)
      domain, phosphotyrosine binding (PTB) domain, and leucine zipper motif 1 (APPL1)
      is a 709 amino acid endosomal protein that plays a role in cell proliferation and
      survival as well as endosomal trafficking and signaling. However, its function in
      regulating cell migration is poorly understood. Here, we show that APPL1 hinders
      cell migration by modulating both trafficking and signaling events controlled by
      Rab5 in cancer cells. APPL1 decreases internalization and increases recycling of
      alpha5beta1 integrin, leading to higher levels of alpha5beta1 integrin at the
      cell surface that hinder adhesion dynamics. Furthermore, APPL1 decreases the
      activity of the GTPase Rac and its effector PAK, which in turn regulate cell
      migration. Thus, we demonstrate a novel role for the interaction between APPL1
      and Rab5 in governing crosstalk between signaling and trafficking pathways on
      endosomes to affect cancer cell migration.This article has an associated First
      Person interview with the first author of the paper.

PMID- 29361528
TI  - Dileucine-like motifs in the C-terminal tail of connexin32 control its
      endocytosis and assembly into gap junctions.
AB  - Defects in assembly of gap junction-forming proteins, called connexins (Cxs), are
      observed in a variety of cancers. Connexin32 (Cx32; also known as GJB1) is
      expressed by the polarized cells in epithelia. We discovered two dileucine-based
      motifs, which govern the intracellular sorting and endocytosis of transmembrane
      proteins, in the C-terminal tail of Cx32 and explored their role in regulating
      its endocytosis and gap junction-forming abilities in pancreatic and prostate
      cancer cells. One motif, designated as LI, was located near the juxtamembrane
      domain, whereas the other, designated as LL, was located distally. We also
      discovered a non-canonical motif, designated as LR, in the C-terminal tail. Our
      results showed that rendering these motifs non-functional had no effect on the
      intracellular sorting of Cx32. However, rendering the LL or LR motif
      nonfunctional enhanced the formation of gap junctions by inhibiting Cx32
      endocytosis by the clathrin-mediated pathway. Rendering the LI motif
      nonfunctional inhibited gap junction formation by augmenting the endocytosis of
      Cx32 via the LL and LR motifs. Our studies have defined distinct roles of these
      motifs in regulating the endocytosis of Cx32 and its gap junction-forming
      ability.This article has an associated First Person interview with the first
      author of the paper.

PMID- 29361529
TI  - Yeast cells contain a heterogeneous population of peroxisomes that segregate
      asymmetrically during cell division.
AB  - Here, we used fluorescence microscopy and a peroxisome-targeted tandem
      fluorescent protein timer to determine the relative age of peroxisomes in yeast.
      Our data indicate that yeast cells contain a heterogeneous population of
      relatively old and young peroxisomes. During budding, the peroxisome retention
      factor inheritance of peroxisomes protein 1 (Inp1) selectively associates to the
      older organelles, which are retained in the mother cells. Inp2, a protein
      required for transport of peroxisomes to the bud, preferentially associates to
      younger organelles. Using a microfluidics device, we demonstrate that the
      selective segregation of younger peroxisomes to the buds is carefully maintained
      during multiple budding events. The replicative lifespan of mother cells
      increased upon deletion of INP2, which resulted in the retention of all
      organelles in mother cells. These data suggest that, in wild-type yeast,
      transport of aged and deteriorated peroxisomes to the bud is prevented, whereas
      the young and vital organelles are preferably transported to the newly forming
      buds.

PMID- 29361530
TI  - Non-equivalence of nuclear import among nuclei in multinucleated skeletal muscle
      cells.
AB  - Skeletal muscle is primarily composed of large myofibers containing thousands of
      post-mitotic nuclei distributed throughout a common cytoplasm. Protein production
      and localization in specialized myofiber regions is crucial for muscle function.
      Myonuclei differ in transcriptional activity and protein accumulation, but how
      these differences among nuclei sharing a cytoplasm are achieved is unknown.
      Regulated nuclear import of proteins is one potential mechanism for regulating
      transcription spatially and temporally in individual myonuclei. The best
      characterized nuclear localization signal (NLS) in proteins is the classical NLS
      (cNLS), but many other NLS motifs exist. We examined cNLS and non-cNLS reporter
      protein import using multinucleated muscle cells generated in vitro, revealing
      that cNLS and non-cNLS nuclear import differs among nuclei in the same cell.
      Investigation of cNLS nuclear import rates in isolated myofibers ex vivo
      confirmed differences in nuclear import rates among myonuclei. Analyzing nuclear
      import throughout myogenesis revealed that cNLS and non-cNLS import varies during
      differentiation. Taken together, our results suggest that both spatial and
      temporal regulation of nuclear import pathways are important in muscle cell
      differentiation and protein regionalization in myofibers.

PMID- 29361531
TI  - Epithelial and stromal circadian clocks are inversely regulated by their mechano
      matrix environment.
AB  - The circadian clock is an autonomous molecular feedback loop inside almost every
      cell in the body. We have shown that the mammary epithelial circadian clock is
      regulated by the cellular microenvironment. Moreover, a stiff extracellular
      matrix dampens the oscillations of the epithelial molecular clock. Here, we
      extend this analysis to other tissues and cell types, and identify an inverse
      relationship between circadian clocks in epithelia and fibroblasts. Epithelial
      cells from mammary gland, lung and skin have significantly stronger oscillations
      of clock genes in soft 3D microenvironments, compared to stiff 2D environments.
      Fibroblasts isolated from the same tissues show the opposite response, exhibiting
      stronger oscillations and more prolonged rhythmicity in stiff microenvironments.
      RNA analysis identified that a subset of mammary epithelial clock genes, and
      their regulators, are upregulated in 3D microenvironments in soft compared to
      stiff gels. Furthermore, the same genes are inversely regulated in fibroblasts
      isolated from the same tissues. Thus, our data reveal for the first time an
      intrinsic difference in the regulation of circadian genes in epithelia and
      fibroblasts.

PMID- 29361532
TI  - Nucleoplasmic lamins define growth-regulating functions of lamina-associated
      polypeptide 2alpha in progeria cells.
AB  - A-type lamins are components of the peripheral nuclear lamina but also localize
      in the nuclear interior in a complex with lamina-associated polypeptide (LAP)
      2alpha. Loss of LAP2alpha and nucleoplasmic lamins in wild-type cells increases
      cell proliferation, but in cells expressing progerin (a mutant lamin A that
      causes Hutchinson-Gilford progeria syndrome), low LAP2alpha levels result in
      proliferation defects. Here, the aim was to understand the molecular mechanism
      governing how relative levels of LAP2alpha, progerin and nucleoplasmic lamins
      affect cell proliferation. Cells from progeria patients and inducible progerin
      expressing cells expressing low levels of progerin proliferate faster than wild
      type or lamin A-expressing control cells, and ectopic expression of LAP2alpha
      impairs proliferation. In contrast, cells expressing high levels of progerin and
      lacking lamins in the nuclear interior proliferate more slowly, and ectopic
      LAP2alpha expression enhances proliferation. However, simultaneous expression of
      LAP2alpha and wild-type lamin A or an assembly-deficient lamin A mutant restored
      the nucleoplasmic lamin A pool in these cells and abolished the growth-promoting
      effect of LAP2alpha. Our data show that LAP2alpha promotes or inhibits
      proliferation of progeria cells depending on the level of A-type lamins in the
      nuclear interior.This article has an associated First Person interview with the
      first author of the paper.

PMID- 29361533
TI  - Role of membrane-tension gated Ca2+ flux in cell mechanosensation.
AB  - Eukaryotic cells are sensitive to mechanical forces they experience from the
      environment. The process of mechanosensation is complex, and involves elements
      such as the cytoskeleton and active contraction from myosin motors. Ultimately,
      mechanosensation is connected to changes in gene expression in the cell, known as
      mechanotransduction. While the involvement of the cytoskeleton in
      mechanosensation is known, the processes upstream of cytoskeletal changes are
      unclear. In this paper, by using a microfluidic device that mechanically
      compresses live cells, we demonstrate that Ca2+ currents and membrane tension
      sensitive ion channels directly signal to the Rho GTPase and myosin contraction.
      In response to membrane tension changes, cells actively regulate cortical myosin
      contraction to balance external forces. The process is captured by a
      mechanochemical model where membrane tension, myosin contraction and the osmotic
      pressure difference between the cytoplasm and extracellular environment are
      connected by mechanical force balance. Finally, to complete the picture of
      mechanotransduction, we find that the tension-sensitive transcription factor YAP
      family of proteins translocate from the nucleus to the cytoplasm in response to
      mechanical compression.

PMID- 29361534
TI  - Drp1 polymerization stabilizes curved tubular membranes similar to those of
      constricted mitochondria.
AB  - Dynamin-related protein 1 (Drp1), an 80 kDa mechanochemical GTPase of the dynamin
      superfamily, is required for mitochondrial division in mammals. Despite the role
      of Drp1 dysfunction in human disease, its molecular mechanism remains poorly
      understood. Here, we examined the effect of Drp1 on membrane curvature using
      tubes pulled from giant unilamellar vesicles (GUVs). We found that GTP promoted
      rapid rearrangement of Drp1 from a uniform distribution to discrete foci, in line
      with the assembly of Drp1 scaffolds at multiple nucleation sites around the lipid
      tube. Polymerized Drp1 preserved the membrane tube below the protein coat, also
      in the absence of pulling forces, but did not induce spontaneous membrane
      fission. Strikingly, Drp1 polymers stabilized membrane curvatures similar to
      those of constricted mitochondria against pressure changes. Our findings support
      a new model for mitochondrial division whereby Drp1 mainly acts as a scaffold for
      membrane curvature stabilization, which sets it apart from other dynamin
      homologs.

PMID- 29361535
TI  - Regulation of profibrotic responses by ADAM17 activation in high glucose requires
      its C-terminus and FAK.
AB  - Glomerular matrix accumulation is the hallmark of diabetic nephropathy. The
      metalloprotease ADAM17 mediates high glucose (HG)-induced matrix production by
      kidney mesangial cells through release of ligands for the epidermal growth factor
      receptor. Here, we study the mechanism by which HG activates ADAM17. We find that
      the C-terminus is essential for ADAM17 activation and the profibrotic response to
      HG. In the C-terminus, Src-mediated Y702 phosphorylation and PI3K-MEK-Erk
      mediated T735 phosphorylation are crucial for ADAM17 activation, both are also
      required for the HG-induced increase in cell surface mature ADAM17. The non
      receptor tyrosine kinase FAK is a central mediator of these processes. These data
      not only support a crucial role for the C-terminus in ADAM17 activation and
      downstream profibrotic responses to HG, but also highlight FAK as a potential
      alternative therapeutic target for diabetic nephropathy.

PMID- 29361537
TI  - Septins are involved at the early stages of macroautophagy in S. cerevisiae.
AB  - Autophagy is a conserved cellular degradation pathway wherein double-membrane
      vesicles called autophagosomes capture long-lived proteins, and damaged or
      superfluous organelles, and deliver them to the lysosome for degradation. Septins
      are conserved GTP-binding proteins involved in many cellular processes, including
      phagocytosis and the autophagy of intracellular bacteria, but no role in general
      autophagy was known. In budding yeast, septins polymerize into ring-shaped arrays
      of filaments required for cytokinesis. In an unbiased genetic screen and in
      subsequent targeted analysis, we found autophagy defects in septin mutants. Upon
      autophagy induction, pre-assembled septin complexes relocalized to the pre
      autophagosomal structure (PAS) where they formed non-canonical septin rings at
      PAS. Septins also colocalized with autophagosomes, where they physically
      interacted with the autophagy proteins Atg8 and Atg9. When autophagosome
      degradation was blocked in septin-mutant cells, fewer autophagic structures
      accumulated, and an autophagy mutant defective in early stages of autophagosome
      biogenesis (atg1Delta), displayed decreased septin localization to the PAS. Our
      findings support a role for septins in the early stages of budding yeast
      autophagy, during autophagosome formation.This article has an associated First
      Person interview with the first author of the paper.

PMID- 29361538
TI  - Green light for quantitative live-cell imaging in plants.
AB  - Plants exhibit an intriguing morphological and physiological plasticity that
      enables them to thrive in a wide range of environments. To understand the cell
      biological basis of this unparalleled competence, a number of methodologies have
      been adapted or developed over the last decades that allow minimal or non
      invasive live-cell imaging in the context of tissues. Combined with the ease to
      generate transgenic reporter lines in specific genetic backgrounds or accessions,
      we are witnessing a blooming in plant cell biology. However, the imaging of plant
      cells entails a number of specific challenges, such as high levels of
      autofluorescence, light scattering that is caused by cell walls and their
      sensitivity to environmental conditions. Quantitative live-cell imaging in plants
      therefore requires adapting or developing imaging techniques, as well as mounting
      and incubation systems, such as micro-fluidics. Here, we discuss some of these
      obstacles, and review a number of selected state-of-the-art techniques, such as
      two-photon imaging, light sheet microscopy and variable angle epifluorescence
      microscopy that allow high performance and minimal invasive live-cell imaging in
      plants.

PMID- 29361536
TI  - FGF2-dependent mesenchyme and laminin-111 are niche factors in salivary gland
      organoids.
AB  - Epithelial progenitor cells are dependent upon a complex 3D niche to promote
      their proliferation and differentiation during development, which can be
      recapitulated in organoids. The specific requirements of the niche remain unclear
      for many cell types, including the proacinar cells that give rise to secretory
      acinar epithelial cells that produce saliva. Here, using ex vivo cultures of E16
      primary mouse submandibular salivary gland epithelial cell clusters, we
      investigated the requirement for mesenchymal cells and other factors in producing
      salivary organoids in culture. Native E16 salivary mesenchyme, but not NIH3T3
      cells or mesenchymal cell conditioned medium, supported robust protein expression
      of the progenitor marker Kit and the acinar/proacinar marker AQP5, with a
      requirement for FGF2 expression by the mesenchyme. Enriched salivary epithelial
      clusters that were grown in laminin-enriched basement membrane extract or laminin
      111 together with exogenous FGF2, but not with EGF, underwent morphogenesis to
      form organoids that displayed robust expression of AQP5 in terminal buds.
      Knockdown of FGF2 in the mesenchyme or depletion of mesenchyme cells from the
      organoids significantly reduced AQP5 levels even in the presence of FGF2,
      suggesting a requirement for autocrine FGF2 signaling in the mesenchyme cells for
      AQP5 expression. We conclude that basement membrane proteins and mesenchyme cells
      function as niche factors in salivary organoids.

PMID- 29361539
TI  - Glycans modify mesenchymal stem cell differentiation to impact on the function of
      resulting osteoblasts.
AB  - Glycans are inherently heterogeneous, yet glycosylation is essential in
      eukaryotes, and glycans show characteristic cell type-dependent distributions. By
      using an immortalized human mesenchymal stromal cell (MSC) line model, we show
      that both N- and O-glycan processing in the Golgi functionally modulates early
      steps of osteogenic differentiation. We found that inhibiting O-glycan processing
      in the Golgi prior to the start of osteogenesis inhibited the mineralization
      capacity of the formed osteoblasts 3 weeks later. In contrast, inhibition of N
      glycan processing in MSCs altered differentiation to enhance the mineralization
      capacity of the osteoblasts. The effect of N-glycans on MSC differentiation was
      mediated by the phosphoinositide-3-kinase (PI3K)/Akt pathway owing to reduced Akt
      phosphorylation. Interestingly, by inhibiting PI3K during the first 2 days of
      osteogenesis, we were able to phenocopy the effect of inhibiting N-glycan
      processing. Thus, glycan processing provides another layer of regulation that can
      modulate the functional outcome of differentiation. Glycan processing can thereby
      offer a novel set of targets for many therapeutically attractive processes.

PMID- 29361540
TI  - Unconventional myosin VIIA promotes melanoma progression.
AB  - Unconventional myosin VIIA (Myo7a) is an actin-based motor molecule that normally
      functions in the cochlear hair cells of the inner ear. Mutations of MYO7A/Myo7a
      have been implicated in inherited deafness in both humans and mice. However,
      there is limited information about the functions of Myo7a outside of the
      specialized cells of the ears. Herein, we report a previously unidentified
      function of Myo7a by demonstrating that it plays an important role in melanoma
      progression. We found that silencing Myo7a by means of RNAi inhibited melanoma
      cell growth through upregulation of cell cycle regulator p21 (also known as
      CDKN1A) and suppressed melanoma cell migration and invasion through
      downregulation of RhoGDI2 (also known as ARHGDIB) and MMP9. Furthermore, Myo7a
      depletion suppressed melanoma cell metastases to the lung, kidney and bone in
      mice. In contrast, overexpression of Myo7a promoted melanoma xenograft growth and
      lung metastasis. Importantly, Myo7a levels are remarkably elevated in human
      melanoma patients. Collectively, we demonstrated for the first time that Myo7a is
      able to function in non-specialized cells, a finding that reveals the complicated
      disease-related roles of Myo7a, especially in melanomas.

PMID- 29361541
TI  - Functional analysis after rapid degradation of condensins and 3D-EM reveals
      chromatin volume is uncoupled from chromosome architecture in mitosis.
AB  - The requirement for condensin in chromosome formation in somatic cells remains
      unclear, as imperfectly condensed chromosomes do form in cells depleted of
      condensin by conventional methodologies. In order to dissect the roles of
      condensin at different stages of vertebrate mitosis, we have established a
      versatile cellular system that combines auxin-mediated rapid degradation with
      chemical genetics to obtain near-synchronous mitotic entry of chicken DT40 cells
      in the presence and absence of condensin. We analyzed the outcome by live- and
      fixed-cell microscopy methods, including serial block face scanning electron
      microscopy with digital reconstruction. Following rapid depletion of condensin,
      chromosomal defects were much more obvious than those seen after a slow depletion
      of condensin. The total mitotic chromatin volume was similar to that in control
      cells, but a single mass of mitotic chromosomes was clustered at one side of a
      bent mitotic spindle. Cultures arrest at prometaphase, eventually exiting mitosis
      without segregating chromosomes. Experiments where the auxin concentration was
      titrated showed that different condensin levels are required for anaphase
      chromosome segregation and formation of a normal chromosome architecture.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 29361542
TI  - The ARF guanine nucleotide exchange factor GBF1 is targeted to Golgi membranes
      through a PIP-binding domain.
AB  - ADP-ribosylation factors (ARF) GTPases are activated by guanine nucleotide
      exchange factors (GEFs) to support cellular homeostasis. Key to understanding
      spatio-temporal regulation of ARF signaling is the mechanism of GEF recruitment
      to membranes. Small GEFs are recruited through phosphoinositide (PIP) binding by
      a pleckstrin homology (PH) domain downstream from the catalytic Sec7 domain
      (Sec7d). The large GEFs lack PH domains, and their recruitment mechanisms are
      poorly understood. We probed Golgi recruitment of GBF1, a GEF catalyzing ARF
      activation required for Golgi homeostasis. We show that the homology downstream
      of Sec7d-1 (HDS1) regulates Golgi recruitment of GBF1. We document that GBF1
      binds phosphoinositides, preferentially PI3P, PI4P and PI(4,5)P2, and that lipid
      binding requires the HDS1 domain. Mutations within HDS1 that reduce GBF1 binding
      to specific PIPs in vitro inhibit GBF1 targeting to Golgi membranes in cells. Our
      data imply that HDS1 and PH domains are functionally analogous in that each uses
      lipid-based membrane information to regulate GEF recruitment. Lipid-based
      recruitment of GBF1 extends the paradigm of lipid regulation to small and large
      GEFs and suggests that lipid-based mechanisms evolved early during GEF
      diversification. This article has an associated First Person interview with the
      first author of the paper.

PMID- 29361544
TI  - Axonal endoplasmic reticulum is very narrow.
AB  - The endoplasmic reticulum (ER) is an interconnected network of tubules and
      sheets. In most tissues of the body, ER tubules have a diameter of ~60 nm. Using
      new methods for serial-section electron microscopy, a distinct class of very
      narrow, 20- to 30-nm-diameter tubules were found in neurons of both the central
      and peripheral nervous system. The narrow tubules appear to be the most abundant
      form of ER in axons, and are also found interspersed in the cell bodies and
      dendrites. At the site of branch points, there is a small sheet that has a
      similarly narrow lumen. The narrowness of the ER is likely to be important for
      the as yet poorly characterized functions of the axonal ER.

PMID- 29361543
TI  - Mechano-sensitization of mammalian neuronal networks through expression of the
      bacterial large-conductance mechanosensitive ion channel.
AB  - Development of remote stimulation techniques for neuronal tissues represents a
      challenging goal. Among the potential methods, mechanical stimuli are the most
      promising vectors to convey information non-invasively into intact brain tissue.
      In this context, selective mechano-sensitization of neuronal circuits would pave
      the way to develop a new cell-type-specific stimulation approach. We report here,
      for the first time, the development and characterization of mechano-sensitized
      neuronal networks through the heterologous expression of an engineered bacterial
      large-conductance mechanosensitive ion channel (MscL). The neuronal functional
      expression of the MscL was validated through patch-clamp recordings upon
      application of calibrated suction pressures. Moreover, we verified the effective
      development of in-vitro neuronal networks expressing the engineered MscL in terms
      of cell survival, number of synaptic puncta and spontaneous network activity. The
      pure mechanosensitivity of the engineered MscL, with its wide genetic
      modification library, may represent a versatile tool to further develop a mechano
      genetic approach.This article has an associated First Person interview with the
      first author of the paper.

PMID- 29361546
TI  - A 'molecular guillotine' reveals the interphase function of Kinesin-5.
AB  - Motor proteins are important for transport and force generation in a variety of
      cellular processes and in morphogenesis. Here, we describe a general strategy for
      conditional motor mutants by inserting a protease cleavage site into the 'neck'
      between the head domain and the stalk of the motor protein, making the protein
      susceptible to proteolytic cleavage at the neck by the corresponding protease. To
      demonstrate the feasibility of this approach, we inserted the cleavage site of
      the tobacco etch virus (TEV) protease into the neck of the tetrameric motor
      Kinesin-5. Application of TEV protease led to a specific depletion and functional
      loss of Kinesin-5 in Drosophila embryos. With our approach, we revealed that
      Kinesin-5 stabilizes the microtubule network during interphase in syncytial
      embryos. The 'molecular guillotine' can potentially be applied to many motor
      proteins because Kinesins and myosins have conserved structures with accessible
      neck regions.This article has an associated First Person interview with the first
      author of the paper.

PMID- 29361547
TI  - 3D correlative electron microscopy reveals continuity of Brucella-containing
      vacuoles with the endoplasmic reticulum.
AB  - Entry of the facultative intracellular pathogen Brucella into host cells results
      in the formation of endosomal Brucella-containing vacuoles (eBCVs) that initially
      traffic along the endocytic pathway. eBCV acidification triggers the expression
      of a type IV secretion system that translocates bacterial effector proteins into
      host cells. This interferes with lysosomal fusion of eBCVs and supports their
      maturation to replicative Brucella-containing vacuoles (rBCVs). Bacteria
      replicate in rBCVs to large numbers, eventually occupying most of the cytoplasmic
      volume. As rBCV membranes tightly wrap each individual bacterium, they are
      constantly being expanded and remodeled during exponential bacterial growth.
      rBCVs are known to carry endoplasmic reticulum (ER) markers; however, the
      relationship of the vacuole to the genuine ER has remained elusive. Here, we have
      reconstructed the 3-dimensional ultrastructure of rBCVs and associated ER by
      correlative structured illumination microscopy (SIM) and focused ion
      beam/scanning electron microscopic tomography (FIB/SEM). Studying B. abortus
      infected HeLa cells and trophoblasts derived from B. melitensis-infected mice, we
      demonstrate that rBCVs are complex and interconnected compartments that are
      continuous with neighboring ER cisternae, thus supporting a model that rBCVs are
      extensions of genuine ER.

PMID- 29361545
TI  - Abscisic acid - an anti-angiogenic phytohormone that modulates the phenotypical
      plasticity of endothelial cells and macrophages.
AB  - Abscisic acid (ABA) has shown anti-inflammatory and immunoregulatory properties
      in preclinical models of diabetes and inflammation. Herein, we studied the
      effects of ABA on angiogenesis, a strictly controlled process that, when
      dysregulated, leads to severe angiogenic disorders including vascular overgrowth,
      exudation, cellular inflammation and organ dysfunction. By using a 3D sprouting
      assay, we show that ABA effectively inhibits migration, growth and expansion of
      endothelial tubes without affecting cell viability. Analyses of the retinal
      vasculature in developing normoxic and hyperoxic mice challenged by oxygen
      toxicity reveal that exogenously administered ABA stunts the development and
      regeneration of blood vessels. In these models, ABA downregulates endothelial
      cell (EC)-specific growth and migratory genes, interferes with tip and stalk cell
      specification, and hinders the function of filopodial protrusions required for
      precise guidance of vascular sprouts. In addition, ABA skews macrophage
      polarization towards the M1 phenotype characterized by anti-angiogenic marker
      expression. In accordance with this, ABA treatment accelerates macrophage-induced
      programmed regression of fetal blood vessels. These findings reveal protective
      functions of ABA against neovascular growth through modulation of EC and
      macrophage plasticity, suggesting the potential utility of ABA as a treatment in
      vasoproliferative diseases.

PMID- 29361548
TI  - Maturation of neural stem cells and integration into hippocampal circuits - a
      functional study in an in situ model of cerebral ischemia.
AB  - The hippocampus is the region of the brain that is most susceptible to ischemic
      lesion because it contains pyramidal neurons that are highly vulnerable to
      ischemic cell death. A restricted brain neurogenesis limits the possibility of
      reversing massive cell death after stroke and, hence, endorses cell-based
      therapies for neuronal replacement strategies following cerebral ischemia.
      Neurons differentiated from neural stem/progenitor cells (NSPCs) can mature and
      integrate into host circuitry, improving recovery after stroke. However, how the
      host environment regulates the NSPC behavior in post-ischemic tissue remains
      unknown. Here, we studied functional maturation of NSPCs in control and post
      ischemic hippocampal tissue after modelling cerebral ischemia in situ We traced
      the maturation of electrophysiological properties and integration of the NSPC
      derived neurons into the host circuits, with these cells developing appropriate
      activity 3 weeks or less after engraftment. In the tissue subjected to ischemia,
      the NSPC-derived neurons exhibited functional deficits, and differentiation of
      embryonic NSPCs to glial types - oligodendrocytes and astrocytes - was boosted.
      Our findings of the delayed neuronal maturation in post-ischemic conditions,
      while the NSPC differentiation was promoted towards glial cell types, provide new
      insights that could be applicable to stem cell therapy replacement strategies
      used after cerebral ischemia.

PMID- 29361549
TI  - Inflachromene inhibits autophagy through modulation of Beclin 1 activity.
AB  - Autophagy is a central intracellular catabolic mechanism that mediates the
      degradation of cytoplasmic proteins and organelles, and regulation of autophagy
      is essential for homeostasis. HMGB1 is an important sepsis mediator when secreted
      and also functions as an inducer of autophagy by binding to Beclin 1. In this
      study, we studied the effect of inflachromene (ICM), a novel HMGB1 secretion
      inhibitor, on autophagy. ICM inhibited autophagy by inhibiting nucleocytoplasmic
      translocation of HMGB1 and by increasing Beclin 1 ubiquitylation for degradation
      by enhancing the interaction between Beclin 1 and E3 ubiquitin ligase RNF216.
      These data suggest that ICM could be used as a potential autophagy suppressor.

PMID- 29361550
TI  - The developing Drosophila eye - a new model to study centriole reduction.
AB  - In the developing Drosophila eye, the centrioles of the differentiating retinal
      cells are not surrounded by the microtubule-nucleating gamma-tubulin, suggesting
      that they are unable to organize functional microtubule-organizing centers.
      Consistent with this idea, Cnn and Spd-2, which are involved in gamma-tubulin
      recruitment, and the scaffold protein Plp, which plays a role in the organization
      of the pericentriolar material, are lost in the third-instar larval stage.
      However, the centrioles maintain their structural integrity, and both the parent
      centrioles accumulate Asl and Ana1. Although the loading of Asl points to the
      acquisition of the motherhood condition, the daughter centrioles fail to recruit
      Plk4 and do not duplicate. However, it is surprising that the mother centrioles
      that accumulate Plk4 also never duplicate. This suggests that the loading of Plk4
      is not sufficient, in this system, to allow centriole duplication. By halfway
      through pupal life, the centriole number decreases and structural defects,
      ranging from being incomplete or lacking B-tubules, are detected. Asl, Ana1 and
      Sas-4 are still present, suggesting that the centriole integrity does not depend
      on these proteins.

PMID- 29361551
TI  - Characterization of a novel RP2-OSTF1 interaction and its implication for actin
      remodelling.
AB  - Retinitis pigmentosa 2 (RP2) is the causative gene for a form of X-linked retinal
      degeneration. RP2 was previously shown to have GTPase-activating protein (GAP)
      activity towards the small GTPase ARL3 via its N-terminus, but the function of
      the C-terminus remains elusive. Here, we report a novel interaction between RP2
      and osteoclast-stimulating factor 1 (OSTF1), an intracellular protein that
      indirectly enhances osteoclast formation and activity and is a negative regulator
      of cell motility. Moreover, this interaction is abolished by a human pathogenic
      mutation in RP2. We utilized a structure-based approach to pinpoint the binding
      interface to a strictly conserved cluster of residues on the surface of RP2 that
      spans both the C- and N-terminal domains of the protein, and which is
      structurally distinct from the ARL3-binding site. In addition, we show that RP2
      is a positive regulator of cell motility in vitro, recruiting OSTF1 to the cell
      membrane and preventing its interaction with the migration regulator Myo1E.

PMID- 29361552
TI  - The Golgi ribbon in mammalian cells negatively regulates autophagy by modulating
      mTOR activity.
AB  - In vertebrates, individual Golgi stacks are joined into a compact ribbon
      structure; however, the relevance of a ribbon structure has been elusive. Here,
      we exploit the finding that the membrane tether of the trans-Golgi network, GCC88
      (encoded by GCC1), regulates the balance between Golgi mini-stacks and the Golgi
      ribbon. Loss of Golgi ribbons in stable cells overexpressing GCC88 resulted in
      compromised mechanistic target of rapamycin (mTOR) signaling and a dramatic
      increase in LC3-II-positive autophagosomes, whereas RNAi-mediated depletion of
      GCC88 restored the Golgi ribbon and reduced autophagy. mTOR was absent from
      dispersed Golgi mini-stacks whereas recruitment of mTOR to lysosomes was
      unaffected. We show that the Golgi ribbon is a site for localization and
      activation of mTOR, a process dependent on the ribbon structure. We demonstrate a
      strict temporal sequence of fragmentation of Golgi ribbon, loss of Golgi mTOR and
      subsequent increased autophagy. Golgi ribbon fragmentation has been reported in
      various neurodegenerative diseases and we demonstrate the potential relevance of
      our findings in neuronal cells using a model of neurodegeneration. Overall, this
      study highlights a role for the Golgi ribbon in pathways central to cellular
      homeostasis.This article has an associated First Person interview with the first
      author of the paper.

PMID- 29361553
TI  - A branching morphogenesis program governs embryonic growth of the thyroid gland.
AB  - The developmental program that regulates thyroid progenitor cell proliferation is
      largely unknown. Here, we show that branching-like morphogenesis is a driving
      force to attain final size of the embryonic thyroid gland in mice. Sox9, a key
      factor in branching organ development, distinguishes Nkx2-1+ cells in the thyroid
      bud from the progenitors that originally form the thyroid placode in anterior
      endoderm. As lobes develop the thyroid primordial tissue branches several
      generations. Sox9 and Fgfr2b are co-expressed distally in the branching
      epithelium prior to folliculogenesis. The thyroid in Fgf10 null mutants has a
      normal shape but is severely hypoplastic. Absence of Fgf10 leads to defective
      branching and disorganized angiofollicular units although Sox9/Fgfr2b expression
      and the ability of cells to differentiate and form nascent follicles are not
      impaired. These findings demonstrate a novel mechanism of thyroid development
      reminiscent of the Fgf10-Sox9 program that characterizes organogenesis in
      classical branching organs, and provide clues to aid understanding of how the
      endocrine thyroid gland once evolved from an exocrine ancestor present in the
      invertebrate endostyle.

PMID- 29361554
TI  - Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and
      differentiation by repression of Shh.
AB  - Gli3 is a Hedgehog (Hh)-responsive transcription factor that can function as a
      transcriptional repressor or activator. We show that Gli3 activity in mouse
      thymic epithelial cells (TECs) promotes positive selection and differentiation
      from CD4+ CD8+ to CD4+ CD8- single-positive (SP4) cells in the fetal thymus and
      that Gli3 represses Shh Constitutive deletion of Gli3, and conditional deletion
      of Gli3 from TECs, reduced differentiation to SP4, whereas conditional deletion
      of Gli3 from thymocytes did not. Conditional deletion of Shh from TECs increased
      differentiation to SP4, and expression of Shh was upregulated in the Gli3
      deficient thymus. Use of a transgenic Hh reporter showed that the Hh pathway was
      active in thymocytes, and increased in the Gli3-deficient fetal thymus.
      Neutralisation of endogenous Hh proteins in the Gli3-/- thymus restored SP4
      differentiation, indicating that Gli3 in TECs promotes SP4 differentiation by
      repression of Shh Transcriptome analysis showed that Hh-mediated transcription
      was increased whereas TCR-mediated transcription was decreased in Gli3-/-
      thymocytes compared with wild type.

PMID- 29361555
TI  - PLAC8, a new marker for human interstitial extravillous trophoblast cells,
      promotes their invasion and migration.
AB  - Proper differentiation of trophoblast cells in the human placenta is a
      prerequisite for a successful pregnancy, and dysregulation of this process may
      lead to malignant pregnancy outcomes, such as preeclampsia. Finding specific
      markers for different types of trophoblast cells is essential for understanding
      trophoblast differentiation. Here, we report that placenta-specific protein 8
      (PLAC8) is specifically expressed in the interstitial extravillous trophoblast
      cells (iEVTs) on the fetomaternal interface. Using model systems, including
      placental villi-decidua co-culture, iEVTs induction by using primary trophoblast
      cells or explants, etc., we found that PLAC8 promotes invasion and migration of
      iEVTs. Mechanistically, time-lapse imaging, GTPase activity assay, co
      immunoprecipitation and RNA-seq studies show that PLAC8 increases the Cdc42 and
      Rac1 activities, and further induces the formation of filopodia at the leading
      edge of the migratory trophoblast cells. More interestingly, PLAC8 is
      significantly upregulated under hypoxia and expression of PLAC8 is higher in
      iEVTs from preeclamptic placentas when compared with those from the normal
      control placentas. Together, PLAC8 is a new marker for iEVTs and plays an
      important role in promoting trophoblast invasion and migration.

PMID- 29361557
TI  - Two distinct mechanisms silence chinmo in Drosophila neuroblasts and
      neuroepithelial cells to limit their self-renewal.
AB  - Whether common principles regulate the self-renewing potential of neural stem
      cells (NSCs) throughout the developing central nervous system is still unclear.
      In the Drosophila ventral nerve cord and central brain, asymmetrically dividing
      NSCs, called neuroblasts (NBs), progress through a series of sequentially
      expressed transcription factors that limits self-renewal by silencing a genetic
      module involving the transcription factor Chinmo. Here, we find that Chinmo also
      promotes neuroepithelium growth in the optic lobe during early larval stages by
      boosting symmetric self-renewing divisions while preventing differentiation.
      Neuroepithelium differentiation in late larvae requires the transcriptional
      silencing of chinmo by ecdysone, the main steroid hormone, therefore allowing
      coordination of neural stem cell self-renewal with organismal growth. In
      contrast, chinmo silencing in NBs is post-transcriptional and does not require
      ecdysone. Thus, during Drosophila development, humoral cues or tissue-intrinsic
      temporal specification programs respectively limit self-renewal in different
      types of neural progenitors through the transcriptional and post-transcriptional
      regulation of the same transcription factor.

PMID- 29361556
TI  - H2A.Z promotes the transcription of MIR156A and MIR156C in Arabidopsis by
      facilitating the deposition of H3K4me3.
AB  - Vegetative phase change in Arabidopsis thaliana is mediated by a decrease in the
      level of MIR156A and MIR156C, resulting in an increase in the expression of their
      targets, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes. Changes in chromatin
      structure are required for the downregulation of MIR156A and MIR156C, but whether
      chromatin structure contributes to their initial elevated expression is unknown.
      We found that mutations in components of the SWR1 complex (ARP6, SEF) and in
      genes encoding H2A.Z (HTA9 and HTA11) reduce the expression of MIR156A and
      MIR156C, and accelerate vegetative phase change, indicating that H2A.Z promotes
      juvenile vegetative identity. However, arp6 and sef did not accelerate the
      temporal decline in miR156, and the downregulation of MIR156A and MIR156C was not
      accompanied by significant change in the level of H2A.Z at these loci. We
      conclude that H2A.Z contributes to the high expression of MIR156A/MIR156C early
      in shoot development, but does not regulate the timing of vegetative phase
      change. Our results also suggest that H2A.Z promotes the expression of
      MIR156A/MIR156C by facilitating the deposition of H3K4me3, rather than by
      decreasing nucleosome occupancy.

PMID- 29361560
TI  - Transient loss of venous integrity during developmental vascular remodeling leads
      to red blood cell extravasation and clearance by lymphatic vessels.
AB  - Maintenance of blood vessel integrity is crucial for vascular homeostasis and is
      mainly controlled at the level of endothelial cell (EC) junctions. Regulation of
      endothelial integrity has largely been investigated in the mature quiescent
      vasculature. Less is known about how integrity is maintained during vascular
      growth and remodeling involving extensive junctional reorganization. Here, we
      show that embryonic mesenteric blood vascular remodeling is associated with a
      transient loss of venous integrity and concomitant extravasation of red blood
      cells (RBCs), followed by their clearance by the developing lymphatic vessels. In
      wild-type mouse embryos, we observed activated platelets extending filopodia at
      sites of inter-EC gaps. In contrast, embryos lacking the activatory C-type lectin
      domain family 1, member b (CLEC1B) showed extravascular platelets and an
      excessive number of RBCs associated with and engulfed by the first lymphatic EC
      clusters that subsequently form lumenized blood-filled vessels connecting to the
      lymphatic system. These results uncover novel functions of platelets in
      maintaining venous integrity and lymphatic vessels in clearing extravascular RBCs
      during developmental remodeling of the mesenteric vasculature. They further
      provide insight into how vascular abnormalities characterized by blood-filled
      lymphatic vessels arise.

PMID- 29361558
TI  - RBX2 maintains final retinal cell position in a DAB1-dependent and -independent
      fashion.
AB  - The laminated structure of the retina is fundamental for the organization of the
      synaptic circuitry that translates light input into patterns of action
      potentials. However, the molecular mechanisms underlying cell migration and
      layering of the retina are poorly understood. Here, we show that RBX2, a core
      component of the E3 ubiquitin ligase CRL5, is essential for retinal layering and
      function. RBX2 regulates the final cell position of rod bipolar cells, cone
      photoreceptors and Muller glia. Our data indicate that sustained RELN/DAB1
      signaling, triggered by depletion of RBX2 or SOCS7 - a CRL5 substrate adaptor
      known to recruit DAB1 - causes rod bipolar cell misposition. Moreover, whereas
      SOCS7 also controls Muller glia cell lamination, it is not responsible for cone
      photoreceptor positioning, suggesting that RBX2, most likely through CRL5
      activity, controls other signaling pathways required for proper cone
      localization. Furthermore, RBX2 depletion reduces the number of ribbon synapses
      and disrupts cone photoreceptor function. Together, these results uncover RBX2 as
      a crucial molecular regulator of retina morphogenesis and cone photoreceptor
      function.

PMID- 29361561
TI  - Mms19 is a mitotic gene that permits Cdk7 to be fully active as a Cdk-activating
      kinase.
AB  - Mms19 encodes a cytosolic iron-sulphur assembly component. We found that
      Drosophila Mms19 is also essential for mitotic divisions and for the
      proliferation of diploid cells. Reduced Mms19 activity causes severe mitotic
      defects in spindle dynamics and chromosome segregation, and loss of zygotic Mms19
      prevents the formation of imaginal discs. The lack of mitotic tissue in Mms19P/P
      larvae can be rescued by overexpression of the Cdk-activating kinase (CAK)
      complex, an activator of mitotic Cdk1, suggesting that Mms19 functions in mitosis
      to allow CAK (Cdk7/Cyclin H/Mat1) to become fully active as a Cdk1-activating
      kinase. When bound to Xpd and TFIIH, the CAK subunit Cdk7 phosphorylates
      transcriptional targets and not cell cycle Cdks. In contrast, free CAK
      phosphorylates and activates Cdk1. Physical and genetic interaction studies
      between Mms19 and Xpd suggest that their interaction prevents Xpd from binding to
      the CAK complex. Xpd bound to Mms19 therefore frees CAK complexes, allowing them
      to phosphorylate Cdk1 and facilitating progression to metaphase. The structural
      basis for the competitive interaction with Xpd seems to be the binding of Mms19,
      core TFIIH and CAK to neighbouring or overlapping regions of Xpd.

PMID- 29361559
TI  - Comparative analysis of mouse and human placentae across gestation reveals
      species-specific regulators of placental development.
AB  - An increasing body of evidence points to significant spatio-temporal differences
      in early placental development between mouse and human, but a detailed comparison
      of placentae in these two species is missing. We set out to compare placentae
      from both species across gestation, with a focus on trophoblast progenitor
      markers. We found that CDX2 and ELF5, but not EOMES, are expressed in early post
      implantation trophoblast subpopulations in both species. Genome-wide expression
      profiling of mouse and human placentae revealed clusters of genes with distinct
      co-expression patterns across gestation. Overall, there was a closer fit between
      patterns observed in the placentae when the inter-species comparison was
      restricted to human placentae through gestational week 16 (thus, excluding full
      term samples), suggesting that the developmental timeline in mouse runs parallel
      to the first half of human placental development. In addition, we identified
      VGLL1 as a human-specific marker of proliferative cytotrophoblast, where it is co
      expressed with the transcription factor TEAD4. As TEAD4 is involved in
      trophectoderm specification in the mouse, we posit a regulatory role for VGLL1 in
      early events during human placental development.

PMID- 29361563
TI  - Floral homeotic proteins modulate the genetic program for leaf development to
      suppress trichome formation in flowers.
AB  - As originally proposed by Goethe in 1790, floral organs are derived from leaf
      like structures. The conversion of leaves into different types of floral organ is
      mediated by floral homeotic proteins, which, as described by the ABCE model of
      flower development, act in a combinatorial manner. However, how these
      transcription factors bring about this transformation process is not well
      understood. We have previously shown that floral homeotic proteins are involved
      in suppressing the formation of branched trichomes, a hallmark of leaf
      development, on reproductive floral organs of Arabidopsis Here, we present
      evidence that the activities of the C function gene AGAMOUS (AG) and the related
      SHATTERPROOF1/2 genes are superimposed onto the regulatory network that controls
      the distribution of trichome formation in an age-dependent manner. We show that
      AG regulates cytokinin responses and genetically interacts with the organ
      polarity gene KANADI1 to suppress trichome initiation on gynoecia. Thus, our
      results show that parts of the genetic program for leaf development remain active
      during flower formation but have been partially rewired through the activities of
      the floral homeotic proteins.

PMID- 29361562
TI  - The Drosophila Ret gene functions in the stomatogastric nervous system with the
      Maverick TGFbeta ligand and the Gfrl co-receptor.
AB  - The RET receptor tyrosine kinase is crucial for the development of the enteric
      nervous system (ENS), acting as a receptor for Glial cell line-derived
      neurotrophic factor (GDNF) via GFR co-receptors. Drosophila has a well-conserved
      RET homolog (Ret) that has been proposed to function independently of the Gfr
      like co-receptor (Gfrl). We find that Ret is required for development of the
      stomatogastric (enteric) nervous system in both embryos and larvae, and its loss
      results in feeding defects. Live imaging analysis suggests that peristaltic waves
      are initiated but not propagated in mutant midguts. Examination of axons
      innervating the midgut reveals increased branching but the area covered by the
      branches is decreased. This phenotype can be rescued by Ret expression.
      Additionally, Gfrl shares the same ENS and feeding defects, suggesting that Ret
      and Gfrl might function together via a common ligand. We identified the TGFbeta
      family member Maverick (Mav) as a ligand for Gfrl and a Mav chromosomal
      deficiency displayed similar embryonic ENS defects. Our results suggest that the
      Ret and Gfrl families co-evolved before the separation of invertebrate and
      vertebrate lineages.

PMID- 29361564
TI  - ELMO and Sponge specify subapical restriction of Canoe and formation of the
      subapical domain in early Drosophila embryos.
AB  - Canoe/Afadin and the GTPase Rap1 specify the subapical domain during
      cellularization in Drosophila embryos. The timing of domain formation is unclear.
      The subapical domain might gradually mature or emerge synchronously with the
      basal and lateral domains. The potential mechanism for activation of Rap1 by
      guanyl nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs) is
      unknown. Here, we retraced the emergence of the subapical domain at the onset of
      cellularization by in vivo imaging with CanoeYFP in comparison to the lateral and
      basal markers ScribbledGFP and CherrySlam. CanoeYFP accumulates at a subapical
      position at about the same time as the lateral marker ScribbledGFP but a few
      minutes prior to basal CherrySlam. Furthermore, we show that the unconventional
      GEF complex ELMO-Sponge is subapically enriched and is required for subapical
      restriction of Canoe. The localization dynamics of ELMO-Sponge suggests a
      patterning mechanism for positioning the subapical region adjacent to the apical
      region. While marking the disc-like apical regions before cellularization, ELMO
      Sponge redistributes to a ring-like pattern surrounding the apical region at the
      onset of cellularization.

PMID- 29361565
TI  - Rap1 acts via multiple mechanisms to position Canoe and adherens junctions and
      mediate apical-basal polarity establishment.
AB  - Epithelial apical-basal polarity drives assembly and function of most animal
      tissues. Polarity initiation requires cell-cell adherens junction assembly at the
      apical-basolateral boundary. Defining the mechanisms underlying polarity
      establishment remains a key issue. Drosophila embryos provide an ideal model, as
      6000 polarized cells assemble simultaneously. Current data place the actin
      junctional linker Canoe (fly homolog of Afadin) at the top of the polarity
      hierarchy, where it directs Bazooka/Par3 and adherens junction positioning. Here
      we define mechanisms regulating Canoe localization/function. Spatial organization
      of Canoe is multifaceted, involving membrane localization, recruitment to nascent
      junctions and macromolecular assembly at tricellular junctions. Our data suggest
      apical activation of the small GTPase Rap1 regulates all three events, but
      support multiple modes of regulation. The Rap1GEF Dizzy (PDZ-GEF) is crucial for
      Canoe tricellular junction enrichment but not apical retention. The Rap1
      interacting RA domains of Canoe mediate adherens junction and tricellular
      junction recruitment but are dispensable for membrane localization. Our data also
      support a role for Canoe multimerization. These multifactorial inputs shape Canoe
      localization, correct Bazooka and adherens junction positioning, and thus apical
      basal polarity. We integrate the existing data into a new polarity establishment
      model.

PMID- 29361566
TI  - Runx1 is sufficient for blood cell formation from non-hemogenic endothelial cells
      in vivo only during early embryogenesis.
AB  - Hematopoietic cells differentiate during embryogenesis from a population of
      endothelial cells called hemogenic endothelium (HE) in a process called the
      endothelial-to-hematopoietic transition (EHT). The transcription factor Runx1 is
      required for EHT, but for how long and which endothelial cells are competent to
      respond to Runx1 are not known. Here, we show that the ability of Runx1 to induce
      EHT in non-hemogenic endothelial cells depends on the anatomical location of the
      cell and the developmental age of the conceptus. Ectopic expression of Runx1 in
      non-hemogenic endothelial cells between embryonic day (E) 7.5 and E8.5 promoted
      the formation of erythro-myeloid progenitors (EMPs) specifically in the yolk sac,
      the dorsal aorta and the heart. The increase in EMPs was accompanied by a higher
      frequency of HE cells able to differentiate into EMPs in vitro Expression of
      Runx1 just 1 day later (E8.5-E9.5) failed to induce the ectopic formation of
      EMPs. Therefore, endothelial cells, located in specific sites in the conceptus,
      have a short developmental window of competency during which they can respond to
      Runx1 and differentiate into blood cells.

PMID- 29361567
TI  - Drosophila Sidekick is required in developing photoreceptors to enable visual
      motion detection.
AB  - The assembly of functional neuronal circuits requires growth cones to extend in
      defined directions and recognize the correct synaptic partners. Homophilic
      adhesion between vertebrate Sidekick proteins promotes synapse formation between
      retinal neurons involved in visual motion detection. We show here that Drosophila
      Sidekick accumulates in specific synaptic layers of the developing motion
      detection circuit and is necessary for normal optomotor behavior. Sidekick is
      required in photoreceptors, but not in their target lamina neurons, to promote
      the alignment of lamina neurons into columns and subsequent sorting of
      photoreceptor axons into synaptic modules based on their precise spatial
      orientation. Sidekick is also localized to the dendrites of the direction
      selective T4 and T5 cells, and is expressed in some of their presynaptic
      partners. In contrast to its vertebrate homologs, Sidekick is not essential for
      T4 and T5 to direct their dendrites to the appropriate layers or to receive
      synaptic contacts. These results illustrate a conserved requirement for Sidekick
      proteins in establishing visual motion detection circuits that is achieved
      through distinct cellular mechanisms in Drosophila and vertebrates.

PMID- 29361568
TI  - Integrated analysis of single-cell embryo data yields a unified transcriptome
      signature for the human pre-implantation epiblast.
AB  - Single-cell profiling techniques create opportunities to delineate cell fate
      progression in mammalian development. Recent studies have provided transcriptome
      data from human pre-implantation embryos, in total comprising nearly 2000
      individual cells. Interpretation of these data is confounded by biological
      factors, such as variable embryo staging and cell-type ambiguity, as well as
      technical challenges in the collective analysis of datasets produced with
      different sample preparation and sequencing protocols. Here, we address these
      issues to assemble a complete gene expression time course spanning human pre
      implantation embryogenesis. We identify key transcriptional features over
      developmental time and elucidate lineage-specific regulatory networks. We resolve
      post-hoc cell-type assignment in the blastocyst, and define robust
      transcriptional prototypes that capture epiblast and primitive endoderm lineages.
      Examination of human pluripotent stem cell transcriptomes in this framework
      identifies culture conditions that sustain a naive state pertaining to the inner
      cell mass. Our approach thus clarifies understanding both of lineage segregation
      in the early human embryo and of in vitro stem cell identity, and provides an
      analytical resource for comparative molecular embryology.

PMID- 29361569
TI  - Wnt6 maintains anterior escort cells as an integral component of the germline
      stem cell niche.
AB  - Stem cells reside in a niche, a local environment whose cellular and molecular
      complexity is still being elucidated. In Drosophila ovaries, germline stem cells
      depend on cap cells for self-renewing signals and physical attachment. Germline
      stem cells also contact the anterior escort cells, and here we report that
      anterior escort cells are absolutely required for germline stem cell maintenance.
      When escort cells die from impaired Wnt signaling or hid expression, the loss of
      anterior escort cells causes loss of germline stem cells. Anterior escort cells
      function as an integral niche component by promoting DE-cadherin anchorage and by
      transiently expressing the Dpp ligand to promote full-strength BMP signaling in
      germline stem cells. Anterior escort cells are maintained by Wnt6 ligands
      produced by cap cells; without Wnt6 signaling, anterior escort cells die leaving
      vacancies in the niche, leading to loss of germline stem cells. Our data identify
      anterior escort cells as constituents of the germline stem cell niche, maintained
      by a cap cell-produced Wnt6 survival signal.

PMID- 29361570
TI  - Dissection of genetic regulation of compound inflorescence development in
      Medicago truncatula.
AB  - Development of inflorescence architecture is controlled by genetic regulatory
      networks. TERMINAL FLOWER1 (TFL1), APETALA1 (AP1), LEAFY (LFY) and FRUITFULL
      (FUL) are core regulators for inflorescence development. To understand the
      regulation of compound inflorescence development, we characterized mutants of
      corresponding orthologous genes, MtTFL1, MtAP1, SINGLE LEAFLET1 (SGL1) and
      MtFULc, in Medicago truncatula, and analyzed expression patterns of these genes.
      Results indicate that MtTFL1, MtFULc, MtAP1 and SGL1 play specific roles in
      identity determination of primary inflorescence meristems, secondary
      inflorescence meristems, floral meristems and common primordia, respectively.
      Double mutation of MtTFL1 and MtFULc transforms compound inflorescences to simple
      flowers, whereas single mutation of MtTFL1 changes the inflorescence branching
      pattern from monopodial to sympodial. Double mutant mtap1sgl1 completely loses
      floral meristem identity. We conclude that inflorescence architecture in M.
      truncatula is controlled by spatiotemporal expression of MtTFL1, MtFULc, MtAP1
      and SGL1 through reciprocal repression. Although this regulatory network shares
      similarity with the pea model, it has specificity in regulating inflorescence
      architecture in Mtruncatula This study establishes M. truncatula as an excellent
      genetic model for understanding compound inflorescence development in related
      legume crops.

PMID- 29361571
TI  - Stereotypical architecture of the stem cell niche is spatiotemporally established
      by miR-125-dependent coordination of Notch and steroid signaling.
AB  - Stem cell niches act as signaling platforms that regulate stem cell self-renewal
      and sustain stem cells throughout life; however, the specific developmental
      events controlling their assembly are not well understood. Here, we show that
      during Drosophila ovarian germline stem cell niche formation, the status of Notch
      signaling in the cell can be reprogrammed. This is controlled via steroid-induced
      miR-125, which targets a negative regulator of Notch signaling, Tom. Thus, miR
      125 acts as a spatiotemporal coordinator between paracrine Notch and endocrine
      steroid signaling. Moreover, a dual security mechanism for Notch signaling
      activation exists to ensure the robustness of niche assembly. Particularly, stem
      cell niche cells can be specified either via lateral inhibition, in which a niche
      cell precursor acquires Notch signal-sending status randomly, or via peripheral
      induction, whereby Delta is produced by a specific cell. When one mechanism is
      perturbed due to mutations, developmental defects or environmental stress, the
      remaining mechanism ensures that the niche is formed, perhaps abnormally, but
      still functional. This guarantees that the germline stem cells will have their
      residence, thereby securing progressive oogenesis and, thus, organism
      reproduction.

PMID- 29361572
TI  - Continuous root xylem formation and vascular acclimation to water deficit
      involves endodermal ABA signalling via miR165.
AB  - The plant root xylem comprises a specialized tissue for water distribution to the
      shoot. Despite its importance, its potential morphological plasticity in response
      to environmental conditions such as limited water availability has not been
      thoroughly studied. Here, we identify a role for the phytohormone abscisic acid
      (ABA) for proper xylem development and describe how ABA signalling-mediated
      effects on core developmental regulators are employed to alter xylem morphology
      under limited water availability in Arabidopsis Plants with impaired ABA
      biosynthesis and reduced ABA signalling in the cell layer surrounding the
      vasculature displayed defects in xylem continuity, suggesting that non-cell
      autonomous ABA signalling is required for proper xylem development. Conversely,
      upon external ABA application or under limited water availability, extra xylem
      strands were formed. The observed xylem developmental alterations were dependent
      on adequate endodermal ABA signalling, which activated MIR165A. This resulted in
      increased miR165 levels that repress class III HD-ZIP transcription factors in
      the stele. We conclude that a pathway known to control core developmental
      features is employed as a means of modifying plant xylem morphology under
      conditions of environmental stress.

PMID- 29361573
TI  - Podoplanin regulates mammary stem cell function and tumorigenesis by potentiating
      Wnt/beta-catenin signaling.
AB  - Stem cells (SCs) drive mammary development, giving rise postnatally to an
      epithelial bilayer composed of luminal and basal myoepithelial cells.
      Dysregulation of SCs is thought to be at the origin of certain breast cancers;
      however, the molecular identity of SCs and the factors regulating their function
      remain poorly defined. We identified the transmembrane protein podoplanin (Pdpn)
      as a specific marker of the basal compartment, including multipotent SCs, and
      found Pdpn localized at the basal-luminal interface. Embryonic deletion of Pdpn
      targeted to basal cells diminished basal and luminal SC activity and affected the
      expression of several Wnt/beta-catenin signaling components in basal cells.
      Moreover, Pdpn loss attenuated mammary tumor formation in a mouse model of beta
      catenin-induced breast cancer, limiting tumor-initiating cell expansion and
      promoting molecular features associated with mesenchymal-to-epithelial cell
      transition. In line with the loss-of-function data, we demonstrated that
      mechanistically Pdpn enhances Wnt/beta-catenin signaling in mammary basal cells.
      Overall, this study uncovers a role for Pdpn in mammary SC function and,
      importantly, identifies Pdpn as a new regulator of Wnt/beta-catenin signaling, a
      key pathway in mammary development and tumorigenesis.

PMID- 29361574
TI  - TCF7L1 suppresses primitive streak gene expression to support human embryonic
      stem cell pluripotency.
AB  - Human embryonic stem cells (hESCs) are exquisitely sensitive to WNT ligands,
      which rapidly cause differentiation. Therefore, hESC self-renewal requires robust
      mechanisms to keep the cells in a WNT inactive but responsive state. How they
      achieve this is largely unknown. We explored the role of transcriptional
      regulators of WNT signaling, the TCF/LEFs. As in mouse ESCs, TCF7L1 is the
      predominant family member expressed in hESCs. Genome-wide, it binds a gene cohort
      involved in primitive streak formation at gastrulation, including NODAL, BMP4 and
      WNT3 Comparing TCF7L1-bound sites with those bound by the WNT signaling effector
      beta-catenin indicates that TCF7L1 acts largely on the WNT signaling pathway.
      TCF7L1 overlaps less with the pluripotency regulators OCT4 and NANOG than in
      mouse ESCs. Gain- and loss-of-function studies indicate that TCF7L1 suppresses
      gene cohorts expressed in the primitive streak. Interestingly, we find that BMP4,
      another driver of hESC differentiation, downregulates TCF7L1, providing a
      mechanism of BMP and WNT pathway intersection. Together, our studies indicate
      that TCF7L1 plays a major role in maintaining hESC pluripotency, which has
      implications for human development during gastrulation.

PMID- 29361576
TI  - Ammonia excretion and acid-base regulation in the American horseshoe crab,
      Limulus polyphemus.
AB  - Many studies have investigated ammonia excretion and acid-base regulation in
      aquatic arthropods, yet current knowledge of marine chelicerates is non-existent.
      In American horseshoe crabs (Limulus polyphemus), book gills bear physiologically
      distinct regions: dorsal and ventral half-lamellae, a central mitochondria-rich
      area (CMRA) and peripheral mitochondria-poor areas (PMPAs). In the present study,
      the CMRA and ventral half-lamella exhibited characteristics important for ammonia
      excretion and/or acid-base regulation, as supported by high expression levels of
      Rhesus-protein 1 (LpRh-1), cytoplasmic carbonic anhydrase (CA-2) and
      hyperpolarization-activated cyclic nucleotide-gated K+ channel (HCN) compared
      with the PMPA and dorsal half-lamella. The half-lamellae displayed remarkable
      differences; the ventral epithelium was ion-leaky whereas the dorsal counterpart
      possessed an exceptionally tight epithelium. LpRh-1 was more abundant than Rhesus
      protein 2 (LpRh-2) in all investigated tissues, but LpRh-2 was more prevalent in
      the PMPA than in the CMRA. Ammonia influx associated with high ambient ammonia
      (HAA) treatment was counteracted by intact animals and complemented by
      upregulation of branchial CA-2, V-type H+-ATPase (HAT), HCN and LpRh-1 mRNA
      expression. The dorsal epithelium demonstrated characteristics of active ammonia
      excretion. However, an influx was observed across the ventral epithelium as a
      result of the tissue's high ion conductance, although the influx rate was not
      proportionately high considering the ~3-fold inwardly directed ammonia gradient.
      These novel findings suggest a role for the coxal gland in excretion and in the
      maintenance of hemolymph ammonia regulation under HAA. Hypercapnic exposure
      induced compensatory respiratory acidosis and partial metabolic depression.
      Functional differences between the two halves of a branchial lamella may be
      physiologically beneficial in reducing the backflow of waste products into
      adjacent lamellae, especially in fluctuating environments where ammonia levels
      can increase.

PMID- 29361577
TI  - Nosema ceranae parasitism impacts olfactory learning and memory and
      neurochemistry in honey bees (Apis mellifera).
AB  - Nosema sp. is an internal parasite of the honey bee, Apis mellifera, and one of
      the leading contributors to colony losses worldwide. This parasite is found in
      the honey bee midgut and has profound consequences for the host's physiology.
      Nosema sp. impairs foraging performance in honey bees, yet, it is unclear whether
      this parasite affects the bee's neurobiology. In this study, we examined whether
      Nosema sp. affects odor learning and memory and whether the brains of parasitized
      bees show differences in amino acids and biogenic amines. We took newly emerged
      bees and fed them with Nosema ceranae At approximate nurse and forager ages, we
      employed an odor-associative conditioning assay using the proboscis extension
      reflex and two bioanalytical techniques to measure changes in brain chemistry. We
      found that nurse-aged bees infected with N. ceranae significantly outperformed
      controls in odor learning and memory, suggestive of precocious foraging, but by
      forager age, infected bees showed deficits in learning and memory. We also
      detected significant differences in amino acid concentrations, some of which were
      age specific, as well as altered serotonin, octopamine, dopamine and l-dopa
      concentrations in the brains of parasitized bees. These findings suggest that N.
      ceranae infection affects honey bee neurobiology and may compromise behavioral
      tasks. These results yield new insight into the host-parasite dynamic of honey
      bees and N. ceranae, as well as the neurochemistry of odor learning and memory
      under normal and parasitic conditions.

PMID- 29361575
TI  - Nkx genes establish second heart field cardiomyocyte progenitors at the arterial
      pole and pattern the venous pole through Isl1 repression.
AB  - NKX2-5 is the most commonly mutated gene associated with human congenital heart
      defects (CHDs), with a predilection for cardiac pole abnormalities. This
      homeodomain transcription factor is a central regulator of cardiac development
      and is expressed in both the first and second heart fields (FHF and SHF). We have
      previously revealed essential functions of nkx2.5 and nkx2.7, two Nkx2-5 homologs
      expressed in zebrafish cardiomyocytes, in maintaining ventricular identity.
      However, the differential roles of these genes in the specific subpopulations of
      the anterior (aSHF) and posterior (pSHF) SHFs have yet to be fully defined. Here,
      we show that Nkx genes regulate aSHF and pSHF progenitors through independent
      mechanisms. We demonstrate that Nkx genes restrict proliferation of aSHF
      progenitors in the outflow tract, delimit the number of pSHF progenitors at the
      venous pole and pattern the sinoatrial node acting through Isl1 repression.
      Moreover, optical mapping highlights the requirement for Nkx gene dose in
      establishing electrophysiological chamber identity and in integrating the
      physiological connectivity of FHF and SHF cardiomyocytes. Ultimately, our results
      may shed light on the discrete errors responsible for NKX2-5-dependent human CHDs
      of the cardiac outflow and inflow tracts.

PMID- 29361579
TI  - Negligible differences in metabolism and thermal tolerance between diploid and
      triploid Atlantic salmon (Salmo salar).
AB  - The mechanisms that underlie thermal tolerance in aquatic ectotherms remain
      unresolved. Triploid fish have been reported to exhibit lower thermal tolerance
      than diploids, offering a potential model organism to better understand the
      physiological drivers of thermal tolerance. Here, we compared triploid and
      diploid juvenile Atlantic salmon (Salmo salar) in freshwater to investigate the
      proposed link between aerobic capacity and thermal tolerance. We measured
      specific growth rates (SGR) and resting (aerobic) metabolic rates (RMR) in
      freshwater at 3, 7 and 9 weeks of acclimation to 10, 14 and 18 degrees C.
      Additionally, maximum metabolic rates (MMR) were measured at 3 and 7 weeks of
      acclimation, and critical thermal maxima (CTmax) were measured at 9 weeks. Mass,
      SGR and RMR differed between ploidies across all temperatures at the beginning of
      the acclimation period, but all three metrics were similar across ploidies by
      week 7. Aerobic scope (MMR-RMR) remained consistent across ploidies, acclimation
      temperatures and time. At 9 weeks, CTmax was independent of ploidy, but
      correlated positively with acclimation temperature despite the similar aerobic
      scope between acclimation groups. Our findings suggest that acute thermal
      tolerance is not modulated by aerobic scope, and the altered genome of triploid
      Atlantic salmon does not translate to reduced thermal tolerance of juvenile fish
      in freshwater.

PMID- 29361580
TI  - Fitness consequences of plasticity in an extended phenotype.
AB  - Like regular phenotypes, extended phenotypes have demonstrable fitness advantages
      and their properties may vary plastically across environments. However, the
      fitness advantages of plasticity are only known for a select few extended
      phenotypes. It is known that the form and functions of spider orb webs can be
      manipulated by laboratory experiments. For instance, the physical and chemical
      properties of the spiral and gluey silks vary in property as protein intake
      varies. Orb web spiders thus represent good models for extended phenotypic
      plasticity studies. We performed experiments manipulating the protein intake of
      two vertically aligned orb web building spiders to determine whether variations
      in the chemical and physical properties of their spiral and gluey silk affect
      prey retention in their webs. We found in both spider species that individuals
      deprived of protein had a greater gluey silk glycoprotein core volume, and this
      correlated strongly with spiral thread stickiness and increased prey retention by
      the webs. Moreover, we found strong positive correlations between glue droplet
      volume and glycoprotein core volume for spiders in the protein-deprived
      treatment, but weaker correlations for protein-fed spiders. We interpreted these
      findings as the spiders investing more in glycoprotein when nutrient deprived. We
      attribute the associated increase in prey retention capacity as a fitness
      consequence of plasticity in the spiral properties.

PMID- 29361578
TI  - The loss of hemoglobin and myoglobin does not minimize oxidative stress in
      Antarctic icefishes.
AB  - The unusual pattern of expression of hemoglobin (Hb) and myoglobin (Mb) among
      Antarctic notothenioid fishes provides an exceptional model system for assessing
      the impact of these proteins on oxidative stress. We tested the hypothesis that
      the lack of oxygen-binding proteins may reduce oxidative stress. Levels and
      activity of pro-oxidants and small-molecule and enzymatic antioxidants, and
      levels of oxidized lipids and proteins in the liver, oxidative skeletal muscle
      and heart ventricle were quantified in five species of notothenioid fishes
      differing in the expression of Hb and Mb. Levels of ubiquitinated proteins and
      rates of protein degradation by the 20S proteasome were also quantified. Although
      levels of oxidized proteins and lipids, ubiquitinated proteins, and antioxidants
      were higher in red-blooded fishes than in Hb-less icefishes in some tissues, this
      pattern did not persist across all tissues. Expression of Mb was not associated
      with oxidative damage in the heart ventricle, whereas the activity of citrate
      synthase and the contents of heme were positively correlated with oxidative
      damage in most tissues. Despite some tissue differences in levels of protein
      carbonyls among species, rates of degradation by the 20S proteasome were not
      markedly different, suggesting either alternative pathways for eliminating
      oxidized proteins or that redox tone varies among species. Together, our data
      indicate that the loss of Hb and Mb does not correspond with a clear pattern of
      either reduced oxidative defense or oxidative damage.

PMID- 29361581
TI  - Myosin phosphorylation improves contractile economy of mouse fast skeletal muscle
      during staircase potentiation.
AB  - Phosphorylation of the myosin regulatory light chain (RLC) by skeletal myosin
      light chain kinase (skMLCK) potentiates rodent fast twitch muscle but is an ATP
      requiring process. Our objective was to investigate the effect of skMLCK
      catalyzed RLC phosphorylation on the energetic cost of contraction and the
      contractile economy (ratio of mechanical output to metabolic input) of mouse fast
      twitch muscle in vitro (25 degrees C). To this end, extensor digitorum longus
      (EDL) muscles from wild-type (WT) and from skMLCK-devoid (skMLCK-/-) mice were
      subjected to repetitive low-frequency stimulation (10 Hz for 15 s) to produce
      staircase potentiation of isometric twitch force, after which muscles were quick
      frozen for determination of high-energy phosphate consumption (HEPC). During
      stimulation, WT muscles displayed significant potentiation of isometric twitch
      force while skMLCK-/- muscles did not (i.e. 23% versus 5% change, respectively).
      Consistent with this, RLC phosphorylation was increased ~3.5-fold from the
      unstimulated control value in WT but not in skMLCK-/- muscles. Despite these
      differences, the HEPC of WT muscles was not greater than that of skMLCK-/-
      muscles. As a result of the increased contractile output relative to HEPC, the
      calculated contractile economy of WT muscles was greater than that of skMLCK-/-
      muscles. Thus, our results suggest that skMLCK-catalyzed phosphorylation of the
      myosin RLC increases the contractile economy of WT mouse EDL muscle compared with
      skMLCK-/- muscles without RLC phosphorylation.

PMID- 29361582
TI  - Auditory neural networks involved in attention modulation prefer biologically
      significant sounds and exhibit sexual dimorphism in anurans.
AB  - Allocating attention to biologically relevant stimuli in a complex environment is
      critically important for survival and reproductive success. In humans, attention
      modulation is regulated by the frontal cortex, and is often reflected by changes
      in specific components of the event-related potential (ERP). Although brain
      networks for attention modulation have been widely studied in primates and avian
      species, little is known about attention modulation in amphibians. The present
      study aimed to investigate the attention modulation networks in an anuran
      species, the Emei music frog (Babina daunchina). Male music frogs produce
      advertisement calls from within underground nest burrows that modify the acoustic
      features of the calls, and both males and females prefer calls produced from
      inside burrows. We broadcast call stimuli to male and female music frogs while
      simultaneously recording electroencephalographic (EEG) signals from the
      telencephalon and mesencephalon. Granger causal connectivity analysis was used to
      elucidate functional brain networks within the time window of ERP components. The
      results show that calls produced from inside nests which are highly sexually
      attractive result in the strongest brain connections; both ascending and
      descending connections involving the left telencephalon were stronger in males
      while those in females were stronger with the right telencephalon. Our findings
      indicate that the frog brain allocates neural attention resources to highly
      attractive sounds within the window of early components of ERP, and that such
      processing is sexually dimorphic, presumably reflecting the different
      reproductive strategies of males and females.

PMID- 29361583
TI  - Oxidation of linoleic and palmitic acid in pre-hibernating and hibernating common
      noctule bats revealed by 13C breath testing.
AB  - Mammals fuel hibernation by oxidizing saturated and unsaturated fatty acids from
      triacylglycerols in adipocytes, yet the relative importance of these two
      categories as an oxidative fuel may change during hibernation. We studied the
      selective use of fatty acids as an oxidative fuel in noctule bats (Nyctalus
      noctula). Pre-hibernating noctule bats that were fed 13C-enriched linoleic acid
      (LA) showed 12 times higher tracer oxidation rates compared with conspecifics fed
      13C-enriched palmitic acid (PA). After this experiment, we supplemented the diet
      of bats with the same fatty acids on five subsequent days to enrich their fat
      depots with the respective tracer. We then compared the excess 13C enrichment
      (excess atom percentage, APE) in breath of bats for torpor and arousal events
      during early and late hibernation. We observed higher APE values in breath of
      bats fed 13C-enriched LA than in bats fed 13C-enriched PA for both states (torpor
      and arousal), and also for both periods. Thus, hibernating bats selectively
      oxidized endogenous LA instead of PA, probably because of faster transportation
      rates of polyunsaturated fatty acids compared with saturated fatty acids. We did
      not observe changes in APE values in the breath of torpid animals between early
      and late hibernation. Skin temperature of torpid animals increased by 0.7 degrees
      C between early and late hibernation in bats fed PA, whereas it decreased by -0.8
      degrees C in bats fed LA, highlighting that endogenous LA may fulfil two
      functions when available in excess: serving as an oxidative fuel and supporting
      cell membrane functionality.

PMID- 29361584
TI  - The biomechanics of tree frogs climbing curved surfaces: a gripping problem.
AB  - The adhesive mechanisms of climbing animals have become an important research
      topic because of their biomimetic implications. We examined the climbing
      abilities of hylid tree frogs on vertical cylinders of differing diameter and
      surface roughness to investigate the relative roles of adduction forces
      (gripping) and adhesion. Tree frogs adhere using their toe pads and subarticular
      tubercles, the adhesive joint being fluid-filled. Our hypothesis was that on an
      effectively flat surface (adduction forces on the largest 120 mm diameter
      cylinder were insufficient to allow climbing), adhesion would effectively be the
      only means by which tree frogs could climb, but on the 44 and 13 mm diameter
      cylinders, frogs could additionally utilise adduction forces by gripping the
      cylinder either with their limbs outstretched or by grasping around the cylinder
      with their digits, respectively. The frogs' performance would also depend on
      whether the surfaces were smooth (easy to adhere to) or rough (relatively non
      adhesive). Our findings showed that climbing performance was highest on the
      narrowest smooth cylinder. Frogs climbed faster, frequently using a 'walking
      trot' gait rather than the 'lateral sequence walk' used on other cylinders. Using
      an optical technique to visualise substrate contact during climbing on smooth
      surfaces, we also observed an increasing engagement of the subarticular tubercles
      on the narrower cylinders. Finally, on the rough substrate, frogs were unable to
      climb the largest diameter cylinder, but were able to climb the narrowest one
      slowly. These results support our hypotheses and have relevance for the design of
      climbing robots.

PMID- 29361585
TI  - The reluctant visitor: a terpenoid in toxic nectar can reduce olfactory learning
      and memory in Asian honey bees.
AB  - The nectar of the thunder god vine, Tripterygium hypoglaucum, contains a
      terpenoid, triptolide (TRP), that may be toxic to the sympatric Asian honey bee,
      Apis cerana, because honey produced from this nectar is toxic to bees. However,
      these bees will forage on, recruit for, and pollinate this plant during a
      seasonal dearth of preferred food sources. Olfactory learning plays a key role in
      forager constancy and pollination, and we therefore tested the effects of acute
      and chronic TRP feeding on forager olfactory learning, using proboscis extension
      reflex conditioning. At concentrations of 0.5-10 ug TRP ml-1, there were no
      learning effects of acute exposure. However, memory retention (1 h after the last
      learning trial) significantly decreased by 56% following acute consumption of 0.5
      ug TRP ml-1 Chronic exposure did not alter learning or memory, except at high
      concentrations (5 and 10 ug TRP ml-1). TRP concentrations in nectar may therefore
      not significantly harm plant pollination. Surprisingly, TRP slightly increased
      bee survival, and thus other components in T. hypoglaucum honey may be toxic.
      Long-term exposure to TRP could have colony effects but these may be ameliorated
      by the bees' aversion to T. hypoglaucum nectar when other food sources are
      available and, perhaps, by detoxification mechanisms. The co-evolution of this
      plant and its reluctant visitor may therefore likely illustrate a classic
      compromise between the interests of both actors.

PMID- 29361586
TI  - Femoral bone perfusion through the nutrient foramen during growth and locomotor
      development of western grey kangaroos (Macropus fuliginosus).
AB  - The nutrient artery passes through the nutrient foramen on the shaft of the femur
      and supplies more than half of the total blood flow to the bone. Assuming that
      the size of the nutrient foramen correlates with the size of the nutrient artery,
      an index of blood flow rate (Qi) can be calculated from nutrient foramen
      dimensions. Interspecific Qi is proportional to locomotor activity levels in
      adult mammals, birds and reptiles. However, no studies have yet estimated
      intraspecific Qi to test for the effects of growth and locomotor development on
      bone blood flow requirements. In this study, we used micro-CT and medical CT
      scanning to measure femoral dimensions and foramen radius to calculate femoral Qi
      during the in-pouch and post-pouch life stages of western grey kangaroos
      (Macropus fuliginosus) weighing 5.7 g to 70.5 kg and representing a 12,350-fold
      range in body mass. A biphasic scaling relationship between Qi and body mass was
      observed (breakpoint at ca. 1-5 kg body mass right before permanent pouch exit),
      with a steep exponent of 0.96+/-0.09 (95% CI) during the in-pouch life stage and
      a statistically independent exponent of -0.59+/-0.90 during the post-pouch life
      stage. In-pouch joeys showed Qi values that were 50-100 times higher than those
      of adult diprotodont marsupials of the same body mass, but gradually converged
      with them as post-pouch adults. Bone modelling during growth appears to be the
      main determinant of femoral bone blood flow during in-pouch development, whereas
      bone remodelling for micro-fracture repair due to locomotion gradually becomes
      the main determinant when kangaroos leave the pouch and become more active.

PMID- 29361588
TI  - Immune function and the decision to deploy weapons during fights in the beadlet
      anemone, Actinia equina.
AB  - The ability to mitigate the costs of engaging in a fight will depend on an
      individual's physiological state. However, the experience of fighting itself may,
      in turn, affect an individual's state, especially if the fight results in injury.
      Previous studies have found a correlation between immune state and fighting
      success, but the causal direction of this relationship remains unclear. Does
      immune state determine fighting success? Or does fighting itself influence
      subsequent immune state? Using the beadlet anemone, Actinia equina, we
      disentangled the cause and effect of this relationship, measuring immune response
      once pre-fight and twice post-fight. Contrary to previous findings, pre-fight
      immune response did not predict fighting success, but rather predicted whether an
      individual used its weapons during the fight. Furthermore, weapon use and contest
      outcome significantly affected post-fight immune response. Individuals that used
      their weapons maintained a stable immune response following the fight, whereas
      those that fought non-injuriously did not. Furthermore, although winners suffered
      a reduction in immune response similar to that of losers immediately post-fight,
      winners began to recover pre-fight levels within 24 h. Our findings indicate that
      immune state can influence strategic fighting decisions and, moreover, that fight
      outcome and the agonistic behaviours expressed can significantly affect
      subsequent immunity.

PMID- 29361587
TI  - Biomechanical mechanisms underlying exosuit-induced improvements in walking
      economy after stroke.
AB  - Stroke-induced hemiparetic gait is characteristically asymmetric and
      metabolically expensive. Weakness and impaired control of the paretic ankle
      contribute to reduced forward propulsion and ground clearance - walking subtasks
      critical for safe and efficient locomotion. Targeted gait interventions that
      improve paretic ankle function after stroke are therefore warranted. We have
      developed textile-based, soft wearable robots that transmit mechanical power
      generated by off-board or body-worn actuators to the paretic ankle using Bowden
      cables (soft exosuits) and have demonstrated the exosuits can overcome deficits
      in paretic limb forward propulsion and ground clearance, ultimately reducing the
      metabolic cost of hemiparetic walking. This study elucidates the biomechanical
      mechanisms underlying exosuit-induced reductions in metabolic power. We evaluated
      the relationships between exosuit-induced changes in the body center of mass
      (COM) power generated by each limb, individual joint power and metabolic power.
      Compared with walking with an exosuit unpowered, exosuit assistance produced more
      symmetrical COM power generation during the critical period of the step-to-step
      transition (22.4+/-6.4% more symmetric). Changes in individual limb COM power
      were related to changes in paretic (R2=0.83, P=0.004) and non-paretic (R2=0.73,
      P=0.014) ankle power. Interestingly, despite the exosuit providing direct
      assistance to only the paretic limb, changes in metabolic power were related to
      changes in non-paretic limb COM power (R2=0.80, P=0.007), not paretic limb COM
      power (P>0.05). These findings contribute to a fundamental understanding of how
      individuals post-stroke interact with an exosuit to reduce the metabolic cost of
      hemiparetic walking.

PMID- 29361589
TI  - Cold temperature represses daily rhythms in the liver transcriptome of a
      stenothermal teleost under decreasing day length.
AB  - The climate-change-driven increase in temperature is occurring rapidly and
      decreasing the predictability of seasonal rhythms at high latitudes. It is
      therefore urgent to understand how a change in the relationship between
      photoperiod and temperature can affect ectotherms in these environments. We
      tested whether temperature affects daily rhythms of transcription in a cold
      adapted salmonid using high-throughput RNA sequencing. Arctic char (Salvelinus
      alpinus) from a subarctic population were reared at a high and a low temperature
      (15 and 8 degrees C) for 1 month under natural, decreasing day length during late
      summer. Liver transcriptomes were compared between samples collected in the
      middle and towards the end of the light period and in the middle of the dark
      period. Daily variation in transcription was lower in fish from the low
      temperature compared with strong daily variation in warm-acclimated fish,
      suggesting that cold temperatures dampen the cycling of transcriptional rhythms
      under a simultaneously decreasing day length. Different circadian clock genes had
      divergent expression patterns, responding either by decreased expression or by
      increased rhythmicity at 15 degrees C compared with 8 degrees C. The results
      point out mechanisms that can affect the ability of fish to adapt to increasing
      temperatures caused by climate change.

PMID- 29361590
TI  - Limits to sustained energy intake. XXVII. Trade-offs between first and second
      litters in lactating mice support the ecological context hypothesis.
AB  - Increased reproductive effort may lead to trade-offs with future performance and
      impact offspring, thereby influencing optimal current effort level. We
      experimentally enlarged or reduced litter size in mice during their first
      lactation, and then followed them through a successive unmanipulated lactation.
      Measurements of food intake, body mass, milk energy output (MEO), litter size and
      litter mass were taken. Offspring from the first lactation were also bred to
      investigate their reproductive success. In their first lactation, mothers with
      enlarged litters (n=9, 16 pups) weaned significantly smaller pups, culled more
      pups, and increased MEO and food intake compared with mothers with reduced
      litters (n=9, 5 pups). In the second lactation, no significant differences in pup
      mass or litter size were observed between groups, but mothers that had previously
      reared enlarged litters significantly decreased pup mass, MEO and food intake
      compared with those that had reared reduced litters. Female offspring from
      enlarged litters weaned slightly smaller pups than those from reduced litters,
      but displayed no significant differences in any of the other variables measured.
      These results suggest that females with enlarged litters suffered from a greater
      energetic burden during their first lactation, and this was associated with
      lowered performance in a successive reproductive event and impacted on their
      offspring's reproductive performance. Female 'choice' about how much to invest in
      the first lactation may thus be driven by trade-offs with future reproductive
      success. Hence, the 'limit' on performance may not be a hard physiological limit.
      These data support the ecological context hypothesis.

PMID- 29361591
TI  - Naked mole rat brain mitochondria electron transport system flux and H+ leak are
      reduced during acute hypoxia.
AB  - Mitochondrial respiration and ATP production are compromised by hypoxia. Naked
      mole rats (NMRs) are among the most hypoxia-tolerant mammals and reduce metabolic
      rate in hypoxic environments; however, little is known regarding mitochondrial
      function during in vivo hypoxia exposure in this species. To address this
      knowledge gap, we asked whether the function of NMR brain mitochondria exhibits
      metabolic plasticity during acute hypoxia. Respirometry was utilized to assess
      whole-animal oxygen consumption rates and high-resolution respirometry was
      utilized to assess electron transport system (ETS) function in saponin
      permeabilized NMR brain. We found that NMR whole-animal oxygen consumption rate
      reversibly decreased by ~85% in acute hypoxia (4 h at 3% O2). Similarly, relative
      to untreated controls, permeabilized brain respiratory flux through the ETS was
      decreased by ~90% in acutely hypoxic animals. Relative to carbonyl cyanide p
      trifluoro-methoxyphenylhydrazone-uncoupled total ETS flux, this functional
      decrease was observed equally across all components of the ETS except for complex
      IV (cytochrome c oxidase), at which flux was further reduced, supporting a
      regulatory role for this enzyme during acute hypoxia. The maximum enzymatic
      capacities of ETS complexes I-V were not altered by acute hypoxia; however, the
      mitochondrial H+ gradient decreased in step with the decrease in ETS respiration.
      Taken together, our results indicate that NMR brain ETS flux and H+ leak are
      reduced in a balanced and regulated fashion during acute hypoxia. Changes in NMR
      mitochondrial metabolic plasticity mirror whole-animal metabolic responses to
      hypoxia.

PMID- 29361592
TI  - Stress decreases pollen foraging performance in honeybees.
AB  - Foraging in honeybees is energetically demanding. Here, we examined whether
      stressors, which generally increase metabolic demands, can impair foraging
      performance. A controlled non-pathogenic stressor (immune challenge) resulted in
      a change in the foraging preferences of bees. It reduced pollen foraging and
      increased the duration of trips in pollen foragers. Stress also reduced the
      amount of octopamine in the brain of pollen foragers (a biogenic amine involved
      in the regulation of foraging and flight behaviour in insects). According to the
      literature, flight metabolic rate is higher during pollen foraging than during
      nectar foraging, and nectar gives a higher energetic return relative to the
      foraging effort when compared with pollen. We thus propose that stress might be
      particularly detrimental to the performance of pollen foragers, and stressed bees
      prefer the energy-rich resource of nectar. In conclusion, stress, even at low
      levels, could have consequences for bee foraging behaviour and thereby the
      nutritional balance of the colony.

PMID- 29361593
TI  - SERT gene polymorphisms are associated with risk-taking behaviour and breeding
      parameters in wild great tits.
AB  - Individual differences in coping with potentially dangerous situations are
      affected by a combination of genetic and environmental factors. How genetic
      polymorphisms and behavioural variations are related to fitness is unknown. One
      of the candidate genes affecting a variety of behavioural processes, including
      impulsivity, anxiety and mood fluctuations in both humans and other vertebrates,
      is the serotonin transporter gene (SERT/SLC6A). The aim of this study was to
      assess an association between SERT genotypes and novelty-seeking and risk-taking
      behaviours as well as breeding parameters of great tits (Parus major) in a
      natural environment. We associated polymorphisms in the promoter exonic regions
      of the SERT gene with parental risk-taking-related behaviour and fitness traits.
      Our results show that: (1) risk-taking behaviour in our great tit population is
      linked to single nucleotide polymorphisms in the SERT gene exon 3 and exon 8; (2)
      the genotype-behaviour associations are consistent with the presence of different
      stressors; and (3) polymorphisms in exon 8 could be associated with fitness
      related traits, such as the start of egg-laying and hatching success. We showed
      for the first time that genetic variability of SERT plays an important role in
      shaping individual decision-making that affects fitness in a wild population.
      However, the results are based on one population and on the polymorphisms that
      are in a single gene. Therefore, replication studies are needed in order to
      confirm these preliminary results.

PMID- 29361594
TI  - Size-dependent avoidance of a strong magnetic anomaly in Caribbean spiny
      lobsters.
AB  - On a global scale, the geomagnetic field varies predictably across the Earth's
      surface, providing animals that migrate long distances with a reliable source of
      directional and positional information that can be used to guide their movements.
      In some locations, however, magnetic minerals in the Earth's crust generate an
      additional field that enhances or diminishes the overall field, resulting in
      unusually steep gradients of field intensity within a limited area. How animals
      respond to such magnetic anomalies is unclear. The Caribbean spiny lobster,
      Panulirus argus, is a benthic marine invertebrate that possesses a magnetic sense
      and is likely to encounter magnetic anomalies during migratory movements and
      homing. As a first step toward investigating whether such anomalies affect the
      behavior of lobsters, a two-choice preference experiment was conducted in which
      lobsters were allowed to select one of two artificial dens, one beneath a
      neodymium magnet and the other beneath a non-magnetic weight of similar size and
      mass (control). Significantly more lobsters selected the control den,
      demonstrating avoidance of the magnetic anomaly. In addition, lobster size was
      found to be a significant predictor of den choice: lobsters that selected the
      anomaly den were significantly smaller as a group than those that chose the
      control den. Taken together, these findings provide additional evidence for
      magnetoreception in spiny lobsters, raise the possibility of an ontogenetic shift
      in how lobsters respond to magnetic fields, and suggest that magnetic anomalies
      might influence lobster movement in the natural environment.

PMID- 29361595
TI  - Fasting enhances mitochondrial efficiency in duckling skeletal muscle by acting
      on the substrate oxidation system.
AB  - During food deprivation, animals must develop physiological responses to maximize
      energy conservation and survival. At the subcellular level, energy conservation
      is mainly achieved by a reduction in mitochondrial activity and an upregulation
      of oxidative phosphorylation efficiency. The aim of this study was to decipher
      mechanisms underlying the increased mitochondrial coupling efficiency reported in
      fasted birds. Mitochondrial oxidative phosphorylation activity, efficiency and
      membrane potential were measured in mitochondria isolated from the gastrocnemius
      muscle of ducklings. The content and activities of respiratory chain complexes
      were also determined. Results from ducklings fasted for 6 days were compared with
      ducklings fed ad libitum Here, we report that 6 days of fasting improved coupling
      efficiency in muscle mitochondria of ducklings by depressing proton-motive force
      through the downregulation of substrate oxidation reactions. Fasting did not
      change the basal proton conductance of mitochondria but largely decreased the
      oxidative phosphorylation activity, which was associated with decreased
      activities of succinate-cytochrome c reductase (complexes II-III) and citrate
      synthase, and altered contents in cytochromes b and c+c1 In contrast, fasting did
      not change cytochrome aa3 content or the activity of complexes I, II and IV.
      Altogether, these data show that the lower capacity of the respiratory machinery
      to pump protons in ducklings fasted for 6 days generates a lower membrane
      potential, which triggers a decreased proton leak activity and thus a higher
      coupling efficiency. We propose that the main site of action would be located at
      the level of co-enzyme Q pool/complex III of the electron transport chain.

PMID- 29361596
TI  - Malpighian tubules of Trichoplusia ni: recycling ions via gap junctions and
      switching between secretion and reabsorption of Na+ and K+ in the distal ileac
      plexus.
AB  - The functional kidney in insects consists of the Malpighian tubules and hindgut.
      Malpighian tubules secrete ions and fluid aiding in hydromineral homeostasis,
      acid-base balance and metabolic waste excretion. In many insects, including
      lepidopterans, the Malpighian tubule epithelium consists of principal cells (PCs)
      and secondary cells (SCs). The SCs in the Malpighian tubules of larvae of the
      lepidopteran Trichoplusia ni have been shown to reabsorb K+, transporting it in a
      direction opposite to that in the neighbouring PCs that secrete K+ One of the
      mechanisms that could enable such an arrangement is a gap junction (GJ)-based
      coupling of the two cell types. In the current study, we have immunolocalized GJ
      protein Innexin-2 to the PC-PC and SC-PC cell-cell borders. We have demonstrated
      that GJs in the SC-containing region of the Malpighian tubules enable Na+ and K+
      reabsorption by the SCs. We also demonstrated that in ion-loaded animals, PCs
      switch from Na+/K+ secretion to reabsorption, resulting in an ion-transporting
      phenotype similar to that of tubules with pharmacologically blocked GJs.
      Concomitantly, mRNA abundance encoding GJ proteins was downregulated. Finally, we
      observed that such PC-based reabsorption was only present in the distal ileac
      plexus connected to the rectal complex. We propose that this plasticity in the PC
      function in the distal ileac plexus is likely to be aimed at providing an ion
      supply for the SC function in this segment of the tubule.

PMID- 29361597
TI  - Variations on a theme: bumblebee learning flights from the nest and from flowers.
AB  - On leaving a significant place to which they will return, bees and wasps perform
      learning flights to acquire visual information to guide them back. The flights
      are set in different contexts, such as from their nest or a flower, which are
      functionally and visually different. The permanent and inconspicuous nest hole of
      a bumblebee worker is locatable primarily through nearby visual features, whereas
      a more transient flower advertises itself by its colour and shape. We compared
      the learning flights of bumblebees leaving their nest or a flower in an
      experimental situation in which the nest hole, flower and their surroundings were
      visually similar. Consequently, differences in learning flights could be
      attributed to the bee's internal state when leaving the nest or flower rather
      than to the visual scene. Flights at the flower were a quarter as long as those
      at the nest and more focused on the flower than its surroundings. Flights at the
      nest covered a larger area with the bees surveying a wider range of directions.
      For the initial third of the learning flight, bees kept within about 5 cm of the
      flower and nest hole, and tended to face and fixate the nest, flower and nearby
      visual features. The pattern of these fixations varied between nest and flower,
      and these differences were reflected in the bees' return flights to the nest and
      flower. Together, these findings suggest that learning flights are tuned to the
      bees' inherent expectations of the visual and functional properties of nests and
      flowers.

PMID- 29361598
TI  - Effects of mechanical disturbance and salinity stress on bioenergetics and
      burrowing behavior of the soft-shell clam Mya arenaria.
AB  - Bioturbation of sediments by burrowing organisms plays a key role in the
      functioning of coastal ecosystems. Burrowing is considered an energetically
      expensive activity, yet the energy costs of burrowing and the potential impacts
      of multiple stressors (such as salinity stress and wave action) on bioenergetics
      and burrowing performance of marine bioturbators are not well understood. We
      investigated the effects of mechanical disturbance and salinity stress on the
      burrowing behavior, aerobic capacity and energy expense of digging in a common
      marine bioturbator, the soft-shell clam Mya arenaria from the Baltic Sea (control
      salinity 15). Mya arenaria showed large individual variability in the burrowing
      efficiency, with an average of ~7% of the body energy reserves used per burial.
      Clams with higher mitochondrial capacity and lower energy expenditure per burial
      showed higher endurance. Acclimation for 3-4 weeks to low (5) or fluctuating (5
      15) salinity reduced the burrowing speed and the number of times the clams can
      rebury but did not affect the mitochondrial capacity of the whole body or the
      gill. Acclimation to the fluctuating salinity shifted the predominant fuel use
      for burrowing from proteins to lipids. Our data indicate that the reduced
      burrowing performance of clams under the salinity stress is not due to the
      limitations of energy availability or aerobic capacity but must involve other
      mechanisms (such as impaired muscle performance). The reduction in the burrowing
      capacity of clams due to salinity stress may have important implications for
      survival, activity and ecological functions of the clams in shallow coastal
      ecosystems.

PMID- 29361599
TI  - Disembodying the invisible: electrocommunication and social interactions by
      passive reception of a moving playback signal.
AB  - Mormyrid weakly electric fish have a special electrosensory modality that allows
      them to actively sense their environment and to communicate with conspecifics by
      emitting sequences of electric signals. Electroreception is mediated by different
      types of dermal electroreceptor organs for active electrolocation and
      electrocommunication, respectively. During electrocommunication, mormyrids
      exhibit stereotyped discharge sequences and locomotor patterns, which can be
      induced by playback of electric signals. This raises the question: what sensory
      information is required to initiate and sustain social interactions, and which
      electrosensory pathway mediates such interactions? By experimentally excluding
      stimuli from vision and the lateral line system, we show that Mormyrus rume
      proboscirostris can rely exclusively on its electrosensory system to track a
      mobile source of electric communication signals. Detection of electric playback
      signals induced discharge cessations, followed by double-pulse patterns. The
      animals tried to interact with the moving signal source and synchronized their
      discharge activity to the playback. These behaviors were absent in control trials
      without playback. Silencing the electric organ in some fish did not impair their
      ability to track the signal source. Silenced fish followed on trajectories
      similar to those obtained from intact animals, indicating that active
      electrolocation is no precondition for close-range interactions based on
      electrocommunication. However, some silenced animals changed their strategy when
      searching for the stationary playback source, which indicates passive sensing.
      Social interactions among mormyrids can therefore be induced and mediated by
      passive reception of electric communication signals without the need for
      perception of the location of the signal source through other senses.

PMID- 29361600
TI  - How does a slender tibia resist buckling? Effect of material, structural and
      geometric characteristics on buckling behaviour of the hindleg tibia in stick
      insect postembryonic development.
AB  - During the lifespan of the stick insect Carausius morosus, their long and narrow
      tibiae experience substantial compressive loads. The mechanical load on the
      tibiae increases as the weight of the insect rises. The increase in body weight
      is accompanied by a notable increase in the insect's body size and, accordingly,
      by an increase in the length of the tibiae. Both of these changes can raise the
      risk of buckling of the tibiae. In this study, we tracked changes in the material
      and geometric properties of the hindleg tibia of C. morosus during growth. The
      results show that although buckling (either by Euler buckling or local buckling)
      is the dominant failure mode under compression, the tibia is very capable of
      maintaining its buckling resistance in each postembryonic developmental stage.
      This is essentially the result of a compromise between the increasing slenderness
      of the tibia and its increasing material stiffness. The use of an optimal radius
      to thickness ratio, a soft resilin-dominated core, and chitin fibres oriented in
      both longitudinal and circumferential directions are presumably additional
      strategies preventing buckling of the tibia. This study, providing the first
      quantitative data on changes in the biomechanical properties of cuticle during
      the entire life of an insect, is expected to shed more light on the structure
      property-function relationship in this complex biological composite.

PMID- 29361601
TI  - Honey bee (Apis mellifera) sociability and nestmate affiliation are dependent on
      the social environment experienced post-eclosion.
AB  - Underpinning the formation of a social group is the motivation of individuals to
      aggregate and interact with conspecifics, termed sociability. Here, we developed
      an assay, inspired by vertebrate approaches to evaluate social behaviours, to
      simultaneously examine the development of honey bee (Apis mellifera) sociability
      and nestmate affiliation. Focal bees were placed in a testing chamber which was
      separated from groups of nestmates and conspecific non-nestmates by single-layer
      mesh screens. Assessing how much time bees spent contacting the two mesh screens
      allowed us to quantify simultaneously how much bees sought proximity and
      interaction with other bees and their preference for nestmates over non
      nestmates. Both sociability and nestmate affiliation could be detected soon after
      emergence as an adult. Isolation early in adult life impaired honey bee
      sociability but there was no evidence for a critical period for the development
      of the trait, as isolated bees exposed to their hive for 24 h when as old as 6
      days still recovered high levels of sociability. Our data show that, even for
      advanced social insects, sociability is a developmental phenomenon and experience
      dependent.

PMID- 29361602
TI  - Lizards assess complex social signals by lateralizing colour but not motion
      detection.
AB  - Vertebrates lateralize many behaviours including social interactions. Social
      displays typically comprise multiple components, yet our understanding of how
      these are processed comes from studies that typically examine responses to the
      dominant component or the complex signal as a whole. Here, we examined laterality
      in lizard responses to determine whether receivers separate the processing of
      motion and colour signal components in different brain hemispheres. In
      Psammophilus dorsalis, males display colours that dynamically change during
      courtship and aggressive interactions. We tested the visual grasp reflex of both
      sexes using robotic stimuli that mimicked two signal components: (1) multiple
      speeds of head-bobbing behaviour and (2) multiple colours. We found no laterality
      in response to different motion stimuli, indicating that motion similarly
      attracts attention from the two visual fields across sexes. Notably, receivers
      showed left visual field dominance to colours, especially when males were exposed
      to 'aggression-specific' colours and females to 'courtship-specific' colours.

PMID- 29361603
TI  - Low-cost synchronization of high-speed audio and video recordings in bio-acoustic
      experiments.
AB  - In this paper, we present a method for synchronizing high-speed audio and video
      recordings of bio-acoustic experiments. By embedding a random signal into the
      recorded video and audio data, robust synchronization of a diverse set of sensor
      streams can be performed without the need to keep detailed records. The
      synchronization can be performed using recording devices without dedicated
      synchronization inputs. We demonstrate the efficacy of the approach in two sets
      of experiments: behavioral experiments on different species of echolocating bats
      and the recordings of field crickets. We present the general operating principle
      of the synchronization method, discuss its synchronization strength and provide
      insights into how to construct such a device using off-the-shelf components.

PMID- 29361604
TI  - Cold tolerance is linked to osmoregulatory function of the hindgut in Locusta
      migratoria.
AB  - There is growing evidence that maintenance of ion and water balance determines
      cold tolerance in many insects. The hindgut of terrestrial insects is critical
      for maintaining organismal homeostasis as it regulates solute and water balance
      of the haemolymph. Here, we used ex vivo everted gut sacs of Locustamigratoria to
      examine the effects of temperature (0-30 degrees C), thermal acclimation,
      hypoxia, and ionic and osmotic forces on bulk water and ion (Na+, K+ and Cl-)
      movement across the rectal epithelium. These findings were related to
      simultaneous in vivo measurements of water and ion balance in locusts exposed to
      similar temperatures. As predicted, we observed a critical inhibition of net
      water and ion reabsorption at low temperature that was proportional to the in
      vivo loss of water and ion homeostasis. Further, cold-acclimated locusts, which
      are known to defend ion and water balance at low temperature, were characterised
      by improved reabsorptive capacity at low temperature. These findings strongly
      support the hypothesis that transport mechanisms in the hindgut at low
      temperature are essential for cold tolerance. The loss of osmoregulatory capacity
      at low temperature was primarily caused by reduced active transport, while rectal
      paracellular permeability to fluorescein isothiocyanate dextran was unchanged at
      0 and 30 degrees C. During cold exposure, water reabsorption was independent of
      major cation gradients across the epithelia, while a reduction in mucosal Cl-
      availability and an increase in mucosal osmolality markedly depressed water
      reabsorption. These findings are discussed in the context of existing knowledge
      and with suggestions for future physiological studies on cold acclimation and
      adaptation in insects.

PMID- 29361605
TI  - Renoguanylin stimulates apical CFTR translocation and decreases HCO3- secretion
      through PKA activity in the Gulf toadfish (Opsanus beta).
AB  - The guanylin peptides - guanylin, uroguanylin and renoguanylin (RGN) - are
      endogenously produced hormones in teleost fish enterocytes that are activators of
      guanylyl cyclase-C (GC-C) and are potent modulators of intestinal physiology,
      particularly in seawater teleosts. Most notably, they reverse normal net ion
      absorbing mechanisms that are vital to water absorption, an important process for
      seawater teleost survival. The role of guanylin-peptide stimulation of the
      intestine remains unclear, but it is hypothesized to facilitate the removal of
      solids from the intestine by providing fluid to enable their removal by
      peristalsis. The present study used one member of this group of peptides - RGN -
      to provide evidence for the prominent role that protein kinase A (PKA) plays in
      mediating the effects of guanylin-peptide stimulation in the posterior intestine
      of the Gulf toadfish (Opsanus beta). Protein kinase G was found to not mediate
      the intracellular effects of RGN, despite previous evidence showing that GC-C
      activation leads to higher cyclic guanosine monophosphate formation. RGN reversed
      the absorptive short-circuit current and increased conductance in the Gulf
      toadfish intestine. These effects are correlated to increased trafficking of the
      cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel to the
      apical membrane, which is negated by PKA inhibition. Moreover, RGN decreased HCO3
      secretion, likely by limiting apical HCO3-/Cl- exchange (possibly by reducing
      SLC26a6 activity), a reduction that was enhanced by PKA inhibition. RGN seems to
      alter PKA activity in the posterior intestine to recruit CFTR to the apical
      membrane and reduce HCO3- secretion.

PMID- 29361606
TI  - An improved method for detecting torpor entrance and arousal in a mammalian
      hibernator using heart rate data.
AB  - We used electrocardiogram (ECG) telemeters to measure the heart rate of
      hibernating Ictidomys tridecemlineatus (thirteen-lined ground squirrel). An
      increase in heart rate from 2.2 to 5 beats min-1 accurately identified arousal
      from torpor before any change in body temperature was detected. Variability in
      raw heart rate data was significantly reduced by a forward-backward Butterworth
      low-pass filter, allowing for discrete differential analysis. A decrease in
      filtered heart rate to 70% of maximum values in interbout euthermia (from
      approximately 312 to 235 beats min-1) accurately detected entrance into torpor
      bouts. At this point, body temperature had fallen from 36.1 degrees C to only
      34.7 degrees C, much higher than the 30 degrees C typically used to identify
      entrance. Using these heart rate criteria allowed advanced detection of entrance
      and arousal (detected 51.9 and 76 min earlier, respectively), compared with
      traditional body temperature criteria. This method will improve our ability to
      detect biochemical and molecular markers underlying these transition periods,
      during which many physiological changes occur.

PMID- 29361607
TI  - Magnificent magpie colours by feathers with layers of hollow melanosomes.
AB  - The blue secondary and purple-to-green tail feathers of magpies are structurally
      coloured owing to stacks of hollow, air-containing melanosomes embedded in the
      keratin matrix of the barbules. We investigated the spectral and spatial
      reflection characteristics of the feathers by applying (micro)spectrophotometry
      and imaging scatterometry. To interpret the spectral data, we performed optical
      modelling, applying the finite-difference time domain (FDTD) method as well as an
      effective media approach, treating the melanosome stacks as multi-layers with
      effective refractive indices dependent on the component media. The differently
      coloured magpie feathers are realised by adjusting the melanosome size, with the
      diameter of the melanosomes as well as their hollowness being the most sensitive
      parameters that influence the appearance of the feathers.

PMID- 29361608
TI  - Sleep deprivation negatively impacts reproductive output in Drosophila
      melanogaster.
AB  - Most animals sleep or exhibit a sleep-like state, yet the adaptive significance
      of this phenomenon remains unclear. Although reproductive deficits are associated
      with lifestyle-induced sleep deficiencies, how sleep loss affects reproductive
      physiology is poorly understood, even in model organisms. We aimed to bridge this
      mechanistic gap by impairing sleep in female fruit flies and testing its effect
      on egg output. We found that sleep deprivation by feeding caffeine or by
      mechanical perturbation resulted in decreased egg output. Transient activation of
      wake-promoting dopaminergic neurons decreased egg output in addition to sleep
      levels, thus demonstrating a direct negative impact of sleep deficit on
      reproductive output. Similarly, loss-of-function mutation in dopamine transporter
      fumin (fmn) led to both significant sleep loss and lowered fecundity. This
      demonstration of a direct relationship between sleep and reproductive fitness
      indicates a strong driving force for the evolution of sleep.

PMID- 29361609
TI  - Environmental enrichment modulates the response to chronic stress in zebrafish.
AB  - Several studies have shown that manipulations to the housing environment modulate
      susceptibility to stress in laboratory animals, mainly in rodents. Environmental
      enrichment (EE) is one such manipulation that promotes neuroprotection and
      neurogenesis, besides affecting behaviors such as drug self-administration.
      Zebrafish are a popular and useful animal model for behavioral neuroscience
      studies; however, studies evaluating the impact of housing conditions in this
      species are scarce. In this study, we verified the effects of EE on behavioral
      (novel tank test) and biochemical [cortisol and reactive oxygen species (ROS)]
      parameters in zebrafish submitted to unpredictable chronic stress (UCS).
      Consistent with our previous findings, UCS increased anxiety-like behavior,
      cortisol and ROS levels in zebrafish. EE for 21 or 28 days attenuated the effects
      induced by UCS on behavior and cortisol, and prevented the effects on ROS levels.
      Our findings reinforce the idea that EE exerts neuromodulatory effects across
      species, reducing vulnerability to stress and its biochemical impact. Also, these
      results indicate that zebrafish is a suitable model animal to study the
      behavioral effects and neurobiological mechanisms related to EE.

PMID- 29361611
TI  - How does the snakehead Channa argus survive in air? The combined roles of the
      suprabranchial chamber and physiological regulations during aerial respiration.
AB  - This study aimed to test the hypothesis that the aerial survival of the northern
      snakehead is involved not only with suprabranchial chamber respiration but also
      with physiological regulations. The aerial survival time and oxygen consumption
      rate (VO2) were determined in snakeheads with either normal or injured
      suprabranchial organs. Some hematological and biochemical parameters were
      assessed during aerial exposure. The results showed that resting VO2 decreased
      when switching from water to air in both the control and the suprabranchial organ
      injured fish, with decreases of 22.4% and 23.5%, respectively. Resting VO2 in air
      was not different between the control and the suprabranchial organ-injured fish.
      The red blood cell (RBC) count and hemoglobin concentration showed no marked
      changes, while RBC size increased when exposed to air. The liver lactate
      concentration remained unchanged, and the white muscle lactate concentration
      decreased when switching from water to air. The blood ammonia concentration
      tended to increase during aerial respiration. These results suggest that the
      aerial survival of the snakehead is positively associated with a combination of
      factors, including respiration of suprabranchial organs and other accessory
      organs, depressed metabolic demands and increased oxygen transport, and
      negatively associated with the accumulation of blood ammonia but not anaerobic
      metabolism.

PMID- 29361610
TI  - miR-9a mediates the role of Lethal giant larvae as an epithelial growth inhibitor
      in Drosophila.
AB  - Drosophila lethal giant larvae (lgl) encodes a conserved tumor suppressor with
      established roles in cell polarity, asymmetric division, and proliferation
      control. Lgl's human orthologs, HUGL1 and HUGL2, are altered in human cancers,
      however, its mechanistic role as a tumor suppressor remains poorly understood.
      Based on a previously established connection between Lgl and Fragile X protein
      (FMRP), a miRNA-associated translational regulator, we hypothesized that Lgl may
      exert its role as a tumor suppressor by interacting with the miRNA pathway.
      Consistent with this model, we found that lgl is a dominant modifier of
      Argonaute1 overexpression in the eye neuroepithelium. Using microarray profiling
      we identified a core set of ten miRNAs that are altered throughout tumorigenesis
      in Drosophila lgl mutants. Among these are several miRNAs previously linked to
      human cancers including miR-9a, which we found to be downregulated in lgl
      neuroepithelial tissues. To determine whether miR-9a can act as an effector of
      Lgl in vivo, we overexpressed it in the context of lgl knock-down by RNAi and
      found it able to reduce the overgrowth phenotype caused by Lgl loss in epithelia.
      Furthermore, cross-comparisons between miRNA and mRNA profiling in lgl mutant
      tissues and human breast cancer cells identified thrombospondin (tsp) as a common
      factor altered in both fly and human breast cancer tumorigenesis models. Our work
      provides the first evidence of a functional connection between Lgl and the miRNA
      pathway, demonstrates that miR-9a mediates Lgl's role in restricting epithelial
      proliferation, and provides novel insights into pathways controlled by Lgl during
      tumor progression.

PMID- 29361612
TI  - Spermine modulates fungal morphogenesis and activates plasma membrane H+-ATPase
      during yeast to hyphae transition.
AB  - Polyamines play a regulatory role in eukaryotic cell growth and morphogenesis.
      Despite many molecular advances, the underlying mechanism of action remains
      unclear. Here, we investigate a mechanism by which spermine affects the
      morphogenesis of a dimorphic fungal model of emerging relevance in plant
      interactions, Yarrowia lipolytica, through the recruitment of a phytohormone-like
      pathway involving activation of the plasma membrane P-type H+-ATPase.
      Morphological transition was followed microscopically, and the H+-ATPase activity
      was analyzed in isolated membrane vesicles. Proton flux and acidification were
      directly probed at living cell surfaces by a non-invasive selective ion electrode
      technique. Spermine and indol-3-acetic acid (IAA) induced the yeast-hypha
      transition, influencing the colony architecture. Spermine induced H+-ATPase
      activity and H+ efflux in living cells correlating with yeast-hypha dynamics.
      Pharmacological inhibition of spermine and IAA pathways prevented the physio
      morphological responses, and indicated that spermine could act upstream of the
      IAA pathway. This study provides the first compelling evidence on the fungal
      morphogenesis and colony development as modulated by a spermine-induced acid
      growth mechanism analogous to that previously postulated for the multicellular
      growth regulation of plants.

PMID- 29361613
TI  - Human hepatocyte depletion in the presence of HIV-1 infection in dual
      reconstituted humanized mice.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection impairs liver function, and
      liver diseases have become a leading cause of morbidity in infected patients. The
      immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric
      mice dually reconstituted with a human immune system and hepatocytes to address
      the relevance of the model to pathobiology questions related to human hepatocyte
      survival in the presence of systemic infection. TK-NOG males were transplanted
      with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human
      albumin concentration and the presence of human immune cells in blood were
      monitored for hepatocytes and immune reconstitution, and mice were infected with
      HIV-1. HIV-1-infected animals showed a decline in human albumin concentration
      with a significant reduction in percentage of human hepatocytes compared to
      uninfected mice. The decrease in human albumin levels correlated with a decline
      in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1
      infection elicited proinflammatory response in the immunological milieu of the
      liver in HIV-infected mice compared to uninfected animals, as determined by
      upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The
      inflammatory reaction associated with HIV-1 infection in vivo could contribute to
      the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse
      model is a feasible platform to investigate hepatocyte-related HIV-1
      immunopathogenesis.This article has an associated First Person interview with the
      first author of the paper.

PMID- 29361614
TI  - [Systemic Treatment of Malignant Pleural Mesothelioma].
AB  - Malignant pleural mesothelioma(MPM)is a highly aggressive tumor with a poor
      prognosis and an increasing incidence worldwide. The only standard first-line
      chemotherapy for patients with unresectable MPM is cisplatin(CDDP)plus peme-
      trexed(PEM)(CDDP/PEM), with a median overall survival of about 12months and a
      median progression-free survival(PFS) of less than 6 months. There are no
      treatments with proven benefit on survival for relapsed MPM patients. Therefore,
      novel therapeutic strategies are urgently required. Several molecular pathways
      involved in MPM have been identified; these include growth factor signaling
      pathways, cell cycle regulation, apoptosis, and angiogenesis. Fortunately,
      several agents targeting these processes have yielded promising results in
      preliminary trials. The addition of vascular endothelial growth factor(VEGF)
      inhibitor bevacizumab to the standard CDDP/PEM provides a 2.7-month survival
      benefit. Triple angiokinase inhibitor nintedanib, inhibiting the VEGFR, PDGFR,
      and FGFR, plus standard chemotherapy demonstrated a significant improvement in
      median PFS of 3.7 months in the overall study population, and a greater median
      PFS benefit of 4.0 months in epithelioid MPM. Mesothelin is an attractive target
      protein expressed on mesothelioma cells. Amatuximab, a chimeric anti-mesothelin
      antibody, in combination with CDDP/PEM, is currently being tested in randomized,
      double-blind, placebo-controlled phase II study. Anetumab ravtansine, mesothelin
      directed antibody drug conjugate, was evaluated in a randomized trial to compare
      to vinorelbine in patients with MPM who have high mesothelin expression and have
      progressed on CDDP/PEM-based first-line chemotherapy. However, anetumab
      ravtansine was not superior to vinorelbine in primary endpoint of PFS(4.3 months
      vs 4.5 months). Immune checkpoint blockades have demonstrated promising
      preclinical and clinical results in several cancer types, and are currently being
      investigated in clinical trials for MPM patients. PD-L1 expression in tumor
      tissue of MPM was reported, ranging between 20% and 70%. PD-L1 expression was
      significantly associated with a worse survival and overexpression was more common
      in sarcomatoid histology. This review summarizes clinical results for the latest
      systemic treatments in MPM.

PMID- 29361615
TI  - [Why Cardio-Oncology Is Necessary Today - From a Viewpoint of the Tumor Internal
      Medicine].
AB  - Cancer and cardiovascular disease are 2 major disease of the Japanese cause of
      death. Both patients with cancer complicated with cardiovascular disease and
      patients with cancer developing cardiovascular disorder during cancer therapyare
      increasing recently. Because aging is the onset risk factor, as for these, it is
      predicted that the patients with both cancer and cardiovascular disease increase
      more and more by the arrival of the aging society. Recently, the new research
      field called cardiooncology( or onco-cardiology)has been established, and the
      cooperation of medical oncologist and cardiologist becomes indispensable.

PMID- 29361616
TI  - [Onco-Cardiology - From the Standpoint of Cardiology].
AB  - In Japan, cardiovascular diseases are frequent complications in cancer patients
      owing to the rapidly aging population and changes in the overall lifestyle. In
      addition, new anticancer therapies have substantially improved the prognosis of
      cancer patients. Cardiotoxicity, also referred to as cancer treatment-related
      cardiac dysfunction, has become an important cause of morbidity and mortality in
      cancer patients. Cardiotoxicity may consist of hypertension, arrhythmia,
      thromboembolism, coronary artery disease, valvular disease, and left ventricular
      dysfunction which may progress to heart failure. Close interactions between
      cardiologists and oncologists are required for the optimal care of many cancer
      patients. Although cardiologists are expected to assist and advise the oncologist
      by providing diagnostic and prognostic information regarding developing
      cardiotoxicity, little is known about the cardiovascular pathogenic mechanisms
      associated with cancer treatment. Onco-cardiology is a medical subspecialty that
      focuses on the diagnosis and treatment of cardiotoxicity in cancer patients. This
      review describes the concept of onco-cardiology, and focuses on the management of
      cardiotoxicity that may arise during or after cancer therapy from the standpoint
      of cardiology. We also discuss noninvasive diagnostic options to identify and
      characterize cardiotoxicity.

PMID- 29361617
TI  - [Cardiotoxicity of Cancer Chemotherapy - Mechanisms and Therapeutic Approach].
AB  - Recent progress in cancer chemotherapy has improved the long-term outcome for
      cancer patients. Under such circumstances, it is increasingly of clinical
      importance to manage the cardiovascular complications, which are related to both
      cancer itself and adverse effects of cancer therapies. Among the most concerning
      as cardiovascular complications of cancer therapies is chemotherapy-induced
      cardiotoxicity or chemotherapy-related cardiac dysfunction(CTRCD). CTRCD has been
      intuitively classified according to the extent of structural abnormalities and
      degree of reversibility; type 1 is irreversible and dose-dependent with
      structural abnormalities, and type 2 is reversible after cessation of treatment
      and dose-independent without structural abnormalities. An example of drugs
      causing type 1 and 2 CTRCD is anthracyclines and trastuzumab, respectively,
      although both drugs are likely to induce cardiotoxicity through a combined
      action. In addition, there is growing awareness that CTRCD is also caused by anti
      VEGF inhibitors and tyrosine kinase inhibitors(TKIs), particularly in patients
      with cardiovascular comorbidities and risk factors. Interdisciplinary
      collaboration between oncology and cardiology specialists will contribute to the
      solution of unmet needs to elucidate epidemiologic and pathophysiologic aspects
      of CTRCD and to establish diagnostic strategies with risk prediction and evidence
      based therapeutic strategies against CTRCD in cancer patients and cancer
      survivors.

PMID- 29361618
TI  - [Management of Venous Thromboembolism in Cancer Patients].
AB  - The clinical relevance of the association between venous thromboembolism(VTE)and
      cancer is well documented. VTE is one of the leading causes of death in cancer
      patients. It would be an advantage to have knowledge on predictive parameters for
      the development of thrombosis and to be able to select cancer patients
      individually according to their riskprofiles. An elevated platelet count is
      associated with an increased riskof VTE in cancer patients. The biomarkers
      including D-dimer have been identified and used to extend the existing
      riskstratification. Treatment of VTE in cancer patients is complicated due to a
      high rate of recurrence in addition to a higher riskof bleeding during
      anticoagulation therapy. Current guidelines recommend low-molecular-weight
      heparin(LMWH)monotherapy over vitamin K antagonist(VKA)for the treatment of
      cancer-associated VTE. However, recent clinical study could not show any superior
      efficacy of LMWH over VKA in preventing VTE recurrence or overall mortality. The
      direct oral anticoagulants(DOACs)may be an effective treatment for VTE in cancer
      patients, although the riskreduction for recurrent VTE with the DOACs compared to
      LMWH has not been well assessed. Physicians should frequently re-evaluate the
      risk-benefit ratio of ongoing anticoagulation therapy in individual patient, in
      views of the overall clinical conditions including their quality of life and life
      expectancy.

PMID- 29361619
TI  - [Breast and Endocrine Tumor Supportive Care for Febrile Neutropenia in
      Chemotherapy - Current Situation and Future Perspective in Breast Cancer
      Treatment -].

PMID- 29361620
TI  - [I. Dose-Dense Chemotherapy as Perioperative Treatment in Breast Cancer].

PMID- 29361621
TI  - [II. Maintaining Relative Dose Intensity in Adjuvant Chemotherapy for Early
      Breast Cancer].

PMID- 29361622
TI  - [III. Indication of G-CSF in Advanced or Metastatic Breast Cancer].

PMID- 29361623
TI  - [Effect of Pegfilgrastim Primary Prophylactic Administration on Relative Dose
      Intensity(RDI)in Postoperative Adjuvant Chemotherapy(TC Therapy)for Breast Cancer
      - A Single-Center, Retrospective Study].
AB  - This study assessed the effect of pegfilgrastim in patients with early stage
      breast cancer who were receiving docetaxel and cyclophosphamide(TC)therapy(75mg/m
      / 2 docetaxel plus 600 mg/m2 cyclophosphamide). In total, 17 patients who were to
      receive 4 planned cycles of TC therapy every 3 weeks were included in this study.
      Of the 17 patients, 10 who received pegfilgrastim after January 2016 formed the
      Peg-G group and 7 who did not receive pegfilgrastim until December 2015 formed
      the control group. We observed a high successful execution rate and relative dose
      intensity(RDI)with docetaxel in both groups. The successful execution rates were
      100% in the Peg-G group and 42.8% in the control group. The RDI was 86.5%(65.4
      100%)in the Peg-G group and 52.5%(48.0-58.0%)in the control group. This study
      showed that the use of pegfilgrastim results in a high successful execution rate
      and RDI in patients with early stage breast cancer undergoing TC therapy.

PMID- 29361624
TI  - [Safety and Efficacy of Cisplatin Treatment after Carboplatin Hypersensitivity
      Reactions in Gynecologic Malignancies].
AB  - To investigate the safety and efficacy of cisplatin(CDDP)treatment after
      carboplatin(CBDCA)hypersensitivity reactions (CHSR)in gynecologic malignancies,
      we retrospectively reviewed the clinical records of 544 patients who underwent
      paclitaxel and CBDCA therapy(TC therapy). CHSR was observed in 18 patients. Eight
      patients were administered weekly paclitaxel and CDDP therapy(wTP
      therapy)continuously, to confirm that there was no CDDP hypersensitivity
      followingintravenous administration of 10 mgCDDP. At the onset of CHSR, the
      patients had received a median of 9 TC therapy cycles, and the median number of
      CBDCA administrations was 14. The frequency of CHSR was significantly higher in
      patients who received 7 cycles or more of TC therapy and CBDCA
      administration(p<0.0001). The median number of wTP therapy administrations was 8.
      Although CDDP hypersensitivity reactions were observed in 2 patients, their
      symptoms were mild(Grade 2, CTCAE v4.0). Of the 6 patients who received wTP
      therapy and had evaluable disease sites, 1, 2, 2 and 1 patients showed CR, PR,
      SD, and PD, respectively. The median progression-free survival in these 6
      patients was 9.5 months. For patients with the platinum- sensitive disease who
      have CHSR, CDDP could improve their prognosis.

PMID- 29361625
TI  - [A Case of Triple Negative Spindle Cell Carcinoma of the Breast and Improved
      Quality of Life Following Irinotecan Chemotherapy].
AB  - We report a case of triple negative spindle cell carcinoma of the breast,
      responsive to irinotecan chemotherapy. A 49-year old woman who had a tumor in the
      chest wall with a skin ulcer visited our hospital. After being diagnosed with
      triple negative spindle cell carcinoma of the breast, she underwent surgery,
      adjuvant chemotherapy, and radiation at the other hospital. Fourteen months after
      the surgery, she developed an ipsilateral breast tumor as a result of local
      recurrence. Since eribulin and paclitaxel plus bevacizumab chemotherapies were
      not effective, she was transferred to our hospital, and we administered
      irinotecan as third-line chemotherapy. Skin lesions and effusion were reduced and
      her quality of life improved for 4 months.

PMID- 29361626
TI  - [Secondary Dementia Due to Leptomeningeal Metastasis of Breast Cancer Improved by
      Whole Brain Radiation].
AB  - A 62-year-old woman received chemotherapy for breast cancer with bone metastasis
      and malignant pleural and pericardial effusion. She was examined by imaging for
      progressive cognitive impairment and headache. Enhanced MRI findings showed
      multiple solid tumors on brain surface, and brain perfusion scintigraphy showed
      blood flow decrease in both parietal lobes. She was diagnosed with secondary
      dementia due to leptomeningeal metastases of breast cancer, and whole brain
      external irradiation was performed(30 Gy/15 Fr). After treatment, multiple tumors
      were decreased in size and her cognitive impair- ment was improved.

PMID- 29361627
TI  - [A Case of Long-Term Survival after Resection of Metachronous Metastases to the
      Liver and Lungs from Primary Rectal Cancer].
AB  - A 81-year-old man had undergone high anterior resection for rectalcancer in 20XX.
      Abdominalcomputed tomography (CT)showed an isolated shadow of 2 cm in size in the
      liver, 9 years after surgery for colorectal cancer. We performed liver S4
      segmental resection and cholecystectomy. Histopathological examination confirmed
      liver metastases of rectal cancer. On examination of the liver metastasis 5 years
      after surgery, chest CT showed a shadow of 10mm in size in S6 of the left lung.
      We performed partialresection via video-assisted thoracic surgery(VATS)in
      20XX+14. Histopathological examination revealed lung metastases of rectal cancer.
      We believe that metachronous metastases from rectal cancer should be removed
      surgically if radicalcure is possible.

PMID- 29361628
TI  - [Clinical Analysis of Combination Chemotherapy Using High Dose Methotrexate,
      Rituximab, and Vincristine with or without Procarbazine for Elderly Patients with
      Diffuse Large B-Cell Lymphoma of the Central Nervous System].
AB  - We studied the clinical effects of high-dose methotrexate(HD-MTX)combined with
      rituximab and vincristine in 5 elderly patients, aged 65-83 years, with diffuse
      large B-cell lymphoma of the central nervous system(DLBCL CNS). Patients aged 65-
      71 years were given 3.0 g/m2 of HD-MTX, while patients aged 75-83 years were
      given 1.5 g/m2 of the drug. All patients showed responses; 1 CR and 1 PR in MTX
      3.0 g/m2 group, and 2 CRs and 1 PR in MTX 1.5 g/m2 group.

PMID- 29361629
TI  - [A Case of Cervical Lymph Node Metastasis from an Unknown Primary Cancer
      Controlled with Immunotherapy, Chemotherapy, and Surgery].
AB  - We present a case of cervical lymph node metastasis from an unknown primary
      cancer that was controlled with immunotherapy, chemotherapy, and surgery. The
      patient, a 61-year-old man, was referred to our department for treatment of a
      lesion in the left cervical lateral area. At the initial visit, the mass was
      covered by reddened skin and was elastic, hard, and immobile on palpation. The
      presence of a malignant disease such as malignant lymphoma or lymphadenitis
      because of infection by tubercle bacillus or Epstein-Barr virus was suspected on
      the basis of the clinical and magnetic resonance imaging findings. Biopsy and
      resection of the cervical mass was performed under general anesthesia. Because
      the pathological diagnosis during surgery indicated squamous cell carcinoma, the
      surgical approach was changed to neck dissection. Head, neck, and thoracic
      computed tomography and other examinations were performed to locate the primary
      cancer, but its origin remained unknown. Postoperative therapy consisted of
      chemotherapy and immunotherapy. The patient has been followed up for 4 years and
      10 months without any evidence of recurrence.

PMID- 29361630
TI  - Phase 1 trials of PEGylated recombinant human hyaluronidase PH20 in patients with
      advanced solid tumours.
AB  - This corrects the article DOI: 10.1038/bjc.2017.327.

PMID- 29361631
TI  - Evidence for genetic association between chromosome 1q loci and predisposition to
      colorectal neoplasia.

PMID- 29361632
TI  - Modeling visual-based pitch, lift and speed control strategies in hoverflies.
AB  - To avoid crashing onto the floor, a free falling fly needs to trigger its
      wingbeats quickly and control the orientation of its thrust accurately and
      swiftly to stabilize its pitch and hence its speed. Behavioural data have
      suggested that the vertical optic flow produced by the fall and crossing the
      visual field plays a key role in this anti-crash response. Free fall behavior
      analyses have also suggested that flying insect may not rely on graviception to
      stabilize their flight. Based on these two assumptions, we have developed a model
      which accounts for hoverflies' position and pitch orientation recorded in 3D with
      a fast stereo camera during experimental free falls. Our dynamic model shows that
      optic flow-based control combined with closed-loop control of the pitch suffice
      to stabilize the flight properly. In addition, our model sheds a new light on the
      visual-based feedback control of fly's pitch, lift and thrust. Since graviceptive
      cues are possibly not used by flying insects, the use of a vertical reference to
      control the pitch is discussed, based on the results obtained on a complete
      dynamic model of a virtual fly falling in a textured corridor. This model would
      provide a useful tool for understanding more clearly how insects may or not
      estimate their absolute attitude.

PMID- 29361636
TI  - [Psychological Care for a High Risk Group of Refugees - Concept of Care for the
      Yazidi Women and Children of the Sonderkontingent Baden-Wurttemberg in Freiburg].
AB  - After the genocide of Shingal in August 2014 in Northern Iraq, the humanitarian
      admissions program Sonderkontingent Baden-Wurttemberg "Schutzbedurftiger Frauen
      und Kinder aus dem Nordirak" was implemented. 1100 persons, most of them Yazidis,
      were hosted by different municipalities in Germany. The target group is a
      particularly vulnerable group of persons with a high risk for developing post
      traumatic stress disorder. We present the concept of care in Freiburg for 205
      Yazidi women and children in Freiburg. A stepped-care approach was developed for
      the psychological care to introduce the Yazidi people to the daily life and to
      the health care system in Germany. An outreach of psychological services and an
      interdisciplinary and multidisciplinary cooperation of all services involved were
      crucial.

PMID- 29361637
TI  - Secondary Hyperparathyroidism in HIV-Infected Patients in Central Europe.
AB  - Secondary hyperparathyroidism (sHPT) might be a contributor to increased risk of
      osteoporosis in adult HIV patients but there is little data available on this
      issue in this particular population. The aim of the study was to investigate the
      prevalence of sHPT in an HIV-infected population with normal kidney function and
      to evaluate its risk factors in HIV patients. This cross-sectional study was
      carried out in a single HIV center in Germany using routine data from patients
      with normal kidney function attending the clinic between January 1st and December
      31st, 2016. In total, 1263 patients were included [998 (79.0%) male, median age
      48 (IQR 38-54) years]. In 214 patients (16.9%) elevated PTH levels with low or
      normal calcium levels were found. Multivariate logistic regression modeling
      showed significant associations with elevated PTH for African ethnicity [OR: 2.12
      (95% CI: 1.42-3.16); p<0.001], low 25-hydroxyvitamin D levels [OR: 1.82 (95% CI:
      1.32-2.51); p<0.001], low calcium levels [OR 1.69 (95% CI: 1.22-2.33); p=0.001],
      and use of tenofovir disoproxil fumarate [OR 2.33 (95% CI: 1.62-3.36); p<0.001].
      Additional to common risk factors like vitamin D insufficiency and hypocalcemia,
      we found a significant association between the use of TDF and sHPT. Prospective
      data are needed to ascertain whether PTH-mediated bone loss is the underlying
      mechanism of TDF bone-toxicity. Additional screening of PTH even in HIV-infected
      patients with normal or low calcium levels may help to identify patients at
      increased risk of bone mineral density loss.

PMID- 29361638
TI  - ?

PMID- 29361639
TI  - Outcome of Low-Invasive Local Split-Thickness Lengthening for Iliotibial Band
      Friction Syndrome.
AB  - Conventional surgical methods for iliotibial band friction syndrome (ITBFS) may
      affect the iliotibial band (ITB), delaying return to sports activities or
      impeding performance. We have developed a minimally invasive method. This study
      retrospectively analyzed the outcomes of this procedure in individuals with
      ITBFS. This study included 34 knees of 31 individuals. Surgery involved
      lengthening the central part of the ITB by splitting it into a superficial and a
      deep layer, maintaining the anterior and posterior fibers immediately above the
      lateral epicondyle. Outcomes included time to resume sports activity, personal
      best times to run a 5000-m race before and after surgery, and 2-month post
      surgery muscle strengths. The mean postoperative time to return to competition
      was 5.8 weeks. Personal best times of 5000-m race improved in 13 of 17 runners.
      Two months post-surgery, the mean extensor muscle strengths on the healthy and
      affected sides did not significantly differ nor did the flexor muscle strengths.
      In ITBFS, the ITB itself is normal. Lengthening the limited region of the ITB
      immediately above the lateral femoral epicondyle removes the cause of ITBFS, with
      a reduction in inflammation. This technique resulted in early return to
      competition without degrading performance.

PMID- 29361640
TI  - Respiratory Rate Threshold Accurately Estimates the Second Lactate Threshold.
AB  - PURPOSE: The modified Dmax method can accurately determine the second lactate
      threshold (LT2), which is valuable for predicting aerobic performance and
      prescribing exercise. The purpose of this study is to determine if the modified
      Dmax method can accurately find thresholds in VE (VT2), VCO2 (VCO2T), RER (RERT),
      and RR (RRT) to estimate LT2. METHODS: Forty-one participants (females n=23,
      males n=18) completed an incremental exercise test to determine LT2, VT2, VCO2T,
      RERT, RRT, and blood lactate=4 mmol/L (La4). RESULTS: VT2 and RRT were strongly
      correlated with VO2 and HR at LT2, with very small bias and limits of agreement,
      indicating that VT2 and RRT provide accurate estimates of LT2 (VO2 at VT2-LT2
      mean difference=0.37+/-1.91 ml/kg/min, p=0.95; HR at VT2-LT2 mean
      difference=0.25+/-2.58 bpm, p=0.99; VO2 at RRT-LT2 mean difference 0.26+/-2.11
      ml/kg/min, p=0.99; HR at RRT-LT mean difference 0.44+/-3.31 bpm, p=0.99). VCO2T,
      RERT, and La4 were either accurate for VO2 or HR estimates of LT2, but not both.
      CONCLUSIONS: VT2 and RRT provide accurate estimates of LT2 using the modified
      Dmax method. There is the potential to use RRT in developing field tests to
      estimate LT2 in practical settings.

PMID- 29361641
TI  - [Surveillance of Supervised Flat-Sharing Communities Requiring Intensive Home
      Care: Results and Conclusions].
AB  - BACKGROUND: Patients with intensive care and long-term mechanical ventilation
      needs are increasingly cared for in supervised flat-sharing communities. The
      municipal public health and environment department of Munich audited nursing
      services between April 2015 and August 2016. METHODS: The structural analysis of
      the nursing services was conducted using standardised checklists, and statistical
      analysis was performed. In agreement with the residents and providers of the
      nursing service, flats were inspected. RESULTS: 20 of the 43 supervised flat
      sharing communities in Munich were designed for intensive care patients. Nine
      nursing services took care of them. Monitoring of organizational structures and
      hygiene management were found to be positive. There was room for improvement in
      practical implementation of hygiene standards. Requirements for personal
      qualifications and for emergencies such as electrical power outages have to be
      regulated. CONCLUSION: It was shown that regular consulting, instructions and
      auditing by the municipal public health and environment department have a
      positive effect on hygiene and emergency management. National and binding
      agreements still need to be worked out.

PMID- 29361642
TI  - [Clinical and sociodemographic Differences Between Patients with and without
      Migration Background in a Psychiatric Outpatient Service].
AB  - OBJECTIVE: A better understanding of specific sociodemographic and clinical
      factors in patients with migration background may help to significantly improve
      psychiatric treatment outcome of these patients. Therefore, we investigated these
      factors in a large sample of psychiatric outpatients. METHODS: N = 423
      psychiatric patients of a large outpatient service were assessed for
      sociodemographic variables as well as clinical variables including diagnosis,
      psychopharmacological treatment, treatment duration and current symptom load (SCL
      14). RESULTS: We found significant differences between patients with and without
      migration background in terms of sociodemographic and clinical factors such as
      education, employment and main diagnose. Patients with migration background had a
      significantly higher current symptom load, especially for somatic symptoms.
      CONCLUSION: The data underline the large differences between patients with and
      without migration background regarding sociodemographic and clinical factors.
      These differences should be considered in psychiatric treatment of these
      patients.

PMID- 29361643
TI  - [Dealing with Relatives of the Victims of the "Aktion T4" by the National
      Socialist Institutions as well as by Wuerttemberg Asylums].
AB  - The role of the relatives in the context of the "euthanasia" "Aktion T4" ("T4"
      campaign) has been controversially discussed in recent years. Based on documents
      of the National Socialist bureaucracy, statements of asylum psychiatrists in the
      year 1945 to the French occupation force as well as letters from relatives to
      Weissenau asylum in Wuerttemberg, these sources are analysed here in the light of
      the reactions of family members in respect to "Aktion T4". The results testify to
      a broad spectrum of responses of relatives, which are mainly characterised by
      fear, helplessness and protest.

PMID- 29361644
TI  - Correction: Relationship between Force-Velocity Profiles and 1,500-m Ergometer
      Performance in Young Rowers.

PMID- 29361645
TI  - Brugada Syndrome and Exercise Practice: Current Knowledge, Shortcomings and Open
      Questions.

PMID- 29361646
TI  - [Therapy-refractory cervical lymph node swelling and fever-A rare differential
      diagnosis in childhood].

PMID- 29361647
TI  - [HPV and oropharyngeal squamous cell cancer in the 8th edition of the TNM
      classification].
AB  - The 8th edition of the TNM classification, available since January 1st, 2017, has
      changed the classification of variou s tumors. For head and neck squamous cell
      cancer (HNSCC) of the oropharynx (OPC) the new edition distinguishes between HPV
      positive and HPV-negative disease to better reflect the prognostic implication of
      HPV associated disease. In many cases applying the new TNM-classification in HPV
      positive OPC results in downstaging of formerly locally advanced disease, i. e.
      UICC III/ IV, into localized disease UICC stage I/II. However, the data
      suggesting a better prognosis for patients with HPV associated disease is based
      on retrospective analyses of studies not primarily designed to answer the
      question whether or not de-escalated treatment regimes will maintain this
      survival advantage. This article dedicated to continued medical education (CME)
      attempts to shed light on many clinical questions still remaining concerning
      pathology, tumor and life style factors affecting prognosis in this patient
      population. Only a good understanding of these questions will enable us to
      interpret data correctly and apply the best possible therapy to our patients
      according to their risk profile to ensure the best possible outcome.

PMID- 29361648
TI  - Case of complete mesh migration into the stomach after mesh hiatoplasty for a
      hiatal hernia.
AB  - Mesh migration is a rare complication of surgery for a hiatal hernia. Here, we
      present the case of a 72-year-old who complained of dysphasia and bodyweight
      loss. Upper gastrointestinal endoscopy revealed incarcerated mesh in the lumen of
      the esophagogastric junction. Surgery was performed under both endoscopy and
      laparoscopy, and the mesh was successfully removed via gastrostomy. To the best
      of our knowledge, our case is the first in which mesh that had migrated into the
      esophagogastric junction was removed by a combination of laparoscopic and
      endoscopic procedure, although the cases of 17 patients in which mesh migrated
      into the stomach after mesh hiatoplasty have previously been reported in the
      literature.

PMID- 29361649
TI  - Peptide selection for the quantification of P-III-NP in human serum by mass
      spectrometry.
AB  - RATIONALE: Procollagen III amino-terminal propeptide (P-III-NP) is currently
      monitored in human doping control as a biomarker for growth hormone
      administration and also in clinical diagnostics using immunoassays. Drawbacks to
      this approach have been highlighted and research is ongoing to develop a mass
      spectrometric method to complement these methods. However, a lack of traceable
      reference material, the presence of post-translational modifications (PTMs), and
      small blood concentration complicate the development of targeted analytical
      methods for P-III-NP quantification. METHODS: Tryptic digest products of P-III-NP
      were assessed by liquid chromatography/mass spectrometry (LC/MS). In silico
      digestion was used to predict P-III-NP peptides for MS analysis; however, these
      excluded PTMs. With a priori knowledge of PTMs, we associated experimental P-III
      NP peptides with those derived by in silico digestion. Synthesized P-III-NP
      peptides, hT1 (human) and T5 (human/bovine), were used to develop sensitive micro
      and nano-flow LC/MS methods to analyse P-III-NP originating from human serum
      semi-quantitatively. RESULTS: P-III-NP peptides, T1 and T5, were identified using
      high-resolution accurate MS (HRAMS). PTMs modified the mass of observed peptides.
      N-terminal pyroglutamation (pE) in T1 and several hydroxylated prolines (hP) in
      T5 (G-X-hP motif) were observed. With PTM, hT1 and T5 were observed in a digest
      of immuno-captured P-III-NP by LC/MS. Using a semi-quantitative approach, hP-III
      NP at basal concentrations of 2 ng/mL (50 pmol) could be estimated from a 200-MUL
      sample volume. CONCLUSIONS: Consideration of PTMs is needed to identify P-III-NP
      peptides produced by digestion with trypsin. The information presented here now
      gives the most appropriate peptide sequences for synthesizing suitable reference
      materials required for quantification of human P-III-NP in blood and evidences
      methodology that is sufficiently sensitive to develop a quantitative method.

PMID- 29361650
TI  - Numerical Modeling of Methane Leakage from a Faulty Natural Gas Well into
      Fractured Tight Formations.
AB  - Horizontal drilling and hydraulic fracturing have enabled hydrocarbon recovery
      from unconventional reservoirs, but led to natural gas contamination of shallow
      groundwaters. We describe and apply numerical models of gas-phase migration
      associated with leaking natural gas wells. Three leakage scenarios are simulated:
      (1) high-pressure natural gas pulse released into a fractured aquifer; (2)
      continuous slow leakage into a tilted fractured formation; and (3) continuous
      slow leakage into an unfractured aquifer with fluvial channels, to facilitate a
      generalized evaluation of natural gas transport from faulty natural gas wells.
      High-pressure pulses of gas leakage into sparsely fractured media are needed to
      produce the extensive and rapid lateral spreading of free gas previously observed
      in field studies. Transport in fractures explains how methane can travel vastly
      different distances and directions laterally away from a leaking well, which
      leads to variable levels of methane contamination in nearby groundwater wells.
      Lower rates of methane leakage (<=1 Mcf/day) produce shorter length scales of gas
      transport than determined by the high-pressure scenario or field studies, unless
      aquifers have low vertical permeabilities (<=1 millidarcy) and fractures and
      bedding planes have sufficient tilt (~10 degrees ) to allow a lateral buoyancy
      component. Similarly, in fractured rock aquifers or where permeability is
      controlled by channelized fluvial deposits, lateral flow is not sufficiently
      developed to explain fast-developing gas contamination (0-3 months) or large
      length scales (~1 km) documented in field studies. Thus, current efforts to
      evaluate the frequency, mechanism, and impacts of natural gas leakage from faulty
      natural gas wells likely underestimate contributions from small-volume, low
      pressure leakage events.

PMID- 29361651
TI  - Effect of Heterogeneous Sediment Distributions on Hyporheic Flow in Physical and
      Numerical Models.
AB  - Variations in permeability have been found to significantly affect the flow of
      water though hyporheic systems, especially in regions with discontinuous
      transitions between distinct streambed lithologies. In this study, we
      probabilistically arranged two sediments (sand and sandy gravel) in a grid
      framework and imposed a single hyporheic flow cell across the grid to investigate
      how discontinuous permeability fields influence volumetric flow and residence
      time distributions. We used both a physical system and computer simulations to
      model flow through this sediment grid. A solution of blue dye and salt was pumped
      into the system and used to detect flow. We recorded the dye location using time
      lapse photography and measured the electrolytic conductivity levels as the water
      exited the system as a proxy for salt concentration. We also used a computer
      simulation to calculate dye-fronts, residence times, and exiting salt
      concentrations for the modeled system. Comparison between simulations and
      physical measurements yielded strong agreement. In further simulations with 300
      different grids, we found a strong correlation between volumetric flow rate and
      the placement of high permeability grid cells in regions of high hydraulic head
      gradients. One implication is that small anomalies in streambed permeability have
      a disproportionately large influence on hyporheic flows when located near steep
      head gradients such as steps. We also used moving averages with varying window
      sizes to investigate the effect of the abruptness of transitions between sediment
      types. We found that smoother permeability fields increased the volumetric flow
      rate and decreased the median residence times.

PMID- 29361652
TI  - Proposed diagnostic criteria for acute-on-chronic liver failure in Japan.
AB  - To establish diagnostic criteria for acute-on-chronic liver failure (ACLF) in
      Japan, the Intractable Hepato-Biliary Disease Study Group of Japan undertook a
      multicenter pilot survey for patients fulfilling the Asian Pacific Association
      for the Study of the Liver (APASL), Association for the Study of the Liver
      Chronic Liver Failure (EASL-Clif) Consortium, or Chinese Medical Association
      (CMA) diagnostic criteria for ACLF. The APASL criteria were suitable for
      screening Japanese patients with ACLF when patients whose conditions were
      triggered by gastrointestinal bleeding were included within the disease entity,
      and the EASL-Clif Consortium criteria were useful for classifying the severity of
      the patients' conditions. Based on these observations, the Study Group proposed
      the following diagnostic criteria for ACLF in Japan: patients with cirrhosis and
      a Child-Pugh score of 5-9 should be diagnosed as having ACLF when a deterioration
      of liver function (serum bilirubin level >=5.0 mg/dL and prothrombin time value
      <=40% of the standardized values and/or international normalization rate >=1.5)
      caused by severe liver damage develops within 28 days after acute insults, such
      as alcohol abuse, bacterial infection, gastrointestinal bleeding, or the
      exacerbation of underlying liver diseases. The severities of the patients can be
      classified into four grades depending on the extent of the deterioration in organ
      functions, including kidney, cerebral, blood coagulation, circulatory and
      respiratory functions, as well as liver function. The usefulness of these novel
      criteria should be validated prospectively in a large-scale cohort in the future.

PMID- 29361653
TI  - A Mamdani Adaptive Neural Fuzzy Inference System for Improvement of Groundwater
      Vulnerability.
AB  - Assessing groundwater vulnerability is an important procedure for sustainable
      water management. Various methods have been developed for effective assessment of
      groundwater vulnerability and protection. However, each method has its own
      conditions of use and, in practice; it is difficult to return the same results
      for the same site. The research conceptualized and developed an improved DRASTIC
      method using Mamdani Adaptive Neural Fuzzy Inference System (M-ANFIS-DRASTIC).
      DRASTIC and M-ANFIS-DRASTIC were applied in the Jorf aquifer, southeastern
      Tunisia, and results were compared. Results confirm that M-ANFIS-DRASTIC combined
      with geostatistical tools is more powerful, generated more precise vulnerability
      classes with very low estimation variance. Fuzzy logic has a power to produce
      more realistic aquifer vulnerability assessments and introduces new ways of
      modeling in hydrogeology using natural human language expressed by logic rules.

PMID- 29361654
TI  - Medicaid Reimbursement.

PMID- 29361655
TI  - Medicaid Restructuring.

PMID- 29361656
TI  - Medicaid Waivers.

PMID- 29361657
TI  - Pharmaceuticals and Medical Devices: Cost Savings.

PMID- 29361658
TI  - Pharmaceuticals and Medical Devices: Medicare Part D.

PMID- 29361659
TI  - Associations between Bethesda categories and tumor characteristics of
      conventional papillary thyroid carcinoma.
AB  - PURPOSE: The aim of this study was to investigate the associations of Bethesda
      categories III, V, and VI with the clinical and pathological features of thyroid
      nodules surgically confirmed as conventional papillary thyroid carcinomas (PTCs).
      METHODS: We analyzed 1,990 consecutive patients diagnosed with conventional PTC
      at surgery with preoperative Bethesda categories III, V, or VI. We determined the
      odds ratio (ORs) of the clinical and pathological variables associated with
      categories III and V, using category VI as the reference. RESULTS: Category III
      and V PTCs had a smaller pathological tumor size (OR, 0.934 and OR, 0.969,
      respectively) and less frequently had central lymph node metastasis (OR, 0.487
      and OR, 0.780, respectively) than category VI PTCs. Category III PTCs less
      frequently showed suspicious ultrasonographic features (OR, 0.296) than category
      VI PTCs, and category V PTCs less frequently had gross extrathyroidal extension,
      with borderline significance (OR, 0.643; P=0.059). CONCLUSION: Conventional PTCs
      with a preoperative Bethesda category of III or V may less frequently exhibit
      poor prognostic factors than those with malignant cytology.

PMID- 29361660
TI  - Pharmaceuticals and Medical Devices: Business Practices.

PMID- 29361661
TI  - Pharmaceuticals and Medical Devices: FDA Oversight.

PMID- 29361662
TI  - Pharmaceuticals and Medical Devices: FDA Oversight.

PMID- 29361663
TI  - 2018 Changes in the Journal.

PMID- 29361664
TI  - Noninvasive neurophysiological mapping of the lower urinary tract in adult and
      aging rhesus macaques.
AB  - The lower urinary tract (LUT) may be activated by spinal cord stimulation, but
      the physiological mapping characteristics of LUT activation with noninvasive
      transcutaneous spinal cord stimulation (TSCS) are not known. The effects of aging
      on the contractile properties of the detrusor are also not well understood.
      Therefore, TSCS was applied over the T10/T11 to L6/L7 spinous processes in adult
      ( n = 6) and aged ( n = 9) female rhesus macaques. A combination of urodynamic
      studies and electromyography recordings of the external urethral sphincter (EUS),
      external anal sphincter (EAS), and pelvic floor muscles was performed. Distinct
      functional maps were demonstrated for TSCS-evoked detrusor and urethral pressures
      and for the activation of the EUS, EAS, and pelvic floor muscles. The magnitude
      of responses for each peripheral target organ was dependent on TSCS location and
      strength. The strongest detrusor contraction was observed with TSCS at the L1/L2
      site in adults and the L3/L4 site in aged subjects. TSCS-evoked bladder pressure
      at the L1/L2 site was significantly higher for the adults compared with the aged
      subjects ( P < 0.05). Cumulative normalized TSCS-evoked pressures, calculated for
      five consecutive sites between the T11/T12 and L3/L4 levels, were significantly
      lower for aged compared with adult subjects ( P < 0.05). The aged animals also
      showed a caudal shift for the TSCS site that generated the strongest detrusor
      contraction. We conclude that natural aging in rhesus macaques is associated with
      decreased detrusor contractility, a finding of significant translational research
      relevance as detrusor underactivity is a common occurrence with aging in humans.
      NEW & NOTEWORTHY Transcutaneous spinal cord stimulation (TSCS) was used to map
      lower urinary tract function in adult and aged rhesus macaques. Aging was
      associated with decreased peak pressure responses to TSCS, reduced cumulative
      normalized evoked bladder pressure responses, and a caudal shift for the site
      generating the strongest TSCS-induced detrusor contraction. We demonstrate the
      utility of TSCS as a new diagnostic tool for detrusor contractility assessments
      and conclude that aging is associated with decreased detrusor contractility in
      primates.

PMID- 29361667
TI  - The continuing evolution of the Journal of Neurophysiology: 2018 update.
AB  - The Journal of Neurophysiology continues to evolve to meet the needs of its
      authors and readers. This article summarizes recent changes intended to improve
      our evaluation and communication of neuroscience research.

PMID- 29361666
TI  - beta-Adrenergic enhancement of neuronal excitability in the lateral amygdala is
      developmentally gated.
AB  - Noradrenergic signaling in the amygdala is important for processing threats and
      other emotionally salient stimuli, and beta-adrenergic receptor activation is
      known to enhance neuronal spiking in the lateral amygdala (LA) of juvenile
      animals. Nevertheless, intracellular recordings have not yet been conducted to
      determine the effect of beta-adrenergic receptor activation on spike properties
      in the adult LA, despite the potential significance of developmental changes
      between adolescence and adulthood. Here we demonstrate that the beta-adrenergic
      agonist isoproterenol (15 MUM) enhances spike frequency in dorsal LA principal
      neurons of juvenile male C57BL/6 mice and fails to do so in strain- and sex
      matched adults. Furthermore, we find that the age-dependent effect of
      isoproterenol on spike frequency is occluded by the GABAA receptor blocker
      picrotoxin (75 MUM), suggesting that beta-adrenergic receptors downregulate tonic
      inhibition specifically in juvenile animals. These findings indicate a
      significant shift during adolescence in the cellular mechanisms of beta
      adrenergic modulation in the amygdala. NEW & NOTEWORTHY beta-Adrenergic receptors
      (beta-ARs) in amygdala are important in processing emotionally salient stimuli.
      Most cellular recordings have examined juvenile animals, while behavioral data
      are often obtained from adults. We replicate findings showing that beta-ARs
      enhance spiking of principal cells in the lateral amygdala of juveniles, but we
      fail to find this in adults. These findings have notable scientific and clinical
      implications regarding the noradrenergic modulation of threat processing,
      alterations of which underlie fear and anxiety disorders.

PMID- 29361665
TI  - Nucleus accumbens core medium spiny neuron electrophysiological properties and
      partner preference behavior in the adult male prairie vole, Microtus ochrogaster.
AB  - Medium spiny neurons (MSNs) in the nucleus accumbens have long been implicated in
      the neurobiological mechanisms that underlie numerous social and motivated
      behaviors as studied in rodents such as rats. Recently, the prairie vole has
      emerged as an important model animal for studying social behaviors, particularly
      regarding monogamy because of its ability to form pair bonds. However, to our
      knowledge, no study has assessed intrinsic vole MSN electrophysiological
      properties or tested how these properties vary with the strength of the pair bond
      between partnered voles. Here we performed whole cell patch-clamp recordings of
      MSNs in acute brain slices of the nucleus accumbens core (NAc) of adult male
      voles exhibiting strong and weak preferences for their respective partnered
      females. We first document vole MSN electrophysiological properties and provide
      comparison to rat MSNs. Vole MSNs demonstrated many canonical
      electrophysiological attributes shared across species but exhibited notable
      differences in excitability compared with rat MSNs. Second, we assessed male vole
      partner preference behavior and tested whether MSN electrophysiological
      properties varied with partner preference strength. Male vole partner preference
      showed extensive variability. We found that decreases in miniature excitatory
      postsynaptic current amplitude and the slope of the evoked action potential
      firing rate to depolarizing current injection weakly associated with increased
      preference for the partnered female. This suggests that excitatory synaptic
      strength and neuronal excitability may be decreased in MSNs in males exhibiting
      stronger preference for a partnered female. Overall, these data provide extensive
      documentation of MSN electrophysiological characteristics and their relationship
      to social behavior in the prairie vole. NEW & NOTEWORTHY This research represents
      the first assessment of prairie vole nucleus accumbens core medium spiny neuron
      intrinsic electrophysiological properties and probes the relationship between
      cellular excitability and social behavior.

PMID- 29361668
TI  - Cutaneous exposure to lewisite causes acute kidney injury by invoking DNA damage
      and autophagic response.
AB  - Lewisite (2-chlorovinyldichloroarsine) is an organic arsenical chemical warfare
      agent that was developed and weaponized during World Wars I/II. Stockpiles of
      lewisite still exist in many parts of the world and pose potential environmental
      and human health threat. Exposure to lewisite and similar chemicals causes
      intense cutaneous inflammatory response. However, morbidity and mortality in the
      exposed population is not only the result of cutaneous damage but is also a
      result of systemic injury. Here, we provide data delineating the pathogenesis of
      acute kidney injury (AKI) following cutaneous exposure to lewisite and its analog
      phenylarsine oxide (PAO) in a murine model. Both agents caused renal tubular
      injury, characterized by loss of brush border in proximal tubules and tubular
      cell apoptosis accompanied by increases in serum creatinine, neutrophil
      gelatinase-associated lipocalin, and kidney injury molecule-1. Interestingly,
      lewisite exposure enhanced production of reactive oxygen species (ROS) in the
      kidney and resulted in the activation of autophagic and DNA damage response (DDR)
      signaling pathways with increased expression of beclin-1, autophagy-related gene
      7, and LC-3A/B-II and increased phosphorylation of gamma-H2A.X and checkpoint
      kinase 1/2, respectively. Terminal deoxyribonucleotide-transferase-mediated dUTP
      nick-end labeling-positive cells were detected in renal tubules along with
      enhanced proapoptotic BAX/cleaved caspase-3 and reduced antiapoptotic BCL2.
      Scavenging ROS by cutaneous postexposure application of the antioxidant N-acetyl
      l-cysteine reduced lewisite-induced autophagy and DNA damage. In summary, we
      provide evidence that topical exposure to lewisite causes AKI. The molecular
      mechanism underlying these changes involves ROS-dependent activation of autophagy
      and DDR pathway associated with the induction of apoptosis.

PMID- 29361669
TI  - SGLT2 inhibition in a kidney with reduced nephron number: modeling and analysis
      of solute transport and metabolism.
AB  - Sodium-glucose cotransporter 2 (SGLT2) inhibitors enhance urinary glucose, Na+
      and fluid excretion, and lower hyperglycemia in diabetes by targeting Na+ and
      glucose reabsorption along the proximal convoluted tubule. A goal of this study
      was to predict the effects of SGLT2 inhibitors in diabetic and nondiabetic
      patients with chronic kidney disease. To that end, we employed computational rat
      kidney models to explore how SGLT2 inhibition affects renal solute transport and
      metabolism when nephron populations are normal or reduced. Model simulations
      suggested that in a nondiabetic rat, acute and chronic SGLT2 inhibition induces
      glucosuria, diuresis, natriuresis, and kaliuresis. Those effects were stronger
      with chronic SGLT2 inhibition (due to SGLT1 downregulation) and tempered by
      nephron loss. In a diabetic rat with normal nephron number, acute SGLT2
      inhibition similarly elevated urine fluid, Na+, and K+ excretion, whereas the
      urinary excretory effects of chronic SGLT2 inhibition were attenuated in
      proportion to its plasma glucose level lowering effect. Nephron loss in a
      diabetic kidney was predicted to lower the glucosuric and blood glucose-reducing
      effect of chronic SGLT2 inhibition, but due to the high luminal glucose delivery
      in the remaining hyperfiltering nephrons, nephron loss enhanced proximal tubular
      paracellular Na+ secretion, thereby augmenting the natriuretic, diuretic, and
      kaliuretic effects. A proposed shift in oxygen-consuming active transport to the
      outer medulla, which may simulate systemic hypoxia and enhance erythropoiesis,
      was also preserved with nephron loss. These effects may contribute to the
      protective effects of SGLT2 inhibitors on blood pressure and heart failure
      observed in diabetic patients with chronic kidney diseases.

PMID- 29361670
TI  - Podocyte-specific knockin of PTEN protects kidney from hyperglycemia.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) has proven to be
      downregulated in podocytes challenged with high glucose (HG), and knockout of
      PTEN in podocytes aggravated the progression of diabetic kidney disease (DKD).
      However, whether podocyte-specific knockin of PTEN protects the kidney against
      hyperglycemia in vivo remains unknown. The inducible podocyte-specific PTEN
      knockin (PPKI) mice were generated by crossing newly created transgenic loxP-stop
      loxP-PTEN mice with podocin-iCreERT2 mice. Diabetes mellitus was induced in mice
      by intraperitoneal injection of streptozotocin at a dose of 150 mg/kg. In vitro,
      small interfering RNA and adenovirus interference were used to observe the role
      of PTEN in HG-treated podocytes. Our data demonstrated that PTEN was markedly
      reduced in the podocytes of patients with DKD and focal segmental
      glomerulosclerosis, as well as in those of db/db mice. Interestingly, podocyte
      specific knockin of PTEN significantly alleviated albuminuria, mesangial matrix
      expansion, effacement of podocyte foot processes, and incrassation of glomerular
      basement membrane in diabetic PPKI mice compared with wild-type diabetic mice,
      whereas no alteration was observed in the level of blood glucose. The potential
      renal protection of overexpressed PTEN in podocytes was partly attributed with an
      improvement in autophagy and motility and the inhibition of apoptosis. Our
      results showed that podocyte-specific knockin of PTEN protected the kidney
      against hyperglycemia in vivo , suggesting that targeting PTEN might be a novel
      and promising therapeutic strategy against DKD.

PMID- 29361671
TI  - Mechanisms and controversies in mutant Cul3-mediated familial hyperkalemic
      hypertension.
AB  - Autosomal dominant mutations in cullin-3 ( Cul3) cause the most severe form of
      familial hyperkalemic hypertension (FHHt). Cul3 mutations cause skipping of exon
      9, which results in an internal deletion of 57 amino acids from the CUL3 protein
      (CUL3-?9). The precise mechanism by which this altered form of CUL3 causes FHHt
      is controversial. CUL3 is a member of the cullin-RING ubiquitin ligase family
      that mediates ubiquitination and thus degradation of cellular proteins, including
      with-no-lysine [K] kinases (WNKs). In CUL3-?9-mediated FHHt, proteasomal
      degradation of WNKs is abrogated, leading to overactivation of the WNK targets
      sterile 20/SPS-1 related proline/alanine-rich kinase and oxidative stress
      response kinase-1, which directly phosphorylate and activate the thiazide
      sensitive Na+-Cl- cotransporter. Several groups have suggested different
      mechanisms by which CUL3-?9 causes FHHt. The majority of these are derived from
      in vitro data, but recently the Kurz group (Schumacher FR, Siew K, Zhang J,
      Johnson C, Wood N, Cleary SE, Al Maskari RS, Ferryman JT, Hardege I, Figg NL,
      Enchev R, Knebel A, O'Shaughnessy KM, Kurz T. EMBO Mol Med 7: 1285-1306, 2015)
      described the first mouse model of CUL3-?9-mediated FHHt. Analysis of this model
      suggested that CUL3-?9 is degraded in vivo, and thus Cul3 mutations cause FHHt by
      inducing haploinsufficiency. We recently directly tested this model but found
      that other dominant effects of CUL3-?9 must contribute to the development of
      FHHt. In this review, we focus on our current knowledge of CUL3-?9 action gained
      from in vitro and in vivo models that may help unravel this complex problem.

PMID- 29361672
TI  - Gastroprotective Effects of Sulphated Polysaccharides from the Alga Caulerpa
      mexicana Reducing Ethanol-Induced Gastric Damage.
AB  - The development of the gastric lesion is complex and the result of the imbalance
      between aggressive and protective factors, involving the generation of free
      radicals and disturbance in nitric oxide (NO) production. Sulphated
      polysaccharides (SP), from marine algae, are widely used in biotechnological and
      pharmaceutical areas. In this study, we evaluated the effects of SP from the
      green marine alga Caulerpa mexicana (Cm-SP) in ethanol-induced gastric damage
      models in mice. Cm-SP (2, 20, or 200 mg/kg), administered p.o., significantly
      reduced gastric damage, and these effects were inhibited through pretreatment
      with indomethacin. Cm-SP (200 mg/kg) prevented the ethanol-induced decline in
      glutathione and restored its normal level. Moreover, it was able to normalize the
      elevated thiobarbituric acid reactive substance levels. However, Cm-SP did not
      show any significant effects on NO2/NO3 level, when compared to the ethanol
      group. The pretreatment with L- NAME induced gastric mucosal damage and did not
      inhibit the gastroprotective effect of Cm-SP (200 mg/kg). In conclusion, the
      gastroprotective effects of Cm-SP in mice involve prostaglandins and reduction in
      the oxidative stress and are independent of NO.

PMID- 29361673
TI  - Investigating Potential Chromosomal Rearrangements during Laboratory Culture of
      Neisseria gonorrhoeae.
AB  - Comparisons of genome sequence data between different strains and isolates of
      Neisseria spp., such as Neisseria gonorrhoeae, reveal that over the evolutionary
      history of these organisms, large scale chromosomal rearrangements have occurred.
      Factors within the genomes, such as repetitive sequences and prophage, are
      believed to have contributed to these observations. However, the timescale in
      which rearrangements occur is not clear, nor whether it might be expected for
      them to happen in the laboratory. In this study, N. gonorrhoeae was repeatedly
      passaged in the laboratory and assessed for large scale chromosomal
      rearrangements. Using gonococcal strain NCCP11945, for which there is a complete
      genome sequence, cultures were passaged for eight weeks in the laboratory. The
      resulting genomic DNA was assessed using Pulsed Field Gel Electrophoresis,
      comparing the results to the predicted results from the genome sequence data.
      Three cultures generated Pulsed Field Gel Electrophoresis patterns that varied
      from the genomic data and were further investigated for potential chromosomal
      rearrangements.

PMID- 29361674
TI  - Effects of Polymethoxyflavonoids on Bone Loss Induced by Estrogen Deficiency and
      by LPS-Dependent Inflammation in Mice.
AB  - Polymethoxyflavonoids (PMFs) are a family of the natural compounds that mainly
      compise nobiletin, tangeretin, heptamethoxyflavone (HMF), and tetramethoxyflavone
      (TMF) in citrus fruits. PMFs have shown various biological functions, including
      anti-oxidative effects. We previously showed that nobiletin, tangeretin, and HMF
      all inhibited interleukin (IL)-1-mediated osteoclast differentiation via the
      inhibition of prostaglandin E2 synthesis. In this study, we created an original
      mixture of PMFs (nobiletin, tangeretin, HMF, and TMF) and examined whether or not
      PMFs exhibit co-operative inhibitory effects on osteoclastogenesis and bone
      resorption. In a coculture of bone marrow cells and osteoblasts, PMFs dose
      dependently inhibited IL-1-induced osteoclast differentiation and bone
      resorption. The optimum concentration of PMFs was lower than that of nobiletin
      alone in the suppression of osteoclast differentiation, suggesting that the
      potency of PMFs was stronger than that of nobiletin in vitro. The oral
      administration of PMFs recovered the femoral bone loss induced by estrogen
      deficiency in ovariectomized mice. We further tested the effects of PMFs on
      lipopolysaccharide-induced bone resorption in mouse alveolar bone. In an ex vivo
      experimental model for periodontitis, PMFs significantly suppressed the bone
      resorbing activity in organ cultures of mouse alveolar bone. These results
      indicate that a mixture of purified nobiletin, tangeretin, HMF, and TMF exhibits
      a co-operative inhibitory effect for the protection against bone loss in a mouse
      model of bone disease, suggesting that PMFs may be potential candidates for the
      prevention of bone resorption diseases, such as osteoporosis and periodontitis.

PMID- 29361675
TI  - Prevalence and Factors Associated with Fixed-Dose Combination Antiretroviral
      Drugs Adherence among HIV-Positive Pregnant Women on Option B Treatment in
      Mpumalanga Province, South Africa.
AB  - The possibility for all babies to be born and remain HIV-negative for the first
      year of life is achievable in South Africa. HIV-positive mothers' adherence to
      their antiretroviral medication is one of the crucial factors to achieve this
      target. Cross-sectional data were collected at 12 community health centres, over
      12 months (2014-2015), from 673 HIV-positive women, less than 6 months pregnant,
      attending antenatal care, and on Option B treatment. Adherence measures included
      the Adults AIDS Clinical Trials Group (AACTG) four-day measure, as well as the
      Visual Analog Scale (VAS) seven-day measure. Bivariate analyses and multivariate
      logistic regressions are presented. 78.8% of respondents were adherent on AACTG,
      while 68.8% reported VAS adherence. Bivariate analyses for increased adherence
      show significant associations with older age, less/no alcohol usage, disclosure
      of HIV status, higher HIV knowledge, no desire to avoid ARV side effects, low
      stigma, and low depression. AACTG showed a negative association with intimate
      partner violence. Multivariable logistic regression on AACTG and VAS adherence
      rates resulted in unique contributions to increased adherence of older age,
      less/no alcohol usage, higher HIV knowledge, lack of depression, and non
      disclosure. Programs targeting closer side effect monitoring, HIV disclosure, pre
      natal depression, alcohol intake, and HIV knowledge need consideration.

PMID- 29361676
TI  - Examining Public Perceptions about Lead in School Drinking Water: A Mixed-Methods
      Analysis of Twitter Response to an Environmental Health Hazard.
AB  - Exposure to lead has long been a community health concern in St. Louis, Missouri.
      The objective of this study was to examine public response to reports of elevated
      lead levels in school drinking water in St. Louis, Missouri via Twitter, a
      microblogging platform with over 320 million active users. We used a mixed
      methods design to examine Twitter user status updates, known as "tweets," from 18
      August to 31 December 2016. The number of tweets each day was recorded, and
      Twitter users were classified into five user types (General Public,
      Journalist/News, Health Professional/Academic, Politician/Government Official,
      and Non-Governmental Organization). A total of 492 tweets were identified during
      the study period. The majority of discourse on Twitter occurred during the two
      week period after initial media reports and was driven by members of the General
      Public. Thematic analysis of tweets revealed four themes: Information Sharing,
      Health Concerns, Sociodemographic Disparities, and Outrage. Twitter users
      characterized lead in school drinking water as an issue of environmental
      inequity. The findings of this study provide evidence that social media platforms
      can be utilized as valuable tools for public health researchers and practitioners
      to gauge public sentiment about environmental health issues, identify emerging
      community concerns, and inform future communication and research strategies
      regarding environmental health hazards.

PMID- 29361678
TI  - Synthesis and Antimicrobial Activity of Sulfur Derivatives of Quinolinium Salts.
AB  - A novel method for cleavage of the dithiine ring in 5,12-(dimethyl)
      thioqinantrenium bis-chloride 1 "via" reaction with sodium hydrosulfide leads to
      1-methyl-3-mercaptoquinoline-4(1H)-thione 2. Further transformation of thiol and
      thione functions of compound 2 leads to a series of sulfide and disulfide
      derivatives of quinolinium salts 4 and 6. 1-Methyl-4-chloro-3-benzylthioquinoline
      chloride 8 was obtained by N-alkylating 4-chloro-3-benzylthioquinoline using
      dimethyl sulfate. Antimicrobial activity of the obtained compounds was
      investigated using six Gram-positive and six Gram-negative bacterial strains, as
      well as Candida albicans yeast. Greater activity was demonstrated towards Gram
      positive strains. MIC values for compounds and with benzylthio 4d and benzoylthio
      4f substituents in 3-quinoline position were found to be in the 0.5-1 MUg/mL
      range, at a level similar to that of ciprofloxacin (reference). Compounds 4d and
      4f also demonstrated interesting antifungal properties (MIC = 1).

PMID- 29361679
TI  - Development of a Label-Free Immunosensor for Clusterin Detection as an
      Alzheimer's Biomarker.
AB  - Clusterin (CLU) has been associated with the clinical progression of Alzheimer's
      disease (AD) and described as a potential AD biomarker in blood plasma. Due to
      the enormous attention given to cerebrospinal fluid (CSF) biomarkers for the past
      couple of decades, recently found blood-based AD biomarkers like CLU have not yet
      been reported for biosensors. Herein, we report the electrochemical detection of
      CLU for the first time using a screen-printed carbon electrode (SPCE) modified
      with 1-pyrenebutyric acid N-hydroxysuccinimide ester (Pyr-NHS) and decorated with
      specific anti-CLU antibody fragments. This bifunctional linker molecule contains
      succinylimide ester to bind protein at one end while its pyrene moiety attaches
      to the carbon surface by means of pi-pi stacking. Cyclic voltammetric and square
      wave voltammetric studies showed the limit of detection down to 1 pg/mL and a
      linear concentration range of 1-100 pg/mL with good sensitivity. Detection of CLU
      in spiked human plasma was demonstrated with satisfactory recovery percentages to
      that of the calibration data. The proposed method facilitates the cost-effective
      and viable production of label-free point-of-care devices for the clinical
      diagnosis of AD.

PMID- 29361677
TI  - A Comparison of Oral and Intravenous Mouse Models of Listeriosis.
AB  - Listeria monocytogenes is one of several enteric microbes that is acquired
      orally, invades the gastric mucosa, and then disseminates to peripheral tissues
      to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with
      L. monocytogenes has been the most widely-used small animal model of listeriosis
      over the past few decades. The infection is highly reproducible and has been
      invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly
      CD8+ T cell responses to intracellular pathogens. However, the i.v. model
      completely bypasses the gut phase of the infection. Recent advances in generating
      both humanized mice and murinized bacteria, as well as the development of a
      foodborne route of transmission has reignited interest in studying oral models of
      listeriosis. In this review, we analyze previously published reports to highlight
      both the similarities and differences in tissue colonization and host response to
      infection using either oral or i.v. inoculation.

PMID- 29361680
TI  - Fate of Fecal Indicators in Resource-Oriented Sanitation Systems Using Nitrifying
      Bio-Treatment.
AB  - Hygienic fecal treatment in resource-oriented sanitation (ROS) systems is an
      important concern. Although the addition of nitrifying microorganisms is a
      sustainable fecal treatment method in ROS systems, it is essential to examine the
      cleanliness of this method. In this study, we investigated the fate of fecal
      indicators in source-separated fecal samples through tracking Escherichia coli
      and total coliforms. The effects of adding different amounts of Nitrosomonas
      europaea bio-seed, along with a constant amount of Nitrobacter winogradskyi bio
      seed, were studied. In intact feces samples, the pathogen population underwent an
      initial increase, followed by a slight decrease, and eventually became constant.
      Although the addition of nitrifying microorganisms initially enhanced the
      pathogen growth rate, it caused the reduction process to become more efficient in
      the long-term. In addition to a constant concentration of 10,000 cells of N.
      winogradskyi per 1 g feces, a minimum amount of 3000 and 7000 cells of N.
      europaea per 1 g feces could completely remove E. coli and total coliforms,
      respectively, in less than 25 days. Increasing the amount of bio-seeds added can
      further reduce the time required for total pathogen removal.

PMID- 29361681
TI  - icMRCI+Q Study of the Spectroscopic Properties of the 14 Lambda-S and 49 Omega
      States of the SiN- Anion in the Gas Phase.
AB  - This paper calculates the potential energy curves of the 14 Lambda-S and 49 Omega
      states, which come from the first three dissociation channels of the SiN- anion.
      These calculations are conducted using the valence internally contracted
      multireference configuration interaction and the Davidson correction approach.
      Core-valence correlation and scalar relativistic corrections are taken into
      account. The potential energies are extrapolated to the complete basis set limit.
      The spin-orbit coupling is computed using the state interaction approach with the
      Breit-Pauli Hamiltonian. We found that the X1Sigma+ (upsilon'' = 0-23) and
      a3Sigma+ (upsilon' = 0-2) states of SiN- are stable at the computed adiabatic
      electron affinity value of 23,262.27 cm-1 for SiN. Based on the calculated
      potential energy curves, the spectroscopic parameters and vibrational levels were
      determined for all stable and metastable Lambda-S and Omega states. The computed
      adiabatic electron affinity of SiN and the spectroscopic constants of SiN-
      (X1Sigma+) are all in agreement with the available experimental data. The
      d3Sigma+, 25Sigma+, 15Delta, and 15Sigma- quasi-bound states caused by avoided
      crossings were found. Calculations of the transition dipole moment of a3Sigma+1
      to X1Sigma+0+ are shown. Franck-Condon factors, Einstein coefficients, and
      radiative lifetimes of the transition from the a3Sigma+1 (upsilon' = 0-2) to the
      X1Sigma+0+ state are evaluated.

PMID- 29361682
TI  - Allelopathic and Bloom-Forming Picocyanobacteria in a Changing World.
AB  - Picocyanobacteria are extremely important organisms in the world's oceans and
      freshwater ecosystems. They play an essential role in primary production and
      their domination in phytoplankton biomass is common in both oligotrophic and
      eutrophic waters. Their role is expected to become even more relevant with the
      effect of climate change. However, this group of photoautotrophic organisms still
      remains insufficiently recognized. Only a few works have focused in detail on the
      occurrence of massive blooms of picocyanobacteria, their toxicity and
      allelopathic activity. Filling the gap in our knowledge about the mechanisms
      involved in the proliferation of these organisms could provide a better
      understanding of aquatic environments. In this review, we gathered and described
      recent information about allelopathic activity of picocyanobacteria and
      occurrence of their massive blooms in many aquatic ecosystems. We also examined
      the relationships between climate change and representative picocyanobacterial
      genera from freshwater, brackish and marine ecosystems. This work emphasizes the
      importance of studying the smallest picoplanktonic fractions of cyanobacteria.

PMID- 29361683
TI  - An Antibody-Immobilized Silica Inverse Opal Nanostructure for Label-Free Optical
      Biosensors.
AB  - Three-dimensional SiO2-based inverse opal (SiO2-IO) nanostructures were prepared
      for use as biosensors. SiO2-IO was fabricated by vertical deposition and
      calcination processes. Antibodies were immobilized on the surface of SiO2-IO
      using 3-aminopropyl trimethoxysilane (APTMS), a succinimidyl-[(N
      maleimidopropionamido)-tetraethyleneglycol] ester (NHS-PEG4-maleimide) cross
      linker, and protein G. The highly accessible surface and porous structure of SiO2
      IO were beneficial for capturing influenza viruses on the antibody-immobilized
      surfaces. Moreover, as the binding leads to the redshift of the reflectance peak,
      the influenza virus could be detected by simply monitoring the change in the
      reflectance spectrum without labeling. SiO2-IO showed high sensitivity in the
      range of 103-105 plaque forming unit (PFU) and high specificity to the influenza
      A (H1N1) virus. Due to its structural and optical properties, SiO2-IO is a
      promising material for the detection of the influenza virus. Our study provides a
      generalized sensing platform for biohazards as various sensing strategies can be
      employed through the surface functionalization of three-dimensional
      nanostructures.

PMID- 29361685
TI  - Glass Polarization Induced Drift of a Closed-Loop Micro-Accelerometer.
AB  - The glass polarization effects were introduced in this paper to study the main
      cause of turn-on drift phenomenon of closed-loop micro-accelerometers. The glass
      substrate underneath the sensitive silicon structure underwent a polarizing
      process when the DC bias voltage was applied. The slow polarizing process induced
      an additional electrostatic field to continually drag the movable mass block from
      one position to another so that the sensing capacitance was changed, which led to
      an output drift of micro-accelerometers. This drift was indirectly tested by
      experiments and could be sharply reduced by a shielding layer deposited on the
      glass substrate because the extra electrical filed was prohibited from generating
      extra electrostatic forces on the movable fingers of the mass block. The
      experimental results indicate the average magnitude of drift decreased about 73%,
      from 3.69 to 0.99 mV. The conclusions proposed in this paper showed a meaningful
      guideline to improve the stability of micro-devices based on silicon-on-glass
      structures.

PMID- 29361684
TI  - Micronutrient Gaps in Three Commercial Weight-Loss Diet Plans.
AB  - Weight-loss diets restrict intakes of energy and macronutrients but overlook
      micronutrient profiles. Commercial diet plans may provide insufficient
      micronutrients. We analyzed nutrient profiles of three plans and compared their
      micronutrient sufficiency to Dietary Reference Intakes (DRIs) for male U.S.
      adults. Hypocaloric vegan (Eat to Live-Vegan, Aggressive Weight Loss; ETL-VAWL),
      high-animal-protein low-carbohydrate (Fast Metabolism Diet; FMD) and weight
      maintenance (Eat, Drink and Be Healthy; EDH) diets were evaluated. Seven single
      day menus were sampled per diet (n = 21 menus, 7 menus/diet) and analyzed for 20
      micronutrients with the online nutrient tracker CRON-O-Meter. Without adjustment
      for energy intake, the ETL-VAWL diet failed to provide 90% of recommended amounts
      for B12, B3, D, E, calcium, selenium and zinc. The FMD diet was low (<90% DRI) in
      B1, D, E, calcium, magnesium and potassium. The EDH diet met >90% DRIs for all
      but vitamin D, calcium and potassium. Several micronutrients remained inadequate
      after adjustment to 2000 kcal/day: vitamin B12 in ETL-VAWL, calcium in FMD and
      EDH and vitamin D in all diets. Consistent with previous work, micronutrient
      deficits are prevalent in weight-loss diet plans. Special attention to
      micronutrient rich foods is required to reduce risk of micronutrient deficiency
      in design of commercial diets.

PMID- 29361686
TI  - Blood Vessel Formation and Bone Regeneration Potential of the Stromal Vascular
      Fraction Seeded on a Calcium Phosphate Scaffold in the Human Maxillary Sinus
      Floor Elevation Model.
AB  - Bone substitutes are used as alternatives for autologous bone grafts in patients
      undergoing maxillary sinus floor elevation (MSFE) for dental implant placement.
      However, bone substitutes lack osteoinductive and angiogenic potential. Addition
      of adipose stem cells (ASCs) may stimulate osteogenesis and osteoinduction, as
      well as angiogenesis. We aimed to evaluate the vascularization in relation to
      bone formation potential of the ASC-containing stromal vascular fraction (SVF) of
      adipose tissue, seeded on two types of calcium phosphate carriers, within the
      human MSFE model, in a phase I study. Autologous SVF was obtained from ten
      patients and seeded on beta-tricalcium phosphate (n = 5) or biphasic calcium
      phosphate carriers (n = 5), and used for MSFE in a one-step surgical procedure.
      After six months, biopsies were obtained during dental implant placement, and the
      quantification of the number of blood vessels was performed using
      histomorphometric analysis and immunohistochemical stainings for blood vessel
      markers, i.e., CD34 and alpha-smooth muscle actin. Bone percentages seemed to
      correlate with blood vessel formation and were higher in study versus control
      biopsies in the cranial area, in particular in beta-tricalcium phosphate-treated
      patients. This study shows the safety, feasibility, and efficiency of the use of
      ASCs in the human MSFE, and indicates a pro-angiogenic effect of SVF.

PMID- 29361687
TI  - Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of
      Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.
AB  - Targeting angiogenesis in the treatment of colorectal cancer (CRC) is a common
      strategy, for which potential predictive biomarkers have been studied. miRNAs are
      small non-coding RNAs involved in several processes including the angiogenic
      pathway. They are very stable in biological fluids, which turns them into
      potential circulating biomarkers. In this study, we considered a case series of
      patients with metastatic (m) CRC treated with a bevacizumab (B)-based treatment,
      enrolled in the prospective multicentric Italian Trial in Advanced Colorectal
      Cancer (ITACa). We then analyzed a panel of circulating miRNAs in relation to the
      patient outcome. In multivariate analysis, circulating basal levels of hsa-miR
      20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p resulted in being significantly
      associated with progression-free survival (PFS) (p = 0.027, p = 0.034 and p =
      0.039, respectively) and overall survival (OS) (p = 0.044, p = 0.024 and p =
      0.032, respectively). We also observed that an increase in hsa-miR-155-5p at the
      first clinical evaluation was significantly associated with shorter PFS (HR 3.03
      (95% CI 1.06-9.09), p = 0.040) and OS (HR 3.45 (95% CI 1.18-10.00), p = 0.024),
      with PFS and OS of 9.5 (95% CI 6.8-18.7) and 15.9 (95% CI 8.4-not reached),
      respectively, in patients with an increase >=30% of hsa-miR-155-5p and 22.3 (95%
      CI 10.2-25.5) and 42.9 (24.8-not reached) months, respectively, in patients
      without such increase. In conclusion, our results highlight the potential
      usefulness of circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa
      miR-155-5p in predicting the outcome of patients with mCRC treated with B. In
      addition, the variation of circulating hsa-miR-155-5p could also be indicative of
      the patient survival.

PMID- 29361688
TI  - Enhancing Flower Color through Simultaneous Expression of the B-peru and mPAP1
      Transcription Factors under Control of a Flower-Specific Promoter.
AB  - Flower color is a main target for flower breeding. A transgenic approach for
      flower color modification requires a transgene and a flower-specific promoter.
      Here, we expressed the B-peru gene encoding a basic helix loop helix (bHLH)
      transcription factor (TF) together with the mPAP1 gene encoding an R2R3 MYB TF to
      enhance flower color in tobacco (Nicotiana tabacum L.), using the tobacco
      anthocyanidin synthase (ANS) promoter (PANS) to drive flower-specific expression.
      The transgenic tobacco plants grew normally and produced either dark pink
      (PANSBP_DP) or dark red (PANSBP_DR) flowers. Quantitative real time polymerase
      chain reaction (qPCR) revealed that the expression of five structural genes in
      the flavonoid biosynthetic pathway increased significantly in both PANSBP_DP and
      PANSBP_DR lines, compared with the non-transformed (NT) control. Interestingly,
      the expression of two regulatory genes constituting the active MYB-bHLH-WD40
      repeat (WDR) (MBW) complex decreased significantly in the PANSBP_DR plants but
      not in the PANSBP_DP plants. Total flavonol and anthocyanin abundance correlated
      with flower color, with an increase of 1.6-43.2 fold in the PANSBP_DP plants and
      2.0-124.2 fold in the PANSBP_DR plants. Our results indicate that combinatorial
      expression of B-peru and mPAP1 genes under control of the ANS promoter can be a
      useful strategy for intensifying flower color without growth retardation.

PMID- 29361689
TI  - Colorectal Cancers: An Update on Their Molecular Pathology.
AB  - Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality
      worldwide. Rather than being a single, uniform disease type, accumulating
      evidence suggests that CRCs comprise a group of molecularly heterogeneous
      diseases that are characterized by a range of genomic and epigenomic alterations.
      This heterogeneity slows the development of molecular-targeted therapy as a form
      of precision medicine. Recent data regarding comprehensive molecular
      characterizations and molecular pathological examinations of CRCs have increased
      our understanding of the genomic and epigenomic landscapes of CRCs, which has
      enabled CRCs to be reclassified into biologically and clinically meaningful
      subtypes. The increased knowledge of the molecular pathological epidemiology of
      CRCs has permitted their evolution from a vaguely understood, heterogeneous group
      of diseases with variable clinical courses to characteristic molecular subtypes,
      a development that will allow the implementation of personalized therapies and
      better management of patients with CRC. This review provides a perspective
      regarding recent developments in our knowledge of the molecular and
      epidemiological landscapes of CRCs, including results of comprehensive molecular
      characterizations obtained from high-throughput analyses and the latest
      developments regarding their molecular pathologies, immunological biomarkers, and
      associated gut microbiome. Advances in our understanding of potential
      personalized therapies for molecularly specific subtypes are also reviewed.

PMID- 29361690
TI  - Contemporary Management of Localized Resectable Pancreatic Cancer.
AB  - Pancreatic cancer is the third most common cause of cancer deaths in the United
      States. Surgical resection with negative margins still constitutes the
      cornerstone of potentially curative therapy, but is possible only in 15-20% of
      patients at the time of initial diagnosis. Accumulating evidence suggests that
      the neoadjuvant approach may improve R0 resection rate in localized resectable
      and borderline resectable diseases, and potentially downstage locally advanced
      disease to achieve surgical resection, though the impact on survival is to be
      determined. Despite advancements in the last decade in developing effective
      combinational chemo-radio therapeutic options, preoperative treatment strategies,
      and better peri-operative care, pancreatic cancer continues to carry a dismal
      prognosis in the majority. Prodigious efforts are currently being made in
      optimizing the neoadjuvant therapy with a better toxicity profile, developing
      novel agents, imaging techniques, and identification of biomarkers for the
      disease. Advancement in our understanding of the tumor microenvironment and
      molecular pathology is urgently needed to facilitate the development of novel
      targeted and immunotherapies for this setting. In this review, we detail the
      current literature on contemporary management of resectable, borderline
      resectable and locally advanced pancreatic cancer with a focus on future
      directions in the field.

PMID- 29361692
TI  - Interplay between Selenium Levels and Replicative Senescence in WI-38 Human
      Fibroblasts: A Proteomic Approach.
AB  - Selenoproteins are essential components of antioxidant defense, redox
      homeostasis, and cell signaling in mammals, where selenium is found in the form
      of a rare amino acid, selenocysteine. Selenium, which is often limited both in
      food intake and cell culture media, is a strong regulator of selenoprotein
      expression and selenoenzyme activity. Aging is a slow, complex, and
      multifactorial process, resulting in a gradual and irreversible decline of
      various functions of the body. Several cellular aspects of organismal aging are
      recapitulated in the replicative senescence of cultured human diploid
      fibroblasts, such as embryonic lung fibroblast WI-38 cells. We previously
      reported that the long-term growth of young WI-38 cells with high (supplemented),
      moderate (control), or low (depleted) concentrations of selenium in the culture
      medium impacts their replicative lifespan, due to rapid changes in replicative
      senescence-associated markers and signaling pathways. In order to gain insight
      into the molecular link between selenium levels and replicative senescence, in
      the present work, we have applied a quantitative proteomic approach based on 2
      Dimensional Differential in-Gel Electrophoresis (2D-DIGE) to the study of young
      and presenescent cells grown in selenium-supplemented, control, or depleted
      media. Applying a restrictive cut-off (spot intensity +/-50% and a p value <
      0.05) to the 2D-DIGE analyses revealed 81 differentially expressed protein spots,
      from which 123 proteins of interest were identified by mass spectrometry. We
      compared the changes in protein abundance for three different conditions: (i)
      spots varying between young and presenescent cells, (ii) spots varying in
      response to selenium concentration in young cells, and (iii) spots varying in
      response to selenium concentration in presenescent cells. Interestingly, a 72%
      overlap between the impact of senescence and selenium was observed in our
      proteomic results, demonstrating a strong interplay between selenium,
      selenoproteins, and replicative senescence.

PMID- 29361693
TI  - Responses of Oat Grains to Fusarium poae and F. langsethiae Infections and
      Mycotoxin Contaminations.
AB  - Recent increases of Fusarium head blight (FHB) disease caused by infections with
      F. poae (FP) and F. langsethiae (FL) have been observed in oats. These pathogens
      are producers of nivalenol (NIV) and T-2/HT-2 toxin (T-2/HT-2), respectively,
      which are now considered major issues for cereal food and feed safety. To date,
      the impact of FP and FL on oat grains has not yet been identified, and little is
      known about oat resistance elements against these pathogens. In the present
      study, the impact of FL and FP on oat grains was assessed under different
      environmental conditions in field experiments with artificial inoculations. The
      severity of FP and FL infection on grains were compared across three field sites,
      and the resistance against NIV and T-2/HT2 accumulation was assessed for seven
      oat genotypes. Grain weight, beta-glucan content, and protein content were
      compared between infected and non-infected grains. Analyses of grain infection
      showed that FL was able to cause infection on the grain only in the field site
      with the highest relative humidity, whereas FP infected grains in all field
      sites. The FP infection of grains resulted in NIV contamination (between 30-500
      MUg/kg). The concentration of NIV in grains was not conditioned by environmental
      conditions. FL provoked an average contamination of grains with T-2/HT-2 (between
      15-132 MUg/kg). None of the genotypes was able to fully avoid toxin accumulation.
      The general resistance of oat grains against toxin accumulation was weak, and
      resistance against NIV accumulation was strongly impacted by the interaction
      between the genotype and the environment. Only the genotype with hull-less grains
      showed partial resistance to both NIV and T-2/HT-2 contamination. FP and FL
      infections could change the beta-glucan content in grains, depending on the
      genotypes and environmental conditions. FP and FL did not have a significant
      impact on the thousand kernel weight (TKW) and protein content. Hence, resistance
      against toxin accumulation remains the only indicator of FHB resistance in oat.
      Our results highlight the need for new oat genotypes with enhanced resistance
      against both NIV and T-2/HT-2 to ensure food and feed safety.

PMID- 29361691
TI  - Distinct Effects of Type I and III Interferons on Enteric Viruses.
AB  - Interferons (IFNs) are key host cytokines in the innate immune response to viral
      infection, and recent work has identified unique roles for IFN subtypes in
      regulating different aspects of infection. Currently emerging is a common theme
      that type III IFNs are critical in localized control of infection at mucosal
      barrier sites, while type I IFNs are important for broad systemic control of
      infections. The intestine is a particular site of interest for exploring these
      effects, as in addition to being the port of entry for a multitude of pathogens,
      it is a complex tissue with a variety of cell types as well as the presence of
      the intestinal microbiota. Here we focus on the roles of type I and III IFNs in
      control of enteric viruses, discussing what is known about signaling downstream
      from these cytokines, including induction of specific IFN-stimulated genes. We
      review viral strategies to evade IFN responses, effects of IFNs on the intestine,
      interactions between IFNs and the microbiota, and briefly discuss the role of
      IFNs in controlling viral infections at other barrier sites. Enhanced
      understanding of the coordinate roles of IFNs in control of viral infections may
      facilitate development of antiviral therapeutic strategies; here we highlight
      potential avenues for future exploration.

PMID- 29361694
TI  - Feasibility of e-Health Interventions on Smoking Cessation among Vietnamese
      Active Internet Users.
AB  - Introduction: Although e-health interventions are widely implemented as a
      supportive measure to smoking cessation, there is a lack of evidence in the
      feasibility of its application among Vietnamese youths, which is considered to be
      one of the most frequent internet using populations. This study assessed the
      quitting attempts among smokers and their preference and willingness to pay for
      smartphone-based cessation supporting applications in a sample of active internet
      users approached. Methods: A total of 1082 participants were recruited for the
      online-based survey from August to October 2015 in Vietnam. Information on
      sociodemographic characteristics, health information seeking behaviors on the
      internet, smoking status, quitting attempts and willingness to pay for smartphone
      based cessation supporting applications were collected. Multivariate logistic
      regression was used to determine the associated factors with current smoking and
      willingness to pay for the smoking cessation application. Results: About 11% of
      participants were current smokers while 73.4% had attempted to quit smoking. Only
      26.8% of the individuals indicated that they were willing to utilize a smartphone
      application to assist them in quitting. Participants who were male, had
      partners/spouse and lived at other places were more likely to smoke cigarette.
      Meanwhile, people who spent 50-70% of their online time to read health
      information were less likely to smoke. Results also show that living with family
      and never sharing health information on the internet were negatively associated
      with a participant's willingness to pay for the smartphone application.
      Meanwhile, people who highly trusted health information were more likely to be
      willing to pay for the application. Conclusions: This prevalence of smoking and
      associated factors can provide potential indicators for creating several public
      health interventions in the new environment with the increasing development of
      information technology. This study implies that in order to expand the coverage
      of smoking cessation interventions, we recommend the integration of e-health
      interventions with clinical- or telephone-based conventional models by providing
      smartphone applications and information on the internet from reliable sources.

PMID- 29361697
TI  - A Circular Microstrip Antenna Sensor for Direction Sensitive Strain Evaluation.
AB  - In this paper, a circular microstrip antenna for stress evaluation is studied.
      This kind of microstrip sensor can be utilized in structural health monitoring
      systems. Reflection coefficient S11 is measured to determine deformation/strain
      value. The proposed sensor is adhesively connected to the studied sample. Applied
      strain causes a change in patch geometry and influences current distribution both
      in patch and ground plane. Changing the current flow in patch influences the
      value of resonant frequency. In this paper, two different resonant frequencies
      were analysed because in each case, different current distributions in patch were
      obtained. The sensor was designed for operating frequency of 2.5 GHz (at
      fundamental mode), which results in a diameter less than 55 mm. Obtained
      sensitivity was up to 1 MHz/100 MPa, resolution depends on utilized vector
      network analyser. Moreover, the directional characteristics for both resonant
      frequencies were defined, studied using numerical model and verified by
      measurements. Thus far, microstrip antennas have been used in deformation
      measurement only if the direction of external force was well known. Obtained
      directional characteristics of the sensor allow the determination of direction
      and value of stress by one sensor. This method of measurement can be an
      alternative to the rosette strain gauge.

PMID- 29361695
TI  - Risk of Human Papillomavirus Infection in Cancer-Prone Individuals: What We Know.
AB  - Human papillomavirus (HPV) infections cause a significant proportion of cancers
      worldwide, predominantly squamous cell carcinomas (SCC) of the mucosas and skin.
      High-risk HPV types are associated with SCCs of the anogenital and oropharyngeal
      tract. HPV oncogene activities and the biology of SCCs have been intensely
      studied in laboratory models and humans. What remains largely unknown are host
      tissue and immune-related factors that determine an individual's susceptibility
      to infection and/or carcinogenesis. Such susceptibility factors could serve to
      identify those at greatest risk and spark individually tailored HPV and SCC
      prevention efforts. Fanconi anemia (FA) is an inherited DNA repair disorder that
      is in part characterized by extreme susceptibility to SCCs. An increased
      prevalence of HPV has been reported in affected individuals, and molecular and
      functional connections between FA, SCC, and HPV were established in laboratory
      models. However, the presence of HPV in some human FA tumors is controversial,
      and the extent of the etiological connections remains to be established. Herein,
      we discuss cellular, immunological, and phenotypic features of FA, placed into
      the context of HPV pathogenesis. The goal is to highlight this orphan disease as
      a unique model system to uncover host genetic and molecular HPV features, as well
      as SCC susceptibility factors.

PMID- 29361696
TI  - Nutrition Care after Discharge from Hospital: An Exploratory Analysis from the
      More-2-Eat Study.
AB  - Many patients leave hospital in poor nutritional states, yet little is known
      about the post-discharge nutrition care in which patients are engaged. This study
      describes the nutrition-care activities 30-days post-discharge reported by
      patients and what covariates are associated with these activities. Quasi-randomly
      selected patients recruited from 5 medical units across Canada (n = 513)
      consented to 30-days post-discharge data collection with 48.5% (n = 249)
      completing the telephone interview. Use of nutrition care post-discharge was
      reported and bivariate analysis completed with relevant covariates for the two
      most frequently reported activities, following recommendations post-discharge or
      use of oral nutritional supplements (ONS). A total of 42% (n = 110) received
      nutrition recommendations at hospital discharge, with 65% (n = 71/110) of these
      participants following those recommendations; 26.5% (n = 66) were taking ONS
      after hospitalization. Participants who followed recommendations were more likely
      to report following a special diet (p = 0.002), different from before their
      hospitalization (p = 0.008), compared to those who received recommendations, but
      reported not following them. Patients taking ONS were more likely to be at
      nutrition risk (p < 0.0001), malnourished (p = 0.0006), taking ONS in hospital (p
      = 0.01), had a lower HGS (p = 0.0013; males only), and less likely to believe
      they were eating enough to meet their body's needs (p = 0.005). This analysis
      provides new insights on nutrition-care post-discharge.

PMID- 29361698
TI  - A Diverse and Versatile Regiospecific Synthesis of Tetrasubstituted
      Alkylsulfanylimidazoles as p38alpha Mitogen-Activated Protein Kinase Inhibitors.
AB  - An alternative strategy for the synthesis of 1-aryl- and 1-alkyl-2-methylsulfanyl
      4-(4-fluorophenyl)-5-(pyridin-4-yl)imidazoles as potential p38alpha mitogen
      activated protein kinase inhibitors is reported. The regioselective N
      substitution of the imidazole ring was achieved by treatment of alpha
      aminoketones with different aryl or alkyl isothiocyanates. In contrast to
      previously published synthesis routes starting from 2-amino-4-methylpyridine, the
      presented route is characterized by a higher flexibility and a lower number of
      steps. This strategy was also applied to access 1-alkyl-2-methylsulfanyl-5-(4
      fluorophenyl)-4-(pyridin-4-yl)imidazoles in six steps starting from 2-chloro-4
      methylpyridine.

PMID- 29361699
TI  - L-Tree: A Local-Area-Learning-Based Tree Induction Algorithm for Image
      Classification.
AB  - The decision tree is one of the most effective tools for deriving meaningful
      outcomes from image data acquired from the visual sensors. Owing to its
      reliability, superior generalization abilities, and easy implementation, the tree
      model has been widely used in various applications. However, in image
      classification problems, conventional tree methods use only a few sparse
      attributes as the splitting criterion. Consequently, they suffer from several
      drawbacks in terms of performance and environmental sensitivity. To overcome
      these limitations, this paper introduces a new tree induction algorithm that
      classifies images on the basis of local area learning. To train our predictive
      model, we extract a random local area within the image and use it as a feature
      for classification. In addition, the self-organizing map, which is a clustering
      technique, is used for node learning. We also adopt a random sampled optimization
      technique to search for the optimal node. Finally, each trained node stores the
      weights that represent the training data and class probabilities. Thus, a
      recursively trained tree classifies the data hierarchically based on the local
      similarity at each node. The proposed tree is a type of predictive model that
      offers benefits in terms of image's semantic energy conservation compared with
      conventional tree methods. Consequently, it exhibits improved performance under
      various conditions, such as noise and illumination changes. Moreover, the
      proposed algorithm can improve the generalization ability owing to its
      randomness. In addition, it can be easily applied to ensemble techniques. To
      evaluate the performance of the proposed algorithm, we perform quantitative and
      qualitative comparisons with various tree-based methods using four image
      datasets. The results show that our algorithm not only involves a lower
      classification error than the conventional methods but also exhibits stable
      performance even under unfavorable conditions such as noise and illumination
      changes.

PMID- 29361700
TI  - A Semi-Pilot Photocatalytic Rotating Reactor (RFR) with Supported TiO2/Ag
      Catalysts for Water Treatment.
AB  - A four stage semi-pilot scale RFR reactor with ceramic disks as support for TiO2
      modified with silver particles was developed for the removal of organic
      pollutants. The design presented in this article is an adaptation of the rotating
      biological reactors (RBR) and its coupling with the modified catalyst provides
      additional advantages to designs where a catalyst in suspension is used. The
      optimal parameter of rotation was 54 rpm and the submerged surface of the disks
      offer a total contact area of 387 M2. The modified solid showed a decrease in the
      value of its bandgap compared to commercial titanium. The system has a semi
      automatic operation with a maximum reaction time of 50 h. Photo-activity tests
      show high conversion rates at low concentrations. The results conform to the
      Langmuir heterogeneous catalysis model.

PMID- 29361701
TI  - In Silico Study, Synthesis, and Cytotoxic Activities of Porphyrin Derivatives.
AB  - Five known porphyrins, 5,10,15,20-tetrakis(p-tolyl)porphyrin (TTP), 5,10,15,20
      tetrakis(p-bromophenyl)porphyrin (TBrPP), 5,10,15,20-tetrakis(p
      aminophenyl)porphyrin (TAPP), 5,10,15-tris(tolyl)-20-mono(p-nitrophenyl)porphyrin
      (TrTMNP), 5,10,15-tris(tolyl)-20-mono(p-aminophenyl)porphyrin (TrTMAP), and three
      novel porphyrin derivatives, 5,15-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]
      10,20-di(p-tolyl)porphyrin (DBECPDTP), 5,10-di-[bis(3,4
      ethylcarboxymethylenoxy)phenyl]-15,20-di-(methylpyrazole-4-yl)porphyrin
      (cDBECPDPzP), 5,15-di-[bis(3,4-ethylcarboxymethylenoxy)phenyl]-10,20-di
      (methylpyrazole-4-yl)porphyrin (DBECPDPzP), were used to study their interaction
      with protein targets (in silico study), and were synthesized. Their cytotoxic
      activities against cancer cell lines were tested using 3-(4,5-dimetiltiazol-2-il)
      2,5-difeniltetrazolium bromide (MTT) assay. The interaction of porphyrin
      derivatives with carbonic anhydrase IX (CAIX) and REV-ERBbeta proteins were
      studied by molecular docking and molecular dynamic simulation. In silico study
      results reveal that DBECPDPzP and TrTMNP showed the highest binding interaction
      with REV- ERBbeta and CAIX, respectively, and both complexes of DBECPDPzP-REV
      ERBbeta and TrTMNP-CAIX showed good and comparable stability during molecular
      dynamic simulation. The studied porphyrins have selective growth inhibition
      activities against tested cancer cells and are categorized as marginally active
      compounds based on their IC50.

PMID- 29361702
TI  - A 750 K Photocharge Linear Full Well in a 3.2 MUm HDR Pixel with Complementary
      Carrier Collection.
AB  - Mainly driven by automotive applications, there is an increasing interest in
      image sensors combining a high dynamic range (HDR) and immunity to the flicker
      issue. The native HDR pixel concept based on a parallel electron and hole
      collection for, respectively, a low signal level and a high signal level is
      particularly well-suited for this performance challenge. The theoretical
      performance of this pixel is modeled and compared to alternative HDR pixel
      architectures. This concept is proven with the fabrication of a 3.2 MUm pixel in
      a back-side illuminated (BSI) process including capacitive deep trench isolation
      (CDTI). The electron-based image uses a standard 4T architecture with a pinned
      diode and provides state-of-the-art low-light performance, which is not altered
      by the pixel modifications introduced for the hole collection. The hole-based
      image reaches 750 kh+ linear storage capability thanks to a 73 fF CDTI capacitor.
      Both images are taken from the same integration window, so the HDR reconstruction
      is not only immune to the flicker issue but also to motion artifacts.

PMID- 29361703
TI  - Detection of Antibodies to Seven Priority Pathogens in Backyard Poultry in
      Trinidad, West Indies.
AB  - Backyard poultry farms in Trinidad and Tobago (T&T) play a vital role in
      providing food and income for rural communities. There is currently no
      information on the presence and circulation of pathogens in backyard poultry
      farms in T&T, and little is known in relation to the potential risks of spread of
      these pathogens to the commercial poultry sector. In order to address this, serum
      samples were collected from 41 chickens on five backyard farms taken from
      selected locations in Trinidad. Samples were tested for antibodies to seven
      priority pathogens of poultry by enzyme-linked immunosorbent assay (ELISA).
      Antibodies were detected in 65% (CI 95%: 50-78%) of the sampled birds for
      Infectious bronchitis virus (IBV), 67.5% (CI 95%: 52-80%) for Infectious bursal
      disease virus (IBDV), 10% (CI 95%: 4-23%) for Newcastle disease virus (NDV), 0%
      (CI 95%: 0-0%) for Avian influenza virus (AIV), 0% (CI 95%: 0-0%) for West Nile
      virus (WNV), 31.7% (CI 95%: 20-47%) for Mycoplasm gallisepticum/synoviae and 0%
      (CI 95%: 0-0%) for Salmonella enterica serotype Enteritidis. These results reveal
      the presence and circulation of important pathogens of poultry in selected
      backyard farms in Trinidad. The results provide important information which
      should be taken into consideration when assessing the risks of pathogen
      transmission between commercial and backyard poultry farms, as well as between
      poultry and wild birds.

PMID- 29361704
TI  - Usefulness of a Telemedicine Program in Refractory Older Congestive Heart Failure
      Patients.
AB  - BACKGROUND: Home telemonitoring is a modern and effective disease management
      model that is able to improve medical care, quality of life, and prognosis of
      chronically ill patients, and to reduce expenditure. The objective of this study
      was to evaluate the efficacy, costs, and patients' and caregivers' acceptance of
      our model of telemedicine in a high-risk chronic heart failure (CHF) older
      population. METHODS: Patients with high risk/refractory CHF were included. In the
      case of alarm parameters' modifications, a cardiologist decided to inform the
      emergency department (ED), the patient's General Practioner, or to programme a
      clinical ambulatory control. RESULTS: Forty-eight CHF patients (28 males; 58.3%),
      with a mean age of 80.4 +/- 7.7 years, entered this clinical experience. During
      the 20-months follow-up, four patients dropped out from counselling (8.3%),
      ambulatory clinical control within-24 h was planned in 18% of patients, 11% of
      patients were admitted to an ED, and 18% were hospitalized. Thirteen patients
      (29.5%) died a cardiac death; hospital admissions for heart failure decreased
      during the year after the enrolment when compared to the year before (from 35 to
      12 acute HF hospitalizations/year; p = 0.0001). Moreover, in these HF patients
      followed, accesses to an ED for an acute episode of HF decompensation reduced
      from 21/year to five/year (p = 0.0001). The economic expenditure, calculated for
      the year before and after the enrolment, reduced from 116.856 Euros to 40.065
      Euros/year. CONCLUSIONS: A telemedicine surveillance in high-risk older CHF
      patients determines a continuous and active contact between patients/caregivers,
      the Heart Failure Clinic, and family physicians, permitting an early evaluation
      of signs and symptoms of acute decompensation.

PMID- 29361705
TI  - DBS in Treatment of Post-Traumatic Stress Disorder.
AB  - Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition for
      which pharmacological therapy is not always solvable. Various treatments have
      been suggested and deep brain stimulation (DBS) is currently under investigation
      for patients affected by PTSD. We review the neurocircuitry and up-to-date
      clinical concepts which are behind the use of DBS in posttraumatic stress
      disorder (PTSD). The role of DBS in treatment-refractory PTSD patients has been
      investigated relying on both preclinical and clinical studies. DBS for PTSD is in
      its preliminary phases and likely to provide hope for patients with medical
      refractory PTSD following the results of randomized controlled studies.

PMID- 29361706
TI  - A Multicentric T-Cell Lymphoma with a Plasmacytoid Morphology in a Dog.
AB  - An 8-year-old male (neutered) Labrador with a history of erythematous skin
      lesions and exercise intolerance for a prolonged period was suddenly found dead.
      Necropsy findings revealed an infiltrative, focally extensive mass which occupied
      25% of the cardiac interventricular septum. Severe endocardiosis was also found
      on the bicuspid and tricuspid valves. The submandibular lymph nodes and kidneys
      were bilaterally enlarged, and the pre-hepatic lymph node and spleen were also
      enlarged. Multiple dermal pustules were present around the mouth and on the ear,
      and small ulcers were present on the tongue. Histopathological examination
      detected the presence of neoplastic lymphocytes with a plasmacytoid morphology in
      these tissues as well as in the tongue and skin lesions. Immunohistochemical
      (CD3+/CD18+) evaluation was consistent with a T-cell lymphoma, which could be
      classified as a peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS).

PMID- 29361707
TI  - Implications of Combined Exposure to Household Air Pollution and HIV on
      Neurocognition in Children.
AB  - Air pollution exposure and HIV infection can each cause neurocognitive insult in
      children. The purpose of this study was to test whether children with combined
      high air pollution exposure and perinatal HIV infection have even greater risk of
      neurocognitive impairment. This was a cross-sectional study of HIV-uninfected
      unexposed (HUU) and HIV-infected children and their caregivers in Nairobi, Kenya.
      We used a detailed neuropsychological battery to evaluate neurocognitive
      functioning in several domains. We measured caregiver 24-h personal CO exposure
      as a proxy for child CO exposure and child urinary 1-hydroxypyrene (1-OHP), a
      biomarker for exposure to polycyclic aromatic hydrocarbons (PAHs). Median 24-h
      caregiver CO exposure was 6.1 and 3.7 ppm for 45 HIV-infected (mean age 6.6
      years) and 49 HUU (mean age 6.7 years), respectively; 48.5% of HIV-infected and
      38.6% of HUU had caregiver 24-h CO levels exceeding the WHO recommended level.
      Median 1-OHP exposure was 0.6 and 0.7 umol/mol creatinine among HIV-infected and
      HUU children, respectively. HIV-infected children with high urinary 1-OHP
      (exceeding 0.68 umol/mol creatinine) had significantly lower global cognition (p
      = 0.04), delayed memory (p = 0.01), and attention scores (p = 0.003). Among HUU
      children, urinary 1-OHP and caregiver 24-h caregiver CO were not significantly
      associated with neurocognitive function. Our findings suggest that combined
      chronic exposure to air pollutants and perinatal HIV infection may be associated
      with poorer neurocognitive outcomes. High prevalence of air pollution exposure
      highlights the need to reduce these exposures.

PMID- 29361710
TI  - Influence of Magnesium Ions in the Seawater Environment on the Improvement of the
      Corrosion Resistance of Low-Chromium-Alloy Steel.
AB  - This study examined the synergic effect of alloying the element Cr and the
      environmental element Mg2+ ions on the corrosion property of a low-alloy steel in
      seawater at 60  degrees C, by means of electrochemical impedance spectroscopy
      (EIS), linear polarization resistance (LPR) tests and weight-loss tests. The Mg2+
      ions in seawater played an important role in lowering the electron transfer of
      the rust layer in the Cr-containing steel. The corrosion resistance of the Cr
      containing steel is superior to that of blank steel in Mg2+ ions containing
      seawater. XPS and XRD results indicated that the formation of MgFe2O4 and a mixed
      layer (Cr oxide + FeCr2O4 + MgCr2O4) improved the corrosion resistance of the low
      alloy steel in the seawater.

PMID- 29361708
TI  - Abscisic Acid (ABA ) Promotes the Induction and Maintenance of Pear (Pyrus
      pyrifolia White Pear Group) Flower Bud Endodormancy.
AB  - Dormancy is an adaptive mechanism that allows temperate deciduous plants to
      survive unfavorable winter conditions. In the present work, we investigated the
      possible function of abscisic acid (ABA) on the endodormancy process in pear. The
      ABA content increased during pear flower bud endodormancy establishment and
      decreased towards endodormancy release. In total, 39 putative genes related to
      ABA metabolism and signal transductions were identified from pear genome. During
      the para- to endodormancy transition, PpNCED-2 and PpNCED-3 had high expression
      levels, while PpCYP707As expression levels were low. However, during
      endodormancy, the expression of PpCYP707A-3 sharply increased with increasing
      cold accumulation. At the same time, the ABA content of pear buds declined, and
      the percentage of bud breaks rapidly increased. On the other hand, the expression
      levels of PpPYLs, PpPP2Cs, PpSnRK2s, and PpABI4/ABI5s were also changed during
      the pear flower bud dormancy cycle. Furthermore, exogenous ABA application to
      para-dormant buds significantly reduced the bud breaks and accelerated the
      transition to endodormancy. During the whole treatment time, the expression level
      of PpPP2C-12 decreased to a greater extent in ABA-treated buds than in control.
      However, the expression levels of PpSnRK2-1, PpSnRK2-4, and PpABI5-1 were higher
      in ABA-treated buds. Our results indicated that PpCYP707A-3 and PpNCEDs play
      pivotal roles on the regulation of endodormancy release, while ABA signal
      transduction pathway also appears to be involved in the process. The present work
      provided the basic information about the function of ABA-related genes during
      pear flower bud dormancy process.

PMID- 29361711
TI  - 5-Bromo-4',5'-bis(dimethylamino)fluorescein: Synthesis and Photophysical Studies.
AB  - In this study, three new fluorescein derivatives-5-bromo-4',5'-dinitrofluorescein
      (BDNF), 5-bromo-4',5'-diaminofluorescein (BDAF), and 5-bromo-4',5'
      bis(dimethylamino)fluorescein (BBDMAF)-were synthesized and their pH-dependent
      protolytic equilibria were investigated. In particular, BBDMAF exhibited pH
      dependent fluorescence, showing strong emission only at pH 3-6. BBDMAF bears a
      bromine moiety and thus, can be used in various cross-coupling reactions to
      prepare derivatives and take advantage of its unique emission properties. To
      confirm this, the Suzuki and Sonogashira reactions of BBDMAF with phenylboronic
      acid and phenylacetylene, respectively, were performed, and the desired products
      were successfully obtained.

PMID- 29361712
TI  - Protective Mechanism of the Antioxidant Baicalein toward Hydroxyl Radical-Treated
      Bone Marrow-Derived Mesenchymal Stem Cells.
AB  - Our study explores the antioxidant and cytoprotective effects of baicalein and
      further discusses the possible mechanisms. A methyl thiazolyl tetrazolium (MTT)
      assay revealed that baicalein could considerably enhance the viability of
      hydroxyl radical-treated bone marrow-mesenchymal stem cells (bmMSCs) at 37-370
      uM. The highest viability rate was 120.4%. In subsequent studies, baicalein was
      observed to effectively scavenge hydroxyl radical and PTIO* radicals, reducing
      Fe3+ and Cu2+ ions. In the Fe2+-chelating UV-vis spectra, mixing of baicalein
      with Fe2+ yielded two evident redshifts (275 -> 279 nm and 324 -> 352 nm) and a
      broad absorption peak (lambdamax ~ 650 nm, epsilon = 1.6 * 103 L mol-1.cm-1).
      Finally, we compared the Fe2+-chelating UV-vis spectra of baicalein and its
      analogues, including 5-hydroxyflavone, 6-hydroxyflavone, 7-hydroxyflavone,
      catechol, pyrogallol, and chrysin. This analysis revealed that the 4-keto group
      of the C-ring played a role. The 5,6,7-trihydroxy-group (pyrogallol group) in the
      A-ring served as an auxochrome, enhancing the absorbance of the UV-vis spectra
      and deepening the color of the Fe2+-complex. We concluded that baicalein, as an
      effective hydroxyl radical-scavenger, can protect bmMSCs from hydroxyl radical
      mediated oxidative stress. Its hydroxyl radical-scavenging effects are likely
      exerted via two pathways: direct scavenging of hydroxyl radicals, possibly
      through electron transfer, and indirect inhibition of hydroxyl radical generation
      via Fe2+ chelation through the 4-keto-5,6,7-trihydroxy groups.

PMID- 29361709
TI  - Post-Transcriptional Regulation of Anti-Apoptotic BCL2 Family Members.
AB  - Anti-apoptotic B cell lymphoma 2 (BCL2) family members (BCL2, MCL1, BCLxL, BCLW,
      and BFL1) are key players in the regulation of intrinsic apoptosis. Dysregulation
      of these proteins not only impairs normal development, but also contributes to
      tumor progression and resistance to various anti-cancer therapies. Therefore,
      cells maintain strict control over the expression of anti-apoptotic BCL2 family
      members using multiple mechanisms. Over the past two decades, the importance of
      post-transcriptional regulation of mRNA in controlling gene expression and its
      impact on normal homeostasis and disease have begun to be appreciated. In this
      review, we discuss the RNA binding proteins (RBPs) and microRNAs (miRNAs) that
      mediate post-transcriptional regulation of the anti-apoptotic BCL2 family
      members. We describe their roles and impact on alternative splicing, mRNA
      turnover, and mRNA subcellular localization. We also point out the importance of
      future studies in characterizing the crosstalk between RBPs and miRNAs in
      regulating anti-apoptotic BCL2 family member expression and ultimately apoptosis.

PMID- 29361713
TI  - Preparation of 1D Hierarchical Material Mesosilica/Pal Composite and Its
      Performance in the Adsorption of Methyl Orange.
AB  - This paper highlights the synthesis of a one-dimensional (1D) hierarchical
      material mesosilica/palygorskite (Pal) composite and evaluates its adsorption
      performance for anionic dye methyl orange (MO) in comparison with Pal and Mobile
      crystalline material-41 (MCM-41). The Mesosilica/Pal composite is consisted of
      mesosilica coated Pal nanorods and prepared through a dual template approach
      using cetyltrimethyl ammonium bromide (CTAB) and Pal as soft and hard templates,
      respectively. The composition and structure of the resultant material was
      characterized by a scanning electron microscope (SEM), transmissionelectron
      microscopy (TEM), N2 adsorption-desorption analysis, small-angle X-Ray powder
      diffraction (XRD), and zeta potential measurement. Adsorption experiments were
      carried out with different absorbents at different contact times and pH levels.
      Compared with Pal and MCM-41, the mesosilica/Pal composite exhibited the best
      efficiency for MO adsorption. Its adsorption ratio is as high as 70.4%. Its
      adsorption equilibrium time is as short as 30 min. Results testify that the MO
      retention is promoted for the micro-mesoporous hierarchical structure and
      positive surface charge electrostatic interactions of the mesosilica/Pal
      composite. The regenerability of the mesosilica/Pal composite absorbent was also
      assessed. 1D morphology makes it facile to separate from aqueous solutions. It
      can be effortlessly recovered and reused for up to nine cycles.

PMID- 29361714
TI  - Overhead Transmission Line Sag Estimation Using a Simple Optomechanical System
      with Chirped Fiber Bragg Gratings. Part 1: Preliminary Measurements.
AB  - A method of measuring the power line wire sag using optical sensors that are
      insensitive to high electromagnetic fields was proposed. The advantage of this
      technique is that it is a non-invasive measurement of power line wire elongation
      using a unique optomechanical system. The proposed method replaces the sag of the
      power line wire with an extension of the control sample and then an expansion of
      the attached chirped fiber Bragg grating. This paper presents the results of the
      first measurements made on real aluminum-conducting steel-reinforced wire,
      frequently used for power line construction. It has been shown that the proper
      selection of the CFBG (chirped fiber Bragg grating) transducer and the
      appropriate choice of optical parameters of such a sensor will allow for high
      sensitivity of the line wire elongation and sag while reducing the sensitivity to
      the temperature. It has been shown that with a simple optomechanical system, a
      non-invasive measurement of the power line wire sag that is insensitive to
      temperature changes and the influence of high electromagnetic fields can be
      achieved.

PMID- 29361715
TI  - Bioactivity-Guided Screening of Wound-Healing Active Constituents from American
      Cockroach (Periplaneta americana).
AB  - Ethanol extract (EE) from Periplaneta americana (PA) is the main ingredient of
      Kangfuxin, which is a popular traditional chinese medicine (TCM) and has long
      been used for the clinical treatment of burns, wounds and ulcers. We compared the
      wound-healing activities of three extracts of PA using cutaneous wound-healing in
      mice as the bioactivity model. These three extracts were EE, total polysaccharide
      and total protein. We also tracked bioactive fractions in the EE by organic
      reagent extraction, column chromatography and HPLC. Seven compounds were
      successfully identified from the water elution fraction of the EE of PA using
      UPLC-MS. Among these compounds, four compounds (P2, P3, P4, P5(1)) were first
      reported in PA. Some of these compounds have been previously reported to have
      various pharmacological activities that could contribute to the high wound
      healing activity of PA.

PMID- 29361717
TI  - Pharmacy Practice and Education in Latvia.
AB  - The PHARMINE ("Pharmacy Education in Europe") project studied the organisation of
      pharmacy practice and education in the member states of the European Union (EU).
      The work was carried out using an electronic survey sent to chosen pharmacy
      representatives. The surveys of the individual member states are now being
      published as reference documents. This paper presents the results of the PHARMINE
      survey on pharmacy practice and education in Latvia. In the light of this, we
      examine the harmonisation of practice and education in Latvia with EU norms.

PMID- 29361716
TI  - Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium
      elegans Extract Administration to Rats.
AB  - Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific
      region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects.
      However, detailed studies of the toxicology of GEE have not been performed. We
      evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley
      (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000
      mg/kg/day, although compound-colored stools and diarrhea were observed in both
      sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000
      mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over
      14 days and 13 weeks. GEE did not induce any significant toxicological changes in
      either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no
      adverse effects, in terms of clinical signs, mortality, body mass, food
      consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry,
      necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000
      mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to
      be >2000 mg/kg/day, and no pathology was identified in potential target organs.
      Therefore, this study indicates that repeated oral dosing with GEE is safe in CD
      rats.

PMID- 29361718
TI  - An IMU-Aided Body-Shadowing Error Compensation Method for Indoor Bluetooth
      Positioning.
AB  - Research on indoor positioning technologies has recently become a hotspot because
      of the huge social and economic potential of indoor location-based services
      (ILBS). Wireless positioning signals have a considerable attenuation in received
      signal strength (RSS) when transmitting through human bodies, which would cause
      significant ranging and positioning errors in RSS-based systems. This paper
      mainly focuses on the body-shadowing impairment of RSS-based ranging and
      positioning, and derives a mathematical expression of the relation between the
      body-shadowing effect and the positioning error. In addition, an inertial
      measurement unit-aided (IMU-aided) body-shadowing detection strategy is designed,
      and an error compensation model is established to mitigate the effect of body
      shadowing. A Bluetooth positioning algorithm with body-shadowing error
      compensation (BP-BEC) is then proposed to improve both the positioning accuracy
      and the robustness in indoor body-shadowing environments. Experiments are
      conducted in two indoor test beds, and the performance of both the BP-BEC
      algorithm and the algorithms without body-shadowing error compensation (named no
      BEC) is evaluated. The results show that the BP-BEC outperforms the no-BEC by
      about 60.1% and 73.6% in terms of positioning accuracy and robustness,
      respectively. Moreover, the execution time of the BP-BEC algorithm is also
      evaluated, and results show that the convergence speed of the proposed algorithm
      has an insignificant effect on real-time localization.

PMID- 29361719
TI  - Antioxidant and Cytoprotective Effects of the Di-O-Caffeoylquinic Acid Family:
      The Mechanism, Structure-Activity Relationship, and Conformational Effect.
AB  - In this study, a series of di-O-caffeoylquinic acids (di-COQs) were
      systematically investigated for their antioxidant and cytoprotective effects
      towards *OH-damaged bone marrow-derived mesenchymal stem cells (bmMSCs). Five di
      COQs were measured using a set of antioxidant assays. The results show that
      adjacent 4,5-Di-O-caffeoylquinic acid (4,5-COQ) and 3,4-di-O-caffeoylquinic acid
      (3,4-COQ) always gave lower IC50 values than did non-adjacent di-COQs. In the
      Fe2+-chelating assay, 4,5-COQ and 3,4-COQ presented greater UV-Vis spectra and
      darker colors than did non-adjacent di-COQs. In the UPLC-ESI-MS/MS analysis, no
      corresponding radical adduct formation (RAF) peak was found in the reaction
      products of di-COQs with PTIO*. In the MTT assay, all di-COQs (especially 1,5
      COQ, 1,3-COQ, and 4,5-COQ) dose-dependently increased the cellular viabilities of
      *OH-damaged bmMSCs. Based on this evidence, we conclude that the five antioxidant
      di-COQs can protect bmMSCs from *OH-induced damage. Their antioxidant mechanisms
      may include electron-transfer (ET), H+-transfer, and Fe2+-chelating, except for
      RAF. Two adjacent di-COQs (4,5-COQ and 3,4-COQ) always possessed a higher
      antioxidant ability than the non-adjacent di-COQs (1,3-COQ, 1,5-COQ, and 3,5-COQ)
      in chemical models. However, non-adjacent 1,3-COQ and 1,5-COQ exhibited a higher
      cytoprotective effect than did adjacent di-COQs. These differences can be
      attributed to the relative positions of two caffeoyl moieties and, ultimately, to
      the conformational effect from the cyclohexane skeleton.

PMID- 29361720
TI  - Distribution Assessments of Coumarins from Angelicae Pubescentis Radix in Rat
      Cerebrospinal Fluid and Brain by Liquid Chromatography Tandem Mass Spectrometry
      Analysis.
AB  - Angelicae Pubescentis Radix (APR) is a widely-used traditional Chinese medicine.
      Pharmacological studies have begun to probe its biological activities on
      neurological disorders recently. To assess the brain penetration and distribution
      of APR, a validated ultra-performance liquid chromatography tandem mass
      spectrometry method was applied to the simultaneous determinations of the main
      coumarins from APR in the rat cerebrospinal fluid (CSF) and brain after oral
      administration of APR extract, including psoralen, xanthotoxin, bergapten,
      isoimperatorin, columbianetin, columbianetin acetate, columbianadin,
      oxypeucedanin hydrate, angelol B, osthole, meranzin hydrate and nodakenetin. Most
      of the tested coumarins entered the rat CSF and brain quickly, and double-peak
      phenomena in concentration-time curves were similar to those of their plasma
      pharmacokinetics. Columbianetin had the highest concentration in the CSF and
      brain, while psoralen and columbianetin acetate had the largest percent of
      CSF/plasma and brain/plasma, indicating that these three coumarins may be worthy
      of further research on the possible nervous effects. Correlations between the in
      vivo brain distributions and plasma pharmacokinetics of these coumarins were well
      verified. These results provided valuable information for the overall in vivo
      brain distribution characteristics of APR and also for its further studies on the
      active substances for the central nervous system.

PMID- 29361721
TI  - Poly(hydroxyalkanoate)s-Based Hydrophobic Coatings for the Protection of Stone in
      Cultural Heritage.
AB  - Reversibility is a mandatory requirement for materials used in heritage
      conservation, including hydrophobic protectives. Nevertheless, current
      protectives for stone are not actually reversible as they remain on the surfaces
      for a long time after their hydrophobicity is lost and can hardly be removed.
      Ineffective and aged coatings may jeopardise the stone re-treatability and
      further conservation interventions. This paper aims at investigating the
      performance of PHAs-based coatings for stone protection, their main potential
      being the 'reversibility by biodegradation' once water repellency ended. The
      biopolymer coatings were applied to three different kinds of stone,
      representative of lithotypes used in historic architecture: sandstone, limestone
      and marble. Spray, poultice and dip-coating were tested as coating techniques.
      The effectiveness and compatibility of the protectives were evaluated in terms of
      capillary water absorption, static and dynamic contact angles, water vapour
      diffusion, colour alteration and surface morphology. The stones' wettability
      after application of two commercial protectives was investigated too, for
      comparison. Finally, samples were subjected to artificial ageing to investigate
      their solar light stability. Promising results in terms of efficacy and
      compatibility were obtained, although the PHAs-based formulations developed here
      still need improvement for increased durability and on-site applicability.

PMID- 29361722
TI  - Textile Concentric Ring Electrodes for ECG Recording Based on Screen-Printing
      Technology.
AB  - Among many of the electrode designs used in electrocardiography (ECG), concentric
      ring electrodes (CREs) are one of the most promising due to their enhanced
      spatial resolution. Their development has undergone a great push due to their use
      in recent years; however, they are not yet widely used in clinical practice. CRE
      implementation in textiles will lead to a low cost, flexible, comfortable, and
      robust electrode capable of detecting high spatial resolution ECG signals. A
      textile CRE set has been designed and developed using screen-printing technology.
      This is a mature technology in the textile industry and, therefore, does not
      require heavy investments. Inks employed as conductive elements have been silver
      and a conducting polymer (poly (3,4-ethylenedioxythiophene) polystyrene
      sulfonate; PEDOT:PSS). Conducting polymers have biocompatibility advantages, they
      can be used with flexible substrates, and they are available for several printing
      technologies. CREs implemented with both inks have been compared by analyzing
      their electric features and their performance in detecting ECG signals. The
      results reveal that silver CREs present a higher average thickness and slightly
      lower skin-electrode impedance than PEDOT:PSS CREs. As for ECG recordings with
      subjects at rest, both CREs allowed the uptake of bipolar concentric ECG signals
      (BC-ECG) with signal-to-noise ratios similar to that of conventional ECG
      recordings. Regarding the saturation and alterations of ECGs captured with
      textile CREs caused by intentional subject movements, silver CREs presented a
      more stable response (fewer saturations and alterations) than those of PEDOT:PSS.
      Moreover, BC-ECG signals provided higher spatial resolution compared to
      conventional ECG. This improved spatial resolution was manifested in the
      identification of P1 and P2 waves of atrial activity in most of the BC-ECG
      signals. It can be concluded that textile silver CREs are more suitable than
      those of PEDOT:PSS for obtaining BC-ECG records. These developed textile
      electrodes bring the use of CREs closer to the clinical environment.

PMID- 29361723
TI  - Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus
      on Old and New Drugs.
AB  - Prevention and treatment of dyslipidemia should be considered as an integral part
      of individual cardiovascular prevention interventions, which should be addressed
      primarily to those at higher risk who benefit most. To date, statins remain the
      first-choice therapy, as they have been shown to reduce the risk of major
      vascular events by lowering low-density lipoprotein cholesterol (LDL-C). However,
      due to adherence to statin therapy or statin resistance, many patients do not
      reach LDL-C target levels. Ezetimibe, fibrates, and nicotinic acid represent the
      second-choice drugs to be used in combination with statins if lipid targets
      cannot be reached. In addition, anti-PCSK9 drugs (evolocumab and alirocumab)
      provide an effective solution for patients with familial hypercholesterolemia
      (FH) and statin intolerance at very high cardiovascular risk. Recently, studies
      demonstrated the effects of two novel lipid-lowering agents (lomitapide and
      mipomersen) for the management of homozygous FH by decreasing LDL-C values and
      reducing cardiovascular events. However, the costs for these new therapies made
      the cost-effectiveness debate more complicated.

PMID- 29361724
TI  - Supported Zeolite Beta Layers via an Organic Template-Free Preparation Route.
AB  - Layers of high silica zeolites, synthesized with an organic structure directing
      agent (OSDA) and grown onto porous support structures, frequently suffer from the
      thermal stress during the removal of OSDA via the calcination process. The
      different thermal expansion coefficients of the zeolite and the support material,
      especially when stainless steel is used as a support, causes enormous tension
      resulting in defect formation in the zeolite layer. However, the calcination is
      an easy procedure to decompose the OSDA in the pore system of the zeolite.
      Recently, methods to synthesize zeolite beta without the use of an organic
      structure directing agent have been described. In the present study, a seed
      directed synthesis is used to prepare OSDA-free zeolite beta layers on stainless
      steel supports via an in situ preparation route. For the application as membrane,
      a porous stainless steel support has been chosen. The beta/stainless steel
      composites are characterized by X-ray diffraction (XRD) and scanning electron
      microscopy (SEM). To prove its possible application as a membrane, the
      beta/stainless steel composites were also tested by single gas permeances of H2,
      He, CO2, N2, and CH4.

PMID- 29361726
TI  - Preparation of High Mechanical Performance Nano-Fe3O4/Wood Fiber Binderless
      Composite Boards for Electromagnetic Absorption via a Facile and Green Method.
AB  - Fe3O4/wood fiber composites are prepared with a green mechanical method using
      only distilled water as a solvent without any chemical agents, and then a
      binderless composite board with high mechanical properties is obtained via a hot
      press for electromagnetic (EM) absorption. The fibers are connected by hydrogen
      bonds after being mechanically pretreated, and Fe3O4 nanoparticles (NPs) are
      attached to the fiber surface through physical adsorption. The composite board is
      bonded by an adhesive, which is provided by the reaction of fiber composition
      under high temperature and pressure. The Nano-Fe3O4/Fiber (NFF) binderless
      composite board shows remarkable microwave absorption properties and high
      mechanical strength. The optional reflection loss (RL) of the as-prepared
      binderless composite board is -31.90 dB. The bending strength of the NFF
      binderless composite board is 36.36 MPa with the addition of 6% nano-Fe3O4, the
      modulus of elasticity (MOE) is 6842.16 MPa, and the internal bond (IB) strength
      is 0.81 MPa. These results demonstrate that magnetic nanoparticles are deposited
      in binderless composite board by hot pressing, which is the easiest way to
      produce high mechanical strength and EM absorbers.

PMID- 29361728
TI  - Organizational and Occupational Stressors, Their Consequences and Coping
      Strategies: A Questionnaire Survey among Italian Patrol Police Officers.
AB  - Background: Traditionally, workers employed in police forces have been found to
      be exposed to a high risk of distress. Several studies reported that the main
      stressors were associated more with organizational aspects, whilst other
      researchers underlined that the main stressor were associated more with
      operational issues. The aim of this research was to investigate operational and
      organizational stressors, their consequences also in terms of anxiety and the
      coping strategies adopted. Methods: We compared Patrol Police Officers working in
      the Operational Service (Outdoor Patrol Officers) and those in the Interior
      Department (Indoor Patrol Officers) in the same Municipal Police force. Results:
      The results revealed that both Outdoor Patrol Officers and Interior Patrol
      Officers suffered from organizational and occupational stressor. Outdoor Patrol
      Officers appeared more willing to use different coping strategies, whereas Indoor
      Patrol Officers used avoidance strategies. This allows Outdoor Patrol Officers to
      explore new responses and approaches to deal with situations which-owing to the
      type of work-it is impossible to change. Outdoor Patrol Officers appeared better
      equipped to change their attitude to work than Indoor Patrol Officers.
      Conclusion: Interventions on both organizational and operational stressors would
      improve the quality of Patrol Police Officers' working life and have positive
      repercussions on the service offered to the general public.

PMID- 29361727
TI  - Green Synthesis, Characterization and Application of Proanthocyanidins
      Functionalized Gold Nanoparticles.
AB  - Green synthesis of gold nanoparticles using plant extracts is one of the more
      promising approaches for obtaining environmentally friendly nanomaterials for
      biological applications and environmental remediation. In this study,
      proanthocyanidins-functionalized gold nanoparticles were synthesized via a
      hydrothermal method. The obtained gold nanoparticles were characterized by
      ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared
      spectroscopy (FTIR), transmission electron microscopy (TEM) and X-ray diffraction
      (XRD) measurements. UV-Vis and FTIR results indicated that the obtained products
      were mainly spherical in shape, and that the phenolic hydroxyl of
      proanthocyanidins had strong interactions with the gold surface. TEM and XRD
      determination revealed that the synthesized gold nanoparticles had a highly
      crystalline structure and good monodispersity. The application of
      proanthocyanidins-functionalized gold nanoparticles for the removal of dyes and
      heavy metal ions Ni2+, Cu2+, Cd2+ and Pb2+ in an aqueous solution was
      investigated. The primary results indicate that proanthocyanidins-functionalized
      gold nanoparticles had high removal rates for the heavy metal ions and dye, which
      implies that they have potential applications as a new kind of adsorbent for the
      removal of contaminants in aqueous solution.

PMID- 29361729
TI  - Online Removal of Baseline Shift with a Polynomial Function for Hemodynamic
      Monitoring Using Near-Infrared Spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) has become widely accepted as a valuable tool
      for noninvasively monitoring hemodynamics for clinical and diagnostic purposes.
      Baseline shift has attracted great attention in the field, but there has been
      little quantitative study on baseline removal. Here, we aimed to study the
      baseline characteristics of an in-house-built portable medical NIRS device over a
      long time (>3.5 h). We found that the measured baselines all formed perfect
      polynomial functions on phantom tests mimicking human bodies, which were
      identified by recent NIRS studies. More importantly, our study shows that the
      fourth-order polynomial function acted to distinguish performance with stable and
      low-computation-burden fitting calibration (R-square >0.99 for all probes) among
      second- to sixth-order polynomials, evaluated by the parameters R-square, sum of
      squares due to error, and residual. This study provides a straightforward,
      efficient, and quantitatively evaluated solution for online baseline removal for
      hemodynamic monitoring using NIRS devices.

PMID- 29361725
TI  - Chondrosarcoma: A Rare Misfortune in Aging Human Cartilage? The Role of Stem and
      Progenitor Cells in Proliferation, Malignant Degeneration and Therapeutic
      Resistance.
AB  - Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas
      with a peak incidence in adolescents and young adults, conventional and
      dedifferentiated chondrosarcomas mainly affect people in the 4th to 7th decade of
      life. To date, the cell type of chondrosarcoma origin is not clearly defined.
      However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone
      marrow facing a pro-proliferative as well as predominantly chondrogenic
      differentiation milieu, as is implicated in early stage osteoarthritis (OA) at
      that age, are the source of chondrosarcoma genesis. But how can MSPC become
      malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma,
      whereas the incidence of OA is a thousandfold higher. This means a rare
      coincidence of factors allowing escape from senescence and apoptosis together
      with induction of angiogenesis and migration is needed to generate a
      chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an
      intermediate type of tumor which rarely metastasizes. Unfortunately, advanced
      stages show a pronounced resistance both against chemo- and radiation-therapy and
      frequently metastasize. In this review, we elucidate signaling pathways involved
      in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC
      compared to signaling in articular cartilage (AC).

PMID- 29361730
TI  - Deregulation of Frizzled Receptors in Hepatocellular Carcinoma.
AB  - G protein-coupled receptors (GPCRs) have a substantial role in tumorigenesis and
      are described as a "cancer driver". Aberrant expression or activation of GPCRs
      leads to the deregulation of downstream signaling pathways, thereby promoting
      cancer progression. In hepatocellular carcinoma (HCC), the Wnt signaling pathway
      is frequently activated and it is associated with an aggressive HCC phenotype.
      Frizzled (FZD) receptors, a family member of GPCRs, are known to mediate Wnt
      signaling. Accumulating findings have revealed the deregulation of FZD receptors
      in HCC and their functional roles have been implicated in HCC progression. Given
      the important role of FZD receptors in HCC, we summarize here the expression
      pattern of FZD receptors in HCC and their corresponding functional roles during
      HCC progression. We also further review and highlight the potential targeting of
      FZD receptors as an alternative therapeutic strategy in HCC.

PMID- 29361731
TI  - In Vitro Antitumor Activity of Aloperine on Human Thyroid Cancer Cells through
      Caspase-Dependent Apoptosis.
AB  - The global incidence of thyroid cancer, one of the most common endocrine
      malignancies, is especially high among women. Although most patients with thyroid
      cancers exhibit a good prognosis with standard treatment, there are no effective
      therapies for patients with anaplastic thyroid cancers or cancers that have
      reached an advanced or recurrent level. Therefore, it is important to develop
      highly effective compounds for treating such patients. Aloperine, a natural
      compound isolated from Sophora alopecuroides, has been reported to possess
      antioxidant, anti-inflammatory, anti-neuronal injury, anti-renal injury,
      antitumor, anti-allergic, and antiviral properties. In this study, we show that
      aloperine can inhibit cell growth in human anaplastic thyroid cancers and
      multidrug-resistant papillary thyroid cancers. Moreover, it could suppress in
      vitro tumorigenesis and promote cellular apoptosis. Further analysis demonstrated
      the involvement of caspase-dependent apoptosis, including intrinsic and/or
      extrinsic pathways, in aloperine-induced cellular apoptosis. However, cell cycle
      regulation was not detected with aloperine treatment. This study suggests the
      potential therapeutic use of aloperine in human anaplastic thyroid cancers and
      multidrug-resistant papillary thyroid cancers.

PMID- 29361732
TI  - Auricular Neuromodulation: The Emerging Concept beyond the Stimulation of Vagus
      and Trigeminal Nerves.
AB  - Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to
      be the best way to exploit brain plasticity for therapeutic purposes. In the past
      years, there has been tremendous advances in the field of non-pharmacological
      modulation of brain activity. This review of different neurostimulation
      techniques will focus on sites and mechanisms of both transcutaneous vagus and
      trigeminal nerve stimulation. These methods are scientifically validated non
      invasive bottom-up brain modulation techniques, easily implemented from the outer
      ear. In the light of this, auricles could transpire to be the most affordable
      target for non-invasive manipulation of central nervous system functions.

PMID- 29361734
TI  - Influence of Muscle Mass and Outdoor Environmental Factors on Appetite and
      Satiety Feeling in Young Japanese Women.
AB  - Research on the influence of relationships among satiety, muscle mass, and
      outdoor environmental factors is sparse. In this work the relationships among
      satiety feeling, body composition, and outdoor environmental factors on eating in
      healthy young Japanese women are investigated. Fifty three (53) women were
      examined over an approximately 2-year period. All participants ate the same
      lunch; feelings of satiety and body composition were measured before and
      immediately after lunch. Satiety was assessed using a visual analog scale.
      Outdoor environmental factors were recorded at the time of measurement. Results
      showed that satiety before lunch decreased with increased muscle mass and
      decreased humidity (p < 0.05). The Delta satiety increased on eating with
      increased outdoor temperature (p < 0.05). The Delta satiety with high outdoor
      temperature was significantly greater than with low outdoor temperature (p =
      0.005). Decreased muscle mass more influenced Delta satiety with respect to
      outdoor temperature than increased muscle mass (p = 0.007). The results suggest
      that increased muscle mass and decreased humidity increase hunger (unlike
      satiety) before eating. The findings also show that outdoor temperature clearly
      influences the magnitude of satiety on eating. Increasing muscle mass may be
      useful for satiety control at various outdoor temperatures in young women.

PMID- 29361736
TI  - Route and Type of Formulation Administered Influences the Absorption and
      Disposition of Vitamin B12 Levels in Serum.
AB  - The administration of biological compounds that optimize health benefits is an
      ever-evolving therapeutic goal. Pharmaceutical and other adjunctive biological
      compounds have been administered via many different routes in order to produce a
      systemic pharmacological effect. The article summarizes the findings from an
      Australian comparative study in adults administered vitamin B12 through different
      oral delivery platforms. A total of 16 subjects (9 males, 7 females) voluntarily
      partook in a comparative clinical study of five different vitamin B12
      formulations across a six-month period, completing 474 person-hours of cumulative
      contribution, that was equivalent to an n = 60 participation. A nanoparticle
      delivered vitamin B12 through a NanoCelle platform was observed to be
      significantly (p < 0.05) better absorbed than all other dose equivalent platforms
      (i.e., tablets, emulsions, or liposomes) from baseline to 1, 3, and 6 h of the
      study period. The nanoparticle platform delivered vitamin B12 demonstrated an
      enhanced and significant absorption profile as exemplified by rapid systemic
      detection (i.e., 1 h from baseline) when administered to the oro-buccal mucosa
      with no reports of any adverse events of toxicity. The nanoparticle formulation
      of methylcobalamin (1000 ug/dose in 0.3 mL volume) showed bioequivalence only
      with a chewable-dissolvable tablet that administered a five times higher dose of
      methylcobalamin (5000 ug) per tablet. This study has demonstrated that an active
      metabolite embedded in a functional biomaterial (NanoCelle) may constitute a drug
      delivery method that can better access the circulatory system.

PMID- 29361735
TI  - Towards a Novel Class of Multitarget-Directed Ligands: Dual P2X7-NMDA Receptor
      Antagonists.
AB  - Multi-target-directed ligands (MTDLs) offer new hope for the treatment of
      multifactorial complex diseases such as Alzheimer's Disease (AD). Herein, we
      present compounds aimed at targeting the NMDA and the P2X7 receptors, which
      embody a different approach to AD therapy. On one hand, we are seeking to delay
      neurodegeneration targeting the glutamatergic NMDA receptors; on the other hand,
      we also aim to reduce neuroinflammation, targeting P2X7 receptors. Although the
      NMDA receptor is a widely recognized therapeutic target in treating AD, the P2X7
      receptor remains largely unexplored for this purpose; therefore, the dual
      inhibitor presented herein-which is open to further optimization-represents the
      first member of a new class of MTDLs.

PMID- 29361733
TI  - Verdinexor Targeting of CRM1 is a Promising Therapeutic Approach against RSV and
      Influenza Viruses.
AB  - Two primary causes of respiratory tract infections are respiratory syncytial
      virus (RSV) and influenza viruses, both of which remain major public health
      concerns. There are a limited number of antiviral drugs available for the
      treatment of RSV and influenza, each having limited effectiveness and each
      driving selective pressure for the emergence of drug-resistant viruses. Novel
      broad-spectrum antivirals are needed to circumvent problems with current disease
      intervention strategies, while improving the cytokine-induced immunopathology
      associated with RSV and influenza infections. In this review, we examine the use
      of Verdinexor (KPT-335, a novel orally bioavailable drug that functions as a
      selective inhibitor of nuclear export, SINE), as an antiviral with multifaceted
      therapeutic potential. KPT-335 works to (1) block CRM1 (i.e., Chromosome Region
      Maintenance 1; exportin 1 or XPO1) mediated export of viral proteins critical for
      RSV and influenza pathogenesis; and (2) repress nuclear factor kappaB (NF-kappaB)
      activation, thus reducing cytokine production and eliminating virus-associated
      immunopathology. The repurposing of SINE compounds as antivirals shows promise
      not only against RSV and influenza virus but also against other viruses that
      exploit the nucleus as part of their viral life cycle.

PMID- 29361737
TI  - Endothelium-Dependent Hyperpolarization (EDH) in Hypertension: The Role of
      Endothelial Ion Channels.
AB  - Upon stimulation with agonists and shear stress, the vascular endothelium of
      different vessels selectively releases several vasodilator factors such as nitric
      oxide and prostacyclin. In addition, vascular endothelial cells of many vessels
      regulate the contractility of the vascular smooth muscle cells through the
      generation of endothelium-dependent hyperpolarization (EDH). There is a general
      consensus that the opening of small- and intermediate-conductance Ca2+-activated
      K+ channels (SKCa and IKCa) is the initial mechanistic step for the generation of
      EDH. In animal models and humans, EDH and EDH-mediated relaxations are impaired
      during hypertension, and anti-hypertensive treatments restore such impairments.
      However, the underlying mechanisms of reduced EDH and its improvement by lowering
      blood pressure are poorly understood. Emerging evidence suggests that alterations
      of endothelial ion channels such as SKCa channels, inward rectifier K+ channels,
      Ca2+-activated Cl- channels, and transient receptor potential vanilloid type 4
      channels contribute to the impaired EDH during hypertension. In this review, we
      attempt to summarize the accumulating evidence regarding the pathophysiological
      role of endothelial ion channels, focusing on their relationship with EDH during
      hypertension.

PMID- 29361738
TI  - Effects of Exogenous Melatonin on Methyl Viologen-Mediated Oxidative Stress in
      Apple Leaf.
AB  - Oxidative stress is a major source of damage of plants exposed to adverse
      environments. We examined the effect of exogenous melatonin (MT) in limiting of
      oxidative stress caused by methyl viologen (MV; paraquatin) in apple leaves
      (Malus domestica Borkh.). When detached leaves were pre-treated with melatonin,
      their level of stress tolerance increased. Under MV treatment, melatonin
      effectively alleviated the decrease in chlorophyll concentrations and maximum
      potential Photosystem II efficiency while also mitigating membrane damage and
      lipid peroxidation when compared with control leaves that were sprayed only with
      water prior to the stress experiment. The melatonin-treated leaves also showed
      higher activities and transcripts of antioxidant enzymes superoxide dismutase,
      peroxidase, and catalase. In addition, the expression of genes for those enzymes
      was upregulated. Melatonin-synthesis genes MdTDC1, MdT5H4, MdAANAT2, and MdASMT1
      were also upregulated under oxidative stress in leaves but that expression was
      suppressed in response to 1 mM melatonin pretreatment during the MV treatments.
      Therefore, we conclude that exogenous melatonin mitigates the detrimental effects
      of oxidative stress, perhaps by slowing the decline in chlorophyll
      concentrations, moderating membrane damage and lipid peroxidation, increasing the
      activities of antioxidant enzymes, and changing the expression of genes for
      melatonin synthesis.

PMID- 29361740
TI  - Brassicaceae Mustards: Traditional and Agronomic Uses in Australia and New
      Zealand.
AB  - Commonly cultivated Brassicaceae mustards, namely garlic mustard (Alliaria
      petiolata), white mustard (Brassica alba), Ethiopian mustard (B. carinata), Asian
      mustard (B. juncea), oilseed rape (B. napus), black mustard (B. nigra), rapeseed
      (B. rapa), white ball mustard (Calepina irregularis), ball mustard (Neslia
      paniculata), treacle mustard (Erysimum repandum), hedge mustard (Sisymbrium
      officinale), Asian hedge mustard (S. orientale), smooth mustard (S. erysimoides)
      and canola are the major economically important oilseed crops in many countries.
      Mustards were naturalized to Australia and New Zealand and Australia is currently
      the second largest exporter of Brassicaceae oilseeds to meet the global demand
      for a healthy plant-derived oil, high in polyunsaturated fats. Apart from
      providing edible oil, various parts of these plants and many of their
      phytochemicals have been used traditionally for both agronomic as well as
      medicinal purposes, with evidence of their use by early Australian and New
      Zealand settlers and also the indigenous population. This review provides an
      overview of the current knowledge of traditional and agronomic uses of
      Brassicaceae oilseeds and mustards with a focus on their importance in Australia
      and New Zealand.

PMID- 29361742
TI  - A Real-Time Ultraviolet Radiation Imaging System Using an Organic Photoconductive
      Image Sensor.
AB  - We have developed a real time ultraviolet (UV) imaging system that can visualize
      both invisible UV light and a visible (VIS) background scene in an outdoor
      environment. As a UV/VIS image sensor, an organic photoconductive film (OPF)
      imager is employed. The OPF has an intrinsically higher sensitivity in the UV
      wavelength region than those of conventional consumer Complementary Metal Oxide
      Semiconductor (CMOS) image sensors (CIS) or Charge Coupled Devices (CCD). As
      particular examples, imaging of hydrogen flame and of corona discharge is
      demonstrated. UV images overlapped on background scenes are simply made by on
      board background subtraction. The system is capable of imaging weaker UV signals
      by four orders of magnitude than that of VIS background. It is applicable not
      only to future hydrogen supply stations but also to other UV/VIS monitor systems
      requiring UV sensitivity under strong visible radiation environment such as power
      supply substations.

PMID- 29361741
TI  - Chemical Composition, Antimicrobial and Antioxidant Activities of the Flower
      Volatile Oils of Fagopyrum esculentum, Fagopyrum tataricum and Fagopyrum Cymosum.
AB  - The purpose of this study was to investigate the chemical composition and
      biological activity of the volatile oils (VOs) from the flowers of three
      buckwheat species, Fagopyrum esculentum, Fagopyrum tataricum and Fagopyrum
      cymosum. The VOs were obtained from the fresh buckwheat flowers by
      hydrodistillation, and were analyzed for their chemical composition by gas
      chromatography-mass spectrometry (GC-MS). Nonanoic acid (7.58%), (E)-3-hexen-1-ol
      (6.52%), and benzothiazole (5.08%) were the major constituents among the 28
      identified components which accounted for 92.89% of the total oil of F.
      esculentum. 2-Pentadecanone (18.61%), eugenol (17.18%), 1,2-benzenedicarboxylic
      acid, bis(2-methylpropyl) ester (13.19%), and (E,E)-farnesylacetone (7.15%) were
      the major compounds among the 14 identified components which accounted for 88.48%
      of the total oil of F. tataricum. Eugenol (12.22%), (E)-3-hexen-1-yl acetate
      (8.03%), linalool oxide (7.47%), 1-hexanol (7.07%), and benzothiazole (6.72%)
      were the main compounds of the 20 identified components which accounted for
      90.23% of the total oil of F. cymosum. The three VOs were screened to have broad
      spectrum antibacterial activity with minimum inhibitory concentration (MIC)
      values ranged from 100.0 MUg/mL to 800.0 MUg/mL against the tested bacteria, and
      their median inhibitory concentration (IC50) values were from 68.32 MUg/mL to
      452.32 MUg/mL. Xanthomonas vesicatoria was the most sensitive bacterium.
      Moreover, the flower VOs of F. esculentum, F. tataricum and F. cymosum also
      exhibited noteworthy antioxidant capacity with the IC50 value of 354.15 MUg/mL,
      210.63 MUg/mL, and 264.92 MUg/mL for the 1,1-diphenyl-2-picrylhydrazyl (DPPH)
      free radical scavenging assay, and the value of 242.06 MUg/mL, 184.13 MUg/mL, and
      206.11 MUg/mL respectively for the beta-carotene-linoleic bleaching test. These
      results suggested the volatile oils of buckwheat flowers could be potential
      resource of natural antimicrobial and antioxidant agents.

PMID- 29361743
TI  - Microstructure Evolution and Mechanical Properties of Underwater Dry and Local
      Dry Cavity Welded Joints of 690 MPa Grade High Strength Steel.
AB  - Q690E high strength low alloy (HSLA) steel plays an important role in offshore
      structures. In addition, underwater local cavity welding (ULCW) technique was
      widely used to repair important offshore constructions. However, the high cooling
      rate of ULCW joints results in bad welding quality compared with underwater dry
      welding (UDW) joints. Q690E high strength low alloy steels were welded by multi
      pass UDW and ULCW techniques, to study the microstructural evolution and
      mechanical properties of underwater welded joints. The microstructure and
      fracture morphology of welded joints were observed by scanning electron
      microscope and optical microscope. The elemental distribution in the
      microstructure was determined with an Electron Probe Microanalyzer. The results
      indicated that the microstructure of both two welded joints was similar. However,
      martensite and martensite-austenite components were significantly different with
      different underwater welding methods such that the micro-hardness of the HAZ and
      FZ in the ULCW specimen was higher than that of the corresponding regions in UDW
      joint. The yield strength and ultimate tensile strength of the ULCW specimen are
      109 MPa lower and 77 MPa lower, respectively, than those of the UDW joint. The
      impact toughness of the UDW joint was superior to those of the ULCW joint.

PMID- 29361739
TI  - Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus
      Glycoprotein 42 Ligands-Relation to Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown
      etiology, which is characterized by inflammation in the synovium and joint
      damage. Although the pathogenesis of RA remains to be determined, a combination
      of environmental (e.g., viral infections) and genetic factors influence disease
      onset. Especially genetic factors play a vital role in the onset of disease, as
      the heritability of RA is 50-60%, with the human leukocyte antigen (HLA) alleles
      accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles
      encode a conserved sequence of amino acids, referred to as the shared epitope
      (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with
      Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the
      interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry
      factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence
      and, based on several findings, we suggest that EBV is able to induce the onset
      of RA in predisposed SE-positive individuals, by promoting entry of B-cells
      through direct contact between SE and gp42 in the entry complex.

PMID- 29361744
TI  - Dose-Dependent Effects of Green Tea or Mate Extracts on Lipid and Protein
      Oxidation in Brine-Injected Retail-Packed Pork Chops.
AB  - Background: Phenolic plant extracts are added as antioxidants in meat to prevent
      lipid oxidation, but depending on the concentration applied, may affect proteins
      either through covalent interactions or by serving as a prooxidant. Methods:
      Brine-injected pork chops prepared with green tea extract (25-160 ppm gallic acid
      equivalents (GAE)), or mate extract (25-160 ppm GAE) and stored (5  degrees C, 7
      days) in high-oxygen atmosphere packaging (MAP: 80% O2 and 20% CO2) were analyzed
      for color changes, lipid oxidation by thiobarbituric acid reactive substances
      (TBARS), and protein oxidation evaluated by thiol loss and protein radical
      formation by electron spin resonance (ESR) spectroscopy, and compared to a
      control without antioxidant. Results: Extract of mate and green tea showed
      significant and comparable antioxidative effects against formation of TBARS in
      brine-injected pork chops for all concentrations applied compared to the control.
      Protein radical formation decreased significantly by addition of 25 ppm mate
      extract, but increased significantly by addition of 80-160 ppm green tea extract,
      when monitored as formation of protein radicals. Meanwhile, protein thiol groups
      disappeared when applying the extracts by reactions assigned to addition
      reactions of oxidized phenols from the extracts to protein thiols. Conclusion:
      Mate is accordingly a good source of antioxidants for protection of both lipids
      and proteins in brine-injected pork chops chill-stored in high-oxygen atmosphere,
      though the dose must be carefully selected.

PMID- 29361746
TI  - The Enhanced Catalytic Performance and Stability of Rh/gamma-Al2O3 Catalyst
      Synthesized by Atomic Layer Deposition (ALD) for Methane Dry Reforming.
AB  - Rh/gamma-Al2O3 catalysts were synthesized by both incipient wetness impregnation
      (IWI) and atomic layer deposition (ALD). The TEM images of the two catalysts
      showed that the catalyst from ALD had smaller particle size, and narrower size
      distribution. The surface chemical states of both catalysts were investigated by
      both XPS and X-ray Absorption Near Edge Structure (XANES), and the catalyst from
      IWI had higher concentration of Rh3+ than that from ALD. The catalytic
      performance of both catalysts was tested in the dry reforming of methane
      reaction. The catalyst from ALD showed a higher conversion and selectivity than
      that from IWI. The stability testing results indicated that the catalyst from ALD
      showed similar stability to that from IWI at 500  degrees C, but higher stability
      at 800  degrees C.

PMID- 29361745
TI  - Microglia and Aging: The Role of the TREM2-DAP12 and CX3CL1-CX3CR1 Axes.
AB  - Depending on the species, microglial cells represent 5-20% of glial cells in the
      adult brain. As the innate immune effector of the brain, microglia are involved
      in several functions: regulation of inflammation, synaptic connectivity,
      programmed cell death, wiring and circuitry formation, phagocytosis of cell
      debris, and synaptic pruning and sculpting of postnatal neural circuits.
      Moreover, microglia contribute to some neurodevelopmental disorders such as Nasu
      Hakola disease (NHD), and to aged-associated neurodegenerative diseases, such as
      Alzheimer's disease (AD), Parkinson's disease (PD), and others. There is evidence
      that human and rodent microglia may become senescent. This event determines
      alterations in the microglia activation status, associated with a chronic
      inflammation phenotype and with the loss of neuroprotective functions that lead
      to a greater susceptibility to the neurodegenerative diseases of aging. In the
      central nervous system (CNS), Triggering Receptor Expressed on Myeloid Cells 2
      DNAX activation protein 12 (TREM2-DAP12) is a signaling complex expressed
      exclusively in microglia. As a microglial surface receptor, TREM2 interacts with
      DAP12 to initiate signal transduction pathways that promote microglial cell
      activation, phagocytosis, and microglial cell survival. Defective TREM2-DAP12
      functions play a central role in the pathogenesis of several diseases. The CX3CL1
      (fractalkine)-CX3CR1 signaling represents the most important communication
      channel between neurons and microglia. The expression of CX3CL1 in neurons and of
      its receptor CX3CR1 in microglia determines a specific interaction, playing
      fundamental roles in the regulation of the maturation and function of these
      cells. Here, we review the role of the TREM2-DAP12 and CX3CL1-CX3CR1 axes in aged
      microglia and the involvement of these pathways in physiological CNS aging and in
      age-associated neurodegenerative diseases.

PMID- 29361747
TI  - Hereditary Fibrinogen Aalpha-Chain Amyloidosis in Asia: Clinical and Molecular
      Characteristics.
AB  - Hereditary fibrinogen Aalpha-chain amyloidosis (Aalpha-chain amyloidosis) is a
      type of autosomal dominant systemic amyloidosis caused by mutations in fibrinogen
      Aalpha-chain gene (FGA). Patients with Aalpha-chain amyloidosis have been mainly
      reported in Western countries but have been rarely reported in Asia, with only
      five patients with Aalpha-chain amyloidosis being reported in Korea, China, and
      Japan. Clinically, the most prominent manifestation in Asian patients with Aalpha
      chain amyloidosis is progressive nephropathy caused by excessive amyloid
      deposition in the glomeruli, which is similar to that observed in patients with
      Aalpha-chain amyloidosis in Western countries. In molecular features in Asian
      Aalpha-chain amyloidosis, the most common variant, E526V, was found in only one
      Chinese kindred, and other four kindred each had a different variant, which have
      not been identified in other countries. These variants are located in the C
      terminal region (amino acid residues 517-555) of mature Aalpha-chain, which was
      similar to that observed in patients with Aalpha-chain amyloidosis in other
      countries. The precise number of Asian patients with Aalpha-chain amyloidosis is
      unclear. However, patients with Aalpha-chain amyloidosis do exist in Asian
      countries, and the majority of these patients may be diagnosed with other types
      of systemic amyloidosis.

PMID- 29361748
TI  - Perspectives on Current Challenges and Opportunities for Bovine Viral Diarrhoea
      Virus Eradication in Australia and New Zealand.
AB  - This review outlines the history of bovine viral diarrhoea virus (BVDV) and the
      current situation in Australia and New Zealand. BVDV has been reported as present
      in cattle from both countries for close to 60 years. It rates as the second most
      economically significant disease afflicting cattle, and is highly prevalent and
      spread throughout the beef and dairy industries. While other cattle diseases have
      been the subject of government control and eradication, infection with BVDV is
      presently not. Eradication has been undertaken in many other countries and been
      judged to be a good investment, resulting in positive economic returns.
      Presently, Australia and New Zealand have adopted a non-compulsory approach to
      control schemes, initiated and managed by farmers and veterinarians without the
      ultimate goal of eradication. Moving towards eradication is possible with the
      infrastructure both countries possess, but will require additional resources,
      coordination, and funding from stakeholders to move to full eradication.

PMID- 29361750
TI  - An Exploratory Study of Student Pharmacists' Self-Reported Pain, Management
      Strategies, Outcomes, and Implications for Pharmacy Education.
AB  - The objective of this study was to describe the prevalence, management
      strategies, and outcomes of pain experienced by student pharmacists, and to
      discuss implications for pharmacy education. A questionnaire administered to
      student pharmacists collected data about their experience, management strategies,
      and outcomes of pain. Data were analyzed using t-tests, chi-square or Fisher's
      tests, and logistic regression. Of the 218 student pharmacists who completed the
      survey, 79% experienced pain in the past five years. Chronic pain impacted
      students' ability to work (15%) and attend school (9%). Respondents most commonly
      used prescription (38%) and over-the-counter (OTC, 78%) non-steroidal anti
      inflammatory drugs (NSAIDs), and rest (69%) to manage pain. Men used more
      opioids, whereas women used more OTC NSAIDs (p < 0.05). Emergency department
      visits were associated with increased prescription drug use to manage pain. This
      study found that 15% of student pharmacists had chronic pain in the past five
      years, which was managed with medical and non-medical strategies.

PMID- 29361749
TI  - Affinity Purification and Comparative Biosensor Analysis of Citrulline-Peptide
      Specific Antibodies in Rheumatoid Arthritis.
AB  - BACKGROUND: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide
      antibodies (ACPAs) are responsible for disease onset and progression, however,
      our knowledge is limited on ligand binding affinities of autoantibodies with
      different citrulline-peptide specificity. METHODS: Citrulline-peptide-specific
      ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA
      IgGs and serum antibodies were compared by surface plasmon resonance (SPR)
      analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide
      and a complement-activating peptide were used to induce selective depletion of
      ACPA-producing B cells. RESULTS: KD values of affinity-purified ACPA IgGs varied
      between 10-6 and 10-8 M and inversely correlated with disease activity. Based on
      their cross-reaction with citrulline-peptides, we designed a novel multi-epitope
      peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with
      a short, neutral spacer. This peptide detected antibodies in RA sera with 66%
      sensitivity and 98% specificity in ELISA and was recognized by 90% of RA sera,
      while none of the healthy samples in SPR. When coupled to nanoparticles, the
      multi-epitope peptide specifically targeted and depleted ACPA-producing B cells
      ex vivo. CONCLUSIONS: The unique multi-epitope peptide designed based on ACPA
      cross-reactivity might be suitable to develop better diagnostics and novel
      therapies for RA.

PMID- 29361751
TI  - Identification of a Rare Germline Heterozygous Deletion Involving the
      Polycistronic miR-17-92 Cluster in Two First-Degree Relatives from a BRCA 1/2
      Negative Chilean Family with Familial Breast Cancer: Possible Functional
      Implications.
AB  - Micro-RNAs (miRNAs) have emerged as novel gene expression regulators. Recent
      evidence strongly suggests a role for miRNAs in a large variety of cancer-related
      pathways. Different studies have shown that 18.7 to 37% of all human miRNA genes
      are clustered. miR-17-92 polycistronic cluster overexpression is associated with
      human hematolymphoid and solid malignancies including breast cancer (BC). Here,
      we report the identification of rs770419845, a rare 6 bp deletion located within
      the polycistronic miR-17-92 cluster, in two first-degree relatives from a Chilean
      family with familial BC and negative for point mutations in BRCA 1/2 genes. The
      deletion was identified by Sanger sequencing when 99 BRCA1/2 mutation-negative BC
      cases with a strong family history were initially screened. In silico analysis
      predicts that rs770419845 affects the secondary structure and stability of the
      pre-miR-17-pre-miR-18 region and the entire 17-92 cluster. The deletion was
      screened in 458 high-risk BRCA1/2-negative Chilean families and 480 controls.
      rs770419845 was not detected in any control but identified in a single family
      with two cases of BC and other cancers. Both BC cases, the mother and her
      daughter, carried the deletion. Based on bioinformatic analyses, the location of
      the deletion and its low frequency, we presume rs770419845 may be a pathogenic
      variant. Functional studies are needed to support this hypothesis.

PMID- 29361753
TI  - Deep Brain Stimulation-Possible Treatment Strategy for Pathologically Altered
      Body Weight?
AB  - The treatment of obesity and eating disorders such as binge-eating disorder or
      anorexia nervosa is challenging. Besides lifestyle changes and pharmacological
      options, bariatric surgery represents a well-established and effective-albeit
      invasive-treatment of obesity, whereas for binge-eating disorder and anorexia
      nervosa mostly psychotherapy options exist. Deep brain stimulation (DBS), a
      method that influences the neuronal network, is by now known for its safe and
      effective applicability in patients with Parkinson's disease. However, the use
      does not seem to be restricted to these patients. Recent preclinical and first
      clinical evidence points towards the use of DBS in patients with obesity and
      eating disorders as well. Depending on the targeted area in the brain, DBS can
      either inhibit food intake and body weight or stimulate energy intake and
      subsequently body weight. The current review focuses on preclinical and clinical
      evidence of DBS to modulate food intake and body weight and highlight the
      different brain areas targeted, stimulation protocols applied and downstream
      signaling modulated. Lastly, this review will also critically discuss potential
      safety issues and gaps in knowledge to promote further studies.

PMID- 29361752
TI  - CRISPR/Cas9-Advancing Orthopoxvirus Genome Editing for Vaccine and Vector
      Development.
AB  - The clustered regularly interspaced short palindromic repeat (CRISPR)/associated
      protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its
      high efficiency, specificity, versatility, flexibility, simplicity and low cost
      have made the CRISPR/Cas9 system preferable to other guided site-specific
      nuclease-based systems such as TALENs (Transcription Activator-like Effector
      Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses.
      CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing
      virus infections, eradicating proviral DNA, and inhibiting viral replication in
      infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of
      Vaccinia virus paves the way for its application in editing other vaccine/vector
      relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve
      some of the major hindrances to the development of OPXV-based recombinant
      vaccines and vectors, including sub-optimal immunogenicity; transgene and genome
      instability; reversion of attenuation; potential of spread of transgenes to
      wildtype strains and close contacts, which are important biosafety and risk
      assessment considerations. In this article, we review the published literature on
      the application of CRISPR/Cas9 in virus genome editing and discuss the potentials
      of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also
      discuss the application of CRISPR/Cas9 in combating viruses of clinical
      relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome
      them.

PMID- 29361756
TI  - One-Step Preparation of Large Area Films of Oriented MoS2 Nanoparticles on
      Multilayer Graphene and Its Electrocatalytic Activity for Hydrogen Evolution.
AB  - MoS2 is a promising material to replace Pt-based catalysts for the hydrogen
      evolution reaction (HER), due to its excellent stability and high activity. In
      this work, MoS2 nanoparticles supported on graphitic carbon (about 20 nm) with a
      preferential 002 facet orientation have been prepared by pyrolysis of alginic
      acid films on quartz containing adsorbed (NH4)2MoS4 at 900  degrees C under Ar
      atmosphere. Although some variation of the electrocatalytic activity has been
      observed from batch to batch, the MoS2 sample exhibited activity for HER (a
      potential onset between 0.2 and 0.3 V vs. SCE), depending on the concentrations
      of (NH4)2MoS4 precursor used in the preparation process. The loading and particle
      size of MoS2, which correlate with the amount of exposed active sites in the
      sample, are the main factors influencing the electrocatalytic activity.

PMID- 29361754
TI  - Advanced Material Strategies for Next-Generation Additive Manufacturing.
AB  - Additive manufacturing (AM) has drawn tremendous attention in various fields. In
      recent years, great efforts have been made to develop novel additive
      manufacturing processes such as micro-/nano-scale 3D printing, bioprinting, and
      4D printing for the fabrication of complex 3D structures with high resolution,
      living components, and multimaterials. The development of advanced functional
      materials is important for the implementation of these novel additive
      manufacturing processes. Here, a state-of-the-art review on advanced material
      strategies for novel additive manufacturing processes is provided, mainly
      including conductive materials, biomaterials, and smart materials. The
      advantages, limitations, and future perspectives of these materials for additive
      manufacturing are discussed. It is believed that the innovations of material
      strategies in parallel with the evolution of additive manufacturing processes
      will provide numerous possibilities for the fabrication of complex smart
      constructs with multiple functions, which will significantly widen the
      application fields of next-generation additive manufacturing.

PMID- 29361757
TI  - Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck
      Cancer: Potential Utility as Biomarkers for Prognosis.
AB  - Clarifying the epigenetic regulation of tumor-related genes (TRGs) can provide
      insights into the mechanisms of tumorigenesis and the risk for disease recurrence
      in HPV-negative head and neck cancers, originating in the hypopharynx, larynx,
      and oral cavity. We analyzed the methylation status of the promoters of 30 TRGs
      in 178 HPV-negative head and neck cancer patients using a quantitative
      methylation-specific PCR. Promoter methylation was correlated with various
      clinical characteristics and patient survival. The mean number of methylated TRGs
      was 14.2 (range, 2-25). In the multivariate Cox proportional hazards analysis,
      the methylation of COL1A2 and VEGFR1 was associated with poor survival for
      hypopharyngeal cancer, with hazard ratios: 3.19; p = 0.009 and 3.07; p = 0.014,
      respectively. The methylation of p16 and COL1A2 were independent prognostic
      factors for poor survival in laryngeal cancer (hazard ratio: 4.55; p = 0.013 and
      3.12; p = 0.035, respectively). In patients with oral cancer, the methylation of
      TAC1 and SSTR1 best correlated with poor survival (hazard ratio: 4.29; p = 0.005
      and 5.38; p = 0.029, respectively). Our findings suggest that methylation status
      of TRGs could serve as important site-specific biomarkers for prediction of
      clinical outcomes in patients with HPV-negative head and neck cancer.

PMID- 29361758
TI  - Effect of Aspect Ratio on the Permittivity of Graphite Fiber in Microwave
      Heating.
AB  - Microwave (MW) heating has received attention as a new heating source for various
      industrial processes. Some materials are expected to be a more effective absorber
      of MW, and graphite is observed as a possible candidate for high-temperature
      application. We investigated the dependence of the aspect ratio of graphite
      fibers on both their heating behavior and permittivity under a 2.45 GHz MW
      electric field. In these experiments, both loss tangent and MW heating behavior
      indicated that the MW absorption of conductive fibers increases with their aspect
      ratio. The MW absorption was found to be well accounted for by the application of
      a spheroidal model for a single fiber. The absorption of graphite fibers
      decreases with increasing aspect ratio when the long axis of the ellipsoid is
      perpendicular to the electric field, whereas it increases with the aspect ratio
      when the long axis is parallel to the electric field. The analytical model
      indicated that MW heating of the conductive fibers is expected to depend on both
      the shape and arrangement of the fibers in the electric field.

PMID- 29361760
TI  - Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested
      Implications.
AB  - Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics
      than in genetic epidemiology, although associations between Y-DNA haplogroups and
      several traits, including cardiometabolic traits, have been reported. In
      apparently homogeneous populations defined by principal component analyses, there
      is still Y-DNA haplogroup variation which will result from population history.
      Therefore, hidden stratification and/or differential phenotypic effects by Y-DNA
      haplogroups could exist. To test this, we hypothesised that stratifying
      individuals according to their Y-DNA haplogroups before testing for associations
      between autosomal single nucleotide polymorphisms (SNPs) and phenotypes will
      yield difference in association. For proof of concept, we derived Y-DNA
      haplogroups from 6537 males from two epidemiological cohorts, Avon Longitudinal
      Study of Parents and Children (ALSPAC) (n = 5080; 816 Y-DNA SNPs) and the 1958
      Birth Cohort (n = 1457; 1849 Y-DNA SNPs), and studied the robust associations
      between 32 SNPs and body mass index (BMI), including SNPs in or near Fat Mass and
      Obesity-associated protein (FTO) which yield the strongest effects. Overall, no
      association was replicated in both cohorts when Y-DNA haplogroups were considered
      and this suggests that, for BMI at least, there is little evidence of differences
      in phenotype or SNP association by Y-DNA structure. Further studies using other
      traits, phenome-wide association studies (PheWAS), other haplogroups and/or
      autosomal SNPs are required to test the generalisability and utility of this
      approach.

PMID- 29361761
TI  - Social and Environmental Influences on Physical Activity Behaviours.
AB  - Physical activity promotion has met with limited success across a range of
      demographic indicators, largely due to our poor understanding of how drivers of
      physical activity behaviours vary by context and setting[...].

PMID- 29361762
TI  - West Nile Virus and Usutu Virus Monitoring of Wild Birds in Germany.
AB  - By systematically setting up a unique nation-wide wild bird surveillance network,
      we monitored migratory and resident birds for zoonotic arthropod-borne virus
      infections, such as the flaviviruses West Nile virus (WNV) and Usutu virus
      (USUV). More than 1900 wild bird blood samples, from 20 orders and 136 different
      bird species, were collected between 2014 and 2016. Samples were investigated by
      WNV and USUV-specific real-time polymerase chain reactions as well as by
      differentiating virus neutralization tests. Dead bird surveillance data, obtained
      from organ investigations in 2016, were also included. WNV-specific RNA was not
      detected, whereas four wild bird blood samples tested positive for USUV-specific
      RNA. Additionally, 73 USUV-positive birds were detected in the 2016 dead bird
      surveillance. WNV neutralizing antibodies were predominantly found in long
      distance, partial and short-distance migrants, while USUV neutralizing antibodies
      were mainly detected in resident wild bird species, preferentially with low
      seroprevalences. To date, WNV-specific RNA has neither been detected in wild
      birds, nor in mosquitoes, thus, we conclude that WNV is not yet present in
      Germany. Continued wild bird and mosquito monitoring studies are essential to
      detect the incursion of zoonotic viruses and to allow risk assessments for
      zoonotic pathogens.

PMID- 29361763
TI  - Fe-Doped Sol-Gel Glasses and Glass-Ceramics for Magnetic Hyperthermia.
AB  - This work deals with the synthesis and characterization of novel Fe-containing
      sol-gel materials obtained by modifying the composition of a binary SiO2-CaO
      parent glass with the addition of Fe2O3. The effect of different processing
      conditions (calcination in air vs. argon flowing) on the formation of magnetic
      crystalline phases was investigated. The produced materials were analyzed from
      thermal (hot-stage microscopy, differential thermal analysis, and differential
      thermal calorimetry) and microstructural (X-ray diffraction) viewpoints to assess
      both the behavior upon heating and the development of crystalline phases. N2
      adsorption-desorption measurements allowed determining that these materials have
      high surface area (40-120 m2/g) and mesoporous texture with mesopore size in the
      range of 18 to 30 nm. It was assessed that the magnetic properties can actually
      be tailored by controlling the Fe content and the environmental conditions
      (oxidant vs. inert atmosphere) during calcination. The glasses and glass-ceramics
      developed in this work show promise for applications in bone tissue healing which
      require the use of biocompatible magnetic implants able to elicit therapeutic
      actions, such as hyperthermia for bone cancer treatment.

PMID- 29361764
TI  - HnRNPA1 Specifically Recognizes the Base of Nucleotide at the Loop of RNA G
      Quadruplex.
AB  - Human telomere RNA performs various cellular functions, such as telomere length
      regulation, heterochromatin formation, and end protection. We recently
      demonstrated that the loops in the RNA G-quadruplex are important in the
      interaction of telomere RNA with heterogeneous nuclear ribonucleoprotein A1
      (hnRNPA1). Here, we report on a detailed analysis of hnRNPA1 binding to telomere
      RNA G-quadruplexes with a group of loop variants using an electrophoretic
      mobility shift assay (EMSA) and circular dichroism (CD) spectroscopy. We found
      that the hnRNPA1 binds to RNA G-quadruplexes with the 2'-O-methyl and DNA loops,
      but fails to bind with the abasic RNA and DNA loops. These results suggested that
      hnRNPA1 binds to the loop of the RNA G-quadruplex by recognizing the base of the
      loop's nucleotides. The observation provides the first evidence that the base of
      the loop's nucleotides is a key factor for hnRNPA1 specifically recognizing the
      RNA G-quadruplex.

PMID- 29361765
TI  - Tamm-Horsfall Protein is a Potent Immunomodulatory Molecule and a Disease
      Biomarker in the Urinary System.
AB  - Tamm-Horsfall protein (THP), or uromodulin (UMOD), is an 80-90-kDa
      phosphatidylinositol-anchored glycoprotein produced exclusively by the renal
      tubular cells in the thick ascending limb of the loop of Henle. Physiologically,
      THP is implicated in renal countercurrent gradient formation, sodium homeostasis,
      blood pressure regulation, and a defense molecule against infections in the
      urinary system. Investigations have also revealed that THP is an effective
      binding ligand for serum albumin, immunoglobulin G light chains, complement
      components C1 and C1q, interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor
      (TNF)-alpha, and interferon-gamma through its carbohydrate side chains for
      maintaining circulatory and renal immune homeostasis. Thus, THP can be regarded
      as part of the innate immune system. UMOD mutations play crucial roles in
      congenital urolithiasis, hereditary hyperuricemia/gout, and medullary cystic
      kidney diseases. Recent investigations have focused on the immunomodulatory
      effects of THP on immune cells and on THP as a disease biomarker of acute and
      chronic kidney diseases. Our studies have suggested that normal urinary THP,
      through its epidermal growth factor (EGF)-like domains, binds to the surface
      expressed EGF-like receptors, cathepsin G, or lactoferrin to enhance
      polymorphonuclear leukocyte phagocytosis, proinflammatory cytokine production by
      monocytes/macrophages, and lymphocyte proliferation by activating the Rho family
      and mitogen-activated protein kinase signaling pathways. Furthermore, our data
      support both an intact protein core structure and carbohydrate side chains are
      important for the different protein-binding capacities of THP. Prospectively,
      parts of the whole THP molecule may be used for anti-TNF-alpha therapy in
      inflammatory diseases, autoantibody-depleting therapy in autoimmune disorders,
      and immune intensification in immunocompromised hosts.

PMID- 29361767
TI  - Electrochemical Behaviour and Galvanic Effects of Titanium Implants Coupled to
      Metallic Suprastructures in Artificial Saliva.
AB  - The aim of the present study is to analyze the electrochemical behavior of five
      different dental alloys: two cobalt-chromium alloys (CoCr and CoCr-c), one nickel
      chromium-titanium alloy (NiCrTi), one gold-palladium alloy (Au), and one titanium
      alloy (Ti6Al4V), and the galvanic effect when they are coupled to titanium
      implants (TiG2). It was carried out by electrochemical techniques (open circuit
      measurements, potentiodynamic curves and Zero-Resistance Ammetry) in artificial
      saliva (AS), with and without fluorides in different acidic conditions. The
      studied alloys are spontaneously passivated, but NiCrTi alloy has a very narrow
      passive domain and losses its passivity in presence of fluorides, so is not
      considered as a good option for implant superstructures. Variations of pH from
      6.5 to 3 in artificial saliva do not change the electrochemical behavior of Ti,
      Ti6Al4V, and CoCr alloys, and couples, but when the pH of the artificial saliva
      is below 3.5 and the fluoride content is 1000 ppm Ti and Ti6Al4V starts actively
      dissolving, and CoCr-c superstructures coupled to Ti show acceleration of
      corrosion due to galvanic effects. Thus, NiCrTi is not recommended for implant
      superstructures because of risk of Ni ion release to the body, and fluorides
      should be avoided in acidic media because Ti, Ti6Al4V, and CoCr-c superstructures
      show galvanic corrosion. The best combinations are Ti/Ti6Al4V and Ti/CoCr as
      alternative of noble gold alloys.

PMID- 29361766
TI  - Carbohydrate Counting in Children and Adolescents with Type 1 Diabetes.
AB  - Carbohydrate counting (CC) is a meal-planning tool for patients with type 1
      diabetes (T1D) treated with a basal bolus insulin regimen by means of multiple
      daily injections or continuous subcutaneous insulin infusion. It is based on an
      awareness of foods that contain carbohydrates and their effect on blood glucose.
      The bolus insulin dose needed is obtained from the total amount of carbohydrates
      consumed at each meal and the insulin-to-carbohydrate ratio. Evidence suggests
      that CC may have positive effects on metabolic control and on reducing
      glycosylated haemoglobin concentration (HbA1c). Moreover, CC might reduce the
      frequency of hypoglycaemia. In addition, with CC the flexibility of meals and
      snacks allows children and teenagers to manage their T1D more effectively within
      their own lifestyles. CC and the bolus calculator can have possible beneficial
      effects in improving post-meal glucose, with a higher percentage of values within
      the target. Moreover, CC might be integrated with the counting of fat and protein
      to more accurately calculate the insulin bolus. In conclusion, in children and
      adolescents with T1D, CC may have a positive effect on metabolic control, might
      reduce hypoglycaemia events, improves quality of life, and seems to do so without
      influencing body mass index; however, more high-quality clinical trials are
      needed to confirm this positive impact.

PMID- 29361768
TI  - A Rapid Method for the Determination of Fucoxanthin in Diatom.
AB  - Fucoxanthin is a natural pigment found in microalgae, especially diatoms and
      Chrysophyta. Recently, it has been shown to have anti-inflammatory, anti-tumor,
      and anti-obesityactivity in humans. Phaeodactylum tricornutum is a diatom with
      high economic potential due to its high content of fucoxanthin and
      eicosapentaenoic acid. In order to improve fucoxanthin production, physical and
      chemical mutagenesis could be applied to generate mutants. An accurate and rapid
      method to assess the fucoxanthin content is a prerequisite for a high-throughput
      screen of mutants. In this work, the content of fucoxanthin in P. tricornutum was
      determined using spectrophotometry instead of high performance liquid
      chromatography (HPLC). This spectrophotometric method is easier and faster than
      liquid chromatography and the standard error was less than 5% when compared to
      the HPLC results. Also, this method can be applied to other diatoms, with
      standard errors of 3-14.6%. It provides a high throughput screening method for
      microalgae strains producing fucoxanthin.

PMID- 29361769
TI  - The Location of Conjunctivochalasis and Its Clinical Correlation with the
      Severity of Dry Eye Symptoms.
AB  - Background: We aimed to investigate the clinical importance of
      conjunctivochalasis (CCH) and, further, to implement a new CCH classification
      system. Methods: 60 eyes of patients with whom, upon clinical examination, CCH
      was diagnosed were investigated for the presence of symptoms and signs
      characteristic of dry eye. The eyes were grouped based on two stages of severity,
      Stage 1 (minimal/mild) and Stage 2 (medium/severe), for each nasal, middle, and
      temporal position, and on the extent of CCH folds in each site. Results: In 40
      (66.6%) out of 60 eyes, symptoms and signs of CCH were manifest: pain in 25
      (41.6%), epiphora in 25 (41.6%), and lacrimal punctum obstruction from
      conjunctival folds in 22 (36.6%) eyes. Depending on the position of CCH, a
      greater percentage of symptoms appeared in Stage 2 in the nasal position (78.9%),
      followed by middle (68.7%) and temporal positions (60%). When TBUT values were
      compared, statistically significant differences were found proportional to
      grading (p < 0.001) and position (nasal more severe than temporal, p < 0.001),
      and such differences were also found when TBUT values of all eyes were compared
      with those of symptomatic eyes (p = 0.01) and with those of symptom-free eyes (p
      = 0.002). Conclusions: CCH is a rather frequent and commonly unrecognized
      condition that should always be considered in differential diagnoses of dry eye.

PMID- 29361770
TI  - Chemical Constituents from Apios americana and Their Inhibitory Activity on
      Tyrosinase.
AB  - The goal of this study was to identify phytochemicals with inhibitory activity
      against tyrosinase. Nine compounds 1-9 were isolated from the tubers of Apios
      americana. This is the first report of aromadendrin 5-methyl ether (1) being
      isolated from the Apios species. Among them, compounds 2 and 8 showed inhibitory
      activity toward tyrosinase. Based on a Dixon plot, the potential Ki values of
      competitive inhibitors 2 and 8 were calculated as 10.3 +/- 0.8 uM and 44.2 +/-
      1.7 uM, respectively. An IC50 value of 13.2 +/- 1.0 uM was calculated for the
      slow-binding inhibitor 2 after preincubation with tyrosinase. Additionally, the
      predicted binding sites between the receptor and ligand, as well as secondary
      structure changes, in the presence of 2 were examined by molecular simulation.

PMID- 29361771
TI  - One-Pot Syntesis of 3-Functionalized 4-Hydroxycoumarin under Catalyst-Free
      Conditions.
AB  - A concise and efficient one-pot synthesis of 3-functionalized 4-hydroxycoumarin
      derivatives via a three-component domino reaction of 4-hydroxycoumarin,
      phenylglyoxal and 3-arylaminocyclopent-2-enone or 4-arylaminofuran-2(5H)-one
      under catalyst-free and microwave irradiation conditions is described. This
      synthesis involves a group-assisted purification process, which avoids
      traditional recrystallization and chromatographic purification methods.

PMID- 29361772
TI  - A Survey of Data Semantization in Internet of Things.
AB  - With the development of Internet of Things (IoT), more and more sensors,
      actuators and mobile devices have been deployed into our daily lives. The result
      is that tremendous data are produced and it is urgent to dig out hidden
      information behind these volumous data. However, IoT data generated by multi
      modal sensors or devices show great differences in formats, domains and types,
      which poses challenges for machines to process and understand. Therefore, adding
      semantics to Internet of Things becomes an overwhelming tendency. This paper
      provides a systematic review of data semantization in IoT, including its
      backgrounds, processing flows, prevalent techniques, applications, existing
      challenges and open issues. It surveys development status of adding semantics to
      IoT data, mainly referring to sensor data and points out current issues and
      challenges that are worth further study.

PMID- 29361773
TI  - Zika Virus Fatally Infects Wild Type Neonatal Mice and Replicates in Central
      Nervous System.
AB  - Zika virus (ZIKV) has been defined as a teratogenic pathogen behind the increased
      number of cases of microcephaly in French Polynesia, Brazil, Puerto Rico, and
      other South American countries. Experimental studies using animal models have
      achieved tremendous insight into understanding the viral pathogenesis,
      transmission, teratogenic mechanisms, and virus-host interactions. However, the
      animals used in published investigations are mostly interferon (IFN)-compromised,
      either genetically or via antibody treatment. Herein, we studied ZIKV infection
      in IFN-competent mice using African (MR766) and Asian strains (PRVABC59 and SZ
      WIV01). After testing four different species of mice, we found that BALB/c
      neonatal mice were resistant to ZIKV infection, that Kunming, ICR and C57BL/6
      neonatal mice were fatally susceptible to ZIKV infection, and that the fatality
      of C57BL/6 neonates from 1 to 3 days old were in a viral dose-dependent manner.
      The size and weight of the brain were significantly reduced, and the ZIKV
      infected mice showed neuronal symptoms such as hind-limb paralysis, tremor, and
      poor balance during walking. Pathologic and immunofluorescent experiments
      revealed that ZIKV infected different areas of the central nervous system (CNS)
      including gray matter, hippocampus, cerebral cortex, and spinal cord, but not
      olfactory bulb. Interestingly, ZIKV replicated in multiple organs and resulted in
      pathogenesis in liver and testis, implying that ZIKV infection may engender a
      high health risk in neonates by postnatal infection. In summary, we investigated
      ZIKV pathogenesis using an animal model that is not IFN-compromised.

PMID- 29361775
TI  - Voltammetric Response of Alizarin Red S-Confined Film-Coated Electrodes to Diol
      and Polyol Compounds: Use of Phenylboronic Acid-Modified Poly(ethyleneimine) as
      Film Component.
AB  - Alizarin red S (ARS) was confined in layer-by-layer (LbL) films composed of
      phenylboronic acid-modified poly(ethyleneimine) (PBA-PEI) and
      carboxymethylcellulose (CMC) to study the voltammetric response to diol and
      polyol compounds. The LbL film-coated gold (Au) electrode and quartz slide were
      immersed in an ARS solution to uptake ARS into the film. UV-visible absorption
      spectra of ARS-confined LbL film suggested that ARS formed boronate ester (ARS
      PBS) in the film. The cyclic voltammetry of the ARS-confined LbL film-coated
      electrodes exhibited oxidation peaks at -0.50 and -0.62 V, which were ascribed to
      the oxidation reactions of ARS-PBS and free ARS, respectively, in the LbL film.
      The peak current at -0.62 V increased upon the addition of diol or polyol
      compounds such as L-dopa, glucose, and sorbitol into the solution, depending on
      the concentration, whereas the peak current at -0.50 V decreased. The results
      suggest a possible use of ARS-confined PBA-PEI/CMC LbL film-coated Au electrodes
      for the construction of voltammetric sensors for diol and polyol compounds.

PMID- 29361774
TI  - The IFNG rs1861494 Single Nucleotide Polymorphism Is Associated with Protection
      against Tuberculosis Disease in Argentina.
AB  - Interferon gamma (IFNG) plays a key role during Mycobacterium tuberculosis (Mtb)
      infection, and several polymorphisms located in its gene are associated with risk
      of tuberculosis in diverse populations. Nevertheless, the genetic
      resistance/susceptibility to tuberculosis in Argentina is unknown. The IFNG
      rs1861494 polymorphism (G->A) was reported to alter the binding of transcription
      factors to this region, influencing IFNG production. Using a case-control study,
      we found an association between the AA and AG genotypes and tuberculosis
      resistance (AA vs. GG: odds ratio (OR) = 0.235, p-value = 0.012; AG vs. GG: OR =
      0.303, p-value = 0.044; AA vs. AG: OR = 0.776, p-value = 0.427; AA + AG vs. GG:
      OR = 0.270, p-value = 0.022). Moreover, Mtb-antigen stimulated peripheral blood
      mononuclear cells (PBMCs) from healthy donors and AA carriers secreted the
      highest amounts of IFNG in culture supernatants (p-value = 0.034) and presented
      the greatest percentage of CD4+IFNG+ lymphocytes (p-value = 0.035), in comparison
      with GG carriers. No association between the polymorphism and clinical parameters
      of tuberculosis severity was detected. However, our findings indicate that the
      rs1861494 single nucleotide polymorphism (SNP) could be considered as a biomarker
      of tuberculosis resistance in the Argentinean population.

PMID- 29361776
TI  - Mapping of Rice Varieties and Sowing Date Using X-Band SAR Data.
AB  - Rice is a major staple food for nearly half of the world's population and has a
      considerable contribution to the global agricultural economy. While spaceborne
      Synthetic Aperture Radar (SAR) data have proved to have great potential to
      provide rice cultivation area, few studies have been performed to provide
      practical information that meets the user requirements. In rice growing regions
      where the inter-field crop calendar is not uniform such as in the Mekong Delta in
      Vietnam, knowledge of the start of season on a field basis, along with the
      planted rice varieties, is very important for correct field management (timing of
      irrigation, fertilization, chemical treatment, harvest), and for market
      assessment of the rice production. The objective of this study is to develop
      methods using SAR data to retrieve in addition to the rice grown area, the sowing
      date, and the distinction between long and short cycle varieties. This study
      makes use of X-band SAR data from COSMO-SkyMed acquired from 19 August to 23
      November 2013 covering the Chau Thanh and Thoai Son districts in An Giang
      province, Viet Nam, characterized by a complex cropping pattern. The SAR data
      have been analyzed as a function of rice parameters, and the temporal and
      polarization behaviors of the radar backscatter of different rice varieties have
      been interpreted physically. New backscatter indicators for the detection of rice
      paddy area, the estimation of the sowing date, and the mapping of the short cycle
      and long cycle rice varieties have been developed and assessed. Good accuracy has
      been found with 92% in rice grown area, 96% on rice long or short cycle, and a
      root mean square error of 4.3 days in sowing date. The results have been
      discussed regarding the generality of the methods with respect to the rice
      cultural practices and the SAR data characteristics.

PMID- 29361777
TI  - Dual Channel S-Band Frequency Modulated Continuous Wave Through-Wall Radar
      Imaging.
AB  - This article deals with the development of a dual channel S-Band frequency
      modulated continuous wave (FMCW) system for a through-the-wall imaging (TWRI)
      system. Most existing TWRI systems using FMCW were developed for synthetic
      aperture radar (SAR) which has many drawbacks such as the need for several
      antenna elements and movement of the system. Our implemented TWRI system
      comprises a transmitting antenna and two receiving antennas, resulting in a
      significant reduction of the number of antenna elements. Moreover, a proposed
      algorithm for range-angle-Doppler 3D estimation based on a 3D shift invariant
      structure is utilized in our implemented dual channel S-band FMCW TWRI system.
      Indoor and outdoor experiments were conducted to image the scene beyond a wall
      for water targets and person targets, respectively. The experimental results
      demonstrate that high-quality imaging can be achieved under both experimental
      scenarios.

PMID- 29361778
TI  - Analysis of the Genetic Diversity and Population Structure of Austrian and
      Belgian Wheat Germplasm within a Regional Context Based on DArT Markers.
AB  - Analysis of crop genetic diversity and structure provides valuable information
      needed to broaden the narrow genetic base as well as to enhance the breeding and
      conservation strategies of crops. In this study, 95 Austrian and Belgian wheat
      cultivars maintained at the Centre for Genetic Resources (CGN) in the Netherlands
      were characterised using 1052 diversity array technology (DArT) markers to
      evaluate their genetic diversity, relationships and population structure. The
      rarefacted allelic richness recorded in the Austrian and Belgian breeding pools
      (A25 = 1.396 and 1.341, respectively) indicated that the Austrian germplasm
      contained a higher genetic diversity than the Belgian pool. The expected
      heterozygosity (HE) values of the Austrian and Belgian pools were 0.411 and
      0.375, respectively. Moreover, the values of the polymorphic information content
      (PIC) of the Austrian and Belgian pools were 0.337 and 0.298, respectively.
      Neighbour-joining tree divided each of the Austrian and Belgian germplasm pools
      into two genetically distinct groups. The structure analyses of the Austrian and
      Belgian pools were in a complete concordance with their neighbour-joining trees.
      Furthermore, the 95 cultivars were compared to 618 wheat genotypes from nine
      European countries based on a total of 141 common DArT markers in order to place
      the Austrian and Belgian wheat germplasm in a wider European context. The
      rarefacted allelic richness (A10) varied from 1.224 (Denmark) to 1.397 (Austria).
      Cluster and principal coordinates (PCoA) analyses divided the wheat genotypes of
      the nine European countries into two main clusters. The first cluster comprised
      the Northern and Western European wheat genotypes, whereas the second included
      the Central European cultivars. The structure analysis of the 618 European wheat
      genotypes was in a complete concordance with the results of cluster and PCoA
      analyses. Interestingly, a highly significant difference was recorded between
      regions (26.53%). In conclusion, this is the first study to reveal the high
      diversity levels and structure of the uncharacterised Austrian and Belgian wheat
      germplasm maintained at the CGN as well as place them in a wider European
      context. The results should help plant breeders to utilise the most promising
      wheat genotypes of this study in future breeding programmes for enhancing wheat
      cultivars.

PMID- 29361779
TI  - PGC1alpha: Friend or Foe in Cancer?
AB  - The PGC1 family (Peroxisome proliferator-activated receptor gamma (PPARgamma)
      coactivators) of transcriptional coactivators are considered master regulators of
      mitochondrial biogenesis and function. The PGC1alpha isoform is expressed
      especially in metabolically active tissues, such as the liver, kidneys and brain,
      and responds to energy-demanding situations. Given the altered and highly
      adaptable metabolism of tumor cells, it is of interest to investigate PGC1alpha
      in cancer. Both high and low levels of PGC1alpha expression have been reported to
      be associated with cancer and worse prognosis, and PGC1alpha has been attributed
      with oncogenic as well as tumor suppressive features. Early in carcinogenesis
      PGC1alpha may be downregulated due to a protective anticancer role, and low
      levels likely reflect a glycolytic phenotype. We suggest mechanisms of PGC1alpha
      downregulation and how these might be connected to the increased cancer risk that
      obesity is now known to entail. Later in tumor progression PGC1alpha is often
      upregulated and is reported to contribute to increased lipid and fatty acid
      metabolism and/or a tumor cell phenotype with an overall metabolic plasticity
      that likely supports drug resistance as well as metastasis. We conclude that in
      cancer PGC1alpha is neither friend nor foe, but rather the obedient servant
      reacting to metabolic and environmental cues to benefit the tumor cell.

PMID- 29361780
TI  - The Potential of Phytomelatonin as a Nutraceutical.
AB  - Phytomelatonin (plant melatonin) is chemically related to the amino acid
      tryptophan and has many diverse properties. Phytomelatonin is an interesting
      compound due to its outstanding actions at the cellular and physiological level,
      especially its protective effect in plants exposed to diverse stress situations,
      while its vegetable origin offers many opportunities because it is a natural
      compound. We present an overview of its origin, its action in plants in general
      (particularly in plant species with high levels of phytomelatonin), and its
      possibilities for use as a nutraceutical with particular attention paid to the
      beneficial effects that it may have in human health. The differences between
      synthetic melatonin and phytomelatonin, according to its origin and purity, are
      presented. Finally, the current market for phytomelatonin and its limits and
      potentials are discussed.

PMID- 29361781
TI  - An Inverse Neural Controller Based on the Applicability Domain of RBF Network
      Models.
AB  - This paper presents a novel methodology of generic nature for controlling
      nonlinear systems, using inverse radial basis function neural network models,
      which may combine diverse data originating from various sources. The algorithm
      starts by applying the particle swarm optimization-based non-symmetric variant of
      the fuzzy means (PSO-NSFM) algorithm so that an approximation of the inverse
      system dynamics is obtained. PSO-NSFM offers models of high accuracy combined
      with small network structures. Next, the applicability domain concept is suitably
      tailored and embedded into the proposed control structure in order to ensure that
      extrapolation is avoided in the controller predictions. Finally, an error
      correction term, estimating the error produced by the unmodeled dynamics and/or
      unmeasured external disturbances, is included to the control scheme to increase
      robustness. The resulting controller guarantees bounded input-bounded state
      (BIBS) stability for the closed loop system when the open loop system is BIBS
      stable. The proposed methodology is evaluated on two different control problems,
      namely, the control of an experimental armature-controlled direct current (DC)
      motor and the stabilization of a highly nonlinear simulated inverted pendulum.
      For each one of these problems, appropriate case studies are tested, in which a
      conventional neural controller employing inverse models and a PID controller are
      also applied. The results reveal the ability of the proposed control scheme to
      handle and manipulate diverse data through a data fusion approach and illustrate
      the superiority of the method in terms of faster and less oscillatory responses.

PMID- 29361782
TI  - Applications of Probe Capture Enrichment Next Generation Sequencing for Whole
      Mitochondrial Genome and 426 Nuclear SNPs for Forensically Challenging Samples.
AB  - The application of next generation sequencing (NGS) for the analysis of
      mitochondrial (mt) DNA, short tandem repeats (STRs), and single nucleotide
      polymorphism (SNPs) has demonstrated great promise for challenging forensic
      specimens, such as degraded, limited, and mixed samples. Target enrichment using
      probe capture rather than PCR amplification offers advantages for analysis of
      degraded DNA since two intact PCR primer sites in the template DNA molecule are
      not required. Furthermore, NGS software programs can help remove PCR duplicates
      to determine initial template copy numbers of a shotgun library. Moreover, the
      same shotgun library prepared from a limited DNA source can be enriched for mtDNA
      as well as nuclear markers by hybrid capture with the relevant probe panels.
      Here, we demonstrate the use of this strategy in the analysis of limited and mock
      degraded samples using our custom probe capture panels for massively parallel
      sequencing of the whole mtgenome and 426 SNP markers. We also applied the
      mtgenome capture panel in a mixed sample and analyzed using both phylogenetic and
      variant frequency based bioinformatics tools to resolve the minor and major
      contributors. Finally, the results obtained on individual telogen hairs
      demonstrate the potential of probe capture NGS analysis for both mtDNA and
      nuclear SNPs for challenging forensic specimens.

PMID- 29361783
TI  - Localization Microscopy Analyses of MRE11 Clusters in 3D-Conserved Cell Nuclei of
      Different Cell Lines.
AB  - In radiation biophysics, it is a subject of nowadays research to investigate DNA
      strand break repair in detail after damage induction by ionizing radiation. It is
      a subject of debate as to what makes up the cell's decision to use a certain
      repair pathway and how the repair machinery recruited in repair foci is spatially
      and temporarily organized. Single-molecule localization microscopy (SMLM) allows
      super-resolution analysis by precise localization of single fluorescent molecule
      tags, resulting in nuclear structure analysis with a spatial resolution in the 10
      nm regime. Here, we used SMLM to study MRE11 foci. MRE11 is one of three proteins
      involved in the MRN-complex (MRE11-RAD50-NBS1 complex), a prominent DNA strand
      resection and broken end bridging component involved in homologous recombination
      repair (HRR) and alternative non-homologous end joining (a-NHEJ). We analyzed the
      spatial arrangements of antibody-labelled MRE11 proteins in the nuclei of a
      breast cancer and a skin fibroblast cell line along a time-course of repair (up
      to 48 h) after irradiation with a dose of 2 Gy. Different kinetics for cluster
      formation and relaxation were determined. Changes in the internal nano-scaled
      structure of the clusters were quantified and compared between the two cell
      types. The results indicate a cell type-dependent DNA damage response concerning
      MRE11 recruitment and cluster formation. The MRE11 data were compared to H2AX
      phosphorylation detected by gammaH2AX molecule distribution. These data suggested
      modulations of MRE11 signal frequencies that were not directly correlated to DNA
      damage induction. The application of SMLM in radiation biophysics offers new
      possibilities to investigate spatial foci organization after DNA damaging and
      during subsequent repair.

PMID- 29361784
TI  - Identification of a Common Different Gene Expression Signature in Ischemic
      Cardiomyopathy.
AB  - The molecular mechanisms underlying the development of ischemic cardiomyopathy
      (ICM) remain poorly understood. Gene expression profiling is helpful to discover
      the molecular changes taking place in ICM. The aim of this study was to identify
      the genes that are significantly changed during the development of heart failure
      caused by ICM. The differentially expressed genes (DEGs) were identified from 162
      control samples and 227 ICM patients. PANTHER was used to perform gene ontology
      (GO), and Reactome for pathway enrichment analysis. A protein-protein interaction
      network was established using STRING and Cytoscape. A further validation was
      performed by real-time polymerase chain reaction (RT-PCR). A total of 255 common
      DEGs was found. Gene ontology, pathway enrichment, and protein-protein
      interaction analysis showed that nucleic acid-binding proteins, enzymes, and
      transcription factors accounted for a great part of the DEGs, while immune system
      signaling and cytokine signaling displayed the most significant changes.
      Furthermore, seven hub genes and nine transcription factors were identified.
      Interestingly, the top five upregulated DEGs were located on chromosome Y, and
      four of the top five downregulated DEGs were involved in immune and inflammation
      signaling. Further, the top DEGs were validated by RT-PCR in human samples. Our
      study explored the possible molecular mechanisms of heart failure caused by
      ischemic heart disease.

PMID- 29361785
TI  - MHC-Dependent Mate Selection within 872 Spousal Pairs of European Ancestry from
      the Health and Retirement Study.
AB  - Disassortative mating refers to the phenomenon in which individuals with
      dissimilar genotypes and/or phenotypes mate with one another more frequently than
      would be expected by chance. Although the existence of disassortative mating is
      well established in plant and animal species, the only documented example of
      negative assortment in humans involves dissimilarity at the major
      histocompatibility complex (MHC) locus. Previous studies investigating mating
      patterns at the MHC have been hampered by limited sample size and contradictory
      findings. Inspired by the sparse and conflicting evidence, we investigated the
      role that the MHC region played in human mate selection using genome-wide
      association data from 872 European American spouses from the Health and
      Retirement Study (HRS). First, we treated the MHC region as a whole, and
      investigated genomic similarity between spouses using three levels of genomic
      variation: single-nucleotide polymorphisms (SNPs), classical human leukocyte
      antigen (HLA) alleles (both four-digit and two-digit classifications), and amino
      acid polymorphisms. The extent of MHC dissimilarity between spouses was assessed
      using a permutation approach. Second, we investigated fine scale mating patterns
      by testing for deviations from random mating at individual SNPs, HLA genes, and
      amino acids in HLA molecules. Third, we assessed how extreme the spousal
      relatedness at the MHC region was compared to the rest of the genome, to
      distinguish the MHC-specific effects from genome-wide effects. We show that
      neither the MHC region, nor any single SNPs, classic HLA alleles, or amino acid
      polymorphisms within the MHC region, were significantly dissimilar between
      spouses relative to non-spouse pairs. However, dissimilarity in the MHC region
      was extreme relative to the rest of genome for both spousal and non-spouse pairs.
      Despite the long-standing controversy, our analyses did not support a significant
      role of MHC dissimilarity in human mate choice.

PMID- 29361786
TI  - Speaking Up: Veterinary Ethical Responsibilities and Animal Welfare Issues in
      Everyday Practice.
AB  - Although expectations for appropriate animal care are present in most developed
      countries, significant animal welfare challenges continue to be seen on a regular
      basis in all areas of veterinary practice. Veterinary ethics is a relatively new
      area of educational focus but is thought to be critically important in helping
      veterinarians formulate their approach to clinical case management and in
      determining the overall acceptability of practices towards animals. An overview
      is provided of how veterinary ethics are taught and how common ethical frameworks
      and approaches are employed-along with legislation, guidelines and codes of
      professional conduct-to address animal welfare issues. Insufficiently mature
      ethical reasoning or a lack of veterinary ethical sensitivity can lead to an
      inability or difficulty in speaking up about concerns with clients and
      ultimately, failure in their duty of care to animals, leading to poor animal
      welfare outcomes. A number of examples are provided to illustrate this point.
      Ensuring that robust ethical frameworks are employed will ultimately help
      veterinarians to "speak up" to address animal welfare concerns and prevent future
      harms.

PMID- 29361787
TI  - Differential Gene Expression in Response to Salinity and Temperature in a
      Haloarcula Strain from Great Salt Lake, Utah.
AB  - Haloarchaea that inhabit Great Salt Lake (GSL), a thalassohaline terminal lake,
      must respond to the fluctuating climate conditions of the elevated desert of
      Utah. We investigated how shifting environmental factors, specifically salinity
      and temperature, affected gene expression in the GSL haloarchaea, NA6-27, which
      we isolated from the hypersaline north arm of the lake. Combined data from
      cultivation, microscopy, lipid analysis, antibiotic sensitivity, and 16S rRNA
      gene alignment, suggest that NA6-27 is a member of the Haloarcula genus. Our
      prior study demonstrated that archaea in the Haloarcula genus were stable in the
      GSL microbial community over seasons and years. In this study, RNA arbitrarily
      primed PCR (RAP-PCR) was used to determine the transcriptional responses of NA6
      27 grown under suboptimal salinity and temperature conditions. We observed
      alteration of the expression of genes related to general stress responses, such
      as transcription, translation, replication, signal transduction, and energy
      metabolism. Of the ten genes that were expressed differentially under stress,
      eight of these genes responded in both conditions, highlighting this general
      response. We also noted gene regulation specific to salinity and temperature
      conditions, such as osmoregulation and transport. Taken together, these data
      indicate that the GSL Haloarcula strain, NA6-27, demonstrates both general and
      specific responses to salinity and/or temperature stress, and suggest a
      mechanistic model for homeostasis that may explain the stable presence of this
      genus in the community as environmental conditions shift.

PMID- 29361788
TI  - MiR-93-5p Promotes Cell Proliferation through Down-Regulating PPARGC1A in
      Hepatocellular Carcinoma Cells by Bioinformatics Analysis and Experimental
      Verification.
AB  - Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A,
      formerly known as PGC-1a) is a transcriptional coactivator and metabolic
      regulator. Previous studies are mainly focused on the association between
      PPARGC1A and hepatoma. However, the regulatory mechanism remains unknown. A
      microRNA associated with cancer (oncomiR), miR-93-5p, has recently been found to
      play an essential role in tumorigenesis and progression of various carcinomas,
      including liver cancer. Therefore, this paper aims to explore the regulatory
      mechanism underlying these two proteins in hepatoma cells. Firstly, an
      integrative analysis was performed with miRNA-mRNA modules on microarray and The
      Cancer Genome Atlas (TCGA) data and obtained the core regulatory network and miR
      93-5p/PPARGC1A pair. Then, a series of experiments were conducted in hepatoma
      cells with the results including miR-93-5p upregulated and promoted cell
      proliferation. Thirdly, the inverse correlation between miR-93-5p and PPARGC1A
      expression was validated. Finally, we inferred that miR-93-5p plays an essential
      role in inhibiting PPARGC1A expression by directly targeting the 3'-untranslated
      region (UTR) of its mRNA. In conclusion, these results suggested that miR-93-5p
      overexpression contributes to hepatoma development by inhibiting PPARGC1A. It is
      anticipated to be a promising therapeutic strategy for patients with liver cancer
      in the future.

PMID- 29361789
TI  - Anti-Inflammatory Effects of a Stauntonia hexaphylla Fruit Extract in
      Lipopolysaccharide-Activated RAW-264.7 Macrophages and Rats by Carrageenan
      Induced Hind Paw Swelling.
AB  - The fruit of Stauntoniahexaphylla is commonly used as a traditional anthelmintic
      in Korea, Japan, and China. However, its anti-inflammatory activity and the
      underlying mechanisms have not been studied systematically. In the present study,
      we examined the anti-inflammatory activities of an aqueous extract of S.
      hexaphylla fruit (SHF) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. The
      SHF extract contained anti-inflammatory compounds, such as neochlorogenic acid,
      chlorogenic acid, and cryptochlorogenic acid. The extract inhibited protein
      levels of inducible nitric oxide synthase and the activity of cyclooxygenase
      enzyme, with concomitant reductions in the production of nitric oxide and
      prostaglandin E2 in LPS-activated RAW 264.7 cells. Additionally, the SHF extract
      reduced the production of pro-inflammatory cytokines, including tumor necrosis
      factor-alpha, interleukin (IL)-1beta, and IL-6. The SHF extract attenuated LPS
      induced nuclear factor-kappaB (NF-kappaB) activation by decreasing the
      phosphorylation of its inhibitor, IkappaBalpha. Furthermore, the SHF extract
      showed a significant anti-inflammatory effect in vivo by reducing the volume of
      carrageenan-induced paw edema in rats. Our results suggest that the SHF extract
      exerts potential anti-inflammatory properties against LPS-activated RAW 254.7
      cells, and in an animal model of inflammation.

PMID- 29361791
TI  - Groundwater Pollution Sources Apportionment in the Ghaen Plain, Iran.
AB  - Although Iran's Ghaen Plain provides saffron to much of the world, no regional
      groundwater quality (GQ) assessment has yet been undertaken. Given the region's
      potential for saltwater intrusion and heavy metal contamination, it is important
      to assess the GQ and determine its main probable source of pollution (MPSP). Such
      knowledge would allow for informed mitigation or elimination of the potential
      adverse health effects of this groundwater through its use as drinking water, or
      indirectly as a result of the consumption of groundwater-irrigated crops. Total
      dissolved solids, sodium, and chloride in the water of the majority of 16 wells
      sampled within the region exceeded World Health Organization and Iranian
      permissible standards for drinking water. The groundwater proved to only be
      suitable for irrigating salt tolerant crops under good drainage conditions. Due
      to the precipitation of calcium carbonate in the water supply facilities, the
      water from all wells was deemed unsuitable for industrial purposes. Heavy metal
      pollution and contamination indices showed no groundwater contamination. Analysis
      of ionic ratios and the application of principal components analysis indicated
      the MPSP to be saltwater intrusion, with the geology subtending the plain, and to
      a lesser extent, anthropogenic activities. Reducing groundwater withdrawals,
      particularly those for agricultural production by using high performance
      irrigation methods could reduce saltwater intrusion and improve GQ in the Ghaen
      Plain.

PMID- 29361790
TI  - Single-Cell Genomic Analysis in Plants.
AB  - Individual cells in an organism are variable, which strongly impacts cellular
      processes. Advances in sequencing technologies have enabled single-cell genomic
      analysis to become widespread, addressing shortcomings of analyses conducted on
      populations of bulk cells. While the field of single-cell plant genomics is in
      its infancy, there is great potential to gain insights into cell lineage and
      functional cell types to help understand complex cellular interactions in plants.
      In this review, we discuss current approaches for single-cell plant genomic
      analysis, with a focus on single-cell isolation, DNA amplification, next
      generation sequencing, and bioinformatics analysis. We outline the technical
      challenges of analysing material from a single plant cell, and then examine
      applications of single-cell genomics and the integration of this approach with
      genome editing. Finally, we indicate future directions we expect in the rapidly
      developing field of plant single-cell genomic analysis.

PMID- 29361792
TI  - Number of Heat Wave Deaths by Diagnosis, Sex, Age Groups, and Area, in Slovenia,
      2015 vs. 2003.
AB  - Background: Number of deaths increases during periods of elevated heat.
      Objectives: To examine whether differences in heat-related deaths between 2003
      and 2015 occurred in Slovenia. Materials and Methods: We estimated relative risks
      for deaths for the observed diagnoses, sex, age, and area, as well as 95%
      confidence intervals and excess deaths associated with heat waves occurring in
      2015 and 2003. For comparison between 2015 and 2003, we calculated relative risks
      ratio and 95% confidence intervals. Results: Statistically significant in 2015
      were the following: age group 75+, all causes of deaths (RR = 1.10, 95% CI 1.00
      1.22); all population, circulatory system diseases (RR = 1.14, 95% CI 1.01-1.30)
      and age group 75+, diseases of circulatory system (RR = 1.17, 95% CI 1.01-1.34).
      Statistically significant in 2003 were the following: female, age group 5-74,
      circulatory system diseases (RR = 1.69, 95% CI 1.08-2.62). Discussion: Comparison
      between 2015 and 2003, all, circulatory system diseases (RRR = 1.25, 95% CI 1.01
      1.55); male, circulatory system diseases (RRR = 1.85, 95% CI 1.41-2.43); all, age
      group 75+ circulatory system diseases (RRR = 1.34, 95% CI 1.07-1.69); male, age
      group 75+, circulatory system diseases (RRR = 1.52, 95% CI 1.03-2.25) and female,
      age group 75+, circulatory system diseases (RRR = 1.43, 95% CI 1.08-1.89).
      Conclusions: Public health efforts are urgent and should address circulatory
      system causes and old age groups.

PMID- 29361794
TI  - Arsenic Methylation Capacity and Metabolic Syndrome in the 2013-2014 U.S.
      National Health and Nutrition Examination Survey (NHANES).
AB  - Arsenic methylation capacity is associated with metabolic syndrome and its
      components among highly exposed populations. However, this association has not
      been investigated in low to moderately exposed populations. Therefore, we
      investigated arsenic methylation capacity in relation to the clinical diagnosis
      of metabolic syndrome in a low arsenic exposure population. Additionally, we
      compared arsenic methylation patterns present in our sample to those of more
      highly exposed populations. Using logistic regression models adjusted for
      relevant biological and lifestyle covariates, we report no association between
      increased arsenic methylation and metabolic syndrome in a population in which
      arsenic is regulated at 10 ppb in drinking water. However, we cannot rule out the
      possibility of a positive association between arsenic methylation and metabolic
      syndrome in a subsample of women with normal body mass index (BMI). To our
      knowledge this is the first investigation of arsenic methylation capacity with
      respect to metabolic syndrome in a low exposure population. We also report that
      methylation patterns in our sample are similar to those found in highly exposed
      populations. Additionally, we report that gender and BMI significantly modify the
      effect of arsenic methylation on metabolic syndrome. Future studies should
      evaluate the effectiveness of arsenic policy enforcement on subclinical
      biomarkers of cardiovascular disease.

PMID- 29361793
TI  - The Association of Food Consumption Scores, Body Shape Index, and Hypertension in
      a Seven-Year Follow-Up among Indonesian Adults: A Longitudinal Study.
AB  - Aims: The concept of food security and its association with chronic diseases are
      both well-established. During the years within the scope of the study, there was
      a significant increase in the body shape index (ABSI) of Indonesian adults. This
      study tested the hypothesis that the association between food security and
      chronic diseases is mediated, in part, by ABSI. Methods: Data was obtained from
      2156 Indonesian adults using the Indonesia Family Life Survey (IFLS) in 2007 and
      2014. Longitudinal study participants were interviewed face-to-face for dietary
      intake data using the food frequency questionnaire (FFQ). Food security, a
      concept developed by the World Food Programme (WFP), was calculated based on a
      food consumption score analysis using the FFQ. A generalized estimating equation
      (GEE) and a Sobel-Goodman test were used to test the hypothesis in this study.
      Results: The food consumption score was negatively associated with ABSI. It was
      also negatively associated with systolic blood pressure (p < 0.001). In a formal
      mediation analysis, ABSI significantly mediated the pathway between the food
      consumption score and systolic blood pressure (p < 0.001). Conclusions: The
      effect of food security on hypertension is mediated through body shape.
      Strategies to improve the prevention of hypertension among adults may need to
      take the ABSI and food security, along with nutrition education, into account.

PMID- 29361795
TI  - A Comparative Pharmacokinetic Study by UHPLC-MS/MS of Main Active Compounds after
      Oral Administration of Zushima-Gancao Extract in Normal and Adjuvant-Induced
      Arthritis Rats.
AB  - A sensitive and rapid ultra high-performance liquid-chromatography tandem mass
      spectrometry (UHPLC-MS/MS) method has been applied to investigate the influence
      of rheumatoid arthritis (RA) on the pharmacokinetics of nine analytes (daphnetin,
      daphnoretin, 7-hydroxycoumarin, liquiritin, isoliquiritin, liquiritigenin,
      isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid), which are major active
      components in Zushima-Gancao extract. The analytes and internal standard (IS)
      were separated in a Hypersil Gold C18 column and detected on a triple-stage
      quadrupole mass spectrometer using the validated method. All analytes exhibited
      good linearities (R2 > 0.98), and the lower limit of quantification (LLOQs) were
      sufficient for quantitative analysis. Intra- and inter-batch precision were all
      within 14.96% while the accuracy of nine analytes ranged from -17.99 to 14.48%,
      and these results were all within acceptance criteria. The extraction recoveries,
      matrix effects, and stabilities were all satisfactory. Main pharmacokinetic
      parameters of each compound were compared, and significant differences were found
      in parameters of daphnetin, daphnoretin, liquiritin, isoliquiritin,
      isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid, especially the last
      one, between the two groups. Therefore, adjuvant-induced arthritis has different
      effects on the pharmacokinetics of ingredients in Zushima-Gancao extract. The
      comparative pharmacokinetic study between normal and adjuvant-induced arthritis
      rats might provide more comprehensive information to guide the clinical usage of
      Zushima-Gancao extract for treating RA.

PMID- 29361796
TI  - Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of
      Pregnancy.
AB  - Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother
      and the unborn offspring, develops in the last trimester of pregnancy with
      significant maternal and perinatal mortality. AFLP is also recognized as an
      obstetric and medical emergency. Maternal AFLP is highly associated with a fetal
      homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long
      chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in
      the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3
      hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are
      then shunted to the maternal circulation leading to the development of acute
      liver injury observed in patients with AFLP. In this review, we will discuss the
      mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the
      liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte
      lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in
      causing placental damage, pancreatic islet beta-cell glucolipotoxicity, brain
      damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD
      deficiency.

PMID- 29361798
TI  - Orientation of Steel Fibers in Magnetically Driven Concrete and Mortar.
AB  - The orientation of steel fibers in magnetically driven concrete and magnetically
      driven mortar was experimentally studied in this paper using a magnetic method.
      In the magnetically driven concrete, a steel slag was used to replace the coarse
      aggregate. In the magnetically driven mortar, steel slag and iron sand were used
      to replace the fine aggregate. A device was established to provide the magnetic
      force. The magnetic force was used to rotate the steel fibers. In addition, the
      magnetic force was also used to vibrate the concrete and mortar. The effect of
      magnetic force on the orientation of steel fibers was examined by comparing the
      direction of fibers before and after vibration. The effect of magnetically driven
      concrete and mortar on the orientation of steel fibers was also examined by
      comparing specimens to normal concrete and mortar. It is shown that the fibers
      could rotate about 90 degrees  in magnetically driven concrete. It is also shown
      that the number of fibers rotated in magnetically driven mortar was much more
      than in mortar vibrated using a shaking table. A splitting test was performed on
      concrete specimens to investigate the effect of fiber orientation. In addition, a
      flexural test was also performed on mortar test specimens. It is shown that the
      orientation of the steel fibers in magnetically driven concrete and mortar
      affects the strength of the concrete and mortar specimens.

PMID- 29361797
TI  - Biochemical Analysis of the Role of Leucine-Rich Repeat Receptor-Like Kinases and
      the Carboxy-Terminus of Receptor Kinases in Regulating Kinase Activity in
      Arabidopsis thaliana and Brassica oleracea.
AB  - Protein post-translational modification by phosphorylation is essential for the
      activity and stability of proteins in higher plants and underlies their responses
      to diverse stimuli. There are more than 300 leucine-rich repeat receptor-like
      kinases (LRR-RLKs), a major group of receptor-like kinases (RLKs) that plays an
      important role in growth, development, and biotic stress responses in higher
      plants. To analyze auto- and transphosphorylation patterns and kinase activities
      in vitro, 43 full-length complementary DNA (cDNA) sequences were cloned from
      genes encoding LRR-RLKs. Autophosphorylation activity was found in the
      cytoplasmic domains (CDs) of 18 LRR-RLKs; 13 of these LRR-RLKs with
      autophosphorylation activity showed transphosphorylation in Escherichiacoli. BRI1
      Associated Receptor Kinase (BAK1), which is critically involved in the
      brassinosteroid and plant innate immunity signal transduction pathways, showed
      strong auto- and transphosphorylation with multi-specific kinase activity within
      2 h of induction of Brassica oleraceae BAK1-CD (BoBAK1-CD) in E. coli; moreover,
      the carboxy-terminus of LRR-RLKs regulated phosphorylation and kinase activity in
      Arabidopsis thaliana and vegetative crops.

PMID- 29361799
TI  - Preparedness of Health Care Professionals for Delivering Sexual and Reproductive
      Health Care to Refugee and Migrant Women: A Mixed Methods Study.
AB  - Past research suggests that factors related to health care professionals' (HCPs)
      knowledge, training and competency can contribute to the underutilisation of
      sexual and reproductive health (SRH) care by refugee and migrant women. The aim
      of this study was to examine the perceived preparedness of HCPs in relation to
      their knowledge, confidence and training needs when it comes to consulting
      refugee and migrant women seeking SRH care in Australia. A sequential mixed
      methods design, comprising an online survey with 79 HCPs (45.6% nurses, 30.3%
      general practitioners (GPs), 16.5% health promotion officers, and 7.6% allied
      health professionals) and semi-structured interviews with 21 HCPs, was utilised.
      HCPs recognised refugee and migrant women's SRH as a complex issue that requires
      unique skills for the delivery of optimal care. However, they reported a lack of
      training (59.4% of nurses, 50% of GPs, and 38.6% of health promotion officers)
      and knowledge (27.8% of nurses, 20.8% of GPs, and 30.8% of health promotion
      officers) in addressing refugee and migrant women's SRH. The majority of
      participants (88.9% of nurses, 75% of GPs, and 76% of health promotion officers)
      demonstrated willingness to engage with further training in refugee and migrant
      women's SRH. The implications of the findings are argued regarding the need to
      train HCPs in culturally sensitive care and include the SRH of refugee and
      migrant women in university and professional development curricula in meeting the
      needs of this growing and vulnerable group of women.

PMID- 29361801
TI  - Genome-Wide Identification and Characterization of the Potato bHLH Transcription
      Factor Family.
AB  - Plant basic/helix-loop-helix (bHLH) transcription factors participate in a number
      of biological processes, such as growth, development and abiotic stress
      responses. The bHLH family has been identified in many plants, and several bHLH
      transcription factors have been functionally characterized in Arabidopsis.
      However, no systematic identification of bHLH family members has been reported in
      potato (Solanum tuberosum). Here, 124 StbHLH genes were identified and named
      according to their chromosomal locations. The intron numbers varied from zero to
      seven. Most StbHLH proteins had the highly conserved intron phase 0, which
      accounted for 86.2% of the introns. According to the Neighbor-joining
      phylogenetic tree, 259 bHLH proteins acquired from Arabidopsis and potato were
      divided into 15 groups. All of the StbHLH genes were randomly distributed on 12
      chromosomes, and 20 tandem duplicated genes and four pairs of duplicated gene
      segments were detected in the StbHLH family. The gene ontology (GO) analysis
      revealed that StbHLH mainly function in protein and DNA binding. Through the RNA
      seq and quantitative real time PCR (qRT-PCR) analyses, StbHLH were found to be
      expressed in various tissues and to respond to abiotic stresses, including salt,
      drought and heat. StbHLH1, 41 and 60 were highly expressed in flower tissues, and
      were predicted to be involved in flower development by GO annotation. StbHLH45
      was highly expressed in salt, drought and heat stress, which suggested its
      important role in abiotic stress response. The results provide comprehensive
      information for further analyses of the molecular functions of the StbHLH gene
      family.

PMID- 29361802
TI  - Metagenomics of Bacterial Diversity in Villa Luz Caves with Sulfur Water Springs.
AB  - New biotechnology applications require in-depth preliminary studies of
      biodiversity. The methods of massive sequencing using metagenomics and
      bioinformatics tools offer us sufficient and reliable knowledge to understand
      environmental diversity, to know new microorganisms, and to take advantage of
      their functional genes. Villa Luz caves, in the southern Mexican state of
      Tabasco, are fed by at least 26 groundwater inlets, containing 300-500 mg L-1 H2S
      and <0.1 mg L-1 O2. We extracted environmental DNA for metagenomic analysis of
      collected samples in five selected Villa Luz caves sites, with pH values from 2.5
      to 7. Foreign organisms found in this underground ecosystem can oxidize H2S to
      H2SO4. These include: biovermiculites, a bacterial association that can grow on
      the rock walls; snottites, that are whitish, viscous biofilms hanging from the
      rock walls, and sacks or bags of phlegm, which live within the aquatic
      environment of the springs. Through the emergency food assistance program (TEFAP)
      pyrosequencing, a total of 20,901 readings of amplification products from
      hypervariable regions V1 and V3 of 16S rRNA bacterial gene in whole and pure
      metagenomic DNA samples were generated. Seven bacterial phyla were identified. As
      a result, Proteobacteria was more frequent than Acidobacteria. Finally,
      acidophilic Proteobacteria was detected in UJAT5 sample.

PMID- 29361803
TI  - Overall Survival of Ovarian Cancer Patients Is Determined by Expression of
      Galectins-8 and -9.
AB  - The evaluation of new prognostic factors that can be targeted in ovarian cancer
      diagnosis and therapy is of the utmost importance. Galectins are a family of
      carbohydrate binding proteins with various implications in cancer biology. In
      this study, the presence of galectin (Gal)-8 and -9 was investigated in 156
      ovarian cancer samples using immunohistochemistry (IHC). Staining was evaluated
      using semi-quantitative immunoreactivity (IR) scores and correlated to clinical
      and pathological data. Different types of galectin expression were compared with
      respect to disease-free survival (DFS) and overall survival (OS). Gal-8 served as
      a new positive prognostic factor for the OS and DFS of ovarian cancer patients.
      Gal-9 expression determined the DFS and OS of ovarian cancer patients in two
      opposing ways-moderate Gal-9 expression was correlated with a reduced outcome as
      compared to Gal-9 negative cases, while patients with high Gal-9 expression
      showed the best outcome.

PMID- 29361805
TI  - EKF-GPR-Based Fingerprint Renovation for Subset-Based Indoor Localization with
      Adjusted Cosine Similarity.
AB  - Received Signal Strength Indicator (RSSI) localization using fingerprint has
      become a prevailing approach for indoor localization. However, the fingerprint
      collecting work is repetitive and time-consuming. After the original fingerprint
      radio map is built, it is laborious to upgrade the radio map. In this paper, we
      describe a Fingerprint Renovation System (FRS) based on crowdsourcing, which
      avoids the use of manual labour to obtain the up-to-date fingerprint status.
      Extended Kalman Filter (EKF) and Gaussian Process Regression (GPR) in FRS are
      combined to calculate the current state based on the original fingerprinting
      radio map. In this system, a method of subset acquisition also makes an immediate
      impression to reduce the huge computation caused by too many reference points
      (RPs). Meanwhile, adjusted cosine similarity (ACS) is employed in the online
      phase to solve the issue of outliers produced by cosine similarity. Both
      experiments and analytical simulation in a real Wireless Fidelity (Wi-Fi)
      environment indicate the usefulness of our system to significant performance
      improvements. The results show that FRS improves the accuracy by 19.6% in the
      surveyed area compared to the radio map un-renovated. Moreover, the proposed
      subset algorithm can bring less computation.

PMID- 29361807
TI  - [Quality is the Key for Emerging Issues of Population-based Colonoscopy
      Screening].
AB  - Colonoscopy is currently regarded as the gold standard and preferred method of
      screening for colorectal cancer (CRC). However, the benefit of colonoscopy
      screening may be blunted by low participation rate in population-based screening
      program. Harmful effects of population-based colonoscopy screening may include
      complications induced by colonoscopy itself and by sedation, psychosocial
      distress, potential over-diagnosis and socioeconomic burden. In addition, harmful
      effect of colonoscopy may increase with age and comorbidity. As the adverse event
      risk in population-based colonoscopy screening may offset benefit of the
      screening colonoscopy, the adverse events associated with screening colonoscopy
      should be well managed and monitored. To adopt population-based colonoscopy
      screening, consensus for the risk and benefits of screening colonoscopy should be
      formed for its potential harms, patient preference, socioeconomic considerations,
      quality improvement of colonoscopy as well as its efficacy for CRC prevention. As
      the suboptimal colonoscopy quality is a major pitfall of population-based
      colonoscopy screening, adequate training and provider regulation for screening
      colonoscopists should be the first step to minimize the variation of quality
      between colonoscopists. Gastroenterologists should lead quality improvement,
      auditing, and training associated with colonoscopy in a population-based
      colonoscopy screening program.

PMID- 29361800
TI  - Heat Shock Proteins and Autophagy Pathways in Neuroprotection: from Molecular
      Bases to Pharmacological Interventions.
AB  - Neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's
      disease and Huntington's disease (HD), amyotrophic lateral sclerosis, and prion
      diseases are all characterized by the accumulation of protein aggregates
      (amyloids) into inclusions and/or plaques. The ubiquitous presence of amyloids in
      NDDs suggests the involvement of disturbed protein homeostasis (proteostasis) in
      the underlying pathomechanisms. This review summarizes specific mechanisms that
      maintain proteostasis, including molecular chaperons, the ubiquitin-proteasome
      system (UPS), endoplasmic reticulum associated degradation (ERAD), and different
      autophagic pathways (chaperon mediated-, micro-, and macro-autophagy). The role
      of heat shock proteins (Hsps) in cellular quality control and degradation of
      pathogenic proteins is reviewed. Finally, putative therapeutic strategies for
      efficient removal of cytotoxic proteins from neurons and design of new
      therapeutic targets against the progression of NDDs are discussed.

PMID- 29361808
TI  - [Endoscopic Treatment for Pancreatic Cystic Lesions].
AB  - The decision of the appropriate treatment for pancreatic cystic lesions (PCLs) is
      becoming increasingly important as the number of incidentally found PCLs
      increases. A range of modalities have been attempted because there has been an
      increasing demand for minimally invasive treatment for PCLs due to the large
      burden of a surgical resection. Endoscopic treatment using endoscopic
      ultrasonography (EUS), a representative of minimally invasive therapy, can be
      categorized into two types: ablation therapy by the injection of drugs and
      topical thermal coagulative therapy through the high topical energy. A number of
      studies reported the feasibility and efficacy of these treatments; the most
      common is EUS-guided ablation for PCLS with ethanol alone or in combination with
      anticancer drugs. Although ablation therapies with drug injection have proven
      safety and feasibility, there is no consensus regarding the actual treatment
      effects and indications of these modalities. EUS-guided radiofrequency ablation
      was recently attempted as a representative method of local thermal coagulation,
      but further studies will be needed because of the lack of evidence of its
      feasibility and safety. In addition, a range of treatments for malignant tumors
      rather than PCLs have been attempted, such as EUS-guided photodynamic therapy,
      EUS-guided neodymium-doped yttrium aluminum garnet laser, and high-intensity
      focused ultrasound, based on the data from animal experiments. Through further
      study, endoscopic treatment is expected to become established as a useful
      treatment modality for PCLs.

PMID- 29361804
TI  - Global Mortality Burden of Cirrhosis and Liver Cancer Attributable to Injection
      Drug Use, 1990-2016: An Age-Period-Cohort and Spatial Autocorrelation Analysis.
AB  - We analyzed the temporal and spatial variations in mortality burden of cirrhosis
      and liver cancer attributable to injection drug use (IDU) from 1990 to 2016.
      Mortality data of IDU-attributable cirrhosis and IDU-attributable liver cancer on
      the global and national scales from 1990 to 2016 were collected from the Global
      Burden of Disease (GBD) studies. Age-period-cohort (APC) model analysis was used
      to analyze the global mortality trends of target disease, and spatial
      autocorrelation analysis based on Geographic Information System was applied to
      illustrate the clusters of the most epidemic countries. Globally, from 1990 to
      2015, mortality rates (age-standardized, per 100,000) of IDU-attributable
      cirrhosis increased continually from 1.5 to 1.9, while from 0.4 to 0.9 for IDU
      attributable liver cancer. The APC model analysis indicated that the increases of
      mortality were mainly driven by period effects, with the mortality risk
      increasing by 6.82-fold for IDU-attributable cirrhosis and 3.08-fold for IDU
      attributable liver cancer. The spatial analysis suggested that IDU-attributable
      cirrhosis mortality were geographically clustered from 1990 to 2016, and hot
      spots were mainly located in less well developed countries of Latin America, East
      and Central Europe and Central Asia. Our study provides epidemiological evidence
      for global interventions against advanced liver disease among injection drug
      users (IDUs).

PMID- 29361806
TI  - Molecular Identification of Eimeria Species in Broiler Chickens in Trinidad, West
      Indies.
AB  - Coccidiosis is an intestinal disease of chickens of major economic importance to
      broiler industries worldwide. Species of coccidia found in chickens include
      Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria mitis, Eimeria
      necatrix, Eimeria praecox, and Eimeria tenella. In recent years, polymerase chain
      reaction (PCR) has been developed to provide accurate and rapid identification of
      the seven known Eimeria species of chickens. The aim of this study was to use
      species-specific real-time PCR (qPCR) to identify which of the seven Eimeria
      species are present in Trinidad poultry. Seventeen pooled fecal samples were
      collected from 6 broiler farms (2-5 pens per farm) across Trinidad. Feces were
      also collected from birds showing clinical signs of coccidiosis in two live bird
      markets (pluck shops). qPCR revealed the presence of five species of Eimeria (E.
      acervulina, E. maxima, E. mitis, E. necatrix, and E. tenella), but not E.
      brunetti or E. praecox. Mixed infections were detected on all broiler farms, and
      DNA of two highly pathogenic Eimeria species (E. tenella and E.necatrix) was
      detected in feces taken from clinically sick birds sampled from the two pluck
      shops.

PMID- 29361809
TI  - [The Prevalence of Nontuberculous Mycobacterial Lung Disease with orwithout
      Reflux Esophagitis].
AB  - Background/Aims: Gastrointestinal reflux disease (GERD) is defined as 'a
      condition that develops when the reflux of stomach contents causes troublesome
      symptoms and/or complications'. It is associated with various lung diseases,
      including bronchial asthma, chronic bronchitis, and bronchiectasis. GERD may also
      affect nontuberculous mycobacterial (NTM) lung disease. We presumed that the
      normal mucosal barrier of the bronchial epithelium is broken due to the
      aspiration of gastric juice and consequent chronic bronchial inflammation. This
      study investigated the prevalence of GERD in accordance with the presence or
      absence of NTM lung disease and analyzed the difference. Methods: We screened
      patients with NTM lung disease in this hospital between January 2011 and December
      2015. Among these patients, gastroscopic examinations as a health check-up were
      performed on 93 patients. We obtained the prevalence of Reflux esophagitis (RE)
      in patients with NTM and compared it with the prevalence of RE in the normal
      control subjects. Results: Among 93 patients with NTM, patients without RE was
      66.7% (62/93). RE-minimal change was diagnosed in 29.0% (27/93), and RE LA-A was
      diagnosed in 4.3% (4/93). Comparing the prevalence of RE minimal change, 29.0%
      (27/93) had NTM and 11.9% (3043/25536) did not have NTM. This was statistically
      significant. Conclusions: We showed a greater prevalence of RE minimal change in
      patients with NTM than those without NTM with statistical significance.

PMID- 29361810
TI  - [Clinical Course of Percutaneous Endoscopic Gastrostomy: A Single-center
      Observational Study].
AB  - Background/Aims: Percutaneous endoscopic gastrostomy (PEG) is a widely used
      method for long-term tube feeding. This study aimed to investigate the clinical
      characteristics and outcomes of patients who utilized long-term feeding tube via
      PEG. Methods: The medical records of 137 patients who underwent PEG tube
      insertion at Ewha Womans University Mokdong Hospital between January 2002 and
      December 2013 were reviewed. Results: PEG was indicated most frequently for
      cerebrovascular accidents (66 patients, 48.2%), followed by head and neck cancer
      (20 patients, 14.6%), and Parkinson's disease (10 patients, 7.3%). The tubes were
      endoscopically inserted in 133 patients (97.1%); 4 patients (2.9%) underwent
      radiologic intervention. The tubes of 90 patients (65.7%) were exchanged at least
      once during the follow- up period. At the first exchange, 71 patients (78.9%) had
      their tubes exchanged by endoscopy, 24 patients (16.7%) by manually, and 4
      patients (4.4%) by radiologic intervention. Of the 61 patients (44.5%) who had
      their tubes exchanged twice, 44 patients (72.1%) changed their tubes by
      endoscopic exchange, 13 patients (21.3%) by manually, and 4 patients (4.4%) via
      radiologic intervention. The mean time interval between the initial insertion and
      the first exchange was 9.83+/-6.19 months, and that between the initial insertion
      and the second exchange was 10.7+/-6.25 months. Of all the 137 patients, acute
      complications at initial insertion occurred in only 18 patients (13.1%), with
      insertion site infection (9 patients, 6.6%) being the most common acute
      complication. Conclusions: PEG appears to be a safe procedure for providing long
      term tube feeding. Our results may help to develop strategies for further
      management of subjects receiving feeding tubes via PEG.

PMID- 29361811
TI  - Concomitant or Sequential Therapy as the First-line Therapy for Eradication of
      Helicobacter pylori Infection in Korea: A Systematic Review and Meta-analysis.
AB  - Background/Aims: In Korea, increasing clarithromycin resistance has led to the
      need for an alternative first-line therapy for the eradication of Helicobacter
      pylori (H. pylori) infection. Concomitant therapy (CT) and sequential therapy
      (ST) have been proposed as alternative regimens. The aim of this study was to
      compare the eradication rate from using CT and ST in Korea. Methods: A literature
      review was performed on studies comparing the efficacy of CT and ST in Korea.
      Data were pooled to obtain the odds ratio (OR) of the eradication rate with 95%
      confidence intervals (CIs). The eradication rates were considered both on an
      intention-to-treat (ITT) and a per-protocol (PP) bases. Results: Six studies
      provided data on 1,897 Korean adult patients. The pooled OR was 1.382 (95% CI:
      1.031-1.853, p=0.031) for ITT analysis and 2.114 (95% CI: 1.502-2.974, p<0.001)
      for PP analysis. There was no difference in the rate of adverse events and
      compliances between the two regimens. Conclusions: The efficacy of CT was
      superior to ST in both ITT and PP analyses. Therefore, CT could be an excellent
      alternative regimen for the eradication of H. pylori as a first-line therapy in
      Korea.

PMID- 29361812
TI  - Associations between Atopic Dermatitis and Risk of Gastric Cancer: A Nationwide
      Population-based Study.
AB  - Background/Aims: Epidemiologic and clinical data indicate that allergies may be
      associated with reduced risks for several cancers; however, to date, only a few
      studies have examined the associations between allergies and gastric cancer. This
      study aimed to examine the associations between allergies and gastric cancer
      using a large population-based dataset. Methods: This cross-sectional study
      obtained data from the Korea National Health and Nutrition Examination Survey
      between 2010 and 2014, involving a total of 24,089 participants. The associations
      between allergies and gastric cancer were analyzed using univariable and
      multivariable logistic regression analyses with complex sampling, while adjusting
      for confounding factors that included age, sex, body mass index, smoking status,
      alcohol intake, and level of education. Results: Multivariable logistic
      regression analyses that were adjusted for the potential confounders determined
      that a history of allergic diseases tended to be associated with reduced risk of
      gastric cancer; however, this relationship was not statistically significant (any
      allergy: odds ratio [OR], 0.62; 95% confidence interval [CI], 0.34-1.12; atopic
      dermatitis: OR, 0.34; 95% CI, 0.50-1.72; allergic rhinitis: OR, 0.71; 95% CI,
      0.34-1.46; asthma: OR, 0.44; 95% CI, 0.15-1.29). Multivariable analysis showed
      that a history of atopic dermatitis was associated with reduced risk of gastric
      cancer in men (OR, 0.16; 95% CI, 0.03-0.75). Conclusions: This findings of this
      study suggest that individuals with allergies tend to have a reduced risk of
      gastric cancer, without a statistically significant association. Furthermore,
      atopic dermatitis was associated with reduced risk of gastric cancer,
      particularly in men.

PMID- 29361813
TI  - Ruptured Gas-forming Pyogenic Liver Abscess into the Peritoneal Cavity Treated
      Successfully with Medical Treatment.
AB  - Gas-forming pyogenic liver abscess (GFPLA) is very rare and has a very high
      mortality in case of rupture into the abdominal cavity, which usually require
      surgical treatment. We experienced a case of a ruptured GFPLA due to Klebsiella
      pneumoniae complicated with peritonitis and sepsis in a 68-year-old diabetic
      woman. Immediate and aggressive medical treatments including intravenous
      antibiotics, percutaneous drainage, and continuous renal replacement therapy
      dramatically improved the liver abscess, peritonitis, and metabolic problems. We
      report an unusual case of a ruptured GFPLA without surgical management, treated
      successfully with only medical treatment.

PMID- 29361814
TI  - Angiomyolipoma of the Liver without a Fat Component, Mimicking a Hepatocellular
      Carcinoma.
AB  - Angiomyolipoma (AML) is a rare benign mesenchymal tumor in the liver, which is
      composed of blood vessels, smooth muscle, and adipose cells. The proportion of
      each component varies, making a diagnosis difficult. This paper reports a case of
      AML in the liver without adipose tissue, mimicking a hepatocellular carcinoma
      (HCC), which was diagnosed by a surgical tissue biopsy. A 65-year-old woman was
      admitted for an evaluation of a hepatic mass that had been detected by
      ultrasonography. The serologic markers of viral hepatitis B and C were negative.
      The liver function tests and alpha fetoprotein level were within the normal
      limits. Magnetic resonance imaging revealed a 1.9 cm sized mass in segment 6 of
      the liver with early arterial enhancement and washout on the delayed phase
      accompanied by a rim-like enhancement, which is similar to the imaging findings
      of HCC. A frozen section examination during surgery indicated a hepatocellular
      neoplasm and suggested the possibility of HCC. On the other hand, the final
      pathologic diagnosis was epithelioid myoid type of AML with no adipose tissue
      component. The tumor cells were positive for human melanocyte B-45 and negative
      for cytokeratin and hepatocyte paraffin 1. This paper reports a very rare case of
      AML without adipose tissue in the liver mimicking HCC that was diagnosed by a
      surgical tissue biopsy.

PMID- 29361815
TI  - The NEAT Predictive Model for Survival in Patients with Advanced Cancer.
AB  - PURPOSE: We previously developed a model to more accurately predict life
      expectancy for stage IV cancer patients referred to radiation oncology. The goals
      of this study are to validate this model and to compare competing published
      models. Materials and Methods: From May 2012 to March 2015, 280 consecutive
      patientswith stage IV cancerwere prospectively evaluated by a single radiation
      oncologist. Patients were separated into training, validation and combined sets.
      TheNEAT model evaluated number of active tumors ("N"), Eastern Cooperative
      Oncology Group performance status ("E"), albumin ("A") and primary tumor site
      ("T"). The Odette Cancer Center model validated performance status, bone only
      metastases and primary tumor site. The Harvard TEACHH model investigated primary
      tumor type, performance status, age, prior chemotherapy courses, liver
      metastases, and hospitalization within 3 months. Cox multivariable analyses and
      logisticalregressionwere utilized to compare model performance. RESULTS: Number
      of active tumors, performance status, albumin, primary tumor site, prior
      hospitalizationwithin the last 3 months, and liver metastases predicted overall
      survival on uinvariate and multivariable analysis (p < 0.05 for all). The NEAT
      model separated patients into four prognostic groups with median survivals of
      24.9, 14.8, 4.0, and 1.2 months, respectively (p < 0.001). The NEAT model had a C
      index of 0.76 with a Nagelkerke's R2 of 0.54 suggesting good discrimination,
      calibration and total performance compared to competing prognostic models.
      CONCLUSION: The NEAT model warrants further investigation as a clinically useful
      approach to predict survival in patients with stage IV cancer.

PMID- 29361816
TI  - Negative Conversion of Progesterone Receptor Status after Primary Systemic
      Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer.
AB  - PURPOSE: Alteration of biomarker status after primary systemic therapy (PST) is
      occasionally found in breast cancer. This study was conducted to clarify the
      clinical implications of change of biomarker status in breast cancer patients
      treated with PST. Materials and Methods: The pre-chemotherapeutic biopsy and post
      chemotherapeutic resection specimens of 442 breast cancer patients who had
      residual disease after PST were included in this study. The association between
      changes of biomarker status after PST and clinicopathologic features of tumors,
      and survival of the patients, were analyzed. RESULTS: Estrogen receptor (ER),
      progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
      status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%)
      patients,respectively. ER and PR mainly underwent positive to negative
      conversion,whereas HER2 status underwent negative to positive conversion.
      Negative conversion of ER and PR status after PST was associated with reduced
      disease-free survival. Moreover, a decline in the Allred score for PR in post-PST
      specimens was significantly associated with poor clinical outcome of the
      patients. HER2 change did not have prognostic significance. In multivariate
      analyses, negative PR status after PST was found to be an independent adverse
      prognostic factor in the whole patient group, in the adjuvant endocrine therapy
      treated subgroup, and also in pre-PST PR positive subgroup. CONCLUSION: ER and
      HER2 status changed little after PST, whereas PR status changed significantly. In
      particular, negative conversion of PR status was revealed as a poor prognostic
      indicator, suggesting that re-evaluation of basic biomarkers is mandatory in
      breast cancer after PST for proper management and prognostication of patients.

PMID- 29361817
TI  - Circular RNA-ZFR Inhibited Cell Proliferation and Promoted Apoptosis in Gastric
      Cancer by Sponging miR-130a/miR-107 and Modulating PTEN.
AB  - PURPOSE: This study aimed to probe into the associations among circular RNA ZFR
      (circ-ZFR), miR-130a/miR-107, and PTEN, and to investigate the regulatory
      mechanism of circ-ZFR-miR-130a/miR-107-PTEN axis in gastric cancer (GC).
      Materials and Methods: GSE89143 microarray data used in the study were acquired
      from publicly available Gene Expression Omnibus database to identify
      differentially expressed circular RNAs inGC tissues. The expressions of circ-ZFR,
      miR-130a, miR-107, and PTEN were examined by real-time reverse transcription
      polymerase chain reaction, while PTEN protein expression was measured by western
      blot. The variation of GC cell proliferation and apoptosis was confirmed by cell
      counting kit-8 assay and flow cytometry analysis. The targeted relationships
      among circZFR, miR-130a/miR-107, and PTEN were predicted via bioinformatics
      analysis and demonstrated by dual-luciferase reporter assay and RNA
      immunoprecipitation assay. The impact of ZFR on gastric tumor was further
      verified in xenograft mice model experiment. RESULTS: Circ-ZFR and PTEN were low
      expressed whereas miR-107 and miR-130a were highexpressed in GC tissues and
      cells. There existed targeted relationships and interactions between miR-130a/miR
      107 and ZFR/PTEN. Circ-ZFR inhibited GC cell propagation, cell cycle and promoted
      apoptosis by sponging miR-107/miR-130a, while miR-107/miR-130a promoted GC cell
      propagation and impeded apoptosis through targeting PTEN. Circ-ZFR inhibited cell
      proliferation and facilitated apoptosis in GC by sponging miR-130a/miR-107 and
      modulating PTEN. Circ-ZFR curbed GC tumor growth and affected p53 protein
      expression in vivo. CONCLUSION: Circ-ZFR restrained GC cell proliferation,
      induced cell cycle arrest and promoted apoptosis by sponging miR-130a/miR-107 and
      regulating PTEN.

PMID- 29361818
TI  - Preclinical Study of Novel Curcumin Analogue SSC-5 Using Orthotopic Tumor
      Xenograft Model for Esophageal Squamous Cell Carcinoma.
AB  - PURPOSE: Tumor xenograft model is an indispensable animal cancer model. In
      esophageal squamous cell carcinoma (ESCC) research, orthotopic tumor xenograft
      model establishes tumor xenograft in the animal esophagus, which allows the study
      of tumorigenesis in its native microenvironment. Materials and Methods: In this
      study,we described two simple and reproducible methods to develop tumor xenograft
      at the cervical or the abdominal esophagus in nude mice by direct injection of
      ESCC cells in the esophageal wall. RESULTS: In comparing these two methods, the
      cervical one presented with more clinically relevant features, i.e., esophageal
      stricture, body weight loss and poor survival. In addition, the derived tumor
      xenografts accompanied a rapid growth rate and a high tendency to invade into the
      surrounding structures. This model was subsequently used to study the anti-tumor
      effect of curcumin, which is known for its potential therapeutic effects in
      various diseases including cancers, and its analogue SSC-5. SSC-5 was selected
      among the eight newly synthesized curcumin analogues based on its superior anti
      tumor effect demonstrated in an MTT cell proliferation assay and its effects on
      apoptosis induction and cell cycle arrest in cultured ESCC cells. Treatment of
      orthotopic tumor-bearing mice with SSC-5 resulted in an inhibition in tumor
      growth and invasion. CONCLUSION: Taken together, we have established a clinically
      relevant orthotopic tumor xenograft model that can serve as a preclinical tool
      for screening new anti-tumor compounds, e.g., SSC-5, in ESCC.

PMID- 29361819
TI  - Pembrolizumab for Refractory Metastatic Myxofibrosarcoma: A Case Report.
AB  - Myxofibrosarcoma is a rare tumor, refractory to cytotoxic chemotherapy and
      radiotherapy. Pembrolizumab is an innovative immunotherapy drug consisting of
      programmed death receptor ligand 1 antibody proven to be useful for numerous
      types of cancer cells. A patient had been diagnosed with metastatic
      myxofibrosarcoma, refractory to radiotherapy and conventional cytotoxic
      chemotherapy. The patient achieved a partial response during palliative
      chemotherapy with pembrolizumab for 14 cycles. To the best of our knowledge, this
      is the first case report demonstrating the efficacy of pembrolizumab for
      refractory myxofibrosarcoma.

PMID- 29361820
TI  - Projection of Breast Cancer Burden due to Reproductive/Lifestyle Changes in
      Korean Women (2013-2030) Using an Age-Period-Cohort Model.
AB  - PURPOSE: The aim of this study was to estimate the burden of breast cancer that
      can be attributed to rapid lifestyle changes in South Korea in 2013-2030.
      Materials and Methods: An age-period-cohort model was used to estimate the
      incidence and mortality. The Global Burden of Disease Study Group methodwas used
      to calculate the years of life lost and years lived with disability in breast
      cancer patients using a nationwide cancer registry. The population attributable
      riskswere calculated using meta-analyzed relative risk ratios and by assessing
      the prevalence of risk factors. RESULTS: Women's reproductive/lifestyle changes,
      including advanced maternal age at first childbirth (from 37 to 85 disability
      adjusted life years [DALYs] per 100,000 person-years), total period of
      breastfeeding (from 22 to 46 DALYs per 100,000 person-years), obesity (from 37 to
      61 DALYs per 100,000 person-years), alcohol consumption (from 19 to 39 DALYs per
      100,000 person-years), oral contraceptive use (from 18 to 27 DALYs per 100,000
      person-years), and hormone replacement therapy use (from 2 to 3 DALYs per 100,000
      person-years) were identified as factors likely to increase the burden of breast
      cancer from 2013 to 2030. Approximately, 34.2% to 44.3% of the burden of breast
      cancer could be avoidable in 2030 with reduction in reproductive/lifestyle risk
      factors. CONCLUSION: The rapid changes of age structure and lifestyle in South
      Korea during the last decade are expected to strongly increase the breast cancer
      burden over time unless the risk factors can be effectively modified.

PMID- 29361821
TI  - Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A
      Comparison between Primary Tumors and Corresponding Metastatic Lesions.
AB  - PURPOSE: Melanoma is a highly heterogeneous neoplasm, composed of subpopulations
      of tumor cells with distinct molecular and biological phenotypes and genotypes.
      In this study, to determine the genetic heterogeneity between primary and
      metastatic melanoma in Korean melanoma patients, we evaluated several well-known
      genetic alterations of melanoma. In addition, to elucidate the clinical relevance
      of each genetic alteration and heterogeneity between primary and metastatic
      lesions, clinical features and patient outcome were collected. Materials and
      Methods: In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT
      amplification data was acquired from an archived primary Korean melanoma cohort
      (KMC) of 188 patients. Among these patients, 43 patients were included for
      investigation of tumor heterogeneity between primary melanoma and its
      corresponding metastatic lesions. RESULTS: Overall incidence of genetic
      aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS
      mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of
      the uveal melanoma patients. Patients with BRAF mutation were associated with
      advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients,
      55.8% showed heterogeneity between primary and metastatic lesion. The frequency
      of BRAF mutation and KIT amplification significantly increased in the metastatic
      lesions compared to primary melanomas. <GNAQ/11 mutation showed 100% homogeneity
      in uveal melanoma patients. CONCLUSION: Our data demonstrated heterogeneity
      between primary melanomas and corresponding metastatic lesions for BRAF, NRAS
      mutation and KIT amplification. However, GNAQ/11 mutation was genetically
      homogeneous between primary and metastatic melanoma lesions in uveal melanoma.

PMID- 29361822
TI  - Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates
      with Poor Prognosis in Colorectal Cancer.
AB  - PURPOSE: Molecular treatments targeting epidermal growth factor receptors (EGFRs)
      are important strategies for advanced colorectal cancer (CRC). However,
      clinicopathologic implications of EGFRs and EGFR ligand signaling have not been
      fully evaluated. We evaluated the expression of EGFR ligands and correlation with
      their receptors, clinicopathologic factors, and patients' survival with CRC.
      Materials and Methods: The expression of EGFR ligands, including heparin binding
      epidermal growth factor-like growth factor (HBEGF), transforming growth factor
      (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331
      consecutive CRC samples using mRNA in situ hybridization (ISH). We also evaluated
      the expression status of EGFR, human epidermal growth factor receptor 2 (HER2),
      HER3, and HER4 using immunohistochemistry and/or silver ISH. RESULTS: Unlike low
      incidences of TGF (38.1%), betacellulin (7.9%), and EGF (2.1%), HBEGF expression
      was noted in 62.2% of CRC samples. However, the expression of each EGFR ligand
      did not reveal significant correlations with survival. The combined analyses of
      EGFR ligands and EGFR expression indicated that the ligands-/EGFR+ group showed a
      significant association with the worst disease-free survival (DFS; p=0.018) and
      overall survival (OS; p=0.005). It was also an independent, unfavorable
      prognostic factor for DFS (p=0.026) and OS (p=0.007). Additionally, HER4 nuclear
      expression, regardless of ligand expression, was an independent, favorable
      prognostic factor for DFS (p=0.034) and OS (p=0.049), by multivariate analysis.
      CONCLUSION: Ligand-independent EGFR overexpression was suggested to have a
      significant prognostic impact; thus, the expression status of EGFR ligands, in
      addition to EGFR, might be necessary for predicting patients' outcome in CRC.

PMID- 29361823
TI  - Trends in Gastric Cancer Incidence According to the Clinicopathological
      Characteristics in Korea, 1999-2014.
AB  - PURPOSE: The aim of this study was to evaluate recent trends in gastric cancer
      incidence according to the age, sex, and tumor location in the Korean population.
      Materials and Methods: Using data from the Korea Central Cancer Registry between
      1999 and 2014, gastric cancer incidence, annual percent changes, and male-to
      female incidence rate ratios (IRRs) according to tumorlocationwere determined.
      The distribution of disease extent according to the tumor location and its
      changes between 2006 and 2014 were also analyzed. RESULTS: Incidence of gastric
      cancer was stable until 2011 and decreased between 2011 and 2014. The age
      standardized incidence rate of gastric cancer was 43.6 (per 100,000) in 1999 and
      35.8 in 2014. The proportion of cardia/fundus cancer remained stable (5.9% to
      7.1%), and that of body cancer increased (35.3% to 43.2%). The male-to-female IRR
      decreased in most age groups, except for those in their 60s. In the distribution
      of disease extent, the proportion of localized disease increased, and regional
      and distant disease decreased in all tumor locations (53.9% to 66.0%, 31.4% to
      22.5%, and 14.8% to 11.5%, respectively; p < 0.001). For histological type, the
      proportion of carcinoid tumor and non-epithelial tumor increased (0.3% to 1.0%,
      and 0.8% to 1.4%, respectively). CONCLUSION: In the 15 years from 1999 through
      2014, age-standardized incidence of gastric cancer started to decrease from 2012,
      and the proportion of cardia/fundus cancer remained unchanged. The trend of
      increasing localized cancer was observed in all tumor locations.

PMID- 29361824
TI  - Structural and Kinetic Visualization of the Protein Corona on Bioceramic
      Nanoparticles.
AB  - Bioceramic nanoparticles exhibit excellent features that enable them to function
      as an ideal material for hard tissue engineering. However, to fully understand
      their behavior, it is of crucial importance to understand their behavior within
      the fluids of the human body. To achieve this goal, we have studied the
      interaction between hydroxyapatite nanorods (HA) and bovine serum albumin (BSA).
      First, we describe the surface morphology of the nanoparticle. Then, the main
      characteristics of the physiological interplay of BSA and the hydroxyapatite
      nanoparticle are presented by using a battery of techniques: ITC, zeta potential,
      UV-vis, fluorescence, and CD. Experimental data was analyzed by developing
      specific approaches to determining important parameters such as rates,
      affinities, and stochiometries of protein associated with the nanoparticles. ITC
      has been confirmed as a powerful technique for determining the affinity, binding,
      and thermodynamics of BSA-nanoparticle interactions. Careful quantitative
      assessment of the kinetic properties of the adsorption were revealed by UV-vis
      and fluorescence measurements. Finally, CD measurements highlight the important
      role of protein flexibility in these kinds of systems.

PMID- 29361825
TI  - Erythritol Attenuates Postprandial Blood Glucose by Inhibiting alpha-Glucosidase.
AB  - Diabetes mellitus (DM) is a serious metabolic disorder, where impaired
      postprandial blood glucose regulation often leads to severe health complications.
      The natural chemical erythritol is a C4 polyol approved by the U.S. Food and Drug
      Administration for use as a sweetener. Here, we examined a potential role for
      erythritol in the control of postprandial blood glucose levels in DM. An anti
      postprandial hyperglycemia effect upon erythritol administration (500 mg kg-1)
      was demonstrated in alloxan-induced DM model mice by monitoring changes in blood
      glucose after intragastric administration of drugs and starch. We also found that
      erythritol most likely exerts its anti-postprandial hyperglycemic activities by
      inhibiting alpha-glucosidase in a competitive manner. This was supported by
      enzyme activity assays and molecular modeling experiments. In the latter
      experiments, it was possible to successfully dock erythritol into the catalytic
      pocket of alpha-glucosidase, with the resultant interaction likely driven by
      electrostatic interactions involving Asp215, Asp69, and Arg446 residues. This
      study suggests that erythritol may not only serve as a glucose substitute but
      also be a useful agent in the treatment of DM to help manage postprandial blood
      glucose levels.

PMID- 29361827
TI  - Introduction: Sustainable Chemistry.

PMID- 29361826
TI  - Direct Mapping of Heterogeneous Surface Coverage in DNA-Functionalized Gold
      Surfaces with Correlated Electron and Fluorescence Microscopy.
AB  - The characterization of biofunctionalized surfaces such as alkanethiol self
      assembled monolayers (SAMs) on gold modified with DNA or other biomolecules is a
      challenging analytical problem, and access to a routine method is desirable.
      Despite substantial investigation from structural and mechanistic perspectives,
      robust and high-throughput metrology tools for SAMs remain elusive but essential
      for the continued development of these devices. We demonstrate that scanning
      electron microscopy (SEM) can provide image contrast of the molecular interface
      during SAM functionalization. The high-speed, large magnification range, and ease
      of use make this widely available technique a powerful platform for measuring the
      structure and composition of SAM surfaces. This increased throughput allows for a
      better understanding of the nonideal spatial heterogeneity characteristic of SAMs
      utilized in real-world conditions. SEM image contrast is characterized through
      the use of fluorescently labeled DNA, which enables correlative SEM and
      fluorescence microscopy. This allows identification of the DNA-modified regions
      at resolutions that approach the size of the biomolecule. The effect of electron
      beam irradiation dose is explored, which leads to straightforward lithographic
      patterning of DNA SAMs with nanometer resolution and with control over the
      surface coverage of specifically adsorbed DNA.

PMID- 29361829
TI  - Barriers to Hospice Care in Trauma Patients: The Disparities in End-of-Life Care.
AB  - INTRODUCTION: End-of-life and palliative care are important aspects of trauma
      care and are not well defined. This analysis evaluates the racial and
      socioeconomic disparities in terms of utilization of hospice services for
      critically ill trauma patients. METHODS: Trauma patients >=15 years old from 2012
      to 2015 were queried from the National Trauma Databank. Chi-square and
      multivariate logistic regression analyses for disposition to hospice were
      performed after controlling for age, gender, comorbidities, injury severity,
      insurance, race, and ethnicity. Negative binomial regression analysis with
      margins for length of stay (LOS) was calculated for all patients discharged to
      hospice. RESULTS: Chi-square analysis of 2 966 444 patient's transition to
      hospice found patients with cardiac disease, bleeding and psychiatric disorders,
      chemotherapy, cancer, diabetes, cirrhosis, respiratory disease, renal failure,
      cirrhosis, and cerebrovascular accident (CVA) affected transfer ( P < .0001).
      Logistic regression analysis after controlling for covariates showed uninsured
      patients were discharged to hospice significantly less than insured patients
      (odds ratio [OR]: 0.71; P < .0001). Asian, African American, and Hispanic
      patients all received less hospice care than Caucasian patients (OR: 0.65, 0.60,
      0.73; P < .0001). Negative binomial regression analysis with margins for LOS
      showed Medicare patients were transferred to hospice 1.2 days sooner than insured
      patients while uninsured patients remained in the hospital 1.6 days longer ( P <
      .001). When compare to Caucasians, African Americans patients stayed 3.7 days
      longer in the hospital and Hispanics 2.4 days longer prior to transfer to hospice
      ( P < .0001). In all patients with polytrauma, African Americans stayed 4.9 days
      longer and Hispanics 2.3 days longer as compared to Caucasians ( P < .0001).
      CONCLUSIONS: Race and ethnicity are independent predictors of a trauma patient's
      transition to hospice care and significantly affect LOS. Our data demonstrate
      prominent racial and socioeconomic disparities exist, with uninsured and minority
      patients being less likely to receive hospice services and having a delay in
      transition to hospice care when compared to their insured Caucasian counterparts.

PMID- 29361831
TI  - Troublesome Knowledge: A New Approach to Quality Assurance in Mental Health
      Nursing Education.
AB  - Background Quality assurance and quality enhancement processes in nursing
      education are vital to the establishment of a strong program. Existing quality
      assurance methods in nursing education such as professional self-regulation and
      external examination rely on provincial and national nursing associations for
      evaluation, putting minimal responsibility and accountability on internal program
      examiners. Threshold concepts and troublesome knowledge provide a framework as
      outlined by Land that utilizes internal examiners from both student and faculty
      groups and represents an alternative to traditional quality assurance in nursing
      education. Purpose To identify troublesome mental health nursing content in a
      nursing curriculum by exploring students and faculty perspectives. Method A
      sequential mixed methods design that utilized surveys and focus groups to explore
      student and faculty perspectives on troublesome mental health nursing content.
      Results The project data were able to be organized into five main content themes
      that were identified as being troublesome: the spectrum of mental illness,
      therapeutic relationships and boundaries, praxis, professionalism in nursing, and
      brain chemistry and its management. Conclusion The findings from this project are
      unique to the program of review but show the potential of this new approach to
      quality assurance and program enhancement initiatives in nursing education.

PMID- 29361830
TI  - Is there a learning effect when the 6-minute walk test is repeated in people with
      suspected pulmonary hypertension?
AB  - The aim of the study was to determine if there was a difference in 6-minute walk
      distance (6MWD) when two 6-minute walk tests (6MWTs) were performed at the
      initial assessment prior to attendance at the pulmonary hypertension (PH) clinic
      and at the 6-month follow-up. Two 6MWTs were performed at both visits on a 32-m
      continuous track in the physiotherapy hospital outpatient setting using standard
      instructions and encouragement. Two hundred and fourteen participants completed
      two 6MWTs at the initial assessment and 71 participants at the 6-month follow-up
      (mean (standard deviation) age: 57 (16) years; body mass index: 27 (6) kg/m2).
      Using the better 6MWT, the mean distances walked were 429 (136) and 447 (130) m,
      respectively. There was a significant increase in 6MWD when a second 6MWT was
      performed at initial assessment (mean difference [95% confidence interval (CI)]:
      19 m (14-24), p < 0.001) and at the follow-up (mean difference [95% CI]: 19 m (10
      27), p < 0.001) but not in those who walked <300 m at the initial assessment
      (mean difference [95% CI]: 9 m (-5 to 22), p = 0.208). There were no adverse
      events during testing. Prior to attendance at the PH Clinic when people are asked
      to perform the 6MWT for the first time and at the 6-month follow-up, two walk
      tests should be performed in order to eliminate a learning effect and to ensure
      accuracy of measurement.

PMID- 29361832
TI  - Role of Endoplasmic Reticulum-Mediated Ca2+ Signaling in Neuronal Cell Death.
AB  - SIGNIFICANCE: Properly controlled intracellular Ca2+ dynamics is crucial for
      regulation of neuronal function and survival in the central nervous system. The
      endoplasmic reticulum (ER), a major intracellular Ca2+ store, plays a critical
      role as a source and sink for neuronal Ca2+. Recent Advances: Accumulating
      evidence indicates that disrupted ER Ca2+ signaling is involved in neuronal cell
      death under various pathological conditions, providing novel insight into
      neurodegenerative disease mechanisms. CRITICAL ISSUES: We summarize current
      knowledge concerning the relationship between abnormal ER Ca2+ dynamics and
      neuronal cell death. We also introduce recent technical advances for probing ER
      intraluminal Ca2+ dynamics with unprecedented spatiotemporal resolution. FUTURE
      DIRECTIONS: Further studies on ER Ca2+ signaling are expected to provide progress
      for unmet medical needs in neurodegenerative disease. Antioxid. Redox Signal. 29,
      1147-1157.

PMID- 29361833
TI  - Are pilot trials useful for predicting randomisation and attrition rates in
      definitive studies: A review of publicly funded trials.
AB  - BACKGROUND/AIMS: External pilot trials are recommended for testing the
      feasibility of main or confirmatory trials. However, there is little evidence
      that progress in external pilot trials actually predicts randomisation and
      attrition rates in the main trial. To assess the use of external pilot trials in
      trial design, we compared randomisation and attrition rates in publicly funded
      randomised controlled trials with rates in their pilots. METHODS: Randomised
      controlled trials for which there was an external pilot trial were identified
      from reports published between 2004 and 2013 in the Health Technology Assessment
      Journal. Data were extracted from published papers, protocols and reports. Bland
      Altman plots and descriptive statistics were used to investigate the agreement of
      randomisation and attrition rates between the full and external pilot trials.
      RESULTS: Of 561 reports, 41 were randomised controlled trials with pilot trials
      and 16 met criteria for a pilot trial with sufficient data. Mean attrition and
      randomisation rates were 21.1% and 50.4%, respectively, in the pilot trials and
      16.8% and 65.2% in the main. There was minimal bias in the pilot trial when
      predicting the main trial attrition and randomisation rate. However, the
      variation was large: the mean difference in the attrition rate between the pilot
      and main trial was -4.4% with limits of agreement of -37.1% to 28.2%. Limits of
      agreement for randomisation rates were -47.8% to 77.5%. CONCLUSION: Results from
      external pilot trials to estimate randomisation and attrition rates should be
      used with caution as comparison of the difference in the rates between pilots and
      their associated full trial demonstrates high variability. We suggest using
      internal pilot trials wherever appropriate.

PMID- 29361834
TI  - The Effect of Moderate- Versus High-Intensity Resistance Training on Systemic
      Redox State and DNA Damage in Healthy Older Women.
AB  - : This study investigated effects of a 16-week progressive resistance training
      program (RTP) with elastic bands at two different intensities on systemic redox
      state, DNA damage, and physical function in healthy older women. METHODS:
      Participants were randomly assigned to the high-intensity group (HIGH; n = 39),
      moderate-intensity group (MOD; n = 31), or control group (CG; n = 23). The
      exercise groups performed an RTP twice a week with three to four sets of 6 (HIGH)
      or 15 (MOD) repetitions of six overall body exercises at a perceived exertion
      rate of 8-9 on the OMNI-Resistance Exercise Scale for use with elastic bands.
      Thiol redox state was determined by reduced glutathione (GSH), oxidized
      glutathione (GSSG), and GSSG/GSH in blood mononuclear cells. Degree of DNA damage
      was assessed by presence of the oxidized DNA base molecule 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-OHdG) in urine. Physical function monitoring was based on the
      arm curl, chair stand, up and go, and 6-min walk tests. RESULTS: The HIGH group
      showed a significant increase in 8-OHdG (+71.07%, effect size [ES] = 1.12) and a
      significant decrease in GSH (-10.91, ES = -0.69), while the MOD group showed a
      significant decrease in 8-OHdG levels (-25.66%, ES = -0.69) with no changes in
      thiol redox state. GSH levels differed significantly between the HIGH and CG
      groups posttest. The exercise groups showed significant improvements in physical
      function with no differences between groups. CONCLUSION: RTP at a moderate rather
      than high intensity may be a better strategy to reduce DNA damage in healthy
      older women while also increasing independence.

PMID- 29361835
TI  - Activity monitoring in men's college soccer: a single season longitudinal study.
AB  - Performance in soccer has been characterized previously using time-motion
      analyses; however, it is unclear if men's college soccer shares performance
      characteristics with women's college or men's professional soccer. The purpose of
      this study was to compare proportions of matches spent walking, jogging, running,
      and sprinting in men's college soccer. Twenty-two male college soccer players
      wore global positioning system units during matches. Proportions of walking,
      jogging, running, high-speed running, and sprinting were calculated for each
      player based on time period (first half, second half, extra time) and outcome
      (win, loss, tie). Multivariate analyses of variance were run for each time period
      to compare positions. Means, 95% confidence intervals, and effect sizes were
      calculated for each position based on time period and match outcome. There were
      differences in low-speed and high-speed activities based on position, with
      forwards and midfielders demonstrating increased high-speed activities.
      Positional differences may require different physiological profiles and should be
      a consideration during training.

PMID- 29361836
TI  - Emotional Well-Being Following a Later Life Career Change: The Roles of Agency
      and Resources.
AB  - More individuals are attempting career changes in later life, as an increasing
      number of people face precarious retirement prospects. Although many of these
      older job seekers eventually find new livelihoods, little is known about their
      emotional well-being subsequent to these changes. Using the 2014 American
      Institute for Economic Research Older Worker Survey, we evaluate the
      contributions of demographic characteristics, agency, and resources when
      estimating three measures of emotional well-being following a successful later
      life career change ( n = 337). We found that having financial resources during
      the career transition was associated with all three positive emotional outcomes,
      while family support and intentionality were also associated with positive
      emotions. Conversely, prior job prestige and purposeful job training had no
      relationships with subsequent well-being. These results suggest that later life
      career changes, despite their challenges, often result in positive emotional
      outlooks-for those who have the resources to support them.

PMID- 29361837
TI  - Cortical surface area reduction in identification of subjects at high risk for
      post-traumatic stress disorder: A pilot study.
AB  - OBJECTIVE:: Victims of motor vehicle accidents often develop post-traumatic
      stress disorder, which causes significant social function loss. For the
      difficulty in treating post-traumatic stress disorder, identification of subjects
      at high risk for post-traumatic stress disorder is essential for providing
      possible intervention. This paper aims to examine the cortical structural traits
      related to susceptibility to post-traumatic stress disorder. METHODS:: To address
      this issue, we performed structural magnetic resonance imaging study in motor
      vehicle accident victims within 48 hours from the accidents. A total of 70
      victims, available for both clinical and magnetic resonance imaging data,
      enrolled in our study. Upon completion of 6-month follow-up, 29 of them developed
      post-traumatic stress disorder, while 41 of them didn't. At baseline, voxelwise
      comparisons of cortical thickness, cortical area and cortical volume were
      conducted between post-traumatic stress disorder group and trauma control group.
      RESULTS:: As expected, several reduced cortical volume within frontal-temporal
      loop were observed in post-traumatic stress disorder. For cortical thickness, no
      between-group differences were observed. There were three clusters in left
      hemisphere and one cluster in right hemisphere showing decreased cortical area in
      post-traumatic stress disorder patients, compared with trauma controls. Peak
      voxels of the three clusters in left hemisphere were separately located in
      superior parietal cortex, insula and rostral anterior cingulate cortex.
      CONCLUSION:: The finding of reduced surface area of left insula and left rostral
      anterior cingulate cortex suggests that shrinked surface area in motor vehicle
      accident victims could act as potential biomarker of subjects at high risk for
      post-traumatic stress disorder.

PMID- 29361838
TI  - Interventions minimizing fatigue in children/adolescents with cancer: An
      integrative review.
AB  - Fatigue is among the most common, debilitating, and distressing symptoms
      associated with chronic condition in pediatric population. The purpose of this
      study was to identify non-pharmacological fatigue interventions in children and
      adolescents with cancer. For this, we carried out an integrative review of the
      literature from January 2000 to December 2016. A comprehensive search of four
      databases was conducted: Cumulative Index to Nursing and Allied Health
      Literature, Psychology Information, Medline via PubMed, and Web of Science.
      Randomized controlled trial, quasi-experimental, case-control and cohort studies
      were included in this review. Thirteen relevant studies were included for
      analysis. Seven papers reported positive outcomes for exercise, exercise plus
      leisure activities, healing touch and acupressure. In another six papers using
      exercise, exercise plus psychological intervention and massage, no effectiveness
      was found. Effective management of fatigue in children and adolescents is
      important but research in this area is limited, so the results of this review
      should be interpreted cautiously. Future researchers are encouraged to test the
      effective interventions in homogenous cancer populations and in other groups
      where fatigue is a common concern.

PMID- 29361839
TI  - Family management affecting transition readiness and quality of life of Chinese
      children and young people with chronic diseases.
AB  - Transition from pediatric to adult health care is a key milestone for children
      and young people (CYP) with chronic conditions. Family management (FM) and self
      management are two important concepts during the process. This study aimed to
      explore the relationships between FM, self-management and transition readiness,
      and quality of life (QoL), and identify the potential CYP or family factors
      influencing the relationships. Data about FM, self-management and transition
      readiness, QoL, and various contextual factors were collected from 268 caregiver
      child pairs. Structural equation modeling was used to examine the relationships
      between all variables. Results revealed that the easy aspects of FM mediated the
      relationships between the challenging aspects of FM, self-management and
      transition readiness, and QoL of CYP. Self-management and transition readiness
      mediated the relationship between the easy aspects of FM and QoL. Contextual
      factors indirectly influenced CYP's transition readiness and QoL through
      different aspects of FM. The results imply that to ensure the smooth transition
      from pediatric to adult health care and improve the CYP's QoL, strengthening
      CYP's independence and self-management competencies, combined with the support of
      the easy aspects of FM, seem to be useful strategies to increase CYP's readiness
      for transfer.

PMID- 29361840
TI  - Safety and Efficacy of OXB-202, a Genetically Engineered Tissue Therapy for the
      Prevention of Rejection in High-Risk Corneal Transplant Patients.
AB  - Due to both the avascularity of the cornea and the relatively immune-privileged
      status of the eye, corneal transplantation is one of the most successful clinical
      transplant procedures. However, in high-risk patients, which account for >20% of
      the 180,000 transplants carried out worldwide each year, the rejection rate is
      high due to vascularization of the recipient cornea. The main reason for graft
      failure is irreversible immunological rejection, and it is therefore unsurprising
      that neovascularization (NV; both pre and post grafting) is a significant risk
      factor for subsequent graft failure. NV is thus an attractive target to prevent
      corneal graft rejection. OXB-202 (previously known as EncorStat(r)) is a donor
      cornea modified prior to transplant by ex vivo genetic modification with genes
      encoding secretable forms of the angiostatic human proteins, endostatin and
      angiostatin. This is achieved using a lentiviral vector derived from the equine
      infectious anemia virus called pONYK1EiA, which subsequently prevents rejection
      by suppressing NV. Previously, it has been shown that rabbit donor corneas
      treated with pONYK1EiA substantially suppress corneal NV, opacity, and subsequent
      rejection in an aggressive rabbit model of cornea graft rejection. Here, efficacy
      data are presented in a second rabbit model, which more closely mirrors the
      clinical setting for high-risk corneal transplant patients, and safety data from
      a 3-month good laboratory practice toxicology and biodistribution study of
      pONYK1EiA-modified rabbit corneas in a rabbit corneal transplant model. It is
      shown that pONYK1EiA-modified rabbit corneas (OXB-202) significantly reduce
      corneal NV and the rate of corneal rejection in a dose-dependent fashion, and are
      tolerated with no adverse toxicological findings or significant biodistribution
      up to 13 weeks post surgery in these rabbit studies. In conclusion, angiogenesis
      is a valid target to prevent corneal graft rejection in a high-risk setting, and
      transplanted genetically modified corneas are safe and well-tolerated in an
      animal model. These data support the evaluation of OXB-202 in a first-in-human
      trial.

PMID- 29361841
TI  - Cross-Sectional Analysis of the Distal Fibular Intramedullary Canal: A Cadaveric
      Evaluation.
AB  - : Fractures of the distal fibula secondary to rotational ankle injuries are one
      of the most common injuries requiring surgical intervention. The aim of this
      study was to describe the anatomy of the distal fibular medullary canal as a
      means of aiding in surgical management with an intramedullary device. Twenty
      fresh cadaveric below-knee specimens (group 1, 10 in 2015, group 2, 10 in 2016)
      were dissected to expose the distal fibular. Fifteen (10 mm each) segments were
      sectioned with a sagittal saw from the distal tip proximally and measured with a
      digital caliper. In group I, the widest and narrowest fibular diameter was at the
      20-mm interval (mean 15.02 mm) and 90-mm interval (mean 3.51 mm), respectively.
      From 70 to 120 mm, the mean diameter was less than 4.0 mm. In group 2, the widest
      and narrowest diameter was at the 20-mm interval (mean 15.05 mm) and 100-mm
      interval (mean 4.33 mm), respectively. From 70 to 140 mm, the mean diameter was
      less than 5.0 mm. The combined mean diameter at the 60- to 80-mm intervals were
      4.99 +/- 1.70, 4.35 +/- 1.63, and 4.02 +/- 1.35 mm, respectively. Based on our
      investigation, we propose an intramedullary device diameter of 4.5 to 5.0 mm in
      diameter with a length of 60 to 80 mm may provide most appropriate bony purchase
      to achieve acceptable cortical contact for expected osseous compression. LEVELS
      OF EVIDENCE: Level IV: Cadaveric case series.

PMID- 29361842
TI  - Beta carotene-loaded zein nanoparticles to improve the biopharmaceutical
      attributes and to abolish the toxicity of methotrexate: a preclinical study for
      breast cancer.
AB  - Beta carotene (betaC) loaded nanoparticles of zein (betaC-NPs) were developed
      using modified phase separation technique. betaC-NPs were prepared using
      different zein concentration and optimized formulation was selected on the basis
      of micromeritics properties and entrapment efficiency. Further, betaC-NPs were
      evaluated for in vitro release, in vitro cell-survival, cellular localization and
      apoptosis induced in MCF-7 cells. The combined effect of the betaC and its
      nanoparticulate counterpart with MTX was evaluated thereafter for cytotoxicity
      and apoptotic activity in MCF-7 cells. In comparison to free betaC, the betaC-NPs
      demonstrated noteworthy improvement in various biopharmaceutical attributes viz
      Cmax (~2.3-folds), AUCtotal (2.7-folds), t1/2 (~1.5 folds) and MRT (~1.5 folds),
      further indicating the remarkable increment in oral bioavailability of betaC
      after incorporation in zein nanoparticles. The anti-tumour potential of prepared
      betaC-NPs and effects of free betaC and betaC-NPs were investigated upon
      anticancer efficacy of methotrexate (MTX) in experimentally induced breast cancer
      rat model. Protective role of betaC on MTX-associated hepatic toxicity in wistar
      rats was also determined using haematological and histopathological approaches.
      In a nutshell, zein nanoparticles improved the cellular uptake, cytotoxicity and
      exhibited enhanced oral biopharmaceutical performance of betaC. This combination
      regimen could also be promising platform to facilitate the therapeutic benefits
      of anticancer agents.

PMID- 29361844
TI  - Nanoflowers: the future trend of nanotechnology for multi-applications.
AB  - Nanoflowers are a newly developed class of nanoparticles showing structure
      similar to flower and gaining much attention due to their simple method of
      preparation, high stability and enhance efficiency. This article focuses on
      advantages, disadvantages, method of synthesis, types and applications of
      nanoflowers with futuristic approaches. The applications of nanoflower include
      its use as a biosensor for quick and precise detection of conditions like
      diabetes, Parkinsonism, Alzheimer, food infection, etc. Nanoflowers have been
      revealed for site-specific action and controlled delivery of drugs. The extended
      applications of nanoflowers cover purification of enzyme, removal of dye and
      heavy metal from water, gas-sensing using nickel oxide. Recent investigation
      shows 3 D structure of nanoflowers for enhancing surface sensitivity using Raman
      spectroscopy. This nanoflower system will act as a smart material in the near
      future due to high surface-to-volume ratio and enhance adsorption efficiency on
      its petals.

PMID- 29361843
TI  - Use of online recruitment strategies in a randomized trial of cancer survivors.
AB  - BACKGROUND/AIMS: Despite widespread Internet adoption, online advertising remains
      an underutilized tool to recruit participants into clinical trials. Whether
      online advertising is a cost-effective method to enroll participants compared to
      other traditional forms of recruitment is not known. METHODS: Recruitment for the
      Survivorship Promotion In Reducing IGF-1 Trial, a community-based study of cancer
      survivors, was conducted from June 2015 through December 2016 via in-person
      community fairs, advertisements in periodicals, and direct postal mailings. In
      addition, "Right Column" banner ads were purchased from Facebook to direct
      participants to the Survivorship Promotion In Reducing IGF-1 Trial website.
      Response rates, costs of traditional and online advertisements, and demographic
      data were determined and compared across different online and traditional
      recruitment strategies. Micro-trials optimizing features of online advertisements
      were also explored. RESULTS: Of the 406 respondents to our overall outreach
      efforts, 6% (24 of 406) were referred from online advertising. Facebook
      advertisements were shown over 3 million times (impressions) to 124,476 people,
      which resulted in 4401 clicks on our advertisement. Of these, 24 people
      ultimately contacted study staff, 6 underwent prescreening, and 4 enrolled in the
      study. The cost of online advertising per enrollee was $794 when targeting a
      general population versus $1426 when accounting for strategies that specifically
      targeted African Americans or men. By contrast, community fairs, direct mail, or
      periodicals cost $917, $799, or $436 per enrollee, respectively. Utilization of
      micro-trials to assess online ads identified subtleties (e.g. use of an
      advertisement title) that substantially impacted viewer interest in our trial.
      CONCLUSION: Online advertisements effectively directed a relevant population to
      our website, which resulted in new enrollees in the Survivorship Promotion In
      Reducing IGF-1 Trial at a cost comparable to traditional methods. Costs were
      substantially greater with online recruitment when targeting under-represented
      populations, however. Additional research using online micro-trial tools is
      needed to evaluate means of more precise recruitment to improve yields in under
      represented groups. Potential gains from faster recruitment speed remain to be
      determined.

PMID- 29361845
TI  - The Impact of Partnership Status on Diabetes Control and Self-Management
      Behaviors.
AB  - According to the Centers for Disease Control and Prevention, diabetes affects
      29.1 million people in the United States. Marriage has been suggested to have a
      protective effect on overall health outcomes, but few studies have evaluated the
      role of partnership status on patients with type 2 diabetes. This study aimed to
      assess this role of partnership status on diabetes control and self-management
      behaviors. Patients with type 2 diabetes taking at least one oral hypoglycemic
      agent were assessed over a 3-month period to measure hemoglobin A1c (HbA1c)
      changes and adherence to medication, exercise, diet, and glucose monitoring.
      Partnered participants were more likely to adhere to their medications, but there
      was no significant difference in HbA1c changes over 3 months or exercise, diet,
      or glucose monitoring adherence. This study suggests that being partnered
      improves medication adherence; further analysis with a larger population is
      required to fully assess the role of partner support for patients with type 2
      diabetes.

PMID- 29361846
TI  - A Community-Partnered Approach to Inform a Culturally Relevant Health Promotion
      Intervention for Stroke.
AB  - BACKGROUND: The purpose of this study was to generate information from
      multiethnic, high-risk communities to inform the creation of culturally relevant
      health promotion intervention for increasing early hospital arrival after stroke.
      METHODS: The study employed a qualitative design, using focus groups with African
      American, Caucasian, and Hispanic adults in two Chicago community areas. The
      study relied heavily on stakeholder input in creating the focus group guide,
      recruiting participants, and interpreting the analysis. RESULTS: Six focus groups
      gained information from 51 participants, including insights and perspective on
      participants' stroke experience and knowledge as well as on facilitators and
      barriers to calling 9-1-1. Qualitative analysis uncovered themes relating to risk
      factors, symptoms, knowledge of stroke mechanisms, experience of acute stroke,
      help seeking, stroke education, recovery, treatment, and emotions. Communities
      were closely aligned in their knowledge of stroke, but had differing ideas around
      stroke education and dissemination of education. DISCUSSION: This study
      identified nuances in real-world barriers to receiving acute stroke services in
      minority and disadvantaged communities in Chicago neighborhoods. Our findings
      indicated significant amount of variation by race/ethnicity and, in particular, a
      lack of similarities based on race/ethnic groups in different communities. These
      findings underscore the importance of working with communities to fully
      understand the community-level dynamics that occur.

PMID- 29361847
TI  - Intrasexual Competition and Height in Adolescents and Adults.
AB  - Intrasexual competition can be defined as the struggle between members of one sex
      to increase their access to members of the other sex as sexual partners. In our
      species, height is a sexually dimorphic trait probably involved in both
      intrasexual and intersexual selective processes. In the present research, we
      examined the relationship between height and individual differences in
      intrasexual competitiveness (i.e., the tendency to view same-sex interactions in
      general in competitive terms) in two populations of adolescents and adults of
      both sexes in Chile. According to our first prediction, among both adolescent and
      adult men, height was negatively associated with intrasexual competitiveness. In
      contrast, among women, height was not linearly nor quadratically related with
      intrasexual competitiveness as previously reported. Finally, adolescent men and
      women showed increased levels of intrasexual competitiveness compared to adult
      same-sex counterparts. Our results suggest that height is a relevant trait in
      mating competition among men. The lack of relationship between height and
      intrasexual competitiveness in women may suggest that the role of height in women
      mating competition may be more complex and mediated by other variables.

PMID- 29361848
TI  - Care Pathways Before First Diagnosis of a Psychotic Disorder in Adolescents and
      Young Adults.
AB  - OBJECTIVE: The authors sought to describe patterns of health care use prior to
      first diagnosis of a psychotic disorder in a population-based sample. METHOD:
      Electronic health records and insurance claims from five large integrated health
      systems were used to identify 624 patients 15-29 years old who received a first
      diagnosis of a psychotic disorder in any care setting and to record health
      services received, diagnoses assigned, and medications dispensed during the
      previous 36 months. Patterns of utilization were compared between patients
      receiving a first diagnosis of a psychotic disorder and matched samples of
      general health system members and members receiving a first diagnosis of unipolar
      depression. RESULTS: During the year before a first psychotic disorder diagnosis,
      29% of patients had mental health specialty outpatient care, 8% had mental health
      inpatient care, 24% had emergency department mental health care, 29% made a
      primary care visit with a mental health diagnosis, and 60% received at least one
      mental health diagnosis (including substance use disorders). Compared with
      patients receiving a first diagnosis of unipolar depression, those with a first
      diagnosis of a psychotic disorder were modestly more likely to use all types of
      health services and were specifically more likely to use mental health inpatient
      care (odds ratio=2.96, 95% CI=1.97-4.43) and mental health emergency department
      care (rate ratio=3.74, 95% CI=3.39-4.53). CONCLUSIONS: Most patients receiving a
      first diagnosis of a psychotic disorder had some indication of mental health care
      need during the previous year. General use of primary care or mental health
      services, however, does not clearly distinguish people who later receive a
      diagnosis of a psychotic disorder from those who later receive a diagnosis of
      unipolar depression. Use of inpatient or emergency department mental health care
      is a more specific indicator of risk.

PMID- 29361849
TI  - Role of Complex Epigenetic Switching in Tumor Necrosis Factor-alpha Upregulation
      in the Prefrontal Cortex of Suicide Subjects.
AB  - OBJECTIVE: Proinflammatory cytokines have recently received considerable
      attention for their role in suicidal behavior; however, how the expression of
      cytokine genes is regulated is not clearly known. The authors examined underlying
      mechanisms of critical cytokine gene tumor necrosis factor-alpha (TNF-alpha)
      dysregulation in the brains of individuals who died by suicide. METHOD: TNF-alpha
      expression was examined in the dorsolateral prefrontal cortex of the postmortem
      brains of persons with and without major depressive disorder who died by suicide
      and of persons with major depressive disorder who died of causes other than
      suicide. The role of putative microRNAs targeting TNF-alpha and RNA-binding
      protein Hu antigen R (HuR) was tested with in vitro and in vivo approaches and by
      examining expression of transactivation response RNA binding protein (TRBP).
      Genetic influence on TNF-alpha expression was determined by expression
      quantitative trait loci analysis and by genotyping three single-nucleotide
      polymorphisms in the promoter region of the TNF-alpha gene. Promoter methylation
      of TNF-alpha was determined by using methylated DNA immunoprecipitation assay.
      Expression of miR-19a-3p and TNF-alpha was also determined in the peripheral
      blood mononuclear cells of 12 healthy control subjects and 12 currently depressed
      patients with severe suicidal ideation. RESULTS: TNF-alpha expression was
      significantly higher in the dorsolateral prefrontal cortex of individuals who
      died by suicide, regardless of psychiatric diagnosis. Its expression level was
      also increased in individuals with major depressive disorder who died by causes
      other than suicide. On the other hand, expression of miR-19a-3p was upregulated
      specifically in individuals who died by suicide. In a preliminary observation,
      similar upregulation of TNF-alpha and miR-19a-3p was observed in the peripheral
      blood mononuclear cells of depressed patients with suicidal ideation. Despite its
      ability to directly target TNF-alpha in vitro, miR-19a-3p showed no interaction
      with TNF-alpha in the dorsolateral prefrontal cortex. HuR potentially stabilized
      TNF-alpha transcript, presumably by sequestering its 3' untranslated region from
      miR-19a-3p-mediated inhibition. Furthermore, decreased TRBP expression supported
      abnormality in the interaction between miR-19a-3p and TNF-alpha. Additionally,
      TNF-alpha transcriptional upregulation was associated with promoter
      hypomethylation, whereas no genetic influence on altered TNF-alpha or miR-19a-3p
      expression was observed in individuals who died by suicide. CONCLUSIONS: The data
      in this study provide mechanistic insights into the dysregulation of the TNF
      alpha gene in the brains of individuals who died by suicide, which could
      potentially be involved in suicidal behavior.

PMID- 29361850
TI  - Early Intervention in Bipolar Disorder.
AB  - Bipolar disorder is a recurrent disorder that affects more than 1% of the world
      population and usually has its onset during youth. Its chronic course is
      associated with high rates of morbidity and mortality, making bipolar disorder
      one of the main causes of disability among young and working-age people. The
      implementation of early intervention strategies may help to change the outcome of
      the illness and avert potentially irreversible harm to patients with bipolar
      disorder, as early phases may be more responsive to treatment and may need less
      aggressive therapies. Early intervention in bipolar disorder is gaining momentum.
      Current evidence emerging from longitudinal studies indicates that parental early
      onset bipolar disorder is the most consistent risk factor for bipolar disorder.
      Longitudinal studies also indicate that a full-blown manic episode is often
      preceded by a variety of prodromal symptoms, particularly subsyndromal manic
      symptoms, therefore supporting the existence of an at-risk state in bipolar
      disorder that could be targeted through early intervention. There are also
      identifiable risk factors that influence the course of bipolar disorder, some of
      them potentially modifiable. Valid biomarkers or diagnosis tools to help
      clinicians identify individuals at high risk of conversion to bipolar disorder
      are still lacking, although there are some promising early results. Pending more
      solid evidence on the best treatment strategy in early phases of bipolar
      disorder, physicians should carefully weigh the risks and benefits of each
      intervention. Further studies will provide the evidence needed to finish shaping
      the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision
      Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and
      G.E. Partridge reviewed a number of patients with manic-depressive illness in
      search of a unifying endo-psychic conflict. They concluded that understanding
      either phase of illness was "elusive" and "tantalizing beyond reach." (Am J
      Psychiatry 1925: 81: 643-662 ).

PMID- 29361851
TI  - Is Osteogenic Differentiation of Human Nucleus Pulposus Cells a Possibility for
      Biological Spinal Fusion?
AB  - Objective The purpose of this study was to investigate whether a simple,
      biologically robust method for inducing calcification of degenerate
      intervertebral discs (IVD) could be developed to provide an alternative treatment
      for patients requiring spinal fusion. Design Nucleus pulposus (NP) cells isolated
      from 14 human IVDs were cultured in monolayer and exposed to osteogenic medium,
      1,25-dihydroxyvitamin D3 (VitD3), parathyroid hormone (PTH), and bone morphogenic
      proteins (BMPs) 2/7 to determine if they could become osteogenic. Similarly
      explant cultures of IVDs from 11 patients were cultured in osteogenic media with
      and without prior exposure to VitD3 and BMP-2. Osteogenic differentiation was
      assessed by alkaline phosphatase activity and areas of calcification identified
      by alizarin red or von Kossa staining. Expression of osteogenic genes during
      monolayer culture was determined using polymerase chain reaction and explant
      tissues assessed for BMP inhibitors. Human bone marrow-derived mesenchymal
      stromal cells (MSCs) were used for comparison. Results Standard osteogenic media
      was optimum for promoting mineralization by human NP cells in monolayer. Some
      osteogenic differentiation was observed with 10 nM VitD3, but none following
      application of PTH or BMPs. Regions of calcification were detected in 2 of the
      eleven IVD tissue explants, one cultured in osteogenic media and one with the
      addition of VitD3 and BMP-2. Conclusions Human NP cells can become osteogenic in
      monolayer and calcification of the extracellular matrix can also occur, although
      not consistently. Inhibitory factors within either the cells or the extracellular
      matrix may hinder osteogenesis, indicating that a robust biological fusion at
      this time requires further optimization.

PMID- 29361852
TI  - Open to Exploration? Association of Personality Factors With Complementary
      Therapy Use After Breast Cancer Treatment.
AB  - PURPOSE: Many cancer survivors seek complementary therapies (CTs) to improve
      their quality of life. While it is well-known that women who are younger, more
      highly educated, and have higher incomes are more likely to use CTs, individual
      differences such as personality factors have been largely unexplored as
      predictors of CT use. METHODS: In a secondary analysis of a larger study, 270
      women with stage I to III breast cancer completed self-report measures of
      demographic and illness-related information, personality variables, and use of
      several different types of CTs. A series of logistic regression models were used
      to explore whether demographic, illness-related, and personality variables
      predicted different types of CT use. RESULTS: Prior relationships between
      education and CT use were replicated. There were no significant relationships
      between illness-related variables and different types of CT use. Of the 5
      personality factors, only openness to experience was a significant predictor of
      multiple types of CT use. CONCLUSIONS: Openness to experience may represent an
      individual difference variable that predicts CT use among cancer survivors. CTs
      themselves may represent a form of intellectual curiosity and novelty seeking.
      Further studies are needed to replicate and examine the generalizability of the
      relationship between openness to experience and CT use in oncology populations.

PMID- 29361853
TI  - Advances in prodrug design for Parkinson's disease.
AB  - INTRODUCTION: Parkinson's Disease (PD) is a neurodegenerative disorder of the
      central nervous system (CNS) characterized by motor dysfunctions, such as
      bradykinesia, rigidity, neuropsychiatric symptoms, and others. The
      pharmacological treatment of the disease is only symptomatic since, to date,
      there is no treatment to stop or slow PD. Currently, L-Dopa (LD) remains the gold
      standard therapy even though it undergoes peripheral metabolism causing several
      side effects, such as nausea, vomiting and orthostatic hypotension. Areas
      covered: This review is focused on recent developments in strategies involving
      prodrugs to enhance DA and/or LD absorption, their chemical and enzymatic
      stabilities, and selective targeting to the central nervous system. Expert
      opinion: The prodrug strategy remains one of the most promising approaches to
      improve pharmaceutical, pharmacokinetic, and pharmacodynamic properties of
      hydrophilic compounds, such as anti-Parkinson drugs (DA and LD). Prodrugs
      developed in recent years have demonstrated good pharmacokinetic profiles,
      affording a sustained release of LD and reducing its plasma level fluctuations.
      The development of new prodrugs that may reach the BBB unaltered and with a good
      ADME (Absorption, Distribution, Metabolism, Elimination) profile and
      pharmacological efficacy represents an exciting challenge for medicinal chemists.

PMID- 29361854
TI  - Double-level isthmic spondylolisthesis treated with posterior lumbar interbody
      fusion with cage.
AB  - OBJECTIVE: Double-level isthmic spondylolisthesis in the lumbar spine is rare.
      The authors report on 21 cases of double-level isthmic spondylolisthesis treated
      by posterior lumbar interbody fusion (PLIF) with cage. PATIENTS AND METHODS:
      Between 2005 and 2015, twenty-one patients with double-level isthmic
      spondylolisthesis who underwent posterior lumbar interbody fusion (PLIF) with
      cage were reviewed retrospectively. The VAS (Visual Analogue Scale) and JOA
      (Japanese Orthopedic Association) score were used to evaluate preoperative and
      postoperative clinical outcomes. RESULTS: The back pain and sciatica decreased
      from 6.53 and 4.24 points preoperatively to 1.80 and 1.18 points on the VAS at
      final follow-up, respectively. The average JOA score improved from 13.4 +/- 3.2
      preoperative to 25.4 +/- 1.5 (range, 17-28) points postoperative. The average
      recovery rate was 76.9%. The good and excellent rate was 85.7% (18/21). The
      fusion rate was 95.2% (20/21). Changes in disc height, degree of listhesis, whole
      lumbar lordosis, and sacral inclination following surgery were also observed.
      CONCLUSIONS: Our results suggest that PLIF with cage appears to be an appropriate
      technique for the treatment of double-level isthmic spondylolisthesis.

PMID- 29361855
TI  - Green synthesis of silver nanoparticles using Artemisia turcomanica leaf extract
      and the study of anti-cancer effect and apoptosis induction on gastric cancer
      cell line (AGS).
AB  - The current study was aimed (1) to study the green synthesis of silver
      nanoparticles using Artemisia turcomanica leaf extract, (2) to investigate the
      induction of apoptosis by biologically synthesized silver nanoparticles in
      gastric cancer cell line (AGS) and (3) to compare their anti-cancer potential
      with commercial silver nanoparticles. The specification and morphology of the
      phytosynthesized AgNPs were evaluated using transmission electron microscopy
      (TEM), scanning electron microscopy (SEM), UV-visible spectroscopy, X-ray
      diffraction and Fourier transform infrared spectroscopy (FTIR). The nanoparticles
      synthesized were of an average size of 22 nm. The cytotoxicity of biological and
      commercial nanoparticles was investigated in gastric cancer cells (AGS) as well
      as normal fibroblast cells (L-929) by MTT assay. By increasing the concentration
      of phytosynthesized and commercial silver nanoparticles, a decrease was observed
      in the cell viability. Increased apoptosis was observed in the cells treated with
      biological silver nanoparticles compared to untreated cells (p < .001). Based on
      these findings, it was inferred that biologically synthesized silver
      nanoparticles induced apoptosis, and showed a cytotoxic and anti-cancer effect
      against gastric cancer cell lines in a dose- and time-dependent manner.
      Biologically synthesized nanoparticles may possess higher anti-cancer properties
      than commercial silver nanoparticles.

PMID- 29361856
TI  - Catheterization laboratory activations and time intervals for patients with pre
      hospital ECGs.
AB  - OBJECTIVE: The use of pre-hospital ECGs (PH-ECG) reduces time to reperfusion for
      patients with ST-segment elevation myocardial infarction (STEMI). The feasibility
      of reperfusion therapy within 60 minutes for hospitals with 24/7 PCI capability
      has been questioned, and current guidelines have set time targets to 90 minutes.
      Our primary objective was to investigate the proportion of false-positive
      catheterization laboratory activations by PH-ECG. Our secondary objective was to
      describe the time intervals from first medical contact to reperfusion and to
      establish the proportion of patients receiving reperfusion within 60 minutes.
      DESIGN: A retrospective cohort study among 4298 patients for whom a PH-ECG was
      transmitted to the investigating hospital, mainly due to chest pain, during 2013
      were included. RESULTS: Among patients with PH-ECGs, 139 (3.2%) patients had a
      STEMI. There were 115 pre-hospital catheterization laboratory activations among
      which 16% (95% confidence interval 10-23) were false-positive for STEMI. The
      median total time from emergency call to arterial puncture was 76 minutes. The
      target of PCI within 60 minutes was met in 83% of the cases. The time from EMS
      arrival to PH-ECG was 20 minutes for female patients and 13 minutes for male
      patients (p < .001), and only 16% had a PH-ECG within 10 minutes from Emergency
      Medical Service arrival. CONCLUSION: The rate of false-positive catheterization
      laboratory activations based on pre-hospital ECGs was low and the target of PCI
      within 60 minutes is achievable for a majority of patients. Efforts should be
      made to reduce the time from ambulance arrival to PH-ECG transmission, especially
      for female patients.

PMID- 29361857
TI  - In vitro fibroblast migration by sustained release of PDGF-BB loaded in chitosan
      nanoparticles incorporated in electrospun nanofibers for wound dressing
      applications.
AB  - Migration of fibroblasts into wound area is a critical phenomenon in wound
      healing process. We used an appropriate system to fabricate an electrospun
      bioactive scaffold with controlled release of PDGF-BB in order to induce
      migration of primary skin fibroblast cells. First of all, protein-loaded chitosan
      nanoparticles based on ionic gelation interaction between chitosan and sodium
      tripolyphosphate were prepared. Then polycaprolactone electrospun fibers
      containing chitosan nanoparticles or PDGF-BB-loaded chitosan nanoparticles were
      prepared. Cellular attachment and morphology of cells seeded on scaffolds with or
      without PDGF-BB were evaluated by using a fluorescence microscope and scanning
      electron microscopy. Cells were well-oriented 72 h after seeding on the scaffolds
      containing PDGF-BB. The mean aspect ratio of populations on scaffold containing
      PDGF-BB-loaded chitosan nanoparticles was significantly greater than those on the
      scaffold containing chitosan nanoparticles but no PDGF-BB. Furthermore, the Arp2
      gene, which is involved in cell protrusion formation, showed about three times
      more expression at mRNA level, in cells seeding on PDGF-BB-containing scaffold
      compared to cells seeding on scaffold containing only chitosan nanoparticles,
      using Real Time PCR test. Finally, under agarose migration assay results
      demonstrated that cells' chemotaxic behavior was more toward scaffold containing
      PDGF-BB compared to the PDGF-BB alone or FBS group. In addition, in terms of
      distance, the cell mass could grow faster, in response to scaffold containing
      PDGF-BB compared to FBS or PDGF-BB alone; however, the number of migrating cells
      might be the same or significantly higher in the latter groups.

PMID- 29361858
TI  - Determination of the renal concentration capacity following intravenous
      administration of dDAVP in healthy humans.
AB  - The synthetic AVP analogue 1-desamino-8-d-arginine-vasopressin (dDAVP) is used
      for treatment of polyuric disorders. Lack of commercially available assays limits
      the usefulness of dDAVP as a diagnostic tool in the assessment of renal
      concentrating capacity. We aimed to develop a specific radioimmunoassay (RIA) for
      determination of plasma dDAVP (pdDAVP) in order to investigate the relationship
      between pdDAVP levels and urine osmolality (Uosm). Further, we aimed to determine
      the onset, duration, and maximum concentrating capacity following intravenous
      (i.v.) bolus dDAVP injection. The dDAVP assay was based on a well-established RIA
      for measurements of AVP. Fourteen healthy subjects (aged 15-18 years)
      participated. Blood and urine samples were collected prior to and after i.v.
      bolus of 0.03 ug/kg dDAVP. Diuresis and Uosm was measured for nine hours
      following dDAVP administration. PdDAVP and Uosm were analyzed.We established a
      specific RIA for the measurement of pdDAVP. All subjects reached maximal pdDAVP
      concentration (Cmax) 30 minutes following infusion, and a rise in Uosm after 60
      minutes. Maximal Uosm varied between subjects, with no direct correlation to the
      achieved pdDAVP levels. We found no significant intra-individual variation
      between two dDAVP infusions and the effect was reproducible in terms of Cmax and
      maximal Uosm. We characterized the relationship between pdDAVP and Uosm after
      dDAVP bolus injection in healthy adolescents using our dDAVP assay. Maximal Uosm
      achieved correlated with the baseline Uosm levels and seemed unrelated to
      achieved pdDAVP levels. The urine concentrating response was maintained at least
      eight hours.

PMID- 29361859
TI  - Methods for certification in colonoscopy - a systematic review.
AB  - INTRODUCTION: Reliable, valid, and feasible assessment tools are essential to
      ensure competence in colonoscopy. This study aims to provide an overview of the
      existing assessment methods and the validity evidence that supports them.
      METHODS: A systematic search was conducted in October 2016. Pubmed, EMBASE, and
      PsycINFO were searched for studies evaluating assessment methods to ensure
      competency in colonoscopy. Outcome variables were described and evidence of
      validity was explored using a contemporary framework. RESULTS: Twenty-five
      observational studies were included in the systematic review. Most studies were
      based on small sample sizes. The studies were categorized after outcome measures
      into five groups: Clinical process related outcome metrics (n = 2), direct
      observational colonoscopy assessment (n = 8), simulator based metrics (n = 11),
      automatic computerized metrics (n = 2), and self-assessment (n = 1). Validity
      score varied among the studies and only five studies presented sufficient
      evidence to recommend the tool for clinical assessment. CONCLUSIONS: The
      objectives vary throughout the presented tools. Some tools are global tools where
      others focus on procedural technical skill assessment or even part-task skills.
      There is a tendency in the most recent studies towards more specific assessment
      of technical skills. The majority of assessment methods lack sufficient validity
      evidence.

PMID- 29361860
TI  - Adoption and correlates of the Dundee Ready Educational Environment Measure
      (DREEM) in the evaluation of undergraduate learning environments - a systematic
      review.
AB  - BACKGROUND: The Dundee Ready Educational Environment Measure (DREEM) was
      specifically designed to measure the undergraduate medical educational
      environment. This study seeks to review the adoption of DREEM internationally,
      and its association with different learning contexts and learner factors in order
      to better support our learners and facilitate future applications and research.
      METHOD: A systematic literature review was conducted on all articles that adopted
      and reported data using the DREEM from 1997 to April 2017. RESULTS: Overall, the
      majority of 106 included studies from over 30 countries were conducted in Asia
      and Europe (76.4% of studies) within medical, dental, and nursing programs (86.8%
      of studies). Seventy-nine out of 98 studies (80.6%) which reported DREEM scores
      observed a mean total DREEM score within the range of "more positive than
      negative" (101-150 out of maximum 200 points). Higher DREEM scores were
      associated with better past academic achievement, quality of life, resilience,
      positive attitudes towards course, mindfulness, preparedness for practice, less
      psychological distress, and greater peer support. CONCLUSIONS: Future studies may
      want to examine other correlates of DREEM such as coping styles, personality
      profiles, burnout level, and DREEM scores can be incorporated into reviews of
      learning environments to ascertain longitudinal changes following educational
      interventions.

PMID- 29361861
TI  - Twelve tips for teaching the informed consent conversation.
AB  - Obtaining informed consent has been traditionally viewed as a mundane task,
      learned on the job and often relegated to an inexperienced member of the
      healthcare team. In reality, the process of obtaining informed consent is
      complex, challenging, and warrants focused teaching, observation and feedback.
      There are few published standards for what should be included in a high-quality
      informed consent conversation, and little or no guidance regarding how to best
      teach the process of conducting this type of shared decision-making conversation.
      The following twelve tips provide a roadmap for teaching the essential components
      of how to obtain informed consent, including both content and communication
      skills, with a focus on common pitfalls for trainees, and strategies to address
      them.

PMID- 29361862
TI  - Poorly Differentiated Neuroendocrine Carcinoma of the Sigmoid Tract in Long
      Standing Ulcerative Colitis: Report of a Case and Review of the Literature.
AB  - A 37-year-old male with long-standing and extensive ulcerative pancolitis
      developed a rapidly lethal poorly differentiated neuroendocrine carcinoma (NEC)
      in the sigmoid colon. Prior biopsies obtained from multiple sites of the colon
      during endoscopic surveillance showed minimal inflammatory changes and no sign of
      dysplasia. Patients with inflammatory bowel disease (IBD) are at increased risk
      of colorectal malignancies, and adenocarcinoma is the most common type of
      colorectal neoplasm associated with ulcerative colitis and Crohn's disease, but
      other types of epithelial and nonepithelial tumors have also been described in
      IBD. NECs arising in the setting of ulcerative colitis are very rare and are
      reported as anecdotic findings. We describe the clinicopathological features of
      an IBD-related NEC and review the previously reported cases.

PMID- 29361863
TI  - Design and Development of a Technology Platform for DNA-Encoded Library
      Production and Affinity Selection.
AB  - DNA-encoded libraries (DELs) have emerged as an efficient and cost-effective drug
      discovery tool for the exploration and screening of very large chemical space
      using small-molecule collections of unprecedented size. Herein, we report an
      integrated automation and informatics system designed to enhance the quality,
      efficiency, and throughput of the production and affinity selection of these
      libraries. The platform is governed by software developed according to a database
      centric architecture to ensure data consistency, integrity, and availability.
      Through its versatile protocol management functionalities, this application
      captures the wide diversity of experimental processes involved with DEL
      technology, keeps track of working protocols in the database, and uses them to
      command robotic liquid handlers for the synthesis of libraries. This approach
      provides full traceability of building-blocks and DNA tags in each split-and-pool
      cycle. Affinity selection experiments and high-throughput sequencing reads are
      also captured in the database, and the results are automatically deconvoluted and
      visualized in customizable representations. Researchers can compare results of
      different experiments and use machine learning methods to discover patterns in
      data. As of this writing, the platform has been validated through the generation
      and affinity selection of various libraries, and it has become the cornerstone of
      the DEL production effort at Lilly.

PMID- 29361864
TI  - tagFinder: A Novel Tag Analysis Methodology That Enables Detection of Molecules
      from DNA-Encoded Chemical Libraries.
AB  - Available tools to analyze sequencing data coming from DNA-encoded chemical
      libraries (DELs) are often limited to in-house methods, which usually rely on
      strictly looking for the particular DEL structure used. Current methods do not
      take into account technological errors, such as library codification and
      sequencing errors, when detecting the sequences. The vast amount of data produced
      by next-generation sequencing of DEL screens is usually enough to extract the
      minimum information needed for compound identification. Here, we report a
      methodology to deconvolute encoding oligonucleotides, thus optimizing the
      sequencing power regardless of the library size, design complexity, or sequencing
      technology chosen. tagFinder is a highly flexible tool for fast tag detection and
      thorough DEL results characterization, which requires minimal hardware resources,
      scales linearly, and does not introduce any analytical error. The methodology can
      even deal with sequencing errors and PCR duplicates on single- or double-stranded
      DNA, enhancing the analytical detection and quantification of molecules and the
      informativeness of the entire process. Source code is available at
      https://github.com/jamigo/tagFinder .

PMID- 29361865
TI  - Sjogren's with distal renal tubular acidosis complicating pregnancy.

PMID- 29361866
TI  - Challenges of endometrial assessment after ablation in women with postmenopausal
      bleeding - A case series.

PMID- 29361867
TI  - Learning to parent from Google? Evaluation of available online health evidence
      for parents of preterm infants requiring neonatal intensive care.
AB  - The study aim was to identify and evaluate the reliability and quality of online
      resources for parents of preterm infants seeking health information about their
      infant using the DISCERN tool and Health on Net code. An Internet search (
      www.google.com ) was used to identify websites for parents of preterm infants on
      their infants' health and health issues. For each search, the top 100 "hits" were
      downloaded, yielding 1200 websites. After reviewing websites for exclusion
      criteria and duplicates, 197 websites remained and were analyzed. According to
      the DISCERN tool, the websites had a moderate reliability score (mean = 29.88,
      standard deviation = 4.88, range: 18-40), moderate treatment score (mean = 24.15,
      standard deviation = 5.79, range: 10-35), and moderate overall quality score
      (mean = 3.41, standard deviation = 0.89, range: 1-5). Only 24 (12.2%) websites
      had current Health on Net code approval and no other websites met full
      eligibility for certification. Overall, the reliability and quality of
      information available online to parents of preterm infants is lacking.

PMID- 29361868
TI  - Deterministic Lateral Displacement: The Next-Generation CAR T-Cell Processing?
AB  - Reliable cell recovery and expansion are fundamental to the successful scale-up
      of chimeric antigen receptor (CAR) T cells or any therapeutic cell-manufacturing
      process. Here, we extend our previous work in whole blood by manufacturing a
      highly parallel deterministic lateral displacement (DLD) device incorporating
      diamond microposts and moving into processing, for the first time, apheresis
      blood products. This study demonstrates key metrics of cell recovery (80%) and
      platelet depletion (87%), and it shows that DLD T-cell preparations have high
      conversion to the T-central memory phenotype and expand well in culture,
      resulting in twofold greater central memory cells compared to Ficoll-Hypaque
      (Ficoll) and direct magnetic approaches. In addition, all samples processed by
      DLD converted to a majority T-central memory phenotype and did so with less
      variation, in stark contrast to Ficoll and direct magnetic prepared samples,
      which had partial conversion among all donors (<50%). This initial comparison of
      T-cell function infers that cells prepared via DLD may have a desirable bias,
      generating significant potential benefits for downstream cell processing. DLD
      processing provides a path to develop a simple closed system that can be
      automated while simultaneously addressing multiple steps when there is potential
      for human error, microbial contamination, and other current technical challenges
      associated with the manufacture of therapeutic cells.

PMID- 29361869
TI  - Twelve tips for medical students to conduct a systematic review.
AB  - BACKGROUND: Medical students engaged in research develop general skills that are
      instrumental to clinical practice. The systematic review, a cornerstone of
      evidence-based medicine, represents an ideal starting point for student
      researchers. AIM AND METHODS: To outline twelve tips on conducting a systematic
      review for medical students with limited research experience. RESULTS: The tips
      in this article are practical, comprehensive, and informed by the authors
      experience as medical students. CONCLUSION: The twelve tips can help medical
      students contribute to the literature and build a valuable skillset for future
      research and clinical practice.

PMID- 29361870
TI  - Correction to: Potential autofertility in true hermaphrodites.

PMID- 29361871
TI  - Risk variation in celiac disease in a population from Southern Spain: evaluating
      the influence of the DQB1*02:02 allele frequency.
AB  - OBJECTIVES: To date, the greatest genetic risk factor known for celiac disease
      (CD) is the presence of HLA-DQ2 heterodimers, specifically DQ2.5 in state of
      homozygosis or heterozygosis. DQ2.2 variants are the second most important risk
      factor when carried trans to DQ2. This study aimed to determine the prevalence
      and risk genotypes of HLA-DR-DQ. MATERIAL AND METHODS: A total of 196 patients
      with CD and 206 healthy controls from the Province of Malaga (southern Spain)
      were included. The corresponding risk gradient in our population was established
      in accordance with the odds ratios (ORs) found. RESULTS: The heterozygous
      genotype for DR7-DQ2.2/DR3-DQ2.5 presented the highest risk (OR =6.404, p =
      .0001) followed by the DR3-DQ2.5 homozygous genotype (OR =4.721, p = .001). An
      intermediate risk was found for the DQ2.5 heterozygous genotype with no other DQ
      risk variant (DQ8 or DQ2.2). Similarly, these three genotypes had also an
      increase in the risk of associated-autoimmune diseases. The DQB1*02:01 allele was
      the most widely represented among patients with CD respect to the control group
      (f = 0.479, p = .0001), with the second most common being DQB1*02:02 (f = 0.209,
      p = .0001). CONCLUSIONS: In addition to the gene dosage effect confirmed in our
      report, and in contrast with previous studies, we found a raised risk for those
      patients with DQ2.2 heterodimers in trans configuration to DQ2.5 compared to
      DQ2.5 homozygous individuals. Therefore, in our population of patients with CD
      the frequency of DQ2.2 acts as a factor that increases the genetic risk of
      developing CD.

PMID- 29361872
TI  - Effectiveness of Basic Life Support Training for Middle School Students.
AB  - Bystander cardiopulmonary resuscitation improves survival after out-of-hospital
      cardiac arrest. This study aimed to assess the effectiveness of a basic life
      support (BLS) educational course given to 110 middle school children, using a
      pretest posttest design. In the pretest, students were asked to demonstrate BLS
      on a manikin to simulate a real-life scenario. After the pretest, a BLS training
      course of two sessions was provided, followed by posttest on the same manikin.
      Students were assessed using an observational sheet based on the American Heart
      Association's BLS guidelines. In the pretest, students showed significant
      weakness in the majority of guidelines. In the posttest, they demonstrated
      significant improvement in their BLS skills. BLS training in the middle school
      was effective, considering the lack of previous skills. It is recommended that
      BLS education be compulsory in the school setting.

PMID- 29361873
TI  - Potential Cognitive Benefits From Playing Music Among Cognitively Intact Older
      Adults: A Scoping Review.
AB  - The aging population is growing rapidly, raising rates of cognitive impairment,
      which makes strategies for protection against cognitive impairment increasingly
      important. There is little evidence indicating highly effective interventions
      preventing or slowing onset of cognitive impairment. Music playing influences
      brain and cognitive function, activating multiple brain areas and using cognitive
      and motor functions as well as multiple sensory systems, simultaneously. The
      purpose of this study was to review the current evidence related to playing a
      musical instrument being a potentially protective mechanism against cognitive
      decline among older adults. Using scoping review procedures, four databases were
      searched. Paired reviewers analyzed articles for content, design, and bias.
      Eleven studies met study criteria and were included in the review. All studies
      showed that music playing was correlated with positive outcomes on cognitive
      ability; more high-quality research is needed in this area to understand
      mechanisms behind potential cognitive protection of music.

PMID- 29361875
TI  - Complications in translabyrinthine surgery of vestibular schwannoma.
AB  - OBJECTIVE: To evaluate the risk of complications associated with tumor size and
      patient's age in translabyrinthine vestibular schwannoma surgery. METHODS: 700
      patients with vestibular schwannoma primarily underwent translabyrinthine surgery
      between 1988 and 2014. Pre- and postoperative data were collected in a database
      and incidence of the postoperative complications cerebrospinal fluid leakage,
      meningitis, intracranial hemorrhage (ICH), facial nerve function and mortality
      were assessed and related to the tumor size and patient's age and retrospectively
      evaluated. RESULTS: The tumor size significantly influenced the incidence of ICH
      and facial nerve dysfunction whereas age was correlated to facial nerve outcome.
      CONCLUSIONS: The translabyrinthine approach is a safe surgical procedure with
      relatively low risks of complications. The tumor size was significantly
      associated with a higher risk of ICH and facial nerve dysfunction whereas age
      only influenced the facial nerve outcome.

PMID- 29361876
TI  - Impact of Admission Imaging Findings on Neurological Outcomes in Acute Cervical
      Traumatic Spinal Cord Injury.
AB  - Variable and unpredictable spontaneous recovery can occur after acute cervical
      traumatic spinal cord injury (tSCI). Despite the critical clinical and
      interventional trial planning implications of this tSCI feature, baseline
      measures to predict neurologic recovery accurately are not well defined. In this
      study, we used data derived from 99 consecutive patients (78 male, 21 female)
      with acute cervical tSCIs to assess the sensitivity and specificity of various
      clinical and radiological factors in predicting recovery at one year after
      injury. Categorical magnetic resonance imaging parameters included maximum canal
      compromise (MCC), maximum spinal cord compression (MSCC), longitudinal length of
      intramedullary lesion (IML), Brain and Spinal Injury Center (BASIC) score, and a
      novel derived Combined Axial and Sagittal Score (CASS). Logistic regression
      analysis of the area under the receiver operating characteristic curve (AUC) was
      applied to assess the differential predictive value of individual imaging
      markers. Admission American Spinal Injury Association Impairment Scale (AIS)
      grade, presence of a spinal fracture, and central cord syndrome were predictive
      of AIS conversion at one year. Both BASIC and IML were stronger predictors of AIS
      conversion compared with MCC and MSCC (p = 0.0002 and p = 0.04). The BASIC score
      demonstrated the highest overall predictive value for AIS conversion at one year
      (AUC 0.94). We conclude that admission intrinsic cord signal findings are robust
      predictive surrogate markers of neurologic recovery after cervical tSCI. Direct
      comparison of imaging parameters in this cohort of patients indicates that the
      BASIC score is the single best acute predictor of the likelihood of AIS
      conversion.

PMID- 29361877
TI  - Pharmacological Review on Asiatic Acid and Its Derivatives: A Potential Compound.
AB  - Natural triterpenes represent a group of pharmacologically active and
      structurally diverse organic compounds. The focus on these phytochemicals has
      been enormous in the past few years, worldwide. Asiatic acid (AA), a naturally
      occurring pentacyclic triterpenoid, is found mainly in the traditional medicinal
      herb Centella asiatica. Triterpenoid saponins, which are the primary constituents
      of C. asiatica, are commonly believed to be responsible for their extensive
      therapeutic actions. Published research work has described the molecular
      mechanisms underlying the various biological activities of AA and its
      derivatives, which vary for each chronic disease. However, a compilation of the
      various pharmacological properties of AA has not yet been done. Herein, we
      describe in detail the pharmacological properties of AA and its derivatives that
      inhibit multiple pathways of intracellular signaling molecules and transcription
      factors that are involved in the various stages of chronic diseases. Furthermore,
      the pharmacological activities of AA were compared with two natural compounds:
      curcumin and resveratrol. This review summarizes the research on AA and its
      derivatives and helps to provide future directions in the area of drug
      development.

PMID- 29361879
TI  - Diet Quality and Physical Fighting Among Youth: A Cross-National Study.
AB  - The predictors of engaging in physical violence appear to be quite diverse,
      covering an array of social and psychological risk factors. The present study
      expands upon this literature by exploring the link between diet quality and
      physical fighting during early adolescence using cross-national data from the
      2005/2006 Health Behaviors of School Children (HBSC) survey. The results reveal
      that the rate of physical fighting was 40% higher among youths with lower quality
      diets, whereas the odds of frequent physical fighting were 68% higher, relative
      to youths with better diets. Ancillary analyses reveal that (a) the link between
      diet quality and physical fighting was significantly larger among females and (b)
      significant associations between diet quality and physical fighting were detected
      in 38 of the 40 countries examined. Strategies designed to improve diet quality
      among youth may have the added benefit of reducing the likelihood of physical
      fighting and its negative sequelae.

PMID- 29361878
TI  - Quality of endoscopic surveillance of Barrett's esophagus.
AB  - OBJECTIVES: The aim of this study was to evaluate adherence to Barrett's
      esophagus (BE) surveillance guidelines in Denmark. METHODS: The Danish Pathology
      Registry was used to identify 3692 patients. A total of 300 patients were
      included by drawing a simple random sample. Description of the BE segment, biopsy
      protocol, communication with the pathologist and planned follow-up endoscopy, was
      evaluated. RESULTS: Thirty-one patients were excluded due to missing reports and
      83 patients (28%) due to no endoscopic evidence of BE. Endoscopists suspected BE
      in 186 patients (62%) and these patients were included. Prague C&M classification
      was used in 34% of the endoscopy reports. The median number of biopsies was 4
      (interquartile range (IQR), 3-6). The BE segment was stratified by lengths of 1
      5, 6-10 and 11-15 cm and endoscopists obtained a sufficient number of biopsies in
      12, 8 and 0% of cases, respectively. 28% of endoscopists described the exact
      location of the biopsy site in the pathology requisition. Patients with
      nondysplastic BE had endoscopic surveillance performed after a median of 24
      months (IQR, 6-24). CONCLUSIONS: Adherence to the Danish guidelines was poor.
      This may be associated with insufficient quality of BE surveillance. Lack of
      endoscopic evidence of BE in the Danish Pathology Registry may have
      underestimated the incidence of adenocarcinoma in BE patients in previous
      studies.

PMID- 29361880
TI  - An overview of pharmacotherapy for bipolar I disorder.
AB  - INTRODUCTION: Bipolar I disorder (BD I) is complex with a chronic course that
      significantly impacts a sufferer's quality of life. As of right now, there are
      many available treatments that aim to rapidly treat manic or depressive episodes
      and stabilize mood. The purpose of this report is to provide an up-to-date
      comprehensive review of the available evidence-based trials of pharmacotherapy
      for the treatment of BD I. Areas covered: This paper reviews randomized active
      comparator-controlled or placebo-controlled trials evaluating the use of current
      pharmacotherapy in adults with BD I from phase III to clinical practice.
      Monotherapy and combination therapy for acute and long-term treatment were
      reviewed for this purpose. Expert opinion: There are many treatments available
      for BD mania; however, the depressive and stabilization phases of the illness
      remain a clinical challenge. Unfortunately, randomized controlled trials do not
      represent 'real world' patients, as their strict inclusion and exclusion criteria
      do not allow for different features sometimes present in patients to be
      considered. Research efforts must also focus on treating cognitive deficits,
      which adds to lower functional outcome. The authors believe that there is dire
      need for new, more targeted treatments in BD I, with a critical view of the side
      effects.

PMID- 29361881
TI  - Dimethyl Fumarate Attenuates Neuroinflammation and Neurobehavioral Deficits
      Induced by Experimental Traumatic Brain Injury.
AB  - Traumatic brain injury (TBI) is a serious neuropathology that causes secondary
      injury mechanisms, including dynamic interplay between ischemic, inflammatory,
      and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in
      pre-clinical models of neuroinflammation and toxic oxidative stress, so the aim
      of the present work was to evaluate the potential beneficial effects of dimethyl
      fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in
      a mouse model of TBI induced by controlled cortical impact (CCI). Mice were
      administered DMF orally at the doses of 1, 10, and 30 mg/kg 1 h and 4 h after
      CCI. We performed histological, molecular, and immunohistochemistry analysis on
      the traumatic penumbral areas of the brain 24 h after CCI. DMF treatment notably
      reduced histological damage and behavioral impairments, reducing
      neurodegeneration as evidenced by assessments of neuronal loss, Fluoro-Jade C,
      and TUNEL staining; also, treatment with DMF blocked the apoptosis process
      increasing B-cell lymphoma 2 (Bcl-2) expression in injured cortex. Further, DMF
      treatment up-regulated antioxidant Kelch-like ECH-associated protein 1/nuclear
      factor erythroid 2-related factor pathway, inducing activation of manganese
      superoxide dismutase and heme-oxygenase-1 and reducing 4-hydroxy-2-nonenal
      staining. Also, regulating the NF-kappaB pathway, DMF treatment decreased the
      severity of inflammation through a modulation of neuronal nitric oxide synthase,
      interleukin 1, tumor necrosis factor, cyclooxygenase 2, and myeloperoxidase
      activity, reducing ionized calcium-binding adapter molecule 1 and glial
      fibrillary acidic protein expression. Our results support the thesis that DMF may
      be an effective neuroprotectant after brain trauma and warrants further study.

PMID- 29361882
TI  - Awake craniotomy for assisting placement of auditory brainstem implant in NF2
      patients.
AB  - OBJECTIVES: Auditory brainstem implants (ABIs) may be the only opportunity for
      patients with NF2 to regain some sense of hearing sensation. However, only a very
      small number of individuals achieved open-set speech understanding and high
      sentence scores. Suboptimal placement of the ABI electrode array over the
      cochlear nucleus may be one of main factors for poor auditory performance. In the
      current study, we present a method of awake craniotomy to assist with ABI
      placement. METHODS: Awake surgery and hearing test via the retrosigmoid approach
      were performed for vestibular schwannoma resections and auditory brainstem
      implantations in four patients with NF2. Auditory outcomes and complications were
      assessed postoperatively. RESULTS: Three of 4 patients who underwent awake
      craniotomy during ABI surgery received reproducible auditory sensations
      intraoperatively. Satisfactory numbers of effective electrodes, threshold levels
      and distinct pitches were achieved in the wake-up hearing test. In addition,
      relatively few electrodes produced non-auditory percepts. There was no serious
      complication attributable to the ABI or awake craniotomy. CONCLUSIONS: It is safe
      and well tolerated for neurofibromatosis type 2 (NF2) patients using awake
      craniotomy during auditory brainstem implantation. This method can potentially
      improve the localization accuracy of the cochlear nucleus during surgery.

PMID- 29361883
TI  - Intensity of Care at the End of Life Among Older Adults in Korea.
AB  - AIM: To examine the intensity of care at the end of life among older adults in
      Korea and to identify the individual and institutional factors associated with
      care intensity. METHODS: This secondary data analysis included a sample of 6278
      decedents aged 65 years or older who were identified from the 2009 to 2010 Korean
      National Health Insurance Service-National Sample Cohort Claims data. We examined
      the medical care received by the cohort in the last 30 days of their lives.
      RESULTS: Overall, 36.5% of the sample received at least 1 intensive care
      procedure in the last 30 days of their lives; 26.3% of patients experienced
      intensive care unit admission, with an average stay of 7.45 days, 19.5% received
      mechanical ventilation, 12.3% received cardiopulmonary resuscitation, and 15.5%
      had a feeding tube placement. A statistical analysis using a multiple logistic
      regression model with random effects showed that younger age, higher household
      income, primary diagnoses of diseases (ischemic heart disease, infectious
      disease, chronic lung disease, or chronic heart disease), and characteristics of
      care setting (large hospitals and facilities located in metropolitan areas) were
      significantly associated with the likelihood of receiving high-intensity care at
      the end of life. CONCLUSION: A substantial number of older adults in Korea
      experienced high-intensity end-of-life care. Both individual and institutional
      factors were associated with the likelihood of receiving high-intensity care.
      Gaining an understanding of the intensity of care at the end of life and the
      impact of the determinants would advance efforts to improve quality of care at
      the end of life for older adults in Korea.

PMID- 29361884
TI  - Evaluation of dietary intake in children and college students with and without
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVES: To evaluate dietary intake among individuals with and without
      attention-deficit hyperactivity disorder (ADHD), to evaluate the likelihood that
      those with ADHD have inadequate intakes. METHODS: Children, 7-12 years old, with
      (n = 23) and without (n = 22) ADHD, and college students, 18-25 years old, with
      (n = 21) and without (n = 30) ADHD comprised the samples. Children's dietary
      intake was assessed by a registered dietitian using 24-hour recalls over 3 days.
      College students kept a detailed food record over three days. Dietary information
      for both groups was entered into the Nutrition Data Systems for Research
      database, and output was analyzed using SAS 9.4. Nutrient analyses included the
      Healthy Eating Index-2010, Micronutrient Index (as a measure of overall
      micronutrient intake), and individual amino acids necessary for
      neurotransmission. Logistic regression was used to model the association of
      nutrient intake with ADHD. Models were adjusted for age, sex, IQ (or GPA), and
      energy intake (or total protein intake) as appropriate. Significance was
      evaluated at P = 0.05, and using the Benjamini-Hochberg corrected P-value for
      multiple comparisons. RESULTS: No evidence existed for reduced nutrient intake
      among those with ADHD compared to controls in either age group. Across both
      groups, inadequate intakes of vitamin D and potassium were reported in 95% of
      participants. Children largely met nutrient intake guidelines, while college
      students failed to meet these guidelines for nine nutrients. In regards to amino
      acid intake in children, an increased likelihood of having ADHD was associated
      with higher consumption of aspartate, OR = 12.61 (P = 0.01) and glycine OR =
      11.60 (P = 0.05); and a reduced likelihood of ADHD with higher intakes of
      glutamate, OR = 0.34 (P = 0.03). Among young adults, none of the amino acids were
      significantly associated with ADHD, though glycine and tryptophan approached
      significance. DISCUSSION: Results fail to support the hypothesis that ADHD is
      driven solely by dietary micronutrient inadequacy. However, amino acids
      associated with neurotransmission, specifically those affecting glutamatergic
      neurotransmission, differed by ADHD status in children. Amino acids did not
      reliably vary among college students. Future larger scale studies are needed to
      further examine whether or not dietary intake of amino acids may be a modulating
      factor in ADHD.

PMID- 29361885
TI  - Lessons in Program Evaluation: The ACTV Batterer Program Study and Its Claims.
AB  - The "Evaluation of the Acceptance and Commitment Therapy (ACT) curriculum for
      domestic violence offenders" illustrates the methodological issues associated
      with interpreting program evaluations and applying them to policy. Despite the
      "preliminary" evidence, the authors promote ACTV as more effective in terms of
      recidivism compared with DU/CBT (cognitive-behavioral therapy) programming. A
      more critical consideration of the research, however, exposes further limitations
      that counter the initial speculations and interpretations of the study outcome.
      Consequently, the effectiveness of ACTV over the DU/CBT option remains in
      question and raises the need for a broader discourse on program effectiveness.

PMID- 29361886
TI  - Sequential occurrence of Graves' disease and immune thrombocytopenic purpura as
      manifestations of immune reconstitution inflammatory syndrome in an HIV-infected
      patient.
AB  - Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients after
      initiating antiretroviral therapy usually involves worsening manifestations of
      overt infectious disease. Here, we describe a sporadic case of a late-diagnosed
      HIV-positive man who developed Graves' disease as the first noninfectious IRIS
      followed by immune thrombocytopenic purpura as the second noninfectious IRIS.

PMID- 29361887
TI  - Assessment of HIV disclosure and sexual behavior among Black men who have sex
      with men following a randomized controlled intervention.
AB  - Disclosure is important in human immunodeficiency virus (HIV) transmission risk
      reduction. This randomized controlled intervention assessed changes in and
      predictors of disclosure and risky sexual behavior among Black men who have sex
      with men (BMSM) living with HIV in the U.S. BMSM were randomly assigned to either
      the disclosure intervention or attention control case management group.
      Predictors of three disclosure types (behavior, beliefs, intentions) and
      condomless anal intercourse (CAI) included disclosure consequences (rewards and
      costs), disclosure readiness, and safer sex readiness. Mixed-effect results
      showed no differences between the groups in any of the outcomes; although
      disclosure behavior increased over time. Relationships were found between
      readiness to change and CAI; disclosure consequences and different disclosure
      types; and disclosure behavior and receptive CAI. When working with BMSM living
      with HIV, practitioners and prevention specialists should consider the importance
      of disclosure pertaining to receptive CAI and factors that support overall
      disclosure and safer sex.

PMID- 29361888
TI  - Focused development of advanced practice nurse roles for specific patient groups
      in a Swiss university hospital
AB  - Background: To cover future health care needs of the population, new care models
      are necessary. The development of advanced nursing practice (ANP) offers the
      opportunity to meet these challenges with novel services. At the Inselspital,
      Bern University Hospital, ANP services and corresponding advanced practice nurse
      (APN) roles have been developed since 2011. Purpose: The aim is to develop
      innovative and evidence based ANP services to supplement health care for specific
      patient groups and their family members with the goal to improve safety and
      achieve better outcomes. Methods: Project-based ANP services are developed in
      close collaboration of clinical departments and the Nursing Development Unit
      (NDU) of the Directorate of Nursing. Structure, process and outcome data are
      collected for evaluation. Findings: Currently, five ANP services are established
      and running, eight more are in the developmental phase. Most services address the
      long term care of patients with chronic illnesses and their family members. Ten
      APNs work between 10 % and 80 %, three are leading an ANP-team. APNs work over 50
      % in direct clinical practice, primarily in counselling. An ANP network connects
      APNs and NDU, promoting synergy and exchange. Conclusions: The available
      resources often constitute a challenge for the development of ANP services. Vital
      for the long-term success are an adequate extent of the position, the support by
      department directorate, the conceptual framework that is implemented across the
      whole hospital, and the development within project structures.

PMID- 29361889
TI  - The Role and Molecular Mechanism of Long Nocoding RNA-MEG3 in the Pathogenesis of
      Preeclampsia.
AB  - A growing body of evidence suggests that the dysregulation of long noncoding RNA
      is increasingly linked to many human diseases. Maternally expressed gene 3 (
      MEG3) is one such gene thought to be affected. In the placenta of patients with
      preeclampsia, there is reduced expression of MEG3; however, its role and the
      mechanism involved are not clear. Therefore, we examined the expression of MEG3,
      epithelial-mesenchymal transition (EMT) markers (E-cadherin and N-cadherin), and
      TGF-beta/smad signaling pathway genes ( TGF-beta1, smad3, and smad7) in the
      placental tissues of 20 patients with preeclampsia and 20 healthy patients. We
      further observed the impact of MEG3 on the invasion and migration functions of
      human trophoblast cells and the effects on EMT and TGF-beta/smad signaling
      pathways in an Human trophoblast cell-8 (HTR-8)Vneo cell line. The expression of
      MEG3 was lower in tissues from patients with preeclampsia having an EMT decline,
      as well as a messenger RNA expression of smad7. The expression of TGF-beta1 and
      smad3 were higher in patients with preeclampsia. In HTR-8/SVneo cells with
      overexpressed MEG3, the invasion and migration functions were enhanced and
      accompanied by higher EMT and a significantly increased expression of smad7. Our
      data indicate that MEG3 is closely associated with the pathogenesis of
      preeclampsia and thus associated with changes in the EMT of placental trophoblast
      cells. These results indicate that MEG3 regulation of trophoblast cell EMT via
      the TGF-beta pathway inhibitor smad7 may be the molecular mechanism involved in
      the pathogenesis of preeclampsia.

PMID- 29361891
TI  - [Impact of an e-learning program regarding patients' harmful alcohol consumption
      on the knowledge, attitudes and perceived competencies of nurses from an acute
      care hospital: a pretest-posttest-study].
AB  - : Impact of an e-learning program regarding patients' harmful alcohol consumption
      on the knowledge, attitudes and perceived competencies of nurses from an acute
      care hospital: a pretest-posttest-study Abstract. BACKGROUND: Harmful alcohol
      consumption is associated with approximately 1600 deaths in Switzerland annually,
      and is the third-largest risk factor for various diseases worldwide. It has been
      shown that through early identification of problematic drinking behaviours along
      with preventive intervention, alcohol-related illnesses and mortality can be
      reduced. Therefore, nurses play a crucial role for patients with alcohol
      problems. However, the most common reasons for nurses not providing preventive
      intervention are a lack of knowledge, personal attitudes and uncertainty.
      Learning programs hold the potential for influencing these factors. AIM: The aim
      of this study was to assess the impact of an e-learning program regarding
      patients' harmful alcohol consumption on the knowledge, attitudes and perceived
      competencies of nurses in an acute care hospital. METHOD: A pretest-posttest
      study was conducted with 33 registered nurses prior to and upon completion of the
      e-learning program. Data was collected from December 2013 to March 2014 using a
      literature-based questionnaire. RESULTS: It was shown that knowledge and
      perceived competencies significantly improved from pre-test to post-test. No
      significant differences were measured with regard to the attitudes. CONCLUSIONS:
      The results suggest that the alcohol e-learning program could be used to enhance
      nurses' knowledge and perceived competencies, both of which are related to the
      reduction of uncertainty and improvement of confidence. To foster non-judgemental
      attitudes towards affected people, classroom courses are recommended in addition
      to the e-learning program and the implementation of directives.

PMID- 29361890
TI  - Modeling Neurodegenerative Microenvironment Using Cortical Organoids Derived from
      Human Stem Cells.
AB  - Alzheimer's disease (AD) is one of the most common neurodegenerative disorders
      and causes cognitive impairment and memory deficits of the patients. The
      mechanism of AD is not well known, due to lack of human brain models. Recently,
      mini-brain tissues called organoids have been derived from human induced
      pluripotent stem cells (hiPSCs) for modeling human brain development and
      neurological diseases. Thus, the objective of this research is to model and
      characterize neural degeneration microenvironment using three-dimensional (3D)
      forebrain cortical organoids derived from hiPSCs and study the response to the
      drug treatment. It is hypothesized that the 3D forebrain organoids derived from
      hiPSCs with AD-associated genetic background may partially recapitulate the
      extracellular microenvironment in neural degeneration. To test this hypothesis,
      AD-patient derived hiPSCs with presenilin-1 mutation were used for cortical
      organoid generation. AD-related inflammatory responses, matrix remodeling and the
      responses to DAPT, heparin (completes with heparan sulfate proteoglycans [HSPGs]
      to bind Abeta42), and heparinase (digests HSPGs) treatments were investigated.
      The results indicate that the cortical organoids derived from AD-associated
      hiPSCs exhibit a high level of Abeta42 comparing with healthy control. In
      addition, the AD-derived organoids result in an elevated gene expression of
      proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha,
      upregulate syndecan-3, and alter matrix remodeling protein expression. Our study
      demonstrates the capacity of hiPSC-derived organoids for modeling the changes of
      extracellular microenvironment and provides a potential approach for AD-related
      drug screening.

PMID- 29361892
TI  - Rehabilitation of patients with venous diseases of the lower limbs: State of the
      art.
AB  - BACKGROUND: To date, no document comprehensively focused on the complex issue of
      the rehabilitation of chronic venous diseases of the lower limbs. METHOD: This
      article overviews and summarizes current strategies concerning venous
      rehabilitation of lower limbs. RESULTS: Venous rehabilitation is based on four
      main strategies: (1) lifestyle adaptations and occupational therapies; (2)
      physical therapies; (3) adapted physical activities; (4) psychological and social
      support. Rehabilitative protocols must be tailored to the specific needs of each
      patient, depending on the severity of chronic venous disease and on the location
      and pattern of venous lesion(s), but also on age, motor deficits, co-morbidities
      and psychosocial conditions. CONCLUSIONS: Venous rehabilitation consists of non
      pharmacologic and non-surgical interventions aiming at prevention of venous
      disease progression and complications, reduction of symptoms and improvement of
      quality of life. Well-designed clinical trials are required to evaluate the
      efficacy of the described rehabilitative protocols in influencing the evolution
      of venous disorders.

PMID- 29361893
TI  - Discovery of novel antimicrobial peptides: A transcriptomic study of the sea
      anemone Cnidopus japonicus.
AB  - As essential conservative component of the innate immune systems of living
      organisms, antimicrobial peptides (AMPs) could complement pharmaceuticals that
      increasingly fail to combat various pathogens exhibiting increased resistance to
      microbial antibiotics. Among the properties of AMPs that suggest their potential
      as therapeutic agents, diverse peptides in the venoms of various predators
      demonstrate antimicrobial activity and kill a wide range of microorganisms. To
      identify potent AMPs, the study reported here involved a transcriptomic profiling
      of the tentacle secretion of the sea anemone Cnidopus japonicus. An in silico
      search algorithm designed to discover toxin-like proteins containing AMPs was
      developed based on the evaluation of the properties and structural peculiarities
      of amino acid sequences. The algorithm revealed new proteins of the anemone
      containing antimicrobial candidate sequences, and 10 AMPs verified using high
      throughput proteomics were synthesized. The antimicrobial activity of the
      candidate molecules was experimentally estimated against Gram-positive and 
      negative bacteria. Ultimately, three peptides exhibited antimicrobial activity
      against bacterial strains, which suggests that the method can be applied to
      reveal new AMPs in the venoms of other predators as well.

PMID- 29361894
TI  - The visualCMAT: A web-server to select and interpret correlated mutations/co
      evolving residues in protein families.
AB  - The visualCMAT web-server was designed to assist experimental research in the
      fields of protein/enzyme biochemistry, protein engineering, and drug discovery by
      providing an intuitive and easy-to-use interface to the analysis of correlated
      mutations/co-evolving residues. Sequence and structural information describing
      homologous proteins are used to predict correlated substitutions by the Mutual
      information-based CMAT approach, classify them into spatially close co-evolving
      pairs, which either form a direct physical contact or interact with the same
      ligand (e.g. a substrate or a crystallographic water molecule), and long-range
      correlations, annotate and rank binding sites on the protein surface by the
      presence of statistically significant co-evolving positions. The results of the
      visualCMAT are organized for a convenient visual analysis and can be downloaded
      to a local computer as a content-rich all-in-one PyMol session file with multiple
      layers of annotation corresponding to bioinformatic, statistical and structural
      analyses of the predicted co-evolution, or further studied online using the built
      in interactive analysis tools. The online interactivity is implemented in HTML5
      and therefore neither plugins nor Java are required. The visualCMAT web-server is
      integrated with the Mustguseal web-server capable of constructing large structure
      guided sequence alignments of protein families and superfamilies using all
      available information about their structures and sequences in public databases.
      The visualCMAT web-server can be used to understand the relationship between
      structure and function in proteins, implemented at selecting hotspots and
      compensatory mutations for rational design and directed evolution experiments to
      produce novel enzymes with improved properties, and employed at studying the
      mechanism of selective ligand's binding and allosteric communication between
      topologically independent sites in protein structures. The web-server is freely
      available at https://biokinet.belozersky.msu.ru/visualcmat and there are no login
      requirements.

PMID- 29361895
TI  - Identification of potential drug targets for treatment of refractory epilepsy
      using network pharmacology.
AB  - Epilepsy is the fourth most common neurological disease after migraine, stroke,
      and Alzheimer's disease. Approximately one-third of all epilepsy cases are
      refractory to the existing anticonvulsants. Thus, there is an unmet need for
      newer antiepileptic drugs (AEDs) to manage refractory epilepsy (RE). Discovery of
      novel AEDs for the treatment of RE further retards for want of potential
      pharmacological targets, unavailable due to unclear etiology of this disease. In
      this regard, network pharmacology as an area of bioinformatics is gaining
      popularity. It combines the methods of network biology and polypharmacology,
      which makes it a promising approach for finding new molecular targets. This work
      is aimed at discovering new pharmacological targets for the treatment of RE using
      network pharmacology methods. In the framework of our study, the genes associated
      with the development of RE were selected based on analysis of available data. The
      methods of network pharmacology were used to select 83 potential pharmacological
      targets linked to the selected genes. Then, 10 most promising targets were chosen
      based on analysis of published data. All selected target proteins participate in
      biological processes, which are considered to play a key role in the development
      of RE. For 9 of 10 selected targets, the potential associations with different
      kinds of epilepsy have been recently mentioned in the literature published, which
      gives additional evidence that the approach applied is rather promising.

PMID- 29361896
TI  - Patient complaints as a means to improve quality of hospital care. Results of a
      qualitative content analysis
AB  - Background: Many hospitals have defined procedures for a complaint management. A
      systematic analysis of patient complaints helps to identify similar complaints
      and patterns so that targeted improvement measures can be derived (Gallagher &
      Mazor, 2015). Aim: Our three-month, nurse-led practice development project aimed
      1) to identify complaints regarding communication issues, 2) to systemise and
      prioritise complaints regarding communication issues, and 3) to derive clinic
      specific recommendations for improvement. Method: We analysed 273 complaints of
      patients documented by the quality management (secondary data analysis). Using
      content analysis and applying the coding taxonomy for inpatient complaints by
      Reader, Gillespie and Roberts (2014), we distinguished communication-related
      complaints. By further inductive differentiation of these complaints, we
      identified patterns and prioritised fields of action. Results: We identified 186
      communication-related complaints divided into 16 subcategories. For each
      subcategory, improvement interventions were derived, discussed and prioritised.
      Conclusions: Thus, patient complaints provided an excellent opportunity for
      reflection and workplace learning for nurses. The analysis gave impulse to
      exemplify the subject "person-centered care" for nurses.

PMID- 29361897
TI  - Administration of the metabotropic glutamate receptor subtype 5 allosteric
      modulator GET 73 with alcohol: A translational study in rats and humans.
AB  - Preclinical work suggests that GET 73 (N-[4-(trifluoromethyl)benzyl]-4
      methoxybutyramide), a novel metabotropic glutamate receptor subtype 5 negative
      allosteric modulator, may represent a novel pharmacological treatment for alcohol
      use disorder. Two independent experiments evaluated the effect of acutely
      administered GET 73 (0, 30, and 100 mg/kg, intragastrically) on alcohol-induced
      hypolocomotion ( n=72) and sedation/hypnosis ( n=36) in rats. In healthy male
      volunteers ( n=14), an open-label, randomised, crossover study was conducted to
      compare adverse events and pharmacokinetic parameters, in two experiments in
      which 300 mg GET 73 was administered, with and without alcohol, once and thrice.
      In rats, when administered with alcohol-vehicle, 100 mg/kg, but not 30 mg/kg, GET
      73 reduced spontaneous locomotor activity. When administered with alcohol, no
      dose of GET 73 altered either alcohol-induced hypolocomotion or
      sedation/hypnosis. In humans, both single and thrice 300 mg GET 73 administration
      were well tolerated, in the presence and absence of alcohol, with no differences
      in adverse events. There were no significant differences in relative
      bioavailability between administering 300 mg GET 73 in the presence or absence of
      alcohol.

PMID- 29361898
TI  - How much basic science content do second-year medical students remember from
      their first year?
AB  - While most medical students generally perform well on examinations and pass their
      courses during the first year, we do not know how much basic science content they
      retain at the start of their second year and how that relates to minimal
      competency set by the faculty. In the fall of 2014, before starting their second
      year courses, 27 medical students volunteered to participate in a study of long
      term retention of the basic sciences by taking a "retention exam" after a delay
      of 5-11 months. The overall mean performance when the students initially answered
      the 60 multiple choice questions (MCQs) was 82.8% [standard deviation (SD) =
      7.4%], which fell to 50.1% (SD = 12.1%) on the retention exam. This gave a mean
      retention of 60.4% (SD = 12.8%) with the retention for individual students
      ranging from 37 to 81%. The majority of students (23/27; 85%) fell below the
      minimal level of competency to start their second year. Medical educators should
      be more aware of the significant amount of forgetting that occurs during training
      and make better use of instructional strategies that promote long-term learning
      such as retrieval practice, interleaving, and spacing.

PMID- 29361899
TI  - Interpersonal factors in the Pharmacokinetics and Pharmacodynamics of
      Voriconazole: Are CYP2C19 genotypes enough for us to make a clinical decision?
AB  - Invasive mycoses are serious infections with high mortality and increasing
      incidence. Voriconazole, an important drug to treat invasive mycosis, is
      metabolized mainly by the cytochrome P450 family 2-subfamily C member 19 enzyme
      (CYP2C19) and is affected by the genotypes of CYP2C19. In this article, we review
      studies on how genotypes affect the pharmacokinetics and pharmacodynamics of
      voriconazole, and attempted to determine a method to deciding on dosage
      adjustments based on genotypes. The pharmacokinetics of voriconazole are
      influenced by various inter and intrapersonal factors, and for certain
      populations, such as geriatric patients and pediatric patients, these influences
      must be considered. CYP2C19 genotype represents the main part of the
      interpersonal variability related to voriconazole blood concentrations. Thus,
      monitoring the concentration of voriconazole is needed in clinical scenarios to
      minimize the negative influences of inter and intrapersonal factors. Several
      studies provided evidence on the stable trough concentration range from 1-2 to 4
      6 mg/L, which were combined to consider the efficacy and toxicity. However, the
      therapeutic drug concentration needs to be narrowed down and evaluated by large
      scale clinical trials. Though there is insufficient evidence on the relationship
      between CYP2C19 genotypes and clinical outcomes, there is a great potential for
      the initial voriconazole dose selection guiding by the CYP2C19 genotype. Finally,
      voriconazole therapeutic drug monitoring is essential to provide patient-specific
      dosing recommendations, leading to more effective anti-fungal regimens to
      increase clinical efficacy and reduce adverse drug reactions.

PMID- 29361900
TI  - Foreword.

PMID- 29361901
TI  - Editorial: Contemporary Applications and Concerns with Nanotech Based Drug
      Delivery.

PMID- 29361902
TI  - C60-fullerenes as Drug Delivery Carriers for Anticancer Agents: Promises and
      Hurdles.
AB  - BACKGROUND: C60-fullerenes (CFs) constitute a carbon-allotropic family with cage
      like fused-ring structure, comprising of 20 hexagons and 12 pentagons. Since
      discovery in 1985, CFs attracted the scientists from various strata for unique
      properties like tensile strength, nanometeric size, symmetric nature, thermal and
      photo conductivity, chemical tailoring opportunities and drug loading
      capabilities. Surprisingly, CFs are also established to possess antiviral,
      neuroprotective, antiinflammatory, MRI contrast and antioxidant properties.
      Though extensively explored for chemical modifications and therapeutic benefits,
      CFs and derivatives also offer immense promises in drug delivery, especially to
      the cancerous cells. OBJECTIVE: The present review is an attempt to highlight the
      promises of CFs in drug delivery, esp. of anticancer agents. The review also
      analyzes the safety concerns of CF-based drug delivery and attempts to discuss
      the promises and challenges in the light of preclinical and clinical data.
      METHODS: The raw material (research/review articles) for the manuscript was
      collected from Pubmed, Google scholar and Scopus and the keywords used were
      fullerenes, nanotechnology, nanomedicine, functionalization, safety, drug
      delivery and biomedical applications. CONCLUSION: The drug release rate
      controlling behavior, higher drug loading, immuno-neutrality, substantial
      biocompatibility, capability to bypass mononuclear phagocytic system, long
      circulating nature and tissue extraction by virtue of enhanced permeability and
      retention effect are the major promises of these nanocarriers. On the other hand,
      the concerns like elimination from the biological system, anticipated tissue
      toxicity, stability of the final product, sterility issues and commercial
      viability pose challenges in proper utilization of CFs as ideal drug delivery
      carriers. However, a few commercial products based on CFs with human safety
      evidences provide a ray of hope.

PMID- 29361903
TI  - Editorial: CRISPR Medicine: From Bench to Bedside.

PMID- 29361904
TI  - Spherical: an iterative workflow for assembling metagenomic datasets.
AB  - BACKGROUND: The consensus emerging from the study of microbiomes is that they are
      far more complex than previously thought, requiring better assemblies and
      increasingly deeper sequencing. However, current metagenomic assembly techniques
      regularly fail to incorporate all, or even the majority in some cases, of the
      sequence information generated for many microbiomes, negating this effort. This
      can especially bias the information gathered and the perceived importance of the
      minor taxa in a microbiome. RESULTS: We propose a simple but effective approach,
      implemented in Python, to address this problem. Based on an iterative
      methodology, our workflow (called Spherical) carries out successive rounds of
      assemblies with the sequencing reads not yet utilised. This approach also allows
      the user to reduce the resources required for very large datasets, by assembling
      random subsets of the whole in a "divide and conquer" manner. CONCLUSIONS: We
      demonstrate the accuracy of Spherical using simulated data based on completely
      sequenced genomes and the effectiveness of the workflow at retrieving lost
      information for taxa in three published metagenomics studies of varying sizes.
      Our results show that Spherical increased the amount of reads utilized in the
      assembly by up to 109% compared to the base assembly. The additional contigs
      assembled by the Spherical workflow resulted in a significant (P < 0.05) changes
      in the predicted taxonomic profile of all datasets analysed. Spherical is
      implemented in Python 2.7 and freely available for use under the MIT license.
      Source code and documentation is hosted publically at:
      https://github.com/thh32/Spherical .

PMID- 29361905
TI  - Diversity of plant defense elicitor peptides within the Rosaceae.
AB  - BACKGROUND: Plant elicitor peptides (Peps) are endogenous molecules that induce
      and amplify the first line of inducible plant defense, known as pattern-triggered
      immunity, contributing to protect plants against attack by bacteria, fungi and
      herbivores. Pep topic application and transgenic expression have been found to
      enhance disease resistance in a small number of model plant-pathogen systems. The
      action of Peps relies on perception by specific receptors, so displaying a family
      specific activity. Recently, the presence and activity of Peps within the
      Rosaceae has been demonstrated. Here we characterized the population of Pep
      sequences within the economically important plant family of Rosaceae, with
      special emphasis on the Amygdaleae and Pyreae tribes, which include the most
      relevant edible species such as apple, pear and peach, and numerous ornamental
      and wild species (e.g. photinia, firethorn and hawthorn). RESULTS: The systematic
      experimental search for Pep and the corresponding precursor PROPEP sequences
      within 36 Amygdaleae and Pyreae species, and 100 cultivars had a highly
      homogeneous pattern, with two tribe-specific Pep types per plant, i.e. Pep1 and
      Pep2 (Amygdaleae) or Pep3 and Pep4 (Pyreae). Pep2 and Pep3 are highly conserved,
      reaching identity percentages similar to those of genes used in plant
      phylogenetic analyses, while Pep1 and Pep4 are somewhat more variable, with
      similar values to the corresponding PROPEPs. In contrast to Pep3 and Pep4, Pep1
      and Pep2 sequences of different species paralleled their phylogenetic
      relationships, and putative ancestor sequences were identified. The large amount
      of sequences allowed refining of a C-terminal consensus sequence that would
      support the protective activity of Pep1-4 in a Prunus spp. and Xanthomonas
      arboricola pv. pruni system. Moreover, tribe-specific consensus sequences were
      deduced at the center and C-terminal regions of Peps, which might explain the
      higher protection efficiencies described upon topic treatments with Peps from the
      same tribe. CONCLUSIONS: The present study substantially enhances the knowledge
      on Peps within the Amygdaleae and Pyreae species. It can be the basis to design
      and fine-tune new control tools against important plant pathogens affecting
      Prunus, Pyrus and Malus species.

PMID- 29361906
TI  - Genome-wide DNA Methylation analysis in response to salinity in the model plant
      caliph medic (Medicago truncatula).
AB  - BACKGROUND: DNA methylation has a potential role in controlling gene expression
      and may, therefore, contribute to salinity adaptation in plants. Caliph medic
      (Medicago truncatula) is a model legume of moderate salinity tolerance capacity;
      however, a base-resolution DNA methylome map is not yet available for this plant.
      RESULTS: In this report, a differential whole-genome bisulfite sequencing (WGBS)
      was carried out using DNA samples extracted from root tissues exposed to either
      control or saline conditions. Around 50 million differentially methylated sites
      (DMSs) were recognized, 7% of which were significantly (p < 0.05, FDR < 0.05)
      altered in response to salinity. This analysis showed that 77.0% of the contexts
      of DMSs were mCHH, while only 9.1% and 13.9% were mCHG and mCG, respectively. The
      average change in methylation level was increased in all sequence contexts,
      ranging from 3.8 to 10.2% due to salinity stress. However, collectively, the
      level of the DNA methylation in the gene body slightly decreased in response to
      salinity treatment. The global increase in DNA methylation due to salinity was
      confirmed by mass spectrometry analysis. Gene expression analysis using qPCR did
      not reveal a constant relationship between the level of mCG methylation and the
      transcription abundance of some genes of potential importance in salinity
      tolerance, such as the potassium channel KAT3, the vacuolar H+-pyrophosphatase (V
      PPase), and the AP2/ERF and bZIP transcription factors, implying the involvement
      of other epigenetic gene expression controllers. Computational functional
      prediction of the annotated genes that embrace DMSs revealed the presence of
      enzymes with potential cellular functions in biological processes associated with
      salinity tolerance mechanisms. CONCLUSIONS: The information obtained from this
      study illustrates the effect of salinity on DNA methylation and shows how plants
      can remodel the landscape of 5-methylcytosine nucleotide (5-mC) in the DNA across
      gene structures, in response to salinity. This remodeling varies between gene
      regions and between 5-mC sequence contexts. The mCG has a vague impact on the
      expression levels of a few selected potentially important genes in salt tolerant
      mechanisms.

PMID- 29361907
TI  - Genetical genomics of growth in a chicken model.
AB  - BACKGROUND: The genetics underlying body mass and growth are key to understanding
      a wide range of topics in biology, both evolutionary and developmental. Body mass
      and growth traits are affected by many genetic variants of small effect. This
      complicates genetic mapping of growth and body mass. Experimental intercrosses
      between individuals from divergent populations allows us to map naturally
      occurring genetic variants for selected traits, such as body mass by linkage
      mapping. By simultaneously measuring traits and intermediary molecular
      phenotypes, such as gene expression, one can use integrative genomics to search
      for potential causative genes. RESULTS: In this study, we use linkage mapping
      approach to map growth traits (N = 471) and liver gene expression (N = 130) in an
      advanced intercross of wild Red Junglefowl and domestic White Leghorn layer
      chickens. We find 16 loci for growth traits, and 1463 loci for liver gene
      expression, as measured by microarrays. Of these, the genes TRAK1, OSBPL8,
      YEATS4, CEP55, and PIP4K2B are identified as strong candidates for growth loci in
      the chicken. We also show a high degree of sex-specific gene-regulation, with
      almost every gene expression locus exhibiting sex-interactions. Finally, several
      trans-regulatory hotspots were found, one of which coincides with a major growth
      locus. CONCLUSIONS: These findings not only serve to identify several strong
      candidates affecting growth, but also show how sex-specificity and local gene
      regulation affect growth regulation in the chicken.

PMID- 29361908
TI  - Genetical genomics of quality related traits in potato tubers using proteomics.
AB  - BACKGROUND: Recent advances in ~omics technologies such as transcriptomics,
      metabolomics and proteomics along with genotypic profiling have permitted the
      genetic dissection of complex traits such as quality traits in non-model species.
      To get more insight into the genetic factors underlying variation in quality
      traits related to carbohydrate and starch metabolism and cold sweetening, we
      determined the protein content and composition in potato tubers using 2D-gel
      electrophoresis in a diploid potato mapping population. Upon analyzing we made
      sure that the proteins from the patatin family were excluded to ensure a better
      representation of the other proteins. RESULTS: We subsequently performed pQTL
      analyses for all other proteins with a sufficient representation in the
      population and established a relationship between proteins and 26 potato tuber
      quality traits (e.g. flesh colour, enzymatic discoloration) by co-localization on
      the genetic map and a direct correlation study of protein abundances and
      phenotypic traits. Over 1643 unique protein spots were detected in total over the
      two harvests. We were able to map pQTLs for over 300 different protein spots some
      of which co-localized with traits such as starch content and cold sweetening.
      pQTLs were observed on every chromosome although not evenly distributed over the
      chromosomes. The largest number of pQTLs was found for chromosome 8 and the
      lowest for chromosome number 10. For some 20 protein spots multiple QTLs were
      observed. CONCLUSIONS: From this analysis, hotspot areas for protein QTLs were
      identified on chromosomes three, five, eight and nine. The hotspot on chromosome
      3 coincided with a QTL previously identified for total protein content and had
      more than 23 pQTLs in the region from 70 to 80 cM. Some of the co-localizing
      protein spots associated with some of the most interesting tuber quality traits
      were identified, albeit far less than we had anticipated at the onset of the
      experiments.

PMID- 29361910
TI  - Assessment of cancers' diagnostic stage in a Deaf community - survey about 4363
      Deaf patients recorded in French units.
AB  - BACKGROUND: Deaf people represent 0.1% of the French population and their access
      to public health campaigns is limited due to their frequent illiteracy and the
      infrequent use of sign language in campaigns. There is also a lack of general
      health knowledge in spite of the existence of French Deaf Care Units (UASS). The
      aim of this study is to assess the average diagnostic stage of cancer in the Deaf
      Community and discuss deafness as a contributing factor. METHODS: Four thousand
      three hundred sixty-three Deaf patients recorded in five UASS, 80 diagnosed
      between 2005/01/01 and 2014/12/31 were selected from medical records and/or ICD
      10 coding. Data regarding cancers were extracted, grouped by stage and compared
      to literature. Statistical significance was tested with Fisher's Exact Test.
      RESULTS: Eighty patients were selected. Most cancers were diagnosed at advanced
      stages: of 11 prostate cancers, 46% were locally advanced and 18% were
      metastatic. (In the general population, this was respectively 3% and 10.4% (p <
      0.01)). Of six colorectal cancers, 67% were diagnosed at stage III and 33% at
      stage IV. (Respectively 20.6% and 26.6% (p = 0.03) in the general population). In
      contrast, of the 15 breast cancers, 93% were diagnosed at stages T1-T3 that was
      earlier than in the general population (p = 0.43). CONCLUSION: In this study, we
      observed a delay cancer diagnosis among Deaf people. Complicated and/or non
      systematic screening procedures for cancers would be involved. Which is most
      likely the result of many factors (communication, medical knowledge). Increasing
      UASS coverage and health information campaigns in sign language could assist in
      earlier cancer diagnosis.

PMID- 29361909
TI  - Three-dimensional spatial analysis of missense variants in RTEL1 identifies
      pathogenic variants in patients with Familial Interstitial Pneumonia.
AB  - BACKGROUND: Next-generation sequencing of individuals with genetic diseases often
      detects candidate rare variants in numerous genes, but determining which are
      causal remains challenging. We hypothesized that the spatial distribution of
      missense variants in protein structures contains information about function and
      pathogenicity that can help prioritize variants of unknown significance (VUS) and
      elucidate the structural mechanisms leading to disease. RESULTS: To illustrate
      this approach in a clinical application, we analyzed 13 candidate missense
      variants in regulator of telomere elongation helicase 1 (RTEL1) identified in
      patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and
      neutral RTEL1 variants from the literature and public databases. We then used
      homology modeling to construct a 3D structural model of RTEL1 and mapped known
      variants into this structure. We next developed a pathogenicity prediction
      algorithm based on proximity to known disease causing and neutral variants and
      evaluated its performance with leave-one-out cross-validation. We further
      validated our predictions with segregation analyses, telomere lengths, and
      mutagenesis data from the homologous XPD protein. Our algorithm for classifying
      RTEL1 VUS based on spatial proximity to pathogenic and neutral variation
      accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC =
      0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also
      significantly correlated with effects on ATPase activity (Pearson r = -0.65, p =
      0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified
      from sequencing of RTEL1 from patients predicted five out of six disease
      segregating VUS to be pathogenic. We provide structural hypotheses regarding how
      these mutations may disrupt RTEL1 ATPase and helicase function. CONCLUSIONS:
      Spatial analysis of missense variation accurately classified candidate VUS in
      RTEL1 and suggests how such variants cause disease. Incorporating spatial
      proximity analyses into other pathogenicity prediction tools may improve accuracy
      for other genes and genetic diseases.

PMID- 29361911
TI  - Shifting breast cancer surveillance from current hospital setting to a community
      based setting: a cost-effectiveness study.
AB  - BACKGROUND: This study explores the effectiveness and cost-effectiveness of
      surveillance after breast cancer treatment provided in a hospital-setting versus
      surveillance embedded in the community-based National Breast Cancer Screening
      Program (NBCSP). METHODS: Using a decision tree, strategies were compared on
      effectiveness and costs from a healthcare perspective over a 5-year time horizon.
      Women aged 50-75 without distant metastases that underwent breast conserving
      surgery in 2003-2006 were selected from the Netherlands Cancer Registry (n =
      14,093). Key input parameters were mammography sensitivity and specificity, risk
      of loco regional recurrence (LRR), and direct healthcare costs. Primary outcome
      measure was the proportion true test results (TTR), expressed as the positive and
      negative predictive value (PPV, NPV). The incremental cost-effectiveness ratio
      (ICER) is defined as incremental costs per TTR forgone. RESULTS: For the NBCSP
      strategy, 13,534 TTR (8 positive; 13,526 negative), and 12,923 TTR (387 positive;
      12,536 negative) were found for low and high risks respectively. For the hospital
      based strategy, 26,663 TTR (13 positive; 26,650 negative) and 24,883 TTR (440
      positive; 24,443 negative) were found for low and high risks respectively. For
      low risks, the PPV and NPV for the NBCSP-based strategy were 3.31% and 99.88%,
      and 2.74% and 99.95% for the hospital strategy respectively. For high risks, the
      PPV and NPV for the NBCSP-based strategy were 64.10% and 98.87%, and 50.98% and
      99.71% for the hospital-based strategy respectively. Total expected costs of the
      NBCSP-based strategy were lower than for the hospital-based strategy (low risk:
      ?1,271,666 NBCSP vs ?2,698,302 hospital; high risk: ?6,939,813 NBCSP vs
      ?7,450,150 hospital), rendering ICERs that indicate cost savings of ?109 (95%CI
      ?95-?127) (low risk) and ?43 (95%CI ?39-?56) (high risk) per TTR forgone.
      CONCLUSION: Despite expected cost-savings of over 50% in the NBCSP-based
      strategy, it is nearly 50% lower accurate than the hospital-based strategy,
      compromising the goal of early detection of LRR to an extent that is unlikely to
      be acceptable.

PMID- 29361912
TI  - What is it about a cancer diagnosis that would worry people? A population-based
      survey of adults in England.
AB  - BACKGROUND: Surveys indicate quite high prevalence of cancer worry in the general
      population, but little is known about what it is about cancer that worries
      people. A better understanding of the origins of cancer worry may help elucidate
      previously found inconsistencies in its behavioural effect on cancer prevention,
      screening uptake, and help-seeking for symptoms. In this study, we explore the
      prevalence and population distribution of general cancer worry and worries about
      specific aspects of cancer previously identified. METHODS: A population-based
      survey of 2048 English adults (18-70 years, April-May 2016), using face-to-face
      interviews to assess demographic characteristics, general cancer worry and twelve
      sources of cancer worry (adapted from an existing scale), including the
      emotional, physical, and social consequences of a diagnosis. RESULTS: In general,
      a third of respondents (37%) never worried about cancer, 57% worried
      occasionally/sometimes, and 6% often/very often. In terms of specific worries,
      two thirds would be 'quite a bit' or 'extremely' worried about the threat to life
      and emotional upset a diagnosis would cause. Half would worry about surgery,
      radiotherapy, chemotherapy, and loss of control over life. Worries about the
      social consequences were less commonly anticipated: just under half would worry
      about financial problems or their social roles, and a quarter would be worried
      about effects on identity, important relationships, gender role, and sexuality.
      Women and younger people reported more frequent worry about getting cancer, and
      would be more worried about the emotional, physical, and social consequences of a
      cancer diagnosis (p < .001). Those from ethnic minority backgrounds reported less
      frequent worry about getting cancer than their white counterparts, but would be
      equally worried about the emotional and physical impact of a cancer diagnosis,
      and worried more about the social consequences of a cancer diagnosis (p < .05).
      CONCLUSIONS: The majority of English adults worry at least occasionally about
      getting cancer, and would be most worried about the emotional and physical impact
      of a cancer diagnosis. Distinguishing between the various worries that cancer can
      evoke may help inform efforts to allay undue worries in those who are deterred by
      them from engaging with cancer prevention and early detection.

PMID- 29361913
TI  - RNA-seq analysis reveals alternative splicing under salt stress in cotton,
      Gossypium davidsonii.
AB  - BACKGROUND: Numerous studies have focused on the regulation of gene expression in
      response to salt stress at the transcriptional level; however, little is known
      about this process at the post-transcriptional level. RESULTS: Using a diploid D
      genome wild salinity-tolerant cotton species, Gossypium davidsonii, we analyzed
      alternative splicing (AS) of genes related to salt stress by comparing high
      throughput transcriptomes from salt-treated and well-watered roots and leaves. A
      total of 14,172 AS events were identified involving 6798 genes, of which intron
      retention (35.73%) was the most frequent, being detected in 3492 genes. Under
      salt stress, 1287 and 1228 differential alternative splicing (DAS) events were
      identified in roots and leaves, respectively. These DAS genes were associated
      with specific functional pathways, such as "responses to stress", "metabolic
      process" and "RNA splicing", implying that AS represents an important pathway of
      gene regulation in response to salt stress. Several salt response genes, such as
      pyrroline-5-carboxylate synthase (P5CS), K+ channel outward (KCO1), plasma
      membrane intrinsic protein (PIP) and WRKY33 which were involved in osmotic
      balance, ion homeostasis, water transportation and transcriptional regulation,
      respectively, were identified with differential alternative splicing under salt
      stress. Moreover, we revealed that 13 genes encoding Ser/Arg-rich (SR) proteins
      related to AS regulation were differentially alternatively spliced under salt
      stress. CONCLUSION: This study first provide a comprehensive view of AS in G.
      davidsonii, and highlight novel insights into the potential roles of AS in plant
      responses to salt stress.

PMID- 29361914
TI  - Testes-specific protease 50 (TSP50) promotes invasion and metastasis by inducing
      EMT in gastric cancer.
AB  - BACKGROUND: TSP50 (testes-specific protease 50) has been reported to be a
      candidate oncogene and is overexpressed in various cancers. Our previous study
      demonstrated that TSP50 protein is elevated in gastric cancer, and its high
      expression is associated with unfavorable prognosis and lymph node metastasis.
      However, the role of TSP50 in gastric cancer remains elusive. METHODS: qRT-PCR,
      western blot were used to determine TSP50 expression in gastric cancer cell
      lines. Role of TSP50 in proliferation and invasion was examined by BrdU
      incorporation assay, cell count, wound healing and transwell assay.
      Immunohistochemistry and western blot were performed to identify the potential
      mechanisms involved. RESULTS: TSP50 was highly expressed in most of the gastric
      cancer cell lines at both mRNA and protein levels. Up-regulation of TSP50 in
      gastric cancer cells enhanced proliferation and invasiveness, whereas down
      regulation of TSP50 by its specific shRNA decreased it. A negative correlation
      between TSP50 and E-Cadherin was found in gastric cancer tissues, and combination
      of them improves the prediction for prognosis and lymph node metastasis.
      Mechanistic studies revealed that overexpression of TSP50 increased the
      expression of epithelial-to-mesenchymal transition (EMT) markers including
      Vimentin, and Twist, and decreased the epithelial marker E-Cadherin. NF-kappaB
      signaling pathway is involved in the regulatory effects of TSP50 on EMT,
      migration and invasion in gastric cancer cells. CONCLUSION: TSP50 promotes the
      proliferation, migration and invasion of gastric cancer cells involving NF-kappaB
      dependent EMT activation. Targeting TSP50 may provide a novel therapeutic
      strategy for the management of gastric cancer.

PMID- 29361915
TI  - Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1
      antibody nivolumab: the first report.
AB  - BACKGROUND: Immune checkpoint blockade is developed as standard treatment for non
      small cell lung cancer. However immune-related adverse events (irAE) have still
      unknown complications. Here, we report a patient with lung squamous cell
      carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab.
      CASE PRESENTATION: A 75-year-old Japanese man with lung squamous cell carcinoma
      was administered nivolumab as second-line treatment. Two months after treatment
      with nivolumab, he presented acute paralysis in the bilateral lower limbs,
      sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions
      between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum
      disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other
      examinations. After treatment, steroid reactivity was poor. CONCLUSION: This is
      the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab
      induced irAE. Clinicians should be aware of this kind of potential neurological
      complication by using immune check point inhibitor and start the treatment of
      this irAE as soon as possible.

PMID- 29361916
TI  - Anxiety, depression and relationship satisfaction in the pregnancy following
      stillbirth and after the birth of a live-born baby: a prospective study.
AB  - BACKGROUND: Experiencing a stillbirth can be a potent stressor for psychological
      distress in the subsequent pregnancy and possibly after the subsequent birth. The
      impact on women's relationship with her partner in the subsequent pregnancy and
      postpartum remains uncertain. The objectives of the study were 1) To investigate
      the prevalence of anxiety and depression in the pregnancy following stillbirth
      and assess gestational age at stillbirth and inter-pregnancy interval as
      individual risk factors. 2) To assess the course of anxiety, depression and
      satisfaction with partner relationship up to 3 years after the birth of a live
      born baby following stillbirth. METHODS: This study is based on data from the
      Norwegian Mother and Child Cohort Study, a population-based pregnancy cohort. The
      sample included 901 pregnant women: 174 pregnant after a stillbirth, 362 pregnant
      after a live birth and 365 previously nulliparous. Anxiety and depression were
      assessed by short-form subscales of the Hopkins Symptoms Checklist, and
      relationship satisfaction was assessed by the Relationship Satisfaction Scale.
      These outcomes were measured in the third trimester of pregnancy and 6, 18 and 36
      months postpartum. Logistic regression models were applied to study the impact of
      previous stillbirth on depression and anxiety in the third trimester of the
      subsequent pregnancy and to investigate gestational age and inter-pregnancy
      interval as potential risk factors. RESULTS: Women pregnant after stillbirth had
      a higher prevalence of anxiety (22.5%) and depression (19.7%) compared with women
      with a previous live birth (adjusted odds ratio (aOR) 5.47, 95% confidence
      interval (CI) 2.90-10.32 and aOR 1.91, 95% CI 1.11-3.27) and previously
      nulliparous women (aOR 4.97, 95% CI 2.68-9.24 and aOR 1.91, 95% CI 1.08-3.36).
      Gestational age at stillbirth (> 30 weeks) and inter-pregnancy interval <  12
      months were not associated with depression and/or anxiety. Anxiety and depression
      decreased six to 18 months after the birth of a live-born baby, but increased
      again 36 months postpartum. Relationship satisfaction did not differ between
      groups. CONCLUSION: Women who have experienced stillbirth face a significantly
      greater risk of anxiety and depression in the subsequent pregnancy compared with
      women with a previous live birth and previously nulliparous women.

PMID- 29361917
TI  - Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to
      prognosis of non-small cell lung cancer.
AB  - BACKGROUND: Non-small cell lung cancer (NSCLC) remains the most common cause of
      cancer related death worldwide. Tumor-infiltrating macrophages are believed to
      play an important role in growth, progression, and metastasis of tumors. In
      NSCLC, the role of macrophages remains controversial; therefore, we aimed to
      evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma
      and to analyze their relations to patients' survival. METHODS: Lung tissue
      specimens from 80 NSCLC patients who underwent surgical resection for NSCLC
      (pathological stage I-III) and 16 control group subjects who underwent surgery
      because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical
      double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers
      for M2 macrophages) was performed and evaluated in a blinded manner. The numbers
      of M1 and M2 macrophages in tumor islets and stroma were counted manually.
      RESULTS: Predominant infiltration of M1 and M2 macrophages was observed in the
      tumor stroma compared with the tumor islets. M2 macrophages predominated over M1
      macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the
      number of total tumor-infiltrating M2 macrophages were independent predictors of
      patients survival: high infiltration of M1 macrophages in tumor islets was
      associated with increased overall survival in NSCLC (P < 0.05); high infiltration
      of total M2 macrophages in tumor (islets and stroma) was associated with reduced
      overall survival in NSCLC (P < 0.05). CONCLUSIONS: This study demonstrated that
      high infiltration of M1 macrophages in the tumor islets and low infiltration of
      total tumor-infiltrating M2 macrophages were associated with improved NSCLC
      patients' survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT01955343 ,
      registered on September 27, 2013.

PMID- 29361919
TI  - Factors related to subjective satisfaction following microendoscopic foraminotomy
      for cervical radiculopathy.
AB  - BACKGROUND: Microendoscopic foraminotomy has been reported to be effective for
      the treatment of cervical radiculopathy, using outcome measurement scores such as
      the neck disability index (NDI) and numerical rating scale (NRS). However, the
      scores for spine surgery do not always reflect the true subjective satisfaction
      of the patient. The purpose of this study was to evaluate factors related to
      subjective satisfaction following microendoscopic foraminotomy for cervical
      radiculopathy. METHODS: The subjects consisted of consecutive patients who
      underwent microendoscopic foraminotomy for cervical radiculopathy. Patient
      background information and operative data were collected. The NDI, the NRS score
      for the neck, upper back, and arm, and the EuroQOL-5D (EQ-5D) were assessed
      preoperatively and 1 year postoperatively. Postoperative subjective satisfaction
      was also assessed as a direct evaluation of satisfaction, and willingness to
      undergo the same operation if needed was assessed as an indirect evaluation.
      RESULTS: A total of 42 patients were included in this study. The mean age was
      52.9 +/- 11.8 years; 19.0% were female and 81.0% were male. The operation time
      for one level was 57.7 min and the estimated blood loss was minimal in most
      cases. All NDI, NRS, and EQ-5D scores improved significantly postoperatively.
      Univariate analyses revealed that the factors related to subjective satisfaction
      were younger age, non-smoking status, high preoperative NDI score, and low
      postoperative NRS score for the arm. Factors related to the willingness to
      undergo the same operation if needed were high preoperative NDI scores, high
      preoperative NRS scores for the arm, and low preoperative EQ-5D scores.
      CONCLUSIONS: Factors related to subjective satisfaction following microendoscopic
      foraminotomy include younger age, non-smoking status, high preoperative NDI
      score, high preoperative NRS score for the arm, low preoperative EQ-5D score, and
      a low postoperative NRS score for the arm.

PMID- 29361918
TI  - The identification of risk factors associated with patient and healthcare system
      delays in the treatment of tuberculosis in Tabriz, Iran.
AB  - BACKGROUND: Tuberculosis (TB) is a serious health concern, particularly in
      developing countries. Various delays, such as patient delay (PD) and healthcare
      system delay (HSD) in the TB process, are exacerbating the disease burden and
      increasing the rates of transmission and mortality in various global communities.
      Therefore, the aim of this study is to identify risk factors associated with PD
      and HSD in TB patients in Tabriz, Iran. METHODS: A cross-sectional study was
      conducted on 173 TB patients in Tabriz, Iran from 2012 to 2014. Patients were
      interviewed with a semi-structured questionnaire. Frequencies and percentages
      were reported for patient categories of sex, age, and education. The median and
      interquartile range (IQR) were reported for the time intervals of delays.
      Univariate and multivariate logistic regressions of delay in respect to socio
      demographic and clinical variables were performed. Statistical significance was
      set at p < 0.05. RESULTS: The median values for delays were 53 days for HSD (IQR
      = 73) and 13 days for PD (IQR = 57). Odds ratios (OR) associated with PD were:
      employed vs. unemployed (OR = 5.86, 95% CI: 1.59 to 21.64); public hospitals vs.
      private hospitals (OR = 2.64, 95% CI: 1.01 to 6.85); >= 3 vs. < 3 visits to
      health facilities before correct diagnosis (OR = 2.35, 95% CI: 1.08 to 5.11); and
      male vs. female (OR = 2.28, 95% CI: 1.29 to 4.39). The OR associated with HSD
      were: >= 3 vs. < 3 visits to health facilities before correct diagnosis (OR =
      9.44, 95% CI: 4.50 to 19.82), without vs. with access to TB diagnostic services
      (OR = 3.56, 95% CI: 1.85 to 6.83), and misdiagnosis as cold or viral infection
      vs. not (OR = 2.62, 95% CI: 1.40 to 4.91). CONCLUSIONS: The results provide for
      an important understanding of the risk factors associated with PD and HSD. One of
      the major recommendations is to provide more TB diagnostic knowledge and tools to
      primary health providers and correct diagnoses for patients during their initial
      visit to the health care facilities. The knowledge generated from this study will
      be helpful for prioritizing and developing strategies for minimizing delays,
      initiating early treatment to TB patients, and improving TB-related training
      programs and healthcare systems in Tabriz, Iran.

PMID- 29361920
TI  - Detecting functional change in response to exercise in knee osteoarthritis: a
      comparison of two computerized adaptive tests.
AB  - BACKGROUND: The intent of this study was to examine and compare the ability to
      detect change of two patient reported outcome (PRO) instruments that use a
      computerized adaptive test (CAT) approach to measurement. The Patient Reported
      Outcomes Measurement Information System (PROMIS(r)) Physical Function scale is a
      generic PRO, while the Osteoarthritis Computerized Adaptive Test (OA-CAT) is an
      osteoarthritis-specific PRO. METHODS: This descriptive, longitudinal study was
      conducted in a community setting, involving individuals from the greater Boston
      area. INCLUSION CRITERIA: age > 50, self-reported doctor-diagnosed knee
      osteoarthritis (OA) and knee pain. The PROMIS(r) Physical Function CAT and OA-CAT
      Functional Difficulty scale were administered at baseline and at the conclusion
      of a 6-week exercise program. Effect sizes (ES) were calculated for both
      measures, and bootstrap methods were used to construct confidence intervals and
      to test for significant ES differences between the measures. RESULTS: The OA-CAT
      Functional Difficulty scale achieved an ES of 0.62 (0.43, 0.87) compared to the
      PROMIS(r) Physical Function CAT ES of 0.42 (0.24, 0.63). ES estimates for the two
      CAT measures were not statistically different. CONCLUSIONS: The condition
      specific OA-CAT and generic PROMIS(r) Physical Function CAT both demonstrated the
      ability to detect change in function. While the OA-CAT scale showed larger effect
      size, no statistically significant difference was found in the effect size
      estimates for the generic and condition-specific CATs. Both CATs have potential
      for use in arthritis research. TRIAL REGISTRATION: This trial is registered with
      ClinicalTrials.gov on 6/21/11 (Identifier NCT01394874 ).

PMID- 29361921
TI  - "Happy feet": evaluating the benefits of a 100-day 10,000 step challenge on
      mental health and wellbeing.
AB  - BACKGROUND: An increased awareness of the health benefits of walking has emerged
      with the development and refinement of accelerometer equipment. Evidence is
      beginning to highlight the value of promoting walking, particularly focusing on
      the Japanese mark of obtaining 10,000 steps per day. Workplace based step
      challenges have become popular to engage large cohorts in increasing their daily
      physical activity in a sustainable and enjoyable way. Findings are now
      highlighting the positive health effects of these medium-term programs (typically
      conducted over a few months) in terms of cardiovascular health, reducing diabetes
      risk and improving lifestyle factors such as weight and blood pressure. As yet,
      research has not focused on whether similar improvements in psychological health
      and wellbeing are present. METHODS: This study investigated the impact of a 100
      day, 10,000 step program on signs of depression, anxiety and stress as well as
      general wellbeing using standardised psychological scales. RESULTS: The results
      indicated a small but consistent effect on all of these measures of mental health
      over the term of the program. This effect appeared irrespective of whether a
      person reached the 10,000 step mark. CONCLUSIONS: These results highlight
      improved mental health and wellbeing in people undertaking this 100-day 10,000
      step program and indicates the efficacy and potential of these programs for a
      modest, yet important improvement in mental health. Notably, targets reached may
      be less important than participation itself.

PMID- 29361922
TI  - Access to public drinking water fountains in Berkeley, California: a geospatial
      analysis.
AB  - BACKGROUND: In January 2015, Berkeley, California became the first city in the
      Unites States to impose a tax on sugar-sweetened beverages. The tax is intended
      to discourage purchase of sugary beverages and promote consumption of healthier
      alternatives such as tap water. The goal of the study was to assess the condition
      of public drinking water fountains and determine if there is a difference in
      access to clean, functioning fountains based on race or socio-economic status.
      METHODS: A mobile-GIS App was created to locate and collect data on existing
      drinking water fountains in Berkeley, CA. Demographic variables related to race
      and socio-economic status (SES) were acquired from the US Census - American
      Community Survey database. Disparities in access to, or condition of drinking
      water fountains relative to demographics was explored using spatial analyses.
      Spatial statistical-analysis was performed to estimate demographic
      characteristics of communities near the water fountains and logistic regression
      was used to examine the relationship between household median income or race and
      condition of fountain. RESULTS: Although most fountains were classified as
      functioning, some were dirty, clogged, or both dirty and clogged. No spatial
      relationships between demographic characteristics and fountain conditions were
      observed. DISCUSSION: All geo-located data and a series of maps were provided to
      the City of Berkeley and the public. CONCLUSIONS: The geo-database created as an
      outcome of this study is useful for prioritizing maintenance of existing
      fountains and planning the locations of future fountains. The methodologies used
      for this study could be applied to a wide variety of asset inventory and
      assessment projects such as clinics or pharmaceutical dispensaries, both in
      developed and developing countries.

PMID- 29361923
TI  - Percutaneous therapy of a mediastinal lymphangioma with fibrin glue: case report
      with clinical success after 4 years.
AB  - BACKGROUND: Lymphangioma of the mediastinum is a rare benign tumor, and most of
      the cases are treated by a surgical approach. CASE PRESENTATION: This work
      reports the case of a 62-year-old female with a large lymphangioma extending from
      her neck to her abdomen with dysphagia, dyspnea, and cough for 2 months. Because
      of the location of the mass, only bilateral excision could remove the
      multiloculated cyst completely. However, the patient's overall physical condition
      was very poor, and we thought she could not tolerate the bilateral surgery.
      Therefore, the patient was treated by percutaneous aspiration drainage followed
      by fibrin glue injection. Our method has never been reported in the treatment of
      such a large intrathoracic lesion thus far. CONCLUSIONS: Percutaneous puncture
      and aspiration drainage followed by fibrin glue injection may be a feasible
      treatment option for the therapy of intrathoracic lymphangioma, with less damage
      than with other therapies.

PMID- 29361924
TI  - Healthy offshore workforce? A qualitative study on offshore wind employees'
      occupational strain, health, and coping.
AB  - BACKGROUND: Offshore work has been described as demanding and stressful. Despite
      this, evidence regarding the occupational strain, health, and coping behaviors of
      workers in the growing offshore wind industry in Germany is still limited. The
      purpose of our study was to explore offshore wind employees' perceptions of
      occupational strain and health, and to investigate their strategies for dealing
      with the demands of offshore work. METHODS: We conducted 21 semi-structured
      telephone interviews with employees in the German offshore wind industry. The
      interviews were transcribed and analyzed in a deductive-inductive approach
      following Mayring's qualitative content analysis. RESULTS: Workers generally
      reported good mental and physical health. However, they also stated perceptions
      of stress at work, fatigue, difficulties detaching from work, and sleeping
      problems, all to varying extents. In addition, physical health impairment in
      relation to offshore work, e.g. musculoskeletal and gastrointestinal complaints,
      was documented. Employees described different strategies for coping with their
      job demands. The strategies comprised of both problem and emotion-focused
      approaches, and were classified as either work-related, health-related, or
      related to seeking social support. CONCLUSIONS: Our study is the first to
      investigate the occupational strain, health, and coping of workers in the
      expanding German offshore wind industry. The results offer new insights that can
      be utilized for future research in this field. In terms of practical
      implications, the findings suggest that measures should be carried out aimed at
      reducing occupational strain and health impairment among offshore wind workers.
      In addition, interventions should be initiated that foster offshore wind workers'
      health and empower them to further expand on effective coping strategies at their
      workplace.

PMID- 29361925
TI  - Long-term progression-free survival in an advanced lung adenocarcinoma patient
      harboring EZR-ROS1 rearrangement: a case report.
AB  - BACKGROUND: Crizotinib is recommended as first-line therapy in ROS1-driven lung
      adenocarcinoma. However, the optimal first-line therapy for this subgroup of lung
      cancer is controversial according to the available clinical data. CASE
      PRESENTATION: Here, we describe a 57-year-old man who was diagnosed with stage
      IIIB lung adenocarcinoma and EGFR/KRAS/ALK-negative tumors. The patient received
      six cycles of pemetrexed plus cisplatin as first-line therapy and then pemetrexed
      as maintenance treatment, with a progression-free survival (PFS) of 42 months.
      The patient relapsed and underwent re-biopsy. EZR-ROS1 fusion mutation was
      detected by next-generation sequencing (NGS). The patient was prescribed
      crizotinib as second-line therapy and achieved a PFS of 6 months. After disease
      progression, lorlatinib was administered as third-line therapy, with a favorable
      response. CONCLUSIONS: Prolonged PFS in patients receiving pemetrexed
      chemotherapy might be related to the EZR-ROS1 fusion mutation. Lorlatinib is an
      optimal choice in patients showing crizotinib resistance.

PMID- 29361926
TI  - Exploring the care provided to mothers and children by community health workers
      in South Africa: missed opportunities to provide comprehensive care.
AB  - BACKGROUND: Community health workers (CHWs) provide maternal and child health
      services to communities in many low and middle-income countries, including South
      Africa (SA). CHWs can improve access to important health interventions for
      isolated and vulnerable communities. In this study we explored the performance of
      CHWs providing maternal and child health services at household level and the
      quality of the CHW-mother interaction. METHODS: A qualitative study design was
      employed using observations and in-depth interviews to explore the content of
      household interactions, and experiences and perceptions of mothers and CHWs.
      Fifteen CHWs and 30 mothers/pregnant women were purposively selected in three
      rural districts of KwaZulu-Natal, SA. CHW household visits to mothers were
      observed and field notes taken, followed by in-depth interviews with mothers and
      CHWs. Observations and interviews were audio-recorded. We performed thematic
      analysis on transcribed discussions, and content analysis on observational data.
      RESULTS: CHWs provided appropriate and correct health information but there were
      important gaps in the content provided. Mothers expressed satisfaction with CHW
      visits and appreciation that CHWs understood their life experiences and therefore
      provided advice and support that was relevant and accessible. CHWs expressed
      concern that they did not have the knowledge required to undertake all activities
      in the household, and requested training and support from supervisors during
      household visits. CONCLUSIONS: Key building blocks for a successful CHW programme
      are in place to provide services for mothers and children in households but
      further training and supervision is required if the gaps in CHW knowledge and
      skills are to be filled.

PMID- 29361927
TI  - Incidence of endophthalmitis after 23-gauge pars plana vitrectomy.
AB  - BACKGROUND: Endophthalmitis is a rare but severe complication following PPV. The
      incidence of endophthalmitis varies between 20-gauge, 23-gauge, and 25-gauge
      incisions. The incidence and clinical features of endophthalmitis after 23-gauge
      PPV in an eye hospital in China was reported in this study. METHODS: Data of the
      eyes that underwent 23-gauge PPV from January 2011 to December 2014 at the Eye
      Hospital of Wenzhou Medical University was retrospectively collected. All the
      information was obtained from the electronic medical system. The exclusion
      criteria included: (1) preoperative diagnosis of endophthalmitis; (2) history of
      vitrectomy; (3) intraocular surgery within 6 months; (4) history of ocular
      penetrating trauma; (5) sutures for any of the 3 sclerotomy incisions; (6)
      patients with cancer, acquired immune deficiency syndrome, or taking drugs that
      may influence the immune system. The diagnosis of endophthalmitis was based on
      clinical characteristics and/or culture results from an operative sample.
      RESULTS: Three thousand nine hundred seventy nine eyes that underwent 23-gauge
      PPV surgery were included in this study. Among these eyes, 3 eyes developed
      endophthalmitis after surgery, giving an incidence of 0.075% (3/3979). The period
      in which endophthalmitis developed ranged from 1 to 5 days post-operation. The
      visual acuity decreased to hand motions or light perception postoperatively. The
      culture of aqueous and vitreous of the 2 eyes revealed Staphylococcus epidermidis
      and enterococcus faecalis respectively, however was negative for the third eye.
      All 3 eyes had a favorable response to the treatment of vitreous tap and
      intravitreal antibiotics injection. Two eyes gained visual acuity of 0.05 and
      0.5, respectively at the final visit. CONCLUSIONS: Endophthalmitis is a rare but
      sight-threatening complication after 23-gauge pars plana vitrectomy. The peak
      duration of onset was within 5 days post-operation, with gram positive cocci
      being the common pathogenic organism.

PMID- 29361928
TI  - Shrinkage Clustering: a fast and size-constrained clustering algorithm for
      biomedical applications.
AB  - BACKGROUND: Many common clustering algorithms require a two-step process that
      limits their efficiency. The algorithms need to be performed repetitively and
      need to be implemented together with a model selection criterion. These two steps
      are needed in order to determine both the number of clusters present in the data
      and the corresponding cluster memberships. As biomedical datasets increase in
      size and prevalence, there is a growing need for new methods that are more
      convenient to implement and are more computationally efficient. In addition, it
      is often essential to obtain clusters of sufficient sample size to make the
      clustering result meaningful and interpretable for subsequent analysis. RESULTS:
      We introduce Shrinkage Clustering, a novel clustering algorithm based on matrix
      factorization that simultaneously finds the optimal number of clusters while
      partitioning the data. We report its performances across multiple simulated and
      actual datasets, and demonstrate its strength in accuracy and speed applied to
      subtyping cancer and brain tissues. In addition, the algorithm offers a
      straightforward solution to clustering with cluster size constraints.
      CONCLUSIONS: Given its ease of implementation, computing efficiency and
      extensible structure, Shrinkage Clustering can be applied broadly to solve
      biomedical clustering tasks especially when dealing with large datasets.

PMID- 29361929
TI  - Interpreting population reach of a large, successful physical activity trial
      delivered through primary care.
AB  - BACKGROUND: Failure to include socio-economically deprived or ethnic minority
      groups in physical activity (PA) trials may limit representativeness and could
      lead to implementation of interventions that then increase health inequalities.
      Randomised intervention trials often have low recruitment rates and rarely assess
      recruitment bias. A previous trial by the same team using similar methods
      recruited 30% of the eligible population but was in an affluent setting with few
      non-white residents and was limited to those over 60 years of age. METHODS: PACE
      UP is a large, effective, population-based walking trial in inactive 45-75 year
      olds that recruited through seven London general practices. Anonymised practice
      demographic data were available for all those invited, enabling investigation of
      inequalities in trial recruitment. Non-participants were invited to complete a
      questionnaire. RESULTS: From 10,927 postal invitations, 1150 (10.5%) completed
      baseline assessment. Participation rate ratios (95% CI), adjusted for age and
      gender as appropriate, were lower in men 0.59 (0.52, 0.67) than women, in those
      under 55 compared with those >=65, 0.60 (0.51, 0.71), in the most deprived
      quintile compared with the least deprived 0.52 (0.39, 0.70) and in Asian
      individuals compared with whites 0.62 (0.50, 0.76). Black individuals were
      equally likely to participate as white individuals. Participation was also
      associated with having a co-morbidity or some degree of health limitation. The
      most common reasons for non-participation were considering themselves as being
      too active or lack of time. CONCLUSIONS: Conducting the trial in this diverse
      setting reduced overall response, with lower response in socio-economically
      deprived and Asian sub-groups. Trials with greater reach are likely to be more
      expensive in terms of recruitment and gains in generalizability need to be
      balanced with greater costs. Differential uptake of successful trial
      interventions may increase inequalities in PA levels and should be monitored.
      TRIAL REGISTRATION: ISRCTN.com ISRCTN98538934 . Registered 2nd March 2012.

PMID- 29361930
TI  - Genetic polymorphisms identify in species/biovars of Brucella isolated in China
      between 1953 and 2013 by MLST.
AB  - BACKGROUND: Brucellosis incidence in China is divided into three stages: high
      incidence (1950s-1960s), decline (1970s-1980s), and re-emergence (1990s-2010s).
      At the re-emergence stage, Brucellosis incidence grew exponentially and spread to
      all 32 provinces. We describe the magnitude and the etiological distribution
      changes in mainland China by genotyping data and emphasize its recent
      reemergence. We also provide the genetic diversity and molecular epidemiological
      characteristics of Brucella. RESULTS: From a total of 206 Brucella isolates, 19
      MLST genotypes (STs) were identified and 13 new STs(ST71-83)were found. MLST
      grouped the population into three clusters. B. melitensis, B. abortus and B. suis
      were grouped into cluster 1, 2 and 3 respectively. The predominant genotype in
      the first cluster by MLST, remained unchanged during the three stages. However,
      the proportion of genotypes in the three stages had changed. More isolates were
      clustered in ST8 at the re-emergence stage. STs71-74, which were not found in the
      two former stages, appeared at the re-emergence stage. CONCLUSIONS: The changing
      molecular epidemiology of brucellosis improve our understanding of apparent
      geographic expansion from the historically affected north of China to southern
      provinces in recent reemergence.

PMID- 29361931
TI  - Obstetrical provider knowledge and attitudes towards cell-free DNA screening:
      results of a cross-sectional national survey.
AB  - BACKGROUND: Cell-free DNA (cfDNA) screening has recently acquired tremendous
      attention, promising patients and healthcare providers a more accurate prenatal
      screen for aneuploidy than other current screening modalities. It is unclear how
      much knowledge regarding cfDNA screening obstetrical providers possess which has
      important implications for the quality and content of the informed consent
      patients receive. METHODS: A survey was designed to assess obstetrical provider
      knowledge and attitudes towards cfDNA screening and distributed online through
      the Society of Obstetricians & Gynecologists of Canada (SOGC). Chi-squared tests
      were used to detect differences in knowledge and attitudes between groups.
      RESULTS: 207 respondents completed the survey, composed of 60.6%
      Obstetricians/Gynecologists (OB/GYN), 15.4% Maternal Fetal Medicine (MFM)
      specialists, 16.5% General Practitioners (GP), and 7.5% Midwives (MW). MFM
      demonstrated a significant trend of being most knowledgeable about cfDNA
      screening followed by OB/GYN, GP, and lastly MW in almost all aspects of cfDNA
      screening. All groups demonstrated an overall positive attitude towards cfDNA
      screening; however, OB/GYN and MFM demonstrated a significantly more positive
      attitude than GP and MW. Despite not yet being a diagnostic test, 19.4% of GP
      would offer termination of pregnancy immediately following a positive cfDNA
      screen result compared to none of the MFM and only few OB/GYN or MW. CONCLUSIONS:
      We have demonstrated that different types of obstetrical providers possess
      varying amounts of knowledge regarding cfDNA screening with MFM currently having
      greater knowledge to all other groups. All obstetrical providers must have
      adequate prenatal screening understanding so that we can embrace the benefits of
      this novel and promising technology while protecting the integrity of the
      informed consent process.

PMID- 29361932
TI  - Efficacy of combined treatment with pasireotide, pegvisomant and cabergoline in
      an acromegalic patient resistant to other treatments: a case report.
AB  - BACKGROUND: The approach to acromegalic patients with persistent acromegaly after
      surgery and inadequate response to first-generation somatostatin receptor ligands
      (SRLs) should be strictly tailored. Current options include new pituitary surgery
      and/or radiosurgery, or alternative medical treatment with SRLs high dose
      regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition
      of PEG or cabergoline to SRLs. A new pharmacological approach includes
      pasireotide, a second-generation SRL approved for patients who do not adequately
      respond to surgery and/or for whom surgery is not an option. No reports on
      efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in
      acromegaly are available. CASE PRESENTATION: Here we report the case of a 41-year
      old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant
      to first-generation SRLs both alone and in combination with cabergoline and PEG
      who achieved biochemical and tumor control with the combined triple treatment
      with pasireotide, PEG and cabergoline without adverse events and with a good
      compliance to treatment. CONCLUSIONS: Twelve months of therapy with pasireotide,
      PEG and cabergoline proved to be safe and effective in this particular patient
      and the clinical improvement of disease resulted in an improved compliance to
      treatment.

PMID- 29361933
TI  - Spatial analysis of the death associated factors due oral cancer in Brazil: an
      ecological study.
AB  - BACKGROUND: Oral cancer (OC) is among the ten most common cancers and the seventh
      most frequent cause of death worldwide. It has been reported that these incidence
      rates are higher in developed country and these mortality rates are higher in
      less developed areas. So, the objective of the present study was to analyze the
      spatial joint distribution and to explore possible associations of the
      epidemiological aspects with mortality rates due to OC in the Brazil. METHODS: An
      exploratory ecological study investigated the global spatial autocorrelation of
      epidemiological aspects with mortality rates due to OC from the Brazilian
      Federative Units (FUs) (n = 27) in the period 2005-2014, using the "global" and
      "local" Moran statistic method and a multiple spatial regression, having as
      variables of exposure the habits and lifestyle, sociodemographic indicators, the
      consumption of pesticides, the presence of comorbidities, the use of health
      services and food consumption; and, as a variable response, mortality rates due
      to OC. The software used was Stata 11.0, SPSS 18.0 and GeoDa 0.95-i. RESULTS: The
      spatial distribution of OC mortality rates to age-standard was not random and
      showed high spatial autocorrelation and predominance of significant spatial
      groupings in the Central-South region of Brazil. In the multiple regression,
      statistically negative associations were observed between the Human Development
      Index (HDI) and OC age-standardized in the studied period (p < 0.05) and positive
      associations among the proportion of the population with dental appointment
      within last year, percentage of consumption of oils and fats, percentage of
      consumption of ready-to-eat foods and industrial mixtures and percentage of
      overweight adults with this type of cancer (p < 0.05). CONCLUSION: This is the
      first study that analyzed the factors associated to the spatial clusters of
      mortality due to oral cancer in the Brazilian FUs. A fairly unequal distribution
      of OC mortality rates was found, being that these rates presented inverse
      association with HDI and direct association with dental appointment, consumption
      of oils and fats, ready-to-eat foods and industrial mixtures consumption and
      overweight these rates. It suggests the need to redirect Brazilian public
      policies aimed at combating them so that they cease to be temporary and become
      permanent.

PMID- 29361934
TI  - Using the Medical Research Council framework for development and evaluation of
      complex interventions in a low resource setting to develop a theory-based
      treatment support intervention delivered via SMS text message to improve blood
      pressure control.
AB  - BACKGROUND: Several frameworks now exist to guide intervention development but
      there remains only limited evidence of their application to health interventions
      based around use of mobile phones or devices, particularly in a low-resource
      setting. We aimed to describe our experience of using the Medical Research
      Council (MRC) Framework on complex interventions to develop and evaluate an
      adherence support intervention for high blood pressure delivered by SMS text
      message. We further aimed to describe the developed intervention in line with
      reporting guidelines for a structured and systematic description. METHODS: We
      used a non-sequential and flexible approach guided by the 2008 MRC Framework for
      the development and evaluation of complex interventions. RESULTS: We reviewed
      published literature and established a multi-disciplinary expert group to guide
      the development process. We selected health psychology theory and behaviour
      change techniques that have been shown to be important in adherence and
      persistence with chronic medications. Semi-structured interviews and focus groups
      with various stakeholders identified ways in which treatment adherence could be
      supported and also identified key features of well-regarded messages: polite
      tone, credible information, contextualised, and endorsed by identifiable member
      of primary care facility staff. Direct and indirect user testing enabled us to
      refine the intervention including refining use of language and testing of
      interactive components. CONCLUSIONS: Our experience shows that using a formal
      intervention development process is feasible in a low-resource multi-lingual
      setting. The process enabled us to pre-test assumptions about the intervention
      and the evaluation process, allowing the improvement of both. Describing how a
      multi-component intervention was developed including standardised descriptions of
      content aimed to support behaviour change will enable comparison with other
      similar interventions and support development of new interventions. Even in low
      resource settings, funders and policy-makers should provide researchers with time
      and resources for intervention development work and encourage evaluation of the
      entire design and testing process. TRIAL REGISTRATION: The trial of the
      intervention is registered with South African National Clinical Trials Register
      number (SANCTR DOH-27-1212-386; 28/12/2012); Pan Africa Trial Register
      (PACTR201411000724141; 14/12/2013); ClinicalTrials.gov ( NCT02019823 ;
      24/12/2013).

PMID- 29361935
TI  - Exploring drivers and challenges in implementation of health promotion in
      community mental health services: a qualitative multi-site case study using
      Normalization Process Theory.
AB  - BACKGROUND: There is an increased interest in improving the physical health of
      people with mental illness. Little is known about implementing health promotion
      interventions in adult mental health organisations where many users also have
      physical health problems. The literature suggests that contextual factors are
      important for implementation in community settings. This study focused on the
      change process and analysed the implementation of a structural health promotion
      intervention in community mental health organisations in different contexts in
      Denmark. METHODS: The study was based on a qualitative multiple-case design and
      included two municipal and two regional provider organisations. Data were various
      written sources and 13 semi-structured interviews with 22 key managers and
      frontline staff. The analysis was organised around the four main constructs of
      Normalization Process Theory: Coherence, Cognitive Participation, Collective
      Action, and Reflexive Monitoring. RESULTS: Coherence: Most respondents found the
      intervention to be meaningful in that the intervention fitted well into existing
      goals, practices and treatment approaches. Cognitive Participation: Management
      engagement varied across providers and low engagement impeded implementation.
      Engaging all staff was a general problem although some of the initial resistance
      was apparently overcome. Collective Action: Daily enactment depended on staff
      being attentive and flexible enough to manage the complex needs and varying
      capacities of users. Reflexive Monitoring: During implementation, staff
      evaluations of the progress and impact of the intervention were mostly informal
      and ad hoc and staff used these to make on-going adjustments to activities.
      Overall, characteristics of context common to all providers (work force and user
      groups) seemed to be more important for implementation than differences in the
      external political-administrative context. CONCLUSIONS: In terms of research,
      future studies should adopt a more bottom-up, grounded description of context and
      pay closer attention to the interplay between different dimensions of
      implementation. In terms of practice, future interventions need to better
      facilitate the translation of the initial sense of general meaning into daily
      practice by active local management support that occurs throughout the
      implementation process and that systematically connects the intervention to
      existing practices.

PMID- 29361937
TI  - Changing practice in the assessment and treatment of somatosensory loss in stroke
      survivors: protocol for a knowledge translation study.
AB  - BACKGROUND: The treatment of somatosensory loss in the upper limb after stroke
      has been historically overshadowed by therapy focused on motor recovery. A double
      blind randomized controlled trial has demonstrated the effectiveness of SENSe
      (Study of the Effectiveness of Neurorehabilitation on Sensation) therapy to
      retrain somatosensory discrimination after stroke. Given the acknowledged
      prevalence of upper limb sensory loss after stroke and the evidence-practice gap
      that exists in this area, effort is required to translate the published research
      to clinical practice. The aim of this study is to determine whether evidence
      based knowledge translation strategies change the practice of occupational
      therapists and physiotherapists in the assessment and treatment of sensory loss
      of the upper limb after stroke to improve patient outcomes. METHOD/DESIGN: A
      pragmatic, before-after study design involving eight (n = 8) Australian health
      organizations, specifically sub-acute and community rehabilitation facilities.
      Stroke survivors (n = 144) and occupational therapists and physiotherapists (~10
      per site, ~n = 80) will be involved in the study. Stroke survivors will be
      provided with SENSe therapy or usual care. Occupational therapists and
      physiotherapists will be provided with a multi-component approach to knowledge
      translation including i) tailoring of the implementation intervention to site
      specific barriers and enablers, ii) interactive group training workshops, iii)
      establishing and fostering champion therapists and iv) provision of written
      educational materials and online resources. Outcome measures for occupational
      therapists and physiotherapists will be pre- and post-implementation
      questionnaires and audits of medical records. The primary outcome for stroke
      survivors will be change in upper limb somatosensory function, measured using a
      standardized composite measure. DISCUSSION: This study will provide evidence and
      a template for knowledge translation in clinical, organizational and policy
      contexts in stroke rehabilitation. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry (ANZCTR) retrospective registration ACTRN12615000933550
      .

PMID- 29361936
TI  - Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal
      sepsis and is exacerbated by erythromycin.
AB  - BACKGROUND: Preterm prelabour rupture of the fetal membranes (PPROM) precedes 30%
      of preterm births and is a risk factor for early onset neonatal sepsis. As PPROM
      is strongly associated with ascending vaginal infection, prophylactic antibiotics
      are widely used. The evolution of vaginal microbiota compositions associated with
      PPROM and the impact of antibiotics on bacterial compositions are unknown.
      METHODS: We prospectively assessed vaginal microbiota prior to and following
      PPROM using MiSeq-based sequencing of 16S rRNA gene amplicons and examined the
      impact of erythromycin prophylaxis on bacterial load and community structures.
      RESULTS: In contrast to pregnancies delivering at term, vaginal dysbiosis
      characterised by Lactobacillus spp. depletion was present prior to the rupture of
      fetal membranes in approximately a third of cases (0% vs. 27%, P = 0.026) and
      persisted following membrane rupture (31%, P = 0.005). Vaginal dysbiosis was
      exacerbated by erythromycin treatment (47%, P = 0.00009) particularly in women
      initially colonised by Lactobacillus spp. Lactobacillus depletion and increased
      relative abundance of Sneathia spp. were associated with subsequent funisitis and
      early onset neonatal sepsis. CONCLUSIONS: Our data show that vaginal microbiota
      composition is a risk factor for subsequent PPROM and is associated with adverse
      short-term maternal and neonatal outcomes. This highlights vaginal microbiota as
      a potentially modifiable antenatal risk factor for PPROM and suggests that
      routine use of erythromycin for PPROM be re-examined.

PMID- 29361938
TI  - Long-term effects of Garcinia cambogia/Glucomannan on weight loss in people with
      obesity, PLIN4, FTO and Trp64Arg polymorphisms.
AB  - BACKGROUND: Overweight and obesity are considered major health problems that
      contribute to increase mortality and quality of life. Both conditions have a high
      prevalence across the world reaching epidemic numbers. Our aim was to evaluate
      the effects of the administration of Garcinia cambogia (GC) and Glucomannan (GNN)
      on long-term weight loss in people with overweight or obesity. METHODS:
      Prospective, not-randomized controlled intervention trial was conducted. We
      treated 214 subjects with overweight or obesity with GC and GNN (500 mg twice a
      day, each) for 6 months evaluating weight, fat mass, visceral fat, basal
      metabolic rate, and lipid and glucose blood profiles comparing them with basal
      values. Some patients were carriers of polymorphisms PLIN4 -11482G > A-, fat mass
      and obesity-associated (FTO) -rs9939609 A/T- and beta-adrenergic receptor 3
      (ADRB3) -Trp64Arg. RESULTS: Treatment produced weight loss, reducing fat mass,
      visceral fat, lipid and blood glucose profiles while increasing basal metabolic
      rate. Results were independent of sex, age or suffering from hypertension,
      diabetes mellitus type 2 or dyslipidemia and were attenuated in carriers of
      PLIN4, FTO, Trp64Arg polymorphisms. CONCLUSIONS: Administration of GC and GNN
      reduce weight and improve lipid and glucose blood profiles in people with
      overweight or obesity, although the presence of polymorphisms PLIN4, FTO and
      ADRB3 might hinder in some degree these effects. ISRCTN78807585, 19 September
      2017, retrospective study.

PMID- 29361939
TI  - Efficacy and safety of artemisinin-based combination therapy and chloroquine with
      concomitant primaquine to treat Plasmodium vivax malaria in Brazil: an open label
      randomized clinical trial.
AB  - BACKGROUND: There is general international agreement that the importance of vivax
      malaria has been neglected, and there is a need for new treatment approaches in
      an effort to progress towards control and elimination in Latin America. This open
      label randomized clinical trial evaluated the efficacy and safety of three
      treatment regimens using either one of two fixed dose artemisinin-based
      combinations or chloroquine in combination with a short course of primaquine (7-9
      days: total dose 3-4.2 mg/kg) in Brazil. The primary objective was establishing
      whether cure rates above 90% could be achieved in each arm. RESULTS: A total of
      264 patients were followed up to day 63. The cure rate of all three treatment
      arms was greater than 90% at 28 and 42 days. Cure rates were below 90% in all
      three treatment groups at day 63, although the 95% confidence interval included
      90% for all three treatments. Most of the adverse events were mild in all
      treatment arms. Only one of the three serious adverse events was related to the
      treatment and significant drops in haemoglobin were rare. CONCLUSION: This study
      demonstrated the efficacy and safety of all three regimens that were tested with
      42-day cure rates that meet World Health Organization criteria. The efficacy and
      safety of artemisinin-based combination therapy regimens in this population
      offers the opportunity to treat all species of malaria with the same regimen,
      simplifying protocols for malaria control programmes and potentially contributing
      to elimination of both vivax and falciparum malaria. Trial registration RBR
      79s56s.

PMID- 29361940
TI  - Plasmodium falciparum genetic variation of var2csa in the Democratic Republic of
      the Congo.
AB  - BACKGROUND: The Democratic Republic of the Congo (DRC) bears a high burden of
      malaria, which is exacerbated in pregnant women. The VAR2CSA protein plays a
      crucial role in pregnancy-associated malaria (PAM), and hence quantifying
      diversity at the var2csa locus in the DRC is important in understanding the basic
      epidemiology of PAM, and in developing a robust vaccine against PAM. METHODS:
      Samples were taken from the 2013-14 Demographic and Health Survey conducted in
      the DRC, focusing on children under 5 years of age. A short subregion of the
      var2csa gene was sequenced in 115 spatial clusters, giving country-wide estimates
      of sequence polymorphism and spatial population structure. RESULTS: Results
      indicate that var2csa is highly polymorphic, and that diversity is being
      maintained through balancing selection, however, there is no clear signal of
      phylogenetic or geographic structure to this diversity. Linear modelling
      demonstrates that the number of var2csa variants in a cluster correlates directly
      with cluster prevalence, but not with other epidemiological factors such as
      urbanicity. CONCLUSIONS: Results suggest that the DRC fits within the global
      pattern of high var2csa diversity and little genetic differentiation between
      regions. A broad multivalent VAR2CSA vaccine candidate could benefit from
      targeting stable regions and common variants to address the substantial genetic
      diversity.

PMID- 29361941
TI  - Physicians' perspectives on clinical pharmacy services in Northern Sweden: a
      qualitative study.
AB  - BACKGROUND: In many countries, clinical pharmacists are part of health care teams
      that work to optimize drug therapy and ensure patient safety. However, in Sweden,
      clinical pharmacy services (CPSs) in hospital settings have not been widely
      implemented and regional differences exist in the uptake of these services.
      Physicians' attitudes toward CPSs and collaborating with clinical pharmacists may
      facilitate or hinder the implementation and expansion of the CPSs and the role of
      the clinical pharmacist in hospital wards. The aim of this study was to explore
      physicians' perceptions regarding CPSs performed at hospital wards in Northern
      Sweden. METHODS: Face-to-face semi-structured interviews were conducted with a
      purposive sample of nine physicians who had previously worked with clinical
      pharmacists between November 2014 and January 2015. Interviews were digitally
      recorded, transcribed and analysed using a constant comparison method. RESULTS:
      Different themes emerged regarding physicians' views of clinical pharmacy; two
      main interlinked themes were service factors and pharmacist factors. The service
      was valued and described in a positive way by all physicians. It was seen as an
      opportunity for them to learn more about pharmacological treatment and also an
      opportunity to discuss patient medication treatment in detail. Physicians
      considered that CPSs could improve patient outcomes and they valued continuity
      and the ability to build a trusting relationship with the pharmacists over time.
      However, there was a lack of awareness of the CPSs. All physicians knew that one
      of the pharmacist's roles is to conduct medication reviews, but most of them were
      only able to describe a few elements of what this service encompasses.
      Pharmacists were described as "drug experts" and their recommendations were
      perceived as clinically relevant. Physicians wanted CPSs to continue and to be
      implemented in other wards. CONCLUSIONS: All physicians were positive regarding
      CPSs and were satisfied with the collaboration with the clinical pharmacists.
      These findings are important for further implementation and expansion of CPSs,
      particularly in Northern Sweden.

PMID- 29361942
TI  - IL-1beta mediates lung neutrophilia and IL-33 expression in a mouse model of
      viral-induced asthma exacerbation.
AB  - BACKGROUND: Viral-induced asthma exacerbations, which exhibit both Th1-type
      neutrophilia and Th2-type inflammation, associate with secretion of Interleukin
      (IL)-1beta. IL-1beta induces neutrophilic inflammation. It may also increase Th2
      type cytokine expression. We hypothesised that IL-1beta is causally involved in
      both Th1 and Th2 features of asthma exacerbations. This hypothesis is tested in
      our mouse model of viral stimulus-induced asthma exacerbation. METHOD: Wild-type
      (WT) and IL-1beta deficient (IL-1beta-/-) mice received house dust mite (HDM) or
      saline intranasally during three weeks followed by intranasal dsRNA (PolyI:C
      molecule known for its rhinovirus infection mimic) for three consecutive days to
      provoke exacerbation. Bronchoalveolar lavage fluid was analysed for inflammatory
      cells and total protein. Lung tissues were stained for neutrophilic inflammation
      and IL-33. Tissue homogenates were analysed for mRNA expression of Muc5ac,
      CXCL1/KC, TNF-alpha, CCL5, IL-25, TSLP, IL-33, IL-1beta, CCL11 and CCL2 using RT
      qPCR. RESULTS: Expression of IL-1beta, neutrophil chemoattractants, CXCL1 and
      CCL5, the Th2-upstream cytokine IL-33, and Muc5ac were induced at exacerbation in
      WT mice and were significantly inhibited in IL-1beta-/- mice at exacerbation.
      Effects of HDM alone were not reduced in IL-1beta-deficient mice. CONCLUSION:
      Without being involved in the baseline HDM-induced allergic asthma, IL-1beta
      signalling was required to induce neutrophil chemotactic factors, IL-33, and
      Muc5ac expression at viral stimulus-induced exacerbation. We suggest that IL
      1beta has a role both in neutrophilic and Th2 inflammation at viral-induced
      asthma exacerbations.

PMID- 29361943
TI  - Identification of danthron as an isoform-specific inhibitor of HEME OXYGENASE
      1/cytochrome P450 reductase interaction with anti-tumor activity.
AB  - BACKGROUND: Heme oxygenase (HO) catalyzes NADPH-dependent degradation of heme to
      liberate iron, carbon monoxide and biliverdin. The interaction between HO and
      cytochrome P450 reductase (CPR), an electron donor, is essential for HO activity.
      HO-1 is a stress-inducible isoform whereas HO-2 is constitutively expressed. HO-1
      induction is commonly seen in cancers and impacts disease progression, supporting
      the possibility of targeting HO-1 for cancer therapy. METHODS: We employed a cell
      based bioluminescence resonance energy transfer assay to screen compounds with
      ability to inhibit HO-1/CPR interaction. The effect of the identified compound on
      HO-1/CPR interaction was confirmed by pull down assay. Moreover, the anti
      tumorigenic activity of the identified compound on HO-1-enhanced tumor growth and
      migration was assessed by trypan blue exclusion method and wound healing assay.
      RESULTS: Danthron was identified as an effective small molecule able to interfere
      with the interaction between HO-1 and CPR but not HO-2 and CPR. Additional
      experiments with structural analogues of danthron revealed that the positions of
      hydroxyl moieties significantly affected the potency of inhibition on HO-1/CPR
      interaction. Pull-down assay confirmed that danthron inhibited the interaction of
      CPR with HO-1 but not HO-2. Danthron suppressed growth and migration of HeLa
      cells with stable HO-1 overexpression but not mock cells. In contrast,
      anthrarufin, a structural analog with no ability to interfere HO-1/CPR
      interaction, exhibited no significant effect on HO-1-overexpressing HeLa cells.
      CONCLUSIONS: These findings demonstrate that danthron is an isoform-specific
      inhibitor for HO-1/CPR interaction and may serve as a lead compound for novel
      anticancer drug.

PMID- 29361944
TI  - Co-contraction characteristics of lumbar muscles in patients with lumbar disc
      herniation during different types of movement.
AB  - BACKGROUND: Muscular performance is an important factor for the mechanical
      stability of lumbar spine in humans, in which, the co-contraction of lumbar
      muscles plays a key role. We hypothesized that when executing different daily
      living motions, the performance of the lumbar muscle co-contraction stabilization
      mechanism varies between patients with lumbar disc herniation (LDH) and healthy
      controls. Hence, in this study, co-contraction performance of lumbar muscles
      between patients with LDH and healthy subjects was explored to check if there are
      significant differences between the two groups when performing four
      representative movements. METHODS: Twenty-six LDH patients (15 females, 11 males)
      and a control group of twenty-eight subjects (16 females, 12 males) were
      recruited. Surface electromyography (EMG) signals were recorded from the external
      oblique, lumbar multifidus, and internal oblique/transversus abdominis muscles
      during the execution of four types of movement, namely: forward bending, backward
      bending, left lateral flexion and right lateral flexion. The acquired EMG signals
      were segmented, and wavelet decomposition was performed followed by
      reconstruction of the low-frequency components of the signal. Then, the
      reconstructed signals were used for further analysis. Co-contraction ratio was
      employed to assess muscle coordination and compare it between the LDH patients
      and healthy controls. The corresponding signals of the subjects in the two groups
      were compared to evaluate the differences in agonistic and antagonistic muscle
      performance during the different motions. Also, sample entropy was applied to
      evaluate complexity changes in lumbar muscle recruitment during the movements.
      RESULTS: Significant differences between the LDH and control groups were found in
      the studied situations (p < 0.05). During the four movements considered in this
      study, the participants of the LDH group exhibited a higher level of co
      contraction ratio, lower agonistic, and higher antagonistic lumbar muscle
      activity (p < 0.01) than those of the control group. Furthermore, the co
      contraction ratio of LDH patients was dominated by the antagonistic muscle
      activity during the movements, except for the forward bending motion. However, in
      the healthy control group, the agonistic muscle activity contributed more to the
      co-contraction ratio with an exception for the backward bending motion.
      Conversely, the sample entropy value was significantly lower for agonistic
      muscles of LDH group compared to the control group (p < 0.01) while the entropy
      value was significantly greater in antagonistic muscles (p < 0.01) during the
      four types of movement, respectively. CONCLUSIONS: Lumbar disc herniation
      patients exhibited numerous variations in the evaluated parameters that reflect
      the co-contraction of lumbar muscles, the agonistic and antagonistic muscle
      activities, and their respective sample entropy values when compared with the
      healthy control group. These variations could be due to the compensation
      mechanism that was required to stabilize the spine. The results of this study
      could facilitate the design of efficient rehabilitation methods for treatment of
      lumbar muscle dysfunctions.

PMID- 29361947
TI  - Adolescents' reproductive health knowledge, choices and factors affecting
      reproductive health choices: a qualitative study in the West Gonja District in
      Northern region, Ghana.
AB  - BACKGROUND: In Ghana, adolescents constitute about a quarter of the total
      population. These adolescents make reproductive health decisions and choices
      based on their knowledge and the availability of such choices. These reproductive
      health decisions and choices can either negatively or positively affect their
      lives. This study therefore explored adolescents' reproductive health knowledge
      and choices, the type of choices they make and the factors that affect these
      choices. METHODS: This qualitative study adopted a narrative approach to
      qualitative enquiry. Eight focus group discussions (N = 80) were conducted among
      both in-school and out-of-school adolescents aged 10-19 years. The discussions
      were stratified by sex and studentship. In addition, nine in-depth interviews
      were conducted with various stakeholders in reproductive health services and
      community opinion leaders. Both the focus group discussions and in-depth
      interviews were recorded, transcribed and analysed using NVivo 11. Thematic
      analysis was employed in analysing data. RESULTS: The study found that knowledge
      on reproductive health choices was low among respondents with majority of them
      relying on their peers for information on sexual and reproductive health. Having
      a sexual partner(s) and engaging in premarital sex was common and viewed as
      normal. Adolescents engaged in unprotected sexual practices as a way of testing
      their fertility, assurance of love, bait for marriage and for livelihood.
      Inserting herbs into the vagina, drinking concoctions and boiled pawpaw leaves
      were identified as local methods employed by adolescents to induce abortion.
      Reproductive health services were available in the community but received low
      utilization because of perceived negative attitude of health workers,
      confidentiality and social norms. CONCLUSIONS: Adolescents in this study
      generally engaged in risky reproductive health choices that can negatively affect
      their reproductive health. Adolescents in this part of Ghana have challenges
      utilizing available reproductive health services because of socio-cultural and
      health system barriers.

PMID- 29361946
TI  - The prognostic value of preoperative prognostic nutritional index in patients
      with hypopharyngeal squamous cell carcinoma: a retrospective study.
AB  - BACKGROUND: To analyze the prognostic value of preoperative prognostic
      nutritional index (PNI) in predicting the survival outcome of hypopharyngeal
      squamous cell carcinoma (HPSCC) patients receiving radical surgery. METHODS: From
      March 2006 to August 2016, 123 eligible HPSCC patients were reviewed. The
      preoperative PNI was calculated as serum albumin (g/dL) * 10 + total lymphocyte
      count (mm-3) * 0.005. These biomarkers were measured within 2 weeks prior to
      surgery. The impact of preoperative PNI on overall survival (OS), progression
      free survival (PFS), locoregional recurrence-free survival (LRFS) and distant
      metastasis-free survival (DMFS) were analyzed using Kaplan-Meier method and Cox
      proportional hazards model. RESULTS: Median value of 52.0 for the PNI was
      selected as the cutoff point. PNI value was then classified into two groups: high
      PNI (> 52.0) versus low PNI (<= 52.0). Multivariate analysis showed that high
      preoperative PNI was an independent prognostic factor for better OS (P = 0.000),
      PFS (P = 0.001), LRFS (P = 0.005) and DMFS (P = 0.016). CONCLUSIONS: High PNI
      predicts superior survival in HPSCC patients treated with radical surgery. As
      easily accessible biomarkers, preoperative PNI together with the conventional TNM
      staging system can be utilized to enhance the accuracy in predicting survival and
      determining therapy strategies in these patients.

PMID- 29361948
TI  - School feeding program has resulted in improved dietary diversity, nutritional
      status and class attendance of school children.
AB  - BACKGROUND: School Feeding Program (SFP) is a targeted safety net program
      designed to provide educational and health benefits to vulnerable children.
      However, limited evidence exists regarding the effect of the intervention on the
      nutritional status and school attendance of children. The study is aimed at
      examining the effects of SFP on dietary diversity, nutritional status and class
      attendance of school children in Boricha district, Southern Ethiopia. METHODS:
      The study was conducted based on a representative data collected from 290
      students drawn from the district. A school-based comparative cross-sectional
      study was conducted on school children aged 10-14 years. Data were collected
      using structured pretested questionnaire. The effects of SFP on dietary diversity
      score (DDS), class attendance rate, body-mass-index for age (BAZ) and height-for
      age (HAZ) Z-scores were assessed using multivariable linear regression model.
      RESULTS: The finding showed significantly higher mean (+/-SD) of DDS in SFP
      beneficiaries (5.8 +/- 1.1) than the non-beneficiaries (3.5 +/- 0.7) (P < 0.001).
      BAZ and HAZ of the beneficiaries were also higher than their counterparts, which
      were (0.07 +/- 0.93), (- 0.50 +/- 0.86) and (- 1.45 +/- 1.38), (- 2.17 +/- 1.15)
      respectively (P < 0.001). The mean (+/-SD) days of absence from school for non
      beneficiaries (2.6 +/- 1.6) was significantly higher than that of the
      beneficiaries (1.3 +/- 1.7) (P < 0.05). CONCLUSION: Given the positive effects of
      the program in improving the DDS, nutritional status, and class attendance of
      school children, we strongly recommend scaling up the program to other food
      insecure areas.

PMID- 29361945
TI  - Adjunctive therapy for severe malaria: a review and critical appraisal.
AB  - BACKGROUND: Despite recent efforts and successes in reducing the malaria burden
      globally, this infection still accounts for an estimated 212 million clinical
      cases, 2 million severe malaria cases, and approximately 429,000 deaths annually.
      Even with the routine use of effective anti-malarial drugs, the case fatality
      rate for severe malaria remains unacceptably high, with cerebral malaria being
      one of the most life-threatening complications. Up to one-third of cerebral
      malaria survivors are left with long-term cognitive and neurological deficits.
      From a population point of view, the decrease of malaria transmission may
      jeopardize the development of naturally acquired immunity against the infection,
      leading to fewer total cases, but potentially an increase in severe cases. The
      pathophysiology of severe and cerebral malaria is not completely understood, but
      both parasite and host determinants contribute to its onset and outcomes.
      Adjunctive therapy, based on modulating the host response to infection, could
      help to improve the outcomes achieved with specific anti-malarial therapy.
      RESULTS AND CONCLUSIONS: In the last decades, several interventions targeting
      different pathways have been tested. However, none of these strategies have
      demonstrated clear beneficial effects, and some have shown deleterious outcomes.
      This review aims to summarize evidence from clinical trials testing different
      adjunctive therapy for severe and cerebral malaria in humans. It also highlights
      some preclinical studies which have evaluated novel strategies and other
      candidate therapeutics that may be evaluated in future clinical trials.

PMID- 29361949
TI  - miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a.
AB  - BACKGROUND: High frequency of recurrence is the major cause of the poor outcomes
      for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged
      as a high-priority miRNA in HCC and was found to be related to HCC metastasis.
      Whether the expression of miR-182-5p in tumor tissue correlated with early
      recurrence in HCC patients underwent curative surgery was unknown. METHODS: Real
      time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the
      expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8),
      transwell assays were performed to detected cells proliferation and migration
      ability. Flow cytometry assays were used to detect cell apoptosis rate, and
      xenograft model was employed to study miR-182-5p in HCC growth and lung
      metastasis. The target of miR-182-5p was validated with a dual-luciferase
      reporter assay and western blotting. Immunohistochemistry, immumoblotting, and
      immunoprecipitation were performed to test relative protein expression. RESULTS:
      We showed that high expression of miR-182-5p in tumor tissues correlated with
      poor prognosis as well as early recurrence in HCC patients underwent curative
      surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in
      vitro and in vivo. miR-182-5p directly targets 3'-UTR of FOXO3a and repressed
      FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation.
      Notably, miR-182-5p activated Wnt/beta-catenin signaling by inhibiting the
      degradation of beta-catenin and enhancing the interaction between beta-catenin
      and TCF4 which was mediated by repressed FOXO3a. CONCLUSIONS: Consistently, miR
      182-5p can be a potential predictor of early recurrence for HCC patients
      underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced
      HCC progression.

PMID- 29361950
TI  - Health-related quality of life among long-term (>=5 years) prostate cancer
      survivors by primary intervention: a systematic review.
AB  - BACKGROUND: Due to an improving prognosis, and increased knowledge of
      intervention effects over time, long-term well-being among prostate cancer (PC)
      survivors has gained increasing attention. Yet, despite a variety of available PC
      interventions, experts currently disagree on optimal intervention course based on
      survival rates. METHODS: In January 2017, we searched multiple databases to
      identify relevant articles. Studies were required to assess at least two
      different dimensions of health-related quality of life (HRQoL) in PC survivors
      >=5 years past diagnosis with validated measures. RESULTS: Identified studies (n
      = 13) were mainly observational cohort studies (n = 10), conducted in developed
      countries with a sample size below 100 per study arm (n = 6). External-beam
      radiation therapy was the most common intervention (n = 12), whereas only three
      studies included patients on active surveillance or on watchful waiting. Studies
      were largely heterogeneous in cancer stage at diagnosis, intervention groups and
      instruments. All identified studies either used the EORTC QLQ-C30 (n = 5) or the
      SF-36 (n = 7) to assess generic HRQoL, yet 11 different instruments were employed
      to assess PC specific urinary, bowel and sexual symptoms. Overall, no consistent
      pattern between intervention and HRQoL was observed. Results from two randomized
      controlled-trials (RCTs) and one observational study, comparing HRQoL by primary
      intervention in localized PC survivors suggest that long-term HRQoL does not
      differ by intervention. However, observational studies that included a
      combination of localized and locally advanced stage PC survivors identified HRQoL
      differences for various scales including physical well-being, social and role
      function, vitality, and role emotional. CONCLUSION: This review reveals the
      number of publications comparing HRQoL by primary intervention in long-term PC
      survivors is currently limited. Robust data from two RCTs and one observational
      study suggest that HRQoL does not seem to differ by intervention. However, the
      heterogeneity of studies' methodologies and results hindered our ability to draw
      a clear conclusion. Therefore, in order to answer the question of which primary
      intervention is superior with respect to long-term HRQoL in PC patients, more
      high-quality, large-scale prospective cohort studies, or RCTs with repeated HRQoL
      assessments, are urgently needed.

PMID- 29361951
TI  - Implementation lessons for school food policies and marketing restrictions in the
      Philippines: a qualitative policy analysis.
AB  - BACKGROUND: The school environment can enhance children's skills, knowledge and
      behaviours in relation to healthy eating. However, in many countries, unhealthy
      foods are commonly available in schools, and children can be exposed to
      aggressive marketing by the food industry. Taking the perspective of
      policymakers, this study aimed to identify barriers and enablers to effective
      school food policy development and implementation in the Philippines. METHODS: In
      May 2016, semi-structured interviews were conducted with 21 policymakers and
      stakeholders involved in school food policymaking and implementation in the
      Philippines. The Health Policy Analysis Triangle was used to identify interview
      questions and to guide the thematic analysis. These included the political and
      socio-environmental context, strengths and limitations of existing policy
      content, roles and behaviours of actors, implementation processes, policy
      outcomes, and opportunities to improve policy coherence. RESULTS: The Department
      of Education's policy 'Orders' represented a relatively strong policy framework
      for the education sector of the Philippines. However, a lack of human and
      financial resources for implementation, planning, and policy enforcement limited
      the impact of the policy on the healthiness of school food provision. Ambiguity
      in policy wording allowed a wide interpretation of the foods eligible to be
      provided in schools, and led to difficulties in effective monitoring and
      enforcement. Food companies used existing relationships with schools to promote
      their brands and compromise the establishment of a stronger food policy agenda.
      We found a motivated group of actors engaging in policy-oriented learning and
      advocating for a stronger policy alternative so as to improve the school food
      environment. CONCLUSIONS: The adoption of policy mechanisms being used to promote
      healthy dietary practices in the school setting will be strengthened by more
      robust implementation planning processes, and resources to support implementation
      and enforcement. Policymakers should ensure policy language clearly and
      unequivocally promotes healthier food and beverage options. Steps should be taken
      to achieve policy coherence by ensuring the objectives of one agency or
      institution are not undermining that of any others. Where there is reliance on
      the private sector for school resources, safeguards should be established to
      protect against conflicts of interest.

PMID- 29361952
TI  - Overweight/obesity among school aged children in Bahir Dar City: cross sectional
      study.
AB  - BACKGROUND: Developing countries, including Ethiopia are experiencing a double
      burden of malnutrition. There is limited information about prevalence of
      overweight/obesity among school aged children in Ethiopia particularly in Bahir
      Dar city. Hence this study aimed to assess the prevalence of overweight/obesity
      and associated factors among school children aged 6-12 years at Bahir Dar City,
      Northwest Ethiopia. METHODS: A school based cross-sectional study was carried
      out. A total of 634 children were included in the study. Multi stage systematic
      random sampling technique was used. A multivariable logistic regression analysis
      was used to identify factors associated with overweight/obesity. The association
      between dependent and independent variables were assessed using odds ratio with
      95% confidence interval and p-value <=0.05 was considered statistically
      significant. RESULTS: The overall prevalence of overweight and/or obesity was
      11.9% (95% CI, 9.3, 14.4) (out of which 8.8% were overweight and 3.1% were
      obese). Higher wealth status[adjusted OR = 3.14, 95% CI:1.17, 8.46], being a
      private school student [AOR = 2.21, 95% CI:1.09, 4.49], use of transportation to
      and from school [AOR = 2.53, 95% CI: 1.26,5.06], fast food intake [AOR = 3.88,
      95% CI: 1.42,10.55], lack of moderate physical activity [AOR = 2.87, 95% CI:
      1.21,6.82], low intake of fruit and vegetable [AOR = 6.45, 95% CI:3.19,13.06]
      were significant factors associated with overweight and obesity. CONCLUSION: This
      study revealed that prevalence of overweight/obesity among school aged children
      in Bahir Dar city is high. Thus, promoting healthy dietary habit, particularly
      improving fruit and vegetable intake is essential to reduce the burden of
      overweight and obesity. Furthermore, it is important to strengthen nutrition
      education about avoiding junk food consumption and encouraging regular physical
      activity.

PMID- 29361953
TI  - Breaking bad news to antenatal patients with strategies to lessen the pain: a
      qualitative study.

PMID- 29361954
TI  - Perceived barriers to early detection of breast cancer in Wakiso District, Uganda
      using a socioecological approach.
AB  - BACKGROUND: Early detection of breast cancer is known to improve its prognosis.
      However, women in most low and middle income countries, including Uganda, do not
      detect it early hence present at an advanced stage. This study investigated the
      perceived barriers to early detection of breast cancer in Wakiso district, Uganda
      using a multilevel approach focused through a socioecological framework. METHODS:
      Using qualitative methods, participants were purposively selected to take part in
      the study. 5 semi-structured interviews were conducted among the community
      members while two focus groups were conducted amongst women's group and community
      health workers (CHWs) in Ssisa sub county, Wakiso district. In addition, 7 key
      informant interviews with health professionals, policy makers and public health
      researchers were carried out. RESULTS: Findings from the study revealed that
      barriers to early detection of breast cancer are multifaceted and complex,
      cutting across individual, interpersonal, organizational, community and policy
      barriers. The major themes that emerged from the study included: knowledge,
      attitudes, beliefs and practices (KABP); health system and policy constraints;
      and structural barriers. Prominent barriers associated with KABP were low
      knowledge, apathy, fear and poor health seeking behaviours. Barriers within the
      health systems and policy arenas were mostly centred around competing health care
      burdens within the country, lack of a cancer policy and weak primary health care
      capacity in Wakiso district. Distance, poverty and limited access to media were
      identified as the most prominent structural barriers. CONCLUSION: Barriers to
      early detection of breast cancer are complex and go beyond individual behaviours.
      These barriers interact across multiple levels of influence such as
      organizational, community and policy. The findings of this study could provide
      opportunities for investment in multi-level interventions.

PMID- 29361955
TI  - Intracystic papillary carcinoma of the male breast: a case report.
AB  - BACKGROUND: Intracystic papillary carcinoma (IPC) is defined as cancer that
      develops from the wall of a cyst in the breast. As breast cancer in men accounts
      for only 1% of all breast cancers, male IPC is an extremely rare form of the
      disease. The present case report examines IPC in a man, along with an in-depth
      literature discussion. CASE PRESENTATION: A 64-year-old Japanese man noticed a
      mass in the right breast and sought medical attention. An elastic and soft
      neoplastic 3-cm lesion was palpated in the right papilla. As a 1-cm solid tumor
      with a gradual rise from the cyst wall was confirmed within the cyst, vacuum
      assisted biopsy (VAB) was performed on that site. Pathological examination of the
      biopsy revealed heterotypic cells with an enlarged oval nucleus forming dense
      papillary structures mainly of vascular connective tissue component. Contrast
      enhanced computed tomography (CT) confirmed thickening of the wall that protruded
      outside the cyst. The preoperative diagnosis was right breast cancer (male IPC)
      TisN0M0 stage 0 luminal B-like. Total mastectomy and sentinel lymph node biopsy
      were performed. In the excised specimen, a 4.0-cm unilocular cyst was found,
      along with a 1-cm solid tumor with a gradual rise from the cyst wall.
      Pathological diagnosis of the resected specimen shared similar characteristics
      with the solid tumor in the cyst: notably, an oval nucleus with histologically
      clear nucleolus and fine granular chromatin, cylindrically shaped heterotypic
      cells, and the presence of basophilic cells in the papillary growth with a thin
      stem of fibrovasculature as the axis. Some invasion of tumor cells into the
      interstitium was confirmed. As such, the final diagnosis was right breast cancer
      (male IPC) T2N0M0 stage IIA luminal B-like. The expression of hormone receptor
      (ER and PgR) was high, and endocrine therapy was initiated postoperatively (20
      mg/day tamoxifen). At the present time (3 months postoperation), there has not
      been any evidence of metastasis. CONCLUSIONS: We reported a rare case of an IPC
      in the male breast, along with a literature review.

PMID- 29361956
TI  - The effects of surgical treatment with chondroblastoma in children and
      adolescents in open epiphyseal plate of long bones.
AB  - BACKGROUND: Chondroblastoma is a rare benign cartilaginous tumor, which primarily
      occurs in children and adolescents. Chondroblastoma commonly originates in the
      epiphyseal plate of long bones. An aggressive curettage treatment is recommended
      to manage lesion, which may jeopardize an open epiphyseal plate and result in
      limb shortening and deformity as the limb grows and develops. The purpose is to
      observe surgical effects of chondroblastoma on open epiphyseal plate of long
      bones in children and adolescents and explore influences on limb growth and
      development. METHODS: We retrospectively reviewed 18 cases of long bone
      chondroblastoma with open epiphyseal growth plate during March 2004 to October
      2010 in our center. Seven females and 11 males with mean age of 11.6 +/- 2.0
      years old (8-15 years) were included. Patients, who suffered from trauma and
      pathological fracture of the epiphyseal plate or congenital diseases such as
      poliomyelitis, congenital dementia, and cartilage malnutrition, were excluded.
      All patients were treated with meticulous intralesional curettage and inactivity
      with alcohol followed by bone grafts. All cases were followed up 8.2 +/- 1.7
      years (5-11.5 years). RESULTS: All had no local recurrence and distance
      metastasis. The length of the affected limb was short, 18.47 +/- 7.22 mm (1.5-30
      mm). There was no obvious relativity with tumor activity (P = 0.061). Meanwhile,
      there were obvious relativity with the greatest dimension of the lesion (TGD) (P
      = 0.003), the vertical dimension between edge of lesion and epiphyseal line (TVD)
      (P = 0.010), and area ratio of lesion to local epiphysis (lesion/growth plate) (P
      = 0.015). The MSTS93 (Revised Musculoskeletal Tumor Society Rating Scale 93) and
      SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey) had been
      significantly improved (P < 0.01). CONCLUSION: Managing of chondroblastoma
      located in open epiphyseal plate of a long bone with meticulous curettage,
      inactivity, and bone grafts can control tumor progression and recurrence
      effectively. Meanwhile, early detection and prompt surgical treatment
      intervention, which reduced significantly the tumor to influence limb growth and
      development, get encouraging limb function. TRIAL REGISTRATION: This is a
      retrospective study, which was not registered in any trial registry.

PMID- 29361958
TI  - Ethnic bias and clinical decision-making among New Zealand medical students: an
      observational study.
AB  - BACKGROUND: Health professional racial/ethnic bias may impact on clinical
      decision-making and contribute to subsequent ethnic health inequities. However,
      limited research has been undertaken among medical students. This paper presents
      findings from the Bias and Decision-Making in Medicine (BDMM) study, which sought
      to examine ethnic bias (Maori (indigenous peoples) compared with New Zealand
      European) among medical students and associations with clinical decision-making.
      METHODS: All final year New Zealand (NZ) medical students in 2014 and 2015 (n =
      888) were invited to participate in a cross-sectional online study. Key
      components included: two chronic disease vignettes (cardiovascular disease (CVD)
      and depression) with randomized patient ethnicity (Maori or NZ European) and
      questions on patient management; implicit bias measures (an ethnicity preference
      Implicit Association Test (IAT) and an ethnicity and compliant patient IAT); and,
      explicit ethnic bias questions. Associations between ethnic bias and clinical
      decision-making responses to vignettes were tested using linear regression.
      RESULTS: Three hundred and two students participated (34% response rate).
      Implicit and explicit ethnic bias favoring NZ Europeans was apparent among
      medical students. In the CVD vignette, no significant differences in clinical
      decision-making by patient ethnicity were observed. There were also no
      differential associations by patient ethnicity between any measures of ethnic
      bias (implicit or explicit) and patient management responses in the CVD vignette.
      In the depression vignette, some differences in the ranking of recommended
      treatment options were observed by patient ethnicity and explicit preference for
      NZ Europeans was associated with increased reporting that NZ European patients
      would benefit from treatment but not Maori (slope difference 0.34, 95% CI 0.08,
      0.60; p = 0.011), although this was the only significant finding in these
      analyses. CONCLUSIONS: NZ medical students demonstrated ethnic bias, although
      overall this was not associated with clinical decision-making. This study both
      adds to the small body of literature internationally on racial/ethnic bias among
      medical students and provides relevant and important information for medical
      education on indigenous health and ethnic health inequities in New Zealand.

PMID- 29361957
TI  - Two-step interphase microtubule disassembly aids spindle morphogenesis.
AB  - BACKGROUND: Entry into mitosis triggers profound changes in cell shape and
      cytoskeletal organisation. Here, by studying microtubule remodelling in human
      flat mitotic cells, we identify a two-step process of interphase microtubule
      disassembly. RESULTS: First, a microtubule-stabilising protein, Ensconsin/MAP7,
      is inactivated in prophase as a consequence of its phosphorylation downstream of
      Cdk1/cyclin B. This leads to a reduction in interphase microtubule stability that
      may help to fuel the growth of centrosomally nucleated microtubules. The
      peripheral interphase microtubules that remain are then rapidly lost as the
      concentration of tubulin heterodimers falls following dissolution of the nuclear
      compartment boundary. Finally, we show that a failure to destabilise microtubules
      in prophase leads to the formation of microtubule clumps, which interfere with
      spindle assembly. CONCLUSIONS: This analysis highlights the importance of the
      step-wise remodelling of the microtubule cytoskeleton and the significance of
      permeabilisation of the nuclear envelope in coordinating the changes in cellular
      organisation and biochemistry that accompany mitotic entry.

PMID- 29361960
TI  - A rapid minor groove binder PCR method for distinguishing the vaccine strain
      Brucella abortus 104M.
AB  - BACKGROUND: Brucellosis is a widespread zoonotic disease caused by Gram-negative
      Brucella bacteria. Immunisation with attenuated vaccine is an effective method of
      prevention, but it can interfere with diagnosis. Live, attenuated Brucella
      abortus strain 104M has been used for the prevention of human brucellosis in
      China since 1965. However, at present, no fast and reliable method exists that
      can distinguish this strain from field strains. Single nucleotide polymorphism
      (SNP)-based assays offer a new approach for such discrimination. SNP-based minor
      groove binder (MGB) and Cycleave assays have been used for rapid identification
      of four Brucella vaccine strains (B. abortus strains S19, A19 and RB51, and B.
      melitensis Rev1). The main objective of this study was to develop a PCR assay for
      rapid and specific detection of strain 104M. RESULTS: We developed a SNP-based
      MGB PCR assay that could successfully distinguish strain 104M from 18
      representative strains of Brucella (B. abortus biovars 1, 2, 3, 4, 5, 6, 7 and 9,
      B. melitensis biovars 1, 2 and 3, B. suis biovars 1, 2, 3 and 4, B. canis, B.
      neotomae, and B. ovis), four Brucella vaccine strains (A19, S19, S2, M5), and 55
      Brucella clinical field strains. The assay gave a negative reaction with four non
      Brucella species (Escherichia coli, Pasteurella multocida, Streptococcus suis and
      Pseudomonas aeruginosa). The minimum sensitivity of the assay, evaluated using 10
      fold dilutions of chromosomal DNA, was 220 fg for the 104M strain and 76 fg for
      the single non-104M Brucella strain tested (B. abortus A19). The assay was also
      reproducible (intra- and inter-assay coefficients of variation = 0.006-0.022 and
      0.012-0.044, respectively). CONCLUSIONS: A SNP-based MGB PCR assay was developed
      that could straightforwardly and unambiguously distinguish B. abortus vaccine
      strain 104M from non-104M Brucella strains. Compared to the classical isolation
      and identification approaches of bacteriology, this real-time PCR assay has
      substantial advantages in terms of simplicity and speed, and also reduces
      potential exposure to live Brucella. The assay developed is therefore a simple,
      rapid, sensitive, and specific tool for brucellosis diagnosis and control.

PMID- 29361959
TI  - Supplemental parenteral nutrition versus usual care in critically ill adults: a
      pilot randomized controlled study.
AB  - BACKGROUND: In the critically ill, energy delivery from enteral nutrition (EN) is
      often less than the estimated energy requirement. Parenteral nutrition (PN) as a
      supplement to EN may increase energy delivery. We aimed to determine if an
      individually titrated supplemental PN strategy commenced 48-72 hours following
      ICU admission and continued for up to 7 days would increase energy delivery to
      critically ill adults compared to usual care EN delivery. METHODS: This study was
      a prospective, parallel group, phase II pilot trial conducted in six intensive
      care units in Australia and New Zealand. Mechanically ventilated adults with at
      least one organ failure and EN delivery below 80% of estimated energy requirement
      in the previous 24 hours received either a supplemental PN strategy (intervention
      group) or usual care EN delivery. EN in the usual care group could be
      supplemented with PN if EN remained insufficient after usual methods to optimise
      delivery were attempted. RESULTS: There were 100 patients included in the study
      and 99 analysed. Overall, 71% of the study population were male, with a mean (SD)
      age of 59 (17) years, Acute Physiology and Chronic Health Evaluation II score of
      18.2 (6.7) and body mass index of 29.6 (5.8) kg/m2. Significantly greater energy
      (mean (SD) 1712 (511) calories vs. 1130 (601) calories, p < 0.0001) and
      proportion of estimated energy requirement (mean (SD) 83 (25) % vs. 53 (29) %, p
      < 0.0001) from EN and/or PN was delivered to the intervention group compared to
      usual care. Delivery of protein and proportion of estimated protein requirements
      were also greater in the intervention group (mean (SD) 86 (25) g, 86 (23) %)
      compared to usual care (mean (SD) 53 (29) g, 51 (25) %, p < 0.0001). Antibiotic
      use, ICU and hospital length of stay, mortality and functional outcomes were
      similar between the two groups. CONCLUSIONS: This individually titrated
      supplemental PN strategy applied over 7 days significantly increased energy
      delivery when compared to usual care delivery. Clinical and functional outcomes
      were similar between the two patient groups. TRIAL REGISTRATION: Clinical Trial
      registry details: NCT01847534 (First registered 22 April 2013, last updated 31
      July 2016).

PMID- 29361961
TI  - An attenuated rate of leg muscle protein depletion and leg free amino acid efflux
      over time is seen in ICU long-stayers.
AB  - BACKGROUND: There is extensive documentation on skeletal muscle protein depletion
      during the initial phase of critical illness. However, for intensive care unit
      (ICU) long-stayers, objective data are very limited. In this study, we examined
      skeletal muscle protein and amino acid turnover in patients with a prolonged ICU
      stay. METHODS: Patients (n = 20) were studied serially every 8-12 days between
      days 10 and 40 of their ICU stay as long as patients stayed in the ICU. Leg
      muscle protein turnover was assessed by measurements of phenylalanine kinetics,
      for which we employed a stable isotope-labeled phenylalanine together with two
      pool and three-pool models for calculations, and results were expressed per 100
      ml of leg volume. In addition, leg muscle amino acid flux was studied. RESULTS:
      The negative leg muscle protein net balance seen on days 10-20 of the ICU stay
      disappeared by days 30-40 (p = 0.012). This was attributable mainly to an
      increase in the de novo protein synthesis rate (p = 0.007). It was accompanied by
      an attenuated efflux of free amino acids from the leg. Leg muscle protein
      breakdown rates stayed unaltered (p = 0.48), as did the efflux of 3
      methylhistidine. The arterial plasma concentrations of free amino acids did not
      change over the course of the study. CONCLUSIONS: In critically ill patients with
      sustained organ failure and in need of a prolonged ICU stay, the initial high
      rate of skeletal muscle protein depletion was attenuated over time. The
      distinction between the acute phase and a more prolonged and more stable phase
      concerning skeletal muscle protein turnover must be considered in study protocols
      as well as in clinical practice. TRIAL REGISTRATION: Australian New Zealand Trial
      Registry, ACTRN12616001012460 . Retrospectively registered on 1 August 2016.

PMID- 29361962
TI  - Evaluation of biological potential of selected species of family Poaceae from
      Bahawalpur, Pakistan.
AB  - BACKGROUND: Oxidative stress as well as bacterial and fungal infections are
      common source of diseases while plants are source of medication for curative or
      protective purposes. Hence, aim of study was to compare the pharmacological
      potential of seven grass species in two different solvents i.e. ethanol and
      acetone. METHODS: Preliminary phytochemical tests were done and antioxidant
      activities were evaluated using ELISA and their IC50 values and AAI (%) were
      recorded. ANOVA was used for statistical analyses. DNA damage protection assay
      was done using p1391Z plasmid DNA and DNA bands were analyzed. Antimicrobial
      activity was done via disc diffusion method and MIC and Activity Index were
      determined. Cytotoxic activity was carried out using the brine shrimps' assay and
      LC50 values were calculated using probit analysis program. RESULTS: Phytochemical
      studies confirmed the presence of secondary metabolites in most of the plant
      extracts. Maximum antioxidant potential was revealed in DiAEE, DiAAE (AAI- 54.54%
      and 43.24%) and DaAEE and DaAAE (AAI- 49.13% and 44.52%). However, PoAEE and
      PoAAE showed minimum antioxidant potential (AAI- 41.04% and 34.11%). SaSEE, DiAEE
      and ElIEE showed very little DNA damage protection activity. In antimicrobial
      assay, DaAEE significantly inhibited the growth of most of the microbial
      pathogens (nine microbes out of eleven tested microbes) among ethanol extracts
      while DaAAE and ImCAE showed maximum inhibition (eight microbes out of eleven
      tested microbes) among acetone plant extracts. However, PoAEE and PoAAE showed
      least antimicrobial activity. F. oxysporum and A. niger were revealed as the most
      resistant micro-organisms. ImCEA and ImCAE showed maximum cytotoxic potential
      (LC50 11.004 ppm and 7.932 ppm) as compared to the other plant extracts.
      CONCLUSION: Fodder grasses also contains a substantial phenols and flavonoids
      contents along with other secondary metabolites and, hence, possess a significant
      medicinal value. Ethanol extracts showed more therapeutic potential as compared
      to the acetone extracts. This study provides experimental evidence that the
      selected species contains such valuable natural compounds which can be used as
      medicinal drugs in future.

PMID- 29361964
TI  - Molecular xenomonitoring for post-validation surveillance of lymphatic filariasis
      in Togo: no evidence for active transmission.
AB  - BACKGROUND: Lymphatic filariasis (LF) is a mosquito-borne filarial disease
      targeted for elimination by the year 2020. The Republic of Togo undertook mass
      treatment of entire endemic communities from 2000 to 2009 to eliminate the
      transmission of the disease and is currently the first sub-Saharan African
      country to be validated by WHO for the elimination of LF as a public health
      problem. However, post-validation surveillance activities are required to ensure
      the gains achieved are sustained. This survey assessed the mosquito vectors of
      the disease and determined the presence of infection in these vectors, testing
      the hypothesis that transmission has already been interrupted in Togo. METHOD:
      Mosquitoes were collected from 37 villages located in three districts in one of
      four evaluation units in the country. In each district, 30 villages were selected
      based on probability proportionate to size; eight villages (including one of the
      30 villages already selected) where microfilaremia-positive cases had been
      identified during post-treatment surveillance activities were intentionally
      sampled. Mosquitoes were collected using pyrethrum spray collections (PSC) in
      households randomly selected in all villages for five months. In the purposefully
      selected communities, mosquitoes were also collected using human landing
      collections (HLC) and exit traps (ET). Collected mosquitoes were identified
      morphologically, and the identification of Wuchereria bancrofti DNA in the
      mosquitoes was based on the pool screening method, using the LAMP assay. RESULTS:
      A total of 15,539 mosquitoes were collected during the study. Anopheles gambiae
      (72.6%) was the predominant LF vector collected using PSC. Pool screen analysis
      of 9191 An. gambiae in 629 pools revealed no mosquitoes infected with W.
      bancrofti (0%; CI: 0-0.021). CONCLUSIONS: These results confirm the findings of
      epidemiological transmission assessment surveys conducted in 2012 and 2015, which
      demonstrated the absence of LF transmission in Togo. The challenges of
      implementing molecular xenomonitoring are further discussed.

PMID- 29361963
TI  - Diagnostic tools in childhood malaria.
AB  - Every year, millions of people are burdened with malaria. An estimated 429,000
      casualties were reported in 2015, with the majority made up of children under
      five years old. Early and accurate diagnosis of malaria is of paramount
      importance to ensure appropriate administration of treatment. This minimizes the
      risk of parasite resistance development, reduces drug wastage and unnecessary
      adverse reaction to antimalarial drugs. Malaria diagnostic tools have expanded
      beyond the conventional microscopic examination of Giemsa-stained blood films.
      Contemporary and innovative techniques have emerged, mainly the rapid diagnostic
      tests (RDT) and other molecular diagnostic methods such as PCR, qPCR and loop
      mediated isothermal amplification (LAMP). Even microscopic diagnosis has gone
      through a paradigm shift with the development of new techniques such as the
      quantitative buffy coat (QBC) method and the Partec rapid malaria test. This
      review explores the different diagnostic tools available for childhood malaria,
      each with their characteristic strengths and limitations. These tools play an
      important role in making an accurate malaria diagnosis to ensure that the use of
      anti-malaria are rationalized and that presumptive diagnosis would only be a
      thing of the past.

PMID- 29361965
TI  - Eight-year trend analysis of malaria prevalence in Kombolcha, South Wollo, north
      central Ethiopia: a retrospective study.
AB  - BACKGROUND: Malaria is one of the most serious public health problems in the
      world, and is a major public health problem in Ethiopia. Over the past years, the
      disease has been consistently reported as the first leading cause of outpatient
      visits, hospitalization and death in health facilities across the country. This
      study aimed to assess malaria prevalence trend in the Kombolcha Health Centre.
      METHODS: A retrospective study was carried out in the Kombolcha Health Centre,
      north-central Ethiopia. Malaria cases reported from 2009 to 2016 were carefully
      reviewed from the laboratory record books. Interventions that had been taken in
      each year were collected from the district health bureau and head of Kombolcha
      Health Centre using checklists. RESULTS: A total of 27,492 blood films were
      examined from malaria-suspected patients in the Kombolcha Health Centre from 2009
      to 2016. Malaria was confirmed and reported in 2066 (7.52%) of the examined blood
      films with 258 mean annual cases of. Minimum and maximum cases were reported in
      2009 and 2010, respectively. Plasmodium falciparum and P. vivax accounted 60.2%
      and 35.5% of the cases, respectively. Male patients were more affected (n = 1407;
      68.1%) than female ones (n = 659; 31.89%). The highest malaria prevalence (n =
      1440; 69.69%) was seen in the 15-45 years age group, followed by those 5-14 years
      old (n = 303; 14.67%), and finally patients under five years old (n = 217;
      10.5%). Malaria cases were at a peak in spring and reduced in the winter season.
      CONCLUSION: Although the current malaria control strategies are effective in
      decreasing the morbidity and mortality, malaria is still among major public
      health problems in Ethiopia. Plasmodium falciparum is the dominant species in the
      study area. However, in recent years P. vivax cases are increasing, indicating
      that attention should also be given to this species. The efficacy of chloroquine
      for P. vivax should be evaluated in the study area. Control activities should be
      continued and scale up.

PMID- 29361966
TI  - The experiences of people with diabetes-related lower limb amputation at the
      Komfo Anokye Teaching Hospital (KATH) in Ghana.
AB  - OBJECTIVE: Lower limb amputation not only causes major disfigurement, but renders
      people less mobile and at risk of loss of independence. Yet with appropriate
      rehabilitation, many people can learn to walk or function again and live high
      quality lives. This study sought to explore the experiences of patients with
      diabetes-related lower limb amputation at the Komfo Anokye Teaching Hospital. An
      exploratory study design was adopted using a qualitative approach and a purposive
      sampling to select 10 participants for the study. A semi-structured interview
      guide was used with an in-depth face-to-face interview. The interview was tape
      recorded with an audio recorder while notes were taken in addition to the audio
      recording. RESULTS: There were varying degrees of experiences ranging from
      physical as well as psychological and economic challenges. Amputees had to cope
      with playing entirely new roles after the amputation. They also experienced some
      economic challenges which were as a result of their inability to work. Some of
      the amputees consoled themselves with the fact that, despite their condition,
      they were better than other people. Others believed that whatever happened was
      Gods doing and nothing could be done about it. This self-consolation and the
      belief in God helped them to cope.

PMID- 29361967
TI  - The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep,
      cognition, thyroid function, and cardiovascular health independent of weight
      loss: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Many physiological health benefits observed after following a
      ketogenic diet (KD) can be attributed to the associated weight loss. The KD has
      become more prominent as a popular health choice, not only in obese/overweight
      individuals, but also in healthy adults. The study aims to determine the effects
      of a KD, independent of weight loss, on various aspects of physiological health
      including: sleep, thyroid function, cognition, and cardio-metabolic health. The
      study will also aim to determine whether a change in basal metabolic rate may be
      associated with any changes observed. METHODS: Twenty healthy men and women
      between 18 and 50 years of age will take part in this study. In a randomized
      controlled, cross-over design, participants will follow two isocaloric diets: a
      high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15%
      CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of
      3 weeks, with a 1-week washout period in between. Before and after each diet,
      participants will be assessed for sleep quality, cognitive function, thyroid
      function, and basal metabolic rate. A blood sample will also be taken for the
      measurement of cardio-metabolic and immune markers. DISCUSSION: The present study
      will help in understanding the potential effects of a KD on aspects of
      physiological health in healthy adults, without the confounding factor of weight
      loss. The study aims to fill a significant void in the academic literature with
      regards to the benefits and/or risks of a KD in a healthy population, but will
      also explore whether diet-related metabolic changes may be responsible for the
      changes observed in physiological health. TRIAL REGISTRATION: Pan African
      Clinical Trial Registry ( www.pactr.org ), trial number: PACTR201707002406306 .
      Registered on 20 July 2017.

PMID- 29361968
TI  - An obesity-associated gut microbiome reprograms the intestinal epigenome and
      leads to altered colonic gene expression.
AB  - BACKGROUND: The gut microbiome, a key constituent of the colonic environment, has
      been implicated as an important modulator of human health. The eukaryotic
      epigenome is postulated to respond to environmental stimuli through alterations
      in chromatin features and, ultimately, gene expression. How the host mediates
      epigenomic responses to gut microbiota is an emerging area of interest. Here, we
      profile the gut microbiome and chromatin characteristics in colon epithelium from
      mice fed either an obesogenic or control diet, followed by an analysis of the
      resultant changes in gene expression. RESULTS: The obesogenic diet shapes the
      microbiome prior to the development of obesity, leading to altered bacterial
      metabolite production which predisposes the host to obesity. This microbiota-diet
      interaction leads to changes in histone modification at active enhancers that are
      enriched for binding sites for signal responsive transcription factors. These
      alterations of histone methylation and acetylation are associated with signaling
      pathways integral to the development of colon cancer. The transplantation of
      obesogenic diet-conditioned microbiota into germ free mice, combined with an
      obesogenic diet, recapitulates the features of the long-term diet regimen. The
      diet/microbiome-dependent changes are reflected in both the composition of the
      recipient animals' microbiome as well as in the set of transcription factor
      motifs identified at diet-influenced enhancers. CONCLUSIONS: These findings
      suggest that the gut microbiome, under specific dietary exposures, stimulates a
      reprogramming of the enhancer landscape in the colon, with downstream effects on
      transcription factors. These chromatin changes may be associated with those seen
      during colon cancer development.

PMID- 29361970
TI  - Psychometric properties of a Thai version internet addiction test.
AB  - OBJECTIVE: The aim was to assess the reliability and validity of a Thai version
      internet addiction test. RESULTS: Cronbach's alpha for the Thai version of the
      internet addiction test was 0.89. A three-factor model showed the best fit with
      the data for the whole sample, whereas the hypothesized six-factor model, as well
      as a unidimensional model of the internet addiction test, failed to demonstrate
      acceptable fit with the data. Three factors, namely functional impairment,
      withdrawal symptoms and loss of control, exhibited Cronbach's alphas of 0.81,
      0.81, and 0.70, respectively. Item 4, 'to form new relationships with online
      users', yielded the lowest loading coefficient of all items. Positive
      correlations between the internet addiction test and UCLA loneliness scores were
      found. The Thai version of the internet addiction test was considered reliable
      and valid, and has sufficient unidimensionality to calculate for total score in
      screening for excessive internet use.

PMID- 29361969
TI  - Medical student attitudes towards older people: a critical review of quantitative
      measures.
AB  - OBJECTIVES: Further research into medical student attitudes towards older people
      is important, and requires accurate and detailed evaluative methodology. The two
      objectives for this paper are: (1) From the literature, to critically review
      instruments of measure for medical student attitudes towards older people, and
      (2) To recommend the most appropriate quantitative instrument for future research
      into medical student attitudes towards older people. RESULTS: A SCOPUS and Ovid
      cross search was performed using the keywords Attitude and medical student and
      aged or older or elderly. This search was supplemented by manual searching,
      guided by citations in articles identified by the initial literature search,
      using the SCOPUS and PubMed databases. International studies quantifying medical
      student attitudes have demonstrated neutral to positive attitudes towards older
      people, using various instruments. The most commonly used instruments are the
      Ageing Semantic Differential (ASD) and the University of California Los Angeles
      Geriatric Attitudes Scale, with several other measures occasionally used. All
      instruments used to date have inherent weaknesses. A reliable and valid
      instrument with which to quantify modern medical student attitudes towards older
      people has not yet been developed. Adaptation of the ASD for contemporary usage
      is recommended.

PMID- 29361971
TI  - Multiflora rose invasion amplifies prevalence of Lyme disease pathogen, but not
      necessarily Lyme disease risk.
AB  - BACKGROUND: Forests in urban landscapes differ from their rural counterparts in
      ways that may alter vector-borne disease dynamics. In urban forest fragments,
      tick-borne pathogen prevalence is not well characterized; mitigating disease risk
      in densely-populated urban landscapes requires understanding ecological factors
      that affect pathogen prevalence. We trapped blacklegged tick (Ixodes scapularis)
      nymphs in urban forest fragments on the East Coast of the United States and used
      multiplex real-time PCR assays to quantify the prevalence of four zoonotic, tick
      borne pathogens. We used Bayesian logistic regression and WAIC model selection to
      understand how vegetation, habitat, and landscape features of urban forests
      relate to the prevalence of B. burgdorferi (the causative agent of Lyme disease)
      among blacklegged ticks. RESULTS: In the 258 nymphs tested, we detected Borrelia
      burgdorferi (11.2% of ticks), Borrelia miyamotoi (0.8%) and Anaplasma
      phagocytophilum (1.9%), but we did not find Babesia microti (0%). Ticks collected
      from forests invaded by non-native multiflora rose (Rosa multiflora) had greater
      B. burgdorferi infection rates (mean = 15.9%) than ticks collected from uninvaded
      forests (mean = 7.9%). Overall, B. burgdorferi prevalence among ticks was
      positively related to habitat features (e.g. coarse woody debris and total
      understory cover) favorable for competent reservoir host species. CONCLUSIONS:
      Understory structure provided by non-native, invasive shrubs appears to aggregate
      ticks and reservoir hosts, increasing opportunities for pathogen transmission.
      However, when we consider pathogen prevalence among nymphs in context with
      relative abundance of questing nymphs, invasive plants do not necessarily
      increase disease risk. Although pathogen prevalence is greater among ticks in
      invaded forests, the probability of encountering an infected tick remains greater
      in uninvaded forests characterized by thick litter layers, sparse understories,
      and relatively greater questing tick abundance in urban landscapes.

PMID- 29361972
TI  - Considerations for skin carcinogenesis experiments using inducible transgenic
      mouse models.
AB  - OBJECTIVE: This study was designed to estimate the percentage of non-malignant
      skin tumours (papillomas) progressing to malignant squamous cell carcinomas
      (SCCs) in a carcinogenesis study using established transgenic mouse models. In
      our skin cancer model, we conditionally induced oncogenic point mutant alleles of
      p53 and k-ras in undifferentiated, basal cells of the epidermis. RESULTS: Upon
      activation of the transgenes through administration of tamoxifen, the vast
      majority of mice (> 80%) developed skin papillomas, yet primarily around the
      mouth. Since these tumours hindered the mice eating, they rapidly lost weight and
      needed to be culled before the papillomas progressed to SCCs. The mouth
      papillomas formed regardless of the route of application, including
      intraperitoneal injections, local application to the back skin, or subcutaneous
      insertion of a tamoxifen pellet. Implantation of a slow releasing tamoxifen
      pellet into 18 mice consistently led to papilloma formation, of which only one
      progressed to a malignant SCC. Thus, the challenges for skin carcinogenesis
      studies using this particular cancer mouse model are low conversion rates of
      papillomas to SCCs and high frequencies of mouth papilloma formation.

PMID- 29361973
TI  - Celiac disease associated with aplastic anemia in a 6-year-old girl: a case
      report and review of the literature.
AB  - BACKGROUND: Celiac disease may present with hematological abnormalities including
      long-standing anemia. Both aplastic anemia and celiac disease have a similar
      underlying autoimmune process but an association between the two is seldom
      reported. There have only been three pediatric cases reporting this association
      and this case is the first reported in a female pediatric patient. CASE
      PRESENTATION: We report a case of 6-year-old South Asian girl presenting with
      bruises, petechiae, and recent history of loose stools. On evaluation, she was
      diagnosed as having celiac disease and was put on a gluten-free diet and further
      investigations including bone marrow biopsy revealed pancytopenia. She was
      managed with packed red cells, platelets, and diet restrictions and had improving
      platelet counts over yearly follow ups. Her parents were counseled regarding the
      need for bone marrow transplant. CONCLUSIONS: This is the fourth case report
      suggesting an association between celiac disease and aplastic anemia in the
      pediatric population and this association could be more common than expected.
      Timely intervention of either celiac disease through strict gluten-free diet or
      aplastic anemia through immunosuppressive therapy could potentially reduce the
      risk for other autoimmune conditions. We can see that all four pediatric cases
      reported with this potential association are from South East Asia and hence
      larger studies would be prudent to explore this association.

PMID- 29361974
TI  - Localization and dimer stability of a newly identified microbial rhodopsin from a
      polar, non-motile green algae.
AB  - OBJECTIVE: The eukaryotic plasma membrane localized light-gated proton-pumping
      rhodopsins possesses great optogenetic applications for repolarization
      (silencing) of the neuronal activity simply by light illumination. Very few
      plasma membrane localized proton-pumping rhodopsins of a eukaryotic origin are
      known that have optogenetic potential. Our objective was to identify and
      characterize microbial rhodopsin of an eukaryotic origin that expresses on plasma
      membrane. The plasma membrane localized light-gated proton pump of an eukaryotic
      origin hold great promise to be used as an optogenetic tools for the
      neurobiology. RESULTS: Here, we had characterized the cellular expression and
      membrane localization of a new rhodopsin in Antarctican algae Coccomyxa
      subellipsoidea. It is the first algal ion pumping rhodopsin that localizes to the
      plasma membrane of the eukaryotic cells. Coccomyxa subellipsoidea rhodopsin
      exists in the monomeric and dimeric state both the in vivo and in vitro. The
      dimeric form of the Coccomyxa subellipsoidea rhodopsin is resistant to heat and
      detergent denaturants.

PMID- 29361975
TI  - Anxiety and the development and maintenance of anorexia nervosa: protocol for a
      systematic review.
AB  - BACKGROUND: Several aetiological models of anorexia nervosa (AN) hold non
      eating/weight-gain-related anxiety as a factor relevant to the onset and
      maintenance of the disorder. Longitudinal studies that allow assessment of this
      hypothesis have been conducted; however, the evidence has not yet been aggregated
      in a systematic manner. The proposed study will systematically review articles
      describing prospective investigations of the relationship between anxiety and AN
      development or maintenance, with the aim of providing a balanced summary of
      current understanding and identifying areas for further research. METHODS/DESIGN:
      Electronic databases will be searched for articles investigating the longitudinal
      influence of non-eating/weight-gain-related anxiety (anxiety disorders and trait
      anxiety) on the development/maintenance of AN. References of eligible articles
      will be searched to ensure the identification of all relevant studies. Two
      independent reviewers will complete the title and abstract, and full-text,
      screening, with a third independent reviewer resolving any conflicts at each
      stage. A systematic review will be completed, and the quality of the included
      studies, as well as the strength of the body of evidence generated, will be
      assessed and reported. DISCUSSION: Although there are limitations to the present
      review, understanding the current evidence for the role of non-eating/weight-gain
      related anxiety in AN can direct future research that may ensure accurate
      aetiological models of AN and effective treatments. SYSTEMATIC REVIEW
      REGISTRATION: The study is registered on PROSPERO under the reference number
      CRD42017069644.

PMID- 29361976
TI  - Evaluation of tumor volume reduction of nasal carcinomas versus sarcomas in dogs
      treated with definitive fractionated megavoltage radiation: 15 cases (2010-2016).
AB  - OBJECTIVE: Local control is a major challenge in treating canine nasal tumors,
      and cytoreduction following radiation therapy has been recommended to extend
      survival and to delay local recurrence. Our objective was to compare the effect
      of definitive radiotherapy on the tumor volume of intranasal carcinomas compared
      to sarcomas. We evaluated 15 dogs that received radiotherapy within 1 month of
      initial CT scan, and post radiation CT scans performed within 3 months of
      completing full course definitive megavoltage radiation. Tumor reduction volume
      based on CT scans were obtained and compared between carcinoma and sarcoma
      groups. RESULTS: The following tumor types were treated; carcinoma (8/15),
      sarcoma (7/15). The mean nasal tumor size before radiation therapy was 24.5 cm3
      and tumor size after radiation therapy was 13.5 cm3 resulting in a mean reduction
      of 55.1% reduction in tumor size for both carcinomas and sarcomas. The carcinoma
      group displayed a volume reduction of 67.1% (SD +/- 16.9) and the sarcoma group
      displayed a volume reduction of 21.3% (SD +/- 39.7). Within the study period
      carcinomas were more responsive in the reduction of volume than sarcomas with
      fractionated megavoltage radiation.

PMID- 29361977
TI  - Climate change jeopardizes the persistence of freshwater zooplankton by reducing
      both habitat suitability and demographic resilience.
AB  - BACKGROUND: Higher temperatures and increased environmental variability under
      climate change could jeopardize the persistence of species. Organisms that rely
      on short windows of rainfall to complete their life-cycles, like desert annual
      plants or temporary pool animals, may be particularly at risk. Although some
      could tolerate environmental changes by building-up banks of propagules (seeds or
      eggs) that buffer against catastrophes, climate change will threaten this
      resilience mechanism if higher temperatures reduce propagule survival. Using a
      crustacean model species from temporary waters, we quantified experimentally the
      survival and dormancy of propagules under anticipated climate change and used
      these demographic parameters to simulate long term population dynamics. RESULTS:
      By exposing propagules to present-day and projected daily temperature cycles in
      an 8 month laboratory experiment, we showed how increased temperatures reduce
      survival rates in the propagule bank. Integrating these reduced survival rates
      into population models demonstrated the inability of the bank to maintain
      populations; thereby exacerbating extinction risk caused by shortened growing
      seasons. CONCLUSIONS: Overall, our study demonstrates that climate change could
      threaten the persistence of populations by both reducing habitat suitability and
      eroding life-history strategies that support demographic resilience.

PMID- 29361978
TI  - Use of DAVID algorithms for clustering custom annotated gene lists in a non-model
      organism, rainbow trout.
AB  - OBJECTIVE: The DAVID gene functional classification tool requires adaptations for
      use in non-model species and there is little available information to guide
      selection of a kappa score. Our objective was to develop an R-script that allows
      custom gene identifiers and novel annotation information to be incorporated into
      analyses, then use such data to evaluate the number of differentially expressed
      genes (DEGs) in a comparison based on kappa score selection. RESULTS: Using an R
      script we developed and multiple data sets ranging from 555 to 3340 annotated
      DEGs from a study in rainbow trout, we found the percentage of DEGs harbored
      within a module and the number of genes shared among multiple modules decreased
      with increasing kappa score regardless of the number of DEGs in the comparison.
      The number of genes in enriched modules peaked at a kappa score of 0.5 for the
      comparisons with 3340 and 1313 DEGs and 0.3 for 555 DEGs. The number of genes
      harbored within enriched modules generally decreased with increasing kappa score;
      however, this was affected by whether the largest modules were significantly
      enriched. Large non-enriched modules can be reanalyzed using a higher kappa score
      resulting in some of the genes clustering in smaller enriched modules.

PMID- 29361979
TI  - Enhanced differentiation of human pluripotent stem cells into pancreatic
      progenitors co-expressing PDX1 and NKX6.1.
AB  - BACKGROUND: Pancreatic progenitors (PPs) co-expressing the two transcription
      factors (TFs) PDX1 and NKX6.1 are recognized as the indispensable precursors of
      functional pancreatic beta cells. Here, we aimed to establish an efficient
      protocol for maximizing generation of PDX1+/NKX6.1+ PPs from human pluripotent
      stem cells (hPSCs). METHODS: In order to enhance the PDX1+/NKX6.1+ population, we
      manipulated in vitro culture conditions during differentiation by dissociating
      densely formed endodermal cells and re-plating them at different densities. These
      dissociated cells were subjected to an augmented duration of retinoid and
      fibroblast growth factor (FGF)10 signaling to induce higher PDX1 and NKX6.1
      expression. RESULTS: Our optimized protocol dramatically increased the expression
      of NKX6.1, leading to an increase in the proportion of PDX1+/NKX6.1+ progenitors
      (~90%) in monolayer, higher than the previously published protocols, as well as
      upregulated key TFs controlling pancreatic development. The improved efficiency
      of pancreatic differentiation was complemented by an inhibited hepatic
      specification and an increased proliferation of NKX6.1+ cells. Interestingly, we
      were able to enrich a novel PDX1-/NKX6.1+ population by manipulating the re
      plating density; these oriented themselves in three-dimensional clusters. Further
      differentiation validated the ability of our PDX1+/NKX6.1+ progenitors to
      generate NGN3+ endocrine progenitors. CONCLUSIONS: We provide a novel technique
      that facilitates appropriate cellular rearrangement in monolayer culture to yield
      a high proportion of PDX1+/NKX6.1+ PPs with an elevated self-replicating
      capacity, thereby aiding scalable production of functional beta cells from hPSCs
      in vitro. Our innovative method also enriches a novel NKX6.1+/PDX1- population,
      with characteristics of proposed endocrine precursors, allowing further studies
      on deciphering routes to beta-cell development.

PMID- 29361980
TI  - Outcomes of children aged 6-59 months with severe acute malnutrition at the GADO
      Outpatient Therapeutic Center in Cameroon.
AB  - OBJECTIVE: We aimed to assess outcomes [rates of recovery, default, case
      fatality; rate of weight gain and rate of Mean Upper Arm Circumference (MUAC)
      gain] of children aged 6-59 months with severe acute malnutrition (SAM) at the
      Outpatient Therapeutic Center at Gado Refugee Camp, Cameroon, in relation to
      international standards. We retrospectively analysed files of 254 children with
      SAM aged 6-59 months admitted from April 2015 to August 2016. RESULTS: 72.8% got
      discharged as recovered, 0.8% died and none defaulted. 26.8% got referred to
      stabilization center, mostly for poor weight gain (44.1%). Mean rate of weight
      gain was 4.4 g/kg/day and MUAC gain 0.3 mm/cm/day; median duration of treatment
      44.5 days. Amongst those with marasmus, kwashiorkor and marasmic kwashiorkor,
      median duration of stay was 48, 24.5 and 36.3 days (p = 0.002); recovery rates
      were similar 73, 71.4, 71.4% respectively (p = 0.7); Median rates of weight gain,
      4.4, 6.7 and 8.1 g/kg/day (p = 0.05). 49 children had been incorrectly diagnosed
      and treated as SAM. International Standards were met in terms of case fatality
      rate and default rate but not rates of recovery and weight gain. Separate gender
      charts must be used to calculate weight for height z scores as combined charts
      cause significant errors.

PMID- 29361981
TI  - Intraoperative Brief Electrical Stimulation of the Spinal Accessory Nerve (BEST
      SPIN) for prevention of shoulder dysfunction after oncologic neck dissection: a
      double-blinded, randomized controlled trial.
AB  - BACKGROUND: Shoulder dysfunction is common after neck dissection for head and
      neck cancer (HNC). Brief electrical stimulation (BES) is a novel technique that
      has been shown to enhance neuronal regeneration after nerve injury by modulating
      the brain-derived neurotrophic growth factor (BDNF) pathways. The objective of
      this study was to evaluate the effect of BES on postoperative shoulder function
      following oncologic neck dissection. METHODS: Adult participants with a new
      diagnosis of HNC undergoing Level IIb +/- V neck dissection were recruited. Those
      in the treatment group received intraoperative BES applied to the spinal
      accessory nerve (SAN) after completion of neck dissection for 60 min of
      continuous 20 Hz stimulation at 3-5 V of 0.1 msec balanced biphasic pulses, while
      those in the control group received no stimulation (NS). The primary outcome
      measured was the Constant-Murley Shoulder (CMS) Score, comparing changes from
      baseline to 12 months post-neck dissection. Secondary outcomes included the
      change in the Neck Dissection Impairment Index (DeltaNDII) score and the change
      in compound muscle action potential amplitude (DeltaCMAP) over the same period.
      RESULTS: Fifty-four patients were randomized to the treatment or control group
      with a 1:1 allocation scheme. No differences in demographics, tumor
      characteristics, or neck dissection types were found between groups.
      Significantly lower DeltaCMS scores were observed in the BES group at 12 months,
      indicating better preservation of shoulder function (p = 0.007). Only four in the
      BES group compared to 17 patients in the NS groups saw decreases greater than the
      minimally important clinical difference (MICD) of the CMS (p = 0.023). However,
      NDII scores (p = 0.089) and CMAP amplitudes (p = 0.067) between the groups did
      not reach statistical significance at 12 months. BES participants with Level IIb
      + V neck dissections had significantly better DeltaCMS and DeltaCMAP scores at 12
      months (p = 0.048 and p = 0.025, respectively). CONCLUSIONS: Application of BES
      to the SAN may help reduce impaired shoulder function in patients undergoing
      oncologic neck dissection, and may be considered a viable adjunct to functional
      rehabilitation therapies. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02268344 ,
      October 17, 2014).

PMID- 29361982
TI  - Development of a complex intervention for people with chronic pain after knee
      replacement: the STAR care pathway.
AB  - BACKGROUND: Approximately 20% of people who have total knee replacement
      experience chronic pain afterwards, but there is little evidence about effective
      interventions for managing this type of pain. This article describes the
      systematic development and refinement of a complex intervention for people with
      chronic pain after knee replacement. The intervention is a care pathway involving
      an assessment clinic and onward referral, with telephone follow-up as required.
      In the design of this multistage study, we chose to focus on ensuring that the
      intervention was deliverable, implementable and acceptable. METHODS: In line with
      the UK Medical Research Council's recommendations for comprehensive development
      of complex interventions, multiple phases of work were undertaken. Following on
      from initial development work to design the intervention, the draft intervention
      content was refined through consensus questionnaires with 22 health professionals
      and discussion at meetings with 18 healthcare professionals. Testing of
      intervention delivery and acceptability to patients was undertaken by two health
      professionals delivering the assessment clinic to ten patients. Views about
      future implementation within the context of a randomised trial were evaluated
      through a questionnaire based on the Normalisation Measure Development (NoMAD)
      instrument with ten health professional stakeholders. RESULTS: Consensus work
      with health professionals ensured the components of the intervention were
      appropriate and informed a number of substantive changes to improve the
      intervention. Testing of intervention delivery identified a number of logistical
      issues that were then addressed in the development of a comprehensive
      intervention training manual. Engagement with stakeholders indicated that the
      intervention could be successfully implemented in a clinical setting for
      evaluation in a randomised trial. CONCLUSIONS: This work has informed the
      development and refinement of a complex intervention for people with chronic pain
      after knee replacement. The next stage is to evaluate the clinical and cost
      effectiveness of the STAR care pathway in a multicentre randomised trial.

PMID- 29361983
TI  - Cardiac computed tomography in patients with symptomatic new-onset atrial
      fibrillation, rule-out acute coronary syndrome, but with intermediate pretest
      probability for coronary artery disease admitted to a chest pain unit.
AB  - BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) may be
      encountered coincidently in a large portion of patients. However, data on
      coronary artery calcium burden in such patients are lacking. Thus, we sought to
      determine the value of cardiac computed tomography (CCT) in patients presenting
      with new-onset AF associated with an intermediate pretest probability for CAD
      admitted to a chest pain unit (CPU). METHODS: Calcium scores (CS) of 73 new
      onset, symptomatic AF subjects without typical clinical, electrocardiographic, or
      laboratory signs of acute coronary syndrome (ACS) admitted to our CPU were
      analyzed. In addition, results from computed tomography angiography (CTA) were
      related to coronary angiography findings whenever available. RESULTS: Calcium
      scores of zero were found in 25%. Median Agatston score was 77 (interquartile
      range: 1-270) with gender- and territory-specific dispersal. CS scores above
      average were present in about 50%, high (> 400)-to-very high (> 1000) CS scores
      were found in 22%. Overall percentile ranking showed a relative accordance to the
      reference percentile distribution. Additional CTA was performed in 47%, revealing
      stenoses in 12%. Coronary angiography was performed in 22% and resulted in
      coronary intervention or surgical revascularization in 7%. On univariate
      analysis, CS > 50th percentile failed to serve as an independent determinant of
      significant stenosis during catheterization. CONCLUSIONS: Within a CPU setting,
      relevant CAD was excluded or confirmed in almost 50%, the latter with a high
      proportion of coronary angiographies and subsequent coronary interventions,
      underlining the diagnostic value of CCT in symptomatic, non-ACS, new-onset AF
      patients when admitted to a CPU.

PMID- 29361984
TI  - Changes in biodistribution on 68Ga-DOTA-Octreotate PET/CT after long acting
      somatostatin analogue therapy in neuroendocrine tumour patients may result in
      pseudoprogression.
AB  - BACKGROUND: To evaluate the effects of long-acting somatostatin analogue (SSA)
      therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic
      sites in neuroendocrine tumour (NET) patients. METHODS: Twenty-one patients who
      underwent GaTate PET/CT before and after commencement of SSA therapy were
      reviewed. Maximum standardized uptake values (SUVmax) were measured in normal
      organs. Changes in uptake of 49 metastatic lesions in 12 patients with stable
      disease were also compared. Serum chromogranin-A (CgA) levels were available for
      correlation between scans in 17/21 patients. RESULTS: Mean thyroid, spleen and
      liver SUVmax decreased significantly following SSA therapy from a baseline of 5.9
      to 3.5, 30.3 to 23.1 and 10.3 to 8.0, respectively (p = < 0.0001 for all).
      Pituitary SUVmax increased from 10.2 to 11.0 (p = 0.004) whereas adrenal and
      salivary gland SUVmax did not change. Tumour SUVmax increased in 7 of 12 patients
      with stable disease; CgA was stable or decreasing in 5 of these patients. 30/49
      (61%) metastatic lesions had an increase in SUVmax and lesion-to-liver uptake
      ratio increased in 40/49 (82%) following SSA therapy. CONCLUSION: Long-acting SSA
      therapy decreases GaTate uptake in the thyroid, spleen and liver but in most
      cases increases intensity of uptake within metastases. This has significant
      implications for interpretation of GaTate PET/CT following commencement of
      therapy as increased intensity alone may not represent true progression. Our
      findings also suggest pre-dosing with SSA prior to PRRT may enable higher doses
      to be delivered to tumour whilst decreasing dose to normal tissues.

PMID- 29361986
TI  - Perceived causes and risk factors of Buruli ulcer among patients at Agogo
      Presbyterian hospital in Ashanti Region of Ghana.
AB  - OBJECTIVE: The incidence of Buruli ulcer has been recorded in about 30 countries
      globally and Africa seems to be the most affected area. The study sought to
      determine perceived causes and risk factors of Buruli ulcer among patients who
      visit the Agogo hospital in Asante-Akim North District in the Ashanti region of
      Ghana. A descriptive study design was adopted using a simple random sampling
      technique to select 400 patients attending The Presbyterian Hospital at Agogo.
      Data was collected using a structured questionnaire and analysed using SPSS
      version 16.0. RESULTS: Buruli ulcer was perceived as a disease caused by
      witchcraft (38%), enemies (15%), as well as not pouring libation or praying
      (16%). Also, increased appetite (30%), oedema or swelling on the skin (29%) and
      over weight (23%) was perceived as signs and symptoms of Buruli ulcer and a
      section of the respondents (53%) did not know any risk factor. The age of
      respondents, gender and level of education were found to determine knowledge of
      Buruli ulcer (P <= .05). Public Educations and campaigns should focus on causes
      and risk factors to ensure that there is adequate knowledge among the general
      public on Buruli ulcer.

PMID- 29361985
TI  - Inherited factors contribute to an inverse association between preeclampsia and
      breast cancer.
AB  - BACKGROUND: Preeclampsia is frequently linked to reduced breast cancer risk.
      However, little is known regarding the underlying genetic association and the
      association between preeclampsia and mammographic density. METHODS: This study
      estimates the incidence rate ratios (IRRs) of breast cancer in patients with
      preeclampsia, when compared to women without preeclampsia, using Poisson
      regression models in two cohorts of pregnant women: a Swedish nationwide cohort
      (n = 1,337,934, 1973-2011) and the Karolinska Mammography Project for Risk
      Prediction of Breast Cancer (KARMA, n = 55,044, 1958-2015). To identify the
      genetic association between preeclampsia and breast cancer, we used logistic
      regression models to calculate the odds ratios (ORs) of preeclampsia in sisters
      of breast cancer patients, and in women with different percentiles of breast
      cancer polygenic risk scores (PRS). Linear regression models were used to
      estimate the mammographic density by preeclampsia status in the KARMA cohort.
      RESULTS: A decreased risk of breast cancer was observed among patients with
      preeclampsia in both the nationwide (IRR = 0.90, 95% CI = 0.85; 0.96) and KARMA
      cohorts (IRR = 0.75, 95% CI = 0.61; 0.93). Women with high breast cancer PRS and
      sisters of breast cancer patients had a lower risk of preeclampsia (OR = 0.89,
      95% CI = 0.83; 0.96). Mammographic density was lower in women with preeclampsia
      compared to women without preeclampsia (-2.04%, 95% CI = -2.65; -1.43).
      Additionally, among sisters in the KARMA cohort (N = 3500), density was lower in
      sisters of patients with preeclampsia compared to sisters of women without
      preeclampsia (-2.76%, 95% CI = -4.96; -0.56). CONCLUSION: Preeclampsia is
      associated with reduced risk of breast cancer and mammographic density. Inherited
      factors contribute to this inverse association.

PMID- 29361987
TI  - Tracking hematopoietic precursor division ex vivo in real time.
AB  - BACKGROUND: Deciphering molecular mechanisms underlying the division of
      hematopoietic stem cells (HSCs) and malignant precursors would improve our
      understanding of the basis of stem cell-fate decisions and oncogenic
      transformation. METHODS: Using a novel reporter of hematopoietic precursor, Evi1
      GFP, we tracked the division of hematopoietic precursors in culture in real time.
      RESULTS: First, we confirmed that Evi1-GFP is a faithful reporter of HSC activity
      and identified three dividing patterns of HSCs: symmetric renewal, symmetric
      differentiation, and asymmetric division. Moreover, we found that the cytokine
      and growth factor combination (STIF) promotes symmetric renewal, whereas OP9
      stromal cells balance symmetric renewal and differentiation of HSCs ex vivo.
      Interestingly, we found that Tet2 knockout HSCs underwent more symmetric
      differentiation in culture compared with the wild-type control. Intriguingly, OP9
      stromal cells reverse the phenotype of Tet2 knockout HSCs ex vivo. Furthermore,
      we demonstrated that Tet2 -/- ;Flt3ITD acute myeloid leukemia (AML) precursors
      primarily underwent symmetric renewal divisions in culture. Mechanistically, we
      demonstrated that inhibiting DNA methylation can reverse the aberrant division
      phenotypes of Tet2 -/- and Tet2 -/- ;FLT3ITD precursors, suggesting that abnormal
      DNA methylation plays an important role in controlling (pre-)leukemic precursor
      fate decision ex vivo. CONCLUSIONS: Our study exploited a new system to explore
      the molecular mechanisms of the regulation of benign and malignant hematopoietic
      precursor division ex vivo. The knowledge learned from these studies will provide
      new insights into the molecular mechanisms of HSC fate decision and
      leukemogenesis.

PMID- 29361988
TI  - Black tea aroma inhibited increase of salivary chromogranin-A after arithmetic
      tasks.
AB  - BACKGROUND: Growing attention has been paid to the effects of food flavor
      components on alleviating negative brain functions caused by stressful
      lifestyles. In this study, we investigated the alleviating effect of two kinds of
      black tea aromas on physical and psychological stress induced by the Uchida
      Kraepelin test, based on salivary chromogranin-A (CgA) levels as a stress marker
      and subjective evaluations (Profile of Mood States). RESULTS: Compared with the
      water exposure control, inhaling black tea aroma (Darjeeling and Assam in this
      study) induced lower salivary CgA concentration levels after 30 min of mental
      stress load tasks. This anti-stress effect of black tea aroma did not differ
      between the two tea types even though the concentration of the anti-stress
      components in the Darjeeling tea aroma was higher than that in the Assam aroma.
      However, Darjeeling tea aroma tended to decrease the tension and/or anxiety score
      immediately after the first exposure. CONCLUSIONS: Inhaling black tea aroma may
      diminish stress levels caused by arithmetic mental stress tasks, and Darjeeling
      tea aroma tended to improve mood before mental stress load.

PMID- 29361989
TI  - Atrial septal defect in a patient with congenital disorder of glycosylation type
      1a: a case report.
AB  - BACKGROUND: Atrial septal defect often become more severe when encountered in
      genetic syndromes. Congenital disorder of glycosylation type 1a is an inherited
      metabolic disorder associated with mutations in PMM2 gene and can affect almost
      all organs. Cardiac abnormalities vary greatly in congenital disorder of
      glycosylation type 1a and congenital heart defects have already been reported,
      but there is little knowledge about the effect of this inherited disorder on an
      existing congenital heart defect. Herein we report for the first time on a baby
      with congenital disorder of glycosylation type 1a with atrial septal defect and
      make a comparison of changes in atrial septal defect by follow-ups to the age of
      3. CASE PRESENTATION: Our patient was an 8-month-old Han Chinese boy. At the
      initial visit, he presented with recurrent lower respiratory infection, heart
      murmur, psychomotor retardation, inverted nipples, and cerebellar atrophy.
      Echocardiography revealed a 8 mm secundum atrial septal defect with left-to-right
      shunt (Qp/Qs ratio 1.6). Enzyme testing of phosphomannomutase 2 demonstrated
      decreased levels of phosphomannomutase 2 activities in fibroblasts. Whole exon
      sequencing showed he was heterozygous for a frameshift mutation (p.I153X) and a
      missense mutation (p.I132T) in PMM2 gene. The diagnosis of congenital disorder of
      glycosylation type 1a with atrial septal defect was issued. Now, he is 3-years
      old at the time of this writing, with the development of congenital disorder of
      glycosylation type 1a (cerebellar atrophy become more severe and the symptom of
      nystagmus emerged), the size of atrial septal defect increased to 10 mm and the
      Qp/Qs ratio increased to 1.9, which suggested exacerbation of the atrial septal
      defect. Congenital heart defect-associated gene sequencing is then performed and
      shows there are no pathogenic mutations, which suggested intrinsic cardiac
      factors are not the cause of exacerbation of the atrial septal defect in our
      patient and it is reasonable to assume congenital disorder of glycosylation type
      1a can worsen the situation of the existing atrial septal defect. CONCLUSIONS:
      This report highlights the view that congenital disorders of glycosylation type
      1a should be excluded when faced with congenital heart defect with cerebellar
      atrophy or neurodevelopmental delay, especially when the situation of congenital
      heart defect becomes more and more severe.

PMID- 29361991
TI  - Reflections on wisdom at the end of life: qualitative study of hospice patients
      aged 58-97 years.
AB  - OBJECTIVE: Wisdom is a complex trait, and previous research has identified
      several components of wisdom. This study explored the possible impact of a
      diagnosis of a terminal illness on the conceptualization and evolution of wisdom
      while facing the end of life. DESIGN AND PARTICIPANTS: Semi-structured
      qualitative interviews were conducted with 21 hospice patients aged 58-97 years
      who were in the last six months of their life. METHODS: Hospice patients were
      asked to describe the core characteristics of wisdom, as well as how their
      terminal illness might have impacted their understanding of this concept. The
      interviews were audiotaped, transcribed, and coded by the research team using a
      grounded theory analytic approach based on coding consensus, co-occurrence, and
      comparison. RESULTS: Broad concepts of wisdom described by the hospice patients
      align with the extant literature, thereby supporting those general
      conceptualizations. In addition, hospice patients described how their life
      perspectives shifted after being diagnosed with a terminal illness. Post-illness
      wisdom can be characterized as a dynamic balance of actively accepting the
      situation while simultaneously striving for galvanized growth. This delicate
      tension motivated the patients to live each day fully, yet consciously plan for
      their final legacy. CONCLUSION: The end of life offers a unique perspective on
      wisdom by highlighting the modulation between actively accepting the current
      situation while continuing the desire to grow and change at this critical time.
      This paradox, when embraced, may lead to even greater wisdom while facing one's
      own mortality.

PMID- 29361990
TI  - Dietary inflammatory index and memory function: population-based national sample
      of elderly Americans.
AB  - The objective of this study was to examine the association between dietary
      inflammatory potential and memory and cognitive functioning among a
      representative sample of the US older adult population. Cross-sectional data from
      the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey were
      utilised to identify an aggregate sample of adults 60-85 years of age (n 1723).
      Dietary inflammatory index (DII(r)) scores were calculated using 24-h dietary
      recall interviews. Three memory-related assessments were employed, including the
      Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning
      subset, the Animal Fluency test and the Digit Symbol Substitution Test (DSST).
      Inverse associations were observed between DII scores and the different memory
      parameters. Episodic memory (CERAD) (b adjusted=-0.39; 95 % CI -0.79, 0.00),
      semantic-based memory (Animal Fluency Test) (b adjusted=-1.18; 95 % CI -2.17, 
      0.20) and executive function and working-memory (DSST) (b adjusted=-2.80; 95 % CI
      -5.58, -0.02) performances were lowest among those with the highest mean DII
      score. Though inverse relationships were observed between DII scores and memory
      and cognitive functioning, future work is needed to further explore the
      neurobiological mechanisms underlying the complex relationship between
      inflammation-related dietary behaviour and memory and cognition.

PMID- 29361992
TI  - Brain disorders? Not really... Why network structures block reductionism in
      psychopathology research.
AB  - In the past decades, reductionism has dominated both research directions and
      funding policies in clinical psychology and psychiatry. However, the intense
      search for the biological basis of mental disorders has not resulted in
      conclusive reductionist explanations of psychopathology. Recently, network models
      have been proposed as an alternative framework for the analysis of mental
      disorders, in which mental disorders arise from the causal interplay between
      symptoms. In this paper, we show that this conceptualization can help understand
      why reductionist approaches in psychiatry and clinical psychology are on the
      wrong track. First, symptom networks preclude the identification of a common
      cause of symptomatology with a neurobiological condition, because in symptom
      networks there is no such common cause. Second, symptom network relations depend
      on the content of mental states and as such feature intentionality. Third, the
      strength of network relations is highly likely to partially depend on cultural
      and historical contexts as well as external mechanisms in the environment. Taken
      together, these properties suggest that, if mental disorders are indeed networks
      of causally related symptoms, reductionist accounts cannot achieve the level of
      success associated with reductionist disease models in modern medicine. As an
      alternative strategy, we propose to interpret network structures in terms of D.
      C. Dennett's (1987) notion of real patterns, and suggest that, instead of being
      reducible to a biological basis, mental disorders feature biological and
      psychological factors that are deeply intertwined in feedback loops. This
      suggests that neither psychological nor biological levels can claim causal or
      explanatory priority, and that a holistic research strategy is necessary for
      progress in the study of mental disorders.

PMID- 29361993
TI  - The Flint Food Store Survey: combining spatial analysis with a modified Nutrition
      Environment Measures Survey in Stores (NEMS-S) to measure the community and
      consumer nutrition environments.
AB  - OBJECTIVE: The goal of the present study was to use a methodology that accurately
      and reliably describes the availability, price and quality of healthy foods at
      both the store and community levels using the Nutrition Environment Measures
      Survey in Stores (NEMS-S), to propose a spatial methodology for integrating these
      store and community data into measures for defining objective food access.
      SETTING: Two hundred and sixty-five retail food stores in and within 2 miles (3.2
      km) of Flint, Michigan, USA, were mapped using ArcGIS mapping software. DESIGN: A
      survey based on the validated NEMS-S was conducted at each retail food store.
      Scores were assigned to each store based on a modified version of the NEMS-S
      scoring system and linked to the mapped locations of stores. Neighbourhood
      characteristics (race and socio-economic distress) were appended to each store.
      Finally, spatial and kernel density analyses were run on the mapped store scores
      to obtain healthy food density metrics. RESULTS: Regression analyses revealed
      that neighbourhoods with higher socio-economic distress had significantly lower
      dairy sub-scores compared with their lower-distress counterparts (beta
      coefficient=-1.3; P=0.04). Additionally, supermarkets were present only in
      neighbourhoods with <60 % African-American population and low socio-economic
      distress. Two areas in Flint had an overall NEMS-S score of 0. CONCLUSIONS: By
      identifying areas with poor access to healthy foods via a validated metric, this
      research can be used help local government and organizations target interventions
      to high-need areas. Furthermore, the methodology used for the survey and the
      mapping exercise can be replicated in other cities to provide comparable results.

PMID- 29361994
TI  - Why do patients with minor complaints choose emergency departments and does
      satisfaction with primary care services influence their decisions? - CORRIGENDUM.

PMID- 29361995
TI  - The effects of psychotherapy for depression on anxiety symptoms: a meta-analysis.
AB  - BACKGROUND: More than half of patients who present with depressive disorders also
      have elevated comorbid anxiety symptoms. Given the high comorbidity between these
      disorders, it is important to understand the extent that psychotherapies for
      depression additionally ameliorate symptoms of anxiety. METHODS: Systematic
      searches were conducted in PubMed, PSYCinfo, EMBASE, and the Cochrane Registry of
      Controlled Trials. Included studies were randomized controlled trials that
      compared psychotherapy compared with a control condition for the treatment of
      adults with a primary diagnosis or elevated symptoms of depression and that
      examined the effects of treatment on anxiety outcomes. Acute phase depression and
      anxiety (continuous measure) outcomes were extracted. Effect sizes were
      calculated by subtracting the average post-treatment scores of the psychotherapy
      group from the average post-treatment scores of the comparison group divided by
      the pooled standard deviation. RESULTS: Fifty-two studies of varying quality met
      the inclusion criteria. Pooled effect sizes showed that anxiety outcomes were
      significantly lower in the psychotherapy conditions than in control conditions at
      post-treatment [g = 0.52; 95% confidence interval (CI) 0.44-0.60; NNT (numbers
      needed-to-treat) = 3.50]. Moderate heterogeneity was observed (I2 = 55%, 95% CI
      40-66). Bivariate metaregression analysis revealed a significant association
      between depression and anxiety effect sizes at post-treatment Longer-term follow
      ups of up to 14 months post-baseline showed indications for a small lasting
      effect of psychotherapy on anxiety outcomes (g = 0.27). CONCLUSIONS: This meta
      analysis provides evidence that psychotherapy aimed at depression can also reduce
      anxiety symptoms in relation to control conditions.

PMID- 29361996
TI  - Ensuring caregivers are part of palliative care service delivery.

PMID- 29361997
TI  - An ecological momentary assessment evaluation of emotion regulation abnormalities
      in schizophrenia.
AB  - BACKGROUND: Prior studies using self-report questionnaires and laboratory-based
      methods suggest that schizophrenia is characterized by abnormalities in emotion
      regulation (i.e. using strategies to increase or decrease the frequency,
      duration, or intensity of negative emotion). However, it is unclear whether these
      abnormalities reflect poor emotion regulation effort or adequate effort, but
      limited effectiveness. It is also unclear whether dysfunction results primarily
      from one of the three stages of the emotion regulation process: identification,
      selection, or implementation. METHOD: The current study used ecological momentary
      assessment (EMA) to address these questions in the context of everyday
      activities. Participants included 28 outpatients diagnosed with schizophrenia
      (SZ) and 28 demographically matched healthy controls (CN) who completed 6 days of
      EMA reports of in-the-moment emotional experience, emotion regulation strategy
      use, and context. RESULTS: Results indicated that SZ demonstrated adequate
      emotion regulation effort, but poor effectiveness. Abnormalities were observed at
      each of the three stages of the emotion regulation process. At the identification
      stage, SZ initiated emotion regulation efforts at a lower threshold of negative
      emotion intensity. At the selection stage, SZ selected more strategies than CN
      and strategies attempted were less contextually appropriate. At the
      implementation stage, moderate to high levels of effort were ineffective at
      decreasing negative emotion. CONCLUSIONS: Findings suggest that although SZ
      attempt to control their emotions using various strategies, often applying more
      effort than CN, these efforts are unsuccessful; emotion regulation abnormalities
      may result from difficulties at the identification, selection, and implementation
      stages.

PMID- 29361998
TI  - Disease burden of psittacosis in the Netherlands.
AB  - Psittacosis (infection with Chlamydia psittaci) can have diverse presentations in
      humans, ranging from asymptomatic infection to severe systemic disease. Awareness
      of psittacosis and its presentations are low among clinicians and the general
      public. Therefore, underdiagnosis and thereby underestimation of the incidence
      and public health importance of psittacosis is very likely. We used the
      methodology developed for the Burden of communicable diseases in Europe toolkit
      of the European Centre for Disease Prevention and Control, to construct a model
      to estimate disease burden in disability-adjusted life years (DALYs) attributable
      to psittacosis. Using this model, we estimated the disease burden caused by
      psittacosis in the Netherlands to have been 222 DALY per year (95% CI 172-280)
      over the period 2012-2014. This is comparable with the amount of DALYs estimated
      to be due to rubella or shigellosis in the same period in the Netherlands. Our
      results highlight the public health importance of psittacosis and identify
      evidence gaps pertaining to the clinical presentations and prognosis of this
      disease.

PMID- 29361999
TI  - Bitter pills: the impact of medicare on mental health.
AB  - Medicare shifted the emphasis for mental health care into outpatient psychiatric
      wings connected to general hospitals and away from large custodial facilities
      that had been at the centre of the mental health system for decades. The shift to
      care in the community expanded the patient population, and arguably improved
      mental health care for many individuals who could now seek a variety of
      outpatient services rather than succumb to long-stay institutionalization.
      However, this shift also introduced new challenges as patients were increasingly
      expected to take responsibility for their own health care plans, whether that
      involved doctors' appointments, drug regimens, or the need to find sheltered
      employment, safe housing and a social support network. Analysing first-hand
      experiences suggests that despite the need for clinical care at times, the major
      challenges to independence are political and economic. In this paper, I examine
      some of these tradeoffs and consider some of the historical lessons for continued
      discussions on public policy in the mental health care arena.

PMID- 29362001
TI  - Quinlan, Texas.

PMID- 29362000
TI  - Determining Direction of Axonal Flow in the Equine Ramus Communicans by
      Ultrastructural Examination of the Plantar Nerves 2 Months after Transecting the
      Ramus.
AB  - The ramus communicans, neural connection between medial and lateral plantar
      nerves of the horse, was transected to determine the degree to which medial and
      lateral plantar nerves contribute to the plantar ramus. After 2 months, sections
      of plantar nerves immediately proximal and distal to the communicating branch
      were collected and processed for electron microscopy. All examined nerves had
      undergone Wallerian degeneration and contained regenerating and mature fibers.
      Layers of the myelin sheath were separated by spaces and vacuoles, indicating
      demyelination of medial and lateral plantar nerves. Shrunken axons varied in
      diameter and were surrounded by an irregular axolemma. Shrunken axoplasm of both
      myelinated and non-myelinated fibers contained ruptured mitochondria and cristae,
      disintegrating cytoskeleton, and vacuoles of various sizes. The cytoplasm of
      neurolemmocytes contained various-sized vesicles, ruptured mitochondria within a
      fragile basal lamina and myelin whorls of multilayered structures indicative of
      Wallerian degeneration. These ultrastructural changes, found proximal and distal
      to the ramus in medial and lateral plantar nerves, suggest that axonal flow is bi
      directional through the ramus communicans of the pelvic limbs of horses, a
      previously unreported finding. As well, maturity of nerves proximal and distal to
      the ramus indicates that all nerve fibers do not pass through the ramus.

PMID- 29362002
TI  - Relationship between welfare and individual ranging behaviour in commercial free
      range laying hens.
AB  - Laying hens housed in free-range systems have access to an outdoor range, and
      individual hens within a flock differ in their ranging behaviour. Whether there
      is a link between ranging and laying hen welfare remains unclear. We analysed the
      relationships between ranging by individual hens on a commercial free-range layer
      farm and behavioural, physiological and health measures of animal welfare. We
      hypothesised that hens that access the range more will be (1) less fearful in
      general and in response to novelty and humans, (2) have better health in terms of
      physical body condition and (3) have a reduced physiological stress response to
      behavioural tests of fear and health assessments than hens that use the range
      less. Using radio frequency identification tracking across two flocks, we
      recorded individual hens' frequency, duration and consistency of ranging. We also
      assessed how far hens ventured into the range based on three zones: 0 to 2.4, 2.4
      to 11.4 or >11.4 m from the shed. We assessed hen welfare using a variety of
      measures including: tonic immobility, open field, novel object, human approach,
      and human avoidance (HAV) behavioural tests; stress-induced plasma corticosterone
      response and faecal glucocorticoid metabolites; live weight, comb colour, and
      beak, plumage, footpad, and keel bone condition. Range use was positively
      correlated with plasma corticosterone response, faecal glucocorticoid
      metabolites, and greater flight distance during HAV. Hens that used the range
      more, moved towards rather than away from the novel object more often than hens
      that ranged less. Distance ranged from the shed was significantly associated with
      comb colour and beak condition, in that hens with darker combs and more intact
      beaks ranged further. Overall the findings suggest that there is no strong link
      between outdoor range usage and laying hen welfare. Alternatively, it may be that
      hens that differed in their ranging behaviour showed few differences in measures
      of welfare because free-range systems provide hens with adequate choice to cope
      with their environment. Further research into the relationship between individual
      range access and welfare is needed to test this possibility.

PMID- 29362003
TI  - Prevalence and factors associated with overweight and obesity among children from
      primary schools in urban areas of Lome, Togo.
AB  - OBJECTIVE: Overweight and obesity in childhood are serious public health issues,
      both in developing and developed countries. The present study aimed to ascertain
      overweight and obesity prevalence rates among Togolese schoolchildren in Lome,
      Togo, and their correlation with physical activity, socio-economic conditions and
      eating habits. DESIGN: Cross-sectional survey conducted in December 2015.
      Overweight and obesity were defined using age- and sex-specific BMI cut-off
      points of the International Obesity Task Force. Physical activity, socio-economic
      conditions and eating habits were assessed with a standardized questionnaire.
      Specially trained medical students interviewed children and collected the data.
      After bivariate regression analyses, factors associated with overweight/obesity
      were identified by multivariate logistic regression. Statistical significance was
      two-sided P<0.05. SETTING: Lome, Togo. SUBJECTS: Representative sample of 634
      children (288 boys, 346 girls), aged 8-17 years, who were studying in primary
      schools. RESULTS: Overweight and obesity respectively affected 5.2 and 1.9 % of
      children surveyed. Watching television (>4 h) on weekends (OR; 95 % CI: 3.8; 1.2,
      12.0, P=0.02) and medium dietary diversity score (3.0; 1.1, 8.1, P=0.03) were
      independently associated with overweight/obesity in a multivariate regression
      model. Eating breakfast in the school cafeteria (0.2; 0.1, 0.8, P=0.03) and
      eating fruits (0.4; 0.1, 0.9, P=0.03) significantly reduced the risk of
      overweight/obesity. CONCLUSIONS: Overweight and obesity prevalence were linked
      with sedentary behaviour and non-optimal food diversity. Promoting physical
      activity and fruit consumption should be explored as interventions to reduce and
      prevent overweight and obesity in Lome schoolchildren. In addition, preventive
      approaches in the social environment of children should be considered.

PMID- 29362004
TI  - Incidence and Risk Factors of Postoperative Pneumonia in Abdominal Operations
      Patients at a Teaching Hospital in China.

PMID- 29362005
TI  - A rare cause of cyanosis in newborns: arteriovenous fistula between the right
      pulmonary artery and the left atrium and its treatment.
AB  - The formation of a fistula between the right pulmonary artery and the left atrium
      via a sac is a very rare cyanotic congenital cardiopulmonary defect. A fistula
      between the pulmonary artery and left atrium may cause cardiac failure in utero.
      It can safely be treated surgically and in selected cases closure can be
      performed with transcatheter insertion of a device. In this article, we present a
      case with a fistula between the right pulmonary artery and the left atrium that
      was considered unsuitable for transcatheter closure and was safely treated
      surgically.

PMID- 29362006
TI  - Disaster Preparedness in Primary Care: Ready or Not?
AB  - : PurposeTo assess perceptions and attitudes toward disasters and disaster
      planning among outpatient primary care leaders. METHODS: Written surveys and semi
      structured interviews of non-physician clinical managers and physician medical
      directors were conducted using the 2009 H1N1 pandemic as a case-based scenario at
      5 university-affiliated family medicine clinics. Domains assessed included
      perceived pandemic threat; value, existence, and barriers to creating personal
      disaster plans; staff absenteeism estimates; barriers to work attendance.
      Quantitative and qualitative data were analyzed using descriptive statistics and
      content analysis with identification and coding of common themes, respectively.
      RESULTS: All 12 invited leaders participated and believed a personal disaster
      plan was important but only 2 had plans. None had ever discussed with their staff
      the importance of having a personal disaster plan. Two common barriers in
      creating a plan were low threat perception level and never considering the
      possibility of pandemic influenza. Only half of respondents could list common
      barriers preventing staff from working. Staff were confident employees would come
      to work during a disaster. CONCLUSION: Outpatient primary care leaders may hold
      misconceptions regarding future disasters, underestimate their potential impact
      on clinics, and lack personal preparedness. Further investigation and
      interventions are needed to ensure clinics can be prepared so they can function
      and help hospital and emergency services when disasters strike. (Disaster Med
      Public Health Preparedness. 2018;12:644-648).

PMID- 29362007
TI  - Building capacity in primary care: the implementation of a novel 'Pharmacy First'
      scheme for the management of UTI, impetigo and COPD exacerbation.
AB  - : Aim This service aimed to improve patient access to treatment for urinary tract
      infections (UTI), impetigo and exacerbation of chronic obstructive pulmonary
      disease (COPD) and relieve pressure on general practice and out of hours
      services. BACKGROUND: In 2016, a service (Pharmacy First) was introduced in Forth
      Valley for the management of UTI, impetigo and exacerbation of COPD using patient
      group directions in community pharmacies. Trained pharmacists supplied a limited
      range of prescription medicines. Pathways for GP referral were defined. After 5
      months of implementation, the service was evaluated. METHODS: A quantitative
      evaluation was undertaken. Feedback was sought from patients, GPs, pharmacists
      and GP reception staff, using structured questionnaires. Pharmacy records were
      used to assess referrals and pharmacy data summarised the number and type of
      consultations. Basic cost data was obtained from the Health Board. Findings In
      all, 75 pharmacies (of 76), and all 55 GP practices in the area, participated in
      the service. Over a 5-month period, 1189 cases were managed, the majority being
      for UTI (75.4%) followed by impetigo (15.2%), then COPD (9.3%). Of all cases,
      77.9% were prescribed medication by the pharmacist, 9.1% were given advice only
      and 16.7% were referred to the GP. Independent clinical assessment of a random
      sample of 30 GP referrals considered all to be 'appropriate'. Feedback was
      received from 69 pharmacists, 34 GPs, 54 reception staff and 73 patients.
      Patients were very satisfied with the service, most frequently citing the 'quick
      and efficient' access to treatment, and a 'professional service'. Two thirds of
      GPs (67%) and 59% of reception staff found the service useful, mainly because it
      reduced pressure on GP appointments. A further cost benefit evaluation would
      allow objective assessment of the value of this service.

PMID- 29362008
TI  - The impact of slow economic growth on health sector reform: a cross-national
      perspective.
AB  - This paper assesses recent health sector reform strategies across Europe adopted
      since the onset of the 2008 financial crisis. It begins with a brief overview of
      the continued economic pressure on public funding for health care services,
      particularly in tax-funded Northern European health care systems. While economic
      growth rates across Europe have risen a bit in the last year, they remain below
      the level necessary to provide the needed expansion of public health sector
      revenues. This continued public revenue shortage has become the central challenge
      that policymakers in these health systems confront, and increasingly constrains
      their potential range of policy options. The paper then examines the types of
      targeted reforms that various European governments have introduced in response to
      this increased fiscal stringency. Particularly in tax-funded health systems,
      these efforts have been focused on two types of changes on the production side of
      their health systems: consolidating and/or centralizing administrative authority
      over public hospitals, and revamping secondary and primary health services as
      well as social services to reduce the volume, cost and less-than-optimal outcomes
      of existing public elderly care programs. While revamping elderly care services
      also was pursued in the social health insurance (SHI) system in the Netherlands,
      both the Dutch and the German health systems also made important changes on the
      financing side of their health systems. Both types of targeted reforms are
      illustrated through short country case studies. Each of these country assessments
      flags up new mechanisms that have been introduced and which potentially could be
      reshaped and applied in other national health sector contexts. Reflecting the tax
      funded structure of the Canadian health system, the preponderance of cases
      discussed focus on tax-funded countries (Norway, Denmark, Sweden, Finland,
      England, Ireland), with additional brief assessments of recent changes in the SHI
      funded health systems in the Netherlands and Germany. The paper concludes that
      post-2008 European reforms have helped stretch existing public funds more
      effectively, but seem unlikely to resolve the core problem of inadequate overall
      public funding, particularly in tax-based health systems. This observation
      suggests that ongoing Canadian efforts to consolidate and better integrate its
      health care providers, while important, may not eliminate long-term health sector
      funding dilemmas.

PMID- 29362009
TI  - Feed efficiency and the liver proteome of fattening lambs are modified by feed
      restriction during the suckling period.
AB  - The present study was designed to describe the effects of early feed restriction
      of Merino lambs on feed efficiency during the fattening period by examining
      ruminal microbiota and fermentation parameters, gastrointestinal morphology,
      digestibility or liver proteome. In total, 24 male Merino lambs were randomly
      assigned to two experimental treatments (n=12 per treatment). Lambs of the first
      group (ad libitum (ADL)) were kept permanently with the dams, whereas the other
      12 lambs (restricted (RES)) were milk restricted. When lambs reached a live BW
      (LBW) of 15 kg, all the animals were offered the same complete pelleted diet (35
      g dry matter/kg LBW per day) until slaughter at a LBW of 27 kg. The RES lambs
      showed poorer feed efficiency during the fattening period when compared with the
      ADL group (feed to gain ratio, 3.69 v. 3.05, P<0.001). No differences were
      observed in ruminal microbiota, fermentation parameters or apparent
      digestibility. However, the proportion of the small intestine and the length of
      ileal villi were reduced in the RES lambs. In total, 26 spots/proteins were
      identified in the liver proteomic profile, with significant differences (P<0.05)
      between experimental treatments, suggesting a higher catabolism of proteins and a
      reduction in beta-oxidation of fatty acids in RES lambs when compared with the
      ADL animals. In conclusion, early feed restriction of Merino lambs during the
      suckling period promotes long-term effects on the small intestine and the
      proteomic profile of the liver, which may influence the metabolic use of
      nutrients, thus negatively affecting feed efficiency during the fattening phase.

PMID- 29362010
TI  - Stakeholder perceptions of a school food policy ten years on.
AB  - OBJECTIVE: To assess (i) the extent to which stakeholders have accepted and
      implemented a Healthy Food and Drink Policy for schools a decade after its
      introduction and (ii) any resulting implications for canteen profitability.
      DESIGN: Online survey distributed via electronic newsletter to school principals.
      SETTING: Western Australian public schools. SUBJECTS: Principals, teachers,
      canteen managers, and parents and citizens committee presidents (n 307). RESULTS:
      Large majorities of respondents reported that the policy has made the foods and
      drinks provided in schools healthier (85 %) and that the policy constitutes a
      good opportunity to teach children about healthy eating (90 %). Only small
      proportions of respondents felt it had been difficult to implement the policy in
      their schools (13 %) or that the policy fails to accommodate parents' rights to
      choose the foods consumed by their children (16 %). Most of the policy outcomes
      assessed in both the initial post-implementation evaluation (2008) and the 10
      year follow-up evaluation (2016) demonstrated significant improvement over time.
      CONCLUSIONS: The study results indicate that comprehensive school food policies
      can favourably influence the foods and drinks provided on school premises and can
      be highly acceptable to key stakeholders, without adversely affecting
      profitability. The results are encouraging for policy makers in other
      jurisdictions considering the implementation of similar policies.

PMID- 29362011
TI  - Neuropsychiatric symptoms and cognitive profile in mild cognitive impairment with
      Lewy bodies.
AB  - BACKGROUND: The accurate clinical characterisation of mild cognitive impairment
      (MCI) is becoming increasingly important. The aim of this study was to compare
      the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI
      LB) with Alzheimer's disease MCI (MCI-AD). METHODS: Participants were ?60 years
      old with MCI. Each had a thorough clinical and neuropsychological assessment and
      2beta-carbomethoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single
      photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or
      more diagnostic features of dementia with Lewy bodies were present (visual
      hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement
      sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric
      Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence
      of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic
      criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
      RESULTS: MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 +/- 1.1 v.
      0.7 +/- 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms,
      compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects
      scored lower on tests of attention, visuospatial function and verbal fluency.
      However, cognitive test scores alone did not accurately differentiate MCI-LB from
      MCI-AD. CONCLUSIONS: MCI-LB is associated with neuropsychiatric symptoms and a
      cognitive profile similar to established DLB. This supports the concept of
      identifying MCI-LB based on the presence of core diagnostic features of DLB and
      abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric
      clinical features identified in the 2017 DLB diagnostic criteria was helpful in
      differentiating between MCI-LB and MCI-AD.

PMID- 29362012
TI  - Use and non-use values as motivational construct dimensions for farm animal
      welfare: impacts on the economic outcome for the farm.
AB  - This study explored how farmers' motivation in terms of use values and/or non-use
      values to work with farm animal welfare are associated with the economic outcome
      for the farm. Use values in farm animal welfare refer to economic value derived
      from productivity and profitability considerations. Non-use values in farm animal
      welfare refer to economic value derived from good animal welfare, irrespective of
      the use the farmer derives from the animal, currently or in the future. The
      analysis was based on detailed information about the income statements of a
      sample of Swedish dairy farmers, obtained from the Swedish Farm Economic Survey,
      complemented with survey information about their perceived use and non-use values
      in farm animal welfare. The findings suggest that farm economic outcome is
      significantly associated with motivation in terms of use values, but not so much
      with motivation in terms of non-use values. This is interesting from a policy
      point of view, because it indicates that farmers with different approaches to
      farm animal welfare may experience different economic outcomes for their farms.
      Findings can, for instance, be used to strengthen farmers' engagement in various
      private quality assurance standards, which generally focus on values of non-use
      type, by pointing to that realisation of such values will not impair the economic
      outcome of the farms. Moreover, findings also suggest that farmers' economic
      incentives for engagement in such standards may need to be further strengthened
      in order to become more attractive, as findings point to that a focus on non-use
      values generally is not associated with more favourable economic outcomes.

PMID- 29362013
TI  - Dietary patterns are associated with child, maternal and household-level
      characteristics and overweight/obesity among young Samoan children.
AB  - OBJECTIVE: Among young Samoan children, diet may not be optimal: in 2015, 16.1 %
      of 24-59-month-olds were overweight/obese, 20.3 % stunted and 34.1 % anaemic. The
      present study aimed to identify dietary patterns among 24-59-month-old Samoan
      children and evaluate their association with: (i) child, maternal and household
      characteristics; and (ii) nutritional status indicators (stunting,
      overweight/obesity, anaemia). DESIGN: A community-based, cross-sectional study.
      Principal component analysis on 117 FFQ items was used to identify empirical
      dietary patterns. Distributions of child, maternal and household characteristics
      were examined by factor score quintiles. The regression of nutritional status
      indicators v. these quintiles was performed using logistic regression models.
      SETTING: Ten villages on the Samoan island of Upolu. SUBJECTS: A convenience
      sample of mother-child pairs (n 305). RESULTS: Two dietary patterns, modern and
      neo-traditional, emerged. The modern pattern was loaded with 'westernized' foods
      (red meat, condiments and snacks). The neo-traditional pattern included
      vegetables, local starches, coconuts, fish and poultry. Following the modern diet
      was associated with urban residence, greater maternal educational attainment,
      higher socio-economic status, lower vitamin C intake and higher sugar intake.
      Following the neo-traditional diet was associated with rural residence, lower
      socio-economic status, higher vitamin C intake and lower sugar intake. While
      dietary patterns were not related to stunting or anaemia, following the neo
      traditional pattern was positively associated with child overweight/obesity
      (adjusted OR=4.23, 95 % CI 1.26, 14.17, for the highest quintile, P-trend=0.06).
      CONCLUSIONS: Further longitudinal monitoring and evaluation of early childhood
      growth and development are needed to understand the influences of early diet on
      child health in Samoa.

PMID- 29362014
TI  - Use of the Community Assessment for Public Health Response (CASPER) Method by
      Public Health Agencies in Texas, 2001-2015.
AB  - OBJECTIVES: The use of the Community Assessment for Public Health Emergency
      Response (CASPER) method in disaster and non-disaster settings continues to grow.
      While CASPERs flexibility has been well demonstrated, the documentation of
      specific actions that have resulted from the utilization of CASPER data has been
      limited. We attempted to document changes in emergency preparedness planning and
      policy based on CASPER data. METHODS: Written reports from 19 CASPERs conducted
      in Texas between 2001 and 2015 were collected. Key informant interviews were
      conducted with 9 public health staff knowledgeable about the CASPERs. Written
      reports and interview transcripts were coded and analyzed for themes. RESULTS:
      Few specific outcomes could be documented beyond a single successful grant
      application. Respondents felt CASPER data was not duplicative and was useful for
      improving existing plans. CASPER is seen as an effective way to enhance
      relationships with communities and partnerships with agencies including Emergency
      Management. CONCLUSION: As the use of CASPER grows, it is increasingly important
      to document any specific and measurable benefits, actions, and changes to
      planning or policy taken as the result of data collected using the CASPER method.
      Without measurable outputs and outcomes, support for the use of CASPER from
      decision-makers may begin to wane. (Disaster Med Public Health Preparedness.
      2018;page 1 of 5).

PMID- 29362015
TI  - Differential virulence of camel Trypanosoma evansi isolates in mice.
AB  - This study assessed the virulence of Trypanosoma evansi, the causative agent of
      camel trypanosomiasis (surra), affecting mainly camels among other hosts in
      Africa, Asia and South America, with high mortality and morbidity. Using Swiss
      white mice, we assessed virulence of 17 T. evansi isolates collected from surra
      endemic countries. We determined parasitaemia, live body weight, packed cell
      volume (PCV) and survivorship in mice, for a period of 60 days' post infection.
      Based on survivorship, the 17 isolates were classified into three virulence
      categories; low (31-60 days), moderate (11-30 days) and high (0-10 days).
      Differences in survivorship, PCV and bodyweights between categories were
      significant and correlated (P < 0.05). Of the 10 Kenyan isolates, four were of
      low, five moderate and one (Type B) of high virulence. These findings suggest
      differential virulence between T. evansi isolates. In conclusion, these results
      show that the virulence of T. evansi may be region specific, the phenotype of the
      circulating parasite should be considered in the management of surra. There is
      also need to collect more isolates from other surra endemic regions to confirm
      this observation.

PMID- 29362016
TI  - Effects of fermented soybean meal on carbon and nitrogen metabolisms in large
      intestine of piglets.
AB  - Fermented soybean meal (FSM), which has lower anti-nutritional factors and higher
      active enzyme, probiotic and oligosaccharide contents than its unfermented form,
      has been reported to improve the feeding value of soybean meal, and hence, the
      growth performance of piglets. However, whether FSM can affect the bacterial and
      metabolites in the large intestine of piglets remains unknown. This study
      supplemented wet-FSM (WFSM) or dry-FSM (DFSM) (5% dry matter basis) in the diet
      of piglets and investigated its effects on carbon and nitrogen metabolism in the
      piglets' large intestines. A total of 75 41-day-old Duroc*Landrace*Yorkshire
      piglets with an initial BW of 13.14+/-0.22 kg were used in a 4-week feeding
      trial. Our results showed that the average daily gain of piglets in the WFSM and
      DFSM groups increased by 27.08% and 14.58% and that the feed conversion ratio
      improved by 18.18% and 7.27%, respectively, compared with the control group. Data
      from the prediction gene function of Phylogenetic Investigation of Communities by
      Reconstruction of Unobserved States (PICRUSt) based on 16S ribosomal RNA (rRNA)
      sequencing showed that carbohydrate metabolism function families in the WFSM and
      DFSM groups increased by 3.46% and 2.68% and that the amino acid metabolism
      function families decreased by 1.74% and 0.82%, respectively, compared with the
      control group. These results were consistent with those of other metabolism
      studies, which showed that dietary supplementation with WFSM and DFSM increased
      the level of carbohydrate-related metabolites (e.g. 4-aminobutanoate, 5
      aminopentanoate, lactic acid, mannitol, threitol and beta-alanine) and decreased
      the levels of those related to protein catabolism (e.g. 1,3-diaminopropane,
      creatine, glycine and inosine). In conclusion, supplementation with the two forms
      of FSM improved growth performance, increased metabolites of carbohydrate and
      reduced metabolites of protein in the large intestine of piglets, and WFSM
      exhibited a stronger effect than DFSM.

PMID- 29362017
TI  - Expanding the breadth of Medicare: learning from Australia.
AB  - The design of Australia's Medicare programme was based on the Canadian scheme,
      adapted somewhat to take account of differences in the constitutional division of
      powers in the two countries and differences in history. The key elements are very
      similar: access to hospital services without charge being the core similarity,
      universal coverage for necessary medical services, albeit with a variable co
      payment in Australia, the other. But there are significant differences between
      the two countries in health programmes - whether or not they are labelled as
      'Medicare'. This paper discusses four areas where Canada could potentially learn
      from Australia in a positive way. First, Australia has had a national
      Pharmaceutical Benefits Scheme for almost 70 years. Second, there have been
      hesitant extensions to Australia's Medicare to address the increasing prevalence
      of people with chronic conditions - extensions which include some payments for
      allied health professionals, 'care coordination' payments, and exploration of
      'health care homes'. Third, Australia has a much more extensive system of support
      for older people to live in their homes or to move into supported residential
      care. Fourth, Australia has gone further in driving efficiency in the hospital
      sector than has Canada. Finally, the paper examines aspects of the Australian
      health care system that Canada should avoid, including the very high level of out
      of-pocket costs, and the role of private acute inpatient provision.

PMID- 29362018
TI  - Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation,
      adipocyte size and pyroptosis during obesity.
AB  - It has been established that ingestion of a high-fat diet increases the blood
      levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut.
      Obesity is characterised by low-grade systemic and adipose tissue inflammation.
      This is suggested to be implicated in the metabolic syndrome and obesity. In the
      present review, we hypothesise that LPS directly and indirectly participates in
      the inflammatory reaction in adipose tissue during obesity. The experimental
      evidence shows that LPS is involved in the transition of macrophages from the M2
      to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase
      4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e.
      pyroptosis), which also occurs after infection with intracellular pathogens.
      Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are
      more metabolically active and potentially more exposed to LPS than small
      adipocytes are. Thus, LPS might be involved in defining the adipocyte death size
      and the formation of crown-like structures. The adipocyte death size is reached
      when the intracellular concentration of LPS initiates pyroptosis. The mechanistic
      details remain to be elucidated, but the observations indicate that adipocytes
      are stimulated to cell death by processes that involve LPS from the gut
      microbiota. There is a complex interplay between the composition of the diet and
      microbiota. This influences the amount of LPS that is translocated from the gut.
      In particular, the lipid content of a meal may correlate with the amount of LPS
      built in to chylomicrons.

PMID- 29362019
TI  - The influence of azaperone treatment at weaning on reproductive function in sows:
      ovarian activity and endocrine profiles during the weaning-to-ovulation interval.
AB  - Azaperone can reduce stress caused by weaning and relocation of breeding sows,
      but its effects on reproductive processes are still poorly understood. The
      primary aim of this study was to describe and compare the endocrine and ovarian
      activity in ultrasonographically monitored second parity sows, with or without
      azaperone treatment at weaning (2 mg/kg BW i.m.). The intervals from weaning to
      the onset of estrus and ovulation were both greater (P<0.05) in azaperone-treated
      (n=12) than in control sows (n=12) by ~12 h. Mean daily growth rates of
      identified antral follicles were less (P<0.05) in azaperone-treated than in
      control sows (1.08+/-0.17 v.1.23+/-0.18 mm/day; mean+/-SD) and treated animals
      exceeded (P<0.05) controls in the mean ovulation rate (13.7+/-1.3 v. 12.6+/-1.2).
      A transient suppression of cortisol release was observed in the treatment group
      (at 10 and 30 min after azaperone injections) but circulating cortisol
      concentrations were variable in both groups of sows for the remainder of the
      study. The preovulatory rise in LH and estradiol secretion was delayed (P<0.05),
      and the duration of the LH surge was greater (P<0.001) in azaperone-treated sows
      compared with their control counterparts. The amplitude of episodic fluctuations
      in serum cortisol concentrations was correlated with the number of stillborn
      piglets in control sows (r=0.63, P=0.04). The amplitude and concentration of the
      preovulatory rise in estradiol secretion were negatively correlated with
      ovulatory response and litter size (r=-0.63 to -0.82, P<0.05), whereas the time
      at which the LH surge ended was directly related to the number of live-born
      piglets (r=0.82, P=0.002) in azaperone-treated animals. The present results
      indicate that administration of azaperone at weaning had a profound effect on
      preovulatory LH secretion as well as growth kinetics and estrogenicity of ovarian
      antral follicles. However, the causative associations among various
      characteristics of the preovulatory LH discharge, ovarian and adrenal steroid
      secretion post-weaning, and reproductive variables in sows remain equivocal.

PMID- 29362020
TI  - Verbal Memory Deficits in OEF/OIF/OND Veterans Exposed to Blasts at Close Range.
AB  - OBJECTIVES: This study investigated the relationship between close proximity to
      detonated blast munitions and cognitive functioning in OEF/OIF/OND Veterans.
      METHODS: A total of 333 participants completed a comprehensive evaluation that
      included assessment of neuropsychological functions, psychiatric diagnoses and
      history of military and non-military brain injury. Participants were assigned to
      a Close-Range Blast Exposure (CBE) or Non-Close-Range Blast Exposure (nonCBE)
      group based on whether they had reported being exposed to at least one blast
      within 10 meters. RESULTS: Groups were compared on principal component scores
      representing the domains of memory, verbal fluency, and complex attention
      (empirically derived from a battery of standardized cognitive tests), after
      adjusting for age, education, PTSD diagnosis, sleep quality, substance abuse
      disorder, and pain. The CBE group showed poorer performance on the memory
      component. Rates of clinical impairment were significantly higher in the CBE
      group on select CVLT-II indices. Exploratory analyses examined the effects of
      concussion and multiple blasts on test performance and revealed that number of
      lifetime concussions did not contribute to memory performance. However,
      accumulating blast exposures at distances greater than 10 meters did contribute
      to poorer performance. CONCLUSIONS: Close proximity to detonated blast munitions
      may impact memory, and Veterans exposed to close-range blast are more likely to
      demonstrate clinically meaningful deficits. These findings were observed after
      statistically adjusting for comorbid factors. Results suggest that proximity to
      blast should be considered when assessing for memory deficits in returning
      Veterans. Comorbid psychiatric factors may not entirely account for cognitive
      difficulties. (JINS, 2018, 24, 466-475).

PMID- 29362021
TI  - Let-7c Inhibits the Proliferation, Invasion, and Migration of Glioma Cells via
      Targeting E2F5.
AB  - As a member of the miRNA family, let-7c has been identified as a tumor suppressor
      in many cancers. However, the molecular biological function of let-7c in glioma
      has not been elucidated. The aim of this study was to explore let-7c expression
      levels and evaluate its function in glioma cells. We first measured the
      expression of let-7c in four glioma cell lines and a normal cell line by
      quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR),
      and the results showed that let-7c was downregulated in glioma cells. By applying
      gain-of-function and loss-of-function assays, the experiments suggested that
      dysregulation of let-7c could obviously affect cell proliferation, metastasis,
      and invasion. Based on online bioinformatics analysis and Dual-Luciferase
      Reporter assays, we found that E2F5 was a target gene of let-7c and contributed
      to the function of let-7c in glioma cells. Our investigations indicated that loss
      of let-7c contributed to the progression of glioma cells.

PMID- 29362023
TI  - Expression of TAp73alpha affects the therapy effect of chemotherapy drugs in
      gastric cancer.
AB  - The transcription factor TAp73, a transcriptionally active isoform of p73, has
      high structure and function similaritieswith its homolog p53, therefore, are
      thought to be a cancer therapy candidate target. However, there is still a
      controversy about the tumor suppressor role of TAp73, since it has been found in
      numerous studies that TAp73 expression is elevated in different cancers. Thus, we
      take effort to clarify the influence of TAp73 on gastric cancer (GC)
      chemotherapy. Multiple cell lines of GC such as SNU-1, SNU-3, and AGS were
      applied to investigate expression of TAp73. Flow cytometry was utilized to detect
      apoptosis, revealing how TAp73 overexpression affected anticancer drug (ACD).
      Additionally, we explored how TAp73 overexpression influenced apoptotic cells of
      neoplastic tissues and tumor size of nude mice in vivo. Our results indicated
      that TAp73 was down-regulated in GC cells after chemotherapy drugs treatment.
      Besides, enforced expression of TAp73 affects chemotherapeutic drugs induced GC
      cell apoptosis, which is dependent on p53. The expression of TAp73 was regulated
      by its transcription factor, E2F1, in response to chemotherapy drugs. Our in vivo
      xenograft results also suggested that transfection of TAp73 affects the tumor
      suppression effect of 5-FU. Consequently, the findings of our study demonstrate
      that E2F1 and TAp73alpha are oncogenic and throw light upon the underlying
      mechanism of their role against apoptosis.

PMID- 29362024
TI  - Models of nutrition-focused continuing education programs for nurses: a
      systematic review of the evidence.
AB  - Nurses are well-positioned to provide basic nutrition education and reinforce
      nutrition messages to patients in hospital and primary care settings. Despite
      this, nurses may not receive adequate training to provide this service, and there
      is limited opportunity for nurses to engage in nutrition-focused continuing
      education (CE). The aim of this review was to determine whether nurse nutrition
      education results in improved knowledge and practices; and explore which models
      of CE for nutrition may be most acceptable and effective in practice. Web of
      Science and Scopus were searched for case-series studies published between 2000
      and 2016 that investigated changes in nutrition knowledge of nurses and midwives.
      Only studies that could transcend to nurses providing patient nutrition education
      were included. Twelve articles met the eligibility criteria. Articles are
      explored in terms of mode of delivery, duration of intervention and educational
      strategies employed. Nutrition CE programs that are delivered face-to-face or by
      self-directed learning manuals, which utilise active learning strategies, are
      positively associated with improvements in nutrition knowledge. Web-based CE and
      self-directed learning may be favourable modes of delivery as they may assist in
      addressing resource and time contraints.

PMID- 29362025
TI  - Rigorous follow-up systems for abnormal results are essential to improve health
      outcomes for Aboriginal and Torres Strait Islander people.

PMID- 29362026
TI  - Anatomy and Physiology of the Lesser Metatarsophalangeal Joints.
AB  - Knowledge and command of anatomy is paramount to effectively treating disorders
      of the lesser metatarsophalangeal (MTP) joints. The osseous structures consist of
      the proximal phalanx of the toe and the metatarsal head. The soft tissues on the
      dorsum of the MTP joint include the joint capsule and the tendons of extensor
      digitorum longus and extensor digitorum brevis. The proper and accessory
      collateral ligaments form the medial and lateral walls and contribute to
      stability in the coronal and sagittal planes. The plantar plate forms the plantar
      border of the MTP joint and stabilizes the MTP joint against hyperextension and
      dorsal translation.

PMID- 29362027
TI  - Lesser Metatarsophalangeal Joint Instability: Treatment with Tendon Transfers.
AB  - Complex digital deformities and metatarsophalangeal joint instability encompass a
      wide range of pathology, and we must identify the different degrees of
      ligamentous disruption. It is important to address a combination of procedures to
      treat gross deformities of the lesser toes. Surgical treatment should be
      individualized and requires a sequential process for adequate reduction and
      deformity correction. There is no gold standard procedure for every deformity.
      Although residual stiffness can result from tendon transfer, overall patient
      satisfaction levels remain high when it is performed under the proper indications
      and concomitantly with other procedures to gain full correction of these
      challenging deformities.

PMID- 29362028
TI  - Lesser Metatarsophalangeal Joint Instability: Advancements in Plantar Plate
      Reconstruction.
AB  - The plantar plate and associated collateral ligaments are the main stabilizers of
      each of the lesser metatarsophalangeal joints. Although clinical examination and
      plain radiographs are usually sufficient to establish the diagnosis of a plantar
      plate tear, MRI or fluoroscopic arthrograms may help in specific cases. Recent
      results with a dorsal approach to plantar plate repair are promising with respect
      to pain relief and patient satisfaction.

PMID- 29362029
TI  - Managing Complications of Lesser Toe and Metatarsophalangeal Joint Surgery.
AB  - The anatomy of the lesser toes is highly complicated and not yet well understood.
      The high propensity of the metatarsophalangeal joint to develop hyperextension
      deformity should be recognized. Surgeons should provide each patient with a
      realistic expectation for lesser toe reconstructive procedures. A successful
      surgical result requires a well-planned procedure, accurate execution using
      proper techniques, and meticulous postoperative care. When complications occur,
      surgeons should identify culprits so that proper treatment strategies can be
      successfully executed. This article discusses a wide array of tactics to manage
      common complications in lesser toe surgery.

PMID- 29362030
TI  - Treatment of Freiberg Disease.
AB  - Freiberg disease, or osteochondrosis of the lesser metatarsal head, usually
      involves the second metatarsal and presents during the second or third decades of
      life. Conservative measures to relieve pressure on the affected metatarsal head
      are the first-line treatments, with good success for Smillie stage I to III
      disease. Operative treatments are divided into joint-preserving and joint
      reconstructing procedures. Although multiple case series describe success with
      numerous techniques, there are no established guidelines for treatment. All
      surgical techniques carry a risk of a stiff or floating toe and transfer
      metatarsalgia. This article reviews the current surgical treatment options for
      Freiberg disease.

PMID- 29362031
TI  - Treatment of Metatarsalgia with Distal Osteotomies.
AB  - Many different distal metatarsal osteotomies have been described in the surgical
      treatment of metatarsalgia. The surgeon should use such osteotomies judiciously,
      and indeed, in the author's experience, they are infrequently required and are
      certainly not a first port of call. In cases where nonoperative treatments have
      failed, a thorough understanding of the causes of metatarsalgia and a detailed
      clinical assessment of the patient are essential if good surgical outcomes are to
      be achieved. If using distal metatarsal osteotomies as part of the surgical plan,
      then the author favors extra-articular percutaneous osteotomies to minimize
      postoperative stiffness.

PMID- 29362032
TI  - Treatment of Metatarsalgia with Proximal Osteotomies.
AB  - Metatarsalgia is among the most common sources of forefoot pain. Proximal
      metatarsal osteotomies are an important technique in the armamentarium of the
      surgeon treating metatarsalgia that has failed nonoperative management. Proximal
      osteotomies can provide powerful deformity correction with precise control to
      both shorten and elevate the metatarsal head. However, they can be technically
      challenging, difficult to attain satisfactory fixation, require increased
      postoperative immobilization, and can result in transfer lesions. There are
      numerous described techniques with little supporting evidence and more research
      is needed to establish the optimal procedure to reliably alleviate patient's
      symptoms while minimizing complications.

PMID- 29362033
TI  - Metatarsal Osteotomies: Complications.
AB  - Metatarsal osteotomies can be divided into proximal and distal. The proximal
      osteotomies, such as the oblique, segmental, set cut, and Barouk-Rippstein
      Toullec (BRT) osteotomy, all provide the ability to significantly change the
      position of the metatarsal head without violating the joint. These osteotomies,
      however, have a high rate of nonunion when done without internal fixation and can
      lead to transfer metatarsalgia when done without regard to the parabola of
      metatarsal head position. Distal osteotomies such as the Weil and Helal offer
      superior healing but have an increased incidence of recurrent metatarsalgia,
      joint stiffness, and floating toe.

PMID- 29362034
TI  - Gastrocnemius Recession for Metatarsalgia.
AB  - Metatarsalgia is a common cause of plantar forefoot pain. Causes of metatarsalgia
      include foot anatomy, gait mechanics, and foot and ankle deformity. One specific
      cause, mechanical metatarsalgia, occurs because of gastrocnemius muscle
      contracture, which overloads the forefoot. Muscular imbalance of the
      gastrocnemius complex alters gait mechanics, which increases recruitment of the
      toe extensor musculature, thereby altering forefoot pressure. Patients with
      concomitant metatarsalgia and gastrocnemius contracture demonstrate ankle equinus
      and a positive Silfverskiold test. Nonoperative therapeutic modalities are
      mainstays of treatment. In patients in whom these treatments fail to provide
      metatarsalgia symptomatic relief, gastrocnemius muscle lengthening is a
      therapeutic option.

PMID- 29362035
TI  - Treatment of Flexible Lesser Toe Deformities.
AB  - Lesser toe deformities are among the most common complaints presented to foot and
      ankle specialists. These deformities present in variable ways, which makes
      surgical decision making complex. For every type of deformity, there could be a
      combination of soft tissues and bony procedures, chosen according to the
      surgeon's preferences. This article first describes modern classification of
      lesser toe deformities, and then presents the different treatments and procedures
      available for those flexible deformities. In addition, this article proposes an
      algorithm based on clinical/radiological evaluation and step-by-step surgical
      decision making.

PMID- 29362036
TI  - Conservative Management of Metatarsalgia and Lesser Toe Deformities.
AB  - There are several forefoot conditions that can result in metatarsal head pain.
      Various points of the gait cycle can predispose the metatarsal heads to pain
      based on intrinsic and extrinsic imbalances. Metatarsalgia can further be
      classified according to primary, secondary, or iatrogenic etiologies. Within
      these groups, conservative management is the first line of treatment and can
      often obviate surgical intervention. Depending on the cause of pain, proper
      shoewear, orthoses, and inserts coupled with targeted physical therapy can
      alleviate most symptoms of metatarsalgia and lesser toe deformities.

PMID- 29362037
TI  - Treatment of Rigid Hammer-Toe Deformity: Permanent Versus Removable Implant
      Selection.
AB  - Hammer-toe deformities that fail nonoperative treatment can be successfully
      addressed with proximal interphalangeal joint resection arthroplasty or fusion.
      The goal of surgery is to eliminate the deformity and rigidly fix the toe in a
      well-aligned position. Hammer-toe correction procedures can be performed with
      temporary Kirschner wire (K-wire) fixation for 3 to 6 weeks with high success
      rates. Pain relief with successful hammer-toe correction approaches 90%; patient
      satisfaction rates approximate 84%. Although complication rates are rare in most
      series, there remains a concern regarding exposed temporary K-wire fixation,
      which has led to the development of multiple permanent internal fixation options.

PMID- 29362038
TI  - Management of Metatarsalgia and Lesser Toe Deformities.

PMID- 29362039
TI  - 2018: The Year of Balance.

PMID- 29362040
TI  - A Daily Dose of Positive Perspective.

PMID- 29362041
TI  - Collaborative Development of a Perioperative Thermal Care Bundle Using the
      Guideline Implementability Appraisal Tool.
AB  - BACKGROUND: Perioperative hypothermia significantly increases a patient's risk of
      adverse complications, such as surgical site infection; morbid cardiac events,
      and surgical bleeding. Although guideline recommendations are relatively simple
      and inexpensive, they are often not adhered to in clinical practice. Knowledge
      tools are tangible resources that assist clinicians to provide evidence-based
      care. PURPOSE: This article reports the collaborative development of a knowledge
      tool-a perioperative thermal care bundle. DESIGN: Collaborative, iterative
      design. METHODS: A multidisciplinary panel of experts used the online GuideLine
      Implementability Appraisal tool to prioritize and select recommendations for
      inclusion in the care bundle. FINDINGS: Through a consensus process, the expert
      panel selected three main bundle elements: Assess patient's risk of hypothermia
      and contraindications to active warming; record temperature frequently
      preoperatively, intraoperatively, and postoperatively; and actively warm,
      intraoperatively, if they are at high risk, or anytime they are hypothermic.
      CONCLUSIONS: The GuideLine Implementability Appraisal tool was a simple yet
      comprehensive tool that enabled the development of a care bundle by expert
      clinicians.

PMID- 29362042
TI  - Implementing Microstream End-Tidal CO2 in the PACU.
AB  - Managing patients with undiagnosed Obstructive Sleep Apnea (OSA) can be a
      challenge in the postoperative phase. OSA is a chronic disease defined by pauses
      in breathing that are repetitive during sleep that can last for one minute or
      longer. This can occur more than five times in an hour. As many as 80-90% of
      patients undergoing elective surgery have undiagnosed sleep apnea and an
      increased risk of respiratory complications postoperatively. Capnography is a
      monitoring tool that can detect increases in end-tidal carbon dioxide levels,
      which is a sign of respiratory decline.

PMID- 29362043
TI  - Obstructive Sleep Apnea: Emphasis on Discharge Education After Surgery.
AB  - In the United States, the prevalence of obstructive sleep apnea (OSA) in the
      adult population is increasing. More than half of the surgical patients with OSA
      are predisposed to increased incidence of perioperative complications. Based on
      the recent evidence, obstructive events are at the highest on the third day after
      surgery, which predisposes them for postoperative complications. The American
      Society of Perianesthesia Nurses recommends that discharge education on OSA
      should be provided after surgery to patients diagnosed with OSA to promote
      continuous positive airway pressure (CPAP) compliance and self-care behaviors at
      home. However, CPAP adherence is poor. The purpose of this evidence-based
      practice project is to evaluate the effectiveness of discharge education on OSA
      for increasing CPAP compliance after surgery among adult surgical patients
      diagnosed with OSA, who use CPAP.

PMID- 29362044
TI  - Intrathecal Morphine-Related Perioperative Hypothermia in Women Undergoing
      Cesarean Delivery: A Retrospective Case-Control Study.
AB  - PURPOSE: Rates of inadvertent perioperative hypothermia among women undergoing
      spinal anesthesia for cesarean delivery are reported to be high. Intrathecal
      morphine has been noted to have a potentially potent effect on thermoregulation.
      This retrospective case-control study sought to investigate the incidence of
      perioperative hypothermia in women undergoing cesarean delivery with and without
      intrathecal morphine and to describe any clinical factors associated with the
      condition, the identification of which would provide direction for nursing
      priorities in the care of the condition. DESIGN: A retrospective case-controlled
      study design was used. METHODS: The charts of 358 women who had undergone
      emergency or elective cesarean delivery under spinal anesthesia were reviewed:
      179 having received intrathecal morphine and 179 having received spinal
      anesthesia without intrathecal morphine (control group). SPSS (IBM, Armonk, New
      York), version 22, was used for data analysis, including logistic regression to
      predict the outcome of hypothermia across the study population. FINDINGS: There
      was no significant difference (P = .62; 95% confidence interval, -0.09 to 0.15)
      in mean postoperative temperature for the morphine group (mean postanesthesia
      care unit arrival temperature, 35.91 degrees C; standard deviation, 0.59) and the
      no morphine group (mean postanesthesia care unit arrival temperature, 35.88
      degrees C; standard deviation, 0.52). However, within groups, the temperature
      decline preoperatively to postoperatively was statistically (and clinically)
      significant. CONCLUSIONS: The results refute the suggestion that intrathecal
      morphine contributes to greater core temperature decline in this population;
      however, it does confirm that perioperative hypothermia is a prevalent concern
      for women undergoing cesarean delivery and that pre-emptive measures should be
      routinely considered by health care providers.

PMID- 29362045
TI  - Postoperative Shivering Among Cannabis Users at a Public Hospital in Trinidad,
      West Indies.
AB  - PURPOSE: Postoperative shivering has been anecdotally observed to be frequent and
      severe in Cannabis smokers following general anesthesia in the Caribbean. The aim
      of this study was to compare the frequency and intensity of postoperative
      shivering in Cannabis users versus non-users. DESIGN: A prospective, cross
      sectional, observational design was used. METHODS: Demographic data were
      obtained. Patients were grouped into Cannabis users and non-users. All patients
      received standardized general anesthesia and were administered warmed fluids
      intraoperatively. Ambient room temperatures and clinical data were recorded.
      Patients' core body temperature was recorded at 10-minute intervals both in the
      operating room and the post-anesthesia care unit (PACU). Postoperatively an
      independent observer assessed the patients who had shivering using a scoring
      system ranging from 0 to 3. Treatment for shivering and post-treatment shivering
      scores were also recorded. FINDINGS: Fifty-five patients were studied, of which
      71% were male. There were 25 (45%) Cannabis users, of which 50% smoked < 5 joints
      per week, and 35% smoked >10 joints per week; 30 (55%) patients were non-users.
      The overall incidence of postoperative shivering was 36%; 16% had a shivering
      score of '3', 13% had '2' and 7% had a score of '1'. The incidence of
      postoperative shivering among Cannabis users was 40% while it was 33.3% in non
      users. Also, 90% of Cannabis users had shivering scores of 2 and 3, compared to
      70% of non-users. CONCLUSIONS: There was a higher incidence and intensity of
      shivering in Cannabis smokers, although the study could not establish a
      statistically significant difference in the frequency and severity of shivering
      between Cannabis users and non-users.

PMID- 29362046
TI  - The Efficacy of Intraoperative EEG to Predict the Occurrence of Emergence
      Agitation in the Postanesthetic Room After Sevoflurane Anesthesia in Children.
AB  - PURPOSE: Emergence agitation (EA) is common after sevoflurane anesthesia, but
      there are no definite predictors. This study investigated whether intraoperative
      electroencephalography (EEG) can indicate the occurrence of EA in children.
      DESIGN: A prospective predictive study design was used. METHODS: EEG-derived
      parameters (spectral edge frequency 95, beta, alpha, theta, and delta power) were
      measured at 1.0 minimum alveolar concentration (MAC) and 0.3 MAC of end-tidal
      sevoflurane (EtSEVO) in 29 patients. EA was evaluated using an EA score (EAS) in
      the postanesthetic care unit on arrival (EAS 0) and at 15 and 30 minutes after
      arrival (EAS 15 and EAS 30). The correlation between EEG-derived parameters and
      EAS was analyzed using Spearman correlation, and receiver-operating
      characteristic curve analysis was used to measure the predictability. FINDINGS:
      EA occurred in 11 patients. The alpha power at 1.0 MAC of EtSEVO was correlated
      with EAS 15 and EAS 30. The theta/alpha ratio at 0.3 MAC of EtSEVO was correlated
      with EAS 30. The area under the receiver-operating characteristic curve of
      percentage of alpha bands at 0.3 MAC of EtSEVO and the occurrence of EA was
      0.672. CONCLUSIONS: Children showing high-alpha powers and low theta powers (=
      low theta/alpha ratio) during emergence from sevoflurane anesthesia are at high
      risk of EA in the postanesthetic care unit.

PMID- 29362047
TI  - Impact of Dexmedetomidine on Pediatric Agitation in the Postanesthesia Care Unit.
AB  - PURPOSE: This study aims to investigate the impacts of dexmedetomidine (DEX) on
      agitation in the postanesthesia care unit (PACU) for pediatric patients
      undergoing tonsillectomy. DESIGN: Eighty-two pediatric patients with elective
      tonsillectomy were randomly divided into the DEX group (group D) and the control
      group (group C). All patients' surgery in the two study groups were completed
      under tracheal cannula-based general anesthesia. Group D was infused 0.2
      mcg/kg/hour DEX. The operation time, extubation time, PACU time, number of cases
      with nausea and vomiting, hemodynamic changes, and doses of rescue fentanyl, as
      well as every 10-minute observational pain scoring, and emergence agitation score
      in PACU, of the two groups were recorded. METHODS: Chi-square and Fischer exact
      tests were applied for categorical variables. FINDINGS: The maximum observational
      pain scoring and emergence agitation score of group D at 0, 10, and 20 minutes in
      PACU were significantly lower than group C (P < .01); the rescue doses of
      fentanyl and incidence of severe agitation in PACU in group D were significantly
      reduced than group C (P < .01). Group D showed significantly less cases with
      nausea and vomiting than group C (P < .05). CONCLUSIONS: Low-dose DEX could
      significantly reduce the delirium and agitation in the PACU stage of pediatric
      tonsillectomy, and there were no untoward hemodynamic events in this study of 80
      patients.

PMID- 29362048
TI  - Protective Nursing Advocacy: Translation and Psychometric Evaluation of an
      Instrument and a Descriptive Study of Swedish Registered Nurse Anesthetists'
      Beliefs and Actions.
AB  - PURPOSE: To translate and adapt the Protective Nursing Advocacy Scale (PNAS) into
      a Swedish version (PNAS-Swe), evaluate its psychometric properties, and describe
      registered nurse anesthetists' (RNAs) advocacy beliefs and actions from a
      protective perspective. DESIGN: A cross-sectional design was used. METHODS:
      First, the PNAS was translated into Swedish. Next, the content and construct
      validity of the PNAS four subscales was evaluated. Finally, the PNAS-Swe was used
      to describe Swedish RNA beliefs and actions regarding protective nursing
      advocacy. FINDINGS: The final PNAS-Swe has 29 items in four subscales. The RNAs
      reported that they feel that they should provide protective nursing advocacy for
      their patients. There were no differences in gender, or associations with age, or
      work experience regarding their advocacy beliefs or actions. CONCLUSIONS: The
      PNAS-Swe is valid for use in a Swedish context. Protective nursing advocacy is
      important to the RNAs, which is in congruence with earlier qualitative studies.

PMID- 29362049
TI  - Nurse Anesthetists' Reflections on Caring for Patients With Previous Substance
      Dependence: Balancing Between Professionalism and Preconceptions.
AB  - PURPOSE: The study aim was to describe nurse anesthetists' reflections on the
      provision of perioperative care to patients with previous substance dependence.
      DESIGN: A qualitative approach with a descriptive design. METHODS: Semistructured
      interviews based on clinical vignettes were conducted with 10 nurse anesthetists.
      FINDINGS: The perioperative care provided to patients with previous substance
      dependence was perceived as balancing between professionalism and preconceptions
      for this specific patient group. The nurse anesthetists felt that anesthetizing
      this group of patients constituted a challenge with regard to knowledge,
      experience, and time. However, the nurses also had feelings of distrust and
      uncertainty because of lack of knowledge. CONCLUSIONS: The nurse anesthetists
      strove to uphold the principle that patients who are/have been substance
      dependent have the same right to adequate treatment and care as all patients. If
      guidelines were developed for this patient group, care could be made safer and
      nurses' sense of uncertainty minimized.

PMID- 29362051
TI  - Tips, Tricks, and Techniques for Managing the Chronic Pain Patient in the
      Ambulatory Setting.

PMID- 29362050
TI  - Nurses' Experience of Patient Care in Multibed Hospital Rooms: Results From In
      Depth Interviews With Nurses After Further Education in Anesthesia.
AB  - PURPOSE: The purpose of this study was to investigate and explore nurse's
      previous experiences of patient care in MBRs before their further education in
      anesthesia. DESIGN: Qualitative research. METHODS: Data were collected through
      three focus group interviews using content data analysis. FINDINGS: Maintaining
      patient privacy, providing conditions for communication between health care
      professionals and patients, and undertaking daily practical care were stated as
      the main problems in MBR care. Inferior conditions for providing sensitive
      information and communication with proxies, especially in association with
      language problems, were frequently encountered. Patient's proxies could
      facilitate several problematic issues in MBR care. CONCLUSIONS: The present study
      characterized well-defined and easily recognizable clinical problems experienced
      in the care of patients in an MBR setting from a nurse's perspective. The opinion
      shared by most nurses was that the inability to implement privacy, dignity, and
      sound communication with patients should be taken into account in future hospital
      designs. General dissatisfaction with work environment, increased stress, and the
      risk of errors in care may otherwise follow.

PMID- 29362052
TI  - Daily Intentional Nurse Leader Rounding on Patients.

PMID- 29362053
TI  - Promoting Evidence-Based Practice and Dispelling Urban Legends to Achieve Safer
      Pain Management.

PMID- 29362054
TI  - Exercise and Positive Living in Human Immunodeficiency Virus/AIDS.
AB  - Evidence would suggest that regardless of disease status, people living with
      human immunodeficiency virus (HIV)/AIDS can obtain similar health benefits from
      routine physical activity reported within general populations. Research has shown
      significant improvements among psychological and physiologic variables within the
      first 5 to 6 weeks of beginning a routine physical activity program. Daily
      activity has shown promising results in other clinical populations, but there is
      still a paucity of research that limits evidence among the HIV population.
      Additional research is needed to examine the long-term benefits of physical
      activity, and to discover more practical ways to achieve this lifestyle change.

PMID- 29362055
TI  - Stigma and Discrimination: Threats to Living Positively with Human
      Immunodeficiency Virus.
AB  - Antiretroviral therapy and care advances have resulted in people with human
      immunodeficiency virus (HIV) living longer and enjoying a higher level of
      physical well-being. Despite such advances, individuals with HIV continue to
      confront challenges to living positively, including facing the secondary epidemic
      of stigma and discrimination. Following is a historical overview of the concept
      of stigma and an exploration of the causes and consequences of multilevel stigma
      for individuals with HIV. Strategies used by individuals and societies to manage
      stigma and avoid negative experiences also are examined.

PMID- 29362057
TI  - Nutritional Issues and Positive Living in Human Immunodeficiency Virus/AIDS.
AB  - Nutritional counseling has been shown to improve dietary intake in individuals
      with human immunodeficiency virus (HIV)/AIDS. Registered dietitians/nutritionists
      can individualize diet interventions to optimize effectiveness in treating
      metabolic consequences of the HIV infection or highly active antiretroviral
      therapy. Nutrition management for individuals infected with HIV can be helpful in
      maintaining lean body weight, combating oxidative stress, reducing complications
      from hyperglycemia and hyperlipidemia, and managing gastrointestinal function.
      Consideration should be given to including the expertise of a registered
      dietitian/nutritionist.

PMID- 29362056
TI  - End-of-Life Care and Bereavement Issues in Human Immunodeficiency Virus-AIDS.
AB  - This review article addresses end-of-life care issues characterizing human
      immunodeficiency virus progression by delineating associated stages of medical
      and nursing care. The initial progression from primary medical and nursing care
      aimed at functional cure to palliative care is discussed. This transition is
      considered in accord with the major symptoms experienced, including fatigue,
      pain, insomnia; decreased libido, hypogonadism, memory, and concentration;
      depression; and distorted body image. From the stage of palliative care,
      progression is delineated onward through the stages of hospice care, death and
      dying, and the subsequent bereavement process.

PMID- 29362058
TI  - The Role of Faith-Based Organizations in the Education, Support, and Services for
      Persons Living with Human Immunodeficiency Virus/Acquired Immunodeficiency
      Syndrome.
AB  - Faith-based organizations are in a unique position to provide resilience
      enhancing efforts for persons living with human immunodeficiency virus/AIDS. Many
      persons living with human immunodeficiency virus/AIDS report having a strong
      faith or religious affiliation, with a large percentage attending church services
      on a regular basis. Faith-based organizations can use these factors to reach out
      to these individuals and effectively promote health, well-being, education, and
      support. Faith-based organizations can contribute to the reduction of stigma and
      isolation for persons living with human immunodeficiency virus/AIDS.

PMID- 29362059
TI  - Mindful Living with Human Immunodeficiency Virus and AIDS: Behavioral Medicine
      for Patient Resilience and Improved Screening Practices.
AB  - Complementary techniques are useful in treating adverse symptoms of human
      immunodeficiency virus (HIV) and AIDS, and in preventing disease spread by
      encouraging screening. This study indicates that HIV diagnosis rates are higher
      in states where behavioral medicine is practiced; participation in such
      activities may influence the extent to which someone might closely monitor
      personal health. A strong evidence-base exists for the recommendation of
      mindfulness practices that improve rates of primary preventive practices and self
      reported quality of life for participants living with chronic conditions such as
      HIV and AIDS. Access to such programs is an area for future research and
      practice.

PMID- 29362060
TI  - Promoting Cardiovascular Health in Patients Living with Human Immunodeficiency
      Virus/Acquired Immunodeficiency Syndrome.
AB  - Patients living with human immunodeficiency virus/acquired immunodeficiency
      syndrome (PLWHA) are at increased risk of cardiovascular disease because of
      advances in human immunodeficiency virus/acquired immunodeficiency syndrome
      treatment and increased life expectancy. Cardiovascular health promotion in PLWHA
      includes strategies for risk factor reduction, disease prevention, early
      detection, and treatment of cardiovascular disease.

PMID- 29362061
TI  - Substance Use Disorders in People Living with Human Immunodeficiency Virus/AIDS.
AB  - Persons living with human immunodeficiency virus (HIV)/AIDS have a substantial
      burden of co-occurring substance use disorders (SUDs); untreated alcohol and drug
      use disorders among people living with HIV/AIDS contribute to worse HIV care
      outcomes. SUDs are associated with key health behaviors and outcomes, including
      delays in seeking medical care, poor engagement in treatment, reduced adherence
      to medical treatment and antiretroviral therapy, immunosuppression, increased HIV
      transmission through risky sexual behaviors, and increased burdens on health care
      systems. HIV infection comorbid with SUD and a psychiatric disorder is a
      clinically challenging condition creating a complex set of medical and
      psychosocial challenges.

PMID- 29362062
TI  - Best Practices and Self-Care to Support Women in Living Well with Human
      Immunodeficiency Virus/AIDS.
AB  - Women accounted for 20% of the cumulative AIDS cases in the United States as of
      2015. Although their incidence of human immunodeficiency virus (HIV) has declined
      in recent years, the rates of new infections and AIDS diagnoses for women of
      color have remained high. Women with HIV tend to be more vulnerable than men with
      this disease. They are more likely to be poor, uninsured, depressed, and
      homeless; to have experienced interpersonal violence; and to be caregivers.
      Attention to psychosocial needs and building trust are fundamental to engaging
      HIV-positive women in care and helping them attain optimal health.

PMID- 29362063
TI  - Management of Coinfections in Patients with Human Immunodeficiency Virus.
AB  - In addition to chronic use of antiretrovirals to maintain suppression of human
      immunodeficiency virus (HIV), many persons living with HIV are coinfected with
      tuberculosis, hepatitis B, or hepatitis C. These coinfections can be successfully
      treated or managed alongside HIV infection. Clinicians should follow practice
      guidelines to appropriately screen patients with HIV for these coinfections and
      initiate treatment when necessary. The most significant concern when treating any
      of these coinfections is to avoid drug-drug interactions with the patient's
      antiretrovirals. Several excellent practice guidelines exist for treatment of
      these common HIV coinfections.

PMID- 29362064
TI  - A Therapeutic Perspective of Living with Human Immunodeficiency Virus/AIDS in
      2017.
AB  - Patients with human immunodeficiency virus (HIV)/AIDS live a far different life
      today compared with those who were infected in the 1980s and 1990s.
      Antiretroviral therapy has evolved from a once poorly tolerated, heavy pill
      burden to the availability of many once-daily single-tablet regimens. The
      improvements in therapy have necessitated the need to be cognizant of
      comorbidities as well as drug-drug interactions. Despite the tremendous advances
      in therapy, newer therapies are in the pipeline and continue to emerge, making
      care for patients burdened by HIV perhaps easier than it has ever been.

PMID- 29362065
TI  - Positive Living with Human Immunodeficiency Virus/Acquired Immunodeficiency
      Syndrome.

PMID- 29362066
TI  - The Past, Present, and Future of Facial Fat Grafting.

PMID- 29362067
TI  - Fat Grafting in Facial Aesthetic Units.

PMID- 29362068
TI  - Autologous Fat Transfer for Facial Augmentation and Regeneration: Role of
      Mesenchymal Stem Cells.

PMID- 29362069
TI  - Fat Graft with Growth Factors.

PMID- 29362070
TI  - Autologous Fat Augmentation of the Face.

PMID- 29362071
TI  - Fat Grafting as an Adjunct to Facial Rejuvenation Procedures.

PMID- 29362072
TI  - Autologous Fat Transfer for Maxillofacial Reconstruction.

PMID- 29362073
TI  - Periorbital Rejuvenation with Application of Fat Transfer.

PMID- 29362074
TI  - Current Techniques in Fat Grafting.

PMID- 29362075
TI  - Complications in Fat Grafting.

PMID- 29362076
TI  - Fat Grafting: Challenges and Debates.

PMID- 29362078
TI  - Ectopic expression of SsPETE2, a plastocyanin from Suaeda salsa, improves plant
      tolerance to oxidative stress.
AB  - Accumulating evidence indicates that plant plastocyanin is involved in copper
      homeostasis, yet the physiological relevance remains elusive. In this study, we
      found that a plastocyanin gene (SsPETE2) from euhalophyte Suaeda salsa possessed
      a novel antioxidant function, which was associated with the copper-chelating
      activity of SsPETE2. In S. salsa, expression of SsPETE2 increased in response to
      oxidative stress and ectopic expression of SsPETE2 in Arabidopsis enhanced the
      antioxidant ability of the transgenic plants. SsPETE2 bound Cu ion and alleviated
      formation of hydroxyl radicals in vitro. Accordingly, SsPETE2 expression lowered
      the free Cu content that was associated with reduced H2O2 level under oxidative
      stress. Arabidopsis pete1 and pete2 mutants showed ROS-sensitive phenotypes that
      could be restored by expression of SsPETE2 or AtPETEs. In addition, SsPETE2
      expressing plants exhibited more potent tolerance to oxidative stress than plants
      overexpressing AtPETEs, likely owing to the stronger copper-binding activity of
      SsPETE2 than AtPETEs. Taken together, these results demonstrated that plant PETEs
      play a novel role in oxidative stress tolerance by regulating Cu homeostasis
      under stress conditions, and SsPETE2, as an efficient copper-chelating PETE,
      potentially could be used in crop genetic engineering.

PMID- 29362079
TI  - The many types of carbonic anhydrases in photosynthetic organisms.
AB  - Carbonic anhydrases (CAs) are enzymes that catalyze the interconversion of CO2
      and HCO3-. In nature, there are multiple families of CA, designated with the
      Greek letters alpha through theta. CAs are ubiquitous in plants, algae and
      photosynthetic bacteria, often playing essential roles in the CO2 concentrating
      mechanisms (CCMs) which enhance the delivery of CO2 to Rubisco. As algal CCMs
      become better characterized, it is clear that different types of CAs are playing
      the same role in different algae. For example, an alpha-CA catalyzes the
      conversion of accumulated HCO3- to CO2 in the green alga Chlamydomonas
      reinhardtii, while a theta-CA performs the same function in the diatom
      Phaeodactylum tricornutum. In this review we argue that, in addition to its role
      of delivering CO2 for photosynthesis, other metabolic roles of CA have likely
      changed as the Earth's atmospheric CO2 level decreased. Since the algal and plant
      lineages diverged well before the decrease in atmospheric CO2, it is likely that
      plant, algae and photosynthetic bacteria all adapted independently to the drop in
      atmospheric CO2. In light of this, we will discuss how the roles of CAs may have
      changed over time, focusing on the role of CA in pH regulation, how CAs affect
      CO2 supply for photosynthesis and how CAs may help in the delivery of HCO3- for
      other metabolic reactions.

PMID- 29362080
TI  - The miRNAome dynamics during developmental and metabolic reprogramming of tomato
      root infected with potato cyst nematode.
AB  - Cyst-forming plant-parasitic nematodes are pests threatening many crops. By means
      of their secretions cyst nematodes induce the developmental and metabolic
      reprogramming of host cells that lead to the formation of a syncytium, which is
      the sole food source for growing nematodes. The in depth micro RNA (miRNA)
      dynamics in the syncytia induced by Globodera rostochiensis in tomato roots was
      studied. The miRNAomes were obtained from syncytia covering the early and
      intermediate developmental stages, and were the subject of differential
      expression analysis. The expression of 1235 miRNAs was monitored. The fold change
      (log2FC) ranged from -7.36 to 8.38, indicating that this transcriptome fraction
      was very variable. Moreover, we showed that the DE (differentially expressed)
      miRNAs do not fully overlap between the selected time points, suggesting
      infection stage specific regulation by miRNA. The correctness of RNA-seq
      expression profiling was confirmed by qRT-PCR (quantitative Real Time Polymerase
      Chain Reaction) for seven miRNA species. Down- and up-regulated miRNA species,
      including their isomiRs, were further used to identify their potential targets.
      Among them there are a large number of transcription factors linked to different
      aspects of plant development belonging to gene families, such as APETALA2 (AP2),
      SQUAMOSA (MADS-box), MYB, GRAS, and AUXIN RESPONSE FACTOR (ARF). The substantial
      portion of potential target genes belong to the NB-LRR and RLK (RECEPTOR-LIKE
      KINASE) families, indicating the involvement of miRNA mediated regulation in
      defense responses. We also collected the evidence for target cleavage in the case
      of 29 miRNAs using one of three alternative methods: 5' RACE (5' Rapid
      Amplification of cDNA Ends), a search of tasiRNA within our datasets, and the
      meta-analysis of tomato degradomes in the GEO (Gene Expression Omnibus) database.
      Eight target transcripts showed a negative correlation with their respective
      miRNAs at two or three time points. These results indicate a large regulatory
      potential for miRNAs in tuning the development and defense responses.

PMID- 29362081
TI  - Genome-wide association studies of doubled haploid exotic introgression lines for
      root system architecture traits in maize (Zea mays L.).
AB  - Root system architecture (RSA) is becoming recognized as important for water and
      nutrient acquisition in plants. This study focuses on finding single nucleotide
      polymorphisms (SNPs) associated with seedling RSA traits from 300 doubled haploid
      (DH) lines derived from crosses between Germplasm Enhancement of Maize (GEM)
      accessions and inbred lines PHB47 and PHZ51. These DH lines were genotyped using
      62,077 SNP markers, while root and shoot phenotype data were collected from 14
      day old seedlings. Genome-wide association studies (GWAS) were conducted using
      three models to offset false positives/negatives. Multiple SNPs associated with
      seedling root traits were detected, some of which were within or linked to gene
      models that showed expression in seedling roots. Significant trait associations
      involving the SNP S5_152926936 on Chromosome 5 were detected in all three models,
      particularly the trait network area. The SNP is within the gene model
      GRMZM2G021110, which is expressed in roots at seedling stage. SNPs that were
      significantly associated with seedling root traits, and closely linked to gene
      models that encode proteins associated with root development were also detected.
      This study shows that the GEM-DH panel may be a source of allelic diversity for
      genes controlling seedling root development.

PMID- 29362082
TI  - Molecular characterization of a double-flower mutation in Matthiola incana.
AB  - The double flower is one of the most important traits in the floricultural plant
      Matthiola incana. Although a "doubleness" locus (S/s) was defined by genetic
      analysis a century ago, the gene responsible for double flowers has not been
      identified in M. incana. We isolated MiAG from M. incana cultivars, and its
      sequence and genomic structure were found to be highly similar to the AGAMOUS
      gene in Arabidopsis. Two independent mutated alleles miag1 and miag2 were
      identified from the double-flowered individuals of M. incana cultivars. Deletions
      of 135 bp (from the 2nd exon to the 2nd intron) and 89 bp (from the 7th intron to
      the 8th exon) were detected in miag1 and miag2, respectively. No transcript was
      detected in flower buds from miag1 alleles in corresponding cultivars, whereas
      three mRNA variants with frameshifts were transcribed from the miag2 allele in
      other cultivars. Thus, two mutated alleles corresponding to the s locus
      contributed to the 'eversporting' type double-flower cultivars in M. incana.
      Moreover, we also developed co-dominant molecular markers to describe the
      genotypes of the three alleles of MiAG. Using these DNA markers allows for
      selection of single- or double-flowered individuals among seedlings that do not
      display phenotypic differences.

PMID- 29362083
TI  - Functional characterization of a heterologously expressed Brassica napus WRKY41-1
      transcription factor in regulating anthocyanin biosynthesis in Arabidopsis
      thaliana.
AB  - Previous studies have shown that a plant WRKY transcription factor, WRKY41, has
      multiple functions, and regulates seed dormancy, hormone signaling pathways, and
      both biotic and abiotic stress responses. However, it is not known about the
      roles of AtWRKY41 from the model plant, Arabidopsis thaliana, and its ortholog,
      BnWRKY41, from the closely related and important oil-producing crop, Brassica
      napus, in the regulation of anthocyanin biosynthesis. Here, we found that the
      wrky41 mutation in A. thaliana resulted in a significant increase in anthocyanin
      levels in rosette leaves, indicating that AtWRKY41 acts as repressor of
      anthocyanin biosynthesis. RNA sequencing and quantitative real-time PCR analysis
      revealed increased expression of three regulatory genes AtMYB75, AtMYB111, and
      AtMYBD, and two structural genes, AT1G68440 and AtGSTF12, all of which contribute
      to anthocyanin biosynthesis, in the sixth rosette leaves of wrky41-2 plants at 20
      days after germination. We cloned the full length complementary DNA of BnWRKY41-1
      from the C2 subgenome of the B. napus genotype Westar and observed that, when
      overexpressed in tobacco leaves as a fusion protein with green fluorescent
      protein, BnWRKY41-1 is localized to the nucleus. We further showed that
      overexpression of BnWRKY41-1 in the A. thaliana wrky41-2 mutant rescued the
      higher anthocyanin content phenotype in rosette leaves of the mutant. Moreover,
      the elevated expression levels in wrky41-2 rosette leaves of several important
      regulatory and structural genes regulating anthocyanin biosynthesis were not
      observed in the BnWRKY41-1 overexpressing lines. These results reveal that
      BnWRKY41-1 has a similar role with AtWRKY41 in regulating anthocyanin
      biosynthesis when overexpressed in A. thaliana. This gene represents a promising
      target for genetically manipulating B. napus to increase the amounts of
      anthocyanins in rosette leaves.

PMID- 29362084
TI  - An ultraviolet B condition that affects growth and defense in Arabidopsis.
AB  - Ultraviolet B light (UV-B, 280-315 nm) is the shortest wavelength of the solar
      spectrum reaching the surface of the Earth. It has profound effects on plants,
      ranging from growth regulation to severe metabolic changes. Low level UV-B mainly
      causes photomorphogenic effects while higher levels can induce stress, yet these
      effects tend to overlap. Here we identified a condition that allows growth
      reduction without obvious detrimental stress in wild type Arabidopsis rosette
      plants. This condition was used to study the effects of a daily UV-B dose on
      plant characteristics of UV-B adapted plants in detail. Exploration of the
      transcriptome of developing leaves indicated downregulation of genes involved in
      stomata formation by UV-B, while at the same time genes involved in
      photoprotective pigment biosynthesis were upregulated. These findings correspond
      with a decreased stomatal density and increased UV-B absorbing pigments. Gene
      ontology analysis revealed upregulation of defense related genes and meta
      analysis showed substantial overlap of the UV-B regulated transcriptome with
      transcriptomes of salicylate and jasmonate treated as well as herbivore exposed
      plants. Feeding experiments showed that caterpillars of Spodoptera littoralis are
      directly affected by UV-B, while performance of the aphid Myzus persicae is
      diminished by a plant mediated process.

PMID- 29362085
TI  - Nitric oxide synthase in plants: The surprise from algae.

PMID- 29362086
TI  - The effects of putrescine are partly overlapping with osmotic stress processes in
      wheat.
AB  - Polyamine metabolism is in relation with several metabolic pathways and linked
      with plant hormones or signalling molecules; in addition polyamines may modulate
      the up- or down-regulation of gene expression. However the precise mechanism by
      which polyamines act at the transcription level is still unclear. In the present
      study the modifying effect of putrescine pre-treatment has been investigated
      using the microarray transcriptome profile analysis under the conditions where
      exogenous putrescine alleviated osmotic stress in wheat plants. Pre-treatment
      with putrescine induced the unique expression of various general stress-related
      genes. Although there were obvious differences between the effects of putrescine
      and polyethylene glycol treatments, there was also a remarkable overlap between
      the effects of putrescine and osmotic stress responses in wheat plants,
      suggesting that putrescine has already induced acclimation processes under
      control conditions. The fatty acid composition in certain lipid fractions and the
      antioxidant enzyme activities have also been specifically changed under osmotic
      stress conditions or after treatment with putrescine.

PMID- 29362087
TI  - Mutations in the MIT3 gene encoding a caroteniod isomerase lead to increased
      tiller number in rice.
AB  - Carotenoids not only play important roles in light harvesting and photoprotection
      against excess light, but also serve as precursors for apocaroteniod hormones
      such as abscisic acid (ABA) and strigolactones (SLs). Although light- and ABA
      associated phenotypes of the carotenoid biosynthesis mutants such as albino, leaf
      variegation and preharvest sprouting have been studied extensively, the SLs
      related branching phenotype is rarely explored. Here we characterized four
      allelic rice mutants named mit3, which exhibited moderately increased tiller
      number, semi-dwarfism and leaf variegation. Map-based cloning revealed that MIT3
      encodes a carotenoid isomerase (CRTISO), the key enzyme catalyzing the conversion
      from prolycopene to all-trans-lycopene in carotenoid biosynthesis. Prolycopene
      was accumulated while all-trans-lycopene was barely detectable in the dark-grown
      mit3 seedlings. Accordingly, content of lutein and beta-carotene, the two most
      abundant carotenoids, was significantly reduced. Furthermore, content of epi-5DS,
      a native SL, was significantly reduced in mit3. Exogenously applied GR24, a
      synthetic SL, could rescue the tillering phenotype of mit3. Double mutant
      analysis of mit3 with the SLs biosynthesis mutant d17 revealed that MIT3 controls
      tiller development upstream of the SLs biosynthesis pathway. Our results reveal
      that the tillering phenotype of mit3 is due to SL deficiency and directly link
      carotenoid deficiency with SL-regulated rice tillering.

PMID- 29362088
TI  - Emerging microbial biocontrol strategies for plant pathogens.
AB  - To address food security, agricultural yields must increase to match the growing
      human population in the near future. There is now a strong push to develop low
      input and more sustainable agricultural practices that include alternatives to
      chemicals for controlling pests and diseases, a major factor of heavy losses in
      agricultural production. Based on the adverse effects of some chemicals on human
      health, the environment and living organisms, researchers are focusing on
      potential biological control microbes as viable alternatives for the management
      of pests and plant pathogens. There is a growing body of evidence that
      demonstrates the potential of leaf and root-associated microbiomes to increase
      plant efficiency and yield in cropping systems. It is important to understand the
      role of these microbes in promoting growth and controlling diseases, and their
      application as biofertilizers and biopesticides whose success in the field is
      still inconsistent. This review focusses on how biocontrol microbes modulate
      plant defense mechanisms, deploy biocontrol actions in plants and offer new
      strategies to control plant pathogens. Apart from simply applying individual
      biocontrol microbes, there are now efforts to improve, facilitate and maintain
      long-term plant colonization. In particular, great hopes are associated with the
      new approaches of using "plant-optimized microbiomes" (microbiome engineering)
      and establishing the genetic basis of beneficial plant-microbe interactions to
      enable breeding of "microbe-optimized crops".

PMID- 29362089
TI  - Review: "Pyrophosphate and pyrophosphatases in plants, their involvement in
      stress responses and their possible relationship to secondary metabolism".
AB  - Pyrophosphate (PPi) is produced as byproduct of biosynthesis in the cytoplasm,
      nucleus, mitochondria and chloroplast, or in the tonoplast and Golgi by membrane
      bound H+-pumping pyrophosphatases (PPv). Inorganic pyrophosphatases (E.C.
      3.6.1.1; GO:0004427) impulse various biosynthetic reactions by recycling PPi and
      are essential to living cells. Soluble and membrane-bound enzymes of high
      specificity have evolved in different protein families and multiple
      pyrophosphatases are encoded in all plant genomes known to date. The soluble
      proteins are present in cytoplasm, extracellular space, inside chloroplasts, and
      perhaps inside mitochondria, nucleus or vacuoles. The cytoplasmic isoforms may
      compete for PPi with the PPv enzymes and how PPv and soluble activities are
      controlled is currently unknown, yet the cytoplasmic PPi concentration is high
      and fairly constant. Manipulation of the PPi metabolism impacts primary
      metabolism and vice versa, indicating a tight link between PPi levels and
      carbohydrate metabolism. These enzymes appear to play a role in germination,
      development and stress adaptive responses. In addition, the transgenic
      overexpression of PPv has been used to enhance plant tolerance to abiotic stress,
      but the reasons behind this tolerance are not completely understood. Finally, the
      relationship of PPi to stress suggest a currently unexplored link between PPi and
      secondary metabolism.

PMID- 29362090
TI  - Nerolidol production in agroinfiltrated tobacco: Impact of protein stability and
      membrane targeting of strawberry (Fragraria ananassa) NEROLIDOL SYNTHASE1.
AB  - The sesquiterpene alcohol nerolidol, synthesized from farnesyl diphosphate (FDP),
      mediates plant-insect interactions across multiple trophic levels with major
      implications for pest management in agriculture. We compared nerolidol
      engineering strategies in tobacco using agroinfiltration to transiently express
      strawberry (Fragraria ananassa) linalool/nerolidol synthase (FaNES1) either at
      the endoplasmic reticulum (ER) or in the cytosol as a soluble protein. Using
      solid phase microextraction and gas chromatography-mass spectrometry (SPME-GCMS),
      we have determined that FaNES1 directed to the ER via fusion to the transmembrane
      domain of squalene synthase or hydroxymethylglutaryl - CoA reductase displayed
      significant improvements in terms of transcript levels, protein accumulation, and
      volatile production when compared to its cytosolic form. However, the highest
      levels of nerolidol production were observed when FaNES1 was fused to GFP and
      expressed in the cytosol. This SPME-GCMS method afforded a limit of detection and
      quantification of 1.54 and 5.13 pg, respectively. Nerolidol production levels,
      which ranged from 0.5 to 3.0 MUg/g F.W., correlated more strongly to the
      accumulation of recombinant protein than transcript level, the former being
      highest in FaNES-GFP transfected plants. These results indicate that while the ER
      may represent an enriched source of FDP that can be exploited in metabolic
      engineering, protein accumulation is a better predictor of sesquiterpene
      production.

PMID- 29362091
TI  - Arabidopsis NAP-related proteins (NRPs) contribute to the coordination of plant
      growth, developmental rate, and age-related pathogen resistance under short days.
AB  - Plant nucleosome assembly protein-related proteins (NRPs) are histone chaperons
      involved in nucleosome turnover. Despite this basic cellular function, the
      Arabidopsis nrp1-1 nrp2-1 knock out mutant has been reported to exhibit only mild
      seedling root phenotypes and to significantly affect the expression of only few
      hundred genes Zhu et al. (2006). Here we report that NRP loss-of-function as well
      as the ectopic overexpression of At NRP1 significantly affected the growth,
      development, and the pathogen response of Arabidopsis plants under short day
      conditions. The nrp1-1 nrp2-1 mutant grew faster and flowered weeks earlier than
      the wild type and the overexpressor. The latter developed slower and flowered at
      a lower number of leaves than the mutant and the wild type. Moreover, the mutant
      was more sensitive, the overexpressor was more tolerant to pathogen-induced
      necrosis correlating with their more adult and juvenile character, respectively.
      Transcriptomic comparison of mature non-bolting plants agreed with the
      phenotypes. The presented and other published data indicate that although NRPs
      might not be absolutely required for normal plant growth and development, their
      level needs to be controlled to allow the epigenetic coordination of metabolic,
      growth, defence and developmental processes during the acclimation to
      unfavourable growth conditions such as short days.

PMID- 29362092
TI  - Can-miRn37a mediated suppression of ethylene response factors enhances the
      resistance of chilli against anthracnose pathogen Colletotrichum truncatum L.
AB  - Pepper anthracnose, caused by Colletotrichum species complex is the most
      destructive disease of chilli (Capsicum annuum L.). miRNAs are key modulators of
      transcriptional and post- transcriptional expression of genes during defense
      responses. In the present study, we performed a comparative miRNA profiling of
      susceptible (Arka Lohit-AL) and resistant (Punjab Lal-PL) chilli cultivars to
      identify 35 differentially expressed miRNAs that could be classified as positive,
      negative or basal regulators of defense against C. truncatum, the most potent
      anthracnose pathogen. Interestingly, a novel microRNA can-miRn37a was
      significantly induced in PL but largely repressed in AL genotype post pathogen
      attack. Subsequent over-expression of can-miRn37a in AL showed enhanced
      resistance to anthracnose, as evidenced by decreased fungal growth and induced
      expression of defense-related genes. Consequently, the expression of its three
      target genes encoding the ethylene response factors (ERFs) was down-regulated in
      PL as well as in the over-expression lines of AL genotypes. The ability of these
      targets to be regulated by can-miRn37a was further confirmed by transient co
      expression in Nicotiana benthamiana. Additionally, the virus-induced silencing of
      the three targets in the susceptible AL cultivar revealed their role in fungal
      colonization and induction of C. truncatum pathogenicity in chilli. Taken
      together, our study suggests that can-miRn37a provides a potential miRNA mediated
      approach of engineering anthracnose resistance in chilli by repressing ERFs and
      preventing fungal colonization.

PMID- 29362093
TI  - Functional characterization of naturally occurring wild soybean mutant (sg-5)
      lacking astringent saponins using whole genome sequencing approach.
AB  - Triterpenoid saponins are one of the most highly accumulated groups of functional
      components in soybean (Glycine max) and the oxidative reactions during their
      biosynthesis are required for their aglycone diversity. Natural mutants of
      soyasaponins in wild soybean (Glycine soja) are valuable resources for
      establishing the soyasaponin biosynthesis pathway and breeding new soybean
      varieties. In this study, we investigated the genetic mechanism behind the
      absence of group A saponins in a Korean wild soybean mutant, CWS5095. Whole
      genome sequencing (WGS) of CWS5095 identified four point mutations [Val6 -> Asp,
      Ile231 -> Thr, His294 -> Gln, and Arg376 -> Lys] in CYP72A69 (Glyma15g39090),
      which oxygenate the C-21 position of soyasapogenol B or other intermediates to
      produce soyasapogenol A, leading to group A saponin production. An in vitro
      enzyme activity assay of single-sited mutated clones indicated that the Arg376 >
      Lys mutation (a highly conserved mutation based on a nucleotide change from G ->
      A at the 1,127th position) may lead to loss of gene function in the sg-5 mutant.
      A very high normalized expression value of 377 reads per kilo base per million
      (RPKM) of Glyma15g39090 in the hypocotyl axis at the early maturation seed
      development stage confirmed their abundant presence in seed hypocotyls. A
      molecular dynamics analysis of the Arg376 > Lys mutation based on the CYP3A4 (a
      human CYP450) protein structure found that it was responsible for the increase in
      axis length toward the heme (active site), which is critically important for
      biological activity and ligand binding. Our results provide important information
      on how to eradicate bitter and astringent saponins in soybean by utilizing the
      reported mutation in Glyma15g39090, and its importance for seed hypocotyl
      development based on transcript abundance.

PMID- 29362094
TI  - Regulation of plant height in rice by the Polycomb group genes OsEMF2b, OsFIE2
      and OsCLF.
AB  - An ideal plant height is essential for crop yield. Some Polycomb group (PcG)
      genes mutants exhibit a dwarf phenotype in rice. To determine how PcG genes
      regulate plant height, we investigated the phenotypes of the emf2b mutant and
      OsEMF2b, OsFIE2 and OsCLF RNAi transgenic plants; they all exhibited dwarf
      phenotype. Further analyses indicated that stem elongation at jointing stage was
      seriously inhibited in emf2b and RNAi transgenic plants. Reduced cell expansion
      and cell division of stem caused significant reduction of stem length during
      mature period of OsEMF2b, OsFIE2 and OsCLF RNAi transgenic plants. Transcription
      analysis revealed that cell division, cell expansion and plant hormones related
      genes differentially expressed between emf2b and WT. In addition, PcG genes
      mutants weakened GA signal and GA concentration and leaded to suppresseion of
      plant height. Analysis of differentially expressed genes revealed that 109 up
      regulated and 19 down-regulated genes were identified in both emf2b and fie2.
      H3K27me3-modified sites were observed in 95 of the 109 up-regulated genes, and
      some of them were up-regulated in OsFIE2, OsCLF and OsEMF2b RNAi transgenic
      plants, and their H3K27me3 levels were reduced in emf2b. Moreover, OsEMF2b
      interacted with OsCLF. Therefore, we speculated that these PcG genes, OsFIE2,
      OsCLF and OsEMF2b, may work as a PRC2 to regulate rice height.

PMID- 29362095
TI  - The newly identified heat-stress sensitive albino 1 gene affects chloroplast
      development in rice.
AB  - High temperature, a major abiotic stress, significantly affects the yield and
      quality of crops in many parts of the world. Components of the photosynthetic
      apparatus are highly susceptible to thermal damage. Although the responses to
      acute heat stress have been studied intensively, the mechanisms that regulate
      chloroplast development under heat stress remain obscure, especially in crop
      plants. Here, we cloned and characterized the gene responsible for the heat
      sensitive albino1 (hsa1) mutation in rice (Oryza sativa). The hsa1 mutant harbors
      a recessive mutation in a gene encoding fructokinase-like protein2 (FLN2); the
      mutation causes a premature stop codon and results in a severe albino phenotype,
      with defects in early chloroplast development. The color of hsa1 mutant plants
      gradually changed from albino to green at later stages of development at various
      temperatures and chloroplast biogenesis was strongly delayed at high temperature
      (32  degrees C). HSA1 expression was strongly reduced in hsa1 plants compared to
      wild type (WT). HSA1 localizes to the chloroplast and regulates chloroplast
      development. An HSA1 deletion mutant induced by CRISPR/Cas9 was heat sensitive
      but had a faster greening phenotype than the original hsa1 allele at all
      temperatures. RNA and protein levels of plastid-encoded RNA polymerase-dependent
      plastid genes were markedly reduced in hsa1 plants compared to WT. These results
      demonstrated that HSA1 plays important roles in chloroplast development at early
      stages, and functions in protecting chloroplasts under heat stress at later
      stages in rice.

PMID- 29362096
TI  - Ectopic expression of Arabidopsis broad-spectrum resistance gene RPW8.2 improves
      the resistance to powdery mildew in grapevine (Vitis vinifera).
AB  - Powdery mildew is the most economically important disease of cultivated
      grapevines worldwide. Here, we report that the Arabidopsis broad-spectrum disease
      resistance gene RPW8.2 could improve resistance to powdery mildew in Vitis
      vinifera cv. Thompson Seedless. The RPW8.2-YFP fusion gene was stably expressed
      in grapevines from either the constitutive 35S promoter or the native promoter
      (NP) of RPW8.2. The grapevine shoots and plantlets transgenic for 35S::RPW8.2-YFP
      showed reduced rooting and reduced growth at later development stages in the
      absence of any pathogens. Infection tests with an adapted grapevine powdery
      mildew isolate En NAFU1 showed that hyphal growth and sporulation were
      significantly restricted in transgenic grapevines expressing either of the two
      constructs. The resistance appeared to be attributable to the ectopic expression
      of RPW8.2, and associated with the enhanced encasement of the haustorial complex
      (EHC) and onsite accumulation of H2O2. In addition, the RPW8.2-YFP fusion protein
      showed focal accumulation around the fungal penetration sites. Transcriptome
      analysis revealed that ectopic expression of RPW8.2 in grapevines not only
      significantly enhanced salicylic acid-dependent defense signaling, but also
      altered expression of other phytohormone-associated genes. Taken together, our
      results indicate that RPW8.2 could be utilized as a transgene for improving
      resistance against powdery mildew in grapevines.

PMID- 29362097
TI  - Raising orphans from a metadata morass: A researcher's guide to re-use of public
      'omics data.
AB  - More than 15 petabases of raw RNAseq data is now accessible through public
      repositories. Acquisition of other 'omics data types is expanding, though most
      lack a centralized archival repository. Data-reuse provides tremendous
      opportunity to extract new knowledge from existing experiments, and offers a
      unique opportunity for robust, multi-'omics analyses by merging metadata
      (information about experimental design, biological samples, protocols) and data
      from multiple experiments. We illustrate how predictive research can be
      accelerated by meta-analysis with a study of orphan (species-specific) genes.
      Computational predictions are critical to infer orphan function because their
      coding sequences provide very few clues. The metadata in public databases is
      often confusing; a test case with Zea mays mRNA seq data reveals a high
      proportion of missing, misleading or incomplete metadata. This metadata morass
      significantly diminishes the insight that can be extracted from these data. We
      provide tips for data submitters and users, including specific recommendations to
      improve metadata quality by more use of controlled vocabulary and by metadata
      reviews. Finally, we advocate for a unified, straightforward metadata submission
      and retrieval system.

PMID- 29362098
TI  - Protein degradation mechanisms modulate abscisic acid signaling and responses
      during abiotic stress.
AB  - Abiotic stresses such as salinity, drought, high temperature or freezing can be
      perceived, in part, as a transient or permanent hyperosmotic stress by the plant
      cell. As sessile organisms, the detrimental effects of these environmental
      insults limit plants productivity but also their geographical distribution.
      Sensing and signaling events that detect the hyperosmotic (or simply osmotic)
      stress involve the cellular increase of active abscisic acid (ABA). The stress
      phytohormone ABA regulates fundamental growth and developmental processes in the
      plant by marshalling metabolic and gene-expression reprogramming. Among the ABA
      responsive genes, some are strictly ABA-dependent in that their expression is
      almost undetectable in absence of elevated levels of cellular ABA, thus their
      physiological role may be required only transiently. In addition, ABA-dependent
      modulation of some of the signaling effectors can be irreversible. In this
      review, without any pretention to being exhaustive, we use specific examples to
      illustrate how mechanistically conserved eukaryotic cell proteolytic pathways
      affect ABA-dependent signaling. We describe how defined proteolysis mechanisms in
      the plant cell, including Regulated Intramembrane Proteolysis (RIP), the
      Ubiquitin 26S Proteasomal System (UPS), the endocytic and autophagy pathways,
      contribute to regulate the spatiotemporal level and activity of PP2Cs (protein
      phosphatases 2C), and how an intriguing ABA-induced protein, the plant
      Translocator protein (TSPO), is targeted for degradation. Degradation of
      regulatory or effector molecules modulates or desensitizes ABA-dependent
      signaling and reestablishes cellular homeostasis.

PMID- 29362099
TI  - Involvement of NR and PM-NR in NO biosynthesis in cucumber plants subjected to
      salt stress.
AB  - Nitrate reductase (NR) mainly reduces nitrate to nitrite. However, in certain
      conditions it can reduce nitrite to NO. In plants, a plasma membrane-associated
      form of NR (PM-NR) is present. It produces NO2- for nitrite NO/reductase (Ni
      NOR), which can release NO into the apoplastic space. The effect of 50 mM NaCl on
      NO formation and the involvement of NR in NO biosynthesis were studied in
      cucumber seedling roots under salt stress. In salt-stressed roots, the amount of
      NO was higher than in control. The application of tungstate abolished the
      increase of NO level in stressed roots, indicating that NR was responsible for NO
      biosynthesis under the test conditions. The involvement of other molybdoenzymes
      was excluded using specific inhibitors. Furthermore, higher cNR and PM-NR
      activities were observed in NaCl-treated roots. The increase in NR activity was
      due to the stimulation of CsNR genes expression and posttranslational
      modifications, such as enzyme dephosphorylation. This was confirmed by Western
      blot analysis. Moreover, the increase of nitrite tissue level in short-term
      stressed roots and the nitrite/nitrate ratio, with a simultaneous decrease of
      nitrite reductase (NiR) activity, in both short- and long-term stressed roots,
      could promote the production of NO by NR in roots under salt stress.

PMID- 29362100
TI  - The Jasmonate ZIM-domain protein gene SlJAZ2 regulates plant morphology and
      accelerates flower initiation in Solanum lycopersicum plants.
AB  - JAZ (Jasmonate ZIM-domain) proteins are important repressors in JA signaling
      pathway. JAZs were proved taking part in various development processes and
      resistance to biotic and abiotic stresses in Arabiodopsis. However, in tomato,
      the functional study of JAZs is rare, especially on plant growth and development.
      Here, a typical tomato JAZ gene, SlJAZ2 was isolated. Tomato plants
      overexpressing SlJAZ2 exhibited quicker leaf initiation, reduced plant height and
      internode length, decreasing trichomes, earlier lateral bud emergence and
      advanced flowering transition. Further experiments showed that the pith cells in
      transgenic plant stem were much smaller than wild-type and the genes related to
      cell elongation and gibberellin biosynthesis were down-regulated. Genes mediating
      trichome formation were also inhibited in plant stem epidermis. In addition, the
      flower initiation of transgenic plants were earlier and genes controlling
      flowering time were up-regulated significantly after SlJAZ2 was overexpressed.
      Our research demonstrates that SlJAZ2 accelerates the transition from vegetative
      growth to reproductive growth.

PMID- 29362102
TI  - Genomic relationships reveal significant dominance effects for growth in hybrid
      Eucalyptus.
AB  - Non-additive genetic effects can be effectively exploited in control-pollinated
      families with the availability of genome-wide markers. We used 41,304 SNP markers
      and compared pedigree vs. marker-based genetic models by analysing height,
      diameter, basic density and pulp yield for Eucalyptus urophylla * E.grandis
      control-pollinated families represented by 949 informative individuals. We
      evaluated models accounting for additive, dominance, and first-order epistatic
      interactions (additive by additive, dominance by dominance, and additive by
      dominance). We showed that the models can capture a large proportion of the
      genetic variance from dominance and epistasis for growth traits as those
      components are typically not independent. We also showed that we could partition
      genetic variances more precisely when using relationship matrices derived from
      markers compared to using only pedigree information. In addition, phenotypic
      prediction accuracies were only slightly increased by including dominance effects
      for growth traits since estimates of non-additive variances yielded rather high
      standard errors. This novel result improves our current understanding of the
      architecture of quantitative traits and recommends accounting for dominance
      variance when developing genomic selection strategies in hybrid Eucalyptus.

PMID- 29362101
TI  - Tempranillo clones differ in the response of berry sugar and anthocyanin
      accumulation to elevated temperature.
AB  - The intra-varietal genetic diversity of grapevine (Vitis vinifera L.) may be
      exploited to maintain grape quality under future warm conditions, which may alter
      grape berry development and composition. The present study assesses the effects
      of elevated temperature on the development of berry, grape composition and
      anthocyanins:sugars ratio of thirteen clones of V. vinifera. cv. Tempranillo that
      differed in length of the ripening period (time from veraison to berry total
      soluble solids, mainly sugars, of ca. 22  degrees Brix). Two temperature regimes
      (24  degrees C/14  degrees C or 28  degrees C/18  degrees C, day/night) were
      imposed to grapevine fruit-bearing cuttings from fruit set to maturity under
      greenhouse-controlled conditions. Elevated temperature hastened berry
      development, with a greater influence before the onset of ripening, and reduced
      anthocyanin concentration, colour intensity and titratable acidity. The clones
      significantly differed in the number of days that elapsed between fruit set and
      maturity. At the same concentration of total soluble solids, the anthocyanin
      concentration was lower at 28  degrees C/18  degrees C than 24  degrees C/14 
      degrees C, indicating a decoupling effect of elevated temperature during berry
      ripening. Thermal decoupling was explained by changes in the relative rate of
      response of anthocyanin and sugar build-up, rather than delayed onset of
      anthocyanin accumulation. Clones differed in the degree of thermal decoupling,
      but it was directly associated with differences neither in the length of their
      ripening period nor in plant vigour.

PMID- 29362103
TI  - Arabidopsis galactinol synthases 1 (AtGOLS1) negatively regulates seed
      germination.
AB  - Seed germination begins the growth phases of plants and its rate is affected not
      only by plant hormones, including abscisic acid (ABA), gibberellin (GA) and
      brassinosteroids (BRs), but also by environmental factors. In this study, we
      searched for additional chemical reagents that affect seed germination, using the
      det2-1 and ga1-3 mutants that showed reduced seed germination due to defective BR
      or GA- biosynthesis, respectively. We found that the reducing reagent
      dithiothreitol (DTT) specifically enhanced seed germination of det2-1 compared
      with that of ga1-3. To further investigate the underlying molecular mechanism for
      this phenomenon, we identified AtGOLS1 as a differentially expressed gene in
      germinating seeds treated with DTT by GeneFishing analysis. AtGOLS1 encodes a
      galactinol synthase, critical for the first step in raffinose family
      oligosaccharides synthesis during seed maturation. We observed that expression of
      AtGOLS1 decreased when conditions were favorable for seed germination. We also
      determined that the seed germination rate was faster in T-DNA knockout atgols1
      mutant and transgenic plants transformed with an RNA interference construct
      targeting AtGOLS1 compared with wild type plants. The double mutant of det2-1 and
      atgols1 also suppressed the reduced seed germination of the det2-1. Taken
      together, our results suggest that AtGOLS1 acts as a negative regulator in seed
      germination.

PMID- 29362104
TI  - Polypharmacy: What About Undertreated Medication-Induced Hypothyroidism?

PMID- 29362106
TI  - Reply.

PMID- 29362105
TI  - Wisely Choosing: Aging, Precision, and Medicine.

PMID- 29362107
TI  - Impact of Observation Hospitalizations on Low-Income Medicare Beneficiaries.

PMID- 29362108
TI  - The Reply.

PMID- 29362109
TI  - Migraine Headache and Long-Term Cardiovascular Outcomes: Methodological Issues.

PMID- 29362110
TI  - The Reply.

PMID- 29362111
TI  - Evaluation of the Yale New Haven Readmission Risk Score for Pneumonia in a
      General Hospital Population: Methodologic Issues.

PMID- 29362112
TI  - The Reply.

PMID- 29362113
TI  - Hepatocellular Carcinoma Screening in Patients Treated for Hepatitis C.

PMID- 29362114
TI  - Compositional and functional variations of oral microbiota associated with the
      mutational changes in oral cancer.
AB  - OBJECTIVES: Both genetic and environmental factors are conceivably required to
      assess the prognosis of oral squamous cell carcinoma (OSCC), yet little is known
      regarding the relationship between oral microbiome and the mutational spectrum of
      OSCC. MATERIALS AND METHODS: Here, we used 16S rRNA amplicon sequencing to study
      the composition of oral microorganisms in OSCC patients, whose cancer mutational
      profiles were previously defined by whole-exome sequencing, to evaluate the
      relationship between oral microbiome and the mutational changes in OSCC. RESULTS:
      Analyzing the contributions of the five mutational signatures extracted from the
      primary tumors revealed three groups of OSCC (mutational signature cluster, MSC1
      3) that were significantly associated with demographic and clinical features.
      Taxonomic analysis of the predominant phyla in salivary samples showed variation
      in the relative abundance of Firmicutes and Bacteroidetes in the three MSC
      groups. In addition, significant differences in bacterial species richness (alpha
      diversity) and slight sample-to-sample dissimilarities in bacterial community
      structures (beta diversity) were noted among different MSC groups. Further,
      predicting the functional capabilities of microbial communities by reconstruction
      of unobserved states showed that many pathways related to cell motility were
      differentially enriched among the three MSC groups. CONCLUSION: Collectively,
      these results indicate a potential association of oral microbiome with the
      mutational changes in OSCC.

PMID- 29362115
TI  - Reader performance in the ultrasonographic evaluation of oropharyngeal carcinoma.
AB  - OBJECTIVE: To examine reader performance in evaluating oropharyngeal anatomy on
      ultrasonography. MATERIALS AND METHODS: Ultrasound images of the oropharynx
      comprising normal and malignant anatomic variants were organized into slideshows.
      Slideshows were administered to 6 readers blinded to participant tumor status and
      with varying experience reading oropharyngeal sonograms. A training slideshow
      oriented readers to images of the oropharynx with and without malignant lesions.
      Readers then evaluated images in a test slideshow for tumor presence and marked
      orthogonal long and short dimensions of the tumor. Results were analyzed for
      accuracy, sensitivity, specificity, inter-reader agreement, and measurement error
      relative to prospectively-identified reference measurements. RESULTS: Eighty
      seven percent of base of tongue (BOT) sonograms were identified correctly by a
      majority of readers. In identifying BOT tumors, median accuracy, sensitivity,
      specificity, and Fleiss's kappa were 79%, 73%, 85%, and 0.51, respectively.
      Median measurement error in the long and short axes for BOT tumors was -2.6%
      (range: -40% to 29%) and -2.6% (range: -56% to 156%), respectively. Eighty-four
      percent of palatine tonsil sonograms were identified correctly by a majority of
      readers. In identifying tonsil tumors, median accuracy, sensitivity, specificity,
      and Fleiss's kappa were 77%, 74%, 78%, and 0.41, respectively. Median measurement
      error in the long and short axes for tonsil tumors was 3.8% (range: -45% to 32%)
      and -6.5% (range: -83% to 42%), respectively. CONCLUSIONS: Overall, US has
      clinically useful sensitivity for identification of oropharyngeal carcinoma among
      readers of diverse clinical backgrounds and experience. US may be useful for the
      evaluation of features such as tumor dimensions.

PMID- 29362116
TI  - Mandibular reconstruction.
AB  - Mandibular reconstruction presents unique functional and aesthetic challenges to
      the reconstructive surgeon. This review will cover current techniques for
      mandibular reconstruction, including the various plating strategies for rigid
      fixation, the choice of osseous donor site, and the concurrent reconstruction of
      associated soft tissue defects. Recent developments and future horizons in
      mandibular reconstruction including the use of virtual surgical planning and
      tissue engineering will also be addressed.

PMID- 29362117
TI  - Reconnoitre ameloblastic carcinoma: A prognostic update.
AB  - AIM: Malignant odontogenic tumor, ameloblastic carcinoma (AC) is challenging to
      study owing to its rarity, complexity and limited availability of literature.
      This further makes it difficult to establish its clinical characteristics and
      prognosis. Our study aimed to evaluate AC's clinico-demographic factors and their
      relation with prognosis and survival. MATERIALS AND METHODS: Literature was
      systematically reviewed for cases pertaining to AC, starting from January 2000 to
      December 2016. All the required data was obtained, arranged and analysed using
      Cox regression ratio and Kaplan Meir survival analysis. From the database, 153
      cases were retrieved as per the inclusion/exclusion criteria. RESULTS: The
      results demonstrated that age of patient, mode of treatment and metastasis
      affects overall survival. The categorisation of AC as primary or secondary type
      does not have any role in determining prognosis. CONCLUSION: Overall survival of
      AC patient depends upon age, site, treatment and metastasis. For a better
      prognosis early surgical management of the tumor appears to be the most
      favourable mode of treatment.

PMID- 29362118
TI  - Late radiation-associated dysphagia in head and neck cancer patients: evidence,
      research and management.
AB  - In head and neck cancer (HNC) scenario, newer radiotherapy (RT) techniques, such
      as intensity modulated RT (IMRT), aim to reduce acute and late toxicity without
      impair tumor response and loco-regional control rates. However, late radiation
      associated dysphagia (RAD) remains a major clinical problem and has gained a
      growing importance in the last few years, especially due to human papilloma virus
      (HPV)-related HNC favorable prognosis. The aim of this review was to provide
      clinical information about late RAD. The main anatomical structures involved in
      swallowing were described, in order to define potential organ at risk and
      available radiation-dose constraints in IMRT plan. Finally, possible
      rehabilitation strategies were proposed. This is expected to represent an
      opportunity for improved multidisciplinary management in HNC patients.

PMID- 29362119
TI  - Viable tumor in salvage neck dissections in head and neck cancer: Relation with
      initial treatment, change of lymph node size and human papillomavirus.
AB  - OBJECTIVES: To identify predictive factors for the presence of viable tumor and
      outcome in head and neck cancer patients who undergo therapeutic salvage neck
      dissections. MATERIALS AND METHODS: Retrospective analysis of 76 salvage neck
      dissections after radiotherapy alone (n = 22), radiotherapy in combination with
      carboplatin/5-fluorouracil (n = 42) or with cetuximab (n = 12). RESULTS: Viable
      tumor was detected in 41% of all neck dissections. Univariate analysis revealed
      initial treatment with radiotherapy without systemic therapy (OR 6.93, 95%CI:
      2.28-21.07, p < .001), increased lymph node size after initial treatment compared
      to pretreatment CT scan (OR 20.48, 95%CI: 2.46-170.73, p = .005), more extensive
      neck dissections (OR 8.40, 95%CI: 2.94-23.98, p < .001), and human papillomavirus
      negative cancer (OR 4.22, 95%CI: 1.10-16.22, p = .036) as predictors of viable
      tumor. Patients with decreased or stable, but persistently enlarged lymph node
      size after chemoradiation had a significantly lower chance of viable tumor (OR
      0.15, 95%CI: 0.05-0.41, p < .001). Disease-specific 5-year survival was 34% in
      case of viable tumor, and 78% when no viable tumor was found (p < .001).
      CONCLUSIONS: Viable tumor in salvage neck dissections is associated with reduced
      survival. Radiotherapy alone, human papillomavirus negative cancer and increase
      in lymph node size, are associated with viable tumor in salvage neck dissections.
      In case of decreased or stable lymph node size after chemoradiation, watchful
      waiting could be considered.

PMID- 29362120
TI  - RETRACTED: Straticyte demonstrates prognostic value over oral epithelial
      dysplasia grade for oral potentially malignant lesion assessment.

PMID- 29362121
TI  - Treatment outcomes of nasopharyngeal carcinoma in modern era after intensity
      modulated radiotherapy (IMRT) in Hong Kong: A report of 3328 patients (HKNPCSG
      1301 study).
AB  - PURPOSE: To evaluate treatment outcomes, failure patterns and late toxicities in
      patients with nasopharyngeal carcinoma (NPC) treated by intensity modulated
      radiotherapy (IMRT) in 6 public hospitals in Hong Kong over a 10-year period from
      2001 to 2010. MATERIAL AND METHODS: Eligible patients were identified through the
      Hong Kong Cancer Registry data base. Clinical information was retrieved and
      verified by oncologists working in the individual centers. Treatment details,
      survival outcomes and late toxicities were analyzed. RESULTS: A total of 3328
      patients were recruited. The median follow-up time was 80.2 months. The 8-year
      actuarial overall survival (OS), local failure-free survival (LFFS), regional
      failure-free survival (RFFS), distant failure free survival (DFFS), progression
      free survival (PFS) for the whole group was 68.5%, 85.8%, 91.5%, 81.5% and 62.6%
      respectively. Male gender, older age, advanced T and N stage were adverse
      prognostic factors for OS, DFFS and PFS, whereas use of chemotherapy in form of
      concurrent chemo-irradiation (CRT), neoadjuvant + CRT, or CRT + adjuvant
      chemotherapy were favorable prognostic factors for OS and PFS. The local control
      was adversely affected by advanced T stage. N stage remained as the single
      adverse prognostic factor for regional control. Distant metastasis was the
      commonest site of failure. CONCLUSION: IMRT is an effective treatment for NPC
      with excellent overall loco-regional control. Distant metastasis is the major
      site of failure. Concurrent chemotherapy with cisplatin has an established role
      in NPC patients treated by IMRT.

PMID- 29362122
TI  - Venous thromboembolism incidence in head and neck surgery patients: Analysis of
      the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database.
AB  - OBJECTIVE: Venous thromboembolism (VTE) may cause significant postoperative
      morbidity and mortality; research in other surgical fields suggests an elevated
      VTE risk persists up to 30 days after surgery, beyond hospital discharge. We
      performed a review of the Veteran's Affairs Surgical Quality Improvement Project
      (VASQIP) database to determine the 30-day incidence of VTE following head and
      neck surgery and assess the proportion of VTE that occur post-discharge.
      MATERIALS AND METHODS: A retrospective review was performed of all head and neck
      ablative procedures captured in the VASQIP database between 1991 and 2015. Post
      operative VTE incidence was determined and the relationship of pre-operative data
      and post-operative mortality to VTE incidence was assessed. RESULTS: 48,986
      patients were included in the study; there were 152 VTE events (0.31%) and 39
      (25.7%) occurred post-discharge. Lower VTE rates were found in parotidectomies
      (0.22%) and thyroid/parathyroid cases (0.23%), and higher rates in free flap
      (1.52%) and laryngectomy cases (0.69%). Age >70, recent weight loss, low serum
      albumin, and increased surgical time were all associated with increased VTE
      incidence on multivariate analysis. 90-day mortality in patients without VTE was
      2.1% compared to 19.7% in patients who experienced a VTE. CONCLUSION: While the
      documented rate of VTE in a national dataset is relatively low following head and
      neck surgeries, it is elevated with certain procedure categories and following
      long operations, and a significant proportion of VTE occur post-discharge. This
      study provides baseline data to better inform efforts to risk-stratify and
      customize thromboprophylaxis for patients undergoing head and neck procedures.

PMID- 29362123
TI  - Intraoral ultrasonography to measure tumor thickness of oral cancer: A systematic
      review and meta-analysis.
AB  - Early oral cancer is preferably treated by surgery. Its complete removal is
      essential for locoregional control and disease-free survival. Inadequate
      resection margins require adjuvant therapy such as re-resection or
      (chemo)radiation, that causes extra morbidity and oral discomfort. Intraoral
      ultrasonography (US) is reported to be of value in determining tumor thickness.
      Intraoperative visualization of the tumor may facilitate the resection and ensure
      adequate surgical margins. Furthermore, accurate prediction of tumor thickness
      could help determine the treatment strategy of the clinically node-negative neck,
      as thickness and depth of invasion are predictors of cervical metastasis as well
      as prognosticators of survival. The 8th edition of the American Joint Committee
      on Cancer staging system for oral squamous cell carcinoma has included depth of
      invasion as parameter for cT-stage. The aim of this review is to analyze the
      accuracy of intraoral US in determining tumor thickness in oral cancer. A
      systematic search was conducted, and the quality of the included papers was
      assessed using the QUADAS-2 tool for diagnostic accuracy studies. Subsequently, a
      meta-analysis was performed on the available individual participant data of 240
      patients. Most of the twelve included studies focused on T1-2 tongue cancer (n =
      129). Meta-analysis showed a high correlation in tumor thickness within this
      subgroup as measured by intraoral US and histopathology (r = 0.82, p < .001),
      with minor overestimation of 0.5 mm on US. It is concluded that intraoral US is
      very accurate in determining tumor thickness in early oral tongue cancer.

PMID- 29362124
TI  - Postoperative staging of the neck dissection using extracapsular spread and lymph
      node ratio as prognostic factors in HPV-negative head and neck squamous cell
      carcinoma patients.
AB  - OBJECTIVES: The presence of nodes with extracapsular spread (ECS) and the lymph
      node ratio (LNR) have prognostic competence in the pathologic evaluation of
      patients with a head and neck squamous cell carcinoma (HNSCC) treated with a neck
      dissection. The purpose of this study is to assess the effect of ECS & LNR on
      prognosis of HPV negative HNSCC patients treated with neck dissection and to
      compare to 8th edition TNM/AJCC classification. MATERIALS AND METHODS: We carried
      out a retrospective study of 1383 patients with HNSCC treated with a neck
      dissection between 1985 and 2013. We developed a classification of the patients
      according to the presence of nodes with ECS and the LNR value with a recursive
      partitioning analysis (RPA) model. RESULTS: We obtained a classification tree
      with four terminal nodes: for patients without ECS (including patients pN0) the
      cut-off point for LNR was 1.6%, while for patients with lymph nodes with ECS it
      was 11.4%. The 5-year disease-specific survival for patients without ECS/LNR <
      1.6% was 83.3%; for patients without ECS/LNR >= 1.6% it was 61.5%; for patients
      with ECS/LNR < 11.4% it was 33.7%; and for patients with ECS/LNR >= 11.4% it was
      18.5%. The classification obtained with RPA had better discrimination between
      categories than the 8th edition of the TNM/AJCC classification. CONCLUSION: ECS
      status and LNR value proved high prognostic capacity in the pathological
      evaluation of the neck dissection. The combination of ECS and LNR improved the
      predictive capacity of the 8th edition of the TNM/AJCC classification in HPV
      negative HNSCC patients.

PMID- 29362125
TI  - Head and neck squamous cell carcinoma of unknown primary: Outcomes of a pre
      defined institutional treatment policy in a region with a high prevalence of skin
      cancer.
AB  - OBJECTIVES: To determine the rate of subsequent primary site failure in patients
      with head and neck squamous cell carcinoma of unknown primary (UKP HNSCC) in a
      region with a high prevalence of cutaneous squamous cell carcinoma, according to
      a pre-determined institutional policy. Secondary aims included regional and
      distant control, and overall survival. MATERIAL AND METHODS: Patients presenting
      between April 2005 and June 2016 to the Princess Alexandra Hospital Head and Neck
      Multidisciplinary Meeting with UKP HNSCC from either presumed mucosal or
      cutaneous sites treated with curative intent were eligible. Patients with
      presumed mucosal origin were treated with radiation therapy (RT) with or without
      chemotherapy, while patients with presumed cutaneous SCC were treated with
      surgery and post-operative RT with or without chemotherapy. RESULTS: A total of
      63 patients met the inclusion criteria. Median follow up duration was 3.9 years
      (IQR 2.07-5.14). There were no subsequent primary site failures. The rate of
      nodal failure among presumed mucosal patients was 11.5%, and 8.1% among presumed
      cutaneous patients. The rate of distant metastatic failure was 11.1% among all
      patients. The estimated 5 year overall survival was 71.2% (95% CI 59.2-85.7%).
      CONCLUSION: Treatment according to our pre-defined institutional policy for UKP
      HNSCC in a region with a high prevalence of cutaneous SCC appears to be safe and
      effective with low rates of mucosal primary emergence and nodal failure.

PMID- 29362126
TI  - A squamous odontogenic tumor following an orthodontic micro-screw: A rare case
      report and review of the literature.
AB  - We reported a very rare case of squamous odontogenic tumor(SOT) in a 23-year-old
      female. The tumor arose after an implanting operation of an orthodontic micro
      screw, and was definitely diagnosed by the histopathological examination. Based
      on the case report and a review of the literature, we discussed about the general
      features, differential diagnosis and pathogenesis of SOT.

PMID- 29362127
TI  - Sensitivity and specificity of oral HPV detection for HPV-positive head and neck
      cancer.
AB  - BACKGROUND: The incidence of HPV-related head and neck squamous cell carcinoma
      (HPV-HNSCC) is increasing. Oral samples are easy and non-invasive to collect, but
      the diagnostic accuracy of oral HPV detection methods for classifying HPV
      positive HNSCC tumors has not been well explored. METHODS: In a systematic
      review, we identified eight studies of HNSCC patients meeting our eligibility
      criteria of having: (1) HPV detection in oral rinse or oral swab samples, (2)
      tumor HPV or p16 testing, (3) a publication date within the last 10 years
      (January 2007-May 2017, as laboratory methods change), and (4) at least 15 HNSCC
      cases. Data were abstracted from each study and a meta-analysis performed to
      calculate sensitivity and specificity. RESULTS: Eight articles meeting inclusion
      criteria were identified. Among people diagnosed with HNSCC, oral HPV detection
      has good specificity (92%, 95% CI = 82-97%) and moderate sensitivity (72%, 95% CI
      = 45-89%) for HPV-positive HNSCC tumor. Results were similar when restricted to
      studies with only oropharyngeal cancer cases, with oral rinse samples, or testing
      for HPV16 DNA (instead of any oncogenic HPV) in the oral samples. DISCUSSION:
      Among those who already have HNSCC, oral HPV detection has few false-positives
      but may miss one-half to one-quarter of HPV-related cases (false-negatives).
      Given these findings in cancer patients, the utility of oral rinses and swabs as
      screening tests for HPV-HNSCC among healthy populations is probably limited.

PMID- 29362128
TI  - Assessing miRNAs profile expression as a risk stratification biomarker in oral
      potentially malignant disorders: A systematic review.
AB  - OBJECTIVES: This paper aims to systematically review current findings on altered
      expression of miRNAs in OPMDs and whether they can be used as risk stratification
      biomarkers. METHODS: Studies were collated after searching three different
      electronic databases: PubMed, Embase, Medline. Additional searches were carried
      out through cross checking the bibliographies of selected articles. After a
      thorough selection process made by two of the authors, 40 articles met the
      inclusion criteria and were included in the review. Studies were assessed and
      analysed in terms of how the candidate miRNA biomarkers were differentially
      expressed and validated. RESULTS: The included studies examined the expression of
      miRNAs from human specimens (blood serum/plasma, saliva, tissue) as diagnostic or
      prognostic biomarkers in patients with OPMDs, some of which have been utilised as
      risk stratification biomarkers for malignant transformation and have showed
      promising findings. CONCLUSION: The current evidence to support or refute the
      prognostic utility of miRNAs in predicting cancer progression in OPMDs is
      equivocal. Further longitudinal prospective studies with solid study design are
      warranted.

PMID- 29362130
TI  - Influence of tumor and microenvironment characteristics on diffusion-weighted
      imaging in oropharyngeal carcinoma: A pilot study.
AB  - OBJECTIVES: Diffusion weighted imaging (DWI) is a frequently performed MRI
      sequence in cancer patients. While previous studies have shown the clinical value
      of the apparent diffusion coefficient (ADC) for response prediction and response
      monitoring, less is known about the biological background of ADC. In the tumor
      microenvironment, hypoxia and increased proliferation of tumor cells contribute
      to resistance to (radio-)therapy, while high T-cell influx is related to better
      prognosis. We investigated the correlation between these three tissue
      characteristics and ADC in 20 oropharyngeal squamous cell carcinoma patients.
      MATERIALS AND METHODS: 20 patients with oropharyngeal squamous cell carcinoma
      (OPSCC) who underwent 1.5 T MRI, including DWI were included in this pilot study.
      Corresponding formalin-fixed paraffin-embedded tumor tissues were
      immunohistochemically analyzed for protein expression of hypoxia-inducible factor
      1a (HIF-1a), Ki-67 and CD3. Expression of these markers was correlated with ADC.
      RESULTS: ADC negatively correlated with Ki-67 expression (p = .024) in tumor
      cells. There was a significant negative correlation between ADC and CD3-positive
      cell count (p = .009). No correlation was observed between HIF-1a expression and
      ADC. CONCLUSION: This study suggests that ADC reflects characteristics of tumor
      cells as well as the surrounding microenvironment. Interestingly, high tumor
      proliferation (a negative prognostic factor) and high T-cell influx (a beneficial
      prognostic factor) are both associated with a lower ADC. Further studies should
      be performed to correlate ADC to these histological characteristics in relation
      to previously known factors that affect ADC, to gain further knowledge on the
      role of DW-MRI in diagnostics and personalized medicine.

PMID- 29362129
TI  - Proportion of CD4 and CD8 tumor infiltrating lymphocytes predicts survival in
      persistent/recurrent laryngeal squamous cell carcinoma.
AB  - Tumor infiltrating lymphocytes (TILs) have been shown to be an important
      prognostic factor in patients with previously untreated head and neck cancer.
      After organ preservation therapy for laryngeal cancer and subsequent
      persistence/recurrence, the prognostic value of TILs is unknown. Our goal was to
      determine if TILs have value as a prognostic biomarker in patients with
      surgically salvageable persistent/recurrent laryngeal squamous cell carcinoma.
      Levels of TILs were quantified on tissue microarrays from 183 patients undergoing
      salvage total laryngectomy for persistent/recurrent laryngeal cancer after
      radiation or chemoradiation between 1997 and 2014. Demographic and clinical data
      were abstracted. Immunohistology evaluation included CD4, CD8, PDL-1, p16, CD31,
      Vimentin, EGFR, and p53. Elevated levels of either CD8 or CD4 positive TILs were
      associated with improved disease specific survival (CD8: HR 0.46, 95% CI 0.24
      0.88, CD4: HR 0.43; 95% CI 0.21-0.89) and disease free survival (CD8: HR 0.53,
      95% CI 0.29-0.94, CD4: HR 0.52; 95% CI 0.27-0.99). Levels of CD8 (HR 0.74; 95% CI
      0.47-1.17) or CD4 (HR 0.66; 95% CI 0.40-1.08) TILs were not significantly
      associated with overall survival. In bivariate analysis, patients with elevated
      CD4 and/or CD8 TILs had significantly improved disease specific survival (HR
      0.42; 95% CI 0.21-0.83) and disease free survival (HR 0.45; 95% CI 0.24-0.84)
      compared to patients with low levels of CD4 and CD8. PDL-1, p16, CD31, Vimentin,
      EGFR, and p53 were not significant prognostic factors. On multivariate analysis,
      elevated CD8 TILs were associated with improved disease specific survival (HR
      0.35; 95% CI 0.14-0.88, p = .02) and disease free survival (HR 0.41; 95% CI 0.17
      0.96, p = .04). CD8, and possibly CD4, positive TILs are associated with
      favorable disease free and disease specific survival for recurrent/persistent
      laryngeal cancer.

PMID- 29362131
TI  - 59 years old male with local advanced adenoid cystic carcinoma of the hypopharynx
      - A case report and a review of the literature.
AB  - Minor Salivary Gland tumours are rare, representing 2% of the head and neck
      tumours and less than 1% of hypopharyngeal cancers. The most common subtype of
      minor salivary gland tumours is adenoid cystic carcinoma. Although there are
      several case reports discussed it, there are only two reports discussing
      hypopharyngeal presentation in the literature, and they were treated by surgical
      resection. Despite that, our case report still to be unique as it presents a case
      of irresectable locally advanced tumour subjected to a trial of induction
      therapy.

PMID- 29362132
TI  - HLA class I antigen processing machinery (APM) component expression and PD-1:PD
      L1 pathway activation in HIV-infected head and neck cancers.
AB  - Human immunodeficiency virus (HIV)-infected individuals are at increased risk for
      developing several non-AIDS related malignancies and are often excluded from
      cancer immunotherapy regimens. To evaluate the immune competence of this cancer
      patient population, we evaluated HLA class I antigen presenting machinery (APM)
      component expression and PD-1:PD-L1 pathway upregulation in HIV(+) and HIV(-)
      head and neck cancers (HNCs). Sixty-two HIV(+) and 44 matched HIV(-) controls
      diagnosed with HNC between 1991 and 2011 from five tertiary care referral centers
      in the United States were identified. HLA class I APM component, PD-1, and PD-L1
      expression were analyzed by immunohistochemical staining with monoclonal
      antibodies (mAbs). Clinical data was abstracted from the medical records. There
      was no significant difference between the cases and controls in LMP2, TAP1, HLA-A
      and HLA-B/C, as well as PD-1 and PD-L1 expression. Overall, 62% of all subjects
      had high PD-1 expression and 82% of the subjects expressed PD-L1 within the tumor
      microenvironment. LMP2, HLA-A and HLA-B/C expression were significantly
      associated with moderate to high PD-1 expression in the HIV(+) HNC cases (p =
      .004, p = .026, and p = .006, respectively) but not in the HIV(-) controls. In
      addition, HLA-A expression was significantly associated with PD-L1 expression in
      the HIV(+) HNC cases only (p = .029). HIV-infected individuals diagnosed with HNC
      do not have any detectable defects in HLA class I APM component expression and in
      PD-1:PD-L1 pathway activation. Given the current successes of HAART therapy in
      maintaining immune cell counts, HIV(+) patients diagnosed with cancer may benefit
      from the recently FDA-approved immune checkpoint blockade therapy.

PMID- 29362133
TI  - Prediction of distant metastasis and survival in adenoid cystic carcinoma using
      quantitative 18F-FDG PET/CT measurements.
AB  - OBJECTIVES: Adenoid cystic carcinoma (AdCC) in the salivary gland shows a high
      rate of distant metastasis, which is related to the resulting poor prognosis. We
      therefore examined the role of pretreatment 18F-FDG PET/CT for prediction of
      distant metastasis, recurrence/progression, and survival in AdCC. METHODS: This
      study included 52 patients who underwent pretreatment 18F-FDG PET/CT scanning and
      subsequent treatments for AdCC. Maximum, mean, and peak standardized uptake value
      (SUVmax, SUVmean, and SUVpeak), metabolic tumor volume (MTV), and total lesion
      glycolysis (TLG) were measured on 18F-FDG PET/CT. Univariate and multivariate Cox
      proportional hazards regression analyses were used to identify associations
      between the quantitative measurements of 18F-FDG PET, and progression-free
      survival (PFS), distant metastasis-free survival (DMFS), and disease-specific
      survival (DSS). RESULTS: Distant metastases were found in 20 (39%) patients: 6
      (12%) at initial diagnosis and 14 (27%) during the median follow-up of 72 months
      after treatment. Univariate analyses showed that all the 18F-FDG PET parameters
      of SUVmax, SUVmean, SUVpeak, MTV, and TLG were significantly associated with
      overall PFS, DMFS, and OS (all P < .05). After controlling for
      clinicopathological variables, SUVmax remained an independent factor predictive
      of PFS (P = .001), while MTV and TLG were independent predictors of DMFS (P =
      .009) and DSS (P = .017). Patients with MTV > 14.8 mL showed a 5.9-fold higher
      risk of distant metastasis and a 4.2-fold higher risk of disease-specific death
      than those with a lower MTV. CONCLUSIONS: Quantitative measurements using 18F-FDG
      PET/CT are useful for predicting tumor progression, distant metastasis, and
      survival in patients with AdCC.

PMID- 29362134
TI  - First case of Furuncular Myiasis due to Cordylobia anthropophaga in a Latin
      American resident returning from Central African Republic.
AB  - Myiasis is a temporary infection of the skin or other organs with fly larvae.1
      The larvae develop into boil-like lesions. Creeping sensations and pain are
      usually described by patients. Following the maturation of the larvae,
      spontaneous exiting and healing is experienced. Herein we present a case of a
      traveler returning from Central African Republic. She does not recall insect
      bites. She never took off her clothing for recreational bathing, nor did she
      visit any rural areas. The lesions appeared on unexposed skin. The specific
      diagnosis was performed by morphologic characterization of the larvae, resulting
      in Cordylobia anthropophaga, the dominant form of myiasis in Africa. To our
      knowledge, this is the first reported case of C. anthropophaga in Latin America.

PMID- 29362135
TI  - TSG-6: A multifunctional protein with anti-inflammatory and tissue-protective
      properties.
AB  - Tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) is an inflammation
      associated secreted protein that has been implicated as having important and
      diverse tissue protective and anti-inflammatory properties, e.g. mediating many
      of the immunomodulatory and beneficial activities of mesenchymal stem/stromal
      cells. TSG-6 is constitutively expressed in some tissues, which are either highly
      metabolically active or subject to challenges from the environment, perhaps
      providing protection in these contexts. The diversity of its functions are
      dependent on the binding of TSG-6 to numerous ligands, including matrix molecules
      such as glycosaminoglycans, as well as immune regulators and growth factors that
      themselves interact with these linear polysaccharides. It is becoming apparent
      that TSG-6 can directly affect matrix structure and modulate the way
      extracellular signalling molecules interact with matrix. In this review, we focus
      mainly on the literature for TSG-6 over the last 10 years, summarizing its
      expression, structure, ligand-binding properties, biological functions and
      highlighting TSG-6's potential as a therapeutic for a broad range of disease
      indications.

PMID- 29362137
TI  - Erratum to "Hydroxyapatite and calcium pyrophosphate crystals mimicking gout in
      systemic sclerosis" [Reumatol Clin. 2017;13(4):235-236].

PMID- 29362138
TI  - Texture analysis and machine learning to characterize suspected thyroid nodules
      and differentiated thyroid cancer: Where do we stand?
AB  - In thyroid imaging, "texture" refers to the echographic appearence of the
      parenchyma or a nodule. However, definition of the image characteristics is
      operator dependent and influenced by the operator's experience. In a more
      objective texture analysis, a variety of mathematical methods are used to
      describe image inhomogeneity, allowing assessment of an image by means of
      quantitative parameters. Moreover, this approach may be used to develop an
      efficient computer-aided diagnosis (CAD) system to yield a second opinion when
      differentiating malignant and benign thyroid lesions. The aim of this review is
      to summarize the available literature data on texture analysis, with and without
      CAD, in patients with suspected thyroid nodules or differentiated thyroid cancer,
      and to assess the current state of the approach.

PMID- 29362136
TI  - The diamond anniversary of tissue transglutaminase: a protein of many talents.
AB  - Tissue transglutaminase (tTG) is capable of binding and hydrolyzing GTP, as well
      as catalyzing an enzymatic transamidation reaction that crosslinks primary amines
      to glutamine residues. tTG adopts two vastly different conformations, depending
      on whether it is functioning as a GTP-binding protein or a crosslinking enzyme.
      It has been shown to have important roles in several different aspects of cancer
      progression, making it an attractive target for therapeutic intervention. Here,
      we highlight many of the major findings involving tTG since its discovery 60
      years ago, and describe recent drug discovery efforts that target specific
      activities or conformations of this unique protein.

PMID- 29362139
TI  - Cystic renal masses: An imaging update.
AB  - Management of incidental renal masses is in evolution. Recognition that cystic
      renal tumors generally act in an indolent fashion has led to less aggressive
      intervention. The ability of radiologists to stratify risk of malignancy, and in
      some cases, specify a precise diagnosis, is paramount to patient management. We
      review pathologies that present as cystic renal masses and how to best stratify
      malignancy risk.

PMID- 29362140
TI  - Evaluation of virtual monoenergetic imaging algorithms for dual-energy carotid
      and intracerebral CT angiography: Effects on image quality, artefacts and
      diagnostic performance for the detection of stenosis.
AB  - PURPOSE: To investigate the impact of traditional (VMI) and noise-optimized
      virtual monoenergetic imaging (VMI+) algorithms on quantitative and qualitative
      image quality, and the assessment of stenosis in carotid and intracranial dual
      energy CTA (DE-CTA). MATERIALS AND METHODS: DE-CTA studies of 40 patients
      performed on a third-generation 192-slice dual-source CT scanner were included in
      this retrospective study. 120-kVp image-equivalent linearly-blended, VMI and VMI+
      series were reconstructed. Quantitative analysis included evaluation of contrast
      to-noise ratios (CNR) of the aorta, common carotid artery, internal carotid
      artery, middle cerebral artery, and basilar artery. VMI and VMI+ with highest
      CNR, and linearly-blended series were rated qualitatively. Three radiologists
      assessed artefacts and suitability for evaluation at shoulder height, carotid
      bifurcation, siphon, and intracranial using 5-point Likert scales. Detection and
      grading of stenosis were performed at carotid bifurcation and siphon. RESULTS:
      Highest CNR values were observed for 40-keV VMI+ compared to 65-keV VMI and
      linearly-blended images (P < 0.001). Artefacts were low in all qualitatively
      assessed series with excellent suitability for supraaortic artery evaluation at
      shoulder and bifurcation height. Suitability was significantly higher in VMI+ and
      VMI compared to linearly-blended images for intracranial and ICA assessment (P <
      0.002). VMI and VMI+ showed excellent accordance for detection and grading of
      stenosis at carotid bifurcation and siphon with no differences in diagnostic
      performance. CONCLUSION: 40-keV VMI+ showed improved quantitative image quality
      compared to 65-keV VMI and linearly-blended series in supraaortic DE-CTA. VMI and
      VMI+ provided increased suitability for carotid and intracranial artery
      evaluation with excellent assessment of stenosis, but did not translate into
      increased diagnostic performance.

PMID- 29362141
TI  - Renal cortical volume: High correlation with pre- and post-operative renal
      function in living kidney donors.
AB  - BACKGROUND: CT volumetry has previously been proposed as an alternative to
      scintigraphy for the evaluation of pre-donation split renal function and the
      prediction of post-donation renal function in living kidney donors. The aim of
      our study was to retrospectively assess the relevance of three CT volumetry
      techniques for estimating pre-donation kidney function and predicting the risk
      for chronic kidney disease (CKD) at 1-year post-nephrectomy in a French cohort of
      living donors using isotopic measures of kidney function. METHODS: Kidney volume
      was quantified pre-donation for 105 donors using three methods total parenchymal
      three-dimensional renal volume (3DRV), total parenchymal renal volume contouring
      (RVCt), and renal cortical volume (RCoV). Subjects also had a 51Cr-EDTA
      scintigraphy to measure glomerular filtration rate (mGFR) pre-donation and 1-year
      after donation. For each volume, we tested for association with mGFR using
      univariate regression models, and computed receiver operating characteristics
      analyses to assess their predictive potential of post-donation CKD. RESULTS: Our
      population was composed of healthy subjects, who were predominantly female (69%)
      with a median age at donation of 51yo. Median mGFR was 102 mL/min/1.73 m2 at pre
      donation and 66 mL/min/1.73 m2 1-year after nephrectomy. The pre-donation median
      volume of the preserved kidney was 156 cm3, 163 cm3 and 99 cm3 for the 3DRV, RVCt
      and RCoV methods respectively, with a high correlation observed between each
      technique (R > 0.84). For all methods, total kidney volume was significantly
      associated with pre-donation mGFR (P < 0.001). Preserved kidney volume was also
      strongly correlated with post-donation mGFR (P < 0.0001), with the strongest
      correlation observed for RCoV (R = 0.60 vs. R = 0.39 and R = 0.51 for 3DRV and
      RVCt, respectively). Finally, the RCoV method yielded the best predictive value
      of 1-year post-donation CKD (AUC = 0.80 vs. AUC = 0.76 and 0.70 for RVCt and
      3DRV, respectively). CONCLUSIONS: In our cohort of healthy donors with measured
      kidney function, cortical volumetry (RCoV) appears as the best volumetric
      technique to use as a surrogate to scintigraphy for estimating pre-donation split
      renal function and predicting post-donation renal outcomes.

PMID- 29362142
TI  - Diagnostic accuracy of dual-energy computed tomography in bone marrow edema with
      vertebral compression fractures: A meta-analysis.
AB  - PURPOSE: This meta-analysis aimed to evaluate the diagnostic performance of dual
      energy computed tomography (DECT) for the bone marrow edema (BME) in patients
      with vertebral compression fractures. METHODS: The PubMed, EMBASE, and the
      Cochrane Library database were searched up to July 2017 for relevant original
      studies. Data were extracted to calculate the pooled sensitivity, specificity,
      diagnostic odds ratio (DOR), positive and negative likelihood ratios (PLR and
      NLR), and areas under summary receiver operating characteristic (SROC) curves for
      analysis. RESULTS: A total of seven studies including 510 vertebras were
      available for the meta-analysis. Overall pooled sensitivity and specificity of
      DECT for detecting BME were 0.82 (95%CI: 0.76-0.86) and 0.98 (95%CI: 0.97-0.99),
      respectively. The PLR was 29.74 (95%CI: 15.62-56.61), the NLR was 0.19 (95%CI:
      0.11-0.33), and DOR was 201.96 (95%CI: 99.98-407.93). The SROC value was 0.978.
      In addition, a subgroup analysis was conducted according to the mean time
      interval between the DECT and MRI. In 5 studies with more than 2 days interval,
      the pooled sensitivity and specificity of DECT were 0.89 (95%CI: 0.84-0.93) and
      0.98 (95%CI: 0.95-0.99), respectively. The AUC value was 0.979. CONCLUSIONS:
      Current evidence of our meta-analysis indicates that DECT has a high diagnostic
      accuracy in BME of vertebral compression fractures. In addition, DECT may have a
      less sensitive in BME of hyper-acute period.

PMID- 29362143
TI  - Cholangiocarcinoma versus small liver abscess in dual source dual-energy CT
      quantitative parameters.

PMID- 29362144
TI  - Gas-induced susceptibility artefacts on diffusion-weighted MRI of the rectum at
      1.5 T - Effect of applying a micro-enema to improve image quality.
AB  - PURPOSE: Assess whether application of a micro-enema can reduce gas-induced
      susceptibility artefacts in Single-shot Echo Planar Imaging (EPI) Diffusion
      weighted imaging of the rectum at 1.5 T. MATERIALS AND METHODS: Retrospective
      analysis of n = 50 rectal cancer patients who each underwent multiple DWI-MRIs
      (1.5 T) from 2012 to 2016 as part of routine follow-up during a watch-and-wait
      approach after chemoradiotherapy. From March 2014 DWI-MRIs were routinely
      acquired after application of a preparatory micro-enema (Microlax(r); 5 ml; self
      administered shortly before acquisition); before March 2014 no bowel preparation
      was given. In total, 335 scans were scored by an experienced reader for the
      presence/severity of gas-artefacts (on b1000 DWI), ranging from 0 (no artefact)
      to 5 (severe artefact). A score >=3 (moderate-severe) was considered a clinically
      relevant artefact. A random sample of 100 scans was re-assessed by a second
      independent reader to study inter-observer effects. Scores were compared between
      the scans performed without and with a preparatory micro-enema using univariable
      and multivariable logistic regression taking into account potential confounding
      factors (age/gender, acquisition parameters, MRI-hardware, rectoscopy prior to
      MRI). RESULTS: Clinically relevant gas-artefacts were seen in 24.3% (no micro
      enema) vs. 3.7% (micro-enema), odds ratios were 0.118 in univariable and 0.230 in
      multivariable regression (P = 0.0005 and 0.0291). Mean severity score (+/-SD) was
      1.19 +/- 1.71 (no-enema) vs 0.32 +/- 0.77 (micro-enema), odds ratios were 0.321
      (P < 0.0001) and 0.489 (P = 0.0461) in uni- and multivariable regression,
      respectively. Inter-observer agreement was excellent (kappa0.85). CONCLUSION: Use
      of a preparatory micro-enema shortly before rectal EPI-DWI examinations performed
      at 1.5 T MRI significantly reduces both the incidence and severity of gas-induced
      artefacts, compared to examinations performed without bowel preparation.

PMID- 29362145
TI  - Evaluation of an automated breast volume scanner according to the fifth edition
      of BI-RADS for breast ultrasound compared with hand-held ultrasound.
AB  - OBJECTIVES: To investigate the automated breast volume scanner (ABVS) in
      comparison with hand-held ultrasound (HHUS) according to the fifth edition of BI
      RADS ultrasound. MATERIAL AND METHODS: A total of 831 lesions in 786 patients who
      underwent both HHUS and ABVS were included. Three radiologists independently
      evaluated the sonographic features of each lesion according to the fifth BI-RADS
      edition. The kappa coefficient (kappa) was calculated for each BI-RADS descriptor
      and final assessment category. The accuracy of malignancy prediction and
      diagnostic performance of the BI-RADS descriptors were assessed using
      multivariate logistic regression and area under the receiver operator
      characteristic curve (AUC), respectively. RESULTS: ABVS and HHUS showed moderate
      to good interobserver agreement (kappa = 0.53-0.67 and 0.55-0.70, respectively)
      except in associated features (kappa = 0.31 and 0.36, respectively) for BI-RADS
      lexicons. Irregular shape, a non-circumscribed margin, and posterior features
      (combined or shadowing) were independently associated with malignancy in both
      ABVS and HHUS. Calcification presence on ABVS (odds ratio [OR], 95% confidence
      interval [CI]: 2.09, 1.11-3.94) and non-parallel orientation on HHUS (OR, 95% CI:
      2.04, 1.10-3.78) were independently associated with malignancy. There were no
      significant differences between ABVS and HHUS in sensitivity (84.2% vs. 84.2%),
      specificity (80.5% vs. 83.9%), or AUC (0.88 vs. 0.90). CONCLUSIONS: According to
      the fifth BI-RADS edition, ABVS is not statistically significantly different from
      HHUS with regard to interobserver variability and diagnostic performance.

PMID- 29362147
TI  - Anterior cruciate ligament fixation devices: Expected imaging appearance and
      common complications.
AB  - Anterior cruciate ligament reconstruction is a commonly performed orthopaedic
      procedure which has increased in frequency over the past decade. There are a
      variety of fixation devices used to secure grafts within the femoral and tibial
      tunnels during the reconstruction procedure. An understanding of the expected
      appearance of the varied hardware utilized for reconstruction graft fixation, and
      their potential complications is important in the review of post-operative
      imaging. We describe the most common anterior cruciate ligament reconstruction
      fixation devices and illustrate their more frequently documented abnormalities.

PMID- 29362146
TI  - Protruding anterior medial meniscus-An indirect sign of posterior cruciate
      ligament deficiency.
AB  - BACKGROUND: to examine if PROTruding of the Anterior Medial Meniscus (PROTAMM)
      could be an indirect sign of PCL deficiency by comparing PROTAMM to passive
      posterior tibial sagging (PSS) for chronic PCL rupture on routine MRI. METHODS:
      Patients with PCL reconstruction between 2011 and 2016 were included in a case
      control study. Primarily cases with combined ACL/PCL injury were excluded.
      Secondary exclusion criteria were bony fractures, medial meniscus pathology and
      poor quality MRIs. Three (blinded) observers reviewed the pre-operative MRIs
      according to a pre-defined protocol. RESULTS: After applying the inclusion and
      primary exclusion criteria 16 patients were identified in the PCL rupture group.
      The control group consisted of 15 patients. After reviewing the MRIs, 6 were
      excluded due to secondary exclusion criteria. Mean PPS measured 4.8 mm (+/- 4.4
      mm) in the PCL rupture group and 1.8 mm (+/-2.9 mm) in the control group, p =
      0.05. Mean PROTAMM was 3.6 mm (+/-0.6 mm) in the PCL rupture group and 0.7 mm (+/
      0.9 mm) in the control group, p = 0.004. CONCLUSION: We found a mean PROTAMM of
      3.6 mm in patients with PCL rupture. We suggest that this sign, after knee injury
      in an otherwise normal medial meniscus, is a promising indirect sign of PCL
      deficiency compared to PPS. Implementation of this sign in clinical practice may
      improve the sensitivity of routine non-weight bearing MRI in identifying PCL
      deficient knees.

PMID- 29362148
TI  - Utilization of virtual mono-energetic images (MonoE) derived from a dual-layer
      spectral detector CT (SDCT) for the assessment of abdominal arteries in venous
      contrast phase scans.
AB  - OBJECTIVES: To investigate the utilization of virtual mono-energetic images
      (MonoE) at low kiloelectron volt (keV) levels derived from a dual-layer spectral
      detector CT (SDCT) for the assessment of abdominal arteries in venous contrast
      phase scans using arterial phase imaging as an internal reference standard.
      MATERIALS AND METHODS: A total of 50 patients who received arterial and venous
      phase imaging of the abdomen on a SDCT system were included in this study.
      Absolute attenuation, noise, signal- and contrast to noise ratios (SNR; CNR) as
      well as arterial diameters in defined landmarks were assessed. In arterial phase,
      conventional reconstructions (CRART) as well as MonoEART at 40keV and in venous
      phase, conventional reconstructions (CRVEN) as well as MonoEVEN at 70 and 40keV
      were investigated and intra-individual comparisons were performed. If an artery
      stenosis (10 patients) was present, the degree of stenosis was assessed according
      to the system of the North American Symptomatic Carotid Endarterectomy Trial
      (NASCET). RESULTS: MonoE 40keV yielded significantly higher attenuation values
      (in arterial as well as in venous phase) compared to CRART (p<0.001) while noise
      levels were substantially low. This resulted in markedly superior SNR and CNR in
      large vessel compared to CRART. Luminal diameters were significantly smaller in
      MonoE 40keV in both contrast phases compared to CRART (p<0.001), whereas no
      significant differences were found between both MonoE reconstructions (p>=0.92).
      The degree of vessel stenosis was significantly higher in MonoE 40keV of both
      contrast phases compared to CRART (p>=0.02). CONCLUSION: MonoE at low keV of
      venous contrast phase scans derived from a novel SDCT are suitable for the
      assessment of arteries in the abdomen and subsequent stenosis assessment.
      However, MonoE at 40keV constantly showed significant smaller luminal diameters
      than the corresponding conventional reconstructions (including the reference
      standard). This is possibly due to an improved differentiation of the vessel
      lumen from the wall and raises the question, which imaging technique should be
      used as an appropriate reference standard for vascular SDCT imaging studies.

PMID- 29362149
TI  - Strain of ascending aorta on cardiac magnetic resonance in 1027 patients:
      Relation with age, gender, and cardiovascular disease.
AB  - OBJECTIVES: To evaluate ascending aortic strain (AAS) with cardiac magnetic
      resonance (CMR) in a large consecutive series of patients with different types of
      cardiovascular disease (CVD). METHODS: Two-dimensional phase-contrast gradient
      echo sequences of the ascending aorta were retrospectively reviewed in 1027
      patients (726 males, 301 females). Aortic lumen area was segmented using a semi
      automatic approach to calculate AAS values. Subgroup analysis was performed for
      patients with normal CMR, tetralogy of Fallot (ToF), and ischemic heart disease
      (IHD). Multivariate and post-hoc analyses were performed to evaluate the effect
      of age, gender, and CVD on AAS values. Shapiro-Wilk, three- and two-way ANOVA,
      Mann-Whitney U, and Spearman correlation statistics were used. RESULTS:
      Multivariate analysis showed significant differences in AAS among decades of age
      (p<0.001), genders (p=0.006) and CVD subgroups (p<0.001) without interaction
      among these factors. A gender-related difference (higher AAS in females) was
      significant in ToF (p=0.008), while an AAS reduction during aging was observed in
      all CVD subgroups. Post-hoc analysis showed a significantly lower AAS in ToF and
      IHD patients compared to subjects with normal CMR (p<0.001). CONCLUSION:
      Differences in age, gender, and CVD independently affect AAS. The lower AAS
      observed in ToF fosters its assessment during follow-up in adulthood. Future
      studies on causes and clinical implications of a higher AAS in females affected
      by ToF are warranted.

PMID- 29362150
TI  - CT and MR imaging for solid renal mass characterization.
AB  - As our understanding has expanded that relatively large fraction of incidentally
      discovered renal masses, especially in small size, are benign or indolent even if
      malignant, there is growing acceptance of more conservative management including
      active surveillance for small renal masses. As for advanced renal cell carcinomas
      (RCCs), nonsurgical and subtype specific treatment options such as immunotherapy
      and targeted therapy is developing. On these backgrounds, renal mass
      characterization including differentiation of benign from malignant tumors, RCC
      subtyping and prediction of RCC aggressiveness is receiving much attention and a
      variety of imaging techniques and analytic methods are being investigated. In
      addition to conventional imaging techniques, integration of texture analysis,
      functional imaging (i.e. diffusion weighted and perfusion imaging) and
      multivariate diagnostic methods including machine learning have provided
      promising results for these purposes in research fields, although standardization
      and external, multi-institutional validations are needed.

PMID- 29362151
TI  - Posterior tibial tendon dysfunction: Clinical and magnetic resonance imaging
      findings having histology as reference standard.
AB  - OBJECTIVE: To investigate the correlation between MRI, clinical tests,
      histopathologic features of posterior tibial tendon (PTT) dysfunction in patients
      with acquired adult flatfoot deformity surgically treated with medializing
      calcaneal osteotomy and flexor digitorum longus tendon transposition. MATERIALS
      AND METHODS: Nineteen patients (11 females; age: 46 +/- 15 year, range 18-75)
      were pre-operatively evaluated using the single heel rise (HR) and the first
      metatarsal rise (FMR) sign tests. Two reviewers graded the PTT tears on a I-III
      scale and measured the hindfoot valgus angle on the pre-operative MRI of the
      ankle. The specimens of the removed portion of PTT were histologically analysed
      by two pathologists using the Bonar and Movin score. Linear regression,
      Spearman's rank-order, and intraclass correlation coefficient (ICC) statistics
      were used. RESULTS: ICC for MRI was excellent (0.952). Correlation between FMR
      and HR tests was at limit of significance (r = 0.454; P = 0.051). The HR and FMR
      tests were significantly correlated to the Movin score (r = 0.581; P = 0.009 and
      r = 0.538; P = 0.018, respectively) and were not significantly correlated to the
      Bonar score (both with a r = 0.424; P = 0.070). PTT tendinopathy grading at MRI
      was significantly correlated to the FMR test (p = 0.041) but not to the hindfoot
      valgus angle (p = 0.496), the HR test (p = 0.943), the Bonar score (p = 0.937),
      and the Movin score (p = 0.436). The hindfoot angle was not correlated to any of
      the other variables (p > 0.264). CONCLUSION: For PTT dysfunction, there is high
      correlation between HR and FMR test and histology evaluated using the Movin
      score, while no correlation was seen for the Bonar score. Semiquantitative
      grading of PTT dysfunction at MRI only correlates to the FMR and not to
      histology. The hindfoot valgus angle is not correlated to any of the considered
      variables.

PMID- 29362152
TI  - Peripheral zone lesions of intermediary risk in multiparametric prostate MRI:
      Frequency and validation of the PI-RADSv2 risk stratification algorithm based on
      focal contrast enhancement.
AB  - PURPOSE: To validate the risk stratification algorithm of the Prostate Imaging
      Reporting and Data System (PI-RADSv2) for intermediary risk lesions (PI-RADSv2
      category 3) in the peripheral zone based on focal contrast enhancement and to
      compare cancer rates in category 3, upgraded category 4 and category 4 based on
      markedly low ADC value. MATERIALS AND METHODS: We retrospectively analyze 172
      consecutive patients undergoing prostate MRI with 315 histopathologically
      verified lesions. We select all lesions either assigned category 3 or category 4
      in the peripheral zone for further analysis. We compare cancer rates with the two
      sided chi-squared test. To determine inter-observer agreement about contrast
      enhancement two blinded radiologists evaluate the subset of category 3 lesions
      based on the diffusion weighted sequence. RESULTS: The frequency of peripheral PI
      RADS 3, upgraded PI-RADS 4 and PI-RADS 4 lesions based on markedly low ADC value
      is 10.8%, 10.8% and 20.3%, respectively. Cancer rates (significant cancer only)
      in these subgroups are 8.8% (3/34), 23.5% (8/34) and 40.6% (26/64), P < 0.01.
      Inter-observer agreement is moderate for evaluation of contrast enhancement with
      kappa values between 0.46 and 0.5. CONCLUSION: We demonstrate a trend of
      increasing cancer rate from PI-RADSv2 category 3 to upgraded category 4 to
      category 4 based on markedly low ADC value. Peripheral lesions of intermediary
      risk in the diffusion weighted sequence account for 21.6% of all prostate lesions
      encountered. Since it is likely that patient management recommendations will be
      linked to assessment categories in future versions of PI-RADS, cancer rates in
      upgraded category 4 and category 4 based on markedly low ADC values should be in
      a similar range. We conclude that in future studies of PI-RADSv2 upgraded
      category 4 and category 4 based on markedly low ADC value should be reported
      separately to generate a database for meta-analysis of cancer rates.

PMID- 29362153
TI  - Endovascular treatment of intracranial vertebrobasilar artery dissecting
      aneurysms: Parent artery occlusion versus flow diverter.
AB  - PURPOSE: To compare the safety and efficacy of endovascular parent artery
      occlusion (PAO) and flow diverter (FD) treatment in treating vertebrobasilar
      dissecting aneurysms (VBDAs). METHODS: A review of a prospective aneurysm
      database at our institution was performed to identify all consecutive patients
      with intracranial VBDAs managed with endovascular treatment, which were either
      PAO or FD. Clinical and imaging findings were compared between the two groups.
      RESULTS: A total of 25 consecutive patients with 27 VBDAs were included.
      Seventeen VBDAs were treated by PAO, and 11 VBDAs were treated with FDs.
      Immediate total occlusion rate after initial treatment was higher in the PAO
      group than in the FD group (62.5% v.s. 9.1%, p = .018). Complete occlusion on
      follow-up at 18 months was more frequently observed in the PAO group (81.8%)
      compared to the FD group (55.6%), although the difference was not statistically
      significant (p = .433). Procedure related complication rate and mortality for the
      whole case series was 28% and 24% respectively, and were comparable in the two
      groups. Excellent outcome at discharge was achieved in 77.8% and 40% of patients
      treated with FD and PAO respectively, which was not statistically significant (p
      = .169). Excellent outcome at followed-up was comparable as well. CONCLUSIONS:
      PAO and FD treatment are both feasible options for treatment of VBDAs. PAO
      provide higher immediate complete occlusion rate compared to FD. Despite low
      initial complete occlusion rates, FD group presented a comparable long-term
      outcome and similar perioperative events rate compared to the PAO group.

PMID- 29362154
TI  - Model for improved correlation of BMD values between abdominal routine Dual
      energy CT data and DXA scans.
AB  - BACKGROUND: Osteoporosis is a common but underdiagnosed and undertreated disease
      causing severe morbidity and economic burden. The gold standard for detection of
      osteoporosis is DXA (dual energy x-ray absorptiometry), which is a dedicated
      examination for osteoporosis. Dual energy CT (DECT) examinations are increasingly
      used in daily routine for a wide variety of diagnoses. In the present study, we
      wanted to examine whether vBMD (volume bone mass density) could be evaluated as a
      side product in non-contrast as well as contrast phases as well as to evaluate a
      correction model taking known shortcomings for DXA into account. METHODS: A total
      of 20 patients, i.e. 79 vertebrae (one excluded due to vertebral fracture), mean
      age 71 years (range 43-85) with a mean BMI (body mass index) of 26 (range 17-33)
      were examined with both abdominal/pelvic DECT as well as DXA. Furthermore, aortic
      calcium was measured as well as the presence of osteoarthritis of the spine (OAS)
      and osteoarthritis in facet joints (OAF) with a 5-grade scaling system. RESULTS:
      A significant correlation was found between DXA BMD and vBMD from DECT with no
      contrast (WNC) (r = 0.424, p = 0.001), and with venous contrast (WVC) (r = 0.402,
      p < 0.001), but no significant correlation was found with arterial contrast
      (WAC). Using multivariate linear regression with DXA BMD as dependent, two models
      were created combining DECT WNC, aortic calciumscore (ACS), OAS and BMI yielding
      an R2 = 0.616 (model 1) and replacement of WNC to WVC a R2 = 0.612 (model 2). The
      Pearson correlation between DXA and predictive DXA BMD value of model 1 was r =
      0.785 (p < 0.001) and model 2 r = 0.782 (p < 0.001). CONCLUSION: There is a
      correlation between DXA BMD and DECT in non-contrast and venous contrast scans
      but not in arterial scans. The correlation is further improved by quantifying the
      degree of different confounding factors (osteoarthritis of the spine, body mass
      index and aortic calcium score) and taking these into account in an explanatory
      model. Future software solutions with DECT data as input data might be able to
      automatically measure the BMD in the trabecular bone as well as measuring the
      confounding factors automatically in order to obtain spinal DXA comparable BMD
      values.

PMID- 29362155
TI  - Pseudoexfoliation syndrome without glaucoma: White matter abnormalities detected
      by conventional MRI and diffusion tensor imaging.
AB  - PURPOSE: To assess macro- and microstructural brain changes in patients with
      pseudoexfoliation syndrome (PXS). MATERIALS AND METHODS: Comprehensive ophthalmic
      examination and brain MRI were conducted on 20 patients with PXS without glaucoma
      (aged 62.75 +/- 0.4 years) and 20 controls (aged 62 +/- 0.6 years). White matter
      (WM) integrity was evaluated on FLAIR and single-shot multisection SE-EPI
      diffusion tensor imaging (DTI) sequences. The presence and the number of white
      matter hyperintensities (WMHIs) on FLAIR images was compared between all patients
      and control subjects. Microstructural WM changes on DTI was evaluated using Tract
      based spatial statistics (TBSS). DTI metrics of the optic tracts were assessed by
      the region-of-interest (ROI) method. RESULTS: A significantly higher number of
      WMHIs was found in the patients with PXS than in the control subjects (P <=
      0.002). On DTI the patients showed bilateral increase in the mean diffusivity
      (MD), axial diffusivity (AD) and radial diffusivity (RD) values in the anterior
      thalamic radiation, the inferior fronto-occipital fasciculus, the superior
      longitudinal fasciculus, the inferior longitudinal fasciculus and the forceps
      minor. TBSS revealed no significant difference in fractional anisotropy (FA)
      values, but ROIs analysis of the optic tracts revealed decreased FA values in the
      patients. CONCLUSION: MRI in patients with PXS detects abnormalities in the brain
      and the optic tracts at a subclinical stage. Early detection of microstructural
      changes could be useful to guide appropriate treatment to impede the disease
      process.

PMID- 29362157
TI  - Contrast-enhanced cone-beam breast-CT: Analysis of optimal acquisition time for
      discrimination of breast lesion malignancy.
AB  - OBJECTIVE: To investigate the optimal acquisition time of contrast-enhanced cone
      beam breast-CT (CBBCT) for best discrimination of breast lesion malignancy and
      whether contrast enhancement can aid in classification of tumor histology.
      MATERIAL AND METHODS: The study included patients with BI-RADS 4 or 5 lesions
      identified on mammography and/or ultrasound. All patients were examined by non
      contrast (NC-CBBCT) and contrast-enhanced CBBCT (CE-CBBCT) at 2 and 3min after
      contrast media (CM) injection. Lesion enhancement of suspicious breast lesions
      was evaluated in corresponding CBBCT slices. RESULTS: A total of 31 patients with
      57 breast lesions, 30 malignant and 27 benign, were included. Malignant breast
      lesions demonstrated higher contrast enhancement than benign breast lesions at
      both 2min and 3min CE-CBBCT (2min: 48.17 vs. 0.3 HU, p<0.001; 3min: 57.38 vs.
      15.43 HU, p<0.001). Enhancement differences between malignant and benign breast
      lesions were largest at 2min CE-CBBCT. Ductal carcinoma in situ (DCIS) showed
      highest mean contrast enhancement among malignant breast lesions (100.93 HU at
      3min CE-CBBCT, p=0.0314) compared to invasive carcinoma of no special type with
      DCIS component (55.82 HU at 3min CE-CBBCT) and invasive ductal carcinoma (52.31
      HU at 3min CE-CBBCT). CONCLUSIONS: The contrast enhancement on CE-CBBCT best
      discriminates between malignant and benign breast lesions at 2min after CM
      injection. The enhancement has the potential to differentiate histopathological
      subtypes, with highest enhancement among malignant lesions seen for DCIS.

PMID- 29362156
TI  - Value of contrast-enhanced ultrasound and PET/CT in assessment of extramedullary
      lymphoma.
AB  - OBJECTIVE: The aim of the study was to evaluate clinical value of contrast
      enhanced ultrasonography (CEUS) and PET/CT for assessment of extramedullary
      lymphoma, using histopathology as reference standard. METHOD: A total of 63
      patients with histopathologically-confirmed extramedullary lymphoma who had
      underwent CEUS and PET/CT examinations of suspicious lymph nodes included in the
      study. CEUS patterns and parameters (arrival time, peak time and intensity, base
      intensity, area under the time-intensity curve, ascending and descending slopes)
      and PET/CT parameters including maximum standardized uptake value, mean
      standardized uptake value, and metabolic tumor volume (MTV) were evaluated.
      Patients were classified into Hodgkin lymphomas (HL), non-Hodgkin lymphomas
      (NHL), early (stage I and II) and advanced (stage III and IV) lymphoma, B cells
      and T cells lymphoma, and aggressive and indolent lymphoma. The differences
      between the two independent samples were compared using non-parametric rank and
      inspection, P < 0.05 was considered statistically significant. The optimal cut
      off value for parameters was used to predict the staging and pathology using
      Receiver Operating Characteristic (ROC) curve analysis. RESULT: In the early and
      advanced group, the differences between ?T and ascending slope (AS) were
      statistically significant (p = 0.010, 0.024 < 0.05). Hodgkin lymphomas (HL) or
      non-Hodgkin lymphomas (NHL) results were determined by optimal cut-off value of
      AT and TP (p = 0.001, 0.001 < 0.05). Aggressive or indolent lymphoma were
      determined by optimal cut-off values of Color Doppler flow resistance index (P =
      0.001 < 0.05) and SUVmax (p = 0.001 < 0.05). There was no statistically
      significant difference between B and T cell lymphoma. And there was no
      statistically significant difference among the qualitative indexes. The optimal
      cutoff value for statistically significant indicators was calculated by ROC.
      CONCLUSION: The quantitative parameters of CEUS and SUVmax of PET/CT are proven
      useful in assessment of different clinical and pathologic patterns of
      extramedullary lymphoma.

PMID- 29362159
TI  - New team, same objectives.

PMID- 29362158
TI  - Imaging giant cell arteritis and Aortitis in contrast enhanced 18F-FDG PET/CT:
      Which imaging score correlates best with laboratory inflammation markers?
AB  - PURPOSE: To define the most appropriate imaging parameters in combined
      Fluorodeoxyglucose (FDG) PET/CT reflecting the inflammatory burden in large
      vessel vasculitis. METHODS: Two readers retrospectively graded disease extent and
      activity in 17 LVV patients using visual and quantitative scores in FDG PET and
      contrast enhanced CT. Visual PET scores were assessed corresponding to FDG-uptake
      vs. liver uptake (score 0-3). CT visual scoring referred to the affected vessel
      extent (score 1-5). Quantitative PET scores relied on normalized SUV ratios. For
      quantitative CT evaluation vessel wall thickness was correlated with FDG- uptake.
      Imaging scores were correlated with Erythrocyte Sedimentation Rate (ESR) and C
      reactive protein (CRP). Intraclass correlation coefficients (ICC) were measured
      for interreader reliability. RESULTS: Visual PET scores showed stronger
      correlation with CRP (rho 0.640, 0.541 for reader I and II, respectively) than
      with ESR levels (rho 0.477, 0.447). Quantitative PET showed strongest correlation
      with CRP using liver as reference tissue. Visual CT scores did neither correlate
      with ESR nor with CRP levels (ESR: rho 0.085, 0.294 with p 0.743, 0.252; CRP: rho
      0.322, 0.395 with p 0.208, 0.116). Quantitative CT evaluation correlated with ESR
      levels in one reader (rho 0.505, -0.026), however no correlation between
      quantitative CT measures and quantitative PET scores was found. Best ICC between
      readers was 0.994 for highest SUVavg vessel/highest SUVavg liver. CONCLUSIONS:
      Visual and quantitative PET scores were superior to CT scores with best ICC and
      strongest correlations between quantitative PET score and inflammation markers
      especially when using vessel to liver ratios.

PMID- 29362160
TI  - Vive la difference! France's new guidelines on hospital-acquired pneumonia.

PMID- 29362161
TI  - Checklists and cognitive aids in simulation training and daily critical care
      practice: Simple tools to improve medical performance and patient outcome.

PMID- 29362162
TI  - Is augmented renal clearance the Holy Grail of antibiotic therapy failure in
      ventilator-acquired pneumonia?

PMID- 29362163
TI  - Vaccination program, health-workers mobilisation, public information: The lessons
      to learn from the flu outbreak in the Reunion Island.

PMID- 29362164
TI  - I (Influenza) will be back!

PMID- 29362165
TI  - Preoperative Detailed Coagulation Tests Are Required in Patients With Noonan
      Syndrome.
AB  - PURPOSE: Patients with Noonan syndrome often require surgery at young ages. They
      are at high risk of perioperative bleeding from coagulation defects that might
      not have been detected by routine screening. These risks are rarely described in
      the oral and maxillofacial surgery (OMS) literature. The aim of this study was to
      evaluate the perioperative bleeding risks associated with Noonan syndrome and to
      propose preoperative guidelines. MATERIALS AND METHODS: This report describes a
      retrospective case series of patients with Noonan syndrome who underwent OMS
      procedures during a continuous observational period (2013 through 2016) in the
      authors' center. Clinical data, blood screening test results, and perioperative
      bleeding were analyzed. RESULTS: Five patients (age, 4 to 20 yr) with Noonan
      syndrome who underwent OMS procedures were included in this study. One patient
      presented a spontaneous bleeding tendency (epistaxis requiring cauterization).
      Blood screening showed clotting defects in 3 patients. One patient presented
      abnormal perioperative bleeding owing to a mild defect in factor XI. CONCLUSION:
      Patients with Noonan syndrome must be referred to a hematologist for specific
      preoperative investigations and for adapted perioperative management.

PMID- 29362166
TI  - Impact of Temporomandibular Joint Discectomy on Condyle Morphology: An Animal
      Study.
AB  - PURPOSE: Temporomandibular disorders lead to parafunctional activity that may
      alter bone remodeling of mandibular components. This animal study aimed to assess
      the impact of temporomandibular joint discectomy on condylar bone
      microarchitecture. MATERIALS AND METHODS: A total of 30 one-month-old Wistar rats
      were assessed and divided into 3 equal groups (2 test groups and 1 control group)
      of 10. The first test group underwent disc removal, the second test group
      underwent disc and condylar cartilage removal, and the 10 remaining rats were
      analyzed as sham-operated controls, following a split-mouth design. The rats were
      killed humanely 2 months after surgery, and the respective mandibles were scanned
      with micro-computed tomography for quantitative morphometric analysis. RESULTS:
      There were significant differences among the 3 groups analyzed (disc removal,
      disc and condylar cartilage removal, and sham-operated control) for bone volume
      fraction (ratio of bone volume to total volume, P = .044), structure model index
      (P < .001), fractal dimension (P = .024), and porosity (P = .023). In addition,
      operated and contralateral nonoperated sides significantly differed for all
      variables in at least 1 of the test groups (P < .05) but not in the control group
      (P > .05). CONCLUSIONS: Within the limitations of this study, our results suggest
      that discectomy may lead to alterations of the mandibular condylar morphology.

PMID- 29362168
TI  - Letter to the Editor: Getting Better Value out of Studies Examining Prompts for
      Stair Use.

PMID- 29362167
TI  - The Cost of Interventions to Increase Influenza Vaccination: A Systematic Review.
AB  - CONTEXT: Influenza vaccination rates remain below Healthy People 2020 goals. This
      project sought to systematically review economic evaluations of healthcare-based
      quality improvement interventions for improving influenza vaccination uptake
      among general populations and healthcare workers. EVIDENCE ACQUISITION: The
      databases MEDLINE, Econlit, Centre for Reviews & Dissemination, Greylit, and
      Worldcat were searched in July 2016 for papers published from January 2004 to
      July 2016. Eligible studies evaluated efforts by bodies within the healthcare
      system to encourage influenza vaccination by means of an organizational or
      structural change. For each study, program costs per enrollee and per additional
      enrollee vaccinated were derived (excluding vaccine costs, standardized to 2017
      U.S. dollars). Complete economic evaluations were examined when available.
      EVIDENCE SYNTHESIS: Of 2,350 records, 18 articles were eligible and described 29
      unique interventions. Most interventions improved vaccine uptake. Among 23
      interventions in general populations, the median program cost was $3.27
      (interquartile range, $0.82-$11.53) per enrollee and $50.78 (interquartile range,
      $27.85-$124.84) per additional enrollee vaccinated. Among ten complete economic
      evaluations in general populations, three studies reported net cost savings, four
      reported costs <$50,000 per quality-adjusted life year, and three reported costs
      <$60,000 per life saved. Among six interventions in healthcare workers, the
      median program cost was $8.09 (interquartile range, $5.03-$10.31) per worker
      enrolled and $125.24 (interquartile range, $96.06-$171.38) per additional worker
      vaccinated (there were no complete economic analyses). CONCLUSIONS: Quality
      improvement interventions for influenza vaccination involve per-enrollee costs
      that are similar to the cost of the vaccine itself ($11.78-$36.08/dose). Based on
      limited available evidence in general populations, quality improvement
      interventions may be cost saving to cost effective for the health system.

PMID- 29362169
TI  - Authors' Response to: "Getting Better Value out of Studies Examining Prompts for
      Stair Use".

PMID- 29362170
TI  - Envisioning the Future of Robotic Surgery: The Surgeon's Perspective.

PMID- 29362171
TI  - Long-Segment, Supercharged Pedicled Jejunal Interposition for Esophageal
      Replacement: How I Teach It.

PMID- 29362172
TI  - Invited Commentary.

PMID- 29362173
TI  - Invited Commentary.

PMID- 29362174
TI  - Invited Commentary.

PMID- 29362175
TI  - Invited Commentary.

PMID- 29362176
TI  - The Society of Thoracic Surgeons, The Society of Cardiovascular
      Anesthesiologists, and The American Society of ExtraCorporeal Technology:
      Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.
AB  - Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the
      evidence base surrounding the conduct of anticoagulation therapy for CPB has not
      been organized into a succinct guideline. For this and other reasons, there is
      enormous practice variability relating to the use and dosing of heparin,
      monitoring heparin anticoagulation, reversal of anticoagulation, and the use of
      alternative anticoagulants. To address this and other gaps, The Society of
      Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the
      American Society of Extracorporeal Technology developed an Evidence Based
      Workgroup. This was a group of interdisciplinary professionals gathered to
      summarize the evidence and create practice recommendations for various aspects of
      CPB. To date, anticoagulation practices in CPB have not been standardized in
      accordance with the evidence base. This clinical practice guideline was written
      with the intent to fill the evidence gap and to establish best practices in
      anticoagulation therapy for CPB using the available evidence. To identify
      relevant evidence, a systematic review was outlined and literature searches were
      conducted in PubMed using standardized medical subject heading (MeSH) terms from
      the National Library of Medicine list of search terms. Search dates were
      inclusive of January 2000 to December 2015. The search yielded 833 abstracts,
      which were reviewed by two independent reviewers. Once accepted into the full
      manuscript review stage, two members of the writing group evaluated each of 286
      full papers for inclusion eligibility into the guideline document. Ninety-six
      manuscripts were included in the final review. In addition, 17 manuscripts
      published before 2000 were included to provide method, context, or additional
      supporting evidence for the recommendations as these papers were considered
      sentinel publications. Members of the writing group wrote and developed
      recommendations based on review of the articles obtained and achieved more than
      two thirds agreement on each recommendation. The quality of information for a
      given recommendation allowed assessment of the level of evidence as recommended
      by the American College of Cardiology Foundation/American Heart Association Task
      Force on Practice Guidelines. Recommendations were written in the three following
      areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB;
      (2) heparin contraindications and heparin alternatives; and (3) reversal of
      anticoagulation during cardiac operations. It is hoped that this guideline will
      serve as a resource and will stimulate investigators to conduct more research and
      to expand on the evidence base on the topic of anticoagulation therapy for CPB.

PMID- 29362177
TI  - Reply.

PMID- 29362178
TI  - Aortic Dissection During Pregnancy or in the Postpartum Period: It All Starts
      With Clinical Recognition.

PMID- 29362179
TI  - Leaflet Perforation by Cor-Knot Automated Fasteners: More Usual Than You Think.

PMID- 29362180
TI  - Randomized Evidence on Perioperative Statin Therapy in Cardiac Surgery.

PMID- 29362181
TI  - Reply.

PMID- 29362182
TI  - Reply.

PMID- 29362183
TI  - Subcarinal Lymph Node Importance Revisited.

PMID- 29362184
TI  - Radiofrequency Bipolar Surgical Ablation for Atrial Fibrillation.

PMID- 29362185
TI  - Reply.

PMID- 29362186
TI  - Confounders Between Plasma Monocyte Chemotactic Protein-1 And Acute Kidney
      Injury.

PMID- 29362187
TI  - Factors Favoring Retrograde Type A Aortic Dissection After Endovascular Aortic
      Repair.

PMID- 29362188
TI  - Aortic Valve Therapy for Intermediate-Risk Patients: Let's Start With the Facts!

PMID- 29362189
TI  - Percutaneous Repair of Postoperative Mitral Regurgitation After Left Ventricular
      Assist Device Implant.
AB  - Mitral regurgitation commonly improves after implantation of a left ventricular
      assist device without concomitant valvular repair owing to the mechanical
      unloading of the left ventricle. However, the development (or persistence) of
      significant mitral regurgitation after implantation of a left ventricular assist
      device is associated with adverse clinical events. We present a case of a left
      ventricular assist device patient who successfully underwent a percutaneous
      MitraClip procedure for repair of persistent late postoperative mitral
      insufficiency with demonstrable clinical and hemodynamic improvement.

PMID- 29362190
TI  - Which Antiplatelet Therapy in Patients With Left Ventricular Assist Device and
      Aspirin Allergy?
AB  - In patients with left ventricular assist device support and aspirin allergy, the
      choice of effective antiplatelet strategy remains a challenge. We compared the
      antithrombotic effect of clopidogrel vs ticagrelor in an LVAD patient with
      aspirin allergy by using a modified protocol of the thrombin generation test,
      accounting selectively for the platelet contribution on thrombin generation. Our
      results demonstrate enhanced antithrombotic efficacy offered by ticagrelor.
      Consistent with experimental results, the patient has passed more than 300 days
      without thromboembolic complications. This study provides additional mechanistic
      rationale supporting clinical evidence and opens the perspective to identify
      individual poor responsiveness to drugs by specifically evaluating drug-mediated
      platelet function.

PMID- 29362191
TI  - Sympathectomy for Stabilization of Heart Failure Due to Drug-Refractory
      Ventricular Tachycardia.
AB  - We describe the novel use of bilateral cardiac sympathectomy in a woman with end
      stage heart failure caused by ventricular tachycardia refractory to standard
      medical therapy who was under consideration for heart transplantation.
      Postoperatively, our patient has not experienced any symptoms of ventricular
      tachycardia, has returned to normal physical activity, and is no longer under
      consideration for transplantation as a result of the improvement in her cardiac
      function. Bilateral sympathectomy can be more effective than unilateral
      sympathectomy or percutaneous stellate ganglion blockade in patients with
      refractory ventricular tachycardia. Careful patient selection is necessary to
      identify patients who will benefit most from the procedure.

PMID- 29362192
TI  - Mitral Annular Calcification and Mitral Valve Replacement: A New Approach.
AB  - Mitral valve replacement is technically challenging in the context of mitral
      annular calcification. A new surgical strategy is described that was used in a 71
      year-old obese patient, where intraatrial prosthesis insertion and valve fixation
      into native uncalcified structures were performed without calcium debridement.

PMID- 29362193
TI  - Ascending Aortic Aneurysm in a Child With Fibulin-4 Deficiency.
AB  - EFEMP2 (alias FBLN4) encodes extracellular matrix protein fibulin-4, and its
      mutation is associated with autosomal recessive cutis laxa type 1B and leads to
      severe aortopathy with aneurysm formation and vascular tortuosity. A 4-month-old
      child presented with a large ascending aortic aneurysm, and genetic testing
      revealed an EFEMP2 mutation. We achieved successful repair of the ascending
      aortic aneurysm at 33 months of age and report the macroscopic and microscopic
      findings.

PMID- 29362194
TI  - Coronary Button Pseudoaneurysms After Aortic Root Replacement in a Child With
      Loeys-Deitz Syndrome.
AB  - Loeys-Deitz syndrome (LDS) is a connective tissue disorder characterized by
      aggressive aortopathy with a proclivity for aortic aneurysmal rupture and
      dissection. Prophylactic surgical intervention is often indicated to ameliorate
      risk of aneurysm rupture. Aortic root replacement involves excision of the
      coronary arteries from the aortic root with a button of surrounding aortic tissue
      and subsequent anastomosis of these buttons to the synthetic aortic graft. We
      report the case of a 16-year-old girl with LDS who developed pseudoaneurysms at
      the sites of previous coronary button implantation.

PMID- 29362195
TI  - Single Ostium of the Right and Left Coronary Artery From the Right Pulmonary
      Artery.
AB  - We describe a newborn with single-ventricle malformation and anomalous origin of
      both coronary arteries from single ostium in the middle portion of the right
      pulmonary artery whose coronary anatomy was discovered during the operation and
      who underwent successful staged operative management. This report presents a
      unique anatomic association, proposes a means of management, and highlights the
      importance of intraoperative analysis.

PMID- 29362196
TI  - Fatal Hemoptysis After Closure of Gastrobronchial Fistula Using an Amplatzer
      Vascular Device.
AB  - The Amplatzer family of vascular devices has been used off-label for the
      treatment of complex gastrointestinal and airway fistulas. We report a case in
      which closure of a benign gastrobronchial fistula with the use of an Amplatzer
      device resulted in massive hemoptysis and death.

PMID- 29362198
TI  - Surgical Management of Chyloptysis.
AB  - Chyloptysis is a rare clinical presentation. Diagnosis is challenging and
      requires recognition of milky-sputum or bronchial casts. We describe a case of
      chyloptysis secondary to thoracic lymphangiectasia that necessitated surgical
      ligation of the main thoracic duct and accessory branches. The patient had no
      postoperative complications, and at 6-month follow-up remained symptom-free. A
      paucity of literature describes the management of chyloptysis. We review
      diagnosis, treatment considerations and operative principles.

PMID- 29362197
TI  - Immunoglobulin G4-Related Disease Mimicking an Anterior Mediastinal Tumor.
AB  - Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated collection of
      disorders that were once thought to be unrelated but are increasingly being
      recognized as a single entity. The tumor-like swelling of the involved organ, a
      storiform pattern of fibrosis, and a serologic elevation of IgG4 can lead to the
      diagnosis of IgG4-RD. The usual organs affected are the pancreas, biliary tract,
      and salivary and lacrimal glands. There have been few reports of intrathoracic
      cases, which usually have pulmonary lesions. We here report a case of IgG4-RD of
      the anterior mediastinum in the form of a mass, a rare entity, the second such
      patient described in the literature to date.

PMID- 29362199
TI  - Tracheobronchopathia Osteochondroplastica as a Single Mass in Lingular Bronchus.
AB  - We describe a rare case of tracheobronchopathia osteochondroplastica (TBO) in a
      35-year-old man who presented with recurrent chest infection and hemoptysis.
      Bronchoscopy and computed tomography scan revealed a single 1.5-cm hard nodular
      mass lesion in the lingular bronchus associated with collapse and bronchiectasis
      of the lingula. The patient underwent open left lingulectomy with removal of the
      mass. Histopathology of the lesion showed characteristic features of TBO. TBO is
      generally characterized by multiple nodules in the trachea or main bronchi. The
      presentation of TBO as a single dominant mass is rare and can be considered as a
      differential diagnosis for intrabronchial calcified mass lesions.

PMID- 29362200
TI  - Pleural Metastasis of Osteosarcoma.

PMID- 29362201
TI  - Bilateral Arterial Ducts Causing Airway Compression by a Vascular Ring.

PMID- 29362202
TI  - Ross-Konno for Interrupted Aortic Arch: Simplified Arch Reconstruction Using
      Swing-Back Technique.
AB  - In neonates with interrupted aortic arch and severe left ventricular outflow
      tract obstruction full relief of left ventricular outflow tract obstruction and
      adequate aortic arch repair is required. It has been shown that neonatal Ross
      Konno provides adequate and durable relieve of left ventricular outflow tract
      gradient. Additional aortic arch repair using the swing-back technique provides a
      simplified reconstruction of the arch with a tension-free, direct anastomosis. We
      describe the technique and results of our experience in 3 neonates.

PMID- 29362203
TI  - Novel Leg Cannula for Venous Decompression in Peripheral Extracorporeal Membrane
      Oxygenation.
AB  - A chimney femoral artery graft for peripheral extracorporeal membrane oxygenation
      can potentially cause hyperperfusion and subsequent venous congestion in the
      ipsilateral leg, especially in the context of septic shock and higher flow
      requirement. This report describes a novel technique to use an additional leg
      venous cannula to avoid leg congestion as well as to achieve higher total flow.

PMID- 29362204
TI  - Analysis of public policies in favor of the elderly people in Senegal: state of
      legal protection.
AB  - Senegal will be spared by phenomenon of population ageing, which will surely have
      socioeconomic and cultural consequences that will not be easy to tackle, as all
      sectors will be affected. In regard to legal protection, there are not any
      special legal acts for the elderly as is the case for children and women. They
      are treated just as responsible adults whose legal status is the same as everyone
      else. As far as the framework of legal protection of elderly people is concerned,
      Senegal has ratified all international and regional means and mecanisms for the
      protection of the rights of the elderly. In addition, the authorities have
      adopted policies and programs that favor taking charge of old people's interests.
      At the present, Senegal possesses a legal framework for the protection of its
      elderly people. So the matter is about creating new rights, because even the
      existing rights are not known to their beneficiaries. What is important is to
      ensure that the elderly fully enjoy their rights in the same way as the other
      members of society. It is wise, therefore, to put in place plan for information,
      public awareness and communication concerning the legal regulating framework.
      Thus, Senegal could be regarded as a pioneer in terms of the protection the
      elderly, and these leading programs can represent models for the countries of the
      region, whose social, sanitary and economic contexts are similar.

PMID- 29362205
TI  - Testimonials and Informational Videos on Branded Prescription Drug Websites:
      Experimental Study to Assess Influence on Consumer Knowledge and Perceptions.
AB  - BACKGROUND: Direct-to-consumer (DTC) promotion of prescription drugs can affect
      consumer behaviors and health outcomes, and Internet drug promotion is growing
      rapidly. Branded drug websites often capitalize on the multimedia capabilities of
      the Internet by using videos to emphasize drug benefits and characteristics.
      However, it is unknown how such videos affect consumer processing of drug
      information. OBJECTIVE: This study aimed to examine how videos on prescription
      drug websites, and the inclusion of risk information in those videos, influence
      consumer knowledge and perceptions. METHODS: We conducted an experimental study
      in which online panel participants with acid reflux (n=1070) or high blood
      pressure (n=1055) were randomly assigned to view 1 of the 10 fictitious
      prescription drug websites and complete a short questionnaire. On each website,
      we manipulated the type of video (patient testimonial, mechanism of action
      animation, or none) and whether the video mentioned drug risks. RESULTS:
      Participants who viewed any video were less likely to recognize drug risks
      presented only in the website text (P<=.01). Including risk information in videos
      increased participants' recognition of the risks presented in the videos
      (P<=.01). However, in some cases, including risk information in videos decreased
      participants' recognition of the risks not presented in the videos (ie, risks
      presented in text only; P<=.04). Participants who viewed a video without drug
      risk information thought that the website placed more emphasis on benefits,
      compared with participants who viewed the video with drug risk information
      (P<=.01). Compared with participants who viewed a video without drug risk
      information, participants who viewed a video with drug risk information thought
      that the drug was less effective in the high blood pressure sample (P=.03) and
      thought that risks were more serious in the acid reflux sample (P=.01). There
      were no significant differences between risk and nonrisk video conditions on
      other perception measures (P>.05). In addition, we noted a few differences among
      the types of videos. CONCLUSIONS: Including risks in branded drug website videos
      may increase in-video risk retention at the expense of text-only risk retention.

PMID- 29362206
TI  - Paper- or Web-Based Questionnaire Invitations as a Method for Data Collection:
      Cross-Sectional Comparative Study of Differences in Response Rate, Completeness
      of Data, and Financial Cost.
AB  - BACKGROUND: Paper questionnaires have traditionally been the first choice for
      data collection in research. However, declining response rates over the past
      decade have increased the risk of selection bias in cross-sectional studies. The
      growing use of the Internet offers new ways of collecting data, but trials using
      Web-based questionnaires have so far seen mixed results. A secure, online digital
      mailbox (e-Boks) linked to a civil registration number became mandatory for all
      Danish citizens in 2014 (exemption granted only in extraordinary cases).
      Approximately 89% of the Danish population have a digital mailbox, which is used
      for correspondence with public authorities. OBJECTIVE: We aimed to compare
      response rates, completeness of data, and financial costs for different
      invitation methods: traditional surface mail and digital mail. METHODS: We
      designed a cross-sectional comparative study. An invitation to participate in a
      survey on help-seeking behavior in out-of-hours care was sent to two groups of
      randomly selected citizens from age groups 30-39 and 50-59 years and parents to
      those aged 0-4 years using either traditional surface mail (paper group) or
      digital mail sent to a secure online mailbox (digital group). Costs per
      respondent were measured by adding up all costs for handling, dispatch, printing,
      and work salary and then dividing the total figure by the number of respondents.
      Data completeness was assessed by comparing the number of missing values between
      the two methods. Socioeconomic variables (age, gender, family income, education
      duration, immigrant status, and job status) were compared both between
      respondents and nonrespondents and within these groups to evaluate the degree of
      selection bias. RESULTS: A total 3600 citizens were invited in each group; 1303
      (36.29%) responded to the digital invitation and 1653 (45.99%) to the paper
      invitation (difference 9.66%, 95% CI 7.40-11.92). The costs were ?1.51 per
      respondent for the digital group and ?15.67 for paper group respondents. Paper
      questionnaires generally had more missing values; this was significant in five of
      17 variables (P<.05). Substantial differences were found in the socioeconomic
      variables between respondents and nonrespondents, whereas only minor differences
      were seen within the groups of respondents and nonrespondents. CONCLUSIONS:
      Although we found lower response rates for Web-based invitations, this solution
      was more cost-effective (by a factor of 10) and had slightly lower numbers of
      missing values than questionnaires sent with paper invitations. Analyses of
      socioeconomic variables showed almost no difference between nonrespondents in
      both groups, which could imply that the lower response rate in the digital group
      does not necessarily increase the level of selection bias. Invitations to
      questionnaire studies via digital mail may be an excellent option for collecting
      research data in the future. This study may serve as the foundational pillar of
      digital data collection in health care research in Scandinavia and other
      countries considering implementing similar systems.

PMID- 29362207
TI  - Web-based Therapy Plus Support by a Coach in Depressed Patients Referred to
      Secondary Mental Health Care: Randomized Controlled Trial.
AB  - BACKGROUND: The evidence for the effectiveness of Web-based therapies comes
      mainly from nonclinical populations, with a few studies in primary care. There is
      little evidence from patients referred to secondary mental health care with
      depression. Adherence to Web-based therapies is often poor. One way to increase
      this is to create a new health service role of a coach to guide people through
      the therapy. OBJECTIVE: This study aimed to test in people referred to secondary
      care with depression if a Web-based therapy (The Journal) supported by a coach
      plus usual care would be more effective in reducing depression compared with
      usual care plus an information leaflet about Web-based resources after 12 weeks.
      METHODS: We conducted a randomized controlled trial with two parallel arms and a
      process evaluation that included structured qualitative interviews analyzed using
      thematic analysis. The coach had a background in occupational therapy.
      Participants were recruited face-to-face at community mental health centers.
      RESULTS: We recruited 63 people into the trial (intervention 35, control 28).
      There were no statistically significant differences in the change from baseline
      in Patient Health Questionnaire-9 (PHQ-9) scores at 12 weeks comparing The
      Journal with usual care (mean change in PHQ-9 score 9.4 in the intervention group
      and 7.1 in the control group, t41=1.05, P=.30; mean difference=2.3, 95% CI -2.1
      to 6.7). People who were offered The Journal attended on average about one less
      outpatient appointment compared with usual care, although this difference was not
      statistically significant (intervention mean number of visits 2.8 (SD 5.5)
      compared with 4.1 (SD 6.7) in the control group, t45=-0.80, P=.43; mean
      difference=1.3, 95% CI -4.5 to 2.0). The process evaluation found that the mean
      number of lessons completed in the intervention group was 2.5 (SD=1.9; range=0-6)
      and the number of contacts with the coach was a mean of 8.1 (SD=4.4; range=0-17).
      The qualitative interviews highlighted the problem of engaging clinicians in
      research and their resistance to recruitment: technical difficulties with The
      Journal, which prevented people logging in easily; difficulty accessing The
      Journal as it was not available on mobile devices; participants finding some
      lessons difficult; and participants saying they were too busy to complete the
      sessions. CONCLUSIONS: The study demonstrated that it is feasible to use a coach
      in this setting, that people found it helpful, and that it did not conflict with
      other care that participants were receiving. Future trials need to engage
      clinicians at an early stage to articulate where Web-based therapies fit into
      existing clinical pathways; Web-based therapies should be available on mobile
      devices, and logging in should be easy. The role of the coach should be explored
      in larger trials. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry (ACTRN): 12613000015741;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363351&isReview=
      rue (Archived by WebCite at http://www.webcitation.org/6wEyCc6Ss).

PMID- 29362208
TI  - Youth Codesign of a Mobile Phone App to Facilitate Self-Monitoring and Management
      of Mood Symptoms in Young People With Major Depression, Suicidal Ideation, and
      Self-Harm.
AB  - BACKGROUND: Effective treatment of depression in young people is critical, given
      its prevalence, impacts, and link to suicide. Clinical practice guidelines point
      to the need for regular monitoring of depression symptom severity and the
      emergence of suicidal ideation to track treatment progress and guide intervention
      delivery. Yet, this is seldom integrated in clinical practice. OBJECTIVE: The
      objective of this study was to address the gap between guidelines about
      monitoring and real-world practice by codesigning an app with young people that
      allows for self-monitoring of mood and communication of this monitoring with a
      clinician. METHODS: We engaged young people aged 18 to 25 years who had
      experienced depression, suicidal ideation including those who self-harm, as well
      as clinicians in a codesign process. We used a human-centered codesign design
      studio methodology where young people designed the features of the app first
      individually and then as a group. This resulted in a minimal viable product
      design, represented through low-fidelity hand-drawn wireframes. Clinicians were
      engaged throughout the process via focus groups. RESULTS: The app incorporated a
      mood monitoring feature with innovative design aspects that allowed
      customization, and was named a "well-being tracker" in response to the need for a
      positive approach to this function. Brief personalized interventions designed to
      support young people in the intervals between face-to-face appointments were
      embedded in the app and were immediately available via pop-ups generated by a
      back-end algorithm within the well-being tracker. Issues regarding the safe
      incorporation of alerts generated by the app into face-to-face clinical services
      were raised by clinicians (ie, responding in a timely manner) and will need to be
      addressed during the full implementation of the app into clinical services.
      CONCLUSIONS: The potential to improve outcomes for young people via technology
      based enhancement to interventions is enormous. Enhancing communication between
      young people and their clinicians about symptoms and treatment progress and
      increasing access to timely and evidence-based interventions are desirable
      outcomes. To achieve positive outcomes for young people using technology- (app)
      based interventions, it is critical to understand and incorporate, in a
      meaningful way, the expectations and motivations of both young people and
      clinicians.

PMID- 29362209
TI  - Evaluation of an mHealth App (DeStressify) on University Students' Mental Health:
      Pilot Trial.
AB  - BACKGROUND: One in five Canadians experience mental health issues with those in
      the age range of 15 to 24 years being most at risk of a mood disorder. University
      students have shown significantly higher rates of mental health problems than the
      general public. Current university support services are limited by factors such
      as available staff and finances, and social stigma has frequently been identified
      as an additional barrier that prevents students from accessing these resources.
      Mobile health (mHealth) apps are one form of alternative health support that is
      discrete and accessible to students, and although they are recognized as a
      promising alternative, there is limited research demonstrating their efficacy.
      OBJECTIVE: The aim of this study was to evaluate a mindfulness-based app's
      ("DeStressify") efficacy on stress, anxiety, depressive symptomology, sleep
      behavior, work or class absenteeism, work or school productivity, and quality of
      life (QoL) among university students. METHODS: Full-time undergraduate students
      at a Canadian university with smartphones and Internet access were recruited
      through in-class announcements and on-campus posters. Participants randomized
      into an experimental condition were given and instructed to use the DeStressify
      app 5 days a week for 4 weeks. Control condition participants were wait-listed.
      All participants completed pre- and postintervention Web-based surveys to self
      assess stress, anxiety, depressive symptomatology, sleep quality, and health
      related QoL. RESULTS: A total of 206 responses were collected at baseline, with
      163 participants completing the study (86 control, 77 experimental). Using
      DeStressify was shown to reduce trait anxiety (P=.01) and improve general health
      (P=.001), energy (P=.01), and emotional well-being (P=.01) in university
      students, and more participants in the experimental condition believed their
      productivity improved between baseline and postintervention measurements than the
      number of participants expected to believe so randomly by chance (P=.01). The app
      did not significantly improve stress, state anxiety, physical and social
      functioning, and role limitations because of physical or emotional health
      problems or pain (P>.05). CONCLUSIONS: Mindfulness-based apps may provide an
      effective alternative support for university students' mental health.
      Universities and other institutions may benefit from promoting the use of
      DeStressify or other mindfulness-based mHealth apps among students who are
      interested in methods of anxiety management or mindfulness-based self-driven
      health support. Future steps include examining DeStressify and similar mHealth
      apps over a longer period and in university staff and faculty.

PMID- 29362210
TI  - Concussion Assessment With Smartglasses: Validation Study of Balance Measurement
      Toward a Lightweight, Multimodal, Field-Ready Platform.
AB  - BACKGROUND: Lightweight and portable devices that objectively measure concussion
      related impairments could improve injury detection and critical decision-making
      in contact sports and the military, where brain injuries commonly occur but
      remain underreported. Current standard assessments often rely heavily on
      subjective methods such as symptom self-reporting. Head-mounted wearables, such
      as smartglasses, provide an emerging platform for consideration that could
      deliver the range of assessments necessary to develop a rapid and objective
      screen for brain injury. Standing balance assessment, one parameter that may
      inform a concussion diagnosis, could theoretically be performed quantitatively
      using current off-the-shelf smartglasses with an internal accelerometer. However,
      the validity of balance measurement using smartglasses has not been investigated.
      OBJECTIVE: This study aimed to perform preliminary validation of a smartglasses
      based balance accelerometer measure (BAM) compared with the well-described and
      characterized waist-based BAM. METHODS: Forty-two healthy individuals (26 male,
      16 female; mean age 23.8 [SD 5.2] years) participated in the study. Following the
      BAM protocol, each subject performed 2 trials of 6 balance stances while
      accelerometer and gyroscope data were recorded from smartglasses (Glass Explorer
      Edition). Test-retest reliability and correlation were determined relative to
      waist-based BAM as used in the National Institutes of Health's Standing Balance
      Toolbox. RESULTS: Balance measurements obtained using a head-mounted wearable
      were highly correlated with those obtained through a waist-mounted accelerometer
      (Spearman rho, rho=.85). Test-retest reliability was high (intraclass correlation
      coefficient, ICC2,1=0.85, 95% CI 0.81-0.88) and in good agreement with waist
      balance measurements (ICC2,1=0.84, 95% CI 0.80-0.88). Considering the normalized
      path length magnitude across all 3 axes improved interdevice correlation
      (rho=.90) while maintaining test-retest reliability (ICC2,1=0.87, 95% CI 0.83
      0.90). All subjects successfully completed the study, demonstrating the
      feasibility of using a head-mounted wearable to assess balance in a healthy
      population. CONCLUSIONS: Balance measurements derived from the smartglasses-based
      accelerometer were consistent with those obtained using a waist-mounted
      accelerometer. Additional research is necessary to determine to what extent
      smartglasses-based accelerometry measures can detect balance dysfunction
      associated with concussion. However, given the potential for smartglasses to
      perform additional concussion-related assessments in an integrated, wearable
      platform, continued development and validation of a smartglasses-based balance
      assessment is warranted. This approach could lead to a wearable platform for real
      time assessment of concussion-related impairments that could be further augmented
      with telemedicine capabilities to integrate professional clinical guidance.
      Smartglasses may be superior to fully immersive virtual reality headsets for this
      application, given their lighter weight and reduced likelihood of potential
      safety concerns.

PMID- 29362211
TI  - Prevalence of Health App Use Among Older Adults in Germany: National Survey.
AB  - BACKGROUND: Health apps are increasingly becoming an integral part of health
      care. Especially in older adults, the self-management of chronic diseases by
      health apps might become an integral part of health care services. OBJECTIVE: The
      aim of this explorative study was to investigate the prevalence of health app use
      and related demographic factors, as well as health status among older adults in
      Germany. METHODS: A nationwide postal survey was conducted. Of the 5000
      individuals contacted, a total of 576 participants completed this survey. On the
      basis of their self-indicated assignment to one of the three predefined user
      groups (health app users, general app users, and nonusers of apps), participants
      answered various questions regarding app and health app use, including frequency
      of use and number of installed apps, demographic factors, and health status.
      RESULTS: In total, 16.5% (95/576) used health apps, whereas 37.5% (216/576)
      indicated only using general apps, and 46.0% (265/576) reported using no apps at
      all. The number of installed health apps was most frequently reported as between
      1 and 5 apps per participant, which were usually used on a weekly basis. The most
      frequently cited type of health apps were exercise-related ones. Individuals
      using health apps were found to be younger (MeanmHealth 66.6, SD 4.7) and to have
      a higher level of technical readiness compared with general app users and
      nonusers of apps (adjusted odds ratio, AOR=4.02 [95% CI 2.23-7.25] for technical
      readiness, and AOR=0.905 [95% CI 0.85-0.97] for age). The most frequently
      mentioned sources of information about apps within the group of health and
      general app users were family and friends. Identified barriers against the use of
      health apps were a lack of trust, data privacy concerns, and fear of
      misdiagnosis. CONCLUSIONS: Health apps are already used by older adults in
      Germany. The main type of apps used are exercise-related ones. Barriers to and
      incentives for the use of health apps and associations with health status and
      users' demographics were revealed.

PMID- 29362212
TI  - How Experts' Use of Medical Technical Jargon in Different Types of Online Health
      Forums Affects Perceived Information Credibility: Randomized Experiment With
      Laypersons.
AB  - BACKGROUND: Online health forums are widely used, but the quality of advice
      differs as much as the knowledge backgrounds of the audience members who receive
      the advice. It is important to understand how people judge the information given
      online. In line with the communication accommodation theory (CAT), online forums
      represent specific social contexts of communication which can present either
      accommodative or nonaccommodative language to an audience. Accordingly, use of
      accommodative or nonaccommodative language might affect people's perceived trust
      in the communicator. OBJECTIVE: The objective of this study was to investigate
      how experts who use accommodative (vs nonaccommodative) language are evaluated by
      passive users of an online forum. METHODS: Participants (n=98) took part in an
      online experiment and read experts' posts about 10 nutrition myths. Following a 2
      x 2 mixed design, experts' posts were written using either low or high amounts of
      medical technical jargon (MTJ) (within factor) and were directed at different
      audiences (mainly other medical experts [in a professional forum] vs a user group
      mainly comprising laypersons [in an advisory forum]) (between factor).
      Accommodation occurred where experts used high amounts of MTJ to address other
      medical experts in the professional forum; it also occurred when experts used low
      amounts of MTJ to address laypersons in the advisory forum. Conversely,
      nonaccommodation occurred when experts used high amounts of MTJ in the advisory
      forum and low amounts of MTJ in the professional forum. In each condition,
      participants evaluated the credibility of the information, the trustworthiness of
      the experts, and the accommodation by the experts. RESULTS: Overall, participants
      judged the credibility of information to be higher when experts used MTJ that was
      accommodative to the designated audience, F1,95=3.10, P=.04, etap2=.031. In
      addition, participants judged the experts in professional forums to be more
      trustworthy than experts in advisory forums (all F1,96>=3.54, P <=.03,
      etap2>=.036). Moreover, participants rated experts who used high amounts of MTJ
      to have higher competence (F1,96=37.54, P<.001, etap2=.28], lower integrity
      (F1,96=10.77, P=.001, etap2=.101), and lower benevolence (F1,96=9.75, P=.002,
      etap2=.092), as well as to have lower perceived accommodation to the audience
      (all F1,96>=72.17, P<.001, etap2>=.43) compared with experts who used low MTJ.
      CONCLUSIONS: To provide health information online that is perceived as credible,
      experts should consider using similar language as the language used by the
      addressed audience. As it is often impossible to determine the exact makeup of an
      online audience, further research might investigate whether having experts
      explicitly declare which audience they intend to address can help people to more
      reliably assess an expert's trustworthiness. Furthermore, as people assess
      information differently depending on the context of online communication, it
      would be valuable for research to consider other aspects of the context beyond
      those of the audience.

PMID- 29362214
TI  - Routine enquiry for domestic violence and abuse in sexual health settings.

PMID- 29362213
TI  - Functional Knowledge of Pre-Exposure Prophylaxis for HIV Prevention Among
      Participants in a Web-Based Survey of Sexually Active Gay, Bisexual, and Other
      Men Who Have Sex With Men: Cross-Sectional Study.
AB  - BACKGROUND: Awareness of pre-exposure prophylaxis (PrEP) for HIV prevention is
      increasing, but little is known about the functional knowledge of PrEP and its
      impact on willingness to use PrEP. OBJECTIVE: The objective of this study was to
      assess the functional knowledge of PrEP among a sample of gay, bisexual, and
      other men who have sex with men (MSM) participating in a Web-based survey of
      sexually active MSM. METHODS: Men at least 18 years old, residing in the United
      States, and reporting sex with a man in the previous 6 months were recruited
      through social networking websites. PrEP functional knowledge included the
      following 4 questions (1) efficacy of consistent PrEP use, (2) inconsistent PrEP
      use and effectiveness, (3) PrEP and condom use, and (4) effectiveness at reducing
      sexually transmitted infections (STIs). Ordinal logistic regression was used to
      identify respondent characteristics associated with PrEP functional knowledge. In
      a subsample of participants responding to HIV prevention questions, we compared
      willingness to use PrEP by response to PrEP functional knowledge using logistic
      regression analysis adjusted for age, race and ethnicity, and education level.
      RESULTS: Among 573 respondents, PrEP knowledge was high regarding adherence
      (488/573, 85.2%), condom use (532/573, 92.8%), and STIs (480/573, 83.8%), but
      only 252/573 (44.0%) identified the correct efficacy. Lower functional PrEP
      knowledge was associated with minority race/ethnicity (P=.005), lower education
      (P=.01), and not having an HIV test in the past year (P=.02). Higher PrEP
      knowledge was associated with willingness to use PrEP (P=.009). Younger age was
      not associated with higher PrEP functional knowledge or willingness to use PrEP.
      CONCLUSIONS: PrEP knowledge was generally high in our study, including condom use
      and consistent use but may be lacking in higher risk MSM. The majority of
      respondents did not correctly identify PrEP efficacy with consistent use, which
      could impact motivation to seek out PrEP for HIV prevention. Targeted messaging
      to increase PrEP knowledge may increase PrEP use.

PMID- 29362215
TI  - Burns from illegal cannabis oil manufacturing: a case series.
AB  - BACKGROUND: The increasing consideration of cannabis legalization in Canada and
      the United States has motivated physicians to assess its prospective impact on
      the health care system. Health care providers in the burns community are
      concerned about injuries sustained as a result of the illegal manufacturing of
      cannabis oil because it involves highly flammable reagents. METHODS: We report a
      retrospective case series of patients with cannabis oil burns (identified by
      evidence of combustion during cannabis oil manufacturing) treated from April 2012
      to March 2014 at the Foothills Medical Centre in Calgary, Alberta, Canada. We
      compare the characteristics of these patients with those of patients admitted
      over the same period with any burns. RESULTS: We found that 12 (out of 161
      patients) admitted over the review period sustained burns from cannabis oil
      manufacturing. Compared with patients in the total burn group, patients with
      cannabis oil burns were younger (75% and 48% were younger than 41 years in the
      group with cannabis oil burns and the total burn group, respectively), were more
      likely to be male (83% in the group with cannabis oil burns v. 74% in the total
      burn group) and sustained burns over a larger percentage of their total body
      surface area (24% v. 9%). Patients with cannabis oil burns also required
      extensive surgical management (skin grafting in 75% of cases) and spent a
      substantial amount of time (mean 32 d) in the burn unit. INTERPRETATION: Burns
      from illegal cannabis oil manufacturing are large, require extensive management
      and involve younger patients than burns in general. Given that the frequency of
      cannabis oil burns may increase in Canada after legalization, Canadian burn
      centres are encouraged to monitor and report on cases with this injury mechanism.

PMID- 29362216
TI  - Perspectives on Incentive Spirometry Utility and Patient Protocols.
AB  - BACKGROUND: Incentive spirometry (IS) is widely used to prevent postoperative
      pulmonary complications, despite limited clinical effectiveness data and a lack
      of standardized use protocols. We sought to evaluate health care professionals'
      perspectives on IS effectiveness and use procedures. METHODS: An online survey
      was distributed via social media and newsletters to relevant national nursing and
      respiratory care societies. Attitudes concerning IS were compared between the
      American Association for Respiratory Care (AARC) and the nursing societies.
      RESULTS: A total of 1,681 responses (83.8% completion rate) were received. The
      clear majority of these respondents agreed that IS is essential to patient care
      (92.7%), improves pulmonary function (92.0%), improves inspiratory capacity
      (93.0%), helps to prevent (96.6%) and to reverse (90.0%) atelectasis, helps to
      prevent (92.5%) and to reverse (68.4%) pneumonia, and is as effective as early
      ambulation (74.0%), deep-breathing exercises (88.2%), and directed coughing
      (79.8%). Furthermore, most health care professionals believed that IS should be
      used routinely preoperatively (78.1%) and postoperatively (91.1%), used every
      hour (59.8%), used for an average of 9.6 (95% CI 9.3-9.9) breaths per session,
      used to achieve breath holds of 7.8 (95% CI 7.4-8.2) s, used to reach an initial
      target inspiratory volume of 1,288.5 (95% CI 1,253.8-1,323.2) mL, and used to
      achieve a daily inspiratory volume improvement of 525.6 (95% CI 489.8-561.4) mL.
      Of all respondents, 89.6% believed they received adequate IS education and
      training. Respondents from the AARC endorsed significantly less agreement
      relative to the nursing societies on most parameters for IS utility. CONCLUSIONS:
      There was a major discrepancy between health care professionals' beliefs and the
      published clinical effectiveness data supporting IS. Despite reported adequate
      education on IS, variability in what health care professionals believed to be
      appropriate use underscores the literature's lack of standardization and evidence
      for specific use procedures.

PMID- 29362218
TI  - Increasing Awareness of the Roles, Knowledge, and Skills of Respiratory
      Therapists Through an Interprofessional Education Experience.
AB  - BACKGROUND: The objectives of this study were: (1) to assess the use of
      interprofessional education (IPE) to improve the knowledge and skill levels of
      nursing and occupational therapy students regarding respiratory therapy (RT)
      medical devices and techniques, nursing and RT students regarding safe patient
      transfers, and RT and occupational therapy students regarding safe handling of a
      patient's medical lines during transfers and (2) to promote collaborative
      behaviors. METHODS: A prospective mixed methods approach was used for data
      collection of an IPE high-fidelity simulation experience involving 73 nursing,
      occupational therapy, and RT students at an academic medical institution. The
      Interprofessional Education Collaborative roles and responsibilities and
      interprofessional communication sub-competency guided the development of the IPE
      experience. RESULTS: The pre-post paired survey response rate was 82.2%.
      Significant increases in student perception of learning differed by profession.
      Student evaluations of the IPE experience suggested that IPE increased students'
      knowledge of the procedures performed by the other represented professions and
      that students were more likely to collaborate with these professions in the
      future. CONCLUSIONS: IPE improved student knowledge in the roles and
      responsibilities competency domain. In particular, nursing and occupational
      therapy students became more aware of the knowledge and skill set of the RT
      profession.

PMID- 29362217
TI  - Outcomes of Tracheostomized Subjects Undergoing Prolonged Mechanical Ventilation
      in an Intermediate-Care Facility.
AB  - BACKGROUND: The incidence of chronically ill subjects with prolonged mechanical
      ventilation (PMV) has significantly increased over the last decade because of
      improvements in acute critical care. The aim of this study was to describe the
      outcomes and care pathways of subjects receiving PMV through a tracheostomy tube
      in an intermediate-care facility. METHODS: Sixty-six subjects with chronic
      respiratory failure who experienced 109 hospitalizations between December 2010
      and December 2012 in a 34-bed post-care unit were retrospectively included and
      followed for at least 1 y. RESULTS: The median (interquartile range [IQR]) length
      of stay (LOS) was 42 (26-77) d. Subjects were admitted from home (40.4%), our
      hospital ICU (40.4%; median [IQR] LOS = 17 [7-38] d), or another hospital (19.2%;
      median [IQR] LOS = 60 [8-71] d, P = .001 vs LOS in ICU). Thirty-five percent of
      subjects were readmitted at least once during the follow-up period. Sixteen
      subjects died in the intermediate-care facility. Discharge destinations of alive
      subjects were home (n = 78), another hospital (n = 6), a skilled-nursing facility
      (n = 5), or an ICU (n = 4). A complete or partial weaning was obtained in 30.3%
      of subjects. One year after the first day of hospitalization, 57% of subjects
      were alive. CONCLUSIONS: Despite the chance of survival at 1 y and/or weaning
      from ventilation, the resources needed by subjects with PMV are high, as shown by
      the number of readmissions and long LOS in our unit and in other hospital units
      before transfer.

PMID- 29362219
TI  - Incentive Spirometry Adherence: A National Survey of Provider Perspectives.
AB  - BACKGROUND: Patient adherence is a critical factor for success of patient
      administered therapies, including incentive spirometry (IS). Patient adherence
      with IS is not known, so we sought to evaluate providers' perspectives on the
      current state of IS adherence and elucidate possible factors hindering patient
      adherence. METHODS: Respiratory therapists (RTs) and nurses across the United
      States were surveyed via social media and online newsletters. Surveys were
      distributed to the relevant national RT and nursing societies: the American
      Association for Respiratory Care, the Academy of Medical-Surgical Nurses, the
      American Society of Peri-Anesthesia Nurses, and the American Association of
      Critical-Care Nurses. RESULTS: Responses from 1,681 (83.8% completion rate) RTs
      and nurses were received. The clear majority of all providers agreed that patient
      adherence is poor (86.0%; 1,416 of 1,647 respondents) and should be improved
      (95.4%; 1,551 of 1,626 respondents). Providers believe that IS adherence is
      hindered by various factors. The most common reasons cited were that patients
      forget to use their ISs (83.5%; 1,404 of 1,681 respondents), do not use them
      effectively (74.4%; 1,251 of 1,681 respondents), and do not use them frequently
      enough (70.7%; 1,188 of 1,681 respondents). CONCLUSIONS: These findings from a
      large national survey of health care providers highlight the need for improved IS
      adherence and indicate that patient forgetfulness may be a large contributor to
      nonadherence. Efforts aimed at improving IS adherence are warranted.

PMID- 29362221
TI  - CCL20 Expression by Tumor-Associated Macrophages Predicts Progression of Human
      Primary Cutaneous Melanoma.
AB  - The chemokine axis CCR6/CCL20 is involved in cancer progression in a variety of
      tumors. Here, we show that CCR6 is expressed by melanoma cells. The CCR6 ligand,
      CCL20, induces migration and proliferation in vitro, and enhances tumor growth
      and metastasis in vivo Confocal analysis of melanoma tissues showed that CCR6 is
      expressed by tumor cells, whereas CCL20 is preferentially expressed by nontumoral
      cells in the stroma of certain tumors. Stromal CCL20, but not tumoral CCR6,
      predicted poor survival in a cohort of 40 primary melanoma patients. Tumor
      associated macrophages (TAM), independently of their M1/M2 polarization profile,
      were identified as the main source of CCL20 in primary melanomas that developed
      metastasis. In addition to CCL20, TAMs expressed TNF and VEGF-A protumoral
      cytokines, suggesting that melanoma progression is supported by macrophages with
      a differential activation state. Our data highlight the synergistic interaction
      between melanoma tumor cells and prometastatic macrophages through a CCR6/CCL20
      paracrine loop. Stromal levels of CCL20 in primary melanomas may be a clinically
      useful marker for assessing patient risk, making treatment decisions, and
      planning or analyzing clinical trials. Cancer Immunol Res; 1-9. (c)2018 AACR.

PMID- 29362222
TI  - NK Cells Control Tumor-Promoting Function of Neutrophils in Mice.
AB  - Although natural killer (NK) cells are recognized as direct antitumor effectors,
      the ability of NK cells to control cancer-associated inflammation, which
      facilitates tumor progression, remains unknown. In this study, we demonstrate
      that NK cells control tumor-promoting inflammation through functional
      modification of neutrophils. NK cells control the tumor-promoting function of
      neutrophils through an IFNgamma-dependent mechanism. Tumor progression in an NK
      cell-depleted host is diminished when the IL17A-neutrophil axis is absent. In NK
      cell-depleted mice, neutrophils acquire a tumor-promoting phenotype,
      characterized by upregulation of VEGF-A expression, which promotes tumor growth
      and angiogenesis. A VEGFR inhibitor which preferentially suppressed tumor growth
      in NK cell-depleted mice was dependent on neutrophils. Furthermore, the systemic
      neutropenia caused by an antimetabolite treatment showed an anticancer effect
      only in mice lacking NK cells. Thus, NK cells likely control the tumor-promoting
      and angiogenic function of neutrophils. Cancer Immunol Res; 6(3); 1-10. (c)2018
      AACR.

PMID- 29362220
TI  - Integration of Oncogenes via Sleeping Beauty as a Mouse Model of HPV16+ Oral
      Tumors and Immunologic Control.
AB  - Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer
      and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines
      are available, no effective therapeutic strategies to control active HPV diseases
      exist. Tumor implantation models are traditionally used to study HPV-associated
      buccal tumors. However, they fail to address precancerous phases of disease
      progression and display tumor microenvironments distinct from those observed in
      patients. Previously, K14-E6/E7 transgenic mouse models have been used to
      generate spontaneous tumors. However, the rate of tumor formation is
      inconsistent, and the host often develops immune tolerance to the viral
      oncoproteins. We developed a preclinical, spontaneous, HPV16+ buccal tumor model
      using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRas
      G12V , luciferase, and sleeping beauty (SB) transposase, followed by
      electroporation in the buccal mucosa. We evaluated responses to immunization with
      a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to
      distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRas G12V
      , luciferase, and SB transposase developed tumors within 3 weeks. We also found
      transient anti-CD3 administration is required to generate tumors in
      immunocompetent mice. Bioluminescence signals from luciferase correlated strongly
      with tumor growth, and tumors expressed HPV16-associated markers. We showed that
      pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor
      bearing mice. Lastly, we demonstrated that the generated tumor could migrate to
      tumor-draining lymph nodes. Our model provides an efficient method to induce
      spontaneous HPV+ tumor formation, which can be used to identify effective
      therapeutic interventions, analyze tumor migration, and conduct tumor biology
      research. Cancer Immunol Res; 6(3); 1-15. (c)2018 AACR.

PMID- 29362224
TI  - Correction: Quantifying exosome secretion from single cells reveals a modulatory
      role for GPCR signaling.

PMID- 29362223
TI  - A prion-like domain in Hsp42 drives chaperone-facilitated aggregation of
      misfolded proteins.
AB  - Chaperones with aggregase activity promote and organize the aggregation of
      misfolded proteins and their deposition at specific intracellular sites. This
      activity represents a novel cytoprotective strategy of protein quality control
      systems; however, little is known about its mechanism. In yeast, the small heat
      shock protein Hsp42 orchestrates the stress-induced sequestration of misfolded
      proteins into cytosolic aggregates (CytoQ). In this study, we show that Hsp42
      harbors a prion-like domain (PrLD) and a canonical intrinsically disordered
      domain (IDD) that act coordinately to promote and control protein aggregation.
      Hsp42 PrLD is essential for CytoQ formation and is bifunctional, mediating self
      association as well as binding to misfolded proteins. Hsp42 IDD confines
      chaperone and aggregase activity and affects CytoQ numbers and stability in vivo.
      Hsp42 PrLD and IDD are both crucial for cellular fitness during heat stress,
      demonstrating the need for sequestering misfolded proteins in a regulated manner.

PMID- 29362225
TI  - The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling.
AB  - The mitotic spindle checkpoint delays anaphase onset in the presence of
      unattached kinetochores, and efficient checkpoint signaling requires kinetochore
      localization of the Rod-ZW10-Zwilch (RZZ) complex. In the present study, we show
      that human Chmp4c, a protein involved in membrane remodeling, localizes to
      kinetochores in prometaphase but is reduced in chromosomes aligned at the
      metaphase plate. Chmp4c promotes stable kinetochore-microtubule attachments and
      is required for proper mitotic progression, faithful chromosome alignment, and
      segregation. Depletion of Chmp4c diminishes localization of RZZ and Mad1-Mad2
      checkpoint proteins to prometaphase kinetochores and impairs mitotic arrest when
      microtubules are depolymerized by nocodazole. Furthermore, Chmp4c binds to ZW10
      through a small C-terminal region, and constitutive Chmp4c kinetochore targeting
      causes a ZW10-dependent checkpoint metaphase arrest. In addition, Chmp4c spindle
      functions do not require endosomal sorting complex required for transport
      dependent membrane remodeling. These results show that Chmp4c regulates the
      mitotic spindle checkpoint by promoting localization of the RZZ complex to
      unattached kinetochores.

PMID- 29362226
TI  - ELOVL4-Mediated Production of Very Long-Chain Ceramides Stabilizes Tight
      Junctions and Prevents Diabetes-Induced Retinal Vascular Permeability.
AB  - Tight junctions (TJs) involve close apposition of transmembrane proteins between
      cells. Although TJ proteins have been studied in detail, the role of lipids is
      largely unknown. We addressed the role of very long-chain (VLC >=26) ceramides in
      TJs using diabetes-induced loss of the blood-retinal barrier as a model. VLC
      fatty acids that incorporate into VLC ceramides are produced by elongase
      elongation of very long-chain fatty acids protein 4 (ELOVL4). ELOVL4 is
      significantly reduced in the diabetic retina. Overexpression of ELOVL4
      significantly decreased basal permeability, inhibited vascular endothelial growth
      factor (VEGF)- and interleukin-1beta-induced permeability, and prevented VEGF
      induced decrease in occludin expression and border staining of TJ proteins ZO-1
      and claudin-5. Intravitreal delivery of AAV2-hELOVL4 reduced diabetes-induced
      increase in vascular permeability. Ultrastructure and lipidomic analysis revealed
      that omega-linked acyl-VLC ceramides colocalize with TJ complexes. Overall,
      normalization of retinal ELOVL4 expression could prevent blood-retinal barrier
      dysregulation in diabetic retinopathy through an increase in VLC ceramides and
      stabilization of TJs.

PMID- 29362227
TI  - Down Syndrome Critical Region 1 Gene, Rcan1, Helps Maintain a More Fused
      Mitochondrial Network.
AB  - RATIONALE: The regulator of calcineurin 1 (RCAN1) inhibits CN (calcineurin), a
      Ca2+-activated protein phosphatase important in cardiac remodeling. In humans,
      RCAN1 is located on chromosome 21 in proximity to the Down syndrome critical
      region. The hearts and brains of Rcan1 KO mice are more susceptible to damage
      from ischemia/reperfusion (I/R); however, the underlying cause is not known.
      OBJECTIVE: Mitochondria are key mediators of I/R damage. The goal of these
      studies was to determine the impact of RCAN1 on mitochondrial dynamics and
      function. METHODS AND RESULTS: Using both neonatal and isolated adult
      cardiomyocytes, we show that, when RCAN1 is depleted, the mitochondrial network
      is more fragmented because of increased CN-dependent activation of the fission
      protein, DRP1 (dynamin-1-like). Mitochondria in RCAN1-depleted cardiomyocytes
      have reduced membrane potential, O2 consumption, and generation of reactive
      oxygen species, as well as a reduced capacity for mitochondrial Ca2+ uptake.
      RCAN1-depleted cardiomyocytes were more sensitive to I/R; however,
      pharmacological inhibition of CN, DRP1, or CAPN (calpains; Ca2+-activated
      proteases) restored protection, suggesting that in the absence of RCAN1, CAPN
      mediated damage after I/R is greater because of a decrease in the capacity of
      mitochondria to buffer cytoplasmic Ca2+. Increasing RCAN1 levels by adenoviral
      infection was sufficient to enhance fusion and confer protection from I/R. To
      examine the impact of more modest, and biologically relevant, increases in RCAN1,
      we compared the mitochondrial network in induced pluripotent stem cells derived
      from individuals with Down syndrome to that of isogenic, disomic controls.
      Mitochondria were more fused, and O2 consumption was greater in the trisomic
      induced pluripotent stem cells; however, coupling efficiency and metabolic
      flexibility were compromised compared with disomic induced pluripotent stem
      cells. Depletion of RCAN1 from trisomic induced pluripotent stem cells was
      sufficient to normalize mitochondrial dynamics and function. CONCLUSIONS: RCAN1
      helps maintain a more interconnected mitochondrial network, and maintaining
      appropriate RCAN1 levels is important to human health and disease.

PMID- 29362228
TI  - Maternal exposure to UV filters: associations with maternal thyroid hormones, IGF
      I/IGFBP3 and birth outcomes.
AB  - BACKGROUND: Several chemical UV filters/absorbers ('UV filters' hereafter) have
      endocrine-disrupting properties in vitro and in vivo. Exposure to these
      chemicals, especially during prenatal development, is of concern. OBJECTIVES: To
      examine maternal exposure to UV filters, associations with maternal thyroid
      hormone, with growth factor concentrations as well as to birth outcomes. METHODS:
      Prospective study of 183 pregnant women with 2nd trimester serum and urine
      samples available. Maternal concentrations of the chemical UV filters
      benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy
      benzophenone (4-HBP) in serum were measured by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The relationships between 2nd trimester maternal
      concentrations of the three chemical UV filters and maternal serum concentrations
      of thyroid hormones and growth factors, as well as birth outcomes (weight,
      height, and head and abdominal circumferences) were examined. RESULTS: Positive
      associations between maternal serum concentrations of 4-HBP and triiodothyronine
      (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding
      protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of
      mothers in the middle 4-HBP exposure group had statistically significantly lower
      weight and shorter head and abdominal circumferences at birth compared to the low
      exposure group. CONCLUSIONS: Widespread exposure of pregnant women to chemical UV
      filters and the possible impact on maternal thyroid hormones and growth factors,
      and on fetal growth, calls for further studies on possible long-term consequences
      of the exposure to UV filters on fetal development and children's health.

PMID- 29362229
TI  - Mycoplasma pneumoniae Community-Acquired Respiratory Distress Syndrome Toxin Uses
      a Novel KELED Sequence for Retrograde Transport and Subsequent Cytotoxicity.
AB  - Mycoplasma pneumoniae is an atypical bacterium that causes respiratory illnesses
      in humans, including pharyngitis, tracheobronchitis, and community-acquired
      pneumonia (CAP). It has also been directly linked to reactive airway disease,
      asthma, and extrapulmonary pathologies. During its colonization, M. pneumoniae
      expresses a unique ADP-ribosylating and vacuolating cytotoxin designated
      community-acquired respiratory distress syndrome (CARDS) toxin. CARDS toxin
      persists and localizes in the airway in CAP patients, asthmatics, and trauma
      patients with ventilator-associated pneumonia. Although CARDS toxin binds to
      specific cellular receptors, is internalized, and induces hyperinflammation,
      histopathology, mucus hyperplasia, and other airway injury, the intracellular
      trafficking of CARDS toxin remains unclear. Here, we show that CARDS toxin
      translocates through early and late endosomes and the Golgi complex and
      concentrates at the perinuclear region to reach the endoplasmic reticulum (ER).
      Using ER-targeted SNAP-tag, we confirmed the association of CARDS toxin with the
      ER and determined that CARDS toxin follows the retrograde pathway. In addition,
      we identified a novel CARDS toxin amino acid fingerprint, KELED, that is required
      for toxin transport to the ER and subsequent toxin-mediated
      cytotoxicity.IMPORTANCEMycoplasma pneumoniae, a leading cause of bacterial
      community-acquired pneumonia (CAP) among children and adults in the United
      States, synthesizes a 591-amino-acid ADP-ribosylating and vacuolating protein,
      designated community-acquired respiratory distress syndrome (CARDS) toxin. CARDS
      toxin alone is sufficient to induce and mimic major inflammatory and
      histopathological phenotypes associated with M. pneumoniae infection in rodents
      and primates. In order to elicit its ADP-ribosylating and vacuolating activities,
      CARDS toxin must bind to host cell receptors, be internalized via clathrin
      mediated pathways, and subsequently be transported to specific intracellular
      organelles. Here, we demonstrate how CARDS toxin utilizes its unique KELED
      sequence to exploit the retrograde pathway machinery to reach the endoplasmic
      reticulum (ER) and fulfill its cytopathic potential. The knowledge generated from
      these studies may provide important clues to understand the mode of action of
      CARDS toxin and develop interventions that reduce or eliminate M. pneumoniae
      associated airway and extrapulmonary pathologies.

PMID- 29362230
TI  - Contrasting Function of Structured N-Terminal and Unstructured C-Terminal
      Segments of Mycobacterium tuberculosis PPE37 Protein.
AB  - Pathogens frequently employ eukaryotic linear motif (ELM)-rich intrinsically
      disordered proteins (IDPs) to perturb and hijack host cell networks for a
      productive infection. Mycobacterium tuberculosis has a relatively high percentage
      of IDPs in its proteome, the significance of which is not known. The
      Mycobacterium-specific PE-PPE protein family has several members with unusually
      high levels of structural disorder and disorder-promoting Ala/Gly residues. PPE37
      protein, a member of this family, carries an N-terminal PPE domain capable of
      iron binding, two transmembrane domains, and a disordered C-terminal segment
      harboring ELMs and a eukaryotic nuclear localization signal (NLS). PPE37,
      expressed as a function of low iron stress, was cleaved by M. tuberculosis
      protease into N- and C-terminal segments. A recombinant N-terminal segment (P37N)
      caused proliferation and differentiation of monocytic THP-1 cells, into CD11c, DC
      SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing
      nonintegrin)-positive semimature dendritic cells exhibiting high interleukin-10
      (IL-10) but negligible IL-12 and also low tumor necrosis factor alpha (TNF-alpha)
      secretion-an environment suitable for maintaining tolerogenic immune cells. The C
      terminal segment entered the macrophage nucleus and induced caspase-3-dependent
      apoptosis of host cells. Mice immunized with recombinant PPE37FL and PPE37N
      evoked strong anti-inflammatory response, validating the in vitro
      immunostimulatory effect. Analysis of the IgG response of PPE37FL and PPE37N
      revealed significant immunoreactivities in different categories of TB patients,
      viz. pulmonary TB (PTB) and extrapulmonary TB (EPTB), vis-a-vis healthy controls.
      These results support the role of IDPs in performing contrasting activities to
      modulate the host processes, possibly through molecular mimicry and cross talk in
      two spatially distinct host environments which may likely aid M. tuberculosis
      survival and pathogenesis.IMPORTANCE To hijack the human host cell machinery to
      enable survival inside macrophages, the pathogen Mycobacterium tuberculosis
      requires a repertoire of proteins that can mimic host protein function and
      modulate host cell machinery. Here, we have shown how a single protein can play
      multiple functions and hijack the host cell for the benefit of the pathogen. Full
      length membrane-anchored PPE37 protein is cleaved into N- and C-terminal domains
      under iron-depleted conditions. The N-terminal domain facilitates the propathogen
      semimature tolerogenic state of dendritic cells, whereas the C-terminal segment
      is localized into host cell nucleus and induces apoptosis. The immune
      implications of these in vitro observations were assessed and validated in mice
      and also human TB patients. This study presents novel mechanistic insight adopted
      by M. tuberculosis to survive inside host cells.

PMID- 29362232
TI  - Stress-Induced Reorganization of the Mycobacterial Membrane Domain.
AB  - Cell elongation occurs primarily at the mycobacterial cell poles, but the
      molecular mechanisms governing this spatial regulation remain elusive. We
      recently reported the presence of an intracellular membrane domain (IMD) that was
      spatially segregated from the conventional plasma membrane in Mycobacterium
      smegmatis The IMD is enriched in the polar region of actively elongating cells
      and houses many essential enzymes involved in envelope biosynthesis, suggesting
      its role in spatially restricted elongation at the cell poles. Here, we examined
      reorganization of the IMD when the cells are no longer elongating. To monitor the
      IMD, we used a previously established reporter strain expressing fluorescent IMD
      markers and grew it to the stationary growth phase or exposed the cells to
      nutrient starvation. In both cases, the IMD was delocalized from the cell pole
      and distributed along the sidewall. Importantly, the IMD could still be isolated
      biochemically by density gradient fractionation, indicating its maintenance as a
      membrane domain. Chemical and genetic inhibition of peptidoglycan biosynthesis
      led to the delocalization of the IMD, suggesting the suppression of peptidoglycan
      biosynthesis as a trigger of spatial IMD rearrangement. Starved cells with a
      delocalized IMD can resume growth upon nutrient repletion, and polar enrichment
      of the IMD coincides with the initiation of cell elongation. These data reveal
      that the IMD is a membrane domain with the unprecedented capability of
      subcellular repositioning in response to the physiological conditions of the
      mycobacterial cell.IMPORTANCE Mycobacteria include medically important species,
      such as the human tuberculosis pathogen Mycobacterium tuberculosis The highly
      impermeable cell envelope is a hallmark of these microbes, and its biosynthesis
      is a proven chemotherapeutic target. Despite the accumulating knowledge regarding
      the biosynthesis of individual envelope components, the regulatory mechanisms
      behind the coordinated synthesis of the complex cell envelope remain elusive. We
      previously reported the presence of a metabolically active membrane domain
      enriched in the elongating poles of actively growing mycobacteria. However, the
      spatiotemporal dynamics of the membrane domain in response to stress have not
      been examined. Here, we show that the membrane domain is spatially reorganized
      when growth is inhibited in the stationary growth phase, under nutrient
      starvation, or in response to perturbation of peptidoglycan biosynthesis. Our
      results suggest that mycobacteria have a mechanism to spatiotemporally coordinate
      the membrane domain in response to metabolic needs under different growth
      conditions.

PMID- 29362231
TI  - Complement C5a Receptor 1 Exacerbates the Pathophysiology of N. meningitidis
      Sepsis and Is a Potential Target for Disease Treatment.
AB  - Sepsis caused by Neisseria meningitidis (meningococcus) is a rapidly progressing,
      life-threatening disease. Because its initial symptoms are rather unspecific,
      medical attention is often sought too late, i.e., when the systemic inflammatory
      response is already unleashed. This in turn limits the success of antibiotic
      treatment. The complement system is generally accepted as the most important
      innate immune determinant against invasive meningococcal disease since it
      protects the host through the bactericidal membrane attack complex. However,
      complement activation concomitantly liberates the C5a peptide, and it remains
      unclear whether this potent anaphylatoxin contributes to protection and/or drives
      the rapidly progressing immunopathogenesis associated with meningococcal disease.
      Here, we dissected the specific contribution of C5a receptor 1 (C5aR1), the
      canonical receptor for C5a, using a mouse model of meningococcal sepsis. Mice
      lacking C3 or C5 displayed susceptibility that was enhanced by >1,000-fold or 100
      fold, respectively, consistent with the contribution of these components to
      protection. In clear contrast, C5ar1-/- mice resisted invasive meningococcal
      infection and cleared N. meningitidis more rapidly than wild-type (WT) animals.
      This favorable outcome stemmed from an ameliorated inflammatory cytokine response
      to N. meningitidis in C5ar1-/- mice in both in vivo and ex vivo whole-blood
      infections. In addition, inhibition of C5aR1 signaling without interference with
      the complement bactericidal activity reduced the inflammatory response also in
      human whole blood. Enticingly, pharmacologic C5aR1 blockade enhanced mouse
      survival and lowered meningococcal burden even when the treatment was
      administered after sepsis induction. Together, our findings demonstrate that
      C5aR1 drives the pathophysiology associated with meningococcal sepsis and
      provides a promising target for adjunctive therapy.IMPORTANCE The devastating
      consequences of N. meningitidis sepsis arise due to the rapidly arising and self
      propagating inflammatory response that mobilizes antibacterial defenses but also
      drives the immunopathology associated with meningococcemia. The complement
      cascade provides innate broad-spectrum protection against infection by directly
      damaging the envelope of pathogenic microbes through the membrane attack complex
      and triggers an inflammatory response via the C5a peptide and its receptor C5aR1
      aimed at mobilizing cellular effectors of immunity. Here, we consider the
      potential of separating the bactericidal activities of the complement cascade
      from its immune activating function to improve outcome of N. meningitidis sepsis.
      Our findings demonstrate that the specific genetic or pharmacological disruption
      of C5aR1 rapidly ameliorates disease by suppressing the pathogenic inflammatory
      response and, surprisingly, allows faster clearance of the bacterial infection.
      This outcome provides a clear demonstration of the therapeutic benefit of the use
      of C5aR1-specific inhibitors to improve the outcome of invasive meningococcal
      disease.

PMID- 29362233
TI  - Genomic Analyses Reveal the Common Occurrence and Complexity of Plasmodium vivax
      Relapses in Cambodia.
AB  - Plasmodium vivax parasites have a unique dormant stage that can cause relapses
      weeks or months after the initial infection. These dormant parasites are among
      the main challenges of vivax malaria control as they constitute a reservoir that
      is difficult to eliminate. Since field studies are confounded by reinfections and
      possible recrudescence of drug-resistant parasites, most analyses of P. vivax
      relapses have focused on travelers returning from regions of malaria endemicity.
      However, it is not clear whether these individuals accurately recapitulate the
      relapse patterns of repeatedly infected individuals residing in areas of
      endemicity. Here, we present analyses of vivax malaria patients enrolled in a
      tightly controlled field study in Cambodia. After antimalarial drug treatment was
      administered, we relocated 20 individuals to a nontransmission area and followed
      them for 60 days, with blood collection performed every second day. Our analyses
      reveal that 60% of the patients relapsed during the monitoring period. Using
      whole-genome sequencing and high-throughput genotyping, we showed that relapses
      in Cambodia are often polyclonal and that the relapsing parasites harbor various
      degrees of relatedness to the parasites present in the initial infection. Our
      analyses also showed that clone populations differed dynamically, with new clones
      emerging during the course of the relapsing infections. Overall, our study data
      show that it is possible to investigate the patterns, dynamics, and diversity of
      P. vivax relapses of individuals living in a region of malaria endemicity and
      reveal that P. vivax relapses are much more pervasive and complex than previously
      considered. (This study has been registered at ClinicalTrials.gov under
      registration no. NCT02118090)IMPORTANCEP. vivax parasites can remain dormant in
      the liver and relapse weeks or months after the initial infection, greatly
      complicating malaria control and elimination efforts. The few investigations of
      this dormant stage have relied on travelers and military personnel returning from
      areas of malaria endemicity. However, it is not clear whether these individuals,
      exposed to a limited number of infections, accurately represent the patterns of
      relapses of individuals living in areas of endemicity, who are repeatedly
      infected by P. vivax parasites. Our study combined tightly controlled fieldwork
      with comprehensive genomic analyses, and our report provides a first opportunity
      to investigate the patterns, dynamics, and diversity of P. vivax relapses
      directly with individuals living in areas of endemicity.

PMID- 29362234
TI  - Are Phage Lytic Proteins the Secret Weapon To Kill Staphylococcus aureus?
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most threatening
      microorganisms for global human health. The current strategies to reduce the
      impact of S. aureus include a restrictive control of worldwide antibiotic use,
      prophylactic measures to hinder contamination, and the search for novel
      antimicrobials to treat human and animal infections caused by this bacterium. The
      last strategy is currently the focus of considerable research. In this regard,
      phage lytic proteins (endolysins and virion-associated peptidoglycan hydrolases
      [VAPGHs]) have been proposed as suitable candidates. Indeed, these proteins
      display narrow-spectrum antimicrobial activity and a virtual lack of bacterial
      resistance development. Additionally, the therapeutic use of phage lytic proteins
      in S. aureus animal infection models is yielding promising results, showing good
      efficacy without apparent side effects. Nonetheless, human clinical trials are
      still in progress, and data are not available yet. This minireview also analyzes
      the main obstacles for introducing phage lytic proteins as human therapeutics
      against S. aureus infections. Besides the common technological problems derived
      from large-scale production of therapeutic proteins, a major setback is the lack
      of a proper legal framework regulating their use. In that sense, the relevant
      health authorities should urgently have a timely discussion about these new
      antimicrobials. On the other hand, the research community should provide data to
      dispel any doubts regarding their efficacy and safety. Overall, the appropriate
      scientific data and regulatory framework will encourage pharmaceutical companies
      to invest in these promising antimicrobials.

PMID- 29362236
TI  - A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion
      System in Host.
AB  - Most pathogenic bacteria deliver virulence factors into host cytosol through type
      III secretion systems (T3SS) to perturb host immune responses. The expression of
      T3SS is often repressed in rich medium but is specifically induced in the host
      environment. The molecular mechanisms underlying host-specific induction of T3SS
      expression is not completely understood. Here we demonstrate in Xanthomonas citri
      that host-induced phosphorylation of the ATP-dependent protease Lon stabilizes
      HrpG, the master regulator of T3SS, conferring bacterial virulence. Ser/Thr/Tyr
      phosphoproteome analysis revealed that phosphorylation of Lon at serine 654
      occurs in the citrus host. In rich medium, Lon represses T3SS by degradation of
      HrpG via recognition of its N terminus. Genetic and biochemical data indicate
      that phosphorylation at serine 654 deactivates Lon proteolytic activity and
      attenuates HrpG proteolysis. Substitution of alanine for Lon serine 654 resulted
      in repression of T3SS gene expression in the citrus host through robust
      degradation of HrpG and reduced bacterial virulence. Our work reveals a novel
      mechanism for distinct regulation of bacterial T3SS in different environments.
      Additionally, our data provide new insight into the role of protein
      posttranslational modification in the regulation of bacterial
      virulence.IMPORTANCE Type III secretion systems (T3SS) are an essential virulence
      trait of many bacterial pathogens because of their indispensable role in the
      delivery of virulence factors. However, expression of T3SS in the noninfection
      stage is energy consuming. Here, we established a model to explain the
      differential regulation of T3SS in host and nonhost environments. When
      Xanthomonas cells are grown in rich medium, the T3SS regulator HrpG is targeted
      by Lon protease for proteolysis. The degradation of HrpG leads to downregulated
      expression of HrpX and the hrp/hrc genes. When Xanthomonas cells infect the host,
      specific plant stimuli can be perceived and induce Lon phosphorylation at serine
      654. Phosphorylation on Lon attenuates its proteolytic activity and protects HrpG
      from degradation. Consequently, enhanced stability of HrpG activates HrpX and
      turns on bacterial T3SS in the host. Our work provides a novel molecular
      mechanism underlying host-dependent activation of bacterial T3SS.

PMID- 29362235
TI  - The Ancient Link between G-Protein-Coupled Receptors and C-Terminal Phospholipid
      Kinase Domains.
AB  - Sensing external signals and transducing these into intracellular responses
      requires a molecular signaling system that is crucial for every living organism.
      Two important eukaryotic signal transduction pathways that are often interlinked
      are G-protein signaling and phospholipid signaling. Heterotrimeric G-protein
      subunits activated by G-protein-coupled receptors (GPCRs) are typical stimulators
      of phospholipid signaling enzymes such as phosphatidylinositol phosphate kinases
      (PIPKs) or phospholipase C (PLC). However, a direct connection between the two
      pathways likely exists in oomycetes and slime molds, as they possess a unique
      class of GPCRs that have a PIPK as an accessory domain. In principle, these so
      called GPCR-PIPKs have the capacity of perceiving an external signal (via the
      GPCR domain) that, via PIPK, directly activates downstream phospholipid
      signaling. Here we reveal the sporadic occurrence of GPCR-PIPKs in all eukaryotic
      supergroups, except for plants. Notably, all species having GPCR-PIPKs are
      unicellular microorganisms that favor aquatic environments. Phylogenetic analysis
      revealed that GPCR-PIPKs are likely ancestral to eukaryotes and significantly
      expanded in the last common ancestor of oomycetes. In addition to GPCR-PIPKs, we
      identified five hitherto-unknown classes of GPCRs with accessory domains, four of
      which are universal players in signal transduction. Similarly to GPCR-PIPKs, this
      enables a direct coupling between extracellular sensing and downstream signaling.
      Overall, our findings point to an ancestral signaling system in eukaryotes where
      GPCR-mediated sensing is directly linked to downstream responses.IMPORTANCE G
      protein-coupled receptors (GPCRs) are central sensors that activate eukaryotic
      signaling and are the primary targets of human drugs. In this report, we provide
      evidence for the widespread though limited presence of a novel class of GPCRs in
      a variety of unicellular eukaryotes. These include free-living organisms and
      organisms that are pathogenic for plants, animals, and humans. The novel GPCRs
      have a C-terminal phospholipid kinase domain, pointing to a direct link between
      sensing external signals via GPCRs and downstream intracellular phospholipid
      signaling. Genes encoding these receptors were likely present in the last common
      eukaryotic ancestor and were lost during the evolution of higher eukaryotes. We
      further describe five other types of GPCRs with a catalytic accessory domain, the
      so-called GPCR-bigrams, four of which may potentially have a role in signaling.
      These findings shed new light onto signal transduction in microorganisms and
      provide evidence for alternative eukaryotic signaling pathways.

PMID- 29362237
TI  - Processing of Candida albicans Ece1p Is Critical for Candidalysin Maturation and
      Fungal Virulence.
AB  - Candida albicans is an opportunistic fungal pathogen responsible for superficial
      and life-threatening infections in humans. During mucosal infection, C. albicans
      undergoes a morphological transition from yeast to invasive filamentous hyphae
      that secrete candidalysin, a 31-amino-acid peptide toxin required for virulence.
      Candidalysin damages epithelial cell plasma membranes and stimulates the
      activating protein 1 (AP-1) transcription factor c-Fos (via p38-mitogen-activated
      protein kinase [MAPK]), and the MAPK phosphatase MKP1 (via extracellular signal
      regulated kinases 1 and 2 [ERK1/2]-MAPK), which trigger and regulate
      proinflammatory cytokine responses, respectively. The candidalysin toxin resides
      as a discrete cryptic sequence within a larger 271-amino-acid parental
      preproprotein, Ece1p. Here, we demonstrate that kexin-like proteinases, but not
      secreted aspartyl proteinases, initiate a two-step posttranslational processing
      of Ece1p to produce candidalysin. Kex2p-mediated proteolysis of Ece1p after Arg61
      and Arg93, but not after other processing sites within Ece1p, is required to
      generate immature candidalysin from Ece1p, followed by Kex1p-mediated removal of
      a carboxyl arginine residue to generate mature candidalysin. C. albicans strains
      harboring mutations of Arg61 and/or Arg93 did not secrete candidalysin, were
      unable to induce epithelial damage and inflammatory responses in vitro, and
      showed attenuated virulence in vivo in a murine model of oropharyngeal
      candidiasis. These observations identify enzymatic processing of C. albicans
      Ece1p by kexin-like proteinases as crucial steps required for candidalysin
      production and fungal pathogenicity.IMPORTANCECandida albicans is an
      opportunistic fungal pathogen that causes mucosal infection in millions of
      individuals worldwide. Successful infection requires the secretion of
      candidalysin, the first cytolytic peptide toxin identified in any human fungal
      pathogen. Candidalysin is derived from its parent protein Ece1p. Here, we
      identify two key amino acids within Ece1p vital for processing and production of
      candidalysin. Mutations of these residues render C. albicans incapable of causing
      epithelial damage and markedly reduce mucosal infection in vivo Importantly,
      candidalysin production requires two individual enzymatic events. The first
      involves processing of Ece1p by Kex2p, yielding immature candidalysin, which is
      then further processed by Kex1p to produce the mature toxin. These observations
      identify important steps for C. albicans pathogenicity at mucosal surfaces.

PMID- 29362238
TI  - Adaptive Evolution of RH5 in Ape Plasmodium species of the Laverania Subgenus.
AB  - Plasmodium falciparum, the major cause of malaria morbidity and mortality in
      humans, has been shown to have emerged after cross-species transmission of one of
      six host-specific parasites (subgenus Laverania) infecting wild chimpanzees (Pan
      troglodytes) and western gorillas (Gorilla gorilla). Binding of the parasite
      encoded ligand RH5 to the host protein basigin is essential for erythrocyte
      invasion and has been implicated in host specificity. A recent study claimed to
      have found two amino acid changes in RH5 that "drove the host shift leading to
      the emergence of P. falciparum as a human pathogen." However, the ape Laverania
      data available at that time, which included only a single distantly related
      chimpanzee parasite sequence, were inadequate to justify any such conclusion.
      Here, we have investigated Laverania Rh5 gene evolution using sequences from all
      six ape parasite species. Searching for gene-wide episodic selection across the
      entire Laverania phylogeny, we found eight codons to be under positive selection,
      including three that correspond to contact residues known to form hydrogen bonds
      between P. falciparum RH5 and human basigin. One of these sites (residue 197) has
      changed subsequent to the transmission from apes to humans that gave rise to P.
      falciparum, suggesting a possible role in the adaptation of the gorilla parasite
      to the human host. We also found evidence that the patterns of nucleotide
      polymorphisms in P. falciparum are not typical of Laverania species and likely
      reflect the recent demographic history of the human parasite.IMPORTANCE A number
      of closely related, host-specific malaria parasites infecting wild chimpanzees
      and gorillas have recently been described. The most important cause of human
      malaria, Plasmodium falciparum, is now known to have resulted from a cross
      species transmission of one of the gorilla parasites. Overcoming species-specific
      interactions between a parasite ligand, RH5, and its receptor on host cells,
      basigin, was likely an important step in the origin of the human parasite. We
      have investigated the evolution of the Rh5 gene and found evidence of adaptive
      changes during the diversification of the ape parasite species at sites that are
      known to form bonds with human basigin. One of these changes occurred at the
      origin of P. falciparum, implicating it as an important adaptation to the human
      host.

PMID- 29362239
TI  - Staphylococcus aureus Responds to the Central Metabolite Pyruvate To Regulate
      Virulence.
AB  - Staphylococcus aureus is a versatile bacterial pathogen that can cause
      significant disease burden and mortality. Like other pathogens, S. aureus must
      adapt to its environment to produce virulence factors to survive the immune
      responses evoked by infection. Despite the importance of environmental signals
      for S. aureus pathogenicity, only a limited number of these signals have been
      investigated in detail for their ability to modulate virulence. Here we show that
      pyruvate, a central metabolite, causes alterations in the overall metabolic flux
      of S. aureus and enhances its pathogenicity. We demonstrate that pyruvate induces
      the production of virulence factors such as the pore-forming leucocidins and that
      this induction results in increased virulence of community-acquired methicillin
      resistant S. aureus (CA-MRSA) clone USA300. Specifically, we show that an
      efficient "pyruvate response" requires the activation of S. aureus master
      regulators AgrAC and SaeRS as well as the ArlRS two-component system. Altogether,
      our report further establishes a strong relationship between metabolism and
      virulence and identifies pyruvate as a novel regulatory signal for the
      coordination of the S. aureus virulon through intricate regulatory
      networks.IMPORTANCE Delineation of the influence of host-derived small molecules
      on the makeup of human pathogens is a growing field in understanding host
      pathogen interactions. S. aureus is a prominent pathogen that colonizes up to one
      third of the human population and can cause serious infections that result in
      mortality in ~15% of cases. Here, we show that pyruvate, a key nutrient and
      central metabolite, causes global changes to the metabolic flux of S. aureus and
      activates regulatory networks that allow significant increases in the production
      of leucocidins. These and other virulence factors are critical for S. aureus to
      infect diverse host niches, initiate infections, and effectively subvert host
      immune responses. Understanding how environmental signals, particularly ones that
      are essential to and prominent in the human host, affect virulence will allow us
      to better understand pathogenicity and consider more-targeted approaches to
      tackling the current S. aureus epidemic.

PMID- 29362240
TI  - Evaluation of Preexisting Anti-Hemagglutinin Stalk Antibody as a Correlate of
      Protection in a Healthy Volunteer Challenge with Influenza A/H1N1pdm Virus.
AB  - Influenza virus hemagglutinin (HA) surface glycoprotein is currently the primary
      target of licensed influenza vaccines. Recently, broadly reactive antibodies that
      target the stalk region of the HA have become a major focus of current novel
      vaccine development. These antibodies have been observed in humans after natural
      infection with influenza A virus, but the data are limited. Using samples and
      data from the uniquely controlled setting of an influenza A/H1N1 virus human
      challenge study of healthy volunteers, we performed a secondary analysis that for
      the first time explores the role of anti-HA stalk antibody as a human correlate
      of protection. An anti-HA stalk antibody enzyme-linked immunosorbent assay
      (ELISA) was performed on samples from 65 participants challenged with a 2009
      H1N1pdm virus. Pre- and postchallenge anti-HA stalk titers were then correlated
      with multiple outcome measures to evaluate anti-HA stalk antibody titer as a
      correlate of protection. Anti-HA stalk antibody titers were present before
      challenge and rose in response to challenge in 64% of individuals. Those
      individuals with higher titers at baseline were less likely to develop shedding,
      but not less likely to develop symptoms. Similar to the hemagglutination
      inhibition (HAI) titer, the baseline anti-HA stalk antibody titer did not
      independently predict a decrease in the severity of influenza disease, while the
      antineuraminidase (neuraminidase inhibition [NAI]) titer did. As a correlate of
      protection, the naturally occurring anti-HA stalk antibody titer is predictive of
      a reduction of certain aspects of disease similar to HAI titer, but the NAI titer
      is the only identified correlate that is an independent predictor of a reduction
      of all assessed influenza clinical outcome measures.IMPORTANCE This is the first
      study to evaluate preexisting anti-HA stalk antibodies as a predictor of
      protection. We use a healthy volunteer influenza challenge trial for an
      examination of the role such antibodies play in protection. This study
      demonstrates that anti-HA stalk antibodies are naturally generated in response to
      an infection, but there is significant variability in response. Similar to
      antibodies that target the HA head, baseline anti-HA stalk antibody titer is a
      correlate of protection in terms of reduced shedding, but it is not a predictor
      of reduced clinical disease or an independent predictor of disease severity.
      These results, in the context of the limited data available in humans, suggest
      that vaccines that induce anti-HA stalk antibodies could play a role in future
      vaccine strategies, but alone, this target may be insufficient to induce a fully
      protective vaccine and overcome some of the issues identified with current
      vaccines.

PMID- 29362241
TI  - Barriers and facilitators to medication adherence: a qualitative study with
      general practitioners.
AB  - BACKGROUND: General practitioners (GPs) manage the drug therapies of people with
      chronic diseases, and poor adherence to medication remains a major challenge.
      OBJECTIVE: This qualitative study examined GPs' insights into non-adherence and
      ways of overcoming this problem. METHODS: We ran four focus groups comprising 16
      GPs at the Kirkkonummi Health Centre (Southern Finland). Interviews were
      audiotaped, transcribed verbatim and analysed by inductive content analysis. MAIN
      RESULTS: The two main themes in the discussions with the GPs were non-adherence
      in the care of chronic disease and increased need for medicine information. The
      medication management challenges identified were related to: patient-specific
      factors, the healthcare system, characteristics of drug therapies and the
      function and role of healthcare professionals as a team. To improve the
      situation, the GPs offered a number of solutions: improved coordination of care,
      better patient education and IT systems as well as enhanced interprofessional
      involvement in the follow-up of patients. DISCUSSION AND CONCLUSIONS: With an
      ageing population, the GPs were increasingly confronted with non-adherence in the
      care of chronic diseases. They had mostly a positive attitude towards organising
      care in a more interprofessional manner. To support medication adherence and self
      management, the GPs appreciated pharmacists' assistance especially with patients
      with polypharmacy and chronic diseases.

PMID- 29362242
TI  - Two alternatives versus the standard Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) summary of findings (SoF) tables to improve
      understanding in the presentation of systematic review results: a three-arm,
      randomised, controlled, non-inferiority trial.
AB  - OBJECTIVE: Summary of findings (SoF) tables present results of systematic reviews
      in a concise and explicit format. Adopted by many review groups including the
      Cochrane Collaboration and the Agency for Healthcare Research and Quality (AHRQ),
      optimal understanding of SoF table may be influenced by the type of information
      being conveyed and objectives or preferences of the end user. This study aims to
      compare three SoF table formats in terms of understanding, accessibility,
      satisfaction and preference with systematic review users. METHODS: The primary
      objective of this three-arm randomised controlled non-inferiority trial is to
      investigate whether an alternative Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) SoF table or Evidence-based Practice Center
      SoF table is non-inferior to the current GRADE SoF table in the understanding of
      the information presented to systematic review users, particularly for
      descriptive findings. Researchers, clinical practice guideline developers, policy
      makers or knowledge transfer professionals will be recruited. Data will be
      collected electronically at baseline and after randomisation. Non-inferiority
      would be declared if the difference in the proportion of participants who
      understand the information displayed in the alternative SoF table is 10% or less.
      ETHICS AND DISSEMINATION: The Hamilton Integrated Research Ethics Board reviewed
      this protocol. The findings from this study will be disseminated through a
      publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT02813941.

PMID- 29362243
TI  - Diabetes-related behaviours among elderly people with pre-diabetes in rural
      communities of Hunan, China: a cross-sectional study.
AB  - OBJECTIVE: To explore diabetes-related behaviours and their influencing factors
      among elderly individuals with pre-diabetes in rural areas of China. DESIGN,
      SETTING AND PARTICIPANTS: A cross-sectional survey was conducted among elderly
      individuals (>=60 years) in rural communities in Yiyang City of China.
      Multistaged cluster random sampling was carried out to select 42 areas, and
      interviews were conducted among 434 elderly individuals with pre-diabetes
      (fasting plasma glucose 6.1-7.0 mmol/L and/or 2-hour post-glucose load of 7.8
      11.1 mmol/L) using questionnaires on diabetes-related behaviours. The diabetes
      related behaviours included eight categories: average daily sedentary time;
      frequency of physical activities per week; regular or irregular diet; whether
      paying attention to diet control or not; daily dietary preferences; frequency of
      physical examinations per year; current smoking status; and current consumption
      of alcohol. Each of the risky behaviours was scored -1 and each of the healthy
      behaviours was scored +1. Each individual's score of diabetes-related behaviours
      was the sum of the score for all behaviours. MAIN OUTCOME MEASURES: Participants
      were asked about general information (age, gender, marital status, history of
      hyperglycaemia, family history of diabetes mellitus, presence of other diseases,
      body mass index, waist-to-hip ratio and education) and their diabetes-related
      behaviours. Multivariate linear regression analysis was performed to identify the
      risk factors for diabetes-related behaviour among elderly individuals with pre
      diabetes. RESULTS: The average score of diabetes-related behaviours of elderly
      individuals with pre-diabetes in rural China was 2.7. The prevalences of risky
      diabetes-related behaviours were as follows: <1 physical examination per year
      (57.6%), insufficient physical activities (55.3%), lack of attention paid to diet
      control (51.4%), high-salt and high-fat diets (41.0%), sedentary lifestyle
      (35.9%), smoking (22.8%), regular alcohol uptake (15.0%) and irregular diet
      (3.9%). Gender and a history of hyperglycaemia were found to be influencing
      factors of the diabetes-related behaviour score. CONCLUSIONS: The prevalence of
      risky diabetes-related behaviours was high among pre-diabetic elderly individuals
      in rural China. More effort should be made to promote the prevention and control
      of diabetes in rural China. Future studies should be undertaken on diabetes
      prevention strategies tailored specially for this population. TRIAL REGISTRATION
      NUMBER: ChiCTR-IOR-15007033; Results.

PMID- 29362244
TI  - Impact of early palliative care on overall survival of patients with metastatic
      upper gastrointestinal cancers treated with first-line chemotherapy: a randomised
      phase III trial.
AB  - INTRODUCTION: Palliative care (PC) has usually been offered at the end-of-life
      stage, although the WHO recommends providing PC as early as possible in the
      course of the disease. A recent study has shown that early PC (EPC) provides a
      more meaningful effect on quality of life and, surprisingly, on overall survival
      (OS) than standard treatment for patients with metastatic lung cancer. Whether
      EPC benefits also apply to patients with metastatic upper gastrointestinal (GI)
      cancers is unknown. METHODS AND ANALYSIS: EPIC is a randomised phase III trial
      comparing EPC plus standard oncologic care versus standard oncologic care in
      patients with metastatic upper GI cancers. Its primary objective is to evaluate
      the efficacy of EPC in terms of OS. Its secondary objectives are to assess the
      effects of EPC on patient-reported outcomes (quality of life, depression and
      anxiety) and the effect of EPC on the number of patients receiving chemotherapy
      in their last 30 days of life. Assuming an exponential distribution of survival
      time, 381 deaths are required to ensure an 80% power for an absolute difference
      of 10% in 1 year OS rates (40% vs 50.3%, HR=0.75; log rank test two-sided
      alpha=5%), leading to a planned sample size of 480 patients enrolled over 3 years
      and a final analysis at 4 years. The main analysis will be performed on the
      intent-to-treat dataset. ETHICS AND DISSEMINATION: This study was approved by the
      'Comite de Protection des Personnes Nord-Ouest I' (4 April 2016), complies with
      the Helsinki declaration and French laws and regulations and follows the
      International Conference on Harmonisation E6 (R1) Guideline for Good Clinical
      Practice. The trial results, even if they are inconclusive, will be presented at
      international oncology congresses and published in peer-reviewed journals. TRIAL
      REGISTRATION NUMBERS: EudraCT: 2015-A01943-46; Pre-results. NCT02853474.

PMID- 29362245
TI  - Is the association between health-related quality of life and fatigue mediated by
      depression in patients with multiple sclerosis? A Spanish cross-sectional study.
AB  - OBJECTIVES: To determine the mediating effects of depression on health-related
      quality of life and fatigue in individuals with multiple sclerosis (MS). DESIGN:
      A cross-sectional study. SETTING: Tertiary urban hospital. PARTICIPANTS: One
      hundred and eight patients (54% women) with MS participated in this study.
      OUTCOME MEASURES: Demographic and clinical data (weight, height, medication and
      neurological impairment), fatigue (Fatigue Impact Scale), depression (Beck
      Depression Inventory-II) and health-related quality of life (Short-Form Health
      Survey 36) were collected. RESULTS: Fatigue was significantly associated with
      bodily pain, physical function, mental health and depression. Depression was
      associated with bodily pain and mental health. The path analysis found direct
      effects from physical function, bodily pain and depression to fatigue (all,
      P<0.01). The path model analysis revealed that depression exerted a mediator
      effect from bodily pain to fatigue (B=-0.04, P<0.01), and from mental health to
      fatigue (B=-0.16, P<0.01). The amount of fatigue explained by all predictors in
      the path model was 37%. CONCLUSIONS: This study found that depression mediates
      the relationship between some health-related quality of life domains and fatigue
      in people with MS. Future longitudinal studies focusing on proper management of
      depressive symptoms in individuals with MS will help determine the clinical
      implications of these findings.

PMID- 29362246
TI  - Validity of self-reported age at menarche in computer-assisted interview among
      Chinese schoolgirls: a cross-sectional study.
AB  - OBJECTIVE: The attitudes of girls regarding menarche vary according to their
      cultural backgrounds. Asian girls may hesitate to discuss menarche. Computer
      assisted self-administered interviewing (CASI) is considered a valid and
      effective tool for investigating the timing of menarche; however, the validity of
      self-reported menarche data from CASI in Chinese culture is currently unknown. We
      aimed to validate the status and age of menarche attainment by comparing CASI
      with face-to-face interviewing (FFI). METHODS: Based on a cross-sectional study,
      we collected information regarding the status and age of menarche attainment
      using CASI and FFI among Chinese schoolgirls. We explored the tools of standard
      epidemiological indices, including sensitivity, specificity, predictive values
      and accuracy to examine the capacity of CASI for correctly classifying the status
      of menarche. Both Pearson and Spearman correlations were calculated for the
      correlation of age at menarche using CASI with FFI. A Bland-Altman plot was drawn
      to measure the agreement between the two interview techniques. RESULTS: In this
      study, CASI and FFI were conducted in 3478 schoolgirls with an average age (SD)
      of 14.3 years (2.46). Menarche attainment was reported in 2496 (71.2%) and 2538
      (73.0%) girls using CASI and FFI, respectively. Compared with FFI, the
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value and the accuracy of CASI were 0.97, 0.80, 0.96 and 0.92, respectively. The
      correlation of age at menarche between CASI and FFI was 0.728. Approximately >95%
      and 76.3% of the difference in the age at menarche was within 12 months and 3
      months, respectively, between the two interview methods. Among primary
      schoolgirls in grade 5, the sensitivity, specificity, PPV, accuracy and the
      correlation (0.335) of CASI was lower than those in other subgroups. CONCLUSIONS:
      Overall, the timing of menarche investigated using CASI was valid among all
      Chinese schoolgirls, except for those in grade 5 or lower.

PMID- 29362247
TI  - Protocol for a prospective longitudinal study investigating the participation and
      educational trajectories of Australian students with autism.
AB  - INTRODUCTION: Autism is associated with high cost to individuals, families,
      communities and government. Understanding educational and participation
      trajectories during the school years, and factors influencing these, is
      fundamental to reducing financial and personal costs. The primary aim of this
      study is to document the trajectories of Australian students with autism during
      their education. The secondary aim is to examine personal (eg, student skills)
      and environmental (eg, school setting) factors associated with differing
      trajectories and outcomes. METHODS AND ANALYSIS: The cross-sequential
      longitudinal study will recruit two cohorts of 120 parents/caregivers of children
      with autism. Cohort 1 aged between 4 and 5 years and cohort 2 between 9 and 10
      years to start the study. Information will be gathered from parents, teachers and
      school principals at six annual time points (T1 to T6). Parents will be emailed a
      link to an online initial questionnaire (T1) and then contacted annually and
      asked to complete either an extended questionnaire (T3, T5 and T6) or an
      abbreviated questionnaire (T2, T4). Where consent is given, the child's current
      school will be contacted annually (T1 to T6) and teacher and school principal
      asked to complete questionnaires about the child and school. Parent and school
      questionnaires are comprised of questions about demographic and school factors
      that could influence trajectories and a battery of developmental and behavioural
      assessment tools designed to assess educational and participation trajectories
      and outcomes. Surveys will provide longitudinal data on educational and
      participation trajectories for children and adolescents with autism. In addition
      cross-sectional comparisons (within or between age groups) at each time point and
      cohort effects will be explored. ETHICS AND DISSEMINATION: Ethics approvals have
      been granted for this study by all recruiting sites and universities in the
      project. Study findings will inform policy and practice to promote successful
      inclusion and participation of children with autism in education. Results will be
      disseminated through journal publication, conference and seminar presentation.

PMID- 29362248
TI  - Narrative medicine-based intervention in primary care to reduce polypharmacy:
      results from the cluster-randomised controlled trial MultiCare AGENDA.
AB  - OBJECTIVES: To determine if patient-centred communication leads to a reduction of
      the number of medications taken without reducing health-related quality of life.
      DESIGN: Two-arm cluster-randomised controlled trial. SETTING: 55 primary care
      practices in Hamburg, Dusseldorf and Rostock, Germany. PARTICIPANTS: 604 patients
      65 to 84 years of age with at least three chronic conditions. INTERVENTIONS:
      Within the 12-month intervention, general practitioners (GPs) had three 30 min
      talks with each of their patients in addition to routine consultations. The first
      talk aimed at identifying treatment targets and priorities of the patient. During
      the second talk, the medication taken by the patient was discussed based on a
      'brown bag' review of all the medications the patient had at home. The third talk
      served to discuss goal attainment and future treatment targets. GPs in the
      control group performed care as usual. PRIMARY OUTCOME MEASURES: We assumed that
      the number of medications taken by the patient would be reduced by 1.5 substances
      in the intervention group and that the change in the intervention group's health
      related quality of life would not be statistically significantly inferior to the
      control group. RESULTS: The patients took a mean of 7.0+/-3.5 medications at
      baseline and 6.8+/-3.5 medications at follow-up. There was no difference between
      treatment and control group in the change of the number of medications taken
      (0.43; 95% CI -0.07 to 0.93; P=0.094) and no difference in health-related quality
      of life (0.03; -0.02 to 0.08; P=0.207). The likelihood of receiving a new
      prescription for analgesics was twice as high in the intervention group compared
      with the control group (risk ratio, 2.043; P=0.019), but the days spent in
      hospital were reduced by the intervention (-3.07; -5.25 to -0.89; P=0.006).
      CONCLUSIONS: Intensifying the doctor-patient dialogue and discussing the
      patient's agenda and personal needs did not lead to a reduction of medication
      intake and did not alter health-related quality of life. TRIAL REGISTRATION
      NUMBER: ISRCTN46272088; Pre-results.

PMID- 29362249
TI  - Effect of interventions incorporating personalised cancer risk information on
      intentions and behaviour: a systematic review and meta-analysis of randomised
      controlled trials.
AB  - OBJECTIVE: To provide a comprehensive review of the impact on intention to change
      health-related behaviours and health-related behaviours themselves, including
      screening uptake, of interventions incorporating information about cancer risk
      targeted at the general adult population. DESIGN: A systematic review and random
      effects meta-analysis. DATA SOURCES: An electronic search of MEDLINE, EMBASE,
      CINAHL and PsycINFO from 1 January 2000 to 1 July 2017. INCLUSION CRITERIA:
      Randomised controlled trials of interventions including provision of a personal
      estimate of future cancer risk based on two or more non-genetic variables to
      adults recruited from the general population that include at least one
      behavioural outcome. RESULTS: We included 19 studies reporting 12 outcomes. There
      was significant heterogeneity in interventions and outcomes between studies.
      There is evidence that interventions incorporating personalised cancer risk
      information do not affect intention to attend or attendance at screening
      (relative risk 1.00 (0.97-1.03)). There is limited evidence that they increase
      smoking abstinence, sun protection, adult skin self-examination and breast
      examination, and decrease intention to tan. However, they do not increase smoking
      cessation, parental child skin examination or intention to protect skin. No
      studies assessed changes in diet, alcohol consumption or physical activity.
      CONCLUSIONS: Interventions incorporating personalised cancer risk information do
      not affect uptake of screening, but there is limited evidence of effect on some
      health-related behaviours. Further research, ideally including objective measures
      of behaviour, is needed before cancer risk information is incorporated into
      routine practice for health promotion in the general population.

PMID- 29362250
TI  - Randomised controlled trial of a web-based programme in sustaining best practice
      alcohol management practices at community sports clubs: a study protocol.
AB  - INTRODUCTION: Community-based interventions have been found to effectively
      increase the implementation of alcohol management practices and reduce excessive
      alcohol use and alcohol-related harm at sports clubs. However, once
      implementation support ceases there may be a reduction in such intervention
      effects. Thus, ongoing contribution to improving the health of the community is
      diminished; sustaining practice implementation is a key determinant to address
      this. One possible solution to the strategic and logistical challenges of
      sustainability involves the use of the web. The primary aim of this study is to
      assess the effectiveness of a web-based programme in sustaining the
      implementation of alcohol management practices by community football clubs. The
      secondary aim is to assess the effectiveness of the programme in preventing
      excessive alcohol consumption and alcohol-related harm among members of community
      football clubs. METHODS AND ANALYSIS: The study will employ a repeat randomised
      controlled trial design and be conducted in regional and metropolitan areas
      within two states of Australia. Community level football clubs who are currently
      accredited with an existing alcohol management programme ('Good Sports') and
      implementing at least 10 of the 13 core alcohol management practices (eg, not
      serving alcohol to <18-year-olds) required by the programme will be recruited and
      randomised to either a web-based sustainability programme or a 'minimal contact'
      programme. The primary outcome measures are the proportion of football clubs
      implementing >=10 of the 13 required alcohol management practices and the mean
      number of those practices being implemented at 3-year follow-up. Secondary
      outcomes include: the proportion of club members who report risky drinking at
      their club, the Alcohol Use Disorder Identification Test (AUDIT) score and mean
      AUDIT score of club members. Outcome data will be collected via observation at
      the club during a 1-day visit to a home game, conducted by trained research
      assistants at baseline and follow-up. ETHICS AND DISSEMINATION: The study was
      approved by The University of Newcastle Human Research Ethics Committee
      (reference: H-2013-0429). Study findings will be disseminated widely through peer
      reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER:
      ACTRN12614000746639; Pre-results.

PMID- 29362252
TI  - Primary goals, information-giving and men's understanding: a qualitative study of
      Australian and UK doctors' varied communication about PSA screening.
AB  - OBJECTIVES: (1) To characterise variation in general practitioners' (GPs')
      accounts of communicating with men about prostate cancer screening using the
      prostate-specific antigen (PSA) test, (2) to characterise GPs' reasons for
      communicating as they do and (3) to explain why and under what conditions GP
      communication approaches vary. STUDY DESIGN AND SETTING: A grounded theory study.
      We interviewed 69 GPs consulting in primary care practices in Australia (n=40)
      and the UK (n=29). RESULTS: GPs explained their communication practices in
      relation to their primary goals. In Australia, three different communication
      goals were reported: to encourage asymptomatic men to either have a PSA test, or
      not test, or alternatively, to support men to make their own decision. As well as
      having different primary goals, GPs aimed to provide different information (from
      comprehensive to strongly filtered) and to support men to develop different kinds
      of understanding, from population-level to 'gist' understanding. Taking into
      account these three dimensions (goals, information, understanding) and building
      on Entwistle et al's Consider an Offer framework, we derived four overarching
      approaches to communication: Be screened, Do not be screened, Analyse and choose,
      and As you wish. We also describe ways in which situational and relational
      factors influenced GPs' preferred communication approach. CONCLUSION: GPs'
      reported approach to communicating about prostate cancer screening varies
      according to three dimensions-their primary goal, information provision
      preference and understanding sought-and in response to specific practice
      situations. If GP communication about PSA screening is to become more
      standardised in Australia, it is likely that each of these dimensions will
      require attention in policy and practice support interventions.

PMID- 29362251
TI  - Evaluation and management of patients with acute chest pain in China (EMPACT):
      protocol for a prospective, multicentre registry study.
AB  - INTRODUCTION: Acute chest pain represents a major healthcare burden in emergency
      departments (ED) throughout the world. Among these patients, rapidly determining
      whether an acute coronary syndrome (ACS) is evolving remains difficult. In China,
      there are limited data correlating the baseline characteristics, evaluation and
      management of ED patients with acute chest pain and ACS-related symptoms with
      clinical outcomes. Nor has there been an evaluation of outcomes at different
      levels of hospitals. The Evaluation and Management of Patients with Acute ChesT
      pain in China (EMPACT) study will address this evidence gap through a regional
      representative prospective registry. METHODS AND ANALYSIS: Twenty-two public
      hospitals with ED in Shandong province have been selected based on a stratified
      random sampling approach. A total of 10 000 patients with acute chest pain or
      suspected ACS presenting to the ED will be consecutively enrolled from January
      2016 to September 2017. Episodes of care will be evaluated for key performance
      measures such as the time to first ECG, receipt of troponin testing, receipt of
      reperfusion therapy for ST segment elevation ACS and provision of angiography for
      troponin-positive patients. All patients will be assessed for the composite
      endpoint of adjudicated major adverse cardiac events in 30 days after
      presentation, including death from all causes, non-fatal myocardial infarction,
      urgent revascularisation, stroke, cardiac arrest and cardiogenic shock. The
      secondary outcomes include revisit to ED and rehospitalisation within 30 days.
      ETHICS AND DISSEMINATION: Ethics approval was obtained at all participating
      centres. The registry is the first attempt to comprehensively evaluate the
      current emergency care of acute chest pain from a regional representative sample
      in China. Findings will allow new opportunities to facilitate the clinical
      quality improvements and ultimately reduce the mortality in patients with acute
      chest pain and suspected ACS. TRIAL REGISTRATION NUMBER: NCT02536677; Pre
      results.

PMID- 29362253
TI  - Timing of probiotic milk consumption during pregnancy and effects on the
      incidence of preeclampsia and preterm delivery: a prospective observational
      cohort study in Norway.
AB  - OBJECTIVES: To investigate whether the timing of probiotic milk intake before,
      during early or late pregnancy influences associations with preeclampsia and
      preterm delivery. DESIGN: Population based prospective cohort study. SETTING:
      Norway, between 1999 and 2008. PARTICIPANTS: 70 149 singleton pregnancies
      resulting in live-born babies from the Norwegian Mother and Child Cohort Study
      (no chronic disease, answered questionnaires, no placenta previa/cerclage/serious
      malformation of fetus, first enrolment pregnancy). Only nulliparous women (n=37
      050) were included in the preeclampsia analysis. Both iatrogenic and spontaneous
      preterm delivery (between gestational weeks 22+0 and 36+6) with spontaneous term
      controls (between gestational weeks 39+0 and 40+6) were included in the preterm
      delivery analysis resulting in 34 458 cases. MAIN OUTCOME MEASURES: Adjusted OR
      for preeclampsia and preterm delivery according to consumption of probiotic milk
      at three different time periods (before pregnancy, during early and late
      pregnancy). RESULTS: Probiotic milk intake in late pregnancy (but not before or
      in early pregnancy) was significantly associated with lower preeclampsia risk
      (adjusted OR: 0.80 (95% CI 0.68 to 0.94) p-value: 0.007). Probiotic intake during
      early (but not before or during late pregnancy) was significantly associated with
      lower risk of preterm delivery (adjusted OR: 0.79 (0.64 to 0.97) p-value: 0.03).
      CONCLUSIONS: In this observational study, we found an association between timing
      of probiotic milk consumption during pregnancy and the incidence of the adverse
      pregnancy outcomes preeclampsia and preterm delivery. If future randomised
      controlled trials could establish a causal association between probiotics
      consumption and reduced risk of preeclampsia and preterm delivery, recommending
      probiotics would be a promising public health measure to reduce these adverse
      pregnancy outcomes.

PMID- 29362254
TI  - Incremental predictive value of screening for anxiety and depression beyond
      current type 2 diabetes risk models: a prospective cohort study.
AB  - OBJECTIVES: We sought to determine whether screening for anxiety and depression,
      an emerging risk factor for type 2 diabetes (T2D), adds clinically meaningful
      information beyond current T2D risk assessment tools. DESIGN: Prospective cohort.
      PARTICIPANTS AND SETTING: The 45 and Up Study is a large-scale prospective cohort
      of men and women aged 45 years and over, randomly sampled from the general
      population of New South Wales, Australia. 51 588 participants without self
      reported diabetes at baseline (2006-2009) were followed up for approximately 3
      years (2010). METHODS: T2D status was determined by self-reported doctor who
      diagnosed diabetes after the age of 30 years, and/or current use of metformin.
      Current symptoms of anxiety and/or depression were measured by the 10-item
      Kessler Psychological Distress Scale (K10). We determined the optimal cut-off
      point for K10 for predicting T2D using Tjur's R2 and tested risk models with and
      without the K10 using logistic regression. We assessed performance measures for
      the incremental value of the K10 using the area under the receiver operating
      characteristic (AROC), net reclassification improvement (NRI) and net benefit
      (NB) decision analytics with sensitivity analyses. RESULTS: T2D developed in 1076
      individuals (52.4% men). A K10 score of >=19 (prevalence 8.97%), adjusted for age
      and gender, was optimal for predicting incident T2D (sensitivity 77%, specificity
      53% and positive predictive value 3%; OR 1.70 (95% CI 1.41 to 2.03, P<0.001). K10
      score predicted incident T2D independent of current risk models, but did not
      improve corresponding AROC, NRI and NB statistics. Sensitivity analyses showed
      that this was partially explained by the baseline model and the small effect size
      of the K10 that was similar compared with other risk factors. CONCLUSIONS:
      Anxiety and depressing screening with the K10 adds no meaningful incremental
      value in addition to current T2D risk assessments. The clinical importance of
      anxiety and depression screening in preventing T2D requires ongoing
      consideration.

PMID- 29362255
TI  - Evaluating the effectiveness of home exercise programmes using an online exercise
      prescription tool in children with cerebral palsy: protocol for a randomised
      controlled trial.
AB  - INTRODUCTION: Children with cerebral palsy (CP) and other neurodevelopmental
      disabilities often receive a home programme of exercises to assist in reaching
      their therapy goals. Adherence to exercise programmes is necessary to attain the
      level of practice required to achieve goals; however, adherence can be difficult
      to accomplish. In this paper, we describe the protocol for a randomised
      controlled trial to evaluate the effectiveness of delivering a home exercise
      programme to school-age children with disabilities using Physitrack, an online
      exercise prescription tool with a website or app interface. METHODS AND ANALYSIS:
      Participants aged 6-17 years, with CP or other neurodevelopmental disabilities,
      receiving community physiotherapy services in Western Australia, will be
      recruited. Participants will be stratified by age and functional mobility and
      randomised to either the intervention group, who will complete an 8-week home
      exercise programme using Physitrack, or the control group, who will complete an 8
      week exercise programme without Physitrack. Researcher blinding to group
      allocation, and participant blinding to outcome, will be maintained. The primary
      outcome measures are adherence to the home exercise programme with weekly
      collection of home exercise logs; achievement of individualised goals by phone
      interview before and after intervention; and correctness of exercise performance
      by collection and analysis of videos of participants performing home exercises.
      Secondary outcome measures include enjoyment of physical activity, confidence to
      complete exercise programme, preferred method of delivery of programme and
      usability of Physitrack. A sample size of 58 participants will be necessary to
      see an effect on home programme adherence. Data will be analysed using the
      intention-to-treat principle. ETHICS AND DISSEMINATION: Ethical approval was
      obtained from Curtin University Human Research Ethics Committee in July 2016
      (10391). Outcomes will be disseminated through publication in peer-reviewed
      journals and presentations at scientific conferences. TRIAL REGISTRATION NUMBER:
      ACTRN12616000743460; Pre-results.

PMID- 29362256
TI  - The experience of living with patellofemoral pain-loss, confusion and fear
      avoidance: a UK qualitative study.
AB  - OBJECTIVES: To investigate the experience of living with patellofemoral pain
      (PFP). DESIGN: Qualitative study design using semistructured interviews and
      analysed thematically using the guidelines set out by Braun and Clarke. SETTING:
      A National Health Service physiotherapy clinic within a large UK teaching
      hospital. PARTICIPANTS: A convenience sample of 10 participants, aged between 18
      and 40 years, with a diagnosis of PFP and on a physiotherapy waiting list, prior
      to starting physiotherapy. RESULTS: Participants offered rich and detailed
      accounts of the impact and lived experience of PFP, including loss of physical
      and functional ability; loss of self-identity; pain-related confusion and
      difficulty making sense of their pain; pain-related fear, including fear
      avoidance and 'damage' beliefs; inappropriate coping strategies and fear of the
      future. The five major themes that emerged from the data were: (1) impact on
      self; (2) uncertainty, confusion and sense making; (3) exercise and activity
      beliefs; (4) behavioural coping strategies and (5) expectations of the future.
      CONCLUSIONS: These findings offer an insight into the lived experience of
      individuals with PFP. Previous literature has focused on pain and biomechanics,
      rather than the individual experience, attached meanings and any wider context
      within a sociocultural perspective. Our findings suggest that future research is
      warranted into biopsychosocial targeted interventions aimed at the beliefs and
      pain-related fear for people with PFP. The current consensus that best-evidence
      treatments consisting of hip and knee strengthening may not be adequate to
      address the fears and beliefs identified in the current study. Further
      qualitative research may be warranted on the impact and interpretation of medical
      terminology commonly used with this patient group, for example, 'weakness' and
      'patellar mal-tracking' and its impact and interpretation by patients. TRIAL
      REGISTRATION NUMBER: ISRCTN35272486; Pre-results.

PMID- 29362257
TI  - Health outcomes of unpaid care workers in low-income and middle-income countries:
      a protocol for a systematic review.
AB  - INTRODUCTION: The literature on health outcomes of unpaid care work has included
      studies coming from high-income countries, and has reported gender inequalities
      that make caregiving women more vulnerable to physical and mental health
      problems. The impact of unpaid care work on the health of those living in low
      income and middle-income countries, where women's autonomy is more limited, is
      unknown. METHODS AND ANALYSIS: We will conduct a systematic review of
      observational studies on health outcomes according to unpaid caregiving status
      and sex of people living in low-income and middle-income countries. Cumulative
      Index to Nursing and Allied Health Literature, PubMed and Scientific Electronic
      Library Online Citation Index will be searched for reports in English or Spanish
      with published results from inception to 1 June 2017. We expect the studies to
      have recruited individuals in low-income and middle-income countries, including
      exposed and non-exposed groups to participation in unpaid care to members if
      their households or community reporting either physical and/or mental health
      problems, self-reported health-related quality of life, self-care
      skills/behaviours or use of any healthcare services in the participants. Data
      extraction, the assessment of risk of bias and confounding, and qualitative
      synthesis will be carried out by two independent reviewers with the assistance of
      a third party. DISSEMINATION: Results are expected to be published in peer
      reviewed journals from the field of health and gender, or health and inequality.
      PROSPERO REGISTRATION NUMBER: CRD42017071785.

PMID- 29362258
TI  - Cost-effectiveness of FreeO2 in patients with chronic obstructive pulmonary
      disease hospitalised for acute exacerbations: analysis of a pilot study in
      Quebec.
AB  - OBJECTIVE: Conduct a cost-effectiveness analysis of FreeO2 technology versus
      manual oxygen-titration technology for patients with chronic obstructive
      pulmonary disease (COPD) hospitalised for acute exacerbations. SETTING: Tertiary
      acute care hospital in Quebec, Canada. PARTICIPANTS: 47 patients with COPD
      hospitalised for acute exacerbations. INTERVENTION: An automated oxygen-titration
      and oxygen-weaning technology. METHODS AND OUTCOMES: The costs for
      hospitalisation and follow-up for 180 days were calculated using a microcosting
      approach and included the cost of FreeO2 technology. Incremental cost
      effectiveness ratios (ICERs) were calculated using bootstrap resampling with 5000
      replications. The main effect variable was the percentage of time spent at the
      target oxygen saturation (SpO2). The other two effect variables were the time
      spent in hyperoxia (target SpO2+5%) and in severe hypoxaemia (SpO2 <85%). The
      resamplings were based on data from a randomised controlled trial with 47
      patients with COPD hospitalised for acute exacerbations. RESULTS: FreeO2
      generated savings of 20.7% of the per-patient costs at 180 days (ie, -$C2959.71).
      This decrease is nevertheless not significant at the 95% threshold (P=0.13), but
      the effect variables all improved (P<0.001). The improvement in the time spent at
      the target SpO2 was 56.3%. The ICERs indicate that FreeO2 technology is more cost
      effective than manual oxygen titration with a savings of -$C96.91 per percentage
      point of time spent at the target SpO2 (95% CI -301.26 to 116.96). CONCLUSION:
      FreeO2 technology could significantly enhance the efficiency of the health system
      by reducing per-patient costs at 180 days. A study with a larger patient sample
      needs to be carried out to confirm these preliminary results. TRIAL REGISTRATION
      NUMBER: NCT01393015; Post-results.

PMID- 29362259
TI  - Prognostic factors of inhospital death in elderly patients: a time-to-event
      analysis of a cohort study in Martinique (French West Indies).
AB  - OBJECTIVE: The primary objective was to identify predictive factors of inhospital
      death in a population of patients aged 65 years or older hospitalised with
      Chikungunya virus (CHIKV) infection. The secondary aim was to develop and
      validate a predictive score for inhospital death based on the predictors
      identified. DESIGN: Longitudinal retrospective study from January to December
      2014. SETTING: University Hospital of Martinique. PARTICIPANTS: Patients aged
      >=65 years, admitted to any clinical ward and who underwent reverse transcription
      PCR testing for CHIKV infection. OUTCOME: Independent predictors of inhospital
      death were identified using multivariable Cox regression modelling. A predictive
      score was created using the adjusted HRs of factors associated with inhospital
      death. Receiver operating characteristic curve analysis was used to determine the
      best cut-off value. Bootstrap analysis was used to evaluate internal validity.
      RESULTS: Overall, 385 patients aged >=65 years were included (average age: 80+/-8
      years). Half were women, and 35 (9.1%) died during the hospital stay. Seven
      variables were found to be independently associated with inhospital death
      (concurrent cardiovascular disorders: HR 11.8, 95% CI 4.5 to 30.8; concurrent
      respiratory infection: HR 9.6, 95% CI 3.4 to 27.2; concurrent sensorimotor
      deficit: HR 7.6, 95% CI 2.0 to 28.5; absence of musculoskeletal pain: HR 2.6, 95%
      CI 1.3 to 5.3; history of alcoholism: HR 2.5, 95% CI 1.1 to 5.9; concurrent
      digestive symptoms: HR 2.4, 95% CI 1.2 to 4.9; presence of confusion or delirium:
      HR 2.1, 95% CI 1.1 to 4.2). The score ranged from 0 to 25, with an average of 6+/
      6. The area under the curve was excellent (0.90; 95% CI 0.86 to 0.94). The best
      cut-off value was a score >=8 points, with a sensitivity of 91% (82%-100%) and
      specificity of 75% (70%-80%). CONCLUSIONS: Signs observed by the clinician during
      the initial examination could predict inhospital death. The score will be helpful
      for early management of elderly subjects presenting within 7 days of symptom
      onset in the context of CHIKV outbreaks.

PMID- 29362260
TI  - Cluster randomised controlled trial of a multicomponent intervention to support
      the implementation of policies and practices that promote healthier environments
      at junior sports clubs: study protocol.
AB  - INTRODUCTION: A large proportion of children and adolescents participate in
      organised sport, making community sports clubs a promising setting to support
      healthy behaviours. To date, however, there have been few interventions conducted
      in junior sports clubs that have targeted health-promoting practices. The primary
      aim of this pilot study is to assess the potential effectiveness of an
      intervention to implement health-promoting policies and practices in junior
      sporting clubs targeting alcohol and tobacco practices, healthy food and beverage
      availability, and physical activity via participation in sport. A secondary
      outcome is to assess the impact of such strategies on child exposure to alcohol
      and tobacco use at the club, purchasing behaviours by/for children at the club
      canteen and child sports participation opportunities. METHODS AND ANALYSIS: The
      study will employ a cluster randomised controlled trial design and be conducted
      in metropolitan and regional areas of two Australian states. Randomisation will
      occur at the level of the football league. Community football clubs with over 40
      junior players (players under 18 years) within each league will be eligible to
      participate. The intervention will be developed based on frameworks that consider
      the social, cultural and environmental factors that influence health behaviours.
      Intervention clubs will be supported to implement 16 practices targeting alcohol
      management, tobacco use, nutrition practices, new player recruitment activity,
      equal participation for players and the development of policies to support these
      practices. Trained research staff will collect outcome data via telephone
      interviews at baseline and follow-up. Interviews will be conducted with both club
      representatives and parents of junior players. ETHICS AND DISSEMINATION: The
      study has been approved by the University of Newcastle Human Research Ethics
      Committee (H-2013-0429). The results of the study will be disseminated via peer
      reviewed publications and presentations at conferences. TRIAL REGISTRATION
      NUMBER: ACTRN12617001044314; Pre-results.

PMID- 29362261
TI  - Resource utilisation and costs in predementia and dementia: a systematic review
      protocol.
AB  - INTRODUCTION: Dementia is the fastest growing major cause of disability globally
      with a mounting social and financial impact for patients and their families but
      also to health and social care systems. This review aims to systematically
      synthesise evidence on the utilisation of resources and costs incurred by
      patients and their caregivers and by health and social care services across the
      full spectrum of dementia, from its preceding preclinical stage to end of life.
      The main drivers of resources used and costs will also be identified. METHODS AND
      ANALYSIS: A systematic literature review was conducted in MEDLINE, EMBASE, CDSR,
      CENTRAL, DARE, EconLit, CEA Registry, TRIP, NHS EED, SCI, RePEc and OpenGrey
      between January 2000 and beginning of May 2017. Two reviewers will independently
      assess each study for inclusion and disagreements will be resolved by a third
      reviewer. Data will be extracted using a predefined data extraction form
      following best practice. Study quality will be assessed with the Effective Public
      Health Practice Project quality assessment tool. The reporting of costing
      methodology will be assessed using the British Medical Journal checklist. A
      narrative synthesis of all studies will be presented for resources used and costs
      incurred, by level of disease severity when available. If feasible, the data will
      be synthesised using appropriate statistical techniques. ETHICS AND
      DISSEMINATION: Included articles will be reviewed for an ethics statement. The
      findings of the review will be disseminated in a related peer-reviewed journal
      and presented at conferences. They will also contribute to the work developed in
      the Real World Outcomes across the Alzheimer's disease spectrum for better care:
      multi-modal data access platform (ROADMAP). TRIAL REGISTRATION NUMBER:
      CRD42017071413.

PMID- 29362262
TI  - Validation of intellectual disability coding through hospital morbidity records
      using an intellectual disability population-based database in Western Australia.
AB  - OBJECTIVES: To investigate how well intellectual disability (ID) can be
      ascertained using hospital morbidity data compared with a population-based data
      source. DESIGN, SETTING AND PARTICIPANTS: All children born in 1983-2010 with a
      hospital admission in the Western Australian Hospital Morbidity Data System
      (HMDS) were linked with the Western Australian Intellectual Disability Exploring
      Answers (IDEA) database. The International Classification of Diseases hospital
      codes consistent with ID were also identified. MAIN OUTCOME MEASURES: The
      characteristics of those children identified with ID through either or both
      sources were investigated. RESULTS: Of the 488 905 individuals in the study, 10
      218 (2.1%) were identified with ID in either IDEA or HMDS with 1435 (14.0%)
      individuals identified in both databases, 8305 (81.3%) unique to the IDEA
      database and 478 (4.7%) unique to the HMDS dataset only. Of those unique to the
      HMDS dataset, about a quarter (n=124) had died before 1 year of age and most of
      these (75%) before 1 month. Children with ID who were also coded as such in the
      HMDS data were more likely to be aged under 1 year, female, non-Aboriginal and
      have a severe level of ID, compared with those not coded in the HMDS data. The
      sensitivity of using HMDS to identify ID was 14.7%, whereas the specificity was
      much higher at 99.9%. CONCLUSION: Hospital morbidity data are not a reliable
      source for identifying ID within a population, and epidemiological researchers
      need to take these findings into account in their study design.

PMID- 29362263
TI  - Protocol for a feasibility trial for improving breast feeding initiation and
      continuation: assets-based infant feeding help before and after birth (ABA).
AB  - INTRODUCTION: Breast feeding improves the health of mothers and infants; the UK
      has low rates, with marked socioeconomic inequalities. While trials of peer
      support services have been effective in some settings, UK trials have not
      improved breast feeding rates. Qualitative research suggests that many women are
      alienated by the focus on breast feeding. We propose a change from breast feeding
      focused interactions to respecting a woman's feeding choices, inclusion of
      behaviour change theory and an increased intensity of contacts in the 2 weeks
      after birth when many women cease to breast feed. This will take place alongside
      an assets-based approach that focuses on the positive capability of individuals,
      their social networks and communities.We propose a feasibility study for a
      multicentre randomised controlled trial of the Assets feeding help Before and
      After birth (ABA) infant feeding service versus usual care. METHODS AND ANALYSIS:
      A two-arm, non-blinded randomised feasibility study will be conducted in two UK
      localities. Women expecting their first baby will be eligible, regardless of
      feeding intention. The ABA infant feeding intervention will apply a proactive,
      assets-based, woman-centred, non-judgemental approach, delivered antenatally and
      postnatally tailored through face-to-face contacts, telephone and SMS texts.
      Outcomes will test the feasibility of delivering the intervention with
      recommended intensity and duration to disadvantaged women; acceptability to
      women, feeding helpers and professionals; and feasibility of a future randomised
      controlled trial (RCT), detailing recruitment rates, willingness to be
      randomised, follow-up rates at 3 days, 8 weeks and 6 months, and level of outcome
      completion. Outcomes of the proposed full trial will also be collected. Mixed
      methods will include qualitative interviews with women/partners, feeding helpers
      and health service staff; feeding helper logs; and review of audio-recorded
      helper-women interactions to assess intervention fidelity. ETHICS AND
      DISSEMINATION: Study results will inform the design of a larger multicentre RCT.
      The National Research Ethics Service Committee approved the study protocol. TRIAL
      REGISTRATION NUMBER: ISRCTN14760978; Pre-results.

PMID- 29362264
TI  - Growth across life course and cardiovascular risk markers in 18-year-old
      adolescents: the 1993 Pelotas birth cohort.
AB  - OBJECTIVE: To evaluate the association between growth trajectories from birth to
      adolescence and cardiovascular risk marker levels at age 18 years in a population
      based cohort. In order to disentangle the effect of weight gain from that of
      height gain, growth was analysed using conditional weight relative to linear
      growth (CWh) and conditional length/height (CH). DESIGN: Prospective study.
      SETTING: 1993 Pelotas birth cohort, Southern Brazil. PARTICIPANTS: Individuals
      who have been followed up from birth to adolescence (at birth, 1, 4, 11, 15 and
      18 years). PRIMARY OUTCOME MEASURES: C-reactive protein (CRP), total cholesterol
      (TC), LDL cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TGL),
      systolic and diastolic blood pressure (SBP and DBP), body mass index (BMI) and
      waist circumference (WC). RESULTS: In both sexes, greater CWh at 1 year was
      positively associated with BMI and WC, whereas greater CWh at most age periods in
      childhood and adolescence predicted higher CRP, TC, LDL-C, TGL, SBP, DBP, BMI and
      WC levels, as well as lower HDL-C level. Higher CH during infancy and childhood
      was positively related with SBP in boys and girls, and with BMI and WC only in
      boys. CONCLUSION: Our study shows that rapid weight gain from 1 year onwards is
      positively associated with several markers of cardiovascular risk at 18 years.
      Overall, our results for the first year of life add evidence to the 'first 1000
      days initiative' suggesting that prevention of excessive weight gain in childhood
      might be important in reducing subsequent cardiovascular risk.

PMID- 29362265
TI  - Protocol for the systematic review of the reporting of transoral robotic surgery.
AB  - INTRODUCTION: Transoral robotic surgery (TORS) has been adopted in some parts of
      the world as an innovative approach to the resection of oropharyngeal tumours.
      The development, details and outcomes of early-to-later phase evaluation of this
      technique and the quality of evidence to support its adoption into practice have
      hitherto not been summarised. The aim of this review is to identify and summarise
      the early and later phase studies of, and evidence for, TORS and to understand
      how early phase studies report intervention development, governance procedures
      and selection and reporting of outcomes to optimise methods for using the Idea,
      Development, Exploration, Assessment, Long-term follow-up (IDEAL) framework for
      surgical innovation that informs evidence-based practice. The protocol has been
      written in line with the Preferred Reporting Items for Systematic Review and Meta
      Analysis Protocols checklist. METHODS AND ANALYSIS: Electronic searches in OVID
      SP versions of Medline and EMBASE, the Cochrane Central Register of Controlled
      Trials and the Cochrane Database of Systematic Reviews from the start of indexing
      to 30 April 2017 will identify studies reporting TORS. At least two independent
      researchers will identify studies for inclusion. Two researchers will extract
      data from each paper. Studies will be categorised into IDEAL stages of study
      design from 'pre-IDEAL' to randomised controlled trials (stage 3). Data will be
      collected about the (1) novel intervention and criteria for modification, (2)
      governance arrangements and patient information provision, (3) outcome domains
      selected and reported and (4) quality of study design, conduct and reporting.
      Descriptive statistics and a narrative synthesis will be presented. ETHICS AND
      DISSEMINATION: The results of this systematic review will be presented at
      relevant conferences. The methods will be used to inform future reviews exploring
      other novel surgical innovations. The findings will be published in a peer
      reviewed journal. This study does not require ethical approval.

PMID- 29362266
TI  - Patient-centred attitudes among medical students in Mali, West Africa: a cross
      sectional study.
AB  - BACKGROUND/OBJECTIVE: Patient-centred attitudes have been shown to decline during
      medical training in high-income countries, yet little is known about attitudes
      among West African medical students. We sought to measure student attitudes
      towards patient-centredness and examine validity of the 18-item Patient
      Practitioner Orientation Scale (PPOS) in this context. PARTICIPANTS/SETTING: 430
      medical students in years 1, 3, 5 and 6 of a 6-year medical training programme in
      Bamako, Mali. DESIGN: We conducted a cross-sectional survey, compared the
      proportion of students who agreed with each PPOS item by gender and academic
      year, and calculated composite PPOS scores. To examine psychometrics of the PPOS
      and its two subscales ('sharing' and 'caring'), we calculated internal
      consistency (Cronbach's alpha) and performed confirmatory and exploratory factor
      analyses (CFA and EFA). RESULTS: In seven of the nine 'sharing' items, the
      majority of students held attitudes favouring a provider-dominant style. For five
      of the nine 'caring' items, the majority of student responded consistently with
      patient-centred attitudes, while in the other four, responses indicated a disease
      centred orientation. In eight items, a greater proportion of fifth/sixth year
      students held patient-centred attitudes as compared with first year students;
      there were few gender differences. Average PPOS scores indicated students were
      moderately patient-centred, with more favourable attitudes towards the 'caring'
      aspect than 'sharing'. Internal consistency of the PPOS was inadequate for the
      full scale (alpha=0.58) and subscales ('sharing' alpha=0.37; 'caring'
      alpha=0.48). CFA did not support the original PPOS factors and EFA did not
      identify an improved structure. CONCLUSIONS: West African medical students
      training in Bamako are moderately patient-centred and do not show the same
      declines in patient-centred attitudes in higher academic years as seen in other
      settings. Medical students may benefit from training in shared power skills and
      in attending to patient lifestyle factors. Locally validated tools are needed to
      guide West African medical schools in fostering patient-centredness among
      students.

PMID- 29362267
TI  - Parathyroid hormone analogues for fracture healing: protocol for a systematic
      review and meta-analysis of randomised controlled trials.
AB  - INTRODUCTION: Fracture healing is a complex physiological process. Impaired
      healing will increase the need for care and cause serious complications. Thus,
      identifying strategies to accelerate the rate of healing, preventing delayed
      unions and non-unions, is essential. Parathyroid hormone (PTH) is a key systemic
      regulator of calcium and phosphate metabolism. It has been determined that
      intermittent administration of PTH and its analogue can exert anabolic effect on
      bone, increase bone mass and reduce bone loss, leading to an increase in bone
      formation. Owing to their anabolic effect, there is an increasing interest in its
      potential in promoting the process of fracture healing. However, in clinical
      studies, the results are in conflict. This objective of this study is to
      determine the role of PTH analogues for fracture healing in adults. METHODS AND
      ANALYSIS: MEDLINE, EMBASE and Cochrane databases will be searched to identify all
      randomised controlled trials (RCTs) and quasi-RCTs that compare the different
      effects between PTH analogues and any other treatments in adults with any type of
      fracture. The primary outcome is the functional recovery. And the secondary
      outcomes are fracture union and adverse events. The meta-analysis will be
      performed using a random effects model. Heterogeneity will be assessed by the P
      values and I2 statistic. And subgroup analyses and sensitivity analyses will be
      used to explore the heterogeneity. Risk of bias will be assessed using the
      Cochrane tool and the quality of evidence will be assessed using the Grading of
      Recommendations Assessment, Development and Evaluation approach. ETHICS AND
      DISSEMINATION: Ethical approval is not required because this proposed systematic
      review and meta-analysis is based on published data, without including
      confidential personal data or data on interventions on patients. The findings of
      this study will be published in a peer-reviewed journaland presented at a
      relevant conference. PROSPERO REGISTRATION NUMBER: CRD42017062093.

PMID- 29362268
TI  - Expanded cardiac rehabilitation in socially vulnerable patients with myocardial
      infarction: a 10-year follow-up study focusing on mortality and non-fatal events.
AB  - OBJECTIVE: Cardiac rehabilitation (CR) has been shown to reduce cardiovascular
      risk. A research project performed at a university hospital in Denmark offered an
      expanded CR intervention to socially vulnerable patients. One-year follow-up
      showed significant improvements concerning medicine compliance, lipid profile,
      blood pressure and body mass index when compared with socially vulnerable
      patients receiving standard CR. The aim of the study was to perform a long-term
      follow-up on the socially differentiated CR intervention and examine the impact
      of the intervention on all-cause mortality, cardiovascular mortality, non-fatal
      recurrent events and major cardiac events (MACE) 10 years after. DESIGN:
      Prospective cohort study. SETTING: The cardiac ward at a university hospital in
      Denmark from 2000 to 2004. PARTICIPANTS: 379 patients aged <70 years admitted
      with first episode myocardial infarction (MI). The patients were defined as
      socially vulnerable or non-socially vulnerable according to their educational
      level and their social network. A complete follow-up was achieved. INTERVENTION:
      A socially differentiated CR intervention. The intervention consisted of standard
      CR and additionally a longer phase II course, more consultations, telephone
      follow-up and a better handover to phase III CR in the municipal sector, in
      general practice and in the patient association. MAIN OUTCOME MEASURES: All-cause
      mortality, cardiovascular mortality, non-fatal recurrent events and MACE.
      RESULTS: There was no significant difference in all-cause mortality (OR: 1.29,
      95% CI 0.58 to 2,89), cardiovascular mortality (OR: 0.80, 95% CI 0.31 to 2.09),
      non-fatal recurrent events (OR:1.62, 95% CI 0.67 to 3.92) or MACE (OR: 1.31, 95%
      CI 0.53 to 2.42) measured at 10-year follow-up when comparing the expanded CR
      intervention to standard CR. CONCLUSIONS: Despite the significant results of the
      socially differentiated CR intervention at 1-year follow-up, no long-term effects
      were seen regarding the main outcome measures at 10-year follow-up. Future
      research should focus on why it is not possible to lower the mortality and
      morbidity significantly among socially vulnerable patients admitted with first
      episode MI.

PMID- 29362269
TI  - PlenadrEMA: effect of dual-release versus conventional hydrocortisone on fatigue,
      measured by ecological momentary assessments: a study protocol for an open-label
      switch pilot study.
AB  - INTRODUCTION: Patients with adrenal insufficiency have impaired health-related
      quality of life (QoL). The dual-release hydrocortisone preparation, Plenadren,
      has been developed to mimic the physiological cortisol release more closely than
      conventional hydrocortisone treatment. Plenadren has been shown to improve QoL,
      in particular fatigue, in patients with primary adrenal insufficiency. However,
      the effect has not been investigated in patients with secondary adrenal
      insufficiency; furthermore, no study has taken the diurnal variation of fatigue
      into account. To assess diurnal variations, it is necessary to use repeated daily
      measurements, such as ecological momentary assessments (EMAs). This study aims to
      evaluate EMAs of fatigue as outcome in future large-scale randomised clinical
      trials. METHODS AND ANALYSIS: The PlenadrEMA trial is an investigator-initiated
      open-label switch pilot trial of the effect of Plenadren versus conventional
      hydrocortisone on fatigue in patients with secondary adrenal insufficiency. The
      trial will include 30 participants. After 5 weeks on their usual hydrocortisone
      treatment, patients will be shifted to Plenadren for 16 weeks. Fatigue will be
      assessed using momentary versions of the Multidimensional Fatigue Inventory (MFI
      20). Items will be administered to participants via a smartphone application four
      times daily during 20 days. Assessments will be performed before treatment shift
      and repeated after 12.5 weeks on Plenadren. The study will identify the best
      suited outcome for future randomised clinical trials, and in addition, estimate
      the variability and difference in fatigue between the two treatments to perform
      power calculations. ETHICS AND DISSEMINATION: The trial will be conducted in
      accordance with the Declaration of Helsinki and has been approved by the Regional
      Scientific Ethical Committee in Copenhagen (ID: H-1-2014-073). All patients will
      receive written and verbal information about the trial and will give informed
      consent before enrolment. Findings will be published in peer-reviewed journals
      and presented at international conferences. TRIAL REGISTRATION NUMBER:
      EudraCT201400203932.

PMID- 29362270
TI  - Inversed relationship between completeness of follow-up and coverage of
      postoperative complications in gallstone surgery and ERCP: a potential source of
      bias in patient registers.
AB  - OBJECTIVE: To analyse the completeness in GallRiks of the follow-up frequency in
      relation to the intraoperative and postoperative outcome. DESIGN: Population
      based register study. SETTING: Data from the national Swedish Registry for
      Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography (ERCP),
      GallRiks. POPULATION: All cholecystectomies and ERCPs recorded in GallRiks
      between 1 January 2006 and 31 December 2014. MAIN OUTCOME MEASURES: Outcomes for
      intraprocedural as well as postprocedural adverse events between units with
      either a 30-day follow-up of >=90% compared with those with a less frequent
      follow-up (<90%). RESULTS: Between 2006 and 2014, 162 212 cholecystectomies and
      ERCP procedures were registered in GallRiks. After the exclusion of non-index
      procedures and those with incomplete data 152 827 procedures remained for final
      analyses. In patients having a cholecystectomy, there were no differences
      regarding the adverse event rates, irrespective of the follow-up frequency.
      However, in the more complicated endoscopic ERCP procedures, the postoperative
      adverse event rates were significantly higher in those with a more frequent and
      complete 30-day follow-up (OR 1.92; 95% CI 1.76 to 2.11). CONCLUSIONS:
      Differences in the follow-up frequency in registries affect the reported outcomes
      as exemplified by the complicated endoscopic ERCP procedures. A high and complete
      follow-up rate shall serve as an additional quality indicator for surgical
      registries.

PMID- 29362271
TI  - Does vitamin D supplementation improve bone density in vitamin D-deficient
      children? Protocol for an individual patient data meta-analysis.
AB  - INTRODUCTION: Our previous study-level (aggregate data) meta-analysis suggested
      that vitamin D supplements may be beneficial for bone density specifically in
      children with vitamin D deficiency. However, the misclassification of vitamin D
      status inherent in study-level data means that the results are not definitive and
      cannot provide an accurate assessment of the size of any effect. Therefore, we
      propose to undertake an individual patient data (IPD) meta-analysis to determine
      whether the effect of vitamin D supplementation on bone density in children
      differs according to baseline vitamin D status, and to specifically estimate the
      effect of vitamin D in children who are vitamin D deficient. METHODS AND
      ANALYSIS: This study has been designed to adhere to the Preferred Reporting Items
      for Systematic Review and Meta-Analyses of IPD statement. We will include
      randomised placebo-controlled trials of vitamin D supplementation reporting bone
      density outcomes at least 6 months after the study commenced in children and
      adolescents (aged <20 years) without coexistent medical conditions or treatments
      causing osteoporosis. We will update the search of the original review to cover
      the period 2009-2017, using the same methods as the original review. Fully
      anonymised data on all randomised patients will be requested. Outcomes will be
      femoral neck, total hip, lumbar spine and proximal and distal forearm bone
      mineral density, and total body bone mineral content. A two-stage IPD meta
      analysis will be used to examine the effect of baseline serum 25-hydroxyvitamin D
      (25(OH)D) on treatment effect for each bone density outcome. Restricted maximum
      likelihood will be used to estimate the random-effects meta-analysis models, with
      95% CI for summary effects. Heterogeneity will be assessed by I2 and potential
      publication bias (small-study effects) and availability bias by funnel plots,
      Egger's test and Peter's test. ETHICS AND DISSEMINATION: Ethics approval will not
      be required as the data are to be used for the primary purpose for which they
      were collected and all original individual studies had ethics approval. Results
      of the IPD meta-analysis will be submitted for publication in a peer-reviewed
      journal. PROSPERO REGISTRATION NUMBER: CRD42017068772.

PMID- 29362273
TI  - How does the outcome of research training fellowships funded via the NHS compare
      with that from competitively funded fellowships from the MRC and other charities:
      a cross-sectional retrospective survey of trainees undertaking research training
      in the West Midlands.
AB  - OBJECTIVES: This study aimed to investigate the impact of research training
      funded via the National Health Service (NHS) on medical trainees compared with
      traditional clinical research training fellowships (CRTFs). DESIGN, SETTING AND
      PARTICIPANTS: Online survey of 221 clinical trainees who had completed a period
      of research during their clinical training between 2009 and 2015 in the West
      Midlands. MAIN OUTCOME MEASURES: Research outcomes. RESULTS: Overall response
      rate was 59%, of whom 72 participants were funded by CRTFs and 51 funded by the
      NHS. Although participants with CRTFs were more likely to be awarded a higher
      degree compared with those on NHS-administered funding (66/72 CRTFs and 37/51
      NHS, P=0.005), similar proportions of NHS-funded and CRTF-funded participants
      entered clinical lecturer posts on completing initial research training (8/51 NHS
      and 16/72 CRTF, P=0.37). 77% of participants had three or more publications (CRTF
      57 and NHS 39, P=0.72). 57 participants had completed clinical training; similar
      proportions of CRTF-funded and NHS-funded trainees had research included in their
      consultant contract (12/22 NHS and 14/26 CRTF, P=0.96) or were appointed to
      academic posts (3 of 25 NHS funded and 6 of 32 CRTF, P>0.05). 95% of participants
      would recommend to colleagues and 82% of participants felt the research
      experience improved their provision of clinical care with no difference between
      CRTF-funded and NHS-funded participants (P=0.49). Continuing to participate in
      clinical work during the research reduced reports of trainee difficulty on
      returning to clinical work (23/108 continued clinical work vs 12/22 no clinical
      work, P=0.001). CONCLUSION: Research training funded by the NHS provides a
      quality experience and contributes to the clinical academic capacity within the
      UK. More needs to be done to support NHS participants to successfully achieve a
      higher degree.

PMID- 29362272
TI  - What fluids are given during air ambulance treatment of patients with trauma in
      the UK, and what might this mean for the future? Results from the RESCUER
      observational cohort study.
AB  - OBJECTIVES: We investigated how often intravenous fluids have been delivered
      during physician-led prehospital treatment of patients with hypotensive trauma in
      the UK and which fluids were given. These data were used to estimate the
      potential national requirement for prehospital blood products (PHBP) if evidence
      from ongoing trials were to report clinical superiority. SETTING: The Regional
      Exploration of Standard Care during Evacuation Resuscitation (RESCUER)
      retrospective observational study was a collaboration between 11 UK air ambulance
      services. Each was invited to provide up to 5 years of data and total number of
      taskings during the same period. PARTICIPANTS: Patients with hypotensive trauma
      (systolic blood pressure <90 mm Hg or absent radial pulse) attended by a doctor.
      PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the number of
      patients with hypotensive trauma given prehospital fluids. Secondary outcomes
      were types and volumes of fluids. These data were combined with published data to
      estimate potential national eligibility for PHBP. RESULTS: Of 29 037 taskings,
      729 (2.5%) were for patients with hypotensive trauma attended by a physician.
      Half were aged 21-50 years; 73.4% were male. A total of 537 out of 729 (73.7%)
      were given fluids. Five hundred and ten patients were given a single type of
      fluid; 27 received >1 type. The most common fluid was 0.9% saline, given to
      486/537 (90.5%) of patients who received fluids, at a median volume of 750 (IQR
      300-1500) mL. Three per cent of patients received PHBP. Estimated projections for
      patients eligible for PHBP at these 11 services and in the whole UK were 313 and
      794 patients per year, respectively. CONCLUSIONS: One in 40 air ambulance
      taskings were manned by physicians to retrievepatients with hypotensive trauma.
      The most common fluid delivered was 0.9% saline. If evidence justifies universal
      provision of PHBP, approximately 800 patients/year would be eligible in the UK,
      based on our data combined with others published. Prospective investigations are
      required to confirm or adjust these estimations.

PMID- 29362274
TI  - Effect of differentiating exercise guidance based on a patient's level of low
      back pain in primary care: a mixed-methods systematic review protocol.
AB  - INTRODUCTION: Low back pain (LBP) is one of the health conditions that lead to
      the most disability worldwide. Guidelines aimed at management of LBP recommend
      non-invasive and non-pharmacological management, including patient education,
      advice to stay active and exercise therapy; however, the guidelines offer no
      recommendation as to the allowable level of pain during exercise or how specific
      levels of pain should be reflected in the stage and progression of exercises or
      activities. The purpose of this review is to study the effect of differentiation
      of exercise guidance based on the level of LBP in patients in primary care.
      METHODS AND ANALYSIS: A systematic search will be performed on PubMed, EMBASE,
      The Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO,
      Physiotherapy Evidence Database (PEDRO), Cochrane and PROSPERO from their
      inception until September 2017. Published peer-reviewed human experimental and
      observational studies with quantitative or qualitative designs will be included.
      Two independent reviewers will identify papers by reviewing titles and abstracts.
      Papers passing the initial selection will be appraised by two reviewers, based on
      their full texts. Furthermore, the reference lists of included studies will be
      snowballed for identification of other relevant studies. Data will be extracted
      using a standard extraction sheet by two independent reviewers. Disagreements
      will be resolved by discussion and consensus with a third reviewer. The
      methodological quality of studies will be assessed using the Grading of
      Recommendations, Assessment, Development and Evaluation risk of bias tool, or the
      Critical Appraisal Skills Programme. Results will be reported narratively. Search
      histories will be documented on EndNote X8 (Clarivate Analytics). ETHICS AND
      DISSEMINATION: Ethical approval for this review was not required as primary data
      will not be collected. The results will be disseminated through a peer-reviewed
      international journal and conference presentations. PROSPERO REGISTRATION NUMBER:
      CRD42017074880.

PMID- 29362275
TI  - Investigation assessing the publicly available evidence supporting postmarketing
      withdrawals, revocations and suspensions of marketing authorisations in the EU
      since 2012.
AB  - OBJECTIVES: To assess the sources of publicly available evidence supporting
      withdrawal, revocation or suspension of marketing authorisations ('regulatory
      actions') due to safety reasons in the EU since 2012 and to investigate the time
      taken since initial marketing authorisation to reach these regulatory decisions.
      SETTING: This investigation examined the sources of evidence supporting 18
      identified prescription medicinal products which underwent regulatory action due
      to safety reasons within the EU in the period 1 July 2012 to 31 December 2016.
      RESULTS: Eighteen single or combined active substances ('medicinal products')
      withdrawn, revoked or suspended within the EU for safety reasons between 2012 and
      2016 met the inclusion criteria. Case reports were most commonly cited,
      supporting 94.4% of regulatory actions (n=17), followed by randomised controlled
      trial, meta-analyses, animal and in vitro, ex vivo or in silico study designs,
      each cited in 72.2% of regulatory actions (n=13). Epidemiological study designs
      were least commonly cited (n=8, 44.4%). Multiple sources of evidence contributed
      to 94.4% of regulatory decisions (n=17). Death was the most common adverse drug
      reaction leading to regulatory action (n=5; 27.8%), with four of these related to
      medication error or overdose. Median (IQR) time taken to reach a decision from
      the start of regulatory review was found to be 204.5 days (143, 535 days) and
      decreased across the study period. Duration of marketing prior to regulatory
      action, from the medicinal product's authorisation date, increased across the
      period 2012-2016. CONCLUSIONS: The sources of evidence supporting
      pharmacovigilance regulatory activities appear to have changed since
      implementation of Directive 2010/84/EU and Regulation (EU) No. 1235/2010. This,
      together with a small improvement in regulatory efficiency, suggests progress
      towards more rapid regulatory decisions based on more robust evidence. Future
      research should continue to monitor sources of evidence supporting regulatory
      decisions and the time taken to reach these decisions over time.

PMID- 29362276
TI  - Interdisciplinary collaboration across secondary and primary care to improve
      medication safety in the elderly (IMMENSE study): study protocol for a randomised
      controlled trial.
AB  - INTRODUCTION: Drug-related problems (DRPs) are common in the elderly, leading to
      suboptimal therapy, hospitalisations and increased mortality. The integrated
      medicines management (IMM) model is a multifactorial interdisciplinary
      methodology aiming to optimise individual medication therapy throughout the
      hospital stay. IMM has been shown to reduce readmissions and drug-related
      hospital readmissions. Using the IMM model as a template, we have designed an
      intervention aiming both to improve medication safety in hospitals, and
      communication across the secondary and primary care interface. This paper
      presents the study protocol to explore the effects of the intervention with
      regard to healthcare use, health-related quality of life (HRQoL) and medication
      appropriateness in elderly patients. METHODS AND ANALYSIS: A total of 500
      patients aged >=70 years will be included and randomised to control (standard
      care) or intervention group (1:1). The intervention comprises five steps mainly
      performed by pharmacists: (1) medication reconciliation at admission, (2)
      medication review during hospital stay, (3) patient counselling about the use of
      medicines, (4) a comprehensible and patient-friendly medication list with
      explanations in discharge summary and (5) postdischarge phone calls to the
      primary care level. The primary outcome is the difference between intervention
      and control patients in the rate of emergency medical visits (acute readmissions
      and visits to emergency department) 12 months after discharge. Secondary outcomes
      include length of index hospital stay, time to first readmission, mortality, hip
      fractures, strokes, medication changes, HRQoL and medication appropriateness.
      Patient inclusion started in September 2016. ETHICS AND DISSEMINATION: The trial
      was approved by the Norwegian Centre for Research Data and the Norwegian Data
      Protection Authority. We aim to publish the results in international peer
      reviewed open access journals, at national and international conferences, and as
      part of two PhD theses. TRIAL REGISTRATION NUMBER: NCT02816086.

PMID- 29362277
TI  - Feeding amount significantly alters overt tumor onset rate in a zebrafish
      melanoma model.
AB  - The manner in which zebrafish are fed may have important impacts on the behavior
      of disease models. We examined the effect of different feeding regimens on the
      rate of overt melanoma tumor onset in a p53/BRAF-dependent model, a commonly used
      read-out in this and many other cancer models. We demonstrate that increased
      feeding leads to more rapid melanoma onset. The ability to modulate overt tumor
      onset rates with this regimen indicates additional flexibility to 'tune' the
      system to more quickly generate tumors for study and to begin to address
      questions related to cancer metabolism using the zebrafish model.

PMID- 29362278
TI  - Compensation for chronic oxidative stress in ALADIN null mice.
AB  - Mutations in the AAAS gene coding for the nuclear pore complex protein ALADIN
      lead to the autosomal recessive disorder triple A syndrome. Triple A patients
      present with a characteristic phenotype including alacrima, achalasia and adrenal
      insufficiency. Patient fibroblasts show increased levels of oxidative stress, and
      several in vitro studies have demonstrated that the nucleoporin ALADIN is
      involved in both the cellular oxidative stress response and adrenal
      steroidogenesis. It is known that ALADIN knock-out mice lack a phenotype
      resembling human triple A syndrome. The objective of this study was to determine
      whether the application of chronic oxidative stress by ingestion of paraquat
      would generate a triple A-like phenotype in ALADIN null mice. Adult male mice
      were fed either a paraquat (0.25 g/kg diet) or control diet for 11 days. After
      application of chronic oxidative stress, ALADIN knock-out mice presented with an
      unexpected compensated glutathione metabolism, but lacked a phenotype resembling
      human triple A syndrome. We did not observe increased levels of oxidative stress
      and alterations in adrenal steroidogenesis in mice depleted for ALADIN. This
      study stresses the species-specific role of the nucleoporin ALADIN, which in mice
      involves a novel compensatory mechanism for regulating the cellular glutathione
      redox response.

PMID- 29362279
TI  - [Surgical Technique for Lumbar Spinal Extraforaminal Schwannoma].
AB  - INTRODUCTION: Spinal neurinomas are frequently observed in the cauda equina,
      particularly within the dura mater. However, extraforaminal schwannomas(EFS),
      which are neither intradural nor dumbbell type, are relatively rare; hence,
      different surgical procedures have been employed. Here, we report 12 cases of
      lumbar EFS with total resection that were safely performed. METHODS AND SUBJECTS:
      This study was comprised of 12 patients with lumbar EFS(excluding those with
      neurofibromas)who were previously treated at our hospital. Using the Wiltse
      paraspinal approach, we inserted the microscope until it reached the tumor
      surface. After confirming the tumor surface, we inserted a scalpel to make an
      incision in a portion of the outer capsule. Then, we confirmed that the surfaces
      of the outer capsule and the tumor within the capsule could be dissected. Next, a
      thread was attached to the outer capsule and pulled upwards so that there was
      enough space to perform the required procedures within the capsule. Using a
      CUSA<sup>(r)</sup>, we removed the intracapsular tumor. After its removal, the
      outer capsule was treated carefully to ensure that the origin nerve was not
      damaged. RESULTS: In all cases, we successfully performed a total removal of the
      intracapsular tumor;in the mean postoperative observation period of 8 years, no
      recurrence was observed. Although temporary paralysis was observed in three
      patients, this improved over time. CONCLUSION: We report our experience with a
      surgical technique that ensured the safe removal of lumbar EFS. Satisfactory
      results were achieved, with no recurrences observed during the mean 8-year
      postoperative observation period.

PMID- 29362280
TI  - [Magnetic Resonance Imaging Conditions for Imaging of the Tarsal Tunnel].
AB  - BACKGROUND: Tarsal tunnel syndrome(TTS)is an entrapment neuropathy of the
      posterior tibial nerve within the tarsal tunnel below the medial malleolus. An
      accurate diagnosis is difficult, and TTS is usually diagnosed from clinical
      symptoms due to the lack of accurate diagnostic tools. We aimed to standardize
      the diagnosis of TTS using MRI, and report the MRI conditions for clear
      visualization of the tarsal tunnel. METHODS: We investigated which sequences and
      MRI conditions would be appropriate for the imaging of the tarsal tunnel in a
      healthy volunteer. As in routine brain MRI, the imaging time was within 15
      minutes. We also performed an MRI study of the tarsal tunnel in two patients with
      TTS. RESULTS: Axial images obtained by fat-suppression 3-dimensional
      T2<sup>*</sup>-weighted imaging(3D-T2<sup>*</sup>WI)are the most useful for
      visualization of the tarsal tunnel. The axial images obtained by T2-weighted
      imaging(T2WI)and T1-weighted imaging(T1WI)were also useful for visualization of
      the area around the flexor retinaculum. The appropriate slice thickness was
      determined to be 1.5 mm, based on the resolution and photographic time. The flip
      angle, necessary for tissue resolution, was set at 15 degrees  because it
      provided the clearest image and highest contrast between different tissues. The
      total photographic time was within 14 minutes, and it is acceptable for routine
      MRI studies of TTS. In the two cases of TTS included in this study, the tarsal
      tunnel was clearly visible. CONCLUSIONS: For diagnosis of TTS using MRI, axial
      images obtained by fat-suppression 3D-T2<sup>*</sup>WI, 2-dimensional(2D)-T2WI,
      and 2D-T1WI are recommended. A coronal image obtained by reconstruction of fat
      suppression 3D-T2<sup>*</sup>WI might be useful for anatomical understanding. In
      future studies, we plan to evaluate patients with TTS using the above protocol.

PMID- 29362281
TI  - [Takotsubo Cardiomyopathy and Neurogenic Pulmonary Edema Following Fibrinolytic
      Therapy for Embolic Stroke:A Case Report].
AB  - A 79-year-old man presented with left hemiparesis and disturbance of
      consciousness. Brain magnetic resonance(MR)imaging revealed an infarction in the
      right insular cortex. MR angiography showed a defect in the inferior trunk of the
      right middle cerebral artery. The patient was treated with alteplase about 2.5 h
      after onset. Immediately after the intravenous alteplase administration, the
      hemiparesis improved. However, his respiratory condition unexpectedly worsened 10
      h after onset. Chest radiography demonstrated an infiltrative shadow in both lung
      fields. Transthoracic echocardiogram showed a dysfunction in the left ventricle
      and no contraction at the apex of the heart, consistent with a type of
      cardiomyopathy, known as takotsubo cardiomyopathy(TCM). Gradually, the patient's
      respiratory and cardiac function improved. Here, we describe a very rare case of
      TCM and neurogenic pulmonary edema(NPE)following an acute cerebral infarction,
      which was treated with alteplase intravenous administration. TCM and NPE have a
      poor prognosis, therefore diagnosis, management, and treatment in the acute phase
      is required.

PMID- 29362282
TI  - [A Ruptured Middle Cerebral Artery Dissecting Aneurysm Operation in a 2-Year-Old
      Boy].
AB  - We report the case of a ruptured dissecting aneurysm in an infant. A 2-year-old
      boy suffered sudden headache and nausea. CT scan revealed a subarachnoid
      hemorrhage, and digital subtraction angiography(DSA)revealed a dissecting
      aneurysm(3.9mm)at a branch of the right middle cerebral artery(MCA). Eight days
      after onset, carotid angiography revealed enlargement of the aneurysm(up to 6.8
      mm). Right frontotemporal craniotomy and aneurysm trapping with STA-MCA bypass
      was performed. Two years and two months later, the aneurysm recurred as assessed
      by magnetic resonance angiography(MRA). DSA revealed the recurrence of the
      aneurysm(7.8mm)proximal to the previous aneurysm and displayed development of
      collateral flow through leptomeningeal anastomosis between the branches of the
      MCA. During the second operation, the aneurysm extended to the artery branch
      proximal to the previous trapping. Parent artery occlusion without bypass was
      performed. Postoperative DSA revealed collateral flows through leptomeningeal
      anastomosis between the branch of the MCA and the branch of anterior cerebral
      artery. At the 3-year follow-up period, abnormal findings on MRI did not appear
      and he was healthy without any neurologic abnormalities.

PMID- 29362283
TI  - [A Case of Primary Intracranial Epithelioid Hemangioendothelioma].
AB  - Epithelioid hemangioendotheliomas(EHEs)most commonly occur in the liver, lung,
      bone, and soft tissues, but rarely in the brain. Here, we describe a case of
      primary intracranial epithelioid hemangioendothelioma manifested by an epileptic
      attack. A 53-year-old woman with no previous convulsive history presented at our
      hospital after experiencing a seizure. Magnetic resonance imaging revealed a mass
      in her right frontal lobe, with edema, which was well enhanced with gadolinium.
      Systemic computed tomography, on the other hand, did not show any tumor
      involvement in other organs. The patient underwent surgery, and a complete
      resection of the intracranial tumor was successfully performed. The histological
      diagnosis was an EHE. There was no evidence of tumor recurrence either in the
      brain or other organs at 3 years and 7 months after surgery. Because of its
      rarity, the exact prognosis of patients with an intracranial EHE has not been
      clearly established. Moreover, tumor recurrence following complete resection has
      been reported and thus regular follow-up examinations are considered necessary.

PMID- 29362284
TI  - [Endarterectomy for Internal Carotid Artery Occlusion, with an Aberrant Branch of
      the Internal Carotid Artery Maintaining Blood Flow Distal to the Complete
      Occlusion:A Case Report].
AB  - Doppler sonography accurately identifies occlusion of the internal carotid
      artery(ICA)and current surgical guidelines do not list an occluded ICA as an
      indication for carotid endarterectomy(CEA). We encountered an unusual case, for
      which we performed CEA. The left ICA was occluded by atherosclerosis, and was
      reconstituted via an aberrant branch of the occipital artery. A 71-year-old man
      was referred following brain infarction. Carotid duplex
      sonography(CDS)demonstrated occlusion of his left ICA, with flow in the distal
      ICA beyond the occlusion("Sandwich stump sign"). 3D computed tomography
      angiography and cervical angiography diagnosed ICA occlusion with flow in the
      distal ICA, and the patient underwent CEA. Careful evaluation is required when
      apparent occlusion of the ICA is detected to avoid overlooking a flow pattern
      beyond the occlusion and to determine whether repair is possible.

PMID- 29362285
TI  - [Rapid Recanalization of Cerebral Venous Sinus Thrombosis Secondary to Severe
      Dehydration:A Case Report].
AB  - A 41-year-old healthy man presented with sudden disturbance of consciousness and
      convulsion during a marathon. Computed tomography revealed a lateral sinus sign
      in the posterior fossa, and magnetic resonance(MR)venography revealed a flow gap
      in the posterior part of the superior sagittal sinus and bilateral transverse
      sinus, although the other MR image sequences were normal. Laboratory data
      revealed dehydration, acute kidney failure, and rhabdomyolysis. Owing to
      immediate correction of dehydration, clinical symptoms and radiological
      abnormality improved rapidly. Cerebral venous sinus thrombosis(CVST)is a rare
      condition, accounting for <1% of all stroke cases. In all cases, CVST cannot
      cause cerebral infarction or hemorrhagic change but in any case, may present a
      transient ischemic attack-like event because of rapid spontaneous recanalization.
      Therefore, CVST may occur more frequently than expected.

PMID- 29362286
TI  - [Bilateral Internal Carotid Artery Dissection Caused by Elongated Styloid
      Processes:A Case Report].
AB  - We report a case of bilateral internal carotid artery(ICA)dissection associated
      with bilateral elongated styloid processes(ESPs). A 46-year-old man presented
      with transient aphasia and left visual disturbance at a business meeting. He
      complained of a foreign body sensation in his throat during swallowing for two
      years. Magnetic resonance imaging(MRI)demonstrated fresh small infarcts in the
      left corona radiata. Magnetic resonance angiography(MRA)revealed string signs
      bilaterally in the cervical ICAs. The patient was diagnosed with bilateral
      idiopathic ICA dissection and was treated with ozagrel and clopidogrel. Three
      dimensional computed tomographic angiogram(3DCTA)indicated bilateral ESPs and
      bilateral ICA stenosis. 3DCTA with the patient's head tilting and neck extension
      revealed that each ICA was compressed by the ipsilateral ESP. A follow-up MRA
      showed complete normalization of bilateral ICAs after neck rest and anti-platelet
      therapy, following which, clopidogrel was stopped. The patient wore a soft
      cervical collar until the operation, to avoid contact between the ESPs and ICAs
      due to changes in head position. Bilateral ESP resection was performed to prevent
      recurrence of cerebral ischemic events caused by ICA dissection. The patient was
      discharged one week after the surgery without any neurological deficit. There was
      no recurrence of symptoms during the next eight months after the operation.

PMID- 29362287
TI  - [A Case of Traumatic Occipital Artery Pseudoaneurysm Followed by Hemorrhagic
      Shock].

PMID- 29362288
TI  - [(1)Detection of Epileptic Focus Using Electroencephalography-Functional Magnetic
      Resonance Imaging(EEG-fMRI)].

PMID- 29362289
TI  - Cross-organelle communication at the core of longevity.

PMID- 29362290
TI  - The neuronal Shc adaptor in Alzheimer's Disease.

PMID- 29362291
TI  - Stem cell depletion by inflammation-associated miR-155.

PMID- 29362292
TI  - High-performance electrochemical glucose sensing enabled by Cu(TCNQ) nanorod
      array.
AB  - It is highly attractive to construct stable enzyme-free glucose sensors based on
      three-dimensional direct electrochemical detection of glucose. In this paper, a
      copper 7,7,8,8-tetracyanoquinodimethane (Cu(TCNQ)) nanorod array on Cu foam
      (Cu(TCNQ) NA/CF) is proposed as an efficient catalyst for electrochemical glucose
      oxidation in alkaline conditions. When Cu(TCNQ) NA/CF was used as the enzyme-free
      sensory of glucose, the sensor showed a response time within 3 s, a wide linear
      detection in the range 0.001-10.0 mM, the minimum limit of detection was as low
      as 10 nM (S/N = 3), and it had a high sensitivity of 26 987 MUA mM-1 cm-2.
      Moreover, this sensor also possesses long-term stability, high selectivity,
      reproducibility, and actual applications for fresh human serum sample analysis is
      also successfully accepted.

PMID- 29362293
TI  - Self-neutralizing PLGA/magnesium composites as novel biomaterials for tissue
      engineering.
AB  - Controlling acidic degradation of biodegradable polyesters remains a major
      clinical challenge. This work presents a simple and effective strategy of
      developing polyester composites with biodegradable magnesium metal or alloys.
      PLGA samples with compositions of 1, 3, 5, and 10 wt% magnesium were produced
      using a simple solvent-casting method, which resulted in composite films with
      near uniform Mg metal/alloy particle dispersion. Degradation study of the
      composite films showed that all compositions higher than 1 wt% magnesium were
      able to extend the duration of degradation, and buffer acidic pH resulting from
      PLGA degradation. PLGA composite with 5 wt% of magnesium showed near-neutral
      degradation pattern under sink conditions. Magnesium addition also showed
      improved mechanical characteristics in terms of the tensile modulus. In vitro
      experiments conducted by seeding PLGA composites with MC3T3-E1 pre-osteoblasts
      demonstrated increased ALP expression and cellular mineralization. The
      established new biodegradable polymer-metal system provides a useful biomaterial
      platform with a wide range of applications in biomedical device development and
      scaffold-based tissue engineering.

PMID- 29362294
TI  - Prevalence of sleep quality disorder among Iranian drivers: a systematic review
      and meta-analysis.
AB  - BACKGROUND: Sleep Quality Disorder (SQD) plays a major role in road accidents.
      So, this study was carried out to determine the prevalence of SQD among
      occupational drivers using systematic review and meta-analysis in Iran. METHODS:
      All Persian and English articles between January, 2000 and October, 2015 which
      had reported the SQD prevalence in Iranian drivers by Pittsburgh Sleep Quality
      Index (PSQI) with cross-sectional design, after the quality evaluation process
      and achieving the required score were selected. The heterogenic index of the
      studies was distinguished by using Cochran (Q) and I2 tests. Based on
      heterogeneity results, a random effects model was used to estimate pooled
      prevalence of SQD. Meta-regression was also used to investigate the heterogeneity
      of suspected factors. RESULTS: In total, 936 articles were found from national
      and international databases. Ten articles entered to meta-analysis process,
      ultimately. Since heterogeneity index suggested that there is a considerable
      heterogeneity among the results of primary studies (I-squared = 98.8%, Q= 754.1,
      p less than 0.001), the overall estimation of SQD among Iranian drivers was
      conducted using random-effects model and its rate was estimated to be 53.4% (95%
      CI: 38.9-67.8). CONCLUSIONS: Our study demonstrated that more than half of
      Iranian drivers have SQD. Identifying the drivers with SQD by periodic
      examinations and providing advice and health care among occupational drivers
      could be appropriate solutions for decreasing the accident risks.

PMID- 29362296
TI  - [Epigenetic Alterations in Gastrointestinal Cancers: Diagnostic and Therapeutic
      Applications].
AB  - Epigenetic alterations, represented byaberrant DNA methylation, are present in
      gastrointestinal cancers. Detection of cancer- specific DNA methylation can be
      used to detect cancer, and detection of colon cancer-specific aberrant DNA
      methylation is alreadyapproved byFDA. Aberrant DNA methylation is potentlyinduced
      bychronic inflammation, and also is accumulated in normal tissues before a cancer
      develops. In gastric cancer, potential of cancer risk diagnosis bymeasurement of
      aberrant DNA methylation in normal gastric mucosae has been clinically
      demonstrated. Therapeutically, DNA demethylating agents have been alreadyapproved
      for hematological tumors byFDA, and promising results in clinical trials against
      gastrointestinal cancers have been reported. Also, histone deacetylase inhibitors
      have been already approved for hematological tumors, and clinical trials against
      gastrointestinal cancers have been reported. Selection of right dose, schedule,
      combination, and patients is the keyto future success.

PMID- 29362295
TI  - Epidemiology and history of knee injury and its impact on activity limitation
      among football premier league professional referees.
AB  - BACKGROUND: The purpose of this study was to determine the epidemiology and
      history of knee injury and its impact on activity limitation among football
      premier league professional referees in Iran. METHODS: This was a descriptive
      study. 59 Football Premier League professional referees participated in the
      study. The knee injury related information such as injury history and mechanism
      was recorded. Injury related symptoms and their impacts on the activity
      limitation, ability to perform activities of daily living as well participation
      in sports and recreational activities was obtained through the Knee Outcome
      Survey (KOS). RESULTS: The results indicated that 31 out of 59 participants
      reported the history of knee injury. In addition, 18.6%, 22.4% and 81% of the
      referees reported that they had been injured during the last 6 months of the last
      year, and at some point in their refereeing careers, respectively. Results
      further indicated that 48.8% of the injuries occurred in the non-dominant leg and
      they occurred more frequently during training sessions (52%). Furthermore, the
      value of KOS was 85 +/- 13 for Activities of Daily Living subscale and 90 +/- 9
      for Sports and Recreational Activities subscale of the KOS. CONCLUSIONS: Knee
      injury was quite common among the Football Premier League professional referees.
      It was also indicated that the injuries occurred mainly due to insufficient
      physical fitness. Therefore, it is suggested that football referees undergo the
      proper warm-up program to avoid knee injury.

PMID- 29362297
TI  - [The Risk Factors of Cancer Chemotherapy in Elderly Patients].
AB  - The aging rate in Japan is the highest in the world, and it is entering a very
      aging society that has never happened before. The first cause of death is a
      malignant neoplasm, and opportunities of the treatment for elderly cancer
      patients are rapidly increasing. The elderly have increased chronic diseases and
      complications with aging, and the adverse event in medication therapy also
      increases. Also, the form of medical provision is diversified, home medical care
      and nursing care are recommended. Therefore, it is important to appreciate the
      various aspects including psychophysiological, living, social aspects in addition
      to changes in physical function caused by aging and appropriately evaluate them,
      for selecting treatment methods in elderly cancer patients. Geriatric
      assessment(GA)is recommended for this evaluation, and it is expected to
      contribute to improvement of treatment outcome and quality of life(QOL). In this
      article, we will outline the role of aged general comprehensive functional
      evaluation in elderly cancer treatment and the problems of chemotherapy in the
      elderly.

PMID- 29362298
TI  - [Risk Assessment of Chemotherapy for the Elderly Patients with Gastrointestinal
      Cancer].
AB  - The basic principles in the chemotherapeutic treatment of elderly colorectal
      cancer patients are similar to those of young people, but because of age-related
      organ function deterioration and comorbidities that are involved in life
      prognosis, there are risks of side effects in drug therapy. Considering the
      influence on the quality of life(QOL)is necessary. In the treatment guidelines,
      recommended initial chemotherapeutic options for unresectable colorectal cancer
      depends on whether the patient is appropriate for intensive therapy, but there
      are no criteria on how to divide. International Society of Geriatric Oncology
      (SIOG)recommend screening tool, i. e. G8, is recommended to identify those
      patients in need of comprehensive geriatric assessment(CGA). If abnormal,
      screening should be followed by CGA. Further researches are ongoing to build
      clinical pathways using screening tool and CGA.

PMID- 29362299
TI  - [Risk Assessment of Hematologic Malignancy Treatment of the Elderly].
AB  - Along with the aging society in Japan, the number ofelderly cancer patients is
      increasing, and hematological malignancy is no exception. Treatment
      ofhematological malignancy is mainly chemotherapy and furthermore it is necessary
      to keep its dose intensity. In the elderly, adverse events may be strong due to
      deterioration oforgan function, comorbidity, etc., and it is difficult for
      individual differences to decide chemotherapy regimen and dose. Geriatric
      assessment(GA)used in the field of geriatric medicine is reported to be useful
      for risk assessment of chemotherapy. The usefulness of GA is also shown in
      hematological malignancy. In non-Hodgkin's lymphoma, attempts have been made to
      determine the treatment method by stratifying the risk using the results of GA.

PMID- 29362300
TI  - [Prognostic Value of Geriatric Screening Tools in Elderly Cancer Patients].
AB  - The elderly population is heterogeneous. Chronological age alone does not reflect
      heterogeneity in the aging process. It is recommended that elderly cancer
      patients should be evaluated for some form of geriatric assessment(GA)to detect
      problems, to predict treatment-related toxicities, to predict functional decline,
      to predict prognosis, and to assist in cancer treatment decisions. It was
      reported that functional status, nutritional status, mental status, polypharmacy,
      and comorbidity were independent prognostic factors for survival in elderly
      cancer patients. Although a full GA is valuable, it is time-consuming. Therefore,
      in a busy practice, geriatric screening tools are useful to identify patients in
      need of further evaluation using a full GA. Assessment for screening tools takes
      a few minutes. Some screening tools such as Geriatric 8(G8), Vulnerable Elders
      Survey-13(VES-13), Groningen Frailty Indicator(GFI), and Flemish version of the
      Triage Risk Screening Tool(fTRST)have prognostic value for survival. These
      screening tools may help physicians make informed treatment decisions in daily
      practice.

PMID- 29362301
TI  - [Genitourinary Tumor Four Questions about Bladder Cancer].

PMID- 29362302
TI  - [I .Recent Trends in Bladder Cancer Mortality in Japan].

PMID- 29362303
TI  - [II .Problems of Treatment for Non-Muscle Invasive Bladder Cancer].

PMID- 29362304
TI  - [III .Current Status of Bladder Preservation Therapy for Muscle Invasive Bladder
      Cancer].

PMID- 29362305
TI  - [IV .The Role of Immune Checkpoint Blockade in the Treatment of Bladder Cancer].

PMID- 29362306
TI  - [Evaluation of Chemotherapy-Induced Nausea and Vomiting in Patients with
      Hematological Malignancies Using MASCC Antiemesis Tool(MAT)].
AB  - Chemotherapy-induced nausea and vomiting(CINV)were prospectively evaluated using
      MASCC Antiemesis Tool(MAT) in patients with hematological malignancies in our
      institution. A total of 33 patients receiving 46 chemotherapy courses were
      evaluated. Although vomiting was not observed in the acute phase, nausea was seen
      in 22.6% and 32.3% of the patients in the acute and delayed phases, respectively.
      Thirty percent(25 cases)of the patients receiving highly emetogenic chemotherapy
      presented nausea in both the phases, while 40%(18 cases)of the patients receiving
      moderately emetogenic chemotherapy presented nausea in the delayed phase. The
      oral intake was quantitated retrospectively in 31 patients with non- Hodgkin's
      lymphoma, who were hospitalized and received CHOP+/-R. Prior to the initiation of
      the chemotherapy, 13 patients received the first generation 5-HT3 receptor
      antagonist granisetron, while 18 patients received the second generation
      palonosetron. Oral intake was greater in the patients who were administered
      palonosetron. Thus, the present study suggested that antiemetic treatment could
      be improved at our institution.

PMID- 29362307
TI  - [A Case of Fatal Interstitial Pneumonia during FOLFIRI plus Cetuximab Therapy for
      Liver Metastasis of Colon Cancer].
AB  - The patient was a 76-year-old woman who underwent sigmoidectomy in April 2011 for
      sigmoid colon cancer with multiple concurrent liver metastases. She was treated
      postoperatively with mFOLFOX6 plus cetuximab but was diagnosed with the
      progressive disease at the end of course 14. The patient started receiving
      FOLFIRI plus cetuximab therapy in May 2012. Later in August 2012, she was
      examined for respiratory distress on the scheduled date of receiving course 7 and
      was diagnosed with drug-induced interstitial pneumonia resulting from systemic
      chemotherapy. The patient was administered oxygen, and her symptoms improved
      temporarily with steroid half-pulse and endotoxin adsorption therapy, but on
      inpatient day 10, her respiratory condition deteriorated. She was treated with
      steroid pulse therapy, but died of respiratory failure on inpatient day 17. The
      main adverse events associated with FOLFIRI plus cetuximab therapy are
      gastrointestinal symptoms, hematotoxicity, peripheral nerve damage, and
      dermatological symptoms. However, reports of respiratory conditions such as
      interstitial pneumonia are rare. Although the incidence is low, interstitial
      pneumonia can be severe and fatal and therefore requires close attention.

PMID- 29362308
TI  - [An Elderly Patient with Metastatic Colon Cancer Achieved Long-Term Survival
      Following Single-Agent Chemotherapy with S-1].
AB  - Colorectal cancer is a common malignancy and a major health issue in geriatrics.
      Systemic chemotherapy should be considered for elderly patients. We report an 85
      year-old man with metastatic cecal cancer who has achieved long-term survival
      following single-agent chemotherapy with S-1. His fecal occult blood test results
      were positive; he then underwent colonoscopy and was diagnosed with cecal cancer.
      Chest CT revealed multiple metastases in both lungs. Since radical excision was
      infeasible, we performed right hemicolectomy to prevent bowel obstruction.
      Histological examination revealed a T3, N0, M1a (PUL2), Stage IV tumor. After
      discharge from the hospital, the patient preferred receiving chemotherapy that
      would have fewer side effects. S-1 monotherapy was administered. Despite
      increased progression of the pulmonary metastases, he experienced no subjective
      symptoms, his QOL remained consistent, and he completed 42 cycles of chemotherapy
      in total. The patient is currently being managed on an outpatient basis. In
      conclusion, elderly patients with cancer should be carefully evaluated according
      to both disease control and individual circumstances, such as patient's
      tolerability, QOL, and preference.

PMID- 29362309
TI  - [A Case Report of Sigmoid Colon Cancer with Multiple Lung Metastases Successfully
      Treated with S-1].
AB  - A patient in his 70s was diagnosed with sigmoid colon cancer[pT3pN1cM1(PUL1),
      pStage IV ]for which he underwent sigmoid colectomy and received S-1 adjuvant
      therapy for the lung metastases. The patient received a total of 10 courses of S-
      1, administered orally on days 1-14 of a 21-day cycle. The lung metastases showed
      a complete response, and the patient completed the S-1 chemotherapy. No
      recurrence of lung metastases was detected up to 6 months later.

PMID- 29362310
TI  - [A Case of Anal Canal Squamous Cell Carcinoma Detected with Anal Stenosis Eight
      Years Following Resection for Rectal Adenocarcinoma].
AB  - An 89-year-old woman underwent low anterior resection for rectal
      adenocarcinoma(Ra, pT3N0M0, pStage II , Cur A)in 2008. In February 2016, she
      underwent an outpatient examination because of a defecation disturbance. Lower
      gastrointestinal endoscopy was performed and the stenotic region was biopsied.
      However, no malignancy was detected and the stenotic site expanded. However, the
      patient experienced recurrence of the same symptoms, developed severe anal
      stenosis, and underwent another examination in December 2016. Magnetic resonance
      imaging indicated a neoplastic lesion around the entire circumference of the anal
      canal. Transperineal needle biopsy results indicated squamous cell carcinoma. The
      patient was diagnosed with postoperative rectal cancer and metachronous anal
      canal squamous cell carcinoma(P, cT4bN2M0, cStage III b). Laparoscopic artificial
      anus construction was performed with the aim of unblocking the anal canal
      stenosis. Considering the patient's age and performance status, radiation therapy
      was administered. Two months after administering radiation therapy, the tumor
      decreased in size, and anal pain reduced.

PMID- 29362311
TI  - [Three Cases of Advanced or Recurrent Adrenocortical Carcinoma Patients Treated
      with Etoposide, Doxorubicin and Cisplatin plus Mitotane].
AB  - Adrenocortical carcinoma is a rare cancer with poor clinical outcomes due to its
      propensity to transform or relapse. Reported here are 3 cases of adrenocortical
      carcinoma that were treated between January 2007a nd December 2013. Etoposide,
      doxorubicin, and cisplatin plus mitotane(EDP plus mitotane)were administered as
      adjuvant therapy to 1 patient, while the other patients received the therapy upon
      relapse of their cancers following surgery. One patient experienced PR and
      another 1 experienced SD during the course of their treatment. While 2 of the
      patients experienced Grade 3 non-hematological adverse events, all of them
      experienced Grade 3/4 hematological adverse events. The FIRM-ACT study reported
      in 2012, proved the effectiveness of EDP plus mitotane for advanced
      adrenocortical carcinoma, in spite of the several adverse events it caused. Some
      of the adverse events were severe, resulting in a poor quality of life in the
      patients. There is not enough evidence to support the use of EDP plus mitotane
      postoperatively or in recurrent patients. Moreover, due to the rare nature of
      adrenocortical carcinomas, we don't have enough management cases of EDP plus
      mitotane chemotherapy for dominant patients. More cases need to be studied to
      collect sufficient data on the benefits of EDP plus mitotane therapy for adjuvant
      or relapsed adrenocortical carcinoma.

PMID- 29362312
TI  - [Synchronous and Unilateral Breast Cancers(Invasive Lobular Carcinoma and Non
      Invasive Ductal Carcinoma) - A Case Report].
AB  - We report a case of synchronous and unilateral breast cancers in a 51-year-old
      female.A focal asymmetric right breast density was detected on breast cancer
      screening mammography.Ultrasonography showed a low echoic mass, 9mm in diameter,
      in the B area, and a second low echoic mass in the CD area of her right breast.A
      core needle biopsy of the B area mass led to a diagnosis of an invasive lobular
      carcinoma, positive for estrogen receptor(ER)and progesterone receptor(PgR), and
      negative for HER2/neu.One -percent of the tumor cells were Ki-67 positive.Her
      preoperative diagnosis was Stage I (T1N0M0).She underwent muscle-preserving
      mastectomy plus sentinel lymph node biopsy.The pathological diagnosis from the
      resected surgical specimen was invasive lobular carcinoma(B area), positive for
      ER, and negative for PgR and HER2/neu protein expression.From this, she was
      additionally diagnosed with non-invasive ductal carcinoma(CD area)that was posi-
      tive for ER, and negative for PgR and HER2/neu protein expression.The surgical
      margins were negative, and there were no sentinel lymph node metastases.These
      tumors were independent.She was given adjuvant endocrine therapy.Two years and 6
      months after surgery, the patient was doing well and without metastases.

PMID- 29362313
TI  - [Long-Term Effect of Fulvestrant for Locally Advanced Breast Cancer in an Elderly
      Patient - A Case Report].
AB  - We report an elderly patient with locally advanced breast cancer who received
      long-term fulvestrant therapy.The patient was a 75-year-old woman who presented
      with a right breast lump.She noticed the tumor 4 years and 6 months ago, but she
      had not visited any hospital.However, her daughter brought her to our
      hospital.The tumor was 73mm in diameter.A core needle biopsy for breast tumor led
      to a diagnosis of an invasive ductal carcinoma, positive for estrogen
      receptor(ER)and progesterone receptor(PgR), and negative for HER2/neu.The Ki-67
      positive cell index was 20%.We performed a whole- body checkup, and confirmed the
      diagnosis as T4cN1M0, Stage III B.She initiated endocrine therapy by
      letrozole(2.5 mg/ day).After 1 year and 6months, tumor marker levels increased.We
      changed the endocrine therapy to fulvestrant(500mg/ month).For the next 2 years
      and 6 months, this therapy was effective.Her axillary lymph node metastases
      disappeared and tumor size decreased(60%).She underwent muscle-preserving
      mastectomy plus axillary lymph node dissection.The pathological diagnosis from
      the resected surgical specimen was confirmed as invasive ductal carcinoma,
      positive for ER and PgR, and negative for HER2/neu protein expression.The
      surgical margins were negative, and there was no metastasis in the lymph
      nodes.She was administered adjuvant endocrine therapy.Four years after surgery,
      she was well without metastasis.

PMID- 29362314
TI  - [The Clinical Effect of Ramucirumab in the Treatment of Advanced Gastric Cancer
      in Our Hospital].
AB  - Ramucirumab(RAM)was approved for unresectable advanced gastric cancer in March
      2015. Recent Japanese gastric cancer treatment guidelines recommended RAM plus
      paclitaxel(PTX)and RAM alone in the treatment of patients with advanced gastric
      cancer who had been previously treated with chemotherapy. In this retrospective
      study, we evaluated the safety and efficacy of RAM alone and PTX plus RAM in
      these patients. Patients who were administered RAM or PTX plus RAM between March
      2015 and December 2016 were enrolled in this study. We compared the clinical
      outcome of RAM alone(RAM group, n=11)with that of PTX plus RAM(PTX plus RAM
      group, n=10). The RAM group contained more patients with poor performance status
      than the PTX plus RAM group. More cases of Grade 3 or 4 adverse events were found
      in the PTX plus RAM group than in the RAM group. The response rate was 9% in the
      RAM group and 30% in the PTX plus RAM group. The progression-free survival was 2
      months in the RAM group and 3.75 months in the PTX plus RAM group. The overall
      survival was not reached in the RAM and PTX plus RAM groups. We considered that
      RAM and PTX plus RAM are safe and effective therapies for advanced gastric cancer
      patients.

PMID- 29362315
TI  - [A Case of Port Site Recurrence of Gallbladder Carcinoma after Laparoscopic
      Cholecystectomy].
AB  - The patient was a 76-year-old man who underwent laparoscopic cholecystectomy with
      a diagnosis of cholecystolithiasis. Since the definite diagnosis of gallbladder
      carcinoma was made after the operation, he underwent additional resection. Four
      years later, he revisited the hospital complaining of painful swelling of the
      port site of his epigastrium. Magnetic resonance imaging of the abdomen revealed
      a mass 3.4 cm in diameter at the epigastrium. Thus, port site recurrence of
      gallbladder carcinoma was the suspected diagnosis. We resected the peritoneum,
      rectus abdominis muscle, and skin, as well as the tumor, and the abdominal wall
      was reconstructed using synthetic composite mesh. Histological examinations
      revealed recurrence of gallbladder carcinoma. Port site recurrence of gallbladder
      carcinoma is known to have a poor prognosis, but long survival can be expected in
      patients after complete resection of the metastatic lesion, if the recurrence
      develops more than a year after the initial operation.

PMID- 29362316
TI  - [Gallbladder Malignant Lymphoma Diagnosed after Surgery for Acute Cholecystitis -
      A Case Report].
AB  - An 84-year-old man visited our hospital with epigastralgia.Levels of hepatic and
      biliary enzymes and CRP were elevated, as detected by a blood test.On a CT scan,
      a swollen gallbladder with stones was detected.The patient was admitted to the
      hospital with a diagnosis of Grade I acute cholecystitis.Conservative treatment
      was continued with antibiotic administration and the patient was discharged from
      the hospital with improvement on day 6 after admission.Three months later, the
      patient underwent laparoscopic cholecystectomy.In the gallbladder, a 45*45 mm
      tumor was found.Upon pathological examination, diffuse proliferation of
      lymphocyte-like heterotypic cells and subserosal invasion were
      observed.Immunohistochemistry results were negative for MUM1 and positive for
      CD10 and Bcl6 markers.A malignant diffuse large B-cell lymphoma was diagnosed.We
      experienced a case of malignant lymphoma of the gallbladder diagnosed after
      surgery for acute cholecystitis, which we herein report with literature
      consideration.

PMID- 29362317
TI  - [A Resectable Case of TS-1 Therapy Useful in Distinguishing Primary Lung Cancer
      from Lung Metastases of Pancreatic Cancer].
AB  - We report a case of pneumonectomy followed by radical pancreatectomy after oral
      administration of TS-1 for pancreatic cancer with complications ofa lung tumor.
      The patient was a 66-year-old woman. A pancreatic tail tumor and 2 lung nodules
      were detected on CT scans, and were diagnosed as pancreatic cancer and metastatic
      lung cancer. During a total of1 1 courses ofTS -1 therapy, the pancreatic tumor
      tended to contract, but both pulmonary nodules remained unchanged. Due to
      differences in treatment effect, double cancers of the lung and pancreas were
      suspected, rather than metastatic lung cancers. We performed a VATS partial
      resection of the left lower lobe for diagnostic therapy. The pathological
      diagnosis revealed an inflammatory myofibroblastic tumor and a primary lung
      cancer. We diagnosed that a radical pancreatectomy was possible and performed
      distal pancreatectomy. Pathological diagnosis confirmed an invasive pancreatic
      ductal carcinoma. Oral administration ofTS -1 was performed as adjuvant
      chemotherapy after surgery. Liver metastasis was observed 10 months after
      pancreatectomy, and GEM therapy was initiated. Peritoneal dissemination was
      observed at 2 years following pancreatectomy, and the patient died at 2 years and
      9 months. TS-1 therapy for synchronous lung tumors and pancreatic cancer with
      careful observation allowed for a definitive radical resection. This method was
      an effective treatment for lung nodules with pancreatic cancer.

PMID- 29362318
TI  - [Azygos Arch Preserving Thoracoscopic Esophagectomy for Less Invasiveness].
AB  - We reported the technique ofthoracoscopic esophagectomy with preservation
      ofazygos arch for less invasivenesss. Among thoracoscopic esophagectomy, this
      retchnique indicated for the patients with the tumor located at middle or lower
      thoracic and don't reach adventitia. Twenty-eight patients was performed this
      procedure and azygos arch were preserved in all cases. None the cases were
      converted conventional thoracotomy. The operation time was 133.5 minutes(median),
      and estimated blood loss was 30 mL(median)in thoracic procedure. As for
      thoracoscopic esophagectomy, could preserved respiratory function, further less
      surgical stress can obtain this technique.

PMID- 29362319
TI  - [Long-Term Capecitabine Therapy Was Successful for Locally Advanced Breast Cancer
      Patient - Report of a Case].
AB  - For the treatment of locally advanced breast cancer, chemotherapy involving
      anthracycline and/or taxane-containg regimens is generally performed. However,
      some patients have difficult reasons for administering these intravenous
      chemotherapeutic agents. We experienced a case of locally advanced breast cancer
      patient who received long-term capecitabine therapy. This therapy was effective
      for this patient. A 72 year-old woman presented with a lump in her right breast.
      The tumor had been increasing for 15 years. The tumor had spread from the right
      breast to the axilla and the lateral chest, accompanied with ulceration. A core
      needle biopsy was performed and the pathological diagnosis was papillotubular
      carcinoma. We checked up her body, and there was no distant metastasis. We
      diagnosed the clinical stage as T4cN3aM0, stage III C. She was concerned about
      the side effect of depilation and did not wish the standard chemotherapy. We
      chose capecitabine therapy. She continued capecitabine therapy and endocrine
      therapy. The tumor and tumor markers were decreased. The tumor size has not
      increased and metastatic lesions have not appeared for 5 years and a half.

PMID- 29362320
TI  - [The Efficacy of Definitive Chemoradiotherapy for Thoracic Esophageal Cancer on
      the Point of View Salvage Surgery].
AB  - INTRODUCTION: Salvage surgery(S-surgery)was performed for residual or relapse
      tumor after definitive chemoradiotherapy (dCRT)for resectable esophageal cancer.
      When it becomes possible to perform surgery after dCRT for unresectable cases is
      called conversion surgery(C-surgery). OBJECTIVE: To examine the outcomes of S
      surgery and C-surgery after dCRT for thoracic esophageal cancer and clarify the
      significance as a multidisciplinary treatment. MATERIAL AND METHODS: We reviewed
      27 patients who underwent S-surgery for thoracic esophageal cancer in our
      hospital. 23 cases were residual tumor, 4 were relapse after complete response.
      Sixteen cases(59%)were C-surgery. RESULTS: Five cases(19%)had non-radical
      resection. Two cases were postoperative hospital death(7%). Postoperative
      complications(Clavien-Dindo classification Grade II and more) 11 cases(41%). Four
      cases were anastomotic leakage, 4 cases vocal cord paralysis, etc. Pathological
      complete response cases 6 cases(22%). The recurrence cases were 7 except for 5
      cases of non-radical resection. Three-year overall survival rate was 47%. Twelve
      cases(75%)in C-surgery could perform radical resection by down stage.
      CONCLUSIONS: The postoperative hospital mortality and complications can be
      considered as acceptable. dCRT is a powerful pre-operative treatment for such
      cases, and S-surgery plays an important role.

PMID- 29362321
TI  - [Multiple Resections for Metastases from Colorectal Cancer].
AB  - PURPOSE: We analyzed to clarify an outcome of multiple resections of metastases
      from colorectal cancer. PATIENTS AND METHOD: Total 7 cases who underwent several
      resections for metastases from colorectal cancer in Saiseikai Kurihashi Hospital
      after 2010 were enrolled for analysis. RESULT: Age of patients at the time of the
      primary site resection was 67(45-78)year-old, including 4males and 3 females.
      Patients located at cecum/ascending/sigmoid/rectosigmoid/upper rectum were
      1/1/2/2/1 respectively. Metachronous metastases were found in 5 patients. There
      were 1 patient for Stage I , 2 patients for Stage III a and III b each and all
      Stage III patients received adjuvant chemotherapy. The resected organs were 9 in
      lung, 8 in liver, 1 case in lymph node, local site and peritoneum and the median
      resected sites were 3(2-4)lesions. In 17 months median observation periods after
      latest resection, 5 cases have not been prolapsed including 3 cases with
      chemotherapy. Two cases were relapsed with unresectble status. One case died for
      24 months and one case is under the chemotherapy for 12 months. Five year
      survival rate was 75% and 2 year prolapse free rate was 66.7%, since the
      relatively good prognosis was obtained by multiple resections. CONCLUSION: The
      cases that multiple resections with R0 were able to perform for the metastases
      were analyzed. Although cases which become finally to be unresectable exist, it
      is suggested that the relatively good prognosis might be obtained by multiple
      resections for metastases.

PMID- 29362322
TI  - [A Case of Resected Superior Sulcus Tumor with Pathological Complete Response
      after Trimodality Therapy].
AB  - The current case was 73-year-oldwoman. She was referredto our hospital for an
      abnormal shadow of chest X-ray in the upper right lung field. Chest CT showed 3.5
      cm of tumor located at the apex of right lobe with invasion of the chest wall.
      The tumor was diagnosed as squamous cell carcinoma using CT guided needle
      biopsy(superior sulcus tumor, clinical T3N0M0, Stage II B). The neoadjuvant
      therapy, 4 courses of chemotherapy(CBDCA plus PTX)andconcurrent radiotherapy(45
      Gy/25 Fr)was performed. Chest CT revealed that tumor size was decreased to 2.3 cm
      in a diameter, and therapeutic effect was decided as partial response(34%). Upper
      right lobectomy combinedwith the chest wall(1th to 3th ribs)andmed iastinal lymph
      node dissection were performed. The pathological specimens showed no residual
      cancer cells(Ef3, pathological complete response[pCR]). She discharged without
      complications at 10 days after surgery. It is important to collect cases which
      obtainedpCR for development of more effective preoperative therapy.

PMID- 29362323
TI  - [A Case of Retroperitoneal Liposarcoma Resected 6 Times in 24 Years].
AB  - We report a long-surviving case of retroperitoneal liposarcoma requiring 6
      operations in 24 years. A 56-year-old female was diagnosed with liposarcoma and
      it was resected for the first time in 1991. The pathological diagnosis was well
      differentiated liposarcoma. Thereafter, we resected recurrences in the
      retroperitoneum in July 2008, with the left half of the colon in June 2011. Then,
      we resected the pancreatic tails, spleen, accessory spleen, left adrenal gland,
      left kidney, and part of the diaphragm in October 2012, and part of the
      diaphragm, descending colon, and jejunum in October 2014. At this time, there
      were growing recurrences removed from the pancreatic tails. There is no evidence
      of recurrence after 24 years after the first resection. In this case, it was
      thought that the factor correlated with long survival was actively resecting
      recurrences and recognizing high-grade dedifferentiated type liposarcoma at an
      early stage.

PMID- 29362324
TI  - [Three Cases of Obstructive Left-Sided Colon Cancer Resected by Laparoscopic
      Surgery].
AB  - We report 3 cases of obstructive left-sided colon cancer that could be treated
      with laparoscopic resection.Case 1: A 25- year-old man was given a diagnosis of
      colonic obstruction due to transverse colon cancer.Twenty -four days after
      decompression by a nasointestinal tube, we performed a laparoscopic partial
      colectomy.Case 2: A 75-year-old woman was given a diagnosis of colonic
      obstruction due to sigmoid colon.Forty -nine days after decompression by a
      laparoscopic transverse colostomy, we performed a laparoscopic sigmoidectomy.Case
      3: A 48-year-old man was given a diagnosis of colonic obstruction due to sigmoid
      colon cancer.Twenty -two days after decompression by colonic stent, we performed
      a laparoscopic sigmoidectomy.In these 3 cases, decompression was sufficient when
      resecting the primary lesions, and the operations could be completed
      laparoscopically.Elective radical surgery was possible by resolution of oncologic
      emergency state.

PMID- 29362326
TI  - [An Analysis of Perforated Gastric Cancer with Acute Peritonitis in Our
      Hospital].
AB  - Perforated gastric cancer is relatively rare and the incidence is reported about
      1% of all the cases of gastric cancer. We retrospectively analyzed the clinical
      data of the consecutive 12 patients with perforated gastric cancer who underwent
      operation in our hospital between January 2005 and December 2016. There were 5
      men and 7 women, with an average age of 65.8 years old(34-87). Perforated gastric
      cancer occurred in the region U(1 cases), M(6 cases), L(5 cases). There were 11
      cases with distant metastasis. We could successfully diagnosed as perforated
      gastric cancer in 8 cases before emergency operation. Gastrectomy was performed
      in 5 cases. However, the curative resection was performed only 1 case. Prognosis
      of perforated gastric cancer is poor. We considered as an appropriate two-step
      surgical strategy that the first step of surgery is an acute peritonitis
      treatment followed by radical gastrectomy with lymphadenectomy.

PMID- 29362325
TI  - [Early Surgery for Acute Cholecystitis Complicated with Gallbladder Cancer].
AB  - The present study involved 6 patients who had urgent surgery for acute
      cholecystitis(AC)complicated with gallbladder cancer(GBC)in our hospital from
      January 2014 to December 2016. We analyzed the clinical outcome of early surgery
      for AC complicated with GBC. According to Tokyo Guidelines 2013, the AC severity
      was classified as Mild 1 case, Moderate 5 cases. Only one patient was diagnosed
      with GBC before the operation for AC. The others were during or after the
      laparoscopic cholecystectomy. Histopathologically, all patients had Stage II
      disease or greater. Two patients had adjunctive radical operation with the wedge
      resection of the gallbladder bed, lymphadenectomy and bile duct resection, and
      they survived without recurrence for 28 months and 12 months, respectively. Of
      the 3 patients without any additional surgery, 2 patients died in several months
      after the operation. In consideration of the concurrence of GBC, early surgery
      for AC must be decided carefully.

PMID- 29362327
TI  - [Pancreas Bed Recurrence Resection Combined with Celiac and Common Hepatic
      Arterial Resection after Distal Pancreatectomy for Pancreatic Cancer].
AB  - CASE PRESENTATION: A 53-year-old male underwent distal pancreatectomy with
      splenectomy for pancreatic body cancer. An increasing mass in the soft tissue
      around the common hepatic artery was detected 1 year after the primary resection
      and he was referred to our hospital. A low density mass measuring 16mm in length
      was detected around the common hepatic artery by dynamic contrast enhanced
      computed tomography. We diagnosed as pancreatic cancer recurrence in the pancreas
      bed. We performed a recurred mass resection combined with celiac and common
      hepatic artery resection, portal vein resection and reconstruction. Pathological
      examination revealed the cancer recurrence in connective tissue including nerve
      plexus. Adenocarcinoma cells expanded along with the nerve plexus. The tumor
      invaded the adventitia of the common hepatic artery. R0 resection was confirmed
      without exposure of cancer cells to margin. He was discharged on postoperative
      day 12 without any complication. He survived for 6 months after recurrence
      resection without metastasis. CONCLUSION: We experienced a case of local
      recurrence of pancreatic cancer successfully performed R0 resection in
      combination with CHA and CEA resection.

PMID- 29362328
TI  - [Treatment of Regorafenib in Patients with Metastatic or Unresectable
      Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib].
AB  - Imatinibmesylate has dramatically improved the survival with unresectable or
      metastatic GIST, whereas many patients subsequently develop imatinib resistance.
      Followed by sunitinib, regorafenib has been approved since 2013 in Japan. We
      aimed to assess efficacy and safety of regorafenibin GIST patients in clinical
      setting. The study was conducted between August 2013 and April 2016, among 11
      patients with GIST treated by regorafenib. The median treatment duration was 8.4
      months. The median progression-free survival(PFS)was 7.4 months. Nine patients
      experienced at least one Grade 3 or 4 toxicity from regorafenib. The most common
      Grade 3 toxicity was hand-and-foot skin reactions(4 of 11; 36.4%), followed by
      hypertension(3 of 11; 27.3%). Dose reduction was required in 8 patients. Although
      dose modifications due to toxicities were very common, some patients achieved
      long PFS with regorafenibtreatment.

PMID- 29362329
TI  - [A Case of Sigmoid Colon Cancer It Was Found from Penetration of Sigmoid
      Diverticulum].
AB  - A 52-year-old woman presented with sudden left lower abdominal pain, fever, and
      vomiting. As the symptom got improved immediately she went home then. She
      consulted our hospital with chief complaint of the left lower abdominal mass.
      Abdominal computed tomography revealed sigmoid colon cancer with abscess. She was
      diagnosed with sigmoid colon cancer via colonoscopy. Sigmoidectomy including
      partial resection of the abdominal wall was performed(D3 lymphadenectomy).
      Surgical specimen showed penetration of diverticulum on mucous membrane of the
      lesion which had been thought of a abdominal wall permeation and a tumor of I sp
      type at anal side. Pathological examination showed diverticulitis with
      penetration and the tumor was tubular adenocarcinoma(tub1, pT1bpN0, pStage I ).
      We had doubted penetration of sigmoid colon cancer most, but the cause of
      penetration turned out to be diverticulitis. We experienced a case in which we
      could performed surgery of sigmoid colon cancer and penetration of diverticulum
      at the same time.

PMID- 29362330
TI  - [Two Cases of Colon Metastasis of Gastric Cancer by Different Metastasis
      Pathway].
AB  - We treated 2 cases ofcolon metastasis ofgastric cancer considered to be caused by
      different pathway. Case 1 was a 55- year-old male with gastric cancer associated
      with metastases for lymph node, gallbladder, and liver. Curative surgical
      treatment of distal gastrectomy, partial hepatectomy, cholecystectomy and lymph
      node dissection was performed. The final find- ing was, L, Less, Type 3,
      pT4b(GB), tub2, pN3a(10/20), sP0, CY0, pH1, pM1, Stage IV , R0. Ten months after,
      ileocecal resection was performed, as a tumor was detected in the cecum. It was a
      submucosal tumor of well to moderately differentiated adenocarcinoma, and
      diagnosed as a metastasis ofgastric cancer. Case 2 was a 59-year-old male who
      received total gastrectomy. The final finding was UE, Less, Type 4, tub2-por2,
      pT4a, pN2(5/19), cM0, sP0, CY0, Stage III B, R1. One year and 10 months later,
      unevenness and redness in the mucosal membrane ofthe transverse colon occurred.
      Signet-ring cells were observed by the endoscopic biopsy, and colon metastasis
      ofstomach cancer was diagnosed. Consequently, transverse colectomy was performed.
      Diffused invasion of cancer cells was observed in all layers of the wall, which
      was considered as metastasis via gastrocolic ligament. Although colon metastasis
      ofstomach cancer is rare, its pathway varies, such as infiltration, direct
      invasion, hematogenous, and lymphogenous. Form oflesion also varies. For
      diagnosis ofcolon lesion occurring during follow-up after gastric cancer, these
      points should be noted.

PMID- 29362331
TI  - [Surgical Case of Ulcerative Colitis Accompanied with Rectal Cancer Combined with
      Transanal Minimally Invasive Surgery].
AB  - A46 -year-old man developed ulcerative colitis at the age of 19 years. Although
      the colitis was medically treated, it relapsed and repeated over time. Periodic
      lower gastrointestinal endoscopy revealed lower rectal cancer, and he was
      referred to our department of surgery. Previous steroid therapy induced diabetes,
      and he was obese, with a height of 170.3 cm, weight of 89.6 kg, and BMI of 30.89
      kg/m2, indicating that laparoscopic dissection near the anus would be difficult
      to perform. Therefore, the patient was scheduled for transanal minimally invasive
      surgery(TAMIS). The surgery involved as much laparoscopic rectal dissection as
      possible in the ventral to dorsal direction, followed by the TAMIS procedure.
      Dissection was started from the dentate line, and, after the closure of the anal
      stump, GelPOINT was placed, and made continuous with the previous dissection
      layer by applying the technique of down-to-up total mesorectal excision(TME)by
      TAMIS. The large intestine was excised through a small abdominal incision to
      create an ileal pouch, hand-sewn anastomosis was performed transanally to create
      a temporary colostomy, and the surgery was completed. Regarding TAMIS-TME several
      problems remain to be solved, including an understanding of its unique anatomy
      and the mastery of single-port surgical techniques. However, the herein reported
      patient with a high BMI had a definite indication for TAMIS-TME.

PMID- 29362332
TI  - [A Case of Multiple Tumor Neurosurgery for Brain Metastasis of Colorectal
      Cancer].
AB  - We report a patient with brain metastasis of rectal cancer who underwent
      metastatic tumor resection 3 times. In March 2012, a 76-years-old man, diagnosed
      with Stage III a rectal cancer, underwent Hartmann's operation. The lung
      metastasis was confirmed in July and November 2013, surgical resection for
      pulmonary metastasis was performed 2 times. In January 2016, he had difficulty of
      speaking, and isolated brain tumor was found. We performed surgical resection of
      brain metastasis in February 2016. In March and July 2016, the gamma knife
      radiosurgery was performed for other brain metastasis. In July 2016, he occurred
      nausea, headache and right identity hemi-blindness. Two new brain tumors were
      revealed. We performed surgical resection again. Three months after second brain
      surgery, he had dysarthria and a solitary brain tumor was confirmed. We performed
      third neurosurgical resection. All tumors of brain were found to be metastasis
      from rectal cancer in histological study. Currently, 16 months have passed since
      the first diagnosis of brain metastasis of this patient, and the quality of life
      was good relatively. The prognosis of the patients with brain metastasis is poor
      generally. However, this case suggested that multiple surgical resection of brain
      metastasis could improve prognosis and quality of life of patients. Accumulation
      of further cases is needed.

PMID- 29362333
TI  - [Chemoradiotherapy with S-1 for Recurrence Cases of Colorectal Cancer].
AB  - INTRODUCTION: Although chemotherapy is the main treatment for recurrent
      colorectal cancer, the utility of radiotherapy as a local treatment has been
      widely reported. We performed chemoradiotherapy with S-1 for cases with
      recurrence after surgery, and the outcomes are reported herein. MATERIALS AND
      METHODS: Chemoradiotherapy with S-1 was performed in 4 cases. S-1 was
      administered for 2 weeks during the irradiation period, and the off period
      provided was 1 week. RESULTS: X-ray irradiation was performed in 2 cases and
      proton beam irradiation in the other 2. The progression free periods of the 2
      cases receiving proton beam irradiation were 31 months and 36 months. In
      contrast, the progression free periods of the 2 cases given X-ray irradiation
      were 24 months and 21 months. DISCUSSION: It is known that S-1 not only achieves
      a high anticancer effect via dihydropyrimidine dehydrogenase(DPD)inhibition,
      which is a major metabolic pathway of 5-FU, but also increases the radiation
      susceptibility of malignancies. S-1 is regarded as an ideal anticancer agent when
      used in combination with radiation therapy. Since the local control achieved in
      our 4 cases was good, chemoradiotherapy with S-1 was considered to be a useful
      treatment.

PMID- 29362334
TI  - [Usefulness of Vacuum-Assisted Biopsy(VAB)at Initial Biopsy].
AB  - In recent years, breast micro-lesions such as ductal carcinoma in situ(DCIS)were
      detected with progress of the image diagnosis. We investigated the usefulness of
      vacuum-assisted biopsy(VAB)for initial biopsy of breast tumors. We analyzed 32
      cases of VAB performed for breast tumors. The pathological diagnosis of the
      biopsy specimens was malignant lesions in 10 cases, border-line lesions in 1 and
      benign lesions in 21 cases. 11 cases underwent surgery and the final
      histopathological diagnosis was the same in 10 of them. One case histopathology
      varied from DCIS to invasive ductal carcinoma(IDC). It was suggested that VAB at
      initial biopsy was a useful biopsy method.

PMID- 29362335
TI  - [A Case Report of Resectable Leiomyosarcoma of the Duodenum Origin Invading to
      the Inferior Vena Cava].
AB  - A 40's woman had a complaint of abdominal and back pain. Enhanced CT visualized a
      large retroperitoneal tumor and huge multiple myomas of the uterus. The tumor was
      10cm in diameter and located in the anterior of the inferior vena cava, and
      progressed from the posterior of the duodenum to the abdominal aortic
      bifurcation. Diffusion-weighted MR image showed the tumor with high signal
      intensity. Upper gastrointestinal endoscopy revealed a type 2 tumor at the anal
      side of the Vater. The patient was performed curativly abdominal total
      hysterectomy and pancreaticoduodenectomy with inferior vena cava resection.
      Immunohistochemical examination showed that the tumor cells were negative for
      CD34 and c-kit, and positive for desmin and a-SMA. The tumor was
      histopathologically diagnosed as leiomyosarcoma originating from the duodenum.

PMID- 29362336
TI  - [A Case Survived Long Period after Repeated Operation against the Small
      Intestinal GIST with Perforation].
AB  - A patient was 60-year-old man. In March 2011, the small bowel tumor with
      perforation was found and the partial resection of small intestine was urgently
      performed. KIT of resected specimen was positive. Then, diagnosis as GIST was
      defined. Oral administration of imatinib was started, but it was finished in 5
      months because of development of the systemic edema. In February 2013, the
      abdominal CT revealed a tumor of 20 cm in size in the pelvis. Upon laparotomy, we
      detected the GIST recurrence generated at the region of small intestine
      anastomosis where manipulated previously, then resected all of tumor and
      partially small intestine. Afterward, we diagnosed as a recurrence of GIST. In
      March 2014, the abdominal CT found 4 cm sized mesenteric tumor and 2 cm sized
      abdominal wall tumor. The laparotomy was performed and we found 5 disseminated
      nodules intraperitoneally. We confirmed that all of these disseminated nodules
      were successfully removed. We defined them as re-recurrence of GIST. Six years
      and 5 months have elapsed since the first operation was performed, but there is
      no sign of three times recurrence.

PMID- 29362337
TI  - [A Case of Metastatic Carcinoma of Anal Fistula].
AB  - A 58-year-old man underwent rectal resection(D2 dissection)for rectal cancer and
      liver/lung metastases in August 2009. Histopathological findings were Ra, type 2,
      70*80mm, tub1>tub2, int, pSI(peritoneum), INF b, ly1, v1, pN1(2/13), pPM0, pDM0,
      M1a(H1, PUL1), fStage IV . The lung metastasis had disappeared on chest CT after
      postoperative chemotherapy and we were able to perform radical resection of the
      liver metastasis by performing hepatectomy twice. In October 2013, anal pain
      appeared and a painful tumor approximately 2 cm in size was found in the 5
      o'clock direction of the anus. Biopsy revealed a well-differentiated tubular
      adenocarcinoma similar to rectal cancer, and it was diagnosed as a fistula
      metastasis of rectal cancer.We performed chemoradiotherapy(S-1 120mg/day plus RT
      60 Gy/30 Fr)as surgery was recommended but refused. As a result, the tumor
      reduced markedly in size. In December 2015, the tumor enlarged in size and the
      patient and family requested surgery. We, therefore, performed abdominoperineal
      resection. Currently, the patient is alive at 18 months after surgery with no
      recurrence.

PMID- 29362338
TI  - [A Resected Case of UR-LA Pancreatic Tail Cancer with Aortic Invasion after
      Chemoradiotherapy].
AB  - A 70-year-old male was referred to our hospital because of weight loss and
      epigastric discomfort. CT showed an irregularshaped, low-density tumor, 12 cm in
      diameter in the tail of the pancreas. This tumor widely invaded to the left
      kidney and to the anterior and left lateral sides of the aorta in spite of no
      involvement of celiac and superior mesenteric arteries. Moreover, it closely
      contacted with the stomach and the spleen. EUS-fine-needle aspiration biopsy of
      the tumor detected adenocarcinoma. Thus, he was diagnosed with UR-LA pancreatic
      cancer with aortic invasion. He received combination chemotherapy(S-1 plus
      gemcitabine[GEM])and 50.4 Gy 3-dimensional conformal radiation therapy, but this
      therapy had no expected effect. We changed the regimen to GEM plus nab-PTX. After
      1 course of changed regimen, the tumor ruptured into the stomach and endoscopic
      debridement of the necrotic tissue was performed. Twenty-six days later, We
      performed distal pancreatectomy with splenectomy, total gastrectomy, left
      nephrectomy, left adrenalectomy, and segmental resection of the colon. The tumor
      was detached from the aorta as much as possible. The final diagnosis was pT3N0M0,
      pStage II A. Fifty-nine days after operation, we restarted GEM plus nab-PTX
      therapy. However, a cerebral infarction suddenly occurred, and we discontinued
      the chemotherapy. Five months after the operation, he died of cancerous
      peritonitis.

PMID- 29362339
TI  - [A Case of Stage IV Metaplastic Breast Cancer in Which Primary Tumor Was Removed
      after Treatment with Anti-HER2 Systemic Therapy].
AB  - The patient was a 58-year-oldpostmenopausal woman. Vacuum assistedbiopsy of the
      left breast tumor revealedinvasive ductal carcinoma. Immunohistochemical
      examination was negative for estrogen receptor(ER), negative for progesterone
      receptor(PgR), andshowedan HER2 score of 3+. FDG-PET/CT revealedmultiple
      metastases to the left supracravicular and axillary lymph nodes and lungs. She
      was diagnosed with HER2-positive T3N3M1, Stage IV breast cancer. A 2-year regimen
      of chemotherapy with trastuzumab andvinorelbine achieveda complete response with
      regardto the metastatic sites; however, the size of the primary tumor increasedd
      espite the chemotherapy, andsurgical resection of the left breast with axillary
      lymph node dissection was performed for local control. Pathological examination
      of the surgical specimen revealed metaplastic carcinoma with sarcoma component
      surrounded by non-invasive ductal carcinoma. No component of invasive ductal
      carcinoma was found. Immunohistochemically, metaplastic carcinoma was negative
      for ER, negative for PgR, andrevealedan HER2 score of 0. There was discordance of
      HER2 status between pre- andpost -chemotherapy. The patient receivedno further
      chemotherapy following surgery andhas been without disease progression for 6
      years. We suggest there is heterogeneity, that is, the metastatic sites andthe
      partial primary tumor were HER2-positive invasive ductal carcinoma and the
      remainder of the primary tumor was triple negative metaplastic carcinoma. As a
      result, the patient was able to discontinue chemotherapy with higher quality of
      life.

PMID- 29362340
TI  - [A Case of Double Lung and Gastric Cancer Involving Para-Aortic Lymph Node
      Metastasis with Difficult Preoperative Diagnosis].
AB  - A man in his 60s was admitted to our hospital with anemia. An endoscopic
      examination revealed advanced gastric cancer. CT revealed peri-gastric and para
      aortic lymphadenopathy, and a nodular shadow(20mm)in the lower lobe of the right
      lung. PET-CT revealed abnormal uptake in the para-aortic lymph node and stomach
      wall and the nodular shadow in the right lung. A bronchoscopy revealed pulmonary
      adenocarcinoma. From the above, he was diagnosed with gastric cancer(cT4a, cN2,
      cM1, cStage IV )and lung cancer(cT2a, cN0, cM0, cStage I B). Because of gastric
      bleeding, we decided to operate on the gastric cancer before the lung cancer.
      First, total gastrectomy, splenectomy, and cholecystectomy were performed and
      then dissection of lymph node No. 16was performed. Histopathological examination
      indicated that lymph node No. 16was common to lung cancer, so the final diagnosis
      was gastric cancer(pT4a, pN0, cM0, fStage II A)and lung cancer(cT2a, cN0, pM1,
      fStage IV ). In this case, lymphadenectomy of No. 16in the first and pathological
      diagnosis during surgery could help us avoid splenectomy and cholecystectomy, and
      could reduce invasion.

PMID- 29362341
TI  - [Usefulness of Laparoscopic Stoma Creation for Unresectable Colorectal Cancer].
AB  - Laparoscopic stoma creation enables good visualization of viscera within the
      abdominal cavity to ensure adequate mobilization of the large intestine.
      Laparoscopic stoma creation/construction was indicated and performed at our
      hospital in 7 patients who were diagnosed with unresectable colorectal cancer
      between July 2015 and May 2017. Duringthe ileostomy procedure, we made a skin
      incision at the stoma site and performed a single-incision(3-port)laparoscopic
      surgery. For the colostomy procedure, we made a small incision at the umbilicus
      and mobilized the large intestine with laparoscopic dissection of any
      interveningadhesions. Operation time ranged between 34 and 127 minutes, and the
      volume of intraoperative blood loss was low in all cases. There were no fatal
      complications related to the operation. Laparoscopic stoma creation can be
      performed safely and may be useful for staging of malignant colorectal tumors and
      reducing the risk of complications.

PMID- 29362342
TI  - [A Case Report of Robotic Assisted Laparoscopic Low Anterior Resection in a
      Patient with Rectal Cancer and Polysplenia Syndrome].
AB  - Polysplenia syndrome is a rare congenital disease characterized by variable
      thoracic and abdominal anomalies. A man in his 70s was diagnosed with rectal
      cancer by close exploration for fecal occult blood. A barium enema revealed a
      type 1 rectal tumor andwith non-rotation of intestine. CT revealed multiple
      abnormalities: a polyspleen, preduodenal portal vein, congenital absence of the
      pancreatic tail, bilateral superior vena cava, andbilateral bilobedlung. Basedon
      these findings, the patient was diagnosedas having rectal cancer with polysplenia
      syndrome andtreatedwith robotic assistedlaparoscopic low anterior resection. At
      operation, the whole colon was located in the left side of the abdominal cavity.
      The whole colon adhered with each other. The ileocecum adheredto the front of the
      aorta andthe right iliac artery. In the pelvis, anatomical abnormality was not
      detectedandrectal mobilization andresection was performedas usual. The patient
      hadno signs of recurrence of the rectal cancer. This is the first case
      presentation of laparoscopic low anterior resection in a patient with rectal
      cancer and polysplenia syndrome.

PMID- 29362343
TI  - [A Patient Underwent Pancreaticoduodenectomy with Reconstruction of Replaced
      Right Hepatic Artery].
AB  - A 78 year-old man was diagnosed as a pancreatic cancer in department of
      gastroenterology in our hospital. Enhanced computed tomography demonstrated an
      aberrant right hepatic artery(ARHA)arising from superior mesenteric artery(SMA).
      We conducted sub-stomach preserving pancreaticoduodenectomy(SSPPD- II A-1). As
      the preoperative diagnosis, right hepatic artery(RHA)was arising from SMA and
      running through the tumor, and we resected the ARHA with the tumor and
      reconstructed RHA to gastroduodenal artery(GDA). Pathological diagnosis was non
      invasive tumor with neither lymph node metastasis nor invasion of the
      vasculature. We report a case of the patient underwent pancreaticoduodenectomy
      with reconstruction of aberrant right hepatic artery.

PMID- 29362344
TI  - [A Case of Rectal Cancer with Multiple Pulmonary and Liver Metastases Could Be
      Resected through Chemotherapy].
AB  - The patient was a 47-year-old man, whose chief complaint was melena. He visited a
      nearby hospital, and further evaluation showed rectal cancer invading the
      prostate, with multiple lung and liver metastases. The clinical diagnosis was
      cT4b(prostate), cN1, cM1b(H2, PUL2), cStage IV . We performed colostomy in the
      transverse colon prior to chemotherapy. He was administered 1 course of mFOLFOX6
      plus bevacizumab and 7 courses of FOLFOXIRI plus bevacizumab. The primary tumor
      showed PR. The liver metastases were localized and shrunken, while the lung
      metastases disappeared. Approximately 6 months after the start of chemotherapy, a
      laparoscopic total pelvic exenteration and ileal conduit were performed following
      the diagnosis of ycT4b(prostate), ycN1, ycM1a(H2), ycStage IV . About 3 months
      later, a partial resection of the left liver lobes(S1 and S5/S8)was performed
      laparoscopically. He has been cancer-free for 8 months.

PMID- 29362345
TI  - [A Case of Ascending Colon Cancer with Lynch Syndrome Who Underwent XELOX
      Adjuvant Chemotherapy].
AB  - Lynch syndrome is an inherited syndrome with the development of the colorectal
      and various other cancers. Lynch syndrome is caused by mutations in the mismatch
      repair genes. A 33 year-old male underwent XELOX adjuvant chemotherapy for
      ascending colon cancer with Lynch syndrome. Although efficacy of 5-FU is not
      demonstrated in Lynch syndrome, MOSAIC trial had suggested a benefit from FOLFOX
      compared with 5-FU in patients who have colorectal cancer with Lynch syndrome.
      Oxaliplatin-based adjuvant chemotherapy can be a therapeutic option for
      colorectal cancer in lynch syndrome patients.

PMID- 29362346
TI  - [A Case of Rectal Cancer with Multiple Endocrine Neoplasia Type 2].
AB  - A 63-year-old man with multiple endocrine neoplasia type 2(MEN2)was admitted to
      the hospital because of positive fecal occult blood tests. Colonoscopy revealed a
      50mm type 2 tumor at the rectum, which was diagnosed as an adenocarcinoma based
      on histology. Since there was no apparent distant metastasis, laparoscopy
      assisted low anterior resection with regional lymph node dissection was
      performed. The final diagnosis was pT3, pN0, pM0, pStage II . Almost all patients
      with MEN2 have RET mutations, and they are resistant to EGFR inhibitors. Those
      who have thyroid cancer with RET mutations are often given a RET kinase
      inhibitor. In this case, if the patient develops recurrent rectal cancer, it
      warrants checking for RET mutations and using a multi-kinase inhibitor.

PMID- 29362347
TI  - [A Case of Endocrine Cell Carcinoma of the Transverse Colon with Very Poor
      Prognosis, Onset with Bowel Obstruction].
AB  - We report a case of endocrine cell carcinoma of the colon with very poor
      prognosis, onset with bowel obstruction and multiple liver metastases. The
      patient was a 77-year-old man who underwent left hemicolectomy after a colon
      stent treatment for bowel obstruction due to cancer of the transverse colon with
      unresectable multiple liver metastases. Chemotherapy was not initiated because of
      his poor health. He died of primary cancer 52 days after the surgery. Endocrine
      cell carcinoma of the large intestine has a poor prognosis due to an early onset
      of liver and lymph node metastases, as well as peritoneal dissemination. A large
      scale clinical study is needed to establish an effective adjuvant chemotherapy.

PMID- 29362348
TI  - [A Case of Study Stable Disease after Hepatic Arterial Infusion Chemotherapy in a
      Patient with Systemic Chemotherapy-Resistant Liver Metastases of Colon Cancer].
AB  - A 62-year-old man was underwent sigmoidectomy for sigmoid colon cancer(T3N1H0P0,
      Stage III a). He received a postoperative systemic chemotherapy with SOX. Five
      months after the operation, multiple liver metastases were detected by CT scan.
      Systemic chemotherapy(bevacizumab and SOX, bevacizumab and FOLFIRI)did not reduce
      the liver metastases. So 4 courses of hepatic arterial infusion(HAI)chemotherapy
      with CDDP 10mg/day and 5-FU 500mg/day for 2weeks were performed without severe
      adverse events. All the liver metastases decreased in size remarkably, and the
      hepatic resection was able to be performed. We think HAI chemotherapy is one of
      the useful options for resistance to systemic chemotherapy for liver metastases
      from colorectal cancer.

PMID- 29362349
TI  - [Brain Metastasis of Triple Negative Breast Cancer after Pathological Complete
      Response to Neoadjuvant Chemotherapy - A Case Report].
AB  - We report the case of a patient with triple negative breast cancer(TNBC)who
      showed isolated brain metastasis relatively soon after pathological complete
      response(pCR)to neoadjuvant chemotherapy. A 45-year-old woman with a diagnosis of
      TNBC(T2N1M0, Stage II B)received neoadjuvant chemotherapy with 5
      FU/epirubicin/cyclophosphamide(FEC), followed by docetaxel. After the neoadjuvant
      chemotherapy, she underwent mastectomy and axillary lymph node dissection.
      Histological examination of the resected specimens revealed pCR. Brain
      metastasis, however, developed 7 months after the resection. She underwent total
      removal of the brain tumor and 50 Gy irradiation to the right frontal lobe.
      Histological examination confirmed a diagnosis of metastasis from TNBC. She is
      doing well with no evidence of disease 81 months after resection of the brain
      metastasis. This case and a review of the literature suggest that the clinician
      should be aware that brain metastasis from breast cancer may develop even after
      achieving pCR to neoadjuvant chemotherapy. Surgical resection followed by
      radiotherapy may provide a survival benefit for selected patients with isolated
      brain metastasis from breast cancer.

PMID- 29362350
TI  - [A Case of Hepatocellular Carcinoma with Right Atrium Tumor Thrombus and Multiple
      Intrahepatic Metastases That Remarkably Responded to Combination Therapy
      Including Surgery].
AB  - The prognosis for hepatocellular carcinoma(HCC)with right atrium tumor
      thrombus(RATT)is dismal and necessary to be treated on as oncologic emergency. We
      report a case of HCC with RATT which was treated with multidisciplinary therapy
      including surgery. After repeated transarterial chemoembolization(TACE)and
      radiofrequency ablation(RFA), a 71-year-old man consulted to our hospital with
      multiple HCC, lung metastasis, and RATT. Left hemihepatectomy, thrombectomy of
      RATT, and 3 months of hepatic arterial infusion chemotherapy(HAIC)was performed,
      and intrahepatic HCCs were controlled. However, during treatment of lung
      metastasis by sorafenib, the patient died of brain metastasis, 3 years after the
      first treatment. Although surgery and HAIC may give a chance of further treatment
      by control of intrahepatic HCCs, stronger regimen for systemic HCC would be
      necessary.

PMID- 29362351
TI  - [A Case of Advanced Breast Cancer with Liver Metastasis Successfully Treated with
      Multi-Disciplinary].
AB  - We report a case of advanced breast cancer with liver metastasis(T2N1M1, Stage IV
      )achieving a significant improvement of QOL by multi-disciplinary therapy. The
      patient was 37-year-old woman who had breast lump and axillary lymph nodes
      swelling with liver metastasis. A core needle biopsy for breast tumor led to a
      diagnosis of an invasive ductal carcinoma, negative for estrogen receptor and
      progesterone receptor, and positive for HER2/neu protein expression. The Ki-67
      positive cell index was 40%. She received 16 courses of DOC plus HER plus
      PER(docetaxel 75mg/m / 2, trastuzumab 6 mg/kg, pertu- zumab 450mg/body, and
      received 4 courses of EC(epirubicin 90mg/m / 2, cyclophosphamide 600 mg/m2). The
      breast lesion and liver metastatic lesion disappeared after chemotherapy. We
      checked up whole body. There was no metastatic lesion. Therefore, we diagnosed a
      clinical complete response. We performed muscle preserving mastectomy and
      axillary lymph nodes dissection. The pathological diagnosis from resected
      specimens were pathological complete response. The surgical margin was negative.
      She was started the endocrine therapy by tamoxifen(20mg/day). Three years after
      surgery, she was well without metastases. Multi-disciplinary therapy can improve
      patient QOL and the clinical outcomes in Stage IV advanced breast cancer.

PMID- 29362352
TI  - Benign Pericardial Schwannoma: Case Report and Summary of Previously Reported
      Cases.
AB  - BACKGROUND Primary pericardial tumors have a prevalence of between 6.7% and 12.8%
      of all tumors arising in the cardiac region. Pericardial schwannoma is a rare
      entity. It arises from the cardiac plexus and vagus nerve innervating the heart.
      Most of the reported cases, have presented with benign behavior, however, in rare
      situations, they can undergo transformation to malignant behavior When comparing
      the prevalence of cardiac tumors to that of pericardial tumors, the latter is
      much lower in occurrence. A review of English literature identified six
      pericardial schwannoma cases. CASE REPORT We present a case of a 30-year-old male
      patient who presented to our center with the chief complaint of six months of
      gradually progressive left chest pain. His past medical history (PMH) was
      positive for panic attacks (for which he was taking beta-blockers), paroxysmal
      tachycardia, sweating, and irritability. A computed tomography chest scan was
      done; a differential diagnosis of paraganglioma was suggested. However,
      histopathological examination confirmed the pericardial mass was a schwannoma.
      The patient was surgically treated by thoracotomy to resect the lesion.
      CONCLUSIONS This case adds to the existing limited literature on pericardial
      schwannoma as the seventh reported case. Neurogenic cardiac tumors; our case
      marks the second case reported to occur in the subcarinal area near the left
      atrium.

PMID- 29362353
TI  - Role of Xeroderma Pigmentosum Group D in Cell Cycle and Apoptosis in Cutaneous
      Squamous Cell Carcinoma A431 Cells.
AB  - BACKGROUND Cutaneous squamous cell carcinoma (cSCC) is the second most widespread
      cancer in humans and its incidence is rising. Novel therapy with better efficacy
      is needed for clinical treatment of cSCC. Many studies have shown the importance
      of DNA repair pathways during the development of cancer. A key nucleotide
      excision repair (NER) protein, xeroderma pigmentosum group D (XPD), is
      responsible for the excision of a large variety of bulky DNA lesions. MATERIAL
      AND METHODS To explore the role of XPD in A431 cells, we overexpressed XPD in
      A431 cells and performed MTT assay, flow cytometry, and Western blot analysis to
      examine cell proliferation, cell apoptosis, and genes expression. RESULTS We
      found that the overexpression of XPD suppressed cell viability, induced cell
      cycle arrest at G1 phase, and promoted cell apoptosis. Additionally, XPD blocked
      the expression of c-myc, cdc25A, and cdk2, and improved the levels of HIPK2 and
      p53. CONCLUSIONS These results provide new evidence to reveal the role of XPD in
      cSCC A431 cells and suggest that XPD may serve as an anti-oncogene during cSCC
      development.

PMID- 29362356
TI  - Suppression of interdiffusion-induced voiding in oxidation of copper nanowires
      with twin-modified surface.
AB  - Cavitation and hollow structures can be introduced in nanomaterials via the
      Kirkendall effect in an alloying or reaction system. By introducing dense
      nanoscale twins into copper nanowires (CuNWs), we change the surface structure
      and prohibit void formation in oxidation of the nanowires. The nanotwinned CuNW
      exhibits faceted surfaces of very few atomic steps as well as a very low vacancy
      generation rate at copper/oxide interfaces. Together they lower the oxidation
      rate and eliminate void formation at the copper/oxide interface. We propose that
      the slow reaction rate together with the highly effective vacancy absorption at
      interfaces leads to a lattice shift in the oxidation reaction. Our findings
      suggest that the nanoscale Kirkendall effect can be manipulated by controlling
      the internal and surface crystal defects of nanomaterials.

PMID- 29362354
TI  - Epsin and Sla2 form assemblies through phospholipid interfaces.
AB  - In clathrin-mediated endocytosis, adapter proteins assemble together with
      clathrin through interactions with specific lipids on the plasma membrane.
      However, the precise mechanism of adapter protein assembly at the cell membrane
      is still unknown. Here, we show that the membrane-proximal domains ENTH of epsin
      and ANTH of Sla2 form complexes through phosphatidylinositol 4,5-bisphosphate
      (PIP2) lipid interfaces. Native mass spectrometry reveals how ENTH and ANTH
      domains form assemblies by sharing PIP2 molecules. Furthermore, crystal
      structures of epsin Ent2 ENTH domain from S. cerevisiae in complex with PIP2 and
      Sla2 ANTH domain from C. thermophilum illustrate how allosteric phospholipid
      binding occurs. A comparison with human ENTH and ANTH domains reveal only the
      human ENTH domain can form a stable hexameric core in presence of PIP2, which
      could explain functional differences between fungal and human epsins. We propose
      a general phospholipid-driven multifaceted assembly mechanism tolerating
      different adapter protein compositions to induce endocytosis.

PMID- 29362357
TI  - Volcanic crystals as time capsules of eruption history.
AB  - Crystals formed prior to a volcanic event can provide evidence of processes
      leading to and timing of eruptions. Clinopyroxene is common in basaltic to
      intermediate volcanoes, however, its ability as a recorder of pre-eruptive
      histories has remained comparatively underexplored. Here we show that novel high
      resolution trace element images of clinopyroxene track eruption triggers and
      timescales at Mount Etna (Sicily, Italy). Chromium (Cr) distribution in
      clinopyroxene from 1974 to 2014 eruptions reveals punctuated episodes of
      intrusion of primitive magma at depth. Magma mixing efficiently triggered
      volcanism (success rate up to 90%), within only 2 weeks of arrival of mafic
      intrusions. Clinopyroxene zonations distinguish between injections of mafic magma
      and regular recharges with more evolved magma, which often fail to tip the system
      to erupt. High Cr zonations can therefore be used to reconstruct past eruptions
      and inform responses to geophysical signals of volcano unrest, potentially
      offering an additional approach to volcano hazard monitoring.

PMID- 29362355
TI  - Hypoxia and hypoxia inducible factor-1alpha are required for normal endometrial
      repair during menstruation.
AB  - Heavy menstrual bleeding (HMB) is common and debilitating, and often requires
      surgery due to hormonal side effects from medical therapies. Here we show that
      transient, physiological hypoxia occurs in the menstrual endometrium to stabilise
      hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We
      report that women with HMB have decreased endometrial HIF-1alpha during
      menstruation and prolonged menstrual bleeding. In a mouse model of simulated
      menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of
      mice under hyperoxia during menses decreases HIF-1alpha induction and delays
      endometrial repair. The same effects are observed upon genetic or pharmacological
      reduction of endometrial HIF-1alpha. Conversely, artificial induction of hypoxia
      by pharmacological stabilisation of HIF-1alpha rescues the delayed endometrial
      repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the
      endometrium and suggest its pharmacological stabilisation during menses offers an
      effective, non-hormonal treatment for women with HMB.

PMID- 29362358
TI  - Therapeutic potential of targeting S100A11 in malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive tumor with an unfavorable
      prognosis. The standard therapeutic approaches are limited to surgery,
      chemotherapy, and radiotherapy. Because the consequent clinical outcome is often
      unsatisfactory, a different approach in MPM treatment is required. S100A11, a
      Ca2+-binding small protein with two EF-hands, is frequently upregulated in
      various human cancers. Interestingly, it has been found that intracellular and
      extracellular S100A11 have different functions in cell viability. In this study,
      we focused on the impact of extracellular S100A11 in MPM and explored the
      therapeutic potential of an S100A11-targeting strategy. We examined the secretion
      level of S100A11 in various kinds of cell lines by enzyme-linked immunosorbent
      assay. Among them, six out of seven MPM cell lines actively secreted S100A11,
      whereas normal mesothelial cell lines did not secrete it. To investigate the role
      of secreted S100A11 in MPM, we inhibited its function by neutralizing S100A11
      with an anti-S100A11 antibody. Interestingly, the antibody significantly
      inhibited the proliferation of S100A11-secreting MPM cells in vitro and in vivo.
      Microarray analysis revealed that several pathways including genes involved in
      cell proliferation were negatively enriched in the antibody-treated cell lines.
      In addition, we examined the secretion level of S100A11 in various types of
      pleural effusions. We found that the secretion of S100A11 was significantly
      higher in MPM pleural effusions, compared to others, suggesting the possibility
      for the use of S100A11 as a biomarker. In conclusion, our results indicate that
      extracellular S100A11 plays important roles in MPM and may be a therapeutic
      target in S100A11-secreting MPM.

PMID- 29362360
TI  - Sensitisation to mitoxantrone-induced apoptosis by the oncolytic adenovirus Ad??
      through Bcl-2-dependent attenuation of autophagy.
AB  - Anti-apoptotic Bcl-2 is frequently activated in human malignant cells to promote
      cell survival and inhibit cell death. Replication-selective oncolytic
      adenoviruses deleted in the functional Bcl-2 homologue E1B19K potently synergise
      with apoptosis-inducing chemotherapeutic drugs, including mitoxantrone for
      prostate cancer. Here, we demonstrate that our previously generated oncolytic
      mutant Ad?? (E1B19K- and E1ACR2-deleted) caused potent synergistic apoptotic cell
      death in both drug-sensitive 22Rv1, and drug-insensitive PC3 and PC3M prostate
      cancer cells. The synergistic cell killing was dependent on Bcl-2 expression and
      was prevented by Bcl-2 knockdown, which led to activation of the autophagy
      pathway. Mitoxantrone-induced autophagy, which was decreased in combination with
      Ad??-infection resulting in increased apoptosis. Expression of the viral E1A12S
      protein alone mimicked the synergistic effects with Ad?? in combination with
      mitoxantrone while intact wild-type virus (Ad5) had no effect. Early and late
      stage inhibition of autophagy by Atg7 knockdown and chloroquine respectively,
      promoted apoptotic cell killing with mitoxantrone similar to Ad??. These findings
      revealed currently unexplored actions of E1B19K-deleted oncolytic adenoviruses
      and the central role of Bcl-2 in the synergistic cell killing. This study
      suggests that cancers with functional Bcl-2 expression may be selectively re
      sensitised to drugs by Ad??.

PMID- 29362359
TI  - Impaired DNA damage response signaling by FUS-NLS mutations leads to
      neurodegeneration and FUS aggregate formation.
AB  - Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease.
      Cytoplasmic fused in sarcoma (FUS) aggregates are pathological hallmarks of FUS
      ALS. Proper shuttling between the nucleus and cytoplasm is essential for
      physiological cell function. However, the initial event in the pathophysiology of
      FUS-ALS remains enigmatic. Using human induced pluripotent stem cell (hiPSCs)
      derived motor neurons (MNs), we show that impairment of poly(ADP-ribose)
      polymerase (PARP)-dependent DNA damage response (DDR) signaling due to mutations
      in the FUS nuclear localization sequence (NLS) induces additional cytoplasmic FUS
      mislocalization which in turn results in neurodegeneration and FUS aggregate
      formation. Our work suggests that a key pathophysiologic event in ALS is upstream
      of aggregate formation. Targeting DDR signaling could lead to novel therapeutic
      routes for ameliorating ALS.

PMID- 29362362
TI  - Ag-migration effects on the metastable phase in CaCu3Ti4O12 capacitors.
AB  - The silver migration effect into the metastable phase forms a micro-electric
      path, to enhance the relative dielectric permittivity of CaCu3Ti4O12 ceramics for
      electronic devices. Controlling the sintering time uniquely develops the
      metastable phase of as-sintered CaCu3Ti4O12 ceramics. A post-heating process that
      applies the migration of silver into the metastable phase increases the relative
      dielectric permittivity. At 1 kHz frequency, the relative dielectric permittivity
      at room temperature of the silver-migrated CaCu3Ti4O12 ceramics sintered for 2 h
      is 565.9 * 103, almost 52 times higher than that of the as-sintered CaCu3Ti4O12
      ceramics. The selected area electron diffraction (SAED) patterns of the large and
      small grains were similar, but differed from those of the metastable region,
      including the grain boundary of the as-sintered CaCu3Ti4O12 ceramics sintered for
      2 h by TEM technique. This phenomenon suggests that enabling Ag-migration into
      the metastable phase develops a micro-electric path that improves the relative
      dielectric permittivity of CaCu3Ti4O12 ceramics.

PMID- 29362361
TI  - Whole-exome sequencing identifies common and rare variant metabolic QTLs in a
      Middle Eastern population.
AB  - Metabolomics-genome-wide association studies (mGWAS) have uncovered many
      metabolic quantitative trait loci (mQTLs) influencing human metabolic
      individuality, though predominantly in European cohorts. By combining whole-exome
      sequencing with a high-resolution metabolomics profiling for a highly
      consanguineous Middle Eastern population, we discover 21 common variant and 12
      functional rare variant mQTLs, of which 45% are novel altogether. We fine-map 10
      common variant mQTLs to new metabolite ratio associations, and 11 common variant
      mQTLs to putative protein-altering variants. This is the first work to report
      common and rare variant mQTLs linked to diseases and/or pharmacological targets
      in a consanguineous Arab cohort, with wide implications for precision medicine in
      the Middle East.

PMID- 29362363
TI  - HNRNPH1 is required for rhabdomyosarcoma cell growth and survival.
AB  - Rhabdomyosarcoma (RMS) is an aggressive and difficult to treat cancer
      characterized by a muscle-like phenotype. Although the average 5-y survival rate
      is 65% for newly diagnosed RMS, the treatment options for metastatic disease are
      limited in efficacy, with the 5-y survival rate plummeting to 30%. Heterogenous
      nuclear ribonucleoprotein H1 (HNRNPH1) is an RNA-binding protein that is highly
      expressed in many cancers, including RMS. To determine the role HNRNPH1 plays in
      RMS tumorigenesis, we investigated its expression and effect on growth in three
      cellular models of RMS: RD, RH30, and RH41 cells. Upon knockdown of HNRNPH1,
      growth of all cell lines was reduced, most likely through a combination of
      apoptosis and cell cycle arrest. We then recapitulated this finding by performing
      in vivo xenograft studies, in which knockdown of HNRNPH1 resulted in a reduction
      of tumor formation and growth. We used RNA sequencing to identify changes in gene
      expression after HNRNPH1 knockdown and found altered splicing of some oncogenes.
      Our data contribute to understanding the role of HNRNPH1 in RMS development.

PMID- 29362364
TI  - A Discontinuous Galerkin Model for Fluorescence Loss in Photobleaching.
AB  - Fluorescence loss in photobleaching (FLIP) is a modern microscopy method for
      visualization of transport processes in living cells. This paper presents the
      simulation of FLIP sequences based on a calibrated reaction-diffusion system
      defined on segmented cell images. By the use of a discontinuous Galerkin method,
      the computational complexity is drastically reduced compared to continuous
      Galerkin methods. Using this approach on green fluorescent protein (GFP), we can
      determine its intracellular diffusion constant, the strength of localized
      hindrance to diffusion as well as the permeability of the nuclear membrane for
      GFP passage, directly from the FLIP image series. Thus, we present for the first
      time, to our knowledge, a quantitative computational FLIP method for inferring
      several molecular transport parameters in parallel from FLIP image data acquired
      at commercial microscope systems.

PMID- 29362365
TI  - Fungal networks shape dynamics of bacterial dispersal and community assembly in
      cheese rind microbiomes.
AB  - Most studies of bacterial motility have examined small-scale (micrometer
      centimeter) cell dispersal in monocultures. However, bacteria live in
      multispecies communities, where interactions with other microbes may inhibit or
      facilitate dispersal. Here, we demonstrate that motile bacteria in cheese rind
      microbiomes use physical networks created by filamentous fungi for dispersal, and
      that these interactions can shape microbial community structure. Serratia
      proteamaculans and other motile cheese rind bacteria disperse on fungal networks
      by swimming in the liquid layers formed on fungal hyphae. RNA-sequencing,
      transposon mutagenesis, and comparative genomics identify potential genetic
      mechanisms, including flagella-mediated motility, that control bacterial
      dispersal on hyphae. By manipulating fungal networks in experimental communities,
      we demonstrate that fungal-mediated bacterial dispersal can shift cheese rind
      microbiome composition by promoting the growth of motile over non-motile
      community members. Our single-cell to whole-community systems approach highlights
      the interactive dynamics of bacterial motility in multispecies microbiomes.

PMID- 29362366
TI  - Platelet subpopulations remain despite strong dual agonist stimulation and can be
      characterised using a novel six-colour flow cytometry protocol.
AB  - It is recognised that platelets respond differently to activation, where a
      subpopulation of platelets adopt a procoagulant phenotype while others are
      aggregatory. However, it has not been thoroughly tested whether these
      subpopulations will remain in maximally activated samples, or if they are merely
      a result of different platelet sensitivities to agonist activation. Here
      platelets were activated with gradually increasing concentrations of thrombin
      and/or the GPVI agonist cross-linked collagen-related peptide (CRP-XL). Platelet
      activation was investigated using a novel six-colour flow cytometry protocol
      evaluating exposure of phosphatidylserine, active conformation of the fibrinogen
      receptor alphaIIbbeta3, alpha-granule and lysosomal release (P-selectin and LAMP
      1 exposure), mitochondrial membrane integrity and platelet fragmentation. Upon
      activation by CRP-XL or thrombin+CRP-XL, platelets formed three differently sized
      subpopulations. Normal-sized platelets showed high exposure of aggregatory active
      alphaIIbbeta3 and intact mitochondria, while the smaller platelets and platelet
      fragments showed high exposure of procoagulant phosphatidylserine. The
      distribution of platelets between the differently sized subpopulations remained
      stable despite high agonist concentrations. All three were still present after 30
      and 60 min of activation, showing that all platelets will not have the same
      characteristics even after maximal stimulation. This suggests that platelet
      subpopulations with distinct activation patterns exist within the total platelet
      population.

PMID- 29362368
TI  - Physiological status of plant tissue affects the frequency and types of mutations
      induced by carbon-ion irradiation in Arabidopsis.
AB  - Ionizing radiation including heavy-ion beams has been widely used in mutation
      breeding. Dry seeds, seedlings, and cultured tissues are often used for
      mutagenesis; however, little is known about the differences in induced mutations
      among them. Here, we examined the characteristics of mutations using randomly
      chosen Arabidopsis M2 plants derived from dry seeds and seedlings irradiated with
      carbon ions. The mutation frequency was 1.4-1.9 times higher in dry-seed
      irradiation than in seedling irradiation. This difference was mainly due to the
      three-times higher frequency of insertions and deletions (InDels) in dry-seed
      irradiation than in seedling irradiation. This difference increased the
      proportion of mutations predicted to affect gene function among all mutations
      identified by whole genome re-sequencing. Our results demonstrate that the
      physiological status of plant tissue greatly affects the characteristics of
      mutations induced by ionizing radiation, and that dry seeds are more suitable
      materials than seedlings for inducing loss-of-function mutations. The results
      also showed that single base deletions often occurred in homopolymeric sequences,
      while InDels larger than 2-3 bp often occurred in or near polynucleotide-repeat
      or microhomologous sequences. Interestingly, microhomology was less commonly
      found around large deletions (>=50 bp), suggesting that the rejoining process
      differs depending on the deletion size.

PMID- 29362367
TI  - A hypoxia- and telomerase-responsive oncolytic adenovirus expressing secretable
      trimeric TRAIL triggers tumour-specific apoptosis and promotes viral dispersion
      in TRAIL-resistant glioblastoma.
AB  - Glioblastoma is a highly aggressive and malignant type of cancer that is
      apoptosis resistant and difficult to cure by conventional cancer therapies. In
      this regard, an oncolytic adenovirus that selectively targets the tumour tissue
      and induces tumour cell lysis is a promising treatment option. We designed and
      constructed a hypoxia-responsive and cancer-specific modified human telomerase
      reverse transcriptase (H5CmTERT) promoter to drive replication of an oncolytic
      adenovirus (H5CmTERT-Ad). To enhance the anti-tumour efficacy of H5CmTERT-Ad
      against malignant glioblastoma, we also generated an H5CmTERT-Ad expressing
      secretable trimeric tumour necrosis factor-related apoptosis-inducing ligand
      (H5CmTERT-Ad/TRAIL). H5CmTERT promoter-regulated oncolytic adenoviruses showed
      cancer-specific and superior cell-killing effect in contrast to a cognate control
      oncolytic adenovirus replicating under the control of the endogenous adenovirus
      promoter. The cancer cell-killing effects of H5CmTERT-Ad and H5CmTERT-Ad/TRAIL
      were markedly higher during hypoxia than normoxia owing to hypoxia responsiveness
      of the promoter. H5CmTERT-Ad/TRAIL showed more potent anti-tumour efficacy than
      H5CmTERT-Ad did in a xenograft model of TRAIL-resistant subcutaneous and
      orthotopic glioblastoma through superior induction of apoptosis and more
      extensive virus distribution in the tumour tissue. Altogether, our findings show
      that H5CmTERT-Ad/TRAIL can promote dispersion of an oncolytic adenovirus through
      robust induction of apoptosis in a highly TRAIL-resistant glioblastoma.

PMID- 29362369
TI  - High-temperature operation of electrical injection type-II
      (GaIn)As/Ga(AsSb)/(GaIn)As "W"-quantum well lasers emitting at 1.3 um.
AB  - Electrical injection lasers emitting in the 1.3 MUm wavelength regime based on
      (GaIn)As/Ga(AsSb)/(GaIn)As type-II double "W"-quantum well heterostructures grown
      on GaAs substrate are demonstrated. The structure is designed by applying a fully
      microscopic theory and fabricated using metal organic vapor phase epitaxy.
      Temperature-dependent electroluminescence measurements as well as broad-area edge
      emitting laser studies are carried out in order to characterize the resulting
      devices. Laser emission based on the fundamental type-II transition is
      demonstrated for a 975 MUm long laser bar in the temperature range between 10 
      degrees C and 100  degrees C. The device exhibits a differential efficiency of 41
      % and a threshold current density of 1.0 kA/cm2 at room temperature. Temperature
      dependent laser studies reveal characteristic temperatures of T0 = (132 +/- 3) K
      over the whole temperature range and T1 = (159 +/- 13) K between 10  degrees C
      and 70  degrees C and T1 = (40 +/- 1) K between 80  degrees C and 100  degrees C.

PMID- 29362370
TI  - Active and dynamic mitochondrial S-depalmitoylation revealed by targeted
      fluorescent probes.
AB  - The reversible modification of cysteine residues by thioester formation with
      palmitate (S-palmitoylation) is an abundant lipid post-translational modification
      (PTM) in mammalian systems. S-palmitoylation has been observed on mitochondrial
      proteins, providing an intriguing potential connection between metabolic lipids
      and mitochondrial regulation. However, it is unknown whether and/or how
      mitochondrial S-palmitoylation is regulated. Here we report the development of
      mitoDPPs, targeted fluorescent probes that measure the activity levels of
      "erasers" of S-palmitoylation, acyl-protein thioesterases (APTs), within
      mitochondria of live cells. Using mitoDPPs, we discover active S-depalmitoylation
      in mitochondria, in part mediated by APT1, an S-depalmitoylase previously thought
      to reside in the cytosol and on the Golgi apparatus. We also find that
      perturbation of long-chain acyl-CoA cytoplasm and mitochondrial regulatory
      proteins, respectively, results in selective responses from cytosolic and
      mitochondrial S-depalmitoylases. Altogether, this work reveals that mitochondrial
      S-palmitoylation is actively regulated by "eraser" enzymes that respond to
      alterations in mitochondrial lipid homeostasis.

PMID- 29362372
TI  - High-fidelity entanglement swapping and generation of three-qubit GHZ state using
      asynchronous telecom photon pair sources.
AB  - We experimentally demonstrate a high-fidelity entanglement swapping and a
      generation of the Greenberger-Horne-Zeilinger (GHZ) state using polarization
      entangled photon pairs at telecommunication wavelength produced by spontaneous
      parametric down conversion with continuous-wave pump light. While spatially
      separated sources asynchronously emit photon pairs, the time-resolved photon
      detection guarantees the temporal indistinguishability of photons without active
      timing synchronizations of pump lasers and/or adjustment of optical paths. In the
      experiment, photons are sufficiently narrowed by fiber-based Bragg gratings with
      the central wavelengths of 1541 nm & 1580 nm, and detected by superconducting
      nanowire single-photon detectors with low timing jitters. The observed fidelities
      of the final states for entanglement swapping and the generated three-qubit state
      were 0.84 +/- 0.04 and 0.70 +/- 0.05, respectively.

PMID- 29362371
TI  - KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal
      cancer.
AB  - There are limited data on circulating, cell-free, tumour (ct)DNA analysis in
      locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to
      investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC
      patients who were treated with CAPOX followed by chemoradiotherapy, surgery and
      adjuvant CAPOX +/- cetuximab in a randomised phase II trial. KRAS mutation in
      G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with
      tumours that were mutant and wild-type for these hotspot mutations, respectively,
      according to standard PCR-based analyses on tissue. The detection rate in the
      ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA
      analysis revealed KRAS mutations that were not previously found in tissue. Twenty
      two of these (84.6%) were detected following repeat tissue testing by ddPCR.
      Overall, the ctDNA detection rate in the KRAS mutant population was 66%.
      Detection of KRAS mutation in ctDNA failed to predict prognosis or refine patient
      selection for cetuximab. While this study confirms the feasibility of ctDNA
      analysis in LARC and the high sensitivity of ddPCR, larger series are needed to
      better address the role of ctDNA as a prognostic or predictive tool in this
      setting.

PMID- 29362373
TI  - Streamlined sensory motor communication through cortical reciprocal connectivity
      in a visually guided eye movement task.
AB  - Cortical computation is distributed across multiple areas of the cortex by
      networks of reciprocal connectivity. However, how such connectivity contributes
      to the communication between the connected areas is not clear. In this study, we
      examine the communication between sensory and motor cortices. We develop an eye
      movement task in mice and combine it with optogenetic suppression and two-photon
      calcium imaging techniques. We identify a small region in the secondary motor
      cortex (MOs) that controls eye movements and reciprocally connects with a
      rostrolateral part of the higher visual areas (VRL/A/AL). These two regions
      encode both motor signals and visual information; however, the information flow
      between the regions depends on the direction of the connectivity: motor
      information is conveyed preferentially from the MOs to the VRL/A/AL, and sensory
      information is transferred primarily in the opposite direction. We propose that
      reciprocal connectivity streamlines information flow, enhancing the computational
      capacity of a distributed network.

PMID- 29362374
TI  - Repeated photon and C-ion irradiations in vivo have different impact on
      alteration of tumor characteristics.
AB  - Precise characterization of tumor recurrence and regrowth after radiotherapy are
      important for prognostic understanding of the therapeutic effect. Here, we
      established a novel in vivo mouse model for evaluating the characteristics of
      regrown tumor after repeated photon and carbon ion (C-ion) irradiations. The
      results showed that tumor growth rate, lung metastasis, shortening of the
      survival of the tumor-bearing mice, and tumor microvessel formation were promoted
      2- to 3-fold, and expression of angiogenic and metastatic genes increased 1.5- to
      15-fold in regrown tumors after repeated photon irradiations, whereas repeated C
      ion irradiations did not alter these characteristics. Interestingly, both
      repeated photon and C-ion irradiations did not generate radioresistance, which is
      generally acquired for in vitro treatment. Our results demonstrated that the
      repetition of photon, and not C-ion, irradiations in vivo alter the
      characteristics of the regrown tumor, making it more aggressive without
      acquisition of radioresistance.

PMID- 29362375
TI  - Antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid in
      liver and brain of rats treated by D-galactose.
AB  - Accumulating evidence has suggested that oxidative stress and apoptosis are
      involved in the ageing process. D-galactose (gal) has been reported to cause
      symptoms of ageing in rats, accompanied by liver and brain injuries. Our study
      aimed to investigate the potential antioxidative, anti-inflammatory and anti
      apoptotic effects of ellagic acid and to explore how these effects act on rats in
      a D-gal-induced ageing model. Ageing was induced by subcutaneous injection of D
      gal (100 mg/kg/d for 8 weeks). Ellagic acid was simultaneously administered to
      the D-gal-induced ageing rats once daily by intragastric gavage. Finally, the
      mental condition, body weight, organ index, levels of inflammatory cytokines,
      antioxidative enzymes, and liver function, as well as the expression of pro- and
      anti-apoptotic proteins, were monitored. Our results showed that ellagic acid
      could improve the mental condition, body weight, organ index and significantly
      decrease the levels of inflammatory cytokines, normalize the activities of
      antioxidative enzymes, and modulate the expression of apoptotic protein in ageing
      rats. In conclusion, the results of this study illustrate that ellagic acid was
      suitable for the treatment of some ageing-associated problems, such as oxidative
      stress, and had beneficial effects for age-associated diseases.

PMID- 29362377
TI  - Annual shifts of flow regime alteration: new insights from the Chaishitan
      Reservoir in China.
AB  - Reservoir regulation is variable for flow regime alterations and mainly depends
      on operational objectives and hydro-meteorological conditions. In this study, the
      flow regime metrics (i.e., magnitude, variability and frequency, duration, timing
      and rate of change) are adopted to describe variations in both long-term inflow
      and outflow series of the Chaishitan Reservoir in China. Deviations between the
      inflow and outflow metrics are calculated to assess the flow regime alterations
      at annual scale. Further, dimensions of both time and flow regimes are reduced by
      multivariate statistical analysis, and the regulation patterns and their annual
      shifts are identified. Results show that: four regulation patterns are identified
      from 2004 to 2015. The regulation is gradually enhanced over time with typical
      features of different hydrological years. In dry years, the pattern is slightly
      regulated flow regimes with slightly discharging stored water and flattening
      outflow, moderate stability and intermittency. In normal years, the pattern is
      slightly regulated flow regimes with extremely increasing flow magnitude in the
      pre-nonflood season, high stability and slight intermittency. In wet years, the
      pattern is moderately regulated flow regimes with moderately decreasing flow
      magnitude in the flood season but extremely increasing flow magnitude in the
      nonflood season, slight stability and high intermittency.

PMID- 29362376
TI  - A mouse model of autism implicates endosome pH in the regulation of presynaptic
      calcium entry.
AB  - Psychoactive compounds such as chloroquine and amphetamine act by dissipating the
      pH gradient across intracellular membranes, but the physiological mechanisms that
      normally regulate organelle pH remain poorly understood. Interestingly, recent
      human genetic studies have implicated the endosomal Na+/H+ exchanger NHE9 in both
      autism spectrum disorders (ASD) and attention deficit hyperactivity disorder
      (ADHD). Plasma membrane NHEs regulate cytosolic pH, but the role of intracellular
      isoforms has remained unclear. We now find that inactivation of NHE9 in mice
      reproduces behavioral features of ASD including impaired social interaction,
      repetitive behaviors, and altered sensory processing. Physiological
      characterization reveals hyperacidic endosomes, a cell-autonomous defect in
      glutamate receptor expression and impaired neurotransmitter release due to a
      defect in presynaptic Ca2+ entry. Acute inhibition of synaptic vesicle
      acidification rescues release but without affecting the primary defect due to
      loss of NHE9.

PMID- 29362378
TI  - Comparing different technologies for active TB case-finding among the homeless: a
      transmission-dynamic modelling study.
AB  - Homeless persons have elevated risk of tuberculosis (TB) and are under-served by
      conventional health services. Approaches to active case-finding (ACF) and
      treatment tailored to their needs are required. A transmission-dynamic model was
      developed to assess the effectiveness and efficiency of screening with mobile
      Chest X-ray, GeneXpert, or both. Effectiveness of ACF depends upon the prevalence
      of infection in the population (which determines screening 'yield'), patient
      willingness to wait for GeneXpert results, and treatment adherence. ACF is
      efficient when TB prevalence exceeds 78/100,000 and 46% of drug sensitive TB
      cases and 33% of multi-drug resistant TB cases complete treatment. This threshold
      increases to 92/100,000 if additional post-ACF enhanced case management (ECM)
      increases treatment completion to 85%. Generally, the most efficient option is
      one-step screening of all patients with GeneXpert, but if too many patients (>27%
      without ECM, >19% with ECM) are unwilling to wait the 90 minutes required then
      two-step screening using chest X-ray (which is rapid) followed by GeneXpert for
      confirmation of TB is the most efficient option. Targeted ACF and support
      services benefit health through early successful treatment and averting TB
      transmission and disease. The optimal strategy is setting-specific, requiring
      careful consideration of patients' needs regarding testing and treatment.

PMID- 29362379
TI  - New rapid one-step PCR diagnostic assay for Plasmodium falciparum infective
      mosquitoes.
AB  - An essential component of malaria vector control programmes is the detection of
      Plasmodium falciparum within its mosquito vectors, particularly in the salivary
      glands where the infective sporozoites reside. Several protocols have been
      developed for this purpose; however they require dissection of mosquito specimens
      prior to analysis. Here, a novel one-step RT-qPCR TaqMan diagnostic assay was
      developed for mosquitoes with infective Plasmodium falciparum sporozoites in the
      salivary glands. It is based on detection of the sporozoite-specific Pfslarp and
      Pfplp1 gene transcripts. These transcripts were chosen based on bioinformatics
      analysis, and experimentally verified to be overexpressed in the salivary gland
      sporozoite stage of the parasite compared to other mosquito parasite stages. The
      proof of principle and the performance of the assay were demonstrated using
      RNAlater preserved mosquito samples. Tests of analytical sensitivity showed the
      novel TaqMan assay to be 100% accurate, although its performance in the field
      needs to be further demonstrated. This method has no requirement for dissection
      and post-PCR processing and thus is simple and rapid to perform in individual
      mosquitoes or mosquito pools. It can be used in single or multiplex formats also
      targeting additional markers expressed in different tissues, such as
      detoxification enzymes associated with insecticide resistance.

PMID- 29362380
TI  - Clinical Evaluation of the Immunochromatographic System Using Silver
      Amplification for the Rapid Detection of Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae infection is conventionally diagnosed using serum antibody
      testing, microbial culture, and genetic testing. Recently, immunochromatography
      based rapid mycoplasma antigen test kits have been developed and commercialised
      for rapid diagnosis of M. pneumoniae infection. However, as these kits do not
      provide sufficient sensitivity and specificity, a rapid test kit with improved
      accuracy is desired. The present prospective study evaluated a rapid M.
      pneumoniae diagnostic system utilizing a newly developed silver amplification
      immunochromatography (SAI) system. We performed dilution sensitivity test and the
      prospective clinical study evaluating the SAI system. The subjects of the
      clinical study included both children and adults. All patients suspected to have
      mycoplasma pneumonia (169 patients) were sequentially enrolled. Twelve patients
      did not agree to participate and 157 patients were enrolled in the study. The
      results demonstrate excellent performance of this system with 90.4% sensitivity
      and 100.0% specificity compared with real-time polymerase chain reaction. When
      compared with loop-mediated isothermal amplification (LAMP) methods, the results
      also demonstrate a high performance of this system with 93.0% sensitivity and
      100.0% specificity. The SAI system uses a dedicated device for automatic analysis
      and reading, making it highly objective, and requires less human power,
      supporting its usefulness in clinical settings.

PMID- 29362381
TI  - Gene expression of human endometrial L-selectin ligand in relation to the phases
      of the natural menstrual cycle.
AB  - This study investigates peptide components of L-selectin ligand (LSL) and their
      gene expressions in human endometrium during the natural menstrual cycle. We
      recruited 41 endometrial samples from reproductive-aged women with leiomyoma and
      undergoing hysterectomy and 11 endometrial samples from menopausal women as
      controls. Immunohistochemistry revealed strong MECA-79 expression from the early
      through the mid-secretory phase and low expression in menopausal endometrium.
      Five peptide components of LSL were detected in reproductive and menopausal
      endometrium by one-step quantitative RT-PCR: podocalyxin, endomucin, nepmucin,
      GlyCAM-1, and CD34. Endomucin differed significantly between the proliferative
      and early-secretory phases. CHST2 and CHST4 genes (which are involved in the
      generation of LSL epitopes) were expressed without significant differences among
      phases. The gene expression of progesterone receptor decreased from the
      proliferative to the late-secretory phase, and the difference was significant.
      However, estrogen receptor alpha expression showed stability among phases. The
      significant expression of endomucin between the proliferative and early-secretory
      phases might play a vital role in endometrial receptivity. Further studies are
      needed to investigate the factors that regulate the expression of endomucin and
      other LSL peptide components in different phases of the menstrual cycle.

PMID- 29362382
TI  - Comparison between direct contact and extract exposure methods for PFO
      cytotoxicity evaluation.
AB  - A series of recent acute blindness cases following non-complicated retinal
      detachment surgery caused the release of several health alerts in Spain. The
      blindness was attributed to certain lots of perfluoro-octane (PFO; a volatile and
      transient medical device). Similar cases have been reported in other countries.
      This has raised questions regarding the validity of cytotoxicity test methods
      currently used to certify the safety of PFO lots. The tests were performed
      according to the International Organization for Standardization (ISO) norms,
      using the extract dilution method or the indirect contact method as applied to
      L929 cells, a line derived from mouse fibroblasts. The limitations of those
      methods have been resolved in this study by proposing a new cytotoxicity test
      method for volatile substances. The new method requires direct contact of the
      tested substance with cells that are similar to those exposed to the substance in
      the clinical setting. This approach includes a few new technical steps that are
      crucial for detecting cytotoxicity. Our new method detected toxic PFO lots that
      corresponded to the lots producing clinical blindness, which previous methods
      failed to detect. The study suggests applying this new method to avoid occurrence
      of such cases of blindness.

PMID- 29362383
TI  - Individual Variation in Social Behaviours of Male Lab-reared Prairie voles
      (Microtus ochrogaster) is Non-heritable and Weakly Associated with V1aR Density.
AB  - The genetic and environmental factors that contribute to pair bonding behaviour
      remain poorly understood. Prairie voles (Microtus ochrogaster) often, but not
      always, form stable pair bonds and present an ideal model species for
      investigating the genetic and environmental factors that influence monogamy.
      Here, we assessed variation in partner preference, a measure of pair bonding, and
      related social behaviours in a population of laboratory-reared prairie voles
      under controlled environmental conditions. We evaluated to what extent variation
      in these behaviours correlate with vasopressin 1a receptor (V1aR) expression in
      the ventral pallidum (VP) and retrosplenial cortex (RSC), and estimated the
      heritability of these behaviours and V1aR expression. We found substantial
      variation in partner preference and measures of aggression, paternal care, and
      anxiety-like behaviours, but no correlation between these traits. We also found
      variation in V1aR density in the VP and RSC can account for behavioural
      components of paternal care and aggression, but not in partner preference.
      Heritability estimates of variation in partner preference were low, yet
      heritability estimates for V1aR expression were high, indicating that the
      extensive variation in partner preference observed within this population is due
      largely to environmental plasticity.

PMID- 29362384
TI  - Electrochemical Evaluation and Phase-related Impedance Studies on Silicon-Few
      Layer Graphene (FLG) Composite Electrode Systems.
AB  - Silicon-Few Layer Graphene (Si-FLG) composite electrodes are investigated using a
      scalable electrode manufacturing method. A comprehensive study on the
      electrochemical performance and the impedance response is measured using
      electrochemical impedance spectroscopy. The study demonstrates that the
      incorporation of few-layer graphene (FLG) results in significant improvement in
      terms of cyclability, electrode resistance and diffusion properties.
      Additionally, the diffusion impedance responses that occur during the phase
      changes in silicon is elucidated through Staircase Potentio Electrochemical
      Impedance Spectroscopy (SPEIS): a more comprehensive and straightforward approach
      than previous state-of-charge based diffusion studies.

PMID- 29362385
TI  - A systematic review and meta-analysis: Association between MGMT hypermethylation
      and the clinicopathological characteristics of non-small-cell lung carcinoma.
AB  - The relationship between O-6-methylguanine-DNA methyltransferase (MGMT) promoter
      methylation and clinicopathological characteristics of non-small-cell lung
      carcinoma (NSCLC) has remained controversial and unclear. Therefore, in this
      study we have undertaken a systematic review and meta-analysis of relevant
      studies to quantitatively investigate this association. We identified 30 eligible
      studies investigating 2714 NSCLC patients. The relationship between MGMT
      hypermethylation and NSCLC was identified based on 20 studies, including 1539
      NSCLC patient tissue and 1052 normal and adjacent tissue samples (OR = 4.60, 95%
      CI = 3.46~6.11, p < 0.00001). MGMT methylation varied with ethnicity (caucasian:
      OR = 4.56, 95% CI = 2.63~7.92, p < 0.00001; asian: OR = 5.18, 95% CI =
      2.03~13.22, p = 0.0006) and control style (autologous: OR = 4.44, 95% CI =
      3.32~5.92, p < 0.00001; heterogeneous: OR = 9.05, 95% CI = 1.79~45.71, p =
      0.008). In addition, MGMT methylation was observed to be specifically associated
      with NSCLC clinical stage, and not with age, sex, smoking, pathological types,
      and differentiation status. Also MGMT methylation did not impact NSCLC patients
      survival (HR = 1.32, 95% CI = 0.77~2.28, p = 0.31). Our study provided clear
      evidence about the association of MGMT hypermethylation with increased risk of
      NSCLC.

PMID- 29362386
TI  - 3-D micro-architecture and mechanical response of soil cemented via microbial
      induced calcite precipitation.
AB  - We introduce the application of microbial-induced calcite precipitation via the
      ureolytic soil bacterium Sporosarcina Pasteurii in freeze-dried form, as a means
      of enhancing overall MICP efficiency and reproducibility for geotechnical
      engineering applications. We show that the execution of urea hydrolysis and CaCO3
      precipitation persist as a "cell-free" mechanism upon the complete breakdown of
      rehydrated cell clusters. Further, strength and stiffness parameters of bio
      cemented sands are determined. Medium-grained bio-cemented sand yields
      compressive strengths up to 12 MPa while, surprisingly, fine-grained sand yields
      up to 2.5 MPa for similar bond contents. To understand the observed
      discrepancies, we undertake a systematic study of the bio-cemented material's
      microstructure, by combining a series of microstructural inspection tools. The
      study extends beyond conventional qualitative and textural characterization and
      provides with new insight into the material's peculiar 3D micro-architecture. We
      apply a new methodology towards quantifying crucial microscopic characteristics
      such as the particle sizes of the crystalline bond lattice, the bond-grain
      contacts and particle orientations. Bonds are found to exhibit distinctive
      geometries and morphologies when MICP applies to different base materials. We
      thus contribute to the debate on the importance of factors affecting: (i) MICP
      efficiency, (ii) the mechanical response and (iii) peculiar micro-architecture of
      bio-improved geo-materials.

PMID- 29362387
TI  - Effects of ambroxol on the autophagy-lysosome pathway and mitochondria in primary
      cortical neurons.
AB  - Glucocerebrosidase (GBA1) mutations are the major genetic risk factor for
      Parkinson's Disease (PD). The pathogenic mechanism is still unclear, but
      alterations in lysosomal-autophagy processes are implicated due to reduction of
      mutated glucocerebrosidase (GCase) in lysosomes. Wild-type GCase activity is also
      decreased in sporadic PD brains. Small molecule chaperones that increase
      lysosomal GCase activity have potential to be disease-modifying therapies for
      GBA1-associated and sporadic PD. Therefore we have used mouse cortical neurons to
      explore the effects of the chaperone ambroxol. This chaperone increased wild-type
      GCase mRNA, protein levels and activity, as well as increasing other lysosomal
      enzymes and LIMP2, the GCase transporter. Transcription factor EB (TFEB), the
      master regulator of the CLEAR pathway involved in lysosomal biogenesis was also
      increased upon ambroxol treatment. Moreover, we found macroautophagy flux blocked
      and exocytosis increased in neurons treated with ambroxol. We suggest that
      ambroxol is blocking autophagy and driving cargo towards the secretory pathway.
      Mitochondria content was also found to be increased by ambroxol via peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha (PGC1-alpha). Our data
      suggest that ambroxol, besides being a GCase chaperone, also acts on other
      pathways, such as mitochondria, lysosomal biogenesis, and the secretory pathway.

PMID- 29362388
TI  - Drylands soil bacterial community is affected by land use change and different
      irrigation practices in the Mezquital Valley, Mexico.
AB  - Dryland agriculture nourishes one third of global population, although crop
      irrigation is often mandatory. As freshwater sources are scarce, treated and
      untreated wastewater is increasingly used for irrigation. Here, we investigated
      how the transformation of semiarid shrubland into rainfed farming or irrigated
      agriculture with freshwater, dam-stored or untreated wastewater affects the total
      (DNA-based) and active (RNA-based) soil bacterial community composition,
      diversity, and functionality. To do this we collected soil samples during the dry
      and rainy seasons and isolated DNA and RNA. Soil moisture, sodium content and pH
      were the strongest drivers of the bacterial community composition. We found
      lineage-specific adaptations to drought and sodium content in specific land use
      systems. Predicted functionality profiles revealed gene abundances involved in
      nitrogen, carbon and phosphorous cycles differed among land use systems and
      season. Freshwater irrigated bacterial community is taxonomically and
      functionally susceptible to seasonal environmental changes, while wastewater
      irrigated ones are taxonomically susceptible but functionally resistant to them.
      Additionally, we identified potentially harmful human and phytopathogens. The
      analyses of 16 S rRNA genes, its transcripts and deduced functional profiles
      provided extensive understanding of the short-term and long-term responses of
      bacterial communities associated to land use, seasonality, and water quality used
      for irrigation in drylands.

PMID- 29362389
TI  - Capturing expert uncertainty in spatial cumulative impact assessments.
AB  - Understanding the spatial distribution of human impacts on marine environments is
      necessary for maintaining healthy ecosystems and supporting 'blue economies'.
      Realistic assessments of impact must consider the cumulative impacts of multiple,
      coincident threats and the differing vulnerabilities of ecosystems to these
      threats. Expert knowledge is often used to assess impact in marine ecosystems
      because empirical data are lacking; however, this introduces uncertainty into the
      results. As part of a spatial cumulative impact assessment for Spencer Gulf,
      South Australia, we asked experts to estimate score ranges (best-case, most
      likely and worst-case), which accounted for their uncertainty about the effect of
      32 threats on eight ecosystems. Expert scores were combined with data on the
      spatial pattern and intensity of threats to generate cumulative impact maps based
      on each of the three scoring scenarios, as well as simulations and maps of
      uncertainty. We compared our method, which explicitly accounts for the experts'
      knowledge-based uncertainty, with other approaches and found that it provides
      smaller uncertainty bounds, leading to more constrained assessment results.
      Collecting these additional data on experts' knowledge-based uncertainty provides
      transparency and simplifies interpretation of the outputs from spatial cumulative
      impact assessments, facilitating their application for sustainable resource
      management and conservation.

PMID- 29362390
TI  - Effect of Salt Intake on Plasma and Urinary Uric Acid Levels in Chinese Adults:
      An Interventional Trial.
AB  - Uric acid (UA) has been proposed as an important risk factor for cardiovascular
      and renal morbidity. We conducted an interventional trial to assess effects of
      altered salt intake on plasma and urine UA levels and the relationship between UA
      levels and salt sensitivity in humans. Ninety subjects (18-65 years old) were
      sequentially maintained on a normal diet for 3 days at baseline, a low-salt diet
      for 7 days (3.0 g/day, NaCl), and a high-salt diet for an additional 7 days (18.0
      g/day of NaCl). Plasma UA levels significantly increased from baseline to low
      salt diet and decreased from low-salt to high-salt diet. By contrast, daily
      urinary levels of UA significantly decreased from baseline to low-salt diet and
      increased from low-salt to high-salt diet. The 24 h urinary sodium excretions
      showed inverse correlation with plasma UA and positive correlation with urinary
      UA excretions. Additionally, salt-sensitive subjects presented significantly
      higher plasma UA changes in comparison to salt-resistant subjects, and a negative
      correlation was observed between degree of salt sensitivity and plasma UA
      difference. The present study indicates that variations in dietary salt intake
      affect plasma and urine UA levels, and plasma UA may be involved in
      pathophysiological process of salt sensitivity.

PMID- 29362391
TI  - Widespread modulation of gene expression by copy number variation in skeletal
      muscle.
AB  - Copy number variation (CNV) is a frequently observed deviation from the diploid
      state due to duplication or deletion of genomic regions. Although intensively
      analyzed for association with diseases and production traits, the specific
      mechanisms and extent by which such variations affect the phenotype are
      incompletely understood. We present an integrative study on CNV and genome-wide
      gene expression in Brazilian Bos indicus cattle. We analyzed CNVs inferred from
      SNP-chip data for effects on gene expression measured with RNA-seq in skeletal
      muscle samples of 183 steers. Local effects, where expression changes coincided
      with CNVs in the respective genes, were restricted to immune genes. Distal
      effects were attributable to several high-impact CNVs that modulated remote
      expression in an orchestrated and intertwined fashion. These CNVs were located in
      the vicinity of major skeletal muscle pathway regulators and associated genes
      were enriched for proteolysis, autophagy, and muscle structure development. From
      association analysis between CNVs and several meat quality and production traits,
      we found CNV-associated expression effects to also manifest at the phenotype
      level. Based on genome sequences of the population founders, we further
      demonstrate that CNVs with impact on expression and phenotype are passed on from
      one generation to another.

PMID- 29362393
TI  - Rapid Growth of Nanocrystalline Diamond on Single Crystal Diamond for Studies on
      Materials under Extreme Conditions.
AB  - Early stage nucleation morphologies of spatially localized nanocrystalline
      diamond (NCD) micro-anvils grown on (100)-oriented single crystal diamond (SCD)
      anvil surfaces were analyzed and investigated for applications in high pressure
      studies on materials. NCD was grown on SCD using Microwave Plasma Chemical Vapor
      Deposition (MPCVD) for brief time intervals ranging from 1-15 minutes. Early
      stage film morphologies were characterized using scanning electron microscopy
      (SEM) and Raman spectroscopy and were compared to films grown for several hours.
      Rapid nucleation and growth of NCD on SCD is demonstrated without any pre-growth
      seeding of the substrate surface. As grown NCD diamond micro-anvils on SCD were
      used to generate static pressure of 0.5 Terapascal (TPa) on a tungsten sample as
      measured by synchrotron x-ray diffraction in a diamond anvil cell. Atomic force
      microscopy (AFM) analysis after decompression from ultrahigh pressures showed
      that the detachment of the NCD stage occurred in the bulk of the SCD and not at
      the interface, suggesting significant adhesive bond strength between
      nanocrystalline and single crystal diamond.

PMID- 29362392
TI  - Premature polyadenylation of MAGI3 is associated with diminished N6
      methyladenosine in its large internal exon.
AB  - In cancer, tumor suppressor genes (TSGs) are frequently truncated, causing their
      encoded products to be non-functional or dominant-negative. We previously showed
      that premature polyadenylation (pPA) of MAGI3 truncates the gene, switching its
      functional role from a TSG to a dominant-negative oncogene. Here we report that
      MAGI3 undergoes pPA at the intron immediately downstream of its large internal
      exon, which is normally highly modified by N6-methyladenosine (m6A). In breast
      cancer cells that upregulate MAGI3 pPA , m6A levels in the large internal exon of
      MAGI3 are significantly reduced compared to cells that do not express MAGI3 pPA .
      We further find that MAGI3 pPA transcripts are significantly depleted of m6A
      modifications, in contrast to highly m6A-modified full-length MAGI3 mRNA.
      Finally, we analyze public expression data and find that other TSGs, including
      LATS1 and BRCA1, also undergo intronic pPA following large internal exons, and
      that m6A levels in these exons are reduced in pPA-activated breast cancer cells
      relative to untransformed mammary cells. Our study suggests that m6A may play a
      role in regulating intronic pPA of MAGI3 and possibly other TSGs, warranting
      further investigation.

PMID- 29362394
TI  - Improvement in creep life of a nickel-based single-crystal superalloy via
      composition homogeneity on the multiscales by magnetic-field-assisted directional
      solidification.
AB  - The improvement of the creep properties of single-crystal superalloys is always
      strongly motivated by the vast growing demand from the aviation, aerospace, and
      gas engine. In this study, a static magnetic-field-assisted solidification
      process significantly improves the creep life of single-crystal superalloys. The
      mechanism originates from an increase in the composition homogeneity on the
      multiscales, which further decreases the lattice misfit of gamma/gamma' phases
      and affects the phase precipitation. The phase-precipitation change is reflected
      as the decrease in the gamma' size and the contents of carbides and gamma/gamma'
      eutectic, which can be further verified by the variation of the cracks number and
      raft thickness near the fracture surface. The variation of element partition
      decreases the dislocation quantity within the gamma/gamma' phases of the samples
      during the crept deformation. Though the magnetic field in the study destroys the
      single-crystal integrity, it does not offset the benefits from the compositional
      homogeneity. The proposed means shows a great potential application in industry
      owing to its easy implement. The uncovered mechanism provides a guideline for
      controlling microstructures and mechanical properties of alloys with multiple
      components and multiple phases using a magnetic field.

PMID- 29362396
TI  - Geographically weighted temporally correlated logistic regression model.
AB  - Detecting the temporally and spatially varying correlations is important to
      understand the biological and disease systems. Here we proposed a geographically
      weighted temporally correlated logistic regression (GWTCLR) model to identify
      such dynamic correlation of predictors on binomial outcome data, by incorporating
      spatial and temporal information for joint inference. The local likelihood method
      is adopted to estimate the spatial relationship, while the smoothing method is
      employed to estimate the temporal variation. We present the construction and
      implementation of GWTCLR and the study of the asymptotic properties of the
      proposed estimator. Simulation studies were conducted to evaluate the robustness
      of the proposed model. GWTCLR was applied on real epidemiologic data to study the
      climatic determinants of human seasonal influenza epidemics. Our method obtained
      results largely consistent with previous studies but also revealed certain
      spatial and temporal varying patterns that were unobservable by previous models
      and methods.

PMID- 29362395
TI  - Chitin digestibility is dependent on feeding behaviors, which determine acidic
      chitinase mRNA levels in mammalian and poultry stomachs.
AB  - Chitin, a polymer of N-acetyl-D-glucosamine (GlcNAc), functions as a major
      structural component in chitin-containing organism including crustaceans, insects
      and fungi. Recently, we reported that acidic chitinase (Chia) is highly expressed
      in mouse, chicken and pig stomach tissues and that it can digest chitin in the
      respective gastrointestinal tracts (GIT). In this study, we focus on major
      livestock and domestic animals and show that the levels of Chia mRNA in their
      stomach tissues are governed by the feeding behavior. Chia mRNA levels were
      significantly lower in the bovine (herbivores) and dog (carnivores) stomach than
      those in mouse, pig and chicken (omnivores). Consistent with the mRNA levels,
      Chia protein was very low in bovine stomach. In addition, the chitinolytic
      activity of E. coli-expressed bovine and dog Chia enzymes were moderately but
      significantly lower compared with those of the omnivorous Chia enzymes.
      Recombinant bovine and dog Chia enzymes can degrade chitin substrates under the
      artificial GIT conditions. Furthermore, genomes of some herbivorous animals such
      as rabbit and guinea pig do not contain functional Chia genes. These results
      indicate that feeding behavior affects Chia expression levels as well as
      chitinolytic activity of the enzyme, and determines chitin digestibility in the
      particular animals.

PMID- 29362399
TI  - Companion diagnostics: new opportunities for safe and effective anti-infectious
      disease therapies.

PMID- 29362397
TI  - Glutathione transferases: substrates, inihibitors and pro-drugs in cancer and
      neurodegenerative diseases.
AB  - Glutathione transferase classical GSH conjugation activity plays a critical role
      in cellular detoxification against xenobiotics and noxious compounds as well as
      against oxidative stress. However, this feature is also exploited by cancer cells
      to acquire drug resistance and improve their survival. As a result, various
      members of the family were found overexpressed in a number of different cancers.
      Moreover several GST polymorphisms, ranging from null phenotypes to point
      mutations, were detected in members of the family and found to correlate with the
      onset of neuro-degenerative diseases. In the last decades, a great deal of
      research aimed at clarifying the role played by GSTs in drug resistance, at
      developing inhibitors to counteract this activity but also at exploiting GSTs for
      prodrugs specific activation in cancer cells. Here we summarize some of the most
      important achievements reached in this lively area of research.

PMID- 29362398
TI  - A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes
      ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway.
AB  - Ruthenium-based compounds have gained great interest due to their potent
      cytotoxicity in cancer cells; however, much of their potential applications
      remain unexplored. In this paper, we report the synthesis of a novel ruthenium
      complex with xanthoxylin (RCX) and the investigation of its cellular and
      molecular action in human hepatocellular carcinoma HepG2 cells. We found that RCX
      exhibited a potent cytotoxic effect in a panel of cancer cell lines in monolayer
      cultures and in a 3D model of multicellular cancer spheroids formed from HepG2
      cells. This compound is detected at a high concentration in the cell nuclei,
      induces DNA intercalation and inhibits DNA synthesis, arresting the cell cycle in
      the S-phase, which is followed by the activation of the caspase-mediated
      apoptosis pathway in HepG2 cells. Gene expression analysis revealed changes in
      the expression of genes related to cell cycle control, apoptosis and the MAPK
      pathway. In addition, RCX induced the phosphorylation of ERK1/2, and pretreatment
      with U-0126, an MEK inhibitor known to inhibit the activation of ERK1/2,
      prevented RCX-induced apoptosis. In contrast, pretreatment with a p53 inhibitor
      (cyclic pifithrin-alpha) did not prevent RCX-induced apoptosis, indicating the
      activation of a p53-independent apoptosis pathway. RCX also presented a potent in
      vivo antitumor effect in C.B-17 SCID mice engrafted with HepG2 cells. Altogether,
      these results indicate that RCX is a novel anticancer drug candidate.

PMID- 29362400
TI  - Genetics, pathogenicity and transmissibility of novel reassortant H5N6 highly
      pathogenic avian influenza viruses first isolated from migratory birds in western
      China.

PMID- 29362401
TI  - MicroRNA miR-4779 suppresses tumor growth by inducing apoptosis and cell cycle
      arrest through direct targeting of PAK2 and CCND3.
AB  - Depending on the function of their target genes, microRNAs (miRNAs) act as either
      tumor suppressors or oncogenes. Therefore, miRNAs represent a novel therapeutic
      strategy for prevention and management of cancer by targeting of onco-miRNAs or
      mimicking of tumor suppressor miRNAs. Herein, we identified novel tumor
      suppressor miRNAs and investigated their molecular mechanisms. To identify novel
      tumor suppressor miRNAs, we used 532 human miRNA mimic libraries and measured
      cell viability using MTS assays. The function of miR-4779 was then analyzed using
      cell cycle analyses and apoptosis, colony forming, and soft agar assays. Target
      genes of miR-4779 were predicted using TargetScan and miRDB databases and were
      confirmed using luciferase assays. Levels of miR-4779 and target genes in colon
      cancer tissue samples from patients were evaluated using qRT-PCR and western
      blotting analyses. Finally, in vivo tumor suppressive effects of miR-4779 were
      evaluated in HCT116 xenografts. In this study, miR-4779 inhibited cancer cell
      growth by inducing apoptosis and cell cycle arrest, and the putative survival
      factors PAK2 and CCND3 were identified as direct targets of miR-4779. In
      subsequent experiments, PAK2 knockdown induced cell cycle arrest and CCND3
      knockdown induced cell cycle arrest and apoptosis. In addition, miR-4779
      suppressed tumor growth and tumorigenesis in an in vivo HCT116 xenograft model.
      Finally, miR-4779 expression was low in 9 of 10 colon cancer tissues, whereas
      PAK2 and CCND3 expressions were significantly high in colon cancer tissues. The
      novel tumor suppressor miR-4779 inhibits cancer cell growth via cell cycle arrest
      and apoptosis by directly targeting PAK2 and CCND3. The present data indicate the
      potential of miR-4779 as a therapeutic target for miRNA-based cancer therapy.

PMID- 29362403
TI  - Publisher Correction: Freeform micropatterning of living cells into cell culture
      medium using direct inkjet printing.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29362404
TI  - Sequence-regulated copolymerization based on periodic covalent positioning of
      monomers along one-dimensional nanochannels.
AB  - The design of monomer sequences in polymers has been a challenging research
      subject, especially in making vinyl copolymers by free-radical polymerization.
      Here, we report a strategy to obtain sequence-regulated vinyl copolymers,
      utilizing the periodic structure of a porous coordination polymer (PCP) as a
      template. Mixing of Cu2+ ion and styrene-3,5-dicarboxylic acid (S) produces a
      PCP, [Cu(styrene-3,5-dicarboxylate)] n , with the styryl groups periodically
      immobilized along the one-dimensional channels. After the introduction of
      acrylonitrile (A) into the host PCP, radical copolymerization between A and the
      immobilized S is performed inside the channel, followed by decomposing the PCP to
      isolate the resulting copolymer. The predominant repetitive SAAA sequence in the
      copolymer is confirmed by monomer composition, NMR spectroscopy and theoretical
      calculations. Copolymerization using methyl vinyl ketone also provides the same
      type of sequence-regulated copolymer, showing that this methodology has a
      versatility to control the copolymer sequence via transcription of PCP
      periodicity at the molecular level.

PMID- 29362402
TI  - The hypoxic tumour microenvironment.
AB  - Cancer progression often benefits from the selective conditions present in the
      tumour microenvironment, such as the presence of cancer-associated fibroblasts
      (CAFs), deregulated ECM deposition, expanded vascularisation and repression of
      the immune response. Generation of a hypoxic environment and activation of its
      main effector, hypoxia-inducible factor-1 (HIF-1), are common features of
      advanced cancers. In addition to the impact on tumour cell biology, the influence
      that hypoxia exerts on the surrounding cells represents a critical step in the
      tumorigenic process. Hypoxia indeed enables a number of events in the tumour
      microenvironment that lead to the expansion of aggressive clones from
      heterogeneous tumour cells and promote a lethal phenotype. In this article, we
      review the most relevant findings describing the influence of hypoxia and the
      contribution of HIF activation on the major components of the tumour
      microenvironment, and we summarise their role in cancer development and
      progression.

PMID- 29362405
TI  - Transcriptional profiling of long non-coding RNAs in mantle of Crassostrea gigas
      and their association with shell pigmentation.
AB  - Long non-coding RNAs (lncRNAs) play crucial roles in diverse biological processes
      and have drawn extensive attention in the past few years. However, lncRNAs remain
      poorly understood about expression and roles in Crassostrea gigas, a potential
      model organism for marine molluscan studies. Here, we systematically identified
      lncRNAs in the mantles of C. gigas from four full-sib families characterized by
      white, black, golden, and partially pigmented shell. Using poly(A)-independent
      and strand-specific RNA-seq, a total of 441,205,852 clean reads and 12,243 lncRNA
      transcripts were obtained. LncRNA transcripts were relatively short with few
      exons and low levels of expression in comparison to protein coding mRNA
      transcripts. A total of 427 lncRNAs and 349 mRNAs were identified to
      differentially express among six pairwise groups, mainly involving in
      biomineralization and pigmentation through functional enrichment. Furthermore, a
      total of 6 mRNAs and their cis-acting lncRNAs were predicted to involve in
      synthesis of melanin, carotenoid, tetrapyrrole, or ommochrome. Of them, chorion
      peroxidase and its cis-acting lincRNA TCONS_00951105 are implicated in playing an
      essential role in the melanin synthetic pathway. Our studies provided the first
      systematic characterization of lncRNAs catalog expressed in oyster mantle, which
      may facilitate understanding the molecular regulation of shell colour diversity
      and provide new insights into future selective breeding of C. gigas for
      aquaculture.

PMID- 29362407
TI  - Publisher Correction: Circadian preference towards morningness is associated with
      lower slow sleep spindle amplitude and intensity in adolescents.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29362406
TI  - Epidemiological and serological surveillance of hand-foot-and-mouth disease in
      Shanghai, China, 2012-2016.
AB  - Aside from enterovirus 71 (EV71) and coxsackie virus A16 (CV-A16), viruses that
      are known to cause hand-foot-and-mouth disease (HFMD), epidemiological profiles
      of other enteroviruses that induce HFMD are limited. We collected 9949 laboratory
      surveillance HFMD cases and 1230 serum samples from infants and children in
      Shanghai from 2012-2016. Since 2013, CV-A6 has displaced EV71 and CV-A16 to
      become the predominant serotype. Interestingly, novel epidemiological patterns in
      EV71 and CV-A16 infections were observed, with one large peak in both 2012 and
      2014, followed by two smaller peaks in the respective following years (2013 and
      2015). Through sequencing, we found that C4a, B1b, D-Cluster-1 and B constituted
      the major subgenotypes of EV71, CV-A16, CV-A6 and CV-A10, respectively. Among
      healthy individuals, 50.49% and 54.23% had positive neutralising antibodies
      (NtAbs) against EV71 and CV-A16, respectively, indicating that EV71 and CV-A16
      silent infections were common. These populations may be an important potential
      source of infection. The overall seropositive rate of EV71 NtAbs showed a
      fluctuating, markedly downward trend, indicating the potential risk of a future
      EV71 epidemic. High CV-A16 NtAb seroprevalence corroborated a documented CV-A16
      'silent' epidemic. Children aged 1-5 years had the lowest EV71 NtAb seropositive
      rate, whereas those aged 1-2 years exhibited the lowest CV-A16 NtAb seropositive
      rate. This is the first comprehensive investigation of the epidemiology and
      aetiology, as well as the seroprevalence, of HFMD in Shanghai between 2012 and
      2016. This study provides the latest insights into developing a more efficient
      HMFD vaccination programme.

PMID- 29362408
TI  - Attentional and physiological processing of food images in functional dyspepsia
      patients: A pilot study.
AB  - The food-related behavior of functional dyspepsia has been attracting more
      interest of late. This pilot study aims to provide evidence of the physiological,
      emotional, and attentional aspects of food processing in functional dyspepsia
      patients. The study was performed in 15 functional dyspepsia patients and 17
      healthy controls after a standard breakfast. We measured autonomic nervous system
      activity using skin conductance response and heart rate variability, emotional
      response using facial electromyography, and visual attention using eyetracking
      during the visual stimuli of food/non-food images. In comparison to healthy
      controls, functional dyspepsia patients showed a greater craving for food, a
      decreased intake of food, more dyspeptic symptoms, lower pleasantness rating of
      food images (particularly of high fat), decreased low frequency/high frequency
      ratio of heart rate variability, and suppressed total processing time of food
      images. There were no significant differences of skin conductance response and
      facial electromyography data between groups. The results suggest that high level
      cognitive functions rather than autonomic and emotional mechanisms are more
      liable to function differently in functional dyspepsia patients. Abnormal dietary
      behavior, reduced subjective rating of pleasantness and visual attention to food
      should be considered as important pathophysiological characteristics in
      functional dyspepsia.

PMID- 29362409
TI  - Cancer cell-derived von Willebrand factor enhanced metastasis of gastric
      adenocarcinoma.
AB  - Cancer prognosis is poor for patients with blood-borne metastasis. Platelets are
      known to assist cancer cells in transmigrating through the endothelium, but
      ligands for the platelet-mediated cancer metastasis remain poorly defined. von
      Willebrand factor (vWF) is a major platelet ligand that has been widely used as a
      biomarker in cancer and associated inflammation. However, its functional role in
      cancer growth and metastasis is largely unknown. Here we report that gastric
      cancer cells from patients and cells from two well-established gastric cancer
      lines express vWF and secrete it into the circulation, upon which it rapidly
      becomes cell-bound to mediate cancer-cell aggregation and interaction with
      platelets and endothelial cells. The vWF-mediated homotypic and heterotypic cell
      cell interactions promote the pulmonary graft of vWF-overexpressing gastric
      cancer BGC823 cells in a mouse model. The metastasis-promoting activity of vWF
      was blocked by antibodies against vWF and its platelet receptor GP Ibalpha. It
      was also reduced by an inhibitory siRNA that suppresses vWF expression. These
      findings demonstrate a causal role of cancer-cell-derived vWF in mediating
      gastric cancer metastasis and identify vWF as a new therapeutic target.

PMID- 29362411
TI  - Growth of magnetic nanowires along freely selectable <hkl> crystal directions.
AB  - The production of nanowire materials, uniformly oriented along any arbitrarily
      chosen crystal orientation, is an important, yet unsolved, problem in material
      science. Here, we present a generalizable solution to this problem. The solution
      is based on the technique of glancing angle deposition combined with a rapid
      switching of the deposition direction between crystal symmetry positions. Using
      iron-cobalt as an example, we showcase the simplicity and capabilities of the
      process in one-step fabrications of <100>, <110>, <111>, <210>, <310>, <320>, and
      <321>-oriented nanowires, three-dimensional nanowire spirals, core-shell
      heterostructures, and axial hybrids. Our results provide a new capability for
      tailoring the properties of nanowires, and should be generalizable to any
      material that can be grown as a single-crystal biaxial film.

PMID- 29362410
TI  - New live screening of plant-nematode interactions in the rhizosphere.
AB  - Free living nematodes (FLN) are microscopic worms found in all soils. While many
      FLN species are beneficial to crops, some species cause significant damage by
      feeding on roots and vectoring viruses. With the planned legislative removal of
      traditionally used chemical treatments, identification of new ways to manage FLN
      populations has become a high priority. For this, more powerful screening systems
      are required to rapidly assess threats to crops and identify treatments
      efficiently. Here, we have developed new live assays for testing nematode
      responses to treatment by combining transparent soil microcosms, a new light
      sheet imaging technique termed Biospeckle Selective Plane Illumination Microscopy
      (BSPIM) for fast nematode detection, and Confocal Laser Scanning Microscopy for
      high resolution imaging. We show that BSPIM increased signal to noise ratios by
      up to 60 fold and allowed the automatic detection of FLN in transparent soil
      samples of 1.5 mL. Growing plant root systems were rapidly scanned for nematode
      abundance and activity, and FLN feeding behaviour and responses to chemical
      compounds observed in soil-like conditions. This approach could be used for
      direct monitoring of FLN activity either to develop new compounds that target
      economically damaging herbivorous nematodes or ensuring that beneficial species
      are not negatively impacted.

PMID- 29362412
TI  - Consensus Clustering of temporal profiles for the identification of metabolic
      markers of pre-diabetes in childhood (EarlyBird 73).
AB  - In longitudinal clinical studies, methodologies available for the analysis of
      multivariate data with multivariate methods are relatively limited. Here, we
      present Consensus Clustering (CClust) a new computational method based on
      clustering of time profiles and posterior identification of correlation between
      clusters and predictors. Subjects are first clustered in groups according to a
      response variable temporal profile, using a robust consensus-based strategy. To
      discover which of the remaining variables are associated with the resulting
      groups, a non-parametric hypothesis test is performed between groups at every
      time point, and then the results are aggregated according to the Fisher method.
      Our approach is tested through its application to the EarlyBird cohort database,
      which contains temporal variations of clinical, metabolic, and anthropometric
      profiles in a population of 150 children followed-up annually from age 5 to age
      16. Our results show that our consensus-based method is able to overcome the
      problem of the approach-dependent results produced by current clustering
      algorithms, producing groups defined according to Insulin Resistance (IR) and
      biological age (Tanner Score). Moreover, it provides meaningful biological
      results confirmed by hypothesis testing with most of the main clinical variables.
      These results position CClust as a valid alternative for the analysis of
      multivariate longitudinal data.

PMID- 29362413
TI  - Spin Hall photoconductance in a three-dimensional topological insulator at room
      temperature.
AB  - Three-dimensional topological insulators are a class of Dirac materials, wherein
      strong spin-orbit coupling leads to two-dimensional surface states. The latter
      feature spin-momentum locking, i.e., each momentum vector is associated with a
      spin locked perpendicularly to it in the surface plane. While the principal spin
      generation capability of topological insulators is well established,
      comparatively little is known about the interaction of the spins with external
      stimuli like polarized light. We observe a helical, bias-dependent
      photoconductance at the lateral edges of topological Bi2Te2Se platelets for
      perpendicular incidence of light. The same edges exhibit also a finite bias
      dependent Kerr angle, indicative of spin accumulation induced by a transversal
      spin Hall effect in the bulk states of the Bi2Te2Se platelets. A symmetry
      analysis shows that the helical photoconductance is distinct to common
      longitudinal photoconductance and photocurrent phenomena, but consistent with
      optically injected spins being transported in the side facets of the platelets.

PMID- 29362414
TI  - Transalveolar sinus floor lift without bone grafting in atrophic maxilla: A meta
      analysis.
AB  - We performed a meta-analysis aimed to assess the clinical results after
      transalveolar sinus floor lift without bone grafting in the atrophic maxilla. A
      systematic electronic literature search was conducted in PubMed, Embase and The
      Cochrane Library, followed by a manual search. Two reviewers independently
      extracted study data and conducted quality assessments. Ten non-controlled
      studies including 1484 implants and eight controlled studies (5 RCTs and 3
      prospective studies) including 817 implants (451 implants in the non-graft group)
      were enrolled in this study. The survival rate of implants via the graft-free
      method was 98% (95%CI 96% to 100%). There was no significant difference in the
      survival rate between the non-graft group and the graft group (RR: 1.02; p =
      0.18). No statistically significant difference in marginal bone loss was detected
      between the groups at 12 months (0.57, p = 0.07) or 36 months (0.05, p = 0.61).
      The endo-sinus bone gain in the non-graft group was significantly lower than in
      the graft group at 12 months (-1.10, p = 0.0001) and 36 months (-0.74, p = 0.02).
      Hence, the available evidence suggests that predictable results could be acquired
      through transalveolar sinus floor lift without bone grafting, while there may be
      a trend toward more endo-sinus bone gain with bone grafts.

PMID- 29362415
TI  - A Necessary and Sufficient Criterion for the Separability of Quantum State.
AB  - Quantum entanglement has been regarded as one of the key physical resources in
      quantum information sciences. However, the determination of whether a mixed state
      is entangled or not is generally a hard issue, even for the bipartite system. In
      this work we propose an operational necessary and sufficient criterion for the
      separability of an arbitrary bipartite mixed state, by virtue of the
      multiplicative Horn's problem. The work follows the work initiated by Horodecki
      et al. and uses the Bloch vector representation introduced to the separability
      problem by J. De Vicente. In our criterion, a complete and finite set of
      inequalities to determine the separability of compound system is obtained, which
      may be viewed as trade-off relations between the quantumness of subsystems. We
      apply the obtained result to explicit examples, e.g. the separable decomposition
      of arbitrary dimension Werner state and isotropic state.

PMID- 29362416
TI  - CREB-binding protein plays key roles in juvenile hormone action in the red flour
      beetle, Tribolium Castaneum.
AB  - Juvenile hormones (JH) and ecdysteroids regulate many biological and metabolic
      processes. CREB-binding protein (CBP) is a transcriptional co-regulator with
      histone acetyltransferase (HAT) activity. Therefore, CBP is involved in
      activation of many transcription factors that regulate expression of genes
      associated with postembryonic development in insects. However, the function of
      CBP in JH action in insects is not well understood. Hence, we studied the role of
      CBP in JH action in the red flour beetle, Tribolium castaneum and the Tribolium
      cell line. CBP knockdown caused a decrease in JH induction of genes, Kr-h1, 4EBP
      and G13402 in T. castaneum larvae, adults and TcA cells whereas, Trichostatin A
      [TSA, a histone deacetylase (HDAC) inhibitor] induced the expression of these JH
      response genes. Western blot analysis with specific antibodies revealed the
      requirement of CBP for the acetylation of H3K18 and H3K27 in both T. castaneum
      and TcA cells. Chromatin immunoprecipitation (Chip) assays showed the importance
      of CBP-mediated acetylation of H3K27 for JH induction of Kr-h1, 4EBP, and G13402
      in TcA cells. These data suggest that CBP plays an important role in JH action in
      the model insect, T.castaneum.

PMID- 29362417
TI  - Characterization of the multimeric structure of poly(A)-binding protein on a
      poly(A) tail.
AB  - Eukaryotic mature mRNAs possess a poly adenylate tail (poly(A)), to which
      multiple molecules of poly(A)-binding protein C1 (PABPC1) bind. PABPC1 regulates
      translation and mRNA metabolism by binding to regulatory proteins. To understand
      functional mechanism of the regulatory proteins, it is necessary to reveal how
      multiple molecules of PABPC1 exist on poly(A). Here, we characterize the
      structure of the multiple molecules of PABPC1 on poly(A), by using transmission
      electron microscopy (TEM), chemical cross-linking, and NMR spectroscopy. The TEM
      images and chemical cross-linking results indicate that multiple PABPC1 molecules
      form a wormlike structure in the PABPC1-poly(A) complex, in which the PABPC1
      molecules are linearly arrayed. NMR and cross-linking analyses indicate that
      PABPC1 forms a multimer by binding to the neighbouring PABPC1 molecules via
      interactions between the RNA recognition motif (RRM) 2 in one molecule and the
      middle portion of the linker region of another molecule. A PABPC1 mutant lacking
      the interaction site in the linker, which possesses an impaired ability to form
      the multimer, reduced the in vitro translation activity, suggesting the
      importance of PABPC1 multimer formation in the translation process. We therefore
      propose a model of the PABPC1 multimer that provides clues to comprehensively
      understand the regulation mechanism of mRNA translation.

PMID- 29362418
TI  - Efficient inhibition of African swine fever virus replication by CRISPR/Cas9
      targeting of the viral p30 gene (CP204L).
AB  - African swine fever is a devastating viral disease of domestic and wild pigs
      against which no vaccine or therapy is available. Therefore, we applied the
      CRISPR (clustered regularly interspaced short palindromic repeats) - Cas9
      nuclease system to target the double-stranded DNA genome of African swine fever
      virus (ASFV). To this end, a permissive wild boar lung (WSL) cell line was
      modified by stable transfection with a plasmid encoding Cas9 and a guide RNA
      targeting codons 71 to 78 of the phosphoprotein p30 gene (CP204L) of ASFV. Due to
      targeted Cas9 cleavage of the virus genome, plaque formation of ASFV was
      completely abrogated and virus yields were reduced by four orders of magnitude.
      The specificity of these effects could be demonstrated by using a natural ASFV
      isolate and escape mutants possessing nucleotide exchanges within the target
      sequence, which were not inhibited in the Cas9-expressing cell line. Growth of
      the cell line was not affected by transgene expression which, as well as virus
      inhibition, proved to be stable over at least 50 passages. Thus, CRISPR-Cas9
      mediated targeting of the ASFV p30 gene is a valid strategy to convey resistance
      against ASF infection, which may also be applied in its natural animal host.

PMID- 29362420
TI  - Low cost, microcontroller based heating device for multi-wavelength differential
      scanning fluorimetry.
AB  - Differential scanning fluorimetry is a popular method to estimate the stability
      of a protein in distinct buffer conditions by determining its 'melting point'.
      The method requires a temperature controlled fluorescence spectrometer or a RT
      PCR machine. Here, we introduce a low-budget version of a microcontroller based
      heating device implemented into a 96-well plate reader that is connected to a
      standard fluorescence spectrometer. We demonstrate its potential to determine the
      'melting point' of soluble and membranous proteins at various buffer conditions.

PMID- 29362419
TI  - Pancreatic gene expression during recovery after pancreatitis reveals unique
      transcriptome profiles.
AB  - It is well known that pancreatic recovery after a single episode of injury such
      as an isolated bout of pancreatitis occurs rapidly. It is unclear, however, what
      changes are inflicted in such conditions to the molecular landscape of the
      pancreas. In the caerulein hyperstimulation model of pancreatitis, the murine
      pancreas has the ability to recover within one week based on histological
      appearance. In this study, we sought to characterize by RNA-sequencing (RNA-seq)
      the transcriptional profile of the recovering pancreas up to two weeks post
      injury. We found that one week after injury there were 319 differentially
      expressed genes (DEGs) compared with baseline and that after two weeks there were
      53 DEGs. Forty (12.5%) of the DEGs persisted from week one to week two, and
      another 13 DEGs newly emerged in the second week. Amongst the top up-regulated
      DEGs were several trypsinogen genes (trypsinogen 4, 5, 12, 15, and 16). To our
      knowledge, this is the first characterization of the transcriptome during
      pancreatic recovery by deep sequencing, and it reveals on a molecular basis that
      there is an ongoing recovery of the pancreas even after apparent histological
      resolution. The findings also raise the possibility of an emerging novel
      transcriptome upon pancreatic recovery.

PMID- 29362421
TI  - Sporadic nesting reveals long distance colonisation in the philopatric loggerhead
      sea turtle (Caretta caretta).
AB  - The colonisation of new suitable habitats is crucial for species survival at
      evolutionary scale under changing environmental conditions. However, colonisation
      potential may be limited by philopatry that facilitates exploiting successful
      habitats across generations. We examine the mechanisms of long distance dispersal
      of the philopatric loggerhead sea turtle (Caretta caretta) by analysing 40
      sporadic nesting events in the western Mediterranean. The analysis of a fragment
      of the mitochondrial DNA and 7 microsatellites of 121 samples from 18 of these
      nesting events revealed that these nests were colonising events associated with
      juveniles from distant populations feeding in nearby foraging grounds.
      Considering the temperature-dependent sex determination of the species, we
      simulated the effect of the incubation temperature and propagule pressure on a
      potential colonisation scenario. Our results indicated that colonisation will
      succeed if warm temperature conditions, already existing in some of the beaches
      in the area, extend to the whole western Mediterranean. We hypothesize that the
      sporadic nesting events in developmental foraging grounds may be a mechanism to
      overcome philopatry limitations thus increasing the dispersal capabilities of the
      species and the adaptability to changing environments. Sporadic nesting in the
      western Mediterranean can be viewed as potential new populations in a scenario of
      rising temperatures.

PMID- 29362422
TI  - A caspase-2-RFXANK interaction and its implication for MHC class II expression.
AB  - Despite recent achievements implicating caspase-2 in tumor suppression, the
      enzyme stands out from the apoptotic caspase family as a factor whose function
      requires further clarification. To specify enzyme characteristics through the
      definition of interacting proteins in apoptotic or non-apoptotic settings, a
      yeast 2-hybrid (Y2H) screen was performed using the full-length protein as bait.
      The current report describes the analysis of a captured prey and putative novel
      caspase-2 interacting factor, the regulatory factor X-associated ankyrin
      containing protein (RFXANK), previously associated with CIITA, the transactivator
      regulating cell-type specificity and inducibility of MHC class II gene
      expression. The interaction between caspase-2 and RFXANK was verified by co
      immunoprecipitations using both exogenous and endogenous proteins, where the
      latter approach suggested that binding of the components occurs in the cytoplasm.
      Cellular co-localization was confirmed by transfection of fluorescently
      conjugated proteins. Enhanced caspase-2 processing in RFXANK-overexpressing
      HEK293T cells treated with chemotherapeutic agents further supported Y2H data.
      Yet, no distinct differences with respect to MHC class II expression were
      observed in plasma membranes of antigen-presenting cells derived from wild type
      and caspase-2-/- mice. In contrast, increased levels of the total MHC class II
      protein was evident in protein lysates from caspase-2 RNAi-silenced leukemia cell
      lines and B-cells isolated from gene-targeted mice. Together, these data identify
      a novel caspase-2-interacting factor, RFXANK, and indicate a potential non
      apoptotic role for the enzyme in the control of MHC class II gene regulation.

PMID- 29362423
TI  - Thermal Dynamics Effects using Pulse-Shaping Laser Sintering of Printed Silver
      Inks.
AB  - In recent years, additive manufacturing has been evolving towards flexible
      substrates for the fabrication of printable electronic devices and circuits.
      Generally polymer-based, these emerging substrates suffer from their heat
      sensitivity and low glass-transition temperatures. As such they require new
      highly-localized sintering processes to treat the electronic inks without
      damaging the polymer-based substrate. Laser-based sintering techniques have shown
      great promises to achieve high-quality sintering locally, while controlling the
      heat penetration to preserve the polymer substrates integrity. In this report, we
      explore new optimization pathways for dynamic laser-based sintering of conductive
      silver inks. Multiple passes of a pulsed laser are first performed while varying
      pulse train frequencies and pulse energies as an attempt to optimize the
      properties of the silver inks. Then, time-domain pulse shaping is performed to
      alter the properties of the conductive inks. Together, these pathways allow for
      the careful control of the time-domain laser energy distribution in order to
      achieve the best electronic performances while preserving the substrate's
      integrity. Sheet resistance values as low as 0.024Omega/? are achieved, which is
      comparable to conventional 1-hour oven annealing, with the processing time
      dramatically reduced to the milisecond range. These results are supported by
      finite element modeling of the laser-induced thermal dynamics.

PMID- 29362424
TI  - Functional metagenomics identifies novel genes ABCTPP, TMSRP1 and TLSRP1 among
      human gut enterotypes.
AB  - Every niche in the biosphere is touched by the seemingly endless capacity of
      microbes to transform the world around them by adapting swiftly and flexibly to
      the environmental changes, likewise the gastrointestinal tract is no exception.
      The ability to cope with rapid changes in external osmolarity is an important
      aspect of gut microbes for their survival and colonization. Identification of
      these survival mechanisms is a pivotal step towards understanding genomic
      suitability of a symbiont for successful human gut colonization. Here we
      highlight our recent work applying functional metagenomics to study human gut
      microbiome to identify candidate genes responsible for the salt stress tolerance.
      A plasmid borne metagenomic library of Bacteroidetes enriched human fecal
      metagenomic DNA led to identification of unique salt osmotolerance clones SR6 and
      SR7. Subsequent gene analysis combined with functional studies revealed that
      TLSRP1 within pSR7 and TMSRP1 and ABCTPP of pSR6 are the active loci responsible
      for osmotolerance through an energy dependent mechanism. Our study elucidates the
      novel genetic machinery involved in bestowing osmotolerance in Prevotella and
      Bacteroidetes, the predominant microbial groups in a North Indian population.
      This study unravels an alternative method for imparting ionic stress tolerance,
      which may be prevalent in the human gut microbiome.

PMID- 29362425
TI  - Group-I PAKs-mediated phosphorylation of HACE1 at serine 385 regulates its
      oligomerization state and Rac1 ubiquitination.
AB  - The regulation of Rac1 by HACE1-mediated ubiquitination and proteasomal
      degradation is emerging as an essential element in the maintenance of cell
      homeostasis. However, how the E3 ubiquitin ligase activity of HACE1 is regulated
      remains undetermined. Using a proteomic approach, we identified serine 385 as a
      target of group-I PAK kinases downstream Rac1 activation by CNF1 toxin from
      pathogenic E. coli. Moreover, cell treatment with VEGF also promotes Ser-385
      phosphorylation of HACE1. We have established in vitro that HACE1 is a direct
      target of PAK1 kinase activity. Mechanistically, we found that the phospho
      mimetic mutant HACE1(S385E), as opposed to HACE1(S385A), displays a lower
      capacity to ubiquitinate Rac1 in cells. Concomitantly, phosphorylation of Ser-385
      plays a pivotal role in controlling the oligomerization state of HACE1. Finally,
      Ser-385 phosphorylated form of HACE1 localizes in the cytosol away from its
      target Rac1. Together, our data point to a feedback inhibition of HACE1
      ubiquitination activity on Rac1 by group-I PAK kinases.

PMID- 29362426
TI  - Strength of shear bands in fluid-saturated rocks: a nonlinear effect of
      competition between dilation and fluid flow.
AB  - This study shows the significant and nonlinear effect of the competition between
      dilation and fluid flow on the shear strength of constrained shear bands in fluid
      saturated rocks. This effect is conditioned by the contribution of the pore
      pressure to the yield stress and strength. The pore pressure is controlled by the
      dilation of the pore space in the solid skeleton of the shear band during plastic
      deformation and by squeezing of pores in surrounding blocks by the dilating shear
      band due to the high stiffness of the host massif. A generalized equation has
      been derived to describe the dependence of the shear band strength on the ratio
      of strain rate to fluid flow rate.

PMID- 29362427
TI  - 3D virtual histology of murine kidneys -high resolution visualization of
      pathological alterations by micro computed tomography.
AB  - The increasing number of patients with end stage chronic kidney disease not only
      calls for novel therapeutics but also for pioneering research using convincing
      preclinical disease models and innovative analytical techniques. The aim of this
      study was to introduce a virtual histology approach using micro computed
      tomography (uCT) for the entire murine kidney in order to close the gap between
      single slice planar histology and a 3D high resolution dataset. An ex vivo
      staining protocol based on phosphotungstic acid diffusion was adapted to enhance
      renal soft tissue x-ray attenuation. Subsequent CT scans allowed (i) the
      detection of the renal cortex, medulla and pelvis in greater detail, (ii) the
      analysis of morphological alterations, (iii) the quantification of the volume as
      well as the radio-opacity of these portions and (iv) the quantification of renal
      fibrotic remodeling based on altered radio-opacity using the unilateral ureteral
      obstruction model. Thus, virtual histology based on PTA contrast enhanced CT will
      in future help to refine the outcome of preclinical research on kidney associated
      murine disease models.

PMID- 29362428
TI  - Controlling AOX1 promoter strength in Pichia pastoris by manipulating poly
      (dA:dT) tracts.
AB  - Alcohol oxidase I (AOX1) promoter is the most popular but strictly-regulated
      methanol inducible promoter for heterologous protein expression in Pichia
      pastoris. In recent years, AOX1 promoter libraries have been developed with
      deletion or insertion methods. The present research manipulated poly (dA:dT)
      tracts in this promoter to control promoter strength, which hadn't been tried
      before. There were 34 variants derived from the native AOX1 promoter constructed.
      And variants were integrated into the same genomic location and upstream of the
      same reporter gene porcine growth hormone (pGH). To test the transferability of
      the results obtained from reporter gene pGH, the variants were connected to
      reporter gene Lac Z. The resulted promoter library spanned an activity range
      between 0.25 and 3.5 fold of the wild-type promoter activity. In addition,
      activities of variants correlated with their predicted nucleosome architecture,
      which were directed by poly (dA:dT) tracts. The cumulative sum of predicted
      nucleosome affinity across the region (-820 to -540) was related to promoters
      strength in single deletion variants on a proportional basis. Overall, the
      research promotes understanding of the regulatory patterns for AOX1 promoter and
      suggested that varying promoter expression of engineering nucleosome architecture
      was also a feasible approach in P. pastoris.

PMID- 29362429
TI  - Publisher Correction: Observation of photobleaching in Ge-deficient Ge16.8Se83.2
      chalcogenide thin film with prolonged irradiation.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29362430
TI  - Efficacy of bisphosphonates in the treatment of femoral head osteonecrosis: A
      PRISMA-compliant meta-analysis of animal studies and clinical trials.
AB  - This study aimed to determine whether bisphosphonates exert an effect on
      preventing femoral head collapse after osteonecrosis of the femoral head (ONFH)
      in an animal model and in clinical trials. A systematic literature search was
      performed for studies published up to January 2017. Twenty-three articles (16
      animal studies, seven clinical trials) were included in the meta-analysis. We
      found that the bisphosphonate group obtained significant improvement in
      epiphyseal quotients (MD = 15.32; 95% CI, 9.25-21.39) and provided better
      performance on bone volume (SMD = 1.57; 95% CI, 0.94-2.20), trabecular number
      (SMD = 1.30; 95% CI, 0.80-1.79), trabecular thickness (SMD = 0.77; 95% CI, 0.10
      1.43) and trabecular separation (SMD = -1.44; 95% CI, -1.70 to -0.58) in the
      animal model. However, the bisphosphonate group did not achieve better results in
      pain score, Harris score, the occurrence rate of femoral head collapse, or total
      hip arthroplasty in the clinical trials. In conclusion, despite bisphosphonates
      significantly improving bone remodeling outcomes in animal models, no significant
      efficacy was observed in the treatment of ONFH in the clinical studies. Further
      studies are required to solve the discordant outcomes between the animal and
      clinical studies.

PMID- 29362431
TI  - Dual roles of miR-374a by modulated c-Jun respectively targets CCND1-inducing
      PI3K/AKT signal and PTEN-suppressing Wnt/beta-catenin signaling in non-small-cell
      lung cancer.
AB  - MiR-374a appears to play a complex role in non-small-cell lung cancer (NSCLC).
      Here, we demonstrate a dual role for miR-374a in NSCLC pathogenesis. The effects
      and modulatory mechanisms of miR-374a on cell growth, migration, invasion, and in
      vivo tumorigenesis and metastasis in nude mice were also analyzed. The expression
      of miR-374a was examined in NSCLC and non-cancerous lung tissues by quantitative
      real-time reverse transcription-PCR (qRT-PCR), and in situ hybridization,
      respectively. miR-374a directly targets CCND1 and inactivates PI3K/AKT and Ras
      mediated cell cycle signalings, as well as epithelial-mesenchymal transition
      (EMT). This not only dramatically suppressed cell growth, migration, invasion,and
      metastasis, but also elevated A549 and pc-9 NSCLC cell sensitivity to cisplatin
      (DDP) while increasing survival time of tumor-bearing mice. Interestingly, miR
      374a serves an inverse function in SPCA-1 and H1975 NSCLC cells by directly
      targeting PTEN to activate Wnt/beta-catenin and Ras signalings and its downstream
      cascade signals. Surprisingly, transcription factor c-Jun bound to the promoter
      region of human miR-374a and suppressed miR-374a in A549 and pc-9 cells while
      inducing it in SPCA-1 and H1975 cells. Increased levels of miR-374a appeared to
      serve a protective role by targeting CCND1 in early-stage NSCLC (Stages I and
      II). Inversely, increased miR-374a was an unfavorable factor when targeting PTEN
      in more advanced staged NSCLC patients. Our studies are the first to demonstrate
      that miR-374a plays divergent roles in NSCLC pathogenesis at different stages of
      the disease and implicate the potential application of miR-374a targeting for
      cancer therapy.

PMID- 29362432
TI  - Nrf2 antioxidant pathway suppresses Numb-mediated epithelial-mesenchymal
      transition during pulmonary fibrosis.
AB  - Epithelial mesenchymal transition (EMT) is a key progression that promotes
      pulmonary fibrosis (PF). Numb, a phosphotyrosine-binding domain (PTB) protein, is
      implicated with EMT. Nuclear factor erythroid 2-related factor2 (Nrf2) and its
      downstream proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1
      (NQO1) constitute an important pathway of antioxidant defense signal for
      protecting against PF. It remains elusive whether Nrf2 antioxidant pathway and
      Numb have a potential relationship in EMT-mediated PF. Here, we observed the
      effects of Nrf2 pathway and Numb on bleomycin(BLM)-induced PF in Nrf2-knockout
      (Nrf2-/-) and wild-type (WT) mice. Meanwhile, rat type II alveolar epithelial
      cells line (RLE-6TN) and human epithelial cells line (A549) were both treated
      with an Nrf2 activator sulforaphane (SFN), or transfected siRNAs of Nrf2 and Numb
      to unravel roles of Nrf2 pathway, Numb and the link between them on transforming
      growth factor beta1 (TGF-beta1)-induced EMT. We found BLM-induced lung fibrosis
      were more severe in Nrf2-/- mice compared to WT mice with reduced expressions of
      HO-1 and NQO1. Numb was enhanced with down-regulated expressions of Nrf2 in BLM
      groups and further increased in Nrf2-/- groups. In vitro, given exogenous TGF
      beta1 on RLE-6TN and A549 up-regulated Numb expressions, accompanied with down
      regulations of Nrf2 and its target proteins HO-1 and NQO1. Transfected with Nrf2
      and Numb siRNAs further aggravated and relieved the progression of EMT,
      respectively. Inversely, activating Nrf2 pathway by SFN reduced the expression of
      Numb and EMT-related protein. Moreover, Numb deficiency by siRNA relieved the
      protection of activating Nrf2 against EMT. In conclusion, activating Nrf2
      antioxidant pathway suppresses EMT during PF via inhibiting the abnormal
      expression of Numb. These findings provide insight into PF pathogenesis and a
      basis for novel treatment approaches.

PMID- 29362433
TI  - Application of cardiovascular virtual endoscopy: a pilot study on roaming path
      planning for diagnosis of congenital heart diseases in children.
AB  - To investigate roaming paths planning for diagnosis of congenital heart diseases
      (CHD) using a cardiovascular virtual endoscopy (VE) system. Forty children were
      enrolled. VE system was applied to support in establishing a diagnosis.
      Performance in diagnosing CHDs by CT, VE using automatically planned roaming
      paths (VE-auto, objects were treated as left heart system and right heart
      system), VE using manually planned paths (VE-manual), and VE using automatically
      planned path for left heart system and manually planned path for right heart
      system (VE-combined) were studied and compared. Comparable accuracy of 93%, 93%,
      95% and 95% was found by CT, VE-auto, VE-manual and VE-combined. However, in
      diagnosing tetralogy of Fallot, significantly higher performance was found by
      VEs, compared with CT. For VE-auto, poor performance with an accuracy of 85% and
      sensitivity of 22% was revealed in diagnosing muscular ventricular septal defect,
      compared with VE-manual and VE-combined. Compared with VE-manual, VE-combined
      illustrated comparable diagnostic accuracy on all CHDs; however, significantly
      smaller diagnostic time was utilized (P < 0.05).Cardiovascular VE system
      demonstrated considerable clinical value in the diagnosis of CHDs. Left and right
      heart system should not be modeled as two cavity objects simultaneously. When one
      of two systems is treated as one object, the other system should be treated as
      three separate objects when using VE to diagnose CHDs.

PMID- 29362435
TI  - Chromium removal from aqueous solution by a PEI-silica nanocomposite.
AB  - It is essential and important to determine the adsorption mechanism as well as
      removal efficiency when using an adsorption technique to remove toxic heavy
      metals from wastewater. In this research, the removal efficiency and mechanism of
      chromium removal by a silica-based nanoparticle were investigated. A PEI-silica
      nanoparticle was synthesized by a one-pot technique and exhibited uniformly well
      dispersed PEI polymers in silica particles. The adsorption capacity of chromium
      ions was determined by a batch adsorption test, with the PEI-silica nanoparticle
      having a value of 183.7 mg/g and monolayer sorption. Adsorption of chromium ions
      was affected by the solution pH and altered the nanoparticle surface chemically.
      First principles calculations of the adsorption energies for the relevant
      adsorption configurations and XPS peaks of Cr and N showed that Cr(VI), [HCrO4]-
      is reduced to two species, Cr(III), CrOH2+ and Cr3+, by an amine group and that
      Cr(III) and Cr(VI) ions are adsorbed on different functional groups, oxidized N
      and NH3+.

PMID- 29362434
TI  - Effects of processing on structural, mechanical and biological properties of
      collagen-based substrates for regenerative medicine.
AB  - The aim of this work was to investigate the structural features of type I
      collagen isoforms and collagen-based films at atomic and molecular scales, in
      order to evaluate whether and to what extent different protocols of slurry
      synthesis may change the protein structure and the final properties of the
      developed scaffolds. Wide Angle X-ray Scattering data on raw materials
      demonstrated the preferential orientation of collagen molecules in equine tendon
      derived collagens, while randomly oriented molecules were found in bovine skin
      collagens, together with a lower crystalline degree, analyzed by the assessment
      of FWHM (Full Width at Half Maximum), and a certain degree of salt contamination.
      WAXS and FT-IR (Fourier Transform Infrared) analyses on bovine collagen-based
      films, showed that mechanical homogenization of slurry in acidic solution was the
      treatment ensuring a high content of super-organization of collagen into triple
      helices and a high crystalline domain into the material. In vitro tests on rat
      Schwannoma cells showed that Schwann cell differentiation into myelinating cells
      was dependent on the specific collagen film being used, and was found to be
      stimulated in case of homogenization-treated samples. Finally DHT/EDC
      crosslinking treatment was shown to affect mechanical stiffness of films
      depending on collagen source and processing conditions.

PMID- 29362436
TI  - Spectral mapping of brain functional connectivity from diffusion imaging.
AB  - Understanding the relationship between the dynamics of neural processes and the
      anatomical substrate of the brain is a central question in neuroscience. On the
      one hand, modern neuroimaging technologies, such as diffusion tensor imaging, can
      be used to construct structural graphs representing the architecture of white
      matter streamlines linking cortical and subcortical structures. On the other
      hand, temporal patterns of neural activity can be used to construct functional
      graphs representing temporal correlations between brain regions. Although some
      studies provide evidence that whole-brain functional connectivity is shaped by
      the underlying anatomy, the observed relationship between function and structure
      is weak, and the rules by which anatomy constrains brain dynamics remain elusive.
      In this article, we introduce a methodology to map the functional connectivity of
      a subject at rest from his or her structural graph. Using our methodology, we are
      able to systematically account for the role of structural walks in the formation
      of functional correlations. Furthermore, in our empirical evaluations, we observe
      that the eigenmodes of the mapped functional connectivity are associated with
      activity patterns associated with different cognitive systems.

PMID- 29362437
TI  - Seabird colonies as important global drivers in the nitrogen and phosphorus
      cycles.
AB  - Seabirds drastically transform the environmental conditions of the sites where
      they establish their breeding colonies via soil, sediment, and water
      eutrophication (hereafter termed ornitheutrophication). Here, we report worldwide
      amounts of total nitrogen (N) and total phosphorus (P) excreted by seabirds using
      an inventory of global seabird populations applied to a bioenergetics model. We
      estimate these fluxes to be 591 Gg N y-1 and 99 Gg P y-1, respectively, with the
      Antarctic and Southern coasts receiving the highest N and P inputs. We show that
      these inputs are of similar magnitude to others considered in global N and P
      cycles, with concentrations per unit of surface area in seabird colonies among
      the highest measured on the Earth's surface. Finally, an important fraction of
      the total excreted N (72.5 Gg y-1) and P (21.8 Gg y-1) can be readily
      solubilized, increasing their short-term bioavailability in continental and
      coastal waters located near the seabird colonies.

PMID- 29362438
TI  - Publisher Correction: Hydrogen storage and stability properties of Pd-Pt solid
      solution nanoparticles revealed via atomic and electronic structure.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29362439
TI  - Deletion of DGCR8 in VSMCs of adult mice results in loss of vascular reactivity,
      reduced blood pressure and neointima formation.
AB  - DiGeorge syndrome chromosomal region 8 (DGCR8), a double-stranded-RNA-binding
      protein, participates in the miRNA biogenesis pathway and contributes to miRNA
      maturation by interacting with the RNAase III enzyme Drosha in cell nuclei. To
      investigate the role of DGCR8 in vascular smooth muscle cells (VSMCs) at the
      postnatal stages, we generated tamoxifen-inducible VSMC specific knockout (iKO)
      mice by crossing DGCR8loxp/loxp with VSMC specific tamoxifen-inducible Cre
      transgenic mice SMA-Cre-ERT2. DGCR8iKO mice display reduced body weight one month
      following tamoxifen treatment and died around 3 months. Blood pressure and
      vascular reactivity were significantly reduced in DGCR8iKO mice compared to
      control. Furthermore, loss of DGCR8 in VSMCs inhibited cell proliferation,
      migration and neointima formation. VSMC differentiation marker genes, including
      SMA and SM22, were downregulated in DGCR8 iKO mice. The majority of miRNAs were
      downregulated in DGCR8iKO mice. Disruption of the DGCR8-mediated miRNA biogenesis
      pathway attenuated multiple signaling pathways including ERK1/2 and AKT. Our
      results demonstrate that the DGCR8-mediated miRNA pathway is required for
      maintaining blood pressure, vascular reactivity and vascular wall remodeling at
      the postnatal stages.

PMID- 29362441
TI  - Experimental identification of non-classicality of noisy twin beams and other
      related two-mode states.
AB  - Different non-classicality criteria expressed in the form of inequalities among
      intensity moments and elements of photon-number distributions are applied to
      noisy twin beams and other two-mode states obtained from a twin beam by using a
      beam splitter. Their performance in revealing the non-classicality is judged in
      comparison with the exact results provided by suitable entanglement and local non
      classicality quantifiers. Whereas the non-classicality of noisy twin beams is
      always revealed by these criteria, not all the nonclassical states obtained at
      the output of the beam splitter can be identified by these experimentally easily
      reachable criteria.

PMID- 29362440
TI  - The real-life costs of emotion regulation in anorexia nervosa: a combined
      ecological momentary assessment and fMRI study.
AB  - Regulation of emotions is necessary for successful attainment of short-term and
      long-term goals. However, over-regulation may also have its costs. In anorexia
      nervosa (AN), forgoing food intake despite emaciation and endocrine signals that
      promote eating is an example of "too much" self-control. Here we investigated
      whether voluntary emotion regulation in AN patients comes with associated
      disorder-relevant costs. Thirty-five patients with acute AN and thirty-five age
      matched healthy controls (HCs) performed an established emotion regulation
      paradigm during functional magnetic resonance imaging after an overnight fast.
      The task required reducing emotions induced by positively valenced pictures via
      distancing. We calculated a neural regulation score from responses recorded in a
      reward-related brain region of interest (ventral striatum; VS) by subtracting
      activation measured on "positive distance" trials from that elicited under the
      "positive watch" (baseline) condition. Complementing the imaging data, we used
      ecological momentary assessment (EMA) to probe disorder-related rumination and
      affect six times/day for 2 weeks following the scanning session. The neural
      regulation score indicating reduced VS activation during emotion regulation was
      used as a predictor in hierarchical linear models with EMA measures as outcomes.
      No group differences in neural activity were found for the main contrasts of the
      task. However, regulation of VS activity was associated with increased body
      related rumination and increased negative affect in AN, but not in HC. In line
      with this finding, correlational analysis with longitudinal BMI measurements
      revealed a link between greater VS regulation and poorer treatment outcome after
      60 and 90 days. Together, these results identify a neural correlate of altered
      emotion regulation in AN, which seems to be detrimental to psychological well
      being and may interfere with recovery.

PMID- 29362443
TI  - Ultrathin silicon oxynitride layer on GaN for dangling-bond-free GaN/insulator
      interface.
AB  - Despite the scientific and technological importance of removing interface
      dangling bonds, even an ideal model of a dangling-bond-free interface between GaN
      and an insulator has not been known. The formation of an atomically thin ordered
      buffer layer between crystalline GaN and amorphous SiO2 would be a key to
      synthesize a dangling-bond-free GaN/SiO2 interface. Here, we predict that a
      silicon oxynitride (Si4O5N3) layer can epitaxially grow on a GaN(0001) surface
      without creating dangling bonds at the interface. Our ab initio calculations show
      that the GaN/Si4O5N3 structure is more stable than silicon-oxide-terminated
      GaN(0001) surfaces. The electronic properties of the GaN/Si4O5N3 structure can be
      tuned by modifying the chemical components near the interface. We also propose a
      possible approach to experimentally synthesize the GaN/Si4O5N3 structure.

PMID- 29362442
TI  - New 5-Aryl-Substituted 2-Aminobenzamide-Type HDAC Inhibitors with a
      Diketopiperazine Group and Their Ameliorating Effects on Ischemia-Induced
      Neuronal Cell Death.
AB  - We previously synthesized new 5-thienyl-substituted 2-aminobenzamide-type HDAC1,
      2 inhibitors with the (4-ethyl-2,3-dioxopiperazine-1-carboxamido) methyl group. K
      560 (1a) protected against neuronal cell death in a Parkinson's disease model by
      up-regulating the expression of XIAP. This finding prompted us to design new K
      560-related compounds. We examined the structure activity relationship (SAR) for
      the neuronal protective effects of newly synthesized and known K-560 derivatives
      after cerebral ischemia. Among them, K-856 (8), containing the (4-methyl-2,5
      dioxopiperazin-1-yl) methyl group, exhibited a promising neuronal survival
      activity. The SAR study strongly suggested that the attachment of a monocyclic
      2,3- or 2,5-diketopiperazine group to the 2-amino-5-aryl (but not 2-nitro-5-aryl)
      scaffold is necessary for K-560-related compounds to exert a potent
      neuroprotective effect.

PMID- 29362444
TI  - Treatment of bipolar depression with minocycline and/or aspirin: an adaptive, 2*2
      double-blind, randomized, placebo-controlled, phase IIA clinical trial.
AB  - Given evidence of chronic inflammation in bipolar disorder (BD), we tested the
      efficacy of aspirin and minocycline as augmentation therapy for bipolar
      depression. Ninety-nine depressed outpatients with BD were enrolled in a 6 week,
      double-blind, placebo-controlled trial, and randomized to one of four groups:
      active minocycline (100 mg b.i.d.) + active aspirin (81 mg b.i.d.) (M + A);
      active minocycline + placebo aspirin (M + P); placebo-minocycline + active
      aspirin (A + P); and placebo-minocycline + placebo aspirin (P + P). A blinded
      interim analysis mid-way through the study led to the dropping of the M + P and A
      + P arms from further enrollment giving numbers per group who were included in
      the final analysis of: 30 (M + A), 18 (M + P), 19 (A + P), and 28 (P + P). When
      the study started, there were three primary outcome measures. Based on the
      results of the interim analysis, the primary outcome variable, response to
      treatment as defined by >50% decrease in Montgomery-Asberg Depression Rating
      Scale (MADRS) score was maintained. The other two (i.e., the change in mean MADRS
      score from baseline to end of study and the remission rate, with remission being
      defined as a score of <11 on the MADRS) were reduced to exploratory outcome
      measures because the interim analysis indicated that the study was adequately
      powered to test differences in response rate but not the mean change in MADRS
      scores or remission rates. CRP and IL-6 were assayed to measure inflammation.
      Urinary thromboxane B2 (11-D-TXB2) concentrations, which were significantly
      increased at baseline in the combined BD sample (n = 90) vs. a healthy control
      group (n = 27), served as an indirect marker of cyclooxygenase (COX) activity. In
      a two-group analysis, the M + A group showed a greater response rate than the P +
      P group (p(one-tailed) = 0.034, OR = 2.93, NNT = 4.7). When all four arms were
      included in the analysis, there was a main effect of aspirin on treatment
      response that was driven by both the M + A and the A + P groups (p(two-tailed) =
      0.019, OR = 3.67, NNT = 4.0). Additionally, there was a significant 3-way
      interaction between aspirin, minocycline, and IL-6, indicating that response to
      minocycline was significantly greater in participants in the M + P group with
      higher IL-6 concentrations. Further, participants in the M + P group who
      responded to treatment had significantly greater decreases in IL-6 levels between
      baseline and visit 7 vs. non-responders. Regarding the exploratory outcomes,
      there was a main effect for aspirin on the remission rate (chi12 = 4.14, p(2t) =
      0.04, OR = 2.52, NNT = 8.0). There was no significant main effect of aspirin or
      minocycline on the mean change in MADRS score across visits. Aspirin and
      minocycline may be efficacious adjunctive treatments for bipolar depression.
      Given their potential import, additional studies to confirm and extend these
      findings are warranted.

PMID- 29362445
TI  - Abnormal behaviours relevant to neurodevelopmental disorders in Kirrel3-knockout
      mice.
AB  - In the nervous system, Kirrel3 is involved in neuronal migration, axonal
      fasciculation, and synapse formation. Recently, genetic links have been reported
      between mutations in the KIRREL3 gene and increased risk of neurodevelopmental
      disorders, including autism spectrum disorder (ASD) and intellectual disability.
      To elucidate the causal relationship between KIRREL3 deficiency and behavioural
      abnormalities relevant to neurodevelopmental disorders, we generated global
      Kirrel3-knockout (Kirrel3-/-) mice and investigated the detailed behavioural
      phenotypes. In the three-chambered social approach test, Kirrel3-/- mice
      displayed a significant preference for a mouse over a non-social object but no
      significant preference for a stranger mouse over a familiar mouse. Ultrasonic
      communications, including pup-to-mother calls, male-female courtship vocalisation
      and resident responses to intruder, were significantly impaired in Kirrel3-/-
      mice. Significant increases in locomotor activity and repetitive rearing were
      also observed in Kirrel3-/- mice. Furthermore, the performance of Kirrel3-/- mice
      in the rotarod test was significantly better than that of wild-type mice. In the
      acoustic startle test, Kirrel3-/- mice were significantly hypersensitive to
      acoustic stimuli. Anxiety-related behaviours and spatial or fear memory
      acquisition were normal in Kirrel3-/- mice. These findings suggest that Kirrel3-/
      mice exhibit autistic-like behaviours, including social and communicative
      deficits, repetitive behaviours, and sensory abnormalities, as well as
      hyperactivity.

PMID- 29362446
TI  - Critical neutralizing fragment of Zika virus EDIII elicits cross-neutralization
      and protection against divergent Zika viruses.
AB  - Zika virus (ZIKV) infection remains a serious health threat due to its close
      association with congenital Zika syndrome (CZS), which includes microcephaly and
      other severe birth defects. As no vaccines are available for human use,
      continuous effort is needed to develop effective and safe vaccines to prevent
      ZIKV infection. In this study, we constructed three recombinant proteins
      comprising, respectively, residues 296-406 (E296-406), 298-409 (E298-409), and
      301-404 (E301-404) of ZIKV envelope (E) protein domain III (EDIII) fused with a C
      terminal Fc of human IgG. Our results demonstrated that E298-409 induced the
      highest titer of neutralizing antibodies against infection with nine ZIKV strains
      isolated from different hosts, countries, and time periods, and it maintained
      long-term anti-ZIKV immunogenicity to induce neutralizing antibodies. Pups born
      to mice immunized with E298-409 were fully protected against lethal challenge
      with two epidemic human ZIKV strains, 2015/Honduras (R103451) and 2015/Colombia
      (FLR). Passive transfer of anti-E298-409 mouse sera protected pups born to naive
      mice, as well as type I interferon receptor-deficient adult A129 mice, from
      lethal challenge with human ZIKV strains R103451 and FLR, and this protection was
      positively correlated with neutralizing antibodies. These data suggest that the
      critical neutralizing fragment (i.e., a fragment that can induce highly potent
      neutralizing antibodies against divergent ZIKV strains) of ZIKV EDIII is a good
      candidate for development as an effective and safe ZIKV subunit vaccine to
      protect pregnant mothers and their fetuses against ZIKV infection. The E298-409
      specific antibodies can be used for passive immunization to prevent ZIKV
      infection in newborns or immunocompromised adults.

PMID- 29362447
TI  - Mitochondria are transported along microtubules in membrane nanotubes to rescue
      distressed cardiomyocytes from apoptosis.
AB  - Membrane nanotubes (MNTs) act as "highways" between cells to facilitate the
      transfer of multiple signals and play an important role in many diseases. Our
      previous work reported on the transfer of mitochondria via MNTs between
      cardiomyocytes (CMs) and cardiac myofibroblasts (MFs); however, the elucidation
      of the underlying mechanism and pathophysiological significance of this transfer
      requires additional study. In this study, we determined that the mean movement
      velocity of mitochondria in MNTs between CMs and MFs was approximately 17.5 +/-
      2.1 nm/s. Meanwhile, treatment with microtubule polymerisation inhibitors
      nocodazole or colcemid in cell culture decreased mitochondrial velocity, and
      knockdown of the microtubule motor protein kinesin family member 5B (KIF5B) led
      to a similar effect, indicating that mitochondrial movement was dependent on
      microtubules and the motor protein KIF5B. Furthermore, we showed that
      hypoxia/reoxygenation-induced CM apoptosis was attenuated by coculture with
      intact or hypoxia/reoxygenation-treated MFs, which transferred mitochondria to
      CMs. This rescue was prevented either by separating the cells using Transwell
      culture or by impairing mitochondrial transfer with nocodazole or colcemid
      treatment. In conclusion, as a novel means of intercellular communication, MNTs
      rescue distressed CMs from apoptosis by transporting mitochondria along
      microtubules via KIF5B.

PMID- 29362448
TI  - Extracellular vesicle-mediated EBAG9 transfer from cancer cells to tumor
      microenvironment promotes immune escape and tumor progression.
AB  - The antitumor immune response is a critical defense system that eliminates
      malignant cells. The failure of the system results in immune escape and proceeds
      to tumor growth. We have previously showed that estrogen receptor-binding
      fragment-associated antigen 9 (EBAG9) is a relevant cancer biomarker and
      facilities immune escape of cancers from the immune surveillance. EBAG9 in cancer
      cells suppresses T-cell infiltration into tumor in vivo, whereas that in host
      immune cells functions as a limiter for T-cell cytotoxicity. Considering that
      EBAG9 plays immune suppressive roles in both tumor and microenvironment, we here
      questioned whether EBAG9 is a transferable protein from cancer to surrounding T
      cells and affects antitumor immune response. In this study, we showed that
      spontaneous development of prostate cancer was repressed in a model of Ebag9
      knockout mice crossed with transgenic adenocarcinoma of the mouse prostate
      (TRAMP) mice. We identified TM9SF1 as a collaborative EBAG9 interactor, which
      regulates epithelial-mesenchymal transition (EMT) in cancer cells. Notably,
      extracellular vesicles (EVs) from EBAG9-overexpressing prostate cancer cells have
      a potential to facilitate immune escape of tumors by inhibiting T-cell
      cytotoxicity and modulating immune-related gene expression in T cells.
      Furthermore, we showed that a neutralizing antibody for EBAG9 could rescue the EV
      mediated immune suppression by recovering T-cell cytotoxicity. In addition to its
      autocrine functions in cancer cells, EBAG9 could behave as a new class of immune
      checkpoint that suppresses tumor immunity in a secretory manner. We propose that
      EBAG9-targeting cancer treatment could be alternative therapeutic options for
      advanced diseases, particularly for those with EBAG9 overexpression.

PMID- 29362449
TI  - Heuristic and optimal policy computations in the human brain during sequential
      decision-making.
AB  - Optimal decisions across extended time horizons require value calculations over
      multiple probabilistic future states. Humans may circumvent such complex
      computations by resorting to easy-to-compute heuristics that approximate optimal
      solutions. To probe the potential interplay between heuristic and optimal
      computations, we develop a novel sequential decision-making task, framed as
      virtual foraging in which participants have to avoid virtual starvation. Rewards
      depend only on final outcomes over five-trial blocks, necessitating planning over
      five sequential decisions and probabilistic outcomes. Here, we report model
      comparisons demonstrating that participants primarily rely on the best available
      heuristic but also use the normatively optimal policy. FMRI signals in medial
      prefrontal cortex (MPFC) relate to heuristic and optimal policies and associated
      choice uncertainties. Crucially, reaction times and dorsal MPFC activity scale
      with discrepancies between heuristic and optimal policies. Thus, sequential
      decision-making in humans may emerge from integration between heuristic and
      optimal policies, implemented by controllers in MPFC.

PMID- 29362450
TI  - Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment
      in Mouse Peripheral Tissue.
AB  - Microbiota-derived short-chain fatty acids (SCFAs) and organic acids produced by
      the fermentation of non-digestible fibre can communicate from the microbiome to
      host tissues and modulate homeostasis in mammals. The microbiome has circadian
      rhythmicity and helps the host circadian clock function. We investigated the
      effect of SCFA or fibre-containing diets on circadian clock phase adjustment in
      mouse peripheral tissues (liver, kidney, and submandibular gland). Initially,
      caecal SCFA concentrations, particularly acetate and butyrate, induced
      significant day-night differences at high concentrations during the active
      period, which were correlated with lower caecal pH. By monitoring luciferase
      activity correlated with the clock gene Period2 in vivo, we found that oral
      administration of mixed SCFA (acetate, butyrate, and propionate) and an organic
      acid (lactate), or single administration of each SCFA or lactate for three days,
      caused phase changes in the peripheral clocks with stimulation timing dependency.
      However, this effect was not detected in cultured fibroblasts or cultured liver
      slices with SCFA applied to the culture medium, suggesting SCFA-induced indirect
      modulation of circadian clocks in vivo. Finally, cellobiose-containing diets
      facilitated SCFA production and refeeding-induced peripheral clock entrainment.
      SCFA oral gavage and prebiotic supplementation can facilitate peripheral clock
      adjustment, suggesting prebiotics as novel therapeutic candidates for
      misalignment.

PMID- 29362451
TI  - Sedimentological constraints on the initial uplift of the West Bogda Mountains in
      Mid-Permian.
AB  - The Late Paleozoic is considered to be an important stage in the evolution of the
      Central Asian Orogenic Belt (CAOB). The Bogda Mountains, a northeastern branch of
      the Tianshan Mountains, record the complete Paleozoic history of the Tianshan
      orogenic belt. The tectonic and sedimentary evolution of the west Bogda area and
      the timing of initial uplift of the West Bogda Mountains were investigated based
      on detailed sedimentological study of outcrops, including lithology, sedimentary
      structures, rock and isotopic compositions and paleocurrent directions. At the
      end of the Early Permian, the West Bogda Trough was closed and an island arc was
      formed. The sedimentary and subsidence center of the Middle Permian inherited
      that of the Early Permian. The west Bogda area became an inherited catchment
      area, and developed a widespread shallow, deep and then shallow lacustrine
      succession during the Mid-Permian. At the end of the Mid-Permian, strong
      intracontinental collision caused the initial uplift of the West Bogda Mountains.
      Sedimentological evidence further confirmed that the West Bogda Mountains was a
      rift basin in the Carboniferous-Early Permian, and subsequently entered the Late
      Paleozoic large-scale intracontinental orogeny in the region.

PMID- 29362452
TI  - Tell me about your hay fever: a qualitative investigation of allergic rhinitis
      management from the perspective of the patient.
AB  - Allergic rhinitis (AR) is sub-optimally managed in the community and is
      responsible for a significant health and economic burden. Uncontrolled AR
      increases the risk of poorly controlled asthma and presents an increased
      susceptibility to thunderstorm asthma. With the availability of treatments over
      the-counter, bypassing the health care professional (HCP), the role of the
      patient is paramount. Research on the role of the patient in AR management in the
      current environment is limited. This study aims to explore the patient
      perspective of AR management and understand why it is sub-optimally managed in
      the community. Patient perspectives of AR management were explored utilizing a
      qualitative, phenomenological approach. Adults with AR were included in the study
      and interviewed. Transcripts were analyzed for recurrent themes and emergent
      concepts. Forty-seven participants with AR were interviewed about their
      experiences. Patient reports of delayed diagnosis, treatment fatigue and
      confidence in the ability to manage their AR themselves, heavily influenced their
      management preferences. Patients also described barriers associated with AR
      management including financial expense as well as being mistaken for having an
      infectious disease. Patients described examples of the impact on their quality of
      life caused by their AR, yet they strongly believed they could manage it
      themselves. This belief that AR is a condition that should be entirely self
      managed, contributes to its burden. It amplifies patients' separation from HCPs
      and having access to guidelines aimed at optimizing their AR control.

PMID- 29362453
TI  - Insights into the molecular mechanism of dehalogenation catalyzed by D-2-haloacid
      dehalogenase from crystal structures.
AB  - D-2-haloacid dehalogenases (D-DEXs) catalyse the hydrolytic dehalogenation of D-2
      haloacids, releasing halide ions and producing the corresponding 2-hydroxyacids.
      A structure-guided elucidation of the catalytic mechanism of this dehalogenation
      reaction has not been reported yet. Here, we report the catalytic mechanism of a
      D-DEX, HadD AJ1 from Pseudomonas putida AJ1/23, which was elucidated by X-ray
      crystallographic analysis and the H218O incorporation experiment. HadD AJ1 is an
      alpha-helical hydrolase that forms a homotetramer with its monomer including two
      structurally axisymmetric repeats. The product-bound complex structure was
      trapped with L-lactic acid in the active site, which is framed by the
      structurally related helices between two repeats. Site-directed mutagenesis
      confirmed the importance of the residues lining the binding pocket in stabilizing
      the enzyme-substrate complex. Asp205 acts as a key catalytic residue and is
      responsible for activating a water molecule along with Asn131. Then, the hydroxyl
      group of the water molecule directly attacks the C2 atom of the substrate to
      release the halogen ion instead of forming an enzyme-substrate ester intermediate
      as observed in L-2-haloacid dehalogenases. The newly revealed structural and
      mechanistic information on D-DEX may inspire structure-based mutagenesis to
      engineer highly efficient haloacid dehalogenases.

PMID- 29362454
TI  - Nonalcoholic fatty liver disease is associated with dysbiosis independent of body
      mass index and insulin resistance.
AB  - This study aimed to determine if there is an association between dysbiosis and
      nonalcoholic fatty liver disease (NAFLD) independent of obesity and insulin
      resistance (IR). This is a prospective cross-sectional study assessing the
      intestinal microbiome (IM) of 39 adults with biopsy-proven NAFLD (15 simple
      steatosis [SS]; 24 nonalcoholic steatohepatitis [NASH]) and 28 healthy controls
      (HC). IM composition (llumina MiSeq Platform) in NAFLD patients compared to HC
      were identified by two statistical methods (Metastats, Wilcoxon). Selected taxa
      was validated using quantitative PCR (qPCR). Metabolites in feces and serum were
      also analyzed. In NAFLD, 8 operational taxonomic units, 6 genera, 6 families and
      2 phyla (Bacteroidetes, Firmicutes) were less abundant and; 1 genus
      (Lactobacillus) and 1 family (Lactobacillaceae) were more abundant compared to
      HC. Lower abundance in both NASH and SS patients compared to HC were confirmed by
      qPCR for Ruminococcus, Faecalibacterium prausnitzii and Coprococcus. No
      difference was found between NASH and SS. This lower abundance in NAFLD (NASH+SS)
      was independent of BMI and IR. NAFLD patients had higher concentrations of fecal
      propionate and isobutyric acid and serum 2-hydroxybutyrate and L-lactic acid.
      These findings suggest a potential role for a specific IM community and
      functional profile in the pathogenesis of NAFLD.

PMID- 29362456
TI  - Bone turnover, calcium homeostasis, and vitamin D status in Danish vegans.
AB  - BACKGROUND/OBJECTIVES: A vegan diet has been associated with increased bone
      fracture risk, but the physiology linking nutritional exposure to bone metabolism
      has only been partially elucidated. This study investigated whether a vegan diet
      is associated with increased bone turnover and altered calcium homeostasis due to
      insufficient intake of calcium and vitamin D. SUBJECTS/METHODS: Fractionated and
      total 25-hydroxyvitamin D (25(OH)-D), parathyroid hormone (PTH), calcium, and
      four bone turnover markers (osteocalcin, N-terminal propeptide of type I
      procollagen (PINP), bone-specific alkaline phosphatase (BAP), and C-terminal
      telopeptide of type I collagen (CTX)) were measured in serum from 78 vegans and
      77 omnivores. RESULTS: When adjusting for seasonality and constitutional
      covariates (age, sex, and body fat percentage) vegans had higher concentrations
      of PINP (32 [95% CI: 7, 64]%, P = 0.01) and BAP (58 [95% CI: 27, 97]%, P < 0.001)
      compared to omnivores, whereas CTX (30 [95% CI: -1, 72]%, P = 0.06) and
      osteocalcin (21.8 [95% CI: -9.3, 63.7]%, P = 0.2) concentrations did not differ
      between the two groups. Vegans had higher serum PTH concentration (38 [95% CI:
      19, 60]%; P < 0.001) and lower 25(OH)-D serum concentration (-33 [95% CI: -45, 
      19]%; P < 0.001), but similar serum calcium concentration (-1 [95% CI: -3, 1]%, P
      = 0.18 compared to omnivores. CONCLUSIONS: Vegans have higher levels of
      circulating bone turnover markers compared to omnivores, which may in the long
      term lead to poorer bone health. Differences in dietary habits including intake
      of vitamin D and calcium may, at least partly, explain the observed differences.

PMID- 29362457
TI  - Age modifies the association between serum obestatin, appetite and nutritional
      status in maintenance hemodialysis patients.
AB  - BACKGROUND/OBJECTIVES: Increased age is strongly associated with anorexia and
      protein-energy wasting (PEW) in maintenance hemodialysis (MHD) population. We
      hypothesized that the association of obestatin, a recently discovered
      anorexigenic gut hormone, with appetite and nutritional status differs by age
      groups. SUBJECTS/METHODS: We performed a cross-sectional study on 261MHD
      patients. Obestatin, acyl-ghrelin, markers of inflammation (CRP, IL-6, TNF-alpha)
      and nutrition (self-reported appetite, dietary intake, biochemical nutritional
      parameters, and body composition) were measured. RESULTS: Obestatin was
      associated with appetite in multivariate analyses even after controlling for such
      confounders as lean body mass (LBM), IL-6 and acyl-ghrelin in patients younger
      than 71 years. For each ng/ml increase in obestatin levels, the odds for
      diminished appetite was 0.75 (95% CI: 0.59-0.96). However, these associations
      were not observed in patients 71 years and older. Multivariable logistic
      regression models (including appetite) also showed increasing odds for PEW
      (defined by ESPEN consensus-based criteria for the diagnosis of malnutrition)
      across increasing serum obestatin levels (OR: 1.51, 95% CI: 1.05-2.18) in
      patients 71 years and older. However, after lean body mass (LBM) was added to
      this model, the association between obestatin and malnutrition was abolished (OR:
      1.26, 95% CI: 0.83-1.91). CONCLUSIONS: The association between serum obestatin,
      appetite and PEW differs depending on age in MHD patients. A positive link with
      appetite exists in patients younger than 71 years, whereas this relationship
      disappears by the age of 71. In older MHD patients, obestatin is associated with
      PEW through mechanisms related to LBM, but not to appetite.

PMID- 29362455
TI  - Dynamic recruitment of ubiquitin to mutant huntingtin inclusion bodies.
AB  - Many neurodegenerative diseases, such as Huntington's disease, are hallmarked by
      the formation of intracellular inclusion bodies (IBs) that are decorated with
      ubiquitin, proteasomes and chaperones. The apparent enrichment of ubiquitin and
      components involved in protein quality control at IBs suggests local ubiquitin
      dependent enzymatic activity. In this study, we examine recruitment of ubiquitin
      to IBs of polyglutamine-expanded huntingtin fragments (mHtt) by using synthesized
      TAMRA-labeled ubiquitin moieties. We show that intracellular TAMRA-ubiquitin is
      dynamic at mHtt IBs and is incorporated into poly-ubiquitin chains of
      intracellular substrates, such as mHtt, in a conjugation-dependent manner.
      Furthermore, we report that mHtt IBs recruit catalytically active enzymes
      involved in (de)-ubiquitination processes based on novel activity-based probes.
      However, we also find that the overexpression of the GFP-ubiquitin reporter,
      unlike the endogenous ubiquitin and TAMRA-ubiquitin, becomes irreversibly
      sequestered as a ring-like structure around the mHtt IBs, suggesting a methodical
      disadvantage of GFP-tagged ubiquitin. Our data provide supportive evidence for
      dynamic recruitment of ubiquitin and ubiquitin (de)-conjugating activity at mHtt
      initiated IBs.

PMID- 29362458
TI  - Body composition and development of diabetes: a 15-year follow-up study in a
      Japanese population.
AB  - BACKGROUND/OBJECTIVES: Few longitudinal studies have examined the association
      between diabetes risk and body composition in Asians. The aim of this prospective
      cohort study was to determine the role of body composition, estimated by whole
      body dual-energy X-ray absorptiometry, in the development of diabetes and to
      examine the impact of body composition on diabetes risk in normal weight (body
      mass index (BMI) <23 kg/m2) and overweight/obese groups (>=23 kg/m2).
      SUBJECTS/METHODS: We measured the body composition for 1532 diabetes-free
      subjects (463 men and 1069 women), aged 48-79 years, at the baseline examination
      period from 1994-96 and followed-up to detect new cases of diabetes over the next
      15 years (median 13.4 years). RESULTS: After being adjusted for BMI and other
      potential confounding factors, body fat distribution was associated with diabetes
      risk. Percentage of trunk fat was positively associated with the development of
      diabetes (hazards ratio (HR) per 1 SD (95% confidential interval (CI)), 1.58
      (1.10-2.28) in men, and 1.34 (0.99-1.83) in women), and percentage of leg fat was
      negatively associated with the development of diabetes (HR per 1 SD (95% CI),
      0.68 (0.50-0.91) in men and 0.68 (0.55-0.85) in women). The estimated HRs of %
      trunk and leg fat on the development of diabetes differed little between normal
      weight and overweight/obese subjects. Appendicular lean mass was also negatively
      associated with diabetes risk only in normal weight men. CONCLUSIONS: Opposite
      associations of trunk fat and leg fat with diabetes risk were observed.
      Assessment of body composition might help in the evaluation of diabetes risk.

PMID- 29362460
TI  - Pessimism and fearfulness in dairy calves.
AB  - Animals that experience situations likely to induce negative emotions show
      changes in judgment associated with pessimism. Few studies have focused on
      whether animals express stable differences in pessimism and whether these
      differences are related to personality traits. The first aim of this study was to
      explore if dairy calves are consistent over time in making judgments under
      ambiguous situations. Our second aim was to determine whether individual
      differences in judgment bias are related to conventional personality traits
      assessed using four standardized tests (Open field, Novel object, Human
      reactivity and Social motivation test). We subjected animals to two sessions of
      judgment bias and personality trait tests at 25 and 50 d of age. Individual
      differences in judgment bias were consistent over time with some animals
      persistently making more pessimistic choices compared to others. Two main
      dimensions of personality (Fearfulness and Sociability), obtained through
      principal component analysis, were also highly consistent over time. Pessimism
      was related to fearfulness, with more fearful calves making more pessimistic
      judgments. We conclude that dairy calves differ in the way they perceive and
      react to ambiguity and that this relates to individual differences in
      fearfulness.

PMID- 29362461
TI  - Asenjonamides A-C, antibacterial metabolites isolated from Streptomyces asenjonii
      strain KNN 42.f from an extreme-hyper arid Atacama Desert soil.
AB  - Bio-guided fractionation of the culture broth extract of Streptomyces asenjonii
      strain KNN 42.f recovered from an extreme hyper-arid Atacama Desert soil in
      northern Chile led to the isolation of three new bioactive beta-diketones;
      asenjonamides A-C (1-3) in addition to the known N-(2-(1H-indol-3-yl)-2
      oxoethyl)acetamide (4), a series of bioactive acylated 4-aminoheptosyl-beta-N
      glycosides; spicamycins A-E (5-9), and seven known diketopiperazines (10-16). All
      isolated compounds were characterized by HRESIMS and NMR analyses and tested for
      their antibacterial effect against a panel of bacteria.

PMID- 29362462
TI  - Acute inflammatory arthritis: Long-term effects of chikungunya.

PMID- 29362459
TI  - Lack of beta-arrestin signaling in the absence of active G proteins.
AB  - G protein-independent, arrestin-dependent signaling is a paradigm that broadens
      the signaling scope of G protein-coupled receptors (GPCRs) beyond G proteins for
      numerous biological processes. However, arrestin signaling in the collective
      absence of functional G proteins has never been demonstrated. Here we achieve a
      state of "zero functional G" at the cellular level using HEK293 cells depleted by
      CRISPR/Cas9 technology of the Gs/q/12 families of Galpha proteins, along with
      pertussis toxin-mediated inactivation of Gi/o. Together with HEK293 cells lacking
      beta-arrestins ("zero arrestin"), we systematically dissect G protein- from
      arrestin-driven signaling outcomes for a broad set of GPCRs. We use biochemical,
      biophysical, label-free whole-cell biosensing and ERK phosphorylation to identify
      four salient features for all receptors at "zero functional G": arrestin
      recruitment and internalization, but-unexpectedly-complete failure to activate
      ERK and whole-cell responses. These findings change our understanding of how
      GPCRs function and in particular of how they activate ERK1/2.

PMID- 29362464
TI  - Inflammation: Potassium channel regulates osteoclastogenesis.

PMID- 29362463
TI  - Systemic sclerosis: Promoting apoptosis is key to reversing fibrosis.

PMID- 29362465
TI  - Experimental arthritis: Anti-TNF kills the macrophage response.

PMID- 29362466
TI  - Behcet syndrome: a contemporary view.
AB  - This corrects the article DOI: 10.1038/nrrheum.2017.208.

PMID- 29362467
TI  - Moving towards a molecular taxonomy of autoimmune rheumatic diseases.
AB  - Autoimmune rheumatic diseases pose many problems that have, in general, already
      been solved in the field of cancer. The heterogeneity of each disease, the
      clinical similarities and differences between different autoimmune rheumatic
      diseases and the large number of patients that remain without a diagnosis
      underline the need to reclassify these diseases via new approaches. Knowledge
      about the molecular basis of systemic autoimmune diseases, along with the
      availability of bioinformatics tools capable of handling and integrating large
      volumes of various types of molecular data at once, offer the possibility of
      reclassifying these diseases. A new taxonomy could lead to the discovery of new
      biomarkers for patient stratification and prognosis. Most importantly, this
      taxonomy might enable important changes in clinical trial design to reach the
      expected outcomes or the design of molecularly targeted therapies. In this
      Review, we discuss the basis for a new molecular taxonomy for autoimmune
      rheumatic diseases. We highlight the evidence surrounding the idea that these
      diseases share molecular features related to their pathogenesis and development
      and discuss previous attempts to classify these diseases. We evaluate the tools
      available to analyse and combine different types of molecular data. Finally, we
      introduce PRECISESADS, a project aimed at reclassifying the systemic autoimmune
      diseases.

PMID- 29362470
TI  - Viral hepatitis: Biomarker for HBV therapy discontinuation.

PMID- 29362468
TI  - Corrigendum: The RA-MAP Consortium: a working model for academia-industry
      collaboration.
AB  - This corrects the article DOI: 10.1038/nrrheum.2017.200.

PMID- 29362469
TI  - Role of priority effects in the early-life assembly of the gut microbiota.
AB  - Understanding how microbial communities develop is essential for predicting and
      directing their future states. Ecological theory suggests that community
      development is often influenced by priority effects, in which the order and
      timing of species arrival determine how species affect one another. Priority
      effects can have long-lasting consequences, particularly if species arrival
      history varies during the early stage of community development, but their
      importance to the human gut microbiota and host health remains largely unknown.
      Here, we explore how priority effects might influence microbial communities in
      the gastrointestinal tract during early childhood and how the strength of
      priority effects can be estimated from the composition of the microbial species
      pool. We also discuss factors that alter microbial transmission, such as delivery
      mode, diet and parenting behaviours such as breastfeeding, which can influence
      the likelihood of priority effects. An improved knowledge of priority effects has
      the potential to inform microorganism-based therapies, such as prebiotics and
      probiotics, which are aimed at guiding the microbiota towards a healthy state.

PMID- 29362471
TI  - Discovery of novel bacterial topoisomerase I inhibitors by use of in silico
      docking and in vitro assays.
AB  - Topoisomerases are important targets for antibacterial and anticancer therapies.
      Bacterial topoisomerase I remains to be exploited for antibiotics that can be
      used in the clinic. Inhibitors of bacterial topoisomerase I may provide leads for
      novel antibacterial drugs against pathogens resistant to current antibiotics. TB
      is the leading infectious cause of death worldwide, and new TB drugs against an
      alternative target are urgently needed to overcome multi-drug resistance.
      Mycobacterium tuberculosis topoisomerase I (MtbTopI) has been validated
      genetically and chemically as a TB drug target. Here we conducted in silico
      screening targeting an active site pocket of MtbTopI. The top hits were assayed
      for inhibition of MtbTopI activity. The shared structural motif found in the
      active hits was utilized in a second round of in silico screening and in vitro
      assays, yielding selective inhibitors of MtbTopI with IC50s as low as 2 uM.
      Growth inhibition of Mycobacterium smegmatis by these compounds in combination
      with an efflux pump inhibitor was diminished by the overexpression of recombinant
      MtbTopI. This work demonstrates that in silico screening can be utilized to
      discover new bacterial topoisomerase I inhibitors, and identifies a novel
      structural motif which could be explored further for finding selective bacterial
      topoisomerase I inhibitors.

PMID- 29362472
TI  - Making spectral shape measurements in inverse Compton scattering a tool for
      advanced diagnostic applications.
AB  - Interaction of relativistic electron beams with high power lasers can both serve
      as a secondary light source and as a novel diagnostic tool for various beam
      parameters. For both applications, it is important to understand the dynamics of
      the inverse Compton scattering mechanism and the dependence of the scattered
      light's spectral properties on the interacting laser and electron beam
      parameters. Measurements are easily misinterpreted due to the complex interplay
      of the interaction parameters. Here we report the potential of inverse Compton
      scattering as an advanced diagnostic tool by investigating two of the most
      influential interaction parameters, namely the laser intensity and the electron
      beam emittance. Established scaling laws for the spectral bandwidth and redshift
      of the mean scattered photon energy are refined. This allows for a quantitatively
      well matching prediction of the spectral shape. Driving the interaction to a
      nonlinear regime, we spectrally resolve the rise of higher harmonic radiation
      with increasing laser intensity. Unprecedented agreement with 3D radiation
      simulations is found, showing the good control and characterization of the
      interaction. The findings advance the interpretation of inverse Compton
      scattering measurements into a diagnostic tool for electron beams from laser
      plasma acceleration.

PMID- 29362473
TI  - A single residue in the alphaB helix of the E protein is critical for Zika virus
      thermostability.

PMID- 29362474
TI  - Metabolomic analysis of low and high biofilm-forming Helicobacter pylori strains.
AB  - The biofilm-forming-capability of Helicobacter pylori has been suggested to be
      among factors influencing treatment outcome. However, H. pylori exhibit strain-to
      strain differences in biofilm-forming-capability. Metabolomics enables the
      inference of spatial and temporal changes of metabolic activities during biofilm
      formation. Our study seeks to examine the differences in metabolome of low and
      high biofilm-formers using the metabolomic approach. Eight H. pylori clinical
      strains with different biofilm-forming-capability were chosen for metabolomic
      analysis. Bacterial metabolites were extracted using Bligh and Dyer method and
      analyzed by Liquid Chromatography/Quadrupole Time-of-Flight mass spectrometry.
      The data was processed and analyzed using the MassHunter Qualitative Analysis and
      the Mass Profiler Professional programs. Based on global metabolomic profiles,
      low and high biofilm-formers presented as two distinctly different groups.
      Interestingly, low-biofilm-formers produced more metabolites than high-biofilm
      formers. Further analysis was performed to identify metabolites that differed
      significantly (p-value < 0.005) between low and high biofilm-formers. These
      metabolites include major categories of lipids and metabolites involve in
      prostaglandin and folate metabolism. Our findings suggest that biofilm formation
      in H. pylori is complex and probably driven by the bacterium' endogenous
      metabolism. Understanding the underlying metabolic differences between low and
      high biofilm-formers may enhance our current understanding of pathogenesis,
      extragastric survival and transmission of H. pylori infections.

PMID- 29362475
TI  - Lack of evidence for selection favouring MHC haplotypes that combine high
      functional diversity.
AB  - High rates of gene duplication and the highest levels of functional allelic
      diversity in vertebrate genomes are the main hallmarks of the major
      histocompatibility complex (MHC), a multigene family with a primordial role in
      pathogen recognition. The usual tight linkage among MHC gene duplicates may
      provide an opportunity for the evolution of haplotypes that associate
      functionally divergent alleles and thus grant the transmission of optimal levels
      of diversity to coming generations. Even though such associations may be a
      crucial component of disease resistance, this hypothesis has been given little
      attention in wild populations. Here, we leveraged pedigree data from a barn owl
      (Tyto alba) population to characterize MHC haplotype structure across two MHC
      class I (MHC-I) and two MHC class IIB (MHC-IIB) duplicates, in order to test the
      hypothesis that haplotypes' genetic diversity is higher than expected from
      randomly associated alleles. After showing that MHC loci are tightly linked
      within classes, we found limited evidence for shifts towards MHC haplotypes
      combining high diversity. Neither amino acid nor functional within-haplotype
      diversity were significantly higher than in random sets of haplotypes, regardless
      of MHC class. Our results therefore provide no evidence for selection towards
      high-diversity MHC haplotypes in barn owls. Rather, high rates of concerted
      evolution may constrain the evolution of high-diversity haplotypes at MHC-I,
      while, in contrast, for MHC-IIB, fixed differences among loci may provide barn
      owls with already optimized functional diversity. This suggests that at the MHC-I
      and MHC-IIB respectively, different evolutionary dynamics may govern the
      evolution of within-haplotype diversity.

PMID- 29362477
TI  - Random neuronal ensembles can inherently do context dependent coarse conjunctive
      encoding of input stimulus without any specific training.
AB  - Conjunctive encoding of inputs has been hypothesized to be a key feature in the
      computational capabilities of the brain. This has been inferred based on
      behavioral studies and electrophysiological recording from animals. In this
      report, we show that random neuronal ensembles grown on multi-electrode array
      perform a coarse-conjunctive encoding for a sequence of inputs with the first
      input setting the context. Such an encoding scheme creates similar yet unique
      population codes at the output of the ensemble, for related input sequences,
      which can then be decoded via a simple perceptron and hence a single STDP neuron
      layer. The random neuronal ensembles allow for pattern generalization and novel
      sequence classification without needing any specific learning or training of the
      ensemble. Such a representation of the inputs as population codes of neuronal
      ensemble outputs, has inherent redundancy and is suitable for further decoding
      via even probabilistic/random connections to subsequent neuronal layers. We
      reproduce this behavior in a mathematical model to show that a random neuronal
      network with a mix of excitatory and inhibitory neurons and sufficient
      connectivity creates similar coarse-conjunctive encoding of input sequences.

PMID- 29362476
TI  - Magneto-active substrates for local mechanical stimulation of living cells.
AB  - Cells are able to sense and react to their physical environment by translating a
      mechanical cue into an intracellular biochemical signal that triggers biological
      and mechanical responses. This process, called mechanotransduction, controls
      essential cellular functions such as proliferation and migration. The cellular
      response to an external mechanical stimulation has been investigated with various
      static and dynamic systems, so far limited to global deformations or to local
      stimulation through discrete substrates. To apply local and dynamic mechanical
      constraints at the single cell scale through a continuous surface, we have
      developed and modelled magneto-active substrates made of magnetic micro-pillars
      embedded in an elastomer. Constrained and unconstrained substrates are analysed
      to map surface stress resulting from the magnetic actuation of the micro-pillars
      and the adherent cells. These substrates have a rigidity in the range of cell
      matrices, and the magnetic micro-pillars generate local forces in the range of
      cellular forces, both in traction and compression. As an application, we followed
      the protrusive activity of cells subjected to dynamic stimulations. Our magneto
      active substrates thus represent a new tool to study mechanotransduction in
      single cells, and complement existing techniques by exerting a local and dynamic
      stimulation, traction and compression, through a continuous soft substrate.

PMID- 29362478
TI  - A specialized fungal parasite (Massospora cicadina) hijacks the sexual signals of
      periodical cicadas (Hemiptera: Cicadidae: Magicicada).
AB  - Male periodical cicadas (Magicicada spp.) infected with conidiospore-producing
      ("Stage I") infections of the entomopathogenic fungus Massospora cicadina exhibit
      precisely timed wing-flick signaling behavior normally seen only in sexually
      receptive female cicadas. Male wing-flicks attract copulation attempts from
      conspecific males in the chorus; close contact apparently spreads the infective
      conidiospores. In contrast, males with "Stage II" infections that produce resting
      spores that wait for the next cicada generation do not produce female-specific
      signals. We propose that these complex fungus-induced behavioral changes, which
      resemble apparently independently derived changes in other cicada-Massospora
      systems, represent a fungus "extended phenotype" that hijacks cicadas, turning
      them into vehicles for fungus transmission at the expense of the cicadas' own
      interests.

PMID- 29362480
TI  - Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth
      and confers non-small cell lung cancer patients with poor prognosis.
AB  - As a hallmark of cancer, the Warburg effect (aerobic glycolysis) confers a
      selective advantage for the survival and proliferation of cancer cells. Due to
      frequent aberration of upstream proto-oncogenes and tumor suppressors,
      hyperactive mammalian/mechanistic target of rapamycin (mTOR) is a potent inducer
      of the Warburg effect. Here, we report that overexpression of a glycolytic
      enzyme, phosphoglyceric acid mutase-1 (PGAM1), is critical to oncogenic mTOR
      mediated Warburg effect. mTOR stimulated PGAM1 expression through hypoxia
      inducible factor 1alpha-mediated transcriptional activation. Blockage of PGAM1
      suppressed mTOR-dependent glycolysis, cell proliferation, and tumorigenesis.
      PGAM1 expression and mTOR activity were positively correlated in non-small cell
      lung cancer (NSCLC) tissues and PGAM1 abundance was an adverse predictor for
      patient survival. PGAM1 is thus a downstream effector of mTOR signaling pathway
      and mTOR-PGAM1 signaling cascade may contribute to the development of Warburg
      effect observed in cancer. We consider PGAM1 as a novel prognostic biomarker for
      NSCLC and a therapeutic target for cancer.

PMID- 29362481
TI  - Enhancer of polycomb maintains germline activity and genome integrity in
      Drosophila testis.
AB  - Tissue homeostasis depends on the ability of tissue-specific adult stem cells to
      maintain a balance between proliferation and differentiation, as well as ensure
      DNA damage repair. Here, we use the Drosophila male germline stem cell system to
      study how a chromatin factor, enhancer of polycomb [E(Pc)], regulates the
      proliferation-to-differentiation (mitosis-to-meiosis) transition and DNA damage
      repair. We identified two critical targets of E(Pc). First, E(Pc) represses CycB
      transcription, likely through modulating H4 acetylation. Second, E(Pc) is
      required for accumulation of an important germline differentiation factor, Bag-of
      marbles (Bam), through post-transcriptional regulation. When E(Pc) is
      downregulated, increased CycB and decreased Bam are both responsible for
      defective mitosis-to-meiosis transition in the germline. Moreover, DNA double
      strand breaks (DSBs) accumulate upon germline inactivation of E(Pc) under both
      physiological condition and recovery from heat shock-induced endonuclease
      expression. Failure of robust DSB repair likely leads to germ cell loss. Finally,
      compromising the activity of Tip60, a histone acetyltransferase, leads to
      germline defects similar to E(Pc) loss-of-function, suggesting that E(Pc) acts
      cooperatively with Tip60. Together, our data demonstrate that E(Pc) has
      pleiotropic roles in maintaining male germline activity and genome integrity. Our
      findings will help elucidate the in vivo molecular mechanisms of E(Pc).

PMID- 29362482
TI  - Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR
      regulated autophagy.
AB  - Despite the high efficacy and safety of arsenic trioxide (ATO) in treating acute
      promyelocytic leukemia (APL) and eradicating APL leukemia-initiating cells
      (LICs), the mechanism underlying its selective cytotoxicity remains elusive. We
      have recently demonstrated that APL cells undergo a novel cell death program,
      termed ETosis, through autophagy. However, the role of ETosis in ATO-induced APL
      LIC eradication remains unclear. For this study, we evaluated the effects of ATO
      on ETosis and the contributions of drug-induced ETosis to APL LIC eradication. In
      NB4 cells, ATO primarily increased ETosis at moderate concentrations (0.5-0.75
      MUM) and stimulated apoptosis at higher doses (1.0-2.0 MUM). Furthermore, ATO
      induced ETosis through mammalian target of rapamycin (mTOR)-dependent autophagy,
      which was partially regulated by reactive oxygen species. Additionally, rapamycin
      enhanced ATO-induced ETosis in NB4 cells and APL cells from newly diagnosed and
      relapsed patients. In contrast, rapamycin had no effect on apoptosis in these
      cells. We also noted that PML/RARA oncoprotein was effectively cleared with this
      combination. Intriguingly, activation of autophagy with rapamycin-enhanced APL
      LIC eradication clearance by ATO in vitro and in a xenograft APL model, while
      inhibition of autophagy spared clonogenic cells. Our current results show that
      ATO exerts antileukemic effects at least partially through ETosis and targets
      LICs primarily through ETosis. Addition of drugs that target the ETotic pathway
      could be a promising therapeutic strategy to further eradicate LICs and reduce
      relapse.

PMID- 29362483
TI  - Inhibition of p53 prevents diabetic cardiomyopathy by preventing early-stage
      apoptosis and cell senescence, reduced glycolysis, and impaired angiogenesis.
AB  - Elevated tumor suppressor p53 expression has been associated with heart diseases,
      including the diabetic heart. However, its precise role in the pathogenesis of
      diabetic cardiomyopathy (DCM) remains unclear. We hypothesized that the
      development of DCM is attributed to up-regulated p53-mediated both early cardiac
      cell death and persistent cell senescence, glycolytic and angiogenetic
      dysfunctions. The present study investigated the effect of p53 inhibition with
      its specific inhibitor pifithrin-alpha (PFT-alpha) on the pathogenesis of DCM and
      its associated mechanisms. Type 1 diabetes was induced with multiple low doses of
      streptozotocin. Both hyperglycemic and age-matched control mice were treated with
      and without PFT-alpha five times a week for 2 months and then sacrificed at 3 and
      6 months post-diabetes. Treatment with PFT-alpha significantly prevented the
      progression of diabetes-induced cardiac remodeling and dysfunction (i.e., DCM).
      Mechanistically, the inhibition of p53 prevented the cardiac apoptosis during
      early-stage diabetes (0.5 month), attenuated diabetes-induced cell senescence (3
      and 6 months), and improved both glycolytic and angiogenic defects by increasing
      hypoxia-induced factor (HIF)-1alpha protein stability and upregulating HIF-1alpha
      transcription of specific target genes at 3 and 6 months after diabetes.
      Therefore, the targeted inhibition of p53 in diabetic individuals may provide a
      novel approach for the prevention of DCM.

PMID- 29362484
TI  - Whole Organ Blood and Lymphatic Vessels Imaging (WOBLI).
AB  - Thin section histology is limited in providing 3D structural information,
      particularly of the intricate morphology of the vasculature. Availability of high
      spatial resolution imaging for thick samples, would overcome the restriction
      dictated by low light penetration. Our study aimed at optimizing the procedure
      for efficient and affordable tissue clearing, along with an appropriate
      immunofluorescence labeling that will be applicable for high resolution imaging
      of blood and lymphatic vessels. The new procedure, termed whole organ blood and
      lymphatic vessels imaging (WOBLI), is based on two previously reported methods,
      CLARITY and ScaleA2. We used this procedure for the analysis of isolated whole
      ovary, uterus, lung and liver. These organs were subjected to passive clearing,
      following fixation, immunolabeling and embedding in hydrogel. Cleared specimens
      were immersed in ScaleA2 solution until transparency was achieved and imaged
      using light sheet microscopy. We demonstrate that WOBLI allows detailed analysis
      and generation of structural information of the lymphatic and blood vasculature
      from thick slices and more importantly, from whole organs. We conclude that WOBLI
      offers the advantages of morphology and fluorescence preservation with efficient
      clearing. Furthermore, WOBLI provides a robust, cost-effective method for
      generation of transparent specimens, allowing high resolution, 3D-imaging of
      blood and lymphatic vessels networks.

PMID- 29362485
TI  - Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson
      disease. alpha-Lipoic acid as a potential anti-copper agent.
AB  - Wilson disease is an autosomal recessive genetic disorder caused by loss-of
      function mutations in the P-type copper ATPase, ATP7B, which leads to toxic
      accumulation of copper mainly in the liver and brain. Wilson disease is
      treatable, primarily by copper-chelation therapy, which promotes copper
      excretion. Although several de-coppering drugs are currently available, their
      Cu(I)-binding affinities have not been quantitatively characterized. Here we
      determined the Cu(I)-binding affinities of five major de-coppering drugs - D
      penicillamine, trientine, 2,3-dimercapto-1-propanol, meso-2,3-dimercaptosuccinate
      and tetrathiomolybdate - by exploring their ability to extract Cu(I) ions from
      two Cu(I)-binding proteins, the copper chaperone for cytochrome c oxidase, Cox17,
      and metallothionein. We report that the Cu(I)-binding affinity of these drugs
      varies by four orders of magnitude and correlates positively with the number of
      sulfur atoms in the drug molecule and negatively with the number of atoms
      separating two SH groups. Based on the analysis of structure-activity
      relationship and determined Cu(I)-binding affinity, we hypothesize that the
      endogenous biologically active substance, alpha-lipoic acid, may be suitable for
      the treatment of Wilson disease. Our hypothesis is supported by cell culture
      experiments where alpha-lipoic acid protected hepatic cells from copper toxicity.
      These results provide a basis for elaboration of new generation drugs that may
      provide better therapeutic outcomes.

PMID- 29362486
TI  - Virtual craniotomy for high-resolution optoacoustic brain microscopy.
AB  - Ultrasound-mediated transcranial images of the brain often suffer from acoustic
      distortions produced by the skull bone. In high-resolution optoacoustic
      microscopy, the skull-induced acoustic aberrations are known to impair image
      resolution and contrast, further skewing the location and intensity of the
      different absorbing structures. We present a virtual craniotomy deconvolution
      algorithm based on an ultrasound wave propagation model that corrects for the
      skull-induced distortions in optically-resolved optoacoustic transcranial
      microscopy data. The method takes advantage of the geometrical and spectral
      information of a pulse-echo ultrasound image of the skull simultaneously acquired
      by our multimodal imaging system. Transcranial mouse brain imaging experiments
      confirmed the ability to accurately account for the signal amplitude decay,
      temporal delay and pulse broadening introduced by the rodent's skull. Our study
      is the first to demonstrate skull-corrected transcranial optoacoustic imaging in
      vivo.

PMID- 29362487
TI  - The Transmission and Evolution of HIV-1 Quasispecies within One Couple: a Follow
      up Study based on Next-Generation Sequencing.
AB  - Next-generation sequencing (NGS) has been successfully used to trace HIV-1
      infection. In this study, we investigated the transmission and evolution of HIV-1
      quasispecies in a couple infected through heterosexual behavior. A heterosexual
      couple in which both partners were infected with HIV-1 was followed up for 54
      months. Blood samples including whole-blood and plasma samples, were collected at
      various time points. After HIV-1 subtyping, NGS (Miseq platform) was used to
      sequence the env region of the HIV-1 quasispecies. Genetic distances were
      calculated, and phylogenetic trees were generated. We found both partners were
      infected with HIV-1 subtype circulating recombinant form (CRF), CRF65_cpx. The
      quasispecies distribution was relatively tightly clustered in the phylogenetic
      tree during early infection. Over time, the distribution of HIV-1 quasispecies
      gradually became more dispersed at 12th months, with a progressive increase in
      gene diversity. By 37th months, the sequences obtained for both partners formed
      different clusters in the phylogenetic tree. These results suggest that the HIV-1
      contact tracing results generated by the Miseq platform may be more reliable than
      other conventional sequencing methods, which can provide important information
      about the transmission and evolution of HIV-1. Our findings may help to better
      target preventative interventions for promoting public health.

PMID- 29362488
TI  - Transcriptional regulation of P63 on the apoptosis of male germ cells and three
      stages of spermatogenesis in mice.
AB  - Infertility affects 10-15% of couples worldwide, and male factors account for
      50%. Spermatogenesis is precisely regulated by genetic factors, and the mutations
      of genes result in abnormal spermatogenesis and eventual male infertility. The
      aim of this study was to explore the role and transcriptional regulation of P63
      in the apoptosis and mouse spermatogenesis. P63 protein was decreased in male
      germ cells of P63(+/-) mice compared with wild-type mice. There was no obvious
      difference in testis weight, sperm motility, and fecundity between P63(+/-) and
      wild-type mice. However, abnormal germ cells were frequently observed in P63(+/-)
      mice at 2 months old. Notably, apoptotic male germ cells and the percentage of
      abnormal sperm were significantly enhanced in P63(+/-) mice compared to wild-type
      mice. Spermatogonia, pachytene spermatocytes and round spermatids were isolated
      from P63(+/-) and wild-type mice using STA-PUT velocity sedimentation, and they
      were identified phenotypically with high purities. RNA sequencing demonstrated
      distinct transcription profiles in spermatogonia, pachytene spermatocytes, and
      round spermatids between P63(+/-) mice and wild-type mice. In total, there were
      645 differentially expressed genes (DEGs) in spermatogonia, 106 DEGs in pachytene
      spermatocytes, and 1152 in round spermatids between P63(+/-) mice and wild-type
      mice. Real time PCR verified a number of DEGs identified by RNA sequencing. Gene
      ontology annotation and pathway analyzes further indicated that certain key
      genes, e.g., Ccnd2, Tgfa, Hes5, Insl3, Kit, Lef1, and Jun were involved in
      apoptosis, while Dazl, Kit, Pld6, Cdkn2d, Stra8, and Ubr2 were associated with
      regulating spermatogenesis. Collectively, these results implicate that P63
      mediates the apoptosis of male germ cells and regulates three stages of
      spermatogenesis transcriptionally. This study could provide novel targets for the
      diagnosis and treatment of male infertility.

PMID- 29362490
TI  - Publisher Correction: Functional coupling of human pancreatic islets and liver
      spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29362489
TI  - Genetic variant in CACNA1C is associated with PTSD in traumatized police
      officers.
AB  - Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that
      may develop after a traumatic event. Here we aimed to identify epigenetic and
      genetic loci associated with PTSD. We included 73 traumatized police officers
      with extreme phenotypes regarding symptom severity despite similar trauma
      history: n = 34 had PTSD and n = 39 had minimal PTSD symptoms. Epigenetic and
      genetic profiles were based on the Illumina HumanMethylation450 BeadChip. We
      searched for differentially methylated probes (DMPs) and differentially
      methylated regions (DMRs). For genetic associations we analyzed the CpG-SNPs
      present on the array. We detected no genome-wide significant DMPs and we did not
      replicate previously reported DMPs associated with PTSD. However, GSE analysis of
      the top 100 DMPs showed enrichment of three genes involved in the dopaminergic
      neurogenesis pathway. Furthermore, we observed a suggestive association of one
      relatively large DMR between patients and controls, which was located at the PAX8
      gene and previously associated with other psychiatric disorders. Finally, we
      validated five PTSD-associated CpG-SNPs identified with the array using sanger
      sequencing. We subsequently replicated the association of one common SNP
      (rs1990322) in the CACNA1C locus with PTSD in an independent cohort of
      traumatized children. The CACNA1C locus was previously associated with other
      psychiatric disorders, but not yet with PTSD. Thus, despite the small sample
      size, inclusion of extreme symptom severity phenotypes in a highly homogenous
      traumatized cohort enabled detection of epigenetic and genetic loci associated
      with PTSD. Moreover, here we showed that genetically confounded 450K probes are
      informative for genetic association analysis.

PMID- 29362491
TI  - On the thermodynamic origin of metabolic scaling.
AB  - The origin and shape of metabolic scaling has been controversial since Kleiber
      found that basal metabolic rate of animals seemed to vary as a power law of their
      body mass with exponent 3/4, instead of 2/3, as a surface-to-volume argument
      predicts. The universality of exponent 3/4 -claimed in terms of the fractal
      properties of the nutrient network- has recently been challenged according to
      empirical evidence that observed a wealth of robust exponents deviating from 3/4.
      Here we present a conceptually simple thermodynamic framework, where the
      dependence of metabolic rate with body mass emerges from a trade-off between the
      energy dissipated as heat and the energy efficiently used by the organism to
      maintain its metabolism. This balance tunes the shape of an additive model from
      which different effective scalings can be recovered as particular cases, thereby
      reconciling previously inconsistent empirical evidence in mammals, birds, insects
      and even plants under a unified framework. This model is biologically motivated,
      fits remarkably well the data, and also explains additional features such as the
      relation between energy lost as heat and mass, the role and influence of
      different climatic environments or the difference found between endotherms and
      ectotherms.

PMID- 29362492
TI  - Novel compound heterozygous DPH1 mutations in a patient with the unique clinical
      features of airway obstruction and external genital abnormalities.
AB  - The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential
      components of the enzyme catalyzing the first step of diphthamide formation on
      eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally
      modified histidine residue on EEF2 that promotes protein chain elongation in the
      ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2,
      leading to growth defects, embryonic lethality, and cell death. In humans, DPH1
      mutations cause developmental delay with a short stature, dysmorphic features,
      and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901).
      To date, only two homozygous missense mutations in DPH1 (c.17T>A, p.Met6Lys and
      c.701T>C, p.Leu234Pro) have been reported. We used WES to identify novel compound
      heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C,
      p.Leu164Pro) in a patient from a nonconsanguineous family presenting with
      intellectual disability, a short stature, craniofacial abnormalities, and
      external genital abnormalities. The clinical phenotype of all patients with DPH1
      mutations, including the current patient, revealed core features, although the
      external genital anomaly was newly recognized in our case.

PMID- 29362493
TI  - Identification of IFRD1 variant in a Han Chinese family with autosomal dominant
      hereditary spastic paraplegia associated with peripheral neuropathy and ataxia.
AB  - Spinocerebellar ataxias (SCAs) are a group of autosomal dominant, clinically
      heterogeneous neurodegenerative disorders. SCA18 is a rare autosomal dominant
      sensory/motor neuropathy with ataxia (OMIM#607458) associated with a single
      missense variant c.514 A>G in the interferon related developmental regulator 1
      (IFRD1) gene previously reported in a five-generation American family of Irish
      origin. However, to date, there have been no other reports of the IFRD1 mutation
      to confirm its role in SCA. Here, we report a Han Chinese family with SCA18; the
      family members presented with a slowly progressing gait ataxia, pyramidal tract
      signs, and peripheral neuropathy. We identified a missense variant (c.514 A>G,
      p.I172V) in IFRD1 gene in the family using targeted next-generation sequencing
      and Sanger direct sequencing with specific primers. Our results suggest that the
      IFRD1 gene may be the causative allele for SCA18.

PMID- 29362495
TI  - Publisher Correction: Utf1 contributes to intergenerational epigenetic
      inheritance of pluripotency.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29362494
TI  - Seizure development in the acute intrahippocampal epileptic focus.
AB  - Currently, an epileptic seizure is considered to involve a temporary network that
      exists for a finite period of time. Formation of this network evolves through
      spread of epileptiform activity from a seizure onset zone (SOZ). Propagation of
      seizures evoked by kainic acid injection in hippocampus to different brain areas
      was analyzed at macro- and micro-intervals. The mean latency of seizure
      occurrence in different brain areas varied between 0.5 sec and 85 sec (mean 14.9
      +/- 14.5 (SD)), and it increased after each consecutive seizure in areas located
      contralateral to the area of injection, but not in the ipsilateral sites. We have
      shown that only 41% of epileptic individual events in target brain areas were
      driven by epileptic events generated in the SOZ once the seizure began. Fifty
      nine percent of epileptiform events in target areas occurred one millisecond
      before or after events in the SOZ. These data illustrate that during seizure
      maintenance, only some individual epileptiform events in areas outside of SOZ
      could be consistently triggered by the SOZ; and the majority must be triggered by
      a driver located outside the SOZ or brain areas involved in ictal activity could
      be coupled to each other via an unknown mechanism such as stochastic resonance.

PMID- 29362496
TI  - The microRNA regulatory landscape of MSC-derived exosomes: a systems view.
AB  - Mesenchymal stem cell (MSC)-derived exosomes mediate tissue regeneration in a
      variety of diseases including ischemic heart injury, liver fibrosis, and
      cerebrovascular disease. Despite an increasing number of studies reporting the
      therapeutic effects of MSC exosomes, the underlying molecular mechanisms and
      their miRNA complement are poorly characterized. Here we microRNA (miRNA)
      profiled MSC exosomes and conducted a network analysis to identify the dominant
      biological processes and pathways modulated by exosomal miRNAs. At a system
      level, miRNA-targeted genes were enriched for (cardio)vascular and angiogenesis
      processes in line with observed cardiovascular regenerative effects. Targeted
      pathways were related to Wnt signaling, pro-fibrotic signaling via TGF-beta and
      PDGF, proliferation, and apoptosis. When tested, MSC exosomes reduced collagen
      production by cardiac fibroblasts, protected cardiomyocytes from apoptosis, and
      increased angiogenesis in HUVECs. The intrinsic beneficial effects were further
      improved by virus-free enrichment of MSC exosomes with network-informed
      regenerative miRNAs capable of promoting angiogenesis and cardiomyocyte
      proliferation. The data presented here help define the miRNA landscape of MSC
      exosomes, establish their biological functions through network analyses at a
      system level, and provide a platform for modulating the overall phenotypic
      effects of exosomes.

PMID- 29362498
TI  - Nonsymmorphic symmetry protected node-line semimetal in the trigonal YH3.
AB  - Using ab initio calculations based on density-functional theory and effective
      model analysis, we propose that the trigonal YH3 (Space Group: P[Formula: see
      text]c1) at ambient pressure is a node-line semimetal when spin-orbit coupling
      (SOC) is ignored. This trigonal YH3 has very clean electronic structure near
      Fermi level and its nodal lines locate very closely to the Fermi energy, which
      makes it a perfect system for model analysis. Symmetry analysis shows that the
      nodal ring in this compound is protected by the glide-plane symmetry, where the
      band inversion of |Y+, d xz > and |H1-, s> orbits at Gamma point is responsible
      for the formation of the nodal lines. When SOC is included, the line nodes are
      prohibited by the glide-plane symmetry, and a small gap (~5 meV) appears, which
      leads YH3 to be a strong topological insulator with Z2 indices (1,000). Thus the
      glide-plane symmetry plays an opposite role in the formation of the nodal lines
      in cases without and with SOC. As the SOC-induced gap is so small that can be
      neglected, this P[Formula: see text]c1 YH3 may be a good candidate for
      experimental explorations on the fundamental physics of topological node-line
      semimetals. We find the surface states of this P[Formula: see text]c1 phase are
      somehow unique and may be helpful to identify the real ground state of YH3 in the
      experiment.

PMID- 29362499
TI  - First experimental observations on melting and chemical modification of volcanic
      ash during lightning interaction.
AB  - Electrification in volcanic ash plumes often leads to syn-eruptive lightning
      discharges. High temperatures in and around lightning plasma channels have the
      potential to chemically alter, re-melt, and possibly volatilize ash fragments in
      the eruption cloud. In this study, we experimentally simulate temperature
      conditions of volcanic lightning in the laboratory, and systematically
      investigate the effects of rapid melting on the morphology and chemical
      composition of ash. Samples of different size and composition are ejected towards
      an artificially generated electrical arc. Post-experiment ash morphologies
      include fully melted spheres, partially melted particles, agglomerates, and
      vesiculated particles. High-speed imaging reveals various processes occurring
      during the short lightning-ash interactions, such as particle melting and
      rounding, foaming, and explosive particle fragmentation. Chemical analyses of the
      flash-melted particles reveal considerable bulk loss of Cl, S, P and Na through
      thermal vaporization. Element distribution patterns suggest convection as a key
      process of element transport from the interior of the melt droplet to rim where
      volatiles are lost. Modeling the degree of sodium loss delivers maximum melt
      temperatures between 3290 and 3490 K. Our results imply that natural lighting
      strikes may be an important agent of syn-eruptive morphological and chemical
      processing of volcanic ash.

PMID- 29362497
TI  - ATP-mediated Events in Peritubular Cells Contribute to Sterile Testicular
      Inflammation.
AB  - Peritubular myoid cells, which form the walls of seminiferous tubules in the
      testis, are functionally unexplored. While they transport sperm and contribute to
      the spermatogonial stem cell niche, specifically their emerging role in the
      immune surveillance of the testis and in male infertility remains to be studied.
      Recently, cytokine production and activation of Toll-like receptors (TLRs) were
      uncovered in cultured peritubular cells. We now show that human peritubular cells
      express purinergic receptors P2RX4 and P2RX7, which are functionally linked to
      TLRs, with P2RX4 being the prevalent ATP-gated ion channel. Subsequent ATP
      treatment of cultured peritubular cells resulted in up-regulated (pro
      )inflammatory cytokine expression and secretion, while characteristic peritubular
      proteins, that is smooth muscle cell markers and extracellular matrix molecules,
      decreased. These findings indicate that extracellular ATP may act as danger
      molecule on peritubular cells, able to promote inflammatory responses in the
      testicular environment.

PMID- 29362500
TI  - On terahertz pulsed broadband Gauss-Bessel beam free-space propagation.
AB  - Terahertz pulse time-domain holography is the ultimate technique allowing the
      evaluating a propagation of pulse broadband terahertz wavefronts and analyze
      their spatial, temporal and spectral evolution. We have numerically analyzed
      pulsed broadband terahertz Gauss-Bessel beam's both spatio-temporal and spatio
      spectral evolution in the non-paraxial approach. We have characterized two
      dimensional spatio-temporal beam behavior and demonstrated all stages of pulse
      reshaping during the propagation, including X-shape pulse forming. The reshaping
      is also illustrated by the energy transfer dynamics, where the pulse energy flows
      from leading edge to trailing edge. This behavior illustrates strong spatio
      temporal coupling effect when spatio-temporal distribution of Bessel beam's
      wavefront depends on propagation distance. The spatio-temporal and spatio
      spectral profiles for different spectral components clearly illustrate the model
      where the Bessel beam's wavefront at the exit from the axicon can be divided into
      radial segments for which the wave vectors intersect. Phase velocity via
      propagation distance is estimated and compared with existing experimantal
      results. Results of the phase velocity calculation depend strongly on distance
      increment value, thus demonstrating superluminal or subluminal behavior.

PMID- 29362501
TI  - Sequential transfection of RUNX2/SP7 and ATF4 coated onto dexamethasone-loaded
      nanospheresenhances osteogenesis.
AB  - The timing of gene transfection greatly influences stem cell differentiation.
      Sequential transfection is crucial for regulation of cell behavior. When
      transfected several days after differentiation initiation, genes expressed at the
      late stage of differentiation can regulate cell behaviors and functions. To
      determine the optimal timing of key gene delivery, we sequentially transfected
      human mesenchymal stem cells (hMSCs). This method can easily control osteogenesis
      of stem cells. hMSCs were first transfected with RUNX2 and SP7 using poly(lactic
      co-glycolic acid) nanoparticles to induce osteogenesis, and then with ATF4 after
      5, 7, and 14 days. Prior to transfecting hMSCs with all three genes, each gene
      was individually transfected and its expression was monitored. Transfection of
      these genes was confirmed by RT-PCR, Western blotting, and confocal microscopy.
      The pDNAs entered the nuclei of hMSCs, and RUNX2 and SP7 proteins were translated
      and triggered osteogenesis. Second, the ATF4 gene was delivered when cells were
      at the pre-osteoblasts stage. To induce the osteogenesis of hMSCs, the optimal
      timing of ATF4 gene delivery was 14 days after RUNX2/SP7 transfection.
      Experiments in 2- and 3-dimensional culture systems confirmed that transfection
      of ATF4 at 14 days after RUNX2/SP7 promoted osteogenic differentiation of hMSCs.

PMID- 29362503
TI  - Alloantigen expression on malignant cells and healthy host tissue influences
      graft-versus-tumor reactions after allogeneic hematopoietic stem cell
      transplantation.
AB  - Durable remissions of hematological malignancies regularly observed following
      allogeneic hematopoietic stem cell transplantation (aHSCT) are due to the
      conditioning regimen, as well as an immunological phenomenon called graft-versus
      leukemia (GVL) or graft-versus-tumor (GVT) effect. The development of GVL is
      closely linked to graft-versus-host disease (GVHD), the main side effect
      associated with aHSCT. Both, GVHD and GVL are mediated by donor T cells that are
      initially activated by antigen-presenting cells that present recipient-derived
      alloantigens in the context of either matched or mismatched MHC class I
      molecules. Using murine models of aHSCT we show that ubiquitously expressed minor
      histocompatibility alloantigens (mHAg) are no relevant target for GVT effects.
      Interestingly, certain ubiquitously expressed MHC alloantigens augmented GVT
      effects early after transplantation, while others did not. The magnitude of GVT
      effects correlated with tumor infiltration by CD8+ cytotoxic T cells and tumor
      cell apoptosis. Furthermore, the immune response underlying GVHD and GVT was
      oligoclonal, highlighting that immunodominance is an important factor during
      alloimmune responses. These results emphasize that alloantigen expression on non
      hematopoietic tissues can influence GVT effects in a previously unrecognized
      fashion. These findings bear significance for harnessing optimal GVL effects in
      patients receiving aHSCT.

PMID- 29362502
TI  - Lethal mutagenesis of an RNA plant virus via lethal defection.
AB  - Lethal mutagenesis is an antiviral therapy that relies on increasing the viral
      mutation rate with mutagenic nucleoside or base analogues. Currently, the
      molecular mechanisms that lead to virus extinction through enhanced mutagenesis
      are not fully understood. Increasing experimental evidence supports the lethal
      defection model of lethal mutagenesis of RNA viruses, where replication-competent
      defectors drive infective virus towards extinction. Here, we address lethal
      mutagenesis in vivo using 5-fluorouracil (5-FU) during the establishment of
      tobacco mosaic virus (TMV) systemic infections in N. tabacum. The results show
      that 5-FU decreased the infectivity of TMV without affecting its viral load.
      Analysis of molecular clones spanning two genomic regions showed an increase of
      the FU-related base transitions A -> G and U -> C. Although the mutation
      frequency or the number of mutations per molecule did not increase, the
      complexity of the mutant spectra and the distribution of the mutations were
      altered. Overall, our results suggest that 5-FU antiviral effect on TMV is
      associated with the perturbation of the mutation-selection balance in the genomic
      region of the RNA-dependent RNA polymerase (RdRp). Our work supports the lethal
      defection model for lethal mutagenesis in vivo in a plant RNA virus and opens the
      way to study lethal mutagens in plant-virus systems.

PMID- 29362504
TI  - Secondary malignancies and survival outcomes after autologous stem cell
      transplantation for follicular lymphoma in the pre-rituximab and rituximab eras:
      a long-term follow-up analysis from the Spanish GELTAMO registry.

PMID- 29362505
TI  - Polypharmacy and adverse drug events among propensity score matched privately
      insured persons with and without spinal cord injury.
AB  - STUDY DESIGN: Retrospective quasi-experimental design. OBJECTIVES: To compare the
      incidence of adverse drug events (ADEs) between persons with and without spinal
      cord injury (SCI), while controlling for all potential and available risk
      factors. SETTING: A commercially available claims dataset consisting of ~170
      million patient cases in the United States between 2012 and 2013. METHODS:
      Participants (aged 18-64 years) included 2779 persons with polypharmacy and
      traumatic or non-traumatic SCI and 2779 propensity score-matched persons with
      polypharmacy without SCI. The cohorts were matched using demographic variables
      including number of concomitant prescriptions, comorbidities, hospital
      admissions, age, gender, and geographic region. Inpatient and outpatient claims
      records containing 395 distinct IDC-9 codes indicative of ADEs were extracted.
      Incidence and frequency of ADEs were compared between groups using logistic and
      Poisson regression, respectively. RESULTS: Persons with SCI were significantly
      more likely to experience an ADE than matched controls (Odds Ratio = 1.45, p <
      0.0001). Among persons with ADEs (n = 1552), individuals with SCI experienced
      fewer ADEs over time than matched controls (Incidence Rate Ratio = 0.91, p <
      0.0001). CONCLUSIONS: While persons with SCI and polypharmacy are at a greater
      risk for experiencing an ADE, their medical care after an ADE may be better
      managed than that of a matched control population. There may be a need for
      practice guidelines that facilitate proactive identification of persons with SCI
      at the highest risk of ADE. Steps may then be taken to mitigate risk, in contrast
      to current practice trends that appear to take a reactive approach after an ADE
      has occurred.

PMID- 29362506
TI  - Evolutionary loss and replacement of Buchnera, the obligate endosymbiont of
      aphids.
AB  - Symbiotic interactions between organisms create new ecological niches. For
      example, many insects survive on plant-sap with the aid of maternally transmitted
      bacterial symbionts that provision essential nutrients lacking in this diet.
      Symbiotic partners often enter a long-term relationship in which the co
      evolutionary fate of lineages is interdependent. Obligate symbionts that are
      strictly maternally transmitted experience genetic drift and genome degradation,
      compromising symbiont function and reducing host fitness unless hosts can
      compensate for these deficits. One evolutionary solution is the acquisition of a
      novel symbiont with a functionally intact genome. Whereas almost all aphids host
      the anciently acquired bacterial endosymbiont Buchnera aphidicola
      (Gammaproteobacteria), Geopemphigus species have lost Buchnera and instead
      contain a maternally transmitted symbiont closely related to several known insect
      symbionts from the bacterial phylum Bacteroidetes. A complete genome sequence
      shows the symbiont has lost many ancestral genes, resulting in a genome size
      intermediate between that of free-living and symbiotic Bacteroidetes. The
      Geopemphigus symbiont retains biosynthetic pathways for amino acids and vitamins,
      as in Buchnera and other insect symbionts. This case of evolutionary replacement
      of Buchnera provides an opportunity to further understand the evolution and
      functional genomics of symbiosis.

PMID- 29362507
TI  - Multiple colonist pools shape fiddler crab-associated bacterial communities.
AB  - Colonization is a key component of community assembly because it continuously
      contributes new species that can potentially establish and adds individuals to
      established populations in local communities. Colonization is determined by the
      regional species pool, which is typically viewed as stable at ecological time
      scales. Yet, many natural communities including plants, birds and microbes, are
      exposed to several distinct and dynamic sources of colonists and how multiple
      colonist pools interact to shape local communities remains unclear. Using a 16S
      rRNA amplicon survey, we profiled bacteria within surface, subsurface and burrow
      sediments and assessed their role as colonist pools for fiddler crab-associated
      bacteria. We found significant differences in composition among sediment types,
      driven by halophilic taxa in the surface, and different Desulfobacteraceae taxa
      in the subsurface and burrow. Bacteria from burrow sediment colonized the crab
      carapace whereas gut bacterial communities were colonized by burrow and surface
      sediment bacteria. Despite distinct colonist pools influencing gut bacteria,
      variation in composition across gut samples did not lead to significant clusters.
      In contrast, carapace bacterial communities clustered in six distinct groups
      loosely associated with crab species. Our findings suggest that multiple colonist
      pools can influence local communities but factors explaining variation in
      community composition depend on local habitats. Recognizing multiple colonist
      pools expands our understanding of the interaction between regional and local
      processes driving community structure and diversity.

PMID- 29362508
TI  - Inhibition of RM-1 prostate carcinoma and eliciting robust immune responses in
      the mouse model by using VEGF-M2-GnRH3-hinge-MVP vaccine.
AB  - GnRH and VEGF have been investigated as prostate carcinoma enhancers that support
      tumor spread and progression. Although both have documented roles in prostate
      carcinoma and many cancer types, the weak immunogenicity of these peptides has
      remained a major challenge for use in immunotherapy. Here, we describe a novel
      strategy to inhibit GnRH and VEGF production and assess the effect on the immune
      responses against these hormones using the RM-1 prostate cancer model. We
      designed a novel recombinant fusion protein which combined GnRH and VEGF as a
      vaccine against this tumor. The newly constructed fusion protein hVEGF121-M2
      GnRH3-hinge-MVP contains the human vascular endothelial growth factor (hVEGF121)
      and three copies of GnRH in sequential linear alignment and T helper epitope MVP
      as an immunogenic vaccine. The effectiveness of the vaccine in eliciting an
      immune response and attenuating the prostate tumor growth was evaluated. Results
      showed that administration of a new vaccine effectively elicited humoral and
      cellular immune responses. We found that, a novel fusion protein, hVEGF121-M2
      GnRH3-hinge-MVP, effectively inhibited growth of RM-1 prostate model and
      effectively promoted immune response. In conclusion, hVEGF121-M2-GnRH3-hinge-MVP
      is an effective dual mechanism tumor vaccine that limits RM-1 prostate growth.
      This vaccine may be a promising strategy for the treatment of hormone refractory
      prostate malignancies.

PMID- 29362509
TI  - Structure-based selection of human metabolite binding P4 pocket of DRB1*15:01 and
      DRB1*15:03, with implications for multiple sclerosis.
AB  - Binding of small molecules in the human leukocyte antigen (HLA) peptide-binding
      groove may result in conformational changes of bound peptide and an altered
      immune response, but previous studies have not considered a potential role for
      endogenous metabolites. We performed virtual screening of the complete Human
      Metabolite Database (HMDB) for docking to the multiple sclerosis (MS) susceptible
      DRB1*15:01 allele and compared the results to the closely related yet non
      susceptible DRB1*15:03 allele; and assessed the potential impact on binding of
      human myelin basic peptide (MBP). We observed higher energy scores for metabolite
      binding to DRB1*15:01 than DRB1*15:03. Structural comparison of docked
      metabolites with DRB1*15:01 and DRB1*15:03 complexed with MBP revealed that
      PhenylalanineMBP92 allows binding of metabolites in the P4 pocket of DRB1*15:01
      but ValineMBP89 abrogates metabolite binding in the P1 pocket. We observed
      differences in the energy scores for binding of metabolites in the P4 pockets of
      DRB1*15:01 vs. DRB1*15:03 suggesting stronger binding to DRB1*15:01. Our study
      confirmed that specific, disease-associated human metabolites bind effectively
      with the most polymorphic P4 pocket of DRB1*15:01, the primary MS susceptible
      allele in most populations. Our results suggest that endogenous human metabolites
      bound in specific pockets of HLA may be immunomodulatory and implicated in
      autoimmune disease.

PMID- 29362510
TI  - Choriodecidual leukocytes display a unique gene expression signature in
      spontaneous labor at term.
AB  - Prior to and during the process of human labor, maternal circulating leukocytes
      infiltrate the maternal-fetal interface (choriodecidua) and become activated
      resembling choriodecidual leukocytes. Since, there is no evidence comparing
      maternal circulating and choriodecidual leukocytes, herein, we characterized
      their transcriptome and explored the biological processes enriched in
      choriodecidual leukocytes. From women undergoing spontaneous term labor we
      isolated circulating and choriodecidual leukocytes, performed microarray analysis
      (n = 5) and qRT-PCR validation (n = 9) and interaction network analysis with up
      regulated genes. We found 270 genes up-regulated and only 17 genes down-regulated
      in choriodecidual leukocytes compared to maternal circulating leukocytes. The
      most up-regulated genes were CCL18, GPNMB, SEPP1, FN1, RNASE1, SPP1, C1QC, and
      PLTP. The biological processes enriched in choriodecidual leukocytes were cell
      migration and regulation of immune response, chemotaxis, and humoral immune
      responses. Our results show striking differences between the transcriptome of
      choriodecidual and maternal circulating leukocytes. Choriodecidual leukocytes are
      enriched in immune mediators implicated in the spontaneous process of labor at
      term.

PMID- 29362511
TI  - Neuropsychiatric Phenotypes Produced by GABA Reduction in Mouse Cortex and
      Hippocampus.
AB  - Whereas cortical GAD67 reduction and subsequent GABA level decrease are
      consistently observed in schizophrenia and depression, it remains unclear how
      these GABAergic abnormalities contribute to specific symptoms. We modeled
      cortical GAD67 reduction in mice, in which the Gad1 gene is genetically ablated
      from ~50% of cortical and hippocampal interneurons. Mutant mice showed a
      reduction of tissue GABA in the hippocampus and cortex including mPFC, and
      exhibited a cluster of effort-based behavior deficits including decreased home
      cage wheel running and increased immobility in both tail suspension and forced
      swim tests. Since saccharine preference, progressive ratio responding to food,
      and learned helplessness task were normal, such avolition-like behavior could not
      be explained by anhedonia or behavioral despair. In line with the prevailing view
      that dopamine in anterior cingulate cortex (ACC) plays a role in evaluating
      effort cost for engaging in actions, we found that tail-suspension triggered
      dopamine release in ACC of controls, which was severely attenuated in the mutant
      mice. Conversely, ACC dopamine release by progressive ratio responding to reward,
      during which animals were allowed to effortlessly perform the nose-poking, was
      not affected in mutants. These results suggest that cortical GABA reduction
      preferentially impairs the effort-based behavior which requires much effort with
      little benefit, through a deficit of ACC dopamine release triggered by high
      effort cost behavior, but not by reward-seeking behavior. Collectively, a subset
      of negative symptoms with a reduced willingness to expend costly effort, often
      observed in patients with schizophrenia and depression, may be attributed to
      cortical GABA level reduction.

PMID- 29362512
TI  - Dopaminergic Genetic Variation Influences Aripiprazole Effects on Alcohol Self
      Administration and the Neural Response to Alcohol Cues in a Randomized Trial.
AB  - Dopamine (DA) signaling regulates many aspects of Alcohol Use Disorder (AUD).
      However, clinical studies of dopaminergic medications, including the DA partial
      agonist aripiprazole (APZ), have been inconsistent, suggesting the possibility of
      a pharmacogenetic interaction. This study examined whether variation in DA
      related genes moderated APZ effects on reward-related AUD phenotypes. The
      interacting effects of APZ and a variable number tandem repeat (VNTR)
      polymorphism in DAT1/SLC6A3 (the gene encoding the DA transporter (DAT)) were
      tested. In addition, interactions between APZ and a genetic composite comprising
      the DAT1 VNTR and functional polymorphisms in catechol-O-methyltransferase
      (COMT), DRD2, and DRD4 were evaluated. Ninety-four non-treatment-seeking
      individuals with AUD were genotyped for these polymorphisms, randomized to APZ
      (titrated to 15 mg) or placebo for 8 days, and underwent an fMRI alcohol cue
      reactivity task (day 7; n=81) and a bar lab paradigm (day 8). Primary outcomes
      were alcohol cue-elicited ventral striatal (VS) activation and the number of
      drinks consumed in the bar lab. DAT1 genotype significantly moderated medication
      effects, such that APZ, relative to placebo, reduced VS activation and bar-lab
      drinking only among carriers of the DAT1 9-repeat allele, previously associated
      with lower DAT expression and greater reward-related brain activation. The
      genetic composite further moderated medication effects, such that APZ reduced the
      primary outcomes more among individuals who carried a larger number of DAT1,
      COMT, DRD2, and DRD4 alleles associated with higher DA tone. Taken together,
      these data suggest that APZ may be a promising AUD treatment for individuals with
      a genetic predisposition to higher synaptic DA tone.

PMID- 29362479
TI  - Molecular mechanisms of cell death: recommendations of the Nomenclature Committee
      on Cell Death 2018.
AB  - Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has
      formulated guidelines for the definition and interpretation of cell death from
      morphological, biochemical, and functional perspectives. Since the field
      continues to expand and novel mechanisms that orchestrate multiple cell death
      pathways are unveiled, we propose an updated classification of cell death
      subroutines focusing on mechanistic and essential (as opposed to correlative and
      dispensable) aspects of the process. As we provide molecularly oriented
      definitions of terms including intrinsic apoptosis, extrinsic apoptosis,
      mitochondrial permeability transition (MPT)-driven necrosis, necroptosis,
      ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death,
      lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell
      death, cellular senescence, and mitotic catastrophe, we discuss the utility of
      neologisms that refer to highly specialized instances of these processes. The
      mission of the NCCD is to provide a widely accepted nomenclature on cell death in
      support of the continued development of the field.

PMID- 29362515
TI  - Increased Risk of the APOB rs11279109 Polymorphism for CHD among the Kuwaiti
      Population.
AB  - Background: Coronary heart disease (CHD) is among the leading causes of death in
      Kuwait. This case-control study investigated the genetic association of APOB
      rs11279109 with CHD in Kuwaitis. Methods: The polymorphism was genotyped in 734
      Kuwaiti samples by direct amplification. Statistical analysis with genetic
      modeling was used to assess its association with CHD. Results: A statistically
      significant association (P < 0.001) between the rs11279109 DD genotype (OR: 2.43,
      CI: 1.34-4.41) with CHD was observed. A codominant genetic model revealed a 2.69
      risk increase (CI: 1.57-4.61) for the DD genotype (P = 0.009) independent of age,
      sex, BMI, smoking, hypercholesterolemia, and ethnicity suggesting APOB rs11279109
      as an indicator for the increased risk of CHD. Conclusion: The DD genotype may
      explain molecular mechanisms that underline increased LDL oxidation leading to
      arthrosclerosis. The findings emphasize the need to identify genetic markers
      specific to the CHD patient ethnic group in order to improve prognosis and help
      in early diagnosis and prevention.

PMID- 29362516
TI  - Introduction to serial reviews: Current progress in covalent modification of
      biomolecules by compounds in food or oxidatively generated compounds - its
      relevance to biological functions.

PMID- 29362518
TI  - A fluorescent metal-sensor study provides evidence for iron transport by
      transcytosis in the intestinal epithelial cells.
AB  - Iron transport across the intestinal epithelium is facilitated by the divalent
      metal transporter 1 (DMT1) on the brush border membrane (BBM). The fluorescent
      metal sensor calcein, which is hydrophilic, membrane-impermeable and quenched by
      chelation with iron, was used to test our hypothesis that intestinal iron
      absorption is through the endocytic processes and is involved in a pathway where
      BBM-derived vesicles fuse with basolateral membrane (BLM)-derived vesicles. To
      monitor the flux of iron via transcytosis, Caco-2 cells were employed as a
      polarized cell layer in Transwell chambers. When calcein was added to the basal
      chamber along with apo-transferrin (apo-Tf), calcein rapidly underwent
      endocytosis and co-localized with apo-Tf. Calcein was quenched by adding an iron
      ascorbate complex and then restored by adding 2,2'-dipyridyl into the apical
      chamber. These results were confirmed by live-cell imaging. When hemin from the
      apical surface and calcein from the basal chamber were added to the Caco-2 cells,
      internalization of DMT1 and quenching of calcein were not observed until 2 h
      later. These results indicated that absorbed hemin required processing before
      hemin-derived iron was available to BLM-derived vesicles. These studies suggest
      that iron is transported in Caco-2 cells by transcytosis with apical-derived
      vesicles that are fused to BLM-derived vesicles.

PMID- 29362519
TI  - Visfatin Triggers Anorexia and Body Weight Loss through Regulating the
      Inflammatory Response in the Hypothalamic Microglia.
AB  - Visfatin is an adipokine that is secreted from adipose tissue, and it is involved
      in a variety of physiological processes. In particular, visfatin has been
      implicated in metabolic diseases, such as obesity and type 2 diabetes, which are
      directly linked to systemic inflammation. However, the potential impacts of
      visfatin on the hypothalamic control of energy homeostasis, which is involved in
      microglial inflammation, have not fully been investigated. In this study, we
      found that treatment with exogenous recombinant visfatin protein led to the
      activation of the inflammatory response in a microglial cell line. In addition,
      we observed that central administration of visfatin led to the activation of
      microglia in the hypothalamus. Finally, we found that visfatin reduced food
      intake and body weight through activating POMC neurons in association with
      microglia activation in mice. These findings indicate that elevation of central
      visfatin levels may be associated with homeostatic feeding behavior in response
      to metabolic shifts, such as increased adiposity following inflammatory processes
      in the hypothalamus.

PMID- 29362517
TI  - Abundance of DNA adducts of 4-oxo-2-alkenals, lipid peroxidation-derived highly
      reactive genotoxins.
AB  - Reactive oxygen species and their reaction products can damage DNA to form
      mutagenic lesions. Among the reactive species, lipid peroxidation-derived
      aldehydes react with nucleobases and form bulky exocyclic adducts. Many types of
      aldehyde-derived DNA adducts have been characterized, identified and detected in
      vitro and in vivo, whereas relative quantitative and pathophysiological
      contributions of each adduct still remain unclear. In recent years, an abundant
      class of DNA adducts derived from 4-oxo-2-alkenals have been identified, in
      addition to classic aldehyde-derived adducts. The presence of 4-oxo-2-alkenal
      derived DNA adducts associated with age-related diseases has been revealed in
      rodents and humans. In vitro studies have demonstrated that 4-oxo-2-alkenals, as
      compared with other classes of lipid peroxidation-derived aldehydes, are highly
      reactive with nucleobases. It has been generally recognized that 4-oxo-2-alkenals
      are generated through oxidative degradation of the corresponding 4-hydroperoxy-2
      alkenals, homolytic degradation products of polyunsaturated fatty acid
      hydroperoxides. Our recent results have also shown an alternative pathway for the
      formation of 4-oxo-2-alkenals, in which 2-alkenals could undergo the metal
      catalyzed autoxidation resulting in the formation of the corresponding 4-oxo-2
      alkenals. This review summarizes the basis of the formation of lipid peroxidation
      derived genotoxic aldehydes and their covalent adduction to nucleobases,
      especially focusing on the abundance of 4-oxo-2-alkenal-derived DNA adducts.

PMID- 29362520
TI  - Role of Cathepsin S in Periodontal Inflammation and Infection.
AB  - Cathepsin S is a cysteine protease and regulator of autophagy with possible
      involvement in periodontitis. The objective of this study was to investigate
      whether cathepsin S is involved in the pathogenesis of periodontal diseases.
      Human periodontal fibroblasts were cultured under inflammatory and infectious
      conditions elicited by interleukin-1beta and Fusobacterium nucleatum,
      respectively. An array-based approach was used to analyze differential expression
      of autophagy-associated genes. Cathepsin S was upregulated most strongly and thus
      further studied in vitro at gene and protein levels. In vivo, gingival tissue
      biopsies from rats with ligature-induced periodontitis and from periodontitis
      patients were also analyzed at transcriptional and protein levels. Multiple gene
      expression changes due to interleukin-1beta and F. nucleatum were observed in
      vitro. Both stimulants caused a significant cathepsin S upregulation. A
      significantly elevated cathepsin S expression in gingival biopsies from rats with
      experimental periodontitis was found in vivo, as compared to that from control.
      Gingival biopsies from periodontitis patients showed a significantly higher
      cathepsin S expression than those from healthy gingiva. Our findings provide
      original evidence that cathepsin S is increased in periodontal cells and tissues
      under inflammatory and infectious conditions, suggesting a critical role of this
      autophagy-associated molecule in the pathogenesis of periodontitis.

PMID- 29362522
TI  - Next-generation morphological character discovery and evaluation: an X-ray micro
      CT enhanced revision of the ant genus Zasphinctus Wheeler (Hymenoptera,
      Formicidae, Dorylinae) in the Afrotropics.
AB  - New technologies for imaging and analysis of morphological characters offer
      opportunities to enhance revisionary taxonomy and better integrate it with the
      rest of biology. In this study, we revise the Afrotropical fauna of the ant genus
      Zasphinctus Wheeler, and use high-resolution X-ray microtomography (micro-CT) to
      analyse a number of morphological characters of taxonomic and biological
      interest. We recognise and describe three new species: Z. obamaisp. n., Z.
      sarowiwaisp. n., and Z. wilsonisp. n. The species delimitations are based on the
      morphological examination of all physical specimens in combination with 3D scans
      and volume reconstructions. Based on this approach, we present a new taxonomic
      discrimination system for the regional fauna that consists of a combination of
      easily observable morphological characters visible at magnifications of around 80
      100 *, less observable characters that require higher magnifications, as well as
      characters made visible through virtual dissections that would otherwise require
      destructive treatment. Zasphinctus are rarely collected ants and the material
      available to us is comparatively scarce. Consequently, we explore the use of
      micro-CT as a non-invasive tool for the virtual examination, manipulation, and
      dissection of such rare material. Furthermore, we delineate the treated species
      by providing a diagnostic character matrix illustrated by numerous images and
      supplement that with additional evidence in the form of stacked montage images,
      3D PDFs and 3D rotation videos of scans of major body parts and full body (in
      total we provide 16 stacked montage photographs, 116 images of 3D
      reconstructions, 15 3D rotation videos, and 13 3D PDFs). In addition to the
      comparative morphology analyses used for species delimitations, we also apply
      micro-CT data to examine certain traits, such as mouthparts, cuticle thickness,
      and thoracic and abdominal muscles in order to assess their taxonomic usefulness
      or gain insights into the natural history of the genus. The complete datasets
      comprising the raw micro-CT data, 3D PDFs, 3D rotation videos, still images of 3D
      models, and coloured montage photos have been made available online as cybertypes
      (Dryad, http://dx.doi.org/10.5061/dryad.4s3v1).

PMID- 29362523
TI  - Editorial.

PMID- 29362521
TI  - Granulocyte Colony-Stimulating Factor and Its Potential Application for Skeletal
      Muscle Repair and Regeneration.
AB  - Granulocyte colony-stimulating factor (G-CSF) was originally discovered in the
      context of hematopoiesis. However, the identification of the G-CSF receptor (G
      CSFR) being expressed outside the hematopoietic system has revealed wider roles
      for G-CSF, particularly in tissue repair and regeneration. Skeletal muscle
      damage, including that following strenuous exercise, induces an elevation in
      plasma G-CSF, implicating it as a potential mediator of skeletal muscle repair.
      This has been supported by preclinical studies and clinical trials investigating
      G-CSF as a potential therapeutic agent in relevant disease states. This review
      focuses on the growing literature associated with G-CSF and G-CSFR in skeletal
      muscle under healthy and disease conditions and highlights the current
      controversies.

PMID- 29362524
TI  - Honduranura centraliamericana gen. n. et sp. n. from Central America (Collembola,
      Neanuridae, Neanurinae).
AB  - Honduranuragen. n. and the type species H. centraliamericanasp. n. are described
      and illustrated. The new genus shows the characters of Sensillanurini Cassagnau,
      1983 tribe and is distinguished by the fusion of cephalic and abdominal
      tubercles: clypeal with antennofrontal and dorsointernal with dorsoexternal on
      head; presence of fused tubercles on each side of abdominal segment V. Most of
      the tubercles bear strong subcuticular reticulation. A key for the genera of the
      tribe Sensillanurini is provided.

PMID- 29362525
TI  - New species and records of terrestrial slugs from East Africa (Gastropoda,
      Urocyclidae, Veronicellidae, Agriolimacidae).
AB  - New and little-known terrestrial slugs are dealt with based on extensive
      collections made in East Africa (Kenya, Tanzania, and Uganda) 1993-2007. This
      account deals primarily with larger species from forests in the Eastern Arc
      Mountains of Tanzania. In Veronicellidae, Pseudoveronicella Germain, 1908 is
      extended to Tanzania by P. (Hoffmannia) zootoca tanzaniensis subsp. n. in the
      Udzungwa Mts. In Urocyclidae, Dendrolimax parensissp. n. is described from the
      Pare Mts. and Leptichnoides avisexcrementissp. n. is described from the Uluguru
      Mts. In Urocyclinae, Tanzalimax tattersfieldigen. & sp. n. is described from the
      Usambara Mts., Tanzalimax seddonaegen. & sp. n. from the Uluguru Mts., and
      Udzungwalimax suminisgen. & sp. n. from the Udzungwa Mts. In addition, the ill
      defined genus Atrichotoxon Simroth, 1910 is discussed and the little-known
      Dendrolimax leprosus Pollonera, 1906 is reported from Uganda. In Agriolimacidae,
      a species of Deroceras Rafinesque, 1820 is reported for the first time from
      southern Tanzania. The taxonomic attribution and significance of each discovery
      is discussed.

PMID- 29362526
TI  - New species of Indocloeon Muller-Liebenau from South-East Asia (Ephemeroptera,
      Baetidae).
AB  - One new species of Indocloeon Muller-Liebenau from Brunei, I. spathasetissp. n.,
      and one new species from Indonesia, I. timorensesp. n., are described and
      illustrated based on their larvae. The total number of known Indocloeon species
      increases from two to four and the generic attributes of the larvae are amended
      based on the examination of the new species. Results on the genetics of some
      species (COI) as well as comments on the distribution of I. indonesiae Kluge are
      also provided.

PMID- 29362527
TI  - Review of Stantonia Ashmead (Hymenoptera, Braconidae, Orgilinae) from Vietnam,
      China, Japan, and Russia, with descriptions of six new species.
AB  - The genus Stantonia Ashmead, 1904 (Hymenoptera, Braconidae, Orgilinae) is
      reviewed for Vietnam, China, Japan, and Russia. Six new species of the genus
      Stantonia are described and illustrated: Stantonia brevicaudata van Achterberg,
      sp. n., S. dickyyui van Achterberg & Long, sp. n., S. granulata Long & van
      Achterberg, sp. n., S. robustifemur van Achterberg & Long, sp. n., S. stilpnosoma
      Long & van Achterberg, sp. n., and S. vietnamica van Achterberg, sp. n. A new
      subgenus (Planitoniasubg. n.: type species Stantonia robustifemur van Achterberg
      & Long, sp. n.) is proposed for the species with a flat clypeus and face, and
      reduced vein r-m of the fore wing. Three species are newly recorded from Vietnam:
      Stantonia gracilis van Achterberg, 1987, S. sumatrana Enderlein, 1908, and S.
      tianmushana Chen, He & Ma, 2004. A key to species of Stantonia from Vietnam,
      China, Russia, and Japan is provided.

PMID- 29362528
TI  - The genus Gallerucida Motschulsky in Taiwan (Insecta, Coleoptera, Chrysomelidae,
      Galerucinae).
AB  - Species within the genus Gallerucida Motschulsky recorded in Taiwan are revised.
      Gallerucida bifasciata Motschulsky 1861 G. lutea Gressitt & Kimoto 1963 G.
      sauteri Chujo 1938 and G. shirozui Kimoto 1969 are redescribed. Sphenoraia chujoi
      Lee 2014 is proposed as a junior synonym of G. flaviventris (Baly 1861).
      Gallerucida thoracica (Jacoby 1888) is recorded as new for Taiwan and
      redescribed. Lectotypes are designated for Gallerucida nigrita Chujo 1935 G.
      sauteri Chujo 1938 and Eustetha thoracica Jacoby 1888. Biological notes are given
      on all Taiwanese species of Gallerucida.

PMID- 29362529
TI  - Two new Dolichothele Mello-Leitao, 1923 species from Brazil and Bolivia (Araneae,
      Theraphosidae).
AB  - Two new species of Dolichothele Mello-Leitao, 1923 are described from Brazil and
      Bolivia, D. mottaisp. n. from Distrito Federal and the state of Goias, Brazil,
      and D. camargorumsp. n. from the state of Rondonia, Brazil, and the La Paz
      region, Bolivia. Males of the two new species resemble Dolichothele bolivianum
      (Vol, 2001) in having a small subapical keel on the distal embolus and females in
      particular by the short spermatheca. Dolichothele bolivianum is redescribed, and
      its geographical distribution is herein restricted to Bolivia and the state of
      Mato Grosso in Brazil.

PMID- 29362530
TI  - Magadhaideus, a new genus of the tribe Plectoderini with the description of a new
      species from China (Hemiptera, Fulgoromorpha, Achilidae).
AB  - A new planthopper genus and species from China, Magadhaideus xiphos Long & Chen,
      gen. et sp. n. (Hemiptera: Fulgoromorpha: Achilidae: Plectoderini), is described
      and illustrated. A new combination, Magadhaideus cervina (Fennah, 1956), comb. n.
      transferred from Magadha Distant and a key to species of the new genus are also
      given.

PMID- 29362531
TI  - Hind wing variation in Leptura annularis complex among European and Asiatic
      populations (Coleoptera, Cerambycidae).
AB  - The ability to quantify morphological variation is essential for understanding
      the processes of species diversification. The geometric morphometrics approach
      allows reliable description of variation in animals, including insects. Here,
      this method was used to quantify the morphological variation among European and
      Asiatic populations of Leptura annularis Fabricius, 1801 and its closely related
      species L. mimica Bates, 1884, endemic for Japan and Sakhalin islands. Since the
      taxonomic status of these two taxa is differently interpreted by taxonomists,
      they are collectively called "Leptura annularis complex" in this paper. The
      analysis was based on the measurements of hind wings of 269 specimens from six
      populations from Europe and Asia. The level of morphological divergence between
      most of continental European and Asiatic populations was relatively small and
      proportional to the geographic distance between them. However, distinct
      morphotype was detected in Sakhalin Is. and Japan. These data confirm the
      morphological divergence of the endemic L. mimica species. Obtained results
      highlight the potential of the geometric morphometric method in studying
      morphological variation in beetles.

PMID- 29362532
TI  - Two new species of Thyridosmylus Kruger, 1913 from Madagascar (Neuroptera,
      Osmylidae).
AB  - The lance lacewing genus Thyridosmylus Kruger (Osmylidae: Spilosmylinae) is found
      in Madagascar and Southeast Asia. Two new Malagasy species are described herein,
      Thyridosmylus fuscomarginatus Xu, Wang & Winterton, sp. n., and Thyridosmylus
      longiprocessus Xu, Wang & Winterton, sp. n. A key to differentiate the Malagasy
      species of Thyridosmylus is provided.

PMID- 29362533
TI  - Aquatic dance flies (Diptera, Empididae, Clinocerinae and Hemerodromiinae) of
      Greece: species richness, distribution and description of five new species.
AB  - All records of aquatic dance flies (37 species in subfamily Clinocerinae and 10
      species in subfamily Hemerodromiinae) from the territory of Greece are
      summarized, including previously unpublished data and data on five newly
      described species (Chelifera horvati Ivkovic & Sinclair, sp. n., Wiedemannia
      iphigeniae Ivkovic & Sinclair, sp. n., W. ljerkae Ivkovic & Sinclair, sp. n., W.
      nebulosa Ivkovic & Sinclair, sp. n. and W. pseudoberthelemyi Ivkovic & Sinclair,
      sp. n.). The new species are described and illustrated, the male terminalia of
      Clinocera megalatlantica (Vaillant) are illustrated and the distributions of all
      species within Greece are listed. The aquatic Empididae fauna of Greece consists
      of 47 species, with the following described species reported for the first time:
      Chelifera angusta Collin, Hemerodromia melangyna Collin, Clinocera
      megalatlantica, Kowarzia plectrum (Mik), Phaeobalia dimidiata (Loew), W.
      (Chamaedipsia) beckeri (Mik), W. (Philolutra) angelieri Vaillant and W. (P.)
      chvali Joost. A key to species of aquatic Empididae of Greece is provided for the
      first time. Information related to the European Ecoregions in which species were
      found is given. Compared to the other studied countries in the Balkans, the Greek
      species assemblage is most similar to that of the Former Yugoslav Republic of
      Macedonia.

PMID- 29362534
TI  - Review of the genus Locastra Walker, 1859 from China, with descriptions of four
      new species (Lepidoptera, Pyralidae, Epipaschiinae).
AB  - The genus Locastra Walker, 1859 from China is reviewed. Of the five species
      treated, four species are described as new: L. nigrilineatasp. n., L. solivagasp.
      n., L. subtrapeziasp. n. and L. viridissp. n. A diagnosis of L. muscosalis
      (Walker, 1866) is given. Photographs of adults and the genitalia are provided,
      along with a key to the five Chinese species treated.

PMID- 29362535
TI  - Riparian Collembola (Hexapoda) communities of northern Moldova, Eastern Europe.
AB  - Collembola were studied in a well-preserved riverine section of the Prut River in
      the Republic of Moldova. The study was focused on species diversity and habitat
      preferences of the particular species at two localities. Riparian habitats of the
      Prut River near Braniste included open river bank, forest belt and meadow, and
      the shore of Lake Costesti-Stanca included meadow, pasture and shrub vegetation.
      In total 77 collembolan species were recorded, of which Neanura moldavica and
      Arrhopalites prutensis were endemic to Moldova. Comparative analyses showed a
      specific community composition at Braniste, with Anurida ellipsoides and
      Mesaphorura macrochaeta being abundant on the river bank and Hemisotoma
      thermophila in the meadow. In contrast, the forest plantation at the same
      locality was similar to the shrub-land in Costesti, with the common species
      Mesaphorura critica, M. yosii, Deutonura albella and Isotomiella minor.
      Hygrophilous species preferred the habitats of the river section in Braniste,
      with quiet backwaters, to the artificial shoreline of the large lake. Species
      diversity was relatively high in the natural meadow and forest in Braniste and
      also in shrub-land on the lake shore. The present study documented relatively
      high collembolan species diversity at the shoreline and running water sections in
      the upper catchment area of the Prut River in Moldova that involve naturally
      valuable inundated habitats of Eastern Europe.

PMID- 29362536
TI  - A new species of Rana from the Dabie Mountains in eastern China (Anura, Ranidae).
AB  - A new species Rana dabieshanensissp. n. is described from the Dabie Mountains in
      Anhui Province, China, based on morphological character differences and molecular
      analyses. The new species can be distinguished from its congeners by a
      combination of diagnostic characters. The results of phylogenetic analyses (based
      on 12s rRNA, 16s rRNA, ND2, Cyt b, RAG1, BDNF and Tyr) and genetic distances
      (based on Cyt b) indicate that the new species belongs to the Rana longicrus
      group, and is placed as the sister taxon to R. hanluica.

PMID- 29362537
TI  - The first record of Telemidae from Kenya, with the description of two new species
      (Arachnida, Araneae).
AB  - Two new species of Telemidae from Kenya are described: Guhua kakamegaensis Zhao &
      Li, gen. et sp. n., Apneumonella taitatavetaensis Zhao & Li, sp. n. Holotypes are
      deposited in the National Museum of Kenya in Nairobi, and all paratypes are
      deposited in the Institute of Zoology, Chinese Academy of Sciences in Beijing. A
      distribution map of Telemidae found in Kenya is presented.

PMID- 29362538
TI  - Seeking quantitative morphological characters for species identification in
      soldiers of Puerto Rican Heterotermes (Dictyoptera, Blattaria, Termitoidae,
      Rhinotermitidae).
AB  - Subterranean termites in the genus Heterotermes Froggatt (Rhinotermitidae:
      Heterotermitinae) are pantropical wood feeders capable of causing significant
      structural damage. The aim of this study was to investigate soldier morphological
      attributes in three Puerto Rican species of Heterotermes previously identified by
      sequencing of two mitochondrial genes and attributed to Heterotermes tenuis
      (Hagen), H. convexinotatus (Snyder) and H. cardini (Snyder). Soldiers (n = 156)
      were imaged and measured using the Auto-Montage image-stacking program. We
      demonstrated that Puerto Rican Heterotermes soldiers could not be identified to
      species level based upon seven morphometric indices or any combination thereof.
      Nor could differences in soldier head pilosity be used to discriminate species,
      in contrast to previous findings. However, previously described characters of the
      soldier tergal setae were reported to be useful in discriminating H. tenuis from
      both of its Puerto Rican congeners.

PMID- 29362539
TI  - Discovery of a most remarkable cave-specialized trechine beetle from southern
      China (Coleoptera, Carabidae, Trechinae).
AB  - Xuedytes bellus Tian & Huang, gen. et sp. n. is described from a limestone cave
      in Du'an Karst of Guangxi, a kingdom of cavernicolous trechine beetles in
      southern China. From a morphological point of view, Xuedytes Tian & Huang, gen.
      n. seems to be the most extremely cave-adapted trechines in the world.
      Superficially, it looks much like Giraffaphaenops Deuve, 2002 in general body
      shape, in particular the structure of the prothorax, but simultaneously it is
      similar to Dongodytes (s. str.) Deuve, 1993, based on elytral characters,
      including chaetotaxy. Hence the new genus seems to represent a lineage
      intermediate between Giraffaphaenops and Dongodytes (s. str.).

PMID- 29362540
TI  - A new species of Homoneura (Euhomoneura) from northern China (Diptera,
      Lauxaniidae).
AB  - Homoneura (Euhomoneura) yanqingensis sp. n. is described as new to science and
      Homoneura (E.) shatalkini Papp, 1984 is recorded from China for the first time.
      Photographs and illustrations are provided for both of these species, including
      genitalia. A key is provided to separate the Chinese species of the subgenus
      Euhomoneura.

PMID- 29362541
TI  - Southern limits of distribution of the intertidal gobies Chaenogobius annularis
      and C. gulosus support the existence of a biogeographic boundary in southern
      Japan (Teleostei, Perciformes, Gobiidae).
AB  - Understanding the distributional patterns of individual animal groups with
      respect to coastal topology and the local physical environment provides essential
      foundational frameworks for marine zoogeography. In the northwestern Pacific
      waters of Japan, the distributional pattern of some cool-temperate species of
      marine fishes suggests the existence of a biogeographic boundary corresponding to
      a long sandy shore on the eastern coast of Kyushu, southern Japan. The existence
      of this hypothetical biogeographic boundary was tested by mapping the southern
      distributional limit of two species of cool-temperate intertidal gobies,
      Chaenogobius annularis and C. gulosus, which are endemic to East Asia and common
      in rock pools within their range in the Japanese Archipelago. Distribution and
      abundance were assessed by survey of museum collections from south-east Kyushu
      (i.e., the entire coasts of Kagoshima and Miyazaki prefectures); and a
      quantitative survey of the abundance of these gobies in rock pools at various
      sites around the hypothesized boundary on the eastern coast of Kyushu, including
      the subtropical Tanega-shima Island. The museum collection survey showed
      different distribution patterns between the two species: C. annularis was
      distributed along the entire coasts of south-east Kyushu including subtropical
      islands, whereas C. gulosus was distributed along these coasts, including one
      site on a subtropical island, except for an area south of the hypothesized
      boundary on the eastern coast of Kyushu. The density and occurrence rates of C.
      annularis in rock pools decreased with latitude, it being absent from a
      subtropical island, and C. gulosus was not detected from sites south of the
      hypothesized boundary. The qualitative survey showed that the southernmost
      records of C. annularis and C. gulosus were the adjacent subtropical islands
      (Yaku-shima and Tanega-shima islands respectively), although the quantitative
      survey suggested that their normal range of distribution was limited to the
      southern part of the Kyushu mainland. A combination of qualitative and
      quantitative survey methods in the present study highlighted that the
      southernmost record of a certain species may not necessarily indicate the true
      limit of its distribution. The distribution of C. gulosus supports the existence
      of the hypothetical biogeographic boundary, and the different distribution
      patterns of the two species may be caused by differences in their early life
      histories.

PMID- 29362542
TI  - Three new species and the molecular phylogeny of Antipathozoanthus from the Indo
      Pacific Ocean (Anthozoa, Hexacorallia, Zoantharia).
AB  - In this study, three new species of macrocnemic zoantharians (Hexacorallia,
      Zoantharia) are described from localities in the Indo-Pacific Ocean including the
      Red Sea, the Maldives, Palau, and southern Japan: Antipathozoanthus obscurussp.
      n., A. remengesauisp. n., and A. cavernussp. n. Although the genus
      Antipathozoanthus is currently restricted to species living on antipatharians, A.
      obscurussp. n. is not associated with any living substrate and instead is found
      on coral reef carbonate substrate within narrow caves or cracks. The two new
      species that have association with antipatharians, A. remengesauisp. n. and A.
      cavernussp. n., can be distinguished by their relative coenenchyme development
      and the antipatharian species that each uses as substrate. Additionally, all new
      species described in this study have unique nuclear internal transcribed spacer
      region of ribosomal DNA (ITS-rDNA) sequences. Our results indicate that more
      phylogenetic studies focusing on increasing the numbers of species examined
      within each of the genera of Parazoanthidae are required in order to better
      understand the evolutionary history of substrate specificity within the family
      Parazoanthidae.

PMID- 29362543
TI  - A new species of Trichopeltis Pocock, 1894 from southern China, with a checklist
      and a distribution map of Trichopeltis species (Diplopoda, Polydesmida,
      Cryptodesmidae).
AB  - The millipede genus Trichopeltis Pocock, 1894 contains 12 described species
      including a new species from southern China described here. Trichopeltis
      sutcharitisp. n. can be distinguished from congeners by its gonopods that are
      strongly caudolaterally curved and have a prominent, high, curved, densely setose
      process on each coxa. An updated checklist and a distribution map are provided
      for all species of the genus.

PMID- 29362544
TI  - Two new species of Lobellini from Tianmu Mountain, China (Collembola,
      Neanuridae).
AB  - Three species of the subfamily Neanurinae (Collembola: Neanuridae) are recorded
      from Tianmu Mountain, Zhejiang Province, east China. Two of them, Lobellina
      fusasp. n. and Paralobella tianmunasp. n., are new to science and described in
      this paper. Lobellina fusasp. n. can be recognized by the presence of six teeth
      on mandible and the fusion of dorsointernal tubercles on the head. Paralobella
      tianmunasp. n. is characterized by a mandible with seven teeth, the lateral
      tubercle of Abd. II-III respectively with 7 (6+s) chaetae. Crossodonthina
      bidentata Luo & Chen, 2009 is widely distributed in the mountain from 300 to 1500
      m a.s.l.

PMID- 29362545
TI  - A missing piece in the puzzle: the presence of Euglossa viridissima in the Baja
      California Peninsula (Hymenoptera, Apidae).
AB  - Orchid bees are a conspicuous component of the neotropical bee fauna, with a few
      species reaching the northernmost natural distribution for the group in
      northwestern continental Mexico. Among them, Euglossa viridissima Friese is here
      reported for the first time in the Cape Region of the Baja California peninsula,
      Mexico, where no species of the group have been found previously. These records
      are presented, their biogeographical implications discussed, and some
      interpretations of the local factors that influence the bees is presented.

PMID- 29362546
TI  - Effects of habitat and time of day on flock size of Turkey Vultures in Cuba
      (Cathartes aura).
AB  - In agricultural landscapes, the Turkey Vulture Cathartes aura feeds mainly on
      carcases of domestic animals. In spring 2017, data on 214 flocks of Turkey
      vultures were collected in a road survey in Cuba (in total 2384 km). Turkey
      Vultures were found to be common accross Cuba, but flock size varied between
      habitats, reaching a maximum of 43 in valleys and 31 in agricultural landscapes
      with domestic animal farms. Vultures were active throughout the day, but the time
      of day did not significantly affect flock size. This study corroborates previous
      studies which suggested that carrion resources located in agricultural habitats
      and river valleys is crucial for the continued survival of this still abundant
      species. Changes in Cuba's socio-political system in the near future will likely
      impact agricultural practices, and this in turn will likely affect Turkey
      Vultures. Our study may serve as a baseline against which future population
      changes and flocking behaviour of Turkey Vultures can be compared.

PMID- 29362547
TI  - Ridleyandra merohmerea (Gesneriaceae), a new species from Kelantan, Peninsular
      Malaysia.
AB  - Ridleyandra merohmerea, a new species of Gesneriaceae, is described and
      illustrated. It is endemic in Peninsular Malaysia and known from a few
      populations along the Tuang River in the lowland dipterocarp forest of the Ulu
      Galas Forest Reserve in Kelantan, Peninsular Malaysia. Its conservation status is
      assessed as Critically Endangered.

PMID- 29362548
TI  - Nahuatlea: a new genus of compositae (Gochnatieae) from North America.
AB  - In the course of a detailed molecular study of the tribe Gochnatieae (Compositae:
      Gochnatioideae) it became apparent that the genus Gochnatia (sensu Cabrera) was
      not monophyletic but composed of a number of morphologically, geographically, and
      molecularly distinct clades. All but one of these clades had previously been
      recognized at the generic or sectional level and therefore had a name that could
      be applied. However, one clade, whose members are from Mexico and adjacent parts
      of the United States, had never been recognized as a distinct taxon. The Mexican
      clade is the sister group of the Caribbean clade which seems to indicate a
      dispersal event from Southern South America to Mexico and from Mexico to the
      Caribbean. Here we provide the Mexican clade with a genus name, Nahuatlea, and
      make the necessary new combinations. The name is derived from Nahuatl, the major
      indigenous language that is spoken in the area where most of the collections were
      gathered. A genus description, key to species, images, and a short, species
      descriptions, are provided.

PMID- 29362549
TI  - Morphological and anatomical evidence support a new wild cassava: Manihot fallax
      (Crotonoideae, Euphorbiaceae), from Mato Grosso, Brazil.
AB  - During the preparation of the taxonomic treatment of Manihot in the Midwest
      Region of Brazil, a new species was found. Manihot fallax M.J. Silva & L.S.
      Inocencio is described, illustrated and morphologically compared with similar
      simple-leaved species. The conservation status, geographic distribution
      (including map), ecology, phenology and notes about leaf anatomy of the new
      species are given. The synonymisation of M. robusta M. Mend. & T. B. Cavalc.
      under M. attenuata Mull. Arg. and lectotypes for M. attenuata and M.
      brachystachys Pax & K. Hoffm are also proposed. An emended description of M.
      attenuata is proposed as the original description is incomplete as it lacks
      information on the pistillate flowers, fruits and seeds.

PMID- 29362550
TI  - A new species and two new records of Quercus (Fagaceae) from northern Vietnam.
AB  - A new species, Quercus xuanlienensis Binh, Ngoc & Bon, is described from Xuan
      Lien Nature Reserve, Vietnam. The new species is morphologically similar to Q.
      edithiae Skan, in having 8-11 pairs of secondary veins, bowl-shaped cupules and
      ellipsoid to cylindrical-ellipsoid and basally convex nuts. It differs in having
      serrulate leaf margins only at apical 1/5-1/7, almost entire margins of bracts on
      cupule and much longer nuts. The species is also similar to Q. fleuryi Hickel &
      A. Camus in having leaves glabrous on both surfaces with only an apically
      serrulate margin but differs in having shorter petioles, cupules enclosing 1/5 of
      the nut and much longer nuts. In addition, Q. disciformis Chun & Tsiang. and Q.
      bella Chun & Tsiang., previously known from China, are newly recorded from Ba Vi
      National Park, Vietnam.

PMID- 29362551
TI  - The communities of terrestrial macrofungi in different forest types in vicinities
      of Khanty-Mansiysk (middle taiga zone of West Siberia).
AB  - Background: The diversity of macrofungi in the vicinities of Khanty-Mansiysk
      (Yugra, Russia) was surveyed using a method of permanent sampling plots. Ten
      plots, each consisting of a number of micro-plots, were established in several
      different communities ranging from old-growth mixed taiga forest to its
      derivatives in cutting succession and bogged areas. For more complete
      registration of the mycota, plots were supplemented with random walking routes
      directly nearby. Survey results were subjected to various quantitative analyses
      which allowed not only to evaluate the diversity of fungi but also to obtain
      valuable information on occurrence, abundance and ecology of individual species
      as well as community structure and its dynamics in the course of ecological
      succession. The paper reports the results of the first year of observations. New
      information: 460 species of terrestrial macrofungi revealed in a poorly explored
      area in middle taiga of West Siberia. The plot-based study revealed differences
      between communities of terrestrial macrofungi of old coniferous forests, their
      after-cutting secondary formations and bogged stages. The survey allowed to
      reveal records of 3 species listed in the Red Data Book of Russia and 9 species
      listed in the Red Data Book of Yugra.

PMID- 29362553
TI  - Standardized spider (Arachnida, Araneae) inventory of Hankoniemi, Finland.
AB  - Background: During a field course on spider taxonomy and ecology at the
      University of Helsinki, the authors had the opportunity to sample four plots with
      a dual objective of both teaching on field methods, spider identification and
      behaviour and uncovering the spider diversity patterns found in the southern
      coastal forests of Hankoniemi, Finland. As an ultimate goal, this field course
      intended to contribute to a global project that intends to uncover spider
      diversity patterns worldwide. With that purpose, a set of standardised methods
      and procedures was followed that allow the comparability of obtained data with
      numerous other projects being conducted across all continents. New information: A
      total of 104 species and 1997 adults was collected. Of these, 41 species (39%)
      were Linyphiidae and 13 (12%) Theridiidae. All other families had 6 or less
      species represented. Linyphiidae were also dominant in terms of adult individuals
      captured, with 1015 (51%), followed by 428 (21%) Lycosidae, 158 (8%)
      Tetragnathidae and 145 (7%) Theridiidae. All other families had less than 100
      individuals. The most abundant species were Neriene peltata, Alopecosa taeniata,
      Piratula hygrophila and Dismodicus elevatus, all with more than 100 individuals.
      All sites had between 56 and 62 species and between 445 and 569 individuals.

PMID- 29362552
TI  - Polychaetes of Greece: an updated and annotated checklist.
AB  - Background: The last annotated checklist of marine polychaetes in Greece was
      published in 2001. Since then, global taxonomic progress, combined with many new
      species records for Greece, required a thorough review of the taxonomic,
      nomenclatural and biogeographic status of the national species list. This
      checklist revises the status of all extant polychaete species reported from the
      Greek Exclusive Economic Zone since 1832. The work was undertaken as part of the
      efforts on compiling a national species inventory (Greek Taxon Information System
      initiative) in the framework of the LifeWatchGreece Research Infrastructure. New
      information: This checklist comprises an updated and annotated inventory of
      polychaete species in Greek waters, compiled from literature reports, online
      databases, museum collections and unpublished datasets. The list provides
      information on 836 species-level taxa from Greece, of which 142 are considered
      questionable. An additional 84 species reported in the past are currently
      considered absent from Greece; reasons for the exclusion of each species are
      given. Fourteen species are reported here for the first time from Greek waters.
      At least 52 species in the present list constitute in fact a complex of cryptic
      or pseudo-cryptic species. Forty-seven species are considered non-native to the
      area. In addition to the species-level taxa reported in this checklist, eleven
      genera have been recorded from Greece with no representatives identified to
      species level. One replacement name is introduced. For each species, a
      comprehensive bibliographic list of occurrence records in Greece and the synonyms
      used in these publications are provided as supplementary material. Where
      necessary, the taxonomic, nomenclatural or biogeographic status is discussed.
      Finally, the findings are discussed in the wider context of Mediterranean
      polychaete biogeography, taxonomic practice and worldwide research progress.

PMID- 29362554
TI  - Dataset of "true mangroves" plant species traits.
AB  - Background: Plant traits have been used extensively in ecology. They can be used
      as proxies for resource-acquisition strategies and facilitate the understanding
      of community structure and ecosystem functioning. However, many reviews and
      comparative analysis of plant traits do not include mangroves plants, possibly
      due to the lack of quantitative information available in a centralised form. New
      information: Here a dataset is presented with 2364 records of traits of "true
      mangroves" species, gathered from 88 references (published articles, books,
      theses and dissertations). The dataset contains information on 107 quantitative
      traits and 18 qualitative traits for 55 species of "true mangroves" (sensu
      Tomlinson 2016). Most traits refer to components of living trees (mainly leaves),
      but litter traits were also included.

PMID- 29362555
TI  - Seed plant diversity of different forest types in Liangshui National Natural
      Reserve.
AB  - Background: Thirty years ago, there was a monograph of vegetation and plant
      diversity in the region prepared by the Department of Forestry at the Northeast
      Forestry University (unpublished), but the variety of plants in the region has
      changed significantly over the past 30 years. In future years, the authors hope
      to publish a new monograph and this research is to prepare for this work. This
      study aimed at reporting the characteristics of plant diversity in five different
      forest types in Liangshui National Natural Reserve, China, each with three 25 *
      25 m tree quadrats, twelve 5 * 5 m wide shrub quadrats and twelve 1 * 1 m wide
      herbaceous quadrats. Censuses of each forest type were conducted in 2016. New
      information: The five main forest types presented differences in structure,
      diversity and species richness.

PMID- 29362556
TI  - Fauna of Cerambycidae (Insecta: Coleoptera) in Komaba Campus of the University of
      Tokyo, a highly urbanised area in Japan.
AB  - Urban green spaces play an important role in maintaining urban biodiversity in
      the Tokyo Metropolis, Japan. Plant-dependent insect assemblages such as
      Cerambycidae, in particular, are likely influenced by the existence of green
      spaces in Tokyo's urbanised environments. This study is the first comprehensive
      inventory of the cerambycid fauna in the Komaba Campus of the University of
      Tokyo. A cerambycid assemblage composed of a total of 25 species was recorded
      within the Komaba Campus site and compared to cerambycid assemblages in nine
      other green spaces distributed throughout Tokyo. The results indicated that the
      species number in the campus was similar to that recoded in a similar-sized green
      space in coastal Tokyo. Fewer cerambycid species were, however, found at the
      campus site than in larger-sized green spaces within Tokyo. Moreover, species
      compositions in urbanised areas were markedly different from those in
      suburbanised parks, mountains and forests within Tokyo.

PMID- 29362557
TI  - Aphyllophoroid fungi in insular woodlands of eastern Ukraine.
AB  - Background: Fungi play crucial roles in ecosystems and are among the species
      richest organism groups on Earth. However, knowledge on their occurrence lags
      behind the data for animals and plants. Recent analyses of fungal occurrence data
      from Western, Central and Northern Europe provided important insights into
      response of fungi to global warming. The consequences of the global changes for
      biodiversity on a larger geographical scale are not yet understood. Landscapes of
      Eastern Europe and particularly of eastern Ukraine, with their specific
      geological history, vegetation and climate, can add substantially new information
      about fungal diversity in Europe. New information: We describe the dataset and
      provide a checklist of aphyllophoroid fungi (non-gilled macroscopic
      Basidiomycota) from eastern Ukraine sampled in 16 areas between 2007 and 2011.
      The dataset was managed on the PlutoF biodiversity workbench
      (http://dx.doi.org/10.15156/BIO/587471) and can also be accessed via Global
      Biodiversity Information Facility (GBIF, parts of datasets
      https://doi.org/10.15468/kuspj6 and https://doi.org/10.15468/h7qtfd). This
      dataset includes 3418 occurences, namely 2727 specimens and 691 observations of
      fructifications belonging to 349 species of fungi. With these data, the digitised
      CWU herbarium (V. N. Karazin Kharkiv National University, Ukraine) doubled in
      size A most detailed description of the substrate's properties and habitat for
      each record is provided. The specimen records are supplemented by 26 nuclear
      ribosomal DNA ITS sequences and six 28S sequences. Additionally, 287 photographs
      depicting diagnostic macro- and microscopic features of fungal fruitbodies as
      well as studied habitats are linked to the dataset. Most of the specimens have at
      least one mention in literature and relevant references are displayed as
      associated with specimen data. In total, 16 publication references are linked to
      the dataset. The dataset sheds new light on the fungal diversity of Eastern
      Europe. It is expected to complement other public sources of fungal occurrence
      information on continental and global levels in addressing macroecological and
      biogeographical questions.

PMID- 29362559
TI  - Fluorine-19 Magnetic Resonance Imaging and Positron Emission Tomography of Tumor
      Associated Macrophages and Tumor Metabolism.
AB  - The presence of tumor-associated macrophages (TAMs) is significantly associated
      with poor prognosis of tumors. Currently, magnetic resonance imaging- (MRI-)
      based TAM imaging methods that use nanoparticles such as superparamagnetic iron
      oxide and perfluorocarbon nanoemulsions are available for quantitative monitoring
      of TAM burden in tumors. However, whether MRI-based measurements of TAMs can be
      used as prognostic markers has not been evaluated yet. In this study, we used
      positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG)
      as a radioactive tracer and fluorine-19- (19F-) MRI for imaging mouse breast
      cancer models to determine any association between TAM infiltration and tumor
      metabolism. Perfluorocarbon nanoemulsions were intravenously administered to
      track and quantify TAM infiltration using a 7T MR scanner. To analyze glucose
      uptake in tumors, 18F-FDG-PET images were acquired immediately after 19F-MRI.
      Coregistered 18F-FDG-PET and 19F-MR images enabled comparison of spatial patterns
      of glucose uptake and TAM distribution in tumors. 19F-MR signal intensities from
      tumors exhibited a strong inverse correlation with 18F-FDG uptake while having a
      significant positive correlation with tumor growth from days 2 to 7. These
      results show that combination of 19F-MRI and 18F-FDG-PET can improve our
      understanding of the relationship between TAM and tumor microenvironment.

PMID- 29362558
TI  - Mapping Extracellular pH of Gliomas in Presence of Superparamagnetic
      Nanoparticles: Towards Imaging the Distribution of Drug-Containing Nanoparticles
      and Their Curative Effect on the Tumor Microenvironment.
AB  - Since brain's microvasculature is compromised in gliomas, intravenous injection
      of tumor-targeting nanoparticles containing drugs (D-NPs) and superparamagnetic
      iron oxide (SPIO-NPs) can deliver high payloads of drugs while allowing MRI to
      track drug distribution. However, therapeutic effect of D-NPs remains poorly
      investigated because superparamagnetic fields generated by SPIO-NPs perturb
      conventional MRI readouts. Because extracellular pH (pHe) is a tumor hallmark,
      mapping pHe is critical. Brain pHe is measured by biosensor imaging of redundant
      deviation in shifts (BIRDS) with lanthanide agents, by detecting paramagnetically
      shifted resonances of nonexchangeable protons on the agent. To test the
      hypothesis that BIRDS-based pHe readout remains uncompromised by presence of SPIO
      NPs, we mapped pHe in glioma-bearing rats before and after SPIO-NPs infusion.
      While SPIO-NPs accumulation in the tumor enhanced MRI contrast, the pHe inside
      and outside the MRI-defined tumor boundary remained unchanged after SPIO-NPs
      infusion, regardless of the tumor type (9L versus RG2) or agent injection method
      (renal ligation versus coinfusion with probenecid). These results demonstrate
      that we can simultaneously and noninvasively image the specific location and the
      healing efficacy of D-NPs, where MRI contrast from SPIO-NPs can track their
      distribution and BIRDS-based pHe can map their therapeutic impact.

PMID- 29362560
TI  - Analysis of Factors Associated with the Severity of Acute Pancreatitis according
      to Etiology.
AB  - Background: The objective of this study was to determine the factors associated
      with severity of acute pancreatitis (AP) according to two major etiologies:
      alcohol and gallstones. Methods: We reviewed the medical records of consecutive
      patients who were admitted with AP between January 2003 and January 2013. A total
      of 905 patients with AP (660 alcohol-induced, 245 gallstone-induced) were
      enrolled. Among them, severe AP (SAP) occurred in 72 patients (53 alcohol
      induced, 19 gallstone-induced). Contributing factors between patients with and
      without SAP were analyzed according to the etiology. Results: Multivariate
      analysis demonstrated that current smoking, pancreatic necrosis, and bacteremia
      were associated with AP severity in both alcohol- and gallstone-induced AP.
      Pancreatic fluid collection was significantly associated with alcohol-induced SAP
      (p = 0.04), whereas dyslipidemia was significantly associated with gallstone
      induced SAP (p = 0.01). Body mass index was significantly correlated with the
      Bedside Index of Severity in Acute Pancreatitis score in both alcohol- and
      gallstone-induced AP (p = 0.03 and 0.01, resp.). Conclusions: Current smoking,
      pancreatic necrosis, and bacteremia can aggravate the clinical course of AP.
      Pancreatic fluid collection and dyslipidemia were associated with AP severity
      according to the different etiologies. Obesity may also be associated with AP
      severity in both etiologies.

PMID- 29362561
TI  - T Helper Lymphocyte and Mast Cell Immunohistochemical Pattern in Nonceliac Gluten
      Sensitivity.
AB  - Background and Aims: Nonceliac gluten sensitivity (NCGS) is a gluten-related
      emerging condition. Since few data about NCGS histopathology is available, we
      assessed the markers of lymphocyte and innate immunity activation. Materials and
      Methods: We retrieved duodenal biopsy samples of patients with NCGS diagnosis
      according to the Salerno criteria. We selected specimens of positive
      (seropositive celiac disease/Marsh 1-2 stage) and negative (normal microscopic
      picture) controls. Immunohistochemistry for CD3 (intraepithelial lymphocytes
      IELs), CD4 (T helper lymphocytes), CD8 (T cytotoxic lymphocytes), and CD1a/CD117
      (Langerhans/mast cells) was performed. ANOVA plus Bonferroni's tests were used
      for statistical analysis. Results: Twenty NCGS, 16 celiac disease, and 16
      negative controls were selected. CD3 in NCGS were higher than negative controls
      and lower than celiac disease (18.5 +/- 6.4, 11.9 +/- 2.8, and 40.8 +/- 8.1
      IELs/100 enterocytes; p < 0.001). CD4 were lower in NCGS than controls and celiac
      disease (31.0 +/- 22.1, 72.5 +/- 29.5, and 103.7 +/- 15.7 cells/mm2; p < 0.001).
      CD8 in NCGS were similar to negative controls, but lower than celiac disease
      (14.0 +/- 7.4 and 34.0 +/- 7.1 IELs/100 enterocytes, p < 0.001). CD117 were
      higher in NCGS than celiac disease and negative controls (145.8 +/- 49.9, 121.3
      +/- 13.1, and 113.5 +/- 23.4 cells/mm2; p = 0.009). Conclusions: The combination
      of CD4 and CD117, as well as IEL characterization, may be useful to support a
      clinical diagnosis of NCGS.

PMID- 29362563
TI  - The Hypoactivity Associated with the Repeated Exposure to Atrazine Is Related to
      Decreases in the Specific Binding to D1-DA Receptors in the Striatum of Rats.
AB  - The herbicide atrazine (ATR) has a potential toxic effect on the neuronal
      circuits of the brain, specifically on two major dopaminergic pathways: the
      nigrostriatal and mesolimbic circuits. In this work, we repeatedly exposed adult
      male Sprague-Dawley rats to 6 injections of 100 mg ATR/kg of body weight (for two
      weeks) and one saline injection two days after ATR administration. Locomotor
      activity was assessed for 15 minutes and/or 2 hours after ATR or saline injection
      and 2 months after the final ATR administration. The specific binding of [3H]
      SCH23390 to D1-DA receptors and that of [3H]-Spiperone to D2-DA receptors in the
      dorsal and ventral striatum were assessed 2 days and 2 months after ATR
      treatment. ATR administration resulted in immediate, short- and long-term
      hypoactivity and reduced specific binding of [3H]-SCH23390 in the dorsal striatum
      of rats evaluated 2 months after the last ATR injection. The specific binding of
      [3H]-SCH23390 in the ventral striatum and the specific binding of [3H]-Spiperone
      in the dorsal and ventral striatum remained unchanged at 2 days or 2 months after
      ATR treatment. These results, together with previous findings of our group,
      indicate that the nigrostriatal system is a preferential target for ATR exposure.

PMID- 29362562
TI  - Open Abdomen Management and Candida Infections: A Very Likely Link.
AB  - Objective: Laparostomy can be applied in trauma, abdominal sepsis, intra
      abdominal hypertension, or compartment syndrome. Systemic infections, especially
      if complicated by Candida, are associated with a high risk of mortality. Methods:
      This is a single-centre retrospective case series of 47 cases admitted to our
      Department, which required laparostomy procedure; we analyzed the type of
      surgery, temporary abdominal closure, duration of open abdomen, complications,
      SOFA score, mortality with Candida infections, and empirical or targeted
      antifungal therapy. Results: We found that patients with Candida infection were
      related with a statistically significant difference (p < 0.05) with a
      complication after OA closure, total complications, time elapsed after OA
      application, time spent on the first surgical OA application, type of temporary
      abdominal closure that is used, and duration of the open abdomen. The use of
      empirical and targeted antifungal therapy is related to the duration of open
      abdomen too. Conclusions: Management of the OA is often burdened by sepsis or
      septic shock, especially when complicated by Candida infection. Candida score is
      a validated tool to identify patients who can be treated empirically, but every
      situation must be considered on an individual basis.

PMID- 29362565
TI  - Staphylococcus aureus and Escherichia coli in Curd Cheese Sold in the
      Northeastern Region of South America.
AB  - The present study evaluated the microbiological and sanitary quality of curd
      cheese sold on the beaches of the Itaparica Island, Brazil, and verified whether
      a correlation exists between the commercialization conditions and the
      microbiological data. The research was performed between December 2015 and March
      2017. Sixty samples of rennet-containing cheese were collected to estimate the
      populations of mesophylls, psychrotrophic microorganisms, mold and yeast,
      Staphylococcus aureus, total coliforms, and Escherichia coli. An observational
      analysis was performed during the collection, using a checklist to verify the
      sellers' sanitary conditions and cheese marketing. A high nonconformity index was
      registered regarding aspects in the checklist. In the microbiological analyses,
      the number of mesophylls in raw and roasted samples ranged from 7,88 to 14,82 log
      CFU/mL, and those of psychrotrophs ranged from 2,80 to 3,84 log CFU/mL.
      Meanwhile, mold and yeast levels in the samples ranged from 8,06 to 5,54 log
      CFU/mL, S. aureus was detected at levels from 3,24 to 4,94 log CFU/mL, and the
      total coliform counts ranged from 4,48 to 7,18 log CFU/mL. The number of E. coli
      specimens ranged from 2,96 to 5,75 log CFU/mL. Microbial insecurity was noted for
      commercialized curd cheese, and the need for intervention was indicated.

PMID- 29362564
TI  - Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A
      Retrospective Single-Centered Analysis.
AB  - Immune thrombocytopenia (ITP) in children has a varied course and according to
      duration is distinguished as newly diagnosed (<3 months), persistent (3-12), and
      chronic (>12) types. Several studies have evaluated the prognostic factors for
      the progression of the disease, but similar works have yet to be performed in
      Greece. We aimed to identify prognostic markers for the three forms of the
      disease in 57 Greek children during a 13-year period. Information regarding age,
      gender, preceding infection, bleeding type, duration of symptoms and platelets at
      diagnosis, treatment, disease course, and immunological markers was recorded. 39
      children had newly diagnosed, 4 persistent, and 14 chronic disease. Chronic ITP
      children were more likely to be of age > 10 years (p = 0.015) and have gradual
      initiation of the disease (p = 0.001), platelets > 10 * 109/L (p = 0.01), and
      impaired immunological markers (p < 0.003) compared to newly diagnosed/persistent
      groups. Recent history of infection was found mainly in the newly
      diagnosed/persistent group (p = 0.013). None of the children exhibited severe
      spontaneous bleeding. Conclusion. Even though ITP in children usually has a self
      limited course, with rare serious bleeding complications, the chronic form of the
      disease is characterized by different predictive parameters, which can be used in
      clinical practice.

PMID- 29362566
TI  - Occipitocervical Hemolymphangioma in an Adult with Neck Pain and Stiffness: Case
      Report and Literature Review.
AB  - Introduction: Hemolymphangioma is an extremely rare malformation of the lymphatic
      and blood vessels. A limited number of hemolymphangioma cases occurring in the
      pancreas, extremities, spleen, and other organs have been reported until
      September 2017. To the best of our knowledge, no cases of hemolymphangioma in the
      occipitocervical region have been reported in the literature. Case Presentation:
      We reported the case of a 23-year-old male patient with an occipitocervical
      lesion presenting atypically as neck pain and stiffness over a period of five
      months. Although hemolymphangioma has historically demonstrated a female
      predilection (2.25 : 1 female to male) and presentation in the third to fourth
      decades of life, this case is an atypical manifestation occurring in a young male
      patient. The clinical characteristics and management choices of this uncommon
      case of hemolymphangioma in the occipitocervical region are discussed, and a
      review based on the available literature is also presented. Conclusion:
      Hemolymphangioma of the occipitocervical region is an uncommon presentation of a
      rare lesion. Although rare, hemolymphangioma should be considered a differential
      diagnosis for masses occurring in the occipitocervical region. Complete surgical
      resection is the treatment of choice and affords a good prognosis.

PMID- 29362567
TI  - Cellular and Molecular Mechanisms of Mesenchymal Stem Cell Actions.

PMID- 29362568
TI  - The Optimal Intervention Time of Bone Marrow Mesenchymal Stem Cells in
      Ameliorating Cardiac Fibrosis Induced by Viral Myocarditis: A Randomized
      Controlled Trial in Mice.
AB  - Bone marrow-derived mesenchymal stem cells (BMSCs) have recently been introduced
      to treat cardiovascular diseases, such as myocardial infarction and dilated
      cardiomyopathy. Nevertheless, there are few researches focused on the application
      of BMSCs in treating viral myocarditis, not to mention its optimal intervention
      timer potential mechanisms. In our study, we concentrated on finding an optimal
      time window to perform BMSCs treatment in a murine model of myocarditis induced
      by coxsackievirus B3 (CVB3). On the 1st day, 3rd day, 7th day, and 14th day after
      BALB/c mice were infected by CVB3, we intravenously injected equivalent BMSCs
      into the treatment groups. With a 28-day follow-up after inoculation, we found
      that the ventricular function was significantly improved in the BMSCs treatment
      group and cardiac fibrosis markedly ameliorated, especially when BMSCs were
      injected between 1 and 2 weeks after CVB3 inoculation. Furthermore, we
      demonstrated that after BMSCs treatment, the expressions of TGF-beta, col1alpha1,
      and col3alpha1 were significantly decreased. Therefore, we conclude that BMSCs
      may have a potential to improve CVB3-induced myocarditis by ameliorating cardiac
      fibrosis through the inhibition of TGF-beta expression.

PMID- 29362569
TI  - Patient-prosthesis mismatch in patients treated with transcatheter aortic valve
      implantation - predictors, incidence and impact on clinical efficacy. A
      preliminary study.
AB  - Introduction: Patient-prosthesis mismatch (PPM) is relatively frequent after
      surgical aortic valve replacement (SAVR) and negatively impacts prognosis. Aim:
      We sought to determine the frequency and clinical effects of PPM after
      transcatheter aortic valve implantation (TAVI). Material and methods: Overall,
      238 patients who underwent TAVI were screened. Moderate PPM was defined as
      indexed effective orifice area (EOAi) between 0.65 and 0.85 cm2/m2, and severe
      PPM as < 0.65 cm2/m2. All-cause mortality and the Valve Academic Research
      Consortium 2 (VARC-2) defined composite of clinical efficacy at 1 year were the
      primary endpoints. Results: Finally, 201 patients were included (mean age: 79.6
      +/-7.4 years, 52% females). The femoral artery served as the delivery route in
      79% and most of the prostheses were self-expanding (68%). Any PPM was present in
      48 (24%) subjects, and only 7 (3.5%) had severe PPM. Body surface area (BSA)
      independently predicted any PPM (OR = 16.9, p < 0.001) whereas post-dilation
      tended to protect against PPM (OR = 0.46, p = 0.09). All-cause mortality was
      similar in patients with moderate or severe PPM as compared to those with no PPM
      (14.6% vs. 14.3% vs. 13.1%, respectively, log-rank p = 0.98). Neither moderate
      (OR = 1.6, 95% CI: 0.8-3.2, p = 0.16) nor severe PPM (OR = 1.67, 95% CI: 0.36
      7.7, p = 0.51) had a significant impact on composite endpoint, or its elements,
      with the exception of transvalvular pressure gradient > 20 mm Hg. Conclusions:
      Severe PPM after TAVI is rare, can be predicted by larger BSA and does not seem
      to affect mid-term mortality or composite clinical outcome. Larger studies are
      needed to find different independent predictors of PPM and elucidate its impact
      in terms of device durability and long-term clinical efficacy.

PMID- 29362570
TI  - Left ventricular remodelling pattern and its relation to clinical outcomes in
      patients with severe aortic stenosis treated with transcatheter aortic valve
      implantation.
AB  - Introduction: Left ventricular hypertrophy (LVH) is a common compensating process
      in the pressure overload mechanism of aortic stenosis (AS). Aim: To identify a
      group of patients with a LVH pattern which may alter periprocedural and 1-year
      outcomes after transcatheter aortic valve implantation (TAVI). Material and
      methods: Echocardiographic examinations of 226 patients with severe AS treated
      with TAVI between March 2010 and February 2016 were retrospectively analysed and
      correlated with echocardiographic parameters and clinical outcomes in the study
      group. Ultimately 208 patients were enrolled in the study. Based on left
      ventricular mass index (LVMI) and relative wall thickness (RWT) patients were
      divided into three categories: concentric remodelling (CR), concentric
      hypertrophy (CH) and eccentric hypertrophy (EH). Most of the patients with severe
      AS referred for TAVI were found to have CH (n = 150, 72.8%), then EH (n = 33,
      16%) and CR (n = 16, 7.8%). Results: There were no significant differences
      between groups in terms of periprocedural outcomes or complications. After a mean
      observation time of 561.8 +/-239.0 days, the observed all-cause mortality rate
      was 19.9%. After multivariable adjustment, CR remained associated with a higher
      risk of mortality (HR = 4.31; 95% CI: 1.607-11.538; p = 0.004). Conclusions: Left
      ventricular hypertrophy is common in patients with severe AS prior to TAVI. The
      LVH pattern does not affect TAVI-related complications. In patients with severe
      AS referred for TAVI, CR seems to be the least favourable geometry of LVH,
      increasing the risk of 1-year all-cause death.

PMID- 29362572
TI  - Native aortic coarctation stenting in patients >= 46 years old.
AB  - Introduction: Stent implantation is an effective therapy for aortic coarctation
      (CoA) in adolescents and adults. Aim: To present a unique group of patients with
      native coarctation of the aorta older than or equal to 46 years treated with bare
      metal or covered stents. Material and methods: Since 2002 we have performed stent
      implantations by applying bare metal stents or covered stents using femoral
      access in 24 patients aged 46 and older. Results: We used the Mullins technique
      in all cases, implanting different stents: Palmaz, Cheatham-Platinum (CP),
      covered CP or Andrastents XL/XXL. Twenty-one procedures were elective and 3 were
      urgent. Eighteen bare metal stents (2 stents in one patient) and 7 covered stents
      were used. All procedures were effective (CoA gradient reduced < 20 mm Hg),
      despite 2 migrations of bare metal stents. Mean gradient was reduced from 50.6 +/
      15.3 to 6.8 +/-6.5 mm Hg (p < 0.001) and mean lumen diameter of stenosed aorta
      increased from 5.5 +/-2.5 to 14.9 +/-5.2 mm (p < 0.001). One special case is
      discussed - a 49-year-old man with end staged heart failure and severe CoA, who
      underwent a rescue procedure with a bare metal stent. One serious complication -
      stroke of the central nervous system - was observed in a 53-year-old woman during
      covered stent implantation (symptoms resolved during rehabilitation process).
      Conclusions: Stent implantation of native coarctation of the aorta is also a safe
      procedure in the eldest patients and is associated with persistent relief of
      aortic obstruction.

PMID- 29362571
TI  - Right heart catheterization procedures in patients with suspicion of pulmonary
      hypertension - experiences of a tertiary center.
AB  - Introduction: Right heart catheterization (RHC) is an invasive procedure
      providing direct and accurate measurements of hemodynamics of the cardiovascular
      system. Acute pulmonary vasoreactivity testing (APVT) following basal RHC in some
      patients is an established tool evaluating the reversibility of hypertension in
      the pulmonary vasculature. Aim: We sought to assess the most common indications,
      vascular approaches and complications during RHC in a single high-volume center.
      Material and methods: A total of 534 RHC procedures in 348 patients (64% male)
      were performed. The prospective registry was carried out for 28 months. Collected
      data included indications for RHC, vascular approaches, hemodynamic and clinical
      data, complications and response of pulmonary vessels in APVT. Results: In 401
      (75%) procedures pulmonary hypertension (mean pulmonary artery pressure (mPAP) >=
      25 mm Hg) was confirmed. Left heart failure was the most common indication
      (55.8%), mainly ischemic (26%) or dilated cardiomyopathy (19.9%). Other
      indications included a suspicion of arterial (21.7%), or chronic thromboembolic
      pulmonary hypertension (14.6%). The right internal jugular vein approach was used
      in 89.1% of procedures. Acute pulmonary vasoreactivity testing was performed in
      143 patients, and it was positive in 67 (46.9%) cases. Complications occurred in
      21 (3.9%) procedures and included pulmonary edema (0.2%), pneumothorax (0.2%) and
      puncture of the artery followed by the insertion of a vascular sheath (0.4%),
      atrial arrhythmia (0.2%), superior vena cava dissection (0.2%), incidental artery
      puncture (1.1%) and local hematoma (2.2%). Conclusions: The most frequent
      indication for RHC was left heart failure, and the most common approach was the
      right internal jugular vein. RHC is safe procedure with a low rate of major
      complications.

PMID- 29362573
TI  - Closure of mitral paravalvular defects without performing an arteriovenous loop:
      a case series of fourteen patients.
AB  - Introduction: The arteriovenous (AV) loop is recommended when further support is
      needed during paravalvular leak (PVL) closure. Aim: We report the feasibility and
      safety of mitral PVL closure without constructing an AV loop, based on a single
      centre experience. Material and methods: Fourteen patients with mitral valve
      replacement (MVR) who had New York Heart Association (NYHA) class III-IV dyspnoea
      or NYHA class II symptoms with significant haemolytic anaemia caused by severe or
      moderate-to-severe paravalvular regurgitation and who underwent transcatheter PVL
      closure (TPVLC) between May 2014 and February 2017 were enrolled. Results: In
      total, 15 PVL procedures and 19 device deployments were performed. The patients
      had one (n = 10), three (n = 1) or four (n = 1) devices for closure at the time
      of the procedure; one patient had two devices from two procedures at different
      times with different access ways. Nineteen devices (10 (66.6%) via transseptal
      access; 4 (26.6%), transapical access; and 1 (6.6%), retrograde access) were
      deployed successfully without making an AV loop. Conclusions: The TPVLC is a less
      invasive and effective alternative to surgery in symptomatic patients with
      significant PVLs and high operational risks. The success rates are satisfactory,
      with improving techniques and devices. Procedural success without using an AV
      loop can be achieved with reduced costs, fluoroscopic times and complications.

PMID- 29362574
TI  - Emergency abdominal surgery in patients with left ventricular assist device:
      short- and long-term results.
AB  - Introduction: Emergency abdominal surgery (EAS) in patients with long-term
      mechanical circulatory support and strong anticoagulation is very difficult. Aim:
      To present our experiences regarding the short- and long-term results of patients
      with a left ventricular assist device (LVAD) who underwent emergency abdominal
      surgery under general anesthesia at a large tertiary healthcare center. Material
      and methods: The electronic medical records of 7 patients with LVAD who underwent
      EAS between January 1, 2010 and December 31, 2016 were retrospectively
      investigated in order to evaluate perioperative management and outcomes. The
      patients were divided into two groups based on the need for EAS procedures.
      Results: Seven (9.2%) of 76 patients with LVAD underwent EAS an average of 79.1
      +/-79.4 days after implantation. No statistically significant differences were
      found between the groups with and without EAS with regard to demographic
      characteristics, type of device, and rate of perioperative mortality (p > 0.05).
      The indications for surgery, retroperitoneal hematoma in 2 patients and in 5
      other patients; ileus, iatrogenic splenic injury associated with thoracentesis,
      splenic abscess, acute abdominal pain and rectal cancer surgery was a pelvic
      abscess in a patient who is connected to the stump. In all cases laparotomy was
      performed with median incision. The perioperative mortality rate was 28.6% (n =
      2). Two patients underwent orthotopic heart transplant during long-term follow
      up. Conclusions: The EAS is not rare during LVAD treatment but is a rather
      complex procedure. General surgeons will be increasingly likely to encounter such
      patients as their numbers rise and their life expectancies are prolonged.

PMID- 29362575
TI  - Minimally invasive coronary artery bypass as a safe method of surgical
      revascularization. The step towards hybrid procedures.
AB  - Introduction: Coronary artery disease is nowadays responsible for approximately
      15% of hospitalizations in Poland. Minimally invasive coronary artery bypass
      (MIDCAB) represents an attractive alternative to a sternotomy, and at the same
      time provides better life quality and facilitates quick rehabilitation. Aim: To
      evaluate whether MIDCAB can be performed with similar early and mid-term results
      as off-pump coronary artery bypass (OPCAB) and therefore can be considered as a
      safe stage in hybrid revascularization. Material and methods: In a retrospective
      cohort study, we analyzed 73 consecutive patients who underwent coronary artery
      bypass grafting (left internal mammary artery to left anterior descending artery)
      between 2013 and 2016 in the Department of Cardiovascular Surgery and
      Transplantology, John Paul II Hospital, Krakow. Thirty-eight (52.1%) MIDCAB and
      35 (47.9%) OPCAB patients were enrolled. Results: Short-term results did not
      significantly differ between groups and similar 30-day mortality was observed
      (MIDCAB 2.6% vs. OPCAB 2.9%, p = 1). The median follow-up period was 21 months.
      There were no statistical differences in terms of overall survival or cardiac
      mortality between groups (94.7% vs. 88.6%, p = 0.42; 2.6% vs. 2.9%, p = 1,
      respectively). The rate of hospitalization due to cardiac causes was similar in
      both groups (7.9% vs. 5.1%, p = 1) and there were no differences in current
      exacerbation of angina or heart failure, with median NYHA class I and CCS class I
      in both groups. Conclusions: Despite higher technical difficulty, MIDCAB
      procedures can be performed with similar safety results as OPCAB procedures. No
      differences in terms of mortality, repeat revascularization or recurrent angina
      are observed.

PMID- 29362576
TI  - No-reflow and platelet reactivity in diabetic patients with ST-segment elevation
      myocardial infarction: is there a link?

PMID- 29362577
TI  - Comparison of demographics, cardiovascular risk factors profile and prevalence of
      coexistent atherosclerotic vascular disease in patients with severe aortic
      stenosis stratified according to dichotomized stenosis severity.

PMID- 29362578
TI  - Late complications of transcatheter atrial septal defect closure requiring urgent
      surgery.

PMID- 29362579
TI  - Right coronary artery stenosis unmasking ischemia in a patient with bilateral
      coronary pulmonary fistulas.

PMID- 29362580
TI  - Right atrium tumor - pseudoaneurysm of right coronary artery. A rare complication
      after percutaneous coronary intervention.

PMID- 29362581
TI  - Contrast-enhanced computed tomography for early detection of acute myocardial
      infarction due to blunt chest trauma.

PMID- 29362582
TI  - Transcatheter transapical valve-in-valve implantation for degenerated mitral
      bioprosthesis.

PMID- 29362583
TI  - Percutaneous mitral balloon valvuloplasty. Difficult mitral valve crossing.

PMID- 29362585
TI  - 18th Interventional Cardiology Workshop New Frontiers in Interventional
      Cardiology: December 7th, 2017, Krakow, Poland.

PMID- 29362584
TI  - Acute embolisation of Watchman plug onto aortic bioprosthesis followed by
      successful percutaneous removal.

PMID- 29362586
TI  - Hypericum perforatum: Synthesis of Active Principles during Flowering and
      Fruitification-Novel Aspects of Biological Potential.
AB  - St. John's wort is a widely used medicinal plant. The quality of herbal drug,
      which is in most of the cases collected from nature, varies. Therefore, the aim
      of the present study was detailed chemical characterization of Hypericum
      perforatum subsp. perforatum samples collected in close time intervals during
      flowering and fruitification with the purpose to state the phenological stage
      characterized by maximum levels of active principles. The antioxidant potential
      and potential to inhibit biologically important enzymes, as well as the
      cytotoxicity and genotoxicity of the sample collected during the full flowering
      period, were evaluated. Data showed that the optimal period for the achieving of
      maximum level of active principles is the phenophase between floral budding and
      flowering stage. Significant antioxidant potential and the ability to inhibit
      biologically important enzymes (especially alpha-glucosidase) were recorded. The
      extract exhibited no genotoxicity in subcytotoxic concentrations, while increased
      cytotoxicity recorded in cotreatment with bleomycin on malignant cell lines was
      especially significant.

PMID- 29362587
TI  - Medicinal Herbs and Their Active Compounds for Fatty Liver Diseases.

PMID- 29362588
TI  - Tang-Luo-Ning, a Traditional Chinese Medicine, Inhibits Endoplasmic Reticulum
      Stress-Induced Apoptosis of Schwann Cells under High Glucose Environment.
AB  - Tang-Luo-Ning (TLN) has a definite effect in the clinical treatment of diabetic
      peripheral neuropathy (DPN). Schwann cells (SCs) apoptosis induced by endoplasmic
      reticulum stress (ER stress) is one of the main pathogeneses of DPN. This study
      investigates whether TLN can inhibit SCs apoptosis by inhibiting ER stress
      induced apoptosis. Our previous researches have demonstrated that TLN could
      increase the expression of ER stress marker protein GRP78 and inhibited the
      expression of apoptosis marker protein CHOP in ER stress. In this study, the
      results showed that TLN attenuated apoptosis by decreasing Ca2+ level in SCs and
      maintaining ER morphology. TLN could decrease downstream proteins of CHOP
      including GADD34 and Ero1alpha, while it increased P-eIF2alpha and decreased the
      upstream proteins of CHOP including P-IRE1alpha/IRE1alpha and XBP-1, thereby
      reducing ER stress-induced apoptosis.

PMID- 29362589
TI  - Antinociceptive Activities of the Methanolic Extract of the Stem Bark of
      Boswellia dalzielii Hutch. (Burseraceae) in Rats Are NO/cGMP/ATP-Sensitive-K+
      Channel Activation Dependent.
AB  - Boswellia dalzielii (B. dalzielii) is traditionally used in the treatment of
      rheumatism, pain, and inflammation. The present investigation evaluates the
      property and possible mechanism of action of the methanolic extract of B.
      dalzielii (BDME) on inflammatory and neuropathic pain models. Effects of BDME
      (250 and 500 mg/kg), orally administered, were verified in mechanical
      hypernociception induced by LPS or PGE2. Mechanical hyperalgesia, cold allodynia,
      and heat hyperalgesia were used in vincristine-induced neuropathic pain. NW-nitro
      L-arginine methyl ester (inhibitor of nitric oxide synthase), glibenclamide (ATP
      sensitive potassium channel blocker), methylene blue (cGMP blocker), or naloxone
      (opioid antagonist receptor) has been used to evaluate the therapeutic effects of
      BDME on PGE2-induced hyperalgesia. Chemical profile of BDME was determined by
      using HPLC-XESI-PDA/MS. BDME showed significant antinociceptive effects in
      inflammatory pain caused by LPS and PGE2. The extract also significantly
      inhibited neuropathic pain induced by vincristine. The antinociceptive property
      of BDME in PGE2 model was significantly blocked by L-NAME, glibenclamide,
      methylene blue, or naloxone. The present work reveals the antinociceptive
      activities of BDME both in inflammatory and in neuropathic models of pain. This
      plant extract may be acting firstly by binding to opioid receptors and secondly
      by activating the NO/cGMP/ATP-sensitive-K+ channel pathway.

PMID- 29362590
TI  - Larvicidal Activity against Aedes aegypti and Chemical Characterization of the
      Inflorescences of Tagetes patula.
AB  - The crude acetone extract (CAE) of defatted inflorescences of Tagetes patula was
      partitioned into five semipurified fractions: n-hexane (HF), dichloromethane
      (DF), ethyl acetate (EAF), n-butanol (BF), and aqueous (AQF). BF was fractionated
      by reversed-phase polyamide column chromatography, obtaining 34 subfractions,
      which were subjected to HSCCC, where patuletin and patulitrin were isolated. CAE
      and the fractions BF, EAF, DF, and AQF were analyzed by LC-DAD-MS, and patuletin
      and patulitrin were determined as the major substances in EAF and BF,
      respectively. BF was also analyzed by HPLC and capillary electrophoresis (CE),
      and patulitrin was again determined to be the main substance in this fraction.
      CAE and the semipurified fractions (750, 500, 300, 100, and 50 mg/L) were assayed
      for larvicidal activity against Aedes aegypti, with mortality rate expressed as
      percentage. All fractions except AQF showed insecticidal activity after 24 h
      exposure of larvae to the highest concentration. However, EAF showed the highest
      activity with more than 50% reduction in larval population at 50 mg/L. The
      insecticidal activity observed with EAF might have been due to the higher
      concentration of patuletin present in this fraction.

PMID- 29362591
TI  - Influence of Institution-Based Factors on Preoperative Blood Testing Prior to Low
      Risk Surgery: A Bayesian Generalized Linear Mixed Approach.
AB  - To optimize delivery of health care services in clinical practice, the use of
      unnecessary interventions should be reduced. Although recommendations for this
      reduction have been accepted worldwide, recent studies have revealed that the use
      of such procedures continues to increase. We conducted a retrospective cohort
      study using a nationwide claim-based database to evaluate factors influencing
      preoperative blood testing prior to low-risk surgery, via a Bayesian generalized
      linear mixed approach. The study period was set from April 1, 2012, to March 31,
      2016, and 69,252 surgeries performed at 9,922 institutions were included in the
      analysis. Mean patient age was 44.3 +/- 11.3 years (57% female). Preoperative
      blood tests were performed for 59.0% of procedures. Among institutional factors,
      the number of beds was strongly associated with preoperative blood testing (odds
      ratio [95% highest posterior density interval (HPD interval)], 2.64 [2.53 to
      2.75]). The difference (95% credible interval) in the rate of preoperative blood
      testing between institutions with <100 beds and >=100 beds was 0.315 [0.309 to
      0.322], and the Bayesian index theta was 1.00. This indicated that preoperative
      blood tests are strongly influenced by institutional factors, suggesting that
      specific guidelines should be developed to avoid excessive preoperative testing
      for low-risk surgery.

PMID- 29362592
TI  - Mathematical Modeling and Control of Infectious Diseases.

PMID- 29362593
TI  - Editorial.

PMID- 29362594
TI  - Overview of IgG4 - Related Disease.
AB  - : Rationale (hypothesis): IgG4-related disease (IgG4-RD) is a pathological entity
      recently recognized by the medical world that can affect any organ or system.
      However, there is insufficient data about this disease in medical literature. Aim
      (objective): A more extensive clarification of the IgG4 molecule, the diversified
      aspects of IgG4-related disease, and the response of this disease to treatment,
      will provide a crucial understanding of the immune system and other diseases now
      known to be associated with IgG4. METHODS AND RESULTS: The MEDLINE online medical
      database was used, and, after a comprehensive review of medical articles
      regarding IgG4-RD, published after 2003, using the search words "IgG4- related
      disease" and "IgG4 molecule", we have described the clinical, pathological and
      therapeutic features of IgG4-RD, as well as the presence of the IgG4 molecule in
      the evolution, diagnosis and management of this syndrome. We characterized the
      potential disease mechanisms and discussed early observations related to
      treatment. DISCUSSION: Given the response to immunosuppressive therapy, it is
      hypothesized that IgG4-related disease is most likely an autoimmune disease.
      Therefore, IgG4-related disease is a fibro-inflammatory condition that can affect
      any organ and can lead to the formation of pseudotumoral lesions requiring
      differential diagnosis with various malignancies. Positive diagnostic criteria
      are histopathological and require at least two features out of the following
      three: dense limphoplasmocitary infiltrate, storiform fibrosis, obliterative
      phlebitis.

PMID- 29362595
TI  - Protocol for a Systematic Review and Meta-Analysis of Lithium, Anticonvulsive or
      atypical antipsychotic Drugs for Treatment of Refractory Obsessive-Compulsive
      Disorder.
AB  - INTRODUCTION: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder
      that causes significant distress to the afflicted individual. About half of OCD
      patients treated with an adequate trial of serotonin reuptake inhibitors fail to
      fully respond to treatment and continue to exhibit significant symptoms.
      Therefore, there is a need for other agents to alleviate the symptoms of these
      disorders. In spite of considerable research including numerous randomized
      controlled trials and systematic reviews, there exists uncertainty regarding what
      treatments are effective. In this systematic review, we evaluated the efficacy of
      mood stabilizers in treatment-refractory OCD. MATERIALS AND METHODS: We conducted
      a meta-analysis of all randomized clinical trials evaluating lithium,
      anticonvulsive agents or atypical antipsychotic drugs for OCD to determine which
      therapies show more effective than a placebo, in reducing obsessive-compulsive
      symptoms. We acquired eligible studies through a systematic search of Cochrane
      Central Registry of Controlled Trials, MEDLINE, EMBASE, PsycINFO, Scopus,
      ProQuest and Google scholar. We conducted meta-analyses to establish the effect
      of lithium, anticonvulsive agents, or atypical antipsychotic drugs on patient
      important outcomes when possible. To assess relative effects of treatments, we
      constructed a random effect model. DISCUSSIONS: Our review was the first to
      evaluate all treatments for OCD, to provide the relative effectiveness of
      lithium, anticonvulsive agents, or atypical antipsychotic drugs, and prioritize
      patient-important outcomes with a focus on functional gains. Our review
      facilitated the evidence-based management of patients with resistant OCD, and
      identified the key areas for future research.

PMID- 29362596
TI  - Cerebrolysin and early neurorehabilitation in patients with acute ischemic
      stroke: a prospective, randomized, placebo-controlled clinical study.
AB  - Background - Stroke represents one of the most important causes of permanent
      physical or mental disability. A number of recent advances in recovery have
      reinforced the idea that pharmacological intervention combined with a specific
      rehabilitation therapy can reduce disability after stroke. Objective - The aim of
      this trial was to demonstrate the hypothesis that the association of
      pharmacological treatment with Cerebrolysin to early physical therapy can
      significantly stimulate the endogenous processes underlying the recovery after an
      ischemic stroke. Methods and Results - It was a prospective, randomized, double
      blind, placebo-controlled clinical study. 60 patients were randomized either to
      30 ml/ day Cerebrolysin or to Placebo for 10 consecutive days, starting in the
      first 24-48 hours after stroke. The pharmacological treatment was paired with
      early physical rehabilitation. The robust nonparametric evaluation of the
      National Institute for Health Stroke Scale (NIHSS) demonstrated a large
      superiority of Cerebrolysin relative to placebo on day 10 with a MW=0.79 (95% CI,
      0.65-0.94), respectively on day 30 with MW=0.75 (95% CI, 0.60-0.89). Similar
      results were found with modified Ranking Scale (mRS) and Barthel Index (BI).
      Cerebrolysin was safe and well tolerated. Conclusions - Cerebrolysin had a
      beneficial effect on global neurological status and disability. The beneficial
      results of this study can be easily applied in the current clinical practice.
      Abbreviations: BI = Barthel Index; CB = Changes from Baseline; CI = Confidence
      interval; ICH = International Conference on Harmonization; ITT = intention-to
      treat; LB = Lower Bound of Confidence Interval; mRS = modified Rankin Scale; MW =
      Mann-Whitney; NIHSS = National Institute for Health Stroke Scale; P = P-value; R
      = Valid Number Reference Group (Placebo); SD = standard deviation; T = Valid
      Number Test Group (Cerebrolysin); UB = Upper Bound of Confidence Interval.

PMID- 29362597
TI  - Health-related quality of life of rheumatic disease patients treated in a
      specialized IPS in Medellin, Colombia.
AB  - PURPOSE: To compare Health-Related Quality of Life (HRQOL) profiles and their
      associated factors in people with rheumatoid arthritis (RA), spondyloarthritis
      (SpA), fibromyalgia (FM) and rheumatoid comorbidity treated in a specialized
      health center (SHC) in Medellin, Colombia. METHODS: A cross-sectional analytical
      study was performed with 93 RA patients, 30 SpA patients, 41 primary FM patients
      and 48 secondary FM patients with a concurrent diagnosis of RA or SpA. A
      demographic, socioeconomic, and clinical survey (the IPAQ, International Physical
      Activity Questionnaire) and the SF-36 survey validated in Medellin were
      administered. The statistical analyses were executed using SPSS 21.0 Results.
      Significant differences were found in all HRQOL dimensions among the patients,
      with physical performance perceived as the worst in the four groups. FM had the
      worst HRQOL profile, whereas the least affected group was SpA. Patients with RA
      and rheumatoid comorbidity shared similar HRQOL scores. The years of study, age
      and economic satisfaction variables were associated with the physical
      performance, vitality, social functioning, and mental health domains. CONCLUSION:
      The HRQOL profile was negative in patients with rheumatic diseases and lower in
      patients with FM. Additionally, variables or subgroups with greater deterioration
      were identified. This information will be useful for health activities and
      generate evidence in favor of incorporating HRQOL measurements into rheumatology
      services to complement clinical evaluations.

PMID- 29362598
TI  - Correlation between the wide range of tubal pathology discovered by routine
      hysterosalpingography in a university hospital in Romania and the successful
      pregnancy rate. A cohort study.
AB  - RATIONALE: Hysterosalpingography is still the main method to begin with when
      studying the causes of female impossibility to conceive a baby. OBJECTIVE: The
      aim of this study is to correlate and evaluate the wide range of tubal pathology
      discovered by routine hysterosalpingography in a university hospital in Romania
      with the successful pregnancy rate. METHODS AND RESULTS: A total of 95
      consecutive patients explored by routine hysterosalpingography in a university
      hospital during 2015 and 2016 were included. Out of 173 fallopian tubes studied,
      28.9% were occluded, 13.29% were almost occluded, and only 57.8% were patent. Of
      these patients, 11 successful pregnancies occurred in 95 women (11.57%) until
      September 2017. A number of 7 patients delivered a normal baby in our hospital
      (7.36%). One patient was admitted at 36 weeks of gestation, and another one at 26
      weeks of gestation, for risk of premature delivery. None of these two patients
      delivered in our hospital. Two patients were admitted for miscarriage at 8 weeks
      and 5 weeks of pregnancy. In all the 7 patients who delivered a normal baby, the
      fallopian tubes were entirely visible (100%), whether they were patent or not.
      DISCUSSION: To our knowledge, this is the largest study about
      hysterosalpingography and the successful pregnancy rate in Romania so far.
      ABBREVIATIONS: ART= Assisted reproductive technologies.

PMID- 29362599
TI  - Effect of Dialyzable Leukocyte Extract on chronic cervicitis in patients with HPV
      infection.
AB  - : The objective of the study was to assess the clinical, histopathological and
      immunochemical changes induced by dialyzable leukocyte extract (DLE) treatment in
      patients with chronic cervicitis associated to HPV infection. Fifty-four female
      Mexican patients diagnosed with chronic cervicitis, cervical intra-epithelial
      neoplasia grade 1 (CIN 1) and HPV infection were divided into two groups:
      patients treated with placebo and patients treated with DLE. Clinical and
      colposcopy evaluations were performed before and after treatments. Cervix
      biopsies were obtained to analyze histopathological features and to determine the
      local immunological changes by immunohistochemistry analyses. Placebo-treated
      patients showed no significant changes in the evaluated parameters.
      Interestingly, in DLE-treated patients, clinical manifestations of cervicitis
      diminished and 89% of them remitted the colposcopic lesions. Histological
      analyses of biopsies from DLE-treated patients showed a decreasing leukocyte
      infiltrate. Immunochemical analyses showed an increased expression of TGF-beta,
      while expression of IFN-gamma, PCNA, and IL-32 decreased. Our results suggest
      that DLE can stimulate innate immunity of cervical mucosae, diminishing chronic
      cervicitis in HPV-infected patients. TRIAL REGISTRATION: Register ISRCTN16429164
      Abbreviations: HPV = Human Papilloma Virus; DLE = Dialyzable leukocyte extract.

PMID- 29362600
TI  - Palmitate-induced insulin resistance is attenuated by Pioglitazone and EGCG
      through reducing the gluconeogenic key enzymes expression in HepG2 cells.
AB  - HYPOTHESIS: Palmitate causes insulin resistance (IR) in insulin target tissue.
      Pioglitazone (an anti-hyperglycemic agent) and epigallocatechin gallate (EGCG, a
      dietary supplement) can be used for the treatment of type 2 diabetes. However,
      their molecular effects on gluconeogenesis remain unclear. OBJECTIVE: Hence, we
      aimed to investigate the simultaneous effect of these anti-hyperglycemic agents
      on gluconeogenesis through in vitro experiments. METHODS: HepG2 cells were
      treated with 0.5 mM palmitate, 10 MUM pioglitazone, and 40 MUM epigallocatechin
      gallate (EGCG). Gene expression assay was used to investigate the underlying
      mechanism. Glucose production assay was applied in culture medium to evaluate the
      activity of gluconeogenesis pathway. RESULTS: Palmitate induced IR could
      significantly increase G6Pase and PEPCK gene expressions by 58 and 30%,
      respectively, compared to the control. EGCG reduced the expression of PEPCK and
      G6Pase by 53 and 67%, respectively. Pioglitazone reduced the mRNA level of PEPCK
      and G6Pase by 58 and 62% respectively. Combined treatment of insulin-resistant
      cells with EGCG and pioglitazone significantly decreased the mRNA level of PEPCK
      and G6Pase by 73 and 80%, respectively. Treatment with palmitate increased
      glucose production by 50% in HepG2 cells. When the insulin resistant HepG2 cells
      were treated alone with EGCG and pioglitazone, the glucose production reduced by
      50 and 55%, respectively. The combined treatment with EGCG and pioglitazone
      resulted in 69% reduction in glucose production compared to the palmitate treated
      HepG2 cells. CONCLUSIONS: These data suggest the additive inhibitory effect of co
      treatment with pioglitazone and EGCG on the gluconeogenesis pathway in palmitate
      induced insulin resistance HepG2 cells.

PMID- 29362601
TI  - Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective
      study.
AB  - OBJECTIVE: To investigate the association between pernicious anemia and other
      autoimmune diseases. METHODS: This retrospective and bicentric study was
      conducted at Reims and Strasbourg University Hospitals and involved 188 patients
      with pernicious anemia examined between 2000 and 2010 in order to search for
      other autoimmune diseases and to evaluate the role of pernicious anemia in
      autoimmune polyglandular syndrome. RESULTS: A total of 74 patients with a
      combination of pernicious anemia and other autoimmune diseases were included in
      the study. Our study revealed the privileged association of pernicious anemia
      with autoimmune thyroiditis. The association of pernicious anemia and autoimmune
      thyroiditis are a part of the autoimmune polyglandular syndrome type 3b.
      CONCLUSION: We suggest undertaking a systematic clinical examination and
      laboratory investigations in search of autoimmune thyroiditis in patient(s) with
      the diagnosis of pernicious anemia. The association of pernicious anemia and
      autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.

PMID- 29362602
TI  - Histological Characteristics of Bruises with Different Age.
AB  - BACKGROUND: In forensics bruises as injuries take an important part in the
      interpretation of the causes of death. Since activating the inflammatory response
      of the body in their formation, histological analysis of the bruised tissue can
      provide data on the determination the time when the injury occurred. AIM: The aim
      of this study is to compare the histological features of 1-day and 5-days old
      bruises. MATERIAL AND METHODS: Bruised human skin samples, 1-day old in group A
      and 5-day-old in group B, obtained at autopsy from individuals who died from a
      violent death, were analyzed in this study. The qualitative microscopic analysis
      was performed on serial paraffin sections of tissues stained with Hematoxylin
      eosin and Pearls Prussian Blue method, using a light microscope connected to a
      digital camera. RESULTS: Qualitative histological analysis of the studied group A
      presented with fresh bruises, less than 24 hours old, showed ruptured smaller
      vessels and extravasated red blood cells in the connective tissue of the skin,
      with subsequent expansion and infiltration of fibrous septa of the skin. In the
      area of bleeding an initial infiltration by macrophages was observed. In the
      studied group B, presented with bruises 3-7 days old, histological analysis
      showed a marked presence of hemosiderin-laden macrophages and presence of
      hematoidin granules in the area of bleeding, as well as ruptured small blood
      vessels and red blood cells extravasation in the dilated fibrous septa.
      CONCLUSION: A detailed analysis of tissue changes in bruises every day from the
      initiation until their recovery, a detailed description of the histological
      finding can be given, which will be supported in the precise determination of the
      age of the injuries themselves.

PMID- 29362603
TI  - The Palm-Heart Diameter: A Prospective Simple Screening Tool for Identifying
      Heart Enlargement.
AB  - BACKGROUND: Several speculations have linked the size of the fist to be equal to
      the size of the heart. However, the substantial scientific report still lacks to
      support this theory. AIM: This study aims to provide the validity of the fist
      heart assumption by correlating the palm and heart diameters while benchmarking
      it as a reference tool for determining the normal heart size. MATERIALS AND
      METHOD: Volunteers from the public were recruited during a health fair organised
      by the school. A self-administered questionnaire for necessary information was
      distributed after the volunteers signed the consent forms. The palm of both hands
      was measured in duplicates using a flexible ruler. Ultrasound examination was
      used in measuring the diameter of the heart with the landmark being from the
      anterior fibrous pericardium to the lowest part of the posterior fibrous
      pericardium. The level of significance was kept at P < 0.05. RESULTS: A total of
      275 people, consisting of 123 males and 152 females participated in the study.
      The age range was from 15 to 80 years with a mean age of 28.16 +/- 16.18. The
      measurement showed that the size of both palms correlated with the heart
      diameter, p < 0.05. Other factors such as age and height showed a substantial
      level of correlation. However, this correlation ceased with older participants.
      Palm size did not correlate among participants with previously diagnosed
      prehypertension. However, participants with previously diagnosed hypertension
      with good medication compliance maintained the correlation. CONCLUSION: This
      study establishes the correlation between the palm and heart diameters. Since the
      heart tissue and the upper limb share a similar embryonic origin, being the
      mesoderm, this study prospects the fact that heart enlargement could be
      preliminarily identified by measuring the size of the hand.

PMID- 29362604
TI  - Impact of Size of the Tumour, Persistence of Estrogen Receptors, Progesterone
      Receptors, HER2Neu Receptors and Ki67 Values on Positivity of Axillary Lymph
      Nodes in Patients with Early Breast Cancer with Clinically Negative Axillary
      Examination.
AB  - AIM: The study aimed to identify factors that influence the positivity of
      axillary lymph nodes in patients with early breast cancer and clinically negative
      axillary lymph nodes, who were subjected for modified radical mastectomy and
      axillary lymphadenectomy. MATERIAL AND METHODS: This study included 81 surgically
      treated, early breast cancer patients during the period from 08-2015 to 05-2017.
      All the cases have been analysed by standard histological analysis including
      macroscopic and microscopic examination by routine H&E staining. For
      determination of molecular receptors, immunostaining by PT LINK immunoperoxidase
      has been done for HER2neu, ER, PR, p53 and Ki67. RESULTS: Patients age ranged
      between 31-73 years, an average of 56.86 years. The mean size of a primary tumour
      in the surgically treated patient was 20.33 +/- 6.0 mm. Axillary dissection
      revealed from 5 to 32 lymph nodes, with an average of 14. Metastases have been
      found in 1 to 7 lymph nodes, with an average 0.7. Only 26 (32.1%) of the patients
      showed metastases in the axillary lymph nodes. The univariant regression analysis
      showed that the size of a tumour and presence of HER2neu receptors on cancer
      cells influence the positivity of the axillary lymph nodes. The presence of the
      estrogen receptors, progesterone receptors have no influence on the positivity
      for metastatic deposits of lymph nodes. Multivariant model and logistic
      regression analysis as significant independent factors or predictors of
      positivity of the axillary lymph nodes are influenced by the tumour size only.
      CONCLUSION: Our study showed that the metastatic involvement of the axillary
      lymph nodes is mainly influenced by the size of a tumour and presence of HER2neu
      receptors in the univariant analysis. This point to the important influence of
      positivity of the axillary lymph nodes but, in multi-variant regressive analysis
      the lymph node status correlates with the tumour size only.

PMID- 29362605
TI  - Influence of Interleukin-6 (174G/C) Gene Polymorphism on Obesity in Egyptian
      Children.
AB  - BACKGROUND: Obesity is a multi-factorial chronic disorder. A considerable number
      of studies have been performed to figure out whether there is an association
      between obesity and polymorphisms of gene IL-6 (174G/C), but the results are
      equivocal. AIM: This study aimed to find out whether the IL-6 (174G/C) gene was
      associated with the risk of developing obesity in Egyptian children. SUBJECTS AND
      METHODS: The study included 149 children and adolescents with age ranged between
      9.5 - 18 years. Eighty-five of them were obese which BMIZ-score is > 2, and sixty
      four children with BMIZ-score <= 2 served as control group. Serum level of IL-6
      and genetic analysis for IL-6 (174G/C) gene polymorphism were done. RESULTS:
      Obese children had significantly higher serum levels of IL-6 as compared to those
      of control children (P = 0.003). A high percentage of IL-6 polymorphism GC was
      found in obese subjects (93.7%), while the control group had a higher percentage
      of IL-6 polymorphism GG (70.6 %). CONCLUSION: Our study showed that carriers of
      the C allele for the IL-6 (174G/C) polymorphism have higher BMI. As the G174C
      polymorphism is likely to affect IL-6 expression and its physiological
      regulation; consequently this polymorphism may affect adiposity.

PMID- 29362607
TI  - A Comparative Study of Polymerase Chain Reaction-Restriction Fragment Length
      Polymorphism and Fungal Culture for the Evaluation of Fungal Species in Patients
      with Tinea Cruris.
AB  - BACKGROUND: Tinea cruris is the second most common dermatophytosis in the world
      and the most common in Indonesia. The conventional laboratory tests for
      dermatophyte infection are slow and less specific. Polymerase Chain Reaction
      Restriction Fragment Length Polymorphism (PCR-RFLP) is a PCR method with the
      addition of enzyme after amplification, therefore enabling for more specific
      results. AIM: This study aimed to find whether the PCR-RFLP test could yield the
      same fungal species result as a fungal culture. METHODS: The specimens were skin
      scrapings from thirty-one patients suspected tinea cruris. The tools and
      materials that were used were Sabaroud's dextrose agar media, primer ITS 1 and
      ITS 4 and MvaI. RESULTS: The equation percentage of the test result species
      between PCR-RFLP and fungal culture was 50% of 12 subjects whose the test results
      were both positive from the fungal culture and PCR-RFLP. The percentage of the
      test result with fungal culture the fungal species were found, but in the PCR
      RFLP test which the fungal species was not found, the percentage was 50% of 12
      subjects which the test results were both positive as fungi from the culture and
      PCR-RFLP test. CONCLUSIONS: The species from PCR-RFLP examination was the same
      with the fungal culture.

PMID- 29362606
TI  - Genistein Ameliorates Cyclophosphamide - Induced Hepatotoxicity by Modulation of
      Oxidative Stress and Inflammatory Mediators.
AB  - AIM: The present study investigated the protective effect of the phytoestrogen,
      genistein (GEN), against (CP)-induced acute hepatotoxicity in rats. MATERIAL AND
      METHODS: Male adult rats were randomly assigned into five groups. Normal control
      group received the vehicles; CP group received a single dose of CP (200 mg/kg,
      i.p). The other three groups received subcutaneous GEN at doses of 0.5, 1 and 2
      mg/kg/day, respectively, for 15 consecutive days prior CP injection. Sera and
      liver tissues were collected forty-eight hours after CP injection for assessment
      of liver function enzymes (ALT and AST) in rat sera, the hepatic
      oxidative/nitrosative biomarkers (GSH, MDA and NOx), hepatic interleukin-1beta,
      and myeloperoxidase activity. Immunohistochemistry of cyclooxygenase-2 and
      histopathological examination of liver tissues were also conducted. RESULTS: The
      CP-induced acute liver damage was evidenced by elevated serum ALT and AST
      accompanied by increased hepatic oxidative stress and inflammatory biomarkers.
      Immunohistochemical outcomes revealed hepatic cyclooxygenase-2 expression in CP
      group with distortion of liver architecture. GEN-pretreatment significantly
      ameliorated the deterioration of liver function and exerted significant anti
      oxidant and anti-inflammatory activity with a marked decline in hepatic
      cyclooxygenase-2 expression in a dose dependent-manner. CONCLUSION: The present
      study demonstrated that the antioxidant and anti-inflammatory activities of GEN
      might contribute to its protective effects against CP-induced liver damage.

PMID- 29362608
TI  - Rapid Identification of Aspergillus Fumigatus Using Betaeta-Tubulin and RodletA
      Genes.
AB  - AIM: The main purpose of the present study was to test the beta-tubulin and
      rodletA genes for rapid identification of Aspergillus fumigatus. MATERIALS AND
      METHODS: Fifty-one A. fumigatus strains including environmental, clinical and
      reference isolates were tested in this research. PCR was carried out based on
      betatub and rodA partial gene sequences. RESULTS: A 198 bp DNA fragment was
      obtained using betatub gene. PCR amplification of the rodA gene resulted in a 313
      bp band. The betatub and rodA genes PCR products exhibited a 100% homology with
      the associated sequences in the GenBank. CONCLUSION: In the present study, we
      used a PCR approach that was able to discriminate A. fumigatus from other related
      species within the section Fumigati.

PMID- 29362609
TI  - Hepatoprotective Effect of Camel Milk on Poloxamer 407 Induced Hyperlipidaemic
      Wistar Rats.
AB  - AIM: To investigate the effect of oral administration of camel milk on liver
      enzymes, total proteins and histology of poloxamer 407 induced hyperlipidaemic
      wistar rats. MATERIAL AND METHODS: Thirty male wistar rats weighing between 150
      200 g were randomly assigned into six groups of five each; group I: administered
      distilled water, group II: induced with P407, group III: induced with P407 and
      treated with atorvastatin (20 mg/kg) and groups IV, V and VI: induced with P407
      and treated with camel milk 250 mg/kg, 500 mg/kg and 1000 mg/kg respectively.
      After three weeks, blood samples and liver tissues were collected for the
      determination of alkaline phospatase (ALP), alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), total protein, albumin, globulin,
      albumin/globulin ratio and histological studies respectively. RESULTS: All camel
      milk treated groups showed significant (p < 0.05) decrease in ALT and AST. Camel
      milk treated groups; 250 mg/kg and 1000mg/kg showed significant (p < 0.05)
      decrease in total protein, globulin with all camel milk treated groups having
      significant (p < 0.05) increase in A/G ratio. Histological examination of liver
      tissues showed that camel milk at a dose of 250 mg/kg had slight adipocytes
      infiltration. CONCLUSION: The results of our findings highlight the
      hepatoprotective effect of camel milk in poloxamer 407 induced hyperlipidaemic
      wistar rats.

PMID- 29362610
TI  - A Comparative Study of Rat Lung Decellularization by Chemical Detergents for Lung
      Tissue Engineering.
AB  - BACKGROUND: Lung disease is the most common cause of death in the world. The last
      stage of pulmonary diseases is lung transplantation. Limitation and shortage of
      donor organs cause to appear tissue engineering field. Decellularization is a
      hope for producing intact ECM in the development of engineered organs. AIM: The
      goal of the decellularization process is to remove cellular and nuclear material
      while retaining lung three-dimensional and molecular proteins. Different
      concentration of detergents was used for finding the best approach in lung
      decellularization. MATERIAL AND METHODS: In this study, three-time approaches
      (24, 48 and 96 h) with four detergents (CHAPS, SDS, SDC and Triton X-100) were
      used for decellularizing rat lungs for maintaining of three-dimensional lung
      architecture and ECM protein composition which have significant roles in
      differentiation and migration of stem cells. This comparative study determined
      that variable decellularization approaches can cause significantly different
      effects on decellularized lungs. RESULTS: Results showed that destruction was
      increased with increasing the detergent concentration. Single detergent showed a
      significant reduction in maintaining of three-dimensional of lung and ECM
      proteins (Collagen and Elastin). But, the best methods were mixed detergents of
      SDC and CHAPS in low concentration in 48 and 96 h decellularization. CONCLUSION:
      Decellularized lung tissue can be used in the laboratory to study various aspects
      of pulmonary biology and physiology and also, these results can be used in the
      continued improvement of engineered lung tissue.

PMID- 29362611
TI  - Antigenotoxic and Antioxidant Activity of Methanol Stem Bark Extract of Napoleona
      Vogelii Hook & Planch (Lecythidaceae) In Cyclophosphamide-Induced Genotoxicity.
AB  - BACKGROUND: Napoleona vogelii is used in traditional medicine for cancer
      management. AIM: The study was conducted to evaluate the antigenotoxic and
      antioxidant activities of methanol stem bark extract of N. vogelii in male
      Sprague Dawley rats. MATERIALS AND METHOD: Thirty male Sprague Dawley rats were
      randomly divided into group 1 (control) administered 10 mL/kg distilled water,
      groups 2 and 3 were co-administered 100 mg/kg, 200 mg/kg of N. vogelli and 5
      mg/kg cyclophosphamide (CPA) respectively for 7 days p.o. Groups 4 and 5 were
      administered only 5 mg/kg CPA and 200 mg/kg NV respectively. RESULTS: The LD50
      oral was greater than 4 g/kg. There were significant (p < 0.0001) increases in
      plasma enzymatic and non-enzymatic antioxidant enzymes and significant (p <
      0.0001) decrease in percentage micronuclei in bone marrow of extract treated rats
      compared to rats administered 5 mg/kg CPA alone. There was steatosis pointing to
      cytotoxic injury in the liver of rats co-administered 200 mg/kg NV and 5 mg/kg
      CPA. Gas chromatography-mass spectrometry analysis of the extract showed the
      presence of phytol and unsaturated fatty acids. CONCLUSION: N. vogelii possesses
      antigenotoxic and antioxidant activities associated with the presence of
      phytochemicals, phytol and unsaturated fatty acids.

PMID- 29362612
TI  - Hepatitis B virus Genotypes in West Azarbayjan Province, Northwest Iran.
AB  - BACKGROUND: Infections caused by Hepatitis B are one of the world health's most
      serious problems. According to assessments, nearly 500,000 to 1.2 million people
      die each year due to chronic hepatitis, cirrhosis of the liver and hepatocellular
      carcinoma. Hepatitis B is one of the diseases which can be transferred through
      blood and its products. Clinical importance of genotypes of hepatitis B virus and
      their relations with mutations are well known. AIM: Since epidemiological data
      resulting from determining genotypes and sub-genotypes of hepatitis B can help a
      lot in defining a vaccination plan, antiretroviral therapy, detection and
      prevention of diseases, genotypes of this virus in hepatitis B patients were
      evaluated in West Azarbaijan province. MATERIALS AND METHODS: In this cross
      sectional study, serum samples of 100 hepatitis B patients (70 male/30 female)
      were taken randomly from Urmia University of Medical Sciences (UMSU) referrals,
      Urmia, Iran; and were tested positive for the presence of surface antigens of
      hepatitis B virus (HBsAg) using ELISA method. In the first method, after
      extracting the DNA of the virus, sequencing of S genes was carried out using
      Sanger method, and the sequences were aligned and edited using Bioedit software.
      In the next step, phylogenic analysis of the sequences was done in comparison
      with the reference sequences which were extracted from a gene bank, utilising
      Neighbour-joining assay method with CLUSTRAL W software. To ensure genotyping
      accuracy, the samples were tested once more, using Nested PCR method. RESULTS:
      The results were consistent with the sequence method and the dominant genotype in
      patients suffering hepatitis was type D. In other words, Iranian's HBV genotypic
      types are homogeneous and in close coordination with each other. CONCLUSIONS: The
      results reveal that D genotype is the main genotype of HBV in West Azarbayjan
      province, northwest Iran. Presence of this genotype was in conformity conformed
      withto the low rate of acute liver diseases caused by hepatitis B chronic
      infection, cirrhosis of the liver and hepatocellular carcinoma.

PMID- 29362614
TI  - Effects of Pleuran (Beta-Glucan from Pleurotus Ostreatus) Supplementation on
      Incidence and Duration of COPD Exacerbations.
AB  - BACKGROUND: 1,3/1,6-beta-glucans are recognised as immunomodulators in human and
      veterinary medicine for over 50 years. AIM: To assess the effects of pleuran
      (1,3/1,6-beta-glucan from Pleurotus ostreatus) on incidence and duration of
      bacterial exacerbations in patients with COPD. METHODS: We performed an
      observational, non-randomized, open-label study including 32 COPD patients (Group
      D) in whom besides the recommended chronic treatment for the stable disease were
      administered supplement combination containing pleuran 100 mg, vitamin C 60 mg
      and zinc 5 mg once daily over a three month-period (Group 1). Also, an equal
      number of Group D COPD patients who besides the recommended treatment for stable
      disease received the supplement combination containing vitamin C 60 mg and zinc 5
      mg once daily, matched to the study subjects of the Group 1 by sex and age served
      as control (Group 2). RESULTS: Over the study period 57 exacerbations (24 in the
      Group 1 and 33 in the Group 2) were documented. A mean number of exacerbations
      over the study period was significantly lower in the Group1 (0.7 +/- 0.4) as
      compared to their mean number in the Group 2 (1.0 +/- 0.6) (P = 0.0218).
      Furthermore, a mean duration of exacerbations expressed in days needed for cure
      or clinical improvement (i.e. complete resolution of symptoms or return of the
      symptoms to their baseline severity) in the Group 1 (6.7 +/- 0.8 days) was
      significantly shorter than the mean duration of exacerbations in the Group 2 (7.4
      +/- 1.3 days) (P = 0.0118). There was not reported any adverse effect during the
      study period by study subjects from both examined groups. CONCLUSION: Our
      findings indicated that pleuran might impact the incidence and duration of
      bacterial exacerbations in patients with COPD. There is a need for further
      studies for more precise determination of the influence of pleuran on the course
      of COPD.

PMID- 29362613
TI  - Protective Effects of the Third Generation Vasodilatory Betaeta - Blocker
      Nebivolol against D-Galactosamine - Induced Hepatorenal Syndrome in Rats.
AB  - BACKGROUND: Renal dysfunction is very common in patients with advanced liver
      cirrhosis and portal hypertension. The development of renal failure in the
      absence of clinical, anatomical or pathological causes renal of failure is termed
      hepatorenal syndrome (HRS). AIM: The present study was constructed to investigate
      the possible protective effects of nebivolol (Nebi) against D-galactosamine (Gal)
      induced HRS in rats. MATERIAL AND METHODS: Rats were treated with Nebi for ten
      successive days. On the 8th day of the experiment, they received a single dose of
      Gal. Serum levels of Cr, BUN, Na+ and K+ as well as AST, ALT, total bilirubin
      (TB), NH3 and endothelin-1 (ET-1) were determined following Gal administration.
      Moreover, renal and liver contents of MDA, GSH, F2-isoprostanes (F2-IPs), tumor
      necrosis factor-alpha (TNF-alpha), nuclear factor kappa-B (NF-kappaB), total
      nitric oxide (NO), in addition to activities of caspase-3 (Cas-3), heme oxygenase
      1 (HO-1), inducible and endothelial NO synthase (iNOS and eNOS) enzymes were also
      assessed. Finally, histopathological examination was performed. RESULTS: Nebi
      attenuated Gal-induced renal and hepatic dysfunction. It also decreased the Gal
      induced oxidative stress and inflammatory recruitment. CONCLUSION: Results
      demonstrated both nephroprotective and hepatoprotective effects of Nebi against
      HRS and suggested a role of its antioxidant, anti-inflammatory, anti-apoptotic
      and NO-releasing properties.

PMID- 29362616
TI  - Survival of Advanced Stage High-Grade Serous Ovarian Cancer Patients in the
      Republic of Macedonia.
AB  - AIM: The primary objective of the study was to evaluate the overall survival of
      women with advanced stage (Stage IIIA-IV) high-grade serous ovarian cancer in
      Macedonia. MATERIALS AND METHODS: The study was a cross-sectional medical record
      review of patients diagnosed with advanced stage HGSC. Patients were deemed
      eligible for inclusion if they were diagnosed with an advanced stage (Stage IIIA
      IV) HGSC of the ovary, fallopian tube or peritoneum between 2009 and 2015. The
      data were analyzed in a descriptive fashion and summary statistics were provided,
      as appropriate. Survival was calculated using the Kaplan-Meier method. RESULTS: A
      total of 81 eligible patients were identified and included in the study. The
      average overall survival in the studied cohort was 46.59 months (95%CI = 39.11
      54.06). Patients that were optimally debulked and patients that had a platinum
      free interval larger than 12 months had significantly longer survival in the
      current series (p < 0.001). CONCLUSION: the average overall survival of advanced
      stage HGSC patients in the studied series was 46.59 months (95%CI = 39.11-54.06).
      Patients aged 65 years or younger tended to live approximately ten months longer
      than patients older than 65 years, but this difference was not statistically
      significant. There was no difference in HGSC survival in the groups of patients
      with grade 2 and grade 3 disease. However, optimal surgical debulking and
      platinum sensitivity were associated with significantly better overall survival.

PMID- 29362615
TI  - Relationship between Vitamin D, Inflammation and Lung Function In Patients with
      Severe Uncontrolled Asthma.
AB  - BACKGROUND: Recently epidemiological studies showed that low vitamin D is linked
      to airway hyperresponsiveness, decreased lung function, poor asthma control, and
      steroid-resistant asthma. AIM: We investigated the relationship between Vitamin
      D, inflammation with circulating IL-33 and lung function in 30 patients with
      severe uncontrolled asthma. MATERIALS AND METHODS: The study included 30 patients
      with severe uncontrolled asthma. In each of them were measured serum levels of IL
      33 and Vitamin D by the ELISA method. The pulmonary function is measured by basic
      spirometry parameters, FEV1. The results were statistically elaborated according
      to the Pearson's Correlation Tests. RESULTS: The results showed statistically
      insignificant correlation between Vitamin D and IL-33, and Vitamin D with FEV1
      (Vit.D/IL-33; r = 0.11323, p = 0.551); (Vit.D/FEV1; r = -0.1005; p = 0.597)
      Correlation between IL-33 and FEV1 is negative but statistically significant (IL
      33/FEV1; r = -0.5248; p = 0.003). CONCLUSION: Because there are little studies
      about the link between vitamin D and asthma, further research to clarify the
      mechanism how vitamin D control the activity of CD4+ T cells and the related Th2
      type cytokines in the parthenogenesis of asthma.

PMID- 29362617
TI  - The Predictive Role of Procalcitonin On the Treatment of Intra-Abdominal
      Infections.
AB  - AIM: This study aims to evaluate the algorithm of procalcitonin (PCT) and its
      role on the duration of antibiotics prescription for intra-abdominal infections.
      MATERIALS AND METHODS: This study is a prospective controlled study that is
      conducted in groups of 50 hospitalised patients and 50 controlled group patients.
      RESULTS: The results indicated that the average duration of antibiotic delivery
      to the PCT group was -10.6 days (SD +/- 6.6 days), while in the control group 
      13.2 days (SD +/- 4.2 days). These data showed a significant difference in the
      duration of antibiotic therapy and the monitoring role of PCTs in the prediction
      success of antibiotic treatment. The antibiotic delivery was longer in the septic
      shock 17 (SD +/- 11.7) that corresponds to high PCT values of 67.8 (SD +/- 50.9).
      Recurrence of the infection after the cessation of antibiotics occurred in 2
      cases (4%) in the standard group, while it occurred in 3 cases (6%) in the
      control group. CONCLUSION: The treatment of the intra-abdominal infections based
      on the PCT algorithm shortens the duration of antibiotic treatment and does not
      pose a risk for the recurrence of the infection.

PMID- 29362618
TI  - Correlation between the Montreal Cognitive Assessment-Indonesian Version (Moca
      INA) and the Mini-Mental State Examination (MMSE) in Elderly.
AB  - BACKGROUND: As the rapid growth of the elderly population and the increased
      prevalence of Alezheimer's Disease and related disorders, there is an increasing
      need for effective cognitive screening. The Mini Mental State Examination (MMSE)
      is the most frequently used screening test of cognitive impairment because of its
      convenience. The Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) has
      been validated and recently been used as a cognitive screening tool. OBJECTIVES:
      The aim of this study was to compare the MMSE and MoCA-INA scores and to
      determine the correlation between the MMSE and MoCA-INA scores in elderly.
      MATERIAL AND METHODS: This was a cross-sectional study including 83 elderly
      subjects from November 2016 until June 2017. We performed MMSE and MoCA-INA for
      assessment of cognitive function and the time between each test was at least 30
      minutes. RESULTS: The study included 83 subjects which were consisted of 46
      (55.4%) males and 37 (44.6%) females. The mean age was 69.19 +/- 4.23 ranging
      from 65 to 79 years old. The average MMSE scores was 24.96 +/- 3.38 (range 14 to
      30). The average MoCA-INA scores was 21.06 +/- 4.56 (range 5 to 30). The Pearson
      correlation coefficient between the scores was 0.71 (p<0.005). There were no
      significant differences of both scores based on history of hypertension, diabetes
      mellitus and previous stroke, but there was a significant difference in MMSE
      scores based on level of education. CONCLUSION: The MoCA-INA score showed a good
      correlation with the MMSE score. Both tests showed comparable results but MoCA
      INA showed lower average with wider range of scores.

PMID- 29362619
TI  - Kosovo's Experience for Children with Feeding Difficulties after Cardiac Surgery
      for Congenital Heart Defect.
AB  - BACKGROUND: A feeding disorder in infancy and during childhood is a complex
      condition involving different symptoms such as food refusal and faddiest, both
      leading to a decreased food intake. AIM: We aimed to assess the prevalence and
      predictor factors of feeding difficulties in children who underwent cardiac open
      heart surgery in neonatal period and infancy. We address selected nutritional and
      caloric requirements for children after cardiac surgery and explore nutritional
      interdependence with other system functions. METHODS: This was a retrospective
      study in a tertiary referral hospital, and prior approval from the institutional
      ethics committee was obtained. Information for 78 children (42 male and 36
      female) was taken from patients charts. Data were analysed with descriptive
      statistics and logistic regression. RESULTS: From a cohort of analysed children
      with feeding problems we have occurred in 23% of such cases. At the time of the
      study, refusal to eat or poor appetite was reported as a significant problem in
      19 children and subnormal height and weight were recorded in 11 children. Early
      neonatal intervention and reoperation were identified as risk factors for latter
      feeding difficulties or inadequate intake. Children with feeding problems also
      tended to eat less than children without feeding problems. There was a trend
      towards more feeding problems in patients with chromosomal abnormalities or other
      associated anomalies. CONCLUSION: Feeding disorder is often and a frequent long
      term sequel in children after neonatal or early infancy heart surgery. Patients
      with chromosomal and associated anomalies who underwent multiple cardiac
      surgeries are at risk of developing feeding difficulties.

PMID- 29362620
TI  - Compare Of the West Syndrome with Other Syndromes in the Epileptic Encephalopathy
      - Kosovo Experience.
AB  - BACKGROUND: West Syndrome (WS) represents as a specific epileptic encephalopathy
      characterised with a unique type of attacks, called infantile spasms, severe
      forms of abnormalities in electroencephalographic (EEG) records as a
      hypsarythmias and delays in the psychomotoric development. The characteristics of
      the disease, mostly affecting male gender, are infantile spasms and typical
      findings in EEG as a hypsarythmia. Infantile spasms are a consequence of many
      factors in the undeveloped brain. AIM: We aimed: (1) to see the incidence of the
      illness and the spreading out because of gender in rapport with other syndromes
      in the epileptic encephalopathies group; (2) to show principles of the treatment
      for the illness; and (3) to present the effects of the disease in the psycho
      motoric development of affected children. METHODS: The study was designed as a
      cross-sectional study of the patients with epileptic encephalopathies, treated in
      Paediatric Clinic in Prishtina, from 1st of January 2013 until the 31st of
      December 2015. RESULTS: From the cohort group of 97 children diagnosed with
      epileptic encephalopathies, in 14 of them clinical and EEG signs of WS were
      noted. The earliest age of disease manifestation was 74 days (+/- 63.8 days). On
      the group of children with WS, 13 of them with Natrium Valpropat were treated,
      with the doses of 301.9 mg (+/- 64.1). From the cohort group, in 89 children
      (91.8%) psychomotoric retardation was documented, within the higher reoccurrence
      in the undifferentiated epileptic encephalopathies (96%) and the WS (78.6%).
      CONCLUSION: WS is a frequent disease of the encephalopathies with the
      epileptogenic framework. The resistance in anticonvulsive therapy is huge, and
      psychomotoric retardation follows a big percentage of children with this
      syndrome.

PMID- 29362621
TI  - Assessment of the Correlation between Severity of Coronary Artery Disease and
      Waist-Hip Ratio.
AB  - AIM: This study was conducted to investigate the correlation between waist/hip
      ratio (WHR) as a measurement of obesity and severity of coronary artery disease
      (CAD) assessed by angiography in Kosovo. METHODS: The study included 82 patients
      with suspected or known CAD who were referred for coronary angiography. All
      patients were subjected to full individual medical history, clinical examination
      including measurement of arterial blood pressure, body weight, height, body mass
      index (BMI), waist circumference, hip circumference, waist/hip ratio, and
      waist/height ratio. Coronary angiography was performed using standard techniques
      to determine the presence and severity of coronary artery lesions with the
      Gensini score. RESULTS: Among the 82 patients in the study, the mean age in the
      CAD group was 66.76 +/- 9.12 years and the mean age in the non-CAD group was
      64.80 +/- 8.30 years. Patients in the CAD group had a mean BMI of 28.17 +/- 3.32
      kg/m2 and those in the non-CAD group had a mean BMI of 28.76 +/- 4.68 kg/m2.
      Patients in the CAD group had a mean waist/height ratio of 1.76 +/- 7.56 and
      those in the non-CAD group had a mean waist/height ratio of 0.57 +/- 0.08.
      Patient in the CAD group had a mean waist/hip ratio of 0.93 +/- 0.06 and those in
      the non-CAD group had a mean waist/hip ratio of 0.88 +/- 0.07. Thirty-seven
      patients (45.1%) had no coronary artery disease (Gensini score = 0), 15 (18.3%)
      had mild disease (Gensini score = 1-32), 14 (17.1%) had moderate disease (Gensini
      score = 32-58), and 16 (19.5%) had severe disease (Gensini score >= 58).
      CONCLUSION: There was a significant positive correlation between waist/hip ratio
      and presence of CAD in Kosovar patients.

PMID- 29362622
TI  - Apelin, Nitric Oxide and Vascular Affection in Adolescent Type 1 Diabetic
      Patients.
AB  - AIM: To evaluate the relationship of apelin and nitric oxide (NO) to endothelial
      dysfunction in type 1 diabetics. PATIENTS AND METHODS: Sixty two type 1 diabetics
      and 30 healthy age and sex matched controls were included. Blood samples for
      apelin, NO, glycosylated hemoglobin (HbA1c), and lipid profile were collected.
      Albumin/creatinine ratio was assessed in urine. Flow mediated dilatation (FMD)
      via ultrasound was done. RESULTS: The mean age of diabetics were 16.3 +/- 1.5 yrs
      (14.0 - 19.0 yrs), and duration of disease, were 9.4 +/- 2.9 yrs (5.0 - 16.5
      yrs). FMD and FMD/nitrate mediated dilatation (NMD) ratio were lower in
      diabetics. NO was decreased, while apelin and albumin/creatinine ratio were
      increased significantly in diabetics. There was a positive correlation between
      apelin and HbA1c. On the contrary, NO had a negative correlation with HbA1c,
      albumin/creatinine ratio, LDL-c and OxLDL. CONCLUSION: Diabetic patients had
      endothelial dysfunction and high apelin level, with no related to each other.
      High level of apelin is associated with bad glycemic control. Obesity had no role
      to increase in apelin level. NO is related to diabetic nephropathy and
      atherosclerosis. We recommend a further large study to evaluate the relationship
      of apelin with endothelial dysfunction.

PMID- 29362623
TI  - The Prevalence and Risk Factors of Early Arrhythmias Following Pediatric Open
      Heart Surgery in Egyptian Children.
AB  - AIM: This study aimed to assess the prevalence of early postoperative arrhythmias
      after cardiac operation in the pediatric population, and to analyse possible risk
      factors. MATERIAL AND METHODS: Cross-sectional study included 30 postoperative
      patients, with age range four up to 144 months. They were selected from those
      admitted to the Cardiology Unit in the Pediatric department of Ain Shams
      University hospitals, after undergoing cardiopulmonary bypass (CPB) surgery for
      correction of congenital cardiac defects. All patients had preoperative sinus
      rhythm and normal preoperative electrolytes levels. All patients' records about
      age, weight, type of surgery, intraoperative arrhythmias, cardiopulmonary bypass
      time, ischemic time and use of inotropic drugs were taken before they were
      admitted to the specialised pediatric post-surgery intensive care unit (ICU).
      RESULTS: Arrhythmia was documented in 15 out of 30 patients (50%). Statistically
      significant difference between the arrhythmic and non-arrhythmic group were
      recorded in relation to the age of operation (23 vs 33 months), weight (12 vs. 17
      kg), ischemic time (74.5 vs. 54 min), cardiopulmonary bypass time (125.5 vs.
      93.5min), inotrope use (1.6 vs. 1.16) and postoperative ICU stay (5.8 vs. 2.7
      days), P<0.05. CONCLUSION: Early postoperative arrhythmias following surgery for
      congenital heart disease are relatively frequent in children (50%). Younger age,
      lower body weight, longer ischemic time and bypass time, and more inotrope use
      are all risk factors for postoperative arrhythmias and lead to increase the
      hospital stay.

PMID- 29362624
TI  - Profile of Skin pH in Leukaemia's Children with Chemotherapy Treatments at Haji
      Adam Malik General Hospital, Medan.
AB  - BACKGROUND: One of the treatments for leukaemia is chemotherapy. Side effects and
      toxicity of this treatment can be seen on the skin, adnexal, and mucous
      membranes. They might increase potential hydrogen (pH) value on the skin surface,
      therefore, disrupting epidermal barrier defences. AIM: To describe the pH of the
      skin in children with leukaemia who received chemotherapy. SUBJECT AND METHOD:
      This study was an observational descriptive, cross-sectional study, conducted
      from March until December 2016 with 32 children with leukaemia who treated at
      Haji Adam Malik General Hospital, Medan as subjects. Skin pH was measured by a pH
      meter. RESULT: We found mean skin pH in ALL (6.28 +/- 0.58), CML (5.9 +/- 0) and
      AML (6.5 +/- 0.50). The mean skin pH after 1-5 weeks of chemotherapy was 6.13 +/-
      0.49, at 6-10 weeks (6.32 +/- 0.51), and at 11-15 weeks (7.12 +/- 0.36). The mean
      skin pH of patients with two drugs (5.98 +/- 0.44), four drugs (6.28 +/- 0.55),
      and six drugs (6.63 +/- 0.56). CONCLUSION: The highest mean of skin pH were
      obtained in AML group, 11-15 weeks length of chemotherapy and group with six
      drugs regimen.

PMID- 29362625
TI  - A Comparison of the Quality of Sleep between Pre and Post-Surgery Cervical
      Herniated Nucleus Pulposus Patients Utilizing the Anterior Discectomy Method.
AB  - BACKGROUND: Herniated Nucleus Pulposus (HNP) is the prolapse of the
      intervertebral disk through a tear in the annulus fibrosus. This causes nerve
      root compression with clinical pain manifestation and affects the quality of
      sleep. AIM: The aim of this study was find out the comparison in the quality of
      sleep between before (pre) and after (post) surgery cervical HNP patients.
      METHODS: This study was a retrospective cohort study. Ninety patients were asked
      to complete the Pittsburgh Sleep Quality Index (PSQI) questionnaire. All data
      which has been computed were analysed with the McNemar test. RESULT: The outcome
      reveals that from 90 patient's cervical HNP, 81 (90%) were 40 years old age group
      and 66 (73.3%) of them were women. The result showed that 66 (73.3%) patients
      have a bad sleep quality before surgery. Surgery has increased the quality of
      sleep after surgery 66 (73.3%) patients had good sleep quality. There was a
      significant difference in the quality of sleep pre and post operation (p =
      0.001). CONCLUSION: There was a significant difference in the quality of sleep
      between pre and post operation cervical HNP patient utilising anterior discectomy
      methods.

PMID- 29362626
TI  - Comparative Study on Adding Pioglitazone or Sitagliptin to Patients with Type 2
      Diabetes Mellitus Insufficiently Controlled With Metformin.
AB  - BACKGROUND: Diabetes mellitus is a progressive disorder that often requires
      combination therapy. AIM: This study aimed to compare and study of add-on
      sitagliptin versus pioglitazone in patients with type 2 diabetes inadequately
      controlled with metformin. METHODS: This 12-week, randomised, open-label and
      single centre study compared sitagliptin (100 mg daily, n = 80) and pioglitazone
      (30 mg daily, n = 80) in type 2 diabetic patients whose disease was not
      adequately controlled with metformin. RESULTS: The mean change in HbA1c from
      baseline was -1.001 +/- 0.83 with sitagliptin and -0.75 +/- 1.20 with
      pioglitazone, and there were no significant difference between groups (P =
      0.132). The mean change in fasting blood sugar (FBS) was -18.48 +/- 33.32 mg/dl
      with sitagliptin and -20.53 +/- 53.97 mg/dl with pioglitazone, and there were no
      significant difference between groups (P = 0.773). Sitagliptin caused 1.08 +/-
      2.39 kg decrease in weight, whereas pioglitazone caused 0.27 +/- 2.42 kg increase
      in weight, with a between-group difference of 0.81 kg (P < 0.001). On the other
      hand, in sitagliptin group, there was greater improvement in lipid profile than
      pioglitazone group. CONCLUSION: Sitagliptin and Pioglitazone demonstrated similar
      improvements in glycemic control in type 2 diabetes mellitus patients whose
      diabetes had been inadequately controlled with metformin. Nevertheless,
      sitagliptin was more effective than pioglitazone regarding lipid and body weight
      change.

PMID- 29362627
TI  - PET Scan Misses Cutaneous Melanoma Metastasis with Significant Tumour Size and
      Tumour Thickness.
AB  - BACKGROUND: Although PET-scan is an advanced, innovative and widely used method
      for monitoring patients with different types of cancer diseases, it is important
      to note that its application in patients with cutaneous melanoma is limited and
      should be reconsidered. CASE REPORT: To affirm this new statement, we are
      presenting a case from our clinical practice of a patient with melanoma of the
      interdigital space (with resected in sano primary melanoma and performed complete
      lymphadenectomy) that showed locoregional and systemic progression in two months
      post operation. The PET scan performed within the second hospitalization (and
      before the second operation) did not detect the presence of any cutaneous
      metastases, which were clinically and histologically verified after the second
      operative procedure. CONCLUSIONS: This data suggests that shortly more reliable
      and sensitive imaging methods for monitoring patients with cutaneous melanoma
      should be found. Having in mind that our patient has been operated twice in the
      area of the primary lesion (as the surgical wound underwent secondary healing),
      theoretically, the abundant cicatrization could have led to reduced glucose
      uptake in the surrounded cancerous tissue. Monitoring of a larger number of
      patients with locoregional metastases and surgical interventions in different
      locations would shed light on the observations shared by us.

PMID- 29362628
TI  - Cerebral Venous Thrombosis in a Patient with Iron Deficiency Anemia and
      Thrombocytopenia: A Case Report.
AB  - AIM: To report a potential association of thrombosis, thrombocytopenia with iron
      deficiency anaemia. CASE REPORT: A 43-year-old female experienced an episode of a
      headache, with bilateral papilledema by neurological examination, magnetic
      resonance venography (MRV) brain showed cerebrovenous thrombosis (CVT), iron
      deficiency anaemia and thrombocytopenia by blood investigations, that was treated
      with iron supplementations and anticoagulation. CONCLUSION: In this patient,
      cerebrovenous thrombosis (CVT) was discovered in a patient with thrombocytopenia
      and iron deficiency anaemia and treated with iron supplements and
      anticoagulation, we concluded that thrombocytopenia is not a protective factor
      against thrombosis especially with iron deficiency anaemia.

PMID- 29362629
TI  - Primary Solitary Melanoma of the Lymphatic Nodes Or a Single Metastasis of
      Unknown Melanoma: Do We Need a New Staging System?
AB  - BACKGROUND: Malignant melanoma is a disease which has a cutaneous origin in 90%
      of the patients, but in rare cases, it could be discovered as secondary deposits
      with unknown primary site. Metastatic Malignant Melanoma occurs without a primary
      site in about 3% of all melanoma patients, and it could be divided into two main
      groups: metastatic lymph nodes' involvement or non-lymph nodes disease. The lack
      of unified classification and staging system, provided by AJCC (2009), as well as
      the lack for curtain diagnostic and therapeutic protocol, prompt us to raise the
      question what is the right way to precede in cases of metastasis of the lymph
      nodes, without evidence of a primary tumour? CASE REPORT: We report a case of 67
      years- old woman who presented in the dermatology clinic after a surgical removal
      of an enlarged lymph node in her left femoral area, verified histologically as a
      metastasis of melanoma. After a diagnostic refinement in the clinic, the
      diagnosis of metastasis of malignant melanoma was confirmed by histology
      revision. We use the presented case to create for the first time in the world
      literature a novel stereotype of thinking, which is also followed by a stereotype
      of clinical behaviour - gentle to the patient, but providing a certain amount of
      security and satisfaction for the medical staff. CONCLUSION: The affection of a
      single lymph node in the absence of a primary tumour should not automatically
      lead to the conclusion that it is a single metastasis, but rather a primary
      melanoma of the lymph nodes, in cases of a negative PET scan, for example. In
      these cases, the measuring of the tumour thickness should guide the further
      therapeutic behaviour and determine the approach.

PMID- 29362630
TI  - Spontaneous Anterior Lens Capsule Rupture Of a Patient with Alport Syndrome - A
      Case Report.
AB  - BACKGROUND: Alport syndrome is a progressive genetic disease which is
      characterised by glomerulonephritis, sensorineural deafness and ocular
      abnormalities. We aimed to present a clinical case of a patient with Alport
      syndrome with spontaneous anterior lens capsule rupture. CASE REPORT: A 16-year
      old male with histologically proven Alport syndrome was hospitalised in the
      Department of Ophthalmology, University Hospital "Prof. Stoyan Kirkovich", Stara
      Zagora with low vision, pain, redness, high IOP and rupture of the anterior
      lenticular capsule of the right eye. Phacoaspiration was successfully performed
      (Millenium, Bausch& Lomb, Rochester, New York, USA) with the bimanual irrigation
      aspiration system (Geuder AG, Heidelberg, Germany) with excellent visual results.
      CONCLUSION: As the syndrome is quite rare and can lead to diagnostic difficulties
      for the ophthalmologist complications such as spontaneous or traumatic rupture of
      the capsule are not uncommon. In such cases, phacoaspiration is an efficient
      method for clear lens extraction after ruptures of the anterior lenticular
      capsule of young patients with Alport syndrome.

PMID- 29362631
TI  - Prevalence of Oral Mucosal Lesions and Their Association with Severity of
      Psoriasis among Psoriatic Patients Referred To Dermatology Clinic: A Cross
      Sectional Study in Kashan/Iran.
AB  - BACKGROUND: Psoriasis is a common inflammatory papulosquamous disease of the skin
      with unknown aetiology that may be associated with the abnormal T-cell function.
      AIM: This study was aimed to determine the prevalence of oral mucosal lesions and
      their associations with severity of psoriasis in psoriatic patients attending the
      dermatologic clinic of Shahid Beheshti Teaching Hospital at Kashan, Iran.
      METHODS: In this cross-sectional descriptive analytic study, all consecutive
      patients with psoriasis who referred to the dermatologic clinic at the Shahid
      Beheshti Hospital of Kashan University of Medical Sciences in Kashan City/ Iran
      were enrolled. All patients were examined for the presence of oral lesions, and
      the clinical and epidemiological features of the disease were recorded in a
      questionnaire for each patient. A biopsy was taken from atypical suspected
      patients with oral lesions by an expert dermatologist. Data were analysed using
      the Statistical Package for Social Science (Version 18). Descriptive statistics
      tests; Cross tabulation and Chi-square with Fisher's exact test were used.
      RESULTS: Of total 177 psoriatic patients, 62 cases (35%) of patients were male,
      and 115 cases (65%) were female. Mean age of patients was 31.71 years. The oral
      lesion was seen in 83 cases (46.9%). Fissure tongue (28.2%) and geographic tongue
      (4.5%) were the most common oral lesions. The prevalence of oral lesions in
      patients with psoriasis significantly was associated with age, history of oral
      lesions, and with the onset of the oral lesions (P < 0.05). The most common form
      of psoriasis was chronic plaque form (Psoriasis Vulgaris) observed in 147 cases
      (83.1). The majority of patients (67.2%) were suffering from a mild form of the
      disease. Psoriasis Area and Severity Index (PASI) score of most patients was
      mild. CONCLUSIONS: The prevalence of oral lesions such as Fissure tongue and
      geographic tongue is higher in psoriatic patients suggests further studies for
      approving the clinical importance of these apparently nonspecific lesions as
      possible predictors or markers of the severity of the cases suspected to
      Psoriasis disease.

PMID- 29362632
TI  - Temporomandibular Disorders Treatment with Correction of Decreased Occlusal
      Vertical Dimension.
AB  - BACKGROUND: The term decreased occlusal vertical dimension refers to the reduced
      distance between two anatomical points while the teeth are in a state of
      occlusion. The development of this situation is about some parafunctional
      activities of the masticatory system. AIM: To evaluate the value of decreased
      occlusal vertical dimension in cases with temporomandibular disorder and to
      follow up the influence of corrective treatment with occlusal splints and
      definitive prosthetic construction upon the elimination of clinical symptoms.
      MATERIAL AND METHODS: Eight cases with decreased occlusal vertical dimension
      accompanied with temporomandibular disorders were treated with an occlusal
      splint, as part of reversible occlusal treatment. After reducing, or complete
      elimination of the symptoms related to problems of decreased occlusal vertical
      dimension, the definitive prosthetic therapy was performed. RESULTS: The mean
      value of decreased occlusal vertical dimension in our patients is 8.5 mm, and the
      mean value of therapy time with an occlusal splint in these patients was 3.5
      months. CONCLUSION: Occlusal splint is a part of reversible occlusal therapy in
      cases with decreased occlusal vertical dimension. After reducing the symptoms
      related to decreased occlusal vertical dimension definitive prosthetic therapy
      can be done.

PMID- 29362633
TI  - Testing the Effect of Aggressive Beverage on the Damage of Enamel Structure.
AB  - BACKGROUND: Dental erosion is a common problem in modern societies, owing to the
      increased consumption of acid drinks such as soft drinks, sports drinks, fruit
      juice. Examining the enamel surface with the Atomic Force Microscopy (AFM)
      enables more precise registering and defining the changes of enamel surface
      structure and microhardness. This method can be used to compare the efficiency of
      application of different preventive and therapy materials and medicaments in
      dentistry. The chronic regular consumption of low pH cola drinks encouraged the
      erosion of the teeth. The loss of anatomy and sensitivity are direct results of
      acid cola dissolving coronal tooth material. Under the influence of coca cola, a
      change of crystal structure and nanomorphology on enamel surface occurs. AIM:
      This paper reflects dental damage from abusive cola drinking, and the clinical
      presentation can be explained from data presented in this thesis. MATERIAL AND
      METHODS: The trial was conducted on a total of 40 extracted teeth which were
      divided into two groups treated with the solution of coca cola during 5 minutes,
      and then prepared and tested with a standard AFM procedure, type SPM-5200.
      Quantitative analysis was performed by comparing the roughness parameters (Ra) of
      the treated and non-treated sample. RESULTS: Based on the test of a hypothesis of
      the existence of differences between the treated and untreated sample, with an
      application of a t-test, it is shown that there are statistically highly
      significant differences between Ra of the treated sample with a 5-minute
      treatment of coca cola and Ra of the same sample without the treatment.
      CONCLUSION: Use of AFM enables successful monitoring of changes on enamel surface
      as well as the interpretation of the ultrastructural configuration of the crystal
      stage and the damage created under the influence of different external factors.

PMID- 29362634
TI  - The Effect of Strontium Ranelate Gel on Bone Formation in Calvarial Critical Size
      Defects.
AB  - AIM: The current study was designed to investigate the effectiveness of locally
      applied Strontium ranelate to induce bone formation. MATERIALS AND METHODS: Forty
      eight female rats were divided into six groups (eight rats in each group): The
      three test groups included Strontium (SR) 2.5 mg, 5 mg and 10 mg that was
      dissolved in methylcellulose gel. The control groups included methylcellulose,
      simvastatin 5 mg and a negative control where the defect was left to heal without
      any intervention. At 44 days the groups were sacrificed, and the bone defects
      were assessed histomorphometically to assess bone formation. The data was
      statistically analysed. RESULTS: There was a statistically significant difference
      in the amount of new bone formation between all groups, where the 2.5 mg SR group
      showed the highest median bone percentage, is 41.95 %, followed by the 5, and 10
      mg SR demonstrating a median bone are a percentage of 39.89%, and 30.19%
      respectively. Simvastatin showed a median bone percentage of 36.07 %, while the
      methylcellulose and the negative control groups demonstrated the lowest median
      area percentage of 23.12 and 20.70 % respectively. CONCLUSIONS: The study showed
      that the local application of an SR could up-regulate the bone formation and may
      prove to be a cost-effective method of bone regeneration.

PMID- 29362635
TI  - Prosthodontic Rehabilitation of Patient with Anterior Hyper Function Syndrome.
AB  - BACKGROUND: The success of prosthetic rehabilitation in patients with removable
      dentures depends on the achievement of the aesthetics, phonetics and most of all,
      proper use in the mastication process. All the patients that receive removable
      prostheses need a feeding education program. They must cut the food into smaller
      pieces, extend the length of time necessary for chewing and place the food upon
      both the right and left sides of the mouth at once. Bilaterally chewing with
      dentures will contribute to increased efficiency and denture stability during
      mastication. Using the anterior teeth for biting, as a result of increased
      pressure on the anterior ridge may lead to the anterior hyperfunction syndrome.
      CASE REPORT: The patient requested dental rehabilitation in our clinic for
      prosthetic dentistry two and a half years ago. We examined him and made therapy
      plan, for complete removable maxillary denture and partial mandibular denture.
      Besides our instructions for proper use of dentures and necessity for regular
      controls, his next visit was after two and a half years. He came with enlarged
      tuberosity and papillary hyperplasia in the pre-maxillary region. After oral
      surgery treatment (laser removing of hyperplastic tissue) and a healing period of
      four weeks, we made indirect relining on the upper denture, re-occlusion and re
      articulation achieving weak contacts between the lower natural teeth and upper
      teeth of the complete denture. The patient was advised not to bite food with his
      anterior teeth, and avoid chewing very hard food which tends to imprint and
      displace dentures. CONCLUSION: Anterior hyperfunction syndrome with its high
      incidence is a disease with the need of interdisciplinary therapy approach. Fast
      diagnosis, thorough clinical examination using all available diagnostic tools,
      and choosing the right treatment is very challenging.

PMID- 29362636
TI  - Demographic and Clinical Features of Thyroid Carcinomas in Republic of Macedonia
      (1999-2010).
AB  - BACKGROUND: Thyroid carcinomas (TC) are the most common endocrine malignancies.
      In some parts of the world, the incidence of TCs has increased over the past few
      decades, especially in females according to some studies. AIM: We have set as the
      objective for our study to analyse the demographic, ultrasound features, thyroid
      hormonal status and frequency of thyroid carcinomas in the Republic of Macedonia
      according to histopathological type. MATERIALS AND METHODS: Retrospective
      analysis of medical data from all diagnosed and treated patients with TC at the
      Institute of Pathophysiology and Nuclear Medicine for the period 1999-2010 was
      performed. Demographic characteristics: age at diagnosis, gender,
      histopathological type of TC and from clinical features: US findings and thyroid
      hormonal state at initial examination and their distribution in eight state
      regions were evaluated. RESULTS: Total number of 204 patients with TC in the
      Republic of Macedonia was registered. Papillary thyroid carcinoma (PTC) was the
      most frequent with 131 pts (64.21%), follicular (FTC) with 13 pts (6.37%) was
      second thyroid malignoma, followed by medullary (MTC) with 12 pts (5.88%),
      anaplastic (ATC) 11 pts (5.39%) and the rarest types were Hurtle cell carcinoma
      and intrathyroid sarcoma with only 1 diagnosed case. Age varied widely from 7 yrs
      to 88 yrs age (average 47.9 +/- 16.6 yrs). PTC was more prevalent in younger age
      groups, while ATC was diagnosed in elderly patients. In all of the eight-country
      regions, the prevalence rate was higher for females than males (3:1) or 15.21/105
      female to 5.03/105 male prevalence rate. According to US appearance mostly TC was
      unilateral in 42.65% and multifocal in 7.84% with dimensions from 15 to 50 mm.
      CONCLUSION: There is an increase in incidence and prevalence rate of TCs in our
      country, mostly PTC, while reduction exists in the number of diagnosed cases of
      ATC and FTC, comparing with previous studies before iodine prophylaxis program.
      Different from described in the literature is female: male (4:1) ratio for ATC.
      According to US features, we can conclude that introduction of more detailed
      reporting system may improve diagnostic accuracy.

PMID- 29362637
TI  - The Value of Mobile Ultrasound Services in Rural Communities in South-South
      Nigeria.
AB  - AIM: This paper examines the activities of mobile services units including
      ultrasound services in rural and urban communities in the Calabar region of South
      South, Nigeria. MATERIALS AND METHODS: Consenting individuals were invited and
      attended five medical outreach activities in rural and urban areas of the Calabar
      region between January and June 2016. Abdomino-pelvic scans were done.
      Subsequently the results were analyzed. RESULTS: Five hundred and seventy-four
      (574) individuals had Abdomino-pelvic scans done, using a curvilinear probe to
      assess the abdomino-pelvic organs. The female to male ratio was 1.46:1. The age
      ranged from 1-78 years with a mean of 40.63 (standard deviation of 17.5). The
      commonest sonographic finding was uterine fibroids, 21 (8.1%). Fifty-four percent
      of the scans were normal. The commonest sonographic finding in men was prostatic
      enlargement. CONCLUSION: Medical outreach activities provided by mobile units
      provide much needed ultrasound services in poor resource settings in Nigeria.
      Significant clinical pathologies were identified at fairly high rates.

PMID- 29362638
TI  - Risk Factors for Early Preterm Birth at King Salman Armed Force Hospital in 2010.
AB  - AIM: To investigate risk factors for early preterm birth. METHODS AND MATERIAL: A
      retrospective comparative study was conducted at Tabuk, Kingdom of Saudi Arabia
      during the period from January to December 2010. Five hundred and ninety-five
      patient's files and delivery registry logbooks were reviewed, the following
      information was collected; demographic data, current and past obstetric
      histories. Then the early and late preterm births were compared for various risk
      factors. The Statistical Package for Social Sciences (SPSS version 22) was used.
      The Chi-square and t-test were used to test the statistical significance and a P
      value<0.05 considered significant. RESULTS: Prevalence of early preterm birth was
      found to be 2.5% in our study group. Women at risk for early preterm birth were:
      primigravidas (33.7% vs. 26.2% for control), P-value 0.039, OR 1.429 and 95% CI
      0.982 - 2.079); multiple gestations (87.7% vs. 95.1% for control, P-value 0.002,
      OR 0.368 and 95% CI 0.196 - 0.688); and patients with a prior history of
      placental abruption (3.7% vs. 1.0% for control, P-value 0.027, OR3.928 and 95% CI
      1.1360 - 13.586). CONCLUSIONS: Current study indicated that early preterm births
      differed from preterm as a whole; primigravida, multiple gestations and a history
      of placental abruption are independent risk factors for them.

PMID- 29362639
TI  - Management, Diagnostic and Prognostic Significance of Acetylcholinesterase as a
      Biomarker of the Toxic Effects of Pesticides in People Occupationally Exposed.
AB  - AIM: The paper presents research on the most common causes of exposure that leads
      to disorders of cholinesterase activity, as well as an overview of the results of
      cholinesterase activity with the poisoned people. MATERIAL AND METHODS: In a
      group of 35 acute poisoned patients by organophosphate compounds has led to
      inhibition of AchE. A total number of examined workers are 175 in the chemical
      industry and agricultural production in the area of Rasina District-Serbia.
      RESULTS: The results showed that among workers who are constantly exposed to
      pesticides, acetylcholinesterase is within the reference value. Having examined
      the medical records of these workers, it is noted that, at 72%, there is a slight
      fall of AchE activity, each year. The workers who had been exposed to pesticides
      at the time of testing had acetylcholinesterase regarding reference value, but
      52% of them had a few years ago significantly reduced the value of the activity
      of acetylcholinesterase, which was treated and then transferred to other jobs.
      The 48% of these workers had acetylcholinesterase regarding benchmarks or were
      transferred to other jobs, for a variety of other health problems. CONCLUSION:
      Using each pesticide should only deal with people who are well versed in the way
      of its use, as well as the way of protecting them from poisoning.

PMID- 29362640
TI  - Experiences of Barriers and Motivators to Weight-Loss among Saudi People with
      Overweight or Obesity in Qassim Region - A Qualitative Study.
AB  - BACKGROUND: Obesity has become a global health threat. Saudi Arabia ranks among
      the countries with high obesity and overweight rates. This study aims to explore
      experiences of Saudi people with overweight or obesity with a particular focus on
      the perceived barriers and motivators to weight loss. MATERIAL AND METHODS: We
      used a qualitative approach to recruiting a purposive sample using maximum
      variation sampling technique. Those who had previously attempted weight loss at
      least once were included in the study. In-depth interviews were conducted,
      transcribed and/ or audiotaped. Interviews continued until saturation was
      reached. The qualitative content analysis was performed. RESULTS: A total of 19
      males and 18 females participated in this study with a mean Body Mass Index (BMI)
      of 32.6 kg/m2. Their main triggers to weight loss were concerns about overall
      health and the desire to improve their looks. Declining motivation, lack of
      family support and unhealthy eating during social gatherings were perceived as
      the main barriers. Motivating factors included concerns about health, family
      support, and availability of exercise facilities. CONCLUSION: Factors responsible
      for a successful weight- loss is context-specific. This study has shown several
      barriers as well as motivators, which play an important role in weight reduction
      and maintenance.

PMID- 29362641
TI  - Public Health Profile of Road Traffic Accidents in Kosovo 2010-2015.
AB  - AIM: To determine the characteristics of the Socio-medical profile of road
      traffic accidents in Kosovo, between 2010 and 2015 year. STUDY DESIGN:
      Retrospective study. METHODS: A descriptive method based on the database of road
      traffic accidents from the National Police of Kosovo. RESULTS: In Kosovo for the
      period 2010-2015, on average, the yearly number of road traffic accidents is
      18437 with mortality rate 7.4 per 100000 and lethality of 1.5%. The highest
      number of fatal cases are drivers and above 19 years old with more than 80%.
      Among injured significantly highest percentage is among passengers for all years
      and above 19 years old. Road traffic accident with a vehicle occurs most
      frequently, with approximately over 70%, mostly on dry road 72.9% and clear
      weather 71.1%. The driver is the contributing factors of road traffic accidents
      on average 99.3% whereas climatic conditions only 0.5%, with over 50% of crashes
      occurring in urban road 56.2%, mostly during Monday 16.0% and in the afternoon
      rush hours between 14.00-18.00 with 31.0%. CONCLUSIONS: There is a slight
      decrease in the mortality rate of 0.10/00 and lethality rate of 0.1% each year,
      whereas there is an increase of 21.50/00 for traumatism rate for each year.

PMID- 29362642
TI  - Subclinical Hypothyroidism - Whether and When To Start Treatment?
AB  - Subclinical hypothyroidism represents a state with increased values of thyroid
      stimulating hormone (TSH) and normal values of thyroxine (T4) and
      triiodothyronine (T3). The disorder is asymptomatic, and the diagnosis is made
      based on the results of laboratory findings when the level of TSH reaches values
      above 4.0 mU/l. It is still subject to debate whether patients with subclinical
      hypothyroidism are at increased risk of cardiovascular disease, neuropsychiatric
      and neuromuscular disorders. Studies have shown that the appearance of general
      symptoms and complications are more common in patients whose values of TSH are
      above 10 mU/l. Therefore, the initiation of therapy with levothyroxine, which is
      the foundation of substitution therapy, is advised in patients whose TSH is >10
      mU/l. As for patients whose values of TSH are from 4.0 to 10.0 mU/l and who make
      up 90% of the patients with subclinical hypothyroidism, further research is
      needed to determine the effects of the disorder and levothyroxine therapy on the
      health. Until then, the introduction of the substitution therapy in patients with
      TSH which is <10 mU/l should be considered in the case of the presence of general
      symptoms, anti-thyroid antibodies, increased lipids and other risk factors,
      goitre, pregnancy, ovarian dysfunction and infertility.

PMID- 29362643
TI  - Endoscopic Removal of a Giant Complicated Hyperplastic Gastric Polyp.
AB  - The patient, a 40-year-old male, was referred to our clinic with intermittent
      nausea, vomiting and symptomatic anemia for 4 months. Notable hematological
      indices were low hemoglobin levels of 9.6 g/dl and hematocrit levels of 35.8%,
      while after receiving two units of concentrated red blood cells, at discharge;
      they achieved levels of 15.2 g/dl and 42.3%, respectively.
      Esophagogastroduodenoscopy revealed a 3 cm antral pedunculated polyp, prolapsing
      into pylorus thus causing intermittent pyloric obstruction and anemia.
      Histological examination revealed a hyperplastic polyp without evidences of
      malignancy. No atrophy, metaplasia, dysplastic changes or Helicobacter pylori
      infection were detected in samples taken from the antrum and the corpus; however,
      the examination provided evidence for gastritis. Follow-up endoscopy was provided
      after 12 weeks to see polypectomy site after a course of Pantoprazole
      administration, and to define symptom-free time after polypectomy. Endoscopic
      removal of complicated gastric polyps should be considered at the time of initial
      diagnostic endoscopy. Endoscopic resection of polyps enables to determine the
      exact histopathologic type as well as to effectively treat symptomatic gastric
      outlet obstruction and anemia.

PMID- 29362644
TI  - Effects of Language Background on Gaze Behavior: A Crosslinguistic Comparison
      Between Korean and German Speakers.
AB  - Languages differ in how they categorize spatial relations: While German
      differentiates between containment (in) and support (auf) with distinct spatial
      words-(a) den Kuli IN die Kappe stecken ("put pen in cap"); (b) die Kappe AUF den
      Kuli stecken ("put cap on pen")-Korean uses a single spatial word (kkita)
      collapsing (a) and (b) into one semantic category, particularly when the spatial
      enclosure is tight-fit. Korean uses a different word (i.e., netha) for loose-fits
      (e.g., apple in bowl). We tested whether these differences influence the
      attention of the speaker. In a crosslinguistic study, we compared native German
      speakers with native Korean speakers. Participants rated the similarity of two
      successive video clips of several scenes where two objects were joined or nested
      (either in a tight or loose manner). The rating data show that Korean speakers
      base their rating of similarity more on tight- versus loose-fit, whereas German
      speakers base their rating more on containment versus support (in vs. auf).
      Throughout the experiment, we also measured the participants' eye movements.
      Korean speakers looked equally long at the moving Figure object and at the
      stationary Ground object, whereas German speakers were more biased to look at the
      Ground object. Additionally, Korean speakers also looked more at the region where
      the two objects touched than did German speakers. We discuss our data in the
      light of crosslinguistic semantics and the extent of their influence on spatial
      cognition and perception.

PMID- 29362645
TI  - The Effects of Similarity on High-Level Visual Working Memory Processing.
AB  - Similarity has been observed to have opposite effects on visual working memory
      (VWM) for complex images. How can these discrepant results be reconciled? To
      answer this question, we used a change-detection paradigm to test visual working
      memory performance for multiple real-world objects. We found that working memory
      for moderate similarity items was worse than that for either high or low
      similarity items. This pattern was unaffected by manipulations of stimulus type
      (faces vs. scenes), encoding duration (limited vs. self-paced), and presentation
      format (simultaneous vs. sequential). We also found that the similarity effects
      differed in strength in different categories (scenes vs. faces). These results
      suggest that complex real-world objects are represented using a centre-surround
      inhibition organization. These results support the category-specific cortical
      resource theory and further suggest that centre-surround inhibition organization
      may differ by category.

PMID- 29362646
TI  - Different Paths to Different Strategies? Unique Associations Among Facets of the
      Dark Triad, Empathy, and Trait Emotional Intelligence.
AB  - Emotional deficits, such as limited empathy, are considered a fundamental aspect
      of the Dark Triad traits (narcissism, Machiavellianism, and psychopathy).
      However, the nature and extent of such deficiencies seem to vary among dark
      personalities. By applying multidimensional measures of empathy, emotional
      intelligence, and the Dark Triad, we aimed to investigate in more detail how
      individuals high in various dark traits understand and evaluate emotions. Results
      indicated that each trait, and, moreover, each facet thereof entailed unique
      emotional deficiencies. Narcissism was positively associated with trait emotional
      intelligence, whereas the secondary factor of psychopathy was associated
      negatively. With respect to empathy, only primary psychopathy was linked to an
      overall deficit, while a positive relationship was found between Machiavellianism
      and the perspective-taking facet of cognitive empathy. We argue that the specific
      emotional limitations of the Dark Triad traits might contribute to the successful
      deployment of different socially aversive strategies.

PMID- 29362647
TI  - Nonspecific Retroactive Interference in Children and Adults.
AB  - Retroactive interference (RI) is a primary source of forgetting and occurs when
      new information disrupts or damages an existing memory. Prior research has shown
      that children are susceptible to RI when the to-be-remembered and interfering
      information are similar, but it is unclear whether they are also vulnerable to
      nonspecific RI . This form of interference occurs when a memory is disrupted by
      an unrelated and dissimilar distractor task, and the present study explored six-
      and seven-year-olds susceptibility to such nonspecific RI. In two experiments,
      participants learnt a list of words and completed a free recall test 5 min later.
      During the interval, participants either remained quiet (the control condition)
      or completed spot-the-difference puzzles (the interference condition). In
      Experiment 1, the children were highly susceptible to nonspecific interference,
      whereas a sample of adults were not affected by the interfering task. However,
      when a new sample of children were given more time to encode and retrieve the
      words in Experiment 2, they were able to resist interference. Nonspecific RI can
      damage children's memory, but they do have the ability to prevent this form of
      interference in certain circumstances.

PMID- 29362648
TI  - Outcome of esophageal cancer in the elderly - systematic review of the
      literature.
AB  - Introduction: As the population ages, the number of elderly patients with
      esophageal cancer increases. Esophageal cancer has a poor prognosis and is
      associated with decreased life quality. Aim: To review the literature about the
      outcome of esophageal cancer in patients over 65. Material and methods: Articles
      published between January 2006 and November 2016 in the PubMed/Medline and
      ResearchGate databases were reviewed. Nineteen retrospective studies were
      included. Results: Six thousand seven hundred and twenty-nine patients over 65
      were analyzed. Thirty-day mortality ranges from 3.2% to 8.1%. Overall 5-year
      survival rates range from 0% to 49.2%, and the median survival rate ranges from
      9.6 to 108.2 months. The incidence of complications in the surgery group ranges
      from 27% to 69%. Chemoradiotherapy grade >= 3 toxicity was observed in 22-36% of
      patients. Conclusions: Chronological age seems to have little influence on
      outcome of esophageal cancer. Open esophagectomy seems to be the mainstay of
      treatment for patients with esophageal cancer, regardless of age. There is still
      high mortality and morbidity involved in this procedure. To reduce them, some
      less invasive methods are being trialed.

PMID- 29362649
TI  - Long-term follow-up results of umbilical hernia repair.
AB  - Introduction: Multiple suture techniques and various mesh repairs are used in
      open or laparoscopic umbilical hernia (UH) surgery. Aim: To compare long-term
      follow-up results of UH repair in different hernia surgery groups and to identify
      risk factors for UH recurrence. Material and methods: A retrospective analysis of
      216 patients who underwent elective surgery for UH during a 10-year period was
      performed. The patients were divided into three groups according to surgery
      technique (suture, mesh and laparoscopic repair). Early and long-term follow-up
      results including hospital stay, postoperative general and wound complications,
      recurrence rate and postoperative patient complaints were reviewed. Risk factors
      for recurrence were also analyzed. Results: One hundred and forty-six patients
      were operated on using suture repair, 52 using open mesh and 18 using
      laparoscopic repair technique. 77.8% of patients underwent long-term follow-up.
      The postoperative wound complication rate and long-term postoperative complaints
      were significantly higher in the open mesh repair group. The overall hernia
      recurrence rate was 13.1%. Only 2 (1.7%) patients with small hernias (< 2 cm) had
      a recurrence in the suture repair group. Logistic regression analysis showed that
      body mass index (BMI) > 30 kg/m2, diabetes and wound infection were independent
      risk factors for umbilical hernia recurrence. Conclusions: The overall umbilical
      hernia recurrence rate was 13.1%. Body mass index > 30 kg/m2, diabetes and wound
      infection were independent risk factors for UH recurrence. According to our study
      results, laparoscopic medium and large umbilical hernia repair has slight
      advantages over open mesh repair concerning early postoperative complications,
      long-term postoperative pain and recurrence.

PMID- 29362650
TI  - Single port access for laparoscopic lateral segmentectomy.
AB  - Introduction: Single-port access laparoscopic lateral segmentectomy (LLS) has
      been developed as a novel minimally invasive surgery. We have experience with
      this LLS technique. Aim: To report our technique and patients' postoperative
      course in a series of single-port access LLS performed in our department. We also
      examine the cosmetic outcome, safety, and utility of the procedure. Material and
      methods: Between February 2010 and October 2016, 54 patients who underwent single
      or multiple-port laparoscopic or open lateral segmentectomy (LS) were
      retrospectively analyzed with respect to cosmetic outcome, safety, and utility.
      Results: In the single LLS group, the laparoscopic procedure was successfully
      completed for all 14 patients. The median operative time was significantly
      shorter in the single LLS group (123 min; range: 50-270 min) than in the other
      groups. Estimated blood loss was also significantly lower in the single LLS group
      (10 ml; range: 0-330 ml). During the first 7 postoperative days, the visual
      analog scale pain score and the use of additional analgesia were not
      significantly different between groups. The single LLS group had a 7.1%
      complication rate (Clavien-Dindo classification > IIIA); this was not
      significantly different between groups. Conclusions: Single-port access LLS is a
      procedure with excellent cosmetic results, although, with regard to invasiveness,
      there are no major differences from conventional LLS.

PMID- 29362651
TI  - Does previous open surgical experience have any influence on robotic surgery
      simulation exercises?
AB  - Introduction: Within the last years, there has been a trend in many hospitals to
      switch their surgical activity from open/laparoscopic procedures to robotic
      surgery. Some open surgeons have been shifting their activity to robotic surgery.
      It is still unclear whether there is a transfer of open surgical skills to
      robotic ones. Aim: To evaluate whether such transfer of skills occurs and to
      identify which specific skills are more significantly transferred from the
      operative table to the console. Material and methods: Twenty-five volunteers were
      included in the study, divided into 2 groups: group A (15 participants) - medical
      students (without any surgical experience in open, laparoscopic or robotic
      surgery); and group B (10 participants) - surgeons with exclusively open surgical
      experience, without any previous laparoscopic or robotic experience. Participants
      were asked to complete 3 robotic simulator console exercises structured from the
      easiest one (Peg Board) to the toughest one (Sponge Suture). Overall scores for
      each exercise as well as specific metrics were compared between the two groups.
      Results: There were no significant differences between overall scores of the two
      groups for the easiest task. Overall scores were better for group B as the
      exercises got more complex. For the intermediate and high-difficulty level
      exercises, most of the specific metrics were better for group B, with the
      exception of the working master space item. Conclusions: Our results suggest that
      the open surgical skills transfer to robotic skills, at least for the very
      beginning of the training process.

PMID- 29362652
TI  - Single center experience in laparoscopic treatment of gallbladder perforation.
AB  - Introduction: Gallbladder perforation (GBP) is a rare disease with potential
      mortality. Previous series have reported an incidence of approximately 2-11% and
      it still continues to be a significant problem for surgeons. Aim: To present our
      clinical experience with gallbladder perforation. Material and methods: The
      records of 2754 patients who received surgical treatment for cholelithiasis
      between 2010 and 2016 were reviewed retrospectively. One hundred thirty-three
      patients had gallbladder perforation. Age, gender, time from the onset of
      symptoms, diagnostic procedures, surgical treatment, morbidity and mortality
      rates were evaluated. Results: 15.78% of patients had a body mass index > 35.
      6.76% had chronic obstructive pulmonary disease, 6.76% had cardiac disease,
      10.52% had diabetes and 4.51% had sepsis. American Society of Anesthesiology
      scores were I in 54.13%, II in 35.33%, III in 6.01% and IV in 4.51% of the
      patients. 27.81% of patients were diagnosed during surgery. The perforation site
      was the gallbladder fundus in 69.17%, body in 17.30%, Hartman's pouch in 10.53%
      and cystic duct in 3% of patients. Treatment modalities were laparoscopic
      cholecystectomy in 82.71%, open cholecystectomy in 3%, percutaneous drainage
      catheters + laparoscopic cholecystectomy in 3%, laparoscopic cholecystectomy +
      fistula repair in 10.53% and open cholecystectomy + fistula repair in 0.75% of
      patients. Mean length of hospital stay was 1.69 days. Mortality and morbidity
      rates were 8.27% and 10.52%, respectively. Histopathology results were acute
      cholecystitis in 69.93%, chronic cholecystitis in 20.30% and acute exacerbation
      over chronic cholecystitis in 9.77% of patients. Conclusions: Appropriate
      classification and management of perforated cholecystitis is essential.
      Laparoscopic cholecystectomy is a safe and feasible method to decrease morbidity
      in gallbladder perforations.

PMID- 29362653
TI  - Reduced-port robotic total mesorectal resection for rectal cancer using a single
      port access: a technical note.
AB  - Introduction: Single-port laparoscopic surgery has some advantages, including
      improved cosmetic outcomes and minimized parietal trauma. However, pure single
      port laparoscopic rectal cancer surgery is challenging because of the
      difficulties in creating triangulation and applying the laparoscopic staplers
      with sufficient distal margins in the narrow pelvic cavity. Recently, a reduced
      port robotic operation with a robotic single-port access plus one wristed robotic
      arm for colon cancer was introduced to overcome the limitations of single-port
      laparoscopic rectal surgery. Aim: Single-port laparoscopic surgery has some
      advantages, including improved cosmetic outcomes and minimized parietal trauma.
      However, the pure single-port laparoscopic rectal cancer operation is
      challenging. Recently, a reduced-port robotic operation with a robotic single
      port access plus one wristed robotic arm for colon cancer was introduced to
      overcome the limitations of single-port laparoscopic rectal surgery. Material and
      methods: We performed a single-port plus an additional port robotic operation
      using a robotic single-port access through the umbilical incision, and the
      wristed robotic instruments were inserted through an additional robotic port in
      the right lower quadrant. Results: The total operative and docking times were 310
      min and 25 min, respectively. The total number of lymph nodes harvested was 12,
      and the proximal and distal resection margins were 11.1 and 2 cm, respectively.
      The patient was discharged on postoperative day 12 uneventfully. Conclusions:
      Based on a representative case, reduced-port robotic total mesorectal excision
      for rectal cancer using the single-port access appears to be feasible and safe.
      This approach could overcome the limitations of single-port laparoscopic rectal
      surgery.

PMID- 29362654
TI  - Transcatheter arterial embolization for upper gastrointestinal tract bleeding.
AB  - Introduction: Transcatheter arterial embolization is a possible treatment for
      patients with recurrent bleeding from the upper gastrointestinal tract after
      failed endoscopic management and is also an alternative to surgical treatment.
      Aim: To analyze the outcomes of transcatheter arterial embolization and identify
      the clinical and technical factors that influenced the rates of morbidity and
      mortality. Material and methods: A retrospective analysis was carried out, based
      on the data of 36 patients who underwent transcatheter arterial embolization for
      acute nonvariceal upper gastrointestinal bleeding in 2013 to 2015 in our center.
      An analysis was performed between early rebleeding rates, mortality and the
      following factors: patient sex, age, number of units of packed red blood cells
      and packed plasma administered to the patients, length of hospital stay,
      therapeutic or prophylactic embolization. Results: The technical success rate of
      the embolization procedure was 100%. There were 15 (41.70%) therapeutic
      embolizations and 21 (58.3%) prophylactic embolizations. There was a 77.8%
      clinical success rate. Following embolization, 10 (27.80%) patients had repeated
      bleeding and 9 (25.0%) patients died. Significant associations were found between
      rebleeding and prophylactic embolization (OR = 10.53; p = 0.04) and between
      mortality and prophylactic embolization (OR = 10.53; p = 0.04) and units of
      packed red blood cells (OR = 1.25; p < 0.01). Conclusions: In our experience,
      transcatheter arterial embolization is a safe treatment method for acute
      nonvariceal upper gastrointestinal bleeding and a possible alternative to surgery
      for high-risk patients.

PMID- 29362655
TI  - Percutaneous radiofrequency and microwave ablation in the treatment of renal
      tumors - 10 years of experience.
AB  - Introduction: The standard radical treatment of renal cell carcinoma is surgical
      resection, but it is not suitable for patients with serious medical comorbidities
      and solitary kidney tumors. Minimally invasive ablation techniques could be an
      appropriate therapeutic alternative. Aim: To retrospectively evaluate the
      technical success, mid-term and long-term efficacy and safety of radiofrequency
      and microwave ablation in patients with small renal tumors. Material and methods:
      Over the course of 10 years, 91 ablation procedures in 64 patients for 68 tumors,
      of size 12-60 mm, were performed using only conscious sedation. These ablations
      were done under the guidance of computed tomography. We treated 41 males and 23
      females with solitary kidney tumors (14 cases) and tumors in non-surgical
      candidates (54 cases). Results: In 50 (73.5%) tumors single treatment was
      successful; in 13 (19.1%) cases a second procedure was used successfully, and in
      the 5 largest tumors (sizes 45-60 mm, 7.4%) a third treatment was necessary.
      Within the follow-up 10 (15.6%) patients died, but none due to metastatic renal
      cell carcinoma. Only 1 serious complication was observed - retroperitoneal and
      psoatic hematoma. Early recurrence occurred in 18 (26.5%) tumors. Late recurrence
      was detected in 5 (7.4%) cases. In all cases complete local control of the renal
      tumors was reached. Conclusions: Percutaneous ablation is a very effective
      treatment for patients with small renal tumors of the T1a group with a minimal
      complication rate.

PMID- 29362656
TI  - Clinical efficacy and safety of transcatheter embolization for vascular
      complications after percutaneous nephrolithotomy.
AB  - Introduction: Percutaneous nephrolithotomy (PNL) is the preferred procedure for
      safe and effective surgical treatment of kidney stones. Hemorrhage is the most
      serious complication of PNL, resulting from pseudoaneurysm (PA) or arteriovenous
      fistula (AVF), and can usually be controlled with conservative treatment. Aim: To
      evaluate endovascular treatments and outcomes of vascular complications observed
      after PNL. Material and methods: We retrospectively reviewed data on 19 patients
      who underwent renal embolization due to post-PNL renal artery bleeding between
      March 2005 and September 2016. Embolization materials included embolization coils
      and glue. The incidence of post-PNL vascular complications and their endovascular
      treatments, outcomes, and the follow-up data were analyzed. Results: Nineteen
      (1.1%) of 1,609 patients (mean age: 44.9 years, range: 19-75 years) underwent
      angiography and subsequent transcatheter embolization to control bleeding. The
      mean time to onset of hemorrhage was 7.2 days after PNL (range: 3-18 days). The
      PNL entry site was the lower calyx in 15 patients, the middle calyx in 3, and the
      upper calyx in 1. PA, AVF, and PA plus AVF occurred in 14, 5, and 3 of the 19
      renal angiography patients, respectively. Embolization of the affected vessels
      was successful in all 19 patients. The embolization materials of coil, glue, and
      coil plus glue were used in 16, 3, and 2 patients, respectively. Conclusions:
      Severe hematuria is a rare complication of PNL and can be successfully treated
      with transcatheter embolization.

PMID- 29362657
TI  - Clinical evaluation of embolization of the superior vesical prostatic artery for
      treatment of benign prostatic hyperplasia: a single-center retrospective study.
AB  - Introduction: Non-surgical minimally invasive treatments are greatly needed for
      patients with symptomatic benign prostatic hyperplasia (BPH), for whom medical
      treatment has failed and surgery is contraindicated. This study retrospectively
      evaluated the efficacy and safety of super-selective prostatic artery
      embolization (PAE) for BPH, relative to transurethral resection of the prostate
      (TURP). Aim: To clinically evaluate the efficacy and safety of super-selective
      PAE for BPH, relative to TURP. Material and methods: From February 2012 to March
      2015, patients with BPH underwent selective PAE (n = 17) or TURP (control group;
      n = 40). Prostate volume, maximum urinary flow rate (Qmax), International
      Prostate Symptoms Score (IPSS), and quality of life (QoL) score were evaluated at
      baseline and postoperative 3, 6, and 12 months. Complications were also recorded.
      Results: All the procedures were technically successfully. At postoperative 1
      year, patients given PAE had significantly greater prostate volume (64.6 +/-10.2
      ml), IPSS (23.9 +/-4.9), and QoL (4.1 +/-0.7) compared with the control patients
      (42.0 +/-7.5 ml, 13.1 +/-3.5, and 2.1 +/-0.7, respectively). The Qmax of the PAE
      group (9.5 +/-3.7 ml/s) was significantly lower than that of the control (21.8 +/
      4.2 ml/s). The changes in parameters of the TURP patients relative to the
      preoperative baseline were significantly greater than those of the PAE group. No
      severe complications occurred. Conclusions: Prostatic artery embolization was
      demonstrated as safe and effective and may be considered an alternative treatment
      for BPH patients, especially for those who are not candidates for or refuse
      surgery.

PMID- 29362658
TI  - Spinal anesthesia is safe in laparoscopic total extraperitoneal inguinal hernia
      repair. A retrospective clinical trial.
AB  - Introduction: Laparoscopic total extraperitoneal (TEP) inguinal hernia repair is
      an effective and safe method for the treatment of inguinal hernia. There are very
      few studies on regional anesthesia methods in TEP surgery. Aim: To compare TEP
      inguinal hernia repair performed when the patient was treated under spinal
      anesthesia (SA) with that performed under general anesthesia (GA). Material and
      methods: All total of 80 patients were studied between December 2015 and March
      2017. Hyperbaric bupivacaine and fentanyl were used for SA, to achieve a
      sensorial level of T3. Propofol, sevoflurane, rocuronium, fentanyl, and tracheal
      intubation were used for GA. Intraoperative events related to SA, surgical times,
      intra- and postoperative complications, and pain scores were recorded. Results:
      The mean operative time in the SA TEP group was 70.2 +/-6.7 min, which was
      significantly longer than the mean operative time in the GA TEP group of 67.2 +/
      6.2 min (p < 0.038). The mean pain scores in the SA TEP group were 0.23 +/-0.42
      at the first hour, 1.83 +/-0.64 at 6 h and 1.28 +/-0.45 at 24 h. These scores
      were significantly lower than the corresponding scores of 5.18 +/-0.84 (p <
      0.001), 2.50 +/-0.55 (p < 0.001) and 1.58 +/-0.55 in the GA TEP group. Generally,
      patients were more satisfied with SA than GA (p < 0.004). Conclusions: Spinal
      anesthesia TEP is significantly less painful in the early postoperative period,
      leading to earlier ambulation than GA TEP. Additionally, SA TEP results in
      significantly less need for analgesics and better patient satisfaction results.
      SA TEP seems to be a better alternative than the existing GA TEP.

PMID- 29362659
TI  - Use of the blue cotton screen method with endoscopy to detect occult esophageal
      foreign bodies.
AB  - More than 20,000 cases of upper gastrointestinal foreign bodies (FBs) have been
      reported in the last 5 years in China. Early detection and treatment is vital in
      these patients. Differential diagnosis of esophageal injury and occult esophageal
      foreign bodies is challenging, particularly in the case of non-radio-opaque
      foreign bodies. A diagnostic technique with high accuracy and low risk is needed
      for clinical practice. We describe successful use of the "blue cotton screen
      method" to detect esophageal foreign bodies in 2 patients. The advantages and
      disadvantages of various diagnostic modalities in the management of patients with
      foreign body ingestion are presented. This technique is safer and more effective
      than traditional methods for foreign body impaction in the esophageal cavity. It
      could be applied for screening and in the differential diagnosis of esophageal
      injury and FBs in the esophageal lumen.

PMID- 29362661
TI  - Laparoscopy-assisted micropercutaneous choledocholithotripsy with holmium laser
      in a cholecystectomized patient: an initial report.
AB  - We present a novel minimally invasive technique, laparoscopy-assisted
      micropercutaneous choledocholithotripsy, for choledocholithiasis that cannot be
      treated with other endoscopic techniques. This technique includes standard
      laparoscopic exploration of the common bile duct, combined with an all-seeing
      needle and holmium laser lithotripsy. As is known, an all-seeing needle is used
      in micropercutaneous nephrolithotomy for middle-sized renal stones. In this
      technique, an all-seeing needle was inserted into the dilatated common bile duct
      under laparoscopic vision and then a lithotripsy procedure was performed with a
      holmium laser behind the biliary stent. A cholecystectomized female patient with
      a 21-mm stone in the common bile duct who previously underwent an unsuccessful
      endoscopic retrograde cholangiopancreatography procedure was operated on in our
      service with laparoscopy-assisted micropercutaneous choledocholithotomy without a
      T-tube. This novel procedure was completed uneventfully and the patient was
      discharged without any complications. In the future, this procedure will
      hopefully be a treatment modality in choledocholithiasis that cannot be treated
      by other minimally invasive techniques.

PMID- 29362660
TI  - Laparoscopic approach in the treatment of large leiomyoma of the lower third of
      the esophagus.
AB  - Leiomyoma of the lower third of the esophagus is a relatively rare disorder but
      the most common benign tumor of the esophagus. We present a case of an involuted
      esophageal leiomyoma, 11 cm in size, treated by the laparoscopic approach. The
      preoperative computed tomogram visualized a mass 3 * 1.5 cm in diameter in the
      lower esophagus without an eccentric lumen or compression of nearby organs.
      Resection of the tumor was indicated according to the patient's symptoms and to
      exclude malignancy. Laparoscopic enucleation of esophageal leiomyoma was
      performed. The overall operative time was 205 min. The diagnosis of leiomyoma was
      established on histopathology and immunohistochemistry staining. The patient
      resumed the intake of a normal diet on the 5th postoperative day and was
      discharged from hospital 8 days after the surgery. We have found this minimally
      invasive operation to be an effective and well-tolerated treatment option,
      determined by the experience of the surgeon.

PMID- 29362662
TI  - Evaluation of pain relief sufficiency using the Cumulative Analgesic Consumption
      Score (CACS) and its modification (MACS).
AB  - Postoperative pain is one of the major complications in general and bariatric
      surgery, associated with ongoing problems such as ileus, pneumonia and prolonged
      mobilization. In this study, patients undergoing bariatric surgery were analyzed
      according to their postoperative pain relief regime. In one group patients were
      treated with a patient-controlled analgesia (PCA) device, while the other group
      was treated with oral and intravenous analgesic medication. The aim of this study
      was to analyze which postoperative pain relief therapy would be more appropriate.
      We chose the Cumulative Analgesic Consumption Score (CACS) and Numeric Rating
      Scale (NRS) for pain measurement. For better comparison, we performed a
      modification of CACS according to PCA treatment. We observed better pain relief
      in the PCA group. Furthermore, we observed an advantage of treatment with
      laxatives in patients treated with PCA. In conclusion, PCA devices are
      appropriate instruments for postoperative pain relief in bariatric patients. CACS
      is a practical tool for postoperative pain measurement, describing individual
      pain sensation more objectively, although holding further potential in
      modification.

PMID- 29362663
TI  - Laparoscopy in small bowel obstruction - current status - review.
AB  - Introduction: Acute small bowel obstruction (SBO) is an urgent medical condition.
      Its diagnosis is based mainly on a clinical examination followed by confirmatory
      simple routine radiological examinations such as plain X-ray of the abdominal
      cavity or computed tomography (CT). However, a real surgical challenge is not a
      decision whether to perform a surgery, but a decision when and how to perform it.
      Aim: To determine the place of laparoscopy in contemporary management of acute
      SBO based on the current literature. Material and methods: A review of the
      literature based on the Medline database and including mainly the period of 2013
      2017 was performed. Conclusions: With regard to SBO, laparoscopy is a technique
      showing its advantages resulting from a minimally invasive approach. However, SBO
      is still a condition where the use of laparoscopy is limited mainly to selected
      cases such as SBO caused by single adhesions or foreign bodies. A basic
      limitation of using this technique is advanced and complicated SBO and lack of
      sufficient technical skills of the surgeon.

PMID- 29362664
TI  - Postprocessing Algorithm for Driving Conventional Scanning Tunneling Microscope
      at Fast Scan Rates.
AB  - We present an image postprocessing framework for Scanning Tunneling Microscope
      (STM) to reduce the strong spurious oscillations and scan line noise at fast scan
      rates and preserve the features, allowing an order of magnitude increase in the
      scan rate without upgrading the hardware. The proposed method consists of two
      steps for large scale images and four steps for atomic scale images. For large
      scale images, we first apply for each line an image registration method to align
      the forward and backward scans of the same line. In the second step we apply a
      "rubber band" model which is solved by a novel Constrained Adaptive and Iterative
      Filtering Algorithm (CIAFA). The numerical results on measurement from
      copper(111) surface indicate the processed images are comparable in accuracy to
      data obtained with a slow scan rate, but are free of the scan drift error
      commonly seen in slow scan data. For atomic scale images, an additional first
      step to remove line-by-line strong background fluctuations and a fourth step of
      replacing the postprocessed image by its ranking map as the final atomic
      resolution image are required. The resulting image restores the lattice image
      that is nearly undetectable in the original fast scan data.

PMID- 29362665
TI  - Effect of Vitamin D Receptor Activation on the AGE/RAGE System and
      Myeloperoxidase in Chronic Kidney Disease Patients.
AB  - Vitamin D receptor (VDR) activation has been reported to increase circulating
      levels of the advanced glycation end products (AGE) and their decoy receptor
      (RAGE). However, until now, the effect of VDR activation on AGE and RAGE has not
      been tested in the setting of a randomized, double-blind clinical trial. We have
      therefore analyzed the effect of VDR activation by paricalcitol on pentosidine,
      S100A12/ENRAGE, and RAGE and on established biomarkers of oxidative stress like
      myeloperoxidase in CKD patients in the PENNY trial. At baseline, human
      S100A12/ENRAGE, RAGE, and myeloperoxidase, but not pentosidine, were
      intercorrelated, and the association between S100A12/ENRAGE and myeloperoxidase
      (r = 0.71, P < 0.001) was the strongest among these correlations. Paricalcitol
      failed to modify biomarkers of the AGE/RAGE system and myeloperoxidase in
      unadjusted and adjusted analyses by the generalized linear model (GLM). No effect
      modification by other risk factors was registered. Paricalcitol does not modify
      biomarkers of the AGE/RAGE system and myeloperoxidase in CKD patients. The
      apparent increase in RAGE levels by VDR activation reported in previous
      uncontrolled studies is most likely due to confounding factors rather than to VDR
      activation per se. This trial is registered with NCT01680198.

PMID- 29362666
TI  - Active Fragment of Veronica ciliata Fisch. Attenuates t-BHP-Induced Oxidative
      Stress Injury in HepG2 Cells through Antioxidant and Antiapoptosis Activities.
AB  - Excessive amounts of reactive oxygen species (ROS) in the body are a key factor
      in the development of hepatopathies such as hepatitis. The aim of this study was
      to assess the antioxidation effect in vitro and hepatoprotective activity of the
      active fragment of Veronica ciliata Fisch. (VCAF). Antioxidant assays (DPPH,
      superoxide, and hydroxyl radicals scavenging) were conducted, and
      hepatoprotective effects through the application of tert-butyl hydroperoxide- (t
      BHP-) induced oxidative stress injury in HepG2 cells were evaluated. VCAF had
      high phenolic and flavonoid contents and strong antioxidant activity. From the
      perspective of hepatoprotection, VCAF exhibited a significant protective effect
      on t-BHP-induced HepG2 cell injury, as indicated by reductions in cytotoxicity
      and the levels of ROS, 8-hydroxydeoxyguanosine (8-OHdG), and protein carbonyls.
      Further study demonstrated that VCAF attenuated the apoptosis of t-BHP-treated
      HepG2 cells by suppressing the activation of caspase-3 and caspase-8. Moreover,
      it significantly decreased the levels of ALT and AST, increased the activities of
      acetyl cholinesterase (AChE), glutathione (GSH), superoxide dismutase (SOD), and
      catalase (CAT), and increased total antioxidative capability (T-AOC).
      Collectively, we concluded that VCAF may be a considerable candidate for
      protecting against liver injury owing to its excellent antioxidant and
      antiapoptosis properties.

PMID- 29362667
TI  - Xylopine Induces Oxidative Stress and Causes G2/M Phase Arrest, Triggering
      Caspase-Mediated Apoptosis by p53-Independent Pathway in HCT116 Cells.
AB  - Xylopine is an aporphine alkaloid that has cytotoxic activity to cancer cells. In
      this study, the underlying mechanism of xylopine cytotoxicity was assessed in
      human colon carcinoma HCT116 cells. Xylopine displayed potent cytotoxicity in
      different cancer cell lines in monolayer cultures and in a 3D model of cancer
      multicellular spheroids formed from HCT116 cells. Typical morphology of
      apoptosis, cell cycle arrest in the G2/M phase, increased internucleosomal DNA
      fragmentation, loss of the mitochondrial transmembrane potential, and increased
      phosphatidylserine externalization and caspase-3 activation were observed in
      xylopine-treated HCT116 cells. Moreover, pretreatment with a caspase-3 inhibitor
      (Z-DEVD-FMK), but not with a p53 inhibitor (cyclic pifithrin-alpha), reduced
      xylopine-induced apoptosis, indicating induction of caspase-mediated apoptosis by
      the p53-independent pathway. Treatment with xylopine also caused an increase in
      the production of reactive oxygen/nitrogen species (ROS/RNS), including hydrogen
      peroxide and nitric oxide, but not superoxide anion, and reduced glutathione
      levels were decreased in xylopine-treated HCT116 cells. Application of the
      antioxidant N-acetylcysteine reduced the ROS levels and xylopine-induced
      apoptosis, indicating activation of ROS-mediated apoptosis pathway. In
      conclusion, xylopine has potent cytotoxicity to different cancer cell lines and
      is able to induce oxidative stress and G2/M phase arrest, triggering caspase
      mediated apoptosis by the p53-independent pathway in HCT116 cells.

PMID- 29362668
TI  - Advances in cytogenetics of Brazilian rodents: cytotaxonomy, chromosome evolution
      and new karyotypic data.
AB  - Rodents constitute one of the most diversified mammalian orders. Due to the
      morphological similarity in many of the groups, their taxonomy is controversial.
      Karyotype information proved to be an important tool for distinguishing some
      species because some of them are species-specific. Additionally, rodents can be
      an excellent model for chromosome evolution studies since many rearrangements
      have been described in this group.This work brings a review of cytogenetic data
      of Brazilian rodents, with information about diploid and fundamental numbers,
      polymorphisms, and geographical distribution. We point out that, even with the
      recent efforts on cytogenetic studies in this group, many species lack karyotypic
      data. Moreover, we describe for the first time the karyotype of Carterodon
      sulcidens (Lund, 1838) (Family Echimyidae), a new fundamental number for an
      undescribed species of Neacomys Thomas, 1900 (Family Cricetidae, Subfamily
      Sigmodontinae), and illustrate the karyotype of a Brazilian specimen of Mus
      musculus Linnaeus, 1758 (Family Muridae). This review compiles the cytogenetic
      data on Brazilian rodents reported in the last three decades, after the last
      revision published in 1984, including synonyms, chromosomal variations, and
      geographic distribution. Additionally, it also reinforces that Brazilian
      biodiversity is still poorly known, considering the new data reported here.

PMID- 29362669
TI  - Studies in two allopatric populations of Hypostomus affinis (Steindachner, 1877):
      the role of mapping the ribosomal genes to understand the chromosome evolution of
      the group.
AB  - Several cytogenetic markers show chromosomal diversity in the fish such as
      "armoured catfish". Although studies have characterized many species in the major
      genera representing these Siluridae, particularly in the genus Hypostomus
      Lacepede, 1803, trends in chromosome evolution of this group remain unclear. The
      Paraiba do Sul river basin contains the armoured catfish Hypostomus affinis
      Steindachner, 1877, which is unique because of its distribution of repetitive
      DNAs, the 5S and 18S rDNA. Identified samples and registered collections in
      Brazilian museums were identified as the same typological species, while we
      observed wide variations in the physical location of this gene in the karyotype
      based on fluorescent in situ hybridization results. In this study, we propose
      that these species can represent evolutionarily independent units, as these fish
      frequently undergo processes such as dispersion and vicariance and that the rDNA
      is associated with DNA that spreads in the genome, such as transposons.
      Additionally, the absence of gene flow due to the distance of the sample location
      could intensify evolutionary processes. The phenotypes found for the 18S rDNA
      showed minor changes in relation to the number of sites between the lower and
      upper drainage regions of Paraiba do Sul. The large difference in the number of
      sites found for the 5S rDNA entered the same region (upper drainage of the basin)
      and the literature data could represent a population dynamics where an expansion
      of the 5S rDNA sites provides an extinct or non-sampled cytotype in this work.

PMID- 29362670
TI  - Molecular phylogenetic reconstruction and localization of the (TTAGG)n telomeric
      repeats in the chromosomes of Acromyrmex striatus (Roger, 1863) suggests a lower
      ancestral karyotype for leafcutter ants (Hymenoptera).
AB  - Chromosome counts and karyotype characterization have proved to be important
      features of a genome. Chromosome changes during the diversification of ants might
      play an important role, given the diversity and success of Formicidae.
      Comparative karyotype analyses on ants have enriched and helped ant systematics.
      Among leafcutter ants, two major chromosome counts have been described, one
      frequent in Atta Fabricius, 1804 (2n = 22 in all Atta spp. whose karyotype is
      known) and the other frequent in Acromyrmex Mayr, 1865 (2n = 38 in the majority
      of species whose karyotype is known). The main exception is Acromyrmex striatus
      (Roger, 1863), which harbors a diploid chromosome set of 22. Here we describe the
      use of fluorescence in situ hybridization (FISH) with telomeric probes with
      (TTAGG)6 repeats to describe the telomere composition of A. striatus and to
      recover potential interstitial non-telomeric signals that may reflect fusion
      events during the evolution of leafcutter lineage from 38 to 22 chromosomes.
      Further, we reconstruct the ancestral chromosome numbers of the leafcutter clade
      based on a recently proposed molecular phylogenetic hypothesis and phylogenomic
      tree. Distinct signals have been observed in both extremities on the telomere
      chromosomes of A. striatus. Non-telomeric signals have not been retrieved in our
      analysis. It could be supposed that the low-numbered karyotype indeed represents
      the ancestral chromosome number of leafcutters. The phylogenetic reconstruction
      also recovered a low chromosome number from the diverse approaches implemented,
      suggesting that n = 11 is the most likely ancestral karyotype of the leafcutter
      ants and is a plesiomorphic feature shared between A. striatus and Atta spp.

PMID- 29362671
TI  - The global origins of resistance-associated variants in the non-structural
      proteins 5A and 5B of the hepatitis C virus.
AB  - New, costly, fast acting, therapies targeting the non-structural proteins 5A and
      5B (NS5A and NS5B) regions of the hepatitis C virus (HCV) genome are curative in
      the majority of cases. Variants with certain mutations in the NS5A and NS5B
      regions of HCV have been shown to reduce susceptibility to direct-acting NS5A and
      NS5B therapy and are found in treatment naive patients. Despite this, the ease
      with which these variants evolve is poorly known, as are their evolutionary and
      geographic origins. To address this crucial gap we inferred the evolutionary and
      geographic origins of resistance-associated variants (RAVs) in the HCV NS5A and
      NS5B regions of subtypes 1a, 1b, and 3a sequences available from global
      databases. We found that RAVs in the NS5A region of HCV, when prevalent, were
      widely dispersed throughout the phylogenetic tree of HCV with multiple
      independent origins and that these variants are globally distributed. In
      contrast, most of the NS5B C316N variants came from one of two clades in the
      phylogenetic tree of HCV subtype 1b. The presence of serine (S) at codon 218 of
      HCV NS5B appears to facilitate the evolution of the C316N RAV. Other NS5B RAVs
      did not arise very frequently in our data set, except for S556G in subtype 1b and
      with respect to geography NS5B RAVs were also globally distributed. The inferred
      distribution of RAVs in the NS5A region and frequency of their origin suggest a
      low fitness barrier without the need for co-evolution of compensatory mutations.
      A low fitness barrier may allow rapid selection of de novo resistance to NS5A
      inhibitors during therapy.

PMID- 29362673
TI  - Challenges in Assessing Outcomes among Infants of Pregnant HIV-Positive Women
      Receiving ART in Uganda.
AB  - Since 2012, the WHO recommends lifelong ART with TDF+FTC/3TC+EFV for all HIV
      positive pregnant and breastfeeding women (Option B-plus). In this analysis we
      describe the proportion of early and late transmission in mothers with high
      retention in Kampala, Uganda. We included 700 pregnant women from January 2012 to
      August 2014 with a follow-up extended to August 2016; the median age was 31 years
      (IQR: 26-35), 36.3% in WHO stage 3/4; median CD4 count was 447 cells/MUL (IQR:
      301-651) and 73.3% were already on ART for a median time of 28 (IQR: 10-57)
      months; 52% infants were male and median weight was 3.2 Kg (IQR: 2.5-3.5). Five
      hundred and sixty-five (80.7%) infants had at least one test for HIV; 22 (3.1%)
      infants died, all with unknown serostatus; 3 tested positive at week 6 and one
      additional at months 12 and 18. Two of the mothers of the 4 HIV-positive infants
      were ART-naive at the time of pregnancy. We report very low documented HIV
      transmission comparable with those reported in clinical trials settings; however,
      demonstrating the efficacy of Option B-plus in terms of averted transmission in
      routine settings is challenging since high proportion of infants do not have
      documented HIV tests.

PMID- 29362672
TI  - Frequency of Toxocariasis among Patients Clinically Suspected to Have Visceral
      Toxocariasis: A Retrospective Descriptive Study in Sri Lanka.
AB  - Introduction: Human toxocariasis is caused by several species of the nematode
      Toxocara. Two common clinical syndromes are ocular and visceral larva migrans.
      Objectives: To determine the Toxocara antibody positivity in clinically suspected
      VLM patients and to describe demographic factors and clinical manifestations of
      seropositive patients. Methods: 522 clinically suspected patients were studied
      between 1993 and 2014. Relevant data was gathered from referral letters. Serum
      samples were subjected to Toxocara antigen ELISA. Results: Overall,
      seropositivity was 50.2% (262), of which 109 (40.8%) were positive at high level
      of Toxocara antibody carriage and 153 (58.4%) were positive at low levels. The
      seropositives ranged from 3 months to 70 years (mean = 7.8). Younger age group
      had higher levels of seropositivity and it was statistically significant.
      Majority of children under 5 years were seropositive (47.7%, n = 125).
      Seropositivity was common in males (55.3%, n = 145). Clinical manifestations of
      seropositives include lymphadenopathy (24.1%) skin rash (22.5%), dyspnoea
      (21.7%), fever (21%), hepatosplenomegaly (9.2%), and abdominal pain (3.8%). 197
      (75.2%) seropositive cases had eosinophilia. These symptoms were not
      statistically significant. Conclusions: This study confirms toxocariasis as an
      important cause of childhood ill health identifying common clinical symptoms
      recommending preventive measures to limit transmission.

PMID- 29362674
TI  - Robot-Assisted Hybrid Esophagectomy Is Associated with a Shorter Length of Stay
      Compared to Conventional Transthoracic Esophagectomy: A Retrospective Study.
AB  - Aim: To compare the peri- and postoperative data between a hybrid minimally
      invasive esophagectomy (HMIE) and the conventional Ivor Lewis esophagectomy.
      Methods: Retrospective comparison of perioperative characteristics, postoperative
      complications, and survival between HMIE and Ivor Lewis esophagectomy. Results:
      216 patients were included, with 160 procedures performed with the conventional
      and 56 with the HMIE approach. Lower perioperative blood loss was found in the
      HMIE group (600 ml versus 200 ml, p < 0.001). Also, a higher median number of
      lymph nodes were harvested in the HMIE group (median 28) than in the conventional
      group (median 23) (p = 0.002). The median length of stay was longer in the
      conventional group compared to the HMIE group (11.5 days versus 10.0 days, p =
      0.03). Patients in the HMIE group experienced fewer grade 2 or higher
      complications than the conventional group (39% versus 57%, p = 0.03). The rate of
      all pulmonary (51% versus 43%, p = 0.32) and severe pulmonary complications (38%
      versus 18%, p = 0.23) was not statistically different between the groups.
      Conclusions: The HMIE was associated with lower intraoperative blood loss, a
      higher lymph node harvest, and a shorter hospital stay. However, the inborn
      limitations with the retrospective design stress a need for prospective
      randomized studies. Registration number is DRKS00013023.

PMID- 29362675
TI  - Are Shopkeepers Suffering from Pulmonary Tuberculosis in Bahir Dar City,
      Northwest Ethiopia: A Cross-Sectional Survey.
AB  - Background: Despite several interventions, tuberculosis (TB) continues to be a
      major public health concern in developing countries. Objective: To determine
      pulmonary TB prevalence and associated factors among shopkeepers in Bahir Dar
      City, Ethiopia. Methods: A cross-sectional study was conducted in 2016 among 520
      shopkeepers who had TB signs and symptoms using questionnaire interview and
      sputum samples processing. Shopkeepers were considered TB positive if two sputum
      slides became positive. Data were edited and analyzed using SPSS version 23.
      Multivariable logistic regression analysis was used to identify factors. Results:
      A total of 520 shopkeepers were interviewed and gave sputum samples. About 256
      (49.2%) of them were under the <=30 years' age category, 22.0% can read and
      write, 65.0% were Muslims, and 32.0% originated from rural areas. Pulmonary TB
      prevalence was 7.0% (37/520), and positivity proportion was 57.0% (21/37) in
      males and 70.0% (26/37) in urban residents. Smaller (44.0%) shopkeepers got
      health education on TB. Illiteracy, no health education, contact history,
      cigarette smoking, nonventilated shops, and comorbidities were factors to TB
      infection (p value < 0.05). Conclusions: Significant numbers of shopkeepers were
      infected by TB. Factors to TB infection were either personal or related to
      comorbidities or the environment. Therefore, TB officials need to specially
      emphasize awareness creation, occupational health, and early screening to prevent
      TB.

PMID- 29362676
TI  - Design, Synthesis, and Cytotoxicity Evaluation of Novel Griseofulvin Analogues
      with Improved Water Solubility.
AB  - Griseofulvin 1 is an important antifungal agent that has recently received
      attention due to its antiproliferative activity in mammalian cancer cells. Study
      of SAR of some griseofulvin analogues has led to the identification of 2'
      benzyloxy griseofulvin 3, a more potent analogue which retards tumor growth
      through inhibition of centrosomal clustering. However, similar to griseofulvin 1,
      compound 3 exhibited poor aqueous solubility. In order to improve the poor water
      solubility, six new griseofulvin analogues 5-10 were synthesized and tested for
      their antiproliferative activity and water solubility. The semicarbazone 9 and
      aminoguanidine 10 analogues were the most potent against HCT116 and MCF-7 cell
      lines. In combination studies, compound 9 was found to exert synergistic effects
      with tamoxifen and 5-fluorouracil against MCF-7 and HCT116 cells proliferation,
      respectively. The flow cytometric analysis of effect of 9 on cell cycle
      progression revealed G2/M arrest in HCT116. In addition, compound 9 induced
      apoptosis in MCF-7 cells. Finally, all synthesized analogues revealed higher
      water solubility than griseofulvin 1 and benzyloxy analogue 3 in pH 1.2 and 6.8
      buffer solutions.

PMID- 29362677
TI  - Frequency of c.35delG Mutation in GJB2 Gene (Connexin 26) in Syrian Patients with
      Nonsyndromic Hearing Impairment.
AB  - Background: Hearing impairments (HI) are the most common birth defect worldwide.
      Very large numbers of genes have been identified but the most profound is GJB2.
      The clinical interest regarding this gene is very pronounced due to its high
      carrier frequency (0.5-5.4%) across different ethnic groups. This study aimed to
      determine the prevalence of common GJB2 mutations in Syrian patients with
      profound sensorineural HI. Methods: We carried out PCR, restriction enzyme based
      screening, and sequencing of 132 Syrian patients diagnosed clinically with
      hereditary deafness for different GJB2 mutations. Results: The result revealed
      that, in GJB2 gene, c.35delG is the most prevalent among affected studied
      subjects (13.64%), followed by c.457G>A (2.4%). Conclusion: The benefit of this
      study on the one hand is its first report of prelingual deafness causative gene
      mutations identified by sequencing technology in the Syrian families. It is
      obvious from the results that the deployment in biomedical research is highly
      effective and has a great impact on the ability to uncover the cause of genetic
      variation in different genetic diseases.

PMID- 29362679
TI  - Bone Lid Technique Using a Piezoelectric Device for the Treatment of a Mandibular
      Bony Lesion.
AB  - Different techniques for the enucleation of jaw cyst lesion in the oral and
      maxillofacial regions have been proposed, including the bone lid technique. The
      purpose of this case report is to describe the case of a cystic lesion,
      approached with the bone lid technique performed using a piezoelectric device,
      with an 8-month clinical and radiographic follow-up. A 14-year-old male patient
      was treated for a suspicious lesion detected on a panoramic radiograph. The
      concerned area was surgically accessed, and a radiographically predetermined bony
      window was drawn, and the beveled bony lid was removed. The underlying lesion was
      enucleated and sent for pathology as a routine procedure, and the removed bony
      lid was repositioned in situ and secured with a collagen tape. Healing was
      uneventful with limited swelling and reduced pain. A complete radiographic bone
      healing at the previously diseased site was confirmed with an 8-month cone beam
      computed tomography (CBCT) scan with no buccal bone resorption nor ridge
      collapse. The bone lid technique with a piezoelectric device was noninvasive and
      atraumatic in this case. Further studies are needed and could lead to the
      adaptation of this approach as a possible standard of care.

PMID- 29362678
TI  - Long-Term High Salt Intake Involves Reduced SK Currents and Increased
      Excitability of PVN Neurons with Projections to the Rostral Ventrolateral Medulla
      in Rats.
AB  - Evidence indicates that high salt (HS) intake activates presympathetic
      paraventricular nucleus (PVN) neurons, which contributes to sympathoexcitation of
      salt-sensitive hypertension. The present study determined whether 5 weeks of HS
      (2% NaCl) intake alters the small conductance Ca2+-activated potassium channel
      (SK) current in presympathetic PVN neurons and whether this change affects the
      neuronal excitability. In whole-cell voltage-clamp recordings, HS-treated rats
      had significantly decreased SK currents compared to rats with normal salt (NS,
      0.4% NaCl) intake in PVN neurons. The sensitivity of PVN neuronal excitability in
      response to current injections was greater in HS group compared to NS controls.
      The SK channel blocker apamin augmented the neuronal excitability in both groups
      but had less effect on the sensitivity of the neuronal excitability in HS group
      compared to NS controls. In the HS group, the interspike interval (ISI) was
      significantly shorter than that in NS controls. Apamin significantly shortened
      the ISI in NS controls but had less effect in the HS group. This data suggests
      that HS intake reduces SK currents, which contributes to increased PVN neuronal
      excitability at least in part through a decrease in spike frequency adaptation
      and may be a precursor to the development of salt-sensitive hypertension.

PMID- 29362680
TI  - Impacted Metallic Spring Requiring Cervical Esophagotomy: A Case Report and
      Review of the Literature on Foreign Body Removal.
AB  - Foreign body ingestion is a commonly encountered problem and can cause
      significant morbidity and mortality. When removal of a foreign body from the
      upper gastrointestinal tract is indicated, endoscopy is the modality of choice
      and has a high reported success rate. However, in less than 1% of cases,
      endoscopic removal of a foreign body is unsuccessful and surgical intervention is
      necessary. We report a unique case of a large, sharp metallic spring swallowed by
      an incarcerated patient which subsequently became lodged in his upper thoracic
      esophagus. This spring was unable to be removed endoscopically due to risk of
      perforation and cervical esophagotomy was needed for its successful removal,
      illustrating the limitations of endoscopic techniques in removal of foreign
      bodies and the role surgical intervention has in these rare instances.

PMID- 29362681
TI  - Unusual Radiographic Presentation of Pneumocystis Pneumonia in a Patient with
      AIDS.
AB  - Pneumocystis jirovecii pneumonia (PCP) typically presents as an interstitial and
      alveolar process with ground glass opacities on chest computed tomography (CT).
      The absence of ground glass opacities on chest CT is thought to have a high
      negative predictive value for PCP in individuals with AIDS. Here, we report a
      case of PCP in a man with AIDS who presented to our hospital with subacute
      shortness of breath and a nonproductive cough. While his chest CT revealed
      diffuse nodular rather than ground glass opacities, bronchoscopy with
      bronchoalveolar lavage and transbronchial biopsies confirmed the diagnosis of PCP
      and did not identify additional pathogens. PCP was not the expected diagnosis
      based on chest CT, but it otherwise fit well with the patient's clinical and
      laboratory presentation. In the era of combination antiretroviral therapy,
      routine prophylaxis for PCP, and increased use of computed tomography, it may be
      that PCP will increasingly present with nonclassical chest radiographic patterns.
      Clinicians should be aware of this presentation when selecting diagnostic and
      management strategies.

PMID- 29362682
TI  - Obturator Nerve Schwannoma as a Mimic of Ovarian Malignancy.
AB  - The obturator nerve is an extremely rare location for schwannomas to originate,
      and such diagnosis is typically not considered among the imaging diagnostic
      possibilities for a cystic-solid pelvic mass. A 63-year-old female with a known
      pelvic mass presented with increasing pelvic pain. The mass, which had been
      followed by serial imaging over five years, was described showing mixed solid and
      cystic components, likely arising from the left ovary. Although the key diagnosis
      to be excluded was a primary ovarian malignancy, the patient chose to pursue
      active surveillance. Over the five years of close observation, the lesion
      increased slowly, while her CA-125 level showed no significant elevation.
      Increase in size of the mass and worsening pain and concern for a gynecologic
      malignancy on MRI led her to ultimately consent to a hysterectomy with bilateral
      salpingooophorectomy. During the surgery, the mass was noted to be contiguous
      with the left obturator nerve. Pathologic evaluation revealed a schwannoma (WHO
      grade I). The patient's postsurgical course was uneventful, without residual
      weakness in the left adductor muscles.

PMID- 29362683
TI  - A Rare Case of Metastatic Choriocarcinoma of Lung Origin.
AB  - Choriocarcinoma is part of the spectrum of gestational trophoblastic disease that
      occurs in women of reproductive age. Although the most common metastatic site of
      choriocarcinoma is the lung, primary pulmonary choriocarcinoma is rare. To
      diagnose primary pulmonary choriocarcinoma, the patient should have no previous
      gynecologic malignancy, have elevated human chorionic gonadotropin, and have
      pathological confirmation of the disease excluding gonadal primary site of the
      tumor. Due to the paucity of data, there are no guidelines for treatment.
      Prognosis of this malignancy is extremely poor. We report a rare case of
      metastatic primary lung choriocarcinoma in a 69-year-old postmenopausal woman who
      was treated with combination of surgery, chemotherapy, and radiation. The patient
      had a good outcome and is doing well after 1-year follow-up.

PMID- 29362684
TI  - Left Paraduodenal Hernia: A Rare Complication following Laparoscopic
      Appendectomy.
AB  - Paraduodenal hernias are rare congenital internal hernias accounting for <2% of
      intestinal obstruction. Left paraduodenal hernias (LPDHs) into the fossa of
      Landzert are the more common type and result from abnormal rotation of the midgut
      and failure of peritoneal fusion. Sequelae of these hernias usually occur
      spontaneously in the 4th or 5th decade of life and are more common in males and
      have a significant risk of incarceration and subsequent strangulation. We
      describe a case of a 15-year-old female who develops a LPDH following
      laparoscopic appendectomy, resulting in jejunal incarceration and subsequent
      small intestinal obstruction. The patient discussed is from an atypical
      demographic, being young and female. In addition, the precipitating event
      prompting incarceration of the hernia appears to be the application of
      pneumoperitoneum, placement in the Trendelenburg position, and manipulation of
      small intestine for the purpose of facilitating laparoscopic appendectomy. To our
      knowledge, this is the first reported case of LPDH exacerbated by laparoscopic
      procedure.

PMID- 29362685
TI  - Sustained Effectiveness of a Fixed-Dose Combination of Artesunate and Amodiaquine
      in 480 Patients with Uncomplicated Plasmodium falciparum Malaria in Cote
      d'Ivoire.
AB  - The objective of this study was to monitor the effectiveness of artesunate
      amodiaquine fixed-dose combination tablets (ASAQ Winthrop(r)) in the treatment of
      uncomplicated Plasmodium falciparum malaria in Cote d'Ivoire. Two enrolment
      periods (November 2009 to May 2010 and March to October 2013) were compared using
      an identical design. Subjects with proven monospecific P. falciparum infection
      according to the WHO diagnostic criteria were eligible. 290 patients during each
      period received a dose of ASAQ Winthrop tablets appropriate for their age. The
      primary outcome measure was PCR-corrected adequate clinical and parasitological
      response at Day 28 in the per protocol population (255 in Period 1 and 240 in
      Period 2). This was achieved by 95.7% of patients during Period 1 and 96.3%
      during Period 2. Over 95% of patients were afebrile at Day 3 and complete
      parasite clearance was achieved at Day 3 in >99% of patients. Nineteen adverse
      events in nineteen patients were considered as possibly related to treatment,
      principally vomiting, abnormal liver function tests, and pruritus. There was no
      evidence for loss of effectiveness over the three-year period in spite of strong
      drug pressure. This trial was registered in the US Clinical Trials Registry
      (clinical.trials.gov) under the identifier number NCT01023399.

PMID- 29362686
TI  - A Possible Link Between Pyriproxyfen and Microcephaly.
AB  - The Zika virus has been the primary suspect in the large increase in incidence of
      microcephaly in 2015-6 in Brazil. While evidence for Zika being the cause of some
      of the cases is strong, its role as the primary cause of the large number of
      cases in Brazil has not been confirmed. Recently, the disparity between the
      incidences in different geographic locations has led to questions about the
      virus's role. Here we consider the alternative possibility that the use of the
      insecticide pyriproxyfen for control of mosquito populations in Brazilian
      drinking water is the primary cause. Pyriproxifen is a juvenile hormone analog
      which has been shown to correspond in mammals to a number of fat soluble
      regulatory molecules including retinoic acid, a metabolite of vitamin A, with
      which it has cross-reactivity and whose application during development has been
      shown to cause microcephaly. Methoprene, another juvenile hormone analog that was
      approved as an insecticide based upon tests performed in the 1970s, has
      metabolites that bind to the mammalian retinoid X receptor, and has been shown to
      cause developmental disorders in mammals. Isotretinoin is another example of a
      retinoid causing microcephaly in human babies via maternal exposure and
      activation of the retinoid X receptor in developing fetuses. Moreover, tests of
      pyriproxyfen by the manufacturer, Sumitomo, widely quoted as giving no evidence
      for developmental toxicity, actually found some evidence for such an effect,
      including low brain mass and arhinencephaly-incomplete formation of the anterior
      cerebral hemispheres-in exposed rat pups. Finally, the pyriproxyfen use in Brazil
      is unprecedented-it has never before been applied to a water supply on such a
      scale. Claims that it is not being used in Recife, the epicenter of microcephaly
      cases, do not distinguish the metropolitan area of Recife, where it is widely
      used, and the municipality, and have not been adequately confirmed. Given this
      combination of information about molecular mechanisms and toxicological evidence,
      we strongly recommend that the use of pyriproxyfen in Brazil be suspended until
      the potential causal link to microcephaly is investigated further.

PMID- 29362687
TI  - False Low-Risk Single Nucleotide Polymorphism-Based Noninvasive Prenatal
      Screening in Pentasomy 49,XXXXY.
AB  - Introduction  Pentasomy 49,XXXXY is a sex chromosome anomaly difficult to be
      diagnosed prenatally. We describe a patient of pentasomy 49,XXXXY with false low
      risk results using a noninvasive prenatal screening (NIPS). A 30-year-old G1P0
      woman presented at 33 6/7 weeks, secondary to sonographic fetal anomalies. She
      had low-risk NIPS at 13 6/7 weeks. Anatomy survey showed bilateral clubfeet,
      clinodactyly of the left fifth digit, micropenis, and echogenic bowel.
      Cytogenetics analysis revealed pentasomy 49,XXXXY syndrome. We report third
      trimester sonographic features of a fetus with pentasomy 49,XXXXY and the
      importance of thorough pre- and posttest counseling for NIPS.

PMID- 29362688
TI  - Pregnant Women's Knowledge and Beliefs about the Safety and Outcomes of Delivery
      at Various Gestational Ages.
AB  - Objectives  Despite the morbidity associated with late preterm and early-term
      births, there is limited data on pregnant women's perception of neonatal risk
      based on gestational age (GA). Therefore, our objective was to determine pregnant
      women's perception of neonatal risks at varying GAs. Method  Through an anonymous
      24-question survey, pregnant women were asked to designate the GA at delivery
      that is desirable, safe, and defined as full term. Responses were compared based
      on race, history of preterm birth, and medical comorbidities. Results  Among the
      233 survey respondents, the majority (62.9%) desired delivery at 36 to 39 weeks'
      gestation. Black women were more likely to desire delivery at 28 to 35 weeks
      compared with other racial/ethnic groups ( p  = 0.005). Women with a history of
      preterm birth or medical complications were less likely to desire delivery at 40
      weeks. More than 40% of respondents thought delivery at 8 months of pregnancy was
      safe and 40.3% responded that 37 weeks' gestation is considered term. Conclusion 
      Misconceptions surrounding the definition of a term pregnancy are pervasive and
      vary by race, obstetric history, and medical comorbidities. Our findings
      highlight the need for patient education about appropriate gestational length,
      especially in minority and high-risk populations.

PMID- 29362689
TI  - Ergonomic risk and preventive measures of musculoskeletal disorders in the
      dentistry environment: an umbrella review.
AB  - Introduction: Dental practitioners are exposed to different occupational hazards
      during the course of their professional activity, such as physical, chemical,
      biological, ergonomic factors. The ergonomic hazards, caused by strained posture
      and prolonged repetitive movements, can induce musculoskeletal disorders. It
      occurs in 54-93% of dental professionals and involve the spine, shoulder and hand
      wrist tract. Through a systematic review of international literature, we analyzed
      specific ergonomic risk factors and preventive measures of musculoskeletal
      disorders in professional dental activity. Methods: This systematic review is
      coherent with the PRISMA statement. The scientific research on the major online
      databases was based on the following keywords: dentist, prevention, ergonomic,
      dentistry, musculoskeletal, neck pain, posture, ergonomics, work and
      occupational. The studies included in this review focus on disorders related to
      ergonomics and on the most effective preventive measures to be adopted. No
      restrictions were applied for language or publication type. We excluded reports
      not related to ergonomic prevention in dentistry, reports of minor academic
      significance, editorial articles, individual contributions, and studies published
      in scientific conferences. Results: Online research indicated 4188 references:
      PubMed (2919), Scopus (1257) e Cochrane Library (12). We excluded 3012 of these,
      because they were unrelated to ergonomics theme and 187 due to duplication. From
      the remaining 989 studies, 960 papers did not meet inclusion criteria and they
      were excluded. Therefore, we analyzed 29 articles, including 16 narrative reviews
      and 13 original article. The main risk factor for the development of
      musculoskeletal disorders found in our analysis is static posture adopted during
      work, highlighted in 87.5% of reviews and 84% of original articles. With regard
      to preventive measures, 75% of the reviews highlighted the importance of
      stretching after each working session and at the end of the working day, while
      61.5% of the original articles emphasized the use of modern and ergonomic
      instruments. Discussion: This review showed that static postures are strongly
      responsible in the etiology of musculoskeletal disorders. The awkward postures
      more frequently identified among dental professionals are: extreme forward-head
      and neck flexion; trunk inclination and rotation towards one side; lifting one or
      both shoulders; increased curvature of the thoracic vertebral column; incorrect
      positioning of the lower limbs with thigh-leg angle of less than 90 degrees . It
      is really important to use of a modern workstation with appropriate ergonomic
      supports. Among the preventive ergonomic measures, literature has widely
      recognized the role of physical activity and of a neutral and balanced posture.
      The present review has some limits: a large part of the selected studies did not
      have a high methodological quality score and an inadequate statistical analysis.

PMID- 29362690
TI  - Population genetic structure of Patagonian toothfish (Dissostichus eleginoides)
      in the Southeast Pacific and Southwest Atlantic Ocean.
AB  - Previous studies of population genetic structure in Dissostichus eleginoides have
      shown that oceanographic and geographic discontinuities drive in this species
      population differentiation. Studies have focused on the genetics of D.
      eleginoides in the Southern Ocean; however, there is little knowledge of their
      genetic variation along the South American continental shelf. In this study, we
      used a panel of six microsatellites to test whether D. eleginoides shows
      population genetic structuring in this region. We hypothesized that this species
      would show zero or very limited genetic structuring due to the habitat continuity
      along the South American shelf from Peru in the Pacific Ocean to the Falkland
      Islands in the Atlantic Ocean. We used Bayesian and traditional analyses to
      evaluate population genetic structure, and we estimated the number of putative
      migrants and effective population size. Consistent with our predictions, our
      results showed no significant genetic structuring among populations of the South
      American continental shelf but supported two significant and well-defined genetic
      clusters of D. eleginoides between regions (South American continental shelf and
      South Georgia clusters). Genetic connectivity between these two clusters was
      11.3% of putative migrants from the South American cluster to the South Georgia
      Island and 0.7% in the opposite direction. Effective population size was higher
      in locations from the South American continental shelf as compared with the South
      Georgia Island. Overall, our results support that the continuity of the deep-sea
      habitat along the continental shelf and the biological features of the study
      species are plausible drivers of intraspecific population genetic structuring
      across the distribution of D. eleginoides on the South American continental
      shelf.

PMID- 29362691
TI  - Prediction of life stress on athletes' burnout: the dual role of perceived
      stress.
AB  - Although many studies adopted Smith's (1986) cognitive-affective model of
      athletic burnout in examining stress-burnout relationship, very few studies
      examined the mediating/moderating role of perceived stress on the stress-burnout
      relationship. We sampled 195 college student-athletes and assessed their life
      stress, perceived stress, and burnout. Correlation analyses found all study
      variables correlated. Two separate hierarchical regression analyses found that
      the "distress" component of perceived stress mediated athletes' two types of life
      stress-burnout relationship but "counter-stress" component of perceived stress
      moderated athletes' general-life stress-burnout relationship. We concluded that
      interweaving relationships among athletes' life stress, perceived stress, and
      burnout are not straightforward. Future research should consider the nature of
      athletes life stress, and dual role of perceived stress in examining its'
      association with related psychological responses in athletic settings.

PMID- 29362692
TI  - -Comparative spigot ontogeny across the spider tree of life.
AB  - Spiders are well known for their silk and its varying use across taxa. Very few
      studies have examined the silk spigot ontogeny of the entire spinning field of a
      spider. Historically the spider phylogeny was based on morphological data and
      behavioral data associated with silk. Recent phylogenomics studies have shifted
      major paradigms in our understanding of silk use evolution, reordering
      phylogenetic relationships that were once thought to be monophyletic. Considering
      this, we explored spigot ontogeny in 22 species, including Dolomedes tenebrosus
      and Hogna carolinensis, reported here for the first time. This is the first study
      of its kind and the first to incorporate the Araneae Tree of Life. After rigorous
      testing for phylogenetic signal and model fit, we performed 60 phylogenetic
      generalized least squares analyses on adult female and second instar spigot
      morphology. Six analyses had significant correlation coefficients, suggesting
      that instar, strategy, and spigot variety are good predictors of spigot number in
      spiders, after correcting for bias of shared evolutionary history. We performed
      ancestral character estimation of singular, fiber producing spigots on the
      posterior lateral spinneret whose potential homology has long been debated. We
      found that the ancestral root of our phylogram of 22 species, with the addition
      of five additional cribellate and ecribellate lineages, was more likely to have
      either none or a modified spigot rather than a pseudoflagelliform gland spigot or
      a flagelliform spigot. This spigot ontogeny approach is novel and we can build on
      our efforts from this study by growing the dataset to include deeper taxon
      sampling and working towards the capability to incorporate full ontogeny in the
      analysis.

PMID- 29362693
TI  - Giant ants and their shape: revealing relationships in the genus Titanomyrma with
      geometric morphometrics.
AB  - Shape is a natural phenomenon inherent to many different lifeforms. A modern
      technique to analyse shape is geometric morphometrics (GM), which offers a whole
      range of methods concerning the pure shape of an object. The results from these
      methods have provided new insights into biological problems and have become
      especially useful in the fields of entomology and palaeontology. Despite the
      conspicuous successes in other hymenopteran groups, GM analysis of wings and
      fossil wings of Formicidae has been neglected. Here we tested if landmarks
      defining the wing shape of fossil ants that belong to the genus Titanomyrma are
      reliable and if this technique is able to expose relationships among different
      groups of the largest Hymenoptera that ever lived. This study comprises 402 wings
      from 362 ants that were analysed and assigned with the GM methods linear
      discriminant function analysis, principal component analysis, canonical variate
      analysis, and regression. The giant ant genus Titanomyrma and the parataxon
      Formicium have different representatives that are all very similar but these
      modern methods were able to distinguish giant ant types even to the level of the
      sex. Thirty-five giant ant specimens from the Eckfeld Maar were significantly
      differentiable from a collection of Messel specimens that consisted of 187
      Titanomyrma gigantea females and 42 T. gigantea males, and from 74 Titanomyrma
      simillima females and 21 T. simillima males. Out of the 324 Messel ants, 127 are
      newly assigned to a species and 223 giant ants are newly assigned to sex with GM
      analysis. All specimens from Messel fit to the two species. Moreover, shape
      affinities of these groups and the species Formicium brodiei, Formicium mirabile,
      and Formicium berryi, which are known only from wings, were investigated. T.
      gigantea stands out with a possible female relative in one of the Eckfeld
      specimens whereas the other groups show similar shape patterns that are possibly
      plesiomorphic. Formicidae are one of the most dominant taxa in the animal kingdom
      and new methods can aid in investigating their diversity in the present and in
      deep time. GM of the ant wing delivers significant results and this core of
      methods is able to enhance the toolset we have now to analyse the complex biology
      of the ants. It can prove as especially useful in the future when incorporated
      into better understanding aspects of evolutionary patterns and ant palaeontology.

PMID- 29362694
TI  - Sicegar: R package for sigmoidal and double-sigmoidal curve fitting.
AB  - Sigmoidal and double-sigmoidal dynamics are commonly observed in many areas of
      biology. Here we present sicegar, an R package for the automated fitting and
      classification of sigmoidal and double-sigmoidal data. The package categorizes
      data into one of three categories, "no signal," "sigmoidal," or "double
      sigmoidal," by rigorously fitting a series of mathematical models to the data.
      The data is labeled as "ambiguous" if neither the sigmoidal nor double-sigmoidal
      model fit the data well. In addition to performing the classification, the
      package also reports a wealth of metrics as well as biologically meaningful
      parameters describing the sigmoidal or double-sigmoidal curves. In extensive
      simulations, we find that the package performs well, can recover the original
      dynamics even under fairly high noise levels, and will typically classify curves
      as "ambiguous" rather than misclassifying them. The package is available on CRAN
      and comes with extensive documentation and usage examples.

PMID- 29362695
TI  - Differential response to stress in Ostrea lurida as measured by gene expression.
AB  - Olympia oysters are the only oyster native to the west coast of North America.
      The population within Puget Sound, WA has been decreasing significantly since the
      early 1900's. Current restoration efforts are focused on supplementing local
      populations with hatchery bred oysters. A recent study by Heare et al. (2017) has
      shown differences in stress response in oysters from different locations in Puget
      Sound however, nothing is known about the underlying mechanisms associated with
      these observed differences. In this study, expression of genes associated with
      growth, immune function, and gene regulatory activity in oysters from Oyster Bay,
      Dabob Bay, and Fidalgo Bay were characterized following temperature and
      mechanical stress. We found that heat stress and mechanical stress significantly
      changed expression in molecular regulatory activity and immune response,
      respectively. We also found that oysters from Oyster Bay had the most dramatic
      response to stress at the gene expression level. These data provide important
      baseline information on the physiological response of Ostrea lurida to stress and
      provide clues to underlying performance differences in the three populations
      examined.

PMID- 29362696
TI  - Phylogenetic relationships and genetic diversity of the Polypedates leucomystax
      complex in Thailand.
AB  - Taxonomic uncertainty of the Asian tree frog Polypedates leucomystax complex
      presents the challenging task of inferring its biogeographical history. Here, we
      describe its dispersion and the genetic relationships among different populations
      in Thailand, where we connect the population of the P. leucomystax complex of the
      Sunda Islands to the Indochina (mainland) population based on analyses of 266
      sequences of the mitochondrial cytochrome c oxidase subunit I (COI) gene. Our
      maternal genealogy implies that there are four well-supported lineages in
      Thailand, consisting of Northern A (clade A: Polypedates sp.), Nan (clade B: P.
      cf. impresus), Southern (clade C: P. cf. leucomystax) and Northern D (clade D: P.
      cf. megacephalus), with Bayesian posterior probability >0.9. Phylogeny and
      haplotype networks indicate that clades A, B and D are sympatric. In contrast,
      clade C (P. cf. leucomystax) and clade D (P. cf. megacephalus) are genetically
      divergent due to the geographical barrier of the Isthmus of Kra, resulting in an
      allopatric distribution. Climatic conditions, in particular differences in
      rainfall on each side of the Isthmus of Kra, may play an important role in
      limiting the immigration of both clades. For the within-populations of either
      clades C or D, there was no significant correlation between geographic and
      genetic distance by the isolation-by-distance test, indicating intraspecific
      dispersal of each clade. Population expansion occurred in clade C, whereas clade
      D showed a constant population. Taken together, the P. leucomystax complex in
      South East Asia may have diversified under climatic pressure, leading to
      allopatric and/or sympatric speciation.

PMID- 29362697
TI  - Long-horned Ceratopsidae from the Foremost Formation (Campanian) of southern
      Alberta.
AB  - The horned Ceratopsidae represent one of the last radiations of dinosaurs, and
      despite a decade of intense work greatly adding to our understanding of this
      diversification, their early evolution is still poorly known. Here, two
      postorbital horncores from the upper Foremost Formation (Campanian) of Alberta
      are described, and at ~78.5 Ma represent some of the geologically oldest
      ceratopsid material. The larger of these specimens is incorporated into a fused
      supraorbital complex, and preserves a massive, straight, postorbital horncore
      that is vertical in lateral view, but canted dorsolaterally in rostral view.
      Medially, the supracranial sinus is composed of a small, restricted caudal
      chamber, and a large rostral chamber that forms the cornual diverticulum. This
      morphology is distinct from that of the long-horned Chasmosaurinae, and similar
      to, but still different from, those of younger Centrosaurinae taxa. The smaller
      specimen represents an ontogenetically younger individual, and although showing
      consistent morphology to the larger specimen, is less taxonomically useful.
      Although not certain, these postorbital horns may be referable to a long-horned
      basal (i.e., early-branching, non-pachyrhinosaurini, non-centrosaurini)
      centrosaurine, potentially the contemporaneous Xenoceratops, largely known from
      the parietosquamosal frill. These specimens indicate the morphology of the
      supracranial sinus in early, long-horned members of the Ceratopsidae, and add to
      our understanding of the evolution of the cranial display structures in this
      iconic dinosaur clade.

PMID- 29362698
TI  - Attentional biases toward body images in males at high risk of muscle dysmorphia.
AB  - Objective: Although research on muscle dysmorphia (MD), a body dysmorphic
      disorder subtype, has recently increased, the causes and mechanisms underlying
      this disorder remain unclear. Results from studies examining disorders associated
      with body image suggest the involvement of self-schema in biasing attention
      toward specific body information. The present study examined whether individuals
      at higher risk of MD also display attentional biases toward specific types of
      body images. Methods: The validated Chinese version of the Muscle Appearance
      Satisfaction Scale was used to distinguish men at higher and lower risk of MD.
      Sixty-five adult Chinese men at higher (HRMD, n = 33) and lower risk of MD (LRMD,
      n = 32) performed a visual probe task. Initially, an image of a bodybuilder with
      either larger or smaller musculature was presented on one side of a central
      point, with a neutral image of a car exterior presented on the other side along
      the horizontal plane for 2,000 ms. The paired images were removed, and a visual
      target (a dot) was displayed in the location of one of the previously shown
      images. Participants were asked to indicate the location of the target, and their
      eye movements were recorded during the entire visual presentation. Participant
      reaction time and three eye movement measurements (gaze direction, first saccade
      latency, and first fixation duration) were recorded for use in determining
      attentional bias. Results: The HRMD group revealed biases in orienting and
      maintaining their attention on images of bodybuilders with larger musculatures.
      Participants in this group consequently had a shorter reaction time in
      identifying the target that appeared at the location in which an image of a
      bodybuilder with a larger musculature had been previously displayed. They also
      directed their initial gaze more frequently, had shorter saccade latency, and had
      longer first fixation duration on images of bodybuilders with larger musculatures
      (all p < .0001). In comparison, the LRMD group had longer reaction times, slower
      attention orientation toward body images, and shorter fixation duration for
      images of bodybuilders with larger musculatures (all p < .0001), indicating
      weaker or mixed responses. Discussion: Adult Chinese men at higher risk of MD
      displayed biases in orienting and maintaining their visual attention toward
      images of bodybuilders with larger musculatures, and these biases facilitated
      their information processing. These results suggest that development of MD may be
      due in part to attentional biases associated with established negative self
      schema of specific body information. These findings provide insight into
      understanding and identifying the cognitive characteristics of MD in an Asian
      population.

PMID- 29362699
TI  - Local genic base composition impacts protein production and cellular fitness.
AB  - The maintenance of a G + C content that is higher than the mutational input to a
      genome provides support for the view that selection serves to increase G + C
      contents in bacteria. Recent experimental evidence from Escherichia coli
      demonstrated that selection for increasing G + C content operates at the level of
      translation, but the precise mechanism by which this occurs is unknown. To
      determine the substrate of selection, we asked whether selection on G + C content
      acts across all sites within a gene or is confined to particular genic regions or
      nucleotide positions. We systematically altered the G + C contents of the GFP
      gene and assayed its effects on the fitness of strains harboring each variant.
      Fitness differences were attributable to the base compositional variation in the
      terminal portion of the gene, suggesting a connection to the folding of a
      specific protein feature. Variants containing sequence features that are thought
      to result in rapid translation, such as low G + C content and high levels of
      codon adaptation, displayed highly reduced growth rates. Taken together, our
      results show that purifying selection acting against A and T mutations most
      likely results from their tendency to increase the rate of translation, which can
      perturb the dynamics of protein folding.

PMID- 29362700
TI  - Distributional dynamics of a vulnerable species in response to past and future
      climate change: a window for conservation prospects.
AB  - Background: The ongoing change in climate is predicted to exert unprecedented
      effects on Earth's biodiversity at all levels of organization. Biological
      conservation is important to prevent biodiversity loss, especially for species
      facing a high risk of extinction. Understanding the past responses of species to
      climate change is helpful for revealing response mechanisms, which will
      contribute to the development of effective conservation strategies in the future.
      Methods: In this study, we modelled the distributional dynamics of a 'Vulnerable'
      species, Pseudolarix amabilis, in response to late Quaternary glacial
      interglacial cycles and future 2080 climate change using an ecological niche
      model (MaxEnt). We also performed migration vector analysis to reveal the
      potential migration of the population over time. Results: Historical modelling
      indicates that the range dynamics of P. amabilis is highly sensitive to climate
      change and that its long-distance dispersal ability and potential for
      evolutionary adaption are limited. Compared to the current climatically suitable
      areas for this species, future modelling showed significant migration northward
      towards future potential climatically suitable areas. Discussion: In combination
      with the predicted future distribution, the mechanism revealed by the historical
      response suggests that this species will not be able to fully occupy the future
      expanded areas of suitable climate or adapt to the unsuitable climate across the
      future contraction regions. As a result, we suggest assisted migration as an
      effective supplementary means of conserving this vulnerable species in the face
      of the unprecedentedly rapid climate change of the 21st century. As a study case,
      this work highlights the significance of introducing historical perspectives
      while researching species conservation, especially for currently vulnerable or
      endangered taxa that once had a wider distribution in geological time.

PMID- 29362701
TI  - Analysis of an ATP-induced conformational transition of ABC transporter MsbA
      using a coarse-grained model.
AB  - Upon the binding of ATP molecules to nucleotide binding domains (NBDs), ATP
      binding cassette (ABC) exporters undergo a conformational transition from an
      inward-facing (IF) to an outward-facing (OF) state. This molecular event is a
      typical example of chemo-mechanical coupling. However, the underlying mechanism
      remains unclear. In this study, we analyzed the IF->OF transition of a
      representative ABC exporter, MsbA, by solving the equation of motion under an
      elastic network model (ENM). ATP was represented as a single node in ENM or
      replaced by external forces. When two ATP nodes were added to the ENM of the IF
      state protein, the two NBDs dimerized; subsequently, the two transmembrane
      domains opened toward the extracellular side, resulting in the formation of the
      OF structure. Such a conformational transition was also reproduced by applying
      external forces, which caused the rotational motion of the NBDs instead of the
      addition of ATP nodes. The process of the conformational transition was analyzed
      in detail using cross-correlation maps for node-node interactions. More
      importantly, it was revealed that the ATP binding energy is converted into
      distortion energy of several transmembrane helices. These results are useful for
      understanding the chemo-mechanical coupling in ABC transporters.

PMID- 29362702
TI  - Analysis of the GTPase motif of FlhF in the control of the number and location of
      polar flagella in Vibrio alginolyticus.
AB  - Vibrio alginolyticus normally has a single polar flagellum whose number and
      placement are regulated positively by FlhF. FlhF is a GTPase and homolog of a
      signal recognition particle (SRP) protein called Ffh and SRP receptor FtsY. FlhF
      is located at the cell pole and directs formation of the flagellum. To study the
      mechanism of FlhF localization, we introduced random mutations into flhF by means
      of hydroxylamine and isolated mutants that could not generate the flagellum at
      the cell pole. The novel mutations were only mapped to the GTPase motif of FlhF.
      The mutant FlhF proteins showed reduced polar localization as compared to the
      wild type and still could associate with the membrane. These results support the
      assumption that the GTPase motif of FlhF plays a critical role in the polar
      localization of this protein during formation of the flagellum.

PMID- 29362703
TI  - Chimeric microbial rhodopsins for optical activation of Gs-proteins.
AB  - We previously showed that the chimeric proteins of microbial rhodopsins, such as
      light-driven proton pump bacteriorhodopsin (BR) and Gloeobacter rhodopsin (GR)
      that contain cytoplasmic loops of bovine rhodopsin, are able to activate Gt
      protein upon light absorption. These facts suggest similar protein structural
      changes in both the light-driven proton pump and animal rhodopsin. Here we report
      two trials to engineer chimeric rhodopsins, one for the inserted loop, and
      another for the microbial rhodopsin template. For the former, we successfully
      activated Gs protein by light through the incorporation of the cytoplasmic loop
      of beta2-adrenergic receptor (beta2AR). For the latter, we did not observe any G
      protein activation for the light-driven sodium pump from Indibacter alkaliphilus
      (IndiR2) or a light-driven chloride pump halorhodopsin from Natronomonas
      pharaonis (NpHR), whereas the light-driven proton pump GR showed light-dependent
      G-protein activation. This fact suggests that a helix opening motion is common to
      G protein coupled receptor (GPCR) and GR, but not to IndiR2 and NpHR. Light
      induced difference FTIR spectroscopy revealed similar structural changes between
      WT and the third loop chimera for each light-driven pump. A helical structural
      perturbation, which was largest for GR, was further enhanced in the chimera. We
      conclude that similar structural dynamics that occur on the cytoplasmic side of
      GPCR are needed to design chimeric microbial rhodopsins.

PMID- 29362704
TI  - Structural differences in the bacterial flagellar motor among bacterial species.
AB  - The bacterial flagellum is a supramolecular motility machine consisting of the
      basal body as a rotary motor, the hook as a universal joint, and the filament as
      a helical propeller. Intact structures of the bacterial flagella have been
      observed for different bacterial species by electron cryotomography and
      subtomogram averaging. The core structures of the basal body consisting of the C
      ring, the MS ring, the rod and the protein export apparatus, and their
      organization are well conserved, but novel and divergent structures have also
      been visualized to surround the conserved structure of the basal body. This
      suggests that the flagellar motors have adapted to function in various
      environments where bacteria live and survive. In this review, we will summarize
      our current findings on the divergent structures of the bacterial flagellar
      motor.

PMID- 29362705
TI  - Structural basis for the molecular interactions in DNA damage tolerances.
AB  - DNA damage tolerance (DDT) is a cell function to avoid replication arrest by DNA
      damage during DNA replication. DDT includes two pathways, translesion DNA
      synthesis (TLS) and template-switched DNA synthesis (TS). DDT is regulated by
      ubiquitination of proliferating cell nuclear antigen that binds to double
      stranded DNA and functions as scaffold protein for DNA metabolism. TLS is
      transient DNA synthesis using damaged DNA as a template by error-prone DNA
      polymerases termed TLS polymerases specialized for DNA damage. TS, in which one
      newly synthesized strand is utilized as an undamaged template for replication by
      replicative polymerases, is error-free process. Thus, DDT is not inherently a
      repair pathway. DDT is a mechanism to tolerate DNA damage, giving priority to DNA
      synthesis and enabling finish of DNA replication for cell survival and genome
      stability. DDT is associated with cancer development and thus is of great
      interest in drug discovery for cancer therapy. This review article describes
      recent progress in structural studies on protein-protein and protein-DNA
      complexes involved in TLS and TS, providing the molecular mechanisms of
      interactions in DDT.

PMID- 29362706
TI  - Radial stiffness characteristics of the overlap regions of sarcomeres in isolated
      skeletal myofibrils in pre-force generating state.
AB  - We have studied the stiffness of myofilament lattice in sarcomeres in the pre
      force generating state, which was realized by a relaxing reagent, BDM (butane
      dione monoxime). First, the radial stiffness for the overlap regions of
      sarcomeres of isolated single myofibrils was estimated from the resulting
      decreases in diameter by osmotic pressure applied with the addition of Dextran.
      Then, the radial stiffness was also estimated from force-distance curve
      measurements with AFM technology. The radial stiffness for the overlap regions
      thus obtained was composed of a soft and a rigid component. The soft component
      visco-elastically changed in a characteristic fashion depending on the
      physiological conditions of myofibrils, suggesting that it comes from cross
      bridge structures. BDM treatments significantly affected the soft radial
      component of contracting myofibrils depending on the approach velocity of
      cantilever: It was nearly equal to that in the contracting state at high approach
      velocity, whereas as low as that in the relaxing state at low approach velocity.
      However, comparable BDM treatments greatly suppressed the force production and
      the axial stiffness in contracting glycerinated muscle fibers and also the
      sliding velocity of actin filaments in the in vitro motility assay. Considering
      that BDM shifts the cross-bridge population from force generating to pre-force
      generating states in contracting muscle, the obtained results strongly suggest
      that cross-bridges in the pre-force generating state are visco-elastically
      attached to the thin filaments in such a binding manner that the axial stiffness
      is low but the radial stiffness significantly high similar to that in force
      generating state.

PMID- 29362707
TI  - Decrease in pulmonary function and oxygenation after lung resection.
AB  - Respiratory deficits are common following curative intent lung cancer surgery and
      may reduce the patient's ability to be physically active. We evaluated the
      influence of surgery on pulmonary function, respiratory muscle strength and
      physical performance after lung resection. Pulmonary function, respiratory muscle
      strength (maximal inspiratory/expiratory pressure) and 6-min walk test (6MWT)
      were assessed pre-operatively, 2 weeks post-operatively and 6 months post
      operatively in 80 patients (age 68+/-9 years). Video-assisted thoracoscopic
      surgery was performed in 58% of cases. Two weeks post-operatively, we found a
      significant decline in pulmonary function (forced vital capacity -0.6+/-0.6 L and
      forced expiratory volume in 1 s -0.43+/-0.4 L; both p<0.0001), 6MWT (-37.6+/-74.8
      m; p<0.0001) and oxygenation (-2.9+/-4.7 units; p<0.001), while maximal
      inspiratory and maximal expiratory pressure were unaffected. At 6 months post
      operatively, pulmonary function and oxygenation remained significantly decreased
      (p<0.001), whereas 6MWT was recovered. We conclude that lung resection has a
      significant short- and long-term impact on pulmonary function and oxygenation,
      but not on respiratory muscle strength. Future research should focus on
      mechanisms negatively influencing post-operative pulmonary function other than
      impaired respiratory muscle strength.

PMID- 29362708
TI  - Upper airway involvement in bronchiectasis is marked by early onset and allergic
      features.
AB  - The association of bronchiectasis with chronic rhinosinusitis (CRS) has been
      reported. However, apart from primary ciliary dyskinesia (PCD) and cystic
      fibrosis (CF), predisposing conditions have not been established. We aimed to
      define clinical and laboratory features that differentiate patients with
      bronchiectasis with upper airway symptoms (UASs) and without PCD from patients
      without UASs. We reviewed charts of adults with bronchiectasis, excluding CF and
      PCD. UASs were defined as nasal discharge most days of the year, sinusitis or
      nasal polyps. Laboratory data included IgG, total IgE, blood eosinophils, sputum
      bacteriology and lung function. A radiologist blinded to UAS presence scored
      bronchiectasis (Reiff score) and sino-nasal pathology (Lund-Mackay score). Of 197
      patients, for the 70 (35%) with UASs, symptoms started earlier (34+/-25 versus
      46+/-24 years; p=0.001), disease duration was longer (median 24 versus 12 years;
      p=0.027), exacerbations were more frequent (median 3 versus 2 per year; p=0.14),
      and peripheral blood eosinophil (median 230 versus 200 MUL-1; p=0.015) and total
      IgE (median 100 versus 42 IU.mL-1; p=0.085) levels were higher. The sinus
      computed tomography score was independently associated with exacerbations, with 1
      point on the Lund-Mackay score associated with a 1.03-fold increase in the number
      of exacerbations per year (95% CI 1.0-1.05; p=0.004). These findings may
      implicate a higher disease burden in patients with UASs. We hypothesise that UASs
      precede and may in some cases lead to the development of bronchiectasis.

PMID- 29362709
TI  - Do Tonic Itch and Pain Stimuli Draw Attention towards Their Location?
AB  - Background: Although itch and pain are distinct experiences, both are unpleasant,
      may demand attention, and interfere with daily activities. Research investigating
      the role of attention in tonic itch and pain stimuli, particularly whether
      attention is drawn to the stimulus location, is scarce. Methods: In the
      somatosensory attention task, fifty-three healthy participants were exposed to 35
      second electrical itch or pain stimuli on either the left or right wrist.
      Participants responded as quickly as possible to visual targets appearing at the
      stimulated location (ipsilateral trials) or the arm without stimulation
      (contralateral trials). During control blocks, participants performed the visual
      task without stimulation. Attention allocation at the itch and pain location is
      inferred when responses are faster ipsilaterally than contralaterally. Results:
      Results did not indicate that attention was directed towards or away from the
      itch and pain location. Notwithstanding, participants were slower during itch and
      pain than during control blocks. Conclusions: In contrast with our hypotheses, no
      indications were found for spatial attention allocation towards the somatosensory
      stimuli. This may relate to dynamic shifts in attention over the time course of
      the tonic sensations. Our secondary finding that itch and pain interfere with
      task performance is in-line with attention theories of bodily perception.

PMID- 29362710
TI  - Possible Effect of Concomitant Prokinetics and Herbal Medicines against Nausea in
      Patients Taking Lubiprostone.
AB  - Background and Aim: Lubiprostone is a novel laxative that sometimes causes
      nausea, but preventive strategies remain unconfirmed. Methods: We retrospectively
      chose 126 patients prescribed lubiprostone from 2013 to 2016. Medical records
      were reviewed to clarify whether nausea developed after administration of the
      drug. Background characteristics, including concomitant medicines, were also
      reviewed. Results: The most common adverse symptom was diarrhea (23.8%). Nausea
      occurred in 16 patients (12.7%). Patients taking either prokinetics or herbal
      medicines or both were unlikely to develop nausea (p = 0.007). Conclusions:
      Concomitant prokinetics and/or herbal medicines may help alleviate lubiprostone
      induced nausea.

PMID- 29362711
TI  - Reduction of Skeletal Muscle Power in Adolescent Males Carrying H63D Mutation in
      the HFE Gene.
AB  - Iron overload resulting from the mutation of genes involved in iron metabolism or
      excess dietary intake has been reported to negatively influence human physical
      performance. The aim of this study was to test the hypothesis that adolescents
      bearing a hemochromatosis gene (HFE) mutation in contrast to adults with the same
      mutation will not experience iron accumulation and their aerobic capacity will be
      similar to that of age-matched controls. Thirteen boys participated in the study.
      Seven of them are carriers of H63D mutation in the HFE gene and six were wild
      type. Fitness levels were assessed using the cardiopulmonary exercise test. In
      addition, iron status and inflammatory markers were determined. We observed that
      cardiovascular fitness was significantly lower in the group bearing the HFE
      mutation compared to the control group. Moreover, the HFE mutation group achieved
      lower maximal power output compared to the control group. There were no
      differences in blood ferritin concentrations between the two groups which
      indicates similar amounts of stored iron. Obtained data do not confirm our
      hypothesis. On the contrary, it was demonstrated that HFE mutation is associated
      with a lower level of aerobic capacity, even in the absence of iron accumulation.

PMID- 29362712
TI  - The Difficult Evolution of Intensive Cardiac Care Units: An Overview of the BLITZ
      3 Registry and Other Italian Surveys.
AB  - Coronary care units, initially developed to treat acute myocardial infarction,
      have moved to the care of a broader population of acute cardiac patients and are
      currently defined as Intensive Cardiac Care Units (ICCUs). However, very limited
      data are available on such evolution. Since 2008, in Italy, several surveys have
      been designed to assess ICCUs' activities. The largest and most comprehensive of
      these, the BLITZ-3 Registry, observed that patients admitted are mainly elderly
      males and suffer from several comorbidities. Direct admission to ICCUs through
      the Emergency Medical System was rather rare. Acute coronary syndromes (ACS)
      account for more than half of the discharge diagnoses. However, numbers of acute
      heart failure (AHF) admissions are substantial. Interestingly, age, resources
      availability, and networking have a strong influence on ICCUs' epidemiology and
      activities. In fact, while patients with ACS concentrate in ICCUs with
      interventional capabilities, older patients with AHF or non-ACS, non-AHF cardiac
      diseases prevail in peripheral ICCUs. In conclusion, although ACS is still the
      core business of ICCUs, aging, comorbidities, increasing numbers of non-ACS,
      technological improvements, and resources availability have had substantial
      effects on epidemiology and activities of ICCUs. The Italian surveys confirm
      these changes and call for a substantial update of ICCUs' organization and
      competences.

PMID- 29362713
TI  - Comparison of Optic Nerve Head Blood Flow Autoregulation among Quadrants Induced
      by Decreased Ocular Perfusion Pressure during Vitrectomy.
AB  - Purpose: The present study aimed to examine changes in optic nerve head (ONH)
      blood flow autoregulation in 4 quadrants (superior, nasal, inferior, and
      temporal) with decreased ocular perfusion pressure (OPP) during vitrectomy in
      order to determine whether there is a significant difference of autoregulatory
      capacity in response to OPP decrease at each ONH quadrant. Methods: This study
      included 24 eyes with an epiretinal membrane or macular hole that underwent
      vitrectomy at Toho University Sakura Medical Center. Following vitrectomy, the
      tissue mean blur rate (MBR), which reflects ONH blood flow, was measured. Mean
      tissue MBRs in the four quadrants were generated automatically in the software
      analysis report. Measurements were conducted before and 5 and 10 min after
      intraocular pressure (IOP) elevation of approximately 15 mmHg in the subjects
      without systemic disorders. Results: The baseline tissue MBR of the temporal
      quadrant was significantly lower than that of the other 3 quadrants (all P <
      0.05). However, the time courses of tissue MBR in response to OPP decrease were
      not significantly different among the four quadrants during vitrectomy (P =
      0.23). Conclusions: There is no significant difference in the autoregulatory
      capacity of the four ONH quadrants in patients without systemic disorders during
      vitrectomy.

PMID- 29362714
TI  - Inferring Molecular Processes Heterogeneity from Transcriptional Data.
AB  - RNA microarrays and RNA-seq are nowadays standard technologies to study the
      transcriptional activity of cells. Most studies focus on tracking transcriptional
      changes caused by specific experimental conditions. Information referring to
      genes up- and downregulation is evaluated analyzing the behaviour of relatively
      large population of cells by averaging its properties. However, even assuming
      perfect sample homogeneity, different subpopulations of cells can exhibit diverse
      transcriptomic profiles, as they may follow different regulatory/signaling
      pathways. The purpose of this study is to provide a novel methodological scheme
      to account for possible internal, functional heterogeneity in homogeneous cell
      lines, including cancer ones. We propose a novel computational method to infer
      the proportion between subpopulations of cells that manifest various functional
      behaviour in a given sample. Our method was validated using two datasets from RNA
      microarray experiments. Both experiments aimed to examine cell viability in
      specific experimental conditions. The presented methodology can be easily
      extended to RNA-seq data as well as other molecular processes. Moreover, it
      complements standard tools to indicate most important networks from
      transcriptomic data and in particular could be useful in the analysis of cancer
      cell lines affected by biologically active compounds or drugs.

PMID- 29362715
TI  - Prevalence of Thyroid Abnormalities in Thai Patients with Vitiligo.
AB  - Background: Vitiligo is an acquired hypopigmentary disorder. The prevalence of
      vitiligo is 0.1-2% worldwide. Numerous autoimmune diseases are associated with
      vitiligo, including autoimmune thyroid diseases. The prevalence of thyroid
      abnormalities is up to 34% in vitiligo patients depending on ethnicities.
      Objective: This study aims to investigate thyroid abnormalities in Thai patients
      with vitiligo. Methods: Medical records of vitiligo patients attending outpatient
      dermatology clinic at a university-based hospital from 2012 to 2016 were
      retrospectively reviewed. Data regarding vitiligo, clinical features, and
      autoimmune thyroid laboratory results were retrieved and analyzed. Results: Among
      325 vitiligo patients identified, anti-thyroid peroxidase and anti-thyroglobulin
      were positive in 90 (27.7%) and 63 patients (19.4%), respectively. Positive
      thyroid antibody was associated with female gender (p < 0.001) and vitiliginous
      hand lesions (p < 0.02). Out of 197 patients with complete thyroid function test,
      the prevalence of autoimmune thyroid diseases (AITD) is 12.7%. Female,
      nonsegmental type, higher affected area, and the presence of leukotrichia are
      significantly associated with AITD in vitiligo patients. Conclusions: Prevalence
      of positive thyroid antibodies and AITD in Thai patients with vitiligo is
      compatible with previous studies around the world. Screening for AITD with
      thyroid antibodies and serum TSH is essential for vitiligo patients.

PMID- 29362716
TI  - Efficacy of Fluoride Varnishes with Added Calcium Phosphate in the Protection of
      the Structural and Mechanical Properties of Enamel.
AB  - The aim of this study was to investigate the efficacy of various fluoride
      varnishes in the protection of the structural and nanomechanical properties of
      dental enamel. Demineralized enamel specimens were imaged using a high-resolution
      micro-CT system and lesion parameters including mineral density and lesion depth
      were extracted from mineral density profiles. Nanoindentation elastic modulus and
      hardness were calculated as a function of penetration depth from the load
      displacement curves. The average depth of the lesion in specimens with no prior
      fluoride varnish treatment was 86 +/- 7.19 MUm whereas the varnish treated
      specimens had an average depth of 67 +/- 7.03 MUm (P < 0.05). The mineral density
      of enamel lesions with no fluoride varnish treatment had an average of 1.85
      gr/cm3 which was 25% lower than the corresponding value in varnish treated enamel
      and 37% lower than sound enamel. While, in the varnish treated group, elastic
      modulus and hardness values had decreased by 18% and 23%, respectively, the
      corresponding values in the non-varnish treated specimens had a reduction of 43%
      and 54% compared to the sound enamel. The findings from this study highlight the
      preventive role of fluoride varnishes. Addition of calcium and phosphate does not
      seem to enhance or inhibit the prevention or remineralization performance of
      fluoride varnishes.

PMID- 29362717
TI  - Association between Fluorescent Advanced Glycation End-Products and Vascular
      Complications in Type 2 Diabetic Patients.
AB  - Objectives: Diabetes is a major health problem associated with hyperglycemia and
      chronically increased oxidative stress and enhanced formation of advanced
      glycation end-products (AGEs). The aim of this study was to determine whether
      oxidative plasma biomarkers in diabetic patients could be evidenced and
      associated with vascular complications. Methods: Oxidative stress biomarkers such
      as thiols, ischemia-modified albumin (IMA), glycated albumin (GA), fructosamine,
      and AGEs were measured in 75 patients with poorly controlled type 2 diabetes
      (HbA1c > 7.5%) with (44) or without (31) vascular disease and in 31 nondiabetic
      controls. Results: Most biomarkers of oxidation and glycation were significantly
      increased in diabetic patients in comparison with nondiabetics. Fructosamines,
      GA, IMA, and AGEs were positively correlated and levels of fluorescent AGEs were
      significantly increased in the plasma from patients presenting vascular
      complication. Conclusions: These results bring new evidence for the potential
      interest of glycated albumin, oxidative stress, and glycoxidation parameters in
      the monitoring of type 2 diabetic patients. Furthermore, it emphasizes
      fluorescent AGEs as a putative indicator for vascular event prediction in
      diabetic patients.

PMID- 29362718
TI  - Paeoniflorin, the Main Active Ingredient of Shuyu Capsule, Inhibits Cav1.2 and
      Regulates Calmodulin/Calmodulin-Dependent Protein Kinase II Signalling.
AB  - The aim of this study was to explore the mechanism underlying the antidepression
      activity of paeoniflorin, the main active ingredient of paeony extract and Shuyu
      capsules, and determine its effect on the calmodulin/calmodulin-dependent protein
      kinase II (CaM/CaMKII) signalling pathway and on the possible target, the voltage
      gated calcium channel (Cav). Rats at the nonacceptance stage were selected for
      premenstrual syndrome (PMS) depression modelling. Behavioural assays were used
      for model testing. Rats were given Shuyu capsules, paeony extract, and bupleurum.
      Western blot analysis was used to assess the expression levels of calcium voltage
      gated channel subunit alpha 1 C (CACNA1C), brain-derived neurotrophic factor, and
      CaM/CaMKII signalling pathway proteins. Intracellular Ca2+ concentration in CHO
      cell line was measured using Fluo-4-AM and whole-cell patch clamps. The PMS
      depression model was successfully established and demonstrated that Shuyu can
      mitigate depressive behaviour in a rat PMS model. Paeony extract did not affect
      CACNA1C protein expression in rat hippocampi but did affect Cav1.2-mediated
      CaM/CaMKII signalling pathways. Paeoniflorin significantly inhibited KCl-induced
      increases in intracellular Ca2+ concentration and Cav1.2 current density.
      Further, it may function via the CaM/CaMKII pathway and its downstream signalling
      molecules by regulating Cav1.2, thus playing an important role in the treatment
      and alleviation of affective disorders.

PMID- 29362719
TI  - A Clinical Mentorship and Quality Improvement Program to Support Health Center
      Nurses Manage Type 2 Diabetes in Rural Rwanda.
AB  - Introduction: The prevalence of diabetes mellitus is rapidly rising in SSA.
      Interventions are needed to support the decentralization of services to improve
      and expand access to care. We describe a clinical mentorship and quality
      improvement program that connected nurse mentors with nurse mentees to support
      the decentralization of type 2 diabetes care in rural Rwanda. Methods: This is a
      descriptive study. Routinely collected data from patients with type 2 diabetes
      cared for at rural health center NCD clinics between January 1, 2013 and December
      31, 2015, were extracted from EMR system. Data collected as part of the clinical
      mentorship program were extracted from an electronic database. Summary statistics
      are reported. Results: The patient population reflects the rural settings, with
      low rates of traditional NCD risk factors: 5.6% of patients were current smokers,
      11.0% were current consumers of alcohol, and 11.9% were obese. Of 263 observed
      nurse mentee-patient encounters, mentor and mentee agreed on diagnosis 94.4% of
      the time. Similarly, agreement levels were high for medication, laboratory exam,
      and follow-up plans, at 86.3%, 87.1%, and 92.4%, respectively. Conclusion: Nurses
      that receive mentorship can adhere to a type 2 diabetes treatment protocol in
      rural Rwanda primary health care settings.

PMID- 29362720
TI  - Maternal Dietary Patterns and Gestational Diabetes Risk: A Case-Control Study.
AB  - Background: Maternal dietary patterns play an important role in the progress of
      gestational diabetes mellitus (GDM). The aim of the present study was to explore
      this association. Method: A total of 388 pregnant women (122 case and 266
      control) were included. Dietary intake were collected using a food frequency
      questionnaire (FFQ). GDM was diagnosed using a 100-gram, 3-hour oral glucose
      tolerance test. Dietary pattern was identified by factor analysis. To investigate
      the relation between each of the independent variables with gestational diabetes,
      the odds ratio (OR) was calculated. Results: Western dietary pattern was high in
      sweets, jams, mayonnaise, soft drinks, salty snacks, solid fat, high-fat dairy
      products, potatoes, organ meat, eggs, red meat, processed foods, tea, and coffee.
      The prudent dietary pattern was characterized by higher intake of liquid oils,
      legumes, nuts and seeds, fruits and dried fruits, fish and poultry whole, and
      refined grains. Western dietary pattern was associated with increased risk of
      gestational diabetes mellitus before and after adjustment for confounders (OR =
      1.97, 95% CI: 1.27-3.04, OR = 1.68, 95% CI: 1.04-2.27). However, no significant
      association was found for a prudent pattern. Conclusion: These findings suggest
      that the Western dietary pattern was associated with an increased risk of GDM.

PMID- 29362721
TI  - Diabetes Prevention, Early Intervention, and Nondrug Therapy.

PMID- 29362723
TI  - Durability of Telbivudine-Associated Improvement of Renal Function Following
      Withdrawal or Switching of Antivirals in Chronic Hepatitis B Patients.
AB  - Background: Besides antiviral activities against hepatitis B virus (HBV),
      telbivudine has an extrahepatic pharmaceutical effect: to improve renal function
      assessed by estimated glomerular filtration rate (eGFR). However, the durability
      of this effect after withdrawal of telbivudine or switching to other antivirals
      has never been investigated. Methods: We conducted a postmarketing, real-world
      observation study for telbivudine treatment. The durability of telbivudine
      associated renal function improvement was examined following withdrawal/switching
      of antivirals. Results: Of 160 telbivudine-treated, chronic hepatitis B patients,
      21, 6, and 2 patients were loss to follow-up, dead, and pregnant during the
      study, respectively. Of the remaining 131 patients, 26, 47, 28, and 30 patients
      experienced telbivudine withdrawal, continuous use of telbivudine, switching to
      entecavir, or switching to tenofovir, respectively. During the first 2 years,
      eGFR in telbivudine-treated patients significantly improved before
      withdrawal/switching of antivirals (P = .009). Thereafter, eGFR remained
      unchanged for >1 year in the withdrawal (P = .100) and continuous use (P = .517)
      subgroups, but decreased significantly in the switching to entecavir (P = .002)
      and switching to tenofovir (P < .001) subgroups. Multivariate logistic regression
      analysis revealed that switching to tenofovir and poor liver functional reserve
      were predictors for eGFR deterioration. Conclusions: Telbivudine-associated renal
      function improvement was durable after withdrawal or continuous use of
      telbivudine. However, renal function deteriorated if patients were switched to
      entecavir or tenofovir.

PMID- 29362722
TI  - The Identification of Key Genes and Pathways in Glioma by Bioinformatics
      Analysis.
AB  - Glioma is the most common malignant tumor in the central nervous system. This
      study aims to explore the potential mechanism and identify gene signatures of
      glioma. The glioma gene expression profile GSE4290 was analyzed for
      differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia
      of Genes and Genomes (KEGG) analyses were applied for the enriched pathways. A
      protein-protein interaction (PPI) network was constructed to find the hub genes.
      Survival analysis was conducted to screen and validate critical genes. In this
      study, 775 downregulated DEGs were identified. GO analysis demonstrated that the
      DEGs were enriched in cellular protein modification, regulation of cell
      communication, and regulation of signaling. KEGG analysis indicated that the DEGs
      were enriched in the MAPK signaling pathway, endocytosis, oxytocin signaling, and
      calcium signaling. PPI network and module analysis found 12 hub genes, which were
      enriched in synaptic vesicle cycling rheumatoid arthritis and collecting duct
      acid secretion. The four key genes CDK17, GNA13, PHF21A, and MTHFD2 were
      identified in both generation (GSE4412) and validation (GSE4271) dataset,
      respectively. Regression analysis showed that CDK13, PHF21A, and MTHFD2 were
      independent predictors. The results suggested that CDK17, GNA13, PHF21A, and
      MTHFD2 might play important roles and potentially be valuable in the prognosis
      and treatment of glioma.

PMID- 29362724
TI  - Association of Suboptimal Antiretroviral Therapy Adherence With Inflammation in
      Virologically Suppressed Individuals Enrolled in the SMART Study.
AB  - Suboptimal (ie, <100%) antiretroviral therapy (ART) adherence has been associated
      with heightened inflammation in cohort studies, even among people with virologic
      suppression. We aimed to evaluate this association among participants in the
      Strategies for Management of Antiretroviral Therapy (SMART) study who had
      virologic suppression (HIV-1 VL < 200 copies/mL) at enrollment. Based on self
      reported adherence (7-day recall), plasma concentrations of interleukin 6 and D
      dimer were 9% (95% confidence interval [CI], 1%-18%; P = .02) and 11% (95% CI, 1%
      22%; P = .03) higher in participants who reported suboptimal vs 100% adherence,
      respectively. These findings confirm previous observations and support the
      hypothesis that suboptimal ART adherence, even in the context of virologic
      suppression, may have significant biological consequences. ClinicalTrials.gov
      number NCT00027352.

PMID- 29362725
TI  - Male Involvement in Maternal Health Care at Anomabo, Central Region, Ghana.
AB  - Background: Globally, male involvement in maternal health care services remains a
      challenge to effective maternal health care accessibility and utilization.
      Objective: This study assessed male involvement in maternal health care services
      and associated factors in Anomabo in the Central Region of Ghana. Methods: Random
      sampling procedures were employed in selecting 100 adult male respondents whose
      partners were pregnant or had given birth within twelve months preceding the
      study. Pearson Chi-Square and Fisher's exact tests were conducted to assess the
      association of sociodemographic and enabling/disenabling factors with male
      involvement in maternal health care services. Results: Some 35%, 44%, and 20% of
      men accompanied their partners to antenatal care, delivery, and postnatal care
      services, respectively. Male involvement in antenatal care and delivery was
      influenced by sociodemographic (partner's education, type of marriage, living
      arrangements, and number of children) and enabling/disenabling (distance to
      health facility, attitude of health workers, prohibitive cultural norms,
      unfavourable health policies, and gender roles) factors. Conclusion: The low male
      involvement in maternal health care services warrants interventions to improve
      the situation. Public health interventions should focus on designing messages to
      diffuse existing sociocultural perceptions and health care provider attitudes
      which influence male involvement in maternal health care services.

PMID- 29362727
TI  - Two Cases of Atezolizumab-Induced Hypophysitis.
AB  - Cancer immunotherapy has emerged as treatment of multiple advanced cancer types.
      Immune checkpoint inhibitors, namely anticytotoxic T-lymphocyte antigen-4 (CTLA
      4), antiprogrammed cell death-1 (PD-1), and antiprogrammed cell death-1 ligand 1
      (PD-L1) antibodies, have been used for treatment of various cancers. Classified
      as immune-related adverse events, several endocrinopathies, including
      hypophysitis, are associated with these agents. Although anti-CTLA-4-induced
      hypophysitis has been frequently observed, hypophysitis upon use of anti-PD-1 and
      anti-PD-L1 antibodies is rare. Case 1 is a 65-year-old man presented with a stage
      IV non-small cell lung cancer (NSCLC) treated with atezolizumab (an anti-PD-L1
      antibody) following several inefficacious chemotherapies. After 56 weeks of the
      treatment, he complained of general malaise and appetite loss, and was diagnosed
      with adrenal insufficiency. Endocrinological examination revealed isolated
      adrenocorticotropic hormone (ACTH) deficiency; pituitary magnetic resonance
      imaging (MRI) showed anterior pituitary atrophy. Hydrocortisone replacement
      therapy rapidly improved his symptoms and enabled him to continue atezolizumab
      therapy. Case 2 is a 70-year-old man with a stage IV NSCLC treated with
      atezolizumab. After 52 weeks of treatment, he was diagnosed with isolated ACTH
      deficiency. Pituitary MRI revealed no obvious abnormalities in the anterior
      pituitary. Hydrocortisone replacement therapy was also efficacious. We report two
      cases of atezolizumab-induced hypophysitis. Both showed isolated ACTH deficiency,
      suggesting similar clinical characteristics of hypophysitis associated with the
      use of anti-PD-1 antibodies. These results suggest a caution for the late-onset
      central adrenal insufficiency associated with hypophysitis in patients treated
      with anti-PD-L1 antibodies.

PMID- 29362728
TI  - ewrapper: Operationalizing engagement strategies in mHealth.
AB  - The advancement of digital technologies particularly in the domain of mobile
      health (mHealth) holds great promise in the promotion of health behavior.
      However, keeping users engaged remains a central challenge. This paper proposes a
      novel approach to address this issue by supplementing existing and future mHealth
      applications with an engagement wrapper - a collection of engagement strategies
      integrated into a single, coherent model. The engagement wrapper is
      operationalized within the format of an ambient display on the lock screen of
      mobile devices.

PMID- 29362729
TI  - DNA microarray-based resonance light scattering assay for multiplexed detection
      of DNA mutation in papillary thyroid cancer.
AB  - Highly accurate analysis of single-nucleotide polymorphisms (SNPs) plays an
      important role in both disease diagnostics and personalized medicine development.
      In this work, a DNA microarray-based resonance light scattering (RLS) assay has
      been developed for multiplexed detection of papillary thyroid carcinoma (PTC)
      related mutation points including BRAFV600E (t1m), NRAS codon 61 (t2m), TERT
      promoter g.1295228 (t31m) and TERT promoter g.1295250 (t32m) with high
      sensitivity and selectivity by the attachment of polyvalent ssDNA modified 13 nm
      gold nanoparticles (ssDNAs@GNPs) followed by silver deposition for signal
      enhancement. The microarray-based RLS assay provides a detection limit (S/N = 3)
      at the sub-nanomolar level for the target ssDNAs and determines allele
      frequencies as low as 0.2% for t1m, 0.2% for t2m, 0.5% for t31m, and 0.5% for
      t32m in the cocktail of target ssDNAs, respectively. The practicability of the
      DNA microarray-based RLS assay is demonstrated by profiling of t2m in 50 clinical
      thyroid tissue samples of PTC patients, and satisfactory results are obtained.

PMID- 29362726
TI  - Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of
      Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD).
AB  - Chronic exposure to 4-vinylcycloxene diepoxide (VCD) in rodents accelerates the
      natural process of ovarian follicular atresia modelling perimenopause in women.
      We investigated why estrogen therapy is beneficial for symptomatic women despite
      normal or high estrogen levels during perimenopause. Female rats (28 d) were
      injected daily with VCD or oil for 15 d; 55-65 d after the first injection,
      pellets of 17beta-estradiol or oil were inserted subcutaneously. Around 20 d
      after, the rats were euthanized (control rats on diestrus and estradiol-treated
      21 d after pellets implants). Blood was collected for hormone measurement, the
      brains were removed and dorsal raphe nucleus (DRN), hippocampus (HPC), and
      amygdala (AMY) punched out for serotonin (5-HT), estrogen receptor beta (ERbeta),
      and progesterone receptor (PR) mRNA level measurements. Another set of rats was
      perfused for tryptophan hydroxylase (TPH) immunohistochemistry in the DRN.
      Periestropausal rats exhibited estradiol levels similar to controls and a lower
      progesterone level, which was restored by estradiol. The DRN of periestropausal
      rats exhibited lower expression of PR and ERbeta mRNA and a lower number of TPH
      cells. Estradiol restored the ERbeta mRNA levels and number of serotonergic cells
      in the DRN caudal subregion. The 5-HT levels were lower in the AMY and HPC in
      peristropausal rats, and estradiol treatment increased the 5-HT levels in the HPC
      and also increased ERbeta expression in this area. In conclusion, estradiol may
      improve perimenopause symptoms by increasing progesterone and boosting serotonin
      pathway from the caudal DRN to the dorsal HPC potentially through an increment in
      ERbeta expression in the DRN.

PMID- 29362730
TI  - Temperature dependent excited state dynamics in dual emissive CdSe nano
      tetrapods.
AB  - Time resolved spectroscopic investigation has been performed on nano-tetrapods,
      which are exotic nanocrystals with zinc blende type core structure and four arms
      with wurtzite structure. Dual emission is observed in these nanostructures. A
      band-edge emission occurs at 500-600 nm and a broad surface state emission occurs
      in the 600-900 nm region. The band-edge emission decays almost completely in a
      few ps, indicating the operation of an efficient trapping process. Incomplete
      recovery kinetics of ground state bleach from transient absorption experiments
      signifies the existence of a long-lived excited state. The lifetime of the
      surface state emission is in tens of nanoseconds. At liquid nitrogen temperature,
      surface state emission is enhanced to a greater degree than band edge emission,
      indicating suppression of various deactivation pathways at this temperature.
      Thus, an idea of excited state dynamics of these systems is developed, with a
      view of future tuning of photoluminescence properties by playing with the
      different radiative and nonradiative pathways involved.

PMID- 29362731
TI  - Enzyme-free quantification of exosomal microRNA by the target-triggered assembly
      of the polymer DNAzyme nanostructure.
AB  - We herein report an efficient hybridization chain reaction (HCR)- and DNAzyme
      based enzyme-free signal amplification for the detection of specific exosomal
      miRNAs in the culture medium of cancer cells and serum samples from cancer
      patients via the target-triggered self-assembly of the polymer DNAzyme
      nanostructure.

PMID- 29362732
TI  - Deducing disulfide patterns of cysteine-rich proteins using signature fragments
      produced by top-down mass spectrometry.
AB  - Direct mapping of protein disulfide patterns using top-down mass spectrometry
      (MS) is often hampered by inadequate fragmentation at the disulfide-enclosing
      region, and insufficient structural information provided by the fragments. Here
      we used electron-transfer/high energy collision dissociation (EThcD) to improve
      the fragmentation efficiency, and developed strategies that minimize the false
      positive identification of fragments and deconvolute the signals representing
      specific modifications made to the disulfide-cleavage-induced fragments. We
      observed clear correlations between unique modification (attachment or removal of
      H or SH) patterns and the number of disulfide bonds that enclose the
      corresponding region. Using the characteristic signature fragments, we in part
      localized the Cys-bridging sites in disulfide-scrambled lysozymes, and reduced
      the number of putative disulfide patterns from 104 to 6. The results demonstrated
      the feasibility of direct analysis of complex disulfide patterns using top-down
      MS.

PMID- 29362733
TI  - Probing beta amyloid aggregation using fluorescence anisotropy: experiments and
      simulation.
AB  - The aggregation of beta amyloid (Ab) protein is associated with the development
      of Alzheimer's disease. In this work we monitor Ab aggregation using fluorescence
      anisotropy, a technique that provides information on the rotational diffusion of
      the fluorescing tyrosine (Tyr) side chains. We also perform Monte Carlo (MC) and
      fully atomistic Molecular Dynamics (MD) simulations to interpret the experiments.
      The experimental results show that there are two different rotational timescales
      contributing to the anisotropy. Our MC simulation captures this behaviour in a
      coarse-scale manner, and, more importantly, shows that the Tyr side chains must
      have their movements restricted in order to reproduce the anisotropy. The MD
      simulations provide a molecular scale view, and indeed show that aggregation
      restricts the Try side chains to yield anisotropy in line with the experimental
      results. This combination of experiment and simulation therefore provides a
      unique insight into the aggregation process, and we suggest how this approach
      might be used to gain further information on aggregating protein systems.

PMID- 29362734
TI  - Investigation of compacted DNA structures induced by Na+ and K+ monovalent
      cations using biological nanopores.
AB  - In aqueous solutions, an elongated, negatively charged DNA chain can quickly
      change its conformation into a compacted globule in the presence of positively
      charged molecules, or cations. This well-known process, called DNA compaction, is
      a method with great potential for gene therapy and delivery. Experimental
      conditions to induce these compacted DNA structures are often limited to the use
      of common compacting agents, such as cationic surfactants, polymers, and
      multivalent cations. In this study, we show that in highly concentrated buffers
      of 1 M monovalent cation solutions at pH 7.2 and 10, biological nanopores allow
      real-time sensing of individual compacted structures induced by K+ and Na+, the
      most abundant monovalent cations in human bodies. Herein, we studied the ratio
      between compacted and linear structures for 15-mer single-stranded DNA molecules
      containing only cytosine nucleotides, optimizing the probability of linear DNA
      chains being compacted. Since the binding affinity of each nucleotide to cation
      is different, the ability of the DNA strand to fold into a compacted structure
      greatly depends on the type of cations and nucleotides present. Our experimental
      results compare favorably with findings from previous molecular dynamics
      simulations for the DNA compacting potential of K+ and Na+ monovalent cations. We
      estimate that the majority of single-stranded DNA molecules in our experiment are
      compacted. From the current traces of nanopores, the ratio of compacted DNA to
      linear DNA molecules is approximately 30 : 1 and 15 : 1, at a pH of 7.2 and 10,
      respectively. Our comparative studies reveal that Na+ monovalent cations have a
      greater potential of compacting the 15C-ssDNA than K+ cations.

PMID- 29362735
TI  - Effects of different substituents of methyl 5-R-salicylates on the excited state
      intramolecular proton transfer process.
AB  - The proton transfer reaction in methyl 5-R-salicylate is found to be highly
      sensitive to the presence of specific substituents in resonance with the hydroxyl
      group, leading to different fluorescence behaviors of methyl 5-R-salicylate with
      different substituents (J. Catalan, J. Phys. Chem. B, 2015, 119, 2132). But a
      detailed survey of its reaction mechanism is lacking. In our research, the
      hydrogen bond strengthening behavior in excited states is affected by the
      different substituents that have been reported for the first time. Absorption and
      emission spectra calculated for the work presented here agree well with
      experimental results. At the same time, in order to provide a reliable
      description of the reaction energy profiles, we compare the barrier differences
      obtained using CAM-B3LYP and B3LYP methods, and we visually observe the effect of
      different substituents on the ESIPT reactions in methyl 5-R-salicylates by
      combining the potential energy curves. So the excited state intramolecular proton
      transfer (ESIPT) reactions in methyl 5-R-salicylate molecules are investigated in
      detail using density functional theory (DFT) and time dependent density
      functional theory (TDDFT) methods. It can be confirmed that the mobility of the
      intramolecular pi electrons is affected by an increase in the resonant strength
      of the different substituents and hydroxyl groups. As a consequence, a hydrogen
      bonding interaction gradual weakening mechanism has been perfectly verified, that
      is, the ESIPT reaction is more difficult to occur from MS -> 5MeMS -> 5FMS ->
      5ClMS -> 5BrMS -> 5MeOMS -> 5AmMS molecules.

PMID- 29362736
TI  - Enzymatic asymmetric synthesis of chiral amino acids.
AB  - Chiral amino acids are extensively applied in the pharmaceutical, food, cosmetic,
      agricultural, and feedstuff industries. The development of synthetic
      methodologies for optically pure amino acids has been driven by their significant
      applications. Among the various synthesis methods for the production of chiral
      amino acids, enzymatic asymmetric synthesis is a unique preparation strategy that
      shows great potential. This review provides an overview of the reported methods
      for enzymatic asymmetric synthesis of chiral amino acids, including asymmetric
      reductive amination of keto acids, asymmetric transfer of an amino group to keto
      acids, enantioselective addition of ammonia to alpha,beta-unsaturated acids, and
      aldol condensation of an amino acid to aldehydes.

PMID- 29362747
TI  - Plasmonic behaviour and plasmon-induced charge separation of nanostructured MoO3
      x under near infrared irradiation.
AB  - Plasmon-induced charge separation (PICS) allows direct conversion of localized
      surface plasmon resonance (LSPR) to electron flows and photoelectrochemical
      reactions. However, PICS has only been achieved using plasmonic noble metal
      nanoparticles, not with compound nanoparticles. In order to achieve compound
      PICS, MoO3-x nanostructures were prepared that exhibit LSPR in the near infrared
      region by using metal oxides or metal nanoparticles as templates. Solid-state
      cells based on the MoO3-x nanostructure were developed. Their photoresponse to
      700-1400 nm infrared light was investigated and analyzed on the basis of their
      PICS mechanisms.

PMID- 29362748
TI  - Fluorescent excimers and exciplexes of the purine base derivative 8-phenylethynyl
      guanine in DNA hairpins.
AB  - The ground- and excited-state electronic interactions between the nucleobase
      analog 8-(4'-phenylethynyl)deoxyguanosine, EG, with natural nucleobases and 7
      deazaguanine, as well as between adjacent EG base analogs, have been
      characterized using a combination of steady-state spectroscopy and time-resolved
      fluorescence, absorption, and stimulated Raman spectroscopies. The properties of
      the nucleoside EG-H2 are only weakly perturbed upon incorporation into synthetic
      DNA hairpins in which thymine, cytosine or adenine are the bases flanking EG.
      Incorporation of the nucleoside to be adjacent to guanine or deazaguanine results
      in the formation of short-lived (40-80 ps) exciplexes, the charge transfer
      character of which increases as the oxidation potential of the donor decreases.
      Hairpins possessing two or three adjacent EG base analogs display exciton-coupled
      circular dichroism in the ground state and form long-lived fluorescent excited
      states upon electronic excitation. Incorporation of EG into the helical scaffold
      of the DNA hairpins places it adjacent to its neighboring nucleobases or a second
      EG, thus providing the close proximity required for the formation of exciplex or
      excimer intermediates upon geometric relaxation of the short-lived EG excited
      state. The three time-resolved spectroscopic methods employed permit both the
      characterization of the several intermediates and the kinetics of their formation
      and decay.

PMID- 29362749
TI  - Adsorption equilibrium of nitrogen dioxide in porous materials.
AB  - The effect of confinement on the equilibrium reactive system containing nitrogen
      dioxide and dinitrogen tetroxide is studied by molecular simulation and the
      reactive Monte Carlo (RxMC) approach. The bulk-phase reaction was successfully
      reproduced and five all-silica zeolites (i.e. FAU, FER, MFI, MOR, and TON) with
      different topologies were selected to study their adoption behavior. Dinitrogen
      tetroxide showed a stronger affinity than nitrogen dioxide in all the zeolites
      due to size effects, but exclusive adsorption sites in MOR allowed the adsorption
      of nitrogen dioxide with no competition at these sites. From the study of the
      adsorption isotherms and isobars of the reacting mixture, confinement enhanced
      the formation of dimers over the full range of pressure and temperature, finding
      the largest deviations from bulk fractions at low temperature and high pressure.
      The channel size and shape of the zeolite have a noticeable influence on the
      dinitrogen tetroxide formation, being more important in MFI, closely followed by
      TON and MOR, and finally FER and FAU. Preferential adsorption sites in MOR lead
      to an unusually strong selective adsorption towards nitrogen dioxide,
      demonstrating that the topological structure has a crucial influence on the
      composition of the mixture and must be carefully considered in systems containing
      nitrogen dioxide.

PMID- 29362750
TI  - Charge recombination control for high efficiency CdS/CdSe quantum dot co
      sensitized solar cells with multi-ZnS layers.
AB  - ZnS as an inorganic passivation agent has been proven to be effective in
      suppressing charge recombination and enhancing power conversion efficiency (PCE)
      in quantum dot-sensitized solar cells (QDSCs). In the present study, we
      constructed a novel TiO2/ZnS/CdS/ZnCdS/CdSe/ZnS photoelectrode via successive
      ionic layer adsorption and reaction (SILAR) and chemical bath deposition (CBD).
      The complementary effects of multi-ZnS layers on the optical and electrochemical
      performance of the QDSCs were systematically investigated. The multi-ZnS can not
      only facilitate the growth and distribution of QDs, but also suppress the
      different interface charge recombination effectively. We suggest that the
      formation of the ZnCdS intermediate layers via ion-exchange route during CBD
      process contributes to the higher photoelectrochemical cell performance of the
      QDSCs with the middle ZnS layer. When the three-layer ZnS was employed in
      CdS/CdSe co-sensitized system, the PCE reached 6.05%, which is much higher than
      that observed for solar cells with the conventional single ZnS treatments and the
      two layers inserted at the interface between CdS QDs and CdSe QDs and electrolyte
      (4.80% and 5.42%, respectively).

PMID- 29362751
TI  - Computational evidence for a reaction pathway bifurcation in Sasaki-type (4 + 3)
      cycloadditions.
AB  - The current report seeks to validate the existence of a post-transition state
      bifurcation in the Lewis acid-catalysed (4 + 3)-cycloaddition of butadiene and
      alpha-methoxy acrolein. Cycloaddition transition state (TS) structures are shown
      by intrinsic reaction coordinate (IRC) and potential energy surface (PES) scan
      calculations to connect directly to both (4 + 3)- and (4 + 2)-products. A second
      TS, a 1,2-sigmatropic shift which interconverts the products, was also located.
      Implicit solvent is observed to have a substantial effect of the course of the
      reaction, with the minimum energy path from the gas phase TS leading to (4 + 2)
      product whereas the DCM solvent phase TS leads to (4 + 3)-product. On the basis
      of these data it is suggested that a number of previously reported (4 + 3)
      cycloadditions may also possess reaction pathway bifurcations.

PMID- 29362752
TI  - Correction: High-temperature X-ray diffraction and thermal expansion of
      nanocrystalline and coarse-crystalline acanthite alpha-Ag2S and argentite beta
      Ag2S.
AB  - Correction for 'High-temperature X-ray diffraction and thermal expansion of
      nanocrystalline and coarse-crystalline acanthite alpha-Ag2S and argentite beta
      Ag2S' by S. I. Sadovnikov et al., Phys. Chem. Chem. Phys., 2016, 18, 4617-4626.

PMID- 29362753
TI  - Sensitive colorimetric immunoassay of Vibrio parahaemolyticus based on specific
      nonapeptide probe screening from a phage display library conjugated with MnO2
      nanosheets with peroxidase-like activity.
AB  - Pathogen detection continues to receive significant attention due to the harmful
      effects of pathogens on public health. Herein, specific nonapeptide-fusion
      proteins pVIII (pVIII fusion) were isolated from phage VQTVQIGSD (designated by
      the sequence of a fused foreign peptide), which was specifically screened from
      the f8/9 landscape phage library against Vibrio parahaemolyticus (V.
      parahaemolyticus) in a high-throughput way. The as-prepared V. parahaemolyticus
      specific recognition element is cheaper and more available than antibodies.
      Further, a highly sensitive colorimetric immunoassay for V. parahaemolyticus was
      established using pVIII fusion as capture probes coupled with protein-templated
      MnO2 nanosheets (NSs) as signal probes. In the presence of a target bacterium, V.
      parahaemolyticus, a sandwich-type complex of pVIII fusion-V. parahaemolyticus
      MnO2 NS@pVIII fusion was formed through specific recognition of pVIII fusion and
      V. parahaemolyticus. The signal probes (MnO2 NSs) could catalyze the reaction of
      3,3',5,5'-tetramethylbenzidine and H2O2 to generate a colorimetric change. The
      proposed V. parahaemolyticus detection method demonstrated a wide detection range
      (20-104 colony-forming units (CFU) mL-1), low limit of detection (15 CFU mL-1),
      excellent selectivity, and high reliability for real marine samples, showing
      potential application in marine microbiological detection and control.

PMID- 29362754
TI  - PLP-independent racemization: mechanistic and mutational studies of O
      ureidoserine racemase (DcsC).
AB  - O-Ureidoserine racemase (DcsC) is a PLP-independent enzyme in the biosynthetic
      route to the antibiotic d-cycloserine. Here we present the recombinant expression
      and characterization of a significantly more active DcsC variant featuring an N
      terminal SUMO-tag. Synthesis of enantiomeric pure inhibitors in combination with
      site-specific mutation of active site cysteines to serines of this enzyme offers
      closer insights into the mechanism of this transformation. Homology modelling
      with a close relative (diaminopimelate epimerase, DapF) inspired C- and N
      terminal truncation of DcsC to produce a more compact yet still active enzyme
      variant.

PMID- 29362755
TI  - The Piancatelli reaction and its variants: recent applications to high added
      value chemicals and biomass valorization.
AB  - The Piancatelli reaction, also called the Piancatelli rearrangement, consists in
      the direct conversion of furfuryl alcohols to cyclopentenone derivatives through
      a furan ring opening-electrocyclization process. Discovered in the late 70's,
      this reaction has been scarcely used for more than 40 years but recently has been
      the focus of particular interest from the scientific community and an increasing
      number of publications on the topic have emerged in the last few years. The first
      part of this review provides an overview of the recent achievements in classical
      Piancatelli reactions, discussing reaction conditions and catalytic systems,
      whereas the second part focuses on the variants recently developed, including the
      use of new nucleophiles in the process. Finally, the third part of this review
      deals with the recent application of this transformation to the production of
      commodity chemicals from renewable carbon feedstocks based on sugar-derived
      furanic platforms.

PMID- 29362756
TI  - Ultra-sensitive chemical and biological analysis via specialty fibers with built
      in microstructured optofluidic channels.
AB  - All-in-fiber optofluidics is an analytical tool that provides enhanced sensing
      performance with simplified analyzing system design. Currently, its advance is
      limited either by complicated liquid manipulation and light injection
      configuration or by low sensitivity resulting from inadequate light-matter
      interaction. In this work, we design and fabricate a side-channel photonic
      crystal fiber (SC-PCF) and exploit its versatile sensing capabilities in in-line
      optofluidic configurations. The built-in microfluidic channel of the SC-PCF
      enables strong light-matter interaction and easy lateral access of liquid samples
      in these analytical systems. In addition, the sensing performance of the SC-PCF
      is demonstrated with methylene blue for absorptive molecular detection and with
      human cardiac troponin T protein by utilizing a Sagnac interferometry
      configuration for ultra-sensitive and specific biomolecular specimen detection.
      Owing to the features of great flexibility and compactness, high-sensitivity to
      the analyte variation, and efficient liquid manipulation/replacement, the
      demonstrated SC-PCF offers a generic solution to be adapted to various fiber
      waveguide sensors to detect a wide range of analytes in real time, especially for
      applications from environmental monitoring to biological diagnosis.

PMID- 29362757
TI  - Syntheses, structures and theoretical calculations of stable triarylarsine
      radical cations.
AB  - The first stable triarylarsine radical cation salts 1+[BArF4]- and 2+[BArF4]-
      were afforded by one-electron oxidation of triarylarsines Trip3As (1, Trip =
      2,4,6-iPr3C6H2) and Dipp3As (2, Dipp = 2,6-iPr2C6H3) with AgSbF6 and NaBArF4 (ArF
      = 3,5-(CF3)2C6H3), respectively. Their molecular and electronic structures were
      investigated by single-crystal X-ray diffraction, electron paramagnetic resonance
      (EPR) and UV-vis absorption spectroscopy, in conjunction with density functional
      theory (DFT) calculations. The EPR and computational results demonstrate that the
      spin density of 1+ and 2+ is mainly distributed on the As nuclei.

PMID- 29362758
TI  - Free-electron-laser coherent diffraction images of individual drug-carrying
      liposome particles in solution.
AB  - Using the excellent performances of a SACLA (RIKEN/HARIMA, Japan) X-ray free
      electron laser (X-FEL), coherent diffraction imaging (CDI) was used to detect
      individual liposome particles in water, with or without inserted doxorubicin
      nanorods. This was possible because of the electron density differences between
      the carrier, the liposome, and the drug. The result is important since liposome
      nanocarriers at present dominate drug delivery systems. In spite of the low cross
      section of the original ingredients, the diffracted intensity of drug-free
      liposomes was sufficient for spatial reconstruction yielding quantitative
      structural information. For particles containing doxorubicin, the structural
      parameters of the nanorods could be extracted from CDI. Furthermore, the
      measurement of the electron density of the solution enclosed in each liposome
      provides direct evidence of the incorporation of ammonium sulphate into the
      nanorods. Overall, ours is an important test for extending the X-FEL analysis of
      individual nanoparticles to low cross-sectional systems in solution, and also for
      its potential use to optimize the manufacturing of drug nanocarriers.

PMID- 29362759
TI  - A simple microfluidic platform for the partial treatment of insuspendable tissue
      samples with orientation control.
AB  - Microfluidic devices have extensively been applied to study biological samples,
      including single cells. Exploiting laminar flows on a small scale, microfluidics
      allow for the selective and partial exposure of samples to various chemical
      treatments. Traditionally, suspendable samples are first flowed into formed
      microchannels and are allowed to adhere to the channel floor randomly with no
      control over sample placement or orientation, before being subjected to partial
      treatment. This severely limits the choice of samples and the extent of sample
      preparations. Here, we overcame this limit by reversing the sequence. We prepared
      the samples first on glass substrates. A patterned silicone slab was then placed
      on the substrate to form channels at an appropriate orientation with respect to
      the sample. We used liquid silicone rubber (LSR) as the base material. Its
      compliance (low elastic modulus) and its adhesion to glass offer the necessary
      seal to form the microchannels naturally. The applicability of the device was
      demonstrated by testing single axons of embryonic Drosophila motor neurons in
      vivo. A segment of the axons was subjected to drugs that inhibit myosin
      activities or block voltage-gated sodium ion channels. In response, the axons
      reduced the clustering of neuro-transmitter vesicles at the presynaptic terminal
      of neuromuscular junctions, or increased the calcium intake and underwent
      membrane hyperpolarization, respectively. Such fundamental studies cannot be
      carried out using conventional microfluidics.

PMID- 29362760
TI  - A comparison of the sensory and rheological properties of different cellulosic
      fibres for food.
AB  - The impact of different cellulosic microstructures formed by highly entangled
      fibre networks was studied for food applications as dietary fibre. This paper
      reports the impact of the microstructure on the rheological and sensory behaviour
      of the aqueous suspensions of particulate and fibrillated forms of softwood
      cellulosic fibres, and was compared with citrus fibres. An aqueous suspension of
      cellulosic fibres shows stable viscoelastic gel-like behaviour as a function of
      frequency. The particulate form of cellulosic fibres showed the lowest shear
      viscosity as compared with the entangled network system at comparable
      concentrations. To provide further insight into the relationship between the
      structure of cellulosic fibre and taste (salt) perception, an aqueous suspension
      with matched shear viscosities were studied. A hypothesis to explain why softwood
      cellulosic fibre (CTE) with an entangled network structure prolongs the taste
      perception is presented.

PMID- 29362761
TI  - Protein charge transfer absorption spectra: an intrinsic probe to monitor
      structural and oligomeric transitions in proteins.
AB  - Protein Charge Transfer Spectra (ProCharTS) originate when charged
      amino/carboxylate groups in the side chains of Lys/Glu act as electronic charge
      acceptors/donors for photoinduced charge transfer either from/to the polypeptide
      backbone or to each other. The absorption band intensities in ProCharTS at
      wavelengths of 250-800 nm are dependent on the 3D spatial proximity of these
      charged functional groups across the protein. Intrinsically disordered proteins
      (IDPs) are an important class of proteins involved in signalling and regulatory
      functions in the eukaryotic cell. IDPs are rich in charged amino acids, but lack
      structure-promoting intrinsic spectral probes like Tyr or Trp in their sequences,
      making their structural characterisation difficult. Here, we exploit the richness
      of charged amino acid populations among IDPs (like the PEST fragment of human c
      Myc, its mutant and dehydrin from maize) to sense structural transitions in IDPs
      using ProCharTS absorption spectra. Conformational changes induced in the protein
      by altering the pH and temperature of the aqueous medium were monitored by
      ProCharTS and confirmed by CD spectra. Further, the utility of ProCharTS to
      detect protein aggregation was examined using Hen Egg-White Lysozyme (HEWL)
      protein. The results revealed that in the presence of Trp/Tyr, ProCharTS
      absorbance was substantially reduced, specifically at wavelengths where the
      absorption by Trp or Tyr was near its maximum. Significant changes in the
      ProCharTS spectra were observed with changing pH in the range of 3-11, which
      correlated with changes in the secondary structure of the PEST fragment.
      Importantly, the absorbance at 280 nm, which is often employed as a measure of
      protein concentration, was profoundly altered by changes in ProCharTS intensity
      in response to changing the pH in dehydrin. The ProCharTS intensity was sensitive
      to temperature-induced changes in the secondary structures of the PEST fragments
      between 25-85  degrees C. The presence of 0.25 M NaCl or KCl in the medium also
      altered the ProCharTS spectrum. Finally, an increase in ProCharTS absorbance with
      time in HEWL at pH 2 directly correlated with the growth of HEWL aggregates and
      amyloid fibrils, as confirmed by the increasing thioflavin T fluorescence. Taken
      together, our work highlights the utility of ProCharTS as a label-free intrinsic
      probe to monitor changes in protein charge, structure and oligomeric state.

PMID- 29362762
TI  - Preparation of a BiVO4 nanoporous photoanode based on peroxovanadate reduction
      and conversion for efficient photoelectrochemical performance.
AB  - A unique, controllable and facile method based on peroxovanadate reduction and
      conversion to prepare BiVO4 nanoporous films is presented. In this method, a slow
      and controllable reduction of peroxovanadate with ethanol was used, which was the
      crucial step to ensure the uniform deposition of V2O5.xH2O on an F-doped tin
      oxide substrate, and subsequently the annealed V2O5.xH2O film was converted to a
      BiVO4 film by a simple impregnation method with Bi3+ under the oriented effect of
      polyethylene glycol. The converted BiVO4 film possessed a single monoclinic
      scheelite structure and exhibited an optimal water splitting photocurrent density
      of 1.10 mA cm-2 at 1.23 V vs. RHE in 0.1 M KH2PO4 (pH 7) under AM 1.5G
      illumination with an incident photon-to-current conversion efficiency of ~22.4%
      at 400 nm using an annealed V2O5.xH2O film deposited for 3 hours. The BiVO4 film
      also showed excellent water splitting performance and degradation efficiency in
      the PEC degradation of methylene blue and tetracycline hydrochloride with a rate
      constant of 0.63 h-1 and 0.21 h-1, respectively.

PMID- 29362763
TI  - Achieving selectivity for copper over zinc with luminescent terbium probes
      bearing phenanthridine antennas.
AB  - A family of terbium probes was synthesized and evaluated for the luminescence
      detection of copper and zinc in water at neutral pH. Each probe incorporates a
      terbium ion chelated by a macrocyclic polyaminocarboxylate and conjugated to
      either one, two, or three phenanthridine antennas via a diamine linker. All three
      probes, Tb-1Phen, Tb-2Phen, and Tb-3Phen, exhibit similar responses toward copper
      and zinc. In each case, the terbium-centered time-gated phosphorescence decreases
      upon binding either CuI or CuII but not upon addition of ZnII. The
      phosphorescence of Tb-2Phen is also not significantly affected by other metal
      ions including MgII, CaII, MnII, FeII, NiII, CdII, and HgII. Tb-1Phen, on the
      other hand, responds weakly to MnII, FeII and NiII. The lack of affinity of each
      probe for ZnII was further confirmed by competition experiments with CuI and
      CuII. Notably, whereas the terbium-centered emission of each probe is quenched
      upon copper coordination, the phenanthridine-centered luminescence emission is
      not. As such, each probe functions as a ratiometric probe for the selective
      detection of copper over zinc. Theoretical calculations further demonstrate that
      the turn off response of the probe is due to an increase in the distance
      separating the lanthanide ion from its phenanthridine antennas upon coordination
      of copper, which in turn decreases the efficiency of terbium sensitization by the
      phenanthridines.

PMID- 29362764
TI  - Total synthesis of pipecolic acid and 1-C-alkyl 1,5-iminopentitol derivatives by
      way of stereoselective aldol reactions from (S)-isoserinal.
AB  - A short synthesis of iminosugars and pipecolic acid derivatives has been realized
      through aldol addition of a pyruvate, a range of ketones and (S)-isoserinal,
      followed by catalytic reductive intramolecular amination. The stereoselective
      aldol reaction was achieved successfully by using tertiary amines or di-zinc
      aldol catalysts, thus constituting two parallel routes to optically pure products
      with good yields and high diastereoselectivities. These carbohydrate analogues
      may be the inhibitors of potent glycosidases and glycosyltransferases.

PMID- 29362765
TI  - Protective effects of a Ganoderma atrum polysaccharide against acrylamide induced
      oxidative damage via a mitochondria mediated intrinsic apoptotic pathway in IEC-6
      cells.
AB  - The preventive role of a purified Ganoderma atrum polysaccharide PSG-1-F2 as a
      new dietary antioxidant against the intestinal toxicity of acrylamide (ACR) was
      investigated in vitro. Our results showed that ACR could induce oxidative stress
      in IEC-6 cells by the overproduction of reactive oxygen species (ROS) and
      malondialdehyde (MDA), and as well as the reduction in the activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In addition, the
      induction of a mitochondria-mediated intrinsic apoptotic pathway by ACR was
      evidenced by the events of loss of mitochondrial membrane potential, bax/bcl-2
      dysregulation, cytochrome c release, and activation of caspase-3. Interestingly,
      PSG-1-F2 was able to suppress ACR toxicity by improving the redox status of IEC-6
      cells and by attenuating mitochondria-mediated apoptosis. Its protective effect
      was even superior to the clinically used antioxidant N-acetylcysteine (NAC). This
      study uniquely introduces PSG-1-F2 as a potential inhibitor of ACR-induced stress
      and toxicities.

PMID- 29362766
TI  - Effects of calorie restriction plus fish oil supplementation on abnormal
      metabolic characteristics and the iron status of middle-aged obese women.
AB  - The increasing prevalence of obesity and sedentary lifestyles has led to a higher
      incidence of metabolic syndrome (MetS) worldwide as well as in Taiwan. Middle
      aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular
      disease than men because they have more subcutaneous fat and larger waist
      circumferences compared with men with equal visceral fat levels. In this study,
      we investigated the effects of calorie restriction (CR) and fish oil
      supplementation (CRF) on middle-aged Taiwanese women with MetS. An open-label,
      parallel-arm, controlled trial was conducted for 12 weeks. A total of 75 eligible
      participants were randomly assigned to the CR or CRF group. Both the dietary
      intervention groups were further divided into two age groups: <=45 and >45 years.
      Changes in MetS severity, inflammatory status, iron status, and red blood cell
      fatty acid profile were evaluated. A total of 71 participants completed the
      trial. Both dietary interventions significantly ameliorated MetS and improved the
      participants' inflammatory status. CR significantly increased the total iron
      binding capacity (TIBC) whereas CRF increased hepcidin levels in women aged >45
      years. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic
      acid/docosahexaenoic acid ratios. Both interventions improved the anthropometric
      and MetS characteristics, including body weight, blood glucose and triglyceride
      levels, and the score of the homeostasis model assessment of insulin resistance
      and quantitative insulin sensitivity check index. In conclusion, the 12-week
      dietary interventions improved the abnormal metabolic status of middle-aged obese
      women. CRF was demonstrated to be more effective in ameliorating postprandial
      glucose level and TIBC in women aged >45 years than in those aged <=45 years.

PMID- 29362767
TI  - Capsaicin and nonivamide similarly modulate outcome measures of mitochondrial
      energy metabolism in HepG2 and 3T3-L1 cells.
AB  - Capsaicin, the highly pungent principle of red pepper, has been demonstrated to
      have anti-obesity properties by affecting energy and lipid metabolism. Recent
      evidence from human intervention trials shows that also less pungent capsaicin
      analogs, like nonivamide, may help to reduce total body fat, although mechanistic
      data comparing the effects of capsaicin and nonivamide on outcome measures of
      energy metabolism are lacking. Here, the tissue-specific effects of capsaicin and
      nonivamide on parameters of mitochondrial energy metabolism in 3T3-L1 and HepG2
      cells are investigated. Lipid accumulation was reduced to a similar extent after
      treatment with both test substances during the maturation of 3T3-L1 cells by up
      to 6.91% for capsaicin and up to 4.89% for nonivamide (p < 0.01) at a
      concentration of 0.1 MUM or 1 MUM, respectively. Energy-producing pathways, as
      indicated by the reduced mitochondrial oxygen consumption and reduced glucose and
      fatty acid uptake, were diminished after incubation with both capsaicinoids at a
      concentration of 100 MUM. The results from HPLC analyses revealed a reduced
      cellular energy charge potential after a 4 h treatment with nonivamide. In HepG2
      cells, similar effects were demonstrated: the glucose uptake was reduced by 18.7%
      and 25.8% (p < 0.05), after a 24 h incubation with 100 MUM capsaicin and
      nonivamide, respectively. In addition, the fatty acid uptake and oxygen
      consumption were decreased and the energy charge potential was diminished. These
      findings provide evidence that concentrations of capsaicin and nonivamide between
      0.1 and 100 MUM modulate the mechanisms of cellular energy metabolism to a
      similar extent, independent of the investigated tissue.

PMID- 29362768
TI  - Enhanced green upconversion luminescence in tetrahedral LiYF4:Yb/Er nanoparticles
      by manganese(ii)-doping: the key role of the host lattice.
AB  - We report the enhancement of green upconversion luminescence in tetrahedral
      LiYF4:Yb/Er nanoparticles by Mn2+ ion doping, which is different from the
      enhanced single-band red emission dominated by Mn2+ ions in cubic NaLnF4:Yb/Er
      (Ln = Y, Gd, Lu) nanoparticles. The energy levels of the first excited state 4T1
      of Mn2+ in tetrahedral LiYF4:Gd and cubic NaGd(Y)F4 are compared by detection of
      emissions from Mn2+via the energy transition from Gd3+ to Mn2+ with excitation at
      275 nm. The coordination environments of Mn2+ in these two host lattices have
      been investigated by X-ray absorption fine structure measurements. The results
      demonstrate that the formation of tetrahedral MnF4 in tetragonal LiYF4 arising
      from the replacement of Ln3+ ions with Mn2+ ions leads to a higher energy level
      of the Mn2+ 4T1 state than that in octahedral MnF6 in cubic NaYF4. The high-lying
      excited state of tetrahedral MnF4 is close to the green emitting 4S3/2 state of
      Er3+ and thus enhances green upconversion emission in tetragonal LiYF4:Yb/Er,
      while the low-lying excited state of octahedral MnF6 dominates red emission in
      cubic NaYF4:Yb/Er. These findings provide direct evidence for the key roles of
      the host lattices and more possibilities in modulating the upconversion behaviour
      of lanthanide-based nanoparticles by transition-metal ion doping to achieve the
      desired goals of specific applications.

PMID- 29362769
TI  - E-Z isomerization in Suzuki cross-couplings of haloenones: ligand effects and
      evidence for a separate catalytic cycle.
AB  - Suzuki cross-coupling of haloalkenes is generally assumed to occur with retention
      of the alkene stereochemistry. While studying Suzuki cross-couplings on E-1,2
      dichlorovinyl phenyl ketone, we were surprised to observe extensive
      isomerization. More surprisingly, the ligand employed strongly influenced the
      degree of isomerization: DPEphos and Xantphos led to 96% isomerized cross-coupled
      product whereas reactions in the absence of a phosphine ligand, or reactions
      employing t-BuXantphos, gave 94% retention of stereochemistry. While E-Z
      isomerization in Pd-catalyzed vinylic couplings has previously been attributed to
      events within the cross-coupling catalytic cycle, we present experimental and
      computational evidence for a separate Pd-catalyzed isomerization process in these
      reactions.

PMID- 29362770
TI  - Changing the Subject: The Place of Revisions in Grammatical Development.
AB  - Purpose: This article focuses on toddlers' revisions of the sentence subject and
      tests the hypothesis that subject diversity (i.e., the number of different
      subjects produced) increases the probability of subject revision. Method: One
      hour language samples were collected from 61 children (32 girls) at 27 months.
      Spontaneously produced, active declarative sentences (ADSs) were analyzed for
      subject diversity and the presence of subject revision and repetition. The number
      of different words produced, mean length of utterance, tense/agreement
      productivity score, and the number of ADSs were also measured. Results:
      Regression analyses were performed with revision and repetition as the dependent
      variables. Subject diversity significantly predicted the probability of revision,
      whereas the number of ADSs predicted the probability of repetition. Conclusion:
      The results support the hypothesis that subject diversity increases the
      probability of subject revision. It is proposed that lexical diversity within
      specific syntactic positions is the primary mechanism whereby revision rates
      increase with grammatical development. The results underscore the need to
      differentiate repetition from revision in the classification of disfluencies.

PMID- 29362771
TI  - Orpheus' Descent Into the Neurointensive Care Unit.

PMID- 29362772
TI  - Pharma Art-Abstract Medication in the Work of Beverly Fishman.

PMID- 29362773
TI  - Nystagmus and Platinum Hair.

PMID- 29362774
TI  - Left Atrial Appendage Occlusion During Cardiac Operations for Prevention of
      Thromboembolic Events.

PMID- 29362775
TI  - Three Decades of Peer Review Congresses.

PMID- 29362776
TI  - Evaluating the Long-term Safety of Hysteroscopic Sterilization.

PMID- 29362777
TI  - A Window Into the Evolution of Trauma-Focused Psychotherapies for Posttraumatic
      Stress Disorder.

PMID- 29362779
TI  - Tick Bite Linked to Red Meat Allergy.

PMID- 29362778
TI  - Oral Medications to Treat Toenail Fungal Infection.
AB  - Clinical Question: Which oral antifungal medication is associated with the
      highest clinical (ie, normal appearance of the toenail) and mycological (negative
      culture, microscopy, or both) cure rates vs placebo or other antifungals when
      used to treat fungal infections? Bottom Line: Both terbinafine and azole-based
      medications were associated with higher clinical and mycological cure rates
      compared with placebo (high-quality evidence). Azoles were associated with lower
      cure rates than terbinafine when compared directly.

PMID- 29362780
TI  - CMS Cancels Mandatory Hip and Cardiac Payment Bundles.

PMID- 29362781
TI  - Study Recruitment to Accelerate Precision Medicine.

PMID- 29362783
TI  - Predetermination of Sex.

PMID- 29362784
TI  - Trialists' Intent to Share Individual Participant Data as Disclosed at
      ClinicalTrials.gov.

PMID- 29362785
TI  - Editorial Evaluation, Peer Review, and Publication of Research Reports With and
      Without Supplementary Online Content.

PMID- 29362786
TI  - Characteristics of Interim Publications of Randomized Clinical Trials and
      Comparison With Final Publications.

PMID- 29362787
TI  - Prevalence of Disclosed Conflicts of Interest in Biomedical Research and
      Associations With Journal Impact Factors and Altmetric Scores.

PMID- 29362788
TI  - Altmetric Scores, Citations, and Publication of Studies Posted as Preprints.

PMID- 29362789
TI  - Shantanu Nundy, MD: The Human Diagnosis Project.

PMID- 29362791
TI  - Social Media Intervention Improves Vaccine Acceptance.

PMID- 29362790
TI  - New Combination Therapy for Cystic Fibrosis.

PMID- 29362792
TI  - Bariatric Surgery Controls Blood Pressure.

PMID- 29362793
TI  - Opioid Agonist and Antagonist Therapies Prevent Opioid Relapse.

PMID- 29362794
TI  - Association Between Left Atrial Appendage Occlusion and Readmission for
      Thromboembolism Among Patients With Atrial Fibrillation Undergoing Concomitant
      Cardiac Surgery.
AB  - Importance: The left atrial appendage is a key site of thrombus formation in
      atrial fibrillation (AF) and can be occluded or removed at the time of cardiac
      surgery. There is limited evidence regarding the effectiveness of surgical left
      atrial appendage occlusion (S-LAAO) for reducing the risk of thromboembolism.
      Objective: To evaluate the association of S-LAAO vs no receipt of S-LAAO with the
      risk of thromboembolism among older patients undergoing cardiac surgery. Design,
      Setting, and Participants: Retrospective cohort study of a nationally
      representative Medicare-linked cohort from the Society of Thoracic Surgeons Adult
      Cardiac Surgery Database (2011-2012). Patients aged 65 years and older with AF
      undergoing cardiac surgery (coronary artery bypass grafting [CABG], mitral valve
      surgery with or without CABG, or aortic valve surgery with or without CABG) with
      and without concomitant S-LAAO were followed up until December 31, 2014.
      Exposures: S-LAAO vs no S-LAAO. Main Outcomes and Measures: The primary outcome
      was readmission for thromboembolism (stroke, transient ischemic attack, or
      systemic embolism) at up to 3 years of follow-up, as defined by Medicare claims
      data. Secondary end points included hemorrhagic stroke, all-cause mortality, and
      a composite end point (thromboembolism, hemorrhagic stroke, or all-cause
      mortality). Results: Among 10 524 patients undergoing surgery (median age, 76
      years; 39% female; median CHA2DS2-VASc score, 4), 3892 (37%) underwent S-LAAO.
      Overall, at a mean follow-up of 2.6 years, thromboembolism occurred in 5.4%,
      hemorrhagic stroke in 0.9%, all-cause mortality in 21.5%, and the composite end
      point in 25.7%. S-LAAO, compared with no S-LAAO, was associated with lower
      unadjusted rates of thromboembolism (4.2% vs 6.2%), all-cause mortality (17.3% vs
      23.9%), and the composite end point (20.5% vs 28.7%) but no significant
      difference in rates of hemorrhagic stroke (0.9% vs 0.9%). After inverse
      probability-weighted adjustment, S-LAAO was associated with a significantly lower
      rate of thromboembolism (subdistribution hazard ratio [HR], 0.67; 95% CI, 0.56
      0.81; P < .001), all-cause mortality (HR, 0.88; 95% CI, 0.79-0.97; P = .001), and
      the composite end point (HR, 0.83; 95% CI, 0.76-0.91; P < .001) but not
      hemorrhagic stroke (subdistribution HR, 0.84; 95% CI, 0.53-1.32; P = .44). S
      LAAO, compared with no S-LAAO, was associated with a lower risk of
      thromboembolism among patients discharged without anticoagulation (unadjusted
      rate, 4.2% vs 6.0%; adjusted subdistribution HR, 0.26; 95% CI, 0.17-0.40; P <
      .001), but not among patients discharged with anticoagulation (unadjusted rate,
      4.1% vs 6.3%; adjusted subdistribution HR, 0.88; 95% CI, 0.56-1.39; P = .59).
      Conclusions and Relevance: Among older patients with AF undergoing concomitant
      cardiac surgery, S-LAAO, compared with no S-LAAO, was associated with a lower
      risk of readmission for thromboembolism over 3 years. These findings support the
      use of S-LAAO, but randomized trials are necessary to provide definitive
      evidence.

PMID- 29362795
TI  - Effect of Prolonged Exposure Therapy Delivered Over 2 Weeks vs 8 Weeks vs Present
      Centered Therapy on PTSD Symptom Severity in Military Personnel: A Randomized
      Clinical Trial.
AB  - Importance: Effective and efficient treatment is needed for posttraumatic stress
      disorder (PTSD) in active duty military personnel. Objective: To examine the
      effects of massed prolonged exposure therapy (massed therapy), spaced prolonged
      exposure therapy (spaced therapy), present-centered therapy (PCT), and a minimal
      contact control (MCC) on PTSD severity. Design, Setting, and Participants:
      Randomized clinical trial conducted at Fort Hood, Texas, from January 2011
      through July 2016 and enrolling 370 military personnel with PTSD who had returned
      from Iraq, Afghanistan, or both. Final follow-up was July 11, 2016.
      Interventions: Prolonged exposure therapy, cognitive behavioral therapy involving
      exposure to trauma memories/reminders, administered as massed therapy (n = 110;
      10 sessions over 2 weeks) or spaced therapy (n = 109; 10 sessions over 8 weeks);
      PCT, a non-trauma-focused therapy involving identifying/discussing daily
      stressors (n = 107; 10 sessions over 8 weeks); or MCC, telephone calls from
      therapists (n = 40; once weekly for 4 weeks). Main Outcomes and Measures:
      Outcomes were assessed before and after treatment and at 2-week, 12-week, and 6
      month follow-up. Primary outcome was interviewer-assessed PTSD symptom severity,
      measured by the PTSD Symptom Scale-Interview (PSS-I; range, 0-51; higher scores
      indicate greater PTSD severity; MCID, 3.18), used to assess efficacy of massed
      therapy at 2 weeks posttreatment vs MCC at week 4; noninferiority of massed
      therapy vs spaced therapy at 2 weeks and 12 weeks posttreatment (noninferiority
      margin, 50% [2.3 points on PSS-I, with 1-sided alpha = .05]); and efficacy of
      spaced therapy vs PCT at posttreatment. Results: Among 370 randomized
      participants, data were analyzed for 366 (mean age, 32.7 [SD, 7.3] years; 44
      women [12.0%]; mean baseline PSS-I score, 25.49 [6.36]), and 216 (59.0%)
      completed the study. At 2 weeks posttreatment, mean PSS-I score was 17.62 (mean
      decrease from baseline, 7.13) for massed therapy and 21.41 (mean decrease, 3.43)
      for MCC (difference in decrease, 3.70 [95% CI,0.72 to 6.68]; P = .02). At 2 weeks
      posttreatment, mean PSS-I score was 18.03 for spaced therapy (decrease, 7.29;
      difference in means vs massed therapy, 0.79 [1-sided 95% CI, -infinity to 2.29; P
      = .049 for noninferiority]) and at 12 weeks posttreatment was 18.88 for massed
      therapy (decrease, 6.32) and 18.34 for spaced therapy (decrease, 6.97;
      difference, 0.55 [1-sided 95% CI, -infinity to 2.05; P = .03 for
      noninferiority]). At posttreatment, PSS-I scores for PCT were 18.65 (decrease,
      7.31; difference in decrease vs spaced therapy, 0.10 [95% CI, -2.48 to 2.27]; P =
      .93). Conclusions and Relevance: Among active duty military personnel with PTSD,
      massed therapy (10 sessions over 2 weeks) reduced PTSD symptom severity more than
      MCC at 2-week follow-up and was noninferior to spaced therapy (10 sessions over 8
      weeks), and there was no significant difference between spaced therapy and PCT.
      The reductions in PTSD symptom severity with all treatments were relatively
      modest, suggesting that further research is needed to determine the clinical
      importance of these findings. Trial Registration: clinicaltrials.gov Identifier:
      NCT01049516.

PMID- 29362797
TI  - Patellofemoral Pain.

PMID- 29362796
TI  - Association of Hysteroscopic vs Laparoscopic Sterilization With Procedural,
      Gynecological, and Medical Outcomes.
AB  - Importance: Safety of hysteroscopic sterilization has been recently questioned
      following reports of general symptoms such as allergy, tiredness, and depression
      in addition to associated gynecological results such as pelvic pain, perforation
      of fallopian tubes or uterus, and unwanted pregnancy. Objective: To compare the
      risk of reported adverse events between hysteroscopic and laparoscopic
      sterilization. Design, Setting, and Participants: French nationwide cohort study
      using the national hospital discharge database linked to the health insurance
      claims database. Women aged 30 to 54 years receiving a first hysteroscopic or
      laparoscopic sterilization between 2010 and 2014 were included and were followed
      up through December 2015. Exposures: Hysteroscopic sterilization vs laparoscopic
      sterilization. Main Outcomes and Measures: Risks of procedural complications
      (surgical and medical) and of gynecological (sterilization failure that includes
      salpingectomy, second sterilization procedure, or pregnancy; pregnancy;
      reoperation) and medical outcomes (all types of allergy; autoimmune diseases;
      thyroid disorder; use of analgesics, antimigraines, antidepressants,
      benzodiazepines; outpatient visits; sickness absence; suicide attempts; death)
      that occurred within 1 and 3 years after sterilization were compared using
      inverse probability of treatment-weighted Cox models. Results: Of the 105 357
      women included (95.5% of eligible participants; mean age, 41.3 years [SD, 3.7
      years]), 71 303 (67.7% ) underwent hysteroscopic sterilization, and 34 054
      (32.3%) underwent laparoscopic sterilization. During the hospitalization for
      sterilization, risk of surgical complications for hysteroscopic sterilization was
      lower: 0.13% for hysteroscopic sterilization vs 0.78% for laparoscopic
      sterilization (adjusted risk difference [RD], -0.64; 95% CI, -0.67 to -0.60) and
      was lower for medical complications: 0.06% vs 0.11% (adjusted RD, -0.05; 95% CI, 
      0.08 to -0.01). During the first year after sterilization, 4.83% of women who
      underwent hysteroscopic sterilization had a higher risk of sterilization failure
      than the 0.69% who underwent laparoscopic sterilization (adjusted hazard ratio
      [HR], 7.11; 95% CI, 5.92 to 8.54; adjusted RD, 4.23 per 100 person-years; 95% CI,
      3.40 to 5.22). Additionally, 5.65% of women who underwent hysteroscopic
      sterilization required gynecological reoperation vs 1.76% of women who underwent
      laparoscopic sterilization (adjusted HR, 3.26; 95% CI, 2.90 to 3.67; adjusted RD,
      4.63 per 100 person-years; 95% CI, 3.38 to 4.75); these differences persisted
      after 3 years, although attenuated. Hysteroscopic sterilization was associated
      with a lower risk of pregnancy within the first year of the procedure but was not
      significantly associated with a difference in risk of pregnancy by the third year
      (adjusted HR, 1.04; 95% CI, 0.83-1.30; adjusted RD, 0.01 per 100 person-years;
      95% CI, -0.04 to 0.07). Risks of medical outcomes were not significantly
      increased with hysteroscopic sterilization compared with laparoscopic
      sterilization. Conclusions and Relevance: Among women undergoing first
      sterilization, the use of hysteroscopic sterilization was significantly
      associated with higher risk of gynecological complications over 1 year and over 3
      years than was laparoscopic sterilization. Risk of medical outcomes was not
      significantly increased over 1 year or over 3 years. These findings do not
      support increased medical risks associated with hysteroscopic sterilization.

PMID- 29362799
TI  - The Things We Say.

PMID- 29362802
TI  - Possible Racial Disparities in NICU Breast Milk Use.

PMID- 29362800
TI  - Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic
      Test Accuracy Studies: The PRISMA-DTA Statement.
AB  - Importance: Systematic reviews of diagnostic test accuracy synthesize data from
      primary diagnostic studies that have evaluated the accuracy of 1 or more index
      tests against a reference standard, provide estimates of test performance, allow
      comparisons of the accuracy of different tests, and facilitate the identification
      of sources of variability in test accuracy. Objective: To develop the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagnostic test
      accuracy guideline as a stand-alone extension of the PRISMA statement.
      Modifications to the PRISMA statement reflect the specific requirements for
      reporting of systematic reviews and meta-analyses of diagnostic test accuracy
      studies and the abstracts for these reviews. Design: Established standards from
      the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network
      were followed for the development of the guideline. The original PRISMA statement
      was used as a framework on which to modify and add items. A group of 24
      multidisciplinary experts used a systematic review of articles on existing
      reporting guidelines and methods, a 3-round Delphi process, a consensus meeting,
      pilot testing, and iterative refinement to develop the PRISMA diagnostic test
      accuracy guideline. The final version of the PRISMA diagnostic test accuracy
      guideline checklist was approved by the group. Findings: The systematic review
      (produced 64 items) and the Delphi process (provided feedback on 7 proposed
      items; 1 item was later split into 2 items) identified 71 potentially relevant
      items for consideration. The Delphi process reduced these to 60 items that were
      discussed at the consensus meeting. Following the meeting, pilot testing and
      iterative feedback were used to generate the 27-item PRISMA diagnostic test
      accuracy checklist. To reflect specific or optimal contemporary systematic review
      methods for diagnostic test accuracy, 8 of the 27 original PRISMA items were left
      unchanged, 17 were modified, 2 were added, and 2 were omitted. Conclusions and
      Relevance: The 27-item PRISMA diagnostic test accuracy checklist provides
      specific guidance for reporting of systematic reviews. The PRISMA diagnostic test
      accuracy guideline can facilitate the transparent reporting of reviews, and may
      assist in the evaluation of validity and applicability, enhance replicability of
      reviews, and make the results from systematic reviews of diagnostic test accuracy
      studies more useful.

PMID- 29362803
TI  - African Countries Move Closer to Eradicating Guinea Worm Disease.

PMID- 29362804
TI  - Interocular correlation sensitivity and its relationship with stereopsis.
AB  - Stereoscopic vision uses the disparity between the images received by the two
      eyes to derive three-dimensional estimates. Here, we were interested in providing
      a measure of the strength of binocular vision alternate to disparity processing.
      In particular, we wanted to assess the spatial dependence of sensitivity to
      detect interocular correlation (IOC). Thus we designed dichoptic stimuli composed
      of bandpass textures whose IOC is sinusoidally modulated at different correlation
      frequencies and compared sensitivity to these stimuli to that of analogous
      stimuli modulated in disparity. We observed that the IOC sensitivity is low
      pass/band pass and increases with stimulus duration and contrast in a similar way
      to that of disparity sensitivity. IOC sensitivity is only weakly, though
      significantly, correlated with disparity sensitivity in the population. It could
      provide an alternate measure of binocular sensitivity.

PMID- 29362805
TI  - The edge of awareness: Mask spatial density, but not color, determines optimal
      temporal frequency for continuous flash suppression.
AB  - The study of how visual processing functions in the absence of visual awareness
      has become a major research interest in the vision-science community. One of the
      main sources of evidence that stimuli that do not reach conscious awareness-and
      are thus "invisible"-are still processed to some degree by the visual system
      comes from studies using continuous flash suppression (CFS). Why and how CFS
      works may provide more general insight into how stimuli access awareness. As
      spatial and temporal properties of stimuli are major determinants of visual
      perception, we hypothesized that these properties of the CFS masks would be of
      significant importance to the achieved suppression depth. In previous studies
      however, the spatial and temporal properties of the masks themselves have
      received little study, and masking parameters vary widely across studies, making
      a metacomparison difficult. To investigate the factors that determine the
      effectiveness of CFS, we varied both the temporal frequency and the spatial
      density of Mondrian-style masks. We consistently found the longest suppression
      duration for a mask temporal frequency of around 6 Hz. In trials using masks with
      reduced spatial density, suppression was weaker and frequency tuning was less
      precise. In contrast, removing color reduced mask effectiveness but did not
      change the pattern of suppression strength as a function of frequency. Overall,
      this pattern of results stresses the importance of CFS mask parameters and is
      consistent with the idea that CFS works by disrupting the spatiotemporal
      mechanisms that underlie conscious access to visual input.

PMID- 29362806
TI  - Transsaccadic transfer of distortion adaptation in a natural environment.
AB  - Spatially varying distortions in optical elements-for instance prisms and
      progressive power lenses-modulate the visual world disparately in different
      visual areas. Saccadic eye movements in such a complexly distorted environment
      thereby continuously alter the retinal location of the distortions. Yet the
      visual system achieves perceptual constancy by compensating for distortions
      irrespective of their retinal relocations at different fixations. Here, we
      assessed whether the visual system retains its plasticity to distortions across
      saccades to attain stability. Specifically, we tapped into reference frames of
      geometric skew-adaptation aftereffects to evaluate the transfer of retinotopic
      and spatiotopic distortion information across saccades. Adaptation to skew
      distortion of natural-image content was tested at retinotopic and spatiotopic
      locations after a saccade was executed between adaptation and test phases. The
      skew-adaptation information was partially transferred to a new fixation after a
      saccade. Significant adaptation aftereffects were obtained at both retinotopic
      and spatiotopic locations. Conceivably, spatiotopic information was used to
      counterbalance the saccadic retinal shifts of the distortions. Therefore,
      distortion processing in a natural visual world does not start anew at each
      fixation; rather, retinotopic and spatiotopic skew information acquired at
      previous fixations are preserved to mediate stable perception during eye
      movements.

PMID- 29362807
TI  - Shatter and splatter: The contribution of mechanical and optical properties to
      the perception of soft and hard breaking materials.
AB  - Research on the visual perception of materials has mostly focused on the surface
      qualities of rigid objects. The perception of substance like materials is less
      explored. Here, we investigated the contribution of, and interaction between,
      surface optics and mechanical properties to the perception of nonrigid, breaking
      materials. We created novel animations of materials ranging from soft to hard
      bodies that broke apart differently when dropped. In Experiment 1, animations
      were rendered as point-light movies varying in dot density, as well as "full-cue"
      optical versions ranging from translucent glossy to opaque matte under a natural
      illumination field. Observers used a scale to rate each substance on different
      attributes. In Experiment 2 we investigated how much shape contributed to ratings
      of the full-cue stimuli in Experiment 1, by comparing ratings when observers were
      shown movies versus one frame of the animation. The results showed that optical
      and mechanical properties had an interactive effect on ratings of several
      material attributes. We also found that motion and static cues each provided a
      lot of information about the material qualities; however, when combined, they
      influenced observers' ratings interactively. For example, in some conditions,
      motion dominated over optical information; in other conditions, it enhanced the
      effect of optics. Our results suggest that rating multiple attributes is an
      effective way to measure underlying perceptual differences between nonrigid
      breaking materials, and this study is the first to our knowledge to show
      interactions between optical and mechanical properties in a task involving
      judgments of perceptual qualities.

PMID- 29362809
TI  - An Erythematous-squamous Lesion of the Foot: A Quiz.

PMID- 29362808
TI  - Stimulus conflation and tuning selectivity in V4 neurons: a model of visual
      crowding.
AB  - Visual crowding is a fundamental constraint on our ability to identify peripheral
      objects in cluttered environments. This study proposes a descriptive model for
      understanding crowding based on the tuning selectivity for stimuli within the
      receptive field (RF) and examines potential neural correlates in cortical area
      V4. For V4 neurons, optimally sized, letter-like stimuli are much smaller than
      the RF. This permits stimulus conflation, the fusing of separate objects into a
      single identity, to occur within the RF of single neurons. Flanking interactions
      between such stimuli were found to be limited to the RF. The response to an
      optimal stimulus centered in the neuron's RF, is suppressed by the simultaneous
      presentation of flanking stimuli within the RF. The degree of suppression is a
      function of the neuron's stimulus tuning properties and the position of the
      flanker within the RF. A single neuron may show suppression or facilitation
      depending on the detailed stimulus conditions and the relationship to tuning
      selectivity. Loss of activity in the set of neurons tuned to a particular
      stimulus alters its overall representation and potential identification, thus
      forming a basis for visual crowding effects. The mechanisms that determine the
      outcome of conflation are associated with object identification, and are not some
      other independent visual phenomena.

PMID- 29362810
TI  - Predictive Model for Response Rate to Narrowband Ultraviolet B Phototherapy in
      Vitiligo: A Retrospective Cohort Study of 579 Patients.
AB  - Vitiligo is an acquired depigmenting disorder. To date, there is no predictive
      model for its response rate to narrowband ultraviolet B (NBUVB) phototherapy. The
      aim of this study was to investigate the different types of response of patients
      with non-segmental vitiligo undergoing NBUVB 3 times a week. Many patients who
      were previously considered non-responders were given the opportunity to continue
      the treatment. Long-term maintenance of treatment and follow-up of a cohort of
      579 patients enabled different subtypes of response (very rapid, rapid, average,
      slow and "non-responders") to be described for the first time, and a predictive
      model of response to be constructed based on repigmentation rate in the first 48
      sessions of NBUVB. Among those patients who did not respond during the first 48
      sessions, a new subgroup of patients was found, termed "very-slow" responders,
      who achieved a low, but significant, level of repigmentation after 96 sessions of
      NBUVB.

PMID- 29362811
TI  - Efficacy of Omalizumab Treatment with Concomitant Antihistamines as Needed for
      Moderate, Refractory Chronic Spontaneous Urticaria.

PMID- 29362812
TI  - Banded Scalp Hair with an Unusual Glistening Appearance in a Teenager: A Quiz.

PMID- 29362813
TI  - Two Severe Cases of Adult-onset Still's Disease with Persistent Pruritic
      Eruptions.

PMID- 29362814
TI  - Longer Duration of Untreated Psychosis is Associated with Poorer Outcomes for
      Patients with Delusional Infestation.
AB  - We examined the association between the duration of untreated psychosis and
      outcome for patients with delusional infestation. This multi-centre international
      study included 211 consecutive patients. Illness severity was evaluated at first
      presentation and outcome was measured with the Clinical Global Impression scale
      (CGI) at baseline and follow-up. A regression analysis showed a clear clinical
      and statistically significant association between shorter duration of untreated
      psychosis and better outcome at follow-up. Patients with a duration of untreated
      psychosis of less than one year showed a CGI-S change from 5.37 to 2.07; those
      with a duration of untreated psychosis of 1-5 years a change from 5.48 to 2.59,
      and those with a duration of untreated psychosis of >5 years a change from 5.59
      to 3.37. This difference of 1.1 CGI points between the groups resembles a
      clinically relevant difference in patient outcome. Our results suggest that
      longer duration of untreated psychosis in patients with delusional infestation is
      associated with significantly less favour-able clinical outcomes.

PMID- 29362815
TI  - Two Minimal Clinically Important Difference (2MCID): A New Twist on an Old
      Concept.

PMID- 29362816
TI  - Pyoderma Gangrenosum Under Dabrafenib and Trametinib for Metastatic Melanoma.

PMID- 29362817
TI  - [Superior canal dehiscence syndrome : Diagnosis with vestibular evoked myogenic
      potentials and fremitus nystagmus. German version].
AB  - BACKGROUND: Superior canal dehiscence syndrome (SCDS) is a relatively rare
      neurotological disorder that is characterized by a heterogeneous clinical
      picture. Recently, vestibular evoked myogenic potential (VEMP) measurementwas
      established for the diagnosis of SCDS. In the present study, a case series of
      patients with SCDS were analyzed, with a focus on VEMP. METHODS: Four patients
      with SCDS were prospectively examined with ocular VEMP (oVEMP) and cervical VEMP
      (cVEMP). The clinical features and the standard audiovestibular test battery
      results are summarized and analyzed. The diagnostic accuracy of VEMP testing is
      evaluated. RESULTS: The increased oVEMP amplitudes had a specificity of 100% in
      this patient population. All patients had normal caloric function and head
      impulse testing. The Tullio sign was observed in two patients. Three patients had
      autophony. The airbone gap was not greater than 10 dB in any of the patients. Two
      patients had marked fremitus nystagmus. All patients had a bony dehiscence of the
      superior semicircular canal on computed tomography imaging. CONCLUSION: The
      subjective and clinical features in this case series of SCDS patients were
      heterogeneous. However, objective oVEMP testing had the highest diagnostic value.
      Furthermore, we describe a new diagnostic clinical sign: fremitus nystagmus.

PMID- 29362818
TI  - Traumatic cardiac luxation.

PMID- 29362819
TI  - A comparison of group sequential and fixed sample size designs for bioequivalence
      trials with highly variable drugs.
AB  - PURPOSE: A drug is defined as highly variable if its intra-individual coefficient
      of variation (CV) is greater than or equal to 30%. In such a case, bioequivalence
      may be assessed by means of methods that take the (high) variability into
      account. The Scaled Average Bioequivalence (SABE) approach is such a procedure
      and represents the recommendations of FDA. The aim of this investigation is to
      compare the performance characteristics of classical group sequential designs
      (GSD) and fixed design settings for three-period crossover bioequivalence studies
      with highly variable drugs, where the SABE procedure is utilized. METHODS: Monte
      Carlo simulations were performed to assess type I error rate, power, and average
      sample size for GSDs with Pocock's and O'Brien-Fleming's stopping rules and
      various timings of the interim analysis and for fixed design settings. RESULTS:
      Based on our investigated scenarios, the GSDs show comparable properties with
      regard to power and type I error rate as compared to the corresponding fixed
      designs. However, due to an advantage in average sample size, the most appealing
      design is Pocock's approach with interim analysis after 50% information fraction.
      CONCLUSIONS: Due to their favorable performance characteristics, two-stage GSDs
      are an appealing alternative to fixed sample designs when assessing
      bioequivalence in highly variable drugs.

PMID- 29362820
TI  - Subtherapeutic valproic acid plasma concentrations under concomitant dipyrone
      therapy in an epilepsy patient-a case report.

PMID- 29362822
TI  - Gut Microbiota and IGF-1.
AB  - Microbiota and their hosts have coevolved for millions of years. Microbiota are
      not only critical for optimal development of the host under normal physiological
      growth, but also important to ensure proper host development during nutrient
      scarcity or disease conditions. A large body of research has begun to detail the
      mechanism(s) of how microbiota cooperate with the host to maintain optimal health
      status. One crucial host pathway recently demonstrated to be modulated by
      microbiota is that of the growth factor insulin like growth factor 1 (IGF-1). Gut
      microbiota are capable of dynamically modulating circulating IGF-1 in the host,
      with the majority of data suggesting that microbiota induce host IGF-1 synthesis
      to influence growth. Microbiota-derived metabolites such as short chain fatty
      acids are sufficient to induce IGF-1. Whether microbiota induction of IGF-1 is
      mediated by the difference in growth hormone expression or the host sensitivity
      to growth hormone is still under investigation. This review summarizes the
      current data detailing the interaction between gut microbiota, IGF-1 and host
      development.

PMID- 29362823
TI  - Exposure Duration Is a Determinant of the Effect of Sinusoidal Electromagnetic
      Fields on Peak Bone Mass of Young Rats.
AB  - We proposed a three-step strategy to obtain the optimal therapeutic parameters,
      which is composed of large-scale screening at cellular level, verification in
      animal experiments, and confirmation by a clinical trial. The objective of the
      current study was to test the feasibility of our strategy. Newborn rat calvarial
      osteoblasts were treated by 50 Hz 1.8 mT sinusoidal electromagnetic fields
      (SEMFs) with 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 h/days, respectively. The
      osteogenic differentiation and maturation of the osteoblast were assayed and
      compared to obtain the optimal duration. One-month-old growing rats were then
      treated by the same SEMFs with 0.5, 1.5, and 2.5 h/days, respectively, and the
      peak bone mass was analyzed after 2 months. It was found that the optimal
      exposure duration to promote the osteogenic differentiation and maturation of
      osteoblasts was 1.5 h/days, judging by the increasing degrees of ALP activity,
      calcified nodules formed, the gene and protein expression levels of Runx-2, BMP
      2, and Col-I, as well as the expression levels of signaling proteins of the BMP
      2/Smad1/5/8 pathway. The highest increase of peak bone mass after 2 months was
      also obtained by 1.5 h/days, judging by the results of X-ray dual-energy
      absorptiometry, mechanical property analysis, micro-CT scanning, and serum bone
      turnover marker examinations. The above results indicated that exposure duration
      is a determinant for the therapeutic effect of EMFs, and the optimal therapeutic
      effects only can be obtained by the optimal exposure duration.

PMID- 29362824
TI  - Time-course responses of ileal and fecal microbiota and metabolite profiles to
      antibiotics in cannulated pigs.
AB  - We investigated the time-course effects of therapeutic antibiotics on intestinal
      microbial composition and metabolism in an ileal-cannulated pig model. Sixteen
      ileal-cannulated piglets (12 +/- 0.5 kg) were assigned to two groups (n = 8) and
      fed standard diets with or without antibiotics. At 4 days before, and at days 2,
      7, and 13 after antibiotic administration, ileal and fecal samples were collected
      for analysis of microbiota composition via 16S rRNA MiSeq sequencing and
      metabolites (short-chain fatty acids, biogenic amines, and indole). It was found
      that Lactobacillus and Bifidobacterium had decreased by an average 2.68-fold and
      508-fold in ileum on days 2-13, and by an average 45.08-fold and 71.50-fold in
      feces on days 7-13 (P < 0.05). Escherichia/Shigella had increased by an average
      265-fold in ileum on days 2-13, and by an average 36.70-fold in feces on days 7
      13 (P < 0.05). Acetate concentration had decreased in ileum by an average 2.88
      fold on days 2-13, and by 1.83-fold in feces on day 7 (P < 0.05). Cadaverine
      concentration had increased by an average 7.03-fold in ileum on days 2-13, and by
      an average 9.96-fold in feces on days 7-13 (P < 0.05), and fecal indole
      concentration had increased by an average 2.51-fold on days 7-13 (P < 0.05).
      Correlation analysis between significant microbes and metabolites indicated that
      the antibiotic-induced microbiota shift appeared to result in the changes of
      intestinal metabolism. In conclusion, antibiotic administration led to dynamic
      changes in microbial communities and metabolism in ileum and feces, with ileal
      microbiota being more prone to shift than fecal microbiota.

PMID- 29362825
TI  - Compost bacteria and fungi that influence growth and development of Agaricus
      bisporus and other commercial mushrooms.
AB  - Mushrooms are an important food crop for many millions of people worldwide. The
      most important edible mushroom is the button mushroom (Agaricus bisporus), an
      excellent example of sustainable food production which is cultivated on a
      selective compost produced from recycled agricultural waste products. A diverse
      population of bacteria and fungi are involved throughout the production of
      Agaricus. A range of successional taxa convert the wheat straw into compost in
      the thermophilic composting process. These initially break down readily
      accessible compounds and release ammonia, and then assimilate cellulose and
      hemicellulose into compost microbial biomass that forms the primary source of
      nutrition for the Agaricus mycelium. This key process in composting is performed
      by a microbial consortium consisting of the thermophilic fungus Mycothermus
      thermophilus (Scytalidium thermophilum) and a range of thermophilic
      proteobacteria and actinobacteria, many of which have only recently been
      identified. Certain bacterial taxa have been shown to promote elongation of the
      Agaricus hyphae, and bacterial activity is required to induce production of the
      mushroom fruiting bodies during cropping. Attempts to isolate mushroom growth
      promoting bacteria for commercial mushroom production have not yet been
      successful. Compost bacteria and fungi also cause economically important losses
      in the cropping process, causing a range of destructive diseases of mushroom
      hyphae and fruiting bodies. Recent advances in our understanding of the key
      bacteria and fungi in mushroom compost provide the potential to improve
      productivity of mushroom compost and to reduce the impact of crop disease.

PMID- 29362826
TI  - Telomere length is reduced in 9- to 16-year-old girls exposed to gestational
      diabetes in utero.
AB  - AIMS/HYPOTHESIS: Shortened telomere length is a marker of cell damage and is
      associated with oxidative stress, chronic inflammation and metabolic disease. We
      hypothesised that the offspring of women with gestational diabetes mellitus (GDM)
      with increased risk of cardiovascular and metabolic diseases might exhibit
      shorter telomere length. METHODS: We investigated telomere length in 439 GDM and
      469 control group offspring, aged between 9 and 16 years, recruited from the
      Danish National Birth Cohort. Relative telomere length was measured in peripheral
      blood DNA (n = 908) using a quantitative PCR approach. Multivariate regression
      analysis was used to investigate the association between mothers' GDM status and
      telomere length in the offspring. RESULTS: Female offspring had longer telomeres
      than males. Offspring of mothers with GDM had significantly shorter telomere
      length than control offspring, but this difference was observed only in girls.
      There was a negative association between telomere length and GDM exposure among
      the female offspring (14% shorter telomeres, p = 0.003) following adjustment for
      the age of the offspring. Telomere length in female offspring was negatively
      associated with fasting insulin levels and HOMA-IR (p = 0.03). Maternal age,
      smoking, gestational age, birthweight and the offspring's anthropometric
      characteristics were not associated with telomere length (p >= 0.1).
      CONCLUSIONS/INTERPRETATION: The 9- to 16-year-old girls of mothers with GDM had
      shorter telomeres than those from the control population. Further studies are
      needed to understand the extent to which shortened telomere length predicts
      and/or contributes to the increased risk of disease later in life among the
      offspring of women with GDM.

PMID- 29362827
TI  - Calorimetric markers for monitoring of multiple myeloma and Waldenstrom's
      macroglobulinemia patients.
AB  - The blood proteome has been studied extensively for identification of novel
      reliable disease biomarkers. In recent years, differential scanning calorimetry
      has emerged as a new tool for characterization of the thermodynamic properties of
      the major serum/plasma proteins and for the establishment of calorimetric markers
      for a variety of diseases. Here we applied calorimetry to monitor the effect of
      treatment of patients diagnosed with multiple myeloma and Waldenstrom's
      macroglobulinemia on the calorimetric profiles of patients' blood sera. The
      parameters derived from the calorimetric profiles were compared with the primary
      serum biomarkers, monoclonal immunoglobulin (M protein) concentration, and
      kappa/lambda free light chain ratio. For the secretory cases, the calorimetric
      parameters thermogram's shape similarity and weighted average center strongly
      depended on the M protein level but had lower sensitivity and specificity. By
      contrast, for non-secretory cases, the calorimetric parameters did not depend on
      the kappa/lambda free light chains ratio and exhibited significantly higher
      sensitivity and specificity than M protein levels. A combination of the
      immunological and calorimetric tests was found to greatly improve the sensitivity
      and specificity of the clinical status evaluation. The pronounced differences in
      blood sera thermograms before and during monitoring reflected the individual
      patients' response to treatment received and showed maintenance of heterogeneity
      during the disease course.

PMID- 29362828
TI  - Genetic differences in C57BL/6 mouse substrains affect kidney crystal deposition.
AB  - We previously established an experimental model of calcium oxalate crystal
      deposition in the mouse kidney using C57BL/6 mice. C57BL/6J (B6J) and C57BL/6N
      (B6N) are two core substrains of C57BL/6 mice. B6J and B6N substrains have
      approximately the same genomic sequence. However, in whole-genome analyses,
      substrains have slight genetic differences in some genes. In this study, we used
      these substrains as kidney crystal formation models and compared their genetic
      backgrounds to elucidate the pathogenic mechanisms of kidney stone formation.
      Eight-week-old male B6J and B6N mice (n = 15 in each group) were administered 80
      mg/kg glyoxylate for 12 days, and the amount of kidney crystal depositions was
      compared. The expression levels of six genes (Snap29, Fgf14, Aplp2, Lims1,
      Naaladl2, and Nnt) were investigated by quantitative polymerase chain reaction,
      and the protein levels were evaluated by western blotting and
      immunohistochemistry. The amount of kidney crystal depositions was significantly
      higher in B6J mice than in B6N mice on days 6 and 12. The expression of
      nicotinamide nucleotide transhydrogenase (Nnt) gene was significantly lower in
      B6J mice than in B6N mice. The expression of Nnt protein was observed only in B6N
      mice, and preferential high expression was seen in renal tubular epithelial
      cells. The results of this study provide compelling evidence that differences in
      mouse substrains affect kidney crystal deposition and that the absence of Nnt
      protein could be involved in crystal formation in B6J mice.

PMID- 29362829
TI  - An exploratory investigation of the effects of whole-head vibration on jaw
      movements.
AB  - The perturbing effects of vibration applied to head and body structures are known
      to destabilize motor control and elicit corrective responses. Although such
      vibration response testing may be informative for identifying sensorimotor
      deficits, the effect of whole-head vibration has not been tested on oromotor
      control. The purpose of this study was to determine how jaw movements respond to
      the perturbing effects of whole-head vibration during jaw motor tasks. Ten
      healthy adults completed speech, chewing, and two syllable repetition tasks with
      and without whole-head vibration. Jaw movements were recorded using 3D optical
      motion capture. The results showed that the direction and magnitude of the
      response were dependent on the task. The two syllable repetition tasks responded
      to vibration, although the direction of the effect differed for the two tasks.
      Specifically, during vibration, jaw movements became slower and smaller during
      the syllable repetition task that imposed speed and spatial precision demands,
      whereas jaw movements became faster and larger during the syllable repetition
      task that only imposed speed demands. In contrast, jaw movements were unaffected
      by the vibration during speech and chewing. These findings suggest that the
      response to vibration may be dependent on spatiotemporal demands, the
      availability of residual afferent information, and robust feedforward models.

PMID- 29362830
TI  - Investigating the neural basis of basic human movement perception using multi
      voxel pattern analysis.
AB  - Humans can skillfully recognize actions from others' body motion and make a
      judgment or response at once. Previous neuroimaging studies have mostly utilized
      diminished and brief human motion stimuli and indicated that human occipito
      temporal cortex plays a critical role at biological motion recognition. It
      remains unclear to what extent that the areas related to human motion perception
      are involved in decoding basic movements. Because human movement naturally stems
      from the sequences of body posture, so we utilized the stimulus of real
      movements. Participants were presented four categories of human movements (jump,
      run, skip and walk) in a blocked fMRI experiment. Multi-voxel pattern analysis
      (MVPA) was adopted to assess whether different movements could be discriminated
      in four regions. We found that movement-specific information was represented in
      both human body-sensitive areas, extrastriate body area (EBA) and motion
      sensitive areas, posterior superior temporal sulcus (pSTS) and human middle
      temporal complex (hMT+). Additionally, a further functional connectivity analysis
      using EBA as a seed was conducted and it suggested that EBA showed a task
      modulated functional connectivity with multiple areas that were involved in the
      behavior perception and motor control. Human motion processing appeared to be
      completed in a distributed network. The occipito-temporal cortex may perform the
      initial processing of human motion information extracting, and then transform
      them to interconnected areas for a further utilization.

PMID- 29362831
TI  - Various Cranial and Orbital Imaging Findings in Pediatric Abusive and Non-abusive
      Head trauma, and Relation to Outcomes.
AB  - BACKGROUND AND PURPOSE: Differentiating Abusive Head Trauma (AHT) from Non
      abusive Head trauma (NAHT) has profound clinical prognostic and legal
      implications, as certain imaging findings can individually be more suggestive of
      NAHT, while others are more suggestive of AHT. This study was set out to evaluate
      for an association between the various imaging findings in AHT with outcome.
      MATERIAL AND METHODS: Over 7-years, 55 children (age 0-4 years') with head trauma
      and magnetic resonance imaging (MRI) were included as either: abusive (n = 16),
      non-abusive (n = 35), or indeterminate (n = 4). Two pediatric neuroradiologists
      jointly reviewed the imaging. The frequency of imaging findings and their
      association with >=6 months' outcome were calculated. RESULTS: Comparing abusive
      versus non-abusive head trauma, complex subdural hematoma was present in 81% (n =
      13/16) and 29% (n = 10/35), hypoxic-ischemic injury in 44% (n = 7/16) and 6% (n =
      2/35), and diffuse axonal injury in 12% (n = 2/16) and 26% (n = 9/35),
      respectively. Susceptibility-weighted imaging (SWI) retinal hemorrhages were
      absent in non-abusive trauma (0/35), but present in 44% (n = 7/16) of the abusive
      group. In abuse, simple subdural hematomas were absent. Significant associations
      were found between the presence of abusive trauma with both hypoxic ischemic
      insult (OR = 12.83, p = 0.0024) and complex subdural hematoma (OR = 10.83, p =
      0.0007). The presence of hypoxic ischemic injury (HII) did correlate
      significantly with clinical outcome (p = 0.017), while retinal hemorrhages on SWI
      and complex subdural hematoma did not (p = 0.1696-p = 0.2496). CONCLUSION:
      Neuroimaging findings can be helpful in discriminating these two conditions on
      presentation, as well as in helping solidify the suspicion of AHT. Regarding
      eventual outcome in AHT, the most important predictor is clearly HII.

PMID- 29362833
TI  - [The Department of Urology at the Medical Center of the University of Munich and
      its partners in Central and Eastern Europe in the period from 1969 to 2004 : An
      eyewitness account].
AB  - During the 1980s, the Ludwig Maximillian University Department of Urology under
      the direction of Professor Dr. Egbert Schmiedt developed a close cooperation with
      Bulgarian urologists. As the successor of Professor Schmiedt, I have tried to
      continue this cooperation, especially in the scientific field, and also to
      integrate Romanian urology. At the request of several leading urologists of
      eastern European countries, the Central European Association of Urology which
      should act under the umbrella of European Association of Urology was founded.
      Although misunderstandings obviously prevented this, our efforts do not seem to
      have been useless-at least as far as the idea of modern European urology is
      concerned.

PMID- 29362832
TI  - Genetic mapping reveals a candidate gene (ClFS1) for fruit shape in watermelon
      (Citrullus lanatus L.).
AB  - KEY MESSAGE: A 159 bp deletion in ClFS1 gene encoding IQD protein is responsible
      for fruit shape in watermelon. Watermelon [Citrullus lanatus (Thunb.) Matsum. &
      Nakai] is known for its rich diversity in fruit size and shape. Fruit shape has
      been one of the major objectives of watermelon breeding. However, the candidate
      genes and the underlying genetic mechanism for such an important trait in
      watermelon are unknown. In this study, we identified a locus on chromosome 3 of
      watermelon genome controlling fruit shape. Segregation analysis in F2 and BC1
      populations derived from a cross between two inbred lines "Duan125" (elongate
      fruit) and "Zhengzhouzigua" (spherical fruit) suggests that fruit shape of
      watermelon is controlled by a single locus and elongate fruit (OO) is
      incompletely dominant to spherical fruit (oo) with the heterozygote (Oo) being
      oval fruit. GWAS profiles among 315 accessions identified a major locus
      designated on watermelon chromosome 3, which was confirmed by BSA-seq mapping in
      the F2 population. The candidate gene was mapped to a region 46 kb on chromosome
      3. There were only four genes present in the corresponding region in the
      reference genome. Four candidate genes were sequenced in this region, revealing
      that the CDS of Cla011257 had a 159 bp deletion which resulted in the omission of
      53 amino acids in elongate watermelon. An indel marker was derived from the 159
      bp deletion to test the F2 population and 105 watermelon accessions. The results
      showed that Cla011257 cosegregated with watermelon fruit shape. In addition, the
      Cla011257 expression was the highest at ovary formation stage. The predicted
      protein of the Cla011257 gene fitted in IQD protein family which was reported to
      have association with cell arrays and Ca2+-CaM signaling modules. Clear
      understanding of the genes facilitating the fruit shape along with marker
      association selection will be an effective way to develop new cultivars.

PMID- 29362834
TI  - [Postmenopausal lichen planopilaris also known as fibrosing frontotemporal
      alopecia Kossard : An evidence-oriented practical guide to treatment from the
      University of the Saarland, Hair Research Center of the Dr. Rolf M. Schwiete
      Foundation].
AB  - Postmenopausal lichen planopilaris (PLPP), also known as fibrosing frontotemporal
      alopecia Kossard (FFAK), is a not uncommon inflammatory scalp disease affecting
      approximately 5% of patients at specialized hair centers. The overall incidence
      of sporadic occurrence is believed to be just under 1% in the older,
      predominantly female, general population. Since the disease is often undiagnosed,
      it is statistically likely to be underrepresented. It especially occurs in
      postmenopausal women who are in the 6th and 7th decade of life (90%), but also in
      about 10% of premenopausal women, and in men it is documented only in isolated
      cases. The result is a permanent scarring hair loss accentuated at the front
      hairline with backward movement towards the neck mostly accompanied by a typical
      loss of the eyebrows. The disease therefore often leads to significant mental
      distress and social anxiety in those affected. This is the basis for a compelling
      need to develop evidence-based therapeutic concepts. While numerous retrospective
      case series have characterized the phenomenology of FFAK very well, to date there
      are no randomized controlled trials on evidence-based therapy. Here, we present
      the Homburger Evidence-Oriented Therapy Algorithm, which is oriented along the
      available case series evidence: It may (1) serve as a therapy guide for practice
      and (2) can be used as a basis for working out reliable data based on study
      evidence. The article contains detailed practical information on photo
      documentation, biopsy and histological processing up to the practical
      implementation of, for example, intralesional steroid therapy as well as
      information on selection criteria for suitable systemic therapies.

PMID- 29362835
TI  - Repeat reirradiation of the spinal cord: multi-national expert treatment
      recommendations.
AB  - BACKGROUND: Improved survival of patients with spinal bone metastases has
      resulted in an increased number of referrals for retreatment and repeat
      reirradiation. METHODS: A consortium of expert radiation oncologists (RO) has
      been established with the aim of providing treatment recommendations for
      challenging clinical scenarios for which there are no established guidelines. In
      this case, a patient developed local progression of a T5 vertebral lesion after
      two prior courses of palliative radiotherapy (time interval >12 months, assumed
      cumulative biologically equivalent dose in 2-Gy fractions [EQD2] for spinal cord
      [alpha/beta 2 Gy] 75 Gy). Expert recommendations were tabulated with the aim of
      providing guidance. RESULTS: Five of seven RO would offer a third course of
      radiotherapy, preferably with advanced techniques such as stereotactic
      radiotherapy. However, the dose-fractionation concepts were heterogeneous (3-20
      fractions) and sometimes adjusted to different options for systemic treatment.
      All five RO would compromise target volume coverage to reduce the dose to the
      spinal cord. Definition of the spinal cord planning-organ-at-risk volume was
      heterogeneous. All five RO limited the EQD2 for spinal cord. Two were willing to
      accept more than 12.5 Gy and the highest EQD2 was 19 Gy. CONCLUSIONS: The
      increasing body of literature about bone metastases and spinal cord reirradiation
      has encouraged some expert RO to offer palliative reirradiation with cumulative
      cord doses above 75 Gy EQD2; however, no consensus was achieved. Strategies for
      harmonization of clinical practice and development of evidence-based dose
      constraints are discussed.

PMID- 29362836
TI  - Urinary incontinence in nulliparous women before and during pregnancy:
      prevalence, incidence, type, and risk factors.
AB  - INTRODUCTION: While many women report urinary incontinence (UI) during pregnancy,
      associations with pre-pregnancy urinary leakage remain under-explained. METHODS:
      We performed a multi-strand prospective cohort study with 860 nulliparous women
      recruited during pregnancy. RESULTS: Prevalence of any urinary leakage was 34.8%
      before and 38.7% during pregnancy. Prevalence of UI, leaking urine at least once
      per month, was 7.2% and 17.7% respectively. Mixed urinary incontinence (MUI) was
      reported by 59.7% of women before and 58.8% during pregnancy, stress urinary
      incontinence (SUI) by 22.6% and 37.2%, and urge urinary incontinence (UUI) by
      17.7% and 4.0%, respectively. SUI accounted for half (50.0%), MUI for less than
      half (44.2%), and UUI for 5.8% of new-onset UI in pregnancy. Pre-pregnancy UI was
      significantly associated with childhood enuresis [adjusted odds ratio (AOR) 2.9,
      95% confidence interval (CI) 1.5-5.6, p = 0.001) and a body mass index (BMI) >=30
      kg/m2 (AOR 4.2, 95% CI 1.9-9.4, p <0.001). Women aged >=35 years (AOR 2.8, 95% CI
      1.4-5.9, p = 0.005), women whose pre-pregnancy BMI was 25-29.99 kg/m2 (AOR 2.0,
      95% CI 1.2-3.5, p = 0.01), and women who leaked urine less than once per month
      (AOR 2.6, 95% CI 1.6-4.1, p  <0.005) were significantly more likely to report new
      onset UI in pregnancy. CONCLUSION: Considerable proportions of nulliparous women
      leak urine before and during pregnancy, and most ignore symptoms. Healthcare
      professionals have several opportunities for promoting continence in all pregnant
      women, particularly in women with identifiable risk factors. If enquiry about UI,
      and offering advice on effective preventative and curative treatments, became
      routine in clinical practice, it is likely that some of these women could become
      or stay continent.

PMID- 29362837
TI  - Imaging in anorectal and cloacal malformations.

PMID- 29362838
TI  - Ultrasound findings in rapidly involuting congenital hemangioma (RICH) - beware
      of venous ectasia and venous lakes.
AB  - BACKGROUND: Bleeding, ulceration and cardiac failure can occur in rapidly
      involuting congenital hemangioma (RICH). Bleeding intensity ranges from
      superficial to life-threatening. OBJECTIVE: To determine whether there are
      sonographic criteria associated with an increased risk of bleeding, ulceration or
      cardiac failure in RICH in order to identify children who need close monitoring
      or prophylactic treatment. MATERIALS AND METHODS: This retrospective single
      center study included RICH patients over a period of 13 years. We evaluated
      sonographic features of RICH on B-mode and Doppler ultrasound. We correlated the
      occurrence of bleeding, ulceration and cardiac failure with four sonographic
      findings: (1) visible vessel, (2) venous ectasia, (3) venous lake and (4)
      arteriovenous shunting. RESULTS: We included 24 patients. Ulceration occurred in
      five cases, bleeding in four cases, one of which was life-threatening. Cardiac
      failure was observed more frequently in RICH with venous lakes (P=0.028).
      Bleeding and ulceration appeared more frequently in RICH with venous ectasia and
      venous lakes. Cardiac failure was associated with the presence of venous ectasia.
      All children with cardiac failure or ulceration had arteriovenous shunts.
      CONCLUSION: RICH with venous lakes on ultrasound is prone to develop bleeding,
      cardiac failure and ulceration. This association was only significant for cardiac
      failure.

PMID- 29362839
TI  - Can diffusion-weighted whole-body MRI replace contrast-enhanced CT for initial
      staging of Hodgkin lymphoma in children and adolescents?
AB  - BACKGROUND: Although positron emission tomography with 18F-fluoro-2-deoxyglucose
      (FDG-PET/CT) has been recommended as the method of choice for lymphoma staging,
      it has limited availability in several countries, therefore, studies comparing
      whole-body magnetic resonance imaging (MRI) to conventional staging methods or to
      FDG-PET/CT are an important tool to establish whole-body MRI as an alternative to
      these methods. OBJECTIVE: To compare whole-body MRI versus conventional imaging
      methods for staging of Hodgkin lymphoma in children and adolescents. MATERIALS
      AND METHODS: The study included 22 patients ages 5 to 21 years. Staging was
      performed using conventional imaging methods and whole-body MRI. Conventional
      imaging methods were defined as computed tomography (CT) of the neck, chest,
      abdomen and pelvis and ultrasonography of the neck and/or abdomen. We calculated
      the sensitivity of these methods for Hodgkin lymphoma staging and their
      sensitivity and specificity for detecting sites of nodal and extranodal
      involvement. RESULTS: The sensitivity of whole-body MRI for Hodgkin lymphoma
      staging was superior to that of conventional imaging methods (95.5% vs. 86.4%,
      respectively), but both methods had similar sensitivity and specificity for
      detecting involvement of nodal sites (99.1% and 100% vs. 97.3% and 100%,
      respectively) and extranodal sites (90.5% and 98.7% vs. 90.5% and 99.4%,
      respectively). CONCLUSION: Whole-body MRI has excellent sensitivity for staging
      of Hodgkin lymphoma in children and adolescents. It can thus be considered an
      alternative for this purpose, particularly because it does not expose patients to
      ionizing radiation.

PMID- 29362841
TI  - Spectrum of cerebral arterial and venous abnormalities in Alagille syndrome.
AB  - BACKGROUND: Alagille syndrome is a pediatric multisystem disease with increased
      prevalence of cerebrovascular disease. The spectrum of cerebrovascular disease in
      Alagille syndrome includes cerebral aneurysms, moyamoya arteriopathy and
      dolichoectasia. The prevalence of cerebrovascular disease in Alagille syndrome
      varies widely in the literature. OBJECTIVE: To determine the prevalence of
      cerebrovascular disease in our institution's Alagille patient population by
      employing a full primary review of all available neuroimaging. MATERIALS AND
      METHODS: An institutional review board-approved retrospective review of all
      Alagille syndrome patients seen at a tertiary care children's hospital from
      January 2000 to January 2014 was performed. All neuroimaging studies were
      reviewed for arterial or venous abnormalities. The prevalence of arterial and
      venous abnormalities was calculated and clinical outcomes were determined.
      RESULTS: Fifty-two patients with Alagille syndrome ranging in age from 11 months
      to 27 years were studied. Nineteen (37%) had dedicated vascular neuroimaging. Six
      (32%) had cerebral arterial disease, 4 with dolichoectasia, 3 with aneurysm(s)
      and 2 with moyamoya arteriopathy. Three of the four patients with dolichoectasia
      had associated aneurysm(s). Venous anomalies were present in 4 (21%) patients.
      One patient with moyamoya arteriopathy underwent revascularization procedures. No
      deaths were attributable to cerebrovascular disease. CONCLUSION: Cerebral
      vasculopathy is an important feature of Alagille syndrome and includes
      dolichoectasia, cerebral aneurysms and moyamoya arteriopathy. The high prevalence
      identified in our study suggests noninvasive vascular neuroimaging screening
      should be performed in this patient population. In addition to cerebral arterial
      abnormalities, alterations of venous development may be a feature of Alagille
      syndrome.

PMID- 29362840
TI  - Role of interventional radiology in managing pediatric liver tumors : Part 1:
      Endovascular interventions.
AB  - Primary liver malignancies are rare in children. Hepatoblastoma and
      hepatocellular carcinoma (HCC) together represent the overwhelming majority of
      cases. Overall survival of hepatoblastoma approaches 80% with multimodal
      treatment approaches that include chemotherapy, surgery and transplantation.
      However, there remains a subset of children with hepatoblastoma in whom resection
      or transplantation is not possible. The 5-year survival for children diagnosed
      with HCC is less than 30% and remains a significant therapeutic challenge. The
      poor outcomes for children with primary liver tumors motivate investigation of
      new therapeutic alternatives. Interventional oncology offers a broad scope of
      percutaneous and transcatheter endovascular cancer therapies that might provide
      clinical benefits. Minimally invasive approaches are distinct from medical,
      surgical and radiation oncologic treatments, and in adults these approaches have
      been established as the fourth pillar of cancer care. Transarterial
      chemoembolization is a minimally invasive locoregional treatment option performed
      by interventional radiologists with level-I evidence as standard of care in
      adults with advanced liver malignancy; transarterial chemoembolization in adults
      has served to prolong disease-free progression, downstage and bridge patients for
      surgical and transplant interventions, and improve overall survival. However,
      while several groups have reported that transarterial chemoembolization is
      feasible in children, the published experience is limited primarily to small
      retrospective case series. The lack of prospective trial evidence has in part
      limited the utilization of transarterial chemoembolization in the pediatric
      patient population. The purpose of this article is to provide an overview of the
      role of interventional radiology in the diagnosis and endovascular management of
      hepatic malignancies in children.

PMID- 29362842
TI  - CT-guided localization of pulmonary nodules in children prior to video-assisted
      thoracoscopic surgical resection utilizing a combination of two previously
      described techniques.
AB  - BACKGROUND: Pulmonary nodules in pediatric oncology patients can present a
      diagnostic and treatment dilemma. Imaging findings are often nonspecific and
      tissue diagnosis may be required for appropriate treatment. The smaller
      subpleural nodules may not be visualized and cannot be palpated during video
      assisted thoracoscopic surgical (VATS) resection. Preoperative localization has
      been beneficial in obtaining an adequate pathological specimen. OBJECTIVE: This
      study presents experience in a large pediatric hospital using CT-guided
      preoperative localization of pulmonary nodules combining two previously utilized
      techniques, hook wire and methylene blue blood patch localization. MATERIALS AND
      METHODS: A search of the electronic medical record utilizing a medical record
      search application was performed to identify all patients who underwent
      preoperative lung nodule localization during a 12.5-year period (July 1999
      through January 2012). A retrospective chart review of these patients was then
      performed. Pre- and postoperative imaging, interventional radiology procedural
      images and reports, surgical reports, and pathology reports were obtained and
      evaluated. RESULTS: Thirty-five patients, with 40 nodules, who underwent
      preoperative CT-guided lung nodule localization were identified. Patients ranged
      in age from 8 months to 21 years. The pulmonary nodules ranged in size from 1.4
      mm to 18 mm. Twelve nodules were localized using a Kopans breast lesion
      localization needle with hook wire, 4 were localized using a methylene blue blood
      patch, and 24 were localized using the combination of these two techniques. The
      technical success rate of all procedures was 100%. A pathological diagnosis was
      determined in 39 patients (97.5%). There were 6 (15.0%) minor complications and
      no major complications. CONCLUSION: CT-guided lung nodule localization using the
      combined techniques of methylene blue blood patch and hook wire is safe,
      technically feasible and successful in children. Using this combination of
      techniques will consistently yield a pathological diagnosis, is currently the
      preferred technique at our tertiary pediatric hospital and could be considered
      the new best practice.

PMID- 29362843
TI  - Mosaic-pattern dedifferentiation in liposarcoma and chondrosarcoma: imaging
      features of an uncommon form of dedifferentiation.
AB  - The term "dedifferentiation" was classically used in sarcoma pathology to refer
      to tumors in which a high-grade, undifferentiated sarcoma, or a high-grade
      sarcoma showing heterologous differentiation, arises from a pre-existing neoplasm
      of borderline or low-grade malignancy. The best recognized examples of this
      include dedifferentiated liposarcoma, arising from atypical lipomatous tumor/well
      differentiated liposarcoma, and dedifferentiated chondrosarcoma, arising from
      grade 1 hyaline chondrosarcoma of bone. In the overwhelming majority of cases,
      this dedifferentiated, high-grade sarcoma presents as a macroscopically visible
      mass, adjacent to and clearly distinct from the pre-existing low-grade lesion. It
      is less well appreciated that dedifferentiation may also occur in a so-called
      "mosaic pattern,' in which the high-grade component is intimately admixed with
      elements of the precursor lesion, forming only microscopically apparent foci.
      This mosaic or co-mingling pattern of dedifferentiation is also reflected in the
      MR imaging appearance. In contrast to the classic pattern of dedifferentiation in
      which there are two distinct juxtaposed masses with different signal intensities
      and enhancement patterns, such changes are not seen in mosaic dedifferentiation.
      The imaging features of this pattern of dedifferentiation have not been
      described. In this report we describe the imaging features of two patients with
      mosaic pattern dedifferentiation, one with liposarcoma and one with
      chondrosarcoma. In both cases the precursor lesion was correctly diagnosed by pre
      biopsy imaging, but the presence of high-grade sarcoma was not recognized.

PMID- 29362844
TI  - Prosthetic liner wear in total hip replacement: a longitudinal 13-year study with
      computed tomography.
AB  - This case report follows a woman who had a total hip replacement in 1992 when she
      was 45 years old. Six serial computed tomography (CT) examinations over a period
      of 13 years provided information that allowed her revision surgery to be limited
      to liner replacement as opposed to replacement of the entire prosthesis.
      Additionally, they provided data that ruled out the presence of osteolysis and
      indeed none was found at surgery. In 2004, when the first CT was performed, the
      3D distance the femoral head had penetrated into the cup was determined to be 2.6
      mm. By 2017, femoral head penetration had progressed to 5.0 mm. The extracted
      liner showed wear at the thinnest part to be 5.5 mm, as measured with a
      micrometer. The use of modern CT techniques can identify problems, while still
      correctable without major surgery. Furthermore, the ability of CT to assess the
      direction of wear revealed that the liner wear changed from the cranial to dorsal
      direction.

PMID- 29362845
TI  - Hypertrophic Cardiomyopathy Genotype Prediction Models in a Pediatric Population.
AB  - The Toronto Hypertrophic Cardiomyopathy (HCM) Genotype Score and Mayo HCM
      Genotype Predictor are risk assessment models developed to estimate a patient's
      likelihood of testing positive for a pathogenic variant causative of HCM. These
      models were developed from adult populations with HCM based on factors that have
      been associated with a positive genotype and have not been validated in external
      populations. The purpose of this study was to evaluate the overall predictive
      abilities of these models in a clinical pediatric HCM setting. A retrospective
      medical record review of 77 pediatric patients with gene panel testing for HCM
      between September 2005 and June 2015 was performed. Clinical and
      echocardiographic variables used in the developed models were collected and used
      to calculate scores for each patient. To evaluate model performance, the ability
      to discriminate between a carrier and non-carrier was assessed by area under the
      ROC curve (AUC) and overall calibration was evaluated by the Hosmer-Lemeshow
      goodness-of-fit statistic. Discrimination assessed by AUC was 0.72 (P < 0.001)
      for the Toronto model and 0.67 (P = 0.004) for the Mayo model. The Toronto model
      and the Mayo model showed P values of 0.36 and 0.82, respectively, for model
      calibration. Our findings suggest that these models are useful in predicting a
      positive genetic test result in a pediatric HCM setting. They may be used to aid
      healthcare providers in communicating risk and enhance patient decision-making
      regarding pursuit of genetic testing.

PMID- 29362848
TI  - Mitteilungen der DGKFO.

PMID- 29362847
TI  - Correction to: Meeting report of the 8th International Conference on "cGMP BcGMP:
      generators, effectors, and therapeutic implications" at Bamberg, Germany, from
      June 23 to 25, 2017.
AB  - The article "Meeting report of the 8 th International Conference on "cGMP BcGMP:
      generators, effectors, and therapeutic implications" at Bamberg, Germany, from
      June 23 to 25, 2017" was originally published Online First without open access.
      After publication in volume 390, issue 12, pages 1177-1188, the author decided to
      opt for Open Choice and to make the article an open access publication.

PMID- 29362846
TI  - Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and
      infection.
AB  - Pyruvate carboxylase (PC), an anaplerotic enzyme, plays an essential role in
      various cellular metabolic pathways including gluconeogenesis, de novo fatty acid
      synthesis, amino acid synthesis, and glucose-induced insulin secretion.
      Deregulation of PC expression or activity has long been known to be associated
      with metabolic syndrome in several rodent models. Accumulating data in the past
      decade clearly showed that deregulation of PC expression is associated with type
      2 diabetes in humans, while targeted inhibition of PC expression in a mouse model
      reduced adiposity and improved insulin sensitivity in diet-induced type 2
      diabetes. More recent studies also show that PC is strongly involved in
      tumorigenesis in several cancers, including breast, non-small cell lung cancer,
      glioblastoma, renal carcinoma, and gall bladder. Systems metabolomics analysis of
      these cancers identified pyruvate carboxylation as an essential metabolic hub
      that feeds carbon skeletons of downstream metabolites of oxaloacetate into the
      biosynthesis of various cellular components including membrane lipids,
      nucleotides, amino acids, and the redox control. Inhibition or down-regulation of
      PC expression in several cancers markedly impairs their growth ex vivo and in
      vivo, drawing attention to PC as an anti-cancer target. PC has also exhibited a
      moonlight function by interacting with immune surveillance that can either
      promote or block viral infection. In certain pathogenic bacteria, PC is essential
      for infection, replication, and maintenance of their virulence phenotype.

PMID- 29362851
TI  - A near-infrared fluorescent sensor with large Stokes shift for rapid and highly
      selective detection of thiophenols in water samples and living cells.
AB  - The development of simple methods with high sensitivity and selectivity to
      differentiate toxic aromatic thiols (thiophenols) from aliphatic thiols
      (cysteine, homocysteine, and glutathione) and hydrogen sulfide (H2S) is of great
      significance. Herein, we report on the fabrication of a novel near-infrared (NIR)
      fluorescent sensor for rapid and highly selective detection of thiophenols
      through the photoinduced electron transfer (PET) mechanism. In the presence of
      the thiophenols, an obvious enhancement of NIR fluorescence at 658 nm could be
      visualized with the aid of nucleophilic aromatic substitution (SNAr) reaction.
      The sensor displays large Stokes shift (~ 227 nm), fast response time (< 30 s),
      high sensitivity (~ 8.3 nM), and good biocompatibility. Moreover, the as-prepared
      sensor possesses an excellent anti-interference feature even when other possible
      interferents exist (aliphatic thiols and H2S) and has been successfully utilized
      for thiophenol detection in both water samples and living cells. Graphical
      abstract Illustration of the sensor for thiophenol imaging in living cells.

PMID- 29362849
TI  - Insights into inflammatory priming of mesenchymal stromal cells: functional
      biological impacts.
AB  - Mesenchymal stromal cells (MSCs) are multipotent adult cells with relevant
      biological properties making them interesting tools for cell-based therapy. These
      cells have the ability to home to sites of injury and secrete bioactive factors
      as part of their therapeutic functions. However, depending on the local
      environment, diverse functions of MSCs can be modulated and thus can influence
      their therapeutic value. The specific cytokine milieu within the site of
      inflammation is vital in determining the fate and cell behaviors of MSCs. Indeed,
      inflammatory signals (called as inflammatory priming), may induce critical
      changes on the phenotype, multilineage potential, hematopoietic support and
      immunomodulatory capacity of MSCs. Thus, for appropriate clinical application of
      MSCs, it is important to well know and understand these effects. In summary,
      investigating MSC interactions with the inflammatory environment is necessary to
      empower the therapeutic value of MSCs.

PMID- 29362850
TI  - Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates
      hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K+
      channels.
AB  - OBJECTIVE AND DESIGN: To investigate the role of heme oxygenase-1 (HO-1), carbon
      monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats.
      MATERIALS AND METHODS: Mechanical threshold was assessed before and 4 h after TMJ
      arthritis induction in rats. Cell influx, myeloperoxidase activity, and
      histological changes were measured in the TMJ lavages and tissues. Trigeminal
      ganglion and periarticular tissues were used for HO-1, TNF-alpha, and IL-1beta
      mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or
      1 mg kg-1), DMDC (0.025, 0.25, or 2.5 umol kg-1), biliverdin (1, 3, or 10 mg kg
      1), or ZnPP-IX (1, 3 or 9 mg kg-1) were injected (s.c.) 60 min before zymosan.
      ODQ (12.5 umol kg-1; s.c.) or glibenclamide (10 mg kg-1; i.p.) was administered 1
      h and 30 min prior to DMDC (2.5 umol kg-1; s.c), respectively. RESULTS: Hemin (1
      mg kg-1), DMDC (2.5 umol kg-1), and BVD (10 mg kg-1) reduced hypernociception and
      leukocyte migration, which ZnPP (3 mg kg-1) enhanced. The effects of DMDC were
      counteracted by ODQ and glibenclamide. The HO-1, TNF-alpha, and IL-1beta mRNA
      expression and immunolabelling increased. CONCLUSIONS: HO-1/BVD/CO pathway
      activation provides anti-nociceptive and anti-inflammatory effects on the zymosan
      induced TMJ hypernociception in rats.

PMID- 29362852
TI  - Smartphones as audience response systems for lectures and seminars.

PMID- 29362853
TI  - Volumetric absorptive microsampling as an alternative tool for therapeutic drug
      monitoring of first-generation anti-epileptic drugs.
AB  - Dosage adjustment of anti-epileptic drugs by therapeutic drug monitoring (TDM) is
      very useful, especially for the first-generation anti-epileptic drugs (AEDs).
      Microsampling-the collection of small volumes of blood-is increasingly considered
      a valuable alternative to conventional venous sampling for TDM. Volumetric
      absorptive microsampling (VAMS) allows accurate and precise collection of a fixed
      volume of blood, eliminating the volumetric blood hematocrit bias coupled to
      conventional dried blood spot collection. The aim of this study was to develop
      and validate an LC-MS/MS method for the determination and quantification of four
      anti-epileptic drugs (carbamazepine, valproic acid, phenobarbital, and phenytoin)
      and one active metabolite (carbamazepine-10,11-epoxide) in samples collected by
      VAMS. The method was fully validated based on international guidelines. Precision
      (%RSD) was below 10%, while, with a single exception, accuracy (%bias) met the
      acceptance criteria. Neither carry-over nor unacceptable interferences were
      observed, the method being able to distinguish between the isomers oxcarbazepine
      and carbamazepine-10,11-epoxide. All compounds were stable in VAMS samples for at
      least 1 month when stored at room temperature, 4  degrees C, and - 20  degrees C
      and for at least 1 week when stored at 60  degrees C. Internal standard-corrected
      matrix effects were below 10%, with %RSDs below 4%. High (> 85%) recovery values
      were obtained and the effect of the hematocrit on the recovery was overall
      limited. Successful application on external quality control materials and on left
      over patient samples demonstrated the validity and applicability of the developed
      procedure. Graphical abstract Graphical representation of the sampling, chemical
      structures, and the resulting chromatogram for volumetric absorptive
      microsampling (VAMS)-based therapeutic drug monitoring of first-generation anti
      epileptic drugs by liquid chromatography with tandem mass spectrometric
      detection.

PMID- 29362855
TI  - [Medical Knowledge in Accident Insurance : Assessing "Pneumatic Tool Damages" at
      the Bergmannsheil Hospital, 1929-1944].
AB  - The article focuses on one central element of medical activity in the context of
      the German social insurance system: providing expert assessments in accident
      pension cases. Taking an example from interwar coal mining, it aims to
      reconstruct how social policy makers first conceived of "pneumatic tool damages"
      as occupational disease and how trauma surgeons had to deal with this new entity
      of social law once it had been institutionalized in 1929. Drawing on physicians'
      publications as well as archival sources from the supreme court in social
      insurance, the Reichsversicherungsamt, the article examines how the controversial
      generation of new knowledge took place. It argues that medical knowledge was
      neither simply applied to administration and law nor was it compromised by the
      necessity to adjust it to those fields of decision-making. Expert medical
      opinions should instead be understood as a specific form of medical knowledge.

PMID- 29362854
TI  - Simultaneous quantification of endogenous and exogenous plasma glucose by isotope
      dilution LC-MS/MS with indirect MRM of the derivative tag.
AB  - Quantification of endogenous and exogenous plasma glucose can help more
      comprehensively evaluate the glucose metabolic status. A ratio-based approach
      using isotope dilution liquid chromatography tandem mass spectrometry (ID LC
      MS/MS) with indirect multiple reaction monitoring (MRM) of the derivative tag was
      developed to simultaneously quantify endo-/exogenous plasma glucose. Using
      diluted D-[13C6] glucose as tracer of exogenous glucose, 12C6/13C6 glucoses were
      first derivatized and then data were acquired in MRM mode. The metabolism of
      exogenous glucose can be tracked and the concentration ratio of endo/exo-genous
      glucose can be measured by calculating the endo-/exo-genous glucose
      concentrations from peak area ratio of specific daughter ions. Joint application
      of selective derivatization and MRM analysis not only improves the sensitivity
      but also minimizes the interference from the background of plasma, which warrants
      the accuracy and reproducibility. Good agreement between the theoretical and
      calculated concentration ratios was obtained with a linear correlation
      coefficient (R) of 0.9969 in the range of D-glucose from 0.5 to 20.0 mM, which
      covers the healthy and diabetic physiological scenarios. Satisfactory
      reproducibility was obtained by evaluation of the intra- and inter-day precisions
      with relative standard deviations (RSDs) less than 5.16%, and relative recoveries
      of 85.96 to 95.92% were obtained at low, medium, and high concentration,
      respectively. The method was successfully applied to simultaneous determination
      of the endo-/exogenous glucose concentration in plasma of non-diabetic and type
      II diabetic cynomolgus monkeys. Graphical Abstract The scheme of the proposed
      ratio-based approach using isotope dilution LC-MS/MS with indirect MRM of the
      derivative tag for simultaneous quantification of endogenous and exogenous plasma
      glucose.

PMID- 29362856
TI  - Science and Technology for Development in a Postcolonial World. Negotiations at
      the United Nations, 1960-1980.
AB  - Ever since the early 1960s, the United Nations has acknowledged science and
      technology as integral components of developmental policies. While this
      connection was initially perceived as the application of findings from scientific
      research conducted in the Global North, by the 1970s, in the context of
      negotiations for a New International Economic Order, attention shifted towards
      the structures of the global management of science. Accordingly in 1979 the UN
      Conference on Science and Technology for Development discussed possibilities of
      strengthening scientific and technological research and teaching, particularly in
      developing countries. During subsequent negotiations conflicts erupted over the
      question of how to finance programs supporting science. When the G-77 nations
      presented plans involving automatic financing schemes, these concepts proved
      incompatible with the insistence of important industrialized countries that all
      financial contributions should be voluntary. These discussions appeared to be
      concerned with the size of financial contributions. In a larger perspective,
      however, they reflected fundamentally different concepts of a world order,
      turning science and technology into a medium for far-reaching debates about
      questions of global development and justice.

PMID- 29362857
TI  - Effect of the national screening program on malignancy status of cervical cancer
      in Northern Thailand.
AB  - OBJECTIVES: Cervical cancer has posed a serious problem in Thailand for decades.
      In 2002, a systematic screening program was implemented under universal
      healthcare coverage for all Thai women. However, there has been little research
      on how screening affected particular aspects of cervical cancer, such as stage
      distribution. This screening program has a target group; therefore, it is
      necessary to assess stage and incidence trends by age of those within and outside
      the screening target group. METHODS: Using trend analysis, we assess in situ and
      malignant cervical cancers in Northern Thailand to measure changes after
      implementation of the national screening program. RESULTS: While incidence of
      malignant cancers is decreasing and incidence of in situ tumors is increasing
      across all age groups, women above age 60 still experience a high incidence of
      malignant tumors. CONCLUSIONS: The screening program is successful in the target
      group at downshifting the stage distribution of malignant tumors and reducing
      incidence of malignant tumors with in situ cases being captured. However, the
      high incidence of malignant tumors in women over age 60 will continue to be
      clinically relevant for cervical cancer management until younger generations
      undergoing screening enter this age group.

PMID- 29362858
TI  - Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an
      individual patient data multi-center meta-analysis.
AB  - INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission
      tomography (PET) provides a non-invasive method to assess cellular proliferation
      and response to antitumor therapy. Quantitative 18F-FLT uptake metrics are being
      used for evaluation of proliferative response in investigational setting, however
      multi-center repeatability needs to be established. The aim of this study was to
      determine the repeatability of 18F-FLT tumor uptake metrics by re-analyzing
      individual patient data from previously published reports using the same tumor
      segmentation method and repeatability metrics across cohorts. METHODS: A
      systematic search in PubMed, EMBASE.com and the Cochrane Library from inception
      October 2016 yielded five 18F-FLT repeatability cohorts in solid tumors. 18F-FLT
      avid lesions were delineated using a 50% isocontour adapted for local background
      on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and
      total lesion uptake (TLU) were calculated. Repeatability was assessed using the
      repeatability coefficient (RC = 1.96 * SD of test-retest differences), linear
      regression analysis, and the intra-class correlation coefficient (ICC). The
      impact of different lesion selection criteria was also evaluated. RESULTS: Images
      from four cohorts containing 30 patients with 52 lesions were obtained and
      analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma,
      and 33 in non-small cell lung cancer patients). A good correlation was found
      between test-retest data for all 18F-FLT uptake metrics (R2 >= 0.93; ICC >=
      0.96). Best repeatability was found for SUVpeak (RC: 23.1%), without significant
      differences in RC between different SUV metrics. Repeatability of proliferative
      volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection
      methods based on SUVmax >= 4.0 improved the repeatability of volumetric metrics
      (RC: 26-28%), but did not affect the repeatability of SUV metrics. CONCLUSIONS:
      In multi-center studies, differences >= 25% in 18F-FLT SUV metrics likely
      represent a true change in tumor uptake. Larger differences are required for FLT
      metrics comprising volume estimates when no lesion selection criteria are
      applied.

PMID- 29362859
TI  - 68Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer.
AB  - PURPOSE: The aims of this retrospective analysis were to compare 68Ga-PSMA PET
      findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative
      and quantitative 68Ga-PSMA PET data in patients with prostate cancer (PC) bone
      metastases. METHODS: In total, 152 PET/CT scans from 140 patients were evaluated.
      Of these patients, 30 had previously untreated primary PC, and 110 had
      biochemical relapse after treatment of primary PC. All patients underwent dynamic
      PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with
      68Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually),
      semiquantitatively (SUV), and quantitatively based on a two-tissue compartment
      model and a noncompartmental approach leading to the extraction of the fractal
      dimension. Differences were considered significant for p values <0.05. RESULTS:
      In total, 168 68Ga-PSMA-positive and 113 CT-positive skeletal lesions were
      detected in 37 patients (8 with primary PC, 29 with biochemical recurrence). Of
      these 168 lesions, 103 were both 68Ga-PSMA PET-positive and CT-positive, 65 were
      only 68Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that
      there were significantly more 68Ga-PSMA PET-positive lesions than CT-positive
      lesions. Association analysis showed that PSA plasma levels were significantly
      correlated with several 68Ga-PSMA-11-associated parameters in bone metastases,
      including the degree of tracer uptake (SUVaverage and SUVmax), its transport rate
      from plasma to the interstitial/intracellular compartment (K1), its rate of
      binding to the PSMA receptor and its internalization (k3), its influx rate (Ki),
      and its distribution heterogeneity. CONCLUSION: 68Ga-PSMA PET/CT is a useful
      diagnostic tool in the detection of bone metastases in PC. 68Ga-PSMA PET
      visualizes more bone metastases than low-dose CT. PSA plasma levels are
      significantly correlated with several 68Ga-PSMA PET parameters.

PMID- 29362860
TI  - Regional histologic differences in the long head of the biceps tendon following
      subpectoral biceps tenodesis in patients with rotator cuff tears and SLAP
      lesions.
AB  - PURPOSE: The purpose of this study was to quantify the regional histology of the
      long head of the biceps tendon (LHBT) and compare the histopathology present to
      clinical findings in patients with rotator cuff tears and SLAP lesions. METHODS:
      Prospectively enrolled patients undergoing an open subpectoral LHBT tenodesis in
      the setting of a rotator cuff (RTC) tear or SLAP lesion. Perioperative data were
      collected and the excised LHBT was analyzed by a fellowship trained pathologist.
      Tendons were sectioned into proximal (biceps anchor), middle (bicipital groove),
      and distal (myotendinous junction) portions. Sections were stained with Movat's
      pentachrome stain and digitized for analysis. Comparisons were made between the
      histologic findings present in the setting of a rotator cuff tear with those seen
      in the setting of a SLAP tear. RESULTS: 39 tendons were analyzed: 20 from
      patients with SLAP lesions (mean age of 44.7 years, range 23-60 years) and 19
      from patients with rotator cuff tears (mean age of 58.7 years, range 43-71).
      Patients with the most pathologic tendons in the bicipital groove were
      significantly older (59.4 vs. 50.4 years; p < 0.05), reported higher pre
      operative VAS scores (6.6 vs. 5.0; p < 0.02), and demonstrated lower pre
      operative ASES scores (41.6 vs. 50.7; p < 0.05). The RTC group showed
      significantly more mucinous degeneration at both the proximal (p < 0.03) and the
      middle (p < 0.01) tendon portions compared to the SLAP group. In both groups, the
      portions of proximal tendon showed significantly (p < 0.05) more mucinous
      degeneration than distal portions. CONCLUSION: Regional histologic differences
      exist in the LHBT. Rotator cuff patients showed the most degenerated tendon in
      the bicipital groove and these patients tended to be older and have higher VAS
      and lower ASES scores. Surgeons should consider performing a subpectoral biceps
      tenodesis as the bicipital groove portion of the tendon may be very degenerated,
      especially in patients with rotator cuff disease. Additional research is
      warranted to distinguish whether treating the biceps differently in distinct
      geographic regions affects patient outcomes. LEVEL OF EVIDENCE: II.

PMID- 29362862
TI  - The development of an in vitro Pig-a assay in L5178Y cells.
AB  - A recent flow cytometry-based in vivo mutagenicity assay involves the hemizygous
      phosphatidylinositol class A (Pig-a) gene. Pig-a forms the catalytic subunit of N
      acetylglucosaminyltransferase required for glycophosphatidylinositol (GPI) anchor
      biosynthesis. Mutations in Pig-a prevent GPI-anchor synthesis resulting in loss
      of cell-surface GPI-linked proteins. The aim of the current study was to develop
      and validate an in vitro Pig-a assay in L5178Y mouse lymphoma cells. Ethyl
      methanesulfonate (EMS)-treated cells (186.24-558.72 ug/ml; 24 h) were used for
      method development and antibodies against GPI-linked CD90.2 and stably expressed
      CD45 were used to determine GPI-status by flow cytometry. Antibody concentration
      and incubation times were optimised (0.18 ug/ml, 30 min, 4  degrees C) and Zombie
      VioletTM (viability marker; 0.5%, 30 min, RT) was included. The optimum
      phenotypic expression period was 8 days. The low background mutation frequency of
      GPI-deficiency [GPI(-)] in L5178Y cells (0.1%) constitutes a rare event, thus
      flow cytometry acquisition parameters were optimised; 104 cells were measured at
      medium flow rate to ensure a CV <= 30%. Spiking known numbers of GPI(-) cells
      into a wild-type population gave high correlation between measured and spiked
      numbers (R2 0.999). We applied the in vitro Pig-a assay to a selection of well
      validated genotoxic and non-genotoxic compounds. EMS, N-ethyl-N-nitrosourea and 4
      nitroquinoline-N-oxide dose dependently increased numbers of GPI(-) cells, while
      etoposide, mitomycin C, and a bacterial-specific mutagen did not. Cycloheximide
      and sodium chloride were negative. Sanger sequencing revealed Pig-a mutations in
      the GPI(-) clones. In conclusion, this in vitro Pig-a assay could complement the
      in vivo version, and follow up weak Ames positives and late-stage human
      metabolites or impurities.

PMID- 29362861
TI  - Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP
      in human estrogen receptor-positive mammary cells: mechanistic support for
      lifestyle factors (cooked red meat and ethanol) associated with mammary cancer.
AB  - Consumption of cooked/processed meat and ethanol are lifestyle risk factors in
      the aetiology of breast cancer. Cooking meat generates heterocyclic amines such
      as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Epidemiology,
      mechanistic and animal studies indicate that PhIP is a mammary carcinogen that
      could be causally linked to breast cancer incidence; PhIP is DNA damaging,
      mutagenic and oestrogenic. PhIP toxicity involves cytochrome P450 (CYP1 family)
      mediated metabolic activation to DNA-damaging species, and transcriptional
      responses through Aryl hydrocarbon receptor (AhR) and estrogen-receptor-alpha (ER
      alpha). Ethanol consumption is a modifiable lifestyle factor strongly associated
      with breast cancer risk. Ethanol toxicity involves alcohol dehydrogenase
      metabolism to reactive acetaldehyde, and is also a substrate for CYP2E1, which
      when uncoupled generates reactive oxygen species (ROS) and DNA damage. Here,
      using human mammary cells that differ in estrogen-receptor status, we explore
      genotoxicity of PhIP and ethanol and mechanisms behind this toxicity. Treatment
      with PhIP (10-7-10-4 M) significantly induced genotoxicity (micronuclei
      formation) preferentially in ER-alpha positive human mammary cell lines (MCF-7,
      ER-alpha+) compared to MDA-MB-231 (ER-alpha-) cells. PhIP-induced CYP1A2 in both
      cell lines but CYP1B1 was selectively induced in ER-alpha(+) cells. ER-alpha
      inhibition in MCF-7 cells attenuated PhIP-mediated micronuclei formation and
      CYP1B1 induction. PhIP-induced CYP2E1 and ROS via ER-alpha-STAT-3 pathway, but
      only in ER-alpha (+) MCF-7 cells. Importantly, simultaneous treatments of
      physiological concentrations ethanol (10-3-10-1 M) with PhIP (10-7-10-4 M)
      increased oxidative stress and genotoxicity in MCF-7 cells, compared to the
      individual chemicals. Collectively, these data offer a mechanistic basis for the
      increased risk of breast cancer associated with dietary cooked meat and ethanol
      lifestyle choices.

PMID- 29362863
TI  - Innovative organotypic in vitro models for safety assessment: aligning with
      regulatory requirements and understanding models of the heart, skin, and liver as
      paradigms.
AB  - The development of improved, innovative models for the detection of toxicity of
      drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new
      products safely to market in a cost-effective and timely manner. In addition,
      improvement in models to detect toxicity may reduce the incidence of unexpected
      post-marketing toxicity and reduce or eliminate the need for animal testing. The
      safety of novel products of the pharmaceutical, chemical, or cosmetics industry
      must be assured; therefore, toxicological properties need to be assessed.
      Accepted methods for gathering the information required by law for approval of
      substances are often animal methods. To reduce, refine, and replace animal
      testing, innovative organotypic in vitro models have emerged. Such models appear
      at different levels of complexity ranging from simpler, self-organized three
      dimensional (3D) cell cultures up to more advanced scaffold-based co-cultures
      consisting of multiple cell types. This review provides an overview of recent
      developments in the field of toxicity testing with in vitro models for three
      major organ types: heart, skin, and liver. This review also examines regulatory
      aspects of such models in Europe and the UK, and summarizes best practices to
      facilitate the acceptance and appropriate use of advanced in vitro models.

PMID- 29362865
TI  - [Medical education in motion].

PMID- 29362864
TI  - Tacrolimus-induced nephrotoxicity in mice is associated with microRNA
      deregulation.
AB  - Although Tacrolimus is an immunosuppressive drug widely used in renal
      transplantation, its chronic use paradoxically induces nephrotoxic effects, in
      particular renal fibrosis, which is responsible for chronic allograft dysfunction
      and represents a major prognostic factor of allograft survival. As molecular
      pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are
      poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic
      effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1 mg/kg/d
      for 28 days) resulted in kidney injury and was associated with alteration of a
      gene expression signature associated with cellular stress, fibrosis and
      inflammation. Tacrolimus also affected renal miRNA expression, including miRNAs
      previously involved in fibrotic and inflammatory processes as "fibromirs" such as
      miR-21-5p, miR-199a-5p and miR-214-3p. In agreement with in vivo data, Renal
      Proximal Tubular Epithelial cells exposed to Tacrolimus (25 and 50 uM) showed
      upregulation of miR-21-5p and the concomitant induction of epithelial phenotypic
      changes, inflammation and oxidative stress. In conclusion, this study suggests
      for the first time that miRNAs, especially fibromiRs, participate to Tacrolimus
      induced nephrotoxic effects. Therefore, targeting miRNAs may be a new therapeutic
      option to counteract Tacrolimus deleterious effects on kidney.

PMID- 29362866
TI  - [Kit-based radiolabeling of PSMA ligands].

PMID- 29362867
TI  - The stem cell factor-stimulated melanogenesis in human melanocytes can be
      abrogated by interrupting the phosphorylation of MSK1: evidence for involvement
      of the p38/MSK1/CREB/MITF axis.
AB  - We recently found that treatment of normal human melanocytes (NHMs) with the
      antioxidant astaxanthin (AX) suppresses the stem cell factor (SCF)-stimulated
      protein expression levels of microphthalmia-associated transcription factor
      (MITF) at 1.5 h and of tyrosinase and endothelin B receptor at 96 h post
      treatment. Analysis of the signaling cascade(s) involved revealed that although
      the major SCF-activated signaling cascade that leads to CREB activation (the c
      KIT/Shc/Raf-1/ERK/RSK/CREB axis) is not interrupted, the increased
      phosphorylation of CREB is significantly abrogated by AX. We show for the first
      time that treatment of NHMs with SCF activates the p38/mitogen and stress
      activated kinase (MSK1) axis in a c-KIT dependent fashion. Interestingly, whereas
      AX does not abrogate the SCF-induced activation of p38, it does affect the
      increased phosphorylation of its downstream target, MSK1. The lineage connection
      of p38/MSK1 activation with CREB activation and its associated MITF expression is
      supported by our finding that while silencing MSK1 abolishes the activation of
      CREB and the subsequent increase in total MITF proteins at 15 min and at 1.5 h,
      respectively, post-stimulation with SCF, inhibitors of p38 and of MSK1 abrogate
      the SCF-induced increase in total MITF proteins at 1.5 h post-stimulation. These
      findings suggest that SCF-stimulated melanogenesis can be abrogated by
      interrupting MSK1 phosphorylation, providing evidence for involvement of the
      p38/MSK1/CREB/MITF axis, providing new evidence for the ROS depletion independent
      interruption by antioxidants of SCF-triggered signaling.

PMID- 29362868
TI  - Effect of topical timolol on response rate and adverse events in infantile
      hemangioma: a meta-analysis.
AB  - A number of clinical trials evaluated the effect of topical timolol in the
      treatment of infantile hemangioma and provided inconsistent results. The present
      study assessed the response rate and adverse events of topical timolol in the
      treatment of infantile hemangioma. Pubmed, Embase, China National Knowledge
      Infrastructure (CNKI), Wanfang, and Cochrane library were searched until October
      2016. Specific inclusion criteria were used to evaluate articles. Risk ratios
      (RRs) with 95% confidence intervals (CIs) were calculated. The meta-analysis was
      performed using a random effect model. A total of 10 studies, comprising 887
      infants with hemangioma, were included. The response rate was reported in eight
      trials; these studies compared the topical timolol to laser, observation,
      placebo, or propranolol. The heterogeneity was statistically significant (P <
      0.00001, I2 = 83%). The difference in the response rate was significant (RR =
      2.86, 95% CI 1.31-6.24) while comparing the topical timolol to the controls.
      However, no significant difference in the response rate was observed while
      comparing the topical timolol to propranolol (RR = 0.99, 95% CI 0.70-1.42). The
      difference in the adverse events was found to be significant (RR = 0.21, 95% CI
      0.05-0.97) when the timolol group was compared to the control group. This meta
      analysis confirmed that the topical timolol alone was more beneficial on response
      rate and adverse event than laser, placebo, and observation. The response rate
      did not differ significantly when comparing the topical timolol to propranolol.
      However, further studies are essential using an improved design of the study.

PMID- 29362869
TI  - Antiplatelet and anticoagulant agents in vitreoretinal surgery: a prospective
      multicenter study involving 804 patients.
AB  - PURPOSE: To assess the rate of hemorrhagic complications after vitreoretinal
      surgery and the influence of antithrombotic agents. METHODS: Hemorrhagic
      complications of vitreoretinal procedures performed in seven ophthalmologic
      centers on patients treated or not treated with antiplatelet (AP) or
      anticoagulant (AC) agents were prospectively collected. Patients'
      characteristics, surgical techniques, and complications were recorded during
      surgery and for 1 month after. RESULTS: Eight hundred four procedures were
      performed between January 2015 and April 2015. Among them, 18.4% were treated
      with AP agents (n = 148) and 7.8% with AC agents (n = 63), with 18 of them
      treated with NOACS (new oral anticoagulants). AP or AC agents were continued in
      96.5% and 80.7% of cases, respectively. Fifty-three patients (6.6%) developed one
      or more hemorrhagic complications in one eye during this period. In univariate
      analysis, AC agents were not associated with hemorrhagic complications (P =
      0.329) in contrast to AP (P = 0.005). However, in multivariate analysis, AP
      agents were no longer associated with hemorrhagic complications and the
      intraoperative use of endodiathermy was the only factor associated with
      hemorrhagic complications (P = 0.001). CONCLUSIONS: This study showed that AP and
      AC agents were not a factor associated with hemorrhagic complications during
      vitreoretinal surgery. The continuation of these treatments should be considered
      without risk of severe hemorrhagic complications.

PMID- 29362870
TI  - Ligictaluridus michaelalicea n. sp. (Monogenea: Dactylogyridae) from flathead
      catfish (Pylodictis olivaris) in the upper Mississippi River, including remarks
      on taxonomy influencing monogenean treatment regulation in the United States.
AB  - Ligictaluridus michaelalicea n. sp. (Monogenea: Dactylogyridae, Ancyrocephalinae)
      is described from the gills of Pylodictis olivaris (Siluriformes: Ictaluridae)
      from Wisconsin and Iowa portions of the upper Mississippi River. Diagnostic
      features include a relatively large, strongly curved tubular cirrus with minor
      terminal flare; an accessory piece with a prominent basal lobe and a simple,
      thick terminal limb featuring a thin lateral flange and blunt distal tip devoid
      of recurved hooks. The sinistral vagina, two prostatic reservoirs, and a terminal
      seminal vesicle of the vas deferens are prominent. The anchors, ventral and
      dorsal bars, and hooks are similar in overall form to those of other members of
      the genus. The description includes sequence data for the 18S rRNA gene, which
      aligned most closely with species of ancyrocephaline monogeneans, with the
      highest similarity being with Ligictaluridus pricei (Mueller, 1936). Other
      monogenean species identified from the flathead catfish examined included L.
      pricei and Ligictaluridus mirabilis (Mueller, 1937). L. michaelalicea n. sp. is
      the fourth species to be described from P. olivaris within its natural range in
      central and eastern North America. Implications resulting from taxonomic name
      changes, including species of Ligictaluridus, and United States Food and Drug
      Administration treatment regulations are discussed. An updated key to species of
      the genus Ligictaluridus is presented.

PMID- 29362871
TI  - Assessment of turkey vehicle container microclimate on transit during summer
      season conditions.
AB  - This study evaluated the formed microclimate commercial truck transport practices
      effects on the turkeys' welfare by measuring Dead on Arrival (DOA) index and
      pale, soft, and exudative (PSE-like) meat occurrence. The experimental design was
      entirely randomized in a 6 * 2 factorial arrangements (two truck container
      compartments * six water shower groups) with birds positioned at superior front
      (SF), inferior front (IF), superior middle (SM), inferior middle (IM), superior
      rear (SR), and inferior rear (IR) and two bath treatments: with water shower
      (WiS) and without water shower (WoS) with eight replications for each treatment.
      The animals were transported for 95 min' journey from the farm to the
      slaughterhouse under hot-humidity conditions. The results shown herein indicated
      the formation of a thermal core at the inferior middle and rear truck container
      regions, because the heat produced by the birds and the influence of developed
      microclimate consisting of temperature, relative humidity, and air ventilation.
      The IM and IR container compartments under the WoS treatment presented the
      highest (P < 0.01) numbers of PSE-like meat incidence and DOA index values
      compared with those located at the front under WiS treatment as the consequence
      of the altered to birds unbearable conditions within the container microclimate
      in transit. The formed microclimate during the commercial transport practices
      under hot-humidity conditions affected the bird's welfare consequently turkey
      meat qualities.

PMID- 29362872
TI  - Zornia latifolia: a smart drug being adulterated by Stylosanthes guianensis.
AB  - Dried herbal preparations, based on "Zornia latifolia," are commonly sold on web,
      mainly for their supposed hallucinogenic properties. In this work, we demonstrate
      that these commercial products contain a different Fabacea, i.e., Stylosanthes
      guianensis, a cheaper plant, widely cultivated in tropical regions as a fodder
      legume. We were provided with plant samples of true Zornia latifolia from Brazil,
      and carried out a thorough comparison of the two species. The assignment of
      commercial samples was performed by means of micro-morphological analysis, DNA
      barcoding, and partial phytochemical investigation. We observed that Z. latifolia
      contains large amounts of flavonoid di-glycosides derived from luteolin,
      apigenin, and genistein, while in S. guianensis lesser amounts of flavonoids,
      mainly derived from quercetin, were found. It is likely that the spasmolytic and
      anxiolytic properties of Z. latifolia, as reported in traditional medicine,
      derive from its contents in apigenin and/or genistein.

PMID- 29362874
TI  - Complex signatures of natural selection at GYPA.
AB  - The human MN blood group antigens are isoforms of glycophorin A (GPA) encoded by
      the gene, GYPA, and are the most abundant erythrocyte sialoglycoproteins. The
      distribution of MN antigens has been widely studied in human populations yet the
      evolutionary and/or demographic factors affecting population variation remain
      elusive. While the primary function of GPA is yet to be discovered, it serves as
      the major binding site for the 175-kD erythrocyte-binding antigen (EB-175) of the
      malarial parasite, Plasmodium falciparum, a major selective pressure in recent
      human history. More specifically, exon two of GYPA encodes the receptor-binding
      ligand to which P. falciparum binds. Accordingly, there has been keen interest in
      understanding what impact, if any, natural selection has had on the distribution
      of variation in GYPA and exon two in particular. To this end, we resequenced GYPA
      in individuals sampled from both P. falciparum endemic (sub-Saharan Africa and
      South India) and non-endemic (Europe and East Asia) regions of the world.
      Observed patterns of variation suggest that GYPA has been subject to balancing
      selection in populations living in malaria endemic areas and in Europeans, but no
      such evidence was found in samples from East Asia, Oceania, and the Americas.
      These results are consistent with malaria acting as a selective pressure on GYPA,
      but also suggest that another selective force has resulted in a similar pattern
      of variation in Europeans. Accordingly, GYPA has perhaps a more complex
      evolutionary history, wherein on a global scale, spatially varying selective
      pressures have governed its natural history.

PMID- 29362875
TI  - Impact of updating the non-radiation parameters in the ICRP 103 detriment model.
AB  - The radiation detriment in ICRP 103 is defined as the product of the organ
      specific risk coefficient and the damage that may be associated with a cancer
      type or hereditary effect. This is used to indicate a weighted risk according to
      the radiation sensitivity of different organs and the severity of damage that may
      possibly arise. While the risk refers to radiation exposure parameters, the
      extent of damage is independent of radiation. The parameters that are not
      affected by radiation are lethality, impairment of quality of life, and reduced
      life expectancy, which are considered as quantities associated with the severity
      of disease or damage. The damage and thus the detriment appear to be mostly
      affected by lethality, which is the quotient of the age-standardized mortality
      rate to the incidence rate. The analysis of the detriment presented in this paper
      focuses on the influence of the lethality on the detriment from 1980 to 2012 in
      the USA and Germany. While the lethality in this period covering more than three
      decades has decreased approximately linearly by 30% (both USA and Germany),
      within the same period the detriment declined only by 13% in the USA and by 15%
      in Germany. If only based on these two countries, an update on the detriment
      parameters with reference to 2007, when ICRP 103 was released, would result in a
      reduced weighted risk, i.e. the radiation detriment would be reduced by 10 to 15%
      from originally 5.7% per Sv for the whole population to roughly 5% per Sv.

PMID- 29362873
TI  - Molecular tissue changes in early myocardial ischemia: from pathophysiology to
      the identification of new diagnostic markers.
AB  - Diagnosing early myocardial ischemia (the initial 4 to 6 h after interruption of
      blood flow to part of the myocardium) remains a challenge for clinical and
      forensic pathologists. Several immunohistochemical markers have been proposed for
      improving postmortem detection of early myocardial ischemia; however, no single
      marker appears to be both sufficiently specific as well as sensitive. This review
      summarizes the diverse categories of molecular tissue markers that have been
      investigated in human autopsy samples with acute myocardial infarction as well as
      in the well-established and widely used in vivo animal model of early myocardial
      ischemia (permanent ligation of the coronary artery). Recently identified markers
      appearing during the initial 2 h of myocardial ischemia are highlighted. Among
      them, only six were tested for specificity (C5b-9, hypoxia-inducible factor 1
      alpha, vascular endothelial growth factor, heart fatty acid binding protein,
      connexin 43, and JunB). Despite the discovery of several potentially promising
      markers (in terms of early expression and specificity), many of them remain to be
      tested and validated for application in routine diagnostics in clinical and
      forensic pathology. In particular, research investigating the postmortem
      stability of these markers is required before any might be implemented into
      routine diagnostics. Establishing a standardized panel of immunohistochemical
      markers may be more useful for improving sensitivity and specificity than
      searching for a single marker.

PMID- 29362876
TI  - Variability of Denosumab densitometric response in postmenopausal osteoporosis.
AB  - The objective of our prospective study is to specify the variability of
      densitometric response to Denosumab, given in the second line, and to try to
      understand the reasons. All menopausal patients with primary osteoporosis,
      treated by Denosumab in our centre from 2014 to 2015, were included in this open
      prospective work. At T0, the patient's age, type of fracture, and previous
      treatments were collated. At T0 and T1, after 1 year of treatment by Dmab, a DXA
      of the spine and the hip and a determination of CTX were performed. Sixty-three
      patients aged 68.8 +/- 8.3 years were included. The median number of treatments
      prescribed for osteoporosis before switch to Denosumab was 2.4. The median
      duration of these treatments was 7.2 years. At T1, CTX was less than 33 pg/ml
      (minimum threshold for our assay kit) in all patients. The median BMD in the
      spine increased by + 5.44% compared to T0. 14 patients in the upper quartile had
      a median BMD gain in the spine of + 11.07%. Fourteen patients in the lower
      quartile had a median BMD gain in the spine of + 0.6%. Only the duration of
      previous treatments, which was greater in the non-responder group, differed
      between these two groups. In the total cohort, the spinal densitometric gain was
      negatively correlated with the age of the patient at baseline (p = 0.04), the
      duration of previous treatment (p = 0.02), and positively with the CTX level (p =
      0.05). The Dmab densitometric response is highly variable, partly explained by
      the duration of previous treatments and the level of bone resorption at
      initiation of treatment.

PMID- 29362877
TI  - Science and fashion: inflammation and oxidative stress in psychiatry.

PMID- 29362878
TI  - [Influence of computer-based cognitive training on mobility in healthy older
      adults : A systematic review].
AB  - BACKGROUND: Mobility is important and often affected in older adults. Mobility is
      related to cognitive function, which is associated with age-related decline.
      Computer-based cognitive training (CCT) is increasingly used to treat such
      cognitive deficits. Whether CCT also has an effect on mobility is not yet clear.
      OBJECTIVE: The aim of this systematic review was to identify and evaluate
      available intervention studies investigating the effect of CCT on mobility
      related outcome parameters in healthy older adults. METHODS: Studies with CCT
      interventions with mobility outcome parameters (gait, balance, transfer) as
      primary outcomes and published up to June 2017 were categorized based on the
      criteria of the American Academy for Cerebral Palsy and Developmental Medicine
      (AACPDM) and then systematically evaluated. RESULTS: Out of 305 identified
      studies, 11 CCT studies met the inclusion criteria. The quality of these studies
      was generally high but definitions and effects of mobility outcome parameters
      were heterogeneous. The most promising mobility outcome parameters that may be
      influenced by CCT are step length under dual tasking conditions and gait
      initiation. CONCLUSION: The use of CCT may have positive effects on mobility
      parameters. Further studies focusing on this hypothesis as the primary outcome
      parameter are needed.

PMID- 29362879
TI  - Infection Function of Adhesin-Like Protein ALP609 from Spiroplasma melliferum CH
      1.
AB  - Spiroplasma melliferum is the causative agent of spiroplasmosis in honeybees.
      During infection, adhesion of spiroplasmas to the host cells through adhesion
      factors is a crucial step. In this study, we identified an adhesin-like protein
      (ALP609) in S. melliferum CH-1 and investigated its role in the infection. To
      determine whether ALP609 is an adhesion factor, we performed indirect
      immunofluorescence microscopy to visualize its adhesion properties. Subsequently,
      an infection model of S. melliferum CH-1 was established using primary midgut
      cells of Apis mellifera to examine the adhesion and invasion of spiroplasma using
      anti-ALP609 antibodies inhibition assays and competition assays with recombinant
      ALP609 in vitro. We found that anti-ALP609 antibodies could inhibit the adhesion
      and invasion of spiroplasma to the midgut cells of A. mellifera and reduce midgut
      cell invasion on increased exposure to recombinant ALP609. To the best of our
      knowledge, this is the first report identifying adhesion-related factors in S.
      melliferum. Our results suggested that ALP609 is an adhesin-like protein critical
      for invasion of S. melliferum CH-1 into midgut cells of A. mellifera.

PMID- 29362880
TI  - Spirosoma agri sp. nov., Isolated from Apple Orchard Soil.
AB  - A Gram-negative, non-motile, rod-shaped, aerobic bacterial strain, designated S7
      3-3T, was isolated from apple orchard soil in Gyeongsangnam-do province, South
      Korea, and was characterized taxonomically using a polyphasic approach.
      Phylogenetic analysis based on 16S rRNA gene sequence showed that strain S7-3-3T
      belonged to the family Cytophagaceae in the phylum Bacteroidetes was most closely
      related to Spirosoma rigui WPCB118T (94.3%), Spirosoma pulveris JSH5-14T (93.9%),
      and Spirosoma linguale DSM 74T (93.7%). The strain showed typical chemotaxonomic
      characteristics of the genus Spirosoma with a predominant respiratory quinone of
      menaquinone MK-7 and the major fatty acids of summed feature 3 (C16:1
      omega7c/C16:1 omega6c; 43.9%) and C16:1 omega5c (25.6%). The G+C content of
      genomic DNA was 49.6 mol%. The polar lipid profile contained major amounts of
      phosphatidylethanolamine, an unidentified aminophospholipid, and an unidentified
      polar lipid. Phenotypic and chemotaxonomic data supported the affiliation of
      strain S7-3-3T with the genus Spirosoma. The results of physiological and
      biochemical tests showed the genotypic and phenotypic differentiation of the
      isolate from recognized Spirosoma species. On the basis of its phenotypic
      properties, genotypic distinctiveness, and chemotaxonomic features, strain S7-3
      3T represents a novel species of the genus Spirosoma, for which the name
      Spirosoma agri sp. nov. is proposed. The type strain is S7-3-3T (= KCTC 52727T =
      JCM 32199T).

PMID- 29362881
TI  - Outcome of concomitant resection of the replaced right hepatic artery in
      pancreaticoduodenectomy without reconstruction.
AB  - PURPOSE: It has been reported that preoperative embolization or intraoperative
      reconstruction of the replaced right hepatic artery (rRHA) in order to secure the
      arterial blood flow to the liver and biliary tract are useful for patients who
      have undergone pancreaticoduodenectomy (PD) with concomitant rRHA resection. In
      this study, the feasibility of concomitant resection of rRHA in PD without
      preoperative embolization or intraoperative reconstruction were retrospectively
      evaluated with a particular focus on postoperative complications. METHODS: We
      retrospectively analyzed 323 consecutive patients who underwent PD. RESULTS: In
      51 patients (15.8%), an rRHA was detected. Nine of 51 patients underwent combined
      rRHA resection during PD. Eight patients showed tumor abutment, and one patient
      had accidental intraoperative damage of the rRHA. Although there were no cases of
      bilioenteric anastomotic failure, a hepatic abscess occurred in one patient. This
      patient was treated with percutaneous transhepatic abscess drainage and was cured
      immediately without suffering sepsis. Postoperative complications of Clavien
      Dindo classification >= IIIa were found in three patients, and R0 resection was
      achieved in six. Surgical outcomes showed no significant differences between the
      rRHA-resected and non-resected groups. Moreover, there were no significant
      differences in laboratory data related to liver functions between the rRHA
      resected and non-resected groups before surgery and on postoperative days 1, 3,
      5, and 7. CONCLUSIONS: Simple resection of the rRHA following an unintended or
      accidental injury during PD is not associated with severe morbidity and should be
      considered as an alternative to a technically difficult reconstruction.

PMID- 29362882
TI  - Extended pancreatectomy as defined by the ISGPS: useful in selected cases of
      pancreatic cancer but invaluable in other complex pancreatic tumors.
AB  - PURPOSE: Extended pancreatectomy aimed at R0 resection of pancreatic tumors with
      adjacent vessel and organ involvement may be the only option for cure. This study
      was done with an objective to analyze the short- and long-term outcomes of
      extended pancreatic resections. METHODS: All pancreatectomies performed between
      2006 and 2015 were included. The pancreatectomies were classified as standard or
      extended, as per the International Study Group for Pancreatic Surgery. All
      surgical complications and terminologies were according to Clavien-Dindo
      classification and International Study Group for Pancreatic Surgery guidelines.
      Morbidity and mortality were primary outcomes and disease-free survival was a
      secondary outcome. RESULTS: Sixty-three extended and 620 standard
      pancreatectomies were performed. Major morbidity (Clavien grades III, IV and V)
      (37 vs. 29%, p = 0.21) and mortality (6 vs. 4%, p = 0.3) for extended
      pancreatectomies were comparable to those for standard pancreatectomies. Blood
      loss > 855 ml, need for blood transfusion, and tumor size were independent risk
      factors for morbidity, and the latter two for mortality. Standard
      pancreatectomies were associated with better 3-year disease-free survival than
      extended pancreatectomies (67 vs. 41%, p < 0.001). Extended pancreatectomies
      resulted in a significantly better median disease-free survival for non
      pancreatic adenocarcinoma vs. pancreatic adenocarcinoma (33.3 vs. 9.5 months, p =
      0.01). CONCLUSION: Extended pancreatectomies resulted in similar peri-operative
      morbidity and mortality compared to standard pancreatectomies. Although the
      survival of patients undergoing these complex procedures is inferior to standard
      pancreatectomies, they should be undertaken not only in selected cases of
      pancreatic cancer but even more so in other complex pancreatic tumors.

PMID- 29362883
TI  - Bidirectional association between weight status and motor skills in adolescents :
      A 4-year longitudinal study.
AB  - BACKGROUND: Despite considerable efforts the prevalence of overweight and obesity
      in youth remains high. Poor motor skills have been associated with increased body
      weight but there is still limited information on the longitudinal association of
      these health parameters. AIM: This study examined the prospective association
      between motor skills and body weight in 10- to 14-year-old youth. METHODS: Body
      weight, height and motor skills, assessed via the German motor test 16-18
      (Deutscher Motorik Test, DMT6-18), were measured in 213 middle school students
      (57% male) every year over a 4-year period. Club sports participation and
      migration status were assessed via a questionnaire. RESULTS: Besides an inverse
      cross-sectional association between body weight and motor skills, excess body
      weight was associated with impaired development of motor skills (p < 0.05).
      Furthermore, weight loss was associated with enhanced motor development and
      allowed previously overweight students to catch up with their normal weight
      peers. High motor skills at baseline also reduced the odds of becoming
      overweight/obese during the observation period. These results were independent of
      club sports participation. CONCLUSION: There is a bidirectional, synergistic
      association between body weight and motor skills. Facilitating the development of
      motor skills in children and adolescents may therefore be a viable intervention
      strategy targeting weight management and physical activity in youth.

PMID- 29362884
TI  - Complications of CT-guided transthoracic lung biopsy : A short report on current
      literature and a case of systemic air embolism.
AB  - Percutaneous computed tomography (CT)-guided transthoracic needle biopsy (PCNB)
      is a common diagnostic procedure and is especially indispensable in thoracic
      oncology. Complications, such as pulmonary hemorrhage and pneumothorax are
      frequent, but usually easy to manage. Systemic air embolism is a rare but
      relevant adverse event and its true incidence is probably underestimated, as not
      all cases may become clinically apparent. We present a case of systemic air
      embolism following a core-needle biopsy of a left upper lobe lesion, where
      immediately after the procedure CT scans documented air in the thoracic aorta and
      in the left ventricle. In this context, we review the current literature on
      technical aspects as well as on frequent and infrequent major complications of
      PCNB, together with risk factors, emergency treatment and prevention strategies.

PMID- 29362885
TI  - Two invasive herbivores on a shared host: patterns and consequences of
      phytohormone induction.
AB  - Herbivore-induced changes in host quality mediate indirect interactions between
      herbivores. The nature of these indirect interactions can vary depending on the
      identity of herbivores involved, species-specific induction of defense-signaling
      pathways, and sequence of attack. However, our understanding of the role of these
      signaling pathways in the success of multiple exotic herbivores is less known.
      Eastern hemlock (Tsuga canadensis) is attacked by two invasive herbivores
      [elongate hemlock scale (EHS; Fiorinia externa) and hemlock woolly adelgid (HWA;
      Adelges tsugae)] throughout much of its range, but prior attack by EHS is known
      to deter HWA. The potential role of phytohormones in this interaction is poorly
      understood. We measured endogenous levels of phytohormones in eastern hemlock in
      response to attack by these invasive herbivores. We also used exogenous
      application of methyl jasmonate (MJ) and acibenzolar-S-methyl (ASM), a salicylic
      acid (SA) pathway elicitor, to test the hypothesis that defense-signaling
      phytohormones typically induced by herbivores could deter HWA. Resistance to
      adelgid attack was assessed using a behavioral assay. Adelgid feeding
      significantly elevated both abscisic acid (ABA) and SA in local tissues, while
      EHS feeding had no detectable effect on either phytohormone. HWA progrediens and
      sistens crawlers preferred to settle on ASM-treated foliage. In contrast, HWA
      crawlers actively avoided settlement on MJ-treated foliage. We suggest that
      induction of ABA- and SA-signaling pathways, in concert with defense-signaling
      interference, may aid HWA invasion success, and that defense-signaling
      interference, induced by exotic competitors, may mediate resistance of native
      hosts.

PMID- 29362886
TI  - Pheochromocytoma and paraganglioma: genotype versus anatomic location as
      determinants of tumor phenotype.
AB  - To date, germline or somatic genetic events can be detected for at least 60% of
      paragangliomas. Strong genotype-phenotype associations have been recognized and
      become increasingly refined. Characteristics closely linked with genotype include
      syndromic presentation, age of onset, risk of metastatic disease and predominant
      anatomic site. In contrast, profiles of catecholamine secretion appear to be
      largely determined by anatomic location or cell type of origin. This review
      summarizes current knowledge of genotype-phenotype correlations for
      paragangliomas in different locations and scrutinizes previous publications on
      the respective tissues of origin to find potential explanations for site-related
      differences. We hypothesize that differential sensitivities of distinct
      chromaffin cell populations to hypoxia are major determinants of these
      differences, with increased sensitivity to hypoxia likely exacerbating
      vulnerability to mutation-derived disruption of hypoxic signaling pathways.
      Potential involvement of endothelin-1, tumor necrosis factor type 1 receptor
      associated protein and the hypoxia-inducible miR-210 in the development of
      abdomino-thoracic or head and neck paragangliomas are discussed. Recognition of
      factors that predispose to chromosomal losses, or amplify sub-threshold molecular
      alterations towards tumorigenic events in different (chromaffin) cell types, may
      facilitate the leap from developing targeted therapies towards establishment of
      tumor preventative measures.

PMID- 29362887
TI  - Rumination impairs the control of stimulus-induced retrieval of irrelevant
      information, but not attention, control, or response selection in general.
AB  - The aim of the study was to throw more light on the relationship between
      rumination and cognitive-control processes. Seventy-eight adults were assessed
      with respect to rumination tendencies by means of the LEIDS-r before performing a
      Stroop task, an event-file task assessing the automatic retrieval of irrelevant
      information, an attentional set-shifting task, and the Attentional Network Task,
      which provided scores for alerting, orienting, and executive control functioning.
      The size of the Stroop effect and irrelevant retrieval in the event-five task
      were positively correlated with the tendency to ruminate, while all other scores
      did not correlate with any rumination scale. Controlling for depressive
      tendencies eliminated the Stroop-related finding (an observation that may account
      for previous failures to replicate), but not the event-file finding. Taken
      altogether, our results suggest that rumination does not affect attention,
      executive control, or response selection in general, but rather selectively
      impairs the control of stimulus-induced retrieval of irrelevant information.

PMID- 29362888
TI  - The roles of consistency and exclusivity in perceiving body ownership and agency.
AB  - Previous rubber/virtual hand illusion studies have established important
      constraints for the illusion that an artificial effector becomes part of one's
      own body (perceived ownership), and that its actions are being caused by oneself
      (perceived agency). We can take these observed constraints to establish two of
      three Wegner's (Trends Cogn Sci 7:65-69; Wegner, Trends in Cognitive Sciences
      7:65-69, 2003) criteria for the perception of personal agency: priority and
      consistency, but not Wegner's third criterion-exclusivity. In this study we
      tested with virtual hand illusion, whether exclusivity (participant is certain
      who was controlling the virtual effector) can also be established. We manipulated
      two factors: exclusivity and consistency. Our results show that on both ownership
      and agency judgments, consistency and exclusivity produced main effects, and the
      two effects interacted in an underadditive fashion. Taken together, these
      findings provide support for our suggestion to extend Wegner's agency theory to
      explain perceived body ownership, which in turn provides an integrative framework
      for interpreting constraints on ownership and agency illusions.

PMID- 29362890
TI  - Yonsei Experience of 5000 Gasless Transaxillary Robotic Thyroidectomies: Reply.

PMID- 29362889
TI  - Computer-driven quantitative image analysis in the assessment of tumor cell and T
      cell features in diffuse large B cell lymphomas.
AB  - Diffuse large B cell lymphoma (DLBCL) is recognized as the most common non
      Hodgkin lymphoma subtype. Advanced high-resolution digital scans of pathology
      slides have enabled the development of computer-based image analysis algorithms
      that may assist pathologists in quantifying immunohistochemical stains. In this
      retrospective study, we reviewed data from 29 patients affected by DLBCL. In
      order to evaluate the number of tumor cells and microenvironment T cells, we
      performed an analysis of CD20, Ki67, and CD3 counts, assessed with the Positive
      Pixel Count algorithm embedded in the Aperio ImageScope software. A lower tumor
      cell count was observed in patients with a non-germinal center immunophenotype,
      high LDH, splenomegaly and an IPI >= 3. A lower number of CD3 was observed in
      patients with bulky disease, an IPI >= 3 and disease stage 3-4. Overall, these
      data confirm that quantitative analysis of the tumor cells and of the tumor
      microenvironment by means of computer-driven quantitative image analysis may add
      new information in DLBCL diagnosis.

PMID- 29362891
TI  - Post-operative Complications Following Emergency Operations Performed by Trainee
      Surgeons: A Retrospective Analysis of Surgical Deaths.
AB  - BACKGROUND: Adequate surgical care of patients and concurrent training of
      residents is achieved in elective procedures through careful case selection and
      adequate supervision. Whether this applies when trainees are involved in
      emergency operations remains equivocal. The aim of this study was therefore to
      compare the risk of post-operative complications following emergency procedures
      performed by senior operators compared with supervised trainees. METHODS: This is
      a retrospective cohort study examining in-hospital deaths of patients across all
      surgical specialties who underwent emergency surgery in Australian public
      hospitals reported to the national surgical mortality audit between 2009 and
      2015. Multivariable logistic regression was used to explore whether there was an
      association between the level of operator experience (senior operator vs trainee)
      and the occurrence of post-operative surgical complications following an
      emergency procedure. RESULTS: Our population consisted of 6920 patients. There
      were notable differences between the trainees and senior operator groups;
      trainees more often operated on patients aged over 80 years, with cardiovascular
      and neurological risk factors. Senior operators more often operated on very young
      and obese patients with advanced malignancy and hepatic disease. Supervised
      trainees had a lower rate of post-operative complications compared with senior
      operators; 18% (n = 396) and 25% (n = 1210), respectively (p < 0.05). Operations
      performed by trainees were associated with an 18% decrease (95% CI 5-29%; p <
      0.05) in odds of post-operative complications compared with senior operators,
      adjusting for potential confounders. CONCLUSIONS: Contrary to popular belief, our
      results suggest that supervised trainees safely perform emergency operations,
      provided that cases are judiciously selected.

PMID- 29362892
TI  - Comparison of Adverse Events and Outcomes Between Patients With and Without Drain
      Insertion After Hepatectomy: A Propensity Score-Matched, Multicenter, Prospective
      Observational Cohort Study in Japan (CSGO-HBP-001).
AB  - BACKGROUND: Adverse events (AEs) after hepatectomy (Hx) have decreased. The aim
      of this study was to assess the safety of Hx and to identify the risks and
      benefits of drain insertion. METHODS: From 2010 to 2012, a multicenter,
      prospective cohort study was conducted in consecutive patients who underwent Hx.
      Patients who were scheduled to undergo Hx with neither reconstruction of the
      biliary tract nor concomitant resection of other organs were excluded. AEs were
      graded based on the Clavien-Dindo classification. Univariate analysis was
      performed to identify the risks and benefits in all cases and in selected cases
      matched by propensity score. RESULTS: This study included 197 patients. AEs
      occurred in 20 (10.1%). In all cases, no difference in the rate of AE was
      observed between those with and without drain insertion. Postoperative hospital
      stay in the group with drains (n = 132) was statistically longer than that in the
      group without drains (n = 65) (17.7 vs. 11.5 days, P = 0.001). In patients
      without AE (n = 177), hospital stay in the group with drains was statistically
      longer than that in the group without drains (14.1 vs. 11.3 days, P < 0.001). In
      propensity score-matched cases (41 cases in each group), postoperative hospital
      stay in the group with drains was also statistically longer than that in the
      group without drains (17.3 vs. 11.4 days, P = 0.003). CONCLUSION: Drain insertion
      after hepatectomy may lead to longer hospital stay in patients with and without
      AE.

PMID- 29362893
TI  - Adaptive Management of Environmental Flows.
AB  - Adaptive management enables managers to work with complexity and uncertainty, and
      to respond to changing biophysical and social conditions. Amid considerable
      uncertainty over the benefits of environmental flows, governments are embracing
      adaptive management as a means to inform decision making. This Special Issue of
      Environmental Management presents examples of adaptive management of
      environmental flows and addresses claims that there are few examples of its
      successful implementation. It arose from a session at the 11th International
      Symposium on Ecohydraulics held in Australia, and is consequently dominated by
      papers from Australia. We classified the papers according to the involvement of
      researchers, managers and the local community in adaptive management. Five papers
      report on approaches developed by researchers, and one paper on a community-led
      program; these case studies currently have little impact on decision making. Six
      papers provide examples involving water managers and researchers, and two papers
      provide examples involving water managers and the local community. There are no
      papers where researchers, managers and local communities all contribute equally
      to adaptive management. Successful adaptive management of environmental flows
      occurs more often than is perceived. The final paper explores why successes are
      rarely reported, suggesting a lack of emphasis on reflection on management
      practices. One major challenge is to increase the documentation of successful
      adaptive management, so that benefits of learning extend beyond the project where
      it takes place. Finally, moving towards greater involvement of all stakeholders
      is critical if we are to realize the benefits of adaptive management for
      improving outcomes from environmental flows.

PMID- 29362894
TI  - The ontogeny of the 300 million year old xiphosuran Euproops danae
      (Euchelicerata) and implications for resolving the Euproops species complex.
AB  - Xiphosurans have often been considered as archaic appearing cheliceratan
      arthropods, with a rich fossil record. We describe here parts of the post
      embryonic ontogeny of the 300 million year old xiphosuran Euproops danae
      (Xiphosura sensu stricto, Euchelicerata), from the Mazon Creek Lagerstatte (Upper
      Carboniferous), USA. Recently, the ontogeny of a closely related species,
      Euproops sp. from the Upper Carboniferous Piesberg quarry, Osnabruck, Germany
      (informally called 'Piesproops'), has been reconstructed. This analysis has drawn
      characters into question that were used to differentiate E. danae from another
      species occurring at the same time, Euproops rotundatus from the British Middle
      Coal Measures. More precisely, early post-embryonic stages of Piesproops resemble
      E. danae; later stages resemble E. rotundatus. Based on this earlier study, the
      here-described reinvestigation of E. danae has been performed as the ontogenetic
      sequence itself may yield more reliable characters for differentiating species of
      Euproops. We could identify eight different growth stages for E. danae. This
      ontogenetic sequence shows a comparable growth to that of Piesproops, but differs
      markedly in the development of the opisthosomal flange. This character may serve
      as a basis for reliably differentiating these species. Additionally, analysing
      the ontogeny of further species may offer the basis for identifying heterochronic
      shifts in the evolution of xiphosurans.

PMID- 29362895
TI  - In vivo live imaging of bone cells.
AB  - There are as many as 200 cell types in the body, and highly sophisticated and
      varied life phenomena are carried out by cell migration to appropriate places at
      appropriate times following the appropriate interactions. Recent advances in
      optical imaging technology using multi-photon excitation microscopy have enabled
      visualization inside intact bone tissues in living animals without thin
      sectioning. Using such advanced techniques, the dynamic behaviors of living bone
      cells on intact bone tissue structures can be elucidated. Here, we focus on
      recent findings using intravital multi-photon imaging of dynamic biological
      systems, e.g., bone homeostasis. This novel approach has proven beneficial for
      understanding the mechanisms underlying the spatiotemporal nature of bone
      remodeling systems and for evaluating the specific modes of actions of novel
      drugs currently in development, which will contribute to a new chapter in bone
      and mineral research.

PMID- 29362896
TI  - Comparison of retropubic, laparoscopic and robotic radical prostatectomy: who is
      the winner?
AB  - PURPOSE: This study is a systematic analysis of the evidence regarding
      oncological, perioperative and postoperative outcomes and the cost of open
      retropubic radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP)
      and robotic-assisted laparoscopic radical prostatectomy (RALP). METHODS: Summary
      data was abstracted from 104 original research articles representing 227,400
      patients. PubMed/Medline, Scopus, Google Scholar, EMBASE and the Cochrane Library
      were reviewed in December 2016. A total of 104 publications were selected for
      inclusion. The primary outcomes were positive surgical margin (PSM) and major
      complication rate according to Clavien classifications. Secondary outcomes were
      operative time, length of hospital stay, estimated blood loss, transfusions,
      conversions, rate of post-operative erectile dysfunction and incontinence and
      total cost of procedure. RESULTS: ORP had a significantly higher rate than RALP
      for PSM (OR: 1.18; 95% CI 1.05-1.32; p = 0.004), but the rate of PSM was not
      significantly different between ORP versus LRP (OR: 1.37; 95% CI 0.88-2.14; p =
      0.17) and RALP versus LRP (OR: 0.83; 95% CI 0.40-1.72; p = 0.62). The major
      Clavien complication rate was significantly different between ORP and RALP (OR:
      2.14; 95% CI 1.24-3.68; p = 0.006). Estimated blood loss, transfusions and length
      of hospital stay were low for RALP, moderate for LRP and high for ORP. The rate
      of erectile dysfunction (OR: 2.58; 95% CI 1.77-3.75; p < 0.001) and incontinence
      (OR: 3.57; 95% CI 2.28-5.58; p < 0.001) were significantly lower after RALP than
      LRP and equivalent for other comparisons. Total cost was highest for RALP,
      followed by LRP and ORP. CONCLUSIONS: For PSM and peri- and post-operative
      complications, RALP showed better results than ORP and LRP. In the context of the
      biases between the studies, one should interpret the results with caution.

PMID- 29362897
TI  - Early double J stent removal in renal transplant patients to prevent urinary
      tract infection - systematic review and meta-analysis of randomized controlled
      trials.
AB  - Ureteral stents are routinely used in renal transplant and are associated with
      reduced urological complications but increased urinary tract infections (UTIs).
      There is no agreement on the preferred time to removal of stents after
      transplantation. We performed a systematic review and meta-analysis of all
      randomized controlled trials (RCTs) comparing stent duration of <14 days vs > =14
      days. Electronic databases were searched to identify RCTs that compared early vs
      late stent removal. Primary outcome was urinary tract infections. Secondary
      outcomes included various urological complications. No significant difference in
      UTI rates was demonstrated between short and long stent duration (relative risk
      (RR) 0.85, 95% confidence interval (CI) 0.44-1.64), with significant
      heterogeneity (I2 = 86%). Sensitivity analysis evaluating studies with low risk
      of bias for allocation concealment demonstrated statistically significant lower
      rates of UTI with short stent duration (RR 0.48, 95% CI 0.32-0.71) with no
      heterogeneity. No significant difference was demonstrated for the outcome of
      major urological complications (RR 0.72, 95% CI 0.50-1.05), without
      heterogeneity. Ureteral stenosis rates were significantly lower in the short
      duration arm (RR 0.42, 95% CI 0.18-0.98). Early removal of ureteral stents after
      renal transplant may be associated with reduced rates of UTI and ureteral
      stenosis. Additional RCTs are needed.

PMID- 29362898
TI  - Androgen Therapy for Acute Myeloid and Hairy Cell Leukemia.
AB  - OPINION STATEMENT: The purpose of this paper is to review the preclinical and
      clinical rationale for androgen therapy of acute myeloid (AML) and hairy cell
      leukemia (HCL). A major recent positive study should renew interest in this
      therapy, which has been reported to be effective in these leukemias for more than
      50 years. Hopefully, renewed interest in this approach, which seems promising,
      will lead to well-designed modern studies that will precisely define a role for
      androgens in these leukemias. A recent large prospective, randomized study has
      demonstrated enhanced survival for elderly AML patients who present with WBC
      counts < 30,000/MUL have improved overall survival when androgens are given post
      remission, and numerous case reports suggest that androgens frequently restore
      normal peripheral blood counts in severely pancytopenic patients with HCL. Well
      designed prospective studies are needed to precisely define which patients are
      most likely to benefit from androgen therapy and where in the treatment plan they
      should be incorporated.

PMID- 29362899
TI  - Costs of dose escalation among ulcerative colitis patients treated with
      adalimumab in Germany.
AB  - AIMS: We determined adalimumab utilisation and associated drug costs in patients
      with ulcerative colitis (UC), focusing on patients requiring dose escalation.
      METHODS: The retrospective cohort study analysed the de-identified prescription
      data of the Arvato Health Analytics (Munich, Germany) database (2010-2015) in
      adult UC patients undergoing adalimumab therapy. RESULTS: A total of 154 patients
      were newly treated with adalimumab (average 39.6 years, 53% females), with a mean
      dose of 2.93 mg/day. Within 12 months, 69 patients (45%) received a dose increase
      of > 50% (doubled dose in 48 patients; 32%), with the escalation reported at
      169.3 +/- 99.3 days. A subsequent dose de-escalation to the standard dose
      occurred in 50 (32%) of patients that initially had a dose increase of > 50%
      (after 94.7 +/- 49.6 days). Direct drug costs were 28,846 ? in the overall study
      population, 24,934 ? in patients on standard dose, 36,094 ? in patients with dose
      increase, and 32,742 ? in patients with increase and subsequent decrease.
      CONCLUSION: Dose escalation occurred frequently, and in one third of patients the
      dose was at least doubled. Dose escalations were associated with substantial
      increases in direct drug costs. Dose escalation of adalimumab can severely affect
      both the health care system and the drug budget of the physician. It needs to be
      considered that other biologic medications may constitute a more cost-effective
      alternative.

PMID- 29362900
TI  - The effect of online gambling on gambling problems and resulting economic health
      costs in Germany.
AB  - Problematic and pathological gambling have emerged as substantial problems in
      many countries. One potential accelerating factor for this phenomenon during
      recent years is the Internet, which offers different kinds of games and online
      applications for gambling that are faster, more attractive due to a variety of
      design and marketing options, less costly and potentially more addictive than
      terrestrial gambling opportunities. However, the contributing role of the
      Internet for problematic gambling has not been analyzed sufficiently so far and
      remains inconclusive. The current study is based on a representative sample with
      15,023 individuals from Germany. With a new concept of assessing online gambling
      with its relative fraction of total gambling activities and a control-function
      approach to account for possible endogeneity of online gambling, we estimate the
      impact of online gambling on gambling behavior while additionally controlling for
      a rich set of important covariates, like education, employment situation and
      family status. The results show that, on average, replacing 10% of offline
      gambling with online gambling increases the likelihood of being a problematic
      gambler by 8.8-12.6%. This increase is equivalent to 139,322 problematic gamblers
      and 27.24 million ? per year of additional expenditures in the German health
      sector. Our findings underpin the necessity to keep online gambling restricted to
      prevent further developments of problematic and pathological gambling in Germany.

PMID- 29362901
TI  - Reconstructing an incomparable organism: the Chalicothere in nineteenth and early
      twentieth century palaeontology.
AB  - Palaeontology developed as a field dependent upon comparison. Not only did
      reconstructing the fragmentary records of fossil organisms and placing them
      within taxonomic systems and evolutionary lineages require detailed anatomical
      comparisons with living and fossil animals, but the field also required thinking
      in terms of behavioural, biological and ecological analogies with modern
      organisms to understand how prehistoric animals lived and behaved. Yet
      palaeontological material often worked against making easy linkages, bringing a
      sense of mystery and doubt. This paper will look at an animal whose study
      exemplified these problems: the Chalicothere. Increasingly (although not
      unproblematically) recognized as a specific type from finds across North America
      and Eurasia from the early nineteenth century onwards, these prehistoric mammals
      showed short back legs terminating in pawed feet, long front limbs ending in
      sharp claws, a long flexible neck, and herbivorous grinding teeth. The
      Chalicothere became a significant organism within palaeontological studies, as
      the unexpected mix of characters made it a textbook example against the Cuvierian
      notion of "correlation of parts," while explaining how the animal moved, fed and
      behaved became puzzling. However, rather than prevent comparisons, these actually
      led to comparative analogies becoming flexible and varied, with different forms
      of comparison being made with varying methods and degrees of confidence, and with
      the anatomy, movement and behaviour of giraffes, bears, horses, anteaters,
      primates and other organisms all serving at various points as potential models
      for different aspects of the animal. This paper will examine some of the attempts
      to reconstruct and define the Chalicotheres across a long timescale, using this
      to show how multiple comparisons and analogies could be deployed in a
      reconstructive and evolutionary science like palaeontology, and illustrate some
      of the limits and tensions in comparative methods, as they were used to
      reconstruct organisms which were thought to be incomparable to any modern animal.

PMID- 29362902
TI  - A phase I dose escalation trial of nab-paclitaxel and fixed dose radiation in
      patients with unresectable or borderline resectable pancreatic cancer.
AB  - PURPOSE: Patients with locally advanced pancreatic cancer typically have poor
      outcomes, with a median survival of approximately 16 months. Novel methods to
      improve outcomes are needed. Nab-paclitaxel (Abraxane) has shown efficacy in
      pancreatic cancer and is FDA-approved for metastatic disease in combination with
      gemcitabine. Nab-paclitaxel is also a promising radiosensitizer based on
      laboratory studies, but it has never been clinically tested with definitive
      radiotherapy for locally advanced pancreatic carcinoma. METHODS: We performed a
      phase 1 study using a 3 + 3 dose escalation strategy to determine the safety and
      tolerability of dose-escalated nab-paclitaxel with fractionated radiotherapy for
      patients with unresectable or borderline resectable pancreatic cancer. Following
      induction chemotherapy with two cycles of nab-paclitaxel and gemcitabine,
      patients were treated with weekly nab-paclitaxel and daily radiotherapy to a dose
      of 52.5 Gy in 25 fractions. Final dose-limiting toxicity (DLT) determination was
      performed at day 65 after the start of radiotherapy. RESULTS: Nine patients
      received nab-paclitaxel at a dose level of either 100 mg/m2 (n = 3) or 125 mg/m2
      (n = 6). There were no observed grade 3 gastrointestinal toxicities. One DLT
      (grade 3 neuropathy) was observed in a patient who received 125 mg/m2 of nab
      paclitaxel. Other grade 3 toxicities included fatigue (11%), anemia (11%) and
      neutropenia (11%). No grade 4 toxicities were observed. Following
      chemoradiotherapy, four patients (borderline resectable, n = 2 and unresectable,
      n = 2) underwent surgical resection, all with negative margins and with
      significant treatment effect with limited tumor viability. CONCLUSIONS: The
      combination of fractionated radiation and weekly full dose nab-paclitaxel was
      safe and well-tolerated.

PMID- 29362903
TI  - Comparative assessment of pharmacokinetics, and pharmacodynamics between
      RTXM83TM, a rituximab biosimilar, and rituximab in diffuse large B-cell lymphoma
      patients: a population PK model approach.
AB  - PURPOSE: The main objective was to quantify any potential differences in
      pharmacokinetic (PK) parameters (AUC and Cmax) between RTXM83, a proposed
      rituximab biosimilar, and its reference product, using a population PK model
      approach. METHODS: Rituximab PK and PD data were obtained from a randomized,
      double-blind, phase III clinical study (RTXM83-AC-01-11) in patients with diffuse
      large B-cell lymphoma (DLBCL) that received 375 mg/m2 intravenous RTXM83 or its
      reference product with CHOP regimen, every 3 weeks, for six cycles. Rituximab
      levels were quantified by Meso Scale Discovery assay. PK analysis was performed
      using NONMEM 7.3.0. The effect of disease and patient covariates on RXTM83 PK was
      investigated. Model was evaluated using visual predictive check and non
      parametric bootstrap. RESULTS: In total, 251 DLBCL patients (127 and 124 in
      RXTM83-CHOP and rituximab-CHOP arms, respectively) and 5341 serum concentrations
      (2703 for RXTM83 and 2638 for rituximab, respectively) were available for the
      population PK analysis. The volume of distribution of the central compartment
      (V1) and clearance of RXTM83 were estimated at 3.19 L and 12.5 mL/h,
      respectively. Body surface area allowed to explain the interindividual
      variability for V1. A statistical analysis showed that systemic exposure (AUC and
      Cmax) of RTXM83 was similar to rituximab. The 90% confidence intervals for all
      pairwise comparisons were within the predefined bioequivalence interval of 0.80
      1.25. PD similarity of B-cell depletion and recovery was also observed.
      CONCLUSIONS: The time course of RTXM83 was well characterized by the model
      developed. The systemic exposure of RTXM83 and its associated variability were
      similar to those for rituximab reference in DLBCL patients, demonstrating PK
      similarity. The PD similarity of RTXM83 and rituximab reference product was also
      demonstrated.

PMID- 29362904
TI  - Atrial Fibrillation Ablation and its Impact on Stroke.
AB  - Atrial fibrillation (AF) is a commonly encountered arrhythmia, which is not yet
      fully understood. Catheter ablation has shown to be an effective strategy for
      rhythm management and several small or retrospective studies have shown that
      stroke rates are decreased in ablated AF patients compared to those medically
      managed. Several studies even show that ablation returns stroke risk to that of
      non-AF patients. Large scale, prospective trials will further illuminate this
      connection and provide mechanistic understanding of the role of the procedure
      versus the process of selection for the procedure and peri- and post-procedural
      therapy and management. Furthermore, modification of risk factors associated with
      AF show a significant increase in the sustained success of AF ablation and can
      also moderate the progression of AF.

PMID- 29362905
TI  - Role of Chemotherapy in the Neoadjuvant/Adjuvant Setting for Patients With Rectal
      Adenocarcinoma Undergoing Chemoradiotherapy and Surgery or Radiotherapy and
      Surgery.
AB  - Rectal cancer has been successfully managed in the last couple of decades. In the
      USA, as the initial approach, neoadjuvant concurrent chemoradiation has been
      associated not only with decrease in tumor size and recurrence but also with
      higher resection rate with minimal side effects. Data support that addition of
      chemotherapy to radiotherapy is superior to radiotherapy alone in the neoadjuvant
      setting. Recent debates have addressed the question of administration of adjuvant
      chemotherapy following surgery. In this article, we discuss the role of
      chemotherapy in both the neoadjuvant and the adjuvant settings for locally
      advanced rectal cancer.

PMID- 29362906
TI  - Experience in colon sparing surgery in North America: advanced endoscopic
      approaches for complex colorectal lesions.
AB  - BACKGROUND: Need for colon sparing interventions for premalignant lesions not
      amenable to conventional endoscopic excision has stimulated interest in advanced
      endoscopic approaches. The aim of this study was to report a single institution's
      experience with these techniques. METHODS: A retrospective review was conducted
      of a prospectively collected database of all patients referred between 2011 and
      2015 for colorectal resection of benign appearing deemed endoscopically
      unresectable by conventional endoscopic techniques. Patients were counseled for
      endoscopic submucosal dissection (ESD) with possible combined endoscopic
      laparoscopic surgery (CELS) or alternatively colorectal resection if unable to
      resect endoscopically or suspicion for cancer. Lesion characteristic, resection
      rate, complications, and outcomes were evaluated. RESULTS: 110 patients were
      analyzed [mean age 64 years, female gender 55 (50%), median body mass index 29.4
      kg/m2]. Indications for interventions were large polyp median endoscopic size 3
      cm (range 1.5-6.5) and/or difficult location [cecum (34.9%), ascending colon
      (22.7%), transverse colon (14.5%), hepatic flexure (11.8%), descending colon
      (6.3%), sigmoid colon (3.6%), rectum (3.6%), and splenic flexure (2.6%)]. Lesion
      morphology was sessile (N = 98, 93%) and pedunculated (N = 12, 7%). Successful
      endoscopic resection rate was 88.2% (N = 97): ESD in 69 patients and CELS in 28
      patients. Complication rate was 11.8% (13/110) [delayed bleeding (N = 4),
      perforation (N = 3), organ-space surgical site infection (SSI) (N = 2),
      superficial SSI (N = 1), and postoperative ileus (N = 3)]. Out of 110 patients,
      13 patients (11.8%) required colectomy for technical failure (7 patients) or
      carcinoma (6 patients). During a median follow-up of 16 months (range 6-41
      months), 2 patients had adenoma recurrence. CONCLUSIONS: Advanced endoscopic
      surgery appears to be a safe and effective alternative to colectomy for patients
      with complex premalignant lesions deemed unresectable with conventional
      endoscopic techniques.

PMID- 29362907
TI  - Prospective randomized study comparing single-incision laparoscopic versus multi
      trocar laparoscopic totally extraperitoneal (TEP) inguinal hernia repair at 2
      years.
AB  - BACKGROUND: Inguinal hernia repair via multi-trocar laparoscopy (MTL) has gained
      an increasing popularity worldwide. Single-incision laparoscopy (SIL) has been
      introduced to reduce the port-related complications and to improve the cosmetic
      results. The authors report a prospective randomized study comparing SIL versus
      MTL totally extraperitoneal (TEP) inguinal hernia repair. METHODS: Between
      January 2013 and May 2015, 113 versus 97 patients were prospectively randomized
      between SILTEP and MTLTEP. Perioperative, short-term, and mid-term outcomes have
      been assessed. The primary endpoint was the mid-term outcomes (late postoperative
      complications, late inguinal hernia recurrence, surgical and cosmetic
      satisfactions). Secondary endpoints were perioperative outcomes (operative time,
      mesh fixation, operative complications, postoperative pain, and hospital stay)
      and short-term outcomes (early postoperative complications, early inguinal hernia
      recurrence, and days to return to normal activities). RESULTS: After a mean
      follow-up of 27 +/- 8 months, a statistically significant difference was found
      between the two groups in terms of mean operative time for both unilateral and
      bilateral inguinal hernia repair (p = 0.016; p = 0.039) and cosmetic satisfaction
      (p = 0.003). CONCLUSION: Perioperative, short-term, and mid-term outcomes were
      comparable between the two groups. At 2-year follow-up, a significant shorter
      operative time after MTLTEP and a greater cosmetic satisfaction after SILTEP have
      been found.

PMID- 29362908
TI  - Diagnostic utility of staging abdominal computerized tomography and repeat
      endoscopy in detecting localization errors at initial endoscopy in colorectal
      cancer.
AB  - BACKGROUND: Colonoscopy has a reported localization error rate as high as 21% in
      detecting colorectal neoplasms. Preoperative repeat endoscopy has been shown to
      be protective against localization errors. There is a paucity of literature
      assessing the utility of staging computerized tomography (CT) and repeat
      endoscopy as diagnostic tools for detecting localization errors following initial
      endoscopy. The objective of this study is to determine the diagnostic
      characteristics of staging CT and repeat endoscopy in correcting localization
      errors at initial endoscopy. METHODS: A retrospective cohort study was conducted
      at a large tertiary academic center between January 2006 and August 2014. All
      patients undergoing surgical resection for CRC were identified. Group comparisons
      were conducted between (1) patients that underwent only staging CT (staging CT
      group), and (2) patients that underwent staging CT and repeat endoscopy (repeat
      endoscopy group). The primary outcome was localization error correction rate for
      errors at initial endoscopy. RESULTS: 594 patients were identified, 196 (33.0%)
      in the repeat endoscopy group, and 398 (77.0%) patients in the staging CT group.
      Error rates for each modality were as follows: initial endoscopy 8.8% (95% CI 6.5
      11.0), staging CT 9.3% (95% CI 6.5-11.0), and repeat endoscopy 2.6% (95% CI 0.3
      4.7); p < 0.01. Repeat endoscopy was superior to staging CT in correcting
      localization errors for left-sided / rectal lesions (81.2% vs. 33.3%; p < 0.01),
      right-sided lesions (80.0% vs. 54.5%; p = 0.21), and overall lesions (80.8% vs.
      42.3%; p < 0.01). Repeat endoscopy compared to staging CT demonstrated relative
      risk reduction of 66.7% (95% CI 22-86%), absolute risk reduction of 38.5% (95% CI
      14.2-62.8%), and odds ratio of 0.18 (95% CI 0.05-0.61) for correcting errors at
      initial endoscopy. CONCLUSIONS: Repeat endoscopy in colorectal cancer is superior
      to staging CT as a diagnostic tool for correcting localization-based errors at
      initial endoscopy.

PMID- 29362909
TI  - Gerald J. Marks, M.D., FACS (1925-), founder of the Society of American
      Gastrointestinal Endoscopic Surgeons (SAGES).
AB  - This historical vignette describes the professional career of Gerald J. Marks,
      the founder of the Society of American Gastrointestinal and Endoscopic Surgeons
      and the International Federation of Societies of Endoscopic Surgeons. Dr. Marks
      is also the founding Associate Editor of Surgical Endoscopy, which celebrated its
      30th anniversary in 2017. Dr. Marks is a renowned colorectal surgeon, an
      accomplished watercolor artist, and a fascinating personality.

PMID- 29362910
TI  - Roux-En-Y gastric bypass following failed fundoplication.
AB  - INTRODUCTION: Roux-En-Y gastric bypass (RYGB) is an alternative to reoperative
      fundoplication. The aim of this study was to expand long-term outcomes of
      patients undergoing RYGB after failed fundoplication and assess symptom
      resolution. METHODS: A single institution prospective study was performed of
      patients undergoing fundoplication takedown and RYGB between March 2007 and
      September 2016. Demographics, body mass index (BMI), preoperative symptoms,
      operative duration and findings, and postoperative outcomes were recorded. Data
      were assessed using standard statistical methods. RESULTS: 87 patients with
      failed antireflux surgery underwent RYGB. Median age 58 years (range 25-79
      years). Median preoperative BMI 32.4 kg/m2 (range 21.6-50.6 kg/m2). Comorbidities
      included hypertension (48.3%) and diabetes (11.5%). Sixty-six patients had
      undergone 1 prior fundoplication, 18 had 2 prior fundoplications, and 3 had 3
      prior fundoplications. At least one previous open antireflux procedure had been
      performed in 16.1% of patients. The most common recurrent symptoms were reflux
      (85.1%), dysphagia (36.7%), pain (35.6%), and regurgitation (29.9%). Median
      symptom-free interval from last antireflux surgery was 3 years (range 0-25
      years). RYGB was performed laparoscopically in 47.1% of cases, robotically in
      44.8% of cases, and open in 5.9%. Operative duration was longer in the robotic
      group (p = 0.04). During RYGB, 85.1% patients were found to have an associated
      hiatal hernia, 34.5% had intrathoracic migration of the fundoplication, 32.2% a
      slipped fundoplication onto proximal stomach, and 13.8% had wrap disruption.
      Median length of stay (LOS) was 4 days (range 1-33 days). Median follow-up was
      35.8 months, 11 patients (12.6%) had recurrent reflux symptoms. Excess body
      weight loss (%EWL) was 80.4%. There was no mortality but 8 patients required
      reoperation during follow-up. CONCLUSIONS: Fundoplication takedown with RYGB was
      successful for long-term reflux resolution. Most can be performed via a minimally
      invasive approach with acceptable perioperative morbidity, symptom resolution,
      and the additional benefit of %EWL.

PMID- 29362911
TI  - Use of a novel technique to manage gastrointestinal leaks with endoluminal
      negative pressure: a single institution experience.
AB  - BACKGROUND: Perforations and anastomotic leaks of the gastrointestinal tract are
      severe complications, which carry high morbidity and mortality and management of
      these is a multi-disciplinary challenge. The use of endoluminal vacuum (EVAC)
      therapy has recently proven to be a useful technique to manage these
      complications. We report our institution's experience with this novel technique
      in the chest, abdomen, and pelvis. METHODS: This is a retrospective review of an
      IRB approved registry of all EVAC therapy patients from July 2013 to December
      2016. A total of 55 patients were examined and 49 patients were eligible for
      inclusion: 15 esophageal, 21 gastric, 3 small bowel, and 10 colorectal defects.
      The primary endpoint was closure rate of the GI tract defect with EVAC therapy.
      RESULTS: Fifteen (100%) esophageal defects closed with EVAC therapy. Mean
      duration of therapy was 27 days consisting of an average of 6 endosponge changes
      every 4.8 days. Eighteen (86%) gastric defects closed with EVAC therapy. Mean
      duration of therapy was 38 days with a mean of 9 endosponge changes every 5.3
      days. Three (100%) small bowel defects closed with EVAC therapy. Mean duration of
      therapy was 13.7 days with a mean of 2.7 endosponge changes every 4.4 days. Six
      (60%) colorectal defects closed with EVAC therapy. Mean duration of therapy was
      23.2 days, consisting of a mean of 6 endosponge changes every 4.0 days. There
      were two deaths, which were not directly related to EVAC therapy and occurred
      outside the measured 30-day mortality. CONCLUSION: Our experience demonstrates
      that EVAC therapy is feasible and effective for the management of
      gastrointestinal perforations/leaks throughout the GI tract and can be considered
      as a safe alternative to surgical intervention in select cases.

PMID- 29362912
TI  - Minimally invasive colorectal surgery in the morbid obese: does size really
      matter?
AB  - BACKGROUND: As obesity becomes more prevalent, it presents a technical challenge
      for minimally invasive colorectal resection surgery. Various studies have
      examined the clinical outcomes of obese surgical patients. However, morbidly
      obese patients (BMI >= 35) are becoming increasingly more common. This study aims
      to investigate the short-term surgical outcomes of morbidly obese patients
      undergoing minimal-invasive colorectal surgery and compare them with both obese
      (30 <= BMI < 35) and non-obese patients (BMI < 30). METHODS: Patients from three
      centres who received minimally invasive colorectal surgical resections between
      2006 and 2016 were identified from prospectively collected databases. The
      baseline characteristics and surgical outcomes of morbidly obese, obese and non
      obese patients were analysed. RESULTS: A total of 1386 patients were identified,
      84 (6%) morbidly obese, 246 (18%) obese and 1056 (76%) non-obese. Patients'
      baseline characteristics were similar for age, operating surgeon, surgical
      approach but differed in terms of ASA grade and gender. There was no difference
      in conversion rate, length of stay, anastomotic leak rate and 30-day readmission,
      reoperation and mortality rates. Operation time and blood loss were different
      across the 3 groups (morbidly obese vs obese vs non-obese: 185 vs 188 vs 170 min,
      p = 0.000; 20 vs 20 vs 10 ml, p = 0.003). In patients with malignant disease
      there was no difference in lymph node yield or R0 clearance. Univariate and
      multivariate linear regression analysis showed that for every one-unit increase
      in BMI operative time increases by roughly 2 min (univariate 2.243, 95% CI 1.524
      2.962; multivariate 2.295; 95% CI 1.554-3.036). Univariate and multivariate
      binary logistic regression analyses showed that BMI does not affect conversion or
      morbidity and mortality. CONCLUSIONS: The increased technical difficulty
      encountered in obese and morbidly obese patients in minimally invasive colorectal
      surgery results in higher operative times and blood loss, although this is not
      clinically significant. However, conversion rate and post-operative short-term
      outcomes are similar between morbidly obese, obese and non-obese patients.

PMID- 29362913
TI  - Spatial and temporal patterns of microclimates at an urban forest edge and their
      management implications.
AB  - Fragmented forests generate a variety of forest edges, leading to microclimates
      in the edge zones that differ from those in the forest interior. Understanding
      microclimatic variation is an important consideration for managers because it
      helps when making decisions about how to restrict the extent of edge effects.
      Thus, our study attempted to characterize the changing microclimate features at
      an urban forest edge located on Mt. Gwanak, Seoul, South Korea. We examined edge
      effects on air temperature, relative humidity, soil temperature, soil moisture,
      and photosynthetically active radiation (PAR) during the hottest three
      consecutive days in August 2016. Results showed that each variable responded
      differently to the edge effects. This urban forest edge had an effect on temporal
      changes at a diurnal scale in all microclimate variables, except soil moisture.
      In addition, all variables except relative humidity were significantly influenced
      by the edge effect up to 15 m inward from the forest boundary. The relative
      humidity fluctuated the most and showed the deepest extent of the edge effect.
      Moreover, the edge widths calculated from the relative humidity and air
      temperature both peaked in the late afternoon (16:00 h). Our findings provide a
      reference for forest managers in designing urban forest zones and will contribute
      to the conservation of fragmented forests in urban areas.

PMID- 29362914
TI  - Dysfunctional Wound Healing in Diabetic Foot Ulcers: New Crossroads.
AB  - PURPOSE OF REVIEW: Diabetic foot ulcerations (DFU) affect 25% of patients with
      diabetes mellitus during their lifetime and constitute a major health problem as
      they are often recalcitrant to healing due to a constellation of both intrinsic
      and extrinsic factors. The purpose of this review is to (1) detail the current
      mechanistic understanding of DFU formation and (2) highlight future therapeutic
      targets. RECENT FINDINGS: From a molecular perspective, DFUs exhibit a chronic
      inflammatory predisposition. In addition, increased local hypoxic conditions and
      impaired cellular responses to hypoxia are pathogenic factors that contribute to
      delayed wound healing. Finally, recent evidence suggests a role for epigenetic
      alterations, including microRNAs, in delayed DFU healing due to the complex
      interplay between genes and the environment. In this regard, notable progress has
      been made in the molecular and genetic understanding of DFU formation. However,
      further studies are needed to translate preclinical investigations into clinical
      therapies.

PMID- 29362915
TI  - Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts
      the outcome of T1 high-grade bladder cancer.
AB  - PURPOSE: The identification of factors predicting the outcome of stage T1 high
      grade bladder cancer (BC) is a major clinical issue. METHODS: We performed
      immunohistochemistry to assess the role of human epidermal growth factor receptor
      2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1)
      and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high
      grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone
      or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). RESULTS:
      HER-2 overexpression was a significant predictor of disease-free survival (DFS)
      in the overall as well as in the two patients' population; as for progression
      free survival (PFS), it was significant in the overall but not in the two
      patients' population. MLH1 was an independent predictor of PFS only in patients
      treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most
      importantly, the higher the number of altered markers the lowers the DFS and PFS.
      In multivariate Cox proportional-hazards regression analysis, the number of
      altered molecular markers and BCG treatment were significant predictors (p =
      0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular
      markers was the only significant predictor (p = 0.0054) of PFS. CONCLUSIONS:
      Altered expression of the proto-oncogene HER-2 and the two molecular markers of
      genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the
      higher the number of altered markers the lower the DFS and PFS. These findings
      provide grounds for further testing them in predicting the outcome of this
      challenging disease.

PMID- 29362916
TI  - Decision tree analysis to stratify risk of de novo non-melanoma skin cancer
      following liver transplantation.
AB  - PURPOSE: Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in
      liver transplant (LT) recipients; it behaves more aggressively and it increases
      mortality. We used decision tree analysis to develop a tool to stratify and
      quantify risk of NMSC in LT recipients. METHODS: We performed Cox regression
      analysis to identify which predictive variables to enter into the decision tree
      analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR
      files of September 2016 (n = 102984). RESULTS: NMSC developed in 4556 of the
      105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates
      of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender,
      Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key
      predictive or protective factors for NMSC. These factors were entered into a
      decision tree analysis. The final tree stratified non-Caucasians as low risk
      (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus,
      as high risk (7.3% cumulative incidence of NMSC). The predictions in the
      derivation set were almost identical to those in the validation set (r2 = 0.971,
      p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups
      at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001).
      CONCLUSIONS: The decision tree model accurately stratifies the risk of developing
      NMSC in the long-term after LT.

PMID- 29362917
TI  - Transforming growth factor beta 1 (TGFbeta1) polymorphisms and haplotype
      structures have dual roles in breast cancer pathogenesis.
AB  - PURPOSE: Despite the documented dual role of TGFbeta1 in breast cancer (BC)
      pathogenesis, the subtype-specific influences of its polymorphisms remain
      undocumented. The present study investigated the effects of the TGFB1 promoter
      region (rs1800468 or G-800A and rs1800469 or C-509T) and signal peptide
      (rs1800470 or C29T and rs1800471 or G74C) single nucleotide polymorphisms (SNPs)
      and their haplotype structures on the susceptibility and clinicopathological
      presentation of BC subtypes. METHODS: TGFB1 genotypes were assessed by PCR-RFLP
      and haplotype structures were inferred for 323 BC patients and 405 neoplasia-free
      women, and case-control analyses were performed by logistic regression adjusted
      by age. Clinicopathological parameters (age at diagnosis, tumor size,
      histopathological grade, lymph node metastasis, proliferation index and disease
      stage) were tested for correlation with TGFB1 variants. All statistical analyses
      were two-tailed with an alpha level of 0.05. RESULTS: Variants related to
      increased TGFbeta1 production (C-509T SNP and GTCG haplotype) were associated
      with increased susceptibility to HER2+ tumors and correlated with worse
      prognostic parameters in HER2+ and triple-negative (TN) BCs, but correlated
      negatively to Ki67 in ER/PR+HER2- tumors. Conversely, low TGFbeta1 production
      variants (C29T SNP and GCTG haplotype) were protective against HER2+ tumors and
      correlated negatively with prognostic parameters in HER2+ and TN BCs, while
      indicating higher proliferation rates in ER/PR+HER2- tumors. Furthermore, the
      GCCG haplotype was associated with decreased susceptibility to ER/PR+HER2-
      tumors, but correlated positively with Ki67 in this subgroup. CONCLUSION: The
      present study indicates that TGFB1 variants have subtype-specific roles in BC and
      may switch from tumor suppressor to promoter during tumor development, consistent
      with TGFbeta1 dual role in BC pathogenesis.

PMID- 29362918
TI  - Clinical characteristics and outcomes of cancer patients requiring intensive care
      unit admission: a prospective study.
AB  - PURPOSE: The study was aimed to describe the characteristics of cancer patients
      admitted to the oncological ICU and to identify clinical features associated with
      outcomes. METHODS: This is a prospective study (January 2014 to December 2015) of
      522 cancer patients consecutively admitted to the oncological ICU. Patients with
      a length of oncological ICU stay <= 1 day were excluded. Demographic and clinical
      variables were obtained at oncological ICU admission. The primary outcome of
      interest was hospital mortality. Logistic regression analysis was performed to
      identify independent risk factors for hospital mortality. RESULTS: The study
      cohort consisted of 492 (94.3%) patients with solid tumours and 30 patients
      (5.7%) with haematological malignancies. Advanced cancer was observed in 53.3%.
      Unplanned admission accounted for 25.3%. Hospital mortality rate was 13.0% (n =
      68), and it was higher for patients with unplanned admission than those for
      electively admitted patients (35.6% vs. 5.4; p < 0.0001). Stage IV of cancer (OR
      5.28; 95% CI 2.71-10.28; p < 0.0001), patients from the emergency department (OR
      3.33; 95% CI 1.68-6.61; p = 0.001), unplanned admission (OR 7.99; 95% CI 4.45
      14.33; p < 0.0001), non-malignancy-related admission (OR 5.80; 95% CI 3.26-10.32;
      p < 0.0001), sepsis (OR 4.81; 95% CI 2.28-10.16; p < 0.0001), chemotherapy
      induced adverse event (OR 5.64; 95% CI 2.33-13.66; p < 0.0001), and invasive
      mechanical ventilation (OR 18.70; 95% CI 9.93-35.21; p < 0.0001) were
      independently associated with increased hospital mortality in multivariate
      logistic regression analysis. CONCLUSIONS: ICU admission of cancer patients
      should be based on potential chance of recovering from the acute problem.
      Clinical predictor for mortality could support this purpose (UIN:
      researchregistry3484).

PMID- 29362919
TI  - Proliferation-associated miRNAs-494, -205, -21 and -126 detected by in situ
      hybridization: expression and prognostic potential in breast carcinoma patients.
AB  - PURPOSE: To visualize by in situ hybridization (ISH) the levels of a set of
      proliferation-associated miRNAs and to evaluate their impact and clinical
      applicability in prognostication of invasive breast carcinoma. METHODS: Tissue
      specimen from breast carcinoma patients were investigated for miRNAs-494, -205, 
      21 and -126. Prognostic associations for levels of miRNAs were analyzed based on
      complete clinical data and up to 22.5-year follow-up of the patient material (n =
      285). For detection of the miRNAs, an automated sensitive protocol applying in
      situ hybridization was developed. RESULTS: MiRNA-494 indicated prognostic value
      for patients with invasive breast carcinoma. Among node-negative disease reduced
      level of miRNA-494 predicted 8.5-fold risk of breast cancer death (p = 0.04).
      Altered levels and expression patterns of the studied miRNAs were observed in
      breast carcinomas as compared to benign breast tissue. CONCLUSIONS: The present
      paper reports for the first time on the prognostic value of miRNA-494 in invasive
      breast cancer. Particularly, detection of miRNA-494 could benefit patients with
      node-negative breast cancer in identifying subgroups with aggressive disease.
      Based on our experience, the developed automatic ISH method to visualize altered
      levels of miRNAs-494, -205, -21 and -126 could be applied to routine pathology
      diagnostics providing that conditions of tissue treatment, especially fixation
      delays, are managed.

PMID- 29362920
TI  - Leptomeningeal Metastases.
AB  - OPINION STATEMENT: Treatment options for leptomeningeal metastases are expanding
      with greater tolerability and efficacy than in the past. Improved knowledge of
      molecular subtypes of some cancers can guide in choosing more effective
      therapeutic options; however, physicians should be mindful that these molecular
      types can be different in the central nervous system compared to the rest of the
      body. This is particularly true in breast and lung cancer, in which some patients
      now can live for many months or even years after diagnosis of leptomeningeal
      metastases. Options for intrathecal therapies are expanding, but physicians
      should be mindful that this is a passive delivery system that relies on normal
      CSF flow, so therapies will not penetrate bulky or parenchymal disease sites,
      especially in the presence of abnormal CSF flow. When chemotherapeutic options
      are lacking or unsuccessful, focal radiosurgery which can provide symptomatic
      relief and proton craniospinal radiation remain effective options. Hopefully more
      formal studies will be conducted in the future to verify which treatments are
      indeed most effective for particular types of cancer.

PMID- 29362921
TI  - Cloning, Expression, and Biochemical Characterization of Two New Oligoalginate
      Lyases with Synergistic Degradation Capability.
AB  - Alginate, the most abundant carbohydrate presents in brown macroalgae, has
      recently gained increasing attention as an alternative biomass for the production
      of biofuel. Oligoalginate lyases catalyze the degradation of alginate oligomers
      into monomers, a prerequisite for bioethanol production. In this study, two new
      oligoalginate lyase genes, oalC6 and oalC17, were cloned from Cellulophaga sp.
      SY116, and expressed them in Escherichia coli. The deduced oligoalginate lyases,
      OalC6 and OalC17, belonged to the polysaccharide lyase (PL) family 6 and 17,
      respectively. Both showed less than 50% amino acid identity with all of the
      characterized oligoalginate lyases. Moreover, OalC6 and OalC17 could degrade both
      alginate polymers and oligomers into monomers in an exolytic mode. Substrate
      specificity studies demonstrated that OalC6 preferred alpha-L-guluronate (polyG)
      blocks, while OalC17 preferred poly beta-D-mannuronate (polyM) blocks. The
      combination of OalC6 and OalC17 showed synergistic degradation ability toward
      both alginate polymers and oligomers. Finally, an efficient process for the
      production of alginate monomers was established by combining the new-isolated
      exotype alginate lyases (i.e., OalC6 and OalC17) and the endotype alginate lyase
      AlySY08. Overall, our work provides new insights for the development of novel
      biotechnologies for biofuel production from seaweed.

PMID- 29362923
TI  - Evaluation of an interdisciplinary palliative care inhouse training for
      professionals in gynecological oncology.
AB  - PURPOSE: The aim of this study was to evaluate the effect of a pilot
      interdisciplinary inhouse training in palliative care (PC) for gynecological
      oncologists. METHODS: Competencies of participants from a gynecological
      university department were evaluated taking part in an interdisciplinary PC
      course in a pre and post design. The multiprofessional course covered basic
      principles of PC, symptom management and communication taught by PC specialists.
      Competencies were evaluated using self-designed questionnaires before (ISPG-1),
      right after (ISPG-2), and 6 months after the training (ISPG-3) (inhouse seminar
      palliative care in gynecology: ISPG). RESULTS: 31 persons from the department of
      gynecology took part in the course, of which 27 answered the first questionnaire
      (seven nurses (26%), 19 doctors (71%), one profession not indicated (3%), median
      working experience in gynecological oncology: 5 years). Return rates were: ISPG-1
      27/31 (87.1%), ISPG-2 20/31 (64.5%) and IPSG-3 14/31 (45.2%). A more positive
      attitude towards PC could be observed in the majority of participants after the
      course (ISPG-2 62%, ISPG-3 71%). They felt more competent in the care of
      palliative patients (46%). PC would be initiated earlier and the interaction with
      other disciplines was improved (ISPG-2 85%, ISPG-3 100%). The participants
      assessed a significant improvement of their skills in all palliative fields which
      were analyzed. CONCLUSION: PC inhouse training improves the understanding of PC
      and the interdisciplinary approach in the management of patients with advanced
      disease. It is a feasible and useful instrument to improve the competencies in
      generalist PC of specialists in gynecological oncology.

PMID- 29362922
TI  - Prognostic and clinicopathological significance of PD-L1 in patients with renal
      cell carcinoma: a meta-analysis based on 1863 individuals.
AB  - The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been
      investigated in previous studies; however, the results remain controversial. The
      primary aim of this meta-analysis was to investigate the prognostic and
      clinicopathological significance of the PD-L1 expression in patients with RCC.
      Relevant literature was identified form PubMed, Embase, Web of Science and
      Cochrane library, which compared the prognostic significance between PD-L1
      expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios
      (ORs) for clinical parameters associated with PD-L1 were extracted from eligible
      studies. Heterogeneity was assessed using the I2 value. The fixed-effects model
      was used if there was no evidence of heterogeneity; otherwise, the random-effects
      model was used. Publication bias was evaluated using Begg's funnel plots and
      Egger's regression test. A total of 1863 patients from ten eligible studies were
      analyzed. The results showed that PD-L1 expression is associated with poor
      overall survival in clear cell RCC (ccRCC) (HR = 2.76, 95%CI: 2.25-3.38, I2 =
      14.4%, P < 0.001) and non-clear cell RCC (non-ccRCC) (HR = 2.77, 95%CI: 1.62
      4.72, I2 = 28.8%, P < 0.001). In addition, PD-L1 expression was found to be
      significantly associated with primary tumor stage (OR = 1.76, 95%CI: 1.39-2.23;
      I2 = 56.3%), regional lymph node involvement (OR = 2.10, 95%CI: 1.48-2.98; I2 =
      14.9%), distant metastases (OR = 2.69, 95%CI: 2.05-3.54; I2 = 0.0%), nuclear
      grade (OR = 1.72, 95%CI: 1.32-2.23; I2 = 79.4%) and histologic tumor necrosis (OR
      = 2.25, 95%CI: 1.59-3.18; I2 = 66.1%) in patients with RCC. The outcome stability
      was confirmed by sensitivity analysis. Both the Begg's funnel plot test (P =
      0.276) and the Egger's (P = 0.388) verified that there was no publication bias
      within the included studies. This study suggests that PD-L1 expression is
      correlated with poor prognosis and advanced clinicopathological features in RCC
      patients.

PMID- 29362924
TI  - Ovarian conservation is associated with better survival in young patients with
      T1N0M0 cervical adenocarcinoma: a population-based study.
AB  - PURPOSE: Ovarian conservation is controversial in patients with cervical
      adenocarcinoma due to the risk of ovarian metastasis. The aim of this study is to
      evaluate the association of ovarian conservation with survival outcomes in young
      patients with T1N0M0 cervical adenocarcinoma. METHODS: Women who were 45 years of
      age or younger with T1N0M0 cervical adenocarcinoma from 1988 to 2013 recorded in
      the Surveillance, Epidemiology, and End Results (SEER) database were included.
      Propensity score weighting was used to balance the intragroup differences. Cause
      specific survival (CSS) and overall survival (OS) were compared using Kaplan
      Meier estimates. A multivariate Cox model was used to adjust for covariates
      including propensity score. A stratified analysis was then conducted. RESULTS:
      Totally, 1090 (79.7%) patients underwent oophorectomy and 278 (20.3%) patients
      whose ovaries were preserved were identified. Patients with preserved ovaries
      were younger, with a lower T classification and less likely to undergo pelvic
      lymphadenectomy (all p < 0.05). After propensity weighting, ovarian conservation
      group had better cause-specific survival (CSS) (5-year 98.8 versus 97.1%, 10-year
      98.0 versus 95.2%, p = 0.0370) and overall survival (OS) (5-year 98.8 versus
      97.1%, 10-year 96.5 versus 93.5%, p = 0.0025). After adjustment, the CSS benefit
      of ovarian conservation was marginally significant (p = 0.051) and OS benefit was
      still significant (p = 0.006). Stratified analysis showed that the CSS benefit
      was found in T1b classification (HR, 0.23; 95% CI 0.06-0.89, p = 0.033) and
      histological grade > 1 (HR 0.12; 95% CI 0.02-0.87; p = 0.035). CONCLUSION: Among
      young women with T1N0M0 cervical adenocarcinoma, ovarian conservation is
      associated with better survival.

PMID- 29362925
TI  - A prospective randomized experimental study to investigate the peritoneal
      adhesion formation after waterjet injection and argon plasma coagulation
      (HybridAPC) in a rat model.
AB  - BACKGROUND: This prospective, randomized, controlled, single-blinded study
      investigates the peritoneal adhesion formation of HybridAPC (waterjet elevation
      of the peritoneum with subsequent argon plasma coagulation) versus only waterjet
      (elevation with the same instrument, but without subsequent argon plasma
      coagulation) in a rat model (24 female Wistar rats). MATERIALS AND METHODS:
      Bilateral lesions were created on the abdominal wall with HybridAPC on one
      sidewall and waterjet elevation on the other sidewall of the peritoneum in a
      standard fashion. After 10 days, the rats were euthanized to evaluate the
      peritoneal trauma sites. MAIN OUTCOME MEASURE(S): Adhesion incidence, quantity,
      and quality were scored 10 days postoperatively and studied histopathologically.
      RESULT(S): Incidence of adhesion formation was 2.3% for HybridAPC; no adhesions
      occurred for peritoneal elevation with saline (p = 1.00). Histologic evaluation
      revealed no acute inflammation in both groups. An overall moderate degree of
      granulation tissue formation and myonecrosis was observed in the HybridAPC group,
      whereas no chronic inflammation and myonecrosis occurred after elevation without
      thermal ablation (p < 0.0001). CONCLUSION(S): This study investigates the effect
      of waterjet elevation of the peritoneum with and without subsequent thermal
      ablation on adhesion formation in a rat model for the first time. Peritoneal
      waterjet elevation with saline does not provide any risk of adhesion formation.
      Thermal coagulation with APC after waterjet elevation of the peritoneum creates
      advantageous peritoneal conditions due to a permanent moist tissue surface and
      the cooling effect of the injected solution, resulting in no significant
      difference in adhesion formation compared to peritoneal elevation without thermal
      ablation. HybridAPC can thus be regarded as a beneficial coagulation method with
      only minor adhesion formation due to positive tissue effects of the combined
      waterjet.

PMID- 29362926
TI  - Incidence of echogenic amniotic fluid at term pregnancy and its association with
      meconium.
AB  - PURPOSE: The presence of echogenic amniotic fluid at term gestation on sonography
      is uncommon. The aim of our study was to investigate the incidence of echogenic
      amniotic fluid at term pregnancy, and to determine how often echogenic amniotic
      fluid was associated with meconium. METHODS: All singleton pregnant women at term
      who were admitted to our labor unit and who delivered within 24 h of the
      ultrasound scan were included in the study. For each woman, gestational age,
      maternal age, gravidity, parity, the character of the amniotic fluid on
      ultrasound at admission (clear or echogenic), birth weight, and the character of
      the amniotic fluid on artificial or spontaneous rupture of membranes or on
      cesarean section (clear/with vernix/meconium-stained) were recorded. RESULTS:
      When amniotic fluid was assessed on ultrasound, among 278 patients, 9 (3.2%)
      patients' amniotic fluid was echogenic. When the amniotic fluid was assessed at
      delivery, the rates of meconium-stained amniotic fluid in women with and without
      echogenic amniotic fluid were 44.44% (4/9) and 9.3% (25/269), respectively; the
      difference was statistically significant (p = 0.035). We found a sensitivity and
      specificity of 13.79 and 97.99%, and a positive and negative predictive value of
      44.44 and 90.7%, respectively, for echogenic amniotic fluid seen on ultrasound in
      identifying meconium-stained amniotic fluid. CONCLUSIONS: The incidence of
      echogenic amniotic fluid at term gestation was found as 3.2 and 44.4% of cases of
      echogenic amniotic fluid was associated with meconium.

PMID- 29362927
TI  - Endoscopic ultrasonography (EUS)-guided laser ablation (LA) of adrenal metastasis
      from pancreatic adenocarcinoma.
AB  - Endoscopic ultrasonography (EUS)-guided laser ablation (LA) is potentially
      applicable to tumours in the left lobe of the liver and pancreas. This report
      seeks to introduce the novel use of EUS-guided LA for left adrenal metastases
      from pancreatic adenocarcinoma. A 70-year-old female was referred to our hospital
      for dull abdominal pain and tiredness for 1 month. Computed tomography (CT)
      discovered a 1.0 * 1.7 cm mass in the area of the left adrenal gland. The lesion
      was highly suspicious for metastasis due to her history of pancreatic
      adenocarcinoma 1 year ago, which was removed through radical surgery.
      Intraoperative frozen-section pathology revealed a tumour invading the left
      adrenal gland. The left adrenal mass was clearly visualised on EUS and exhibited
      irregular hyper-enhancement during contrast. The tumour was successfully treated
      by four sessions of EUS-guided LA. After the procedure, symptomatic relief was
      achieved and remained. At the 4-month follow-up, contrast-enhanced CT revealed
      that the volume of the target was significantly decreased. Here, we introduced a
      new method for left adrenal metastasis using thermal ablation through EUS. As a
      potential alternative access to the percutaneous approach, EUS-guided LA may
      provide a minimally invasive treatment to relieve the tumour burdens and symptoms
      when applied accurately.

PMID- 29362928
TI  - Is amalgamated ligno-bupivacaine an answer to complicated minor oral surgical
      anesthesia? A randomized split-mouth double-blind clinical trial.
AB  - PURPOSE: The purpose of this study was to find a suitable anesthetic combination
      for complicated and protracted minor oral surgical procedures. METHODS: Fifty
      patients with bilaterally impacted deep-seated mandibular third molars were
      included in this study and randomly divided on the basis of anesthetic used into
      two groups. Group A received 2% lignocaine with 1:200,000 adrenaline while in
      group B, amalgamated mixture of 2% lignocaine and 0.5% bupivacaine was used. The
      onset time, duration of anesthetic effect, supplementary injections, pain (during
      local anesthetic deposition, intra and postoperatively), and postoperative
      analgesia were the study parameters. Chi-square and unpaired t tests were used to
      compare means. RESULTS: The onset time in both the groups was comparable and
      showed statistically significant difference between the duration of anesthetic
      effect with notable requirement of supplemental anesthetic injections in group A
      (54%) (p < 0.05). Pain scores also revealed a statistically significant
      intergroup difference (p < 0.05). Requirement of postoperative analgesics was
      delayed in group B. CONCLUSIONS: The amalgamated mixture of lignocaine and
      bupivacaine had equivocally rational onset and provided a more profound and in
      depth anesthesia especially in complicated and protracted minor oral surgical
      procedures. Though this mixture is widely used in other surgical fields, its
      efficacy still remains unexploited and undocumented in oral and maxillofacial
      surgical procedures.

PMID- 29362929
TI  - Does the efficacy of parent-child training depend on maternal symptom
      improvement? Results from a randomized controlled trial on children and mothers
      both affected by attention-deficit/hyperactivity disorder (ADHD).
AB  - Multimodal treatment of children with ADHD often includes parent-child training
      (PCT). However, due to the high heritability, parents of children with ADHD are
      frequently also affected by the disorder, which is likely to constitute a
      significant barrier to successful treatment of the child. This secondary analysis
      of our randomized controlled multicentre AIMAC trial (ADHD in mothers and
      children) investigates whether children's outcomes following parent-child
      training in combination with maternal ADHD treatment depend on maternal symptom
      improvement. In a first step focusing on treatment of maternal ADHD, 144 mothers
      of mother-child dyads were randomized to multimodal ADHD treatment (group
      psychotherapy plus methylphenidate) or clinical management (mainly supportive
      counselling). After 12 weeks (T2), a 12-week PCT program (T2-T3) for all mother
      child dyads was added to treat children's ADHD. Maternal symptomatology (CAARS
      O:L; SCL-90-R) and children's externalizing symptoms (ADHD-ODD Scale, SDQ) were
      repeatedly assessed (T1 = baseline, T2, T3). Effects of changes in maternal
      symptomatology (T1-T2) on the change in children's symptom scores (T1-T3) were
      analysed using a general linear model, controlling for baseline scores, study
      centre, and maternal treatment group. 125 mother-child dyads were analysed.
      Mothers showed significant improvements in ADHD symptoms and overall
      psychopathology [CAARS-O:L ADHD index: mean - 3.54, SE 0.74 p < 0.0001; SCL-90-R
      Global Severity (GS): mean - 11.03, SE 3.90, p = 0.0056]. Although children's
      externalizing symptoms improved significantly (ADHD-ODD Scale: mean - 4.46, SE
      0.58, p < 0.0001), maternal improvement had no effect on children's outcomes
      after Bonferroni-Holm correction for multiple testing. The findings do not
      support our hypothesis that children's outcomes following PCT for ADHD depend on
      maternal symptom improvements.Trial register CCT-ISRCTN73911400.

PMID- 29362930
TI  - Molecular prevalence of bovine noroviruses and neboviruses in newborn calves in
      Iran.
AB  - In this study, bovine enteric caliciviruses (BECs) were detected in 49.4% of a
      total of 253 stool specimens for diarrheic calves collected from 42 industrial
      dairy farms from March 2010 to February 2012. Genogroup III norovirus (NoVsGIII)
      were more prevalent (39.5%) than neboviruses (NBs) (15%), and coinfections were
      observed in 5.1% of the samples tested. Sequence analysis of the partial
      polymerase gene from 13 NoVsGIII samples indicated the circulation of both
      genotype 1 and genotype 2 strains. Among the six NB strains sequenced, five were
      related to the Bo/Nebraska/80/US strain, while one was related to the
      Bo/Newbury1/76/UK strain.

PMID- 29362931
TI  - Immunoregulation of Theiler's virus-induced demyelinating disease by glatiramer
      acetate without suppression of antiviral immune responses.
AB  - While most disease-modifying drugs (DMDs) regulate multiple sclerosis (MS) by
      suppressing inflammation, they can potentially suppress antiviral immunity,
      causing progressive multifocal leukoencephalopathy (PML). The DMD glatiramer
      acetate (GA) has been used for MS patients who are at high risk of PML. We
      investigated whether GA is safe for use in viral infections by using a model of
      MS induced by infection with Theiler's murine encephalomyelitis virus (TMEV).
      Treatment of TMEV-infected mice with GA neither enhanced viral loads nor
      suppressed antiviral immune responses, while it resulted in an increase in the
      Foxp3/Il17a ratio and IL-4/IL-10 production. This is the first study to suggest
      that GA could be safe for MS patients with a proven viral infection.

PMID- 29362932
TI  - Increased rate of ventriculostomy-related hemorrhage following endovascular
      treatment of ruptured aneurysms compared to clipping.
AB  - OBJECTIVE: Acutely ruptured aneurysms can be treated by endovascular intervention
      or via surgery (clipping). After endovascular treatment, the risk of
      thromboembolic complications is reduced by the use of anticoagulative agents,
      which is not required after clipping. The aim of the study is to investigate the
      rate of ventriculostomy-related hemorrhage after endovascular treatment and
      clipping. METHODS: A consecutive series of 99 patients treated for a ruptured
      aneurysm which required an external ventricular drainage between 2010 and 2015
      were included. Their CT scans were investigated retrospectively for
      ventriculostomy-related hemorrhage. Furthermore, the extent of bleeding, the rate
      of revision surgery, and the rate of bacterial ventriculitis have been analyzed.
      RESULTS: Ventriculostomy-related hemorrhage was observed in 20 of 45 patients
      after endovascular treatment compared to 7 of 54 patients after clipping (chi
      squared test, p < 0.001). Revision surgery was indicated in 75%. In 50% of these
      patients, revision surgery was required more than once and nearly 50% developed
      additional cerebral infections. Intraventricular or intracerebral extension of
      the bleeding was observed only in the endovascular treatment group (chi-squared
      test, p = 0.003). Glasgow outcome scale showed a significant better outcome in
      the surgical group (t test, p = 0.005). CONCLUSIONS: Ventriculostomy-related
      hemorrhage is an underestimated complication after endovascular treatment leading
      to revision surgeries, bacterial infections, and may have a negative impact on
      long-term outcome. The probability of occurrence is increased when
      anticoagulation is performed by heparin in combination with antiplatelet drugs as
      compared to heparin alone. Lumbar drainage should be considered as an alternative
      for treatment of acute hydrocephalus in patients with Hunt and Hess grade 1-3.

PMID- 29362933
TI  - Supplementary motor area syndrome after surgery for parasagittal meningiomas.
AB  - BACKGROUND: Resection within the supplementary motor area (SMA) may be
      accompanied by dramatic motor deficits and speech arrest when the dominant
      hemisphere is involved, termed the SMA syndrome. Typically, the muscle tone of
      the paralyzed extremities is preserved, and in most cases, a complete or near
      complete recovery is seen within a few months. The SMA syndrome has not been
      recognized for extra-axial tumor surgery in approximation of the SMA. METHODS: We
      observed the SMA syndrome in a patient operated for a parasagittal meningioma in
      the posterior frontal region, and this observation intrigued us to prospectively
      collect similar cases. RESULTS: In the period from January 2010 to December 2015,
      we observed five patients who developed a partial SMA syndrome after surgery for
      frontal parasagittal meningiomas. The muscle tone was preserved in the affected
      extremities. All patients experienced improvement in motor function within a few
      days, and on follow-up, three out of five patients had recovered completely.
      Three of the patients had meningioma WHO grade II. CONCLUSIONS: Surgically
      induced SMA syndrome can easily be confused with pyramidal weakness. This series
      of cases demonstrate that the syndrome may also develop after removal of extra
      axial tumors and is probably underdiagnosed and underreported. The good
      functional prognosis is helpful in the preoperative counseling and follow-up of
      these patients.

PMID- 29362934
TI  - Effect of heat stress on contractility of tissue-engineered artificial skeletal
      muscle.
AB  - The effects of heat stress on tissue like skeletal muscle have been widely
      studied. However, the mechanism responsible for the effect of heat stress is
      still unclear. A useful experimental tissue model is necessary because muscle
      function in cell culture may differ from native muscle and measuring its
      contractility is difficult. We previously reported three-dimensional tissue
      engineered artificial skeletal muscle (TEM) that can be easily set in a
      measurement apparatus for quantitative evaluation of contractility. We have now
      applied TEM to the investigation of heat stress. We analyzed contractility
      immediately after thermal exposure at 39  degrees C for 24 or 48 h to evaluate
      the acute effects and after thermal exposure followed by normal culture to
      evaluate the aftereffects. Peak twitch contractile force and time-to-peak twitch
      were used as contractile parameters. Heat stress increased the TCF in the early
      stage (1 week) after normal culture; the TCF decreased temporarily in the middle
      to late stages (2-3 weeks). These results suggest that heat stress may affect
      both myoblast fusion and myotube differentiation in the early stage of TEM
      culture, but not myotube maturation in the late stage. The TCF increase rate with
      thermal exposure was significantly higher than that without thermal exposure.
      Although detailed analysis at the molecular level is necessary for further
      investigation, our artificial skeletal muscle may be a promising tool for heat
      stress investigation.

PMID- 29362935
TI  - Two-Dimensional Spectroscopy at Terahertz Frequencies.
AB  - Multidimensional spectroscopy in the visible and infrared spectral ranges has
      become a powerful technique to retrieve dynamic correlations and couplings in
      wide-ranging systems by utilizing multiple correlated light-matter interactions.
      Its extension to the terahertz (THz) regime of the electromagnetic spectrum,
      where rich material degrees of freedom reside, however, has been progressing
      slowly. This chapter reviews some of the THz-frequency two-dimensional (2D)
      spectroscopy techniques and experimental results realized in recent years.
      Examples include gas molecule rotations, spin precessions in magnetic systems,
      and liquid molecular dynamics studied by 2D THz or hybrid 2D THz-Raman
      spectroscopy techniques. The methodology shows promising applications to
      different THz-frequency degrees of freedom in various chemical systems and
      processes.

PMID- 29362936
TI  - Arginine-alpha, beta-dehydrophenylalanine Dipeptide Nanoparticles for pH
      Responsive Drug Delivery.
AB  - PURPOSE: Nanoparticles (NPs) exhibiting responsiveness towards pH variations in
      organs, tissue microenvironments and cellular compartments can significantly add
      on to the drug delivery potential. Here, we have developed NPs from an
      amphipathic dipeptide, Arginine-alpha, beta-dehydrophenylalanine (RDeltaF), and
      tried to explore their pH responsive drug delivery potential in various cancer
      cells. METHODS: RDeltaF-NPs were architectured by harnessing the process of
      molecular self-assembly followed by the assessment of effect of pH on NPs
      morphology using zetasizer, SEM and CD. FTIR and PXRD analysis of the dipeptide
      and doxorubicin (Dox) were carried out for compatibility assessment followed by
      encapsulation of Dox in RDeltaF-NPs. RDeltaF-Dox-NPs were evaluated for pH
      dependent release as well as for in-vitro cellular internalization and efficacy
      in cancer cells. RESULTS: RDeltaF self-assembled to form monodispersed particles
      at pH 7. SEM analysis revealed a loss of overall particle morphology along with
      particle aggregation at highly acidic and basic pH respectively. The NPs
      demonstrated a slow and sustained release behaviour at pH 7 (97.64 +/- 4.71%
      after 36 h) in comparison to pH 2 (90.27 +/- 1.45% after 8 h) and pH 10 (96.39 +/
      3.87% after 12 h). In-vitro efficacy studies carried-out in various cancer cells
      revealed that RDeltaF-Dox-NPs exhibited higher efficacy with 1.65, 1.95 and 13.34
      fold lower IC50 values in comparison to Dox in C6, HCT-116 and AGS cell lines.
      CONCLUSIONS: RDeltaF-Dox-NPs with higher drug release at acidic pH, enhanced
      internalization in cancer cells along with higher cytotoxic potential can act as
      effective pH responsive drug delivery systems.

PMID- 29362937
TI  - Relapse rate and predictors of relapse in a large single center cohort of type 1
      autoimmune pancreatitis: long-term follow-up results after steroid therapy with
      short-duration maintenance treatment.
AB  - BACKGROUND: Type 1 autoimmune pancreatitis (AIP), as a pancreatic manifestation
      of IgG4-related disease, shows a favorable prognosis in the short term. However,
      disease relapse is common in long-term follow-up, despite a successful initial
      treatment response. This study aimed to identify the predictors of relapse and
      long-term outcomes in patients with type 1 AIP. METHODS: Patients with more than
      2 years of follow-up who met the International Consensus Diagnostic Criteria for
      type 1 AIP were included. Patients who had undergone pancreatic operations
      associated with AIP or who lacked sufficient clinical data were excluded.
      RESULTS: All 138 patients achieved clinical remission with initial steroid
      therapy, and 66 (47.8%) experienced relapse during a median 60 (range 24-197)
      months follow-up. Among the relapsed patients, about 74% (49/66) relapsed within
      3 years. About 60% (82/138) had other organ involvement (OOI), most commonly in
      the proximal bile duct (26.8%). At first diagnosis, OOI, and especially OOI of
      the proximal bile duct, was a significant independent predictor of relapse
      (hazard ratio 2.65; 95% confidence interval 1.44-4.89; p = 0.002), according to
      multivariate analysis. During the follow-up period, 16 (11.6%) patients
      experienced endocrine/exocrine dysfunction and 32 (23.2%) patients developed de
      novo pancreatic calcifications/stones. No pancreatic cancer occurred in any
      patients. CONCLUSIONS: Type 1 AIP has common relapses, and patients with OOI,
      especially OOI of the proximal bile duct, appear to be at increased risk for
      relapse. Long-term sequelae, including pancreatic insufficiency and pancreatic
      calcifications/stones, are common in patients with relapse. To reduce the
      relapse, longer maintenance treatment may be needed especially for patients at
      high risk for relapse.

PMID- 29362938
TI  - Statin use and pancreatic cancer risk in two prospective cohort studies.
AB  - BACKGROUND: Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      inhibitors, are common lipid-lowering agents and may reduce the risk of several
      cancer types including pancreatic cancer. However, the association between statin
      use and pancreatic cancer risk has not been fully evaluated in prospective
      studies. METHODS: We studied the association between statin use and incident
      pancreatic cancer in 113,059 participants from the prospective Nurses' Health
      Study and Health Professionals Follow-up Study. Statin use was self-reported via
      study questionnaires and updated biennially. Hazard ratios (HRs) and 95%
      confidence intervals (CIs) for incidence of pancreatic cancer were estimated
      using multivariable Cox proportional hazards models with adjustment for potential
      confounders. RESULTS: In total, 583 participants developed incident pancreatic
      cancer during 1.4 million person-years of follow-up. No difference was identified
      in pancreatic cancer risk for regular versus non-regular statin users
      (multivariable-adjusted HR 0.98; 95% CI 0.82-1.16). There was no significant
      heterogeneity in the association of statin use with pancreatic cancer risk
      between the cohorts. Similarly, longer duration of regular statin use was not
      associated with decreased risk of pancreatic cancer (Ptrend = 0.65). The results
      remained similar when we examined statin use status at baseline or accounting for
      4-year latency period. We observed no statistically significant effect
      modification for the association of statin use with pancreatic cancer risk by
      body mass index, smoking status, or diabetes mellitus status (all Pinteraction >
      0.21). CONCLUSIONS: Regular statin use was not associated with pancreatic cancer
      risk in two large prospective cohort studies in the U.S.

PMID- 29362939
TI  - Human development index, children's health-related quality of life and movement
      behaviors: a compositional data analysis.
AB  - PURPOSE: Health-related quality of life has been related to physical activity,
      sedentary behavior, and sleep among children from developed nations. These
      relationships have rarely been assessed in developing nations, nor have behaviors
      been considered in their true context, as mutually exclusive and exhaustive parts
      of the movement behavior composition. This study aimed to explore whether
      children's health-related quality of life is related to their movement behavior
      composition and if the relationship differs according to human development index.
      METHODS: Children aged 9-11 years (n = 5855), from the 12-nation cross-sectional
      observational International Study of Childhood Obesity, Lifestyle and the
      Environment 2011-2013, self-reported their health-related quality of life
      (KIDSCREEN-10). Daily movement behaviors were from 24-h, 7-day accelerometry.
      Isometric log-ratio mixed-effect linear models were used to calculate estimates
      for difference in health-related quality of life for the reallocation of time
      between daily movement behaviors. RESULTS: Children from countries of higher
      human development index reported stronger positive relationships between health
      related quality of life and moderate-to-vigorous physical activity, relative to
      the remaining behaviors (r = 0.75, p = 0.005) than those from lower human
      development index countries. In the very high human development index strata
      alone, health-related quality of life was significantly related to the movement
      behavior composition (p = 0.005), with moderate-to-vigorous physical activity
      (relative to remaining behaviors) being positively associated with health-related
      quality of life. CONCLUSIONS: The relationship between children's health-related
      quality of life and their movement behaviors is moderated by their country's
      human development index. This should be considered when 24-h movement behavior
      guidelines are developed for children around the world.

PMID- 29362942
TI  - Is Salvage of Recently Infected Breast Implant After Breast Augmentation or
      Reconstruction Possible? An Experimental Study.
AB  - INTRODUCTION: The reinsertion of an infected implant when peri-prosthetic
      infection occurs early after breast augmentation or breast reconstruction remains
      controversial. In this experimental study, the authors tried to remove bacteria,
      and their biofilm, from the colonized surface of breast prostheses, without
      damaging their integrity. MATERIALS AND METHODS: A total of 112 shell samples of
      silicone breast prostheses, smooth (SPSS) and textured (TPSS), were colonized by
      S. epidermidis (SE) or S. aureus (SA) strains, all able to produce biofilms.
      After 15 days, all the samples were removed from the contaminated culture broth
      and constituted 4 groups of 20 contaminated samples: SPSS/SE (group I), SPSS/SA
      (group II), TPSS/SE (group III), TPSS/SE (group IV). In another group-group SEM-,
      16 colonized samples were used for documentation with scanning electron
      microscopy (SEM). The remaining 16 samples were used to test the limits of
      detection of the sterility test. All samples of groups I-IV and 8 samples of
      group SEM were " washed " with a smooth brush in a povidone-iodine bath and
      rinsed with saline solution. A subset of the washed samples was sent for SEM and
      the others were immersed in sterile broth and were incubated at 35  degrees C for
      3 weeks (groups I-IV). RESULTS: Fifteen days after contamination, all the samples
      in groups I-IV were colonized. In the SEM group, SEM images attested to the
      presence of bacteria in biofilm attached to the shells. After cleaning, SEM did
      not reveal any bacteria and there was no visible alteration in the outer
      structure of the shell. Sterility tests performed after decontamination in groups
      I-IV remained negative for all the samples. CONCLUSION: Breast prostheses
      recently contaminated with Staphylococci, frequently involved in peri-prosthetic
      breast implant infection and capable of producing biofilms, can be efficiently
      decontaminated by the procedure used in this study. Our decontamination procedure
      did not alter the surface structure of the prostheses. This decontamination
      procedure could allow reinsertion of an infected implant when peri-prosthetic
      infection occurs early after breast augmentation or breast reconstruction and
      when a salvage procedure is indicated. NO LEVEL ASSIGNED: This journal requires
      that authors assign a level of evidence to each submission to which Evidence
      Based Medicine rankings are applicable. This excludes Review Articles, Book
      Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver
      Studies, and Experimental Studies. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 29362943
TI  - Laser-Assisted Liposuction (LAL) Versus Traditional Liposuction: Systematic
      Review.
AB  - INTRODUCTION: Liposuction is the most performed surgical procedure in Brazil and
      the second in the world. In recent years, new technologies have been developed in
      an attempt to improve liposuction, such as laser. The objective of this study is
      to evaluate the efficacy and safety of laser-assisted liposuction (LAL) compared
      to traditional liposuction through a systematic review of the literature. METHOD:
      The search strategy used was the combination of the descriptors [lasers (MeSH
      Terms)] and (lipectomy [MeSH Terms]) in the PubMed database. Two independent
      researchers carried out the reading of the abstracts and selection of the studies
      according to the eligibility criteria. The risks of study bias were evaluated
      using an instrument similar to that used by the Cochrane Collaboration. RESULTS:
      Initially, 80 studies were obtained and, after evaluating the eligibility
      criteria, seven remained. Five of them observed that LAL has benefits when
      compared to traditional liposuction, and the main outcomes were compared with
      regard to histological analysis (2 products), further reduction of subcutaneous
      fat (2), better retraction of the skin (3), and higher personal satisfaction of
      the patient (2). The qualitative assessment identified high risks of bias in
      various areas in the studies. CONCLUSION: Although studies have concluded that
      LAL promotes greater fat reduction, better skin retraction, and greater patient
      satisfaction compared to traditional liposuction, the high bias impedes a more
      reliable conclusion. LEVEL OF EVIDENCE III: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266 .

PMID- 29362940
TI  - The H-Reflex as a Biomarker for Spinal Disinhibition in Painful Diabetic
      Neuropathy.
AB  - PURPOSE OF REVIEW: Neuropathic pain may arise from multiple mechanisms and
      locations. Efficacy of current treatments for painful diabetic neuropathy is
      limited to an unpredictable subset of patients, possibly reflecting diversity of
      pain generator mechanisms, and there is a lack of targeted treatments for
      individual patients. This review summarizes preclinical evidence supporting a
      role for spinal disinhibition in painful diabetic neuropathy, the physiology and
      pharmacology of rate-dependent depression (RDD) of the spinal H-reflex and the
      translational potential of using RDD as a biomarker of spinally mediated pain.
      RECENT FINDINGS: Impaired RDD occurs in animal models of diabetes and was also
      detected in diabetic patients with painful vs painless neuropathy. RDD status can
      be determined using standard neurophysiological equipment. Loss of RDD may
      provide a clinical biomarker of spinal disinhibition, thereby enabling a
      personalized medicine approach to selection of current treatment options and
      enrichment of future clinical trial populations.

PMID- 29362944
TI  - Assessment of Pb, Cd and Hg soil contamination and its potential to cause
      cytotoxic and genotoxic effects in human cell lines (CaCo-2 and HaCaT).
AB  - Soil contamination by heavy metals is a serious global environmental problem,
      especially for developing countries. A large number of industrial plants, which
      continually pollute the environment, characterize Tuzla Canton, Bosnia and
      Herzegovina. The aim of this study was to assess the level of soil pollution by
      heavy metals and to estimate cytotoxicity and genotoxicity of soil leachates from
      this area. Lead (Pb), cadmium (Cd) and mercury (Hg) were analyzed by ICP-AES and
      AAS. Soil contamination was assessed using contamination factor, degree of
      contamination, geoaccumulation index and pollution load index. To determine the
      connection of variables and understanding their origin in soils, principal
      component analysis (PCA) and cluster analysis (CA) were used. The results
      indicate that Cd and Hg originated from natural and anthropogenic activities,
      while Pb is of anthropogenic origin. For toxicity evaluation, CaCo-2 and HaCaT
      cells were used. PrestoBlue assay was used for cytotoxicity testing, and
      gammaH2A.X for genotoxicity evaluation. Concerning cytotoxicity, Cd and Hg had a
      positive correlation with cytotoxicity in HaCaT cells, but only Hg induced
      cytotoxicity in CaCo-2 cells. We also demonstrate that soil leachates
      contaminated by heavy metals can induce genotoxicity in both used cell lines.
      According to these results, combining bioassays with standard physicochemical
      analysis can be useful for evaluating environmental and health risks more
      accurately. These results are important for developing proper management
      strategies to decrease pollution. This is one of the first studies from this area
      and an important indication of soil quality in Southeast Europe.

PMID- 29362945
TI  - Increasing Stroke Knowledge and Decreasing Stroke Risk in a Latino Immigrant
      Population.
AB  - Stroke knowledge is poor and stroke risk is growing for the U.S. Latino immigrant
      population. We present results of an evaluation of a tailored, community-based
      intervention in Durham, North Carolina. The intervention included integration of
      stroke knowledge into classes and workshops at a community-based organization.
      Knowledge surveys were administered to participants immediately before and after
      stroke education, and at multiple points over the following year. For both low
      risk participants receiving classroom-based education and individually care
      managed participants with risk factors, stroke knowledge improved dramatically
      and remained high among those who could be reached for follow-up. Evidence of
      behavior change and change in clinical status was weak. These findings from an
      observational study conducted in a real-world context complement the results of
      previously reported efficacy studies, indicating potential gains from health
      education for Latino immigrants, even from classroom-based education for low-risk
      individuals.

PMID- 29362946
TI  - Prevalence and Risk Factors Associated with Self-Rated Morbidities Among South
      Asian Migrant Gas Station Workers in Kuwait.
AB  - Gas station workers (GSWs) are at elevated risk of morbidities associated with
      exposure to petrochemical substances. This cross-sectional study assessed the
      prevalence and examined demographics and occupation-related risk factors
      associated with self-rated ill-health among GSWs in Kuwait. Structured
      questionnaire was used to record self-rated ill-health from 460 selected GSWs of
      South-Asian origin. Prevalence of self-rated ill-health conditions was computed.
      Random-intercept multivariable logistic regression model was used to identify the
      demographics and/or work-place related potential risk factors associated with one
      or more morbidities. Prevalent morbidities were eye(s) complaint (45.2%),
      asthma/shortness of breath (7.6%), frequent sneezing and allergic rhinitis
      (44.3%), recurrent headache (48.3%), dizziness (9.8%), tremors (42%), and
      eczema/skin complaint (44.1%). Furthermore, GSWs were significantly more likely
      to report one or more ill-health conditions (vs. none), if they were
      overweight/obese (aOR 1.8; 95% CI 1.1-2.9), married (aOR 2.6; 95% CI 1.5-4.5) or
      on current job for more than one year (aOR 6.4; 95% CI 2.9-15.4). In conclusion,
      GSWs suffer from ailments of multiple organ systems and need education and
      facilitation for self-protection.

PMID- 29362947
TI  - Morphological characterization of pulmonary microvascular disease in
      bronchopulmonary dysplasia caused by hyperoxia in newborn mice.
AB  - PURPOSE: Pulmonary microvascular injury is associated with the pathogenesis of
      bronchopulmonary dysplasia (BPD). To characterize the mechanisms of pulmonary
      vascular disease resulting from BPD, we studied the ultrastructural changes
      affecting pulmonary microvasculature. METHODS: Newborn ICR mice were exposed to
      85% hyperoxia or normoxia for 14 days, and then normal air replacement conditions
      for the following 7 days. At postnatal day (P)14 and P21, lungs were harvested
      for ultrastructural examination and assessment of pulmonary hypertension.
      RESULTS: The ultrastructure of pulmonary microvasculature in the hyperoxia
      exposed lungs revealed a collapsed capillary lumen. This was due to the abnormal
      morphology of endothelial cells (ECs) characterized by heterogeneously thick
      cytoplasm. Compared to normal air controls, the specimens displayed also
      remarkably thick blood-air barriers (BABs), most of which were occupied by EC
      layer components. Structural changes were accompanied by increased pulmonary
      artery medial thickness and right ventricular hypertrophy (RVH). Moreover,
      abnormalities in ECs persisted even after exposure to 7 days of normal air
      replacement conditions. Results were confirmed by morphometric quantification.
      CONCLUSION: Our results suggest that the abnormal morphology of capillary ECs and
      thick BABs correlates with pulmonary artery remodeling and RVH. These
      ultrastructural changes might represent possible mechanisms of secondary
      pulmonary hypertension in BPD.

PMID- 29362948
TI  - Genetic Counselors' Experiences and Interest in Telegenetics and Remote
      Counseling.
AB  - In 2009, the National Society of Genetic Counselors Service (NSGC) Delivery Model
      Task Force defined genetic counseling service delivery models including telephone
      (genetic counseling provided remotely by telephone) and telegenetics (counseling
      provided remotely using videoconferencing). Little is known about the experience
      of genetic counselors practicing telemedicine in the USA. We sought to evaluate
      perceived satisfaction, advantages, disadvantages, and barriers to the practice
      and implementation of telegenetics by practicing genetic counselors. A 21
      question online survey was distributed via the NSGC's member directory.
      Descriptive statistics and a thematic analysis were used to analyze data. A total
      of 344 surveys were completed of which 235 (68.3%) respondents had delivered
      genetic counseling via telemedicine and 109 (36.6%) had not. Overall genetic
      counseling providers who had provided telegenetics were satisfied or very
      satisfied with their position (91%) and those who were not performing
      telegenetics were at least slightly interested in a telehealth position (92%).The
      most common appealing reasons for working in or wanting to work in telemedicine
      included an innovative approach to healthcare delivery, aspects of remote
      positions such as the ability to work from home, and flexibility of hours.
      Unappealing characteristics of telemedicine included the inability to see
      nonverbals, limited psychosocial counseling, and limited social interaction with
      colleague that is associated with remote positions. Barriers to implementation of
      telegenetics were noted by 53% of respondents with the largest barrier being
      billing and reimbursement. The results of this work suggest that telegenetics
      service organizations could consider increasing social interactions, attempting
      to use the preferred method of care (video) to increase ability to see
      nonverbals, offering flexible work hours, and allowing time to address
      psychosocial issues as they arise in consultations.

PMID- 29362950
TI  - Aspirin therapy discontinuation and intraoperative blood loss in spinal surgery:
      a systematic review.
AB  - The purpose of this study was to determine the effect of aspirin therapy
      discontinuation on intraoperative blood loss in spinal surgery. We searched
      Medline and Google Scholar 1946 to January 2017 inclusive for case-control
      studies, cohort studies, and controlled trials reporting intraoperative blood
      loss during spinal surgery in patients on pre-operative aspirin. Other outcome
      measures reported in the eligible studies were collected as secondary outcomes.
      Two reviewers independently screened and extracted data from each study. Five
      retrospective cohort and two case-control studies were eligible for inclusion. Of
      the 1173 patients identified, 587 patients were never on aspirin (Ax), 416
      patients had aspirin discontinued before surgery (Ad), ranging from 3 to 10 days,
      and 170 patients had aspirin continued until surgery (Ac). Six out of seven
      studies reported no statistically significant difference in intraoperative blood
      loss irrespective of aspirin discontinuation. Meta-analysis was not possible due
      to high risk of bias. Of the secondary outcome measures, operative time and
      postoperative complications were most commonly reported. One of six studies
      evaluating operative time reported a significantly longer operative time in the
      Ad group compared with the Ac group. The overall risk of postoperative haematoma
      in Ax, Ad, and Ac groups is 0.2% (n/N = 1/587), 0.2% (n/N = 1/416), and 1.2% (n/N
      = 2/170), respectively. No study reported a statistically significant difference
      in postoperative complications. There is no strong evidence demonstrating a
      difference in intraoperative blood loss, operation time, and postoperative
      complications, irrespective of aspirin discontinuation. This is, however, based
      on a limited number of studies and higher-quality research is required to answer
      this question with a higher degree of confidence.

PMID- 29362949
TI  - Chemical Ecology of Chemosensation in Asteroidea: Insights Towards Management
      Strategies of Pest Species.
AB  - Within the Phylum Echinodermata, the class Asteroidea, commonly known as starfish
      and sea stars, encompasses a large number of benthos inhabiting genera and
      species with various feeding modalities including herbivores, carnivores,
      omnivores and detritivores. The Asteroidea rely on chemosensation throughout
      their life histories including hunting prey, avoiding or deterring predators, in
      the formation of spawning aggregations, synchronizing gamete release and
      targeting appropriate locations for larval settlement. The identities of many of
      the chemical stimuli that mediate these physiological and behavioural processes
      remain unresolved even though evidence indicates they play pivotal roles in the
      functionality of benthic communities. Aspects of chemosensation, as well as
      putative chemically-mediated behaviours and the molecular mechanisms of
      chemoreception, within the Asteroidea are reviewed here, with particular
      reference to the coral reef pest the Crown-of-Thorns starfish Acanthaster planci
      species complex, in the context of mitigation of population outbreaks.

PMID- 29362953
TI  - Chronic coffee consumption and striatal DAT-SPECT findings in Parkinson's
      disease.
AB  - Coffee may interfere with the dopaminergic transmission, and this action would
      possibly enhance motor activity and exert an antidyskinetic effect in Parkinson's
      disease (PD). This study aimed to see whether coffee habit could be associated
      with change in striatal dopamine active transporter (DAT)-single photon emission
      computed tomography (SPECT) imaging in PD. A total of 83 PD patients (71 current
      coffee drinkers and 12 never drinkers) underwent a DAT-SPECT study, using
      [123I]FP-CIT as radionuclide. Socio-demographic and clinical information as well
      as smoking habit was collected at the time of imaging acquisition. The Unified
      Parkinson's Disease Rating Scale part III was used to evaluate disease severity.
      On multivariable analysis, chronic coffee consumption was not associated with any
      significant change in striatal uptake of the radionuclide. However, the number of
      years patients drunk coffee was correlated with a significant increase in age at
      PD onset (p < 0.001). Confirming a previous report, current cigarette smoking was
      associated with a reduction of radionuclide uptake in putamen and caudate (p <
      0.001).

PMID- 29362952
TI  - The role of the clinician in the multi-omics era: are you ready?
AB  - Since Garrod's first description of alkaptonuria in 1902, and newborn screening
      for phenylketonuria introduced in the 1960s, P4 medicine (preventive, predictive,
      personalized, and participatory) has been a reality for the clinician serving
      patients with inherited metabolic diseases. The era of high-throughput
      technologies promises to accelerate its scale dramatically. Genomics,
      transcriptomics, epigenomics, proteomics, glycomics, metabolomics, and lipidomics
      offer an amazing opportunity for holistic investigation and contextual
      pathophysiologic understanding of inherited metabolic diseases for precise
      diagnosis and tailored treatment. While each of the -omics technologies is
      important to systems biology, some are more mature than others. Exome sequencing
      is emerging as a reimbursed test in clinics around the world, and untargeted
      metabolomics has the potential to serve as a single biochemical testing platform.
      The challenge lies in the integration and cautious interpretation of these big
      data, with translation into clinically meaningful information and/or action for
      our patients. A daunting but exciting task for the clinician; we provide clinical
      cases to illustrate the importance of his/her role as the connector between
      physicians, laboratory experts and researchers in the basic, computer, and
      clinical sciences. Open collaborations, data sharing, functional assays, and
      model organisms play a key role in the validation of -omics discoveries. Having
      all the right expertise at the table when discussing the diagnostic approach and
      individualized management plan according to the information yielded by -omics
      investigations (e.g., actionable mutations, novel therapeutic interventions), is
      the stepping stone of P4 medicine. Patient participation and the adjustment of
      the medical team's plan to his/her and the family's wishes most certainly is the
      capstone. Are you ready?

PMID- 29362954
TI  - Profiles of Social and Coping Resources in Families of Children with Autism
      Spectrum Disorder: Relations to Parent and Child Outcomes.
AB  - This study described empirically derived profiles of parents' personal and social
      coping resources in a sample of 207 families of children diagnosed with autism
      spectrum disorder. Latent Profile Analysis identified four family profiles based
      on socieoeconomic risk, coping strategy utilization, family functioning,
      available social supports, and perceptions of family-centered support. During the
      time of children's transition to school, parents in the most disadvantaged group
      experienced the highest levels of parenting stress and depression, and their
      children had significantly lower adaptive behaviour scores and more parent
      reported behavior problems than children in the other three groups. Results
      highlight the need for systematic surveillance of family risk factors so that
      supports can be provided to enhance both parental well-being and children's
      developmental health.

PMID- 29362955
TI  - A Quantitative Analysis of Mental Health Among Sexual and Gender Minority Groups
      in ASD.
AB  - There is increased mental-health adversity among individuals with autism spectrum
      disorder. At the same time, sexual and gender minority groups experience poorer
      mental-health when compared to heteronormative populations. Recent research
      suggests that autistic individuals report increased non-heterosexuality and
      gender-dysphoric traits. The current study aimed to investigate whether as
      membership of minority grouping becomes increasingly narrowed, mental health
      worsened. The present study compared the rates of depression, anxiety, and stress
      using the DASS-21 and Personal Well-Being using the personal well-being index
      between 261 typically-developing individuals and 309 autistic individuals. As
      membership to a minority group became more restrictive, mental health symptoms
      worsened (p < .01), suggesting stressors added. Specialized care is recommended
      for this vulnerable cohort.

PMID- 29362957
TI  - Capsule Commentary on Levine et al., Characteristics and Disparities of Primary
      Care Practices in the United States.

PMID- 29362956
TI  - Adjuvant hormonal therapy for early breast cancer: an epidemiologic study of
      medication adherence.
AB  - PURPOSE: The aim of this study was to determine the prevalence of adherence to
      adjuvant hormonal therapy (AHT) and to identify risk factors for medication non
      adherence in clinical practice in patients with early-stage hormone receptor (HR)
      positive breast cancer (BC) previously treated with chemotherapy. METHODS: We
      carried out a cross-sectional, observational, prospective, and multicenter survey
      based on a structured self-report postal questionnaire (35 items investigating
      six areas). A sample of 474 patients was drawn from 676 patients potentially
      eligible. The structured and validated Morisky Medication Adherence Scale-4 items
      was used for measuring medication adherence. An analysis of risk factors for non
      adherence to AHT was performed using a two-step approach: univariate, then
      multivariate analysis. RESULTS: A total of 280 patients out of the 428 analyzed
      patients participated in the survey, yielding a response rate of 65.4% [60.9
      69.9]. The prevalence of adherence to AHT was estimated at 68.6% [63.1-74.0],
      corresponding to a high level of adherence. Three risk factors for non-adherence
      to AHT were identified: > 2 medications to treat comorbidities (p-value = 0.003),
      age less than 65 years (p-value = 0.008), and patient management in a university
      hospital setting (p-value = 0.014). CONCLUSIONS: Non-adherence is a common,
      complex, and multidimensional healthcare problem. This better understanding and
      knowledge of risk factors will allow healthcare providers (such as oncologists,
      general practitioners, pharmacists) to more easily identify patients at risk for
      non-adherence and help them provide appropriate information about AHT and its
      management, thus improving medication adherence in their patients.

PMID- 29362958
TI  - Supply of Healthcare Providers in Relation to County Socioeconomic and Health
      Status.

PMID- 29362959
TI  - Single-Item Measures for Detecting Sleep Problems in United States Military
      Veterans.
AB  - BACKGROUND: As many as two-thirds of post-9/11 military veterans complain of
      sleep problems, including insomnia-like symptoms. Left untreated, chronic sleep
      problems increase the risk for a range of negative outcomes, including incident
      mental health disorders. However, sleep problems remain overlooked in primary
      care settings. To date, no brief sleep screeners have been developed or
      validated. Items assessing insomnia and poor sleep are often embedded into
      commonly used psychological assessments, and may serve as a viable first step in
      screening. OBJECTIVE: The objective of this study was to examine the utility of
      three single items (i.e., trouble falling asleep, awakening in the early morning,
      and sleep that is restless or disturbed) embedded into the Symptom Checklist-90
      Revised (SCL) for identifying two outcomes of interest, poor sleep and probable
      insomnia. DESIGN: Data were drawn from the cross-sectional Post-Deployment Mental
      Health Study, hosted by the Mid-Atlantic VA Mental Illness Research, Education,
      and Clinical Center. Item performance was evaluated using sensitivity,
      specificity, and predictive value calculations, along with receiver operating
      characteristic (ROC) curves. PARTICIPANTS: Post-9/11 U.S. military veterans with
      one or more overseas deployments and with no current DSM Axis I mental health
      disorder (N = 1118). MAIN MEASURES: An in-person health and sleep questionnaire,
      including the Pittsburgh Sleep Quality Index (PSQI) and the Symptom  Checklist
      (SCL). KEY RESULTS: Using an item response of 1, all three items demonstrated
      moderate sensitivity (0.70-0.78) and acceptable rates of false positives and
      false negatives (0.23-0.48 and 0.11-0.42, respectively) in predicting both
      outcomes, poor sleep and probable insomnia. CONCLUSIONS: Our initial findings
      suggest that existing items in the SCL may serve as a first step in screening for
      sleep problems. Early detection and treatment of sleep problems might prevent or
      ameliorate several negative outcomes, including incident mental health disorders.

PMID- 29362961
TI  - Urantide improves the structure and function of right ventricle as determined by
      echocardiography in monocrotaline-induced pulmonary hypertension rat model.
AB  - Urotensin II (UII) has been reported to play a key role in pulmonary arterial
      hypertension (PAH) development. Doppler echocardiography, a noninvasive and
      simple tool, is recommended for diagnosing PAH. This study was designed to
      investigate the effect of urantide, a UII receptor antagonist, on the structure
      and function of the right ventricle in PAH rat models by Doppler
      echocardiography. A total of 60 male rats were divided into two groups: early-
      and late-treatment groups. Rats in the urantide and MCT (monocrotaline) subgroups
      were injected with 10 MUg/kg urantide in the urantide group or an equal amount of
      normal saline in the MCT group 1 week after PAH model construction in the early
      treatment group and 4 weeks after the construction in the late-treatment group.
      Rats in the control group received an equal volume of normal saline solution. PAH
      related indexes were measured by echocardiography. PAH rat models exhibited
      higher right ventricular diastolic diameter and lower time to peak, ejection
      time, and peak flow velocity of pulmonary artery than controls (P < 0.05).
      However, compared with the MCT group, all abovementioned indexes were improved in
      the urantide group (P < 0.05). No significant differences in pulmonary artery
      diameter and left ventricular ejection fraction were noted among the groups.
      Compared with the MCT group, systolic pulmonary arterial pressure (SPAP) and mean
      pulmonary arterial pressure (mPAP) were significantly lower in the urantide group
      (P < 0.05). SPAP examined by echocardiography was correlated with mPAP by
      catheterization (P < 0.05). Urantide treatment improved right heart failure
      parameters in MCT-induced PAH rats, thus providing a potential new strategy for
      treating PAH.

PMID- 29362960
TI  - Effect of intradialytic exercise on daily physical activity and sleep quality in
      maintenance hemodialysis patients.
AB  - PURPOSE: Physical inactivity and sleep disturbance are frequently observed and
      relate to poor clinical outcomes in maintenance hemodialysis patients. We aimed
      to investigate the effect of intradialytic exercise on daily physical activity
      and sleep quality, measured by an accelerometer, in maintenance hemodialysis
      patients. METHODS: This study randomly assigned ambulatory maintenance
      hemodialysis patients aged >= 20 years on dialysis >= 6 months, without a
      hospitalization history for the previous 3 months to 4 groups: aerobic exercise
      (AE), resistance exercise (RE), combination exercise (CE), and control. A
      stationary bike was used for AE and a TheraBand(r)/theraball for RE. A 12-week
      intradialytic exercise program (3 times/week) was completed in the AE (n = 11),
      RE (n = 10), and CE (n = 12) groups. The control group (n = 13) received only
      warm-up stretching. At baseline and 12-week follow-up, daily physical activity
      and sleep quality were measured with a triaxial accelerometer (wActiSleep-BT;
      ActiGraph, Pensacola, FL) during a continuous 7-day wear period. RESULTS: We
      observed a significant increase in metabolic equivalent (MET; kcal/h/kg) in the
      AE (1.02 +/- 0.03 vs 1.04 +/- 0.04, P = 0.04) and CE (1.06 +/- 0.05 vs 1.09 +/-
      0.08, P = 0.01) groups at 12 weeks compared with baseline. When comparing between
      group changes in MET, there was a significant increase in METs in the CE group
      (0.03 +/- 0.03 vs - 0.01 +/- 0.04, P = 0.02) compared with the control group. The
      total number of sedentary bouts (per week) decreased significantly in the AE (200
      +/- 37 vs 174 +/- 36, P = 0.01), RE (180 +/- 31 vs 130 +/- 49, P = 0.03), and CE
      groups (180 +/- 45 vs 152 +/- 46, P = 0.04) at 12 weeks compared with baseline.
      The average sleep fragmentation index, indicating poor sleep quality, decreased
      significantly at 12 weeks compared with baseline in the AE (51.4 +/- 8.0 vs 44.5
      +/- 9.6, P = 0.03) and RE groups (52.3 +/- 7.3 vs 40.0 +/- 15.4, P = 0.01).
      CONCLUSIONS: Intradialytic exercise appears to be clinically beneficial in
      improving daily physical activity and sleep quality in maintenance hemodialysis
      patients.

PMID- 29362962
TI  - Tocilizumab reduces complement C3 and C4 serum levels in rheumatoid arthritis
      patients.
AB  - Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, is known to be
      able to rapidly reduce acute phase reactants. Although complement components are
      part of the acute phase, no data are available on a possible effect of
      tocilizumab on complement proteins. Serum levels of complement components C3 and
      C4 were retrospectively assessed in 19 consecutive rheumatoid arthritis patients
      eligible for tocilizumab treatment. Tocilizumab was found to reduce all known
      acute phase reactants, including C3 and C4 levels. C3 and C4 were found to
      decrease as early as 4 weeks after the first tocilizumab infusion. On average, C3
      decreased by 24.02, 27.35, 33.62, and 32.81%, as compared to pre-treatment
      values, after 1, 3, 6, and 12 months of therapy, respectively; likewise, C4
      decreased by 44.74, 43.40, 54.33, and 54.56% at the same time points with respect
      to pre-treatment values. A discrete proportion of patients (38.46 and 30.76% for
      C3 and C4, respectively) displayed subnormal complement serum levels early (4
      weeks) after initiation of tocilizumab treatment, which raised suspicion for
      complement consumption. However, no circulating immunocomplexes were found nor
      did any patient ever display clinical features of immunocomplex disease during a
      median follow-up of 38 months. After 12 months of therapy, 68.75 and 56.25% of
      patients had abnormally low C3 and C4 serum levels, respectively. Reduction in C3
      and C4 serum levels should be included among the anti-inflammatory effects
      exerted by tocilizumab and are thus to be considered as an expected outcome of
      the mechanism of action of this drug.

PMID- 29362963
TI  - Prognostic Value of Exon 19 Versus 21 EGFR Mutations Varies According to Disease
      Stage in Surgically Resected Non-small Cell Lung Cancer Adenocarcinoma.
AB  - BACKGROUND: The prognostic value of exon 19 and 21 EGFR mutations in stage IV non
      small cell lung cancer (NSCLC) is well established. OBJECTIVE: We aimed to
      evaluate the prognostic value of the mutations in surgically resected NSCLC.
      METHODS: We retrospectively reviewed data from 1798 surgically resected NSCLC
      adenocarcinomas between 2007 and 2017 in three departments of thoracic surgery
      (Nancy/Strasbourg, France, and Torino, Italy) for whom mutational status was
      known. Overall survival (OS) was evaluated using log-rank and Cox proportional
      hazard models. RESULTS: EGFR exon 19 deletion was observed in 108 patients
      (55.1%) and exon 21 L858R mutations were observed in 88 patients (44.9%). In
      stage I, the median OS was not significantly different between exons 19 and 21 (p
      = 0.54), while, in stage II, the median OS reached 65 months [95% confidence
      interval (CI) 41.67-88.33] for exon 19 mutations and decreased to 48 months for
      exon 21 mutations (95% CI 44.21-51.79; p = 0.027). In multivariate analysis, exon
      19 deletion remained a favorable prognostic factor [hazard ratio (HR) 0.314, 95%
      CI 0.098-0.997; p = 0.05]. In stage III, the median OS reached 66 months (95% CI
      44.67-87.32) for exon 19 mutations and decreased to 32 months for exon 21
      mutations (95% CI 29.86-34.14; p = 0.03). In multivariate analysis, exon 19
      deletion remained a significantly favorable prognostic factor (HR 0.165, 95% CI
      0.027-0.999; p = 0.05). CONCLUSION: The prognostic value of EGFR exon 19 and 21
      mutations appears to be different according to disease stage in surgically
      resected NSCLC.

PMID- 29362964
TI  - Pathogen Transmission from Humans to Great Apes is a Growing Threat to Primate
      Conservation.
AB  - All six great ape species are listed as endangered or critically endangered by
      the IUCN and experiencing decreasing population trends. One of the threats to
      these non-human primates is the transmission of pathogens from humans. We
      conducted a literature review on occurrences of pathogen transmission from humans
      to great apes to highlight this often underappreciated issue. In total, we found
      33 individual occurrences of probable or confirmed pathogen transmission from
      humans to great apes: 23 involved both pathogen and disease transmission, 7
      pathogen transmission only, 2 positive antibody titers to zoonotic pathogens, and
      1 pathogen transmission with probable disease. Great ape populations were
      categorized into captive, semi-free-living, and free-living conditions. The
      majority of occurrences involved chimpanzees (Pan troglodytes) (n = 23) or
      mountain gorillas (Gorilla beringei beringei) (n = 8). These findings have
      implications for conservation efforts and management of endangered great ape
      populations. Future efforts should focus on monitoring and addressing zoonotic
      pathogen and disease transmission between humans, great ape species, and other
      taxa to ensure the health of humans, wild and domestic animals, and the
      ecosystems we share.

PMID- 29362965
TI  - Using a Harm Reduction Approach in an Environmental Case Study of Fish and
      Wildlife Health.

PMID- 29362966
TI  - Fusion imaging with contrast-enhanced ultrasonography for evaluating the early
      therapeutic efficacy of radiofrequency ablation for small hypervascular
      hepatocellular carcinomas with iso-echoic or unclear margins on conventional
      ultrasonography.
AB  - PURPOSE: We evaluated the efficacy of fusion imaging combining contrast-enhanced
      ultrasonography (CEUS) images and arterial phase contrast-enhanced CT (CECT) or
      hepatobiliary phase magnetic resonance imaging with gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (EOB-MRI) images for the early evaluation of
      the effectiveness of radiofrequency ablation (RFA) for small hypervascular
      hepatocellular carcinoma (HCC) with iso-echoic or unclear margins on conventional
      US. METHODS: Forty HCCs (22 iso-echoic and 18 unclear margin lesions) with mean
      diameters of 13.7 mm were treated using RFA under the guidance of fusion imaging
      with CEUS. The adequacy of RFA was evaluated using fusion imaging with CEUS 1 day
      after RFA. CECT or EOB-MRI was performed 1 month after RFA. We reviewed the
      images obtained using both modalities. RESULTS: When the 1-month CECT or EOB-MRI
      scans were used as the reference standard, the sensitivity, specificity, and
      accuracy of the 1-day fusion imaging for the diagnosis of the adequate ablation
      of these HCCs were 97, 100, and 98%, respectively; the kappa value for the
      agreement between the findings using the two modalities was 0.655. CONCLUSION:
      Fusion imaging with CEUS appears to be a useful method for the early evaluation
      of the efficacy of RFA for the treatment of HCCs with iso-echoic or unclear
      margins on conventional US.

PMID- 29362967
TI  - Does severe obstructive sleep apnea syndrome alter retrobulbar blood flow? A
      color Doppler ultrasound study.
AB  - PURPOSE: To evaluate extraocular orbital vessels with color Doppler ultrasound
      (CDU) and investigate the effects of severe obstructive sleep apnea (OSA) on
      retrobulbar blood flow. METHODS: Between February 2014 and September 2015, 30
      patients with severe OSA (apnea-hypopnea index (AHI) > 30) and 28 controls were
      prospectively included in this study. Intraocular pressure (IOP) was measured
      with a Goldmann applanation tonometer, and CDU was used to evaluate the
      retrobulbar vessels. RESULTS: The mean AHI score for the OSA group was 63.2 +/-
      21.5 per hour. The IOP values were significantly higher in the severe OSA group
      (p < 0.05). The central retinal artery peak systolic velocity (PSV) (p < 0.05)
      and end-diastolic velocity (EDV) (p < 0.02), and the ophthalmic artery (OA) PSV
      and EDV, were found to be significantly lower in the OSA group (p < 0.05).
      CONCLUSION: Severe OSA causes an increase in IOP and a decrease in flow velocity
      in the retrobulbar circulation.

PMID- 29362968
TI  - Bilateral Versus Single Internal Thoracic Artery Grafts.
AB  - PURPOSE OF REVIEW: Several advances have been made in recent years to improve
      outcome for patients with coronary artery disease. One of the most debated topics
      regarding surgical treatment with coronary artery bypass grafting (CABG) is graft
      selection. This review aims to present the current status and scientific evidence
      for bilateral internal thoracic artery (BITA) grafting. RECENT FINDINGS:
      Observational studies and pooled analyses suggest that BITA grafting is
      associated with improved survival. Early results from a large randomized
      controlled trial report safety and efficacy of the method. The improved survival
      might be amplified in select groups, but with an increase in sternal wound
      related complications. The benefit of BITA grafts seems to remain to an
      approximate age of 69 years at surgery. CABG with BITA grafts is likely
      associated with improved long-term survival at a cost of an increase in sternal
      wound infections. Ten-year results from the Arterial Revascularization Trial are
      expected in 2018, providing the best evidence regarding the method yet. Early
      results show it is a safe method in most patient categories considerable for
      CABG.

PMID- 29362969
TI  - "What Goes Around Comes Around": Attitudes and Practices Regarding Ageing and
      Care for the Elderly Among Moroccan Muslim Women Living in Antwerp (Belgium).
AB  - The aim of this article is threefold. First, we seek to elicit the attitudes and
      practices of middle-aged and elderly Moroccan Muslim women towards ageing and
      care for the elderly. Second, we aim to identify possible differences between
      middle-aged and elderly women's attitudes and practices. Third, we seek to
      explore which role religion plays in their attitudes and practices. Qualitative
      empirical research was conducted with a sample of middle-aged and elderly
      Moroccan Muslim women living in Antwerp (Belgium) (n = 30) and with experts in
      the field (n = 15). Our study unveils that ageing and care for the elderly are
      clearly understood from a religious framework. More specifically, theological and
      eschatological considerations take up a central position. Access to and
      utilization of professional elderly care is hampered by several barriers (e.g.
      religious, cultural and financial). We found a more open attitude towards
      professional elderly care among middle-aged women than among elderly women.

PMID- 29362971
TI  - Engineering co-culture system for production of apigetrin in Escherichia coli.
AB  - Microbial cells have extensively been utilized to produce value-added bioactive
      compounds. Based on advancement in protein engineering, DNA recombinant
      technology, genome engineering, and metabolic remodeling, the microbes can be re
      engineered to produce industrially and medicinally important platform chemicals.
      The emergence of co-culture system which reduces the metabolic burden and allows
      parallel optimization of the engineered pathway in a modular fashion restricting
      the formation of undesired byproducts has become an alternative way to synthesize
      and produce bioactive compounds. In this study, we present genetically engineered
      E. coli-based co-culture system to the de novo synthesis of apigetrin (APG), an
      apigenin-7-O-beta-D-glucopyranoside of apigenin. The culture system consists of
      an upstream module including 4-coumarate: CoA ligase (4CL), chalcone synthase,
      chalcone flavanone isomerase (CHS, CHI), and flavone synthase I (FNSI) to
      synthesize apigenin (API) from p-coumaric acid (PCA). Whereas, the downstream
      system contains a metabolizing module to enhance the production of UDP-glucose
      and expression of glycosyltransferase (PaGT3) to convert API into APG. To
      accomplish this improvement in titer, the initial inoculum ratio of strains for
      making the co-culture system, temperature, and media component was optimized.
      Following large-scale production, a yield of 38.5 uM (16.6 mg/L) of APG was
      achieved. In overall, this study provided an efficient tool to synthesize
      bioactive compounds in microbial cells.

PMID- 29362970
TI  - Lipopolysaccharide-Induced Striatal Nitrosative Stress and Impaired Social
      Recognition Memory Are Not Magnified by Paraquat Coexposure.
AB  - Systemic inflammation triggered by lipopolysaccharide (LPS) administration
      disrupts blood-brain barrier (BBB) homeostasis in animal models. This event leads
      to increased susceptibility of several encephalic structures to potential
      neurotoxicants present in the bloodstream. In this study, we investigated the
      effects of alternate intraperitoneal injections of LPS on BBB permeability,
      social recognition memory and biochemical parameters in the striatum 24 h and 60
      days after treatments. In addition, we investigated whether the exposure to a
      moderate neurotoxic dose of the herbicide paraquat could potentiate LPS-induced
      neurotoxicity. LPS administration caused a transient disruption of BBB integrity,
      evidenced by increased levels of exogenously administered sodium fluorescein in
      the striatum. Also, LPS exposure caused delayed impairment in social recognition
      memory (evaluated at day 38 after treatments) and increase in the striatal levels
      of 3-nitrotyrosine. These events were observed in the absence of significant
      changes in motor coordination and in the levels of tyrosine hydroxylase (TH) in
      the striatum and substantia nigra. PQ exposure, which caused a long-lasting
      decrease of striatal mitochondrial complex I activity, did not modify LPS-induced
      behavioral and striatal biochemical changes. The results indicate that systemic
      administration of LPS causes delayed social recognition memory deficit and
      striatal nitrosative stress in adult mice and that the coexposure to a moderately
      toxic dose of PQ did not magnify these events. In addition, PQ-induced inhibition
      of striatal mitochondrial complex I was also not magnified by LPS exposure,
      indicating the absence of synergic neurotoxic effects of LPS and PQ in this
      experimental model.

PMID- 29362973
TI  - Role of topical interferon alpha-2b in 'mitomycin-C-resistant' ocular surface
      squamous neoplasia: our preliminary findings.
AB  - PURPOSE: To report the clinical presentation of mitomycin-C (MMC)-resistant
      ocular surface squamous neoplasia (OSSN) and its treatment outcome with topical
      interferon alpha-2b (IFNalpha-2b). METHODS: A prospective, non-randomised, pilot
      study enrolling clinically diagnosed OSSN patients. The inclusion criterion was
      resistance of OSSN to standard topical MMC (0.02%) chemotherapy. The resistance
      was defined as 'no clinical response' in the terms of reduction in tumour size,
      extension and vascularity after minimum 6 weeks 'on-cycles' of MMC. Any previous
      surgical intervention or recurrent OSSN lesions were excluded. Topical MMC was
      stopped in all, and topical IFNalpha-2b (1million IU/ml) eyedrops were prescribed
      to each patient. At first presentation, the clinical features and side-effect
      profile of MMC was noted and therapeutic effect of IFNalpha-2b was clinically
      monitored at each follow-up. Topical immunotherapy was continued for 24 weeks and
      a minimum follow-up of 12 weeks was observed after stopping IFNalpha-2b. RESULTS:
      Six patients with a mean age of 62 years met the inclusion criteria. At
      presentation, all had unilateral, circumscribed, sessile and unifocal lesions
      with mean dimensions of 7.67 * 5.17 mm. Four patients had temporal lesions while
      surface keratin, pigmentation and corneal involvement were noted in three
      lesions, separately. All lesions had dilated and tortuous feeder vessels. All six
      tumours resolved completely over a mean tumour resolution time of 16 weeks while
      the total duration of IFNalpha-2b treatment was 24 weeks. After stopping
      immunotherapy, a mean of 14.5 weeks follow-up was observed. None showed any
      recurrence. The approximate cost of total therapy session was 8400 Indian rupees.
      CONCLUSION: The OSSN lesions showing 'less or no response' to topical MMC may be
      shifted to topical recombinant IFNalpha-2b before proceeding for a surgical
      excision.

PMID- 29362972
TI  - Advancing biotechnology with CRISPR/Cas9: recent applications and patent
      landscape.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) is poised to
      become one of the key scientific discoveries of the twenty-first century.
      Originating from prokaryotic and archaeal immune systems to counter phage
      invasions, CRISPR-based applications have been tailored for manipulating a broad
      range of living organisms. From the different elucidated types of CRISPR
      mechanisms, the type II system adapted from Streptococcus pyogenes has been the
      most exploited as a tool for genome engineering and gene regulation. In this
      review, we describe the different applications of CRISPR/Cas9 technology in the
      industrial biotechnology field. Next, we detail the current status of the patent
      landscape, highlighting its exploitation through different companies, and
      conclude with future perspectives of this technology.

PMID- 29362974
TI  - Mapping Brain Activity with Electrocorticography: Resolution Properties and
      Robustness of Inverse Solutions.
AB  - Electrocorticography (ECoG) is an electrophysiological technique that records
      brain activity directly from the cortical surface with high temporal (ms) and
      spatial (mm) resolution. Its major limitations are in the high invasiveness and
      in the restricted field-of-view of the electrode grid, which partially covers the
      cortex. To infer brain activity at locations different from just below the
      electrodes, it is necessary to solve the electromagnetic inverse problem.
      Limitations in the performance of source reconstruction algorithms from ECoG have
      been, to date, only partially addressed in the literature, and a systematic
      evaluation is still lacking. The main goal of this study is to provide a
      quantitative evaluation of resolution properties of widely used inverse methods
      (eLORETA and MNE) for various ECoG grid sizes, in terms of localization error,
      spatial dispersion, and overall amplitude. Additionally, this study aims at
      evaluating how the use of simultaneous electroencephalography (EEG) affects the
      above properties. For these purposes, we take advantage of a unique dataset in
      which a monkey underwent a simultaneous recording with a 128 channel ECoG grid
      and an 18 channel EEG grid. Our results show that, in general conditions, the
      reconstruction of cortical activity located more than 1 cm away from the ECoG
      grid is not accurate, since the localization error increases linearly with the
      distance from the electrodes. This problem can be partially overcome by recording
      simultaneously ECoG and EEG. However, this analysis enlightens the necessity to
      design inverse algorithms specifically targeted at taking into account the
      limited field-of-view of the ECoG grid.

PMID- 29362975
TI  - "Clothesline technique" for proximal tibial shaft fracture fixation using
      conventional intramedullary nail: a simple, useful, and inexpensive technique to
      prevent fracture malalignment.
AB  - Treatment of proximal tibial shaft fractures is always challenging. Despite the
      development of modern techniques, the literature still shows high complication
      rates, especially regarding proximal fragment malalignment. It is well known that
      knee position in flexion during tibial nailing is responsible for extension and
      valgus deformities of the proximal fragment. Unlike in tibial shaft fractures,
      nails do not reduce proximal tibial fractures due to the medullary canal width.
      This study aims to describe a simple, useful, and inexpensive technique to
      prevent valgus and extension deformities when treating proximal tibial fractures
      using conventional nails: the so-called clothesline technique.

PMID- 29362977
TI  - RETRACTED ARTICLE: Biceps tendon interposition in two-part fracture of the
      humeral surgical neck.

PMID- 29362978
TI  - Social tolerance in not-so-social pumas.
AB  - Elbroch, Levy, Lubell, Quigley, and Caragiulo (2017, Science Advances, 3,
      e170218) used GPS and motion-activated camera technology to track and rate the
      interactions between solitary wild pumas. They found that tolerance at feeding
      sites was not predicted by kinship but, rather, indicated the ability to engage
      in direct reciprocity, challenging previous assumptions about social cognition in
      solitary species.

PMID- 29362976
TI  - The ABC and pain in trauma.
AB  - Musculoskeletal trauma in the emergency setting is a challenge for orthopaedic
      surgeons. Life- and limb-threatening injuries of the extremities should be
      treated as soon as possible, since major musculoskeletal trauma can be the cause
      of significant bleeding. However, musculoskeletal trauma is often related to
      thoracic trauma. Management of the former should be performed only after
      patient's airway is maintained and breathing is secured with appropriate pain
      monitoring and management by expert anesthesiologists. This article discusses the
      association of musculoskeletal with thoracic trauma care and emphasizes on pain
      as a vital sign in trauma.

PMID- 29362979
TI  - Guideline from Japanese Society of Echocardiography: 2018 focused update
      incorporated into Guidance for the Management and Maintenance of Echocardiography
      Equipment.
AB  - Echocardiography plays a pivotal role as an imaging modality in the modern
      cardiology practice. Information derived from echocardiography is definitely
      helpful for a patient care. The Japanese Society of Echocardiography has promoted
      echocardiography for a routine clinical and research use. One of the missions of
      the Society is to provide information that is useful for high-quality
      examinations. To ensure it, we believe equipment in good conditions and a
      comfortable environment are important for both a patient and an examiner. Thus,
      the Committee for Guideline Writing, the Japanese Society of Echocardiography
      published brief guidance for the routine use of echocardiography equipment in
      2015. Recently, the importance of international standardization has been
      emphasized in the medical laboratories. Accordingly, the committee has revised
      and updated our guidance for the routine use of echocardiography equipment.

PMID- 29362980
TI  - Efficacy and safety of switching to nilotinib in patients with CML-CP in major
      molecular response to imatinib: results of a multicenter phase II trial (NILSw
      trial).
AB  - We evaluated the efficacy and safety of switching to nilotinib in CML-CP patients
      who had achieved MMR with continuous detectable BCR-ABL1 transcript levels after
      long-term imatinib treatment. Patients who had achieved MMR, but not deep
      molecular response (DMR), after > 18 months from the initiation of imatinib
      received nilotinib 400 mg twice daily for up to 24 months. BCR-ABL1 transcript
      levels were assessed every 3 months. Thirty-eight patients with a median age of
      57.5 years (range 22-76 years) were evaluated. Twenty-seven patients completed 24
      months of nilotinib treatment; 11 discontinued nilotinib due to retraction of
      consent (three patients), loss of MMR (1), intolerance (3) or AEs (5). Twenty
      patients [52.6%, (90% CI 38.2-66.7%)] achieved DMR. The cumulative incidence of
      achieving DMR by the time of 3, 6, 9, 12, 15, 18, and 21 months was 22.9, 37.7,
      47.0, 53.7, 53.7, 53.7, and 53.7%, respectively. Adverse events were consistent
      with those reported in other nilotinib studies. Patients experienced each of the
      following cardiovascular complications: atrial fibrillation (G2), chest tightness
      and dyspnea (G1), myocardial infarction (G2) and heart failure (G3) (n = 1 for
      each complication). This study indicates nilotinib achieves strong, rapid
      induction of DMR for patients who achieved MMR after long-term imatinib therapy.

PMID- 29362981
TI  - Interventions at the Transition from Prison to the Community for Prisoners with
      Mental Illness: A Systematic Review.
AB  - Prisoners have high rates of mental illness and the transition from prison to the
      community is a problematic time for the provision of mental health services and a
      range of negative outcomes have been identified in this period. A systematic
      review was conducted to identify interventions for prisoners with diagnosed
      mental health conditions that targeted this transition period. Fourteen papers
      from 13 research studies were included. The interventions identified in this
      review were targeted at different stages of release from prison and their content
      differed, ranging from Medicaid enrolment schemes to assertive community
      treatment. It was found that insurance coverage, and contact with mental health
      and other services can be improved by interventions in this period but the impact
      on reoffending and reincarceration is complex and interventions may lead to
      increased return to prison. There is a developing evidence base that suggests
      targeting this period can improve contact with community mental health and other
      health services but further high quality evidence with comparable outcomes is
      needed to provide more definitive conclusions. The impact of programmes on return
      to prison should be evaluated further to establish the effect of interventions on
      clinical outcomes and to clarify the role of interventions on reincarceration.

PMID- 29362982
TI  - Multi-modality imaging: Bird's eye view from the 2017 American Heart Association
      Scientific Sessions.
AB  - This review summarizes key imaging studies that were presented in the American
      Heart Association Scientific Sessions 2017 related to the fields of nuclear
      cardiology, cardiac computed tomography, cardiac magnetic resonance, and
      echocardiography. The aim of this bird's eye view is to inform readers about
      multiple studies reported at the meeting from these different imaging modalities.
      While such a review is most useful for those that did not attend the conference,
      we find that a general overview may also be useful to those that did since it is
      often difficult to get exposure to many abstracts at large meetings. The review,
      therefore, aims to help readers stay updated on the newest imaging studies
      presented at the meeting and will hopefully stimulate new ideas for future
      research in imaging.

PMID- 29362983
TI  - Detrimental effects of nitroglycerin use during regadenoson vasodilator stress
      testing: A cautionary tale.
AB  - Vasodilator agents such as adenosine and regadenoson are commonly used
      pharmacologic stressors to assess for ischemia in patients undergoing myocardial
      perfusion studies. The recommended reversal agent for this mode of stress is
      aminophylline, although nitroglycerin is commonly administered as an attempt to
      reverse the symptoms or electrocardiographic (EKG) changes during the stress
      test. We demonstrate through two cases that incorrect administration of
      nitroglycerin can induce hypotension and worsen coronary steal, whereas
      appropriate administration of aminophylline can reverse the effects of
      pharmacologic vasodilators. While nitroglycerin is often used in patients with
      organic angina, it has the potential to worsen ischemia in the setting of
      pharmacologic vasodilator administration. These cases underscore the importance
      of administering the correct reversal agent for pharmacologic stress tests.

PMID- 29362984
TI  - Clinical significance of hWAPL polymorphisms in the risk of cervical
      carcinogenesis.
AB  - To investigate the clinical significance of human wings apart-like (hWAPL)
      genetic polymorphisms in cervical carcinogenesis. hWAPL polymorphisms and human
      papillomavirus (HPV) types were examined in 175 cervical smears of exfoliated
      cervical cell samples using a real-time polymerase chain reaction system. A
      significant difference was detected in the frequency of the CC genotype between
      the HPV(+) low-grade squamous intraepithelial lesion (LSIL) and high-grade
      squamous intraepithelial lesion (HSIL) groups [Odds ratio 0.21, 95% confidence
      interval (CI) 0.0723-0.61; P = 0.0029]. A significant difference was noted in the
      frequency of the CC genotype between the high-risk HPV-positive LSIL and HSIL
      groups (odds ratio 0.2955, 95% CI 0.0893-0.9771; P = 0.0414). The CC genotype of
      hWAPL gene promoter polymorphism may be associated with cervical carcinogenesis.

PMID- 29362985
TI  - Opium Consumption and the Incidence of Cancer: Does Opium Account as an Emerging
      Risk Factor for Gastrointestinal Cancer?
AB  - PURPOSE: Some epidemiological studies have shown an association between opium
      consumption and the incidence of gastrointestinal (GI) cancer. The present study
      was designed to investigate the effects of opium on the initiation of GI cancer
      in rats. METHODS: Forty-five rats were randomly divided into three groups; each
      received different treatment for 40 weeks. The rats in group 1 received purified
      water, while animals in group 2 were treated with 5 mg/kg diethylnitrosamine
      (DEN) orally for 8 weeks and continued with purified water by the end of the
      experiment. The third experimental group received 300 mg/kg opium for 16 weeks
      and then continued with 50 mg/kg phenobarbital by the end of the 40th week. The
      growth of tumors in the treated groups was assessed by histological changes and
      the up/down expression of p53, cdkn1, cdk2, e-cdh, and n-cdh genes in different
      parts of GI tract. RESULTS: Histological examinations revealed that DEN was able
      to induce the growth of tumor in GI tract as shown by active mitotic figure in
      different regions of GI system and hyperplasia of hepatocytes associated with
      infiltration of inflammatory cells, intestinal villous hypertrophy, and
      colorectal adenoma. There was also significant (p < 0.05) overexpression of p53,
      cdk2, and n-Cdh genes in different parts of digestive system in DEN-treated
      group. However, these pathological changes and the degradation of gene expression
      were not observed in the opium-treated group. CONCLUSION: The results of this
      study suggest that the opium does not promote the initiation of cancer in GI
      tract.

PMID- 29362986
TI  - Transcutaneous electromyographic respiratory muscle recordings to quantify
      patient-ventilator interaction in mechanically ventilated children.
AB  - BACKGROUND: To explore the feasibility of transcutaneous electromyographic
      respiratory muscle recordings to automatically quantify the synchronicity of
      patient-ventilator interaction in the pediatric intensive care unit. METHODS:
      Prospective observational study in a tertiary paediatric intensive care unit in
      an university hospital. Spontaneous breathing mechanically ventilated children <
      18 years of age were eligible for inclusion. Patients underwent a 5-min
      continuous recording of ventilator pressure waveforms and transcutaneous
      electromyographic signal of the diaphragm. To evaluate patient-ventilator
      interaction, the obtained neural inspiration and ventilator pressurization
      timings were used to calculate trigger and cycle-off errors of each breath.
      Calculated errors were displayed in the dEMG-phase scale. RESULTS: Data of 23
      patients were used for analysis. Based on the dEMG-phase scale, the median rates
      of synchronous, dyssynchronous and asynchronous breaths as classified by the
      automated analysis were 12.2% (1.9-33.8), 47.5% (36.3-63.1), and 28.9% (6.6
      49.0). CONCLUSIONS: The dEMG-phase scale quantifying patient-ventilator breath
      synchronicity was demonstrated to be feasible and a reliable scale for
      mechanically ventilated children, reflected by high intra-class correlation
      coefficients. As this non-invasive tool is not restricted to a type of
      ventilator, it could easily be clinical implemented in the ventilated pediatric
      population. However; correlation studies between the EMG signal measured by
      surface EMG and esophageal catheters have to be performed.

PMID- 29362987
TI  - Geant4 beam model for boron neutron capture therapy: investigation of neutron
      dose components.
AB  - Boron neutron capture therapy (BNCT) is a biochemically-targeted type of
      radiotherapy, selectively delivering localized dose to tumour cells diffused in
      normal tissue, while minimizing normal tissue toxicity. BNCT is based on thermal
      neutron capture by stable [Formula: see text]B nuclei resulting in emission of
      short-ranged alpha particles and recoil [Formula: see text]Li nuclei. The purpose
      of the current work was to develop and validate a Monte Carlo BNCT beam model and
      to investigate contribution of individual dose components resulting of neutron
      interactions. A neutron beam model was developed in Geant4 and validated against
      published data. The neutron beam spectrum, obtained from literature for a
      cyclotron-produced beam, was irradiated to a water phantom with boron
      concentrations of 100 MUg/g. The calculated percentage depth dose curves (PDDs)
      in the phantom were compared with published data to validate the beam model in
      terms of total and boron depth dose deposition. Subsequently, two sensitivity
      studies were conducted to quantify the impact of: (1) neutron beam spectrum, and
      (2) various boron concentrations on the boron dose component. Good agreement was
      achieved between the calculated and measured neutron beam PDDs (within 1%). The
      resulting boron depth dose deposition was also in agreement with measured data.
      The sensitivity study of several boron concentrations showed that the calculated
      boron dose gradually converged beyond 100 MUg/g boron concentration. This results
      suggest that 100MUg/g tumour boron concentration may be optimal and above this
      value limited increase in boron dose is expected for a given neutron flux.

PMID- 29362988
TI  - A Comparative Study on Immobilization of Fructosyltransferase in Biodegradable
      Polymers by Electrospinning.
AB  - Commercial application of biocatalysts depends on the efficiency of the
      immobilization method and residual enzyme activity. Electrospinning offers a
      simple and versatile route to immobilize enzymes in submicron-sized fibers and
      thus improved mass transfer characteristics. Performance of encapsulation of
      fructosyltransferase from Bacillus subtilis by emulsion, suspension, and coaxial
      electrospinning was compared. We particularly focused on the effect of
      hydrophilic properties of a set of biodegradable polymers on support's activity.
      Bioactivity of electrospun support in aqueous medium increased in order of the
      matrix hydrophilicity. Additionally, the efficiency of electrospun fibers was
      compared with Sepabeads(r), commercial epoxy-activated resins. In fibers, enzyme
      loading of 68.1 mg/g and specific enzyme activity of 5.5 U/mg was achieved
      compared to 49.5 mg/g and 2.2 U/mg on Sepabeads. Fructosyltransferase exhibited
      high sensitivity towards organic solvents and covalent attachment, respectively.
      Immobilization of native enzyme in coaxial fibers increased the specific activity
      to approx. 30 U/mg which corresponds to 24% of that of the free enzyme. Finally,
      operational stability of fiber supports was examined in a plug-flow reactor and
      5% of initial substrate conversion remained after > 2000 cycles. The efficiency
      of core-shell immobilizates compared to one-dimensional fibers was both in batch
      and continuous reaction at least 4.4-fold higher.

PMID- 29362990
TI  - Characterization and Antibacterial Activity Against Helicobacter pylori of Lactic
      Acid Bacteria Isolated from Thai Fermented Rice Noodle.
AB  - A total of 32 lactic acid bacteria (LAB) were isolated from Khanom-jeen, a Thai
      traditional fermented rice noodle. They belonged to the genus Leuconostoc (Ln),
      Lactobacillus (Lb), Enterococcus (E), Lactococcus (Lc), and Weissella (W), based
      on their phenotypic characteristics and 16S rRNA gene sequence analyses. The
      strains were identified as Ln. pseudomesenteroides (group 1, two strains), Ln.
      citreum (group 2, three strains), Ln. lactis (group 3, three strains), Lb.
      paracasei subsp. tolerans (group 4, two strains), E. faecium (group 5, three
      strains), Lc. lactis subsp. lactis (group 6, one strain), W. confusa (group 7,
      six strains), Lb. fermentum (group 8, seven strains), and Lb. plantarum subsp.
      plantarum and Lb. pentosus (group 9, five strains). Fifteen strains exhibited the
      inhibitory activity against Helicobacter pylori clinical isolates by spot-on-lawn
      method. Lb. fermentum P43-01 resisted to bile acids showed the broad spectrum of
      antimicrobial activity against H. pylori strains MS83 and BK364. These
      antagonistic effects were associated with proteinaceous compounds which are
      sensitive to alpha-chymotrypsin and pepsin. Results indicated that production of
      bacteriocin-like substances of selected strain might be the significant mechanism
      that exerted the inhibition on H. pylori. A potential strain could be used as
      probiotics in alternative or adjunctive therapy for a patient suffering from H.
      pylori infection.

PMID- 29362989
TI  - Radiolabeled GX1 Peptide for Tumor Angiogenesis Imaging.
AB  - Early and accurate detection of primary or metastatic tumors is of great value in
      staging, treatment management, and prognosis. Tumor angiogenesis plays an
      essential role in the growth, invasion, and metastatic spread of solid cancers,
      and so, is a promising approach for tumor imaging. The GX1 (CGNSNPKSC) peptide
      was identified by phage display library and has been investigated as a marker for
      human cancers. This study aims to evaluate the 99mTc-HYNIC-PEG4-c (GX1) as a
      biomarker for tumor imaging. Our results showed that GX1 specifically binds to
      tumor cells in vitro. SKMEL28 and MDA-MB231 cells achieved total binding peak at
      60 min of incubation. For B16F10 and MKN45 cells, the total and specific binding
      were similar during all time points, while A549 cell line showed rapid cellular
      total uptake of the tracer at 30 min of incubation. Biodistribution showed low
      non-specific uptakes and rapid renal excretion. Melanoma tumors showed enhanced
      GX1 uptake in animal model at 60 min, and it was significantly blocked by cold
      peptide. The radiotracer showed tumor specificity, especially in melanomas that
      are highly vascularized tumors. In this sense, it should be considered in future
      studies, aiming to evaluate degree of angiogenesis, progression, and invasion of
      tumors.

PMID- 29362991
TI  - Reduced spontaneous low frequency oscillations as measured with functional near
      infrared spectroscopy in mild cognitive impairment.
AB  - Spontaneous low frequency oscillations (LFO) in functional imaging data have
      gained increased interest in the study of cognitive decline. Persons diagnosed
      with mild cognitive impairment (MCI) and Alzheimer's disease (AD) display
      alterations in their amount of LFO in various brain regions. This is commonly
      interpreted as disruptions in the autoregulation of the cerebral microvascular
      system. In the present study LFO (0,07-0,11 Hz) were measured with 52-channel
      near-infrared spectroscopy (NIRS) in 61 healthy elderly persons (70-76 years), 54
      MCI subjects (70-76 years) and 25 healthy young controls (21-48 years) during
      rest over the frontal and the parietal cortex. Both MCI and healthy elderly
      controls showed less LFO in the frontal cortex as compared to young subjects. For
      the parietal cortex a decrease in LFO could be observed for the MCI group in
      comparison to healthy elderly subjects. Correlations of more LFO with worse
      performance in neuropsychological tests point to compensatory processes. LFO
      measured with NIRS might be especially suited for longitudinal studies aiming at
      predicting cognitive decline.

PMID- 29362992
TI  - White matter integrity correlates with residual consciousness in patients with
      severe brain injury.
AB  - Previous studies have suggested that white matter disruption plays an important
      role in disorders of consciousness (DOC) after severe brain injury. Nevertheless,
      the integrity of white matter architecture supporting consciousness and its
      relations with clinical severity in patients with DOC remain to be established.
      In this study, diffusion tensor imaging (DTI) data was collected from 14 DOC
      patients and 15 healthy control subjects. We combined tract-based spatial
      statistics (TBSS) with region of interest (ROI) analysis to examine differences
      of DTI metrics on white matter skeletons between DOC patients and healthy
      controls, and the association between white matter integrity and patients'
      residual consciousness assessed by Coma Recovery Scale-Revised (CRS-R). We found
      that: (1) patients with DOC had widespread white matter integrity disruptions,
      especially in the fornix; (2) the alteration of white matter microstructure was
      mainly attributed to the increase in radial diffusivity, possibly reflecting
      demyelination; (3) the behavioral CRS-R assessment score was positively
      correlated with white matter integrity in the fornix, uncinate fasciculus,
      pontine crossing tract, and posterior limb of internal capsule. Our results
      suggest that despite the widespread abnormalities of white matter following
      severe brain injury, the impairment of consciousness is likely to result from
      disruptions of key pathways that link brain regions in distributed networks.

PMID- 29362993
TI  - Regarding "Lethal hypothermia - a sometimes elusive diagnosis".

PMID- 29362994
TI  - Common Injuries in Professional Football Quarterbacks.
AB  - PURPOSE OF REVIEW: Professional football quarterbacks are at particular risk for
      upper extremity injuries due to the physical demands of their position coupled
      with the inherent risks associated with professional football. This review sought
      to evaluate current clinical literature to better characterize the injury profile
      unique to this athletic population. RECENT FINDINGS: Shoulder injuries are the
      most prevented upper extremity injury among professional football quarterbacks.
      The quarterback position is disproportionately impacted by shoulder injuries when
      compared to professional athletes at other positions. Moreover, contrary to other
      professional throwing athletes, the majority of upper extremity injuries in the
      professional quarterback result from direct contact as opposed to the throwing
      motion. The injury profile among professional quarterbacks is unique compared to
      other positions and other overhead professional throwing athletes. Overall, a
      paucity of high quality clinical evidence exists to support the management of
      injuries in this elite population.

PMID- 29362996
TI  - Successful surgical treatment of left atrioesophageal fistula following atrial
      ablation.
AB  - A 69-year-old male had catheter-based ablation for atrial fibrillation. He was
      admitted with high fever and had neurological disorder; he was diagnosed with
      atrioesophageal fistula by CT scan. Intraoperative findings showed that the
      fistula existed adjacent to the left lower pulmonary vein with a vegetation. The
      esophageal fistula was repaired, and the left atrial fistula was closed. A
      nasogastric tube tip was placed in the esophagus for decompression and advanced
      into the stomach for nutritional support. After vomiting, the patient showed loss
      of consciousness and left hemiplegia. CT scan revealed a micro-air embolism to
      the brain. The nasogastric tube tip was pulled back into the esophagus.
      Gastrointestinal fiberscopy showed a pinhole at the fistula, and a percutaneous
      endoscopic gastrostomy was made. After conservative treatment, the esophageal
      fistula was closed and mediastinitis was improved. He was discharged with a
      little neurological deficit.

PMID- 29362995
TI  - The Repaired Rotator Cuff: MRI and Ultrasound Evaluation.
AB  - PURPOSE OF REVIEW: The purposes of this review were to provide an overview of the
      current practice of evaluating the postoperative rotator cuff on imaging and to
      review the salient imaging findings of the normal and abnormal postoperative
      rotator cuff, as well as of postoperative complications. RECENT FINDINGS: The
      repaired rotator cuff frequently appears abnormal on magnetic resonance imaging
      (MRI) and ultrasound (US). Recent studies have shown that while the tendons
      typically normalize, they can demonstrate clinically insignificant abnormal
      imaging appearances for longer than 6 months. Features of capsular thickening or
      subacromial-subdeltoid bursal thickening and fluid distension were found to
      decrease substantially in the first 6-month postoperative period. MRI and US were
      found to be highly comparable in the postoperative assessment of the rotator
      cuff, although they had a lower sensitivity for partial thickness tears. Imaging
      evaluation of newer techniques such as patch augmentation and superior capsular
      reconstruction needs to be further investigated. MRI and US are useful in the
      postoperative assessment of the rotator cuff, not only for evaluation of the
      integrity of the rotator cuff, but also for detecting hardware complications and
      other etiologies of shoulder pain.

PMID- 29362997
TI  - TREM2 Ameliorates Neuronal Tau Pathology Through Suppression of Microglial
      Inflammatory Response.
AB  - As a recently identified susceptibility gene for Alzheimer's disease (AD),
      triggering receptor expressed on myeloid cells 2 (TREM2) encodes an immune
      receptor that is uniquely expressed on microglia, functioning as a modulator of
      microglial functions including phagocytosis and inflammatory response. Several
      lines of evidence suggest that TREM2 is upregulated and positively correlates
      with tau pathology in the brains of AD patients. Meanwhile, our recent study
      showed that knockdown of TREM2 markedly exacerbated neuronal tau
      hyperphosphorylation in the brains of P301S-tau transgenic mice, implying that
      TREM2 might exert a protective role against tau pathology under AD context.
      However, the precise mechanisms underlying this observation remain largely
      unclear. In this study, by employing a microglial-neuronal co-culture model, we
      showed that microglial inflammatory response induced by lipopolysaccharide led to
      tau hyperphosphorylation in neurons via activation of a major tau kinase glycogen
      synthase kinase 3beta, confirming the pathogenic effects of activated microglia
      on the progression of tau pathology. More importantly, by manipulating TREM2
      levels in microglia with a lentiviral-mediated strategy, we demonstrated that
      TREM2 ameliorated the pathological effects of activated microglia on neuronal tau
      hyperphosphorylation via suppression of microglial inflammatory response. Taken
      together, these findings uncover the underlying mechanisms by which TREM2
      protects against tau pathology and highlight TREM2 as a potential therapeutic
      target for AD.

PMID- 29362998
TI  - Cancer-associated retinopathy after surgery for breast cancer: a case report and
      review of the literature.
AB  - We herein report a 50-year-old Japanese woman with breast cancer who complained
      of blurred vision and central scotoma in her left eye on the 12th day after
      surgery. Subsequently, the sudden-onset binocular visual disorder progressed, and
      she was diagnosed with cancer-associated retinopathy (CAR) based on the clinical
      findings. Although her visual acuity temporarily improved following the start of
      adjuvant chemotherapy, reductions in her visual acuity progressed once again.
      After two courses of steroid pulse therapy initiated from the 59th day following
      the onset of CAR, although her visual field was still constricted, her binocular
      visual acuity improved from finger movement to 0.8 2 months later. The shorter
      the period from onset to treatment, the better the prognosis of the visual
      function. However, a diagnosis is often delayed because the incidence of this
      disease is very rare. Therefore, it is important to suspect CAR whenever a sudden
      visual disorder develops in cancer patients. Furthermore, treatment is believed
      to be effective even if steroid therapy is started up to 2 months from onset.

PMID- 29363000
TI  - Pituitary xanthogranulomas: clinical features, radiological appearances and post
      operative outcomes.
AB  - BACKGROUND: Xanthogranulomas are inflammatory masses most commonly found at
      peripheral sites such as the skin. Sellar and parasellar xanthogranulomas are
      rare and present a diagnostic challenge as they are difficult to differentiate
      from other sellar lesions such as craniopharyngiomas and Rathke's cleft cysts pre
      operatively. Their radiological imaging features are yet to be clearly defined,
      and clinical outcomes after surgery are also uncertain. This study reviews
      clinical presentation, radiological appearances, and clinical outcomes in a
      cohort of patients with pituitary xanthogranulomas. METHODS: A prospectively
      maintained pituitary surgery database was screened for histologically confirmed
      pituitary xanthogranulomas between May 2011-December 2016. Retrospective case
      note assessments were then performed by three independent reviewers. Patient
      demographics, clinical presentations, imaging, and clinical outcomes were
      analysed. RESULTS: During the study period 295 endoscopic endonasal pituitary
      surgeries were performed. Six patients had confirmed pituitary xanthogranulomas
      (2%). Patients most commonly presented with visual field deficits and/or
      endocrine dysfunction. Common imaging features included: a cystic consistency,
      hyperintensity on T1-weighted MR images, and contrast enhancement either
      peripherally (n = 3) or homogenously (n = 3). The most common pre-operative
      endocrine deficits were hyperprolactinaemia and hypoadrenalism (at least one of
      which was identified in 4/6 patients; 66%). Thirty-three percent (2/6) of
      patients presented with diabetes insipidus. The most common post-operative
      endocrinological deficits were adrenocortical dysfunction (66%) and gonadotropin
      deficiency (66%). Visual assessments normalised in all six patients post
      operatively. Gross total resection was achieved in all patients, and at median
      follow up of 33.5 months there were no cases of tumour recurrence. CONCLUSIONS:
      The prevalence of pituitary xanthogranulomas in our series is higher than that
      suggested in the literature. Surgery restored normal vision to all cases, however
      four patients (67%) required long-term hormonal replacement post-operatively.
      Imaging features such peripheral rim enhancement, a suprasellar tumour epicentre,
      and the absence of both calcification or cavernous sinus invasion were identified
      as potential indicators that together should alert clinicians to the possibility
      of pituitary xanthogranuloma when assessing patients with cystic sellar and
      parasellar tumours.

PMID- 29363001
TI  - The Impact of Triage Nurse-ordered Diagnostic Studies on Pediatric Emergency
      Department Length of Stay.
AB  - OBJECTIVE: To identify the need to revise the program triage nurse-ordered
      diagnostic tests in the emergency department (ED) of pediatric hospital, and to
      evaluate implementation of this program with three laboratory routine tests,
      namely blood, urine and stool, which the triage nurses ordered as relevant to
      pediatric patients' symptoms. METHODS: The authors retrospectively reviewed the
      data of patients who registered in their ED between December 2015 and April 2016,
      including the tests as per the orders by triage nurses, and the time they arrived
      and the time they had their final payments. A comparison was made of those, who
      stayed in the ED, with nurse-requested tests, to those without such tests.
      RESULTS: The review indicated the total number of subjects who presented in ED
      during the study period and were included in the study was 116,202; 65.4% with
      nurse-requested tests while 34.6% without such tests. On median, the length of
      their stay with nurse-requested tests was 229 min and without such tests was 244
      min, which has significant difference (P = 0.000). CONCLUSIONS: The results of
      this program were associated with a reduction in ED treatment which achieved the
      purpose to improve high patient flow in the emergency department. However, this
      intervention needs further studies to develop the nurse-ordered diagnostic
      studies program with more different clinical conditions and tests including
      triage nurses training and guideline.

PMID- 29363003
TI  - Correction to: Compositional design and Taguchi optimization of hardness
      properties in silicone-based ocular lenses.
AB  - The original version of this article unfortunately contained a mistake: The
      spelling of the Ebrahim Gafar-Zadehs' name was incorrect. The corrected name is
      given above.

PMID- 29363002
TI  - Bromodomain proteins GTE9 and GTE11 are essential for specific BT2-mediated sugar
      and ABA responses in Arabidopsis thaliana.
AB  - KEY MESSAGE: Global Transcription Factor Group E proteins GTE9 and GTE11 interact
      with BT2 to mediate ABA and sugar responses in Arabidopsis thaliana. BT2 is a BTB
      domain protein that regulates responses to various hormone, stress and metabolic
      conditions in Arabidopsis thaliana. Loss of BT2 results in plants that are
      hypersensitive to inhibition of germination by abscisic acid (ABA) and sugars.
      Conversely, overexpression of BT2 results in resistance to ABA and sugars. Here,
      we report the roles of BT2-interacting partners GTE9 and GTE11, bromodomain and
      extraterminal-domain proteins of Global Transcription Factor Group E, in BT2
      mediated responses to sugars and hormones. Loss-of-function mutants, gte9-1 and
      gte11-1, mimicked the bt2-1-null mutant responses; germination of all three
      mutants was hypersensitive to inhibition by glucose and ABA. Loss of either GTE9
      or GTE11 in a BT2 over-expressing line blocked resistance to sugars and ABA,
      indicating that both GTE9 and GTE11 were required for BT2 function. Co
      immunoprecipitation of BT2 and GTE9 suggested that these proteins physically
      interact in vivo, and presumably function together to mediate responses to ABA
      and sugar signals.

PMID- 29363004
TI  - Correction to: Cure kinetic study of methacrylate-POSS copolymers for ocular
      Lens.
AB  - The original version of this article unfortunately contained a mistake: the
      spelling of the Ebrahim Gafar-Zadehs' name was incorrect. The corrected name is
      given above.

PMID- 29362999
TI  - Abstracts of the 33rd International Austrian Winter Symposium : Zell am See,
      Austria. 24-27 January 2018.

PMID- 29363005
TI  - Polyphenols protect against age-associated apoptosis in female rat cochleae.
AB  - Dietary antioxidants, polyphenols, have been found to be beneficial in protecting
      against the generation of oxidative stress in various diseases associated with
      aging. Age-related hearing loss (AHL) is the number one neurodegenerative
      disorder on our aged population. Sprague-Dawley rats divided into five groups
      according to their age (3, 6, 12, 18 and 24 months old) and treated with 100
      mg/day/kg body weight of polyphenols were used. Then, cochleae were harvested to
      measure caspase activities (- 3, - 8 and - 9), caspase-3 gene expression, ATP
      levels, Bax, BcL-2 and p53 levels. 8-OHdG levels (marker of DNA oxidative damage)
      and annexin-V were also measured in cochleae. Increased levels of caspase-3 and 9
      in cochlea were observed with age and this effect was attenuated by polyphenol
      treatment. In addition, ATP and Bcl-2 levels in older rats were recovered after
      administration of polyphenols, while Bax and p53 levels protein decreased. Oral
      supplementation with polyphenols also reduces DNA oxidative damage of cochlear
      cell. Treatment with polyphenols inhibits the activation of age-related apoptotic
      signaling by decreasing oxidative stress inside the rat cochlea.

PMID- 29363006
TI  - 3 mm Senhance robotic hysterectomy: a step towards future perspectives.

PMID- 29363008
TI  - Troponin assessment in patients admitted to the emergency department with atrial
      fibrillation: which role in daily clinical practice?

PMID- 29363007
TI  - Technical and operational modifications required for evolving robotic programs
      performing anatomic pulmonary resection.
AB  - The objectives of this study are to review the complicated and often confusing
      technical changes required when converting from the Si robotic system to the Xi
      when performing pulmonary lobectomy and segmentectomy. We reviewed a prospective
      database of a consecutive series of patients who intended to undergo robotic
      lobectomy or segmentectomy by one surgeon. There were 101 lobectomies and 25
      segmentectomies performed on the Si robot in 2015-2016, and 95 lobectomies and 28
      segmentectomies in 2016 on the Xi robot. The two groups were similar for age,
      height, weight, pulmonary function, anatomic resections, and co-morbidities.
      Technical differences in robotic arm numbering, port placement, and
      instrumentation are shown below. Median docking time was shorter with the Xi
      robot [7.5 (95% CI 6-8) versus 10 (95% CI 9-12) min, p = 0.003] as was operation
      duration [114 (95% CI 104-123) versus 119 (95% CI 116-126) min, p = 0.041] and
      skin closure to room exit [12 (95% CI 10-24) versus 13 (95% CI 12-15) min, p =
      0.081]. Anesthesiologists expressed greater comfort with the Xi system, because
      the patient's head was not covered by the robot. Outcomes for Si and Xi
      operations such as median blood loss (20 cc versus 20 cc), transfusion rate (0
      versus 0), major complication rate (3.2 versus 3.3%), and the 30- and 90-day
      mortality were no different (one 30-day death in the Si group). The technical
      changes that are required for robotic Si-to-Xi conversion are shown. The Xi
      system may offer improved operational efficiency.

PMID- 29363009
TI  - Malignant Monckeberg medial calcific sclerosis.

PMID- 29363010
TI  - Visual discrimination of primate species based on faces in chimpanzees.
AB  - Many primate studies have investigated discrimination of individual faces within
      the same species. However, few studies have looked at discrimination between
      primate species faces at the categorical level. This study systematically
      examined the factors important for visual discrimination between primate species
      faces in chimpanzees, including: colour, orientation, familiarity, and perceptual
      similarity. Five adult female chimpanzees were tested on their ability to
      discriminate identical and categorical (non-identical) images of different
      primate species faces in a series of touchscreen matching-to-sample experiments.
      Discrimination performance for chimpanzee, gorilla, and orangutan faces was
      better in colour than in greyscale. An inversion effect was also found, with
      higher accuracy for upright than inverted faces. Discrimination performance for
      unfamiliar (baboon and capuchin monkey) and highly familiar (chimpanzee and
      human) but perceptually different species was equally high. After excluding
      effects of colour and familiarity, difficulty in discriminating between different
      species faces can be best explained by their perceptual similarity to each other.
      Categorical discrimination performance for unfamiliar, perceptually similar faces
      (gorilla and orangutan) was significantly worse than unfamiliar, perceptually
      different faces (baboon and capuchin monkey). Moreover, multidimensional scaling
      analysis of the image similarity data based on local feature matching revealed
      greater similarity between chimpanzee, gorilla and orangutan faces than between
      human, baboon and capuchin monkey faces. We conclude our chimpanzees appear to
      perceive similarity in primate faces in a similar way to humans. Information
      about perceptual similarity is likely prioritized over the potential influence of
      previous experience or a conceptual representation of species for categorical
      discrimination between species faces.

PMID- 29363011
TI  - A 5-mm trocar site paramedian early onset voluminous hernia: still in doubt?

PMID- 29363012
TI  - Distraction arthroplasty compared to other cartilage preservation procedures in
      patients with post-traumatic arthritis: a systematic review.
AB  - : Post-traumatic arthritis (PTA) is characterized by the deterioration of
      articular cartilage temporally associated with an articular injury. With a
      paucity of literature comparing joint preservation techniques, we performed a
      systematic review of the literature intending to describe and summarize the
      results of ankle distraction arthroplasty as it compares with studies on tibio
      talar microfracture, allograft, and autograft for ankle joint preservation in the
      post-traumatic population under 50 years of age. Research databases were searched
      and abstracts screened for relevance on our topic of interest. Abstracts meeting
      screening criteria with high interobserver reliability underwent full-manuscript
      review and coding for pertinent citation, study level, treatment, and outcome
      variables. Outcome variables for patient-reported pain scales, validated outcome
      measurement tools, radiographic progression, reoperation/re-treatment rates, and
      complication rates were recorded. Out of 105 unique citations, 10 publications
      were included. The distraction arthroplasty studies had 36 out of 181 patients
      requiring reoperation for complications (19.9%), while other joint-preserving
      procedures studies had 40 out of 177 patients requiring reoperations for
      complications (22.6%). Clinical outcome scores at mean follow-up time ranging
      from 2 to 10 years between studies were similar. Reported results for a variety
      of cartilage preservation procedures, including distraction arthroplasty, are
      satisfactory and reoperation rates for complication are similar. Limitations in
      available data and underlying study quality affect synthesis of the results
      therein. While distraction arthroplasty is an option for cartilage preservation
      in patients with PTA of the ankle, the technique is highly specialized which may
      affect the external validity. LEVEL OF EVIDENCE: III.

PMID- 29363013
TI  - The tibial bayonet method of wound closure.
AB  - Management of open lower limb fractures with soft tissue defects can be a
      technically challenging orthopaedic problem. Limited availability of orthoplastic
      services means that alternatives to the fix and flap concept are required in
      order to prevent infected non-unions from developing. The proposed 'bayonet
      apposition' allows the surgeon to temporarily shorten the limb without angulating
      the limb or creating a bone defect and removing viable bone. The viable bone
      edges are overlapped in a bayonet-like manner in order to appose the wound and
      skin edges. The limb length is restored by gradually distracting the bone
      segments once the soft tissues have healed. This is facilitated with a hexapod
      fixator for stabilization of the fracture and distraction. Prerequisites for
      utilizing this method are circumferential soft tissue damage to the lower limb
      with viable distal tissue. The bayonet method allows primary closure of a wound
      and rapid restoration of the native length of the limb.

PMID- 29363014
TI  - Letter to the Editor: Utility of Endoanal Ultrasonography in Assessment of
      Primary and Recurrent Anal Fistulas and for Detection of Associated Anal
      Sphincter Defects.

PMID- 29363015
TI  - Pancreaticoduodenectomy and Superior Mesenteric Vein Resection Without
      Reconstruction for Locally Advanced Pancreatic Cancer.

PMID- 29363016
TI  - Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy
      (HIPEC): a Single-Center Experience in Austria.
AB  - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) can significantly influence overall and disease-free
      survival in selected patients suffering from peritoneal surface malignancies
      (PSM) of various tumor entities. Because of the extent of the therapeutic
      approach, the associated morbidity and mortality and the multidisciplinarity
      needed, implementation of a CRS + HIPEC program at an institution is often
      challenging. METHODS: This single-center analysis included all patients (n = 60,
      34 female, 26 male) with PSM from various tumor primaries [colorectal cancer
      (15/60; 25%), appendix neoplasia (21/60; 35%), and others (24/60; 40%)] treated
      with CRS + HIPEC at our institution between 2006 and 2014. Charts were reviewed
      for preoperative patient evaluation, procedure-specific and tumor-specific
      parameters, morbidity, mortality, tumor recurrence and patients' overall (OS),
      and disease-free survival (DFS). RESULTS: In 57 of the 60 patients included in
      the investigation (57/60; 95%), a radical resection (CC 0/1) was achieved. Median
      operating time was 559 min (253-900) with a median need of packed red blood cells
      of 1.1 (0-7) or fresh frozen plasma of 4.4 (0-20) concentrates. Twenty (33.3%)
      patients experienced 24 Dindo-Clavien grade III/IV complications (24/63; 38.1%).
      Postoperative 30- and 90-day mortality was 0% in our study population. Five-year
      OS was 43%, 5-year DFS 33%. CONCLUSIONS: Due to thorough preoperative patient
      evaluation, strict inclusion and exclusion criteria, and intense collaboration
      with other specialties, we were able to achieve an excellent 5-year OS of 43%
      with a CC score of 0/1 in 95% of our patient population. We were able to
      demonstrate the feasibility, efficacy, and safety of CRS + HIPEC in patients
      suffering from PSM at our institution.

PMID- 29363017
TI  - Esophagobronchial Fistula as the Initial Manifestation of an Esophageal Cancer:
      Radiological Demonstration.

PMID- 29363018
TI  - Surgical Anatomy of the Superior Mesenteric Vessels Related to
      Pancreaticoduodenectomy: a Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Mesopancreas dissection with central vascular ligation
      and the superior mesenteric artery (SMA)-first approach represent the cornerstone
      of current principles for radical resection for pancreatic head cancer. The
      surgeon dissecting around the SMV and SMA should be aware regarding the
      anatomical variants in this area. The aims of this systematic review and meta
      analysis are to detail the surgical anatomy of the superior mesenteric vessels
      and to propose a standardized terminology with impact in pancreatic cancer
      surgery. METHODS: We conducted a systematic search to identify all published
      studies in PubMed/MEDLINE and Google Scholar databases from their inception up to
      March 2017. RESULTS: Seventy-eight studies, involving a total of 18,369
      specimens, were included. The prevalence of the mesenteric-celiac trunk,
      replaced/accessory right hepatic artery (RRHA), common hepatic artery, and SMV
      inversion was 2.8, 13.2, 2.6, and 4.1%, respectively. The inferior
      pancreaticoduodenal artery has its origin into the first jejunal artery, SMA, and
      RRHA, in 58.7, 35.8, and 1.2% of cases, respectively. The SMV lacks a common
      trunk in 7.5% of cases. The first jejunal vein has a trajectory posterior to the
      SMA in 71.8% of cases. The left gastric vein drains into the portal vein in 58%,
      in splenic vein (SV) in 35.6%, and into the SV-PV confluence in 5.8% of cases.
      CONCLUSIONS: Complex pancreaticoduodenal resections require detailed knowledge of
      the superior mesenteric artery and vein, which is significantly different from
      the one presented in the classical textbooks of surgery. We are proposing the
      concept of the first jejunopancreatic vein which impacts the current oncological
      principles of pancreatic head cancer resection.

PMID- 29363019
TI  - Liver Transplantation and Liver Resection for Cirrhotic Patients with
      Hepatocellular Carcinoma: Comparison of Long-Term Survivals.
AB  - BACKGROUND: Both liver transplantation (LT) and liver resection (LR) represent
      curative treatment options for hepatocellular carcinoma (HCC) in patients with
      liver cirrhosis. In this study, we have compared outcomes between historical and
      more recent patient cohorts scheduled either for LT or LR, respectively. METHODS:
      Clinicopathological data of all patients with HCC and cirrhosis who underwent LT
      or LR between 1989 and 2011 were evaluated. Overall survival of patients with HCC
      within the Milan criteria (MC) was analyzed focusing on changes between different
      time periods. RESULTS: In total, 364 and 141 patients underwent LT and LR for HCC
      in cirrhosis, respectively. Among patients with HCC within MC, 214 and 59
      underwent LT and LR, respectively. Postoperative morbidity (37 vs. 11%, P <
      .0001), but not mortality (3 vs. 1%, P = .165), was higher after LR than after LT
      for HCC within MC. In the period 1989-2004, overall survival (OS) was
      significantly higher in patients who underwent LT compared to LR for HCC within
      MC (5-year OS: 77 vs. 36%, P < .0001). Interestingly, in the more recent period
      2005-2011, OS was comparable between LT and LR for HCC within MC (5-year OS: 73
      vs. 61%, P = .07). CONCLUSION: We have noted an improvement of outcomes among
      patients selected for partial hepatectomy in recent years that were comparable to
      stable results after LT in cirrhotic patients with HCC. Whether those
      improvements are due to advances in liver surgery, optimized perioperative
      managament for patients with liver cirrhosis, and the development of modern
      multimodal treatment strategies for the recurrent lesions appears plausible.

PMID- 29363020
TI  - Health State Utility Values for Ileostomies and Colostomies: a Systematic Review
      and Meta-Analysis.
AB  - BACKGROUND: Ileostomies and colostomies may affect the quality of life of
      patients after colorectal surgery; however, the impact has been difficult to
      quantify using questionnaire-based measures. Utilities reflect patient
      preferences for health states and provide an alternate method of quality of life
      assessment. We aimed to systematically review the literature on utilities for
      ileostomy and colostomy health states. METHODS: We searched MEDLINE, EMBASE, and
      EBM Reviews (to August 16, 2017) to identify studies reporting utilities for
      colostomies or ileostomies using direct or indirect, preference-based elicitation
      tools. We categorized utilities based on elicitation group (patients with stoma,
      patients without stoma, healthcare providers, general population) and tool. We
      pooled utilities using random effects models to determine mean utilities for each
      elicitation group and tool. RESULTS: We identified ten studies reporting
      colostomy utilities and three studies reporting ileostomy utilities. Utilities
      were most commonly obtained using direct elicitation measures administered to
      individuals with an understanding of the health state. Patients with stomas and
      providers gave high utility ratings for the colostomy state (range 0.88-0.92 and
      0.86-0.92, respectively, using direct elicitation tools). Ileostomy utilities
      obtained from patients following surgery and from providers also demonstrated
      high values placed on the ileostomy health state (range 0.88-1.0). CONCLUSIONS:
      Following stoma surgery, values placed on quality of life are similar to those
      obtained from patients with conditions such as asthma and allergies or
      individuals of similar age without chronic conditions. This confirms the findings
      of questionnaire-based studies, which report minimal long-term decrements to
      overall quality of life among stomates.

PMID- 29363021
TI  - Pathognomonic Signs for Hepatic Hydatid Disease: Snake Sign and Spin Sign.

PMID- 29363022
TI  - Economic Impact in Medicaid Beneficiaries with Schizophrenia and Cardiometabolic
      Comorbidities Treated with Once-Monthly Paliperidone Palmitate vs. Oral Atypical
      Antipsychotics.
AB  - OBJECTIVE: The objective of this study was to compare persistence, costs, and
      healthcare resource utilization in patients with schizophrenia and
      cardiometabolic comorbidities treated with once-monthly paliperidone palmitate or
      an oral atypical antipsychotic. METHODS: Medicaid data from six states (07/2009
      03/2015) were used to identify adults with schizophrenia and cardiometabolic
      comorbidities initiated on once-monthly paliperidone palmitate or an oral
      atypical antipsychotic (index date) on 01/2010 or after. Persistence to index
      medication at 12 months (no gap >= 90 days) was compared between patients taking
      once-monthly paliperidone palmitate and an oral atypical antipsychotic using Chi
      squared tests. The 12-month post-index healthcare costs and healthcare resource
      utilization were compared using multivariate ordinary least squares and Poisson
      regression, respectively. RESULTS: Selected patients taking once-monthly
      paliperidone palmitate (n = 371) were younger (mean age: 45.0 vs. 47.5 years,
      standardized difference = 24%) than patients taking oral atypical antipsychotics
      (n = 8296). Persistence at 12 months was higher in patients taking once-monthly
      paliperidone palmitate (40 vs. 33%, p = 0.006). Adjusted all-cause medical costs
      were lower in patients taking once-monthly paliperidone palmitate vs. patients
      taking oral atypical antipsychotics (mean monthly cost differences = US $ - 369,
      p = 0.004) while all-cause pharmacy costs were higher (mean monthly cost
      differences = US $279, p < 0.001), resulting in no significant difference in
      total costs (mean monthly cost differences = US $ - 90, p = 0.357). No
      significant difference was observed in cardiometabolic comorbidity-related
      pharmacy or medical costs. Compared with patients taking oral atypical
      antipsychotics, patients taking once-monthly paliperidone palmitate had more
      schizophrenia-related outpatient visits (incidence rate ratio = 1.44, p < 0.001)
      but fewer cardiometabolic comorbidity-related inpatient admissions (incidence
      rate ratio = 0.73, p < 0.001) with shorter lengths of stay (incidence rate ratio
      = 0.72, p = 0.020), and fewer cardiometabolic comorbidity-related long-term care
      admissions (incidence rate ratio = 0.56, p = 0.016). CONCLUSIONS: Medicaid
      beneficiaries with schizophrenia and cardiometabolic comorbidities who were
      initiated on once-monthly paliperidone palmitate had similar 12-month total
      healthcare costs compared with oral atypical antipsychotics. Cardiometabolic
      comorbidity-related utilization of inpatient and long-term care services was
      lower in patients taking once-monthly paliperidone palmitate.

PMID- 29363023
TI  - 2017 SEOM guidelines: a multidisciplinary approach.

PMID- 29363025
TI  - CNS-Targeted Antiretroviral Strategies: When Are They Needed and What to Choose.
AB  - PURPOSE OF REVIEW: Neurocognitive disorders are not uncommon in HIV-positive
      patients but their pathogenesis is multifactorial and incompletely understood.
      After excluding contributing comorbidities, several factors may impair
      neurocognition including severe immune suppression, incomplete antiviral
      efficacy, drugs' persistent immune activation, vascular abnormalities, and drugs'
      neurotoxicity. The effectiveness of targeted antiretroviral strategies on these
      risk factors is unknown. RECENT FINDINGS: Recent studies support the idea that
      residual cerebrospinal fluid HIV RNA in the setting of plasma viral suppression
      is associated with compartmental immune activation but the link to neuronal
      damage is debated. Some authors have reported an incomplete antiviral efficacy in
      macrophage-derived cells but targeted antiretroviral regimen switches have not
      been performed. Additionally, improvements in neurocognition using drugs with
      better central nervous system penetration or maraviroc (associated with favorable
      immunological properties) have been observed in pilot studies. Trials evaluating
      specific interventions for cardiovascular health (including brain white matter
      abnormalities) and neurotoxicity of antiretrovirals are warranted. Central
      nervous system-targeted antiretroviral strategies are needed in patients with
      uncontrolled cerebrospinal HIV replication, and they may be suggested in subjects
      with low CD4 nadir, individuals carrying drug-resistant viruses, and those with
      compartmental immune activation.

PMID- 29363026
TI  - Low-Dose Ponatinib in Intolerant Chronic Myeloid Leukemia Patients: A Safe and
      Effective Option.

PMID- 29363024
TI  - Cloning, expression, purification and spectrophotometric analysis of lanosterol
      14-alpha demethylase from Leishmania braziliensis (LbCYP51).
AB  - Leishmaniasis, a neglected tropical disease, is a major cause of morbidity and
      mortality worldwide. Of the three main clinical forms, cutaneous leishmaniasis
      (CL) is the most common and 40 million people are at risk in the endemic areas.
      Currently, the available drugs to fight leishmaniasis have high toxicity and poor
      efficiency. Then, it is very important to search for effective and safe drugs
      that would target essential enzymes from the parasite, such as lanosterol 14
      alpha demethylase (CYP51, EC 1.14.13.70) from Leishmania braziliensis. Because
      most drug design efforts have been directed for Leishmania non-braziliensis
      species, there is no structural or kinetic data regarding L. braziliensis CYP51.
      Herein, we present for the first time molecular biology efforts and purification
      protocol to obtain the enzyme LbCYP51. These results lay the ground for future
      investigation of drugs against this target.

PMID- 29363027
TI  - Pharmacodynamics, Safety, and Tolerability of the NHE3 Inhibitor Tenapanor: Two
      Trials in Healthy Volunteers.
AB  - BACKGROUND: Tenapanor, a small molecule with minimal systemic availability, is a
      first-in-class sodium/hydrogen exchanger 3 (NHE3) inhibitor that acts in the gut.
      Here, we evaluate the pharmacodynamics and safety of tenapanor in healthy adults.
      METHODS: Two phase I, single-center, randomized, double-blind, placebo-controlled
      studies were performed. The first study assessed single-ascending oral tenapanor
      doses of 10, 50, 150, 450, and 900 mg (n = 8 per group; six tenapanor, two
      placebo) and multiple ascending doses over 7 days of 3, 10, 30, and 100 mg q.d.
      (n = 10 per group; eight tenapanor, two placebo). In the second study, different
      tenapanor regimens were evaluated over 7 days (n = 15 per group; 12 tenapanor,
      three placebo): 15 mg twice daily (b.i.d.), 30 mg once daily (q.d.), 30 mg
      b.i.d., 30 mg three times daily (t.i.d.), 60 mg b.i.d., escalating b.i.d. dose
      (daily total 30-90 mg), 30 mg b.i.d. with psyllium. RESULTS: Tenapanor produced
      generally dose-dependent increases in stool sodium excretion and decreases in
      urinary sodium excretion versus placebo; in addition, twice-daily dosing appeared
      to have a greater effect on sodium absorption than once-daily dosing with an
      equivalent daily dose. Tenapanor softened stool consistency and increased stool
      frequency and weight from baseline versus placebo. Tenapanor concentrations were
      below the quantification limit (0.5 ng/ml) in 98.5% of 895 plasma samples.
      Adverse events were mild or moderate in severity, and were typically
      gastrointestinal in nature. There were no clinically relevant changes in serum
      electrolytes. CONCLUSIONS: Tenapanor was well tolerated and resulted in reduced
      intestinal sodium absorption and softer stool consistency versus placebo.
      Systemic exposure to tenapanor was minimal. These results support potential use
      of tenapanor in patients who could benefit from modification of gastrointestinal
      sodium balance. CLINICALTRIALS. GOV IDENTIFIERS: NCT02819687, NCT02796131.

PMID- 29363029
TI  - Cognitive load effects on early visual perceptual processing.
AB  - Contrast-based early visual processing has largely been considered to involve
      autonomous processes that do not need the support of cognitive resources.
      However, as spatial attention is known to modulate early visual perceptual
      processing, we explored whether cognitive load could similarly impact contrast
      based perception. We used a dual-task paradigm to assess the impact of a
      concurrent working memory task on the performance of three different early visual
      tasks. The results from Experiment 1 suggest that cognitive load can modulate
      early visual processing. No effects of cognitive load were seen in Experiments 2
      or 3. Together, the findings provide evidence that under some circumstances
      cognitive load effects can penetrate the early stages of visual processing and
      that higher cognitive function and early perceptual processing may not be as
      independent as was once thought.

PMID- 29363028
TI  - Implicit processing during change blindness revealed with mouse-contingent and
      gaze-contingent displays.
AB  - People often miss salient events that occur right in front of them. This
      phenomenon, known as change blindness, reveals the limits of visual awareness.
      Here, we investigate the role of implicit processing in change blindness using an
      approach that allows partial dissociation of covert and overt attention.
      Traditional gaze-contingent paradigms adapt the display in real time according to
      current gaze position. We compare such a paradigm with a newly designed mouse
      contingent paradigm where the visual display changes according to the real-time
      location of a user-controlled mouse cursor, effectively allowing comparison of
      change detection with mainly overt attention (gaze-contingent display; Experiment
      2) and untethered overt and covert attention (mouse-contingent display;
      Experiment 1). We investigate implicit indices of target detection during change
      blindness in eye movement and behavioral data, and test whether affective
      devaluation of unnoticed targets may contribute to change blindness. The results
      show that unnoticed targets are processed implicitly, but that the processing is
      shallower than if the target is consciously detected. Additionally, the partial
      untethering of covert attention with the mouse-contingent display changes the
      pattern of search and leads to faster detection of the changing target. Finally,
      although it remains possible that the deployment of covert attention is linked to
      implicit processing, the results fall short of establishing a direct connection.

PMID- 29363030
TI  - A comparison of selenium concentrations in selected organs of wild boar (Sus
      scrofa) from industrialized and non-industrialized regions of Poland.
AB  - The aim of this study was to compare selenium concentration in the liver and
      kidneys of wild boar inhabiting industrialized and non-industrialized regions of
      Poland. Selenium concentrations in organs were determined using
      spectrofluorometric method. In all the animals studied, Se concentrations were a
      few times lower than in kidneys which may indicate too low content of this
      element either in the boar's diet or the presence of a poorly absorbable form of
      Se. No statistically significant differences were noted in the mean Se
      concentrations in the liver and kidney of wild boar from industrialized and non
      industrialized areas. In the case of wild boar, it seems that the level of
      selenium in their organs is more dependent on geochemical conditions in the
      specific feeding ground than on the scale of regional industrialization, and that
      this situation is most likely related to the specificity of wild boar feeding.

PMID- 29363031
TI  - Effect of intermittent operation model on the function of soil infiltration
      system.
AB  - To enhance denitrification in a process of solute infiltration through a soil, a
      two-section mixed-medium soil infiltration system (TMSIS) for urban non-point
      pollution was developed. The artificial aerobic respiration and nitrification
      took place in the upper aerobic section (AES), while grass powders and sawdust
      were mixed in the bottom anaerobic section (ANS) to supply organic carbon source
      for denitrification bacteria, and the reduction was increased by iron addition in
      the ANS. Measured resident concentrations from the bottom of each ANS column were
      assumed to represent mean values averaged over the column cross-sectional area.
      The TMSIS with hydraulic loading rates (HLR) of 0.32, 0.24, and 0.16 m3 m-2 day-1
      and with wetting-drying ratio (RWD) of 1.0 showed remarkable removal efficiencies
      for chemical oxygen demand (COD), NH4+-N, and TP, respectively. The hydraulic
      loading rate of 0.32 m3 m-2 day-1 was selected as the optimal HLR due to the high
      contaminated runoff treatment efficiency. When RWD was 1.0, 0.5, or 0.2 with
      hydraulic loading rate of 0.32 m3 m-2 day-1, the TMSIS could treat synthetic
      urban runoff contaminants very well. The corresponding effluent water met the
      China's national quality standard for class V surface water. The wetting-drying
      ratio of 0.5 with hydraulic loading of 0.32 m3 m-2 day-1 was selected as the
      optimal operation conditions for the TMSIS. Aerobic respiration and nitrification
      mainly took place in the upper AES, in which most of the COD and the NH4+-N were
      removed. Mixed sawdust and grass powders used as a carbon source and
      heterotrophic denitrification were put at the bottom of the ANS. The developed
      TMSIS has the potential to be applied for urban non-point pollution removal.

PMID- 29363032
TI  - The pH-dependent toxicity of triclosan to five aquatic organisms (Daphnia magna,
      Photobacterium phosphoreum, Danio rerio, Limnodrilus hoffmeisteri, and Carassius
      auratus).
AB  - Triclosan (TCS) is an antibacterial and antifungal agent widely used in personal
      care products, and it has been frequently detected in the aquatic environment. In
      the present study, the acute toxicity of TCS to Daphnia magna, Photobacterium
      phosphoreum, Danio rerio, and Limnodrilus hoffmeisteri was assessed under
      different pH conditions. Generally, TCS was more toxic to the four aquatic
      organisms in acidic medium. The LC50 values for D. magna and D. rerio were
      smaller among the selected species, suggesting that D. magna and D. rerio were
      more sensitive to TCS. In addition, the oxidative stress-inducing potential of
      TCS was evaluated in Carassius auratus at three pH values. Changes of superoxide
      dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) level, and
      malondialdehyde (MDA) content were commonly observed in all TCS exposure groups,
      indicating the occurrence of oxidative stress in the liver of C. auratus. The
      integrated biomarker response (IBR) index revealed that a high concentration of
      TCS induced great oxidative stress in goldfish under acidic condition. This work
      supplements the presently available data on the toxicity data of TCS, which would
      provide some useful information for the environmental risk assessment of this
      compound.

PMID- 29363033
TI  - Identification of the driving factors' influences on regional energy-related
      carbon emissions in China based on geographical detector method.
AB  - To investigate the influences of different factors on spatial heterogeneity of
      regional carbon emissions, we firstly studied the spatial-temporal dynamics of
      regional energy-related carbon emissions using global Moran's I and Getis-Ord Gi
      and applied geographical detector model to explain the spatial heterogeneity of
      regional carbon emissions. Some conclusions were drawn. Regional carbon emissions
      showed significant global and local spatial autocorrelation. The carbon emissions
      were greater in eastern and northern regions than in western and southern
      regions. Fixed assets investment and economic output had been the main
      contributing factors over the study period, and economic output had been
      decreasing its influence. Industrial structure's influence showed a decrease
      trend and became smaller in 2015. The results of the interaction detections in
      2015 can be divided into two types: enhance and nonlinear, and enhance and
      bivariate. The interactive influences between technological level and fixed
      assets investment, economic output and technological level, population size and
      technological level, and economic output and economic development were greater
      than others. Some policy recommendations were proposed.

PMID- 29363034
TI  - Multi-sensor temporal assessment of tropospheric nitrogen dioxide column
      densities over Pakistan.
AB  - Spatial and temporal distributions of tropospheric NO2 vertical column densities
      over Pakistan during the period 2002-2014 are discussed. Data products from three
      satellite instruments SCIAMACHY, OMI, and GOME-2 are used to prepare a database
      of tropospheric NO2 column densities over Pakistan and temporal evolution is also
      determined. Plausible NO2 sources in Pakistan are also discussed. The results
      show a large NO2 growth over all provinces and the major cities of Pakistan
      except the megacity of Karachi. Decline in industrial activities due to energy
      crises, worsening law and order situation, terrorist attacks, and political
      instability was explored as the main factor for lower NO2 VCDs over Karachi City.
      The overall increase can be attributed to the anthropogenic emissions over the
      areas with high population, traffic density, and industrial activities. Source
      identification revealed that use of fossil fuels by various sectors including
      power generation, vehicles, and residential sectors along with agriculture fires
      are among significant sources of NO2 emissions in Pakistan. Existing emission
      inventories such as EDGARv4.2 and MACCity largely underestimate the true
      anthropogenic NOx emissions in Pakistan. This study may provide vital information
      to policy makers and regulatory authorities in developing countries, including
      Pakistan, in order to devise effective air pollution abatement policies.

PMID- 29363035
TI  - Incorporation of corn straw biochar inhibited the re-acidification of four acidic
      soils derived from different parent materials.
AB  - The effect of corn straw biochar on inhibiting the re-acidification of acid soils
      derived from different parent materials due to increased soil pH buffering
      capacity (pHBC) was investigated using indoor incubation and simulated
      acidification experiments. The incorporation of the biochar increased the pHBC of
      all four soils due to the increase in soil cation exchange capacity (CEC). When
      5% biochar was incorporated, the pHBC was increased by 62, 27, 32, and 24% for
      the Ultisols derived from Tertiary red sandstone, Quaternary red earth, granite,
      and the Oxisol derived from basalt, respectively. Ca(OH)2 and the biochar were
      added to adjust the soil pH to the same values, and then HNO3 was added to
      acidify these amended soils. The results of this simulated acidification
      indicated that the decrease in soil pH induced by HNO3 was lower for the
      treatments with the biochar added than that of the treatments with Ca(OH)2 added.
      Consequently, the biochar could inhibit the re-acidification of the amended acid
      soils due to the increased resistance of the soils to acidification when the pH
      of amended soil was higher than 5.5. The inhibiting effectiveness of the biochar
      on soil re-acidification was greater in the Ultisol derived from Tertiary red
      sandstone due to its lower clay and organic matter contents and CEC than the
      other three soils. The incorporation of the biochar also decreased the
      potentially reactive Al, i.e., exchangeable Al, organically bound Al, and sorbed
      hydroxyl Al, compared with the treatments amended with Ca(OH)2. Therefore, the
      incorporation of corn straw biochar not only inhibited the re-acidification of
      amended acid soils through increasing their resistance to acidification but also
      decreased the potential of Al toxicity generated during re-acidification.

PMID- 29363036
TI  - Intercalated theophylline-smectite hybrid for pH-mediated delivery.
AB  - On the basis of their large specific surface areas, high adsorption and cation
      exchange capacities, swelling potential and low toxicity, natural smectite clays
      are attractive substrates for the gastric protection of neutral and cationic
      drugs. Theophylline is an amphoteric xanthine derivative that is widely used as a
      bronchodilator in the treatment of asthma and chronic obstructive pulmonary
      disease. This study considers the in vitro uptake and release characteristics of
      the binary theophylline-smectite system. The cationic form of theophylline was
      readily ion exchanged into smectite clay at pH 1.2 with a maximum uptake of 67 +/
      2 mg g-1. Characterisation of the drug-clay hybrid system by powder X-ray
      diffraction analysis, Fourier transform infrared spectroscopy, differential
      scanning calorimetry and scanning electron microscopy confirmed that the
      theophylline had been exclusively intercalated into the clay system in an
      amorphous form. The drug remained bound within the clay under simulated gastric
      conditions at pH 1.2; and the prolonged release of approximately 40% of the drug
      was observed in simulated intestinal fluid at pH 6.8 and 7.4 within a 2-h
      timeframe. The incomplete reversibility of the intercalation process was
      attributed to chemisorption of the drug within the clay lattice. These findings
      indicate that smectite clay is a potentially suitable vehicle for the safe
      passage of theophylline into the duodenum. Protection from absorption in the
      stomach and subsequent prolonged release in the small intestine are advantageous
      in reducing fluctuations in serum concentration which may impact therapeutic
      effect and toxicity.

PMID- 29363037
TI  - Erratum to: Irreversible phenotypic perturbation and functional impairment of B
      cells during HIV-1 infection.
AB  - The original version of this article unfortunately contained a mistake. One of
      the authors of this article has been misspelled. Xiaoyang Zhang should be Xiaoyan
      Zhang. The update is also provided here.

PMID- 29363038
TI  - Responses to emerging and re-emerging infectious diseases: One world, One health.

PMID- 29363040
TI  - Semaglutide: First Global Approval.
AB  - Novo Nordisk has developed a subcutaneous formulation of semaglutide
      (Ozempic(r)), a modified human glucagon-like peptide-1 (GLP-1) analogue, for the
      treatment of type 2 diabetes mellitus. It has been developed using Novo Nordisk's
      proprietary protein-acylation technology, and is administered using an injection
      device. Semaglutide lowers blood glucose by stimulating the release of insulin
      and also lowers body weight. Once-weekly subcutaneous semaglutide has recently
      been approved in the US, Puerto Rico and Canada, and has received a positive
      opinion in the EU for the treatment of patients with type 2 diabetes. It will be
      launched as the Ozempic(r) Pen, a pre-filled device. Semaglutide is also under
      regulatory review in Japan and Switzerland for the treatment of type 2 diabetes.
      Clinical development for obesity, non-alcoholic steatohepatitis and non-alcoholic
      fatty liver disease is underway worldwide. This article summarizes the milestones
      in the development of semaglutide leading to this first approval for type 2
      diabetes.

PMID- 29363039
TI  - Effects of progesterone on the neonatal brain following hypoxia-ischemia.
AB  - Progesterone displays a strong potential for the treatment of neonatal hypoxic
      ischemic encephalopathy since it has been shown to be beneficial in the treatment
      of the central nervous system injuries in adult animals. Here, we evaluated the
      effects of the administration of progesterone (10 mg/kg) in seven-days-old male
      Wistar rats submitted to neonatal hypoxia-ischemia (HI). Progesterone was
      administered immediately before ischemia and/or 6 and 24 h after the onset of
      hypoxia. The body weight of the animals, the volume of brain lesion and the
      expression of p-Akt and procaspase-3 in the hippocampus were evaluated. All
      animals submitted to HI showed a reduction in the body weight. However, this
      reduction was more remarkable in those animals which received progesterone before
      surgery. Administration of progesterone was unable to reduce the volume of brain
      damage caused by HI. Moreover, no significant differences were observed in the
      expression of p-Akt and procaspase-3 in animals submitted to HI and treated with
      either progesterone or vehicle. In summary, progesterone did not show a
      neuroprotective effect on the volume of brain lesion in neonatal rats submitted
      to hypoxia-ischemia. Furthermore, progesterone was unable to modulate p-Akt and
      procaspase-3 signaling pathways, which may explain the absence of
      neuroprotection. On the other hand, it seems that administration of progesterone
      before ischemia exerts some systemic effect, leading to a remarkable reduction in
      the body weight.

PMID- 29363041
TI  - Correction to: Daratumumab: A Review in Relapsed and/or Refractory Multiple
      Myeloma.
AB  - The author has alerted us to the following error in Sect. 4.2.2.1, and the
      following correction should be noted.

PMID- 29363042
TI  - Potential Role of Extracellular Vesicles in the Pathophysiology of Drug
      Addiction.
AB  - Extracellular vesicles (EVs) are small vesicles secreted by cells and are known
      to carry sub-cellular components including microRNA, proteins, and lipids. Due to
      their ability to transport cargo between cells, EVs have been identified as
      important regulators of various pathophysiological conditions and can therefore
      influence treatment outcomes. In particular, the significance of microRNAs in EV
      mediated cell-cell communication is well-documented. While the influence of EVs
      and the cargo delivered by EVs has been extensively reviewed in other
      neurological disorders, the available literature on the potential role of EVs in
      the pathophysiology of drug addiction has not been reviewed. Hence, in this
      article, the known effects of commonly abused drugs (ethanol, nicotine, opiates,
      cocaine, and cannabinoids) on EV secretion have been reviewed. In addition, the
      potential role of drugs of abuse in affecting the delivery of EV-packaged
      microRNAs, and the subsequent impact on neuronal health and continued drug
      dependence, has been discussed.

PMID- 29363045
TI  - Percutaneous closure of iatrogenic ventricular septal rupture following septal
      branch obstruction during elective coronary angioplasty.

PMID- 29363043
TI  - Functional Characterization of Novel Circular RNA Molecule, circzip-2 and Its
      Synthesizing Gene zip-2 in C. elegans Model of Parkinson's Disease.
AB  - Circular RNAs (circRNAs) are peculiar non-coding RNA molecules which are known to
      be present across taxa. Considering the body of evidence that establishes
      critical functions of non-coding RNA molecules, we endeavored to study circRNAs
      in the context of Parkinson's disease (PD). Employing transgenic C. elegans model
      of PD, we used RNase R-mediated cleavage of linear RNA followed by divergent
      primer-based amplifications towards identifying circzip-2, a novel circRNA
      molecule. We went on to sequence circzip-2 which is synthesized from functionally
      important gene zip-2. Studying RNAi-induced knockdown conditions of zip-2, we
      observed a reduced aggregation of alpha-synuclein protein along with an enhanced
      lifespan of the worms. We further carried out transcriptome analysis of zip-2
      silenced worms, which suggested that zip-2 might be functioning via Daf-16
      pathway. Further interaction studies revealed that circzip-2 possibly sponges
      microRNA molecule miR-60 towards asserting an important role in various processes
      associated with PD.

PMID- 29363046
TI  - The boxer world heavyweight champion Primo Carnera portrayed by Giacomo Balla.

PMID- 29363044
TI  - Reactive Astrocytes in Glioblastoma Multiforme.
AB  - Despite the multidisciplinary integration in the therapeutic management of
      glioblastoma multiforme (GBM), the prognosis of GBM patients is poor. There is
      growing recognition that the cells in the tumor microenvironment play a vital
      role in regulating the progression of glioma. Astrocytes are an important
      component of the blood-brain barrier (BBB) as well as the tripartite synapse
      neural network to promote bidirectional communication with neurons under
      physiological conditions. Emerging evidence shows that tumor-associated reactive
      astrocytes interact with glioma cells and facilitate the progression, aggression,
      and survival of tumors by releasing different cytokines. Communication between
      reactive astrocytes and glioma cells is further promoted through ion channels and
      ion transporters, which augment the migratory capacity and invasiveness of tumor
      cells by modifying H+ and Ca2+ concentrations and stimulating volume changes in
      the cell. This in part contributes to the loss of epithelial polarization,
      initiating epithelial-mesenchymal transition. Therefore, this review will
      summarize the recent findings on the role of reactive astrocytes in the
      progression of GBM and in the development of treatment-resistant glioma. In
      addition, the involvement of ion channels and transporters in bridging the
      interactions between tumor cells and astrocytes and their potential as new
      therapeutic anti-tumor targets will be discussed.

PMID- 29363047
TI  - New perspectives on the definition and management of polycystic ovary syndrome.
AB  - BACKGROUND: There is a growing debate on the opportunity of improving the
      understanding in the diagnosis and management of polycystic ovary syndrome
      (PCOS). OBJECTIVE: This review article summarizes recent research related to the
      definition of polycystic ovary syndrome (PCOS). METHODS: Review of the recent
      literature on the topic. RESULTS: New ideas on the definition of
      hyperandrogenism, based on new scientific data and clinical perspectives are
      presented. (i) In fact, recent studies have pointed out the need to improve the
      concept of androgen excess by using a larger androgen profile, rather than simply
      measuring the testosterone blood levels. (ii) Due to the poor correlation between
      androgen blood levels and the degree of hirsutism, it is proposed that the
      definition of hyperandrogenism should be based on the presence of blood androgen
      excess and hirsutism, considered separately, because their pathophysiological
      mechanisms may differ according to the different phenotypes of PCOS. (iii) The
      potential role of obesity in favoring the development of PCOS during adolescence
      is also discussed and the concept of "PCOS secondary to obesity" is developed.
      (iv) Finally, the need for greater appropriateness in the evaluation of possible
      coexistence is highlighted, in patients with PCOS who have fasting or glucose
      stimulated very high insulin levels, or severe insulin-resistant states.
      CONCLUSIONS: Based on what was discussed in this review, we believe that there
      are margins for modifying some of the current criteria that define the various
      PCOS phenotypes.

PMID- 29363048
TI  - Association of serum betatrophin with fibroblast growth factor-21 in women with
      polycystic ovary syndrome.
AB  - PURPOSE: Betatrophin and fibroblast growth factor-21 (FGF-21), which are recently
      discovered members of hepatokine/adipokine family, have been proposed to be
      associated with some metabolic disorders in which insulin resistance plays a
      major role. METHODS: We aimed to investigate serum betatrophin and FGF-21
      concentrations in women with polycystic ovary syndrome (PCOS). In this cross
      sectional study, we recruited 31 women with PCOS and 34 women as healthy
      controls. Serum betatrophin level and its relationship with serum FGF-21 level as
      well as metabolic parameters were examined. RESULTS: Serum betatrophin level was
      significantly higher in women with PCOS? than the control group [1.10 (0.20-4.20)
      vs 0.70 (0.20-3.50) ng/ml, p = 0.004], whereas FGF-21 did not differ between the
      groups [74.80 (7.80-435.90) vs 119.30 (10.50-443.40) pg/ml, p = 0.13]. Serum
      betatrophin correlated positively with LH levels (r = 0.26, p = 0.03). After
      controlling BMI, there was a significant positive correlation between betatrophin
      and FGF-21 (r = 0.25, p = 0.04). Multivariate regression analysis revealed that
      FGF-21 and presence of PCOS were the significant predictors of betatrophin
      concentrations (R2 = 0.22, F = 2.56, p = 0.03). CONCLUSIONS: Our results indicate
      that betatrophin levels are increased and associated with LH and FGF-21 levels,
      but not with insulin resistance, in women with PCOS.

PMID- 29363049
TI  - Beta-lactams in continuous infusion for Gram-negative bacilli osteoarticular
      infections: an easy method for clinical use.
AB  - : Continuous infusion (CI) of beta-lactams could optimize their
      pharmacokinetic/pharmacodynamic indices, especially in difficult-to-treat
      infections. PURPOSE: To validate an easy-to-use method to guide beta-lactams
      dosage in CI (formula). METHODS: A retrospective analysis was conducted of a
      prospectively collected cohort (n = 24 patients) with osteoarticular infections
      caused by Gram-negative bacilli (GNB) managed with beta-lactams in CI. Beta
      lactams dose was calculated using a described formula (daily dose = 24 h * beta
      lactam clearance * target "steady-state" concentration) to achieve concentrations
      above the MIC. We correlated the predicted concentration (Cpred = daily dose/24 h
      * beta-lactam clearance) with the patient's observed concentration (Cobs)
      measured by UPLC-MS/MS (Spearman's coefficient). RESULTS: The most frequent
      microorganism treated was P. aeruginosa (21 cases; 9 MDR). Beta-lactams in CI
      were ceftazidime (n = 14), aztreonam (7), and piperacillin/tazobactam (3), mainly
      used in combination (12 with colistin, 5 with ciprofloxacin) and administered
      without notable side effects. The plasma Cobs was higher overall than Cpred; the
      Spearman correlation between both concentrations was rho = 0.6 (IC 95%: 0.2-0.8)
      for all beta-lactams, and rho = 0.8 (IC 95%: 0.4-1) for those treated with
      ceftazidime. CONCLUSIONS: The formula may be useful in clinical practice for
      planning the initial dosage of beta-lactams in CI, while we await a systematic
      therapeutic drug monitoring. The use of beta-lactams in CI was safe.

PMID- 29363050
TI  - Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and
      Potential Implications for Maintenance Dose Optimisation in Future Clinical
      Trials.
AB  - BACKGROUND AND AIMS: In this study, we evaluate the performance of allometric
      concepts to predict the implications of age and size on the pharmacokinetics of
      lamotrigine, and assess the dose rationale across different age groups from 0.2
      to 91 years. METHODS: An allometrically scaled pharmacokinetic model was
      developed using adolescent and adult data, taking into account the effect of
      comedications. Model parameters were then used to extrapolate lamotrigine
      pharmacokinetics to older adults (> 65 years), children (4-12 years) and infants
      and toddlers (0.2-2.0 years). In addition, simulations were performed to identify
      the implication of different doses and dosing regimens for each population, so as
      to ensure steady-state concentrations within a predefined reference range.
      RESULTS: The pharmacokinetics of lamotrigine was best described using a one
      compartment model with first-order absorption and elimination. Carbamazepine,
      phenytoin, and valproic acid changed systemic clearance (CL) by + 76.5, + 129,
      and - 47.4%, respectively. Allometric principles allowed accurate extrapolation
      of disposition parameters to older adults and children older than 4 years of age.
      A maturation function was required to describe changes in exposure in younger
      patients. Compared with adults, a child aged 1.7 years has a 31.5% higher CL,
      after correcting for body weight. Patients > 65 years of age showed a decrease in
      CL of approximately 15%. CONCLUSION: Population pharmacokinetic models are
      usually limited to a subgroup of patients, which may mask the identification of
      factors contributing to interindividual variability. The availability of an
      integrated model including the whole patient population provides insight into the
      role of age-related changes in the disposition of lamotrigine, and potential
      implications for maintenance dose optimisation in any future trials. TRIAL
      REGISTRATION: According to GlaxoSmithKline's Clinical Trial Register, data from
      the GlaxoSmithKline studies LAM100034 and LEP103944, corresponding to
      ClinicalTrials.gov identifiers NCT00113165 and NCT00264615, used in this work,
      have been used in previous publications (doi:
      https://doi.org/10.1212/01.wnl.0000277698.33743.8b ,
      https://doi.org/10.1111/j.1528-1167.2007.01274.x ).

PMID- 29363051
TI  - Desiderata for digital consent in genomic research.
AB  - Herein, we describe the characterization of a Digital Consent (DC) System to
      support current ethical-legal issues associated with challenges posed by informed
      consent for genomic research. A potential solution to support ongoing interaction
      with patients and allow control over how their data and samples are being used in
      genomic research can be Digital Consent based. But there are other challenges
      that need to be addressed, such as incidental findings when analyzing the results
      of genomic tests (not expected). This paper addresses security and privacy
      recommendations for the development of precision medicine, and the
      interoperability references of Health Information Standardization Organizations
      such as HL7 and IHE, as well as recent research in the field of ethics in Genomic
      Medicine. As a result of this work, ten key features that need to be further
      explored have been identified in order to support the realization of DC in
      Genomic Research.

PMID- 29363052
TI  - Correction to: Beta2-Agonist Doping Control and Optical Isomer Challenges.
AB  - Page 1789, table 1, 'Carmoterol' row: The cell entry in the 'Stereochemistry'
      column, which previously read.

PMID- 29363053
TI  - Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle
      Injuries? A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Muscle lesions account for one-third of sport-related injuries, thus
      representing a substantial problem for both players and their teams. The use of
      platelet-rich plasma (PRP) injections is rapidly growing in clinical practice,
      prompted by an unmet clinical need with a large commercial market. However, after
      early reports of positive preliminary experience, higher quality studies recently
      questioned the real benefit provided by PRP injections to promote muscle healing
      and return to sport. OBJECTIVE: To evaluate the effect of platelet-rich plasma
      (PRP) injections on outcomes following acute muscle injuries. DESIGN: Meta
      analysis of randomized, controlled trials (RCTs), Level I. DATA SOURCES: PubMed
      (MEDLINE), Cochrane (CENTRAL), Web of Science, clinicaltrials.gov, who.int,
      isrctn.com, greylit.org, opengrey.eu. ELIGIBILITY CRITERIA: RCTs investigating
      the effect of PRP for the treatment of acute muscle injuries against at least one
      control group including patients treated with placebo injection or physical
      therapy. The outcomes evaluated were time to return to sport, re-injuries,
      complications, pain, muscle strength, range of motion (ROM)/flexibility, muscle
      function, and imaging. RESULTS: Six studies, involving 374 patients, were
      included in the meta-analysis. The time to return to sport evaluated in all six
      studies was significantly shorter in patients treated with PRP (mean difference =
      - 7.17 days). However, if only the double-blind studies (n = 2) or studies
      including only hamstring injuries (n = 3) were considered, non-significant
      differences were found. Re-injuries (relative risk = - 0.03) and complications
      (relative risk = 0.01) were also similar between the two groups (p > 0.05), nor
      were any substantial differences found regarding pain, muscle strength,
      ROM/flexibility, muscle function, and imaging. The performance bias was high risk
      due to the lack of patient blinding in four studies. The quality of evidence
      according to the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) was therefore low or very low. CONCLUSIONS: The promising
      biological rationale, the positive preclinical findings, and the successful early
      clinical experience of PRP injections are not confirmed by the recent high-level
      RCTs. Therefore any benefit in terms of pain, function, return to sport, and
      recurrence using PRP injections for the treatment of acute muscle injuries is not
      supported. Due to the bias in the studies, the heterogeneity of the findings, and
      the limited sample size, the evidence should be considered to be of low or very
      low quality.

PMID- 29363054
TI  - Nutritional and Environmental Influences on Athlete Health and Performance.

PMID- 29363055
TI  - Upper Respiratory Symptoms, Gut Health and Mucosal Immunity in Athletes.
AB  - Upper respiratory symptoms remain the most common illness in athletes. Upper
      respiratory symptoms during heavy training and competition may impair
      performance. Preventing illness is the primary reason for the use of supplements,
      such as probiotics and prebiotics, for maintaining or promoting gut health and
      immune function. While exercise-induced perturbations in the immune system may
      increase susceptibility to illness and infection, growing evidence indicates that
      upper respiratory symptoms are related to a breakdown in the homeostatic
      regulation of the mucosal immune system of the airways. Balancing protection of
      the respiratory tract with normal physiological functioning requires dynamic
      orchestration between a wide array of immune parameters. The intestinal
      microbiota regulates extra-intestinal immunity via the common mucosal immune
      system and new evidence implicates the microbiota of the nose, mouth and
      respiratory tract in upper respiratory symptoms. Omics' approaches now facilitate
      comprehensive profiling at the molecular and proteomic levels to reveal new
      pathways and molecules of immune regulation. New targets may provide for
      personalised nutritional and training interventions to maintain athlete health.

PMID- 29363056
TI  - Recombinant human maspin inhibits high glucose-induced oxidative stress and
      angiogenesis of human retinal microvascular endothelial cells via PI3K/AKT
      pathway.
AB  - Maspin is known as a tumor suppressor and a potent angiogenesis inhibitor,
      however, its effects on proliferative diabetic retinopathy (PDR) have not been
      fully elucidated. This study aimed at evaluating the effects of maspin on high
      glucose-induced oxidative stress and angiogenesis in human retinal microvascular
      endothelial cells (HRMECs). Herein, HRMECs were treated with 0.25, 0.5, or 1 uM
      recombinant human maspin in the presence of 30 mM glucose, and their
      proliferation, tube formation, and oxidative stress responses were further
      detected. Our results revealed that maspin inhibited the high glucose-induced
      proliferation, migration, and tube formation of HRMECs. Maspin also decreased
      reactive oxygen species, nitric oxide level, and increased glutathione S
      transferase activity in HRMECs. Meanwhile, maspin reduced the mRNA and protein
      levels of hypoxia-inducible factor-1alpha and vascular endothelial growth factor
      in high glucose-stimulated cells in a dose-dependent manner. Additionally, the
      high glucose-induced elevation of phosphorylated phosphoinositide-3-kinase (p
      PI3K) and phosphorylated AKT was also suppressed by maspin. In summary, our data
      suggest that maspin inhibits high glucose-induced proliferation, oxidative
      stress, and angiogenesis of HRMECs at least by modulating the PI3K/AKT pathway.
      Maspin may be a potential therapeutic agent for the prevention and treatment of
      PDR.

PMID- 29363057
TI  - Ameliorative effects of supplemental folinic acid on Lamotrigine-induced fetal
      malformations in the mouse.
AB  - Data from our previous work indicate that Lamotrigine (LTG) is teratogenic in the
      mouse. In the present study, we attempted to determine the possible protective
      effects of exogenous folate on LTG-induced fetal anomalies in TO mouse.
      Experiment I entailed administering 4 mg/kg of folinic acid (FA) and (25 mg/kg)
      of LTG intraperitoneally three times on gestation day (GD) 8 to a group of mice;
      other groups were a group that received similar volumes of saline, a group that
      received LTG and Saline, a group that received FA and saline. Experiment 2
      involved administering groups of mice with daily 3 doses FA (or proportionate
      volume of saline) on GD 5 through 10 and either 3 doses of saline on GD8, or 3
      doses of LTG on GD8. Maternal plasma concentrations of FA, vitamin B12 and
      homocysteine were determined an hour after the last injection from one-half of
      all animals. The other half were allowed to go to term (GD18) when they were
      euthanized and their fetuses were examined for visceral and skeletal
      malformations. A high incidence of resorption, abortion, embryolethality,
      congenital malformations, and intrauterine growth restriction (IUGR), was
      observed in the LTG-treated group. Folic acid and B12 levels were decreased and
      homocysteine concentration increased significantly in LTG groups. Mice receiving
      LTG with FA had normal levels of folate, Vitamin B12 and homocysteine levels, and
      the fetuses had fewer birth defects similar to the controls which were given
      saline only. Supplemental FA ameliorated to a great extent the LTG-induced
      embryonic resorption and malformations and restored the FA status.

PMID- 29363058
TI  - Role of the beta3-adrenergic receptor subtype in catecholamine-induced myocardial
      remodeling.
AB  - beta3-Adrenoceptors (AR) stimulate cardiac Na+/K+ pump in healthy hearts. beta3
      ARs are upregulated by persistent sympathetic hyperactivity; however, their
      effect on Na+/K+ ATPase activity and ventricular function in this condition is
      still unknown. Here, we investigate preventive effects of additional beta3-AR
      activation (BRL) on Na+/K+ ATPase activity and in vivo hemodynamics in a model of
      noradrenaline-induced hypertrophy. Rats received NA or NA plus simultaneously
      administered BRL in vivo infusion for 14 days; their cardiac function was
      investigated by left ventricular pressure-volume analysis. Moreover, fibrosis and
      apoptosis were also assessed histologically. NA induced an hypertrophic pattern,
      as detected by morphological, histological, and biochemical markers. Additional
      BRL exposure reversed the hypertrophic pattern and restored Na+/K+ ATPase
      activity. NA treatment increased systolic function and depressed diastolic
      function (slowed relaxation). Additional BRL treatment reversed most NA-induced
      hemodynamic changes. NA decreased Na+/K+ pump alpha2 subunit expression
      selectively, a change also reversed by additional BRL treatment. Increasing beta3
      AR stimulation may prevent the consequences of chronic NA exposure on Na+/K+ pump
      and in vivo hemodynamics. beta3-AR agonism may thus represent a new therapeutic
      strategy for pharmacological modulation of hypertrophy under conditions of
      chronically enhanced sympathetic activity.

PMID- 29363059
TI  - Berberine activates bitter taste responses of enteroendocrine STC-1 cells.
AB  - Glucagon-like peptide-1 (GLP-1) is involved in the regulation of insulin
      secretion and glucose homeostasis. GLP-1 release is stimulated when berberine
      interacts with a novel G protein family (TAS2Rs) in enteroendocrine cells. In
      this study, we used STC-1 cells and examined a marked increase in Ca2+ in
      response to various bitter compounds. Ca2+ responses to traditional Chinese
      medicine extracts, including berberine, phellodendrine and coptisine, in STC-1
      cells were suppressed by the phospholipase C (PLC) inhibitor U-73122, suggesting
      the involvement of bitter taste receptors in changing the physiological status of
      enteroendocrine cells in a PLC-dependent manner. STC-1 cells showed berberine-up
      regulated preproglucagon (GLP-1 precursor) mRNA and GLP-1 secretion. A QPCR
      analysis demonstrated that TAS2R38, a subtype of the bitter taste receptor, was
      associated with GLP-1 secretion. Berberine-mediated GLP-1 secretion was
      attenuated in response to small interfering RNA silencing of TAS2R38. The current
      studies demonstrated that Galpha-gustducin co-localized with GLP-1 and Tas2r106
      in the STC-1 cells. We further utilized inhibitors of PLC and TRPM5, which are
      known to participate in taste signal transduction, to investigate the underlying
      pathways mediated in berberine-induced GLP-1 secretion. Berberine-induced GLP-1
      release from enteroendocrine cells is modulated in a PLC-dependent manner through
      a process involving the activation of bitter taste receptors. Together, our data
      demonstrated a berberine-mediated GLP-1 secretion pathway in mouse
      enteroendocrine cells that could be of therapeutic relevance to hyperglycemia and
      the role of bitter taste receptors in the function of the small intestine.

PMID- 29363061
TI  - Social effects on reference frame selection.
AB  - The presence of another person in a spatial scene has been shown to induce
      spontaneous perspective taking. This investigation presents two experiments
      exploring whether the presence of another person affects reference frame
      selection when representing object locations in memory. Participants studied
      objects from one view and later performed judgments of relative direction, which
      tested retrieval of the remembered layout from several imagined perspectives.
      Without another person in the scene during learning, participants selected a
      reference frame aligned with the studied view. The mere presence of the
      experimenter at a different perspective during learning did not affect reference
      frame selection. Requiring participants to process object locations from the
      experimenter's view during learning led to the selection of a reference frame
      aligned with the experimenter. However, the same effect also occurred when
      participants processed object locations from the perspective of a wooden box. In
      sum, the presence of another person during learning did not affect reference
      frame selection, and participants adopted a nonegocentric reference frame whether
      the nonegocentric perspective was occupied by a person or an object.

PMID- 29363062
TI  - Metabolomics as a Tool to Understand Pathophysiological Processes.
AB  - Multiple diseases have a strong metabolic component, and metabolomics as a
      powerful phenotyping technology, in combination with orthogonal biological and
      clinical approaches, will undoubtedly play a determinant role in accelerating the
      understanding of mechanisms that underlie these complex diseases determined by a
      set of genetic, lifestyle, and environmental exposure factors. Here, we provide
      several examples of valuable findings from metabolomics-led studies in diabetes
      and obesity metabolism, neurodegenerative disorders, and cancer metabolism and
      offer a longer term vision toward personalized approach to medicine, from
      population-based studies to pharmacometabolomics.

PMID- 29363063
TI  - Metabolomics in Immunology Research.
AB  - There is a growing appreciation that metabolic processes and individual
      metabolites can shape the function of immune cells and thereby play important
      roles in the outcome of immune responses. In this respect, the use of MS- and NMR
      spectroscopy-based platforms to characterize and quantify metabolites in
      biological samples has recently yielded important novel insights into how our
      immune system functions and has contributed to the identification of biomarkers
      for immune-mediated diseases. Here, these recent immunological studies in which
      metabolomics has been used and made significant contributions to these fields
      will be discussed. In particular the role of metabolomics to the rapidly
      advancing field of cellular immunometabolism will be highlighted as well as the
      future prospects of such metabolomic tools in immunology.

PMID- 29363060
TI  - Inflammation, oxidative stress, and higher expression levels of Nrf2 and NQO1
      proteins in the airways of women chronically exposed to biomass fuel smoke.
AB  - The study was carried out to examine whether chronic exposure to smoke during
      daily household cooking with biomass fuel (BMF) elicits changes in airway
      cytology and expressions of Nrf2 (nuclear factor erythroid 2 [NF-E2]-related
      factor 2 [Nrf2]), Keap1 (Kelch-like erythroid-cell-derived protein with CNC
      homology [ECH]-associated protein 1), and NQO1 (NAD(P)H:quinone oxidoreductase 1)
      proteins in the airways. For this, 282 BMF-using women (median age 34 year) and
      236 age-matched women who cooked with liquefied petroleum gas (LPG) were
      enrolled. Particulate matter with diameters of < 10 um (PM10) and < 2.5 um
      (PM2.5) were measured in indoor air with real-time laser photometer. Routine
      hematology, sputum cytology, Nrf2, Keap1, NQO1, and generation of reactive oxygen
      species (ROS) along with the levels of superoxide dismutase (SOD) and catalase
      were measured in both groups. PM10 and PM2.5 levels were significantly higher in
      BMF-using households compared to LPG. Compared with LPG users, BMF users had 32%
      more leukocytes in circulation and their sputa were 1.4-times more cellular with
      significant increase in absolute number of neutrophils, lymphocytes, eosinophils,
      and alveolar macrophages, suggesting airway inflammation. ROS generation was 1.5
      times higher in blood neutrophils and 34% higher in sputum cells of BMF users
      while erythrocyte SOD was 31% lower and plasma catalase was relatively unchanged,
      suggesting oxidative stress. In BMF users, Keap1 expression was reduced, the
      percentage of AEC with nuclear expression of Nrf2 was two- to three-times more,
      and NQO1 level in sputum cell lysate was two-times higher than that of LPG users.
      In conclusion, cooking with BMF was associated with Nrf2 activation and elevated
      NQO1 protein level in the airways. The changes may be adaptive cellular response
      to counteract biomass smoke-elicited oxidative stress and inflammation-related
      tissue injury in the airways.

PMID- 29363064
TI  - LC-MS-Based Metabolomics of Biofluids Using All-Ion Fragmentation (AIF)
      Acquisition.
AB  - The field of liquid chromatography-mass spectrometry (LC-MS)-based nontargeted
      metabolomics has advanced significantly and can provide information on thousands
      of compounds in biological samples. However, compound identification remains a
      major challenge, which is crucial in interpreting the biological function of
      metabolites. Herein, we present a LC-MS method using the all-ion fragmentation
      (AIF) approach in combination with a data processing method using an in-house
      spectral library. For the purposes of increasing accuracy in metabolite
      annotation, up to four criteria are used: (1) accurate mass, (2) retention time,
      (3) MS/MS fragments, and (4) product/precursor ion ratios. The relative standard
      deviation between ion ratios of a metabolite in a biofluid vs. its analytical
      standard is used as an additional metric for confirming metabolite identity.
      Furthermore, we include a scheme to distinguish co-eluting isobaric compounds.
      Our method enables database-dependent targeted as well as nontargeted
      metabolomics analysis from the same data acquisition, while simultaneously
      improving the accuracy in metabolite identification to increase the quality of
      the resulting biological information.

PMID- 29363065
TI  - Lipid Mediator Metabolomics Via LC-MS/MS Profiling and Analysis.
AB  - Solid-phase extraction coupled with liquid chromatography tandem mass
      spectrometry provides a robust and sensitive approach for the identification and
      quantitation of specialized pro-resolving mediators (lipoxins, resolvins,
      protectins, and maresins), their pathway markers and the classic eicosanoids.
      Here, we provide a detailed description of the methodologies employed for the
      extraction of these mediators from biological systems, setup of the
      instrumentation, sample processing, and then the procedures followed for their
      identification and quantitation.

PMID- 29363066
TI  - UHPSFC/ESI-MS Analysis of Lipids.
AB  - This new analytical approach for high-throughput and comprehensive lipidomic
      analysis of biological samples using ultrahigh-performance supercritical fluid
      chromatography (UHPSFC) with electrospray ionization-mass spectrometry (ESI-MS)
      is based on lipid class separation using 1.7 MUm particle bridged ethylene hybrid
      silica columns and a gradient of methanol-water-ammonium acetate mixture as a
      modifier. The method enables a fast separation of 30 nonpolar and polar lipid
      classes within 6-min analysis time covering six main lipid categories including
      fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterols, and
      prenols. Individual lipid species within lipid classes are identified based on
      positive- and negative-ion full scan and tandem mass spectra measured with high
      mass accuracy and high resolving power. The method is used for the quantitative
      analysis of lipid species in biological tissues using internal standards for each
      lipid class. This high-throughput, comprehensive, and accurate UHPSFC/ESI-MS
      method is suitable for the lipidomic analysis of large sample sets in clinical
      research.

PMID- 29363067
TI  - LC-MS/MS Analysis of Lipid Oxidation Products in Blood and Tissue Samples.
AB  - Oxygenated lipid products of non-cyclooxygenase derivatives, namely, prostanoids
      such as, isoprostanes and isofurans, are formed in vivo through lipid
      autoxidation. Insofar it has been marked as novel biomarkers of oxidative stress
      in the biological systems. Elevations of these oxidized products are associated
      with several diseases. This chapter describes the preparation and measurement of
      the products, including newly identified F2-dihomo-isoprostanes and dihomo
      isofurans, from plasma and tissue samples using the liquid chromatography-tandem
      mass spectrometry approach.

PMID- 29363068
TI  - Serum Testosterone by Liquid Chromatography Tandem Mass Spectrometry for Routine
      Clinical Diagnostics.
AB  - In clinical diagnostics, samples containing low testosterone cannot be analyzed
      by random access immunoassays normally available at clinical laboratories. For
      these samples, sensitive and specific LC-MS/MS-based testosterone methods are
      required. An LC-MS/MS-based testosterone assay is described that was developed
      and validated for routine clinical application.

PMID- 29363069
TI  - LC-MS/MS Analysis of Bile Acids.
AB  - Besides their role as lipid solubilizers, bile acids (BAs) are increasingly
      appreciated as bioactive molecules. They bind to G-protein-coupled receptors and
      nuclear hormone receptors. So they control their own metabolism and act on lipid
      and energy metabolism. Here we describe a simple, accurate, and fast liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification
      of BAs in human plasma/serum.

PMID- 29363070
TI  - LC-MS/MS Analysis of Triglycerides in Blood-Derived Samples.
AB  - The increasing interest in the analysis of triglyceride (TG) species and the
      individual fatty acid (FA) composition requires expeditious and reliable
      quantification strategies. The utilization of flow injection analysis (FIA)
      coupled to quadrupole tandem mass spectrometry (MS/MS) for the simultaneous
      quantitation of TG and identification of FA composition facilitates the
      multiplexed verification of various biomarkers from small sample quantities.
      Enzymatic methods based on saponification and glycerol analysis are not suited
      for the determination of the FA distribution in TGs. This protocol proposes a
      procedure for the establishment of a relative quantitation method for middle- to
      high-abundance plasma TGs and the corresponding FA composition. Essential topics
      as FIA-MS/MS method development as well as sample preparation and validation
      strategies are described in detail.

PMID- 29363071
TI  - LC-MS/MS Analysis of the Epoxides and Diols Derived from the Endocannabinoid
      Arachidonoyl Ethanolamide.
AB  - Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a useful tool to
      characterize the behavior of natural lipids within biological matrices. We report
      a LC-MS/MS method developed specifically to analyze CYP products of the
      arachidonoyl ethanolamide (anandamide, AEA), the epoxyeicosatrienoic acid
      ethanolamides (EET-EAs) and their hydrolyzed metabolites, and the
      dihydroxyeicosatrienoic acid ethanolamides (DHET-EAs). This method was used to
      measure EET-EA biotransformation to DHET-EAs by two human epoxide hydrolases: the
      soluble EH (sEH) and the microsomal EH (mEH). In general, sEH and mEH substrate
      preference was similar, based on kcat/KM. The 14,15-EET-EA and 11,12-EET-EA were
      the most efficiently hydrolyzed, followed by 8,9-EET-EA and 5,6-EET-EA. The
      method was also used to detect endogenous levels of these lipids in mouse
      tissues, although levels were below the instrumental detection limit (0.1-3.4
      nM). Because both AEA and EETs are biologically active, the method described
      herein will be invaluable in revealing the role(s) of EET-EAs in vivo.

PMID- 29363072
TI  - Sphingolipid Analysis in Clinical Research.
AB  - Sphingolipids are the most diverse class of lipids due to the numerous variations
      in their structural components. This diversity is also reflected in their
      extremely different functions. Sphingolipids are not only constituents of cell
      membranes but have also emerged as key signaling molecules involved in a variety
      of cellular functions, such as cell growth and differentiation, proliferation,
      and apoptotic cell death. Lipidomic analyses in clinical research have identified
      pathways and products of sphingolipid metabolism that are altered in several
      human pathologies. In this article, we describe how to properly design a
      lipidomic experiment in clinical research, how to handle plasma and serum samples
      for this purpose, and how to measure sphingolipids using liquid chromatography
      mass spectrometry.

PMID- 29363073
TI  - Shotgun Lipidomics Approach for Clinical Samples.
AB  - Shotgun lipidomics offers fast and reproducible identification and quantification
      of lipids in clinical samples. Lipid extraction procedures based on the methyl
      tert-butyl protocol are well established for performing shotgun lipidomics in
      biomedical research. Here, we describe a shotgun lipidomics workflow that is well
      suited for the analysis of clinical samples such as tissue samples, blood plasma,
      and peripheral blood mononuclear cells.

PMID- 29363074
TI  - Establishing and Performing Targeted Multi-residue Analysis for Lipid Mediators
      and Fatty Acids in Small Clinical Plasma Samples.
AB  - LC-MS/MS- and GC-MS-based targeted metabolomics is typically conducted by
      analyzing and quantifying a cascade of metabolites with methods specifically
      developed for the metabolite class. Here we describe an approach for the
      development of multi-residue analytical profiles, calibration standards, and
      internal standard solutions in support of a fast, simple, and low-cost plasma
      sample preparation that captures and quantitates a range of metabolite cascades.

PMID- 29363075
TI  - Chemical Isotope Labeling LC-MS for Human Blood Metabolome Analysis.
AB  - Blood is a widely used biofluid in discovery metabolomic research to search for
      clinical metabolite biomarkers of diseases. Analyzing the entire human blood
      metabolome is a major analytical challenge, as blood, after being processed into
      serum or plasma, contains thousands of metabolites with diverse chemical and
      physical properties as well as a wide range of concentrations. We describe an
      enabling method based on high-performance chemical isotope labeling (CIL) liquid
      chromatography-mass spectrometry (LC-MS) for in-depth quantification of the
      metabolomic differences in comparative blood samples with high accuracy and
      precision.

PMID- 29363076
TI  - Direct Infusion-Tandem Mass Spectrometry (DI-MS/MS) Analysis of Complex Lipids in
      Human Plasma and Serum Using the LipidyzerTM Platform.
AB  - Lipids play a key role in the signaling pathways of cancer, cardiovascular,
      diabetic, and inflammatory diseases. A major challenge in the analysis of lipids
      is the many isobaric interferences present in highly complex samples that
      confound identification and accurate quantitation. After obtaining the total
      lipid extract from a sample, differential mobility separation has proven to be a
      powerful tool for gas-phase fractionation of lipid classes. When combined with
      mass spectrometry, this allows the unambiguous identification and thus
      quantification of lipid molecular species. These components, sample extraction,
      gas-phase separation, and mass spectrometry, form the basis of a novel integrated
      quantitative lipid analysis platform.

PMID- 29363077
TI  - Exploratory GC/MS-Based Metabolomics of Body Fluids.
AB  - GC/MS-based metabolomics is a powerful tool for metabolic phenotyping and
      biomarker discovery from body biofluids. In this chapter, we describe an
      untargeted metabolomic approach for plasma/serum and fecal water sample
      profiling. It describes a multistep procedure, from sample preparation,
      oximation/silylation derivatization, and data acquisition using GC/QToF to data
      processing consisting in data extraction and identification of metabolites.

PMID- 29363078
TI  - GC-MS Analysis of Short-Chain Fatty Acids in Feces, Cecum Content, and Blood
      Samples.
AB  - Short-chain fatty acids, the end products of fermentation of dietary fibers by
      the gut microbiota, have been shown to exert multiple effects on mammalian
      metabolism. For the analysis of short-chain fatty acids, gas chromatography-mass
      spectrometry is a very powerful and reliable method. Here, we describe a fast,
      reliable, and reproducible method for the separation and quantification of short
      chain fatty acids in mouse feces, cecum content, and blood samples (i.e., plasma
      or serum) using gas chromatography-mass spectrometry. The short-chain fatty acids
      analyzed include acetic acid, propionic acid, butyric acid, valeric acid,
      hexanoic acid, and heptanoic acid.

PMID- 29363079
TI  - GC-MS Analysis of Medium- and Long-Chain Fatty Acids in Blood Samples.
AB  - Our body contains a wide variety of fatty acids that differ in chain length, the
      degree of unsaturation, and location of the double bonds. As the various fatty
      acids play distinct roles in health and disease, methods that can specifically
      determine the fatty acid profile are needed for fundamental and clinical studies.
      Here we describe a method for the separation and quantification of fatty acids
      ranging from 8 to 24 carbon chain lengths in blood samples using gas
      chromatography-mass spectrometry following derivatization using pentafluorobenzyl
      bromide. This method quantitatively monitors fatty acid composition in a manner
      that satisfies the requirements for comprehensiveness, sensitivity, and accuracy.

PMID- 29363080
TI  - Analysis of Oxysterols.
AB  - Oxysterols are oxygenated derivatives of cholesterol formed in the human body or
      ingested in the diet. By modulating the activity of many proteins (for instance,
      liver X receptors, oxysterol-binding proteins, some ATP-binding cassette
      transporters), oxysterols can affect many cellular functions and influence
      various physiological processes (e.g., cholesterol metabolism, membrane fluidity
      regulation, intracellular signaling pathways). Due to their crucial role, it is
      important to be able to quantify them in pathological conditions. The method
      described here permits to measure the content of oxysterol in plasma, cell, or
      media using GC-MS.

PMID- 29363081
TI  - Analysis of Metabolites from the Tricarboxylic Acid Cycle for Yeast and Bacteria
      Samples Using Gas Chromatography Mass Spectrometry.
AB  - We here explain step by step the implementation of gas chromatography coupled
      with tandem mass spectrometry for the quantitative analysis of intracellular
      metabolites from the tricarboxylic acid (TCA) cycle such as citrate, isocitrate,
      alpha-ketoglutarate, succinate, malate, and fumarate. Isotope dilution is used to
      correct for potential metabolite losses during sample processing, matrix effects,
      incomplete derivatization, and liner contamination. All measurements are
      performed in selected reaction monitoring (SRM) mode. Standards and samples are
      first diluted with a fixed volume of a mixture of fully 13 C-labeled internal
      standards and then derivatized to give trimethylsilyl-methoxylamine derivatives
      prior GC-MS/MS analysis.

PMID- 29363082
TI  - GC-MS Analysis of Lipid Oxidation Products in Blood, Urine, and Tissue Samples.
AB  - Oxidant stress has been identified as important in the pathology of many
      diseases. Oxidation products of polyunsaturated fatty acids collectively termed
      isoprostanes, neuroprostanes, and isofurans are considered the most reliable
      measures of in vivo lipid oxidation, and they are widely used to assess oxidant
      stress in various diseases. Here we describe the measurement of these lipid
      oxidation products using gas chromatography mass spectrometry with electron
      capture negative ionization.

PMID- 29363083
TI  - Metabolic Profiling of Urine by Capillary Electrophoresis-Mass Spectrometry Using
      Non-covalently Coated Capillaries.
AB  - In the field of metabolomics, capillary electrophoresis-mass spectrometry (CE-MS)
      can be considered a very useful analytical tool for the profiling of polar and
      charged metabolites. However, variability of migration time is an important issue
      in CE. An elegant way to minimize this problem is the use of non-covalently
      coated capillaries that is dynamic coating of the bare fused-silica capillary
      with solutions of charged polymers. In this protocol, an improved strategy for
      the profiling of cationic metabolites in urine by CE-MS using multilayered non
      covalent capillary coatings is presented. Capillaries are coated with a bilayer
      of polybrene (PB) and poly(vinyl sulfonate) (PVS) or with a triple layer of PB,
      dextran sulfate (DS), and PB. The bilayer- and triple-layer-coated capillaries
      have a negative and positive outside layer, respectively. It is shown that the
      use of such capillaries provides very repeatable migration times.

PMID- 29363084
TI  - CE-MS for the Analysis of Amino Acids.
AB  - Amino acids play an important role in clinical analysis. Capillary
      electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) has proven
      to possess several characteristics that make it a powerful and useful tool for
      the analysis of amino acids in clinical studies. Here we present a method for the
      separation and quantitative analysis of 27 amino acids in urine based on CE-ESI
      MS. The method presents an improved resolution between the isomers Leu, Ile, and
      aIle, in comparison to other CE-ESI-MS methods in the literature. This method is
      fast, selective, and simple and has improved sensitivity by applying a pH
      mediated stacking strategy, showing that it can be successfully used for amino
      acid analysis and probably for other small cationic metabolites.

PMID- 29363085
TI  - NMR Analysis of Fecal Samples.
AB  - Fecal analysis can generate data that is relevant for the exploration of gut
      microbiota and their relationship with the host. Nuclear magnetic resonance (NMR)
      spectroscopy is an excellent tool for the profiling of fecal extracts as it
      enables the simultaneous detection of various metabolites from a broad range of
      chemical classes including, among others, short-chain fatty acids, organic acids,
      amino acids, bile acids, carbohydrates, amines, and alcohols. Compounds present
      at low MUM concentrations can be detected and quantified with a single
      measurement. Moreover, NMR-based profiling requires a relatively simple sample
      preparation. Here we describe the three main steps of the general workflow for
      the NMR-based profiling of feces: sample preparation, NMR data acquisition, and
      data analysis.

PMID- 29363086
TI  - Quantitative Analysis of Central Energy Metabolism in Cell Culture Samples.
AB  - Nuclear magnetic resonance (NMR) is one of the key analytical platforms used in
      the analysis of intracellular and extracellular metabolites. Despite the
      technological advances that allow for the production of high-quality data, the
      sampling procedures of cultured cells are less well standardized. Different cell
      lines and culture media composition require adjustments of the protocols to
      result meaningful quantitative information. Here we provide the workflow for
      obtaining quantitative metabolic data from adherent mammalian cells using NMR
      spectroscopy. The robustness of NMR allows for the implementation of the here
      described protocol to other cell types with only minor adjustments.

PMID- 29363087
TI  - Mass Spectrometry Imaging of Metabolites.
AB  - Mass spectrometry imaging (MSI) is a technique which is gaining increasing
      interest in biomedical research due to its capacity to visualize molecules in
      tissues. First applied to the field of clinical proteomics, its potential for
      metabolite imaging in biomedical studies is now being recognized. Here we
      describe how to set up experiments for mass spectrometry imaging of metabolites
      in clinical tissues and how to tackle most of the obstacles in the subsequent
      analysis of the data.

PMID- 29363088
TI  - Quality-Assured Biobanking: The Leiden University Medical Center Model.
AB  - Prospective or "de novo" biobanking is becoming increasingly popular. Biobanks
      are installed to provide large collections of biological materials for future
      medical research. Quality assurance of biobank samples is an important aspect of
      biobanking. Therefore, it is vital that all samples are collected and processed
      in a similar manner according to standardized procedures to ensure high-quality
      samples and reduce variability in the analytical process. We describe the
      processes of the centralized biobanking facility at the Leiden University Medical
      Center (LUMC).

PMID- 29363089
TI  - Extracting Knowledge from MS Clinical Metabolomic Data: Processing and Analysis
      Strategies.
AB  - Assessing potential alterations of metabolic pathways using large-scale
      approaches today plays a central role in clinical research. Because several
      thousands of mass features can be measured for each sample with separation
      techniques hyphenated to mass spectrometry (MS) detection, adapted strategies
      should be implemented to detect altered pathways and help to elucidate the
      mechanisms of pathologies. These procedures include peak detection, sample
      alignment, normalization, statistical analysis, and metabolite annotation.
      Interestingly, considerable advances have been made over the last years in terms
      of analytics, bioinformatics, and chemometrics to help massive and complex
      metabolomic data to be more adequately handled with automated processing and data
      analysis workflows. Recent developments and remaining challenges related to MS
      signal processing, metabolite annotation, and biomarker discovery based on
      statistical models are illustrated in this chapter considering their application
      to clinical research.

PMID- 29363090
TI  - Elevated Aromatase (CYP19A1) Expression Is Associated with a Poor Survival of
      Patients with Estrogen Receptor Positive Breast Cancer.
AB  - Genetic variants in CYP19A1, the gene encoding aromatase, have been reported to
      be associated with circulating estrogen concentrations, a key risk factor for
      breast cancer. The mechanism underlying this association is still unclear; it has
      been suggested that some of these variants may alter the expression and/or
      activity of aromatase. Here we analyzed the expression of intra-tumoral CYP19A1
      messenger RNA (mRNA) and the genotypes of rs10046, a well-characterized single
      nucleotide polymorphism in CYP19A1, in 138 breast cancer patients and 15 breast
      cancer cell lines. The genotype TT was detected in 36 patients and six cell
      lines, genotype CT in 55 patients and five cell lines, and genotype CC in 28
      patients and four cell lines. We found no evidence for a significant association
      of CYP19A1 levels with rs10046 genotypes, although expression tended to be higher
      in tumors and cell lines with the homozygous risk genotype TT. We also found no
      evidence for a significant association of rs10046 genotypes with breast cancer
      prognosis. In contrast, high CYP19A1 expression was highly significantly
      associated with a poor overall, disease-free, and metastasis-free survival in
      estrogen receptor-positive but not negative breast cancer patients. Moreover,
      CYP19A1 mRNA was significantly elevated in postmenopausal patients and in
      patients older than 50 years, and a trend towards a positive correlation with ER
      status and ESR1 mRNA expression was observed. These findings highlight the key
      role of aromatase in estrogen receptor-positive breast cancer biology.

PMID- 29363092
TI  - The tolerability of Potassium Citrate Tablet in patients with intolerance to
      Potassium Citrate Powder form.
AB  - PURPOSE: To assess the tolerability of Potassium Citrate (KCit) tablet in
      patients with kidney stones that were not able to use the powder form of this
      drug due to unfavorable salty taste and gastrointestinal complications. MATERIALS
      AND METHODS: Twenty-three stone formers, with intolerance to potassium citrate
      powder form, which had referred to Labbafinejad stone preventive clinic (2015),
      have been included in this study. All of the patients took two Potassium citrate
      tablets (10 meq), three times a day for two weeks. Spot urine sample and the 24
      hour urine collections were performed before and after KCit therapy. In addition,
      a visual analog taste scale was completed to gauge the taste and palatability of
      the KCit tablet in comparing with the powder form. RESULTS: All of the patients
      claimed that they consumed the tablets as prescribed. The urine pH and the 24
      hour citrate and potassium were significantly higher after the treatment. In
      addition, the mean visual analog scale score was significantly improved in KCit
      therapy with tablet form versus to powder type (good vs. terrible score).
      CONCLUSION: Oral tolerance of KCit therapy is improved with the use of Potassium
      Citrate tablet, with beneficial effects on 24-hour urine citrate, potassium, and
      pH.

PMID- 29363091
TI  - Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor
      Progression in Rats.
AB  - Use of drug combinations that target different pathways involved in the
      development and progression of prostate cancer (PCa) has emerged as an
      alternative to overcome the resistance caused by drug monotherapies. The
      antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235)
      may be suitable options for the prevention of drug resistance and the inhibition
      of PCa progression. The aim of the present study was to evaluate whether
      abiraterone acetate and BEZ235 achieve superior therapeutic effects to either
      drug administered as monotherapy, in the early stages of PCa in an androgen
      dependent system. Our study showed that each drug might impair tumor growth by
      reducing proliferation and increasing cell death when administered as
      monotherapy. However, tumor growth continued to progress with each drug
      monotherapy and some important side effects were related to BEZ. Conversely, when
      used in combination, the drugs impaired the inflammatory response, decreased
      hyperplastic lesions, and blocked tumor progression from premalignant to a
      malignant stage. Our data showed that the strategy to block the androgenic and
      PI3K/AKT/mTOR pathway is an effective therapeutic option and should be
      investigated including distinct PI3K pathway inhibitors.

PMID- 29363093
TI  - A prospective 52-week randomized controlled trial of patient-initiated care
      consultations for patients with psoriasis.
AB  - BACKGROUND: Treatment and care of moderate-to-severe psoriasis require lifelong
      consultations with a dermatologist with close monitoring of systemic treatment.
      OBJECTIVES: To investigate the effect of patient-initiated care consultation
      (PICC) for patients with psoriasis in a dermatology outpatient clinic. METHODS: A
      prospective randomized controlled trial with patients on well-controlled systemic
      treatment randomized to either (i) the PICC group, where they participated in one
      annual consultation with a dermatologist but were able to initiate consultations
      when needed; or (ii) routine care, where they participated in a consultation
      every 12-16 weeks. The primary outcome was the Dermatology Life Quality Index
      (DLQI). Other outcomes were safety, patient adherence and satisfaction with
      healthcare assessed at baseline and after 52 weeks. The study was registered with
      clinical trials number NCT02382081. RESULTS: In total 150 patients were included,
      with 58.0% treated with biologics, 37.3% with methotrexate and 4.7% with
      acitretin. At week 52 no statistically significant mean difference between groups
      was detected in DLQI (0.28, 95% confidence interval -0.35 to 0.9) or Psoriasis
      Area and Severity Index (-0.24, 95% confidence interval -0.84 to 0.36). Patients
      in the PICC group requested 63% fewer consultations with a dermatologist: mean
      2.5 +/- 0.1 vs. 5.1 +/- 0.6 (P = 0.001). Patient adherence and safety with
      treatment monitoring were equal between groups, but the PICC group was
      significantly better at attending consultations than the control group (P =
      0.003). CONCLUSIONS: PICC offers additional clinical benefits over routine care,
      making patients less dependent on clinical visits. The intervention adds no harm
      to monitoring systemic treatment, and patients report high quality of life and
      satisfaction with healthcare.

PMID- 29363094
TI  - A brief comment about predictive models for mortality in intensive care units.

PMID- 29363095
TI  - Hydration prevents chronic hyperglycaemic patients from neurological
      deterioration post-ischaemic stroke.
AB  - OBJECTIVES: To determine whether chronic hyperglycaemia predisposes patients to
      dehydration, which may promote neurological deterioration, and to investigate
      whether dehydration control improves functional outcome. PATIENTS AND METHODS:
      This study included 355 patients hospitalized with acute ischaemic stroke and
      diabetes mellitus who fulfilled the glycaemic gap <=0. We used the following cut
      offs: (i) no chronic hyperglycaemia (glycated haemoglobin A1c [HbA1c] < 7%) and
      (ii) chronic hyperglycaemia (HbA1c >= 7%). The chronic hyperglycaemic patients
      were randomly divided into the control group and the hydration group. Hydration
      therapy was only initiated in the hydration group. The blood urea nitrogen
      (BUN)/creatinine (Cr) ratio was used as an indicator of dehydration. Stroke
      severity on admission and discharge was assessed by means of National Institutes
      of Health Stroke Scale (NIHSS). RESULTS: The mean baseline BUN/Cr ratios were
      higher in the control group and hydration group than in the no chronic
      hyperglycaemia group. The mean BUN/Cr ratio decreased from 91.22 +/- 29.95 on the
      first day to 77.03 +/- 18.23 on the third day (P < .001) in the hydration group.
      On the third day after admission, there was no significant difference in the
      BUN/Cr ratio between the hydration group and the no chronic hyperglycaemia group
      (P = .831). Moreover, neurological deterioration was highest in the control group
      (33.6%, 36/107), followed by the hydration group (10.5%, 11/105) and the no
      chronic hyperglycaemia group (5.6%, 8/143). CONCLUSIONS: Chronic hyperglycaemia
      was associated with the admission NIHSS score and neurological deterioration
      after excluding the effect of stress hyperglycaemia. Furthermore, hydration
      therapy may help prevent neurological deterioration.

PMID- 29363097
TI  - A good pilot to navigate troubled waters.

PMID- 29363096
TI  - Electroclinical findings and long-term outcomes in epileptic patients with inv
      dup (15).
AB  - OBJECTIVE: To define the electroclinical phenotype and long-term outcomes in a
      cohort of patients with inv dup (15) syndrome. MATERIAL AND METHODS: The
      electroclinical data of 45 patients (25 males) affected by inv dup (15) and
      seizures were retrospectively analysed, and long-term follow-up of epilepsy was
      evaluated. RESULTS: Epilepsy onset was marked by generalized seizures in 53% of
      patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in
      11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized
      epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic
      spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug
      resistant epilepsy was detected in 55.5% of patients. There was a significant
      higher prevalence of seizure-free patients in those with seizure onset after the
      age of 5 years and with focal epilepsy, with respect to those with earlier
      epilepsy onset because most of these later developed an epileptic encephalopathy
      (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact,
      among patients with early-onset epilepsy, those presenting with epileptic spasms
      as the only seizure type associated with classical hypsarrhythmia achieved
      seizure freedom (P < .001) compared to patients with spasms and other seizure
      types associated with modified hypsarrhythmia. CONCLUSIONS: Epilepsy in inv dup
      (15) leads to a more severe burden of disease. Frequently, these patients show
      drug resistance, in particular when epilepsy onset is before the age of five and
      features epileptic encephalopathy.

PMID- 29363098
TI  - Infants born preterm, stress, and neurodevelopment in the neonatal intensive care
      unit: might music have an impact?
AB  - AIM: The neonatal intensive care unit (NICU) provides life-saving medical care
      for an increasing number of newborn infants each year. NICU care, while
      lifesaving, does have attendant consequences which can include repeated
      activation of the stress response and reduced maternal interaction, with possible
      negative long-term impacts on brain development. Here we present a
      neuroscientific framework for considering the impact of music on neurodevelopment
      in the NICU of infants born preterm and evaluate current literature on the use of
      music with this population to determine what is most reliably known of the
      physiological effects of music interventions. METHOD: Using online academic
      databases we collected relevant, experimental studies aimed at determining
      effects of music listening in infants in the NICU. These articles were evaluated
      for methodological rigor, ranking the 10 most experimentally stringent as a
      representative sample. RESULTS: The selected literature seems to indicate that
      effects are present on the cardio-pulmonary system and behavior of neonates,
      although the relative effect size remains unclear. INTERPRETATION: These findings
      indicate a need for more standardized longitudinal studies aimed at determining
      not only whether NICU music exposure has beneficial effects on the cardio
      pulmonary system, but also on the hypothalamic-pituitary-adrenal axis, brain
      structures, and cognitive behavioral status of these children as well. WHAT THIS
      PAPER ADDS: Provides a neuroscience framework for considering how music might
      attenuate stress in neonatal intensive care unit (NICU) infants. Considers how
      repeated stress may cause negative neurodevelopmental impacts in infants born
      preterm. Posits epigenetics can serve as a mechanistic pathway for music
      moderating the stress response.

PMID- 29363099
TI  - Hidradenitis suppurativa, a review of pathogenesis, associations and management.
      Part 2.
AB  - Hidradenitis suppurativa is a chronic, painful, autoinflammatory condition
      resulting in nodules, abscesses and sinus tracts. We present an evidence-based
      review providing new understanding of the pathogenesis of hidradenitis
      suppurativa and associated comorbidities. By the nature of their speciality,
      dermatologists are uniquely positioned to investigate and treat patients.

PMID- 29363100
TI  - Non-transport emergency medical service missions - a retrospective study based on
      medical charts.
AB  - BACKGROUND: In Finland, approximately 40% of emergency medical service (EMS)
      missions do not result in transport of the patient to a hospital by ambulance,
      and there is wide variability in the reasons underlying non-transport decisions.
      The aim of this study was to describe the context of these EMS non-transport
      missions. METHODS: The data were collected retrospectively between 3 September
      and 20 October 2014 by investigating non-transport EMS charts (n = 1154). Event
      information and patients' main symptoms were extracted from information found in
      EMS charts and quantified using content and statistical analyses. RESULTS:
      Patients' need for EMS were explained by various reasons. One-third of the
      missions were caused by organ-specific symptoms, whereas in 30.8% of cases the
      reason for EMS was unspecified. Sudden onset symptoms were noted for 38.4% of the
      cases, whereas in 14.7% of cases the symptoms had persisted for days or weeks
      before EMS contact. EMS personnel offered guidance instead of treatment in 79.2%
      of the missions. CONCLUSIONS: Non-transport missions represent a significant
      daily work load for the EMS. Although most of the symptoms showed acute onset,
      the majority of these missions involved only assessment of medical necessity
      and/or guidance without any medical treatment. It is questionable whether this
      use of the EMS is cost-effective for any healthcare system.

PMID- 29363101
TI  - Acute brain lesions on magnetic resonance imaging in relation to neurological
      outcome after cardiac arrest.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of the brain including diffusion
      weighted imaging (DWI) is reported to have high prognostic accuracy in
      unconscious post-cardiac arrest (CA) patients. We documented acute MRI findings
      in the brain in both conscious and unconscious post-CA patients treated with
      target temperature management (TTM) at 32-34 degrees C for 24 h as well as the
      relation to patients' neurological outcome after 6 months. METHODS: A prospective
      observational study with MRI was performed regardless of the level of
      consciousness in post-CA patients treated with TTM. Neurological outcome was
      assessed using the Cerebral Performance Categories scale and dichotomized into
      good and poor outcome. RESULTS: Forty-six patients underwent MRI at 3-5 days post
      CA. Patients with good outcome had minor, mainly frontal and parietal, lesions.
      Acute hypoxic/ischemic lesions on MRI including DWI were more common in patients
      with poor outcome (P = 0.007). These lesions affected mostly gray matter (deep or
      cortical), with or without involvement of the underlying white matter. Lesions in
      the occipital and temporal lobes, deep gray matter and cerebellum showed
      strongest associations with poor outcome. Decreased apparent diffusion
      coefficient, was more common in patients with poor outcome. CONCLUSIONS:
      Extensive acute hypoxic/ischemic MRI lesions in the cortical regions, deep gray
      matter and cerebellum detected by visual analysis as well as low apparent
      diffusion coefficient values from quantitative measurements were associated with
      poor outcome. Patients with good outcome had minor hypoxic/ischemic changes,
      mainly in the frontal and parietal lobes.

PMID- 29363102
TI  - Mitochondrial DNA Heteroplasmy and Purifying Selection in the Mammalian Female
      Germ Line.
AB  - Inherited mutations in the mitochondrial (mt)DNA are a major cause of human
      disease, with approximately 1 in 5000 people affected by one of the hundreds of
      identified pathogenic mtDNA point mutations or deletions. Due to the severe, and
      often untreatable, symptoms of many mitochondrial diseases, identifying how these
      mutations are inherited from one generation to the next has been an area of
      intense research in recent years. Despite large advances in our understanding of
      this complex process, many questions remain unanswered, with one of the most
      hotly debated being whether or not purifying selection acts against pathogenic
      mutations during germline development.

PMID- 29363103
TI  - Effect of combined epidural anaesthesia on tumor-infiltrating lymphocytes in lung
      adenocarcinoma: a prospective exploratory sub-analysis.
AB  - BACKGROUND: Regional anaesthesia may have advantages in preserving immune
      function. Tumor-infiltrating lymphocytes (TILs) are considered indicators of
      immune response in the tumor microenvironment and used as a prognostic marker in
      patients after cancer surgery. This study investigated the effects of combined
      epidural anaesthesia on the number of TILs in patients undergoing surgery for
      lung adenocarcinoma. METHODS: Patients undergoing radical resection for primary
      lung cancer were randomized to receive either combined epidural-general
      anaesthesia (Epi-GA) or general anaesthesia (GA) in an ongoing randomized
      controlled trial (ChiCTR-TRC-14004136). Excised adenocarcinoma specimens from
      patients enrolled between 1 June 2015 and 30 November 2015 were selected for
      immunohistochemical staining of CD8 and FOXP3 molecules. The numbers of positive
      lymphocytes were counted and expressed as the number of cells per mm2 tumor area.
      RESULTS: One hundred and twenty-eight patients were recruited and randomized; 64
      patients were included in immunohistochemistry analysis (37 received Epi-GA vs.
      27 received GA). The number of CD8+ T cells was higher in the Epi-GA group than
      in the GA group (median [interquartile range]: 292.8 [198.0-418.3] vs. 204.7
      [131.1-305.8], P = 0.036); whereas the number of FOXP3+ T cells was less in the
      Epi-GA group than in the GA group (37.6 [14.7-92.3] vs. 99.8 [68.9-168.3], P <
      0.001). CONCLUSIONS: For patients undergoing surgery for lung adenocarcinoma
      under general anesthesia, use of epidural anaesthesia increased CD8+ T cells
      infiltration but decreased FOXP3+ T cells accumulation in tumor tissues. Epidural
      anaesthesia may affect TILs in a manner that preserves immune function.

PMID- 29363104
TI  - Bridge flap repair for central nasal dorsum defect.
AB  - Surgery of the nose to remove skin cancer often requires the use of local flaps.
      We present a defect after the extirpation of a previously incompletely excised
      infiltrative squamous cell carcinoma, which we repaired with a Bridge flap, a
      bipedicled and subcutaneous islanded flap whose excellent vascularity allows
      reliable reconstruction and rapid mobilisation, with dependable results.

PMID- 29363105
TI  - Anticoagulation for the initial treatment of venous thromboembolism in people
      with cancer.
AB  - BACKGROUND: Compared with people without cancer, people with cancer who receive
      anticoagulant treatment for venous thromboembolism (VTE) are more likely to
      develop recurrent VTE. OBJECTIVES: To compare the efficacy and safety of three
      types of parenteral anticoagulants (i.e. fixed-dose low molecular weight heparin
      (LMWH), adjusted-dose unfractionated heparin (UFH), and fondaparinux) for the
      initial treatment of VTE in people with cancer. SEARCH METHODS: A comprehensive
      search included a major electronic search of the following databases: Cochrane
      Central Register of Controlled Trials (CENTRAL) (2018, Issue 1), MEDLINE (via
      Ovid) and Embase (via Ovid); handsearching of conference proceedings; checking of
      references of included studies; use of the 'related citation' feature in PubMed;
      and a search for ongoing studies. This update of the systematic review was based
      on the findings of a literature search conducted on 14 January 2018. SELECTION
      CRITERIA: Randomized controlled trials (RCTs) assessing the benefits and harms of
      LMWH, UFH, and fondaparinux in people with cancer and objectively confirmed VTE.
      DATA COLLECTION AND ANALYSIS: Using a standardized form, we extracted data in
      duplicate on study design, participants, interventions outcomes of interest, and
      risk of bias. Outcomes of interested included all-cause mortality, symptomatic
      VTE, major bleeding, minor bleeding, postphlebitic syndrome, quality of life, and
      thrombocytopenia. We assessed the certainty of evidence for each outcome using
      the GRADE approach. MAIN RESULTS: Of 15440 identified citations, 7387 unique
      citations, 15 RCTs fulfilled the eligibility criteria. These trials enrolled 1615
      participants with cancer and VTE: 13 compared LMWH with UFH enrolling 1025
      participants, one compared fondaparinux with UFH and LMWH enrolling 477
      participants, and one compared dalteparin with tinzaparin enrolling 113
      participants. The meta-analysis of mortality at three months included 418
      participants from five studies and that of recurrent VTE included 422
      participants from 3 studies. The findings showed that LMWH likely decreases
      mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence
      interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101
      fewer to 17 more; moderate certainty evidence), but did not rule out a clinically
      significant increase or decrease in VTE recurrence (RR 0.69, 95% CI 0.27 to 1.76;
      RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; moderate certainty
      evidence).The study comparing fondaparinux with heparin (UFH or LMWH) did not
      exclude a beneficial or detrimental effect of fondaparinux on mortality at three
      months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139
      more; moderate certainty evidence), recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54;
      RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; moderate certainty evidence),
      major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40
      fewer to 44 more; moderate certainty evidence), or minor bleeding (RR 1.53, 95%
      CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate
      certainty evidence)The study comparing dalteparin with tinzaparin did not exclude
      a beneficial or detrimental effect of dalteparin on mortality (RR 0.86, 95% CI
      0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty
      evidence), recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95%
      CI 77 fewer to 98 more; low certainty evidence), major bleeding (RR 2.19, 95% CI
      0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty
      evidence), or minor bleeding (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000,
      95% CI 95 fewer to 164 more; low certainty evidence). AUTHORS' CONCLUSIONS: LMWH
      is possibly superior to UFH in the initial treatment of VTE in people with
      cancer. Additional trials focusing on patient-important outcomes will further
      inform the questions addressed in this review. The decision for a person with
      cancer to start LMWH therapy should balance the benefits and harms and consider
      the person's values and preferences.

PMID- 29363106
TI  - Factors Associated with Hospital Admission after Outpatient Surgery in the
      Veterans Health Administration.
AB  - OBJECTIVE: To examine factors associated with 0- to 7-day admission after
      outpatient surgery in high-volume specialties: general surgery, orthopedics,
      urology, ear/nose/throat, and podiatry. STUDY DESIGN: We calculated rates and
      assessed diagnosis codes for 0- to 7-day admission after outpatient surgery for
      Centers for Medicare and Medicaid Services (CMS) and Veterans Health
      Administration (VA) dually enrolled patients age 65 and older. We also estimated
      separate multilevel logistic regression models to compare patient, procedure, and
      facility characteristics associated with postoperative admission. DATA
      COLLECTION: 2011-2013 surgical encounter data from the VA Corporate Data
      Warehouse; geographic data from the Area Health Resources File; CMS enrollment
      and hospital admission data. PRINCIPAL FINDINGS: Among 63,585 outpatient
      surgeries in 124 facilities, 0- to 7-day admission rates ranged from 5 percent
      (podiatry) to 28 percent (urology); nearly 66 percent of the admissions occurred
      on the day of surgery. Only 97 admissions were detected in the CMS data (1
      percent). Surgical complications were diagnosed in 4 percent of admissions.
      Procedure complexity, measured by relative value units or anesthesia risk score,
      was associated with admission across all specialties. CONCLUSION: As many as 20
      percent of VA outpatient surgeries result in an admission. Complex procedures are
      more likely to be followed by admission, but more evidence is required to
      determine how many of these reflect potential safety or quality problems.

PMID- 29363107
TI  - Identifying co-opted transposable elements using comparative epigenomics.
AB  - The human genome gives rise to different epigenomic landscapes that define each
      cell type and can be deregulated in disease. Recent efforts by ENCODE, the NIH
      Roadmap and the International Human Epigenome Consortium (IHEC) have made
      significant advances towards assembling reference epigenomic maps of various
      tissues. Notably, these projects have found that approximately 80% of human DNA
      was biochemically active in at least one epigenomic assay while only
      approximately 10% of the sequence displayed signs of purifying selection. Given
      that transposable elements (TEs) make up at least 50% of the human genome and can
      be actively transcribed or act as regulatory elements either for their own
      purposes or be co-opted for the benefit of their host; we are interested in
      exploring their overall contribution to the "functional" genome. Traditional
      methods used to identify functional DNA have relied on comparative genomics,
      conservation analysis and low throughput validation assays. To discover co-opted
      TEs, and distinguish them from noisy genomic elements, we argue that comparative
      epigenomic methods will also be important.

PMID- 29363108
TI  - Can Exercise Improve Cognitive Symptoms of Alzheimer's Disease?
AB  - OBJECTIVES: To examine the effects of exercise training on cognitive function in
      individuals at risk of or diagnosed with Alzheimer's disease (AD). DESIGN: Meta
      analysis. SETTING: PubMed, Scopus, ClinicalTrials.gov, and ProQuest were searched
      from inception until August 1, 2017. PARTICIPANTS: Nineteen studies with 23
      interventions including 1,145 subjects with a mean age of 77.0 +/- 7.5 were
      included. Most subjects were at risk of AD because they had mild cognitive
      impairment (64%) or a parent diagnosed with AD (1%), and 35% presented with AD.
      INTERVENTION: Controlled studies that included an exercise-only intervention and
      a nondiet, nonexercise control group and reported pre- and post-intervention
      cognitive function measurements. MEASUREMENTS: Cognitive function before and
      after the intervention and features of the exercise intervention. RESULTS:
      Exercise interventions were performed 3.4 +/- 1.4 days per week at moderate
      intensity (3.7 +/- 0.6 metabolic equivalents) for 45.2 +/- 17.0 minutes per
      session for 18.6 +/- 10.0 weeks and consisted primarily of aerobic exercise
      (65%). Overall, there was a modest favorable effect of exercise on cognitive
      function (d+  = 0.47, 95% confidence interval (CI) = 0.26-0.68). Within-group
      analyses revealed that exercise improved cognitive function (d+w  = 0.20, 95% CI 
      = 0.11-0.28), whereas cognitive function declined in the control group (d+w  = 
      0.18, 95% CI  = -0.36 to 0.00). Aerobic exercise had a moderate favorable effect
      on cognitive function (d+w  = 0.65, 95% CI = 0.35-0.95), but other exercise types
      did not (d+w  = 0.19, 95% CI = -0.06-0.43). CONCLUSION: Our findings suggest that
      exercise training may delay the decline in cognitive function that occurs in
      individuals who are at risk of or have AD, with aerobic exercise possibly having
      the most favorable effect. Additional randomized controlled clinical trials that
      include objective measurements of cognitive function are needed to confirm our
      findings.

PMID- 29363109
TI  - Inhibition of SLC1A5 sensitizes colorectal cancer to cetuximab.
AB  - Cetuximab resistance is a key barrier in treating metastatic colorectal cancer
      (mCRC). Targeting of metabolic resources import could resensitize drug-resistant
      cancer cells to anticancer treatments. Here we showed that the expression of the
      glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC
      samples of patients resisted to cetuximab was significantly higher than in those
      of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene
      silencing or pharmacological inhibitor significantly suppressed the growth of
      CRC. Moreover, inhibition of SLC1A5 significantly enhanced the inhibitory
      efficacy of cetuximab on CRC proliferation both in vitro and in vivo.
      Mechanistically, SLC1A5 inhibition facilitated EGFR degradation through the
      ubiquitin-proteasome pathway, and decreased the expression of nuclear EGFR, both
      of which might have contribution to the improved response to cetuximab. This
      study provides the metabolic molecule SLC1A5 as a potential therapeutic target to
      increase the efficacy of cetuximab on CRC.

PMID- 29363110
TI  - Women's Sexual Health and Aging.
AB  - Older women are often sexually active, but physicians caring for older women
      rarely address sexual concerns. Although women's desire for sex declines with
      age, a majority of older women rate sex as having importance in their lives.
      Women identify emotional intimacy as an important reason for engaging in sexual
      relationships. Women are less likely than men to have an available spousal or
      intimate partner and more likely to have a partner with sexual difficulties of
      their own. Up to half of sexually active older women report a distressing sexual
      problem, with low desire and problems related to genitourinary syndrome
      (vulvovaginal atrophy) being most common. Difficulty with orgasm in older women
      is often associated with a partner's erectile dysfunction. Sexually transmitted
      infections (STIs) are increasingly prevalent in older women. A minority of older
      women report discussing sexual issues with a physician. Most commonly, the
      patient initiates discussions. Physicians should ask regularly and proactively
      about sexual activity and function. Important interventions include offering
      practical advice to common chronic medical conditions and sexual problems that
      confront older women; treating vulvovaginal atrophy; and providing STI screening,
      prevention strategies, and treatment when appropriate.

PMID- 29363111
TI  - Demography and selection shape transcriptomic divergence in field crickets.
AB  - Gene flow, demography, and selection can result in similar patterns of genomic
      variation and disentangling their effects is key to understanding speciation.
      Here, we assess transcriptomic variation to unravel the evolutionary history of
      Gryllus rubens and Gryllus texensis, cryptic field cricket species with highly
      divergent mating behavior. We infer their demographic history and screen their
      transcriptomes for footprints of selection in the context of the inferred
      demography. We find strong support for a long history of bidirectional gene flow,
      which ceased during the late Pleistocene, and a bottleneck in G. rubens
      consistent with a peripatric origin of this species. Importantly, the demographic
      history has likely strongly shaped patterns of genetic differentiation (empirical
      FST distribution). Concordantly, FST -based selection detection uncovers a large
      number of outliers, likely comprising many false positives, echoing recent
      theoretical insights. Alternative genetic signatures of positive selection,
      informed by the demographic history of the sibling species, highlighted a smaller
      set of loci; many of these are candidates for controlling variation in mating
      behavior. Our results underscore the importance of demography in shaping overall
      patterns of genetic divergence and highlight that examining both demography and
      selection facilitates a more complete understanding of genetic divergence during
      speciation.

PMID- 29363112
TI  - Anatomical network analysis of the musculoskeletal system reveals integration
      loss and parcellation boost during the fins-to-limbs transition.
AB  - Tetrapods evolved from within the lobe-finned fishes around 370 Ma. The evolution
      of limbs from lobe-fins entailed a major reorganization of the skeletal and
      muscular anatomy of appendages in early tetrapods. Concurrently, a degree of
      similarity between pectoral and pelvic appendages also evolved. Here, we compared
      the anatomy of appendages in extant lobe-finned fishes (Latimeria and
      Neoceratodus) and anatomically plesiomorphic amphibians (Ambystoma, Salamandra)
      and amniotes (Sphenodon) to trace and reconstruct the musculoskeletal changes
      that took place during the fins-to-limbs transition. We quantified the anatomy of
      appendages using network analysis. First, we built network models-in which nodes
      represent bones and muscles, and links represent their anatomical connections-and
      then we measured network parameters related to their anatomical integration,
      heterogeneity, and modularity. Our results reveal an evolutionary transition
      toward less integrated, more modular appendages. We interpret this transition as
      a diversification of muscle functions in tetrapods compared to lobe-finned
      fishes. Limbs and lobe-fins show also a greater similarity between their pectoral
      and pelvic appendages than ray-fins do. These findings on extant species provide
      a basis for future quantitative and comprehensive reconstructions of the anatomy
      of limbs in early tetrapod fossils, and a way to better understand the fins-to
      limbs transition.

PMID- 29363113
TI  - Socioeconomic status and diagnosis, treatment, and mortality in men with prostate
      cancer. Nationwide population-based study.
AB  - Patients with high socioeconomic status (SES) have better cancer outcomes than
      patients with low SES. This has also been shown in Sweden, a country with tax
      financed health care aiming to provide care on equal terms to all residents. The
      association between income and educational level and diagnostics and treatment as
      outlined in national guidelines and prostate cancer (Pca) and all-cause mortality
      was assessed in 74,643 men by use of data in the National Prostate Cancer
      Register of Sweden and a number of other health care registers and demographic
      databases. In multivariable logistic regression analysis, men with high income
      had higher probability of Pca detected in a health-check-up, top versus bottom
      income quartile, odds ratio (OR) 1.60 (95% CI 1.45-1.77) and lower probability of
      waiting more than 3 months for prostatectomy, OR 0.77 (0.69-0.86). Men with the
      highest incomes also had higher probability of curative treatment for
      intermediate and high-risk cancer, OR 1.77 (1.61-1.95) and lower risk of positive
      margins, (incomplete resection) at prostatectomy, OR 0.80 (0.71-0.90). Similar,
      but weaker associations were observed for educational level. At 6 years of follow
      up, Pca mortality was modestly lower for men with high income, which was
      statistically significant for localized high-risk and metastatic Pca in men with
      no comorbidities. All-cause mortality was less than half in top versus bottom
      quartile of income (12% vs. 30%, p < 0.001) among men above age 65. Our findings
      underscore the importance of adherence to guidelines to ensure optimal and equal
      care for all patients diagnosed with cancer.

PMID- 29363114
TI  - Exome sequencing and case-control analyses identify RCC1 as a candidate breast
      cancer susceptibility gene.
AB  - Breast cancer is a genetic disease but the known genes explain a minority of
      cases. To elucidate the molecular basis of breast cancer in the Tunisian
      population, we performed exome sequencing on six BRCA1/BRCA2 mutation-negative
      patients with familial breast cancer and identified a novel frameshift mutation
      in RCC1, encoding the Regulator of Chromosome Condensation 1. Subsequent
      genotyping detected the 19-bp deletion in additional 5 out of 153 (3%) breast
      cancer patients but in none of 400 female controls (p = 0.0015). The deletion was
      enriched in patients with a positive family history (5%, p = 0.0009) and co
      segregated with breast cancer in the initial pedigree. The mutant allele was lost
      in 4/6 breast tumors from mutation carriers which may be consistent with the
      hypothesis that RCC1 dysfunction provides a selective disadvantage at the stage
      of tumor progression. In summary, we propose RCC1 as a likely breast cancer
      susceptibility gene in the Tunisian population.

PMID- 29363115
TI  - Do terrorist attacks affect ethnic discrimination in the labour market? Evidence
      from two randomized field experiments.
AB  - Terrorist attacks are known to influence public opinion. But do they also change
      behaviour? We address this question by comparing the results of two identical
      randomized field experiments on ethnic discrimination in hiring that we conducted
      in Oslo. The first experiment was conducted before the 2011 terrorist attacks in
      Norway; the second experiment was conducted after the attacks. In both
      experiments, applicants with a typical Pakistani name were significantly less
      likely to get a job interview compared to those with a typical Norwegian name.
      But the ethnic gap in call-back rates were very similar in the two experiments.
      Thus, Pakistanis in Norway still experienced the same level of discrimination,
      despite claims that Norwegians have become more positive about migrants after the
      far-right, anti-migrant terrorist attacks of 2011.

PMID- 29363118
TI  - Promoting oral health through fluoride: Adopted by the FDI General Assembly:
      August 2017, Madrid, Spain.

PMID- 29363117
TI  - Serotonin receptor 1A promoter polymorphism, rs6295, modulates human anxiety
      levels via altering parasympathetic nervous activity.
AB  - OBJECTIVE: The G-allele of the -1019C/G (rs6295) promoter polymorphism of the
      serotonin receptor 1A (HTR1A) gene has been implicated in anxiety; however, the
      underlying neurophysiological processes are still not fully understood. Recent
      evidence indicates that low parasympathetic (vagal) tone is predictive of
      anxiety. We thus conducted a structural equation model (SEM) to examine whether
      the HTR1A rs6295 variant can affect anxiety by altering parasympathetic nervous
      activity. METHOD: A sample of 1141 drug-free healthy Han Chinese was recruited
      for HTR1A genotyping. Autonomic nervous function was assessed by short-term
      spectral analysis of heart rate variability (HRV). Anxiety and stress levels were
      evaluated by the Beck Anxiety Inventory (BAI) and the Perceived Stress Scale
      (PSS) respectively. RESULTS: The number of the HTR1A G allele was inversely
      correlated with high-frequency power (HF), a parasympathetic index of HRV. The HF
      index was negatively associated with BAI scores. Furthermore, the good-fitting
      SEM, adjusting for confounding variables (e.g., age and PSS levels), revealed a
      significant pathway linking rs6295 variant to BAI scores via HF index modulation.
      CONCLUSION: These results are the first to show that HTR1A -1019C/G polymorphism
      influences anxiety levels by modulating parasympathetic tone, providing a
      neurophysiological insight into the role of HTR1A in human anxiety.

PMID- 29363116
TI  - EML4-ALK fusion variant V3 is a high-risk feature conferring accelerated
      metastatic spread, early treatment failure and worse overall survival in ALK+ non
      small cell lung cancer.
AB  - In order to identify anaplastic lymphoma kinase-driven non-small cell lung cancer
      (ALK+ NSCLC) patients with a worse outcome, who might require alternative
      therapeutic approaches, we retrospectively analyzed all stage IV cases treated at
      our institutions with one of the main echinoderm microtubule-associated protein
      like 4 (EML4)-ALK fusion variants V1, V2 and V3 as detected by next-generation
      sequencing or reverse transcription-polymerase chain reaction (n = 67).
      Progression under tyrosine kinase inhibitor (TKI) treatment was evaluated both
      according to Response Evaluation Criteria in Solid Tumors (RECIST) and by the
      need to change systemic therapy. EML4-ALK fusion variants V1, V2 and V3 were
      found in 39%, 10% and 51% of cases, respectively. Patients with V3-driven tumors
      had more metastatic sites at diagnosis than cases with the V1 and V2 variants
      (mean 3.3 vs. 1.9 and 1.6, p = 0.005), which suggests increased disease
      aggressiveness. Furthermore, V3-positive status was associated with earlier
      failure after treatment with first and second-generation ALK TKI (median
      progression-free survival [PFS] by RECIST in the first line 7.3 vs. 39.3 months,
      p = 0.01), platinum-based combination chemotherapy (median PFS 5.4 vs. 15.2
      months for the first line, p = 0.008) and cerebral radiotherapy (median brain PFS
      6.1 months vs. not reached for cerebral radiotherapy during first-line treatment,
      p = 0.028), and with inferior overall survival (39.8 vs. 59.6 months in median, p
      = 0.017). Thus, EML4-ALK fusion variant V3 is a high-risk feature for ALK+ NSCLC.
      Determination of V3 status should be considered as part of the initial workup for
      this entity in order to select patients for more aggressive surveillance and
      treatment strategies.

PMID- 29363119
TI  - Dental Practice and Third Parties: Adopted by the General Assembly: August 2017,
      Madrid, Spain.

PMID- 29363120
TI  - Sustainability in Dentistry: Adopted by the FDI General Assembly: August 2017,
      Madrid, Spain.

PMID- 29363122
TI  - Odontogenic Pain Management: Adopted by the FDI General Assembly: August 2017,
      Madrid, Spain.

PMID- 29363121
TI  - Lifelong Oral Health: Adopted by the FDI General Assembly: August 2017, Madrid,
      Spain.

PMID- 29363123
TI  - 2017 FDI policy statements.

PMID- 29363125
TI  - Quality in Dentistry: Adopted by the FDI General Assembly: August 2017, Madrid,
      Spain.

PMID- 29363124
TI  - Continuing Dental Education: Adopted by the FDI General Assembly: August 2017,
      Madrid, Spain.

PMID- 29363126
TI  - CAD/CAM Dentistry: Adopted by the FDI General Assembly: August 2017, Madrid,
      Spain.

PMID- 29363127
TI  - Advertising in Dentistry: Adopted by the FDI General Assembly: August 2017,
      Madrid, Spain.

PMID- 29363128
TI  - Poor family functioning mediates the link between childhood adversity and
      adolescent nonsuicidal self-injury.
AB  - BACKGROUND: Non-suicidal self-injury (NSSI) is a common harmful behavior during
      adolescence. Exposure to childhood family adversity (CFA) is associated with
      subsequent emergence of NSSI during adolescence. However, the pathways through
      which this early environmental risk may operate are not clear. AIMS: We tested
      four alternative hypotheses to explain the association between CFA and adolescent
      onset NSSI. METHODS: A community sample of n = 933 fourteen year olds with no
      history of NSSI were followed up for 3 years. RESULTS: Poor family functioning at
      age 14 mediated the association between CFA before age 5 and subsequent onset of
      NSSI between 14 and 17 years. CONCLUSIONS: The findings support the cumulative
      suboptimal environmental hazards (proximal family relationships as a mediator)
      hypothesis. Improving the family environment at age 14 may mitigate the effects
      of CFA on adolescent onset of NSSI.

PMID- 29363129
TI  - Developmental patterns and variation among early theropods.
AB  - Understanding ontogenetic patterns is important in vertebrate paleontology
      because the assessed skeletal maturity of an individual often has implications
      for paleobiogeography, species synonymy, paleobiology, and body size evolution of
      major clades. Further, for many groups the only means of confidently determining
      ontogenetic status of an organism is through the destructive process of
      histological sampling. Although the ontogenetic patterns of Late Jurassic and
      Cretaceous dinosaurs are better understood, knowledge of the ontogeny of the
      earliest dinosaurs is relatively poor because most species-level growth series
      known from these groups are small (usually, maximum of n ~ 5) and incomplete. To
      investigate the morphological changes that occur during ontogeny in early
      dinosaurs, I used ontogenetic sequence analysis (OSA) to reconstruct
      developmental sequences of morphological changes in the postcranial ontogeny of
      the early theropods Coelophysis bauri and Megapnosaurus rhodesiensis, both of
      which are known from large sample sizes (n = 174 and 182, respectively). I found
      a large amount of sequence polymorphism (i.e. intraspecific variation in
      developmental patterns) in both taxa, and especially in C. bauri, which possesses
      this variation in every element analyzed. Megapnosaurus rhodesiensis is similar,
      but it possesses no variation in the sequence of development of ontogenetic
      characters in the tibia and tarsus. Despite the large amount of variation in
      development, many characters occur consistently earlier or later in ontogeny and
      could therefore be important morphological features for assessing the relative
      maturity of other early theropods. Additionally, there is a phylogenetic signal
      to the order in which homologous characters appear in ontogeny, with homologous
      characters appearing earlier or later in developmental sequences of early
      theropods and the close relatives of dinosaurs, silesaurids. Many of these
      morphological features are important characters for the reconstruction of
      archosaurian phylogeny (e.g. trochanteric shelf). Because these features vary in
      presence or appearance with ontogeny, these characters should be used with
      caution when undertaking phylogenetic analyses in these groups, since a specimen
      may possess certain character states owing to ontogenetic stage, not evolutionary
      relationships.

PMID- 29363130
TI  - A new species of Petroleuciscus (Teleostei: Cyprinidae) from the Buyuk Menderes
      River, southwestern Anatolia, Turkey.
AB  - Petroleuciscus ninae sp. nov. is described from the Buyuk Menderes River
      drainage. The new species is distinguished by having a black lateral stripe from
      head to base of caudal fin, stripe distinct anteriorly and posteriorly, wider
      than eye diameter; numerous black pigments on anal-fin rays; body depth at dorsal
      fin origin 27-30% standard length (LS ); head width at posterior margin of eye 16
      19% LS ; and eye diameter smaller than snout length. Petroleuciscus ninae is also
      distinguished from other species in adjacent waters by having six fixed
      diagnostic nucleotide substitutions in the mitochondrial DNA coI barcode region.

PMID- 29363131
TI  - Differentiation and classification of thoracolumbar transitional vertebrae.
AB  - The literature states that transitional vertebrae at any junction are
      characterized by features retained from two adjacent regions in the vertebral
      column. Currently, there is no published literature available that describes the
      prevalence or morphology of thoracolumbar transitional vertebrae (TLTV). The aim
      of this study was to identify the qualitative characteristics of transitional
      vertebrae at the thoracolumbar junction and establish a technique to
      differentiate the various subtypes that may be found. A selection of vertebral
      columns from skeletal remains (n = 35) were evaluated in this study. Vertebrae
      were taken based on features that are atypical for vertebrae in each relative
      region. The transitional vertebrae were qualitatively identified based on
      overlapping thoracic and lumbar features of vertebrae at the thoracolumbar
      junction. The following general overlapping characteristics were observed:
      aplasia or hypoplasia of the transverse process, irregular orientation on the
      superior articular process and atypical mammillary bodies. The results show that
      the most frequent location of the transitional vertebrae was in the thoracic
      region (f = 23). The second most frequent location was in the lumbar region (f =
      10). In two specimens of the selection (f = 2), an additional 13th thoracic
      vertebra was present which functioned as a transitional vertebra. This study
      concluded that one can accurately identify the characteristics of transitional
      vertebrae at the thoracolumbar junction. In addition, the various subtypes can be
      differentiated according to the region in the vertebral column the vertebra is
      located in and the relative number of vertebral segments in the adjacent regions
      of the vertebral column. This provides a qualitative tool for researchers to
      differentiate the transitional vertebrae from distinctly different typical
      thoracic or lumbar vertebrae at the thoracolumbar junction.

PMID- 29363132
TI  - Revealing the 'obscurin': mapping the path to new discovery with the
      phosphoproteome.

PMID- 29363133
TI  - Effect of food shortage and temperature on age 0+ salmonids: a contribution to
      predict the effects of climate change.
AB  - Brown trout Salmo trutta alevins were maintained at 8 and 11 degrees  C at three
      conditions over a 9 day period from yolk sac exhaustion: fed ad libitum, starved
      or fed ad libitum after starvation. Whole-body gene expressions for proteins
      involved in energy metabolism and the two primary proteolytic pathways were
      assessed. This study is the first to show an over-expression of proteasome and
      autophagy-related genes in young stages of salmonids, particularly at 11 degrees 
      C.

PMID- 29363134
TI  - The net acid extruders NHE1, NBCn1 and MCT4 promote mammary tumor growth through
      distinct but overlapping mechanisms.
AB  - High metabolic and proliferative rates in cancer cells lead to production of
      large amounts of H+ and CO2 , and as a result, net acid extruding transporters
      are essential for the function and survival of cancer cells. We assessed protein
      expression of the Na+ /H+ exchanger NHE1, the Na+ - HCO3- cotransporter NBCn1,
      and the lactate-H+ cotransporters MCT1 and -4 by immunohistochemical analysis of
      a large cohort of breast cancer samples. We found robust expression of these
      transporters in 20, 10, 4 and 11% of samples, respectively. NHE1 and NBCn1
      expression both correlated positively with progesterone receptor status, NHE1
      correlated negatively and NBCn1 positively with HER2 status, whereas MCT4
      expression correlated with lymph node status. Stable shRNA-mediated knockdown
      (KD) of either NHE1 or NBCn1 in the MDA-MB-231 triple-negative breast cancer
      (TNBC) cell line significantly reduced steady-state intracellular pH (pHi ) and
      capacity for pHi recovery after an acid load. Importantly, KD of any of the three
      transporters reduced in vivo primary tumor growth of MDA-MB-231 xenografts.
      However, whereas KD of NBCn1 or MCT4 increased tumor-free survival and decreased
      in vitro proliferation rate and colony growth in soft agar, KD of NHE1 did not
      have these effects. Moreover, only MCT4 KD reduced Akt kinase activity, PARP and
      CD147 expression and cell motility. This work reveals that different types of net
      acid extruding transporters, NHE1, NBCn1 and MCT4, are frequently expressed in
      patient mammary tumor tissue and demonstrates for the first time that they
      promote growth of TNBC human mammary tumors in vivo via distinct but overlapping
      mechanisms.

PMID- 29363135
TI  - What works in promoting and maintaining diversity in nursing programs.
AB  - BACKGROUND: The presence of a registered nurse (RN) workforce that is culturally
      and linguistically familiar with underrepresented minorities promotes effective
      health care for patients. A lack of diversity in the nursing education pipeline
      has led to a lack of diversity among registered nurses. METHODS: This qualitative
      descriptive study explored faculty perceptions of factors that attracted and
      maintained a diverse nursing student body at three different universities with
      large percentages of minority students. Websites were evaluated for diversity and
      audio-taped telephone interviews were conducted with nursing faculty using a
      semistructured set of open-ended questions. RESULTS: College location, online
      courses, community outreach programs, the presence of a diverse faculty and
      students, faculty accessibility, and financial aid with low college costs were
      identified as common factors in attracting and retaining minority students.
      Barriers included the cost for low socioeconomic status students, inadequate
      primary and secondary educational preparation, inherent bias in the institution,
      competition from other schools, admission policies, and limited diversity in
      leadership and faculty. CONCLUSIONS: Commitment to improving and maintaining
      diversity in nursing programs requires a sustained faculty effort to make the
      programs fit for the minority student.

PMID- 29363136
TI  - Effectiveness of supplementary irrigant agitation with the Finisher GF Brush on
      the debridement of oval root canals instrumented with the Gentlefile or nickel
      titanium rotary instruments.
AB  - AIM: To examine the efficacy of a novel supplementary irrigant agitating brush
      (Finisher GF Brush, MedicNRG, Kibbutz Afikim, Israel) on the debridement of root
      canals prepared with a novel stainless steel rotary instrumentation system
      (Gentlefile; MedicNRG), or nickel titanium rotary instruments in oval root
      canals. METHODOLOGY: Mandibular premolars (n = 72) were selected and divided
      randomly into three experimental groups (n = 24) after microCT scanning: group 1,
      canal preparation to rotary NiTi size 20, .04 taper (R20); group 2, rotary NiTi
      to size 25, .04 taper (R25) and group 3, Gentlefile size 23, .04 taper (GF).
      Specimens were subdivided into two subgroups: subgroup A, syringe-and-needle
      irrigation (SNI); subgroup B, Finisher GF Brush (GB). Ten untreated canals served
      as controls. Specimens were processed for histological evaluation, and the
      remaining pulp tissue (RPT) was measured. Data were analysed using Mann-Whitney
      and Kruskal-Wallis tests (P = 0.05). RESULTS: All experimental groups had
      significantly less RPT than the control (P < 0.05). Group 3B (GF-GB) had
      significantly less RPT than groups 1B (R20-GB) and 2B (R25-GF; P < 0.05). When
      irrigated with SNI, there was no significant difference in the RPT between the
      three groups (P > 0.05). When instrumented with R20, there was no significant
      difference between SNI and GF (P < 0.05) whilst GB had significantly less RPT
      than SNI for R25 (P < 0.05). CONCLUSIONS: Supplementary irrigant agitation with
      the Finisher GF Brush improved the debridement of canals prepared with Gentlefile
      and size 25, .04 taper rotary NiTi. Root canal debridement did not significantly
      differ between the instruments when syringe irrigation was used.

PMID- 29363137
TI  - A potential role for the silent information regulator 2 homologue 1 (SIRT1) in
      periapical periodontitis.
AB  - AIM: To investigate the role played by silent information regulator 2 homologue 1
      (SIRT1) during angiogenesis of periapical periodontitis. METHODOLOGY: Periapical
      granulomas were subjected to dual-colour immunofluorescence imaging and real-time
      polymerase chain reactions assaying the expression levels of SIRT1, vascular
      endothelial growth factor (VEGF) and VE-cadherin. The association between Ki-67
      and SIRT1 expression was also examined. Human umbilical vein endothelial cells
      (HUVECs) were treated with a combination of lipopolysaccharide and resveratrol (a
      SIRT1 activator) or sirtinol (a SIRT1 inhibitor); and the levels of mRNAs
      encoding SIRT1, VEGF and VE-cadherin were determined. HUVEC tube formation was
      assayed in the presence of resveratrol or sirtinol. The Mann-Whitney U-test or
      the Tukey-Kramer test was used for statistical analysis. RESULTS: Ki-67
      expressing cells, including endothelial cells, lay adjacent to SIRT1-expressing
      cells in periapical granulomas. In addition, SIRT1-expressing cells were detected
      adjacent to VEGF-expressing cells and VEGF- or VE-cadherin-expressing endothelial
      cells. SIRT1, VEGF and VE-cadherin mRNA expression levels in periapical
      granulomas were significantly higher (P = 0.0054, 0.0090 and 0.0090,
      respectively) than those in healthy gingival tissues. HUVECs treated with
      resveratrol exhibited significantly higher expression of mRNAs encoding SIRT1,
      VEGF and VE-cadherin (P = 0.0019, 0.00005 and 0.0045, respectively) compared with
      controls, but sirtinol inhibited such expression. Resveratrol caused HUVECs to
      form tube-like structures, whilst sirtinol inhibited this process. CONCLUSIONS:
      These findings suggest that SIRT1 may stimulate angiogenesis in periapical
      granulomas by triggering the proliferation of endothelial cells and inducing VEGF
      and VE-cadherin expression.

PMID- 29363138
TI  - Investigation of the HotDog patient warming system: detection of thermal
      gradients.
AB  - OBJECTIVE: To assess the performance of an active patient-warming device.
      MATERIALS AND METHODS: Temperatures of an active patient-warming device (HotDog
      system) were measured at various time points using an infrared thermometer. The
      study was conducted in two phases: Phase 1 compared temperatures among four
      different areas of the warming blanket. Phase 2 compared conditions simulating
      different scenarios using a weighted patient simulator. RESULTS: Phase 1: Three
      out of four positions on the warming blanket had significantly different
      temperature measurements. Phase 2: Temperature output by the warming blanket was
      reduced: (1) in the absence of the patient simulator placed across the blanket (
      1.9 degrees C, P=0.013); (2) if the patient simulator was placed away from the
      blanket sensor (-2.0 degrees C, P=0.009); and (3) if there was fluid between the
      patient simulator and warming blanket (-2.2 degrees C, P=0.004). In a majority of
      measurements (95%), the set temperature of 43 degrees C on the control unit was
      not reached (range, 29.8 to 42.9 degrees C) and 2.3% of measurements were higher
      (range, 43.1 to 45.8 degrees C) than the control unit set temperature of 43
      degrees C. CLINICAL SIGNIFICANCE: Measured temperatures on the active warming
      blanket did not reflect control unit settings. This could result in the potential
      for hyperthermic injury, ineffectual heating and uneven heat distribution.

PMID- 29363139
TI  - Genetic analysis of the liverwort Marchantia polymorpha reveals that R2R3MYB
      activation of flavonoid production in response to abiotic stress is an ancient
      character in land plants.
AB  - The flavonoid pathway is hypothesized to have evolved during land colonization by
      plants c. 450 Myr ago for protection against abiotic stresses. In angiosperms,
      R2R3MYB transcription factors are key for environmental regulation of flavonoid
      production. However, angiosperm R2R3MYB gene families are larger than those of
      basal plants, and it is not known whether the regulatory system is conserved
      across land plants. We examined whether R2R3MYBs regulate the flavonoid pathway
      in liverworts, one of the earliest diverging land plant lineages. We
      characterized MpMyb14 from the liverwort Marchantia polymorpha using genetic
      mutagenesis, transgenic overexpression, gene promoter analysis, and
      transcriptomic and chemical analysis. MpMyb14 is phylogenetically basal to
      characterized angiosperm R2R3MYB flavonoid regulators. Mpmyb14 knockout lines
      lost all red pigmentation from the flavonoid riccionidin A, whereas
      overexpression conferred production of large amounts of flavones and riccionidin
      A, activation of associated biosynthetic genes, and constitutive red
      pigmentation. MpMyb14 expression and flavonoid pigmentation were induced by light
      and nutrient-deprivation stress in M. polymorpha as for anthocyanins in
      angiosperms. MpMyb14 regulates stress-induced flavonoid production in M.
      polymorpha, and is essential for red pigmentation. This suggests that R2R3MYB
      regulated flavonoid production is a conserved character across land plants which
      arose early during land colonization.

PMID- 29363140
TI  - Pre-retirement job and the work-to-retirement occupational transition process in
      Australia: A review.
AB  - BACKGROUND: The transition from work to retirement is a complex process and
      unique experience with a relationship existing between work and retirement with
      implications for health in later life. This review explored the relationship
      between pre-retirement job and participation in the work-to-retirement transition
      process in Australia by exploring: (i) factors influencing retirement in relation
      to pre-retirement job; (ii) how jobs are classified; (iii) the effect of pre
      retirement job (based on categories) on this occupational transition; and (iv)
      the potential role for occupational therapy in this occupational transition.
      METHOD: An integrative literature review was completed. PRISMA guidelines were
      used. Study designs were analysed for methodological quality using the National
      Health and Medical Research Council levels of evidence. Thematic analysis
      determined retirement factors which were used to compare differences between
      jobs. RESULTS: This review included 15 papers. There were two Level III-2, one
      Level III-3 and 13 Level IV studies. Factors influencing retirement related to
      the stages of work, preparation, transition and retired. White collar and blue
      collar was the most common job classification system. Although white collar and
      blue collar worker definitions utilised were inconsistent, differences between
      the two groups were still determined in all stages. CONCLUSION: Differences in
      the work-to-retirement transition process, based on pre-retirement job, are
      evident. Understanding differences by job groupings may assist occupational
      therapists to understand individualised needs during this occupational transition
      and subsequent tailoring of interventions (both individual and group based) to
      enable engagement in meaningful occupation in the work-to-retirement occupational
      transition to effect active healthy ageing.

PMID- 29363141
TI  - Evaluation of tissue changes following intramuscular infiltration of lidocaine in
      rainbow trout Oncorhynchus mykiss.
AB  - Rainbow trout Oncorhynchus mykiss were infiltrated with either saline or
      lidocaine adjacent to the dorsal fin to assess histopathological changes.
      Infiltration was done as if it were being used as a local anaesthetic. Tissue
      lesions and associated tissue healing were examined over a period of 30 days.
      Most changes occurred at the cranial site of where the solution was first
      infiltrated. The infiltration of a dose of 10 mg kg-1 of lidocaine appears to
      have damaged the skeletal muscle and connective tissues more than a similar
      volume of saline, especially during the first 15 days. The primary changes
      included haemorrhage, inflammation and muscle degeneration and necrosis. By day
      30 post-infiltration inflammatory lesions were either nearly or completely
      absent, signs of myofibre regeneration were noted in only one fish. This
      experiment shows local anaesthetics and saline can produce localized tissue
      damage, especially during the first 2 weeks post infiltration. Care should be
      taken to allow the fish to heal for at least 30 days and probably more, no matter
      the solution administered, especially if giving repeated injections or
      infiltrations at the same site.

PMID- 29363142
TI  - Efficacy of the ProTaper retreatment system in removing Thermafil, GuttaCore or
      vertically compacted gutta-percha from curved root canals assessed by micro-CT.
AB  - AIM: To evaluate ex vivo the efficacy of ProTaper Universal Retreatment files
      (Dentsply Sirona, Ballaigues, Switzerland) in removing Thermafil, GuttaCore (both
      Dentsply Sirona) or vertically compacted gutta-percha from curved root canals
      using micro-CT. METHODOLOGY: Sixty curved molar roots with the same mean canal
      curvatures and radii in two directions were prepared using ProFile instruments
      (Dentsply Sirona) to size 30 with .04 taper and obturated with either Thermafil,
      GuttaCore or vertically compacted gutta-percha and AH Plus (n = 20). Specimens
      were retreated using the ProTaper Universal Retreatment files D1, D2 and D3 to
      working length, and root canal preparation was completed with ProTaper Next
      (Dentsply Sirona) to size *4. Percentages of residual filling material and
      dentine removal were assessed using micro-CT imaging. Working time and procedural
      errors were recorded. Statistical analysis was performed using Kruskal-Wallis and
      Wilcoxon tests. RESULTS: No significant differences between carrier-based and
      warm vertical compaction regarding residual filling material (14.2-19.3%) and
      dentine removal (2.7-3.2 mm3 ) were detected (P > 0.05). Time to reach working
      length was significantly faster for canals filled with GuttaCore than that
      observed for Thermafil and warm vertical compaction (P < 0.05). Five lateral
      perforations with the D3 file occurred during retreatment, one in the Thermafil
      and four in the vertical compaction group. CONCLUSIONS: Remaining filling
      material and dentine removal were similar for all canal filling techniques.
      Regaining working length was significantly faster for GuttaCore compared with
      Thermafil and vertically compacted gutta-percha. Procedural errors occurred
      during retreatment of severely curved root canals with the ProTaper Universal
      Retreatment files in 5 of 60 canals (8%).

PMID- 29363143
TI  - Putting the "Informed" in the informed consent process for implantable
      cardioverter-defibrillators: Addressing the needs of the elderly patient.
AB  - Implantable cardioverter defibrillator (ICD) management complexities challenge
      the ethos of fully informed consent, particularly for the typically multimorbid
      elderly patient considering the device for primary prevention. The Heart Rhythm
      Society recommends providers include discussion on the potential need for later
      device deactivation or nonreplacement at the time of first implant, and to
      revisit this at appropriate intervals. The initial consent procedure could meet
      this standard by incorporating the future need to discuss further such issues
      when the recipient's clinical condition changes to such an extent that
      defibrillation would no longer be beneficial. At the time of obtaining consent,
      some patients may lack the will or capacity to make medically complex decisions
      when it would be necessary for healthcare surrogate decision-makers to contribute
      to this process. Ensuring an appropriate level of understanding and response may
      be enhanced by the use of information and decision aids. With improved
      communication regarding the nuances of ICD therapy, device eligible patients, and
      those close to them, will be empowered with a better understanding of the nature,
      benefits, and risks of ICD implantation, allowing them to make treatment
      decisions consistent with their values.

PMID- 29363145
TI  - Can simple tank changes benefit the welfare of laboratory zebrafish Danio rerio?
AB  - This study examined the effects of simple changes in the tank environment on the
      wellbeing of laboratory-maintained zebrafish Danio rerio. Groups of D. rerio were
      either housed in stable environments (where they were maintained in the same
      tanks throughout the study) or in environments subject to change (where they were
      periodically moved to novel but identical tanks) and the effects of these
      treatments on morphometry, reproductive success and aggressive behaviour
      assessed. No effect of simple tank changes was found on body condition,
      reproductive output or aggression, for the periods of time studied, indicating
      that more complex scenarios in housing tank conditions are required for
      significant welfare benefits for captive D. rerio.

PMID- 29363144
TI  - Pulmonary arterial hypertension reduces energy efficiency of right, but not left,
      rat ventricular trabeculae.
AB  - KEY POINTS: Pulmonary arterial hypertension (PAH) triggers right ventricle (RV)
      hypertrophy and left ventricle (LV) atrophy, which progressively leads to heart
      failure. We designed experiments under conditions mimicking those encountered by
      the heart in vivo that allowed us to investigate whether consequent structural
      and functional remodelling of the ventricles affects their respective energy
      efficiencies. We found that peak work output was lower in RV trabeculae from PAH
      rats due to reduced extent and velocity of shortening. However, their suprabasal
      enthalpy was unaffected due to increased activation heat, resulting in reduced
      suprabasal efficiency. There was no effect of PAH on LV suprabasal efficiency. We
      conclude that the mechanism underlying the reduced energy efficiency of
      hypertrophied RV tissues is attributable to the increased energy cost of Ca2+
      cycling, whereas atrophied LV tissues still maintain normal mechano-energetic
      performance. ABSTRACT: Pulmonary arterial hypertension (PAH) greatly increases
      the afterload on the right ventricle (RV), triggering RV hypertrophy, which
      progressively leads to RV failure. In contrast, the disease reduces the passive
      filling pressure of the left ventricle (LV), resulting in LV atrophy. We
      investigated whether these distinct structural and functional consequences to the
      ventricles affect their respective energy efficiencies. We studied trabeculae
      isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and
      their respective Control groups. Trabeculae were mounted in a calorimeter at 37
      degrees C. While contracting at 5 Hz, they were subjected to stress-length work
      loops over a wide range of afterloads. They were subsequently required to undergo
      a series of isometric contractions at various muscle lengths. In both protocols,
      stress production, length change and suprabasal heat output were simultaneously
      measured. We found that RV trabeculae from PAH rats generated higher activation
      heat, but developed normal active stress. Their peak external work output was
      lower due to reduced extent and velocity of shortening. Despite lower peak work
      output, suprabasal enthalpy was unaffected, thereby rendering suprabasal
      efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast,
      LV trabeculae from PAH rats maintained normal mechano-energetic performance.
      Pulmonary arterial hypertension reduces the suprabasal energy efficiency of
      hypertrophied right ventricular tissues as a consequence of the increased energy
      cost of Ca2+ cycling.

PMID- 29363146
TI  - Interesting activity of pegylated liposomal doxorubicin in primary refractory and
      multirelapsed Hodgkin lymphoma patients: bridge to transplant.

PMID- 29363147
TI  - Differences in root canal system configuration in human permanent teeth within
      different age groups.
AB  - AIM: To analyse the differences in root canal system configuration in patients
      belonging to different age groups using cone beam computed tomography (CBCT)
      technology. METHODOLOGY: CBCT examinations from a pre-existing database were
      accessed. Patients were divided according to age groups: '<=20 years', '21-40
      years', '41-60 years' and '>=61 years'. Each group included tooth data regarding
      their root canal system configurations according to the Vertucci classification
      and its supplementary configurations. Cohen kappa coefficient of agreement was
      calculated to evaluate observer reliability. RESULTS: Overall 12 325 teeth from
      670 patients were included. Most of the root groups had higher or equal
      prevalence of Vertucci type I configurations in the younger groups whilst
      presenting a greater tendency for multiple root canal system configurations in
      older patients, mainly Vertucci type II in both maxillary and mandibular second
      premolars and in the distal root of the mandibular first molar. The Cohen kappa
      coefficient of agreement was 89.4 +/- 1.8%. CONCLUSION: Clinicians should be
      aware that the root canal system configuration changes over a lifetime. In this
      study, the most affected teeth were the second premolars and the distal root of
      mandibular first molars.

PMID- 29363148
TI  - Association between bacteria occurring in the apical canal system and expression
      of bone-resorbing mediators and matrix metalloproteinases in apical
      periodontitis.
AB  - AIM: To evaluate the association between the presence of selected bacterial
      species/groups in the apical root canal and expression of mediators of soft and
      bone tissue destruction in apical periodontitis lesions. Relationships between
      bacteria and some other features of apical periodontitis were also investigated.
      METHODOLOGY: Seventeen freshly extracted teeth with pulp necrosis and apical
      periodontitis were included. The apical root segment was sectioned and
      cryopulverized; DNA was extracted and evaluated for the presence of 9 bacterial
      species/groups using real-time polymerase chain reaction. Lesions were processed
      for histopathological and immunohistochemical analyses, which targeted matrix
      metalloproteinase-2 (MMP-2) and -9 (MMP-9), receptor activator of NFkappaB
      (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). Associations of the target
      bacteria with expression of these mediators, presence of symptoms, lesion size
      and histopathological diagnosis were evaluated. Data were analysed using the chi
      square, Fisher's exact, Mann-Whitney and Pearson tests. P values lower than 0.05
      were considered significant. RESULTS: All pulverized apical root samples were
      positive for bacteria. The most prevalent taxa were Actinobacteria (53%),
      Streptococcus species (35%), Fusobacterium species and Parvimonas micra (18%).
      The target mediators exhibited a high mean expression in the lesions (MMP-2: 82%;
      MMP-9: 73%; RANK: 78%; RANKL; 81%; OPG; 83%). Mean RANKL:OPG ratio was
      significantly higher in granulomas than cysts (P < 0.05, Mann-Whitney test).
      Actinobacteria were associated with granulomas, higher MMP-2 expression, lower
      OPG expression, and higher RANKL:OPG ratio (P < 0.05 for all, Fisher's exact test
      or Mann-Whitney test). No other significant associations were found. CONCLUSION:
      Actinobacteria may play an important role in the active phase of soft and bone
      tissue destruction in apical periodontitis.

PMID- 29363149
TI  - Prolonged survival after second autologous transplantation and lenalidomide
      maintenance for salvage treatment of myeloma patients at first relapse after
      prior autograft.
AB  - Autologous stem cell transplantation (ASCT) as part of the primary therapy in
      multiple myeloma (MM) is standard practice. In contrast, the role of a second
      ASCT (ASCT2) and subsequent lenalidomide maintenance for relapsed disease remains
      unclear. In this study, we analysed 86 consecutive MM patients with a first
      relapse after prior ASCT receiving either a second ASCT or conventional
      chemotherapy. After a median follow-up of 37.7 months since first relapse, 54
      (62.8%) patients were still alive and 29 (33.7%) without progression. Sixty-one
      (71.0%) patients received ASCT2 and had better progression-free survival (PFS)
      (30.2 versus 13.0 mo; P = .0262) and overall survival (OS) rates (129.6 versus
      33.5 mo; P = .0003) compared with 25 (29.0%) patients with conventional
      treatment. Patients relapsing later than 12 months after ASCT1 benefitted from a
      second ASCT with better PFS2 (P = .0179) and OS2 (P = .0009). Finally,
      lenalidomide maintenance after ASCT2 was associated with longer PFS (41.0 vs 21.6
      mo; P = .0034) and better OS (not yet reached vs 129.6 mo; P = .0434) compared
      with patients without maintenance. Our data suggest that a second ASCT and
      lenalidomide maintenance given at first relapse in MM after prior ASCT are
      associated with better survival rates.

PMID- 29363150
TI  - The Risk of Preterm Births Among Pregnant Women With Adenomyosis.
AB  - OBJECTIVES: Few studies have examined the effect of adenomyosis on pregnancy
      outcomes. We aimed to evaluate the risk of preterm birth and low birth weight in
      women with adenomyosis diagnosed during pregnancy. METHODS: A computerized
      ultrasonography database was used to identify singleton pregnant women with
      adenomyosis in the first trimester from January 2010 to December 2011. Only cases
      with a known pregnancy outcome were included. We reviewed the medical records and
      analyzed pregnancy outcomes according to the presence of adenomyosis and
      conception method. RESULTS: Among 11,173 singleton pregnant women, adenomyosis
      was detected in 88 (0.8%), and 8316 pregnant women (including 72 with
      adenomyosis) were included. The adenomyosis group was associated with
      significantly higher rates of preterm birth and low birth weight than the non
      adenomyosis group (12.5% versus 4.1%; P < .001; 13.9% versus 3.1%; P < .001,
      respectively). In a subgroup analysis according to the conception method,
      incidences of preterm birth and low birth weight were not different in the non
      adenomyosis group. However, the risks of preterm birth and low birth weight in
      the adenomyosis group were significantly higher in pregnant women who conceived
      by assisted reproductive technologies than in women who conceived naturally
      (28.0% versus 4.3%; P < .01; 28.0% versus 6.4%; P < .05, respectively).
      CONCLUSIONS: Ultrasonographic findings suggesting adenomyosis in early pregnancy
      were associated with increased risks of preterm delivery and low birth weight in
      women who conceived with the use of assisted reproductive technologies but not in
      women who conceived spontaneously.

PMID- 29363151
TI  - Low-Intensity Pulsed Ultrasound Accelerates Traumatic Vertebral Fracture Healing
      by Coupling Proliferation of Type H Microvessels.
AB  - OBJECTIVES: Patients with traumatic vertebral fractures often have major
      associated postoperative morbidities such as healing failure and kyphosis. Low
      intensity pulsed ultrasound (US) has been found to promote bone fracture healing.
      The objectives of our study were to determine whether low-intensity pulsed US
      could promote traumatic vertebral fracture healing and to explore its inner
      mechanisms. METHODS: A rat model of traumatic vertebral fracture was created and
      treated with low-intensity pulsed US after surgery. At 4 weeks after surgery,
      radiographic, micro-computed tomography, and 3-dimensional reconstruction were
      used to assess the radiologic healing status; a histologic analysis was performed
      to evaluate the pathologic process and relationship between osteogenesis and type
      H microvessels. RESULTS: Well-remodeled trabecular meshworks were found in the
      low-intensity pulsed US treatment group compared to the control group. Micro
      computed tomography and 3-dimensional reconstruction revealed more and thicker
      trabeculae after low-intensity pulsed US treatment. Abundant chondrocytes, a
      newly formed bone marrow cavity, trabeculae, and microvessels were formed at the
      fracture sites. More osterix-positive osteoblasts were circling the newly formed
      bone meshwork and were situated at the interface of chondrocytes in the low
      intensity pulsed US treatment group. Type H microvessels were spreading around
      the newly formed trabecula, bone marrow cavity, osteoblasts, and interface of
      chondrocytes, with a larger mean vascular density in the low-intensity pulsed US
      group. CONCLUSIONS: Low-intensity pulsed US could accelerate traumatic vertebral
      fracture healing by temporally and spatially increasing chondrogenesis and
      osteoblast-induced osteogenesis coupled with angiogenesis of type H microvessels
      in a rat model of traumatic vertebral fracture.

PMID- 29363152
TI  - Plasma levels of innate immune mediators are associated with liver fibrosis in
      low parasite burden Schistosoma mansoni-infected individuals.
AB  - In the murine model, it was demonstrated that pro-inflammatory cytokines and
      chemokines are essential to the formation and modulation of Schistosoma-induced
      granulomatous inflammation. However, the relationship of these immune mediators
      and disease severity is hard to be established in naturally infected individuals.
      The current study evaluates the association between plasma concentrations of MIF,
      sTNF-R1, CCL3, CCL7 and CCL24 and schistosomiasis morbidity in Schistosoma
      mansoni-infected patients with a low parasite burden. For this propose, 97 S.
      mansoni-infected individuals were subjected to abdominal ultrasound analysis and
      clinical examination. Among them, 88 had plasma concentration of immune mediators
      estimated by ELISA assay. Multivariate linear regression models were used to
      evaluate the relationship between the plasma concentration of immune mediators
      and the variables investigated. Although most individuals presented low parasite
      burden, over 30% of them showed signs of fibrosis defined by ultrasound
      measurements and 2 patients had a severe form of schistosomiasis. No association
      between parasite burden and the plasma levels of chemokine/cytokines or disease
      severity was observed. There was a positive association between plasma
      concentration of CCL4, sTNF-R1, CCL3 and MIF with gall bladder thickness and/or
      with portal vein thickness that are liver fibrosis markers. In contrast, no
      association was found between CCL7 plasma concentrations with any of the
      schistosomiasis morbidity parameters evaluated. The data showed that CCL24,
      sTNFR1, MIF and CCL3 can be detected in plasma of S. mansoni-infected individuals
      and their concentration would be used as prognostic makers of Schistosoma-induced
      liver fibrosis, even in individuals with low parasite burden.

PMID- 29363153
TI  - Protective role of melatonin in cardiac ischemia-reperfusion injury: From
      pathogenesis to targeted therapy.
AB  - Acute myocardial infarction (MI) is a major cause of mortality and disability
      worldwide. In patients with MI, the treatment option for reducing acute
      myocardial ischemic injury and limiting MI size is timely and effective
      myocardial reperfusion using either thombolytic therapy or primary percutaneous
      coronary intervention (PCI). However, the procedure of reperfusion itself induces
      cardiomyocyte death, known as myocardial reperfusion injury, for which there is
      still no effective therapy. Recent evidence has depicted a promising role of
      melatonin, which possesses powerful antioxidative and anti-inflammatory
      properties, in the prevention of ischemia-reperfusion (IR) injury and the
      protection against cardiomyocyte death. A number of reports explored the
      mechanism of action behind melatonin-induced beneficial effects against
      myocardial IR injury. In this review, we summarize the research progress related
      to IR injury and discuss the unique actions of melatonin as a protective agent.
      Furthermore, the possible mechanisms responsible for the myocardial benefits of
      melatonin against reperfusion injury are listed with the prospect of the use of
      melatonin in clinical application.

PMID- 29363154
TI  - Nonalcoholic Fatty Liver Is Associated With Further Left Ventricular
      Abnormalities in Patients With Type 2 Diabetes Mellitus: A 3-Dimensional Speckle
      Tracking Study.
AB  - OBJECTIVES: The aim of this study was to detect left ventricular (LV) structure
      and function abnormalities in patients with type 2 diabetes mellitus with or
      without nonalcoholic fatty liver (NAFL) using 3-dimensional speckle-tracking
      echocardiography. METHODS: Eighty patients with type 2 diabetes and a normal LV
      ejection fraction (>=55%), including 40 with coexistent NAFL, and 40 age- and sex
      matched control participants were recruited. Conventional echocardiography and 3
      dimensional speckle-tracking echocardiography were performed, and global
      longitudinal strain, global circumferential strain, global area strain, and
      global radial strain values were measured. RESULTS: Significant differences in 2
      dimensional LV functional patterns were found among the 3 groups (P = .031), and
      LV hypertrophy was the most prevalent in patients with diabetes and NAFL. The
      patients with diabetes only had significantly lower global longitudinal strain,
      global circumferential strain, and global radial strain than the controls (all P
      < .05). The patients with diabetes and NAFL had severely lower global
      longitudinal strain, global circumferential strain, global area strain, and
      global radial strain than the controls (all P < .001), and they also had severely
      lower global longitudinal strain, global area strain, and global radial strain
      than the patients with diabetes only (all P < 0.001). The hemoglobin A1c level
      and NAFL were independently associated with strain values in all patients with
      diabetes. The strain values in multiple directions (>=2 of global longitudinal,
      global circumferential, global area, and global radial strain) decreased
      significantly in the patients with diabetes and moderate and severe NAFL compared
      to those with mild NAFL (all P < .05). CONCLUSIONS: Nonalcoholic fatty liver
      could aggravate LV hypertrophy and dysfunction in patients with type 2 diabetes.
      The combined application of conventional and 3-dimensional speckle-tracking
      echocardiography could detect these asymptomatic preclinical abnormalities.

PMID- 29363156
TI  - Transcriptional patterns associated with BDCA3 expression on BDCA1+ myeloid
      dendritic cells.
AB  - Myeloid dendritic cells, including BDCA3hi DCs and BDCA1+ DCs (hereafter dubbed
      DC1 and DC2 for clarity), play a pivotal role in the induction and regulation of
      immune responses. Interestingly, a fraction of DC2 also express low to
      intermediate levels of BDCA3. It is unknown whether BDCA3+ DC2 also share other
      traits with DC1 that are absent in BDCA3- DC2 and/or whether BDCA3 expression
      renders DC2 functionally distinct from their BDCA3-lacking counterparts. Here, we
      used expression analysis on a predefined set of immunology-related genes to
      determine divergence between BDCA3-positive and BDCA3-negative DC2 and their
      relation to bona fide BDCA3hi DC1. Results showed that mRNA fingerprints of
      BDCA3+ DC2 and BDCA3- DC2 are very similar, and clearly distinct from that of
      DC1. Differences in mRNA expression, however, were observed between BDCA3+ DC2
      and BDCA3- DC2 that pointed toward a more activated status of BDCA3+ DC2. In line
      with this, higher steady state maturation marker expression and TLR-induced
      maturation marker expression and inflammatory cytokine production by BDCA3+ DC2
      were observed. This dataset provides insight into the relationship between
      myeloid DC populations and contributes to further understanding of DC
      immunobiology.

PMID- 29363157
TI  - Population-based study of mantle cell lymphoma: Improvements in survival only
      seen in younger patients.

PMID- 29363158
TI  - A possible direct action of oxytocin on spermatogenesis and steroidogenesis in
      pre-pubertal mouse.
AB  - The aim of this study was to evaluate the effects of in vivo and in vitro
      treatments of oxytocin (OT) on the testis of pre-pubertal mice. The OT treatment
      produced significant changes in the spermatogenic and steroidogenic activity by
      increasing expression of OT-receptor in the testis of pre-pubertal mice.
      Treatment with OT showed increased proliferation of germ cells as indicated by
      increased number of spermatocytes and round spermatids. Dose-dependent increase
      in expression of PCNA, Bcl-2 and AR proteins was observed in the testis of OT
      treated mice as compared with the control and further supports the role of OT in
      germ cell proliferation and survival. The pre-pubertal mice treated with
      increasing dose of OT showed significant increase in testosterone synthesis due
      to dose-dependent stimulatory effects on 3beta-HSD activity and increased
      expression of STAR, LH-receptor (LH-R) and gonadotrophin-releasing hormone
      receptor (GnRH-R) proteins in the testis. The in vitro study has confirmed in
      vivo finding showing direct action of OT on testicular steroidogenesis. Thus, OT
      stimulates testicular spermatogenesis and steroidogenesis by directly acting on
      testis in mice.

PMID- 29363159
TI  - Effects of a physical activity programme in the school setting on physical
      fitness in preschool children.
AB  - AIM: The purpose of this study was to examine the effects of a 10-week aerobic
      games programme on physical fitness. METHODS: One hundred eleven children, aged 3
      to 6 years, participated in this study; 60 children were male (age: 4.28 +/- 0.61
      years old), and 51 were female (age 4.59 +/- 0.49 years old). Participants were
      randomly assigned to an experimental group (EG; n = 56) and a control group (CG;
      n = 55). A fitness test battery previously validated for preschoolers was used.
      The children in the EG performed 3 weekly training sessions of physical activity
      in a classroom during a 10-week period. Every EG session lasted about 30 min.
      RESULTS: There were no significant differences in any variable in the pretest
      between groups. In the posttest, the EG achieved better results in horizontal
      jump and sprint. In relation to posttest-pretest differences, the EG showed a
      greater increase in horizontal jump, sprint, and endurance. CONCLUSION: An
      aerobic games programme in the school setting improved physical fitness in
      preschool children.

PMID- 29363155
TI  - Critical evaluation of causality assessment of herb-drug interactions in
      patients.
AB  - The aim of this review was to assess the severity of adverse drug reactions
      (ADRs) due to herb-drug interactions (HDI) in patients taking herbs and
      prescribed medications based on published evidence. Electronic databases of
      PubMed, the Cochrane Library, Medline and Scopus were searched for randomized or
      nonrandomized clinical studies, case-control and case reports of HDI. The data
      were extracted and the causal relationship of ADRs as consequences of HDI
      assessed using Horn's drug interaction probability scale or Roussel Uclaf
      Causality Assessment Method scoring systems. The mechanism of interaction was
      ascertained using Stockley's herbal medicine interaction companion. Forty-nine
      case reports and two observational studies with 15 cases of ADRs were recorded.
      The majority of the patients were diagnosed with cardiovascular diseases
      (30.60%), cancer (22.45%) and renal transplants (16.32%) receiving mostly
      warfarin, alkylating agents and cyclosporine, respectively. HDI occurred in
      patients resulting in clinical ADRs with different severity. Patients may poorly
      respond to therapeutic agents or develop toxicity due to severe HDI, which in
      either scenario may increase the cost of treatment and/or lead to or prolong
      patient hospitalization. It is warranted to increase patient awareness of the
      potential interaction between herbs and prescribed medicines and their
      consequences to curb HDI as a potential health problem.

PMID- 29363160
TI  - Targeted deletion of c-Met in thymic epithelial cells leads to an autoimmune
      phenotype.
AB  - Hepatocyte growth factor (HGF) and its receptor c-Met signaling have been
      implicated in regulating various types of cells including epithelial cells. We
      have previously reported that c-Met is expressed by thymic epithelial cells
      (TECs), and that in vivo administration of hybrid cytokines containing IL-7 and
      the beta- or alpha-chain of HGF significantly increase the number of TECs. In
      order to study the role of c-Met signaling in TECs, we generated conditional
      knockout (cKO) mice in which c-Met was specifically deleted in TECs using a Foxn1
      Cre transgene. We show here that c-Met deficiency in TECs results in age
      progressive reduction in TEC number and reduced number of regulatory T cells.
      Consequently, c-Met TEC cKO mice displayed an autoimmune phenotype. Thus, c-Met
      signaling in TECs is important for the maintenance of TECs and immune self
      tolerance.

PMID- 29363161
TI  - Subsets of activated monocytes and markers of inflammation in incipient and
      progressed multiple sclerosis.
AB  - Multiple sclerosis (MS) is an immune mediated, inflammatory and demyelinating
      disease of the central nervous system (CNS). Substantial evidence points toward
      monocytes and macrophages playing prominent roles early in disease, mediating
      both pro- and anti-inflammatory responses. Monocytes are subdivided into three
      subsets depending on the expression of CD14 and CD16, representing different
      stages of inflammatory activation. To investigate their involvement in MS,
      peripheral blood mononuclear cells from 40 patients with incipient or progressed
      MS and 20 healthy controls were characterized ex vivo. In MS samples, we
      demonstrate a highly significant increase in nonclassical monocytes
      (CD14+CD16++), with a concomitant significant reduction in classical monocytes
      (CD14++CD16-) compared with healthy controls. Also, a significant reduction in
      the surface expression of CD40, CD163, and CD192 was found, attributable to the
      upregulation of the nonclassical monocytes. In addition, significantly increased
      levels of human endogenous retrovirus (HERV) envelope (Env) epitopes, encoded by
      both HERV-H/F and HERV-W, were specifically found on nonclassical monocytes from
      patients with MS; emphasizing their involvement in MS disease. In parallel, serum
      and cerebrospinal fluid (CSF) samples were analyzed for soluble biomarkers of
      inflammation and neurodegeneration. For sCD163 versus CD163, no significant
      correlations were found, whereas highly significant correlations between levels
      of soluble neopterine and the intermediate monocyte (CD14++CD16+) population was
      found, as were correlations between levels of soluble osteopontin and the HERV
      Env expression on nonclassical monocytes. The results from this study emphasize
      the relevance of further focus on monocyte subsets, particularly the nonclassical
      monocytes in monitoring of inflammatory diseases.

PMID- 29363162
TI  - Inflammatory monocytes contribute to the persistence of CXCR3hi CX3CR1lo
      circulating and lung-resident memory CD8+ T cells following respiratory virus
      infection.
AB  - Phenotypically diverse memory CD8+ T cells are present in the lungs that either
      re-circulate or reside within the tissue. Understanding the key cellular
      interactions that regulate the generation and then persistence of these different
      subsets is of great interest. Recently, DNGR-1+ dendritic cell (DC) mediated
      priming was reported to control the generation of lung-resident but not
      circulating memory cells following respiratory viral infection. Here, we report
      an important role for Ly6C+ inflammatory monocytes (IMs) in contributing to the
      persistence of memory CD8+ T cells but not their generation. Effector CD8+ T
      cells expanded and contracted normally in the absence of IMs, but the memory
      compartment declined significantly over time. Quite unexpectedly, this defect was
      confined to tissue resident and circulating CXCR3hi CX3CR1lo memory cells but not
      CXCR3hi CX3CR1int and CXCR3lo CX3CR1hi subsets. Thus, two developmentally
      distinct innate cells orchestrate the generation and persistence of memory T cell
      subsets following a respiratory virus infection. See also: News and Commentary by
      Lafouresse & Groom.

PMID- 29363164
TI  - Superior properties of CellTrace YellowTM as a division tracking dye for human
      and murine lymphocytes.
AB  - The discovery of cell division tracking properties of 5-(and-6)
      carboxyfluorescein diacetate succinimidyl ester (CFSE) by Lyons and Parish in
      1994 led to a broad range of new methods and numerous important biological
      discoveries. After labeling, CFSE is attached to free amine groups and
      intracellular proteins in the cytoplasm and nucleus of a cell, and halves in
      fluorescence intensity with each round of cell division, enabling enumeration of
      the number of divisions a cell has undergone. A range of popular division
      tracking dyes were subsequently developed, including CellTrace Violet (CTV),
      making available the green fluorescent channel previously occupied by CFSE. More
      recently, CellTrace Yellow (CTY) and CellTrace Far Red (CTFR), each with unique
      fluorescence properties, were introduced. In a comparison, we found that the
      fluorescence values of both dyes were well separated from autofluorescence, and
      enabled a greater number of divisions to be identified than CTV, before this
      limit was reached. These new dyes provided clear and well-separated peaks for
      both murine and human B lymphocytes, and should find wide application. The range
      of excitation/emission spectra available for division tracking dyes now also
      facilitates multiplexing, that is, the labeling of cells with different
      combinations of dyes to give a unique fluorescence signature, allowing single
      cell in vitro and in vivo tracking. The combinatorial possibilities are
      significantly increased with these additional dyes.

PMID- 29363163
TI  - LncRNA-RP11-714G18.1 suppresses vascular cell migration via directly targeting
      LRP2BP.
AB  - Atherosclerotic cardiovascular disease is considered as the leading cause of
      mortality and morbidity worldwide. Accumulating evidence supports an important
      role for long noncoding RNA (lncRNA) in the pathogenesis of atherosclerosis.
      Nevertheless, the role of lncRNA in atherosclerosis-associated vascular
      dysfunction and the underlying mechanism remain elusive. Here, using microarray
      analysis, we identified a novel lncRNA RP11-714G18.1 with significant reduced
      expression in human advanced atherosclerotic plaque tissues. We demonstrated in
      both human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) that
      RP11-714G18.1 impaired cell migration, reduced the adhesion of ECs to monocytes,
      suppressed the neoangiogenesis, decreased apoptosis of VSMCs and promoted nitric
      oxide production. Mechanistically, RP11-714G18.1 could directly bind to its
      nearby gene LRP2BP and increased the expression of LRP2BP. Moreover, we showed
      that RP11-714G18.1 impaired cell migration through LRP2BP-mediated downregulation
      of matrix metalloproteinase (MMP)1 in both ECs and VSMCs. In atherosclerotic
      patients, the serum levels of LRP2BP were positively correlated with high-density
      lipoprotein cholesterol, but negatively correlated with cardiac troponin I. Our
      study suggests that RP11-714G18.1 may play an athero-protective role by
      inhibiting vascular cell migration via RP11-714G18.1/LRP2BP/MMP1 signaling
      pathway, and targeting the pathway may provide new therapeutic approaches for
      atherosclerosis.

PMID- 29363165
TI  - Lower Bone Density, Impaired Microarchitecture, and Strength Predict Future
      Fragility Fracture in Postmenopausal Women: 5-Year Follow-up of the Calgary CaMos
      Cohort.
AB  - The aim of this prospective study was to use high-resolution peripheral
      quantitative computed tomography (HR-pQCT) to determine if baseline skeletal
      parameters can predict incident fragility fracture in women and, secondly, to
      establish if women that fracture lose bone at a faster rate than those who do not
      fracture. Women older than 60 years who experienced a fragility fracture during
      the 5-year follow-up period (incident fracture group, n = 22) were compared with
      those who did not experience a fragility fracture during the study (n = 127).
      After image registration between baseline and follow-up measures, standard and
      cortical morphological analyses were conducted. Odds ratios were calculated for
      baseline values and annualized percent change of HR-pQCT and finite element
      variables. At the radius, baseline HR-pQCT results show women who fractured had
      lower total bone mineral density (Tt.BMD; 19%), trabecular bone mineral density
      (Tb.BMD; 25%), and trabecular number (Tb.N; 14%), with higher trabecular
      separation (Tb.Sp; 19%) than women who did not fracture. At the tibia, women with
      incident fracture had lower Tt.BMD (15%), Tb.BMD (12%), cortical thickness
      (Ct.Th; 14%), cortical area (Ct.Ar; 12%), and failure load (10%) with higher
      total area (Tt.Ar; 7%) and trabecular area (Tb.Ar; 10%) than women who did not
      fracture. Odds ratios (ORs) at the radius revealed every SD decrease of Tt.BMD
      (OR = 2.1), Tb.BMD (OR = 2.0), and Tb.N (OR = 1.7) was associated with a
      significantly increased likelihood of fragility fracture. At the tibia, every SD
      decrease in Tt.BMD (OR = 2.1), Tb.BMD (OR = 1.7), Ct.Th (OR = 2.2), Ct.Ar (OR =
      1.9), and failure load (OR = 1.7) were associated with a significantly increased
      likelihood of fragility fracture. Irrespective of scanning modality, the
      annualized percent rate of bone loss was not different between fracture groups.
      The results suggest baseline bone density, microarchitecture, and strength rather
      than change in these variables are associated with incident fragility fractures
      in women older than 60 years. Furthermore, irrespective of fragility fracture
      status, women experienced changes in skeletal health at a similar rate. (c) 2017
      American Society for Bone and Mineral Research.

PMID- 29363166
TI  - Use of social media is associated with short sleep duration in a dose-response
      manner in students aged 11 to 20 years.
AB  - AIM: This study examined the association between social media and sleep duration
      among Canadian students aged 11-20. METHODS: Data from 5242 students were
      obtained from the 2015 Ontario Student Drug Use and Health Survey, a province
      wide, school-based survey that has been conducted every two years since 1977. We
      measured the respondents' sleep duration against the recommended ranges of 9-11 h
      per night at 11-13 years of age, 8-10 h at 14-17 and 7-9 h per night for those
      aged 18 years or more. RESULTS: Overall, 36.4% of students met or exceeded the
      recommended sleep duration and 63.6% slept less than recommended, with 73.4% of
      students reporting that they used social media for at least one hour per day.
      After adjusting for various covariates, the use of social media was associated
      with greater odds of short sleep duration in a dose-response manner (p for linear
      trend <0.001). Odds ratios ranged from 1.82 for social media use of at least one
      hour per day to 2.98 for at least five hours per day. CONCLUSION: Greater use of
      social media was associated with shorter sleep duration in a dose-response
      fashion among Canadian students aged 11-20.

PMID- 29363167
TI  - Endocytosed soluble cowpox virus protein CPXV012 inhibits antigen cross
      presentation in human monocyte-derived dendritic cells.
AB  - Viruses may interfere with the MHC class I antigen presentation pathway in order
      to avoid CD8+ T cell-mediated immunity. A key target within this pathway is the
      peptide transporter TAP. This transporter plays a central role in MHC class I
      mediated peptide presentation of endogenous antigens. In addition, TAP plays a
      role in antigen cross-presentation of exogenously derived antigens by dendritic
      cells (DCs). In this study, a soluble form of the cowpox virus TAP inhibitor
      CPXV012 is synthesized for exogenous delivery into the antigen cross-presentation
      route of human monocyte-derived (mo)DCs. We show that soluble CPXV012 localizes
      to TAP+ compartments that carry internalized antigen and is a potent inhibitor of
      antigen cross-presentation. CPXV012 stimulates the prolonged deposition of
      antigen fragments in storage compartments of moDCs, as a result of reduced
      endosomal acidification and reduced antigen proteolysis when soluble CPXV012 is
      present. Thus, a dual function can be proposed for CPXV012: inhibition of TAP
      mediated peptide transport and inhibition of endosomal antigen degradation. We
      propose this second function for soluble CPXV012 can serve to interfere with
      antigen cross-presentation in a peptide transport-independent manner.

PMID- 29363169
TI  - Mutation analysis of the EBV-lymphoblastoid cell line cautions their use as
      antigen-presenting cells.
AB  - Lymphoblastoid cell lines (LCLs) have been widely used as professional antigen
      presenting cells (APCs). However, neoantigen-loaded LCLs could induce nonspecific
      T-cell response, which could be due to expression of both Epstein-Barr virus
      (EBV) antigens and nonsynonymous mutations arising in LCLs. Since the number of
      passages could influence mutational characteristics of LCLs, and moreover
      extensive proliferation of LCLs in vitro is necessary to activate T cells for
      immunotherapy, we comprehensively profiled mutational characteristics by
      comparing eight sets of B cells and matched high-passage LCLs using whole-exome
      sequencing in order to assess the effect of nonsynonymous mutations arising in
      LCLs on nonspecific T-cell response. We found 315 nongermline mutations
      (approximately 40mut/subject) randomly distributed across all chromosomes
      including 18 mutations in immunoglobulin V and J genes in eight LCLs, of which
      137 candidate neoantigens (approximately 17mut/subject) were identified. The
      underlying mutational processes linked to EBV-transformed LCLs could be
      attributed to activation induced cytidine deaminase gene expression which
      contributes to cytosine mutation clusters in LCLs through cytosine deamination.
      Pathways significantly enriched by nonsilent mutations of each LCL were totally
      different among all LCLs. In conclusion, high-passage LCLs may not be suitable to
      serve as APCs due to random nonsilent mutations, particularly for presentation of
      neoantigens of low immunogenicity, although further experimental proofs are
      needed.

PMID- 29363168
TI  - Yeast-insect associations: It takes guts.
AB  - Insects interact with microorganisms in several situations, ranging from the
      accidental interaction to locate attractive food or the acquisition of essential
      nutrients missing in the main food source. Despite a wealth of studies recently
      focused on bacteria, the interactions between insects and yeasts have relevant
      implications for both of the parties involved. The insect intestine shows several
      structural and physiological differences among species, but it is generally a
      hostile environment for many microorganisms, selecting against the most sensitive
      and at the same time guaranteeing a less competitive environment to resistant
      ones. An intensive characterization of the interactions between yeasts and
      insects has highlighted their relevance not only for attraction to food but also
      for the insect's development and behaviour. Conversely, some yeasts have been
      shown to benefit from interactions with insects, in some cases by being carried
      among different environments. In addition, the insect intestine may provide a
      place to reside for prolonged periods and possibly mate or generate sexual forms
      able to mate once back in the external environments. YEA-May-17-0084.R3.

PMID- 29363170
TI  - Intestinal overexpression of interleukin (IL)-15 promotes tissue eosinophilia and
      goblet cell hyperplasia.
AB  - Interleukin (IL)-15 overexpression in eosinophilic gastrointestinal disorders is
      reported, but IL-15's role in promoting eosinophilic gastroenteritis is largely
      unknown. Therefore, we generated enterocyte-overexpressed IL-15 transgenic mice
      using Fabpi promoter. The Fabpi-IL-15 (iIL-15) transgenic mice showed induced IL
      15 levels in the jejunum with a marked increase in jejunum eosinophils. However,
      no induction of eosinophilia in the blood or any other gastrointestinal segment
      was observed. Eosinophilia in the jejunum villus was substantially higher in iIL
      15 mice compared to wild-type mice. In addition, goblet cell hyperplasia was also
      observed in the jejunum of iIL-15 mice. Furthermore, a significant correlation
      between induced IL-15 transcript and the IL-18 transcripts was observed.
      Therefore, to further understand the role of IL-18 in IL-15 mice associated
      gastrointestinal disorders, we generated iIL-15/IL-18Ralpha-/- mice. Using these
      mice, we found that IL-18 has an important role in promoting IL-15-induced
      eosinophilia. As intestinal IL-15 overexpression is reported in food intolerance,
      we examined OVA intolerance in iIL-15 mice. The OVA-sensitized and challenged iIL
      15 mice experienced weight loss, diarrhea and eosinophilia in the jejunum. Taken
      together, our findings demonstrate that intestinal IL-15 overexpression induces
      IL-18-dependent eosinophilia and immunoglobulins in the intestine that promotes
      food allergic responses.

PMID- 29363171
TI  - Political populations of large carnivores.

PMID- 29363172
TI  - BCG vaccination drives accumulation and effector function of innate lymphoid
      cells in murine lungs.
AB  - The tuberculosis (TB) vaccine bacille Calmette-Guerin (BCG) prevents disseminated
      childhood TB; however, it fails to protect against the more prevalent pulmonary
      TB. Limited understanding of the immune response to Mycobacterium tuberculosis,
      the causative agent of TB, has hindered development of improved vaccines.
      Although memory CD4 T cells are considered the main mediators of protection
      against TB, recent studies suggest there are other key subsets that contribute to
      antimycobacterial immunity. To that end, innate cells may be involved in the
      protective response. In this study, we investigated the primary response of
      innate lymphoid cells (ILCs) to BCG exposure. Using a murine model, we showed
      that ILCs increased in number in the lungs and lymph nodes in response to BCG
      vaccination. Additionally, there was significant production of the
      antimycobacterial cytokine IFN-gamma by ILCs. As ILCs are located at mucosal
      sites, it was investigated whether mucosal vaccination (intranasal) stimulated an
      enhanced response compared to the traditional vaccination approach (intradermal
      or subcutaneous). Indeed, in response to intranasal vaccination, the number of
      ILCs, and IFN-gamma production in NK cells and ILC1s in the lungs and lymph
      nodes, were higher than that provoked through intradermal or subcutaneous
      vaccination. This work provides the first evidence that BCG vaccination activates
      ILCs, paving the way for future research to elucidate the protective potential of
      ILCs against mycobacterial infection. Additionally, the finding that lung ILCs
      respond rigorously to mucosal vaccination may have implications for the delivery
      of novel TB vaccines.

PMID- 29363173
TI  - MAIT cells: an historical and evolutionary perspective.
AB  - In humans, MAIT cells represent the most abundant T-cell subset reacting against
      bacteria. MAIT cells belong to the evolutionarily conserved family of "preset" T
      cells that includes also NKT cells. Both subsets are selected by double positive
      thymocytes leading to common features such as PLZF expression. Preset T cells
      correspond to subsets prepositioned in specific tissue locations with
      preprogrammed versatile effector functions such as antimicrobial functions and
      possibly also metabolic control and tissue repair activity. Herein, we recall how
      several groups studying human samples discovered MAIT cells as T cells expressing
      either a restricted T-cell receptors (TCR) repertoire or homogeneous and singular
      phenotypic and functional characteristics. We then highlight the main
      evolutionary features of this subset and its restricting element, MR1 (MHC
      related protein (1) with a striking coevolution of TRAV1 and MR1. We introduce
      another evolutionarily conserved invariant TCRalpha chain coevolving with another
      MHC class Ib molecule, called MHX, sharing phylogenetic features with MR1. We
      finally discuss the relationship between MAIT cells and other subsets reacting to
      microbial antigens or to compounds presented by MR1 in light of confounding
      experimental issues.

PMID- 29363174
TI  - Automated digital image analysis (TrichoScan) in male patients with androgenetic
      alopecia; comparison with manual marking of hairs on trichoscopic images.

PMID- 29363175
TI  - Seborrheic keratoses mimicking melanoma unveiled by in vivo reflectance confocal
      microscopy.
AB  - BACKGROUND: Seborrheic keratoses (SebK) with atypical dermoscopy presentation are
      increasingly reported. These lesions do not exhibit typical dermoscopy features
      of SebK and sometimes mimic melanoma, thus complicating the differential
      diagnosis. Reflectance confocal microscopy (RCM) is a non-invasive tool, which
      allows an in vivo imaging of the skin. The study objectives were to evaluate the
      agreement between RCM classification and histological diagnoses, and the
      reliability of well-known RCM criteria for SebK in the identification of SebK
      with atypical dermoscopy presentation. MATERIALS AND METHODS: We retrospectively
      analysed at RCM excised lesions presenting in dermoscopy >=1 score at revisited 7
      point checklist. The study population consisted of cases showing no melanocytic
      RCM findings. Lesions were investigated for distinct non-melanocytic RCM
      features, blinded from histopathology diagnoses. Histopathology matching was then
      performed before statistical analysis. RESULTS: The study consisted of 117 cases,
      classified at RCM as SebK (71 cases), dermatofibroma (18 cases), basal cell
      carcinoma (13 cases), squamous cell carcinoma (2 cases), and "non-specific" (13
      cases). Overall K strength of agreement at histopathology matching proved 0.76.
      Of the 71 cases classified at RCM with SebK, agreement was achieved in 97%.
      CONCLUSION: Reflectance confocal microscopy classification proved high agreement
      with histopathology for SebK with atypical dermoscopy presentations, allowing an
      early differential diagnosis. RCM features in this group of lesions were similar
      to those described for typical cases of SebK, and may assist clinician therapy
      decision making, whilst avoiding unnecessary excisions.

PMID- 29363176
TI  - Differences in Perceptions of and Practices Regarding Treatment of Alcohol Use
      Disorders Among VA Primary Care Providers in Urban and Rural Clinics.
AB  - BACKGROUND: Effective behavioral and pharmacological treatments are available and
      recommended for patients with alcohol use disorders (AUD) but rarely received.
      Barriers to receipt and provision of evidence-based AUD treatments delivered by
      specialists may be greatest in rural areas. METHODS: A targeted subanalysis of
      qualitative interview data collected from primary care providers at 5 Veterans
      Affairs clinics was conducted to identify differences in provider perceptions and
      practices regarding AUD treatment across urban and rural clinics. Key contacts
      were used to recruit 24 providers from 3 "urban" clinics at medical centers and 2
      "rural" community-based outpatient clinics. Providers completed 30-minute
      semistructured interviews, which were recorded, transcribed, and analyzed using
      inductive content analysis. RESULTS: Thirteen urban and 11 rural providers
      participated. Urban and rural providers differed regarding referral practices and
      in perceptions of availability and utility of specialty addictions treatment.
      Urban providers described referral to specialty treatment as standard practice,
      while rural providers reported substantial barriers to specialty care access and
      infrequent specialty care referral. Urban providers viewed specialty addictions
      treatment as accessible and comprehensive, and perceived addictions providers as
      "experts" and collaborators, whereas rural providers perceived inadequate support
      from the health care system for AUD treatment. Urban providers desired greater
      integration with specialty addictions care while rural providers wanted access to
      local addictions treatment resources. CONCLUSIONS: Providers in rural settings
      view referral to specialty addictions treatment as impractical and resources
      inadequate to treat AUD. Additional work is needed to understand the unique needs
      of rural clinics and decrease barriers to AUD treatment.

PMID- 29363177
TI  - Modeling children's development in gross motor coordination reveals key
      modifiable determinants. An allometric approach.
AB  - Children change their body size, shape, and gross motor coordination (GMC) as
      they grow. Further, GMC is expected to link to changes in children's body size,
      physical activity (PA), and physical fitness (PF). The objective was to model GMC
      changes in children followed longitudinally and to investigate associations
      between these changes and PA and PF levels. A total of 245 children (122 girls)
      were observed at 6 years of age and followed annually until 9 years. A sequence
      of allometric models was fitted, that is, 1. body mass, stature, and PA; 2.
      addition of four PF tests; 3. addition of four more PF tests. In Model 1, changes
      in GMC are nonlinear, and body mass (-0.60 +/- 0.07, P < .001) and stature (2.91
      +/- 0.35, P < .001) parameter estimates were significant suggesting children with
      a more linear body size/shape showed higher GMC performances. Girls tend to
      outperform boys across time, and PA was not associated with GMC changes. Model 2
      fitted the data better, and the PF tests (handgrip, standing long jump, 50-yard
      dash, and shuttle run) were significantly linked to GMC change. In Model 3,
      adding the remaining PF tests did not change the order of any factors importance.
      The greatest GMC changes were achieved by children whose body size/shape has an
      ectomorphic dominance across the years. Considering that leaner and physically
      fitter children tended to be more coordinated, physical education should also
      focus on PF development in components related to muscular strength, speed,
      agility, and aerobic capacity, along with nutritional education to reduce fat
      mass.

PMID- 29363178
TI  - High-frequency ultrasound-based differentiation between nodular dermal filler
      deposits and foreign body granulomas.
AB  - BACKGROUND: The number of procedures involving dermal filler injection is still
      on the rise. Although their safety is improving, not all complications can be
      avoided. The late complications manifesting as nodules or granulomas pose a
      particular diagnostic and therapeutic challenge, due to the lack of uniform
      standards or guidelines. High-frequency, ultrasound imaging appears to be a
      useful method for distinguishing between granulomas and nodular dermal filler
      deposits. AIM: The aim of the paper was to evaluate the utility of high frequency
      ultrasound imaging for distinguishing between foreign body granulomas and nodular
      dermal filler deposits. MATERIAL AND METHODS: Eleven females aged 21-66 years
      (mean age of 43.6 years old) who had soft tissue fillers injected were enrolled.
      All patients had a high-frequency ultrasound scan of the involved skin area
      performed. The shape, margins, area, location and echogenicity of the lesions
      were assessed. Additionally, the lesions were evaluated histologically and
      photographs were taken. RESULTS: The analysis indicated differences between the
      ultrasound image of granulomas and dermal filler deposits. Characteristic
      ultrasound features of granulomas include oval shape and blurred, irregular outer
      edges. Small hyperechoic areas were seen inside the granulomas. The deposits were
      anechogenic, with sharp, regular borders. CONCLUSIONS: High-frequency ultrasound
      imaging enables distinguishing between granulomas and nodules-dermal filler
      deposits, which form after dermal filler injections.

PMID- 29363179
TI  - HLA-DR+ NK cells are mostly characterized by less mature phenotype and high
      functional activity.
AB  - NK cells change their phenotype and functional characteristics during activation.
      In this work, we searched for a relationship of HLA-DR expression with
      differentiation stages and functional activity of NK cells ex vivo and stimulated
      in vitro with IL-2 challenged with gene modified feeder K562 cells expressing
      membrane-bound IL-21 (K562-mbIL21). This stimulation technique has been described
      for NK cell expansion in clinical use. We have observed that HLA-DR expression in
      freshly isolated circulating NK cells was mostly associated with less
      differentiated CD56bright CD57- cells, although in some individuals it could also
      be found in terminally differentiated CD57+ cells. Ex vivo HLA-DR+ NK cells
      possessed better capacity to produce IFN-gamma in response to cytokine
      stimulation compared to their HLA-DR- counterparts. In vitro activation with IL-2
      and K562-mbIL21 induces an increase in HLA-DR-positive NK cell proportion, again
      mostly among CD56bright CD57- NK cells. This happened in particular due to
      appearance of HLA-DR+ expression de novo in HLA-DR-negative cells. Acquired in
      vitro HLA-DR expression was associated with NK cell proliferation activity, more
      intense cytokine-induced IFN-gamma production, increased degranulation toward
      feeder cells, and higher expression of CD86 and NKG2D. Thus, stimulation with IL
      2/K562-mbIL21 causes a significant phenotype and functional shift during NK cell
      activation and expansion.

PMID- 29363180
TI  - Separate roles of IL-6 and oncostatin M in mouse macrophage polarization in vitro
      and in vivo.
AB  - Arginase-1 (Arg-1)-expressing M2-like macrophages are associated with Th2-skewed
      immune responses, allergic airway pathology, ectopic B16 melanoma cancer growth
      in murine models, and can be induced by Oncostatin M (OSM) transient
      overexpression in vivo. Here, we compare OSM to the gp130-cytokine IL-6 in
      mediating macrophage polarization, and find that IL-6 overexpression alone (Ad
      vector, AdIL-6) did not induce Arg-1 protein in mouse lungs at day 7, nor ectopic
      melanoma tumor growth at day 14, in contrast to overexpression of OSM (AdOSM).
      AdOSM elevated levels of IL-4, IL-5 and IL-13 in bronchoalveolar lavage fluid,
      whereas AdIL-6 did not. Bone marrow-derived macrophages respond with Arg-1
      enzymatic activity to M2 stimuli (IL-4/IL-13), which was further elevated in
      combination with IL-6 stimulation; however, OSM or LIF had no detectable activity
      in vitro. Arg-1 mRNA expression induced by AdOSM was attenuated in IL-6-/- and
      STAT6-/- mice, suggesting requirements for both IL-6 and IL-4/IL-13 signaling in
      vivo. Ectopic B16 tumor burden was also reduced in IL-6-/- mice. Thus, OSM
      induces Arg-1+ macrophage accumulation indirectly through elevation of Th2
      cytokines and IL-6 in vivo, whereas IL-6 acts directly on macrophages but
      requires a Th2 microenvironment, demonstrating distinct roles for OSM and IL-6 in
      M2 macrophage polarization.

PMID- 29363181
TI  - Old Medicaid Is Gone; Expanded Medicaid Is Here to Stay.

PMID- 29363183
TI  - A longitudinal study of cognitive trajectories and its factors for Koreans aged
      60 and over: A latent growth mixture model.
AB  - OBJECTIVE: The purpose of this study is twofold: first, to identify cognitive
      trajectories of older Koreans in a population-based longitudinal panel survey
      and, second, to investigate the main characteristics of the identified
      heterogeneous classes of cognitive trajectories. METHODS: Data came from 2445
      cognitively healthy persons aged 60 or older in the 2006 to 2012 Korean
      Longitudinal Study of Aging. Using Korean-mini mental status examination (K-MMSE)
      as a measure of global cognitive function, the latent growth mixture modeling
      approach examined potential heterogeneity of longitudinal changes over the 6
      years. RESULTS: This study found that older Koreans reported an average K-MMSE
      score of 27 at baseline and experienced a cognitive decline every 2 years by -1.6
      (2006-2008) and -1.2 (2008-2010), followed by a slight increase of 0.7 in 2012.
      Results from the latent growth mixture modeling analysis indicated that there
      were 2 heterogeneous classes of longitudinal changes in the K-MMSE over a period
      of 6 years: class 1 with stable cognitive function and class 2 with sharp
      cognitive decline over time. The sharp decline was found among those older in age
      and with higher level of depression at baseline. On the contrary, being male,
      higher education, active social engagement, and regular exercise were main
      characteristics of stable cognitive function. CONCLUSION: As the first to examine
      cognitive trajectories among older Koreans, this study highlighted heterogeneity
      of cognitive trajectories in the population that should be considered for
      developing differential intervention strategies aimed at both promoting healthy
      brain and delaying/preventing cognitive decline.

PMID- 29363182
TI  - Learning and memory performance following acute intranasal insulin administration
      in abstinent smokers.
AB  - The highest incidence of relapse to smoking occurs within the first 2 weeks of a
      cessation attempt. In addition to enhanced nicotine craving, this phase of
      smoking cessation is also marked by learning and memory dysfunction. Many smokers
      are not able to overcome these symptoms, and they relapse to smoking shortly
      after trying to quit. In two clinical studies, we evaluated intranasal insulin
      for efficacy in improving learning and memory function during nicotine
      withdrawal. Our first study was a crossover evaluation (N = 19) following 20 hr
      of smoking abstinence. Study 2 was a parallel design study (N = 50) following 16
      hr of abstinence. Intranasal insulin (60 IU) dose was administered in both
      studies and cognitive function was measured using California Verbal Learning Test
      II. Intranasal insulin did not improve learning over the 5 verbal learning
      trials. In addition, intranasal insulin did not improve either short- or long
      delay recall in either study. In summary, the one-time administration of
      intranasal insulin does not improve verbal learning and memory in smokers.
      Whether longer administration schedules may be of benefit should be evaluated in
      future studies.

PMID- 29363184
TI  - Functional differences in airway dendritic cells determine susceptibility to IgE
      sensitization.
AB  - Respiratory IgE-sensitization to innocuous antigens increases the risk for
      developing diseases such as allergic asthma. Dendritic cells (DC) residing in the
      airways orchestrate the immune response following antigen exposure and their
      ability to sample and present antigens to naive T cells in airway draining lymph
      nodes contributes to allergen-specific IgE-sensitization. In order to
      characterize inhaled antigen capture and presentation by DC subtypes in vivo, we
      used an adjuvant-free respiratory sensitization model using two genetically
      distinct rat strains, one of which is naturally resistant and the other naturally
      susceptible to allergic sensitization. Upon multiple exposures to ovalbumin
      (OVA), the susceptible strain developed OVA-specific IgE and airway inflammation,
      whereas the resistant strain did not. Using fluorescently tagged OVA and flow
      cytometry, we demonstrated significant differences in antigen uptake efficiency
      and presentation associated with either IgE-sensitization or resistance to
      allergen exposures in respective strains. We further identified CD4+ conventional
      DC (cDC) as the subset involved in airway antigen sampling in both strains,
      however, CD4+ cDC in the susceptible strain were less efficient in OVA sampling
      and displayed increased MHC-II expression compared with the resistant strain.
      This was associated with generation of an exaggerated Th2 response and a
      deficiency of airway regulatory T cells in the susceptible strain. These data
      suggest that subsets of cDC are able to induce either sensitization or resistance
      to inhaled antigens as determined by genetic background, which may provide an
      underlying basis for genetically determined susceptibility to respiratory
      allergic sensitization and IgE production in susceptible individuals.

PMID- 29363185
TI  - Differential signaling pathways are initiated in macrophages during infection
      depending on the intracellular fate of Chlamydia spp.
AB  - Chlamydia muridarum and Chlamydia caviae have equivalent growth rates in mouse
      epithelial cells but only C. muridarum replicates inside mouse macrophages, while
      C. caviae does not. Macrophages infected with C. muridarum or C. caviae were used
      to address the hypothesis that the early signaling pathways initiated during
      infection depend on the fate of chlamydiae in the host cell. Transmission
      electron microscopy of C. muridarum-infected macrophages showed intact chlamydial
      elementary bodies and reticulate bodies 2 h postinfection in compact vacuoles.
      Conversely, in macrophages infected with C. caviae, chlamydiae were observed in
      large phagocytic vacuoles. Furthermore, C. caviae infections failed to develop
      into inclusions or produce viable bacteria. Expression of proinflammatory
      cytokines TNFalpha, IL-1beta and MMP13 was similar in C. caviae- or C. muridarum
      infected macrophages at 3 h postinfection, indicating that chlamydial survival is
      not required for initiation of these responses. IL-1beta secretion, dependent on
      inflammasome activation, occurred in C. caviae-infected macrophages despite no
      chlamydial growth. Conversely, IFNbeta mRNA was observed only in C. muridarum-
      but not in C. caviae-infected macrophages. These data demonstrate that
      differential signaling events are initiated during a productive versus
      nonproductive chlamydial infection in a macrophage.

PMID- 29363186
TI  - Integrated decision strategies for skin sensitization hazard.

PMID- 29363187
TI  - GPR65 inhibits experimental autoimmune encephalomyelitis through CD4+ T cell
      independent mechanisms that include effects on iNKT cells.
AB  - The G protein-coupled receptor 65 (GPR65) gene has been genetically associated
      with several autoimmune diseases, including multiple sclerosis (MS). GPR65 is
      predominantly expressed in lymphoid organs and is activated by extracellular
      protons. In this study, we tested whether GPR65 plays a functional role in
      demyelinating autoimmune disease. Using a murine model of MS, experimental
      autoimmune encephalomyelitis (EAE), we found that Gpr65-deficient mice develop
      exacerbated disease. CD4+ helper T cells are key drivers of EAE pathogenesis,
      however, Gpr65 deficiency in these cells did not contribute to the observed
      exacerbated disease. Instead, Gpr65 expression levels were found to be highest on
      invariant natural killer T (iNKT) cells. EAE severity in Gpr65-deficient mice was
      normalized in the absence of iNKT cells (CD1d-deficient mice), suggesting that
      GPR65 signals in iNKT cells are important for suppressing autoimmune disease.
      These findings provide functional support for the genetic association of GPR65
      with MS and demonstrate GPR65 signals suppress autoimmune activity in EAE.

PMID- 29363188
TI  - Interaction between the sequence of feeding of hay and concentrate, and boiling
      of barley on feed intake, the activity of hydrolytic enzymes and fermentation in
      the hindgut of Arabian mares.
AB  - The interaction between the sequence of feeding of hay and concentrate and the
      hydrothermal processing of barley in alleviating concentrate effects on intake,
      and hindgut fermentation in horses was tested. Six Arabian mares (4-10 years of
      age, 410 +/- 35 kg body weight) were used to evaluate the effects of feeding
      sequence (FS) and type of barley (TB) on intake, and faecal volatile fatty acids
      (VFA), activities of alpha-amylase (AA: EC 3.2.1.1), carboxymethyl cellulase
      (CMCase: EC 3.2.1.4), microcrystalline cellulase (MCCase: EC 3.2.1.91) and
      general filter paper degrading activity (FPD). Mares were offered a ration of air
      dried alfalfa and concentrate (70:30 as-fed) in four subsequent periods of 14
      days including 8 days of adaptation and 6 days of sampling. In each period and
      each meal, mares received concentrate either 30 min after (HC) or 30 min before
      (CH) alfalfa hay. Barley was either milled or boiled in water. Rectal samples
      were grabbed directly from rectum once per period. Mares subjected to CH had
      higher dry matter intakes than mares under HC regime. The acetate:propionate
      ratio (A:P ratio) in rectal content was higher with CH than HC. The AA activity
      was higher under CH than under HC. Mares fed boiled barley had lower rectal
      concentrations of VFA and propionate and a higher A:P ratio than mares fed milled
      barley. Furthermore, the rectal content showed a higher MCCase activity but a
      lower AA activity when mares were fed boiled compared with milled barley.
      Interactions between FS and TB were observed with respect to CMCase activity, and
      concentrations of propionate and valerate. In conclusion, the present results
      suggest that both, feeding concentrate before hay and boiling the barley, might
      improve the hindgut environment in Arabian mares, and that the two measures were
      mostly additive and sometimes even synergistic.

PMID- 29363189
TI  - Synergism of Geometric Construction and Electronic Regulation: 3D Se-(NiCo)Sx
      /(OH)x Nanosheets for Highly Efficient Overall Water Splitting.
AB  - The exploration of highly efficient electrocatalysts for both oxygen and hydrogen
      generation via water splitting is receiving considerable attention in recent
      decades. Up till now, Pt-based catalysts still exhibit the best hydrogen
      evolution reaction (HER) performance and Ir/Ru-based oxides are identified as the
      benchmark for oxygen evolution reaction (OER). However, the high cost and rarity
      of these materials extremely hinder their large-scale applications. This paper
      describes the construction of the ultrathin defect-enriched 3D Se-(NiCo)Sx /(OH)x
      nanosheets for overall water splitting through a facile Se-induced hydrothermal
      treatment. Via Se-induced fabrication, highly efficient Se-(NiCo)Sx /(OH)x
      nanosheets are successfully fabricated through morphology optimization, defect
      engineering, and electronic structure tailoring. The as-prepared hybrids exhibit
      relatively low overpotentials of 155 and 103 mV at the current density of 10 mA
      cm-2 for OER and HER, respectively. Moreover, an overall water-splitting device
      delivers a current density of 10 mA cm-2 for ~66 h without obvious degradation.

PMID- 29363190
TI  - Effect of feeding Acacia nilotica pods to sheep on nutrient digestibility,
      nitrogen balance, ruminal protozoa and rumen enzymes activity.
AB  - This study was conducted to evaluate the effect of supplying two levels of Acacia
      nilotica (A. nilotica) pods to rations of sheep on nutrient digestibility,
      nitrogen balance and rumen liquor parameters (pH, total protozoa count, protein
      concentration and enzymes activity). Twelve mature rams (50 +/- 1.25 kg B.W.)
      were distributed into three groups, each with four rams. Animals in group one
      were considered as a control which fed a basal diet, consisting of concentrate
      mixture and Egyptian clover. The second group and the third one received the same
      basal diet with supplying the concentrate mixture by 1.5% and 3.0% of A. nilotica
      pods meal respectively. The experiment lasted for 3 weeks. It was found that
      supplementation of A. nilotica pods to the concentrate mixture at a rate of 1.5%
      and 3.0% significantly improved the total feed intake compared to the control.
      The digestibility of dry matter and crude fibre was significantly reduced with A.
      nilotica supplements, whereas the digestibility of crude protein was
      significantly improved. All of nitrogen intake and N-retained were significantly
      increased in rams fed on concentrates with 1.5% and 3.0% A.  nilotica pods when
      compared to the control. The pH of ruminal fluid was not affected by the dietary
      treatments. Nevertheless, the total rumen protozoa count was significantly
      decreased in A. nilotica pods supplemented groups. Also, the rumen protein
      concentration and the ruminal enzymes activity, especially alpha-amylase,
      cellulase and protease, were lower in A. nilotica pods supplemented treatments.
      In conclusions, inclusion of low levels of A. nilotica pods (1.5% and 3.0%) in
      the concentrates can be used as a natural protein protectant in ruminants by
      forming tannin protein complexes in the rumen to maximize the amino acids
      available in the lower digestive tract. Also, these levels can increase the
      protein digestibility as well as the N-retained in the body .

PMID- 29363191
TI  - Investigation of the binding characteristics between ligands and epidermal growth
      factor receptor by cell membrane chromatography.
AB  - The binding property between a ligand and its receptor is very important for
      numerous biological processes. In this study, we developed a high epidermal
      growth factor receptor (EGFR)-expression cell membrane chromatography (CMC)
      method to investigate the binding characteristics between EGFR and the ligands
      gefitinib, erlotinib, canertinib, afatinib, and vandetanib. Competitive binding
      analysis using gefitinib as the marker was used to investigate the interactions
      that occurred at specific binding sites on EGFR. The ability of displacement was
      measured from the HEK293-EGFR/CMC column on the binding sites occupied by
      gefitinib for these ligands, which revealed the following order: gefitinib (KD,
      8.49 +/- 0.11 * 10-7  M) > erlotinib (KD, 1.07 +/- 0.02 * 10-6  M) > canertinib
      (KD, 1.41 +/- 0.07 * 10-6  M) > afatinib (KD, 1.80 +/- 0.12 * 10-6  M) >
      vandetanib (KD, 1.99 +/- 0.03 * 10-6  M). This order corresponded with the values
      estimated by frontal displacement analysis and the scores obtained with molecular
      docking. Furthermore, thermodynamic analysis indicated that the hydrogen bond or
      Van der Waals force was the main interaction force in the process of EGFR binding
      to all 5 ligands. Overall, these results demonstrate that a CMC method could be
      an effective tool to investigate the binding characteristics between ligands and
      receptors.

PMID- 29363192
TI  - Plasticity effect of rider-horse interaction on genetic evaluations for Show
      Jumping discipline in sport horses.
AB  - To obtain a sport horse that excels in the highest levels of competition,
      breeders must take into account certain genetic and environmental factors that
      could influence the sport horse's performance, such as the rider-horse
      interaction (RHI). The main aim of this study was to describe this interaction in
      a genetic model by modelling it in relation to the horse's age. A total of 31,129
      sport results from Spanish Sport Horses were used from a total of 1,101 animals
      evaluated, and these were grouped in three age levels and had been ridden by 606
      different riders. Only riders who had ridden more than one horse (and vice-versa)
      were considered for the analyses. Five linear models with different random
      effects were analysed according to the covariates, the homogeneity/heterogeneity
      of the RHI and the relevant residual random effects. The model of best fit was
      then selected for the genetic evaluation of the animal. In general, models
      including the RHI effect (M2, M4 and M5) fitted better than the other models, and
      the best fit was obtained for M4 (with heterogeneous residual variance). The
      genetic variance increased constantly with age, whereas heritability showed a
      response on three intervals. This study revealed the varied evolution of the RHI
      with age, showing the different "plastic abilities" of this relationship.

PMID- 29363193
TI  - Cell shortening and calcium dynamics in epicardial and endocardial myocytes from
      the left ventricle of Goto-Kakizaki type 2 diabetic rats.
AB  - NEW FINDINGS: What is the central question of this study? To investigate
      haemodynamic dysfunction in the type 2 diabetic Goto-Kakizaki (GK) rat, we
      measured shortening and Ca2+ transport in ventricular myocytes from epicardial
      (EPI) and endocardial (ENDO) regions. What is the main finding and its
      importance? EPI and ENDO GK myocytes displayed similar hypertrophy. Time to peak
      (TPK) and time to half (THALF) relaxation were prolonged in EPI GK myocytes. TPK
      Ca2+ transient was prolonged and THALF decay of the Ca2+ transient was shortened
      in EPI GK myocytes. Amplitude of shortening, Ca2+ transient and sarcoplasmic
      reticulum Ca2+ were unaltered in EPI and ENDO myocytes from Goto-Kakizaki
      compared with control rats. We demostrated regional differences in shortening and
      Ca2+ transport in Goto-Kakizaki rats. ABSTRACT: Diabetic cardiomyopathy is
      considered to be one of the major diabetes-associated complications, and the
      pathogenesis of cardiac dysfunction is not well understood. The electromechanical
      properties of cardiac myocytes vary across the walls of the chambers. The aim of
      this study was to investigate shortening and Ca2+ transport in epicardial (EPI)
      and endocardial (ENDO) left ventricular myocytes in the Goto-Kakizaki (GK) type 2
      diabetic rat heart. Shortening and intracellular Ca2+ transients were measured by
      video edge detection and fluorescence photometry. Myocyte surface area was
      increased in EPI-GK and ENDO-GK compared with control EPI-CON and ENDO-CON
      myocytes. Time to peak shortening was prolonged in EPI-GK compared with EPI-CON
      and in ENDO-CON compared with EPI-CON myocytes. Time to half-relaxation of
      shortening and time to peak Ca2+ transient were prolonged in EPI-GK compared with
      EPI-CON myocytes. Time to half-decay of the Ca2+ transient was prolonged in EPI
      CON compared with EPI-GK and in EPI-CON compared with ENDO-CON myocytes. The
      amplitude of shortening and the Ca2+ transient were unaltered in EPI-GK and ENDO
      GK compared with their respective controls. Sarcoplasmic reticulum Ca2+ and
      myofilament sensitivity to Ca2+ were unaltered in EPI-GK and ENDO-GK compared
      with their respective controls. Regional differences in Ca2+ signalling in
      healthy and diabetic myocytes might account for variation in the dynamics of
      myocyte shortening. Further studies will be required to clarify the mechanisms
      underlying regional differences in the time course of shortening and the Ca2+
      transient in EPI and ENDO myocytes from diabetic and control hearts.

PMID- 29363194
TI  - Crystallographic Orientation Dependent Reactive Ion Etching in Single Crystal
      Diamond.
AB  - Sculpturing desired shapes in single crystal diamond is ever more crucial in the
      realization of complex devices for nanophotonics, quantum computing, and quantum
      optics. The crystallographic orientation dependent wet etch of single crystalline
      silicon in potassium hydroxide (KOH) allows a range of shapes to be formed and
      has significant impacts on microelectromechanical systems (MEMS), atomic force
      microscopy (AFM), and microfluidics. Here, a crystal direction dependent dry
      etching principle in an inductively coupled plasma reactive ion etcher is
      presented, which selectively reveals desired crystal planes in monocrystalline
      diamond by controlling the etching conditions. Using this principle, monolithic
      diamond nanopillars for magnetometry using nitrogen vacancy centers are
      fabricated. In these nanopillars, a half-tapering angle up to 21 degrees  is
      achieved, the highest angle reported in the literature, which leads to a high
      photon efficiency and high mechanical strength of the nanopillar. These results
      represent the first demonstration of a crystallographic orientation dependent
      reactive ion etching principle, which opens a new window for shaping specific
      nanostructures which is at the heart of nanotechnology. It is believed that this
      principle will prove to be valuable for the structuring and patterning of other
      single crystal materials as well.

PMID- 29363195
TI  - Is frequency of family meals associated with fruit and vegetable intake among
      preschoolers? A logistic regression analysis.
AB  - BACKGROUND: The present study aimed to examine the associations between frequency
      of family meals and low fruit and vegetable intake in preschool children.
      Promoting healthy nutrition early in life is recommended for combating childhood
      obesity. Frequency of family meals is associated with fruit and vegetable intake
      in school-age children and adolescents; the relationship in young children is
      less clear. METHODS: We completed a secondary analysis using data from the Early
      Childhood Longitudinal Study-Birth Cohort. Participants included children, born
      in the year 2001, to mothers who were >15 years old (n = 8 950). Data were
      extracted from structured parent interviews during the year prior to
      kindergarten. We used hierarchical logistic regression to describe the
      relationships between frequency of family meals and low fruit and vegetable
      intake. RESULTS: Frequency of family meals was associated with low fruit and
      vegetable intake. The odds of low fruit and vegetable intake were greater for
      preschoolers who shared less than three evening family meals per week (odds ratio
      = 1.5, beta = 0.376, P < 0.001) than preschoolers who shared the evening meal
      with family every night. CONCLUSIONS: Fruit and vegetable intake is related to
      frequency of family meals in preschool-age children. Educating parents about the
      potential benefits of frequent shared meals may lead to a higher fruit and
      vegetable consumption among preschoolers. Future studies should address other
      factors that likely contribute to eating patterns during the preschool years.

PMID- 29363196
TI  - Regulation of sporangium formation by the orphan response regulator TcrA in the
      rare actinomycete Actinoplanes missouriensis.
AB  - The rare actinomycete Actinoplanes missouriensis forms terminal sporangia
      containing a few hundred flagellated spores, which can swim in aquatic
      environments after release from sporangium. However, gene regulation for its
      characteristic morphological development is largely unknown. Here, we report the
      functional analysis of an orphan response regulator, TcrA, which is encoded next
      to the chemotaxis-flagellar gene cluster. The tcrA null (DeltatcrA) mutant formed
      sporangium, in which sporulation proceeded. However, many distorted spores were
      produced and some spores ectopically germinated in the mutant sporangia. In
      addition, spores were hardly released from the mutant sporangia. A comparative
      RNA-Seq analysis between the wild-type and DeltatcrA strains showed that TcrA
      upregulated the transcription of more than 263 genes, which were integrated into
      185 transcriptional units. In silico searches identified a 21-bp direct repeat
      sequence, 5'-nnGCA(A/C)CCG-n4 -GCA(A/C)CCGn-3', as the TcrA box, which was
      confirmed by electrophoretic mobility shift assays. Finally, we identified 34
      transcriptional units as the TcrA regulon. TcrA seems to regulate a few hundred
      genes through the transcriptional activation of three FliA-family sigma factor
      genes besides its own regulon. We concluded that TcrA is a global transcriptional
      activator that controls many aspects of sporangium formation, including flagellar
      biogenesis, spore dormancy and sporangium dehiscence.

PMID- 29363197
TI  - Defect Effects on TiO2 Nanosheets: Stabilizing Single Atomic Site Au and
      Promoting Catalytic Properties.
AB  - Isolated single atomic site catalysts have attracted great interest due to their
      remarkable catalytic properties. Because of their high surface energy, single
      atoms are highly mobile and tend to form aggregate during synthetic and catalytic
      processes. Therefore, it is a significant challenge to fabricate isolated single
      atomic site catalysts with good stability. Herein, a gentle method to stabilize
      single atomic site metal by constructing defects on the surface of supports is
      presented. As a proof of concept, single atomic site Au supported on defective
      TiO2 nanosheets is prepared and it is discovered that (1) the surface defects on
      TiO2 nanosheets can effectively stabilize Au single atomic sites through forming
      the Ti-Au-Ti structure; and (2) the Ti-Au-Ti structure can also promote the
      catalytic properties through reducing the energy barrier and relieving the
      competitive adsorption on isolated Au atomic sites. It is believed that this work
      paves a way to design stable and active single atomic site catalysts on oxide
      supports.

PMID- 29363198
TI  - Multifunctional Photonic Nanomaterials for Diagnostic, Therapeutic, and
      Theranostic Applications.
AB  - The last decade has seen dramatic progress in the principle, design, and
      fabrication of photonic nanomaterials with various optical properties and
      functionalities. Light-emitting and light-responsive nanomaterials, such as
      semiconductor quantum dots, plasmonic metal nanoparticles, organic carbon, and
      polymeric nanomaterials, offer promising approaches to low-cost and effective
      diagnostic, therapeutic, and theranostic applications. Reasonable endeavors have
      begun to translate some of the promising photonic nanomaterials to the clinic.
      Here, current research on the state-of-the-art and emerging photonic
      nanomaterials for diverse biomedical applications is reviewed, and the remaining
      challenges and future perspectives are discussed.

PMID- 29363199
TI  - Diets with a low glycaemic load have favourable effects on prediabetes
      progression and regression: a prospective cohort study.
AB  - BACKGROUND: To date, no study assessing the associations among glycaemic index
      (GI), glycaemic load (GL) and progression to diabetes has focused specifically on
      prediabetes. Moreover, the available data on the association between these
      variables and regression to normal glucose regulation (NGR) are insufficient.
      Therefore, the present study aimed to evaluate the longitudinal associations
      among GI, GL and prediabetes outcomes. METHODS: This prospective study included
      640 adults aged 40-79 years with prediabetes at baseline. Dietary data were
      assessed using a previously validated 3-day food record. The participants were
      divided into three groups according to GI and GL tertiles. Outcomes were defined
      based on annual oral glucose tolerance test results. RESULTS: During a median of
      5 years of follow-up, 127 incident cases of diabetes and 249 incident cases of
      NGR were identified. Dietary GL was positively associated with the risk of
      developing diabetes and negatively associated with the likelihood of reaching NGR
      at least once. Comparing the highest and lowest tertiles of GL, the multivariable
      adjusted hazard ratios (95% confidence intervals) were 1.85 (1.07-3.21) for
      progression and 0.65 (0.44-0.96) for regression. No association was observed
      between GI and prediabetes outcomes in the fully adjusted models. CONCLUSIONS:
      Among patients with prediabetes, high dietary GL was positively associated with
      diabetes risk. Furthermore, a low-GL diet contributed to an increased incidence
      of reaching NGR.

PMID- 29363200
TI  - Optogenetically enhanced axon regeneration: motor versus sensory neuron-specific
      stimulation.
AB  - Brief neuronal activation in injured peripheral nerves is both necessary and
      sufficient to enhance motor axon regeneration, and this effect is specific to the
      activated motoneurons. It is less clear whether sensory neurons respond in a
      similar manner to neuronal activation following peripheral axotomy. Further, it
      is unknown to what extent enhancement of axon regeneration with increased
      neuronal activity relies on a reflexive interaction within the spinal circuitry.
      We used mouse genetics and optical tools to evaluate the precision and
      selectivity of system-specific neuronal activation to enhance axon regeneration
      in a mixed nerve. We evaluated sensory and motor axon regeneration in two
      different mouse models expressing the light-sensitive cation channel,
      channelrhodopsin (ChR2). We selectively activated either sensory or motor axons
      using light stimulation combined with transection and repair of the sciatic
      nerve. Regardless of genotype, the number of ChR2-positive neurons whose axons
      had regenerated successfully was greater following system-specific optical
      treatment, with no effect on the number of ChR2-negative neurons (whether motor
      or sensory neurons). We conclude that acute system-specific neuronal activation
      is sufficient to enhance both motor and sensory axon regeneration. This
      regeneration-enhancing effect is likely cell autonomous.

PMID- 29363201
TI  - Response to "A concern with the clinical consensus guidelines on meticillin
      resistant staphylococci," a letter in Veterinary Dermatology 2018; 29: 174.

PMID- 29363202
TI  - Achieving Skeletal Diversity in Peptide Macrocycles through The Use of
      Heterocyclic Grafts.
AB  - Despite their therapeutic potential, peptide macrocycles often suffer from
      drawbacks such as low membrane permeability, proteolytic instability, and
      conformational lability. As a result, there have been significant efforts to
      "depeptidize" amino acid-rich macrocycles through the incorporation of
      heterocyclic grafts into their backbones. In this concept article, we summarize
      selected recent methodologies that can be used to introduce heterocycles into
      cyclic peptides.

PMID- 29363203
TI  - N-C Axially Chiral Anilines: Electronic Effect on Barrier to Rotation and A
      Remote Proton Brake.
AB  - N-Aryl-N-methyl-2-tert-butyl-6-methylaniline derivatives exhibit a rotationally
      stable N-C axially chiral structure and the rotational barriers around an N-C
      chiral axis increased with the increase in electron-withdrawing character of para
      substituent on the aryl group. X-ray crystal structural analysis and the DFT
      calculation suggested that the considerable change of the rotational barriers by
      the electron effect of para-substituents is due to the disappearance of resonance
      stabilization energy caused by the twisting of para-substituted phenyl group in
      the transition state. This structural property of the N-C axially chiral anilines
      was employed to reveal a new acid-decelerated molecular rotor caused by the
      protonation at the remote position (remote proton brake).

PMID- 29363204
TI  - Defining a Materials Database for the Design of Copper Binary Alloy Catalysts for
      Electrochemical CO2 Conversion.
AB  - While Cu electrodes are a versatile material in the electrochemical production of
      desired hydrocarbon fuels, Cu binary alloy electrodes are recently proposed to
      further tune reaction directionality and, more importantly, overcome the
      intrinsic limitation of scaling relations. Despite encouraging empirical
      demonstrations of various Cu-based metal alloy systems, the underlying principles
      of their outstanding performance are not fully addressed. In particular, possible
      phase segregation with concurrent composition changes, which is widely observed
      in the field of metallurgy, is not at all considered. Moreover, surface-exposed
      metals can easily form oxide species, which is another pivotal factor that
      determines overall catalytic properties. Here, the understanding of Cu binary
      alloy catalysts for CO2 reduction and recent progress in this field are
      discussed. From the viewpoint of the thermodynamic stability of the alloy system
      and elemental mixing, possible microstructures and naturally generated surface
      oxide species are proposed. These basic principles of material science can help
      to predict and understand metal alloy structure and, moreover, act as an
      inspiration for the development of new binary alloy catalysts to further improve
      CO2 conversion and, ultimately, achieve a carbon-neutral cycle.

PMID- 29363205
TI  - Endowing Perovskite Nanocrystals with Circularly Polarized Luminescence.
AB  - Perovskite nanocrystals are attracting great interest due to their excellent
      photonic properties. Here, through a supramolecular self-assembly approach, the
      perovskite nanocrystals (NCs) with a novel circularly polarized luminescence
      (CPL) are successfully endowed. It is found that the achiral perovskite NCs can
      coassemble with chiral gelator in nonpolar solvents, in which the gelator
      molecules modify the surface of the perovskite NCs. Through such cogelation, the
      molecular chirality can transfer to the NCs resulting in CPL signals with a
      dissymmetric factor (glum ) up to 10-3 . Furthermore, depending on the molecular
      chirality of the gelator, the CPL sense can be selected and the mirror-imaged CPL
      is obtained. Such gels can be further embedded into the polymer film to
      facilitate flexible CPL devices. It is envisaged that this approach will afford a
      new insight into the designing of the functional chiroptical materials.

PMID- 29363206
TI  - Boryl- and Silyl-Substituted Mixed Sandwich Compounds of Scandium.
AB  - An improved, one-pot synthesis of the linear sandwich compound [Sc(eta5 -C5 H5
      )(eta8 -C8 H8 )] is presented. The synthetic procedure is amenable to boryl- and
      silyl-substituted cyclopentadienyl and cyclooctatetraenyl ligands, thereby
      yielding the first functionalized derivatives. We found that the synthesis of the
      silyl-substituted mixed sandwich complexes produces higher yields when the ligand
      exchange is carried out stepwise, by isolating the intermediate
      trimethylsilylated half-sandwich complex [Sc(eta8 -C8 H7 SiMe3 )Cl(THF)]
      (THF=tetrahydrofuran). The molecular structures of the parent complex, as well as
      of its mono-boryl-substituted derivatives, have been determined by single-crystal
      X-ray diffraction. In addition, the optical and electrochemical properties of the
      mixed sandwich complexes are reported.

PMID- 29363207
TI  - Heterogeneous effects of M-CSF isoforms on the progression of MLL-AF9 leukemia.
AB  - Macrophage colony-stimulating factor (M-CSF) regulates both malignant cells and
      microenvironmental cells. Its splicing isoforms show functional heterogeneity.
      However, their roles on leukemia have not been well established. Here, the
      expression of total M-CSF in patients with hematopoietic malignancies was
      analyzed. The roles of M-CSF isoforms on the progression of acute myeloid
      leukemia (AML) were studied by establishing MLL-AF9-induced mouse AML models with
      high level membrane-bound M-CSF (mM-CSF) or soluble M-CSF (sM-CSF). Total M-CSF
      was highly expressed in myeloid leukemia patients. Furthermore, mM-CSF but not sM
      CSF prolonged the survival of leukemia mice. While sM-CSF was more potent to
      promote proliferation and self-renew, mM-CSF was more potent to promote
      differentiation. Moreover, isoforms had different effects on leukemia-associated
      macrophages (LAMs) though they both increase monocytes/macrophages by growth
      promoting and recruitment effects. In addition, mM-CSF promoted specific
      phagocytosis of leukemia cells by LAMs. RNA-seq analysis revealed that mM-CSF
      enhanced phagocytosis-associated genes and activated oxidative phosphorylation
      and metabolism pathway. These results highlight heterogeneous effects of M-CSF
      isoforms on AML progression and the mechanisms of mM-CSF, that is, intrinsically
      promoting AML cell differentiation and extrinsically enhancing infiltration of
      macrophages and phagocytosis by macrophages, which may provide potential clues
      for clinical diagnosis and therapy.

PMID- 29363208
TI  - Thermal-Responsive Polymers for Enhancing Safety of Electrochemical Storage
      Devices.
AB  - Thermal runway constitutes the most pressing safety issue in lithium-ion
      batteries and supercapacitors of large-scale and high-power density due to risks
      of fire or explosion. However, traditional strategies for averting thermal
      runaway do not enable the charging-discharging rate to change according to
      temperature or the original performance to resume when the device is cooled to
      room temperature. To efficiently control thermal runaway, thermal-responsive
      polymers provide a feasible and reversible strategy due to their ability to sense
      and subsequently act according to a predetermined sequence when triggered by
      heat. Herein, recent research progress on the use of thermal-responsive polymers
      to enhance the thermal safety of electrochemical storage devices is reviewed.
      First, a brief discussion is provided on the methods of preventing thermal
      runaway in electrochemical storage devices. Subsequently, a short review is
      provided on the different types of thermal-responsive polymers that can
      efficiently avoid thermal runaway, such as phase change polymers, polymers with
      sol-gel transitions, and polymers with positive temperature coefficients. The
      results represent the important development of thermal-responsive polymers toward
      the prevention of thermal runaway in next-generation smart electrochemical
      storage devices.

PMID- 29363209
TI  - A concern with the clinical consensus guidelines on meticillin-resistant
      staphylococci.

PMID- 29363210
TI  - In vitro antimicrobial activity of narasin against common clinical isolates
      associated with canine otitis externa.
AB  - BACKGROUND: Antimicrobial resistance and antimicrobial stewardship are of ever
      increasing importance in veterinary medicine. Re-purposing of old drugs that are
      not used in human medicine is one approach that addresses the emergence of
      multidrug resistance in canine skin and ear infections, and can reduce the use of
      critically important human antibiotic classes. HYPOTHESIS/OBJECTIVES: To
      determine the antimicrobial activity of narasin, a polyether ionophore
      conventionally used as a rumen modifier and anticoccidial agent in production
      animals, against common clinical isolates of canine otitis externa (OE).
      ANIMALS/ISOLATES: Clinical isolates (n = 110) from canine OE were tested,
      including 17 meticillin-susceptible Staphylococcus pseudintermedius (MSSP), 13
      multidrug-resistant Staphylococcus pseudintermedius (MDRSP), and 20 each of beta
      haemolytic Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis and
      Malassezia pachydermatis. METHODS: Bacterial and yeast isolates were subcultured,
      suspended in broth and inoculated into 96-well plates. Organisms were tested
      against concentrations of narasin ranging from 0.03 to 128 MUg/mL. Minimal
      inhibitory concentrations (MICs) were determined after overnight incubation.
      RESULTS: Narasin MICs for staphylococcal and streptococcal isolates ranged from
      0.06 to 0.25 MUg/mL; MIC50 and MIC90 values for both organisms were 0.125 MUg/mL.
      No MICs were achieved for Pseudomonas or Proteus isolates. There was a weak
      antifungal effect against M. pachydermatis isolates (MIC 32 to >128 MUg/mL).
      CONCLUSIONS AND CLINICAL RELEVANCE: Narasin was effective against Gram-positive
      bacteria and had antifungal activity at higher concentrations against M.
      pachydermatis. However, the lack of Gram-negative activity would prevent its use
      as a sole antimicrobial agent in cases of canine OE.

PMID- 29363211
TI  - Low prevalence of mupirocin resistance in Staphylococcus pseudintermedius
      isolates from canine pyoderma in Korea.
AB  - BACKGROUND: Mupirocin is a topical antibacterial drug used for the treatment of
      staphylococcal infections, including meticillin-resistant Staphylococcus
      pseudintermedius (MRSP). The recent emergence of resistance to mupirocin is a
      major concern in many countries. OBJECTIVES: This study investigated the
      prevalence and genotype of mupirocin-resistant S. pseudintermedius isolated from
      pet dogs with pyoderma. SAMPLES: A total of 110 clinical isolates of S.
      pseudintermedius were collected from dogs with pyoderma (n = 110) between July
      2010 and September 2016. All animals were client-owned dogs. METHODS: Low- and
      high-level mupirocin resistance were evaluated with both the broth microdilution
      and disk diffusion tests. Mupirocin resistance in S. pseudintermedius isolates
      was confirmed by genetic analysis of the ileS-2 and naive ileS genes. RESULTS:
      MRSP and meticillin-susceptible S. pseudintermedius were detected in 69 and 41
      dogs, respectively. One MRSP strain was highly resistant to mupirocin and
      contained the high-level mupirocin resistance gene ileS-2. There were no low
      level mupirocin-resistant isolates. CONCLUSION AND CLINICAL IMPORTANCE: Mupirocin
      is a useful topical antibacterial for MRSP, but a clinical MRSP isolate that had
      not previously been exposed to mupirocin exhibited the high-level mupirocin
      resistance in phenotype and genotype. Therefore, continuous monitoring for
      mupirocin resistance is important in small animal practice.

PMID- 29363212
TI  - Photoredox-Based Actuation of an Artificial Molecular Muscle.
AB  - The use of light to actuate materials is advantageous because it represents a
      cost-effective and operationally straightforward way to introduce energy into a
      stimuli-responsive system. Common strategies for photoinduced actuation of
      materials typically rely on light irradiation to isomerize azobenzene or
      spiropyran derivatives, or to induce unidirectional rotation of molecular motors
      incorporated into a 3D polymer network. Although interest in photoredox catalysis
      has risen exponentially in the past decade, there are far fewer examples where
      photoinduced electron transfer (PET) processes are employed to actuate materials.
      Here, a novel mode of actuation in a series of redox-responsive hydrogels doped
      with a visible-light-absorbing ruthenium-based photocatalyst is reported. The
      hydrogels are composed primarily of polyethylene glycol and low molar
      concentrations of a unimolecular electroactive polyviologen that is activated
      through a PET mechanism. The rate and degree of contraction of the hydrogels are
      measured over several hours while irradiating with blue light. Likewise, the
      change in mechanical properties-determined through oscillatory shear rheology
      experiments-is assessed as a function of polyviologen concentration. Finally, an
      artificial molecular muscle is fabricated using the best-performing hydrogel
      composition, and its ability to perform work, while irradiated, is demonstrated
      by lifting a small weight.

PMID- 29363213
TI  - Ultrasonographic and computed tomographic features of rice bodies in an Arabian
      horse with atlantal bursitis.
AB  - A 19-year-old castrated Arabian male horse presented for evaluation of a firm
      mass at the dorsal cervical region. Ultrasonography and computed tomography
      revealed multiple well defined fusiform structures within the atlantal bursa.
      Multiple glossy smooth, white to yellowish, flattened fusiform structures were
      removed surgically. These structures were composed of dense fibrin with some
      leukocytes and red blood cells. The imaging and histopathological features of
      these structures were similar to chronic 'rice bodies' reported in humans with
      bursitis or tenosynovitis. This is the first veterinary report describing the
      imaging features of 'rice bodies' in a horse with atlantal bursitis.

PMID- 29363214
TI  - Radiographic findings and clinical factors in dogs with surgically confirmed or
      presumed colonic torsion.
AB  - Colonic torsion is a life-threatening condition in dogs and radiographic findings
      for this condition have not been well described. The purpose of this
      retrospective case series was to describe radiographic findings and clinical
      signs in a group of dogs with colonic torsion. Inclusion criteria were dogs
      presenting during the period of 2006 and 2016, and that had abdominal radiography
      and a surgically confirmed or presumed diagnosis of colonic torsion. For each
      dog, clinical data were recorded from medical records and imaging findings were
      recorded from retrieved plain radiographs and positive contrast radiographs in
      which barium enema was performed. Fourteen dogs met inclusion criteria. Of these,
      nine dogs had colonic torsion confirmed at surgery, with five dogs having
      surgical confirmation of colonic congestion or mesenteric torsion. Radiographic
      findings included segmental distention of the colon (14/14), focal narrowing of
      the colon (11/14), displacement of cecum (11/14), displacement of descending
      colon (14/14), and mild to no small intestinal distention (14/14). In cases where
      barium enema was performed, focal narrowing of the colon and longitudinal
      striations that course in a helical pattern were identified, termed the "torsion
      sign." Vomiting was the most common clinical sign observed (12/14), followed by
      abdominal pain in a small majority of cases (8/14). Severe abdominal pain and
      hypovolemic shock were uncommon in the patients reported (3/14). Colonic torsion
      should be considered as a differential diagnosis for dogs with radiographic
      segmental colonic distention with displacement of the descending colon and cecum.
      Barium enema is recommended for more definitive diagnosis.

PMID- 29363215
TI  - Anaphylaxis to packaged foods in Australasia.
AB  - AIMS: To examine reports of anaphylaxis in Australasia from consumption of
      packaged food products with or without precautionary allergen labelling (PAL),
      where the known allergen triggers were not a listed ingredient. METHODS: A
      questionnaire was sent to all members of the Australasian Society of Clinical
      Immunology and Allergy (n = 548). Participants were asked to complete a survey
      reporting whether they have had seen any patients over the last 3 months
      reporting anaphylaxis following ingestion of a packaged food where the suspected
      food allergen was not a listed ingredient. RESULTS: Of the n = 548 members
      approached, n = 198 responded (response rate 36.1%).There were 14 reports of
      anaphylaxis to packaged foods (where the suspected allergen was not a listed
      ingredient), which met the case definition from a total of 198 respondents over
      the 9-month period. Of those reactions, 50.0% (confidence interval 95% 21-78)
      were reported from foods that did not have a PAL statement, and 50.0% (confidence
      interval 95% 21-78) were due to peanuts. CONCLUSION: Anaphylaxis to undeclared
      allergens was not rare and did not appear to depend on whether the product was
      labelled with precautionary advice. There is currently no reliable labelling
      system that can inform food-allergic consumers of safer food choices.
      Improvements in the regulation of food labelling with PAL are required.

PMID- 29363216
TI  - Diagnostic yield of a targeted gene panel in primary ciliary dyskinesia patients.
AB  - We aimed to determine the diagnostic yield of a targeted-exome panel in a cohort
      of 74 Dutch primary ciliary dyskinesia (PCD) patients. The panel consisted of 26
      PCD-related and 284 candidate genes. To prioritize PCD candidate genes, we
      investigated the transcriptome of human airway cells of 12 healthy volunteers
      during in vitro ciliogenesis and hypothesized that PCD-related genes show
      significant upregulation. We compared gene expression in epithelial precursor
      cells grown as collagen monolayer and ciliated cells grown in suspension by RNA
      sequencing. All genes reported as PCD causative, except NME8, showed significant
      upregulation during in vitro ciliogenesis. We observed 67.6% diagnostic yield
      when testing the targeted-exome panel in our cohort. There was relatively high
      percentage of DNAI and HYDIN mutations compared to other countries. The latter
      may be due to our solution for the problem of the confounding HYDIN2 pseudogene.
      Candidate genes included two recently published PCD-related genes DNAJB13 and
      PIH1D3; identification of the latter was a direct result of this study. In
      conclusion, we demonstrate 67.6% diagnostic yield by targeted exome sequencing in
      a Dutch PCD population and present a highly sensitive and moderately specific
      approach for identification of PCD-related genes, based on significant
      upregulation during in vitro ciliogenesis.

PMID- 29363217
TI  - Predicting drug efficacy in chronic low back pain by quantitative sensory tests.
AB  - BACKGROUND: Drugs are prescribed for chronic low back pain without knowing in
      advance whether a patient will respond to them or not. Quantitative sensory tests
      (QST) can discriminate patients according to sensory phenotype, possibly
      reflecting underlying mechanisms of pain processing. QST may therefore be a
      screening tool to identify potential responders to a certain drug. The aim of
      this study was to investigate whether QST can predict analgesic effects of
      oxycodone, imipramine and clobazam in chronic low back pain. METHODS: Oxycodone
      15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were
      compared to active placebo tolterodine 1 mg in a randomized, double-blinded,
      crossover fashion. Electrical, pressure and thermal QST were performed at
      baseline and after 1 and 2 h. Pain intensity was assessed on a 0-10 numeric
      rating scale every 30 min for up to 2 h. The ability of baseline QST to predict
      pain reduction after 2 h was analysed using linear mixed models. Genetic variants
      of drug-metabolizing enzymes and genes affecting pain sensitivity were examined
      as covariables. RESULTS: No predictor of analgesic effect was found for oxycodone
      and clobazam. Thermal QST was associated with analgesic effect of imipramine:
      patients more sensitive to heat or cold were more likely to experience an effect
      of imipramine. Pharmacogenetic variants and pain-related candidate genes were not
      associated with drug efficacy. CONCLUSIONS: Thermal QST have the potential to
      predict imipramine effect in chronic low back pain. Oxycodone and clobazam
      effects could not be predicted by any of the selected QST or genetic variants.
      SIGNIFICANCE: Predicting drug efficacy in chronic low back pain remains
      difficult. There is some evidence that patients more sensitive to heat and cold
      pain respond better to imipramine.

PMID- 29363218
TI  - Carers' preferences for the delivery of therapy services for people with
      disability in rural Australia: evidence from a discrete choice experiment.
AB  - BACKGROUND: The implementation of the Australian National Disability Insurance
      Scheme is expected to generate a responsive, person-centred system that will
      empower people with disability to choose the services and support they receive.
      However, little attention has been paid to examine how users of the National
      Disability Insurance Scheme will choose and spend their individual budgets. This
      study aimed to determine quantitatively the relative importance that carers of
      people with a disability living in rural Australia place on different therapy
      service delivery characteristics. METHODS: A stated preference discrete choice
      experiment was incorporated into a survey of carers of people with disability
      living in rural Australia. Carers chose between therapy delivery services
      differing in attributes such as travel time to receive therapy, sector providing
      the service (i.e. Government, not-for-profit and private), out-of-pocket costs,
      person who delivers the therapy (therapist or other staff) and waiting time.
      RESULTS: A total of 133 carers completed the discrete choice experiment. The
      majority of respondents cared for a child with a disability (84%); the average
      age of the person they cared for was 17 years (SD 14.25). Participants expressed
      strong preferences for a short waiting time (0-3 months) to receive therapy
      services; services delivered by a therapist, no out-of-pocket cost and travelling
      up to 4 h to receive a therapy session (P < 0.05). Sector providing the service
      was not statistically significant. CONCLUSION: Carers of people with a disability
      in rural Australia exhibited strongest preferences for short waiting times (0-3
      months). Therapy services that are delivered by therapy assistants or support
      workers will require careful introduction to achieve uptake and acceptability.

PMID- 29363219
TI  - Microscopic abnormality classification of cardiac murmurs using ANFIS and HMM.
AB  - Auscultation of heart dispenses identification of the cardiac valves. An
      electronic stethoscope is used for the acquisition of heart murmurs that is
      further classified into normal or abnormal murmurs. The process of heart sound
      segmentation involves discrete wavelet transform to obtain individual components
      of the heart signal and its separation into systole and diastole intervals. This
      research presents a novel scheme to develop a semi-automatic cardiac valve
      disorder diagnosis system. Accordingly, features are extracted using wavelet
      transform and spectral analysis of input signals. The proposed classification
      scheme is the fusion of adaptive-neuro fuzzy inference system (ANFIS) and HMM.
      Both classifiers are trained using the extracted features to correctly identify
      normal and abnormal heart murmurs. Experimental results thus achieved exhibit
      that proposed system furnishes promising classification accuracy with excellent
      specificity and sensitivity. However, the proposed system has fewer
      classification errors, fewer computations, and lower dimensional feature set to
      build an intelligent system for detection and classification of heart murmurs.

PMID- 29363221
TI  - Pretreatment with magnesium sulfate attenuates white matter damage by preventing
      cell death of developing oligodendrocytes.
AB  - AIM: Antenatal maternal administration of magnesium sulfate (MgSO4 ) reduces
      cerebral palsy in preterm infants. However, it remains controversial as to
      whether it also reduces occurrence of white matter damage, or periventricular
      leukomalacia. We assessed the effect of MgSO4 against white matter damage induced
      by hypoxic-ischemic insult using a neonatal rat model and culture of
      premyelinating oligodendrocytes (pre-OL). METHODS: Rat pups at postnatal day (P)
      6 were administered either MgSO4 or vehicle intraperitoneally before hypoxic
      ischemic insult (unilateral ligation of the carotid artery followed by 6% oxygen
      for 1 h). The population of oligodendrocyte (OL) markers and CD-68-positive
      microglia at P11, and TdT-mediated biotin-16-dUTP nick-end labeling (TUNEL)
      positive cells at P8 were evaluated in pericallosal white matter. Primary
      cultures of mouse pre-OL were subjected to oxygen glucose deprivation condition,
      and the lactate dehydrogenase release from culture cells was evaluated to assess
      cell viability. RESULTS: Pretreatment with MgSO4 attenuated the loss of OL
      markers, such as myelin basic protein and Olig2, in ipsilateral pericallosal
      white matter and decreased the number of CD-68-positive microglia and TUNEL
      positive cells in vivo. Pretreatment with MgSO4 also inhibited lactate
      dehydrogenase release from pre-OL induced by oxygen glucose deprivation in vitro.
      CONCLUSION: Pretreatment with MgSO4 attenuates white matter damage by preventing
      cell death of pre-OL.

PMID- 29363220
TI  - Applying genomics in heart transplantation.
AB  - While advances in patient care and immunosuppressive pharmacotherapies have
      increased the lifespan of heart allograft recipients, there are still significant
      comorbidities post-transplantation and 5-year survival rates are still
      significant, at approximately 70%. The last decade has seen massive strides in
      genomics and other omics fields, including transcriptomics, with many of these
      advances now starting to impact heart transplant clinical care. This review
      summarizes a number of the key advances in genomics which are relevant for heart
      transplant outcomes, and we highlight the translational potential that such
      knowledge may bring to patient care within the next decade.

PMID- 29363222
TI  - Obliterative portal venopathy: A histopathologic finding associated with chronic
      antibody-mediated rejection in pediatric liver allografts.
AB  - The significance of post-transplant HLA DSA and chronic AMR in LT is an emerging
      field of study. Although OPV has previously been described as a histopathologic
      finding in DSA-positive adult LT recipients, it was not included in the recent
      Banff criteria for chronic AMR. Our aim was to describe the association between
      OPV and chronic AMR in pediatric LT recipients. A retrospective review of 67
      liver biopsies performed between November 2014 and April 2016 in 45 pediatric LT
      recipients identified four patients with OPV. Clinical status, liver
      biochemistry, the presence of DSA, and available non-HLA antibody testing, as
      well as histopathologic features of chronic AMR, were assessed. All four patients
      with OPV had class II DSA and histopathologic features of chronic AMR based on
      the Banff criteria. Two patients were noted to have non-HLA antibodies. Three
      patients are undergoing treatment with IVIG but have persistent DSA. Two patients
      have graft failure and are awaiting retransplantation. In conclusion, OPV is a
      histopathologic finding associated with chronic AMR in pediatric LT recipients.
      Further studies are needed to elucidate whether OPV is reversible and/or amenable
      to medical therapy.

PMID- 29363223
TI  - The allometric scaling of body mass and height in children and adolescents in
      five countries.
AB  - OBJECTIVE: The purpose a methodology that excludes values outside of the expected
      spectrum for age (VOESA) of height and body mass in the definition of power (p)
      to construct an international allometric body mass index (AI) for children and
      adolescents. METHODS: Datasets of national surveys including individuals (aged 0
      19 years) from five countries (Brazil, South Korea, Mexico, England, and the USA)
      were selected. The p was defined for each country, age range, and sex after
      exclusion of VOESA for height and weight by log-log linear regression, where beta
      represented p. The p was also defined for a pool of five countries, international
      p (ip) after exclusion of VOESA using a spline modeling technique (5 knots). The
      AI was calculated and Pearson's correlation coefficient (r) was calculated to
      investigate the correlation between AI and height. RESULTS: Exclusion of VOESA
      decreased the difference of p among countries. Exponent p showed values close to
      2 in the first years of life, increased to 3-3.5 between 7 and 11 years for girls
      and 8 to 12 years for boys, and decreased to close to 2 near the end of growth
      (16 years for girls and 19 years for boys). The use of ip for all countries
      decreased r values to near zero while BMI had values near 0.4. CONCLUSIONS:
      Exclusion of VOESA contributes to a decreased effect of epidemiological context
      among countries when calculating the AI. AI calculated using ip is independent of
      height in all countries and reflects physiological growth changes for children
      and adolescents.

PMID- 29363224
TI  - NKX6.1 hypermethylation predicts the outcome of stage II colorectal cancer
      patients undergoing chemotherapy.
AB  - Colorectal cancer (CRC) is a common malignancy worldwide. CRC patients in the
      same stage often present with dramatically different clinical scenarios. Thus,
      robust prognostic biomarkers are urgently needed to guide therapies and improve
      treatment outcomes. The NKX6.1 gene has been identified as a hypermethylation
      marker in cervical cancer, functioning as a metastasis suppressor by regulating
      epithelial-mesenchymal transition. Here, we investigated whether hypermethylation
      of NKX6.1 might be a prognostic biomarker for CRC. By analyzing the methylation
      and expression of NKX6.1 in CRC tissues and CRC cell lines. We quantitatively
      examined the NKX6.1 methylation levels in 151 pairs of CRC tissues by using
      methylation-specific polymerase chain reaction analysis and found that NKX6.1 was
      hypermethylated in 35 of 151 CRC tissues (23%). NKX6.1 gene expression was
      inversely correlated with the DNA methylation level in CRC cell lines in vitro.
      Then, we analyzed the association of NKX6.1 methylation with clinical
      characteristics of these CRC patients. Our data demonstrated that patients with
      NKX6.1 methylation presented poorer 5-year overall survival (P = 0.0167) and
      disease-free survival (P = 0.0083) than patients without NKX6.1 methylation after
      receiving adjuvant chemotherapy. Most importantly, these data revealed that stage
      II CRC patients with NKX6.1 methylation had poorer 5-year disease-free survival
      (P = 0.0322) than patients without NKX6.1 methylation after adjuvant
      chemotherapy. Our results demonstrate that methylation of NKX6.1 is a novel
      prognostic biomarker in CRC and that it may be used as a predictor of the
      response to chemotherapy.

PMID- 29363225
TI  - Uptake of adjuvant breast cancer treatments recommended by multi-disciplinary
      meetings.
AB  - BACKGROUND: Adjuvant therapy for breast cancer is routinely discussed and
      recommended in multi-disciplinary meetings (MDMs). Current literature explores
      how treatments received by patients differ from national guidelines; however, it
      does not explore whether treatment is concordant with MDMs. This study provides
      an Australian perspective on the uptake of MDM recommendations and reasons for
      non-concordance. METHODS: A retrospective cohort study of patients with breast
      cancer presented at The Royal Melbourne Hospital MDM in 2010 and 2014 to
      investigate the concordance between MDM recommendations and treatment received.
      RESULTS: The study group comprised 441 patients (161 from 2010 and 280 from
      2014). A total of 375 patients were included in the analyses. Overall, 82% of
      patients had perfect concordance between recommended and received treatment for
      all modes of adjuvant therapy. Concordance to endocrine therapy was higher for
      invasive cancers than ductal carcinoma in situ (97% versus 81%, P < 0.0001).
      Concordance to radiotherapy was high and did not differ according to type of
      cancer or surgery (ranging from 88 to 91%). Concordance to chemotherapy
      recommendations was high overall (92%) and did not vary with nodal status. Women
      aged over 65 years were least likely to be recommended for adjuvant therapy but
      most likely to concordant with the recommendation. CONCLUSIONS: Uptake of MDM
      recommended treatments is high. There is a minority of patients in whom MDM
      recommendations are not followed, highlighting that there are extra steps between
      recommendations at an MDM and decisions with patients. More attention to this
      issue is appropriate, and the reasons for non-concordance warrant further study.

PMID- 29363226
TI  - Magnetoencephalographic study of event-related fields and cortical oscillatory
      changes during cutaneous warmth processing.
AB  - Thermoreception is an important cutaneous sense, which plays a role in the
      maintenance of our body temperature and in the detection of potential noxious
      heat stimulation. In this study, we investigated event-related fields (ERFs) and
      neural oscillatory activities, which were modulated by warmth stimulation. We
      developed a warmth stimulator that could elicit a warmth sensation, without pain
      or tactile sensation, by using a deep-penetrating 980-nm diode laser. The index
      finger of each participant (n = 24) was irradiated with the laser warmth
      stimulus, and the cortical responses were measured using magnetoencephalography
      (MEG). The ERFs and oscillatory responses had late latencies (~1.3 s and 1.0-1.5
      s for ERFs and oscillatory responses, respectively), which could be explained by
      a slow conduction velocity of warmth-specific C-fibers. Cortical sources of
      warmth-related ERFs were seen in the bilateral primary and secondary
      somatosensory cortices (SI and SII), posterior part of the anterior cingulate
      cortex (pACC), ipsilateral primary motor, and premotor cortex. Thus, we suggested
      that SI, SII, and pACC play a role in processing the warmth sensation. Time
      frequency analysis demonstrated the suppression of the alpha (8-13 Hz) and beta
      (18-23 Hz) band power in the bilateral sensorimotor cortex. We proposed that the
      suppressions in alpha and beta band power are involved in the automatic response
      to the input of warmth stimulation and sensorimotor interactions. The delta band
      power (1-4 Hz) increased in the frontal, temporal, and cingulate cortices. The
      power changes in delta band might be related with the attentional processes
      during the warmth stimulation.

PMID- 29363228
TI  - Discrepancy of width between actual cutaneous lesion and punch biopsy specimen.

PMID- 29363227
TI  - Expression of activating natural killer-cell receptors is a hallmark of the
      innate-like T-cell neoplasm in peripheral T-cell lymphomas.
AB  - Peripheral T- or natural killer (NK)-cell lymphomas are rare and difficult-to
      recognize diseases. It remains arduous to distinguish between NK cell- and
      cytotoxic T-lymphocyte-derived lymphomas through routine histological evaluation.
      To clarify the cells of origin, we focused on NK-cell receptors and examined the
      expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms
      comprising angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)
      positive and -negative anaplastic large-cell lymphomas, extranodal NK/T-cell
      lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma,
      aggressive NK-cell leukemia, and other peripheral T-cell lymphomas. Inhibitory
      receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) was
      detected in 14 (64%) cases, whereas activating receptors DNAM1, NKp46, and NKG2D
      were expressed in 7 (32%), 9 (41%), and 5 (23%) cases, respectively. Although
      LILRB1 was detected regardless of the disease entity, the activating NK-cell
      receptors were expressed predominantly in TIA-1-positive neoplasms (DNAM1, 49%;
      NKp46, 69%; and NKG2D, 38%). In addition, NKp46 and NKG2D were detected only in
      NK-cell neoplasms and cytotoxic T-lymphocyte-derived lymphomas including
      monomorphic epitheliotropic intestinal T-cell lymphoma. One Epstein-Barr virus
      harboring cytotoxic T-lymphocyte-derived lymphoma mimicking extranodal NK/T-cell
      lymphoma, nasal type lacked these NK-cell receptors, indicating different cell
      origin from NK and innate-like T cells. Furthermore, NKG2D expression showed a
      negative impact on survival among the 22 examined cases, which mainly received
      the standard chemotherapy regimen (log-rank test, P = .024). We propose that the
      presence of activating NK-cell receptors may provide new insights into
      understanding peripheral T-cell lymphomas and characterizing them as innate-like
      T-cell neoplasm.

PMID- 29363229
TI  - Acupuncture inhibition of methamphetamine-induced behaviors, dopamine release and
      hyperthermia in the nucleus accumbens: mediation of group II mGluR.
AB  - Methamphetamine (METH) increases metabolic neuronal activity in the mesolimbic
      dopamine (DA) system and mediates the reinforcing effect. To explore the
      underlying mechanism of acupuncture intervention in reducing METH-induced
      behaviors, we investigated the effect of acupuncture on locomotor activity,
      ultrasonic vocalizations, extracellular DA release in the nucleus accumbens
      (NAcs) using fast-scan cyclic voltammetry and alterations of brain temperature
      (an indicator of local brain metabolic activity) produced by METH administration.
      When acupuncture was applied to HT7, but not TE4, both locomotor activity and 50
      kHz ultrasonic vocalizations were suppressed in METH-treated rats. Acupuncture at
      HT7 attenuated the enhancement of electrically stimulated DA release in the NAc
      of METH-treated rats. Systemic injection of METH produced a sustained increase in
      NAc temperature, which was reversed by the DA D1 receptor antagonist SCH 23390 or
      acupuncture at HT7. Acupuncture inhibition of METH-induced NAc temperature was
      prevented by pre-treatment with a group II metabotropic glutamate receptors
      (mGluR2/3) antagonist EGLU into the NAc or mimicked by injection of an mGluR2/3
      agonist DCG-IV into the NAc. These results suggest that acupuncture reduces
      extracellular DA release and metabolic neuronal activity in the NAc through
      activation of mGluR2/3 and suppresses METH-induced affective states and locomotor
      behavior.

PMID- 29363230
TI  - Self-management for bipolar disorder and the construction of the ethical self.
AB  - The promotion of the self-managing capacities of people has become a marker of
      contemporary mental health practice, yet self-management remains a largely
      uncontested construct in mental health settings. This discourse analysis based
      upon the work of Foucault investigates self-management practices for bipolar
      disorder and their action upon how a person with bipolar disorder comes to think
      of who they are and how they should live. Using Foucault's framework for
      exploring the ethical self and transcripts of interviews with people living with
      bipolar disorder, this discourse analysis finds that the discursive practices of
      self-management for bipolar disorder are prescribing a restricted regime for
      living based upon the quintessential neo-liberal subject using practices that are
      focused upon managing an unreliable and problematic self. The article concludes
      with the proposition that the problem of bipolar disorder (for which self
      management is an answer) is less about the object itself and more about how we
      construct the nature of the self. A Maori indigenous ontology is used here as an
      example of an alternative discursive resource through which people make sense of
      the self and which allows ways of thinking about self-management that engage with
      ambivalence and ambiguity rather than restriction and regulation.

PMID- 29363231
TI  - Wiring taste receptor cells to the central gustatory system.
AB  - Taste receptor cells in the tongue are epithelial in nature and turnover
      frequently. Taste receptor cell-associated neurons carrying bitter, sweet, or
      sour signals never turnover and are hardwired to specific gustatory centers in
      the brain. How can ever-changing bitter or sweet receptors find never-changing
      neurons that must match the specificity of the signal? This article reviews a
      recent paper published in Nature (Lee, MacPherson, Parada, Zuker, & Ryba, ,
      548:330-333) that identified two molecules belonging to the semaphorin axon
      guidance family of molecules (SEMA3A and SEMA7A) that help maintain the "labeled
      line principle" between peripheral bitter or sweet receptors and their respective
      central projection area in the gustatory center.

PMID- 29363232
TI  - Relevant obstetric factors associated with fetal heart rate monitoring for
      cerebral palsy in pregnant women with hypertensive disorder of pregnancy.
AB  - AIM: The study identifies the relevant obstetric factors associated with fetal
      heart rate (FHR) monitoring for cerebral palsy (CP) in pregnant women with
      hypertensive disorders of pregnancy (HDP). METHODS: The subjects were neonates
      with CP (birth weight >= 2000 g, gestational age >= 33 weeks) who were approved
      for compensation for CP by the Operating Organization of the Japan Obstetric
      Compensation System between 2009 and 2012. After selection of women with
      antepartum HDP, obstetric characteristics associated with FHR monitoring were
      analyzed. RESULTS: The subjects included 33 neonates with CP whose mothers
      suffered from HDP during pregnancy and 450 neonates whose mothers did not develop
      HDP. The rates of placental abruption (48.5% vs. 20%; P < 0.001) and light-for
      gestational age (12.1% vs. 2.2%; P = 0.011) were significantly higher in women
      with HDP than in those without HDP. Regarding FHR pattern analysis, fetal
      bradycardia was observed on admission to hospital in 94% of women with placental
      abruption. In women without placental abruption, FHR was likely to indicate a
      favorable pattern on admission, but became worse with the progression of labor.
      CONCLUSION: This is first study to clinically demonstrate FHR patterns in CP
      cases in association with HDP. Although antepartum CP is undetectable, pregnant
      women with HDP should be placed under strict observation and management to
      minimize fetal hypoxic conditions during labor.

PMID- 29363233
TI  - Serum microRNA signatures and metabolomics have high diagnostic value in
      colorectal cancer using two novel methods.
AB  - Recently, many new diagnostic biomarkers have been developed for colorectal
      cancer. We chose 2 methods with high diagnostic efficiency, the detection of
      serum microRNA and metabolomics based on gas chromatography/mass spectrometry
      (GC/MS), and aimed to establish appropriate models. We reviewed the diagnostic
      value of all microRNA identified by previous diagnostic tests. We selected
      appropriate microRNA to validate their diagnostic efficiency, and determined the
      optimal combination. We included 85 patients with colorectal cancer (CRC) and 78
      healthy controls (HC) and detected the expression of the microRNA. GC/MS analysis
      was conducted, and we used 3 multivariate statistical methods to establish
      diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and
      carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel
      models. Ultimately, 62 published studies and 63 microRNA were included in this
      review. MiR-21, miR-29a, miR-92a, miR-125b and miR-223 were selected to further
      validate their diagnostic value. The serum levels of the 5 microRNA in CRC
      patients were significantly higher than those in the HC. The combination of miR
      21, miR-29a, miR-92a and miR-125b had the highest area under the curve (AUC) at
      0.952, with a sensitivity of 84.7% and a specificity of 98.7%. The GC/MS analysis
      exhibited an excellent diagnostic value and the AUC reached 1.0. With regard to
      traditional biomarkers, the AUC of CEA and CA19-9 were 0.808 and 0.705,
      respectively. The application prospects are good for microRNA and metabolomics as
      new diagnostic methods because of their high diagnostic value compared with
      traditional biomarkers.

PMID- 29363234
TI  - Stepwise Hydride Transfer in a Biological System: Insights into the Reaction
      Mechanism of the Light-Dependent Protochlorophyllide Oxidoreductase.
AB  - Hydride transfer plays a crucial role in a wide range of biological systems.
      However, its mode of action (concerted or stepwise) is still under debate. Light
      dependent NADPH: protochlorophyllide oxidoreductase (POR) catalyzes the
      stereospecific trans addition of a hydride anion and a proton across the C17 -C18
      double bond of protochlorophyllide. Time-resolved absorption and emission
      spectroscopy were used to investigate the hydride transfer mechanism in POR.
      Apart from excited states of protochlorophyllide, three discrete intermediates
      were resolved, consistent with a stepwise mechanism that involves an initial
      electron transfer from NADPH. A subsequent proton-coupled electron transfer
      followed by a proton transfer yield distinct different intermediates for wild
      type and the C226S variant, that is, initial hydride attaches to either C17 or
      C18 , but ends in the same chlorophyllide stereoisomer. This work provides the
      first evidence of a stepwise hydride transfer in a biological system.

PMID- 29363236
TI  - The [U2 F12 ]2- Anion of Sr[U2 F12 ].
AB  - The D2h -symmetric dinuclear complex anion [U2 F12 ]2- of pastel green Sr[U2 F12
      ] shows a hitherto unknown structural feature: The coordination polyhedra around
      the U atoms are edge-linked monocapped trigonal prisms, the UV atoms are
      therefore seven-coordinated. This leads to a U-U distance of 3.8913(6) A. A weak
      UV -UV interaction is observed for the dinuclear [U2 F12 ]2- complex and
      described by the antiferromagnetic exchange Jexp of circa -29.9 cm-1 . The
      crystalline compound can be easily prepared from SrF2 and beta-UF5 in anhydrous
      hydrogen fluoride (aHF) at room temperature. It was studied by means of single
      crystal X-ray diffraction, IR, Raman and UV/VIS spectroscopy, magnetic
      measurements, and by molecular as well as by solid-state quantum chemical
      calculations.

PMID- 29363237
TI  - Liver resection for hepatocellular carcinoma: personal experiences in a series of
      1330 consecutive cases in China.
AB  - BACKGROUND: Liver resection to treat early stage hepatocellular carcinoma (HCC)
      is widely practised but surgery for intermediate and advanced stages of HCC is
      not included in the treatment algorithm of the Barcelona Clinic Liver Cancer,
      which has been adopted in official guidelines; nevertheless, resection beyond
      early stages is frequently undertaken and documented. METHODS: Between January
      2001 and December 2014, all the HCC patients who underwent liver resection for
      the first time by Dr Yiqun Yan and his surgical team were enrolled. Clinical data
      were prospectively collected as well as the follow-up results. RESULTS: A total
      of 1330 consecutive patients were included in the study, of which 452 (34.0%)
      suffered complications after liver resection with a mortality of 0.7%. The
      overall survival rates at 1-, 3- and 5-year were 91.2, 63.3 and 36.9%,
      respectively, while the disease-free survival rates at 1-, 3- and 5-year were
      67.7, 33.7 and 13.8%, respectively. Cases were classified into Barcelona Clinic
      Liver Cancer stage A (548 patients, 41.2%), stage B (613 patients, 46.1%) and
      stage C (169 patients, 12.7%). The overall survival time at 5-year were 49.8,
      32.8 and 10.6%, respectively, in patients with stage A, B and C tumours.
      CONCLUSION: Liver resection to treat HCC is safe in patients with preserved liver
      function and good functional status. Liver resection should be the first line
      therapy in patients with single (regardless of tumour size) and resectable 2-3
      tumours as well as vascular tumour thrombus if the tumour thrombus does not
      invade the major trunks.

PMID- 29363235
TI  - E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T
      cell lymphoma: A phase I study.
AB  - E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin
      fragments A and B and human interleukin-2, shares an amino acid sequence with
      denileukin diftitox but has improved purity and an increased percentage of active
      protein monomer species. A phase I study was carried out to evaluate the
      tolerability, safety, pharmacokinetics, and antitumor activity of E7777 in
      Japanese patients with relapsed/refractory peripheral and cutaneous T-cell
      lymphoma. E7777 (6, 12, and expanded 9 MUg/kg/day) was given to 13 patients by
      i.v. infusion on five consecutive days per 21-day cycle. Dose-limiting
      toxicities, including increased alanine aminotransferase, hyponatremia (n = 2),
      hypokalemia, lymphopenia, fatigue, hypoalbuminemia, rash, and increased lipase (n
      = 1), were observed in all three patients in the 12 MUg/kg/day cohort, whereas
      two of six patients in the 9 MUg/kg/day cohort showed decreased appetite or
      fatigue. The maximum tolerated and recommended dose of E7777 was 9 MUg/kg/day for
      five consecutive days per 21-day cycle. The objective response rate was 38%
      (5/13) and did not appear to depend on tumor expression of CD25. E7777 was well
      tolerated, assuming careful management of adverse events during treatment, and
      preliminary but clinically meaningful antitumor activity was observed. Subsequent
      studies of E7777 for T-cell lymphomas are warranted. This study was registered
      with www.ClinicalTrials.gov (NCT1401530).

PMID- 29363238
TI  - Direct Room-Temperature Conversion of Methane into Protonated Formaldehyde: The
      Gas-Phase Chemistry of Mercury among the Zinc Triad Oxide Cations.
AB  - In thermal reactions of methane with diatomic metal oxides [MO].+ of the zinc
      triad (M=Zn, Cd, Hg), protonated formaldehyde [CH2 OH]+ is generated as the major
      product only for the [HgO].+ /CH4 couple. Mechanistic insight is provided by high
      level quantum-chemical calculations, and relativistic effects are suggested to be
      the root cause for the unexpected thermal production of [CH2 OH]+ from [HgO].+
      /CH4 .

PMID- 29363239
TI  - Nucleophile Promiscuity of Engineered Class II Pyruvate Aldolase YfaU from E.
      Coli.
AB  - Pyruvate-dependent aldolases exhibit a stringent selectivity for pyruvate,
      limiting application of their synthetic potential, which is a drawback shared
      with other existing aldolases. Structure-guided rational protein engineering
      rendered a 2-keto-3-deoxy-l-rhamnonate aldolase variant, fused with a maltose
      binding protein (MBP-YfaU W23V/L216A), capable of efficiently converting larger
      pyruvate analogues, for example, those with linear and branched aliphatic chains,
      in aldol addition reactions. Combination of these nucleophiles with N-Cbz
      alaninal (Cbz=benzyloxycarbonyl) and N-Cbz-prolinal electrophiles gave access to
      chiral building blocks, for example, derivatives of (2S,3S,4R)-4-amino-3-hydroxy
      2-methylpentanoic acid (68 %, d.r. 90:10) and the enantiomer of dolaproine (33 %,
      d.r. 94:6) as well as a collection of unprecedented alpha-amino acid derivatives
      of the proline and pyrrolizidine type. Conversions varied between 6-93 % and
      diastereomeric ratios from 50:50 to 95:5 depending on the nucleophilic and
      electrophilic components.

PMID- 29363240
TI  - Magnesium attenuates endothelin-1-induced vasoreactivity and enhances
      vasodilatation in mouse pulmonary arteries: Modulation by chronic hypoxic
      pulmonary hypertension.
AB  - NEW FINDINGS: What is the central question of this study? The central goal of
      this study was to elucidate the role of magnesium in the regulation of pulmonary
      vascular reactivity in relationship to hypoxic pulmonary hypertension. What is
      the main finding and its importance? We found that magnesium is essential for
      normal vasoreactivity of the pulmonary artery. Increasing the magnesium
      concentration attenuates vasoconstriction and improves vasodilatation via release
      of nitric oxide. Pulmonary hypertension is associated with endothelial
      dysfunction resulting in the suppression of magnesium modulation of
      vasodilatation. These results provide evidence that magnesium is important for
      the modulation of pulmonary vascular function. ABSTRACT: Pulmonary hypertension
      (PH) is characterized by enhanced vasoreactivity and sustained pulmonary
      vasoconstriction, arising from aberrant Ca2+ homeostasis in pulmonary arterial
      (PA) smooth muscle cells. In addition to Ca2+ , magnesium, the most abundant
      intracellular divalent cation, also plays crucial roles in many cellular
      processes that regulate cardiovascular function. Recent findings suggest that
      magnesium regulates vascular functions by altering the vascular responses to
      vasodilator and vasoactive agonists and affects endothelial function by
      modulating endothelium-dependent vasodilatation in hypertension. Administration
      of magnesium also decreased pulmonary arterial pressure and improved cardiac
      output in animal models of PH. However, the role of magnesium in the regulation
      of pulmonary vascular function related to PH has not been studied. In this study,
      we examined the effects of magnesium on endothelin-1 (ET-1)-induced
      vasoconstriction, ACh-induced vasodilatation and the generation of NO in PAs of
      normoxic mice and chronic hypoxia (CH)-treated mice. Our data showed that removal
      of extracellular magnesium suppressed vasoreactivity of PAs to both ET-1 and ACh.
      A high concentration of magnesium (4.8 mm) inhibited ET-1-induced
      vasoconstriction in endothelium-intact or endothelium-disrupted PAs of normoxic
      and CH-treated mice, and enhanced the ACh-induced production of NO in PAs of
      normoxic mice. Moreover, magnesium enhanced ACh-induced vasodilatation in PAs of
      normoxic mice, and the enhancement was completely abolished after exposure to CH.
      Hence, in this study we demonstrated that increasing the magnesium concentration
      can attenuate the ET-1-induced contractile response and improve vasodilatation
      via release of NO from the endothelium. We also demonstrated that chronic
      exposure to hypoxia can cause endothelial dysfunction resulting in suppression of
      the magnesium-dependent modulation of vasodilatation.

PMID- 29363241
TI  - Porphyrin-Based Symmetric Redox-Flow Batteries towards Cold-Climate Energy
      Storage.
AB  - Electrochemical energy storage with redox-flow batteries (RFBs) under subzero
      temperature is of great significance for the use of renewable energy in cold
      regions. However, RFBs are generally used above 10  degrees C. Herein we present
      non-aqueous organic RFBs based on 5,10,15,20-tetraphenylporphyrin (H2 TPP) as a
      bipolar redox-active material (anode: [H2 TPP]2- /H2 TPP, cathode: H2 TPP/[H2
      TPP]2+ ) and a Y-zeolite-poly(vinylidene fluoride) (Y-PVDF) ion-selective
      membrane with high ionic conductivity as a separator. The constructed RFBs
      exhibit a high volumetric capacity of 8.72 Ah L-1 with a high voltage of 2.83 V
      and excellent cycling stability (capacity retention exceeding 99.98 % per cycle)
      in the temperature range between 20 and -40  degrees C. Our study highlights
      principles for the design of RFBs that operate at low temperatures, thus offering
      a promising approach to electrochemical energy storage under cold-climate
      conditions.

PMID- 29363243
TI  - A cohort study assessing the impact of small volume blood tubes on diagnostic
      test quality and iatrogenic blood loss in a cohort of adult haematology patients.
AB  - BACKGROUND/AIM: To estimate the reduction in blood volume loss and impact on
      diagnostic test quality associated with introduction of small volume blood tubes
      in a cohort of haematology inpatients compared to a historical comparator group.
      METHODS: Prospective cohort study of haematology inpatients admitted to a
      tertiary referral hospital in Adelaide. Small volume blood tubes were used in an
      intervention cohort admitted between 2012 and 2013 and compared to a control
      cohort admitted between 2009 and 2010 where standard volume blood tubes had been
      used. The diagnostic test quality, specimen integrity and total reduction in
      blood loss associated with small volume blood tubes were estimated. RESULTS:
      Small volume blood tubes demonstrated acceptable collinearity on commonly assayed
      haematological and biochemical parameters. Small volume tubes were associated
      with a 42% reduction in blood volume loss equating to a saving of 8.5 mL per
      patient per day or 180 mL of blood loss over a 3-week admission. Small volume
      blood tubes were associated with a slight but significantly increased rate of
      fibrin contamination of ethylenediaminetetraacetic acid samples (0.2-0.5% of
      specimens). CONCLUSION: Small volume blood tubes are associated with a
      substantial reduction in total blood volume collected per day in haematology
      inpatients. They have similar diagnostic validity and sample integrity to that of
      standard volume containers.

PMID- 29363242
TI  - The outcome of patients with severe and severe-complicated Clostridium difficile
      infection treated with tigecycline combination therapy: a retrospective
      observational study.
AB  - BACKGROUND: Tigecycline is a third-line therapy for severe Clostridium difficile
      infection (CDI) in Australasian guidelines. Differences in strain types make it
      difficult to extrapolate international tigecycline efficacy data with combination
      or monotherapy to Australian practice, where experience is limited. AIM: To
      evaluate the efficacy and adverse effects associated with tigecycline combination
      therapy for severe and severe-complicated CDI in an Australian healthcare
      setting. METHODS: This was a retrospective observational study at a metropolitan
      university-affiliated hospital. All patients between February 2013 and October
      2016 treated with adjunctive intravenous tigecycline for >48 h for severe or
      severe-complicated CDI were included. Tigecycline was given in addition to oral
      vancomycin +/- intravenous metronidazole. The primary outcome was all-cause
      mortality at 30 days from start of tigecycline combination therapy. Secondary
      outcomes included clinical cure, colectomy, adverse events and recurrence rates.
      RESULTS: Thirteen patients with median age of 61 years had severe (n = 9) or
      severe-complicated (n = 4) CDI at tigecycline commencement. In 92% of patients,
      tigecycline started within 48 h after in-hospital CDI treatment, for median
      duration of 9 days. All-cause mortality at 30 days was 8% with no mortality in
      severe CDI and 25% (1/4) in patients with severe-complicated fulminant CDI,
      comparing favourably with historical rates of 9-38% and 30-80% in similar
      respective groups. Clinical cure was achieved in 77% of cases. There were no
      colectomies and one attributable tigecycline adverse reaction. CONCLUSIONS:
      Tigecycline appears safe and effective as a part of combination therapy in severe
      CDI, and may be given earlier and for shorter durations than in current
      guidelines.

PMID- 29363244
TI  - Stimuli-Responsive Dual-Color Photon Upconversion: A Singlet-to-Triplet
      Absorption Sensitizer in a Soft Luminescent Cyclophane.
AB  - Reversible emission color switching of triplet-triplet annihilation-based photon
      upconversion (TTA-UC) is achieved by employing an Os complex sensitizer with
      singlet-to-triplet (S-T) absorption and an asymmetric luminescent cyclophane with
      switchable emission characteristics. The cyclophane contains the 9,10
      bis(phenylethynyl)anthracene unit as an emitter and can assemble into two
      different structures, a stable crystalline phase and a metastable supercooled
      nematic phase. The two structures exhibit green and yellow fluorescence,
      respectively, and can be accessed by distinct heating/cooling sequences. The
      hybridization of the cyclophane with the Os complex allows near-infrared-to
      visible TTA-UC. The large anti-Stokes shift is possible by the direct S-T
      excitation, which dispenses with the use of a conventional sequence of singlet
      singlet absorption and intersystem crossing. The TTA-UC emission color is
      successfully switched between green and yellow by thermal stimulation.

PMID- 29363245
TI  - The use of natural ingredients in innovative Korean cosmeceuticals.
AB  - BACKGROUND: The cosmeceutical industry is an ever-growing and in demand market,
      especially in Asia. Korea has been on the forefront of creating the newest
      generation and most innovative cosmeceuticals products including ingredients such
      as snail secretions, starfish powder, botanical extracts, green tea, and red
      ginseng. Given their increasing prevalence in the cosmeceutical industry,
      scientists have been conducting investigations into these extracts and their
      properties. OBJECTIVE: To summarize the current literature surrounding multiple
      natural ingredients found in Korean cosmeceutical products. METHODS: A review of
      the literature surrounding natural ingredients found in Korean cosmeceuticals was
      conducted using PubMed (U.S. National Library of Medicine). RESULTS: Multiple
      natural extracts have been found to have antiaging, antitumor, and
      antimelanogenic effects making them useful additives in current cosmeceutical
      products. CONCLUSION: With the public's increasing awareness of cosmeceutical
      products, it is important for physicians to understand the properties of these
      extracts in order to inform patients correctly and ensure patient safety.

PMID- 29363246
TI  - Full-thickness neorectal prolapse after transanal transabdominal
      proctosigmoidectomy for low rectal cancer: a cohort study.
AB  - AIM: Transanal transabdominal proctosigmoidectomy (TATA) with a coloanal
      anastomosis is an alternative to abdominoperineal excision of the rectum (APR)
      for low rectal cancer. Neorectal prolapse is an unusual complication following
      TATA. This study aimed to determine the incidence of neorectal prolapse after
      TATA for low rectal cancer. METHOD: This cohort study was conducted in a tertiary
      referral colorectal centre. From a prospectively maintained database including
      1093 patients treated for rectal cancer between 1984 and 2016 we identified those
      who underwent sphincter-preserving surgery. Data regarding the incidence,
      management and outcomes of neorectal prolapse were analysed. RESULTS: A total of
      409 patients were identified, of whom 185 underwent open surgery and 224 a
      minimally invasive surgical procedure (MIS). All received neoadjuvant
      chemoradiation. Neorectal prolapse occurred in 4.6% (n = 19) with an incidence of
      2.2% in the open and 6.7% in the MIS group (P = 0.023), with no difference
      between MIS techniques. There was one recurrence of neorectal prolapse (5.9%).
      The incidence of neorectal prolapse was higher in women (9.5%) than men (2.5%) (P
      = 0.011). There were no differences in local recurrence rates between the
      neorectal prolapse group (5.3%) and our population without prolapse (3.4%) (P =
      0.79). CONCLUSION: Neorectal prolapse is a rare occurrence following minimally
      invasive sphincter-saving surgical procedures performed for rectal cancer. It
      appears to be more frequent in patients who undergo MIS procedures and in women.

PMID- 29363247
TI  - A Comparative Analysis of the CO-Reducing Activities of MoFe Proteins Containing
      Mo- and V-Nitrogenase Cofactors.
AB  - The Mo and V nitrogenases are structurally homologous yet catalytically distinct
      in their abilities to reduce CO to hydrocarbons. Here we report a comparative
      analysis of the CO-reducing activities of the Mo- and V-nitrogenase cofactors
      (i.e., the M and V clusters) upon insertion of the respective cofactor into the
      same, cofactor-deficient MoFe protein scaffold. Our data reveal a combined
      contribution from the protein environment and cofactor properties to the
      reactivity of nitrogenase toward CO, thus laying a foundation for further
      mechanistic investigation of the enzymatic CO reduction, while suggesting the
      potential of targeting both the protein scaffold and the cofactor species for
      nitrogenase-based applications in the future.

PMID- 29363248
TI  - A High-Fat Diet Rich in Saturated and Mono-Unsaturated Fatty Acids Induces
      Disturbance of Thyroid Lipid Profile and Hypothyroxinemia in Male Rats.
AB  - SCOPE: Increasing evidence has shown that the disturbance of lipid metabolism
      might make a possible contribution to the pathogenesis of organ dysfunction,
      including thyroid, yet it is unknown whether excess intake of dietary fat
      interferes in thyroid lipid profile. We investigate the effects of dietary fat
      toward the thyroid lipid profile and thyroid function. METHODS AND RESULTS: Male
      Sprague-Dawley rats are fed with high-fat diet (HFD) rich in saturated and mono
      unsaturated fatty acids or chow diet for 18 weeks. LC-MS analysis of thyroid
      shows that total free fatty acids (FFAs) content is significantly higher in HFD
      rats. The concentration of highly saturated triglycerides significantly increases
      in HFD rats, whereas the polyunsaturated triglyceride significantly decreases,
      indicating the decrease in unsaturation in the HFD group. Significant increase of
      lysophosphatidylcholines (LPC) is observed in HFD rats. Thyroid function tests
      show hypothyroxinemia (total thyroxine [TT4 ] and free thyroxine [FT4 ]) in HFD
      rats, and elevated thyrotropin (TSH) concentration. The HFD rats also show
      decreased thyroid uptake of iodine. CONCLUSION: Excess intake of dietary fat
      induces disturbance of thyroid lipid profile and hypothyroxinemia, indicating
      thyroid dysfunction. We speculate that it may provide a new prospect in
      understanding the pathogenesis of hypothyroidism.

PMID- 29363249
TI  - Pressure dressings in mastoid and middle ear surgery: are they necessary? A
      retrospective review of patient outcomes.
AB  - BACKGROUND: The application of mastoid pressure dressings following mastoid and
      middle ear surgery is widely practised to reduce the risk of haematoma and
      seroma. There are a number of minor morbidities associated with use of the
      dressings, as well as a financial cost associated with an overnight stay in
      hospital or a return appointment for removal of the dressings. The benefit of
      having these dressings in situ overnight is questionable. METHODS: A
      retrospective review of 133 patients who had their mastoid dressing removed 2 h
      after their procedure was undertaken at our Hospital. The patient records were
      scanned for procedure-related morbidities, and perioperative data were analysed.
      RESULTS: No haematomas or seromas occurred in any of the 133 patients studied.
      Minor morbidities associated with prolonged use of mastoid pressure dressings
      were avoided. CONCLUSION: Removal of mastoid pressure dressings 2 h following ear
      surgery is safe and effective. Furthermore, a mastoid dressing should not be a
      factor in the decision as to whether to treat a patient as a day case or
      overnight admission.

PMID- 29363251
TI  - Structural and luminescence properties of Sm3+ -doped bismuth phosphate glass for
      orange-red photonic applications.
AB  - In the present study, the effect of bismuth oxide (Bi2 O3 ) content on the
      structural and optical properties of 0.5Sm3+ -doped phosphate glass and the
      effect of concentration on structural and optical properties of Sm3+ -doped
      bismuth phosphate (BiP) glass were studied. Structural characterization was
      accomplished using X-ray diffraction (XRD), scanning electron microscopy (SEM)
      with energy dispersive spectroscopy (EDS), Fourier transform infrared (FTIR)
      spectroscopy and 31 P nuclear magnetic resonance (NMR) spectroscopy. Optical
      properties were studied using absorption, photoluminescence and decay
      measurements. Using optical absorption spectra, Judd-Ofelt parameters were
      derived to determine the local structure and bonding in the vicinity of Sm3+
      ions. The emission spectra of Sm3+ -doped BiP glass showed two intense emission
      bands, 4 G5/2 ->6 H7/2 (orange) and 4 G5/2 ->6 H9/2 (red) for which the
      stimulated emission cross-sections (sigmae ) and branching ratios (beta) were
      found to be higher. The quantum efficiencies were also calculated from decay
      measurements recorded for the 4 G5/2 level of Sm3+ ions. The suitable combination
      of Bi2 O3 (10 mol%) and Sm3+ (0.5 mol%) ions in these glasses acted as an
      efficient lasing material and might be suitable for the development of visible
      orange-red photonic materials.

PMID- 29363252
TI  - Fine Tuning of Antibiotic Activity by a Tailoring Hydroxylase in a Trans-AT
      Polyketide Synthase Pathway.
AB  - The addition or removal of hydroxy groups modulates the activity of many
      pharmacologically active biomolecules. It can be integral to the basic
      biosynthetic factory or result from associated tailoring steps. For the anti-MRSA
      antibiotic mupirocin, removal of a C8-hydroxy group late in the biosynthetic
      pathway gives the active pseudomonic acid A. An extra hydroxylation, at C4,
      occurs in the related but more potent antibiotic thiomarinol A. We report here in
      vivo and in vitro studies that show that the putative non-haem-iron(II)/alpha
      ketoglutaratedependent dioxygenase TmuB, from the thiomarinol cluster, 4
      hydroxylates various pseudomonic acids whereas C8-OH, and other substituents
      around the tetrahydropyran ring, block enzyme action but not substrate binding.
      Molecular modelling suggested a basis for selectivity, but mutation studies had a
      limited ability to rationally modify TmuB substrate specificity. 4-Hydroxylation
      had opposite effects on the potency of mupirocin and thiomarinol. Thus, TmuB can
      be added to the toolbox of polyketide tailoring technologies for the in vivo
      generation of new antibiotics in the future.

PMID- 29363250
TI  - Osimertinib in patients with epidermal growth factor receptor T790M advanced non
      small cell lung cancer selected using cytology samples.
AB  - Osimertinib is a potent, irreversible epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitor (TKI) selective for EGFR-TKI sensitizing (EGFRm) and
      T790M resistance mutations. The primary objective of the cytology cohort in the
      AURA study was to investigate safety and efficacy of osimertinib in pretreated
      Japanese patients with EGFR T790M mutation-positive non-small cell lung cancer
      (NSCLC), with screening EGFR T790M mutation status determined from cytology
      samples. The cytology cohort was included in the Phase I dose expansion component
      of the AURA study. Patients were enrolled based on a positive result of T790M by
      using cytology samples, and received osimertinib 80 mg in tablet form once daily
      until disease progression or until clinical benefit was no longer observed at the
      discretion of the investigator. Primary endpoint for efficacy was objective
      response rate (ORR) by investigator assessment. Twenty-eight Japanese patients
      were enrolled into the cytology cohort. At data cut-off (February 1, 2016), 12
      (43%) were on treatment. Investigator-assessed ORR was 75% (95% confidence
      interval [CI] 55, 89) and median duration of response was 9.7 months (95% CI 3.8,
      not calculable [NC]). Median progression-free survival was 8.3 months (95% CI
      4.2, NC) and disease control rate was 96% (95% CI 82, 100). The most common all
      causality adverse events were paronychia (46%), dry skin (46%), diarrhea (36%)
      and rash (36%). Osimertinib provided clinical benefit with a manageable safety
      profile in patients with pretreated EGFR T790M mutation-positive NSCLC whose
      screening EGFR T790M mutation-positive status was determined from cytology
      samples. (ClinicalTrials.gov number NCT01802632).

PMID- 29363253
TI  - Impact of primary care-initiated interventions promoting physical activity on
      body mass index: systematic review and meta-analysis.
AB  - INTRODUCTION: Physical inactivity is a risk factor for obesity, overweight and
      for a number of chronic diseases. Although primary care may be an ideal setting
      to encourage people to do more exercise, there are still significant gaps in the
      literature on the effectiveness of primary care-initiated policies to promote
      physical activity. METHODS: In this paper, we systematically review and meta
      analyse the evidence on the impact of primary care-initiated interventions to
      promote exercise on the body mass index and on physical activity energy
      expenditure levels among people at an increased risk of having potentially
      disabling non-communicable diseases (but healthy enough to exercise). RESULTS: We
      find that such interventions reduce body mass index by about 0.21 kg m-2 (95%
      confidence interval: -0.41 to -0.01) and increase physical activity-related
      energy expenditure (based mostly on self-recall) by about 1.77 metabolic
      equivalent of task-hours a week (95% confidence interval: 0.58 to 2.95).
      DISCUSSION: This study suggests that primary care-initiated interventions
      promoting physical activity can be an effective strategy to reduce weight and
      increase exercise levels in this population group, although the question remains
      about whether such interventions can be cost-effective.

PMID- 29363254
TI  - Hedgehog Antagonist Pyrimidine-Indole Hybrid Molecule Inhibits Ciliogenesis
      through Microtubule Destabilisation.
AB  - One of the crucial regulators of embryonic patterning and tissue development is
      the Hedgehog-glioma (Hh-Gli) signalling pathway; its uncontrolled activation has
      been implicated in different types of cancer in adult tissues. Primary cilium is
      one of the important factors required for the activation of Hh signalling, as it
      brings the critical components together for key protein-protein interactions
      required for Hh pathway regulation. Most of the synthetic and natural small
      molecule modulators of the pathway primarily antagonise Smoothened (Smo) or other
      effectors like Hh ligand or Gli. Here, we report a previously described Hh
      antagonist, with a pyrimidine-indole hybrid (PIH) core structure, as an inhibitor
      of ciliogenesis. The compound is unique in its mode of action, as it shows
      perturbation of microtubule dynamics in both cell-based assays and in vivo
      systems (zebrafish embryos). Further studies revealed that the probable targets
      are alpha-tubulin and its acetylated form, found in the cytoplasm and primary
      cilia. PIH also showed axonal defasiculation in developing zebrafish embryos. We
      thus propose that PIH antagonises Hh signalling by repressing cilia biogenesis
      and disassembling alpha-tubulin from its stabilised form.

PMID- 29363255
TI  - Health-related life satisfaction and its influencing factors: A cross-sectional
      study in China.
AB  - AIM: With the rapid development of science and technology, the pace of life has
      accelerated. Health and life satisfaction issues of persons are gaining more
      attention. China, Japan, Malaysia, and Taiwan conducted international cooperative
      research on health of four regional populations. This research was a part of the
      study in mainland China, which aimed to explore health-related life satisfaction
      and its influencing factors on large samples in mainland China. METHODS: A random
      group of 1404 persons from universities, factories, companies, and elderly
      centers in Changchun completed a structured questionnaire. This study centered on
      life satisfaction indicators, which included the current whole life, income,
      family relationships, peer relationships, relationships with the neighbors,
      living environment, personal health, family health, spare time, and housework
      share. Other collected data included the Body Mass Index, blood pressure, self
      rated health, Breslow's seven health practices, medical treatment within the past
      6 months, physical examinations, General Health Questionnaire (GHQ)-12 Scale,
      social activities, networking relationships with persons around the community,
      social support, and sociodemographic variables. Associations between life
      satisfaction, demographics, and health-related variables were analyzed through a
      multiway ANOVA. RESULTS: The living environment and income of Chinese persons
      were related to their low life satisfaction. The multiway ANOVA showed that the
      independent relationship of self-rated health, regular physical examinations, GHQ
      12 Scale, trust in the community, communication with the neighbors, education,
      and age related with life satisfaction accounting for 20.3% of the variance.
      Education and age showed interactive effects on life satisfaction. CONCLUSION:
      This study identified seven factors that influenced the life satisfaction of
      persons in mainland China. Life satisfaction can be enhanced through
      interventions to improve self-rated health, regular physical examinations, mental
      health, trust in the community, communication with the neighbors, education, and
      improvement in the health service.

PMID- 29363256
TI  - The retrosplenial cortex: A memory gateway between the cortical default mode
      network and the medial temporal lobe.
AB  - The default mode network (DMN) involves interacting cortical areas, including the
      posterior cingulate cortex (PCC) and the retrosplenial cortex (RSC), and
      subcortical areas, including the medial temporal lobe (MTL). The degree of
      functional connectivity (FC) within the DMN, particularly between MTL and medial
      parietal subsystems, relates to episodic memory (EM) processes. However, past
      resting-state studies investigating the link between posterior DMN-MTL FC and EM
      performance yielded inconsistent results, possibly reflecting heterogeneity in
      the degree of connectivity between MTL and specific cortical DMN regions. Animal
      work suggests that RSC has structural connections to both cortical DMN regions
      and MTL, and may thus serve as an intermediate layer that facilitates information
      transfer between cortical and subcortical DMNs. We studied 180 healthy old adults
      (aged 64-68 years), who underwent comprehensive assessment of EM, along with
      resting-state fMRI. We found greater FC between MTL and RSC than between MTL and
      the other cortical DMN regions (e.g., PCC), with the only significant association
      with EM observed for MTL-RSC FC. Mediational analysis showed that MTL-cortical
      DMN connectivity increased with RSC as a mediator. Further analysis using a graph
      theoretical approach on DMN nodes revealed the highest betweenness centrality for
      RSC, confirming that a high proportion of short paths among DMN regions pass
      through RSC. Importantly, the degree of RSC mediation was associated with EM
      performance, suggesting that individuals with greater mediation have an EM
      advantage. These findings suggest that RSC forms a critical gateway between MTL
      and cortical DMN to support EM in older adults.

PMID- 29363257
TI  - Rare differential for large bowel obstruction.

PMID- 29363258
TI  - ATF3 represses PINK1 gene transcription in lung epithelial cells to control
      mitochondrial homeostasis.
AB  - PINK1 (PTEN-induced putative kinase 1) is a key regulator of mitochondrial
      homeostasis that is relatively depleted in aging lungs and in lung epithelial
      cells from patients with idiopathic pulmonary fibrosis (IPF), a disease linked
      with aging. Impaired PINK1 expression and accumulation of damaged mitochondria in
      lung epithelial cells from fibrotic lungs were associated with the presence of ER
      stress. Here, we show that ATF3 (activating transcription factor 3), a member of
      the integrated stress response (ISR), negatively regulates transcription of the
      PINK1 gene. An ATF3 binding site within the human PINK1 promoter is located in
      the first 150 bp upstream of the transcription start site. Induction of ER stress
      or overexpression of ATF3 inhibited the activity of the PINK1 promoter.
      Importantly, overexpression of ATF3 causes accumulation of depolarized
      mitochondria, increased production of mitochondrial ROS, and loss of cell
      viability. Furthermore, conditional deletion of ATF3 in type II lung epithelial
      cells protects mice from bleomycin-induced lung fibrosis. Finally, we observed
      that ATF3 expression increases in the lung with age and, specially, in lung
      epithelial cells from IPF lungs. These data provide a unique link between ATF3
      and PINK1 expression suggesting that persistent stress, driven by ATF3, can
      dysregulate mitochondrial homeostasis by repression of PINK1 mRNA synthesis.

PMID- 29363259
TI  - Comparative efficacy of two anti-aging products containing retinyl palmitate in
      healthy human volunteers.
AB  - BACKGROUND: No study yet described the comparative efficacy of two over-the
      counter (OTC) anti-aging products in Asian subjects using the techniques
      involving analysis of living skin. AIM: We sought to evaluate the anti-aging
      efficacy of two commercial formulations containing retinyl palmitate using a high
      resolution UVA video camera. METHOD: Total 11 healthy male volunteers, agreed to
      participate in this single-blind split-face design study with the mean age of
      25.5 years. Every night, volunteers applied one type of cream on the left side
      and other type of cream on the right side of the face, as directed according to
      the study design for 60 days. Measurements of the parameters were taken at 0,
      1st, 7th, 15th, 30th, and 60th day of study period using noninvasive UVA video
      camera Visioscan(r) VC98. Cream applied on right side of the face labeled as "R"
      and on the left side as "L." RESULTS: Sixty-day use of the creams showed
      significant improvement in SELS parameters of the skin. Percent change in skin
      wrinkling (SEw) parameter calculated after 60 days was -6.68% after applying
      cream R and -8.27% after applying cream L. CONCLUSION: We concluded that
      constituents in both creams have potentially influenced skin surface parameters,
      thus indicating that, these creams as a better option to lessen the effects of
      aging on facial skin on long-term application.

PMID- 29363260
TI  - New adaptive statistical iterative reconstruction ASiR-V: Assessment of noise
      performance in comparison to ASiR.
AB  - PURPOSE: To assess the noise characteristics of the new adaptive statistical
      iterative reconstruction (ASiR-V) in comparison to ASiR. METHODS: A water phantom
      was acquired with common clinical scanning parameters, at five different levels
      of CTDIvol . Images were reconstructed with different kernels (STD, SOFT, and
      BONE), different IR levels (40%, 60%, and 100%) and different slice thickness
      (ST) (0.625 and 2.5 mm), both for ASiR-V and ASiR. Noise properties were
      investigated and noise power spectrum (NPS) was evaluated. RESULTS: ASiR-V
      significantly reduced noise relative to FBP: noise reduction was in the range 23%
      60% for a 0.625 mm ST and 12%-64% for the 2.5 mm ST. Above 2 mGy, noise reduction
      for ASiR-V had no dependence on dose. Noise reduction for ASIR-V has dependence
      on ST, being greater for STD and SOFT kernels at 2.5 mm. For the STD kernel ASiR
      V has greater noise reduction for both ST, if compared to ASiR. For the SOFT
      kernel, results varies according to dose and ST, while for BONE kernel ASIR-V
      shows less noise reduction. NPS for CT Revolution has dose dependent behavior at
      lower doses. NPS for ASIR-V and ASiR is similar, showing a shift toward lower
      frequencies as the IR level increases for STD and SOFT kernels. The NPS is
      different between ASiR-V and ASIR with BONE kernel. NPS for ASiR-V appears to be
      ST dependent, having a shift toward lower frequencies for 2.5 mm ST. CONCLUSIONS:
      ASiR-V showed greater noise reduction than ASiR for STD and SOFT kernels, while
      keeping the same NPS. For the BONE kernel, ASiR-V presents a completely different
      behavior, with less noise reduction and modified NPS. Noise properties of the
      ASiR-V are dependent on reconstruction slice thickness. The noise properties of
      ASiR-V suggest the need for further measurements and efforts to establish new CT
      protocols to optimize clinical imaging.

PMID- 29363261
TI  - The Oral Bioavailability of 8-Prenylnaringenin from Hops (Humulus Lupulus L.) in
      Healthy Women and Men is Significantly Higher than that of its Positional Isomer
      6-Prenylnaringenin in a Randomized Crossover Trial.
AB  - SCOPE: Prenylated chalcones and flavonoids from hop (Humulus lupulus L.), such as
      6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), are investigated for
      their health beneficial and anticancer activities. We, thus, compare the oral
      bioavailability and safety of 6-PN and 8-PN in healthy young women and men, and
      investigated their effects on peripheral blood mononuclear cells (PBMC). METHODS
      AND RESULTS: A double-blind, placebo-controlled, crossover trial is conducted
      with 16 healthy volunteers (eight women, eight men) given a single oral dose of
      500 mg 6-PN, 8-PN, or placebo in random order. Maximum total concentrations of 6
      PN and 8-PN in plasma (Cmax ; 543 and 2834 nmol L-1 ) and their respective area
      under the plasma concentration-time curve (AUC; 3635 and 15801 nmol L-1 * h) are
      significantly (5.2- and 4.3-fold) higher for 8-PN than for 6-PN (p ? 0.05). PBMC
      for ex vivo experiments are isolated from blood sampled before and 6 h after
      intake of 6-PN, 8-PN, or placebo. Despite the single-treatment regime and low
      blood concentrations, both 6-PN and 8-PN increase the survival of PBMC relative
      to control. CONCLUSION: 8-PN is significantly more bioavailable in healthy humans
      than its isomer 6-PN. Interestingly, 6-PN, despite being less bioavailable, is
      similarly effective as 8-PN in enhancing PBMC viability.

PMID- 29363263
TI  - Art, music, story: The evaluation of a person-centred arts in health programme in
      an acute care older persons' unit.
AB  - AIMS AND OBJECTIVES: To evaluate the impact of an arts in health programme
      delivered by a specialised artist within an acute older person's unit.
      BACKGROUND: Acute hospitals must meet the increasingly complex needs of older
      people who experience multiple comorbidities, often including cognitive
      impairment, either directly related to their admission or longer term conditions,
      including dementia. A focus on physical illness, efficiency and tasks within an
      acute care environment can all divert attention from the psychosocial well-being
      of patients. This focus also decreases capacity for person-centred approaches
      that acknowledge and value the older person, their life story, relationships and
      the care context. The importance of arts for health and wellness, including
      responsiveness to individual need, is well established: however, there is little
      evidence about its effectiveness for older people in acute hospital settings. We
      report on a collaborative arts in health programme on an acute medical ward for
      older people. DESIGN: The qualitative study used collaborative enquiry
      underpinned by a constructivist approach to evaluate an arts programme that
      involved participatory art-making activities, customised music, song and
      illustration work, and enlivening the unit environment. METHODS: Data sources
      included observation of art activities, semi-structured interviews with patients
      and family members, and focus groups with staff. Data were transcribed and
      thematically analysed using a line by line approach. RESULTS: The programme had
      positive impacts for the environment, patients, families and staff. The
      environment exhibited changes as a result of programme outputs; patients and
      families were engaged and enjoyed activities that aided recovery from illness;
      and staff also enjoyed activities and importantly learnt new ways of working with
      patients. CONCLUSIONS: An acute care arts in health programme is a carefully
      nuanced programme where the skills of the arts health worker are critical to
      success. Utilising such skill, continued focus on person-centeredness and
      openness to creativity demonstrated positive impacts for patients, families,
      staff and the ward environment. IMPLICATIONS FOR PRACTICE: This study affirms the
      contribution of an arts in health program for older persons in an acute care
      setting in challenging the dominance of a task based medical model and
      emphasising person-centred care and outcomes.

PMID- 29363262
TI  - Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan.
AB  - Gout is an inflammatory disease manifested by the deposition of monosodium urate
      (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues.
      Gout is not a new disease, which was first documented nearly 5,000 years ago. The
      prevalence of gout has increased globally in recent years, imposing great disease
      burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a
      variety of comorbidities, including cardiovascular diseases, chronic kidney
      disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid
      dysfunction, and psoriasis. To prevent acute arthritis attacks and complications,
      earlier use of pharmacotherapeutic treatment should be considered, and patients
      with hyperuricemia and previous episodes of acute gouty arthritis should receive
      long-term urate-lowering treatment. Urate-lowering drugs should be used during
      the inter-critical and chronic stages to prevent recurrent gout attacks, which
      may elicit gradual resolution of tophi. The goal of urate-lowering therapy should
      aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi,
      the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi
      dissolution. The goal of this consensus paper was to improve gout and
      hyperuricemia management at a more comprehensive level. The content of this
      consensus paper was developed based on local epidemiology and current clinical
      practice, as well as consensuses from two multidisciplinary meetings and
      recommendations from Taiwan Guideline for the Management of Gout and
      Hyperuricemia.

PMID- 29363264
TI  - Canine spinal meningiomas and nerve sheath tumours in 34 dogs (2008-2016):
      Distribution and long-term outcome based upon histopathology and treatment
      modality.
AB  - The purpose of this retrospective, multicentre case series was to describe the
      outcome following surgery and/or radiation of spinal meningiomas and nerve sheath
      tumours (NSTs) based upon treatment modality, with a specific aim to evaluate the
      survival times and time to recurrence following treatment for each
      histopathological diagnosis. Our hypothesis was that the addition of radiation
      therapy modalities to treatment will yield longer time to recurrence of clinical
      signs and survival time. Thirty-four dogs met the inclusion criteria of
      histopathologically diagnosed extramedullary spinal meningioma or NST. Sixteen
      extramedullary spinal meningiomas and 18 NSTs were diagnosed. A diagnosis of
      meningioma was associated with a significantly longer survival time compared with
      NSTs, with median survival times (MST) of 508 days (95% confidence interval [CI]:
      66-881) vs 187 days (95% CI: 76-433; P = .02). Dogs (seven) treated with
      stereotactic radiation therapy (SRT) for recurrence after surgery alone or SRT
      alone as their initial treatment gained an additional 125 to 346 days survival
      time.

PMID- 29363265
TI  - Morale, stress and coping strategies of staff working in the emergency
      department: A comparison of two different-sized departments.
AB  - OBJECTIVE: Clinical staff in EDs are subject to a range of stressors. The
      objective of this study was to describe and compare clinical staff perceptions of
      their ED's working environment across two different Australian EDs. METHODS: This
      was a cross-sectional, descriptive, research design that included distribution of
      three survey tools to clinical staff in two Australian EDs in 2016. Descriptive
      statistics were reported to characterise workplace stressors, coping styles and
      the ED environment. These data were compared by hospital and the employee's
      clinical role (nurse or physician). RESULTS: In total, 146 ED nurses and doctors
      completed the survey (response rate: 67%). Despite geographical variation, the
      staff at the two locations had similar demographic profiles in terms of age, sex
      and years of experience. Staff reported moderate levels of workload and self
      realisation but low levels of conflict or nervousness in the workplace. Nurses
      and physicians reported similar perceptions of the work environment, although
      nurses reported slightly higher median levels of workload. Staff rated the death
      or sexual abuse of a child as most stressful, followed by workplace violence and
      heavy workload. Staff used a large range of coping strategies, and these were
      similar across both sites. CONCLUSION: These findings are the first multi-site
      and multidisciplinary examinations of Australian ED staff perceptions, improving
      our understanding of staff stressors and coping strategies and highlighting
      similarities across different EDs. These data support the development and
      implementation of strategies to improve ED working environments to help ensure
      professional longevity of ED staff.

PMID- 29363266
TI  - Association between maternal body mass index and congenital heart defects in
      infants: A meta-analysis.
AB  - We conducted this meta-analysis to address the open question of a possible
      association between maternal body mass index (BMI) and congenital heart defects
      (CHDs) in infants. We conducted a comprehensive computerized search of PubMed,
      Web of Science, Medline, and Embase databased (January 1980 through August 2017).
      We assessed the association between maternal BMI and the risk for congenital
      heart defects in their offspring. Study-specific relative risk estimates were
      polled according to random-effect or fixed-effect models. From 2567 citations, a
      total of 13 case-control studies and 4 cohort studies were selected for a meta
      analysis, including more than 1 150 000 cases. The pooled odds radio (OR) of
      1.065 (95% confidence interval [CI], 1.021-1.100; P = .001; I2 = 60.1%) indicated
      a positive effect of maternal overweight status (BMI 25.0-29.9 kg/m2 ) on the
      risk for congenital heart defects in infants. Moreover, we observed a significant
      association between maternal obesity (BMI >= 30 kg/m2 ) and congenital heart
      defects in their offspring (OR: 1.174; 95% CI, 1.146-1.203, P = 0.161; I2
      =25.5%). However, there was little significant evidence of an association between
      maternal underweight status (BMI < 18.5 kg/m2 ) and offspring with congenital
      heart defects, and the pooled OR was 1.015 (95% CI, 0.980-1.052; P = 0.085; I2
      =34.0%). Our meta-analysis provides robust evidence of the positive association
      between maternal BMI and the risk for fetal congenital heart defects.

PMID- 29363267
TI  - DNA-damage inducible protein 1 is a conserved metacaspase substrate that is
      cleaved and further destabilized in yeast under specific metabolic conditions.
AB  - Metacaspases, distant relatives of metazoan caspases, have been shown to
      participate in programmed cell death in plants and in progression of the cell
      cycle and removal of protein aggregates in unicellular eukaryotes. However, since
      natural proteolytic substrates have scarcely been identified to date, their roles
      in these processes remain unclear. Here, we report that the DNA-damage inducible
      protein 1 (Ddi1) represents a conserved protein substrate for metacaspases
      belonging to divergent unicellular eukaryotes (trypanosomes and yeasts). We show
      that although the recognized cleavage sequence is not identical among the
      different model organisms tested, in all of them the proteolysis consequence is
      the removal of the ubiquitin-associated domain (UBA) present in the protein. We
      also demonstrate that Ddi1 cleavage is tightly regulated in vivo as it only takes
      place in yeast when calcium increases but under specific metabolic conditions.
      Finally, we show that metacaspase-mediated Ddi1 cleavage reduces the stability of
      this protein which can certainly impact on the many functions ascribed for it,
      including shuttle to the proteasome, cell cycle control, late secretory pathway
      regulation, among others.

PMID- 29363268
TI  - Synthesis of Two-Electron Bimetallic Cu-Ag and Cu-Au Clusters by using [Cu13 (S2
      CNn Bu2 )6 (C=CPh)4 ]+ as a Template.
AB  - Atomically precise Cu-rich bimetallic superatom clusters have been synthesized by
      adopting a galvanic exchange strategy. [Cu@Cu12 (S2 CNn Bu2 )6 (C=CPh)4 ][CuCl2 ]
      (1) was used as a template to generate compositionally uniform clusters [M@Cu12
      (S2 CNn Bu2 )6 (C=CPh)4 ][CuCl2 ], where M=Ag (2), Au (3). Structures of 1, 2 and
      3 were determined by single crystal X-ray diffraction and the results were
      supported by ESI-MS. The anatomies of clusters 1-3 are very similar, with a
      centred cuboctahedral cationic core that is surrounded by six di
      butyldithiocarbamate (dtc) and four phenylacetylide ligands. The doped Ag and Au
      atoms were found to preferentially occupy the centre of the 13-atom cuboctahedral
      core. Experimental and theoretical analyses of the synthesized clusters revealed
      that both Ag and Au doping result in significant changes in cluster stability,
      optical characteristics and enhancement in luminescence properties.

PMID- 29363270
TI  - Staff personhood in dementia care settings: "Do they care about me?"
AB  - AIMS AND OBJECTIVES: This article aims to examine RCAs' own experiences of
      personhood in dementia care settings. BACKGROUND: Conceptually, person-centred
      care entails fostering the personhood of residents and the residential care aides
      (RCAs) who provide much of their hands-on care. To date, however, staff
      personhood has been overlooked in the empirical literature. DESIGN: The study was
      part of a larger focused ethnographic project exploring how the organisational
      care environment impedes or facilitates the provision of quality dementia care.
      METHODS: Semi-structured interviews with 23 RCAs and more than 230 hours of
      participant observation were conducted in two nursing homes with specialised
      dementia units in British Columbia, Canada. RESULTS: Two overarching themes,
      "personhood undermined-management-staff relations" and "personhood undermined
      workplace policies and practices" emerged, illustrating how, despite exposure to
      features believed beneficial to their working environment (e.g., favourable
      staffing ratios, relatively good remuneration), RCAs encountered repeated
      affronts to their personhood. The first theme encompasses the importance of being
      known (i.e., as persons and of their job demands) and valued (i.e., appreciated
      for their work in non-monetary terms). The second highlights the salience of work
      life balance, full-staffing coverage and supportive human resource practices.
      CONCLUSIONS: RCAs' experiences reveal how the ongoing search for cost
      efficiencies, cost-containment and cost-accountability overshadows their
      individuality, indicating a key disconnect between conceptual ideals and
      workplace realities. IMPLICATIONS FOR PRACTICE: Organisations are encouraged to
      consider creating person-centred management and workplace practices that provide
      tangible evidence that RCAs, and their work, matter.

PMID- 29363269
TI  - Measuring fibrinolysis: from research to routine diagnostic assays.
AB  - Development and standardization of fibrinolysis methods have progressed more
      slowly than coagulation testing and routine high-throughput screening tests for
      fibrinolysis are still lacking. In laboratory research, a variety of approaches
      are available and are applied to understand the regulation of fibrinolysis and
      its contribution to the hemostatic balance. Fibrinolysis in normal blood is slow
      to develop. For practical purposes plasminogen activators can be added to
      clotting plasma, or euglobulin prepared to reduce endogenous inhibitors, but
      results are complicated by these manipulations. Observational studies to identify
      a 'fibrinolysis deficit' have concluded that excess fibrinolysis inhibitors,
      plasminogen activator inhibitor 1 (PAI-1) or thrombin-activatable fibrinolysis
      inhibitor (TAFI), zymogen or active enzyme, may be associated with an increased
      risk of thrombosis. However, results are not always consistent and problems of
      adequate standardization are evident with these inhibitors and also for
      measurement of fibrin degradation products (D-dimer). Few methods are available
      to investigate fibrinolysis under flow, or in whole blood, but viscoelastic
      methods (VMs) such as ROTEM and TEG do permit the contribution of cells, and
      importantly platelets, to be explored. VMs are used to diagnose clinical
      hyperfibrinolysis, which is associated with high mortality. There is a debate on
      the usefulness of VMs as a point-of-care test method, particularly in trauma.
      Despite the difficulties of many fibrinolysis methods, research on the
      fibrinolysis system, taking in wider interactions with hemostasis proteins, is
      progressing so that in future we may have more complete models and better
      diagnostic methods and therapeutics.

PMID- 29363272
TI  - Microbiota in obesity: interactions with enteroendocrine, immune and central
      nervous systems.
AB  - Western diets, with high consumption of simple sugars and saturated fats,
      contribute to the rise in the prevalence of obesity. It now seems clear that high
      fat diets cause obesity, at least in part, by modifying the composition and
      function of the microorganisms that colonize in the gastrointestinal tract, the
      microbiota. The exact pathways by which intestinal microbiota contribute to
      obesity remain largely unknown. High-fat diet-induced alterations in intestinal
      microbiota have been suggested to increase energy extraction, intestinal
      permeability and systemic inflammation while decreasing the capability to
      generate obesity-suppressing short-chain fatty acids. Moreover, by increasing
      systemic inflammation, microglial activation and affecting vagal nerve activity,
      'obese microbiota' indirectly influence hypothalamic gene expression and promote
      overeating. Because the potential of intestinal microbiota to induce obesity has
      been recognized, multiple ways to modify its composition and function are being
      investigated to provide novel preventive and therapeutic strategies against diet
      induced obesity.

PMID- 29363271
TI  - From laboratory to point of entry: development and implementation of a loop
      mediated isothermal amplification (LAMP)-based genetic identification system to
      prevent introduction of quarantine insect species.
AB  - BACKGROUND: Rapid genetic on-site identification methods at points of entry, such
      as seaports and airports, have the potential to become important tools to prevent
      the introduction and spread of economically harmful pest species that are
      unintentionally transported by the global trade of plant commodities. This paper
      reports the development and evaluation of a loop-mediated isothermal
      amplification (LAMP)-based identification system to prevent introduction of the
      three most frequently encountered regulated quarantine insect species groups at
      Swiss borders, Bemisia tabaci, Thrips palmi and several regulated fruit flies of
      the genera Bactrocera and Zeugodacus. RESULTS: The LAMP primers were designed to
      target a fragment of the mitochondrial cytochrome c oxidase subunit I gene and
      were generated based on publicly available DNA sequences. Laboratory evaluations
      analysing 282 insect specimens suspected to be quarantine organisms revealed an
      overall test efficiency of 99%. Additional on-site evaluation at a point of entry
      using 37 specimens performed by plant health inspectors with minimal laboratory
      training resulted in an overall test efficiency of 95%. During both evaluation
      rounds, there were no false-positives and the observed false-negatives were
      attributable to human-induced manipulation errors. To overcome the possibility of
      accidental introduction of pests as a result of rare false-negative results,
      samples yielding negative results in the LAMP method were also subjected to DNA
      barcoding. CONCLUSION: Our LAMP assays reliably differentiated between the tested
      regulated and non-regulated insect species within <1 h. Hence, LAMP assays
      represent suitable tools for rapid on-site identification of harmful pests, which
      might facilitate an accelerated import control process for plant commodities. (c)
      2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on
      behalf of Society of Chemical Industry.

PMID- 29363273
TI  - Preparation and evaluation of effect on Escherichia coli and Staphylococcus
      aureus of radiolabeled ampicillin-loaded graphene oxide nanoflakes.
AB  - Ampicillin is a one of effective antibiotics against Gram-positive and Gram
      negative bacteria. This study aimed to label ampicillin-loaded graphene oxide
      nanoflake (AMP-GO) with 99m Tc and evaluate of its in vitro binding to
      Staphylococcus aureus and Escherichia coli. Firstly, ampicillin was loaded into
      graphene oxide nanoflake prepared. AMP-GO was characterized by Fourier transform
      infrared spectroscopy (FTIR) and scanning electron microscope (SEM) techniques,
      and the amount of loaded ampicillin onto GO was determined by UV-Vis absorption
      spectroscopy. AMP and AMP-GO were labeled with 99m Tc using stannous chloride
      reducing agent. Labeling efficiency of 99m Tc-AMP-GO was found to be 97.66 +/-
      2.06%. 99m Tc-AMP-GO has higher binding efficiencies to both S. aureus and E.
      coli than 99m Tc-AMP. 99m Tc-AMP-GO could be promising candidate as agent
      infection nuclear imaging. Furthermore, in vivo studies of 99m Tc-AMP-GO with
      infected rats are planned to be performed.

PMID- 29363274
TI  - In silico identification, synthesis and biological evaluation of novel tetrazole
      inhibitors of MurB.
AB  - In the context of antibacterial drug discovery resurgence, novel therapeutic
      targets and new compounds with alternative mechanisms of action are of paramount
      importance. We focused on UDP-N-acetylenolpyruvylglucosamine reductase (i.e.
      MurB), an underexploited target enzyme that is involved in early steps of
      bacterial peptidoglycan biosynthesis. On the basis of the recently reported
      crystal structure of MurB in complex with NADP+ , a pharmacophore model was
      generated and used in a virtual screening campaign with combined structure-based
      and ligand-based approaches. To explore chemical space around hit compounds,
      further similarity search and organic synthesis were employed to obtain several
      compounds with micromolar IC50 values on MurB. The best inhibitors in the
      reported series of 5-substituted tetrazol-2-yl acetamides were compounds 13, 26
      and 30 with IC50 values of 34, 28 and 25 MUm, respectively. None of the reported
      compounds possessed in vitro antimicrobial activity against Staphylococcus aureus
      and Escherichia coli.

PMID- 29363275
TI  - Functional study of a novel missense single-nucleotide variant of NUP107 in two
      daughters of Mexican origin with premature ovarian insufficiency.
AB  - BACKGROUND: Hypergonadotropic hypogonadism (HH) is a genetically heterogeneous
      disorder that usually presents with amenorrhea, atrophic ovaries, and low
      estrogen. Most cases of HH are idiopathic and nonsyndromic. Nucleoporin 107
      (NUP107), a protein involved in transport between cytoplasm and nucleus with
      putative roles in meiosis/mitosis progression, was recently implicated as a cause
      of HH. We identified a NUP107 genetic variant in a nonconsanguineous family with
      two sisters affected with primary amenorrhea and HH, and generated a mouse model
      that carried the human variant. METHODS: We performed a high-resolution X
      chromosome microarray and whole exome sequencing on parents and two sisters with
      HH to identify pathogenic variants. We generated a mouse model of candidate
      NUP107 variant using CRISPR/Cas9. RESULTS: Whole exome sequencing identified a
      novel and rare missense variant in the NUP107 gene (c.1063C>T, p.R355C) in both
      sisters with HH. In order to determine functional significance of this variant,
      we used CRISPR/Cas9 to introduce the human variant into the mouse genome. Mice
      with the homolog of the R355C variant, as well as the nine base pairs deletion in
      Nup107 had female subfertility. CONCLUSIONS: Our findings indicate that NUP107
      R355C variant falls in the category of variant of unknown significance as the
      cause of HH and infertility.

PMID- 29363276
TI  - "Candidatus Neoehrlichia chilensis" sp. nov.: Molecular detection and
      characterization of a novel Anaplasmataceae in wild rodents from Valdivia,
      southern Chile.
AB  - This study aimed to screen wild rodents from southern Chile, for the presence of
      Anaplasmatacea. Spleen samples from 33 wild rodents trapped in Valdivia Province
      were screened by conventional PCR (cPCR), targeting the Anaplasmataceae 16S rRNA
      gene (16S). Positive samples were further evaluated, targeting a larger 16S
      fragment, groEL operon, and gltA gene, followed by sequencing and phylogenetic
      analysis. Anaplasmataceae DNA was detected in 15% (five of 33) of the tested
      rodents (Abrothrix sp. [four of five] and Mus musculus [one of five]). Analysis
      of sequenced products based on the 16S gene revealed high similarity with "Ca.
      Neoehrlichia mikurensis," "Ca. Neoehrlichia lotoris" and "Ca. Neoehrlichia
      arcana" (97.8%-98.6%). A lower similarity was observed with Candidatus
      Neoehrlichia groEL (89.7%-92%) and gltA (79.5%-79.9%) loci. According to the
      16SrRNA, groEL and gltA phylogenetic analyses, two closely related genotypes of
      "Candidatus Neoehrlichia" spp. from Chile were observed, which clustered together
      in a separate clade from other species in this genus. This study suggests the
      presence of two genotypes of a novel species of "Candidatus Neoehrlichia,"
      proposed as "Candidatus Neoehrlichia chilensis," circulating in rodents from
      Chile. This is the first report of "Ca. Neoehrlichia" species in rodents from
      America.

PMID- 29363277
TI  - Dietary approach to stop hypertension diet and cardiovascular risk factors among
      10- to 18-year-old individuals.
AB  - BACKGROUND: Current evidence available on the association between Dietary
      Approach to Stop Hypertension (DASH) diet and cardiovascular risk in adolescents
      is controversial. OBJECTIVE: The aim of the present study was to assess the
      association between DASH diet and cardiovascular risk factors after 3 years of
      follow-up among Tehranian adolescents. METHODS: A population-based cohort study
      was conducted on 628 subjects, aged 10-18 years, selected from among participants
      of the Tehran Lipid and Glucose Study. The DASH score was determined on the basis
      of eight components using a valid and reliable food-frequency questionnaire at
      baseline. Anthropometric and lipid profile data were measured at baseline and
      after a 3-year follow-up. RESULTS: Mean (SD) age of the study population (46.6%
      men) was 14.1 (2.5) years. After adjustment for potential confounding variables,
      including sex, age, physical activity and total calorie intake, the risk of
      general obesity (OR = 0.26, 95%CI: 0.15-0.76) and central obesity (OR = 0.32,
      95%CI: 0.14-0.84) in the highest quintile of DASH score were significantly lower
      than in subjects in the lowest quintile. However, DASH score was not associated
      with risk of incident dyslipidaemia in our study (OR = 0.81, 95%CI: 0.30-1.82).
      The higher DASH score was inversely associated with 3-year changes in body mass
      index and waist circumference during the study period (P for trend <0.05).
      However, there was no significant association between the higher score of this
      diet with 3-year changes in lipid profiles. CONCLUSION: Adherence to the DASH
      diet was associated with decreased risk of central and general obesity, whereas
      higher DASH diet score was not associated with risk of dyslipidaemia in
      adolescents.

PMID- 29363278
TI  - Aromatic Polyimide/Graphene Composite Organic Cathodes for Fast and Sustainable
      Lithium-Ion Batteries.
AB  - A composite organic cathode material based on aromatic polyimide (PI) and highly
      conductive graphene was prepared through a facile in situ polymerization method
      for application in lithium-ion batteries. The in situ polymerization generated
      intimate contact between PI and electronically conductive graphene, resulting in
      conductive composites with highly reversible redox reactions and good structure
      stability. The synergistic effect between PI and graphene enabled not only a high
      reversible capacity of 232.6 mAh g-1 at a charge-discharge rate of C/10 but also
      exceptionally high-rate cycling stability, that is, a high capacity of 108.9 mAh
      g-1 at a very high charge-discharge rate of 50C with a capacity retention of 80 %
      after 1000 cycles. This improved electrochemical performance resulted from the
      combination of stable redox reversibility of PI and high electronic conductivity
      of the graphene additive. The graphene-based composite also exhibited much better
      performance than composites based on multi-walled carbon nanotubes and the
      conductive carbon black C45 in terms of specific capacity and long-term cycling
      stability under the same charge-discharge rates.

PMID- 29363279
TI  - An Egyptian HPAI H5N1 isolate from clade 2.2.1.2 is highly pathogenic in an
      experimentally infected domestic duck breed (Sudani duck).
AB  - The highly pathogenic avian influenza (HPAI) H5N1 viruses continue to cause major
      problems in poultry and can, although rarely, cause human infection. Being
      enzootic in domestic poultry, Egyptian isolates are continuously evolving, and
      novel clades vary in their pathogenicity in avian hosts. Considering the
      importance of domestic ducks as natural hosts of HPAI H5N1 viruses and their
      likelihood of physical contact with other avian hosts and humans, it is of utmost
      importance to characterize the pathogenicity of newly emerged HPAI strains in the
      domestic duck. The most recently identified Egyptian clade 2.2.1.2 HPAI H5N1
      viruses have been isolated from naturally infected pigeons, turkeys and humans.
      However, essentially nothing is known about their pathogenicity in domestic
      ducks. We therefore characterized the pathogenicity of an Egyptian HPAI H5N1
      isolate A/chicken/Faquos/amn12/2011 (clade 2.2.1.2) in Sudani duck, a domestic
      duck breed commonly reared in Egypt. While viral transcription (HA mRNA) was
      highest in lung, heart and kidney peaking between 40 and 48 hpi, lower levels
      were detected in brain. Weight loss of infected ducks started at 16 hpi and
      persisted until 120 hpi. The first severe clinical signs were noted by 32 hpi and
      peaked in severity at 72 and 96 hpi. Haematological analyses showed a decline in
      total leucocytes, granulocytes, platelets and granulocyte/lymphocyte ratio, but
      lymphocytosis. Upon necropsy, lesions were obvious in heart, liver, spleen and
      pancreas and consisted mainly of necrosis and petechial haemorrhage.
      Histologically, lungs were the most severely affected organs, whereas brain only
      showed mild neuronal degeneration and gliosis at 48 hpi despite obvious
      neurological clinical signs. Taken together, our results provide first evidence
      that this HPAI H5N1 isolate (clade 2.2.1.2) is highly pathogenic to Sudani ducks
      and highlight the importance of this breed as potential reservoir and
      disseminator of HPAI strains from this clade.

PMID- 29363280
TI  - Disparities in Total Knee Replacement: Population Losses in Quality-Adjusted Life
      Years Due to Differential Offer, Acceptance, and Complication Rates for African
      Americans.
AB  - OBJECTIVE: Total knee replacement (TKR) is an effective treatment for end-stage
      knee osteoarthritis (OA). American racial minorities undergo fewer TKRs than
      whites. We estimated quality-adjusted life-years (QALYs) lost for African
      American knee OA patients due to differences in TKR offer, acceptance, and
      complication rates. METHODS: We used the Osteoarthritis Policy Model, a computer
      simulation of knee OA, to predict QALY outcomes for African American and white
      knee OA patients with and without TKR. We estimated per-person QALYs gained from
      TKR as the difference between QALYs with current TKR use and QALYs when no TKR
      was performed. We estimated average, per-person QALY losses in African Americans
      as the difference between QALYs gained with white rates of TKR and QALYs gained
      with African American rates of TKR. We calculated population-level QALY losses by
      multiplying per-person QALY losses by the number of persons with advanced knee
      OA. Finally, we estimated QALYs lost specifically due to lower TKR offer and
      acceptance rates and higher rates of complications among African American knee OA
      patients. RESULTS: African American men and women gain 64,100 QALYs from current
      TKR use. With white offer and complications rates, they would gain an additional
      72,000 QALYs. Because these additional gains are unrealized, we call this a loss
      of 72,000 QALYs. African Americans lose 67,500 QALYs because of lower offer
      rates, 15,800 QALYs because of lower acceptance rates, and 2,600 QALYs because of
      higher complication rates. CONCLUSION: African Americans lose 72,000 QALYs due to
      disparities in TKR offer and complication rates. Programs to decrease disparities
      in TKR use are urgently needed.

PMID- 29363281
TI  - Detection and genetic characterization of porcine deltacoronavirus in Tibetan
      pigs surrounding the Qinghai-Tibet Plateau of China.
AB  - Porcine deltacoronavirus (PDCoV) is a recently discovered RNA virus that belongs
      to the family Coronaviridae and genus Deltacoronavirus. This virus causes enteric
      disease in piglets that is characterized by enteritis and diarrhoea. In our
      present investigation, 189 diarrhoeic samples were collected between July 2016
      and May 2017 from Tibetan pigs inhabiting in three different provinces
      surrounding the Qinghai-Tibet Plateau of China. We then applied the molecular
      based method of reverse transcription polymerase chain reactions (RT-PCRs) to
      detect the presence of PDCoV in collected samples, and RT-PCR indicated that the
      prevalence of PDCoV was 3.70% (7/189) in Tibetan pigs. Four of 7 PDCoV-positive
      pigs were monoinfections of PDCoV, three samples were co-infections of PDCoV with
      porcine epidemic diarrhoea virus (PEDV), and 52 (27.51%) samples were positive
      for PEDV. Four strains with different full-length genomes were identified
      (CHN/GS/2016/1, CHN/GS/2016/2, CHN/GS-/2017/1 and CHN/QH/2017/1), and their
      genomes were used to analyse the characteristics of PDCoV currently prevalent in
      Tibetan pigs. We found a 3-nt insertion in the spike gene in four strains in
      Tibetan pigs. Phylogenetic analysis of the complete genome and spike and
      nucleocapsid gene sequences revealed that these strains shared ancestors with the
      strain CHN-AH-2004, which was found in pigs from the Anhui province of China
      mainland. However, PDCoV strains from Tibetan pigs formed different branches
      within the same cluster, implying continuous evolution in the field. Our present
      findings highlight the importance of epidemiologic surveillance to limit the
      spread of PDCoV in livestock at high altitudes in China.

PMID- 29363282
TI  - To frame or not to frame? Cone-beam CT-based analysis of head immobilization
      devices specific to linac-based stereotactic radiosurgery and radiotherapy.
AB  - PURPOSE: Noninvasive frameless systems are increasingly being utilized for head
      immobilization in stereotactic radiosurgery (SRS). Knowing the head positioning
      reproducibility of frameless systems and their respective ability to limit
      intrafractional head motion is important in order to safely perform SRS. The
      purpose of this study was to evaluate and compare the intrafractional head motion
      of an invasive frame and a series of frameless systems for single fraction SRS
      and fractionated/hypofractionated stereotactic radiotherapy (FSRT/HF-SRT).
      METHODS: The noninvasive PinPoint system was used on 15 HF-SRT and 21 SRS
      patients. Intrafractional motion for these patients was compared to 15 SRS
      patients immobilized with Cosman-Roberts-Wells (CRW) frame, and a FSRT population
      that respectively included 23, 32, and 15 patients immobilized using Gill-Thomas
      Cosman (GTC) frame, Uniframe, and Orfit. All HF-SRT and FSRT patients were
      treated using intensity-modulated radiation therapy on a linear accelerator
      equipped with cone-beam CT (CBCT) and a robotic couch. SRS patients were treated
      using gantry-mounted stereotactic cones. The CBCT image-guidance protocol
      included initial setup, pretreatment and post-treatment verification images. The
      residual error determined from the post-treatment CBCT was used as a surrogate
      for intrafractional head motion during treatment. RESULTS: The mean
      intrafractional motion over all fractions with PinPoint was 0.62 +/- 0.33 mm and
      0.45 +/- 0.33 mm, respectively, for the HF-SRT and SRS cohort of patients (P
      value = 0.266). For CRW, GTC, Orfit, and Uniframe, the mean intrafractional
      motions were 0.30 +/- 0.21 mm, 0.54 +/- 0.76 mm, 0.73 +/- 0.49 mm, and 0.76 +/-
      0.51 mm, respectively. For CRW, PinPoint, GTC, Orfit, and Uniframe,
      intrafractional motion exceeded 1.5 mm in 0%, 0%, 5%, 6%, and 8% of all fractions
      treated, respectively. CONCLUSIONS: The noninvasive PinPoint system and the
      invasive CRW frame stringently limit cranial intrafractional motion, while the
      latter provides superior immobilization. Based on the results of this study, our
      clinical practice for malignant tumors has evolved to apply an invasive CRW frame
      only for metastases in eloquent locations to minimize normal tissue exposure.

PMID- 29363283
TI  - Maintenance interventions for overweight or obesity in children: a systematic
      review and meta-analysis.
AB  - Childhood obesity is associated with significant health consequences. Although
      several intervention programmes for children result in weight loss or
      stabilization in the short-term, preventing relapse after treatment remains an
      important challenge. This systematic review summarizes the evidence about
      maintenance interventions after treatment in childhood obesity. Studies were
      identified by searching PubMed, Embase, Cochrane Library, Scopus, Web of Science,
      PsycINFO, CINAHL and SocINDEX. The primary outcome measure for this review was
      body mass index standard deviation score (BMI-Z-score). Data were pooled using
      quality effect models. Eleven studies (1,532 participants, age 2-18 years) were
      included, covering a wide range of maintenance approaches. Included studies
      varied widely in methodological quality. Pooled analysis showed that the BMI-Z
      score of maintenance intervention participants remained stable, whereas control
      participants experienced a slight increase. No differences were observed
      regarding intensity and duration of therapy. A slight preference for 'face-to
      face' versus 'on distance' interventions was shown. In summary, this review shows
      that, although there is limited quality data to recommend one maintenance
      intervention over another, continued treatment does have a stabilizing effect on
      BMI-Z-score. Considering the magnitude of the problem of childhood obesity, this
      is an important finding that highlights the need for further research on weight
      loss maintenance.

PMID- 29363284
TI  - Identification and characterization of lumpy skin disease virus isolated from
      cattle in the Republic of North Ossetia-Alania in 2015.
AB  - The first notifications of the unknown disease of cattle appeared in September
      October 2015 in North Caucasus region of Russia (Republic of North Ossetia
      Alania). The clinical signs included watery discharge from eyes, apathy, loss of
      appetite, salivation, lameness and nodular skin lesions. Capripoxvirus genome was
      detected by real-time PCR in the tissue samples of sick animals. The aetiological
      agent was isolated in the primary cell cultures of lamb testis and goat testis,
      as well as in the continuous MDBK cell culture. Further sequencing of the GPCR
      gene and phylogenetic analysis showed the close genetic relationship of isolated
      capripoxvirus with a group of lumpy skin disease virus. Koch's postulates were
      fulfilled by the experimental infection of four calves with a suspension of
      tissue samples from sick animals.

PMID- 29363285
TI  - Modelling the variation in skin-test tuberculin reactions, post-mortem lesion
      counts and case pathology in tuberculosis-exposed cattle: Effects of animal
      characteristics, histories and co-infection.
AB  - Correctly identifying bovine tuberculosis (bTB) in cattle remains a significant
      problem in endemic countries. We hypothesized that animal characteristics (sex,
      age, breed), histories (herd effects, testing, movement) and potential exposure
      to other pathogens (co-infection; BVDV, liver fluke and Mycobacterium avium
      reactors) could significantly impact the immune responsiveness detected at skin
      testing and the variation in post-mortem pathology (confirmation) in bTB-exposed
      cattle. Three model suites were developed using a retrospective observational
      data set of 5,698 cattle culled during herd breakdowns in Northern Ireland. A
      linear regression model suggested that antemortem tuberculin reaction size
      (difference in purified protein derivative avium [PPDa] and bovine [PPDb]
      reactions) was significantly positively associated with post-mortem maximum
      lesion size and the number of lesions found. This indicated that reaction size
      could be considered a predictor of both the extent (number of lesions/tissues)
      and the pathological progression of infection (maximum lesion size). Tuberculin
      reaction size was related to age class, and younger animals (<2.85 years)
      displayed larger reaction sizes than older animals. Tuberculin reaction size was
      also associated with breed and animal movement and increased with the time
      between the penultimate and disclosing tests. A negative binomial random-effects
      model indicated a significant increase in lesion counts for animals with M. avium
      reactions (PPDb-PPDa < 0) relative to non-reactors (PPDb-PPDa = 0). Lesion counts
      were significantly increased in animals with previous positive severe
      interpretation skin-test results. Animals with increased movement histories,
      young animals and non-dairy breed animals also had significantly increased lesion
      counts. Animals from herds that had BVDV-positive cattle had significantly lower
      lesion counts than animals from herds without evidence of BVDV infection.
      Restricting the data set to only animals with a bTB visible lesion at slaughter
      (n = 2471), an ordinal regression model indicated that liver fluke-infected
      animals disclosed smaller lesions, relative to liver fluke-negative animals, and
      larger lesions were disclosed in animals with increased movement histories.

PMID- 29363286
TI  - Risk factors for occupational Brucella infection in veterinary personnel in
      India.
AB  - Brucellosis is an important animal and human health issue in developing
      countries. This study aimed to identify risk factors associated with occupational
      Brucella infection in veterinary personnel in India. Blood samples were collected
      from 279 veterinary personnel working in the public sector. Sera were tested with
      rose bengal plate test (RBPT), standard tube agglutination test (STAT), and IgG
      and IgM ELISAs. Information about participant demographics, risk of exposure and
      infection control practices was collected using a self-completed questionnaire.
      The outcome measure of Brucella infection was created based on a positive RBPT or
      STAT test and a positive IgG ELISA test. Binomial logistic regression analyses
      were conducted to evaluate associations between explanatory variables and the
      outcome variable. Of the 279 participants, 61 (21.9%), 67 (24.0%), 55 (19.7%) and
      150 (53.8%) were positive in RBPT, STAT, IgM and IgG ELISA, respectively.
      Compared to a trained veterinarian, veterinary pharmacists and animal handlers
      had greater odds of being test positive, suggesting that they were at greater
      risk of Brucella infection. Number of years spent working with animals was
      associated with greater odds of a person being positive for Brucella infection (p
      = .015). Counter-intuitively, those using personal protective equipment (PPE) for
      handling sick animals were found to be at greater risk, suggesting that either
      the use of PPE is inappropriate-making it ineffective-or that it is reverse
      association whereby those experiencing brucellosis symptoms start using PPE.
      Brucellosis is a common occupational zoonosis among veterinary personnel in India
      with the risk being higher in paraveterinary staff than veterinarians and in
      those who have been practicing for a longer period of time. Further
      investigations are required to clarify the effectiveness of PPE to reduce
      Brucella infection in veterinary personnel in India.

PMID- 29363287
TI  - Effect of Lorcaserin Alone and in Combination with Phentermine on Food Cravings
      After 12-Week Treatment: A Randomized Substudy.
AB  - OBJECTIVE: This study evaluated the effect of lorcaserin 10 mg twice daily (LOR
      BID), or with phentermine 15 mg once daily (LOR BID + PHEN QD) and 15 mg twice
      daily (LOR BID + PHEN BID), in conjunction with energy restriction on food
      cravings. METHODS: Two hundred and thirty-five patients without diabetes but with
      obesity or overweight and >= 1 comorbidity received LOR BID, LOR BID + PHEN QD,
      or LOR BID + PHEN BID for 12 weeks in a randomized double-blind study. The Food
      Craving Inventory (FCI) and the Control of Eating Questionnaire (COEQ) were
      administered over 12 weeks. RESULTS: The FCI total score and the subscale scores
      reduced from baseline in all groups. The least squares means (95% confidence
      intervals) for the total scores were -0.65 (-0.75 to -0.55), -0.75 (-0.84 to 
      0.65), and -0.84 (-0.95 to -0.74) in the LOR BID, LOR BID + PHEN QD, and LOR BID
      + PHEN BID groups, respectively. Cravings assessed by COEQ reduced from baseline
      in all groups. In general, the combination treatments were more effective than
      lorcaserin alone. At week 12, except for fruit juice and dairy products, general
      and specific cravings reduced in LOR BID + PHEN BID compared with LOR BID (P <
      0.05). CONCLUSIONS: Lorcaserin in combination with phentermine improves control
      of food cravings during short-term energy restriction.

PMID- 29363288
TI  - Isolation and phylogenetic analysis of porcine deltacoronavirus from pigs with
      diarrhoea in Hebei province, China.
AB  - Porcine deltacoronavirus (PDCoV) is a recently identified coronavirus in the
      genus Deltacoronavirus that can cause enteric disease with clinical signs
      including diarrhoea, vomiting, dehydration and mortality in neonatal piglets.
      Although evidence of the prevalence of PDCoV in China is accumulating, little
      published information about Chinese PDCoV isolates is available. In this study,
      we investigated the presence of PDCoV in 49 faecal/intestinal samples from
      piglets with diarrhoea on different farms in Hebei province. Five samples (10.2%)
      were positive for PDCoV, but no coinfection of PDCoV with other enteropathogens
      was observed. A PDCoV strain named HB-BD was successfully isolated from the
      intestinal contents of a diarrhoeic piglet and serially propagated in swine
      testicular (ST) cells for >40 passages. The complete genome of the HB-BD strain
      was sequenced and analysed. Genomic analysis showed that the HB-BD strain had a
      closer relationship with Chinese strains than those from other countries and was
      grouped within the Chinese PDCoV cluster. The results of this study will be
      valuable for further research of PDCoV genetic evolution and development of
      effective diagnostic reagents, assays and potential vaccines against newly
      emerged PDCoV strains.

PMID- 29363289
TI  - Clinical trials, culture and language: More than meets the eye?

PMID- 29363290
TI  - Brief Report: Cancer Immunotherapy in Patients With Preexisting Rheumatic
      Disease: The Mayo Clinic Experience.
AB  - OBJECTIVE: To determine the risk of rheumatic disease flare and adverse effects
      in patients with preexisting rheumatic disease who were receiving immune
      checkpoint inhibitor (ICI) therapy. METHODS: A retrospective medical record
      review was performed to identify all patients who received ICI therapy at Mayo
      Clinic in Rochester, Minnesota between 2011 and 2016 (~700 patients). Those with
      a preexisting rheumatic disease were identified using specific diagnostic codes.
      RESULTS: Sixteen patients were identified (81% female, median age 68.5 years).
      The most common rheumatic diseases were rheumatoid arthritis (n = 5), polymyalgia
      rheumatica (n = 5), Sjogren's syndrome (n = 2), and systemic lupus erythematosus
      (n = 2). Seven patients were receiving immunosuppressive therapy or
      glucocorticoids for their rheumatic disease at the time of initiation of the ICI.
      The primary malignancies were melanoma (n = 10), pulmonary (n = 4), or
      hematologic (n = 2). In most cases, ICIs were offered only after failure of
      several other therapies. Immune-related adverse effects (IRAEs) occurred in 6
      patients, and all were treated successfully with glucocorticoids and
      discontinuation of the ICI therapy. There were no significant differences in time
      from cancer diagnosis to immunotherapy, duration of immunotherapy, age, or sex
      between the patients with and those without IRAEs. CONCLUSION: To our knowledge,
      this represents the largest single-center cohort of patients with rheumatic
      diseases who were exposed to modern cancer immunotherapy. Only a minority of
      these patients experienced a flare of their preexisting rheumatic disease or any
      other IRAE.

PMID- 29363291
TI  - Flexible nine-channel photodetector probe facilitated intraspinal multisite
      transcutaneous photobiomodulation therapy dosimetry in cadaver dogs.
AB  - Noninvasive photobiomodulation therapy (PBMT) of spinal cord disease remains
      speculative due to the lack of evidence for whether photobiomodulatory
      irradiances can be transcutaneously delivered to the spinal cord under a
      clinically acceptable PBMT surface irradiation protocol. We developed a flexible
      nine-channel photodetection probe for deployment within the spinal canal of a
      cadaver dog after hemilaminectomy to measure transcutaneously transmitted PBMT
      irradiance at nine sites over an eight-cm spinal canal length. The probe was
      built upon a 6.325-mm tubular stem, to the surface of which nine photodiodes were
      epoxied at approximately 1 cm apart. The photodiode has a form factor of 4.80 
      mm*2.10  mm*1.15  mm (length*width*height). Each photodiode was individually
      calibrated to deliver 1 V per 7.58  MUW/cm2 continuous irradiance at 850 nm. The
      outputs of eight photodiodes were logged concurrently using a data acquisition
      module interfacing eight channels of differential analog signals, while the
      output of the ninth photodiode was measured by a precision multimeter. This
      flexible probe rendered simultaneous intraspinal (nine-site) measurements of
      transcutaneous PBMT irradiations at 980 nm in a pilot cadaver dog model. At a
      surface continuous irradiance of 3.14  W/cm2 applied off-contact between L1 and
      L2, intraspinal irradiances picked up by nine photodiodes had a maximum of 327.48
      MUW/cm2 without the skin and 5.68  MUW/cm2 with the skin.

PMID- 29363292
TI  - Acute intoxications among Turkish children.
AB  - BACKGROUND: The aim of this study was to investigate characteristics, outcomes
      and clinical features of acute intoxications among children in Van region of
      Turkey. METHODS: All cases with a diagnosis of acute intoxication admitted to the
      Pediatric Emergency Department of the Yuzuncu Yil University of Van from June 1,
      2010 to November 30, 2011 were evaluated. We retrospectively examined the medical
      records for demographical and etiological characteristics of patients below 17
      years of age. RESULTS: A total of 239 intoxications were recorded. The majority
      of patients were under 5 years of age. Pharmaceutical agents were identified in
      137 (57.3%) patients. Antidepressants with a majority of tricyclic
      antidepressants were the most common drugs (29.9%). Non-pharmaceutical agents
      were identified in 102 (42.6%) patients, 38.2% of which were insecticides
      pesticides following by plants (25.4%) and carbon monoxide (17.6%). The majority
      (93.8%) of cases were accidental poisonings. Fourteen cases of intoxications
      occurred as suicide attempts and 85.7% (N.=12) of those patients were girls. Of
      all cases, gastric lavage was performed in 36.4% and activated charcoal
      administration in 53%. After hospitalization, only 23 (9.6%) of all patients
      received specific treatment besides symptomatic treatment. Specific treatments
      involved hemodialysis and antidotes such as biperiden, ethanol, atropine,
      neostigmine and pralidoxime. During the study period, one patient died due to
      acute intoxication of pesticide. The mortality rate was 0.4%. CONCLUSIONS: Our
      study revealed that pharmaceuticals were the most common cause of acute
      intoxications. While, insecticides-pesticides and plants were the leading non
      pharmaceutic agents. Our data is important because it is one of few original
      reports on children with intoxication in Eastern Turkey.

PMID- 29363294
TI  - Autism: the solar rainbow spectrum.

PMID- 29363293
TI  - Safety of HPV vaccines in the age of nonavalent vaccination.
AB  - To date three vaccines against human papilloma virus (HPV) have been licensed: a
      bivalent, a quadrivalent and, in 2014, a nonavalent vaccine. Despite the early
      implementation of national vaccination programs, in the majority of developed
      countries coverage rates remain unsatisfactory. Rumors about vaccine safety have
      been one of the principal obstacles for the acceptance of HPV vaccination by the
      public. It is therefore of primary importance to provide the public with clear
      and up-to-date information about HPV vaccination safety. To this aim, in this
      narrative review we will summarize safety data from pre and postlicensure studies
      for the three HPV vaccines available with a focus on the safety profile of the
      new nonavalent vaccine.

PMID- 29363295
TI  - Successful intraosseous therapy using EZ-IO system in a preterm neonate below 2
      kg.

PMID- 29363296
TI  - Seizures in preterm newborns.

PMID- 29363297
TI  - Teratogenicity of systemic isotretinoin.

PMID- 29363298
TI  - Long-term survival after glioblastoma resection: hope despite poor prognosis
      factors.
AB  - BACKGROUND: In spite of aggressive multimodal treatment, survival for patients
      with glioblastoma (GBM) remains short. Nevertheless, some patients survive much
      longer than expected and become long- term survival patients. The extent of
      resection (EoR), Karnofsky Performance Scale (KPS), age and methyl-guanine
      methyltransferase gene (MGMT) methylation are well-defined prognostic factors,
      but the characteristics of patients with long-term survival (LTS, survival of at
      least three years after diagnosis) has not been fully determined yet. That is the
      reason why we analyzed the GBM patients with LTS at our center. METHODS: We
      retrospectively reviewed all consecutive patients who underwent surgery for GBM
      between January 2002 and November 2011, including patients treated with surgical
      resection under neuronavigation with or without intraoperative MRI (ioMRI) and
      those who had stereotactic biopsy. We identified and further analysed those
      patients with LTS. RESULTS: A total of 127 patients underwent surgery for GBM
      during the study period. 101 (79.6%) of whom had surgical resection and 26
      (20.4%) of whom had stereotactic biopsy. Of the 101 patients who were treated
      with surgical resection, 12 had LTS. After two other pathologists reviewed the
      patients' cases, they confirmed that 11 (11%) of the 12 patients had a GBM
      (female/male ratio 4.5; average age 50 years; pre-op Karnofsky score 82%), and
      one patient had an anaplastic glioma. The mean survival in the LTS patients with
      confirmed GBM was 74 (36-150) months. Seven of the LTS patients (63.6%) had a
      gross total resection (GTR), including two with an additional resection after
      ioMRI. Three (27.3%) had a near total resection (NTR: residue <= 5%) and one
      (9.1%) had a partial resection. Ten (90.9%) patients had a methylation of MGMT,
      only two (18.8%) had an IDH1 mutation, and seven (63.6%) received a full Stupp
      protocol. CONCLUSION: Among patients with a GBM who were treated with one or more
      resections, 11% had LTS with 90.9% with at least a near total resection (36% with
      ioMRI) and a methylated MGMT. 50% of the patients with a second surgery survived
      at least two years postoperatively. Those encouraging observations emphasize the
      importance of maximizing the resection by using, if possible, an intraoperative
      guidance method like ioMRI with an analysis of biomarkers such as MGMT and if
      necessary, multiple surgical procedures.

PMID- 29363299
TI  - Thoracic and lumbosacral spinal giant schwannoma.

PMID- 29363300
TI  - Full Characterization of CO2-Oil Properties On-Chip: Solubility, Diffusivity,
      Extraction Pressure, Miscibility, and Contact Angle.
AB  - Carbon capture, storage, and utilization technologies target a reduction in net
      CO2 emissions to mitigate greenhouse gas effects. The largest such projects
      worldwide involve storing CO2 through enhanced oil recovery-a technologically and
      economically feasible approach that combines both storage and oil recovery.
      Successful implementation relies on detailed measurements of CO2-oil properties
      at relevant reservoir conditions (P = 2.0-13.0 MPa and T = 23 and 50  degrees C).
      In this paper, we demonstrate a microfluidic method to quantify the comprehensive
      suite of mutual properties of a CO2 and crude oil mixture including solubility,
      diffusivity, extraction pressure, minimum miscibility pressure (MMP), and contact
      angle. The time-lapse oil swelling/extraction in response to CO2 exposure under
      stepwise increasing pressure was quantified via fluorescence microscopy, using
      the inherent fluorescence property of the oil. The CO2 solubilities and diffusion
      coefficients were determined from the swelling process with measurements in
      strong agreement with previous results. The CO2-oil MMP was determined from the
      subsequent oil extraction process with measurements within 5% of previous values.
      In addition, the oil-CO2-silicon contact angle was measured throughout the
      process, with contact angle increasing with pressure. In contrast with
      conventional methods, which require days and ~500 mL of fluid sample, the
      approach here provides a comprehensive suite of measurements, 100-fold faster
      with less than 1 MUL of sample, and an opportunity to better inform large-scale
      CO2 projects.

PMID- 29363301
TI  - Incorporating Trialkylsilylethynyl-Substituted Head-to-Head Bithiophene Unit into
      Copolymers for Efficient Non-Fullerene Organic Solar Cells.
AB  - Mediating the backbone coplanarity and solubility of oligothiophenes, especially
      the head-to-head (HH) disubstituted bithiophene, to achieve an optically and
      electronically advantageous building block for organic semiconductor materials is
      a vital yet challenging task. On the other hand, exploring polymer solar cells
      (PSCs) processed from nonhalogenated solvents is necessary toward their large
      scale applications. In this contribution, we develop a HH-type bithiophene
      analogue (TIPS-T2) by strategically applying the triisopropylsilylethynyl (TIPS)
      scaffold as the side chain. TIPS can serve to narrow optical band gaps, lower the
      highest occupied molecular orbital level, reduce intrachain steric hindrance, and
      guarantee sufficient solubility of the involving polymers. Upon alternating with
      difluorobenzotriazole (FTAZ) or benzodithiophene-4,8-dione (BDD) acceptor units,
      two polymers named PT4Si-FTAZ and PT4Si-BDD are synthesized. Encouragingly, non
      fullerene PSCs incorporating PT4Si-FTAZ yield a power conversion efficiency of
      6.79% when processed from an environment-friendly solvent of trimethylbenzene
      because of its promoted backbone planarity, as demonstrated by density functional
      theory, higher hole mobility, and superior film morphology. The results indicate
      that TIPS-T2 is a promising building block for constructing photovoltaic
      polymers, and our findings offer an avenue for the ingenious use of TIPS as
      functional side chains.

PMID- 29363302
TI  - Highly Exfoliated MWNT-rGO Ink-Wrapped Polyurethane Foam for Piezoresistive
      Pressure Sensor Applications.
AB  - The fabrication of pressure sensors based on reduced graphene oxide (rGO) as the
      sensing material is challenging due to the intrinsic hydrophobic behavior of
      graphene oxide inks as well as the agglomeration of graphene oxide flakes after
      reduction. Hydrazine (a reducing agent) and a dual-component additive comprising
      benzisothiazolinone and methylisothiazolinone in appropriate proportion were used
      to synthesize a rGO ink with a hydrophilic nature. Utilizing this hydrophilic rGO
      ink mixed with multiwalled carbon nanotubes (MWNTs), a very simple, low-cost
      approach is demonstrated for the fabrication of a pressure sensor based on
      polyurethane (PU) foam coated with the MWNT-rGO ink (MWNT-rGO@PU foam). The MWNT
      rGO@PU foam-based devices are shown to be versatile pressure sensors with the
      potential to detect both small-scale and large-scale movements. At low pressure
      (below 2.7 kPa, 50% strain), the formation of microcracks that scatter electrical
      charges results in a detectable increase in resistance suitable for detecting
      small-scale motion. At a higher pressure, the compressive contact of the coated
      faces of the PU foam results in a sharp decrease in resistance suitable for
      monitoring of large-scale motion. Moreover, these sensors exhibit good
      flexibility and reproducibility over 5000 cycles. The versatility of this sensor
      has been demonstrated in a wide range of applications, such as speech
      recognition, health monitoring, and body motion detection. The significant
      advantages of this sensor are that its cost is low, it is easy to fabricate, and
      it has a versatility that renders it favorable to health-monitoring applications.

PMID- 29363303
TI  - Rapidly Responsive and Flexible Chiral Nematic Cellulose Nanocrystal Composites
      as Multifunctional Rewritable Photonic Papers with Eco-Friendly Inks.
AB  - Rapidly responsive and flexible photonic papers are manufactured by coassembly of
      cellulose nanocrystals (CNCs) and waterborne polyurethane (WPU) latex for fully
      taking advantage of the chiral nematic structure of CNCs and the flexibility of
      WPU elastomer. The resulting CNC/WPU composite papers exhibit not only tunable
      iridescent colors by adjusting the helical pitch size, but also instant optical
      responses to water and wet gas, ascribed to the easy chain movement of the
      elastomeric WPU that does not restrict the fast water absorption-induced swelling
      of CNCs. By choosing water or NaCl aqueous solutions as inks, the colorful
      patterns on the CNC/WPU photonic paper can be made temporary, durable, or even
      disguisable. In addition, the photonic paper is simultaneously rewritable for all
      these three types of patterns, and the disguisable patterns, which are invisible
      at normal times and show up under stimuli, exhibit a quick reveal conversion just
      by exhaling on the paper. The rewritability, rapid responsibility, easy
      fabrication, and the eco-friendly nature of the inks make the flexible photonic
      paper/ink combination highly promising in sensors, displays, and photonic
      circuits.

PMID- 29363304
TI  - Real-Time Visualization of Cysteine Metabolism in Living Cells with Ratiometric
      Fluorescence Probes.
AB  - Sulfite from cysteine metabolism in living cells plays a crucial role in
      improving the water solubility of metabolic xenobiotics for their easier
      excretion in urine or bile. However, an imbalance of sulfite in vivo would lead
      to oxidative stress or age-related diseases, and an effective strategy for real
      time imaging of cysteine metabolism in living cells is still lacking due to its
      low metabolite concentration and rapid reaction kinetics. Herein, a cyanine
      moiety based ratiometric fluorescence probe was developed for highly selective
      and sensitive detection of sulfite in aqueous solution and living cells. The free
      probe exhibited an orange emission color, and the fluorescence color would
      gradually change to blue once sulfite anions selectively reacted with the
      unsaturated carbon double bonds in the probe molecule. This ratiometric
      fluorescence manner endowed the probe excellent sensitivity with a detection
      limit of 0.78 nM, which was then explored to image the kinetic process of sulfite
      release in hepatic BRL cells after incubating with an excess amount of cysteine.
      This strategy opens new opportunities for revealing thiol-containing species
      metabolism and even quantitatively tracking their distributions in live cells or
      organelles.

PMID- 29363305
TI  - Fecal Metabolomics of Type 2 Diabetic Rats and Treatment with Gardenia
      jasminoides Ellis Based on Mass Spectrometry Technique.
AB  - Modern studies have indicated Gardenia jasminoides Ellis (G. jasminoides) showed
      positive effect in treating type 2 diabetes mellitus (T2DM). In this study, 60
      streptozotocin-induced T2DM rats were divided into four groups: type 2 diabetes
      control group, geniposide-treated group, total iridoid glycosides-treated group,
      and crude extraction of gardenlae fructus-treated group. The other ten healthy
      rats were the healthy control group. During 12 weeks of treatment, rat's feces
      samples were collected for the metabolomics study based on mass spectrometry
      technique. On the basis of the fecal metabolomics method, 19 potential biomarkers
      were screened and their relative intensities in each group were compared. The
      results revealed G. jasminoides mainly regulated dysfunctions in phenylalanine
      metabolism, tryptophan metabolism, and secondary bile acid biosynthesis pathways
      induced by diabetes. The current study provides new insight for metabonomics
      methodology toward T2DM, and the results show that feces can preferably reflect
      the liver and intestines disorders.

PMID- 29363306
TI  - Product Studies and Mechanistic Analysis of the Reaction of Methylglyoxal with
      Deoxyguanosine.
AB  - Methylglyoxal (MG) is a highly reactive electrophile produced endogenously as a
      byproduct of glucose metabolism and protein catabolism and exogenously as a food
      contaminant. MG reacts spontaneously with proteins, lipids, and nucleic acids to
      form advanced glycation end products (AGEs), modifying or inhibiting their
      function. Protein AGEs are associated with pathological complications of
      diabetes, cancer, and neurodegenerative diseases, while the physiological impact
      of DNA, RNA, and lipid AGE formation is less well explored. Conflicting reports
      in the literature on the biologically significant DNA-AGE product distribution
      and mechanisms of formation prompted a re-examination of the reaction products of
      MG with dG, oligonucleotides, and plasmid DNA under varying conditions of MG:dG
      stoichiometry, pH, and reaction time. Major products identified using sequential
      mass fragmentation and authentic standards were N2-(1-carboxyethyl)-2'-dG (CEdG),
      N2-(1-carboxyethyl)-7-1-hydroxy-2-oxopropyl-dG (MG-CEdG), and 1,N2-(1,2-dihydroxy
      2-methyl)ethano-2'-dG (cMG-dG). CEdG and MG-CEdG were observed in all DNA
      substrates, although cMG-dG was not detected to any significant extent in
      oligomeric or polymeric DNA. Product analyses of reactions under conditions of
      diminished water activity as well as results from H218O labeling indicated that
      MG hydration equilibria plays an important role in controlling product
      distribution. In contrast to previous reports, our data support independent
      mechanisms of formation of CEdG and cMG-dG, with the latter kinetic product
      undergoing reversible formation under physiological conditions.

PMID- 29363307
TI  - Photothermal Nanocomposite Hydrogel Actuator with Electric-Field-Induced Gradient
      and Oriented Structure.
AB  - Recent research of hydrogel actuators is still not sophisticated enough to meet
      the requirement of fast, reversible, complex, and robust reconfiguration. Here,
      we present a new kind of poly( N-isopropylacrylamide)/graphene oxide gradient
      hydrogel by utilizing direct current electric field to induce gradient and
      oriented distribution of graphene oxide into poly( N-isopropylacrylamide)
      hydrogel. Upon near-infrared light irradiation, the hydrogel exhibited excellent
      comprehensive actuation performance as a result of directional bending
      deformation, promising great potential in the application of soft actuators and
      optomechanical system.

PMID- 29363308
TI  - Supercritical Fluids for Higher Extraction Yields of Lipids from Archeological
      Ceramics.
AB  - The extraction and study of organic residues from ceramics has been a subject of
      interest for the last 50 years in archeology and archeological science. Lipids
      are among the best-preserved organic substances in archeological contexts and can
      provide information about the diets of ancient populations as well as past
      environments. Here, we present a method which demonstrates significantly improved
      extraction of lipids from archeological pots by replacing liquid organic solvents
      with supercritical fluids. Optimization of the procedure using response surface
      methodology (RSM) approach showed that, on our system, optimal conditions for
      supercritical extraction of lipids from synthetic fired clay ceramics could be
      achieved using carbon dioxide with 16 vol % of cosolvent EtOH-H2O (95:5 v/v) in
      90 min at a flow rate of 2.3 mL/min, for a pressure of 30 MPa and a temperature
      of 50  degrees C. For all reference and archeological samples included in this
      study, lipid yields obtained by supercritical fluid extraction under these
      optimal conditions were systematically higher than by conventional solvent
      extraction. This study also highlighted a variability of the ratio of unsaturated
      versus saturated fatty acids depending on the extraction method. This can have
      important implications in the identification of the residue(s). The increased
      extraction efficiency provided by supercritical fluids, as well as their
      minimally destructive nature, enable new and refined approaches to residue
      analysis and dating of archeological ceramics.

PMID- 29363309
TI  - Ab Initio Study on Surface Segregation and Anisotropy of Ni-Rich LiNi1-2yCoyMnyO2
      (NCM) (y <= 0.1) Cathodes.
AB  - Advances in ex situ and in situ (operando) characteristic techniques have
      unraveled unprecedented atomic details in the electrochemical reaction of Li-ion
      batteries. To bridge the gap between emerging evidences and practical material
      development, an elaborate understanding on the electrochemical properties of
      cathode materials on the atomic scale is urgently needed. In this work, we
      perform comprehensive first-principle calculations within the density functional
      theory + U framework on the surface stability, morphology, and elastic anisotropy
      of Ni-rich LiNi1-2yCoyMnyO2 (NCM) (y <= 0.1) cathode materials, which are
      strongly related to the emerging evidence in the degradation of Li-ion batteries.
      On the basis of the surface stability results, the equilibrium particle
      morphology is obtained, which is mainly determined by the oxygen chemical
      potential. Ni-rich NCM particles are terminated mostly by the (012) and (001)
      surfaces for oxygen-poor conditions, whereas the termination corresponds to the
      (104) and (001) surfaces for oxygen-rich conditions. Besides, Ni surface
      segregation predominantly occurs on the (100), (110), and (104) nonpolar
      surfaces, showing a tendency to form a rocksalt NiO domain on the surface because
      of severe Li-Ni exchange. The observed elastic anisotropy reveals that an uneven
      deformation is more likely to be formed in the particles synthesized under poor
      oxygen conditions, leading to crack generation and propagation. Our findings
      provide a deep understanding of the surface properties and degradation of Ni-rich
      NCM particles, thereby proposing possible solution mechanisms to the factors
      affecting degradation, such as synthesis conditions, coating, or novel
      nanostructures.

PMID- 29363310
TI  - Preparation of 4-Deoxy-L-erythro-5-hexoseulose Uronic Acid (DEH) and Guluronic
      Acid Rich Alginate Using a Unique exo-Alginate Lyase from Thalassotalea
      crassostreae.
AB  - Marine multicellular algae are considered promising crops for the production of
      sustainable biofuels and commodity chemicals. However, their commercial
      exploitation is currently limited by a lack of appropriate and efficient enzymes
      for converting alginate into metabolizable building blocks, such as 4-deoxy-L
      erythro-5-hexoseulose uronic acid (DEH). Herein, we report the discovery and
      characterization of a unique exo-alginate lyase from the marine bacterium
      Thalassotalea crassostreae that possesses excellent catalytic efficiency against
      poly-beta-D-mannuronate (poly M) alginate, with a kcat of 135.8 s-1, and a 5-fold
      lower kcat of 25 s-1 against poly-alpha-L-guluronate (poly G alginate). We
      propose that this preference for poly M is due to a structural feature of the
      protein's active site. The mode of action and specificity of this enzyme has made
      it possible to design an effective and environmentally friendly process for the
      production of DEH and low molecular weight guluronate-enriched alginate.

PMID- 29363311
TI  - Label-Free Sensing of Human 8-Oxoguanine DNA Glycosylase Activity with a
      Nanopore.
AB  - Human 8-oxoguanine DNA glycosylase (hOGG1) plays a significant role in
      maintaining the genomic integrity of living organisms for its capability of
      repairing DNA lesions. Accurate detection of hOGG1 activity would greatly
      facilitate the screening and early diagnosis of diseases. In this work, we report
      a nanopore-based sensing strategy to probe the hOGG1 activity by employing the
      enzyme-catalytic cleavage reaction of DNA substrate. The hOGG1 specifically
      catalyzed the removal of the 8-hydroxyguanine (8-oxoG) and cleaved the DNA
      substrates immobilized on magnetic beads, thereby releasing the output DNA which
      would quantitatively produce the signature current events when subjected to alpha
      hemolysin (alpha-HL) nanopore test. The approach enables the sensitive detection
      of hOGG1 activity without the need of any labeling or signal amplification route.
      Furthermore, the method can be applied to assay the inhibition of hOGG1 and
      evaluate the activity of endogenous hOGG1 in crude cell extracts. Importantly,
      since DNAs with specific sequences are the catalytic substrates of a wide variety
      of enzymes, the proposed strategy should be universally applicable for probing
      the activities of different types of enzymes with nanopore sensors.

PMID- 29363312
TI  - Mobility of Aqueous and Colloidal Neptunium Species in Field Lysimeter
      Experiments.
AB  - Due to its radiotoxicity, long half-life, and potentially high environmental
      mobility, neptunium transport is of paramount importance for risk assessment and
      safety. Environmental transport of neptunium through field lysimeters at the
      Savannah River Site was observed from both oxidized (Np(V)) and reduced (Np(IV))
      source materials. While transport from oxidized neptunium sources was expected,
      the unexpected transport from reduced neptunium sources spurred further
      investigation into transport mechanisms. Partial oxidation of the reduced
      neptunium source resulted in significant release and transport into the mobile
      aqueous phase, though a reduced colloidal neptunium species appears to have also
      been present, enhancing neptunium mobility over shorter distances. These field
      and laboratory experiments demonstrate the multiple controls on neptunium vadose
      zone transport and chemical behavior, as well as the need for thorough
      understanding of radionuclide source terms for long-term risk prediction.

PMID- 29363313
TI  - Biomimetic Mineralization Guided One-Pot Preparation of Gold Clusters Anchored
      Two-Dimensional MnO2 Nanosheets for Fluorometric/Magnetic Bimodal Sensing.
AB  - A novel fluorometric/magnetic bimodal sensor is reported based on gold
      nanoclusters (Au NCs)-anchored two-dimensional (2D) MnO2 nanosheets (Au NCs-MnO2)
      that are synthesized through a one-pot biomimetic mineralization process. Bovine
      serum albumin (BSA) was used as the template to guide the formation and assembly
      of the Au NCs-MnO2 under physiological conditions and without use of any strong
      oxidizing agent and toxic surfactants as well as organic solvent. The
      fluorescence of Au NCs was first quenched by MnO2 nanosheets, while upon H2O2
      introduction, the MnO2 nanosheets can be sensitively and selectively reduced to
      Mn2+ with enhanced magnetic resonance (MR) signal and rapid recovery of Au NCs
      fluorescence simultaneously. This dual-modal strategy can overcome the weakness
      of a single-fluorescence detection mode. A linear range of 0.06-2 MUM toward H2O2
      was obtained for the fluorescence mode, whereas the MR mode also allowed
      detection of H2O2 at a concentration that ranged from 0.01 to 0.2 mM. Benefiting
      from the BSA molecule residual on the product surface, the as-prepared Au NCs
      MnO2 displays low cytotoxicity and good biocompatibility. Importantly, the
      successful application of Au NCs-MnO2 for analysis of H2O2 in biological samples
      and cells indicates that the integration of Au NCs fluorescence with Mn2+ MR
      response provides a promising bimodal sensing platform for H2O2 in vivo
      monitoring.

PMID- 29363315
TI  - Real-Space Observation of Skyrmionium in a Ferromagnet-Magnetic Topological
      Insulator Heterostructure.
AB  - The combination of topological insulators, that is, bulk insulators with gapless,
      topologically protected surface states, with magnetic order is a love-hate
      relationship that can unlock new quantum states and exotic physical phenomena,
      such as the quantum anomalous Hall effect and axion electrodynamics. Moreover,
      the unusual coupling between topological insulators and ferromagnets can also
      result in the formation of topological spin textures in the ferromagnetic layer.
      Skyrmions are topologically protected magnetization swirls that are promising
      candidates for spintronics memory carriers. Here, we report on the observation of
      skyrmionium in thin ferromagnetic films coupled to a magnetic topological
      insulator. The occurrence of skyrmionium, which appears as a soliton composed of
      two skyrmions with opposite winding numbers, is tied to the ferromagnetic state
      of the topological insulator. Our work presents a new combination of two
      important classes of topological materials and may open the door to new
      topologically inspired information-storage concepts in the future.

PMID- 29363316
TI  - Target Confinement in Small Reaction Volumes Using Microfluidic Technologies: A
      Smart Approach for Single-Entity Detection and Analysis.
AB  - Over the last decades, the study of cells, nucleic acid molecules, and proteins
      has evolved from ensemble measurements to so-called single-entity studies. The
      latter offers huge benefits, not only as biological research tools to examine
      heterogeneities among individual entities within a population, but also as
      biosensing tools for medical diagnostics, which can reach the ultimate
      sensitivity by detecting single targets. Whereas various techniques for single
      entity detection have been reported, this review focuses on microfluidic systems
      that physically confine single targets in small reaction volumes. We categorize
      these techniques as droplet-, microchamber-, and nanostructure-based and provide
      an overview of their implementation for studying single cells, nucleic acids, and
      proteins. We furthermore reflect on the advantages and limitations of these
      techniques and highlight future opportunities in the field.

PMID- 29363317
TI  - In-situ left-sided bilateral internal thoracic artery: elevated hemidiaphragm.
AB  - Background Procurement of the internal thoracic artery risks ipsilateral phrenic
      nerve injury and elevated hemidiaphragm. Anatomical variations increase the risk
      on the right side. Patients receiving left-sided in-situ right internal thoracic
      artery configurations appear to be at greatest risk. Methods From 2014 to 2016,
      432 patients undergoing left-sided in-situ bilateral internal thoracic artery
      grafting were grouped according to right internal thoracic artery configuration:
      retroaortic via transverse sinus (77%) or ante-aortic (23%); targets were the
      circumflex and left anterior descending artery territories, respectively.
      Elevated hemidiaphragm was assessed by serial chest radiographs and categorized
      by side, complete (>=2 intercostal spaces) versus partial, and permanent versus
      transient. Results Right elevated hemidiaphragm occurred in 4.2% of patients. The
      incidence of radiological complete right elevated hemidiaphragm was 2.8%
      (12/432); 8 cases were transient with recovery in 3.5 +/- 0.3 weeks. Permanent
      right elevated hemidiaphragm occurred in 0.9% (retroaortic group only). Permanent
      left elevated hemidiaphragm occurred in 0.9% and was significantly higher in the
      ante-aortic group (3/99 vs. 1/333, p = 0.039). No bilateral hemidiaphragm
      elevation was documented. Partial right elevated hemidiaphragm occurred in 1.4%
      and was not associated with adverse early or late respiratory outcomes.
      Conclusions Despite susceptible right phrenic nerve-internal thoracic artery
      anatomy, the incidence of permanent right elevated hemidiaphragm is low and no
      higher than left-sided in prone bilateral internal thoracic artery subsets. This
      reflects skeletonized internal thoracic artery procurement. Although statistical
      significance was not achieved, a retroaortic right internal thoracic artery
      configuration may constitute a higher risk of right phrenic nerve injury.

PMID- 29363318
TI  - Characterization of single vs. recurrent spontaneous coronary artery dissection.
AB  - Background Spontaneous coronary artery dissection is a rare non-atherosclerotic
      cause of acute coronary syndromes, often underdiagnosed based on standard
      coronary angiography. Moreover, features, presentation, and intravascular imaging
      of recurrent spontaneous dissections have not been assessed. Methods Patients
      with recurrent spontaneous coronary artery dissection, who were admitted to our
      catheterization laboratory over a 10-year period, were identified. Demographic,
      clinical, angiographic, and intravascular imaging data were reviewed and
      analyzed, comparing patients with a single event with those who had a recurrence.
      Results Over the study period, 31 (0.2%, mean age 48.1 +/- 8.8 years, 24 females)
      of 10,954 patients who underwent coronary angiography experienced a single
      spontaneous coronary artery dissection, and 6 (0.05%, mean age 49.3 +/- 10.1
      years, 4 females) experienced recurrent spontaneous coronary artery dissection.
      No patient suffered more than 2 dissections. Arterial hypertension ( p = 0.004),
      a string sign measuring >15 mm on angiography, and hematoma on intravascular
      ultrasound imaging were more frequently observed in patients with recurrent
      spontaneous coronary artery dissection. Conclusions Hypertension, length of the
      string sign on angiography, and hematoma on intravascular ultrasound imaging
      might identify patients at higher risk of recurrent spontaneous coronary artery
      dissection despite a lifelong dual antiplatelet regimen.

PMID- 29363314
TI  - Life under the Microscope: Single-Molecule Fluorescence Highlights the RNA World.
AB  - The emergence of single-molecule (SM) fluorescence techniques has opened up a
      vast new toolbox for exploring the molecular basis of life. The ability to
      monitor individual biomolecules in real time enables complex, dynamic folding
      pathways to be interrogated without the averaging effect of ensemble
      measurements. In parallel, modern biology has been revolutionized by our emerging
      understanding of the many functions of RNA. In this comprehensive review, we
      survey SM fluorescence approaches and discuss how the application of these tools
      to RNA and RNA-containing macromolecular complexes in vitro has yielded
      significant insights into the underlying biology. Topics covered include the
      three-dimensional folding landscapes of a plethora of isolated RNA molecules,
      their assembly and interactions in RNA-protein complexes, and the relation of
      these properties to their biological functions. In all of these examples, the use
      of SM fluorescence methods has revealed critical information beyond the reach of
      ensemble averages.

PMID- 29363319
TI  - Morphological analysis using geometric parameters for splenic aneurysms.
AB  - Background Considering the unique characteristics of splenic artery aneurysms, we
      hypothesized that hemodynamic forces could play an important role in splenic
      artery aneurysm formation and that splenic artery geometry should be correlated
      with aneurysm development. Methods Tortuosity of the splenic artery was evaluated
      three-dimensionally by calculating the curvature using software and the original
      modeling system. We selected 54 splenic artery aneurysm patients who had
      undergone thin-slice computed tomography imaging with contrast. We compared the
      splenic artery aneurysm group to non-vascular patients via propensity-score
      matching (35 patients in each group). The splenic artery length index, average
      curvature, and maximum curvature were analyzed. Results Splenic artery aneurysm
      patients tended to have a longer splenic artery and the curvature was more severe
      compared to the non-vascular control patients. The average curvature of splenic
      artery aneurysm patients was associated with the dilatation rate in female
      patients. Conclusion Females with a tortuous splenic artery may have an increased
      risk of aneurysm formation.

PMID- 29363320
TI  - Outcomes of lung transplant recipients with preoperative atrial fibrillation.
AB  - Background Preoperative atrial fibrillation is associated with poor outcomes
      after cardiac surgery, but its effect on lung transplantation outcomes remains
      unknown. Methods We retrospectively reviewed the charts of 235 patients who
      underwent lung transplantation in our institution from 2013 to 2015, analyzing
      demographics, length of stay, survival, readmissions, and cardiac events. Mean
      recipient age was 59 +/- 11 years, and 142 (60.4%) were men. Patients were
      grouped according to pre-transplantation atrial fibrillation status (atrial
      fibrillation/no atrial fibrillation). Results The atrial fibrillation group ( n =
      38; 16.2%) was significantly older with a longer ischemic time, more
      postoperative atrial arrhythmias (73.7% vs. 20.8%, p = 0.01), and a longer median
      postoperative length of stay (16 vs. 13 days, p = 0.02). The median total
      hospital stay in the first postoperative year was also higher in the atrial
      fibrillation group (27 vs. 21 days, p = 0.25). Short-term survival and survival
      during follow-up did not differ significantly between groups. Conclusions Lung
      transplant recipients with preoperative atrial fibrillation are at increased risk
      of adverse cardiovascular outcomes and longer hospital stay. Preoperative atrial
      fibrillation may portend adverse events after lung transplantation.

PMID- 29363322
TI  - Albuminuria in kidney transplant recipients is associated with increased urinary
      serine proteases and activation of the epithelial sodium channel.
AB  - Albuminuria predicts adverse renal outcome in kidney transplant recipients. The
      present study addressed the hypothesis that albuminuria is associated with
      increased urine serine proteases with the ability to activate the epithelial
      sodium channel (ENaC) and with greater extracellular volume and higher blood
      pressure. In a cross-sectional design, kidney transplant recipients with ( n =
      18) and without ( n = 19) albuminuria were included for office blood pressure
      measurements, estimation of volume status by bioimpedance, and collection of spot
      urine and plasma samples. Urine was analyzed for serine proteases and for the
      ability to activate ENaC current in vitro. Urine exosome protein was
      immunoblotted for prostasin and gamma-ENaC protein. In the present study, it was
      found that, compared with nonalbuminuria (8.8 mg/g creatinine), albuminuric
      (1,722 mg/g creatinine) kidney transplant recipients had a higher systolic and
      diastolic blood pressure, despite receiving significantly more antihypertensives,
      and a greater urinary total plasminogen, active plasmin, active urokinase-type
      plasminogen activator, and prostasin protein abundance, which correlated
      significantly with u-albumin. Fluid overload correlated with systolic blood
      pressure, urinary albumin/creatinine, and plasminogen/creatinine. Urine from
      albuminuric kidney transplant recipients evoked a greater amiloride- and
      aprotinin-sensitive inward current in single collecting duct cells (murine cell
      line M1). gammaENaC subunits at 50 and 75 kDa showed increased abundance in urine
      exosomes from albuminuric kidney transplant recipients when compared with
      controls. These findings show that albuminuria in kidney transplant recipients is
      associated with hypertension, ability of urine to proteolytically activate ENaC
      current, and increased abundance of gammaENaC. ENaC activity could contribute to
      hypertension and adverse outcome in posttransplant proteinuria.

PMID- 29363321
TI  - Comparison of contrast-enhanced ultrasound with MRI in the diagnosis of complex
      cystic renal masses: a meta-analysis.
AB  - Background The differential diagnosis of cystic renal masses still faces great
      challenges. There has been no systematically assessment to compare the value of
      contrast-enhanced ultrasound (CEUS) with magnetic resonance imaging (MRI) in the
      diagnosis of cystic renal masses. Purpose To perform a meta-analysis to compare
      the diagnostic efficacy of CEUS with that of MRI for cystic renal masses.
      Material and Methods A systematic search was performed for literature evaluating
      the diagnostic performance of CEUS or MRI in cystic renal masses. Quality
      assessment of diagnostic studies 2 (QUADAS-2) was used to evaluate the quality of
      each study included. The pooled sensitivity, specificity, positive likelihood
      ratio, negative likelihood ratio, and the areas under the summary receiver
      operating characteristic (AUCs-SROC) curve for CEUS and MRI were calculated,
      respectively. Results Seventeen studies with 1142 lesions were included. The
      pooled sensitivity, specificity, positive likelihood ratio, and negative
      likelihood ratio for CEUS /MRI were 0.95/0.92, 0.84/0.91, 5.62/6.74, and
      0.09/0.13, respectively. The AUCs-SROC curves for the two methods were 95.66% and
      94.65%. The subgroup analysis indicated that the scanning slice thickness may
      influence the diagnostic efficacy of MRI. Conclusion Both CEUS and MRI have good
      diagnostic performance for cystic renal masses and can provide the reference for
      clinicians. CEUS is more sensitive but less specific than MRI.

PMID- 29363323
TI  - The tale of two (distal nephron) cell types.

PMID- 29363324
TI  - Chronic nicotine exposure reduces klotho expression and triggers different renal
      and hemodynamic responses in klotho-haploinsufficient mice.
AB  - The klotho gene, which encodes a single-pass transmembrane protein and a secreted
      protein, is expressed predominantly by the distal renal tubules and is related to
      calcium phosphorus metabolism, ion channel regulation, intracellular signaling
      pathways, and longevity. Klotho deficiency aggravates acute kidney injury and
      renal fibrosis. Exposure to nicotine also worsens kidney injury. Here, we
      investigated renal Klotho protein expression in a mouse model of chronic (28-day)
      nicotine exposure, in which mice received nicotine or vehicle (saccharine) in
      drinking water, comparing wild-type (WT) mice, klotho-haploinsufficient ( kl/+)
      mice, and their respective controls, in terms of the effects of that exposure.
      Nicotine exposure was associated with a significant decline in renal Klotho
      expression in WT and kl/+ mice as well as a reduction in the glomerular
      filtration rate in WT mice. Although plasma electrolytes were similar among the
      groups, fractional excretion of sodium was reduced in both nicotine-exposed
      groups. The nicotine-WT mice presented augmented baroreflex sensitivity to
      nitroprusside and augmented sympathetic cardiac modulation. However, nicotine-
      kl/+ mice presented higher plasma levels of urea and aldosterone together with a
      higher alpha-index (spontaneous baroreflex) and higher peripheral sympathetic
      modulation, as evaluated by spectral analysis. We can conclude that nicotine
      downregulates Klotho expression as well as that renal and autonomic responses to
      nicotine exposure are modified in kl/+ mice.

PMID- 29363325
TI  - Short-term high-glucose treatment decreased abundance of Orai1 protein through
      posttranslational mechanisms in rat mesangial cells.
AB  - The short-term effect of high-glucose (HG) treatment on store-operated Ca2+ entry
      in mesangial cells (MCs) is not well-known. The aim of the present study was to
      determine whether and how HG treatment for a short period altered protein
      abundance of Orai1, the channel mediating store-operated Ca2+ entry in MCs. Rat
      and human MCs were exposed to HG (25 mM) for 2, 4, 8, and 24 h, and the abundance
      of Orai1 protein was significantly decreased at the time points of 8 and 16 h.
      Consistently, HG treatment for 8 h significantly reduced store-operated Ca2+
      entry in rat MCs. However, HG treatment for the same time periods did not alter
      the levels of Orai1 transcript. Cycloheximide, a protein synthesis inhibitor, did
      not affect the HG-induced decrease of Orai1 protein, suggesting a
      posttranslational mechanism was involved. However, the HG effect on Orai1 protein
      was significantly attenuated by MG132 (a ubiquitin-proteasome inhibitor) and
      NH4Cl (a lysosomal pathway inhibitor). Furthermore, HG treatment for 8 h
      stimulated ubiquitination of Orai1 protein. We further found that polyethylene
      glycol-catalase, an antioxidant, significantly blunted the HG-induced reduction
      of Orai1 protein. In support of involvement of reactive oxygen species in the HG
      effects, hydrogen peroxide (H2O2) itself significantly decreased abundance of
      Orai1 protein and increased the level of ubiquitinated Orai1. Taken together,
      these results suggest that a short-term HG treatment decreased abundance of Orai1
      protein in MCs by promoting the protein degradation through the ubiquitination
      proteasome and -lysosome mechanisms. This HG-stimulated posttranslational
      mechanism was mediated by H2O2.

PMID- 29363326
TI  - WNT signaling is required for peritoneal membrane angiogenesis.
AB  - The wingless-type mouse mammary tumor virus integration site family (WNT)
      signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT
      signaling pathway in peritoneal membrane injury. We assessed WNT1 protein
      expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD)
      patients and WNT-related gene expression in ex vivo mesothelial cell cultures
      from 21 PD patients. In a transforming growth factor-beta (TGF-beta)-mediated
      animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway
      and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis. WNT1
      and WNT2 gene expression were positively correlated with peritoneal membrane
      solute transport in PD patients. In the mouse peritoneum, TGF-beta-induced
      peritoneal fibrosis was associated with increased expression of WNT2 and WNT4.
      Peritoneal beta-catenin protein was significantly upregulated after infection
      with adenovirus expressing TGF-beta (AdTGF-beta) along with elements of the WNT
      signaling pathway. Treatment with a beta-catenin inhibitor (ICG-001) in mice with
      AdTGF-beta-induced peritoneal fibrosis resulted in attenuation of peritoneal
      angiogenesis and reduced vascular endothelial growth factor. Similar results were
      also observed with the WNT antagonist Dickkopf-related protein (DKK)-1. In
      addition to this, DKK-1 blocked epithelial-mesenchymal transition and increased
      levels of the cell adhesion protein E-cadherin. We provide evidence that WNT
      signaling is active in the setting of experimental peritoneal fibrosis and WNT1
      correlates with patient peritoneal membrane solute transport in PD patients.
      Intervention in this pathway is a possible therapy for peritoneal membrane
      injury.

PMID- 29363327
TI  - Mechanical challenges and cytoskeletal impairments in focal segmental
      glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is a histologically defined form of
      kidney injury typically mediated by podocyte dysfunction. Podocytes rely on their
      intricate actin-based cytoskeleton to maintain the glomerular filtration barrier
      in the face of mechanical challenges resulting from pulsatile blood flow and
      filtration of this blood flow. This review summarizes the mechanical challenges
      faced by podocytes in the form of stretch and shear stress, both of which may
      play a role in the progression of podocyte dysfunction and detachment. It also
      reviews how podocytes respond to these mechanical challenges in dynamic fashion
      through rearranging their cytoskeleton, triggering various biochemical pathways,
      and, in some disease states, altering their morphology in the form of foot
      process effacement. Furthermore, this review highlights the growing body of
      evidence identifying several mutations of important cytoskeleton proteins as
      causes of FSGS. Lastly, it synthesizes the above evidence to show that a better
      understanding of how these mutations leave podocytes vulnerable to the mechanical
      challenges they face is essential to better understanding the mechanisms by which
      they lead to disease. The review concludes with future research directions to
      fill this gap and some novel techniques with which to pursue these directions.

PMID- 29363329
TI  - Retraction Notice.
AB  - At the request of the Journal Editor and the Publisher, the following article has
      been retracted: Lee I. (2015) The effect of postural control intervention for
      congenital muscular torticollis: a randomized controlled trial. Clinical
      Rehabilitation 29(8): 795-802. DOI: 10.1177/0269215514555037. This article
      demonstrates a high level of unreferenced overlap with the following article:
      Rahlin, M. (2005) TAMO Therapy as a Major Component of Physical Therapy
      Intervention for an Infant With Congenital Muscular Torticollis: A Case Report.
      Paediatric Physical Therapy 17(3):L 209-218. 10.1097/01.pep.0000179176.20035.f0.

PMID- 29363330
TI  - Chemical constituents of Geum urbanum L. roots.
AB  - A new dehydrodigallic acid derivative (1), along with 19 known compounds,
      including 6 phenolic derivatives, 2 steroids and 11 triterpenoids were isolated
      from the ethanol extract of the root of Geum urbanum. Herein, there is the first
      report of steroid and triterpene in Geum urbanum. The purified metabolites were
      characterised by NMR spectroscopic and mass spectrometric analyses. The
      identification of the known compounds (2-20) was based on the comparison of their
      NMR spectroscopic features with previously published data. The structural
      characteristics of compound 1 were elucidated by comprehensive 1D and 2D NMR
      spectroscopic methods and acid hydrolysis.

PMID- 29363331
TI  - Enalapril decreases rat plasma concentration of TMAO, a gut bacteria-derived
      cardiovascular marker.
AB  - INTRODUCTION: Increased plasma level of trimethylamine N-oxide (TMAO), a
      bacterial metabolite of choline, is associated with an increased cardiovascular
      risk. Indoxyl sulfate, a bacterial metabolite of tryptophan, is thought to be
      associated with higher mortality in cardiorenal syndrome. We hypothesized that
      enalapril, a well-established drug reducing cardiovascular mortality, may affect
      the plasma level of gut bacteria-derived metabolites and gut bacteria
      composition. MATERIALS AND METHODS: 14-16-week-old Wistar rats were maintained
      either on water (controls) or water solution of enalapril for two weeks (5.3 or
      12.6 mg/kg b.w.). Blood plasma and urine were analyzed for the concentration of
      TMAO and indoxyl sulfate using liquid chromatography coupled with triple
      quadrupole mass spectrometry. Gut bacteria composition was analyzed with 16S rRNA
      gene sequence analysis. RESULTS: Rats treated with enalapril showed a
      significantly lower plasma TMAO level and a trend towards higher 24 h urine
      excretion of TMA and TMAO. Plasma indoxyl level was similar between the groups.
      There was no significant difference between the groups in gut bacteria
      composition. CONCLUSIONS: Enalapril decreases rat plasma TMAO, but does not
      affect the plasma level of indoxyl sulfate and gut bacteria composition. The
      enalapril-induced decrease in plasma TMAO level may be of therapeutic and
      diagnostic importance.

PMID- 29363332
TI  - The application of improved abdominal wall punctures technique in
      ventriculoperitoneal shunt for hydrocephalus: a retrospective analysis versus
      open mini-laparotomy.
AB  - PURPOSE: Ventriculoperitoneal shunt (VPS) remains as one of the main treatment
      for hydrocephalus. The traditional technique for placing the distal ends of
      shunts is via a mini-laparotomy. However, laparotomies are relatively time
      consuming. Trocars to penetrate abdominal wall by blind puncture have been used.
      Here, we report on the abdominal wall puncture technique, and compare the
      possible complications and outcomes with traditional mini-laparotomy. MATERIALS
      AND METHODS: We use a 5mm incision at the inverse McBurney point. The abdominal
      wall on both sides of the incision point is lifted with two towel clips prior to
      puncture to create a potential gap between the abdominal wall and viscera. After
      the puncture, a guide wire is inserted followed by a dilator, introducer and the
      distal shunt tubing using a Seldinger technique. In this process, the operator
      feels resistance give with breakthrough of parietal peritoneal. After the
      insertion of introducer, a negative pressure injection test helps confirm whether
      the introducer is inside the peritoneum. RESULTS: Operative time is less than
      with mini-laparotomies. Postoperative abdominal symptoms are mild. Out of 29
      patients there were no puncture related complications. CONCLUSION: The improved
      abdominal-wall puncture technique is a simple, fast, economical and effective
      method. Patients, who are treated by the method, generally experience rapid
      postoperative recoveries.

PMID- 29363328
TI  - Molecular physiology and pathophysiology of stromal interaction molecules.
AB  - Ca2+ release from the endoplasmic reticulum is an important component of Ca2+
      signal transduction that controls numerous physiological processes in eukaryotic
      cells. Release of Ca2+ from the endoplasmic reticulum is coupled to the
      activation of store-operated Ca2+ entry into cells. Store-operated Ca2+ entry
      provides Ca2+ for replenishing depleted endoplasmic reticulum Ca2+ stores and a
      Ca2+ signal that regulates Ca2+-dependent intracellular biochemical events.
      Central to connecting discharge of endoplasmic reticulum Ca2+ stores following G
      protein-coupled receptor activation with the induction of store-operated Ca2+
      entry are stromal interaction molecules (STIM1 and STIM2). These highly
      homologous endoplasmic reticulum transmembrane proteins function as sensors of
      the Ca2+ concentration within the endoplasmic reticulum lumen and activators of
      Ca2+ release-activated Ca2+ channels. Emerging evidence indicates that in
      addition to their role in Ca2+ release-activated Ca2+ channel gating and store
      operated Ca2+ entry, STIM1 and STIM2 regulate other cellular signaling events.
      Recent studies have shown that disruption of STIM expression and function is
      associated with the pathogenesis of several diseases including autoimmune
      disorders, cancer, cardiovascular disease, and myopathies. Here, we provide an
      overview of the latest developments in the molecular physiology and
      pathophysiology of STIM1 and STIM2. Impact statement Intracellular Ca2+ signaling
      is a fundamentally important regulator of cell physiology. Recent studies have
      revealed that Ca2+-binding stromal interaction molecules (Stim1 and Stim2)
      expressed in the membrane of the endoplasmic reticulum (ER) are essential
      components of eukaryote Ca2+ signal transduction that control the activity of ion
      channels and other signaling effectors present in the plasma membrane. This
      review summarizes the most recent information on the molecular physiology and
      pathophysiology of stromal interaction molecules. We anticipate that the work
      presented in our review will provide new insights into molecular interactions
      that participate in interorganelle signaling crosstalk, cell function, and the
      pathogenesis of human diseases.

PMID- 29363333
TI  - Poverty and Health Disparities: What Can Public Health Professionals Do?
AB  - More than a tenth of the U.S. population (13% = 41 million people) is currently
      living in poverty. In this population, the socioeconomic, cultural, and
      environmental conditions have detrimental health effects such as higher rates of
      chronic diseases, communicable illnesses, health risk behaviors, and premature
      mortality. People living in poverty are also deprived of social, psychological,
      and political power, leading to continuation of worsening health and chronic
      deprivation over generations. The health of individuals living in poverty poses
      greater challenges from policy, practice, and research standpoints. Public health
      professionals are poised uniquely to be advocates for the marginalized, be the
      resource persons for health education, implement health promotion programs, and
      conduct research to understand health effects of poverty and design tailored and
      targeted public health interventions. In this article, we summarize the
      opportunities for public health practice with individuals living in poverty.

PMID- 29363334
TI  - Community-Clinical Linkages With Community Health Workers in the United States: A
      Scoping Review.
AB  - Despite the proliferation of community-clinical linkage (CCL) interventions with
      community health workers (CHWs), little is known about the components of these
      programs or how linkages are realized. In this scoping review, we synthesize
      evidence concerning the role of CHWs in creating and sustaining CCLs aimed at
      improving individual health outcomes. Our inclusion criteria included peer
      reviewed articles that described a CHW intervention in the United States that
      used a CCL model. A total of 2,776 titles and/or abstracts were screened and 47
      articles underwent full text review. Two independent reviewers rated the screened
      articles based on additional criteria including the CHW connection to community
      and evidence of linkage follow up rather than simple referral. For the 11 peer
      reviewed articles included in the final review, we describe the CHW's
      relationship to the community, training, and role within the intervention,
      linkage, and outcomes. We used a standardized framework to determine
      commonalities in CHW roles across the interventions. CCLs with CHWs positively
      affect the delivery of both clinical care and community resources across a range
      of disease areas in a variety of contexts. To identify effective CCL models,
      additional information on CHW training, CCL follow-up methods, and the CHW role
      in CCLs is recommended.

PMID- 29363335
TI  - Novel models for Parkinson's disease and their impact on future drug discovery.
AB  - INTRODUCTION: Parkinson's disease is a progressive neurodegenerative disease that
      affects millions of elderly individuals worldwide. Despite intensive efforts
      dedicated to find a better treatment, the pathogenesis of Parkinson's Disease
      remains unknown. In search for a better therapy for the disease, several new in
      vivo and in vitro models of Parkinson's disease have been developed in recent
      times. Areas covered: The authors provide an outline of the various traditional
      models of Parkinson's disease and address those that have been recently
      generated. They also discuss the utility of these models for the identification
      of drugs of potential therapeutic value for Parkinson's Disease patients. From
      the cell based models and the well-known toxin-based animal models, to the recent
      genetic models and the increasingly used non-mammalian models, every model is
      worthwhile in the search for a better Parkinson's Disease therapy. Expert
      opinion: Almost 60 years after its discovery, levodopa is still the gold standard
      treatment for Parkinson's Disease patients. It seems unlikely that a single model
      can fully recapitulate the complexity of Parkinson's Disease in the same way it
      appears improbable that a unique treatment could relieve both the motor and non
      motor symptoms of Parkinson's Disease altogether. Therefore treatment will
      probably require a combination of therapies.

PMID- 29363336
TI  - Involvement of people with dementia in raising awareness and changing attitudes
      in a dementia friendly community pilot project.
AB  - Low levels of public understanding can contribute to the fear, stigma and social
      exclusion associated with living with dementia. Dementia friendly communities aim
      to address this by empowering people with dementia and increasing their social
      inclusion. As a part of a Community Based Participatory Action Research (CBPAR)
      process, a multicomponent dementia friendly community intervention supported:
      research; the establishment of a Dementia Advisory Group and Alliance; an
      awareness campaign and education in community organisations. Educational events
      were co-designed and co-facilitated by people with dementia and their care
      partners. To assess project reach and changes in attitudes of community members,
      two cross sectional surveys were conducted with adults (aged over 18 years) using
      validated scales. Independent samples t-tests compared responses to the surveys
      prior to the commencement of the project (2014) and two years later (2016). In
      2016, respondents showed increased agreement with the statements: 'People with
      dementia participate in a wide variety of activities and interests,' and, 'It is
      easy to find out about dementia friendly services or organisations in Kiama'.
      Respondents who attended an educational event reported less negative views about
      how they themselves would feel if they were diagnosed with dementia compared with
      respondents who did not attend an event. CBPAR appears useful to support the
      involvement of people with dementia and the engagement of the community to
      improve awareness of dementia services. The direct involvement of people living
      with dementia as spokespeople and educators was an effective way to improve
      positive attitudes and reduce the negative stereotypes associated with living
      with dementia. Further research is needed to compare different approaches to the
      creation of dementia friendly communities in different locations, and to
      establish the extent to which local interventions are useful to complement
      efforts to raise awareness of dementia at a national level.

PMID- 29363337
TI  - Pharmacokinetic drug evaluation of daclizumab for the treatment of relapsing
      remitting multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory demyelinating
      disease of the central nervous system. Despite the availability of several
      disease-modifying therapies for relapsing MS, there is a need for highly
      efficacious targeted therapy with a favorable benefit-risk profile and a high
      level of treatment adherence. Daclizumab is a humanized monoclonal antibody
      directed against CD25, the alpha subunit of the high-affinity interleukin 2 (IL
      2) receptor, that reversibly modulates IL-2 signaling. Areas covered: Daclizumab
      blocks the activation and expansion of autoreactive T cells that plays a role in
      the immune pathogenesis of MS. As its modulatory effects on the immune system,
      daclizumab's potential for use in MS was tested extensively showing a high
      efficacy in reducing relapse rate, disability progression and the number and
      volume of gadolinium-enhancing lesions on brain magnetic resonance imaging.
      Moreover, phase II and III trials showed a favorable pharmacokinetic (PK) profile
      with slow clearance, linear pharmacokinetics at doses above 100 mg and high
      subcutaneous bioavailability, not influenced by age, sex or other clinical
      parameters. Expert opinion: Among the new emerging drugs for MS, daclizumab also,
      thanks to a favorable PK profile, may represent an interesting and promising
      therapeutic option in the wide MS therapies armamentarium.

PMID- 29363338
TI  - Ineffective Health Management in Hemodialysis Patients: Diagnostic Accuracy
      Study.
AB  - This study analyzed the accuracy of clinical indicators of ineffective health
      management in hemodialysis patients. A diagnostic accuracy study was performed in
      200 chronic kidney disease patients undergoing hemodialysis during the first half
      of 2015. Measures of sensitivity and specificity were calculated using latent
      class analysis. Ineffective health management was present in 66.28% of patients.
      Accurate clinical indicators included expressed nonadherence to treatment, daily
      life choices ineffective to achieve health goals, expression of difficulty with
      prescribed regimens, inappropriate use of medicines, lack of expression of
      willingness to control the disease, irregular attendance of dialysis sessions,
      and infection. Hemodialysis may trigger a set of clinical indicators that predict
      the presence of ineffective health management. This knowledge provides evidence
      to clinical practices for hemodialysis patients and contributes to the best
      clinical performance of nurse practitioners.

PMID- 29363339
TI  - Effects of a Nurse-Led, Stage-Matched, Tailored Program for Smoking Cessation in
      Health Education Centers: A Prospective, Randomized, Controlled Trial.
AB  - The purpose of this study was to examine the effectiveness of a stage-matched
      intervention performed at outpatient clinics. Participants were randomly assigned
      to an intervention group (IG) or usual care group (UCG). The trial was targeted
      on smoking patients with coronary heart disease or diabetes. After completing the
      3-month intervention, both groups received a telephone follow-up at 6 months.
      This analysis showed that the outcomes of the IG for the 7-day point prevalence
      (PP) of abstinence (odds ratio [OR] = 2.00; p = .001) and 30-day PP (OR = 2.27; p
      = .004) at 6 months were significantly better than the UCG. Stage of change (OR =
      4.06; p < .001) and decreased daily cigarette consumption by 50% at 6 months (OR
      = 2.26; p = .019) outcomes also improved significantly. The preliminary results
      showed that a nurse-led cessation intervention in clinics may be an effective
      approach to help outpatients quit smoking.

PMID- 29363340
TI  - HIV status disclosure among postpartum women in rural Tanzania: predictors,
      experiences and uptake of a nurse-facilitated disclosure intervention.
AB  - HIV status disclosure is a key support strategy to start and maintain HIV care
      and treatment and to reduce HIV transmission. We explored the patterns and
      correlates of disclosure and described the effectiveness of nurse-facilitated
      disclosure among HIV-infected mothers of infants in coastal Tanzania. We enrolled
      400 HIV positive women in an observational longitudinal study in 2011,
      interviewed them about maternal sociodemographic and economic characteristics,
      maternal and child health and history of HIV disclosure experiences and offered
      nurse-facilitated HIV disclosure at enrolment or at follow-up 1 month later.
      Mothers frequently disclosed their status to husbands and/or female relatives and
      experienced predominantly positive reactions. Economically vulnerable women
      disclosed more often to elderly female relatives, indicating that Infant and
      Young Child Feeding counseling given to HIV positive women should garner the
      support of elderly female relatives for implementing appropriate feeding
      practices. Nurse-facilitated disclosure was feasible in this low resource setting
      and was used by patients to help them with both first-time disclosure and
      disclosure to new persons.

PMID- 29363341
TI  - Physiotherapy treatment of the diabetic shoulder: health-related quality of life
      and measures of shoulder function regarding patients with type 1 diabetes.
AB  - PURPOSE: The aim of this study was to investigate how health-related quality of
      life (HRQoL) and functional shoulder range of motion are affected among patients
      with diabetes with shoulder problems, treated with a specific physiotherapy
      programme. A further aim was to investigate how health-related quality of life,
      functional shoulder range of motion, pain intensity, and shoulder function
      correlate within the group of patients after the treatment period. METHOD: A pre
      post treatment design was applied for a study group of ten patients with type 1
      diabetes and shoulder problems. The physiotherapy treatment consisted of
      exercises promoting enhanced micro-circulation in the shoulder tissues, optimal
      shoulder co-ordination, and muscle relaxation. The Short Form-36 (SF-36),
      shoulder range of motion measures, the Shoulder Rating Scale - Swedish version,
      and pain intensity measures were used. The results regarding SF-36 were compared
      with the results of a control group of patients having either type 1 or type 2
      diabetes and shoulder problems that did not receive any specific physiotherapy
      treatment. RESULTS: As a potential result of physiotherapy training, a
      significant change towards higher scores was observed in the physical component
      summary (PCS) measure of SF-36. There was a significant improvement regarding PCS
      in the study group as compared with the control group. There were negative
      correlations between the four aspects of pain intensity and PCS and Shoulder
      Rating Scale - Swedish version, respectively, but a positive correlation between
      PCS and Shoulder Rating Scale - Swedish version. "Hand-raising" and "hand-behind
      back" were significantly improved, and proved to be positively correlated with
      Shoulder Rating Scale - Swedish version. CONCLUSIONS: The results of this study
      indicate that patients with type 1 diabetes and shoulder problems, treated with a
      specific physiotherapy programme, may improve with respect to physical aspects of
      health-related quality of life, and partially regain their range of motion in the
      shoulder joint. Based on these results, the associated treatment protocol may be
      recommended for physiotherapy treatment in such patients. Implications for
      Rehabilitation Diabetes is a significant risk factor in the development of
      shoulder pain and disability. Health-related quality of life (HRQoL) is affected
      in patients with diabetes and shoulder problems. A specific physiotherapy
      programme may improve physical aspects of HRQoL in patients with diabetes and
      shoulder problems. Specific physiotherapy intervention may also improve range of
      motion in the shoulder joint in patients with diabetes and shoulder problems.

PMID- 29363342
TI  - The effect of beta glucan on MTX induced testicular damage in rats.
AB  - We investigated the histopathological effects of methotrexate (MTX), a
      chemotherapeutic agent, and beta glucan (BG), an antioxidant, on rat testis. We
      used four groups of Sprague-Dawley male rats: MTX, MTX + BG, BG, and control. The
      MTX group was exposed to a single dose of MTX on the first day of experiment. The
      MTX + BG group was exposed to a single dose of MTX and BG on the first day of
      experiment followed by BG for 4 additional days. The BG group was exposed to BG
      for 5 days. The control group was given saline for 5 days. On day five, all
      animals were sacrificed and testicular tissue was evaluated for histopathology
      and the terminal deoxynucleotidyl transferase (TdT) deoxyuridine triphosphate
      nick-end labeling assay (TUNEL) was used to detect apoptosis. The apoptotic index
      (AI) and testicular damage increased in the MTX group compared to the other three
      groups. Histopathology was reduced in the MTX + BG group compared to the MTX
      group. Seminiferous tubule diameter was reduced in the MTX group compared to the
      BG group; we found no difference between control and BG groups. The thickness of
      th e germinal epithelium was reduced in the MTX group compared to the other
      groups. We found no difference in testicular weight among the groups. We compared
      body weight before and after the experiment; weights in the MTX and MTX + BG
      groups were significantly reduced compared to controls. In the control groups, we
      found a statistically significant increase in body weight, whereas there was no
      change in the BG group. We found that MTX causes deleterious effects on
      testicular tissue and that beta glucan may be protective.

PMID- 29363343
TI  - Fevipiprant in the treatment of asthma.
AB  - INTRODUCTION: Asthma is common and in many, particularly those with more severe
      disease, there remains a substantial unmet need. Success with biologics targeting
      eosinophilic inflammation underscore the value of treating inflammation in asthma
      beyond corticosteroids. Fevipiprant (QAW039) is an oral treatment for asthma. It
      competitively and reversibly antagonises the prostaglandin D2 receptor 2 (DP2)
      expressed on inflammatory and structural cells. Areas covered: We reviewed
      fevipiprant's mode of action and efficacy against other current and emerging
      pharmacological interventions for moderate-to-severe asthma. We undertook a
      literature review using the PubMed/Medline database, the U.S. National Library of
      Medicine's Clinical Trials website and from manufacturers' press releases with
      the search terms: 'QAW039', 'Fevipiprant', 'CRTH2 antagonists', 'DP2', 'DP1',
      'monoclonal antibody', 'eosinophil' with 'asthma' plus the names of individual
      drugs. Three Phase 2 trials have been conducted and three Phase 3 trials
      (NCT02563067, NCT03052517, NCT02555683) are in progress. To date Fevipiprant's
      greatest success has been in targeting severe eosinophilic asthma. Expert
      opinion: Fevipiprant presents the possibility of a new orally active therapy for
      asthma. If successful in phase 3 trials it will have an enormous impact on the
      treatment paradigm for asthma and will potentially widen access for pre-biologic
      treatment to a larger population.

PMID- 29363344
TI  - Association between gestational diabetes and biomarkers: a role in diagnosis.
AB  - BACKGROUND: We investigated the association between markers of insulin
      resistance, chronic inflammation, and adipokines and GDM. METHODS: In our case
      cohort study in Johannesburg we included women with GDM and controls. We tested
      the ability of biomarkers to identify women at high risk of GDM. RESULTS: Of the
      262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p = 0.04)
      and had more clinical risk factors (p = 0.008). We found a significant difference
      in fasting insulin (p < 0.001), adiponectin (p = 0.046), HOMA (p < 0.001) and
      QUICKI (p < 0.001). HOMA (AUROC = 0.82) or QUICKI (AUROC = 0.82) improved the
      ability of risk factors to identify women at high risk of GDM. CONCLUSIONS:
      Insulin sensitivity markers are promising tools to identify women at high risk of
      GDM.

PMID- 29363345
TI  - Androgenetic alopecia; drug safety and therapeutic strategies.
AB  - INTRODUCTION: Androgenetic alopecia (AGA) is a benign condition with variable
      psychosocial impact, with some individuals adapting well while others needing
      therapeutic support. Although 5alpha-reductase inhibitors like finasteride and
      dutasteride have proven effective in ameliorating AGA, their use/selection is
      currently a subject of debate. Areas covered: Treatment of AGA with 5alpha
      reductase inhibitors lead to variable adverse effects and relatively unstable
      results (therapeutic efficacy ending with treatment cessation), so the choice of
      optimal therapy is not straightforward. This paper presents a general perspective
      regarding AGA based on studies listed in PubMed, to better understand/appreciate
      the opportunity for long term use of medication for a biological condition having
      non-life threatening implications. Studies focussed on adverse effects suggest
      that finasteride should be used with caution in AGA, due to considerable and
      persistent side effects induced in some men. In contrast, efficacy data indicate
      that dutasteride (a stronger inhibitor) presents superior therapeutic results
      compared to finasteride. Expert opinion: This paper argues that finasteride
      should be preferred to dutasteride in the treatment of AGA. Thus, finasteride
      preserves important physiological roles of dihydrotestosterone (unrelated to AGA)
      and, in addition, its adverse effects seem to be (at least in part) predictable.

PMID- 29363346
TI  - Pediatric nondura-based clear cell meningioma of the cauda equina: case report
      and review of literature.
AB  - Although spinal meningiomas are uncommon in children, clear cell meningioma has
      been described as the most common variant of spinal meningiomas in the pediatric
      age group. 24 cases of pediatric spinal clear call meningioma have been reported
      in the literature. We report one case and review the literature regarding
      pediatric spinal clear cell meningioma.

PMID- 29363347
TI  - Biotransformation of (+)-isofraxinellone by Aspergillus niger and insect
      antifeedant activity.
AB  - The biotransformation of (+)-isofraxinellone (1) by Aspergillus niger was
      investigated. Compound 1 was transformed to only one new compound 2. The
      structure of 2 was identified as (-)-(4S)-4-hydroxyisofraxinellone which was
      regio- and stereo-selective hydroxylated at the C-4 position by IR, EI-MS 1D and
      2D NMR. Absolute configuration of hydroxyl group at the C-4 position was detected
      by modified Mosher's method. Antifeedant activity of compounds 1 and 2 against
      larvae of Spodoptera litura was assayed. These compounds showed potent
      antifeedant activity and ED50 (50% of effective dose) values were 3.91 and 4.43
      MUg/cm2, respectively.

PMID- 29363348
TI  - Reliability of internal and external load parameters in recreational football
      (soccer) for health.
AB  - There is limited research focussed around the analysis of internal and external
      load parameters during football health programmes. The aim of this study was to
      assess the reliability of internal and external load parameters in this activity.
      Thrity subjects were enrolled (mean +/- SDs; age = 43 +/- 3 years, weight = 84 +/
      14 kg, height = 176 +/- 7 cm, BMI = 27.1 +/- 3, VO2max = 40.7 +/- 3.4 ml.kg.min
      1). The football matches (five a-side) took place on an artificial grass outdoor
      field (pitch size of 36 * 18.5 m). Participants completed the match (60 min) and
      replicated the same match a week later. The analysis took into account several
      parameters: heart rate (HR), total distance (TD), high speed running (HSR),
      number of accelerations (>2 m.s-2) and metabolic power (MP). We found a good
      score of reliability in several parameters: TD (ICC = 0.66), accelerations (ICC =
      0.62), mean HR (ICC = 0.82), HSR (ICC = 0.77) and MP (ICC = 0.66). The results
      reported in this study revealed good scores of absolute reliability and
      small/trivial effect size.

PMID- 29363350
TI  - Visual failure and sinus thrombosis following depressed skull fracture:
      management with single session lumboperitoneal shunt and sinus decompression 
      case report.
AB  - Elevation of a depressed skull fracture (DSF) overlying a venous sinus is
      generally avoided due to risk of sinus injury. Rarely, the sinus may be
      compressed by the fractured segment, causing intracranial hypertension (IH) or
      encephalopathy and can only be diagnosed with cerebral angiography or MR imaging
      techniques. The posterior third of the superior sagittal sinus (SSS) was found
      involved in all the reported cases. There is no consensus on its management, but
      most patients did not have any sinus thrombosis and improved after elevation of
      the compressing DSF alone. There are isolated reports of improvement with serial
      lumbar punctures or ventriculoperitoneal shunt. We report for the first time, a
      single session lumboperitoneal shunt and DSF elevation for a patient with
      thrombosis of the posterior part of SSS due to an overlying DSF, causing florid
      papilledema and impending blindness. Elevation of the DSF alone would not have
      achieved patency of the thrombosed sinus immediately to save his vision. Hence a
      lumboperitoneal shunt was done for immediate relief of IH. This CSF diversion
      alone was insufficient to achieve patency of the thrombosed sinus in the presence
      of significant external compression by the DSF; even if anticoagulants were used.
      Hence we elevated the DSF after craniotomy using a technical modification; by
      making a wide gutter circumferentially around the DSF with a high speed drill, to
      avoid sinus injury; prior to its elevation. The patient's vision improved in 48
      hours and anticoagulants were used till 2 months when sinuses were found normal
      on MRI. Serial CT &MR images showing progression to thrombosis and recovery after
      decompression are presented. Both CSF diversion and DSF elevation are necessary
      when vision is threatened by IH due to sinus thrombosis with an overlying DSF.

PMID- 29363349
TI  - Drug metabolism in early infancy: opioids as an illustration.
AB  - INTRODUCTION: Drug dosing in infants frequently depends on body weight as a crude
      indicator for maturation. Fentanyl (metabolized by Cytochrome P450 3A4) and
      morphine (glucuronidated by UDP-glucuronosyltransferase-2B7) served as model
      drugs to provide insight in maturation patterns of these enzymes and provide
      understanding of the impact of non-maturational factors to optimize dosing in
      infants. Areas covered: Systematic searches on metabolism and population
      pharmacokinetic (Pop-PK) models for fentanyl and morphine were performed. Pre-
      and post-model selection criteria were applied to assess and evaluate the
      validity of these models. It was observed that maturational changes have been
      rather well investigated, be it with variability in the maturational function
      estimates. The same holds true for Pop-PK models, where non-maturational
      covariates have also been reported (pharmacogenetics, disease state or external
      influences), although less incorporated in the PK models and with limited
      knowledge on mechanisms involved. Expert opinion: PK models for fentanyl and
      morphine are currently available. Consequently, we suggest that researchers
      should not continue to develop new models, but should investigate whether
      collected data fit in already existing models and provide additional value
      concerning the impact of (non)-maturational factors like drug-drug interactions
      or pharmacogenetics.

PMID- 29363351
TI  - Mitogen-activated protein kinase (MEK) inhibitors to treat melanoma alone or in
      combination with other kinase inhibitors.
AB  - INTRODUCTION: Malignant melanoma (MM) is an aggressive disease with a rapidly
      rising incidence due to neoplasm of melanocytes. Molecular targeted therapies
      have demonstrated lower toxicity and improved overall survival versus
      conventional therapies of MM. The revealing of mutations in the BRAF/MEK/ERK
      pathway has led to the development of BRAF inhibitors such as vemurafenib and
      dabrafenib for the treatment of cutaneous MM. Though, progression of resistance
      to these agents has prompted attempts to target downstream proteins in this
      pathway. Trametinib, a MEK1/2 inhibitor, was approved in 2013 for the treatment
      of BRAF V600E/K mutation-positive unresectable or metastatic cutaneous melanoma
      patients. Areas covered: The aim of the current review is to present an update on
      the role of MEK in progressive melanomas and summarize latest results of clinical
      studies with innovative MEK inhibitors and/or combined approaches with other
      kinase inhibitors such as BRAF inhibitors in the treatment of MM. Expert opinion:
      Two combined treatments (i.e. trametinib plus dabrafenib and vemurafenib plus
      cobimetinib) target two different kinases in the BRAF/MEK/ERK pathway. The
      simultaneous prohibition of both MEK and BRAF is associated with more durable
      response rate than BRAF monotherapy and can overcome acquired resistance.

PMID- 29363352
TI  - Anticoagulant and antiplatelet therapy choices for patients with atrial
      fibrillation one year after coronary stenting or acute coronary syndrome.
AB  - INTRODUCTION: Guidelines recommend a combined anticoagulant and antiplatelet
      approach for patients with atrial fibrillation (AF) after coronary stenting (CS)
      or acute coronary syndrome (ACS). Finding the optimal balance of reducing
      ischemic risk and minimizing bleeding risk is challenging. Recent trials have
      evaluated a variety of regimens for up to one year for AF patients after CS/ACS.
      Little empiric evidence exists about the best antithrombotic strategy beyond one
      year. Areas covered: In this review two key areas are covered. First, a summary
      of the overall risk and benefits of anticoagulant and antiplatelet therapy in
      patients with AF and CS or ACS is provided. Second, despite limited empiric
      evidence to guide therapeutic decisions for combined anticoagulant and
      antiplatelet therapy in patients with AF one year after CS/ACS we provide
      guidance for shared patient-physician decision making. Expert opinion: The
      evidence is limited. For all patients with AF and stable CAD (>=1 year after CS
      or ACS) the risk for thromboembolism, cardiovascular events and bleeding should
      be assessed individually. For patients with low bleeding risk and high risk for
      cardiovascular events, antiplatelet therapy might be added to anticoagulant
      therapy.

PMID- 29363353
TI  - Varenicline-Induced Panic Disorder in a Previously Healthy Patient.

PMID- 29363354
TI  - Clinical Toxicology of Yew Poisoning.
AB  - OBJECTIVES: Yew plant materials contain highly toxic taxine alkaloids. Serious
      ingestions can result in life-threatening toxicity. The purpose of this article
      is to summarize the literature on the treatment of acute yew poisoning. DATA
      SOURCES: PubMed (January 1946 to November 2017) was searched using the search
      terms "taxus/po". EMBASE (1980 to November 2017) was searched using the search
      terms "taxus/to" and "yew.mp." Web of Science (1945 to November 2017) was
      searched using the text words taxus, taxine, and yew. STUDY SELECTION AND DATA
      EXTRACTION: Available English language articles involving case reports,
      epidemiology, treatment, and outcomes were included. DATA SYNTHESIS: Although not
      uncommon, unintentional yew poisoning rarely results in significant morbidity or
      mortality. A total of 26 case reports of yew poisoning were evaluated along with
      4 case series articles (totaling 22 additional cases). Only 4 of the 48 total
      cases (8%) were accidental poisonings, the rest being deliberate ingestions. In
      20 patients (42%), it resulted in fatalities. Severe, acute yew poisoning results
      in symptomatology largely resistant to pharmacotherapy intervention. CONCLUSIONS:
      Most nonintentional ingestions of yew plant constituents are asymptomatic and
      require little intervention. Severe poisoning can result in life-threatening
      cardiac toxicity and require aggressive supportive care. Therapeutic
      interventions, such as sodium bicarbonate, digoxin immune fab, and hemodialysis
      that have been utilized in case studies and case series in the literature have
      little proven benefit. Extracorporeal life support should be considered in severe
      yew poisoning.

PMID- 29363355
TI  - Biologic-Induced Infections in Inflammatory Bowel Disease: The TNF-alpha
      Antagonists.
AB  - OBJECTIVE: To review the mechanism and association of infectious risk among the
      tumor-necrosis factor alpha (TNF-alpha) antagonists used in inflammatory bowel
      disease. DATA SOURCES: A PubMed literature search was performed using the
      following search terms: infliximab, adalimumab, certolizumab, golimumab,
      inflammatory bowel disease, crohn's, ulcerative colitis, adverse effects, adverse
      events, safety, and infection. STUDY SELECTION AND DATA EXTRACTION: Meta-analyses
      and cohort studies with outcomes pertaining to quantitative infectious risk were
      reviewed. Case reports and case series describing association between TNF-alpha
      inhibitors and infection were also reviewed. DATA SYNTHESIS: A total of 7 recent
      meta-analyses of randomized trials demonstrate inconclusive association of
      infection with TNF-alpha antagonists. Registry data suggest that medications
      carry an independent risk of opportunistic infections. Risk factors for infection
      include older age, malnutrition, diabetes, and possibly combination therapy.
      Reported infections vary widely but include intracellular and granulomatous
      bacteria, viruses, and fungi. CONCLUSION: TNF-alpha antagonists are associated
      with an increased risk of opportunistic infection, although this risk has not
      been demonstrated conclusively in randomized controlled trials. Knowledge of
      concomitant risk factors, mechanism of infectious risk, and available treatment
      options can improve patient care in the clinical setting.

PMID- 29363357
TI  - Clinical Application of Mathematical Long Bone Ratios to Calculate Appropriate
      Donor Limb Lengths in Bilateral Upper Limb Transplantation.
AB  - BACKGROUND: Limited methods exist to aid in deciding the appropriate donor limb
      lengths in bilateral upper limb amputees qualifying for vascularized composite
      allotransplantation. We hypothesized mathematical equations could be created
      using long bone length ratios, and applied to radiographs, to approximate the
      patient's limb length prior to amputation. METHODS: A data set of 30 skeletons'
      unilateral upper limb long bones measured using osteometric board and calipers
      was used. Anatomic segment ratios were calculated based on humerus length after
      multivariate linear regression analysis. For clinical application testing, 5
      cadavers' upper limbs were radiographed. Radiographic bone lengths were then
      measured along the long axis of each long bone. These measured radiographic
      lengths were then compared with the predicted bone lengths, generated from the
      skeleton data set ratios, for each cadaver. RESULTS: The chi-square goodness-of
      fit test showed excellent fit ( P < .01) between the predicted and
      radiographically measured lengths for the 5 cadavers, and interobserver
      measurements showed no statistical difference. Depending on the cadaver, percent
      error in total limb length predicted to measure ranged from 0.9% to 2.7%. The
      variables to multiply an individual humerus length to calculate a given anatomic
      segment thus proved to be effective. CONCLUSIONS: If a bilateral upper limb
      amputee has 1 intact humerus, ratios to the humerus length can be reliably
      applied to calculate the preamputation limb length based on the patient's
      radiographic humerus length. These formulas are indicated for finding the
      appropriate limb lengths, and smaller anatomic segments, for donor-recipient
      matching in upper limb transplantation.

PMID- 29363356
TI  - Sedative Plasma Concentrations and Delirium Risk in Critical Illness.
AB  - BACKGROUND: The relationship between plasma concentration of sedatives and
      delirium is unknown. OBJECTIVE: We hypothesized that higher plasma concentrations
      of lorazepam are associated with increased delirium risk, whereas higher plasma
      concentrations of dexmedetomidine are associated with reduced delirium risk.
      METHODS: This prospective cohort study was embedded in a double-blind randomized
      clinical trial, where ventilated patients received infusions of lorazepam and
      dexmedetomidine. Plasma concentrations of these drugs and delirium assessments
      were measured at least daily. A multivariable logistic regression model
      accounting for repeated measures was used to analyze associations between same
      day plasma concentrations of lorazepam and dexmedetomidine (exposures) and the
      likelihood of next-day delirium (outcome), adjusting for same-day mental status
      (delirium, coma, or normal) and same-day fentanyl doses. RESULTS: This critically
      ill cohort (n = 103) had a median age of 60 years (IQR: 48-66) with APACHE II
      score of 28 (interquartile range [IQR] = 24-32), where randomization resulted in
      assignment to lorazepam (n = 51) or dexmedetomidine (n = 52). After adjusting for
      same-day fentanyl dose and mental status, higher plasma concentrations of
      lorazepam were associated with increased probability of next-day delirium
      (comparing 500 vs 0 ng/mL; odds ratio [OR] = 13.2; 95% CI = 1.4-120.1; P = 0.02).
      Plasma concentrations of dexmedetomidine were not associated with next-day
      delirium (comparing 1 vs 0 ng/mL; OR = 1.1; 95% CI = 0.9-1.3; P = 0.45).
      CONCLUSIONS: In critically ill patients, higher lorazepam plasma concentrations
      were associated with delirium, whereas dexmedetomidine plasma concentrations were
      not. This implies that the reduced delirium risk seen in patients sedated with
      dexmedetomidine may be a result of avoidance of benzodiazepines, rather than a
      dose-dependent protective effect of dexmedetomidine.

PMID- 29363358
TI  - Analysis of National Institutes of Health Funding in Hand Surgery.
AB  - BACKGROUND: Federal research dollars help investigators develop biomedical
      therapies for human diseases. Currently, the state of funding in hand surgery is
      poorly understood. This study defines the portfolio of National Institutes of
      Health (NIH) grants awarded in hand surgery. METHODS: This was a cross-sectional
      study of hand surgeons in the US. Faculty members of accredited hand surgery
      fellowships and/or members of the American Society for Surgery of the Hand were
      queried in the NIH RePORT database for awards obtained during 2005-2015. RESULTS:
      Of 2317 hand surgeons queried, only 18 obtained an NIH grant (0.8%). Thirty-eight
      unique grants were identified totaling $42 197 375. R01 awards comprised the
      majority of funding (78.0%) while K08 awards accounted for 1.1%. The K-to-R
      transition rate was zero. The National Institute of Arthritis and Musculoskeletal
      and Skin Disease supported the most funding (65.2%), followed by the National
      Institute of Neurological Disorders and Stroke (30.8%). There was no
      statistically significant difference in NIH funding totals with hand surgeon
      characteristics. Funding supported translational (46.0%), basic science (29.6%),
      clinical (21.0%), and education-based (3.4%) research. Peripheral nerve (33.3%)
      and bone and joint disease (30.1%) received the most research funding.
      CONCLUSIONS: Less than 1% of hand surgeons obtain NIH research grants. Of the 2
      identified K08 awards, none led to a subsequent R award. Future research should
      identify barriers to grant procurement to design effective policies to increase
      NIH funding in hand surgery.

PMID- 29363360
TI  - Correction to: Zhang et al., Discovery of novel PDE9A inhibitors with antioxidant
      activities for treatment of Alzheimer's disease.

PMID- 29363359
TI  - Touch Surgery: Analysis and Assessment of Validity of a Hand Surgery Simulation
      "App".
AB  - BACKGROUND: Surgical educators are increasingly exploring surgical simulation and
      other nonclinical teaching adjuncts in the education of trainees. The simulators
      range from purpose-built machines to inexpensive smartphone or tablet-based
      applications (apps). This study evaluates a free surgery module from one such
      app, Touch Surgery, in an effort to evaluate its validity and usefulness in
      training for hand surgery procedures across varied levels of surgical experience.
      METHODS: Participants were divided into 3 cohorts: fellowship-trained hand
      surgeons, orthopedic surgery residents, and medical students. Participants were
      trained in the use of the Touch Surgery app. Each participant completed the
      Carpal Tunnel Release module 3 times, and participants' score was recorded for
      each trial. Participants also completed a customized Likert survey regarding
      their opinions on the usefulness and accuracy of the app. Statistical analysis
      using a 2-tailed t test and analysis of variance was performed to evaluate for
      performance within and between cohorts. RESULTS: All cohorts performed better on
      average with each subsequent simulation attempt. For all attempts, the experts
      outperformed the novice and intermediate participants, while the intermediate
      cohort outperformed the novice cohort. Novice users consistently gave the app
      better scores for usefulness as a training tool, and demonstrated more
      willingness to use the product. CONCLUSIONS: The study confirms app validity and
      usefulness by demonstrating that every cohort's simulator performance improved
      with consecutive use, and participants with higher levels of training performed
      better. Also, user confidence in this app's veracity and utility increased with
      lower levels of training experience.

PMID- 29363361
TI  - Influence of the oral status on cardiovascular diseases in an older Italian
      population.
AB  - Oral diseases have been adversely associated with cardiovascular diseases (CVD),
      which are also the most frequent cause of death in older population. The aim of
      this study was to investigate the association among oral status indexes and CVD
      in patients aged more than 65 years attending in the Oral department of a public
      hospital Policlinico Umberto 1 of Rome. The study population consisted of 533
      patients. Dental status was detected measuring the Decayed, Missing, and Filled
      Teeth (DMFT) and Community Periodontal Index (CPI) indexes. The chi-square test
      with a 95% confidence level was used to assess qualitative variables. Odds ratios
      (ORs) and stepwise logistic regression were used to calculate risk estimates; the
      independent variables: age, gender, DMFT, CPI index, Geriatric Oral Health
      Assessment Index (GOHAI) score, and tooth loss were included in the statistical
      model. P value <0.05 was considered a statistically significant cut-off. No
      differences were found between females and males for DMFT and CPI. GOHAI data
      were worst for females. Patients with CVD had less education and oral care ( P <
      0.05), and higher CPI index and number of missing teeth ( P < 0.05). Data show
      that patients with more than 18 missing teeth have 2.5 times greater risk of CVD.
      CVDs are associated with type 2 diabetes mellitus, underweight, and obesity ( P <
      0.05). From the findings of this study, it can be confirmed a significant link
      between CVD and oral health. A cooperation among geriatrician, cardiologist, and
      dentist is suitable to counteract the development of CVD and to early identify
      patients at risk of CVD.

PMID- 29363362
TI  - Sleep disordered breathing in pregnant women: maternal and fetal risk, treatment
      considerations, and future perspectives.
AB  - INTRODUCTION: Numerous physiologic and anatomic changes during pregnancy
      exacerbate or unmask obstructive sleep apnea in women. Left untreated, upper
      airway flow limitation during pregnancy may lead to dire maternal and fetal
      health consequences. Areas covered: This review outlines the relationship between
      sleep disordered breathing (SDB) and gestational hypertension, preeclampsia, and
      gestational diabetes. It also discusses the implications of SDB on fetal and
      maternal health and concludes with a review of the emerging literature of
      treatment options for SDB in pregnancy and its benefit. Expert commentary:
      Providers should screen, recognize, and treat SDB in pregnant women given its
      implicated risk on maternal and fetal health. This is particularly true in
      preeclampsia, a leading cause of maternal and fetal morbidity and mortality where
      SDB has been shown to add risk and severity. It is important to note that
      repetitive upper airway flow limitations in pregnancy are associated with surges
      in nocturnal blood pressure and poor maternal and fetal outcomes, and may be just
      as detrimental as frank apneas/hypopneas. Future large, prospective, randomized
      controlled studies on the effects of CPAP are still needed. The epidemiology of
      SDB in pregnant women needs to be further studied, as well as highlighting the
      need for systematic, long-term follow ups on mother and infant health post
      delivery.

PMID- 29363363
TI  - Nivolumab for the treatment of urothelial cancers.
AB  - INTRODUCTION: Advanced urothelial cancer patients had limited therapeutic options
      following failure of platinum-based chemotherapy. The recognition that anti
      PD1/PDL1 immune checkpoint inhibitors lead to dramatic and durable responses in a
      subset of patients has transformed the therapeutic landscape of these cancers.
      Since May 2016, five agents targeting this pathway have been approved by the US
      FDA, including the PD-1 inhibitor nivolumab. Areas covered: The purpose of this
      paper was to review the safety, activity and efficacy of nivolumab, an anti-PD1
      checkpoint inhibitor for the treatment of locally-advanced or metastatic
      urothelial cancers. Future therapeutic perspectives were also discussed. Expert
      commentary: Nivolumab is one of five anti-PD1/PDL1 checkpoint inhibitors approved
      for treatment of advanced urothelial cancers. While durable responses can be
      observed, only 15 - 24% of patients are likely to respond. To date, there are no
      validated biomarkers, including PDL1 expression, which might accurately identify
      patients who are likely to respond. Many different biomarkers are currently under
      active investigation. Future direction for therapeutic development is likely to
      involve combination therapies with PD1/PDL1 agent as the therapeutic backbone.

PMID- 29363364
TI  - Insights into biological activity of ureidoamides with primaquine and amino acid
      moieties.
AB  - Primaquine (PQ) ureidoamides 5a-f were screened for antimicrobial, biofilm
      eradication and antioxidative activities. Susceptibility of the tested microbial
      species towards tested compounds showed species- and compound-dependent activity.
      N-(diphenylmethyl)-2-[({4-[(6-methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]
      4-methylpentanamide (5a) and 2-(4-chlorophenyl)-N-(diphenylmethyl)-2-[({4-[(6
      methoxyquinolin-8-yl)amino]pentyl}carbamoyl)amino]acetamide (5d) showed
      antibacterial activity against S. aureus strains (MIC = 6.5 ug/ml). Further,
      compounds 5c and 5d had weak antibacterial activity against Escherichia coli and
      Pseudomonas aeruginosa. None of the tested compounds showed a wide spectrum of
      antifungal activity. In contrast, most of the compounds exerted strong activity
      in a biofilm eradication assay against E. coli, P. aeruginosa and Candida
      albicans, comparable to or even higher than gentamycin, amphotericin B or parent
      PQ. The most active compounds were 5a and 5b. Tested compounds were inactive
      against biofilm formation by C. parapsylosis, Enterococcus faecalis, C.
      tropicalis and C. krusei. Compounds 5b-f significantly inhibited lipid
      peroxidation (80-99%), whereas compound 5c presented interesting LOX inhibition.

PMID- 29363365
TI  - A comparative analysis of immunogenicity and safety of an enterovirus 71 vaccine
      between children aged 3-5 years and infants aged 6-35 months.
AB  - BACKGROUND: The Sinovac enterovirus 71 (EV71) vaccine has shown good safety,
      immunogenicity, and efficacy in infants aged 6-35 months, whom are considered as
      the priority of the target population. However, 3-5 years old children accounted
      for approximately 30% of HFMD cases and are also worth our attention. METHODS: A
      randomized, double-blind, placebo-controlled, batch-to-batch consistency clinical
      trial enrolling 1400 participants aged 6-59 months was performed. We pooled the
      participants receiving three batches of EV71 vaccine together and then stratified
      them into the 6-35 months and 3-5 years. The non-inferiority analysis of the
      geometric mean titer (GMT) of EV71 neutralizing antibody post-vaccination was the
      primary endpoint. RESULTS: In the vaccine group, the GMT of 242 children aged 3-5
      years was 132.72 (95% CI, 110.3-159.6), which was non-inferior to that generated
      in 717 infants aged 6-35 months. Following the vaccination, the incidence of
      adverse reactions was less frequent in children aged 3-5 years (47.0%) than that
      found in infants aged 6-35 months (60.1%) (p = 0.0026). CONCLUSIONS: Our study
      indicated that the EV71 vaccine was also safe in children aged 3-5 years, with
      non-inferior immunogenicity to that in infants aged 6-35 months.

PMID- 29363366
TI  - Anaemia and depletion of iron stores as risk factors for postpartum depression: a
      literature review.
AB  - PURPOSE: Iron-deficiency and anaemia are common in pregnant and postpartum women
      because of increasing iron demand and blood loss. Many women also enter pregnancy
      with pre-depleted iron stores. We reviewed the evidence linking anaemia and/or
      iron-deficiency to postpartum depression (PPD). METHODS: We identified seventeen
      studies in four databases including randomized-controlled trials (RCTs) and
      observational studies assessing the impact of anaemia, iron-deficiency and iron
      supplementation on the risk of PPD. We extracted data on sample size,
      geographical region, obstetrical complications, measures of depression,
      haemoglobin, iron levels and intake of iron supplementation and critically
      appraised the results from the studies. RESULTS: Eight out of ten studies found
      higher risk for PPD (r - 0.19 to -0.43 and ORs 1.70-4.64) in anaemic women. Low
      ferritin in the postpartum period but not during pregnancy was associated with
      increased risk of PPD. Iron supplementation in the postpartum period decreased
      risk of PPD in four out of five studies, whereas it did not protect from PPD if
      given during pregnancy. Limitations include study heterogeneity, discrepancy of
      prevalence of PPD and usage of a screening tool for evaluation of PPD.
      CONCLUSION: Anaemia and/or iron-deficiency may contribute to PPD in at-risk
      women. Further studies should elucidate the association between these entities.

PMID- 29363367
TI  - The association between Mullerian anomalies and IUGR: a meta-analysis.
AB  - BACKGROUND: Published literature regarding the association between Mullerian
      anomalies and intrauterine growth restriction (IUGR) is controversial. To date,
      no meta-analysis has been performed for assessing the relationship between the
      Mullerian anomalies and IUGR. Therefore, the aim of this study was to perform a
      meta-analysis by combining data from relevant studies to assessing the
      association of between Mullerian anomalies and IUGR. METHODS: A systematic search
      was conducted in PubMed, Scopus and Web of Science to identify of all studies
      prior to September 2017. Egger's and Begg's tests were carried out to
      quantitatively assess publication bias. To estimate the heterogeneity among
      studies the Q-statistic test and I-squared (I2) test were used. The random
      effects model was conducted to obtain pooled odds ratio (OR) as a measure of the
      association between Mullerian anomalies and IUGR. RESULTS: A total of seven
      studies were included in this meta-analysis with a sample of 605,005
      participants. The pooled overall OR was 1.93 (95% CI: 1.52, 2.34). CONCLUSIONS:
      We reported that mullerian anomalies are a risk factor for IUGR. However, further
      evidence by larger prospective cohort studies is needed to make conclusive
      evidence regarding the association between mullerian anomalies and IUGR.

PMID- 29363369
TI  - Combined therapy with epidermal growth factor receptor tyrosine kinase inhibitors
      for non-small cell lung cancer.
AB  - INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      (TKIs) have a pronounced clinical benefit for patients with advanced non-small
      cell lung cancer (NSCLC) positive for EGFR activating mutations. Such individuals
      inevitably develop resistance to these drugs, however, new treatment strategies
      to overcome such resistance are being actively pursued. The clinical benefit of
      EGFR-TKIs for patients with locally advanced NSCLC remains to be clarified. Areas
      covered: This review summarizes the recent progress in combination treatment with
      EGFR-TKIs and either chemotherapy or radiotherapy for patients with NSCLC
      positive for EGFR activating mutations. Expert commentary: Combination therapy
      with EGFR-TKIs and various other treatment options are under investigation in
      clinical studies. Although early studies failed to show a clinical benefit for
      such combination therapy because of a lack of patient selection, clinical studies
      with patient selection based on EGFR mutation status have shown promising
      results. Such combination therapy might eventually replace the current standard
      treatment for patients with NSCLC positive for EGFR activating mutations.

PMID- 29363368
TI  - Total glucosides of paeony suppresses experimental autoimmune uveitis in
      association with inhibition of Th1 and Th2 cell function in mice.
AB  - Total glucosides of paeony (TGP) are active components extracted from the roots
      of Paeonia lactiflora Pall. In this study, we investigated the role and
      mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The
      C57BL/6 mice were randomly divided into three groups: sham group, EAU-control
      group, and EAU-TGP group. Clinical score of images of the eye fundus were taken
      on 7, 14, 21, and 28 days after induction of EAU. The concentrations of
      proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU
      induction with the use of a multiplex assay system. Flow cytometry was used to
      analyze the frequency of CD4+, CD8+, interferon-gamma (IFN-gamma), and CD4+/CD8+
      ratio in spleen and lymph nodes. Western blotting was used to measure expressions
      of mitogen-activated protein kinase (MAPK) pathway-related proteins in retina.
      Clinical scores for uveitis were lower in TGP-treated EAU mice than those without
      TGP treatment. Importantly, the concentrations of cytokines induced by T-helper 1
      (Th1) and T-helper 2 (Th2) cells in intraocular fluid were reduced in EAU mice
      treated with TGP. Furthermore, the frequency of CD4+, IFN-gamma, and CD4+/CD8+
      ratio was decreased and the frequency of CD8+ was increased in spleen and lymph
      nodes of mice treated with TGP. The anti-inflammatory effects of TGP were
      mediated by inhibiting the MAPK signaling pathways. Our results showed that TGP
      suppressed uveitis in mice via the inhibition of Th1 and Th2 cell function. Thus,
      TGP may be a promising therapeutic strategy for uveitis, as well as other ocular
      inflammatory diseases.

PMID- 29363370
TI  - Sulfonamide inhibition studies of two beta-carbonic anhydrases from the
      ascomycete fungus Sordaria macrospora, CAS1 and CAS2.
AB  - The two beta-carbonic anhydrases (CAs, EC 4.2.1.1) recently cloned and purified
      from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2, were investigated
      for their inhibition with a panel of 39 aromatic, heterocyclic, and aliphatic
      sulfonamides and one sulfamate, many of which are clinically used agents. CAS1
      was efficiently inhibited by tosylamide, 3-fluorosulfanilamide, and 3
      chlorosulfanilamide (KIs in the range of 43.2-79.6 nM), whereas acetazolamide,
      methazolamide, topiramate, ethoxzolamide, dorzolamide, and brinzolamide were
      medium potency inhibitors (KIs in the range of 360-445 nM). CAS2 was less
      sensitive to sulfonamide inhibitors. The best CAS2 inhibitors were 5-amino-1,3,4
      thiadiazole-2-sulfonamide (the deacetylated acetazolamide precursor) and 4
      hydroxymethyl-benzenesulfonamide, with KIs in the range of 48.1-92.5 nM.
      Acetazolamide, dorzolamide, ethoxzolamide, topiramate, sulpiride, indisulam,
      celecoxib, and sulthiame were medium potency CAS2 inhibitors (KIs of 143-857 nM).
      Many other sulfonamides showed affinities in the high micromolar range or were
      ineffective as CAS1/2 inhibitors. Small changes in the structure of the inhibitor
      led to important differences of the activity. As these enzymes may show
      applications for the removal of anthropically generated polluting gases, finding
      modulators of their activity may be crucial for designing environmental-friendly
      CO2 capture processes.

PMID- 29363371
TI  - The impact of cerclage in twin pregnancies on preterm birth rate before 32 weeks.
AB  - PURPOSE: To evaluate whether cerclage in twins reduces the rate of spontaneous
      preterm birth <32 weeks when compared to expectant management. METHODS: This is a
      retrospective cohort study of twin pregnancies with the following indications for
      cerclage from two institutions: history of prior preterm birth, ultrasound
      identified short cervix <=2.5 cm, and cervical dilation >=1.0 cm. The "cerclage"
      cohort received a cerclage from a single provider at a single institution from
      2003-2016. The "no cerclage" group included all patients with similar indications
      that were expectantly managed from 2010-2015, at a second institution where
      cerclages are routinely not performed in twin pregnancies. The primary outcome
      was the rate of spontaneous preterm birth at <32 weeks. Secondary outcomes were
      the rates of spontaneous and overall (including medically indicated) preterm
      births at <32 weeks, < 34 weeks, and <36 weeks, chorioamnionitis, birth weight,
      and neonatal mortality within 30 days of life. We also performed a planned
      subgroup analysis stratified by cerclage indication. RESULTS: In all, 135 women
      were included in two cohorts: cerclage (n = 96) or no cerclage (n = 39). The
      rates of spontaneous preterm birth <32 weeks were 10.4% (n = 10) with cerclage
      versus 28.2% (n = 11) without cerclage (OR 0.23, CI 0.08-0.70, p = .017). After
      adjusting for cerclage indication, clinical history, age, chorionicity, insurance
      type, race, BMI, in-vitro fertilization, and multifetal reduction, there remained
      a significant reduction in the cerclage group of spontaneous preterm birth <32
      weeks (adjusted odds ratio (aOR) 0.24, CI 0.06-0.90, p = .035), spontaneous
      preterm birth <36 weeks (aOR 0.34, CI 0.04-0.81, p = .013) as well as in overall
      preterm birth <32 weeks (aOR 0.31, CI 0.1-0.86, p = .018), and overall preterm
      birth <36 weeks (aOR 0.37, CI 0.10-0.84, p = .030). When stratified by short
      cervix or cervical dilation in the cerclage versus no cerclage groups, there was
      a significant decrease in spontaneous preterm birth <32 weeks in the cerclage
      group with cervical dilation (11.1 versus 41.2%, p = .01) but not in the cerclage
      group with short cervix only, even for cervical length <1.5 cm. Pregnancy latency
      was 91 days in the cerclage group versus 57 days in the no cerclage group (p =
      .001), with a median gestational age at delivery of 35 versus 32 weeks (p =
      .002). There was no increase in chorioamnionitis in the cerclage group.
      Furthermore, there was a significant increase in birth weight (median 2278 versus
      1665 g, p < .001) and decrease in perinatal death <30 days (1.6 versus 12.9%, p =
      .001). CONCLUSIONS: Cerclage in twin pregnancies significantly decreased the rate
      of spontaneous preterm birth <32 weeks compared to expectant management. However,
      when stratified by cerclage indication, this decrease in primary outcome only
      remained significant in the group with cervical dilation.

PMID- 29363372
TI  - Synthesis, biological activity and molecular modelling studies of shikimic acid
      derivatives as inhibitors of the shikimate dehydrogenase enzyme of Escherichia
      coli.
AB  - Shikimic acid (SA) pathway is the common route used by bacteria, plants, fungi,
      algae, and certain Apicomplexa parasites for the biosynthesis of aromatic amino
      acids and other secondary metabolites. As this essential pathway is absent in
      mammals designing inhibitors against implied enzymes may lead to the development
      of antimicrobial and herbicidal agents harmless to humans. Shikimate
      dehydrogenase (SDH) is the fourth enzyme of the SA pathway. In this contribution,
      a series of SA amide derivatives were synthesised and evaluated for in vitro SDH
      inhibition and antibacterial activity against Escherichia coli. All tested
      compounds showed to be mixed type inhibitors; diamide derivatives displayed more
      inhibitory activity than synthesised monoamides. Among the evaluated compounds,
      molecules called 4a and 4b were the most active derivatives with IC50 588 and 589
      uM, respectively. Molecular modelling studies suggested two different binding
      modes of monoamide and diamide derivatives to the SDH enzyme of E. coli.

PMID- 29363373
TI  - Double-blind randomized placebo-controlled trial to evaluate the efficacy and
      safety of short-course low-dose oral prednisolone in pityriasis rosea.
AB  - PURPOSE: To evaluate the efficacy and safety of short-course low-dose oral
      prednisolone in symptomatic pityriasis rosea (PR) of onset <5 days and compare it
      with placebo. MATERIAL AND METHODS: Placebo-controlled randomized double-blind
      study design with the treatment group receiving tapering doses of oral
      prednisolone over 2 weeks and the control group receiving a placebo. Outcome
      measures evaluated were subsidence of patient-perceived pruritus, improvement in
      rash quantified by a specific score, adverse effects and relapse at 12 weeks.
      RESULTS: The improvement in the pruritus score as well as objective rash score
      were much better in the prednisolone-treated group. No adverse effects reported
      in either group. The relapse rate at 12 weeks was much higher in the prednisolone
      treated group. CONCLUSIONS: Oral corticosteroids, even if used in low-dose and
      for a short tapering course should not be the first line of therapy for PR. The
      only justified indication may be extensive and highly symptomatic lesions of PR.

PMID- 29363374
TI  - Mood state at the beginning of the pregnancy and its influence on obstetric and
      perinatal outcomes.
AB  - AIM: We designed this study to ascertain the prevalence of depressive disorders
      and anxiety at the beginning of the pregnancy, studying possible associated
      factors and assessing the influence of mood disorders on perinatal outcomes.
      METHODS: A representative sample of 191 pregnant women at first trimester of
      their pregnancies completed a questionnaire that included the Whooley's
      questions, the Spanish version of the Beck Depression Inventory (BDI), the State
      Trait Anxiety Inventory and a series of questions related to health status,
      general mood and sociodemographic variables. Later, we prospectively evaluated
      the influence of anxiety and depression on the perinatal and obstetric results in
      145 of them. RESULTS: More than 20% of pregnant women presented high levels of
      anxiety. The mean values of the state and trait anxiety scores were 38.7 (SD 9.8)
      and 34.5 (SD 9.5). The mean BDI score was 5.97 (SD 4.9), with 9.5% of
      participants achieving scores compatible with depression, (61% mild in, 22.2%
      moderate, and 16.6% severe). BDI scores were significantly lower in women who
      became pregnant after assisted reproductive techniques. We observed an
      association between depression and trait anxiety scores with an infant's low
      birth weight. The multivariate analysis showed that the feeling of happiness at
      the beginning of pregnancy was the best predictor of foetal weight. CONCLUSION:
      The prevalence of emotional disorders in the first trimester of pregnancy is
      high, with more than 20% of pregnant women presenting high levels of anxiety, and
      more than 9.5% presenting depression. During the first trimester, depression and
      anxiety were associated with low birth weight.

PMID- 29363376
TI  - Neuroleptic malignant syndrome in pregnancy: case report and literature review.
AB  - BACKGROUND: Neuroleptic malignant syndrome (NMS) is a serious complication
      associated with the use of drugs that affect dopaminergic system
      neurotransmission. The occurrence of NMS during pregnancy or gestation is
      considered a life-threatening obstetric emergency. CASE: We are reporting the
      first case in Latin America of NMS in one pregnant women with acute psychotic
      episode. One day after starting with antipsychotic therapy, she developed a fever
      higher than 39.0  degrees C with tachycardia, tachypnea, generalized muscle
      rigidity and somnolence, with creatine kinase (CPK) levels evidencing a result of
      2800 U/L. She was treated successfully with levetiracetam, biperiden and
      quetiapine. DISCUSSION: A search in PubMed, Embase and Ovid from 1988 to 2016
      resulted in seven cases reported in either pregnant or puerperal women. In
      general, NMS resolves within 3-14 days; most NMS cases reported during pregnancy
      have involved the use of haloperidol (5 case reports) which is concordant with
      this report. The obstetric results were good in cases reported, only two women
      showed signs, among them: hyperemesis gravidarum and preterm delivery. Most of
      the pregnant women who had NMS presented other associated comorbidities, being
      mostly of infectious origin. In other investigations, it has been affirmed that
      NMS can become lethal in adults; however, in our search for pregnant women with
      this disease, no associated mortality was found. CONCLUSIONS: NMS is seen
      infrequently during pregnancy. The clinical diagnosis requires high suspicion by
      the examiner. It is important that obstetricians timely recognize the condition.

PMID- 29363375
TI  - Sodium butyrate has anti-proliferative, pro-differentiating, and immunomodulatory
      effects in osteosarcoma cells and counteracts the TNFalpha-induced low-grade
      inflammation.
AB  - Butyrate, an essential factor for colonocytes and regulator in the development of
      colon cancer, is partially absorbed by the gut. It influences the proliferation
      and differentiation of several cell types including osteoblasts. We evaluated the
      effects of different doses of butyrate on differentiation and functionality of
      osteosarcoma cells in vitro and the expression of a pro-inflammatory phenotype in
      a normal or inflammatory environment. SaOS-2 osteosarcoma cells were induced to
      differentiate and contemporarily treated for 24 h, 48 h, or 7 days with sodium
      butyrate 10-4, 5 * 10-4, or 10-3 M in the presence or absence of tumor necrosis
      factor alpha (TNFalpha) 1 ng/mL, a pro-inflammatory stimulus. Despite the mild
      effects on proliferation and alkaline phosphatase activity, butyrate dose- and
      time-dependently induced the expression of a differentiated phenotype (RUNX2,
      COL1A1 gene expression, and osteopontin gene and protein expression). This was
      associated with a partial inhibition of nuclear factor kappa B (NF-kappaB)
      activation and the induction of histone deacetylase 1 expression. The net effect
      was the expression of an anti-inflammatory phenotype and the increase in the
      osteoprotegerin-to-receptor activator of nuclear factor kappa-B ligand (RANKL)
      ratio. Moreover, butyrate, especially at the highest dose, counteracted the
      effects of the pro-inflammatory stimulus of TNFalpha 1 ng/mL. Butyrate affects
      osteosarcoma cell metabolism by anticipating the expression of a differentiated
      phenotype and by inducing the expression of anti-inflammatory mediators.

PMID- 29363377
TI  - Liver transplantation for hepatic alveolar echinococcosis: literature review and
      three new cases.
AB  - BACKGROUND: Echinococcosis is a helminthic infection caused by ingestion of the
      eggs of the parasitic metacestode of one of four members of the Echinococcus
      genus. Among them, hepatic alveolar echinococcosis (HAE) mimics slow growing
      liver tumour with subsequent invasion to liver tissues and metastatic
      dissemination. Liver transplantation (LT) remains as the only treatment option
      when the lesions exceed the resectability limits. We described the first three
      cases of HAE who underwent orthotopic LT in Iran. A literature review was also
      conducted to summarize experiences of different transplant centres around the
      world. METHODS: PubMed, Scopus and Web of Science databases were searched up to
      April 2017 using keywords related to echinococcosis, liver and transplantation.
      RESULTS: Including this case report, a total of 150 patients underwent LT due to
      echinococcosis from 1994 to 2017. The mean age at LT was 38 years (range: 12-71)
      and 51% were male. About 95% of the transplantations were performed due to HAE.
      Pre- and post-transplant benzimidazole therapy was considered in 69% and 73% of
      patients, respectively. Recurrence rate varied between 0% and 60%. The overall 1
      , 5- and 10-year survival rates were 60-100%, 67-85% and 49-75%, respectively.
      CONCLUSIONS: LT combined with pre- and post-transplant benzimidazole therapy
      appears to be feasible and effective for patients with fatal HAE.

PMID- 29363379
TI  - Acute exacerbations after decades of non-active chronic multiple sclerosis.

PMID- 29363378
TI  - Downregulation of SIRT6 is associated with poor prognosis in patients with non
      small cell lung cancer.
AB  - Objective To explore the prognostic significance of nicotinamide adenine
      dinucleotide (NAD)-dependent protein deacetylase sirtuin-6 (SIRT6), encoded by
      the sirtuin 6 ( SIRT6) gene, in a population of Chinese Han patients with non
      small cell lung cancer (NSCLC). Methods Cancer tissues and normal lung tissues
      (>5 cm adjacent to cancer tissue) were collected from Chinese Han patients with
      NSCLC. Expression levels of SIRT6 and histone H3-acetyl K56 ( H3K56), in cancer
      and normal lung tissues from patients with NSCLC, were detected by reverse
      transcription polymerase chain reaction, Western blot and immunohistochemistry.
      Correlations between SIRT6 expression and various clinicopathologic features were
      investigated. Results Out of 86 patients included in the study, mRNA and protein
      SIRT6 levels were down-regulated in NSCLC tissue versus normal lung tissue, and
      SIRT6 levels were inversely correlated with H3K56 levels. Positive rates of SIRT6
      were significantly correlated with degree of cell differentiation, TNM stage,
      lymph node metastasis, overall survival and metastasis-free survival. Conclusion
      Downregulation of SIRT6 expression may promote NSCLC malignancy in the Chinese
      Han population. SIRT6 may be a potential therapeutic target in Chinese Han
      patients with NSCLC.

PMID- 29363380
TI  - Twenty years of FISH-based translocation analysis for retrospective ionizing
      radiation biodosimetry.
AB  - PURPOSE: The fluorescent in situ hybridization (FISH) technique, which easily
      detects reciprocal translocations, is currently used to estimate doses in
      retrospective biological dosimetry, after suspected accidental overexposure to
      ionizing radiation (IR). This study of 42 cases aimed to verify the
      appropriateness of this assay for radiation dose reconstruction, compared to the
      dicentric assay, and to evaluate other limitations. MATERIAL AND METHODS: We
      labeled chromosomes 2, 4, and 12 by 3-color FISH painting to detect
      translocations on lymphocytes of patients with suspected past IR overexposure.
      RESULT: Translocation dose estimation showed doses significantly different from 0
      Gy in 25 of the 42 cases. The lowest positive dose measured was 0.3 Gy. Several
      months after IR exposure, the doses measured by translocation and dicentric
      assays are quite similar. For a year, dose estimation by translocation assay
      becomes more relevant as dicentric frequency starts to decrease, coming close to
      0 for more than a year after the exposure. The persistence of translocations
      enabled us to corroborate an overexposure 44 years earlier. Interpretation of the
      observed translocation yield requires the knowledge of the patient's other
      radiation exposures. A dose assessment by this biomarker is relevant only if the
      radiation exposure is confirmed. CONCLUSIONS: This technique is appropriate for
      corroborating a former IR exposure of individuals. When the radiation dose is
      greater than 1 Gy, the translocations in complex exchanges must be considered.
      Another relevant point is the use of an appropriate background yield of
      translocations. The dose assessment, however, also depends on exposure to various
      genotoxic agents besides IR. If no evidence about the existence of radiation
      exposure is available, dose assessment is not useful. For this reason, report
      only the translocation frequency and its comparison with the background yield by
      age class is preferable.

PMID- 29363381
TI  - Clinical outcomes of magnetic activated sperm sorting in infertile men candidate
      for ICSI.
AB  - Magnetic activated cell sorting (MACS) with annexin V microbeads deselected
      apoptotic sperm with externalized phosphatidylserine (PS) residues on their
      surface and decrease chance of such sperm to be inseminated. Therefore, the aim
      of this study was to evaluate efficiency of MACS procedure in a prospective
      randomized trial. Sixty-two semen samples were allocated into two groups and
      processed according to: (i) a combination of MACS with density gradient
      centrifugation (MACS-DGC) as study group (N = 29); and (ii) DGC alone as a
      control group (N = 33). Fertilization, embryo quality, pregnancy and implantation
      rates were compared between the two groups. Although, no significant difference
      was observed in fertilization rates between the two groups, the percentage of
      high-quality embryos, pregnancy and implantation rates was significantly higher
      in the MACS-DGC group compared to DGC alone. Therefore, MACS may help to select
      the most fertile sperm and improve clinical outcomes of intra-cytoplasmic sperm
      injection (ICSI).

PMID- 29363382
TI  - Precise Retrograde Supera Stenting of the Ostium (PRESTO) of the Superficial
      Femoral Artery for Complex Femoropopliteal Occlusions: The PRESTO Technique.
AB  - PURPOSE: To describe a novel technique designed to safely and precisely deploy
      the Supera stent accurately at the ostium of the proximal superficial femoral
      artery (SFA) without compromising the profunda and common femoral arteries.
      TECHNIQUE: After antegrade crossing of the chronic total occlusion (CTO) at the
      SFA ostium and accurate predilation of the entire SFA lesion, a retrograde
      arterial access is obtained. The Supera stent is navigated in retrograde fashion
      to position the first crown to be released just at the SFA ostium. Antegrade
      dilation is performed across the retrograde access site to obtain adequate
      hemostasis. The technique has been applied successfully in 21 patients (mean age
      78.1+/-8.2 years; 13 men) with critical limb ischemia using retrograde Supera
      stenting from the proximal anterior tibial artery (n=6), the posterior tibial
      artery (n=2), retrograde stent puncture in the mid to distal SFA (n=2), the
      native distal SFA/proximal popliteal segment (n=6), and the distal anterior
      tibial artery (n=5). No complications were observed. CONCLUSION: Distal
      retrograde Supera stent passage and reverse deployment allow precise and safe
      Supera stenting at the SFA ostium.

PMID- 29363383
TI  - A forensic evaluation of impalement injuries.
AB  - Impalement injuries transfix a victim in an inescapable or helpless position. A
      study was undertaken at Forensic Science SA from 2002 to 2016 of all impalement
      deaths. There were six vehicle accidents (M:F=5:1; age 14-67 years, average age
      38.5 years) involving impalements with a tree branch ( n=2; groin and chest), a
      metal pipe ( n=2; leg and head), a metal bridge railing (groin) and a metal fence
      post (chest). Two cases (both males, aged 47 and 18 years) had slipped on
      fences/gates, with impalements of the ankle and groin. A case of suicide (male,
      aged 80 years) was impaled through the head on a bolt fixed to the floor. A
      homicide case (male, aged 27 years) involved impalement through the chest by a
      spear from a spear gun. In certain cases (e.g. with anogenital injuries),
      differentiating accidental from inflicted impalement injuries may be difficult.
      In equivocal cases, adequate scene evaluations with photographic documentation
      are required prior to autopsy, ideally with the object available for examination.

PMID- 29363384
TI  - Analysis of dental injuries with clinical implications: A forensic case report.
AB  - Dental injuries, especially of the incisors, caused by punches in violent
      criminal attacks could be seen in daily forensic casework involving the
      identification of injuries to a living body. Sometimes, when there is neither
      circumstantial evidence nor information about the surrounding circumstances, it
      is difficult to discern the cause of these injuries and the manner in which they
      were inflicted. As an example of clinical forensic medicine, we present the case
      of a 58-year-old woman whose teeth were injured when fighting with her son-in-law
      over household affairs with no witnesses present. The two parties had conflicting
      stories about the cause of the woman's injury. The woman claimed that her teeth
      were lost while she was being beaten by her son-in-law, and the man argued that
      the damage to his mother-in-law's teeth was self-inflicted when she bit his
      fingers. The police attending the crime called for a forensic examination.
      Forensic practitioners analysed the mechanism of the tooth loss using multi-slice
      spiral computed tomography (MSCT) and imaging reconstruction technology. Local
      alveolar bone (medial alveolar) fracture and a small area of alveolar bone loss
      were found on MSCT. Thus, forensic medical experts speculated that the woman's
      lower central and lateral incisors were lost as a result of a violent attack and
      were not self-inflicted. Finally, forensic practitioners helped police in
      avoiding a miscarriage of justice and wrongful conviction.

PMID- 29363385
TI  - Longitudinal personality change associated with cognitive decline in multiple
      sclerosis.
AB  - We previously reported that personality and cognition were stable over 3 years in
      patients with multiple sclerosis (MS). This study examined whether a longer
      duration would reveal evidence of emerging personality dysfunction. The NEO Five
      Factor Inventory and Brief International Cognitive Assessment for MS was used to
      assess personality and cognition, respectively. Patients were classified as "Cog
      Stable" or "Cog Decline" based on cognitive deterioration over 5 years.
      Extraversion and Conscientiousness declined across pooled groups. Follow-up of a
      group by time interaction found that decline in these traits was more evident in
      the Cog Decline group, demonstrating a link between personality and cognitive
      change.

PMID- 29363386
TI  - Increased psoriasis frequency in patients with familial Mediterranean fever.
AB  - OBJECTIVE: Familial Mediterranean fever (FMF) is a periodic fever syndrome caused
      by MEFV mutations. FMF may be associated with psoriasis in some cases. The
      prevalence of psoriasis in the normal Turkish population is 0.42%. We aimed to
      investigate the prevalence of psoriasis among FMF patients and their relatives.
      METHODS: FMF patients followed at Hacettepe University Adult and Pediatric
      Rheumatology Departments between January and August 2016 were included. FMF
      patients/their relatives were accepted to have psoriasis if the diagnosis was
      made by a dermatologist. RESULTS: A total of 351 FMF patients (177 adults; 174
      children) were included. The median (min-max) age of adult and pediatric patients
      was 35 (19-63) and 10 (2-18) years, respectively. Thirteen (3.7%) FMF patients
      (11 adults, 2 children) had psoriasis. Psoriasis was more common in adult than
      pediatric patients (p = 0.02). Psoriasis was present in 22 (12.4%) of adult and 9
      (5.2%) of pediatric patients' relatives (p = 0.023). The frequency of psoriasis
      in >=1 relatives of FMF patients was found to be 8.8%. Abdominal pain and fever
      were significantly higher, and arthralgia, arthritis, pleural chest pain, and
      pericarditis were significantly less frequent in the pediatric group than in
      adults (p < 0.05). CONCLUSION: Psoriasis was more common in FMF patients than in
      the normal population. Thus, FMF patients should be questioned and carefully
      examined for psoriasis lesions and psoriasis family history. Prospective
      multicenter studies may be important to find the incidence of psoriasis in FMF.

PMID- 29363387
TI  - Association between ABO blood types and pain perception.
AB  - AIM OF THE STUDY: Pain perception is associated with different phenotypic
      characteristics such as sex, eye, and hair color. Hence, it is assumed that ABO
      blood type can also affect pain perception. MATERIALS AND METHODS: In order to
      investigate this hypothesis, an experimental study with healthy volunteers (18-40
      years) was designed. The experimental procedure included a blood type test and
      two rounds of pressure pain threshold assessments separated by a cold pressor
      test. Pressure pain threshold was assessed bilaterally at the temporalis,
      masseter, and deltoid muscles, where the muscle sites were randomized. Cold
      pressor test was conducted by immersion of participants' non-dominant hand into
      iced water of 1-4  degrees C for 2 min. RESULTS: Thirty-seven healthy volunteers,
      distributed in the four blood type groups, completed the study. Participants with
      blood type B scored the highest pressure pain thresholds at the examined
      craniofacial muscles, while participants with blood type AB tended to score the
      lowest. Furthermore, participants with blood type AB displayed the highest
      elevation in pressure pain thresholds after cold pressor test. CONCLUSIONS:
      Participants with blood type B displayed the lowest mechanical pain sensitivity
      and the blood type AB group exhibited the strongest conditioned pain modulation
      effect. These findings emphasize the necessity of considering ABO blood types in
      future pain research.

PMID- 29363388
TI  - Gender Differences in Hospital CEO Compensation: A National Investigation of Not
      for-Profit Hospitals.
AB  - Gender pay equity is a desirable social value and an important strategy to fill
      every organizational stratum with gender-diverse talent to fulfill an
      organization's goals and mission. This study used national, large-sample data to
      examine gender difference in CEO compensation among not-for-profit hospitals.
      Results showed the average unadjusted annual compensation for female CEOs in 2009
      was $425,085 compared with $581,121 for male CEOs. With few exceptions, the
      difference existed across all types of not-for-profit hospitals. After
      controlling for hospital- and area-level characteristics, female CEOs of not-for
      profit hospitals earned 22.6% less than male CEOs of not-for-profit hospitals.
      This translates into an earnings differential of $132,652 associated with gender.
      Explanations and implications of the results are discussed.

PMID- 29363390
TI  - Correction to: Lenihan, et al., MDRD-Estimated GFR at One Year Post-Renal
      Transplant is a Predictor of Long-Term Graft Function.

PMID- 29363389
TI  - Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant
      Expenditures in Hemophilia B Patients Receiving Standard Half-Life Versus
      Extended Half-Life Products and Those Switching from Standard Half-Life to
      Extended Half-Life Products.
AB  - BACKGROUND: Hemophilia B requires replacement therapy with factor IX (FIX)
      coagulation products to treat and prevent bleeding episodes. A recently
      introduced extended half-life (EHL) recombinant FIX replacement product provided
      the opportunity to compare the amount of dispensed factor and expenditures for
      EHL treatment compared with a standard half-life (SHL) product. OBJECTIVE: To
      determine factor international units (IUs) dispensed and expenditures associated
      with switching from nonacog alfa, the most commonly used SHL replacement product,
      to eftrenonacog alfa, an EHL FIX replacement product. METHODS: Two U.S. claims
      databases were analyzed. A large national specialty pharmacy dispensation claims
      database was used to identify the number of IUs dispensed and monthly charges for
      all patients with hemophilia B from April 2015 to June 2016. Truven Health
      MarketScan Research Databases (January 2010-July 2016) were used to identify IUs
      and expenditures for patients with claims data for at least 3 months before and
      after switching from the SHL to the EHL product. Medians for IUs and expenditures
      are presented to accommodate for skewness of data distribution. RESULTS: The
      national specialty pharmacy database analysis included 296 patients with moderate
      or severe hemophilia B (233 on SHL; 94 on EHL). Median monthly factor dispensed
      was 11% lower (2,142 IU) in the EHL versus SHL cohort over the study period,
      while individual monthly reductions ranged from 32% to 47% (9,838 IU to 16,514
      IU). Using the wholesale acquisition cost, the median per-patient monthly factor
      expenditures over the 15-month study period were 94% higher ($23,005) for the EHL
      than for the SHL product. Individual median monthly expenditure differences
      ranged from 15% ($6,562) to 49% ($19,624). In the Truven database, 14 patients
      switched from the SHL to the EHL product. The amount of factor dispensed was
      variable; in the 1-year period before and after the switch from the SHL to the
      EHL product, mean IUs dispensed decreased by 3,005 IU, while median IUs dispensed
      increased by 4,775 IU. Factor replacement expenditures were higher after
      switching from the SHL to the EHL product in each of the 3-month periods examined
      before versus after the switch. CONCLUSIONS: This analysis of real-world data
      showed that switching from the SHL to the EHL product was associated with higher
      expenditures. Increased expenditures noted in the first 3 months after switching
      may be related to initial stocking up of the EHL product, but expenditures were
      sustained throughout the 1-year period of data analysis. Further analysis of
      these findings with larger numbers of patients should be explored. DISCLOSURES:
      This study was sponsored by Pfizer. Pfizer employees were involved in the study
      design; the collection, analysis, and interpretation of data; the review of the
      manuscript; and the decision to submit for publication. All authors are employees
      of Pfizer. No author received an honorarium or other form of payment related to
      the development of this manuscript. All authors participated in the study design,
      data interpretation, and manuscript review and revisions and granted approval for
      the submission of the manuscript. Alvir, McDonald, and Tortella also participated
      in data analysis. Data from this paper were presented in part at the European
      Association for Haemophilia and Allied Disorders Annual Meeting, February 1-3,
      2017, Paris, France; at the International Society for Pharmacoeconomics and
      Outcomes Research Annual Meeting, May 20-24, 2017, Boston, MA; and at the
      International Society on Thrombosis and Haemostasis Congress, July 8-13, 2017,
      Berlin, Germany.

PMID- 29363391
TI  - BRAG1/IQSEC2 as a regulator of small GTPase-dependent trafficking.
AB  - Precise trafficking events, such as those that underlie synaptic transmission and
      plasticity, require complex regulation. G-protein signaling plays an essential
      role in the regulation of membrane and protein trafficking. However, it is not
      well understood how small GTPases and their regulatory proteins coordinate such
      specific events. Our recent publication focused on a highly abundant synaptic
      GEF, BRAG1, whose physiologic relevance was unknown. We find that BRAG1s GEF
      activity is required for activity-dependent trafficking of AMPARs. Moreover,
      BRAG1 bidirectionally regulates synaptic transmission in a manner independent of
      this activity. In addition to the GEF domain, BRAG1 contains several functional
      domains whose roles are not yet understood but may mediate protein-protein
      interactions and regulatory effects necessary for its role in regulation of AMPAR
      trafficking. In this commentary, we explore the potential for BRAG1 to provide
      specificity of small GTPase signaling, coordinating activity-dependent activation
      of small GTPase activity with signaling and scaffolding molecules involved in
      trafficking through its GEF activity and other functional domains.

PMID- 29363393
TI  - Safety Climate Among Nontraditional Workers in Construction: Arguing for a Focus
      on Construed External Safety Image.
AB  - Safety climate, employees' perceptions of work-related safety, 1 has been
      promoted as a leading indicator of workplace safety in construction. 2 , 3 While
      research has primarily examined internal organizational sources (e.g., manager
      attitudes, formal organizational policies) on these perceptions, external sources
      of information might be more relevant to construction workers in nontraditional
      jobs who work for a limited time and/or have limited interaction with other
      employees. This paper argues for the future development of a construed external
      safety image scale to measure employees' perceptions about how external groups
      view their organization's safety. 4 The construed external safety image would
      capture the external sources that nontraditional workers use to assess safety
      climate and will allow public health researchers to identify and change dangerous
      workplaces while more effectively communicating information about safe workplaces
      to workers. The public health relevance of safety climate and construed external
      safety image for monitoring and communicating safety to nontraditional workers
      require examination.

PMID- 29363392
TI  - Evaluation of health-related quality of life in hemolytic uraemic syndrome
      patients treated with eculizumab: a systematic evaluation on basis of EMPRO.
AB  - BACKGROUND: Hemolytic uraemic syndrome (HUS) is progressive renal failure disease
      and determination of their quality of life (QoL) on the basis of patient-reported
      outcomes (PROs) are becoming increasingly important in the economic evaluations
      for its treatment with eculizumab (ECU). AIM: To perform the systematic
      evaluation of QoL in HUS patients treated with ECU on the basis of Evaluating
      Measures of Patient Reported Outcomes (EMPRO) tool. MATERIALS AND METHODS: A
      systematic review was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL
      and Google Scholar till September 2016 by two independent researchers. Each
      identified instrument was evaluated for its quality of performance by using the
      EMPRO tool for its overall score and seven attribute specific scores (range 0
      100, worst to best). RESULTS: Five different PROs instruments were identified
      from 10 articles (n = 112) which showed eculizumab significantly improves health
      related quality of life (HRQOL) in atypical HUS (aHUS) patients. Amongst five
      instruments viz. EuroQol five dimensions questionnaire (EQ-5 D), Functional
      Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Headache Impact Test-6
      (HIT-6), 36-Item Short Form Health Survey (SF-36) and Visual Analogue Scale
      (VAS), the overall EMPRO score was higher for VAS (73.83) and EQ-5 D (73.81).
      Whereas, FACIT-F and HIT- 6 were just able to meet the minimal threshold of EMPRO
      scoring (50.24 and 59.09, respectively). CONCLUSIONS: Evidence from present
      investigation support that eculizumab significantly improves HRQoL in patients
      with aHUS furthermore, EQ-5 D and VAS instrument should be recommended for
      assessing HRQoL in them. However, selection of PRO instrument for determination
      of QoL in HUS entirely depend upon the study requirements.

PMID- 29363394
TI  - Latest developments in the field of stem cell research and regenerative medicine
      compiled from publicly available information and press releases from nonacademic
      institutions 1 September-30 September 2017.

PMID- 29363395
TI  - Psychological determinants of job retention in multiple sclerosis.
AB  - BACKGROUND: Maintaining paid work is a key issue for people with multiple
      sclerosis (PwMS). Different factors, including psychological attributes, can
      influence job retention. Understanding their role should inform potential
      interventions to help PwMS retain employment. OBJECTIVES: The aim of this study
      was to identify the key factors which improve job retention in an employed cohort
      of PwMS. METHODS: This three-year longitudinal study used validated self
      completed measures of physical and psychological factors at four time points over
      28 months. RESULTS: Of 208 employed PwMS, just over 1 in 10 was no longer working
      at the end of the study. Three variables were predictive of continuing
      employment; low 'work instability' at baseline increased the odds of job
      retention by a factor of 12.76; high levels of self-efficacy by a factor of 4.66
      and being less than 50 years of age increased the odds of job retention by a
      factor of 3.90. Path analysis demonstrated the mediating role of self-efficacy
      between the physical impact of MS and the level of work instability at exit.
      CONCLUSION: Screening for work instability and self-efficacy in a clinical
      setting followed by appropriate interventions to increase self-efficacy and
      reduce work instability could aid job retention in MS.

PMID- 29363397
TI  - A community-based intervention to build community harmony in an Indigenous
      Guatemalan Mining Town.
AB  - The presence of large-scale mining operations poses many threats to communities.
      In a rural community in Guatemala, community leaders were motivated to address
      divisiveness and local conflict that have been exacerbated since the arrival of a
      mining company in the region. Prior research by our team identified spiritual and
      cultural strengths as important sources of strength and resilience in the
      community. We piloted a community-based intervention centred on spiritual and
      cultural practices in the region, to address divisiveness and build community
      harmony. One hundred and seventeen participants from over 18 villages in the
      municipality participated in the workshops and follow-up focus groups. Community
      leaders facilitated the intervention and partnered with the academic researcher
      throughout the research process. Overall, community members and facilitators
      expressed satisfaction with the workshop. Further, our analysis revealed three
      important processes important to the development of community harmony in the
      region: (a) mutual recognition and collectivisation; (b) affirmation of ancestral
      roots and connections to Mother Earth and (c) inspiring action and momentum
      towards solutions. These mechanisms, and the socio-political contexts that
      undermine them, have important implications for how global health programmes are
      developed and how collective processes for well-being are understood within an
      inequitable, conflict-laden world.

PMID- 29363396
TI  - Long-term follow-up of pediatric MS patients starting treatment with injectable
      first-line agents: A multicentre, Italian, retrospective, observational study.
AB  - BACKGROUND: Few data are available on very long-term follow-up of pediatric
      multiple sclerosis (MS) patients treated with disease modifying treatments
      (DMTs). OBJECTIVES: To present a long-term follow-up of a cohort of Pediatric-MS
      patients starting injectable first-line agents. METHODS: Data regarding
      treatments, annualized relapse rate (ARR), Expanded Disability Status Scale
      (EDSS) score, and serious adverse event were collected. Baseline characteristics
      were tested in multivariate analysis to identify predictors of disease evolution.
      RESULTS: In total, 97 patients were followed for 12.5 +/- 3.3 years. They started
      therapy at 13.9 +/- 2.1 years, 88 with interferons and 9 with copaxone. During
      the whole follow-up, 82 patients changed therapy, switching to
      immunosuppressors/second-line treatment in 58% of cases. Compared to pre
      treatment phase, the ARR was significantly reduced during the first treatment
      (from 3.2 +/- 2.6 to 0.7 +/- 1.5, p < 0.001), and it remained low during the
      whole follow-up (0.3 +/- 0.2, p < 0.001). At last observation, 40% had disability
      worsening, but EDSS score remained <4 in 89%. One patient died at age of 23 years
      due to MS. One case of natalizumab-related progressive multifocal encephalopathy
      (PML) was recorded. Starting therapy before 12 years of age resulted in a better
      course of disease in multivariate analysis. CONCLUSION: Pediatric-MS patients
      benefited from interferons/copaxone, but the majority had to switch to more
      powerful drugs. Starting therapy before 12 years of age could lead to a more
      favorable outcome.

PMID- 29363399
TI  - Ocular, otic, nasal, rectal and vaginal formulation innovations and regulatory
      considerations.

PMID- 29363398
TI  - Differential staining of peripheral nuclear chromatin with Acridine orange
      implies an A-form epichromatin conformation of the DNA.
AB  - The chromatin observed by conventional electron microscopy under the nuclear
      envelope constitutes a single layer of dense 30-35 nm granules, while ~30 nm
      fibrils laterally attached to them, form large patches of lamin-associated
      domains (LADs). This particular surface "epichromatin" can be discerned by
      specific (H2A+H2B+DNA) conformational antibody at the inner nuclear envelope and
      around mitotic chromosomes. In order to differentiate the DNA conformation of the
      peripheral chromatin we applied an Acridine orange (AO) DNA structural test
      involving RNAse treatment and the addition of AO after acid pre-treatment. MCF-7
      cells treated in this way revealed yellow/red patches of LADs attached to a thin
      green nuclear rim and with mitotic chromosomes outlined in green, topologically
      corresponding to epichromatin epitope staining by immunofluorescence.
      Differentially from LADs, the epichromatin was unable to provide metachromatic
      staining by AO, unless thermally denatured at 94oC. DNA enrichment in GC
      stretches has been recently reported for immunoprecipitated ~ 1Kb epichromatin
      domains. Together these data suggest that certain epichromatin segments assume
      the relatively hydrophobic DNA A-conformation at the nuclear envelope and surface
      of mitotic chromosomes, preventing AO side dimerisation.  We hypothesize that
      epichromatin domains form nucleosome superbeads. Hydrophobic interactions stack
      these superbeads and align them at the nuclear envelope, while repulsing the
      hydrophilic LADs. The hydrophobicity of epichromatin explains its location at the
      surface of mitotic chromosomes and its function in mediating chromosome
      attachment to the restituting nuclear envelope during telophase.

PMID- 29363400
TI  - Last resting places of the Zambezi Expedition (1858-1864) doctors.

PMID- 29363401
TI  - Editorial.

PMID- 29363408
TI  - Excellent adsorption performance of dibenzothiophene on functionalized low-cost
      activated carbons with different oxidation methods.
AB  - Low-cost activated carbon (KAC) was functionalized by HNO3, (NH4)2S2O8 and air
      oxidation, respectively, to remove dibenzothiophene (DBT) from model fuel. The
      changes in physical and chemical properties of these activated carbons were
      characterized by thermal analysis, elemental analysis, nitrogen adsorption
      apparatus, Raman spectra, scanning electron microscope and Boehm's titration
      method. HNO3 and (NH4)2S2O8 oxidation result in a significant decrease in pore
      structure, while air oxidation only causes slight pore reduction due to the re
      activation by O2. The oxygen-containing functional groups (OFGs) increase
      markedly after oxidative modification, in which (NH4)2S2O8 oxidation is
      considered as the most efficient method with respect to the introduction of OFGs.
      HNO3 and (NH4)2S2O8 oxidation are more selective to generate carboxyls and
      lactones, whereas air oxidation creates more phenols, carbonyls and ethers. The
      DBT adsorption capacity follows the order: NAC (HNO3-oxidized KAC) > OAC (air
      oxidized KAC) > KAC > SAC ((NH4)2S2O8-oxidized KAC), implying the introduction of
      OFGs is beneficial for the DBT adsorption process, especially for selectivity,
      but excessive OFGs have a negative effect on the removal of DBT. Thus, to achieve
      high DBT adsorption performance, there should be a trade-off between the
      micropore volume and the OFGs amount.

PMID- 29363407
TI  - Prophylaxis and treatment of HIV-1 infection in pregnancy - Swedish
      Recommendations 2017.
AB  - Prophylaxis and treatment with antiretroviral drugs have resulted in a very low
      rate of mother-to-child transmission (MTCT) of HIV during recent years.
      Registration of new antiretroviral drugs, modification of clinical praxis,
      updated general treatment guidelines and increasing knowledge about MTCT have
      necessitated regular revisions of the recommendations for 'Prophylaxis and
      treatment of HIV-1 infection in pregnancy'. The Swedish Reference Group for
      Antiviral Therapy (RAV) has updated the recommendations from 2013 at an expert
      meeting 19 September 2017. In the new text, current treatment guidelines for non
      pregnant are considered. The most important revisions are that: (1) Caesarean
      section and infant prophylaxis with three drugs are recommended when maternal HIV
      RNA >150 copies/mL (previously >50 copies/mL). The treatment target of
      undetectable HIV RNA remains unchanged <50 copies/mL; (2) Obstetric management
      and mode of delivery at premature rupture of the membranes and rupture of the
      membranes at full term follow the same procedures as in HIV negative women; (3)
      Vaginal delivery is recommended to a well-treated woman with HIV RNA <150
      copies/mL regardless of gestational age, if no obstetric contraindications are
      present; (4) Treatment during pregnancy should begin as soon as possible and
      should continue after delivery; (5) Ongoing well-functioning HIV treatment at
      pregnancy start should usually be retained; (6) Recommended drugs and drug
      combinations have been updated.

PMID- 29363409
TI  - Decreasing the immunogenicity of arginine deiminase enzyme via structure-based
      computational analysis.
AB  - The clinical applications of therapeutic enzymes are often limited due to their
      immunogenicity. B-cell epitope removal is an effective approach to solve this
      obstacle. The identification of hot spot epitopic residues is a critical step in
      the removal of protein B-cell epitope. Hereof, computational approaches are a
      suitable alternative to costly and labor-intensive experimental approaches.
      Arginine deiminase, a Mycoplasma arginine-catabolizing enzyme, is in the clinical
      trial for treating arginine auxotrophic cancers, especially hepatocellular
      carcinomas and melanomas through depleting plasma arginine and causing cell
      starvation. In this study, arginine deiminase from Mycoplasma hominis (MhADI) was
      computationally analyzed for recognizing and locating its immune-reactive
      regions. The 3D structure of the bioactive form of MhADI was modeled. The B-cell
      epitope mapping of protein was performed using various servers with different
      algorithms. Six segments: 31-40, 48-55, 131-140, 196-206, 294-314, and 331-344
      were predicted to be the consensus immunogenic regions. The modification of
      epitopic hot spot residue was performed to reduce immune-reactiveness. The hot
      spot residue was selected considering a high B-cell epitope score, convexity
      index, surface accessibility, flexibility, and hydrophilicity. The structure
      stability of native and mutant proteins was evaluated through molecular dynamics
      simulation. The E304L mutein was suggested as a lower antigenic and stable enzyme
      derivative.

PMID- 29363410
TI  - Intra-cochlear electrode tip fold-over.
AB  - Cochlear implantation has been performed safely for over two decades but still
      has various minor and major complications. We report two cases of an unusual
      complication of electrode implantation: tip fold-over of the electrode array
      within the cochlea. Both cases required undergoing explantation and re
      implantation. The frequent use of fine and pre-curved electrodes particularly
      with the use of an insertion tool necessitates routine postoperative radiological
      evaluation of the electrode array. Our cases demonstrate the benefit of
      systematic imaging including the possible use of the Cone Beam CT
      intraoperatively.

PMID- 29363411
TI  - Cochlear implant: the family's perspective.
AB  - OBJECTIVE: To understand the family's experience of a child who uses a cochlear
      implant (CI). Specifically, to identify the difficulties, changes, and feelings
      entailed by deafness and the use of the CI; the coping strategies; and to
      understand the role of the family for the child with a CI. METHOD: Qualitative
      research, using Symbolic Interactionism and Straussian Grounded Theory as the
      theoretical and methodological frameworks, respectively. Data collection
      instrument: semi-structured interview. A total of 9 families (32 individuals)
      participated in the study. The children's ages ranged from 6 to 11 years old
      (mean = 8.9 years old). RESULTS: Their experience is described in the following
      categories: Having to fight for results, Coping with difficult situations,
      Recognizing that you are not alone, Learning to overcome, and Having one's life
      restored by the implant. CONCLUSION: Cochlear implantation changes the direction
      of the child and the family's life by restoring the child's opportunity to hear
      and to obtain good results in her personal, social, and academic development.
      Even after implantation, the child continues to experience difficulties and
      requires the family's mobilization in order to be successful. The family is the
      principal actor in the process of the child's rehabilitation.

PMID- 29363412
TI  - Depathologising gender diversity in childhood in the process of ICD revision and
      reform.
AB  - From 2007 on, the World Health Organisation (WHO) has been revising its
      diagnostic manual, the International Statistical Classification of Diseases and
      Related Health Problems (ICD), with approval of ICD-11 due in 2018. The ICD
      revision has prompted debates on diagnostic classifications related to gender
      diversity and gender development processes, and specifically on the 'Gender
      incongruence of childhood' (GIC) code. These debates have taken place at a time
      an emergent trans depathologisation movement is becoming increasingly
      international, and regional and international human rights bodies are recognising
      gender identity as a source of discrimination. With reference to the history of
      diagnostic classification of gender diversity in childhood, this paper conducts a
      literature review of academic, activist and institutional documents related to
      the current discussion on the merits of retaining or abandoning the GIC code.
      Within this broader discussion, the paper reviews in more detail recent
      publications arguing for the abandonment of this diagnostic code drawing upon
      clinical, bioethical and human rights perspectives. The review indicates that
      gender diverse children engaged in exploring their gender identity and expression
      do not benefit from diagnosis. Instead they benefit from support from their
      families, their schools and from society more broadly.

PMID- 29363413
TI  - Introducing Volume 13 of Regenerative Medicine.

PMID- 29363415
TI  - No Increased Risk of Posttransplant Lymphoproliferative Disorder Following
      Alemtuzumab Induction in Kidney Transplant.
AB  - OBJECTIVES: Posttransplant lymphoproliferative disorder is a known complication
      of solid-organ transplant. The use of depleting induction agents has demonstrated
      varying associations with incidence of posttransplant lymphoproliferative
      disorder. Alemtuzumab, a depleting induction agent for kidney transplant
      patients, has shown promising results in reducing the risk of acute rejection and
      graft loss in the first year. Its unique mechanism of depleting both T-cell and B
      cell populations may be beneficial in preventing the occurrence of posttransplant
      lymphoproliferative disorder. MATERIALS AND METHODS: We examined the known risk
      factors for posttransplant lymphoproliferative disorder in the setting of
      alemtuzumab induction to determine whether incidence increases with this
      induction agent. We reviewed medical records of all alemtuzumab-induced kidney
      transplants from March 2006 to November 2015. RESULTS: Of the 675 transplant
      patients who received alemtuzumab induction, 10 developed posttransplant
      lymphoproliferative disorder, with a cumulative incidence rate of 1.5%. All
      diagnosed patients had several known risk factors associated with posttransplant
      lymphoproliferative disorder: 7 with advanced age over 60 years, 5 being
      cytomegalovirus-negative recipients, and all 10 donor kidneys being male patients
      and Epstein-Barr virus positive before transplant. CONCLUSIONS: The incidence
      rate seen in our patient population was within the range of the average in the
      United States but far lower than the incidence rates associated with other
      induction agents. Alemtuzumab is associated with a lower cumulative incidence
      rate of posttransplant lymphoproliferative disorder compared with published
      reports of other induction treatments.

PMID- 29363414
TI  - Molecular interactions of type I and type II positive allosteric modulators with
      the human alpha7 nicotinic acetylcholine receptor: an in silico study.
AB  - The binding site locations and structural components for type I and type II
      positive allosteric modulators (PAMs) of the alpha7 nicotinic acetylcholine
      receptor (nAChR) have not been fully characterized yet. In this regard, homology
      models of the human alpha7 nAChR and halpha7/m5-HT3A chimera, built using the
      crystal structure of the serotonin type 3A receptor (5-EtaTau3AlphaR), were used
      for molecular docking and molecular dynamics simulations to study the molecular
      interactions of selected type I (5-hydroxyindol, NS-1738, and LY-2087101) and
      type II (PNU-120596, PAM-2, and TBS-516) PAMs. The docking results indicate: (1)
      a site located in the extracellular domain (ECD) for type I PAMs such as NS-1738
      and LY-2087101, but not for 5-HI; (2) an overlapping site in the ECD
      transmembrane domain (TMD) junction for all studied PAMs. Additional docking
      results on the halpha7/m5-HT3A chimera supported experimental results indicating
      that the ECD site might be relevant for type I PAM activity; and (3) two TMD
      sites, an intrasubunit site that recognizes type II PAMs, and an intersubunit
      pocket with high specificity for 5-HI (type I PAM). The in silico alpha7TSLMF
      mutant results support the view that M1-Ser223 and M3-Ile281 are key residues for
      the interaction of PAM-2 and PNU-120596 with the intrasubunit cavity. Our in
      silico results are in agreement with experimental data showing that the
      intrasubunit cavity is relevant for the activity of type II PAMs, and suggest
      that the ECD-TMD junction and intersubunit sites could be significant for the
      activity of type I PAMs.

PMID- 29363416
TI  - Impact of Functional Hepatic Venous Outflow Obstruction on Perioperative Outcome
      After Living-Donor Liver Transplant.
AB  - OBJECTIVES: An optimal initial graft function after living-donor liver transplant
      depends on optimal graft hemodynamics. Nonmechanical impediments to free hepatic
      venous outflow, due to elevated central venous pressure, may obstruct the
      "functional" hepatic venous outflow. Here, we evaluated whether central venous
      pressure affected early graft function and outcomes in adult living-donor liver
      transplant recipients. MATERIALS AND METHODS: This prospective observational
      study included 61 living-donor liver transplant recipients without technical
      complications who received transplants from August 2013 to November 2014.
      Hemodynamic variables were measured preoperatively, at anhepatic phase, 30
      minutes postreperfusion, at end of surgery, and during postoperative days 1-5.
      RESULTS: Patients with high central venous pressure showed functional hepatic
      venous outflow obstruction, which caused delayed recovery of graft function.
      Although postoperative central venous pressure was the only identified
      independent risk factor for mortality, all 5 deaths in our study group occurred
      in those who had high central venous pressure at the anhepatic, postreperfusion,
      end of surgery, and postoperative phases. A postoperative central venous pressure
      value of ~11 mm Hg was determined to be the cutoff for high-risk mortality, with
      area under the curve of 0.859 (sensitivity of 80%, specificity of 68%). Increased
      central venous pressure was associated with increased portal venous pressure
      (increase of 45%, range, 28%-89%; P = .001). Central venous pressure at end of
      surgery (r = 0.45, P <= .001) and at posttransplant time points (r = 0.29, P =
      .02) correlated well with portal venous pressure at end of surgery. Other risk
      factors for early allograft dysfunction were Model for End-Stage Liver Disease
      and cardiac output posttransplant. CONCLUSIONS: High central venous pressure,
      modulating portal venous pressure, can result in functional hepatic venous
      outflow obstruction, causing delayed graft function recovery and increased risk
      of mortality. Maintaining a central venous pressure below 11 mm Hg is beneficial.

PMID- 29363417
TI  - Preface.

PMID- 29363418
TI  - Editorial: Neonatal Hyperbilirubinemia.

PMID- 29363419
TI  - Phased secondary small interfering RNAs in Panaxnotoginseng.
AB  - BACKGROUND: Recent results demonstrated that either non-coding or coding genes
      generate phased secondary small interfering RNAs (phasiRNAs) guided by specific
      miRNAs. Till now, there is no studies for phasiRNAs in Panax notoginseng (Burk.)
      F.H. Chen (P. notoginseng), an important traditional Chinese herbal medicinal
      plant species. METHODS: Here we performed a genome-wide discovery of phasiRNAs
      and its host PHAS loci in P. notoginseng by analyzing small RNA sequencing
      profiles. Degradome sequencing profile was used to identify the trigger miRNAs of
      these phasiRNAs and potential targets of phasiRNAs. We also used RLM 5'-RACE to
      validate some of the identified phasiRNA targets. RESULTS: After analyzing 24
      small RNA sequencing profiles of P. notoginseng, 204 and 90 PHAS loci that
      encoded 21 and 24 nucleotide (nt) phasiRNAs, respectively, were identified.
      Furthermore, we found that phasiRNAs produced from some pentatricopeptide repeat
      contain (PPR) genes target another layer of PPR genes as validated by both the
      degradome sequencing profile and RLM 5'-RACE analysis. We also found that miR171
      with 21 nt triggers the generations of 21 nt phasiRNAs from its conserved
      targets. CONCLUSIONS: We validated that some phasiRNAs generated from PPRs and
      TASL genes are functional by targeting other PPRs in trans. These results provide
      the first set of PHAS loci and phasiRNAs in P. notoginseng, and enhance our
      understanding of PHAS in plants.

PMID- 29363420
TI  - Biclustering of transcriptome sequencing data reveals human tissue-specific
      circular RNAs.
AB  - BACKGROUND: Emerging evidence has been experimentally confirmed the tissue
      specific expression of circRNAs (circRNAs). Global identification of human tissue
      specific circRNAs is crucial for the functionality study, which facilitates the
      discovery of circRNAs for potential diagnostic biomarkers. RESULTS: In this
      study, circRNA back-splicing junctions were identified from 465 publicly
      available transcriptome sequencing samples. The number of reads aligned to these
      identified junctions was normalized with the read length and sequence depth for
      each sample. We generated 66 models representing enriched circRNAs among human
      tissue transcriptome through biclustering algorithm. The result provides
      thousands of newly identified human tissue-specific circRNAs. CONCLUSIONS: This
      result suggests that expression of circRNAs is not prompted by random splicing
      error but serving molecular functional roles. We also identified circRNAs
      enriched within circulating system, which, along with identified tissue-specific
      circRNAs, can serve as potential diagnostic biomarkers.

PMID- 29363421
TI  - Mapping HLA-A2, -A3 and -B7 supertype-restricted T-cell epitopes in the
      ebolavirus proteome.
AB  - BACKGROUND: Ebolavirus (EBOV) is responsible for one of the most fatal diseases
      encountered by mankind. Cellular T-cell responses have been implicated to be
      important in providing protection against the virus. Antigenic variation can
      result in viral escape from immune recognition. Mapping targets of immune
      responses among the sequence of viral proteins is, thus, an important first step
      towards understanding the immune responses to viral variants and can aid in the
      identification of vaccine targets. Herein, we performed a large-scale, proteome
      wide mapping and diversity analyses of putative HLA supertype-restricted T-cell
      epitopes of Zaire ebolavirus (ZEBOV), the most pathogenic species among the EBOV
      family. METHODS: All publicly available ZEBOV sequences (14,098) for each of the
      nine viral proteins were retrieved, removed of irrelevant and duplicate
      sequences, and aligned. The overall proteome diversity of the non-redundant
      sequences was studied by use of Shannon's entropy. The sequences were predicted,
      by use of the NetCTLpan server, for HLA-A2, -A3, and -B7 supertype-restricted
      epitopes, which are relevant to African and other ethnicities and provide for
      large (~86%) population coverage. The predicted epitopes were mapped to the
      alignment of each protein for analyses of antigenic sequence diversity and
      relevance to structure and function. The putative epitopes were validated by
      comparison with experimentally confirmed epitopes. RESULTS & DISCUSSION: ZEBOV
      proteome was generally conserved, with an average entropy of 0.16. The 185 HLA
      supertype-restricted T-cell epitopes predicted (82 (A2), 37 (A3) and 66 (B7))
      mapped to 125 alignment positions and covered ~24% of the proteome length. Many
      of the epitopes showed a propensity to co-localize at select positions of the
      alignment. Thirty (30) of the mapped positions were completely conserved and may
      be attractive for vaccine design. The remaining (95) positions had one or more
      epitopes, with or without non-epitope variants. A significant number (24) of the
      putative epitopes matched reported experimentally validated HLA ligands/T-cell
      epitopes of A2, A3 and/or B7 supertype representative allele restrictions. The
      epitopes generally corresponded to functional motifs/domains and there was no
      correlation to localization on the protein 3D structure. These data and the
      epitope map provide important insights into the interaction between EBOV and the
      host immune system.

PMID- 29363422
TI  - Construction of Para rubber tree genome and multi-transcriptome database
      accelerates rubber researches.
AB  - BACKGROUND: Natural rubber is an economically important material. Currently the
      Para rubber tree, Hevea brasiliensis is the main commercial source. Little is
      known about rubber biosynthesis at the molecular level. Next-generation
      sequencing (NGS) technologies brought draft genomes of three rubber cultivars and
      a variety of RNA sequencing (RNA-seq) data. However, no current genome or
      transcriptome databases (DB) are organized by gene. RESULTS: A gene-oriented
      database is a valuable support for rubber research. Based on our original draft
      genome sequence of H. brasiliensis RRIM600, we constructed a rubber tree genome
      and transcriptome DB. Our DB provides genome information including gene
      functional annotations and multi-transcriptome data of RNA-seq, full-length cDNAs
      including PacBio Isoform sequencing (Iso-Seq), ESTs and genome wide transcription
      start sites (TSSs) derived from CAGE technology. Using our original and
      publically available RNA-seq data, we calculated co-expressed genes for
      identifying functionally related gene sets and/or genes regulated by the same
      transcription factor (TF). Users can access multi-transcriptome data through both
      a gene-oriented web page and a genome browser. For the gene searching system, we
      provide keyword search, sequence homology search and gene expression search;
      users can also select their expression threshold easily. CONCLUSION: The rubber
      genome and transcriptome DB provides rubber tree genome sequence and multi
      transcriptomics data. This DB is useful for comprehensive understanding of the
      rubber transcriptome. This will assist both industrial and academic researchers
      for rubber and economically important close relatives such as R. communis, M.
      esculenta and J. curcas. The Rubber Transcriptome DB release 2017.03 is
      accessible at http://matsui-lab.riken.jp/rubber/ .

PMID- 29363423
TI  - InfAcrOnt: calculating cross-ontology term similarities using information flow by
      a random walk.
AB  - BACKGROUND: Since the establishment of the first biomedical ontology Gene
      Ontology (GO), the number of biomedical ontology has increased dramatically.
      Nowadays over 300 ontologies have been built including extensively used Disease
      Ontology (DO) and Human Phenotype Ontology (HPO). Because of the advantage of
      identifying novel relationships between terms, calculating similarity between
      ontology terms is one of the major tasks in this research area. Though
      similarities between terms within each ontology have been studied with in silico
      methods, term similarities across different ontologies were not investigated as
      deeply. The latest method took advantage of gene functional interaction network
      (GFIN) to explore such inter-ontology similarities of terms. However, it only
      used gene interactions and failed to make full use of the connectivity among gene
      nodes of the network. In addition, all existent methods are particularly designed
      for GO and their performances on the extended ontology community remain unknown.
      RESULTS: We proposed a method InfAcrOnt to infer similarities between terms
      across ontologies utilizing the entire GFIN. InfAcrOnt builds a term-gene-gene
      network which comprised ontology annotations and GFIN, and acquires similarities
      between terms across ontologies through modeling the information flow within the
      network by random walk. In our benchmark experiments on sub-ontologies of GO,
      InfAcrOnt achieves a high average area under the receiver operating
      characteristic curve (AUC) (0.9322 and 0.9309) and low standard deviations
      (1.8746e-6 and 3.0977e-6) in both human and yeast benchmark datasets exhibiting
      superior performance. Meanwhile, comparisons of InfAcrOnt results and prior
      knowledge on pair-wise DO-HPO terms and pair-wise DO-GO terms show high
      correlations. CONCLUSIONS: The experiment results show that InfAcrOnt
      significantly improves the performance of inferring similarities between terms
      across ontologies in benchmark set.

PMID- 29363424
TI  - Success: evolutionary and structural properties of amino acids prove effective
      for succinylation site prediction.
AB  - BACKGROUND: Post-translational modification is considered an important biological
      mechanism with critical impact on the diversification of the proteome. Although a
      long list of such modifications has been studied, succinylation of lysine
      residues has recently attracted the interest of the scientific community. The
      experimental detection of succinylation sites is an expensive process, which
      consumes a lot of time and resources. Therefore, computational predictors of this
      covalent modification have emerged as a last resort to tackling lysine
      succinylation. RESULTS: In this paper, we propose a novel computational predictor
      called 'Success', which efficiently uses the structural and evolutionary
      information of amino acids for predicting succinylation sites. To do this, each
      lysine was described as a vector that combined the above information of
      surrounding amino acids. We then designed a support vector machine with a radial
      basis function kernel for discriminating between succinylated and non
      succinylated residues. We finally compared the Success predictor with three state
      of-the-art predictors in the literature. As a result, our proposed predictor
      showed a significant improvement over the compared predictors in statistical
      metrics, such as sensitivity (0.866), accuracy (0.838) and Matthews correlation
      coefficient (0.677) on a benchmark dataset. CONCLUSIONS: The proposed predictor
      effectively uses the structural and evolutionary information of the amino acids
      surrounding a lysine. The bigram feature extraction approach, while retaining the
      same number of features, facilitates a better description of lysines. A support
      vector machine with a radial basis function kernel was used to discriminate
      between modified and unmodified lysines. The aforementioned aspects make the
      Success predictor outperform three state-of-the-art predictors in succinylation
      detection.

PMID- 29363425
TI  - ezTree: an automated pipeline for identifying phylogenetic marker genes and
      inferring evolutionary relationships among uncultivated prokaryotic draft
      genomes.
AB  - BACKGROUND: Inferring phylogenetic trees for newly recovered genomes from
      metagenomic samples is very useful in determining the identities of uncultivated
      microorganisms. Even though 16S ribosomal RNA small subunit genes have been
      established as "gold standard" markers for inferring phylogenetic trees, they
      usually cannot be assembled very well in metagenomes due to shared regions among
      16S genes. Using single-copy marker genes to build genome trees has become
      increasingly popular for uncultivated species. Predefined marker gene sets were
      discovered and have been applied in various genomic studies; however these gene
      sets might not be adequate for novel, uncultivated, draft, or incomplete genomes.
      The automatic identification of marker gene sets among a set of genomes with
      different assembly qualities has thus become a very important task for inferring
      reliable phylogenetic relationships for microbial populations. RESULTS: A
      computational pipeline, ezTree, was developed to automatically identify single
      copy marker genes for a group of genomes and build phylogenetic trees from the
      marker genes. Testing ezTree on a group of proteobacteria species revealed that
      ezTree was highly effective in pinpointing marker genes and constructing reliable
      trees for different groups of bacterial genomes. Applying ezTree to genomes that
      were recently recovered from metagenomes also showed that ezTree can help
      elucidate taxonomic relationships among newly recovered genomes and existing
      ones. CONCLUSIONS: The development of ezTree can help scientists build reliable
      phylogenetic trees for uncultivated species retrieved from environmental samples.
      The uncovered single-copy marker genes may also provide crucial hints for
      understanding shared features of a group of microbes. The ezTree pipeline is
      freely available at https://github.com/yuwwu/ezTree under a GNU GPLv3 license.

PMID- 29363426
TI  - A novel algorithm for finding optimal driver nodes to target control complex
      networks and its applications for drug targets identification.
AB  - BACKGROUND: The advances in target control of complex networks not only can offer
      new insights into the general control dynamics of complex systems, but also be
      useful for the practical application in systems biology, such as discovering new
      therapeutic targets for disease intervention. In many cases, e.g. drug target
      identification in biological networks, we usually require a target control on a
      subset of nodes (i.e., disease-associated genes) with minimum cost, and we
      further expect that more driver nodes consistent with a certain well-selected
      network nodes (i.e., prior-known drug-target genes). RESULTS: Therefore,
      motivated by this fact, we pose and address a new and practical problem called as
      target control problem with objectives-guided optimization (TCO): how could we
      control the interested variables (or targets) of a system with the optional
      driver nodes by minimizing the total quantity of drivers and meantime maximizing
      the quantity of constrained nodes among those drivers. Here, we design an
      efficient algorithm (TCOA) to find the optional driver nodes for controlling
      targets in complex networks. We apply our TCOA to several real-world networks,
      and the results support that our TCOA can identify more precise driver nodes than
      the existing control-fucus approaches. Furthermore, we have applied TCOA to two
      bimolecular expert-curate networks. Source code for our TCOA is freely available
      from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or
      https://github.com/WilfongGuo/guoweifeng . CONCLUSIONS: In the previous
      theoretical research for the full control, there exists an observation and
      conclusion that the driver nodes tend to be low-degree nodes. However, for target
      control the biological networks, we find interestingly that the driver nodes tend
      to be high-degree nodes, which is more consistent with the biological
      experimental observations. Furthermore, our results supply the novel insights
      into how we can efficiently target control a complex system, and especially many
      evidences on the practical strategic utility of TCOA to incorporate prior drug
      information into potential drug-target forecasts. Thus applicably, our method
      paves a novel and efficient way to identify the drug targets for leading the
      phenotype transitions of underlying biological networks.

PMID- 29363427
TI  - GT-WGS: an efficient and economic tool for large-scale WGS analyses based on the
      AWS cloud service.
AB  - BACKGROUND: Whole-genome sequencing (WGS) plays an increasingly important role in
      clinical practice and public health. Due to the big data size, WGS data analysis
      is usually compute-intensive and IO-intensive. Currently it usually takes 30 to
      40 h to finish a 50* WGS analysis task, which is far from the ideal speed
      required by the industry. Furthermore, the high-end infrastructure required by
      WGS computing is costly in terms of time and money. In this paper, we aim to
      improve the time efficiency of WGS analysis and minimize the cost by elastic
      cloud computing. RESULTS: We developed a distributed system, GT-WGS, for large
      scale WGS analyses utilizing the Amazon Web Services (AWS). Our system won the
      first prize on the Wind and Cloud challenge held by Genomics and Cloud Technology
      Alliance conference (GCTA) committee. The system makes full use of the dynamic
      pricing mechanism of AWS. We evaluate the performance of GT-WGS with a 55* WGS
      dataset (400GB fastq) provided by the GCTA 2017 competition. In the best case, it
      only took 18.4 min to finish the analysis and the AWS cost of the whole process
      is only 16.5 US dollars. The accuracy of GT-WGS is 99.9% consistent with that of
      the Genome Analysis Toolkit (GATK) best practice. We also evaluated the
      performance of GT-WGS performance on a real-world dataset provided by the XiangYa
      hospital, which consists of 5* whole-genome dataset with 500 samples, and on
      average GT-WGS managed to finish one 5* WGS analysis task in 2.4 min at a cost of
      $3.6. CONCLUSIONS: WGS is already playing an important role in guiding
      therapeutic intervention. However, its application is limited by the time cost
      and computing cost. GT-WGS excelled as an efficient and affordable WGS analyses
      tool to address this problem. The demo video and supplementary materials of GT
      WGS can be accessed at https://github.com/Genetalks/wgs_analysis_demo .

PMID- 29363428
TI  - A survey on cellular RNA editing activity in response to Candida albicans
      infections.
AB  - BACKGROUND: Adenosine-to-Inosine (A-to-I) RNA editing is catalyzed by the
      adenosine deaminase acting on RNA (ADAR) family of enzymes, which induces
      alterations in mRNA sequence. It has been shown that A-to-I RNA editing events
      are of significance in the cell's innate immunity and cellular response to viral
      infections. However, whether RNA editing plays a role in cellular response to
      microorganism/fungi infection has not been determined. Candida albicans, one of
      the most prevalent human pathogenic fungi, usually act as a commensal on skin and
      superficial mucosal, but has been found to cause candidiasis in immunosuppression
      patients. Previously, we have revealed the up-regulation of A-to-I RNA editing
      activity in response to different types of influenza virus infections. The
      current work is designed to study the effect of microorganism/fungi infection on
      the activity of A-to-I RNA editing in infected hosts. RESULTS: We first detected
      and characterized the A-to-I RNA editing events in oral epithelial cells (OKF6)
      and primary human umbilical vein endothelial cells (HUVEC), under normal growth
      condition or with C. albicans infection. Eighty nine thousand six hundred forty
      eight and 60,872 A-to-I editing sites were detected in normal OKF6 and HUVEC
      cells, respectively. They were validated against the RNA editing databases,
      DARNED, RADAR, and REDIportal with 50, 80, and 80% success rates, respectively.
      While over 95% editing sites were detected in Alu regions, among the rest of the
      editing sites in non repetitive regions, the majority was located in introns and
      UTRs. The distributions of A-to-I editing activity and editing depth were
      analyzed during the course of C. albicans infection. While the normalized editing
      levels of common editing sites exhibited a significant increase, especially in
      Alu regions, no significant change in the expression of ADAR1 or ADAR2 was
      observed. Second, we performed further analysis on data from in vivo mouse study
      with C. albicans infection. One thousand one hundred thirty three and 955 A-to-I
      editing sites were identified in mouse tongue and kidney tissues, respectively.
      The number of A-to-I editing events was much smaller than in human epithelial or
      endothelial cells, due to the lack of Alu elements in mouse genome. Furthermore,
      during the course of C. albicans infection we observed stable level of A-to-I
      editing activity in 131 and 190 common editing sites in the mouse tongue and
      kidney tissues, and found no significant change in ADAR1 or ADAR2 expression
      (with the exception of ADAR2 displaying a significant increase at 12 h after
      infection in mouse kidney tissue before returning to normal). CONCLUSIONS: This
      work represents the first comprehensive analysis of A-to-I RNA editome in human
      epithelial and endothelial cells. C. albicans infection of human epithelial and
      endothelial cells led to the up-regulation of A-to-I editing activities, through
      a mechanism different from that of viral infections in human hosts. However, the
      in vivo mouse model with C. albicans infection did not show significant changes
      in A-to-I editing activities in tongue and kidney tissues. The different results
      in the mouse model were likely due to the presence of more complex in vivo
      environments, e.g. circulation and mixed cell types.

PMID- 29363429
TI  - Characteristics of functional enrichment and gene expression level of human
      putative transcriptional target genes.
AB  - BACKGROUND: Transcriptional target genes show functional enrichment of genes.
      However, how many and how significantly transcriptional target genes include
      functional enrichments are still unclear. To address these issues, I predicted
      human transcriptional target genes using open chromatin regions, ChIP-seq data
      and DNA binding sequences of transcription factors in databases, and examined
      functional enrichment and gene expression level of putative transcriptional
      target genes. RESULTS: Gene Ontology annotations showed four times larger numbers
      of functional enrichments in putative transcriptional target genes than gene
      expression information alone, independent of transcriptional target genes. To
      compare the number of functional enrichments of putative transcriptional target
      genes between cells or search conditions, I normalized the number of functional
      enrichment by calculating its ratios in the total number of transcriptional
      target genes. With this analysis, native putative transcriptional target genes
      showed the largest normalized number of functional enrichments, compared with
      target genes including 5-60% of randomly selected genes. The normalized number of
      functional enrichments was changed according to the criteria of enhancer-promoter
      interactions such as distance from transcriptional start sites and orientation of
      CTCF-binding sites. Forward-reverse orientation of CTCF-binding sites showed
      significantly higher normalized number of functional enrichments than the other
      orientations. Journal papers showed that the top five frequent functional
      enrichments were related to the cellular functions in the three cell types. The
      median expression level of transcriptional target genes changed according to the
      criteria of enhancer-promoter assignments (i.e. interactions) and was correlated
      with the changes of the normalized number of functional enrichments of
      transcriptional target genes. CONCLUSIONS: Human putative transcriptional target
      genes showed significant functional enrichments. Functional enrichments were
      related to the cellular functions. The normalized number of functional
      enrichments of human putative transcriptional target genes changed according to
      the criteria of enhancer-promoter assignments and correlated with the median
      expression level of the target genes. These analyses and characters of human
      putative transcriptional target genes would be useful to examine the criteria of
      enhancer-promoter assignments and to predict the novel mechanisms and factors
      such as DNA binding proteins and DNA sequences of enhancer-promoter interactions.

PMID- 29363431
TI  - PGAP-X: extension on pan-genome analysis pipeline.
AB  - BACKGROUND: Since PGAP (pan-genome analysis pipeline) was published in 2012, it
      has been widely employed in bacterial genomics research. Though PGAP has
      integrated several modules for pan-genomics analysis, how to properly and
      effectively interpret and visualize the results data is still a challenge.
      RESULT: To well present bacterial genomic characteristics, a novel cross-platform
      software was developed, named PGAP-X. Four kinds of data analysis modules were
      developed and integrated: whole genome sequences alignment, orthologous genes
      clustering, pan-genome profile analysis, and genetic variants analysis. The
      results from these analyses can be directly visualized in PGAP-X. The modules for
      data visualization in PGAP-X include: comparison of genome structure, gene
      distribution by conservation, pan-genome profile curve and variation on genic and
      genomic region. Meanwhile, result data produced by other programs with similar
      function can be imported to be further analyzed and visualized in PGAP-X. To test
      the performance of PGAP-X, we comprehensively analyzed 14 Streptococcus pneumonia
      strains and 14 Chlamydia trachomatis. The results show that, S. pneumonia strains
      have higher diversity on genome structure and gene contents than C. trachomatis
      strains. In addition, S. pneumonia strains might have suffered many evolutionary
      events, such genomic rearrangements, frequent horizontal gene transfer,
      homologous recombination, and other evolutionary process. CONCLUSION: Briefly,
      PGAP-X directly presents the characteristics of bacterial genomic diversity with
      different visualization methods, which could help us to intuitively understand
      dynamics and evolution in bacterial genomes. The source code and the pre-complied
      executable programs are freely available from http://pgapx.ybzhao.com .

PMID- 29363430
TI  - A comprehensive study on cellular RNA editing activity in response to infections
      with different subtypes of influenza a viruses.
AB  - BACKGROUND: RNA editing is an important mechanism that expands the diversity and
      complexity of genetic codes. The conversions of adenosine (A) to inosine (I) and
      cytosine (C) to uridine (U) are two prominent types of RNA editing in animals.
      The roles of RNA editing events have been implicated in important biological
      pathways. Cellular RNA editing activity in response to influenza A virus
      infection has not been fully characterized in human and avian hosts. This study
      was designed as a big data analysis to investigate the role and response of RNA
      editing in epithelial cells during the course of infection with various subtypes
      of influenza A viruses. RESULTS: Using a bioinformatics pipeline modified from
      our previous study, we characterized the profiles of A-to-I and C-to-U RNA
      editing events in human epithelial cells during the course of influenza A virus
      infection. Our results revealed a striking diversity of A-to-I RNA editing
      activities in human epithelial cells in responses to different subtypes of
      influenza A viruses. The infection of H1N1 and H3N2 significantly up-regulated
      normalized A-to-I RNA editing levels in human epithelial cells, whereas that of
      H5N1 did not change it and H7N9 infection significantly down-regulated normalized
      A-to-I editing level in A549 cells. Next, the expression levels of ADAR and
      APOBEC enzymes responsible for A-to-I and C-to-U RNA editing during the course of
      virus infection were examined. The increase of A-to-I RNA editing activities in
      infections with some influenza A viruses (H1N1 and H3N2) is linked to the up
      regulation of ADAR1 but not ADAR2. Further, the pattern recognition receptors of
      human epithelial cells infected with H1N1, H3N2, H5N1 and H7N9 were examined.
      Variable responsive changes in gene expression were observed with RIG-I like
      receptors and Toll like receptors. Finally, the effect of influenza A virus
      infection on cellular RNA editing activity was also analyzed in avian hosts.
      CONCLUSION: This work represents the first comprehensive study of cellular RNA
      editing activity in response to different influenza A virus infections in human
      and avian hosts, highlighting the critical role of RNA editing in innate immune
      response and the pathogenicity of different subtypes of influenza A viruses.

PMID- 29363432
TI  - A bioinformatics potpourri.
AB  - The 16th International Conference on Bioinformatics (InCoB) was held at Tsinghua
      University, Shenzhen from September 20 to 22, 2017. The annual conference of the
      Asia-Pacific Bioinformatics Network featured six keynotes, two invited talks, a
      panel discussion on big data driven bioinformatics and precision medicine, and 66
      oral presentations of accepted research articles or posters. Fifty-seven articles
      comprising a topic assortment of algorithms, biomolecular networks, cancer and
      disease informatics, drug-target interactions and drug efficacy, gene regulation
      and expression, imaging, immunoinformatics, metagenomics, next generation
      sequencing for genomics and transcriptomics, ontologies, post-translational
      modification, and structural bioinformatics are the subject of this editorial for
      the InCoB2017 supplement issues in BMC Genomics, BMC Bioinformatics, BMC Systems
      Biology and BMC Medical Genomics. New Delhi will be the location of InCoB2018,
      scheduled for September 26-28, 2018.

PMID- 29363434
TI  - Gorham-Stout disease of the temporal bone involving the temporomandibular joint.
AB  - BACKGROUND: Gorham-Stout disease of the skull is a very rare entity. It presents
      with gradual bone resorption, and proliferation of lymphoid and vascular channels
      within the bony matrix. This is often a diagnosis of exclusion confirmed with
      serial imaging and based on radiological evidence. CASE REPORT: A case of Gorham
      Stout disease of the temporal bone involving the temporomandibular joint, and
      presenting with sensorineural hearing loss and recurrent temporomandibular joint
      dislocation, is reported. The findings are presented and the literature on this
      condition is reviewed. CONCLUSION: ENT and maxillofacial surgeons should be aware
      of this extremely rare cause of temporomandibular joint dislocation and ear
      symptoms. Imaging comprising computed tomography and magnetic resonance imaging
      is crucial to achieving a diagnosis, which may only become evident after repeated
      imaging follow up. Symptomatic treatment is advised, with the option of anti
      osteoclastic medication and radiotherapy indicated for advanced cases. Surgery is
      only recommended for complications including involvement of neurovascular
      structures.

PMID- 29363435
TI  - Defect Rates in Touchless Versus Mechanical Hand Hygiene Dispensers.

PMID- 29363436
TI  - Factors Associated with the Use of Fecal Microbiota Transplant in Patients with
      Recurrent Clostridium difficile Infections.
AB  - OBJECTIVE To identify the factors associated with first Clostridium difficile
      infection (CDI) that predict fecal microbiota transplantation (FMT) for recurrent
      CDI DESIGN We carried out a retrospective single-center cohort study to compare
      the clinical characteristics of 200 patients who underwent FMT for recurrent CDI
      to 75 patients who did not. SETTING A single academic hospital in the United
      States PATIENTS Adult patients RESULTS The time from first to second CDI
      correlated to subsequent FMT use. Concomitant inflammatory bowel disease (IBD;
      P=.002), use of immunosuppressive therapy (P=.04), and use of metronidazole
      within 2 months before the first CDI (P=.02) correlated positively to subsequent
      FMT in univariate analysis. The use of oral vancomycin for first CDI was more
      common in those who required FMT than those who did not in univariate (P=.02) and
      multivariate (P=.03) analyses. In contrast, intravenous vancomycin use within 2
      months before the first CDI reduced the risk for FMT in univariate P=.000003) and
      multivariate (P=.0001) analyses. Black patients with recurrent CDI were less
      likely to receive FMT than white patients (P=.00005). Patients who received FMT
      were also less likely to have comorbidities. CONCLUSIONS This study provides
      important insights into the factors predictive for FMT in patients with recurrent
      CDI and highlights the potential racial and medical characteristics that affect
      the access of the patients to FMT. Infect Control Hosp Epidemiol 2018;39:302-306.

PMID- 29363433
TI  - Discovery of cell-type specific DNA motif grammar in cis-regulatory elements
      using random Forest.
AB  - BACKGROUND: It has been observed that many transcription factors (TFs) can bind
      to different genomic loci depending on the cell type in which a TF is expressed
      in, even though the individual TF usually binds to the same core motif in
      different cell types. How a TF can bind to the genome in such a highly cell-type
      specific manner, is a critical research question. One hypothesis is that a TF
      requires co-binding of different TFs in different cell types. If this is the
      case, it may be possible to observe different combinations of TF motifs - a motif
      grammar - located at the TF binding sites in different cell types. In this study,
      we develop a bioinformatics method to systematically identify DNA motifs in TF
      binding sites across multiple cell types based on published ChIP-seq data, and
      address two questions: (1) can we build a machine learning classifier to predict
      cell-type specificity based on motif combinations alone, and (2) can we extract
      meaningful cell-type specific motif grammars from this classifier model. RESULTS:
      We present a Random Forest (RF) based approach to build a multi-class classifier
      to predict the cell-type specificity of a TF binding site given its motif
      content. We applied this RF classifier to two published ChIP-seq datasets of TF
      (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that
      motif combinations alone are indeed predictive of cell types. Furthermore, we
      present a rule mining approach to extract the most discriminatory rules in the RF
      classifier, thus allowing us to discover the underlying cell-type specific motif
      grammar. CONCLUSIONS: Our bioinformatics analysis supports the hypothesis that
      combinatorial TF motif patterns are cell-type specific.

PMID- 29363437
TI  - Presentation of automated procedural guidance in surgical simulation: results of
      two randomised controlled trials.
AB  - OBJECTIVE: To investigate the effectiveness and usability of automated procedural
      guidance during virtual temporal bone surgery. METHODS: Two randomised controlled
      trials were performed to evaluate the effectiveness, for medical students, of two
      presentation modalities of automated real-time procedural guidance in virtual
      reality simulation: full and step-by-step visual presentation of drillable areas.
      Presentation modality effectiveness was determined through a comparison of
      participants' dissection quality, evaluated by a blinded otologist, using a
      validated assessment scale. RESULTS: While the provision of automated guidance on
      procedure improved performance (full presentation, p = 0.03; step-by-step
      presentation, p < 0.001), usage of the two different presentation modalities was
      vastly different (full presentation, 3.73 per cent; step-by-step presentation,
      60.40 per cent). CONCLUSION: Automated procedural guidance in virtual temporal
      bone surgery is effective in improving trainee performance. Step-by-step
      presentation of procedural guidance was engaging, and therefore more likely to be
      used by the participants.

PMID- 29363438
TI  - To Be a CLABSI or Not to Be a CLABSI-That is the Question: The Epidemiology of
      BSI in a Large ECMO Population.

PMID- 29363439
TI  - A morphological and molecular study of adults and metacercariae of Hysteromorpha
      triloba (Rudolpi, 1819), Lutz 1931 (Diplostomidae) from the Neotropical region.
AB  - Adults of Hysteromorpha triloba (Rudolpi, 1819), Lutz, 1931 inhabit primarily the
      intestine of cormorants across the globe, whereas metacercariae have been found
      in the body cavity of freshwater fishes of the families Cyprinidae, Ictaluridae,
      Ariidae, Pimelodidae and Catostomidae. In this study, adults and metacercariae
      identified as H. triloba were collected from the Neotropical cormorant
      (Nannopterum brasilianus) and from the Mexican tetra fish (Astyanax mexicanus)
      from the Gulf of Mexico and Pacific Ocean slopes in the Neotropical region.
      Partial DNA sequences of the mitochondrial gene cytochrome c oxidase subunit I
      (cox 1) and the internal transcribed spacers (ITS1, 5.8S and ITS2) of nuclear
      ribosomal DNA were generated for both developmental stages, and were compared
      with available sequences of H. triloba from the Nearctic region. The genetic
      divergence between metacercariae and adults of H. triloba from the Neotropical
      and Nearctic region (Canada) associated with the double-crested cormorant
      (Nannopterum auritus), ranged from 0 to 5.5% for cox 1 and from 0 to 0.2% for
      ITS. Phylogenetic analyses inferred with both molecular markers using maximum
      likelihood and Bayesian inference placed the adults and metacercariae in a single
      clade, confirming that both stages are conspecific. Our data confirmed that H.
      triloba is a widely distributed species across the Americas, parasitizing both
      the Neotropical and Nearctic cormorants in Argentina, Brazil, Venezuela, Mexico,
      USA and Canada.

PMID- 29363440
TI  - Hospital Water Management Programs for Legionella Prevention, Minnesota, 2017.
AB  - Infection preventionists at Minnesota hospitals were surveyed to determine
      whether they had Legionella water management plans. Of 137 hospitals, 84 (61%)
      responded. Among them, 27% hospitals had a water management plan, 21% regularly
      sampled for Legionella, and 51% had knowledge of ASHRAE Legionella prevention
      standards. Significant changes are needed to protect patients from nosocomial
      infection. Infect Control Hosp Epidemiol 2018;39:336-338.

PMID- 29363442
TI  - Case Report: Family Cluster of Japanese Spotted Fever.
AB  - Spotted fever group rickettsioses are transmitted by several types of arthropods
      (including ticks, chiggers, fleas, and lice) and are distributed worldwide.
      Japanese spotted fever (JSF) was discovered as an emerging rickettsiosis in 1984.
      The annual number of cases has increased 3-fold during the last decade. In Japan,
      JSF has been mainly reported in an area with warm climate that borders the
      Pacific Ocean. We describe a family/neighborhood cluster of three cases of JSF in
      an area of Japan that had previously not been considered endemic.

PMID- 29363441
TI  - Severe Strongyloidiasis in Solid Organ Transplant Recipients: Should We
      Preventively Treat the Recipient, the Donor, or Both?
AB  - Strongyloidiasis is caused by a soil-transmitted helminth that is endemic in
      tropical and subtropical countries. The parasite can complete its life cycle
      without leaving the host, allowing autoinfection and persistence. The risk of
      infection in travelers is low, but the disease may become lethal following
      immunosuppression. In case of solid organ transplantation, the risk of donor
      transmission has been suspected for several years. However, the management of
      live donors in this context has only recently been considered, and no guidelines
      exist for the management of deceased donors. To highlight the complexity of
      diagnosing, treating, and preventing strongyloidiasis donor transmission, we
      describe a case of possible transmission of severe strongyloidiasis to a kidney
      transplant recipient with limited travel history. Taking into account the
      difficulty of diagnosing chronic strongyloidiasis infection and the increase in
      travel and immunosuppressive treatments, we recommend pragmatic management
      guidelines to limit the risks of infection.

PMID- 29363443
TI  - A Cross-Sectional Study on Intestinal Parasitic Infections in Children in
      Suburban Public Primary Schools, Saraburi, the Central Region of Thailand.
AB  - Intestinal parasitic infection rate among school-aged children in Thailand has
      been decreasing. However, certain intestinal parasites remain problematic in some
      regions. This cross-sectional study was conducted between February and September
      2016 in three suburban government primary schools (KK, BR, and HK), Saraburi,
      Thailand. Stool was collected from 263 asymptomatic subjects (4-15 years old),
      using simple direct smear, formalin-ether concentration, Boeck and Drbohlav's
      Locke-Egg-Serum (LES) medium culture, and agar plate culture. A self-administered
      questionnaire was used to collect data about lifestyle and socioeconomic status.
      The overall rate of intestinal parasites was 22.1% (15.6% single infection and
      6.5% multiple infections). The helminths involving the digestive system found
      were Strongyloides stercoralis (1.5%) and Opisthorchis viverrini (0.4%). For
      protozoan infection, the major cause was Blastocystis hominis (17.5%). The other
      protozoa included Endolimax nana (4.6%), Entamoeba coli (3.4%), Entamoeba
      histolytica/Entamoeba dispar (1.1%), and Giardia intestinalis (0.8%). The
      sensitivity for the detection of B. hominis increased with the LES culture
      technique. The infection rate of each organism was not significantly different
      among the three schools except for B. hominis which showed the highest prevalence
      in the HK school (P = 0.001). This was correlated with the questionnaire results
      in which the HK school showed the highest risk of drinking contaminated water (P
      = 0.004). The present study emphasized the persistent problems of protozoan
      infections among suburban school-aged children. Lifestyle was still an important
      factor for intestinal parasitic infections among suburban school-aged Thai
      children in this study. Health education as well as routine surveillance was
      necessary to control the infections.

PMID- 29363445
TI  - Diarrhegenic Escherichia coli Replaces Shigella spp. as the Predominant Bacteria
      Causing Childhood Diarrhea in Andaman and Nicobar Islands, India.

PMID- 29363444
TI  - Escherichia coli Contamination across Multiple Environmental Compartments (Soil,
      Hands, Drinking Water, and Handwashing Water) in Urban Harare: Correlations and
      Risk Factors.
AB  - Escherichia coli pathotypes (i.e., enteropathogenic and enterotoxigenic) have
      been identified among the pathogens most responsible for moderate-to-severe
      diarrhea in low- and middle-income countries (LMICs). Pathogenic E. coli are
      transmitted from infected human or animal feces to new susceptible hosts via
      environmental reservoirs such as hands, water, and soil. Commensal E. coli, which
      includes nonpathogenic E. coli strains, are widely used as fecal bacteria
      indicator, with their presence associated with increased likelihood of enteric
      pathogens and/or diarrheal disease. In this study, we investigated E. coli
      contamination in environmental reservoirs within households (N = 142) in high
      population density communities of Harare, Zimbabwe. We further assessed the
      interconnectedness of the environmental compartments by investigating
      associations between, and household-level risk factors for, E. coli
      contamination. From the data we collected, the source and risk factors for E.
      coli contamination are not readily apparent. One notable exception is the
      presence of running tap water on the household plot, which is associated with
      significantly less E. coli contamination of drinking water, handwashing water,
      and hands after handwashing. In addition, E. coli levels on hands after washing
      are significantly associated with handwashing water contamination, hand
      contamination before washing, and diarrhea incidence. Finally, we observed that
      animal ownership increases E. coli contamination in soil, and E. coli in soil are
      correlated with contamination on hands before washing. This study highlights the
      complexity of E. coli contamination in household environments within LMICs. More,
      larger, studies are needed to better identify sources and exposure pathways of E.
      coli-and enteric pathogens generally-to identify effective interventions.

PMID- 29363446
TI  - Safety and Immunogenicity of a Tetravalent Dengue DNA Vaccine Administered with a
      Cationic Lipid-Based Adjuvant in a Phase 1 Clinical Trial.
AB  - We conducted an open label, dose escalation Phase 1 clinical trial of a
      tetravalent dengue DNA vaccine (TVDV) formulated in Vaxfectin(r) to assess safety
      and immunogenicity. A total of 40 dengue- and flavivirus-naive volunteers
      received either low-dose (1 mg) TVDV alone (N = 10, group 1), low-dose TVDV (1
      mg) formulated in Vaxfectin (N = 10, group 2), or high-dose TVDV (2 mg, group 3)
      formulated in Vaxfectin(r) (N = 20). Subjects were immunized intramuscularly with
      three doses on a 0-, 30-, 90-day schedule and monitored. Blood samples were
      obtained after each immunization and various time points thereafter to assess
      anti-dengue antibody and interferon gamma (IFNgamma) T-cell immune responses. The
      most common adverse events (AEs) across all groups included mild to moderate pain
      and tenderness at the injection site, which typically resolved within 7 days.
      Common solicited signs and symptoms included fatigue (42.5%), headache (45%), and
      myalgias (47.5%). There were no serious AEs related to the vaccine or study
      procedures. No anti-dengue antibody responses were detected in group 1 subjects
      who received all three immunizations. There were minimal enzyme-linked
      immunosorbent assay and neutralizing antibody responses among groups 2 and 3
      subjects who completed the immunization schedule. By contrast, IFNgamma T-cell
      responses, regardless of serotype specificity, occurred in 70%, 50%, and 79% of
      subjects in groups 1, 2, and 3, respectively. The largest IFNgamma T-cell
      responses were among group 3 subjects. We conclude that TVDV was safe and well
      tolerated and elicited predominately anti-dengue T-cell IFNgamma responses in a
      dose-related fashion.

PMID- 29363448
TI  - Measuring User Compliance and Cost Effectiveness of Safe Drinking Water Programs:
      A Cluster-Randomized Study of Household Ultraviolet Disinfection in Rural Mexico.
AB  - Low adoption and compliance levels for household water treatment and safe storage
      (HWTS) technologies have made it challenging for these systems to achieve
      measurable health benefits in the developing world. User compliance remains an
      inconsistently defined and poorly understood feature of HWTS programs. In this
      article, we develop a comprehensive approach to understanding HWTS compliance.
      First, our Safe Drinking Water Compliance Framework disaggregates and measures
      the components of compliance from initial adoption of the HWTS to exclusive
      consumption of treated water. We apply this framework to an ultraviolet (UV)
      based safe water system in a cluster-randomized controlled trial in rural Mexico.
      Second, we evaluate a no-frills (or "Basic") variant of the program as well as an
      improved (or "Enhanced") variant, to test if subtle changes in the user interface
      of HWTS programs could improve compliance. Finally, we perform a full-cost
      analysis of both variants to assess their cost effectiveness (CE) in achieving
      compliance. We define "compliance" strictly as the habit of consuming safe water.
      We find that compliance was significantly higher in the groups where the UV
      program variants were rolled out than in the control groups. The Enhanced variant
      performed better immediately postintervention than the Basic, but compliance (and
      thus CE) degraded with time such that no effective difference remained between
      the two versions of the program.

PMID- 29363447
TI  - Emerging Pyrethroid Resistance among Anopheles arabiensis in Kenya.
AB  - Vector control programs, particularly in the form of insecticide-treated bed nets
      (ITNs), are essential for achieving malaria elimination goals. Recent reports of
      increasing knockdown resistance (kdr) mutation frequencies for Anopheles
      arabiensis in Western Kenya heightens the concern on the future effectiveness of
      ITNs in Kenya. We examined resistance in An. arabiensis populations across Kenya
      through kdr mutations and World Health Organization-recommended bioassays. We
      detected two kdr alleles, L1014F and L1014S. Kdr mutations were found in five of
      the 11 study sites, with mutation frequencies ranging from 3% to 63%. In two
      Western Kenya populations, the kdr L1014F allele frequency was as high as 10%.
      The L1014S frequency was highest at Chulaimbo at 55%. Notably, the kdr L1014F
      mutation was found to be associated with pyrethroid resistance at Port Victoria,
      but kdr mutations were not significantly associated with resistance at Chulaimbo,
      which had the highest kdr mutation frequency among all sites. This study
      demonstrated the emerging pyrethroid resistance in An. arabiensis and that
      pyrethroid resistance may be related to kdr mutations. Resistance monitoring and
      management are urgently needed for this species in Kenya where resistance is
      emerging and its abundance is becoming predominant. Kdr mutations may serve as a
      biomarker for pyrethroid resistance in An. arabiensis.

PMID- 29363449
TI  - Genetic Diversity of the Plasmodium falciparum Glutamate-Rich Protein R2 Region
      Before and Twelve Years after Introduction of Artemisinin Combination Therapies
      among Febrile Children in Nigeria.
AB  - The genetic diversity of glutamate-rich protein (GLURP) R2 region in Plasmodium
      falciparum isolates collected before and 12 years after the introduction of
      artemisinin combination treatment of malaria in Osogbo, Osun State, Nigeria, was
      compared in this study. Blood samples were collected on filter paper in 2004 and
      2015 from febrile children from ages 1-12 years. The R2 region of the GLURP gene
      was genotyped using nested polymerase chain reaction and by nucleotide
      sequencing. In all, 12 GLURP alleles were observed in a total of 199 samples
      collected in the two study years. The multiplicity of infection (MOI) marginally
      increased over the two study years; however, the differences were statistically
      insignificant (2004 samples MOI = 1.23 versus 2015 samples MOI = 1.47). Some
      alleles were stable in their prevalence, whereas two GLURP alleles, VIII and XI,
      showed considerable variability between both years. This variability was
      replicated when GLURP sequences from other regions were compared with ours. The
      expected heterozygosity (He) values (He = 0.87) were identical for the two
      groups. High variability in the rearrangement of the amino acid repeat units in
      the R2 region were observed, with the amino acid repeat sequence
      DKNEKGQHEIVEVEEILPE more prevalent in both years, compared with the two other
      repeat sequences observed in the study. The parasite population characterized in
      this study displayed extensive genetic diversity. The detailed genetic profile of
      the GLURP R2 region has the potential to help guide further epidemiological
      studies aimed toward the rational design of novel chemotherapies that are
      antagonistic toward malaria.

PMID- 29363450
TI  - Case Report: Chorioamnionitis and Premature Delivery due to Burkholderia
      pseudomallei Infection in Pregnancy.
AB  - We report a case of placental infection leading to preterm delivery in a mother
      diagnosed with septicemia and pneumonia due to Burkholderia pseudomallei in
      pregnancy. Placental infection occurred despite prolonged ceftazidime therapy.

PMID- 29363451
TI  - Case Report: An Acute Chikungunya Infection and a Recent Secondary Dengue
      Infection in a Peripartum Case in Ecuador.
AB  - Dengue virus (DENV) and chikungunya virus (CHIKV) are transmitted by the same
      mosquito vectors and now co-circulate in many parts of the world; however,
      coinfections and serial infections are not often diagnosed or reported. A 38-week
      pregnant woman was admitted to the hospital with a diagnosis of suspected DENV
      and CHIKV in southern coastal Ecuador. The pregnancy was complicated by mild
      polyhydramnios and fetal tachycardia, and a healthy newborn was born. The patient
      was positive for a recent secondary DENV infection (Immunoglobulin M and
      Immunoglobulin G positive) and an acute CHIKV infection (real-time reverse
      transcriptase polymerase chain reaction positive) (Asian genotype). The newborn
      was not tested for either virus. This case resulted in a benign clinical course
      with a favorable pregnancy outcome.

PMID- 29363452
TI  - Reimagining the Research Approach to Tuberculosis?.
AB  - Controlling and ultimately ending tuberculosis (TB) as a public health scourge
      will require a multifaceted and comprehensive approach involving the
      intensification of public health efforts, including scaling-up the delivery of
      current diagnostic, preventive, and therapeutic tools. However, a critically
      important element in the effort to end TB is an accelerated biomedical research
      effort to address the many unanswered questions about the disease process itself
      and to develop improved and innovative countermeasures. An intensive effort
      toward these research goals will facilitate the achievement of the aspirational
      goal of ending TB.

PMID- 29363453
TI  - Impacts of Antimalarial Drugs on Plasmodium falciparum Drug Resistance Markers,
      Western Kenya, 2003-2015.
AB  - Antimalarial drug resistance has threatened global malaria control since
      chloroquine (CQ)-resistant Plasmodium falciparum emerged in Asia in the 1950s.
      Understanding the impacts of changing antimalarial drug policy on resistance is
      critical for resistance management. Plasmodium falciparum isolates were collected
      from 2003 to 2015 in western Kenya and analyzed for genetic markers associated
      with resistance to CQ (Pfcrt), sulfadoxine-pyrimethamine (SP) (Pfdhfr/Pfdhps),
      and artemether-lumefantrine (AL) (PfKelch13/Pfmdr1) antimalarials. In addition,
      household antimalarial drug use surveys were administered. Pfcrt 76T prevalence
      decreased from 76% to 6% from 2003 to 2015. Pfdhfr/Pfdhps quintuple mutants
      decreased from 70% in 2003 to 14% in 2008, but increased to near fixation by
      2015. SP "super resistant" alleles Pfdhps 581G and 613S/T were not detected in
      the 2015 samples that were assessed. The Pfmdr1 N86-184F-D1246 haplotype
      associated with decreased lumefantrine susceptibility increased significantly
      from 4% in 2005 to 51% in 2015. No PfKelch13 mutations that have been previously
      associated with artemisinin resistance were detected in the study populations.
      The increase in Pfdhfr/Pfdhps quintuple mutants that associates with SP
      resistance may have resulted from the increased usage of SP for intermittent
      preventative therapy in pregnancy (IPTp) and for malaria treatment in the
      community. Prevalent Pfdhfr/Pfdhps mutations call for careful monitoring of SP
      resistance and effectiveness of the current IPTp program in Kenya. In addition,
      the commonly occurring Pfmdr1 N86-184F-D1246 haplotype associated with increased
      lumefantrine tolerance calls for surveillance of AL efficacy in Kenya, as well as
      consideration for a rotating artemisinin-combination therapy regimen.

PMID- 29363454
TI  - Effect of Health Care on Quality of Life among Human Immunodeficiency Virus
      Infected Adults With and Without Visceral Leishmaniasis in northwest Ethiopia: A
      Longitudinal Follow-Up Study.
AB  - There has been a scarcity of data on the effect of health care on the quality of
      life (QoL) of human immunodeficiency virus (HIV)- and visceral leishmaniasis (VL)
      coinfected patients over time. We sought to assess the change that health care
      brings about in the QoL of HIV patients with and without VL and its predictors in
      6 months. A total of 465 HIV patients without VL and 125 HIV-VL-coinfected
      patients were enrolled in the longitudinal follow-up study from October 2015 to
      September 2016. Data on QoL at baseline and in 6 months were collected by trained
      nurses through face-to-face interviews using a short Amharic version of World
      Health Organization QoL instrument for HIV clients. Multiple linear regressions
      were used to assess the predictors of health-related QoL. There was an
      improvement in all of the domains of QoL at the sixth month follow-up compared
      with the baseline for both groups of patients (P < 0.001). Lack of social support
      and income were associated with the low improvement in QoL in most of the domains
      in both groups. Compared with patients having severe acute malnutrition, patients
      having moderate acute malnutrition and normal nutritional status were better in
      most of the QoL domains in both groups of patients. Both antiretroviral and anti
      VL treatments showed improvement in all dimensions of QoL. Income, social
      support, and nutritional status were the predictors for most of the QoL domains.

PMID- 29363455
TI  - Case Report: Iatrogenic Infection from Traditional Treatment of Stingray
      Envenomation.
AB  - A 47-year-old man was stung on the left ankle by a stingray while on vacation on
      the Island of Bubaque, Guinea-Bissau. The affected limb was initially treated
      with an attempt to suck out the venom and application of chewed plant root. The
      following 3 days, local pain gradually diminished, but then high fever erupted
      together with generalized symptoms and intense pain from the ankle. After
      initiating antibiotic treatment, the patient was evacuated. Because of sustained
      symptoms and fever, the wound was surgically debrided, and culture revealed
      infection with oral flora bacteria. Attempts to suck out venom are not
      recommended.

PMID- 29363456
TI  - Meta-Analyses of Japanese Encephalitis Virus Infection, Dissemination, and
      Transmission Rates in Vectors.
AB  - The objective of this work was to summarize and quantify Japanese encephalitis
      virus (JEV) infection, dissemination, and transmission rates in mosquitoes, using
      a meta-analysis approach. Data were obtained from experimental studies, gathered
      by means of a systematic review of the literature. Random-effects subgroup meta
      analysis models by mosquito species were fitted to estimate pooled estimates and
      to calculate the variance between studies for three outcomes of interest: JEV
      infection, dissemination, and transmission rates in mosquitoes. To identify
      sources of heterogeneity among studies and to assess the association between
      different predictors (mosquito species, virus administration route, incubation
      period, and diagnostic method) with the outcome JEV infection rate in vectors, we
      fitted univariable meta-regression models. Mosquito species and administration
      route represented the main sources of heterogeneity associated with JEV infection
      rate in vectors. This study provided summary effect size estimates to be used as
      reference for other investigators when assessing transmission efficiency of
      vectors and explored sources of variability for JEV infection rates in vectors.
      Because transmission efficiency, as part of vector competence assessment, is an
      important parameter when studying the relative contribution of vectors to JEV
      transmission, our findings contribute to further our knowledge, potentially
      moving us toward more informed and targeted actions to prevent and control JEV in
      both affected and susceptible regions worldwide.

PMID- 29363457
TI  - The Effectiveness of Community Bed Net Use on Malaria Parasitemia among Children
      Less Than 5 Years Old in Liberia.
AB  - In 2013, the under-5 mortality rate in Liberia was 71 deaths per 1,000 live
      births, with malaria responsible for 22% of those deaths. One of the primary
      existing control tools, long-lasting insecticide-treated bed nets (LLINs), is
      thought to be dually effective, acting as a physical barrier but also decreasing
      the mosquito population in communities. However, there has been little
      investigation into the protective effects of community-wide bed net use above and
      beyond the individual level. Using data from the population-representative 2011
      Liberia Malaria Indicator Survey, we estimated the association between proportion
      of a community using LLINs and malaria in children using multi-level logistic
      regression. To investigate the potential effect measure modification of the
      relationship by urbanicity, we included an interaction term and calculated
      stratum-specific prevalence odds ratios (PORs) for rural and urban communities.
      We calculated a POR of malaria for an absolute 10% increase in community bed net
      use of 1.13 (95% confidence interval [CI]: 0.91, 1.41) and 0.35 (95% CI: 0.13,
      0.92) for rural and urban communities, respectively, indicating a strong, though
      imprecise, protective effect within urban communities only. Our results indicate
      that bed net use has an indirect protective effect in urban areas, above and
      beyond individual use. Little or no such effect of community-wide use is seen in
      rural areas, likely because of population density factors. Therefore, although
      all control efforts should be multifaceted, promotion of bed net use in urban
      areas in particular will likely be a highly effective tool for control.

PMID- 29363458
TI  - Case Report: A Case of Colorado Tick Fever Acquired in Southwestern Saskatchewan.
AB  - Colorado tick fever virus is transmitted by Dermacentor andersoni ticks. In
      Canada, these ticks are found in the southern regions of British Columbia (Rocky
      Mountains) and Alberta, as well as southwestern Saskatchewan. Colorado tick fever
      should be clinically suspected in patients presenting with a biphasic febrile
      illness and leukopenia following tick exposure in the appropriate geographic
      area.

PMID- 29363459
TI  - cDNA Isolation and Expression of Nicotinamide Adenine Dinucleotide Phosphate
      Dependent Cytochrome P450 Reductase Gene in the Chagas Disease Vector Triatoma
      infestans.
AB  - Pyrethroid resistance has been detected in Triatoma infestans (Hemiptera:
      Reduviidae), which was atributed to target site insensitivity and increased
      oxidative metabolism of the insecticide by cytochrome P450s. Nicotinamide adenine
      dinucleotide phosphate (NADPH) cytochrome P450 reductase (CPR) plays an essential
      role in transferring electrons from NADPH to the P450-substrate complex. In this
      study, the full length CPR cDNA of T. infestans was isolated and gene expression
      was determined by quantitative polymerase chain reaction. The open reading frame
      is 2,046 bp long, encoding a protein of 682 amino acids. Amino acid sequence
      analysis indicates that the T. infestans CPR and the putative Rhodnius prolixus
      and Triatoma dimidiata CPRs present conserved ligand-binding domains. Congruent
      with a previous study of our laboratory, in which the expression of three
      cytochrome P450 genes (CYP4EM7, CYP3085B1, and CYP3092A6 genes) was induced by
      deltamethrin, the levels of T. infestans CPR mRNA were upregulated in the fat
      body of fifth instar nymphs after topical application of deltamethrin. Besides,
      as it was observed in the CYP4EM7 gene, it was detected overexpression of the CPR
      gene in the most resistant strain of T. infestans included in the study. These
      results suggest that CPR plays an essential role in P450-mediated resistance of
      T. infestans to insecticides.

PMID- 29363460
TI  - Detection of Zika Virus Infection in Myanmar.
AB  - Zika virus (ZIKV), an emerging mosquito-borne flavivirus, causes a dengue-like
      infection that has recently caught global attention. The infection, which also
      includes some birth defects, has been documented in the Americas, Pacific
      Islands, and some parts of Africa and Asia. There are no published reports on
      local ZIKV transmission in Myanmar. In this study, a total of 462 serum samples
      from patients and asymptomatic persons were collected in Myanmar from 2004 to
      2017. They were analyzed for ZIKV infection by immunoglobulin M capture enzyme
      linked immunosorbent assay (ELISA), immunoglobulin G indirect ELISA,
      neutralization test, real-time polymerase chain reaction (PCR), and conventional
      PCR. Our study confirmed ZIKV infection in 4.9% of patients with clinical dengue
      symptoms and in 8.6% of persons who were asymptomatic. This is the first report
      on ZIKV infection in Myanmar and it suggests the occurrence of ZIKV infection in
      two geographically distinct sites in this country since at least 2006.

PMID- 29363461
TI  - Trypanosoma cruzi Infection Does Not Decrease Survival or Reproduction of the
      Common Bed Bug, Cimex lectularius.
AB  - Although not presently implicated as a vector of human pathogens, the common bed
      bug, Cimex lectularius, has been suspected of carrying human pathogens because of
      its close association with humans and its obligate hematophagy. Recently, we
      characterized the vectorial competence of C. lectularius for the parasite
      Trypanosoma cruzi, the causative agent of Chagas disease. We observed that C.
      lectularius can acquire T. cruzi infection when fed on T. cruzi-carrying mice,
      and subsequently transmit T. cruzi to uninfected mice. This led us to ask why has
      C. lectularius not been implicated in the transmission of T. cruzi outside of the
      laboratory? We hypothesized that T. cruzi reduces C. lectularius fitness (i.e.,
      survival and/or reproduction) as an explanation for why C. lectularius does not
      to transmit T. cruzi in natural settings. We tested this hypothesis by comparing
      the survival and reproduction of uninfected and T. cruzi-infected C. lectularius.
      We observed that T. cruzi had a variable effect on C. lectularius survival and
      reproduction. There were negligible differences between treatments in juveniles.
      Infected adult females tended to live longer and produce more eggs. However, no
      effect was consistent, and infected bugs showed more variation in survival and
      reproduction metrics than control bugs. We did not observe any negative effects
      of T. cruzi infection on C. lectularius survival or reproduction, suggesting that
      decreased fitness in T. cruzi-infected C. lectularius is not why bed bugs have
      not been observed to transmit T. cruzi in natural settings.

PMID- 29363462
TI  - Seroprevalence of Rift Valley Fever Virus Antibodies in Cattle in Mali, 2005
      2014.
AB  - Rift Valley fever virus (RVFV) outbreaks have considerable impact on human and
      animal health. Here, we are reporting a serosurvey of cattle from all regions of
      Mali. These demonstrated that few had been exposed to RVFV from 2005 to 2014.
      Recent outbreaks of RVF in Niger and a single human case in Mali provide
      justification for further entomological and ecological studies of this virus.

PMID- 29363463
TI  - The Psychoexposome: A holistic perspective beyond health and disease.
AB  - BACKGROUND: The concept of the exposome has emerged as a new strategy for
      studying all environmental exposures throughout an individual&rsquo;s life and
      their impact on human health. Nowadays, electronic devices are available to
      collect data about an individual&rsquo;s geolocation, biological function, or
      exposure biomarkers. The appearance of &ldquo;omic&rdquo; sciences and advances
      in bioinformatics have allowed massive data-gathering and analysis from various
      scientific fields. OBJECTIVE: to propose the term Psychoexposome in line with the
      concept of the exposome from the field of environmental sciences. METHOD: a
      literature review of psychological terms associated with the exposome concept was
      carried out and the rationale and benefits of a psychoexposme approach for
      psychological sciences is discussed. RESULTS: the terms psychology, psychiatry
      and neurological diseases are scarce in the exposome approach. A long tradition
      in psychology of performing epidemiological studies and in the study of
      multifactorial influences traits places psychologists at an advantageous starting
      point for conducting psychoexposome studies. CONCLUSION: psychology may take
      advantage from both exposome and omic sciences to create an integrated
      psychoexposome approach that may help in deciphering the etiology of
      psychological disorders and improving people&rsquo;s mental health.

PMID- 29363464
TI  - Diminished emotional expression in schizophrenia: an interdisciplinary approach
      based on behavioral interventions.
AB  - BACKGROUND: Negative symptoms represent the main cause of disability in
      schizophrenia, having recently been grouped into two general dimensions:
      avolition and diminished emotional expression, which includes affective
      flattening and alogia. The aim of this study was to explore the response of these
      two symptoms to a set of behavioral interventions based on contingency
      management, performed in an interdisciplinary context. METHOD: Behaviors of
      interest were monitored and evaluations before and after the treatment were
      performed on 9 schizophrenic inpatients with persistent negative symptoms. The
      program included 12 group double sessions aimed at developing facial expression
      and verbal communication, and a nursing care plan to generalize and strengthen
      these behaviors synergistically. RESULTS: there were appreciable differences in
      facial expression, which were less clear for alogia. The clinical evaluation
      using PANSS-N did not find notable differences at group level, but the nursing
      assessment using NOC indicators did. CONCLUSIONS: although difficult to modify,
      negative symptoms are not insensitive to the influence of behavioral
      interventions. Specific psychological interventions that address negative
      symptoms as a priority focus of attention and care need to be promoted and
      developed, particularly when considering the crucial role of context in their
      progression.

PMID- 29363465
TI  - Treating anxiety and depression of cancer survivors: Behavioral activation versus
      acceptance and commitment therapy.
AB  - BACKGROUND: Behavioral activation (BA) and acceptance and commitment therapy
      (ACT) are considered particularly useful treatments when dealing with emotional
      problems of cancer survivors. The efficacy of these two treatments, applied on a
      group basis, were evaluated and compared. METHOD: An analysis was carried out of
      pre-post treatment changes in the emotional state and patterns of
      activation/avoidance of 52 cancer patients, with anxiety and/or depression,
      randomly assigned to three groups (BA/ACT/waiting list control). RESULTS: Both
      therapies were superior to no treatment in all the variables evaluated.
      Significant differences were found between the two treatments in favor of ACT in
      social impairment and avoidance/rumination. CONCLUSIONS: BA and ACT, applied on a
      group basis, are efficacious in the treatment of those emotional difficulties
      most prevalent in cancer survivors. Results suggest that activation and avoidance
      are the mechanisms responsible for the changes.

PMID- 29363466
TI  - Peer counselling versus role-playing: Two training methods of therapeutic skills
      in clinical psychology.
AB  - BACKGROUND: Training programmes for clinical psychologists should include
      evidence-based teaching methods that enable trainees to learn therapeutic skills.
      Here we compared the perceived utility of role-playing vs. peer counselling. In
      peer counselling, one student recounts a personal experience to the other, who
      thus has the opportunity to act as the therapist in relation to a real situation.
      Given that sharing such personal experiences may provoke discomfort in students,
      we also examined this aspect. METHOD: Trainees (n=202) were given both role-play
      and peer counselling activities as a way of practising empathy and active
      listening. After completing the skills training programme they completed a
      questionnaire to assess the extent to which each method had helped them to
      develop their self-awareness and to acquire these therapeutic skills. RESULTS: In
      general, peer counselling was considered more useful than role-playing for
      enhancing self-awareness and personal growth, as well as for learning these
      professional skills. Regarding the discomfort experienced by students, our data
      suggest that any initial reluctance to share personal experiences is outweighed
      by the personal and professional benefits obtained. CONCLUSIONS: Our results
      indicate that experiential learning involving emotionally charged situations is
      an effective way of teaching therapeutic skills to clinical and health psychology
      trainees.

PMID- 29363467
TI  - Health-related quality of life among smoking relapsers.
AB  - BACKGROUND: Previous studies have shown that smoking is associated with health
      related quality of life (HRQoL) impairment. In order to evaluate HRQoL in a
      sample of Spanish relapsers, a cross-sectional study was conducted. METHOD: The
      sample was made up of 775 smokers who had relapsed after a period of abstinence.
      HRQoL was evaluated using the Euro-Qol questionnaire (EQ-5D); through the
      descriptive profile, the EQ-5D index and the visual analogue scale (EQ-VAS).
      RESULTS: Higher nicotine dependence was related to worse HRQL. According to the
      EQ-VAS, higher daily cigarette consumption and more years smoking were related to
      worse perceived health. In the EQ-5D those who had quit smoking in the previous
      year perceived worse health. Mobility and anxiety / depression are the dimensions
      affected by smoking. Those who are more nicotine dependent (OR = 2.29) and have
      been smoking for longer (OR = 4.12) are more likely to have mobility problems;
      and those who are nicotine dependent (OR = 1.85) and relapsed more than a year
      ago (OR = 0.63), are more likely to experience anxiety / depression. CONCLUSIONS:
      Nicotine dependence demonstrated a determining effect on HRQOL deterioration in
      smokers who have relapsed.

PMID- 29363468
TI  - Are previous suicide attempts a risk factor for completed suicide?
AB  - BACKGROUND: A previous suicide attempt is a clinically relevant factor for
      completed suicide. In this paper people who committed suicide on their first
      attempt are compared with those who did so after previous attempts. METHOD: A
      review of the Computerised Clinical Histories in the Navarro Health Service
      Osasunbidea (2010-2013) in Spain. RESULTS: Of the 166 cases, 31.9% (n = 53)
      presented at least one prior attempt. Of these 53, 65.3% modified the method of
      suicide. Women presented significantly more attempts (&chi;2 = 14.3; df = 3; p =
      .002). Three sub-samples were identified according to the attempts and diagnoses.
      The diagnoses of personality disorders (90.9%; n = 10) and women under 51 years
      of age with a diagnosis of affective, anxiety, or substance abuse disorders
      (82.4%; n = 14) presented the highest numbers of attempts. People without a
      psychiatric diagnosis and with psychotic or organic mental disorders presented
      the smallest proportion of attempts (13.2%; n = 10) together with people over 51
      years of age diagnosed with affective, anxiety, or substance abuse disorders
      (22.5%; n = 9). CONCLUSIONS: Prior attempts are suicide risk factors only in
      specific clinical sub-samples. Prevention and intervention programs should
      consider these results.

PMID- 29363470
TI  - Understanding olympic champions and their achievement goal orientation, dominance
      and pursuit and motivational regulations: A case study.
AB  - BACKGROUND: The goal was to compare the achievement goal profile and the
      motivational regulations of one world-class and two high-level athletes during
      their preparation for the Rio Olympic Games. METHOD: Three kayakers from the
      Spanish Olympic team participated. One (P1) and two (P2) were high-level
      athletes: finalists at the World and European championships, and several national
      championships. Participant three (P3) was a world-class athlete: 2 Olympic
      medals, 7 World championship medals, 4 European championship medals, and several
      national championships. Before and after three training sessions and 4
      international competitions (including World and European championships) all
      participants completed a questionnaire to assess their achievement goal
      orientation, dominance and pursuit, as well as their motivational regulation.
      Generalized estimated equations (GEE) analysis was used to assess significant
      differences between subjects. RESULTS: P3 had lower performance-approach goal
      orientation, stronger mastery-approach goal dominance, lower performance-approach
      and performance-avoidance goal pursuit, higher mastery-avoidance goal pursuit and
      lower controlled motivation than the other two participants. CONCLUSION: Our
      world-class athlete has a strong mastery-approach achievement goal dominant
      profile, and a low performance-oriented profile (both approach and avoidance) and
      controlled motivation. This profile should be confirmed in similar athletes to
      help coaches and their young athletes make appropriate decisions.

PMID- 29363469
TI  - Psychoeducational assessment of students with intellectual disability:
      professional-action framework analysis.
AB  - BACKGROUND: The right to educational inclusion for students with intellectual
      disability (SWID) requires the development of good assessment and intervention
      practices from holistic perspectives not exclusively focused on the academic
      limitations that SWID may present. These practices are settled in Spain, via
      regulations drawn up by each Autonomous Community (AC). The variety of existing
      regulations demands a critical review of the decisions taken to promote the
      inclusion of those students. METHOD: current regulations-in-force in each AC that
      regulate attention to diversity (AD) have been were analyzed by using a checklist
      that includes the variables that defining each stage of the AD process and the
      ways of providing supports that favor the development, learning and participation
      of SWID. RESULTS: attention to diversity measures in each AC emphasize
      organizational and curricular issues, with no AC following holistic approaches in
      both assessment and intervention, but rather neglecting self-determination and
      the promotion of quality of life for SWID. CONCLUSIONS: guidelines for the
      development of new legal frameworks and professional practices based on the
      latest evidence-based models of attention to SWID and on the results are
      discussed.

PMID- 29363471
TI  - Defensive pessimism, self-esteem and achievement goals: A person-centered
      approach.
AB  - BACKGROUND: The relationship between defensive pessimism, self-esteem, and
      achievement goals is a controversial issue. The main contribution of this
      research is the adoption of a person-centered approach to explore the existence
      of differentiated profiles of university students, which combine self-esteem and
      defensive pessimism. In addition, we analyze whether these profiles differ in
      their achievement goals (learning, performance-approach, performance-avoidance,
      and work-avoidance). METHOD: 1,028 university students took part in the study.
      RESULTS: Four student profiles were identified: (a) HSE/MDP (high self-esteem and
      moderate defensive pessimism); (b) LSE/LDP (low self-esteem and low defensive
      pessimism); (c) HSE/LDP (high self-esteem and low defensive pessimism); and (d)
      LSE/HDP (low self-esteem and high defensive pessimism). These four profiles
      differ significantly in their achievement goals. CONCLUSIONS: The use of
      defensive pessimism may involve students with either low or high self-esteem,
      although the two profiles follow differentiated motivational achievement
      trajectories.

PMID- 29363472
TI  - Dimensions of parenting styles, social climate, and bullying victims in primary
      and secondary education.
AB  - BACKGROUND: Bullying as a construct is found to be related to a variety of
      individual, parental and academic factors. Familial factors include family
      environment, parenting style and parental involvement. The main aim of this study
      is to find out how Primary and Secondary Education students perceive parenting
      styles and social climate and if there are differences between pupils from these
      two educational stages. The study also considers the relationship between these
      perceptions of bullying victims and certain peer socio-affective factors. METHOD:
      Participants were 847 children and adolescents. School social climate and Family
      social climate were both evaluated using the Spanish version of Moos&rsquo;
      Family Social Climate Scale, and Parenting styles were evaluated according to the
      Parental Socialization Scale in Adolescence (ESPA29). Roles associated with
      bullying, and correlates of social reputation were measured using the Bull-S
      questionnaire. RESULTS: There are differences in how primary and secondary
      education students perceive parenting styles and family climate. CONCLUSIONS:
      Parental factors are related to bullying victimization and socio-affective group
      variables (social preference, acceptance or rejection levels, and the number of
      friends). The study highlighs risk and protective factors for victimization.

PMID- 29363473
TI  - Aggressive behavior in adolescence as a predictor of personal, family, and school
      adjustment problems.
AB  - BACKGROUND: The goal of the present study was to determine the extent to which
      aggressive behavior towards peers predicts greater personal, school, and family
      maladjustment in adolescent aggressors of both sexes. METHOD: The sample
      consisted of 1510 Spanish adolescents from 12 to 17 years old, who anonymously
      and voluntarily completed self-report questionnaires. RESULTS: Binary Logistic
      regression analysis showed that, regarding personal adjustment, aggressive
      behavior was significantly associated with high scores in depressive
      symptomatology, perceived stress and loneliness, and low scores in self-esteem,
      life satisfaction and empathy, for both sexes. In the school setting, aggressive
      behavior was related to low scores in academic engagement, friends in the
      classroom, perception of teacher support, and a positive attitude towards school.
      At the family level, significant relationships were observed between aggressive
      behavior and high scores in offensive communication and family conflict, and low
      scores in open communication with parents, general expressiveness, and family
      cohesion. CONCLUSIONS: In cases of peer violence it is necessary to give urgent
      attention to all those involved, since maladjustment in aggressors can be
      predicted in many levels of intervention.

PMID- 29363474
TI  - Evidence supporting need satisfaction and frustration as two distinguishable
      constructs.
AB  - BACKGROUND: This paper aims to (1) investigate whether psychological need
      satisfaction and frustration are distinguishable constructs or part of a single
      continuum, and (2) to develop and validate the Spanish version of the Need
      Satisfaction and Frustration Scale (NSFS). METHOD: Confirmatory factor analysis
      (CFA) and exploratory structural equation models (ESEM) were tested using three
      samples ( N total = 959). RESULTS: In all samples, a CFA model specifying
      satisfaction and frustration of each psychological need as distinguishable
      constructs fit the data better than models specifying them as part of a
      continuum, even after including method corrections (CFA) or cross-loadings
      (ESEM). Scale score reliabilities were adequate only when the satisfaction and
      frustration of each need were treated as distinguishable constructs. CONCLUSIONS:
      The paper provides strong support for specifying need satisfaction and
      frustration as distinguishable but correlated constructs, as well as adequate
      evidence of dimensionality, reliability and criterion validity for the Spanish
      version of the NSFS.

PMID- 29363475
TI  - Moral emotions associated with prosocial and antisocial behavior in school-aged
      children.
AB  - BACKGROUND: The present study aims to explore the main effects and interactive
      effects of empathy, guilt, shame, pride (authentic and hubristic), and moral
      pride, on prosocial and antisocial behavior in children. METHOD: The sample group
      comprised 351 children aged between 10 and 14 selected from four schools in the
      Basque Country (Spain). Hierarchical multiple regression models were used in the
      statistical analyses. RESULTS: Prosocial behavior was found to be predicted by
      the additive interaction between empathy and moral pride, by guilt and, to a
      lesser extent and negatively, by shame. In relation to antisocial behavior,
      children with a strong disposition to guilt scored lower for antisocial behavior,
      regardless of their empathy levels. Nevertheless, the combination of low empathy
      and low guilt levels was associated with highest antisocial behavior scores. As
      regards shame, this emotion was moderately associated with antisocial behavior.
      CONCLUSIONS: By exploring interactions the present study provided a more nuanced
      view of the emotional factors associated with children&acute;s prosocial and
      antisocial behavior.

PMID- 29363476
TI  - The effects of work engagement and self-efficacy on personal initiative and
      performance.
AB  - BACKGROUND: Two popular concepts, work engagement and personal initiative, are
      different but related constructs. This study is based on and extends the Frese
      and Fay (2001) model of personal initiative (PI) by including work engagement
      (WE) and self-efficacy as antecedents of PI, and performance as a consequence.
      METHOD: Two studies (study 1, with a cross-sectional design using N = 396
      participants from 22 organizations, and study 2, with a longitudinal design
      conducted in two waves with N = 118 participants from 15 organizations) test the
      hypotheses. RESULTS: Structural equation modeling and the PROCESS SPSS Macro were
      used to test the hypothesized mediating role of personal initiative in work
      engagement and performance, and the results show the indirect effect of WE on
      performance through PI. CONCLUSIONS: The results of these two studies confirmed
      our hypotheses: WE and self-efficacy lead to higher PI, which, in turn, leads to
      higher performance. In addition to considering WE as an antecedent of PI, the
      results lead to considering PI as an antecedent of performance.

PMID- 29363477
TI  - Empathy by default: Correlates in the brain at rest.
AB  - BACKGROUND: Empathy, defined as the ability to access and respond to the inner
      world of another person, is a multidimensional construct involving cognitive,
      emotional and self-regulatory mechanisms. Neuroimaging studies report that
      empathy recruits brain regions which are part of the social cognition network.
      Among the different resting state networks, the Default Mode Network (DMN) may be
      of particular interest for the study of empathy since it has been implicated in
      social cognition tasks. METHOD: The current study compared the cognitive and
      emotional empathy scores, as measured by the Interpersonal Reactivity Index, with
      the patterns of activation within the DMN, through the neuroimaging methodology
      of resting-state functional magnetic resonance. RESULTS: Results suggest a
      significant positive correlation between cognitive empathy and activation of the
      bilateral superior medial frontal cortex nodes of the DMN. Contrastingly, a
      negative correlation was found between emotional empathy and the same brain
      region. CONCLUSIONS: Overall, this data highlights a critical role of the medial
      cortical regions of the DMN, specifically its anterior node, for both cognitive
      and emotional domains of the empathic process.

PMID- 29363478
TI  - Differential Item Functioning: Beyond validity evidence based on internal
      structure.
AB  - BACKGROUND: In the latest release of the Standards for Educational and
      Psychological Testing, Differential Item Functioning (DIF) is considered as
      validity evidence based on internal structure. However, there are no indications
      of how to design a DIF study as a validation study. In this paper, we propose
      relating DIF to all sources of validity evidence, and provide a general
      conceptual framework for transforming &ldquo;typical&rdquo; DIF studies into
      validation studies. METHOD: We perform a comprehensive review of the literature
      and make theoretical and practical proposals. RESULTS: The article provides
      arguments in favour of addressing DIF detection and interpretation as validation
      studies, and suggestions for conducting DIF validation studies. DISCUSSION: The
      combination of quantitative and qualitative data within a mixed methods research
      perspective, along with planning DIF studies as validation studies, can help
      improve the validity of test score interpretations.

PMID- 29363479
TI  - Deciding on Null Hypotheses using P-values or Bayesian alternatives: A simulation
      study.
AB  - BACKGROUND: The p-value is currently one of the key elements for testing
      statistical hypothesis despite its critics. Bayesian statistics and Bayes Factors
      have been proposed as alternatives to improve the scientific decision making when
      testing a hypothesis. This study compares the performance of two Bayes Factor
      estimations (the BIC-based Bayes Factor and the Vovk-Sellke p-value calibration)
      with the p-value when the null hypothesis holds. METHOD: A million pairs of
      independent data sets were simulated. All simulated data came from a normal
      population and different sample sizes were considered. Exact p-values for
      comparing sample means were recorded for each sample pair as well as Bayesian
      alternatives. RESULTS: Bayes factors exhibit better performance than the p-value,
      favouring the null hypothesis over the alternative. The BIC-based Bayes Factor is
      more accurate than the p-value calibration under the simulation conditions and
      this behaviour improves as the sample size grows. CONCLUSIONS: Our results show
      that Bayesian factors are good complements for testing a hypothesis. The use of
      the Bayesian alternatives we have tested could help researchers avoid claiming
      false statistical discoveries. We suggest using classical and Bayesian statistics
      together instead of rejecting either of them.

PMID- 29363480
TI  - Development and validation of a questionnaire for assessing the characteristics
      of diet and physical activity in patients with type 2 diabetes.
AB  - BACKGROUND: The aim ofthis study was to explore the psychometric properties of
      the Motiva.Diaf-DM2 questionnaire, which assesses adherence to a healthy diet and
      physical activity in patients with Type 2 Diabetes (T2D). METHOD: Participants
      were 206 patients who attended primary care services, with a mean age of 69.63
      years (SD = 11.05), with 39.3% of the participants being women. To assess the
      test-retest reliability of the measure, a random subsample (n = 40) of patients
      who had another appointment scheduled was selected to fill in the questionnaire
      once again two weeks after the initial administration. RESULTS: The reliability
      of the scores was found to be appropriate both in terms of internal consistency
      (&alpha; first factor = .756; &alpha; second factor = .821) and temporal
      stability (r first factor = .604; r second factor = .638). The structure of the
      test is two-dimensional. The scores for the second dimension (adherence to
      physical activity) are in agreement with the scores for basic psychological needs
      (r physical activity = .281), resilience (r = .216), and glycated haemoglobin (r
      = -.182). CONCLUSIONS: The Motiva.Diaf-DM2 test was shown to have the appropriate
      relia-bility and validity to assess adherence to a healthy diet and physical
      activity in patients diagnosed with T2D.

PMID- 29363481
TI  - Adaptation of the Test of Performance Strategies Competition Subscale to Spanish.
AB  - BACKGROUND: In recent years, there has been a growing interest in the
      conceptualisation and assessment of athletes&rsquo; psychological skills and the
      study of their impact on sports performance. The aim of this study was to adapt
      the Test of Performance Strategies 3 competition subscale to the Spanish context.
      METHOD: The items included in the original test in English were translated using
      a double-back method, and the test was completed by a sample of 1,003 Spanish
      athletes of both sexes. Analyses of the factorial validity, reliability and
      invariance of the measurement model were carried out. RESULTS: Favourable
      evidence was obtained for a measurement model comprising 36 items grouped in 9
      factors, similar to the original model. Model fit was reasonable for both
      individual parameters and overall. Reliability rates were satisfactory for the
      overall test and for each factor. Evidence was also favourable for sex-based
      measurement model invariance. CONCLUSIONS: The adaptation is satisfactory and fit
      for use by sports psychology researchers and professionals in assessing the
      psychological skills employed by athletes in competition.

PMID- 29363482
TI  - Validation of the Child PTSD Symptom Scale (CPSS) in Spanish adolescents.
AB  - BACKGROUND: One of the most frequently used instruments to assess posttraumatic
      stress in children and adolescents is the Child PTSD Symptom Scale. However,
      there has been limited evaluation of its construct validity in the Spanish
      language despite Spanish being one of the most widely spoken languages in the
      world. OBJECTIVE: To provide data on the psychometric properties of the CPSS in a
      sample of Spanish adolescents, to establish the internal consistency of the
      measure, and to examine its criterion validity. METHOD: The participants were 339
      adolescents (172 boys and 167 girls, mean age 13.95) exposed to peer violence
      during the previous year. RESULTS: Confirmatory factor analysis demonstrated a
      good fit to the four-factor dysphoria model. The alpha reliabilities for the
      overall measure and its subscales were suitable. DISCUSSION: The Spanish version
      of the scale has sound psychometric properties with good reliability and
      validity. Moreover, it integrates the four-factor structure corresponding to the
      dimensions of PTSD described in the DSM-V.

PMID- 29363483
TI  - The Spanish version of the Job Crafting Scale.
AB  - BACKGROUND: A literature review reveals that there is no measure of job crafting
      available in Spanish. This paper presents the translation, adaptation and
      validation of a scale to measure job crafting behaviors (i.e. the Spanish Job
      Crafting Scale &ndash; SJCS; Tims, Bakker, & Derks, 2012). METHODS: The scale was
      applied to a sample of 896 employees in Spain (52.26% women and 47.4% men). We
      tested the reliability and factorial validity of the 21-item instrument. RESULTS:
      After confirmatory factor analysis (CFI=.858, TLI= .838, IFI= .860, RMSEA= .067),
      the results show a structure consisting of four factors: Increasing structural
      job resources; Decreasing hindering job demands; Increasing social job resources;
      Increasing challenging job demands. These four factors demonstrate adequate
      reliability and evidence of validity with others scales that refer to Engagement
      at Work and Proactivity. CONCLUSION: The questionnaire may be a useful tool for
      the assessment of job crafting and for future research in Spanish speaking
      countries.

PMID- 29363484
TI  - The comparison of the degree of apoptosis in ovaries and fallopian tubes between
      two different surgical interventions for tubal ligation: A rat model.
AB  - OBJECTIVE: To compare the degree of apoptosis in ovaries and tubal epithelium
      observed secondary to tubal ligation either by Pomeroy's method or bipolar
      electrocauterization in a rat model. MATERIAL AND METHODS: A total of 24 female
      Sprague-Dawley rats were randomly assigned into 3 study groups: control (n=8),
      Pomeroy (n=8), and the electrocauterization group (n=8). Apoptotic cells were
      detected on the primary, secondary, tertiary follicles of the ovaries, and on the
      tubal epithelium using terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labeling. The apoptotic index was calculated
      for each group by the percentage of the stained cells. RESULTS: The apoptotic
      index of tubal epithelium was significantly higher in the bipolar
      electrocauterization group compared with the control and Pomeroy groups (3.1+/
      0.8 vs. 1.4+/-1.0, p=0.018 and 2.0+/-1.2, p=0.03, respectively) whereas there was
      no significant difference between Pomeroy's method and the control group. The
      apoptotic index of primary follicles was higher in the bipolar
      electrocauterization group compared with the control and Pomeroy's method groups
      (3.4+/-0.5 vs. 1.2+/-0.4, p<0.001 and 1.8+/-0.8, p=0.005, respectively), but
      there was no significant difference between Pomeroy's method and the control
      group. The apoptotic index of secondary and tertiary follicles was similar for
      each group. CONCLUSION: Pomeroy's technique, as a permanent contraception method,
      is associated with lower apoptotic index on ovary and fallopian tube when
      compared with bipolar electrocauterization.

PMID- 29363485
TI  - Effect and Mechanism of EGFL7 Downregulation in Human Osteosarcoma Cells on the
      Biological Function of Co-cultured HUVEC.
AB  - BACKGROUND: Even though epidermal growth factor-like domain 7 is known to be
      overexpressed in osteosarcoma and is associated with poor clinical outcome, few
      reports are available regarding its mechanism. AIMS: The objective of this study
      was to explore the effect and mechanism of downregulating epidermal growth factor
      like domain 7 expression in a human osteosarcoma cell line on the biological
      function of co-cultured human umbilical vein endothelial cells. STUDY DESIGN:
      Cell study. METHODS: In the present study, human osteosarcoma cell lines U2OS,
      Saos-2, HOS, and MG63, and normal human osteoblasts were cultured in Dulbecco's
      Modified Eagle Medium containing 10% fetal bovine serum and 1x antibiotics at 37 
      degrees C and 5% CO2 in an incubator. Of the four osteosarcoma cell lines, U2OS
      expresses the highest level of epidermal growth factor-like domain 7 mRNA as
      determined using quantitative reverse transcription polymerase chain reaction.
      With the knockdown of epidermal growth factor-like domain 7 in U2OS and human
      umbilical vein endothelial cells by lentivirus, the proliferation and apoptosis
      of U2OS and human umbilical vein endothelial cells were investigated using MTT
      and flow cytometry assays. After the co-culture of human umbilical vein
      endothelial cells and epidermal growth factor-like domain 7-knockdown U2OS, the
      in vitro effects on cell proliferation, apoptosis, adhesion, migration, and the
      angiogenic ability of human umbilical vein endothelial cells were detected using
      MTT, flow cytometry, Transwell, and tube formation assays, respectively. The
      expressions of phosphoinositide 3-kinase, phospho-Akt, total Akt, and vascular
      endothelial growth factor in human umbilical vein endothelial cells were detected
      using western blot assay. RESULTS: Lentivirus with epidermal growth factor-like
      domain 7 shRNA could not significantly affect the proliferation and apoptosis of
      both U2OS and human umbilical vein endothelial cells, whereas the knockdown of
      epidermal growth factor-like domain 7 in U2OS could significantly inhibit the
      migration, adhesion, and angiogenic ability of co-cultured human umbilical vein
      endothelial cells. In addition, the expressions of phosphoinositide 3-kinase,
      phospho-Akt, and vascular endothelial growth factor in human umbilical vein
      endothelial cells decreased after co-culturing with epidermal growth factor-like
      domain 7-knockdown U2OS. CONCLUSION: Epidermal growth factor-like domain 7
      knockdown U2OS cells inhibit the migration, adhesion, and angiogenesis of co
      cultured human umbilical vein endothelial cells by diminishing phosphoinositide 3
      kinase, Akt signaling pathway activity and vascular endothelial growth factor
      expression.

PMID- 29363486
TI  - Highlights and future directions from the European Gynecological Oncology
      Congress 2017

PMID- 29363488
TI  - Passing information to immigration officials undermines patient confidence, MPs
      hear.

PMID- 29363489
TI  - Cell-cell signaling in blood vessel development and function.
AB  - The blood vasculature is an organ pervading all other organs (almost). During
      vascular development, cell-cell signaling by extracellular ligands and cell
      surface receptors ensure that new vessels sprout into non-vascularized regions
      and simultaneously acquire organ-specific specializations and adaptations that
      match the local physiological needs. The vessels thereby specialize in their
      permeability, molecular transport between blood and tissue, and ability to
      regulate blood flow on demand. Over the past decades, we have learnt about the
      generic cell-cell signaling mechanisms governing angiogenic sprouting, mural cell
      recruitment, and vascular remodeling, and we have obtained the first insights
      into signals that induce and maintain vascular organotypicity. However, intra
      organ vascular diversity and arterio-venous hierarchies complicate the molecular
      characterization of the vasculature's cellular building blocks. Single-cell RNA
      sequencing provides a way forward, as it allows elucidation at a genome-wide and
      quantitative level of the transcriptional diversity occurring within the same
      cell types at different anatomical positions and levels of arterio-venous
      hierarchy in the organs. In this Louis-Jeantet Prize Winner: Commentary, I give a
      brief overview of vascular development and how recent advances in the field pave
      the way for more systematic efforts to explore vascular functions in health and
      disease.

PMID- 29363490
TI  - Dissecting human antibody responses: useful, basic and surprising findings.
AB  - Human memory B cells and plasma cells represent a rich source of antibodies that
      have been selected in response to human pathogens. In the last decade, different
      methods have been developed to interrogate the human memory repertoire and
      isolate monoclonal antibodies. I will discuss how a target-agnostic approach
      based on high-throughput screening of antibodies produced by cultured B cells and
      plasma cells has not only provided potent and broadly neutralizing antibodies
      against a range of pathogens, but has also advanced our understanding of basic
      aspects of the immune response, from host-pathogen interaction to the role of
      somatic mutations in affinity maturation and in the diversification of the
      antibody response. Most surprisingly, this approach has also revealed a new
      mechanism of diversification based on templated insertion of non-Ig DNA into
      antibody genes that we discovered in the context of the immune response to
      malaria infection.

PMID- 29363491
TI  - Healthcare costs attributable to congenital cytomegalovirus infection.
AB  - OBJECTIVE: Congenital cytomegalovirus infection (cCMV) can cause symptoms at
      birth as well as long-term impairment. This study estimates cCMV-related
      healthcare costs in the Netherlands in early childhood. DESIGN, SETTING AND
      PATIENTS: In a nationwide retrospective cohort study, 156 children with cCMV were
      identified by testing 31 484 neonatal dried blood spots for cCMV. Use of
      healthcare resources in the first 6 years of life by children with cCMV and a
      matched cCMV-negative control group were analysed. Mean costs per child were
      calculated by multiplying healthcare resource use by its reference prices.
      EXPOSURE: Children with cCMV were compared with cCMV-negative children. MAIN
      OUTCOME MEASURES: The average total healthcare costs per child were based on the
      average costs for hospital admissions and consultations by healthcare providers.
      RESULTS: Mean healthcare costs of children with cCMV (?6113, n=133) were higher
      than children without cCMV (?3570, n=274), although statistically not
      significant, with a mean difference of ?2544 (95% CI ?-451 to ?5538). The costs
      of children with long-term impairment were two times higher in children with cCMV
      (?17 205) compared with children without cCMV (?8332). CONCLUSIONS: Children with
      cCMV, especially those with long-term impairment and those symptomatic at birth,
      accrue higher healthcare costs than cCMV-negative children in the first 6 years
      of life, although this is not statistically significant. This economic impact is
      of importance in the evaluation of preventive measures against cCMV. TRIAL
      REGISTRATION NUMBER: NTR3582.

PMID- 29363492
TI  - Hairy tongue in a 1-month-old infant.

PMID- 29363493
TI  - Fifteen-minute consultation: Asking questions: the puzzles and problems model.
AB  - People are full of useful advice, especially when you make the transition to the
      senior doctor grade. We present a very helpful model we have used over some time
      to aid us when we have issues.

PMID- 29363494
TI  - Learning, activity... and injury? Caring for young athletes through appropriately
      designed modified (developmental) sport.

PMID- 29363495
TI  - Preventing hamstring injuries in football through enhanced exercise and RTP
      strategies.

PMID- 29363496
TI  - Hamstring injuries are increasing in men's professional football: every cloud has
      a silver lining?

PMID- 29363497
TI  - Poor hospital design has an impact on staff, patients, and healthcare.

PMID- 29363498
TI  - A Novel In Vitro Experimental System for the Evaluation of Drug Metabolism:
      Cofactor-Supplemented Permeabilized Cryopreserved Human Hepatocytes (MetMax
      Cryopreserved Human Hepatocytes).
AB  - We report here a novel experimental system, cryopreserved MetMax human
      hepatocytes (MMHHs), for in vitro drug metabolism studies. MMHHs consist of
      cofactor-supplemented permeabilized cryopreserved human hepatocytes. The use
      procedures for MMHHs are significantly simplified from that for conventional
      cryopreserved human hepatocytes (CCHHs): 1) storage at -80 degrees C instead of
      in liquid nitrogen and 2) usage directly after thawing without centrifugation and
      microscopic evaluation of cell density and viability and cell density adjustment.
      In this study, we compared MMHHs and CCHHs in CYP1A2, CYP2A6, CYP2B6, CYP2C8,
      CYP2C9, CYP2D6, CYP2E1, CYP3A4, CYP2J2, monoamine oxidase A, aldehyde oxidase,
      flavin-containing monooxygenase, UDP-glucuronyl transferase, SULT, N
      acetyltransferase 1, and acetaminophen glutathione (GSH) conjugation activities
      based on liquid chromatography-tandem mass spectrometry quantification of
      substrate metabolism. MMHHs were prepared from CCHHs consisting of hepatocytes
      pooled from 10 individual donors. The drug metabolizing enzyme activities of both
      CCHHs and MMHHs were cell concentration and time dependent, with specific
      activities of MMHHs ranging from 27.2% (carboxylesterase 2) to 234.2%
      (acetaminophen GSH conjugation) of that for CCHHs. As observed in CCHHs,
      sequential oxidation and conjugation was observed in MMHHs for coumarin, 7
      ethoxycoumarin, and acetaminophen. 7-Hydroxycoumarin conjugation results showed
      that metabolic pathways in MMHHs could be selected via the choice of cofactors,
      with glucuronidation but not sulfation observed in the presence of UDP-glucuronic
      acid and not 3-phosphoadenosine-5-phosphosulfate, and vice versa. Results with
      noncytotoxic and cytotoxic concentrations of acetaminophen showed that drug
      metabolism was compromised in CCHHs but not in MMHHs. Our results suggest that
      the MMHHs system represents a convenient and robust in vitro experimental system
      for the evaluation of drug metabolism.

PMID- 29363499
TI  - Metabolic Profiling of the Novel Hypoxia-Inducible Factor 2alpha Inhibitor PT2385
      In Vivo and In Vitro.
AB  - PT2385 is a first-in-class, selective small-molecule inhibitor of hypoxia
      inducible factor-2alpha (HIF-2alpha) developed for the treatment of advanced
      clear cell renal cell carcinoma. Preclinical results demonstrated that PT2385 has
      potent antitumor efficacy in mouse xenograft models of kidney cancer. It also has
      activity toward metabolic disease in a mouse model. However, no metabolism data
      are currently publically available. It is of great importance to characterize the
      metabolism of PT2385 and identify its effect on systemic homeostasis in mice.
      High-resolution mass spectrometry-based metabolomics was performed to profile the
      biotransformation of PT2385 and PT2385-induced changes in endogenous metabolites.
      Liver microsomes and recombinant drug-metabolizing enzymes were used to determine
      the mechanism of PT2385 metabolism. Real-time polymerase chain reaction analysis
      was employed to investigate the reason for the PT2385-induced bile acid
      dysregulation. A total of 12 metabolites of PT2385 was characterized, generated
      from hydroxylation (M1, M2), dihydroxylation and desaturation (M3, M4), oxidative
      defluorination (M7), glucuronidation (M8), N-acetylcysteine conjugation (M9), and
      secondary methylation (M5, M6) and glucuronidation (M10, M11, and M12). CYP2C19
      was the major contributor to the formation of M1, M2, and M7, UGT2B17 to M8, and
      UGT1A1/3 to M10-M12. The bile acid metabolites taurocholic acid and tauro-beta
      muricholic acid were elevated in serum and liver of mice after PT2385 treatment.
      Gene expression analysis further revealed that intestinal HIF-2alpha inhibition
      by PT2385 treatment upregulated the hepatic expression of CYP7A1, the rate
      limiting enzyme in bile acid synthesis. This study provides metabolic data and an
      important reference basis for the safety evaluation and rational clinical
      application of PT2385.

PMID- 29363501
TI  - From cost cutting to conversation: how two CCGs and a hospitals trust turned
      financial deficit into communication bonus.

PMID- 29363500
TI  - Partnerships for child health: capitalising on links between the sustainable
      development goals.

PMID- 29363502
TI  - Prevention of bronchopulmonary dysplasia in extremely low gestational age
      neonates: current evidence.
AB  - Bronchopulmonary dysplasia (BPD) is one of the most frequent complications in
      extremely low gestational age neonates, but has remained largely unchanged in
      rate. We reviewed data on BPD prevention focusing on recent meta-analyses.
      Interventions with proven effectiveness in reducing BPD include the primary use
      of non-invasive respiratory support, the application of surfactant without
      endotracheal ventilation and the use of volume-targeted ventilation in infants
      requiring endotracheal intubation. Following extubation, synchronised nasal
      ventilation is more effective than continuous positive airway pressure in
      reducing BPD. Pharmacologically, commencing caffeine citrate on postnatal day 1
      or 2 seems more effective than a later start. Applying intramuscular vitamin A
      for the first 4 weeks reduces BPD, but is expensive and painful and thus not
      widely used. Low-dose hydrocortisone for the first 10 days prevents BPD, but was
      associated with almost twice as many cases of late-onset sepsis in infants born
      at 24-25 weeks' gestation. Inhaled corticosteroids, despite reducing BPD, were
      associated with a higher mortality rate. Administering dexamethasone to infants
      still requiring mechanical ventilation around postnatal weeks 2-3 may represent
      the best trade-off between restricting steroids to infants at risk of BPD while
      still affording high efficacy. Finally, identifying infants colonised with
      ureaplasma and treating those requiring intubation and mechanical ventilation
      with azithromycin is another promising approach to BPD prevention. Further
      interventions yet only backed by cohort studies include exclusive breastmilk
      feeding and a better prevention of nosocomial infections.

PMID- 29363505
TI  - David Oliver: What's wrong with being honest with the public about NHS pressures?

PMID- 29363504
TI  - Tinea faciei in a very preterm infant.

PMID- 29363507
TI  - FDA to begin releasing clinical study reports in pilot programme.

PMID- 29363508
TI  - Drug companies are starting to tackle antimicrobial resistance but could do more,
      report shows.

PMID- 29363506
TI  - Chk1 and 14-3-3 proteins inhibit atypical E2Fs to prevent a permanent cell cycle
      arrest.
AB  - The atypical E2Fs, E2F7 and E2F8, act as potent transcriptional repressors of DNA
      replication genes providing them with the ability to induce a permanent S-phase
      arrest and suppress tumorigenesis. Surprisingly in human cancer, transcript
      levels of atypical E2Fs are frequently elevated in proliferating cancer cells,
      suggesting that the tumor suppressor functions of atypical E2Fs might be
      inhibited through unknown post-translational mechanisms. Here, we show that
      atypical E2Fs can be directly phosphorylated by checkpoint kinase 1 (Chk1) to
      prevent a permanent cell cycle arrest. We found that 14-3-3 protein isoforms
      interact with both E2Fs in a Chk1-dependent manner. Strikingly, Chk1
      phosphorylation and 14-3-3-binding did not relocate or degrade atypical E2Fs, but
      instead, 14-3-3 is recruited to E2F7/8 target gene promoters to possibly
      interfere with transcription. We observed that high levels of 14-3-3 strongly
      correlate with upregulated transcription of atypical E2F target genes in human
      cancer. Thus, we reveal that Chk1 and 14-3-3 proteins cooperate to inactivate the
      transcriptional repressor functions of atypical E2Fs. This mechanism might be of
      particular importance to cancer cells, since they are exposed frequently to DNA
      damaging therapeutic reagents.

PMID- 29363509
TI  - Elephant in the room.

PMID- 29363510
TI  - Performance characteristics of rheumatoid factor and anti-cyclic citrullinated
      peptide antibody assays may impact ACR/EULAR classification of rheumatoid
      arthritis.
AB  - OBJECTIVES: Rheumatoid factor (RF) and anti-cyclic citrullinated protein/peptide
      antibodies (ACPA) are integrated in the 2010 American College of
      Rheumatology/European League Against Rheumatism (ACR/EULAR) classification
      criteria for rheumatoid arthritis (RA). The objectives of this study were to
      evaluate the technical and diagnostic performance of different RF and ACPA assays
      and to evaluate whether differences in performance impact RA classification.
      METHODS: Samples from 594 consecutive patients who for the first time consulted a
      rheumatologist (44 of whom were diagnosed with RA) and 26 extra newly diagnosed
      patients with RA were analysed with six different RF assays (Menarini, Thermo
      Fisher, Inova, Roche, Abbott, Euroimmun) and seven different ACPA assays
      (Menarini, Thermo Fisher, Inova, Roche, Abbott, Euro Diagnostica, Euroimmun).
      RESULTS: We found differences in analytical performance between assays. There was
      poor numerical agreement between the different RF and ACPA assays. For all
      assays, the likelihood ratio for RA increased with increasing antibody levels.
      The areas under the curve of receiver operating characteristic analysis of the RF
      (range 0.676-0.709) and ACPA assays (range 0.672-0.769) only differed between
      some ACPA assays. Nevertheless, using the cut-off proposed by the manufacturer,
      there was a large variation in sensitivity and specificity between assays (mainly
      for RF). Consequently, depending on the assay used, a subgroup of patients (13%
      for RF, 1% for ACPA and 9% for RF/ACPA) might or might not be classified as RA
      according to the 2010 ACR/EULAR criteria. CONCLUSION: Due to poor harmonisation
      of RF and ACPA assays and of test result interpretation, RA classification
      according to 2010 ACR/EULAR criteria may vary when different assays are used.

PMID- 29363511
TI  - Efficacy of infliximab in the treatment of Erdheim-Chester disease.

PMID- 29363512
TI  - Response to letter: 'Response to: 'Neuropsychiatric lupus or not? Cerebral
      hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in
      primary neuropsychiatric lupus erythematosus' by Papadaki et al' by Wallace.

PMID- 29363514
TI  - Physician associates: different from but complementary to general practitioners.

PMID- 29363513
TI  - Anti-NT5C1A autoantibodies are associated with more severe disease in patients
      with juvenile myositis.
AB  - OBJECTIVES: Autoantibodies recognising cytosolic 5'-nucleotidase 1A (NT5C1A) are
      found in adult patients with myositis and other autoimmune diseases. They are
      especially prevalent in adults with inclusion body myositis (IBM), in which they
      are associated with more severe weakness and higher mortality. This study was
      undertaken to define the prevalence and clinical features associated with anti
      NT5C1A autoantibodies in juvenile myositis. METHODS: We screened sera from 380
      patients with juvenile myositis, 30 patients with juvenile idiopathic arthritis
      (JIA) and 92 healthy control children for anti-NT5C1A autoantibodies. Clinical
      characteristics were compared between patients with myositis with and without
      anti-NT5C1A autoantibodies. RESULTS: Anti-NT5C1A autoantibodies were present in
      102 of 380 (27%) patients with juvenile myositis and in 11 of 92 (12%) healthy
      control children (P=0.002) and 27% of children with JIA (P=0.05 vs controls).
      Sera of 83 of 307 (27%) patients with juvenile dermatomyositis and 16 of 46 (35%)
      patients with juvenile overlap myositis were anti-NT5C1A autoantibody-positive
      (P<0.01 vs healthy controls for each), but sera of only 3 of 27 (11%) patients
      with juvenile polymyositis were anti-NT5C1A-positive. Patients with juvenile
      myositis with and without anti-NT5C1A autoantibodies had similar clinical
      phenotypes. However, patients with anti-NT5C1A autoantibody-positive myositis had
      greater pulmonary symptoms at diagnosis (P=0.005), more frequent hospitalisations
      (P=0.01) and required a larger number of medications (P<0.001). CONCLUSION: Anti
      NT5C1A autoantibodies are present in more than one-quarter of children with
      juvenile myositis and JIA compared with only 12% of healthy children, suggesting
      they are myositis-associated in children. As in adults with IBM, patients with
      juvenile myositis with anti-NT5C1A autoantibodies have more severe disease.

PMID- 29363516
TI  - The Evolving Role of Intranasal Dexmedetomidine for Pediatric Procedural
      Sedation.

PMID- 29363517
TI  - Use of Intranasal Dexmedetomidine as a Solo Sedative for MRI of Infants.
AB  - BACKGROUND: Dexmedetomidine, a selective alpha-2 receptor agonist, can be
      delivered via the intranasal (IN) route and be used for procedural sedation. The
      drug's favorable hemodynamic profile and relative ease of application make it a
      promising agent for sedation during radiologic procedures, although there are few
      studies on its efficacy for MRI studies. METHODS: A retrospective chart review
      was performed between June 2014 and December 2016. Outpatients between 1 and 12
      months of age who received 4 MUg/kg of IN dexmedetomidine for MRI were included
      in the analysis. Our aim with this study was to determine the rate of successful
      completion of the sedation procedure without the need for a rescue drug (other
      than repeat IN dexmedetomidine). RESULTS: A total of 52 subjects were included in
      our study. Median (interquartile range) patient age was 7 (5-8) months. Median
      (interquartile range) procedure length was 40 (35-50) minutes. Overall success
      rate (including first dose and any rescue dose IN) of dexmedetomidine was 96.2%.
      None of the patients had significant adverse effects related to dexmedetomidine.
      CONCLUSIONS: IN dexmedetomidine is an effective solo sedative agent for MRI in
      infants.

PMID- 29363515
TI  - Genome-Wide Screen for New Components of the Drosophila melanogaster Torso
      Receptor Tyrosine Kinase Pathway.
AB  - Patterning of the Drosophila embryonic termini by the Torso (Tor) receptor
      pathway has long served as a valuable paradigm for understanding how receptor
      tyrosine kinase signaling is controlled. However, the mechanisms that underpin
      the control of Tor signaling remain to be fully understood. In particular, it is
      unclear how the Perforin-like protein Torso-like (Tsl) localizes Tor activity to
      the embryonic termini. To shed light on this, together with other aspects of Tor
      pathway function, we conducted a genome-wide screen to identify new pathway
      components that operate downstream of Tsl. Using a set of molecularly defined
      chromosomal deficiencies, we screened for suppressors of ligand-dependent Tor
      signaling induced by unrestricted Tsl expression. This approach yielded 59
      genomic suppressor regions, 11 of which we mapped to the causative gene, and a
      further 29 that were mapped to <15 genes. Of the identified genes, six represent
      previously unknown regulators of embryonic Tor signaling. These include twins
      (tws), which encodes an integral subunit of the protein phosphatase 2A complex,
      and alpha-tubulin at 84B (alphaTub84B), a major constituent of the microtubule
      network, suggesting that these may play an important part in terminal patterning.
      Together, these data comprise a valuable resource for the discovery of new Tor
      pathway components. Many of these may also be required for other roles of Tor in
      development, such as in the larval prothoracic gland where Tor signaling controls
      the initiation of metamorphosis.

PMID- 29363518
TI  - Serum biomarkers in periprosthetic joint infections.
AB  - OBJECTIVES: The diagnosis of periprosthetic joint infection (PJI) is difficult
      and requires a battery of tests and clinical findings. The purpose of this review
      is to summarize all current evidence for common and new serum biomarkers utilized
      in the diagnosis of PJI. METHODS: We searched two literature databases, using
      terms that encompass all hip and knee arthroplasty procedures, as well as PJI and
      statistical terms reflecting diagnostic parameters. The findings are summarized
      as a narrative review. RESULTS: Erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) were the two most commonly published serum biomarkers.
      Most evidence did not identify other serum biomarkers that are clearly superior
      to ESR and CRP. Other serum biomarkers have not demonstrated superior sensitivity
      and have failed to replace CRP and ESR as first-line screening tests. D-dimer
      appears to be a promising biomarker, but more research is necessary. Factors that
      influence serum biomarkers include temporal trends, stage of revision, and
      implant-related factors (metallosis). CONCLUSION: Our review helped to identify
      factors that can influence serum biomarkers' level changes; the recognition of
      such factors can help improve their diagnostic utility. As such, we cannot rely
      on ESR and CRP alone for the diagnosis of PJI prior to second-stage
      reimplantation, or in metal-on-metal or corrosion cases. The future of serum
      biomarkers will likely shift towards using genomics and proteomics to identify
      proteins transcribed via messenger RNA in response to infection and sepsis.Cite
      this article:Bone Joint Res 2018;7:85-93.

PMID- 29363519
TI  - Increased sclerostin associated with stress fracture of the third metacarpal bone
      in the Thoroughbred racehorse.
AB  - OBJECTIVES: The exact aetiology and pathogenesis of microdamage-induced long bone
      fractures remain unknown. These fractures are likely to be the result of
      inadequate bone remodelling in response to damage. This study aims to identify an
      association of osteocyte apoptosis, the presence of osteocytic osteolysis, and
      any alterations in sclerostin expression with a fracture of the third metacarpal
      (Mc-III) bone of Thoroughbred racehorses. METHODS: A total of 30 Mc-III bones
      were obtained; ten bones were fractured during racing, ten were from the
      contralateral limb, and ten were from control horses. Each Mc-III bone was
      divided into a fracture site, condyle, condylar groove, and sagittal ridge.
      Microcracks and diffuse microdamage were quantified. Apoptotic osteocytes were
      measured using TUNEL staining. Cathepsin K, matrix metalloproteinase-13 (MMP-13),
      HtrA1, and sclerostin expression were analyzed. RESULTS: In the fracture group,
      microdamage was elevated 38.9% (sd 2.6) compared with controls. There was no
      difference in the osteocyte number and the percentage of apoptotic cells between
      contralateral limb and unraced control; however, there were significantly fewer
      apoptotic cells in fractured samples (p < 0.02). Immunohistochemistry showed that
      in deep zones of the fractured samples, sclerostin expression was significantly
      higher (p < 0.03) than the total number of osteocytes. No increase in cathepsin
      K, MMP-13, or HtrA1 was present. CONCLUSION: There is increased microdamage in Mc
      III bones that have fractured during racing. In this study, this is not
      associated with osteocyte apoptosis or osteocytic osteolysis. The finding of
      increased sclerostin in the region of the fracture suggests that this protein may
      be playing a key role in the regulation of bone microdamage during stress
      adaptation.Cite this article:Bone Joint Res 2018;7:94-102.

PMID- 29363520
TI  - Intraoperative femoral fractures: Prevention is better than cure.

PMID- 29363521
TI  - The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical
      bone.
AB  - OBJECTIVES: Advanced glycation end-products (AGEs) are a post-translational
      modification of collagen that form spontaneously in the skeletal matrix due to
      the presence of reducing sugars, such as glucose. The accumulation of AGEs leads
      to collagen cross-linking, which adversely affects bone quality and has been
      shown to play a major role in fracture risk. Thus, intervening in the formation
      and accumulation of AGEs may be a viable means of protecting bone quality.
      METHODS: An in vitro model was used to examine the efficacy of two AGE
      inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical
      bone. Mid-diaphyseal tibial cortical bone segments were obtained from female
      cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one
      of four treatments: control; glucose only; glucose and AG; or glucose and PM.
      Following treatment, each specimen underwent mechanical testing under
      physiological conditions via reference point indentation, and AGEs were
      quantified by fluorescence. RESULTS: Treatment with AG and PM showed a
      significant decrease in AGE content versus control groups, as well as a
      significant decrease in the change in indentation distance, a reliable parameter
      for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05).
      CONCLUSIONS: The data suggest that AG and PM prevent AGE formation and subsequent
      biomechanical degradation in vitro. Modulation of AGEs may help to identify novel
      therapeutic targets to mitigate bone quality deterioration, especially
      deterioration due to ageing and in AGE-susceptible populations (e.g.
      diabetics).Cite this article: Bone Joint Res 2018;7:105-110.

PMID- 29363524
TI  - Acquired Resistance of ER-Positive Breast Cancer to Endocrine Treatment Confers
      an Adaptive Sensitivity to TRAIL through Posttranslational Downregulation of c
      FLIP.
AB  - Purpose: One third of ER-positive breast cancer patients who initially respond to
      endocrine therapy become resistant to treatment. Such treatment failure is
      associated with poor prognosis and remains an area of unmet clinical need. Here,
      we identify a specific posttranslational modification that occurs during
      endocrine resistance and which results in tumor susceptibility to the apoptosis
      inducer TRAIL. This potentially offers a novel stratified approach to targeting
      endocrine-resistant breast cancer.Experimental Design: Cell line and primary
      derived xenograft models of endocrine resistance were investigated for
      susceptibility to TRAIL. Tumor viability, cancer stem cell (CSC) viability
      (tumorspheres), tumor growth kinetics, and metastatic burden were assessed.
      Western blots for the TRAIL-pathway inhibitor, c-FLIP, and upstream regulators
      were performed. Results were confirmed in primary culture of 26 endocrine
      resistant and endocrine-naive breast tumors.Results: Breast cancer cell lines
      with acquired resistance to tamoxifen (TAMR) or faslodex were more sensitive to
      TRAIL than their endocrine-sensitive controls. Moreover, TRAIL eliminated CSC
      like activity in TAMR cells, resulting in prolonged remission of xenografts in
      vivo In primary culture, TRAIL significantly depleted CSCs in 85% endocrine
      resistant, compared with 8% endocrine-naive, tumors, whereas systemic
      administration of TRAIL in endocrine-resistant patient-derived xenografts reduced
      tumor growth, CSC-like activity, and metastases. Acquired TRAIL sensitivity
      correlated with a reduction in intracellular levels of c-FLIP, and an increase in
      Jnk-mediated phosphorylation of E3-ligase, ITCH, which degrades c
      FLIP.Conclusions: These results identify a novel mechanism of acquired
      vulnerability to an extrinsic cell death stimulus, in endocrine-resistant breast
      cancers, which has both therapeutic and prognostic potential. Clin Cancer Res;
      24(10); 2452-63. (c)2018 AACR.

PMID- 29363522
TI  - Experimental and numerical investigation into the influence of loading conditions
      in biomechanical testing of locking plate fracture fixation devices.
AB  - OBJECTIVES: Secondary fracture healing is strongly influenced by the stiffness of
      the bone-fixator system. Biomechanical tests are extensively used to investigate
      stiffness and strength of fixation devices. The stiffness values reported in the
      literature for locked plating, however, vary by three orders of magnitude. The
      aim of this study was to examine the influence that the method of restraint and
      load application has on the stiffness produced, the strain distribution within
      the bone, and the stresses in the implant for locking plate constructs. METHODS:
      Synthetic composite bones were used to evaluate experimentally the influence of
      four different methods of loading and restraining specimens, all used in recent
      previous studies. Two plate types and three screw arrangements were also
      evaluated for each loading scenario. Computational models were also developed and
      validated using the experimental tests. RESULTS: The method of loading was found
      to affect the gap stiffness strongly (by up to six times) but also the magnitude
      of the plate stress and the location and magnitude of strains at the bone-screw
      interface. CONCLUSIONS: This study demonstrates that the method of loading is
      responsible for much of the difference in reported stiffness values in the
      literature. It also shows that previous contradictory findings, such as the
      influence of working length and very large differences in failure loads, can be
      readily explained by the choice of loading condition.Cite this article:Bone Joint
      Res 2018;7:111-120.

PMID- 29363525
TI  - Hybrid Capture-Based Genomic Profiling of Circulating Tumor DNA from Patients
      with Advanced Cancers of the Gastrointestinal Tract or Anus.
AB  - Purpose: Genomic profiling of tumor biopsies from advanced gastrointestinal and
      anal cancers is increasingly used to inform treatment. In some cases, tissue
      biopsy can be prohibitive, and we sought to investigate whether analysis of blood
      derived circulating tumor DNA (ctDNA) may provide a minimally invasive
      alternative.Experimental Design: Hybrid capture-based genomic profiling of 62
      genes was performed on blood-based ctDNA from 417 patients with gastrointestinal
      carcinomas to assess the presence of genomic alterations (GA) and compare with
      matched tissue samples.Results: Evidence of ctDNA was detected in 344 of 417
      samples (82%), and of these, >=1 reportable GA was detected in 89% (306/344) of
      samples. Frequently altered genes were TP53 (72%), KRAS (35%), PIK3CA (14%), BRAF
      (8%), and EGFR (7%). In temporally matched ctDNA and tissue samples available
      from 25 patients, 86% of alterations detected in tissue were also detected in
      ctDNA, including 95% of short variants, but only 50% of amplifications.
      Conversely, 63% of alterations detected in ctDNA were also detected in matched
      tissue. Examples demonstrating clinical utility are presented.Conclusions:
      Genomic profiling of ctDNA detected potentially clinically relevant GAs in a
      significant subset of patients with gastrointestinal carcinomas. In these tumor
      types, most alterations detected in matched tissue were also detected in ctDNA,
      and with the exception of amplifications, ctDNA sequencing routinely detected
      additional alterations not found in matched tissue, consistent with tumor
      heterogeneity. These results suggest feasibility and utility of ctDNA testing in
      advanced gastrointestinal cancers as a complementary approach to tissue testing,
      and further investigation is warranted. Clin Cancer Res; 24(8); 1881-90. (c)2018
      AACR.

PMID- 29363526
TI  - Nitric Oxide Production by Myeloid-Derived Suppressor Cells Plays a Role in
      Impairing Fc Receptor-Mediated Natural Killer Cell Function.
AB  - Purpose: mAbs are used to treat solid and hematologic malignancies and work in
      part through Fc receptors (FcRs) on natural killer cells (NK). However, FcR
      mediated functions of NK cells from patients with cancer are significantly
      impaired. Identifying the mechanisms of this dysfunction and impaired response to
      mAb therapy could lead to combination therapies and enhance mAb
      therapy.Experimental Design: Cocultures of autologous NK cells and MDSC from
      patients with cancer were used to study the effect of myeloid-derived suppressor
      cells (MDSCs) on NK-cell FcR-mediated functions including antibody-dependent
      cellular cytotoxicity, cytokine production, and signal transduction in vitro
      Mouse breast cancer models were utilized to study the effect of MDSCs on antibody
      therapy in vivo and test the efficacy of combination therapies including a mAb
      and an MDSC-targeting agent.Results: MDSCs from patients with cancer were found
      to significantly inhibit NK-cell FcR-mediated functions including antibody
      dependent cellular cytotoxicity, cytokine production, and signal transduction in
      a contact-independent manner. In addition, adoptive transfer of MDSCs abolished
      the efficacy of mAb therapy in a mouse model of pancreatic cancer. Inhibition of
      iNOS restored NK-cell functions and signal transduction. Finally, nonspecific
      elimination of MDSCs or inhibition of iNOS in vivo significantly improved the
      efficacy of mAb therapy in a mouse model of breast cancer.Conclusions: MDSCs
      antagonize NK-cell FcR-mediated function and signal transduction leading to
      impaired response to mAb therapy in part through nitric oxide production. Thus,
      elimination of MDSCs or inhibition of nitric oxide production offers a strategy
      to improve mAb therapy. Clin Cancer Res; 24(8); 1891-904. (c)2018 AACR.

PMID- 29363528
TI  - Doctor who failed to curb his abusive behaviour is struck off.

PMID- 29363527
TI  - The impact of environmental temperature on the diagnosis of gestational diabetes
      mellitus.
AB  - OBJECTIVE: To investigate a probable impact of seasons on the diagnosis of GDM,
      as well as the specific effect of the environmental temperature on the diagnosis
      of this clinical entity. PATIENTS AND METHODS: Two observational studies, one
      retrospective and one prospective, were conducted in a referral center. Study A
      included retrospectively 7618 pregnant women who underwent a 3-h 100 g OGTT
      during the 3rd trimester of gestation. Study B prospectively included 768
      pregnant women tested in the 3rd trimester of gestation with a 75 g OGTT.
      Temperature was recorded every day at 09:00 h. RESULTS: Retrospective Study A:
      GDM prevalence differed significantly by season: winter = 28.1%, summer = 39.2%,
      spring = 32.4% and autumn = 32.4% (P < 0.0001). The odds ratio for being
      diagnosed with GDM was much higher during summer 1.65 (95% CI: 1.43-1.90), with
      spring and autumn following with 1.23 (95% CI: 1.08-1.39) compared to winter.
      Glucose levels during OGTT were measured: significantly increased blood glucose
      values were observed at 60, 120 and 180 min in summer, which remained significant
      after adjustment for age, gestational age, BMI, weight gain during pregnancy and
      blood pressure. Prospective Study B: At temperatures above 25 degrees C, the
      average glucose 60-min and 120-min levels were increased. The relative risk for
      abnormal glucose values at 60 min, when the environmental temperature increased
      over 25 degrees C, was 2.2 (1.5-3.3). CONCLUSIONS: GDM prevalence in Greece
      presents seasonal variation, with higher risk during summer due to post glucose
      load level variations. These variations could be attributed to differences in
      environmental temperature.

PMID- 29363529
TI  - Clinical features of demyelinating optic neuritis with seropositive myelin
      oligodendrocyte glycoprotein antibody in Chinese patients.
AB  - BACKGROUND/AIMS: To investigate the clinical features of Chinese patients with
      seropositive myelin oligodendrocyte glycoprotein antibody (MOG-Ab) optic neuritis
      (ON) and patients with seropositive aquaporin-4 antibody (AQP4-Ab) ON. METHODS:
      In this retrospective observational study, sera from patients with demyelinating
      ON were tested for MOG-Ab and AQP4-Ab with a cell-based assay. Clinical
      characteristics were compared between MOG-Ab-related ON (MOG-ON) and AQP4-Ab
      related ON (AQP4-ON), including visual performances, serum autoantibodies and
      features on MRI. RESULTS: A total of 109 affected eyes from 65 patients with
      demyelinating ON (20 MOG-ON and 45 AQP4-ON) were included. The onset age of MOG
      ON was younger than AQP4-ON (MOG-ON: 20.2+/-17.4 years old, AQP4-ON: 35.6+/-15.7
      years old, P=0.001). Onset severity was not different between these two groups
      (P=0.112), but patients with MOG-ON showed better visual outcomes (P=0.004). Half
      of the MOG-ON had a relapsing disease course. Nineteen per cent of patients with
      AQP4-ON presented coexisting autoimmune disorders, but there were no coexisting
      autoimmune disorders among patients with MOG-ON. Optic nerve head swelling was
      more prevalent in patients with MOG-ON (P<0.01). Retrobulbar segment involvement
      of the optic nerve were more common in patients with MOG-ON according to our MRI
      findings (P<0.01). Patients with MOG-ON showed longitudinally extensive lesion in
      30% and chiasm and optic tract involvement in 5%. CONCLUSIONS: MOG-ON is not rare
      in Chinese demyelinating patients. It underwent a severe vision loss at onset but
      had relatively better visual recovery than patients with AQP4-ON. MOG-ON might
      have an unique pathogenesis different from AQP4-ON.

PMID- 29363530
TI  - Topical ganciclovir treatment post-Descemet's stripping automated endothelial
      keratoplasty for patients with bullous keratopathy induced by cytomegalovirus.
AB  - BACKGROUND/AIMS: To investigate the efficacy of topical ganciclovir (GCV) for
      preventing disease recurrence and improving the surgical outcome post-Descemet's
      stripping automated endothelial keratoplasty (DSAEK) in patients with
      cytomegalovirus (CMV) endotheliitis. METHODS: This prospective, non-comparative
      case series study involved six eyes of six patients with endothelial
      decompensation due to CMV endotheliitis who underwent DSAEK, followed by a
      continuous, four to six times daily, topical administration of 0.5% GCV. Patient
      demographics, clinical history, and preoperative and postoperative examination
      (including any recurrence of CMV endotheliitis post-DSAEK), best corrected visual
      acuity (BCVA), intraocular pressure (IOP), graft survival rate and endothelial
      cell density (ECD) were examined. RESULTS: No recurrence of CMV endotheliitis was
      detected post-DSAEK. The mean follow-up period was 40 months (range, 12-60
      months). The mean preoperative BCVA was 1.52+/-0.68 LogMAR (range, 0.52-2.40
      LogMAR), yet it had significantly improved to 0.15+/-0.16 LogMAR (range: -0.08 to
      0.30 LogMAR) by 1 year postoperative (P<0.01). In all patients, IOP was well
      controlled (10-20 mm Hg) postsurgery. The mean preoperative donor ECD was 2692+/
      177 cells/mm2, and the mean postoperative ECD was 1974, 1771 and 1174 cells/mm2
      for the ECD loss of 26%, 33% and 54% at 6, 12 and 36 months, respectively. No
      adverse effects were observed associated with the long-term topical
      administration of GCV. CONCLUSION: The continuous topical application of 0.5% GCV
      was found to be effective for preventing the recurrence of CMV endotheliitis, and
      it provided the optimal mid-term clinical outcomes post-DSAEK in patients with
      CMV endotheliitis. TRIAL REGISTRATION NUMBER: UMIN000026746.

PMID- 29363531
TI  - Retinal vascular alterations in reticular pseudodrusen with and without outer
      retinal atrophy assessed by optical coherence tomography angiography.
AB  - PURPOSE: To investigate the intraretinal structural and vascular alterations in
      patients featuring reticular pseudodrusen (RPD), RPD with outer retinal atrophy
      (ORA), and drusen. DESIGN: Observational cross-sectional study. METHODS: Clinical
      practice study including 68 eyes of 57 patients (22 eyes of 17 patients with RPD;
      24 eyes of 21 patients with RPD+ORA; 22 eyes of 19 patients with drusen). Each
      patient underwent spectral-domain optical coherence tomography (OCT) and OCT
      angiography (OCT-A). Measurement of retinal layers' thickness was obtained by the
      automated segmentation protocol of the Spectralis OCT (Heidelberg Eye Explorer
      V.1.9.10.0). The superficial capillary plexus (SCP) and the deep capillary plexus
      (DCP) vessel density, as well as the size of the foveal avascular zone were
      calculated on 3*3 OCT-A. Main outcome was to compare vessel density at the SCP
      and DCP among the groups and controls. RESULTS: At the SCP, the vessel density
      was lower in RPD and RPD+ORA patients with respect to controls (P=0.02 and
      P=0.003, respectively). At the DCP, meaningful disparity was found between the
      study groups and the healthy subjects in the vessel density (P<0.001, P=0.04 and
      P=0.001 for RPD, RDP+ORA and drusen, respectively). The ganglion cell layer (GCL)
      was thinner in all patients affected either by RPD, RPD+ORA or drusen compared
      with healthy subjects (P=0.02, P=0.03 and P=0.004, respectively). CONCLUSION:
      Significant retinal vascular loss is a common feature of patients with non
      exudative age-related macular degeneration, more pronounced in those featuring
      RPD and RPD+ORA. It is associated with retinal thinning, localised particularly
      at the GCL, compared with controls.

PMID- 29363532
TI  - Automated diabetic retinopathy detection using optical coherence tomography
      angiography: a pilot study.
AB  - BACKGROUND: Optical coherence tomography angiography (OCTA) is increasingly being
      used to evaluate diabetic retinopathy, but the interpretation of OCTA remains
      largely subjective. The purpose of this study was to design a computer-aided
      diagnostic (CAD) system to diagnose non-proliferative diabetic retinopathy (NPDR)
      in an automated fashion using OCTA images. METHODS: This was a two-centre, cross
      sectional study. Adults with type II diabetes mellitus (DMII) were eligible for
      inclusion. OCTA scans of the macula were taken, and the five vascular maps
      generated per eye were analysed by a novel CAD system. For the purpose of
      classification/diagnosis, three different local features-blood vessel density,
      blood vessel calibre and the size of the foveal avascular zone (FAZ)-were
      segmented from these images and used to train a new, automated classifier.
      RESULTS: One hundred and six patients with DMII were included in the study, 23
      with no DR and 83 with mild NPDR. When using features of the superficial retinal
      map alone, the system demonstrated an accuracy of 80.0% and area under the curve
      (AUC) of 76.2%. Using the features of the deep retinal map alone, accuracy was
      91.4% and AUC 89.2%. When data from both maps were combined, the presented CAD
      system demonstrated overall accuracy of 94.3%, sensitivity of 97.9%, specificity
      of 87.0%, area under curve (AUC) of 92.4% and dice similarity coefficient of
      95.8%. CONCLUSION: Automated diagnosis of NPDR using OCTA images is feasible and
      accurate. Combining this system with OCT data is a plausible next step that would
      likely improve its robustness.

PMID- 29363533
TI  - Report on the incidence of squamous cell carcinomas affecting the eyelids in
      England over a 15-year period (2000-2014).
AB  - AIMS: The authors report on trends in the incidence of squamous cell carcinoma
      (SCC) affecting the eyelids in England over a 15-year period and identify
      associations between demographic factors and SCC risk. METHODS: The National
      Cancer Registration and Analysis Service identified all cases of eyelid SCC in
      England between 2000 and 2014. The crude and age-standardised rates of eyelid
      SCCs in England were calculated. The association of SCC with several known
      demographic risk factors was then examined to assess their importance in
      periocular cases. RESULTS: Over the 15 years studied, there were 4022 patients in
      England diagnosed with a first episode of SCC affecting the eyelids. The age
      standardised number of reported cases rose between 2000 and 2014 by a mean of
      0.0137 cases per 100 000 population per year (equivalent to a rise in SCC
      incidence of approximately 2% per year). The mean age-standardised incidence rate
      of SCC during the study period was 0.63 cases per 100 000 population per year.Age
      was exponentially correlated with incidence, with an approximate doubling of the
      risk for every decade over the age of 60. The relative risk of eyelid SCC in men
      compared with women was 1.9. Social deprivation quintile by income was not found
      to be associated with risk of SCC. CONCLUSION: The incidence of eyelid SCC in
      England is rising. In addition, the age-standardised and population-standardised
      rate of SCC is also rising. A higher risk of SCC is strongly correlated with age
      and male sex but not with deprivation.

PMID- 29363535
TI  - Improved adenoma detection with Endocuff Vision: the ADENOMA randomised
      controlled trial.
AB  - OBJECTIVE: Low adenoma detection rates (ADR) are linked to increased
      postcolonoscopy colorectal cancer rates and reduced cancer survival. Devices to
      enhance mucosal visualisation such as Endocuff Vision (EV) may improve ADR. This
      multicentre randomised controlled trial compared ADR between EV-assisted
      colonoscopy (EAC) and standard colonoscopy (SC). DESIGN: Patients referred
      because of symptoms, surveillance or following a positive faecal occult blood
      test (FOBt) as part of the Bowel Cancer Screening Programme were recruited from
      seven hospitals. ADR, mean adenomas per procedure, size and location of adenomas,
      sessile serrated polyps, EV removal rate, caecal intubation rate, procedural
      time, patient experience, effect of EV on workload and adverse events were
      measured. RESULTS: 1772 patients (57% male, mean age 62 years) were recruited
      over 16 months with 45% recruited through screening. EAC increased ADR globally
      from 36.2% to 40.9% (P=0.02). The increase was driven by a 10.8% increase in FOBt
      positive screening patients (50.9% SC vs 61.7% EAC, P<0.001). EV patients had
      higher detection of mean adenomas per procedure, sessile serrated polyps, left
      sided, diminutive, small adenomas and cancers (cancer 4.1% vs 2.3%, P=0.02). EV
      removal rate was 4.1%. Median intubation was a minute quicker with EAC (P=0.001),
      with no difference in caecal intubation rate or withdrawal time. EAC was well
      tolerated but caused a minor increase in discomfort on anal intubation in
      patients undergoing colonoscopy with no or minimal sedation. There were no
      significant EV adverse events. CONCLUSION: EV significantly improved ADR in bowel
      cancer screening patients and should be used to improve colonoscopic detection.
      TRIAL REGISTRATION NUMBER: NCT 02552017, Results; ISRCTN 11821044, Results.

PMID- 29363536
TI  - Cell of origin affects tumour development and phenotype in pancreatic ductal
      adenocarcinoma.
AB  - OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumour
      thought to arise from ductal cells via pancreatic intraepithelial neoplasia
      (PanIN) precursor lesions. Modelling of different genetic events in mice suggests
      both ductal and acinar cells can give rise to PDAC. However, the impact of
      cellular context alone on tumour development and phenotype is unknown. DESIGN: We
      examined the contribution of cellular origin to PDAC development by inducing PDAC
      associated mutations, KrasG12D expression and Trp53 loss, specifically in ductal
      cells (Sox9CreER;KrasLSL-G12D;Trp53flox/flox ('Duct:KPcKO ')) or acinar cells
      (Ptf1aCreER;KrasLSL-G12D;Trp53flox/flox ('Acinar:KPcKO ')) in mice. We then
      performed a thorough analysis of the resulting histopathological changes.
      RESULTS: Both mouse models developed PDAC, but Duct:KPcKO mice developed PDAC
      earlier than Acinar:KPcKO mice. Tumour development was more rapid and associated
      with high-grade murine PanIN (mPanIN) lesions in Duct:KPcKO mice. In contrast,
      Acinar:KPcKO mice exhibited widespread metaplasia and low-grade as well as high
      grade mPanINs with delayed progression to PDAC. Acinar-cell-derived tumours also
      had a higher prevalence of mucinous glandular features reminiscent of early
      mPanIN lesions. CONCLUSION: These findings indicate that ductal cells are primed
      to form carcinoma in situ that become invasive PDAC in the presence of oncogenic
      Kras and Trp53 deletion, while acinar cells with the same mutations appear to
      require a prolonged period of transition or reprogramming to initiate PDAC. Our
      findings illustrate that PDAC can develop in multiple ways and the cellular
      context in which mutations are acquired has significant impact on precursor
      lesion initiation, disease progression and tumour phenotype.

PMID- 29363537
TI  - Magnitude and Pattern of Placebo Response in Clinical Trials of Oral
      Antihyperglycemic Agents: Data From the U.S. Food and Drug Administration, 1999
      2015.
AB  - OBJECTIVE: To evaluate the magnitude of placebo response and treatment response
      patterns in clinical trials of investigational oral antihyperglycemics over time.
      RESEARCH DESIGN AND METHODS: We examined the U.S. Food and Drug Administration
      medical and statistical reviews for 19 oral antihyperglycemic agents (23,438
      patients, 50 trials, and 96 treatment arms) approved between 1999 and 2015.
      Placebo and medication treatment response (HbA1c reduction) and effect sizes were
      examined over time (year of approval). Exclusively placebo-controlled and
      augmented/adjunctive placebo-controlled trials were analyzed separately, and
      differences were compared. Potential effects of trial and patient characteristics
      were explored. RESULTS: In more recent trials, augmented placebo-controlled arms
      reduced HbA1c by 0.2% on average and more frequently lowered HbA1c from baseline
      compared with exclusively placebo-controlled arms (63 vs. 18%; chi2 = 9.93; P =
      0.002). In exclusively placebo-controlled trials, placebo response increased
      significantly over time (beta = 0.035; R2 = 0.31; P = 0.0013), reaching ~0%
      average change in HbA1c, whereas drug response also increased significantly (beta
      = 0.017; R2 = 0.076; P = 0.0498). In augmented placebo-controlled trials, placebo
      response (beta = 0.33; R2 = 0.407; P < 0.001) showed the same pattern, whereas
      the growth in drug response was not significant (R2 = 0.031; P = 0.207). Placebo
      response in both groups increased by 0.5% HbA1c reduction over time, whereas
      effect sizes remained stable with high success rates (100%; 96 out of 96). Drug
      response and effect size were not significantly predicted by patient or trial
      characteristics, but follow-up analysis suggested an inverse relationship of
      placebo baseline HbA1c with placebo response. CONCLUSIONS: Remarkably, placebo
      treated patients with diabetes commonly experienced reduction in HbA1c, more
      markedly in augmented compared with exclusively placebo-controlled treatment
      arms. Placebo response increased significantly over time without impacting
      efficacy outcomes. Nonpharmacologic effects measured in the placebo response
      appear stronger when used with active medication than when implemented in
      isolation and may be related to the level of HbA1c at baseline.

PMID- 29363534
TI  - Natural disease course of Crohn's disease during the first 5 years after
      diagnosis in a European population-based inception cohort: an Epi-IBD study.
AB  - OBJECTIVE: The Epi-IBD cohort is a prospective population-based inception cohort
      of unselected patients with inflammatory bowel disease from 29 European centres
      covering a background population of almost 10 million people. The aim of this
      study was to assess the 5-year outcome and disease course of patients with
      Crohn's disease (CD). DESIGN: Patients were followed up prospectively from the
      time of diagnosis, including collection of their clinical data, demographics,
      disease activity, medical therapy, surgery, cancers and deaths. Associations
      between outcomes and multiple covariates were analysed by Cox regression
      analysis. RESULTS: In total, 488 patients were included in the study. During
      follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were
      hospitalised because of CD. A total of 49 (14%) patients diagnosed with non
      stricturing, non-penetrating disease progressed to either stricturing and/or
      penetrating disease. These rates did not differ between patients from Western and
      Eastern Europe. However, significant geographic differences were noted regarding
      treatment: more patients in Western Europe received biological therapy (33%) and
      immunomodulators (66%) than did those in Eastern Europe (14% and 54%,
      respectively, P<0.01), while more Eastern European patients received 5
      aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced
      the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3,
      95% CI 0.2 to 0.5). CONCLUSION: Despite patients being treated early and
      frequently with immunomodulators and biological therapy in Western Europe, 5-year
      outcomes including surgery and phenotype progression in this cohort were
      comparable across Western and Eastern Europe. Differences in treatment strategies
      between Western and Eastern European centres did not affect the disease course.
      Treatment with immunomodulators reduced the risk of surgery and hospitalisation.

PMID- 29363538
TI  - Implementation of a Structured Diabetes Consultation Model to Facilitate a Person
      Centered Approach: Results From a Nationwide Dutch Study.
AB  - OBJECTIVE: We assessed both from a patient and provider perspective the
      usefulness and added value of a consultation model that facilitates person
      centered diabetes care. RESEARCH DESIGN AND METHODS: The model consists of 1)
      inventory of disease and patient-related factors; 2) setting personal goals; 3)
      choosing treatment; and 4) determination of required care. It was implemented in
      47 general practices and 6 hospital outpatient clinics. Providers were trained,
      and patients were recommended to prepare their visit. All filled out a
      questionnaire after every consultation. Differences between primary and secondary
      care practices and between physician-led and nurse-led consultations were
      analyzed. RESULTS: Seventy-four physicians and thirty-one nurses participated,
      reporting on 1,366 consultations with type 2 diabetes patients. According to
      providers, the model was applicable in 72.4% (nurses 79.3% vs. physicians 68.5%,
      P < 0.001). Physicians more often had a consultation time <25 min (80.4% vs.
      56.9%, P < 0.001). According to providers, two of three patients spoke more than
      half of the consultation time (outpatient clinics 75.2% vs. general practices
      66.6%, P = 0.002; nurses 73.2% vs. physicians 64.4%, P = 0.001). Providers stated
      that person-related factors often determined treatment goals. Almost all patients
      (94.4%) reported that they made shared decisions; they felt more involved than
      before (with physicians 45.1% vs. with nurses 33.6%, P < 0.001) and rated the
      consultation 8.6 of 10. After physician-led consultations, 52.5% reported that
      the consultation was better than before (nurse visit 33.7%, P < 0.001).
      CONCLUSIONS: A consultation model to facilitate person-centered care seems well
      applicable and results in more patient involvement, including shared decision
      making, and is appreciated by a substantial number of patients.

PMID- 29363539
TI  - Nucleic acid based therapies: developing frontier for precision medicine.

PMID- 29363541
TI  - Vitamin A-coupled liposomes containing siRNA against HSP47 ameliorate skin
      fibrosis in chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell
      transplantation (SCT) is characterized by multiorgan fibrosis and profoundly
      affects the quality of life of transplant survivors. Heat shock protein 47
      (HSP47), a collagen-specific molecular chaperone, plays a critical role in
      collagen synthesis in myofibroblasts. We explored the role of HSP47 in the
      fibrotic process of cutaneous chronic GVHD in mice. Immunohistochemical analysis
      showed massive fibrosis with elevated amounts of collagen deposits and
      accumulation of F4/80+ macrophages, as well as myofibroblasts expressing HSP47
      and retinol-binding protein 1 in the skin after allogeneic SCT. Repeated
      injection of anti-colony-stimulating factor (CSF-1) receptor-blocking antibodies
      significantly reduced HSP47+ myofibroblasts in the skin, indicating a macrophage
      dependent accumulation of myofibroblasts. Vitamin A-coupled liposomes carrying
      HSP47 small interfering RNA (siRNA) (VA-lip HSP47) delivered HSP47 siRNA to cells
      expressing vitamin A receptors and knocked down their HSP47 in vitro.
      Intravenously injected VA-lip HSP47 were specifically distributed to skin
      fibrotic lesions and did not affect collagen synthesis in healthy skin. VA-lip
      HSP47 knocked down HSP47 expression in myofibroblasts and significantly reduced
      collagen deposition without inducing systemic immunosuppression. It also
      abrogated fibrosis in the salivary glands. These results highlight a cascade of
      fibrosis in chronic GVHD; macrophage production of transforming growth factor
      beta mediates fibroblast differentiation to HSP47+ myofibroblasts that produce
      collagen. VA-lip HSP47 represent a novel strategy to modulate fibrosis in chronic
      GVHD by targeting HSP47+ myofibroblasts without inducing immunosuppression.

PMID- 29363542
TI  - Ruxolitinib protects skin stem cells and maintains skin homeostasis in murine
      graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) is the major complication after allogeneic stem
      cell transplantation (SCT). Emerging evidence indicates that GVHD leads to injury
      of intestinal stem cells. However, it remains to be investigated whether skin
      stem cells could be targeted in skin GVHD. Lgr5+ hair follicle stem cells (HFSCs)
      contribute to folliculogenesis and have a multipotent capacity to regenerate all
      epithelial cells in repair. We studied the fate of Lgr5+ HFSCs after SCT and
      explored the novel treatment to protect Lgr5+ HFSCs against GVHD using murine
      models of SCT. We found that GVHD reduced Lgr5+ HFSCs in association with
      impaired hair regeneration and wound healing in the skin after SCT. Topical
      corticosteroids, a standard of care for a wide range of skin disorders including
      GVHD, damaged HFSCs and failed to improve skin homeostasis, despite of their anti
      inflammatory effects. In contrast, JAK1/2 inhibitor ruxolitinib significantly
      ameliorated skin GVHD, protected Lgr5+ HFSCs, and restored hair regeneration and
      wound healing after SCT. We, for the first time, found that GVHD targets Lgr5+
      HFSCs and that topical ruxolitinib represents a novel strategy to protect skin
      stem cells and maintain skin homeostasis in GVHD.

PMID- 29363540
TI  - Remodeling of the malaria parasite and host human red cell by vesicle
      amplification that induces artemisinin resistance.
AB  - Artemisinin resistance threatens worldwide malaria control and elimination.
      Elevation of phosphatidylinositol-3-phosphate (PI3P) can induce resistance in
      blood stages of Plasmodium falciparum The parasite unfolded protein response
      (UPR) has also been implicated as a proteostatic mechanism that may diminish
      artemisinin-induced toxic proteopathy. How PI3P acts and its connection to the
      UPR remain unknown, although both are conferred by mutation in P falciparum
      Kelch13 (K13), the marker of artemisinin resistance. Here we used
      cryoimmunoelectron microscopy to show that K13 concentrates at PI3P
      tubules/vesicles of the parasite's endoplasmic reticulum (ER) in infected red
      cells. K13 colocalizes and copurifies with the major virulence adhesin PfEMP1.
      The PfEMP1-K13 proteome is comprehensively enriched in multiple proteostasis
      systems of protein export, quality control, and folding in the ER and cytoplasm
      and UPR. Synthetic elevation of PI3P that induces resistance in absence of K13
      mutation also yields signatures of proteostasis and clinical resistance. These
      findings imply a key role for PI3P-vesicle amplification as a mechanism of
      resistance of infected red cells. As validation, the major resistance mutation
      K13C580Y quantitatively increased PI3P tubules/vesicles, exporting them
      throughout the parasite and the red cell. Chemical inhibitors and fluorescence
      microscopy showed that alterations in PfEMP1 export to the red cell and
      cytoadherence of infected cells to a host endothelial receptor are features of
      multiple K13 mutants. Together these data suggest that amplified PI3P vesicles
      disseminate widespread proteostatic capacity that may neutralize artemisinins
      toxic proteopathy and implicate a role for the host red cell in artemisinin
      resistance. The mechanistic insights generated will have an impact on malaria
      drug development.

PMID- 29363543
TI  - Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin
      Induced ERalpha+ Mammary Carcinomas.
AB  - Although antiestrogen therapies are successful in many patients with estrogen
      receptor alpha-positive (ERalpha+) breast cancer, 25% to 40% fail to respond.
      Although multiple mechanisms underlie evasion of these treatments, including
      tumor heterogeneity and drug-resistant cancer stem cells (CSC), further
      investigations have been limited by the paucity of preclinical ERalpha+ tumor
      models. Here, we examined a mouse model of prolactin-induced aggressive ERalpha+
      breast cancer, which mimics the epidemiologic link between prolactin exposure and
      increased risk for metastatic ERalpha+ tumors. Like a subset of ERalpha+ patient
      cancers, the prolactin-induced adenocarcinomas contained two major tumor
      subpopulations that expressed markers of normal luminal and basal epithelial
      cells. CSC activity was distributed equally across these two tumor
      subpopulations. Treatment with the selective estrogen receptor downregulator
      (SERD), ICI 182,780 (ICI), did not slow tumor growth, but induced adaptive
      responses in CSC activity, increased markers of plasticity including target gene
      reporters of Wnt/Notch signaling and epithelial-mesenchymal transition, and
      increased double-positive (K8/K5) cells. In primary tumorsphere cultures, ICI
      stimulated CSC self-renewal and was able to overcome the dependence of self
      renewal upon Wnt or Notch signaling individually, but not together. Our findings
      demonstrate that treatment of aggressive mixed lineage ERalpha+ breast cancers
      with a SERD does not inhibit growth, but rather evokes tumor cell plasticity and
      regenerative CSC activity, predicting likely negative impacts on patient tumors
      with these characteristics.Significance: This study suggests that treatment of a
      subset of ERalpha+ breast cancers with antiestrogen therapies may not only fail
      to slow growth but also promote aggressive behavior by evoking tumor cell
      plasticity and regenerative CSC activity. Cancer Res; 78(7); 1672-84. (c)2018
      AACR.

PMID- 29363545
TI  - Downregulation of Membrane Trafficking Proteins and Lactate Conditioning
      Determine Loss of Dendritic Cell Function in Lung Cancer.
AB  - Restoring antigen presentation for efficient and durable activation of tumor
      specific CD8+ T-cell responses is pivotal to immunotherapy, yet the mechanisms
      that cause subversion of dendritic cell (DC) functions are not entirely
      understood, limiting the development of targeted approaches. In this study, we
      show that bona fide DCs resident in lung tumor tissues or DCs exposed to factors
      derived from whole lung tumors become refractory to endosomal and cytosolic
      sensor stimulation and fail to secrete IL12 and IFNI. Tumor-conditioned DC
      exhibited downregulation of the SNARE VAMP3, a regulator of endosomes trafficking
      critical for cross-presentation of tumor antigens and DC-mediated tumor
      rejection. Dissection of cell-extrinsic suppressive pathways identified lactic
      acid in the tumor microenvironment as sufficient to inhibit type-I IFN downstream
      of TLR3 and STING. DC conditioning by lactate also impacted adaptive function,
      accelerating antigen degradation and impairing cross-presentation. Importantly,
      DCs conditioned by lactate failed to prime antitumor responses in vivo These
      findings provide a new mechanistic viewpoint to the concept of DC suppression and
      hold potential for future therapeutic approaches.Significance: These findings
      provide insight into the cell-intrinsic and cell-extrinsic mechanisms that cause
      loss of presentation of tumor-specific antigens in lung cancer tissues. Cancer
      Res; 78(7); 1685-99. (c)2018 AACR.

PMID- 29363544
TI  - Tumor-Stroma IL1beta-IRAK4 Feedforward Circuitry Drives Tumor Fibrosis,
      Chemoresistance, and Poor Prognosis in Pancreatic Cancer.
AB  - Targeting the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC)
      holds promise to augment the effect of chemotherapy, but success in the clinic
      has thus far been limited. Preclinical mouse models suggest that near-depletion
      of cancer-associated fibroblasts (CAF) carries a risk of accelerating PDAC
      progression, underscoring the need to concurrently target key signaling
      mechanisms that drive the malignant attributes of both CAF and PDAC cells. We
      previously reported that inhibition of IL1 receptor-associated kinase 4 (IRAK4)
      suppresses NFkappaB activity and promotes response to chemotherapy in PDAC cells.
      In this study, we report that CAF in PDAC tumors robustly express activated IRAK4
      and NFkappaB. IRAK4 expression in CAF promoted NFkappaB activity, drove tumor
      fibrosis, and supported PDAC cell proliferation, survival, and chemoresistance.
      Cytokine array analysis of CAF and microarray analysis of PDAC cells identified
      IL1beta as a key cytokine that activated IRAK4 in CAF. Targeting IRAK4 or IL1beta
      rendered PDAC tumors less fibrotic and more sensitive to gemcitabine. In clinical
      specimens of human PDAC, high stromal IL1beta expression associated strongly with
      poor overall survival. Together, our studies establish a tumor-stroma IL1beta
      IRAK4 feedforward signal that can be therapeutically disrupted to increase
      chemotherapeutic efficacy in PDAC.Significance: Targeting the IL1beta-IRAK4
      signaling pathway potentiates the effect of chemotherapy in pancreatic cancer.
      Cancer Res; 78(7); 1700-12. (c)2018 AACR.

PMID- 29363546
TI  - Myeloma Cells Are Activated in Bone Marrow Microenvironment by the CD180/MD-1
      Complex, Which Senses Lipopolysaccharide.
AB  - Multiple myeloma (MM) cells acquire dormancy and drug resistance via interaction
      with bone marrow stroma cells (BMSC) in a hypoxic microenvironment. Elucidating
      the mechanisms underlying the regrowth of dormant clones may contribute to
      further improvement of the prognosis of MM patients. In this study, we find that
      the CD180/MD-1 complex, a noncanonical lipopolysaccharide (LPS) receptor, is
      expressed on MM cells but not on normal counterparts, and its abundance is
      markedly upregulated under adherent and hypoxic conditions. Bacterial LPS and
      anti-CD180 antibody, but not other Toll-like receptor ligands, enhanced the
      growth of MM cells via activation of MAP kinases ERK and JNK in positive
      correlation with expression levels of CD180. Administration of LPS significantly
      increased the number of CD180/CD138 double-positive cells in a murine xenograft
      model when MM cells were inoculated with direct attachment to BMSC. Knockdown of
      CD180 canceled the LPS response in vitro and in vivo Promoter analyses identified
      IKZF1 (Ikaros) as a pivotal transcriptional activator of the CD180 gene. Both
      cell adhesion and hypoxia activated transcription of the CD180 gene by increasing
      Ikaros expression and its binding to the promoter region. Pharmacological
      targeting of Ikaros by the immunomodulatory drug lenalidomide ameliorated the
      response of MM cells to LPS in a CD180-dependent manner in vitro and in vivo
      Thus, the CD180/MD-1 pathway may represent a novel mechanism of growth regulation
      of MM cells in a BM milieu and may be a therapeutic target of preventing the
      regrowth of dormant MM cells.Significance: This study describes a novel mechanism
      by which myeloma cells are regulated in the bone marrow, where drug resistance
      and dormancy can evolve after treatment, with potential therapeutic implications
      for treating this often untreatable blood cancer. Cancer Res; 78(7); 1766-78.
      (c)2018 AACR.

PMID- 29363547
TI  - Keratin 19 Expression in Hepatocellular Carcinoma Is Regulated by Fibroblast
      Derived HGF via a MET-ERK1/2-AP1 and SP1 Axis.
AB  - Keratin (KRT) 19 is a poor prognostic marker for hepatocellular carcinoma (HCC);
      however, regulatory mechanisms underlying its expression remain unclear. We have
      previously reported the presence of fibrous tumor stroma in KRT19-positive HCC,
      suggesting that cross-talk between cancer-associated fibroblasts (CAF) and tumor
      epithelial cells could regulate KRT19 expression. This was investigated in this
      study using an in vitro model of paracrine interaction between HCC cell lines
      (HepG2, SNU423) and hepatic stellate cells (HSC), a major source of hepatic
      myofibroblasts. HSCs upregulated transcription and translation of KRT19 in HCC
      cells via paracrine interactions. Mechanistically, hepatocyte growth factor (HGF)
      from HSCs activated c-MET and the MEK-ERK1/2 pathway, which upregulated KRT19
      expression in HCC cells. Furthermore, AP1 (JUN/FOSL1) and SP1, downstream
      transcriptional activators of ERK1/2, activated KRT19 expression in HCC cells. In
      clinical specimens of human HCC (n = 339), HGF and KRT19 protein expression
      correlated with CAF levels. In addition, HGF or MET protein expression was
      associated with FOSL1 and KRT19 expression and was found to be a poor prognostic
      factor. Analysis of data from The Cancer Genome Atlas also revealed KRT19
      expression was closely associated with CAF and MET-mediated signaling activities.
      These results provide insights into the molecular background of KRT19-positive
      HCC that display an aggressive phenotype.Significance: These findings reveal
      KRT19 expression in hepatocellular carcinoma is regulated by cross-talk between
      cancer-associated fibroblasts and HCC cells, illuminating new therapeutic targets
      for this aggressive disease. Cancer Res; 78(7); 1619-31. (c)2018 AACR.

PMID- 29363549
TI  - Communication about the impending death of patients with cancer to the family: a
      nationwide survey.
AB  - OBJECTIVES: Explanation about the impending death of imminently dying patients
      with cancer is important for their families. However, little is known about how
      clinicians explain impending death and how families perceive the explanation. We
      aimed to clarify bereaved families' perception of the need for improvements in
      the explanation about impending death and to explore the factors contributing to
      the need. METHODS: In a nationwide survey of 818 bereaved families of patients
      with cancer admitted to inpatient hospices in Japan, we evaluated family
      perceived need for improvements in the explanation about impending death and
      families' experiences of the explanation. RESULTS: Among all the participants
      (n=516, 63%), 35 (6.8%), 123 (24%) and 297 (58%) families felt that
      much/considerable, some and no improvements were needed, respectively.
      Independent determinants of the need were a younger patient age (OR=0.97; 95% CI
      0.95 to 0.99; P=0.009); not receiving an 'explicit explanation about physical
      signs of impending death' (OR=0.67; 95% CI 0.51 to 0.88; P=0.004); not receiving
      an 'explanation of how long the patient and family could talk' (OR=0.67; 95% CI
      0.51 to 0.88; P<0.001); receiving an 'excessive warning of impending death'
      (OR=1.45; 95% CI 1.03 to 2.03; P=0.033) and having a feeling of 'uncertainty
      caused by vague explanations about future changes' (OR=1.77; 95% CI 1.38 to 2.27;
      P<0.001). CONCLUSIONS: Nearly a third of the bereaved families perceived some
      need to improve the explanation about impending death. To better help
      patients/families prepare for their end-of-life, clinicians should recognise and
      explain various impending death signs; find a balance between detailed
      explanation and excessive warning and address how long they could talk in the
      remaining time.

PMID- 29363548
TI  - Fc-Mediated Anomalous Biodistribution of Therapeutic Antibodies in
      Immunodeficient Mouse Models.
AB  - A critical benchmark in the development of antibody-based therapeutics is
      demonstration of efficacy in preclinical mouse models of human disease, many of
      which rely on immunodeficient mice. However, relatively little is known about how
      the biology of various immunodeficient strains impacts the in vivo fate of these
      drugs. Here we used immunoPET radiotracers prepared from humanized, chimeric, and
      murine mAbs against four therapeutic oncologic targets to interrogate their
      biodistribution in four different strains of immunodeficient mice bearing lung,
      prostate, and ovarian cancer xenografts. The immunodeficiency status of the mouse
      host as well as both the biological origin and glycosylation of the antibody
      contributed significantly to the anomalous biodistribution of therapeutic
      monoclonal antibodies in an Fc receptor-dependent manner. These findings may have
      important implications for the preclinical evaluation of Fc-containing
      therapeutics and highlight a clear need for biodistribution studies in the early
      stages of antibody drug development.Significance: Fc/FcgammaR-mediated
      immunobiology of the experimental host is a key determinant to preclinical in
      vivo tumor targeting and efficacy of therapeutic antibodies. Cancer Res; 78(7);
      1820-32. (c)2018 AACR.

PMID- 29363550
TI  - Bereaved caregivers of patients with high-grade glioma: a systematic review.
AB  - OBJECTIVE: Caregivers to patients with primary malignant brain tumours neglect
      their own physical and emotional needs during the disease trajectory. The aim of
      the systematic review was to explore how informal caregivers of patients with
      primary malignant brain tumour (high-grade glioma (HGG)) experience and manage
      their life situation after the death of the patient. METHODS: A systematic
      literature search was carried out in December 2016 and revised in September 2017.
      The following six databases were searched: PubMed, Cumulative Index of Nursing
      and Allied Health Literature, Excerpta Medica database, Scopus, PsycINFO and The
      Social Sciences Citation Index. Studies eligible for inclusion met the following
      criteria: (1) included bereaved caregivers to patients diagnosed with HGG >=18
      years, (2) described the caregiver's perspective at post bereavement (3) had been
      peer-reviewed. The papers included were assessed for methodological quality using
      the Critical Appraisal Skills Programme. RESULTS: Four qualitative articles,
      published from 2004 to 2015, met the eligibility criteria. Bereaved informal
      caregivers expressed profound grief and had unmet needs and questions related to
      the disease and their role as caregiver. Moreover, they experienced depressive
      symptoms and fatigue, resulting in a reduced work capability and social network.
      CONCLUSIONS: We conclude that bereaved informal caregivers experience
      psychosocial consequences and emotional reactions after bereavement, resulting in
      feelings of isolation and loneliness. This review identified limited evidence on
      how the bereaved caregivers prefer to be supported, and further study is
      warranted. We suggest incorporating systematic information on bereavement in
      clinical practice and a cooperation across sectors.

PMID- 29363551
TI  - Beyond Genomic Prediction: Combining Different Types of omics Data Can Improve
      Prediction of Hybrid Performance in Maize.
AB  - The ability to predict the agronomic performance of single-crosses with high
      precision is essential for selecting superior candidates for hybrid breeding.
      With recent technological advances, thousands of new parent lines, and,
      consequently, millions of new hybrid combinations are possible in each breeding
      cycle, yet only a few hundred can be produced and phenotyped in multi-environment
      yield trials. Well established prediction approaches such as best linear unbiased
      prediction (BLUP) using pedigree data and whole-genome prediction using genomic
      data are limited in capturing epistasis and interactions occurring within and
      among downstream biological strata such as transcriptome and metabolome. Because
      mRNA and small RNA (sRNA) sequences are involved in transcriptional,
      translational and post-translational processes, we expect them to provide
      information influencing several biological strata. However, using sRNA data of
      parent lines to predict hybrid performance has not yet been addressed. Here, we
      gathered genomic, transcriptomic (mRNA and sRNA) and metabolomic data of parent
      lines to evaluate the ability of the data to predict the performance of untested
      hybrids for important agronomic traits in grain maize. We found a considerable
      interaction for predictive ability between predictor and trait, with mRNA data
      being a superior predictor for grain yield and genomic data for grain dry matter
      content, while sRNA performed relatively poorly for both traits. Combining mRNA
      and genomic data as predictors resulted in high predictive abilities across both
      traits and combining other predictors improved prediction over that of the
      individual predictors alone. We conclude that downstream "omics" can complement
      genomics for hybrid prediction, and, thereby, contribute to more efficient
      selection of hybrid candidates.

PMID- 29363552
TI  - Probing the Mechanism of Receptor Activity-Modifying Protein Modulation of GPCR
      Ligand Selectivity through Rational Design of Potent Adrenomedullin and
      Calcitonin Gene-Related Peptide Antagonists.
AB  - Binding of the vasodilator peptides adrenomedullin (AM) and calcitonin gene
      related peptide (CGRP) to the class B G protein-coupled receptor calcitonin
      receptor-like receptor (CLR) is modulated by receptor activity-modifying proteins
      (RAMPs). RAMP1 favors CGRP, whereas RAMP2 and RAMP3 favor AM. Crystal structures
      of peptide-bound RAMP1/2-CLR extracellular domain (ECD) heterodimers suggested
      RAMPs alter ligand preference through direct peptide contacts and allosteric
      modulation of CLR. Here, we probed this dual mechanism through rational structure
      guided design of AM and CGRP antagonist variants. Variants were characterized for
      binding to purified RAMP1/2-CLR ECD and for antagonism of the full-length CGRP
      (RAMP1:CLR), AM1 (RAMP2:CLR), and AM2 (RAMP3:CLR) receptors. Short nanomolar
      affinity AM(37-52) and CGRP(27-37) variants were obtained through substitutions
      including AM S45W/Q50W and CGRP K35W/A36S designed to stabilize their beta-turn.
      K46L and Y52F substitutions designed to exploit RAMP allosteric effects and
      direct peptide contacts, respectively, yielded AM variants with selectivity for
      the CGRP receptor over the AM1 receptor. AM(37-52) S45W/K46L/Q50W/Y52F exhibited
      nanomolar potency at the CGRP receptor and micromolar potency at AM1 A 2.8-A
      resolution crystal structure of this variant bound to the RAMP1-CLR ECD confirmed
      that it bound as designed. CGRP(27-37) N31D/S34P/K35W/A36S exhibited potency and
      selectivity comparable to the traditional antagonist CGRP(8-37). Giving this
      variant the ability to contact RAMP2 through the F37Y substitution increased
      affinity for AM1, but it still preferred the CGRP receptor. These potent peptide
      antagonists with altered selectivity inform the development of AM/CGRP-based
      pharmacological tools and support the hypothesis that RAMPs alter CLR ligand
      selectivity through allosteric effects and direct peptide contacts.

PMID- 29363553
TI  - Hematopoietic stem/progenitor cell senescence is associated with altered
      expression profiles of cellular memory-involved gene.
AB  - To evaluate the contributions of cellular memory mechanisms to hematopoietic
      stem/progenitor cell (HSPC) senescence. HSPCs (Lin-CD117+, hereafter referred to
      as HSPC) were separated from young (6-week-old) and aged (18-month-old) mice
      using Magnetic Activated Cell Sorting (MACS). Cell cycle distribution of HSPCs
      was determined using flow cytometry. The mixed colony forming unit (CFU-Mix)
      assay was used to study the HSPCs' ability to proliferate. The mRNA expression
      levels of cellular memory-implicated PCG family (enhancer of zeste homolog 2
      (Ezh2), B lymphoma mo-MLV insertion region 1 (Bmi-1), embryonic ectoderm
      development (Eed), melanoma nuclear protein 18 (Mel18), Mph1/polyhomeotic-like
      protein 1 (Rae-28)) and Trithorax group (TrxG) family (mixed lineage leukemia
      (Mll), thioredoxin (Trx)) were determined by quantitative real-time PCR. We
      obtained highly purified populations of mouse HSPCs (Lin-CD117+) (92.2 +/- 4.5%
      CD117+). The percentage of HSPCs was significantly higher in older mice compared
      with younger control mice and the percentage of SA-beta-galactosidase positive
      cells was significantly higher in HSPCs isolated from older mice (P<0.05). The
      percentage of HSPCs in G0/G1 was significantly higher in older mice compared with
      younger control mice (52.0 compared with 47.1%), indicating increased cell cycle
      arrest in senescent HSPCs. The amount of CFU-Mix was significantly decreased in
      aged group (13.8 compared with 40.0), indicating a diminished ability to
      proliferate in senescent HSPCs. Ezh1, Bmi-1, Eed, Rae-28 gene mRNA expression was
      significantly lower in HSPCs from older mice compared to younger controls, while
      Mel18 mRNA expression was significantly higher in HSPCs from older mice (P<0.05).
      The expression of genes associated with cellular memory is altered in senescent
      (Lin- CD117+) HSPCs, which may affect the potential plasticity of aged
      hematopoietic stem cells (HSCs) and thereby contribute to senescence-associated
      disease processes.

PMID- 29363554
TI  - Insight into the molecular mechanism of miR-192 regulating Escherichia coli
      resistance in piglets.
AB  - MicroRNAs (miRNAs) have important roles in many cellular processes, including
      cell proliferation, growth and development, and disease control. Previous study
      demonstrated that the expression of two highly homologous miRNAs (miR-192 and miR
      215) was up-regulated in weaned piglets with Escherichia coli F18 infection.
      However, the potential molecular mechanism of miR-192 in regulating E. coli
      infection remains unclear in pigs. In the present study, we analyzed the
      relationship between level of miR-192 and degree of E. coli resistance using
      transcription activator-like effector nuclease (TALEN), in vitro bacterial
      adhesion assays, and target genes research. A TALEN expression vector that
      specifically recognizes the pig miR-192 was constructed and then monoclonal
      epithelial cells defective in miR-192 were established. We found that miR-192
      knockout led to enhance the adhesion ability of the E. coli strains F18ab, F18ac
      and K88ac, meanwhile increase the expression of target genes (DLG5 and ALCAM) by
      qPCR and Western blotting analysis. The results suggested that miR-192 and its
      key target genes (DLG5 and ALCAM) could have a key role in E. coli infection.
      Based on our findings, we propose that further investigation of miR-192 function
      is likely to lead to insights into the molecular mechanisms of E. coli infection.

PMID- 29363556
TI  - A diagnostic conundrum.

PMID- 29363557
TI  - Neurosarcoidosis associated with intracerebral haemorrhage: a challenge in
      diagnosis and management.
AB  - Sarcoidosis is an idiopathic multisystem granulomatous disorder of unknown cause.
      Nervous system involvement (central and/or peripheral) is uncommon, developing in
      5%-10%. The presenting symptoms are variable, reflecting the level of
      involvement, and frequently fluctuate and progress. Diagnosing neurosarcoidosis
      in people with previously confirmed systemic disease may be relatively
      straightforward, but diagnosing primary neurosarcoidosis is challenging. Managing
      neurosarcoidosis is primarily consensus based; corticosteroid is its mainstay,
      alongside corticosteroid-sparing agents and emerging novel therapies. We describe
      a 39-year-old woman who presented with cranial neuropathy. Serial imaging,
      cerebrospinal fluid sampling and tissue biopsy gave a diagnosis of probable
      neurosarcoidosis. Her clinical course was complicated by intracerebral
      haemorrhage following intravenous corticosteroids for neurological relapse. This
      is a very rare complication of neurosarcoidosis; we discuss its possible causes
      and suggest ways to reduce its risk.

PMID- 29363555
TI  - Conservation, evolution, and regulation of splicing during prefrontal cortex
      development in humans, chimpanzees, and macaques.
AB  - Changes in splicing are known to affect the function and regulation of genes. We
      analyzed splicing events that take place during the postnatal development of the
      prefrontal cortex in humans, chimpanzees, and rhesus macaques based on data
      obtained from 168 individuals. Our study revealed that among the 38,822
      quantified alternative exons, 15% are differentially spliced among species, and
      more than 6% splice differently at different ages. Mutations in splicing acceptor
      and/or donor sites might explain more than 14% of all splicing differences among
      species and up to 64% of high-amplitude differences. A reconstructed trans
      regulatory network containing 21 RNA-binding proteins explains a further 4% of
      splicing variations within species. While most age-dependent splicing patterns
      are conserved among the three species, developmental changes in intron retention
      are substantially more pronounced in humans.

PMID- 29363558
TI  - Psychosocial job stressors and suicidality: can stress at work lead to suicide?

PMID- 29363559
TI  - Sidt2 regulates hepatocellular lipid metabolism through autophagy.
AB  - SID1 transmembrane family member 2 (Sidt2) is an integral lysosomal membrane
      protein. To investigate its explicit function, we generated a global Sidt2
      knockout mouse model (Sidt2-/-). Compared with the littermate controls, Sidt2-/-
      mice exhibited a remarkable accumulation of lipid droplets in liver. First, it
      was observed that food consumption, hepatocyte fatty acid uptake and de novo
      lipogenesis, hepatocyte lipolysis, and TG secretion in the form of very low
      density lipoprotein were comparable between Sidt2-/- and WT mice. However, the
      hepatic beta-oxidation of fatty acids decreased significantly as revealed by a
      low level of serum beta-hydroxybutyrate in the Sidt2-/- mice along with normal
      mRNA expression of genes involved in fatty acid oxidation. In addition, the
      classical autophagy pathway marker proteins, p62 and LC3-II, increased in liver,
      along with compromised autophagic flux in primary hepatocytes, indicating a block
      of autophagosome maturation due to Sidt2 deficiency, which was also supported by
      electron microscopy image analysis both in livers and in primary hepatocytes from
      Sidt2-/- mice. It was concluded that Sidt2 plays an important role in mouse
      hepatic lipid homeostasis by regulating autophagy at the terminal stage.

PMID- 29363561
TI  - Completion Rate and Safety of Tuberculosis Infection Treatment With Shorter
      Regimens.
AB  - BACKGROUND: The traditional treatment of tuberculosis (TB) infection (9 months of
      daily isoniazid [9H]) is safe but completion rates of <50% are reported. Shorter
      regimens (3 months of once-weekly isoniazid and rifapentine [3HP] or 4 months of
      daily rifampin [4R]) are associated with improved adherence in adults. METHODS:
      This was a retrospective cohort study (2014-2017) of children (0-18 years old)
      seen at a children's TB clinic in a low-incidence nation. We compared the
      frequency of completion and adverse events (AEs) in children receiving 3HP, 4R,
      and 9H; the latter 2 regimens could be administered by families (termed self
      administered therapy [SAT]) or as directly observed preventive therapy (DOPT);
      3HP was always administered under DOPT. RESULTS: TB infection treatment was
      started in 667 children: 283 (42.4%) 3HP, 252 (37.8%) 9H, and 132 (19.8%) 4R.
      Only 52% of children receiving 9H via SAT completed therapy. Children receiving
      3HP were more likely to complete therapy than the 9H (SAT) group (odds ratio [OR]
      27.4, 95% confidence interval [CI]: 11.8-63.7). Multivariate analyses found
      receipt of medication under DOPT (OR: 5.72, 95% CI: 3.47-9.43), increasing age
      (OR: 1.09, 95% CI: 1.02-1.17), and the absence of any AE (OR: 1.70, 95% CI: 0.26
      0.60) to be associated with completing therapy. AEs were more common in the 9H
      group (OR: 2.51, 95% CI: 1.48-4.32). Two (0.9%) children receiving 9H developed
      hepatotoxicity; no child receiving 3HP or 4R developed hepatotoxicity.
      CONCLUSIONS: Shorter regimens are associated with increased completion rates and
      fewer AEs than 9H.

PMID- 29363560
TI  - Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR
      Cas9 gene perturbation screens.
AB  - High-content imaging using automated microscopy and computer vision allows
      multivariate profiling of single-cell phenotypes. Here, we present methods for
      the application of the CISPR-Cas9 system in large-scale, image-based, gene
      perturbation experiments. We show that CRISPR-Cas9-mediated gene perturbation can
      be achieved in human tissue culture cells in a timeframe that is compatible with
      image-based phenotyping. We developed a pipeline to construct a large-scale
      arrayed library of 2,281 sequence-verified CRISPR-Cas9 targeting plasmids and
      profiled this library for genes affecting cellular morphology and the subcellular
      localization of components of the nuclear pore complex (NPC). We conceived a
      machine-learning method that harnesses genetic heterogeneity to score gene
      perturbations and identify phenotypically perturbed cells for in-depth
      characterization of gene perturbation effects. This approach enables genome-scale
      image-based multivariate gene perturbation profiling using CRISPR-Cas9.

PMID- 29363562
TI  - The Physician Payments Sunshine Act: Implications and Predictions.

PMID- 29363563
TI  - A Connection between Lysine and Serotonin Metabolism in Rice Endosperm.
AB  - Cereal endosperms produce a vast array of metabolites, including the essential
      amino acid lysine (Lys). Enhanced accumulation of Lys has been achieved via
      metabolic engineering in cereals, but the potential connection between metabolic
      engineering and Lys fortification is unclear. In mature seeds of engineered High
      Free Lysine (HFL) rice (Oryza sativa), the endosperm takes on a characteristic
      dark-brown appearance. In this study, we use an integrated metabolomic and
      transcriptomic approach combined with functional validation to elucidate the key
      metabolites responsible for the dark-brown phenotype. Importantly, we found that
      serotonin biosynthesis was elevated dramatically and closely linked with dark
      brown endosperm color in HFL rice. A functional connection between serotonin and
      endosperm color was confirmed via overexpression of TDC3, a key enzyme of
      serotonin biosynthesis. Furthermore, we show that both the jasmonate signaling
      pathway and TDC expression were strongly induced in the late stage of endosperm
      development of HFL rice, coinciding with serotonin accumulation and dark-brown
      pigmentation. We propose a model for the metabolic connection between Lys and
      serotonin metabolism in which elevated 2-aminoadipate from Lys catabolism may
      play a key role in the connection between the jasmonate signaling pathway,
      serotonin accumulation, and the brown phenotype in rice endosperm. Our data
      provide a deeper understanding of amino acid metabolism in rice. In addition, the
      finding that both Lys and serotonin accumulate in HFL rice grains should promote
      efforts to create a nutritionally favorable crop.

PMID- 29363565
TI  - Influences: Growing up in Yale Physiology.

PMID- 29363564
TI  - A Pectin Methylesterase Inhibitor Enhances Resistance to Verticillium Wilt.
AB  - Pectins are major components of the primary plant cell wall, which functions as
      the primary barrier against pathogens. Pectin methylesterases (PMEs) catalyze the
      demethylesterification of the homogalacturonan domains of pectin in the plant
      cell wall. Their activity is regulated by PME inhibitors (PMEIs). Here, we
      provide evidence that the pectin methylesterase-inhibiting protein GhPMEI3 from
      cotton (Gossypium hirsutum) functions in plant responses to infection by the
      fungus Verticillium dahliae GhPMEI3 interacts with PMEs and regulates the
      expression of a specific fungal polygalacturonase (VdPG1). Ectopic expression of
      GhPMEI3 increased pectin methyl esterification and limited fungal disease in
      cotton, while also modulating root elongation. Enzymatic analyses revealed that
      GhPMEI3 efficiently inhibited the activity of cotton GhPME2/GhPME31. Experiments
      using transgenic Arabidopsis (Arabidopsis thaliana) plants expressing the GhPMEI3
      gene under the control of the CaMV 35S promoter revealed that GhPMEI3 inhibits
      the endogenous PME activity in vitro. Moreover, the enhanced resistance to V.
      dahliae was associated with altered VdPG1 expression. Virus-induced silencing of
      GhPMEI3 resulted in increased susceptibility to V. dahliae Further, we
      investigated the interaction between GhPMEI3 and GhPME2/GhPME31 using inhibition
      assays and molecular docking simulations. The peculiar structural features of
      GhPMEI3 were responsible for the formation of a 1:1 stoichiometric complex with
      GhPME2/GhPME31. Together, these results suggest that GhPMEI3 enhances resistance
      to Verticillium wilt. Moreover, GhPMEI3-GhPMEs interactions would be needed
      before drawing the correlation between structure-function and are crucial for
      plant development against the ever-evolving fungal pathogens.

PMID- 29363566
TI  - The founding of Journal of General Physiology: Membrane permeation and ion
      selectivity.
AB  - This essay begins with a description of the founding years of Journal of General
      Physiology (JGP) and a historical overview of the content of the journal. It then
      turns to key conceptual articles published in JGP that advanced the field of
      membrane permeation and ion selectivity. Much of this information comes from
      reading the online archives of JGP and searches in PubMed.

PMID- 29363567
TI  - Disruption of female reproductive function by endotoxins.
AB  - Endotoxemia can be caused by obesity, environmental chemical exposure, abiotic
      stressors and bacterial infection. Circumstances that deleteriously impact
      intestinal barrier integrity can induce endotoxemia, and controlled experiments
      have identified negative impacts of lipopolysaccharide (LPS; an endotoxin
      mimetic) on folliculogenesis, puberty onset, estrus behavior, ovulation, meiotic
      competence, luteal function and ovarian steroidogenesis. In addition, neonatal
      LPS exposures have transgenerational female reproductive impacts, raising concern
      about early life contacts to this endogenous reproductive toxicant. Aims of this
      review are to identify physiological stressors causing endotoxemia, to highlight
      potential mechanism(s) by which LPS compromises female reproduction and identify
      knowledge gaps regarding how acute and/or metabolic endotoxemia influence(s)
      female reproduction.

PMID- 29363568
TI  - FKBP51 regulates decidualization through Ser473 dephosphorylation of AKT.
AB  - Defective decidualization of human endometrial stromal cells (ESCs) has recently
      been highlighted as an underlying cause of implantation failure. FK-506-binding
      protein 51 (FKBP51) has been shown to participate in the steroid hormone response
      and the protein kinase B (AKT) regulation process, both of which are important
      pathways involved in decidualization. The objective of the present study was to
      investigate the potential effects and mechanisms of FKBP51 in the regulation of
      ESC decidualization. By performing immunohistochemical staining on an endometrial
      tissue microarray (TMA) derived from normal females, we found that FKBP51
      expression was much higher in the luteal phase than in the follicular phase in
      ESCs. Primary ESCs were isolated from patients to build an in vitro
      decidualization model through co-culture with medroxyprogesterone acetate (MPA)
      and 8-bromoadenosine (cAMP). SC79, a specific AKT activator in various
      physiological and pathological conditions, and shRNA-FKBP51 were used to examine
      the roles of AKT and FKBP51 in decidualization. The Western blot and RT-PCR
      results showed that FKBP51, insulin-like growth factor-binding protein 1 (IGFBP1)
      and prolactin (PRL) expression increased in ESCs treated with MPA + cAMP;
      meanwhile, the level of p-Ser473 AKT (p-S473 AKT) decreased and forkhead box
      protein O1 (FOXO1A) expression increased. Decidualization was inhibited by the
      AKT activator SC79 and the transfection of FKBP51-shRNA by affecting protein
      synthesis, cell morphology, cell growth and cell cycle. Furthermore, this
      inhibition was rescued by FKBP51-cDNA transfection. The results supported that
      FKBP51 promotes decidualization by reducing the Ser473 phosphorylation levels in
      AKT.

PMID- 29363569
TI  - LIFR increases the release of soluble endoglin via the upregulation of MMP14
      expression in preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy-specific disorder that is the main cause of
      maternal and perinatal morbidity and mortality worldwide. Inadequate
      trophoblastic invasion and endothelial dysfunction in the placenta are considered
      the foundation of the pathogenesis of preeclampsia in which soluble endoglin
      (sENG) plays an antiangiogenic role in the development of PE. The leukemia
      inhibitory factor receptor (LIFR) has been widely studied and is highly involved
      in arterial injury in vivo and in the migration of cancer cells in vitro Here, we
      tested the hypothesis that LIFR may be correlated with preeclampsia through its
      regulation of the release of sENG. Our data showed that LIFR protein, the
      expression of which significantly decreased with the progression of pregnancy,
      was located in the syncytiotrophoblast and cytotrophoblast. The LIFR protein
      level was increased in pregnancies with preeclampsia compared with normotensive
      full-term pregnancies. After the overexpression of LIFR in HTR8/SVneo cells, the
      release of sENG as well as the migration and invasion were significantly
      enhanced. Moreover, we also observed that LIFR induced the expression of matrix
      metalloproteinase14 (MMP14) and that the knockdown or inhibition of MMP14
      decreased the release of sENG, as well as increased the LIFR-induced migration
      and invasion of HTR8/SVneo cells. These studies demonstrated that LIFR promoted
      the release of sENG through MMP14 in vitro, which indicates that LIFR may be
      involved in the development of preeclampsia.

PMID- 29363570
TI  - Melatonin reduces oxidative damage in mouse granulosa cells via restraining JNK
      dependent autophagy.
AB  - Oxidative stress-induced granulosa cell (GCs) injury is believed to be a common
      trigger for follicular atresia. Emerging evidence indicates that excessive
      autophagy occurs in mammalian cells with oxidative damage. N-acetyl-5
      methoxytrypamine (melatonin) has been shown to prevent GCs from oxidative injury,
      although the exact mechanism remains to be elucidated. Here, we first
      demonstrated that the suppression of autophagy through the JNK/BCL-2/BECN1
      signaling is engaged in melatonin-mediated GCs protection against oxidative
      damage. Melatonin inhibited the loss of GCs viability, formation of GFP-MAP1LC3B
      puncta, accumulation of MAP1LC3B-II blots, degradation of SQSTM1 and the
      expression of BECN1, which was correlated with impaired activation of JNK during
      oxidative stress. On the other hand, blocking of autophagy and/or JNK also
      reduced the level of H2O2-induced GCs death, but failed to further restore GCs
      viability in the presence of melatonin. Particularly, the suppression of
      autophagy provided no additional protective effects when GCs were pretreated with
      JNK inhibitor and/or melatonin. Importantly, we found that the enhanced
      interaction between BCL-2 and BECN1 might be a responsive mechanism for autophagy
      suppression via the melatonin/JNK pathway. Moreover, blocking the downstream
      antioxidant system of melatonin using specific inhibitors further confirmed a
      direct role of melatonin/JNK/autophagy axis in preserving GCs survival without
      scavenging reactive oxygen species (ROS). Taken together, our findings uncover a
      novel function of melatonin in preventing GCs from oxidative damage by targeting
      JNK-mediated autophagy, which might contribute to develop therapeutic strategies
      for patients with ovulation failure-related disorders.

PMID- 29363571
TI  - Sheep and farm level factors associated with footrot: a longitudinal repeated
      cross-sectional study of sheep on six farms in the UK.
AB  - Footrot is an ovine foot disease of infectious origin and a cause of serious
      welfare and economic compromise in affected animals and flocks. The development
      of footrot in sheep is associated with the infectious agent Dichelobacter
      nodosus, which may invade as a primary pathogen, but the risk of disease is
      increased following damage to the interdigital skin of the foot. In this study,
      we used data from six farms in North Wales collected between June 2012 and
      October 2013 to model the dynamic changes of footrot prevalence over time and
      investigate the association of footrot with multiple farm, management,
      environmental and sheep factors. Footrot prevalence varied widely within and
      between farms and overall varied with season with an increase in prevalence shown
      in late summer and again in the spring. In addition, sheep were more likely to
      have footrot when the flock size was larger, when grazing poached pasture or when
      grazing a longer sward, and yearling sheep were less likely to have footrot when
      compared with lambs and adult sheep. These data may be helpful for advising
      farmers of likely environmental events, risk groups and management practices that
      may increase the probability of sheep developing footrot.

PMID- 29363572
TI  - Cost distribution of bluetongue surveillance and vaccination programmes in
      Austria and Switzerland (2007-2016).
AB  - Bluetongue virus (BTV) is an emerging transboundary disease in Europe, which can
      cause significant production losses among ruminants. The analysis presented here
      assessed the costs of BTV surveillance and vaccination programmes in Austria and
      Switzerland between 2007 and 2016. Costs were compared with respect to time, type
      of programme, geographical area and who was responsible for payment. The total
      costs of the BTV vaccination and surveillance programmes in Austria amounted to
      ?23.6 million, whereas total costs in Switzerland were ?18.3 million. Our
      analysis demonstrates that the costs differed between years and geographical
      areas, both within and between the two countries. Average surveillance costs per
      animal amounted to approximately ?3.20 in Austria compared with ?1.30 in
      Switzerland, whereas the average vaccination costs per animal were ?6.20 in
      Austria and ?7.40 in Switzerland. The comparability of the surveillance costs is
      somewhat limited, however, due to differences in each nation's surveillance (and
      sampling) strategy. Given the importance of the export market for cattle
      production, investments in such programmes are more justified for Austria than
      for Switzerland. The aim of the retrospective assessment presented here is to
      assist veterinary authorities in planning and implementing cost-effective and
      efficient control strategies for emerging livestock diseases.

PMID- 29363573
TI  - Vesicular nucleotide transporter mediates ATP release and migration in
      neutrophils.
AB  - Neutrophils migrate to sites infected by pathogenic microorganisms. This
      migration is regulated by neutrophil-secreted ATP, which stimulates neutrophils
      in an autocrine manner through purinergic receptors on the plasma membrane.
      Although previous studies have shown that ATP is released through channels at the
      plasma membrane of the neutrophil, it remains unknown whether it is also released
      through alternate secretory systems involving vesicular mechanisms. In this
      study, we investigated the possible involvement of vesicular nucleotide
      transporter (VNUT), a key molecule for vesicular storage and nucleotide release,
      in ATP secretion from neutrophils. RT-PCR and Western blotting analysis indicated
      that VNUT is expressed in mouse neutrophils. Immunohistochemical analysis
      indicated that VNUT mainly colocalized with matrix metalloproteinase-9 (MMP-9), a
      marker of tertiary granules, which are secretory organelles. In mouse
      neutrophils, ATP release was inhibited by clodronate, which is a potent VNUT
      inhibitor. Furthermore, neutrophils from VNUT-/- mice did not release ATP and
      exhibited significantly reduced migration in vitro and in vivo These findings
      suggest that tertiary granule-localized VNUT is responsible for vesicular ATP
      release and subsequent neutrophil migration. Thus, these findings suggest an
      additional mechanism through which ATP is released by neutrophils.

PMID- 29363574
TI  - Fibroblast growth factor 2 induces proliferation and fibrosis via SNAI1-mediated
      activation of CDK2 and ZEB1 in corneal endothelium.
AB  - Investigating stimulation of endogenous wound healing in corneal endothelial
      cells (CECs) may help address the global shortage of donor corneas by decreasing
      the number of transplants performed for blindness because of endothelial
      dysfunction. We previously reported that IL-1beta stimulation leads to fibroblast
      growth factor (FGF2) expression, enhancing migration and proliferation of
      mammalian CECs. However, FGF2 also promotes the endothelial-mesenchymal
      transition, which can lead to retrocorneal membrane formation and blindness. This
      prompted us to investigate downstream FGF2 signaling targets that could be
      manipulated to prevent retrocorneal membrane formation. FGF2 stimulation altered
      cell morphology and induced expression of mesenchymal transition marker genes
      such as snail family transcriptional repressor 1 (SNAI1), SNAI2, zinc finger E
      box-binding homeobox 1 (ZEB1), and ZEB2 This, in turn, induced expression of
      fibronectin, vimentin, and type I collagen, and suppressed E-cadherin in CECs in
      vitro and ex vivo siRNA-mediated SNAI1 knockdown revealed that SNAI1 induces ZEB1
      expression, in turn inducing expression of type I collagen, the major component
      of retrocorneal membranes, and of cyclin-dependent kinase 2 (CDK2) and cyclin E1,
      promoting cell proliferation. siRNA-mediated knockdown of SNAI1 or ZEB1, but not
      of CDK2, inhibited FGF2-dependent expression of fibronectin, vimentin, and type I
      collagen and of suppression of E-cadherin expression. We conclude that SNAI1 is a
      key regulator of FGF2-dependent mesenchymal transition in human ex vivo corneal
      endothelium, with ZEB1 regulating type I collagen expression and CDK2 regulating
      cell proliferation. These results suggest that SNAI1 promotes fibrosis and cell
      proliferation in human corneal endothelium through ZEB1 and CDK2.

PMID- 29363575
TI  - A Darier disease mutation relieves kinetic constraints imposed by the tail of
      sarco(endo)plasmic reticulum Ca2+-ATPase 2b.
AB  - The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 2b isoform possesses an
      extended C terminus (SERCA2b tail) forming an 11th transmembrane (TM) helix,
      which slows conformational changes of the Ca2+-pump reaction cycle. Here, we
      report that a Darier disease (DD) mutation of SERCA2b that changes a glutamate to
      a lysine in the cytoplasmic loop between TM8 and TM9 (E917K) relieves these
      kinetic constraints. We analyzed the effects of this mutation on the overall
      reaction and the individual partial reactions of the Ca2+ pump compared with the
      corresponding mutations of the SERCA2a and SERCA1a isoforms, lacking the SERCA2b
      tail. In addition to a reduced affinity for Ca2+, caused by the mutation in all
      three isoforms examined, we observed a unique enhancing effect on the turnover
      rates of ATPase activity and Ca2+ transport for the SERCA2b E917K mutation. This
      relief of kinetic constraints contrasted with inhibitory effects observed for the
      corresponding SERCA2a and SERCA1a (E918K) mutations. These observations indicated
      that the E917K/E918K mutations affect the rate-limiting conformational change in
      isoform-specific ways and that the SERCA2b mutation perturbs the interactions of
      TM11 with other SERCA2b regions. Mutational analysis of an arginine in TM7 that
      interacts with the glutamate in SERCA1a crystal structures suggested that in
      wildtype SERCA2b, the corresponding arginine (Arg-835) may be involved in
      mediating the conformational restriction by TM11. Moreover, the E917K mutation
      may disturb TM11 through the cytoplasmic loop between TM10 and TM11. In
      conclusion, our findings have identified structural elements of importance for
      the kinetic constraints imposed by TM11.

PMID- 29363576
TI  - The long non-coding RNA Gm10768 activates hepatic gluconeogenesis by sequestering
      microRNA-214 in mice.
AB  - Overactivated hepatic gluconeogenesis contributes to the pathogenesis of
      metabolic disorders, including type 2 diabetes. Precise control of hepatic
      gluconeogenesis is thus critical for maintaining whole-body metabolic
      homeostasis. Long non-coding RNAs (lncRNAs) have been shown to play key roles in
      diseases by regulating diverse biological processes, but the function of lncRNAs
      in maintaining normal physiology, particularly glucose homeostasis in the liver,
      remains largely unexplored. We identified a novel liver-enriched long non-coding
      RNA, Gm10768, and examined its expression patterns under pathophysiological
      conditions. We further adopted gain- and loss-of-function strategies to explore
      the effect of Gm10768 on hepatic glucose metabolism and the possible molecular
      mechanism involved. Our results showed that the expression of Gm10768 was
      significantly increased in the liver of fasted mice and was induced by
      gluconeogenic hormonal stimuli. Functionally, overexpression of Gm10768 activated
      hepatic gluconeogenesis in a cell-autonomous manner. In contrast, depletion of
      Gm10768 suppressed hepatic glucose production both in vitro and in vivo
      Adenovirus-mediated hepatic knockdown of Gm10768 improved glucose tolerance and
      hyperglycemia of diabetic db/db mice. Mechanistically, Gm10768 sequestrated
      microRNA-214 (miR-214) to relieve its suppression on activating transcription
      factor 4 (ATF4), a positive regulator of hepatic gluconeogenesis. Taken together,
      we identified Gm10768 as a new lncRNA activating hepatic gluconeogenesis through
      antagonizing miR-214 in mice.

PMID- 29363578
TI  - In Silico Screening Identified Novel Small-molecule Antagonists of PAC1 Receptor.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are
      present in the spinal dorsal horn and dorsal root ganglia, suggesting an
      important role of PACAP signaling systems in the modulation of spinal nociceptive
      transmission. Previously, we found that intrathecal injection of PACAP or
      maxadilan, a selective PACAP type I (PAC1) receptor agonist, induced transient
      aversive responses followed by a long-lasting mechanical allodynia in mice,
      suggesting that PACAP-PAC1 receptor systems are involved in chronic pain and that
      selective PAC1 antagonists may become a new class of analgesics. Although several
      PAC1 antagonists, such as PACAP 6-38, have been reported, all of them are peptide
      compounds. In the present study, we identified new small-molecule antagonists of
      the PAC1 receptor using in silico screening and in vitro/vivo pharmacological
      assays. The identified small-molecule compounds, named PA-8 and PA-9, dose
      dependently inhibited the phosphorylation of CREB induced by PACAP in PAC1-, but
      not VPAC1- or VPAC2-receptor-expressing CHO cells. PA-8 and PA-9 also dose
      dependently inhibited PACAP-induced cAMP elevation with an IC50 of 2.0 and 5.6
      nM, respectively. In vivo pharmacological assays showed that intrathecal
      injection of these compounds blocked the induction of PACAP-induced aversive
      responses and mechanical allodynia in mice. In contrast, the compounds when
      administered alone exerted neither agonistic nor algesic actions in the in
      vitro/vivo assays. The compounds identified in the present study are new and the
      first small-molecule antagonists of the PAC1 receptor; they may become seed
      compounds for developing novel analgesics.

PMID- 29363577
TI  - The arrestin-1 finger loop interacts with two distinct conformations of active
      rhodopsin.
AB  - Signaling of the prototypical G protein-coupled receptor (GPCR) rhodopsin through
      its cognate G protein transducin (Gt) is quenched when arrestin binds to the
      activated receptor. Although the overall architecture of the rhodopsin/arrestin
      complex is known, many questions regarding its specificity remain unresolved.
      Here, using FTIR difference spectroscopy and a dual pH/peptide titration assay,
      we show that rhodopsin maintains certain flexibility upon binding the "finger
      loop" of visual arrestin (prepared as synthetic peptide ArrFL-1). We found that
      two distinct complexes can be stabilized depending on the protonation state of
      E3.49 in the conserved (D)ERY motif. Both complexes exhibit different interaction
      modes and affinities of ArrFL-1 binding. The plasticity of the receptor within
      the rhodopsin/ArrFL-1 complex stands in contrast to the complex with the C
      terminus of the Gt alpha-subunit (GalphaCT), which stabilizes only one specific
      substate out of the conformational ensemble. However, Gt alpha-subunit binding
      and both ArrFL-1-binding modes involve a direct interaction to conserved R3.50,
      as determined by site-directed mutagenesis. Our findings highlight the importance
      of receptor conformational flexibility and cytoplasmic proton uptake for
      modulation of rhodopsin signaling and thereby extend the picture provided by
      crystal structures of the rhodopsin/arrestin and rhodopsin/ArrFL-1 complexes.
      Furthermore, the two binding modes of ArrFL-1 identified here involve motifs of
      conserved amino acids, which indicates that our results may have elucidated a
      common modulation mechanism of class A GPCR-G protein/-arrestin signaling.

PMID- 29363579
TI  - Repeated Morphine Produces Sensitization to Reward and Tolerance to Antiallodynia
      in Male and Female Rats with Chemotherapy-Induced Neuropathy.
AB  - Paclitaxel is a cancer chemotherapy drug with adverse effects that include
      chemotherapy-induced neuropathic pain (CINP) as well as depression of behavior
      and mood. In the clinical setting, opioids are often used concurrently with or
      after chemotherapy to treat pain related to the cancer or CINP, but repeated
      opioid exposure can also increase the risk of opioid abuse. In this study, male
      and female Sprague-Dawley rats were used to test the hypothesis that repeated 3.2
      mg/kg doses of morphine would induce tolerance to its antinociceptive effects in
      a mechanical sensitivity assay and increased expression of its abuse-related
      rewarding effects in an assay of intracranial self-stimulation (ICSS). Three
      weeks after four injections of vehicle or 2.0 mg/kg of paclitaxel, the initial
      morphine dose-effect curves were determined in both assays. Subsequently, rats
      were treated with 3.2 mg/kg per day morphine for 6 days. On the final day of
      testing, morphine dose-effect curves were redetermined in both assays. On initial
      exposure, morphine produced dose-dependent antiallodynia in the assay of
      mechanical sensitivity, but it produced little or no rewarding effects in the
      assay of ICSS. After 6 days of repeated treatment, morphine antiallodynia
      decreased, and morphine reward increased. Females exhibited greater morphine
      reward on initial exposure than males, but repeated morphine eliminated this sex
      difference. These results suggest that repeated morphine may produce tolerance to
      therapeutically beneficial analgesic effects of morphine but increased
      sensitivity to abuse-related rewarding effects of morphine in subjects treated
      with paclitaxel.

PMID- 29363580
TI  - Deficient Surveillance and Phagocytic Activity of Myeloid Cells Within
      Demyelinated Lesions in Aging Mice Visualized by Ex Vivo Live Multiphoton
      Imaging.
AB  - Aging impairs regenerative processes including remyelination, the synthesis of a
      new myelin sheath. Microglia and other infiltrating myeloid cells such as
      macrophages are essential for remyelination through mechanisms that include the
      clearance of inhibitory molecules within the lesion. Prior studies have shown
      that the quantity of myeloid cells and the clearance of inhibitory myelin debris
      are deficient in aging, contributing to the decline in remyelination efficiency
      with senescence. It is unknown, however, whether the impaired clearance of debris
      is simply the result of the reduced number of phagocytes or if the dynamic
      activity of myeloid cells within the demyelinating plaque also declines with
      aging and this question is relevant to the proper design of therapeutics to
      mobilize myeloid cells for repair. Herein, we describe a high-resolution
      multiphoton ex vivo live imaging protocol that visualizes individual
      myelinated/demyelinated axons and lipid-containing myeloid cells to investigate
      the demyelinated lesion of aging female mice. We found that aging lesions have
      fewer myeloid cells and that these have reduced phagocytosis of myelin. Although
      the myeloid cells are actively migratory within the lesion of young mice and have
      protrusions that seem to survey the environment, this motility and surveillance
      is significantly reduced in aging mice. Our results emphasize the necessity of
      not only increasing the number of phagocytes, but also enhancing their activity
      once they are within demyelinated lesions. The high-resolution live imaging of
      demyelinated lesions can serve as a platform with which to discover
      pharmacological agents that rejuvenate intralesional remodeling that promotes the
      repair of plaques.SIGNIFICANCE STATEMENT The repair of myelin after injury
      depends on myeloid cells that clear debris and release growth factors. As
      organisms age, remyelination becomes less efficient correspondent with fewer
      myeloid cells that populate the lesions. It is unknown whether the dynamic
      activity of cells within lesions is also altered with age. Herein, using high
      resolution multiphoton ex vivo live imaging with several novel features, we
      report that myeloid cells within demyelinated lesions of aging mice have reduced
      motility, surveillance, and phagocytic activity, suggesting an intralesional
      impairment that may contribute to the age-related decline in remyelination
      efficiency. Medications to stimulate deficient aging myeloid cells should not
      only increase their representation, but also enter into lesions to stimulate
      their activity.

PMID- 29363581
TI  - Visual Experience Facilitates BDNF-Dependent Adaptive Recruitment of New Neurons
      in the Postembryonic Optic Tectum.
AB  - Postembryonic brain development is sensitive to environmental input and sensory
      experience, but the mechanisms underlying healthy adaptive brain growth are
      poorly understood. Here, we tested the importance of visual experience on larval
      zebrafish (Danio rerio) postembryonic development of the optic tectum (OT), a
      midbrain structure involved in visually guided behavior. We first characterized
      postembryonic neurogenic growth in OT, in which new neurons are generated along
      the caudal tectal surface and contribute appositionally to anatomical growth.
      Restricting visual experience during development by rearing larvae in dim light
      impaired OT anatomical and neurogenic growth, specifically by reducing the
      survival of new neurons in the medial periventricular gray zone. Neuronal
      survival in the OT was reduced only when visual experience was restricted for the
      first 5 d following new neuron generation, suggesting that tectal neurons exhibit
      an early sensitive period in which visual experience protects these cells from
      subsequent neuronal loss. The effect of dim rearing on neuronal survival was
      mimicked by treatment with an NMDA receptor antagonist early, but not later, in a
      new neuron's life. Both dim rearing and antagonist treatment reduced BDNF
      production in the OT, and supplementing larvae with exogenous BDNF during dim
      rearing prevented neuronal loss, suggesting that visual experience protects new
      tectal neurons through neural activity-dependent BDNF expression. Collectively,
      we present evidence for a sensitive period of neurogenic adaptive growth in the
      larval zebrafish OT that relies on visual experience-dependent
      mechanisms.SIGNIFICANCE STATEMENT Early brain development is shaped by
      environmental factors via sensory input; however, this form of experience
      dependent neuroplasticity is traditionally studied as structural and functional
      changes within preexisting neurons. Here, we found that restricting visual
      experience affects development of the larval zebrafish optic tectum, a midbrain
      structure involved in visually guided behavior, by limiting the survival of newly
      generated neurons. We found that new tectal neurons exhibit a sensitive period
      soon after cell birth in which adequate visual experience, likely mediated by
      neuronal activity driving BDNF production within the tectum, would protect them
      from subsequent neuronal loss over the following week. Collectively, we present
      evidence for neurogenic adaptive tectal growth under different environmental
      lighting conditions.

PMID- 29363582
TI  - Commonalities and Differences in the Substrates Underlying Consolidation of First
      and Second-Order Conditioned Fear.
AB  - Consolidation of newly formed fear memories requires a series of molecular events
      within the basolateral complex of the amygdala (BLA). Once consolidated, new
      information can be assimilated into these established associative networks to
      form higher-order associations. Much is known about the molecular events involved
      in consolidating newly acquired fear memories but little is known about the
      events that consolidate a secondary fear memory. Here, we show that, within the
      male rat BLA, DNA methylation and gene transcription are crucial for
      consolidating both the primary and secondary fear memories. We also show that
      consolidation of the primary, but not the secondary, fear memory requires de novo
      protein synthesis in the BLA. These findings show that consolidation of a fear
      memory and its updating to incorporate new information recruit distinct processes
      in the BLA, and suggest that DNA methylation in the BLA is fundamental to
      consolidation of both types of conditioned fear.SIGNIFICANCE STATEMENT Our data
      provide clear evidence that a different set of mechanisms mediate consolidation
      of learning about cues that signal learned sources of danger (i.e., second-order
      conditioned fear) compared with those involved in consolidation of learning about
      cues that signal innate sources of danger (i.e., first-order conditioned fear).
      These findings carry important implications because second-order learning could
      underlie aberrant fear-related behaviors (e.g., in anxiety disorders) as a
      consequence of neutral secondary cues being integrated into associative fear
      networks established through first-order pairings, and thereby becoming potent
      conditioned reinforcers and predictors of fear. Therefore, our data suggest that
      targeting such second-order conditioned triggers of fear may require
      pharmacological intervention different to that typically used for first-order
      conditioned cues.

PMID- 29363583
TI  - Ephexin1 Is Required for Eph-Mediated Limb Trajectory of Spinal Motor Axons.
AB  - The precise assembly of a functional nervous system relies on the guided
      migration of axonal growth cones, which is made possible by signals transmitted
      to the cytoskeleton by cell surface-expressed guidance receptors. We investigated
      the function of ephexin1, a Rho guanine nucleotide exchange factor, as an
      essential growth-cone guidance intermediary in the context of spinal lateral
      motor column (LMC) motor axon trajectory selection in the limb mesenchyme. Using
      in situ mRNA detection, we first show that ephexin1 is expressed in LMC neurons
      of chick and mouse embryos at the time of spinal motor axon extension into the
      limb. Ephexin1 loss of function and gain of function using in ovo electroporation
      in chick LMC neurons, of either sex, perturbed LMC axon trajectory selection,
      demonstrating an essential role of ephexin1 in motor axon guidance. In addition,
      ephexin1 loss in mice of either sex led to LMC axon trajectory selection errors.
      We also show that ephexin1 knockdown attenuates the growth preference of LMC
      neurites against ephrins in vitro and Eph receptor-mediated retargeting of LMC
      axons in vivo, suggesting that ephexin1 is required in Eph-mediated LMC motor
      axon guidance. Finally, both ephexin1 knockdown and ectopic expression of
      nonphosphorylatable ephexin1 mutant attenuated the retargeting of LMC axons
      caused by Src overexpression, implicating ephexin1 as an Src target in Eph signal
      relay in this context. In summary, our findings demonstrate that ephexin1 is
      essential for motor axon guidance and suggest an important role in relaying
      ephrin:Eph signals that mediate motor axon trajectory selection.SIGNIFICANCE
      STATEMENT The proper development of functioning neural circuits requires precise
      nerve connections among neurons or between neurons and their muscle targets. The
      Eph tyrosine kinase receptors expressed in neurons are important in many contexts
      during neural-circuit formation, such as axon outgrowth, axon guidance, and
      synaptic formation, and have been suggested to be involved in neurodegenerative
      disorders, including amyotrophic lateral sclerosis and Alzheimer's disease. To
      dissect the mechanism of Eph signal relay, we studied ephexin1 gain of function
      and loss of function and found ephexin1 essential for the development of limb
      nerves toward their muscle targets, concluding that it functions as an
      intermediary to relay Eph signaling in this context. Our work could thus shed new
      light on the molecular mechanisms controlling neuromuscular connectivity during
      embryonic development.

PMID- 29363585
TI  - Biased signaling by thyroid-stimulating hormone receptor-specific antibodies
      determines thyrocyte survival in autoimmunity.
AB  - The thyroid-stimulating hormone receptor (TSHR) is a heterotrimeric guanine
      nucleotide-binding protein (G protein)-coupled receptor (GPCR). Autoimmune
      hyperthyroidism, commonly known as Graves' disease (GD), is caused by stimulating
      autoantibodies to the TSHR. We previously described TSHR-specific antibodies
      (TSHR-Abs) in GD that recognize linear epitopes in the cleavage region of the
      TSHR ectodomain (C-TSHR-Abs) and induce thyroid cell apoptosis instead of
      stimulating the TSHR. We found that C-TSHR-Abs entered the cell through clathrin
      mediated endocytosis but did not trigger endosomal maturation and failed to
      undergo normal vesicular sorting and trafficking. We found that stimulating TSHR
      Abs (S-TSHR-Abs) activated Galphas and, to a lesser extent, Galphaq but that C
      TSHR-Abs failed to activate any of the G proteins normally activated in response
      to TSH. Furthermore, specific inhibition of G proteins in the presence of S-TSHR
      mAbs or TSH resulted in a similar failure of endosomal maturation as that caused
      by C-TSHR-mAbs. Hence, whereas S-TSHR-mAbs and TSH contributed to normal
      vesicular trafficking of TSHR through the activation of major G proteins, the C
      TSHR-Abs resulted in GRK2- and beta-arrestin-1-dependent biased signaling, which
      is interpreted as a danger signal by the cell. Our observations suggest that the
      binding of antibodies to different TSHR epitopes may decrease cell survival.
      Antibody-induced cell injury and the response to cell death amplify the loss of
      self-tolerance, which most likely helps to perpetuate GPCR-mediated autoimmunity.

PMID- 29363586
TI  - Guanabenz inhibits TLR9 signaling through a pathway that is independent of
      eIF2alpha dephosphorylation by the GADD34/PP1c complex.
AB  - Endoplasmic reticulum (ER) stress triggers or amplifies inflammatory signals and
      cytokine production in immune cells. Upon the resolution of ER stress, the
      inducible phosphatase 1 cofactor GADD34 promotes the dephosphorylation of the
      initiation factor eIF2alpha, thereby enabling protein translation to resume.
      Several aminoguanidine compounds, such as guanabenz, perturb the eIF2alpha
      phosphorylation-dephosphorylation cycle and protect different cell or tissue
      types from protein misfolding and degeneration. We investigated how
      pharmacological interference with the eIF2alpha pathway could be beneficial to
      treat autoinflammatory diseases dependent on proinflammatory cytokines and type I
      interferons (IFNs), the production of which is regulated by GADD34 in dendritic
      cells (DCs). In mouse and human DCs and B cells, guanabenz prevented the
      activation of Toll-like receptor 9 (TLR9) by CpG oligodeoxynucleotides or DNA
      immunoglobulin complexes in endosomes. In vivo, guanabenz protected mice from CpG
      oligonucleotide-dependent cytokine shock and decreased autoimmune symptom
      severity in a chemically induced model of systemic lupus erythematosus. However,
      we found that guanabenz exerted its inhibitory effect independently of GADD34
      activity on eIF2alpha and instead decreased the abundance of CH25H, a cholesterol
      hydroxylase linked to antiviral immunity. Our results therefore suggest that
      guanabenz and similar compounds could be used to treat type I IFN-dependent
      pathologies and that CH25H could be a therapeutic target to control these
      diseases.

PMID- 29363584
TI  - Neurogenesis during Abstinence Is Necessary for Context-Driven Methamphetamine
      Related Memory.
AB  - Abstinence from methamphetamine addiction enhances proliferation and
      differentiation of neural progenitors and increases adult neurogenesis in the
      dentate gyrus (DG). We hypothesized that neurogenesis during abstinence
      contributes to context-driven drug-seeking behaviors. To test this hypothesis,
      the pharmacogenetic rat model (GFAP-TK rats) was used to conditionally and
      specifically ablate neurogenesis in the DG. Male GFAP-TK rats were trained to
      self-administer methamphetamine or sucrose and were administered the antiviral
      drug valganciclovir (Valcyte) to produce apoptosis of actively dividing GFAP type
      1 stem-like cells to inhibit neurogenesis during abstinence. Hippocampus tissue
      was stained for Ki-67, NeuroD, and DCX to measure levels of neural progenitors
      and immature neurons, and was stained for synaptoporin to determine alterations
      in mossy fiber tracts. DG-enriched tissue punches were probed for CaMKII to
      measure alterations in plasticity-related proteins. Whole-cell patch-clamp
      recordings were performed in acute brain slices from methamphetamine naive
      (controls) and methamphetamine experienced animals (+/-Valcyte). Spontaneous
      EPSCs and intrinsic excitability were recorded from granule cell neurons (GCNs).
      Reinstatement of methamphetamine seeking enhanced autophosphorylation of CaMKII,
      reduced mossy fiber density, and induced hyperexcitability of GCNs. Inhibition of
      neurogenesis during abstinence prevented context-driven methamphetamine seeking,
      and these effects correlated with reduced autophosphorylation of CaMKII,
      increased mossy fiber density, and reduced the excitability of GCNs. Context
      driven sucrose seeking was unaffected. Together, the loss-of-neurogenesis data
      demonstrate that neurogenesis during abstinence assists with methamphetamine
      context-driven memory in rats, and that neurogenesis during abstinence is
      essential for the expression of synaptic proteins and plasticity promoting
      context-driven drug memory.SIGNIFICANCE STATEMENT Our work uncovers a mechanistic
      relationship between neurogenesis in the dentate gyrus and drug seeking. We
      report that the suppression of excessive neurogenesis during abstinence from
      methamphetamine addiction by a confirmed phamacogenetic approach blocked context
      driven methamphetamine reinstatement and prevented maladaptive changes in
      expression and activation of synaptic proteins and basal synaptic function
      associated with learning and memory in the dentate gyrus. Our study is the first
      to demonstrate an interesting and dysfunctional role of adult hippocampal
      neurogenesis during abstinence to drug-seeking behavior in animals self
      administering escalating amounts of methamphetamine. Together, these results
      support a direct role for the importance of adult neurogenesis during abstinence
      in compulsive-like drug reinstatement.

PMID- 29363587
TI  - Intracellular cavity of sensor domain controls allosteric gating of TRPA1
      channel.
AB  - Transient receptor potential ankyrin 1 (TRPA1) is a temperature-sensitive ion
      channel activated by various pungent and irritant compounds that can produce pain
      in humans. Its activation involves an allosteric mechanism whereby electrophilic
      agonists evoke interactions within cytosolic domains and open the channel pore
      through an integrated nexus formed by intracellular membrane proximal regions
      that are densely packed beneath the lower segment of the S1-S4 sensor domain.
      Studies indicate that this part of the channel may contain residues that form a
      water-accessible cavity that undergoes changes in solvation during channel
      gating. We identified conserved polar residues facing the putative lower crevice
      of the sensor domain that were crucial determinants of the electrophilic,
      voltage, and calcium sensitivity of the TRPA1 channel. This part of the sensor
      may also comprise a domain capable of binding to membrane phosphoinositides
      through which gating of the channel is regulated in a state-dependent manner.

PMID- 29363588
TI  - Association between parent mental health and paediatric TBI: epidemiological
      observations from the 1987 Finnish Birth Cohort.
AB  - BACKGROUND: This study examined whether parental mental illness has implications
      for child risk for traumatic brain injuries (TBI). METHOD: Data on 60 069 Finnish
      children born in 1987 and their parents were examined for demographic and mental
      health-related variables in relationship with paediatric TBI. Altogether, 15
      variables were derived from the cohort data with ICD-10 F-codes being available
      for mental health diagnoses for all parents. Bivariate and multivariate analyses
      were carried out using inpatient and outpatient diagnoses of child TBI. RESULTS:
      Paternal disorders due to psychoactive substance use (F10-F19) was associated
      with an increased inpatient TBI (OR=1.51; CI=1.07 to 2.14). Mood disorders (F30
      F39) were associated with higher rates of outpatient TBI (OR=1.42; CI=1.06 to
      1.90). Paternal personality and behavioural disorders (F60-F69) were linked with
      a twofold increase in risk across both categories of child TBI (OR=2.35; CI=1.41
      to 3.90) and (OR=2.29; CI=1.45 to 3.61), respectively. Among the maternal mental
      health factors associated with child TBI, schizophrenia and other non-mood
      psychotic disorders (F20-F29) were associated with an increase in inpatient
      traumatic brain injuries (iTBI) (OR=1.78; 1.22 to 2.59). Mothers having mood
      disorders (F30-F39) were more likely to have had a child who experienced an iTBI
      (OR=1.64; CI=1.20 to 2.22). Mothers with personality and behavioural disorders
      (F60-F69) were also found to have had children with an increased risk for iTBI
      (OR=2.30; CI=1.14 to 3.65). CONCLUSION: Taken together, these data should call
      attention to methods and strategies designed to augment and support caregiving
      environments with modalities that can foster mutually supportive households in
      cooperation with parents who have been diagnosed with a mental disorder.

PMID- 29363589
TI  - Tackling in physical education rugby: an unnecessary risk?

PMID- 29363590
TI  - Exercise programmes to prevent falls among older adults: modelling health gain,
      cost-utility and equity impacts.
AB  - BACKGROUND: Some falls prevention interventions for the older population appear
      cost-effective, but there is uncertainty about others. Therefore, we aimed to
      model three types of exercise programme each running for 25 years among 65+ year
      olds: (i) a peer-led group-based one; (ii) a home-based one and (iii) a
      commercial one. METHODS: An established Markov model for studying falls
      prevention in New Zealand (NZ) was adapted to estimate incremental cost
      effectiveness ratios (ICERs) in cost per quality-adjusted life-years (QALYs)
      gained. Detailed NZ experimental, epidemiological and cost data were used for the
      base year 2011. A health system perspective was taken and a discount rate of 3%
      applied. Intervention effectiveness estimates came from a Cochrane Review.
      RESULTS: The intervention generating the greatest health gain and costing the
      least was the home-based exercise programme intervention. Lifetime health gains
      were estimated at 47 100 QALYs (95%uncertainty interval (UI) 22 300 to 74 400).
      Cost-effectiveness was high (ICER: US$4640 per QALY gained; (95% UI US$996 to 10
      500)), and probably more so than a home safety assessment and modification
      intervention using the same basic model (ICER: US$6060). The peer-led group-based
      exercise programme was estimated to generate 42 000 QALYs with an ICER of
      US$9490. The commercially provided group programme was more expensive and less
      cost-effective (ICER: US$34 500). Further analyses by sex, age group and
      ethnicity (Indigenous Maori and non-Maori) for the peer-led group-intervention
      showed similar health gains and cost-effectiveness. CONCLUSIONS: Implementing any
      of these three types of exercise programme for falls prevention in older people
      could produce considerable health gain, but with the home-based version being
      likely to be the most cost-effective.

PMID- 29363592
TI  - Pebbled makes ripples: A transcription factor primes glutamatergic but not
      cholinergic neurons for degeneration.

PMID- 29363593
TI  - STAC proteins associate to the IQ domain of CaV1.2 and inhibit calcium-dependent
      inactivation.
AB  - The adaptor proteins STAC1, STAC2, and STAC3 represent a newly identified family
      of regulators of voltage-gated calcium channel (CaV) trafficking and function.
      The skeletal muscle isoform STAC3 is essential for excitation-contraction
      coupling and its mutation causes severe muscle disease. Recently, two distinct
      molecular domains in STAC3 were identified, necessary for its functional
      interaction with CaV1.1: the C1 domain, which recruits STAC proteins to the
      calcium channel complex in skeletal muscle triads, and the SH3-1 domain, involved
      in excitation-contraction coupling. These interaction sites are conserved in the
      three STAC proteins. However, the molecular domain in CaV1 channels interacting
      with the STAC C1 domain and the possible role of this interaction in neuronal
      CaV1 channels remained unknown. Using CaV1.2/2.1 chimeras expressed in dysgenic
      (CaV1.1-/-) myotubes, we identified the amino acids 1,641-1,668 in the C terminus
      of CaV1.2 as necessary for association of STAC proteins. This sequence contains
      the IQ domain and alanine mutagenesis revealed that the amino acids important for
      STAC association overlap with those making contacts with the C-lobe of calcium
      calmodulin (Ca/CaM) and mediating calcium-dependent inactivation of CaV1.2.
      Indeed, patch-clamp analysis demonstrated that coexpression of either one of the
      three STAC proteins with CaV1.2 opposed calcium-dependent inactivation, although
      to different degrees, and that substitution of the CaV1.2 IQ domain with that of
      CaV2.1, which does not interact with STAC, abolished this effect. These results
      suggest that STAC proteins associate with the CaV1.2 C terminus at the IQ domain
      and thus inhibit calcium-dependent feedback regulation of CaV1.2 currents.

PMID- 29363594
TI  - A virus-targeted plant receptor-like kinase promotes cell-to-cell spread of RNAi.
AB  - RNA interference (RNAi) in plants can move from cell to cell, allowing for
      systemic spread of an antiviral immune response. How this cell-to-cell spread of
      silencing is regulated is currently unknown. Here, we describe that the C4
      protein from Tomato yellow leaf curl virus can inhibit the intercellular spread
      of RNAi. Using this viral protein as a probe, we have identified the receptor
      like kinase (RLK) BARELY ANY MERISTEM 1 (BAM1) as a positive regulator of the
      cell-to-cell movement of RNAi, and determined that BAM1 and its closest homolog,
      BAM2, play a redundant role in this process. C4 interacts with the intracellular
      domain of BAM1 and BAM2 at the plasma membrane and plasmodesmata, the cytoplasmic
      connections between plant cells, interfering with the function of these RLKs in
      the cell-to-cell spread of RNAi. Our results identify BAM1 as an element required
      for the cell-to-cell spread of RNAi and highlight that signaling components have
      been coopted to play multiple functions in plants.

PMID- 29363591
TI  - Topoisomerases as anticancer targets.
AB  - Many cancer type-specific anticancer agents have been developed and significant
      advances have been made toward precision medicine in cancer treatment. However,
      traditional or nonspecific anticancer drugs are still important for the treatment
      of many cancer patients whose cancers either do not respond to or have developed
      resistance to cancer-specific anticancer agents. DNA topoisomerases, especially
      type IIA topoisomerases, are proved therapeutic targets of anticancer and
      antibacterial drugs. Clinically successful topoisomerase-targeting anticancer
      drugs act through topoisomerase poisoning, which leads to replication fork arrest
      and double-strand break formation. Unfortunately, this unique mode of action is
      associated with the development of secondary cancers and cardiotoxicity.
      Structures of topoisomerase-drug-DNA ternary complexes have revealed the exact
      binding sites and mechanisms of topoisomerase poisons. Recent advances in the
      field have suggested a possibility of designing isoform-specific human
      topoisomerase II poisons, which may be developed as safer anticancer drugs. It
      may also be possible to design catalytic inhibitors of topoisomerases by
      targeting certain inactive conformations of these enzymes. Furthermore,
      identification of various new bacterial topoisomerase inhibitors and regulatory
      proteins may inspire the discovery of novel human topoisomerase inhibitors. Thus,
      topoisomerases remain as important therapeutic targets of anticancer agents.

PMID- 29363595
TI  - Basal forebrain contributes to default mode network regulation.
AB  - The default mode network (DMN) is a collection of cortical brain regions that is
      active during states of rest or quiet wakefulness in humans and other mammalian
      species. A pertinent characteristic of the DMN is a suppression of local field
      potential gamma activity during cognitive task performance as well as during
      engagement with external sensory stimuli. Conversely, gamma activity is elevated
      in the DMN during rest. Here, we document that the rat basal forebrain (BF)
      exhibits the same pattern of responses, namely pronounced gamma oscillations
      during quiet wakefulness in the home cage and suppression of this activity during
      active exploration of an unfamiliar environment. We show that gamma oscillations
      are localized to the BF and that gamma-band activity in the BF has a directional
      influence on a hub of the rat DMN, the anterior cingulate cortex, during DMN
      dominated brain states. The BF is well known as an ascending, activating,
      neuromodulatory system involved in wake-sleep regulation, memory formation, and
      regulation of sensory information processing. Our findings suggest a hitherto
      undocumented role of the BF as a subcortical node of the DMN, which we speculate
      may be important for switching between internally and externally directed brain
      states. We discuss potential BF projection circuits that could underlie its role
      in DMN regulation and highlight that certain BF nuclei may provide potential
      target regions for up- or down-regulation of DMN activity that might prove useful
      for treatment of DMN dysfunction in conditions such as epilepsy or major
      depressive disorder.

PMID- 29363596
TI  - Nitrate modulates stem cell dynamics in Arabidopsis shoot meristems through
      cytokinins.
AB  - The shoot apical meristem (SAM) is responsible for the generation of all the
      aerial parts of plants. Given its critical role, dynamical changes in SAM
      activity should play a central role in the adaptation of plant architecture to
      the environment. Using quantitative microscopy, grafting experiments, and genetic
      perturbations, we connect the plant environment to the SAM by describing the
      molecular mechanism by which cytokinins signal the level of nutrient availability
      to the SAM. We show that a systemic signal of cytokinin precursors mediates the
      adaptation of SAM size and organogenesis rate to the availability of mineral
      nutrients by modulating the expression of WUSCHEL, a key regulator of stem cell
      homeostasis. In time-lapse experiments, we further show that this mechanism
      allows meristems to adapt to rapid changes in nitrate concentration, and thereby
      modulate their rate of organ production to the availability of mineral nutrients
      within a few days. Our work sheds light on the role of the stem cell regulatory
      network by showing that it not only maintains meristem homeostasis but also
      allows plants to adapt to rapid changes in the environment.

PMID- 29363597
TI  - Ephemeral connections for reaching and grasping.

PMID- 29363598
TI  - Focal versus distributed temporal cortex activity for speech sound category
      assignment.
AB  - Percepts and words can be decoded from distributed neural activity measures.
      However, the existence of widespread representations might conflict with the more
      classical notions of hierarchical processing and efficient coding, which are
      especially relevant in speech processing. Using fMRI and magnetoencephalography
      during syllable identification, we show that sensory and decisional activity
      colocalize to a restricted part of the posterior superior temporal gyrus (pSTG).
      Next, using intracortical recordings, we demonstrate that early and focal neural
      activity in this region distinguishes correct from incorrect decisions and can be
      machine-decoded to classify syllables. Crucially, significant machine decoding
      was possible from neuronal activity sampled across different regions of the
      temporal and frontal lobes, despite weak or absent sensory or decision-related
      responses. These findings show that speech-sound categorization relies on an
      efficient readout of focal pSTG neural activity, while more distributed activity
      patterns, although classifiable by machine learning, instead reflect collateral
      processes of sensory perception and decision.

PMID- 29363599
TI  - Human bone perivascular niche-on-a-chip for studying metastatic colonization.
AB  - Eight out of 10 breast cancer patients die within 5 years after the primary tumor
      has spread to the bones. Tumor cells disseminated from the breast roam the
      vasculature, colonizing perivascular niches around blood capillaries. Slow flows
      support the niche maintenance by driving the oxygen, nutrients, and signaling
      factors from the blood into the interstitial tissue, while extracellular matrix,
      endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here,
      we show the feasibility of developing a perfused bone perivascular niche-on-a
      chip to investigate the progression and drug resistance of breast cancer cells
      colonizing the bone. The model is a functional human triculture with stable
      vascular networks within a 3D native bone matrix cultured on a microfluidic chip.
      Providing the niche-on-a-chip with controlled flow velocities, shear stresses,
      and oxygen gradients, we established a long-lasting, self-assembled vascular
      network without supplementation of angiogenic factors. We further show that human
      bone marrow-derived mesenchymal stem cells, which have undergone phenotypical
      transition toward perivascular cell lineages, support the formation of capillary
      like structures lining the vascular lumen. Finally, breast cancer cells exposed
      to interstitial flow within the bone perivascular niche-on-a-chip persist in a
      slow-proliferative state associated with increased drug resistance. We propose
      that the bone perivascular niche-on-a-chip with interstitial flow promotes the
      formation of stable vasculature and mediates cancer cell colonization.

PMID- 29363600
TI  - Abrupt change of the superconducting gap structure at the nematic critical point
      in FeSe1-xSx.
AB  - The emergence of the nematic electronic state that breaks rotational symmetry is
      one of the most fascinating properties of the iron-based superconductors, and has
      relevance to cuprates as well. FeSe has a unique ground state in which
      superconductivity coexists with a nematic order without long-range magnetic
      ordering, providing a significant opportunity to investigate the role of
      nematicity in the superconducting pairing interaction. Here, to reveal how the
      superconducting gap evolves with nematicity, we measure the thermal conductivity
      and specific heat of FeSe1 - x S x , in which the nematicity is suppressed by
      isoelectronic sulfur substitution and a nematic critical point (NCP) appears at
      [Formula: see text] We find that, in the whole nematic regime ([Formula: see
      text]), the field dependence of two quantities consistently shows two-gap
      behavior; one gap is small but highly anisotropic with deep minima or line nodes,
      and the other is larger and more isotropic. In stark contrast, in the tetragonal
      regime ([Formula: see text]), the larger gap becomes strongly anisotropic,
      demonstrating an abrupt change in the superconducting gap structure at the NCP.
      Near the NCP, charge fluctuations of [Formula: see text] and [Formula: see text]
      orbitals are enhanced equally in the tetragonal side, whereas they develop
      differently in the orthorhombic side. Our observation therefore directly implies
      that the orbital-dependent nature of the nematic fluctuations has a strong impact
      on the superconducting gap structure and hence on the pairing interaction.

PMID- 29363601
TI  - Hunter-gatherer populations inform modern ecology.

PMID- 29363602
TI  - Evolution of vertical and oblique transmission under fluctuating selection.
AB  - The evolution and maintenance of social learning, in competition with individual
      learning, under fluctuating selection have been well-studied in the theory of
      cultural evolution. Here, we study competition between vertical and oblique
      cultural transmission of a dichotomous phenotype under constant, periodically
      cycling, and randomly fluctuating selection. Conditions are derived for the
      existence of a stable polymorphism in a periodically cycling selection regime.
      Under such a selection regime, the fate of a genetic modifier of the rate of
      vertical transmission depends on the length of the cycle and the strength of
      selection. In general, the evolutionarily stable rate of vertical transmission
      differs markedly from the rate that maximizes the geometric mean fitness of the
      population. The evolution of rules of transmission has dramatically different
      dynamics from the more frequently studied modifiers of recombination, mutation,
      or migration.

PMID- 29363604
TI  - Reply to Safra et al.: Lack of theoretical rationale and selective analysis does
      not imply no strong evidence.

PMID- 29363605
TI  - No strong evidence that authoritarian attitudes are driven by a lack of control.

PMID- 29363603
TI  - The eardrums move when the eyes move: A multisensory effect on the mechanics of
      hearing.
AB  - Interactions between sensory pathways such as the visual and auditory systems are
      known to occur in the brain, but where they first occur is uncertain. Here, we
      show a multimodal interaction evident at the eardrum. Ear canal microphone
      measurements in humans (n = 19 ears in 16 subjects) and monkeys (n = 5 ears in
      three subjects) performing a saccadic eye movement task to visual targets
      indicated that the eardrum moves in conjunction with the eye movement. The
      eardrum motion was oscillatory and began as early as 10 ms before saccade onset
      in humans or with saccade onset in monkeys. These eardrum movements, which we dub
      eye movement-related eardrum oscillations (EMREOs), occurred in the absence of a
      sound stimulus. The amplitude and phase of the EMREOs depended on the direction
      and horizontal amplitude of the saccade. They lasted throughout the saccade and
      well into subsequent periods of steady fixation. We discuss the possibility that
      the mechanisms underlying EMREOs create eye movement-related binaural cues that
      may aid the brain in evaluating the relationship between visual and auditory
      stimulus locations as the eyes move.

PMID- 29363606
TI  - Reply to Lund: Where does the gravitostat fit in?

PMID- 29363607
TI  - Weighing the evidence for a body mass-regulating gravitostat.

PMID- 29363608
TI  - Implementation of a colour-coded universal protocol safety initiative in
      Guatemala.
AB  - BACKGROUND: Universal protocol implementation can be challenging in low-income or
      middle-income countries, particularly when providers work together across
      language barriers. The aim of this quality improvement initiative was to test the
      implementation of a colour-coded universal protocol in a Guatemalan hospital
      staffed by US and Guatemalan providers. METHODS: From 2013 to 2016, a US and
      Guatemalan team implemented a universal protocol at a Guatemalan surgical centre
      for children undergoing general surgical or urologic procedures. The protocol was
      a two-step patient identification and documentation checklist, with the first
      step of all chart element verification in the preoperative area, after which a
      blue hat was placed on the patient as a visual cue that this was completed. The
      second step included checklist confirmation in the operating room prior to the
      procedure. We tested protocol implementation over three phases, identifying
      implementation barriers and modifying clinical workflow after each phase. We
      measured the error rate in documentation or other universal protocol steps at
      each phase and made modifications based on iterative analysis. RESULTS: Over the
      course of programme implementation, we substantially decreased the rate of errors
      in documentation or other universal protocol elements. After the first phase,
      30/51 patients (58.8%) had at least one error. By the third phase, only 2/43
      patients (4.6%) had any errors. All errors were corrected prior to surgery with
      no adverse outcomes. CONCLUSIONS: Care teams of providers from different
      countries pose potential challenges with patient safety. Implementation of a
      colour-coded universal protocol in this setting can prevent and reduce errors
      that could potentially lead to patient harm.

PMID- 29363609
TI  - Flavour capsule cigarette use among US adult cigarette smokers.
AB  - INTRODUCTION: Flavour capsule cigarettes are a recent product worldwide, and
      little is known about the epidemiology of their use. We used data from a
      nationally representative survey to understand the sociodemographic
      characteristics of flavour capsule cigarette smokers and reasons for flavour
      capsule use. METHODS: Data were from the nationally representative, U.S.
      Population Assessment of Tobacco and Health survey (2013-2014). Analyses included
      7181 adults, aged 18-44 years, who were current or former established (>=100
      lifetime cigarettes) cigarette smokers. Participants reported their usual brand
      of cigarettes which were classified as non-menthol, menthol or flavour capsule.
      Analyses assessed differences in participant demographics, smoking patterns and
      reasons for use by product type among those aged 18-24 years. Analyses were
      weighted to account for the survey design. RESULTS: Flavour capsule cigarettes
      were the usual cigarettes among 9.4% of smokers aged 18-24 years and 6.0%, 3.7%
      and <1% of smokers aged 25-34, 35-44 and >=45 years, respectively. Among smokers
      aged 18-24 year, a significantly higher percentage of Hispanic smokers (17.3%)
      usually used flavour capsule cigarettes versus non-Hispanic white (8.4%, P<0.05)
      and non-Hispanic black (3.2%, P<0.05) smokers. Flavour capsule use was associated
      with later onset of smoking and lower levels of nicotine dependency and flavour
      capsule users placed more emphasis on taste, lower price and pack design than
      menthol or non-menthol users. CONCLUSIONS: Flavour capsule cigarettes use is
      highest in young adults, particularly Hispanics. Young adult predominance, lower
      level of addiction symptoms and emphasis on pack design by flavour capsule users
      suggest that these products may be positioned as starter products.

PMID- 29363610
TI  - Public misperception that very low nicotine cigarettes are less carcinogenic.
AB  - OBJECTIVE: The USA is considering a very low nicotine content (VLNC) cigarette
      standard. We sought to characterise the prevalence and correlates of the
      incorrect belief that VLNC cigarettes are less carcinogenic than current
      cigarettes, as this could reduce motivation to quit. METHODS: Participants were a
      nationally representative sample of 650 adult smokers in the USA. In 2015-2016,
      before the VLNC proposal became public, these smokers took part in an online
      survey. We used multivariate weighted analyses to calculate ORs and percentages
      and a chi2 test to examine the association between variables. RESULTS: Overall,
      47.1% of smokers believed that smoking VLNC cigarettes for 30 years would be less
      likely to cause cancer than smoking current cigarettes. This misperception was
      more common among smokers who were aged above 55 (56.6%) and black (57.4%).
      Additionally, 23.9% of smokers reported they would be less likely to quit if the
      USA adopted a VLNC standard. Thinking that VLNC cigarettes would be less
      carcinogenic was associated with smokers reporting they would be less likely to
      quit (P<0.01). CONCLUSIONS: Many smokers had the misperception that smoking VLNC
      cigarettes is less likely to cause cancer, and some stated that they would be
      less likely to quit. A VLNC standard may be more effective if accompanied by a
      communication campaign that emphasises the continued dangers of smoking VLNC
      cigarettes due to the many toxic chemicals in smoke.

PMID- 29363611
TI  - Price elasticity of demand of non-cigarette tobacco products: a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To systematically review the price elasticity of demand of non
      cigarette tobacco products. DATA SOURCES: Medline, Embase, EconLit and the Web of
      Science without language or time restrictions. STUDY SELECTION: Two reviewers
      screened title and abstracts, then full texts, independently and in duplicate. We
      based eligibility criteria on study design (interventional or observational),
      population (individuals or communities without geographic restrictions),
      intervention (price change) and outcome (change in demand). DATA EXTRACTION: We
      abstracted data on study features, outcome measures, statistical approach, and
      single best own- and cross-price elasticity estimates with respect to cigarettes.
      We conducted a random effects meta-analysis for estimates of similar product,
      outcome and country income level. For other studies we reported median
      elasticities by product and country income level. DATA SYNTHESIS: We analysed 36
      studies from 15 countries yielding 125 elasticity estimates. A 10% price increase
      would reduce demand by: 8.3% for cigars (95% CI 2.9 to 13.8), 6.4% for roll your
      owns (95% CI 4.3 to 8.4), 5.7% for bidis (95% CI 4.3 to 7.1) and 2.1% for
      smokeless tobacco (95% CI -0.6 to 4.8). Median price elasticities for all ten
      products were also negative. Results from few studies that examined cross-price
      elasticity suggested a positive substitution effect between cigarette and non
      cigarette tobacco products. CONCLUSIONS: There is sufficient evidence in support
      of the effectiveness of price increases to reduce consumption of non-cigarette
      tobacco products as it is for cigarettes. Positive substitutability between
      cigarette and non-cigarette tobacco products suggest that tax and price increases
      need to be simultaneous and comparable across all tobacco products.

PMID- 29363614
TI  - Science and Culture: Painting with invasive pigments.

PMID- 29363612
TI  - Spatial Tissue Proteomics Quantifies Inter- and Intratumor Heterogeneity in
      Hepatocellular Carcinoma (HCC).
AB  - The interpatient variability of tumor proteomes has been investigated on a large
      scale but many tumors display also intratumoral heterogeneity regarding
      morphological and genetic features. It remains largely unknown to what extent the
      local proteome of tumors intrinsically differs. Here, we used hepatocellular
      carcinoma as a model system to quantify both inter- and intratumor heterogeneity
      across human patient specimens with spatial resolution. We defined proteomic
      features that distinguish neoplastic from the directly adjacent nonneoplastic
      tissue, such as decreased abundance of NADH dehydrogenase complex I. We then
      demonstrated the existence of intratumoral variations in protein abundance that
      re-occur across different patient samples, and affect clinically relevant
      proteins, even in the absence of obvious morphological differences or genetic
      alterations. Our work demonstrates the suitability and the benefits of using mass
      spectrometry-based proteomics to analyze diagnostic tumor specimens with spatial
      resolution. Data are available via ProteomeXchange with identifier PXD007052.

PMID- 29363616
TI  - Novel magnetic-fluorescent bifunctional Janus nanofiber membrane.
AB  - Magnetic-fluorescent bifunctional materials have received global attention owing
      to their potential in many fields. Herein, we reported a novel magnetic
      fluorescent bifunctional Janus nanofiber membrane (NFM) by adding the as-prepared
      magnetic CoFe2O4 nanoparticles into the polyacrylonitrile (PAN) side (m-PAN) and
      the fluorescent molecules of 1,8-naphthalene anhydride (1,8-NAD) into the
      polyvinylpyrrolidone (PVP) side (f-PVP) via electrospinning method. The obtained
      m-PAN/f-PVP Janus NFM exhibited excellent magnetic performance and high
      fluorescent properties due to the unique structure. Compared with the m-PAN/f-PVP
      composite NFM, the Janus NFM showed higher fluorescent performance because the
      fluorescent molecules were isolated from the magnetic nanoparticles. In addition,
      the Janus NFM not only maintain the good self-supporting state in water but also
      realize a directional movement attracted by a magnet. The unique structure of
      Janus nanofiber is of great importance and demonstrates great potential
      applications.

PMID- 29363613
TI  - Effect of increasing the price of sugar-sweetened beverages on alcoholic beverage
      purchases: an economic analysis of sales data.
AB  - BACKGROUND: Taxing soft-drinks may reduce their purchase, but assessing the
      impact on health demands wider consideration on alternative beverage choices.
      Effects on alcoholic drinks are of particular concern, as many contain similar or
      greater amounts of sugar than soft-drinks and have additional health harms.
      Changes in consumption of alcoholic drinks may reinforce or negate the intended
      effect of price changes for soft-drinks. METHODS: A partial demand model, adapted
      from the Almost Ideal Demand System, was applied to Kantar Worldpanel data from
      31 919 households from January 2012 to December 2013, covering drink purchases
      for home consumption, providing ~6 million purchases aggregated into 11 groups,
      including three levels of soft-drink, three of other non-alcoholic drinks and
      five of alcoholic drinks. RESULTS: An increase in the price of high-sugar drinks
      leads to an increase in the purchase of lager, an increase in the price of medium
      sugar drinks reduces purchases of alcoholic drinks, while an increase in the
      price of diet/low-sugar drinks increases purchases of beer, cider and wines.
      Overall, the effects of price rises are greatest in the low-income group.
      CONCLUSION: Increasing the price of soft-drinks may change purchase patterns for
      alcohol. Increasing the price of medium-sugar drinks has the potential to have a
      multiplier-effect beneficial to health through reducing alcohol purchases, with
      the converse for increases in the price of diet-drinks. Although the reasons for
      such associations cannot be explained from this analysis, requiring further
      study, the design of fiscal interventions should now consider these wider
      potential outcomes.

PMID- 29363617
TI  - A fast dual wavelength laser beam fluid-less optical CT scanner for radiotherapy
      3D gel dosimetry I: design and development.
AB  - Three dimensional dosimetry by optical CT readout of radiosensitive gels or
      solids has previously been indicated as a solution for measurement of
      radiotherapy 3D dose distributions. The clinical uptake of these dosimetry
      methods has been limited, partly due to impracticalities of the optical readout
      such as the expertise and labour required for refractive index fluid matching. In
      this work a fast laser beam optical CT scanner is described, featuring fluid-less
      and dual wavelength operation. A second laser with a different wavelength is used
      to provide an alternative reference scan to the commonly used pre-irradiation
      scan. Transmission data for both wavelengths is effectively acquired
      simultaneously, giving a single scan process. Together with the elimination of
      refractive index fluid matching issues, scanning practicality is substantially
      improved. Image quality and quantitative accuracy were assessed for both dual and
      single wavelength methods. The dual wavelength scan technique gave improvements
      in uniformity of reconstructed optical attenuation coefficients in the sample 3D
      volume. This was due to a reduction of artefacts caused by scan to scan changes.
      Optical attenuation measurement accuracy was similar for both dual and single
      wavelength modes of operation. These results established the basis for further
      work on dosimetric performance.

PMID- 29363618
TI  - Towards miniaturized closed-loop optogenetic stimulation devices.
AB  - OBJECTIVE: Electrical brain stimulation provides therapeutic benefits for
      patients with drug-resistant neurological disorders. It, however, has restricted
      access to cell-type selectivity which limits its treatment effectiveness.
      Optogenetics, in contrast, enables precise targeting of a specific cell type
      which can address the issue with electrical brain stimulation. It, nonetheless,
      disregards real-time brain responses in delivering optimized stimulation to
      target cells. Closed-loop optogenetics, on the other hand, senses the difference
      between normal and abnormal states of the brain, and modulates stimulation
      parameters to achieve the desired stimulation outcome. Current review articles on
      closed-loop optogenetics have focused on its theoretical aspects and potential
      benefits. A review of the recent progress in miniaturized closed-loop optogenetic
      stimulation devices is thus needed. APPROACH: This paper presents a comprehensive
      study on the existing miniaturized closed-loop optogenetic stimulation devices
      and their internal components. MAIN RESULTS: Hardware components of closed-loop
      optogenetic stimulation devices including electrode, light-guiding mechanism,
      optical source, neural recorder, and optical stimulator are discussed. Next,
      software modules of closed-loop optogenetic stimulation devices including feature
      extraction, classification, control, and stimulation parameter modulation are
      described. Then, the existing devices are categorized into open-loop and closed
      loop groups, and the combined operation of their neural recorder, optical
      stimulator, and control approach is discussed. Finally, the challenges in the
      design and implementation of closed-loop optogenetic stimulation devices are
      presented, suggestions on how to tackle these challenges are given, and future
      directions for closed-loop optogenetics are stated. SIGNIFICANCE: A generic
      architecture for closed-loop optogenetic stimulation devices involving both
      hardware and software perspectives is devised. A comprehensive investigation into
      the most current miniaturized and tetherless closed-loop optogenetic stimulation
      devices is given. A detailed comparison of the closed-loop optogenetic
      stimulation devices is presented.

PMID- 29363619
TI  - A fast dual wavelength laser beam fluid-less optical CT scanner for radiotherapy
      3D gel dosimetry II: dosimetric performance.
AB  - New clinical radiotherapy dosimetry systems need comprehensive demonstration of
      measurement quality. Practicality and reliability are other important aspects for
      clinical dosimeters. In this work the performance of an optical CT scanner for
      true 3D dosimetry is assessed using a radiochromic gel dosimeter. The fluid-less
      scanner utilised dual lasers to avoid the necessity for pre-irradiation scans and
      give greater robustness of image quality, enhancing practicality. Calibration
      methods using both cuvettes and reconstructed volumes were developed. Dosimetric
      accuracy was similar for dual and single wavelength measurements, except that
      cuvette calibration reliability was reduced for dual wavelength without pre
      irradiation scanning. Detailed performance parameters were specified for the
      dosimetry system indicating the suitability for clinical use. The most
      significant limitations of the system were due to the gel dosimeter rather than
      the optical CT scanner. Quality assurance guidelines were developed to maintain
      dosimetry system performance in routine use.

PMID- 29363620
TI  - Biopolymer-based membranes associated with osteogenic growth peptide for guided
      bone regeneration.
AB  - Barrier membranes for guided bone regeneration (GBR) mainly promote mechanical
      maintenance of bone defect space and induce osteopromotion. Additionally,
      biopolymer-based membranes may provide greater bioactivity and biocompatibility
      due to their similarity to extracellular matrix (ECM). In this study, biopolymers
      based membranes from bacterial cellulose (BC) and collagen (COL) associated with
      osteogenic growth peptide (OGP(10-14)) were evaluated to determine in vitro
      osteoinductive potential in early osteogenesis; moreover, histological study was
      performed to evaluate the BC-COL OGP(10-14) membranes on bone healing after GBR
      in noncritical defects in rat femur. The results showed that the BC-COL and BC
      COL OGP(10-14) membranes promoted cell proliferation and alkaline phosphatase
      activity in osteoblastic cell cultures. However, ECM mineralization was similar
      between cultures grown on BC OGP(10-14) and BC-COL OGP(10-14) membranes. In vivo
      results showed that all the membranes tested, including the peptide-free BC
      membrane, promoted better bone regeneration than control group. Furthermore, the
      BC-COL OGP(10-14) membranes induced higher radiographic density in the repaired
      bone than the other groups at 1, 4 and 16 weeks. Histomorphometric analyses
      revealed that the BC-COL OGP(10-14) induced higher percentage of bone tissue in
      the repaired area at 2 and 4 weeks than others membranes. In general, these
      biopolymer-based membranes might be potential candidates for bone regeneration
      applications.

PMID- 29363621
TI  - The fabrication of highly conductive and flexible Ag pattern through baking Ag
      nanospheres - nanoplates hybrid ink at a low temperature of 100 degrees C.
AB  - With the aim of developing highly conductive ink for flexible electronics on heat
      sensitive substrates, Ag nanospheres and nanoplates were mixed to synthesize
      hybrid inks. Five kinds of hybrid ink and two types of pure ink were written to
      square shape on Epson photo paper using rollerball pens and sintered at a low
      temperature (100C). The microstructure, electrical resistivity, surface porosity,
      hardness and flexibility of silver patterns were systematically investigated and
      compared. It was observed that the optimal mixing ratio of nanospheres and
      nanoplates was 1:1, which equipped the directly written pattern with excellent
      electrical and mechanical properties. The electrical resistivity was 0.103
      MUOmega.m, which was only 6.5 times of bulk silver. The enhancement compared to
      pure silver nanospheres or nanoplates based ink was owing to the combined action
      of nanospheres and nanoplates. It was a valued way to prepare Ag nanoink with
      good performance for printed/written electronics.

PMID- 29363622
TI  - Modified cable equation incorporating transverse polarization of neuronal
      membranes for accurate coupling of electric fields.
AB  - OBJECTIVE: We present a theory and computational methods to incorporate
      transverse polarization of neuronal membranes into the cable equation to account
      for the secondary electric field generated by the membrane in response to
      transverse electric fields. The effect of transverse polarization on nonlinear
      neuronal activation thresholds is quantified and discussed in the context of
      previous studies using linear membrane models. APPROACH: The response of neuronal
      membranes to applied electric fields is derived under two time scales and a
      unified solution of transverse polarization is given for spherical and
      cylindrical cell geometries. The solution is incorporated into the cable equation
      re-derived using an asymptotic model that separates the longitudinal and
      transverse dimensions. Two numerical methods are proposed to implement the
      modified cable equation. Several common neural stimulation scenarios are tested
      using two nonlinear membrane models to compare thresholds of the conventional and
      modified cable equations. MAIN RESULTS: The implementations of the modified cable
      equation incorporating transverse polarization are validated against previous
      results in the literature. The test cases show that transverse polarization has
      limited effect on activation thresholds. The transverse field only affects
      thresholds of unmyelinated axons for short pulses and in low-gradient field
      distributions, whereas myelinated axons are mostly unaffected. SIGNIFICANCE: The
      modified cable equation captures the membrane's behavior on different time scales
      and models more accurately the coupling between electric fields and neurons. It
      addresses the limitations of the conventional cable equation and allows sound
      theoretical interpretations. The implementation provides simple methods that are
      compatible with current simulation approaches to study the effect of transverse
      polarization on nonlinear membranes. The minimal influence by transverse
      polarization on axonal activation thresholds for the nonlinear membrane models
      indicates that predictions of stronger effects in linear membrane models with a
      fixed activation threshold are inaccurate. Thus, the conventional cable equation
      works well for most neuroengineering applications, and the presented modeling
      approach is well suited to address the exceptions.

PMID- 29363623
TI  - A low-cost microwell device for high-resolution imaging of neurite outgrowth in
      3D.
AB  - OBJECTIVE: Current neuronal cell culture is mostly performed on two-dimensional
      (2D) surfaces, which lack many of the important features of the native
      environment of neurons, including topographical cues, deformable extracellular
      matrix, and spatial isotropy or anisotropy in three dimensions. Although three
      dimensional (3D) cell culture systems provide a more physiologically relevant
      environment than 2D systems, their popularity is greatly hampered by the lack of
      easy-to-make-and-use devices. We aim to develop a widely applicable 3D culture
      procedure to facilitate the transition of neuronal cultures from 2D to 3D.
      APPROACH: We made a simple microwell device for 3D neuronal cell culture that is
      inexpensive, easy to assemble, and fully compatible with commonly used imaging
      techniques, including super-resolution microscopy. MAIN RESULTS: We developed a
      novel gel mixture to support 3D neurite regeneration of Aplysia bag cell neurons,
      a system that has been extensively used for quantitative analysis of growth cone
      dynamics in 2D. We found that the morphology and growth pattern of bag cell
      growth cones in 3D culture closely resemble the ones of growth cones observed in
      vivo. We demonstrated the capability of our device for high-resolution imaging of
      cytoskeletal and signaling proteins as well as organelles. SIGNIFICANCE: Neuronal
      cell culture has been a valuable tool for neuroscientists to study the behavior
      of neurons in a controlled environment. Compared to 2D, neurons cultured in 3D
      retain the majority of their native characteristics, while offering higher
      accessibility, control, and repeatability. We expect that our microwell device
      will facilitate a wider adoption of 3D neuronal cultures to study the mechanisms
      of neurite regeneration.

PMID- 29363624
TI  - Improving carrier transport in Cu2O thin films by rapid thermal annealing.
AB  - Cuprous oxide (Cu2O) is a promising material for large scale photovoltaic
      applications. The efficiencies of thin film structures are, however, currently
      lower than those for structures based on Cu2O sheets, possibly due to their
      poorer transport properties. This study shows that post-deposition rapid thermal
      annealing (RTA) of Cu2O films is an effective approach for improving carrier
      transport in films prepared by reactive magnetron sputtering. The as-deposited
      Cu2O films were poly-crystalline, p-type, with weak near band edge (NBE) emission
      in photoluminescence spectra, a grain size of ~100 nm and a hole mobility of 2-18
      cm2 V-1 s-1. Subsequent RTA (3 min) at a pressure of 50 Pa and temperatures of
      600-1000  degrees C enhanced the NBE by 2-3 orders of magnitude, evidencing
      improved crystalline quality and reduction of non-radiative carrier
      recombination. Both grain size and hole mobility were increased considerably upon
      RTA, reaching values above 1 um and up to 58 cm2 V-1 s-1, respectively, for films
      annealed at 900-1000  degrees C. These films also exhibited a resistivity of ~50
      200 Omega cm, a hole concentration of ~1015 cm-3 at room temperature, and a
      transmittance above 80%.

PMID- 29363626
TI  - Response to topical halcinonide following fractional carbon dioxide laser
      pretreatment in a pretibial myxedema patient.

PMID- 29363625
TI  - Rapid calibration of an intracortical brain-computer interface for people with
      tetraplegia.
AB  - OBJECTIVE: Brain-computer interfaces (BCIs) can enable individuals with
      tetraplegia to communicate and control external devices. Though much progress has
      been made in improving the speed and robustness of neural control provided by
      intracortical BCIs, little research has been devoted to minimizing the amount of
      time spent on decoder calibration. APPROACH: We investigated the amount of time
      users needed to calibrate decoders and achieve performance saturation using two
      markedly different decoding algorithms: the steady-state Kalman filter, and a
      novel technique using Gaussian process regression (GP-DKF). MAIN RESULTS: Three
      people with tetraplegia gained rapid closed-loop neural cursor control and peak,
      plateaued decoder performance within 3 min of initializing calibration. We also
      show that a BCI-naive user (T5) was able to rapidly attain closed-loop neural
      cursor control with the GP-DKF using self-selected movement imagery on his first
      ever day of closed-loop BCI use, acquiring a target 37 s after initiating
      calibration. SIGNIFICANCE: These results demonstrate the potential for an
      intracortical BCI to be used immediately after deployment by people with
      paralysis, without the need for user learning or extensive system calibration.

PMID- 29363627
TI  - Primary cutaneous CD4 positive small/medium T cell lymphoma.

PMID- 29363628
TI  - Indications and outcome of tracheostomy in Ilorin, North Central Nigeria: 10
      years review.
AB  - BACKGROUND: The study aims to highlight common indications as well as outcome of
      treatment among patients with tracheostomy in Ilorin, North-Central Nigeria.
      METHODS: A review of clinical records of all patients with tracheostomy over a
      period of ten years (2002-2011), using the Theatre, Ward, ICU and the emergency
      register after approval from the ethical review committee. Data retrieved
      included; demographic profile, primary diagnosis, indication for tracheostomy,
      surgical technique, hospital admission and care outcome of management. All
      information retrieved input and analysed using an SPSS version 17.0 and data
      analyzed descriptively. RESULTS: Seventy-six patients had complete data for
      analysis, age range from 1-89yrs, and mean age of 41.9yrs. There are 48males and
      28 females with M:F ratio of 1.6:1. Majority of the patients were in the 3rd-5th
      decade. About 47.4% had temporary tracheostomy. The commonest indication for
      tracheostomy is upper airway obstruction secondary to aerodigestive tract tumors
      in 60.5%, then trauma in 26.3%. The complications are higher among the under
      tens'. Out of the 36 temporary tracheostomy only 18 were successfully
      decannulated. The mean hospital stay was 22+/-2days. Overall 15% mortality was
      recorded. CONCLUSION: Common reason for tracheostomy is essentially same earlier
      documentation in developing countries, common among males, emergency type still
      most common, neoplasm, prolonged intubation and trauma are the commonest
      indications, its complication is still high among the under tens'. The outcome is
      good with 15% mortality due to the primary disease and not from tracheostomy.

PMID- 29363629
TI  - The astigmatic effect of pterygium in a Tertiary Hospital in Kano, Nigeria.
AB  - AIM: This study aims to determine the effect of pterygium excision on the degree
      of corneal induced astigmatism and visual acuity. PATIENTS AND METHODS: This was
      a prospective interventional study conducted between September 2012 and June
      2013. Consecutive patients with pterygium who met the inclusion criteria were
      recruited into the study. They had a basic eye examination, and those with
      existing comorbidity were excluded. Selected patients had pterygium excision
      using the bare sclera technique with intraoperative application of Mitomycin C.
      Detailed pre- and post-operative evaluation and refraction was done. RESULTS:
      There were 45 eyes of 33 patients aged 28-75 years. The mean age was 56.12 +
      12.38 years. Six eyes had Grade I, 29 eyes had Grade II and 10 eyes had Grade III
      pterygium. The mean value for preoperative astigmatism was 2.12 +/- 1.09 diopter
      cylinder (DC) while that for postoperative astigmatism was 0.72 +/- 0.50 DC (P =
      0.000). Surgery was associated with statistically significant increase in
      postoperative visual acuity. (P = 0.000). CONCLUSION: This study has shown that
      the degree of pterygium-induced astigmatism reduces significantly following
      surgical excision. Pterygium excision was associated with improvement in visual
      acuity.

PMID- 29363630
TI  - Assessment of some indicators of oxidative stress in nigerian sickle cell anemic
      patients.
AB  - BACKGROUND: Oxidative stress, the imbalance between the productive of reactive
      species and antioxidant defences notably plays an important role in the
      pathogenesis of sickle cell disease. Generating the necessary data about
      oxidative stress in patients with sickle cell anemia (SCA) would help in
      developing cost-effective and accessible treatment interventions of SCA in
      resource-poor countries. AIM: The aim of this study is to evaluate the levels
      plasma lipid peroxidation product, malondialdehyde (MDA), serum nitric oxide
      (NO), and total antioxidant activity (TAOA) as indicators of oxidative stress in
      sickle cell individuals. MATERIALS AND METHODS: In this pilot study, 52 patients;
      homozygous (Hb SS) sickle cell patients confirmed by cellulose electrophoresis
      and 20 age- and sex-matched healthy (Hb AA) controls were subjected to analysis
      of NO, MDA, and TAOA. The plasma MDA was measured by a thiobarbituric reaction,
      (NO) was evaluated by the method described by Guevara et al. using Griess reagent
      and the TAOA of serum was determined by the method of Koracevic et al. RESULTS:
      The results showed a statistically significant decrease and increase in baseline
      levels of NO and MDA, respectively, in Hb SS group when compared with the control
      Hb AA (P = 0.000 and 95% confidence interval [CI] of 0.10-0.18 and -9.67--5.57,
      respectively). A slight decrease in the TAOA level between the groups was
      observed although not statistically significant (P = 0.15 95% CI was -0.28-2.90).
      CONCLUSION: The results showed of imbalance between oxidant and antioxidant
      status in patients with SCA. Antioxidant supplementation may be a cheap
      assessable intervention for in sickle cell individuals (in the steady state or in
      crisis) to prevent further oxidative damage to the erythrocytes.

PMID- 29363631
TI  - Human immunodeficiency virus seroprevalence in patients with invasive cervical
      cancer in Zaria, North-Western Nigeria.
AB  - BACKGROUND: Cervical cancer is the commonest gynecological malignancy in our
      environment and is an Acquired Immuno-Deficiency Syndrome (AIDS)-associated
      malignancy. Documented data on the Human Immune-deficiency Virus (HIV)
      seroprevalence among patients with cervical cancer in our environment are scarce.
      OBJECTIVE: The aim of this study is to determine the prevalence of HIV infection
      in women with cancer of the cervix. STUDY DESIGN: The work is a descriptive
      survey by design, concentrating in frequency of occurrences of prevalence of the
      dissease in either cases for a number of years retrospectively carried out at the
      Radiotherapy and Oncology Centre of Ahmadu Bello University Teaching Hospital
      (ABUTH) Zaria. SETTING: The study was carried out at the Radiotherapy and
      Oncology Centre of ABUTH, Zaria. MATERIALS AND METHODS: A 5 years retrospective
      review of patients with histologically-proven cancer of the cervix seen in the
      Radiotherapy and Oncology Centre, ABUTH, Zaria, North-Western Nigeria was
      undertaken. Data such as age, clinical stage of disease and HIV seropositivity at
      presentation were retrieved from the case files. Data analysis was done using the
      SPSS statistical package version IBM 23 and results presented in frequencies and
      percentages and charts for graphical presentation. RESULTS: A total of 1,639
      patients seen over a period of 5 years were reviewed. The age range of both
      groups of patients was from 28 years to 92 years with a mean age of 50.5 years.
      One thousand five hundred and seventy-three of the patients (96%) were
      seronegative to the HIV tests while 66 (4%) were seropositive. The age range of
      the seropositive patients was 28 - 49 years with a mean age of 38.1 years. Their
      peak age at presentation was 30 - 39 years. Similarly, the age range of the
      seronegative patients was 30 - 92 years with a peak at 40-49 years. 51 (89.5%) of
      the HIV seropositive patients presented with advanced clinical stage disease,
      i.e, International Federation of Obstetrics and Gynecology (FIGO) stage 2B and
      above. 1,363 (93%) of the HIV seronegative patients presented with FIGO 2B
      disease and above, both scenario illustrating the general trend of late
      presentation of cancer patients to hospital in our environment. CONCLUSION: The
      study shows that the prevalence of HIV infection among cervical cancer patients
      is low in Zaria, with earlier age of development of cervical cancer among HIV
      seropositive patients compared to HIV seronegative counterparts. Both group of
      patients present with cervical cancer at an advanced stage. More studies
      therefore needed to be done to identify the predisposing factors to the high
      incidence of invasive cervical cancer in our environment and introduction of
      cervical cancer screening at an earlier age among HIV seropositive patients.

PMID- 29363632
TI  - Current indications for extremity amputations in Maiduguri, North-East Nigeria: A
      6-year retrospective review.
AB  - OBJECTIVE: To know the the commonest cause for extremity amputation in UMTH in
      recent times, following the result of two previous studies citing malignancy and
      later trauma, at the University of Maiduguri Teaching Hospital, a tertiary
      hospital in North East Nigeria. METHOD: We retrieved folders of all patients who
      had extremity amputation from January 2010 to December 2016 in our center. There
      were one hundred and sixty three case notes, accounting for one hundred and sixty
      five amputations. RESULTS: Of the 165 amputations in 163 patients, 94 (57.0%)
      were as a result of this problem. It was also noted that the affected patients
      were regular with their medications, bringing into question the efficacy of these
      medications. Trauma however remains the second common cause for amputation,
      accounting for 22 (13.3%), followed by complications from splints of traditional
      bone setters (TBS) which accounted for 20 (12.2%). CONCLUSION: Complicated
      diabetes mellitus is the commonest cause oa amputations in recent times in our
      center.

PMID- 29363633
TI  - Prescribing pattern and antibiotic use for hospitalized children in a Northern
      Nigerian Teaching Hospital.
AB  - BACKGROUND: Assessment of patterns of drug to detect performance problems and
      compliance with standards facilitates objective comparisons and impact
      evaluation. Children are at higher risk of consequences of irrational prescribing
      and antibiotic misuse. OBJECTIVE: The objective of the study was to evaluate the
      prescribing pattern and utilization of antibiotics for children using standard
      prescribing indicators and indices of rational drug prescribing. MATERIALS AND
      METHODS: This was a retrospective study of prescriptions for pediatric inpatients
      at a teaching hospital in Northern Nigeria. Information was obtained from
      eligible prescriptions received over 24-month period using a modified WHO
      prescribing indicator form. The WHO prescribing indicators and the Index of
      Rational Drug Prescribing (IRDP) were used to evaluate prescriptions. Data were
      analyzed and presented as proportions, means, tables, and charts, comparing with
      WHO standards and with findings of similar studies. RESULTS: There were 3908
      eligible prescription orders, with a mean patient age of 3.1 (+/-2.7) years. With
      an average of 2.1 drugs per prescription, 66.8% were written with generic names,
      whereas a single antibiotic was included among 63% of prescriptions with
      antibiotics. Antibiotics and injections were contained in 49.5% and 67.7% of
      prescriptions, respectively. Medications were available in the Essential
      Medicines List in 95.5% of cases. The IRDP obtained is 2.99, against a standard
      of 5. Aminoglycosides, cephalosporins, and penicillins were the most common
      choices, whereas ampicillin/cloxacillin was the most common combination.
      CONCLUSION: Drug prescribing and antibiotic use were generally inappropriate
      compared with ideal standards. Continuous training/retraining on rational drug
      use, periodic monitoring, and use of treatment protocols in tertiary hospitals
      are recommended.

PMID- 29363634
TI  - Evaluation of the cognitive effect of newborn resuscitation training on health
      care workers in selected states in Northern Nigeria.
AB  - BACKGROUND: Neonatal deaths contribute significantly to slower progress in under
      5 mortality reduction. Lack of sufficiently trained birth assistants partly
      contributes to early neonatal deaths. Resuscitation training equips frontline
      health-care workers (HCWs) with requisite knowledge and skills to prevent birth
      asphyxia. OBJECTIVE: The objective of this study was to evaluate the immediate
      impact of newborn resuscitation training on cognitive ability of HCWs. MATERIALS
      AND METHODS: This is a descriptive observational study using pre- and
      posttraining scores obtained by HCWs who were participants in 1-day training on
      emergency newborn resuscitation. The Newborn Resuscitation Manual of the UK
      Resuscitation Council (2006) was used to train HCWs. The course included
      lectures, skill and scenario demonstrations using mannequins, and basic
      resuscitation equipment. Cognitive knowledge was evaluated using a pre- and post
      training questionnaire. Participants' scores were collated, analyzed, and results
      were presented as tables, charts, and descriptive statistics with P < 0.05
      considered statistically significant. RESULTS: A total of 293 HCWs completed the
      course (81 doctors and 212 nurse/midwives), with variable improvements of mean
      posttraining marks over the pretraining scores. Resident doctors obtained
      significantly higher mean pre- and post-training marks with lower mean difference
      than senior doctors and medical officers. The junior nurses obtained
      significantly higher mean pretraining scores compared to the senior nursing
      cadre, while the intermediate nursing cadre obtained significantly higher mean
      posttraining scores compared to senior nurses. CONCLUSION: Resuscitation training
      improved the knowledge of HCWs. Further evaluation could ascertain impacts on
      knowledge/skills' retention and neonatal survival. Preservice training and
      continuing education for frontline HCWs who conduct deliveries are recommended.

PMID- 29363635
TI  - Sparfloxacin-induced nail pigmentation: A case of fixed drug eruption?
AB  - Sparfloxacin, a synthetic, second generation, broad spectrum
      aminodifluoroquinolone antibiotic, has excellent penetration into respiratory
      tissues and has good activity against Gram-positive, Gram-negative, and atypical
      bacteria. Although it is indicated for the treatment of adult community-acquired
      pneumonia and acute exacerbation of chronic bronchitis, its use has been limited
      by phototoxicity which is more common with it than with other quinolones. We
      report a case of a 20-year-old Nigerian woman who developed a diffuse blue-black
      nail pigmentation of thumb and big toe nails, 2 weeks after completing therapy
      with sparfloxacin, and a recurrence of the pigmentation in the same nails 1 year
      after taking the drug again. We think this is likely a case of subungual fixed
      drug eruption. We briefly discuss the causes and mechanisms of drug-induced nail
      pigmentation in general.

PMID- 29363636
TI  - Drug-induced oral erythema multiforme: A diagnostic challenge.
AB  - Trimethoprim-sulfamethoxazole (cotrimoxazole or TMP/SMX) is commonly used for the
      treatment of urinary or lower respiratory tract infections. A comprehensive
      review is presented of the world literature on adverse reactions to TMP/SMX since
      its first use in 1968, when concern was expressed about possible hematologic
      toxicity. The adverse reactions to TMP/SMX occur in approximately 1%-3% of
      persons in general population. Here, we report a case of oral erythema multiforme
      (EM) secondary to TMP/SMX that presented with oral and lip ulcerations typical of
      EM without any skin lesions and highlights the importance of distinguishing them
      from other ulcerative disorders involving oral cavity. The patient was treated
      symptomatically and given tablet prednisolone. The condition improved with
      stoppage of TMP/SMX therapy. It has been reported that primary attacks of oral EM
      is confined to the oral mucosa, but the subsequent attacks can produce more
      severe forms of EM involving the skin. Hence, it is important to identify for
      early diagnosis and management. Although EM is quite common with TMP/SMX, there
      are no reports of oral EM appearing after intake of this drug.

PMID- 29363637
TI  - Neglected Type III growing skull fracture in a 65-Year-Old female.

PMID- 29363638
TI  - Effect of Systolic Cardiac Function on Passive Leg Raising for Predicting Fluid
      Responsiveness: A Prospective Observational Study.
AB  - BACKGROUND: Passive leg raising (PLR) represents a "self-volume expansion (VE)"
      that could predict fluid responsiveness, but the influence of systolic cardiac
      function on PLR has seldom been reported. This study aimed to investigate whether
      systolic cardiac function, estimated by the global ejection fraction (GEF) from
      transpulmonary-thermodilution, could influence the diagnostic value of PLR.
      METHODS: This prospective, observational study was carried out in the surgical
      Intensive Care Unit of the First Affiliated Hospital of Sun Yat-sen University
      from December 2013 to July 2015. Seventy-eight mechanically ventilated patients
      considered for VE were prospectively included and divided into a low-GEF (<20%)
      and a near-normal-GEF (>=20%) group. Within each group, baseline hemodynamics,
      after PLR and after VE (250 ml 5% albumin over 30 min), were recorded. PLR
      induced hemodynamic changes (PLR-Delta) were calculated. Fluid responders were
      defined by a 15% increase of stroke volume (SV) after VE. RESULTS: Twenty-five
      out of 38 patients were responders in the GEF <20% group, compared to 26 out of
      40 patients in the GEF >=20% group. The thresholds of PLR-DeltaSV and PLR-Delta
      cardiac output (PLR-DeltaCO) for predicting fluid responsiveness were higher in
      the GEF >=20% group than in the GEF <20% group (DeltaSV: 12% vs. 8%; DeltaCO: 7%
      vs. 6%), with increased sensitivity (DeltaSV: 92% vs. 92%; DeltaCO: 81% vs. 80%)
      and specificity (DeltaSV: 86% vs. 70%; DeltaCO: 86% vs. 77%), respectively. PLR
      Delta heart rate could predict fluid responsiveness in the GEF >=20% group with a
      threshold value of -5% (sensitivity 65%, specificity 93%) but could not in the
      GEF <20% group. The pressure index changes were poor predictors. CONCLUSIONS: In
      the critically ill patients on mechanical ventilation, the diagnostic value of
      PLR for predicting fluid responsiveness depends on cardiac systolic function.
      Thus, cardiac systolic function must be considered when using PLR. TRIAL
      REGISTRATION: Chinese Clinical Trial Register, ChiCTR-OCH-13004027;
      http://www.chictr.org.cn/showproj.aspx?proj=5540.

PMID- 29363639
TI  - Evaluation of CRUSADE and ACUITY-HORIZONS Scores for Predicting Long-term Out-of
      Hospital Bleeding after Percutaneous Coronary Interventions.
AB  - BACKGROUND: There is scanty evidence concerning the ability of Can Rapid Risk
      Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early
      Implementation of the ACC/AHA Guidelines (CRUSADE) and Acute Catheterization and
      Urgent Intervention Triage Strategy and Harmonizing Outcomes with
      Revascularization and Stents in Acute Myocardial Infarction (ACUITY-HORIZONS)
      scores to predict out-of-hospital bleeding risk after percutaneous coronary
      interventions (PCIs) with drug-eluting stents (DES) in patients receiving dual
      antiplatelet therapy. We aimed to assess and compare the long-term prognostic
      value of these scores regarding out-of-hospital bleeding risk in such patients.
      METHODS: We performed a prospective observational study of 10,724 patients
      undergoing PCI between January and December 2013 in Fuwai Hospital, China. All
      patients were followed up for 2 years and evaluated through the Fuwai Hospital
      Follow-up Center. Major bleeding was defined as Types 2, 3, and 5 according to
      Bleeding Academic Research Consortium Definition criteria. RESULTS: During a 2
      year follow-up, 245 of 9782 patients (2.5%) had major bleeding (MB). CRUSADE
      (21.00 [12.00, 29.75] vs. 18.00 [11.00, 26.00], P < 0.001) and ACUITY-HORIZONS
      (9.00 [3.00, 14.00] vs. 6.00 [3.00, 12.00], P < 0.001) risk scores were both
      significantly higher in the MB than non-MB groups. Both scores showed a moderate
      predictive value for MB in the whole study cohort (area under the receiver
      operating characteristics curve [AUROC], 0.565; 95% confidence interval [CI],
      0.529-0.601, P = 0.001; AUROC, 0.566; 95% CI, 0.529-0.603, P < 0.001,
      respectively) and in the acute coronary syndrome (ACS) subgroup (AUROC: 0.579,
      95% CI: 0.531-0.627, P = 0.001; AUROC, 0.591; 95% CI, 0.544-0.638, P < 0.001,
      respectively). However, neither score was a significant predictor in the non-ACS
      subgroup (P > 0.05). The value of CRUSADE and ACUITY-HORIZONS scores did not
      differ significantly (P > 0.05) in the whole cohort, ACS subgroup, or non-ACS
      subgroup. CONCLUSIONS: CRUSADE and ACUITY-HORIZONS scores showed statistically
      significant but relatively limited long-term prognostic value for out-of-hospital
      MB after PCI with DES in a cohort of Chinese patients. The value of CRUSADE and
      ACUITY-HORIZONS scores did not differ significantly (P > 0.05) in the whole
      cohort, ACS subgroup, or non-ACS subgroup.

PMID- 29363640
TI  - Interferon-Gamma Release Assay is Not Appropriate for the Diagnosis of Active
      Tuberculosis in High-Burden Tuberculosis Settings: A Retrospective Multicenter
      Investigation.
AB  - BACKGROUND: Interferon-gamma release assay (IGRA) has been used in latent
      tuberculosis (TB) infection and TB diagnosis, but the results from different high
      TB-endemic countries are different. The aim of this study was to investigate the
      value of IGRA in the diagnosis of active pulmonary TB (PTB) in China. METHODS: We
      conducted a large-scale retrospective multicenter investigation to further
      evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic
      populations and the factors affecting the performance of the assay. All patients
      who underwent valid T-SPOT.TB assays from December 2012 to November 2015 in six
      large-scale specialized TB hospitals in China and met the study criteria were
      retrospectively evaluated. Patients were divided into three groups: Group 1,
      sputum culture-positive PTB patients, confirmed by positive Mycobacterium
      tuberculosis sputum culture; Group 2, sputum culture-negative PTB patients; and
      Group 3, non-TB respiratory diseases. The medical records of all patients were
      collected. Chi-square tests and Fisher's exact test were used to compare
      categorical data. Multivariable logistic analyses were performed to evaluate the
      relationship between the results of T-SPOT in TB patients and other factors.
      RESULTS: A total of 3082 patients for whom complete information was available
      were included in the investigation, including 905 sputum culture-positive PTB
      cases, 914 sputum culture-negative PTB cases, and 1263 non-TB respiratory disease
      cases. The positive rate of T-SPOT.TB was 93.3% in the culture-positive PTB group
      and 86.1% in the culture-negative PTB group. In the non-PTB group, the positive
      rate of T-SPOT.TB was 43.6%. The positive rate of T-SPOT.TB in the culture
      positive PTB group was significantly higher than that in the culture-negative PTB
      group (chi2 = 25.118, P < 0.01), which in turn was significantly higher than that
      in the non-TB group (chi2 = 566.116, P < 0.01). The overall results were as
      follows: sensitivity, 89.7%; specificity, 56.37%; positive predictive value,
      74.75%; negative predictive value, 79.11%; and accuracy, 76.02%. CONCLUSIONS:
      High false-positive rates of T-SPOT.TB assays in the non-TB group limit the
      usefulness as a single test to diagnose active TB in China. We highly recommend
      that IGRAs not be used for the diagnosis of active TB in high-burden TB settings.

PMID- 29363641
TI  - Scarring Airway Stenosis in Chinese Adults: Characteristics and Interventional
      Bronchoscopy Treatment.
AB  - BACKGROUND: Scarring airway stenosis is commonly seen in China as compared to
      other developed countries, due to the high prevalence of tuberculosis. Nowadays,
      interventional bronchoscopy treatment has been widely used to treat this disease
      in China. This study demonstrated the characteristics of scarring airway stenosis
      in Chinese adults and retrospectively evaluated the efficacy of interventional
      bronchoscopy treatment of this disease. METHODS: Patients with scarring airway
      stenosis from 18 tertiary hospitals were enrolled between January 2013 and June
      2016. The causes, site, and length of scarring airway stenosis were analyzed, and
      the efficacy of the interventional bronchoscopy treatment was evaluated. RESULTS:
      The final study cohort consisted of 392 patients. Endotracheobronchial
      tuberculosis (EBTB) was the most common cause of scarring airway stenosis
      (305/392, 77.8%) in Chinese adults with a high rate of incidence in young women.
      The left main bronchus was most susceptible to EBTB, and most posttuberculosis
      airway scarring stenosis length was 1.1-2.0 cm. The average clinical success rate
      of interventional bronchoscopy treatment for scarring airway stenosis in Chinese
      patients is 60.5%. The stent was inserted in 8.7% scarring airway stenosis in
      China. CONCLUSIONS: Scarring airway stenosis exhibits specific characteristics in
      Chinese patients. Interventional bronchoscopy is a useful and safe treatment
      method for the disease.

PMID- 29363642
TI  - Anterior Subcutaneous Transposition of the Ulnar Nerve Affects Elbow Range of
      Motion: A Mean 13.5 Years of Follow-up.
AB  - BACKGROUND: Surgical decompression of the ulnar nerve is effective for cubital
      tunnel syndrome. However, deep approaches may result in iatrogenic elbow
      stiffness. This long-term study was to evaluate the range of motion (ROM) of the
      elbow and functional outcomes after anterior subcutaneous transposition. METHODS:
      A total of 115 patients (78 male and 37 female; mean age: 46.6 years) who
      underwent anterior subcutaneous transposition of the ulnar nerve between 2001 and
      2005 were evaluated retrospectively; mean follow-up was 13.5 years. Elbow ROM was
      measured as flexion arc, flexion, and extension preoperatively and at the final
      follow-up, and compared via a mixed analysis of variance adjusting for age.
      Neuropathy was assessed preoperatively using a modified McGowan neuropathy grade
      and postoperatively using modified Wilson-Krout criteria. An ordinal logistic
      regression analysis used postoperative modified Wilson-Krout criteria as the
      outcome and preoperative factors as predictors. RESULTS: Preoperative McGowan
      grades were Grade 1 in 14 patients (12.2%), Grade 2A in 28 (24.3%), Grade 2B in
      53 (46.1%), and Grade 3 in 20 (17.4%) patients. Postoperatively, 66 patients
      (57.4%) had excellent results, 26 (22.6%) had good results, 16 (13.9%) had fair
      results, and 7 (6.1%) had poor results at the final follow-up, as per the Wilson
      Krout criteria. There were no complications. Pre- and postoperative elbow ROM was
      significantly decreased in patients with previous trauma or surgery of the elbow
      compared with those without (P < 0.05). Anterior subcutaneous transposition of
      the ulnar nerve did not significantly affect elbow ROM regardless of previous
      trauma or surgical history nor preoperative ROM (P > 0.05), after adjusting for
      age. Patients with prolonged symptoms prior to surgery and worse neuropathy
      tended to have less satisfactory functional outcomes (P < 0.05), after adjusting
      for covariates. CONCLUSIONS: Anterior subcutaneous transposition of the ulnar
      nerve is an effective and reliable treatment of cubital tunnel syndrome with
      satisfactory outcomes and minimal effect on elbow ROM.

PMID- 29363643
TI  - Clinical Significance of Pelvic Peritonization in Laparoscopic Dixon Surgery.
AB  - BACKGROUND: Pelvic floor peritoneum reconstruction is a key step in various
      standard resections for open radical rectal cancer. However, during endoscopic
      surgery, most surgeons do not close the pelvic floor peritoneum. This study aims
      to evaluate the efficacy of pelvic peritonization during laparoscopic Dixon
      surgery using an observational study. METHODS: A total of 189 patients, who
      underwent laparoscopic Dixon surgery at Tianjin Union Medical Center, China, were
      analyzed retrospectively. All of the cases were divided into two groups according
      to the differences of surgical procedure. The 92 patients in Group A (observation
      group) underwent pelvic peritonization and the 97 patients in Group B (control
      group) did not undergo this procedure. Postoperative complications were observed
      in the two groups, compared, and analyzed using the Chi-square or Fisher's exact
      test. RESULTS: The incidence of anastomotic leakage was significantly lower in
      Group A than in Group B (P = 0.014). A significant difference was found in the
      postoperative short-term (P = 0.029) and long-term (P = 0.029) ileus rates
      between the two groups, with Group A exhibiting a lower rate than Group B.
      Patients in Group A had significantly lower rates of postoperative infections
      than those in Group B (chi2 = 7.606, P = 0.006; chi2 = 4.464, P = 0.035).
      Patients in Group A had significantly lower rates of deep venous thrombosis than
      those in Group B (chi2 = 8.531, P = 0.003). CONCLUSIONS: Pelvic peritonization
      effectively reduces postoperative complications, such as anastomotic leakage,
      which warrants its increased use in laparoscopic surgery.

PMID- 29363644
TI  - Situational Analysis of Low-density Lipoprotein Cholesterol Control and the Use
      of Statin Therapy in Diabetes Patients Treated in Community Hospitals in Nanjing,
      China.
AB  - BACKGROUND: Comprehensive management of diabetes should include management of its
      comorbid conditions, especially cardiovascular complications, which are the
      leading cause of morbidity and mortality among patients with diabetes.
      Dyslipidemia is a comorbid condition of diabetes and a risk factor for
      cardiovascular complications. Therefore, lipid level management is a key of
      managing patients with diabetes successfully. However, it is not clear that how
      well dyslipidemia is managed in patients with diabetes in local Chinese health
      care communities. This study aimed to assess how well low-density lipoprotein
      cholesterol (LDL-C) was managed in Nanjing community hospitals, China. METHODS:
      We reviewed clinical records of 7364 diabetic patients who were treated in eleven
      community hospitals in Nanjing from October 2005 to October 2014. Information
      regarding LDL-C level, cardiovascular risk factors, and use of lipid-lowering
      agents were collected. RESULTS: In patients without history of cardiovascular
      disease (CVD), 92.1% had one or more CVD risk factors, and the most common CVD
      risk factor was dyslipidemia. The overall average LDL-C level was 2.80 +/- 0.88
      mmol/L, which was 2.62 +/- 0.90 mmol/L and 2.82 +/- 0.87 mmol/L in patients with
      and without CVD history respectively. Only 38% of all patients met the target
      goal and 37.3% of patients who took lipid-lowering agents met target goal.
      Overall, 24.5% of all patients were on lipid-lowering medication, and 36.3% of
      patients with a CVD history and 20.9% of patients without CVD history took
      statins for LDL-C management. The mean statin dosage was 13.9 +/- 8.9 mg.
      CONCLUSIONS: Only a small portion of patients achieved target LDL-C level, and
      the rate of using statins to control LDL-C was low. Managing LDL-C with statins
      in patients with diabetes should be promoted, especially in patients without a
      CVD history and with one or more CVD risk factors.

PMID- 29363645
TI  - Effects of Repetitive Transcranial Magnetic Stimulation Treatment on Event
      Related Potentials in Schizophrenia.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) and event-related
      potentials (ERPs) are a noninvasive technique that widely used in
      neurophysiological field. Although rTMS has shown clinical utility for a number
      of neurological conditions, Recently,there was little understanding of the the
      efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and
      after rTMS treatment. The objective of this study was to investigate the
      characteristics of N400, mismatch negativity (MMN), and P300 before and after
      treatment with rTMS in SZ. METHODS: One hundred and twenty-seven SZ patients
      hospitalized in Shanghai Mental Health Center from March 2015 to July 2017,
      divided into two groups (85 patients were recruited as rTMS group and 42 were
      recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the
      staff and refresher staff in our hospital were recruited at the same time. A
      Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present
      experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After
      rTMS treatment, N400, P300, and MMN characteristics were compared with those
      before treatment and NC group. RESULTS: Compared with NC, the SZ patients
      exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN
      amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400
      amplitudes in the frontal area (elicited by idioms with same phonic and different
      shape and meaning and with different phonic, shape, and meaning) were increased
      in the SZ patients (P < 0.05). However, there was no significant change in N400
      before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for
      MMN and target P300 also increased in SZ patients after rTMS treatment (P <
      0.05). CONCLUSIONS: Based on our preliminary findings, we believe that the
      combined usage of N400, MMN, and P300 could be a valuable index and an
      electrophysiological reference in evaluating the effects of rTMS treatment in SZ
      patients.

PMID- 29363646
TI  - Comparison between Bilateral and Unilateral Sudden Sensorineural Hearing Loss.
AB  - BACKGROUND: Bilateral sudden sensorineural hearing loss (BSSHL) is rare and
      assumed to be a different clinical entity compared to unilateral SSHL (USSHL).
      This study examined the differences between the idiopathic BSSHL and USSHL.
      METHODS: Forty-six sequential BSSHL patients (Se-BSSHL) and 68 simultaneous BSSHL
      (Si-BSSHL) were consecutively admitted between June 2008 and December 2015. Two
      sets of patients served as control groups: (1) USSHL patients with healthy
      contralateral ear and (2) USSHL patients with contralateral preexisting hearing
      loss (USSHLwCHL). We retrospectively analyzed differences among four cohorts
      using analysis of variance, Kruskal-Wallis test, Welch's t-test, and Chi-square
      test as appropriate before and after propensity score matching (PSM) based on
      age, gender, and body mass index (BMI). RESULTS: The prevalence of idiopathic
      BSSHL was 8.6% (114/1329) among the total SSHL patients. In the total cohort,
      USSHL patients tended to be younger, female, and tended to have lower BMI, renal
      parameters, and total cholesterol in addition to higher high-density lipoprotein
      compared to the other three groups. Most routine blood indicators, some
      coagulation markers, and immunoglobulin M (H = 13.4, P = 0.004) were
      significantly different among the study groups. After PSM, the major significant
      differences were found in audiometric characteristics. Si-BSSHL and Se-BSSHL
      patients demonstrated similar hearing thresholds as USSHL but were significantly
      better than the USSHLwCHL patients across most frequencies before and after
      treatment (H = 30.0, P < 0.001 for initial hearing and H = 12.0, P = 0.007 for
      final hearing). Moreover, the BSSHL patients showed different hearing loss
      distribution patterns (more descending type, chi2 = 33.8, P = 0.001) with less
      hearing gain (H = 17.5, P < 0.001) compared to the USSHL patients. CONCLUSIONS:
      Idiopathic BSSHL is a relatively rare subtype of SSHL with a higher rate of
      descending audiogram type and inferior hearing outcome rather than being
      classified as a completely different disease entity compared to USSHL.

PMID- 29363647
TI  - Elevated Levels of Soluble ST2 were Associated with Rheumatoid Arthritis Disease
      Activity and Ameliorated Inflammation in Synovial Fibroblasts.
AB  - BACKGROUND: Much evidence has demonstrated that interleukin (IL)-33 plays an
      important role in rheumatoid arthritis (RA). However, there have been limited
      studies about soluble ST2, a receptor for IL-33, in RA. The aims of this study
      were to detect the levels of ST2 in the serum and synovial fluid of RA patients
      and to reveal the association of these levels with disease activity and the
      function of ST2 in RA. METHODS: A total of 56 RA patients and 38 age-matched
      healthy controls were enrolled in this study. Synovial fluid samples were
      collected from another 30 RA patients and 20 osteoarthritis patients. Serum and
      synovial fluid levels of ST2 were measured by ELISA. In addition, the levels of
      ST2 in the serum of RA patients before and after therapy were detected. The
      function of ST2 in RA was revealed by the results of an in vitro cell assay,
      where recombinant ST2 proteins were used to treat peripheral blood mononuclear
      cells (PBMCs) and RA synovial fibroblasts (RASFs). RESULTS: Serum-soluble ST2
      levels were significantly higher in RA patients (127.14 +/- 61.43 pg/ml) than
      those in healthy controls (78.37 +/- 41.93 pg/ml, P < 0.01). Synovial fluid
      soluble ST2 levels (41.90 +/- 33.58 pg/ml) were much higher in RA patients than
      those in osteoarthritis patients (19.71 +/- 16.72 pg/ml, P < 0.05). RA patients
      who received effective therapy for 6 months showed decreased serum-soluble ST2
      levels (113.01 +/- 53.90 pg/ml) compared to baseline (139.59 +/- 68.36 pg/ml) (P
      = 0.01). RA patients with high disease activity had higher serum-soluble ST2
      levels (162.02 +/- 56.78 pg/ml) than those with low disease activity (94.67 +/-
      40.27 pg/ml, P = 0.001). Soluble ST2 did not affect IL-1beta, IL-6, IL-8, or
      tumor necrosis factor-alpha (TNF-alpha) expression in PBMCs from RA patients.
      However, soluble ST2 ameliorated the expressions of IL-33 and IL-1beta but not
      that of IL-6, IL-8, or TNF-alpha in resting RASFs. Interestingly, in the RASFs
      stimulated by TNF-alpha plus IL-1beta, soluble ST2 showed extensive suppressive
      effects on the expression of IL-6, IL-8, and TNF-alpha. CONCLUSION: Elevated
      levels of ST2 in the serum and synovial fluid were associated with disease
      activity and ameliorated IL-33 expression and IL-33-induced inflammation in
      RASFs, suggesting that soluble ST2 might be a potential therapeutic candidate for
      RA.

PMID- 29363648
TI  - Increased Efficacy of Antivenom Combined with Hyperbaric Oxygen on
      Deinagkistrodon acutus Envenomation in Adult Rats.
AB  - BACKGROUND: Snakebites are a neglected threat to global human health with a high
      morbidity rate. The present study explored the efficacy of antivenom with
      hyperbaric oxygen (HBO) intervention on snakebites, which could provide the
      experimental basis for clinical adjuvant therapy. METHODS: Male Sprague-Dawley
      rats (n = 96) were randomized into four groups: the poison model was established
      by injecting Deinagkistrodon acutus (D. acutus) venom (0.8 LD50) via the caudal
      vein; the antivenom group was injected immediately with specific antivenom via
      the caudal vein after successful establishment of the envenomation model; and the
      antivenom + HBO group was exposed to HBO environment for 1 h once at
      predetermined periods of 0 h, 4 h, 12 h, and 23 h after antivenin administration.
      Each HBO time point had six rats; the control group was left untreated. The rats
      in the experimental group were euthanized at the corresponding time points after
      HBO therapy, and brain tissue and blood were harvested immediately. Hematoxylin
      and eosin (H&E) staining was used to investigate the pathological changes in the
      rat brain. Immunohistochemistry (IHC), real-time polymerase chain reaction (PCR),
      and Western blotting were used to detect the expression of Nestin mRNA and
      protein in the subventricular zone (SVZ) of the brain. The levels of coagulation
      function (prothrombin time, activated partial thromboplastin time [APTT], and
      fibrinogen) and oxidation/antioxidation index (malondialdehyde [MDA] and
      superoxide dismutase [SOD]) were analyzed. Data were analyzed using one-way
      analysis of variance. RESULTS: The brain tissue from rats in the poison model was
      observed for pathological changes using H&E staining. Tissues showed edema,
      decreased cell number, and disordered arrangement in the SVZ in the snake venom
      group. The antivenom - HBO intervention significantly alleviated these
      observations and was more prominent in the antivenom + HBO group. The serum
      levels of SOD and MDA in the snake venom group were increased and the antivenom -
      HBO intervention further increased the SOD levels but significantly decreased the
      MDA levels; however, this was enhanced within 1 h after HBO administration (MDA:
      F = 5.540, P = 0.008, SOD: F = 7.361, P = 0.000). Activated partial
      thromboplastin time (APTT) was significantly abnormal after venom administration
      but improved after antivenom and was even more significant in the antivenom + HBO
      group 5 h after envenomation (F = 25.430, P = 0.000). Only a few nestin-positive
      cells were observed in the envenomation model. The expression levels were
      significant in the antivenom and antivenom + HBO groups within 1 and 5 h after
      envenomation and were more significant in the antivenom + HBO group as determined
      by IHC, real-time PCR, and Western blotting (P < 0.05). D. acutus envenomation
      has neurotoxic effects in the brain of rats. CONCLUSIONS: Antivenin and HBO,
      respectively, induced a neuroprotective effect after D. acutus envenomation by
      attenuating brain edema, upregulating nestin expression in SVZ, and improving
      coagulopathy and oxidative stress. The intervention efficacy of antivenom with
      HBO was maximum within 5 h after envenomation and was more efficacious than
      antivenom alone.

PMID- 29363649
TI  - Role of the Ca2+-Calcineurin-Nuclear Factor of Activated T cell Pathway in
      Mitofusin-2-Mediated Immune Function of Jurkat Cells.
AB  - BACKGROUND: Mitofusin-2 (MFN2), a well-known mitochondrial fusion protein, has
      been shown to participate in innate immunity, but its role in mediating adaptive
      immunity remains poorly characterized. In this study, we explored the potential
      role of MFN2 in mediating the immune function of T lymphocytes. METHODS: We
      manipulated MFN2 gene expression in Jurkat cells via lentiviral transduction of
      MFN2 small interfering RNA (siRNA) or full-length MFN2. After transduction, the
      immune response and its underlying mechanism were determined in Jurkat cells. One
      way analysis of variance and Student's t-test were performed to determine the
      statistical significance between the groups. RESULTS: Overexpression of MFN2
      enhanced the immune response of T lymphocytes by upregulating Ca2+ (359.280 +/-
      10.130 vs. 266.940 +/- 10.170, P = 0.000), calcineurin (0.513 +/- 0.014 vs. 0.403
      +/- 0.020 nmol/L, P = 0.024), and nuclear factor of activated T cells (NFATs)
      activation (1.040 +/- 0.086 vs. 0.700 +/- 0.115, P = 0.005), whereas depletion of
      MFN2 impaired the immune function of T lymphocytes by downregulating Ca2+
      (141.140 +/- 14.670 vs. 267.060 +/- 9.230, P = 0.000), calcineurin (0.054 +/-
      0.030 nmol/L vs. 0.404 +/- 0.063 nmol/L, P = 0.000), and NFAT activation (0.500
      +/- 0.025 vs. 0.720 +/- 0.061, P = 0.012). Furthermore, upregulated calcineurin
      partially reversed the negative effects of MFN2 siRNA on T cell-mediated immunity
      evidenced by elevations in T cell proliferation (1.120 +/- 0.048 vs. 0.580 +/-
      0.078, P = 0.040), interleukin-2 (IL-2) production (473.300 +/- 24.100 vs.
      175.330 +/- 12.900 pg/ml, P = 0.000), and the interferon-gamma/IL-4 ratio (3.080
      +/- 0.156 vs. 0.953 +/- 0.093, P = 0.000). Meanwhile, calcineurin activity
      inhibitor depleted the positive effects of overexpressed MFN2 on T cells
      function. CONCLUSIONS: Our findings suggest that MFN2 may regulate T cell immune
      functions primarily through the Ca2+-calcineurin-NFAT pathway. MFN2 may represent
      a potential therapeutic target for T cell immune dysfunction-related diseases.

PMID- 29363650
TI  - MicroRNA Profiling of Transgenic Mice with Myocardial Overexpression of
      Nucleolin.
AB  - BACKGROUND: Nucleolin (NCL) is the most abundant RNA-binding protein in the cell
      nucleolus and plays an important role in chromatin stability, ribosome assembly,
      ribosomal RNA maturation, ribosomal DNA transcription, nucleocytoplasmic
      transport, and regulation of RNA stability and translation efficiency. In
      addition to its anti-apoptotic properties, the underlying mechanisms associated
      with NCL-related roles in different cellular processes remain unclear. In this
      study, the effect of NCL on microRNA (miRNA) expression was evaluated by
      generating transgenic mice with myocardial overexpression of NCL and by analyzing
      microarrays of mature and precursor miRNAs from mice. METHODS: Using
      microinjection of alpha-MyHc clone 26-NCL plasmids, we generated transgenic mice
      with myocardial overexpression of NCL firstly, and then mature and precursor
      miRNAs expression profiles were analyzed in NCL transgenic mice (n = 3) and wild
      type (WT) mice (n = 3) by miRNA microarrays. Statistical Package for the Social
      Sciences version 16.0 software (SPSS, Inc., Chicago, IL, USA) was used to perform
      Student's t-test, and statistical significance was determined at P < 0.05.
      RESULTS: Several miRNAs were found to be differentially expressed, of which 11
      were upregulated and 4 were downregulated in transgenic mice with myocardial
      overexpression of NCL compared to those in WT mice. Several differentially
      expressed miRNAs were subsequently confirmed and quantified by real-time
      quantitative reverse transcription-polymerase chain reaction. Bioinformatics
      analysis was used for the prediction of miRNA targets. Furthermore, in vitro
      experiments showed that NCL regulated miR-21 expression following hydrogen
      peroxide preconditioning. CONCLUSIONS: Myocardial-protection mechanisms exerted
      by NCL might be mediated by the miRNAs identified in this study.

PMID- 29363652
TI  - Sustained Ventricular Tachycardia Secondary to Cardiac Metastasis of Lung Cancer.

PMID- 29363651
TI  - Rationale and Study Design for a Single-Arm Phase IIa Study Investigating
      Feasibility of Preventing Ischemic Cerebrovascular Events in High-Risk Patients
      with Acute Non-disabling Ischemic Cerebrovascular Events Using Remote Ischemic
      Conditioning.
AB  - BACKGROUND: Acute minor ischemic stroke (AMIS) or transient ischemic attack (TIA)
      is a common cerebrovascular event with a considerable high recurrence. Prior
      research demonstrated the effectiveness of regular long-term remote ischemic
      conditioning (RIC) in secondary stroke prevention in patients with intracranial
      stenosis. We hypothesized that RIC can serve as an effective adjunctive therapy
      to pharmacotherapy in preventing ischemic events in patients with AMIS/TIA. This
      study aimed to investigate the feasibility, safety, and preliminary efficacy of
      daily RIC in inhibiting cerebrovascular/cardiovascular events after AMIS/TIA.
      METHODS: This is a single-arm, open-label, multicenter Phase IIa futility study
      with a sample size of 165. Patients with AMIS/TIA receive RIC as an additional
      therapy to secondary stroke prevention regimen. RIC consists of five cycles of 5
      min inflation (200 mmHg) and 5-min deflation of cuffs on bilateral upper limbs
      twice a day for 90 days. The antiplatelet strategy is based on individual
      physician's best practice: aspirin alone, clopidogrel alone, or combination of
      aspirin and clopidogrel. We will assess the recurrence rate of ischemic
      stroke/TIA within 3 months as the primary outcomes. CONCLUSIONS: The data
      gathered from the study will be used to determine whether a further large-scale,
      multicenter randomized controlled Phase II trial is warranted in patients with
      AMIS/TIA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03004820;
      https://www.clinicaltrials.gov/ct2/show/NCT03004820.

PMID- 29363653
TI  - Complex Heterozygous Mutation in the T-cell Immune Regulator 1 Gene Associated
      with Severe Ocular Characteristics of Osteopetrosis in an Infant.

PMID- 29363654
TI  - Severe Mediastinal Abscess after Endobronchial Ultrasound with Transbronchial
      Needle Aspiration.

PMID- 29363655
TI  - Characteristics of Adult Fractures in Emergency Department in Beijing Jishuitan
      Hospital during 2009-2016.

PMID- 29363656
TI  - Subsequent Multidrug-Resistant Bacteremia Is a Risk Factor for Short-Term
      Mortality of Patients with Ventilator-Associated Pneumonia Caused by
      Acinetobacter baumannii in Intensive Care Unit: A Multicenter Experience.

PMID- 29363657
TI  - Granulation Tissue-type Hemangioma in the Internal Jugular Vein.

PMID- 29363658
TI  - One Eye Suffering from Ocular Decompression Retinopathy after Trabeculectomy in a
      Patient with Juvenile Open-Angle Glaucoma.

PMID- 29363659
TI  - Retrieval of a Disconnected Left Atrial Appendage Occluder with Endoscopic
      Grasping Forceps.

PMID- 29363660
TI  - Acute ST-elevation Myocardial Infarction after Upper Gastrointestinal Bleeding: A
      Clinical Dilemma of Antiplatelet Therapy.

PMID- 29363661
TI  - Splenic Injury: An Unusual Complication of Colonoscopy.

PMID- 29363662
TI  - Adrenal Collision Tumor Composed of Adrenocortical Adenoma and Pheochromocytoma.

PMID- 29363663
TI  - Metformin Might Inhibit Virus through Increasing Insulin Sensitivity.

PMID- 29363664
TI  - Preoperative Diagnosis of Endometriosis.

PMID- 29363665
TI  - Evaluation of the longitudinal deformation of the left ventricular myocardium in
      subjects with impaired fasting glucose with and without increased glycated
      hemoglobin.
AB  - OBJECTIVE: Prediabetes comprises a heterogeneous group because of the poor
      concordance of its definition. The aim of our study was to evaluate the
      longitudinal deformation of the left ventricular (LV) myocardium at the two
      opposite ends of the prediabetes spectrum as defined by fasting blood sugar and
      glycated hemoglobin (HbA1c). METHODS: Eighty consecutive subjects in a cross
      sectional single-center study with impaired fasting glucose (IFG) (100-126 mg/dL)
      and without significant epicardial coronary artery stenosis seen on selective
      coronary angiography were included in our study and were divided into two groups
      based on their HbA1c levels (<5.7% and 5.7%-6.4%). The longitudinal deformation
      of the LV myocardium was compared between the two groups using two-dimensional
      speckle-tracking echocardiography (2DSTE). RESULTS: The Student t-test, Mann
      Whitney U test, or X2 test was used for data analysis, whichever was appropriate.
      The systolic strain (-16.1%+/-2.0 vs. -16.8%+/-2.4; p=0.214), systolic strain
      rate (-1.3+/-0.2 s-1 vs. -1.4+/-0.2 s-1; p=0.403), and early and late-diastolic
      strain rates (1.4+/-0.3 s-1 vs. 1.5+/-0.3 s-1; p=0.456 and 0.9+/-0.1 s-1 vs.
      1.0+/-0.2 s-1; p=0.684, respectively) of the LV myocardium were not statistically
      different between the IFG subjects with and without increased HbA1c as detected
      using 2DSTE. CONCLUSION: The longitudinal deformation of the LV myocardium as
      detected using 2DSTE in the subjects without significant epicardial coronary
      artery stenosis was not statistically significantly different between the IFG
      subjects with and without increased HbA1c.

PMID- 29363666
TI  - Serum interleukin-17 levels predict inflammatory activity in patients with
      autoimmune hepatitis.
AB  - INTRODUCTION    The etiology of autoimmune hepatitis (AIH) is unclear, with
      molecular mimicry between host and viral/drug antigens being the most plausible
      mechanism initiating the immune cascade that induces hepatocyte injury. Finding a
      serologic parameter that closely relates to the liver histology would be
      beneficial for monitoring AIH activity and optimizing treatment. OBJECTIVES    We
      studied serum interleukin (IL)-17 levels and IL-17 activators (IL-6 and
      transforming growth factor beta1 [TGF-beta1]) in treatment-naive and
      immunosuppressed patients with AIH. We also analyzed the relationships between
      these cytokines and histological inflammation scores. PATIENTS AND METHODS    A
      total of 44 patients with confirmed AIH were enrolled to the study (22 treatment
      naive patients and 22 patients in clinical remission after at least 3 years of
      immunosuppression). Liver biopsies were performed, and the histological grading
      of inflammatory activity was performed by a single pathologist. The control group
      comprised 30 healthy age- and sex-matched subjects. Serum IL-17, IL-6, and TGF
      beta1 levels were measured by a quantitative sandwich enzyme immunoassay. RESULTS
      Serum IL-17, IL-6, and TGF-beta1 levels were higher in treatment-naive
      patients compared with controls (23.2 pg/ml vs 15.3 pg/ml, P = 0.0001; 5.20 pg/ml
      vs 1.42 pg/ml, P = 0.0001; and 40.5 ng/ml vs 30.1 ng/ml, P = 0.04; respectively).
      In treatment-naive patients, serum IL-17 negatively correlated with hepatic
      inflammation (r = -0.63, P = 0.01). A reduced serum IL-17 concentration
      correlated with an increased TGF-beta1 concentration in patients in clinical
      remission (r = -0.51, P = 0.03). CONCLUSIONS    Serum IL-17 levels may be a
      useful parameter for assessing disease activity in patients with AIH.

PMID- 29363667
TI  - Curcumol Controls Choriocarcinoma Stem-Like Cells Self-Renewal via Repression of
      DNA Methyltransferase (DNMT)- and Histone Deacetylase (HDAC)-Mediated Epigenetic
      Regulation.
AB  - BACKGROUND Cancer stem cells (CSCs), in choriocarcinoma and other carcinomas,
      possess the ability of self-renewal and multilineage differentiation potential.
      We previous isolated choriocarcinoma cancer stem-like cells (CSLCs), which hold
      the stemness characteristics of CSCs. Epigenetic modifications have emerged as
      drivers in tumorigenesis, but the mechanisms of CSCs are largely unknown, and new
      drug therapies are needed to break the persistence of CSCs. MATERIAL AND METHODS
      Quantitative real-time PCR (qRT-PCR) and Western blot analysis were performed to
      detect the expression of DNMTs, HDACs, and stemness-genes. DNMTs and HDACs
      silencing and overexpressing lentivirus were transfected into JEG-3 cells to
      investigate the epigenetic functions in CSLCs. In vivo expression of curcumol
      effects of CSLCs on DNMTs and HDACs were analyzed by immunohistochemistry.
      RESULTS Expression of DNMT1, DNMT3b, HDAC1, and HDAC3 were increased in
      choriocarcinoma CSLCs. Consistent with the inhibitory effect of 5-AzaC and TSA on
      CSLCs, DNMT/HDAC knockdown displayed significant repression of self-renewal in
      CSLCs. Curcumol inhibited the stemness ability of CSLCs in vitro and in vivo, and
      the inhibitory effect we observed was mediated in part through repressing
      activity of DNMTs and HDACs. Importantly, curcumol showed a better effect than
      DNMT and HDAC inhibitors combined in eliminating CSLCs. CONCLUSIONS These
      findings indicate that DNMT- and HDAC-mediated epigenetic regulation plays an
      important role in the biology of choriocarcinoma CSLCs, and curcumol has the
      potential to be a new drug to fight CSLCs, warranting further investigation of
      epigenetic-based therapies.

PMID- 29363668
TI  - Leptin receptor q223r polymorphism influences neutrophil mobilization after
      Clostridium difficile infection.
AB  - Clostridium difficile is the leading cause of nosocomial infections in the United
      States. Clinical disease outcomes after C. difficile infection (CDI) are
      dependent on intensity of host inflammatory responses. Specifically, peak
      peripheral white blood cell (WBC) count >20 * 109 l-1 is an indicator of adverse
      outcomes in CDI patients, and is associated with higher 30-day mortality. We show
      that homozygosity for a common single nucleotide polymorphism (Q to R mutation in
      leptin receptor that is present in up to 50% of people), significantly increases
      the risk of having peak peripheral WBC count >20 * 109 l-1 (odds ratio=5.41;
      P=0.0023) in CDI patients. In a murine model of CDI, we demonstrate that mice
      homozygous for the same single nucleotide polymorphism (RR mice) have more blood
      and tissue leukocytes (specifically neutrophils), exaggerated tissue
      inflammation, and higher mortality as compared with control mice, despite similar
      pathogen burden. Further, we show that neutrophilia in RR mice is mediated by gut
      microbiota-directed expression of CXC chemokine receptor 2 (CXCR2), which
      promotes the release of neutrophils from bone marrow reservoir. Overall these
      studies provide novel mechanistic insights into the role of human genetic
      polymorphisms and gut microbiota in regulating the fundamental biological process
      of CDI-induced neutrophilia.

PMID- 29363669
TI  - Histamine drives severity of innate inflammation via histamine 4 receptor in
      murine experimental colitis.
AB  - Ulcerative colitis (UC) patients exhibit elevated histamine, but how histamine
      exacerbates disease is unclear as targeting histamine 1 receptor (H1R) or H2R is
      clinically ineffective. We hypothesized that histamine functioned instead through
      the other colon-expressed histamine receptor, H4R. In humans, UC patient biopsies
      exhibited increased H4R RNA and protein expression over control tissue, and
      immunohistochemistry showed that H4R was in proximity to immunopathogenic
      myeloperoxidase-positive neutrophils. To characterize this association further,
      we employed both the oxazolone (Ox)- and dextran sulfate sodium (DSS)-induced
      experimental colitis mouse models and also found upregulated H4R expression. Mast
      cell (MC)-derived histamine and H4R drove experimental colitis, as H4R-/- mice
      had lower symptom scores, neutrophil-recruitment mediators (colonic interleukin-6
      (IL-6), CXCL1, CXCL2), and mucosal neutrophil infiltration than wild-type (WT)
      mice, as did MC-deficient KitW-sh/W-sh mice reconstituted with histidine
      decarboxylase-deficient (HDC-/-) bone marrow-derived MCs compared with WT
      reconstituted mice; adaptive responses remained intact. Furthermore, Rag2-/- *
      H4R-/- mice had reduced survival, exacerbated colitis, and increased bacterial
      translocation than Rag2-/- mice, revealing an innate protective antibacterial
      role for H4R. Taken together, colonic MC-derived histamine initiates granulocyte
      infiltration into the colonic mucosa through H4R, suggesting alternative
      therapeutic targets beyond adaptive immunity for UC.

PMID- 29363670
TI  - Noxa/HSP27 complex delays degradation of ubiquitylated IkBalpha in airway
      epithelial cells to reduce pulmonary inflammation.
AB  - IFN-gamma is known as a pro-inflammatory cytokine, but can also block
      inflammation in certain chronic diseases although the underlying mechanisms are
      poorly understood. We found that IFN-gamma rapidly induced Noxa expression and
      that extent of inflammation by repeated house dust mite exposure was enhanced in
      noxa-/- compared with noxa+/+ mice. Noxa expression blocked transforming necrosis
      factor alpha (TNF-alpha)-induced nuclear translocation of nuclear factor kappa
      light-chain-enhancer of activated B cells (NF-kappaB) and the production of pro
      inflammatory cytokines. Noxa did not affect TNF-alpha-induced IkappaBalpha
      phosphorylation but the degradation of 48-chain-ubiquitylated IkappaBalpha. The
      Cys25 of Noxa was cross-linked with Cys137 of phospho-HSP27 and both proteins
      were required for blocking the degradation of ubiquitylated IkappaBalpha. Because
      phospho-HSP27 is present in airway epithelial cells and not in fibroblasts or
      thymocytes, we generated transgenic mice that inducibly expressed Noxa in airway
      epithelia. These mice showed protection from allergen-induced inflammation and
      mucous cell metaplasia by blocking nuclear translocation of NF-kappaB. Further,
      we identified a Noxa-derived peptide that prolonged degradation of 48-chain
      ubiquitylated IkappaBalpha, blocked nuclear translocation of NF-kappaB, and
      reduced allergen-induced inflammation in mice. These results suggest that the
      anti-inflammatory role of the Noxa protein may be restricted to airway epithelial
      cells and the use of Noxa for therapy of chronic lung diseases may be associated
      with reduced side effects.

PMID- 29363671
TI  - Intestinal epithelial Toll-like receptor 4 prevents metabolic syndrome by
      regulating interactions between microbes and intestinal epithelial cells in mice.
AB  - Little is known about the pathogenesis of metabolic syndrome, although Toll-like
      receptor 4 (TLR4) has been implicated. We investigated whether TLR4 in the
      intestinal epithelium regulates metabolic syndrome by coordinating interactions
      between the luminal microbiota and host genes that regulate metabolism. Mice
      lacking TLR4 in the intestinal epithelium (TLR4DeltaIEC), but not mice lacking
      TLR4 in myeloid cells nor mice lacking TLR4 globally, developed metabolic
      syndrome; these features were not observed in TLR4DeltaIEC mice given
      antibiotics. Metagenomic analysis of the fecal microbiota revealed differences
      between TLR4DeltaIEC and wild-type mice, while meta-transcriptome analysis of the
      microbiota showed that intestinal TLR4 affected the expression of microbial genes
      involved in the metabolism of lipids, amino acids, and nucleotides. Genes
      regulated by peroxisome proliferator-activated receptors (PPARs) and the
      antimicrobial peptide lysozyme were significantly downregulated in TLR4DeltaIEC
      mice, suggesting a mechanism by which intestinal TLR4 could exert its effects on
      the microbiota and metabolic syndrome. Supportingly, antibiotics prevented both
      downregulation of PPAR genes and the development of metabolic syndrome, while
      PPAR agonists prevented development of metabolic syndrome in TLR4DeltaIEC mice.
      Thus, intestinal epithelial TLR4 regulates metabolic syndrome through altered
      host-bacterial signaling, suggesting that microbial or PPAR-based strategies
      might have therapeutic potential for this disease.

PMID- 29363673
TI  - Cytoskeleton in high resolution.

PMID- 29363674
TI  - Gene expression: AMPK relieves PRC2-mediated silencing.

PMID- 29363675
TI  - Transimplant antral lavage as minimally invasive treatment of chronic
      rhinosinusitis: Preliminary report of 11 consecutive cases.
AB  - OBJECTIVE: The present article reports how a dental implant with an internal port
      dental implant valve approach (DIVA) can be utilized as oroantral port to treat
      chronic rhinosinusitis (CRS) in a minimally invasive manner. METHOD AND
      MATERIALS: Eleven patients (age mean 68.1 years) with CRS were subjected to the
      transimplant lavage technique. For three patients the CRS treatment was performed
      via previously installed dental implants, and for another eight patients the
      implantation procedure was combined with the CRS treatment. The moment the
      implant was fully installed, the sinus membrane was punctured via the implant
      channel. Upon completion of the pus drainage the sinus was irrigated with normal
      saline, followed by the injection of a steroid solution (100 mg hydrocortisone).
      RESULTS: Patients began to report symptomatic improvement from the first day
      after the first-session procedure. Nine patients had complete relief of most of
      their symptoms (nasal obstruction/discharge, anosmia/hyposmia) at day 30. The
      follow- up nasal endoscopy demonstrated no evidence of active sinus disease. All
      the implants used were found to be well-osseointegrated and still in use for
      prosthetic purposes. Clinical and radiologic results showed stability and no
      recurrence in the follow-up period. CONCLUSION: The dental implant with an
      internal central port and integral dedicated sealing screw may be used for
      irrigation, observation, and further treatment of the maxillary sinus in cases of
      CRS.

PMID- 29363672
TI  - Once and only once: mechanisms of centriole duplication and their deregulation in
      disease.
AB  - Centrioles are conserved microtubule-based organelles that form the core of the
      centrosome and act as templates for the formation of cilia and flagella.
      Centrioles have important roles in most microtubule-related processes, including
      motility, cell division and cell signalling. To coordinate these diverse cellular
      processes, centriole number must be tightly controlled. In cycling cells, one new
      centriole is formed next to each pre-existing centriole in every cell cycle.
      Advances in imaging, proteomics, structural biology and genome editing have
      revealed new insights into centriole biogenesis, how centriole numbers are
      controlled and how alterations in these processes contribute to diseases such as
      cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the
      existence of surveillance pathways that limit the proliferation of cells with
      numerical centriole aberrations. Owing to this progress, we now have a better
      understanding of the molecular mechanisms governing centriole biogenesis, opening
      up new possibilities for targeting these pathways in the context of human
      disease.

PMID- 29363676
TI  - Diagnosis of aggressive periodontitis: A dilemma?
AB  - Periodontitis is one of the leading causes of tooth loss in the adult population.
      This disease can be classified into various categories, and one of the most
      destructive amongst them is aggressive periodontitis (AgP). The incidence of AgP
      is lower than other types of periodontitis. However, it affects young individuals
      and can cause severe destruction of tooth-supporting structures including tooth
      loss if left untreated. The current classification for diagnosing periodontal
      disease was established by the American Academy of Periodontology (AAP) in 1999.
      This classification provided strict guidelines to aid in AgP diagnosis. These
      include three main factors: systemically healthy individual, rapid loss of
      clinical attachment, and familial aggregation. In spite of these specific
      guidelines, AgP diagnosis is often missed clinically due to various reasons.
      There is still a vast variation in the diagnostic criteria for identifying AgP
      and not all practitioners utilize the AAP guidelines for their diagnosis.
      Furthermore, the definition of the disease might be changing in the future to
      better represent the current understanding of the disease. Since early diagnosis
      and prompt treatment is key in treating these patients, it is important to have
      calibration in the diagnosis process. This review aims to identify sources of
      variation and ambiguity in diagnosing AgP among dental practitioners. For this
      purpose, we have conducted an extensive literature search and outlined the
      various diagnostic aids for AgP patients reported in the literature.
      Understanding and correcting these variations can simplify the diagnostic process
      leading to faster treatment of patients affected with AgP. This review also
      emphasizes the importance of minimizing the bias in identifying patients with AgP
      and highlights the best tools for this purpose.

PMID- 29363677
TI  - Decoronation of an ankylosed tooth: Postoperative restoration by means of an
      intermediate fixed orthodontic laboratory device.
AB  - : Rehabilitation of missing decoronated permanent incisors in growing children
      and adolescents is a major challenge. The psychologic impact of the loss of an
      incisor is significant due to its immediate influence on facial appearance. Final
      restoration is planned only after skeletal growth cessation. Consequently, the
      fabrication and installation of an immediate temporary restoration, which is
      expected to remain in place for a long period, must meet the patient's esthetic
      demands and be durable in the oral environment. Several proposed removable and
      fixed restorations have presented significant shortcomings. The purpose of this
      report is to suggest a comfortable dental device for restoring the missing
      permanent tooth with improved esthetic, functional, and psychologic benefits. An
      alternative fixed orthodontic laboratory fabricated appliance for permanent tooth
      restoration is described among children with posttraumatic tooth decoronation.
      Unlike removable restorative appliances, this fixed device is not dependent on
      the child's compliance. Esthetically, no metal part is exposed in the anterior
      region and the architecture is more sturdy and stable, with minimum interruption
      to the alveolar ridge's vertical development. CASE REPORT: An alternative fixed
      orthodontic laboratory appliance is described for intermediate restoration of a
      missing permanent tooth. CLINICAL RELEVANCE: A posttrauma intermediate fixed
      orthodontic appliance is a beneficial solution from esthetic, psychologic,
      functional, and economic perspectives for replacing missing anterior maxillary
      teeth. This device may be worn by patients for a long period until final
      restoration is indicated.

PMID- 29363678
TI  - Effect of bone quality, implant design, and surgical technique on primary implant
      stability.
AB  - OBJECTIVE: Adaptation of the surgical protocol and implant selection depending on
      bone quality has been advocated. It was the goal of this in-vitro study to
      quantify the effect of implant geometry and implant site preparation on
      micromotion at the implant-bone interface. METHOD AND MATERIALS: A parametric
      study was conducted with implants differing in shape, length, and diameter placed
      in polyurethane foam material differing in density and structure following
      various methods of implant site preparation. Measurement parameters included bone
      quality in the cervical and apical area, insertion torque, implant stability, and
      implant displacement under load application. Statistical analysis was based on
      ANOVA and Pearson's product moment correlation with the level of significance set
      at alpha = .05. RESULTS: Compressive testing of bone allowed different bone
      densities (P = .000) to be distinguished. Minor changes in bone density caused by
      implant site preparation with osteotomes could not be detected (P > .05).
      Undersized drilling (P = .001), the presence of a cortical layer (P = .000), and
      the use of osteotomes (P = .000) led to a significant increase in implant
      insertion torque. Thread cutting reduced insertion torque (P = .000) whereas the
      use of short (P = 1.000) and wide diameter (P = .235) implants had no effect.
      Implant stability measurements did not always allow for differentiation of
      implants varying in shape and placed with different protocols. Increasing bone
      density led to a general reduction in maximum implant displacement under loading.
      Significant correlations between all parameters were found, with the exception of
      residual implant displacement, which only correlated with compressive bone
      testing in the cortical (P = .0341) and trabecular (P = .0359) areas. CONCLUSION:
      Compressive testing of bone seems to allow the prediction of implant performance.

PMID- 29363679
TI  - Cross-sectional study on the prevalence of carotid artery calcifications,
      tonsilloliths, calcified submandibular lymph nodes, sialoliths of the
      submandibular gland, and idiopathic osteosclerosis using digital panoramic
      radiography in a Lower Austrian subpopulation.
AB  - OBJECTIVE: Bone and soft tissue calcifications can often be visualized on
      panoramic radiographs, thus leading to presumptive diagnoses requiring further
      examinations. This cross-sectional study determined the prevalence of suspected
      carotid artery calcifications, tonsilloliths, calcified submandibular lymph
      nodes, sialoliths of the submandibular glands, and idiopathic osteosclerosis in a
      Lower Austrian subpopulation. METHOD AND MATERIALS: Digital panoramic radiographs
      (DPR) taken from 1,042 subjects for other clinical purposes between the years
      2013 and 2015 were evaluated, using a standardized template. Chi-square tests and
      Fisher's exact test were used to evaluate the relationship between the detected
      calcifications and patient age as well as sex. RESULTS: Radiographic data from
      490 men and 552 women (mean age of 49.2 [range 21 to 87] years) were analyzed.
      Two hundred and twenty calcifications were recorded in 198 subjects (19.0%), of
      which 100 (50.5%) were female. The mean age of participants with calcifications
      was 55.8 [SD 14.1] years. Radiopaque structures included carotid artery
      calcifications (5.7%), tonsilloliths (5.7%), calcified submandibular lymph nodes
      (3.6%), sialoliths of the submandibular gland (0.9%), and idiopathic
      osteosclerosis (5.3%) as presumptive diagnoses. In total, 196 calcifications
      (89.1%) were recorded in patients older than 40 years; no gender-dependent
      relationship could be revealed. Multiple calcification types were detected in 20
      patients (11 women, 9 men). CONCLUSIONS: With a prevalence of 19.0% in the study
      population, calcifications observed on DPR are more spread than previously
      reported. Thus, with patients of increasing age, DPR should be regarded as an
      important tool for basic screening of suspicious calcifications necessitating
      further diagnostic assessments.

PMID- 29363680
TI  - Assay of serum cholinesterase activity by an amperometric biosensor based on a co
      crosslinked choline oxidase/overoxidized polypyrrole bilayer.
AB  - Based on choline oxidase immobilized by co-crosslinking on an overoxidised
      polypyrrole modified platinum electrode, a novel electrochemical assay for
      cholinesterase activity in human serum was developed. The assay was performed by
      adding an aliquot of cholinesterase standard solution or serum sample to
      phosphate buffer containing choline or thiocholine ester and measuring the
      oxidation current of hydrogen peroxide at the rotating modified electrode
      polarized at +0.7 V vs. SCE. The influence of some experimental parameters such
      as pH of the assay, mass transport at the electrode, type and concentration of
      the cholinesterase substrate was studied and optimised. Reversible inhibition of
      choline oxidase from cholinesterase substrates was evidenced for the first time,
      which increases in the order of acetylcholine, butyrylcholine and s
      butyrylthiocholine. Wide linear range, fast response time and appreciable long
      term stability were assured for both acethyl- and butyrylcholinesterase assays.
      On allowing the polypyrrole layer to efficiently remove interferences from the
      electroactive compounds in the sample, the present method revealed to be suitable
      for the detection of butyrylcholinesterase in human serum at activities as low as
      0.5 U L-1. The validation with a reference spectrophotometric method showed no
      significant differences when human serum samples were analysed.

PMID- 29363681
TI  - Performance of point-of-care diagnosis of AIDS: label-free one-step-immunoassay
      vs. lateral flow assay.
AB  - The objective of this study is to develop an accurate, rapid, simple, and label
      free assay technology that enables point-of-care diagnosis of AIDS. For this, 3
      dimensional (3D) probes to sensitively detect anti-HIV antibodies were designed
      and synthesized by genetically presenting a HIV antigen (gp41) on the surface of
      engineered human ferritin nanoparticles. The 3D probes also present multi-copies
      of the hexa-histidine peptide (H6) on their surface to chemisorb gold ions
      (Au3+), which is essential for the generation and self-enhancement of assay
      signals. The developed new assay technology (named "one-step-immunoassay")
      quickly produced clear optical signals through a simple and convenient one-step
      procedure. The diagnostic performance of the one-step-immunoassay was compared
      with that of the conventional lateral flow assay (LFA) using 30 AIDS patient and
      20 healthy sera. The sensitivity of LFA was only 63% when a single antigen (gp41)
      was used but enhanced to 90% when three different antigens (gp41, p24, and gp120)
      were used together as the assay probes. In contrast, the one-step-immunoassay
      using only gp41 produced strong optical signals within 15 min without causing any
      false negative/positive signals, showing 100% sensitivity and 100% specificity
      and holding promising potential for clinical point-of-care diagnosis of AIDS.

PMID- 29363682
TI  - Therapeutic applications of iron oxide based nanoparticles in cancer: basic
      concepts and recent advances.
AB  - Nanotechnology has introduced new techniques and phototherapy approaches to
      fabricate and utilize nanoparticles for cancer therapy. These phototherapy
      approaches, such as photothermal therapy (PTT) and photodynamic therapy (PDT),
      hold great promise to overcome the limitations of traditional treatment methods.
      In phototherapy, magnetic iron oxide nanoparticles (IONPs) are of paramount
      importance due to their wide range of biomedical applications. This review
      discusses the basic concepts, various therapy approaches (PTT, PDT, magnetic
      hyperthermia therapy (MHT), chemotherapy and immunotherapy), intrinsic
      properties, and mechanisms of cell death of IONPs; it also provides a brief
      overview of recent developments in IONPs, with focus on their therapeutic
      applications. Much attention is devoted to elaborating the various parameters,
      intracellular behaviors and limitations of MHT. Bimodal therapies which act alone
      or in combination with other modalities are also discussed. The review highlights
      some limitations in the explored research areas and suggests future directions to
      overcome these limitations.

PMID- 29363683
TI  - Naphthalimide derivatives as multifunctional molecules for detecting 5
      formylpyrimidine by both PAGE analysis and dot-blot assays.
AB  - An azide and hydrazine tethered to a naphthalimide analogue was created to
      selectively react with 5-formyluracil in one system and fluorogenically label 5
      formylcytosine in another system. A biotin group was also introduced by copper
      free click chemistry through selective labelling of the aldehyde present in 5
      formylpyrimidine.

PMID- 29363684
TI  - Metal-mediated linear self-assembly of porphyrins.
AB  - Porphyrin derivatives are highly relevant to biological processes such as light
      harvesting and charge separation. Their aromatic electronic structure and their
      accessible HOMO-LUMO gap render porphyrins highly attractive for the development
      of opto- and electro-active materials. Due to the often difficult covalent
      synthesis of multiporphyrins, self-assembly using metal complexation as the
      driving force can lead to well defined objects exhibiting a controlled
      morphology, which will be required to analyse and understand the electronic
      properties of porphyrin wires. This article presents two assembly approaches,
      namely by peripheral coordination or by binding to a metal ion in the porphyrin
      core, that are efficient and well designed for future developments requiring
      interactions with a surface.

PMID- 29363685
TI  - Nonthermal optical emission spectrometry for simultaneous and direct
      determination of zinc, cadmium and mercury in spray.
AB  - A nonthermal optical emission spectrometric (OES) system is developed for the
      simultaneous multi-element determination of zinc, cadmium and mercury, with a
      dielectric barrier discharge (DBD) microplasma generated on the nozzle of a
      pneumatic micronebulizer as the excitation source. After solution nebulization,
      zinc, cadmium and mercury are directly atomized and excited in the spray by a DBD
      microplasma for performing optical emission. The emission spectra are measured
      with a charge-coupled device (CCD) spectrometer. Various important parameters
      governing the analytical performance of the nonthermal OES system are
      scrutinized, encompassing the conditions of sample solution introduction,
      microplasma formation, signal collection and matrix matching for DBD-OES
      detection. With the characteristic emission lines of Zn 213.9 nm, Cd 228.8 nm and
      Hg 253.7 nm as the analytical lines for quantification, the detection limits for
      the simultaneous determination of Zn, Cd and Hg are 22, 1.6, and 10 MUg L-1,
      respectively, and the corresponding linear ranges are 70-6000, 5-1000, and 35
      2000 MUg L-1, respectively. The accuracy of the present nonthermal OES system is
      confirmed by the determination of Zn, Cd and Hg in two certified reference
      materials, i.e., CRM 176 (city waste incineration ash) and GBW 08608 (water). The
      proposed nonthermal OES system provides a portable instrument for field analysis
      in emergency with low cost and low consumption.

PMID- 29363686
TI  - A flexible polyaniline-based bioelectronic patch.
AB  - Bioelectronic materials based on conjugated polymers are being developed in the
      hope to interface with electroresponsive tissues. We have recently demonstrated
      that a polyaniline chitosan patch can efficiently electro-couple with cardiac
      tissue modulating its electrophysiology. As a promising bioelectronic material
      that can be tailored to different types of devices, we investigate here the
      impact of varying the synthesis conditions and time of the in situ polymerization
      of aniline (An) on the sheet resistance of the bioelectronic patch. The sheet
      resistance increases significantly for samples that have either the lowest molar
      ratio of oxidant to monomer or the highest molar ratio of dopant to monomer,
      while the polymerization time does not have a significant effect on the
      electrical properties. Conductive atomic force microscopy reveals that the patch
      with the lowest sheet resistance has a connected network of the conductive phase.
      In contrast, patches with higher sheet resistances exhibit conductive areas of
      lower current signals or isolated conductive islands of high current signals.
      Having identified the formulation that results in patches with optimal electrical
      properties, we used it to fabricate patches that were implanted in rats for two
      weeks. It is shown that the patch retains an electroactive nature, and only mild
      inflammation is observed with fibrous tissue encapsulating the patch.

PMID- 29363687
TI  - Time-resolved visual detection of heparin by accelerated etching of gold
      nanorods.
AB  - Plasmonic gold nanorods are promising and sensitive light scattering probes,
      which can reach the single particle level. Herein, we present the light
      scattering properties of gold nanorods for time-resolved visual detection of
      heparin based on the rapid etching of gold nanorods under dark-field microscopy.

PMID- 29363688
TI  - Palladium-unleashed proteins: gentle aldehyde decaging for site-selective protein
      modification.
AB  - Protein bioconjugation frequently makes use of aldehydes as reactive handles,
      with methods for their installation being highly valued. Here a new, powerful
      strategy to unmask a reactive protein aldehyde is presented. A genetically
      encoded caged glyoxyl aldehyde, situated in solvent-accessible locations, can be
      rapidly decaged through treatment with just one equivalent of allylpalladium(ii)
      chloride dimer at physiological pH. The protein aldehyde can undergo subsequent
      oxime ligation for site-selective protein modification. Quick yet mild
      conditions, orthogonality and powerful exposed reactivity make this strategy of
      great potential in protein modification.

PMID- 29363689
TI  - Green synthesis and evaluation of an iron-based metal-organic framework MIL-88B
      for efficient decontamination of arsenate from water.
AB  - Iron-containing metal-organic frameworks (MOFs) have gradually emerged as
      environmentally benign alternatives for reducing the levels of environmental
      contamination because of their advantages, such as readily obtained raw materials
      with low cost, nontoxic metal source with good biocompatibility, and
      distinguished physicochemical features e.g., high porosity, framework
      flexibility, and semiconductor properties. In this study, we reported an
      innovative strategy for synthesizing an iron-based MOF, MIL-88B, at room
      temperature. The novelty of this strategy was the use of ethanol as solvent and
      the pretreatment of dry milling with neither the bulk use of a toxic organic
      solvent nor the addition of extremely dangerous hydrofluoric acid or strong
      alkali. The synthesized MIL-88B(Fe) was evaluated as a sorbent for removing
      arsenate in water and it exhibited high adsorption capacity (156.7 mg g-1) at a
      low dosage. The removal capacity of trace arsenate on MIL-88B(Fe) was 32.3 mg g-1
      at a low equilibrium concentration (6.4 MUg L-1), which satisfied the arsenic
      threshold for drinking water. The results of Fourier transform infrared and X-ray
      photoelectron spectroscopy indicated that the As(v) molecules bonded with the
      oxygen molecules, which were coordinated with FeO clusters in the framework. This
      work presented the potential use of the up-scaled MIL-88B as an excellent sorbent
      for purifying arsenate-contaminated water.

PMID- 29363690
TI  - New complex phosphates Cs3MIIBi(P2O7)2 (MII - Ca, Sr and Pb): synthesis,
      characterization, crystal and electronic structure.
AB  - Herein, the peculiarities of complex phosphate formation in self-fluxes of Cs-MII
      Bi-P-O (MII = Ca, Sr, Ba and Pb) systems with Cs/P = 0.7-1.3 at fixed ratios of
      Bi/P = 0.2 and Bi/MII = 1.0 were studied and discussed. Three novel isostructural
      diphosphates with the general composition Cs3MIIBi(P2O7)2 (MII = Ca, Sr and Pb)
      and the original framework topology were synthesized and characterized via single
      crystal and powder X-ray diffraction, SEM, DTA, and FTIR- and UV-VIS
      spectroscopy. In addition, electronic structure (DFT) and Voronoi-Dirichlet
      polyhedra (VDP) characteristics calculations and crystallochemical analysis were
      performed. In the structure of the new compounds, the MIIO7 and BiO6 polyhedra
      are connected via common oxygen vertices forming infinite helical-like chains,
      which are linked by P2O7 groups into a 3D-framework with pentagonal tunnels,
      where the Cs+ cations are located. The structural peculiarities are discussed
      considering perspectives for the creation of new luminescent materials. The
      dielectric bandgaps, Eg, of the Cs3MIIBi(P2O7)2 crystals reveal an ~0.2 eV low
      energy shift in the Ca-Sr-Pb sequence of MII cations, which reveals the
      possibility to tune the optical absorbance spectra of the crystals via the
      synthesis of solid solutions with various contents of MII cations. The glass
      ceramic synthetic approach is also proposed as a convenient method for the
      creation of new diphosphates, and the applicability of this method is verified
      for Cs3CaBi(P2O7)2.

PMID- 29363691
TI  - Photochromism in oxalatoniobates.
AB  - Addition of 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen) or 2-aminopyridine
      (2-NH2-py) to aqueous solutions of (NH4)[NbO(C2O4)2(H2O)2].3H2O (Nb-Ox) yields
      tris-oxalate complexes (bpyH2)(bpyH)[NbO(C2O4)3].2H2O (1),
      (phenH)3[NbO(C2O4)3].3H2O (2), and (2-NH2-pyH)3[NbO(C2O4)3].2H2O (3), which were
      characterised by XRD, IR and EA. Bipyridinium salt 1 demonstrates remarkable
      photoactivity even under irradiation by daylight. The nature of the photoactivity
      was studied by diffuse reflectance (DR) spectroscopy, ESR and quantum-chemical
      calculations.

PMID- 29363692
TI  - Host-guest capability of a three-dimensional heterometallic macrocycle.
AB  - A three-dimensional heterometallic coordination macrocycle is found to be capable
      of encapsulating planar pyrene (G1), coronene (G4) and non-planar corannulene
      (G2) guest molecules in high yields, giving rise to 1 : 1 host-guest complexes.
      The bowl-shaped guest corannulene is found to be significantly flattened upon
      inclusion within the cavity. However, macrocyclic compounds with larger cavity
      sizes, which form 1 : 1 stoichiometry assemblies with a naphthalene bisimide
      planar molecule (G3), are more inclined to form infinite sandwich structures.
      Furthermore, these heterometallic coordination macrocycles can be destroyed in
      the presence of a soft base to form hexanuclear triangular prism complexes. These
      structures are unambiguously revealed by single-crystal X-ray analysis.

PMID- 29363693
TI  - Concentration dependent supramolecular interconversions of triptycene-based
      cubic, prismatic, and tetrahedral structures.
AB  - The quantitative, single step, self-assembly of a shape-persistent, three
      dimensional C3v-symmetric, triptycene-based tris-terpyridinyl ligand initially
      gives a platonic-based cubic architecture, which was unequivocally characterized
      by 1D and 2D NMR spectroscopy, mass spectrometry, and single crystal X-ray
      structural analysis. The unique metal-ligand binding properties of the Cd2+
      analogue of this construct give rise to a concentration-dependent dynamic
      equilibrium between cube, prism, and tetrahedron-shaped architectures. Dilution
      transforms this cube into two identical tetrahedra through a stable prism-shaped
      intermediate; increasing the concentration reverses the process.

PMID- 29363694
TI  - Metal-organic frameworks based on octafluorobiphenyl-4,4'-dicarboxylate:
      synthesis, crystal structure, and surface functionality.
AB  - In contrast to aromatic carboxylates, the coordination polymers based on their
      perfluorinated analogues are not numerous. Here we present a series of six Zn(ii)
      coordination polymers of different dimensionalities (1D, 2D, and 3D) and
      porosities based on octafluorobiphenyl-4,4'-dicarboxylate (oFBPDC2-) and N
      containing co-ligands (ur, dabco, and bpy). These complexes are characterized by
      single-crystal X-ray diffraction, PXRD, FT-IR, elemental analysis, and TGA. The
      metal-organic frameworks [Zn2(CH3CONH2)2(oFBPDC)2] (1) and [Zn2(oFBPDC)2(dabco)]
      (4) are shown to be porous with BET surface areas of 470 m2 g-1 and 441 m2 g-1,
      respectively. In addition, compound 4 shows selectivity factors of 11.3, 4.9 and
      more than 6 for the binary gas mixtures CO2/N2, CO2/CH4 and benzene/cyclohexane,
      respectively. The measurements for pressed powders and water droplet give water
      contact angles of 136 degrees  for 4 and 133 degrees  for
      (H2bpy)[Zn2(bpy)(oFBPDC)3] (5). Low water uptake indicates that both 4 and 5
      belong to highly hydrophobic solids.

PMID- 29363695
TI  - A new BODIPY-derived ratiometric senor with internal charge transfer (ICT)
      effect: colorimetric/fluorometric sensing of Ag.
AB  - With a 4-aminostyryl group introduced at its 3-position, a BODIPY BDP-ODTAC was
      derived as a new ratiometric sensor for Ag+ by modifying 4-amino group as a Ag+
      chelator, 1-oxa-4,10-dithia-7-azacyclododecane (ODTAC). In addition to the
      specific Ag+-induced hypsochromic absorption shift from 606 to 562 nm, this
      sensor demonstrated an excitation shift from 600 to 560 nm due to the internal
      charge transfer (ICT) effect endowed by the introduced alpha-4-aminostyryl group.
      The Ag+-induced recovery and enhancement of the intrinsic local emission band was
      also observed. The different sensing behavior of ODTAC-BDP with chelator ODTAC
      substituting on the meso-phenyl group infers that the ratiometric sensing
      behavior of BDP-ODTAC is correlated to the amino group in ODTAC acting as the
      electron donor for the ICT effect. With high Ag+ selectivity over interfering
      cations such as Hg2+ and Pb2+, BDP-ODTAC displays a fluorometric limit of
      detection (LOD) of ~17 nM (~0.002 ppm), which is distinctly lower than EPA and
      WHO standards for drinking water (500 nM, ~0.055 ppm). Moreover, the BDP-ODTAC
      doped PVC film shows the Ag+ sensitivity of 1 ppm with a color switch from blue
      to purple, providing this sensor the ability to determine Ag+ in totally aqueous
      solution sensitively via naked-eye detection.

PMID- 29363696
TI  - Catalytic N-Si coupling as a vehicle for silane dehydrocoupling via alpha
      silylene elimination.
AB  - Exploration of (N3N)ZrNMe2 (1, N3N = N(CH2CH2NSiMe3)33-) as a catalyst for the
      cross-dehydrocoupling or heterodehydrocoupling of silanes and amines suggested
      silylene reactivity. Further studies of the catalysis and stoichiometric modeling
      reactions hint at alpha-silylene elimination as the pivotal mechanistic step,
      which expands the 3p elements known to engage in this catalysis and provides a
      new strategy for the catalytic generation of low-valent fragments.

PMID- 29363697
TI  - A yolk-shell V2O5 structure assembled from ultrathin nanosheets and coralline
      shaped carbon as advanced electrodes for a high-performance asymmetric
      supercapacitor.
AB  - Various V2O5 three-dimensional nanostructures are synthesized using a facile
      template-free hydrothermal method and evaluated for use as supercapacitor
      electrode materials. As a result, the yolk-shell structure assembled from
      ultrathin nanosheets shows the best electrochemical performance, with a specific
      capacitance of 704.17 F g-1 at 1.0 A g-1 and a high capacity retention of 89%
      over 4000 cycles at 3.0 A g-1. In addition, a continuous three-dimensional porous
      coralline-shaped carbon is synthesized from osmanthus and has a large Brunauer
      Emmett-Teller surface area of 2840.88 m2 g-1. Then, an asymmetric supercapacitor
      is developed using the as-prepared yolk-shell V2O5 as a positive electrode and
      the osmanthus derived coralline-shaped carbon as a negative electrode. This
      exhibits an energy density of 29.49 W h kg-1 at a power density of 800 W kg-1
      with a good cycling performance that retains 90.6% of its initial capacity after
      2000 cycles at 3.0 A g-1. Furthermore, two cells in series can easily brightly
      light up a light-emitting diode (3 V), further demonstrating the great potential
      of the prepared materials for high-performance supercapacitor devices.

PMID- 29363698
TI  - Modifying the donor properties of tris(pyridyl)aluminates in lanthanide(ii)
      sandwich compounds.
AB  - The coordination ability of tris(pyridyl)aluminates can be modified by the steric
      and electronic character of substituents at the 6-positions of their pyridyl
      rings. Whereas [EtAl(6-Me-2-py)3]- (1) coordinates strongly to lanthanide(ii)
      ions [Eu(ii) and Yb(ii)], [EtAl(6-Br-2-py)3]- (2) forms much weaker complexes,
      and [EtAl(6-CF3-2-py)3]- does not coordinate at all. The modification of the
      donor ability of these ligands is investigated by solid-state studies of the
      Ln(ii) sandwich compounds and by competitive coordination studies in solution.

PMID- 29363699
TI  - Hierarchical 3D NiFe2O4@MnO2 core-shell nanosheet arrays on Ni foam for high
      performance asymmetric supercapacitors.
AB  - Hierarchical NiFe2O4@MnO2 core-shell nanosheet arrays (NSAs) were synthesized on
      Ni foam as an integrated electrode for supercapacitors, using a facile two-step
      hydrothermal method followed by calcination treatment. The NiFe2O4 nanosheets
      were designed as the core and ultrathin MnO2 nanoflakes as the shell, creating a
      unique three-dimensional (3D) hierarchical electrode on Ni foam. The composite
      electrode exhibited remarkable electrochemical performance with a high specific
      capacitance of 1391 F g-1 at a current density of 2 mA cm-2 and long cycling
      stability at a high current density of 10 mA cm-2 (only 11.4% loss after 3000
      cycles). Additionally, an asymmetric supercapacitor (ASC) device was fabricated
      with a NiFe2O4@MnO2 composite as the positive electrode material and activated
      carbon (AC) as the negative one. The ASC device exhibited a high energy density
      (45.2 W h kg-1) at a power density of 174 W kg-1, and an excellent cycling
      stability over 3000 cycles with 92.5% capacitance retention. The remarkable
      electrochemical performance demonstrated its great potential as a promising
      candidate for high-performance supercapacitors.

PMID- 29363700
TI  - Optically sensing phospholipid induced coil-helix transitions in the
      phosphoinositide-binding motif of gelsolin.
AB  - We present a systematic experimental and computational study of phospholipid
      induced peptide coil-helix transitions which are relevant in the context of
      proteins mediating cytoskeletal rearrangement via membrane binding. We developed
      a sensitive Forster resonance energy transfer (FRET) based assay to address
      whether coil-helix transitions in phospholipid binding motifs of actin-binding
      proteins can be induced by physiologically-relevant concentrations (1-20 MUM) of
      phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) phospholipids. Based on inter
      residue distance constraints obtained from Molecular Dynamics (MD) simulations of
      a 20 residue peptide (Gel 150-169) from the actin-severing protein gelsolin, we
      synthetized and labeled the peptide with a tryptophan donor and IAEDANS acceptor
      pair. Upon addition of PI(4,5)P2 micelles and mixed vesicles containing PI(4,5)P2
      and phosphatidylcholine to the peptide, we observed a decrease in the tryptophan
      emission intensity with increasing concentrations of PI(4,5)P2. The IAEDANS
      emission spectra showed a more complex profile exhibiting a blue shift of the
      emission peak and non-monotonic changes in the intensity profile with increasing
      concentrations of PI(4,5)P2. We showed that the IAEDANS acceptor emission
      response is a result of both intrinsic polarity sensitivity of the acceptor in
      the vicinity of the membrane surface and fluorescence energy transfer from the
      donor. Importantly, the fluorescence lifetime of the donor (tryptophan) showed a
      monotonous decrease with increasing mol% of PI(4,5)P2 from 1.13 +/- 0.10 ns in
      the absence of phospholipids to 0.25 +/- 0.03 ns in the presence of 100%
      PI(4,5)P2 micelles. We also showed a concomitant increase in FRET efficiency with
      increasing PI(4,5)P2 levels indicating a PI(4,5)P2 concentration dependent coil
      helix transition. Our studies demonstrate that membrane PI(4,5)P2 concentrations
      as low as 2.5-5 MUM can trigger helix-coil conformational changes in gelsolin
      relevant for triggering regulatory processes in the cell.

PMID- 29363704
TI  - Quantitative N-glycoproteomics of milk fat globule membrane in human colostrum
      and mature milk reveals changes in protein glycosylation during lactation.
AB  - Milk fat globule membrane (MFGM) proteins have recently gained increasing
      attention, due to their significant biological function. However, the
      glycosylation of proteins in human MFGM during lactation has not been studied in
      detail. In this study, through mass spectroscopy-based N-glycoproteomics, we
      analyzed protein glycosylation of human MFGM. A total of 912 N-glycosylation
      sites on 506 N-glycoproteins were identified in human colostrum and mature milk
      MFGM. Among them, 220 N-glycoproteins with 304 N-glycosylation sites were
      differentially expressed in colostrum and mature milk MFGM. Gene Ontology (GO)
      analysis revealed various biological processes, cellular components, and
      molecular functions of the differentially expressed N-glycoproteins.
      Specifically, these glycoproteins were involved in biological processes such as
      single-organism processes, biological regulation, regulation of biological
      processes, response to stimulus and localization; were cellular components in
      organelles, membranes, and the extracellular region; and had different molecular
      functions such as protein binding, receptor activity, and hydrolase activity.
      KEGG pathway analysis suggested that the majority of the differentially expressed
      N-glycoproteins were associated with phagosome, cell adhesion molecule and some
      disease-related pathways. Our results provide an in-depth understanding of the
      quantitative changes in N-glycosylation of proteins in human colostrum and mature
      MFGM, and extend our knowledge of the N-glycoproteome and of the distribution of
      N-glycosylation sites in human MFGM during lactation, providing insight into the
      biological functions of the highlighted glycoproteins.

PMID- 29363708
TI  - DBU-promoted carbonylative synthesis of 1,3-oxathiolan-2-ones from propargylic
      alcohols with TFBen as the CO source.
AB  - A DBU-promoted carbonylative cyclization of propargylic alcohols with sulfur was
      developed. Various 1,3-oxathiolan-2-ones were produced in 61-98% yields under
      mild conditions in the absence of metal catalysts. TFBen (benzene-1,3,5-triyl
      triformate) as an efficient and solid CO surrogate and S8 as an ideal sulfur
      source were employed and incorporated.

PMID- 29363709
TI  - Stretching and compression of DNA by external forces under nanochannel
      confinement.
AB  - Mechanical deformation of dsDNA molecules inside square nanochannels is
      investigated using simulations based on a coarse-grained model of DNA. The
      combined action of confinement and weak external forces is explored in a variety
      of confinement regimes, including the transition zone relevant to nanofluidic
      experiments. The computed free energy and force profiles are markedly affected by
      the channel size. Effective elastic softening of confined DNA molecules relative
      to the bulk DNA is observed in the channels of intermediate widths. The extension
      of DNA from its bulk equilibrium length in nanofluidic devices is resolved into
      contributions from the passive extension due to confinement and from the active
      stretching induced by force. Potential implications of the very different energy
      costs computed for the two extension modes (extension by confinement takes much
      more free energy than stretching by force) for behavior of DNA in nanofluidic
      chips are indicated.

PMID- 29363710
TI  - Anti-Alzheimers activity and molecular mechanism of albumin-derived peptides
      against AChE and BChE.
AB  - Alzheimer's disease (AD) is a global health issue affecting millions of elderly
      people worldwide. The aim of the present study was to identify novel anti-AD
      peptides isolated from albumin. Anti-AD activities of the peptides were evaluated
      via inhibitory activities on acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE). Furthermore, the potential molecular mechanisms of
      the KLPGF/AChE were investigated by CDOCKER of Discovery studio 2017. The results
      revealed that peptide KLPGF could effectively inhibit AChE with an inhibition
      rate of 61.23% at a concentration of 50 MUg mL-1. In addition, the peptide KLPGF
      came in contact with acylation sites and peripheral anion sites of AChE. The
      present study demonstrates that the peptide KLPGF could become a potential
      functional food intervention in AD.

PMID- 29363714
TI  - Prediction of long-term absence due to sickness in employees: development and
      validation of a multifactorial risk score in two cohort studies.
AB  - Objectives This study aimed to develop and validate a risk prediction model for
      long-term sickness absence. Methods Survey responses on work- and lifestyle
      related questions from 65 775 public-sector employees were linked to sickness
      absence records to develop a prediction score for medically-certified sickness
      absence lasting >9 days and >=90 days. The score was externally validated using
      data from an independent population-based cohort of 13 527 employees. For both
      sickness absence outcomes, a full model including 46 candidate predictors was
      reduced to a parsimonious model using least-absolute-shrinkage-and-selection
      operator (LASSO) regression. Predictive performance of the model was evaluated
      using C-index and calibration plots. Results Variance explained in >=90-day
      sickness absence by the full model was 12.5%. In the parsimonious model, the
      predictors included self-rated health (linear and quadratic term), depression,
      sex, age (linear and quadratic), socioeconomic position, previous sickness
      absences, number of chronic diseases, smoking, shift work, working night shift,
      and quadratic terms for body mass index and Jenkins sleep scale. The
      discriminative ability of the score was good (C-index 0.74 in internal and 0.73
      in external validation). Calibration plots confirmed high correspondence between
      the predicted and observed risk. In >9-day sickness absence, the full model
      explained 15.2% of the variance explained, but the C-index of the parsimonious
      model was poor (<0.65). Conclusions Individuals' risk of a long-term sickness
      absence that lasts >=90 days can be estimated using a brief risk score. The
      predictive performance of this score is comparable to those for established
      multifactorial risk algorithms for cardiovascular disease, such as the Framingham
      risk score.

PMID- 29363715
TI  - Early Relief of Pruritus in Atopic Dermatitis with Crisaborole Ointment, A Non
      steroidal, Phosphodiesterase 4 Inhibitor.
AB  - Pruritus occurs in all patients with atopic dermatitis and requires quick relief
      to reduce disease exacerbation and improve quality of life. Crisaborole ointment
      is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild-to
      moderate atopic dermatitis. This post hoc analysis explores crisaborole ointment
      for early relief of pruritus in patients with mild to moderate atopic dermatitis
      from 2 phase III studies. Patients received crisaborole or vehicle twice daily
      for 28 days. Pruritus was graded on a 4-point scale of none (0) to severe (3).
      Early improvement in pruritus required a score of none (0) or mild (1), with a >=
      1-grade improvement from baseline on day 6. Significantly more patients
      experienced early improvement in pruritus with crisaborole than with vehicle
      (56.6% vs 39.5%; p< 0.001), including at earliest assessment (day 2, 34.3% vs
      27.3%; p = 0.013). Crisaborole is a topical treatment option that can rapidly
      relieve atopic dermatitis-associated pruritus.

PMID- 29363716
TI  - Apoptosis induced by methanol extract of Potentilla discolor in human
      mucoepidermoid carcinoma cells through STAT3/PUMA signaling axis.
AB  - Potentilla discolor has been used in traditional Chinese medicine for the
      treatment of hyperglycemia. However, the potential role of Potentilla discolor
      against cancer and its mode of action remain to be fully elucidated. The present
      study explored the apoptotic effect of methanol extract of Potentilla discolor
      (MEPD) in human mucoepidermoid carcinoma (MEC) cell lines of salivary glands.
      MEPD markedly suppressed the growth and induced apoptotic cell death in MC3 and
      YD15 cells. MEPD treatment significantly upregulated the expression of PUMA and
      reduced STAT3 phosphorylation. Overexpression of STAT3 partially recovered the
      growth of MEC cells inhibited by MEPD. In addition, dephosphorylation of STAT3 by
      cryptotanshinone (a potent STAT3 inhibitor) was sufficient to inhibit the growth
      of MEC cells and induce apoptosis via affecting PUMA protein. These results
      suggest that MEPD has a potential anticancer property via the STAT3/PUMA
      signaling axis in human MEC cells of salivary gland.

PMID- 29363717
TI  - Inhibition of microRNA-19b promotes ovarian granulosa cell proliferation by
      targeting IGF-1 in polycystic ovary syndrome.
AB  - The purpose of the present study was to investigate the functional role of
      microRNA (miR)-19b in polycystic ovary syndrome (PCOS) and try to elucidate its
      underlying mechanisms. Expression of miR-19b and insulin-like growth factor 1
      (IGF-1) was examined in ovarian cortexes [(from 18 women with PCOS and 10 who did
      not have PCOS (non-PCOS)] and KGN cells. Cell proliferation assays (cell
      viability and colony formation assay) were performed following overexpression or
      inhibition of miR-19b and IGF-1 or following insulin treatment in KGN cells.
      Expression levels of the cell cycle-associated protein cyclin D1 and cyclin
      dependent kinase (CDK) 1 were analyzed following overexpression or inhibition of
      miR-19b and IGF-1. Potential miR-19b targets were identified by bioinformatics.
      Luciferase assay, reverse transcription-quantitative polymerase chain reaction
      and western blotting were performed to determine whether IGF-1 was a target of
      miR-19b. miR-19b expression was significantly decreased in the PCOS ovarian
      cortex and KGN cells and its identified target, IGF-1, was upregulated. miR-19b
      overexpression inhibited cell proliferation at G2/M phrase. Overexpression of IGF
      1 promoted cell viability and colony formation ability in KGN cells. The
      expression of cyclin D1 and CDK1 was statistically increased by inhibition of miR
      19b and overexpression of IGF-1. High concentrations of insulin decreased levels
      of miR-19b, stimulated KGN cell proliferation, and elevated IGF-1 levels.
      Inhibition of miR-19b promoted ovarian granulosa cell proliferation by targeting
      IGF-1 in PCOS. Insulin decreased the expression levels of miR-19b and stimulated
      cell proliferation. The present study suggested that overexpression of miR-19b
      may be a potential therapeutic approach for PCOS.

PMID- 29363718
TI  - Human placenta mesenchymal stem cells suppress airway inflammation in asthmatic
      rats by modulating Notch signaling.
AB  - Neurogenic locus notch homolog protein (Notch) signaling mediates intracellular
      communication and may regulate cell fate decisions, including cell proliferation,
      differentiation, and apoptosis. Mesenchymal stem cells (MSCs) possess
      immunomodulatory properties and the potential for use in stem cell replacement
      treatments. The aim of the present study was to evaluate the therapeutic effects
      of human placenta-deviated MSCs (hPMSCs) in asthma and to investigate the
      mechanisms of Notch signaling mediated by transplanted MSCs. A Sprague-Dawley rat
      ovalbumin (OVA)-sensitized acute asthma model was established and challenged.
      MSCs derived from human placenta (hPMSCs) were transplanted into the asthmatic
      rats. Transplantation resulted in reduced Notch-1, Notch-2 and jagged-1, and
      increased Notch-3, Notch-4 and delta-like ligand (delta)-4 expression in lung,
      blood, and lymph samples. Notch-1, Notch-2, and jagged-1 expression in OVA
      treated rats was significantly decreased compared with controls and hPMSC-treated
      rats; however, Notch-3, Notch-4 and delta-4 expression was significantly
      increased. Serum interferon-gamma significantly increased after hPMSCs
      transplantation, whereas interleukin-4 and immunoglobulin E decreased. In OVA
      treated rats, Notch-1, Notch-2 and jagged-1 levels were increased in the lymph
      compared with the blood, although Notch-4 and delta-4 levels were decreased.
      Peribronchial infiltration of cells and goblet cell hyperplasia were markedly
      decreased in the OVA + hPMSCs group compared with those in the OVA-treated and
      control groups. Alterations in Notch signaling pathway expression were
      accompanied by decreased inflammatory cell infiltration, goblet cell hyperplasia
      and mucus production in lung tissues. The results of the present study are
      consistent with hPMSC suppression of asthma symptoms and inflammation by
      regulating the Notch signaling pathway in the rat asthma model.

PMID- 29363719
TI  - miR-483-3p regulates acute myocardial infarction by transcriptionally repressing
      insulin growth factor 1 expression.
AB  - The aim of the present study was to evaluate the functional association between
      the expression of miR-483-3p and acute myocardial infarction (AMI) in patients
      and in vitro. H9c2 cells were incubated in a vacuum with 5% CO2, 5% H2 and 90% N2
      for 2 h, which generated the AMI model in vitro. Reverse transcription
      quantitative polymerase chain reaction was used to measure miR-483-3p expression,
      and flow cytometry analysis and ELISA analysis were used to analyze apoptosis
      rate via caspase-3 and caspase-9 activity kits. B-cell lymphoma 2 (Bcl-2)/Bcl-2
      associated X protein (Bax) and transcriptionally suppressed the protein
      expression of insulin growth factor 1 (IGF-1) were analyze using western blot
      analysis. The results demonstrated that the expression of miR-483-3p in patients
      with AMI was increased when compared with the control group. In the in vitro
      model, the overexpression of miR-483-3p promoted apoptosis, increased caspase-3
      and caspase-9 activity levels, induced the protein expression of Bcl-2/Bax and
      IGF-1. Picropodophyllotoxin, an IGF-1 inhibitor, was administered to cells
      following the overexpression of miR-483-3p. Administration of
      picropodophyllotoxin suppressed IGF-1 protein expression, promoted apoptosis,
      increased caspase-3 and caspase-9 activity levels, and induced the protein
      expression of Bax/Bcl-2. The results of the present study revealed that miR-483
      3p may regulate AMI via the IGF-1 signaling pathway and may support the
      restoration of functional performance following AMI.

PMID- 29363720
TI  - Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA
      126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway.
AB  - Tubeimoside-1 (TBMS1), a triterpenoid saponin isolated from the tuber of
      Bolbostemma paniculatum (Maxim) Franquet, serves an universal suppressive role in
      multiple cancer types, including lung cancer. However, the mechanism involved in
      non-small cell lung cancer (NSCLC) cells by which TBMS1 elicits its antitumor
      effects is not yet comple-tely understood. The present study indicated that 10
      umol/l TBMS1 significantly enhanced apoptosis and notably blocked the migration
      and invasion of NCI-H1299 cells. These effects were reversed following
      transfection with miR-126-5p inhi-bitor into TBMS1-treated NCI-H1299 cells.
      Vascular endo-thelial growth factor-A (VEGF-A) is a target gene for miR-126-5p.
      Notably, results suggested that the downregulated VEGF-A and VEGFR-2 in TBMS1
      treated NCI-H1299 cells were upregulated after inhibiting miR-126-5p, and
      overexpression of VEGF-A or VEGFR-2 could significantly reduce apoptosis and
      promote the migration and invasion of TBMS1-treated NCI-H1299 cells. Furthermore,
      TBMS1 combined with TBHQ (an ERK activator) dramatically suppressed TBMS1-induced
      apoptosis and stimulated TBMS1-reduced migration and invasion in NCI-H1299 cells,
      suggesting that TBMS1 inhibits the ERK signaling pathway and represses the growth
      and metastasis of NCI-H1299 cells. Further study demonstrated that either
      inhibiting miR-126-5p or overexpressing VEGF-A and VEGFR-2 in TBMS1-treated NCI
      H1299 cells elevated the mRNA expression levels and phosphorylation levels of
      MEK1, as well as ERK. To conclude, TBMS1 increases miR-126-5p expression, whereas
      overexpressing miR-126-5p inactivates VEGF-A/VEGFR-2/ERK signaling pathway, which
      ultimately actuates the pro-apoptotic and anti-metastatic effects in NCI-H1299
      cells. Therefore, the present findings provide a theoretical foundation for TBMS1
      as a potential candidate in NSCLC treatment.

PMID- 29363721
TI  - Paeoniflorin induces G2/M cell cycle arrest and caspase-dependent apoptosis
      through the upregulation of Bcl-2 X-associated protein and downregulation of B
      cell lymphoma 2 in human osteosarcoma cells.
AB  - Paeoniflorin (PF), extracted from the peony root, has been proved to possess
      antineoplastic activity in different cancer cell lines. However, it remains
      unclear whether PF has an antineoplastic effect against osteosarcoma cells. The
      present study investigated the effects and the specific mechanism of PF on
      various human osteosarcoma cell lines. Using the multiple methods to detect the
      activity of PF on HOS and Saos-2 human osteosarcoma cell lines, including an MTS
      assay, flow cytometry, transmission electron microscopy and western blotting, it
      was demonstrated that PF induces inhibition of proliferation, G2/M phase cell
      cycle arrest and apoptosis in the osteosarcoma cell lines in vitro, and
      activation of cleaved-caspase-3 and cleaved-poly (ADPribose) polymerase in a dose
      dependent manner. Furthermore, the pro-apoptotic factors Bcl-2 X-associated
      protein and BH3 interacting domain death agonist were uregulated, while the anti
      apoptotic factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-extra large were
      downregulated. In conclusion, these results demonstrated that PF has a promising
      therapeutic potential in for osteosarcoma.

PMID- 29363723
TI  - Application of antibodies against Borna disease virus phosphoprotein and
      nucleoprotein on paraffin sections.
AB  - In order to study the application of antibodies against recombinant proteins for
      detecting Borna disease virus (BDV) phosphoprotein (p24) and nucleoprotein (p40)
      (BDV-p24/p40) on paraffin sections by immunohistochemistry. The purified fusion
      p24 and p40 proteins were used for the preparation of polyclonal and monoclonal
      anti-p24 and anti-40 antibodies, which were confirmed by ELISA and western
      blotting. Paraffin sections were made from BDV-infected Sprague-Dawley (SD) rats
      (n=20), PBS-injected SD rats (n=20), normal SD rats (n=20) and normal C57 mice
      (n=20). Immunohistochemical staining was performed according to the EnVisionTM
      two-step protocol. Heat-mediated antigen retrieval was performed using the
      retrieval buffer sodium citrate (1 mM; pH 6.0). All the antibodies against
      recombinant proteins exhibited good sensitivity and specificity. There were
      significant differences between the BDV-infected group and the BDV-uninfected
      group for poly- and monoclonal anti-p24 and -p40 antibodies. These antibodies
      against recombinant proteins may be used effectively to detect BDV p24 and p40 in
      paraffin sections.

PMID- 29363722
TI  - Therapeutic effects of beta-elemene via attenuation of the Wnt/beta-catenin
      signaling pathway in cervical cancer cells.
AB  - Concurrent radio chemotherapy treatment prolongs the survival rate of patients
      with advanced cervical cancer; however, it has adverse side-effects. beta
      elemene, an active component of the traditional Chinese medicinal herb Curcuma
      zedoaria, is a promising alternative therapeutic drug for the treatment of
      advanced cervical cancer. The aim of the present study was to investigate the
      antitumor effects of beta-elemene in human cervical cancer SiHa cells and to
      determine its underlying therapeutic molecular mechanisms. Cell viability, cell
      cycle progression and apoptosis were detected using an MTT assay and flow
      cytometry analysis. Furthermore, the levels of cell migration and cell invasion
      were investigated using Transwell and wound healing assays. The expression levels
      of Cyclin-dependent kinase inhibitor 2B (P15), Cyclin D1, cellular tumor antigen
      p53, apoptosis regulator Bcl-2 (Bcl-2), apoptosis regulator BAX (Bax), 72 kDa
      type IV collagenase (MMP-2), matrix metalloproteinase-9 (MMP-9), beta-catenin,
      transcription factor 7 (TCF7), and Myc proto-oncogene protein (c-Myc) were
      analyzed via western blotting. The results revealed that beta-elemene inhibited
      the proliferation of SiHa cells in a dose and time-dependent manner.
      Administration of beta-elemene induced G1 phase cell-cycle arrest, as
      demonstrated by the upregulation of P15 expression and the downregulation of
      Cyclin D1 expression. Furthermore, the present study revealed that beta-elemene
      induced apoptosis in SiHa cells by enhancing the expression of p53 and Bax, and
      suppressing the expression of Bcl-2. In addition, treatment with beta-elemene
      inhibited cell migration and invasion via downregulation of MMP-2 and MMP-9
      expression levels. Western blotting demonstrated that beta-elemene reduced the
      expression levels of beta-catenin and its downstream target molecule TCF7, thus
      resulting in reduced levels of their target proteins, including c-Myc, Cyclin D1,
      Bax and MMP-2 in cervical cancer cells. The results of the present study
      suggested that beta-elemene may inhibit cell proliferation and invasion, in
      addition to inducing apoptosis, via attenuation of the Wnt/beta-catenin signaling
      pathway in cervical cancer cells.

PMID- 29363724
TI  - Effect of bone marrow mesenchymal stem cells on the polarization of macrophages.
AB  - Inflammation is a defensive response in the living tissue of the vascular system
      that acts against damage factors and involves various types of immune cells,
      including macrophages, neutrophils, endothelial cells and other associated immune
      molecules. If the release of inflammatory mediators is excessive, systemic
      inflammatory response syndrome may develop. Sepsis is the most common
      complication of severe burns and is a systemic inflammatory response syndrome
      that is caused by infectious factors and is capable of leading to multiple organ
      dysfunction and potentially death. Research concerning the mechanism and
      treatment of sepsis is crucial. Macrophages are an important type of immune cell
      that remove invasive pathogens and are involved in innate and adaptive immune
      responses. It has been previously reported that bone marrow mesenchymal stem
      cells (BMSCs) affect macrophages by regulating immunity. The present study aimed
      to investigate the effect of BMSCs on macrophage polarization in vivo and in
      vitro, in addition to the potential therapeutic effect of these cells on
      experimental sepsis. BMSCs and peritoneal macrophages were isolated from Sprague
      Dawley rats and co-cultured overnight as a mixed culture or Transwell system, and
      subsequently stimulated with 100 ng/ml lipopolysaccharide (LPS). After 12 h, the
      medium was replaced with normal complete medium for various durations and
      supernatants were collected to extract proteins and cells for ELISA, western blot
      and flow cytometry analysis to investigate different aspects of macrophages.
      Sepsis was induced in Sprague-Dawley rats by injection of LPS (5 mg/kg), followed
      by tail vein injection of BMSCs or PBS 1 h later. After 6, 12, 24 and 48 h, lung
      tissues were harvested for pathological observation and peritoneal macrophages
      were collected for flow cytometry analysis to assess the expression of markers,
      including cluster of differentiation (CD)68 (used for gating), CD11c and CD206.
      The results demonstrated that, in the culture medium, LPS stimulation increased
      the expression of CD11c in macrophages, and the levels of tumor necrosis factor
      alpha and inducible nitric oxide synthase were also increased. By contrast, in
      macrophages treated with BMSCs directly, the expression of CD11c was reduced
      compared with the LPS-stimulated macrophage alone group. However, the secretion
      of interleukin-10, transforming growth factor-beta and arginase-1 was increased
      in the direct co-culture group, compared with the LPS-stimulated macrophage alone
      group. BMSCs reduced the inflammation in lung tissues and inhibited macrophage
      expression of CD11c in the rat model of sepsis. The results of the present study
      demonstrated that BMSCs co-cultured with macrophages directly inhibited
      macrophage differentiation into the M1 phenotype and reduced inflammation in
      macrophages stimulated by LPS. In vivo, BMSCs decreased the expression of CD11c
      in peritoneal macrophages and reduced the pathological inflammatory response in
      the lungs. The findings of the present study demonstrated that BMSCs may reduce
      the extent of the systemic inflammatory response, which may contribute to the
      development for a novel type of treatment for sepsis in the future.

PMID- 29363725
TI  - Low-dose dexamethasone affects osteoblast viability by inducing autophagy via
      intracellular ROS.
AB  - Glucocorticoids (GCs) are closely associated with the progression of GC-induced
      osteoporosis (GIOP) by inhibiting osteoblast viability. However, endogenous GCs
      are important for bone development. In addition, previous studies have
      demonstrated that GCs could induce autophagy, a cytoprotective process that is
      protective against various stressors. In the present study, the aim is to explore
      whether osteoblasts exhibited dose-dependent viability in the presence of GCs due
      to autophagy. hFOB 1.19 osteoblasts were treated with various doses of
      dexamethasone (DEX; 10-8-10-4 M) for 0, 24, 48 and 72 h. The results revealed a
      biphasic effect of DEX on the viability of hFOB 1.19 cells; a high dose of DEX
      (>=10-6 M) accelerated cell apoptosis, while a low dose of DEX (10-8 M) increased
      cell viability. Furthermore, significantly increased autophagy was observed in
      the low dose DEX treatment group, as indicated by the expression of the autophagy
      associated proteins beclin 1 and microtubule-associated protein light chain 3,
      and the detection of autophagosomes. Another finding was that DEX upregulated
      intracellular reactive oxygen species (ROS), which was decreased by the autophagy
      agonist rapamycin. The increase in autophagy and cell viability associated with
      low-dose DEX (10-8 M) was suppressed by the ROS scavenger catalase and the
      autophagy inhibitor 3-methyladenine. In conclusion, the results revealed that GCs
      affected osteoblast viability in a dose-dependent manner. A low dose of GCs
      increased osteoblast viability by inducing autophagy via intracellular ROS. The
      results indicate that autophagy may be a novel mechanism by which osteoblasts
      survive GC exposure and provide a potential therapeutic target for treating GIOP.

PMID- 29363726
TI  - Inhibitory effect of Patrinia on BRL-3A cell apoptosis through the
      TLR4/PI3K/AKT/GSK3beta and TLR4/P38/JNK signaling pathways.
AB  - The present study investigated the inhibitory effect of Patrinia on
      lipopolysaccharide (LPS)-induced apoptosis of rat liver BRL-3A cells. A Cell
      Counting Kit-8 assay was performed to measure the effect of Patrinia on BLR-3A
      cell activities. A biochemical assay was employed to detect the release of
      lactate dehydrogenase (LDH) in BRL-3A cells induced by different doses of LPS.
      Based on the release rate of LDH, drug concentrations were set at 0.5, 1 and 2
      g/l. Apoptotic morphology of cells was observed via Hoechst 33342 staining and
      flow cytometry was performed to detect apoptosis rates. Western blotting was
      performed to detect the expression of toll-like receptor 4 (TLR4), protein kinase
      B (AKT), phosphorylated (P)-AKTSer473, glycogen synthase kinase 3beta (GSK3beta),
      P-GSK3betaSer9, P38, P-P38, c-Jun N-terminal kinase (JNK), P-JNK, B-cell lymphoma
      2 (Bcl-2), Bcl-2 associated X protein (Bax) and active-caspase-3 proteins. The
      translocation of GSK3beta was observed by immunofluorescence staining. Results
      revealed that Patrinia increases cell activities and inhibits apoptosis. The
      expression levels of TLR4, P-P38 and P-JNK were reduced, whereas the expression
      of P-AKTSer473 and P-GSK3betaSer9 were increased. Patrinia significantly reduced
      GSK3beta nuclear translocation induced by LPS, and significantly decreased the
      mRNA expression levels of Bax/Bcl-2 and caspase-3 in BRL-3A cells induced by LPS.
      In conclusion, Patrinia may significantly reduce apoptosis of BRL-3A induced by
      LPS via the TLR4/PI3K/AKT/GSK3beta and TLR4/P38/JNK signaling pathways, providing
      evidence for its potential use in liver disease therapy.

PMID- 29363727
TI  - Protective effect of SIRT3 on acute lung injury by increasing manganese
      superoxide dismutase-mediated antioxidation.
AB  - Prolonged exposure to hyperoxia results in acute lung injury (ALI). Pulmonary
      damage caused by oxygen toxicity occurs due to the generation of reactive oxygen
      species and subsequent formation of more potent oxidants. The present study
      demonstrated that sirtuin 3 (SIRT3) may attenuate hyperoxia-induced ALI due to
      its potential antioxidative effect. In the present study, a hyperoxia-induced
      acute lung injury mouse model, reverse transcription-quantitative polymerase
      chain reaction, western blotting, retroviral mediated gene over-expression and
      knockdown assays revealed that the expression of SIRT3 in the lung tissue of mice
      with hyperoxia-induced ALI was decreased and overexpression of SIRT3 may
      significantly reduce hyperoxia-induced ALI, as reflected by decreases in protein
      concentration, infiltrated neutrophils in bronchoalveolar lavage (BAL) fluid and
      wet/dry ratio of lung tissues. Furthermore, overexpression of SIRT3 increased the
      protein levels and enzymatic activity of manganese superoxide dismutase (MnSOD),
      and inhibited oxidative stress in the lungs of ALI mice. Additionally, the
      current study demonstrated that SIRT3 promoted the expression of MnSOD, and this
      regulation was crucial for the protective effect of SIRT3 on hyperoxia-induced
      ALI. In summary, the results of the current study indicated that SIRT3
      overexpression may effectively ameliorate hyperoxia-induced ALI in mice, which
      indicates a potential application for SIRT3-based gene therapy to treat clinical
      adult respiratory distress syndrome.

PMID- 29363728
TI  - Interleukin-17 induces angiogenesis in vitro via CXCL8 and CCL2 in retinal
      pigment epithelium.
AB  - Interleukin-17 (IL-17) is a major pro-inflammatory cytokine involved in choroidal
      endothelial cell (CEC) angiogenesis. Proteins expressed by the retinal pigment
      epithelium (RPE) may contribute to CEC angiogenesis. The ability of IL-17 to
      promote proliferation, migration and capillary-like structure formation in CECs
      was investigated by stimulating the RPE in vitro. CECs were cultured in a
      conditioned medium (CM) with IL-17 (IL-17-CM) or without IL-17 (CM) obtained from
      the supernatant of an ARPE-19 cell line. The pro-angiogenic role of IL-17-CM on
      CECs was investigated with water-soluble tetrazolium 1 analysis, wound healing
      and Matrigel matrix tube formation assays. The expression level of vascular
      endothelial growth factor was detected by enzyme-linked immunosorbent assay in
      RPE cells treated with or without IL-17. Ras-related C3botulinum toxin substrate
      1 (Rac1) and Ras homolog gene family member A (RhoA) activities were analyzed by
      pull-down assays. IL-17-CM significantly enhanced tube formation and increased
      the migration distance in CECs in comparison with CM. This effect was diminished
      by neutralizing C-C motif chemokine 2 (CCL2) and C-X-C motif chemokine ligand 8
      (CXCL8) expression in IL-17-CM, with a concomitant downregulation of Rac1 and
      RhoA activity in CECs. In conclusion, it was demonstrated that IL-17 mediated the
      expression of CCL2 and CXCL8 in RPE cells, resulting in increased migration and
      tube formation in human CECs.

PMID- 29363729
TI  - (-)-Epigallocatechin-3-gallate modulates peripheral immunity in the MPTP-induced
      mouse model of Parkinson's disease.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is the most widely studied catechin in
      green tea and has been identified to regulate immune function. The objective of
      the present study was to explore the possible application of EGCG in the
      treatment of Parkinson's disease (PD) by examining its effects on the peripheral
      immune system in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      PD mouse model. The results demonstrated that EGCG treatment restored the
      movement behavior of the mice impaired by MPTP, and protected tyrosine
      hydroxylase-positive cells in the substantia nigra pars compacta region from MPTP
      toxicity. Flow cytometric analysis indicated that the ratio of CD3+CD4+ to
      CD3+CD8+ T lymphocytes in the peripheral blood increased in MPTP-treated mice
      following treatment with EGCG, and EGCG reduced expression of inflammatory
      factors tumor necrosis factor-alpha and interleukin-6 in serum. The present
      findings indicated that EGCG serves neuroprotective effects in an MPTP-induced PD
      mice model and may exert this through modulating peripheral immune response.

PMID- 29363731
TI  - Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through the Akt/GSK3beta
      signaling pathway in human cervical cancer cells.
AB  - Ginsenoside 20(S)-Rh2 (GRh2) is a bioactive compound derived from ginseng that is
      believed to maintain health in traditional Chinese medicine. Emerging evidence
      has suggested that GRh2 exhibits anti-cancer activity. The present study
      hypothesized that GRh2 has an anti-cancer function in human cervical cancer
      cells. An MTS assay demonstrated that GRh2 attenuated proliferation of HeLa cells
      in a dose- and time-dependent manner. In addition, GRh2 inhibited migration and
      invasion, as determined by wound healing and transwell invasion assays,
      respectively. Furthermore, GRh2 treatment reduced expression of mesenchymal
      markers N-cadherin and vimentin as well as epithelial mesenchymal transition
      transcriptional factor zinc finger E-box-binding homeobox 1 and snail1, and
      increased the protein expression levels of epithelial marker E-cadherin. In
      addition, the results revealed that GRh2 prevented activation of the protein
      kinase B (Akt)/glycogen synthase kinase (GSK)3beta signaling pathway in HeLa
      cells. In conclusion, the results suggested that GRh2 inhibits cervical cancer
      cell proliferation by targeting the Akt pathway, and prevents cervical cancer
      cell migration and invasion by suppressing the Akt/GSK3beta regulated EMT
      process, and therefore, GRh2 may have the potential to be a novel anti-cancer
      agent for cervical cancer.

PMID- 29363730
TI  - The roles of TRIO and F-actin-binding protein in glioblastoma cells.
AB  - TRIO and F-actin-binding protein (TrioBP), which was initially discovered as a
      binding partner of Trio and F-actin, is a critical factor associated with hearing
      loss in humans. However, the function of TrioBP in cancer has not been
      investigated. In the present study, TrioBP expression was indicated to be highly
      elevated in U87-MG and U343-MG cells. Furthermore, the TrioBP mRNA expression
      level was markedly increased in U87-MG and U251-MG cells compared with that in
      cerebral cortex cells, as determined by deep sequencing. Comprehensive analysis
      of a public TCGA dataset confirmed that TrioBP expression is elevated in patients
      with glioblastoma. In summary, the present data indicate that TrioBP expression
      is increased in glioblastoma cell lines and in patients with glioma, suggesting
      that TrioBP has potential as a diagnostic marker or therapeutic agent for glioma.

PMID- 29363732
TI  - Antagonist targeting microRNA-146a protects against lithium-pilocarpine-induced
      status epilepticus in rats by nuclear factor-kappaB pathway.
AB  - Previous studies have indicated that nuclear factor-kappaB (NF-kappaB) has an
      important role in the pathogenesis of epilepsy. The aim of the present study was
      to evaluate the expression of microRNA (miRNA)-146a, phosphorylated (p)-P65/P65,
      B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein (Bax) and pro-inflammatory
      cytokines, such as interleukin (IL)-6, IL-1beta and tumor necrosis factor (TNF
      alpha) in the brain tissue of rats with epilepsy. Sprague-Dawley rats were used
      to establish the epilepsy model using the lithium-pilocarpine method. The
      expression of miR-146a, pro-inflammatory cytokines, P-glycoprotein (P-gp), Bcl
      2/Bax and p-P65/P65 were assessed by reverse transcription-semi-quantitative
      polymerase chain reaction, enzyme-linked immunosorbent assay and western
      blotting, respectively. Hematoxylin and eosin staining was used to determine the
      pathology of epilepsy. The current findings revealed that the expression of miR
      146a was greater in the model group compared with the control group, and that the
      expression of miR-146a reached a maximum at 7 days post-treatment. The expression
      levels of IL-1beta, IL-6 and TNF-alpha were significantly reduced in the miR-146a
      antagonist group when compared with the model group. Additionally, the expression
      levels of P-gp and p-P65/P65 were significantly reduced following the addition of
      the miR-146a antagonist, whereas the expression levels of Bcl-2/Bax significantly
      increased under the same conditions. Therefore, the NF-kappaB pathway and miR
      146a may be potential therapeutic targets in the treatment of epilepsy.

PMID- 29363733
TI  - Generation of specific antisera directed against D-amino acids: focus on the
      neuroanatomical distribution of D-glutamate and other D-amino acids.
AB  - This review updates the findings about the anatomical distribution (using
      immunohistochemical techniques) and possible functions of D-glutamate in the
      central nervous system of mammals, as well as compares the distribution of D
      glutamate with the distribution of the most studied D-amino acids: D-serine and D
      aspartate. The protocol used to obtain highly specific antisera directed against
      D-amino acids is also reported. Immunoreactivity for D-glutamate was found in
      dendrites and cell bodies, but not in nerve fibers. Perikarya containing D
      glutamate were found in the mesencephalon and thalamus. The highest density of
      cell bodies was found in the dorsal raphe nucleus, the mesencephalic central grey
      matter, the superior colliculus, and in the subparafascicular thalamic nucleus.
      In comparison with the distribution of immunoreactive cell bodies containing D
      serine or D-aspartate, the distribution of D-glutamate-immunoreactive perikarya
      is less widespread. Currently, the physiological actions mediated by D-glutamate
      in the brain are unknown but the restricted neuroanatomical distribution of this
      D-amino acid suggests that D-glutamate could be involved in very specific
      physiological mechanisms. In this sense, the possible functional roles of D
      glutamate are discussed.

PMID- 29363734
TI  - Relationships between morphometrical properties and the texture of an extrusion
      expanded snack made from squid mantle (Dosidicus gigas).
AB  - : The giant squid (Dosidicus gigas) is a species of commercial interest as a
      source of protein, and it can be developed into ready-to-eat food products,
      including expanded extrusion snacks (EES). EES are prepared primarily from
      starch; however, adding animal protein increases the nutritional contents. The
      objective of this study was to evaluate the effect of the protein-carbohydrate
      interactions on the physical and morphological characteristics of an EES made of
      squid mantle and potato-corn flour. The independent variable was the squid mantle
      content (40, 60, 80, and 100%) and two controls (01  = 100% potato, 02  = 100%
      corn). The expansion rate (ER) of the sample is significantly minor (p < .5) when
      the squid mantle content increases ER = 2.0, 1.8 1.4 to 40, 60, and 80%,
      respectively. In samples with more protein, crispness and crunchiness were
      reduced, whereas the hardness increased. Digital imaging analysis indicated that
      the interaction between protein and starch causes significant morphometric
      changes to the fractal dimension (2.665-2.739) and lacunarity (0.61-1.29). The
      results showed that it is possible to incorporate up to 60% squid mantle to
      prepare EES that possess texture and morphometric characteristics competitive in
      reported studies with snacks usually incorporating flours, corn, and wheat in the
      formulations. PRACTICAL APPLICATIONS: The giant squid is a very attractive
      species because its meat has low caloric intake, high protein content, and is an
      important source of omega 3 fatty acids. Despite the desirable qualities of the
      squid meat its consumption is very low due to the low diffusion of the properties
      of its meat, acid, and ammoniacal flavor, rigid texture that requires prolonged
      cooking times and lack of alternatives of consumption. In Mexico, this type of
      squid is mainly destined for export as frozen mantle and products with little
      added value, which generates little economic benefit. Therefore, the results of
      this research may be of interest to the squid processing industry, which demands
      new forms of consumption of this marine species to increase their
      commercialization and added value.

PMID- 29363735
TI  - Graft-versus-host disease-associated hepatic portal venous gas.

PMID- 29363736
TI  - Potential influence of concomitant chemotherapy on CXCR4 expression in receptor
      directed endoradiotherapy.

PMID- 29363737
TI  - Relationship between Mental Health and Burden among Primary Caregivers of
      Outpatients with Schizophrenia.
AB  - There is growing recognition that caring for a patient with schizophrenia often
      results in high levels of perceived burden and poorer overall mental health for
      caregivers. A quantitative cross-sectional design and standardized instruments
      were used to collect data from 355 primary caregivers of adults in outpatient
      care with schizophrenia in China. Structural equation modeling was used to
      examine the association between caregiver burden and mental health among primary
      caregivers and whether this association is influenced by personality, coping
      style, and family functioning, based on a diathesis-stress perspective. Goodness
      of-fit indices (chi2 /df = 1.406, GFI = 0.919, CFI = 0.957, etc.) confirmed that
      the modified model fit the data well. In line with the diathesis-stress model,
      and with this study's hypotheses, we found that caregiver burden was
      significantly related to mental health outcomes directly. The final model showed
      that personality traits, coping style, and family function influenced the
      relationship between caregiver burden and mental health. The neuroticism
      personality traits have a direct effect on caregiver burden and family
      functioning in this sample. Coping style had a direct effect on the caregiver
      burden, and family functioning had a direct effect on the caregiver burden. Our
      final model about primary caregivers can be applied clinically to predict mental
      health outcomes from caregiver burden.

PMID- 29363739
TI  - Assessing complete remission status in incurable follicular lymphomas, to what
      purpose?

PMID- 29363738
TI  - Aeroallergen sensitization predicts acute chest syndrome in children with sickle
      cell anaemia.
AB  - Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso
      occlusive pain episodes among children with sickle cell anaemia (SCA).
      Aeroallergen sensitization is a risk factor for asthma. We hypothesized that
      aeroallergen sensitization is associated with an increased incidence of
      hospitalizations for ACS and pain. Participants in a multicentre, longitudinal
      cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten
      aeroallergens. ACS and pain episodes were collected from birth until the end of
      the follow-up period. The number of positive skin tests were tested for
      associations with prospective rates of ACS and pain. Multivariable models
      demonstrated additive effects of having positive skin tests on future rates of
      ACS (incidence rate ratio (IRR) for each positive test 1.23, 95% confidence
      interval [CI] 1.11-1.36, P < 0.001). Aeroallergen sensitization was not
      associated with future pain (IRR 1.14, 95%CI 0.97-1.33, P = 0.11). Our study
      demonstrated that children with SCA and aeroallergen sensitization are at
      increased risk for future ACS. Future research is needed to determine whether
      identification of specific sensitizations and allergen avoidance and treatment
      reduce the risk of ACS for children with SCA.

PMID- 29363740
TI  - The "escape" model: a versatile mechanism for clonal expansion.

PMID- 29363741
TI  - Adapting and Pilot Testing a Parenting Intervention for Homeless Families in
      Transitional Housing.
AB  - Intervention adaptation is a promising approach for extending the reach of
      evidence-based interventions to underserved families. One highly relevant
      population in need of services are homeless families. In particular, homeless
      families with children constitute more than one third of the total homeless
      population in the United States and face several unique challenges to parenting.
      The purpose of this study was to adapt and pilot test a parenting intervention
      for homeless families in transitional housing. An established adaptation model
      was used to guide this process. The systematic adaptation efforts included: (a)
      examining the theory of change in the original intervention, (b) identifying
      population differences relevant to homeless families in transitional housing, (c)
      adapting the content of the intervention, and (d) adapting the evaluation
      strategy. Next, a pilot test of the adapted intervention was conducted to examine
      implementation feasibility and acceptability. Feasibility data indicate an
      intervention spanning several weeks may be difficult to implement in the context
      of transitional housing. Yet, acceptability of the adapted intervention among
      participants was consistently high. The findings of this pilot work suggest
      several implications for informing continued parenting intervention research and
      practice with homeless families in transitional housing.

PMID- 29363742
TI  - Treatment with bortezomib in dense deposit disease associated with monoclonal
      gammopathy of undetermined significance.

PMID- 29363743
TI  - Diagnostic approach to pulmonary embolism in pregnancy: are the winds of change
      upon us or is it deja vu all over again?

PMID- 29363744
TI  - Serum hepcidin potentially identifies iron deficiency in survivors of critical
      illness at the time of hospital discharge.

PMID- 29363745
TI  - Marital Processes Linking Gender Role Attitudes and Marital Satisfaction Among
      Mexican-Origin Couples: Application of an Actor-Partner Interdependence Mediation
      Model.
AB  - Informed by dyadic approaches and culturally informed, ecological perspectives of
      marriage, we applied an actor-partner interdependence mediation model (APIMeM) in
      a sample of 120 Mexican-origin couples to examine (a) the associations linking
      Mexican immigrant husbands' and wives' gender role attitudes to marital
      satisfaction directly and indirectly through marital processes (i.e., warmth and
      negativity) and (b) whether the associations between spouses' gender role
      attitudes and marital processes were moderated by wives' employment. Although
      previous research has identified spouses' gender role attitudes as potential
      predictors of spouses' marital satisfaction, no study has examined these links in
      a dyadic model that elucidates how gender role attitudes may operate through
      processes to shape marital satisfaction and conditions under which associations
      may differ. We found that when spouses reported less sex-typed attitudes, their
      partners reported feeling more connected to them and more satisfied with the
      marriage, regardless of whether wives were employed. Our results suggest that
      marital satisfaction was highest for those Mexican-origin couples in which
      marital partners were less sex-typed in their attitudes about marital roles to
      the extent that partners' attitudinal role flexibility promoted spouses' feelings
      of warmth and connection to their partner.

PMID- 29363746
TI  - Empirically derived lifespan polytraumatization typologies: A systematic review.
AB  - CONTEXT: Polytraumatization classes based on trauma endorsement patterns relate
      to distinct clinical outcomes. Person-centered approaches robustly evaluate the
      nature, and construct validity of polytraumatization classes. OBJECTIVE: Our
      review examined evidence for the nature and construct validity of lifespan
      polytraumatization typologies. DATA SOURCES: In September 2016, we searched
      Pubmed, PSYCINFO, PSYC ARTICLES, Academic Search Complete, PILPTS, Web of
      Science, CINAHL, Medline, PsycEXTRA, and PBSC. Search terms included "latent
      profile," "latent class," "latent analysis," "person-centered," "polytrauma,"
      "polyvictimization," "traumatization," "lifetime," "cooccurring," "complex,"
      "typology," "multidimensional," "sequential," "multiple," "subtype,"
      "(re)victimization," "cumulative," "maltreatment," "abuse," and "stressor."
      Inclusionary criteria included: peer-reviewed; latent class/latent profile
      analyses (LCA/LPA) of lifespan polytrauma classes; adult samples of size greater
      than 200; only trauma types as LCA/LPA indicators; mental health correlates of
      typologies; and individual-level trauma assessment. Of 1,397 articles, nine met
      inclusion criteria. DATA EXTRACTION: Following Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) guidelines, research assistants
      completed a secondary reference search, and independently extracted data with
      standardized coding forms. RESULTS: Three-class (n = 5) or four-class (n = 4)
      solutions were found. Seven studies found a class characterized by higher trauma
      endorsement (high-trauma). All studies found a class characterized by lower
      trauma endorsement (low-trauma), and predominance of specific traumas (specific
      trauma; e.g., childhood maltreatment). High-trauma versus low-trauma classes and
      specific-trauma versus low-trauma classes differed on mental health correlates.
      CONCLUSION: Evidence supports the prevalence of a high-trauma class experiencing
      poorer mental health, and the detrimental impact of aggregated interpersonal and
      other traumas. We highlight the clinical importance of addressing
      polytraumatization classes, and comprehensively assessing the impact of all
      traumas.

PMID- 29363747
TI  - Attachment Versus Differentiation: The Contemporary Couple Therapy Debate.
AB  - This paper reviews the current debate between differentiation and attachment in
      treating couples through exploring the tenets of crucible therapy (Schnarch,
      1991) and emotionally focused couple therapy (Johnson, 2004). We provide a review
      of the two theories-as well as the two "pure form" example models-and explore the
      debate in light of the integrative movement in couple and family therapy (Lebow,
      2014). We also examine points of convergence of the two theories and models, and
      provide clinicians and researchers with an enhanced understanding of their
      divergent positions. Both differentiation and attachment are developmental
      theories that highlight the human experience of balancing individuality and
      connection in adulthood. The two models converge in terms of metaconcepts that
      pervade their respective theories and approach. Both models capitalize on the
      depth and importance of the therapeutic relationship, and provide rich case
      conceptualization and processes of therapy. However, they substantially differ in
      terms of how they view the fundamental aspects of adult development, have vastly
      divergent approaches to how a therapist intervenes in the room, and different
      ideas of how a healthy couple should function. In light of the deep polarization
      of the two models, points of integration-particularly between the broader
      theories of attachment and differentiation-are offered for therapists to
      consider.

PMID- 29363748
TI  - Haematology patients and the risk of transfusion transmitted infection.
AB  - A 2014 study by NHS Blood and Transplant indicated that over one quarter of red
      cells were transfused to patients with haematological conditions. For platelet
      components, the figure is higher. Certain diagnostic groups, such as
      haemoglobinopathies, myelodysplastic syndromes and some haemato-oncology
      patients, receive multiple transfusion episodes, either over long periods, or
      more intensively over shorter periods. Haematology patients account for the
      majority of the multi-transfused population. The risk of transfusion-transmitted
      infection (TTI) increases with number of donor exposures, and the consequences of
      TTI are often more significant in immunosuppressed individuals. Historically, use
      of pooled plasma products in patients with clotting disorders resulted in
      widespread transmission of hepatitis B virus, hepatitis C virus and human
      immunodeficiency virus before effective screening and viral inactivation methods
      were introduced.

PMID- 29363749
TI  - Effects of washing, soaking and domestic cooking on cadmium, arsenic and lead
      bioaccessibilities in rice.
AB  - BACKGROUND: The health risk of heavy metals such as cadmium (Cd), arsenic (As)
      and lead (Pb) in rice can be assessed by their concentration and
      bioaccessibility. In this work, japonica cultivar Xinfeng 2 and indica cultivar T
      You 15 were washed, soaked and cooked using three common domestic cooking
      methods. The present study investigated the effects of washing, soaking, normal
      cooking, high-pressure cooking and microwave cooking on the concentration,
      bioaccessibility and health risk of Cd, As and Pb in rice. RESULTS: Washing
      significantly reduced concentrations of Cd, As and Pb, and all three types of
      cooking reduced bioaccessibilities of these elements. No significant differences
      in bioaccessibility were observed among rice prepared with different cooking
      methods. Concentrations and bioaccessibilities of Cd, As and Pb highly affected
      the values of average daily dose, hazard quotient and lifetime cancer risk. High
      concentration and bioaccessibility cause As to pose non-carcinogenic and
      carcinogenic health risks to adults and children. Moreover, compared with adults,
      children have a high chance of exposure to non-carcinogenic and carcinogenic
      health risks. CONCLUSION: Washing and cooking of rice lowered the health risk by
      reducing Cd, As and Pb concentrations and bioaccessibilities respectively. (c)
      2018 Society of Chemical Industry.

PMID- 29363750
TI  - Potential effects of sulforaphane to fight obesity.
AB  - Obesity is linked to the onset of many diseases such as diabetes mellitus,
      cardiovascular diseases and cancer, among others. The prevalence of obesity
      nearly doubled worldwide between 1980 and 2014. Simultaneously, in the last
      decade, the effects of sulforaphane as a potential treatment for obesity have
      been investigated, with promising results. Fruits and vegetables and their
      processed agri-food co-products are good sources of natural health-promoting
      compounds. Brassica crops are among the most produced crops in the world and are
      a good source of glucoraphanin, which, following hydrolysis, releases
      sulforaphane. The Brassicaceae family generates large amounts of co-products with
      no intended use, causing negative economic and environmental impact. Valorization
      of these co-products could be achieved through their exploitation for the
      extraction of bioactive compounds such as sulforaphane. However, the extraction
      process still needs further improvement for its economic feasibility. This
      article reviews the potential effects of sulforaphane in the treatment of
      obesity, linked to the relevance of giving Brassica co-products added value,
      which is of key importance for the competitiveness of farmers and the agri-food
      industry. (c) 2018 Society of Chemical Industry.

PMID- 29363751
TI  - Inactivated antithombin as anticoagulant reversal in a rat model of
      cardiopulmonary bypass: a potent and potentially safer alternative to protamine.
AB  - Heparin anticoagulation followed by protamine reversal is commonly used in
      cardiopulmonary bypass (CPB). As an alternative to protamine, a recombinant
      inactive antithrombin (riAT) was designed as an antidote to heparin and was
      previously shown to be as potent as protamine in-vitro. In the present study,
      riAT was assessed for its ability to neutralize heparin after CPB in a rat model.
      After 60 min of CPB under heparin, rats received 5 mg/kg protamine, 37.5 mg/kg
      riAT or phosphate buffered saline (PBS) as placebo. Residual anticoagulant
      activity was assessed using the activated partial thromboplastin time assay
      before, and 10-30 min after reversion. Haemodynamic monitoring was performed and
      plasma histamine concentration was also measured. In this model, riAT appeared to
      be as efficient as protamine in neutralizing heparin. Ten minutes after
      injection, riAT and protamine both decreased heparin activity, to 1.8 +/- 1.3 and
      4.5 +/- 1.4 u/ml, respectively (23.1 +/- 5.1 u/ml in placebo group). Furthermore,
      evolution of mean carotid arterial pressure, heart rate and plasma histamine
      levels was comparable in rats treated with PBS or riAT, while protamine exhibited
      haemodynamic side effects and increased histamine plasma concentration. Thus,
      riAT could represent an advantage over protamine in CPB because it efficiently
      reverses heparin activity without negative effects on haemodynamic parameters and
      plasma histamine level.

PMID- 29363752
TI  - Ofatumumab is a feasible alternative anti-CD20 therapy in patients intolerant of
      rituximab.

PMID- 29363754
TI  - Mexican-Origin Parents' Stress and Satisfaction: The Role of Emotional Support.
AB  - Guided by a process model of parenting and the integrative model, this study
      examined sources of emotional support (i.e., partner, maternal, paternal) as
      related to stress and satisfaction resulting from the parenting role in a sample
      of Mexican-origin young adult parents who participated in the National
      Longitudinal Study of Adolescent to Adult Health (Add Health) during Wave IV.
      Participants were male and female parents (26-35 years of age; 59% female; N =
      737) who had children and a partner. Results from structural equation modeling
      revealed support from mothers as salient; high levels of maternal support were
      associated with high levels of parenting satisfaction. Tests of indirect effects
      suggested that parenting satisfaction played an intervening role in the link
      between maternal support and parenting stress. The pattern of results held across
      levels of linguistic acculturation but varied by gender. Understanding the
      mechanisms that predict parenting stress and satisfaction within the Mexican
      origin population may help in the identification of culturally sensitive
      intervention strategies.

PMID- 29363753
TI  - Activated leucocyte cell adhesion molecule (ALCAM/CD166) regulates T cell
      responses in a murine model of food allergy.
AB  - Food allergy is a major public health problem. Studies have shown that long-term
      interactions between activated leucocyte cell adhesion molecule (ALCAM/CD166) on
      the surface of antigen-presenting cells, and CD6, a co-stimulatory molecule,
      influence immune responses. However, there are currently no studies on the
      functions of ALCAM in food allergy. Therefore, we aimed to identify the functions
      of ALCAM in ovalbumin (OVA)-induced food allergy using ALCAM-deficient mice. Wild
      type (WT) and ALCAM-deficient (ALCAM-/- ) mice were sensitized intraperitoneally
      and with orally fed OVA. The mice were killed, and parameters related to food
      allergy and T helper type 2 (Th2) immune responses were analysed. ALCAM serum
      levels increased and mRNA expression decreased in OVA-challenged WT mice. Serum
      immunoglobulin (Ig)E levels, Th2 cytokine mRNA and histological injuries were
      higher in OVA-challenged WT mice than in control mice, and these were attenuated
      in ALCAM-/- mice. T cell proliferation of total cells, CD3+ CD4+ T cells and
      activated T cells in immune tissues were diminished in OVA-challenged ALCAM-/-
      mice. Proliferation of co-cultured T cells and dendritic cells (DCs) was
      decreased by the anti-CD6 antibody. In addition, WT mice sensitized by adoptive
      transfer of OVA-pulsed ALCAM-/- BM-derived DCs showed reduced immune responses.
      Lastly, serum ALCAM levels were higher in children with food allergy than in
      control subjects. In this study, serum levels of ALCAM were elevated in food
      allergy-induced WT mice and children with food allergy. Moreover, immune
      responses and T cell activation were attenuated in OVA-challenged ALCAM-/- mice.
      These results indicate that ALCAM regulates food allergy by affecting T cell
      activation.

PMID- 29363755
TI  - NQO1*2 polymorphism predicts overall survival in MDS patients.

PMID- 29363756
TI  - Structured emulsions as butter substitutes: effects on physicochemical and
      sensory attributes of shortbread cookies.
AB  - BACKGROUND: Reformulation of foods products to reduce total and saturated fats
      while maintaining acceptable structure, texture and mouthfeel poses an important
      challenge to the food industry. In this work, the use of structured emulsions
      (fibre-induced oil-in-water biphasic systems with reduced total and saturated
      fats) is proposed to replace butter in shortbread cookies. RESULTS: Use of
      structured emulsions resulted in softer dough that was still workable using a
      traditional process. Shortbread cookies containing structured emulsions were
      harder and paler than the butter control but had a significantly reduced
      saturated fat content. They also received promising scores in the sensory
      analysis in terms of texture and overall acceptability, despite the butter
      product still being the preferred sample. CONCLUSION: The results of this study
      indicated that structured emulsions represent a good solution to produce
      nutritionally improved shortbreads. Optimization of the structured emulsion
      formulation can provide further improvement of the nutritional, sensory and
      physicochemical properties of shortbread cookies. (c) 2018 Society of Chemical
      Industry.

PMID- 29363757
TI  - How I manage patients with cold agglutinin disease.
AB  - Cold agglutinin disease (CAD) is an uncommon autoimmune haemolytic anaemia in
      which a well-defined, clonal low-grade lymphoproliferative disorder of the bone
      marrow results in erythrocyte destruction mediated by the classical complement
      pathway. The pathogenesis, clinical features and diagnostic criteria are
      reviewed. Although anaemia is mild in some patients, approximately one-third of
      untreated patients have a haemoglobin level of <=80 g/l, and about 50% have been
      considered transfusion dependent for shorter or longer periods. Therapy has
      improved greatly during the last 15 years. Mild disease can be managed by
      avoidance of cold and adequate precautions in specific situations, without drug
      therapy. Corticosteroids should not be used to treat CAD. Patients requiring
      pharmacological therapy should be considered for prospective trials. Outside
      clinical studies, the rituximab-bendamustine combination or rituximab monotherapy
      is recommended in the first line, depending on individual patient
      characteristics. Second-line options are rituximab-fludarabine in fit patients
      or, although less strongly documented, a bortezomib-based regimen. Therapies
      targeting the classical complement pathway are promising, and the complement C1s
      inhibitor, BIVV009, has shown favourable results in preliminary studies.

PMID- 29363758
TI  - The impact of liver steatosis on the ability of serum ferritin levels to be
      predictive of liver iron concentration in non-transfusion-dependent thalassaemia
      patients.
AB  - This study analysed the impact of liver steatosis (LS) on the parameters of iron
      overload in 110 patients with non-transfusion dependent thalassaemia (NTDT). LS
      was diagnosed by ultrasound. Liver iron concentration (LIC) measurements were
      available for 64 patients who underwent a magnetic resonance imaging (MRI) scan.
      LS was frequent (35.5%) and was significantly more prevalent in males than in
      females (49.0% vs. 24.6%, P = 0.008). Patients with LS had significant higher
      levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      ALT/AST ratio and ferritin than those without, but LIC values were comparable. An
      ALT/AST ratio >0.89 predicted the presence of LS with a sensitivity of 0.872 and
      a specificity of 0.901 (P < 0.0001). Ferritin levels correlated with LIC values
      (R = 0.558, P < 0.0001) but the correlation was stronger in patients without LS
      (R = 0.656, P < 0.0001) than in patients with LS (R = 0.426, P = 0.05). LS is a
      frequent issue in NTDT patients and should be suspected in the presence of an
      ALT/AST ratio >0.89. Recently, serum ferritin thresholds that predict clinically
      relevant LIC for guiding iron chelation therapy when MRI is unavailable have been
      determined. Our data show that LS may cause increase in ferritin levels and may
      be responsible for anticipating/exceeding chelation treatment in NTDT patients in
      the absence of LIC evaluation.

PMID- 29363759
TI  - Estimates of global and regional prevalence of neural tube defects for 2015: a
      systematic analysis.
AB  - Neural tube defects (NTDs) are associated with substantial mortality, morbidity,
      disability, and psychological and economic costs. Many are preventable with folic
      acid, and access to appropriate services for those affected can improve survival
      and quality of life. We used a compartmental model to estimate global and
      regional birth prevalence of NTDs (live births, stillbirths, and elective
      terminations of pregnancy) and subsequent under-5 mortality. Data were identified
      through web-based reviews of birth defect registry databases and systematic
      literature reviews. Meta-analyses were undertaken where appropriate. For 2015,
      our model estimated 260,100 (uncertainty interval (UI): 213,800-322,000) NTD
      affected birth outcomes worldwide (prevalence 18.6 (15.3-23.0)/10,000 live
      births). Approximately 50% of cases were elective terminations of pregnancy for
      fetal anomalies (UI: 59,300 (47,900-74,500)) or stillbirths (57,800 (UI: 35,000
      88,600)). Of NTD-affected live births, 117,900 (~75%) (UI: 105,500-186,600)
      resulted in under-5 deaths. Our systematic review showed a paucity of high
      quality data in the regions of the world with the highest burden. Despite
      knowledge about prevention, NTDs remain highly prevalent worldwide. Lack of
      surveillance and incomplete ascertainment of affected pregnancies make NTDs
      invisible to policy makers. Improved surveillance of all adverse outcomes is
      needed to improve the robustness of total NTD prevalence estimation, evaluate
      effectiveness of prevention through folic acid fortification, and improve
      outcomes through care and rehabilitation.

PMID- 29363760
TI  - A comparison of gantry-mounted x-ray-based real-time target tracking methods.
AB  - PURPOSE: Most modern radiotherapy machines are built with a 2D kV imaging system.
      Combining this imaging system with a 2D-3D inference method would allow for a
      ready-made option for real-time 3D tumor tracking. This work investigates and
      compares the accuracy of four existing 2D-3D inference methods using both motion
      traces inferred from external surrogates and measured internally from implanted
      beacons. METHOD: Tumor motion data from 160 fractions (46 thoracic/abdominal
      patients) of Synchrony traces (inferred traces), and 28 fractions (7 lung
      patients) of Calypso traces (internal traces) from the LIGHT SABR trial
      (NCT02514512) were used in this study. The motion traces were used as the ground
      truth. The ground truth trajectories were used in silico to generate 2D positions
      projected on the kV detector. These 2D traces were then passed to the 2D-3D
      inference methods: interdimensional correlation, Gaussian probability density
      function (PDF), arbitrary-shape PDF, and the Kalman filter. The inferred 3D
      positions were compared with the ground truth to determine tracking errors. The
      relationships between tracking error and motion magnitude, interdimensional
      correlation, and breathing periodicity index (BPI) were also investigated.
      RESULTS: Larger tracking errors were observed from the Calypso traces, with RMS
      and 95th percentile 3D errors of 0.84-1.25 mm and 1.72-2.64 mm, compared to 0.45
      0.68 mm and 0.74-1.13 mm from the Synchrony traces. The Gaussian PDF method was
      found to be the most accurate, followed by the Kalman filter, the
      interdimensional correlation method, and the arbitrary-shape PDF method. Tracking
      error was found to strongly and positively correlate with motion magnitude for
      both the Synchrony and Calypso traces and for all four methods. Interdimensional
      correlation and BPI were found to negatively correlate with tracking error only
      for the Synchrony traces. The Synchrony traces exhibited higher interdimensional
      correlation than the Calypso traces especially in the anterior-posterior
      direction. CONCLUSION: Inferred traces often exhibit higher interdimensional
      correlation, which are not true representation of thoracic/abdominal motion and
      may underestimate kV-based tracking errors. The use of internal traces acquired
      from systems such as Calypso is advised for future kV-based tracking studies. The
      Gaussian PDF method is the most accurate 2D-3D inference method for tracking
      thoracic/abdominal targets. Motion magnitude has significant impact on 2D-3D
      inference error, and should be considered when estimating kV-based tracking
      error.

PMID- 29363761
TI  - From lesser-known to super vegetables: the growing profile of African traditional
      leafy vegetables in promoting food security and wellness.
AB  - There are hundreds of traditional leafy vegetables and wild food plants of
      horticultural and nutritional significance in Africa. These lesser-known crops
      and wild food plants that are highly adapted to harsh growing conditions thrive
      with little care and are available when other sources of food fail or are out of
      season. They are rich in micronutrients and are often the cheapest sources of
      many essential vitamins and minerals in many localities. Many of them are very
      important functional foods in African traditional diets and are rich in
      nutraceuticals, including polyphenols, tannins, flavonoids and flavonols, that
      exert demonstrable antioxidant, free radical scavenging and enzyme inhibition
      activities and have antimicrobial properties that provide scientific
      justification and possible mechanisms for their use in the management of a wide
      range of ailments, including diet-related, non-communicable diseases such as
      diabetes, hypertension and cardiovascular diseases. African traditional leafy
      vegetables are invaluable in promoting food security and wellness in Africa on
      account of their availability and affordability, their great nutritional value,
      chemotherapeutic and health-promoting properties and other unique qualities. Long
      recognised by the rural populace as quality food items, they are becoming more
      popular even with the more affluent urban elites. There is the need to develop
      improved management practices for these super vegetables to promote their
      cultivation and boost their exploitation for food security and wellness in
      Africa. (c) 2018 Society of Chemical Industry.

PMID- 29363762
TI  - A comparison of prostate tumor targeting strategies using magnetic resonance
      imaging-targeted, transrectal ultrasound-guided fusion biopsy.
AB  - PURPOSE: Magnetic resonance imaging (MRI)-targeted, three-dimensional (3D)
      transrectal ultrasound (TRUS)-guided prostate biopsy aims to reduce the 21-47%
      false-negative rate of clinical two-dimensional (2D) TRUS-guided systematic
      biopsy, but continues to yield false-negative results. This may be improved via
      needle target optimization, accounting for guidance system errors and image
      registration errors. As an initial step toward the goal of optimized prostate
      biopsy targeting, we investigated how needle delivery error impacts tumor
      sampling probability for two targeting strategies. METHODS: We obtained MRI and
      3D TRUS images from 49 patients. A radiologist and radiology resident assessed
      these MR images and contoured 81 suspicious regions, yielding tumor surfaces that
      were registered to 3D TRUS. The biopsy system's root-mean-squared needle delivery
      error (RMSE) and systematic error were modeled using an isotropic 3D Gaussian
      distribution. We investigated two different prostate tumor-targeting strategies
      using (a) the tumor's centroid and (b) a ring in the lateral-elevational plane.
      For each simulation, targets were spaced at equal arc lengths on a ring with
      radius equal to the systematic error magnitude. A total of 1000 biopsy
      simulations were conducted for each tumor, with RMSE and systematic error
      magnitudes ranging from 1 to 6 mm. The difference in median tumor sampling
      probability and probability of obtaining a 50% core involvement was determined
      for ring vs centroid targeting. RESULTS: Our simulation results indicate that
      ring targeting outperformed centroid targeting in situations where systematic
      error exceeds RMSE. In these instances, we observed statistically significant
      differences showing 1-32% improvement in sampling probability due to ring
      targeting. Likewise, we observed statistically significant differences showing 1
      39% improvement in 50% core involvement probability due to ring targeting.
      CONCLUSIONS: Our results suggest that the optimal targeting scheme for prostate
      biopsy depends on the relative levels of systematic and random errors in the
      system. Where systematic error dominates, a ring-targeting scheme may yield
      improved probability of tumor sampling. The findings presented in this paper may
      be used to aid in target selection strategies for clinicians performing targeted
      prostate biopsies on any MRI targeted, 3D TRUS-guided biopsy system and could
      support earlier diagnosis of prostate cancer while it remains localized to the
      gland and curable.

PMID- 29363764
TI  - Myasthenic syndromes due to defects in COL13A1 and in the N-linked glycosylation
      pathway.
AB  - The congenital myasthenic syndromes (CMS) are hereditary disorders of
      neuromuscular transmission. The number of cases recognized, at around 1:100,000
      in the United Kingdom, is increasing with improved diagnosis. The advent of next
      generation sequencing has facilitated the discovery of many genes that harbor CMS
      associated mutations. An emerging group of CMS, characterized by a limb-girdle
      pattern of muscle weakness, is caused by mutations in genes that encode proteins
      involved in the initial steps of the N-linked glycosylation pathway, which is
      surprising, since this pathway is found in all mammalian cells. However,
      mutations in these genes may also give rise to multisystem disorders (congenital
      disorders of glycosylation) or muscle disorders where the myasthenic symptoms
      constitute only one component within a wider phenotypic spectrum. We also report
      a CMS due to mutations in COL13A1, which encodes an extracellular matrix protein
      that is concentrated at the neuromuscular junction and highlights a role for
      these extracellular matrix proteins in maintaining synaptic stability that is
      independent of the AGRN/MuSK clustering pathway. Knowledge about the
      neuromuscular synapse and the different proteins involved in maintaining its
      structure as well as function enables us to tailor treatments to the underlying
      pathogenic mechanisms.

PMID- 29363763
TI  - Oral bisphosphonate use and age-related macular degeneration: retrospective
      cohort and nested case-control study.
AB  - Our objective here was to determine whether oral bisphosphonate (BP) use is
      associated with the incidence of age-related macular degeneration (AMD). We
      performed a population-based study using electronic health records from UK
      primary care (Clinical Practice Research Datalink). A cohort of 13,974 hip
      fracture patients (1999-2013) was used to conduct (1) a propensity score-matched
      cohort analysis and (2) a nested case-control analysis. Hip fracture patients
      were aged >=50 years without AMD diagnosis before hip fracture date or in the
      first year of follow-up. Among 6208 matched patients and during 22,142 person
      years of follow-up, 57 (1.8%) and 42 (1.4%) AMD cases occurred in BP users and
      non-BP users, respectively. The survival analysis model did not provide
      significant evidence of a higher risk of AMD in BP users (subhazard ratio: 1.60;
      95% confidence interval (CI): 0.95-2.72; P = 0.08), although there was a
      significant increased risk among BP users with high medication possession ratio
      (MPR) (top quartile) relative to non-BP users (odds ratio: 5.08, 95% CI: 3.11
      8.30; P < 0.001, respectively). Overall, oral BP use was not associated with an
      increased risk of AMD in this cohort of hip fracture patients, although the risk
      increased significantly with higher MPR. More data are needed to confirm these
      findings.

PMID- 29363765
TI  - The investment case for folic acid fortification in developing countries.
AB  - There is compelling evidence that neural tube defects can be prevented through
      mandatory folic acid fortification. Why, then, is an investment case needed? At
      the core of the answer to this question is the notion that governments and
      individuals have limited resources for which there are many competing claims. An
      investment case compares the costs and benefits of folic acid fortification
      relative to alternative life-saving investments and informs estimates of the
      financing required for implementation. Our best estimate is that the cost per
      death averted through mandatory folic acid fortification is $957 and the cost per
      disability-adjusted life year is $14.90. Both compare favorably to recommended
      life-saving interventions, such as the rotavirus vaccine and insecticide-treated
      bed nets. Thus, there is a strong economic argument for mandatory folic acid
      fortification. Further improvements to these estimates will require better data
      on the costs of implementing fortification and on the costs of improving
      compliance where regulations are already in place.

PMID- 29363768
TI  - Bitter taste masking of enzyme-treated soy protein in water and bread.
AB  - BACKGROUND: Bioactive protein hydrolysates are often very bitter. To overcome
      this challenge, xylitol, sucrose, alpha-cyclodextrin, maltodextrin and
      combinations of these were tested systematically as bitter-masking agents of an
      enzyme-treated soy protein in an aqueous model and in a bread model. Sensory
      descriptive analysis was used to reveal the bitter-masking effect of the taste
      masking blends on the enzyme-treated soy protein. RESULTS: In water, xylitol,
      sucrose and maltodextrin reduced bitterness significantly, whereas alpha
      cyclodextrin did not. No significant difference was observed in bitterness
      reduction between xylitol and sucrose. Both reduced bitterness significantly more
      than maltodextrin. No interactions between the taste-masking agents affecting
      bitterness reduction were found. Clearer bitter-masking effects were seen in the
      aqueous model compared with the bread model. The bitter-masking effects of alpha
      cyclodextrin and maltodextrin were similar between water and bread. The effect of
      xylitol and sucrose on bitterness suppression varied between the systems. In
      water, bitterness was negatively correlated with sweetness. In bread, bitterness
      was negatively correlated with freshness, and maltodextrin significantly reduced
      bitterness of the enzyme-treated soy protein and increased freshness. CONCLUSION:
      Bitter-masking effects were generally more discernible in the aqueous model
      compared with the bread model. (c) 2018 Society of Chemical Industry.

PMID- 29363767
TI  - Friendly fire: Longitudinal effects of exposure to violent video games on
      aggressive behavior in adolescent friendship dyads.
AB  - Research on gaming effects has focused on adolescence, a developmental period in
      which peer relationships become increasingly salient. However, the impact of
      peers on the effects of violent gaming on adolescents has been understudied. This
      study examined whether adolescents' exposure to violent video games predicted
      their own and their friend's aggression one year later. Among 705 gaming
      adolescents, 141 dyads were identified based on reciprocated best friend
      nominations (73.8% male, Mage  = 13.98). Actor-Partner Interdependence Models
      indicated that adolescent males' (but not females') exposure to violent games
      positively predicted the aggression of their best friend 1 year later. This
      effect appeared regardless of whether the friends played video games together or
      not. The study illustrates the importance of peers in the association between
      violent gaming and aggression.

PMID- 29363766
TI  - The role of autophagy in the regulation of yeast life span.
AB  - The goal of the aging field is to develop novel therapeutic interventions that
      extend human health span and reduce the burden of age-related disease. While
      organismal aging is a complex, multifactorial process, a popular theory is that
      cellular aging is a significant contributor to the progressive decline inherent
      to all multicellular organisms. To explore the molecular determinants that drive
      cellular aging, as well as how to retard them, researchers have utilized the
      highly genetically tractable budding yeast Saccharomyces cerevisiae. Indeed,
      every intervention known to extend both cellular and organismal health span was
      identified in yeast, underlining the power of this approach. Importantly, a
      growing body of work has implicated the process of autophagy as playing a
      critical role in the delay of aging. This review summarizes recent reports that
      have identified a role for autophagy, or autophagy factors in the extension of
      yeast life span. These studies demonstrate (1) that yeast remains an invaluable
      tool for the identification and characterization of conserved mechanisms that
      promote cellular longevity and are likely to be relevant to humans, and (2) that
      the process of autophagy has been implicated in nearly all known longevity
      promoting manipulations and thus represents an ideal target for interventions
      aimed at improving human health span.

PMID- 29363769
TI  - Characterization methods for comprehensive evaluations of shielding materials
      used in an MRI.
AB  - PURPOSE: In order to integrate electronic devices into a magnetic resonance
      imaging (MRI) scanner, shielding of the electronics with respect to the radio
      frequency (RF) transmit and receive system of the MRI scanner is required.
      Furthermore, MRI uses time-varying low-frequency magnetic fields for spatial
      encoding, i.e., the gradient magnetic fields. Time-varying magnetic fields induce
      eddy currents in all conductive elements. The eddy currents result in opposing
      magnetic fields, which can cause distortions of the magnetic resonance (MR)
      image. As shielding of lower frequencies is not feasible in this respect, an
      ideal shielding element should be transparent for gradient magnetic fields while
      providing a high RF shielding effectiveness. Furthermore, it should offer a low
      susceptibility to prevent distortion of the main magnetic field of the MRI. In
      this work, we characterize the aforesaid shielding parameters of different
      shielding samples. METHODS: We developed a nuclear magnetic resonance (NMR) probe
      to measure the magnetic fields to quantify the field distortions time-resolvedly.
      The relative distortion was introduced as a proportionality constant relating the
      eddy-current-inducing field changes and the field distortions. The relative
      distortion was measured in the frequency range from 0 to 10 kHz for all shielding
      samples using the NMR probe. We characterized the shielding effectiveness of the
      samples in the frequency range from 1 to 150 MHz using a network analyzer. We
      conducted all measurements with three different materials, two carbon fiber
      composites and copper, each in various thicknesses. RESULTS: The relative
      distortion of the magnetic fields induced by the carbon fiber composites samples
      was at least a factor of seven lower than the copper sample. A linear dependency
      on the sample thickness was measured for the main field distortion, the relative
      distortion and the shielding effectiveness. The relative distortion was roughly
      independent of the gradient frequency contrary to the shielding effectiveness,
      highly depending on the RF frequency. CONCLUSIONS: We presented a very sensitive
      method to characterize the distortion of the main field distortion and the
      gradient transparency using an NMR probe. We analyzed different shielding
      materials regarding the main field distortion, the gradient transparency, and the
      shielding effectiveness. From the tested materials, we identified a carbon fiber
      composite with the lowest distortion on the MRI.

PMID- 29363770
TI  - Assessment of image quality and scatter and leakage radiation of an integrated MR
      LINAC system.
AB  - PURPOSE: To assess the image quality, scatter, and leakage radiation of an
      integrated magnetic resonance linear accelerator (MR-LINAC or MRL) system.
      METHODS: A large American College of Radiology (ACR) magnetic resonance imaging
      (MRI) accreditation phantom was used to evaluate the MRI capabilities of the
      integrated MRL system compared with those of other diagnostic MRI systems.
      Multiple sets of T1 and T2/PD images were acquired with the linear accelerator
      positioned at various angles and with the radiation beam on and off. Images also
      were acquired on three different occasions over a period of about 12 months.
      Scatter and leakage radiation were measured with a large (150 cm3 ) ion chamber
      recalibrated for MV energy. For scatter measurements, a 25-cm stack of solid
      water materials was placed at the isocenter on the patient couch to simulate a
      patient. The head leakage was measured at 1 m from the linear accelerator head in
      directions determined to produce the maximum leakage. All measurements were
      repeated with the magnetic field turned off to study the effects of the magnetic
      field. RESULTS: The geometric distortion, slice thickness accuracy, image
      uniformity, ghosting ratio, and high-contrast detectability were comparable to
      other 1.5 T diagnostic MRI scanners. No observable changes in image quality and
      no appreciable differences were found between radiation beam-on and beam-off
      images. The measured leakage and scattered radiation changed by less than 5% when
      the magnetic field was on compared to measurements with the field off. The beam
      stopper leakage was approximately 0.3 R/1000 MU, and because there was no direct
      beam imparted on the walls, a vault designed for a modern-day LINAC should have
      enough required radiation shielding to house the MRL. CONCLUSIONS: The image
      quality generated by the MRI system of the integrated MRL was similar to that of
      a diagnostic MRI scanner. Interference from the MV radiation was minimal, and
      there was no measurable difference in image quality with the beam on and off.
      Scatter radiation and leakage radiation of the MRL system were within the
      expected range of a comparable MV-LINAC.

PMID- 29363771
TI  - Determining degree of roasting in cocoa beans by artificial neural network (ANN)
      based electronic nose system and gas chromatography/mass spectrometry (GC/MS).
AB  - BACKGROUND: Roasting is a critical step in chocolate processing, where moisture
      content is decreased and unique flavors and texture are developed. The
      determination of the degree of roasting in cocoa beans is important to ensure the
      quality of chocolate. Determining the degree of roasting relies on human
      specialists or sophisticated chemical analyses that are inaccessible to small
      manufacturers and farmers. In this study, an electronic nose system was
      constructed consisting of an array of gas sensors and used to detect volatiles
      emanating from cocoa beans roasted for 0, 20, 30 and 40 min. The several signals
      were used to train a three-layer artificial neural network (ANN). Headspace
      samples were also analyzed by gas chromatography/mass spectrometry (GC/MS), with
      23 select volatiles used to train a separate ANN. RESULTS: Both ANNs were used to
      predict the degree of roasting of cocoa beans. The electronic nose had a
      prediction accuracy of 94.4% using signals from sensors TGS 813, 826, 822, 830,
      830, 2620, 2602 and 2610. In comparison, the GC/MS predicted the degree of
      roasting with an accuracy of 95.8%. CONCLUSION: The electronic nose system is
      able to predict the extent of roasting, as well as a more sophisticated approach
      using GC/MS. (c) 2018 Society of Chemical Industry.

PMID- 29363772
TI  - Lessons from animal nutritionists: dietary amino acid requirement studies and
      considerations for healthy aging studies.
AB  - Dietary restriction (DR) increases median life span and protects against age
      related disease. Improved longevity can be achieved by restriction of dietary
      energy, protein, or amino acids (AAs), such as methionine (Met). Met requirements
      have been defined using methodologies that measure the dose response to Met when
      all other dietary variables are held constant and with outcomes focused on
      protein turnover. Here, we cover protein and sulfur AA requirements and discuss
      the terms "deficient," "optimal," and "excess" and how these need to be
      considered. We additionally discuss the effect of methyl-donating compounds on
      sulfur AA metabolism and outcomes. We will discuss how the mechanistic target of
      rapamycin complex 1 (mTORC1) signaling network regulates protein turnover,
      lipogenesis and cell growth, proliferation, differentiation, and metabolism in
      response to hormones, AAs, and cellular energy status. Inhibition of mTORC1
      signaling with rapamycin or genetic mutation increases median life span in model
      organisms, and mTORC1 inhibition may be responsible for some of the life span
      extending effects of DR. Finally, we discuss how the sulfur AAs may regulate
      aspects of reactive oxygen species (ROS) mitigation. Overall, we suggest that
      approaches evaluating AA intake need to consider whole-body protein synthesis and
      measures related to tissue-specific and whole-body metabolism that have been
      associated with longevity.

PMID- 29363774
TI  - Automated mammographic breast density estimation using a fully convolutional
      network.
AB  - PURPOSE: The purpose of this study was to develop a fully automated algorithm for
      mammographic breast density estimation using deep learning. METHOD: Our algorithm
      used a fully convolutional network, which is a deep learning framework for image
      segmentation, to segment both the breast and the dense fibroglandular areas on
      mammographic images. Using the segmented breast and dense areas, our algorithm
      computed the breast percent density (PD), which is the faction of dense area in a
      breast. Our dataset included full-field digital screening mammograms of 604
      women, which included 1208 mediolateral oblique (MLO) and 1208 craniocaudal (CC)
      views. We allocated 455, 58, and 91 of 604 women and their exams into training,
      testing, and validation datasets, respectively. We established ground truth for
      the breast and the dense fibroglandular areas via manual segmentation and
      segmentation using a simple thresholding based on BI-RADS density assessments by
      radiologists, respectively. Using the mammograms and ground truth, we fine-tuned
      a pretrained deep learning network to train the network to segment both the
      breast and the fibroglandular areas. Using the validation dataset, we evaluated
      the performance of the proposed algorithm against radiologists' BI-RADS density
      assessments. Specifically, we conducted a correlation analysis between a BI-RADS
      density assessment of a given breast and its corresponding PD estimate by the
      proposed algorithm. In addition, we evaluated our algorithm in terms of its
      ability to classify the BI-RADS density using PD estimates, and its ability to
      provide consistent PD estimates for the left and the right breast and the MLO and
      CC views of the same women. To show the effectiveness of our algorithm, we
      compared the performance of our algorithm against a state of the art algorithm,
      laboratory for individualized breast radiodensity assessment (LIBRA). RESULT: The
      PD estimated by our algorithm correlated well with BI-RADS density ratings by
      radiologists. Pearson's rho values of our algorithm for CC view, MLO view, and CC
      MLO-averaged were 0.81, 0.79, and 0.85, respectively, while those of LIBRA were
      0.58, 0.71, and 0.69, respectively. For CC view and CC-MLO averaged cases, the
      difference in rho values between the proposed algorithm and LIBRA showed
      statistical significance (P < 0.006). In addition, our algorithm provided
      reliable PD estimates for the left and the right breast (Pearson's rho > 0.87)
      and for the MLO and CC views (Pearson's rho = 0.76). However, LIBRA showed a
      lower Pearson's rho value (0.66) for both the left and right breasts for the CC
      view. In addition, our algorithm showed an excellent ability to separate each sub
      BI-RADS breast density class (statistically significant, p-values = 0.0001 or
      less); only one comparison pair, density 1 and density 2 in the CC view, was not
      statistically significant (P = 0.54). However, LIBRA failed to separate breasts
      in density 1 and 2 for both the CC and MLO views (P > 0.64). CONCLUSION: We have
      developed a new deep learning based algorithm for breast density segmentation and
      estimation. We showed that the proposed algorithm correlated well with BI-RADS
      density assessments by radiologists and outperformed an existing state of the art
      algorithm.

PMID- 29363773
TI  - Semi-automated pulmonary nodule interval segmentation using the NLST data.
AB  - PURPOSE: To study the variability in volume change estimates of pulmonary nodules
      due to segmentation approaches used across several algorithms and to evaluate
      these effects on the ability to predict nodule malignancy. METHODS: We obtained
      100 patient image datasets from the National Lung Screening Trial (NLST) that had
      a nodule detected on each of two consecutive low dose computed tomography (LDCT)
      scans, with an equal proportion of malignant and benign cases (50 malignant, 50
      benign). Information about the nodule location for the cases was provided by a
      screen capture with a bounding box and its axial location was indicated. Five
      participating quantitative imaging network (QIN) institutions performed nodule
      segmentation using their preferred semi-automated algorithms with no manual
      correction; teams were allowed to provide additional manually corrected
      segmentations (analyzed separately). The teams were asked to provide segmentation
      masks for each nodule at both time points. From these masks, the volume was
      estimated for the nodule at each time point; the change in volume (absolute and
      percent change) across time points was estimated as well. We used the concordance
      correlation coefficient (CCC) to compare the similarity of computed nodule
      volumes (absolute and percent change) across algorithms. We used Logistic
      regression model on the change in volume (absolute change and percent change) of
      the nodules to predict the malignancy status, the area under the receiver
      operating characteristic curve (AUROC) and confidence intervals were reported.
      Because the size of nodules was expected to have a substantial effect on
      segmentation variability, analysis of change in volumes was stratified by lesion
      size, where lesions were grouped into those with a longest diameter of <8 mm and
      those with longest diameter >= 8 mm. RESULTS: We find that segmentation of the
      nodules shows substantial variability across algorithms, with the CCC ranging
      from 0.56 to 0.95 for change in volume (percent change in volume range was [0.15
      to 0.86]) across the nodules. When examining nodules based on their longest
      diameter, we find the CCC had higher values for large nodules with a range of
      [0.54 to 0.93] among the algorithms, while percent change in volume was [0.3 to
      0.95]. Compared to that of smaller nodules which had a range of [-0.0038 to 0.69]
      and percent change in volume was [-0.039 to 0.92]. The malignancy prediction
      results showed fairly consistent results across the institutions, the AUC using
      change in volume ranged from 0.65 to 0.89 (Percent change in volume was 0.64 to
      0.86) for entire nodule range. Prediction improves for large nodule range (>= 8
      mm) with AUC range 0.75 to 0.90 (percent change in volume was 0.74 to 0.92).
      Compared to smaller nodule range (<8 mm) with AUC range 0.57 to 0.78 (percent
      change in volume was 0.59 to 0.77). CONCLUSIONS: We find there is a fairly high
      concordance in the size measurements for larger nodules (>=8 mm) than the lower
      sizes (<8 mm) across algorithms. We find the change in nodule volume (absolute
      and percent change) were consistent predictors of malignancy across institutions,
      despite using different segmentation algorithms. Using volume change estimates
      without corrections shows slightly lower predictability (for two teams).

PMID- 29363775
TI  - Toll-like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of
      autoimmunity?
AB  - Pathogen infections and dysregulated Toll-like receptor (TLR)-mediated innate
      immune responses are suspected to play key roles in autoimmunity. Among TLRs,
      TLR7 and TLR9 have been implicated in several autoimmune conditions, mainly
      because of their ability to promote abnormal B cell activation and survival.
      Recently, we provided evidence of Epstein-Barr virus (EBV) persistence and
      reactivation in the thymus of myasthenia gravis (MG) patients, suggesting an
      involvement of EBV in the intrathymic pathogenesis of the disease. Considerable
      data highlight the existence of pathogenic crosstalk among EBV, TLR7, and TLR9:
      EBV elicits TLR7/9 signaling, which in turn can enhance B cell dysfunction and
      autoimmunity. In this article, after a brief summary of data demonstrating TLR
      activation in MG thymus, we provide an overview on the contribution of TLR7 and
      TLR9 to autoimmune diseases and discuss our recent findings indicating a pivotal
      role for these two receptors, along with EBV, in driving, perpetuating, and/or
      amplifying intrathymic B cell dysregulation and autoimmune responses in MG.
      Development of therapeutic approaches targeting TLR7 and TLR9 signaling could be
      a novel strategy for treating the chronic inflammatory autoimmune process in
      myasthenia gravis.

PMID- 29363777
TI  - Quantitative genetic methods depending on the nature of the phenotypic trait.
AB  - A consequence of the assumptions of the infinitesimal model, one of the most
      important theoretical foundations of quantitative genetics, is that phenotypic
      traits are predicted to be most often normally distributed (so-called Gaussian
      traits). But phenotypic traits, especially those interesting for evolutionary
      biology, might be shaped according to very diverse distributions. Here, I show
      how quantitative genetics tools have been extended to account for a wider
      diversity of phenotypic traits using first the threshold model and then more
      recently using generalized linear mixed models. I explore the assumptions behind
      these models and how they can be used to study the genetics of non-Gaussian
      complex traits. I also comment on three recent methodological advances in
      quantitative genetics that widen our ability to study new kinds of traits: the
      use of "modular" hierarchical modeling (e.g., to study survival in the context of
      capture-recapture approaches for wild populations); the use of aster models to
      study a set of traits with conditional relationships (e.g., life-history traits);
      and, finally, the study of high-dimensional traits, such as gene expression.

PMID- 29363779
TI  - Genetic constraints on adaptation: a theoretical primer for the genomics era.
AB  - Genetic constraints are features of inheritance systems that slow or prohibit
      adaptation. Several population genetic mechanisms of constraint have received
      sustained attention within the field since they were first articulated in the
      early 20th century. This attention is now reflected in a rich, and still growing,
      theoretical literature on the genetic limits to adaptive change. In turn,
      empirical research on constraints has seen a rapid expansion over the last two
      decades in response to changing interests of evolutionary biologists, along with
      new technologies, expanding data sets, and creative analytical approaches that
      blend mathematical modeling with genomics. Indeed, one of the most notable and
      exciting features of recent progress in genetic constraints is the close
      connection between theoretical and empirical research. In this review, we discuss
      five major population genetic contexts of genetic constraint: genetic dominance,
      pleiotropy, fitness trade-offs between types of individuals of a population, sign
      epistasis, and genetic linkage between loci. For each, we outline historical
      antecedents of the theory, specific contexts where constraints manifest, and
      their quantitative consequences for adaptation. From each of these theoretical
      foundations, we discuss recent empirical approaches for identifying and
      characterizing genetic constraints, each grounded and motivated by this theory,
      and outline promising areas for future work.

PMID- 29363780
TI  - Kangaroo Mother Care in Colombia: A Subaltern Health Innovation against For
      profit Biomedicine.
AB  - This ethnographic study presents the origins, growth, and collapse of the first
      Kangaroo Mother Care (KMC) program, a well-established practice for neonatal care
      created in 1978 in Colombia. The WHO and UNICEF praised this zero-cost
      revolutionary technique for its promotion of skin-to-skin contact between
      premature and low-birth-weight newborns and family members. KMC facilitates early
      hospital discharge, brings many clinical and psychological benefits, and
      constitutes an excellent alternative to placing babies in incubators. However,
      these benefits and political potential against biomedical interventions were
      undermined after being relabeled as a "reverse innovation," a business concept
      that encourages corporate investments in low-income countries to develop
      technologies that can both solve global health problems and boost multinational
      corporations profits. In response, I propose "subaltern health innovations" as a
      label for KMC that accounts for the power dynamics in global health between
      health care initiatives that originate in the Global South and neoliberal
      configurations of for-profit biomedicine.

PMID- 29363776
TI  - Gene regulatory mechanisms underlying sex differences in brain development and
      psychiatric disease.
AB  - The sexual differentiation of the mammalian nervous system requires the precise
      coordination of the temporal and spatial regulation of gene expression in diverse
      cell types. Sex hormones act at multiple developmental time points to specify sex
      typical differentiation during embryonic and early development and to coordinate
      subsequent responses to gonadal hormones later in life by establishing sex
      typical patterns of epigenetic modifications across the genome. Thus, mutations
      associated with neuropsychiatric conditions may result in sexually dimorphic
      symptoms by acting on different neural substrates or chromatin landscapes in
      males and females. Finally, as stress hormone signaling may directly alter the
      molecular machinery that interacts with sex hormone receptors to regulate gene
      expression, the contribution of chronic stress to the pathogenesis or
      presentation of mental illness may be additionally different between the sexes.
      Here, we review the mechanisms that contribute to sexual differentiation in the
      mammalian nervous system and consider some of the implications of these processes
      for sex differences in neuropsychiatric conditions.

PMID- 29363778
TI  - Mechanisms Underlying Chronic Binge Alcohol Exposure-Induced Uterine Artery
      Dysfunction in Pregnant Rat.
AB  - BACKGROUND: A cardinal feature of fetal alcohol syndrome is growth restriction.
      Maternal uterine artery adaptations to pregnancy correlate with birthweight and
      survival. We hypothesized that gestational binge alcohol exposure impairs
      maternal uterine vascular function, affecting endothelial nitric oxide (NO)
      mediated vasodilation. METHODS: Pregnant rats grouped as pair-fed control or
      binge alcohol exposed received a once-daily, orogastric gavage of isocaloric
      maltose-dextrin or alcohol, respectively. On gestational day 20, primary uterine
      arteries were isolated, cannulated, and connected to a pressure transducer, and
      functional studies were conducted by dual-chamber arteriography. Uterine arteries
      maintained at constant intramural pressure (90 mm Hg) were maximally constricted
      with thromboxane, and a dose-response for acetylcholine (Ach) was recorded.
      RESULTS: The alcohol group exhibited significantly impaired endothelium
      dependent, Ach-induced uterine artery relaxation (?~30%). Subsequently, a dose
      response was recorded following inhibition of endothelium-derived hyperpolarizing
      factor (apamin and TRAM-34) and prostacyclin (indomethacin). Ach-induced
      relaxation in the pair-fed control decreased by ~46%, and interestingly,
      relaxation in alcohol group further decreased by an additional ~48%,
      demonstrating that gestational binge alcohol impairs the NO system in the primary
      uterine artery. An endothelium-independent sodium nitroprusside effect was not
      observed. Immunoblotting indicated that alcohol decreased the level of
      endothelial excitatory P-Ser1177 endothelial NO synthase (eNOS) (p < 0.05) and
      total eNOS expression (p < 0.05) compared to both the normal and pair-fed
      controls. P-Ser1177 eNOS level was also confirmed by immunofluorescence imaging.
      CONCLUSIONS: This is the first study to demonstrate maternal binge alcohol
      consumption during pregnancy disrupts uterine artery vascular function via
      impairment of the eNOS vasodilatory system.

PMID- 29363781
TI  - Advanced Hemophilic Arthropathy: Sensitivity of Soft Tissue Discrimination With
      Musculoskeletal Ultrasound.
AB  - OBJECTIVES: Point-of-care musculoskeletal ultrasound (US) is increasingly used by
      hemophilia providers to guide management; however, pathologic tissue
      differentiation with US is uncertain. We sought to determine the extent to which
      point-of-care musculoskeletal US can identify and discriminate pathologic soft
      tissue changes in hemophilic arthropathy. METHODS: Thirty-six adult patients with
      hemophilia A/B were prospectively enrolled. Point-of-care musculoskeletal US
      examinations were performed on arthropathic joints (16 knees, 10 ankles, and 10
      elbows) using standard views by a musculoskeletal US-trained and certified
      hematologist, who recorded abnormal intra-articular soft tissue accumulation.
      Within 3 days, magnetic resonance imaging was performed using conventional and
      multiecho ultrashort echo time sequences. Soft tissue identification (synovial
      proliferation with or without hemosiderin, fat, and/or blood products) was
      performed by a musculoskeletal radiologist. Findings obtained with both imaging
      modalities were compared and correlated in a blinded fashion. RESULTS: There was
      perfect agreement between the modalities on the presence of abnormal soft tissue
      (34 of 36 cases). However, musculoskeletal US was unable to discriminate between
      coagulated blood, synovium, intrasynovial or extrasynovial fat tissue, or
      hemosiderin deposits because of wide variations in echogenicity. CONCLUSIONS:
      Musculoskeletal US is valuable for point-of-care imaging to determine the
      presence of soft tissue accumulation in discrete areas. However, because of
      limitations of musculoskeletal US in discriminating the nature of pathologic soft
      tissues and detecting hemosiderin, magnetic resonance imaging will be required if
      such discrimination is clinically important.

PMID- 29363782
TI  - Osteogenic and osteoclastogenic potential of jaw bone-derived cells-A case study.
AB  - Though the stem cell properties of tooth-derived periodontal ligament and
      gingival cells have been widely documented, surprisingly little is known about
      both the osteogenic and osteoclastogenic differentiation capacities of the more
      clinically relevant jaw bone-derived cells. These cells could be considered being
      recruited during bone healing such as after tooth extraction, after placing an
      implant, or after surgical or traumatic injury. Here, we compared the osteoblast
      and osteoclastogenesis features of four consecutive bone outgrowths with
      periodontal ligament and gingiva cells. For osteogenesis assay, cells were
      cultured in osteogenic medium, whereas in osteoclastogenesis assays, cells were
      cultured in the presence of human peripheral blood mononuclear cells (PBMCs) as a
      source of osteoclast precursors. After osteogenic stimulus, all six cell types
      responded by an increased expression of osteoblast markers RUNX2 and DMP1.
      Periodontal ligament cells expressed significantly higher levels of RUNX2
      compared to all bone outgrowths. Alkaline phosphatase enzyme levels in
      periodontal ligament cells reached earlier and higher peak expression. Mineral
      deposits were highest in periodontal ligament, gingiva and the first bone
      outgrowth. Osteoclastogenesis revealed a stepwise increase of secreted pro
      osteoclastogenesis proteins M-CSF, IL-1beta, and TNF-alpha in the last three
      consecutive bone cultures. OPG mRNA showed the opposite: high expression in
      periodontal and gingiva cells and the first outgrowth. Osteoclast numbers were
      similar between the six cultures, both on bone and on plastic. This first study
      reveals that jaw bone outgrowths contain bone remodelling features that are
      slightly different from tooth-associated cells.

PMID- 29363783
TI  - Long noncoding RNA NEAT1-modualted miR-506 regulates gastric cancer development
      through targeting STAT3.
AB  - Accumulating evidence has indicated that lncRNA NEAT1 exerts critical roles in
      cancers. So far, the detailed biological role and mechanisms of NEAT1 which are
      responsible for human gastric cancer (GC) is still largely unknown. Here, we
      observed that NEAT1 and STAT3 expression were significantly upregulated in human
      gastric cancer cells including BGC823, SGC-7901, AGS, MGC803 and MKN28 cells
      compared to normal gastric epithelial cells GES-1 while miR-506 was
      downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to
      repress the growth, migration and invasion of gastric cancer cells. Reversely,
      overexpression of NEAT1 exhibited an increase ability of gastric cancer
      progression in BGC823 and SGC-7901 cells. Bioinformatics analysis, dual
      luciferase reporter assays, RIP assays and RNA pull-down tests validated the
      negative binding correlation between NEAT1 and miR-506. In addition, it was found
      that miR-506 can modulate expression of NEAT1 in vitro. STAT3 was predicted as an
      mRNA target of miR-506 and miR-506 mimics can suppress STAT3 mRNA expression.
      Subsequently, it was observed that downregulation of NEAT1 can restrain gastric
      cancer development by decreasing STAT3 which can be reversed by miR-506
      inhibitors. Therefore, it was hypothesized in our study that NEAT1 can be
      recognized as a ceRNA to modulate STAT3 by sponging miR-506 in gastric cancer. In
      conclusion, we implied that NEAT1 can serve as an important biomarker in gastric
      cancer diagnosis and treatment. This article is protected by copyright. All
      rights reserved.

PMID- 29363784
TI  - Nutraceuticals in the management of patients with statin-associated muscle
      symptoms, with a note on real-world experience.
AB  - There is considerable evidence for the role of low-density lipoprotein
      cholesterol (LDL-C) in the development of atherosclerotic cardiovascular disease.
      Although statin therapy remains the most frequency prescribed medication to
      reduce LDL-C and lower risk of cardiovascular disease, a considerable number of
      patients develop muscle-related side affects. This review summarizes recent
      literature supporting the role of nutraceuticals as LDL-C-lowering therapy in
      statin-intolerant patients, with evidence from our own clinical practices.

PMID- 29363786
TI  - Comparative evaluation of five protocols for protein extraction from stony corals
      (Scleractinia) for proteomics.
AB  - Corals especially the reef-building species are very important to marine
      ecosystems. Proteomics has been used for researches on coral diseases, bleaching
      and responses to the environment change. A robust and versatile protein
      extraction protocol is required for coral proteomics. However, a comparative
      evaluation of different protein extraction protocols is still not available for
      proteomic analysis of stony corals. In the present study, five protocols were
      compared for protein extraction from stony corals. The five protocols were
      TRIzol, phenol-based extraction (PBE), trichloroacetic acid (TCA)-acetone, glass
      bead-assisted extraction (GBAE) and a commercially available kit. PBE, TRIzol and
      the commercial kit were more robust for extracting proteins from stony corals.
      The protein extraction efficiency and repeatability, two dimensional
      electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of
      flight mass spectrometry (MALDI TOF MS) were employed to evaluate the protocols.
      The results indicated that PBE protocol had the better protein extraction
      efficiency than the others. Protein extraction coverage varied among the
      procedures. Each protocol favored for certain proteins. Therefore, it is very
      important for coral proteomic analysis to select a suitable protein protocol upon
      the experimental design. In general, PBE protocol can be the first choice for
      extracting proteins from stony corals.

PMID- 29363785
TI  - Revisiting the genomic hypomethylation hypothesis of aging.
AB  - The genomic hypomethylation hypothesis of aging proposes that an overall decrease
      in global DNA methylation occurs with age, and it has been argued that the
      decrease in global DNA methylation could be an important factor in aging,
      resulting in the relaxation of gene expression regulation and abnormal gene
      expression. Since it was initially observed that DNA methylation decreased with
      age in 1974, 16 articles have been published describing the effect of age on
      global DNA methylation in various tissues from rodents and humans. We critically
      reviewed the publications on the effect of age on DNA methylation and the
      expression of the enzymes involved in DNA methylation to evaluate the validity of
      the hypomethylation hypothesis of aging. On the basis of the current scientific
      literature, we conclude that a decrease in the global methylation of the genome
      occurs in most if not all tissues/cells as an animal ages. However, age-related
      changes in DNA methylation in specific regions or at specific sites in the genome
      occur even though the global DNA methylation does not change.

PMID- 29363788
TI  - Evaluation of the Anterior Talofibular Ligament via Stress Sonography in
      Asymptomatic and Symptomatic Populations.
AB  - OBJECTIVES: Sonography during externally applied stress has the potential to
      identify ligamentous instability, but diagnostic parameters for the most commonly
      sprained ankle ligament, the anterior talofibular ligament (ATFL), have not yet
      been established. The purpose of this study was to determine normative values of
      the change in the length of the ATFL in an asymptomatic population during manual
      stress sonography and to compare these values to those in patients with clinical
      findings of anterolateral ankle instability. METHODS: Sonography of the ATFL at
      rest and with maximally applied manual stress was performed bilaterally in 20
      asymptomatic volunteers from each of three 10-year age groups from 20 to 50
      years. Data were compared to those for 34 patients retrospectively identified who
      underwent stress sonography of the ATFL for clinical signs and symptoms of
      chronic anterolateral ankle instability. RESULTS: In the asymptomatic population
      (10 men and 10 women), for men, the mean change in ATFL length between stress and
      neutral positions was 0.44 mm (95% confidence interval [CI], 0.32-0.57 mm). For
      women, it was 0.43 mm (95% CI, 0.31-0.55 mm). The difference in laxity between
      sexes was not significant (P = .85). In the symptomatic population, the mean ATFL
      length difference between stress and neutral positions was 1.26 mm (95% CI, 0.97
      1.55 mm). A t test comparing the mean change in ATFL length showed a
      statistically significant increase in laxity in the symptomatic group (P <
      .0001). CONCLUSIONS: The normal ATFL shows minimal laxity in both men and women
      on stress sonography, with significantly greater laxity among patients with ankle
      instability. Given these findings, stress sonography may have an important role
      in the imaging diagnosis of anterolateral ankle instability.

PMID- 29363787
TI  - A genome-scale DNA methylation study in women with interstitial cystitis/bladder
      pain syndrome.
AB  - AIMS: To assess the feasibility of using voided urine samples to perform a DNA
      methylation study in females with interstitial cystitis/bladder pain syndrome
      (IC/BPS) as compared to age- and race-matched controls. A unique methylation
      profile could lead to a non-invasive, reproducible, and objective biomarker that
      would aid clinicians in the diagnosis of IC/BPS. METHODS: Nineteen IC/BPS
      patients and 17 controls were included. IC/BPS patients had an Interstitial
      Cystitis Symptom Index score of >8; controls had no bladder symptoms. DNA was
      extracted from pelleted urine sediment. Samples with >500 ng of genomic DNA
      underwent quantitative DNA methylation assessment using the Illumina Infinium
      MethylationEPIC BeadChip. Age- and race-matching was applied prior to analysis.
      Linear regression models were used to compare average methylation between IC/BPS
      cases and controls at each cytosine guanine dinucleotide site (loci where
      methylation can occur). RESULTS: Sixteen participants (eight IC/BPS age- and race
      matched to eight controls) had adequate DNA for methylation analysis. The median
      age was 43.5 years (interquartile range 33.8, 65.0), the median BMI was 27.1 (IQR
      22.7, 31.4), and 14 were Caucasian (87.5%). A total of 688 417 CpG sites were
      analyzed. In exploratory pathway analysis utilizing the top 1000 differentially
      methylated CpG sites, the mitogen-activated protein kinase (MAPK) pathway was
      overrepresented by member genes. CONCLUSIONS: The results demonstrate the
      feasibility of using voided urine specimens from women with IC/BPS to perform DNA
      methylation assessments. Additionally, the data suggest genes within or
      downstream of the MAPK pathway exhibit altered methylation in IC/BPS.

PMID- 29363789
TI  - Sertoli cell specific decline in NOR-1 leads to germ cell apoptosis and reduced
      fertility.
AB  - The somatic component of seminiferous epithelium, the Sertoli cells (Sc) respond
      to Follicle stimulating hormone (FSH), and Testosterone (T) to produce factors
      which are necessary for germ cell (Gc) survival and differentiation. Infant Sc do
      not support spermatogenesis in spite of sufficient hormonal milieu, a situation
      similar to that found in male idiopathic infertility. Sc maturation during
      pubertal period involves expression of some genes which may be important for
      initiation of spermatogenesis. Analysis of differentially expressed genes, one by
      one, in infant and pubertal Sc might provide useful information about the
      regulation of spermatogenesis. DNA microarray based analysis of mRNA from 5-days
      (infant) and 12-days (pubertal) old rat Sc revealed increased expression of Nor-1
      by pubertal Sc. NOR-1 is an orphan nuclear receptor involved in maintaining
      cellular homeostasis and disease. We generated transgenic mice using shRNA cloned
      under Pem (Rhox5) promoter which is activated at puberty in Sc. Such transgenic
      mice had reduced Nor-1 expression and increased Tgfbeta1, Tgfbeta3, and Smad3
      expression. Moreover, an increase in beta-catenin expression was observed in NOR
      1 knockdown testes. High beta-catenin in such transgenic mice was found to be
      associated with disruption of Sc maturation characterized by elevated expression
      of Anti Mullerian hormone, Cytokeratin 18, and Sox9. This disruption of Sc
      maturation resulted in Gc apoptosis. Such NOR-1 knockdown mice showed reduced
      sperm count and litter size. We report for the first time that NOR-1 plays a
      crucial role in regulating sperm count and male fertility.

PMID- 29363790
TI  - Linoleic acid induces an increased response to insulin in MDA-MB-231 breast
      cancer cells.
AB  - Epidemiological studies and animal models suggest a link between high levels of
      dietary fat intake and an increased risk of developing breast cancer.
      Hyperinsulinemia is a feature of obesity, diabetes, and metabolic syndrome that
      is associated with an increased breast cancer risk. Insulin is a hormone involved
      in metabolic regulation of carbohydrate. However, it is also a growth factor that
      mediates proliferation and migration. Linoleic acid (LA) is a fatty acid that
      induces migration and invasion in breast cancer cells. In the present study, we
      demonstrate, for the first time, that treatment with LA increases IR and IGF1R
      expression through a Free Fatty Acid Receptor 4 (FFAR4)-, lipooxygenases (LOXs)-,
      and SRC-dependent pathway in MDA-MB-231 breast cancer cells, and similarly
      induces an increase of IR expression in MCF-7 breast cancer cells. In addition,
      insulin induces tyrosine phosphorylation of IR/IGF1R and migration in MDA-MB-231
      cells pretreated with LA, whereas it augments the increase in migration in MCF-7
      cells pretreated with LA. Pretreatment of MDA-MB-231 cells with LA induces
      invasion, proliferation, and increase the MMP-9 secretion induced by insulin. In
      summary, our findings demonstrate that treatment with LA induces a higher
      response to insulin in breast cancer cells.

PMID- 29363791
TI  - Whey protein isolate with improved film properties through cross-linking
      catalyzed by small laccase from Streptomyces coelicolor.
AB  - BACKGROUND: The effects of small laccase (SLAC) from Streptomyces coelicolor on
      the properties of whey protein isolate (WPI) films were studied. RESULTS: WPI was
      catalyze by SLAC without phenolic acid assistance. Particle size distribution
      results showed that some complexes with higher relative molecular weight formed
      in WPI samples treated with SLAC. The content of alpha-helixes decreased while
      those of beta-sheets and random coils increased following SLAC treatment
      according to circular dichroism results. Fourier transform infrared spectral
      analysis suggested that some conformational changes occurred in WPI following
      SLAC treatment. Analysis of WPI films prepared by casting after SLAC treatment
      indicated that their film properties were all improved, including mechanical
      properties, solubility, water vapor, oxygen and carbon dioxide barrier
      properties, film color, light transmission, transparency and thermal properties.
      Compared with that of the control film, some obvious differences in the
      morphology of the WPI films were observed following SLAC treatment. This report
      demonstrates that laccase can directly catalyze protein cross-linking, which may
      be useful to improve the performance of protein films. CONCLUSION: In this study,
      SLAC was applied to WPI edible film during the film-making process. The results
      showed that SLAC can catalyze WPI cross-linking without phenolic acid assistance,
      and WPI film properties were improved after SLAC treatment. (c) 2018 Society of
      Chemical Industry.

PMID- 29363792
TI  - The efficacy of botulinum toxin A and sacral neuromodulation in the management of
      interstitial cystitis (IC)/bladder pain syndrome (BPS), what do we know? ICI-RS
      2017 think thank, Bristol.
AB  - AIMS: This manuscript aims to address the evidence availale in the literature on
      the efficacy of Botulinum Toxin A (BoNT-A) and sacral neuromodulation (SNM) in
      patients suffering from Interstitial Cystitis (IC)/BPS and propose further
      research to identify mechanisms of action and establish the clinical efficacy of
      either therapy. METHODS: At the International Consultation on Incontinence
      Research Society (ICI-RS) in 2017, a panel of Functional Urologists and
      Urogynaecologists participated in a Think Tank (TT) discussing the management of
      IC/BPS by BoNT-A and SNM, using available data from both PubMed and Medicine
      literature searches. RESULTS: The role of BoNT-A and SNM in the treatment of
      IC/BPS are discussed and mechanisms of actions are proposed. Despite the
      available randomized trial data on the effect of intravesical BoNT-A treatment on
      symptoms of IC/BPS, a consistent conclusion of a positive effect cannot be drawn
      at the moment, as the published studies are small and heterogeneous in design.
      There is substantive evidence for the positive effects of SNM on symptoms of
      IC/BPS patients however, during patient selection, it is important to distinguish
      the degree and the location of pain in order to tailor the best therapy to the
      right patients. CONCLUSIONS: Both intravesical BoNT-A treatment and SNM have been
      shown to have positive effects in patients with IC/BPS. However, firm conclusions
      cannot yet be drawn. Patient-reported outcomes and quality of life should be
      assessed in addition to urinary and pain symptoms. Since current treatments
      mainly focus on symptomatic relief, future research should also focus on
      clarifying the pathogenic mechanisms involved in IC/BPS.

PMID- 29363793
TI  - Signature microRNAs of nuclear Sm complex associated with breast cancer
      tumorigenesis.
AB  - It is well known that Sm proteins, small nuclear ribonucleoproteins, act as core
      spliceosomal factors in alternative splicing of mRNA precursors. MicroRNAs
      (miRNAs) can function in alternative splicing by targeting mRNAs of splicing
      factors. However, the direct interaction between miRNAs and proteins of splicing
      complex in nucleus has not been explored. In this study, the mature miRNAs in
      nuclear Sm complex of breast cancer cells and normal breast epithelial cells were
      characterized. Small RNA sequencing of immunoprecipitated nuclear Sm complex with
      the SmD1-specific antibody identified 123 and 170 mature miRNAs in nuclear Sm
      complex of normal breast cells and breast cancer cells, respectively. The results
      of Northern blot analysis confirmed the existence of mature miRNAs in Sm complex
      and electrophoretic mobility shift assay (EMSA) validated the binding of miRNAs
      with proteins of Sm complex. Among the identified miRNAs bound to the Sm complex
      in nucleus, 94 miRNAs were significantly upregulated, and 39 miRNAs significantly
      downregulated in breast cancer cells compared with normal breast cells,
      suggesting that miRNAs in nuclear Sm complex might be associated to tumorigenesis
      of breast cancer by regulating Sm complex during alternative splicing of mRNA
      precursors. Our study provided novel clues to reveal the regulatory mechanism of
      Sm complex in the assembly of spliceosome and contributed novel aspects of miRNAs
      to tumorigenesis of breast cancer.

PMID- 29363794
TI  - Distinctive inhibition of alkaline phosphatase isozymes by thiazol-2-ylidene
      benzamide derivatives: Functional insights into their anticancer role.
AB  - In the recent years, the role of alkaline phosphatase (AP) isozymes in the cause
      of neoplastic diseases such as breast, liver, renal, and bone cancer has been
      confirmed and, thus they represent a novel target for the discovery of anticancer
      drugs. In this study different derivatives of thiazol-2-ylidene-benzamide were
      evaluated for their potential to inhibit alkaline phosphatase (AP) isozymes.
      Their anticancer potential was assessed using human breast cancer (MCF-7), bone
      marrow cancer (K-562), and cervical cancer (HeLa) cell lines in comparison to
      normal cells from baby hamster kidney BHK-21. The results suggested that in
      comparison to other derivatives, compounds 2i, 2e, and 2a showed more sensitivity
      towards human tissue non-specific alkaline phosphatase (h-TNAP). Among these, 2"
      chloro-N-(3-(4'-fluorophenyl)-4-methylthiazol-2(3H)-ylidene) benzamide (2e) was
      found as the most potent and selective inhibitor for h-TNAP with an IC50 value of
      0.079 +/- 0.002 MUM. Moreover, a significant correlation was observed between the
      enzyme inhibition profile and cytotoxic data. The compounds exhibiting maximum
      anticancer potential also induced maximum apoptosis in the respective cell lines.
      Furthermore, the DNA interaction studies exhibited the non-covalent mode of
      interaction with the herring sperm-DNA. Molecular docking studies also supported
      the in vitro inhibitory activity of potent compounds. Our findings suggested that
      potent and selective inhibitors might be useful candidates for the treatment or
      prevention of those diseases associated with the higher level of AP. Moreover,
      the study can be useful for the researcher to explore more molecular mechanisms
      of such derivatives and their analogues with the exact findings.

PMID- 29363795
TI  - Financial consequences from smoking-related diseases in middle-income countries:
      Evidence and lessons from Mexico.

PMID- 29363796
TI  - Long-term impacts of hemodialysis on the right ventricle: Assessment via 3
      dimensional speckle-tracking echocardiography.
AB  - BACKGROUND: Right ventricular (RV) dysfunction is a major cause of death in
      patients undergoing maintenance hemodialysis (MHD). We used 3-dimensional speckle
      tracking echocardiography (3DSTE) to evaluate long-term impacts of MHD on RV
      function. HYPOTHESIS: In this study, RV dysfunction in MHD patients will be
      revealed and studied in depth by 3DSTE. METHODS: Echocardiography was performed
      on 110 consecutively enrolled individuals: 30 controls and 80 patients with MHD.
      Conventional echocardiographic parameters and 3DSTE parameters were obtained and
      compared between groups. Univariate and multivariate logistic regression analysis
      identified independent predictors of intradialytic hypotension (IDH). RESULTS:
      Compared with the control group, RV end-diastolic volume (RVEDV) was markedly
      enlarged (46.1 +/- 11.8 mL/m2 vs 42.3 +/- 8.6 mL/m2 ; P = 0.047), whereas RV
      ejection fraction (RVEF) was significantly lower in the MHD group (50.6% +/- 5.8%
      vs 55.2% +/- 3.7%; P < 0.001). RV global, septal, and lateral wall longitudinal
      strains were also decreased in the MHD group (-18.2 +/- 3.6 vs -22.6 +/- 4.3%; 
      13.1 +/- 3.8 vs -17.5 +/- 5.5%; and -23.4 +/- 4.7 vs -27.7 +/- 4.0%,
      respectively; all P < 0.001). RVEF (odds ratio [OR]: 0.72, 95% confidence
      interval [CI]: 0.51 to 1.01, P = 0.038) and history of diabetes (OR: 11.14, 95%
      CI: 1.16 to 106.71, P = 0.036) were 2 independent predictors of IDH.
      Ultrafiltration rate was an independent factor associated with RVEF (beta = 
      0.01, 95% CI: -0.019 to 0.001, P = 0.039). CONCLUSIONS: RVEF by 3DSTE could be an
      important predictor of IDH in MHD patients, and lower ultrafiltration rate was
      protective for RVEF. 3DSTE may have potential in RV evaluation and risk
      stratification in MHD patients.

PMID- 29363799
TI  - Competition in the Health Care Sector: Ten Years Later (Book).

PMID- 29363798
TI  - Evolution of Structural DNA Nanotechnology.
AB  - The research field entitled structural DNA nanotechnology emerged in the
      beginning of the 1980s as the first immobile synthetic nucleic acid junctions
      were postulated and demonstrated. Since then, the field has taken huge leaps
      toward advanced applications, especially during the past decade. This Progress
      Report summarizes how the controllable, custom, and accurate nanostructures have
      recently evolved together with powerful design and simulation software.
      Simultaneously they have provided a significant expansion of the shape space of
      the nanostructures. Today, researchers can select the most suitable fabrication
      methods, and design paradigms and software from a variety of options when
      creating unique DNA nanoobjects and shapes for a plethora of implementations in
      materials science, optics, plasmonics, molecular patterning, and nanomedicine.

PMID- 29363797
TI  - Utility of neutralization test for laboratory diagnosis of suspected mumps.
AB  - Mumps is an infectious disease caused by mumps virus (MuV), which belongs to the
      family Paramyxoviridae and genus Rubulavirus. Typical symptoms of mumps include
      fever and swelling of the parotid glands; however, mumps can be asymptomatic.
      Mumps is diagnosed by molecular and serological methods (i.e., PCR and Enzyme
      Immunoassay [EIA]); however, both methods have pros and cons. This study was
      performed to compare the diagnostic utility of a focus reduction neutralization
      test (FRNT) to that of MuV-specific commercial IgM and IgG antibody EIA in
      patients suspected of having mumps. One hundred-eighty six samples collected
      during mumps outbreak in 2012-16 were studied. Samples (n = 80) were tested by
      all the three serological assays and showed 70.4%, 83% and 92.5% positivity by
      IgM EIA, IgG and FRNT, respectively. In all, 58.8% samples (n = 47) tested
      positive in all three assays. Concordance between mumps RT-PCR and IgM EIA was
      highest during the first 2-5 days and decreased with increasing time post-onset.
      Mumps FRNT results agreed with those of RT-PCR/IgM EIA from the second week
      onwards, whereas the results of mumps IgG EIA agreed with those of RT-PCR/IgM EIA
      from post-onset days 3-10. These findings suggest the utility of a FRNT for
      laboratory diagnosis of mumps in countries whose populations are not immunized
      against this infection.

PMID- 29363800
TI  - Health Care of the Elderly: An Information Sourcebook (Book).

PMID- 29363802
TI  - New Model Management: Griffiths and the N.H.S./Griffiths and the Nurses: A
      National Survey of CNAs (Book).

PMID- 29363801
TI  - Smoking in pregnancy: smokescreen or risk factor? Towards a materialist analysis.
AB  - This paper considers the topic of women's smoking in pregnancy within the general
      context of the current health promotion concern about smoking as a public health
      issue. Drawing on data from an ongoing research project which is investigating
      the interrelationships between'risk', social support and reproductive health, the
      paper argues that smoking in pregnancy constitutes an area of women's behaviour
      which is linked in systematic ways with aspects of their material and social
      position. Consequently, conventional individualist models of smoking behaviour
      both fail to explain why pregnant women smoke and are unable adequately to
      account for the health consequences of this behaviour. The reason for singling
      out smoking in this analysis inheres not in any detrimental health effect
      directly attributable to it, but rather to the way in which pregnancy smoking has
      been socially constructed as a reprehensible feature of women's life-styles.

PMID- 29363803
TI  - Health Care for an Aging Society, Cost-conscious Community Care and Self-Care
      Approaches (Book).

PMID- 29363804
TI  - Task, Talk, and Text in the Operating Room: A Study in Medical Discourse (vol
      XXXIII in Advances in Discourse Processes) (Book).

PMID- 29363805
TI  - Social Order/Mental Disorder: Anglo-American Psychiatry in Historical Perspective
      (Book).

PMID- 29363806
TI  - The Quarterback Speaks to His God (Book).

PMID- 29363807
TI  - Nursing the Dying (Book).

PMID- 29363809
TI  - Sickness as a dominant symbol in life course transitions: an illustrated
      theoretical framework.
AB  - The paper examines how sickness as a cultural performance might be analysed as a
      dominant symbol within life course transitions. The concept of dominant symbol is
      taken from Victor Turner's framework for Symbolic Processual Analysis in ritual
      and pilgrimage and is used to interrogate data collected in an ethnographic study
      of sickness absence in an English primary school. It is suggested that sickness
      played a central part in the construction of meaning around the transition from
      primary to secondary school. The performance of sickness seemed to condense
      ideological features (especially those of gender and work discipline) and to
      express modulations in the meaning of the transition in its different phases. The
      concept of dominant symbol (and the related notion of liminality) illuminate
      these data but need modification to take account of the unritualised and
      fragmented character of many life course transitions in contemporary Western
      societies. It is suggested that with modification these concepts might be applied
      to the meaning of sickness in other life course transitions.

PMID- 29363810
TI  - The Voluntary Impulse. Philanthropy in Modern Britain (Book).

PMID- 29363811
TI  - One Foot in Eden: A Sociological Study of the Range of Therapeutic Community
      Practice/The Therapeutic Community Movement: Charisma and Routinization (Book).

PMID- 29363812
TI  - The Politics of Health in India (Book).

PMID- 29363813
TI  - Author.

PMID- 29363815
TI  - From Population to People (Book).

PMID- 29363814
TI  - Knowledge of shadows: the introduction of X-ray images in medicine.
AB  - Ever since the discovery of X-rays in 1895, X-ray imaging has played a large role
      in the cognitive and practical organization of medicine. This article analyses
      the way X-ray images were introduced and made sense of in medical thinking and
      acting around the turn of the century. The implicit assumption in many histories
      of radiology is that the specific (diagnostic) message of the X-ray images
      resided inside them from the beginning, and that it is obscured either by
      technological or epistemological problems. These being solved, it would then be
      no problem to see directly what information the image contains. In this article
      this assumption is contested. It is argued that the specific content of the
      images was shaped by the activities of X-ray workers within the context of
      medical developments of the time. This shaping, as it is historically
      reconstructed here, consisted of four methods. X-ray workers (be they physicians,
      technicians or scientists) experimented with the technology, the images, the
      photographic materials and the objects that were X-rayed. They used X-ray images
      of dead bodies to compare them with radiographs of living patients. Radiologists
      tried to'translate'diagnostic information acquired with other methods into the
      shadows of the X-ray images. And finally they compared images with images. The
      process of shaping the content and use of X-ray images, of making them represent
      reality, took place within specific institutions, and it took a different form in
      different countries, but also for different parts of the body. Developments of
      institutionalisation and professionalisation of radiology in England and the
      Netherlands are presented to provide a small part of the background of this
      shaping of knowledge of shadows.

PMID- 29363816
TI  - The Social Organization of Death: Medical Discourse and Social Practices in
      Belfast (Book).

PMID- 29363817
TI  - Brachial Artery Wall Stiffness Assessment by Shear Wave Elastography: A Promising
      New Diagnostic Tool for Endothelial Dysfunction Detection.
AB  - OBJECTIVES: This study was designed to measure the changes in brachial artery
      wall stiffness by shear wave elastography (SWE) and evaluate the accuracy of SWE
      changes for detection of endothelial dysfunction. METHODS: Sixty-five consecutive
      participants (19 patients with atherosclerosis proven by coronary angiography, 16
      healthy young adults, 15 patients with cardiovascular risk factors, and 15
      healthy older adults between 50 and 60 years) were prospectively included in this
      study. They were examined in the same week by SWE, and flow-mediated dilatation
      was evaluated for each patient. RESULTS: The mean flow-mediated dilatation values
      +/- 2 SDs after forearm occlusion were 8.54% +/- 1.4% in healthy young adults,
      7.61% +/- 1.4% in healthy older adults, 5.83% +/- 0.7% in patients with risk
      factors (P < .001), and 3.81% +/- 2.4% in patients with atherosclerosis (P <
      .001, with respect to the risk factor group). There was a significant decrease in
      stiffness measurements in parallel with the increase in flow-mediated dilatation:
      19.9% +/- 6.3% in healthy young adults, 16.3% +/- 5.1% in healthy older adults,
      9.8% +/- 5.4% in patients with risk factors (P < .05 with respect to the group
      with no risk factors), and 7.8% +/- 6.4% in patients with atherosclerosis (P <
      .001 with respect to the healthy older adults). CONCLUSIONS: Shear wave
      elastography in combination with flow-mediated dilatation could be a promising,
      widely available noninvasive diagnostic tool for detecting endothelial
      dysfunction.

PMID- 29363818
TI  - Salivary tannin-binding proteins are a pervasive strategy used by the
      folivorous/frugivorous black howler monkey.
AB  - Dietary tannins can affect protein digestion and absorption, be toxic, and
      influence food selection by being astringent and bitter tasting. Animals that
      usually ingest tannins may regularly secrete tannin-binding salivary proteins
      (TBSPs) to counteract the negative effects of tannins or TBSPs production can be
      induced by a tannin-rich diet. In the wild, many primates regularly eat a diet
      that contains tannin-rich leaves and unripe fruit and it has been speculated that
      they have the physiological ability to cope with dietary tannins; however,
      details of their strategy remains unclear. Our research details the salivary
      protein composition of wild and zoo-living black howler monkeys (Alouatta pigra)
      feeding on natural versus manufactured low-tannin diets, and examines differences
      in TBSPs, mainly proline-rich proteins (PRPs), to determine whether production of
      these proteins is dependent on the tannin content of their food. We measured the
      pH, flow rate, and concentration of total protein and trichloroacetic acid
      soluble proteins (an index of PRPs) in saliva. Howler monkeys produced slightly
      alkaline saliva that may aid in the binding interaction between tannin and
      salivary proteins. We used gel electrophoresis to describe the salivary protein
      profile and this analysis along with a tannin-binding assay allowed us to detect
      several TBSPs in all individuals. We found no differences in the characteristics
      of saliva between wild and zoo-living monkeys. Our results suggest that black
      howler monkeys always secrete TBSPs even when fed on foods low in tannins. This
      strategy of constantly using this salivary anti-tannin defense enables them to
      obtain nutrients from plants that sometimes contain high levels of tannins and
      may help immediately to overcome the astringent sensation of their food allowing
      howler monkeys to eat tanniferous plants.

PMID- 29363819
TI  - Oscillating Chiral-Nematic Fingerprints Wipe Away Dust.
AB  - This work presents an approach to create mechanical undulations at a solid
      organic coating surface under the influence of an electric field. The coating is
      fabricated through polymerization of chiral reactive mesogens aligned in their
      fingerprint mode on top of interdigitated electrodes. The fingerprint mode gives
      a corrugation of the surface perpendicular to the helix axes. When a lateral
      alternating electric field is applied, the order parameter of the helicoidally
      packed mesogens is reduced. This simultaneously leads to an inversion of the
      fingerprint heights, an overall thickness increase, and a chaotic and fast
      surface oscillation. These three effects work in concert stimulating wavy
      deformation figures at the coating surface. The process is fast and reversible;
      the dynamics of the topographic textures stop immediately when the electric field
      is switched off. The continuous generation of surface undulations sustains
      transport of species at the coating surface. It removes dust and debris providing
      an active dust control.

PMID- 29363820
TI  - Flavonoid silybin improves the response to radiotherapy in invasive bladder
      cancer.
AB  - Conservative treatment for invasive bladder cancer (BC) involves a complete
      transurethral tumor resection combined with chemotherapy (CT) and radiotherapy
      (RT). The major obstacles of chemo-radiotherapy are the addition of the
      toxicities of RT and CT, and the recurrence due to RT and CT resistances. The
      flavonoid Silybin (Sb) inhibits pathways involved in cell survival and resistance
      mechanisms, therefore the purpose of this paper was to study in vitro and in
      vivo, the ability of Sb to improve the response to RT, in two murine BC cell
      lines, with different levels of invasiveness, placing emphasis on radio
      sensitivity, and pathways involved in radio-resistance and survival. In vitro, Sb
      radio-sensitized murine invasive cells through the inhibition of RT-induced NF
      kappaB and PI3K pathways, and the increase of oxidative stress, while non
      invasive cells did not show to be sensitized. In vivo, Sb improved RT-response
      and overall survival in invasive murine tumors. As Sb is already being tested in
      clinical trials for other urological cancers and it improves RT-response in
      invasive BC, these results could have translational relevance, supporting further
      research.

PMID- 29363821
TI  - Daily Assessment of Stressful events and Coping in early post-operative recovery
      after colorectal cancer surgery.
AB  - This study describes the most stressful events and coping strategies used by
      patients with colorectal cancer 4-6 weeks after surgery and whether the coping
      strategies were considered helpful or not. For the investigation of situational
      coping, an exploratory design was used. One hundred and five patients from three
      Swedish hospitals were included to fill in the Daily Coping Assessment. Most
      stressful event, number and types of pre-defined coping strategies used, and if
      the coping strategy used was considered helpful or not, were measured for 5 days.
      Of 523 diary entries, 180 reported no stressful events. The most stressful event,
      also with worst level of control and expectation, was "Pain," followed by
      "Nausea/vomiting." The areas causing most stressful events were "Bowel-related"
      and "Surgery and treatment-related problems." Acceptance and Direct action were
      the most frequently used coping strategies. There was a wide range of perceived
      helpfulness if coping strategies were placed in relation to specific areas of
      events. The conclusion was that patients revealed several strategies for coping
      with stressful events but needed a higher level of preparedness for what might
      come and therefore need to be given appropriate support to cope during the early
      recovery phase. Such support is suggested to be person-centred and oriented
      towards individually adapting standardised regimens, given the variety of
      situations to which the stressful events reported in the study were related.

PMID- 29363822
TI  - Defective Metal-Organic Frameworks.
AB  - The targeted incorporation of defects into crystalline matter allows for the
      manipulation of many properties and has led to relevant discoveries for optimized
      and even novel technological applications of materials. It is therefore exciting
      to see that defects are now recognized to be similarly useful in tailoring
      properties of metal-organic frameworks (MOFs). For instance, heterogeneous
      catalysis crucially depends on the number of active catalytic sites as well as on
      diffusion limitations. By the incorporation of missing linker and missing node
      defects into MOFs, both parameters can be accessed, improving the catalytic
      properties. Furthermore, the creation of defects allows for adding properties
      such as electronic conductivity, which are inherently absent in the parent MOFs.
      Herein, progress of the rapidly evolving field of the past two years is
      overviewed, putting a focus on properties that are altered by the incorporation
      and even tailoring of defects in MOFs. A brief account is also given on the
      emerging quantitative understanding of defects and heterogeneity in MOFs based on
      scale-bridging computational modeling and simulations.

PMID- 29363823
TI  - Suppressive effects of tenofovir disoproxil fumarate, an antiretroviral prodrug,
      on mineralization and type II and type III sodium-dependent phosphate
      transporters expression in primary human osteoblasts.
AB  - Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug commonly used for
      the management of Human Immunodeficiency Virus (HIV) in highly active
      antiretroviral therapy (HAART) and of chronic Hepatitis B Virus (HBV) infections.
      Long-term TDF-treated subjects present decrease of bone mineral density and
      rarely severe osteomalacia. Although these adverse effects have been attributed
      to the impaired proximal tubule function, a possible direct involvement of TDF on
      osteoblasts should be taken into account. The aim of this study was to evaluate
      whether sodium phosphate transporters NPT2A (sodium-dependent phosphate transport
      protein 2A), NPT2C (sodium-dependent phosphate transport protein 2C), PIT1
      (sodium-dependent phosphate transporter 1), and PIT2 (sodium-dependent phosphate
      transporter 2) were expressed in primary human osteoblasts (HOBs), whether their
      expression was related to HOBs differentiation and whether TDF could affect
      mineralization and gene expression. PIT1 and PIT2 were expressed under
      proliferating conditions and increased after induction of mineralization, while
      NPT2A and NPT2C were almost undetectable. In HOBs TDF exposure induced a
      significant dose-dependent decrease in mineralization. Moreover, TDF caused a
      reduction of COL1A1 and of ATF4 expression in differentiated HOBs. In summary,
      HOBs do not express NPT2A and NPT2C and do express PIT1 and PIT2, suggesting a
      role of these two latter in human osteoblast mineralization. TDF impairs
      osteoblast mineralization, confirming a direct negative effect on bone.
      Therefore, in clinical practice, bone damage must be suspected and evaluated also
      in patients receiving TDF without kidney function alterations.

PMID- 29363824
TI  - Comparison of water and air charged transducer catheter pressures in the
      evaluation of cystometrogram and voiding pressure studies.
AB  - AIMS: Air-charged (AC) and water-perfused (WP) catheters have been evaluated for
      differences in measuring pressures for voiding dysfunction. Typically, a two
      catheter system was used. We believe that simultaneous pressure measurements with
      AC and WP in a single catheter will provide analogous pressures for coughs,
      Valsalvas, and maximum pressures in voiding pressure studies (VPS). METHODS: This
      IRB approved prospective study included 50 women over age 21. AC dual TDOC
      catheters were utilized. The water-filling channel served as the bladder filler
      and the water pressure readings. Patients were evaluated with empty bladders and
      at volumes of 50-100 mL, 200 mL, and maximum capacity with cough and Valsalva
      maneuvers. Comparative analysis was performed on maximum stress peak pressures.
      At maximum bladder capacity, VPS was done and maximum voiding pressure was
      recorded. RESULTS: Comparing coughs and Valsalva maneuvers pressures, there was
      significant increase in variability between AC and WP measurements with less than
      50 mL volume (P < 0.001). Significant correlations were observed between AC and
      WP measurements for coughs and Valsalvas with bladder volume over 50 mL. Visual
      impression showed virtually identical tracings. Cough measurements had an average
      difference of 0.25 cmH2 O (+/-8.81) and Valsalva measurements had an average
      difference of 3.15 cmH2 O (+/-4.72). Thirty-eight women had usable maximum
      voiding pressure measurements and had a strong correlation. CONCLUSIONS:
      Cystometrogram and maximum voiding pressure measurements done with either water
      or air charged catheters will yield similarly accurate results and are
      comparable. Results suggest more variability at low bladder volumes <50 mL.

PMID- 29363825
TI  - Atrial flutter in fetus with immune-mediated complete heart block.

PMID- 29363826
TI  - Unusual course of hyperreactio luteinalis in twin pregnancy complicated by twin
      twin transfusion syndrome.

PMID- 29363827
TI  - A novel two-component system modulates quorum sensing and pathogenicity in
      Burkholderia cenocepacia.
AB  - Quorum sensing (QS) is widely utilized by bacterial pathogens to regulate
      biological functions and pathogenicity. Recent evidence has shown that QS is
      subject to regulatory cascades, especially two-component systems that often
      respond to environmental stimulation. At least two different types of QS systems
      regulate pathogenesis in Burkholderia cenocepacia. However, it remains unclear
      how this bacterial pathogen controls these QS systems. Here, we demonstrate a
      novel two-component system RqpSR (Regulating Quorum sensing and Pathogenicity),
      which plays an important role in modulating QS and pathogenesis in B.
      cenocepacia. We demonstrate strong protein-protein binding affinity between RqpS
      and RqpR. Mutations in rqpS and rqpR exerted overlapping effects on B.
      cenocepacia transcriptomes and phenotypes, including motility, biofilm formation
      and virulence. In trans expression of rqpR rescued the defective phenotypes in
      the rqpS mutant. RqpR controls target gene expression by direct binding to DNA
      promoters, including the cis-2-dodecenoic acid (BDSF) and N-acylhomoserine
      lactone (AHL) signal synthase gene promoters. These findings suggest that the
      RqpSR system strongly modulates physiology by forming a complicated hierarchy
      with QS systems. This type of two-component system appears to be widely
      distributed and coexists with the BDSF QS system in various bacterial species.

PMID- 29363828
TI  - Oriented Nanofibrous Polymer Scaffolds Containing Protein-Loaded Porous Silicon
      Generated by Spray Nebulization.
AB  - Oriented composite nanofibers consisting of porous silicon nanoparticles (pSiNPs)
      embedded in a polycaprolactone or poly(lactide-co-glycolide) matrix are prepared
      by spray nebulization from chloroform solutions using an airbrush. The nanofibers
      can be oriented by an appropriate positioning of the airbrush nozzle, and they
      can direct growth of neurites from rat dorsal root ganglion neurons. When loaded
      with the model protein lysozyme, the pSiNPs allow the generation of nanofiber
      scaffolds that carry and deliver the protein under physiologic conditions
      (phosphate-buffered saline (PBS), at 37  degrees C) for up to 60 d, retaining 75%
      of the enzymatic activity over this time period. The mass loading of protein in
      the pSiNPs is 36%, and in the resulting polymer/pSiNP scaffolds it is 3.6%. The
      use of pSiNPs that display intrinsic photoluminescence (from the quantum-confined
      Si nanostructure) allows the polymer/pSiNP composites to be definitively
      identified and tracked by time-gated photoluminescence imaging. The remarkable
      ability of the pSiNPs to protect the protein payload from denaturation, both
      during processing and for the duration of the long-term aqueous release study,
      establishes a model for the generation of biodegradable nanofiber scaffolds that
      can load and deliver sensitive biologics.

PMID- 29363829
TI  - Genome-wide non-invasive prenatal screening for all cytogenetically visible
      imbalances.

PMID- 29363830
TI  - The Viability of C5-Protonated- and C4,C5-Ditopic Carbanionic Abnormal NHCs: A
      New Dimension in NHC Chemistry.
AB  - The first C5-protonated abnormal N-heterocyclic carbene (aNHC), PhC{N(2,6-iPr2 C6
      H3 )}2 CHC: (4) is readily accessible by C4-deprotonation of [ArC{N(2,6-iPr2 C6
      H3 )}2 CHCH]X (3 a-X) (Ar=Ph, X=Br or I) with a base. The aNHC 4 is stable at 298
      K in [D8 ]THF solution and has been spectroscopically characterized. The facile
      availability of 4 enables the synthesis of a series of main-group compounds as
      well as transition-metal complexes featuring a new phosphorus-aNHC hybrid ligand.
      Double deprotonation of [ArC{N(2,6-iPr2 C6 H3 )}2 CHCH]X (Ar=Ph, 3 a-X (X=Br or
      I); 4-Tol, 3 b-Br; 4-DMP, 3 c-Br; Tol=MeC6 H4 , DMP=Me2 NC6 H4 ) with nBuLi
      yields the C4,C5-ditopic carbanionic aNHCs, [ArC{N(2,6-iPr2 C6 H3 )}2 (C:)2
      ]Li(THF)n (Ar=Ph, 13 a; 4-Tol, 13 b; 4-DMP, 13 c), which on treatment with Ph2
      PCl affords cationic vicinal bisphosphine derivatives [ArC{N(2,6-iPr2 C6 H3 )}2
      {C(PPh2 }2 ]X (Ar=Ph, 14 a-X, X=Br or I; 4-Tol, 14 b-Br; 4-DMP, 14 c-Br).

PMID- 29363831
TI  - Ultrasound diagnosis of endometrial polyps in pregnancy.

PMID- 29363832
TI  - White matter microstructural organisation of interhemispheric pathways predicts
      different stages of bimanual coordination learning in young and older adults.
AB  - The ability to learn new motor skills is crucial for activities of daily living,
      especially in older adults. Previous work in younger adults has indicated fast
      and slow stages for motor learning that were associated with changes in
      functional interactions within and between brain hemispheres. However, the impact
      of the structural scaffolds of these functional interactions on different stages
      of motor learning remains elusive. Using diffusion-weighted imaging and
      probabilistic constrained spherical deconvolution-based tractography, we
      reconstructed transcallosal white matter pathways between the left and right
      primary motor cortices (M1-M1), left dorsal premotor cortex and right primary
      motor cortex (LPMd-RM1) and right dorsal premotor cortex and left primary motor
      cortex (RPMd-LM1) in younger and older adults trained in a set of bimanual
      coordination tasks. We used fractional anisotropy (FA) to assess microstructural
      organisation of the reconstructed white matter pathways. Older adults showed
      lower behavioural performance than younger adults and improved their performance
      more in the fast but less in the slow stage of learning. Linear mixed models
      predicted that individuals with higher FA of M1-M1 pathways improve more in the
      fast but less in the slow stage of bimanual learning. Individuals with higher FA
      of RPMd-LM1 improve more in the slow but less in the fast stage of bimanual
      learning. These predictions did not differ significantly between younger and
      older adults suggesting that, in both younger and older adults, the M1-M1 and
      RPMd-LM1 pathways are important for the fast and slow stage of bimanual learning,
      respectively.

PMID- 29363833
TI  - Purine-related metabolites and their converting enzymes are altered in frontal,
      parietal and temporal cortex at early stages of Alzheimer's disease pathology.
AB  - Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by
      HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine
      deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal
      (FC), parietal (PC) and temporal (TC) cortices at different stages of disease
      progression in Alzheimer's disease (AD) and in age-matched controls.
      Significantly decreased levels of adenosine, guanosine, hypoxanthine and
      xanthine, and apparently less inosine, are found in FC from the early stages of
      AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are
      significantly increased at least at determinate stages of AD whereas hypoxanthine
      and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol
      in FC mainly at early stages but not in PC, and only at advanced stages in
      cytosol in TC. ADA activity is decreased in AD when considered as a whole but
      increased at early stages in TC. Finally, PNP activity is increased only in TC at
      early stages. Purine metabolism alterations occur at early stages of AD
      independently of neurofibrillary tangles and beta-amyloid plaques. Alterations
      are stage dependent and region dependent, the latter showing opposite patterns in
      FC compared with PC and TC. Adenosine is the most affected of the assessed
      purines.

PMID- 29363834
TI  - Body composition and bone mineral density in breast cancer survivors and non
      cancer controls: A 12- to 15-month follow-up.
AB  - While prognosis for breast cancer in women has improved, adverse side effects of
      treatments may negatively affect body composition and bone mineral density (BMD).
      This study assessed body composition and BMD changes in breast cancer survivors
      (BCS) (n = 10, 57.9 +/- 5.7 years) and age-matched women (non-cancer, n = 10,
      56.5 +/- 4.3 years) over a 12- to 15-month period via dual-energy X-ray
      absorptiometry. No differences were observed between groups at baseline except
      forearm BMD values were lower in BCS (BCS: 0.462 +/- 0.070 g/cm2 ; Control: 0.539
      +/- 0.052 g/cm2 , p = .012). Body fat increased in both groups compared to
      baseline (BCS: 38.3-39.6 kg, p = .013; Control: 38.2-39.5 kg, p = .023) at the
      follow-up. Significant decreases in BMD at the lumbar spine, femoral neck, total
      femur and ulna were observed in both groups. Breast cancer survivors had a
      greater decrease in left femoral neck BMD. While BCS demonstrated lower baseline
      forearm BMD values and a greater decrease in left femoral neck BMD, both groups
      showed an increase in body fat and decrease in forearm BMD. These findings
      support the implementation of interventions to improve body composition and BMD
      in both BCS and women without cancer.

PMID- 29363835
TI  - Growth differentiation factor 15 is associated with left atrial/left atrial
      appendage thrombus in patients with nonvalvular atrial fibrillation.
AB  - BACKGROUND: There is evidence suggesting that growth differentiation factor 15
      (GDF-15) appears to be associated with stroke in patients with atrial
      fibrillation (AF). AF-related thromboembolic stroke is predominantly attributed
      to the thrombus from the left atrium (LA) or left atrial appendage (LAA).
      HYPOTHESIS: GDF-15 is related to LA/LAA thrombus in nonvalvular AF (NVAF)
      patients. METHODS: A total of 894 patients with NVAF without anticoagulation
      therapy were included in this study. All patients routinely underwent
      transesophageal echocardiography for detection of LA/LAA thrombus. GDF-15 was
      measured by enzyme-linked immunosorbent assay. Logistic regression models were
      used to test for association. RESULTS: LA/LAA thrombus was detected by
      transesophageal echocardiography in 69 (7.72%) patients with AF. The GDF-15
      levels in the patients with LA/LAA thrombus were significantly higher than those
      without LA/LAA thrombus (log10 GDF-15: 2.989 +/- 0.023 ng/L vs 2.831 +/- 0.007
      ng/L; P < 0.001). Logistic regression analysis showed that GDF-15 was an
      independent risk factor for LA/LAA thrombus (odds ratio [per quarter]: 1.799, 95%
      confidence interval: 1.381-2.344, P < 0.001) after adjusting for potential
      clinical risk factors. The optimal cutoff point for GDF-15 predicting LA/LAA
      thrombus was 809.9 ng/L (sensitivity, 75.3%; specificity, 61.5%), determined by
      ROC curve. The area under the curve was 0.709 (95% confidence interval: 0.644
      0.770, P < 0.001). CONCLUSIONS: Elevated GDF-15 indicated a significantly
      increased risk for LA/LAA thrombus in NVAF patients. Thus, GDF-15 might be a
      potentially useful adjunct in discriminating LA/LAA thrombus in NVAF patients.

PMID- 29363836
TI  - Role of mitochondrial Ca2+ uniporter in remifentanil-induced postoperative
      allodynia.
AB  - Opioid-induced hyperalgesia (OIH) and allodynia is a well-known phenomenon and
      refers to the pain sensitization in patients after prolonged opioid exposure. OIH
      limits the use of opioids in pain control, but the underlying mechanisms are not
      fully clear. This study investigated the role of mitochondrial Ca2+ uniporter
      (MCU) in remifentanil (a commonly used opioid analgesic)-induced allodynia. Using
      a rat model of OIH, we found that incision- and remifentanil-induced mechanical
      allodynia were remarkably attenuated by pretreatment with Ru360, a specific MCU
      antagonist, suggesting a critical role of MCU in both incision- and opioid
      induced allodynia. In addition, imaging studies with Rhod-2 (a mitochondrial Ca2+
      dye) in spinal tissues demonstrated increased mitochondrial Ca2+ level in
      response to incision and remifentanil infusion, which was attenuated by Ru360.
      Western blot and immunohistochemistry showed that pNR [phosphorylated N-methyl-D
      aspartate (NMDA) receptor] and pERK (phosphorylated extracellular signal
      regulated kinase) are increased during both incision-induced hyperalgesia and
      remifentanil-induced hyperalgesia, and again the increases in pNR and pERK were
      remarkably attenuated by Ru360. Together, our data demonstrate that MCU plays a
      critical role in remifentanil-induced postoperative mechanical allodynia, with
      NMDA receptor and ERK as possible downstream effectors. Our findings provide
      novel mechanisms for remifentanil-induced mechanical allodynia and encourage
      future studies to examine the mitochondrial Ca2+ uniporter as a potential
      therapeutic target for prevention of OIH.

PMID- 29363837
TI  - A case series of Acceptance and Commitment Therapy (ACT) for reducing symptom
      interference in functional neurological disorders.
AB  - There is limited high-quality evidence supporting psychological treatments for
      functional neurological disorders (FNDs), and what evidence exists suggests that
      the impact of such treatments could be improved. One way to increase
      effectiveness is to utilize approaches that can have impact across heterogeneous
      FND presentations. Acceptance and Commitment Therapy (ACT) targets a
      transdiagnostic process called psychological flexibility and is used effectively
      to integrate multidisciplinary treatments in other clinical contexts. Here, we
      present a consecutive case series (N = 8) of a relatively brief (6 to 10
      sessions) ACT intervention, delivered face to face by a clinical psychologist in
      an outpatient neuropsychology service. Treatment aimed to reduce symptom
      interference and improve mood via improvements in psychological flexibility.
      Service users presented with a range of FND symptoms (e.g., syncope, limb
      paralysis, and paraesthesia). Following treatment, 5 participants showed reliable
      improvements in symptom interference (Work and Social Adjustment Scale), 2 to the
      extent of clinical significance; 4 had reliable improvements in mood (Clinical
      Outcomes in Routine Evaluation-10), and 2 within the range of clinical
      significance. There were no reliable deteriorations in symptom interference or
      mood. Marked variation was apparent on the measure of psychological flexibility
      (Acceptance and Action Questionnaire II), with 4 reliable improvements, 3 within
      the range of clinical significance, and also 2 reliable deteriorations. These
      promising results suggest that further investigation of an ACT approach to FND is
      warranted. Future studies should include measures of psychological flexibility
      with greater comprehensibility.

PMID- 29363838
TI  - Nitrogen-Coordinated Single Cobalt Atom Catalysts for Oxygen Reduction in Proton
      Exchange Membrane Fuel Cells.
AB  - Due to the Fenton reaction, the presence of Fe and peroxide in electrodes
      generates free radicals causing serious degradation of the organic ionomer and
      the membrane. Pt-free and Fe-free cathode catalysts therefore are urgently needed
      for durable and inexpensive proton exchange membrane fuel cells (PEMFCs). Herein,
      a high-performance nitrogen-coordinated single Co atom catalyst is derived from
      Co-doped metal-organic frameworks (MOFs) through a one-step thermal activation.
      Aberration-corrected electron microscopy combined with X-ray absorption
      spectroscopy virtually verifies the CoN4 coordination at an atomic level in the
      catalysts. Through investigating effects of Co doping contents and thermal
      activation temperature, an atomically Co site dispersed catalyst with optimal
      chemical and structural properties has achieved respectable activity and
      stability for the oxygen reduction reaction (ORR) in challenging acidic media
      (e.g., half-wave potential of 0.80 V vs reversible hydrogen electrode (RHE). The
      performance is comparable to Fe-based catalysts and 60 mV lower than Pt/C -60 MUg
      Pt cm-2 ). Fuel cell tests confirm that catalyst activity and stability can
      translate to high-performance cathodes in PEMFCs. The remarkably enhanced ORR
      performance is attributed to the presence of well-dispersed CoN4 active sites
      embedded in 3D porous MOF-derived carbon particles, omitting any inactive Co
      aggregates.

PMID- 29363839
TI  - A description of 'Australian Lyme disease' epidemiology and impact: an analysis
      of submissions to an Australian senate inquiry.
AB  - BACKGROUND: Many Australian patients are diagnosed and treated for the
      scientifically and politically controversial diagnosis of an endemic form of
      'Australian Lyme Disease'. Patient advocacy led Senator John Madigan to propose
      an Australian Senate Inquiry into this illness. AIM: To describe the symptomology
      and outcomes of patients diagnosed and treated with Lyme disease in Australia.
      METHODS: All public, first-person submissions (n = 698) to the inquiry were
      reviewed and responses analysed for epidemiology, symptoms and impact against
      structured criteria. RESULTS: The most common symptoms described were fatigue
      (62.6%), disordered thinking (51.9%) and sensory disturbance (46.1%). Respondents
      reported experiencing symptoms for a median of 10 years and spent a median of $30
      000 on diagnosis and treatment. Almost 10% of respondents self-diagnosed after
      being exposed to a media report of Australian Lyme disease. CONCLUSIONS: Patients
      diagnosed with Lyme disease in Australia display a symptomology similar to
      'medically unexplained physical symptoms' syndromes, experience social and
      financial harms, and are at risk of nosocomial harms. Negative medical
      interactions and the media may contribute to patients seeking alternative and
      potentially non-evidence-based diagnoses and treatments.

PMID- 29363840
TI  - Silver nanoparticles in sewage sludge: Bioavailability of sulfidized silver to
      the terrestrial isopod Porcellio scaber.
AB  - Silver nanoparticles (AgNPs) are efficiently converted during the wastewater
      treatment process into sparingly soluble Ag sulfides (Ag2 S). In several
      countries, sewage sludge is used as a fertilizer in agriculture. The
      bioavailability of sulfidized Ag to the terrestrial isopod Porcellio scaber was
      investigated. Sewage sludge containing transformed AgNPs was obtained from a
      laboratory-scale sewage-treatment plant operated according to Organisation for
      Economic Co-operation and Development (OECD) guideline 303a. The results of
      transmission electron microscopy with energy dispersive X-ray of sludge samples
      suggest that AgNPs were completely transformed to Ag2 S. Adult isopods were
      exposed to OECD 207 soil substrate amended with the AgNP spiked sludge for 14 d
      (uptake phase) followed by an elimination phase in unspiked soil of equal
      duration. Most of the Ag measured in P. scaber at the end of the uptake phase was
      found in the hindgut (71%), indicating that only a minor part of the estimated Ag
      content was actually assimilated by the isopods with 16.3 and 12.7% found in the
      carcass and hepatopancreas, respectively. As a result of this, the Ag content of
      the animals dropped following transition to unspiked sludge within 2 d to one
      third of the previously measured Ag concentration and remained stable at this
      level until the end of the elimination period. The present study shows that Ag2 S
      in sewage sludge is bioavailable to the terrestrial isopod P. scaber. Environ
      Toxicol Chem 2018;37:1606-1613. (c) 2018 The Authors. Environmental Toxicology
      and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.

PMID- 29363841
TI  - A Combined test using both cell sediment and supernatant cell-free DNA in pleural
      effusion shows increased sensitivity in detecting activating EGFR mutation in
      lung cancer patients.
AB  - INTRODUCTION: The aim of this study was to examine whether a combined test using
      both cell sediment and supernatant cytology cell-free DNA (ccfDNA) is more useful
      in detecting EGFR mutation than using cell sediment DNA or supernatant ccfDNA
      alone in pleural effusion of lung cancer patients. METHODS: A total of 74 lung
      adenocarcinoma patients with paired samples between primary tumour and
      corresponding metastatic tumour with both cell sediment and supernatant ccfDNA of
      pleural effusion cytology were enrolled in this study. Cell sediment and
      supernatant ccfDNA were analysed separately for EGFR mutations by polymerase
      chain reaction. RESULTS: Out of 45 patients with mutant EGFR in primary tumours,
      EGFR mutations were detected in 23 cell sediments of corresponding metastases
      (sensitivity; 51.1%) and 20 supernatant ccfDNA corresponding metastases
      (sensitivity; 44.4%). By contrast, the combined test detected EGFR mutations in
      27 corresponding metastases (sensitivity; 60.0%), and had a higher sensitivity
      than the cell sediment or the supernatant ccfDNA alone (P < .05). Out of 45
      patients with mutant EGFR, 24, three and 18 were cytologically diagnosed as
      positive, atypical or negative, respectively. The detection rate in the combined
      test was highest (95.8%) in the positive group, and mutant EGFR was also detected
      in four of 18 samples (22.2%) in the negative group. CONCLUSIONS: A combined test
      using both cell sediment DNA and supernatant ccfDNA samples increases the
      concordance rate of EGFR mutations between primary tumour and corresponding
      metastases. Our findings indicate that supernatant ccfDNA is useful even in cases
      where the cytological diagnosis is negative.

PMID- 29363842
TI  - Resident murine macrophage migration and phagocytosis are modulated by growth
      hormone.
AB  - Growth hormone (GH) plays a physiological role in the immune system. In
      macrophages, GH enhances the production of hydrogen peroxide, superoxide anions,
      nitric oxide, cytokines, and chemokines, including interferon-gamma and
      macrophage inflammatory protein-1alpha. However, some of the effects of GH
      stimulation on the biological functions of macrophages remain to be elucidated.
      Herein, we showed that in vivo GH treatment resulted in decreased expression of
      VLA-5 and VLA-6 integrins on the macrophage surface, accompanied by a reduction
      in macrophage adhesion to extracellular matrix (ECM) ligands, fibronectin, and
      laminin. Additionally, a decrease in macrophage adhesion to laminin was observed
      when the cells were treated in vitro with GH. In transwell migration assays, GH
      treated macrophages showed increased migration after 6 h. Although in vitro GH
      treatment did not influence the phagocytic activity of macrophages, when the
      treatment was performed in vivo, peritoneal macrophages from GH-treated mice
      showed a higher percentage of phagocytosis and higher phagocytic capacity than
      cells from control animals. These results led us to analyse the role of insulin
      like growth factor-1 (IGF-1), a GH stimulated factor, on macrophage phagocytosis.
      We observed an increase in phagocytic activity when J774 murine macrophages were
      treated with IGF-1 for 24 h. Our results revealed an important role for GH in
      resident macrophage migration and phagocytic activity. Specifically, we
      demonstrate that IGF-1 may be the GH stimulated factor that induces macrophage
      phagocytosis in vivo.

PMID- 29363843
TI  - What does scalp electroencephalogram coherence tell us about long-range cortical
      networks?
AB  - Long-range interactions between cortical areas are undoubtedly a key to the
      computational power of the brain. For healthy human subjects, the premier method
      for measuring brain activity on fast timescales is electroencephalography (EEG),
      and coherence between EEG signals is often used to assay functional connectivity
      between different brain regions. However, the nature of the underlying brain
      activity that is reflected in EEG coherence is currently the realm of
      speculation, because seldom have EEG signals been recorded simultaneously with
      intracranial recordings near cell bodies in multiple brain areas. Here, we take
      the early steps towards narrowing this gap in our understanding of EEG coherence
      by measuring local field potentials with microelectrode arrays in two brain areas
      (extrastriate visual area V4 and dorsolateral prefrontal cortex) simultaneously
      with EEG at the nearby scalp in rhesus macaque monkeys. Although we found inter
      area coherence at both scales of measurement, we did not find that scalp-level
      coherence was reliably related to coherence between brain areas measured
      intracranially on a trial-to-trial basis, despite that scalp-level EEG was
      related to other important features of neural oscillations, such as trial-to
      trial variability in overall amplitudes. This suggests that caution must be
      exercised when interpreting EEG coherence effects, and new theories devised about
      what aspects of neural activity long-range coherence in the EEG reflects.

PMID- 29363846
TI  - Immune responses of human dental pulp stem cells in lipopolysaccharide-induced
      microenvironment.
AB  - This study aimed to investigate the effect of inflammatory stimuli on dental pulp
      stem cells (DPSCs) by assessing their proliferation and expression of genes as
      well as proteins in lipopolysaccharide (LPS)-induced microenvironment (iDPSCs).
      DPSCs were first characterized for their mesenchymal properties prior to
      challenging them with a series of LPS concentrations from 12 to 72 h. Following
      to this, their proliferation and inflammatory based genes as well as protein
      expression were assessed. iDPSCs had demonstrated significant expression of
      mesenchymal markers. Upon exposure to LPS, the viability dropped distinctly with
      increasing concentration, as compared to control (P < 0.05). The expression of
      pro-inflammatory genes such as interleukin 6, interleukin 8 were augmented with
      exposure to LPS (P < 0.05). Similarly, cytokines like tumour necrosis factor
      (TNF) alpha and interleukin 1alpha had increased in dose dependant manner upon
      LPS exposure (P < 0.05). Our results suggest that LPS concentration between 1 and
      2 MUg/mL demonstrated inflammation induction in DPSCs that may simulate inflamed
      microenvironment of dental pulp in clinical scenario. Thus, optimizing iDPSCs
      secretome profile could be a promising approach to test various regenerative
      protocols in inflamed microenvironment.

PMID- 29363845
TI  - Non-pharmacological treatment of psychiatric disorders in individuals with
      22q11.2 deletion syndrome; a systematic review.
AB  - 22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of anxiety
      disorders, psychotic disorders, and other psychiatric conditions. In the general
      population, psychiatric disorders are treated with proven pharmacological and non
      pharmacological therapies, such as cognitive behavioral therapy (CBT). To begin
      to assess the feasibility and efficacy of non-pharmacological therapies in
      22q11.2DS, we performed a systematic search to identify literature on non
      pharmacological interventions for psychiatric disorders in individuals with
      22q11.2DS. Of 1,240 individual publications up to mid-2016 initially identified,
      11 met inclusion criteria. There were five literature reviews, five publications
      reporting original research (two originating from a single study), and one
      publication not fitting either category that suggested adaptations to an
      intervention without providing scientific evidence. None of the original research
      involved direct study of the evidence-based non-pharmacological therapies
      available for psychiatric disorders. Rather, these four studies involved computer
      based or group interventions aimed at improving neuropsychological deficits that
      may be associated with psychiatric disorders. Although the sample sizes were
      relatively small (maximum 28 participants in the intervention group), these
      reports documented the promising feasibility of these interventions, and
      improvements in domains of neuropsychological functioning, including working
      memory, attention, and social cognition. The results of this review underline the
      need for research into the feasibility and efficacy of non-pharmacological
      treatments of psychiatric disorders in individuals with 22q11.2DS to inform
      clinical care, using larger samples, and optimally, standard randomized, placebo
      controlled, clinical trials methodology.

PMID- 29363844
TI  - Neurophysiology underlying influence of stimulus reliability on audiovisual
      integration.
AB  - We tested the predictions of the dynamic reweighting model (DRM) of audiovisual
      (AV) speech integration, which posits that spectrotemporally reliable
      (informative) AV speech stimuli induce a reweighting of processing from low-level
      to high-level auditory networks. This reweighting decreases sensitivity to
      acoustic onsets and in turn increases tolerance to AV onset asynchronies (AVOA).
      EEG was recorded while subjects watched videos of a speaker uttering trisyllabic
      nonwords that varied in spectrotemporal reliability and asynchrony of the visual
      and auditory inputs. Subjects judged the stimuli as in-sync or out-of-sync.
      Results showed that subjects exhibited greater AVOA tolerance for non-blurred
      than blurred visual speech and for less than more degraded acoustic speech.
      Increased AVOA tolerance was reflected in reduced amplitude of the P1-P2 auditory
      evoked potentials, a neurophysiological indication of reduced sensitivity to
      acoustic onsets and successful AV integration. There was also sustained visual
      alpha band (8-14 Hz) suppression (desynchronization) following acoustic speech
      onsets for non-blurred vs. blurred visual speech, consistent with continuous
      engagement of the visual system as the speech unfolds. The current findings
      suggest that increased spectrotemporal reliability of acoustic and visual speech
      promotes robust AV integration, partly by suppressing sensitivity to acoustic
      onsets, in support of the DRM's reweighting mechanism. Increased visual signal
      reliability also sustains the engagement of the visual system with the auditory
      system to maintain alignment of information across modalities.

PMID- 29363847
TI  - Clinical outcomes of stapled transanal rectal resection for obstructed
      defaecation syndrome at 10-year follow-up.
AB  - AIM: The long-term efficacy of stapled transanal rectal resection (STARR) for
      surgical management of obstructed defaecation syndrome (ODS) has not been
      evaluated. Therefore, we investigated the long-term efficacy (> 10 years) of
      STARR for treatment of ODS related to rectocele or rectal intussusception and the
      factors that predict treatment outcome. METHOD: This study was a retrospective
      cohort analysis conducted on prospectively collected data. Seventy-four
      consecutive patients who underwent STARR for ODS between January 2005 and
      December 2006 in two Italian hospitals were included. RESULTS: Seventy-four
      patients [66 women; median age 61 (29-77) years] underwent STARR for ODS. No
      serious postoperative complications were recorded. Ten years postoperatively, 60
      (81%) patients completed the expected follow-up. Twenty-three patients (38%)
      reported persistent perineal pain and 13 (22%) experienced the urge to defaecate.
      ODS symptoms recurred in 24 (40%) patients after 10 years. At the 10-year follow
      up, 35% of patients were very satisfied and 28% would recommend STARR and undergo
      the same procedure again if necessary. In contrast, 21% of patients would not
      select STARR again. Previous uro-gynaecological or rectal surgery and high
      constipation scores were identified as risk factors for recurrence. CONCLUSIONS:
      Stapled transanal rectal resection significantly improves the symptoms of ODS in
      the short term. In the long term STARR is less effective, however.

PMID- 29363848
TI  - Consensus definition and essential reporting parameters of selective fetal growth
      restriction in twin pregnancy: a Delphi procedure.
AB  - OBJECTIVES: Twin pregnancies complicated by selective fetal growth restriction
      (sFGR) are associated with increased perinatal mortality and morbidity.
      Inconsistences in the diagnostic criteria for sFGR employed in existing studies
      hinder the ability to compare or combine their findings. It is therefore
      challenging to establish robust evidence-based management or monitoring pathways
      for these pregnancies. The main aim of this study was to determine, by expert
      consensus using a Delphi procedure, the key diagnostic features of and the
      essential reporting parameters in sFGR. METHODS: A Delphi process was conducted
      among an international panel of experts in sFGR in twin pregnancy. Panel members
      were provided with a list of literature-based parameters for diagnosing sFGR and
      were asked to rate their importance on a 5-point Likert scale. Parameters were
      described as solitary parameters (sufficient to diagnose sFGR, even if all other
      parameters are normal) and contributory parameters (those that require other
      abnormal parameter(s) to be present for the diagnosis of sFGR). Consensus was
      sought to determine the cut-off values for accepted parameters, as well as
      parameters used in the monitoring, management and assessment of the outcome of
      twin pregnancies complicated by sFGR. The questions were presented in two
      separate categories according to chorionicity. RESULTS: A total of 72 experts
      were approached, of whom 60 agreed to participate and entered the first round; 48
      (80%) completed all four rounds. For sFGR irrespective of chorionicity, one
      solitary parameter (estimated fetal weight (EFW) of one of the twins less than
      the third centile) was agreed. For monochorionic (MC) twin pregnancy at least two
      out of four contributory parameters (EFW less than the 10th centile of one of the
      twins, abdominal circumference (AC) of one twin less than the 10th centile, EFW
      discordance of 25% or more, and umbilical artery (UA) pulsatility index (PI) of
      the smaller twin above the 95th centile) were agreed. For sFGR in dichorionic
      (DC) twin pregnancy, at least two out of three contributory parameters (EFW of
      one twin less than the 10th centile, EFW discordance of 25% or more, and UA PI of
      the smaller twin above the 95th centile) were agreed. CONCLUSION: Consensus-based
      diagnostic features of sFGR in both MC and DC twin pregnancies, as well as cut
      off values for the parameters involved, were agreed upon by a panel of experts.
      Future studies are needed to validate these diagnostic features before they can
      be used in clinical trials of interventions.

PMID- 29363849
TI  - Impact of Th1/Th2 cytokine polarity induced by invariant NKT cells on the
      incidence of pregnancy loss in mice.
AB  - OBJECTIVE: This study aimed to investigate the association of Th1/Th2 polarity
      induced by CD1d-restricted invariant natural killer T (iNKT) cells with pregnancy
      outcome. METHODS: Two types of iNKT cell stimulants with different cytokine
      induction properties, alpha-galactosylceramide (AGC; Th1-biased inducer), and a
      sphingosine-truncated derivative of AGC (OCH; Th2-biased inducer) were
      administered to pregnant mice on day 9.5 post-coitus (pc), and the incidence of
      pregnancy loss was evaluated. Serum Th1/Th2 cytokine levels after the iNKT cell
      stimulations were assessed. Cytokine production from cultured splenocytes
      following iNKT cell activation was analyzed. RESULTS: No fetal loss was observed
      after OCH administration, in clear contrast with the high frequency of pregnancy
      loss after AGC exposure. High serum levels of IL-4 and IL-10 were detected upon
      OCH administration, whereas a temporary surge of IFN-gamma was observed after AGC
      administration. In splenocyte cultures, increases in IL-4 and IL-10 were noted
      after OCH administration, whereas IL-12 production was enhanced by AGC.
      Additionally, AGC-induced pregnancy loss was inhibited by IL-4 administration.
      CONCLUSION: The resistance of mouse pregnancy to iNKT cell stimulation by OCH and
      the prevention of AGC-induced fetal loss by IL-4 were demonstrated. In pregnancy,
      the regulation of Th1/Th2 polarity by iNKT cells is a key to healthy fetal
      growth.

PMID- 29363850
TI  - Improving image quality of mid-trimester fetal sonography in obese women: role of
      ultrasound propagation velocity.
AB  - OBJECTIVE: The quality of ultrasound images is impaired in obese patients. All
      ultrasound scanners are calibrated for an ultrasound propagation velocity of 1540
      m/s, but the propagation in fatty tissue is slower (in the order of 1450 m/s).
      The main objective of this study was to evaluate the quality of images obtained
      with different ultrasound propagation velocity settings during the mid-trimester
      fetal ultrasound examination in obese patients. METHODS: This was a cross
      sectional study using image sets of four recommended scanning planes collected
      from 32 obese pregnant women during their mid-trimester fetal scan. Each image
      set comprised three images obtained successively at three different propagation
      velocity settings (1540 m/s, 1480 m/s and 1420 m/s). A panel of 114 experts
      assessed the quality of 100 image sets, grading them from A (most acceptable) to
      C (least acceptable). Scanning-plane-specific indicators of adiposity (fatty
      layer thickness, probe-to-organ distance) were analyzed for each scanning plane.
      RESULTS: The experts had a mean of 18.1 +/- 10.2 years of experience. The grade
      distribution (A, B, C) differed significantly (P < 0.0001) between the three
      propagation velocity settings tested; at the lower speed of 1480 m/s, images were
      most often graded A, while at the conventional speed of 1540 m/s, they were most
      often graded C. Regardless of the scanning plane, the thicker the fatty layer of
      the abdominal wall in a given plane, the lower the preferred speed (P < 0.0001).
      CONCLUSION: The construction of images taking into account ultrasound propagation
      velocities lower than 1540 m/s can improve significantly the quality of images
      obtained during mid-trimester fetal ultrasonography in obese women. Copyright (c)
      2018 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29363852
TI  - The analysis of the parameters of 24-hr ECG Holter monitoring in patients with
      blood neoplasms undergoing high-dose chemotherapy and stem cell transplantation.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is a widely used
      procedure in the treatment of malignant diseases, including blood neoplasms and
      has increased survival in hematological diseases. The aim of the study was to
      analyze parameters of 24-hr ECG monitoring in patients with selected blood
      neoplasms in whom the procedure of hematopoietic stem cell transplantation was
      performed. METHODS: The study group consisted of 64 adults diagnosed with
      hematologic cancer qualified for HSCT with the previous high dose chemotherapy
      (HDC). In all patients 24-hr Holter monitoring was carried out twice. First
      examination took place prior to the HSCT procedure, and the second after
      finishing the procedure of HSCT. RESULTS: The minimal and mean heart rate (HR min
      and HR max) from 24-hr ECG recording was statistically significantly higher after
      the transplantation in comparison with the first test. The number of premature
      ventricular complexes (PVCs) was higher in the test after HSCT. In the second
      examination there was significantly higher percentage of premature ventricular
      complexes, incidents of tachycardia, and Mobitz type 1 second degree
      atrioventricular block. In regression analysis, in a group of patients with blood
      neoplasms after HSCT and HDC, administration of cyclophosphamide, fludarabine and
      total body irradiation were independent risk factors for electrocardiographic
      abnormalities in 24-hr Holter monitoring, that is, the increase in HR min, HR
      mean and PVCs. CONCLUSION: In patients with blood neoplasms undergoing HSCT more
      electrocardiographic abnormalities may be found after this procedure in
      comparison with the 24-hr Holter monitoring before transplantation.

PMID- 29363851
TI  - Wild-type p53 enhances endothelial barrier function by mediating RAC1 signalling
      and RhoA inhibition.
AB  - Inflammation is the major cause of endothelial barrier hyper-permeability,
      associated with acute lung injury and acute respiratory distress syndrome. This
      study reports that p53 "orchestrates" the defence of vascular endothelium against
      LPS, by mediating the opposing actions of Rac1 and RhoA in pulmonary tissues.
      Human lung microvascular endothelial cells treated with HSP90 inhibitors
      activated both Rac1- and P21-activated kinase, which is an essential element of
      vascular barrier function. 17AAG increased the phosphorylation of both LIMK and
      cofilin, in contrast to LPS which counteracted those effects. Mouse lung
      microvascular endothelial cells exposed to LPS exhibited decreased expression of
      phospho-cofilin. 17AAG treatment resulted in reduced levels of active cofilin.
      Silencing of cofilin pyridoxal phosphate phosphatase (PDXP) blocked the LPS
      induced hyper-permeability, and P53 inhibition reversed the 17AAG-induced PDXP
      down-regulation. P190RHOGAP suppression enhanced the LPS-triggered barrier
      dysfunction in endothelial monolayers. 17AAG treatment resulted in P190RHOGAP
      induction and blocked the LPS-induced pMLC2 up-regulation in wild-type mice.
      Pulmonary endothelial cells from "super p53" mice, which carry additional p53-tg
      alleles, exhibited a lower response to LPS than the controls. Collectively, our
      findings help elucidate the mechanisms by which p53 operates to enhance barrier
      function.

PMID- 29363853
TI  - Disruption of the methionine cycle and reduced cellular gluthathione levels
      underlie potex-potyvirus synergism in Nicotiana benthamiana.
AB  - Infection caused by the synergistic interaction of two plant viruses is typically
      manifested by severe symptoms and increased accumulation of either virus. In
      potex-potyviral synergism, the potyviral RNA silencing suppressor helper
      component proteinase (HCPro) is known to enhance the pathogenicity of the
      potexvirus counterpart. In line with this, Potato virus X (PVX; genus Potexvirus)
      genomic RNA (gRNA) accumulation and gene expression from subgenomic RNA (sgRNA)
      are increased in Nicotiana benthamiana by Potato virus A (PVA; genus Potyvirus)
      HCPro expression. Recently, we have demonstrated that PVA HCPro interferes with
      the host cell methionine cycle by interacting with its key enzymes S-adenosyl-l
      methionine synthetase (SAMS) and S-adenosyl-l-homocysteine hydrolase (SAHH). To
      study the involvement of methionine cycle enzymes in PVX infection, we knocked
      down SAMS and SAHH. Increased PVX sgRNA expression between 3 and 9 days post
      infiltration (dpi) and upregulation of (-)-strand gRNA accumulation at 9 dpi were
      observed in the SAHH-silenced background. We found that SAMS and SAHH silencing
      also caused a significant reduction in glutathione (GSH) concentration,
      specifically in PVX-infected plants between 2 and 9 dpi. Interestingly, HCPro
      expression in PVX-infected plants caused an even stronger reduction in GSH levels
      than did SAMS + SAHH silencing and a similar level of reduction was also achieved
      by knocking down GSH synthetase. PVX sgRNA expression was increased in the GSH
      synthetase-silenced background. GSH is a major antioxidant of plant cells and
      therefore GSH shortage may explain the strong oxidative stress and severe
      symptoms observed during potex-potyvirus mixed infection.

PMID- 29363854
TI  - Spatiotemporally regulated proteolysis to dissect the role of vegetative proteins
      during Bacillus subtilis sporulation: cell-specific requirement of sigmaH and
      sigmaA.
AB  - Sporulation in Bacillus subtilis is a paradigm of bacterial development, which
      involves the interaction between a larger mother cell and a smaller forespore.
      The mother cell and the forespore activate different genetic programs, leading to
      the production of sporulation-specific proteins. A critical gap in our
      understanding of sporulation is how vegetative proteins, made before sporulation
      initiation, contribute to spore formation. Here we present a system,
      spatiotemporally regulated proteolysis (STRP), which enables the rapid,
      developmentally regulated degradation of target proteins, thereby providing a
      suitable method to dissect the cell- and developmental stage-specific role of
      vegetative proteins. STRP has been used to dissect the role of two major
      vegetative sigma factors, sigmaH and sigmaA , during sporulation. The results
      suggest that sigmaH is only required in predivisional cells, where it is
      essential for sporulation initiation, but that it is dispensable during
      subsequent steps of spore formation. However, evidence has been provided that
      sigmaA plays different roles in the mother cell, where it replenishes
      housekeeping functions, and in the forespore, where it plays an unexpected role
      in promoting spore germination and outgrowth. Altogether, the results demonstrate
      that STRP has the potential to provide a comprehensive molecular dissection of
      every stage of sporulation, germination and outgrowth.

PMID- 29363855
TI  - NRP1 haploinsufficiency predisposes to the development of Tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. It
      involves anatomical abnormalities that change the normal flow of blood through
      the heart resulting in low oxygenation. Although not all of the underlying causes
      of TOF are completely understood, the disease has been associated with varying
      genetic etiologies including chromosomal abnormalities and Mendelian disorders,
      but can also occur as an isolated defect. In this report, we describe a familial
      case of TOF associated with a 1.8 Mb deletion of chromosome 10p11. Among the
      three genes in the region one is Neuropilin1 (NRP1), a membrane co-receptor of
      VEGF that modulates vasculogenesis. Hemizygous levels of NRP1 resulted in a
      reduced expression at the transcriptional and protein levels in patient-derived
      cells. Reduction of NRP1 also lead to decreased function of its activity as a co
      receptor in intermolecular VEGF signaling. These findings support that diminished
      levels of NRP1 contribute to the development of TOF, likely through its function
      in mediating VEGF signal and vasculogenesis.

PMID- 29363856
TI  - The role of nailfold capillary dropout on mortality in systemic sclerosis.
AB  - BACKGROUND: Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a
      simple technique with proven utility in the early diagnosis of systemic sclerosis
      (SSc). Its role in prognosis, however, remains uncertain. AIM: To investigate the
      possible utility of NFC in predicting survival. METHODS: Patients with SSc listed
      on the South Australian Scleroderma Register (SASR) with prior NFC performed at
      Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline
      demographic data, diagnosis, scleroderma antibody status and mortality status
      were also collected for each patient. RESULTS: The cohort consisted of 99
      patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and
      23 with an overlap scleroderma syndrome. Fifty-six patients died during the
      period of study (censured end June 2015). Patients with diffuse scleroderma had
      significantly greater capillary dropout compared with limited and overlap
      scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores
      (log-rank chi2 = 8.75, P = 0.003) and antibody status (log-rank chi2 = 13.94, P =
      0.003) were associated with mortality. ANOVA showed a significant association
      between antibody status and capillary dropout (P < 0.001). In Cox regression,
      adjustment for capillary dropout attenuated the impact of autoantibody group on
      survival. CONCLUSIONS: Nailfold capillary dropout was significantly associated
      with mortality and the severity of dropout attenuates survival dictated by
      antibody status. Together these observations support the hypothesis that
      capillary dropout is on the causal pathway between induction of scleroderma
      associated autoantibodies and mortality.

PMID- 29363857
TI  - Influence of human acute wound fluid on the antibacterial efficacy of different
      antiseptic polyurethane foam dressings: An in vitro analysis.
AB  - Treating infected acute and/or chronic wounds still represents a major challenge
      in medical care. Various interactions of antiseptic dressings with wound
      environments regarding antimicrobial efficacy remain unclear. Therefore, this
      work aimed to investigate the influence of human acute wound fluid (AWF) on the
      antimicrobial performance of different antiseptic foam dressings in vitro against
      typical bacterial wound pathogens. Eight antiseptic polyurethane foam dressings
      containing either a silver formulation or a polyhexamethylene-biguanide (PHMB)
      were assessed regarding their antimicrobial potency against Staphylococcus
      aureus, Escherichia coli, and Pseudomonas aeruginosa using a modified time-kill
      assay based on ISO EN 20743. The antiseptic efficacy was evaluated standardly as
      well as under the influence of human AWF after 2, 4, 6, and 24 hours. The
      specific chemical formulation and concentration of the antiseptic substance
      (ionic or nanocrystalline silver, silver sulfadiazine, PHMB 0.1%/0.5%) embedded
      within the dressings seemed to play a key role. For certain dressings (two
      nanocrystalline and one ionic silver dressing), the antimicrobial efficacy was
      significantly reduced under the influence of AWF compared to unchallenged test
      series. Unchallenged the efficacy of PHMB was comparable to silver against P.
      aeruginosa and even significantly superior against S. aureus and E. coli.
      Challenged with AWF the reduction rates for silver adjusted or even exceeded (P.
      aeruginosa) those of PHMB. Within a challenging wound environment, especially
      some silver formulations demonstrated a reduced bacterial reduction. Regarding
      the presented in vitro results, the biomolecular interactions of antiseptic wound
      dressings with wound fluid should be part of more extensive investigations,
      considering varying factors such as bacterial species and wound
      (micro)environment to develop targeted therapeutic regimes for the individual.

PMID- 29363858
TI  - Large-Grain Tin-Rich Perovskite Films for Efficient Solar Cells via Metal
      Alloying Technique.
AB  - Fast research progress on lead halide perovskite solar cells has been achieved in
      the past a few years. However, the presence of lead (Pb) in perovskite
      composition as a toxic element still remains a major issue for large-scale
      deployment. In this work, a novel and facile technique is presented to fabricate
      tin (Sn)-rich perovskite film using metal precursors and an alloying technique.
      Herein, the perovskite films are formed as a result of the reaction between Sn/Pb
      binary alloy metal precursors and methylammonium iodide (MAI) vapor in a chemical
      vapor deposition process carried out at 185  degrees C. It is found that in this
      approach the Pb/Sn precursors are first converted to (Pb/Sn)I2 and further
      reaction with MAI vapor leads to the formation of perovskite films. By using Pb
      Sn eutectic alloy, perovskite films with large grain sizes up to 5 um can be
      grown directly from liquid phase metal. Consequently, using an alloying technique
      and this unique growth mechanism, a less-toxic and efficient perovskite solar
      cell with a power conversion efficiency (PCE) of 14.04% is demonstrated, while
      pure Sn and Pb perovskite solar cells prepared in this manner yield PCEs of 4.62%
      and 14.21%, respectively. It is found that this alloying technique can open up a
      new direction to further explore different alloy systems (binary or ternary
      alloys) with even lower melting point.

PMID- 29363859
TI  - Modern management of T1 rectal cancer by transanal endoscopic microsurgery: a 10
      year single-centre experience.
AB  - AIM: Minimally invasive, organ-sparing surgery has been used increasingly for
      early rectal cancer in recent years. However, local recurrence remains a concern.
      This study presents a 10-year single-centre experience of recurrence after local
      excision for T1 rectal cancer. METHOD: Data were collected prospectively on all
      patients undergoing local excision by transanal endoscopic microsurgery (TEM) in
      a single institution. Data covering a 10-year period were analysed. RESULTS: In
      all, 192 patients underwent TEM for rectal cancer; 70 of these had T1 tumour in
      the TEM specimen and did not have preoperative radiotherapy. Four were managed
      with completion surgery following TEM and a further six had radiotherapy; 60
      underwent surveillance alone. Local recurrence occurred in six patients; three
      underwent salvage surgery. Estimated local recurrence at 3 years was 7.2% for the
      surveillance alone group. CONCLUSIONS: Local recurrence rates were lower than
      previous studies. Better preoperative assessment, more effective local excision
      surgery and postoperative radiotherapy may be contributory factors to a better
      than-predicted outcome. Local excision should be offered as part of standard of
      care for T1 rectal cancer in the presence of good preoperative selection and
      meticulous surveillance.

PMID- 29363860
TI  - ACE2-EPC-EXs protect ageing ECs against hypoxia/reoxygenation-induced injury
      through the miR-18a/Nox2/ROS pathway.
AB  - Oxidative stress is one of the mechanisms of ageing-associated vascular
      dysfunction. Angiotensin-converting enzyme 2 (ACE2) and microRNA (miR)-18a have
      shown to be down-regulated in ageing cells. Our previous study has shown that
      ACE2-primed endothelial progenitor cells (ACE2-EPCs) have protective effects on
      endothelial cells (ECs), which might be due to their released exosomes (EXs).
      Here, we aimed to investigate whether ACE2-EPC-EXs could attenuate
      hypoxia/reoxygenation (H/R)-induced injury in ageing ECs through their carried
      miR-18a. Young and angiotensin II-induced ageing ECs were subjected to H/R and co
      cultured with vehicle (medium), EPC-EXs, ACE2-EPCs-EXs, ACE2-EPCs-EXs + DX600 or
      ACE2-EPCs-EXs with miR-18a deficiency (ACE2-EPCs-EXsanti-miR-18a ). Results
      showed (1) ageing ECs displayed increased senescence, apoptosis and ROS
      production, but decreased ACE2 and miR-18a expressions and tube formation
      ability; (2) under H/R condition, ageing ECs showed higher rate of apoptosis, ROS
      overproduction and nitric oxide reduction, up-regulation of Nox2, down-regulation
      of ACE2, miR-18a and eNOS, and compromised tube formation ability; (3) compared
      with EPC-EXs, ACE2-EPC-EXs had better efficiencies on protecting ECs from H/R
      induced changes; (4) The protective effects were less seen in ACE2-EPCs-EXs +
      DX600 and ACE2-EPCs-EXsanti-miR-18a groups. These data suggest that ACE-EPCs-EXs
      have better protective effects on H/R injury in ageing ECs which could be through
      their carried miR-18a and subsequently down-regulating the Nox2/ROS pathway.

PMID- 29363861
TI  - Positive autoregulation and repression of transactivation are key regulatory
      features of the Candida glabrata Pdr1 transcription factor.
AB  - Resistance to azole drugs, the major clinical antifungal compounds, is most
      commonly due to gain-of-function (GOF) substitution mutations in a gene called
      PDR1 in the fungal pathogen Candida glabrata. PDR1 encodes a zinc cluster
      containing transcription factor. GOF forms of Pdr1 drive high level expression of
      downstream target gene expression with accompanying azole resistance. PDR1 has
      two homologous genes in Saccharomyces cerevisiae, called ScPDR1 and ScPDR3. This
      study provides evidence that the PDR1 gene in C. glabrata represents a blend of
      the properties found in the two S. cerevisiae genes. We demonstrated that GOF
      Pdr1 derivatives are overproduced at the protein level and less stable than the
      wild-type protein. Overproduction of wild-type Pdr1 increased target gene
      expression but to a lesser extent than GOF derivatives. Site-directed mutagenesis
      of Pdr1 binding sites in the PDR1 promoter provided clear demonstration that
      autoregulation of PDR1 is required for its normal function. An internal deletion
      mutant of Pdr1 lacking its central regulatory domain behaved as a hyperactive
      transcription factor that was lethal unless conditionally expressed. A full
      understanding of the regulation of Pdr1 will provide a new avenue of interfering
      with azole resistance in C. glabrata.

PMID- 29363862
TI  - miR-15b-5p facilitates the tumorigenicity by targeting RECK and predicts tumour
      recurrence in prostate cancer.
AB  - MicroRNAs (miRNAs) have been reported to participate in many biological
      behaviours of multiple malignancies. Recent studies have shown that miR-15b-5p
      (miR-15b) exhibits dual roles by accelerating or blocking tumour progression.
      However, the molecular mechanisms by which miR-15b contributes to prostate cancer
      (PCa) are still elusive. Here, miR-15b expression was found significantly up
      regulated in PCa in comparison with the normal samples and was positively
      correlated with age and Gleason score in patients with PCa. Notably, PCa patients
      with miR-15b high expression displayed a higher recurrence rate than those with
      miR-15b low expression (P = 0.0058). Knockdown of miR-15b suppressed cell growth
      and invasiveness in 22RV1 and PC3 cells, while overexpression of miR-15b reversed
      these effects. Then, we validated that RECK acted as a direct target of miR-15b
      by dual-luciferase assay and revealed the negative correlation of RECK with miR
      15b expression in PCa tissues. Ectopic expression of RECK reduced cell
      proliferation and invasive potential and partially abrogated the tumour-promoting
      effects caused by miR-15b overexpression. Additionally, miR-15b knockdown
      inhibited tumour growth activity in a mouse PCa xenograft model. Taken together,
      our findings indicate that miR-15b promotes the progression of PCa cells by
      targeting RECK and represents a potential marker for patients with PCa.

PMID- 29363863
TI  - Acute hypocalcaemia following denosumab in heart and lung transplant patients
      with osteoporosis.
AB  - BACKGROUND: Osteoporosis is highly prevalent in the heart and lung transplant
      population. Given high rates of concurrent renal impairment, there is increasing
      use of denosumab in this population. However, denosumab may be associated with
      hypocalcaemia, particularly in patients with chronic kidney disease (CKD). AIM:
      To explore the risk of hypocalcaemia in a heart and lung transplant cohort
      prescribed denosumab for osteoporosis. METHODS: We performed a retrospective
      database review of all surviving heart and lung transplant patients who had
      received denosumab for osteoporosis between January 2012 and November 2015. We
      assessed the rates of hypocalcaemia in this cohort and collected baseline
      clinical data to determine associated factors. RESULTS: Ten patients received
      denosumab and had laboratory results available within 3 months of the dose. Of
      these, three patients developed severe (grade 4) hypocalcaemia, while two
      patients developed mild (grade 1) hypocalcaemia. In comparison to the five
      patients who remained normocalcaemic, patients with hypocalcaemia had
      significantly lower baseline mean estimated glomerular filtration rate but
      similar baseline mean corrected serum calcium. Unexpectedly, patients developing
      hypocalcaemia had non-significantly higher levels of 25-hydroxyvitamin D and
      lower baseline doses of prednisone. CONCLUSIONS: In heart and lung transplant
      patients, denosumab should be used judiciously in patients with advanced renal
      disease due to the risk of hypocalcaemia.

PMID- 29363864
TI  - SRR intronic variation inhibits expression of its neighbouring SMG6 gene and
      protects against temporal lobe epilepsy.
AB  - D-serine is a predominant N-methyl-D-aspartate receptor co-agonist with
      glutamate, and excessive activation of the receptor plays a substantial role in
      epileptic seizures. Serine racemase (SRR) is responsible for transforming L
      serine to D-serine. In this study, we aimed to investigate the genetic roles of
      SRR and a neighbouring gene, nonsense-mediated mRNA decay factor (SMG6), in
      temporal lobe epilepsy (TLE). Here, a total of 496 TLE patients and 528 healthy
      individuals were successfully genotyped for three SRR tag single nucleotide
      polymorphisms. The frequencies of the GG genotype at rs4523957 T > G were reduced
      in the TLE cases in the initial cohort (cohort 1) and were confirmed in the
      independent cohort (cohort 2). An analysis of all TLE cases in cohort 1 + 2
      revealed that the seizure frequency and drug-resistant incidence were
      significantly decreased in carriers of the GG genotype at rs4523957.
      Intriguingly, the activity of the SMG6 promoter with the mutant allele at
      rs4523957 decreased by 22% in the dual-luciferase assay, and up-regulated
      expression of SMG6 was observed in an epilepsy rat model. This study provides the
      first demonstration that the GG genotype is a protective marker against TLE. In
      particular, variation at rs4523957 likely inhibits SMG6 transcription and plays a
      key role against susceptibility to and severity of TLE. The significance of SMG6
      hyperfunction in epileptic seizures deserves to be investigated in future
      studies.

PMID- 29363870
TI  - A putative LysR-type transcriptional regulator PrhO positively regulates the type
      III secretion system and contributes to the virulence of Ralstonia solanacearum.
AB  - LysR-type transcriptional regulators (LTTRs) are ubiquitous and abundant amongst
      bacteria and control a variety of cellular processes. Here, we investigated the
      effect of Rsc1880 (a putative LTTR, hereafter designated as PrhO) on the
      pathogenicity of Ralstonia solanacearum. Deletion of prhO substantially reduced
      the expression of the type III secretion system (T3SS) both in vitro and in
      planta, and resulted in significantly impaired virulence in tomato and tobacco
      plants. Complementary prhO completely restored the reduced virulence and T3SS
      expression to that of the wild-type. Moreover, PrhO-dependent T3SS and virulence
      were conserved amongst R. solanacearum species. However, deletion of prhO did not
      alter biofilm formation, swimming mobility and in planta growth. The expression
      of some type III effectors was significantly reduced in prhO mutants, but the
      hypersensitive response was not affected in tobacco leaves. Consistent with the
      key regulatory role of HrpB on T3SS, PrhO positively regulated the T3SS through
      HrpB. Furthermore, PrhO regulated hrpB expression via two close paralogues, HrpG
      and PrhG, which are two-component response regulators and positively regulate
      hrpB expression in a parallel manner. However, deletion of prhO did not alter the
      expression of phcA, prhJ and prhN, which are also involved in hrpB regulation. In
      addition, PrhO was expressed in a cell density-dependent manner, but negatively
      repressed by itself. No regulation was observed for HrpB, PhcA and PrhN on prhO
      expression. Taken together, we genetically demonstrated that PrhO is a novel
      virulence regulator of R. solanacearum, which positively regulates T3SS
      expression through HrpG, PrhG and HrpB and contributes to virulence.

PMID- 29363872
TI  - Evolutionary analyses of the avirulence effector AvrStb6 in global populations of
      Zymoseptoria tritici identify candidate amino acids involved in recognition.
AB  - We analysed the population genetic diversity of AvrStb6, the first avirulence
      gene cloned from the wheat pathogen Zymoseptoria tritici, using 142 Z. tritici
      strains sampled from four wheat fields growing on three continents. Although
      AvrStb6 was located in a recombination hotspot, it was found in every strain,
      with 71 polymorphic sites that produced 41 distinct DNA haplotypes encoding 30
      AvrStb6 protein isoforms. An AvrStb6 homologue was found in the closest known
      relative, Z. pseudotritici, but not in three other closely related Zymoseptoria
      species, indicating that this gene has emerged in Zymoseptoria quite recently.
      Two AvrStb6 homologues with nucleotide similarities greater than 70% were
      identified on chromosome 10 in all Z. tritici isolates, suggesting that AvrStb6
      belongs to a multigene family of candidate effectors that has expanded recently
      through gene duplication. The AvrStb6 sequences exhibited strong evidence for non
      neutral evolution, including a large number of non-synonymous mutations, with
      significant positive diversifying selection operating on nine of the 82 codons.
      It appears that balancing selection is operating across the entire gene in
      natural field populations. There was also evidence for co-evolving codons within
      the gene that may reflect compensatory mutations associated with the evasion of
      recognition by Stb6. Intragenic recombination also appears to have affected the
      diversity of AvrStb6.

PMID- 29363871
TI  - Effects of d-galactose-induced ageing on the heart and its potential
      interventions.
AB  - Ageing is a strong independent risk factor for disability, morbidity and
      mortality. Post-mitotic cells including those in the heart are a particular risk
      to age-related deterioration. As the occurrence of heart disease is increasing
      rapidly with an ageing population, knowledge regarding the mechanisms of age
      related cardiac susceptibility and possible therapeutic interventions needs to be
      acquired to prevent advancing levels of heart disease. To understand more about
      the ageing heart, numerous aged animal models are being used to explore the
      underlying mechanisms. Due to time-consuming for investigations involving
      naturally aged animals, mimetic ageing models are being utilized to assess the
      related effects of ageing on disease occurrence. d-galactose is one of the
      substances used to instigate ageing in various models, and techniques involving
      this have been widely used since 1991. However, the mechanism through which d
      galactose induces ageing in the heart remains unclear. The aim of this review was
      to comprehensively summarize the current findings from in vitro and in vivo
      studies on the effects of d-galactose-induced ageing on the heart, and possible
      therapeutic interventions against ageing heart models. From this review, we hope
      to provide invaluable information for future studies and based on the findings
      from experiments involving animals, we can inform possible therapeutic strategies
      for the prevention of age-related heart diseases in clinical settings.

PMID- 29363873
TI  - The Long-Term Durability of Multilumen Concentric Percutaneous Spinal Cord
      Stimulator Leads.
AB  - BACKGROUND: Lead fracture is a well-known complication of cylindrical spinal cord
      stimulator leads. In order to reduce this complication, anchor design and
      techniques have been modified, but internal lead design has received little
      attention. OBJECTIVES: The goal of this study was to study the impact of lead
      design by a retrospective determination of the fracture rate of multilumen
      concentric (MLC) 8-contact leads. STUDY DESIGN: Retrospective chart review.
      SETTING: University teaching hospital. METHODS: A registry of spinal cord
      stimulator implants and corresponding billing data were used to identify
      patients. Procedural details were reviewed for technique, lead insertion,
      anchoring details, manufacturer, and lead longevity from 2002 to 2014. Data
      storage was in RedCap data-capturing software (REDCap eData Collection web-based
      application). All analyses were performed using SAS 9.3 (SAS Institute, Cary, NC,
      U.S.A.). RESULTS: In a near 12"-year time period, 172 patients received 305
      permanently implanted 8-contact leads, with an overall fracture rate of 4.3%. Of
      these, 191 leads were of the MLC design. No lead fracture was observed in the MLC
      leads over an average 4.5 years of follow-up. LIMITATION: Retrospective single
      center. CONCLUSION: MLC lead design has the potential to significantly mitigate
      lead fracture.

PMID- 29363874
TI  - Ultrathin Nitrogen-Doped Carbon Layer Uniformly Supported on Graphene Frameworks
      as Ultrahigh-Capacity Anode for Lithium-Ion Full Battery.
AB  - The designable structure with 3D structure, ultrathin 2D nanosheets, and
      heteroatom doping are considered as highly promising routes to improve the
      electrochemical performance of carbon materials as anodes for lithium-ion
      batteries. However, it remains a significant challenge to efficiently integrate
      3D interconnected porous frameworks with 2D tunable heteroatom-doped ultrathin
      carbon layers to further boost the performance. Herein, a novel nanostructure
      consisting of a uniform ultrathin N-doped carbon layer in situ coated on a 3D
      graphene framework (NC@GF) through solvothermal self-assembly/polymerization and
      pyrolysis is reported. The NC@GF with the nanosheets thickness of 4.0 nm and N
      content of 4.13 at% exhibits an ultrahigh reversible capacity of 2018 mA h g-1 at
      0.5 A g-1 and an ultrafast charge-discharge feature with a remarkable capacity of
      340 mA h g-1 at an ultrahigh current density of 40 A g-1 and a superlong cycle
      life with a capacity retention of 93% after 10 000 cycles at 40 A g-1 . More
      importantly, when coupled with LiFePO4 cathode, the fabricated lithium-ion full
      cells also exhibit high capacity and excellent rate and cycling performances,
      highlighting the practicability of this NC@GF.

PMID- 29363875
TI  - The evolving mystery of why skeletal muscle is spared in seropositive
      neuromyelitis optica.

PMID- 29363877
TI  - Improving outcomes in recurrent and other new foot ulcers after healed plantar
      forefoot diabetic ulcer.

PMID- 29363876
TI  - Zotepine-induced convulsion at a low dose in a case of paranoid schizophrenia.

PMID- 29363878
TI  - Genetic polymorphisms of GPR126 are functionally associated with PUMC
      classifications of adolescent idiopathic scoliosis in a Northern Han population.
AB  - GPR126 has been identified to be associated with AIS (Adolescent Idiopathic
      Scoliosis) in different populations, but data on the northern Chinese population
      are unavailable. Additionally, it is important to know the exact clinical
      phenotypes associated with specific genetic polymorphisms. Fourteen SNP (single
      nucleotide polymorphism) loci in GPR126 were genotyped in 480 northern Chinese
      Han AIS patients and 841 controls. These patients were classified into three
      types based on the PUMC classification system. Luciferase assays were used to
      investigate their regulation of GPR126 transcription activity. Combined and
      stratified genotype-phenotype association analyses were conducted. The alleles
      rs225694, rs7774095 and rs2294773 were significantly associated with AIS (P =
      0.021, 0.048 and 0.023, respectively). rs225694 and rs7774095 potentially have
      regulatory functions for the GRP126 gene. Correlation analysis revealed that
      allele A of rs225694 was a risk allele only for PUMC type II AIS (P = 0.036) and
      allele G of rs2294773 was a risk allele only for PUMC type I AIS (P = 0.018). In
      summary, rs225694, rs7774095 and rs2294773 are significantly associated with
      disease in northern Chinese Han AIS patients. The SNPs rs225694 and rs2294773 are
      associated with different AIS PUMC classifications.

PMID- 29363879
TI  - Co-expression of NF-kappaB-p65 and phosphorylated NF-kappaB-p105 is associated
      with poor prognosis in surgically resectable non-small cell lung cancer.
AB  - Nuclear factor-kappa B (NF-kappaB) as a prognostic marker remains unclear in non
      small cell lung cancer (NSCLC). Here, we studied NF-kappaB-p65 (p65) expression
      and phosphorylated NF-kappaB-p105 (p-p105) expression in NSCLC and correlated the
      finding with overall survival (OS) and clinicopathological features. A total of
      186 archival samples from patients with surgically resectable NSCLC were probed
      with p65 and p-p105 (Ser 932). The p65-positive expression and p-p105-positive
      expression were defined as distinct nuclear p65 and cytoplasmic p-p105 labelling
      in at least 1% of tumour cells, respectively. The positive staining of p65 alone,
      p-p105 alone and co-expression of p65 and p-p105 were observed in 61 (32.8%), 90
      (48.4%) and 35 (18.8%) patients, respectively. Co-expression of p65 and p-p105
      but not of either p65 or p-p105 alone was associated with a poor prognosis.
      Patients with co-expression of p65 and p-p105 had a shorter OS than others,
      median OS 26.5 months versus 64.1 months, HR 1.85 (95% CI: 1.18-2.91), P = 0.007.
      There was no statistically significant association between clinicopathological
      characteristics and either p65 or p-p105 alone or co-expression of p65 and p
      p105. This indicates that co-expression of p65 and p-p105 was a poor prognostic
      factor, and pathologic studies of NF-kappaB expression could include multiple
      pathway components in NSCLC.

PMID- 29363880
TI  - Habit-tic cough: Presentation and outcome with simple reassurance.
AB  - OBJECTIVES: Our therapeutic approach to a habit/tic cough is simple reassurance
      in a single consultation. To quality assure our practice, we followed up children
      to determine outcomes at least 3 months after diagnosis. DESIGN: Consecutive
      children diagnosed over 6 years were studied. Medical records were analyzed
      retrospectively and parents answered a scripted verbal survey. RESULTS: Fifty
      five patients were diagnosed (median age 9.9 years), with a median cough duration
      of 3 months (IQR 2-7.5 months, range up to 3 years). In 51/55 (93%) cases, cough
      was absent during sleep. 51/55 (93%) received prior medications with median 3
      therapeutic trials, none of which resolved the cough. Follow-up was possible in
      39/55 (71%) children after a median duration of 1.9 years. In 32/39 (82%), the
      cough had resolved completely (59% within 4 weeks, including 12% on the day), and
      it improved in 6/39 (15%). In the 26/39 (67%) parents who said they believed the
      diagnosis, there was 96% resolution of the cough, versus the 13/39 (33%) who were
      sceptical or disbelieving, when there was only 54% resolution. 7/39 (18%)
      children were later diagnosed with a tic disorder, functional symptoms, or a
      behavioural/psychiatric disorder. CONCLUSIONS: Habit cough can be diagnosed from
      the characteristic history; the crucial question is whether the cough disappears
      during sleep. We have shown successful long term outcomes following a single
      consultation with simple reassurance, but it is important that the child and
      parents believe the explanation. It is not uncommon for subsequent tic disorders
      or behavioral issues to emerge.

PMID- 29363881
TI  - Exploration of differentially expressed plasma proteins in patients with lung
      adenocarcinoma using iTRAQ-coupled 2D LC-MS/MS.
AB  - BACKGROUND: Lung adenocarcinoma is characterized by early asymptomatic
      progression and metastasis. Appearance of respiratory symptoms usually means the
      disease is aggravated. The aim of this study was to identify the protein profile
      in plasma of lung adenocarcinoma of stages I-IV, and look for novel diagnostic
      biomarkers. METHODS: Isobaric tags for relative and absolute quantification
      (iTRAQ) coupled with two dimensional liquid chromatography - tandem mass
      spectrometry technology (2D LC-MS/MS) was applied to separate and identify
      differential expression of proteins in plasma specimens from 10 healthy
      individuals, 10 patients with pneumonia, 7 patients with lung adenocarcinoma of
      stages I-II, respectively, and 10 patients with lung adenocarcinoma of stages III
      IV, then analyze the functions of the differential expression of proteins by
      bioinformatics. RESULTS: ADAMTS-like protein 4, Fibrinogen-like protein 1
      precursor, secretoglobin family 3A member 2 and haptoglobin were up-regulated in
      patients with lung adenocarcinoma by proteomics analysis, and the expression
      levels of SCGB3A2 and Hp by ELISA were consistent. Pathway analysis of identified
      differential expression of proteins showed they were mainly involved in
      chemokine/p53/TGF-beta signaling pathway. CONCLUSIONS: Plasma SCGB3A2 is a
      potential maker for diagnosis of primary pulmonary adenocarcinoma. Abnormal post
      translational protein modification may be associated with the progression of lung
      cancer.

PMID- 29363882
TI  - Baseline fragmented QRS increases the risk of major arrhythmic events in
      hypertrophic cardiomyopathy: Systematic review and meta-analysis.
AB  - BACKGROUND: Fragmented QRS reflects disturbances in the myocardium predisposing
      the heart to ventricular tachyarrhythmias. Recent studies suggest that fragmented
      QRS (fQRS) is associated with worse major arrhythmic events in hypertrophic
      cardiomyopathy (HCM). However, a systematic review and meta-analysis of the
      literature has not been done. We assessed the association between fQRS and major
      arrhythmic events in hypertrophic cardiomyopathy by a systematic review of the
      literature and a meta-analysis. METHODS: We comprehensively searched the
      databases of MEDLINE and EMBASE from inception to May 2017. Included studies were
      published prospective or retrospective cohort studies that compared major
      arrhythmic events (sustained ventricular tachycardia, sudden cardiac arrest, or
      sudden cardiac death) in HCM with fQRS versus non-fQRS. Data from each study were
      combined using the random-effects, generic inverse variance method of DerSimonian
      and Laird to calculate risk ratios and 95% confidence intervals. RESULTS: Five
      studies from January 2013 to May 2017 were included in this meta-analysis
      involving 673 subjects with HCM (205 fQRS and 468 non-fQRS). Fragmented QRS was
      associated with major arrhythmic events (pooled risk ratio = 7.29, 95% confidence
      interval: 4.00-13.29, p < .01, I2  = 0%). CONCLUSION: Baseline fQRS increased
      major arrhythmic events up to sevenfold. Our study suggests that fQRS could be an
      important tool for risk assessment in patients with HCM.

PMID- 29363883
TI  - Older people's perceptions of the quality of oral care in short-term care units:
      A cross-sectional study.
AB  - BACKGROUND: There is a lack of knowledge about oral care among older people
      living in short-term care (STC) units and how the quality of oral care provided
      by nursing staff is perceived by the older people. AIM: To (i) describe person
      related conditions among older people in STC, (ii) describe and compare
      perceptions of the quality of oral care (including perceptions of care received
      and the subjective importance of such care), within and between older people who
      have the ability to perform oral self-care and those who are dependent on help
      with oral care and (iii) examine the relationship between person-related
      conditions and the quality of oral care. METHODS: A cross-sectional study was
      conducted with 391 older people in STC units in Sweden based on self-reported
      questionnaire and clinical assessments. RESULTS: The older people were assessed
      as having normal oral health (2%), moderate oral health problems (78%) or severe
      oral health problems (20%). When comparing older people's perceptions of quality
      of oral care in terms of perceived reality and subjective importance, significant
      differences appeared within and between groups. Psychological well-being had a
      significant relationship with perception of the quality of oral care (both
      perceived reality and subjective importance), and gender and oral health status
      had a significant relationship with subjective importance. CONCLUSIONS: Older
      people's perceptions of areas for improvement regarding quality of oral care is a
      new and important knowledge for nursing staff in STC units. Older people want
      personalised information regarding oral health and oral care. Registered Nurses
      who take the responsibility in nursing care for older people's oral health may
      avoid unnecessary suffering by older people caused by oral health problems.
      IMPLICATIONS FOR PRACTICE: Older people's perspective is an important component
      for quality work and might lead to improvements in the quality of oral care in
      STC.

PMID- 29363884
TI  - A widely conserved bacterial cytoskeletal component influences unique helical
      shape and motility of the spirochete Leptospira biflexa.
AB  - Leptospires and other members of the evolutionarily ancient phylum of
      Spirochaetes are bacteria often characterized by long, highly motile spiral- or
      wave-shaped cells. Morphology and motility are critical factors in spirochete
      physiology, contributing to the ability of these bacteria to successfully
      colonize diverse environments. However, the mechanisms conferring the helical
      structure of Leptospira spp. have yet to be fully elucidated. We have identified
      five Leptospira biflexa bactofilin proteins, a recently characterized protein
      family with cytoskeletal properties. These five bactofilins are conserved in all
      species of the Leptospiraceae, indicating that these proteins arose early in the
      evolution of this family. One member of this protein family, LbbD, confers the
      optimal pitch distance in the helical structure of L. biflexa. Mutants lacking
      lbbD display a unique compressed helical morphology, a reduced motility and a
      decreased ability to tolerate cell wall stressors. The change in the helical
      spacing, combined with the motility and cell wall integrity defects, showcases
      the intimate relationship and coevolution between shape and motility in these
      spirochetes.

PMID- 29363885
TI  - Baby-friendly hospital practices are associated with duration of full
      breastfeeding in primiparous but not multiparous Iranian women.
AB  - There is evidence that the Baby-Friendly Hospital Initiative (BFHI) results in
      improved breastfeeding outcomes in Western countries, but little is known of its
      impact in Middle-Eastern countries. This study investigated the impact of BFHI
      practices on duration of full breastfeeding in a cohort of 700 Iranian mothers
      recruited between June 2014 and March 2015 from maternity hospitals in Shiraz and
      followed-up prospectively for 6 months. At baseline, mothers self-reported
      exposure to 7 of the BFHI Ten Steps to Successful Breastfeeding (Steps 3 to 9).
      Data on breastfeeding outcomes were collected at baseline, 1, 3, 4, and 6 months
      postpartum. Cox regression analysis was conducted to determine the impact of
      individual and cumulative BFHI Steps on the duration of full breastfeeding,
      defined as the number of weeks since discharge that an infant received only
      breast milk and no complementary formula or food. Mothers reported experiencing
      on average 3.9 (SD 1.13, range 1 to 7) Steps, and only 28% of infants were fully
      breastfed at 6 months. There was a protective inverse relationship for
      primiparous (p for trend = .022) but not multiparous mothers (p for trend =
      .069), between the number of Steps a woman was exposed to and the likelihood of
      her discontinuing full breastfeeding within 6 months postpartum. Greater exposure
      to BFHI practices potentially could increase primiparous mothers' chances of
      fully breastfeeding to 6 months. Continual monitoring of the BFHI Steps and
      repeated education of healthcare staff are required to ensure that Iranian
      mothers receive adequate breastfeeding support.

PMID- 29363888
TI  - Decision-making in a bisexual line and a thelytokous Wolbachia-infected line of
      Trichogramma dendrolimi Matsumura (Hymenoptera: Trichogrammatidae) regarding
      behavior toward their hosts.
AB  - BACKGROUND: The use of thelytokous Wolbachia-infected Trichogramma (parasitic
      wasps) has long been considered as a way to enhance the efficacy of biocontrol.
      However, Wolbachia can affect the host physiology. We compared decision-making
      between bisexual and thelytokous Wolbachia-infected lines of Trichogramma
      dendrolimi Matsumura regarding behavior toward fresh and old eggs of Corcyra
      cephalonica at 25 +/- 1  degrees C and 70 +/- 5% relative humidity. RESULTS: The
      behavioral patterns and sequences of the two lines were basically the same. The
      durations of various behavioral patterns and values of fitness indicators of the
      bisexual line on fresh eggs were generally significantly shorter and better,
      respectively, than on old eggs, whereas the thelytokous line behaved similarly
      toward the two types of eggs, and differences in most fitness indicators between
      fresh and old eggs were not significant. On fresh eggs, the durations of various
      behaviors in the bisexual line were generally significantly shorter than in the
      thelytokous line and the fitness indicators were generally significantly better.
      CONCLUSION: Wolbachia affected the fitness of T. dendrolimi negatively. The
      potential of the thelytokous line as a biocontrol agent would not be as good as
      that of the bisexual line when decision-making only is considered. Therefore,
      further evaluations need to be carried out before the thelytokous line can be
      used in practical biocontrol. (c) 2018 Society of Chemical Industry.

PMID- 29363886
TI  - Honokiol inhibits in vitro and in vivo growth of oral squamous cell carcinoma
      through induction of apoptosis, cell cycle arrest and autophagy.
AB  - Honokiol, an active natural product derived from Magnolia officinalis, exerted
      anticancer effects through a variety of mechanisms on multiple types of cancers.
      In this study, the molecular mechanisms of honokiol in suppressing the human oral
      squamous cell carcinoma (OSCC) cells were evaluated. Treatment of two OSCC cell
      lines with honokiol resulted in reducing the cell proliferation and arresting the
      cell cycle at G1 stage which was correlated with the down-regulation of Cdk2 and
      Cdk4 and the up-regulation of cell cycle suppressors, p21 and p27. In addition,
      the caspase-dependent programmed cell death was substantially detected, and the
      autophagy was induced as the autophagosome formation and autophagic flux
      proceeded. Modulation of autophagy by autophagic inducer, rapamycin or
      inhibitors, 3-MA or bafilomycin, potentiated the honokiol-mediated anti-OSCC
      effects where honokiol exerted multiple actions in suppression of MAPK pathway
      and regulation of Akt/mTOR or AMPK pathways. As compared to clinical therapeutic
      agent, 5-FU, honokiol exhibited more potent activity against OSCC cells and
      synergistically enhanced the cytotoxic effect of 5-FU. Furthermore, orally
      administrated honokiol exerted effective antitumour activity in vivo in OSCC
      xenografted mice. Thus, this study revealed that honokiol could be a promising
      candidate in preventing human OSCCs.

PMID- 29363887
TI  - Genome-wide identification of urinary cell-free microRNAs for non-invasive
      detection of bladder cancer.
AB  - Urinary microRNAs (miRNAs) are emerging as clinically useful tool for early and
      non-invasive detection of various types of cancer including bladder cancer (BCA).
      In this study, 205 patients with BCA and 99 healthy controls were prospectively
      enrolled. Expression profiles of urinary miRNAs were obtained using Affymetrix
      miRNA microarrays (2578 miRNAs) and candidate miRNAs further validated in
      independent cohorts using qRT-PCR. Whole-genome profiling identified 76 miRNAs
      with significantly different concentrations in urine of BCA compared to controls
      (P < 0.01). In the training and independent validation phase of the study, miR-31
      5p, miR-93-5p and miR-191-5p were confirmed to have significantly higher levels
      in urine of patients with BCA in comparison with controls (P < 0.01). We further
      established 2-miRNA-based urinary DxScore (miR-93-5p, miR-31-5p) enabling
      sensitive BCA detection with AUC being 0.84 and 0.81 in the training and
      validation phase, respectively. Moreover, DxScore significantly differed in the
      various histopathological subgroups of BCA and decreased post-operatively. In
      conclusion, we identified and independently validated cell-free urinary miRNAs as
      promising biomarkers enabling non-invasive detection of BCA.

PMID- 29363889
TI  - How to undertake a nutritional assessment in adults.
AB  - RATIONALE AND KEY POINTS: Nutritional assessment in adults should begin on first
      contact with the patient, and is an ongoing process that can take place over
      several hours or days. A comprehensive nutritional assessment involves the nurse
      examining the patient's physical and psychological state, as well as considering
      any social issues that may affect their nutrition. REFLECTIVE ACTIVITY: 'How to'
      articles can help update your practice and ensure it remains evidence-based.
      Apply this article to your practice. Reflect on and write a short account of.

PMID- 29363890
TI  - Implementation of e-portfolios for the professional development of Admiral
      Nurses.
AB  - Nurses are required to maintain their fitness to practise through continuing
      professional development activities, and must demonstrate this by maintaining a
      portfolio of evidence that should be available for inspection every three years.
      The Nursing and Midwifery Council introduced revalidation in 2016 to demonstrate
      that nurses are practising safely and effectively. Nurses, however, are busy
      healthcare professionals and, as well as clinical practice, they have other
      demands on their time, such as providing evidence for annual appraisals. Admiral
      Nurses, specialist dementia nurses who support families living with dementia,
      also have a three-tier competency framework designed to demonstrate their
      acquired expertise and knowledge in dementia care. To support Admiral Nurses in
      managing these activities, the charity Dementia UK gave them access to the
      PebblePad e-portfolio system. This article details the implementation and
      outcomes of this project.

PMID- 29363891
TI  - Symptom management in women undergoing the menopause.
AB  - The menopause is a physiological event involving ovarian failure as a result of a
      loss of ovarian follicular activity, which leads to oestrogen deficiency,
      resulting in permanent cessation of menstruation and loss of reproductive
      function. Women undergoing the menopause are seen in a range of healthcare
      settings. It is important that all nurses, particularly those practising in
      primary care and women's health, have an understanding of the symptoms, treatment
      and long-term implications of the menopause on women's health and quality of
      life. This article outlines the symptoms of the menopause and the available
      treatments for these, including hormone replacement therapy, non-hormonal
      treatments and alternative therapies, and discusses how nurses can assist women
      undergoing the menopause to improve their health and quality of life during this
      often challenging time.

PMID- 29363892
TI  - A modified activity protocol for claudication.
AB  - BACKGROUND: We propose the use of a monitored step tracking device, the FitBit(r)
      to supplant supervised exercise therapy (SET) programs to facilitate improvement
      in walking distance in Veteran claudicators. METHODS: In this prospective study,
      we enrolled fortynine patients with clinical evidence of lower extremity
      claudication in a six month walking program. Each patient was given a FitBit(r)
      device to track daily number of steps. Patients were seen in clinic monthly to
      collect data and discuss walking goals. Surveys at the beginning and end of each
      study assessed patient perception of changes in walking distance as well as
      symptoms. The primary outcome was monthly distance walked. Changes over time in
      each outcome variables were examined using a random effects mixed model. RESULTS:
      In the first month, the adjusted mean number of steps per day was 3492 (95% CI
      2661 4322). By month 5, this had increased to 4502 (36365367) (p=.0007). 28
      patients used the tracker at least for 1 month, while 21 (43%) did not. Being
      bothered by symptoms was the only patient variable that was significantly
      associated with use of the FitBit(r). Those who used the tracker tended to be
      younger, heavier, more active, and were more likely to have diabetes.
      CONCLUSIONS: In the Veteran population, the use of a monitored step tracking
      device such as the FitBit(r) is a potentially effective strategy to improve
      walking distance in claudicators particularly in those with mild symptoms.
      Additional investigation is needed to determine which patients will benefit most
      from this walking protocol.

PMID- 29363893
TI  - Is management of complex abdominal aortic aneurysms consistent? A questionnaire
      based survey.
AB  - BACKGROUND: Complex abdominal aortic aneurysm (AAA) is a relatively common
      presentation to the vascular specialist. Despite this there is little consensus
      on how to manage the often co-morbid group of patients. Recent advances in
      endovascular technology have led to the availability of multiple devices, many of
      which could be used to treat the same aneurysm. The aim of this study was to
      quantify this potential variability across vascular specialists from multiple
      countries. METHODS: An online survey was emailed to members of the Vascular
      Society for Great Britain and Ireland (VSGBI), the Canadian Society for Vascular
      Surgery (CSVS) and the Australian and New Zealand Society for Vascular Surgery
      (ANZSVS). The survey presented a vignette of a 63-year-old woman with significant
      respiratory co-morbidity and a 54 mm juxtarenal AAA (7 mm neck). There were no
      other adverse morphological features for endovascular repair. The survey included
      images and questions related to management of the aneurysm. RESULTS: 238
      responses were received; 61 from ANZSVS, 65 from CSVS and 112 from VSGBI. VSGBI
      specialists were significantly more likely to continue surveillance than both
      ANZSVS (odds ratio (OR) 3.41, 95% confidence interval (CI) 1.61-7.65; p<0.001)
      and CSVS counterparts (OR 2.61, 95% CI 1.29-5.47; p<0.01). ANZSVS specialists
      were significantly more likely to perform an endovascular repair than those from
      CSVS (OR 3.28, 95% CI 1.50-7.40; p<0.01) and VSGBI (OR 3.65, 95% CI 1.81-7.59;
      p<0.001). CSVS specialists were significantly more likely to manage the aneurysm
      with open surgery than colleagues from the VSGBI (OR 6.57, 95% CI 2.58-18.46;
      p<0.001) and ANZSVS (OR 7.18, 95% CI 2.22-30.79; p<0.001). CONCLUSIONS:
      Significant variation in the management of a juxtarenal AAA between countries was
      observed. The same patient would be more likely to have an endovascular repair in
      Australia and New Zealand, open surgery in Canada and continuing surveillance in
      the UK and Ireland. This variation reflects the lack of long-term evidence and
      international consensus on the optimal management of complex AAA.

PMID- 29363894
TI  - Lutonix(r) 014 DCB global Below the Knee Registry Study: interim 6-month
      outcomes.
AB  - BACKGROUND: The most common clinical presentation of peripheral artery disease
      (PAD) comprises intermittent claudication (IC), but about one third of patients
      will progress to critical limb ischemia (CLI), characterized by rest pain and/or
      tissue loss, which is the most severe limb manifestation of PAD. Paclitaxel
      coated balloons are well established for the endovascular treatment of
      femoropopliteal lesions in patients with IC and CLI. This ongoing multicenter
      registry study is exploring the role of the Lutonix(r) 014 drug-coated balloon
      (DCB) in the treatment of below-the-knee (BTK) arteries and CLI. METHODS: Three
      hundred fourteen (314) patients were enrolled from 26 sites and 12 countries. The
      real-world patients represent those undergoing intervention for BTK arteries with
      the Lutonix(r) 014 DCB. The study had both, primary safety and primary efficacy
      endpoints. The primary safety endpoint was freedom at 30 days from BTK major
      adverse limb event (MALE) + perioperative death (POD). Primary efficacy was
      freedom from clinically driven target lesion reintervention (fTLR) at 6 months.
      Additional secondary endpoints related to safety were reported. RESULTS: The
      interim 6 months' results showed freedom from MALE and POD at 30 days of 98.6%
      and at 6 months (180 days) of 96.0%. Primary efficacy of fTLR at 6 months (180
      days) was 87.9%. Safety related secondary endpoints at 6 months (180 days) showed
      freedom from all of the following: all cause death of 91.2%, above ankle
      amputation 97.1%, reintervention for thrombosis 95.2%, reintervention for distal
      embolization 100.0%, and target vessel revascularization of 88.0%. There were no
      unexpected device or drug related events reported. CONCLUSIONS: The interim 6
      month outcomes demonstrate the safety and efficacy of the Lutonix(r) 014 DCB for
      the treatment of BTK arteries.

PMID- 29363895
TI  - Overview of evidence on emergency carotid stenting in patients with acute
      ischemic stroke due to tandem occlusions: a systematic review and meta-analysis.
AB  - INTRODUCTION: Endovascular intracranial thrombectomy (IT) has established itself
      as the standard of care in treating large-vessel anterior circulation acute
      ischemic stroke (AIS). However, internal carotid artery (ICA) stenosis/occlusion
      hampers distal access and controversy about simultaneous emergency ICA stenting
      ensues. The purpose of this review was to evaluate the safety of emergency ICA
      stenting in combination with IT for AIS with tandem occlusions. To our knowledge
      this is the first meta-analysis to evaluate emergency ICA stenting in tandem
      occlusions, combining results from studies with a control group. EVIDENCE
      ACQUISITION: A systematic review and meta-analysis was conducted according to the
      recommendations of the Preferred Reporting Items for Systematic reviews and Meta-
      Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: A total of 649 potentially
      relevant articles were initially selected. After reviewing at title or abstract
      level, 87 articles were read in full and 23 were included. These studies
      recruited 1000 patients, 220 submitted to IT with no emergency ICA stenting and
      780 to IT and emergency ICA stenting. Successful revascularization (Thrombolysis
      in cerebral infarction scale - TICI>=2b) was achieved in 48.6-100%. Good outcome
      (modified Rankin scale - mRS<=2) ranged from 18.2-100%. Symptomatic intracranial
      haemorrhage (sICH) ranged from 0-45.7% (overall n=168; 17.2%). Mortality at 90
      days ranged from 0-45.4% (overall n=114; 11.7%). Time to recanalization was
      significantly longer in the stenting group with an overall mean difference of
      1.76 (95% Confidence Interval: 1.59-1.93). CONCLUSIONS: In this meta-analysis
      time to recanalization was significantly longer in the emergency ICA stenting
      group. There was no benefit from emergency stenting in parameters such as
      successful revascularization (TICI>=2b), clinical outcome (mRS<=2) or 90-day
      mortality. Data on sICH were scarce. Emergency ICA stenting appears to increase
      time to revascularization and increase the risk of complications with no
      demonstrated clinical benefit. Furthermore, no prospective, randomized controlled
      trials demonstrating relative efficacy and safety of concomitant ICA stenting
      have been published to date. Additional studies must be undertaken to define the
      role of angioplasty and stenting of the extracranial carotid arteries in the
      early management of acute stroke in tandem occlusions. Until then, we recommend
      that ICA stenting concommintant to thrombectomy in acute stroke patients should
      be avoided.

PMID- 29363896
TI  - Usefulness of post mortem computed tomography versus conventional forensic
      autopsy of road accident victims (drivers and passengers).
AB  - Aim of the study: Deaths of in-vehicle victims (drivers and passengers) of road
      accidents represent a significant group of issues addressed by forensic medicine.
      Expressing opinions in this regard involves first of all the determination of the
      cause of death and the forensic pathologist's participation in the process of
      road accident reconstruction through defining the mechanism of bodily harm. The
      scope of the opinion as well as its accuracy and degree of detail largely depend
      on the scope of forensic autopsy. In this context, techniques that broaden the
      capabilities of standard autopsy are of particular importance. This paper
      compares the results of post mortem computed tomography (PMCT) of road accident
      victims (drivers and passengers) against the results of standard examination in
      order to determine the scope to which PMCT significantly enhances autopsy
      capabilities. Material and methods: The analysis covers 118 in-vehicle victims
      (drivers and passengers) examined from 2012 to 2014. In each case, post-mortem
      examination was preceded by PMCT examination using Somatom Emotion 16 (Siemens
      AG, Germany). Results: The results are presented in a tabular form. Conclusions:
      In most road accident victims (drivers and passengers), post mortem computed
      tomography significantly increases the results' degree of detail, particularly
      with regard to injuries of bones and gas collections.

PMID- 29363897
TI  - New challenges in toxicology of new psychoactive substances exemplified by fatal
      cases after UR-144 and UR-144 with pentedrone administration determined by LC-ESI
      MS-MS in blood samples.
AB  - The topic of this paper relates to the study of cases involving the use of new
      psychoactive substances (NPS) from the classes of synthetic cannabinoids and
      cathinones, analyzed from multiple viewpoints including clinical and medico-legal
      perspectives. The paper investigates three fatal cases in which UR-144 and UR-144
      with pentedrone identified in the bodies of victims during post-mortem
      examinations were responsible for the tragic consequences and proved to be the
      indirect cause of death. The victims were men aged 16, 22 and 40 years who used
      drugs, for example they smoked marijuana or its substitutes in the form of
      synthetic cannabinoids. In addition, all of them had behavioural problems. On
      account of emotional imbalance attributable probably to the presence of UR-144
      (in one case) and a mixture of UR-144 and pentedrone (in the other two cases),
      two men committed suicide by jumping from a height and hanging, and one man had
      fatal accidental poisoning with pentedrone which was used to enhance the effect
      of previously used UR-144. The presence of UR-144 and pentedrone in the post
      mortem material was analyzed by liquid chromatography-electrospray ionization
      tandem mass spectrometry (LC-ESI-MS-MS). The results of toxicological tests were
      analyzed with a focus on possible tragic side effects caused by the presence of
      UR-144 and UR-144 with pentedrone in the body.

PMID- 29363898
TI  - Postmortem identification of spermatozoa on human skin based on fluorescent
      monoclonal antibody method.
AB  - Identification of semen residues has relevant consequences, especially for what
      concerns the ascertainment of possible sexual assault. Forensic scientists
      usually focus on the vaginal swab for semen detection despite the importance of
      semen deposition on the skin. Postmortem identification of spermatozoa on
      putrefied human skin is still under investigation. Sperm Hy-LiterTM is an
      antibody technique, used to identify human spermatozoa heads in forensic stains.
      This approach has the potential to eliminate spermatozoa visualization problems
      in a traditional method. Therefore, the present study aimed to compare between
      the traditional method (light microscope and staining via hematoxylin/eosin) and
      a fluorescence-based method (by using fluorescent microscope and staining via
      Sperm Hy-LiterTM) for postmortem identification of spermatozoa on human skin at
      different time intervals. A piece of human skin was divided into three strips;
      the first was a negative control while semen was spread on the second and third
      skin strips. The first (control) and second groups were stained by
      hematoxylin/eosin for light microscopic examinations. The third group was stained
      by Sperm Hy-LiterTM then examined under fluorescent microscope. The results
      revealed that the spermatozoa identifiability was up to 110 days based on Sperm
      Hy-LiterTM and fluorescent microscope, while it was up to 12 days via using
      hematoxylin/eosin and light microscope. Further studies are recommended in order
      to verify not only the accuracy of the used method on skin of dead victims but
      also to evaluate persistence of spermatozoa on different body sites and fabrics.

PMID- 29363899
TI  - A child with imperforate anus for twelve years: a case report of neglect and
      exploitation.
AB  - We report a unique and rare case of child neglect and exploitation and similar
      case was not found. An infant, born with an imperforate anus, underwent surgery
      for a temporary colostomy on the day of birth. Surgery for reversal of colostomy
      with reconstruction was planned at one month of age. However, the guardian did
      not ensure that the child attended for this procedure. Subsequently, at the age
      of 12 years, the child was presented to the emergency unit with an irreducible
      prolapsed colostomy and a life threatening acute abdomen. Emergency laparotomy
      and colostomy reversal were performed with anal reconstruction. The child had
      features of gross neglect and abuse in the form of deprivation of essential
      surgical care, vaccination, and education. He was used for the purpose of begging
      for the financial benefit of his guardian and others. This is a case of neglect
      and exploitation of a child with imperforate anus and it emphasizes the failures
      of the health system to manage and follow-up children with congenital defects
      born to families with a poor socio-economic background.

PMID- 29363900
TI  - 15th Anniversary of the Molecular Techniques Unit at the Department of Forensic
      Medicine at Wroclaw Medical University.
AB  - Molecular Techniques Unit at the Department of Forensic Medicine, Wroclaw Medical
      University has been operating since December 2003. Soon it will be 15 years since
      its establishment. This anniversary become an inspiration to write down the story
      of this institution whose origins illustrate the immense changes that have taken
      place in forensic genetics. The aim of our work was also to consolidate the
      professional achievements of Professor Tadeusz Dobosz, chief of the Unit, one of
      the pioneers of introducing DNA testing technology into Polish forensic medicine.
      The most important achievements of the Unit include participation in two EU
      research projects, the development of a non-destructive method of extraction of
      genetic material, research in field of gene therapy and certification of the
      Laboratory of the Molecular Techniques Unit by the Polish Accreditation Center
      (PCA) confirming compliance with the requirements of the PN-EN ISO/IEC 17025:2005
      standard.

PMID- 29363901
TI  - Dysregulation of Alzheimer's disease-related genes and proteins following cardiac
      arrest.
AB  - <i>Cardiac arrest, usually occurring in the aged population, is the most
      important cause of high morbidity and death in developed countries. Commonly,
      attention, depression, cognitive impairment, spatial memory, short- and long-term
      memory, executive functions, decreased quality of life and social participation
      are disturbed following circulation arrest. Deficits in cognitive function,
      similar to prodromal Alzheimer's disease dementia, following cardiac arrest
      remain an area of concern. Recent research has focused on the post-resuscitation
      period to identify mechanisms of long-term brain damage and cognitive impairment.
      As more patients survive longer periods after cardiac arrest, attention is
      focused on interventions that may enhance cognitive and psychosocial perceptions.
      Here, we review the new data influencing the cognitive and functional outcome in
      the post-resuscitation period.</i>.

PMID- 29363902
TI  - Robust autophagy in optic nerves of experimental Creutzfeldt-Jakob disease and
      Gerstmann-Straussler-Scheinker disease.
AB  - <i>We report here autophagy in the optic nerve in experimental Gerstmann
      Straussler-Scheinker disease (GSS) (Fujisaki-1) in mice and experimental
      Creutzfeldt-Jakob disease (CJD) (Echigo-1) in hamsters. Lesions of both
      experimental GSS in mice and experimental CJD in hamsters were practically
      indistinguishable. Briefly, they consisted of widespread Wallerian degeneration,
      spongiform change and a glial reaction. Numerous axonal swellings were seen. The
      latter were filled with numerous mitochondria and lysosomal electron-dense
      bodies. Autophagic vacuoles defined as structures bound in double membranes were
      readily found in many neuronal processes. The following description is organized
      as a sequence; however, the changes were all observed in the same specimens.
      First several empty double membrane-bound autophagic vacuoles were seen. In
      several of those vacuoles, the inner membrane was separated from the outer
      membrane and enclosed cargo. At the final stage, a mixture of empty autophagic
      vacuoles and electron-dense lysosomal vesicles was seen. Dystrophic neurites
      filled with a mixture of mitochondria, empty autophagic vacuoles and electron
      dense lysosomal vesicles were interpreted as the final stage of autophagy. Of
      note, several areas were replaced with dense astrocytic gliosis.</i>.

PMID- 29363903
TI  - What factors determine phenotype of cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL)? Considerations in the
      context of a novel pathogenic R110C mutation in the NOTCH3 gene.
AB  - <i>We report patients from a Polish family with cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) who
      possess a novel heterozygous R110C mutation in exon 3 of the NOTCH3 gene leading
      to stereotypical cysteine loss. The proband had only seizure attacks and her
      magnetic resonance imaging (MRI) showed very numerous hyperintense foci in the
      cerebral white matter in a location characteristic of CADASIL. Distinctive
      ultrastructural assessment of vessels from skin-muscle biopsy revealed only mild
      degenerative changes but relatively numerous homogeneous deposits of granular
      osmiophilic material (GOM). In the other symptomatic family members with the same
      mutation ischaemic strokes were present but not epilepsy. In the proband's
      affected brother at a similar age, the brain MRI was normal but vessels showed
      pronounced degenerative changes and irregular GOM deposits. The present report
      not only extends the list of known pathogenic mutations responsible for CADASIL
      but also emphasizes clinical and morphologic variability among family members
      with the same NOTCH3 mutation, suggesting that probably additional factors, not
      only mutations, may influence the disease phenotype.</i>.

PMID- 29363904
TI  - Levels of selected pro- and anti-inflammatory cytokines in cerebrospinal fluid in
      patients with hydrocephalus.
AB  - <i>Cytokines are widely known mediators of inflammation accompanying many
      neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is
      caused by impaired cerebrospinal fluid (CSF) absorption and treated by surgical
      shunt insertion. The early diagnosis of NPH is difficult because of various
      manifestations of the disease. One of the most promising research directions is
      biochemical CSF analysis. The aim of this study was to determine the CSF levels
      of cytokines. The levels of various cytokines (IL-6, IL-8, IL-12, IL-10 and TNF
      alpha) were measured in patients with idiopathic active normal pressure
      hydrocephalus, arrested hydrocephalus and hydrocephalus with brain atrophy
      compared to controls. Our study showed that the concentrations of IL-6 and IL-8
      were significantly elevated in the group with idiopathic active hydrocephalus
      compared to control patients. Moreover, we observed that the levels of IL-6 and
      IL-8 in the group with idiopathic active hydrocephalus were significantly higher
      compared to patients with arrested hydrocephalus and hydrocephalus with brain
      atrophy.</i>.

PMID- 29363905
TI  - [Anti-inflammatory effect and mechanisms of Huangqi glycoprotein in treating
      experimental autoimmune encephalomyelitis].
AB  - <i>Huangqi glycoprotein (HQGP) is prepared from Astragalus membranaceus by
      ammonium sulfate precipitation. It was indicated that HQGP has an
      immunoregulatory effect. In this study, we established a chronic experimental
      autoimmune encephalomyelitis (EAE) model and observed the therapeutic effect and
      possible mechanisms of HQGP (intraperitoneally at 1 mg/kg/day) on EAE. The
      results showed that HQGP delayed onset and ameliorated severity of EAE, and
      reduced the infiltration and accumulation of pathogenic T cells in the central
      nerves system (CNS). HQGP also reduced the production of IL-6, IL-17 and TNF
      alpha and increased the level of IL-10. However, the level of IFN-gamma
      production was also increased in HQGP-treated mice compared with EAE control
      mice. In brain, chemokines such as CCL2 and CCL5 were inhibited in HQGP-treated
      EAE compared with control mice. These results demonstrate that HQGP alleviates
      the pathogenesis of EAE possibly by suppressing the neuroinflammation and
      decreasing the secretion of chemokines and cell adhesion.</i>.

PMID- 29363906
TI  - Maternal hypoxia increases hippocampal cell susceptibility to ischemia after
      middle cerebral artery occlusion in rat offspring.
AB  - <i><B>Introduction</B>: Maternal hypoxia induces an adverse uterine environment
      and may induce long-term effects in offspring. This study investigated whether
      maternal hypoxia increases hippocampal cell vulnerability and exacerbates
      neurological impairments in adult rat offspring following ischemia. <B>Material
      and methods</B>: Pregnant Sprague-Dawley rats were randomly assigned to no
      maternal hypoxia or maternal hypoxia treatment groups. Adult male rat offspring
      were subjected to middle cerebral artery occlusion (MCAO). There were four
      groups: maternal + sham (MH + Sham), sham (Sham), maternal hypoxia + MCAO (MH +
      MCAO), and MCAO only (MCAO). Neurological deficits were evaluated. Hippocampal
      cell damage was observed by hematoxylin and eosin (HE) staining. Cell apoptosis
      in the hippocampus was detected by TdT-mediated dUTP-biotin nick-end labeling
      (TUNEL) staining. Caspase-3, cytochrome c, Bax, and bcl-2 expression in the
      hippocampus was detected by Western blot. <B>Results</B>: More severe hippocampal
      cell damage was found in the MH + MCAO group than in the MCAO group.
      Additionally, neurological deficits, percentage of TUNEL positive cells, and
      expression of caspase-3, cytochrome c, and Bax in the hippocampus were
      significantly higher (p < 0.05), whereas bcl-2 expression was significantly lower
      (p < 0.05) in the MH + MCAO group compared to the MCAO group. <B>Conclusions</B>:
      These findings suggest that maternal hypoxia may exacerbate hippocampal cell
      apoptosis in rat offspring after MCAO via alterations in the expression of
      cytochrome c, caspase-3, Bax, and bcl-2, which ultimately affects ischemic stroke
      prognosis. To our knowledge, this is the first study demonstrating that maternal
      hypoxia increases hippocampal cell susceptibility to ischemia in adult rat
      offspring. </i>.

PMID- 29363907
TI  - Effect of dimethyl fumarate on heme oxygenase-1 expression in experimental
      allergic encephalomyelitis in rats.
AB  - <i>Multiple sclerosis (MS) is an autoimmunological disease leading to
      neurodegeneration. The etiology of the disease remains unknown, which strongly
      impedes the development of effective therapy. Most MS treatments focus on
      modulating the activity of the immune system. Dimethyl fumarate (DMF) exerts a
      broad spectrum of action, such as modulating immune cell differentiation towards
      anti-inflammatory subtypes, influencing cytokine production, regulating immune
      cell migration into the central nervous system, and activating intracellular
      antioxidant mechanisms. It is well established that activation of the nuclear
      factor E2 (Nrf2)-dependent pathway, leading to expression of the second-phase
      antioxidant enzymes, is influenced by DMF. In our experiments we used female
      Lewis rats in an animal model of MS - experimental allergic encephalomyelitis
      (EAE). The rats were fed with dimethyl fumarate to test the expression of heme
      oxygenase-1 (HO-1), one of the second-phase antioxidant enzymes, at specific time
      points of the symptomatic phases of the disease: on the first day of the
      occurrence of clinical symptoms (10th day post immunization, DPI); at the peak of
      clinical symptoms (14th DPI); and at the end of the relapse (21st DPI). The
      results showed that HO-1 expression, at both the mRNA and protein level, is
      influenced by DMF administration only at the very beginning of the symptomatic
      phase of EAE, and not at the peak of clinical symptoms, nor at the end of the
      relapse. This indicates that the regulation of the Nrf2-dependent antioxidant
      pathway by DMF occurs at a certain time interval (early EAE/MS) and strongly
      underlines the importance of the earliest introduction of the therapy to the
      patient. </i>.

PMID- 29363908
TI  - Effects of amphetamine administration on neurogenesis in adult rats.
AB  - <i>In our study expression of phospho-(Ser-10)-histone H3 (pH3S10), a marker for
      the early stage of neurogenesis, and cellular early response genes were
      investigated using c-Fos protein as an example of a transcription factor in the
      neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo-
      and exogenous factors, which influence the proliferation potential of progenitor
      cells and accelerate the dendritic development of newborn neurons. D-amphetamine,
      a psychoactive substance, is one of the exogenous factors able to influence the
      process of neurogenesis. The rats were injected with D-amphetamine at a dose of
      1.5 mg/kg/body weight (b.w.) under one administration scheme. Analysis of the
      pH3S10 and c-Fos expression levels in the group of D-amphetamine administered
      rats provided evidence of enhanced expression of these proteins in the regions of
      neurogenesis occurrence in rats. However, conclusions concerning stimulant
      effects of amphetamine on neurogenesis should be formulated with great caution,
      taking into account amphetamine dosage and the administration scheme. It should
      also be remembered that doses of psychoactive substances used in animal models
      can be lethal to humans.</i>.

PMID- 29363909
TI  - Effects of standardized extract of Ferula gummosa root on glutamate-induced
      neurotoxicity.
AB  - <i>Glutamate is one of the major excitatory neurotransmitters in the central
      nervous system. Increasing glutamate leads to neurodegenerative disease.
      Nowadays, plant medicine plays a role in the treatment of some disorders. In this
      research, we investigated the neuroprotective effect of <I>Ferula gummosa</I>
      root extract against glutamate-induced oxidative stress in the rat adrenal
      pheochromocytoma (PC12) and mouse neuroblastoma (N2a) cell lines. The cells were
      pretreated with extract for 2 h and then exposed to glutamate for 24 h. After 24
      h the level of malondialdehyde (MDA), reactive oxygen species (ROS), and
      apoptotic cells were determined in both cell lines. Glutamate increased lipid
      peroxidation, ROS, and apoptotic cells in both cell lines. The extract
      significantly increased the cell viability and decreased the ROS generation under
      glutamate-induced oxidative stress in these cells. Also, the extract decreased
      the MDA level and apoptotic cells. The results showed that <I>Ferula gummosa</I>
      root may have a protective effect on glutamate-induced toxicity, suggesting that
      the extract protects neuronal cells from glutamate-induced oxidative stress.</i>.

PMID- 29363910
TI  - Mast cells as the strength of the inflammatory process.
AB  - The inflammatory process is a complex host defence mechanism aimed at the
      elimination of deleterious factors disturbing homeostasis. Inflammation consists
      of several interdependent stages controlled by a wide range of mediators. Those
      include acute phase proteins, heat shock proteins, complement components,
      biogenic amines, cytokines, lipid-derived mediators, reactive oxygen species,
      nitric oxide, proteolytic enzymes, and kinins. Due to the strategic location in
      the body, mast cells play a protective role in the inflammatory process, through
      its initiation, amplification, and resolution. Mast cells degranulate and/or
      newly produce, and release various mediators classified into three groups:
      preformed mediators, de novo synthesised lipid mediators, and newly synthesised
      cytokines. Those mediators have an impact on different processes occurring during
      inflammation, inter alia, they influence blood vessels leading to dilation,
      enhanced adhesion molecule expression, and increased permeability. Furthermore,
      mast cell mediators play a pivotal role in inflammatory cell chemotaxis,
      degradation of extracellular matrix proteins, impact on stationery cells and
      resolution of inflammation. The release of mast cell mediators and their actions
      constitute a highly complex and still not fully understood mechanism, which
      warrants further studies of the action of mast cells in inflammation. This review
      will focus on the current knowledge concerning the broad role of mast cells in
      the inflammatory process.

PMID- 29363911
TI  - Comparison of clinicopathological features in incidental and nonincidental
      papillary thyroid carcinomas in 308 patients.
AB  - Incidental papillary thyroid carcinomas (IPTCs) consist of a significant portion
      of increasing incidence in papillary thyroid carcinomas. This study investigated
      the clinicopathological features of IPTCs from different perspectives and by
      comparing nonincidental PTCs (NIPTCs) in patients who underwent total
      thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was
      present in 27.9% of 308 patients. IPTCs were significantly accompanied by
      lymphocytic thyroiditis (LT), particularly, multinodular hyperplasia (MNH). IPTCs
      were more common in older patients (51.3 years vs. 47.2 years) and in female
      patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour
      size, lymphatic vessel invasion (2.6% vs. 97.4%), extrathyroidal extension (4.3%
      vs. 95.7%), lymph node metastasis (3.6% vs. 96.4%), multifocality (21.2% vs.
      78.8%), bilaterality (5.3% vs. 94.7%), and BRAFV600 mutation (6.7% vs. 93.3%).
      Older age, bilaterality, encapsulation, and radioactive iodine (RAI) were
      significantly more common in IPTCs > 5 mm than in those <= 5 mm. In conclusion,
      IPTCs are more commonly associated with LT and MNH. IPTCs may have a more
      favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality
      and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may
      have benefits in the management of IPTCs.

PMID- 29363912
TI  - Massively parallel targeted resequencing reveals novel genetic variants
      associated with aspergillosis in paediatric patients with haematological
      malignancies.
AB  - This study aimed to find novel genetic variants of susceptibility to
      aspaergillosis in paediatric patients with haematological malignancies. Complete
      sequences of fifteen genes of human innate immunity (CCL2, CCR2, CD209, CLEC6A,
      CLEC7A and ten TLR genes) were studied in 40 patients diagnosed with
      haematological disorders (20 unaffected and 20 affected by aspergillosis). All
      samples were sequenced with MiSeq (Illumina) and 454 (Roche Diagnostics)
      technologies. Statistical significance of the differences between studied groups
      was determined using the two-tailed Fisher's exact test. Sixty variants of
      potential importance were identified, the vast majority of which are located in
      non-coding parts of the targeted genes. At the threshold of p < 0.000005, one
      intergenic (TLR2 rs4585282) and one intronic variant (CLEC6A rs12099687) were
      found significant between the case and control groups for genotype and allele
      frequencies, respectively. Rs12099687 in CLEC6A was predicted to constitute an
      alternative isoform or cryptic splice site, which potentially changes activity of
      the Dectin-2 protein. Overall, we assume that the two strongest associations
      reported in this study are expected to be reproducible even in the absence of
      other evidence, while another twelve associations may be strong enough to justify
      additional research in larger cohorts.

PMID- 29363913
TI  - Immunohistochemical differentiation between muscularis mucosae and muscularis
      propria for improving the staging of bladder cancer in patients undergoing
      transurethral resection of bladder tumours.
AB  - Microscopic differentiation between muscularis mucosae (MM) and muscularis
      propria (MP) of the bladder in the material obtained during transurethral
      resection (TUR) remains difficult. The study was aimed at determination of the
      usefulness of immunohistochemical staining in this context. Forty-seven TUR
      specimens were stained with 5 mouse anti-human antibodies: anti-desmin, anti
      filamin, anti-type IV collagen, anti-smoothelin, and anti-vimentin. Slides were
      assessed under light microscopy and the intensity of the immune reaction within
      MM and MP was evaluated on a four-level visual scale as follows: negative (0) and
      weakly (1), moderately (2), or strongly (3) positive. MM was identified in 27
      patients (57.4%). The modal values of reaction intensity in MM and MP was 0 and 2
      for desmin (p > 0.05), 2 and 2 for filamin (p = 0.01), 2 and 2 for type IV
      collagen (p > 0.05), 1 and 2 for smoothelin (p = 0.03), and 2 and 0 for vimentin
      (p = 0.02), respectively. Identical intensity within MM and MP was observed in
      7.1%, 28.6%, 20%, 30.1%, 5.6%, respectively. Immunohistochemistry can help
      differentiate between MM and MP in TUR specimens. As of yet, no single marker can
      reliably differentiate between MM and MP; however, a combination of anti-filamin,
      anti-smoothelin, and anti-vimentin antibodies may be reasonable for diagnostic
      purposes.

PMID- 29363915
TI  - Impact of TGF-beta1 expression and -509C>T polymorphism in the TGF-beta1 gene on
      the progression and survival of gastric cancer.
AB  - The aim of this study was to examine the expression of TGF-beta1 and TGF-beta
      receptor type II (RII) and the impact of the -509C>T single nucleotide
      polymorphism (SNP) in the gene in relation to clinicopathological factors in
      gastric cancer (GC). Using immunohistochemistry we investigated 43 patients with
      GC for expression of TGF-beta1 and TGF-beta-RII. Consequently, RFLP-PCR was
      performed to analyze the presence of -509C>T polymorphism in the TGF-beta1 gene.
      We found that 72.1% of GCs had cytoplasmic TGF-beta1 expression and 27.9% were
      negative. The TGF-beta1 receptor type II was expressed on tumor cell membranes in
      58.1%. TGF-beta1 positivity in tumor cytoplasm correlated positively with TGF
      beta1-RII expression in tumor cytoplasm in 67.4% of cases (?2 = 8.02; p = 0.005).
      Also, the results showed that patients with low and moderate tumor
      differentiation had TGF-beta1-RII positivity in 53.3% and 81.8% resp. (?2 = 6.58;
      p = 0,037). The analysis of genotype distribution of the -509C>T SNP in the
      promoter region of TGF-beta1 gene and clinical stage distribution revealed that
      among the 32 patients in III-IV clinical stage 53.1% were heterozygous (TC),
      34.4% were homozygous for the C-allele and 12.5% were homozygous for the variant
      T-allele (?2 = 3.31; p = 0.069). In conclusion the expression of TGF-beta1 was
      related to shorter survival time and rapid progression for the GC patients.
      Additionally, the variant T-allele of the studied polymorphism was associated
      with worse prognosis for GC patients.

PMID- 29363914
TI  - Expression of resistin in the liver of patients with non-alcoholic fatty liver
      disease.
AB  - Adipokines are cytokines that presumably connect the pathologies of metabolic
      syndrome. One of the adipokines is resistin, the role of which in insulin
      resistance, obesity, and non-alcoholic fatty liver disease (NAFLD) needs to be
      determined. Liver biopsy specimens were obtained intraoperatively from 214 obese
      patients. Histological assessment was based on NAFLD activity score according to
      Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry
      assessment of resistin staining and: NAFLD status in obese patients compared with
      a non-obese control group, selected clinical data (age, sex, body mass index -
      BMI), selected biochemical data, comorbidities (hypertension, type 2 diabetes
      mellitus, dyslipidaemia), and metformin treatment in patients with type 2
      diabetes mellitus. Resistin expression was observed in the histiocytes of
      inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the
      hepatocytes with steatosis. There was a positive correlation between the total
      expression of resistin and: (1) NAFLD advancement (NAFLD Activity Score- NAS),
      (2) AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA), LDH,
      GGT, triglycerides (TG), and glycated haemoglobin (HbA1c). Resistin expression
      was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and
      less intense in the control group. Resistin probably plays a role in the
      pathogenesis of hepatic insulin resistance and aggravates pathologic changes in
      the liver of patients with NAFLD.

PMID- 29363916
TI  - The significance of angiogenesis for predicting optimal therapeutic response in
      chronic myeloid leukaemia patients.
AB  - In this study the correlation and the prognostic value of the morphometric
      parameters of angiogenesis for optimal therapeutic response to tyrosine kinase
      inhibitor (TKI) therapy in patients with chronic myeloid leukaemia (CML), i.e.
      complete cytogenetic response (CCgR) and major molecular response (MMoR), were
      investigated. Microvascular density (MVD) and a number of different size- and
      shape-related morphometric parameters of microvessels of bone marrow biopsy from
      40 CML patients and 20 controls were examined. Microvessels of bone marrow were
      examined by using immunohistochemical staining for CD34 and quantified in the
      region of the most intense vascularisation by using image analysis. CML patients
      had significantly higher angiogenesis parameters when compared with controls. A
      statistically significant correlation was found between some parameters of
      angiogenesis and evaluated CCgR and MMoR. For achievement of CCgR, lower values
      of MVD, minor axis, area, circularity, and roundness and higher value of aspect
      ratio, while for achievement of MMoR only lower values of MVD have been
      identified as positive prognostic factors. Besides confirming increased
      angiogenesis in CML patients, this study also demonstrated prognostic
      significance of the degree of angiogenesis for the clinical outcome and
      identified angiogenic predictive factors for achieving optimal response on TKIs
      therapy.

PMID- 29363917
TI  - Research Directions in European Veterinary Pathology in 2010-2016 based on the
      Congresses of the European Society of Veterinary Pathology and the European
      College of Veterinary Pathologists.
AB  - The objective of this paper is to depict the current research directions in
      veterinary pathology in Europe. The analysis was carried out based on the
      abstracts and agendas of the annual European Society of Veterinary Pathology
      (ESVP) congresses organised together with the European College of Veterinary
      Pathologists (ECVP) in 2010-2016. In total, 1444 presentations were evaluated,
      including 41 plenary lectures, 319 short oral presentations, and 1081 posters,
      and in 2016 also three science slams. It was found that infectious and parasitic
      diseases (467 presentations, 32.34%) and oncology (450 presentations, 31.16%)
      were the most commonly discussed topics. Organ pathology was also addressed (327
      presentations, 22.65%), with the subsequent places taken by research on different
      topics (140 presentations, 9.70%) and toxicopathology (67 presentations, 4.64%).
      Among the most commonly presented issues, there was a substantial number of
      presentations on neurology (129 speeches, 8.93%) and mammary gland diseases (101
      presentations, 6.99%). A downward trend was revealed for infectious and parasitic
      diseases and for oncology, and a positive trend for organ pathology, the first
      and the third being statistically significant.

PMID- 29363918
TI  - Intratumoral heterogeneity for inactivating frameshift mutation of CUX1 and SIRT1
      genes in gastric and colorectal cancers.
AB  - Both <I>CUX1</I> and <I>SIRT1</I> are considered tumor suppressor genes (TSGs),
      but it is not known whether <I>CUX1</I> and <I>SIRT1</I> alterations are
      different between high microsatellite instability (MSI-H) and microsatellite
      stable MSI (MSS) cancers. We identified frameshift mutations of <I>CUX1</I> in 4
      cases of colorectal cancer (CRC) and of <I>SIRT1</I> in 1 case of gastric cancer
      (GC) and 3 cases of CRC. All of them were found in GC or CRC with MSI-H (3.5% of
      MSI-H for each gene), but neither in GC nor CRC with MSS. In addition, we
      analyzed intratumoral heterogeneity (ITH) of the <I>CUX1</I> frameshift mutation
      and found that two CRCs (12.5%) harbored regional ITH of the frameshift mutation.
      Our data indicate that there exist frameshift mutations of <I>CUX1</I> and
      <I>SIRT1</I> genes as well as ITH of <I>CUX1</I> frameshift mutation in MSI-H
      cancers, which together might play a role in tumorigenesis of GC and CRC with MSI
      H.

PMID- 29363919
TI  - EWSR1-fusion-negative, SMARCB1-deficient primary pulmonary myxoid sarcoma.
AB  - Primary pulmonary myxoid sarcoma (PPMS) is a recently defined rare neoplasm with
      histological and molecular similarity to extraskeletal myxoid chondrosarcoma. To
      date, 20 cases have been reported. A 48-year-old man presented with a huge mass
      filling the right hemithorax and extending into the tracheobronchial system.
      Histological findings were consistent with PPMS. Immunohistochemistry was
      positive for vimentin, CD10, and EMA, but other lineage-specific markers were
      negative. SMARCB1 (INI1) expression was lost in the tumour cells. FISH analysis
      (<i>EWSR1</i>, <i>FUS</i>, <i>NR4A3</i>, and <i>SMARCB1</i>) revealed no
      abnormalities. This case suggests SMARCB1 loss as a possible alternative
      molecular event driving EWSR1-negative PPMS.

PMID- 29363921
TI  - Answer to the Teresa Pusiol comments to the paper "The association of tumor
      lymphocyte infiltration with clinico-pathological factor and survival in breast
      cancer" by Huszno et al .

PMID- 29363920
TI  - Comments on the article "The association of tumour lymphocyte infiltration with
      clinico-pathological factors and survival in breast cancer" by Huszno et al.

PMID- 29363922
TI  - "Double trouble" - synchronous mantle cell lymphoma and metastatic squamous cell
      carcinoma in an inguinal lymph node.
AB  - Multiple primary neoplasms may also occur synchronously. Lymphoma may coexist
      with second malignant tumor in its primary location or malignant tumor may
      metastases to lymphomatous lymph nodes. Most often lymphoid component is a low
      grade lymphoma and coexistence of mantle cell lymphoma (MCL) and second malignant
      tumor is much rarer. In this report, we describe a case of synchronous squamous
      cell carcinoma and mantle cell lymphoma coexisting in an enlarged inguinal lymph
      node. To the best of our knowledge, this is the second report of synchronous
      metastatic squamous cell carcinoma and MCL in a lymph node.

PMID- 29363923
TI  - Tele-monitoring of a home-based exercise program in amyotrophic lateral
      sclerosis: a feasibility study.

PMID- 29363924
TI  - [Nutritional epigenetics and epigenetic effects of human breast milk].
AB  - The article provides an overview of the current literature on nutritional
      epigenetics. There are currently actively studied hypothesis that nutrition
      especially in early life or in critical periods of the development, may have a
      role in modulating gene expression, and, therefore, have later effects on health
      in adults. Nutritional epigenetics concerns knowledge about the possible effects
      of nutrients on gene expression. Human breast milk is well-known for its ability
      in preventing necrotizing enterocolitis, infectious diseases, and also non
      communicable diseases, such as obesity and related disorders. This paper
      discusses about presumed epigenetic effects of human breast milk and some its
      components. While evidence suggests that a direct relationship may exist of some
      components of human breast milk with epigenetic changes, the mechanisms involved
      are stillunclear.

PMID- 29363925
TI  - [Experimental study of influence of lipophilic products of phytogenic origin on
      lipid metabolism in rats].
AB  - The article presents the results of biochemical evaluation of metabolic effects
      of lipophilic products of plant origin among which such oils as linseed, black
      nuts and walnuts oils as well as medicine "Phosphogliv" were selected as the most
      promising ones. The influence of the studied substances on lipid metabolism in
      experiment on male rats (170-220 g body weight) with modeled acute hepatotoxicity
      with carbon tetrachloride (that was achieved by subcutaneous injection of 50% oil
      solution of carbon tetrachloride - 0.5 ml/100 g of the body mass once a day
      during 3 days) has been investigated. Liver function was assessed by
      triacylglycerols content in the serum, total, esterified and nonesterified
      cholesterol, cholesterol in the lipoproteins of high, low and very low density,
      as well as by the nonesterified cholesterol and phospholipids content in the
      hemolysate of red blood cells. Carbon tetrachloride hepatotoxic damage was
      accompanied by the development of severe hypercholesterolemia associated both
      with the increase in total cholesterol and its content in low density
      lipoproteins alongside the reducing of the cholesterol concentration in high
      density lipoproteins, resulted in secondary dyslipoproteinemia. Inhibition of the
      esterification of cholesterol processes as well as the decrease in the
      triacylglycerols concentration was observed. It is connected with the
      triacylglycerols endogenous synthesis blocking in the liver, resulted from its
      toxic damage. It is also confirmed by cholesterol content reducing in the
      lipoproteins of very low density. In erythrocytes of rats with CCl4 intoxication
      phospholipid content decreased while the amount of nonesterified cholesterol that
      is a component of cell membranes, influencing the proteins and lipids diffusion,
      which reduces the mobility of the fatty acid residues of phospholipids,
      increased. The injection of the black nuts and walnuts oils as well as flax oil
      (intragastric injections 0.2 ml daily in the morning before the main feeding from
      the 7th to the 30th day of the experiment, n=25 in each group) to rats with liver
      failure induced by carbon tetrachloride, contributed to the partial restoration
      of liver tissue structure and statistically reliable decrease of lipid
      metabolism. Decrease in the total cholesterol content by 17.5% in the group of
      animals treated with linseed oil was observed; LDL cholesterol also decreased
      under the influence of walnuts and black nuts oils by 36.7 and 40.6%
      respectively. The increase in the content of phospholipids in erythrocytes of
      rats when administered by the studied lipophilic products has made it possible to
      prove the improvement of the cell membranes rheological properties. The results
      of the study of the influence of linseed, black nuts and walnuts oils as well as
      medicine "Phosphogliv" on animals with hepatotoxicity by CCl4 have proved
      positive effect of these lipophilic substances on lipid metabolism.

PMID- 29363926
TI  - [The effect of microwaves on the fat component and preserve vitamins in foods].

PMID- 29363927
TI  - [Genomic, proteomic and metabolomic predictors of atherosclerosis in obese
      patients. Part II].
AB  - Currently there is no extensive research of metabolic disorders in obese patients
      with atherosclerosis, including the study of genomic, biochemical, immune and
      other markers. Therefore, the aim of the study was to identify the genomic,
      proteomic and metabolic predictors of atherosclerosis in obese patients. We
      evaluated condition of the cardiovascular system of the 100 obese patients aged
      18 to 66 years, which were divided in two groups of patients: Group 1 consisted
      of 50 obese patients without vascular pathology, 2nd group consisted of 50
      patients with obesity, complicated by atherosclerosis. We carried out a study of
      the lipid metabolism and analysis of polymorphic alleles epsilon2, epsilon3,
      epsilon4 of the ApoE gene by PCR. Our data showed that clinically significant
      predictors of atherosclerosis in obese patients are homozygous genotypes
      epsilon2/epsilon2 of the ApoE gene, increased blood serum level of triglycerides,
      oxidated LDL, interleukin-6, adhesion molecules SICAM, L-FABP and adiponectin
      reduction.

PMID- 29363928
TI  - Managing patients with oncologic complications in the emergency department
      [digest].
AB  - As the prevalence of cancer continues to increase in the general population and
      improvements in cancer treatment prolong survival, the incidence of patients
      presenting to the emergency department with oncologic complications will,
      similarly, continue to rise. This issue reviews 3 of the more common
      presentations of oncology patients to the emergency department: metastatic spinal
      cord compression, tumor lysis syndrome, and febrile neutropenia. Signs and
      symptoms of these conditions can be varied and nonspecific, and may be related to
      the malignancy itself or to an adverse effect of the cancer treatment. Timely
      evidence-based decisions in the emergency department regarding diagnostic
      testing, medications, and arrangement of disposition and oncology follow-up can
      significantly improve a cancer patient's quality of life. [Points & Pearls is a
      digest of Emergency Medicine Practice.].

PMID- 29363929
TI  - Best practices in managing child and adolescent behavioral health emergencies
      [digest].
AB  - Behavioral health emergencies most commonly present as depression, suicidal
      behavior, aggression, and severe disorganization. Emergency clinicians should
      avoid relying solely on past medical history or previous psychiatric diagnoses
      that might prematurely rule out medical pathologies. Treatments for behavioral
      health emergencies consist of de-escalation interventions aimed at preventing
      agitation, aggression, and harm. This issue reviews medical pathologies and
      underlying causes that can result in psychiatric presentations and summarizes
      evidence-based practices to evaluate, manage, and refer patients with behavioral
      health emergencies. [Points & Pearls is a digest of Pediatric Emergency Medicine
      Practice].

PMID- 29363930
TI  - [Enrichment of the rats diet with docosahexaenoic acid and astaxanthin:
      physiological and biochemical efficiency].
AB  - To investigate the effect of enrichment of the rats diet with polyunsaturated
      fatty acids (PUFA) omega-3 (220 mg docosahexaenoic acid per 1 kg of animal body
      weight per day) and astaxanthin (5 mg/kg body weight) on serum corticosterone
      concentration, physical fatigue, anxiety of rats after exhausting the load.
      During 30 days the rats of the test group received the diet in which the usual
      fat component comprising sunflower oil and lard (1:1) was completely replaced by
      the mixture of oils (high oleic sunflower (89%), coconut (6%), and marine oil
      from microalgae Schizochytrium sp. (5%) with a high content of docosahexaenoic
      acid with the addition of astaxanthin). Ratio of omega-6 and omega-3 PUFA in the
      lipid component of the experimental diet was 5.2:1 (n=12) and 135:1 in the diet
      of rats in the control group (n=12). DHA enrichment of the diet resulted in a
      significant 10-fold increase of the DHA liver content and omega-6 PUFA reducing
      (in particular of linoleic acid in 2.7-fold). No significant differences have
      been identified between the groups in terms of anxiety, estimated on the elevated
      plus maze at the beginning and on 24th day of the experiment. Results of the
      exhausting load on a treadmill (25th day) showed a significant reduction in
      physical fatigue in rats of the experimental group compared with the control
      group of rats: the number of contacts with the electrical grid was 4.2+/-0.9
      versus 19.7+/-4.4, fulltime shock was 0.9+/-0.2 versus 3.3+/-0.8 sec.
      Significantly lower serum corticosterone concentration took place in the
      subjected to exhausting exertion animals receiving lipid module (15.0+/-3.9
      ng/ml) compared to control animals (31.0+/-5.4 ng/ml). Thus, modification of the
      lipid component of the diet by its enrichment with DHA and astaxanthin led to
      decrease of the rat fatigue during exercise training (test treadmill) and prevent
      from the serum corticosterone raise, that indicates animal stress adaptation
      ability.

PMID- 29363931
TI  - [Impact of new fermented dairy product with whey protein hydrolysate on tolerance
      and dynamics of atopic dermatitis manifestation in children suffering from cow's
      milk protein allergy].

PMID- 29363932
TI  - [Estimation of vitamin status of moscow student according to data on vitamins
      intake and their levels in blood].
AB  - Supply with vitamins C, A, E and B2 of 61 high school students (38 girls and 23
      boys, aged 18-22 years, body mass index - 23.0+/-0.6 kg/m2) by means of
      determination of blood plasma concentration of ascorbic acid, retinol and
      carotenoids, tocopherols and riboflavin has been investigated in the period from
      May to September. All students were well supplied with vitamin C (only 2 boys had
      a reduced level of ascorbic acid) and vitamin A. Decreased level of carotenoids
      was more common in boys (48 versus 24% in girls). 20% of the students were
      insufficiently supplied with vitamin E, 38% - with vitamin B2. 39% of students
      (50% girls and 22% boys) were adequately provided with all studied vitamins. 5%
      of the students had a combined deficiency of 3 vitamins, 20% - 2 vitamins.
      Student's sufficiency with vitamins B2, C, A, E, carotenoids did not depend on
      the season. Diet intake of vitamins C, A, carotenoids and vitamin B2 has been
      calculated basing on the data on the frequency of food consumption during the
      previous month. Reduced consumption relatively to the Russia RDA of vitamins V2,
      C and A took place in 63, 54 and 46% of the students respectively. The lack of
      vitamin B2 in the diet was most pronounced, the value of probabilistic risk
      corresponded to the average level in 34% of students. Average probabilistic risk
      of inadequate intake of vitamin A was present in 17% of students, vitamin C - 6%.
      Coincidence of the results of vitamin C and A status assessment obtained by
      calculation of vitamin diet intake and by biochemical methods (concentration of
      vitamins in the blood plasma) was 94 and 83%. These methods are interchangeable
      if you select the value of the average probability of risk failure intake of
      these vitamins as a criterion. Proportion of coinciding results of the estimation
      of vitamin B2 status was 56%. Special well-designed studies on larger sample
      surveyed are needed for the final output of the interchangeability of methods to
      assess riboflavin status.

PMID- 29363934
TI  - The ratio of ubiqiunon redox forms in the liver mitochondria under toxic
      hepatitis induced on the background of alimentary protein deficiency.
AB  - The level of the total ubiqiunon and redox forms CoQ in the rat liver
      mitochondria under the conditions of alimentary protein deficiency and toxic
      hepatitis, induced on the background protein deficiency has been investigated.
      Research has been carried out on 36 white non-linear rats, divided into 4 groups:
      1 - rats, maintained on the complete semisynthetic ration; 2 - rats, fed low
      protein ration; 3 - rats with acute acetaminophen-induced hepatitis, maintained
      on complete ration; 4 - rats with acetaminophen-induced hepatitis, maintained
      under the conditions of protein deficiency. The content of total and oxidized
      ubiqiunon was determined spectrophotometrically at lambda=275 nm (molar
      extinction coefficient 12.25 Mm-1*sm-1). Reduced ubiqiunon content was determined
      by the difference between total and oxidized ubiqiunon content. The amount of
      tyrosine in the liver was measured in deproteinised by 6% sulfosalicylic acid
      extracts of liver tissue on an automated amino acid analyzer. The decrease of the
      total ubiqiunon content in liver mitochondria by 35% on the background of 2-fold
      decrease of oxidized ubiqiunon and preservation of reduced ubiqiunon amount has
      been estimated under the conditions of low-protein diet. Simultaneously the 5
      fold decrease of liver content of tyrosine - the ubiqiunon precursor - has been
      observed. It has been shown, that under the conditions of acetaminophen-induced
      hepatitis the content of total ubiqiunon and its redox forms in the liver
      mitochondria of rats fed complete diet didn't change significantly comparing to
      control. A decrease of total ubiqiunon by 60% on the background of acute (18
      fold) decrease of reduced ubiqiunon in liver mitochondria of rats with hepatitis,
      fed low-protein diet, has been observed. Established changes of the content of
      redox ubiquinone forms (a key component of the oxidative phosphorylation system
      in the liver mitochondria) can be considered as one of the mechanisms of
      malfunction of energy biotransformation system under the conditions of toxic
      liver injury in animals with protein deficiency.

PMID- 29363933
TI  - [Sontamination of baby foods with ochratoxin A].
AB  - Mycotoxin ochratoxin A (OTA) is a widespread contaminant of raw cereal grains
      with nephrotoxic activity. Sereal-based baby foods (BF) are an important
      component of the infant diet. In Russia, the presence of OTA in grainbased BF is
      not allowed (<0.5 ng/kg), in the EU maximum limit of toxin in BF is 0.5 ng/kg.
      The Joint FAO/WHO Expert Committee on Food Additives (JECFA) set for OTA a
      provisional tolerable weekly intake of 100 ng/kg bw; the European Food Safety
      Authority (EFSA) - 120 ng/kg bw. The purpose of this study was to investigate the
      OTA content in BF (infant cereals and canned food) and assess the relevant risk
      to the health of children first year of life. The analysis of OTA was performed
      by immunoaffinity column clean-up and high performance liquid chromatography with
      fluorescence detection. The limit of detection and limit of quantification for
      OTA were 0.10 and 0.50 ng/kg, respectively. The content of OTA in BF was
      represented as maximum (Max), mean (M), median (Me) and 90 percentile (90%) of
      all samples. The 554 BF samples based on corn, rice, buckwheat, millet, wheat,
      oats, barley, and mixtures of cereals were studied. OTA was detected in 32
      samples of BF: in 30 of the 312 samples of infant cereals (Max - 4.95 ng/kg; M -
      0.09 ng/kg, Me and 90% - 0 ng/kg) and in 2 of the 242 samples of canned food
      (0.34 and 0.37 ng/kg). 20 samples of BF were contaminated with OTA above the
      maximum limit (>=0.50 ng/kg). BF, exhibited the highest incidence of OTA, were
      buckwheat-based (13 of 41 samples, Max - 2.52 ng/kg, M - 0.36 ng/kg, Me - 0
      ng/kg, 90% - 1.57 ng/kg) and mixed-grain (12 of 115 samples, Max - 4.95 ng/kg, M 
      0.10 ng/kg, Me - 0 ng/kg, 90% - 0.14 ng/kg) infant cereals. OTA was also
      detected in 2 of 40 samples of oat-based infant cereals (0.19 and 0.60 ng/kg), in
      2 of 72 samples of rice-based infant cereals (0.18 and 0.48 ng/kg) and in 1 of 37
      samples of wheat-based infant cereals (0.13 ng/kg). None of the 4 samples of corn
      based and of the 3 samples of millet-based infant cereals contained OTA.
      Calculations showed that for infants the daily ochratoxin A dietary intake did
      not exceed 6.8 ng/kg bw. This value of OTA intake is below the levels, proposed
      as tolerable intake. Thus, one can conclude that cereal-based BF (infant cereals
      and canned food) are moderately contaminated with OTA and there is not a
      significant toxicological risk to the health of children of first year of life.
      However, identification of BF samples containing OTA above the maximum limit,
      demonstrates the need for thorough monitoring of the quality of the products from
      the manufacturers and regulatory authorities.

PMID- 29363935
TI  - Doxorubicin-Conjugated Heparin-Coated Superparamagnetic Iron Oxide Nanoparticles
      for Combined Anticancer Drug Delivery and Magnetic Resonance Imaging.
AB  - In this study, superparamagnetic iron oxide (SPIO) nanoparticles (NPs) with an
      average size of 10+/-2 nm were coated with doxorubicin (Dox)-conjugated heparin
      (DH-SPIO) and were used for targeted anticancer drug delivery, and as a magnetic
      resonance imaging (MRI) contrast agent. The DH-SPIO NPs had a mean particle size
      of 125+/-10 nm and a zeta potential of -35+/-3 mV. Fourier transform-infrared
      spectroscopy, X-ray diffraction spectroscopy, transmission electron microscopy,
      vibrating sample magnetometry, and MTT assay were used to investigate the
      properties of DH-SPIO NPs. The internalization of DH-SPIO NPs into A549 tumor
      cells was examined using fluorescence microscopy and quantified by flow
      cytometry. Prussian blue staining, total iron assay, in vitro MRI and
      transmission electron microscopy showed that DH-SPIO NPs had high
      superparamagnetic clustering effect. In vivo therapy of A549 human lung
      carcinoma, DHSPIO NPs displayed a higher efficacy than Dox in inhibiting tumor
      growth and prolonging the survival of mice bearing tumors. Meanwhile, the
      pathological damage to the cardiac tissue in mice treated with DH-SPIO NPs was
      significantly less severe than that of mice treated with free Dox at the same
      dosage. These results show that DH-SPIO NPs are promising biomaterials for
      combined drug therapy and clinical imaging.

PMID- 29363936
TI  - Doxorubicin Hydrochloride-Loaded Mesoporous Silica Nanoparticles Inhibit Non
      Small Cell Lung Cancer Metastasis by Suppressing VEGF-Mediated Angiogenesis.
AB  - Mesoporous silica nanoparticles (MSNs) are widely used nanoparticles with a pore
      rich structure that is suitable for drug delivery. Here, we used MSNs to carry
      and deliver doxorubicin hydrochloride (DOX) in vivo to study the features of
      DOXloaded MSNs (MSNs@DOX). We used TEM and zeta potential to illustrate that
      MSNs@DOX increase apoptosis and decrease metastasis of tumor cells. We used MTT,
      flow cytometry, Western blotting, wound healing, and transwell assays, as well as
      an in vivo metastasis model to explore the anti-carcinoma efficacy of MSNs@DOX.
      Our results showed that DOX was efficiently loaded into MSNs measuring
      approximately 88+/-11 nm, which significantly increased the antitumor efficacy of
      DOX on lung cancer, both in vitro and in vivo, compared to a regular DOX
      treatment. MSNs@DOX markedly induced apoptosis through cytochrome C release and
      the caspase family. Furthermore, cell migration and invasion were sharply
      inhibited, both in vitro and in vivo. We also found that the enhanced effect of
      MSNs@DOX might be due to an increased cellular uptake by tumor cells based on the
      enhanced permeability and retention time of the nanoparticles. Matrigel plug
      assays and Western blotting assays revealed that the molecular mechanism behind
      the anti-metastasis effect might be attributed to the suppression of VEGF
      mediated angiogenesis. Our results offer a new perspective on the application of
      nanoparticles against metastasis.

PMID- 29363937
TI  - Detection of Circulating Tumor Cells Using Microfluidics.
AB  - Metastasis is the main cause of death in cancer patients worldwide. During
      metastasis, cancer cells detach from the primary tumor and invade distant tissue.
      The cells that undergo this process are called circulating tumor cells (CTCs).
      Studies show that the number of CTCs in the peripheral blood can predict
      progression-free survival and overall survival and can be informative concerning
      the efficacy of treatment. Research is now concentrated on developing devices
      that can detect CTCs in the blood of cancer patients with improved sensitivity
      and specificity that can lead to improved clinical evaluation. This review
      focuses on devices that detect and capture CTCs using different cell properties
      (surface markers, size, deformability, electrical properties, etc.). We also
      discuss the process of tumor cell dissemination, the biology of CTCs, epithelial
      mesenchymal transition (EMT), and several challenges and clinical applications of
      CTC detection.

PMID- 29363938
TI  - Universal mRNA Translation Enhancement with Gold Nanoparticles Conjugated to
      Oligonucleotides with a Poly(T) Sequence.
AB  - DNA-conjugated gold nanoparticles (AuNPs) have been shown to enhance the
      translation of mRNA. However, the specific sequence on the DNA dictates the
      specific mRNA to be enhanced. This study describes poly(thymine)-functionalized
      AuNPs (AuNP-p(T)DNA) capable of enhancing the translation of any mRNA template
      that is incorporated into pcDNA6 vector with bovine growth hormone (BGH)
      polyadenylation signal (P(A)). We demonstrated this by incorporating four genes:
      green fluorescence protein (GFP), general control nonderepressible 5 (GCN5), cAMP
      responsive element binding protein 1 (CREB1), and X-box-binding protein 1-spliced
      (XBP-1S) separately into pcDNA6 vector with BGH P(A) before their expression in
      HeLa lysate. The addition of AuNP-p(T)DNA to HeLa lysate containing GFP, GCN5,
      CREB1, and XBP-1S mRNA increased protein synthesis 1.80, 1.99, 1.95, and 2.20
      times, respectively. Similar translation enhancement was also observed in a
      multiplex reaction containing the mRNA of three genes together in the lysate.
      Complementary p(T)DNA hybridization to the poly(A) tail of the mRNA was critical
      as the removal of either p(T)DNA or BGH P(A) in XBP-1S mRNA or the replacement of
      p(T)DNA with p(A)DNA reduced the translation back to baseline level. Finally, an
      optimum length of 25 nucleotides for the DNA oligomer and a AuNP-p(T)DNA:mRNA
      ratio of 0.658 achieved a 3.08-fold translation enhancement. The AuNP-p(T)DNA
      nanoconstruct could be incorporated into commercial cell-free protein synthesis
      kits as a universal translation enhancer.

PMID- 29363939
TI  - Bad Behavior: Improving Reproducibility in Behavior Testing.
AB  - Systems neuroscience research is increasingly possible through the use of
      integrated molecular and circuit-level analyses. These studies depend on the use
      of animal models and, in many cases, molecular and circuit-level analyses.
      Associated with genetic, pharmacologic, epigenetic, and other types of
      environmental manipulations. We illustrate typical pitfalls resulting from poor
      validation of behavior tests. We describe experimental designs and enumerate
      controls needed to improve reproducibility in investigating and reporting of
      behavioral phenotypes.

PMID- 29363940
TI  - N-Myristoylation as a Drug Target in Malaria: Exploring the Role of N
      Myristoyltransferase Substrates in the Inhibitor Mode of Action.
AB  - Malaria continues to be a significant cause of death and morbidity worldwide, and
      there is a need for new antimalarial drugs with novel targets. We have focused as
      a potential target for drug development on N-myristoyl transferase (NMT), an
      enzyme that acylates a wide range of substrate proteins. The NMT substrates in
      Plasmodium falciparum include some proteins that are common to processes in
      eukaryotes such as secretory transport and others that are unique to apicomplexan
      parasites. Myristoylation facilitates a protein interaction with membranes that
      may be strengthened by further lipidation, and the inhibition of NMT results in
      incorrect protein localization and the consequent disruption of function. The
      diverse roles of NMT substrates mean that NMT inhibition has a pleiotropic and
      severe impact on parasite development, growth, and multiplication. To study the
      mode of action underlying NMT inhibition, it is important to consider the
      function of proteins upstream and downstream of NMT. In this work, we therefore
      present our current perspective on the different functions of known NMT
      substrates as well as compare the inhibition of cotranslational myristoylation to
      the inhibition of known targets upstream of NMT.

PMID- 29363941
TI  - Heterologous Production and Purification of a Functional Chloroform Reductive
      Dehalogenase.
AB  - Reductive dehalogenases (RDases) are key enzymes involved in the respiratory
      process of anaerobic organohalide respiring bacteria (ORB). Heterologous
      expression of respiratory RDases is desirable for structural and functional
      studies; however, there are few reports of successful expression of these
      enzymes. Dehalobacter sp. strain UNSWDHB is an ORB, whose preferred electron
      acceptor is chloroform. This study describes efforts to express recombinant
      reductive dehalogenase (TmrA), derived from UNSW DHB, using the heterologous
      hosts Escherichia coli and Bacillus megaterium. Here, we report the recombinant
      expression of soluble and functional TmrA, using B. megaterium as an expression
      host under a xylose-inducible promoter. Successful incorporation of iron-sulfur
      clusters and a corrinoid cofactor was demonstrated using UV-vis spectroscopic
      analyses. In vitro dehalogenation of chloroform using purified recombinant TmrA
      was demonstrated. This is the first known report of heterologous expression and
      purification of a respiratory reductive dehalogenase from an obligate
      organohalide respiring bacterium.

PMID- 29363942
TI  - Multi-Stimuli-Responsive Fluorescence Switching from a Pyridine-Functionalized
      Tetraphenylethene AIEgen.
AB  - The discovery of the striking aggregation-induced emission (AIE) phenomenon has
      opened a new avenue for smart light-emitting materials. Herein, a new AIE
      luminogen (AIEgen), 1,1,2,2-tetrakis(4-((E)-2-(pyridin-2-yl)vinyl)phenyl)ethene
      (TP2VPE), has been designed and synthesized by introducing the vinylpyridine
      motifs into the tetraphenylethene backbone. The emission spectrum of the new
      obtained AIEgen crystalline material can be switched in response to not only
      mechanical grinding and hydrostatic compression but also the protonation effect
      with excellent reversibility and reproducibility. Single-crystal X-ray structural
      analysis disclosed the supramolecular porous channel structure, which provides a
      shrinkable volume to maintain the fluorescence emission upon high pressure.
      Furthermore, protonation-deprotonation of the pyridine moieties in TP2VPE has a
      significant effect on the frontier molecular orbitals as well as very distinctive
      emission characteristics upon acid and base stimuli. The dual-response
      performance and the ease of its preparation and renewal endow the material with
      potential applications in pressure and acid/alkali fluorescence sensing.

PMID- 29363943
TI  - Photothermally Amplified Therapeutic Liposomes for Effective Combination
      Treatment of Cancer.
AB  - Near-infrared photothermal therapy has been investigated extensively with regard
      to selective tumor eradication, yet its clinical translation has been limited
      because of the absence of FDA-approvable agents with effective phototherapeutic
      function and minimal systemic toxicity. In this work, we developed photothermally
      amplified therapeutic liposomes in an attempt to synergize chemotherapy and
      hyperthermia for effective cancer phototherapy. The anticancer drug cisplatin and
      the photothermal agent indocyanine green (ICG) were encapsulated in a
      thermosensitive liposomal formulation at the lipid/ICG ratio maximizing the ICG
      loading efficiency. These liposomes released cytotoxic cisplatin molecules
      selectively via ICG-mediated photothermal stimulation. In phototherapeutic
      studies, these liposomes amplified therapeutic effects both in vitro in cancer
      cells and in vivo in mouse tumor models significantly over chemotherapy or
      photothermal therapy alone. We believe that these photothermally amplified
      therapeutic liposomes composed solely of already FDA-approved components
      (cisplatin, ICG, and phospholipids) have enormous potential for clinical
      translation in treating various tumors compatible with laser irradiation.

PMID- 29363945
TI  - Sortase-Mediated High-Throughput Screening Platform for Directed Enzyme
      Evolution.
AB  - Sortase-catalyzed ligations have emerged as powerful tools for the site-specific
      ligation of peptides and proteins in material science and biocatalysis. In this
      work, a directed sortase evolution strategy (SortEvolve) has been developed as a
      general high-throughput screening (HTS) platform to improve activity of sortase A
      (application 1) and to perform directed laccase evolution through a
      semipurification process in 96-well microtiter plate (MTP) (application 2). A
      semipurification process in polypropylene MTP (PP-MTP) is achieved through the
      anchor peptide LCI, which acts as adhesion promoter. To validate the SortEvolve
      screening platform for both applications, three site-saturation mutagenesis (SSM)
      libraries of sortase A (Sa-SrtA) from Staphylococcus aureus (application 1) and
      two SSM libraries of the copper efflux oxidase (CueO laccase) from Escherichia
      coli (application 2) were generated at literature reported positions. After
      screening and rescreening, an array of Sa-SrtA variants (including the previously
      reported P94S, D160N, and D165A) and CueO variants (including the previously
      reported D439A and P444A) were identified. Further recombinant Sa-SrtA variant
      P94T/D160L/D165Q and CueO variant D439V/P444V were characterized with 22-fold and
      103-fold improvements in catalytic efficiency compared with corresponding wild
      types, respectively. An important advantage of the SortEvolve screening platform
      in comparison to many MTP-based screening systems is that the background noise
      was minimized (decreased 20-fold; application 2) due to the employed
      semipurification process. In essence, SortEvolve provides a universal surface
      functionalized screening platform for sortases and enzymes in which especially
      background activity can be minimized to enable successful directed evolution
      campaigns.

PMID- 29363944
TI  - Structure-Activity Relationship Studies of a Macrocyclic AGRP-Mimetic Scaffold
      c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-DPro] Yield Potent and Selective Melanocortin-4
      Receptor Antagonists and Melanocortin-5 Receptor Inverse Agonists That Increase
      Food Intake in Mice.
AB  - The melanocortin system has five receptors, and antagonists of the central
      melanocortin receptors (MC3R, MC4R) are postulated to be viable therapeutics for
      disorders of negative energy balance such as anorexia, cachexia, and failure to
      thrive. Agouti-related protein (AGRP) is an antagonist of the MC3R and an
      antagonist/inverse agonist of the MC4R. Biophysical NMR-based structural studies
      have demonstrated that the active sequence of this hormone, Arg-Phe-Phe, is
      located on an exposed beta-hairpin loop. It has previously been demonstrated that
      the macrocyclic octapeptide scaffold c[Pro1-Arg2-Phe3-Phe4-Asn5-Ala6-Phe7-DPro8]
      is 16-fold less potent than AGRP at the mouse MC4R (mMC4R). Herein it was
      hypothesized that the Phe7 position may be substituted to produce more potent
      and/or selective melanocortin receptor antagonist ligands based on this template.
      A 10-membered library was synthesized that substituted small (Gly), polar (Ser),
      acidic (Asp), basic (Lys), aliphatic (Leu, Nle, and Cha), and aromatic (Trp, Tyr,
      hPhe) amino acids to explore potential modifications at the Phe7 position. The
      most potent mMC4R antagonist contained a Nle7 substitution, was equipotent to the
      lead ligand 200-fold selective for the mMC4R over the mMC3R, and caused a
      significant increase in food intake when injected intrathecally into male mice.
      Three compounds possessed sigmoidal dose-response inverse agonist curves at the
      mMC5R, while the remaining seven decreased cAMP production from basal levels at a
      concentration of 100 MUM. These findings will add to the knowledge base toward
      the development of potent and selective probes to study the role of the
      melanocortin system in diseases of negative energy balance and can be useful in
      the design of molecular probes to examine the physiological functions of the
      mMC5R.

PMID- 29363946
TI  - Silver Nanoclusters Encapsulated into Metal-Organic Frameworks with Enhanced
      Fluorescence and Specific Ion Accumulation toward the Microdot Array-Based
      Fluorimetric Analysis of Copper in Blood.
AB  - Silver nanoclusters (AgNCs) were first coated with bovine serum albumin (BSA) and
      then encapsulated into porous metal-organic frameworks of ZIF-8 by the protein
      mediated biomineralization process. Unexpectedly, the fluorescence intensities of
      the yielded AgNCs-BSA@ZIF-8 nanocomposites were discovered to be continuously
      enhanced during each of the BSA coating and ZIF-8 encapsulation steps. Compared
      to common AgNCs, greatly improved photostability and storage stability of AgNCs
      could also be expected. More importantly, having benefited from the ZIF-8 shells,
      the prepared nanocomposites could possess the specific accumulation and sensitive
      response to Cu2+ ions, resulting in the rational quenching of their fluorescence
      intensities. Moreover, AgNCs-BSA@ZIF-8 nanocomposites were coated onto the
      hydrophobic arraying slides toward a microdots array-based fluorimetric method
      for the fast and sensitive evaluation of Cu2+ ions. It was discovered that the
      developed fluorimetric strategy could ensure the high-throughput analysis of Cu2+
      ions in wide pH range, and especially some harsh and high-salt media. It can
      allow for the detection of Cu2+ ions in blood with the concentrations ranging
      from 4.0 * 10-4 to 160 MUM, thus serving as a new copper detection candidate to
      be widely applied in clinical test, food safety, and environmental monitoring
      fields.

PMID- 29363947
TI  - Probing the Mechanism for Bipolar Resistive Switching in Annealed Graphene Oxide
      Thin Films.
AB  - The bipolar resistive switching (BRS) between a metallic low resistance state
      (LRS) and an insulating high resistance state (HRS) is demonstrated for annealed
      graphene oxide (GO) thin film-based device structures with aluminum (Al) as one
      of the contact electrodes. An optimal switching of ~104 order is recorded for
      Al/GO (200  degrees C)/indium tin oxide (ITO) among the device structures in
      metal (M2)/GO (T)/metal (M1) configurations (M1 = Al, Au, or ITO and M2 = Au or
      Al), fabricated using GO (T)/metal (M1), annealed at different temperatures, T =
      100, 200, 300, and 400  degrees C. The initial Ohmic conduction for electronic
      transport and the presence of metal contents through GO thin films in the X-ray
      photoelectron spectroscopy support the physical evidence of Al filament formation
      between the two electrodes as imaged by the high-resolution transmission electron
      microscopy. The speculated mechanism for BRS in repeated voltage sweep cycles is
      attributed to the current triggered breaking of metal filaments because of the
      combined effect of Joule's heating and Peltier heat generation at LRS -> HRS
      transition, and electric field induced migration of metal atoms, leading to the
      formation of metal filaments through the GO film at the HRS -> LRS transition.
      The higher switching ratio exhibited in the current study could be translated to
      engineer simple and low-cost resistive memory devices.

PMID- 29363948
TI  - Electrochemical Sensor Coating Based on Electrophoretic Deposition of Au-Doped
      Self-Assembled Nanoparticles.
AB  - The electrophoretic deposition (EPD) of self-assembled nanoparticles (NPs) on the
      surface of an electrode is a new strategy for preparing sensor coating. By simply
      changing the deposition conditions, the electrochemical response for an analyte
      of deposited NPs-based coating can be controlled. This advantage can decrease the
      difference between different batches of sensor coating and ensure the
      reproducibility of each sensor. This work investigated the effects of deposition
      conditions (including deposition voltage, pH value of suspension, and deposition
      time) on the structure and the electrochemical response for l-tryptophan of
      sensor coating formed from Au-doped poly(sodium gamma-glutamate) with pendant
      dopamine units nanohybrids (Au/gamma-PGA-DA NBs) via the EPD method. The
      structure and thickness of the deposited sensor coating were measured by atomic
      force microscopy, which demonstrated that the structure and thickness of coating
      can be affected by the deposition voltage, the pH value of the suspension, and
      the deposition time. The responsive current for l-tryptophan of the deposited
      sensor coating were measured by differential pulse voltammetry, which showed that
      the responsive current value was affected by the structure and thickness of the
      deposited coating. These arguments suggested that a rich design-space for tuning
      the electrochemical response for analyte and a source of variability in the
      structure of sensor coating can be provided by the deposition conditions. When
      Au/gamma-PGA-DA NBs were deposited on the electrode surface and formed a
      continuous coating with particle morphology and thinner thickness, the deposited
      sensor coating exhibited optimal electrochemical response for l-tryptophan.

PMID- 29363949
TI  - Fluorescence Regulation of Copper Nanoclusters via DNA Template Manipulation
      toward Design of a High Signal-to-Noise Ratio Biosensor.
AB  - Because of bioaccumulation of food chain and disability of biodegradation,
      concentration of toxic mercury ions (Hg2+) in the environment dramatically varies
      from picomolar to micromolar, indicating the importance of well-performed Hg2+
      analytical methods. Herein, reticular DNA is constructed by introducing thymine
      (T)-Hg2+-T nodes in poly(T) DNA, and copper nanoclusters (CuNCs) with aggregate
      morphology are prepared using this reticular DNA as a template. Intriguingly, the
      prepared CuNCs exhibit enhanced fluorescence. Meanwhile, the reticular DNA
      reveals evident resistance to enzyme digestion, further clarifying the
      fluorescence enhancement of CuNCs. Relying on the dual function of DNA
      manipulation, a high signal-to-noise ratio biosensor is designed. This analytical
      approach can quantify Hg2+ in a very wide range (50 pM to 500 MUM) with an
      ultralow detection limit (16 pM). Besides, depending on the specific interaction
      between Hg2+ and reduced l-glutathione (GSH), this biosensor is able to evaluate
      the inhibition of GSH toward Hg2+. In addition, pollution of Hg2+ in three lakes
      is tested using this method, and the obtained results are in accord with those
      from inductively coupled plasma mass spectrometry. In general, this work provides
      an alternative way to regulate the properties of DNA-templated nanomaterials and
      indicates the applicability of this way by fabricating an advanced biosensor.

PMID- 29363951
TI  - Mapping Global Flows of Chemicals: From Fossil Fuel Feedstocks to Chemical
      Products.
AB  - Chemical products are ubiquitous in modern society. The chemical sector is the
      largest industrial energy consumer and the third largest industrial emitter of
      carbon dioxide. The current portfolio of mitigation options for the chemical
      sector emphasizes upstream "supply side" solutions, whereas downstream mitigation
      options, such as material efficiency, are given comparatively short shrift. Key
      reasons for this are the scarcity of data on the sector's material flows, and the
      highly intertwined nature of its complex supply chains. We provide the most up to
      date, comprehensive and transparent data set available publicly, on virgin
      production routes in the chemical sector: from fossil fuel feedstocks to chemical
      products. We map global mass flows for the year 2013 through a complex network of
      transformation processes, and by taking account of secondary reactants and by
      products, we maintain a full mass balance throughout. The resulting data set
      partially addresses the dearth of publicly available information on the chemical
      sector's supply chain, and can be used to prioritise downstream mitigation
      options.

PMID- 29363952
TI  - Dinuclear Iron(III) and Cobalt(III) Complexes Featuring a Biradical Bridge: Their
      Molecular Structures and Magnetic, Spectroscopic, and Redox Properties.
AB  - Bis-bidentate ligand H4LB featuring two o-amidophenol noninnocent units was used
      to synthesize novel binuclear complexes [(LR)MIII(*LB*)MIII(LR)](ClO4)2, M = Fe
      (1) and Co (2, 3), with HLR (R = CH3, Cl) being the facially coordinating
      tetradentate coligands. Upon the synthesis, the fully reduced amidophenolate form
      of the ligand (LB)4- becomes oxidized, resulting in the formation of a rare
      example of a biradical (*LB*)2- bridge connecting two metal ions, as supported by
      X-ray crystallography. The electronic structures of the complexes have been
      probed by Mossbauer spectroscopy, magnetic susceptibility measurements, and
      electron paramagnetic resonance (EPR) spectroscopy. Species 1 contains two high
      spin Fe(III) ions (S = 5/2) each coupled strongly antiferromagnetically (|J| >
      150 cm-1; H = -2JS1S2) with a semiquinone pi-radical (S = 1/2) form of the
      bridging (*LB*)2- ligand. The effective S = 2 spins of each [Fe(III)+R?]
      monomeric unit are then weakly ferromagnetically coupled with J = +0.22 cm-1.
      Species 2 and 3 reveal very similar electronic structures: the low-spin Co(III)
      ion is diamagnetic, which leaves the two-spin carriers at the bridging (*LB*)2-
      biradical to display an isotropic EPR signal at g = 1.995 for 2 (1.993 for 3) in
      solution at room temperature and in the frozen state with no hyperfine structure.
      The weak half-field signal at g = 3.988 for 2 (3.978 for 3) was also observed at
      17 K for the spin-forbidden |DeltaMS| = 2 transition due to ferromagnetically
      coupled S = 1/2 spins (J = +47 cm-1) of the bridging biradical. The compounds
      show rich electrochemistry, displaying two (1) or four (2, 3) one-electron
      reversible processes. Normal and differential pulse voltammetry as well as
      constant potential coulometry, combined with EPR experiments, confirmed that the
      observed electron transfers are all localized at the bridging noninnocent (*LB*)2
      ligand.

PMID- 29363954
TI  - Sounding Out Dysfunctional Oxygen Metabolism: A Small-Molecule Probe for
      Photoacoustic Imaging of Hypoxia.

PMID- 29363953
TI  - Iridium(III)-Based Metal-Organic Frameworks as Multiresponsive Luminescent
      Sensors for Fe3+, Cr2O72-, and ATP2- in Aqueous Media.
AB  - Three iridium(III)-based metal-organic frameworks (MOFs), namely [Cd3{Ir(ppy
      COO)3}2(DMF)2(H2O)4].6H2O.2DMF (1), [Cd3{Ir(ppy-COO)3}2(DMA)2(H2O)2].0.5H2O.2DMA
      (2), and [Cd3{Ir(ppy-COO)3}2(DEF)2(H2O)2].8H2O.2DEF (3) (ppy-COOH = methyl-3
      (pyridin-2-yl)benzoic acid, DMF = N,N-dimethylformamide, DMA = N,N
      dimethylacetamide, DEF = N,N-diethylformamide), have been synthesized and
      characterized. Single-crystal structural determinations reveal that compounds 1-3
      are isostructural, showing a three-dimensional framework structure with (3,6)
      connected rtl topologyin whose trimers of {Cd3(COO)6} are cross-linked by Ir(ppy
      COO)33-. The structures are completely different from those of other Ir(III)
      based MOFs. Compound 1 was selected for a detailed study on sensing properties.
      The excellent luminescence as well as good water stability of 1 makes it a highly
      selective and sensitive multiresponsive luminescent sensor for Fe3+ and Cr2O72-.
      The detection limits are 67.8 and 145.1 ppb, respectively. Compound 1 can also be
      used as an optical sensor for selective sensing of adenosine triphosphate (ATP2-)
      over adenosine diphosphate (ADP2-) and adenosine monophosphate (AMP2-) in aqueous
      solution. This is the first example of iridium(III)-based MOFs for the optical
      detection of Fe3+, Cr2O72-, and ATP2-. More interestingly, the luminescent
      composite film doped with 1% (w/w) of compound 1, 1@PMMA (PMMA = poly(methyl
      methacrylate)), can be successfully prepared, which endows efficient sensitivity
      for Fe3+ and Cr2O72- detection and thus provides great potential for future
      applications.

PMID- 29363950
TI  - Developments in Glycopeptide Antibiotics.
AB  - Glycopeptide antibiotics (GPAs) are a key weapon in the fight against drug
      resistant bacteria, with vancomycin still a mainstream therapy against serious
      Gram-positive infections more than 50 years after it was first introduced. New,
      more potent semisynthetic derivatives that have entered the clinic, such as
      dalbavancin and oritavancin, have superior pharmacokinetic and target engagement
      profiles that enable successful treatment of vancomycin-resistant infections. In
      the face of resistance development, with multidrug resistant (MDR) S. pneumoniae
      and methicillin-resistant Staphylococcus aureus (MRSA) together causing 20-fold
      more infections than all MDR Gram-negative infections combined, further
      improvements are desirable to ensure the Gram-positive armamentarium is
      adequately maintained for future generations. A range of modified glycopeptides
      has been generated in the past decade via total syntheses, semisynthetic
      modifications of natural products, or biological engineering. Several of these
      have undergone extensive characterization with demonstrated in vivo efficacy,
      good PK/PD profiles, and no reported preclinical toxicity; some may be suitable
      for formal preclinical development. The natural product monobactam,
      cephalosporin, and beta-lactam antibiotics all spawned multiple generations of
      commercially and clinically successful semisynthetic derivatives. Similarly, next
      generation glycopeptides are now technically well positioned to advance to the
      clinic, if sufficient funding and market support returns to antibiotic
      development.

PMID- 29363956
TI  - Coupling between Nitrogen Fixation and Tetrachlorobiphenyl Dechlorination in a
      Rhizobium-Legume Symbiosis.
AB  - Legume-rhizobium symbioses have the potential to remediate soils contaminated
      with chlorinated organic compounds. Here, the model symbiosis between Medicago
      sativa and Sinorhizobium meliloti was used to explore the relationships between
      symbiotic nitrogen fixation and transformation of tetrachlorobiphenyl PCB 77
      within this association. 45-day-old seedlings in vermiculite were pretreated with
      5 mg L-1 PCB 77 for 5 days. In PCB-supplemented nodules, addition of the
      nitrogenase enhancer molybdate significantly stimulated dechlorination by 7.2
      fold and reduced tissue accumulation of PCB 77 (roots by 96% and nodules by 93%).
      Conversely, dechlorination decreased in plants exposed to a nitrogenase inhibitor
      (nitrate) or harboring nitrogenase-deficient symbionts (nifA mutant) by 29% and
      72%, respectively. A range of dechlorinated products (biphenyl, methylbiphenyls,
      hydroxylbiphenyls, and trichlorobiphenyl derivatives) were detected within
      nodules and roots under nitrogen-fixing conditions. Levels of nitrogenase-derived
      hydrogen and leghemoglobin expression correlated positively with nodular
      dechlorination rates, suggesting a more reducing environment promotes PCB
      dechlorination. Our findings demonstrate for the first time that symbiotic
      nitrogen fixation acts as a driving force for tetrachlorobiphenyl dechlorination.
      In turn, this opens new possibilities for using rhizobia to enhance
      phytoremediation of halogenated organic compounds.

PMID- 29363955
TI  - Synthesis of Stachyobifiose Using Bifidobacterial alpha-Galactosidase Purified
      from Recombinant Escherichia coli.
AB  - The prebiotic effects of GOS (galactooligosaccharides) are known to depend on the
      glycosidic linkages, degree of polymerization (DP), and the monosaccharide
      composition. In this study, a novel form of alpha-GOS with a potentially improved
      prebiotic effect was synthesized using bifidobacterial alpha-galactosidase (alpha
      Gal) purified from recombinant Escherichia coli. The carbohydrate produced was
      identified as alpha-d-galactopyranosyl-(1->6)-O-alpha-d-glucopyranosyl-(1->2)
      [alpha-d-galactopyranosyl-(1->6)-O-beta-d-fructofuranoside] and was termed
      stachyobifiose. Among 17 nonprobiotics, 16 nonprobiotics showed lower growth on
      stachyobifiose than beta-GOS. In contrast, among the 16 probiotics, 6 probiotics
      showed higher growth on stachyobifiose than beta-GOS. When compared with
      raffinose, stachyobifiose was used less by nonprobiotics than raffinose.
      Moreover, compared with stachyose, stachyobifiose was used less by Escherichia
      coli, Enterobacter cloacae, and Clostridium butyricum. The average amounts of
      total short-chain fatty acids (SCFA) produced were in the order of stachyobifiose
      > stachyose > raffinose > beta-GOS. Taken together, stachyobifiose is expected to
      contribute to beneficial changes of gut microbiota.

PMID- 29363958
TI  - You Say You Want Some Resolutions?

PMID- 29363957
TI  - Integrative CO2 Capture and Hydrogenation to Methanol with Reusable Catalyst and
      Amine: Toward a Carbon Neutral Methanol Economy.
AB  - Herein we report an efficient and recyclable system for tandem CO2 capture and
      hydrogenation to methanol. After capture in an aqueous amine solution, CO2 is
      hydrogenated in high yield to CH3OH (>90%) in a biphasic 2-MTHF/water system,
      which also allows for easy separation and recycling of the amine and catalyst for
      multiple reaction cycles. Between cycles, the produced methanol can be
      conveniently removed in vacuo. Employing this strategy, catalyst Ru-MACHO-BH and
      polyamine PEHA were recycled three times with 87% of the methanol producibility
      of the first cycle retained, along with 95% of catalyst activity after four
      cycles. CO2 from dilute sources such as air can also be converted to CH3OH using
      this route. We postulate that the CO2 capture and hydrogenation to methanol
      system presented here could be an important step toward the implementation of the
      carbon neutral methanol economy concept.

PMID- 29363959
TI  - Electrochemistry and Spectroelectrochemistry of Cobalt Porphyrins with pi
      Extending and/or Highly Electron-Withdrawing Pyrrole Substituents. In Situ
      Electrogeneration of sigma-Bonded Complexes.
AB  - A series of cobalt porphyrins with pi-extending or highly electron-withdrawing
      beta-pyrrole substituents were investigated as to their electrochemistry,
      spectroscopic properties, and reactivity after electroreduction or
      electroxidation in nonaqueous media. Each porphyrin, represented as PorCo (where
      Por = TPP(NO2)Y2 or TPP(NO2)Y6 and Y = phenyl, phenylethynyl, Br, or CN) was
      shown to undergo multiple redox reactions involving the conjugated pi-ring system
      or central metal ion which could exist in a Co(III), Co(II), or Co(I) oxidation
      state under the application of an applied oxidizing or reducing potential.
      Thermodynamic half-wave potentials for the stepwise conversion between each
      oxidation state of [PorCo]n (where n ranged from +3 to -3) were measured by
      cyclic voltammetry and analyzed as a function of the compound structure and
      properties of the electrochemical solvent. UV-visible spectra were obtained for
      each oxidized or reduced porphyrin in up to six different oxidation states
      ranging from [PorCo]3- to [PorCo]3+ and analyzed as a function of the compound
      structure and utilized electrochemical solvent. Chemically or electrochemically
      generated Co(I) porphyrins are known to be highly reactive in solutions
      containing alkyl or aryl halides, and this property was utilized to in situ
      generate a new series of methyl carbon-bonded cobalt(III) porphyrins with the
      same pi-extending or highly electron-withdrawing substituents as the initial
      Co(II) derivatives. The electrosynthesized carbon-bonded Co(III) porphyrins were
      then characterized as to their own electrochemical and spectroscopic properties
      after the addition of one, two, or three electrons in nonaqueous media.

PMID- 29363960
TI  - Generation and Confinement of Long-Lived N-Oxyl Radical and Its Photocatalysis.
AB  - Generation of controllable carbon radical under the assistance of N-oxyl radical
      is an efficient method for the activation of C-H bonds in hydrocarbons. We herein
      report that irradiation of alpha-Fe2O3 and N-hydroxyphthalimide (NHPI) under 455
      nm light generates phthalimide-N-oxyl radical (PINO*), which after being formed
      by oxidation with holes, is confined on alpha-Fe2O3 surface. The half-life time
      of the confined radical reaches 22 s as measured by in situ electron paramagnetic
      resonance (EPR) after the light being turned off. This allows the long-lived N
      oxyl radical to abstract the H from C-H bond to form a carbon radical that reacts
      with molecular oxygen to form R3C-OO. species, decomposition of which leads to
      oxygenated products.

PMID- 29363961
TI  - General Strategy for Rapid Production of Low-Dimensional All-Inorganic CsPbBr3
      Perovskite Nanocrystals with Controlled Dimensionalities and Sizes.
AB  - Currently, all-inorganic CsPbX3 (X = Br, I, Cl) perovskite nanocrystals (NCs) are
      shining stars with exciting potential applications in optoelectronic devices such
      as solar cells, light-emitting diodes, lasers, and photodetectors, due to their
      superior performance in comparison to their organic-inorganic hybrid
      counterparts. In the present work, we report a general strategy based on a
      microwave technique for the rapid production of low-dimensional all-inorganic
      CsPbBr3 perovskite NCs with tunable morphologies within minutes. The effect of
      the key parameters such as the introduced ligands, solvents, and PbBr2 precursors
      and microwave powers as well as the irradiation times on the production of
      perovskite NCs was systematically investigated, which allowed their growth with
      tunable dimensionalities and sizes. As a proof of concept, the ratio of OA to OAm
      as well as the concentration of PbBr2 precursor played important roles in
      triggering the anisotropic growth of the perovskite NCs, favoring their growth
      into 1D/2D single-crystalline nanostructures. Meanwhile, their sizes could be
      tailored by controlling the microwave powers and irradiation times. The mechanism
      for the tunable growth of perovskite NCs is discussed.

PMID- 29363962
TI  - Alcohol Solvent Effects in the Synthesis of Co3O4 Metal-Oxide Nanoparticles:
      Disproof of a Surface-Ligand Thermodynamic Effect en Route to Alternative Kinetic
      and Thermodynamic Explanations.
AB  - The synthesis of Co3O4 core nanoparticles from cobalt acetate is explored in
      alcohol solvents plus limited water using O2 as oxidant and NH4OH as the base,
      all in comparison to controls in water alone employing the otherwise identical
      synthetic procedure. Syntheses in EtOH or t-BuOH cosolvents with limited water
      yield phase-pure and size-controlled (3 +/- 1 nm) Co3O4-core nanoparticles. In
      marked contrast, the synthesis in water alone yields mixed phases of Co3O4 and
      beta-Co(OH)2 with a very large particle-size range (14-400 nm). Importantly,
      acidic reductive digestion of the Co3O4 particles followed by 1H NMR on the
      resultant solution yields no detectable EtOH in nanoparticles prepared in EtOH,
      nor any detectable t-BuOH in nanoparticles prepared in t-BuOH (~5% detection
      limits for each alcohol), despite the dramatic effect of each alcohol cosolvent
      on the resultant cobalt-oxide product. Instead, in both cases HOAc is detected
      and quantified, indicative of OAc- as a surface ligand-and not EtO- or t-BuO- as
      the surface ligand. The resultant ROH cosolvent-derived particles were
      characterized by powder X-ray diffraction, Fourier transform infrared
      spectroscopy, high-resolution transmission electron microscopy, plus elemental
      analysis to arrive at an approximate, average molecular formula in the case of
      the particles prepared in EtOH, {[Co3O4(C2H3O2)]-[(NH4+)0.3(H+0.7)]+.(H2O)}~216.
      The key finding is that, because EtOH and t-BuOH have a substantial effect on the
      phase- and size-dispersion of the cobalt-oxide nanoparticle product, yet the
      intact alcohol does not show up in the final Co3O4 nanoparticle product, the
      effect of these alcohols cannot be a surface-ligand thermodynamic effect on the
      net nanoparticle formation reaction. A careful search of the literature provided
      scattered, but consistent, literature in which anions or other additives have
      large effects on metal-oxide nanoparticle formation reactions, yet also do not
      show up in the nanoparticle products-that is, where the observed effects are
      again not due to binding by that anion or other additive in a surface-ligand
      thermodynamic effect on the overall reaction. Alternative hypotheses are provided
      as to the origin of ROH solvent effects on metal-oxide nanoparticles.

PMID- 29363963
TI  - Superconductivity in Perovskite Ba1-xLnx(Bi0.20Pb0.80)O3-delta (Ln = La, Ce, Pr,
      Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu).
AB  - Solid solutions Ba1-xLnx(Bi0.20Pb0.80)O3-delta (Ln = La, Ce, Pr, Nd, Sm, Eu, Gd,
      Tb, Dy, Ho, Er, Tm, Yb, Lu; 0.00 <= x ? 0.15) have been prepared under 850 
      degrees C. They all crystallize in space group P1 at room temperature. XPS data
      indicate that the valences are 5+ and 3+ for bismuth, 4+ and 2+ for lead, and 3+
      or 4+ for lanthanide. Some of them are superconductors. The superconductive
      transition temperature Tczero decreases or remains constant with an increase of
      Ln in the sample when Ln = La, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu.
      However, Tczero first decreases, then increases, and finally decreases when Ln =
      Ce, Pr, which is due to the corresponding sample changes from hole-doped to
      electron-doped superconductors with an increase of Ce or Pr in the sample.

PMID- 29363964
TI  - Redox Potentials for Tetraplatin, Satraplatin, Its Derivatives, and Ascorbic
      Acid: A Computational Study.
AB  - Redox potentials of the Pt(IV) complexes, such as satraplatin, tetraplatin, and
      several others, are determined at the density functional theory (DFT) level (with
      B3LYP, omega-B97XD, PBE1PBE, TPSSTPSS, M06-L, M11-L, and MN12-L functionals) and
      compared with post-Hartree-Fock methods MP2 and CCSD(T). Calculations are
      performed in water solution employing an implicit solvation model. The impact of
      replacement of a chloro ligand by a water molecule (hydration in the equatorial
      plane of the complexes) is also explored. Furthermore, an influence of solvent pH
      on the magnitude of the redox potentials is discussed for such hydrated
      complexes. The obtained results are compared with available experimental data
      leading to a root-mean-square deviation (RMSD) of ca. 0.23 V, using the CCSD(T)/6
      31+G(d)/IEF-PCM/scaled-UAKS level. Distribution of the electron density is
      analyzed at the B3LYP/6-311++G(2df,2pd) level. Also, a correlation between
      binding energies of axial ligands and the redox potential is demonstrated. Since
      the Pt(IV) complexes are considered in the framework of anticancer treatment,
      possible reducing agents in bioenvironment are searched. From this reason, the
      reduction potential of different protonation states of ascorbic acid is also
      presented.

PMID- 29363965
TI  - Catalytic Asymmetric Dearomative [3 + 2] Cycloaddition of Electron-Deficient
      Indoles with All-Carbon 1,3-Dipoles.
AB  - The first catalytic asymmetric dearomative [3 + 2] cycloaddition of 3
      nitroindoles with vinylcyclopropanes has been established, which constructed
      chiral cyclopenta[b]indoline scaffolds in generally high enantioselectivities (up
      to 97% ee). This reaction also represents the first application of all-carbon 1,3
      dipoles in catalytic asymmetric dearomative [3 + 2] cycloadditions of 3
      nitroindoles. This approach will not only advance the catalytic asymmetric
      dearomatization reactions of electron-deficient indoles but also provide an
      efficient method for constructing chiral cyclopenta[b]indoline scaffolds.

PMID- 29363967
TI  - Novel Phosphodiesterase Inhibitors for Cognitive Improvement in Alzheimer's
      Disease.
AB  - Alzheimer's disease (AD) is one of the greatest public health challenges.
      Phosphodiesterases (PDEs) are a superenzyme family responsible for the hydrolysis
      of two second messengers: cyclic adenosine monophosphate (cAMP) and cyclic
      guanosine monophosphate (cGMP). Since several PDE subfamilies are highly
      expressed in the human brain, the inhibition of PDEs is involved in
      neurodegenerative processes by regulating the concentration of cAMP and/or cGMP.
      Currently, PDEs are considered as promising targets for the treatment of AD since
      many PDE inhibitors have exhibited remarkable cognitive improvement effects in
      preclinical studies and over 15 of them have been subjected to clinical trials.
      The aim of this review is to summarize the outstanding progress that has been
      made by PDE inhibitors as anti-AD agents with encouraging results in preclinical
      studies and clinical trials. The binding affinity, pharmacokinetics, underlying
      mechanisms, and limitations of these PDE inhibitors in the treatment of AD are
      also reviewed and discussed.

PMID- 29363966
TI  - Arabinoxylo-Oligosaccharides and Inulin Impact Inter-Individual Variation on
      Microbial Metabolism and Composition, Which Immunomodulates Human Cells.
AB  - Fecal batch fermentations coupled to cocultures of epithelial cells and
      macrophages were used to compare how arabinoxylo-oligosaccharides (AXOS) and
      inulin modulate gut microbial activity and composition of three different human
      donors and subsequently the epithelial permeability and immune response. Both
      inulin and AXOS decreased the pH during incubation (-1.5 pH units), leading to
      increased productions of acetate, propionate, and butyrate. Differences in terms
      of metabolites production could be linked to specific microbial alterations at
      genus level upon inulin/AXOS supplementation (i.e., Bifidobacterium, Bacteroides,
      Prevotella and unclassified Erysipelotrichaceae), as shown by 16S-targeted
      Illumina sequencing. Both products stimulated gut barrier and immune function
      with increases in TEER, NF-KB, IL-10, and IL-6. Ingredients with different
      structures selectively modulate the microbiota of a specific donor leading to
      differential changes at metabolic level. The extent of this effect is donor
      specific and is linked to a final specific modulation of the host's immune
      system.

PMID- 29363968
TI  - Partial Photochemical Oxidation Was a Dominant Fate of Deepwater Horizon Surface
      Oil.
AB  - Following the Deepwater Horizon (DWH) blowout in 2010, oil floated on the Gulf of
      Mexico for over 100 days. In the aftermath of the blowout, substantial
      accumulation of partially oxidized surface oil was reported, but the pathways
      that formed these oxidized residues are poorly constrained. Here we provide five
      quantitative lines of evidence demonstrating that oxidation by sunlight largely
      accounts for the partially oxidized surface oil. First, residence time on the
      sunlit sea surface, where photochemical reactions occur, was the strongest
      predictor of partial oxidation. Second, two-thirds of the partial oxidation from
      2010 to 2016 occurred in less than 10 days on the sunlit sea surface, prior to
      coastal deposition. Third, multiple diagnostic biodegradation indices, including
      octadecane to phytane, suggest that partial oxidation of oil on the sunlit sea
      surface was largely driven by an abiotic process. Fourth, in the laboratory, the
      dominant photochemical oxidation pathway of DWH oil was partial oxidation to
      oxygenated residues rather than complete oxidation to CO2. Fifth, estimates of
      partial photo-oxidation calculated with photochemical rate modeling overlap with
      observed oxidation. We suggest that photo-oxidation of surface oil has
      fundamental implications for the response approach, damage assessment, and
      ecosystem restoration in the aftermath of an oil spill, and that oil fate models
      for the DWH spill should be modified to accurately reflect the role of sunlight.

PMID- 29363969
TI  - Total Synthesis of Pyrophen and Campyrones A-C.
AB  - The first total syntheses of the natural products pyrophen and campyrones A-C,
      isolated from the fungus Aspergillus niger, have been achieved in six steps
      starting from commercially available N-Boc amino acids. Key steps in this
      sequence include a vinylogous Claisen condensation to achieve fragment coupling
      and a dioxinone thermolysis/cyclization cascade to form the alpha-pyrone ring.
      The route described herein afforded the natural products in 15-25% overall yield,
      furnishing sufficient material for testing in biological assays.

PMID- 29363970
TI  - Choose Your Poison-Space-Use Strategy Influences Pollutant Exposure in Barents
      Sea Polar Bears.
AB  - Variation in space-use is common within mammal populations. In polar bears, Ursus
      maritimus, some individuals follow the sea ice (offshore bears) whereas others
      remain nearshore yearlong (coastal bears). We studied pollutant exposure in
      relation to space-use patterns (offshore vs coastal) in adult female polar bears
      from the Barents Sea equipped with satellite collars (2000-2014, n = 152). First,
      we examined the differences in home range (HR) size and position, body condition,
      and diet proxies (nitrogen and carbon stable isotopes, n = 116) between offshore
      and coastal space-use. Second, we investigated how HR, space-use, body condition,
      and diet were related to plasma concentrations of polychlorinated biphenyls
      (PCBs), organochlorine pesticides (OCPs) ( n = 113), perfluoroalkyl substances
      (PFASs; n = 92), and hydroxylated-PCBs ( n = 109). Offshore females were in
      better condition and had a more specialized diet than did coastal females. PCBs,
      OCPs, and hydroxylated-PCB concentrations were not related to space-use strategy,
      yet PCB concentrations increased with increasing latitude, and hydroxylated-PCB
      concentrations were positively related to HR size. PFAS concentrations were 30
      35% higher in offshore bears compared to coastal bears and also increased
      eastward. On the basis of the results we conclude that space-use of Barents Sea
      female polar bears influences their pollutant exposure, in particular plasma
      concentrations of PFAS.

PMID- 29363971
TI  - Design and Syntheses of Highly Potent Teixobactin Analogues against
      Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), and
      Vancomycin-Resistant Enterococci (VRE) in Vitro and in Vivo.
AB  - The cyclic depsipeptide, teixobactin, kills a number of Gram-positive bacteria,
      including methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium
      tuberculosis without detectable resistance. To date, teixobactin is the only
      molecule in its class that has shown in vivo antibacterial efficacy. In this
      work, we designed and synthesized 10 new in vivo ready teixobactin analogues.
      These analogues showed highly potent antibacterial activities against
      Staphylococcus aureus, MRSA, and vancomycin-resistant enterococci (VRE) in vitro.
      One analogue, d-Arg4-Leu10-teixobactin, 2, was found to be noncytotoxic in vitro
      and in vivo. Moreover, topical instillation of peptide 2 in a mouse model of S.
      aureus keratitis decreased the bacterial bioburden (>99.0% reduction) and corneal
      edema significantly as compared to untreated mouse corneas. Collectively, our
      results have established the high therapeutic potential of a teixobactin analogue
      in attenuating bacterial infections and associated severities in vivo.

PMID- 29363972
TI  - Dynamic Fingering in Adhered Lipid Membranes.
AB  - Artificial lipid membranes incorporating proteins have frequently been used as
      models for the dynamic organization of biological structures in living cells as
      well as in the development of biology-inspired technologies. We report here on
      the experimental demonstration and characterization of a pattern-forming process
      that occurs in a lipid bilayer membrane adhered via biotin-avidin binding to a
      second lipid membrane that is supported by a solid substrate. Adhesion regions
      are roughly circular with a diameter of about 25 MUm. Using confocal fluorescence
      microscopy, we record time series of dynamic fingering patterns that grow in the
      upper lipid membrane and intermembrane biotin-avidin bonds. The fingers are
      micrometer-scale elongated pores that grow from the edge of an already-stabilized
      hole. Finger growth is saltatory on the scale of tens of seconds. We find that as
      the fingers grow and the density of adhesion proteins increases, the rate of
      finger growth decreases exponentially and the width of newly formed fingers
      decreases linearly. We show that these findings are consistent with a
      thermodynamic description of dynamic pore formation and stabilization.

PMID- 29363973
TI  - Synthesis of 4-Difluoromethylquinolines by NHC-Catalyzed Umpolung of Imines.
AB  - The N-heterocyclic carbene (NHC)-catalyzed umpolung of aldimines for the
      synthesis of 4-difluoromethylquinoline derivatives is reported. In the presence
      of NHCs, the intramolecular cyclization of aldimines bearing a moderately
      electron-poor double bond due to the presence of the -CF3 group likely proceeds
      via the intermediacy of the aza-Breslow intermediate. The key to the success of
      this aza-Stetter type transformation is the NHC generated from the bicyclic
      triazolium salt using DBU as the base.

PMID- 29363974
TI  - Construction of C(sp2)-X (X = Br, Cl) Bonds through a Copper-Catalyzed Atom
      Transfer Radical Process: Application for the 1,4-Difunctionalization of
      Isoquinolinium Salts.
AB  - A highly efficient Cu-catalyzed 1,4-difunctionalization of isoquinolinium salts
      was developed with ether and X- (X = Br, Cl) as the halogen source under mild
      conditions. This transformation involves the combination of oxidative coupling
      and copper-catalyzed halogen atom-transfer radical processes. This method not
      only provides an efficient way to prepare various substituted azaarenes but also
      achieves the selective construction of C(sp2)-X (X = Br, Cl) bonds from a halogen
      anion and nucleophilic carbon atom via a free-radical process.

PMID- 29363975
TI  - Pulmonary Delivery of Ceftazidime for the Treatment of Melioidosis in a Murine
      Model.
AB  - Burkholderia pseudomallei, the etiological agent responsible for melioidosis,
      exhibits a great public health toll in its endemic regions. The elevation of B.
      pseudomallei to a Tier I select agent underscores the urgent need for effective
      therapeutics and preventatives. The current treatment regimen for melioidosis is
      suboptimal, requiring an intensive phase of intravenous antibiotic followed by
      months of oral antibiotics. Inhaled antibiotics are a promising avenue to pursue
      for pulmonary diseases, including melioidosis, since this mode of delivery mimics
      the likely exposure route and can provide high drug doses directly to the
      infected tissue. Ceftazidime was delivered via a nose-only system to BALB/c mice
      challenged with B. pseudomallei. Mice treated with nebulized ceftazidime became
      symptomatic but survived until study end, which was comparable to those treated
      intraperitoneally. Upon necropsy, bacteria remained within the spleens of the
      majority of the experimental animals. The effectiveness of nebulized ceftazidime
      warrants additional studies to improve the treatment regimen and to test as a
      prophylactic therapy against B. pseudomallei.

PMID- 29363976
TI  - Correction to Synthetic Study on Pactamycin: Stereoselective Synthesis of the
      Cyclopentane Core Framework.

PMID- 29363977
TI  - Enantioselective Organocatalytic 1,6-Addition of Azlactones to para-Quinone
      Methides: An Access to alpha,alpha-Disubstituted and beta,beta-Diaryl-alpha-amino
      acid Esters.
AB  - This work describes the first enantioselective 1,6-additions of azlactones to
      para-quinone methides. In the presence of a chiral phosphoric acid, 1,6-adducts
      were obtained in high yields (up to 96%) with excellent diastereoselectivities
      and enantioselectivities (all >20:1 diastereoselectivity ratio (dr), up to 99%
      enantiomeric excess (ee)). Importantly, the method offers a facile synthetic
      approach, not only to enantiopure alpha,alpha-disubstituted alpha-amino acid
      esters, but also to unnatural enantioenriched beta,beta-diaryl-alpha-amino acid
      esters bearing adjacent tertiary and quaternary stereogenic centers.

PMID- 29363978
TI  - UGT74AN1, a Permissive Glycosyltransferase from Asclepias curassavica for the
      Regiospecific Steroid 3-O-Glycosylation.
AB  - A permissive steroid glycosyltransferase (UGT74AN1) from Asclepias curassavica
      exhibited robust capabilities for the regiospecific C3 glycosylation of
      cardiotonic steroids and C21 steroid precursors, and unprecedented promiscuity
      toward 53 structurally diverse natural and unnatural compounds to form O-, N-,
      and S-glycosides, along with the catalytic reversibility for a one-pot
      transglycosylation reaction. These findings highlight UGT74AN1 as the first
      regiospecific catalyst for cardiotonic steroid C3 glycosylation and exhibit
      significant potential for glycosylation of diverse bioactive molecules in drug
      discovery.

PMID- 29363980
TI  - Chemoselective Synthesis of Structurally Diverse 3,4-Dihydroquinazoline-2(1H)
      thiones and 4H-Benzo[d][1,3]thiazines.
AB  - An efficient, mild, and substrate/catalyst-controlled chemoselective reaction of
      o-isothiocyanato-(E)-cinnamaldehyde with amines has been established, producing
      three types of six-membered heterocycles: 2-(4H-benzo[d][1,3]thiazin-4
      yl)acetaldehydes, 2-(2-thioxo-1,2,3,4-tetrahydroquinazolin-4-yl)acetaldehydes,
      and (E)-4-(2-methoxyvinyl)-4H-benzo[d][1,3]thiazines. The reaction scopes were
      quite broad and excellent yield was achieved. This method is extremely efficient
      and practical and can be conducted on a gram-scale with slightly inferior
      reactivity under catalyst-free conditions at low cost, making it an ideal
      alternative to existing methods.

PMID- 29363979
TI  - Dynamic Control of Particle Deposition in Evaporating Droplets by an External
      Point Source of Vapor.
AB  - The deposition of particles on a surface by an evaporating sessile droplet is
      important for phenomena as diverse as printing, thin-film deposition, and self
      assembly. The shape of the final deposit depends on the flows within the droplet
      during evaporation. These flows are typically determined at the onset of the
      process by the intrinsic physical, chemical, and geometrical properties of the
      droplet and its environment. Here, we demonstrate deterministic emergence and
      real-time control of Marangoni flows within the evaporating droplet by an
      external point source of vapor. By varying the source location, we can modulate
      these flows in space and time to pattern colloids on surfaces in a controllable
      manner.

PMID- 29363981
TI  - Bioinspired Synthesis of Juglorubin from Juglomycin C.
AB  - In this paper, the synthesis of juglorubin, a natural red dye, from juglomycin C,
      a plausible biogenetic precursor, is reported. Sequential intermolecular and
      intramolecular Michael additions of juglomycin C, oxidation, and skeletal
      transformation proceeded in phosphate buffer to afford an undehydrated derivative
      of juglorubin. Subsequent dehydration of the secondary alcohol afforded
      juglorubin. The one-pot synthesis of juglorubin from juglomycin C was also
      achieved. The photophysical properties of synthetic juglorubin and its
      derivatives were evaluated.

PMID- 29363982
TI  - Exciton Localization on Ru-Based Photosensitizers Induced by Binding to Lipid
      Membranes.
AB  - The characterization of electronic properties of metal complexes embedded in
      membrane environments is of paramount importance to develop efficient
      photosensitizers in optogenetic applications. Molecular dynamics and QM/MM
      simulations together with quantitative wave function analysis reveal a
      directional electronic redistribution of the exciton formed upon excitation of
      [Ru(bpy)2(bpy-C17)]2+ when going from water to a lipid bilayer, despite the fact
      that the media influence neither the metal-to-ligand charge-transfer character
      nor the excitation energy of the absorption spectra. When the photosensitizer is
      embedded into the DOPC lipid membrane, exciton population is mainly located in
      the bypyridyl sites proximal to the positively charged surface of the bilayer due
      to electrostatic interactions. This behavior shows that the electronic structure
      of metal complexes can be controlled through the binding to external species,
      underscoring the crucial role of the environment in directing the electronic flow
      upon excitation and thus helping rational tuning of optogenetic agents.

PMID- 29363983
TI  - Redox-Neutral alpha-C-H Functionalization of Pyrrolidin-3-ol.
AB  - A redox-neutral alpha-C-H oxygenation of commercially available pyrrolidin-3-ol
      with a monoprotected p-quinone generated an N-aryliminium ion intermediate, which
      reacted in situ with boronic acid nucleophiles to produce a series of cis-2
      substituted pyrrolidin-3-ols. With this strategy, 8-epi-(-)-lentiginosine was
      synthesized from (3R,4R)-pyrrolidine-3,4-diol in three steps.

PMID- 29363984
TI  - Iridium-Catalyzed Highly Enantioselective Transfer Hydrogenation of Aryl N
      Heteroaryl Ketones with N-Oxide as a Removable ortho-Substituent.
AB  - A highly enantioselective transfer hydrogenation of non-ortho-substituted aryl N
      heteroaryl ketones, using readily available chiral diamine-derived iridium
      complex (S,S)-1f as a catalyst and sodium formate as a hydrogen source in a
      mixture of H2O/i-PrOH (v/v = 1:1) under ambient conditions, is described. The
      chiral aryl N-heteroaryl methanols were obtained with up to 98.2% ee by
      introducing an N-oxide as a removable ortho-substituent. In contrast, no more
      than 15.1% ee was observed in the absence of an N-oxide moiety. Furthermore, the
      practical utility of this protocol was also demonstrated by gram-scale asymmetric
      synthesis of bepotastine besilate in 51% total yield and 99.9% ee.

PMID- 29363985
TI  - Pulmonary hypertension and exercise training: a synopsis on the more recent
      evidences.
AB  - The benefits of exercise training in virtually all humans, including those with a
      clinically stable chronic disease are numerous. The potential value lies in the
      fact that functional capacity is oftentimes significantly compromised. Exercise
      training not only play a role in reversing some of the pathophysiologic processes
      associated with chronic diseases but also improves clinical trajectory. Given the
      significant pathologic consequences associated with pulmonary hypertension and
      its implications for deteriorating right ventricular function as well as the
      perceived potential for a precipitous and possibly critical drop in cardiac
      output during periods of physical exertion, exercise training was historically
      not recommended for these patients. More recently, a promising body of literature
      demonstrating the safety and efficacy of exercise training (with benefit on
      exercise capacity, peak oxygen consumption and quality of life) in pulmonary
      hypertension patients has emerged, but the conclusion about the effects of
      exercise training were non-exhaustive and therefore there is still a lack of
      knowledge regarding exercise training for these patients. Thus, we aim to
      ascertain the current effectiveness of exercise rehabilitation for pulmonary
      hypertension by performing a brief overview on the latest currently available
      evidences in such an "at a glance" synopsis addressed to summarize/quantify the
      more recent existing body of literature. KEY MESSAGES Exercise training was
      historically not recommended in pulmonary hypertension. Recently, exercise
      training safety-efficacy in pulmonary hypertension has emerged. Exercise training
      should be recommended in addition to optimal medical therapy.

PMID- 29363986
TI  - Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S.
      Children and Adolescents, 2016.
AB  - The purpose of this study is to estimate the national prevalence of parent
      reported attention deficit/hyperactivity disorder (ADHD) diagnosis and treatment
      among U.S. children 2-17 years of age using the 2016 National Survey of
      Children's Health (NSCH). The NSCH is a nationally representative, cross
      sectional survey of parents regarding their children's health that underwent a
      redesign before the 2016 data collection. It included indicators of lifetime
      receipt of an ADHD diagnosis by a health care provider, whether the child
      currently had ADHD, and receipt of medication and behavioral treatment for ADHD.
      Weighted prevalence estimates were calculated overall and by demographic and
      clinical subgroups (n = 45,736). In 2016, an estimated 6.1 million U.S. children
      2-17 years of age (9.4%) had ever received an ADHD diagnosis. Of these, 5.4
      million currently had ADHD, which was 89.4% of children ever diagnosed with ADHD
      and 8.4% of all U.S. children 2-17 years of age. Of children with current ADHD,
      almost two thirds (62.0%) were taking medication and slightly less than half
      (46.7%) had received behavioral treatment for ADHD in the past year; nearly one
      fourth (23.0%) had received neither treatment. Similar to estimates from previous
      surveys, there is a large population of U.S. children and adolescents who have
      been diagnosed with ADHD by a health care provider. Many, but not all, of these
      children received treatment that appears to be consistent with professional
      guidelines, though the survey questions are limited in detail about specific
      treatment types received. The redesigned NSCH can be used to annually monitor
      diagnosis and treatment patterns for this highly prevalent and high-impact
      neurodevelopmental disorder.

PMID- 29363987
TI  - Association of possible sleep bruxism in children with different chronotype
      profiles and sleep characteristics.
AB  - Sleep bruxism (SB) in children has been associated with several sleep
      characteristics, which may alter their sleep pattern. This change affects the
      internal biological clock and consequently the chronotype profile. The aim of
      this study was to evaluate the existence of an association between possible SB in
      children with specific chronotype profiles and sleep characteristics. The study
      included 207 parents/guardians of children aged between 3 and 12 years who were
      waiting for their children's dental treatment at the Pediatric Dentistry Clinic
      of the Federal University of Rio de Janeiro, Brazil. A questionnaire on the socio
      demographic characteristics of parents and children as well as on the features of
      the children's sleep was applied. In addition, the CIRENS scale (Circadian Energy
      Scale) was completed by the parents to identify the children's chronotype. A chi
      squared test was used to determine the association between possible SB, the
      chronotype, and sleep characteristics. A multiple logistic regression model was
      implemented to observe the influence of chronotype, age, and other independent
      variables on the possible SB. The logistic regression model demonstrated that
      nocturnal agitation (p = 0.009; OR = 3.42) and nightmares (p = 0.045; OR = 3.24)
      were associated with possible SB in children. Although no significant association
      (p = 0 .089) between the chronotype profile and possible SB was observed in the 3
      to 5 years age group, a proportional difference was observed between the
      chronotype categories in this age group-12.5% of children with SB had a morning
      type, while 26.4% had an intermediate type and 47.8% an evening type compared to
      those without possible SB. Nocturnal agitation and nightmares were associated
      with possible SB. In addition, young children with an evening chronotype had a
      tendency toward possible SB.

PMID- 29363988
TI  - Effects of 12-week brisk walking training on exercise blood pressure in elderly
      patients with essential hypertension: a pilot study.
AB  - BACKGROUND: Essential hypertension (EP) is characterized by blood pressure (BP)
      elevations, which often lead to target organ damage and cardiovascular illness.
      The following study investigates whether aerobic exercise programs with different
      intensities could reduce the magnitude of BP rise. METHODS: Patients with
      essential hypertension were recruited from the Baoshan Community Health Service
      Center. A total of 46 patients were finally selected and randomly assigned into
      two groups: control group (CON) included patients who did not participate in
      exercise intervention training; treatment group (TRG) included patients who
      participated in 12-week brisk walking training (60-min of brisk walking, three
      times a week for a total of 12 weeks). 3-minute step tests of low and high
      intensity were conducted pre- and post-intervention. To compare the effects of
      exercise intervention, 23 subjects with normal blood pressure (NBP) who did not
      participate in 12-week brisk walking training, were recruited. RESULTS: After 12
      weeks of brisk walking, SBP of TRG during resting, low and high-intensity
      exercise was significantly reduced by 8.3mmHg, 15.6mmHg, and 22.6mmHg,
      respectively; while HR of TRG's during resting, low and high intensity was
      significantly reduced by 3.6beats/minute, 8.7beats/minute and 11.3beats/minute,
      respectively. Meanwhile, after 12 weeks of brisk walking, TRG's steps per day,
      [Formula: see text]o2max, moderate physical activity time and physical activity
      energy expenditure significantly increased by 6000 steps, 2.4 ml/kg/m, 40 minutes
      and 113 kcal, respectively. At the same time, TRG's body fat rate and sedentary
      time significantly reduced by 2% and 60 minutes per day. CONCLUSION: Brisk
      walking can reduce the magnitude of BP rise during exercise of different
      intensities and may be reduced the risk of acute cardiovascular incidents in
      elderly patients with essential hypertension. ABBREVIATIONS: EP: Essential
      hypertension; BP: blood pressure; CON: control group; TRG: treatment group; NBP:
      normal blood pressure; PA: physical activity.

PMID- 29363989
TI  - The effect of history of severe mental illness on mortality in colorectal cancer
      cases: a register-based cohort study.
AB  - BACKGROUND: While the link between mental illness and cancer survival is well
      established, few studies have focused on colorectal cancer. We examined outcomes
      of colorectal cancer among persons with a history of severe mental illness (SMI).
      MATERIAL AND METHODS: We identified patients with their first colorectal cancer
      diagnosis in 1990-2013 (n = 41,708) from the Finnish Cancer Registry, hospital
      admissions due to SMI preceding cancer diagnosis (n = 2382) from the Hospital
      Discharge Register and deaths from the Causes of Death statistics. Cox regression
      models were used to study the impact on SMI to mortality differences. RESULTS: We
      found excess colorectal cancer mortality among persons with a history of
      psychosis and with substance use disorder. When controlling for age, comorbidity,
      stage at presentation and treatment, excess mortality risk among men with a
      history of psychosis was 1.72 (1.46-2.04) and women 1.37 (1.20-1.57). Among men
      with substance use disorder, the excess risk was 1.22 (1.09-1.37). CONCLUSION:
      Understanding factors contributing to excess mortality among persons with a
      history of psychosis or substance use requires more detailed clinical studies and
      studies of care processes among these vulnerable patient groups. Collaboration
      between patients, mental health care and oncological teams is needed to improve
      outcomes of care.

PMID- 29363991
TI  - Recent applications of multivariate data analysis methods in the authentication
      of rice and the most analyzed parameters: A review.
AB  - Rice is one of the most important staple foods around the world. Authentication
      of rice is one of the most addressed concerns in the present literature, which
      includes recognition of its geographical origin and variety, certification of
      organic rice and many other issues. Good results have been achieved by
      multivariate data analysis and data mining techniques when combined with specific
      parameters for ascertaining authenticity and many other useful characteristics of
      rice, such as quality, yield and others. This paper brings a review of the recent
      research projects on discrimination and authentication of rice using multivariate
      data analysis and data mining techniques. We found that data obtained from image
      processing, molecular and atomic spectroscopy, elemental fingerprinting, genetic
      markers, molecular content and others are promising sources of information
      regarding geographical origin, variety and other aspects of rice, being widely
      used combined with multivariate data analysis techniques. Principal component
      analysis and linear discriminant analysis are the preferred methods, but several
      other data classification techniques such as support vector machines, artificial
      neural networks and others are also frequently present in some studies and show
      high performance for discrimination of rice.

PMID- 29363990
TI  - Multicenter double-blind randomized controlled trial to evaluate the
      effectiveness and safety of bortezomib as a treatment for refractory systemic
      lupus erythematosus.
AB  - OBJECTIVES: The objective of this study is to evaluate the efficacy and safety of
      bortezomib for treating systemic lupus erythematosus (SLE), in patients whose
      disease activity could not be controlled. METHODS: Fourteen SLE patients with
      persistent disease activity were selected, who required prednisolone doses of >10
      mg/d despite concomitant immunosuppressive therapy. Patients were randomly
      administered either bortezomib or a placebo, eight times. The primary and
      secondary end-points were a change in anti-dsDNA antibody titer at week 24 and
      the SLE Responder Index (SRI), respectively. RESULTS: In the bortezomib group,
      four out of eight patients discontinued the trial; three others failed to
      complete the minimum protocol treatment due to adverse reactions. The changes in
      anti-dsDNA antibody titers at week 24 were 4.24% and -1.96%, for the bortezomib
      and placebo groups, respectively, disconfirming bortezomib's efficacy. In
      contrast, the corresponding SRI at week 12 was 75% and 40%. CONCLUSIONS: As
      bortezomib therapy for SLE is associated with many adverse reactions, treatment
      indications should be selected carefully, and protocols should aim to prevent
      these occurrences. Although the change in anti-dsDNA antibody titer did not
      support the efficacy of bortezomib as a treatment for SLE, high SRI in the
      treatment group suggests bortezomib may utilize mechanisms other than inhibition
      of anti-dsDNA antibody production.

PMID- 29363992
TI  - New Approach to Cryopreservation of Primary Noncultivated Human Umbilical Vein
      Endothelium in Biobanking.
AB  - It is widely accepted that endothelial dysfunction (ED) is a common feature and a
      risk factor for cardiovascular diseases and metabolic disorders. Cultures of
      human umbilical vein endothelial cells (HUVECs) are routinely used in cell-based
      models to study in vitro molecular and cellular mechanisms of development of
      different aspects of ED. The methods of the HUVEC extraction and expansion are
      well developed and standardized. However, when large collections of samples are
      needed for certain projects, or when samples from a rare population of patients
      should be collected for future experimental use, HUVEC samples should be
      transferred to a biobank to be saved in liquid nitrogen for a long period of time
      until the required collection is completed. This scenario is not always
      convenient since it requires a lot of effort, a large quantity of expensive
      culture reagents with limited expiration periods, and sometimes special
      facilities and well-trained cell biologists among the biobank staff. In this
      project, we evaluated a method of HUVEC cryopreservation, where the stage of cell
      culturing and expansion before the transfer of samples to the biobank is
      eliminated. A total of 55 samples of umbilical cord (UC) were obtained from women
      immediately after delivery. A primary endothelium pellet derived from 17 UC
      samples was isolated, frozen, and placed in long-term storage in a liquid
      nitrogen freezer. Other samples were used to obtain HUVEC cultures. We have
      demonstrated that cryopreservation of primary endothelium pellets from UC veins
      without culturing and expansion steps does not affect the physiological features
      of HUVECs. This new approach would improve the efficiency of biobanking
      logistics, especially in the case of banking of large collections of endothelial
      samples.

PMID- 29363994
TI  - Improving combination cancer therapy: the CombiPlex(r) development platform.
AB  - Current combination therapy approaches assume that better outcomes are achieved
      by combining drugs at their maximally tolerated doses. However, administration of
      individual agents cannot consistently deliver synergistic drug ratios to tumor
      cells due to differences in pharmacokinetics of the individual drugs. Further,
      the toxicity of combination regimens often necessitates administration of
      suboptimal dosages. Delivery technologies, such as the CombiPlex(r) platform, can
      enable efficient and sustained delivery of combination treatments at a
      synergistic ratio. The CombiPlex platform determines synergistic drug ratios in
      vitro and identifies an appropriate nanoscale carrier to maintain that ratio in
      vivo and enhance its delivery to tumor cells. CPX-351, a dual-drug liposomal
      encapsulation of cytarabine and daunorubicin, is the first clinical proof-of
      concept example of the CombiPlex platform.

PMID- 29363993
TI  - The Contribution of Social Media to Body Dissatisfaction, Eating Disorder
      Symptoms, and Anabolic Steroid Use Among Sexual Minority Men.
AB  - Social media has been associated with body dissatisfaction and eating disorder
      symptoms among young women and adolescent girls. However, despite notable
      evidence of susceptibility to body image pressures, it remains unknown whether
      these associations generalize to sexual minority men. A nationwide sample of
      2,733 sexual minority men completed an online survey advertised to Australian and
      New Zealand users of a popular dating app. Participants answered questions about
      how frequently they used 11 different social media platforms in addition to
      questions about their dating app use, body image, eating disorder symptoms, and
      anabolic steroids. Facebook, Youtube, Instagram, and Snapchat were the most
      frequently used social media platforms. A pattern of small-sized and positive
      associations emerged between social media use and body dissatisfaction, eating
      disorder symptoms, and thoughts about using anabolic steroids. Facebook,
      Instagram, and Snapchat evidenced the strongest associations. The associations of
      social media use with both muscularity dissatisfaction and eating disorder
      symptoms were stronger for image-centric social media platforms (e.g., Instagram)
      than nonimage-centric platforms (e.g., Wordpress); no differences were observed
      for body fat dissatisfaction, height dissatisfaction, or thoughts about using
      anabolic steroids. Previously documented associations of social media use with
      body dissatisfaction and related variables among women and girls appear to
      generalize to sexual minority men. Social media platforms that more centrally
      involve imagery may be of greater concern than nonimage-centric platforms.
      Additional research with sexual minority men is needed to elucidate the
      distinctions between adaptive and maladaptive social media use in the context of
      body dissatisfaction, eating disorders, and anabolic steroid use.

PMID- 29363995
TI  - Heart failure with improved ejection fraction: Is a newcomer in the family
      important?

PMID- 29363996
TI  - Polymorphisms of F2, PROC, PROZ, and F13A1 Genes are Associated With Recurrent
      Spontaneous Abortion in Chinese Han Women.
AB  - Mutations of hemostasis/coagulation-related genes have been speculated to cause
      recurrent spontaneous abortion (RSA). This study investigated the genetic
      association between the polymorphisms of factor V (F5), factor II (F2),
      antithrombin (SERPINC1), protein C (PROC), protein S (PROS1), protein Z (PROZ),
      factor XIII (F13A1), and carboxypeptidase B2 (CPB2) genes and RSA. The 426
      patients with RSA and 444 controls were recruited in this study, and single
      nucleotide polymorphisms (SNPs) were analyzed by using SNPscan technology.
      Genotype and allele frequencies of rs3136520 in F2, rs3024731 in PROZ, and
      rs1050782 in F13A1 showed statistically significant differences between the 2
      groups. TT genotype of rs3136520 ( P = .031, odds ratio [OR] = 0.986, 95%
      confidence interval [CI] = 0.976-0.997) and AA genotype of rs2069906 in PROC ( P
      = .021, OR = 0.114, 95% CI = 0.014-0.902) in their recessive models and AG + GG
      variants of rs1050782 ( P = .007, OR = 0.681, 95% CI = 0.516-0.899) in the
      dominant model might be associated with the reduced risk of RSA. AT + TT variants
      of rs3024731 ( P = .010, OR = 1.479, 95% CI = 1.098-1.994) may increase disease
      susceptibility in dominant model. Haplotype analysis of rs3024731 and rs3024735
      in PROZ displayed that the AA and TG haplotype were inclined to decrease and
      increase the risk of RSA, respectively. These results suggested that rs3136520,
      rs2069906, rs3024731, and rs1050782 may have a significant association with the
      genetic susceptibility of RSA in Chinese Han women.

PMID- 29363997
TI  - Utilizing Fibrin-Alginate and Matrigel-Alginate for Mouse Follicle Development in
      Three-Dimensional Culture Systems.
AB  - In vitro culture of ovarian follicles is a new technique in reproductive
      technology, which helps in understanding the process of folliculogenesis. The in
      vitro culture of follicles could be carried out using three-dimensional (3D)
      natural scaffolds that mimic the ovarian tissue stroma. Selection of the right
      matrix and culture media in these scaffolds could increase the survival and
      maturation of the follicles. In this work, the applicability of matrigel-alginate
      (MA) and fibrin-alginate (FA) 3D scaffolds for folliculogenesis was assessed. The
      ovaries of 13-day-old Naval Medical Research Institute (NMRI) mice were isolated
      and distributed into control and vitrification groups. Preantral follicles (mean
      diameter: 120-140 MUm) were mechanically isolated from control and vitrified
      warmed ovaries, encapsulated in MA or FA scaffold and cultured for 12 days.
      Follicle survival, growth, maturation, and quantitative expression of oocyte
      maturation genes (Gdf9, Bmp15, Fgf8, KitL, Kit, and Amh) and proteins (GDF9 and
      BMP15) were assessed. Survival rate of culture preantral follicles in control
      groups was found to be significantly higher than vitrified follicles. Antrum
      formation was similar in all groups. Follicle diameters were significantly
      increased in all groups during culture period. A decreasing pattern of gene
      expression was seen for all genes in all groups. This trend was verified through
      evaluation of protein expression, during which there was strong staining in
      antral follicles from all groups in the last day of in vitro culture. The better
      survival and maturation rate of follicles in the MA compared to FA scaffold
      indicates that the MA matrix, being rich in extracellular matrix components,
      could mimic the ovarian condition better and presents a good environment for
      follicle development.

PMID- 29363998
TI  - Comparative Evaluation of Biological Performance, Biosecurity, and Availability
      of Cellulose-Based Absorbable Hemostats.
AB  - Hemorrhage remains a leading cause of death after trauma, and developing a
      hemostat with excellent performance and good biosecurity is an extremely active
      area of research and commercial product development. Although oxidized
      regenerated cellulose (ORC) has been developed to address these problems, it is
      not always efficient and its biosecurity is not perfect. We aimed to refine ORC
      via a simple and mild neutralization method. The prepared neutralized oxidized
      regenerated cellulose (NORC) showed a superior gel property due to its chemical
      structure. The biological performance of both ORC and NORC was systematically
      evaluated; the results showed that ORC would induce erythema and edema in the
      irritation test, whereas NORC did not cause any adverse inflammation, indicating
      NORC had desirable biocompatibility. We further demonstrated that NORC confirmed
      to the toxicity requirements of International Organization for Standardization
      (ISO) standards; however, ORC showed an unacceptable cytotoxicity. The rabbit
      hepatic defect model stated that NORC exhibited better ability of hemostasis,
      which was attributed to its significant gel performance in physiological
      environment.

PMID- 29364000
TI  - ISBER Best Practice-Based Education: ISBER-Canadian Tissue Repository Network
      Introduction to Biobanking.

PMID- 29363999
TI  - All-Cause, Stroke/Systemic Embolism-, and Major Bleeding-Related Health-Care
      Costs Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With
      Oral Anticoagulants.
AB  - In this study, all-cause, stroke/systemic embolism (SE)-related, and major
      bleeding (MB)-related health-care costs among elderly patients with nonvalvular
      atrial fibrillation (NVAF) initiating treatment with different oral
      anticoagulants (OACs) were compared. Patients >=65 years of age initiating OACs,
      including apixaban, rivaroxaban, dabigatran, and warfarin, were identified from
      the Humana Research Database between January 1, 2013, and September 30, 2015.
      Propensity score matching was used to separately match the different OAC cohorts
      with the apixaban cohort. All-cause health-care costs and stroke/SE-related and
      MB-related medical costs per patient per month (PPPM) were compared using
      generalized linear or 2-part regression models. Compared to apixaban, rivaroxaban
      was associated with significantly higher all-cause health-care costs (US$2234 vs
      US$1846 PPPM, P < .001) and MB-related medical costs (US$106 vs US$47 PPPM, P <
      .001), dabigatran was associated with significantly higher all-cause health-care
      costs (US$1980 vs US$1801 PPPM, P = .007), and warfarin was associated with
      significantly higher all-cause health-care costs (US$2386 vs US$1929 PPPM, P <
      .001), stroke/SE-related medical costs (US$42 vs US$18 PPPM, P < .001), and MB
      related medical costs (US$132 vs US$51 PPPM, P < .001). Among elderly patients
      with NVAF, other OACs were associated with higher all-cause health-care costs
      than apixaban.

PMID- 29364001
TI  - Perceived personality change after traumatic brain injury II: comparing
      participant and informant perspectives.
AB  - OBJECTIVE: The objective of this paper was to correlate informant personality
      change (PC) judgements following moderate-severe traumatic brain injury with
      quantitative neurobehavioural measures and to contrast the neurobehavioural
      correlates of informant and participant judgements of PC. PARTICIPANTS: Informant
      participant pairs were recruited from a medico-legal clinic passing effort tests
      (N = 31) and a National Health Service clinic (N = 40). MEASURES: Participants
      were assessed on Wechsler tests of general ability, tests of executive
      functioning (Zoo Map and Fluency) and emotional distress (Beck Depression
      Inventory-FastScreen, Hospital Anxiety and Depression Scale and State-Trait Anger
      Expression Inventory-II). Informants' expressed emotion towards participants was
      assessed with the family questionnaire. Both completed the DEX, the Frontal and
      Social Behavior Questionnaire and PC ratings. RESULTS: The correlates of
      participant and informant ratings of participant PC partially overlapped. For
      example, participant self-reported PC was associated with self-reported
      dysexecutive symptoms and emotional distress. In contrast, informant report of
      participant PC was associated with lower perceived emotional recognition and
      empathy, informant report of dysexecutive symptoms and high informant expressed
      emotion. CONCLUSIONS: It is argued that whilst researchers aim to exhaustively
      quantify specific neurobehavioural changes and their clusters, partially
      overlapping subsets of these changes evoke the PC judgements of participants and
      informants. The clinical implications of this are briefly considered.

PMID- 29364002
TI  - Cross-sectional multicentre study on the cohort of all the French junior
      lecturers in general practice.
AB  - BACKGROUND: General practice became an academic discipline quite recently in many
      western countries. In France, junior lecturer work is specified in a three-part
      mandate: medical work in general practice, teaching in the university, and
      research. Since 2007, 130 junior lecturers have been appointed in general
      practice. The aim of the creation of junior lecturer status was to align general
      practice with other specialties and to develop research and education in primary
      care. OBJECTIVES: To describe the healthcare, teaching and research undertaken by
      junior lecturers in general practice, practising in October 2014. METHODS: A
      cross-sectional multicentre study using an online self-administered questionnaire
      on the cohort composed of all the junior lecturers in general practice with open
      questions and the qualitative analysis of written verbatim accounts. RESULTS: Of
      the 95 junior lecturers practising at the date of the study, 75 (79%) responded;
      average age 32 years; gender ratio (F/M) 2.4:1. They spent five, two and three
      half-days per week respectively in healthcare, teaching and research. The
      healthcare activity was predominantly carried out in the community (73%). Thirty
      nine per cent worked as part of a multi-professional team taking on 50
      consultations per week. Most of the educational work involved lecturing and
      mentoring students specializing in general practice (median 86 hours per year).
      Research output increased during the fellowship. Research topics were varied and
      relevant to the disciplinary field. CONCLUSION: During the fellowship, the
      balancing, and even the reinforcement, of healthcare and research contributions
      were accompanied by a significant investment in educational provision.

PMID- 29364003
TI  - Endocardial Changes in Nonvalvular Atrial Fibrillation Without Atrial Thrombus
      Thrombomodulin and Tissue Factor Pathway Inhibitor.
AB  - Atrial fibrillation (AF) is a well-known cause for thromboembolism. Although
      blood stasis in the left atrium and hypercoagulable state of the blood have been
      emphasized as important mechanisms, limited attention has been paid to the
      endocardial changes in maintaining the balance of local coagulation, which may
      also contribute to the thrombus formation in AF. In the present study, left
      atrial appendage samples were obtained at heart surgery from nonvalvular AF and
      non-AF patients without atrial thrombus. Immunohistochemistry for endocardial
      markers including thrombomodulin (TM) and tissue factor pathway inhibitor (TFPI)
      was performed and semiquantitatively graded. In immunohistochemistry analysis,
      decreased expression of TM was found in patients with nonvalvular AF compared
      with those without AF ( P < .001). There was no difference in TFPI expression
      between the 2 groups ( P = .213). Patients with TM score of 0 or 1 seemed to have
      larger left atrial diameter (LAD) than those with TM score of 2 or 3 (44.0 (7.9)
      vs 40.6 (3.9); P = .009), while no relationship between LAD and TFPI expression
      was found (43.4 (7.0) vs 42.9 (7.8); P = .485). In conclusion, TM expression in
      the atrial endocardium is decreased in nonvalvular AF without atrial thrombus,
      while TFPI expression is not. Downregulated TM expression might be associated
      with enlarged LAD.

PMID- 29364005
TI  - Purulent myositis of the thigh as a presentation of perforated low rectal cancer.
AB  - Purulent myositis is an acute, intramuscular bacterial infection involving
      abscess formation most commonly affecting the quadriceps, hamstring and gluteal
      muscles. We present a case of extensive purulent myositis of the thigh and lower
      leg caused by bowel perforation below the peritoneal reflection secondary to
      rectal cancer. Cases of lower limb and perineal purulent myositis should raise
      suspicion of rectal perforation and should prompt investigations to exclude
      rectal malignancy.

PMID- 29364004
TI  - Motorcyclists and pillion passengers with open lower-limb fractures: a study
      using TARN data 2007-2014.
AB  - Introduction We aimed to identify population demographics of motorcyclists and
      pillion passengers with isolated open lower-limb fractures, to ascertain the
      impact of the revised 2009 British Orthopaedic Association/British Association of
      Plastic Reconstructive and Aesthetic Surgeons joint standards for the management
      of open fractures of the lower limb (BOAST 4), in terms of time to skeletal
      stabilisation and soft-tissue coverage, and to observe any impact on patient
      movement. Methods Retrospective cohort data was collected by the Trauma Audit and
      Research Network (TARN). A longitudinal analysis was performed between two
      timeframes in England (pre-and post-BOAST 4 revision): 2007-2009 and 2010-2014.
      Results A total of 1564 motorcyclists and 64 pillion passengers were identified.
      Of these, 93% (1521/1628) were male. The median age for males was 30.5 years and
      36.7 years for females. There was a statistically significant difference in the
      number of patients who underwent skeletal stabilisation (49% vs 65%, P < 0.0001),
      the time from injury to skeletal stabilisation (7.33 hours vs 14.3 hours, P <
      0.0001) and the proportion receiving soft-tissue coverage (26% vs 43%, P <
      0.0001). There was no difference in the time from injury to soft-tissue coverage
      (62.3 hours vs 63.7 hours, P = 0.726). The number of patients taken directly to a
      major trauma centre (or its equivalent) increased between the two timeframes
      (12.5% vs, 41%, P < 0.001). Conclusions Since the 2009 BOAST 4 revision, there
      has been no difference in the time taken from injury to soft-tissue coverage but
      the time from injury to skeletal stabilisation is longer. There has also been an
      increase in patient movement to centres offering joint orthopaedic and plastic
      care.

PMID- 29364006
TI  - Association of pretreatment neutrophil-lymphocyte ratio and outcome in emergency
      colorectal cancer care.
AB  - Introduction The association between the neutrophil-lymphocyte ratio (NLR) and
      outcome in elective colorectal cancer surgery is well established; the
      relationship between NLR and the emergency colorectal cancer patient is, as yet,
      unexplored. This paper evaluates the predictive quality of the NLR for outcome in
      the emergency colorectal cancer patient. Materials and Methods A total of 187
      consecutive patients who underwent emergency surgery for colorectal cancer were
      included in the study. NLR was calculated from the haematological tests done on
      admission. Receiver operating characteristic analyses were used to determine the
      most suitable cut-off for NLR. Outcomes were assessed by mortality at 30 and 90
      days using stepwise Cox proportional hazards regression. Results An NLR cut-off
      of 5 was found to have the highest sensitivity and specificity. At 30 days, age
      and time from admission to surgery were associated with increased mortality; a
      high NLR was associated with an increased risk of mortality in univariate but not
      multivariate analysis. At 90 days, age, NLR, time from admission to surgery and
      nodal status were all significantly associated with increased mortality on
      multivariate analysis. Conclusions Pre-operative NLR is a cheap, easily performed
      and useful clinical tool to aid prediction of outcome in the emergency colorectal
      cancer patient.

PMID- 29364007
TI  - Complication rates of external ventricular drain insertion by surgeons of
      different experience.
AB  - Introduction Insertion of external ventricular drain (EVD) is a widely accepted,
      routinely performed procedure for treatment of hydrocephalus and raised
      intracranial pressure. The purpose of this study was to investigate whether a
      surgeon's experience affects the associated complication rate. Methods This
      retrospective study included all adult patients undergoing EVD insertion at a
      single centre between July 2013 and June 2015. Medical records were retrieved to
      obtain details on patient demographics, surgical indication, risk factors for
      infection and use of anticoagulants or antiplatelets. Surgeon experience,
      operative time, intraoperative antibiotic prophylaxis, need for revision surgery
      and EVD associated infection were examined. Information on catheter tip position
      and radiological evidence of intracranial haemorrhage was obtained from
      postoperative imaging. Results A total of 89 patients were included in the study.
      The overall infection, haemorrhage and revision rates were 4.8%, 7.8% and 13.0%
      respectively, with no significant difference among surgeons of different
      experience. The mean operating time for patients who developed an infection was
      22 minutes while for those without an infection, it was 33 minutes (p=0.474).
      Anticoagulation/antiplatelet use did not appear to increase the rate of
      haemorrhage. The infection rate did not correlate with known risk factors (eg
      diabetes and steroids), operation start time (daytime vs out of hours) or
      duration of surgery although intraoperative (single dose) antibiotic prophylaxis
      seemed to reduce the infection rate. There was also a correlation between longer
      duration of catheterisation and increased risk of infection. Conclusions This is
      the first study demonstrating there is no significant difference in complication
      rates between surgeons of different experience. EVD insertion is a core
      neurosurgical skill and junior trainees should be trained to perform it.

PMID- 29364008
TI  - Computed tomography as a first-line investigation for elderly patients admitted
      to a surgical assessment unit.
AB  - Background Increases in life expectancy has meant that a higher proportion of
      patients presenting to surgical assessment units are now elderly. Abdominal
      computed tomography (CT) can provide early and accurate diagnosis in the elderly,
      even in the presence of incomplete clinical and biological findings. The aim of
      this study was to investigate the use of early CT imaging in elderly patients
      presenting directly to the surgical assessment unit. Materials and methods All
      consecutive patients aged 65 years and over admitted directly to the surgical
      assessment unit between January 2017 and April 2017 were identified. Data were
      collected on demographics, laboratory investigations, radiological investigations
      and hospital admission. The primary outcome measure was overall length of stay.
      Results A total of 200 consecutive patients were identified and included over a
      six-month period. This comprised 110 women and 90 men with a median age of 78
      years (range 64-98 years). A total of 83 patients underwent CT on admission to
      the surgical assessment unit. White cell count (WCC) and C-reactive protein (CRP)
      results were significantly higher in patients undergoing CT (P = 0.001). Median
      length of stay for patients undergoing CT was 5 days (range 1-19 days). This was
      significantly lower than those patients not receiving CT imaging, at 6 days
      (range 1-105 days; P = 0.034). Discussion CT should be considered as a first-line
      investigation when elderly patients with an acute abdomen are admitted to
      surgical assessment units. Early CT can accelerate hospital discharge and
      decrease overall length of hospital stay.

PMID- 29364009
TI  - Laparoscopic aproach in post-traumatic chylous ascites.
AB  - Chylous ascites is a rare condition little reported in literature, with even more
      exceptional traumatic origin. Its production mechanism is not known exactly but
      has been attributed to hyperflexion or hyperextension of the spine leading to a
      rupture of lymph ducts. We present a case of post-traumatic chyloperitoneum in a
      young patient after abdominal blunt trauma. Conservative treatment should be the
      first therapeutic option, especially if the origin is traumatic, reserving more
      aggressive possibilities for cases that do not respond after 15 days, if debt is
      greater than 1.5 litres/day in adult patients or in those with metabolic
      complications. A laparoscopic approach is indicated to confirm the diagnosis and
      to rule out other associated injuries that may require other surgical procedures.

PMID- 29364010
TI  - The Patient Concerns Inventory integrated as part of routine head and neck cancer
      follow-up consultations: frequency, case-mix, and items initiated by the patient.
AB  - Introduction The National Institute for Health and Care Excellence guidance
      Improving Supportive and Palliative Care for Adults with Cancer (2004) and the
      Cancer Reform Strategy (2007) support the premise that assessment and discussion
      of patients' needs for physical, social, psychological, and spiritual wellbeing
      should be undertaken during oncology follow-up. We report the use of the Patient
      Concerns Inventory in a routine head and neck cancer clinic setting over a seven
      year period, summarising the number of available clinics, the number of patients
      completing the inventory within a clinic, the range of clinical characteristics
      and the concerns they wanted to discuss. Methods The data were analysed from
      oncology follow-up clinics between 1 August 2007 and 10 December 2014. Audit
      approval was given by the Clinical Audit Department, University Hospital Aintree.
      Results There were 386 patients with 1198 inventories completed at 220 clinics,
      median 6 (range 4-7) per clinic. The most common concerns raised by patients
      across all the clinic consultations were dry mouth (34%), fear of recurrence
      (33%), sore mouth (26%), dental health (25%), chewing (22%) and fatigue/tiredness
      (21%). Conclusions The incorporation of the Patient Concerns Inventory as part of
      routine oncology clinics allows for a more patient initiated and focused
      consultation available to the majority of patients throughout their follow-up.
      The inventory allows for greater opportunity to provide holistic targeted
      multiprofessional intervention and support.

PMID- 29364011
TI  - Outcomes of surgery in patients aged >=90 years in the general surgical setting.
AB  - Introduction An increasing proportion of the population is living into their
      nineties and beyond. These high risk patients are now presenting more frequently
      to both elective and emergency surgical services. There is limited research
      looking at outcomes of general surgical procedures in nonagenarians and
      centenarians to guide surgeons assessing these cases. Methods A retrospective
      analysis was conducted of all patients aged >=90 years undergoing elective and
      emergency general surgical procedures at a tertiary care facility between 2009
      and 2015. Vascular, breast and endocrine procedures were excluded. Patient
      demographics and characteristics were collated. Primary outcomes were 30-day and
      90-day mortality rates. The impact of ASA (American Society of Anesthesiologists)
      grade, operation severity and emergency presentation was assessed using
      multivariate analysis. Results Overall, 161 patients (58 elective, 103 emergency)
      were identified for inclusion in the study. The mean patient age was 92.8 years
      (range: 90-106 years). The 90-day mortality rates were 5.2% and 19.4% for
      elective and emergency procedures respectively (p=0.013). The median survival was
      29 and 19 months respectively (p=0.001). Emergency and major gastrointestinal
      operations were associated with a significant increase in mortality. Patients
      undergoing emergency major colonic or upper gastrointestinal surgery had a 90-day
      mortality rate of 53.8%. Conclusions The risk for patients aged over 90 years
      having an elective procedure differs significantly in the short term from those
      having emergency surgery. In selected cases, elective surgery carries an
      acceptable mortality risk. Emergency surgery is associated with a significantly
      increased risk of death, particularly after major gastrointestinal resections.

PMID- 29364012
TI  - Ileocecal intussusception extending to left colon due to endometriosis.
AB  - Bowel involvement in endometriosis is uncommon and is most frequently located in
      the sigmoid colon and the rectum. We present a case in a 37-year-old woman of a
      cecal endometrioid mass complicated with an ileocolic intussusception which
      extended beyond the splenic colon flexure. Careful manual extraction allowed a
      reduction of the intussusceptum, followed by an oncological right hemicolectomy.
      The patient suffered postoperative ileus, which was spontaneously solved.
      Intussusception is infrequent in the adult population and usually involves the
      small bowel. The great majority of ileocolic intussusceptions have a malignant
      origin (cecal adenocarcinoma). An endometriotic mass located at the cecum as the
      lead point for ileocolic intussusception is an extremely rare presentation. On
      reviewing the literature, we found only 13 reports with no other cases extending
      beyond the splenic flexure, as occurred in our patient.

PMID- 29364013
TI  - Introduction into the NHS of magnetic sphincter augmentation: an innovative
      surgical therapy for reflux - results and challenges.
AB  - Introduction Gastro-oesophageal reflux disease (GORD) is a common, chronic
      debilitating condition. Surgical management traditionally involves
      fundoplication. Magnetic sphincter augmentation (MSA) is a new definitive
      treatment. We describe our experience of introducing this innovative therapy into
      NHS practice and report the early clinical outcomes. Methods MSA was introduced
      into NHS practice following successful acceptance of a cost-effective business
      plan and close observation of National Institute for Health and Care Excellence
      (NICE) recommendations for new procedures, including a carefully planned
      prospective data collection over a two-year follow-up period. Results Forty-seven
      patients underwent MSA over the 40-month period. Reflux health-related quality of
      life (GERD-HRQL) was significantly improved after the procedure and maintained at
      one- and two-year (P < 0.0001) follow-up. Drug dependency went from 100% at
      baseline to 2.6% and 8.7% after one and two years. High levels of patient
      satisfaction were reported. There were no adverse events. Conclusions MSA is
      highly effective in the treatment of uncomplicated GORD, with durable results and
      an excellent safety profile. This laparoscopic, minimally invasive procedure
      provides a good alternative for patients where surgical anatomy is unaltered. Our
      experience demonstrates that innovative technology can be incorporated into NHS
      practice with an acceptable business plan and compliance with NICE
      recommendations.

PMID- 29364014
TI  - Lidocaine analgesia for removal of vacuum-assisted closure dressings.

PMID- 29364015
TI  - Comparison of defecatory function after laparoscopic total colectomy and
      ileorectal anastomosis versus a traditional open approach.
AB  - Introduction Total colectomy and ileorectal anastomosis can result in significant
      defecatory frequency and poor bowel function. The aim of this study was to assess
      whether a laparoscopic approach is associated with any improvement in this
      regard. Methods A single institution retrospective review was undertaken of
      patients undergoing elective total colectomy and ileorectal anastomosis between
      2000 and 2011. Those undergoing emergency surgery and paediatric surgery were
      excluded. The primary outcome measure was satisfactory defecatory function after
      surgery. Results Forty-nine patients (24 male, 25 female) were included in the
      study. The median age was 48 years (range: 20-83 years). Laparoscopic total
      colectomy (LTC) was performed in 20 patients and open total colectomy (OTC) in 29
      patients. Indications for surgery were slow colonic transit (n=17), colorectal
      cancer (CRC) (n=17), CRC with hereditary colorectal cancer syndrome (n=8),
      inflammatory bowel disease (n=4) and diverticular disease (n=3). In the LTC
      group, 85% had a satisfactory defecatory frequency of 1-6 motions per day
      compared with 45% in the OTC cohort (p=0.006). There was no statistically
      significant difference in bowel frequency related to primary pathology (benign vs
      cancer surgery, p=1.0). Postoperative complications for both groups included
      relaparotomy (n=3), anastomotic leak (n=2), small bowel obstruction (n=2),
      postoperative bleeding (n=1) and pneumonia (n=1). Conclusions This study
      indicates that long-term defecatory function is better following LTC than
      following OTC and ileorectal anastomosis. The mechanism for this improvement is
      unclear but it may relate to the underlying reason for surgery or possibly to
      reduced small bowel handling leading to fewer adhesions after laparoscopic
      surgery.

PMID- 29364016
TI  - Impact of laparoscopic approach in emergency major abdominal surgery: single
      centre analysis of 748 consecutive cases.
AB  - BackgroundAcute abdominal pathology requiring emergency laparotomy is a common
      surgical presentation. Despite its widespread implementation in other surgical
      procedures, laparoscopy, rather than laparotomy, is sparingly used in major
      emergency surgery. This study reports outcomes and impact of rising use of
      laparoscopy for a single high-volume district general hospital.MethodsData were
      retrieved from the prospective National Emergency Laparotomy Audit database for a
      30-month period. Patient, procedural, and in-hospital outcome data were collated.
      Temporal trends were assessed and regression analysis conducted for clinical
      outcomes.ResultsA total of 748 consecutive cases were recorded. There was an
      increasing use of laparoscopy over the study period, with 49% of cases attempted
      laparoscopically in the final six-month interval. Patients treated
      laparoscopically were at reduced risk of mortality (odds ratio 0.114, 95%
      confidence interval 0.024 to 0.550) and experienced reduced length of intensive
      care stay (regression coefficient -1.571, 95% confidence interval -2.625 to 
      0.517) in multivariate adjusted analysis.ConclusionsLaparoscopy is safe and
      feasible in a large proportion of cases. It is associated with improved outcomes
      versus laparotomy.

PMID- 29364017
TI  - VRAM steal syndrome - a unique cause of flap necrosis in chest wall
      reconstruction.
AB  - The pedicled vertical rectus abdominis myocutaneous (VRAM) flap is a robust flap,
      which is considered to be a 'workhorse' regional option for chest wall
      reconstruction. We describe a previously unreported complication of partial flap
      loss due to 'steal syndrome', whereby arterial supply was diverted away from the
      flap due to dialysis from an ipsilateral arteriovenous fistula.

PMID- 29364018
TI  - Renal pseudoaneurysm: a rare and potentially fatal complication following
      ureteroscopy and laser fragmentation of stones.
AB  - Ureteroscopy and laser fragmentation of stones is a commonly used method to treat
      ureteric and renal calculi. We report the exceedingly rare finding of a renal
      pseudoaneurysm in an interpolar renal artery following ureteroscopy and laser
      stone fragmentation, which was successfully managed with angioembolisation.

PMID- 29364019
TI  - NICE guidance on sepsis is of limited value in postoperative colorectal patients:
      the scores that cry 'wolf!'
AB  - Background and aims Late recognition of sepsis and consequent death remains a
      problem. To address this, the National Institute for Health and Care Excellence
      has published updated guidance recommending the use of the Quick Sequential Organ
      Failure Assessment (Q-SOFA) score when assessing patients at risk of sepsis
      following the publication of the Third International Consensus Definitions for
      Sepsis and Septic Shock. The trauma from major surgery produces a systemic
      inflammatory response syndrome (SIRS) postoperatively as part of its natural
      history, which may falsely trigger scoring systems. We aimed to assess the
      accuracy of Q-SOFA and SIRS criteria as recommended scores for early detection of
      sepsis and septic complications in the first 48hrs after colorectal cancer
      surgery. Methods We reviewed all elective major colorectal operations in a single
      centre during a 12-month period from prospectively maintained electronic records.
      Results One hundred and thirty nine patients were included in this study. In all,
      29 patients developed postoperative infective complications in hospital. Nineteen
      patients triggered on SIRS without developing infective complications, while 42
      patients triggered on Q-SOFA with no infective complications. The area under the
      ROC curve was 0.52 for Q-SOFA and 0.67 for SIRS. Discussion Q-SOFA appears to
      perform little better than a coin toss at identifying postoperative sepsis after
      colorectal cancer resection and is inferior to the SIRS criteria. More work is
      required to assess whether a combination of scoring criteria, biochemical markers
      and automated tools could increase accurate detection of postoperative infection
      and trigger early intervention.

PMID- 29364020
TI  - Drape crimping: a novel technique for retracting skin flaps.

PMID- 29364021
TI  - A tale of three stents: aortic stenting prior to oesophagectomy after oesophageal
      stents.
AB  - The use of endoluminal stents to treat anastomotic leaks post oesophagogastric
      resection remains controversial. While some advocate stents to expedite recovery,
      others advise caution due to the risk of major morbidity and mortality. We
      describe a case of anastomotic leak following total gastrectomy for
      adenocarcinoma treated with a self-expanding metallic stent. Complications with
      the initial stent were treated with a further stent, which compromised the
      function of the oesophagus and eroded into the aorta, necessitating a colonic
      reconstruction and endovascular aortic stenting.

PMID- 29364022
TI  - Micromanaging the gut: unravelling the regulatory pathways that mediate the
      intestinal adaptive response.
AB  - Short bowel syndrome occurs following the loss of a large portion of functional
      intestine and is associated with high morbidity and mortality. The intestine
      exhibits pronounced diurnal rhythms in glucose absorption and mounts a profound
      proliferative response following massive small bowel resection. Understanding the
      molecular pathways that underpin this could yield novel treatment options. Two in
      vivo models were employed using the nocturnally active Sprague Dawley(r) rat,
      namely daytime feeding and massive small bowel resection. Glucose absorption
      exhibited a 24-hour periodicity in the gut and peaked during maximal nutrient
      delivery, mediated by rhythms in the glucose transporter sodium glucose co
      transporter 1 (SGLT1). Feeding during the day shifted the peak in the circadian
      clock gene PER1 and SGLT1. RNA interference and luciferase assays demonstrated
      that PER1 transcriptionally regulates SGLT1, linking for the first time clock
      genes and intestinal glucose absorption. Intestinal proliferation also exhibited
      diurnal rhythmicity, with peak absorptive surface area occurring during maximal
      nutrient availability. mir-16 is diurnally expressed in intestinal crypts,
      exhibiting minimal expression during maximal nutritional availability. mir-16
      overexpression increased apoptosis and arrested proliferation in vitro. mir-125a
      was upregulated in intestinal crypts following 80% small bowel resection, and
      induced apoptosis and growth arrest upon overexpression in vitro. This work
      provides novel insights into the role of circadian clock genes, intestinal
      transporters and microRNAs in regulating intestinal absorption and proliferation
      and is the first demonstration of a role for microRNAs in these adaptive
      phenomena. Modulation of these pathways may represent a new therapeutic option
      for the management of short bowel syndrome.

PMID- 29364023
TI  - Snapping Biceps Femoris: clinical demonstration and operative technique.
AB  - Snapping biceps femoris syndrome has been reported in the literature in a handful
      of case reports but not yet with a demonstration of clinical examination and
      intraoperative findings. We present an educational clinical video of snapping
      biceps femoris with intraoperative demonstration of findings and surgical repair.

PMID- 29364024
TI  - Clinician modifiable factors associated with better quality of life in children
      with acquired brain injury undergoing rehabilitation.
AB  - OBJECTIVES: To identify clinician-modifiable factors related to quality of life
      (QOL) in children with acquired brain injury (ABI). PARTICIPANTS AND METHODS:
      Thirty-nine children attending an ABI rehabilitation program (5-18 years) were
      assessed using the Personality Inventory for Children-2, Vineland Adaptive
      Behavior Scale-2, Handicap-Related Problems for Parents Inventory and Children's
      Assessment of Participation and Enjoyment. The Pediatric Quality of Life
      Inventory was completed by children and parents six months later. RESULTS:
      Children with lower levels of internalising and externalising behaviours, health
      and social skill problems, and higher family functioning had significantly higher
      levels of total QOL (child and parent rated) (r = -.47 to -.79). In addition,
      children with higher levels of adaptive behaviour had significantly higher parent
      rated total QOL (r = .46). Measures of mother's stressors had moderate but not
      statistically significant relationships with the child's total QOL (r = -.31 to 
      .35). There were moderate and statistically significant relationships between
      measures of participation in physical activities and total QOL as rated by
      children (r = .42-.48) but not parents (r = .11-.30). CONCLUSIONS: These findings
      suggest potential targets to be investigated in future clinical research in
      rehabilitation following ABI in children to optimise QOL.

PMID- 29364025
TI  - The Utilization of Interval Throwing Programs in the Physical Therapy Setting - A
      Cross-Sectional Survey.
AB  - CONTEXT: Interval throwing programs (ITP) have long been used in the physical
      therapy setting to aid in the safe and efficacious return to sport for an
      overhead athlete. However, the overall utilization and variation of interval
      throwing programs are unknown in the physical therapy setting leading to
      potential inconsistencies in treatment paradigms. OBJECTIVE: To determine if
      differences in practice patterns exist among active physical therapists of
      various experience levels with regards to years of experience and advanced
      certifications. DESIGN: Cross-sectional survey study. PARTICIPANTS: 133 licensed
      physical therapists consented to participate in an online-based survey.
      Experience groups were delineated based on years of practice (0-1, 1-5, 6-15,
      15+) and possession of advanced certification. MAIN OUTCOME MEASURES: For ranking
      based data, a generalized linear mixed-model was repeated across criteria
      response with a Bonferroni Post-Hoc adjustment for pairwise comparisons made
      within and between groups (alpha < 0.05). For degree-based questions, chi-square
      analysis was used to compare response frequencies for options provided within
      each question. RESULTS: A 76.7% response-rate was achieved with 102 out of the
      133 consenting individuals completed the survey. Significant differences (p<0.05)
      were found with responses to both ranking-based and degree-based questions.
      However, across all groups, physical therapists agreed that throwing mechanics
      and customized ITP implementation were important for a successful return to
      throwing. CONCLUSIONS: There are inherent differences in ITP prescription among
      physical therapists with dissimilar experience levels. The possession of advanced
      certifications and years of practice seem to play a role in how interval programs
      are prescribed to overhead throwing athletes. This study helps to identify
      differences in current physical therapy approaches towards the later stages of
      rehabilitation for throwing athletes. Further research should identify areas of
      improvement in physical therapist education as well as appropriate ITP
      prescription parameters to optimize care and treatment for this patient
      population.

PMID- 29364026
TI  - Effects of a 4-Week Intrinsic Foot Muscle Exercise Program on Motor Function: A
      Preliminary Randomized Control Trial.
AB  - CONTEXT: Intrinsic foot muscle (IFM) exercises are utilized clinically in the
      treatment of foot and ankle conditions. However, the effectiveness of training on
      IFM motor function is unknown. OBJECTIVE: To study the effects of a 4-week IFM
      exercise program on motor function, perceived difficulty, and IFM motor
      activation measured using ultrasound imaging (USI) during three IFM exercises.
      DESIGN: Single-blinded randomized control trial. SETTING: Laboratory.
      PARTICIPANTS: 24 healthy, recreationally-active young adults without history of
      ankle-foot injury who have never performed IFM exercises participated (12 males,
      12 females; mean age=21.5+/-4.8 years; BMI=23.5+/-2.9 kg/m2) Intervention:
      Following randomization, participants allocated to the intervention group
      received a 4-week progressive home IFM exercise program performed daily.
      Participants in the control group did not receive any intervention. MAIN OUTCOME
      MEASURES: Clinician-assessed motor performance (4-point scale: 0=does not
      initiate movement, 3=performs exercise in standard pattern), participant
      perceived difficulty (5 point Likert scale: 1=very easy, 5=very difficult), and
      USI motor activation measures [Formula: see text] of the abductor hallucis
      (AbdH), flexor digitorum brevis (FDB), quadratus plantae (QP), and flexor
      hallucis brevis (FHB) were assessed during a toe-spread-out, hallux-extension,
      and lesser-toe-extension exercise. RESULTS: The intervention group demonstrated
      significant improvement in motor performance in the toe-spread-out exercise
      (pre=1.9+/-0.5, post=2.6+/-0.5, p=.008) and less perceived difficulty in the toe
      spread-out (pre=3.1+/-1.3, post=2.3+/-1.2, p=.01), hallux-extension (pre=3.2+/
      1.5, post=2.0+/-1.2, p=.005), and lesser-toe-extension (pre=1.9+/-0.7, post=1.2+/
      0.4, p=.03) exercises. Both groups demonstrated increased USI motor activation in
      the AbdH during the toe-spread-out exercise (intervention: pre=1.07+/-.06,
      post=1.11+/-.08; control: pre=1.08+/-.06, post=1.11+/-.06, p=.05). No other
      significant main effects or group by time interactions were observed. CONCLUSION:
      A 4-week IFM exercise intervention resulted in improved motor performance and
      decreased perceived difficulty when performing the exercises, but not changes in
      USI measures of IFM activation compared to a control group.

PMID- 29364027
TI  - Effects of Kinesiology Taping on Scapular Reposition Accuracy, Kinematics, and
      Muscle Activity in Athletes With Shoulder Impingement Syndrome: A Randomized
      Controlled Study.
AB  - CONTEXT: Scapular proprioception is a key concern in managing shoulder
      impingement syndrome (SIS). However, no study has examined the effect of elastic
      taping on scapular proprioception performance. OBJECTIVE: To investigate the
      immediate effect of kinesiology taping (KT) on scapular reposition accuracy,
      kinematics, and muscle activation in individuals with SIS. DESIGN: Randomized
      controlled study. SETTING: Musculoskeletal laboratory, National Yang-Ming
      University, Taiwan. PARTICIPANTS: Thirty overhead athletes with SIS.
      INTERVENTIONS: KT or placebo taping over the upper and lower trapezius muscles.
      MAIN OUTCOME MEASURES: The primary outcome measures were scapular joint position
      sense, measured as the reposition errors, in the direction of scapular elevation
      and protraction. The secondary outcomes were scapular kinematics and muscle
      activity of the upper trapezius, lower trapezius, and serratus anterior during
      arm elevation in the scapular plane (scaption). RESULTS: Compared with placebo
      taping, KT significantly decreased the reposition errors of upward/downward
      rotation (P = .04) and anterior/posterior tilt (P = .04) during scapular
      protraction. KT also improved scapular kinematics (significant group by taping
      effect for posterior tilt, P = .03) during scaption. Kinesiology and placebo
      tapings had a similar effect on upper trapezius muscle activation (significant
      taping effect, P = .003) during scaption. CONCLUSIONS: Our study identified the
      positive effects of KT on scapular joint position sense and movement control.
      Future studies with a longer period of follow-up and clinical measurement might
      help to clarify the clinical effect and mechanisms of elastic taping in
      individuals with SIS.

PMID- 29364028
TI  - A Comparison of Bilateral and Unilateral Drop Jumping Tasks in the Assessment of
      Vertical Stiffness.
AB  - This study sought to compare vertical stiffness during bilateral and unilateral
      drop jumping. Specifically, the intersession reliabilities and force-deformation
      profiles associated with each task were to be examined. On 3 occasions, following
      familiarization, 14 healthy males (age: 22 [2] y; height: 1.77 [0.08] m; and body
      mass: 73.5 [8.0] kg) performed 3 bilateral, left leg and right leg drop jumps.
      All jumps were performed from a drop height of 0.18 m on to a dual force plate
      system. Vertical stiffness was calculated as the ratio of peak ground reaction
      force (GRF) to the peak center of mass (COM) displacement. Unilateral drop
      jumping was associated with higher GRF and greater COM displacement (both Ps <
      .001), but vertical stiffness was not different between tasks when considering
      individual limbs (P = .98). A coefficient of variation of 14.6% was observed for
      bilateral vertical stiffness during bilateral drop jumping; values of 6.7% and
      7.6% were observed for left and right limb vertical stiffness during unilateral
      drop jumping. These findings suggest that unilateral drop jumps may exhibit
      greater reliability than bilateral drop jumps while eliciting similar vertical
      stiffness. It is also apparent that higher GRFs during unilateral drop jumping
      are mitigated by increased COM displacement.

PMID- 29364029
TI  - Remediation of water and wastewater by using engineered nanomaterials: A review.
AB  - Nanotechnology is currently a fast-rising socioeconomic and political knowledge
      based technology owing to the unique characteristics of its engineered
      nanomaterials. This branch of technology is useful for water and wastewater
      remediation. Many scientists and researchers have been conducting different
      studies and experiments on the applications of engineered nanomaterials at the
      local to international level. This review mainly aims to provide a current
      overview of existing knowledge on engineered nanomaterials and their applications
      in water and wastewater remediation. Furthermore, the present risks and
      challenges of nanotechnology are examined.

PMID- 29364030
TI  - Hydraulic and hydrological aspects of an evapotranspiration-constructed wetland
      combined system for household greywater treatment.
AB  - Constructed wetlands systems demand preliminary and primary treatment to remove
      solids present in greywater (GW) to avoid or reduce clogging processes. The
      current paper aims to assess hydraulic and hydrological behavior in an improved
      constructed wetland system, which has a built-in anaerobic digestion chamber
      (AnC), GW is distributed to the evapotranspiration and treatment tank (CEvaT),
      combined with a subsurface horizontal flow constructed wetland (SSHF-CW). The
      results show that both the plants present in the units and the AnC improve
      hydraulic and volumetric efficiency, decrease short-circuiting and improve mixing
      conditions in the system. Moreover, the hydraulic conductivity measured on-site
      indicates that the presence of plants in the system and the flow distribution
      pattern provided by the AnC might reduce clogging in the SSHF-CW. It is observed
      that rainfall enables salt elimination, thus increasing evapotranspiration (ET),
      which promotes effluent reduction and enables the system to have zero discharge
      when reuse is unfeasible.

PMID- 29364031
TI  - Hereditary cataracts in Russian Blue cats.
AB  - OBJECTIVES: The purpose of this study was to investigate the prevalence of
      cataracts in the Russian Blue breed of cats in Sweden, and to describe the
      clinical appearance of this presumed inherited form of cataract. METHODS: A total
      of 66 Russian Blue cats were examined in Sweden, between March and October 2014,
      using standard examination techniques. The examined cats were between 3 months
      and 14 years of age. Pedigrees were collected from all examined cats for genetic
      studies. RESULTS: Mild-to-severe forms of mainly bilateral cataracts were
      observed in 22/66 examined Russian Blue cats of both sexes. Two affected cats
      were <1 year of age. The most frequently observed appearance of a cataract was a
      small triangular, Y-shaped or circular opacity at the border of the posterior
      nucleus and the anterior part of the posterior cortex, which caused no observable
      visual impairment. More extended forms were observed in 6/22 cats, with
      involvement of both the nucleus and either the entire cortex or parts of the
      posterior and/or anterior cortex. Visual impairment or blindness was observed in
      the latter six cases. Pedigree analyses indicated a simple autosomal recessive
      mode of inheritance for the defect, although a dominant mode with incomplete
      penetrance could not be excluded. CONCLUSIONS AND RELEVANCE: This study indicates
      that the Russian Blue breed of cat is affected by hereditary cataracts. The high
      prevalence in young cats and the characteristic location of the most frequently
      observed defect in the study suggest an early onset type of cataract. The
      breeders should be aware of this defect and have their cats examined by a
      veterinary ophthalmologist before breeding of an individual Russian Blue cat is
      considered.

PMID- 29364032
TI  - Feline primary erythrocytosis: a multicentre case series of 18 cats.
AB  - CASE SERIES SUMMARY: A retrospective multicentre case series of feline primary
      erythrocytosis (PE) was evaluated. The aim was to gain better understanding of
      disease presentation and progression to guide management and prognostication.
      Case records were assessed for evidence of increased packed cell volume (PCV;
      >48%), sufficient investigation to rule out relative and secondary
      erythrocytosis, and follow-up data for at least 12 months or until death.
      Eighteen cats were included in the case series. No significant trends in
      signalment were noted. Seizures and mentation changes were the most common
      presenting signs (both n = 10). Median PCV was 70% (median total protein
      concentration of 76 g/l) with no other consistent haematological changes. Sixteen
      cats survived to discharge. Phlebotomy was performed initially in 15/16 surviving
      animals and performed after discharge in 10/16. Hydroxyurea was the most common
      adjunctive therapy, used in 10/16 cats. Of the 16 patients surviving to
      discharge, 14 patients were still alive at the conclusion of the study (survival
      time >17 months post-discharge), with the two non-survivors having lived for 5
      years or more after diagnosis. PCV, when stabilised, did not correlate with
      resolution of clinical signs. RELEVANCE AND NOVEL INFORMATION: In contrast to
      perceptions, feline PE was generally well managed via a combination of phlebotomy
      and medical therapy, with evidence of prolonged survival times. The use of
      hydroxyurea enabled cessation or repeat phlebotomies.

PMID- 29364033
TI  - The Effects of Cupping on Hamstring Flexibility in Collegiate Soccer Players.
AB  - CONTEXT: Collegiate soccer players suffer hamstring injuries due to inflexibility
      and repetitive motions involving intense hamstring lengthening and contraction
      during sport. Although a popular intervention for muscular injury, there exists
      limited evidence of the effects of therapeutic cupping on hamstring flexibility.
      OBJECTIVE: To determine the effect of cupping therapy on hamstring flexibility in
      collegiate soccer players. DESIGN: Cohort design. SETTING: Athletic training
      clinic. PATIENTS: Twenty-five, asymptomatic, NCAA Division III soccer players (10
      males, 15 females) (age = 19.4 +/- 1.30 years, height = 175.1 +/- 8.2 cm, mass =
      69.5 +/- 6.6 kg). INTERVENTION(S): A 7-minute therapeutic cupping treatment was
      delivered to the treatment group. Four 2-inch cups were fixed atop trigger point
      locations within the hamstring muscle bellies of participants' dominant legs.
      Control group participants received no intervention between pre- and post-test
      measurements. MAIN OUTCOME MEASURES: Pretest and posttest measurements of
      hamstring flexibility, using a Passive Straight Leg Raise (PSLR), were performed
      on both groups. PSLR measurements were conducted by blinded examiners using a
      digital inclinometer. An independent samples t-test was used to analyze changes
      in hamstring flexibility from pre- to post-treatment with p-values set a priori
      at 0.05. RESULTS: An independent samples t-test demonstrated no significant
      difference in change in hamstring flexibility between participants in the
      treatment group and those in the control group (t23 = -.961, p = .35).
      CONCLUSIONS: The findings of this study demonstrated no statistically significant
      changes in hamstring flexibility following a cupping treatment.

PMID- 29364034
TI  - Medial Unloader Braces and Lateral Heel Wedges Do Not Alter Gait Biomechanics in
      Healthy Young Adults.
AB  - CONTEXT: Orthotic devices such as medial unloader knee braces and lateral heel
      wedges may limit cartilage loading following trauma or surgical repair. However,
      little is known regarding their effects on gait biomechanics in young, healthy
      individuals who are at risk of cartilage injury during physical activity due to
      greater athletic exposure compared to older adults. OBJECTIVE: Determine the
      effect of medial unloader braces and lateral heel wedges on lower extremity
      kinematics and kinetics in healthy, young adults. DESIGN: Cross-sectional cross
      over design. SETTING: Laboratory setting. PATIENTS: Healthy, young adults who
      were recreationally activity (30 min/day for 3 days/week) between 18-35 years old
      who were free from orthopedic injury for at least 6 months and no history of
      lower extremity orthopedic surgery. INTERVENTIONS: All subjects completed normal
      over ground walking with a medial unloader brace at two different tension
      settings and a lateral heel wedge for a total of four separate walking
      conditions. MAIN OUTCOME MEASURES: Frontal plane knee angle at heelstrike, peak
      varus angle, peak internal knee valgus moment, and frontal plane angular impulse
      were compared across conditions. RESULTS: The medial unloader brace at 50% (-2.04
      +/- 3.53 degrees ) and 100% (-1.80 +/- 3.63 degrees ) maximum load placed the
      knee in a significantly more valgus orientation at heelstrike compared to the
      lateral heel wedge condition (-0.05 +/- 2.85 degrees ). However this difference
      has minimal clinical relevance. Neither of the orthotic devices altered knee
      kinematics or kinetics relative to the control condition. CONCLUSIONS: Though
      effective in older adults and individuals with varus knee alignment, medial
      unloader braces and lateral heel wedges do not influence gait biomechanics in
      young, healthy individuals.

PMID- 29364036
TI  - Six Sessions of Anterior-to-Posterior Ankle Joint Mobilizations Improve Patient
      Reported Outcomes in Patients With Chronic Ankle Instability: A Critically
      Appraised Topic.
AB  - Clinical Scenario: Chronic ankle instability (CAI) is a complex musculoskeletal
      condition that results in sensorimotor and mechanical alterations. Manual
      therapies, such as ankle joint mobilizations, are known to improve clinician
      oriented outcomes like dorsiflexion range of motion, but their impact on patient
      reported outcomes remains less clear. Focused Clinical Question: Do anterior-to
      posterior ankle joint mobilizations improve patient-reported outcomes in patients
      with chronic ankle instability? Summary of Key Findings: Three studies (2
      randomized controlled trials and 1 prospective cohort) quantified the effect of
      at least 2 weeks of anterior-to-posterior ankle joint mobilizations on improving
      patient-reported outcomes immediately after the intervention and at a follow-up
      assessment. All 3 studies demonstrated significant improvements in at least 1
      patient-reported outcome immediately after the intervention and at the follow-up
      assessment. Clinical Bottom Line: At least 2 weeks of ankle joint mobilization
      improves patient-reported outcomes in patients with chronic ankle instability,
      and these benefits are retained for at least a week following the termination of
      the intervention. Strength of Recommendation: Strength of recommendation is grade
      A due to consistent good-quality patient-oriented evidence.

PMID- 29364035
TI  - Regulator of G protein signaling-12 modulates the dopamine transporter in ventral
      striatum and locomotor responses to psychostimulants.
AB  - Regulators of G protein signaling are proteins that accelerate the termination of
      effector stimulation after G protein-coupled receptor activation. Many regulators
      of G protein signaling proteins are highly expressed in the brain and therefore
      considered potential drug discovery targets for central nervous system
      pathologies; for example, here we show that RGS12 is highly expressed in
      microdissected mouse ventral striatum. Given a role for the ventral striatum in
      psychostimulant-induced locomotor activity, we tested whether Rgs12 genetic
      ablation affected behavioral responses to amphetamine and cocaine. RGS12 loss
      significantly decreased hyperlocomotion to lower doses of both amphetamine and
      cocaine; however, other outcomes of administration (sensitization and conditioned
      place preference) were unaffected, suggesting that RGS12 does not function in
      support of the rewarding properties of these psychostimulants. To test whether
      observed response changes upon RGS12 loss were caused by changes to dopamine
      transporter expression and/or function, we prepared crude membranes from the
      brains of wild-type and RGS12-null mice and measured dopamine transporter
      selective [3H]WIN 35428 binding, revealing an increase in dopamine transporter
      levels in the ventral-but not dorsal-striatum of RGS12-null mice. To address
      dopamine transporter function, we prepared striatal synaptosomes and measured
      [3H]dopamine uptake. Consistent with increased [3H]WIN 35428 binding, dopamine
      transporter-specific [3H]dopamine uptake in RGS12-null ventral striatal
      synaptosomes was found to be increased. Decreased amphetamine-induced locomotor
      activity and increased [3H]WIN 35428 binding were recapitulated with an
      independent RGS12-null mouse strain. Thus, we propose that RGS12 regulates
      dopamine transporter expression and function in the ventral striatum, affecting
      amphetamine- and cocaine-induced increases in dopamine levels that specifically
      elicit acute hyperlocomotor responses.

PMID- 29364037
TI  - Comparisons of Segment Coordination: An Investigation of Vector Coding.
AB  - The development of a methodology to assess movement coordination has provided
      gait researchers a tool to assess movement organization. A challenge in analyzing
      movement coordination using vector coding lies within the inherent circularity of
      data garnered from this technique. Therefore, the purpose of this investigation
      was to determine if accurate group comparisons can be made with varying
      techniques of vector coding analyses. Thigh-shank coordination was analyzed using
      a modified vector coding technique on data from 2 groups of runners. Movement
      coordination was compared between groups using 3 techniques: (1) linear average
      completed with compressed data (0 degrees -180 degrees ) and noncompressed data
      (0 degrees -360 degrees ), (2) coordination phase binning analysis; and (3) a
      circular statistics analysis. Circular statistics (inferential) analysis provided
      a rigorous comparison of average movement coordination between groups. In
      addition, the binning analysis provided a metric for detecting even small
      differences in the time spent with a particular coordination pattern between
      groups. However, the linear analysis provided erroneous group comparisons.
      Furthermore, with compressed data, linear analysis led to misclassification of
      coordination patterns. While data compression may be attractive as a means of
      simplifying statistical analysis of inherently circular data, recommendations are
      to use circular statistics and binning methods on noncompressed data.

PMID- 29364038
TI  - Effects of Subsensory Noise and Fatigue on Knee Landing and Cross-over Cutting
      Biomechanics in Male Athletes.
AB  - The objective of this study was to examine the effects of subsensory noise and
      fatigue on knee biomechanics during the athletic task of landing followed by
      cross-over cutting. A total of 32 healthy male athletes participated in the
      study. They were evenly divided into 2 groups: no fatigue group and fatigue
      group. Fatigue was induced to the lower extremity by a repetitive squatting
      exercise in the fatigue group. Subsensory noise was generated by linear miniature
      vibrators bilaterally placed around the knee joints. During data collection, the
      participants were instructed to perform landing followed by cross-over cutting in
      both the subsensory on and off conditions. Dependent variables were selected to
      assess knee biomechanics in the phases of landing and cross-over cutting,
      separately. Results showed that fatigue resulted in larger knee flexion during
      landing and larger knee internal rotation during cross-over cutting. Subsensory
      noise was found to reduce knee rotation impulse during cross-over cutting. These
      findings suggest that cross-over cutting is more dangerous than landing in the
      fatigue condition, and subsensory noise may lead to changes in knee biomechanics
      consistent with reduced risk of anterior cruciate ligament injuries, but the
      changes may be task-specific.

PMID- 29364039
TI  - Neurophysiological correlate of emotional regulation in cognitive and motor
      deficits in Tourette's syndrome.
AB  - OBJECTIVES: The present study investigated the role of different emotions in the
      expression of cognitive and motor control abilities of children having Tourette's
      syndrome (TS) compared to healthy controls. METHODS: The electroencephalography
      activity of 33 children (mean age in final sample: TS (n = 10) = 10.5 +/- 2.3;
      control (n = 10) = 10.1 +/- 2.9) was recorded during a visual task consisting of
      four emotional face cues (anger, happiness, neutral and sadness) followed by a
      target in congruent or incongruent position with emotional cue. The participants
      were asked to indicate the target location. RESULTS: The TS patients showed a
      shorter latency of the P1 and N170 only for anger cues compared to controls. In
      addition, sLORETA results showed an increased activation in the left occipital
      area and a decreased activation in the left amygdala, temporal and cingulate for
      anger cues in TS patients. Coherently, TS patients showed a lower accuracy of
      response only with anger cue and severity of tics resulted correlated with the
      event-related potentials data and behavioural responses linked to anger cue.
      CONCLUSIONS: These results suggest that children with TS process emotions (in
      particular the anger) differently from the controls, and that its regulation
      seems to have an important role in the cognitive and motor deficits in TS.

PMID- 29364040
TI  - Comparison of Upper Trapezius and Infraspinatus Myofascial Trigger Point Therapy
      by Dry Needling in Overhead Athletes With Unilateral Shoulder Impingement
      Syndrome.
AB  - CONTEXT: Chronic musculoskeletal disorders in the shoulder joint are often
      associated with myofascial trigger points (MTrPs), particularly in the upper
      trapezius (UT) muscle. Dry needling (DN) is a treatment of choice for myofascial
      pain syndrome. However, local lesions and severe postneedle soreness sometimes
      hamper the direct application of DN in the UT. Therefore, finding an alternative
      point of treatment seems useful in this regard. OBJECTIVE: To compare the
      efficacy of UT versus infraspinatus (ISP) DN on pain and disability of subjects
      with shoulder pain. The authors hypothesized that ISP DN could be as effective as
      the direct application of DN in UT MTrP. DESIGN: Single-blind randomized clinical
      trial. SETTING: Sports medicine physical therapy clinic. PARTICIPANTS: A total of
      40 overhead athletes (age = 36 [16] y; 20 females and 20 males) with unilateral
      shoulder impingement syndrome were randomly assigned to the UT DN (n = 21) and
      ISP DN (n = 19) groups. INTERVENTION: An acupuncture needle was directly inserted
      into the trigger point of UT muscle in the UT DN group and of ISP muscle in the
      ISP DN group. DN was applied in 3 sessions (2-day interval between each sessions)
      for each group. MAIN OUTCOME MEASURES: Pain intensity (visual analog scale), pain
      pressure threshold, and disability in the arm, shoulder, and hand were assessed
      before and after the interventions. RESULTS: Pain and disability decreased
      significantly in both groups (P < .001) and pain pressure threshold increased
      significantly only in the ISP group (P = .02). However, none of the outcome
      measures showed a significant intergroup difference after treatments (P > .05).
      CONCLUSIONS: Application of DN for active MTrPs in the ISP can be as effective as
      direct DN of active MTrPs in the UT in improving pain and disability in athletes
      with shoulder pain, and may be preferred due to greater patient comfort in
      comparison with direct UT needling.

PMID- 29364041
TI  - Residual Force Enhancement in Humans: A Systematic Review.
AB  - A systematic literature search was conducted to review the evidence of residual
      force enhancement (RFE) in vivo human muscle. The search, adhered to the PRISMA
      statement, of CINAHL, EBSCO, Embase, MEDLINE, and Scopus (inception-July 2017)
      was conducted. Full-text English articles that assessed at least 1 measure of RFE
      in vivo voluntarily contracted human skeletal muscle were selected. The
      methodologies of included articles were assessed against the Downs and Black
      checklist. Twenty-four studies were included (N = 424). Pooled Downs and Black
      scores ranked "fair" ([Formula: see text] [2.26]). RFE was observed in all
      muscles tested. Joint range of motion varied from 15 degrees  to 60 degrees .
      Contraction intensities ranged from 10% to >95% maximum. Although transient force
      enhancement during the stretch phase may change with angular velocity, RFE in the
      subsequent isometric phase is independent of velocity. The magnitude of RFE was
      influenced by smaller stretch amplitudes and greatest at joint angles indicative
      of longer muscle lengths. Contraction and activation intensity influenced RFE,
      particularly during the initial isometric contraction phase of a poststretch
      isometric contraction. RFE resulted in increased torque production, reduced
      muscular activation, and enhanced torque production when the neuromuscular system
      is weakened seen in an aged population.

PMID- 29364042
TI  - Correlation among Y Balance Test-Lower Quarter Composite Scores, Hip
      Musculoskeletal Characteristics, and Pitching Kinematics in NCAA Division I
      Baseball Pitchers.
AB  - CONTEXT: Numerous studies have reported kinematic data on baseball pitchers using
      3D motion analysis, but no studies to date have correlated this data with
      clinical outcome measures. OBJECTIVE: To examine the relationship among Y Balance
      Test-Lower Quarter (YBT-LQ) composite scores, musculoskeletal characteristics of
      the hip and pitching kinematics in NCAA Division I baseball pitchers. DESIGN:
      Cross-sectional. SETTING: 3D motion analysis laboratory. PARTICIPANTS: 19 healthy
      male collegiate baseball pitchers. MAIN OUTCOME MEASURES: Internal and external
      hip passive range of motion (PROM); hip abduction strength; YBT-LQ composite
      scores; kinematic variables of the pitching motion. RESULTS: Stride length
      demonstrated a moderate positive correlation with dominant limb YBT-LQ composite
      score (r=0.524, p=0.018) and non-dominant limb YBT-LQ composite score (r=0.550,
      p=0.012), and a weak positive correlation with normalized time to maximal humerus
      velocity (r=0.458, p=0.043). Stride length had a moderate negative correlation
      with normalized time to maximal thorax velocity (r= -0.522, p=0.018) and dominant
      hip TRM (r= -0.660, p=0.002), and had a strong negative correlation with
      normalized time from SFC to maximal knee flexion (r= -0.722, p<0.001). Dominant
      limb YBT-LQ composite score had a weak negative correlation with hip abduction
      strength difference (r= -0.459, p=0.042) and normalized time to maximal thorax
      velocity (r= -0.468, p=0.037), as well as a moderate negative correlation with
      dominant hip TRM (r= -0.160, p=0.004). Non-dominant limb YBT-LQ composite score
      demonstrated a weak negative correlation with normalized time to maximal thorax
      velocity (r= -0.450, p=0.046) and had a moderate negative correlation with
      dominant hip TRM (r= -0.668, p=0.001). Hip abduction strength difference
      demonstrated a weak positive correlation with dominant hip TRM (r=0.482,
      p=0.032). Dominant hip TRM had a moderate positive correlation with normalized
      time to maximal thorax velocity (r=0.484, p=0.031). There were no other
      significant relationships between the remaining variables. CONCLUSIONS: YBT-LQ is
      a clinical measure which can be used to correlate with hip musculoskeletal
      characteristics and pitching kinematics in NCAA Division I pitchers.

PMID- 29364043
TI  - Lower Leg Morphology and Stretch-Shortening Cycle Performance of Dancers.
AB  - Greater levels of bone ultimate fracture load, bone stress-strain index, muscle
      cross-sectional area, and maximal voluntary isometric plantarflexion (MVIP)
      strength of the lower leg may be adaptations from chronic exposure to stretch
      shortening cycle (SSC) actions. Dancers, a population that habitually performs
      SSC movements primarily about the ankle joint, may serve as a novel population to
      gain broader understanding of SSC function. A total of 10 female collegiate
      dancers and 10 untrained controls underwent peripheral quantitative computed
      tomography scans of both lower legs and performed MVIPs, countermovement hops,
      and drop hops at 20, 30, and 40 cm on a custom-made inclined sled. Dancers had
      greater right and left ultimate fracture load values and significantly (P <= .05)
      greater left leg stress-strain index than controls. Dancers had significantly
      larger right and left muscle cross-sectional area and MVIP values and hopped
      significantly higher during all hopping conditions in comparison with controls.
      Average force-time and power-time curves revealed significantly greater relative
      force and power measurements during the concentric phase for all hopping
      conditions in dancers when compared with controls. This investigation provides
      evidence that dance may be a stimulus for positive muscle and bone adaptations,
      strength levels, and enhanced SSC capabilities.

PMID- 29364045
TI  - Isolated Infraspinatus Atrophy Secondary to Suprascapular Nerve Neuropathy
      Results in Altered Shoulder Muscles Activity.
AB  - CONTEXT: Isolated infraspinatus atrophy (IIA) is a common condition among
      overhead-activity athletes, which affects the hitting shoulder and is caused by
      suprascapular nerve injury. The loss of infraspinatus function could lead to
      altered activity of the glenohumeral and scapulothoracic muscles and compromise
      the optimal shoulder function. OBJECTIVE: To assess the surface electromyographic
      (sEMG) activity patterns, relationships, and response latencies of relevant
      shoulder girdle muscles in professional volleyball players with IIA and in
      healthy control players. DESIGN: Cross-sectional study. SETTING: Research
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-four male professional
      volleyball players (12 players with diagnosed IIA and 12 healthy players)
      recruited from local volleyball teams. INTERVENTION(S): sEMG activity of
      anterior, middle and posterior deltoid, upper, middle and lower trapezius, and
      serratus anterior was recorded and evaluated during a movement of shoulder
      abduction in the scapular plane, monitored with an optoelectronic motion capture
      system. MAIN OUTCOME MEASURE(S): sEMG activity, relationships, and response
      latencies of the selected muscles were analyzed with ANOVA models, to highlight
      statistical differences within and between groups. RESULTS: Athletes with IIA
      demonstrated significant higher deltoid and trapezius muscles activity, and lower
      serratus anterior activity, compared with the contralateral shoulder and with
      healthy athletes. The shoulder with IIA also showed a higher activity ratios
      between the upper trapezius and the other scapulothoracic muscles, in addition to
      anticipated activation of the upper trapezius and delayed activation of the
      serratus anterior, with regard to the onset of shoulder movement. CONCLUSIONS:
      The present study highlighted altered shoulder muscle activity levels,
      scapulothoracic muscles imbalances, and abnormal scapulothoracic recruitment
      patterns in the hitting shoulder of professional volleyball players with IIA,
      secondary to suprascapular nerve neuropathy. Such shoulder girdle muscles
      impairments may compromise the optimal scapulhoumeral rhythm and function,
      increasing the risk of acute and overuse shoulder injuries.

PMID- 29364046
TI  - Reliability of Hip Rotation Range of Motion in Supine and Seated Positions.
AB  - CONTEXT: Hip rotation range of motion (ROM) is commonly assessed in individuals
      with lower extremity or spine pathology. It remains unknown which hip rotation
      ROM testing position is most reliable. OBJECTIVE: To compare interrater and
      intrarater reliabilities between hip internal rotation (IR) and external rotation
      (ER) ROM in supine and seated positions. STUDY DESIGN: Controlled laboratory
      study. SETTING: University research laboratory. PARTICIPANTS: A total of 19
      participants (11 females and 8 males; age = 23.5 [1.2] y; height = 173.2 [8.6]
      cm; and mass = 69.2 [13.4] kg) without hip, knee, low back, or sacroiliac pain
      within the preceding 3 months or history of hip or low back surgery were
      recruited. INTERVENTIONS: Three testers obtained measures during 2 testing
      sessions. Passive supine and seated hip IR and ER ROM were performed with the hip
      and knee flexed to 90 degrees . MAIN OUTCOME MEASURES: The primary outcome
      measures were hip IR and ER ROM in supine and seated positions (in degrees).
      Interrater and intrarater reliabilities were calculated using intraclass
      correlation coefficients (ICCs). Minimal detectable change was calculated.
      Differences between supine and seated hip IR and ER ROM values were assessed
      using paired t tests (significance level was .05). RESULTS: Supine hip IR and ER
      ROM interrater and intrarater reliabilities were excellent (ICC = .75-.91).
      Seated hip IR ROM interrater and intrarater reliabilities were good (ICC = .64
      .71). Seated hip ER ROM interrater reliability was good (ICC = .65), and
      intrarater reliabilities were good to excellent (ICC = .65-.82). Minimal
      detectable change values for supine and seated hip IR and ER ROM ranged from 6.1
      degrees  to 8.6 degrees . There were significant differences between supine and
      seated positions for hip IR and ER ROM (41.6 degrees  vs 44.5 degrees ; P < .01
      and 53.0 degrees  vs 44.2 degrees ; P < .01, respectively). CONCLUSION: Supine
      hip rotation had higher interrater and intrarater reliabilities. Hip IR and ER
      ROM values differed significantly between supine and seated positions and should
      not be used interchangeably.

PMID- 29364044
TI  - Linc-RAM is required for FGF2 function in regulating myogenic cell
      differentiation.
AB  - Myogenic differentiation of skeletal muscle stem cells, also known satellite
      cells, is tightly orchestrated by extrinsic and intrinsic regulators. Basic
      fibroblast growth factor (FGF2) is well documented to be implicated in satellite
      cell self-renewal and differentiation by repressing MyoD. We recently identified
      a MyoD-regulated and skeletal muscle-specifically expressed long non-coding RNA
      Linc-RAM which enhances myogenic differentiation by facilitating MyoD/Baf60c/Brg1
      complex assembly. Herein, we investigated the transcriptional regulation and
      intracellular signaling pathway in mediating Linc-RAM gene expression during
      muscle cell differentiation. Firstly, we demonstrate Linc-RAM is negatively
      regulated by FGF2 via Ras/Raf/Mek/Erk signaling pathway in muscle cells.
      Overexpression of MyoD significantly attenuates repression of Linc-RAM promoter
      activities in C2C12 cells treated with FGF2. Knockout of MyoD abolishes FGF2
      mediated repression of Linc-RAM gene transcription in satellite cells sorted from
      skeletal muscle of MyoD-/-;Pax7-nGFP mice, suggesting inhibition of MyoD is
      required for FGF2-mediated expression of Linc-RAM. For the functional
      significance, we show that overexpression of Linc-RAM rescues FGF2-induced
      inhibition of C2C12 cell differentiation, indicating inhibition of Linc-RAM is
      required for FGF2-mediated suppression of myogenic differentiation. Consistently,
      we are able to further corroborate the requirement of Linc-RAM inhibition for
      FGF2-modulated repression of myogenic differentiation by using an ex vivo
      cultured single fiber system and satellite cells sorted from Linc-RAM-/-;Pax7
      nGFP knockout mice. Collectively, the present study not only reveals the
      intracellular signaling in FGF2-mediated Linc-RAM gene expression but also
      demonstrate the functional significance of Linc-RAM in FGF2-mediated muscle cell
      differentiation.

PMID- 29364048
TI  - Effect of Sex and Level of Activity on Lower Extremity Strength, Functional
      Performance and Limb Symmetry.
AB  - CONTEXT: Strength, functional performance and limb symmetry are common objective
      clinical assessments used by clinicians to guide safe return to physical activity
      following injury. Population-specific unilateral limb outcomes or estimates of
      limb symmetry of these assessments should be established. OBJECTIVE: To compare
      lower extremity strength, functional performance and limb symmetry in healthy
      participants based on sex and level of activity. DESIGN: Descriptive laboratory
      study Setting: Laboratory Participants: 117 healthy participants (72 males/45
      females, mass=73.67+/-13.60kg, height=1.76+/-0.12m, age=21.44+/-2.92 years)
      without history of injury within 6 months were included. INTERVENTIONS:
      Participants completed isokinetic concentric and isometric knee extension and
      flexion strength tasks at 90 degrees /s, 180 degrees /s and 90 degrees 
      respectively and four hop tasks(single, crossover, triple, 6m timed) during one
      session. Groups were separated by sex(male, female) and activity level(athlete,
      non-athlete). Participants rostered on National Collegiate Athletic
      Association(NCAA) Division I(DI) teams were considered athletes and non-NCAA DI
      healthy, uninjured participants were considered non-athletes. MAIN OUTCOME
      MEASURES: Limb Symmetry Index(LSI), maximal voluntary isometric contraction(MVIC,
      Nm/kg), peak torque(Nm/kg), average power(Nm/s), distance(m) and time hopped(s)
      were assessed. LSI was calculated by dividing the lower limb outcome by the
      higher limb outcome of the non-dominant or dominant limb. Group differences were
      assessed through Mann Whitney U tests and Cohen's d effect sizes for all
      comparisons. RESULTS: LSI differences did not exist between groups. Mean LSIs for
      all participants ranged between 83.52+/-12.54% and 96.16+/-3.82%. On average,
      males were stronger (Range d=0.63-1.54), hopped farther (Range d=1.52-1.63) and
      faster (Range d=1.67-1.68) than females. On average, some strength differences
      existed between athletes and non-athletes but athletes hopped farther (Range
      d=0.71-0.82) and faster (Range d=(0.87-0.88) than non-athletes. CONCLUSIONS:
      Unilateral limb strength and functional performance outcomes differ between sex
      and activity level, but not limb symmetry. These differences may be important for
      a clinician's understanding of normative values of common return to play
      assessment tasks.

PMID- 29364047
TI  - 27-Deoxyactein prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular
      damage in MC3T3-E1 osteoblastic cells.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental
      contaminant that exerts its toxicity through a variety of signaling mechanisms.
      The present study evaluated the effects of 27-deoxyactein, one of the major
      constituents isolated from Cimicifuga racemosa, on TCDD-induced toxicity in
      osteoblastic MC3T3-E1 cells. TCDD reduced cell survival, markedly increased
      apoptosis, and enhanced autophagy activity. However, pre-treatment with 27
      deoxyactein attenuated all TCDD-induced effects and significantly decreased
      intracellular calcium (Ca2+) concentrations, the collapse of the mitochondrial
      membrane potential (MMP), the level of reactive oxygen species (ROS), and
      cardiolipin peroxidation compared to the TCDD-treated controls. Additionally,
      TCDD-induced increases in the levels of aryl hydrocarbon receptor (AhR),
      cytochrome P450 1A1 (CYP1A1), and extracellular signal-regulated kinase (ERK)
      were significantly inhibited by 27-deoxyactein. The mRNA levels of superoxide
      dismutase (SOD), ERK1, and nuclear factor kappa B (NF-kappaB) were also
      effectively restored by pre-treatment with 27-deoxyactein. Furthermore, 27
      deoxyactein significantly increased the expressions of genes associated with
      osteoblast differentiation, including alkaline phosphatase (ALP), osteocalcin,
      bone sialoprotein (BSP), and osterix. Taken together, the present findings
      demonstrate the preventive effects of 27-deoxyactein on TCDD-induced damage in
      osteoblasts.

PMID- 29364049
TI  - Acute effects of hexavalent chromium on the performance and microbial community
      of activated sludge in aerobiotic reactors.
AB  - This study investigated the acute effects of hexavalent chromium (Cr(VI)) shock
      load at 2.5, 6 and 25 mg/L on the performance and bacterial community structures
      in aerobiotic activated sludge reactors. The results showed that eight-day Cr(VI)
      toxicity made the removal rates of COD and NH3-N to obviously decrease in all
      reactors. Furthermore, the higher the Cr(VI) concentration was, the more severe
      the influence on the whole system would be. The effect of Cr(VI) on NH3-N removal
      was more serious than that on COD and the function of nitrification was harder to
      recover. The specific oxygen uptake rate (SOUR) values dropped by 73%, 68% and
      31% at 2.5, 6 and 25 mg Cr(VI)/L, respectively. The data of SOUR showed that
      though the concentration of Cr(VI) was low, the whole respiratory activity of
      bacteria was much affected. The relative abundance change of genus between the
      initial stage and the last showed that the bacterial community structure changed
      significantly. Comparing with the initial stage, the phyla of Proteobacteria,
      Acidobacteria and Planctomycetes were markedly reduced at the end stage. The
      genera of Ferruginibacter, Coxiella and Rhodanobacter were also markedly reduced.
      Although the performance of activated sludge can be restored at the end, the
      whole respiratory activity of bacteria was still at a low level according to the
      data of SOUR.

PMID- 29364050
TI  - Estimates of Achilles Tendon Moment Arm Length at Different Ankle Joint Angles:
      Effect of Passive Moment.
AB  - The length of a muscle's moment arm can be estimated non-invasively using
      ultrasound, and the tendon excursion method. The main assumption with the tendon
      excursion method, however, is that the force acting on the tendon during passive
      rotation is constant. However, passive force changes through the range of motion,
      and moment arm is underestimated. We attempted to account for passive force on
      the measurement of Achilles tendon moment arm using the tendon excursion method
      in 8 male and female runners. Tendon excursion was measured using ultrasound
      while the ankle was passively rotated at 0.17 rad*s-1. Moment arm was calculated
      at 5 degrees  intervals as the ratio of tendon displacement to joint rotation
      from 70 degrees  to 115 degrees . Passive moment (MP) was measured by a
      dynamometer. The displacement attributable to MP was calculated by monitoring
      tendon displacement during a ramp isometric maximum contraction. MP was 5.7+/-2.1
      Nm at 70 degrees  and decreased exponentially from 70 degrees -90 degrees . 
      degrees . This resulted in MP-corrected moment arms that were significantly
      larger than uncorrected moment arms at joint angles where MP was present.
      Further, MP-corrected moment arms did not change with ankle angle, which was not
      the case for uncorrected moment arms.

PMID- 29364051
TI  - Prognostic Impact of Serum Albumin Concentration for Neurologically Favorable
      Outcome in Patients Treated with Targeted Temperature Management After Out-of
      Hospital Cardiac Arrest: A Multicenter Prospective Study.
AB  - To assess whether serum albumin concentration measured upon hospital arrival was
      useful as an early prognostic biomarker for neurologically favorable outcome in
      out-of-hospital cardiac arrest (OHCA) patients treated with target temperature
      management (TTM). This prospective, multicenter observational study (The CRITICAL
      Study) carried out between July 1, 2012 and December 31, 2014 in Osaka
      Prefecture, Japan involving 13 critical care medical centers (CCMCs) and one non
      CCMC with an emergency department. This study included patients >=18 years of age
      who underwent an OHCA, for whom resuscitation was attempted by Emergency Medical
      Services personnel and were then transported to participating institutions, and
      who were then treated with TTM. Based on the serum albumin concentration upon
      hospital arrival, involved patients were divided into four quartiles (Q1-Q4)
      defined as Q1 (<3.0 g/dL), Q2 (>=3.0, <3.4 g/dL), Q3 (>=3.4, <3.8 g/dL), and Q4
      (>=3.8 g/dL). The primary outcome of this study was 1-month survival with
      neurologically favorable outcome defined by cerebral performance category 1 or 2.
      During the study period, a total of 327 were eligible for our analysis. The
      overall proportion of neurologically favorable outcome was 33.0% (108/327). The
      Q4 group had the highest proportion of neurologically favorable outcome (52.5%
      [48/91]), followed by Q3 (34.5% [30/87]), Q2 (27.3% [21/77]), and Q1 (12.5%
      [9/72]). The multivariable logistic regression analysis demonstrated that the
      proportion of neurologically favorable outcome was significantly higher in the Q4
      group than that in the Q1 group (adjusted odds ratio 10.39; 95% confidence
      interval 3.36-32.17). The adjusted proportion of neurologically favorable outcome
      increased in a stepwise fashion across increasing quartiles (p < 0.001). In this
      study, higher serum albumin concentration upon hospital arrival had a positive
      association with neurologically favorable outcome after OHCA in a dose-dependent
      manner.

PMID- 29364052
TI  - Adsorption of Pb2+ from aqueous solutions using Fe-Mn binary oxides-loaded
      biochar: kinetics, isotherm and thermodynamic studies.
AB  - This study evaluated the removal of Pb2+ in aqueous solution using Fe-Mn binary
      oxides-loaded biochar (BFMs). The characteristics of BFM were obtained using a
      scanning electron microscopy, an energy dispersive spectrometer (EDS), Brunauer
      Emmett-Teller, a X-ray diffraction (XRD), and a X-ray photoelectron spectroscopy
      (XPS). The effects of pH, adsorbent dose, contact time, initial Pb2+
      concentration, and temperature in the batch sorption experiments were
      investigated. Adsorption was evaluated by adsorption kinetics, isotherm models,
      and thermodynamics. With the initial Pb2+ concentration of 200 mg/L, pH 4, and
      298.15 K, the optimum adsorption of BFM was obtained at a reaction time of 300
      min, adsorbent dose of 2 g/L, and maximum adsorption capacity of 113.715 mg/g.
      Furthermore, the kinetics was best fitted to the pseudo-second-order model,
      whereas the adsorption equilibrium was best described by the Langmuir isotherm
      model. This result indicated that Pb2+ was adsorbed onto BFM by chemical
      interactions through the monolayer. The adsorption was spontaneous (DeltaG < 0)
      and endothermic (DeltaH > 0).

PMID- 29364053
TI  - Modelling the mechanical strength development of treated fine sediments: a
      statistical approach.
AB  - Sediments valorization (recycling) has revealed limitations due to different
      restrains and practical difficulties. When it comes to different recovery
      methods, the possibility of valuing diverse types of sediments still needs to be
      defined. Using a statistical approach, the present study aims to quantitatively
      estimate the mechanical resistance of stabilized sediments. A database that
      included 22 fine sediments is selected and assembled from the literature. These
      sediments were treated with distinct types and quantities of additives (fillers
      and/or binders). The present study includes two parts. On one hand, using
      multivariate linear regression tool of XLstat software, an analytical model that
      highlights the effects of various parameters influencing the mechanical
      resistance of treated sediments after 28 days is obtained. This model showed that
      organic matter content and plasticity index are the most significant factors of
      sediments characteristics, while cement is the best mechanical strength booster.
      On the other hand, the evolution of treated sediments mechanical resistance over
      time is modelled by an exponential relationship using a least square regression
      method. Both models showed acceptable accuracies compared to a panel of selected
      experimental values.

PMID- 29364054
TI  - Optimization of UV/H2O2 and ozone wastewater treatment by the experimental design
      methodology.
AB  - The objective of this study was to optimize UV/H2O2 and ozonation systems by
      means of an experimental design using as a response the efficiency of the
      operational conditions to remove the methylene blue (MB) dye. Two classes of
      experimental planning were used: the Doehlert matrix (DM) and the central
      composite design (CCD). The most important variables for each process were
      hydrogen peroxide concentration, the ratio of illuminated volume/total volume of
      the reactor and recirculation flow rate for UV/H2O2, and ozone flow rate,
      consumed ozone and MB concentration for the ozonation. The DM was more efficient
      in optimizing the systems, since it used a smaller number of experiments and
      achieved similar results when compared to the CCD. After optimization, the
      disinfection efficiency of the systems was tested with secondary effluent
      evaluating the inactivation of microbiological indicators, Escherichia coli and
      total coliforms, using the optimized and the worst condition previously obtained
      with MB removal as response. The inactivation efficiencies in the optimum
      conditions were about 99%, allowing an efficient disinfection as well as the
      production of an effluent with quality to be reused according to specific
      legislations, while at the worse conditions, the inactivation did not reach
      standards for reuse.

PMID- 29364055
TI  - Location-based prospective memory.
AB  - This study explores location-based prospective memory. People often have to
      remember to do things when in a particular location, such as buying tissues the
      next time they are in the supermarket. For event cognition theory, location is
      important for structuring events. However, because event cognition has not been
      used to examine prospective memory, the question remains of how multiple events
      will influence prospective memory performance. In our experiments, people
      delivered messages from store to store in a virtual shopping mall as an ongoing
      task. The prospective tasks were to do certain activities in certain stores. For
      Experiment 1, each trial involved one prospective memory task to be done in a
      single location at one of three delays. The virtual environment and location cues
      were effective for prospective memory, and performance was unaffected by delay.
      For Experiment 2, each trial involved two prospective memory tasks, given in
      either one or two instruction locations, and to be done in either one or two
      store locations. There was improved performance when people received instructions
      from two locations and did both tasks in one location relative to other
      combinations. This demonstrates that location-based event structure influences
      how well people perform on prospective memory tasks.

PMID- 29364056
TI  - Positivity bias in past and future episodic thinking: Relationship with anxiety,
      depression, and retrieval-induced forgetting.
AB  - Positivity biases in autobiographical memory and episodic future thinking are
      considered important in mental wellbeing and are reduced in anxiety and
      depression. The inhibitory processes underlying retrieval-induced forgetting
      (RIF) have been proposed to contribute to these biases. This investigation found
      reduced positivity in past and future thinking to be associated with reduced
      memory specificity alongside greater levels of anxiety, depression, and
      rumination. Most notably, however, RIF was found to significantly predict memory
      valence. This indicates that RIF may be important in maintaining such biases,
      facilitating the forgetting of negative memories when a positive item is actively
      retrieved.

PMID- 29364057
TI  - Gas-phase elemental mercury removal using ammonium chloride impregnated sargassum
      chars.
AB  - In this article, pyrolyzed bio-chars derived from a kind of macroalgae,
      sargassum, were modified by ammonium chloride (NH4Cl) impregnation, and were
      applied to remove Hg0 from flue gas. The characteristics of sorbents were
      investigated by the Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy,
      scanning electron microscopy and ultimate and proximate analysis. The key
      parameters (e.g. loading value, reaction temperature and concentration of O2, NO,
      SO2 and water vapor), kinetics analysis and reaction mechanism of Hg0 removal
      were investigated. The results show that increasing loading value, reaction
      temperature, O2 concentration and NO concentration enhance Hg0 removal. The
      increase in SO2 concentration or water vapor concentration has a dual effect on
      Hg0 removal. The C-Cl groups and C=O groups play an important role in the process
      of Hg0 removal. The Hg0 removal process of modified samples meets the pseudo
      second-order kinetic model.

PMID- 29364058
TI  - Landfill leachate treatment by coagulation/flocculation combined with
      microelectrolysis-Fenton processes.
AB  - Landfill leachate was pretreated by chemical flocculation with polyaluminum
      chloride (PAC) as a flocculant, and subsequently purified by the
      microelectrolysis-Fenton (MEF) process. Response surface methodology was employed
      to optimize the MEF process, and the optimal conditions were initial pH 3.20,
      H2O2 concentration 3.57 g/L, and Fe-C dosage 104.52 g/L. The PAC coagulation
      combined with MEF processes obtained a superior decontamination performance, and
      the predicted chemical oxygen demand (COD) and humic acids (HA) removal were
      respectively 90.27% and 93.79%. The strong fluorescence peak at 425 nm and the
      trapping experiment showed that [Formula: see text] was generated during MEF,
      which had a strong oxidation ability to degrade organic recalcitrant pollutants.
      The ultraviolet-visible spectra and three-dimensional excitation-emission
      matrices spectra (3D-EEMs) indicated that PAC coagulation could preferentially
      remove protein-like substances, while the MEF process was effective in
      destructing organic recalcitrant pollutants, especially humic-like and fulvic
      like substances.

PMID- 29364059
TI  - Controlled synthesis of Bi2O3/TiO2 catalysts with mixed alcohols for the
      photocatalytic oxidation of HCHO.
AB  - Bi2O3/TiO2 photocatalysts were prepared by a hydrothermal method. The
      photocatalysts were applied to the catalytic oxidation of indoor formaldehyde
      vapors under irradiation by an light-emitting diode energy-saving lamp. The
      characterization methods including Brunauer-Emmett-Teller, X-ay diffraction, UV
      vis spectra, scanning electron microscopy, Transmission electron microscopy and X
      ray photoelectron spectroscopy analysis were used to investigate the crystalline
      structure, morphology, specific surface area and porosity. The effects of the
      preparation conditions, including the type of alcohols, molar ratio and
      calcination temperature, on the morphology, structure and crystalline phase of
      the catalyst were also investigated. The results reveal that the morphology could
      be controlled by using different types of alcohols, especially mixed alcohols.
      The morphology played a key role in determining the photodegradation efficiency
      of formaldehyde. According to the experimental results, the Bi2O3/TiO2 catalysts
      with amorphous particles showed the highest activity. The presence of anatase
      TiO2 and Bi4(TiO4)3 with a heterojunction structure was the main reason for the
      high activity, and they were beneficial for increasing the separation of the
      photogenerated electrons and holes and decreasing their recombination through
      electron transformations.

PMID- 29364061
TI  - On the perceptual aesthetics of interactive objects.
AB  - This study examined the aesthetics of interactive objects (IOs), which are three
      dimensional physical artefacts that exhibit autonomous behaviour when handled.
      The aim of the research was threefold: first, to investigate whether aesthetic
      preference for distinctive objects' structures emerges in compound stimulation;
      second, to explore whether there exists aesthetic preference for distinctive
      objects' behaviours; and, finally, to test whether there exists aesthetic
      preference for specific combinations of objects' structures and behaviours. The
      following variables were systematically manipulated: (a) IOs' contour (rounded vs
      angular), (b) IOs' size (small vs large), (c) IOs' surface texture (rough vs
      smooth), and (d) IOs' behaviour (lighting, sounding, vibrating, and quiescent).
      Results show that behaviour was the dominant factor: it influenced aesthetics
      more than any other characteristic; vibrating IOs were preferred over lighting
      and sounding IOs, supporting the importance of haptic processing in aesthetics.
      Results did not confirm the size and smoothness effects previously reported in
      vision and touch, respectively, which suggests that the aesthetic preference that
      emerges in isolated conditions may be different in compound stimulation. Results
      corroborate the smooth curvature effect. We suggest that behavior may be an
      aesthetic primitive.

PMID- 29364063
TI  - Impact of carbohydrate mouth rinsing on time to exhaustion during Ramadan: A
      randomized controlled trial in Jordanian men.
AB  - Mouth rinsing using a carbohydrate (CHO) solution has been suggested to improve
      physical performance in fasting participants. This study examined the effects of
      CHO mouth rinsing during Ramadan fasting on running time to exhaustion and on
      peak treadmill speed (Vpeak). In a counterbalanced crossover design, 18 sub-elite
      male runners (Age: 21 +/- 2 years, Weight: 68.1 +/- 5.7 kg, VO2max: 55.4 +/- 4.8
      ml/kg/min) who observed Ramadan completed a familiarization trial and three
      experimental trials. The three trials included rinsing and expectorating a 25 mL
      bolus of either a 7.5% sucrose solution (CHO), a flavour and taste matched
      placebo solution (PLA) for 10 s, or no rinse (CON). The treatments were performed
      prior to an incremental treadmill test to exhaustion. Three-day dietary and
      exercise records were obtained on two occasions and analysed. Anthropometric
      characteristics were obtained and recorded for all participants. A main effect
      for mouth rinse on peak velocity (Vpeak) (CHO: 17.6 +/- 1.5 km/h; PLA: 17.1 +/-
      1.4 km/h; CON: 16.7 +/- 1.2 km/h; P < .001, etap2 = 0.49) and time to exhaustion
      (CHO: 1282.0 +/- 121.3 s; PLA: 1258.1 +/- 113.4 s; CON: 1228.7 +/- 98.5 s; P =
      .002, etap2 = 0.41) was detected, with CHO significantly higher than PLA (P <
      .05) and CON (P < .05). Oxygen consumption, heart rate, respiratory exchange
      ratio, and rating of perceived exertion were not significantly different between
      treatments or trials (P > .05). Energy availability from dietary analysis, body
      weight, and fat-free mass did not change during the last two weeks of Ramadan (P
      > .05). This study concludes that carbohydrate mouth rinsing improves running
      time to exhaustion and peak treadmill speed under Ramadan fasting conditions.

PMID- 29364062
TI  - Water-filled training tubes increase core muscle activation and somatosensory
      control of balance during squat.
AB  - This study examined trunk muscle activation, balance and proprioception while
      squatting with a water-filled training tube (WT) and a traditional barbell (BB),
      with either closed (CE) or open eyes (OE). Eighteen male elite Gaelic footballers
      performed an isometric squat under the following conditions: BB-OE, BB-CE, WT-OE
      and WT-CE. The activity of rectus abdominis (RA), external oblique (EO) and
      multifidus (MF) was measured using electromyography, along with sway of the
      centre of pressure (CoP) using a force platform. Only the EO and the MF muscles
      exhibited an increased activity with WT (p < 0.01). In the medio-lateral
      direction both the velocity and range of the CoP increased significantly with WT
      (p < 0.01). Interestingly, the range of the CoP for the WT-CE condition was
      significantly lower than WT-OE (p < 0.05, d = 0.44), whilst the velocity of the
      CoP was marginally reduced (d = 0.29). WT elicited a greater level core muscle
      activation and created a greater challenge to postural stability when compared to
      a BB. It appears that WT does not benefit from vision but emphasises the
      somatosensory control of balance. The use of WT may be beneficial in those sports
      requiring development of somatosensory/proprioceptive contribution to balance
      control.

PMID- 29364064
TI  - Uranium oxide catalysts: environmental applications for treatment of chlorinated
      organic waste from nuclear industry.
AB  - Huge amounts of nuclear waste, including depleted uranium, significantly
      contribute to the adverse environmental situation throughout the world. An
      approach to the effective use of uranium oxides in catalysts for the deep
      oxidation of chlorine-containing hydrocarbons is suggested. Investigation of the
      catalytic activity of the synthesized supported uranium oxide catalysts doped
      with Cr, Mn and Co transition metals in the chlorobenzene oxidation showed that
      these catalysts are comparable with conventional commercial ones. Physicochemical
      properties of the catalysts were studied by X-ray diffraction, temperature
      programmed reduction with hydrogen (H2-TPR), and Fourier transform infrared
      spectroscopy. The higher activity of Mn- and Co-containing uranium oxide
      catalysts in the H2-TPR and oxidation of chlorobenzene in comparison with non
      uranium catalysts may be related to the formation of a new disperse phase
      represented by uranates. The study of chlorobenzene adsorption revealed that the
      surface oxygen is involved in the catalytic process.

PMID- 29364065
TI  - Validation of Electronic Activity Monitor Devices During Treadmill Walking.
AB  - INTRODUCTION: The purpose of this study was to assess the validity of the step
      count measurement of commercial electronic activity monitor devices. Two popular
      models, Fitbit Charge HR and Mi Band 2, were selected for treadmill walking in a
      single session. MATERIALS AND METHODS: Thirty healthy volunteers walked at five
      predetermined speeds (0.90, 1.12, 1.33, 1.54, and 1.78 m/s) on a treadmill with
      both Fitbit Charge HR and Mi Band 2 worn on their dominant hand's wrist.
      Observers counted the steps, with the aid of taped video, which was taken as the
      criterion measure for steps. The validity of the electronic activity devices was
      assessed by (1) Paired sample t test with the criterion measures and (2)
      Pearson's correlation coefficients and the corresponding p-values were calculated
      to compare the output of devices with manual step count. In addition, Bland
      Altman plots were constructed to visually inspect the data and to assess
      agreement with the criterion measures. RESULTS: There were no significant
      differences in step measurement between Fitbit Charge HR and Mi Band 2 with the
      criterion measures. Besides, there was a very strong agreement between step count
      measurements obtained using the Fitbit Charge HR (r = 0.99) and the Mi Band 2 (r
      = 0.99), at five predetermined speeds while comparing with the observed step
      counts. CONCLUSION: Both Fitbit Charge HR and Mi Band 2 provided accurate step
      count measurement in the treadmill walking test.

PMID- 29364066
TI  - Physical Training and Upper Limb Strength of people with paraplegia: A Systematic
      Review.
AB  - CONTEXT: Physical training improves the strength of upper limbs, contributing
      directly to the performance of activities of daily life (ADL), confirming one
      more time that the strengthened muscle is imperative for a rapid rehabilitation.
      OBJECTIVE: investigate the scientific implications of the impact of physical
      training on the strength of the upper limbs of people with paraplegias. EVIDENCE
      ACQUISITION: the search strategy with truncations and Boolean operator was
      defined as: (spinal cord inju* OR traumatic myelopat* OR paraplegi*) AND
      (physical exercise OR strength training OR resisted training) AND (upper limb* OR
      arm OR armrest), for all of the databases. Were included experimental and quasi
      experimental studies, published in the English language and with the complete
      text available, with at least one physical exercise that worked with the strength
      of the upper limbs. Two independent evaluators extracted from each article data
      on study characteristics (publishing year, country of origin and study design),
      of the subjects (gender and age), and of the disability (Level of Lesion and
      Cause). EVIDENCE SYNTHESIS: Seven articles were included in the systematic
      revision. The procedure used the most for measuring the maximum strength was the
      1 Repetition Maximum test, followed by isokinetic dynamometer and Quantitative
      Muscle Testing System (QMT). Furthermore, the variables most commonly associated
      in the included studies were pain in the shoulder, cardiorespiratory capacity and
      functionality, respectively. The results showed that all of the variables
      improved because of the training. CONCLUSIONS: The training improved the
      strength, the functionality and reduces the pain on the shoulder of the people
      with paraplegia.

PMID- 29364067
TI  - Effect of experimental muscle pain on the acquisition and retention of locomotor
      adaptation: different motor strategies for a similar performance.
AB  - As individuals with musculoskeletal disorders often experience motor impairments,
      contemporary rehabilitation relies heavily on the use of motor learning
      principles. However, motor impairments are often associated with pain. Although
      there is substantial evidence that muscle pain interferes with motor control,
      much less is known on its impact on motor learning. The objective of the present
      study was to assess the effects of muscle pain on locomotor learning. Two groups
      (Pain and Control) of healthy participants performed a locomotor adaptation task
      (robotized ankle-foot orthosis perturbing ankle movements during swing) on two
      consecutive days. On day 1 (acquisition), hypertonic saline was injected in the
      tibialis anterior (TA) muscle of the Pain group participants, while Control group
      participants were pain free. All participants were pain free on day 2
      (retention). Changes in movement errors caused by the perturbation were assessed
      as an indicator of motor performance. Detailed analysis of kinematic and
      electromyographic data provided information about motor strategies. No between
      group differences were observed on motor performance measured during the
      acquisition and retention phases. However, Pain group participants had a residual
      movement error later in the swing phase and smaller early TA activation than
      Control group participants, thereby suggesting a reduction in the use of
      anticipatory motor strategies to overcome the perturbation. Muscle pain did not
      interfere with global motor performance during locomotor adaptation. The
      different motor strategies used in the presence of muscle pain may reflect a
      diminished ability to anticipate the consequences of a perturbation. NEW &
      NOTEWORTHY This study shows that experimental muscle pain does not influence
      global motor performance during the acquisition or next-day retention phases of
      locomotor learning. This contrasts with previous results obtained with cutaneous
      pain, emphasizing the risk of directly extrapolating from one pain modality to
      another. Muscle pain affected motor strategies used when performing the task,
      however: it reduced the ability to use increased feedforward control to overcome
      the force field.

PMID- 29364068
TI  - Methods for chair restraint and training of the common marmoset on oculomotor
      tasks.
AB  - The oculomotor system is the most thoroughly understood sensorimotor system in
      the brain, due in large part to electrophysiological studies carried out in
      macaque monkeys trained to perform oculomotor tasks. A disadvantage of the
      macaque model is that many cortical oculomotor areas of interest lie within
      sulci, making high-density array and laminar recordings impractical. Many
      techniques of molecular biology developed in rodents, such as optogenetic
      manipulation of neuronal subtypes, are also limited in this species. The common
      marmoset ( Callithrix jacchus) possesses a smooth cortex, allowing easy access to
      frontoparietal oculomotor areas, and may bridge the gap between systems
      neuroscience in macaques and molecular techniques. Techniques for restraint,
      training, and neural recording in these animals have been well developed in
      auditory neuroscience. Those for oculomotor neuroscience, however, remain at a
      relatively early stage. In this article we provide details of a custom-designed
      restraint chair for marmosets, a combination head restraint/recording chamber
      allowing access to cortical oculomotor areas and providing stability suitable for
      eye movement and neural recordings, as well as a training protocol for oculomotor
      tasks. We additionally report the results of a psychophysical study in marmosets
      trained to perform a saccade task using these methods, showing that, as in rhesus
      and humans, marmosets exhibit a "gap effect," a decrease in reaction time when
      the fixation stimulus is removed before the onset of a visual saccade target.
      These results are the first evidence of this effect in marmosets and support the
      common marmoset model for neurophysiological investigations of oculomotor
      control. NEW & NOTEWORTHY The ability to carry out neuronal recordings in
      behaving primates has provided a wealth of information regarding the neural
      circuits underlying the control of eye movements. Such studies require restraint
      of the animal within a primate chair, head fixation, methods of acclimating the
      animals to this restraint, and the use of operant conditioning methods for
      training on oculomotor tasks. In contrast to the macaque model, relatively few
      studies have reported in detail methods for use in the common marmoset. In this
      report we detail custom-designed equipment and methods by which we have used to
      successfully train head-restrained marmosets to perform basic oculomotor tasks.

PMID- 29364069
TI  - The signature of undetected change: an exploratory electrotomographic
      investigation of gradual change blindness.
AB  - Neuroimaging-based investigations of change blindness, a phenomenon in which
      seemingly obvious changes in visual scenes fail to be detected, have
      significantly advanced our understanding of visual awareness. The vast majority
      of prior investigations, however, utilize paradigms involving visual disruptions
      (e.g., intervening blank screens, saccadic movements, "mudsplashes"), making it
      difficult to isolate neural responses toward visual changes cleanly. To address
      this issue in this present study, high-density EEG data (256 channel) were
      collected from 25 participants using a paradigm in which visual changes were
      progressively introduced into detailed real-world scenes without the use of
      visual disruption. Oscillatory activity associated with undetected changes was
      contrasted with activity linked to their absence using standardized low
      resolution brain electromagnetic tomography (sLORETA). Although an insufficient
      number of detections were present to allow for analysis of actual change
      detection, increased beta-2 activity in the right inferior parietal lobule
      (rIPL), a region repeatedly associated with change blindness in disruption
      paradigms, followed by increased theta activity in the right superior temporal
      gyrus (rSTG) was noted in undetected visual change responses relative to the
      absence of change. We propose the rIPL beta-2 activity to be associated with
      orienting attention toward visual changes, with the subsequent rise in rSTG theta
      activity being potentially linked with updating preconscious perceptual memory
      representations. NEW & NOTEWORTHY This study represents the first neuroimaging
      based investigation of gradual change blindness, a visual phenomenon that has
      significant potential to shed light on the processes underlying visual detection
      and conscious perception. The use of gradual change materials is reflective of
      real-world visual phenomena and allows for cleaner isolation of signals
      associated with the neural registration of change relative to the use of abrupt
      change transients.

PMID- 29364070
TI  - Swimming rhythm generation in the caudal hindbrain of the lamprey.
AB  - The spinal cord has been well established as the site of generation of the
      locomotor rhythm in vertebrates, but studies have suggested that the caudal
      hindbrain in larval fish and amphibians can also generate locomotor rhythms.
      Here, we investigated whether the caudal hindbrain of the adult lamprey (
      Petromyzon marinus and Ichthyomyzon unicuspis) has the ability to generate the
      swimming rhythm. The hindbrain-spinal cord transition zone of the lamprey
      contains a bilateral column of somatic motoneurons that project via the spino
      occipital (S-O) nerves to several muscles of the head. In the brainstem-spinal
      cord-muscle preparation, these muscles were found to burst and contract
      rhythmically with a left-right alternation when swimming activity was evoked with
      a brief electrical stimulation of the spinal cord. In the absence of muscles, the
      isolated brainstem-spinal cord preparation also produced alternating left-right
      bursts in S-O nerves (i.e., fictive swimming), and the S-O nerve bursts preceded
      the bursts occurring in the first ipsilateral spinal ventral root. After physical
      isolation of the S-O region using transverse cuts of the nervous system, the S-O
      nerves still exhibited rhythmic bursting with left-right alternation when
      glutamate was added to the bathing solution. We conclude that the S-O region of
      the lamprey contains a swimming rhythm generator that produces the leading motor
      nerve bursts of each swimming cycle, which then propagate down the spinal cord to
      produce forward swimming. The S-O region of the hindbrain-spinal cord transition
      zone may play a role in regulating speed, turning, and head orientation during
      swimming in lamprey. NEW & NOTEWORTHY Although it has been well established that
      locomotor rhythm generation occurs in the spinal cord of vertebrates, it was
      unknown whether the hindbrain of the adult vertebrate nervous system can also
      generate the locomotor rhythm. Here, we show that the isolated hindbrain-spinal
      cord transition zone of adult lamprey can generate the swimming rhythm. In
      addition, the swimming bursts of the hindbrain lead the bursts occurring in the
      first segment of the spinal cord.

PMID- 29364071
TI  - Regulation of Eag by Ca2+/calmodulin controls presynaptic excitability in
      Drosophila.
AB  - Drosophila ether-a-go-go ( eag) is the founding member of a large family of
      voltage-gated K+ channels, the KCNH family, which includes Kv10, 11, and 12.
      Concurrent binding of calcium/calmodulin (Ca2+/CaM) to NH2- and COOH-terminal
      sites inhibits mammalian EAG1 channels at submicromolar Ca2+ concentrations,
      likely by causing pore constriction. Although the Drosophila EAG channel was
      believed to be Ca2+-insensitive (Schonherr R, Lober K, Heinemann SH. EMBO J 19:
      3263-3271, 2000.), both the NH2- and COOH-terminal sites are conserved. In this
      study we show that Drosophila EAG is inhibited by high Ca2+ concentrations that
      are only present at plasma membrane Ca2+ channel microdomains. To test the role
      of this regulation in vivo, we engineered mutations that block CaM-binding to the
      major COOH-terminal site of the endogenous eag locus, disrupting Ca2+-dependent
      inhibition. eag CaMBD mutants have reduced evoked release from larval motor
      neuron presynaptic terminals and show decreased Ca2+ influx in stimulated adult
      projection neuron presynaptic terminals, consistent with an increase in K+
      conductance. These results are predicted by a conductance-based multicompartment
      model of the presynaptic terminal in which some fraction of EAG is localized to
      the Ca2+ channel microdomains that control neurotransmitter release. The
      reduction of release in the larval neuromuscular junction drives a compensatory
      increase in motor neuron somatic excitability. This misregulation of synaptic and
      somatic excitability has consequences for systems-level processes and leads to
      defects in associative memory formation in adults. NEW & NOTEWORTHY Regulation of
      excitability is critical to tuning the nervous system for complex behaviors. We
      demonstrate in this article that the EAG family of voltage-gated K+ channels
      exhibit conserved gating by Ca2+/CaM. Disruption of this inhibition in Drosophila
      results in decreased evoked neurotransmitter release due to truncated Ca2+ influx
      in presynaptic terminals. In adults, disrupted Ca2+ dynamics cripples memory
      formation. These data demonstrate that the biophysical details of channels have
      important implications for cell function and behavior.

PMID- 29364072
TI  - The antihelminthic moxidectin enhances tonic GABA currents in rodent hippocampal
      pyramidal neurons.
AB  - Macrocyclic lactones (MLs) are commonly used treatments for parasitic worm and
      insect infections in humans, livestock, and companion animals. MLs target the
      invertebrate glutamate-activated chloride channel that is not present in
      vertebrates. MLs are not entirely inert in vertebrates, though; they have been
      reported to have activity in heterologous expression systems consisting of ligand
      gated ion channels that are present in the mammalian central nervous system
      (CNS). However, these compounds are typically not able to reach significant
      concentrations in the CNS because of the activity of the blood-brain barrier P
      glycoprotein extrusion system. Despite this, these compounds are able to reach
      low levels in the CNS that may be useful in the design of novel "designer" ligand
      receptor systems that can be used to directly investigate neuronal control of
      behavior in mammals and have potential for use in treating human neurological
      diseases. To determine whether MLs might affect neurons in intact brains, we
      investigated the activity of the ML moxidectin (MOX) at native GABA receptors.
      Specifically, we recorded tonic and phasic miniature inhibitory postsynaptic
      currents (mIPSCs) in ex vivo brain slices. Our data show that MOX potentiated
      tonic GABA currents in a dose-dependent manner but had no concomitant effects on
      phasic GABA currents (i.e., MOX had no effect on the amplitude, frequency, or
      decay kinetics of mIPSCs). These studies indicate that behavioral experiments
      that implement a ML-based novel ligand-receptor system should take care to
      control for potential effects of the ML on native tonic GABA receptors. NEW &
      NOTEWORTHY We have identified a novel mechanism of action in the mammalian
      central nervous system for the antihelminthic moxidectin, commonly prescribed to
      animals worldwide and currently being evaluated for use in humans. Specifically,
      moxidectin applied to rodent brain slices selectively enhanced the tonic GABA
      conductance of hippocampal pyramidal neurons.

PMID- 29364074
TI  - Non-gait-specific intervention for the rehabilitation of walking after SCI: role
      of the arms.
AB  - Arm movements modulate leg activity and improve gait efficiency; however, current
      rehabilitation interventions focus on improving walking through gait-specific
      training and do not actively involve the arms. The goal of this project was to
      assess the effect of a rehabilitation strategy involving simultaneous arm and leg
      cycling on improving walking after incomplete spinal cord injury (iSCI). We
      investigated the effect of 1) non-gait-specific training and 2) active arm
      involvement during training on changes in over ground walking capacity.
      Participants with iSCI were assigned to simultaneous arm-leg cycling (A&L) or
      legs only cycling (Leg) training paradigms, and cycling movements were assisted
      with electrical stimulation. Overground walking speed significantly increased by
      0.092 +/- 0.022 m/s in the Leg group and 0.27 +/- 0.072m/s in the A&L group after
      training. Whereas the increases in the Leg group were similar to those seen after
      current locomotor training strategies, increases in the A&L group were
      significantly larger than those in the Leg group. Walking distance also
      significantly increased by 32.12 +/- 8.74 m in the Leg and 91.58 +/- 36.24 m in
      the A&L group. Muscle strength, sensation, and balance improved in both groups;
      however, the A&L group had significant improvements in most gait measures and had
      more regulated joint kinematics and muscle activity after training compared with
      the Leg group. We conclude that electrical stimulation-assisted cycling training
      can produce significant improvements in walking after SCI. Furthermore, active
      arm involvement during training can produce greater improvements in walking
      performance. This strategy may also be effective in people with other neural
      disorders or diseases. NEW & NOTEWORTHY This work challenges concepts of task
      specific training for the rehabilitation of walking and encourages coordinated
      training of the arms and legs after spinal cord injury. Cycling of the legs
      produced significant improvements in walking that were similar in magnitude to
      those reported with gait-specific training. Moreover, active engagement of the
      arms simultaneously with the legs generated nearly double the improvements
      obtained by leg training only. The cervico-lumbar networks are critical for the
      improvement of walking.

PMID- 29364075
TI  - Psychoanalysis and the Challenges of Disciplinary Exportation: Notes from the
      African "Periphery" on the Method/Theory Distinction.
AB  - This paper briefly reports on the current expansion of opportunities for clinical
      education in psychoanalysis in southern Africa, various regions of Asia, and
      Iran. It is a preliminary reconsideration of whether the disciplinary export of
      psychoanalysis is another egregious exercise in neo-colonialism, as contrasted
      with its possibly liberatory significance. The author argues that much of the
      discussion around the universality of many theoretical propositions needs to be
      reformulated. For example, the controversies over the Oedipus complex have
      typically been articulated in terms of the effects of specific social
      arrangements, familial structures, and styles of maternal and paternal
      functioning, rather than in terms of the universal-but with much cultural
      variation in its implementation-incest taboo. It is argued that dissemination of
      the psychoanalytic method (and the four coordinates that follow from it) may be
      desirable, but in ways the export of the hermeneutic assumptions of certain
      theoretical models is not.

PMID- 29364073
TI  - Amplitude modulation coding in awake mice and squirrel monkeys.
AB  - Both mice and primates are used to model the human auditory system. The primate
      order possesses unique cortical specializations that govern auditory processing.
      Given the power of molecular and genetic tools available in the mouse model, it
      is essential to understand the similarities and differences in auditory cortical
      processing between mice and primates. To address this issue, we directly compared
      temporal encoding properties of neurons in the auditory cortex of awake mice and
      awake squirrel monkeys (SQMs). Stimuli were drawn from a sinusoidal amplitude
      modulation (SAM) paradigm, which has been used previously both to characterize
      temporal precision and to model the envelopes of natural sounds. Neural responses
      were analyzed with linear template-based decoders. In both species, spike timing
      information supported better modulation frequency discrimination than rate
      information, and multiunit responses generally supported more accurate
      discrimination than single-unit responses from the same site. However, cortical
      responses in SQMs supported better discrimination overall, reflecting superior
      temporal precision and greater rate modulation relative to the spontaneous
      baseline and suggesting that spiking activity in mouse cortex was less strictly
      regimented by incoming acoustic information. The quantitative differences we
      observed between SQM and mouse cortex support the idea that SQMs offer advantages
      for modeling precise responses to fast envelope dynamics relevant to human
      auditory processing. Nevertheless, our results indicate that cortical temporal
      processing is qualitatively similar in mice and SQMs and thus recommend the mouse
      model for mechanistic questions, such as development and circuit function, where
      its substantial methodological advantages can be exploited. NEW & NOTEWORTHY To
      understand the advantages of different model organisms, it is necessary to
      directly compare sensory responses across species. Contrasting temporal
      processing in auditory cortex of awake squirrel monkeys and mice, with
      parametrically matched amplitude-modulated tone stimuli, reveals a similar role
      of timing information in stimulus encoding. However, disparities in response
      precision and strength suggest that anatomical and biophysical differences
      between squirrel monkeys and mice produce quantitative but not qualitative
      differences in processing strategy.

PMID- 29364076
TI  - Studium and Punctum in Psychoanalytic Writing: Reading Case Studies Through
      Roland Barthes.
AB  - This paper focuses on the link between Roland Barthes's reflection on photography
      and the essential characteristics of psychoanalytic case studies. The case study,
      like the photograph, seeks to take hold of something nearly intangible. It
      attempts to capture in time, space, and language something whose dynamic presence
      remains elusive. The attempt to capture this object often strips it of its
      essence. Case studies may be accurate on their face while giving us the
      unpleasant sense that they have "deadened" their object in the process. This
      paper attempts to clarify what is dropped from the picture that the
      psychoanalytic writing is trying to take. The relation between the "cultural
      context" (the Studium) and the freedom to puncture and undermine this context in
      psychoanalytic writing is discussed through a fresh reading of Georges Perec's
      "W, or the Memory of Childhood" and through clinical vignettes by Ronald Britton
      and Michael Eigen.

PMID- 29364077
TI  - Einstein, Time, and the Unconscious.
AB  - This paper discusses how we interpret and experience time and how such
      experiences affect our understanding of the topographical as well as the
      structural models. Following the thought of both ancient Hindu teachings (the
      Upanishads) and contemporary findings from quantum mechanics, the paper frames
      the discussion within a unitary experience of both mind and everyday experience.
      The function and role of clinical interpretations are also discussed. Following
      the tradition articulated in Roy Schaffer's action language model as well as
      insights from existentialism, the paper offers a deeper appreciation of
      individual agency and its role in self-understanding and personal growth.

PMID- 29364078
TI  - Equivalence in Freud's Primary Process.
AB  - Freud's concept of the primary process, when confined to the selection of objects
      for the formation of dreams or symptoms, depends strongly on the concept of
      association, which in turn depends strongly on the logic of pars pro toto. An
      examination of how Freud saw the primary process selecting objects leads to the
      identification of an equivalence relationship as governing his model. This
      results in a logical understanding of how the primary process works in forming
      associations and choosing candidate objects for dreams and symptoms. The
      relationship of this result to the work of Matte Blanco is also discussed, and
      the insights of this paper are applied to defining Freud's concept of a complex.

PMID- 29364080
TI  - From Continuity to Contiguity: A Response to the Fraught Temporality of Gender.
AB  - This paper examines current psychoanalytic engagements with the use of hormone
      blockers in transsexual children and the underlying premises concerning our
      understanding of the child's process of coming into his or her gendered self.
      Rather than taking sides in the debate, I explore how the "hormones question"
      becomes entangled in a series of misreadings and displacements through which the
      child's request could potentially be missed. In examining psychoanalytic
      conceptualizations of the trans child's agency, autonomy, and future and the
      relation between the natal body and gender, I ask, how is psychoanalytic
      discourse implicated in the very dilemmas it attempts to elucidate? Specifically,
      the essay examines critically the psychoanalytic use of continuity, authenticity,
      and alignment as implicit ideals, interrogates the focus on mourning as
      therapeutic horizon, and proposes that we conceive of gender as a good-enough
      placeholder with the potential to carry us from the ideal of continuity to an
      ethos of contiguity.

PMID- 29364082
TI  - Eros and Thanatos: A Nondualistic Interpretation: The Dynamic of Drives in
      Personal and Civilizational Development From Freud to Marcuse.
AB  - The Freudian theory of drives gave prominence to the idea that there is an
      inherent principle of entropy, a tendency for dissolution of life, referred to as
      the Death drive, or Thanatos. Freud recognized a counterbalancing tendency for
      sustaining life, known as the Life drive, or Eros. The psychoanalytical
      expounding of the struggle of Eros and Thanatos in the context of the
      civilizational process sparked the philosophical critique of civilization.
      Although Freud tended to consider repression an indispensable dimension of this
      process, the author proposes in this paper that Herbert Marcuse's political
      critique took Freud's metapsychology further philosophically, suggesting a
      nondualistic interpretation of Freud's position.

PMID- 29364083
TI  - Effectiveness of hand cooling and a cooling jacket on post-exercise cooling rates
      in hyperthermic athletes.
AB  - This study compared the effects of a hand cooling glove (~16 degrees C water
      temperature; subatmospheric pressure of -40 mmHg) and a cooling jacket (CJ) on
      post-exercise cooling rates (gastrointestinal core temperature, Tc; skin
      temperature, Tsk) and cognitive performance (the Stroop Colour-Word test). Twelve
      male athletes performed four trials (within subjects, counterbalanced design)
      involving cycling at a workload equivalent to 75% ?O2max in heat (35.7 +/- 0.2
      degrees C, 49.2 +/- 2.6% RH) until a Tc of 39 degrees C or exhaustion occurred. A
      30-min cooling period (in 22.3 +/- 0.3 degrees C, 42.1 +/- 3.6% RH) followed,
      where participants adopted either one-hand cooling (1H), two-hand cooling (2H),
      wore a CJ or no cooling (NC). No significant differences were seen in Tc and Tsk
      cooling rates between trials; however, moderate effect sizes (d = 0.50-0.76)
      suggested Tc cooling rates to be faster for 1H, 2H and CJ compared to NC after 5
      min; 1H and CJ compared to NC after 10 min and for CJ to be faster than 2H at 25
      30 min. Reaction times on the cognitive test were similar between all trials
      after the 30 min cooling/no-cooling period (p > .05). In conclusion, Tc cooling
      rates were faster with 1H and CJ during the first 10 min compared to NC, with
      minimal benefit associated with 2H cooling. Reaction time responses were not
      impacted by the use of the glove(s) or CJ.

PMID- 29364084
TI  - Measured and perceived indices of fluid balance in professional athletes. The use
      and impact of hydration assessment strategies.
AB  - BACKGROUND: To determine athletes perceived and measured indices of fluid balance
      during training and the influence of hydration strategy use on these parameters.
      METHODS: Thirty-three professional rugby union players completed a 120 minute
      training session in hot conditions (35 degrees C, 40% relative humidity). Pre
      training hydration status, sweat loss, fluid intake and changes in body mass (BM)
      were obtained. The use of hydration assessment techniques and players perceptions
      of fluid intake and sweat loss were obtained via a questionnaire. RESULTS: The
      majority of players (78%) used urine colour to determine pre-training hydration
      status but the use of hydration assessment techniques did not influence pre
      training hydration status (1.025 +/- 0.005 vs. 1.023 +/- 0.013 g.ml-1, P = .811).
      Players underestimated sweat loss (73 +/- 17%) to a greater extent than fluid
      intake (37 +/- 28%) which resulted in players perceiving they were in positive
      fluid balance (0.5 +/- 0.8% BM) rather than the measured negative fluid balance (
      1.0 +/- 0.7% BM). Forty-eight percent of players used hydration monitoring
      strategies during exercise but no player used changes in BM to help guide fluid
      replacement. CONCLUSION: Players have difficulty perceiving fluid intake and
      sweat loss during training. However, the use of hydration monitoring techniques
      did not affect fluid balance before or during training.

PMID- 29364085
TI  - Characterization of Diffuse Intrinsic Pontine Glioma Radiosensitivity using
      Synchrotron Microbeam Radiotherapy and Conventional Radiation Therapy In Vitro.
AB  - Synchrotron microbeam radiation therapy is a promising preclinical radiotherapy
      modality that has been proposed as an alternative to conventional radiation
      therapy for diseases such as diffuse intrinsic pontine glioma (DIPG), a
      devastating pediatric tumor of the brainstem. The primary goal of this study was
      to characterize and compare the radiosensitivity of two DIPG cell lines (SF7761
      and JHH-DIPG-1) to microbeam and conventional radiation. We hypothesized that
      these DIPG cell lines would exhibit differential responses to each radiation
      modality. Single cell suspensions were exposed to microbeam (112, 250, 560, 1,180
      Gy peak dose) or conventional (2, 4, 6 and 8 Gy) radiation to produce clonogenic
      cell-survival curves. Apoptosis induction and the cell cycle were also analyzed
      five days postirradiation using flow cytometry. JHH-DIPG-1 cells displayed
      greater radioresistance than SF7761 to both microbeam and conventional radiation,
      with higher colony formation and increased accumulation of G2/M-phase cells.
      Apoptosis was significantly increased in SF7761 cells compared to JHH-DIPG-1
      after microbeam irradiation, demonstrating cell-line specific differential
      radiosensitivity to microbeam radiation. Additionally, biologically equivalent
      doses to microbeam and conventional radiation were calculated based on clonogenic
      survival, furthering our understanding of the response of cancer cells to these
      two radiotherapy modalities.

PMID- 29364086
TI  - The inositol-1,2-cyclic phosphate moiety of the cross-reacting determinant,
      carbohydrate chains, and proteinaceous components are all responsible for the
      cross-reactivity of trypanosome variant surface glycoproteins.
AB  - Salivarian trypanosomes evade the host immune system by continually swapping
      their protective variant surface glycoprotein (VSG) coat. Given that VSGs from
      various trypanosome stocks exhibited cross-reactivity (Camargo et al., Vet.
      Parasitol. 207, 17-33, 2015), we analyzed here which components are the antigenic
      determinants for this cross-reaction. Soluble forms of VSGs were purified from
      four Venezuelan animal trypanosome isolates: TeAp-N/D1, TeAp-ElFrio01, TeAp
      Mantecal01, and TeGu-Terecay323. By using the VSG soluble form from TeAp-N/D1, we
      found that neither the inositol-1,2-cyclic phosphate moiety of the cross-reacting
      determinant nor the carbohydrate chains were exclusively responsible for its
      cross-reactivity. Then, all four purified glycoproteins were digested with papain
      and the resulting peptides were separated by high-performance liquid
      chromatography. Dot blot evaluation of the fractions using sera from trypanosome
      infected animals yielded peptides that possessed cross-reaction activity,
      demonstrating for the first time that proteinaceous epitopes are also responsible
      for the cross-reactivity of trypanosome VSGs.

PMID- 29364087
TI  - A saga about the origin of a journal named CRANIO: The first 3 years.

PMID- 29364088
TI  - Human craniofacial evolution: A cause for obstructive sleep apnea.

PMID- 29364089
TI  - Performance of middle-aged and elderly European minority and majority populations
      on a Cross-Cultural Neuropsychological Test Battery (CNTB).
AB  - OBJECTIVE: The aim of this study was to examine test performance on a cross
      cultural neuropsychological test battery for assessment of middle-aged and
      elderly ethnic minority and majority populations in western Europe, and to
      present preliminary normative data. METHOD: The study was a cross-sectional multi
      center study. Tests in the European Cross-Cultural Neuropsychological Test
      Battery (CNTB) cover several cognitive domains, including global cognitive
      function, memory, executive functions, and visuospatial functions. RESULTS: A
      total of 330 participants were included: 14 Moroccan, 45 Pakistani/Indian
      Punjabi, 41 Polish, 66 Turkish, and 19 former Yugoslavian minority participants,
      and 145 western European majority participants. Significant differences between
      ethnic groups were found on most CNTB measures. However, ethnic groups differed
      greatly in demographic characteristics and differences in test scores were mainly
      related to educational differences, explaining an average of 15% of the variance.
      Preliminary multicultural CNTB normative data dichotomized by education and age
      were constructed using overlapping cells. Applying this normative data across the
      whole sample resulted in an acceptable number of participants scoring in the
      impaired range across all ethnic groups. Factor analyses found the CNTB to have a
      stable and clinically meaningful factor structure. CONCLUSIONS: The CNTB
      represents the first European joint effort to establish neuropsychological
      measures appropriate for ethnic minority populations in western Europe. The CNTB
      can be applied in approximately 60 min, covers several cognitive domains, and
      appears appropriate for assessment of the targeted populations. However, due to
      the small sample size in some ethnic groups further studies are needed replicate
      and support this.

PMID- 29364090
TI  - Serum concentrations of Cyclophilin A in patients with Nonalcoholic Fatty Liver
      Disease.
AB  - AIM: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of
      chronic liver disease and its incidence is rising worldwide. Cyclophilin A (CyPA)
      is a protein, which is secreted under the presence of oxidative stress and
      hyperglycemia, and it plays role in proinflammatory signal reduction. In this
      study we investigated serum levels of CyPA in patients with biopsy proven NAFLD
      and examined their association with clinical and histological phenotypes.
      METHODS: In this study, we identified serum levels of CyPA in patients with NAFLD
      (n=52) and healthy controls without evidence of any liver disease (n=44). The
      levels of CyPA were measured by enzyme-linked immunosorbent assay and were
      compared between two study groups. Furthermore, serum levels of CyPA were
      assessed in relation to the clinical characteristics of the study participants.
      RESULTS: Serum levels of CyPA were significantly higher in patients with NAFLD
      (3,8+/-2,6 ug/ml, P=0.03) compared to healthy controls (2,8+/-1,8 ug/ml).
      Moreover, concentrations of CyPA were 2,8+/-1,8, 3,4+/-2,3, and 4,2+/-2,9 ug/ml
      in control group, non-diabetic and diabetic NAFLD patients, respectively. The
      difference between the groups was statistically significant (P=0.04). There was
      significant correlation between the serum concentrations of CyPA and glucose
      levels (P=0.01), but there was no significant correlation with other clinical and
      histologic parameters. CONCLUSIONS: Our data suggest that CyPA levels are
      elevated in patients with NAFLD, especially in patients with diabetes. (Acta
      gastroenterol. belg., 2017, 80, 3-7).

PMID- 29364091
TI  - Observation of combined/optimized therapy of Lamivudine and Adefovir Dipivoxyl
      for hepatitis B-induced decompensated cirrhosis with baseline HBV DNA>1,000
      IU/mL.
AB  - OBJECTIVE: This study aimed to observe and compare the efficacy and safety of the
      combined therapy and two different optimized therapies of lamivudine (LAM) and
      adefovir dipivoxil (ADV), as well as entecavir (ETV) monotherapy in patients with
      hepatitis B-induced decompensated cirrhosis. Method : A total of 127 patients
      with decompensated cirrhosis were divided into four groups, and each group
      received different doses of regimens: initial combination of LAM and ADV, ADV add
      on therapies with previous 12-week LAM, ADV add-on therapies with previous 24
      week LAM, and ETV monotherapy. RESULTS: At the end of the treatment, the level of
      alanine amino-transferase (ALT), albumin (ALB) and total bilirubin (TBIL) in the
      combination therapy group and 12-week optimized therapy group were significantly
      improved. For the 24-week optimized therapy group, only ALT levels revealed a
      significant improvement. There were no obvious differences in the normalization
      rate of ALT, negative conversion rate of HBV DNA and HBeAg, as well as
      improvement in Child-Pugh scores among the combination therapy group, 12-week
      optimized therapy group, and ETV monotherapy group. However, the difference among
      these three groups and the 24-week optimized therapy group were significant.
      Differences were not observed in the HBeAg seroconversion between each group.
      Differences in blood urea nitrogen, serum creatinine, creatine kinase, or other
      serious adverse effects were not observed in each group at the end of the 96-week
      treatment. CONCLUSION: Combination therapy and early ADV addition were the
      preferred approaches in the antiviral strategy for the treatment of hepatitis B
      induced decompensated cirrhosis.

PMID- 29364092
TI  - Nodular Regenerative Hyperplasia in HIV-positive patients : a case series and
      review of the literature.
AB  - Nodular regenerative hyperplasia (NRH) is a well-described condition that leads
      to non-cirrhotic portal hypertension and is histologically characterised by a
      nodular transformation of the liver without fibrosis. It seems to be a
      consequence of obliterative portal venopathy of small hepatic veins. Its precise
      aetiology remains to be clearly determined. NRH was reported to occur in HIV
      positive patients ten years ago. In this article, three consecutive clinical
      cases of HIV-related NRH were identified in a high volume reference centre of HIV
      positive patients and are presented. Clinical, diagnostic aspects and strategies
      for management of this under-diagnosed medical condition in the HIV population
      are also developed.

PMID- 29364093
TI  - The role of insulin - like growth factor - 1 on steatohepatitis.
AB  - PURPOSE: Recent studies have revealed that growth hormone and STAT5 were related
      to hepatosteatosis in mice. Loss of signal transducer and activator of
      transcription factor-5 leads to hepatosteatosis and impaired liver regeneration.
      We aimed to investigate the role of IGF-1 in steatosis with normal (SNLFT) and
      disturbed liver function tests (SDLFT) in humans. METHODS: We included 272 NAFLD
      patients and 110 age, sex and body mass index (BMI)-matched healty controls. We
      measured routine blood biochemistry and complete blood count, IGF-1, insulin, c
      peptide, ferritin, hsCRP, ESR and HOMA-IR. We subdivided NAFLD patients into
      SNLFT and SDLFT subgroups. RESULTS: ge, sex and BMI were similar between NAFLD
      and controls. IGF-1 levels were significantly lower in NAFLD patients (120,6+/
      48,2) than controls (148,9+/-53,8), (<0,0001). IGF-1 levels were also lower in
      SDLFT subgroup (93,4+/-27,8) than SNLFT subgroup (123,1+/-49,0), (p:0,032). Waist
      circumference, fasting blood glucose, HbA1c, uric acid, hsCRP, AST, ALT, GGT,
      WBC, hemoglobin, hematocrit, ferritin, insulin, c-peptid and HOMA-IR measurements
      were significantly higher in NAFLD patients than controls (for all values:
      p<0,0001).Cholesterol (p:0,026), triglycerides (p<0,0001), ESR (p:0,006) were
      significantly higher in NAFLD patients than controls. HDL-chelesterol levels were
      significantly lower (p:0,002) in NAFLD patients than controls. CONCLUSION: This
      study supported previous findings of experi-mental studies in that, IGF-1 levels
      were lower in SNLFT and SDLFT. Growth hormone-IGF-1 system may be involved in the
      pathogenesis of NAFLD.

PMID- 29364094
TI  - Very low rates of Helicobacter pylori infection in organ transplant recipients
      presenting with peptic ulcer disease.
AB  - BACKGROUND: Leading causative factors of peptic ulcer disease (PUD) in the
      general population are infection with Helicobacter pylori (HP) and exposure to
      non-steroidal anti-inflammatory drugs (NSAID). We hypothesized that this may be
      different in transplant recipients given increased exposure of immunosuppressive
      and anti-microbial drugs. METHODS: We performed a retrospective single center
      analysis of all patients presenting with PUD to the endoscopy unit at a tertiary
      care and transplant center in Germany between 2006 and 2013. PUD was diagnosed by
      upper endoscopy. HP was identified by biopsy and histology. Organ transplant
      recipients were compared to non-transplant recipients (control group). RESULTS:
      66 patients with PUD were identified in the study period. 12% (44/366) had
      previously received an organ transplant. 7% (3/44) of transplant recipients were
      found to be positive for HP compared to 25% (81/322) in the control group
      (p=0.007). Even when excluding patients taking proton-pump-inhibitors (PPI) from
      the analysis rates were similar with 30% (65/214) of the ulcers being HP positive
      in the control group compared to 14% (1/7) in transplant recipients (p=0.006).
      Furthermore, in the transplant recipient group rates of being in intensive care,
      concurrent PPI and concurrent antibiotic medication were significantly higher
      than in the control group. CONCLUSION: Organ transplant recipients with PUD have
      lower rates of Helicobacter pylori positivity compared to the general population.

PMID- 29364095
TI  - Immunohistochemical expression of CDX2, CK7, HER2 and HER4 in periampullary
      adenocarcinoma : implications for clinicopathology and patient outcomes.
AB  - Background: Periampullary carcinomas originate from the pancreatic head, the
      ampulla, the distal bile duct, or the duodenum. The expression of CK7 and CDX2
      has been used in the classification of periampullary carcinomas. There is
      prognostic value of human epidermal growth factor receptor (HER) 2 and HER 4,
      which have been linked to poor prognosis in several types of tumors, such as
      breast and gastric carcinomas. We aimed to evaluate the expression and prognostic
      value of CDX2, CK7, HER 2, and HER4 in periampullary adenocarcinoma. Patients and
      Methods: We retrospectively selected 98 patients who had undergone
      pancreatoduodenectomy for periampullary adenocarcinoma at our pathology
      department. The tumor location, pathological subtype, involvement of vessels and
      lymph nodes, perineural invasion, clinical follow-up, and tumorstage were noted.
      Immunohistochemistry was performed for CK7, CDX2, HER2, and HER4. Results: CDX2
      staining was predictive of perineural invasion. Additionally, there was a
      significant association between the overexpression of HER2 and HER4 and the
      presence of perineural invasion. HER4 was significantly positive in patients with
      the pancreatobiliary subtype compared with patients with the intestinal subtype.
      Patients with the pancreatobiliary subtype, lymph node involvement, and advanced
      pT and UICC stages had significantly lower median survival. Conclusion: Our
      findings suggest that only pancreatobiliary subtype, lymph node involvement and
      advanced pT and UICC stages were independent predictors of short survival, but
      the ampulla tumor location predicted a significantly better survival time. The
      immunohistochemical expression of CDX2, CK7, HER4, and HER2, vessel involvement,
      and perineural invasion were not associated with the survival of patients with
      periampullary adenocarcinoma.

PMID- 29364096
TI  - The efficiency of Levofloxacin Containing Sequential Therapy with or without
      Bismuth, in Helicobacter Pylori Eradication, in Non-ulcer Dyspepsia.
AB  - INTRODUCTION: The aim of this study is to determine the efficiency of
      levofloxacin containing sequential therapy with or without bismuth in
      Helicobacter pylori (Hp) eradication in nonulcer dyspepsia. MATERIALS AND
      METHODS: One hundred and ninety Hp-positive patients with the pre-diagnosis of
      nonulcer dyspepsia were included in this study. Patients were randomized into 2
      groups and 95 individuals were included in each group. The first group was
      administered levofloxacin containing sequential therapy with bismuth, whereas the
      second group was administered only levofloxacin containing sequential therapy.
      Rates of therapy discontinuation and eradication success were compared between
      the 2 groups. Furthermore, symptomatic healing rates were com-pared between
      patients in whom Hp eradication was achieved and in whom it was not achieved.
      RESULTS: Ninety-one patients from each group applied for follow-up after
      treatment. It was found that 7/91(7.6%) patients from the first group and
      5/91(5.4%) patients from the second group did not complete the therapy (p >0.05).
      In patients who completed therapy, Hp eradication was achieved in 72 out of the
      84 patients (85.2%) from the first group and 71 out of 86 patients (82.6%) from
      the second group (p > 0.05). In addition, symptomatic healing occurred in 125 out
      of 143 patients (87.4%) in whom Hp was eradicated and 12 out of 27 (44.4%)
      patients in whom Hp was not eradicated (p < 0.001). CONCLUSION: Levofloxacin
      containing sequential therapy for 14 days is quite effective and well-tolerated
      choice for Hp eradication. However, adding bismuth to sequential therapy does not
      significantly improve Hp eradication success rates. Therefore, Hp eradication is
      beneficial and necessary in patients with nonulcer dyspepsia.

PMID- 29364097
TI  - Contribution of PNPLA3 gene to the natural history of liver diseases.
AB  - n 2008, a genome-wide association studies (GWAS) showed a strong association
      between a variant (rs738409 C>G p.I148M) in the PNPLA3 and nonalcoholic fatty
      liver disease. Further replication studies have shown robust associations between
      PNPLA3 and steatosis, fibrosis/cirrhosis, and hepatocellular carcinoma on a
      background of metabolic, alcoholic, and viral insults. The PNPLA3 protein has
      lipase activity towards triglycerides in hepatocytes and retinyl esters in
      hepatic stellate cells. The I148M substitution leads to a loss of function
      promoting triglyceride accumulation in hepatocytes. Although PNPLA3 function has
      been extensively studied, the molecular mechanisms leading to hepatic fibrosis
      and carcinogenesis remain unclear. This unsuspected association has highlighted
      the fact that liver fat metabolism may have a major impact on the pathophysiology
      of liver disease. Conversely, alone, this locus may have limited predictive value
      with regard to liver disease outcomes in clinical practice. Additional studies at
      the genome-wide level will be required to identify new variants associated with
      liver damage and cancer to explain a greater proportion of the heritability of
      these phenotypes. Thus, incorporating PNPLA3 and other genetic variants in
      combination with clinical data will allow for the development of tailored
      predictive models. This attractive approach should be evaluated in prospective
      cohorts. (Acta gastroenterol. belg., 2017, 80, 43-51).

PMID- 29364098
TI  - Liver disease late in pregnancy without pre-eclampsia.
AB  - We describe the case of a first twin pregnancy in a 27 year old patient, who
      experienced acute onset epigastric and right upper quadrant pain at a gestational
      age of 32 weeks and 2 days. She was diagnosed with acute liver and renal failure
      and possible disseminated intravascular coagulopathy (DIC) syndrome without pre
      eclampsia. Early labor induction was mandatory to save both mother and foetuses.
      In this overview we describe the differential diagnosis of severe pregnancy
      related liver injury in the third trimester of pregnancy without pre-eclampsia.
      (Acta gastroenterol. belg., 2017, 80, 53-57).

PMID- 29364099
TI  - A rare cause of acute pancreatitis: Hantavirus infection.
AB  - Hantaviruses cause potentially fatal two different systemic infectious diseases
      in humans named as hemorrhagic fever with renal syndrome (HFRS) and Hantavirus
      pulmonary syndrome. The clinical features of HFRS are hemorrhage, fever,
      thrombocytopenia and acute renal insufficiency frequently observed. HFRS shows
      distinctive clinical manifestations throughout from acute influenza-like febrile
      illness to shock. Although a large portion of HRFS patients present with a
      complaint of abdominal pain, acute pancreatitis is a rare complication of HFRS.
      No specific treatment protocol has been described for HRFS and supportive
      treatment is the basic approach. The rate of success enhanced with early
      diagnosis and intensive care support. Clinicians should be alert to the HFRS in
      patients with acute pancreatitis associated with systemic viral infection. We
      describe a case with HFRS who has presented with acute kidney injury,
      thrombocytopenia and acute pancreatitis. The patient was treated by supportive
      management successfully.

PMID- 29364100
TI  - Unsuccessful transjugular intrahepatic portosystemic shunt for a patient with
      right heart failure and portal hypertension.
AB  - A 60-year-old women with a history of congenital pulmonary valve stenosis
      developed right heart failure, cardiac cirrhosis and end-stage renal disease
      requiring renal replacement therapy. Cirrhosis was complicated by portal
      hypertension, resulting in intractable gastro-intestinal bleedings despite
      optimal treatment with beta-blockers and endoscopic band ligation. Because of
      fears for worsening right heart failure, a decision for placement of a
      transjugular intrahepatic portosystemic shunt (TIPS) was initially turned down.
      However, as intractable bleeding problems persisted and caused heavy transfusion
      needs, TIPS was ultimately performed as a rescue procedure. Although TIPS
      successfully reduced the hepatic venous pressure gradient from 16 mmHg to 4 mmHg,
      portal pressure remained high at 14 mmHg because of persisting right heart
      failure with elevated central venous pressure. Hepatic encephalopathy soon
      developed after TIPS placement and culminated in multi-organ failure after
      another episode of gastro-intestinal bleeding. At this point, the family of the
      patient decided to withdraw care and the patient died subsequently. This case
      illustrates how important it is to diagnose and optimally treat right heart
      failure before cardiac cirrhosis with its impending complications emerges.
      Although TIPS may effectively treat complications of portal hypertension in the
      context of cirrhosis, persisting right heart failure may abrogate its beneficial
      effects.

PMID- 29364101
TI  - Rectal red blood loss in a healthy toddler is not always a juvenile polyp.
AB  - Aim Heterotopic gastric mucosa is a well-known congenital anomaly in Meckel's
      diverticula and duplication cysts. Solitary heterotopic gastric mucosa in the
      rectum is a rare and frequently overlooked abnormality. Starting from a patient
      history, the literature is searched and all cases reported over the past 20 years
      are reviewed and compared to a summary of the older cases. Differences between
      adult and childhood presentation are outlined and our patient is compared with
      prior reported cases. Case A 3-year-old girl presented with recurrent rectal
      blood loss caused by heterotopic gastric mucosa without duplication cyst. She was
      endoscopically treated with two-stage endoscopic surgical dissection (ESD). Up to
      now, rectal heterotopic gastric mucosa has been reported in 34 adults and 24
      children, including this patient. There is an overall male dominance (69%).
      Presenting complaints in children were recurrent fresh blood loss per anum (96%),
      pain (46%), perineal ulcers (25%), diarrhoea (8%) and one patient had an ano
      cutaneous fistula. Endoscopy revealed a mucosal elevation with a slightly
      different aspect (33%), a polyp (42%) and a solitary ulcer (25%). Endoscopy in
      adults reveals more frequently polyps compared to children. Treatment in
      childhood is mainly surgical where adults are more frequently treated with
      endoscopic techniques. Conclusion In a child with recurrent rectal bleeding in
      good general health, it is important to withhold heterotopic gastric mucosa in
      the differential diagnosis and take sufficient biopsies during endoscopy.

PMID- 29364102
TI  - Management of hypertriglyceridemia induced acute pancreatitis and therapeutic
      plasmapheresis : Report of nine cases and review of literature.
AB  - Hypertriglyceridemia is one of the rare causes of the acute pancreatitis. The
      prevalance of hypertriglyceridemia has increased recently due to the changing
      eating habits, sedentary lifestyle, alcohol consumption, obesity and concomitant
      diabetes mellitus. Therefore, the frequency of the acute pancreatitis due to
      hypertriglyceridemia may increase in coming years. Diagnosis of the acute
      pancreatitis by hypertriglyceridemia can be overlooked easily and may be very
      severe if untreated accurately on time. In addition to the standard management of
      pancreatitis, specific treatment for hypertriglyceridemia that is insulin,
      heparin and anti-hypertriglyceridemic drugs are used. Therapeutic plasmapheresis
      is the last treatment option and seems the most effective one in this subject
      through developing device and membrane technologies when we review the current
      literature. Not only triglycerides but also proinflammatory cytokines and
      adhesion molecules that play an active role in pathogenesis are removed by
      plasmapheresis. So, the effectiveness of treatment appears promising. However,
      the exact pathophysiology of hypertriglyceridemia-induced pancreatitis could not
      be fully understood and the majority of published experience comes from the case
      reports and the benefit of randomized clinical trials is not available.
      Therefore, there are no data about what are the exact indications and when we
      start therapeutic plasmapheresis in literature. This manuscript describes our
      hospital experience with treatment options and analyzes reports published
      recently about plasmapheresis as a treatment modality for hypertriglyceridemia
      induced acute pancreatitis.

PMID- 29364103
TI  - An unusual cause of dyspepsia due to a retained epicardial pacing wire.

PMID- 29364104
TI  - Adenocarcinoma of the Rectum in a 27-year-old Patient with Usher Syndrome : Is
      there a Genetic Correlation?

PMID- 29364105
TI  - Spontaneous isolated mesenteric fibromatosis associated with small bowel
      obstruction.

PMID- 29364106
TI  - Trichobezoar and Rapunzel syndrome : an unusual cause of abdominal mass.

PMID- 29364107
TI  - All caecal ulcers is not Crohn's: Think Travel-Think again.

PMID- 29364108
TI  - Gastric Ulcers Related to The Transarterial Radioembolization of Yittrium-90 in A
      Patient with Paraganglioma.

PMID- 29364110
TI  - Fistulization between stomach and transverse colon because of nasogastric feeding
      tube.

PMID- 29364109
TI  - Azathioprine-induced acute pancreatitis in inflammatory bowel disease : natural
      history and severity spectrum.

PMID- 29364111
TI  - Diffuse nodular duodenitis in a woman presenting with dyspepsia and weight loss.
AB  - Duodenal nodularity is an uncommon endoscopic finding charac-trized by numerous
      visible mucosal nodules in the duodenum. It is important to consider giardiasis
      in patients with symptoms include abdominal pain, nausea, anorexia, diarrhea,
      vomiting, weight loss and abdominal distension. It is also important to remind
      giardiasis in patients with duodenal nodularity.

PMID- 29364112
TI  - A giant polypoid mass leading to obstruction in the colon.

PMID- 29364114
TI  - Age is just a number.
AB  - The naked mole rat defies the Gompertz law and shows no sign of increased
      mortality risk as it gets older.

PMID- 29364113
TI  - aPKC-mediated displacement and actomyosin-mediated retention polarize Miranda in
      Drosophila neuroblasts.
AB  - Cell fate assignment in the nervous system of vertebrates and invertebrates often
      hinges on the unequal distribution of molecules during progenitor cell division.
      We address asymmetric fate determinant localization in the developing Drosophila
      nervous system, specifically the control of the polarized distribution of the
      cell fate adapter protein Miranda. We reveal a step-wise polarization of Miranda
      in larval neuroblasts and find that Miranda's dynamics and cortical association
      are differently regulated between interphase and mitosis. In interphase, Miranda
      binds to the plasma membrane. Then, before nuclear envelope breakdown, Miranda is
      phosphorylated by aPKC and displaced into the cytoplasm. This clearance is
      necessary for the subsequent establishment of asymmetric Miranda localization.
      After nuclear envelope breakdown, actomyosin activity is required to maintain
      Miranda asymmetry. Therefore, phosphorylation by aPKC and differential binding to
      the actomyosin network are required at distinct phases of the cell cycle to
      polarize fate determinant localization in neuroblasts.

PMID- 29364117
TI  - Improved Visualization of Gastrointestinal Slow Wave Propagation Using a Novel
      Wavefront-Orientation Interpolation Technique.
AB  - OBJECTIVE: High-resolution mapping of gastrointestinal (GI) slow waves is a
      valuable technique for research and clinical applications. Interpretation of high
      resolution GI mapping data relies on animations of slow wave propagation, but
      current methods remain as rudimentary, pixelated electrode activation animations.
      This study aimed to develop improved methods of visualizing high-resolution slow
      wave recordings that increases ease of interpretation. METHODS: The novel method
      of "wavefront-orientation" interpolation was created to account for the planar
      movement of the slow wave wavefront, negate any need for distance calculations,
      remain robust in atypical wavefronts (i.e., dysrhythmias), and produce an
      appropriate interpolation boundary. The wavefront-orientation method determines
      the orthogonal wavefront direction and calculates interpolated values as the mean
      slow wave activation-time (AT) of the pair of linearly adjacent electrodes along
      that direction. Stairstep upsampling increased smoothness and clarity. RESULTS:
      Animation accuracy of 17 human high-resolution slow wave recordings (64-256
      electrodes) was verified by visual comparison to the prior method showing a clear
      improvement in wave smoothness that enabled more accurate interpretation of
      propagation, as confirmed by an assessment of clinical applicability performed by
      eight GI clinicians. Quantitatively, the new method produced accurate
      interpolation values compared to experimental data (mean difference 0.02 +/- 0.05
      s) and was accurate when applied solely to dysrhythmic data (0.02 +/- 0.06 s),
      both within the error in manual AT marking (mean 0.2 s). Mean interpolation
      processing time was 6.0 s per wave. CONCLUSION AND SIGNIFICANCE: These novel
      methods provide a validated visualization platform that will improve analysis of
      high-resolution GI mapping in research and clinical translation.

PMID- 29364115
TI  - Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish
      valvulogenesis.
AB  - Endothelial cells respond to different levels of fluid shear stress through
      adaptations of their mechanosensitivity. Currently, we lack a good understanding
      of how this contributes to sculpting of the cardiovascular system. Cerebral
      cavernous malformation (CCM) is an inherited vascular disease that occurs when a
      second somatic mutation causes a loss of CCM1/KRIT1, CCM2, or CCM3 proteins.
      Here, we demonstrate that zebrafish Krit1 regulates the formation of cardiac
      valves. Expression of heg1, which encodes a binding partner of Krit1, is
      positively regulated by blood-flow. In turn, Heg1 stabilizes levels of Krit1
      protein, and both Heg1 and Krit1 dampen expression levels of klf2a, a major
      mechanosensitive gene. Conversely, loss of Krit1 results in increased expression
      of klf2a and notch1b throughout the endocardium and prevents cardiac valve
      leaflet formation. Hence, the correct balance of blood-flow-dependent induction
      and Krit1 protein-mediated repression of klf2a and notch1b ultimately shapes
      cardiac valve leaflet morphology.

PMID- 29364116
TI  - Naked Mole-Rat mortality rates defy gompertzian laws by not increasing with age.
AB  - The longest-lived rodent, the naked mole-rat (Heterocephalus glaber), has a
      reported maximum lifespan of >30 years and exhibits delayed and/or attenuated age
      associated physiological declines. We questioned whether these mouse-sized,
      eusocial rodents conform to Gompertzian mortality laws by experiencing an
      exponentially increasing risk of death as they get older. We compiled and
      analyzed a large compendium of historical naked mole-rat lifespan data with >3000
      data points. Kaplan-Meier analyses revealed a substantial portion of the
      population to have survived at 30 years of age. Moreover, unlike all other
      mammals studied to date, and regardless of sex or breeding-status, the age
      specific hazard of mortality did not increase with age, even at ages 25-fold past
      their time to reproductive maturity. This absence of hazard increase with age, in
      defiance of Gompertz's law, uniquely identifies the naked mole-rat as a non-aging
      mammal, confirming its status as an exceptional model for biogerontology.

PMID- 29364119
TI  - Consistency of Long-Term Subdural Electrocorticography in Humans.
AB  - OBJECTIVE: Subdural electrocorticography (ECoG) can provide a robust control
      signal for a brain-computer interface (BCI). However, the long-term recording
      properties of ECoG are poorly understood as most ECoG studies in the BCI field
      have only used signals recorded for less than 28 days. We assessed human ECoG
      recordings over durations of many months to investigate changes to recording
      quality that occur with long-term implantation. METHODS: We examined changes in
      signal properties over time from 15 ambulatory humans who had continuous subdural
      ECoG monitoring for 184-766 days. RESULTS: Individual electrodes demonstrated
      varying changes in frequency power characteristics over time within individual
      patients and between patients. Group level analyses demonstrated that there were
      only small changes in effective signal bandwidth and spectral band power across
      months. High-gamma signals could be recorded throughout the study, though there
      was a decline in signal power for some electrodes. CONCLUSION: ECoG-based BCI
      systems can robustly record high-frequency activity over multiple years, albeit
      with marked intersubject variability. SIGNIFICANCE: Group level results
      demonstrated that ECoG is a promising modality for long-term BCI and neural
      prosthesis applications.

PMID- 29364118
TI  - Robust Multicontrast MRI Spleen Segmentation for Splenomegaly Using Multi-Atlas
      Segmentation.
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) is an essential imaging modality in
      noninvasive splenomegaly diagnosis. However, it is challenging to achieve spleen
      volume measurement from three-dimensional MRI given the diverse structural
      variations of human abdomens as well as the wide variety of clinical MRI
      acquisition schemes. Multi-atlas segmentation (MAS) approaches have been widely
      used and validated to handle heterogeneous anatomical scenarios. In this paper,
      we propose to use MAS for clinical MRI spleen segmentation for splenomegaly.
      METHODS: First, an automated segmentation method using the selective and
      iterative method for performance level estimation (SIMPLE) atlas selection is
      used to address the concerns of inhomogeneity for clinical splenomegaly MRI.
      Then, to further control outliers, semiautomated craniocaudal spleen length-based
      SIMPLE atlas selection (L-SIMPLE) is proposed to integrate a spatial prior in a
      Bayesian fashion and guide iterative atlas selection. Last, a graph cuts
      refinement is employed to achieve the final segmentation from the probability
      maps from MAS. RESULTS: A clinical cohort of 55 MRI volumes (28 T1 weighted and
      27 T2 weighted) was used to evaluate both automated and semiautomated methods.
      CONCLUSION: The results demonstrated that both methods achieved median Dice , and
      outliers were alleviated by the L-SIMPLE (?1 min manual efforts per scan), which
      achieved 0.97 Pearson correlation of volume measurements with the manual
      segmentation. SIGNIFICANCE: In this paper, spleen segmentation on MRI
      splenomegaly using MAS has been performed.

PMID- 29364121
TI  - From Cell to Tissue Properties-Modeling Skin Electroporation With Pore and Local
      Transport Region Formation.
AB  - Current models of tissue electroporation either describe tissue with its bulk
      properties or include cell level properties, but model only a few cells of simple
      shapes in low-volume fractions or are in two dimensions. We constructed a three
      dimensional model of realistically shaped cells in realistic volume fractions. By
      using a 'unit cell' model, the equivalent dielectric properties of whole tissue
      could be calculated. We calculated the dielectric properties of electroporated
      skin. We modeled electroporation of single cells by pore formation on
      keratinocytes and on the papillary dermis which gave dielectric properties of the
      electroporated epidermis and papillary dermis. During skin electroporation, local
      transport regions are formed in the stratum corneum. We modeled local transport
      regions and increase in their radii or density which affected the dielectric
      properties of the stratum corneum. The final model of skin electroporation
      accurately describes measured electric current and voltage drop on the skin
      during electroporation with long low-voltage pulses. The model also accurately
      describes voltage drop on the skin during electroporation with short high-voltage
      pulses. However, our results indicate that during application of short high
      voltage pulses additional processes may occur which increase the electric
      current. Our model connects the processes occurring at the level of cell
      membranes (pore formation), at the level of a skin layer (formation of local
      transport region in the stratum corneum) with the tissue (skin layers) and even
      level of organs (skin). Using a similar approach, electroporation of any tissue
      can be modeled, if the morphology of the tissue is known.

PMID- 29364120
TI  - Adaptive Sparse Multiple Canonical Correlation Analysis With Application to
      Imaging (Epi)Genomics Study of Schizophrenia.
AB  - Finding correlations across multiple data sets in imaging and (epi)genomics is a
      common challenge. Sparse multiple canonical correlation analysis (SMCCA) is a
      multivariate model widely used to extract contributing features from each data
      while maximizing the cross-modality correlation. The model is achieved by using
      the combination of pairwise covariances between any two data sets. However, the
      scales of different pairwise covariances could be quite different and the direct
      combination of pairwise covariances in SMCCA is unfair. The problem of "unfair
      combination of pairwise covariances" restricts the power of SMCCA for feature
      selection. In this paper, we propose a novel formulation of SMCCA, called
      adaptive SMCCA, to overcome the problem by introducing adaptive weights when
      combining pairwise covariances. Both simulation and real-data analysis show the
      outperformance of adaptive SMCCA in terms of feature selection over conventional
      SMCCA and SMCCA with fixed weights. Large-scale numerical experiments show that
      adaptive SMCCA converges as fast as conventional SMCCA. When applying it to
      imaging (epi)genetics study of schizophrenia subjects, we can detect significant
      (epi)genetic variants and brain regions, which are consistent with other existing
      reports. In addition, several significant brain-development related pathways,
      e.g., neural tube development, are detected by our model, demonstrating imaging
      epigenetic association may be overlooked by conventional SMCCA. All these results
      demonstrate that adaptive SMCCA are well suited for detecting three-way or
      multiway correlations and thus can find widespread applications in multiple omics
      and imaging data integration.

PMID- 29364122
TI  - A New Adaptive Gamma Correction Based Algorithm Using DWT-SVD for Non-Contrast CT
      Image Enhancement.
AB  - The performances of medical image processing techniques, in particular CT scans,
      are usually affected by poor contrast quality introduced by some medical imaging
      devices. This suggests the use of contrast enhancement methods as a solution to
      adjust the intensity distribution of the dark image. In this paper, an advanced
      adaptive and simple algorithm for dark medical image enhancement is proposed.
      This approach is principally based on adaptive gamma correction using discrete
      wavelet transform with singular-value decomposition (DWT-SVD). In a first step,
      the technique decomposes the input medical image into four frequency sub-bands by
      using DWT and then estimates the singular-value matrix of the low-low (LL) sub
      band image. In a second step, an enhanced LL component is generated using an
      adequate correction factor and inverse singular value decomposition (SVD). In a
      third step, for an additional improvement of LL component, obtained LL sub-band
      image from SVD enhancement stage is classified into two main classes (low
      contrast and moderate contrast classes) based on their statistical information
      and therefore processed using an adaptive dynamic gamma correction function. In
      fact, an adaptive gamma correction factor is calculated for each image according
      to its class. Finally, the obtained LL sub-band image undergoes inverse DWT
      together with the unprocessed low-high (LH), high-low (HL), and high-high (HH)
      sub-bands for enhanced image generation. Different types of non-contrast CT
      medical images are considered for performance evaluation of the proposed contrast
      enhancement algorithm based on adaptive gamma correction using DWT-SVD (DWT-SVD
      AGC). Results show that our proposed algorithm performs better than other state
      of-the-art techniques.

PMID- 29364123
TI  - CEP4HFP: Complex Event Processing for Heart Failure Prediction.
AB  - This paper presents a novel health analysis approach for heart failure
      prediction. It is based on the use of complex event processing (CEP) technology,
      combined with statistical approaches. A CEP engine processes incoming health data
      by executing threshold-based analysis rules. Instead of having to manually set up
      thresholds, our novel statistical algorithm automatically computes and updates
      thresholds according to recorded historical data. Experimental results
      demonstrate the merits of our approach in terms of speed, precision, and recall.

PMID- 29364124
TI  - The Effect of Solvents and Rare-Earth Element (Er, Yb) Doping on Suspension
      Stability of Sol-Gel Titania Nanoparticles.
AB  - The effects of solvent on the suspension stability of titanium dioxide (TiO2)
      nanoparticle (NP)-doped rare-earth elements (Er and Yb) were evaluated. Pure and
      doped TiO2 NPs were successfully prepared by the sol-gel method under the
      supercritical drying conditions of ethanol. Doped nanopowders were prepared with
      5 mol% Er or 5 mol% Yb concentration, and co-doped nanopowders were prepared with
      fixed 5 mol% Er concentration and various Yb concentrations of 5 and 10 mol%.
      TiO2 NP suspensions with diverse solvents, such as water, ethanol, methanol, and
      butanol, were prepared. The nanopowders were characterized by studying their
      structural and morphology properties. The NP size analysis revealed the average
      size of TiO2 as approximately around 7-12 nm. Suspensions of TiO2 NPs in
      different solvents were prepared by a two-step powder dispersion process using
      several ultrasonication methods. The aim of this paper was to prepare a stable
      suspension for a certain time period and then to produce doped and undoped TiO2
      NP coatings for photovoltaic application. The effects of concentration, dopants,
      and solvents on the dispersibility and stability of TiO2 suspensions were
      evaluated. The UV-visible spectroscopy, zeta potential measurements, particle
      size distribution, SEM, and Hamaker 2 software confirm that the 5%Er-10%:TiO2
      suspension exhibits a good stability and stable suspension improved by co-doped
      rare.

PMID- 29364125
TI  - Touchable Computing: Computing-Inspired Bio-Detection.
AB  - We propose a new computing-inspired bio-detection framework called touchable
      computing (TouchComp). Under the rubric of TouchComp, the best solution is the
      cancer to be detected, the parameter space is the tissue region at high risk of
      malignancy, and the agents are the nanorobots loaded with contrast medium
      molecules for tracking purpose. Subsequently, the cancer detection procedure
      (CDP) can be interpreted from the computational optimization perspective: a
      population of externally steerable agents (i.e., nanorobots) locate the optimal
      solution (i.e., cancer) by moving through the parameter space (i.e., tissue under
      screening), whose landscape (i.e., a prescribed feature of tissue environment)
      may be altered by these agents but the location of the best solution remains
      unchanged. One can then infer the landscape by observing the movement of agents
      by applying the "seeing-is-sensing" principle. The term "touchable" emphasizes
      the framework's similarity to controlling by touching the screen with a finger,
      where the external field for controlling and tracking acts as the finger. Given
      this analogy, we aim to answer the following profound question: can we look to
      the fertile field of computational optimization algorithms for solutions to
      achieve effective cancer detection that are fast, accurate, and robust? Along
      this line of thought, we consider the classical particle swarm optimization (PSO)
      as an example and propose the PSO-inspired CDP, which differs from the standard
      PSO by taking into account realistic in vivo propagation and controlling of
      nanorobots. Finally, we present comprehensive numerical examples to demonstrate
      the effectiveness of the PSO-inspired CDP for different blood flow velocity
      profiles caused by tumor-induced angiogenesis. The proposed TouchComp bio
      detection framework may be regarded as one form of natural computing that employs
      natural materials to compute.

PMID- 29364126
TI  - Influence of Tuning Element Relief Patches on Pain as Analyzed by the Resonant
      Recognition Model.
AB  - Tuning element relief patches (TERPs) are silicon-based titanium salt infused
      adhesive patches that have been developed by Tuning Element. A number of
      anecdotal reports have shown that TERPs diffuse pain, including chronic,
      inflammatory, and neuropathic. Pain is a very complex biochemical and electrical
      process involving sensory part, nerve transmission, and brain perception of pain.
      We concentrated our research on nerve transmission, which is electrical signal
      along the nerve (axon). This electrical signal is created by a complex activity
      of opening and closing of pain related ion channels and redistribution of
      electrically charged ions on the nerve cell membrane. Ion channels are made of
      different proteins, which are involved with the complex processes of opening and
      closing ion channels. Here, we apply the resonant recognition model to analyze
      ion channel proteins related to the pain transmission in order to find out, how
      imprints and particles within TERPs can interfere with pain related activity of
      ion channels.

PMID- 29364127
TI  - Cooperative Abnormality Detection via Diffusive Molecular Communications.
AB  - In this paper, we consider abnormality detection via diffusive molecular
      communications (MCs) for a network consisting of several sensors and a fusion
      center (FC). If a sensor detects an abnormality, it injects a number of molecules
      into the medium which is proportional to its sensing output. Two transmission
      schemes for releasing molecules into the medium are considered. In the first
      scheme, each sensor releases a different type of molecule (DTM), whereas in the
      second scheme, all sensors release the same type of molecule (STM). The molecules
      released by the sensors propagate through the MC channel and some may reach the
      FC where the final decision regarding whether or not an abnormality has occurred
      is made. We derive the optimal decision rules for both DTM and STM. However, the
      optimal detectors entail high computational complexity as log-likelihood ratios
      (LLRs) have to be computed. To overcome this issue, we show that the optimal
      decision rule for STM can be transformed into an equivalent low-complexity
      decision rule. Since a similar transformation is not possible for DTM, we propose
      simple low-complexity sub-optimal detectors based on different approximations of
      the LLR. The proposed low-complexity detectors are more suitable for practical MC
      systems than the original complex optimal decision rule, particularly when the FC
      is a nano-machine with limited computational capabilities. Furthermore, we
      analyze the performance of the proposed detectors in terms of their false alarm
      and missed detection probabilities. Simulation results verify our analytical
      derivations and reveal interesting insights regarding the tradeoff between
      complexity and performance of the proposed detectors and the considered DTM and
      STM schemes.

PMID- 29364128
TI  - Investigating the Effect of Perinatal Nicotine Exposure on Dopaminergic Neurons
      in the VTA Using miRNA Expression Profiles.
AB  - Maternal smoking during pregnancy is associated with developmental, cognitive,
      and behavioral disorders, including low birth weight, attention deficit
      hyperactivity disorder, learning disabilities, and drug abuse later in life.
      Nicotine activates the reward-driven behavior characteristic of drug abuse.
      Dopaminergic (DA) neurons originating from the ventral tegmental area (VTA) of
      the brain, which are stimulated by nicotine and other stimuli, are widely
      implicated in the natural reward pathway that is known to contribute to
      addiction. In recent years, microRNAs have been implicated in disrupting
      regulatory mechanisms due to their capability of targeting multiple genes and
      thus inducing downstream effects along many pathways. In order to investigate
      miRNA expression of dopaminergic neurons from the VTA, we employed patch clamping
      to identify and harvest both DA and non-DA neurons from rats perinatally exposed
      to nicotine for use in single-cell RT-qPCR. Our data indicated that miR-140-5p
      and miR-140-3p were upregulated in DA neurons; while miR-140-3p and miR-212 were
      differentially expressed in non-DA neurons. A functional enrichment analysis was
      also performed on our miRNA-gene prediction network and predicted that our miRNAs
      target genes involved in drug response and neuroplasticity.

PMID- 29364129
TI  - DNA Chaos Blend to Secure Medical Privacy.
AB  - In this technological era, it is highly essential to protect the digital medical
      data from the fraud and forgery as they are transmitted over the public channel.
      Also with the increased data traffic, it is hard to transmit the entire bulky
      medical data. New methods have come into the scene to reduce the traffic while
      maintaining the sufficient level of security. Partial encryption is one of the
      methods which selectively encrypt the bulky medical image. Meanwhile, if the same
      medical image is needed to be reused for another diagnosis, then it is
      recommended to protect the entire medical image. This paper proposes a hybrid
      encryption scheme based on deoxyribo nucleic acid and chaotic maps, which can be
      adaptable for both selective and full medical image encryption. The proposed
      algorithm uses multiple chaotic maps in single process to generate the highly
      random keys for encrypting the color digital imaging and communications in
      medicine image. The algorithm comprises three phases, namely, permutation,
      encoding, and diffusion. In all the phases, the selection of specific rule set
      depends on the key sequences produced from the combined chaotic system.
      Experimental results are carried out to validate the resistance of the developed
      algorithm toward statistical, differential, and brute force attacks.

PMID- 29364130
TI  - Wireless Optogenetic Nanonetworks for Brain Stimulation: Device Model and
      Charging Protocols.
AB  - In recent years, numerous research efforts have been dedicated toward developing
      efficient implantable devices for brain stimulation. However, there are
      limitations and challenges with the current technologies. They include neuron
      population stimulation instead of single neuron level, the size, the
      biocompatibility, and the device lifetime reliability in the patient's brain. We
      have recently proposed the concept of wireless optogenetic nanonetworking devices
      (WiOptND) that could address the problem of long term deployment, and at the same
      time target single neuron stimulation utilizing ultrasonic as a mode for energy
      harvesting. In addition, a number of charging protocols are also proposed, in
      order to minimize the quantity of energy required for charging, while ensuring
      minimum number of neural spike misfirings. These protocols include the simple
      charge and fire, which requires the full knowledge of the raster plots of neuron
      firing patterns, and the predictive sliding detection window, and its variant
      Markov-chain based time-delay patterns, which minimizes the need for full
      knowledge of neural spiking patterns as well as number of ultrasound charging
      frequencies. Simulation results exhibit a drop for the stimulation ratio of ~ 25%
      and more stable trend in its efficiency ratio (standard deviation of ~0.5%) for
      the Markov-chain based time-delay patterns protocol compared with the baseline
      change and fire. The results show the feasibility of utilizing WiOptND for long
      term implants in the brain, and a new direction toward precise stimulation of
      neurons in the cortical microcolumn of the brain cortex.

PMID- 29364131
TI  - Symbol Synchronization for Diffusion-Based Molecular Communications.
AB  - Symbol synchronization refers to the estimation of the start of a symbol interval
      and is needed for reliable detection. In this paper, we develop several symbol
      synchronization schemes for molecular communication (MC) systems where we
      consider some practical challenges, which have not been addressed in the
      literature yet. In particular, we take into account that in MC systems, the
      transmitter may not be equipped with an internal clock and may not be able to
      emit molecules with a fixed release frequency. Such restrictions hold for
      practical nanotransmitters, e.g., modified cells, where the lengths of the symbol
      intervals may vary due to the inherent randomness in the availability of food and
      energy for molecule generation, the process for molecule production, and the
      release process. To address this issue, we develop two synchronization-detection
      frameworks which both employ two types of molecule. In the first framework, one
      type of molecule is used for symbol synchronization and the other one is used for
      data detection, whereas in the second framework, both types of molecule are used
      for joint symbol synchronization and data detection. For both frameworks, we
      first derive the optimal maximum likelihood (ML) symbol synchronization schemes
      as performance upper bounds. Since ML synchronization entails high complexity,
      for each framework, we also propose three low-complexity suboptimal schemes,
      namely a linear filter-based scheme, a peak observation-based scheme, and a
      threshold-trigger scheme, which are suitable for MC systems with limited
      computational capabilities. Furthermore, we study the relative complexity and the
      constraints associated with the proposed schemes and the impact of the insertion
      and deletion errors that arise due to imperfect synchronization. Our simulation
      results reveal the effectiveness of the proposed synchronization schemes and
      suggest that the end-to-end performance of MC systems significantly depends on
      the accuracy of the symbol synchronization.

PMID- 29364132
TI  - Competitive Spiking Neural P Systems With Rules on Synapses.
AB  - This paper proposes an extension of spiking neural P systems with rules on
      synapses (SNP-RS systems) working in competitive strategy, called competitive SNP
      RS (CSNP-RS systems). In CSNP-RS systems, the spikes are viewed as a kind of
      competitive resources, and the rules on different synapses will compete the
      spikes (resources) in neurons. A new strategy is considered: the total amount of
      spikes consumed by these rules should be greater than or equal to the generated
      amount of spikes. There are two cases to chosen one rule non-deterministically:
      1) two or more rules on the same synapse are enabled; and 2) two or more rules on
      the different synapses are enabled, and the number of spikes contained in neuron
      is smaller than the number of spikes consumed by these rules. CSNP-RS systems are
      a kind of distributed parallel computing models. The computational power of CSNP
      RS systems is investigated. Specifically, we prove that CSNP-RS systems are
      turing universal as number generating/accepting devices and function computing
      device.

PMID- 29364133
TI  - Hierarchy and Assortativity as New Tools for Binding-Affinity Investigation: The
      Case of the TBA Aptamer-Ligand Complex.
AB  - Aptamers are single stranded DNA, RNA, or peptide sequences having the ability to
      bind several specific targets (proteins, molecules as well as ions). Therefore,
      aptamer production and selection for therapeutic and diagnostic applications is
      very challenging. Usually, they are generated in vitro, although computational
      approaches have been recently developed for the in silico production. Despite
      these efforts, the mechanism of aptamer-ligand formation is not completely clear,
      and producing high-affinity aptamers is still quite difficult. This paper aims to
      develop a computational model able to describe aptamer-ligand affinity.
      Topological tools, such as the conventional degree distribution, the rank-degree
      distribution (hierarchy), and the node assortativity are employed. In doing so,
      the macromolecules tertiary-structures are mapped into appropriate graphs. These
      graphs reproduce the main topological features of the macromolecules, by
      preserving the distances between amino acids (nucleotides). Calculations are
      applied to the thrombin binding aptamer (TBA), and the TBA-thrombin complex
      produced in the presence of Na+ or K+. The topological analysis is able to detect
      several differences between complexes obtained in the presence of the two
      cations, as expected by previous investigations. These results support graph
      analysis as a novel computational tool for testing affinity. Otherwise, starting
      from the graphs, an electrical network can be obtained by using the specific
      electrical properties of amino acids and nucleobases. Therefore, a further
      analysis concerns with the electrical response, revealing that the resistance is
      sensitively affected by the presence of sodium or potassium, thus suggesting
      resistance as a useful physical parameter for testing binding affinity.

PMID- 29364134
TI  - CSSTag: Optical Nanoscale Radar and Particle Tracking for In-Body and
      Microfluidic Systems With Vibrating Graphene and Resonance Energy Transfer.
AB  - Biological particle tracking systems monitor cellular processes or particle
      behaviors with the great accuracy. The emissions of fluorescent molecules or
      direct images of particles are captured with cameras or photodetectors. The
      current imaging systems have challenges in detection, collection, and analysis of
      imaging data, penetration depth, and complicated set-ups. In this paper, a
      signaling-based nanoscale acousto-optic radar and microfluidic multiple particle
      tracking (MPT) system is proposed based on the theoretical design providing
      nanoscale optical modulator with vibrating Forster resonance energy transfer and
      vibrating cadmium selenide/zinc sulfide quantum dots (QDs) on graphene
      resonators. The modulator combines significant advantages of graphene membranes
      having wideband resonance frequencies with QDs having broad absorption spectrum
      and tunable properties. The solution denoted by chirp spread spectrum(CSS) Tag
      utilizes classical radar target tracking approaches in nanoscale environments
      based on the capability to generate CSS sequences identifying different bio
      particles. Monte Carlo simulations show significant performance for MPT with a
      modulator of dimension and several picograms of weight, the signal-to-noise ratio
      in the range from -7 to 10 dB, simple light emitting diode sources with power
      less than 4 W/cm2 and high speed tracking for microfluidic environments.

PMID- 29364135
TI  - Towards time-of-flight PET with a semiconductor detector.
AB  - The feasibility of using Cerenkov light, generated by energetic electrons
      following 511 keV photon interactions in the semiconductor TlBr, to obtain fast
      timing information for positron emission tomography (PET) was evaluated. Due to
      its high refractive index, TlBr is a relatively good Cerenkov radiator and with
      its wide bandgap, has good optical transparency across most of the visible
      spectrum. Coupling an SiPM photodetector to a slab of TlBr (TlBr-SiPM) yielded a
      coincidence timing resolution of 620 ps FWHM between the TlBr-SiPM detector and a
      LFS reference detector. This value improved to 430 ps FWHM by applying a high
      pulse amplitude cut based on the TlBr-SiPM and reference detector signal
      amplitudes. These results are the best ever achieved with a semiconductor PET
      detector and already approach the performance required for time-of-flight. As
      TlBr has higher stopping power and better energy resolution than the conventional
      scintillation detectors currently used in PET scanners, a hybrid TlBr-SiPM
      detector with fast timing capability becomes an interesting option for further
      development.

PMID- 29364136
TI  - A framework for directional and higher-order reconstruction in photoacoustic
      tomography.
AB  - Photoacoustic tomography is a hybrid imaging technique that combines high optical
      tissue contrast with high ultrasound resolution. Direct reconstruction methods
      such as filtered back-projection, time reversal and least squares suffer from
      curved line artefacts and blurring, especially in the case of limited angles or
      strong noise. In recent years, there has been great interest in regularised
      iterative methods. These methods employ prior knowledge of the image to provide
      higher quality reconstructions. However, easy comparisons between regularisers
      and their properties are limited, since many tomography implementations heavily
      rely on the specific regulariser chosen. To overcome this bottleneck, we present
      a modular reconstruction framework for photoacoustic tomography, which enables
      easy comparisons between regularisers with different properties, e.g. nonlinear,
      higher-order or directional. We solve the underlying minimisation problem with an
      efficient first-order primal-dual algorithm. Convergence rates are optimised by
      choosing an operator-dependent preconditioning strategy. A variety of
      reconstruction methods are tested on challenging 2D synthetic and experimental
      data sets. They outperform direct reconstruction approaches for strong noise
      levels and limited angle measurements, offering immediate benefits in terms of
      acquisition time and quality. This work provides a basic platform for the
      investigation of future advanced regularisation methods in photoacoustic
      tomography.

PMID- 29364137
TI  - Development of stereotactic radiosurgery using carbon beams (carbon-knife).
AB  - The aim of this research is to develop a stereotactic-radiosurgery (SRS)
      technique using carbon beams to treat small intracranial lesions; we call this
      device the carbon knife. A 2D-scanning method is adapted to broaden a pencil beam
      to an appropriate size for an irradiation field. A Mitsubishi slow extraction
      using third order resonance through a rf acceleration system stabilized by a feed
      forward scanning beam using steering magnets with a 290 MeV/u initial beam energy
      was used for this purpose. Ridge filters for spread-out Bragg peaks (SOBPs) with
      widths of 5 mm, 7.5 mm, and 10 mm were designed to include fluence-attenuation
      effects. The collimator, which defines field shape, was used to reduce the
      lateral penumbra. The lateral-penumbra width at the SOBP region was less than 2
      mm for the carbon knife. The penumbras behaved almost the same when changing the
      air gap, but on the other hand, increasing the range-shifter thickness mostly
      broadened the lateral penumbra. The physical-dose rates were approximate 6 Gy s-1
      and 4.5 Gy s-1 for the 10  *  10 mm2 and 5  *  5 mm2 collimators, respectively.

PMID- 29364138
TI  - Locally adaptive decision in detection of clustered microcalcifications in
      mammograms.
AB  - In computer-aided detection or diagnosis of clustered microcalcifications (MCs)
      in mammograms, the performance often suffers from not only the presence of false
      positives (FPs) among the detected individual MCs but also large variability in
      detection accuracy among different cases. To address this issue, we investigate a
      locally adaptive decision scheme in MC detection by exploiting the noise
      characteristics in a lesion area. Instead of developing a new MC detector, we
      propose a decision scheme on how to best decide whether a detected object is an
      MC or not in the detector output. We formulate the individual MCs as statistical
      outliers compared to the many noisy detections in a lesion area so as to account
      for the local image characteristics. To identify the MCs, we first consider a
      parametric method for outlier detection, the Mahalanobis distance detector, which
      is based on a multi-dimensional Gaussian distribution on the noisy detections. We
      also consider a non-parametric method which is based on a stochastic neighbor
      graph model of the detected objects. We demonstrated the proposed decision
      approach with two existing MC detectors on a set of 188 full-field digital
      mammograms (95 cases). The results, evaluated using free response operating
      characteristic (FROC) analysis, showed a significant improvement in detection
      accuracy by the proposed outlier decision approach over traditional thresholding
      (the partial area under the FROC curve increased from 3.95 to 4.25, p-value  <10
      4). There was also a reduction in case-to-case variability in detected FPs at a
      given sensitivity level. The proposed adaptive decision approach could not only
      reduce the number of FPs in detected MCs but also improve case-to-case
      consistency in detection.

PMID- 29364140
TI  - Xeniaphyllane-Derived Terpenoids from Soft Coral Sinularia nanolobata.
AB  - A novel tetranorditerpenoid, sinubatin A (1) (having an unprecedented carbon
      skeleton), a new norditerpenoid, sinubatin B (2) (a 4,5-epoxycaryophyllene
      possessing an unusual methylfuran moiety side chain), and a known diterpenoid,
      gibberosin J (3) were isolated from soft coral Sinulariananolobata. The
      structures of the new compounds were elucidated by extensive analysis of
      spectroscopic data.

PMID- 29364139
TI  - The Differentiation of Rat Oligodendroglial Cells Is Highly Influenced by the
      Oxygen Tension: In Vitro Model Mimicking Physiologically Normoxic Conditions.
AB  - Oligodendrocyte progenitor cells (OPCs) constitute one of the main populations of
      dividing cells in the central nervous system (CNS). Physiologically, OPCs give
      rise to mature, myelinating oligodendrocytes and confer trophic support to their
      neighboring cells within the nervous tissue. OPCs are known to be extremely
      sensitive to the influence of exogenous clues which might affect their crucial
      biological processes, like survival, proliferation, differentiation, and the
      ability to generate a myelin membrane. Alterations in their differentiation
      influencing their final potential for myelinogenesis are usually the leading
      cause of CNS dys- and demyelination, contributing to the development of
      leukodystrophic disorders. The evaluation of the mechanisms that cause
      oligodendrocytes to malfunction requires detailed studies based on designed in
      vitro models. Since OPCs readily respond to changes in local homeostasis, it is
      crucial to establish restricted culture conditions to eliminate the potential
      stimuli that might influence oligodendrocyte biology. Additionally, the in vitro
      settings should mimic the physiological conditions to enable the obtained results
      to be translated to future preclinical studies. Therefore, the aim of our study
      was to investigate OPC differentiation in physiological normoxia (5% O2) and a
      restricted in vitro microenvironment. To evaluate the impact of the combined
      microenvironmental clues derived from other components of the nervous tissue,
      which are also influenced by the local oxygen concentration, the process of
      generating OPCs was additionally analyzed in organotypic hippocampal slices. The
      obtained results show that OPC differentiation, although significantly slowed
      down, proceeded correctly through its typical stages in the physiologically
      relevant conditions created in vitro. The established settings were also
      conducive to efficient cell proliferation, exerting also a neuroprotective effect
      by promoting the proliferation of neurons. In conclusion, the performed studies
      show how oxygen tension influences OPC proliferation, differentiation, and their
      ability to express myelin components, and should be taken into consideration
      while planning preclinical studies, e.g., to examine neurotoxic compounds or to
      test neuroprotective strategies.

PMID- 29364141
TI  - Visualization and Quantitative 3D Analysis of Intraocular Melanoma and Its
      Vascularization in a Hamster Eye.
AB  - A tumor vasculature network undergoes intense growth and rebuilding during tumor
      growth. Traditionally, vascular networks are histologically examined using
      parameters such as vessel density determined from two-dimensional slices of the
      tumor. Two-dimensional probing of a complicated three-dimensional (3D) structure
      only provides partial information. Therefore, we propose the use of microcomputed
      tomography (micro-CT) imaging to analyze the evolution of a tumor vasculature in
      an experimental ocular tumor model. A Bomirski Hamster Melanoma was implanted in
      the anterior chamber of a hamster eye. Ultrasound (US) imaging of the same tumor
      was performed in vivo, and the vascular results obtained using the two methods
      were compared. Normal ocular tissues, a tumor, and a tumor vascular structure
      were revealed with high accuracy using micro-CT. The vessels that grew within the
      tumor were chaotic, leaky, and contained many convoluted micro-vessels and
      embolizations. They comprised 20-38% of the tumor mass. The blood flow in the
      larger functional vessels was in the range from 10 to 25 mm/s, as determined by
      in vivo Doppler US. The micro-CT imaging of the hamster eyeball enabled both
      qualitative and quantitative 3D analyses of the globe at a histological level.
      Although the presented images were obtained ex vivo, micro-CT noninvasive imaging
      is being developed intensively, and high-resolution in vivo imaging is feasible.

PMID- 29364143
TI  - Unveiling a Selective Mechanism for the Inhibition of alpha-Synuclein Aggregation
      by beta-Synuclein.
AB  - alpha-Synuclein (alphaS) is an intrinsically disordered protein that is
      associated with Parkinson's disease (PD) through its ability to self-assemble
      into oligomers and fibrils. Inhibition of this oligomerization cascade is an
      interesting approach to developing therapeutical strategies and beta-synuclein
      (betaS) has been described as a natural negative regulator of this process.
      However, the biological background and molecular mechanisms by which this
      inhibition occurs is unclear. Herein, we focused on assessing the effect of betaS
      on the aggregation of five alphaS pathological mutants linked to early-onset PD
      (A30P, E46K, H50Q, G51D and A53T). By coupling single molecule fluorescence
      spectroscopy to a cell-free protein expression system, we validated the ability
      of betaS to act as a chaperone of alphaS, effectively inhibiting its aggregation.
      Interestingly, we found that betaS does so in a selective manner, i.e., is a more
      effective inhibitor for certain alphaS pathological mutants-A30P and G51D-as
      compared to E46K, H50Q and A53T. Moreover, two-color coincidence experiments
      proved that this discrepancy is due to a preferential incorporation of betaS into
      smaller oligomers of alphaS. This was validated by showing that the chaperoning
      effect was lost when proteins were mixed after being expressed individually. This
      study highlights the potential of fluorescence spectroscopy to deconstruct alphaS
      aggregation cascade and its interplay with betaS.

PMID- 29364144
TI  - A Facile Route toward the Increase of Oxygen Content in Nanosized Zeolite by
      Insertion of Cerium and Fluorinated Compounds.
AB  - Enriching oxygen content within nanosized zeolite X (as synthesized Na-X) by
      insertion of cerium (ion exchanged Ce-X) and functionalization with
      bromoperfluoro-n-octane (fluorinated F-X) is reported. The materials were fully
      characterized by powder X-ray diffraction (XRD), dynamic light scattering (DLS),
      zeta potential, thermogravimetric analysis (TGA), nitrogen adsorption, and
      nuclear magnetic resonance (19F NMR). The O2 adsorption in the zeolite samples at
      various concentrations (0 to 165 Torr) at -196  degrees C was studied by in situ
      FTIR. The modification of nanosized zeolites did not alter their colloidal
      stability, crystallinity, porosity, and particle size distribution. The inclusion
      of cerium and bromoperfluoro-n-octane considerably increase the oxygen capacity
      by 33% for samples Ce-X and F-X in comparison to the as-synthesized Na-X zeolite.
      Further, toxicity tests revealed that these materials are safe, which opens the
      door for their implementation in medical applications, where controlled delivery
      of oxygen is highly desirable.

PMID- 29364142
TI  - Current Perspectives of Telomerase Structure and Function in Eukaryotes with
      Emerging Views on Telomerase in Human Parasites.
AB  - Replicative capacity of a cell is strongly correlated with telomere length
      regulation. Aberrant lengthening or reduction in the length of telomeres can lead
      to health anomalies, such as cancer or premature aging. Telomerase is a master
      regulator for maintaining replicative potential in most eukaryotic cells. It does
      so by controlling telomere length at chromosome ends. Akin to cancer cells, most
      single-cell eukaryotic pathogens are highly proliferative and require persistent
      telomerase activity to maintain constant length of telomere and propagation
      within their host. Although telomerase is key to unlimited cellular proliferation
      in both cases, not much was known about the role of telomerase in human parasites
      (malaria, Trypanosoma, etc.) until recently. Since telomerase regulation is
      mediated via its own structural components, interactions with catalytic reverse
      transcriptase and several factors that can recruit and assemble telomerase to
      telomeres in a cell cycle-dependent manner, we compare and discuss here recent
      findings in telomerase biology in cancer, aging and parasitic diseases to give a
      broader perspective of telomerase function in human diseases.

PMID- 29364146
TI  - The Enhanced Intramolecular Energy Transfer and Strengthened ff Luminescence of a
      Stable Helical Eu Complex in Ionic Liquids.
AB  - The luminescence of a Eu complex (EuL) is enhanced by stabilization of the
      coordination structure in highly viscous ionic liquids. The EuL was found to
      maintain a stable single helical structure both in organic solvents and in the
      ionic liquids [BMIM][PF6] and [EMIM][PF6]. A colorless solution of EuL dissolved
      in [BMIM][PF6] exhibits bright red luminescence with a quantum yield of 32.3%, a
      value that is much higher than that in acetonitrile (12%). Estimated rate
      constants for the energy relaxation pathway indicate that the energy transfer
      efficiency is enhanced in [BMIM][PF6] as a result of the suppression of molecular
      fluctuations in the ligands. Additionally, a highly luminescent helical structure
      is preserved in [EMIM][PF6] up to 120  degrees C.

PMID- 29364147
TI  - Marine Compounds and Cancer: 2017 Updates.
AB  - By the end of 2017, there were seven marine-derived pharmaceutical substances
      that have been approved by the FDA for clinical use as drugs[...].

PMID- 29364145
TI  - Lignins: Biosynthesis and Biological Functions in Plants.
AB  - Lignin is one of the main components of plant cell wall and it is a natural
      phenolic polymer with high molecular weight, complex composition and structure.
      Lignin biosynthesis extensively contributes to plant growth, tissue/organ
      development, lodging resistance and the responses to a variety of biotic and
      abiotic stresses. In the present review, we systematically introduce the
      biosynthesis of lignin and its regulation by genetic modification and summarize
      the main biological functions of lignin in plants and their applications. We hope
      this review will give an in-depth understanding of the important roles of lignin
      biosynthesis in various plants' biological processes and provide a theoretical
      basis for the genetic improvement of lignin content and composition in energy
      plants and crops.

PMID- 29364148
TI  - Indole-3-Carbonitriles as DYRK1A Inhibitors by Fragment-Based Drug Design.
AB  - Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a
      potential drug target because of its role in the development of Down syndrome and
      Alzheimer's disease. The selective DYRK1A inhibitor 10-iodo-11H-indolo[3,2
      c]quinoline-6-carboxylic acid (KuFal194), a large, flat and lipophilic molecule,
      suffers from poor water solubility, limiting its use as chemical probe in
      cellular assays and animal models. Based on the structure of KuFal194, 7-chloro
      1H-indole-3-carbonitrile was selected as fragment template for the development of
      smaller and less lipophilic DYRK1A inhibitors. By modification of this fragment,
      a series of indole-3-carbonitriles was designed and evaluated as potential DYRK1A
      ligands by molecular docking studies. Synthesis and in vitro assays on DYRK1A and
      related protein kinases identified novel double-digit nanomolar inhibitors with
      submicromolar activity in cell culture assays.

PMID- 29364149
TI  - Exploring Genomic Variants Related to Residual Feed Intake in Local and
      Commercial Chickens by Whole Genomic Resequencing.
AB  - Improving feed efficiency is a major goal in poultry production to reduce
      production costs and increase profitability. The genomic variants and possible
      molecular mechanisms responsible for residual feed intake (RFI) in chickens,
      however, remain poorly understood. In this study, using both local and commercial
      breeds, genome re-sequencing of low RFI and high RFI chickens was performed to
      elucidate the genomic variants underlying RFI. Results showed that 8,505,214 and
      8,479,041 single nucleotide polymorphisms (SNPs) were detected in low and high
      RFI Beijing-You chickens, respectively; 8,352,008 and 8,372,769 SNPs were
      detected in low- and high-RFI Cobb chickens, respectively. Through a series of
      filtering processes, 3746 candidate SNPs assigned to 1137 genes in Beijing-You
      chickens and 575 candidate SNPs (448 genes) in Cobb chickens were found. The
      validation of the selected 191 SNPs showed that 46 SNPs were significantly
      associated with the RFI in an independent population of 779 Cobb chickens,
      suggesting that the method of screening associated SNPs with whole genome
      sequencing (WGS) strategy was reasonable. Functions annotation of RFI-related
      genes indicated that genes in Beijing-You were enriched in lipid and carbohydrate
      metabolism, as well as the phosphatase and tensin homolog (PTEN) signaling
      pathway. In Cobb, however, RFI-related genes were enriched in the feed behavior
      process and cAMP responsive element binding protein (CREB) signaling pathway. For
      both breeds, organismal development physiological processes were enriched.
      Correspondingly, NOS1, PHKG1, NEU3 and PIP5K1B were differentially expressed in
      Beijing-You, while CDC42, CSK, PIK3R3, CAMK4 and PLCB4 were differentially
      expressed in Cobb, suggesting that these might be key genes that contribute to
      RFI. The results of the present study identified numerous novel SNPs for RFI,
      which provide candidate biomarkers for use in the genetic selection for RFI. The
      study has improved knowledge of the genomic variants and potential biological
      pathways underlying RFI in chickens.

PMID- 29364150
TI  - Molecular Imprinting and Functional Polymers for All Transducers and
      Applications.
AB  - The main challenge in developing a chemical sensor is the synthesis of
      recognition coatings, which are very sensitive and selective to analytes of
      interest. Molecular imprinting has proven to be the most innovative strategy for
      this purpose in functional polymer design in the last few decades. Moreover, the
      introduction of functional groups brings about new applications for all available
      transducers. Sensitivity and selectivity features of sensor coatings can be tuned
      by this approach. The strategy produces molecular cavities and interaction sites
      in sensor coatings. The synthesis of these tailored recognition materials is
      performed in an outstanding manner, saving time and the high costs of chemicals.
      Furthermore, intermolecular interactions between the analyte and chemical layers
      will generate sites that are complementary to the analyte. This procedure can
      easily be done, directly on a transducer surface, which entails engulfing the
      analyte by a prepolymer and crosslinking the polymeric material. These imprinted
      polymers form a robust recognition layer on the transducer surface, which cannot
      be peeled off and can withstand very harsh conditions, both in gaseous and liquid
      media. These recognition materials are very suitable, for small molecules and
      even large bioparticles.

PMID- 29364153
TI  - Paper-Based Electrochemical Detection of Chlorate.
AB  - We describe the use of a paper-based probe impregnated with a vanadium-containing
      polyoxometalate anion, [PMo11VO40]5-, on screen-printed carbon electrodes for the
      electrochemical determination of chlorate. Cyclic voltammetry (CV) and
      chronocoulometry were used to characterize the ClO3- response in a pH = 2.5
      solution of 100 mM sodium acetate. A linear CV current response was observed
      between 0.156 and 1.25 mg/mL with a detection limit of 0.083 mg/mL (S/N > 3).
      This performance was reproducible using [PMo11VO40]5--impregnated filter paper
      stored under ambient conditions for as long as 8 months prior to use. At high
      concentration of chlorate, an additional catalytic cathodic peak was seen in the
      reverse scan of the CVs, which was digitally simulated using a simple model. For
      chronocoulometry, the charge measured after 5 min gave a linear response from
      0.625 to 2.5 mg/mL with a detection limit of 0.31 mg/mL (S/N > 3). In addition,
      the slope of charge vs. time also gave a linear response. In this case the linear
      range was from 0.312 to 2.5 mg/mL with a detection limit of 0.15 mg/mL (S/N > 3).
      Simple assays were conducted using three types of soil, and recovery measurements
      reported.

PMID- 29364152
TI  - Metabolite Profiling of 14 Wuyi Rock Tea Cultivars Using UPLC-QTOF MS and UPLC
      QqQ MS Combined with Chemometrics.
AB  - Wuyi Rock tea, well-recognized for rich flavor and long-lasting fragrance, is a
      premium subcategory of oolong tea mainly produced in Wuyi Mountain and nearby
      regions of China. The quality of tea is mainly determined by the chemical
      constituents in the tea leaves. However, this remains underexplored for Wuyi Rock
      tea cultivars. In this study, we investigated the leaf metabolite profiles of 14
      major Wuyi Rock tea cultivars grown in the same producing region using UPLC-QTOF
      MS and UPLC-QqQ MS with data processing via principal component analysis and
      cluster analysis. Relative quantitation of 49 major metabolites including flavan
      3-ols, proanthocyanidins, flavonol glycosides, flavone glycosides, flavonone
      glycosides, phenolic acid derivatives, hydrolysable tannins, alkaloids and amino
      acids revealed clear variations between tea cultivars. In particular, catechins,
      kaempferol and quercetin derivatives were key metabolites responsible for
      cultivar discrimination. Information on the varietal differences in the levels of
      bioactive/functional metabolites, such as methylated catechins, flavonol
      glycosides and theanine, offers valuable insights to further explore the
      nutritional values and sensory qualities of Wuyi Rock tea. It also provides
      potential markers for tea plant fingerprinting and cultivar identification.

PMID- 29364154
TI  - Parental Attitudes, Behaviors, and Barriers to School Readiness among Parents of
      Low-Income Latino Children.
AB  - We sought to explore parental attitudes, behaviors, and barriers regarding school
      readiness in a county clinic serving low income, Latino children. Between
      December 2013-September 2014, we conducted a cross sectional survey of parents
      during 3-6 years well-child appointments about school readiness (SR) across: (1)
      attitudes/behaviors; (2) barriers; and (3) awareness; and (4) use of local
      resources. Most parents (n = 210, response rate 95.6%) find it very
      important/important for their child to know specific skills prior to school: take
      turns and share (98.5%), use a pencil and count (97.6%), know letters (99.1%),
      colors (97.1%), and shapes (96.1%). Over 80% of parents find education important
      and engage in positive SR behaviors: singing, practicing letters, or reading.
      Major barriers to SR were lack of knowledge for kindergarten readiness, language
      barriers, access to books at home, constraints on nightly reading, difficulty
      completing school forms, and limited free time with child. Awareness of local
      resources such as preschool programs was higher than actual utilization. These
      low-income, Latino parents value SR but lack knowledge to prepare their child for
      school and underutilize community resources such as free preschool programs.
      Pediatricians are uniquely positioned to address these needs, but more evidence
      based interventions are needed.

PMID- 29364155
TI  - An in Vitro Study on the Effect of Combined Treatment with Photodynamic and
      Chemical Therapies on Candida albicans.
AB  - Candida albicans is the most commonly encountered human fungal pathogen, and it
      is traditionally treated with antimicrobial chemical agents. The antimicrobial
      effect of these agents is largely weakened by drug resistance and biofilm
      associated virulence. Enhancement of the antimicrobial activity of existing
      agents is needed for effective candidiasis treatment. Our aim was to develop a
      therapy that combined biofilm disruption with existing antimicrobial agents.
      Photodynamic therapy (PDT) utilizing curcumin and blue light was tested as an
      independent therapy and in combination with fluconazole treatment. Viability
      assays and morphology analysis were used to assess the effectiveness of C.
      albicans treatment. Results showed that fluconazole treatment decreased the
      viability of planktonic C. albicans, but the decrease was not as pronounced in
      adherent C. albicans because its biofilm form was markedly more resistant to the
      antimicrobiotic. PDT effectively eradicated C. albicans biofilms, and when
      combined with fluconazole, PDT significantly inhibited C. albicans to a greater
      extent. This study suggests that the addition of PDT to fluconazole to treat C.
      albicans infection enhances its effectiveness and can potentially be used
      clinically.

PMID- 29364156
TI  - Use of an UHPLC-MS/MS Method for Determination of Kuraridin and Characterization
      of Its Metabolites in Rat Plasma after Oral Administration.
AB  - Kuraridin is an active natural prenylated flavonoid ingredient originating from
      the well-known traditional Chinese medicine Sophora flavescens Ait., that
      possesses various bioactivities, such as antitumor activity, PLCgamma1 inhibitory
      activity, glycosidase inhibitory activity, etc. However, there is no report on
      the plasma metabolic profile and pharmacokinetic study of kuraridin. The current
      study was designed to use an ultra-performance liquid chromatography/tandem mass
      spectrometry (UHPLC-MS/MS) method for the quantification and characterization
      metabolites in rat plasma after oral administration of kuraridin. A liquid-liquid
      extraction method with ethyl acetate-acetonitrile (1:3) was used to extract the
      kuraridin from rat plasma samples. The chromatographic separation was carried out
      on a Hypersil GOLD UHPLC C18 column equipped with a C18 guard cartridge using a
      gradient elution with organic solvent-water as mobile phase. Based on comparing
      the retention times with reference standards or on the basis of MS2 fragmentation
      behaviors, a total of 19 metabolites were identified or tentatively characterized
      from rat plasma. Under the optimized conditions, the method showed good linearity
      (r2 > 0.99) over the ranges of 1-500 ng/mL for kuraridin. The inter- and intra
      day precisions were less than 8.95%, and the accuracy was in the range of -6.27
      6.48%. The recovery of kuraridin ranged from 90.1% to 100.4%. The developed UHPLC
      MS/MS method was thus successfully applied in the qualitative of metabolites and
      quantitative analysis of kuraridin in rat plasma.

PMID- 29364157
TI  - Solid Lipid Nanoparticles Carrying Temozolomide for Melanoma Treatment.
      Preliminary In Vitro and In Vivo Studies.
AB  - AIM: To develop an innovative delivery system for temozolomide (TMZ) in solid
      lipid nanoparticles (SLN), which has been preliminarily investigated for the
      treatment of melanoma. MATERIALS AND METHODS: SLN-TMZ was obtained through fatty
      acid coacervation. Its pharmacological effects were assessed and compared with
      free TMZ in in vitro and in vivo models of melanoma and glioblastoma. RESULTS:
      Compared to the standard free TMZ, SLN-TMZ exerted larger effects, when cell
      proliferation of melanoma cells, and neoangiogeneis were evaluated. SLN-TMZ also
      inhibited growth and vascularization of B16-F10 melanoma in C57/BL6 mice, without
      apparent toxic effects. CONCLUSION: SLN could be a promising strategy for the
      delivery of TMZ, allowing an increased stability of the drug and thereby its
      employment in the treatment of aggressive malignacies.

PMID- 29364151
TI  - Insights into the Molecular Mechanisms of Alzheimer's and Parkinson's Diseases
      with Molecular Simulations: Understanding the Roles of Artificial and
      Pathological Missense Mutations in Intrinsically Disordered Proteins Related to
      Pathology.
AB  - Amyloid-beta and alpha-synuclein are intrinsically disordered proteins (IDPs),
      which are at the center of Alzheimer's and Parkinson's disease pathologies,
      respectively. These IDPs are extremely flexible and do not adopt stable
      structures. Furthermore, both amyloid-beta and alpha-synuclein can form toxic
      oligomers, amyloid fibrils and other type of aggregates in Alzheimer's and
      Parkinson's diseases. Experimentalists face challenges in investigating the
      structures and thermodynamic properties of these IDPs in their monomeric and
      oligomeric forms due to the rapid conformational changes, fast aggregation
      processes and strong solvent effects. Classical molecular dynamics simulations
      complement experiments and provide structural information at the atomic level
      with dynamics without facing the same experimental limitations. Artificial
      missense mutations are employed experimentally and computationally for providing
      insights into the structure-function relationships of amyloid-beta and alpha
      synuclein in relation to the pathologies of Alzheimer's and Parkinson's diseases.
      Furthermore, there are several natural genetic variations that play a role in the
      pathogenesis of familial cases of Alzheimer's and Parkinson's diseases, which are
      related to specific genetic defects inherited in dominant or recessive patterns.
      The present review summarizes the current understanding of monomeric and
      oligomeric forms of amyloid-beta and alpha-synuclein, as well as the impacts of
      artificial and pathological missense mutations on the structural ensembles of
      these IDPs using molecular dynamics simulations. We also emphasize the recent
      investigations on residual secondary structure formation in dynamic
      conformational ensembles of amyloid-beta and alpha-synuclein, such as beta
      structure linked to the oligomerization and fibrillation mechanisms related to
      the pathologies of Alzheimer's and Parkinson's diseases. This information
      represents an important foundation for the successful and efficient drug design
      studies.

PMID- 29364158
TI  - The Prevalence of Helicobacter pylori in Estonian Bariatric Surgery Patients.
AB  - Helicobacter pylori (Hp) is one of the most important human pathogens that can
      cause duodenal and gastric ulcers, gastritis and stomach cancer. Hp infection is
      considered to be a cause of limiting access to bariatric surgery. The aim of this
      study was to determine the prevalence of Hp in patients with obesity going into
      bariatric surgery and to reveal the relationship between Hp and clinical data.
      The study group was formed of 68 preoperative bariatric surgery patients (body
      mass index (BMI) 44.7 +/- 4.8). Gastric biopsies (antrum and corpus) were used
      for histological and molecular (caqA and glmM genes) examinations. The PCR method
      revealed Hp infection in 64.7% of obese patients that is higher in comparison
      with histological analysis (55.9%). The prevalence of cagA and glmM genes in
      antrum mucosa was 45.6% and 47.0% while in the corpus it was 41.2% and 38.3%,
      respectively. The coincidence of both cagA and glmM virulence genes in the antrum
      and corpus mucosa was 33.8% and 22.1%, respectively. Either of the genes was
      found in 58.8% of antrum and 57.3% of corpus mucosa. Presence of caqA and glmM
      genes was in association with active and atrophic chronic gastritis. In
      conclusion, our study demonstrated that two thirds of morbidly obese patients
      undergoing bariatric surgery are infected with Hp and have a high prevalence of
      cagA and glmM virulence genes that points out the necessity for diagnostics and
      treatment of this infection before surgery.

PMID- 29364160
TI  - Regenerative, Highly-Sensitive, Non-Enzymatic Dopamine Sensor and Impact of
      Different Buffer Systems in Dopamine Sensing.
AB  - Carbon nanotube field-effect transistors are used extensively in ultra-sensitive
      biomolecule sensing applications. Along with high sensitivity, the possibility of
      regeneration is highly desired in bio-sensors. An important constituent of such
      bio-sensing systems is the buffer used to maintain pH and provide an ionic
      conducting medium, among its other properties. In this work, we demonstrate
      highly-sensitive regenerative dopamine sensors and the impact of varying buffer
      composition and type on the electrolyte gated field effect sensors. The role of
      the buffer system is an often ignored condition in the electrical
      characterization of sensors. Non-enzymatic dopamine sensors are fabricated and
      regenerated in hydrochloric acid (HCl) solution. The sensors are finally measured
      against four different buffer solutions. The impact of the nature and chemical
      structure of buffer molecules on the dopamine sensors is shown, and the
      appropriate buffer systems are demonstrated.

PMID- 29364159
TI  - Elucidating the Role of CD84 and AHR in Modulation of LPS-Induced Cytokines
      Production by Cruciferous Vegetable-Derived Compounds Indole-3-Carbinol and 3,3'
      Diindolylmethane.
AB  - Modulation of the immune system by cancer protective food bioactives has
      preventive and therapeutic importance in prostate cancer, but the mechanisms
      remain largely unclear. The current study tests the hypothesis that the diet
      derived cancer protective compounds, indole-3-carbinol (I3C) and 3,3'
      diindolylmethane (DIM), affect the tumor microenvironment by regulation of
      inflammatory responses in monocytes and macrophages. We also ask whether I3C and
      DIM act through the aryl hydrocarbon (AHR)-dependent pathway or the signaling
      lymphocyte activation molecule (SLAM) family protein CD84-mediated pathway. The
      effect of I3C and DIM was examined using the human THP-1 monocytic cell in its un
      differentiated (monocyte) and differentiated (macrophage) state. We observed that
      I3C and DIM inhibited lipopolysaccharide (LPS) induction of IL-1beta mRNA and
      protein in the monocyte form but not the macrophage form of THP-1. Interestingly,
      CD84 mRNA but not protein was inhibited by I3C and DIM. AHR siRNA knockdown
      experiments confirmed that the inhibitory effects of I3C and DIM on IL-1beta as
      well as CD84 mRNA are regulated through AHR-mediated pathways. Additionally, the
      AHR ligand appeared to differentially regulate other LPS-induced cytokines
      expression. Hence, cross-talk between AHR and inflammation-mediated pathways, but
      not CD84-mediated pathways, in monocytes but not macrophages may contribute to
      the modulation of tumor environments by I3C and DIM in prostate cancer.

PMID- 29364161
TI  - The Electronic Structure and Optical Properties of Anatase TiO2 with Rare Earth
      Metal Dopants from First-Principles Calculations.
AB  - The electronic and optical properties of the rare earth metal atom-doped anatase
      TiO2 have been investigated systematically via density functional theory
      calculations. The results show that TiO2 doped by Ce or Pr is the optimal choice
      because of its small band gap and strong optical absorption. Rare earth metal
      atom doping induces several impurity states that tune the location of valence and
      conduction bands and an obvious lattice distortion that should reduce the
      probability of electron-hole recombination. This effect of band change originates
      from the 4f electrons of the rare earth metal atoms, which leads to an improved
      visible light absorption. This finding indicates that the electronic structure of
      anatase TiO2 is tuned by the introduction of impurity atoms.

PMID- 29364162
TI  - Metabolic Syndrome and Chronic Renal Disease.
AB  - : Background: The influence of metabolic syndrome (MetS) on kidneys is related to
      many complications. We aimed to assess the association between MetS and chronic
      renal disease defined by a poor estimated glomerular filtration rate (eGFR)
      and/or the presence of microalbuminuria/macroalbuminuria. METHODS: 149 patients
      (77 males/72 females) were enrolled in the study. Chronic renal disease was
      defined according to KDIGO 2012 criteria based on eGFR category and classified
      albuminuria. MetS was studied as a dichotomous variable (0 to 5 components)
      including hypertension, waist circumference, low HDL-cholesterol, high
      triglycerides, and high glucose. Results: The association between clustering MetS
      and both classified eGFR and classified albuminuria (x2 = 50.3, p = 0.001 and x2
      = 26.9, p = 0.003 respectively) was found to be significant. The MetS presence
      showed an odds 5.3-fold (1.6-17.8) higher for low eGFR and 3.2-fold (1.2-8.8)
      higher for albuminuria in combination with the presence of diabetes mellitus,
      which also increased the risk for albuminuria by 3.5-fold (1.1-11.3). Albuminuria
      was significantly associated with high triglycerides, hypertension, high glucose
      (x2 = 11.8, p = 0.003, x2 = 11.4, p = 0.003 and x2 = 9.1, p = 0.01 respectively),
      and it was mildly associated with a low HDL-C (x2 = 5.7, p = 0.06). A significant
      association between classified eGFR and both high triglycerides and hypertension
      (x2 = 9.7, p = 0.04 and x2 = 16.1, p = 0.003 respectively) was found. Conclusion:
      The clustering of MetS was significantly associated with chronic renal disease
      defined by both classified eGFR and albuminuria. The definition of impaired renal
      function by classified albuminuria was associated with more MetS components
      rather than the evaluation of eGFR category. MetS may contribute to the
      manifestation of albuminuria in patients with diabetes mellitus.

PMID- 29364164
TI  - Thermochemical Stability and Friction Properties of Soft Organosilica Networks
      for Solid Lubrication.
AB  - In view of their possible application as high temperature solid lubricants, the
      tribological and thermochemical properties of several organosilica networks were
      investigated over a range of temperatures between 25 and 580  degrees C.
      Organosilica networks, obtained from monomers with terminal and bridging organic
      groups, were synthesized by a sol-gel process. The influence of carbon content,
      crosslink density, rotational freedom of incorporated hydrocarbon groups, and
      network connectivity on the high temperature friction properties of the polymer
      was studied for condensed materials from silicon alkoxide precursors with
      terminating organic groups, i.e., methyltrimethoxysilane, propyltrimethoxysilane,
      diisopropyldimethoxysilane, cyclohexyltrimethoxysilane, phenyltrimethoxysilane
      and 4-biphenylyltriethoxysilane networks, as well as precursors with organic
      bridging groups between Si centers, i.e., 1,4-bis(triethoxysilyl)benzene and 4,4'
      bis(triethoxysilyl)-1,1'-biphenyl. Pin-on-disc measurements were performed using
      all selected solid lubricants. It was found that materials obtained from
      phenyltrimethoxysilane and cyclohexyltrimethoxysilane precursors showed softening
      above 120  degrees C and performed best in terms of friction reduction, reaching
      friction coefficients as low as 0.01. This value is lower than that of graphite
      films (0.050 +/- 0.005), a common bench mark for solid lubricants.

PMID- 29364163
TI  - Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T
      Cells (CAR-Ts): Combination or Built-In CAR-T.
AB  - Chimeric antigen receptor (CAR) T cell therapy represents the first U.S. Food and
      Drug Administration approved gene therapy and these engineered cells function
      with unprecedented efficacy in the treatment of refractory CD19 positive
      hematologic malignancies. CAR translation to solid tumors is also being actively
      investigated; however, efficacy to date has been variable due to tumor-evolved
      mechanisms that inhibit local immune cell activity. To bolster the potency of CAR
      T cells, modulation of the immunosuppressive tumor microenvironment with immune
      checkpoint blockade is a promising strategy. The impact of this approach on
      hematological malignancies is in its infancy, and in this review we discuss CAR-T
      cells and their synergy with immune-checkpoint blockade.

PMID- 29364165
TI  - Fabrication of Titanium-Niobium-Zirconium-Tantalium Alloy (TNZT) Bioimplant
      Components with Controllable Porosity by Spark Plasma Sintering.
AB  - Spark Plasma Sintering (SPS) is used to fabricate Titanium-Niobium-Zirconium
      Tantalum alloy (TNZT) powder-based bioimplant components with controllable
      porosity. The developed densification maps show the effects of final SPS
      temperature, pressure, holding time, and initial particle size on final sample
      relative density. Correlations between the final sample density and mechanical
      properties of the fabricated TNZT components are also investigated and
      microstructural analysis of the processed material is conducted. A densification
      model is proposed and used to calculate the TNZT alloy creep activation energy.
      The obtained experimental data can be utilized for the optimized fabrication of
      TNZT components with specific microstructural and mechanical properties suitable
      for biomedical applications.

PMID- 29364166
TI  - A Cross-Sectional Study of Viral Hepatitis Perception among Residents from
      Southeast and North Regions of Brazil.
AB  - Few data are available regarding viral hepatitis perception among the general
      global population. The present study aims to estimate the perception of viral
      hepatitis in a cohort of individuals living in two geographical regions of
      Brazil: North (Manaus city (MA)) and Southeast (Rio de Janeiro city (RJ)). A
      cross-sectional, descriptive study was carried out among 287 subjects recruited
      in MA (134) and RJ (153). All individuals answered a questionnaire assessing
      socio-demographic characteristics and viral hepatitis awareness. Participants'
      responses were scored and divided using interquartile values. Associations
      between socio-demographic characteristics and knowledge were also evaluated.
      Interquartile analysis scored 0-21 correct answers as "Very Weak"; 22-27 as
      "Weak"; 28-31 as "Intermediate"; and 32-47 as "Desirable". Mean +/- standard
      deviations (SD) of correct responses were weak in both MA (24.1 +/- 7.0) and RJ
      (26.3 +/- 7.3). Bivariate analysis showed an association between viral hepatitis
      awareness and both education level (p < 0.001) and family income (p < 0.01).
      Desirable scores were more common in female participants (61%), those aged
      between 21-30 years (40%), those with a secondary education (51.7%), those who
      received high income (31.6%), and those from RJ (70.0%). Health education
      campaigns in these cities are recommended to increase knowledge and reduce the
      transmission of these viruses.

PMID- 29364167
TI  - Preventing Crystal Agglomeration of Pharmaceutical Crystals Using Temperature
      Cycling and a Novel Membrane Crystallization Procedure for Seed Crystal
      Generation.
AB  - In this work, a novel membrane crystallization system was used to crystallize
      micro-sized seeds of piroxicam monohydrate by reverse antisolvent addition.
      Membrane crystallization seeds were compared with seeds produced by conventional
      antisolvent addition and polymorphic transformation of a fine powdered sample of
      piroxicam form I in water. The membrane crystallization process allowed for a
      consistent production of pure monohydrate crystals with narrow size distribution
      and without significant agglomeration. The seeds were grown in 350 g of 20:80 w/w
      acetone-water mixture. Different seeding loads were tested and temperature
      cycling was applied in order to avoid agglomeration of the growing crystals
      during the process. Focused beam reflectance measurement (FBRM); and particle
      vision and measurement (PVM) were used to monitor crystal growth; nucleation and
      agglomeration during the seeded experiments. Furthermore; Raman spectroscopy was
      used to monitor solute concentration and estimate the overall yield of the
      process. Membrane crystallization was proved to be the most convenient and
      consistent method to produce seeds of highly agglomerating compounds; which can
      be grown via cooling crystallization and temperature cycling.

PMID- 29364168
TI  - Renal Tubule Repair: Is Wnt/beta-Catenin a Friend or Foe?
AB  - Wnt/beta-catenin signaling is extremely important for proper kidney development.
      This pathway is also upregulated in injured renal tubular epithelia, both in
      acute kidney injury and chronic kidney disease. The renal tubular epithelium is
      an important target of kidney injury, and its response (repair versus persistent
      injury) is critical for determining whether tubulointerstitial fibrosis, the
      hallmark of chronic kidney disease, develops. This review discusses how Wnt/beta
      catenin signaling in the injured tubular epithelia promotes either repair or
      fibrosis after kidney injury. There is data suggesting that epithelial Wnt/beta
      catenin signaling is beneficial in acute kidney injury and important in tubular
      progenitors responsible for epithelial repair. The role of Wnt/beta-catenin
      signaling in chronically injured epithelia is less clear. There is convincing
      data that Wnt/beta-catenin signaling in interstitial fibroblasts and pericytes
      contributes to the extracellular matrix accumulation that defines fibrosis.
      However, some recent studies question whether Wnt/beta-catenin signaling in
      chronically injured epithelia actually promotes fibrosis or repair.

PMID- 29364169
TI  - Proteomic Analysis of Differentially-Expressed Proteins in the Liver of
      Streptozotocin-Induced Diabetic Rats Treated with Parkia biglobosa Protein
      Isolate.
AB  - Protein isolate from Parkia biglobosa seeds is believed to possess excellent anti
      diabetic properties. The purpose of this study was to identify differentially
      expressed proteins in liver of streptozotocin-induced diabetic rats treated with
      Parkia biglobosa seeds protein isolate (PBPi). In this study, total proteins
      extracted from rat liver were separated on one-dimensional SDS polyacrylamide gel
      (1D SDS-PAGE) and stained with Coomassie brilliant blue (CBB) to visualize
      protein bands. We observed that protein bands in the region of 10-15 kDa were
      altered by the different treatments; these bands were selected and excised for in
      gel digestion and peptide extraction followed by nLC-MS, MALDI-TOF MS, and LIFT
      MS/MS. A database search with the Mascot algorithm positively identified four
      differentially expressed proteins. These proteins are known to be responsible for
      diverse biological functions within various organs and tissues. The present
      result gives insight and understanding into possible molecular mechanisms by
      which streptozotocin causes various alterations in proteins found in the liver of
      diabetic rats and the possible modulatory role of PBPi in the management of
      streptozotocin-induced diabetes.

PMID- 29364170
TI  - Erinacine A-Enriched Hericium erinaceus Mycelium Produces Antidepressant-Like
      Effects through Modulating BDNF/PI3K/Akt/GSK-3beta Signaling in Mice.
AB  - Antidepressant-like effects of ethanolic extract of Hericium erinaceus (HE)
      mycelium enriched in erinacine A on depressive mice challenged by repeated
      restraint stress (RS) were examined. HE at 100, 200 or 400 mg/kg body weight/day
      was orally given to mice for four weeks. After two weeks of HE administration,
      all mice except the control group went through with 14 days of RS protocol.
      Stressed mice exhibited various behavioral alterations, such as extending
      immobility time in the tail suspension test (TST) and forced swimming test (FST),
      and increasing the number of entries in open arm (POAE) and the time spent in the
      open arm (PTOA). Moreover, the levels of norepinephrine (NE), dopamine (DA) and
      serotonin (5-HT) were decreased in the stressed mice, while the levels of
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha were increased. These
      changes were significantly inverted by the administration of HE, especially at
      the dose of 200 or 400 mg/kg body weight/day. Additionally, HE was shown to
      activate the BDNF/TrkB/PI3K/Akt/GSK-3beta pathways and block the NF-kappaB
      signals in mice. Taken together, erinacine A-enriched HE mycelium could reverse
      the depressive-like behavior caused by RS and was accompanied by the modulation
      of monoamine neurotransmitters as well as pro-inflammatory cytokines, and
      regulation of BDNF pathways. Therefore, erinacine A-enriched HE mycelium could be
      an attractive agent for the treatment of depressive disorders.

PMID- 29364172
TI  - Service Migration from Cloud to Multi-tier Fog Nodes for Multimedia Dissemination
      with QoE Support.
AB  - A wide range of multimedia services is expected to be offered for mobile users
      via various wireless access networks. Even the integration of Cloud Computing in
      such networks does not support an adequate Quality of Experience (QoE) in areas
      with high demands for multimedia contents. Fog computing has been conceptualized
      to facilitate the deployment of new services that cloud computing cannot provide,
      particularly those demanding QoE guarantees. These services are provided using
      fog nodes located at the network edge, which is capable of virtualizing their
      functions/applications. Service migration from the cloud to fog nodes can be
      actuated by request patterns and the timing issues. To the best of our knowledge,
      existing works on fog computing focus on architecture and fog node deployment
      issues. In this article, we describe the operational impacts and benefits
      associated with service migration from the cloud to multi-tier fog computing for
      video distribution with QoE support. Besides that, we perform the evaluation of
      such service migration of video services. Finally, we present potential research
      challenges and trends.

PMID- 29364171
TI  - What Works? Toward a New Classification System for Mental Health Supported
      Accommodation Services: The Simple Taxonomy for Supported Accommodation (STAX
      SA).
AB  - Inconsistent terminology and variation in service models have made synthesis of
      the supported accommodation literature challenging. To overcome this, we
      developed a brief, categorical taxonomy that aimed to capture the defining
      features of different supported accommodation models: the simple taxonomy for
      supported accommodation (STAX-SA). Data from a previous review of existing
      classification systems were used to develop the taxonomy structure. After initial
      testing and amendments, the STAX-SA and an existing taxonomy were applied to 132
      supported accommodation service descriptions drawn from two systematic reviews
      and their performance compared. To assess external validity, the STAX-SA was
      distributed to a sample of supported accommodation managers in England and they
      were asked to use it to classify their services. The final version of the STAX-SA
      comprised of five supported accommodation 'types', based on four domains;
      Staffing location; Level of support; Emphasis on move-on; and Physical setting.
      The STAX-SA accurately categorized 71.1% (n = 94) of service descriptions,
      outperforming the comparison tool, and was not affected by publication date or
      research design. The STAX-SA effectively discriminated between 'real world'
      service models in England and 53.2% (n = 17) of service managers indicated that
      the taxonomy was 'Very effective' or 'Extremely effective' in capturing key
      characteristics of their service. The STAX-SA is an effective tool for
      classifying supported accommodation models and represents a promising approach to
      synthesizing the extant effectiveness literature. The authors recommend the
      development of reporting guidelines for future supported accommodation
      publications to facilitate comparison between models.

PMID- 29364173
TI  - Evaluation of the Validity and Reliability of the Chinese Healthy Eating Index.
AB  - The Chinese Healthy Eating Index (CHEI) is a measuring instrument of diet quality
      in accordance with the Dietary Guidelines for Chinese (DGC)-2016. The objective
      of the study was to evaluate the validity and reliability of the CHEI. Data from
      12,473 adults from the China Health and Nutrition Survey (CHNS)-2011, including 3
      day-24-h dietary recalls were used in this study. The CHEI was assessed by four
      exemplary menus developed by the DGC-2016, the general linear models, the
      independent t-test and the Mann-Whitney U-test, the Spearman's correlation
      analysis, the principal components analysis (PCA), the Cronbach's coefficient,
      and the Pearson correlation with nutrient intakes. A higher CHEI score was linked
      with lower exposure to known risk factors of Chinese diets. The CHEI scored
      nearly perfect for exemplary menus for adult men (99.8), adult women (99.7), and
      the healthy elderly (99.1), but not for young children (91.2). The CHEI was able
      to distinguish the difference in diet quality between smokers and non-smokers (P
      < 0.0001), people with higher and lower education levels (P < 0.0001), and people
      living in urban and rural areas (P < 0.0001). Low correlations with energy intake
      for the CHEI total and component scores (|r| < 0.34, P < 0.01) supported the
      index assessed diet quality independently of diet quantity. The PCA indicated
      that underlying multiple dimensions compose the CHEI, and Cronbach's coefficient
      alpha was 0.22. Components of dairy, fruits and cooking oils had the greatest
      impact on the total score. People with a higher CHEI score had not only a higher
      absolute intake of nutrients (P < 0.001), but also a more nutrient-dense diet (P
      < 0.001). Our findings support the validity and reliability of the CHEI when
      using the 3-day-24-h recalls.

PMID- 29364174
TI  - Molecular Understanding of the Activation of CB1 and Blockade of TRPV1 Receptors:
      Implications for Novel Treatment Strategies in Osteoarthritis.
AB  - Osteoarthritis (OA) is a joint disease in which cartilage degenerates as a result
      of mechanical and biochemical changes. The main OA symptom is chronic pain
      involving both peripheral and central mechanisms of nociceptive processing. Our
      previous studies have implicated the benefits of dual- over single-acting
      compounds interacting with the endocannabinoid system (ECS) in OA treatment. In
      the present study, we focused on the specific molecular alterations associated
      with pharmacological treatment. OA was induced in Wistar rats by intra-articular
      injection of 3 mg of monoiodoacetate (MIA). Single target compounds (URB597, an
      FAAH inhibitor, and SB366791, a TRPV1 antagonist) and a dual-acting compound
      OMDM198 (FAAH inhibitor/TRPV1 antagonist) were used in the present study. At day
      21 post-MIA injection, rats were sacrificed 1 h after i.p. treatment, and changes
      in mRNA expression were evaluated in the lumbar spinal cord by RT-qPCR. Following
      MIA administration, we observed 2-4-fold increase in mRNA expression of targeted
      receptors (Cnr1, Cnr2, and Trpv1), endocannabinoid degradation enzymes (Faah,
      Ptgs2, and Alox12), and TRPV1 sensitizing kinases (Mapk3, Mapk14, Prkcg, and
      Prkaca). OMDM198 treatment reversed some of the MIA effects on the spinal cord
      towards intact levels (Alox12, Mapk14, and Prkcg). Apparent regulation of ECS and
      TRPV1 in response to pharmacological intervention is a strong justification for
      novel ECS-based multi-target drug treatment in OA.

PMID- 29364175
TI  - Tactile-Sensing Based on Flexible PVDF Nanofibers via Electrospinning: A Review.
AB  - The flexible tactile sensor has attracted widespread attention because of its
      great flexibility, high sensitivity, and large workable range. It can be
      integrated into clothing, electronic skin, or mounted on to human skin. Various
      nanostructured materials and nanocomposites with high flexibility and electrical
      performance have been widely utilized as functional materials in flexible tactile
      sensors. Polymer nanomaterials, representing the most promising materials,
      especially polyvinylidene fluoride (PVDF), PVDF co-polymer and their
      nanocomposites with ultra-sensitivity, high deformability, outstanding chemical
      resistance, high thermal stability and low permittivity, can meet the flexibility
      requirements for dynamic tactile sensing in wearable electronics. Electrospinning
      has been recognized as an excellent straightforward and versatile technique for
      preparing nanofiber materials. This review will present a brief overview of the
      recent advances in PVDF nanofibers by electrospinning for flexible tactile sensor
      applications. PVDF, PVDF co-polymers and their nanocomposites have been
      successfully formed as ultrafine nanofibers, even as randomly oriented PVDF
      nanofibers by electrospinning. These nanofibers used as the functional layers in
      flexible tactile sensors have been reviewed briefly in this paper. The beta-phase
      content, which is the strongest polar moment contributing to piezoelectric
      properties among all the crystalline phases of PVDF, can be improved by adjusting
      the technical parameters in electrospun PVDF process. The piezoelectric
      properties and the sensibility for the pressure sensor are improved greatly when
      the PVDF fibers become more oriented. The tactile performance of PVDF composite
      nanofibers can be further promoted by doping with nanofillers and nanoclay.
      Electrospun P(VDF-TrFE) nanofiber mats used for the 3D pressure sensor achieved
      excellent sensitivity, even at 0.1 Pa. The most significant enhancement is that
      the aligned electrospun core-shell P(VDF-TrFE) nanofibers exhibited almost 40
      times higher sensitivity than that of pressure sensor based on thin-film PVDF.

PMID- 29364176
TI  - Secular Trends in Energy and Macronutrient Intakes and Distribution among Adult
      Females (1991-2015): Results from the China Health and Nutrition Survey.
AB  - With rapid nutrition transition in China, dietary intake and nutritional status
      of women has gained more and more attention in the past decades. This study aimed
      to investigate temporal trends of total energy and macronutrient intakes among
      Chinese adult females. The longitudinal data are from the Chinese Health and
      Nutrition Survey (CHNS, 1991-2015). Information on the intake of energy and
      macronutrient was obtained from consecutive three-day dietary recall techniques
      and compared with the Chinese Dietary Reference Intakes (DRI). Mixed-effect
      models were performed to evaluate temporal trends of total energy and
      macronutrient intake. From 1991 to 2015, a significant reduction in daily energy,
      protein and carbohydrate intakes was seen among all adult females (p < 0.001).
      Daily fat intake, the proportion of energy from fat, the proportion of females
      consuming more than 30% of energy from fat and less than 50% of energy from
      carbohydrate were observed significant increment in the present study (p <
      0.001). In 2015, the proportion met the DRI for energy and protein intakes were
      47.0% and 48.0%, respectively; the proportion with lower carbohydrate and higher
      fat intakes compare with the DRI were 45.5% and 66.9%, respectively. Further
      nutritional education and policy interventions still needed to improve nutrition
      status for Chinese females.

PMID- 29364177
TI  - Allostatic Load and Effort-Reward Imbalance: Associations over the Working
      Career.
AB  - Although associations between work stressors and stress-related biomarkers have
      been reported in cross-sectional studies, the use of single time measurements of
      work stressors could be one of the reasons for inconsistent associations. This
      study examines whether repeated reports of work stress towards the end of the
      working career predicts allostatic load, a measure of chronic stress related
      physiological processes. Data from waves 2 to 6 of the English Longitudinal Study
      of Ageing (ELSA) were analysed, with a main analytical sample of 2663 older
      adults (aged 50+) who had at least one measurement of effort-reward imbalance
      between waves 2-6 and a measurement of allostatic load at wave 6. Cumulative work
      stress over waves 2-6 were measured by the effort-reward imbalance model. ELSA
      respondents who had reported two or more occasions of imbalance had a higher
      (0.3) estimate of the allostatic load index than those who did not report any
      imbalance, controlling for a range of health and socio-demographic factors, as
      well as allostatic load at baseline. More recent reports of imbalance were
      significantly associated with a higher allostatic load index, whereas reports of
      imbalance from earlier waves of ELSA were not. The accumulation of work related
      stressors could have adverse effects on chronic stress biological processes.

PMID- 29364178
TI  - Disrupting the Btk Pathway Suppresses COPD-Like Lung Alterations in
      Atherosclerosis Prone ApoE-/- Mice Following Regular Exposure to Cigarette Smoke.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with severe chronic
      inflammation that promotes irreversible tissue destruction. Moreover, the most
      broadly accepted cause of COPD is exposure to cigarette smoke. There is no
      effective cure and significantly, the mechanism behind the development and
      progression of this disease remains unknown. Our laboratory has demonstrated that
      Bruton's tyrosine kinase (Btk) is a critical regulator of pro-inflammatory
      processes in the lungs and that Btk controls expression of matrix
      metalloproteinase-9 (MMP-9) in the alveolar compartment. For this study
      apolipoprotein E null (ApoE-/-) mice were exposed to SHS to facilitate study in a
      COPD/atherosclerosis comorbidity model. We applied two types of treatments,
      animals received either a pharmacological inhibitor of Btk or MMP-9 specific
      siRNA to minimize MMP-9 expression in endothelial cells or neutrophils. We have
      shown that these treatments had a protective effect in the lung. We have noted a
      decrease in alveolar changes related to SHS induced inflammation in treated
      animals. In summary, we are presenting a novel concept in the field of COPD,
      i.e., that Btk may be a new drug target for this disease. Moreover, cell specific
      targeting of MMP-9 may also benefit patients affected by this disease.

PMID- 29364179
TI  - Lycopene Attenuates Tulathromycin and Diclofenac Sodium-Induced Cardiotoxicity in
      Mice.
AB  - Recent experiments showed a potential cardiotoxic effect of the macrolide
      antibiotic (tulathromycin). This study was performed to investigate whether
      diclofenac sodium (DFS) potentiates the cardiotoxicity of tulathromycin and
      increases the cardioprotective effects of lycopene against DFS and tulathromycin.
      Seven groups (eight per group) of adult Swiss albino mice received saline
      (control), tulathromycin (a single subcutaneous dose of 28 mg/kg/bw on day 14),
      DFS (a single oral dose of 100 mg/kg/bw on day 14), tulathromycin plus DFS, or
      lycopene (oral, 10 mg/kg/bw daily for 15 d) combined with tulathromycin, DFS, or
      both. Compared to the control group, the administration of tulathromycin or DFS
      (individually or in combination) caused significantly elevated (p < 0.05) serum
      levels of Creatine kinase-myocardial B fraction (CK-MB), lactate dehydrogenase,
      and cardiac-specific troponin-T and tissue levels of nitric oxide and
      malondialdehyde that were accompanied by significantly decreased tissue reduced
      glutathione content and glutathione peroxidase, superoxide dismutase, and
      catalase antioxidant enzyme activity. Upon histopathological and
      immunohistochemical examination, the mean pathology scores and the percentages of
      caspase-3-, Bax-, and CK-positive regions were significantly higher in the
      tulathromycin- and/or DFS-treated groups than in control mice. For all these
      parameters, the pathological changes were more significant in the tulathromycin
      DFS combination group than in mice treated with either drug individually.
      Interestingly, co-administration of lycopene with tulathromycin and/or DFS
      significantly ameliorated the changes described above. In conclusion, DFS could
      potentiate the cardiotoxic effects of tulathromycin, whereas lycopene can serve
      as a cardioprotective agent against DFS and tulathromycin.

PMID- 29364181
TI  - Non-Clinical Contribution to Clinical Trials during Lead Optimization Phase.
AB  - This manuscript comments on guidelines related to requirements for clinical
      trials for new drugs and the importance of considering regulatory criteria in the
      planning phase, in order to enhance the utility of data generated in basic
      research. Suggestions are made for optimizing regulatory management to improve
      the likelihood of acceptance of pre-clinical data prior to Clinical Phase I
      trials (early clinical trials).

PMID- 29364180
TI  - Late-Onset N-Acetylglutamate Synthase Deficiency: Report of a Paradigmatic Adult
      Case Presenting with Headaches and Review of the Literature.
AB  - N-acetylglutamate synthase deficiency (NAGSD) is an extremely rare urea cycle
      disorder (UCD) with few adult cases so far described. Diagnosis of late-onset
      presentations is difficult and delayed treatment may increase the risk of severe
      hyperammonemia. We describe a 52-year-old woman with recurrent headaches who
      experienced an acute onset of NAGSD. As very few papers focus on headaches in
      UCDs, we also report a literature review of types and pathophysiologic mechanisms
      of UCD-related headaches. In our case, headaches had been present since puberty
      (3-4 days a week) and were often accompanied by nausea, vomiting, or behavioural
      changes. Despite three previous episodes of altered consciousness, ammonia was
      measured for the first time at 52 years and levels were increased. Identification
      of the new homozygous c.344C>T (p.Ala115Val) NAGS variant allowed the definite
      diagnosis of NAGSD. Bioinformatic analysis suggested that an order/disorder
      alteration of the mutated form could affect the arginine-binding site, resulting
      in poor enzyme activation and late-onset presentation. After optimized treatment
      for NAGSD, ammonia and amino acid levels were constantly normal and prevented
      other headache bouts. The manuscript underlies that headache may be the
      presenting symptom of UCDs and provides clues for the rapid diagnosis and
      treatment of late-onset NAGSD.

PMID- 29364182
TI  - Investigating Colorimetric Protein Array Assay Schemes for Detection of
      Recurrence of Bladder Cancer.
AB  - A colorimetric microarray for the multiplexed detection of recurrence of bladder
      cancer including protein markers interleukin-8 (IL8), decorin (DCN), and vascular
      endothelial growth factor (VEGF) was established to enable easy and cheap read
      out by a simple office scanner paving the way for quick therapy monitoring at
      doctors' offices. The chip is based on the principle of a sandwich immunoassay
      and was optimized prior to multiplexing using IL8 as a model marker. Six
      different colorimetric assay formats were evaluated using a detection antibody
      (dAB) labeled with (I) gold (Au) nanoparticles (NPs), (II) carbon NPs, (III)
      oxidized carbon NPs, and a biotinylated dAB in combination with (IV) neutravidin
      carbon, (V) streptavidin (strp)-gold, and (VI) strp-horseradish peroxidase (HRP).
      Assay Format (III) worked best for NP-based detection and showed a low background
      while the enzymatic approach, using 3,3',5,5'-tetramethylbenzidine (TMB)
      substrate, led to the most intense signals with good reproducibility. Both assay
      formats showed consistent spot morphology as well as detection limits lower than
      15 ng/L IL8 and were thus applied for the multiplexed detection of IL8, DCN, and
      VEGF in synthetic urine. Colorimetric detection in urine (1:3) yields reaction
      signals and measurement ranges well comparable with detection in the assay
      buffer, as well as excellent data reproducibility as indicated by the coefficient
      of variation (CV 5-9%).

PMID- 29364183
TI  - Antioxidant and Cytoprotective Effects of Tibetan Tea and Its Phenolic
      Components.
AB  - Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this
      study, a lyophilized aqueous extract of Tibetan tea (LATT) was prepared and
      analyzed by HPLC. The results suggested that there were at least five phenolic
      components, including gallic acid, and four catechins (i.e., (+)-catechin, (-)
      catechin gallate (CG), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin
      gallate). Gallic acid, the four catechins, and LATT were then comparatively
      investigated by four antioxidant assays: ferric reducing antioxidant power, 2
      phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO*) scavenging,
      1,1-diphenyl-2-picryl-hydrazl radical scavenging, and 2,2'-azino-bis(3-ethylbenzo
      thiazoline-6-sulfonic acid) radical scavenging assays. In these assays, LATT,
      along with the five phenolic components, increased their antioxidant effects in a
      concentration-dependent manner; however, the half maximal scavenging
      concentrations of ECG were always lower than those of CG. Gallic acid and the
      four catechins were also suggested to chelate Fe2+ based on UV-visible spectral
      analysis. Ultra-performance liquid chromatography coupled with electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF
      MS/MS) analysis suggested that, when mixed with PTIO*, the five phenolic
      components could yield two types of radical adduct formation (RAF) products
      (i.e., tea phenolic dimers and tea phenolic-PTIO* adducts). In a flow cytometry
      assay, (+)-catechin and LATT was observed to have a cytoprotective effect towards
      oxidative-stressed bone marrow-derived mesenchymal stem cells. Based on this
      evidence, we concluded that LATT possesses antioxidative or cytoprotective
      properties. These effects may mainly be attributed to the presence of phenolic
      components, including gallic acid and the four catechins. These phenolic
      components may undergo electron transfer, H+-transfer, and Fe2+-chelating
      pathways to exhibit antioxidative or cytoprotective effects. In these effects,
      two diastereoisomeric CG and ECG showed differences to which a steric effect from
      the 2-carbon may contribute. Phenolic component decay may cause RAF in the
      antioxidant process.

PMID- 29364185
TI  - Secure Transmission of Cooperative Zero-Forcing Jamming for Two-User SWIPT Sensor
      Networks.
AB  - In this paper, the secrecy performance of the two-user simultaneous wireless
      information and power transfer (SWIPT) sensor networks is studied and a novel
      secure transmission scheme of cooperative zero-forcing (ZF) jamming is proposed.
      The two sensors opportunistically conduct the SWIPT and cooperative ZF jamming,
      respectively, where the energy required for jamming the eavesdropper is provided
      by the SWIPT operation so as to keep the energy balance at the sensors in the
      long run. By deriving the exact closed-form expressions of the secrecy outage
      probability and the secrecy throughout, we provide an effective approach to
      precisely assess the impacts of key parameters on the secrecy performance of the
      system. It has been shown that the secrecy outage probability is a monotonically
      increasing function of the growth of secrecy rate ( R s ), and a monotonically
      decreasing function of the increase of the transmit signal-to-noise ratio ( gamma
      S ), and energy conversion efficiency ( eta ). Furthermore, the secrecy
      throughput could be enhanced when eta increases, which becomes especially obvious
      when a large gamma S is provided. Moreover, the existence of an optimum R s
      maximizing the secrecy throughput is depicted, which also grows with the increase
      of gamma S . Simulations are provided for the validation of the analysis.

PMID- 29364184
TI  - Oral Contact Events and Caregiver Hand Hygiene: Implications for Fecal-Oral
      Exposure to Enteric Pathogens among Infants 3-9 Months Living in Informal, Peri
      Urban Communities in Kisumu, Kenya.
AB  - Childhood diarrhea is one of the leading causes of morbidity and mortality in
      children under five in low and middle-income countries, second only to
      respiratory illness. The mouthing behavior that is common in children exposes
      them to fecal-orally transmitted pathogens that can result in diarrhea; however,
      there is a need for further evidence on specific exposure routes. This study
      describes the frequency and diversity of two important routes of enteric pathogen
      exposure among infants 3-9 months of age: infant oral contact behavior and
      caregiver handwashing behavior. Data were collected through structured
      observations of 25 index infants for the oral contact data and 25 households for
      the caregiver handwashing data in a peri-urban setting in Kisumu (Obunga), Kenya.
      Breast was the most common type of oral contact event with an average of 3.00 per
      observation period and 0.5 events per hour. This was followed by a range of
      physical objects with an average of 2.49 per observation and 0.4 events per hour.
      The "infant's own hands" was the third most common oral contact, with an average
      of 2.16 events per hour, and 0.4 oral contact events per hour. Food and liquids
      were the 4th and 5th most common oral contact events with an average of 1.64 food
      contacts and 0.52 liquid oral contact events per observation period. Feeding
      events, including breastfeeding, were the most commonly observed key juncture-71%
      of total junctures observed were caregivers feeding children. This was followed
      by child cleaning (23%), caregiver toilet uses at (4%), and lastly food
      preparation at 2%. HWWS was observed only once before a feeding event (1%), twice
      after cleaning a child (9%), and twice after caregiver toilet use (40%). The
      combined implication of data from observing oral contact behavior in children and
      hand hygiene of caregivers suggests that caregiver hand hygiene prior to feeding
      events and after cleaning a child are priority interventions.

PMID- 29364186
TI  - Genetic Selection to Enhance Animal Welfare Using Meat Inspection Data from
      Slaughter Plants.
AB  - Animal health and welfare are monitored during meat inspection in many slaughter
      plants around the world. Carcasses are examined by meat inspectors and remarks
      are made with respect to different diseases, injuries, and other abnormalities.
      This is a valuable data resource for disease prevention and enhancing animal
      welfare, but it is rarely used for this purpose. Records on carcass remarks on
      140,375 finisher pigs were analyzed to investigate the possibility of genetic
      selection to reduce the risk of the most prevalent diseases and indicators of
      suboptimal animal welfare. As part of this, effects of some non-genetic factors
      such as differences between farms, sexes, and growth rates were also examined.
      The most frequent remarks were pneumonia (15.4%), joint disorders (9.8%),
      pleuritis (4.7%), pericarditis (2.3%), and liver lesions (2.2%). Joint disorders
      were more frequent in boars than in gilts. There were also significant
      differences between farms. Pedigree records were available for 142,324 pigs from
      14 farms and were used for genetic analysis. Heritability estimates for
      pneumonia, pleuritis, pericarditis, liver lesions, and joint disorders were 0.10,
      0.09, 0.14, 0.24, and 0.17 on the liability scale, respectively, suggesting the
      existence of substantial genetic variation. This was further confirmed though
      genome wide associations using deregressed breeding values as phenotypes. The
      genetic correlations between these remarks and finishing traits were small but
      mostly negative, suggesting the possibility of enhancing pig health and welfare
      simultaneously with genetic improvement in finishing traits. A selection index
      based on the breeding values for these traits and their economic values was
      developed. This index is used to enhance animal welfare in pig farms.

PMID- 29364188
TI  - Passive Infrared (PIR)-Based Indoor Position Tracking for Smart Homes Using
      Accessibility Maps and A-Star Algorithm.
AB  - Indoor occupants' positions are significant for smart home service systems, which
      usually consist of robot service(s), appliance control and other intelligent
      applications. In this paper, an innovative localization method is proposed for
      tracking humans' position in indoor environments based on passive infrared (PIR)
      sensors using an accessibility map and an A-star algorithm, aiming at providing
      intelligent services. First the accessibility map reflecting the visiting habits
      of the occupants is established through the integral training with indoor
      environments and other prior knowledge. Then the PIR sensors, which placement
      depends on the training results in the accessibility map, get the rough location
      information. For more precise positioning, the A-start algorithm is used to
      refine the localization, fused with the accessibility map and the PIR sensor
      data. Experiments were conducted in a mock apartment testbed. The ground truth
      data was obtained from an Opti-track system. The results demonstrate that the
      proposed method is able to track persons in a smart home environment and provide
      a solution for home robot localization.

PMID- 29364187
TI  - Deciphering the Functional Composition of Fusogenic Liposomes.
AB  - Cationic liposomes are frequently used as carrier particles for nucleic acid
      delivery. The most popular formulation is the equimolar mixture of two
      components, a cationic lipid and a neutral phosphoethanolamine. Its uptake
      pathway has been described as endocytosis. The presence of an aromatic molecule
      as a third component strongly influences the cellular uptake process and results
      in complete membrane fusion instead of endocytosis. Here, we systematically
      varied all three components of this lipid mixture and determined how efficiently
      the resulting particles fused with the plasma membrane of living mammalian cells.
      Our results show that an aromatic molecule and a cationic lipid component with
      conical molecular shape are essential for efficient fusion induction. While a
      neutral lipid is not mandatory, it can be used to control fusion efficiency and,
      in the most extreme case, to revert the uptake mechanism back to endocytosis.

PMID- 29364189
TI  - Polyphenolic Compounds Analysis of Old and New Apple Cultivars and Contribution
      of Polyphenolic Profile to the In Vitro Antioxidant Capacity.
AB  - Polyphenols are antioxidant ingredients in apples and are related to human health
      because of their free radical scavenging activities. The polyphenolic profiles of
      old and new apple cultivars (n = 15) were analysed using high-performance liquid
      chromatography (HPLC) with diode array detection (DAD). The in vitro antioxidant
      capacity was determined by total phenolic content (TPC) assay, hydrophilic trolox
      equivalent antioxidant capacity (H-TEAC) assay and hydrophilic oxygen radical
      absorbance (H-ORAC) assay. Twenty polyphenolic compounds were identified in all
      investigated apples by HPLC analysis. Quercetin glycosides (203 +/- 108 mg/100 g)
      were the main polyphenols in the peel and phenolic acids (10 +/- 5 mg/100 g) in
      the flesh. The calculated relative contribution of single compounds indicated
      flavonols (peel) and vitamin C (flesh) as the major contributors to the
      antioxidant capacity, in all cultivars investigated. The polyphenolic content
      (HPLC data) of the flesh differed significantly between old (29 +/- 7 mg/100 g)
      and new (13 +/- 4 mg/100 g) cultivars, and the antioxidant capacity of old apple
      cultivars was up to 30% stronger compared to new ones.

PMID- 29364190
TI  - A Novel Event-Based Incipient Slip Detection Using Dynamic Active-Pixel Vision
      Sensor (DAVIS).
AB  - In this paper, a novel approach to detect incipient slip based on the contact
      area between a transparent silicone medium and different objects using a
      neuromorphic event-based vision sensor (DAVIS) is proposed. Event-based
      algorithms are developed to detect incipient slip, slip, stress distribution and
      object vibration. Thirty-seven experiments were performed on five objects with
      different sizes, shapes, materials and weights to compare precision and response
      time of the proposed approach. The proposed approach is validated by using a high
      speed constitutional camera (1000 FPS). The results indicate that the sensor can
      detect incipient slippage with an average of 44.1 ms latency in unstructured
      environment for various objects. It is worth mentioning that the experiments were
      conducted in an uncontrolled experimental environment, therefore adding high
      noise levels that affected results significantly. However, eleven of the
      experiments had a detection latency below 10 ms which shows the capability of
      this method. The results are very promising and show a high potential of the
      sensor being used for manipulation applications especially in dynamic
      environments.

PMID- 29364191
TI  - Jasmonate-Elicited Stress Induces Metabolic Change in the Leaves of Leucaena
      leucocephala.
AB  - The plant Leucaena leucocephala was exposed to four jasmonate elicitors, i.e.,
      jasmonic acid (JA), methyl jasmonic acid (MeJA), jasmonoyl-l-isoleucine (JA-Ile)
      and 6-ethyl indanoyl glycine conjugate (2-[(6-ethyl-1-oxo-indane-4-carbonyl)
      amino]-acetic acid methyl ester) (CGM). The treatment was to mimic the herbivores
      and wounding stresses. By using NMR spectroscopy along with chemometric analysis,
      including principal component analysis (PCA) and partial least squares
      discriminant analysis (PLS-DA), the changes of metabolites in the leaves of L.
      leucocephala were determined under the stress as induced by the four elicitors.
      The challenge of JA-Ile caused an accumulation of lactic acid (6), beta-glucose
      (10), alanine (12), threonine (13), steroids (18), 3,4-dihydroxypyridine (19) and
      an unidentified compound 20. The chemometric analysis of the PCA and PLS-DA
      models indicated that the alternation of metabolites triggered by JA, MeJA, and
      CGM treatments were very minimum. In contrast, the treatment by JA-Ile could
      induce the most significant metabolic changes in the leaves. Moreover, there was
      very minimal new metabolite being detected in responding to the jasmonate-induced
      stresses. The results showed some metabolite concentrations changed after
      application of the elicitors, which may be related to a high level of tolerance
      to stress conditions as well as the strong ecological suitability of L.
      leucocephala.

PMID- 29364192
TI  - "Girls Have More Challenges; They Need to Be Locked Up": A Qualitative Study of
      Gender Norms and the Sexuality of Young Adolescents in Uganda.
AB  - Unequal power and gender norms expose adolescent girls to higher risks of HIV,
      early marriages, pregnancies and coerced sex. In Uganda, almost half of the girls
      below the age of 18 are already married or pregnant, which poses a danger to the
      lives of young girls. This study explores the social construction of gender norms
      from early childhood, and how it influences adolescents' agency. Contrary to the
      mainstream theory of agency, which focuses on the ability to make informed
      choices, adolescents' agency appears constrained by context-specific obstacles.
      This study adopted qualitative research approaches involving 132 participants. Of
      these, 44 were in-depth interviews and 11 were focus group discussions, parcelled
      out into separate groups of adolescents (12-14 years), teachers, and parents (n =
      88), in Western Uganda. Data were analysed manually using open and axial codes,
      and conclusions were inductive. Results show that gender norms are established
      early in life, and have a very substantial impact on the agency of young
      adolescents. There were stereotypical gender norms depicting boys as sexually
      active and girls as restrained; girls' movements were restricted; their sexual
      agency constrained; and prevention of pregnancy was perceived as a girl's
      responsibility. Programs targeting behavioural change need to begin early in the
      lives of young children. They should target teachers and parents about the values
      of gender equality and strengthen the legal system to create an enabling
      environment to address the health and wellbeing of adolescents.

PMID- 29364193
TI  - Preparation and Characterization of Antimicrobial Films Based on LDPE/Ag
      Nanoparticles with Potential Uses in Food and Health Industries.
AB  - In this work, the antimicrobial effect of silver nanoparticles in polyethylene
      based nanocomposites has been investigated using a non-conventional processing
      method to produce homogeneous materials. High energy ball milling under cryogenic
      conditions was used to achieve a powder of well-blended low-density polyethylene
      and commercial silver nanoparticles. The final composites in the form of films
      were obtained by hot pressing. The effect of various silver nanoparticles content
      (0, 0.5, 1 and 2 wt %) on the properties of low-density polyethylene and the
      antimicrobial effectiveness of the composite against DH5alpha Escherichia coli
      were studied. The presence of silver nanoparticles did not seem to affect the
      surface energy and thermal properties of the materials. Apart from the inhibition
      of bacterial growth, slight changes in the aspect ratio of the bacteria with the
      content of particles were observed, suggesting a direct relationship between the
      presence of silver nanoparticles and the proliferation of DH5alpha E. coli
      (Escherichia coli) cells. Results indicate that these materials may be used to
      commercially produce antimicrobial polymers with potential applications in the
      food and health industries.

PMID- 29364194
TI  - Ship Detection in Gaofen-3 SAR Images Based on Sea Clutter Distribution Analysis
      and Deep Convolutional Neural Network.
AB  - Target detection is one of the important applications in the field of remote
      sensing. The Gaofen-3 (GF-3) Synthetic Aperture Radar (SAR) satellite launched by
      China is a powerful tool for maritime monitoring. This work aims at detecting
      ships in GF-3 SAR images using a new land masking strategy, the appropriate model
      for sea clutter and a neural network as the discrimination scheme. Firstly, the
      fully convolutional network (FCN) is applied to separate the sea from the land.
      Then, by analyzing the sea clutter distribution in GF-3 SAR images, we choose the
      probability distribution model of Constant False Alarm Rate (CFAR) detector from
      K-distribution, Gamma distribution and Rayleigh distribution based on a tradeoff
      between the sea clutter modeling accuracy and the computational complexity.
      Furthermore, in order to better implement CFAR detection, we also use truncated
      statistic (TS) as a preprocessing scheme and iterative censoring scheme (ICS) for
      boosting the performance of detector. Finally, we employ a neural network to re
      examine the results as the discrimination stage. Experiment results on three GF-3
      SAR images verify the effectiveness and efficiency of this approach.

PMID- 29364196
TI  - A two-dose hepatitis B vaccine for adults (Heplisav-B).

PMID- 29364197
TI  - Semaglutide (Ozempic)--another injectable GLP-1 receptor agonist for type 2
      diabetes.

PMID- 29364198
TI  - L-glutamine (Endari) for sickle cell disease.

PMID- 29364195
TI  - Regulation of Three Virulence Strategies of Mycobacterium tuberculosis: A Success
      Story.
AB  - Tuberculosis remains one of the deadliest diseases. Emergence of drug-resistant
      and multidrug-resistant M. tuberculosis strains makes treating tuberculosis
      increasingly challenging. In order to develop novel intervention strategies,
      detailed understanding of the molecular mechanisms behind the success of this
      pathogen is required. Here, we review recent literature to provide a systems
      level overview of the molecular and cellular components involved in divalent
      metal homeostasis and their role in regulating the three main virulence
      strategies of M. tuberculosis: immune modulation, dormancy and phagosomal
      rupture. We provide a visual and modular overview of these components and their
      regulation. Our analysis identified a single regulatory cascade for these three
      virulence strategies that respond to limited availability of divalent metals in
      the phagosome.

PMID- 29364199
TI  - Neratinib (Nerlynx) for HER2-positive breast cancer.

PMID- 29364200
TI  - In brief: Olmesartan and sprue-like enteropathy.

PMID- 29364201
TI  - A Rapid and Efficient Method to Dissect Pupal Wings of Drosophila Suitable for
      Immunodetections or PCR Assays.
AB  - Wing development in Drosophila melanogaster is an ideal model for studying
      morphogenesis at tissue level. These appendages develop from a group of cells
      named wing imaginal discs formed during embryonic development. In the larval
      stages the imaginal discs grow, increasing its number of cells and forming
      monolayered epithelial structures. Inside the pupal case, the imaginal discs bud
      out and fold into bilayers along a line that becomes the future margin of the
      wing. During this process, the longitudinal primodia veins originate vein cells
      on the prospective dorsal and ventral surfaces of the wing. During the pupal
      stage the stripes of vein cells of each surface communicate in order to generate
      tight tubes; at the same time, the cross-veins begin their formation. With the
      help of appropriate molecular markers, it is possible to identify the major
      elements composing the wing during its development. For this reason, the ability
      to accurately detect transcripts or proteins in this structure is critical for
      studying their abundance and localization related to the development process of
      the wing. The procedure described here focuses on manipulating pupal wings,
      providing detailed instructions on how to dissect the wing during the pupal
      stage. The dissection of pupal tissue is more difficult to perform than their
      counterparts in third instar larvae. This is why this approach was developed, to
      obtain rapid and efficient high quality samples. Details of how to immunostain
      and mount these wing samples, to allow the visualization of proteins or cell
      components, are provided in the protocol. With little expertise it is possible to
      collect 8-10 high quality pupal wings in a short amount of time.

PMID- 29364202
TI  - Ultrathin Porated Elastic Hydrogels As a Biomimetic Basement Membrane for Dual
      Cell Culture.
AB  - The basement membrane is a critical component of cellular bilayers that can vary
      in stiffness, composition, architecture, and porosity. In vitro studies of
      endothelial-epithelial bilayers have traditionally relied on permeable support
      models that enable bilayer culture, but permeable supports are limited in their
      ability to replicate the diversity of human basement membranes. In contrast,
      hydrogel models that require chemical synthesis are highly tunable and allow for
      modifications of both the material stiffness and the biochemical composition via
      incorporation of biomimetic peptides or proteins. However, traditional hydrogel
      models are limited in functionality because they lack pores for cell-cell
      contacts and functional in vitro migration studies. Additionally, due to the
      thickness of traditional hydrogels, incorporation of pores that span the entire
      thickness of hydrogels has been challenging. In the present study, we use poly
      (ethylene-glycol) (PEG) hydrogels and a novel zinc oxide templating method to
      address the previous shortcomings of biomimetic hydrogels. As a result, we
      present an ultrathin, basement membrane-like hydrogel that permits the culture of
      confluent cellular bilayers on a customizable scaffold with variable pore
      architectures, mechanical properties, and biochemical composition.

PMID- 29364203
TI  - Plant Promoter Analysis: Identification and Characterization of Root Nodule
      Specific Promoter in the Common Bean.
AB  - The upstream sequences of gene coding sequences are termed as promoter sequences.
      Studying the expression patterns of promoters are very significant in
      understanding the gene regulation and spatiotemporal expression patterns of
      target genes. On the other hand, it is also critical to establish promoter
      evaluation tools and genetic transformation techniques that are fast, efficient,
      and reproducible. In this study, we investigated the spatiotemporal expression
      pattern of the rhizobial symbiosis-specific nodule inception (NIN) promoter of
      Phaseolus vulgaris in the transgenic hairy roots. Using plant genome databases
      and analysis tools we identified, isolated, and cloned the P. vulgaris NIN
      promoter in a transcriptional fusion to the chimeric reporter beta-glucuronidase
      (GUS) GUS-enhanced::GFP. Further, this protocol describes a rapid and versatile
      system of genetic transformation in the P. vulgaris using Agrobacterium
      rhizogenes induced hairy roots. This system generates >=2 cm hairy roots at 10 to
      12 days after transformation. Next, we assessed the spatiotemporal expression of
      NIN promoter in Rhizobium inoculated hairy roots at periodic intervals of post
      inoculation. Our results depicted by GUS activity show that the NIN promoter was
      active during the process of nodulation. Together, the present protocol
      demonstrates how to identify, isolate, clone, and characterize a plant promoter
      in the common bean hairy roots. Moreover, this protocol is easy to use in non
      specialized laboratories.

PMID- 29364204
TI  - Melt Electrospinning Writing of Three-dimensional Poly(epsilon-caprolactone)
      Scaffolds with Controllable Morphologies for Tissue Engineering Applications.
AB  - This tutorial reflects on the fundamental principles and guidelines for
      electrospinning writing with polymer melts, an additive manufacturing technology
      with great potential for biomedical applications. The technique facilitates the
      direct deposition of biocompatible polymer fibers to fabricate well-ordered
      scaffolds in the sub-micron to micro scale range. The establishment of a stable,
      viscoelastic, polymer jet between a spinneret and a collector is achieved using
      an applied voltage and can be direct-written. A significant benefit of a typical
      porous scaffold is a high surface-to-volume ratio which provides increased
      effective adhesion sites for cell attachment and growth. Controlling the printing
      process by fine-tuning the system parameters enables high reproducibility in the
      quality of the printed scaffolds. It also provides a flexible manufacturing
      platform for users to tailor the morphological structures of the scaffolds to
      their specific requirements. For this purpose, we present a protocol to obtain
      different fiber diameters using melt electrospinning writing (MEW) with a guided
      amendment of the parameters, including flow rate, voltage and collection speed.
      Furthermore, we demonstrate how to optimize the jet, discuss often experienced
      technical challenges, explain troubleshooting techniques and showcase a wide
      range of printable scaffold architectures.

PMID- 29364205
TI  - Live-cell Imaging of Fungal Cells to Investigate Modes of Entry and Subcellular
      Localization of Antifungal Plant Defensins.
AB  - Small cysteine-rich defensins are one of the largest groups of host defense
      peptides present in all plants. Many plant defensins exhibit potent in vitro
      antifungal activity against a broad-spectrum of fungal pathogens and therefore
      have the potential to be used as antifungal agents in transgenic crops. In order
      to harness the full potential of plant defensins for diseases control, it is
      crucial to elucidate their mechanisms of action (MOA). With the advent of
      advanced microscopy techniques, live-cell imaging has become a powerful tool for
      understanding the dynamics of the antifungal MOA of plant defensins. Here, a
      confocal microscopy based live-cell imaging method is described using two
      fluorescently labeled plant defensins (MtDef4 and MtDef5) in combination with
      vital fluorescent dyes. This technique enables real-time visualization and
      analysis of the dynamic events of MtDef4 and MtDef5 internalization into fungal
      cells. Importantly, this assay generates a wealth of information including
      internalization kinetics, mode of entry and subcellular localization of these
      peptides. Along with other cell biological tools, these methods have provided
      critical insights into the dynamics and complexity of the MOA of these peptides.
      These tools can also be used to compare the MOA of these peptides against
      different fungi.

PMID- 29364206
TI  - In Vitro Phagocytosis of Myelin Debris by Bone Marrow-Derived Macrophages.
AB  - Bone marrow-derived macrophages (BMDMs) are mature leukocytes that serve a
      critical physiological role as professional phagocytes capable of clearing a
      variety of particles. Normally, BMDMs are restricted from the central nervous
      system (CNS), but following an injury, they can readily infiltrate. Once within
      the injured CNS tissue, BMDMs are the primary cell type responsible for the
      clearance of injury-derived cellular debris, including large quantities of lipid
      rich myelin debris. The neuropathological ramifications of BMDM infiltration and
      myelin debris phagocytosis within the CNS are complex and not well understood.
      The protocols described here, allow for the direct in vitro study of BMDMs in the
      context of CNS injury. We cover murine BMDM isolation and culture, myelin debris
      preparation, and assays to assess BMDM myelin debris phagocytosis. These
      techniques produce robust quantifiable results without the need for significant
      specialized equipment or materials, yet can be easily customized to meet the
      needs of researchers.

PMID- 29364207
TI  - Protocol for HER2 FISH Using a Non-cross-linking, Formalin-free Tissue Fixative
      to Combine Advantages of Cryo-preservation and Formalin Fixation.
AB  - Morphologic assessment of formalin-fixed, paraffin-embedded (FFPE) tissue samples
      has been the gold standard for cancer diagnostics for decades due to its
      excellent preservation of morphology. Personalized medicine increasingly provides
      individually adapted and targeted therapies for characterized individual diseases
      enabled by combined morphological and molecular analytical technologies and
      diagnostics. Performance of morphologic and molecular assays from the same FFPE
      specimen is challenging because of the negative impact of formalin due to
      chemical modification and cross-linking of nucleic acids and proteins. A non
      cross-linking, formalin-free tissue fixative has been recently developed to
      fulfil both requirements, i.e., to preserve morphology like FFPE and biomolecules
      like cryo-preservation. Since FISH is often required in combination with
      histopathology and molecular diagnostics, we tested the applicability of FISH
      protocols on tissues treated with this new fixative. We found that formalin post
      fixation of histological sections of non-cross-linking, formalin-free and
      paraffin-embedded (NCFPE) breast cancer tissue generated equivalent results to
      those with FFPE tissue in human epidermal growth factor receptor 2 (HER2) FISH
      analysis. This protocol describes how a FISH assay originally developed and
      validated for FFPE tissue can be used for NCFPE tissues by a simple post-fixation
      step of histological sections.

PMID- 29364208
TI  - Modified Roller Tube Method for Precisely Localized and Repetitive Intermittent
      Imaging During Long-term Culture of Brain Slices in an Enclosed System.
AB  - Cultured rodent brain slices are useful for studying the cellular and molecular
      behavior of neurons and glia in an environment that maintains many of their
      normal in vivo interactions. Slices obtained from a variety of transgenic mouse
      lines or use of viral vectors for expression of fluorescently tagged proteins or
      reporters in wild type brain slices allow for high-resolution imaging by
      fluorescence microscopy. Although several methods have been developed for imaging
      brain slices, combining slice culture with the ability to perform repetitive high
      resolution imaging of specific cells in live slices over long time periods has
      posed problems. This is especially true when viral vectors are used for
      expression of exogenous proteins since this is best done in a closed system to
      protect users and prevent cross contamination. Simple modifications made to the
      roller tube brain slice culture method that allow for repetitive high-resolution
      imaging of slices over many weeks in an enclosed system are reported. Culturing
      slices on photoetched coverslips permits the use of fiducial marks to rapidly and
      precisely reposition the stage to image the identical field over time before and
      after different treatments. Examples are shown for the use of this method
      combined with specific neuronal staining and expression to observe changes in
      hippocampal slice architecture, viral-mediated neuronal expression of fluorescent
      proteins, and the development of cofilin pathology, which was previously observed
      in the hippocampus of Alzheimer's disease (AD) in response to slice treatment
      with oligomers of amyloid-beta (Abeta) peptide.

PMID- 29364209
TI  - Dispersion of Nanomaterials in Aqueous Media: Towards Protocol Optimization.
AB  - The sonication process is commonly used for de-agglomerating and dispersing
      nanomaterials in aqueous based media, necessary to improve homogeneity and
      stability of the suspension. In this study, a systematic step-wise approach is
      carried out to identify optimal sonication conditions in order to achieve a
      stable dispersion. This approach has been adopted and shown to be suitable for
      several nanomaterials (cerium oxide, zinc oxide, and carbon nanotubes) dispersed
      in deionized (DI) water. However, with any change in either the nanomaterial type
      or dispersing medium, there needs to be optimization of the basic protocol by
      adjusting various factors such as sonication time, power, and sonicator type as
      well as temperature rise during the process. The approach records the dispersion
      process in detail. This is necessary to identify the time points as well as other
      above-mentioned conditions during the sonication process in which there may be
      undesirable changes, such as damage to the particle surface thus affecting
      surface properties. Our goal is to offer a harmonized approach that can control
      the quality of the final, produced dispersion. Such a guideline is instrumental
      in ensuring dispersion quality repeatability in the nanoscience community,
      particularly in the field of nanotoxicology.

PMID- 29364210
TI  - Studying Diabetes Through the Eyes of a Fish: Microdissection, Visualization, and
      Analysis of the Adult tg(fli:EGFP) Zebrafish Retinal Vasculature.
AB  - Diabetic retinopathy is the leading cause of blindness among middle-aged adults.
      The rising prevalence of diabetes worldwide will make the prevention of diabetic
      microvascular complications one of the key research fields of the next decades.
      Specialized, targeted therapy and novel therapeutic drugs are needed to manage
      the increasing number of patients at risk of vision-loss. The zebrafish is an
      established animal model for developmental research questions with increasing
      relevance for modeling metabolic multifactorial disease processes. The advantages
      of the species allow for optimal visualization and high throughput drug screening
      approaches, combined with the strong ability to knock out genes of interest.
      Here, we describe a protocol which will allow easy analysis of the adult
      tg(fli:EGFP) zebrafish retinal vasculature as a fast read-out in settings of long
      term vascular pathologies linked to neoangiogenesis or vessel damage. This is
      achieved via dissection of the zebrafish retina and whole-mounting of the tissue.
      Visualization of the exposed vessels is then achieved via confocal microscopy of
      the green EGFP reporter expressed in the adult retinal vasculature. Correct
      handling of the tissue will lead to better outcomes and less internal vessel
      breakage to assure the visualization of the unaltered vascular structure. The
      method can be utilized in zebrafish models of retinal vasculopathy linked to
      changes in the vessel architecture as well as neoangiogenesis.

PMID- 29364211
TI  - PET and MRI Guided Irradiation of a Glioblastoma Rat Model Using a Micro
      irradiator.
AB  - For decades, small animal radiation research was mostly performed using fairly
      crude experimental setups applying simple single-beam techniques without the
      ability to target a specific or well-delineated tumor volume. The delivery of
      radiation was achieved using fixed radiation sources or linear accelerators
      producing megavoltage (MV) X-rays. These devices are unable to achieve sub
      millimeter precision required for small animals. Furthermore, the high doses
      delivered to healthy surrounding tissue hamper response assessment. To increase
      the translation between small animal studies and humans, our goal was to mimic
      the treatment of human glioblastoma in a rat model. To enable a more accurate
      irradiation in a preclinical setting, recently, precision image-guided small
      animal radiation research platforms were developed. Similar to human planning
      systems, treatment planning on these micro-irradiators is based on computed
      tomography (CT). However, low soft-tissue contrast on CT makes it very
      challenging to localize targets in certain tissues, such as the brain. Therefore,
      incorporating magnetic resonance imaging (MRI), which has excellent soft-tissue
      contrast compared to CT, would enable a more precise delineation of the target
      for irradiation. In the last decade also biological imaging techniques, such as
      positron emission tomography (PET) gained interest for radiation therapy
      treatment guidance. PET enables the visualization of e.g., glucose consumption,
      amino-acid transport, or hypoxia, present in the tumor. Targeting those highly
      proliferative or radio-resistant parts of the tumor with a higher dose could give
      a survival benefit. This hypothesis led to the introduction of the biological
      tumor volume (BTV), besides the conventional gross target volume (GTV), clinical
      target volume (CTV), and planned target volume (PTV). At the preclinical imaging
      lab of Ghent University, a micro-irradiator, a small animal PET, and a 7 T small
      animal MRI are available. The goal was to incorporate MRI-guided irradiation and
      PET-guided sub-volume boosting in a glioblastoma rat model.

PMID- 29364212
TI  - Whole Genome Sequencing of Candida glabrata for Detection of Markers of
      Antifungal Drug Resistance.
AB  - Candida glabrata can rapidly acquire mutations that result in drug resistance,
      especially to azoles and echinocandins. Identification of genetic mutations is
      essential, as resistance detected in vitro can often be correlated with clinical
      failure. We examined the feasibility of using whole genome sequencing (WGS) for
      genome-wide analysis of antifungal drug resistance in C. glabrata. The aim was
      torecognize enablers and barriers in the implementation WGS and measure its
      effectiveness. This paper outlines the key quality control checkpoints and
      essential components of WGS methodology to investigate genetic markers associated
      with reduced susceptibility to antifungal agents. It also estimates the accuracy
      of data analysis and turn-around-time of testing. Phenotypic susceptibility of 12
      clinical, and one ATCC strain of C. glabrata was determined through antifungal
      susceptibility testing. These included three isolate pairs, from three patients,
      that developed rise in drug minimum inhibitory concentrations. In two pairs, the
      second isolate of each pair developed resistance to echinocandins. The second
      isolate of the third pair developed resistance to 5-flucytosine. The remaining
      comprised of susceptible and azole resistant isolates. Single nucleotide
      polymorphisms (SNPs) in genes linked to echinocandin, azole and 5-flucytosine
      resistance were confirmed in resistant isolates through WGS using the next
      generation sequencing. Non-synonymous SNPs in antifungal resistance genes such as
      FKS1, FKS2, CgPDR1, CgCDR1 and FCY2 were identified. Overall, an average of 98%
      of the WGS reads of C. glabrata isolates mapped to the reference genome with
      about 75-fold read depth coverage. The turnaround time and cost were comparable
      to Sanger sequencing. In conclusion, WGS of C. glabrata was feasible in revealing
      clinically significant gene mutations involved in resistance to different
      antifungal drug classes without the need for multiple PCR/DNA sequencing
      reactions. This represents a positive step towards establishing WGS capability in
      the clinical laboratory for simultaneous detection of antifungal resistance
      conferring substitutions.

PMID- 29364213
TI  - Megakaryocyte Differentiation and Platelet Formation from Human Cord Blood
      derived CD34+ Cells.
AB  - Platelet production occurs principally in the bone marrow in a process known as
      thrombopoiesis. During thrombopoiesis, hematopoietic progenitor cells
      differentiate to form platelet precursors called megakaryocytes, which terminally
      differentiate to release platelets from long cytoplasmic processes termed
      proplatelets. Megakaryocytes are rare cells confined to the bone marrow and are
      therefore difficult to harvest in sufficient numbers for laboratory use.
      Efficient production of human megakaryocytes can be achieved in vitro by
      culturing CD34+ cells under suitable conditions. The protocol detailed here
      describes isolation of CD34+ cells by magnetic cell sorting from umbilical cord
      blood samples. The necessary steps to produce highly pure, mature megakaryocytes
      under serum-free conditions are described. Details of phenotypic analysis of
      megakaryocyte differentiation and determination of proplatelet formation and
      platelet production are also provided. Effectors that influence megakaryocyte
      differentiation and/or proplatelet formation, such as anti-platelet antibodies or
      thrombopoietin mimetics, can be added to cultured cells to examine biological
      function.

PMID- 29364214
TI  - Assessment of Antibody-based Drugs Effects on Murine Bone Marrow and Peritoneal
      Macrophage Activation.
AB  - Macrophages are phagocytic innate immune cells, which initiate immune responses
      to pathogens and contribute to healing and tissue restitution. Macrophages are
      equally important in turning off inflammatory responses. We have shown that
      macrophages stimulated with intravenous immunoglobulin (IVIg) can produce high
      amounts of the anti-inflammatory cytokine, interleukin 10 (IL-10), and low levels
      of pro-inflammatory cytokines in response to bacterial lipopolysaccharides (LPS).
      IVIg is a polyvalent antibody, primarily immunoglobulin Gs (IgGs), pooled from
      the plasma of more than 1,000 blood donors. It is used to supplement antibodies
      in patients with immune deficiencies or to suppress immune responses in patients
      with autoimmune or inflammatory conditions. Infliximab, a therapeutic anti-tumor
      necrosis factor alpha (TNFalpha) antibody, has also been shown to activate
      macrophages to produce IL-10 in response to inflammatory stimuli. IVIg and other
      antibody-based biologics can be tested to determine their effects on macrophage
      activation. This paper describes methods for derivation, stimulation, and
      assessment of murine bone marrow macrophages activated by antibodies in vitro and
      murine peritoneal macrophages activated with antibodies in vivo. Finally, we
      demonstrate the use of western blotting to determine the contribution of specific
      cell signaling pathways to anti-inflammatory macrophage activity. These protocols
      can be used with genetically modified mice, to determine the effect of a specific
      protein(s) on anti-inflammatory macrophage activation. These techniques can also
      be used to assess whether specific biologics may act by changing macrophages to
      an IL-10-producing anti-inflammatory activation state that reduces inflammatory
      responses in vivo. This can provide information on the role of macrophage
      activation in the efficacy of biologics during disease models in mice, and
      provide insight into a potential new mechanism of action in people. Conversely,
      this may caution against the use of specific antibody-based biologics to treat
      infectious disease, particularly if macrophages play an important role in host
      defense against that infection.

PMID- 29364215
TI  - Mass Isolation and In Vitro Cultivation of Intramolluscan Stages of the Human
      Blood Fluke Schistosoma Mansoni.
AB  - Human blood flukes, Schistosoma spp., have a complex life cycle that involves
      asexual and sexual developmental phases within a snail intermediate and mammalian
      final host, respectively. The ability to isolate and sustain the different life
      cycle stages under in vitro culture conditions has greatly facilitated
      investigations of the cellular, biochemical and molecular mechanisms regulating
      parasite growth, development and host interactions. Transmission of
      schistosomiasis requires asexual reproduction and development of multiple larval
      stages within the snail host; from the infective miracidium, through primary and
      secondary sporocysts, to the final cercarial stage that is infective to humans.
      In this paper we present a step-by-step protocol for mass hatching and isolation
      of Schistosoma mansoni miracidia from eggs obtained from livers of infected mice,
      and their subsequent introduction into in vitro culture. It is anticipated that
      the detailed protocol will encourage new researchers to engage in and broaden
      this important field of schistosome research.

PMID- 29364216
TI  - Bioprinting of Cartilage and Skin Tissue Analogs Utilizing a Novel Passive Mixing
      Unit Technique for Bioink Precellularization.
AB  - Bioprinting is a powerful technique for the rapid and reproducible fabrication of
      constructs for tissue engineering applications. In this study, both cartilage and
      skin analogs were fabricated after bioink pre-cellularization utilizing a novel
      passive mixing unit technique. This technique was developed with the aim to
      simplify the steps involved in the mixing of a cell suspension into a highly
      viscous bioink. The resolution of filaments deposited through bioprinting
      necessitates the assurance of uniformity in cell distribution prior to printing
      to avoid the deposition of regions without cells or retention of large cell
      clumps that can clog the needle. We demonstrate the ability to rapidly blend a
      cell suspension with a bioink prior to bioprinting of both cartilage and skin
      analogs. Both tissue analogs could be cultured for up to 4 weeks. Histological
      analysis demonstrated both cell viability and deposition of tissue specific
      extracellular matrix (ECM) markers such as glycosaminoglycans (GAGs) and collagen
      I respectively.

PMID- 29364217
TI  - A Novel Method for Involving Women of Color at High Risk for Preterm Birth in
      Research Priority Setting.
AB  - Involvement of patients and the public is now recognized to be essential for the
      good conduct of research. Patient and public involvement in research priority
      setting and funding decisions is only beginning to be recognized as important,
      and methods for doing so are nascent. This protocol describes the Research
      Prioritization by Affected Communities (RPAC) protocol and findings from its use
      with women at high socio-demographic risk for preterm birth. The goal was to
      directly involve these women in identifying and prioritizing their unanswered
      questions about pregnancy, birth and neonatal care, and treatment so that their
      views could be included in research priority setting by funders and researchers.
      The RPAC protocol may be used to meaningfully involve under-represented groups at
      high-risk for specific health problems, or those who face disproportionate burden
      of disease, in research strategy and funding priority setting.

PMID- 29364218
TI  - Production of Genetically Engineered Golden Syrian Hamsters by Pronuclear
      Injection of the CRISPR/Cas9 Complex.
AB  - The pronuclear (PN) injection technique was first established in mice to
      introduce foreign genetic materials into the pronuclei of one-cell stage embryos.
      The introduced genetic material may integrate into the embryonic genome and
      generate transgenic animals with foreign genetic information following transfer
      of the injected embryos to foster mothers. Following the success in mice, PN
      injection has been applied successfully in many other animal species. Recently,
      PN injection has been successfully employed to introduce reagents with gene
      modifying activities, such as the CRISPR/Cas9 system, to achieve site-specific
      genetic modifications in several laboratory and farm animal species. In addition
      to mastering the special set of microinjection skills to produce genetically
      modified animals by PN injection, researchers must understand the reproduction
      physiology and behavior of the target species, because each species presents
      unique challenges. For example, golden Syrian hamster embryos have unique
      handling requirements in vitro such that PN injection techniques were not
      possible in this species until recent breakthroughs by our group. With our
      species-modified PN injection protocol, we have succeeded in producing several
      gene knockout (KO) and knockin (KI) hamsters, which have been used successfully
      to model human diseases. Here we describe the PN injection procedure for
      delivering the CRISPR/Cas9 complex to the zygotes of the hamster, the embryo
      handling conditions, embryo transfer procedures, and husbandry required to
      produce genetically modified hamsters.

PMID- 29364219
TI  - Discovering Middle Ear Anatomy by Transcanal Endoscopic Ear Surgery: A Dissection
      Manual.
AB  - The middle ear is located in the center of the temporal bone and bears a highly
      complex anatomy. The recently introduced exclusively endoscopic transcanal
      approach to the middle ear is a minimally invasive technique sparing the bone and
      mucosa of the mastoid bone, since the middle ear is accessed through the external
      auditory canal. This emerging method has several advantages over the traditional
      (microscopic) approaches to the middle ear such as the panoramic wide-angle views
      of the anatomy, the possibility to approach and magnify tiny structures, and the
      possibility of looking around the corner using angled endoscopes. The cadaveric
      dissection method presented here consists of an overview on the technical
      requirements and a precise description of a step-by-step protocol to discover the
      anatomy of the middle ear. Each step and anatomical structure is carefully
      described in order to provide a comprehensive guide to endoscopic ear anatomy. In
      our opinion, this is particularly important to any novice in endoscopic ear
      surgery as it provides thorough anatomical knowledge and may improve surgical
      skills.

PMID- 29364220
TI  - Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a
      Continuous Drug Infusion System into the Mouse Brain.
AB  - Insulin regulates systematic metabolism in the hypothalamus and the peripheral
      insulin response. An inflammatory reaction in peripheral adipose tissues
      contributes to type 2 diabetes mellitus (T2DM) development and appetite
      regulation in the hypothalamus. Chemokine CCL5 and C-C chemokine receptor type 5
      (CCR5) levels have been suggested to mediate arteriosclerosis and glucose
      intolerance in type 2 diabetes mellitus (T2DM). In addition, CCL5 plays a
      neuroendocrine role in the hypothalamus by regulating food intake and body
      temperature, thus, prompting us to investigate its function in hypothalamic
      insulin signaling and the regulation of peripheral glucose metabolism. The micro
      osmotic pump brain infusion system is a quick and precise way to manipulate CCL5
      function and study its effect in the brain. It also provides a convenient
      alternative approach to generating a transgenic knockout animal. In this system,
      CCL5 signaling was blocked by intracerebroventricular (ICV) infusion of its
      antagonist, MetCCL5, using a micro-osmotic pump. The peripheral glucose
      metabolism and insulin responsiveness was detected by the Oral Glucose Tolerance
      Test (OGTT) and Insulin Tolerance Test (ITT). Insulin signaling activity was then
      analyzed by protein blot from tissue samples derived from the animals. After 7-14
      days of MetCCL5 infusion, the glucose metabolism and insulin responsiveness was
      impaired in mice, as seen in the results of the OGTT and ITT. The IRS-1 serine302
      phosphorylation was increased and the Akt activity was reduced in mice
      hypothalamic neurons following CCL5 inhibition. Altogether, our data suggest that
      blocking CCL5 in the mouse brain increases the phosphorylation of IRS-1 S302 and
      interrupts hypothalamic insulin signaling, leading to a decrease in insulin
      function in peripheral tissues as well as the impairment of glucose metabolism.

PMID- 29364221
TI  - Hydrodynamic Renal Pelvis Injection for Non-viral Expression of Proteins in the
      Kidney.
AB  - Hydrodynamic injection creates a local, high-pressure environment to transfect
      various tissues with plasmid DNA and other substances. Hydrodynamic tail vein
      injection, for example, is a well-established method by which the liver can be
      transfected. This manuscript describes an application of hydrodynamic principles
      by injection of the mouse kidney directly with plasmid DNA for kidney-specific
      gene expression. Mice are anesthetized and the kidney is exposed by a flank
      incision followed by a fast injection of a plasmid DNA-containing solution
      directly into the renal pelvis. The needle is kept in place for ten seconds and
      the incision site is sutured. The following day, live animal imaging, Western
      blot, or immunohistochemistry may be used to assay gene expression, or other
      assays suited to the transgene of choice are used for detection of the protein of
      interest. Published methods to prolong gene expression include transposon
      mediated transgene integration and cyclophosphamide treatment to inhibit the
      immune response to the transgene.

PMID- 29364222
TI  - Microfluidic Devices for Characterizing Pore-scale Event Processes in Porous
      Media for Oil Recovery Applications.
AB  - Microfluidic devices are versatile tools for studying transport processes at a
      microscopic scale. A demand exists for microfluidic devices that are resistant to
      low molecular-weight oil components, unlike traditional polydimethylsiloxane
      (PDMS) devices. Here, we demonstrate a facile method for making a device with
      this property, and we use the product of this protocol for examining the pore
      scale mechanisms by which foam recovers crude oil. A pattern is first designed
      using computer-aided design (CAD) software and printed on a transparency with a
      high-resolution printer. This pattern is then transferred to a photoresist via a
      lithography procedure. PDMS is cast on the pattern, cured in an oven, and removed
      to obtain a mold. A thiol-ene crosslinking polymer, commonly used as an optical
      adhesive (OA), is then poured onto the mold and cured under UV light. The PDMS
      mold is peeled away from the optical adhesive cast. A glass substrate is then
      prepared, and the two halves of the device are bonded together. Optical adhesive
      based devices are more robust than traditional PDMS microfluidic devices. The
      epoxy structure is resistant to swelling by many organic solvents, which opens
      new possibilities for experiments involving light organic liquids. Additionally,
      the surface wettability behavior of these devices is more stable than that of
      PDMS. The construction of optical adhesive microfluidic devices is simple, yet
      requires incrementally more effort than the making of PDMS-based devices. Also,
      though optical adhesive devices are stable in organic liquids, they may exhibit
      reduced bond-strength after a long time. Optical adhesive microfluidic devices
      can be made in geometries that act as 2-D micromodels for porous media. These
      devices are applied in the study of oil displacement to improve our understanding
      of the pore-scale mechanisms involved in enhanced oil recovery and aquifer
      remediation.

PMID- 29364223
TI  - Application of High-speed Super-resolution SPEED Microscopy in Live Primary
      Cilium.
AB  - The primary cilium is a microtubule-based protrusion on the surface of many
      eukaryotic cells and contains a unique complement of proteins that function
      critically in cell motility and signaling. Since cilia are incapable of
      synthesizing their own protein, nearly 200 unique ciliary proteins need to be
      trafficked between the cytosol and primary cilia. However, it is still a
      technical challenge to map three-dimensional (3D) locations of transport pathways
      for these proteins in live primary cilia due to the limitations of currently
      existing techniques. To conquer the challenge, recently we have developed and
      employed a high-speed virtual 3D super-resolution microscopy, termed single-point
      edge-excitation sub-diffraction (SPEED) microscopy, to determine the 3D spatial
      location of transport pathways for both cytosolic and membrane proteins in
      primary cilia of live cells. In this article, we will demonstrate the detailed
      setup of SPEED microscopy, the preparation of cells expressing fluorescence
      protein-labeled ciliary proteins, the real-time single-molecule tracking of
      individual proteins in live cilium and the achievement of 3D spatial probability
      density maps of transport routes for ciliary proteins.

PMID- 29364224
TI  - A Method for Obtaining Serial Ultrathin Sections of Microorganisms in
      Transmission Electron Microscopy.
AB  - Observing cells and cell components in three dimensions at high magnification in
      transmission electron microscopy requires preparing serial ultrathin sections of
      the specimen. Although preparing serial ultrathin sections is considered to be
      very difficult, it is rather easy if the proper method is used. In this paper, we
      show a step-by-step procedure for safely obtaining serial ultrathin sections of
      microorganisms. The key points of this method are: 1) to use the large part of
      the specimen and adjust the specimen surface and knife edge so that they are
      parallel to each other; 2) to cut serial sections in groups and avoid difficulty
      in separating sections using a pair of hair strands when retrieving a group of
      serial sections onto the slit grids; 3) to use a 'Section-holding loop' and avoid
      mixing up the order of the section groups; 4) to use a 'Water-surface-raising
      loop' and make sure the sections are positioned on the apex of the water and that
      they touch the grid first, in order to place them in the desired position on the
      grids; 5) to use the support film on an aluminum rack and make it easier to
      recover the sections on the grids and to avoid wrinkling of the support film; and
      6) to use a staining tube and avoid accidentally breaking the support films with
      tweezers. This new method enables obtaining serial ultrathin sections without
      difficulty. The method makes it possible to analyze cell structures of
      microorganisms at high resolution in 3D, which cannot be achieved by using the
      automatic tape-collecting ultramicrotome method and serial block-face or focused
      ion beam scanning electron microscopy.

PMID- 29364225
TI  - Analyzing the Communication Between Monocytes and Primary Breast Cancer Cells in
      an Extracellular Matrix Extract (ECME)-based Three-dimensional System.
AB  - Embedded in the extracellular matrix (ECM), normal and neoplastic epithelial
      cells intimately communicate with hematopoietic and non-hematopoietic cells, thus
      greatly influencing normal tissue homeostasis and disease outcome. In breast
      cancer, tumor-associated macrophages (TAMs) play a critical role in disease
      progression, metastasis, and recurrence; therefore, understanding the mechanisms
      of monocyte chemoattraction to the tumor microenvironment and their interactions
      with tumor cells is important to control the disease. Here, we provide a detailed
      description of a three-dimensional (3D) co-culture system of human breast cancer
      (BrC) cells and human monocytes. BrC cells produced high basal levels of
      regulated on-activation, normal T-cell expressed and secreted (RANTES), monocyte
      chemoattractant protein-1 (MCP-1), and granulocyte-macrophage colony-stimulating
      factor (G-CSF), while in co-culture with monocytes, pro-inflammatory cytokines
      Interleukin (IL)-1 beta (IL-1beta) and IL-8 were enriched together with matrix
      metalloproteinases (MMP)-1, MMP-2, and MMP-10. This tumor stroma microenvironment
      promoted resistance to anoikis in MCF-10A 3D acini-like structures,
      chemoattraction of monocytes, and invasion of aggressive BrC cells. The protocols
      presented here provide an affordable alternative to study intra-tumor
      communication and are an example of the great potential that in vitro 3D cell
      systems provide to interrogate specific features of tumor biology related to
      tumor aggression.

PMID- 29364226
TI  - Metabolic Labeling and Profiling of Transfer RNAs Using Macroarrays.
AB  - Transfer RNAs (tRNA) are abundant short non-coding RNA species that are typically
      76 to 90 nucleotides in length. tRNAs are directly responsible for protein
      synthesis by translating codons in mRNA into amino acid sequences. tRNAs were
      long considered as house-keeping molecules that lacked regulatory functions.
      However, a growing body of evidence indicates that cellular tRNA levels fluctuate
      in correspondence to varying conditions such as cell type, environment, and
      stress. The fluctuation of tRNA expression directly influences gene translation,
      favoring or repressing the expression of particular proteins. Ultimately
      comprehending the dynamic of protein synthesis requires the development of
      methods able to deliver high-quality tRNA profiles. The method that we present
      here is named SPOt, which stands for Streamlined Platform for Observing tRNA.
      SPOt consists of three steps starting with metabolic labeling of cell cultures
      with radioactive orthophosphate, followed by guanidinium thiocyanate-phenol
      chloroform extraction of radioactive total RNAs and finally hybridization on in
      house printed macroarrays. tRNA levels are estimated by quantifying the
      radioactivity intensities at each probe spot. In the protocol presented here we
      profile tRNAs in Mycobacterium smegmatis mc2155, a nonpathogenic bacterium often
      used as a model organism to study tuberculosis.

PMID- 29364227
TI  - One-pot Microwave-assisted Conversion of Anomeric Nitrate-esters to
      Trichloroacetimidates.
AB  - The goal of the following procedure is to provide a demonstration of the one-pot
      conversion of a 2-azido-1-nitrate-ester to a trichloroacetimidate glycosyl donor.
      Following azido-nitration of a glycal, the product 2-azido-1-nitrate ester can be
      hydrolyzed under microwave-assisted irradiation. This transformation is usually
      achieved using strongly nucleophilic reagents and extended reaction times.
      Microwave irradiation induces hydrolysis, in the absence of reagents, with short
      reaction times. Following denitration, the intermediate anomeric alcohol is
      converted, in the same pot, to the corresponding 2-azido-1-trichloroacetimidate.

PMID- 29364228
TI  - The Calibration and Use of Capacitance Sensors to Monitor Stem Water Content in
      Trees.
AB  - Water transport and storage through the soil-plant-atmosphere continuum is
      critical to the terrestrial water cycle, and has become a major research focus
      area. Biomass capacitance plays an integral role in the avoidance of hydraulic
      impairment to transpiration. However, high temporal resolution measurements of
      dynamic changes in the hydraulic capacitance of large trees are rare. Here, we
      present procedures for the calibration and use of capacitance sensors, typically
      used to monitor soil water content, to measure the volumetric water content in
      trees in the field. Frequency domain reflectometry-style observations are
      sensitive to the density of the media being studied. Therefore, it is necessary
      to perform species-specific calibrations to convert from the sensor-reported
      values of dielectric permittivity to volumetric water content. Calibration is
      performed on a harvested branch or stem cut into segments that are dried or re
      hydrated to produce a full range of water contents used to generate a best-fit
      regression with sensor observations. Sensors are inserted into calibration
      segments or installed in trees after pre-drilling holes to a tolerance fit using
      a fabricated template to ensure proper drill alignment. Special care is taken to
      ensure that sensor tines make good contact with the surrounding media, while
      allowing them to be inserted without excessive force. Volumetric water content
      dynamics observed via the presented methodology align with sap flow measurements
      recorded using thermal dissipation techniques and environmental forcing data.
      Biomass water content data can be used to observe the onset of water stress,
      drought response and recovery, and has the potential to be applied to the
      calibration and evaluation of new plant-level hydrodynamics models, as well as to
      the partitioning of remotely sensed moisture products into above- and belowground
      components.

PMID- 29364229
TI  - Isolation and Respiratory Measurements of Mitochondria from Arabidopsis thaliana.
AB  - Mitochondria are essential organelles involved in numerous metabolic pathways in
      plants, most notably the production of adenosine triphosphate (ATP) from the
      oxidation of reduced compounds such as nicotinamide adenine dinucleotide (NADH)
      and flavin adenine dinucleotide (FADH2). The complete annotation of the
      Arabidopsis thaliana genome has established it as the most widely used plant
      model system, and thus the need to purify mitochondria from a variety of organs
      (leaf, root, or flower) is necessary to fully utilize the tools that are now
      available for Arabidopsis to study mitochondrial biology. Mitochondria are
      isolated by homogenization of the tissue using a variety of approaches, followed
      by a series of differential centrifugation steps producing a crude mitochondrial
      pellet that is further purified using continuous colloidal density gradient
      centrifugation. The colloidal density material is subsequently removed by
      multiple centrifugation steps. Starting from 100 g of fresh leaf tissue, 2 - 3 mg
      of mitochondria can be routinely obtained. Respiratory experiments on these
      mitochondria display typical rates of 100 - 250 nmol O2 min-1 mg total
      mitochondrial protein-1 (NADH-dependent rate) with the ability to use various
      substrates and inhibitors to determine which substrates are being oxidized and
      the capacity of the alternative and cytochrome terminal oxidases. This protocol
      describes an isolation method of mitochondria from Arabidopsis thaliana leaves
      using continuous colloidal density gradients and an efficient respiratory
      measurements of purified plant mitochondria.

PMID- 29364230
TI  - Application of RNAi and Heat-shock-induced Transcription Factor Expression to
      Reprogram Germ Cells to Neurons in C. elegans.
AB  - Studying the cell biological processes during converting the identities of
      specific cell types provides important insights into mechanism that maintain and
      protect cellular identities. The conversion of germ cells into specific neurons
      in the nematode Caenorhabditis elegans (C. elegans) is a powerful tool for
      performing genetic screens in order to dissect regulatory pathways that safeguard
      established cell identities. Reprogramming of germ cells to a specific type of
      neurons termed ASE requires transgenic animals that allow broad over-expression
      of the Zn-finger transcription factor (TF) CHE-1. Endogenous CHE-1 is expressed
      exclusively in two head neurons and is required to specify the glutamatergic ASE
      neurons fate, which can easily be visualized by the gcy-5prom::gfp reporter. A
      trans gene containing the heat-shock promoter-driven che-1 gene expression
      construct allows broad mis-expression of CHE-1 in the entire animal upon heat
      shock treatment. The combination of RNAi against the chromatin-regulating factor
      LIN-53 and heat-shock-induced che-1 over-expression leads to reprogramming of
      germ cell into ASE neuron-like cells. We describe here the specific RNAi
      procedure and appropriate conditions for heat-shock treatment of transgenic
      animals in order to successfully induce germ cell to neuron conversion.

PMID- 29364231
TI  - Embryo Microinjection and Transplantation Technique for Nasonia vitripennis
      Genome Manipulation.
AB  - The jewel wasp Nasonia vitripennis has emerged as an effective model system for
      the study of processes including sex determination, haplo-diploid sex
      determination, venom synthesis, and host-symbiont interactions, among others. A
      major limitation of working with this organism is the lack of effective protocols
      to perform directed genome modifications. An important part of genome
      modification is delivery of editing reagents, including CRISPR/Cas9 molecules,
      into embryos through microinjection. While microinjection is well established in
      many model organisms, this technique is particularly challenging to perform in N.
      vitripennis primarily due to its small embryo size, and the fact that embryonic
      development occurs entirely within a parasitized blowfly pupa. The following
      procedure overcomes these significant challenges while demonstrating a
      streamlined, visual procedure for effectively removing wasp embryos from
      parasitized host pupae, microinjecting them, and carefully transplanting them
      back into the host for continuation and completion of development. This protocol
      will strongly enhance the capability of research groups to perform advanced
      genome modifications in this organism.

PMID- 29364232
TI  - Recording Brain Electromagnetic Activity During the Administration of the Gaseous
      Anesthetic Agents Xenon and Nitrous Oxide in Healthy Volunteers.
AB  - Anesthesia arguably provides one of the only systematic ways to study the neural
      correlates of global consciousness/unconsciousness. However to date most
      neuroimaging or neurophysiological investigations in humans have been confined to
      the study of gamma-Amino-Butyric-Acid-(GABA)-receptor-agonist-based anesthetics,
      while the effects of dissociative N-Methyl-D-Aspartate-(NMDA)-receptor-antagonist
      based anesthetics ketamine, nitrous oxide (N2O) and xenon (Xe) are largely
      unknown. This paper describes the methods underlying the simultaneous recording
      of magnetoencephalography (MEG) and electroencephalography (EEG) from healthy
      males during inhalation of the gaseous anesthetic agents N2O and Xe. Combining
      MEG and EEG data enables the assessment of electromagnetic brain activity during
      anesthesia at high temporal, and moderate spatial, resolution. Here we describe a
      detailed protocol, refined over multiple recording sessions, that includes
      subject recruitment, anesthesia equipment setup in the MEG scanner room, data
      collection and basic data analysis. In this protocol each participant is exposed
      to varying levels of Xe and N2O in a repeated measures cross-over design.
      Following relevant baseline recordings participants are exposed to step-wise
      increasing inspired concentrations of Xe and N2O of 8, 16, 24 and 42%, and 16, 32
      and 47% respectively, during which their level of responsiveness is tracked with
      an auditory continuous performance task (aCPT). Results are presented for a
      number of recordings to highlight the sensor-level properties of the raw data,
      the spectral topography, the minimization of head movements, and the unequivocal
      level dependent effects on the auditory evoked responses. This paradigm describes
      a general approach to the recording of electromagnetic signals associated with
      the action of different kinds of gaseous anesthetics, which can be readily
      adapted to be used with volatile and intravenous anesthetic agents. It is
      expected that the method outlined can contribute to the understanding of the
      macro-scale mechanisms of anesthesia by enabling methodological extensions
      involving source space imaging and functional network analysis.

PMID- 29364233
TI  - A Novel Feeder-free System for Mass Production of Murine Natural Killer Cells In
      Vitro.
AB  - Natural killer (NK) cells belong to the innate immune system and are a first-line
      anti-cancer immune defense; however, they are suppressed in the tumor
      microenvironment and the underlying mechanism is still largely unknown. The lack
      of a consistent and reliable source of NK cells limits the research progress of
      NK cell immunity. Here, we report an in vitro system that can provide high
      quality and quantity of bone marrow-derived murine NK cells under a feeder-free
      condition. More importantly, we also demonstrate that siRNA-mediated gene
      silencing successfully inhibits the E4bp4-dependent NK cell maturation by using
      this system. Thus, this novel in vitro NK cell differentiating system is a
      biomaterial solution for immunity research.

PMID- 29364234
TI  - Measuring Deformability and Red Cell Heterogeneity in Blood by Ektacytometry.
AB  - Decreased red cell deformability is characteristic of several disorders. In some
      cases, the extent of defective deformability can predict severity of disease or
      occurrence of serious complications. Ektacytometry uses laser diffraction
      viscometry to measure the deformability of red blood cells subject to either
      increasing shear stress or an osmotic gradient at a constant value of applied
      shear stress. However, direct deformability measurements are difficult to
      interpret when measuring heterogenous blood that is characterized by the presence
      of both rigid and deformable red cells. This is due to the inability of rigid
      cells to properly align in response to shear stress and results in a distorted
      diffraction pattern marked by an exaggerated decrease in apparent deformability.
      Measurement of the degree of distortion provides an indicator of the
      heterogeneity of the erythrocytes in blood. In sickle cell anemia, this is
      correlated with the percentage of rigid cells, which reflects the hemoglobin
      concentration and hemoglobin composition of the erythrocytes. In addition to
      measuring deformability, osmotic gradient ektacytometry provides information
      about the osmotic fragility and hydration status of erythrocytes. These
      parameters also reflect the hemoglobin composition of red blood cells from sickle
      cell patients. Ektacytometry measures deformability in populations of red cells
      and does not, therefore, provide information on the deformability or mechanical
      properties of individual erythrocytes. Regardless, the goal of the techniques
      described herein is to provide a convenient and reliable method for measuring the
      deformability and cellular heterogeneity of blood. These techniques may be useful
      for monitoring temporal changes, as well as disease progression and response to
      therapeutic intervention in several disorders. Sickle cell anemia is one well
      characterized example. Other potential disorders where measurements of red cell
      deformability and/or heterogeneity are of interest include blood storage,
      diabetes, Plasmodium infection, iron deficiency, and the hemolytic anemias due to
      membrane defects.

PMID- 29364235
TI  - Fabrication Procedures and Birefringence Measurements for Designing Magnetically
      Responsive Lanthanide Ion Chelating Phospholipid Assemblies.
AB  - Bicelles are tunable disk-like polymolecular assemblies formed from a large
      variety of lipid mixtures. Applications range from membrane protein structural
      studies by nuclear magnetic resonance (NMR) to nanotechnological developments
      including the formation of optically active and magnetically switchable gels.
      Such technologies require high control of the assembly size, magnetic response
      and thermal resistance. Mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC) and its lanthanide ion (Ln3+) chelating phospholipid conjugate, 1,2
      dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate
      (DMPE-DTPA), assemble into highly magnetically responsive assemblies such as
      DMPC/DMPE-DTPA/Ln3+ (molar ratio 4:1:1) bicelles. Introduction of cholesterol
      (Chol-OH) and steroid derivatives in the bilayer results in another set of
      assemblies offering unique physico-chemical properties. For a given lipid
      composition, the magnetic alignability is proportional to the bicelle size. The
      complexation of Ln3+ results in unprecedented magnetic responses in terms of both
      magnitude and alignment direction. The thermo-reversible collapse of the disk
      like structures into vesicles upon heating allows tailoring of the assemblies'
      dimensions by extrusion through membrane filters with defined pore sizes. The
      magnetically alignable bicelles are regenerated by cooling to 5  degrees C,
      resulting in assembly dimensions defined by the vesicle precursors. Herein, this
      fabrication procedure is explained and the magnetic alignability of the
      assemblies is quantified by birefringence measurements under a 5.5 T magnetic
      field. The birefringence signal, originating from the phospholipid bilayer,
      further enables monitoring of polymolecular changes occurring in the bilayer.
      This simple technique is complementary to NMR experiments that are commonly
      employed to characterize bicelles.

PMID- 29364236
TI  - Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent
      Human Fibroblasts.
AB  - Quiescence is a temporary, reversible state in which cells have ceased cell
      division, but retain the capacity to proliferate. Multiple studies, including
      ours, have demonstrated that quiescence is associated with widespread changes in
      gene expression. Some of these changes occur through changes in the level or
      activity of proliferation-associated transcription factors, such as E2F and MYC.
      We have demonstrated that mRNA decay can also contribute to changes in gene
      expression between proliferating and quiescent cells. In this protocol, we
      describe the procedure for establishing proliferating and quiescent cultures of
      human dermal foreskin fibroblasts. We then describe the procedures for inhibiting
      new transcription in proliferating and quiescent cells with Actinomycin D (ActD).
      ActD treatment represents a straightforward and reproducible approach to
      dissociating new transcription from transcript decay. A disadvantage of ActD
      treatment is that the time course must be limited to a short time frame because
      ActD affects cell viability. Transcript levels are monitored over time to
      determine transcript decay rates. This procedure allows for the identification of
      genes and isoforms that exhibit differential decay in proliferating versus
      quiescent fibroblasts.

PMID- 29364237
TI  - Chromatin Immunoprecipitation (ChIP) of Histone Modifications from Saccharomyces
      cerevisiae.
AB  - Histone post-translational modifications (PTMs), such as acetylation, methylation
      and phosphorylation, are dynamically regulated by a series of enzymes that add or
      remove these marks in response to signals received by the cell. These PTMS are
      key contributors to the regulation of processes such as gene expression control
      and DNA repair. Chromatin immunoprecipitation (chIP) has been an instrumental
      approach for dissecting the abundance and localization of many histone PTMs
      throughout the genome in response to diverse perturbations to the cell. Here, a
      versatile method for performing chIP of post-translationally modified histones
      from the budding yeast Saccharomyces cerevisiae (S. cerevisiae) is described.
      This method relies on crosslinking of proteins and DNA using formaldehyde
      treatment of yeast cultures, generation of yeast lysates by bead beating,
      solubilization of chromatin fragments by micrococcal nuclease, and
      immunoprecipitation of histone-DNA complexes. DNA associated with the histone
      mark of interest is purified and subjected to quantitative PCR analysis to
      evaluate its enrichment at multiple loci throughout the genome. Representative
      experiments probing the localization of the histone marks H3K4me2 and H4K16ac in
      wildtype and mutant yeast are discussed to demonstrate data analysis and
      interpretation. This method is suitable for a variety of histone PTMs and can be
      performed with different mutant strains or in the presence of diverse
      environmental stresses, making it an excellent tool for investigating changes in
      chromatin dynamics under different conditions.

PMID- 29364238
TI  - Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and
      Subsequent Conversion to Substituted Phthalans and Phenethylamines.
AB  - Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the
      presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides,
      which react under a variety of conditions to afford useful N- and O-containing
      compounds. Acid-catalyzed addition of alcohols or thiols to N-(2
      alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and
      thioketals, respectively. Selective reduction of the vinyl group in N-(2
      alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the
      corresponding phthalan in good yield, whereas reduction with sodium bis(2
      methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue.
      Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically
      versatile, but often hydrolytically unstable, this protocol emphasizes key
      techniques in preparing, handling, and reacting these pivotal substrates in
      several useful transformations.

PMID- 29364239
TI  - Cell Aggregation Assays to Evaluate the Binding of the Drosophila Notch with
      Trans-Ligands and its Inhibition by Cis-Ligands.
AB  - Notch signaling is an evolutionarily conserved cell-cell communication system
      used broadly in animal development and adult maintenance. Interaction of the
      Notch receptor with ligands from neighboring cells induces activation of the
      signaling pathway (trans-activation), while interaction with ligands from the
      same cell inhibits signaling (cis-inhibition). Proper balance between trans
      activation and cis-inhibition helps establish optimal levels of Notch signaling
      in some contexts during animal development. Because of the overlapping expression
      domains of Notch and its ligands in many cell types and the existence of feedback
      mechanisms, studying the effects of a given post-translational modification on
      trans- versus cis-interactions of Notch and its ligands in vivo is difficult.
      Here, we describe a protocol for using Drosophila S2 cells in cell-aggregation
      assays to assess the effects of knocking down a Notch pathway modifier on the
      binding of Notch to each ligand in trans and in cis. S2 cells stably or
      transiently transfected with a Notch-expressing vector are mixed with cells
      expressing each Notch ligand (S2-Delta or S2-Serrate). Trans-binding between the
      receptor and ligands results in the formation of heterotypic cell aggregates and
      is measured in terms of the number of aggregates per mL composed of >6 cells. To
      examine the inhibitory effect of cis-ligands, S2 cells co-expressing Notch and
      each ligand are mixed with S2-Delta or S2-Serrate cells and the number of
      aggregates is quantified as described above. The relative decrease in the number
      of aggregates due to the presence of cis-ligands provides a measure of cis-ligand
      mediated inhibition of trans-binding. These straightforward assays can provide
      semi-quantitative data on the effects of genetic or pharmacological manipulations
      on the binding of Notch to its ligands, and can help deciphering the molecular
      mechanisms underlying the in vivo effects of such manipulations on Notch
      signaling.

PMID- 29364240
TI  - Cell Membrane Repair Assay Using a Two-photon Laser Microscope.
AB  - Numerous pathophysiological insults can cause damage to cell membranes and, when
      coupled with innate defects in cell membrane repair or integrity, can result in
      disease. Understanding the underlying molecular mechanisms surrounding cell
      membrane repair is, therefore, an important objective to the development of novel
      therapeutic strategies for diseases associated with dysfunctional cell membrane
      dynamics. Many in vitro and in vivo studies aimed at understanding cell membrane
      resealing in various disease contexts utilize two-photon laser ablation as a
      standard for determining functional outcomes following experimental treatments.
      In this assay, cell membranes are subjected to wounding with a two-photon laser,
      which causes the cell membrane to rupture and fluorescent dye to infiltrate the
      cell. The intensity of fluorescence within the cell can then be monitored to
      quantify the cell's ability to reseal itself. There are several alternative
      methods for assessing cell membrane response to injury, as well as great
      variation in the two-photon laser wounding approach itself, therefore, a single,
      unified model of cell wounding would beneficially serve to decrease the variation
      between these methodologies. In this article, we outline a simple two-photon
      laser wounding protocol for assessing cell membrane repair in vitro in both
      healthy and dysferlinopathy patient fibroblast cells transfected with or without
      a full-length dysferlin plasmid.

PMID- 29364241
TI  - Combining X-Ray Crystallography with Small Angle X-Ray Scattering to Model
      Unstructured Regions of Nsa1 from S. Cerevisiae.
AB  - Determination of the full-length structure of ribosome assembly factor Nsa1 from
      Saccharomyces cerevisiae (S. cerevisiae) is challenging because of the disordered
      and protease labile C-terminus of the protein. This manuscript describes the
      methods to purify recombinant Nsa1 from S. cerevisiae for structural analysis by
      both X-ray crystallography and SAXS. X-ray crystallography was utilized to solve
      the structure of the well-ordered N-terminal WD40 domain of Nsa1, and then SAXS
      was used to resolve the structure of the C-terminus of Nsa1 in solution. Solution
      scattering data was collected from full-length Nsa1 in solution. The theoretical
      scattering amplitudes were calculated from the high-resolution crystal structure
      of the WD40 domain, and then a combination of rigid body and ab initio modeling
      revealed the C-terminus of Nsa1. Through this hybrid approach the quaternary
      structure of the entire protein was reconstructed. The methods presented here
      should be generally applicable for the hybrid structural determination of other
      proteins composed of a mix of structured and unstructured domains.

PMID- 29364242
TI  - In Vivo Single-Molecule Tracking at the Drosophila Presynaptic Motor Nerve
      Terminal.
AB  - An increasing number of super-resolution microscopy techniques are helping to
      uncover the mechanisms that govern the nanoscale cellular world. Single-molecule
      imaging is gaining momentum as it provides exceptional access to the
      visualization of individual molecules in living cells. Here, we describe a
      technique that we developed to perform single-particle tracking photo-activated
      localization microscopy (sptPALM) in Drosophila larvae. Synaptic communication
      relies on key presynaptic proteins that act by docking, priming, and promoting
      the fusion of neurotransmitter-containing vesicles with the plasma membrane. A
      range of protein-protein and protein-lipid interactions tightly regulates these
      processes and the presynaptic proteins therefore exhibit changes in mobility
      associated with each of these key events. Investigating how mobility of these
      proteins correlates with their physiological function in an intact live animal is
      essential to understanding their precise mechanism of action. Extracting protein
      mobility with high resolution in vivo requires overcoming limitations such as
      optical transparency, accessibility, and penetration depth. We describe how
      photoconvertible fluorescent proteins tagged to the presynaptic protein Syntaxin
      1A can be visualized via slight oblique illumination and tracked at the motor
      nerve terminal or along the motor neuron axon of the third instar Drosophila
      larva.

PMID- 29364243
TI  - Automated Measurement of Cryptococcal Species Polysaccharide Capsule and Cell
      Body.
AB  - The purpose of this technique is to provide a consistent, accurate, and
      manageable process for large numbers of polysaccharide capsule measurements.
      First, a threshold image is generated based on intensity values uniquely
      calculated for each image. Then, circles are detected based on contrast between
      the object and background using the well-established Circle Hough Transformation
      (CHT) algorithm. Finally, the detected cell capsules and bodies are matched
      according to center coordinates and radius size, and data is exported to the user
      in a manageable spreadsheet. The advantages of this technique are simple but
      significant. First, because these calculations are performed by an algorithm
      rather than a human both accuracy and reliability are increased. There is no
      decline in accuracy or reliability regardless of how many samples are analyzed.
      Second, this approach establishes a potential standard operating procedure for
      the Cryptococcus field instead of the current situation where capsule measurement
      varies by lab. Third, given that manual capsule measurements are slow and
      monotonous, automation allows rapid measurements on large numbers of yeast cells
      that in turn facilitates high throughput data analysis and increasingly powerful
      statistics. The major limitations of this technique come from how the algorithm
      functions. First, the algorithm will only generate circles. While Cryptococcus
      cells and their capsules take on a circular morphology, it would be difficult to
      apply this technique to non-circular object detection. Second, due to how circles
      are detected the CHT algorithm can detect enormous pseudo-circles based on the
      outer edges of several clustered circles. However, any misrepresented cell bodies
      caught within the pseudo-circle can be easily detected and removed from the
      resulting data sets. This technique is meant for measuring the circular
      polysaccharide capsules of Cryptococcus species based on India Ink bright field
      microscopy; though it could be applied to other contrast based circular object
      measurements.

PMID- 29364244
TI  - Dissection and Explant Culture of Murine Allantois for the In Vitro Analysis of
      Allantoic Attachment.
AB  - The placenta is essential for the growth and development of mammalian embryos.
      For this reason, numerous genetic alterations and likely also environmental
      insults that disturb placenta development or function can cause early pregnancy
      loss in mice and humans. Nevertheless, simple in vitro assays to screen for
      potential effects on placenta formation are lacking. Here, we focus on modeling
      the first and critical step in placenta formation, which consists of the
      attachment of the allantois to the chorion. We describe a method to rapidly
      assess the attachment of allantoic explants on immobilized alpha4beta1 integrin,
      which serves as a chorio-mimetic substrate.This in vitro approach enables a
      qualitative evaluation of the attachment and spreading behavior of multiple
      allantois explants at different consecutive time points. The protocol may be used
      to investigate the effect of targeted mouse mutations, drugs, or various
      environmental factors that have been linked to pregnancy complications or fetal
      loss on allantois attachment ex vivo.

PMID- 29364245
TI  - Microscopy Based Methods for the Assessment of Epithelial Cell Migration During
      In Vitro Wound Healing.
AB  - Cell migration is a mandatory aspect for wound healing. Creating artificial
      wounds on research animal models often results in costly and complicated
      experimental procedures, while potentially lacking in precision. In vitro culture
      of epithelial cell lines provides a suitable platform for researching the cell
      migratory behavior in wound healing and the impact of treatments on these cells.
      The physiology of epithelial cells is often studied in non-confluent conditions;
      however, this approach may not resemble natural wound healing conditions.
      Disrupting the epithelium integrity by mechanical means generates a realistic
      model, but may impede the application of molecular techniques. Consequently,
      microscopy based techniques are optimal for studying epithelial cell migration in
      vitro. Here we detail two specific methods, the artificial wound scratch assay
      and the artificial migration front assay, that can obtain quantitative and
      qualitative data, respectively, on the migratory performance of epithelial cells.

PMID- 29364246
TI  - A Protocol for Real-time 3D Single Particle Tracking.
AB  - Real-time three-dimensional single particle tracking (RT-3D-SPT) has the
      potential to shed light on fast, 3D processes in cellular systems. Although
      various RT-3D-SPT methods have been put forward in recent years, tracking high
      speed 3D diffusing particles at low photon count rates remains a challenge.
      Moreover, RT-3D-SPT setups are generally complex and difficult to implement,
      limiting their widespread application to biological problems. This protocol
      presents a RT-3D-SPT system named 3D Dynamic Photon Localization Tracking (3D
      DyPLoT), which can track particles with high diffusive speed (up to 20 um2/s) at
      low photon count rates (down to 10 kHz). 3D-DyPLoT employs a 2D electro-optic
      deflector (2D-EOD) and a tunable acoustic gradient (TAG) lens to drive a single
      focused laser spot dynamically in 3D. Combined with an optimized position
      estimation algorithm, 3D-DyPLoT can lock onto single particles with high tracking
      speed and high localization precision. Owing to the single excitation and single
      detection path layout, 3D-DyPLoT is robust and easy to set up. This protocol
      discusses how to build 3D-DyPLoT step by step. First, the optical layout is
      described. Next, the system is calibrated and optimized by raster scanning a 190
      nm fluorescent bead with the piezoelectric nanopositioner. Finally, to
      demonstrate real-time 3D tracking ability, 110 nm fluorescent beads are tracked
      in water.

PMID- 29364247
TI  - Ex Vivo Imaging of Resident CD8 T Lymphocytes in Human Lung Tumor Slices Using
      Confocal Microscopy.
AB  - CD8 T cell are key players in the fight against cancer. In order for CD8 T cells
      to kill tumor cells they need to enter into the tumor, migrate within the tumor
      microenvironment and respond adequately to tumor antigens. The recent development
      of improved imaging approaches, such as 2-photon microscopy, and the use of
      powerful mouse tumor models have shed light on some of the mechanisms that
      regulate anti-tumor T cell activities. Whereas such systems have provided
      valuable insights, they do not always predict human responses. In human, our
      knowledge in the field mainly comes from a description of fixed tumor samples
      from human patients, as well as in vitro studies. However, in vitro models lack
      the complex three-dimensional tumor milieu and, therefore, are incomplete
      approximations of in vivo T cell activities. Fresh slices made from explanted
      tissue represent a complex multi-cellular tumor environment that can act as an
      important link between co-cultured studies and animal models. Originally set up
      in murine lymph nodes1 and previously described in a JoVE article2, this approach
      has now been transposed to human tumors to examine the dynamics of both plated3
      as well as resident T cells4. Here, a protocol for the preparation of human lung
      tumor slices, immunostaining of resident CD8 T and tumor cells, and tracking of
      CD8 T lymphocytes within the tumor microenvironment using confocal microscopy is
      described. This system is uniquely placed to screen for novel immunotherapy
      agents favoring T cell migration in tumors.

PMID- 29364248
TI  - Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an
      Endogenous Post-translational Modification Profile for Target Proteins.
AB  - It is now well-appreciated that post-translational modifications (PTMs) play an
      integral role in regulating a protein's structure and function, which may be
      essential for a given protein's role both physiologically and pathologically.
      Enrichment of PTMs is often necessary when investigating the PTM status of a
      target protein, because PTMs are often transient and relatively low in abundance.
      Many pitfalls are encountered when enriching for a PTM of a target protein, such
      as buffer incompatibility, the target protein antibody is not IP-compatible, loss
      of PTM signal, and others. The degree of difficulty is magnified when
      investigating multiple PTMs like acetylation, ubiquitination, SUMOylation 2/3,
      and tyrosine phosphorylation for a given target protein. Studying a combination
      of these PTMs may be necessary, as crosstalk between PTMs is prevalent and
      critical for protein regulation. Often, these PTMs are studied in different lysis
      buffers and with unique inhibitor compositions. To simplify the process, a unique
      denaturing lysis system was developed that effectively isolates and preserves
      these four PTMs; thus, enabling investigation of potential crosstalk in a single
      lysis system. A unique filter system was engineered to remove contaminating
      genomic DNA from the lysate, which is a problematic by-product of denaturing
      buffers. Robust affinity matrices targeting each of the four PTMs were developed
      in concert with the buffer system to maximize the enrichment and detection of the
      endogenous states of these four PTMs. This comprehensive PTM detection toolset
      streamlines the process of obtaining critical information about whether a protein
      is modified by one or more of these PTMs.

PMID- 29364249
TI  - Simultaneous Distinction of Monospecific and Mixed DFS70 Patterns During ANA
      Screening with a Novel HEp-2 ELITE/DFS70 Knockout Substrate.
AB  - Systemic autoimmune connective tissue disorders are characterized by circulating
      antinuclear antibodies (ANA). Although there are several technologies available
      for ANA screening, indirect immunofluorescence (IIF) using Human epithelial cells
      2 (HEp-2) substrate remains the primary and recommended method because of its
      superior sensitivity. HEp-2 substrates can detect a multitude of patterns
      resulting from autoantibody binding to various protein and nucleic acid
      autoantigens distributed throughout the nucleus and cytoplasm of the cells. The
      great diversity of monospecific and mixed patterns resulting from positive
      reactions on HEp-2 substrate also complicate the interpretation and accuracy of
      reporting. One specific example which received utmost attention recently is the
      dense fine speckled 70 (DFS70) pattern resulting from autoantibodies that
      specifically bind to a protein called lens epithelium derived growth factor
      (LEDGF). Lack of clear association with a specific systemic autoimmune disease
      and high prevalence in healthy populations have made accurate interpretation of
      DFS70 pattern important. Accurate distinction of DFS70 pattern from disease
      associated patterns using conventional HEp-2 substrate is challenging. Moreover,
      frequent co-occurrence of DFS70 pattern along with disease-associated patterns
      such as homogeneous, speckled, and mixed homogeneous-speckled patterns complicate
      the IIF interpretation. The goal of this paper is to demonstrate the utility of a
      novel engineered HEp-2 IIF substrate that retains all advantages of conventional
      HEp-2 substrate while simultaneously providing the ability to distinguish DFS70
      pattern with high confidence in both monospecific and mixed ANA positive
      examples. The new substrate is further able to unmask disease-associated ANA
      patterns previously concealed by DFS70 pattern.

PMID- 29364250
TI  - Flow Cytometry-based Drug Screening System for the Identification of Small
      Molecules That Promote Cellular Differentiation of Glioblastoma Stem Cells.
AB  - Glioblastoma (GBM) is the most common and most lethal primary brain tumor in
      adults, causing roughly 14,000 deaths each year in the U.S. alone. Median
      survival following diagnosis is less than 15 months with maximal surgical
      resection, radiation, and temozolomide chemotherapy. The challenges inherent in
      developing more effective GBM treatments have become increasingly clear, and
      include its unyielding invasiveness, its resistance to standard treatments, its
      genetic complexity and molecular adaptability, and subpopulations of GBM cells
      with phenotypic similarities to normal stem cells, herein referred to as
      glioblastoma stem cells (GSCs). Because GSCs are required for tumor growth and
      progression, differentiation-based therapy represents a viable treatment modality
      for these incurable neoplasms. The following protocol describes a collection of
      procedures to establish a high throughput screening platform aimed at the
      identification of small molecules that promote GSC astroglial differentiation. At
      the core of the system is a glial fibrillary acidic protein (GFAP)
      differentiation reporter-construct. The protocol contains the following general
      procedures: (1) establishing GSC differentiation reporter lines; (2)
      testing/validating the relevance of the reporter to GSC self-renewal/clonogenic
      capacity; and (3) high-capacity flow-cytometry based drug screening. The
      screening platform provides a straightforward and inexpensive approach to
      identify small molecules that promote GSCs differentiation. Furthermore,
      utilization of libraries of FDA-approved drugs holds the potential for the
      identification of agents that can be repurposed more rapidly. Also, therapies
      that promote cancer stem cell differentiation are expected to work
      synergistically with current "standard of care" therapies that have been shown to
      target and eliminate primarily more differentiated cancer cells.

PMID- 29364251
TI  - SwarmSight: Real-time Tracking of Insect Antenna Movements and Proboscis
      Extension Reflex Using a Common Preparation and Conventional Hardware.
AB  - Many scientifically and agriculturally important insects use antennae to detect
      the presence of volatile chemical compounds and extend their proboscis during
      feeding. The ability to rapidly obtain high-resolution measurements of natural
      antenna and proboscis movements and assess how they change in response to
      chemical, developmental, and genetic manipulations can aid the understanding of
      insect behavior. By extending our previous work on assessing aggregate insect
      swarm or animal group movements from natural and laboratory videos using the
      video analysis software SwarmSight, we developed a novel, free, and open-source
      software module, SwarmSight Appendage Tracking (SwarmSight.org) for frame-by
      frame tracking of insect antenna and proboscis positions from conventional web
      camera videos using conventional computers. The software processes frames about
      120 times faster than humans, performs at better than human accuracy, and, using
      30 frames per second (fps) videos, can capture antennal dynamics up to 15 Hz. The
      software was used to track the antennal response of honey bees to two odors and
      found significant mean antennal retractions away from the odor source about 1 s
      after odor presentation. We observed antenna position density heat map cluster
      formation and cluster and mean angle dependence on odor concentration.

PMID- 29364252
TI  - An In Vivo Duo-color Method for Imaging Vascular Dynamics Following Contusive
      Spinal Cord Injury.
AB  - Spinal cord injury (SCI) causes significant vascular disruption at the site of
      injury. Vascular pathology occurs immediately after SCI and continues throughout
      the acute injury phase. In fact, endothelial cells appear to be the first to die
      after a contusive SCI. The early vascular events, including increased
      permeability of the blood-spinal cord barrier (BSCB), induce vasogenic edema and
      contribute to detrimental secondary injury events caused by complex injury
      mechanisms. Targeting the vascular disruption, therefore, could be a key strategy
      to reduce secondary injury cascades that contribute to histological and
      functional impairments after SCI. Previous studies were mostly performed on
      postmortem samples and were unable to capture the dynamic changes of the vascular
      network. In this study, we have developed an in vivo duo-color two-photon imaging
      method to monitor acute vascular dynamic changes following contusive SCI. This
      approach allows detecting blood flow, vessel diameter, and other vascular
      pathologies at various sites of the same rat pre- and post-injury. Overall, this
      method provides an excellent venue for investigating vascular dynamics.

PMID- 29364253
TI  - Oral Biofilm Sampling for Microbiome Analysis in Healthy Children.
AB  - Oral biofilm and its molecular analysis provide a basis for investigating various
      dental research and clinical questions. Knowledge of biofilm composition leads to
      a better understanding of cariogenic and periopathogenic mechanisms. Microbial
      changes taking place in the oral cavity during childhood are of interest for
      several reasons. The evolution of the child oral microbiota and shifts in its
      composition need to be analyzed further to understand and possibly prevent the
      onset of disease. At the same time, advanced knowledge of the natural composition
      of oral biofilm is needed. Early stages of caries-free permanent dentition with
      healthy gums provide a widely unaffected subgingival habitat that can serve as an
      in situ baseline for studying features of oral health and disease. Analysis of
      children's oral biofilm during different stages in life is thus an important
      theme in the field. Modern molecular analysis methods can provide comprehensive
      information about the bacterial diversity of such biofilms. To enable microbiota
      data comparison, it is important to standardize each step in the procedure for
      molecular data generation. This procedure spans from clinical sampling, Next
      Generation Sequencing (NGS), bioinformatic data processing, to taxonomic
      interpretation. One of the most critical factors here is biofilm sampling.
      Sampling in children is even more challenging in particular due to limited space
      in subgingival areas. We thus focus on the use of paper points for subgingival
      sampling. This article provides a detailed protocol for oral biofilm sampling of
      the subgingival sulcus, the mucosa, and saliva in children.

PMID- 29364254
TI  - Utilizing the Modified T-Maze to Assess Functional Memory Outcomes After Cardiac
      Arrest.
AB  - BACKGROUND: Evaluating mild to moderate cognitive impairment in a global cerebral
      ischemia (i.e. cardiac arrest) model can be difficult due to poor locomotion
      after surgery. For example, rats who undergo surgical procedures and are
      subjected to the Morris water maze may not be able to swim, thus voiding the
      experiment. New Method: We established a modified behavioral spontaneous
      alternation T-maze test. The major advantage of the modified T-maze protocol is
      its relatively simple design that is powerful enough to assess functional
      learning/memory after ischemia. Additionally, the data analysis is simple and
      straightforward. We used the T-maze to determine the rats' learning/memory
      deficits both in the presence or absence of mild to moderate (6 min) asphyxial
      cardiac arrest (ACA). Rats have a natural tendency for exploration and will
      explore the alternate arms in the T-maze, whereas hippocampal-lesioned rats tend
      to adopt a side-preference resulting in decreased spontaneous alternation ratios,
      revealing the hippocampal-related functional learning/memory in the presence or
      absence of ACA. RESULTS: ACA groups have higher side-preference ratios and lower
      alternations as compared to control. Comparison with Existing Method(s): The
      Morris water and Barnes maze are more prominent for assessing learning/memory
      function. However, the Morris water maze is more stressful than other mazes. The
      Barnes maze is widely used to measure reference (long-term) memory, while ACA
      induced neurocognitive deficits are more closely related to working (short-term)
      memory. CONCLUSIONS: We have developed a simple, yet effective strategy to
      delineate working (short-term) memory via the T-maze in our global cerebral
      ischemia model (ACA).

PMID- 29364255
TI  - A Prediction Error-driven Retrieval Procedure for Destabilizing and Rewriting
      Maladaptive Reward Memories in Hazardous Drinkers.
AB  - Maladaptive reward memories (MRMs) can become unstable following retrieval under
      certain conditions, allowing their modification by subsequent new learning.
      However, robust (well-rehearsed) and chronologically old MRMs, such as those
      underlying substance use disorders, do not destabilize easily when retrieved. A
      key determinate of memory destabilization during retrieval is prediction error
      (PE). We describe a retrieval procedure for alcohol MRMs in hazardous drinkers
      that specifically aims to maximize the generation of PE and therefore the
      likelihood of MRM destabilization. The procedure requires explicitly generating
      the expectancy of alcohol consumption and then violating this expectancy
      (withholding alcohol) following the presentation of a brief set of prototypical
      alcohol cue images (retrieval + PE). Control procedures involve presenting the
      same cue images, but allow alcohol to be consumed, generating minimal PE
      (retrieval-no PE) or generate PE without retrieval of alcohol MRMs, by presenting
      orange juice cues (no retrieval + PE). Subsequently, we describe a multisensory
      disgust-based counterconditioning procedure to probe MRM destabilization by re
      writing alcohol cue-reward associations prior to reconsolidation. This procedure
      pairs alcohol cues with images invoking pathogen disgust and an extremely bitter
      tasting solution (denatonium benzoate), generating gustatory disgust. Following
      retrieval + PE, but not no retrieval + PE or retrieval-no PE, counterconditioning
      produces evidence of MRM rewriting as indexed by lasting reductions in alcohol
      cue valuation, attentional capture, and alcohol craving.

PMID- 29364256
TI  - A Protocol for Decellularizing Mouse Cochleae for Inner Ear Tissue Engineering.
AB  - In mammals, mechanosensory hair cells that facilitate hearing lack the ability to
      regenerate, which has limited treatments for hearing loss. Current regenerative
      medicine strategies have focused on transplanting stem cells or genetic
      manipulation of surrounding support cells in the inner ear to encourage
      replacement of damaged stem cells to correct hearing loss. Yet, the extracellular
      matrix (ECM) may play a vital role in inducing and maintaining function of hair
      cells, and has not been well investigated. Using the cochlear ECM as a scaffold
      to grow adult stem cells may provide unique insights into how the composition and
      architecture of the extracellular environment aids cells in sustaining hearing
      function. Here we present a method for isolating and decellularizing cochleae
      from mice to use as scaffolds accepting perfused adult stem cells. In the current
      protocol, cochleae are isolated from euthanized mice, decellularized, and
      decalcified. Afterward, human Wharton's jelly cells (hWJCs) that were isolated
      from the umbilical cord were carefully perfused into each cochlea. The cochleae
      were used as bioreactors, and cells were cultured for 30 days before undergoing
      processing for analysis. Decellularized cochleae retained identifiable
      extracellular structures, but did not reveal the presence of cells or noticeable
      fragments of DNA. Cells perfused into the cochlea invaded most of the interior
      and exterior of the cochlea and grew without incident over a duration of 30 days.
      Thus, the current method can be used to study how cochlear ECM affects cell
      development and behavior.

PMID- 29364257
TI  - Optimal Preparation of Formalin Fixed Samples for Peptide Based Matrix Assisted
      Laser Desorption/Ionization Mass Spectrometry Imaging Workflows.
AB  - The use of matrix-assisted laser desorption/ionization, mass spectrometry imaging
      (MALDI MSI) has rapidly expanded, since this technique analyzes a host of
      biomolecules from drugs and lipids to N-glycans. Although various sample
      preparation techniques exist, detecting peptides from formaldehyde preserved
      tissues remains one of the most difficult challenges for this type of mass
      spectrometric analysis. For this reason, we have created and optimized a robust
      methodology that preserves the spatial information contained within the sample,
      while eliciting the greatest number of ionizable peptides. We have also aimed to
      achieve this in a cost effective and simple way, thereby eliminating potential
      bias or preparation error, which can occur when using automated instrumentation.
      The end result is a reproducible and inexpensive protocol.

PMID- 29364258
TI  - Nanothermite with Meringue-like Morphology: From Loose Powder to Ultra-porous
      Objects.
AB  - The goal of the protocol described in this article is to prepare aluminothermic
      compositions (nanothermites) in the form of porous, monolithic objects.
      Nanothermites are combustible materials made up of inorganic fuel and an
      oxidizer. In nanothermite foams, aluminum is the fuel and aluminum phosphate and
      tungsten trioxide are the oxidizing moieties. The highest flame propagation
      velocities (FPVs) in nanothermites are observed in loose powders and FPVs are
      strongly decreased by pelletizing nanothermite powders. From a physical
      standpoint, nanothermite loose powders are metastable systems. Their properties
      can be altered by unintentional compaction induced by shocks or vibrations or by
      the segregation of particles over time by settling phenomena, which originates
      from the density differences of their components. Moving from a powder to an
      object is the challenge that must be overcome to integrate nanothermites in
      pyrotechnic systems. Nanothermite objects must have both a high open porosity and
      good mechanical strength. Nanothermite foams meet both of these criteria, and
      they are prepared by dispersing a nano-sized aluminothermic mixture (Al/WO3) in
      orthophosphoric acid. The reaction of aluminum with the acid solution gives the
      AlPO4 "cement" in which Al and WO3 nanoparticles are embedded. In nanothermite
      foams, aluminum phosphate plays the dual role of binder and oxidizer. This method
      can be used with tungsten trioxide, which is not altered by the preparation
      process. It could probably be extended to some oxides, which are commonly used
      for the preparation of high performance nanothermites. The WO3-based nanothermite
      foams described in this article are particularly insensitive to impact and
      friction, which makes them far safer to handle than loose Al/WO3 powder. The fast
      combustion of these materials has interesting applications in pyrotechnic
      igniters. Their use in detonators as primers would require the incorporation of a
      secondary explosive in their composition.

PMID- 29364259
TI  - Second Harmonic Generation Signals in Rabbit Sclera As a Tool for Evaluation of
      Therapeutic Tissue Cross-linking (TXL) for Myopia.
AB  - Methods to strengthen tissue by introducing chemical bonds (non-enzymatic cross
      linking) into structural proteins (fibrillar collagens) for therapy include
      photochemical cross-linking and tissue cross-linking (TXL) methods. Such methods
      for inducing mechanical tissue property changes are being employed to the cornea
      in corneal thinning (mechanically weakened) disorders such as keratoconus as well
      as the sclera in progressive myopia, where thinning and weakening of the
      posterior sclera occurs and likely contributes to axial elongation. The primary
      target proteins for such tissue strengthening are fibrillar collagens which
      constitute the great majority of dry weight proteins in the cornea and sclera.
      Fortuitously, fibrillar collagens are the main source of second harmonic
      generation signals in the tissue extracellular space. Therefore, modifications of
      the collagen proteins, such as those induced through cross-linking therapies,
      could potentially be detected and quantitated through the use of second harmonic
      generation microscopy (SHGM). Monitoring SHGM signals through the use of a laser
      scanning microscopy system coupled with an infrared excitation light source is an
      exciting modern imaging method that is enjoying widespread usage in the
      biomedical sciences. Thus, the present study was undertaken in order to evaluate
      the use of SHGM microscopy as a means to measure induced cross-linking effects in
      ex vivo rabbit sclera, following an injection of a chemical cross-linking agent
      into the sub-Tenon's space (sT), an injection approach that is standard practice
      for causing ocular anesthesia during ophthalmologic clinical procedures. The
      chemical cross-linking agent, sodium hydroxymethylglycinate (SMG), is from a
      class of cosmetic preservatives known as formaldehyde releasing agents (FARs).
      Scleral changes following reaction with SMG resulted in increases in SHG signals
      and correlated with shifts in thermal denaturation temperature, a standard method
      for evaluating induced tissue cross-linking effects.

PMID- 29364260
TI  - Reactive Vapor Deposition of Conjugated Polymer Films on Arbitrary Substrates.
AB  - We demonstrate a method of conformally coating conjugated polymers on arbitrary
      substrates using a custom-designed, low-pressure reaction chamber. Conductive
      polymers, poly(3,4-ethylenedioxythiophene) (PEDOT) and poly(3,4
      propylenedioxythiophene) (PProDOT), and a semiconducting polymer, poly(thieno[3,2
      b]thiophene) (PTT), were deposited on unconventional highly-disordered and
      textured substrates with high surface areas, such as paper, towels and fabrics.
      This reported deposition chamber is an improvement of previous vapor reactors
      because our system can accommodate both volatile and nonvolatile monomers, such
      as 3,4-propylenedioxythiophene and thieno[3,2-b]thiophene. Utilization of both
      solid and liquid oxidants are also demonstrated. One limitation of this method is
      that it lacks sophisticated in situ thickness monitors. Polymer coatings made by
      the commonly used solution-based coating methods, such as spin-coating and
      surface grafting, are often not uniform or susceptible to mechanical degradation.
      This reported vapor phase deposition method overcomes those drawbacks and is a
      strong alternative to common solution-based coating methods. Notably, polymer
      films coated by the reported method are uniform and conformal on rough surfaces,
      even at a micrometer scale. This feature allows for future application of vapor
      deposited polymers in electronics devices on flexible and highly textured
      substrates.

PMID- 29364261
TI  - Visualizing Leukocyte Rolling and Adhesion in Angiotensin II-Infused Mice:
      Techniques and Pitfalls.
AB  - Epifluorescence intravital video microscopy (IVM) of blood vessels is an
      established method to evaluate the activation of immune cells and their ability
      to role and adhere to the endothelial layer. Visualization of circulating cells
      by injection of fluorescent dyes or fluorophore-coupled antibodies is commonly
      used. Alternatively, fluorescent reporter mice can be used. Interactions of
      leukocytes, in particular lysozyme M+ (LysM+) monocytes, with the vessel wall
      play pivotal roles in promoting vascular dysfunction and arterial hypertension.
      We here present the technique to visualize and quantify leukocyte rolling and
      adhesion in carotid arteries in angiotensin II (AngII)-induced hypertension in
      mice by IVM. The implantation of a catheter damages the vascular wall and leads
      to altered blood cell responses. We compared different injection techniques and
      administration routes to visualize leukocytes in a LysMCre+IRG+ mouse with
      widespread expression of red fluorescent protein and conditional expression of
      green fluorescent protein in LysM+ cells. To study LysM+ cell activation, we used
      AngII infused mice in which rolling and adhesion of leukocytes to the endothelium
      is increased. We either injected acridine orange using a jugular catheter or
      directly though the tail vein and compared the amount of rolling and adhering
      cells. We found that jugular catheter implantation per se increased the number of
      rolling and adhering LysM+ cells in sham-infused LysMCre+IRG+ mice compared to
      controls. This activation was augmented in AngII-infused mice. Interestingly,
      injecting acridine orange directly through the tail vein did not increase LysM+
      cell adhesion or rolling in sham-infused mice. We thereby demonstrated the
      importance of transgenic reporter mice expressing fluorescent proteins to not
      interfere with in vivo processes during experimentation. Furthermore, tail vein
      injection of fluorescent tracers might be a possible alternative to jugular
      catheter injections.

PMID- 29364262
TI  - Utilization of Stop-flow Micro-tubing Reactors for the Development of Organic
      Transformations.
AB  - A new reaction screening technology for organic synthesis was recently
      demonstrated by combining elements from both continuous micro-flow and
      conventional batch reactors, coined stop-flow micro-tubing (SFMT) reactors. In
      SFMT, chemical reactions that require high pressure can be screened in parallel
      through a safer and convenient way. Cross-contamination, which is a common
      problem in reaction screening for continuous flow reactors, is avoided in SFMT.
      Moreover, the commercially available light-permeable micro-tubing can be
      incorporated into SFMT, serving as an excellent choice for light-mediated
      reactions due to a more effective uniform light exposure, compared to batch
      reactors. Overall, the SFMT reactor system is similar to continuous flow reactors
      and more superior than batch reactors for reactions that incorporate gas reagents
      and/or require light-illumination, which enables a simple but highly efficient
      reaction screening system. Furthermore, any successfully developed reaction in
      the SFMT reactor system can be conveniently translated to continuous-flow
      synthesis for large scale production.

PMID- 29364263
TI  - Sample Preparation and Imaging of Exosomes by Transmission Electron Microscopy.
AB  - Exosomes are nano-sized extracellular vesicles secreted by body fluids and are
      known to represent the characteristics of cells that secrete them. The contents
      and morphology of the secreted vesicles reflect cell behavior or physiological
      status, for example cell growth, migration, cleavage, and death. The exosomes'
      role may depend highly on size, and the size of exosomes varies from 30 to 300
      nm. The most widely used method for exosome imaging is negative staining, while
      other results are based on Cryo-Transmission Electron Microscopy, Scanning
      Electron Microscopy, and Atomic Force Microscopy. The typical exosome's
      morphology assessed through negative staining is a cup-shape, but further details
      are not yet clear. An exosome well-characterized through structural study is
      necessary particular in medical and pharmaceutical fields. Therefore, function
      dependent morphology should be verified by electron microscopy techniques such as
      labeling a specific protein in the detailed structure of exosome. To observe
      detailed structure, ultrathin sectioned images and negative stained images of
      exosomes were compared. In this protocol, we suggest transmission electron
      microscopy for the imaging of exosomes including negative staining, whole mount
      immuno-staining, block preparation, thin section, and immuno-gold labelling.

PMID- 29364264
TI  - Recording Synaptic Plasticity in Acute Hippocampal Slices Maintained in a Small
      volume Recycling-, Perfusion-, and Submersion-type Chamber System.
AB  - Even though experiments on brain slices have been in use since 1951, problems
      remain that reduce the probability of achieving a stable and successful analysis
      of synaptic transmission modulation when performing field potential or
      intracellular recordings. This manuscript describes methodological aspects that
      might be helpful in improving experimental conditions for the maintenance of
      acute brain slices and for recording field excitatory postsynaptic potentials in
      a commercially available submersion chamber with an outflow-carbogenation unit.
      The outflow-carbogenation helps to stabilize the oxygen level in experiments that
      rely on the recycling of a small buffer reservoir to enhance the cost-efficiency
      of drug experiments. In addition, the manuscript presents representative
      experiments that examine the effects of different carbogenation modes and
      stimulation paradigms on the activity-dependent synaptic plasticity of synaptic
      transmission.

PMID- 29364265
TI  - Endoscopic Endonasal Trans-sphenoidal Approach: Minimally Invasive Surgery for
      Pituitary Adenomas.
AB  - Endoscopic endonasal trans-sphenoidal surgery has become the gold standard for
      the surgical treatment of pituitary adenomas and many other pituitary lesions.
      Refinements in surgical techniques, technological advancements, and incorporation
      of neuronavigation have rendered this surgery minimally invasive. The
      complication rates of this surgery are very low while excellent results are
      consistently obtained through this approach. This paper focuses on the step-by
      step surgical approach to pituitary adenomas, which is based on personal
      experience, and details the results obtained with this minimally invasive
      surgery.

PMID- 29364266
TI  - Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human
      Primary NK Cells.
AB  - The efficient transduction of specific genes into natural killer (NK) cells has
      been a major challenge. Successful transductions are critical to defining the
      role of the gene of interest in the development, differentiation, and function of
      NK cells. Recent advances related to chimeric antigen receptors (CARs) in cancer
      immunotherapy accentuate the need for an efficient method to deliver exogenous
      genes to effector lymphocytes. The efficiencies of lentiviral-mediated gene
      transductions into primary human or mouse NK cells remain significantly low,
      which is a major limiting factor. Recent advances using cationic polymers, such
      as polybrene, show an improved gene transduction efficiency in T cells. However,
      these products failed to improve the transduction efficiencies of NK cells. This
      work shows that dextran, a branched glucan polysaccharide, significantly improves
      the transduction efficiency of human and mouse primary NK cells. This highly
      reproducible transduction methodology provides a competent tool for transducing
      human primary NK cells, which can vastly improve clinical gene delivery
      applications and thus NK cell-based cancer immunotherapy.

PMID- 29364267
TI  - Culturing In Vivo-like Murine Astrocytes Using the Fast, Simple, and Inexpensive
      AWESAM Protocol.
AB  - The AWESAM (a low-cost easy stellate astrocyte method) protocol entails a fast,
      simple, and inexpensive way to generate large quantities of in vivo-like mouse
      and rat astrocyte monocultures: Brain cells can be isolated from different brain
      regions, and after a week of cell culture, non-astrocytic cells are shaken off by
      placing the culture dishes on a shaker for 6 h in the incubator. The remaining
      astrocytes are then passaged into new plates with an astrocyte-specific medium
      (termed NB+H). NB+H contains low concentrations of heparin-binding EGF-like
      growth factor (HBEGF), which is used in place of serum in medium. After growing
      in NB+H, AWESAM astrocytes have a stellate morphology and feature fine processes.
      Moreover, these astrocytes have more in vivo-like gene expression than astrocytes
      generated by previously published methods. Ca2+ imaging, vesicle dynamics, and
      other events close to the membrane can thus be studied in the fine astrocytic
      processes in vitro, e.g., using live cell confocal or TIRF microscopy. Notably,
      AWESAM astrocytes also exhibit spontaneous Ca2+ signaling similar to astrocytes
      in vivo.

PMID- 29364268
TI  - Visual Evoked Potential Recordings in Mice Using a Dry Non-invasive Multi-channel
      Scalp EEG Sensor.
AB  - For scalp EEG research environments with laboratory mice, we designed a dry-type
      16 channel EEG sensor which is non-invasive, deformable, and re-usable because of
      the plunger-spring-barrel structural facet and mechanical strengths resulting
      from metal materials. The whole process for acquiring the VEP responses in vivo
      from a mouse consists of four steps: (1) sensor assembly, (2) animal preparation,
      (3) VEP measurement, and (4) signal processing. This paper presents
      representative measurements of VEP responses from multiple mice with a submicro
      voltage signal resolution and sub-hundred millisecond temporal resolution.
      Although the proposed method is safer and more convenient compared to other
      previously reported animal EEG acquiring methods, there are remaining issues
      including how to enhance the signal-to-noise ratio and how to apply this
      technique with freely moving animals. The proposed method utilizes easily
      available resources and shows a repetitive VEP response with a satisfactory
      signal quality. Therefore, this method could be utilized for longitudinal
      experimental studies and reliable translational research exploiting non-invasive
      paradigms.

PMID- 29364270
TI  - An Efficient In Vitro Transposition Method by a Transcriptionally Regulated
      Sleeping Beauty System Packaged into an Integration Defective Lentiviral Vector.
AB  - The Sleeping Beauty (SB) transposon is a non-viral integrating system with proven
      efficacy for gene transfer and functional genomics. To optimize the SB transposon
      machinery, a transcriptionally regulated hyperactive transposase (SB100X) and T2
      based transposon are employed. Typically, the transposase and transposon are
      provided transiently by plasmid transfection and SB100X expression is driven by a
      constitutive promoter. Here, we describe an efficient method to deliver the SB
      components to human cells that are resistant to several physical and chemical
      transfection methods, to control SB100X expression and stably integrate a gene of
      interest (GOI) through a "cut and paste" SB mechanism. The expression of
      hyperactive transposase is tightly controlled by the Tet-ON system, widely used
      to control gene expression since 1992. The gene of interest is flanked by
      inverted repeats (IR) of the T2 transposon. Both SB components are packaged in
      integration defective lentiviral vectors transiently produced in HEK293T cells.
      Human cells, either cell lines or primary cells from human tissue, are in vitro
      transiently transduced with viral vectors. Upon addition of doxycycline (dox,
      tetracycline analog) into the culture medium, a fine-tuning of transposase
      expression is measured and results in a long-lasting integration of the gene of
      interest in the genome of the treated cells. This method is efficient and
      applicable to the cell line (e.g., HeLa cells) and primary cells (e.g., human
      primary keratinocytes), and thus represents a valuable tool for genetic
      engineering and therapeutic gene transfer.

PMID- 29364269
TI  - Three-dimensional Tissue Engineered Aligned Astrocyte Networks to Recapitulate
      Developmental Mechanisms and Facilitate Nervous System Regeneration.
AB  - Neurotrauma and neurodegenerative disease often result in lasting neurological
      deficits due to the limited capacity of the central nervous system (CNS) to
      replace lost neurons and regenerate axonal pathways. However, during nervous
      system development, neuronal migration and axonal extension often occur along
      pathways formed by other cells, referred to as "living scaffolds". Seeking to
      emulate these mechanisms and to design a strategy that circumvents the inhibitory
      environment of the CNS, this manuscript presents a protocol to fabricate tissue
      engineered astrocyte-based "living scaffolds". To create these constructs, we
      employed a novel biomaterial encasement scheme to induce astrocytes to self
      assemble into dense three-dimensional bundles of bipolar longitudinally-aligned
      somata and processes. First, hollow hydrogel micro-columns were assembled, and
      the inner lumen was coated with collagen extracellular-matrix. Dissociated
      cerebral cortical astrocytes were then delivered into the lumen of the
      cylindrical micro-column and, at a critical inner diameter of <350 um,
      spontaneously self-aligned and contracted to produce long fiber-like cables
      consisting of dense bundles of astrocyte processes and collagen fibrils measuring
      <150 um in diameter yet extending several cm in length. These engineered living
      scaffolds exhibited >97% cell viability and were virtually exclusively comprised
      of astrocytes expressing a combination of the intermediate filament proteins
      glial-fibrillary acidic protein (GFAP), vimentin, and nestin. These aligned
      astrocyte networks were found to provide a permissive substrate for neuronal
      attachment and aligned neurite extension. Moreover, these constructs maintain
      integrity and alignment when extracted from the hydrogel encasement, making them
      suitable for CNS implantation. These preformed constructs structurally emulate
      key cytoarchitectural elements of naturally occurring glial-based "living
      scaffolds" in vivo. As such, these engineered living scaffolds may serve as test
      beds to study neurodevelopmental mechanisms in vitro or facilitate
      neuroregeneration by directing neuronal migration and/or axonal pathfinding
      following CNS degeneration in vivo.

PMID- 29364271
TI  - Detecting Estrogenic Ligands in Personal Care Products using a Yeast Estrogen
      Screen Optimized for the Undergraduate Teaching Laboratory.
AB  - The Yeast Estrogen Screen (YES) is used to detect estrogenic ligands in
      environmental samples and has been broadly applied in studies of endocrine
      disruption. Estrogenic ligands include both natural and manmade "Environmental
      Estrogens" (EEs) found in many consumer goods including Personal Care Products
      (PCPs), plastics, pesticides, and foods. EEs disrupt hormone signaling in humans
      and other animals, potentially reducing fertility and increasing disease risk.
      Despite the importance of EEs and other Endocrine Disrupting Chemicals (EDCs) to
      public health, endocrine disruption is not typically included in undergraduate
      curricula. This shortcoming is partly due to a lack of relevant laboratory
      activities that illustrate the principles involved while also being accessible to
      undergraduate students. This article presents an optimized YES for quantifying
      ligands in personal care products that bind estrogen receptors alpha (ERalpha)
      and/or beta (ERbeta). The method incorporates one of the two colorimetric
      substrates (ortho-nitrophenyl-beta-D-galactopyranoside (ONPG) or chlorophenol red
      beta-D-galactopyranoside (CPRG)) that are cleaved by beta-galactosidase, a 6-day
      refrigerated incubation step to facilitate use in undergraduate laboratory
      courses, an automated application for LacZ calculations, and R code for the
      associated 4-parameter logistic regression analysis. The protocol has been
      designed to allow undergraduate students to develop and conduct experiments in
      which they screen products of their choosing for estrogen mimics. In the process,
      they learn about endocrine disruption, cell culture, receptor binding, enzyme
      activity, genetic engineering, statistics, and experimental design.
      Simultaneously, they also practice fundamental and broadly applicable laboratory
      skills, such as: calculating concentrations; making solutions; demonstrating
      sterile technique; serially diluting standards; constructing and interpolating
      standard curves; identifying variables and controls; collecting, organizing, and
      analyzing data; constructing and interpreting graphs; and using common laboratory
      equipment such as micropipettors and spectrophotometers. Thus, implementing this
      assay encourages students to engage in inquiry-based learning while exploring
      emerging issues in environmental science and health.

PMID- 29364272
TI  - Frame-by-Frame Video Analysis of Idiosyncratic Reach-to-Grasp Movements in
      Humans.
AB  - Prehension, the act of reaching to grasp an object, is central to the human
      experience. We use it to feed ourselves, groom ourselves, and manipulate objects
      and tools in our environment. Such behaviors are impaired by many sensorimotor
      disorders, yet our current understanding of their neural control is far from
      complete. Current technologies for investigating human reach-to-grasp movements
      often utilize motion tracking systems that can be expensive, require the
      attachment of markers or sensors to the hands, impede natural movement and
      sensory feedback, and provide kinematic output that can be difficult to
      interpret. While generally effective for studying the stereotypical reach-to
      grasp movements of healthy sighted adults, many of these technologies face
      additional limitations when attempting to study the unpredictable and
      idiosyncratic reach-to-grasp movements of young infants, unsighted adults, and
      patients with neurological disorders. Thus, we present a novel, inexpensive, and
      highly reliable yet flexible protocol for quantifying the temporal and kinematic
      structure of idiosyncratic reach-to-grasp movements in humans. High speed video
      cameras capture multiple views of the reach-to-grasp movement. Frame-by-frame
      video analysis is then used to document the timing and magnitude of pre-defined
      behavioral events such as movement start, collection, maximum height, peak
      aperture, first contact, and final grasp. The temporal structure of the movement
      is reconstructed by documenting the relative frame number of each event while the
      kinematic structure of the hand is quantified using the ruler or measure function
      in photo editing software to calibrate 2 dimensional linear distances between two
      body parts or between a body part and the target. Frame-by-frame video analysis
      can provide a quantitative and comprehensive description of idiosyncratic reach
      to-grasp movements and will enable researchers to expand their area of
      investigation to include a greater range of naturalistic prehensile behaviors,
      guided by a wider variety of sensory modalities, in both healthy and clinical
      populations.

PMID- 29364273
TI  - A Morphometric and Cellular Analysis Method for the Murine Mandibular Condyle.
AB  - The temporomandibular joint (TMJ) has the capacity to adapt to external stimuli,
      and loading changes can affect the position of condyles, as well as the
      structural and cellular components of the mandibular condylar cartilage (MCC).
      This manuscript describes methods for analyzing these changes and a method for
      altering the loading of the TMJ in mice (i.e., compressive static TMJ loading).
      The structural evaluation illustrated here is a simple morphometric approach that
      uses the Digimizer software and is performed in radiographs of small bones. In
      addition, the analysis of cellular changes leading to alterations in collagen
      expression, bone remodeling, cell division, and proteoglycan distribution in the
      MCC is described. The quantification of these changes in histological sections -
      by counting the positive fluorescent pixels using image software and measuring
      the distance mapping and stained area with Digimizer - is also demonstrated. The
      methods shown here are not limited to the murine TMJ, but could be used on
      additional bones of small experimental animals and in other regions of
      endochondral ossification.

PMID- 29364274
TI  - Observation and Analysis of Blinking Surface-enhanced Raman Scattering.
AB  - From a single molecule at a silver nanoaggregate junction, blinking surface
      enhanced Raman scattering (SERS) is observed. Here, a protocol is presented on
      how to prepare the SERS-active silver nanoaggregate, record a video of certain
      blinking spots in the microscopic image, and analyze the blinking statistics. In
      this analysis, a power law reproduces the probability distributions for bright
      events relative to their duration. The probability distributions for dark events
      are fitted by a power law with an exponential function. The parameters of the
      power law represent molecular behavior in both bright and dark states. The random
      walk model and the speed of the molecule across the entire silver surface can be
      estimated. It is difficult to estimate even when using averages, autocorrelation
      functions, and super-resolution SERS imaging. In the future, power law analyses
      should be combined with spectral imaging, because the origins of blinking cannot
      be confirmed by this analysis method alone.

PMID- 29364275
TI  - Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant
      Calreticulin in Cytokine Dependent Hematopoietic Cells.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) is an adaptive
      immunity system in prokaryotes that has been repurposed by scientists to generate
      RNA-guided nucleases, such as CRISPR-associated (Cas) 9 for site-specific
      eukaryotic genome editing. Genome engineering by Cas9 is used to efficiently,
      easily and robustly modify endogenous genes in many biomedically-relevant
      mammalian cell lines and organisms. Here we show an example of how to utilize the
      CRISPR/Cas9 methodology to understand the biological function of specific genetic
      mutations. We model calreticulin (CALR) mutations in murine interleukin-3 (mIL-3)
      dependent pro-B (Ba/F3) cells by delivery of single guide RNAs (sgRNAs) targeting
      the endogenous Calr locus in the specific region where insertion and/or deletion
      (indel) CALR mutations occur in patients with myeloproliferative neoplasms (MPN),
      a type of blood cancer. The sgRNAs create double strand breaks (DSBs) in the
      targeted region that are repaired by non-homologous end joining (NHEJ) to give
      indels of various sizes. We then employ the standard Ba/F3 cellular
      transformation assay to understand the effect of physiological level expression
      of Calr mutations on hematopoietic cellular transformation. This approach can be
      applied to other genes to study their biological function in various mammalian
      cell lines.

PMID- 29364276
TI  - A Rat Model of Mild Intrauterine Hypoperfusion with Microcoil Stenosis.
AB  - Intrauterine hypoperfusion/ischemia is one of the major causes of
      intrauterine/fetal growth restriction, preterm birth, and low birth weight. Most
      studies of this phenomenon have been performed in either models with severe
      intrauterine ischemia or models with gradient degree of intrauterine
      hypoperfusion. No study has been performed in a model on uniform mild
      intrauterine hypoperfusion (MIUH). Two models have been used for studies of MIUH:
      a model based on suture ligation of either side of the arterial arcade formed
      with the uterine and ovarian arteries, and a transient model based on clipping
      the bilateral ovarian arteries and aorta having patency. Those two rodent models
      of MIUH have some limitations, e.g., not all fetuses are subjected to MIUH,
      depending on their position in the uterine horn. In our MIUH model, all fetuses
      are subjected to a comparable level of intrauterine hypoperfusion. MIUH was
      achieved by mild stenosis of all four arteries feeding the uterus, i.e., the
      bilateral uterine and ovarian arteries. Arterial stenosis was induced by metal
      microcoils wrapped around the feeding arteries. Producing arterial stenosis with
      microcoils allowed us to control, optimize, and reproduce decreased blood flow
      with very little inter-animal variability and a low mortality rate, thus enabling
      accurate evaluation. When microcoils with an inner diameter of 0.24 mm were used,
      the blood flow in both the placenta and fetus was mildly decreased (approximately
      30% from the pre-stenosis level in the placenta). The offspring of our MIUH model
      clearly demonstrates long-lasting alterations in neurological, neuroanatomical
      and behavioral test results.

PMID- 29364277
TI  - Synthesis of Functionalized 10-nm Polymer-coated Gold Particles for Endothelium
      Targeting and Drug Delivery.
AB  - Gold nanoparticles (AuNPs) have been used extensively in medical research due to
      their size, biocompatibility, and modifiable surface. Specific targeting and drug
      delivery are some of the applications of these AuNPs, but endothelial
      extracellular matrices' defensive properties hamper particle uptake. To address
      this issue, we describe a synthesis method for ultrasmall gold nanoparticles to
      improve vascular delivery, with customizable functional groups and polymer
      lengths for further adjustments. The protocol yields 2.5 nm AuNPs that are capped
      with tetrakis(hydroxymethyl)phosphonium chloride (THPC). The replacement of THPC
      with hetero-functional polyethylene glycol (PEG) on the surface of the AuNP
      increases the hydrodynamic radius to 10.5 nm while providing various functional
      groups on the surface. The last part of the protocol includes an optional
      addition of a fluorophore to allow the AuNPs to be visualized under fluorescence
      to track nanoparticle uptake. Dialysis and lyophilization were used to purify and
      isolate the AuNPs. These fluorescent nanoparticles can be visualized in both in
      vitro and in vivo experiments due to the biocompatible PEG coating and
      fluorescent probes. Additionally, the size range of these nanoparticles render
      them an ideal candidate for probing the glycocalyx without disrupting normal
      vasculature function, which may lead to improved delivery and therapeutics.

PMID- 29364278
TI  - Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and
      Osteoclast Progenitors from Mice.
AB  - Bone marrow stromal cells (BMSCs) constitute a cell population routinely used as
      a representation of mesenchymal stem cells in vitro. They reside within the bone
      marrow cavity alongside hematopoietic stem cells (HSCs), which can give rise to
      red blood cells, immune progenitors, and osteoclasts. Thus, extractions of cell
      populations from the bone marrow results in a very heterogeneous mix of various
      cell populations, which can present challenges in experimental design and
      confound data interpretation. Several isolation and culture techniques have been
      developed in laboratories in order to obtain more or less homogeneous populations
      of BMSCs and HSCs invitro. Here, we present two methods for isolation of BMSCs
      and HSCs from mouse long bones: one method that yields a mixed population of
      BMSCs and HSCs and one method that attempts to separate the two cell populations
      based on adherence. Both methods provide cells suitable for osteogenic and
      adipogenic differentiation experiments as well as functional assays.

PMID- 29364279
TI  - Visualizing Intracellular SNARE Trafficking by Fluorescence Lifetime Imaging
      Microscopy.
AB  - Soluble N-ethylmaleimide sensitive fusion protein (NSF) attachment protein
      receptor (SNARE) proteins are key for membrane trafficking, as they catalyze
      membrane fusion within eukaryotic cells. The SNARE protein family consists of
      about 36 different members. Specific intracellular transport routes are catalyzed
      by specific sets of 3 or 4 SNARE proteins that thereby contribute to the
      specificity and fidelity of membrane trafficking. However, studying the precise
      function of SNARE proteins is technically challenging, because SNAREs are highly
      abundant and functionally redundant, with most SNAREs having multiple and
      overlapping functions. In this protocol, a new method for the visualization of
      SNARE complex formation in live cells is described. This method is based on
      expressing SNARE proteins C-terminally fused to fluorescent proteins and
      measuring their interaction by Forster resonance energy transfer (FRET) employing
      fluorescence lifetime imaging microscopy (FLIM). By fitting the fluorescence
      lifetime histograms with a multicomponent decay model, FRET-FLIM allows (semi
      )quantitative estimation of the fraction of the SNARE complex formation at
      different vesicles. This protocol has been successfully applied to visualize
      SNARE complex formation at the plasma membrane and at endosomal compartments in
      mammalian cell lines and primary immune cells, and can be readily extended to
      study SNARE functions at other organelles in animal, plant, and fungal cells.

PMID- 29364280
TI  - Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose
      Tolerance Test (OGTT) and Insulin Tolerance Test (ITT).
AB  - Obesity represents the most important single risk factor in the pathogenesis of
      type 2 diabetes, a disease which is characterized by a resistance to insulin
      stimulated glucose uptake and a gross decompensation of systemic glucose
      metabolism. Despite considerable progress in the understanding of glucose
      metabolism, the molecular mechanisms of its regulation in health and disease
      remain under-investigated, while novel approaches to prevent and treat diabetes
      are urgently needed. Diet derived glucose stimulates the pancreatic secretion of
      insulin, which serves as the principal regulator of cellular anabolic processes
      during the fed-state and thus balances blood glucose levels to maintain systemic
      energy status. Chronic overfeeding triggers meta-inflammation, which leads to
      alterations in peripheral insulin receptor-associated signaling and thus reduces
      the sensitivity to insulin-mediated glucose disposal. These events ultimately
      result in elevated fasting glucose and insulin levels as well as a reduction in
      glucose tolerance, which in turn serve as important indicators of insulin
      resistance. Here, we present a protocol for the generation and metabolic
      characterization of high-fat diet (HFD)-fed mice as a frequently used model of
      diet-induced insulin resistance. We illustrate in detail the oral glucose
      tolerance test (OGTT), which monitors the peripheral disposal of an orally
      administered glucose load and insulin secretion over time. Additionally, we
      present a protocol for the insulin tolerance test (ITT) to monitor whole-body
      insulin action. Together, these methods and their downstream applications
      represent powerful tools to characterize the general metabolic phenotype of mice
      as well as to specifically assess alterations in glucose metabolism. They may be
      especially useful in the broad research field of insulin resistance, diabetes and
      obesity to provide a better understanding of pathogenesis as well as to test the
      effects of therapeutic interventions.

PMID- 29364281
TI  - A Simple and Low-cost Assay for Measuring Ambulation in Mouse Models of Muscular
      Dystrophy.
AB  - Measuring functional outcomes in the treatment of muscular dystrophy is an
      essential aspect of preclinical testing. The assessment of voluntary ambulation
      in mouse models is a non-invasive and reproducible activity assay that is
      directly analogous to measures of patient ambulation such as the 6-minute walk
      test and related mobility scores. Many common methods for testing mouse
      ambulation speed and distance are based on the open field test, where an animal's
      free movement within an arena is measured over time. One major downside to this
      approach is that commercial software and equipment for high-resolution motion
      tracking is expensive and may require transferring mice to specialized facilities
      for testing. Here, we describe a low-cost, video-based system for measuring mouse
      ambulation that utilizes free and open-source software. Using this protocol, we
      demonstrate that voluntary ambulation in the dystrophin-null mdx mouse model for
      Duchenne muscular dystrophy (DMD) is decreased relative to wild-type mouse
      activity. In mdx mice expressing the utrophin transgene, these activity deficits
      are not observed and the total distance traveled is indistinguishable from wild
      type mice. This method is effective for measuring changes in voluntary ambulation
      associated with dystrophic pathology, and provides a versatile platform that can
      be readily adapted to diverse research settings.

PMID- 29364282
TI  - Phloem Sap Sampling from Brassica napus for 3D-PAGE of Protein and
      Ribonucleoprotein Complexes.
AB  - Sampling the phloem of higher plants is often laborious and significantly
      dependent on the plant species. However, proteome studies under denaturing
      conditions could be achieved in different plant species. Native protein:protein
      and protein:nucleic acid complexes from phloem samples have as yet scarcely been
      analyzed, although they might play important roles in maintenance of this
      specialized compartment or in long-distance signaling. Large molecular assemblies
      can be isolated using a blue native gel electrophoresis (BN-PAGE). Their protein
      components can be separated by a subsequent sodium dodecyl sulfate PAGE (SDS
      PAGE). However, proteins with similar molecular weights co-migrate, what can
      hinder protein identification by mass spectrometry. Combining BN-PAGE with two
      different denaturing gel electrophoresis steps, namely Tris-Tricine-urea and SDS
      PAGE, enables the additional separation of proteins according to their
      hydrophilicity/hydrophobicity and thus increases resolution and the success of
      protein identification. It even allows distinguishing proteins that only differ
      in their posttranslational modifications. In addition, blue native northern
      blotting can be applied to identify the RNA components in macromolecular
      complexes. We show that our protocol is suitable to unravel the protein and RNA
      components of native protein:protein and ribonucleoprotein (RNP) complexes
      occurring in phloem samples. Combining a blue native PAGE with two different
      denaturing PAGE steps can help to separate different kinds of large protein
      complexes, and also enables an increased identification rate of their components
      by mass spectrometry. Furthermore, the protocol is robust enough to
      simultaneously detect potentially bound nucleic acids within single protein
      complexes.

PMID- 29364283
TI  - A Simple Cell-based Immunofluorescence Assay to Detect Autoantibody Against the N
      Methyl-D-Aspartate (NMDA) Receptor in Blood.
AB  - The presence of anti-NMDA receptor autoantibody can cause various
      neuropsychiatric symptoms in the affected patients, termed anti-NMDA receptor
      autoimmune encephalitis. Detection of the specific autoantibody against the NMDA
      receptor in the blood or cerebrospinal fluid (CSF) is essential for the accurate
      diagnosis of this condition. The NMDA receptor is an ion channel protein complex
      that contains four subunits, including two mandatory NMDA receptor subunit 1
      (NR1) and one or two NMDA receptor subunit 2A (NR2A), NMDA receptor subunit 2B
      (NR2B), NMDA receptor subunit 2C (NR2C), or NMDA receptor subunit 2D (NR2D). The
      epitope of anti-NMDA receptor autoantibody was reported to be present at the
      extracellular N-terminal domain of the NR1 subunit of the NMDA receptor. The goal
      of this study is to develop a simple cell-based immunofluorescence assay that can
      be used as a screening test to detect the presence of autoantibodies against NR1
      subunit of the NMDA receptor in the blood to facilitate the clinical and basic
      research of anti-NMDA receptor autoimmune encephalitis.

PMID- 29364284
TI  - Guidelines and Experience Using Imaging Biomarker Explorer (IBEX) for Radiomics.
AB  - Imaging Biomarker Explorer (IBEX) is an open-source tool for medical imaging
      radiomics work. The purpose of this paper is to describe how to use IBEX's
      graphical user interface (GUI) and to demonstrate how IBEX calculated features
      have been used in clinical studies. IBEX allows for the import of DICOM images
      with DICOM radiation therapy structure files or Pinnacle files. Once the images
      are imported, IBEX has tools within the Data Selection GUI to manipulate the
      viewing of the images, measure voxel values and distances, and create and edit
      contours. IBEX comes with 27 preprocessing and 132 feature choices to design
      feature sets. Each preprocessing and feature category has parameters that can be
      altered. The output from IBEX is a spreadsheet that contains: 1) each feature
      from the feature set calculated for each contour in a data set, 2) image
      information about each contour in a data set, and 3) a summary of the
      preprocessing and features used with their selected parameters. Features
      calculated from IBEX have been used in studies to test the variability of
      features under different imaging conditions and in survival models to improve
      current clinical models.

PMID- 29364285
TI  - From haematopoietic stem cells to complex differentiation landscapes.
AB  - The development of mature blood cells from haematopoietic stem cells has long
      served as a model for stem-cell research, with the haematopoietic differentiation
      tree being widely used as a model for the maintenance of hierarchically organized
      tissues. Recent results and new technologies have challenged the demarcations
      between stem and progenitor cell populations, the timing of cell-fate choices and
      the contribution of stem and multipotent progenitor cells to the maintenance of
      steady-state blood production. These evolving views of haematopoiesis have broad
      implications for our understanding of the functions of adult stem cells, as well
      as the development of new therapies for malignant and non-malignant
      haematopoietic diseases.

PMID- 29364289
TI  - Methylated chromenoquinoline dyes: synthesis, optical properties, and application
      for mitochondrial labeling.
AB  - Methylated chromenoquinoline dyes were designed and synthesized, and their
      photophysical properties were investigated. These new fluorescent dyes exhibited
      relatively high quantum yields, long wavelength emissions, large Stokes shifts,
      large absorption extinction coefficients and good water-solubility. Importantly,
      these methylated cation dyes showed a specific staining ability for mitochondria
      in living cells with low cytotoxicity.

PMID- 29364286
TI  - Skin microbiota-host interactions.
AB  - The skin is a complex and dynamic ecosystem that is inhabited by bacteria,
      archaea, fungi and viruses. These microbes-collectively referred to as the skin
      microbiota-are fundamental to skin physiology and immunity. Interactions between
      skin microbes and the host can fall anywhere along the continuum between
      mutualism and pathogenicity. In this Review, we highlight how host-microbe
      interactions depend heavily on context, including the state of immune activation,
      host genetic predisposition, barrier status, microbe localization, and microbe
      microbe interactions. We focus on how context shapes the complex dialogue between
      skin microbes and the host, and the consequences of this dialogue for health and
      disease.

PMID- 29364290
TI  - A single-molecule ELISA device utilizing nanofluidics.
AB  - Single molecule analysis is desired in many areas that require the analysis of
      ultra-small volume and/or extremely low concentration samples (e.g., single-cell
      biology, medicine diagnosis, virus detection, etc.). Due to the ultra-small
      volume or concentration, the sample contains only single or countable analyte
      molecules. Thus, specific single molecules should be precisely processed and
      detected for analysis. However, except nucleic acids, most molecules are
      difficult to amplify, and a new analytical methodology for specific single
      molecules is thus essential. For this, efficient chemical processing and
      detection, which are important analytical elements, should be developed. Here, we
      report a single-molecule ELISA (enzyme-linked immunosorbent assay) device
      utilizing micro/nanofluidic technology. Both chemical processing and detection
      were integrated into an ultra-small space (102 nm in size), and the integration
      allowed precise processing (~100% capture) and detection of a specific single
      molecule (protein) for the first time. This new concept and enabling technology
      represent a significant innovation in analytical chemistry and will have a large
      impact on general biology and medicine.

PMID- 29364287
TI  - The biology and management of non-small cell lung cancer.
AB  - Important advancements in the treatment of non-small cell lung cancer (NSCLC)
      have been achieved over the past two decades, increasing our understanding of the
      disease biology and mechanisms of tumour progression, and advancing early
      detection and multimodal care. The use of small molecule tyrosine kinase
      inhibitors and immunotherapy has led to unprecedented survival benefits in
      selected patients. However, the overall cure and survival rates for NSCLC remain
      low, particularly in metastatic disease. Therefore, continued research into new
      drugs and combination therapies is required to expand the clinical benefit to a
      broader patient population and to improve outcomes in NSCLC.

PMID- 29364288
TI  - The rise of three-dimensional human brain cultures.
AB  - Pluripotent stem cells show a remarkable ability to self-organize and
      differentiate in vitro in three-dimensional aggregates, known as organoids or
      organ spheroids, and to recapitulate aspects of human brain development and
      function. Region-specific 3D brain cultures can be derived from any individual
      and assembled to model complex cell-cell interactions and to generate circuits in
      human brain assembloids. Here I discuss how this approach can be used to
      understand unique features of the human brain and to gain insights into
      neuropsychiatric disorders. In addition, I consider the challenges faced by
      researchers in further improving and developing methods to probe and manipulate
      patient-derived 3D brain cultures.

PMID- 29364291
TI  - An oxidative cross-coupling reaction of 4-hydroxydithiocoumarin and amines/thiols
      using a combination of I2 and TBHP: access to lead molecules for biomedical
      applications.
AB  - A metal-free I2/TBHP induced highly atom economic and operationally simple
      oxidative cross-coupling reaction has been developed for the direct synthesis of
      sulfenamides/sulfanes/disulfides from the reaction of 4-hydroxydithiocoumarin and
      amines/thiols. The novelties of the present protocol are unprecedented S-C bond
      formation in addition to S-N and S-S bonds, shorter reaction time, mild and
      environmentally benign reaction conditions, functional group tolerance and
      moderate to excellent yields. Moreover, the four newly synthesized compounds
      namely 4q, 6d, 6e and 7a exhibit anti-proliferative activity against the breast
      cancer cell line MCF7, and may be lead molecules for future drug development.

PMID- 29364292
TI  - Chemical-bond effect on epitaxial strain in perovskite sodium niobate.
AB  - Epitaxial films and heterostructures of perovskite oxides attract tremendous
      scientific interest because of the unique phenomena therein. Especially important
      is the epitaxial growth of films subjected to substrate-induced misfit strain. We
      show here that in contrast to conventional misfit-controlled epitaxy, chemical
      bonds determine the crystal stability and strain in epitaxial films of sodium
      niobate on different cubic substrates. Strain relaxation in sodium niobate is
      independent of misfit magnitude and proceeds through perovskite-specific tilting
      of oxygen octahedra in addition to common defect formation. The observed
      structural relaxation evidences a major role of a large internal strain that
      originates from chemical bonds in the perovskite cell. The effect of chemical
      bonds on film strain is anticipated to also control the epitaxy of other
      perovskite oxides and related compounds.

PMID- 29364293
TI  - Zr2Si: an antiferromagnetic Dirac MXene.
AB  - MXenes, which constitute a kind of graphene-like material, have been intensively
      investigated due to their applications in future nanoelectronics technology.
      These MXenes are either metallic or semiconducting, whereas Dirac cones similar
      to graphene have rarely been reported. Using first-principles calculations, we
      proposed a new MXene, namely Zr2Si, whose antiferromagnetic (AFM) ground state
      exhibited in these calculations anisotropic Dirac cones with Fermi velocities
      comparable to that in graphene. The Dirac spectrum here was determined to arise
      mainly from the dx2-y2 and dz2 orbitals of Zr atoms. Additionally, the Dirac
      cones can be gapped when taking the spin-orbit coupling (SOC) and Coulomb
      repulsive interaction (U) into account, which opens an avenue for using the Zr2Si
      MXene for electronics applications.

PMID- 29364294
TI  - Size dependence of magneto-optical activity in silver nanoparticles with
      dimensions between 10 and 60 nm studied by MCD spectroscopy.
AB  - Size-dependent magneto-optical activity in Ag nanoparticles with dimensions from
      10 to 60 nm is demonstrated with magnetic circular dichroism (MCD) spectroscopy.
      The Ag nanoparticles are prepared on the basis of a seeded-growth strategy using
      sodium citrate and/or tannic acid as reducing agents in aqueous solution. The
      obtained nanoparticles are roughly spherical, but those larger than ~28 nm have a
      slight diversity of shapes with quasi-spherical polyhedrons. They exhibit a
      derivative-like MCD response in the localized surface plasmon resonance (LSPR)
      region, which originates from two circular modes of surface magnetoplasmons. With
      an increase in the nanoparticle diameter, the bisignated MCD signal is strongly
      distorted and weakened. Such a distortion for large-sized Ag nanoparticles can be
      phenomenologically simulated on the basis of both spectral inhomogeneity and MCD
      signal lobe asymmetry. Then the maximum value of MCD amplitude (MCDmax), which is
      obtained by normalization of the amplitude to the LSPR peak absorbance, first
      increases with increasing particle diameter and then decreases with a maximum for
      the 23 nm nanoparticle. Interestingly, the MCDmax values are inversely correlated
      with the spectral bandwidth of LSPR extinction. This behaviour is discussed from
      a viewpoint of inhomogeneous effects of both spectral and size/shape
      distributions. We believe the present results will advance the design and
      application of optical devices based on magnetoplasmonics.

PMID- 29364295
TI  - Ab initio calculations and kinetic modeling of thermal conversion of methyl
      chloride: implications for gasification of biomass.
AB  - Limitations in current hot gas cleaning methods for chlorine species from biomass
      gasification may be a challenge for end use such as gas turbines, engines, and
      fuel cells, all requiring very low levels of chlorine. During devolatilization of
      biomass, chlorine is released partly as methyl chloride. In the present work, the
      thermal conversion of CH3Cl under gasification conditions was investigated. A
      detailed chemical kinetic model for pyrolysis and oxidation of methyl chloride
      was developed and validated against selected experimental data from the
      literature. Key reactions of CH2Cl with O2 and C2H4 for which data are scarce
      were studied by ab initio methods. The model was used to analyze the fate of
      methyl chloride in gasification processes. The results indicate that CH3Cl
      emissions will be negligible for most gasification technologies, but could be a
      concern for fluidized bed gasifiers, in particular in low-temperature
      gasification. The present work illustrates how ab initio theory and chemical
      kinetic modeling can help to resolve emission issues for thermal processes in
      industrial scale.

PMID- 29364296
TI  - Formation, growth and applications of femtoliter droplets on a microlens.
AB  - Formation and growth of femtoliter droplets on surface microstructures are
      important in many fundamental and practical interfacial processes, such as water
      collection, vapour condensation in cooling devices, drop self-removal on anti
      icing surfaces and fabrication of droplet-templated functional microstructures.
      In this work, we experimentally and theoretically investigate the growth of
      femtoliter oil-like liquid on the microlens surrounded by a hydrophilic planar
      area. The droplets were produced by solvent exchange, a process where the
      droplets nucleate and grow from an oversaturation created by displacing a good
      solvent by a poor solvent of the droplet liquid. Our results showed that the
      droplet fully coats the lens surface and the contact angle of the droplet
      relative to the flat surface is finely tuned over a large range by the droplet
      volume. The growth of the droplet on a microlens is largely described by the
      constant contact radius model. To demonstrate the new opportunities provided by
      the controlled formation of the droplet situated on a microlens, we will show a
      simple and effective approach for production of arrays of composite microlenses
      consisting of two types of polymers with different refractive indices. A high
      curvature of the composite microlens results in desirable diffraction patterns
      with potential application for enhanced light harvesting. Moreover, we
      demonstrate that extraction of traces of a hydrophobic solute from the flow is
      much faster as the droplet is lifted up from the channel wall by the microlens,
      promising a time effective in situ detection process in narrow channels.

PMID- 29364297
TI  - Effect of Al content on the strength of terminal silanol species in ZSM-5 zeolite
      catalysts: a quantitative DRIFTS study without the use of molar extinction
      coefficients.
AB  - The strength of terminal hydroxyl Si-OH groups (silanols) in zeolites is
      important for many non-size-selective catalytic reactions occurring onto the
      external surface of the zeolite crystals and may often be responsible for
      catalyst deactivation, e.g., coke formation. A quantitative analysis of Si-OH
      strength and its link with the Al content, hence varying silica-to-alumina ratio
      (SAR = SiO2/Al2O3), has not been established yet. Various hypotheses have been
      proposed in the literature; nonetheless, the role of Al content in determining
      silanol strength remains still unclear and the object of speculation. In this
      work, we have systematically investigated the effect of the Al content on the
      strength of terminal silanol sites in ZSM-5 zeolite catalysts with varying SAR
      using Diffuse Reflectance Infrared Fourier Transform Spectroscopy (DRIFTS) at
      variable temperatures without molar extinction coefficients. Two base probe
      molecules with different proton affinity values, pyridine and collidine, were
      used. To quantify the strength of terminal silanol sites the change of the
      terminal silanol peak in the OH stretching region, together with data on
      elemental analysis, was used. With this experimental protocol, unlike most IR
      studies, the use of molar extinction coefficients, often difficult to obtain, is
      not needed for quantification. The results reported here show for the first time
      that for ZSM-5 zeolite catalysts the fraction of occupied terminal silanol acid
      sites for both pyridine and collidine increases with increasing concentration of
      external Bronsted acid sites, hence establishing a clear link between the two
      types of acid sites. In summary, this work shows that the use of DRIFTS without
      molar extinction coefficients is able to quantitatively probe the strength of
      terminal silanol acid sites and establishes a link between the external Bronsted
      Al content and the strength of terminal silanol species in ZSM-5 zeolites with
      varying SAR at elevated temperatures.

PMID- 29364298
TI  - Synthesis of unsymmetrical benzotrichalcogenophenes by N-heterocyclic carbene
      palladium-catalyzed intramolecular direct C3-arylation of chalcogenophenes.
AB  - A series of new unsymmetrical benzotrichalcogenophenes (BTCs) were synthesized by
      the Pd-N-heterocyclic carbene catalyzed intramolecular C3-arylation of furan,
      thiophene, selenophene and tellurophene units. This is the first time that a C3
      direct arylation of selenophene and tellurophene moieties has ever been
      demonstrated.

PMID- 29364299
TI  - Toward a rational photocatalyst design: a new formation strategy of co
      catalyst/semiconductor heterostructures via in situ exsolution.
AB  - A new "post-growth" approach to implant metal sulfide nanodots (<5 nm) with high
      population and uniform dispersion into a semiconductor parent matrix was
      reported. The encapsulation modality of nanodot co-catalysts grants enhanced
      visible light absorption and photocatalytic performance, which provides another
      route for hetero-architecture materials design.

PMID- 29364300
TI  - Solvent control of charge transfer excited state relaxation pathways in [Fe(2,2'
      bipyridine)(CN)4]2.
AB  - The excited state dynamics of solvated [Fe(bpy)(CN)4]2-, where bpy = 2,2'
      bipyridine, show significant sensitivity to the solvent Lewis acidity. Using a
      combination of optical absorption and X-ray emission transient spectroscopies, we
      have previously shown that the metal to ligand charge transfer (MLCT) excited
      state of [Fe(bpy)(CN)4]2- has a 19 picosecond lifetime and no discernable
      contribution from metal centered (MC) states in weak Lewis acid solvents, such as
      dimethyl sulfoxide and acetonitrile.1,2 In the present work, we use the same
      combination of spectroscopic techniques to measure the MLCT excited state
      relaxation dynamics of [Fe(bpy)(CN)4]2- in water, a strong Lewis acid solvent.
      The charge-transfer excited state is now found to decay in less than 100
      femtoseconds, forming a quasi-stable metal centered excited state with a 13
      picosecond lifetime. We find that this MC excited state has triplet (3MC)
      character, unlike other reported six-coordinate Fe(ii)-centered coordination
      compounds, which form MC quintet (5MC) states. The solvent dependent changes in
      excited state non-radiative relaxation for [Fe(bpy)(CN)4]2- allows us to infer
      the influence of the solvent on the electronic structure of the complex.
      Furthermore, the robust characterization of the dynamics and optical spectral
      signatures of the isolated 3MC intermediate provides a strong foundation for
      identifying 3MC intermediates in the electronic excited state relaxation
      mechanisms of similar Fe-centered systems being developed for solar applications.

PMID- 29364301
TI  - Mechanistic insights into photoinduced damage of DNA and RNA nucleobases in the
      gas phase and in bulk solution.
AB  - DNA/RNA photohydrates represent a class of well-known biomolecular lesions formed
      by the absorption of near- to mid-UV light. They are formed via a photoinduced
      nucleophilic hydrolysis reaction in which water is split (via nucleobase
      sensitisation) into H + OH radicals. These nascent radicals can then add across
      C5[double bond, length as m-dash]C6, saturating the preexisting double bond. If
      unrepaired, such lesions can lead to mutagenic carcinogenesis, which is
      responsible for several forms of cancer. Using high-level electronic structure
      theory (CASPT2), we map the key excited-state reaction paths associated with the
      reactivity of DNA (guanine and thymine) and RNA (uracil) nucleobases with water.
      At the outset, we consider the intrinsic reactivity in the isolated gas phase -
      in which the water (cluster) + chromophore complex is free from environmental
      perturbations. We then extrapolate the thymine nucleobase to the bulk DNA
      environment in aqueous solution in order to ascertain the relative importance of
      hydrate formation in a more complex biological environment. In this latter study
      we use high-level mixed quantum/classical (QM/MM: CASPT2/AMBER) methods.

PMID- 29364302
TI  - Effects of a combined intervention with a lentil protein hydrolysate and a mixed
      training protocol on the lipid metabolism and hepatic markers of NAFLD in Zucker
      rats.
AB  - Metabolic syndrome is a cluster of metabolic alterations characterized by central
      obesity, dyslipidemia, elevated plasma glucose, insulin resistance (IR) and non
      alcoholic fatty liver disease (NAFLD). In this study, a combined intervention of
      a lentil protein hydrolysate and a mixed training protocol was assessed in an
      animal experimental model of genetic obesity and metabolic syndrome. Thirty-two
      male obese and 32 lean Zucker rats were divided into eight different experimental
      groups. Rats performed a mixed exercise protocol or had a sedentary lifestyle and
      were administered a lentil protein hydrolysate or placebo. Daily food intake,
      weekly body weight gain, plasma parameters of glucose and lipid metabolisms, body
      composition, hepatic weight, total fat content and fatty acid profile, as well as
      gene expression of lipogenic and lipolytic nuclear transcription factors and
      their target genes were measured. Obese Zucker rats exhibited higher body and
      liver weight and fat content than did their lean counterparts. Such alterations
      were related to modifications in aerobic capacity, plasma biochemical parameters
      of glucose and lipid metabolisms, hepatic fatty acid profile and gene expression
      of nuclear transcription factors SREBP1c, PPARalpha, LXR and associated lipogenic
      and lipolytic enzymes. The interventions tested did not affect body weight gain
      but improved aerobic capacity, reduced hepatomegalia and steatosis associated
      with NAFLD and relieved the adverse effects produced by this condition in glucose
      and lipid metabolisms through the modulation in the expression of different genes
      involved in diverse metabolic pathways.

PMID- 29364303
TI  - Nanocracking and metallization doubly defined large-scale 3D plasmonic sub-10 nm
      gap arrays as extremely sensitive SERS substrates.
AB  - Considering the technological difficulties in the existing approaches to form
      nanoscale gaps, a convenient method to fabricate three-dimensional (3D) sub-10 nm
      Ag/SiNx gap arrays has been demonstrated in this study, controlled by a
      combination of stress-induced nanocracking of a SiNx nanobridge and Ag nanofilm
      deposition. This scalable 3D plasmonic nanogap is specially suspended above a
      substrate, having a tunable nanogap width and large height-to-width ratio to form
      a nanocavity underneath. As a surface-enhanced Raman scattering (SERS) substrate,
      the 3D Ag/SiNx nanogap shows a large Raman enhancement factor of ~108 and
      extremely high sensitivity for the detection of Rhodamine 6G (R6G) molecules,
      even down to 10-16 M, indicating an extraordinary capability for single-molecule
      detection. Further, we verified that the Fabry-Perot resonance occurred in the
      deep SiNx nanocavity under the Ag nanogap and contributed prominently to a
      tremendous enhancement of the local field in the Ag-nanogap zone and hence
      ultrasensitive SERS detection. This method circumvents the technological
      limitations to fabricate a sub-10 nm metal nanogap with unique features for wide
      applications in important scientific and technological areas.

PMID- 29364304
TI  - A red-emitting fluorescent probe for hydrogen sulfide in living cells with a
      large Stokes shift.
AB  - A red-emitting fluorescent probe was developed for the sensitive and selective
      detection of H2S. Upon treatment with H2S, this probe exhibited a remarkable
      fluorescence enhancement (10 fold) with a large Stokes shift (125 nm). The
      detection limit of this probe was as low as 5.7 nM based on S/N = 3. The
      application of this probe in the detection of intracellular H2S in living cells
      is successfully demonstrated.

PMID- 29364306
TI  - Synthesis of a novel HER2 targeted aza-BODIPY-antibody conjugate: synthesis,
      photophysical characterisation and in vitro evaluation.
AB  - We herein report the synthesis and analysis of a novel aza-BODIPY-antibody
      conjugate, formed by controlled and regioselective bioconjugation methodology.
      Employing the clinically relevant antibody, which targets HER2 positive cancers,
      represents an excellent example of an antibody targeting strategy for this class
      of near-IR emitting fluorophore. The NIR fluorescence and binding properties were
      validated through in vitro studies using live cell confocal imaging.

PMID- 29364307
TI  - Solid-state one-way photoisomerisation of Z,E,Z-1,6-(4,4'-diphenyl)hexa-1,3,5
      triene dicarboxylate examined using higher-order derivative spectra and powder
      XRD patterns.
AB  - Higher order derivative spectra were applied at first to one-way ZEZ-to-EEE
      photoisomerisation of dimethyl ester (ZEZ-DPH1) of the titled compound in a
      methylcyclohexane solution. Many common crossing points emerged in UV-induced
      derivative-spectral changes to reveal the direct ZEZ-to-EEE photoisomerisation
      without the transient formation of an intermediate to suggest the bicycle-pedal
      mechanism. The solid-state photoisomerisation was subsequently monitored by
      tracing changes in the fourth-order derivatives of absorption spectra of a thin
      crystalline layer of ZEZ-DPH1 prepared by the drop-casting method, because the
      distortion of absorption spectra due to light scattering is cancelled. It was
      suggested that the solid-state photochemical event consists of three steps: fast
      ZEZ-to-EEE photoisomerisation, a subsequent slow ZEZ-to-EEE photoisomerisation
      and very slow disappearance of the EEE-isomer. Studies on powder XRD were also
      carried out for a drop-cast solid layer of ZEZ-DPH1 to disclose the coexistence
      of a crystal form other than the original one, and the former exhibited faster
      ZEZ-to-EEE photoisomerisation when compared with the original crystal form. The
      results revealed by XRD analysis are in line with those obtained by higher-order
      derivative spectra, confirming the solid-state one-way photoisomerisation to take
      place through the bicycle-pedal process.

PMID- 29364305
TI  - Engineered photoproteins that give rise to photosynthetically-incompetent
      bacteria are effective as photovoltaic materials for biohybrid
      photoelectrochemical cells.
AB  - Reaction centre/light harvesting proteins such as the RCLH1X complex from
      Rhodobacter sphaeroides carry out highly quantum-efficient conversion of solar
      energy through ultrafast energy transfer and charge separation, and these pigment
      proteins have been incorporated into biohybrid photoelectrochemical cells for a
      variety of applications. In this work we demonstrate that, despite not being able
      to support normal photosynthetic growth of Rhodobacter sphaeroides, an engineered
      variant of this RCLH1X complex lacking the PufX protein and with an enlarged
      light harvesting antenna is unimpaired in its capacity for photocurrent
      generation in two types of bio-photoelectrochemical cells. Removal of PufX also
      did not impair the ability of the RCLH1 complex to act as an acceptor of energy
      from synthetic light harvesting quantum dots. Unexpectedly, the removal of PufX
      led to a marked improvement in the overall stability of the RCLH1 complex under
      heat stress. We conclude that PufX-deficient RCLH1 complexes are fully functional
      in solar energy conversion in a device setting and that their enhanced structural
      stability could make them a preferred choice over their native PufX-containing
      counterpart. Our findings on the competence of RCLH1 complexes for light energy
      conversion in vitro are discussed with reference to the reason why these PufX
      deficient proteins are not capable of light energy conversion in vivo.

PMID- 29364309
TI  - Solvent incorporated sequential [3 + 2] annulation/substitution reaction of
      azomethine imines and propargyl sulfur ylide.
AB  - A novel solvent incorporated sequential [3 + 2] cycloaddition/substitution
      reaction of azomethine imines with propargyl sulfur ylide was developed. In the
      actual three-component reaction, propargyl sulfur ylide acts as a dipole reagent
      to furnish the annulation with azomethine imines, followed by the protic solvents
      acting as nucleophiles. The simple, mild, catalyst-free and practical protocol
      allows for the formation of N,N-bicyclic pyrazolidinones in moderate to excellent
      yields. Further transformation and gram-scale operations could also be achieved
      efficiently.

PMID- 29364308
TI  - Construction of tunable peptide nucleic acid junctions.
AB  - We report here the construction of 3-way and 4-way peptide nucleic acid (PNA)
      junctions as basic structural units for PNA nanostructuring. The incorporation of
      amino acid residues into PNA chains makes PNA nanostructures with more structural
      complexity and architectural flexibility possible, as exemplified by building 3
      way PNA junctions with tunable nanopores. Given that PNA nanostructures have good
      thermal and enzymatic stabilities, they are expected to have broad potential
      applications in biosensing, drug delivery and bioengineering.

PMID- 29364310
TI  - Well-defined silver conductive pattern fabricated on polyester fabric by screen
      printing a dopamine surface modifier followed by electroless plating.
AB  - Herein, we develop a novel method to fabricate silver conductive patterns on
      polyester fabric (PET) by screen printing dopamine (DOPA) tracks first, then
      reducing silver ions with polydopamine (PDA) tracks, which are self-polymerized
      from dopamine (DOPA), and finally electroless plating. Polydopamine (PDA)
      definitely adheres to the surface of the fabric and reduces the silver ions to
      initiate the electroless plating. This process is confirmed by Fourier transform
      infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy
      dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS). The
      conductivity of the well-defined silver patterns on the PET fabric is 0.86 Omega
      sq-1. In addition, the electronic patterns fabricated via the proposed method
      maintains their function under cyclic bending and Scotch(r)-tape tests, which
      indicates their great potential for application in flexible devices and wearable
      electronics.

PMID- 29364311
TI  - Spherical network contraction forms microtubule asters in confinement.
AB  - Microtubules and motor proteins form active filament networks that are critical
      for a variety of functions in living cells. Network topology and dynamics are the
      result of a self-organisation process that takes place within the boundaries of
      the cell. Previous biochemical in vitro studies with biomimetic systems
      consisting of purified motors and microtubules have demonstrated that confinement
      has an important effect on the outcome of the self-organisation process. However,
      the pathway of motor/microtubule self-organisation under confinement and its
      effects on network morphology are still poorly understood. Here, we have
      investigated how minus-end directed microtubule cross-linking kinesins organise
      microtubules inside polymer-stabilised microfluidic droplets of well-controlled
      size. We find that confinement can impose a novel pathway of microtubule aster
      formation proceeding via the constriction of an initially spherical
      motor/microtubule network. This mechanism illustrates the close relationship
      between confinement, network contraction, and aster formation. The spherical
      constriction pathway robustly produces single, well-centred asters with
      remarkable reproducibility across thousands of droplets. These results show that
      the additional constraint of well-defined confinement can improve the robustness
      of active network self-organisation, providing insight into the design principles
      of self-organising active networks in micro-scale confinement.

PMID- 29364314
TI  - Selective cancer treatment via photodynamic sensitization of hypoxia-responsive
      drug delivery.
AB  - The precise and selective delivery of chemodrugs into tumors represents a
      critical requirement for anti-cancer therapy. Intelligent delivery systems that
      are responsive to a single internal or external stimulus often lack sufficient
      cancer selectivity, which compromises the drug efficacy and induces undesired
      side effects. To overcome this dilemma, we herein report a cancer-targeting
      vehicle which allows highly cancer-selective drug release in response to cascaded
      external (light) and internal (hypoxia) dual triggers. In particular, doxorubicin
      (DOX)-loaded, hypoxia-dissociable nanoparticles (NPs) were prepared from self
      assembled polyethylenimine-nitroimidazole (PEI-NI) micelles that were further co
      assembled with hyaluronic acid-Ce6 (HC). Upon accumulation in tumor cells, tumor
      site-specific light irradiation (660 nm, 10 mW cm-2) generated high levels of
      reactive oxygen species (ROS) and greatly enhanced the hypoxic levels to induce
      NP dissociation and accordingly DOX release. A synergistic anti-cancer efficacy
      between DOX-mediated chemotherapy and Ce6-mediated photodynamic therapy (PDT) was
      thus achieved, resulting in reduced side effects to normal tissues/cells. This
      study therefore provides an effective method to control the cancer-specific drug
      delivery by responding to cascaded multiple triggers, and it renders promising
      applications for the programmed combination of chemotherapy and PDT toward cancer
      treatment.

PMID- 29364327
TI  - Correction: Engineering highly sensitive whole-cell mercury biosensors based on
      positive feedback loops from quorum-sensing systems.
AB  - Correction for 'Engineering highly sensitive whole-cell mercury biosensors based
      on positive feedback loops from quorum-sensing systems' by Sheng Cai, et al.,
      Analyst, 2018, DOI: 10.1039/c7an00587c.

PMID- 29364328
TI  - The marginal fit of lithium disilicate crowns: Press vs. CAD/CAM.
AB  - This study aimed to compare the vertical marginal gap of teeth restored with
      lithium disilicate crowns fabricated using CAD/CAM or by pressed ceramic
      approach. Twenty mandibular third molar teeth were collected after surgical
      extractions and prepared to receive full veneer crowns. Teeth were optically
      scanned and lithium disilicate blocks were used to fabricate crowns using CAD/CAM
      technique. Polyvinyl siloxane impressions of the prepared teeth were made and
      monolithic pressed lithium disilicate crowns were fabricated. The marginal gap
      was measured using optical microscope at 200* magnification (Keyence VHX-5000,
      Japan). Statistical analysis was performed using Wilcoxon test. The lithium
      disilicate pressed crowns had significantly smaller (p = 0.006) marginal gaps (38
      +/- 12 MUm) than the lithium disilicate CAD/CAM crowns (45 +/- 12 MUm). This
      research indicates that lithium disilicate crowns fabricated with the press
      technique have measurably smaller marginal gaps compared with those fabricated
      with CAD/CAM technique within in vitro environments. The marginal gaps achieved
      by the crowns across all groups were within a clinically acceptable range.

PMID- 29364329
TI  - Oral health related quality of life among pregnant women: a randomized controlled
      trial.
AB  - The aim of the present study was to compare negative impacts of oral conditions
      in Oral Heath Related Quality of Life (OHRQoL) assessed by the Oral Health Impact
      Profile-14 (OHIP-14) scores in pregnant women receiving or not comprehensive
      periodontal treatment. This randomized controlled clinical trial included
      pregnant women aged between 18 and 35 years old. Participants were randomized in
      a test group with 96 and a control group with 114 women. Patients in the test
      group received comprehensive periodontal treatment, supra and subgingival scaling
      and root-planning and periodontal maintenance appointments. The OHIP-14 was
      applied before and after treatment. The primary outcome was changes in OHIP-14
      scores after follow-up period. The impact of having received or not comprehensive
      periodontal treatment on the change of the OHIP-14 scores was also investigated.
      Both groups showed significant reduction in OHIP-14 scores and effect size for
      the test group was 0.60 and 0.36 for the control group. Multinomial logistic
      regression analysis showed that participants of the control group had 5.9-fold
      odds (CI 95% 1.88-18.52) of worsening in OHIP-14 scores and their perception of
      oral conditions in relation to test group. Comprehensive periodontal treatment
      during pregnancy can reduce the negative impacts in OHRQoL.

PMID- 29364330
TI  - Teaching and learning nursing management in the hospital context: an approach in
      the light of Pichon-Riviere.
AB  - OBJECTIVE: Analyze the articulation of students, professors (supervisors of the
      undergraduate practicum) and nursing professionals in teaching and learning
      nursing management at graduation in a public university hospital. METHOD: This is
      a study of qualitative approach, anchored in the operative group reference of
      Pichon-Riviere. Data collection was held between October 2013 and September 2014
      and consisted of a self-administered questionnaire, participant observation and
      focus group. The information was submitted to thematic analysis. RESULTS: The
      thematic analysis of the corpus resulted in four themes: the unknown and the
      inevitable; in coming and going, attitudes, values and new bonding; the dialogue
      and ways of acting in the teaching/learning; the emergence of praxis. CONCLUSION:
      The articulation among students, supervisors and nursing professionals occurring
      in a coming and going of attitudes, values and new bonding, in which the dialogue
      enables ways of acting in the teaching/learning of nursing management in
      graduation, allowing the emergence of praxis.

PMID- 29364331
TI  - Is HCV elimination possible in prison?

PMID- 29364332
TI  - Criminal characteristics of a group of primary criminals diagnosed with aspd:
      approach to criminal recidivis.
AB  - INTRODUCTION: Antisocial personality disorder (ASPD) is commonly associated with
      the risk of criminal recidivism. Knowing more about the factors associated with
      this pattern of behaviour can help with the design of effective prevention
      strategies. The purpose of this article is to establish if there are differences
      in socio-criminogenic variables of a group of criminals sentenced for the first
      time and with APSD compared to another group of first-time offenders who do not
      present this disorder. MATERIALS AND METHODS: Analytical observation study of 70
      men classified into 2 groups according to the presence of ASPD TPA (n=47; age:
      29.98+/-7.8 years) or absence of ASPD (n=23; age: 32.35+/-8.7 years). RESULTS:
      The inmates with ASPD showed higher frequencies of current consumption of
      psychoactive substances (31.9%), criminal associations and simultaneous use of
      psychoactive substances (70.2%), having committed the crime under the effects of
      a psychoactive substance (55.3%), not having the possibility of distancing
      themselves from criminal associations (83%) and a lack of legal resources for
      proceedings for defence and release (76.6%). DISCUSSION: This sample contains a
      group of variables called dynamic that are more commonly present amongst first
      time offenders with ASPD; said variables have been associated as major predictors
      of recidivism. Given that they are regarded as dynamic, they may well be
      modifiable.

PMID- 29364333
TI  - Emotional well-being amongst female inmates in prisons: the relevance of their
      addictive history and their country of origin.
AB  - OBJECTIVE: To know more about the emotional well-being of women held in prisons
      in Spain by analyzing the state of mental health they present and investigating
      the factors that affect them. MATERIAL AND METHODS: A sample of 434 inmates in
      Spanish penitentiary centers was studied. An ad hoc designed questionnaire was
      used and a logistic regression analysis was conducted to determine the variables
      and to what extent they influence emotional well-being. RESULTS: The existence of
      a statistically significant relationship between the well-being stages and the
      origin variables (region of origin of the women) and the history of substance
      addiction were confirmed. No significant relationship has been found for well
      being levels from other variables (maternity, social or family support, gender
      violence or having or not having a partner). CONCLUSIONS: Having a problematic
      history of drug use negatively affects the levels of emotional well-being of
      women detained in prisons. The low levels of substance use in women of Latin
      American origin is related to their more positive levels of emotional well-being.

PMID- 29364334
TI  - Extrahepatic manifestations associated with Chronic Hepatitis C Virus Infection.
AB  - Chronic hepatitis C virus (HCV) infection has been associated with both organ
      specific and systemic autoimmune diseases, with cryoglobulinemia being the most
      frequent associated disease. Experimental, virologic, and clinical evidence have
      demon-strated a close association between HCV infection and some systemic
      autoimmune diseases, especially Sjogren's syndrome, but also rheumatoid arthritis
      and lupus. A higher prevalence of hematological processes has also been described
      in patients with HCV infection, including cytopenias and lymphoproliferative
      disorders (B-cell lymphoma). In addition, patients with chronic HCV infection
      have a higher frequency of other extrahepatic manifestations including endocrine,
      metabolic and cardiovascular disorders that may worse the prognosis of patients,
      along with neuropsychiatric manifestations and general symptoms that have a
      significant influence on the quality of life of the patient. Direct-acting
      antiviral therapies (DAAs) that have recently begun to be used are providing the
      opportunity to effectively cure chronic HCV infection and reduce the burden of
      both hepatic and extrahepatic complications.

PMID- 29364335
TI  - Congenital syphilis in 2 children in a Bolivian prison.

PMID- 29364336
TI  - Structural and mechanical properties of a giomer-based bulk fill restorative in
      different curing conditions.
AB  - The main goal of this study was to compare the polymerization degree of bulk-fill
      giomer resin cured with three different light-curing units (LCUs): a polywave
      third-generation (Valo); a monowave (DemiUltra: DU); and a second-generation LED
      (Optima 10: Opt) LCUs by using structural and mechanical properties. Giomer
      samples of 2 and 4 mm cured with three LCUs were employed in vitro analysis. The
      degree of curing (DC%) was determined with Fourier-Transform Infrared
      Spectroscopy (FTIR). Microstructural features were observed with scanning
      electron microscopy (SEM). Flexural strength (FS), compression strength (CS),
      elastic modulus and fracturing strain were determined for mechanical properties.
      Surface microhardness (SMH) values were also measured. Oneway ANOVA, two-way
      analysis of variance and Tukey multiple comparison tests were used for
      statistically analyzing the FS and SMH. DC% values were 58.2, 47.6, and 39.7 for
      the 2 mm samples cured with DU, Opt., and Valo LCUs, respectively. DC% values of
      the 4 mm samples were 50.4, 44.6, and 38.2 for DU, Opt, and Valo, respectively.
      SMH values were Valo, Opt<DU at top of the samples; Valo<DU, Opt at 2 mm, and DU,
      Valo<Opt at 4 mm depth. Giomer samples cured with Opt and DU exhibited higher FS
      values than Valo. CS values were similar but compressive modulus and fracturing
      strain (%) varied depending on the curing protocol. Based on the results, it can
      be concluded that curing device and protocol strongly affect crosslinking
      reactions and thus DC%, SMH, compressive modulus and strain at break values.
      Consequently, it can be deduced that curing protocol is possibly the most
      important parameter for microstructure formation of highly-filled composite
      restoratives because it may bring some structural defects and physical frailties
      on restorations due to lower degree of polymerization.

PMID- 29364337
TI  - To what extent does hyaluronic acid affect healing of xenografts? A
      histomorphometric study in a rabbit model.
AB  - Among the many graft materials that have been used for the treatment of bone
      defects in oral and maxillofacial regions is xenograft. To improve
      osteoconductive effects of xenografts, they have been combined with various
      biocompatible materials, such as hyaluronic acid and bone morphogenetic protein.
      To determine bone-healing capacity of high molecular weight hyaluronic acid (HA)
      combined with xenograft in rabbit calvarial bone defects. Ten adult male New
      Zealand rabbits (mean weight 3 kg) were included in the study. Three 6-mm
      diameter bicortical cranial defects were created on calvarial bone of all
      rabbits. These defects were filled as follows: a) xenograft; b) HA+xenograft; c)
      autograft. One month after the first operation, rabbits were sacrificed.
      Specimens were evaluated histomorphometrically. Considering multiple comparisons,
      differences regarding new bone were statistically significant between all groups
      (p<0.05). The volume of residual graft was significantly decreased in HA group
      compared to xenograft group (p=0.035). Marrow space, trabecular thickness (TbTh),
      trabecular width (TbWi), trabecular separation (TbSp), and number of node: number
      of terminus (NNd:NTm) in the autograft group were significantly better than
      xenograft and HA groups (p<0.05). However, regarding marrow space, TbTh, TbWi,
      TbSp, and NNd:NTm values, xenograft and HA groups showed similar results and the
      difference were not significant (p>0.05). These results support that high
      molecular weight hyaluronic acid could contribute to the healing of xenograft by
      improving the percentage of new bone formation and reducing the percentage of
      residual graft. However, HA did not significantly affect the quality of newly
      formed bone assessed by microarchitectural parameters.

PMID- 29364338
TI  - Influence of skin cold sensation threshold in the occurrence of dental
      sensitivity during dental bleaching: a placebo controlled clinical trial.
AB  - This study verified the occurrence of dental sensitivity in patients submitted to
      a 35% hydrogen peroxide based product (Whiteness HP Maxx 35% - FGM), skin cold
      sensation threshold (SCST) and its influence on dental sensitivity. Sixty
      volunteers were divided into 4 groups (n = 15), according to SCST (low: GI and
      GIII, and high: GII and IV) and bleaching treatment (hydrogen peroxide: GI and
      GII, and placebo: GIII and GIV). SCST was determined in the inner forearm for 6
      different times using a neurosensory analyzer, the TSA II (Medoc Advanced Medical
      Systems, Ramat Yishai, Northern District, Israel). Dental sensitivity
      measurements were performed 10 different times using a thermal stimulus and an
      intraoral device attached to TSA II, positioned in the buccal surface of the
      upper right central incisor. Spontaneous dental sensitivity was also determined
      using the Visual Analogue Scale (VAS). Data were submitted to Student's t-test
      and Pearson's Correlation Test (alpha=0.05). SCST remained the same during
      bleaching treatment. Distinct responses of dental sensitivity were found in
      patients with low and high SCST during the first and third bleaching session
      (p<=0.05). The teeth submitted to the bleaching treatment became more sensitive
      to cold than those treated with placebo. Moreover, data obtained with TSA and VAS
      presented moderate correlation. Bleaching treatment increased dental sensitivity
      and skin cold sensation threshold might represent a determining factor in this
      occurrence, since low and high SCST patients had different responses to the
      thermal stimulus in the teeth.

PMID- 29364339
TI  - Effect of erosive challenges on deciduous teeth undergoing restorative procedures
      with different adhesive protocols - an in vitro study.
AB  - To evaluate the effect of erosive challenges on the tooth- restoration interface
      of deciduous teeth treated with different adhesive protocols. Deciduous molars
      were cut mesiodistally, then embedded, abraded and polished (n=80). Samples were
      randomly divided according to the adhesive system used into: G1 (Adper Single
      Bond2(r), etch-and-rinse), G2 (Universal Single Bond(r), self-etching), G3
      (OptibondFL(r), etch-and-rinse with Fluoride) and G4 (BondForce(r), self-etching
      with Fluoride). After standardized cavity preparation (2 mm diameter x 2 mm
      depth), adhesive systems were applied and samples were restored (composite resin
      Z350(r)). Half of the samples were exposed to erosive/abrasive cycles (n = 10,
      each adhesive group), and the other half (control group; n = 10) remained
      immersed in artificial saliva. For microleakage analysis, samples were submersed
      in methylene blue and analyzed at 40x magnifications. Cross-sectional
      microhardness (CSMH) was carried out (50 g/5 s) at 25 MUm, 50 MUm, and 100 MUm
      from the eroded surface and at 25 MUm, 75 MUm, and 125 MUm from the enamel bond
      interface. Regarding microleakage, 7.5% of the samples showed no dye
      infiltration, 30% showed dye infiltration only at the enamel interface, and 62.5%
      showed dye infiltration through the dentin-enamel junction, with no difference
      between groups (p>=0.05). No significant difference was observed in CSMH at
      different depths (two-way ANOVA, p>=0.05). We did not observe significant changes
      in microleakage or CSMH after erosive/abrasive challenges in deciduous teeth
      treated with different adhesive protocols (etch-and-rinse and self-etching
      adhesives, with and without fluoride).

PMID- 29364340
TI  - Microbiological and clinical effects of probiotics and antibiotics on nonsurgical
      treatment of chronic periodontitis: a randomized placebo- controlled trial with 9
      month follow-up.
AB  - The aim of this double-blind, placebo-controlled and parallel- arm randomized
      clinical trial was to evaluate the effects of Lactobacillus rhamnosus SP1
      containing probiotic sachet and azithromycin tablets as an adjunct to nonsurgical
      therapy in clinical parameters and in presence and levels of Tannerella
      forsythia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans.
      Forty-seven systemically healthy volunteers with chronic periodontitis were
      recruited and monitored clinically and microbiologically at baseline for 3, 6 and
      9 months after therapy. Subgingival plaque samples were collected from four
      periodontal sites with clinical attachment level >=1 mm, probing pocket depth >=4
      mm and bleeding on probing, one site in each quadrant. Samples were cultivated
      and processed using the PCR technique. Patients received nonsurgical therapy
      including scaling and root planing (SRP) and were randomly assigned to a
      probiotic (n=16), antibiotic (n = 16) or placebo (n = 15) group. L. rhamnosus SP1
      was taken once a day for 3 months. Azithromycin 500mg was taken once a day for 5
      days. All groups showed improvements in clinical and microbiological parameters
      at all time points evaluated. Probiotic and antibiotic groups showed greater
      reductions in cultivable microbiota compared with baseline. The placebo group
      showed greater reduction in number of subjects with P. gingivalis compared with
      baseline. However, there were no significant differences between groups. The
      adjunctive use of L. rhamnosus SP1 sachets and azithromycin during initial
      therapy resulted in similar clinical and microbiological improvements compared
      with the placebo group.

PMID- 29364341
TI  - Determination of the effective anticandidal concentration of denture cleanser
      tablets on some denture base resins.
AB  - Although the effectiveness of chemical cleansing against Candida albicans biofilm
      has been shown, the effective concentration of denture cleanser tablets has not
      been studied. The aim of this study was to assess the effect of three denture
      materials against Candida albicans biofilm and to determine effective
      concentrations of denture cleanser tablets. The surface-roughness of Acron-hiTM,
      QC-20TM and DeflexTM (n=45 per resin) resins was standardized by using a
      profilometer and their contact angle or surface free energy was calculated. C.
      albicans biofilm was formed on all three resins and were treated with Polident 3
      minTM, CoregaTM and FittydentTM cleanser solutions at various concentrations and
      both resin-biofilm and cleanser-biofilm interest were determined by using a MTT
      protocol according to the European Committee on Antimicrobial Susceptibility
      Testing's antifungal susceptibility testing (AFST-EUCAST). Scanning electron
      microscopy was used to compare the efficacy of different resin materials against
      C. albicans biofilm. Anticandidal activity and surface free energy statistical
      parameters were calculated by using 3-way and 1-way ANOVA, respectively (p<0.05).
      Polident 3 minTM and CoregaTM tablets significantly inhibited (p<0.05) the
      proliferation of C. albicans against all denture resins at 27-37 mg/mL. Scanning
      electron microscopy results indicated that there was no significant difference
      among resin specimens regarding biofilm formation on dentures. We failed to find
      a significant relationship between surface free energy and the anticandidal
      effect of resin types. However, the polarity value of the resins was
      statistically associated with their anticandidal activity. The polarity of the
      resins, the concentrations of tablets and the chemical content of the cleanser
      may directly affect C. albicans biofilm formations. Polident 3 minTM and CoregaTM
      tablets should be suggested for patients who use any denture resin types, whereas
      the FittydentTM tablet should only be proposed for those who use DeflexTM, when
      two tablets are dropped into 150 mL water.

PMID- 29364342
TI  - Alveolar bone repair with strontium- containing nanostructured carbonated
      hydroxyapatite.
AB  - This study aimed to evaluate bone repair in rat dental sockets after implanting
      nanostructured carbonated hydroxyapatite/sodium alginate (CHA) and nanostructured
      carbonated hydroxyapatite/sodium alginate containing 5% strontium microspheres
      (SrCHA) as bone substitute materials. Twenty male Wistar rats were randomly
      divided into two experimental groups: CHA and SrCHA (n=5/period/group). After one
      and 6 weeks of extraction of the right maxillary central incisor and biomaterial
      implantation, 5 MUm bone blocks were obtained for histomorphometric evaluation.
      The parameters evaluated were remaining biomaterial, loose connective tissue and
      newly formed bone in a standard area. Statistical analysis was performed by Mann
      Withney and and Wilcoxon tests at 95% level of significance. The
      histomorphometric results showed that the microspheres showed similar
      fragmentation and bio-absorbation (p>0.05). We observed the formation of new
      bones in both groups during the same experimental periods; however, the new bone
      formation differed significantly between the weeks 1 and 6 (p=0.0039) in both
      groups. The CHA and SrCHA biomaterials were biocompatible, osteoconductive and
      bioabsorbable, indicating their great potential for clinical use as bone
      substitutes.

PMID- 29364343
TI  - Randomized clinical trial of encapsulated and hand-mixed glass-ionomer ART
      restorations: one-year follow-up.
AB  - This prospective, randomized, split-mouth clinical trial evaluated the clinical
      performance of conventional glass ionomer cement (GIC; Riva Self-Cure, SDI),
      supplied in capsules or in powder/liquid kits and placed in Class I cavities in
      permanent molars by the Atraumatic Restorative Treatment (ART) approach. A total
      of 80 restorations were randomly placed in 40 patients aged 11-15 years. Each
      patient received one restoration with each type of GIC. The restorations were
      evaluated after periods of 15 days (baseline), 6 months, and 1 year, according to
      ART criteria. Wilcoxon matched pairs, multivariate logistic regression, and Gehan
      Wilcoxon tests were used for statistical analysis. Patients were evaluated after
      15 days (n=40), 6 months (n=34), and 1 year (n=29). Encapsulated GICs showed
      significantly superior clinical performance compared with hand-mixed GICs at
      baseline (p=0.017), 6 months (p=0.001), and 1 year (p=0.026). For hand-mixed GIC,
      a statistically significant difference was only observed over the period of
      baseline to 1 year (p=0.001). Encapsulated GIC presented statistically
      significant differences for the following periods: 6 months to 1 year (p=0.028)
      and baseline to 1 year (p=0.002). Encapsulated GIC presented superior cumulative
      survival rate than hand-mixed GIC over one year. Importantly, both GICs exhibited
      decreased survival over time. Encapsulated GIC promoted better ART performance,
      with an annual failure rate of 24%; in contrast, hand-mixed GIC demonstrated a
      failure rate of 42%.

PMID- 29364344
TI  - Psychopathological profile and quality of life of patients with oral lichen
      planus.
AB  - Oral lichen planus (OLP) is a chronic, multifocal, sometimes painful,
      inflammatory disease of the oral mucosa. OLP can predispose development of psycho
      emotional disorders. Until now, the relationship between the severity of lichen
      planus and the psychological profile of patients (psychological well-being,
      perceived stress and pain coping strategies) has never been studied. Study was
      conducted on 42 OLP patients. Number of sites involved, severity and activity
      score of OLP were evaluated. Psychological tests were used to evaluate patients'
      psycho-emotional condition. The mean duration time of symptomatic OLP was 43
      months. We detected that the longer the duration of subjective symptoms, the
      poorer the quality of life and the higher the level of perceived stress (PSS).
      Also, the higher the PSS results, the greater the anxiety and depression on
      Hospital Anxiety and Depression Scale (HADS). Likewise, higher level of
      depression in HADS was strongly correlated with worse quality of life. (p<=0.05).
      In this study, we detected a relationship between duration of the disease, level
      of perceived stress and quality of life. The longer the disease lasts, the higher
      it tends to catastrophize. This may influence development or increase of the
      anxiety and depression and may decrease patients' quality of life.

PMID- 29364345
TI  - Two mechanisms of oral malodor inhibition by zinc ions.
AB  - The aim of this study was to reveal the mechanisms by which zinc ions inhibit
      oral malodor. The direct binding of zinc ions to gaseous hydrogen sulfide (H2S)
      was assessed in comparison with other metal ions. Nine metal chlorides and six
      metal acetates were examined. To understand the strength of H2S volatilization
      inhibition, the minimum concentration needed to inhibit H2S volatilization was
      determined using serial dilution methods. Subsequently, the inhibitory activities
      of zinc ions on the growth of six oral bacterial strains related to volatile
      sulfur compound (VSC) production and three strains not related to VSC production
      were evaluated. Aqueous solutions of ZnCl2, CdCl2, CuCl2, (CH3COO)2Zn,
      (CH3COO)2Cd, (CH3COO)2Cu, and CH3COOAg inhibited H2S volatilization almost
      entirely. The strengths of H2S volatilization inhibition were in the order Ag+ >
      Cd2+ > Cu2+ > Zn2+. The effect of zinc ions on the growth of oral bacteria was
      strain-dependent. Fusobacterium nucleatum ATCC 25586 was the most sensitive, as
      it was suppressed by medium containing 0.001% zinc ions. Zinc ions have an
      inhibitory effect on oral malodor involving the two mechanisms of direct binding
      with gaseous H2S and suppressing the growth of VSC-producing oral bacteria.

PMID- 29364346
TI  - Debris extrusion and foraminal deformation produced by reciprocating instruments
      made of thermally treated NiTi wires.
AB  - To evaluate the amount of apically extruded debris, percentage of foraminal
      enlargement and apical foramen (AF) deformation that occurred during root canal
      preparation with different reciprocation systems: Reciproc, WaveOne (M-Wire), and
      ProDesign R (Shape Memory Technology Wire) at two different working lengths
      (WLs): 0.0 and 1.0 mm beyond the AF. The AF of 120 root canals in 60 mesial roots
      of mandibular molars were photographed with stereomicroscope and randomly
      assigned into four groups: manual, Reciproc (REC), WaveOne (WO), and ProDesign R
      (PDR); subsequently, they were further subdivided according to the WL (n=15).
      Teeth were instrumented, coupled to a dual collecting chamber, and then another
      photograph of each AF was captured. Extrusion was analysed by determining the
      weight of extruded debris. Each AF diameter was measured in pre- and post
      instrumentation images to determine deformation, which was analysed, and
      afterwards the final format of AFs was classified (circular/oval/deformed). We
      found no significant differences when analysing each system at different WLs.
      When considering each WL, REC and WO showed highest extrusion values (P<.05); for
      AF enlargement, differences were observed only for WO, when it was used beyond
      the AF; differences were observed among M-Wire groups beyond the AF (P<.05). AF
      deformation was observed in all groups; PDR showed the lowest AF deformation
      values at both WLs; M-Wire groups showed 50% strain beyond the AF. Authors
      concluded that beyond the apical limit, the alloy and taper are important aspects
      when considering extrusion and deformation.

PMID- 29364347
TI  - The Challenge of Eight Years as Arquivos Brasileiros de Cardiologia Editor-in
      Chief.

PMID- 29364348
TI  - Potential of Family Health Strategy Against Cardiovascular Disease.

PMID- 29364350
TI  - Bone-Marrow-Derived Mesenchymal Stromal Cells (MSC) from Diabetic and Nondiabetic
      Rats Have Similar Therapeutic Potentials.
AB  - BACKGROUND: Diabetes mellitus is a severe chronic disease leading to systemic
      complications, including cardiovascular dysfunction. Previous cell therapy
      studies have obtained promising results with the use bone marrow mesenchymal
      stromal cells derived from healthy animals (MSCc) in diabetes animal models.
      However, the ability of MSC derived from diabetic rats to improve functional
      cardiac parameters is still unknown. OBJECTIVES: To investigate whether bone
      marrow-derived MSC from diabetic rats (MSCd) would contribute to recover
      metabolic and cardiac electrical properties in other diabetic rats. METHODS:
      Diabetes was induced in Wistar rats with streptozotocin. MSCs were characterized
      by flow cytometry, morphological analysis, and immunohistochemistry. Cardiac
      electrical function was analyzed using recordings of ventricular action
      potential. Differences between variables were considered significant when p <
      0.05. RESULTS: In vitro properties of MSCc and MSCd were evaluated. Both cell
      types presented similar morphology, growth kinetics, and mesenchymal profile, and
      could differentiate into adipogenic and osteogenic lineages. However, in an assay
      for fibroblast colony-forming units (CFU-F), MSCd formed more colonies than MSCc
      when cultured in expansion medium with or without hydrocortisone (1 uM). In order
      to compare the therapeutic potential of the cells, the animals were divided into
      four experimental groups: nondiabetic (CTRL), diabetic (DM), diabetic treated
      with MSCc (DM + MSCc), and diabetic treated with MSCd (DM + MSCd). The treated
      groups received a single injection of MSC 4 weeks after the development of
      diabetes. MSCc and MSCd controlled hyperglycemia and body weight loss and
      improved cardiac electrical remodeling in diabetic rats. CONCLUSIONS: MSCd and
      MSCc have similar in vitro properties and therapeutic potential in a rat model of
      diabetes induced with streptozotocin.

PMID- 29364349
TI  - Characterization of Cardiopulmonary Exercise Testing Variables in Patients with
      Endomyocardial Fibrosis after Endocardial Resection.
AB  - BACKGROUND: Endomyocardial fibrosis (EMF) is a rare disease, characterized by
      diastolic dysfunction which leads to reduced peak oxygen consumption (VO2).
      Cardiopulmonary exercise testing (CPET) has been proved to be a fundamental tool
      to identify central and peripheral alterations. However, most studies prioritize
      peak VO2 as the main variable, leaving aside other important CPET variables that
      can specify the severity of the disease and guide the clinical treatment.
      OBJECTIVE: The aim of this study was to evaluate central and peripheral
      limitations in symptomatic patients with EMF by different CPET variables.
      METHODS: Twenty-six EMF patients (functional class III, NYHA) were compared with
      15 healthy subjects (HS). Functional capacity was evaluated using CPET and
      diastolic and systolic functions were evaluated by echocardiography. RESULTS: Age
      and gender were similar between EMF patients and HS. Left ventricular ejection
      fraction was normal in EMF patients, but decreased compared to HS. Peak heart
      rate, peak workload, peak VO2, peak oxygen (O2) pulse and peak pulmonary
      ventilation (VE) were decreased in EMF compared to HS. Also, EMF patients showed
      increased Delta heart rate /Delta oxygen uptake and Delta oxygen uptake /Delta
      work rate compared to HS. CONCLUSION: Determination of the aerobic capacity by
      noninvasive respiratory gas exchange during incremental exercise provides
      additional information about the exercise tolerance in patients with EMF. The
      analysis of different CPET variables is necessary to help us understand more
      about the central and peripheral alterations cause by both diastolic dysfunction
      and restrictive pattern.

PMID- 29364351
TI  - Lung Ultrasound: The Cardiologists' New Friend.

PMID- 29364352
TI  - Case 6/2017 - A 28-Year-Old Man with Anasarca And Restrictive Heart Disease.

PMID- 29364353
TI  - Superior Vena Cava Syndrome after Radiofrequency Catheter Ablation for Atrial
      Fibrillation.

PMID- 29364354
TI  - Diagnosis and Treatment of Rare Complication after Endomyocardial Biopsy.

PMID- 29364355
TI  - Cardiac Autonomic Functions May be Influenced by Body WeightReplySensitivity,
      specificity and predictive value of heart rate variability indices in type 1
      diabetes mellitusGeometric indexes of heart rate variability in obese and
      eutrophic childrenFractal correlation of heart rate variability in obese
      childrenAnalysis of cardiac autonomic modulation in obese and eutrophic
      childrenImpact of obesity on autonomic modulation, heart rate and blood pressure
      in obese young people.

PMID- 29364356
TI  - Nascer no Brasil: the presence of a companion favors the use of best practices in
      delivery care in the South region of Brazil.
AB  - OBJECTIVE To analyze if the presence of a companion favors the use of best
      practices in the delivery care in the South region of Brazil. METHODS This is a
      cross-sectional analysis of the longitudinal study Nascer no Brasil. We analyzed
      data from 2,070 women from the South region of Brazil who went into labor. The
      data were collected between February and August 2011, by interviews and medical
      records. We performed a bivariate and multivariate analysis, calculating the
      crude and adjusted prevalence ratios using Poisson regression with robust
      variance estimation. The level of significance adopted was 5%. RESULTS Most women
      had a companion during labor (51.7%), but few remained during delivery (39.4%) or
      cesarean section (34.8%). Less than half of the women had access to several
      recommended practices, while non-recommended practices continue to be performed.
      In the model adjusted for age, education level, source of payment for the
      delivery, parity, and score of the Brazilian Association of Market Research
      Institutes, the presence of a companion was statistically associated with a
      greater supply of liquids and food (aPR = 1.34), dietary prescription (aPR =
      1.34), use of non-pharmacological methods for pain relief (aPR = 1.37), amniotomy
      (aPR = 1.10), epidural or spinal analgesia (aPR = 1.84), adoption of non
      lithotomy position in the delivery (aPR = 1.77), stay in the same room during
      labor, delivery, and postpartum (aPR = 1.62), skin-to-skin contact in the
      delivery (aPR = 1.81) and cesarean section (PR = 2.43), as well as reduced use of
      the Kristeller maneuver (aPR = 0.67), trichotomy (aPR = 0.59), and enema (aPR =
      0.49). CONCLUSIONS In the South region of Brazil, most women do not have access
      to the best practices in addition to undergoing several unnecessary
      interventions. The presence of a companion is associated with several beneficial
      practices and the reduction in some interventions, although other interventions
      are not impacted.

PMID- 29364357
TI  - Effectiveness of a web-based intervention in reducing binge drinking among
      nightclub patrons.
AB  - OBJECTIVE To evaluate the effectiveness of a web-based intervention in reducing
      binge drinking among nightclub patrons after six months. METHODS We carried out a
      website survey with probabilistic sample in 31 nightclubs in the city of Sao
      Paulo, Brazil, which originated a randomized controlled trial with 1,057
      participants. Those classified as problem drinkers (n = 465) using the Alcohol
      Use Disorders Identification Test were randomized into two study groups -
      intervention and control. The web-based intervention consisted of exposing the
      participants to a normative feedback screen about their alcohol consumption,
      characterizing the risks associated with amount consumed, money spent on drinks,
      drinking and driving, risk classification of Alcohol Use Disorders Identification
      Test, and tips to reduce damage. RESULTS There was a significant reduction in the
      practice of binge drinking in the week estimated at 38% among participants in the
      intervention group after six months (p < 0.05). However, there was no significant
      reduction in the outcomes when we analyzed the intervention and control groups
      and at baseline and after sixth months, simultaneously. CONCLUSIONS We cannot
      conclude that digital tools reduce the pattern of binge drinking among party
      goers in Sao Paulo. More studies are needed with this methodology because of its
      attractiveness to this type of group, given the privacy and speed that
      personalized information is transmitted.

PMID- 29364359
TI  - Monitoring and treating fetuses with gastroschisis using the Svetliza
      Reducibility Index (SRI) and the EXIT-like procedure - a novel approach.

PMID- 29364358
TI  - Spanish adaptation and validation of the supportive & palliative care indicators
      tool - SPICT-ESTM.
AB  - OBJECTIVE To culturally adapt and validate the SPICTTM to Spanish, which is a
      brief and simple tool to support a better identification of chronic patients who
      have palliative care needs. METHODS For this study, we designed a multicenter and
      national project between the centers of Galicia, Balearic Islands, and Andalusia.
      For the process of translation and cross-cultural adaptation of the SPICTTM to
      Spanish, we followed the steps proposed by Beaton et al. with successive
      translations and subsequent consensus of experts using the debriefing
      methodology. After the content validation was completed, the psychometric
      properties were validated. A prospective longitudinal study was designed with 188
      patients from Galicia, the Balearic Islands, and Andalusia. The internal
      consistency and reliability of the test and retest was analyzed for 10 days by
      the same researcher. RESULTS For more than 90% of the participants of the SPICT
      ESTM, it seems simple to be filled out, and they consider it written in an
      understandable language. The average time to apply the questionnaire without
      prior knowledge was 4 minutes and 45 seconds. To evaluate the internal
      consistency of the instrument, we used the Kuder-Richardson formula 20. Internal
      consistency is 0.71. The agreement index of the Kappa test is between 0.983 and
      0.797 for the different items. CONCLUSIONS In this study, we demonstrate the
      equivalence of content with the original. In addition, the validation of the
      psychometric properties establishes that the SPICT-ESTM maintains adequate
      reliability and stability. If we add the satisfaction shown by the professionals
      and the ease of use, the SPICT-ESTM is an adequate tool for the identification of
      palliative patients with chronic diseases and palliative care needs.

PMID- 29364360
TI  - Novel multidisciplinary approach to monitor and treat fetuses with gastroschisis
      using the Svetliza Reducibility Index and the EXIT-like procedure.
AB  - OBJECTIVE: To describe our initial experience with a novel approach to follow-up
      and treat gastroschisis in "zero minute" using the EXITlike procedure. METHODS:
      Eleven fetuses with prenatal diagnosis of gastroschisis were evaluated. The
      Svetliza Reductibility Index was used to prospectively evaluate five cases, and
      six cases were used as historical controls. The Svetliza Reductibility Index
      consisted in dividing the real abdominal wall defect diameter by the larger
      intestinal loop to be fitted in such space. The EXIT-like procedure consists in
      planned cesarean section, fetal analgesia and return of the herniated viscera to
      the abdominal cavity before the baby can fill the intestines with air. No general
      anesthesia or uterine relaxation is needed. Exteriorized viscera reduction is
      performed while umbilical cord circulation is maintained. RESULTS: Four of the
      five cases were performed with the EXIT-like procedure. Successful complete
      closure was achieved in three infants. The other cases were planned deliveries at
      term and treated by construction of a Silo. The average time to return the
      viscera in EXIT-like Group was 5.0 minutes, and, in all cases, oximetry was
      maintained within normal ranges. In the perinatal period, there were significant
      statistical differences in ventilation days required (p = 0.0169), duration of
      parenteral nutrition (p=0.0104) and duration of enteral feed (p=0.0294).
      CONCLUSION: The Svetliza Reductibility Index and EXIT-like procedure could be new
      options to follow and treat gastroschisis, with significantly improved neonatal
      outcome in our unit. Further randomized studies are needed to evaluate this novel
      approach.

PMID- 29364361
TI  - Vascular endothelial growth factor gene variations as a risk predictor in disc
      degeneration.
AB  - OBJECTIVE: To evaluate the frequency of polymorphisms in the vascular endothelial
      growth factor (VEGF) gene, as well as to identify a potential risk haplotype
      among the polymorphic regions in this gene in patients with disc degeneration and
      in the Control Group. METHODS: This study analyzed a total of 217 individuals
      distributed into the Disc Degeneration and Control Groups. Peripheral blood was
      collected from all patients to detect VEGF gene polymorphisms identified by qPCR
      (rs699947, rs1570360, rs2010963, rs833061 and rs3025039). All patients presenting
      disc degeneration had the confirmation by nuclear magnetic resonance test and
      were rated according to disc degeneration level. RESULTS: All polymorphisms were
      in Hardy- Weinberg equilibrium (p>0.05) in the studied population. The genotypic
      frequency for Disc Degeneration and Control Group were rs699947 p = 0.475,
      rs1570360 p = 0.862, rs2010963 p = 0.823, rs833061 p=0.596 and rs3025039 p=0.230.
      In haplotype analysis, the compositions CAGGC (p=0.094) and CCGGC (p=0.054) stood
      out. CONCLUSION: The correlation between VEGF gene polymorphism as a risk
      predictor for disc degeneration was negative in the studied population. However,
      the VEGF gene has a large polymorphic region, and it is activated by various
      catabolic and metabolic factors in the disc degeneration process, which has not
      been fully elucidated.

PMID- 29364363
TI  - Association between active commuting and elevated blood pressure in adolescents.
AB  - OBJECTIVE: To analyze the association between active commuting and blood pressure
      in adolescents. METHODS: This is a cross-sectional study with high school
      students from public education network in the state of Pernambuco, Brazil. Data
      from 6039 students (14 to 19 years) were collected using a questionnaire.
      "Physically inactive" were considered those who reported not to walk or ride a
      bicycle to and from school on any day of the past week, and/or those who,
      regardless of the weekly frequency of practice this type of activity, reported
      the duration of commuting to school was less than 20 minutes (round trip). The
      high blood pressure was obtained by Omron HEM 742 equipment. Adolescents with
      high blood pressure were defined as those with higher blood pressure or equal to
      the 95th percentile for age, sex and height. Regression logistic analyses were
      used to assess the association between active commuting and high blood pressure,
      considering adjustments for the following confounders: sex, age, overweight,
      total physical activity, socioeconomic level, place of residence. RESULTS: The
      prevalence of high blood pressure was 7.3%, and 79.3% were considered
      insufficiently active in commuting. There was an association between high blood
      pressure and active commuting only among those living in rural areas (OR = 6.498;
      95% CI = 1.513-27.900), and the same was not observed among those living in urban
      areas (OR = 1.113; 95% CI = 0.812-1.526). CONCLUSION: Active commuting can be
      considered a protective factor for high blood pressure in adolescents living in
      rural areas.

PMID- 29364362
TI  - Do not attempt resuscitation orders at the emergency department of a teaching
      hospital.
AB  - OBJECTIVE: To identify factors associated with not attempting resuscitation.
      METHODS: A cross-sectional study conducted at the emergency department of a
      teaching hospital. The sample consisted of 285 patients; in that, 216 were
      submitted to cardiopulmonary resuscitation and 69 were not. The data were
      collected by means of the in-hospital Utstein Style. To compare resuscitation
      attempts with variables of interest we used the chi2 test, likelihood ratio,
      Fisher exact test, and analysis of variance (p<0.05). RESULTS: No cardiopulmonary
      resuscitation was considered unjustifiable in 56.5% of cases; in that, 37.7% did
      not want resuscitation and 5.8% were found dead. Of all patients, 22.4% had
      suffered a previous cardiac arrest, 49.1% were independent for Activities of
      Daily Living, 89.8% had positive past medical/surgical history; 63.8% were
      conscious, 69.8% were breathing and 74.4% had a pulse upon admission. Most events
      (76.4%) happened at the hospital, the presumed cause was respiratory failure in
      28.7% and, in 48.4%, electric activity without pulse was the initial rhythm. The
      most frequent cause of death was infection. The factors that influenced non
      resuscitation were advanced age, history of neoplasm and the initial arrest
      rhythm was asystole. CONCLUSION: Advanced age, past history of neoplasia and
      asystole as initial rhythm were factors that significantly influenced the non
      performance of resuscitation. Greater clarity when making the decision to
      resuscitate patients can positively affect the quality of life of survivors.

PMID- 29364364
TI  - Emergency Severity Index: accuracy in risk classification.
AB  - OBJECTIVE: To verify agreement between estimative of predicted resources using
      the adapted Emergency Severity Index and the real amount of resources used by
      patients. To analyze the variables number of years since graduation, years of
      work experience and years of experience in emergency services especially with
      accurate anticipation of resources need. METHODS: This retrospective analytical
      study with a quantitative approach included 538 medical records of patients
      assisted by 11 triage nurses. Data collected were related to assistances carried
      out from December 2012 to February 2013. RESULTS: There was no significant
      association between the adequacy of the number of resources used, based on
      Emergency Severity Index score, number of years since graduation, year of work
      experience or years of experience in emergency services. Kappa agreement
      coefficient (0.34) showed that agreement was low between predicted and real used
      number of resources. CONCLUSION: Nurses' accuracy index to predict resources for
      patients care from emergency room using the adapted Emergency Severity Index was
      lower than results reported in the studies in the literature that used the
      original scale. There was low agreement of diagnostic exams predicted by nurses
      and those really performed. There was no association among correct prediction of
      resources needed, number of years since graduation, years of experience in
      emergency services and years of work experience in the unit where the study was
      done.

PMID- 29364365
TI  - Self-perceived quality of health and satisfaction by elderly seen by the Family
      Health Strategy team.
AB  - OBJECTIVE: To verify the profile of elderly followed up by Family Health Strategy
      teams and the influence of self-reported chronic diseases on demographic
      variables, describing self-perception and satisfaction with quality of health.
      METHODS: This is a cross-sectional population- based study carried out with 301
      elderly residents in two areas of a city in southern Brazil. Data were collected
      through a questionnaire based on the Health, Well-Being, and Aging Study adapted
      by researchers, and a playful scale to assess satisfaction with health. For the
      statistical analysis, the chi2 test was used (p<0.05). RESULTS: Regarding
      cognitive assessment, the majority was classified as independent (86.4%), not
      requiring caregiver assistance to answer the questionnaire. The population was
      predominantly female (55.8%), White (64.8%), married (51.2%), and catholic
      (82.1%). A total of 47.5% considered their current health status as regular.
      Regarding satisfaction with health, 72.4% were happy, even reporting having at
      least one chronic health problem (58.5%). CONCLUSION: The presence of chronic
      diseases was reported by most respondents, and the practice of self-medication is
      significantly more frequent among the aged. Nevertheless, the degree of
      satisfaction with their health status was predominantly positive, both related to
      the previous year and compared to others of the same age.

PMID- 29364366
TI  - Urinary beta-trace protein gene expression analysis in type 2 diabetes mellitus
      patients.
AB  - OBJECTIVE: To evaluate the gene expression of beta-trace protein in urine of
      diabetic patients, with no reduction in glomerular filtration rate, which was
      defined as below 60mL/min/1.73m2. METHODS: Type 2 diabetes mellitus patients were
      recruited, and a group of non-diabetic individuals served as control. Beta-trace
      protein gene expression was analyzed by quantitative PCR. Blood samples were
      collected to establish glucose levels and baseline kidney function. Accuracy was
      analyzed using ROC curves. RESULTS: Ninety type 2 diabetes mellitus patients and
      20 non-diabetic individuals were recruited. The area under the curve was 0.601,
      sensitivity of 20% and specificity of 89.47%. Among diabetic participants, 18%
      showed an expression above the cutoff point. CONCLUSION: These results of
      accuracy of beta-trace protein gene expression in urine of diabetic patients are
      promising, although they did not achieve a higher area under the curve level.

PMID- 29364367
TI  - New therapeutic option in genitourinary syndrome of menopause: pilot study using
      microablative fractional radiofrequency.
AB  - OBJECTIVE: To evaluate the clinical response of patients with symptoms of
      genitourinary syndrome of menopause after application of microablative fractional
      radiofrequency in the vagina and vaginal introitus. METHODS: Fourteen patients
      with symptoms of genitourinary syndrome of menopause underwent three applications
      of microablative fractional radiofrequency with a 30-day interval, using the
      Wavetronic 6000HF-FRAXX device and a fractional vaginal electrode. The
      questionnaires World Health Organization Quality of Life (for quality of life
      evaluation), Female Sexual Function Index and Quality of Life Adapted
      Questionnaire in the Domain of Sexual Satisfaction (for sexual function and
      satisfaction evaluation) were administered before and after the applications (30
      to 60 days after the last procedure), in addition to the satisfaction
      questionnaire after procedure. RESULTS: There was an increase in almost all
      dimensions on average in quality of life, with statistical significance only in
      the health domain. There was a significant improvement in the sexual domains in
      almost all dimensions. All patients stopped using lubricant during intercourse
      after treatment. In the satisfaction questionnaire after treatment, we observed
      that the vast majority felt cured or much better (29% and 64%, respectively,
      total of 92.6%) and were very satisfied or satisfied (43 and 57%, respectively,
      total of 100%). The only patient who reported little improvement had an 18-year
      postmenopausal history and was treatment naive. CONCLUSION: Microablative
      fractional radiofrequency was effective in treating symptoms of vaginal dryness
      and dyspareunia, and eliminated the use of vaginal lubricant during the period
      observed. Since this is a pilot study with a small number of patients, further
      studies are required to corroborate our findings and evaluate the long-term
      effects of microablative fractional radiofrequency on the vaginal tissue.

PMID- 29364368
TI  - Initial experience with single-port robotic hysterectomy.
AB  - OBJECTIVE: This article presents the first series of robotic single-port
      hysterectomy cases performed at a hospital in Brazil. METHODS: From November 2014
      to October 2016, 11 patients were indicated to undergo, and nine of them were
      submitted to single-port hysterectomy using da Vinci Single-Site(r) platform.
      However, in two patients, due to multiple previous abdominal surgeries, large
      uterine volume, and/or a uterus with no mobility, a pneumoperitoneum was
      performed with a Verres needle, and the pelvic cavity was assessed using a 5mm
      optics endoscope. In these cases, single-port surgery was not recommended;
      therefore, multiportal robotic access was chosen, and no intercurrent events were
      reported. Nine single-port cases were operated on by the same surgeon at Hospital
      Israelita Albert Einstein. Patient data analyzed included age, body mass index,
      previous surgeries, and clinical diagnosis. Surgical data included operative
      time, skin incision, report of intraoperative complications, need for conversion
      to laparotomy, need for transfer to intensive care unit, need for blood
      transfusion, inadvertent injury to other organs, length of hospital stay, and
      death. RESULTS: All cases were completed with da Vinci Single-Site(r) system,
      with no intercurrent events. Four patients presented with adenomyosis as the
      surgical indication, two had uterine myoma, one endometrial cancer, one
      endometrial polyp, and one desquamative inflammatory vaginitis. The mean age of
      patients was 44 years (range, 40 to 54 years), and body mass index varied between
      23.4 and 33.2kg/m2 (mean 26.4). No complications occurred in any of the cases,
      such as intestinal or bladder injury, bleeding, or the need for a second surgery.
      All nine procedures were completed with the robotic single-port access, and no
      patient required a blood transfusion. CONCLUSION: Although this study merely
      presented an initial series of patients submitted to robotic single-port surgery,
      it demonstrated that the method is feasible and safe, suggesting the possible use
      of this technique in elective hysterectomy and other gynecological procedures in
      the future, as described in large reference centers of advanced surgery
      worldwide. Specifically, in gynecological practice, existing evidence on the use
      of robot-assisted, single-port surgery seems promising, and although it is not
      indicated in all cases, it should be considered as a surgical option.
      Nonetheless, further randomized and controlled clinical studies are necessary to
      establish the preeminence of robot-assisted, single-port surgery versus single
      incision and conventional laparoscopy.

PMID- 29364369
TI  - Regulation of adiposity by mTORC1.
AB  - Obesity is characterized by an excessive increase in the adipose tissue mass, and
      is associated with higher incidence of several chronic metabolic diseases, such
      as type 2 diabetes. Therefore, its increasing prevalence is a public health
      concern, and it is important to better understand its etiology to develop new
      therapeutic strategies. Evidence accumulated over the years indicates that
      obesity is associated with a marked activation in adipose tissue of the
      mechanistic target of rapamycin complex 1 (mTORC1), a signaling pathway that
      controls lipid metabolism, and adipocyte formation and maintenance. Curiously,
      mTORC1 is also involved in the control of nonshivering thermogenesis and
      recruitment as well as browning of white adipose tissue. In this review, we
      explored mTORC1 functions in adipocytes and presented evidence, suggesting that
      mTORC1 may either increase or reduce adiposity, depending on the conditions and
      activation levels.

PMID- 29364370
TI  - Munchausen syndrome and Munchausen syndrome by proxy: a narrative review.
AB  - The Munchausen syndrome and Munchausen syndrome by proxy are factitious disorders
      characterized by fabrication or induction of signs or symptoms of a disease, as
      well as alteration of laboratory tests. People with this syndrome pretend that
      they are sick and tend to seek treatment, without secondary gains, at different
      care facilities. Both syndromes are well-recognized conditions described in the
      literature since 1951. They are frequently observed by health teams in clinics,
      hospital wards and emergency rooms. We performed a narrative, nonsystematic
      review of the literature, including case reports, case series, and review
      articles indexed in MEDLINE/PubMed from 1951 to 2015. Each study was reviewed by
      two psychiatry specialists, who selected, by consensus, the studies to be
      included in the review. Although Munchausen syndrome was first described more
      than 60 years ago, most of studies in the literature about it are case reports
      and literature reviews. Literature lacks more consistent studies about this
      syndrome epidemiology, therapeutic management and prognosis. Undoubtedly, these
      conditions generate high costs and unnecessary procedures in health care
      facilities, and their underdiagnose might be for lack of health professional's
      knowledge about them, and to the high incidence of countertransference to these
      patients and to others, who are exposed to high morbidity and mortality, is due
      to symptoms imposed on self or on others.

PMID- 29364371
TI  - Comment to: II Brazilian Consensus on the use of human immunoglobulin in patients
      with primary immunodeficiencies. einstein (Sao Paulo). 2017;15(1):1-16.

PMID- 29364372
TI  - A new way to communicate science in the era of Big Data and citizen science.

PMID- 29364373
TI  - Public health policies and scientific evidence.

PMID- 29364374
TI  - Thank you very much!

PMID- 29364375
TI  - An interview with Mario Polo.

PMID- 29364376
TI  - "Maxillary lateral incisor partial anodontia sequence": a clinical entity with
      epigenetic origin.
AB  - The relationship between maxillary lateral incisor anodontia and the palatal
      displacement of unerupted maxillary canines cannot be considered as a multiple
      tooth abnormality with defined genetic etiology in order to be regarded as a
      "syndrome". Neither were the involved genes identified and located in the human
      genome, nor was it presumed on which chromosome the responsible gene would be
      located. The palatal maxillary canine displacement in cases of partial anodontia
      of the maxillary lateral incisor is potentially associated with environmental
      changes caused by its absence in its place of formation and eruption, which would
      characterize an epigenetic etiology. The lack of the maxillary lateral incisor in
      the canine region means removing one of the reference guides for the eruptive
      trajectory of the maxillary canine, which would therefore, not erupt and /or
      impact on the palate. Consequently, and in sequence, it would lead to
      malocclusion, maxillary atresia, transposition, prolonged retention of the
      deciduous canine and resorption in the neighboring teeth. Thus, we can say that
      we are dealing with a set of anomalies and multiple sequential changes known as
      sequential development anomalies or, simply, sequence. Once the epigenetics and
      sequential condition is accepted for this clinical picture, it could be called
      "Maxillary Lateral Incisor Partial Anodontia Sequence."

PMID- 29364377
TI  - Comparison of airway dimensions in skeletal Class I malocclusion subjects with
      different vertical facial patterns.
AB  - OBJECTIVE: The aim of this study was to compare upper airway widths among
      skeletal Class I malocclusion subjects with different vertical facial patterns.
      METHODS: The sample included a total of 99 lateral cephalograms of post pubertal
      individuals (18.19 +/- 1.76 years old). The vertical facial pattern was
      determined by the Vert index. The McNamara method was used to quantify upper
      airway widths. ANOVA test and Student's t test for independent groups were used,
      when normal distribution was not supported Kruskal-Wallis test and U-Mann-Whitney
      test were used. A multiple linear regression analysis was also performed.
      RESULTS: Statistically significant differences in several nasopharyngeal widths
      were found among the distinct vertical facial patterns. Subjects with
      brachyfacial pattern presented larger nasopharyngeal widths than subjects with
      mesofacial (p= 0.030) or dolichofacial (p= 0.034) patterns. The larger the Vert
      value, the larger the nasopharyngeal widths (R2= 26.2%, p< 0.001). At the level
      of oropharynx no statistically significant differences were found. CONCLUSION: It
      was concluded that nasopharyngeal linear anteroposterior widths in Class I
      malocclusion brachyfacial are larger than in mesofacial and dolichofacial
      individuals. The Vert index only explained 25% of the total variability. No
      correlation was found for the oropharyngeal widths.

PMID- 29364378
TI  - Plaque index and gingival index during rapid maxillary expansion of patients with
      unilateral cleft lip and palate.
AB  - OBJECTIVE: To assess, during rapid maxillary expansion, the plaque index (PI) and
      the gingival index (GI) of patients with unilateral cleft lip and palate(UCLP)
      using Hyrax (HX) or inverted mini-Hyrax (IMHX) rapid maxillary expanders (RME)
      considering patients' sex and age. METHODS: PI (Quigley Index modified by Turesky
      et al) and GI (Loe and Silness) of 28 UCLP (11 females; 17 males: aged 8 to 15
      years) submitted to daily RME activation were assessed before (T0) and 7 (T1), 28
      (T2) and 90 (T3) days after activation. Log-linear models and Bonferroni
      correction were performed to analyze possible differences in PI and GI between
      RME, sexes or age groups over time. RESULTS: Intra-group comparison revealed
      significant increases in PI of patients using HX (T0 < T2), IMHX (T0 < T3; T1<
      T3), males (T0 < T1; T0 < T2; T0 < T3) or aged 12-15 years (T0 < T1; T0 < T2; T0
      < T3), and in GI of patients using IMHX (T0 < T3; T1 < T3), females (T1 < T3; T2
      < T3) or aged 12-15 years (T0 < T3; T2 < T3). One inter-group difference in GI
      according to patients' age (8-11 < 12-15; T1) was observed. CONCLUSIONS: Since a
      single difference between groups was encountered, the results of this study
      indicated that PI and GI during maxillary expansion were similar between HX and
      IMHX, sexes and the analyzed age groups. Therefore, orthodontists can use these
      RME in UCLP patients according to the patient's necessity or their preferences.

PMID- 29364379
TI  - Efficiency of compensatory orthodontic treatment of mild Class III malocclusion
      with two different bracket systems.
AB  - OBJECTIVE: The purpose of this study was to assess the efficiency of compensatory
      orthodontic treatment of patients with mild Class III malocclusion with two
      preadjusted bracket systems. METHOD: Fifty-six matched patients consecutively
      treated for mild Class III malocclusion through compensatory dentoalveolar
      movements were retrospectively evaluated after analysis of orthodontic records.
      The sample was divided into two groups according to the brackets used: Group 1 =
      non-Class III compensated preadjusted brackets, Roth prescription (n = 28); Group
      2 = compensated Class III preadjusted brackets, Capelozza III prescription (n =
      28). Cephalometric analysis, number of appointments and missed appointments,
      months using Class III elastics, and bond/band failures were considered.
      Treatment time, Peer Assessment Rating (PAR) index at the beginning (PAR T1) and
      end of treatment (PAR T2) were used to calculate treatment efficiency. Comparison
      was performed using a MANOVA at p< 0.05. RESULTS: Missed appointments, bond or
      band failures, number of months using the Class III intermaxillary elastics, and
      cephalometric measurements showed no statistically significant difference (p>
      0.05) between groups. Patients treated with Roth brackets had a treatment time 7
      months longer (p= 0.01). Significant improvement in the patient's occlusion (PAR
      T2-T1) was observed for both groups without difference (p= 0.22). CONCLUSIONS:
      Orthodontic brackets designed for compensation of mild Class III malocclusions
      appear to be more efficient than non-compensated straight-wire prescription
      brackets. Treatment time for Class III patients treated with brackets designed
      for compensation was shorter than with Roth prescription and no difference in the
      quality of the occlusal outcome was observed. A prospective randomized study is
      suggested to provide a deeper look into this subject.

PMID- 29364380
TI  - Distances between mandibular posterior teeth and the WALA ridge in Peruvians with
      normal occlusion.
AB  - OBJECTIVE: The purposes of this investigation were to determine the horizontal
      distances between the mandibular posterior teeth and the WALA ridge in a sample
      of Peruvians with normal occlusion and to compare them by tooth type, sex, arch
      side, and age groups. METHODS: 65 dental casts of subjects with normal occlusion
      were collected. Posterior teeth, except for third molars, were evaluated. The
      horizontal distances between the occluso-gingival midpoints of the buccal
      surfaces (FA points) of each tooth and the WALA ridge were measured using a
      modified digital caliper. The values between each different tooth type within the
      sample were compared using the ANOVA and Scheffe tests, while comparisons by sex,
      arch side and age groups, using the Student's t-test. RESULTS: The mean distances
      in the sample was 0.96 mm for first premolars, 1.45 mm for second premolars, 2.12
      mm for first molars and 2.55 mm for second molars. Statistically significant
      differences between each of the four tooth types were found. There were no
      significant differences found between sex, arch side and age groups. CONCLUSION:
      The horizontal distances between the mandibular posterior teeth and the WALA
      ridge increased progressively from the first premolars to the second molars in
      Peruvians with normal occlusion. The WALA ridge was a good landmark to evaluate
      the positions of posterior teeth in Peruvians with normal occlusion.

PMID- 29364381
TI  - Stability of beta-titanium T-loop springs preactivated by gradual curvature.
AB  - OBJECTIVE: Evaluate changes in the force system of T-Loop Springs (TLS)
      preactivated by curvature, due to stress relaxation. METHODS: Ninety TLSs
      measuring 6 x 10 mm, produced out with 0.017 x 0.025-in TMA(r) wire and
      preactived by gradual curvature, were randomly distributed into nine groups
      according to time point of evaluation. Group 1 was tested immediately after
      spring preactivation and stress relief, by trial activation. The other eight
      groups were tested after 24, 48 and 72 hours, 1, 2, 4, 8 and 12 weeks,
      respectively. Using a moment transducer coupled to a digital extensometer
      indicator adapted to a universal testing machine, the amount of horizontal force,
      moment and moment-to-force ratios were recorded at every 0.5 mm of deactivation
      from 5 mm of the initial activation, in an interbracket distance of 23 mm.
      RESULTS: The horizontal forces decreased gradually among the groups (p< 0.001)
      and the moments showed a significant and slow decrease over time among the groups
      (p< 0.001). All groups produced similar M/F ratios (p= 0.532), with no influence
      of time. CONCLUSIONS: The TLSs preactivated by curvature suffered a gradual
      deformation over time, which affected the force system, specifically the moments,
      which affected the horizontal forces produced.

PMID- 29364382
TI  - Digital models: How can dental arch form be verified chairside?
AB  - INTRODUCTION: Plaster dental casts are routinely used during clinical practice to
      access maxillary dental arch form and assist on fabrication of individualized
      orthodontic archwires. Recently introduced, digital model technology may offer a
      limitation for the obtainment of a dental physical record. In this context, a
      tool for dental arch form assessment for chairside use is necessary when
      employing digital models. In this regard, paper print of the dental arch seems
      thus to be useful. METHODS: In the present study, 37 lower arch models were used.
      Intercanine and intermolar widths and dental arch length measurements were
      performed and compared using plaster dental casts, digital models and paper print
      image of the models. Ortho Insight 3D scanner was employed for model
      digitalization. RESULTS: No statistically significant differences were noted
      regarding the measurements performed on the plaster or digital models (p> 0.05).
      Paper print images, however, showed subestimated values for intercanine and
      intermolar widths and overestimated values for dental arch length. Despite being
      statistically significant (p< 0.001), the differences were considered clinically
      negligible. CONCLUSION: The present study suggests that paper print images
      obtained from digital models are clinically accurate and can be used as a tool
      for dental arch form assessment for fabrication of individualized orthodontic
      archwires.

PMID- 29364383
TI  - Nonsurgical treatment for a severe anterior and lateral open bite and multiple
      congenitally missing teeth: a case report with 4-year follow-up.
AB  - This case report describes the treatment of a severe anterior and lateral open
      bite combined with multiple congenitally missing teeth. A 10-year-old girl
      presented with an open gonial angle, absence of lip sealing, and soft tissue
      pogonion retrusion. She had an open bite of 8.5 mm, agenesis of the upper right
      and left lateral incisors and the upper left first premolar, and transverse
      maxillary deficiency. Nonsurgical treatment was planned aiming at controlling the
      vertical pattern, establishing the correct overbite, and closing the spaces on
      the upper arch, to provide satisfactory occlusion and facial and dental
      esthetics.

PMID- 29364384
TI  - Compensatory Class III malocclusion treatment associated with mandibular canine
      extractions.
AB  - Skeletal Class III malocclusions are ideally treated with orthodontic-surgical
      approaches. However, if there are no significant soft tissue implications and the
      patient does not want to undergo orthognatic surgery, other treatment options may
      be considered. The current case report describes a compensatory alternative for
      Class III malocclusion treatment, by means of mandibular canine extractions. This
      treatment alternative provided facial profile and occlusal improvement, which
      remains stable seven years posttreatment.

PMID- 29364386
TI  - Message from the new editors of Arquivos de Neuro-Psiquiatria.

PMID- 29364385
TI  - High-intensity laser application in Orthodontics.
AB  - INTRODUCTION: In dental practice, low-level laser therapy (LLLT) and high
      intensity laser therapy (HILT) are mainly used for dental surgery and
      biostimulation therapy. Within the Orthodontic specialty, while LLLT has been
      widely used to treat pain associated with orthodontic movement, accelerate bone
      regeneration after rapid maxillary expansion, and enhance orthodontic tooth
      movement, HILT, in turn, has been seen as an alternative for addressing soft
      tissue complications associated to orthodontic treatment. OBJECTIVE: The aim of
      this study is to discuss HILT applications in orthodontic treatment. METHODS:
      This study describes the use of HILT in surgical treatments such as gingivectomy,
      ulotomy, ulectomy, fiberotomy, labial and lingual frenectomies, as well as hard
      tissue and other dental restorative materials applications. CONCLUSION: Despite
      the many applications for lasers in Orthodontics, they are still underused by
      Brazilian practitioners. However, it is quite likely that this demand will
      increase over the next years - following the trend in the USA, where laser
      therapies are more widely used.

PMID- 29364387
TI  - Non-inflammatory cerebrospinal fluid delays the diagnosis and start of
      immunotherapy in anti-NMDAR encephalitis.
AB  - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of
      autoimmune encephalopathy that presents with a wide variety of symptoms,
      including neuropsychiatric manifestations. The authors' aim for this study was to
      analyze the results of paraclinical studies of patients with a diagnosis of anti
      NMDAR encephalitis and the association between symptom onset and diagnosis, and
      start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR
      encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients
      (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an
      inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The
      absence of pleocytosis or increased proteins in the CSF was associated with a
      longer time from symptom onset to diagnosis and treatment (p = 0.003). The
      authors conclude that noninflammatory CSF may delay the correct diagnosis and
      start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive
      clinical features, extensive studies including EEG are recommended.

PMID- 29364388
TI  - Multiple sclerosis risk perception and acceptance for Brazilian patients.
AB  - The perception of multiple sclerosis (MS) severity and risk associated with
      therapies might influence shared decision making in different countries. We
      investigated the perception of MS severity and factors associated with risk
      acceptance in Brazil in 96 patients with relapsing-remitting MS using a
      standardized questionnaire and compared this with two European cohorts. Multiple
      sclerosis was perceived as a very severe disease and the risk of developing
      progressive multifocal leukoencephalopathy due to natalizumab was seen as
      moderate to high. Seventy-six percent considered a risk of 1:1,000, or higher, an
      impediment for natalizumab use. Older age was the only variable associated with
      higher risk acceptance and our patients showed a more conservative profile than
      German and Spanish patients. Our patients perceived MS severity and progressive
      multifocal leukoencephalopathy risk similarly to elsewhere, but their willingness
      to take risks was more conservative. This should be considered when discussing
      therapeutic options and it might have an impact on guideline adaptations.

PMID- 29364389
TI  - Medical perception of stroke care conditions in Brazil.
AB  - Stroke is currently the second leading cause of death in Brazil. Neurologists'
      reports on the absence of adequate resources for stroke care are frequent;
      however, there are no objective data on this perception.To assess the perception
      of neurologists of stroke care conditions in Brazil. Neurologists from all over
      Brazil were surveyed by means of an anonymous questionnaire about the main
      shortcomings in stroke care, focusing particularly on physical structure and
      infrastructure (diagnostic methods, patient transport, availability of beds,
      multi-professional team). The main shortcomings are indicated: the worst
      conditions, among all items surveyed, were found in the public sector. In the
      private sector, conditions were better. Care conditions are worse in the public
      sector with regard to both infrastructure and human resources. Future public
      health policies for the prevention and treatment of stroke should be formulated,
      taking into consideration neurologists' perceptions.

PMID- 29364390
TI  - Anticoagulation in patients with cardiac manifestations of Chagas disease and
      cardioembolic ischemic stroke.
AB  - To describe anticoagulation characteristics in patients with cardiac
      complications from Chagas disease and compare participants with and without
      cardioembolic ischemic stroke (CIS). A retrospective cohort of patients with
      Chagas disease, using anticoagulation, conducted from January 2011 to December
      2014. Forty-two patients with Chagas disease who were using anticoagulation were
      studied (age 62.9+/-12.4 years), 59.5% female and 47.6% with previous CIS, 78.6%
      with non-valvular atrial fibrillation and 69.7% with dilated cardiomyopathy.
      Warfarin was used in 78.6% of patients and dabigatran (at different times) in
      38%. In the warfarin group, those with CIS had more medical appointments per
      person-years of follow-up (11.7 vs 7.9), a higher proportion of international
      normalized ratios within the therapeutic range (57% vs 42% medical appointments,
      p = 0.025) and an eight times higher frequency of minor bleeding (0.64 vs 0.07
      medical appointments). Patients with Chagas disease and previous CIS had better
      control of INR with a higher frequency of minor bleeding.

PMID- 29364391
TI  - A Brazilian-Portuguese version of the Kinesthetic and Visual Motor Imagery
      Questionnaire.
AB  - Motor imagery has emerged as a potential rehabilitation tool in stroke. The goals
      of this study were: 1) to develop a translated and culturally-adapted Brazilian
      Portugese version of the Kinesthetic and Visual Motor Imagery Questionnaire
      (KVIQ20-P); 2) to evaluate the psychometric characteristics of the scale in a
      group of patients with stroke and in an age-matched control group; 3) to compare
      the KVIQ20 performance between the two groups. Test-retest, inter-rater
      reliabilities, and internal consistencies were evaluated in 40 patients with
      stroke and 31 healthy participants. In the stroke group, ICC confidence intervals
      showed excellent test-retest and inter-rater reliabilities. Cronbach's alpha also
      indicated excellent internal consistency. Results for controls were comparable to
      those obtained in persons with stroke. The excellent psychometric properties of
      the KVIQ20-P should be considered during the design of studies of motor imagery
      interventions for stroke rehabilitation.

PMID- 29364392
TI  - Thymoquinone reverses learning and memory impairments and brain tissue oxidative
      damage in hypothyroid juvenile rats.
AB  - In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced
      memory impairment was investigated in juvenile rats. The rats were grouped into
      control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in
      the Morris water maze test and decreased delay in entering the dark compartment
      in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased
      latency time in the Morris water maze test and increased delay in entering the
      dark compartment in a passive avoidance test. The PTU also increased
      malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol
      content and superoxide dismutase and catalase activities and serum T4 level. Both
      doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain
      while enhanced the thiol content and superoxide dismutase and catalase activities
      and serum T4 level. The results of the present study showed that TQ protected
      against PTU-induced memory impairments in rats.

PMID- 29364394
TI  - Arquivos de Neuro-Psiquiatria: 75 years.
AB  - This year marks the 75th year of publication of Arquivos de Neuro-Psiquiatria
      (ANP), the official journal of the Brazilian Academy of Neurology and one of the
      most important neuroscience journals in Latin America. ANP was initially edited
      by Oswaldo Lange, its founder, and subsequently by Antonio Spina-Franca Netto
      and, in recent years, by Jose Antonio Livramento and Luis dos Ramos Machado.

PMID- 29364393
TI  - Autoimmune encephalitis: a review of diagnosis and treatment.
AB  - Autoimmune encephalitis (AIE) is one of the most common causes of noninfectious
      encephalitis. It can be triggered by tumors, infections, or it may be
      cryptogenic. The neurological manifestations can be either acute or subacute and
      usually develop within six weeks. There are a variety of clinical manifestations
      including behavioral and psychiatric symptoms, autonomic disturbances, movement
      disorders, and seizures. We reviewed common forms of AIE and discuss their
      diagnostic approach and treatment.

PMID- 29364395
TI  - Searching for neurological diseases in the Julio-Claudian dynasty of the Roman
      Empire.
AB  - The gens Julia was one of the oldest families in ancient Rome, whose members
      reached the highest positions of power. They made history because Julius Caesar,
      perpetual dictator, great-uncle of the first emperor, Augustus, passed his name
      on to the Julio-Claudian dynasty with the emperors Tiberius, Caligula, Claudius
      and Nero. Descriptions of the diseases of these emperors and some of his family
      members may indicate diagnoses such as epilepsy, dystonia, dementia,
      encephalitis, neurosyphilis, peripheral neuropathies, dyslexia, migraine and
      sleep disorders. In the historical context of ancient Rome, the possibility of
      infectious diseases related to the libertine way of life is quite large. However,
      there is a possibility that some of these diseases occurred from genetic
      transmission.

PMID- 29364396
TI  - "Acute Dupuytren's contracture": the answer is not always in your hands.

PMID- 29364397
TI  - Proximal limb weakness and amyotrophy in a man with silicosis.

PMID- 29364398
TI  - Delayed hemiparkinsonism after closed head injury.

PMID- 29364399
TI  - Rapidly progressive subacute motor neuronopathy disclosing type B2 thymoma.

PMID- 29364400
TI  - Incidence of Guillain-Barre syndrome among Zika virus infected cases: a report
      from Thailand.

PMID- 29364401
TI  - [Toward eradication of anemia in Peru].

PMID- 29364402
TI  - [Barriers and Facilitators of Micronutrient Powder Supplementation: Maternal
      Perceptions and Dynamics of Health Services].
AB  - OBJECTIVES: To explore the barriers and facilitators of micronutrient powder
      (MNP) supplementation to mothers of children aged 6 to 35 months living in the
      Peruvian cities of Tacna, Loreto, Puno, and Lima. MATERIALS AND METHODS: This
      qualitative exploratory study with a grounded theory approach was conducted in
      the Peruvian cities of Lima, Tacna, Loreto, and Puno in 2014. In-depth interviews
      were conducted with mothers of children younger than 3 years, and observations in
      health care facilities (HCFs) were made to determine the barriers and
      facilitators of MNP supplementation. RESULTS: The barriers identified at the
      health care level were limited access to HCFs, negative rumors regarding the MNP
      in the clinics, and poor care by health personnel. The barrier at the product
      (MNP) level was the lack of knowledge about the supplement, including taste and
      side effects. The barrier at the maternal level was lack of time, neglect,
      difficulties in preparing the MNP, and opposition to the use of the MNP by the
      husband. The main facilitators were receiving information from health personnel
      regarding child improvement, mother's perception of child's improvement, and
      positive testimonies about the effectiveness of the MNP from relatives and
      neighbors. CONCLUSIONS: Barriers regarding MNP use at the health care system
      level and those associated with the behavior mothers and family/community, which
      prevent children from consuming the MNP supplement daily, need to be addressed
      through the development of strategies. Strategies must be developed to overcome
      the barriers related to the health care system, the MNP, and the behavior of
      children, mothers, and family/community because these barriers prevent children
      from consuming the MNP daily.

PMID- 29364403
TI  - [Effect of Rest Pauses Combined with Information Leaflets on the Decrease in
      Musculoskeletal Pain in Administrative Workers].
AB  - OBJECTIVES: To assess the effect of work pauses combined with information
      leaflets on the reduction of musculoskeletal pain in administrative workers of a
      public institution in Lima, Peru. MATERIALS AND METHODS: This quasi-experimental
      study was conducted in two offices of a public institution and included an
      intervention group and a non-randomized control group. The intervention group (n
      = 135) was provided with information leaflets once a week, in addition to a
      program of rest pauses consisting of breathing exercises, stretching, and
      encouragement. The control group (n = 127) received information leaflets once a
      week. To assess outcomes, the rate and intensity of musculoskeletal pain over the
      previous 7 days were measured. RESULTS: The mean age of participants was 38
      years. The most affected body regions were the neck and lumbar spine. In the
      intervention group, the rate of musculoskeletal pain was reduced by 20% in the
      neck (p<0.001) and 17% in the lumbar spine (p<0.001) over the previous 7 days. In
      the control group, the rate of musculoskeletal pain was decreased only in the
      lumbar spine (p=0.029). The intervention group reported less pain in all
      evaluated body regions (p<0.05). CONCLUSIONS: Rest pauses combined with
      information leaflets resulted in decreased musculoskeletal pain in administrative
      workers, indicating that this strategy can be implemented in public and private
      institutions.

PMID- 29364404
TI  - [Prevention of Maternal-Child Transmission of HIV in Pregnant Women and Mothers
      of the Awajun and Wampis Communities in the Amazon Region of Peru].
AB  - OBJECTIVES: To identify the barriers that limit compliance with the prevention of
      mother-to-child transmission (PMTCT) of HIV measures in two indigenous
      communities of the Amazon region of Peru. MATERIALS AND METHODS: Qualitative
      study with a phenomenological approach. Semi-structured interviews were conducted
      with pregnant women and mothers of children younger than 1 year of the awajun and
      wampis indigenous communities diagnosed with HIV in the period 2014-2015.
      RESULTS: The study sample included 15 of 29 eligible women and 87% were Awajun.
      Limitations and possible negative effects were observed in cases in which
      sanitary measures for PMTCT were imposed. Considering their knowledge of
      diseases, including the presence of symptoms and disabilities, many women from
      these communities do not believe they are infected with HIV and consider the
      diagnosis a lie or relate the diagnosis to harm, and these beliefs limit their
      compliance with medical indications and decrease their trust in health services.
      In addition, the women believe that their children will inevitably be born sick
      and will die soon, and thus consider cesarean sections and child care a futile
      effort. Other factors influencing the successful implementation of PMTCT measures
      include language barriers, remoteness of health centers, and the fear of judgment
      and moral condemnation by the local community. CONCLUSIONS: PMTCT measures
      challenge the customs, values, and beliefs of pregnant women and mothers in the
      Awajun and Wampis indigenous communities, and thus these measures are not
      understood or accepted, jeopardizing the relationship of the mothers with health
      personnel. Therefore, cultural factors and interventions appropriate to this
      population must be better understood.

PMID- 29364406
TI  - [Epidemiological Clinical Characteristics of Acute Cardiac Insufficiency in a
      Tertiary Hospital in Lima, Peru].
AB  - The objective of this study was to describe the clinical and epidemiological
      characteristics of acute heart failure (AHF) in 1,075 patients from a hospital in
      Lima, Peru. The average patient age was 74 years and 55% of study subjects were
      men. Moreover, 39% of patients in the sample had AHF with low ejection fraction,
      15% had intermediate ejection fraction, and 46% had preserved ejection fraction.
      The most common comorbidities were hypertension (52.6%) and coronary disease
      (51%). Moreover, 29.2% of patients had previous hospitalizations due to AHF. The
      median hospital stay was 3 days. The rate of in- hospital mortality from all
      causes was 7.2%. Hospitalization was more common in elderly patients with
      multiple comorbidities. The low use of prescription drugs together with the high
      rate of previous hospitalizations may explain the high mortality rate reported in
      this study.

PMID- 29364405
TI  - [Antiurolithic Activity of the Ethanolic Extract of Ayacuchano Propolis in Rats].
AB  - OBJECTIVES: To determine the antiurolytic activity of the ethanolic extract of
      Ayacuchan propolis in a preventive model of urolithiasis in rats. MATERIALS AND
      METHODS: A total of 45 male Sprague-Dawley albino rats were studied. The
      antiurolithic effect was analyzed in five groups of six animals each: blank,
      control (treated with 1 mL of 5% ethylene glycol and 1 mL of 5% ammonium
      chloride), and three experimental groups (treated with the ethanol extract of
      propolis at a daily dose of 250, 350, and 500 mg/kg, respectively). The drugs
      were administered by orogastric cannulation for 16 days. The diuretic effect was
      evaluated in 15 rats distributed in five groups: blank, control (treated with
      furosemide at 20 mg/kg), and three experimental groups (treated with the ethanol
      extract of propolis at daily doses of 250, 350, and 500 mg/kg, respectively).
      Urinary pH, urinary density, and sedimentation of calcium oxalate were measured.
      The presence of kidney stones was evaluated by examination of hematoxylin-eosin
      stained histopathological sections under polarized light. RESULTS: The ethanolic
      extract of Ayacuchan propolis caused significant changes in the levels of uric
      acid, serum lactate dehydrogenase, pH, and urinary density in the three dose
      groups. The results of histological analysis indicated a lower presence of
      calcium oxalate crystals in kidney tubular cells in the group treated with 250
      mg/kg. The diuretic effect in the group treated with 250 mg/kg was higher than
      that in the control group. CONCLUSIONS: The ethanolic extract of Ayacuchan
      propolis demonstrated antiurolytic activity in a preventive rat model of
      urolithiasis.

PMID- 29364407
TI  - [Colonization by Enterococcal Strains Resistant to Vancomycin in Patients from a
      Hospital in Lima, Peru].
AB  - This cross-sectional study was conducted from November to December of 2013 at the
      Cayetano Heredia National Hospital in Lima, Peru, to determine the rate of
      infection with vancomycin-resistant enterococcus (VRE), the resistance genotype,
      and associated factors. The rate of infection with VRE was 6.2% (95% confidence
      interval [CI]: 1.67-10.73) and the resistance genotype isolated from all strains
      was the vanA gene. The factors associated with colonization with VRE were
      previous hospitalizations (p = 0.001) and the use of third-generation
      cephalosporins (p = 0.016). In conclusion, perianal colonization with VRE is
      present in many hospital services. Moreover, the vanA gene may cause resistance
      to vancomycin and promote the development of vancomycin-resistant Staphylococcus
      aureus. Therefore, infection control measures should be adopted to prevent the
      dissemination of this bacterial strain in hospital settings.

PMID- 29364408
TI  - [Concentration of Malondialdehyde in Subjects Living at High Altitudes:
      Exploratory Study].
AB  - The objective of this study was to determine the levels of malondialdehyde (MDA),
      an oxidative stress biomarker, in individuals living at high altitudes (3500-4200
      m). This exploratory study evaluated 91 subjects from La Paz and El Alto using a
      questionnaire and clinical examination. MDA levels were measured using a
      colorimetric technique. Measures of central tendency, dispersion, and percentages
      were used to describe data, and the Mann-Whitney test and Kruskal-Wallis test
      were used to assess differences between the sexes, age groups, and altitudes. The
      median concentration of MDA was 4.1 MUmol/L (RIC 2.4-5.4) and the highest
      concentration of MDA was found in individuals older than 40 years. The average
      MDA levels were higher than those found at sea level, a result we believe is due
      to the effect of hypoxia. However, there were no differences in the MDA levels
      between the sexes or age groups.

PMID- 29364409
TI  - [Biomarkers of Metabolism and Iron Nutrition].
AB  - Iron deficiency anemia is the most common nutritional deficiency worldwide, and
      the most susceptible groups are infants, preschoolers, women of childbearing age,
      and pregnant women. It is therefore essential to understand the mechanisms of
      regulation of iron uptake, transport, and absorption at the cellular level,
      particularly in enterocytes, and to identify blood biomarkers that allow the
      evaluation of iron status. This review describes how iron absorption is regulated
      by intestinal epithelial cells, the main proteins involved (iron transporters,
      oxidoreductases, storage proteins), and the main blood biomarkers of iron
      metabolism.

PMID- 29364410
TI  - [Recommendations for Interventions with Iron Supplements: Lessons Learned in a
      Community Trial in Four Regions of Peru].
AB  - Iron supplementation programs, despite evidence of their effectiveness in
      controlled conditions, are not effective as largescale interventions in health
      services because of the necessary involvement during execution of a series of
      processes that, when not fulfilled, limit the implementation of the program. In
      many cases, the lack of impact of interventions to provide iron supplements is
      the result of failures or deviations from execution rather than flaws in the
      intervention design (theory of change) or intervention strategy. The objective of
      this study was to share the lessons learned in the execution of a community trial
      in 2015 to improve adherence to micronutrient powder supplementation in children
      younger than 3 years in four regions of Peru, as well as to provide
      recommendations on iron supplementation in children to help close gaps in the
      design and execution of public policies.

PMID- 29364411
TI  - [Prevention, Diagnosis, and Treatment of Pediatric Infections During Natural
      Disasters].
AB  - The objective of this review was to provide guidelines regarding the diagnosis,
      treatment, and prevention of the most common infectious diseases in children
      during natural disasters, including floods such as those that occurred in the
      summer of 2017 in Peru. This instrument should be used by physicians and health
      personnel working in primary health care. The management of diarrheal,
      respiratory, skin, and eye diseases, vector-transmitted diseases such as dengue,
      chikungunya, and Zika, and zoonoses such as leptospirosis is discussed. Emphasis
      is placed on the essential aspects of health education for the population,
      particularly preventive health, including the use of potable water,
      breastfeeding, immunization, hand washing, and vector control.

PMID- 29364412
TI  - [Use of Deliberative Dialogues for the Formulation of Recommendations for
      Clinical Practice Guidelines].
AB  - This study reports the experience obtained by the National Institute of Health of
      Peru in the use of deliberative dialogues for the formulation of recommendations
      as one of the stages of the process of adaptation of evidence-based clinical
      practice guidelines using the Grading of Recommendations, Assessment,
      Development, and Evaluations (GRADE) system. Using a multidisciplinary approach,
      this study describes: 1. the public health problems addressed in the dialogues;
      2. the role of the involved parties; 3. the parameters that were considered
      before and during the discussions; 4. the challenges for optimizing these
      dialogues and stimulating the interaction between scientific evidence and the
      added value provided by the involved parties through their experiences,
      perspectives, and knowledge for the development of recommendations in health.

PMID- 29364413
TI  - [Post-Traumatic Stress Disorder in a Population Affected by Floods Caused by El
      Nino in Peru].

PMID- 29364414
TI  - [Rights and Duties of Citizens: Health Users and Health Workers].

PMID- 29364415
TI  - [Childhood anemia: challenges and opportunities for 2021].

PMID- 29364416
TI  - [Contextualization of sexual initiation and individual barriers to the use of
      contraceptives by adolescents of Lima, Huamanga, and Iquitos].
AB  - OBJECTIVES. : To contextualize sexual initiation and barriers to the use of
      contraceptives by adolescents as well as the acquisition of adequate knowledge
      regarding contraception and sexually transmitted diseases. MATERIALS AND METHODS.
      : This quantitative and qualitative study evaluated adolescents living in three
      cities with high pregnancy rates in Peru: Iquitos, Huamanga, and Lima. Subjects
      were invited to participate in the study via Facebook. Questionnaires were then
      used to select adolescents who met the inclusion criteria, and interviews were
      conducted to obtain detailed data regarding the study topic. RESULTS. : A total
      of 33 women and 23 men aged 18 to 19 years participated in the study. The age of
      onset of sexual activity ranged from 14 to 16 years; the main reasons for sexual
      initiation were sexual desire among men and pressure from the partner among
      women; in most cases, the sexual partner was an occasional companion for men and
      a boyfriend for women. The barriers related to the use of contraceptives were the
      financial stability of the partner, responsibility of the female partner when
      using contraceptives, limited capacity to negotiate choices, fear of abandonment
      by the male partner for demanding the use of contraceptives, and the reduction of
      sexual sensitivity with the use of condoms. CONCLUSIONS.: The barriers identified
      in this study limit the use of contraceptives and indicate the need to develop
      specific strategies to strengthen the interpersonal skills of adolescents and
      provide accurate information about the risks of unprotected sex.

PMID- 29364417
TI  - [Factors associated with slow walking speed in older adults of a district in
      Lima, Peru].
AB  - OBJECTIVES.: To determine the factors associated with slow walking speed in older
      adults living in a district of Lima, Peru. MATERIALS AND METHODS.: Analysis of
      secondary data. Adults older than 60 years were included in the study, while
      adults with physical conditions who did not allow the evaluation of the walking
      speed were excluded. The dependent variable was slow walking speed (less than 1
      m/s), and the independent variables were sociodemographic, clinical, and
      geriatric data. Raw and adjusted prevalence ratios (PR) were calculated with 95%
      confidence intervals (95% CI). RESULTS.: The study sample included 416 older
      adults aged 60 to 99 years, and 41% of the participants met the slow walking
      speed criterion. The factors associated with slow walking speed in this sample
      were female gender (PR, 1.45; 95% CI, 1.13-1.88), age > 70 years (PR, 1.73; 95%
      CI, 1.30- 2.30), lower level of education (PR, 2.07, 95% CI, 1.20-3.55), social
      familial problems (PR, 1.66; 95% CI, 1.08-2.54), diabetes mellitus (PR, 1.35; 95%
      CI, 1.01-1.80), and depression (PR, 1.41; 95% CI, 1.02-1.95). CONCLUSIONS.: The
      modifiable factors associated with slow walking speed in older adults included
      clinical and social-familial problems, and these factors are susceptible to
      interventions from the early stages of life.

PMID- 29364418
TI  - [Antibiotic resistance and distribution of serotypes of invasive pneumococcal
      strains isolated from hospitalized adults in Lima, Peru].
AB  - OBJECTIVES. : To describe the clinical characteristics, antibiotic resistance,
      and distribution of serotypes of bacterial strains that cause invasive
      pneumococcal disease (IPD) in adults. MATERIALS AND METHODS. : Case series.
      Pneumococcal strains were isolated from 2009 to 2011 from hospitalized adult
      patients with IPD in five hospitals and two laboratories located in Lima.
      RESULTS.: The analysis of data from 43 patients with IPD indicated that 58.2%
      were older than 60 years. The most common complications were pneumonia (39.5%),
      meningitis (30.2%), bacteremia (13.9%), peritonitis (11.6%), and septic arthritis
      (4.8%). The mortality rate was 28.9%, and 72.7% of cases involved patients older
      than 60 years. The pneumococcal strains were resistant to the following
      antibiotics: penicillin, 0% and 30.8% in non-meningitis and meningitis strains,
      respectively; ceftriaxone, 4.5% and 16.7% in non-meningitis and meningitis
      strains, respectively; trimethoprim/sulfamethoxazole, 69.0%; and erythromycin,
      35.7%. The most common serotypes were 19F, 23F, 6B, 14, and 6C. The percentage of
      vaccine strains was 44.2% for the 7-valent conjugate pneumococcal vaccine (PCV7)
      and PCV10, 51.2% for PCV13, and 60.4% for the 23-valent polysaccharide vaccine
      (PPV23). CONCLUSIONS.: Pneumococcus is an important pathogen in adults,
      particularly in older adults, owing to its high mortality rate.

PMID- 29364419
TI  - [Prevalence of latent tuberculosis infection in health workers from primary
      health care centers in Lima, Peru].
AB  - To evaluate the risk of tuberculosis (TB) infection, the General Directorate of
      Epidemiology of the Ministry of Health developed a sentinel surveillance system
      in health centers located in the Constitutional Province of Callao. This
      surveillance system included the diagnosis of latent tuberculosis infection (LTI)
      using interferon gamma release assays. The objective of the present study was to
      estimate the prevalence of LTI in health workers in a region with a high burden
      of TB. The prevalence of LTI in health workers was 56%. The prevalence of LTI was
      63% in workers with more than 10 years of service and 58-60% in workers with more
      than 35 years of service. The prevalence of LTI in health workers from primary
      health care centers was high, and longer service time was one of the main risk
      factors.

PMID- 29364421
TI  - [Association between aerobic capacity and quality of life in older adults in
      Colombia].
AB  - The objective of this study was to determine the association of aerobic capacity
      with health-related quality of life in 121 subjects using the modified Bruce
      protocol as a predictor of maximum oxygen consumption (VO2 maximum) and the SF-36
      quality of life questionnaire. The average maximum VO2 was 26.56 +/- 12.67
      mL/kg/min for men and 25.36 +/- 10.72 mL/kg/min for women. There was a
      significant association between sex and maximum VO2 (p = 0.018). Physical
      function and social function were the variables with the highest average values
      in the total sample, and aerobic capacity explained 15.3% of the physical
      function. In conclusion, low maximum VO2 was found in both sexes, and there was a
      significant association of maximum VO2 with physical function, physical
      performance, general health, vitality, and social function.

PMID- 29364420
TI  - [Multiresistance and factors associated with the presence of extended-spectrum
      beta-lactamases in Escherichia coli strains isolated from urine culture].
AB  - The empirical treatment of urinary infections is complicated by the presence of
      multiresistance and resistance to extendedspectrum beta-lactamases (ESBLs). The
      objective of this study was to describe the patterns of antibiotic resistance of
      Escherichia coli strains isolated from urine cultures and the clinical
      epidemiological factors associated with the presence of ESBLs in a pediatric and
      an adult group. A total of 353 strains were collected from the Emergency and
      Hospitalization Sector of the Cayetano Heredia Hospital over 14 months, and 45.9%
      of the isolated strains were multiresistant. The rate of resistance to ESBLs in
      the pediatric and adult population was 16.3% and 31.1%, respectively, and 63.6%
      of the resistant strains were isolated from outpatients. The presence of ESBLs
      was associated with hospitalization in pediatrics, use of diapers, and the
      presence of neurogenic bladder in adults. These factors should be considered in
      selection of an antibiotic treatment. Moreover, epidemiological reporting
      programs and models should be implemented for reduction of risk factors.

PMID- 29364422
TI  - [Interventions to prevent the development of overweight and obesity in children
      younger than five years].
AB  - Childhood obesity is one of the most severe public health problems worldwide. The
      present study describes the interventions used to prevent overweight and obesity
      in children younger than 5 years. The objective of the interventions was to
      stimulate breastfeeding, monitor the child's growth, and promote adequate
      complementary feeding by means of nutritional counseling using a responsive
      feeding approach in different settings, including health centers and residences.
      The interventions included physical activity and nutritional counseling, with the
      active participation of the parents. The quality of evidence from most studies
      was high because the evidence was derived from controlled clinical trials,
      systematic reviews, and meta-analyses. All interventions were conducted or could
      be replicated in Peru by adequate contextualization.

PMID- 29364423
TI  - [Diagnosis of anemia in populations at high altitudes].
AB  - Iron deficiency and overload are risk factors for numerous poor health outcomes,
      and thus the maintenance of iron homeostasis is vital. Considering that
      hemoglobin contains 70% of the total iron in the body, the World Health
      Organization (WHO) recommends the measurement of iron levels to calculate the
      rate of iron deficiency anemia (IDA), although WHO recognizes that IDA is not the
      only cause of anemia. As hemoglobin increases with altitude, WHO recommends
      correcting the cut-off point to define anemia at high altitudes. An objection to
      this correction is that the increase in hemoglobin at high altitudes is not
      universal and is not linear. In addition, individuals in older age groups have
      lower hemoglobin levels than those in younger age groups. In infants, children,
      pregnant women, and adults, the prevalence of anemia using corrected hemoglobin
      is 3-5 times higher than that using markers of iron status. State programs seek
      to control anemia by means of iron supplementation. However, these programs are
      ineffective, particularly for high-altitude populations. Therefore, the
      occurrence of iron deficiency at high altitudes is controversial. The serum
      levels of the hormone hepcidin, which regulates iron availability, are similar in
      individuals at high altitudes to those of individuals at sea level, indicating
      that iron deficiency does not occur at high altitudes. An additional problem when
      correcting hemoglobin at high altitudes is that the frequency of erythrocytosis
      is decreased. In conclusion, the correction of the cut-off point of hemoglobin at
      high altitudes to determine iron deficiency is inadequate.

PMID- 29364424
TI  - [Effect of anemia on child development: long-term consequences].
AB  - Anemia in children younger than 3 years is a public health problem in Peru and
      worldwide. It is believed that one of the primary causes of anemia is iron
      deficiency. Numerous studies and reviews have reported that iron deficiency
      limited psychomotor development in children and that, despite the correction of
      anemia, children with iron deficiency experienced poorer long-term performance in
      cognitive, social, and emotional functioning. These outcomes were reported in
      observational studies, follow-up studies, and experimental studies with a control
      group. Anemia can decrease school performance, productivity in adult life,
      quality of life, and the general income of affected individuals. Here we describe
      possible mechanisms underlying the effect of iron deficiency, with or without
      anemia, on childhood development. The high rate of anemia in this age group is a
      cause for concern. Moreover, anemia should be prevented in the first year of life
      to avoid long-term negative effects on individual development.

PMID- 29364425
TI  - [Evaluation of electronic health programs in Peru: multidisciplinary approach and
      current perspectives].
AB  - Electronic health (eHealth) requires a multidisciplinary approach and involves
      different areas of knowledge, including medicine, computer science, engineering,
      sociology, anthropology, social work, administration, law, and communication
      sciences. The assessment of eHealth should consider that information and
      communication technologies (ICTs) are only part of the information system of an
      organization. Understanding the human factors involved in health systems, the
      environment, and the contexts in which ICTs are used in health is essential. The
      objectives of this study were to describe the status of the assessment of eHealth
      in Peru and to discuss the strategies for multidisciplinary evaluation that
      should be considered to achieve the success and sustainability of these
      initiatives based on national and international experience.

PMID- 29364426
TI  - [Nevoid basal-cell carcinoma syndrome (Gorlin Syndrome): report of two cases and
      review of the literature].
AB  - Gorlin syndrome (GS) is a genetic disorder with an autosomal dominant inheritance
      pattern, with complete penetrance and variable expressivity. GS is caused by
      germline mutations in the genes PTCH1 or SUFU, which are components of the Sonic
      hedgehog molecular pathway. GS is characterized by the presence of multiple
      nevoid basal cell carcinomas, odontogenic cysts, calcification of the brain
      sickle, and lesions in the palms and soles. This study is the first to report
      cases in Peru of patients with GS who underwent genetic evaluation and
      counseling. We present two GS cases that meet the clinical criteria for the
      syndrome and review the literature.

PMID- 29364427
TI  - [On the need for a taxonomic update].

PMID- 29364428
TI  - [Malabsorption of lactose in adolescent members of a football club].

PMID- 29364429
TI  - New perspectives for the treatment of Hansen's disease.

PMID- 29364430
TI  - Leprosy: current situation, clinical and laboratory aspects, treatment history
      and perspective of the uniform multidrug therapy for all patients.
AB  - In this review, the most relevant and current epidemiological data, the main
      clinical, laboratory and therapeutical aspects of leprosy are presented. Detailed
      discussion of the main drugs used for leprosy treatment, their most relevant
      adverse effects, evolution of the therapeutic regimen, from dapsone as a
      monotherapy to the proposed polychemotherapy by World Health Organization (WHO)
      can be found in this CME. We specifically highlight the drug acceptability,
      reduction in treatment duration and the most recent proposal of a single
      therapeutic regimen, with a fixed six months duration, for all clinical
      presentations, regardless of their classification.

PMID- 29364431
TI  - Risk factors associated with actinic prurigo: a case control study.
AB  - BACKGROUND: Actinic prurigo (AP) is an idiopathic photodermatosis. Although its
      initial manifestations can appear in 6 to 8-year-old children, cases are
      diagnosed later, between the second and fourth decades of life, when the injuries
      are exacerbated. OBJECTIVE: To identify risk factors associated with clinical
      manifestations of AP such as skin and mucosal lesions. METHODS: Thirty patients
      with AP and 60 controls were included in the study, the dependent variable was
      the presence of skin or labial mucosal lesions, the independent variables were
      age, sex, solar exposure, living with pets or farm animals, exposure to wood
      smoke, smoking habit, years smoking, and hours spent per day and per week in
      contact with people who smoke. RESULTS: Of the 30 diagnosed AP patients, 66.7%
      were female. Patients age ranged from 7 to 71 years and the mean age was 35.77 +/
      14.55 years. We found significant differences with the age and cohabitation with
      farm animals. Those who lived with farm animals presented 14.31 times higher
      probability of developing AP (95% CI 3-78.06). STUDY LIMITATIONS: This is a case
      control study; therefore, a causal relationship cannot be proven, and these
      results cannot be generalized to every population. CONCLUSIONS: The
      identification of factors related to the development of AP increases our
      knowledge of its physiopathology. Moreover, identifying antigens that possibly
      trigger the allergic reaction will have preventive and therapeutic applications
      in populations at risk of AP.

PMID- 29364432
TI  - Effectiveness of syndromic management for male patients with urethral discharge
      symptoms in Amazonas, Brazil.
AB  - BACKGROUND: Urethral discharge syndrome (UDS) is characterized by the presence of
      purulent or mucopurulent urethral discharge.The main etiological agents of this
      syndrome are Neisseria gonorrhoeae and Chlamydia trachomatis. OBJECTIVES: To
      evaluate the effectiveness of the syndromic management to resolve symptoms in
      male urethral discharge syndrome cases in Manaus, Amazonas, Brazil. METHODS:
      Retrospective cohort of male cases of urethral discharge syndrome observed at a
      clinic for sexually transmitted disease (STD) in 2013. Epidemiological and
      clinical data, as well as the results of urethral swabs, bacterioscopy, hybrid
      capture for C.trachomatis, wet-mount examination, and culture for N.gonorrhoeae,
      were obtained through medical chart reviews. RESULTS: Of the 800 urethral
      discharge syndrome cases observed at the STD clinic, 785 (98.1%) presented only
      urethral discharge syndrome, 633 (79.1%) returned for follow-up, 579 (91.5%) were
      considered clinically cured on the first visit, 41(6.5 %) were considered cured
      on the second visit, and 13(2.0%) did not reach clinical cure after two
      appointments. Regarding the etiological diagnosis, 42.7% of the patients
      presented a microbiological diagnosis of N.gonorrhoeae, 39.3% of non-gonococcal
      and non-chlamydia urethritis, 10.7% of C.trachomatis and 7.3% of co-infection
      with chlamydia and gonococcus. The odds of being considered cured in the first
      visit were greater in those who were unmarried, with greater schooling, and with
      an etiological diagnosis of gonorrhea. The diagnosis of non-gonococcal urethritis
      reduced the chance of cure in the first visit. STUDY LIMITATION: A study
      conducted at a single center of STD treatment. CONCLUSION: Syndromic management
      of male urethral discharge syndrome performed in accordance with the Brazilian
      Ministry of Health STD guidelines was effective in resolving symptoms in the
      studied population. More studies with microbiological outcomes are needed to
      ensure the maintenance of the syndromic management.

PMID- 29364433
TI  - Prevalence and factors associated with exposure to sunlight and sunscreen among
      physical education teachers in Pelotas, southern Brazil.
AB  - BACKGROUND: Decreasing the time of exposure to the sun and increasing sunscreen
      use are important actions to prevent skin cancer. OBJECTIVE: This study aimed to
      verify the prevalence of exposure to the sun and the use of sunscreen, as well as
      associated factors among physical education teachers of the basic education
      network from city of Pelotas, southern Brazil. METHODS: A census type study was
      conducted with physical education teachers of the basic education network from
      Pelotas. This study assessed the time of exposure to the sun in the workplace for
      at least 20 min, between 10am and 4pm, and the use of sunscreen during the
      workday. RESULTS: 188 teachers answered the questionnaire. The prevalence of
      exposure to the sun between 10:00am and 4:00pm was 89.2% (95% CI of 83.8% 
      93.3%), while sunscreen use was 63.3% (95% CI of 56.0% -70.2%). However, when the
      sample was stratified by sex, women reported a higher rate of sunscreen use
      (78.5% -95% CI of 72.2-84.3) than men (38.9% -95% CI of 31.8-46.2) (p<0.001).
      Teachers with longer work weeks were at greater risk of exposure to the sun. In
      addition, women, with normal weight and who worked less hours, were more likely
      to use sunscreen. STUDY LIMITATIONS: Cross-sectional study and lack of
      information on the proper use and frequency of use of sunscreen. CONCLUSION:
      Physical education teachers were highly exposed to solar radiation, and less than
      two-thirds used sunscreen during the workday. Interventions with this
      professional group are necessary to reduce the risk of skin cancer.

PMID- 29364434
TI  - Global and gene-specific DNA methylation and hydroxymethylation in human skin
      exposed and not exposed to sun radiation.
AB  - BACKGROUND: epigenomes can be influenced by environmental factors leading to the
      development of diseases. OBJECTIVE: To investigate the influence of sun exposure
      on global DNA methylation and hydroxymethylation status and at specific sites of
      the miR-9-1, miR-9-3 and MTHFR genes in skin samples of subjects with no history
      of skin diseases. METHODS: Skin samples were obtained by punch on sun-exposed and
      sun-protected arm areas from 24 corpses of 16-89 years of age. Genomic DNA was
      extracted from skin samples that were ranked according to Fitzpatrick's criteria
      as light, moderate, and dark brown. Global DNA methylation and hydroxymethylation
      and DNA methylation analyses at specific sites were performed using ELISA and
      MSP, respectively. RESULTS: No significant differences in global DNA methylation
      and hydroxymethylation levels were found among the skin areas, skin types, or
      age. However, gender-related differences were detected, where women showed higher
      methylation levels. Global DNA methylation levels were higher than
      hydroxymethylation levels, and the levels of these DNA modifications correlated
      in skin tissue. For specific sites, no differences among the areas were detected.
      Additional analyses showed no differences in the methylation status when age,
      gender, and skin type were considered; however, the methylation status of the miR
      9-1 gene seems to be gender related. STUDY LIMITATIONS: there was no separation
      of dermis and epidermis and low sample size. CONCLUSION: sun exposure does not
      induce changes in the DNA methylation and hydroxymethylation status or in miR-9
      1, miR-9-3 and MTHFR genes for the studied skin types.

PMID- 29364435
TI  - Narrowband UV-B phototherapy in childhood atopic dermatitis: efficacy and safety.
AB  - BACKGROUND: Narrow-band UVB is the most innovative steroid sparing treatment in
      atopic dermatitis. There are studies showing efficacy of Narrow-band UVB in
      childhood atopic dermatitis, but there is lack of clinical trials in the
      literature determining the length of remission. Therefore, we sought to highlight
      its efficacy, safety and its post-treatment efficacy in childhood atopic
      dermatitis. OBJECTIVE: To assess the clinical efficacy, safety of Narrow-band UVB
      in the treatment of paediatric atopic dermatitis and length of remission during 2
      years of post-treatment follow-up. METHODS: Thirty children (4-14 years) having
      moderate to severe AD (SCORAD index > 25) were enrolled for 12 weeks. Narrow-band
      UVB phototherapy was administered twice a week on non-consecutive days for three
      months. SCORAD index was calculated by the same dermatologist at baseline, 6th,
      12th, 18th and 24th treatment session. Secondary outcomes were measured using
      visual analog scale for pruritus and sleep loss. Patients were also followed-up
      for 2 years to know the length of remission after end of therapy. RESULTS: There
      was a significant reduction in SCORAD index at 6th, 12th, 18th and 24th treatment
      session in comparison to baseline. This improvement in SCORAD was also maintained
      during the 2 years of post-treatment follow-up period. Consequently, pruritus and
      sleep loss improved significantly from baseline to end of therapy and even during
      the 1st and 2nd year of follow-up. STUDY LIMITATION: Open-label trial without
      control group. CONCLUSIONS: Narrow-band UVB is an efficacious and safe modality
      of treatment in childhood atopic dermatitis with good therapeutic index and
      minimal side effects.

PMID- 29364436
TI  - Investigation of Demodex folliculorum frequency in patients with polycystic ovary
      syndrome.
AB  - BACKGROUND: Background: Demodex mites are acari that reside in the pilosebaceous
      unit of the skin and have been associated with skin disorders. OBJECTIVE: The
      objective of this study was to investigate the prevalence of Demodex folliculorum
      (D. folliculorum) mites in polycystic ovary syndrome patients as well as to
      examine the relationship between Demodex infestation and the presence of acne and
      oily or dry skin types in polycystic ovary syndrome patients. METHODS: 41
      polycystic ovary syndrome patients and 47 non-polycystic ovary syndrome control
      subjects were enrolled in the study. polycystic ovary syndrome was diagnosed
      according to the revised 2003 ESHRE/ASRM polycystic ovary syndrome Consensus
      Workshop Group diagnostic criteria. Microscopic examination of D. folliculorum
      mites was carried out by standardized skin surface biopsy. The result was
      considered positive when there were more than 5 mites per cm2. RESULTS: D.
      folliculorum was positive in 53.7% of the polycystic ovary syndrome patients and
      31.9% of the non-polycystic ovary syndrome group (p=0.052). Demodex positivity
      was significantly associated with acne (p=0.003) and oily skin (p=0.005) in the
      polycystic ovary syndrome patients but not in the controls. STUDY LIMITATION: Our
      study is limited by the relatively small number of subjects and the observational
      nature of the study design. CONCLUSION: Demodex mites might have a role in acne
      pathogenesis in patients with polycystic ovary syndrome. Anti-Demodex treatment
      may increase the response to treatment of acne. Further studies are indicated.

PMID- 29364437
TI  - Prepubertal and postpubertal vitiligo: a multivariate comparative study in 375
      patients.
AB  - BACKGROUND: The onset of vitiligo during childhood is common. Limited data exist
      that compare the clinical associations of prepubertal and postpubertal vitiligo
      in Arabs. OBJECTIVE: To compare the clinical profile of pre and postpubertal
      onset vitiligo. METHODS: A cross-sectional observational study was conducted. The
      Vitiligo European Task Force questionnaire was completed for each patient.
      RESULTS: A total of 375 patients were included; 199 had postpubertal vitiligo
      (>12 years), and 176 had prepubertal onset vitiligo (<12years). There were more
      females in the prepubertal group (49%) than in the postpubertal group (29%), p
      value <0.001. The prepubertal group has had more involvement than the
      postpubertal group (45% vs 30%, p=0.004). Only 8 cases of segmental vitiligo were
      observed; five were observed in the prepubertal group of patients. Female gender
      (OR=2.3; 95% CI:1.5, 3.5), presence of halo nevus (OR=2.2; 95% CI:1.1, 4.4) and
      face involvement (OR=1.9; 95% CI:1.2, 2.9) were positively associated with
      prepubertal vitiligo. Stress, as an onset factor, was positively associated
      (OR=0.51; 95% CI:0.3, 0.8) with postpubertal onset vitiligo. STUDY LIMITATIONS: A
      possible selection bias toward more severe vitiligo cases can be a limitation,
      because the study was conducted in a clinic specialized in vitiligo. Moreover, a
      likelihood of false recall bias cannot be excluded. CONCLUSIONS: Our data present
      clinical evidence that vitiligo behaves mostly the same way in the prepubertal
      group as in the postpubertal group. However, female over-representation, more
      face involvement and more halo nevi were observed in prepubertal vitiligo, while
      stress was more prevalent as an aggravating factor in postpubertal vitiligo
      patients.

PMID- 29364438
TI  - Prevalence and heritability of psoriasis and benign migratory glossitis in one
      Brazilian population.
AB  - BACKGROUND: An oral condition associated to psoriasis is benign migratory
      glossitis. The review of the literature does not show any publication about
      heritability in both soriasis and benign migratory glossitis and prevalence of
      psoriasis in the Brazilian population. OBJECTIVE: This research was carried out
      in order to determine the prevalence of psoriasis and benign migratory glossitis
      in the Brazilian population from a Brazilian sample, as well as the heritability
      in these conditions. METHODS: Six thousand patients were studied from the records
      of the outpatient dermatology department. The sample had 129 patients with
      cutaneous psoriasis, 399 with benign migratory glossitis without psoriasis and a
      control group with 5,472 patients. After data collection, the statistical
      analysis was made using Woolf, Chi-square and Falconer tests. RESULTS: The
      prevalence of psoriasis was 2.15% and the benign migratory glossitis was 7.0%.
      The prevalence of benign migratory glossitis in the psoriasis group was high
      (16.3%), and that was statistically significant. Family history in the psoriasis
      group was 38% for the condition itself and 2,75% for benign migratory glossitis
      and in the benign migratory glossitis group was 17.54% for the condition itself
      and 1.5% for psoriasis. The study of heritability was 38.8% for psoriasis and
      36.6% for benign migratory glossitis, both with medium heritability. STUDY
      LIMITATIONS: This study was only in the state of Sao Paulo. CONCLUSION: This is
      the first publication that quantifies how much of these conditions have a genetic
      background and how important the environmental factors are in triggering them.

PMID- 29364439
TI  - Thickness of carotid intima and epicardial fat in rosacea: a cross-sectional
      study.
AB  - BACKGROUND: Rosacea is a chronic facial skin disease associated with excessive
      inflammatory response to various triggers. Although some studies have supported
      the increased risk of cardiovascular diseases in rosacea, it has not been
      completely accepted. OBJECTIVE: We aimed to investigate epicardial fat thickness
      and carotid intima-media thickness as cardiovascular risk predictors in rosacea
      patients. METHODS: We conducted a cross-sectional study including 40 rosacea
      patients and 40 controls. Demographic data, epicardial fat thickness, carotid
      intima-media thickness, lipid parameters, biochemical parameters, presence of
      insulin resistance, and presence of metabolic syndrome of the participants were
      recorded. RESULTS: Forty rosacea patients (31 female and 9 male) and 40 controls
      (30 female and 10 male) were enrolled in the study. Rosacea patients had
      significantly higher epicardial fat thickness and carotid intima-media thickness
      volumes than controls (P<0.001). In the multivariate logistic regression
      analysis, epicardial fat thickness was independently related to presence of
      rosacea (P<0.001, OR=13.31). In the multiple linear regression analysis, the
      epicardial fat thickness was independently associated with rosacea (beta= 0.47,
      P<0.001), carotid intima-media thickness (beta= 0.36, P<0.001), and systolic
      blood pressure (beta=0.19, P=0.015) and the carotid intima-media thickness was
      independently associated with epicardial fat thickness (beta= 0.6, P<0.001). The
      epicardial fat thickness levels were correlated with carotid intima-media
      thickness (r=0.63, P<0.001), LDL (r=0.23, P=0.037), systolic blood pressure
      (r=0.45, P<0.001), and diastolic blood pressure levels (r=0.37, P=0.001). The
      carotid intima-media thickness levels were correlated with epicardial fat
      thickness (r=0.63, P<0.001), systolic blood pressure (r=0.04, P<0.001), and
      diastolic blood pressure levels (r=0.27, P=0.016). STUDY LIMITATIONS: The small
      number of participants. CONCLUSIONS: Examination and follow-up of rosacea
      patients for cardiovascular diseases may be recommended practices.

PMID- 29364440
TI  - How relevant are vascular endothelial growth factor and intercellular adhesion
      molecule in the systemic capillary leak syndrome of psoriasis?
AB  - Psoriasis is a chronic disease, characterized by erythematous scaly lesions,
      presented in eight different forms: plaques, guttate, pustular, erythrodermic,
      inverse, nail and scalp psoriasis, and psoriatic arthritis. Its development
      depends on genetic factors, external stimulus and immune response alteration.1
      Proinflammatory cytokines such as TNF-alpha, IL-12 and 23 may also be involved.
      In the worst cases, systemic complications linked to endothelial alterations may
      occur. A literature review was conducted for a better understanding of what roles
      VEGF (vascular endothelial growth factor) and ICAM-1 (intercellular adhesion
      molecule) have, among other cytokines, in systemic capillary leak syndrome,
      involved in erythrodermic and pustular psoriasis, the most unstable forms of the
      disease.

PMID- 29364441
TI  - Cancer immunology and melanoma immunotherapy.
AB  - The stimulation of the immune system, in order to generate an attack against
      cancer cells, similarly to that which occurs in infectious disease, has long been
      matter of interest in oncology; however, only limited success has been achieved,
      with different treatment strategies tested in recent years. The development of
      new immune checkpoint inhibitors is currently changing this scenario, and
      immunotherapy is becoming a real choice among traditional cytotoxic treatments to
      fight cancer. Recent reports have shown efficacy and safety with the use of
      pembrolizumab, nivolumab, and ipilimumab for the treatment of different
      neoplasms, especially melanoma. In this article, we propose a review of the
      mechanisms of action involved in cancer immunology, the response evaluation of
      immunotherapies, and its toxicity profile, as well as a summary of the main
      clinical trials that led to the adoption of these new drugs for melanoma
      treatment.

PMID- 29364442
TI  - Rare desmoplastic trichilemmoma associated with sebaceous nevus.
AB  - Nevus sebaceous of Jadassohn is a congenital hamartoma that usually affects the
      scalp and face. Several benign or malignant neoplasias may develop in the lesion
      and the most common are trichoblastoma, syringocystadenoma papilliferum, and
      basal cell carcinoma. Trichilemmoma is a benign solid tumor originating from
      external sheath cells of pilosebaceous follicles. When it is characterized by a
      central zone of desmoplasia, it is called desmoplastic trichilemmoma. We report a
      case of a 58-year-old patient who developed a tumor in a sebaceous nevus. We
      performed a total excision of the lesion. Histopathological diagnosis was
      compatible with desmoplastic trichilemmoma. Our literature review reveals that
      the occurrence of trichilemmoma desmoplastic is unusual. Moreover, it can mimic
      an invasive carcinoma on histological and clinical examinations. This fact
      confirms the importance of reporting the occurrence of this rare cancer in a
      nevus sebaceous of Jadassohn.

PMID- 29364443
TI  - Milker's nodules: classic histological findings.
AB  - Milker's nodule is an occupational dermatovirose caused by Parapoxvirus, which is
      self-limited and, due to the lack of information of health professionals, may
      lead to underdiagnosis. We present two cases with exuberant manifestations and
      classic histopathologic findings. Case 1: Male, 19 years of age, milker,
      presented nodules and blisters on his palm for 15 days. Case 2: Male, 33 years of
      age, administrative assistant, presented erythematous nodules on his palms with
      lymphangitis for 5 days. He had milked a cow one week before the onset of the
      lesions. In both cases, the histopathology was representative and coincident with
      the clinical hypothesis. The lesions have presented complete involution. Milker's
      nodule diagnosis is based on clinical presentation, epidemiology, and
      histopathology. The knowledge of this disease is essential for its correct
      diagnosis, as well as to guide the implementation of public health measures and
      the appropriate treatment of sick cattle.

PMID- 29364444
TI  - Describing numerical variables: which are the most appropriate parameters to
      describe the data?
AB  - The proper description of numerical variables is very important when presenting a
      set of data. Measures of central tendency and dispersion are used to adequately
      understand a set of numerical variables. Knowledge of the properties of these
      measures and their adequate use provide the reader with a better understanding of
      the results of a study.

PMID- 29364445
TI  - Dermatoscopic signs in cutaneous leishmaniasis.
AB  - Dermoscopy is a non-invasive technique widely used to aid in the characterization
      and diagnosis of pigmented skin lesions. Recently, it has also been employed for
      the evaluation of non-pigmented skin tumours, and inflammatory and infectious
      cutaneous diseases. Although the diagnosis of cutaneous leishmaniasis is
      confirmed by the demonstration of amastigotes in infected skin or by the growth
      of promastigotes in culture medium, dermoscopy could be useful as a further
      diagnostic test. We report a patient with a nodular lesion located on the right
      cheek for almost two years. The lesion was clinically suggestive of cutaneous
      leishmaniasis. Dermoscopy showed yellow tears, erythema and vascular structures.
      The diagnosis was confirmed by the demonstration of amastigotes in a skin
      scraping sample.

PMID- 29364446
TI  - Morbihan disease: a therapeutic challenge.
AB  - Morbihan disease is a rare condition characterized by chronic and persistent
      erythematous solid edema localized on the face. It is believed to be a
      complication of rosacea and may occur at any stage of the disease. Features of
      this condition include variable therapeutic response and great refractoriness. We
      report a case of a 61-year-old man with rosacea history diagnosed with Morbihan
      disease, who showed excellent therapeutic response with the combination of
      deflazacort and oral isotretinoin but developed recurrence after corticosteroid
      discontinuation. We believe that in severe cases of lymphedema of the face this
      combination is effective and corticosteroid suspension should be done slowly and
      gradually.

PMID- 29364447
TI  - Lupus miliaris disseminatus faciei.
AB  - Lupus miliaris disseminatus faciei is a rare inflammatory dermatosis of unknown
      etiology that primarily affects young adults. Clinically, it is characterized by
      an asymptomatic papular eruption mainly involving the central face, typically on
      and around the eyelids. Characteristic histopathological features include dermal
      epithelioid cell granulomas with central necrosis and surrounding lymphocytic
      infiltrate with multinucleate giant cells. Lupus miliaris disseminatus faciei has
      a spontaneously resolving course, yet can be cosmetically debilitating given the
      location and potential for scarring. Treatment is difficult and there is a lack
      of controlled studies. We report a new case of lupus miliaris disseminatus faciei
      successfully treated with minocycline and systemic steroids, and briefly discuss
      its nosology and therapeutic options.

PMID- 29364448
TI  - Infantile myofibromatosis.
AB  - Infantile myofibromatosis is a mesenchymal disorder characterized by the fibrous
      proliferation of the skin, bone, muscle and viscera. It is the most common
      fibrous tumor in childhood. We present a newborn with skin and bone disease
      without visceral involvement, who showed good response to vinblastine and
      methotrexate. Clinical features, etiology, diagnosis, and treatment are reviewed.

PMID- 29364449
TI  - Sweet syndrome-like cutaneous drug reaction.
AB  - Cutaneous drug reactions are adverse reactions to medications that may present
      with different clinical features, ranging from localized to generalized lesions.
      In this report we describe a case of an unusual drug reaction, resembling the
      morphology of Sweet syndrome lesions. The patient had a psychiatric illness and
      was using thioridazine hydrochloride for one year. He developed infiltrated and
      grouped erythematous lesions on the elbows and knees three days after commencing
      multiple drugs (promethazine, haloperidol, mirtazapine and levomepromazine).
      After suspension of these four drugs and after the use of glucocorticoids, the
      patient had significant clinical improvement.

PMID- 29364450
TI  - Rapidly involuting congenital hemangioma.
AB  - Rapidly involuting congenital hemangioma is a rare vascular tumor that generally
      has a good prognosis. The authors describe a case of a newborn girl with a left
      cervical vascular lesion. Image exams were performed, and the lesion slowly
      decreased, leaving redundant skin. Considering all of the findings, a final
      diagnosis of a rapidly involuting congenital hemangiomas was suspected.

PMID- 29364451
TI  - Primary treatment of early fistula of parotid duct with botulinum toxin type A
      injection.
AB  - Salivary duct injury can be idiopathic, iatrogenic, or post-trauma and may result
      in sialocele or fistula. Most injuries regress spontaneously and botulinum toxin
      A is one of several therapeutic possibilities. We report a case of iatrogenic
      injury to the parotid duct after Mohs' micographic surgery for a squamous cell
      carcinoma excision in the left jaw region, treated by injection of botulinum
      toxin type A. Although the fistula by duct injury can be self-limiting, botulinum
      toxin injection by promoting the inactivity of the salivary gland allows rapid
      healing of the fistula.

PMID- 29364452
TI  - Piccardi-Lassueur-Graham-Little syndrome associated with frontal fibrosing
      alopecia.
AB  - Piccardi-Lassueur-Graham-Little syndrome is a rare entity characterized by
      progressive scarring alopecia of the scalp and keratotic papules on hairless
      skin, associated with non-scarring alopecia in the axilla and pubic area or
      lichen planus lesions. We describe the case of a 70-year-old woman who presented
      a Piccardi-Lasseur-Graham-Little syndrome, along with frontal fibrosing alopecia.

PMID- 29364453
TI  - Moyamoya syndrome associated with neurofibromatosis type 1 in a pediatric
      patient.
AB  - Neurofibromatosis type 1 is a multisystem genetic disease of autosomal dominant
      transmission that reveals important cutaneous manifestations such as cafe-au-lait
      spots, multiple neurofibromas, and ephelides in skin fold areas, as well as
      hamartomatous lesions in the eyes, bones, glands, and central nervous system.
      Moyamoya disease is a rare progressive vaso-occlusive disorder that occurs with
      important ischemic cerebrovascular events. Despite the rarity of this association
      in childhood, children diagnosed with neurofibromatosis type 1 and focal
      neurologic symptoms should be investigated for moyamoya syndrome. The present
      study reports the case of a pediatric patient with a rapidly progressive
      cerebrovascular accident and a late diagnosis of Neurofibromatosis type 1
      associated with moyamoya disease.

PMID- 29364454
TI  - Circular hairs: nomenclature and meanings.
AB  - Trichoscopy has become an essential tool for the diagnosis of various diseases
      that affect the hair and scalp. Through dermatoscopy we identified a set of
      findings that share a circular shape of hair shafts. The objective of this study
      is to distinguish among the various forms of circular hairs in order to identify
      their peculiarities and to describe in which skin disorders they can be found.

PMID- 29364455
TI  - Case for diagnosis. Palate perforation due to cocaine use.
AB  - We report a 42-year-old cocaine addicted female patient referred for evaluation
      of hard palate ulceration resulting in oro-sinus communication with difficulties
      in swallowing and phonation, an rhino-sinusitis. Acrylic and removable silicone
      prosthesis was prescribed to relieve severe functional disorders. It is essential
      that the patient permanently abandons cocaine use to perform surgical
      reconstruction.

PMID- 29364456
TI  - Pellagra affecting a patient with Crohn's disease.
AB  - Pellagra is a nutritional disease caused by a deficiency of niacin. It may lead
      to death if not identified and treated timely. We review the literature and
      report a female patient presented with clinical features of pellagra as a
      complication of Crohn's disease.

PMID- 29364457
TI  - Epidemiological profile of elderly patients with non-melanoma skin cancer seen at
      the dermatology outpatient clinic of a public hospital.
AB  - Basal cell carcinoma and Squamous cell carcinoma, referred to as non-melanoma
      skin cancer, are the most common malignancies in humans. Their incidence is
      increasing worldwide every year. In Brazil, even with the advent of educational
      campaigns on photoprotection and laws that banned tanning beds, they are the most
      frequent neoplasias, representing a public health problem recognized by the
      Ministry of health.

PMID- 29364458
TI  - Nail psoriasis treated with pulsed dye laser.
AB  - Nail changes are present in about 50% of psoriasis patients and tend to be
      refractory to conventional treatments. Pulsed dye laser has emerged as an
      alternative therapy. Our aim is to evaluate the efficacy of pulsed dye laser in
      nail psoriasis and the impact of treatment on quality of life. Fourteen patients
      were treated in monthly sessions for three months. The outcome assesment was made
      by the Nail Psoriasis Severity Index (NAPSI). The median improvement in the
      scores of the overall NAPSI, nail bed NAPSI, and nail matrix NAPSI were 44.2% (P
      = 0.002), 50% (P = 0.033) and 65.1% (P = 0.024), respectively.

PMID- 29364459
TI  - Optimizing suction blister epidermal graft technique in the surgical treatment of
      vitiligo.
AB  - Surgical management of vitiligo is considered an excellent terapeutic option for
      recalcitrant cases, provided the disease is stable and there is absence of
      Koebner phenomenom. Among surgical modalities, Suction Blister Epidermal Graft is
      a low cost and effective option (65 to 100% repigmentation can be achieved in up
      to 80% of patients). We describe how it can be optimized by using an alternative
      suction equipment, by customization of graft format and by application of an
      anesthetic technique that substantially reduces procedure time.

PMID- 29364460
TI  - Use of botulinum toxin type A in Frey's syndrome.

PMID- 29364461
TI  - Pseudo "fringe sign" in frontal fibrosing alopecia.

PMID- 29364462
TI  - Dapsone-induced agranulocytosis in patients with Hansen's disease.

PMID- 29364463
TI  - Pseudoxanthoma elasticum-like papillary dermal elastolysis.

PMID- 29364465
TI  - Association between lipid profiles and osteoporosis in postmenopausal women: a
      meta-analysis.
AB  - OBJECTIVE: To investigate the relationship between blood lipid profiles and
      osteoporosis in postmenopausal women. MATERIALS AND METHODS: A comprehensive
      search of the literature related to lipid profiles and postmenopausal
      osteoporosis was conducted in Wanfang Database, CNKI, PubMed (1950-2015) and
      EMBASE (1974-2015). Appropriate studies were selected according to pre-defined
      exclusion criteria, and the levels of high-density lipoprotein cholesterol (HDL),
      low-density lipoprotein cholesterol (LDL), triglycerides (TG) and total
      cholesterol (TC) were compared between osteoporosis and normal density groups.
      Statistical analysis was performed using RevMan5.3. RESULTS: Ten published
      articles were selected for meta-analysis. The results showed that the levels of
      HDL, LDL, TC were higher in the osteoporosis group than the normal density group,
      whereas the levels of TG were lower in the osteoporosis group (HDL: MD = 2.63,
      95% CI: 0.43 to 4.84, p = 0.02; LDL: MD = 9.67, 95% CI: -0.10 to 19.44, p =
      0.0532; TG: MD = -0.42, 95% CI: -17.52 to 16.67, p = 0.96; TC: MD = 14.82, 95%
      CI: 2.84 to 26.80, p = 0.02). There was no statistical difference in LDL and TG.
      CONCLUSIONS: The serum levels of HDL and TC are higher in postmenopausal
      osteoporosis patients, and may thus be potentially useful indicators to reflect
      the process of osteoporosis in these women. More research is needed to determine
      the relationship between LDL, TG and postmenopausal osteoporosis.

PMID- 29364464
TI  - Reactivation of Chagas-Mazza disease during treatment with infliximab.

PMID- 29364466
TI  - Adipose-derived stem cells improve neovascularization in ischemic flaps in
      diabetic mellitus through HIF-1alpha/VEGF pathway.
AB  - OBJECTIVE: To investigate the improvement effect of adipose-derived stem cells on
      neovascularization in an ischemic flap in diabetes mellitus (DM), and to explore
      the mechanism of hypoxia-inducible factor 1alpha (HIF-1alpha)/vascular
      endothelial growth factor (VEGF) pathway. MATERIALS AND METHODS: A total of 60
      male Sprague-Dawley (SD) rats were divided into control group, model group, and
      adipose-derived stem cells (ADSCs) group. The survival rate of the flap and the
      number of new blood vessels were measured. The content of VEGF was determined by
      enzyme-linked immunosorbent assay (ELISA) kit. Then, the expressions of HIF
      1alpha and VEGF in each group were measured by immunohistochemistry. Reverse
      transcriptase polymerase chain reaction (RT-PCR) method and Western blotting
      assay were used to detect the mRNA and protein expression of HIF-1alpha and VEGF
      in each group. RESULTS: Compared with control group, the flap survival rate of
      model group was decreased significantly, and the number of new blood vessels was
      also decreased significantly. Compared with model group, the flap survival rate
      of ADSCs group was increased significantly, and the number of new blood vessels
      was also increased significantly. The results of ELISA showed that compared with
      control group, the level of VEGF in model group was lower than that in model
      group, and the level of VEGF in the ADSC group was significantly higher than that
      in the model group. IHC results showed that both HIF-1alpha and VEGF proteins
      were decreased significantly in model group, whereas the expression of HIF-1alpha
      and VEGF in the ADSCs group was increased significantly. The results of RT-PCR
      and the Western blotting showed the mRNA and protein expressions in model group
      were all decreased, while those in ADSCs group were significantly increased (p <
      0.05). CONCLUSIONS: ADSCs can improve the neovascularization of diabetic ischemic
      skin by regulating the HIF-1alpha/VEGF pathway.

PMID- 29364467
TI  - MiR-214-3p inhibits beta-catenin signaling pathway leading to delayed fracture
      healing.
AB  - OBJECTIVE: To investigate the effect of micro ribonucleic acid (miR)-214-3p on
      the fracture healing process of mice and its mechanism. MATERIALS AND METHODS: 90
      mice were selected and randomly divided into three groups to establish the right
      tibial fracture model. AgomiR-214-3p or agomiR negative control (agomiR-NC), or
      the same volume of phosphate-buffered saline (PBS), was injected locally at 0 d,
      7 d, 14 d and 21 d after operation, respectively. At the end of the experiment,
      the imageological observation, histological observation and the detection of
      callus osteocalcin level were conducted for mice in each group to evaluate the
      fracture healing. At the same time, Real-time polymerase chain reaction (RT-PCR)
      and Western blotting were used to detect the expression of beta-catenin at
      different time points in each group. RESULTS: Imageological and histological
      observations showed that the fracture lines of mice in the PBS injection group
      and the agomiR-NC injection group were found to be healed at 28 d after
      fractures, while fuzzy fracture lines could be seen in mice with fewer calluses
      in the agomiR-214-3p injection group, and the expression level of osteocalcin at
      each time point in the agomiR-214-3p injection group was decreased compared with
      that in the control group. In addition, RT-PCR and Western blotting results
      revealed that the expression level of the miR-214-3p target gene, beta-catenin,
      was decreased at each time point in the agomiR-214-3p group compared with that in
      the control group. CONCLUSIONS: MiR-214-3p delays the fracture healing by
      inhibiting the Wnt/beta-catenin signaling pathway.

PMID- 29364468
TI  - Correlations between CXCL13, IL-24 genes and wrist arthritis.
AB  - OBJECTIVE: To investigate the relationship between B lymphocyte chemokine 1
      (CXCL13) and interleukin-24 (IL-24) gene and wrist arthritis. PATIENTS AND
      METHODS: A total of 122 cases of patients with wrist arthritis treated in our
      hospital from May 2013 to April 2016 were randomly selected as wrist arthritis
      group, while 120 normal subjects were selected as normal control group. Venous
      blood was collected from all patients in normal control group and wrist arthritis
      group, respectively. Rheumatoid factor (RF), human C-reactive protein (CRP), and
      erythrocyte sedimentation rate (ESR) in venous blood were measured. The visual
      analogue scale (VAS) score was used to statistically analyze the pain of subjects
      in normal control and wrist arthritis groups; the wrist flexion and extension
      activities of subjects in normal control group and wrist arthritis group were
      measured. The expressions of CXCL13 and IL-24 mRNA in synovial tissue of normal
      control group and wrist arthritis group were detected by reverse transcription
      polymerase chain reaction (RT-PCR). Western blotting was used to detect the
      expressions of CXCL13 and IL-24 in normal control group and wrist arthritis
      group. RESULTS: The levels of CRP, RF, and ESR in the normal control group were
      within the normal range, but the levels of CRP, RF, and ESR in the wrist
      arthritis group were significantly higher than those in the normal control group.
      VAS scores and joint flexion extension activities in the normal control group
      were at normal levels. The VAS score of wrist arthritis group was significantly
      higher than that of the normal control group, and the joint flexion extension
      activities were significantly lower than that in the normal control group. The
      results of RT-PCR showed that the expression of CXCL13 mRNA in synovial tissue of
      wrist arthritis was significantly higher than that in the normal control group,
      while the expression of IL-24 mRNA in synovial tissue of wrist arthritis was
      significantly lower than that in normal control tissues. Western blotting showed
      that the expression of CXCL13 in synovial tissue of wrist arthritis was
      significantly higher than that in the normal control group, while the expression
      of IL-24 in synovial tissue of wrist arthritis was significantly lower than that
      in normal control groups. Analysis of variance showed that the expressions of
      CXCL13 and IL-24 in the normal control group and wrist arthritis group had
      statistically significant differences (p<0.01). CONCLUSIONS: The abnormal
      expressions of CXCL13 and IL-24 are closely related to the occurrence and
      development of wrist arthritis. This study shows that CXCL13 and IL-24 have
      important research values in wrist arthritis. CXCL13 and IL-24 expressions can be
      used as new indicators of the diagnosis and treatment of wrist arthritis.

PMID- 29364469
TI  - Estramustine phosphate induces prostate cancer cell line PC3 apoptosis by down
      regulating miR-31 levels.
AB  - OBJECTIVE: Prostate cancer seriously threats to patient's life and health.
      Estramustine phosphate (EP) is one of the most important drugs in the clinical
      treatment of prostate cancer. This study aims to explore the molecular mechanism
      of estramustine phosphate in regulating PC3 cell growth and survive through
      mediating miR-31. MATERIALS AND METHODS: Estramustine phosphate was used to treat
      prostate cancer cell line PC3. Flow cytometry was applied to detect PC3 cell
      growth and apoptosis. RT-PCR was performed to test miR-31 level. Prostate cancer
      tissue and paracarcinoma tissue were collected to test miR-31 level. PC3 cells
      were transfected with miR-31 or control microRNA by lipofectamine, and followed
      treated by estramustine phosphate. RESULTS: PC3 cell appeared growth restrain and
      apoptosis after treated by estramustine phosphate. MiR-31 level decreased after
      estramustine phosphate treatment. Prostate cancer tissue presented higher miR-31
      level than paracarcinoma tissue. MiR-31 over-expression inhibited estramustine
      phosphate induced PC3 cell apoptosis. CONCLUSIONS: Estramustine phosphate induces
      prostate cancer cell line PC3 apoptosis through reducing miR-31.

PMID- 29364470
TI  - Long noncoding RNA GIHCG is a potential diagnostic and prognostic biomarker and
      therapeutic target for renal cell carcinoma.
AB  - OBJECTIVE: Long noncoding RNA (lncRNA) GIHCG has been reported as an oncogene in
      hepatocellular carcinoma. However, the expression, roles, and clinical values of
      GIHCG in renal cell carcinoma (RCC) remain unclear. The aim of this study was to
      investigate the expression, roles, diagnostic and prognostic values of GIHCG in
      RCC. PATIENTS AND METHODS: The expression of GIHCG in 46 pairs of RCC tissues and
      adjacent normal renal tissues was measured by quantitative real-time polymerase
      chain reaction (qRT-PCR). GIHCG serum level in 46 RCC patients, 46 age- and sex
      matched healthy controls, 20 pre- and post-surgery RCC patients was measured by
      qRT-PCR. The diagnostic values of serum GIHCG were evaluated by receiver
      operating characteristic (ROC) curves analysis. The effect of GIHCG on RCC cell
      proliferation was evaluated using Cell Count Kit-8 assay, and the effect of GIHCG
      on RCC cell migration was evaluated using transwell migration assay. RESULTS:
      GIHCG is upregulated in RCC tissues compared with adjacent normal renal tissues.
      Increased expression of GIHCG is positively correlated with advanced TNM stages,
      Fuhrman grades, and poor prognosis. Serum GIHCG level is also significantly
      upregulated in RCC patients and correlated with advanced TNM stages. Serum GIHCG
      could accurately discriminate RCC patients from healthy controls, and also early
      stage RCC patients from healthy controls. Furthermore, serum GIHCG level is
      positively correlated with GIHCG expression in RCC tissues. Serum GIHCG level is
      significantly reduced after radical resection of RCC. Functional assays showed
      that knockdown of GIHCG significantly represses proliferation and migration of
      RCC cells. CONCLUSIONS: Long noncoding RNA GIHCG would sever as a novel
      diagnostic and prognostic biomarker and therapeutic target for RCC.

PMID- 29364471
TI  - Expression of three proteins in endometrioid adenocarcinoma and their
      significance in clinical nursing, diagnosis and treatment.
AB  - OBJECTIVE: This study aimed to investigate the role of NEDD9 (neural precursor
      cell expressed developmentally down-regulated 9), BCAR1/P130CAS (BCAR1/P130 Crk
      associated substrate) and paxillin in predicting the prognosis of endometrioid
      adenocarcinoma (EA), so as to guild the nursing of EA. PATIENTS AND METHODS: A
      total of 65 patients who visited Affiliated Hongqi Hospital of Mudanjiang Medical
      University between June 2015 and June 2017 were enrolled. They underwent
      gynecological surgery and had their EA confirmed by pathology, and they were
      assigned to the EA group. All EA tissues were sampled and archived in paraffin
      blocks. In addition, 40 specimens of atypical endometrial hyperplasia (EAH) (the
      EAH group) and 40 specimens of normal proliferative endometria with benign
      uterine fibroids (the EN group) were selected as controls. The protein levels of
      NEDD9, BCAR1/P130CAS, and paxillin in each group were then detected by
      immunohistochemical staining. RESULTS: The expression of the three proteins in
      the EA group and EAH group was significantly higher than that in the EN group,
      and their expression was significantly correlated with the clinical stage,
      histological grade and lymph node metastasis of EA. In addition, the expression
      of NEDD9, BCAR1/P130CAS, and paxillin in the EA group was positively correlated
      with each other. CONCLUSIONS: BCAR1/P130CAS and paxillin interact with NEDD9 to
      participate in the growth and migration of EA cells. Therefore, their proteins
      can be used as biomarkers for the diagnosis, treatment, and prognosis of EA.

PMID- 29364472
TI  - MiR-372-3p inhibits the growth and metastasis of osteosarcoma cells by targeting
      FXYD6.
AB  - OBJECTIVE: Growing evidence has suggested that dysregulation of miR-372-3p may
      contribute to tumor development and progression in various tumors. However, the
      function of miR-372-3p in osteosarcoma has not been investigated. In the present
      study, we aimed to study the effects of miR-372-3p on osteosarcoma cell
      proliferation and metastasis and its regulation on FXYD6. MATERIALS AND METHODS:
      The expression levels of miR-372-3p and FXYD6 mRNA were quantified by RT-PCR in
      human osteosarcoma cell lines and tissues. The effects of miR-372-3p up
      regulation on osteosarcoma cell proliferation and metastasis were assessed by
      MTT, wound healing assay and transwell assay. Finally, the potential regulatory
      effect of miR-372-3p on FXYD6 expression was confirmed. RESULTS: Our data showed
      that miR-372-3p was downregulated in osteosarcoma tissues compared with matched
      normal tissues, and the expression level of miR-372-3p was significantly lower in
      osteosarcoma cell lines in comparison with the normal human osteoblastic cell
      line. Transfection with the miR-372-3p mimic enhanced the osteosarcoma
      proliferation and metastasis. In vivo assay indicated that forced expression of
      miR-372-3p significantly suppressed tumor growth. Then, Bioinformatics prediction
      and experimental validation results confirmed that the function of miR-372-3p was
      achieved by targeting FXYD6 expression. CONCLUSIONS: Our findings revealed that
      miR-372-3p served as a tumor suppressor gene by targeting FXYD6 in osteosarcoma.
      Thus, miR-372-3 might be a potential therapeutic method for osteosarcoma.

PMID- 29364473
TI  - MiR-361 inhibits osteosarcoma cell lines invasion and proliferation by targeting
      FKBP14.
AB  - OBJECTIVE: MicroRNAs have been reported to contribute to the development of
      osteosarcoma via negatively regulating the target genes. Nevertheless, the
      undiscovered function of miR-361 on osteosarcoma development remains uncertain.
      PATIENTS AND METHODS: MiR-361 and FKBP14 (FK506-binding protein 14) expression in
      osteosarcoma samples were detected by Real-time polymerase chain reaction (PCR).
      Cells invasive ability was examined via the transwell invasion assay. The
      luciferase reporter assay was used to examine the regulation mechanism. The
      protein level of FKBP14 was detected by Western blot. Cell Counting Kit-8 (CCK-8)
      was used to detect cell lines proliferation. RESULTS: MiR-361 was reduced both in
      osteosarcoma samples and cell lines. Up-regulation of miR-361 significantly
      inhibited cells invasive and proliferative abilities, while down-regulation of
      miR-361 promoted cell lines invasion and proliferation. miR-361 could negatively
      regulate FKBP14 in osteosarcoma. Suppression of FKBP14 could reverse the function
      of miR-361 inhibitor. CONCLUSIONS: MiR-361 inhibits osteosarcoma cell lines
      invasion and proliferation by targeting FKBP14.

PMID- 29364474
TI  - The regulatory role of SLP-2 and mechanism on CCBE1 gene expression in rectal
      carcinoma and adjacent lymphatic tube tissues.
AB  - OBJECTIVE:   The incidence of rectal carcinoma (RC) has been increasing recently,
      and becomes the second most common digestive tumors besides gastric cancer, with
      a rise in the incidence of RC in younger populations. The early diagnosis and
      treatment are thus critical for the improvement of survival rate and life quality
      of patients. Stomatin-like protein 2 (SLP-2) is a type of membrane factor, which
      is generally found highly expressed in various tumors. Collagen and calcium
      binding EGF domain (CCBE1) belongs to lymphatic tube genesis factor. The
      regulatory role of SLP-2 gene on CCBE1 expression in RC tumor and adjacent
      lymphatic tube tissues, however, has not been studied. PATIENTS AND METHODS: 52
      RC patients were recruited, and tumor and adjacent lymphatic tube tissues were
      collected. Real-time PCR, western blotting and immunohistochemistry (IHC)
      staining were used to analyze SLP-2 and CCBE1 expressions. Human lymphatic
      endothelial cells (LECs) were cultured in vitro and were assigned to control,
      scramble, and SLP-2 siRNA group. MTT assay was used to detect cell proliferation,
      while caspase 3 activity was detected. RESULTS: SLP-2 and CCBE1 levels were
      significantly elevated in tumor lymphatic tissues, compared to that in adjacent
      tissues. Statistically positive correlation between SLP-1 and CCBE2 was found
      (p<0.05). The downregulation of SLP-2 by siRNA inhibited cell proliferation,
      elevated caspase3 activity, and decreased CCBE1 expression (p<0.05 compared to
      control group). CONCLUSIONS: SLP-2 is up-regulated in RC lymphatic tissues, and
      is positively correlated with the level of CCBE1, which provides the academic the
      basis for the development of medicine targeting SLP-2 in the anti-rectal
      carcinoma therapy.

PMID- 29364475
TI  - Formyl peptide receptor 2 mediated chemotherapeutics drug resistance in colon
      cancer cells.
AB  - OBJECTIVE: To determine the expression of formyl peptide receptor 2 (FPRL2) and
      its drug resistance role in cancer colon cells, and its underlying mechanisms.
      PATIENTS AND METHODS: The expression of FPRL2 and its legend (F2L) in colon
      cancer tissues or cancer cells was determined by immunohistochemistry assay and
      Real-time polymerase chain reaction (PCR), respectively. Chemosensitivity of 5-Fu
      and MMC in colon cancer cells were tested by cell counting kit-8 (CCK-8) method.
      Expression of p-ERK was determined by Western blot assay. RESULTS: The expression
      of FPRL2 and its legend was significantly higher in resistant colon cancer
      tissues than those in non-resistant colon cancer tissues. The FPRL2 positive
      cells were two-thirds in tested cell lines. All of cells were F2L positive. The
      IC50 (inhibitory concentration 50) by 5-Fu and MMC was significantly higher in
      FPRL2 positive cells than those negative cells. The expression of p-AKT was
      markedly increased in FPRL2 positive cells. Pretreatment with AKT inhibitor
      enhanced the drug-sensitivity of these cells to 5-Fu and MMC. CONCLUSIONS: The
      FPRL2 played a significant role in colon cancer drug resistance and this effect
      was through AKT pathway.

PMID- 29364476
TI  - MiRNA-155 promotes the invasion of colorectal cancer SW-480 cells through
      regulating the Wnt/beta-catenin.
AB  - OBJECTIVE: To investigate the role of microRNA-155 (miR-155) in the potential
      invasion of colon cancer cell and the underlying mechanism. PATIENTS AND METHODS:
      The expression level of miR-155 in colon cancer and adjacent normal tissues was
      detected by Real-time quantitative polymerase chain reaction (RT-PCR). miR-155
      mimics (miR-155), or siRNA against beta-catenin (beta-catenin siRNA), was
      transfected into human colon cancer cell line SW-480 using Lipofectamine 2000,
      respectively. RT-PCR was used to measure the expression levels of miR-155 and
      beta-catenin mRNA, and beta-catenin protein expression level was detected by
      Western blot. The in-vitro cell invasion abilities were determined by transwell
      invasion assays after up-regulating miR-155 or knocking down of beta-catenin.
      RESULTS: MiR-155 directly regulates beta-catenin at the transcriptional level,
      and promotes the invasion potential of colon cancer cell, at least partly through
      the upregulation of beta-catenin. CONCLUSIONS: The findings of this study suggest
      that miR-155 and beta-catenin may have a unique potential as a novel biomarker
      candidate for diagnosis and treatment of tumor metastasis.

PMID- 29364477
TI  - Long non-coding RNA DLEU7-AS1 promotes the occurrence and development of
      colorectal cancer via Wnt/beta-catenin pathway.
AB  - OBJECTIVE:   To investigate the expression features of long non-coding RNA
      (lncRNA) DLEU7-AS1 in colorectal cancer (CRC), so as to further study its role in
      the occurrence and development of CRC and its potential regulatory mechanism.
      PATIENTS AND METHODS: The expression levels of lncRNA DLEU7-AS1 in 82 pairs of
      CRC tissues and para-carcinoma normal tissues were detected via quantitative Real
      time polymerase chain reaction (qRT-PCR), and the correlation of DLEU7-AS1
      expression with pathological indexes of CRC and patients' prognosis was analyzed.
      Besides, the expression of DLEU7-AS1 in CRC cells was further detected via qRT
      PCR. The DLEU7-AS1 knockdown expression model was established using small
      interfering RNA in CRC cell lines HT-29 and HCT-116, and the effect of DLEU7-AS1
      on biological functions of CRC cells was analyzed via Cell Counting Kit-8 (CCK-8)
      and transwell invasion/migration assay. Finally, its potential mechanism was
      investigated via Western blotting. RESULTS: The results of qRT-PCR showed that
      the expression level of DLEU7-AS1 in CRC was significantly higher than that in
      normal tissues, and the difference was statistically significant. Compared with
      those in patients with low DLEU7-AS1 expression, the tumor stage in patients with
      high DLEU7-AS1 expression was higher, the prevalence rates of lymph node
      metastasis and distant metastasis were higher, and the overall survival rate was
      lower. Compared with those in the negative control group, the cell proliferation,
      invasion, and migration capacities were decreased significantly in DLEU7-AS1
      knockdown expression group. Moreover, the results of Western blotting revealed
      that the expressions of key proteins in Wnt/beta-catenin pathway, including beta
      catenin, c-myc, and cyclinD1, were decreased in si-DLEU7-AS1. CONCLUSIONS: The
      expression of DLEU7-AS1 is significantly increased in CRC, which is markedly
      associated with CRC staging, lymph node metastasis, distant metastasis and poor
      prognosis. DLEU7-AS1 may promote the proliferation, invasion and migration
      capacities of CRC through regulating the Wnt/beta-catenin pathway.

PMID- 29364478
TI  - Silencing of hsa_circ_0007534 suppresses proliferation and induces apoptosis in
      colorectal cancer cells.
AB  - OBJECTIVE: Although some circRNAs have been found to regulate the progression of
      colorectal cancer (CRC). However, their functions have not been completely
      clarified. In the present study, a novel circRNA hsa_circ_0007534 was
      investigated in CRC tumor tissues and cell lines. PATIENTS AND METHODS: The
      expression profile of circRNAs in CRC tumor tissues was performed by human
      circRNA microarray. The CCK-8 and apoptosis assay were measured in CRC cell lines
      after transfected with si-circRNA and si-NC. RESULTS: We analyzed a cohort of 33
      patients with CRC and demonstrated that the expression of hsa_circ_0007534 was
      significantly up-regulated in CRC tumor tissues as compared to adjacent non
      tumorous tissues. Moreover, hsa_circ_0007534 expression was correlated with tumor
      stage and lymph node metastasis. Furthermore, the silence of hsa_circ_0007534 by
      siRNA significantly inhibited proliferation and induced apoptosis of CRC cells.
      CONCLUSIONS: Hsa_circ_0007534 plays a crucial role in the initiation and
      progression of CRC and may be a potential therapeutic target of CRC.

PMID- 29364479
TI  - Targeting of GSK-3beta by miR-214 to facilitate gastric cancer cell proliferation
      and decrease of cell apoptosis.
AB  - OBJECTIVE: Wnt/beta-catenin pathway regulates cell proliferation and apoptosis.
      GSK-3beta degrades beta-catenin and negatively regulates Wnt/beta-catenin
      pathway. A previous study indicated that the GSK-3beta expression was
      significantly reduced in gastric cancer, along with the increase of miR-214
      expression. Bioinformatics analysis revealed complementary binding sites between
      miR-214 and 3'-UTR of GSK-3beta mRNA. This study investigated the regulatory role
      and related mechanism of miR-214 in the proliferation and apoptosis of gastric
      cancer cells. PATIENTS AND METHODS: Gastric cancer tissues were collected from
      patients and the expressions of miR-214, GSK-3beta and beta-catenin were
      determined. Dual luciferase reporter gene assay was used to study the regulatory
      role between miR-214 and GSK-3beta. Expressions of miR-214, GSK-3beta, beta
      catenin and survivin from GES-1 and MKN-28 cells were detected. Flow cytometry
      was used to measure cell proliferation and apoptosis. In vitro cultured MKN-28
      cells were treated with miR-214 inhibitor and/or pSicoR-GSK-3beta. Levels of GSK
      3beta, beta-catenin and survivin were detected, cell apoptosis was evaluated by
      flow cytometry and proliferation was tested by EdU staining. RESULTS: Compared to
      normal gastric mucosa, the levels of miR-214 and beta-catenin were elevated, and
      the expression of GSK-3beta was decreased in gastric cancer tissues. Compared to
      GES-1 cells, the expressions of miR-214, beta-catenin and survivin in MKN-28
      cells were upregulated, along with downregulation of GSK-3beta expression. The
      proliferation was enhanced whilst apoptosis was suppressed. After the
      transfection of miR-214 inhibitor and/or pSicoR-GSK-3beta, GSK-3beta expression
      was induced in MKN-28 cells while beta-catenin and survivin expressions were
      inhibited, along with the increase of cell apoptosis. CONCLUSIONS: MiR-214
      decreases GSK-3beta expression and promotes the pathogenesis of gastric cancer.
      The inhibition of miR-214 reduces the proliferation of gastric cancer cells via
      upregulation of GSK-3beta and suppression of Wnt/beta-catenin signal pathway,
      which provides fundamental support for the future therapy of gastric cancer.

PMID- 29364480
TI  - Correlation of CT indicators of NSCLC and pathological features and the
      expression level of p53 and c-myc.
AB  - OBJECTIVE: To investigate the correlations of the computed tomography (CT) signs
      of non-small cell lung cancer (NSCLC) with pathological features and the
      expression levels of phosphoprotein 53 (p53) and c-Myc in patients. PATIENTS AND
      METHODS: 87 patients with NSCLC admitted to the Department of Oncology in our
      hospital from July 2014 to March 2017 were randomly selected. Morphologies of
      NSCLC and cancer-adjacent tissues were detected by hematoxylin and eosin (H&E)
      staining; messenger ribonucleic acid (mRNA) and protein levels of p53 and c-Myc
      in cancer and cancer-adjacent tissues were detected using real-time polymerase
      chain reaction (RT-PCR) and immunohistochemistry (IHC); spiral CT (SCT) was
      conducted for exploring imaging signs of patients with NSCLC; the correlation of
      CT signs with pathology and the expressions of p53 and c-Myc was analyzed.
      RESULTS: H&E staining showed that NSCLC tissues had a larger nucleus, a larger
      nucleus-cytoplasm ratio, and a more evident histopathological atypia, with no
      clear histological structure compared with cancer-adjacent normal tissues; RT-PCR
      and IHC results revealed that the mRNA and protein expression levels of p53 and c
      Myc in NSCLC tissues were significantly higher than those in cancer-adjacent
      tissues, in which differences in mRNA levels were 1.75 folds and 1.84 folds,
      respectively (p<0.05). SCT signs indicated that swollen lymph nodes and
      spiculation, spinous process and deep lobulation signs often occurred in the
      chest of NSCLC patients, and pleural indentation appeared in the majority of
      patients; the chi-square test results showed that the positive rates of p53 and c
      Myc proteins were not related to pathological types of NSCLC, but significantly
      correlated with tumor differentiation (p<0.05); the positive rates of p53 and c
      Myc proteins were correlated with tumor diameter, spiculation and deep lobulation
      signs and lymph node metastasis (p<0.05), but not associated with spinous
      process, vacuole and pleural indentation signs (p>0.05). CONCLUSIONS: CT scan
      combined with the detection of p53 and c-Myc expressions can improve the
      diagnosis of lymph node metastasis and clinical staging for patients with NSCLC,
      which is conducive to the clinical treatment and prognosis analysis of NSCLC.

PMID- 29364481
TI  - Long non-coding RNA ASAP1-IT1 promotes cell proliferation, invasion and
      metastasis through the PTEN/AKT signaling axis in non-small cell lung cancer.
AB  - OBJECTIVE: To investigate the relative expression of long non-coding RNA (lncRNA)
      ASAP1-IT1 (hereafter called ASAP1-IT1) in tissues and cells of non-small cell
      lung cancer (NSCLC) patients, so as to explore the effect of ASAP1-IT1 on the
      biological effect of NSCLC cells. PATIENTS AND METHODS: Real-time quantitative
      polymerase chain reaction (qRT-PCR) was performed to detect the relative
      expressions of ASAP1-IT1 on tissues of 68 NSCLC patients and 5 cell lines.
      Besides, the interference sequence of ASAP1-IT1 was designed to detect the
      transfection efficiency through qRT-PCR experiment. Cell count kit 8 (CCK-8) and
      clone formation experiment were also carried out to determine the effect of ASAP1
      IT1 expression under interference on the proliferation ability of NSCLC cells. In
      addition, transwell experiment was also performed to investigate the effects of
      ASAP1-IT1 expression under interference on the invasion and metastasis of NSCLC
      cells. Furthermore, the Western blotting assay was also conducted to detect the
      downstream signal pathways through which ASAP1-IT1 regulated the biological
      behaviors of NSCLC. RESULTS: The results of qRT-PCR experiment showed that in 68
      NSCLC samples, upregulation of ASAP1-IT1 expression was identified in 51 samples
      (82.4%) in comparison with the expression in tumor-adjacent tissues, and a
      similar upregulation was also observed in 5 NSCLC cells. CCK-8 and clone
      formation experiments also revealed that interference on ASAP1-IT1 expression
      could inhibit the proliferation of NSCLC cells, while the transwell experiment
      showed that the interference on ASAP1-IT1 expression could block the migration
      and invasion ability of NSCLC cells. The results of Western blotting assay also
      indicated that ASAP1-IT1 could regulate the biological behaviors of NSCLC cells
      through phosphatase and tensin homolog deleted on chromosome ten (PTEN)/serine
      threonine kinase (AKT) pathway. CONCLUSIONS: In this study, it was found that the
      expression of ASAP1-IT1 is relatively upregulated in NSCLC cells and tissues,
      which can promote the proliferation, invasion and metastasis of NSCLC cells
      through regulating the PTEN/AKT signal pathway. Thus, the therapeutic target of
      ASAP1-IT1 is expected to provide important ideas for reversing the malignant
      phenotype of NSCLC in clinical practice.

PMID- 29364483
TI  - Regulation of DNA methylation and tumor suppression gene expression by miR-29b in
      leukemia patients and related mechanisms.
AB  - OBJECTIVE: Leukemia is characterized as a kind of malignant clonal disease in
      hematological stem cells. The study showed an abnormal level of DNA methylation
      in leukemia cells, which further led to an abnormal expression of hematological
      genes. This study investigated the role of miR-29b on the modulation of DNA
      methylation and tumor suppressor gene expression in leukemia patients. PATIENTS
      AND METHODS: A total of 21 leukemia patients were recruited for the collection of
      monocytes. Methylation levels of promoter sequence of ESR1 and p15 genes were
      analyzed by methylation assay kit combined with DHPLC. DNA microarray and qRT-PCR
      were used to measure microRNA expressional profile, and bioinformatics plus
      luciferase reporter assay confirmed target gene of miR-29b. After transfection
      with miR-29b, promoter methylation levels of ESR1 and p15 gene were measured.
      Protein expressions of DNMT1 DNA (cytosine-5)-methyltransferase 1 (DNMT1), DNA
      (cytosine-5)-methyltransferase 3A (DNMT3A) and DNA (cytosine-5)-methyltransferase
      3B (DNMT3B) were quantified. RESULTS: The methylation levels of the promoter
      region of ESR1 and p15 genes in monocytes of leukemia patient were significantly
      elevated (p < 0.05). DNA microarray and qRT-PCR confirmed the down-regulation of
      miR-29b (p < 0.05). Luciferase reporter assay revealed DNMT1, DNMT3A and DNMT3B
      as target genes of miR-29b. MiR-29b transfection inhibited the expressions of
      DNMT3A and DNMT3B in Kasumi-1 cells (p < 0.05), and promoter methylation levels
      of estrogen Receptor 1 (ESR1) and p15 gene were decreased (p < 0.05).
      CONCLUSIONS: In leukemia cells, hyper- methylation existed in the promoter region
      of tumor suppressor gene. The methylation was enhanced in gene DNMT1, DNMT3A and
      DNMT3B via the reduction of miR-29b in leukemia tumor cells.

PMID- 29364482
TI  - MiR-101 promotes nasopharyngeal carcinoma cell apoptosis through inhibiting
      Ras/Raf/MEK/ERK signaling pathway.
AB  - OBJECTIVE: Extra-cellular signal regulated kinase (ERK)/mitogen activated protein
      kinase (MAPK) signaling pathway is widely involved in cell proliferation and
      apoptosis. MAPK kinase 1 (MEK1) is the upstream protein kinase of ERK that can
      activate ERK/MAPK signaling pathway. microRNA-101 (MiR-101) down-regulation is
      found to be associated with nasopharyngeal carcinoma (NPC) pathogenesis.
      Bioinformatics analysis shows the complementary targeted relationship between miR
      101 and the 3'-UTR of MEK1 mRNA. This study explores the role of miR-101 in
      regulating MEK1 expression, ERK/MAPK signaling pathway activation, and NPC
      pathogenesis. MATERIALS AND METHODS: Dual luciferase assay confirmed the targeted
      relationship between miR-101 and MEK1. MiR-101 and MEK1 expressions were compared
      in inflammatory nasopharynx tissue and NPC tissue. MiR-101, MEK1, phosphorylated
      ERK 1/2 (p-ERK1/2), survivin expressions in NP69, CNE-1, HONE1, and C666-2 cell
      lines were detected. NPC cell line C666-1 was cultured in vitro and divided into
      four groups, including miR-NC, miR-101, si-NC and si-MEK1. Cell apoptosis was
      determined by flow cytometry. Cell proliferation was evaluated by EdU staining.
      RESULTS: MiR-101 targeted inhibited MEK1 expression. MiR-101 was significantly
      down-regulated, while MEK1 was significantly elevated in NPC tissue compared with
      inflammatory nasopharynx tissue. MiR-101 was markedly declined, whereas MEK1, p
      ERK1/2, and survivin were apparently increased in CNE-1, HONE1, and C666-1 cells
      compared with NP69 cells. MiR-101 mimic and/or si-MEK1 transfection significantly
      reduced MEK1, p-ERK1/2, and survivin levels, attenuated cell proliferation, and
      enhanced cell apoptosis. CONCLUSIONS: Down-regulation of miR-101 was related to
      NPC pathogenesis. MiR-101 elevation suppressed NPC cell proliferation and
      promoted apoptosis through targeted inhibiting MEK1 expression to alleviate
      ERK/MAPK signaling pathway and survivin expression.

PMID- 29364484
TI  - Silencing of LncRNA TCONS_00088786 reduces renal fibrosis through miR-132.
AB  - OBJECTIVE: To examine the role of long non-coding ribonucleic acid (LncRNA)
      TCONS_00088786 in the development of renal interstitial fibrosis and its
      potential mechanism in this process. MATERIALS AND METHODS: Unilateral ureteral
      obstruction (UUO) was used to induce tubulointerstitial fibrosis. Masson staining
      showed the degree of renal fibrosis in UUO mice. Immunohistochemistry and
      immunofluorescence were performed to detect the fibrosis-related proteins, the 24
      h urine volume and protein content. The renal functions were reflected via serum
      creatinine (Scr) and blood urea nitrogen (BUN). Changes in lncRNATCONS_00088786,
      miR-132 and collagen I and III in the development process of renal fibrosis were
      detected through reverse transcription-polymerase chain reaction (RT-PCR). Small
      interfering RNA (siRNA) was transfected into NRK52E cells to mimic the knockdown.
      Western blot was adopted to detect the changes in miR-132, collagen I and III
      after the siRNA was transfected by transforming growth factor-beta (TGF-beta) for
      24 h. RESULTS: With the development of renal fibrosis, lncRNA TCONS_00088786 and
      miR-132 were increased gradually. After the knockdown of lncRNA TCONS_00088786,
      miR-132 was decreased and fibrosis-related protein was also decreased.
      CONCLUSIONS: Decreased lncRNA TCONS _00088786 inhibits renal interstitial
      fibrosis by reducing miR-132 and it may be a potential novel molecular target for
      the treatment of renal interstitial fibrosis.

PMID- 29364485
TI  - FGF23 promotes renal interstitial fibrosis by activating beta-catenin.
AB  - OBJECTIVE: To investigate the role and mechanism of fibroblast growth factor 23
      (FGF23) in renal interstitial fibrosis. MATERIALS AND METHODS: Rat renal tubular
      epithelial cell line (NRK-52E) was selected for in vitro experiments. Effect of
      FGF23 on extracellular matrix was observed. High expression of FGF23 was induced
      by injecting the plasmid into the caudal vein. The model of unilateral ureteral
      obstruction (UUO) was established for in vivo experiments. RESULTS: FGF23
      increased the expression of extracellular matrix proteins FN, alpha-SMA and Type
      1 collagen of NRK-52E induced by TGFbeta1, while FGF23 increased the expression
      of p-beta-catenin 675. In UUO model mice, fibrosis in the FGF23 high expression
      group increased significantly compared to that of the control group. Meanwhile,
      beta-catenin signal was activated. CONCLUSIONS: FGF23 can promote the deposition
      of extracellular matrix of NRK-52E induced by TGFbeta1 in vitro. It aggravated
      the degree of renal interstitial fibrosis in UUO model, which is related to the
      activation of beta-catenin signaling pathway.

PMID- 29364486
TI  - Dexamethasone alleviates allergic asthma immature rat through Toll like receptor
      4.
AB  - OBJECTIVE: The allergic asthma model induced by ovalbumin (OVA) was established
      in the immature rat. Dexamethasone (DXM) was adopted for intervention to analyze
      the treatment effect and to explore the relationship with toll-like receptor 4
      (TLR4). MATERIALS AND METHODS: Immature SD rat was treated by OVA to construct
      allergic asthma model and intervened by DXM. The rats were randomly divided into
      model group, experimental group, and control group. The changes in lung tissue
      were observed by light microscope. The EOS infiltration and reactivity of airway
      wall were compared. The expressions of TLR2 and TLR4 protein and mRNA in the lung
      tissue were tested by Western blot and RT-PCR. RESULTS: The lung tissue in the
      model group was infiltrated by a lot of inflammatory cells, and mucous membrane
      edema was observed, compared with that in the control group. There were only a
      few inflammatory cells in the interstitial tissue and pulmonary alveoli in the
      experimental group compared with that in the model group. EOS count of airway
      wall and airway reactivity decreased in the experimental group. The levels of
      TLR2 and TLR4 were significantly elevated in the third week compared with the
      first week (p<0.05). CONCLUSIONS: The treatment of DXM can alleviate the
      pathological changes of the lung tissue in SD immature rat with allergic asthma,
      reduce EOS infiltration in the airway wall, decrease airway reactivity, and
      elevate expressions of TLR2 and TLR4.

PMID- 29364487
TI  - Prophylactic use of non-invasive mechanical ventilation in lung resection.
AB  - OBJECTIVE: To evaluate if the prophylactic application of BiPAP previous to lung
      resection and 17 hours postoperatively improves respiratory function. In order to
      do this, we studied the results of arterial blood gases and portable spirometry
      in the immediate postoperative period and at the first and third postoperative
      day. Secondary objectives included evaluating whether this same pattern decreases
      the incidence of postoperative pulmonary complications (PPC) and hospital stay.
      PATIENTS AND METHODS: This was a prospective, randomized clinical study. Between
      January 2012 and June 2013, 50 patients who had undergone lung resection with
      posterolateral thoracotomy were assigned to one of two groups by a random number
      generator according to whether or not they would receive prophylactic BiPAP pre-
      and postoperatively. RESULTS: The results of the gasometric and spirometric
      values were similar in both groups. There were no statistically significant
      differences (p > 0.05). There was not a decrease in the incidence of PPC in the
      group that received prophylactic BiPAP. Likewise, postoperative stay was similar
      in both groups. The BiPAP group was 6.60 +/- 4 days and the non BiPAP group was
      6.84 +/- 3.94 days (p = 0.63). CONCLUSIONS: One drawback of this work was the
      limited number of hours that BiPAP was employed, and when compared to other
      studies, the application of low-pressure support. We did not find any significant
      differences between using prophylactic BiPAP or not, suggesting that such
      treatment should not be performed indiscriminately. More investigations are
      needed with a larger number of patients in order to better evaluate the possible
      benefits of using prophylactic BiPAP in thoracic surgery.

PMID- 29364488
TI  - Physical inactivity induces the atrophy of skeletal muscle of rats through
      activating AMPK/FoxO3 signal pathway.
AB  - OBJECTIVE: Long-term physical inactivity can cause the atrophy of skeletal
      muscle. The aim of this study is to explore the underlying mechanisms of physical
      inactivity-induced atrophy of skeletal muscle. MATERIALS AND METHODS: 14 Sprague-
      Dawley (SD) male rats were divided into 2 groups including normal control (NC)
      and hindlimb suspension (HS) groups. After two weeks of HS stimulation, the ratio
      between skeletal muscle weight and body weight, and cross-sectional area (CSA) of
      skeletal muscle fibers, were measured. Western blot was applied to evaluate the
      expression of proteins associated with atrophy and autophagy. The transmission
      electron microscope was used to observe the ultra-microstructure and the
      mitochondrial quality of skeletal muscle. RESULTS: The rats subjected to 2-week
      HS treatment presented an evident atrophy of the skeletal muscle with a
      significantly reduced ratio between skeletal muscle weight and body weight, and
      smaller cross-sectional area (CSA) of skeletal muscle fibers when compared with
      control rats. Meanwhile, HS stimulation resulted in the damage of mitochondria,
      the increased expression of MuRF1 and Atrogin-1/MAFbx, and enhanced apoptosis, as
      well as dysfunctional autophagy in skeletal muscle. CONCLUSIONS: HS-induced
      skeletal muscle atrophy involves the activation of AMPK/FoxO3 signal pathway,
      evidenced as AMPK phosphorylation, FoxO3 activation, and Atrogin-1 and MuRF1 up
      regulation. FoxO3-mediated autophagy plays an important regulatory role in HS
      induced skeletal muscle atrophy.

PMID- 29364489
TI  - Transnasal sphenopalatine ganglion blockade for acute facial pain: a prospective
      randomized case-control study.
AB  - OBJECTIVE: Long-term physical inactivity can cause the atrophy of skeletal
      muscle. The aim of this study is to explore the underlying mechanisms of physical
      inactivity-induced atrophy of skeletal muscle. MATERIALS AND METHODS: 14 Sprague-
      Dawley (SD) male rats were divided into 2 groups including normal control (NC)
      and hindlimb suspension (HS) groups. After two weeks of HS stimulation, the ratio
      between skeletal muscle weight and body weight, and cross-sectional area (CSA) of
      skeletal muscle fibers, were measured. Western blot was applied to evaluate the
      expression of proteins associated with atrophy and autophagy. The transmission
      electron microscope was used to observe the ultra-microstructure and the
      mitochondrial quality of skeletal muscle. RESULTS: The rats subjected to 2-week
      HS treatment presented an evident atrophy of the skeletal muscle with a
      significantly reduced ratio between skeletal muscle weight and body weight, and
      smaller cross-sectional area (CSA) of skeletal muscle fibers when compared with
      control rats. Meanwhile, HS stimulation resulted in the damage of mitochondria,
      the increased expression of MuRF1 and Atrogin-1/MAFbx, and enhanced apoptosis, as
      well as dysfunctional autophagy in skeletal muscle. CONCLUSIONS: HS-induced
      skeletal muscle atrophy involves the activation of AMPK/FoxO3 signal pathway,
      evidenced as AMPK phosphorylation, FoxO3 activation, and Atrogin-1 and MuRF1 up
      regulation. FoxO3-mediated autophagy plays an important regulatory role in HS
      induced skeletal muscle atrophy.

PMID- 29364490
TI  - Intranasal drug administration for procedural sedation in children admitted to
      pediatric Emergency Room.
AB  - OBJECTIVE: Pain relief is a very important aspect in Pediatrician's clinical
      practice. It is often thought that young children, particularly infants, do not
      perceive as much pain as adults because of their immature nervous system and that
      untreated pain would not have adverse long-term consequences. Instead, it has
      been demonstrated that infants and children experience pain in a similar manner
      to adults. Many factors, particularly emotional factors, can increase the child's
      pain perception. Children live with anxiety even minor procedures. This suggests
      the need for an adequate sedation and the way of sedation should be free of pain
      itself. We believe the route to be followed may be the intranasal (IN)
      administration of sedative drugs. MATERIALS AND METHODS: We have conducted a
      brief review of the literature by Pubmed about the most commonly used sedative
      drugs: sufentanyl, fentanyl, midazolam, ketamine, nitrous oxide and
      dexmedetomidine. We have investigated in the literature the type of
      administration of IN drugs: drop instillation or by a mucosal atomizer device
      (MAD). RESULTS: In our study, it was noted that IN drugs administration is an
      effective and safe method to reduce anxiety and to deliver analgesia because it
      is practical and non-invasive. Moreover, therapeutic levels of sedatives are low
      due to the presence of a rich vascular plexus in the nasal cavity, which
      communicates with the subarachnoid space via the olfactory nerve and reduce the
      time of medication delivery, that is, the onset of action. The use of MAD even
      gives as better bioavailability of drugs. CONCLUSIONS: IN sedation via MAD is
      effective and safe and should be one of the first choices for procedural sedation
      in children.

PMID- 29364491
TI  - Preventive effects of low molecular weight heparin on formation of deep vein
      thrombosis by reducing D dimer values in patients undergoing spinal surgery.
AB  - OBJECTIVE: Deep vein thrombosis (DVT) is one of the most common complications for
      patients undergoing spinal surgery. This study aims to investigate preventive
      effects of low-molecular-weight heparin (LMWH) on the formation of DVT. PATIENTS
      AND METHODS: This study involved 37 patients who underwent spinal surgery between
      April 2016 and April 2017. Patients were divided into LMWH group and Control
      group. Clinical parameters, including operation time, intra-operative blood loss,
      incision length, post-operative visual analogue scale (VAS), exercise-time
      leaving bed and post-operative extubation time, were collected. Blood routine
      analysis, including platelet count (PLT), red blood cell count (RBC), white blood
      cell count (WBC) and hemoglobin (HGB) were also conducted. Coagulation
      parameters, including prothrombin time-international normalized ratio (PT-INR),
      fibrinogen (FIB), activated partial thromboplastin time (APTT), thrombin time
      (TT), prothrombin time 1 (PT-1) and D-dimer (DD), were evaluated. The drainage
      fluid was collected. RESULTS: LMWH treatment significantly decreased operative
      time, blood loss and incision length compared to Control group at 1st, 3rd and
      7th day post-operation (all p<0.05). LMWH treatment significantly increased WBC
      levels compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05).
      LMWH treatment significantly decreased DD levels in the post-operative patients
      compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05).
      However, LMWH treatment doesn't affect drainage amounts of patients. DD levels
      were positively correlated with WBC counts for the LMWH treated patients.
      CONCLUSIONS: Low molecular weight heparin effectively prevents the formation of
      DVT by reducing DD values in patients undergoing spinal surgery.

PMID- 29364492
TI  - Rosuvastatin inhibits inflammatory response and resists fibrosis after myocardial
      infarction.
AB  - OBJECTIVE: To study the effect of rosuvastatin on myocardial infarction in rats
      and its mechanism of action. MATERIALS AND METHODS: 24 Sprague-Dawley (SD) rats
      were randomly divided into 3 groups: intensive statin group (n=8), myocardial
      infarction control group (n=8) and sham-operation group (n=8). The left anterior
      descending coronary artery was ligated to establish myocardial infarction models.
      Rats in intensive statin group were treated with gavage via rosuvastatin (1 mg *
      kg) and 1.5 mL distilled water suspension at 3 d before operation, while rats in
      the other two groups received gavage via the same amount of distilled water till
      4 weeks after operation. Venous blood was collected using capillary glass tubes
      at 3 d before operation (before medication) and the last day in the 4th week
      after operation. Interleukin-6 (IL-6) was detected via chemiluminescence assay,
      and tumor necrosis factor-alpha (TNF-alpha) was detected via immunofluorescence
      assay. Hematoxylin and eosin (HE) staining and Masson staining were performed for
      myocardium to detect the inflammation and fibrosis. Finally, the expressions of
      inflammatory protein p65, peroxisome proliferator-activated receptor (PPAR) and
      fibrin were detected via Western blotting, and the Snail expression was detected
      by immunohistochemical assay. RESULTS: The survival rate and cardiac function of
      rats in intensive statin group were superior to those in control group. HE
      staining and detection of blood IL-6 and TNF-alpha, and p65 and PPAR protein
      expressions revealed that the inflammatory levels in the body and myocardium of
      rats in intensive statin group were decreased compared with those in control
      group. Masson staining and detection of fibrin level showed that the myocardial
      fibrosis level of rats in intensive statin group was reduced compared with that
      in control group. CONCLUSIONS: Rosuvastatin can reduce the level of myocardial
      fibrosis through alleviating the inflammatory response in rats with myocardial
      infarction.

PMID- 29364493
TI  - Is ovulation induction with letrozole in breast cancer patients still safe even
      if it could increase progesterone levels?
AB  - Very high progesterone levels (mean 186.6 +/- 43.6 ng/mL) during the luteal phase
      were found in a small study of breast cancers patients undergoing controlled
      ovarian stimulation (COS) with letrozole plus recombinant FSH. Results highlight
      the need to further evaluate this in larger series. While waiting, the clinical
      significance of high progesterone levels can be drawn from epidemiological and
      experimental data here reviewed in order to give reassurance to the clinician
      involved in fertility preservation. If the progesterone increase will be
      confirmed, epidemiological and experimental data do not seem to indicate a
      detrimental effect or they could even be protective. As this possible rise of
      levels is a very short event in the very long lasting and multifactorial breast
      carcinogenesis, it is unlikely that it will significantly influence breast cancer
      prognosis.

PMID- 29364494
TI  - Oxcarbazepine causes neurocyte apoptosis and developing brain damage by
      triggering Bax/Bcl-2 signaling pathway mediated caspase 3 activation in neonatal
      rats.
AB  - OBJECTIVE: Anti-epileptic drugs (AEDs) are the main methods for treatment of
      neonatal seizures; however, a few AEDs may cause developing brain damage of
      neonate. This study aims to investigate effects of oxcarbazepine (OXC) on
      developing brain damage of neonatal rats. MATERIALS AND METHODS: Both of neonatal
      and adult rats were divided into 6 groups, including Control, OXC 187.5 mg/kg,
      OXC 281.25 mg/kg, OXC 375 mg/kg group, LEV and PHT group. Body weight and brain
      weight were evaluated. Hematoxylin and eosin (HE) and Nissl staining were used to
      observe neurocyte morphology and Nissl bodies, respectively. Apoptosis was
      examined using TUNEL assay, and caspase 8 activity was evaluated using
      spectrophotometer method. Cytochrome C-release was evaluated using flow
      cytometry. Western blot was used to examine Bax and Bcl-2 expression. RESULTS:
      OXC 375 mg/kg treatment significantly decreased brain weight compared to Control
      group in neonatal rats (P5 rats) (p<0.05). OXC administration causes histological
      changes of neurocytes. OXC 281.25 mg/kg or more concentration significantly
      decreased neurocytes counts and increased TUNEL-staining positive neurocytes
      compared to Control group (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg
      significantly increased caspase 3 activity compared to Control group in P5 rats
      (p<0.05). OXC 281.25 mg/kg and OXC 375 mg/kg significantly increased Bax, Bax/Bcl
      2 ratio and cytochrome C release in frontal lobes compared to Control group in P5
      rats (p<0.05). CONCLUSIONS: Oxcarbazepine at a concentration of 281.25 mg/kg or
      more causes neurocyte apoptosis and developing brain damage by triggering Bax/Bcl
      2 signaling pathway mediated caspase 3 activation in neonatal rats.

PMID- 29364495
TI  - New evidence on oral L. plantarum P17630 product in women with history of
      recurrent vulvovaginal candidiasis (RVVC): a randomized double-blind placebo
      controlled study.
AB  - OBJECTIVE: To evaluate activity and tolerability of an oral product containing
      the specific probiotic strain Lactobacillus plantarum P17630 on vaginal
      colonization of lactic acid bacteria. PATIENTS AND METHODS: L. plantarum P17630
      (5x109 CFU/capsule) or placebo were formulated in capsules and administrated
      orally to a total of 93 women with a history of recurrent vulvovaginal
      candidiasis over a period of 3 treatment cycles (15 days/cycle) separated by 15
      day wash-out intervals. Vulvovaginal examinations and vaginal mycological
      culture, including Nugent score and Lactobacillary grade (LBG), were assessed at
      baseline, at day 45 and at day 90 (end of the study). RESULTS: Probiotic intake
      significantly improved lactobacilli colonization on vaginal epithelial cells. The
      results demonstrated a significant difference in LBG score when comparing day 0
      to day 45 (p=0.000016) and to day 90 (p=0.001415) in women treated with L.
      plantarum P17630. No evidence of improvement in LBG score was recorded in women
      who received placebo (p<0.005). The increased lactobacilli adhesion was
      associated with the improvement of clinical signs such as redness, swelling, and
      discharge. CONCLUSIONS: This study demonstrates that the administration of oral
      probiotic Lactobacillus plantarum P17630 improves vagina colonization of acid
      lactic bacteria (an increase of vaginal LBG score) and suggests the use of this
      oral product to successfully prevent episodes of vulvovaginal candidiasis. The
      clinical study described in this article is registered in the ISRCTN registry
      with trial registration ID ISRCTN12669692.

PMID- 29364496
TI  - Biological function of microRNA-30c/SOX9 in pediatric osteosarcoma cell growth
      and metastasis.
AB  - OBJECTIVE: Osteosarcoma is one of the commonest malignant bone tumors, which
      frequently occurs in children all over the world. To find out methods to improve
      the therapeutic effect of osteosarcoma, it is necessary to detect the functioning
      mechanism of miR-30c to regulate the proliferation and metastasis of osteosarcoma
      cell. PATIENTS AND METHODS: In order to reveal the expression level of miR-30c,
      quantitative Real-time PCR (qRT-PCR) method was chosen. To evaluate cell
      viability and proliferation rates, colony formation and cell counting kit-8
      (CCK8) assay were introduced. Based on cell migration and invasion assay,
      metastasis capacity of breast cancer cells was studied. Protein levels were
      measured by Western blotting assay and cell cycle distribution was identified by
      flow cytometry. Bioinformatics analysis and Luciferase assay were used to predict
      and verify the target gene. RESULTS: Compared with pericarcinomatous tissues
      (n=38), miR-30c in osteosarcoma tissues was significantly suppressed.
      Overexpressed miR-30c could weaken osteosarcoma cell's abilities of viability,
      proliferation, migration and invasion. Moreover, it could also encourage
      osteosarcoma cell apoptosis and block cell cycle at G0/G1 phase. According to
      bioinformatics analysis and Luciferase reporter assay, SOX9 was recognized as the
      target gene of miR-30c. Restoration of SOX9 could make miR-30c regain the ability
      of suppression on tumorigenesis of osteosarcoma cells. CONCLUSIONS: MiR-30c could
      play an important role in tumor suppression for pediatric osteosarcoma
      development and metastasis by targeting SOX9 in vitro. Thus, a creative and
      potential target was provided for diagnosis and treatment of osteosarcoma.

PMID- 29364497
TI  - Curative efficacy of penehyclidine combined with edaravone on acute cerebral
      infarction and their effects on serum TNF-alpha and NDS score in rats.
AB  - OBJECTIVE: To investigate the effects of penehyclidine combined with edaravone on
      acute cerebral infarction (ACI) in rats. MATERIALS AND METHODS: A rat model of
      middle cerebral artery infarction was created. The rats were randomly divided
      into sham, model and treatment group. After grouping, rats in the treatment
      groups were treated with edaravone combined with phenecyclidine. The rats in the
      sham and model group were given an equal volume of phosphate-buffered saline
      (PBS). The therapeutic effects on rats at 3 d and 7 d after treatment were
      observed, the levels of serum TNF-alpha, interleukin-6 (IL-6) and high-mobility
      group box 1 protein (HMGB1) before and after treatment were compared, and the NDS
      scores were recorded. RESULTS: After treatment, the effective rate in treatment
      groups was higher than that in control group. The expression levels of serum TNF
      alpha, HMGB1 and IL-6 in treatment groups showed gradually decreasing trends
      after treatment, and there were significant differences in the levels before and
      after treatment (p<0.05). At 3 d, the decrease ranges of expression levels of TNF
      alpha, HMGB1, and IL-6 in model and treatment groups were larger than those in
      control group; there were statistically significant differences in the expression
      levels between the two groups (p<0.05). The NDS score was gradually decreased
      after treatment, while the activities of daily living (ADL) score were gradually
      increased after treatment. There were significant differences in the scores
      between the two groups at each time point (p<0.05). There were positive
      correlations of the expression levels of serum IL-6 and HMGB1 with the expression
      level of TNF-alpha (correlation coefficient=0.8731 and 0.9084, p<0.01), and there
      was also a positive correlation between the TNF-alpha level and the NDS score
      (correlation coefficient=0.8331, p<0.01). CONCLUSIONS: Penehyclidine combined
      with edaravone has a better clinical treatment effect on ACI rats, which can
      significantly reduce the levels of serum TNF-alpha, IL-6 and HMGB1 and the NDS
      score, so it is worthy of popularization in clinical application.

PMID- 29364498
TI  - Synthetic cathinones related fatalities: an update.
AB  - OBJECTIVE: Synthetic cathinones, more commonly known as "bath salts", are
      synthetic drugs chemically related to cathinone, a psychostimulant found in the
      khat plant. They are the first most consumed products among new psychoactive
      substances, which cause psychostimulant and hallucinogenic effects determining a
      number of fatalities worldwide.  In this paper, we have systematically reviewed
      cases of synthetic cathinones-related fatalities analytically confirmed, which
      have occurred in the last few years. MATERIALS AND METHODS: Relevant scientific
      articles were identified in Medline, Cochrane Central, Scopus, Web of Science and
      Institutional/government websites up to November 2017 using the following
      keywords: synthetic cathinones, mephedrone, methylenedioxypyrovalerone, MDPV,
      methylone, ethylone, buthylone, fatal intoxication, fatalities and death.
      RESULTS: In total, 20 citations met the criteria for inclusion, representing
      several fatal cases with analytically confirmed synthetic cathinones in
      biological sample/s of the deceased. The death was attributed to hyperthermia,
      hypertension, cardiac arrest and more in general to the classic serotonin
      syndrome. Only rarely did the concentration of the parent drug causing fatality
      overcome the value of 1 mg/L in post-mortem biological fluids. CONCLUSIONS: Abuse
      of synthetic cathinones still represents a serious public health issue.
      Systematic clinical studies on both the animal and human model are lacking;
      therefore, the only available data are from the users who experience the possible
      hazardous consequences. Analytical methodologies for the identification of parent
      compounds and eventual metabolites both in ante-mortem and post-mortem cases need
      to be developed and validated. Analytical data should be shared through different
      communication platforms with the aim of stopping this serious health threat for
      drug users.

PMID- 29364499
TI  - Toll-like receptors and radiation protection.
AB  - Exposure to ionizing radiation (IR) causes severe injuries to the human body, and
      normal tissue toxicity also limits the further application of cancer
      radiotherapy. However, current clinically used radioprotective agents are
      difficult to produce satisfactory effects. Toll-Like receptor (TLR) is a kind of
      pattern recognition receptor (PRR) that has been extensively studied for
      radioprotection in recent years. Several TLR family members are closely related
      to radioprotection. In cultured cells, TLR2, TLR5 or TLR9 agonist was proved to
      inhibit radiation-induced apoptosis and increase cell survival. TLR5 ligand
      CBLB502 was reported to alleviate bone marrow and intestinal injuries in mice and
      rhesus monkeys. Activation of TLR4 by its agonist LPS can protect bone marrow
      damage and lower mice mortality after irradiation. TLR9 ligand also exhibited
      protective effects on mid jejunum. Moreover, some kinds of TLR agonists, such as
      TLR2/6 co-agonist CBLB613, were reported to be more effective in radioprotection
      than single TLR agonist. In conclusion, TLRs and their ligands provide novel
      strategies for radiation protection in nuclear accidents as well as protection of
      normal tissues during cancer radiotherapy.

PMID- 29364500
TI  - Autosomal-dominant myopia associated to a novel P4HA2 missense variant and
      defective collagen hydroxylation.
AB  - We recently described a complex multisystem syndrome in which mild-moderate
      myopia segregated as an independent trait. A plethora of genes has been related
      to sporadic and familial myopia. More recently, in Chinese patients severe myopia
      (MYP25, OMIM:617238) has been linked to mutations in P4HA2 gene. Seven family
      members complaining of reduced distance vision especially at dusk underwent
      complete ophthalmological examination. Whole-exome sequencing was performed to
      identify the gene responsible for myopia in the pedigree. Moderate myopia was
      diagnosed in the family which was associated to the novel missense variant
      c.1147A > G p.(Lys383Glu) in the prolyl 4-hydroxylase,alpha-polypeptide 2 (P4HA2)
      gene, which catalyzes the formation of 4-hydroxyproline residues in the collagen
      strands. In vitro studies demonstrated P4HA2 mRNA and protein reduced expression
      level as well as decreased collagen hydroxylation and deposition in mutated
      fibroblast primary cultures compared to healthy cell lines. This study suggests
      that P4HA2 mutations may lead to myopic axial elongation of eyeball as a
      consequence of quantitative and structural alterations of collagen. This is the
      first confirmatory study which associates a novel dominant missense variant in
      P4HA2 with myopia in Caucasian patients. Further studies in larger cohorts are
      advisable to fully clarify genotype-phenotype correlations.

PMID- 29364501
TI  - WNT10B mutations associated with isolated dental anomalies.
AB  - Isolated hypodontia is the most common human malformation. It is caused by
      heterozygous variants in various genes, with heterozygous WNT10A variants being
      the most common cause. WNT10A and WNT10B are paralogs that likely evolved from a
      common ancestral gene after its duplication. Recently, an association of WNT10B
      variants with oligodontia (severe tooth agenesis) has been reported. We performed
      mutational analysis in our cohort of 256 unrelated Thai families with various
      kinds of isolated dental anomalies. In 7 families afflicted with dental anomalies
      we detected 4 heterozygous missense variants in WNT10B. We performed whole exome
      sequencing in the patients who had WNT10B mutations and found no mutations in
      other known hypodontia-associated genes, including WNT10A, MSX1, PAX9, EDA,
      AXIN2, EDAR, EDARADD, LPR6, TFAP2B, LPR6, NEMO, KRT17, and GREM2. Our findings
      indicate that the variants c.475G>C [p.(Ala159Pro)], found in 4 families, and
      c.1052G>A [p.(Arg351His)], found in 1 family, are most probably causative. They
      also show that WNT10B variants are associated not only with oligodontia and
      isolated tooth agenesis, but also with microdontia, short tooth roots, dental
      pulp stones, and taurodontism.

PMID- 29364502
TI  - ARRDC3 suppresses colorectal cancer progression through destabilizing the
      oncoprotein YAP.
AB  - Although colorectal cancer (CRC) is a prevalent malignancy of the digestive
      system, the underlying mechanisms of CRC tumorigenesis are still elusive.
      Arrestin-related domain-containing protein-3 (ARRDC3) has been reported to
      promote lysosome-mediated protein degradation. In the present study, we find that
      the expression of ARRDC3 is downregulated in CRC specimens. Mechanistically, we
      reveal that ARRDC3 binds and decreases expression of the oncoprotein YAP, the
      cotranscription factor of the Hippo pathway. The regulation of the Hippo pathway
      by ARRDC3 is conserved from Drosophila to mammals. Furthermore, we demonstrate
      that ARRDC3 plays an anti-oncogenic role in CRC progression by promoting YAP
      degradation. Finally, we show that ARRDC3 increases the sensitivity of CRC cells
      toward chemotherapeutic drugs. Taken together, our findings point to ARRDC3 as a
      potential target for CRC treatment.

PMID- 29364503
TI  - Surgery for postvitrectomy cataract.
AB  - BACKGROUND: Cataract formation or acceleration can occur after intraocular
      surgery, especially following vitrectomy, a surgical technique for removing the
      vitreous that is used in the treatment of many disorders that affect the
      posterior segment of the eye. The underlying problem that led to vitrectomy may
      limit the benefit from removal of the cataractous lens. OBJECTIVES: To evaluate
      the effectiveness and safety of surgery versus no surgery for postvitrectomy
      cataract with respect to visual acuity, quality of life, and other outcomes.
      SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017,
      Issue 5), MEDLINE Ovid (1946 to 17 May 2017), Embase.com (1947 to 17 May 2017),
      PubMed (1946 to 17 May 2017), Latin American and Caribbean Health Sciences
      Literature database (LILACS) (January 1982 to 17 May 2017), the metaRegister of
      Controlled Trials (mRCT) (www.controlled-trials.com); last searched May 2013,
      ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 May 2017, and the World
      Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en); searched 17 May 2017. We did not use any date or
      language restrictions in the electronic searches for trials. SELECTION CRITERIA:
      We planned to include randomized controlled trials (RCTs) and quasi-RCTs that had
      compared surgery versus no surgery to remove the lens from eyes of adults in
      which cataracts had developed following vitrectomy. DATA COLLECTION AND ANALYSIS:
      Two review authors independently screened the search results according to the
      standard methodological procedures expected by Cochrane. MAIN RESULTS: We found
      no RCTs or quasi-RCTs that had compared surgery versus no surgery to remove the
      lens from eyes of adults in which cataracts had developed following vitrectomy.
      AUTHORS' CONCLUSIONS: There is no evidence from RCTs or quasi-RCTs on which to
      base clinical recommendations for surgery for postvitrectomy cataract. There is a
      clear need for RCTs to address this evidence gap. Such trials should stratify
      participants by their age, the retinal disorder leading to vitrectomy, and the
      status of the underlying disease process in the contralateral eye. Outcomes
      assessed in such trials may include changes (both gains and losses) of visual
      acuity, quality of life, and adverse events such as posterior capsular rupture
      and retinal detachment. Both short-term (six-month) and long-term (one- or two
      year) outcomes should be examined.

PMID- 29364504
TI  - Rapid and sensitive surface-enhanced Raman spectroscopy (SERS) method combined
      with gold nanoparticles for determination of paraquat in apple juice.
AB  - BACKGROUND: Paraquat, a highly efficient herbicide, is widely used in
      agricultural practices throughout the world. However, paraquat residues in food
      pose a threat to human health. In order to develop a rapid and sensitive method,
      surface-enhanced Raman spectroscopy (SERS) coupled with gold nanoparticles was
      applied to analysis of paraquat in apple juice. RESULTS: Natural organic
      compounds (sugars and organic acids) in apple juice interfered with SERS
      measurement. Sample preparation was needed. Paraquat could be detected at
      concentrations as low as 0.02 and 0.1 ug mL- 1 with the weak cation-exchange
      solid-phase extraction (WCX-SPE) method and dilution method for sample
      preparation, respectively. For quantitative analysis, the R2 cv of the partial
      least-squares regression model with the dilution method (0.939) was not as good
      as with the WCX-SPE method (0.984), but the dilution method is much less costly,
      simpler and time saving. Satisfactory recovery values were obtained ranging from
      94.73% to 114.81%, with the exception of 56.55% for the lowest concentration.
      CONCLUSION: This work showed that SERS combined with gold nanoparticles could
      determine paraquat in apple juice. As a simple, rapid and ultrasensitive method,
      it has great practical potential for detection of other contaminants in a variety
      of foods. (c) 2018 Society of Chemical Industry.

PMID- 29364505
TI  - The application of digestive tract lactic acid bacteria with high esterase
      activity for zearalenone detoxification.
AB  - BACKGROUND: Zearalenone (ZEA) is an estrogenic mycotoxin produced by several
      Fusarium species and frequently contaminates cereals used for food or animal
      feed. This study attempted to select lactic acid bacteria (LAB) with high
      esterase activity from the digestive tract, with the goal of using these bacteria
      for ZEA detoxification. RESULTS: No ZEA activity-related biotransformation
      products were observed in three isolates (B1, B2 and D10) during incubation in
      the presence of ZEA. All three LAB strains were Lactobacillus plantarum, but the
      API 50 CHL results suggested that the three isolates were different strains.
      Increased esterase activity was associated with an increase in cell growth, and
      the ZEA-detoxifying capabilities of isolates rely on the concentration of
      bacteria in the culture medium. The lipolytic activity and ZEA removal assay
      indicated that ZEA degradation by the supernatant fraction was dependent on
      esterase activity; the supernatant of B2 strain showed the highest ZEA
      degradation ability and did not release the binding ZEA back into the medium. The
      D10 strain showed fast ZEA binding ability during the late log phase but began to
      release the bound ZEA back into the medium after the early stationary phase. All
      isolates showed good acid and bile salt tolerance ability but all strains showed
      low adhesion ability to epithelial cells. CONCLUSION: Based on the ZEA removal
      characterization and ability of the isolates, it is suggested that the isolates
      could be applied to ZEA detoxification of contaminated feed, but the with the
      requirement of high cell number for ZEA binding and limited degradation time
      before absorption of ZEA in the digestive tract. (c) 2018 Society of Chemical
      Industry.

PMID- 29364507
TI  - Decreased rates of cerebral protein synthesis measured in vivo in a mouse model
      of Tuberous Sclerosis Complex: unexpected consequences of reduced tuberin.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder
      affecting about 1 in 6000 people and is caused by mutations in either TSC1 or
      TSC2. This disorder is characterized by increased activity of mammalian target of
      rapamycin complex 1 (mTORC1), which is involved in regulating ribosomal
      biogenesis and translation initiation. We measured the effects of Tsc2
      haploinsufficiency (Tsc2+/- ) in 3-month-old male mice on regional rates of
      cerebral protein synthesis (rCPS) by means of the in vivo L-[1-14 C]leucine
      method. This quantitative autoradiographic method includes an estimate of the
      integrated specific activity of the tracer amino acid in brain tissue. The
      estimate accounts for recycling of unlabeled amino acids from tissue protein
      breakdown by means of a factor (lambda) that was determined in control and Tsc2+/
      mice. The value of lambda was higher in Tsc2+/- mice, indicating that a greater
      fraction of leucine in the tissue precursor pool for protein synthesis is derived
      from the plasma compared to controls, consistent with reduced rates of protein
      degradation. We determined rCPS in freely moving, awake male Tsc2+/- and control
      mice, and we used the determined values of lambda in the calculation of rCPS.
      Unexpectedly, we found that rCPS were significantly decreased in 16 of the 17
      brain regions analyzed in Tsc2+/- mice compared to controls. Our results indicate
      a complex role of mTORC1 in the regulation of cerebral protein synthesis that has
      not been previously recognized.

PMID- 29364508
TI  - Selection of Leuconostoc strains isolated from artisanal Serrano Catarinense
      cheese for use as adjuncts in cheese manufacture.
AB  - BACKGROUND: Serrano Catarinense cheese is a raw bovine milk cheese produced in
      the region of Santa Catarina, Brazil. Twelve representative strains of
      Leuconostoc isolated from 20 samples of this artisanal cheese were selected and
      submitted for evaluation of the acidifying, proteolytic, autolytic,
      aminopeptidase and lipolytic activities, NaCl and acid resistance, production of
      dextran and biogenic amines and antimicrobial activity. The aim was to
      genetically and technologically characterize the Leuconostoc strains in order to
      use them in mixed starter cultures for cheese manufacture. RESULTS: Leuconostoc
      mesenteroides subsp. mesenteroides was the species that accounted for the largest
      proportion of isolates of Leuconostoc genus. Two leuconostoc isolates stood out
      in the acidifying activity, with reduction in pH of 1.12 and 1.04 units. The
      isolates showed low proteolytic and autolytic activity. Most of the isolates were
      dextran producers, presented good resistance to the salt and pH conditions of the
      cheese and showed antimicrobial activity against cheese pathogen bacteria, and
      none of them produced biogenic amines. CONCLUSION: These results allowed the
      selection of five strains (UEL 04, UEL 12, UEL 18, UEL 21 and UEL 28) as good
      candidates for use as adjunct cultures for cheese manufacture. (c) 2018 Society
      of Chemical Industry.

PMID- 29364506
TI  - The mitochondrial transcription factor TFAM in neurodegeneration: emerging
      evidence and mechanisms.
AB  - The mitochondrial transcription factor A, or TFAM, is a mitochondrial DNA (mtDNA)
      binding protein essential for genome maintenance. TFAM functions in determining
      the abundance of the mitochondrial genome by regulating packaging, stability, and
      replication. More recently, TFAM has been shown to play a central role in the
      mtDNA stress-mediated inflammatory response. Emerging evidence indicates that
      decreased mtDNA copy number is associated with several aging-related pathologies;
      however, little is known about the association of TFAM abundance and disease. In
      this Review, we evaluate the potential associations of altered TFAM levels or
      mtDNA copy number with neurodegeneration. We also describe potential mechanisms
      by which mtDNA replication, transcription initiation, and TFAM-mediated
      endogenous danger signals may impact mitochondrial homeostasis in Alzheimer,
      Huntington, Parkinson, and other neurodegenerative diseases.

PMID- 29364509
TI  - Early psychotherapeutic empathy, alliance, and client outcome: Preliminary
      evidence of indirect effects.
AB  - The association between psychotherapeutic empathy and client outcome is well
      established, yet the mechanisms underlying this association remain poorly
      understood. We hypothesized that early experiences of empathy influence outcome
      through the working alliance. To test this hypothesis, we used archival data
      collected from 56 clients (mean [M] age = 19.5 years, 83.9% female, 76.8% White)
      who reported mild, moderate, or severe depressive symptoms at screening and
      pretreatment assessments and then received five sessions of evidence-based
      psychotherapy. Therapists (M age = 26.0 years, 50% female, 100% White) were six
      students in a clinical psychology PhD program. Results of bootstrap analyses were
      consistent with the idea that early experiences of empathy strengthen the
      alliance (specifically the goals and tasks facets), which in turn facilitates
      improvements in depressive symptoms and psychological well-being. While
      preliminary, these results implicate a specific pathway of change in the
      treatment of depression.

PMID- 29364510
TI  - Structural basis of the specific interactions of GRAS family proteins.
AB  - The plant-specific GAI-RGA-and-SCR (GRAS) family of proteins function as
      transcriptional regulators and play critical roles in development and signalling.
      Recent structural studies have shed light on the molecular functions at the
      structural level. The conserved GRAS domain comprises an alpha-helical cap and
      alpha/beta core subdomains. The alpha-helical cap mediates head-to-head
      heterodimerization between SHR and SCR GRAS domains. This type of dimerization is
      predicted for the NSP1-NSP2 heterodimer and DELLA proteins such as RGA and SLR1
      homodimers. The alpha/beta core subdomain possesses a hydrophobic groove formed
      by surface alpha3- and alpha7-helices and mediates protein-protein interactions.
      The groove of the SHR GRAS domain accommodates the zinc fingers of JKD, a
      BIRD/IDD family transcription factor, while the groove of the SCL7 GRAS domain
      mediates the SCL7 homodimerization.

PMID- 29364511
TI  - [18 F]GE180 positron emission tomographic imaging indicates a potential double
      hit insult in the intrahippocampal kainate mouse model of temporal lobe epilepsy.
AB  - OBJECTIVE: Accumulating evidence suggests that brain inflammation, elicited by
      epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear
      imaging of brain inflammation in animal models of epileptogenesis represents a
      diagnostic in vivo approach with potential for direct translation into the
      clinic. Here, we investigated up-regulation of the translocator protein (TSPO)
      indicative of microglial activation by serial [18 F]GE180 positron emission
      tomographic (PET) imaging in a mouse model of temporal lobe epilepsy. METHODS: As
      epileptogenic insult, a status epilepticus (SE) was induced in mice by
      intrahippocampal injection of kainate. Post-SE mice injected with kainate and
      sham-injected mice were subjected to [18 F]GE180 PET scans before SE and at 2
      days, 5-7 days, 2 weeks, 3 weeks, 7 weeks, and 14 weeks postinsult. For data
      evaluation, brain regions ipsilateral and contralateral to the injection site
      were outlined by coregistration with a standard mouse brain atlas, and percentage
      of injected dose per cubic centimeter was calculated. In addition, a statistical
      parametric mapping analysis, comparing post-SE mice to baseline, sham mice to
      baseline, and post-SE to sham mice was performed. RESULTS: Following SE,
      elevations in [18 F]GE180 uptake were most prominent in the ipsilateral
      hippocampus, occurring between 2 days and at least 7 weeks after SE, with a peak
      at 5-7 days after SE. In the contralateral hippocampus and other epilepsy
      associated brain regions, increased tracer uptake was observed with a similar
      time profile but to a lesser extent. Moderate enhancement of tracer uptake was
      also evident in mice after sham surgery. SIGNIFICANCE: TSPO in vivo imaging
      reliably detects brain inflammation during epileptogenesis. These inflammatory
      processes most prominently affect the hippocampus ipsilateral to the injection
      site. Inflammation induced by the traumatic insult associated with surgery
      synergistically contributes to total brain inflammation and may also contribute
      to epileptogenesis. The revealed time course of neuroinflammation will help to
      identify appropriate time points for anti-inflammatory, potentially
      antiepileptogenic treatment.

PMID- 29364512
TI  - The creation and integration of a nurse educator position in two hospitals in
      Haiti.
AB  - BACKGROUND: Continuing education is an integral part of nursing professional
      development and improving healthcare delivery, but literature on continuing
      education initiatives in low-resource settings is limited. PURPOSE: To describe
      the creation and integration of a nurse educator (NE) position in two Haitian
      hospitals and highlight barriers and facilitators experienced by the NEs in their
      role. METHODS: Four NEs and three support staff involved in the creation and
      integration of the NE positions were interviewed. Supplementary data were
      gathered through participant observation and document review. Data were compiled
      and summarized. DISCUSSION: NEs were hired to assess learning needs, evaluate
      skills, train and mentor nurses, and provide ongoing support to assure
      application of new knowledge. Barriers included lack of specialized training and
      limited informational resources to develop education activities, role confusion
      and heavy workload, poor attendance and disparate education needs of nurses, and
      insufficient hospital resources and support to implement practice changes.
      Facilitators included previous management experience, peer support, and a
      perception of being valued by patients and colleagues and making a difference
      regarding nursing care and patient outcomes. CONCLUSION: The NE is a leadership
      role and a promising, sustainable initiative for developing the nursing
      profession in Haiti.

PMID- 29364513
TI  - N-Palmitoyl Ethanol Amide Pharmacological Treatment in Patients With Nonsurgical
      Lumbar Radiculopathy.
AB  - Palmitoyl ethanol amide (PEA) is an endogenous substance that plays a role in
      neuropathic pain. In this article, we evaluated both the safety and the efficacy
      of ultramicronized PEA (um-PEA) in the treatment of low back pain related to
      nonsurgical lumbar radiculopathy. In this prospective single-blind study,
      patients with low back pain related to nonsurgical lumbar radiculopathy received
      the fixed combination acetaminophen/codeine (500 mg + 30 mg/d) for 7 days, and
      then it was stopped and changed to um-PEA (1200 mg/d) for 30 days. Patients
      without an improvement in pain or disability started a second cycle of treatment
      with um-PEA (600 mg/d in tablets) for 30 days and then acetaminophen/codeine for
      30 days. A total of 155 patients were included in the analysis. After the first
      cycle of treatment we recorded an improvement of pain in all patients with mild
      pain (visual analog scale score from 3-4 to 1) and in 75% of the patients with
      moderate pain (visual analog scale score from 5-6 to 2). After the second cycle,
      we recorded an improvement of pain and disability in all patients with moderate
      pain (P < .01), but in 26% of patients with severe pain we did not record any
      improvement in disability (P > .05). In conclusion we evaluated the role of um
      PEA in patients with lumbar radiculopathy with a long-term follow-up (24 months)
      and put in evidence the effectiveness and the safety of this formulation in
      patients with mild and moderate pain.

PMID- 29364514
TI  - E3 ubiquitin ligases Cbl-b and c-Cbl downregulate PD-L1 in EGFR wild-type non
      small cell lung cancer.
AB  - Anti-PD-1/PD-L1 therapies have demonstrated prominent clinical effects in the
      treatment of non-small cell lung cancer (NSCLC). However, limited understanding
      of the regulatory mechanisms of PD-L1 has become one of the biggest challenges
      for further improving efficacy. In this study, we observed that in wild-type EFGR
      cell lines A549 and H460, the ubiquitin ligases Cbl-b and c-Cbl inhibit PD-L1 by
      inactivating STAT, AKT, and ERK signaling. MiR-181a and miR-940 were screened and
      validated to target Cbl-b and c-Cbl, respectively. Furthermore, in NSCLC tissues,
      the expression of Cbl-b/c-Cbl is negatively correlated with PD-L1 expression.
      Taken together, these findings indicated a new regulatory mechanism for PD-L1 in
      wild-type EGFR NSCLC cell lines by Cbl-b and c-Cbl.

PMID- 29364515
TI  - A Canadian upland forest soil profile and carbon stocks database.
AB  - "A Canadian upland forest soil profile and carbon stocks database" was compiled
      in phases over a period of 10 years to address various questions related to
      modeling upland forest soil carbon in a national forest carbon accounting model.
      For 3,253 pedons, the SITES table contains estimates for soil organic carbon
      stocks (Mg/ha) in organic horizons and mineral horizons to a 100-cm depth, soil
      taxonomy, leading tree species, mean annual temperature, annual precipitation,
      province or territory, terrestrial ecozone, and latitude and longitude, with an
      assessment of the quality of information about location. The PROFILES table
      contains profile data (16,167 records by horizon) used to estimate the carbon
      stocks that appear in the SITES table, plus additional soil chemical and physical
      data, where provided by the data source. The exceptions to this are estimates for
      soil carbon stocks based on Canadian National Forest Inventory data (NFI [2006]
      in REFERENCES table), where data were collected by depth increment rather than
      horizon and, therefore, total soil carbon stocks were calculated separately
      before being entered into the SITES table. Data in the PROFILES table include the
      carbon stock estimate for each horizon (corrected for coarse fragment content),
      and the data used to calculate the carbon stock estimate, such as horizon
      thickness, bulk density, and percent organic carbon. The PROFILES table also
      contains data, when reported by the source, for percent carbonate carbon, pH,
      percent total nitrogen, particle size distribution (percent sand, silt, clay),
      texture class, exchangeable cations, cation and total exchange capacity, and
      percent Fe and Al. An additional table provides references (REFERENCES table) for
      the source data. Earlier versions of the database were used to develop national
      soil carbon modeling categories based on differences in carbon stocks linked to
      soil taxonomy and to examine the potential of using soil taxonomy and leading
      tree species to improve accuracy in modeled predictions. The current database is
      being used to develop soil carbon model parameters linked to soil taxonomy and
      leading tree species and, by various governmental and nongovernmental
      organizations, to improve digital mapping of ecosite types and soil properties
      regionally, nationally, and internationally. (c) Her Majesty the Queen in Right
      of Canada, 2018. Information contained in this publication or product may be
      reproduced, in part or in whole, and by any means, for personal or public non
      commercial purposes, without charge or further permission, unless otherwise
      specified. You are asked to: exercise due diligence in ensuring the accuracy of
      the materials reproduced; indicate the complete title of the materials
      reproduced, and the name of the author organization; indicate that the
      reproduction is a copy of an official work that is published by Natural Resources
      Canada (NRCan) and that the reproduction has not been produced in affiliation
      with, or with the endorsement of, NRCan. Commercial reproduction and distribution
      is prohibited except with written permission from NRCan. For more information,
      contact NRCan at copyright.droitdauteur@nrcan-rncan.gc.ca.

PMID- 29364516
TI  - Iron promotes alpha-synuclein aggregation and transmission by inhibiting TFEB
      mediated autophagosome-lysosome fusion.
AB  - Recent studies have strongly shown that cell-to-cell transmission of
      neuropathogenic proteins is a common mechanism for the development of
      neurodegenerative diseases. However, the underlying cause is complex and little
      is known. Although distinct processes are involved in the pathogenesis of various
      diseases, they all share the common feature of iron accumulation, an attribute
      that is particularly prominent in synucleinopathies. However, whether iron is a
      cofactor in facilitating the spread of alpha-synuclein remains unclear. Here, we
      constructed a cell-to-cell transmission model of alpha-synuclein using SN4741
      cell line based on adenovirus vectors. Cells were treated with FeCl2, and alpha
      synuclein aggregation and transmission were then evaluated. In addition, the
      possible mechanisms were investigated through gene knockdown or over-expression.
      Our results demonstrated that iron promoted alpha-synuclein aggregation and
      transmission by inhibiting autophagosome-lysosome fusion. Furthermore, iron
      decreased the expression of nuclear transcription factor EB (TFEB), a master
      transcriptional regulator of autophagosome-lysosome fusion, and inhibited its
      nuclear translocation through activating AKT/mTORC1 signaling. After silencing
      TFEB, ratios of alpha-synuclein aggregation and transmission were not
      significantly altered by the presence of iron; on the other hand, when TFEB was
      over-expressed, the transmission of alpha-synuclein induced by iron was obviously
      reversed; suggesting the mechanism by which iron promotes alpha-synuclein
      transmission may be mediated by TFEB. Taken together, our data reveal a
      previously unknown relationship between iron and alpha-synuclein, and identify
      TFEB as not only a potential target for preventing alpha-synuclein transmission,
      but also a critical factor for iron-induced alpha-synuclein aggregation and
      transmission. Indeed, this newly discovered role of iron and TFEB in
      synucleinopathies may provide novel targets for developing therapeutic strategies
      to prevent alpha-synuclein transmission in Parkinson's disease.

PMID- 29364518
TI  - Protective Effect of Denosumab on Bone in Older Women with Primary
      Hyperparathyroidism.
AB  - OBJECTIVES: To determine the effect of denosumab, which is used in primary
      osteoporosis (PO), in primary hyperparathyroidism (PHPT)-related osteoporosis.
      DESIGN: Retrospective, longitudinal study. SETTING: Outpatient osteoporosis
      clinic. PARTICIPANTS: Older women with PHPT (78.6 +/- 5.5) (n = 25) and PO (78.8
      +/- 5.2) (n = 25) matched on age, body mass index, familial history of hip
      fracture, femoral bone mineral density (BMD), and personal history of fragility
      fractures. INTERVENTION: Twenty-four months of denosumab therapy. MEASUREMENTS:
      We assessed the calcium-phosphorus metabolism parameters; BMD at the lumbar spine
      (LS), femoral neck (FN), and total hip (TH) using dual X-ray absorptiometry; and
      morphometric vertebral fractures using radiographs in all subjects at baseline
      and after 24 months. Changes in BMD and total alkaline phosphatase (ALP) activity
      were considered significant if they were greater than the least significant
      change (LS 2.8%, FN 5.9%, TH 4.8%, ALP -22%) and were expressed as percentage
      difference between end of follow-up and baseline (Delta). RESULTS: After 24
      months, women with PHPT had greater DeltaALP (-30.6 +/- 11.3), DeltaFN (5.6 +/-
      4.8), and DeltaTH (4.8 +/- 4.4) than those with PO (DeltaALP -21.4 +/- 13.1,
      DeltaFN 2.9 +/- 4.8, DeltaTH 1.2 +/- 4.1, P < .05 for all comparisons). A
      significant increase in BMD was more frequent in women with PHPT (92%) than in
      those with PO (52%, P < .05) and it was 13.4 times as likely in women with PHPT
      as in those with PO (P = .02), regardless of possible confounders. Two subjects
      in each group had an incident fracture. CONCLUSIONS: Denosumab therapy is
      effective in older women with PHPT-related osteoporosis.

PMID- 29364517
TI  - Coffee, tea and caffeine consumption and risk of primary infertility in women: a
      Danish cohort study.
AB  - INTRODUCTION: The aim of this study was to investigate whether consumption of
      coffee, tea and caffeine affects the risk of primary infertility in women.
      MATERIAL AND METHODS: We selected nulliparous Danish women aged 20-29 years from
      a prospective cohort and retrieved information on coffee and tea consumption from
      a questionnaire and an interview at enrollment. We assessed the women's fertility
      by linkage to the Danish Infertility Cohort and retrieved information on children
      and vital status from the Civil Registration System. All 7574 women included for
      analysis were followed for primary infertility from the date of enrollment (1991
      1993) until 31 December 2010. Analyses were performed with Cox proportional
      hazard models. RESULTS: During follow up, primary infertility was diagnosed in
      822 women. Compared with never consumers, the risk of primary infertility among
      women who drank coffee or tea was not affected. The risk of primary infertility
      was neither associated with an increasing number of daily servings of coffee
      (hazard ratio 1.00; 95% confidence interval (CI), 0.97-1.03) or tea (hazard ratio
      1.01; 95% CI, 0.99-1.03) in consumers only. Concerning total caffeine consumption
      (from coffee and tea), the risk of infertility was similar among consumers
      compared with never consumers. Finally, none of the additional daily 100 mg of
      caffeine affected the risk among consumers only (hazard ratio 1.00; 95% CI 0.98
      1.02). CONCLUSIONS: In this population-based cohort study, not restricted to
      women seeking pregnancy, we found no association between coffee, tea or total
      caffeine consumption and the risk of primary infertility in women.

PMID- 29364519
TI  - CRISPR/Cas9-Mediated Fluorescent Tagging of Endogenous Proteins in Human
      Pluripotent Stem Cells.
AB  - Human induced pluripotent stem cells (hiPSCs) can be used to mass produce
      surrogates of human tissues, enabling new advances in drug screening, disease
      modeling, and cell therapy. Recent developments in clustered regularly
      interspaced short palindromic repeats (CRISPR)/Cas9 genome editing technology use
      homology-directed repair (HDR) to efficiently generate custom hiPSC lines
      harboring a variety of genomic insertions and deletions. Thus, hiPSCs that encode
      an endogenous protein fused to a fluorescent reporter protein can be rapidly
      created by employing CRISPR/Cas9 genome editing, enhancing HDR efficiency and
      optimizing homology arm length. These fluorescently tagged hiPSCs can be used to
      visualize protein function and dynamics in real time as cells proliferate and
      differentiate. Given that nearly any intracellular protein can be fluorescently
      tagged, this system serves as a powerful tool to facilitate new discoveries
      across many biological disciplines. In this unit, we present protocols for the
      design, generation, and monoclonal expansion of genetically customized hiPSCs
      encoding fluorescently tagged endogenous proteins. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 29364521
TI  - Biosafety in Handling Gene Transfer Vectors.
AB  - This unit is devoted to safety issues that must be considered when generating and
      working with the most common vectors under development for human gene therapy
      today. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29364520
TI  - Balanced Chromosomal Rearrangement Detection by Low-Pass Whole-Genome Sequencing.
AB  - Balanced chromosomal rearrangements (or balanced chromosome abnormalities, BCAs)
      are common chromosomal structural variants. Emerging studies have demonstrated
      the feasibility of using whole-genome sequencing (WGS) for detection of BCA
      associated breakpoints, but the requirement for a priori knowledge of the
      rearranged regions from G-banded chromosome analysis limits its application. The
      protocols described here are based on low-pass WGS for detecting BCA events
      independent from chromosome analysis, and has been validated using genomic data
      from the 1000 Genomes Project. This approach adopts non-size-selected mate-pair
      library (3~8 kb) with 2~3 MUg DNA as input, and requires only 30 million read
      pairs (50 bp, equivalent to 1-fold base-coverage) for each sample. The complete
      procedure takes 13 days and the total cost is estimated to be less than $600
      (USD) per sample. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29364522
TI  - Differentiation and Contractile Analysis of GFP-Sarcomere Reporter hiPSC
      Cardiomyocytes.
AB  - Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) represent
      a powerful cellular platform for illuminating mechanisms of human cardiovascular
      disease and for pharmacological screening. Recent advances in CRISPR/Cas9
      mediated genome editing technology underlie this profound utility. We have
      generated hiPSC-CMs harboring fluorescently-tagged sarcomeric proteins, which
      provide a tool to non-invasively study human sarcomere function and dysfunction.
      In this unit, we illustrate methods for conducting high-efficiency, small
      molecule-mediated differentiation of hiPSCs into cardiomyocytes, and for
      performing non-invasive contractile analysis through direct sarcomere tracking of
      GFP-sarcomere reporter hiPSC-CMs. We believe that this type of analysis can
      overcome sensitivity problems found in other forms of contractile assays
      involving hiPSC-CMs by directly measuring contractility at the fundamental
      contractile unit of the hiPSC-CM, the sarcomere. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 29364523
TI  - Population Pharmacokinetics of the TNF-alpha and IL-17A Dual-Variable Domain
      Antibody ABT-122 in Healthy Volunteers and Subjects With Psoriatic or Rheumatoid
      Arthritis: Analysis of Phase 1 and 2 Clinical Trials.
AB  - ABT-122 is an IgG1 dual-variable domain immunoglobulin that specifically blocks
      TNF-alpha and IL-17A. This work characterized ABT-122 pharmacokinetics using
      nonlinear mixed-effects modeling and ABT-122 serum concentrations from 72 healthy
      subjects, 196 subjects with rheumatoid arthritis (RA), and 144 subjects with
      psoriatic arthritis (PsA) enrolled in 4 phase 1 and 2 phase 2 studies (0.1-10
      mg/kg intravenously and 0.3-3 mg/kg subcutaneous single doses and 0.3-3.0 mg/kg
      subcutaneous and 60-240 mg subcutaneous doses weekly or every other week). A 2
      compartment model with a combination of linear clearance (0.419 L/day) and
      nonlinear clearance (relevant only at low doses; Vmax and Km of 0.155 mg/day and
      0.0458 mg/L, respectively) described ABT-122 pharmacokinetics. Subcutaneous
      bioavailability was 35%-58% across formulations and populations. Body weight was
      a significant covariate for ABT-122 clearance, with subjects with body weight of
      140 and 40 kg estimated to have 38% lower and 43% higher ABT-122 AUC,
      respectively, compared with a 70-kg reference subject. ABT-122 antidrug antibody
      (ADA) titer (ADA incidence, 47%; 0 to 519 000 titer range in the data set) was a
      continuous covariate on ABT-122 clearance. An ADA titer of 100 units resulted in
      a 5-fold increase in clearance. Sex, age, and baseline serum albumin or baseline
      C-reactive protein level did not impact ABT-122 exposure. Fixed-effects and
      random-effects parameters were estimated with a relative standard error of <=17%
      and <=28%, respectively, and the model was qualified using bootstrap analysis and
      visual predictive checks. This analysis characterized ABT-122 exposure across
      populations and supported exposure-response analyses of ABT-122 efficacy in RA
      and PsA.

PMID- 29364524
TI  - OsMADS57 together with OsTB1 coordinates transcription of its target OsWRKY94 and
      D14 to switch its organogenesis to defense for cold adaptation in rice.
AB  - Plants modify their development to adapt to their environment, protecting
      themselves from detrimental conditions such as chilling stress by triggering a
      variety of signaling pathways; however, little is known about how plants
      coordinate developmental patterns and stress responses at the molecular level.
      Here, we demonstrate that interacting transcription factors OsMADS57 and OsTB1
      directly target the defense gene OsWRKY94 and the organogenesis gene D14 to trade
      off the functions controlling/moderating rice tolerance to cold. Overexpression
      of OsMADS57 maintains rice tiller growth under chilling stress. OsMADS57 binds
      directly to the promoter of OsWRKY94, activating its transcription for the cold
      stress response, while suppressing its activity under normal temperatures. In
      addition, OsWRKY94 was directly targeted and suppressed by OsTB1 under both
      normal and chilling temperatures. However, D14 transcription was directly
      promoted by OsMADS57 for suppressing tillering under the chilling treatment,
      whereas D14 was repressed for enhancing tillering under normal condition.We
      demonstrated that OsMADS57 and OsTB1 conversely affect rice chilling tolerance
      via targeting OsWRKY94. Our findings highlight a molecular genetic mechanism
      coordinating organogenesis and chilling tolerance in rice, which supports and
      extends recent work suggesting that chilling stress environments influence organ
      differentiation.

PMID- 29364525
TI  - Intestinal parasites: Associations with intestinal and systemic inflammation.
AB  - The aim of the present study was to evaluate associations between intestinal
      parasitic infection with intestinal and systemic inflammatory markers in school
      aged children with high rates of obesity. Plasma concentrations of C-Reactive
      Protein (CRP), leptin, TNF-alpha, IL-6 and IL-10 were measured as systemic
      inflammation markers and count of stool leukocytes as marker of intestinal
      inflammation in 291 children (6-10 years). Intestinal parasitic infection was
      measured by stool examination. Logistic regression analyses were performed to
      determine the odds of having high inflammatory markers for each parasite or group
      of parasites as compared to parasite-free children while adjusting for sex, age,
      mother's educational level and percentage of body fat. The prevalence of soil
      transmitted helminths and intestinal protozoa infections was 12% and 36%,
      respectively. Parasitic infection was not associated with CRP, IL-6, IL-10 or TNF
      alpha. Children infected with Ascaris lumbricoides (aOR: 5.91, 95% CI: 1.97
      17.70) and Entamoeba coli (aOR: 8.46, 95% CI: 2.85-25.14) were more likely to
      have higher stool leucocytes than parasite-free children. Children with multiple
      infections (aOR: 10.60, 95% CI: 2.85-25.14) were more likely to have higher
      leptin concentrations than parasite-free children. Intestinal parasitic infection
      was not associated with systemic inflammation, but was associated with intestinal
      inflammation. Having multiple infections were associated with higher leptin
      concentrations.

PMID- 29364526
TI  - Practice environment as perceived by nurses in acute care hospitals in Sharjah
      and North Emirates.
AB  - AIM: To explore nurses' perceptions of their practice environment in acute care
      hospitals in Sharjah and North Emirates in the United Arab Emirates (UAE).
      BACKGROUND: The health of the environment in which registered nurses' work is
      critical to nursing outcomes. The interest to examine the practice environment
      extended to the Gulf area which has a complex healthcare system including the
      UAE. METHODS: The study used an exploratory descriptive design with a qualitative
      part using two focus group interviews. The sample size was 450 nurses selected
      through a random sampling method. A self-administered questionnaire including the
      Practice Environment Scale of Nursing Work Index (PES-NWI) was used. In addition,
      semi-structured interviews for two focus groups were done. RESULTS: The results
      showed that UAE practicing nurses reported favorable perceptions of most aspects
      of their practice environment. Unfavorable perceptions were only reported for
      Staffing and Resource Adequacy. The analysis of focus group discussions resulted
      in different emerged themes such as Lack of Recognition and Career Promotion, and
      Nurses' Workload due to Paper and Administrative Work. CONCLUSIONS: The findings
      of this study suggest that strategic interventions are needed to secure adequate
      staff and resources and implement an effective system for evaluation of
      performance.

PMID- 29364527
TI  - The process of reflection: A principle-based concept analysis.
AB  - The purpose of this paper is to evaluate the concept reflection as a process
      using a principle-based method of analysis that acknowledges the philosophical
      premises of formal cognitive operations (experiencing, understanding, judging,
      and deciding) espoused by Bernard Lonergan. The aim is to understand how we think
      and process cognitively in reflection while developing consciousness in knowing.
      Using Lonergan's formal cognitive operations adds a philosophical perspective and
      structure to the concept. Fostering the enactment of reflection is a complex
      process, but it is vital for nursing science and disciplinary advancement.

PMID- 29364528
TI  - Phylogenetic, expression and functional characterizations of the maize NLP
      transcription factor family reveal a role in nitrate assimilation and signaling.
AB  - Although nitrate represents an important nitrogen (N) source for maize, a major
      crop of dryland areas, the molecular mechanisms of nitrate uptake and
      assimilation remain poorly understood. Here, we identified nine maize NIN-like
      protein (ZmNLP) genes and analyzed the function of one member, ZmNLP3.1, in
      nitrate nutrition and signaling. The NLP family genes were clustered into three
      clades in a phylogenic tree. Comparative genomic analysis showed that most ZmNLP
      genes had collinear relationships to the corresponding NLPs in rice, and that the
      expansion of the ZmNLP family resulted from segmental duplications in the maize
      genome. Quantitative PCR analysis revealed the expression of ZmNLP2.1, ZmNLP2.2,
      ZmNLP3.1, ZmNLP3.2, ZmNLP3.3, and ZmNLP3.4 was induced by nitrate in maize roots.
      The function of ZmNLP3.1 was investigated by overexpressing it in the Arabidopsis
      nlp7-1 mutant, which is defective in the AtNLP7 gene for nitrate signaling and
      assimilation. Ectopic expression of ZmNLP3.1 restored the N-deficient phenotypes
      of nlp7-1 under nitrate-replete conditions in terms of shoot biomass, root
      morphology and nitrate assimilation. Furthermore, the nitrate induction of
      NRT2.1, NIA1, and NiR1 gene expression was recovered in the 35S::ZmNLP3.1/nlp7-1
      transgenic lines, indicating that ZmNLP3.1 plays essential roles in nitrate
      signaling. Taken together, these results suggest that ZmNLP3.1 plays an essential
      role in regulating nitrate signaling and assimilation processes, and represents a
      valuable candidate for developing transgenic maize cultivars with high N-use
      efficiency.

PMID- 29364529
TI  - Time separation technique: Accurate solution for 4D C-Arm-CT perfusion imaging
      using a temporal decomposition model.
AB  - PURPOSE: The issue of perfusion imaging using a temporal decomposition model is
      to enable the reconstruction of undersampled measurements acquired with a slowly
      rotating x-ray-based imaging system, for example, a C-arm-based cone beam
      computed tomography (CB-CT). The aim of this work is to integrate prior knowledge
      into the dynamic CT task in order to reduce the required number of views and the
      computational effort as well as to save dose. The prior knowledge comprises of a
      mathematical model and clinical perfusion data. METHODS: In case of model-based
      perfusion imaging via superposition of specified orthogonal temporal basis
      functions, a priori knowledge is incorporated into the reconstructions. Instead
      of estimating the dynamic attenuation of each voxel by a weighting sum, the
      modeling approach is done as a preprocessing step in the projection space. This
      point of view provides a method that decomposes the temporal and spatial domain
      of dynamic CT data. The resulting projection set consists of spatial information
      that can be treated as individual static CT tasks. Consequently, the high
      dimensional model-based CT system can be completely transformed, allowing for the
      use of an arbitrary reconstruction algorithm. RESULTS: For CT, reconstructions of
      preprocessed dynamic in silico data are illustrated and evaluated by means of
      conventional clinical parameters for stroke diagnostics. The time separation
      technique presented here, provides the expected accuracy of model-based CT
      perfusion imaging. Consequently, the model-based handled 4D task can be solved
      approximately as fast as the corresponding static 3D task. CONCLUSION: For C-arm
      based CB-CT, the algorithm presented here provides a solution for resorting to
      model-based perfusion reconstruction without its connected high computational
      cost. Thus, this algorithm is potentially able to have recourse to the benefit
      from model-based perfusion imaging for practical application. This study is a
      proof of concept.

PMID- 29364530
TI  - Cancer genetics meets biomolecular mechanism-bridging an age-old gulf.
AB  - Increasingly available genomic sequencing data are exploited to identify genes
      and variants contributing to diseases, particularly cancer. Traditionally,
      methods to find such variants have relied heavily on allele frequency and/or
      familial history, often neglecting to consider any mechanistic understanding of
      their functional consequences. Thus, while the set of known cancer-related genes
      has increased, for many, their mechanistic role in the disease is not completely
      understood. This issue highlights a wide gap between the disciplines of genetics,
      which largely aims to correlate genetic events with phenotype, and molecular
      biology, which ultimately aims at a mechanistic understanding of biological
      processes. Fortunately, new methods and several systematic studies have proved
      illuminating for many disease genes and variants by integrating sequencing with
      mechanistic data, including biomolecular structures and interactions. These have
      provided new interpretations for known mutations and suggested new disease
      relevant variants and genes. Here, we review these approaches and discuss
      particular examples where these have had a profound impact on the understanding
      of human cancers.

PMID- 29364531
TI  - Maturation periods for Coffea arabica cultivars and their implications for yield
      and quality in Brazil.
AB  - BACKGROUND: Climatic conditions directly affect the maturation period of coffee
      plantations, affecting yield and beverage quality. The quality of coffee
      beverages is highly correlated with the length of fruit maturation, which is
      strongly influenced by meteorological elements. The objective was to estimate the
      probable times of graining and maturation of the main coffee varieties in Brazil
      and to quantify the influences of climate on coffee maturation. We used degree
      days to estimate flowering/graining periods (green fruit) and
      flowering/maturation periods (cherry fruit) for all cultivars. We evaluated the
      influence of climate on the time of maturity using Pearson correlation and
      nonlinear regression analysis and successfully mapped the influences of these
      elements. RESULTS: Arabica coffee matured up to 2-3 months earlier in Sao Paulo,
      where air temperatures (TAIR ) were higher, than in Minas Gerais, which would
      allow earlier harvesting and the training of seedlings at the beginning of the
      rainy season. Catuai-Amarelo-IAC-62 cultivar needed 205-226 days between the end
      of flowering and maturation at locations with high TAIR and 375-396 days at
      locations with low TAIR . CONCLUSION: Water surplus and deficit were generally
      the most important variables for coffee maturation. Coffee matured faster in
      regions with high TAIR and evapotranspiration, moderate altitudes and deficits.
      Acaia-Cerrado-MG-1474 and Icatu-Precoce-Amarelo-3282 were cultivars with an early
      cycle. (c) 2018 Society of Chemical Industry.

PMID- 29364532
TI  - Plant 'muscles': fibers with a tertiary cell wall.
AB  - Plants, although sessile organisms, are nonetheless able to move their body
      parts; for example, during root contraction of geophytes or in the gravitropic
      reaction by woody stems. One of the major mechanisms enabling these movements is
      the development of specialized structures that possess contractile properties.
      Quite unlike animal muscles, for which the action is driven by protein-protein
      interactions in the protoplasma, the action of plant 'muscles' is polysaccharide
      based and located in the uniquely designed, highly cellulosic cell wall that is
      deposited specifically in fibers. This review describes the development of such
      cell walls as a widespread phenomenon in the plant kingdom, gives reasons why it
      should be considered as a tertiary cell wall, and discusses the mechanism of
      action of the 'muscles'. The origin of the contractile properties lies in the
      tension of the axially oriented cellulose microfibrils due to entrapment of
      rhamnogalacturonan-I aggregates that limits the lateral interaction of
      microfibrils. Long side chains of the nascent rhamnogalacturonan-I are trimmed
      off during cell wall maturation leading to tension development. Similarities in
      the tertiary cell wall design in fibers of different plant origin indicate that
      the basic principles of tension creation may be universal in various
      ecophysiological situations.

PMID- 29364533
TI  - An interprofessional approach: The new paradigm in nursing education.

PMID- 29364534
TI  - Italian multicentre study found infectious and vaccine-preventable diseases in
      children adopted from Africa and recommends prompt medical screening.
AB  - AIM: This study evaluated the prevalence of infectious diseases and immunisation
      status of children adopted from Africa. METHODS: We studied 762 African children
      referred to 11 Italian paediatric centres in 2009-2015. Clinical and laboratory
      data were retrospectively collected and analysed. RESULTS: The median age of the
      children (60.3% males) was 3 years and 6 months, 52.6% came from Ethiopia and
      50.1% had at least one infectious disease. Parasitic infections accounted for the
      majority of the infectious diseases (409 of 715), and the most common were
      Giardia lamblia (n = 239), Toxocara canis (n = 65) and skin infections (n = 205),
      notably Tinea capitis/corporis (n = 134) and Molluscum contagiosum (n = 56)
      Active tuberculosis (TB) was diagnosed in nine children (1.2%). Latent TB
      infections were diagnosed in 52 (6.8%) children, and only 23 had concordant
      positive tuberculin skin tests and Quantiferon Gold In-Tube results. Discordant
      results were associated with Bacille de Calmette-Guerin vaccinations (odd ratio
      6.30 and 95% confidence interval of 1.01-39.20, p = 0.011). Nonprotective
      antitetanus or antihepatitis B antibody titres were documented in 266 (34.9%) and
      396 (51.9%) of the 762 children. CONCLUSION: The prevalence of infectious
      conditions and not-protective titres for vaccine-preventable diseases observed in
      our population underlines the need for prompt and complete medical screening of
      children adopted from Africa.

PMID- 29364535
TI  - Potential impacts of poor communication on early diagnosis of HIV-associated
      neurocognitive disorder.
AB  - AIM: To ascertain whether community-based healthcare providers were collecting
      appropriate information to identify patients at risk of HIV-associated
      neurocognitive disorder and whether related documentation was complete.
      BACKGROUND: HIV-associated neurocognitive disorder is a treatable neurological
      condition that can affect more than 20% of those infected with the HIV. Signs and
      symptoms of cognitive impairment may be subtle; therefore, documentation of
      medical and social information could be beneficial in identifying those at risk.
      DESIGN: Cross-sectional descriptive study. METHODS: An audit of patient records
      was completed by two community-based interdisciplinary teams with particular
      attention to the documentation of clinical and social indicators for those at
      risk of HIV-associated neurocognitive disorder. Data were collected over weeks
      during 2015. RESULTS: Data were retrieved from both electronic medical record
      systems and hard copy patient records. Documentation was incomplete in every
      patient record (N = 262), including the absence of important clinical data
      relating to nadir CD4 + T-cell count (91%), HIV viral load (36%), current
      caregiver (19%), and living circumstances (14%). Up to 40% of recorded
      medications and results were unconfirmed by the person's medical practitioner.
      CONCLUSION: Poor documentation can lead to incomplete information, which can
      delay early intervention for those at risk of HIV-associated neurocognitive
      disorder. Collection and recording of patient data needs to be consistent, as
      complete documentation is essential for integrating care, provision of clinical
      support and, importantly, for identifying those at risk of developing HIV
      associated neurocognitive disorder.

PMID- 29364536
TI  - Suicide by charcoal burning: a digital age phenomenon.

PMID- 29364537
TI  - High-fibre enteral feeding results in improved anthropometrics and favourable
      gastrointestinal tolerance in malnourished children with growth failure.
AB  - AIM: The practical value of using fibre-enriched enteral feeding regimens to
      rehabilitate malnourished children remains inconclusive. This study determined
      the usage patterns, gastrointestinal tolerance, anthropometrics and safety of
      high-fibre enteral feeding in malnourished children with growth failure. METHODS:
      This Turkish observational study between February 2013 and June 2015 comprised
      345 paediatric patients from 17 centres with malnutrition-related growth failure,
      with a weight and height of <2 SD percentiles for their age. Changes in
      anthropometrics, gastrointestinal symptoms, defecation habits and safety data
      relating to adverse events were analysed during the six-month follow-up period.
      RESULTS: Most subjects (99.7%) were supplemented with enteral feeding. The
      absolute difference and 95% confidence interval values for the Z scores of height
      for age, weight for age, weight for height and body mass index for height
      increased significantly in four months to six months to 0.21 (0.09-0.32), 0.61
      (0.51-0.70), 0.81 (0.56-1.06) and 0.70 (0.53-0.86), respectively (p < 0.001 for
      each). The percentage of patients with normal defecation frequency significantly
      increased from 70.3% to 92.8% at the four months to six months visit (p = 0.004).
      Adverse events occurred in 15 (4.3%) of patients. CONCLUSION: Using a six-month
      high-fibre enteral feeding was associated with favourable outcomes in
      anthropometrics, appetite, gastrointestinal tolerance and safety in malnourished
      children.

PMID- 29364538
TI  - Clonidine as a preoperative sedative.
AB  - The purpose of this study was to -examine the use of oral clonidine as a
      preoperative sedative prior to parenteral moderate sedation. Initially, four
      patients were given 0.2 mg oral clonidine but reduced to 0.1 mg clonidine due to 
      significant drops in blood pressure. Oral clonidine doses of 0.1 mg were then
      given to 19 patients preoperatively. In all these patients, blood pressure
      measurements decreased, but there were no significant differences in amounts of
      sedative agents needed in the clonidine group and the control group (N = 80). The
      conclusions reached suggest that clonidine has an advantage over other
      preoperative sedation agents in anxious patients exhibiting hypertension and
      tachycardia. However, the preop ideal dose required to reduce the amount of
      sedative drugs used as well as provide anxiolysis remains unknown. In further
      studies, different doses should be explored to determine what dosage of clonidine
      may offer hemodynamic protection as well as decrease sedative drugs needed.

PMID- 29364539
TI  - Hematological and Biochemical Assessment of Two Species of Freshwater Mussels,
      Quadrula quadrula and Amblema plicata, Following Translocation.
AB  - Nondestructive, sublethal, and sensitive health monitoring tools are needed to
      assess the health of freshwater mussels (family Unionidae). Recent developments
      to standardize hemocyte characterization have assisted in the hematologic
      assessment of wild and captive freshwater mussels. In this study, preliminary
      baseline hematological reference ranges were established for wild mapleleaf
      mussels Quadrula quadrula (n = 14) and threeridge mussels Amblema plicata (n =
      20) collected from the Muskingum River in Devola, Ohio. Mussels were collected
      from the wild, and hemolymph was sampled from each mussel in the field upon
      capture (baseline sample). They were then transported live to a propagation
      facility. Subsequent hemolymph samples were collected at 2 and 4 weeks and
      quarterly thereafter for 11 months following translocation. Hemocyte counts,
      hemocyte morphology, and hemolymph chemistry (Na+ , Cl- , Mg2+ , P3- , K+ , Ca2+
      , glucose, alanine aminotransferase, aspartate aminotransferase, and alkaline
      phosphatase]) were measured from each sample on each sampling occasion. Hemocyte
      counts were consistently greater in Q. quadrula than in A. plicata following
      transfer to captivity. Baseline hemocyte morphology and hemolymph chemistry
      varied between species. This study provides a foundation of reference ranges for
      hemocyte characterization for Q. quadrula, and A. plicata and a preliminary
      understanding of how hemocyte character might be expected to change when wild
      mussels are translocated into captivity, and thus be a useful technique for
      monitoring the health of freshwater mussels.

PMID- 29364540
TI  - Tactile stimulation during neonatal transition and its effect on vital parameters
      in neonates during neonatal transition.
AB  - AIM: This study analysed tactile stimulation during neonatal transition and
      resuscitation in preterm and term neonates born by Caesarean delivery. It
      examined the frequency, location and body region, duration and possible effects
      of stimulation on heart rate and arterial oxygen saturation (SpO2 ). METHODS: Two
      independent investigators analysed video recordings of tactile stimulation on
      term and preterm neonates during neonatal transition from January 2012 to
      December 2014. They were recorded during a prospective observational study and
      randomised controlled trial at a tertiary centre, the Medical University of Graz,
      Austria. SpO2 and heart rate were continuously recorded. Data on the frequency,
      body region and duration of stimulation were collected. To investigate the
      possible effects of stimulation, SpO2 and heart rate were compared before and
      after stimulation. RESULTS: Term infants received tactile stimulation more than
      once, and it tended to start later, last longer and be applied in more locations
      than in preterm infants. Only preterm infants showed a significant increase in
      SpO2 after stimulation and heart rates did not show any significant changes in
      either group. CONCLUSION: Tactile stimulation was applied in different ways to
      preterm and term infants during neonatal transition and SpO2 showed a significant
      increase in preterm infants.

PMID- 29364541
TI  - Cross-sectional study of randomly selected 18-year-old students showed that body
      mass index was only associated with sleep duration in girls.
AB  - AIM: This study investigated the associations, by sex, between sleep and
      adiposity, dietary habits, cardiorespiratory fitness and metabolic risk in 18
      year-old students. METHODS: We carried out a cross-sectional study of 199
      randomly chosen, healthy 18-year-old students (53% girls) in Iceland's capital
      region. The data collection took place in the winter months of 2012 to 2015. The
      anthropometric measurements were body mass index, waist circumference and body
      fat percentage. Sleep duration and dietary habits were self-reported.
      Cardiorespiratory fitness was measured on a stationary bicycle. A subsample of
      152 participants gave blood samples. RESULTS: A quarter of the adolescents failed
      to reach the minimum recommended sleep duration of seven hours per night on
      weekdays. In girls, the average sleep score was associated with body mass index
      and waist circumference, after adjusting for cardiorespiratory fitness and
      unhealthy eating scores. In boys, the average sleep score was not associated with
      anthropometric measurements, but cardiorespiratory fitness was an independent
      predictor (p < 0.001). No associations were found between average sleep scores
      and metabolic profiles in either sex. CONCLUSION: Sleep duration and adiposity
      only appeared to be associated in girls and were independent of cardiorespiratory
      fitness and unhealthy eating. Sleep duration was not related to metabolic risk.

PMID- 29364543
TI  - Measuring Clinical Supervision; how beneficial is yours and how do you know?

PMID- 29364542
TI  - Drug-induced aseptic meningitis: a mini-review.
AB  - Aseptic meningitis associates a typical clinical picture of meningitis with the
      absence of bacterial or fungal material in the cerebrospinal fluid. Drug-induced
      aseptic meningitis (DIAM) may be due to two mechanisms: (i) a direct meningeal
      irritation caused by the intrathecal administration of drugs and (ii) an
      immunologic hypersensitivity reaction to a systemic administration. If the direct
      meningeal irritation allows a rather easy recognition, the immunologic
      hypersensitivity reaction is a source of challenging diagnostics. DIAM linked to
      a systemic treatment exerts typically an early onset, usually within a week. This
      period can be shortened to a few hours in case of drug rechallenge. The fast and
      spontaneous regression of clinical symptoms is usual after stopping the suspected
      drug. Apart from these chronological aspects, no specific clinical or biological
      parameters are pathognomonic. CSF analysis usually shows pleiocytosis. The
      proteinorachia is increased while glycorachia remains normal. Underlying
      pathologies can stimulate the occurrence of DIAM. Thus, systemic lupus
      erythematosus appears to promote DIAM during NSAID therapy, especially ibuprofen
      based one. Similarly, some patients with chronic migraine are prone to
      intravenous immunoglobulin-induced aseptic meningitis. DIAM will be mainly evoked
      on chronological criteria such as rapid occurrence after initiation, rapid
      regression after discontinuation, and recurrence after rechallenge of the
      suspected drug. When occurring, positive rechallenge may be very useful in the
      absence of initial diagnosis. Finally, DIAM remains a diagnosis of elimination.
      It should be suggested only after all infectious causes have been ruled out.

PMID- 29364544
TI  - Hematology and serum biochemistry of free-ranging and captive Sechuran foxes
      (Lycalopex sechurae).
AB  - BACKGROUND: Hematologic and serum biochemical reference values obtained from
      captive or free-ranging wildlife populations may not be comparable as there can
      be significant variations due to preanalytic and analytic differences, including
      methods of capture and restraint, overall management in captivity including diet
      and composition of animal groups, and analytic methods being used. Hematology and
      serum biochemistry have never been studied in captive or free-ranging populations
      of Sechuran foxes (Lycalopex sechurae). OBJECTIVES: The purposes of the study
      were to determine hematologic and serum biochemical RI in Sechuran foxes and to
      explore differences in these variables related to sex and overall life
      circumstances. METHODS: Blood samples were obtained from 15 free-ranging and 15
      captive Sechuran foxes. Hematology variables were assessed by blood smear
      examination and automated analyzer methodology. Serum biochemical analysis was
      performed by automated analyzer methodology. Descriptive statistics were
      calculated for each variable. Data obtained from free-ranging and captive groups
      were statistically compared and RIs were calculated. RESULTS: Captive Sechuran
      foxes had significantly (P < .05) higher MCH, MCHC, and eosinophil counts and
      significantly lower band neutrophil counts than free-ranging foxes. Free-ranging
      Sechuran foxes had significantly (P < .05) higher serum lipase and globulins and
      significantly lower albumin, total bilirubin, and indirect bilirubin than captive
      foxes. CONCLUSIONS: These findings suggest that there are hematologic and serum
      biochemical differences between captive and free-ranging Sechuran fox
      populations. Hence, such differences should be considered when using these
      variables to assess the health status of this species.

PMID- 29364545
TI  - Influence of excessive exercise on immunity, metabolism, and gut microbial
      diversity in an overtraining mice model.
AB  - The purpose of this study was to evaluate the negative influence of excessive
      exercise on immunity, substance and energy metabolism as well as gut microbiota
      in mice. Firstly, an overtraining model of Male Kunming mice was established by
      high-intensity swimming exercise for 4 weeks. Then, a series of evaluation
      indicators, including the routine blood analysis, immune organ coefficient,
      digestive enzymes, and aquaporins expression levels of small intestine and colon
      tissue, histological examinations of liver, spleen, small intestine, and colon,
      were determined based on this model. Furthermore, 16S rRNA gene sequencing was
      also employed to measure the microbial composition in gut. The results found that
      immune parameters, substance and energy metabolism of all mice was altered and
      disturbed after high-intensity swimming for 4 weeks, led to an atrophy of thymus
      and spleen as well as abnormal structural changes in liver when compared to non
      swimming mice. Besides, excessive swimming mice had lower microbial diversity
      compared to non-swimming mice. However, there was no significant difference in
      gut microbial taxa between the two groups. The data indicated that excessive
      exercise exhibits negative impacts on immunity, substance and energy metabolism
      as well as gut microbial diversity.

PMID- 29364546
TI  - Use of antibiotic envelopes to prevent cardiac implantable electronic device
      infections: A meta-analysis.
AB  - INTRODUCTION: The rates of cardiac implantable electronic device (CIED)
      infections have risen over the past decade and are associated with increased
      hospitalizations and mortality. A number of preventative strategies have been
      developed including an antibiotic coated envelope, but it has yet to gain
      widespread use. METHODS: A meta-analysis was performed on controlled studies of
      the antibiotic envelope. PubMed and Google Scholar were searched for studies
      comparing infection rates with and without the use of an antibiotic envelope.
      Studies including both new implants and pulse generator replacements were
      included in the analysis. RESULTS: Five studies were included in the meta
      analysis. A total of 4,490 patients underwent CIED implantation, 1,798 with an
      antibiotic envelope and 2,692 without an envelope. In the pooled cohort, the
      envelope was associated with a 69% relative risk reduction in CIED infection
      (0.31 [0.17, 0.58] 95% CI, P = 0.0002). Propensity matched data from three
      studies were analyzed to ensure accurate comparison. In the risk-matched cohort,
      infections were significantly lower in the envelope group (3 vs. 26, P < 0.0003).
      CONCLUSION: The use of antibiotic envelopes in CIED implant is associated with a
      significantly lower rate of infection.

PMID- 29364547
TI  - The genetic architecture of nodal root number in maize.
AB  - The maize nodal root system plays a crucial role in the development of the
      aboveground plant and determines the yield via the uptake of water and nutrients
      in the field. However, the genetic architecture of the maize nodal root system is
      not well understood, and it has become the 'dark matter' of maize genetics. Here,
      a large teosinte-maize population was analyzed, and high-resolution mapping
      revealed that 62 out of 133 quantitative trait loci (QTLs), accounting for
      approximately half of the total genetic variation in nodal root number, were
      derived from QTLs for flowering time, which was further validated through a
      transgenic analysis and a genome-wide association study. However, only 16% of the
      total genetic variation in nodal root number was derived from QTLs for plant
      height. These results gave a hint that flowering time played a key role in
      shaping nodal root number via indirect selection during maize domestication. Our
      results also supported that more aerial nodal roots and fewer crown roots might
      be favored in temperate maize, and this root architecture might efficiently
      improve root-lodging resistance and the ability to take up deep water and
      nitrogen under dense planting.

PMID- 29364549
TI  - Dipeptidyl Peptidase-4 Inhibitors and Heart Failure Exacerbation in the Veteran
      Population: An Observational Study.
AB  - OBJECTIVES: The dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are
      effective modulators of fasting and postprandial hyperglycemia in patients with
      type 2 diabetes mellitus (T2DM). In 2013 the Saxagliptin Assessment of Vascular
      Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial
      Infarction 53 (SAVOR-TIMI 53) clinical trial found an increased risk of heart
      failure exacerbation, as a secondary outcome, among patients treated with
      saxagliptin. This study examines the safety of DPP-4 inhibitors as a class in
      T2DM in relation to risk of heart failure exacerbations. METHODS: Retrospective
      cohort study of two groups of patients using data from the national Department of
      Veteran's Affairs (VA) Health Care System: patients initially prescribed DPP-4
      inhibitors with or without second-generation sulfonylureas and/or metformin
      (exposed group) compared with patients initially prescribed only second
      generation sulfonylureas and/or metformin (unexposed group) between August 1,
      2013, and August 30, 2016. The primary aim of this study was to determine the
      difference in 1-year heart failure exacerbation rate in patients with T2DM
      between the exposed and unexposed groups. Data were analyzed using the chi2
      Student t test and Kaplan-Meier analysis. Significance was set at p<0.05.
      RESULTS: The study evaluated 672,265 patients: 33,614 patients in the exposed
      group and 638,651 patients in the unexposed group. Overall, 130 (0.38%) heart
      failure exacerbations were documented in the exposed group, and 2222 (0.34%)
      heart failure exacerbations were documented in the unexposed group; the
      difference in exacerbation rate was nonsignificant between groups (p=0.24). In a
      subgroup analysis of patients with a baseline diagnosis of heart failure, the
      difference in rate of heart failure exacerbations remained nonsignificant
      (p=0.334). CONCLUSIONS: Patients in the veteran population with T2DM treated with
      DPP-4 inhibitors did not demonstrate a significant increase in risk for heart
      failure exacerbation, regardless of whether a patient had been previously
      diagnosed with heart failure. This finding potentially supports safe usage of DPP
      4 inhibitors in this patient population regardless of heart failure diagnosis.

PMID- 29364548
TI  - Efficacy of micafungin for the treatment of invasive candidiasis and candidaemia
      in patients with neutropenia.
AB  - Neutropenia is linked to the development of invasive candidiasis/candidaemia, for
      which micafungin has demonstrated efficacy, but evidence in patients with
      neutropenia is limited. The aim of this study was to evaluate the efficacy of
      micafungin for the treatment of invasive candidiasis/candidaemia in patients with
      neutropenia (<500 neutrophils/MUL) and without neutropenia. This pooled, post hoc
      analysis of 2 Phase 3 trials compared micafungin 100 mg/d (adults) and 2 mg/kg/d
      (paediatrics) with L-AmB 3 mg/kg/d (NCT00106288) and micafungin 100 mg/d and 150
      mg/d with caspofungin 70 mg/d followed by 50 mg/d (adults) (NCT00105144);
      treatment duration 2-4 weeks (<=8 weeks for chronic disseminated candidiasis).
      Effects of neutropenia duration and Candida spp. on efficacy outcomes (treatment
      success, clinical and mycological response) were examined. Of 685 patients, 77
      had neutropenia. The most common infection in patients with/without neutropenia
      was due to C. tropicalis (31/77) and C. albicans (295/608) respectively. Overall
      success was numerically lower in patients with vs without neutropenia (63.6% vs
      72.9%). Clinical and mycological response was similar between groups. Neutropenia
      duration or Candida spp. did not impact micafungin's overall success rate. This
      analysis supports evidence that micafungin is effective against invasive
      candidiasis/candidaemia in patients with neutropenia, irrespective of neutropenia
      duration or Candida spp., although overall success may be lower than in patients
      without neutropenia.

PMID- 29364550
TI  - Probing Cyclic pi-Electron Delocalization in an Imidazol-2-ylidene and a
      Corresponding Imidazolium Salt.
AB  - The extent of cyclic pi-electron delocalization in the N-heterocyclic ring of an
      imidazol-2-ylidene (i.e., 1,3,4,5-tetramethylimidazol-2-ylidene) and its
      corresponding imidazolium salt (i.e., 1,3,4,5-tetramethylimidazolium chloride)
      has been investigated theoretically by using Bader's quantum theory of atoms in
      molecules (QTAIM) descriptors, delocalization indices, electron localizability
      indicators (ELI-Ds), and the source function tool. In addition, the experimental
      electron density distribution for the imidazolium salt has been obtained and
      analyzed from 100 K X-ray diffraction data. A significant drop is found in the
      ellipticity of the electron density along the Ccarbene -N bond path in the
      imidazol-2-ylidene. This is shown to be a natural consequence of the sigma lone
      pair of the Ccarbene atom, which overwhelms the pi-electron density, rather than
      a sign of a significantly diminished degree of pi-electron delocalization in the
      imidazol-2-ylidene compared to its imidazolium salt. In fact, the source
      functions, the ELI-Ds, and the delocalization indices all probe a quite similar
      extent of cyclic pi-electron delocalization in the N-heterocyclic rings of the
      two compounds.

PMID- 29364551
TI  - Acid burn attacks: Looking beneath the surface.

PMID- 29364552
TI  - Troubleshooting electromagnetic interference in a patient with centrifugal flow
      left ventricular assist device and subcutaneous implantable cardioverter
      defibrillator.
AB  - A 25-year-old man with severe nonischemic dilated cardiomyopathy underwent
      subcutaneous implantable cardioverter defibrillator (S-ICD) implant and
      subsequently underwent HeartWare ventricular assist device (HVAD) placement.
      Postoperative interrogation revealed both primary and secondary S-ICD vectors
      inappropriately regarded sinus rhythm as "noise," and the alternate vector
      significantly undersensed sinus rhythm. The S-ICD was reinterrogated using high
      resolution capture to visually confirm EMI with a dominant frequency in both the
      primary and secondary vectors of 46.67 Hz that fell within the S-ICD operational
      range of 9-60 Hz. The 46.67 Hz frequency correlated with the HVAD operational
      speed of 2,800 RPM. The HVAD pump speed was increased from 2,800 to 3,000 RPM,
      resulting in a dominant frequency of 50 Hz. The notch filter is nonprogrammable
      in S-ICDs. However, the built-in filter is 50 Hz for countries in European time
      zones as opposed to 60 Hz in US time zones due to differences in the anticipated
      noise from electrical sources within each continent. Thus, the S-ICD time zone
      was reprogrammed from EST to GMT, which reduced the notch filter from 60  to 50
      Hz, resulting in S-ICD successfully eliminating EMI when the patient was in a
      supine position. The EMI interference was still intermittently present in the
      upright patient position. This case demonstrates the utility of high-resolution
      electrogram capture to identify the source and frequency of EMI in S-ICD and
      offers a potential avenue to troubleshoot dominant frequency oversensing by
      changing the device time zone.

PMID- 29364553
TI  - Assessing relative cost of complications following orthotopic liver transplant.
AB  - INTRODUCTION: Perioperative complications impose both a clinical and financial
      burden on patients and the healthcare system. This study sought to identify the
      frequency and economic impact of complications following orthotopic liver
      transplantation (OLT). METHODS: The Premier Perspective(r) Hospital Database was
      queried for patients undergoing OLT between 2008 and 2015. Complications were
      identified by ICD-9 code and grouped by complication type. Complication frequency
      as well as impact on clinical and economic outcomes was calculated. Complication
      frequency and effect on cost were combined to determine the annual impact of each
      complication type on perioperative OLT cost. RESULTS: Among 2747 OLT patients,
      the most common groups of complications following OLT were pulmonary, bleeding,
      and infectious. The complications with the greatest average effect on treatment
      related costs were infectious, neurologic, deep vein thrombosis/pulmonary
      embolus, and hepatic arterial thrombosis. Infectious, pulmonary, and bleeding
      complications had the greatest annual effect on perioperative OLT cost.
      CONCLUSIONS: Efforts focused on preventing coagulopathic bleeding, improving post
      operative pulmonary toilet, and minimizing sources of infection can help improve
      the cost-effectiveness of OLT. Additionally, the combination of these cost data
      and systematized protocols can help insurers construct bundled payments for OLT
      that more accurately reflect the cost of perioperative transplant care.

PMID- 29364554
TI  - Validation of a novel mapping system and utility for mapping complex atrial
      tachycardias.
AB  - INTRODUCTION: This study sought to validate a novel wavefront mapping system
      utilizing whole-chamber basket catheters (CARTOFINDER, Biosense Webster). The
      system was validated in terms of (1) mapping atrial-paced beats and (2) mapping
      complex wavefront patterns in atrial tachycardia (AT). METHODS AND RESULTS:
      Patients undergoing catheter ablation for AT and persistent AF were included. A
      64-pole-basket catheter was used to acquire unipolar signals that were processed
      by CARTOFINDER mapping system to generate dynamic wavefront propagation maps. The
      left atrium was paced from four sites to demonstrate focal activation. ATs were
      mapped with the mechanism confirmed by conventional mapping, entrainment, and
      response to ablation. Twenty-two patients were included in the study (16 with AT
      and 6 with AF initially who terminated to AT during ablation). In total, 172 maps
      were created with the mapping system. It correctly identified atrial-pacing sites
      in all paced maps. It accurately mapped 9 focal/microreentrant and 18
      macroreentrant ATs both in the left and right atrium. A third and fourth observer
      independently identified the sites of atrial pacing and the AT mechanism from the
      CARTOFINDER maps, while being blinded to the conventional activation maps.
      CONCLUSIONS: This novel mapping system was effectively validated by mapping focal
      activation patterns from atrial-paced beats. The system was also effective in
      mapping complex wavefront patterns in a range of ATs in patients with scarred
      atria. The system may therefore be of practical use in the mapping and ablation
      of AT and could have potential for mapping wavefront activations in AF.

PMID- 29364555
TI  - Community study found that cutaneous allergies in childhood were associated with
      conduct problems in girls.

PMID- 29364556
TI  - Commentary on a paper by Holden et al.

PMID- 29364557
TI  - Genome-wide single nucleotide polymorphism-based autozygosity mapping facilitates
      identification of mutations in consanguineous families with epidermolysis
      bullosa.
AB  - Autozygosity mapping (AM) is a technique utilised for mapping homozygous
      autosomal recessive (AR) traits and facilitation of genetic diagnosis. We
      investigated the utility of AM for the molecular diagnosis of heterogeneous AR
      disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this
      technique to a cohort of 46 distinct EB families using both short tandem repeat
      (STR) and genome-wide single nucleotide polymorphism (SNP) array-based AM to
      guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46
      cases were diagnosed with homozygous mutations using this method. Independently,
      26 cases, including the seven initially unresolved cases, were analysed with an
      EB-targeted next-generation sequencing (NGS) panel. NGS identified mutations in
      five additional cases, initially undiagnosed due to the presence of compound
      heterozygosity, deep intronic mutations or runs of homozygosity below the set
      threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7%) diagnosed
      genetically.

PMID- 29364558
TI  - A Crosslinked Nucleic Acid Nanogel for Effective siRNA Delivery and Antitumor
      Therapy.
AB  - Functional siRNAs are employed as cross-linkers to direct the self-assembly of
      DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized
      hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs)
      are fully embedded and protected for systemic delivery. Owing to the existence of
      multivalent mutual crosslinking events inside, the crosslinked nanogels with
      tunable size exhibit not only good thermostability, but also remarkable
      physiological stability that can resist the enzymatic degradation. As a novel
      siRNA delivery system with spherical nucleic acid (SNA) architecture, the
      crosslinked nanogels can assist the delivery of siRNAs into different cells
      without any transfection agents and achieve the gene silencing effectively both
      in vitro and in vivo, through which a significant inhibition of tumor growth is
      realized in the anticancer treatment.

PMID- 29364560
TI  - Endoanal resection of a giant villous adenoma in the middle rectum - a video
      vignette.

PMID- 29364559
TI  - A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics
      of peroxisomes.
AB  - Peroxisomes are dynamic organelles which fulfil essential roles in lipid and ROS
      metabolism. Peroxisome movement and positioning allows interaction with other
      organelles and is crucial for their cellular function. In mammalian cells, such
      movement is microtubule-dependent and mediated by kinesin and dynein motors. The
      mechanisms of motor recruitment to peroxisomes are largely unknown, as well as
      the role this plays in peroxisome membrane dynamics and proliferation. Here,
      using a combination of microscopy, live-cell imaging analysis and mathematical
      modelling, we identify a role for Mitochondrial Rho GTPase 1 (MIRO1) as an
      adaptor for microtubule-dependent peroxisome motility in mammalian cells. We show
      that MIRO1 is targeted to peroxisomes and alters their distribution and motility.
      Using a peroxisome-targeted MIRO1 fusion protein, we demonstrate that MIRO1
      mediated pulling forces contribute to peroxisome membrane elongation and
      proliferation in cellular models of peroxisome disease. Our findings reveal a
      molecular mechanism for establishing peroxisome-motor protein associations in
      mammalian cells and provide new insights into peroxisome membrane dynamics in
      health and disease.

PMID- 29364561
TI  - Analysis of NTPDase2 in the cell membrane using fluorescence recovery after
      photobleaching (FRAP).
AB  - NTPDase2, a member of the CD39/NTPDase family, is an ecto-nucleotidase anchored
      to the plasma membrane by two transmembrane domains, with a catalytic site facing
      the extracellular space and preferentially hydrolyzing nucleoside triphosphates.
      While NTPDase2 is expressed in many cell types, its unique functionality,
      mobility and dynamics at the cell membrane remain unexplored. We therefore
      constructed a recombinant NTPDase2 linked to the yellow fluorescent protein
      (EYFP) to investigate its dynamics by confocal microscopy. The present study
      shows that the expression of EYFP-NTPDase2 in different cell lines does not
      affect its proliferation, migration and adhesion to extracellular matrices (ECM).
      Moreover, in human embryonic kidney cells 293 (HEK293) grown on collagen type I
      and fibronectin, EYFP-NTPDase2 fluorescence is greater in free plasma membrane
      regions than in cell-cell contacts, in comparison with cells grown on other
      substrates. Differences in the time required for fluorescence recovery after
      photobleaching (FRAP) in free membrane regions and cell-cell contacts indicate
      that the mobility of EYFP-NTPDase2 depends on the matrix to which the cells are
      attached. (c) 2018 International Society for Advancement of Cytometry.

PMID- 29364562
TI  - Logging disturbance shifts net primary productivity and its allocation in Bornean
      tropical forests.
AB  - Tropical forests play a major role in the carbon cycle of the terrestrial
      biosphere. Recent field studies have provided detailed descriptions of the carbon
      cycle of mature tropical forests, but logged or secondary forests have received
      much less attention. Here, we report the first measures of total net primary
      productivity (NPP) and its allocation along a disturbance gradient from old
      growth forests to moderately and heavily logged forests in Malaysian Borneo. We
      measured the main NPP components (woody, fine root and canopy NPP) in old-growth
      (n = 6) and logged (n = 5) 1 ha forest plots. Overall, the total NPP did not
      differ between old-growth and logged forest (13.5 +/- 0.5 and 15.7 +/- 1.5 Mg C
      ha-1  year-1 respectively). However, logged forests allocated significantly
      higher fraction into woody NPP at the expense of the canopy NPP (42% and 48% into
      woody and canopy NPP, respectively, in old-growth forest vs 66% and 23% in logged
      forest). When controlling for local stand structure, NPP in logged forest stands
      was 41% higher, and woody NPP was 150% higher than in old-growth stands with
      similar basal area, but this was offset by structure effects (higher gap
      frequency and absence of large trees in logged forest). This pattern was not
      driven by species turnover: the average woody NPP of all species groups within
      logged forest (pioneers, nonpioneers, species unique to logged plots and species
      shared with old-growth plots) was similar. Hence, below a threshold of very heavy
      disturbance, logged forests can exhibit higher NPP and higher allocation to wood;
      such shifts in carbon cycling persist for decades after the logging event. Given
      that the majority of tropical forest biome has experienced some degree of
      logging, our results demonstrate that logging can cause substantial shifts in
      carbon production and allocation in tropical forests.

PMID- 29364563
TI  - Reply to 'Comments on a new classification, treatment algorithm and prognosis
      estimating system for sigmoid volvulus: the role of percutaneous endoscopic
      colostomy (PEC)'.

PMID- 29364565
TI  - Violencia De Pareja (Intimate Partner Violence).

PMID- 29364564
TI  - Precisely Tailoring Upconversion Dynamics via Energy Migration in Core-Shell
      Nanostructures.
AB  - Upconversion emission dynamics have long been believed to be determined by the
      activator and its interaction with neighboring sensitizers. Herein this
      assumption is, however, shown to be invalid for nanostructures. We demonstrate
      that excitation energy migration greatly affects upconversion emission dynamics.
      "Dopant ions' spatial separation" nanostructures are designed as model systems
      and the intimate link between the random nature of energy migration and
      upconversion emission time behavior is unraveled by theoretical modelling and
      confirmed spectroscopically. Based on this new fundamental insight, we have
      successfully realized fine control of upconversion emission time behavior (either
      rise or decay process) by tuning the energy migration paths in various
      specifically designed nanostructures. This result is significant for applications
      of this type of materials in super resolution spectroscopy, high-density data
      storage, anti-counterfeiting, and biological imaging.

PMID- 29364566
TI  - Effects of higher versus lower threat contexts on pain-related attention biases:
      An eye-tracking study.
AB  - BACKGROUND: Threat is hypothesized to affect the degree to which pain captures
      attention but little is known about its impact on dynamic courses of attention
      towards pain. In this eye-tracking study, we evaluated pain-related visual
      attention biases during image pair presentations in comparatively lower versus
      higher threat conditions. METHODS: Gaze biases of healthy adults (47 women, 35
      men) were assessed during image presentation phases standardized across (1) a
      modified visual dot-probe task featuring painful-neutral (pain) and neutral
      neutral contrast (neutral) image pair blocks (lower threat context); and (2) an
      impending pain task wherein the same image pair blocks, respectively, cued
      potentially painful postoffset somatosensory stimuli (higher threat context) and
      its absence. RESULTS: Across tasks, participants were more often oriented
      towards, gazed longer at, and fixated more times on pain images in pain block
      trials, although trait fear of pain was not related to any gaze biases.
      Critically, however, participants reported more state fear and displayed
      significantly fewer initial fixations, longer first and overall gaze durations,
      and more unique fixations on pain images when image pairs signalled possible
      postoffset pain stimulation. CONCLUSIONS: Results underscored stronger overall
      attention maintenance on visual pain cues in a higher threat (impending pain)
      context. SIGNIFICANCE: Through considering gaze parameters during image
      presentation phases of dot-probe and impending pain tasks, possible effects of
      lower versus higher threat contexts on attention biases were elucidated.
      Participants reported more fear and gazed longer at painful than neutral images
      in the higher threat context whereby image pairs cued possible pain.

PMID- 29364568
TI  - Effect of different immobilization strategies on chiral recognition properties of
      Cinchona-based anion exchangers.
AB  - In the enantiomeric separation of highly polar compounds, a traditionally
      challenging task for high-performance liquid chromatography, ion-exchange chiral
      stationary phases have found the main field of application. In this contribution,
      we present a series of novel anion-exchange-type chiral stationary phases for
      enantiomer separation of protected amino phosphonates and N-protected amino
      acids. Two of the prepared selectors possessed a double and triple bond within a
      single molecule. Thus, they were immobilized onto silica support employing either
      a thiol-ene (radical) or an azide-yne (copper(I)-catalyzed) click reaction. We
      evaluated the selectivity and the effect of immobilization proceeding either by
      the double bond of the Cinchona alkaloid or a triple bond of the carbamoyl moiety
      on the chromatographic performance of the chiral stationary phases using analytes
      with protecting groups of different size, flexibility, and pi-acidity. The
      previously observed preference toward protecting groups possessing pi-acidic
      units, which is a typical feature of Cinchona-based chiral stationary phases, was
      preserved. In addition, increasing the bulkiness of the selectors' carbamoyl
      units leads to significantly reduced retention times, while very high selectivity
      toward the tested analytes is retained.

PMID- 29364569
TI  - Lignocellulose Liquefaction to Biocrude: A Tutorial Review.
AB  - After 40 years of research and development, liquefaction technologies are now
      being demonstrated at 200-3000 tons per year scale to convert lignocellulosic
      biomass to biocrudes for use as heavy fuel or for upgrading to biofuels. This
      Review attempts to present the various facets of the liquefaction process in a
      tutorial manner. Emphasis is placed on liquefaction in high-boiling solvents,
      with regular reference to liquefaction in subcritical water or other light
      boiling solvents. Reaction chemistry, solvent selection, role of optional
      catalyst as well as biocrude composition and properties are discussed in depth.
      Challenges in biomass feeding and options for biocrude-solvent separation are
      addressed. Process concepts are reviewed and demonstration/commercialization
      efforts are presented.

PMID- 29364570
TI  - Geographic and racial representation and reported success rates of studies of
      catheter ablation for atrial fibrillation: Findings from the SMASH-AF meta
      analysis study cohort.
AB  - INTRODUCTION: We performed a systematic review and meta-analysis of geographic
      and racial representation and reported success rates of studies of catheter
      ablation for atrial fibrillation (AF). METHODS AND RESULTS: We searched PubMed,
      Scopus, and Cochrane databases from 1/1/1990 to 8/1/2016 for trials and
      observational studies reporting AF ablation outcomes. Major exclusion criteria
      were insufficient reporting of outcomes, non-English language articles, and
      ablation strategies that were not prespecified and uniform. We described
      geographic and racial representation and single-procedure ablation success rates
      by country, controlling for patient demographics and study design
      characteristics. The analysis cohort included 306 studies (49,227 patients) from
      28 countries. Over half of the paroxysmal (PAF) and nonparoxysmal AF (NPAF)
      treatment arms were conducted in 5 and 3 countries, respectively. Reporting of
      race or ethnicity demographics and outcomes were rare (1 study, 0.3%) and
      nonexistent, respectively. Unadjusted success rates by country ranged from 63.5%
      to 83.0% for PAF studies and 52.7% to 71.6% for NPAF studies, with substantial
      variation in patient demographics and study design. After controlling for
      covariates, South Korea and the United States had higher PAF ablation success
      rates, with large residual heterogeneity. NPAF ablation success rates were
      statistically similar by country. CONCLUSIONS: Studies of AF ablation have
      substantial variation in patient demographics, study design, and reported
      outcomes by country. There is limited geographic representation of trials and
      observational studies of AF ablation and a paucity of race- or ethnicity
      stratified results. Future AF ablation studies and registries should aim to have
      broad representation by race, geography, and ethnicity to ensure
      generalizability.

PMID- 29364571
TI  - All-in-one: The dream and reality of molecular cytopathology testing on routine
      lung cancer smears.

PMID- 29364567
TI  - The role of monocytosis and neutrophilia in atherosclerosis.
AB  - Monocytosis and neutrophilia are frequent events in atherosclerosis. These
      phenomena arise from the increased proliferation of hematopoietic stem and
      multipotential progenitor cells (HSPCs) and HSPC mobilization from the bone
      marrow to other immune organs and circulation. High cholesterol and inflammatory
      signals promote HSPC proliferation and preferential differentiation to the
      myeloid precursors (i.e., myelopoiesis) that than give rise to pro-inflammatory
      immune cells. These cells accumulate in the plaques thereby enhancing vascular
      inflammation and contributing to further lesion progression. Studies in animal
      models of atherosclerosis showed that manipulation with HSPC proliferation and
      differentiation through the activation of LXR-dependent mechanisms and
      restoration of cholesterol efflux may have a significant therapeutic potential.

PMID- 29364572
TI  - Intermediate-severity wind disturbance in mature temperate forests: legacy
      structure, carbon storage, and stand dynamics.
AB  - Wind is one of the most important natural disturbances influencing forest
      structure, ecosystem function, and successional processes worldwide. This study
      quantifies the stand-scale effects of intermediate-severity windstorms (i.e.,
      blowdowns) on (1) live and dead legacy structure, (2) aboveground carbon storage,
      and (3) tree regeneration and associated stand dynamics at four mature, mixed
      hardwood-conifer forest sites in the northeastern United States. We compare wind
      affected forests to adjacent reference conditions (i.e., undisturbed portions of
      the same stands) 0-8 yr post-blowdown using parametric (ANOVA) and nonparametric
      (NMS ordination) analyses. We supplement inventory plots and downed coarse woody
      detritus (DCWD) transects with hemispherical photography to capture spatial
      variation in the light environment. Although recent blowdowns transferred a
      substantial proportion of live overstory trees to DCWD, residual live tree basal
      area was high (19-59% of reference areas). On average, the initial post-blowdown
      ratio of DCWD carbon to standing live tree carbon was 2.72 in blowdown stands and
      0.18 in reference stands, indicating a large carbon transfer from live to dead
      pools. Despite these dramatic changes, structural complexity remained high in
      blowdown areas, as indicated by the size and species distributions of overstory
      trees, abundance of sound and rotten downed wood, spatial patterns of light
      availability, and variability of understory vegetation. Furthermore, tree species
      composition was similar between blowdown and reference areas at each site, with
      generally shade-tolerant species dominating across multiple canopy strata.
      Community response to intermediate-severity blowdown at these sites suggests a
      dynamic in which disturbance maintains late-successional species composition
      rather than providing a regeneration opportunity for shade-intolerant, pioneer
      species. Our findings suggest that intermediate-severity wind disturbances can
      contribute to stand-scale structural complexity as well as development toward
      late-successional species composition, at least when shade-tolerant regeneration
      is present pre-blowdown. Advance regeneration thus enhances structural and
      compositional resilience to this type of disturbance. This study provides a
      baseline for multi-cohort silvicultural systems designed to restore heterogeneity
      associated with natural disturbance dynamics.

PMID- 29364573
TI  - Comment on a paper by Von Dincklage et al. entitled 'Higher doses of
      intraoperative analgesia are associated with lower levels of persistent pain and
      less analgesic consumption six months after total hip arthroplasty'.

PMID- 29364574
TI  - Simultaneous determination of seven phenylethanoid glycosides in Cistanches Herba
      by a single marker using a new calculation of relative correction factor.
AB  - Current quantitative analysis of multi-components by a single marker is usually
      performed by using liquid chromatography methods coupled with ultraviolet or mass
      spectrometry detection to afford the relative correction factors between
      reference standard and other components. However, low durability of the relative
      correction factors caused by different chromatographic system leading this
      approach lacking a high accuracy. In the present study, a simple but effective
      method was established by employing the absorption coefficient (E1 cm 1%) to
      calculate the relative correction factors instead of peak area or height. The
      absorption coefficient, a fundamental constant of physics, has been widely used
      for qualitative and quantitative analysis in Pharmacopoeia all over the world.
      According to the absorbance coefficient ratio between echinacoside and other
      compounds, the content of seven phenylethanoid glycosides in Cistanche
      deserticola and Cistanches tubulosa were determined simultaneously. The low
      standard method difference on quantitative measurement of seven compounds in
      Cistanches Herba between our method and the external standard method proved the
      consistency of the two methods. Using an ultra high performance liquid system,
      these seven bioactive phenylethanoid glycosides were baseline separated in 8 min.
      All the data suggested that the method was accurate and reliable for the
      determination of multi-components when authentic standard substances were
      unavailable.

PMID- 29364575
TI  - Childbirth Fear: Relation to Birth and Care Provider Preferences.
AB  - INTRODUCTION: The purpose of this study was to assess how preferences for place
      of birth and mode of birth relate to different dimensions of childbirth fear and
      whether there is an association between Canadian women's prenatal fear of
      childbirth and the type and quality of prenatal care they received. METHODS: A
      link to an online survey was posted on Canadian pregnancy and birth websites; 409
      women completed the survey that included sociodemographic questions, questions
      about the current pregnancy and previous pregnancy experiences (if applicable),
      and the Childbirth Fear Questionnaire, a validated 40-item scale that measures 9
      dimensions of childbirth fear. RESULTS: Women under physician care and those with
      a preference for cesarean birth were generally more fearful of pain associated
      with vaginal birth, fear of loss of sexual pleasure and attractiveness, and fear
      of harm to themselves or their infant. Conversely, women under the care of
      midwives and women who preferred to give birth vaginally were more fearful of
      interventions. Women who preferred a cesarean birth were significantly more
      likely to report that fear of childbirth interfered with daily functioning,
      compared to women who preferred a vaginal birth. Satisfaction with care was
      associated with lower scores on the Childbirth Fear Questionnaire full and
      subscales, especially among midwifery clients. DISCUSSION: At present there are
      no guidelines in Canada or the United States for the treatment and/or referral of
      pregnant women who suffer from childbirth fear. Until such guidelines are
      developed, findings from the current study can help maternity care providers
      identify and address specific fears among women in their care and understand how
      different fear domains relate to care provider choice, satisfaction with care,
      and women's preferences for place and mode of birth.

PMID- 29364576
TI  - Simultaneous detection of single-nucleotide variant, deletion/insertion, and
      fusion in lung and thyroid carcinoma using cytology specimen and an RNA-based
      next-generation sequencing assay.
AB  - BACKGROUND: Molecular testing for epidermal growth factor receptor (EGFR)
      mutation and anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1, receptor
      tyrosine kinase (ROS1) fusion is routinely performed in patients with stage IV
      lung adenocarcinoma to assess their eligibility for targeted therapy. Fine-needle
      aspiration (FNA)-derived material frequently is the only pathologic material
      available. The identification of genomic aberrations in thyroid nodules from FNA
      smears may help stratify cancer risk and spare patients from a second surgery. In
      the current study, the authors tested nucleic acid extracted from the cytology
      smears of lung and thyroid carcinomas for simultaneous detection of single
      nucleotide variant, insertion/deletion, and gene fusion using an RNA-based next
      generation sequencing assay. METHODS: A total of 27 cases (17 lung and 10 thyroid
      carcinomas, the majority of which had known variants) were tested. Areas of
      interest were scrapped from stained smears using a scalpel. Total nucleic acid
      was extracted. Gene fusion and mutational analysis was performed using the
      Comprehensive Thyroid and Lung FusionPlex Assay. Data were analyzed using the
      analysis pipeline provided by the vendor. Eleven cases with available formalin
      fixed, paraffin-embedded (FFPE) tissue were tested in parallel. RESULTS: Gene
      fusions were detected in 6 cases; common single-nucleotide variants in EGFR, RAS,
      and BRAF in 14 cases; and in-frame deletions within EGFR in 3 cases. A
      concordance rate of 100% was observed between FNA and FFPE tissue. CONCLUSIONS:
      Cytology preparations can be a reliable source for the detection of both DNA and
      RNA aberrations. The ability to simultaneously detect multiple types of genomic
      variants is crucial for patients with advanced cancer and maximizes the
      usefulness of cytology specimens. Cancer Cytopathol 2018;126:158-69. (c) 2018
      American Cancer Society.

PMID- 29364577
TI  - Resolving incomplete single nucleotide polymorphism tagging of HLA-DQ2.2 for
      coeliac disease genotyping using digital droplet PCR.
AB  - A hallmark of coeliac disease (CD) is the exceptionally strong genetic
      association with HLA-DQ2.5, DQ8, and DQ2.2. HLA typing provides information on CD
      risk important to both clinicians and researchers. A method that enables simple
      and fast detection of all CD risk genotypes is particularly desirable for the
      study of large populations. Single nucleotide polymorphism (SNP)-based HLA typing
      can detect the CD risk genotypes by detecting a combination of six SNPs but this
      approach can struggle to resolve HLA-DQ2.2, seen in 4% of European CD patients,
      because of the low resolution of one negatively predicting SNP. We sought to
      optimise SNP-based HLA typing by harnessing the additional resolution of digital
      droplet PCR to resolve HLA-DQ2.2. Here we test this two-step approach in an
      unselected sample of Mexican DNA and compare its accuracy to DNA typed using
      traditional exon detection. The addition of digital droplet PCR for samples
      requiring negative prediction of HLA-DQ2.2 enabled HLA-DQ2.2 to be accurately
      typed. This technique is a simple addition to a SNP-based typing strategy and
      enables comprehensive definition of all at-risk HLA genotypes in CD in a timely
      and cost-effective manner.

PMID- 29364578
TI  - Building Zeolites from Precrystallized Units: Nanoscale Architecture.
AB  - Since the early reports by Barrer in the 1940s on converting natural minerals
      into synthetic zeolites, the use of precrystallized zeolites as crucial inorganic
      directing agents to synthesize other crystalline zeolites with improved
      physicochemical properties has become a very important research field, allowing
      the design, particularly in recent years, of new industrial catalysts. This
      Review highlights how the presence of some crystalline fragments in the synthesis
      media, such as small secondary building units (SBUs) or layered substructures,
      not only favors the crystallization of other zeolites with similar SBUs or
      layers, but also permits control over important parameters affecting their
      catalytic activity (chemical composition, crystal size, or porosity, etc.).
      Recent advances in the preparation of 3D and 2D zeolites through seeding and
      zeolite-to-zeolite transformation processes will be discussed extensively in this
      Review, including their preparation in the presence or absence of organic
      structure-directing agents (OSDAs). The aim is to introduce general guidelines
      for more efficient approaches for target zeolites.

PMID- 29364579
TI  - Effects of Milk or Apple Juice Ingestion on the Pharmacokinetics of Elvitegravir
      and Cobicistat in Healthy Japanese Male Volunteers: A Randomized, Single-Dose,
      Three-Way Crossover Study.
AB  - Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) is
      specified in its package insert to be taken with food to obtain sufficient
      exposure of EVG. It has been reported that a nutritional protein-rich drink shows
      comparable pharmacokinetics (PK) of EVG to those with a standard breakfast. In
      this study, the PK profiles of EVG and COBI were evaluated by administration of a
      single dose of EVG/COBI/FTC/TAF, after ingestion of either a nutritional protein
      rich drink, milk, or apple juice. The geometric means for Cmax and AUCinf of EVG
      following milk ingestion slightly decreased by 21% and 14%, respectively, and
      those following apple juice ingestion decreased by 67% and 61%, respectively,
      compared with a nutritional protein-rich drink. There were no differences in any
      PK parameters of COBI. Therefore, taking EVG/COBI/FTC/TAF after milk or apple
      juice ingestion appeared to be not appropriate. However, for plasma trough
      concentrations (Ctau ), it is known that Ctau is best correlated with the
      efficacy of EVG. The mean C24 of EVG after milk ingestion was 620.6 ng/mL, which
      was more than 10-fold the protein binding-adjusted 95% inhibitory concentration.
      With all the above considerations, it was concluded that taking EVG/COBI/FTC/TAF
      with milk could be an option to maintain sufficient plasma concentrations of EVG.

PMID- 29364580
TI  - HLA-A*02:01:01:28, a novel HLA allele identified by next-generation sequencing in
      a Chinese family.
AB  - HLA-A*02:01:01:28 differs from A*02:01:01:01 by one nucleotide transition, T>A
      2952 in intron 6.

PMID- 29364581
TI  - Global prevalence of exercise-induced bronchoconstriction in childhood: A meta
      analysis.
AB  - AIM: This systematic review and meta-analysis aimed to estimate the global
      prevalence of exercise-induced bronchoconstriction (EIB) in children and
      adolescents. METHOD: We searched PubMed, Google Scholar, and the Virtual Health
      Library-BIREME from inception to December 23, 2017. We selected observational
      studies that reported the prevalence of EIB (diagnosed by exercise challenge
      test) in children and adolescents aged 5-18 years. We conducted random-effects
      meta-analyses to estimate the pooled prevalence of EIB and 95% CI. RESULTS: We
      included 66 studies (55 696 participants, 5670 cases of EIB) in the review, of
      which 33 in general population of children and adolescents, 10 in child and
      adolescent athletes and 23 in children and adolescents with asthma. The global
      mean prevalence of EIB in the general population of children and adolescents was
      9% (IC95%: 8-10%), with a higher rate (12%) in Asia-Pacific and America. The mean
      prevalence of EIB was 15% (95% CI: 9-21%) in child and adolescent athletes, and
      46% (95% CI: 39-53%) in children and adolescents with asthma. We estimated that,
      globally, around 16.5 million (95% CI: 15-18 million) children and adolescents up
      to 18 years of age may have EIB. CONCLUSION: EIB in childhood should be
      considered as a global public health problem that needs more attention. The
      substantial heterogeneity between studies highlights the need for evidence-based
      guidelines for diagnosis of EIB in this age group.

PMID- 29364583
TI  - Incretins: Beyond type 2 diabetes.
AB  - While the use of incretins, including GLP-1 receptor agonists and PDD-IV
      inhibitors, is well established in the treatment of type 2 diabetes, many other
      aspects of these agents are yet to be discovered and utilized for their potential
      clinical benefit. These include the potential role of GLP-1 receptor agonists in
      the induction of weight loss, blood pressure reduction, anti-inflammatory and
      nephro- and cardio-protective actions. Their potential benefit in type 1 diabetes
      is also being investigated. This review will attempt to comprehensively describe
      novel discoveries in the field of incretin pathophysiology and pharmacology
      beyond their classical role in the treatment of type 2 diabetes.

PMID- 29364584
TI  - A review of dipeptidyl peptidase-4 inhibitors. Hot topics from randomized
      controlled trials.
AB  - The first clinical study to investigate effects of dipeptidyl peptidase-4 (DPP-4)
      inhibition was published in 2002, and since then, numerous randomized controlled
      trials (RCTs) have shown that DPP-4 inhibitors are efficacious, safe and well
      tolerated. This review will focus upon RCTs which have investigated DPP-4
      inhibitors in patient groups which are often under-represented or excluded from
      typical phase 3 clinical trials. Large cardiovascular (CV) safety outcome trials
      in patients with established CV disease have confirmed that DPP-4 inhibitors are
      not associated with any additional CV risk in these already-at-high-risk
      individuals, while raising awareness of any uncommon adverse events, such as
      heart failure hospitalization seen in one of the trials. Studies in patients with
      kidney disease have shown DPP-4 inhibitors to be efficacious without increasing
      the risk of hypoglycaemia, irrespective of the degree of renal impairment, while
      data from the large CV trials as well as smaller RCTs have even pointed towards
      potential renoprotective effects such individuals. The use of DPP-4 inhibitors
      with insulin when therapy requires intensification may be beneficial without
      affecting the incidence or severity of hypoglycaemia, with these effects also
      being replicated in patients with chronic kidney disease, for whom other agents
      may not be suitable. Attention is now turning towards exploring the potential
      utility of DPP-4 inhibitors in other circumstances, including for in-hospital
      management of hyperglycaemia and in other metabolic disorders. Together, these
      RCTs raise the possibility that in the future, DPP-4 inhibitors may have a
      broader use which may extend beyond glycaemic control in the typical type 2
      diabetes mellitus (T2DM) patient seen in general practice and may encompass
      conditions other than T2DM.

PMID- 29364582
TI  - Genome-wide scan for circulating vascular adhesion protein-1 levels: MACROD2 as a
      potential transcriptional regulator of adipogenesis.
AB  - AIMS/INTRODUCTION: Vascular adhesion protein-1 (VAP-1) is a membrane-bound amine
      oxidase highly expressed in mature adipocytes and released into the circulation.
      VAP-1 has been strongly implicated in several pathological processes, including
      diabetes, inflammation, hypertension, hepatic steatosis and renal diseases, and
      is an important disease marker and therapeutic target. Here, we aimed to identify
      the genetic loci for circulating VAP-1 levels. MATERIALS AND METHODS: We carried
      out a genomic-wide linkage scan for the quantitative trait locus of circulating
      VAP-1 levels in 1,100 Han Chinese individuals from 398 families in the Stanford
      Asian Pacific Program for Hypertension and Insulin Resistance study. Regional
      association fine mapping was carried out using additional single-nucleotide
      polymorphisms. RESULTS: The estimated heritability of circulating VAP-1 levels is
      high (h2 = 69%). The most significant quantitative trait locus for circulating
      VAP-1 was located at 38 cM on chromosome 20, with a maximum empirical logarithm
      of odds score of 4.11 (P = 6.86 * 10-6 ) in females. Regional single-nucleotide
      polymorphism fine mapping within a 1-unit support region showed the strongest
      association signals in the MACRO domain containing 2 (MACROD2) gene in females (P
      = 5.38 * 10-6 ). Knockdown of MACROD2 significantly suppressed VAP-1 expression
      in human adipocytes, as well as the expression of key adipogenic genes.
      Furthermore, MACROD2 expression was found to be positively associated with VAP-1
      in human visceral adipose tissue. CONCLUSION: MACROD2 is a potential genetic
      determinant of serum VAP-1 levels, probably through transcriptional regulation of
      adipogenesis.

PMID- 29364585
TI  - What have we learnt from "real world" data, observational studies and meta
      analyses.
AB  - The incretin therapies glucagon-like peptide-1 receptor agonists (GLP-1 RA) and
      dipeptidyl peptidase-IV (DPP-IV) inhibitors are now well-established as second
      and third-line therapies and in combination with insulin for the treatment of
      type 2 diabetes. Over the last decade, there is accumulating evidence of their
      efficacy and safety from both large multicentre randomized clinical trials (RCT)
      and observational studies. Cardiovascular outcome trials have confirmed that
      several of these agents are also non-inferior to placebo with the GLP-1 RA
      liraglutide and semaglutide recently found to be superior in terms of major
      adverse cardiovascular events. Observational studies and post-marketing
      surveillance provide real world evidence of safety and effectiveness of these
      agents and have provided reassurance that signals for pancreatitis and pancreatic
      cancer seen in clinical trials are not of major concern in large patient
      populations. Well-designed real world studies complement RCTs and systematic
      reviews but appropriate data and methodologies, which are constantly improving,
      are necessary to answer appropriate clinical questions relating to the use of
      incretin therapies.

PMID- 29364586
TI  - A review of GLP-1 receptor agonists: Evolution and advancement, through the lens
      of randomised controlled trials.
AB  - AIMS: To review the evolution and advancement of GLP-1 receptor agonist (GLP-1RA)
      therapy, through the lens of randomised controlled trials, from differentiating
      characteristics, efficacy, safety, tolerability, and cardiovascular outcomes, to
      evidence gaps and next steps. METHODS: Clinical review of published phase 3 or
      later RCT data studying efficacy, safety, and outcomes of approved GLP-1 RA
      therapies. RESULTS: Through a wealth of studies, including both placebo
      controlled and active-controlled studies, GLP-1 RAs have demonstrated high
      glycemic efficacy and ability to facilitate weight loss, with minimal risk of
      hypoglycemia, potential to restore beta cell function, and evidence for improved
      cardiovascular outcomes in those at risk. CONCLUSIONS: Over a decade of clinical
      studies have established the unique contributions of GLP-1 RAs in the treatment
      of diabetes. Individual differences between the different GLP-1 RAs, in delivery,
      pharmacokinetic and clinical effects, exist, allowing for tailored approaches to
      clinical care. The strength of evidence generated through RCTs, both short-term
      and long-term studies, will continue to evolve and inform our current paradigms
      in diabetes care.

PMID- 29364587
TI  - Efficacy of glucagon-like peptide-1 receptor agonists compared to dipeptidyl
      peptidase-4 inhibitors for the management of type 2 diabetes: A meta-analysis of
      randomized clinical trials.
AB  - AIMS: Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4)
      inhibitors are both incretin-based therapies for type 2 diabetes (T2DM) but have
      distinct efficacy and side effect profiles. We thus performed a systematic review
      and meta-analysis to compare the effects of GLP-1 agonists to DPP-4 inhibitors on
      glycaemic control, weight and incidence of adverse events in adults with T2DM. We
      also sought to determine whether there was any additional effect in switching
      from DPP-4 inhibitor to GLP-1 agonist. MATERIALS AND METHODS: We systematically
      searched PubMed, Embase and ClinicalTrials.gov for (1) randomized controlled
      trials (RCTs) comparing any GLP-1 agonist to any DPP-4 inhibitor and (2)
      interventional studies where a DPP-4 inhibitor was switched to a GLP-1 agonist.
      We assessed pooled data using random-effects model (CRD42017057115). RESULTS: The
      pooled analysis of 13 RCTs (n = 4330) showed that, compared to DPP-4 inhibitors,
      GLP-1 agonists yielded a greater mean reduction in glycated haemoglobin (HbA1c)
      of -0.41% (95% CI -0.53 to -0.30) and in weight of -2.15 kg (-3.04 to -1.27). GLP
      1 agonists were associated with greater likelihood of gastrointestinal side
      effects with no increased risk of hypoglycaemia. In 5 interventional studies (n =
      433), switching from DPP-4 inhibitor to GLP-1 agonist yielded further mean
      reduction in HbA1c of -0.69% (-1.03 to -0.35) and in weight of -2.25 kg (-3.12 to
      -1.38). CONCLUSIONS: GLP-1 agonists yield greater reduction in HbA1c and weight
      as compared to DPP-4 inhibitors, with increased incidence of gastrointestinal
      symptoms but not hypoglycaemia. Replacing a DPP-4 inhibitor with GLP-1 agonist
      provides additional benefits in glycaemic control and weight loss.

PMID- 29364588
TI  - Incretin hormones: Their role in health and disease.
AB  - Incretin hormones are gut peptides that are secreted after nutrient intake and
      stimulate insulin secretion together with hyperglycaemia. GIP (glucose-dependent
      insulinotropic polypeptide) und GLP-1 (glucagon-like peptide-1) are the known
      incretin hormones from the upper (GIP, K cells) and lower (GLP-1, L cells) gut.
      Together, they are responsible for the incretin effect: a two- to three-fold
      higher insulin secretory response to oral as compared to intravenous glucose
      administration. In subjects with type 2 diabetes, this incretin effect is
      diminished or no longer present. This is the consequence of a substantially
      reduced effectiveness of GIP on the diabetic endocrine pancreas, and of the
      negligible physiological role of GLP-1 in mediating the incretin effect even in
      healthy subjects. However, the insulinotropic and glucagonostatic effects of GLP
      1 are preserved in subjects with type 2 diabetes to the degree that
      pharmacological stimulation of GLP-1 receptors significantly reduces plasma
      glucose and improves glycaemic control. Thus, it has become a parent compound of
      incretin-based glucose-lowering medications (GLP-1 receptor agonists and
      inhibitors of dipeptidyl peptidase-4 or DPP-4). GLP-1, in addition, has multiple
      effects on various organ systems. Most relevant are a reduction in appetite and
      food intake, leading to weight loss in the long term. Since GLP-1 secretion from
      the gut seems to be impaired in obese subjects, this may even indicate a role in
      the pathophysiology of obesity. Along these lines, an increased secretion of GLP
      1 induced by delivering nutrients to lower parts of the small intestines (rich in
      L cells) may be one factor (among others like peptide YY) explaining weight loss
      and improvements in glycaemic control after bariatric surgery (e.g., Roux-en-Y
      gastric bypass). GIP and GLP-1, originally characterized as incretin hormones,
      have additional effects in adipose cells, bone, and the cardiovascular system.
      Especially, the latter have received attention based on recent findings that GLP
      1 receptor agonists such as liraglutide reduce cardiovascular events and prolong
      life in high-risk patients with type 2 diabetes. Thus, incretin hormones have an
      important role physiologically, namely they are involved in the pathophysiology
      of obesity and type 2 diabetes, and they have therapeutic potential that can be
      traced to well-characterized physiological effects.

PMID- 29364589
TI  - The novel HLA-DQB1*03:01:01:12 allele, identified by next-generation sequencing
      in a Chinese family.
AB  - DQB1*03:01:01:12 differs from DQB1*03:01:01:01 at nucleotide 2016 (G > T), 3495
      (G > A), 3897 (G > A), and 6909 (T > C).

PMID- 29364590
TI  - Next-generation sequencing-based typing of a new allele HLA-DQB1*03:01:01:20 in a
      Chinese family.
AB  - DQB1*03:01:01:20 showed one nucleotide difference when compared to
      DQB1*03:01:01:01 at 224 (C>T).

PMID- 29364591
TI  - Total Synthesis of Astellatol.
AB  - A nearly-30-year-old unanswered synthetic puzzle, astellatol, has been solved in
      an enantiospecific manner. The highly congested pentacyclic skeleton of this rare
      sesterterpenoid, which possesses a unique bicyclo[4.1.1]octane motif, ten
      stereocenters, a cyclobutane that contains two quaternary centers, an exo
      methylene group, and a sterically encumbered isopropyl trans-hydrindane motif,
      makes astellatol arguably one of the most challenging targets for sesterterpenoid
      synthesis. An intramolecular Pauson-Khand reaction was exploited to construct the
      right-hand side scaffold of this sesterterpenoid. An unprecedented reductive
      radical 1,6-addition, mediated by SmI2 , forged the cyclobutane motif. Last, a
      strategic oxidation/reduction step provided not only the decisive solution for
      the remarkably challenging late-stage transformations, but also a highly valuable
      unravelling of the notorious issue of trans-hydrindane synthesis. Importantly,
      the synthesis of astellatol showcases a rapid, scalable strategy to access
      diverse complex isopropyl trans-hydrindane sesterterpenoids.

PMID- 29364592
TI  - Live nondirected uterus donors: Psychological characteristics and motivation for
      donation.
AB  - Emerging research suggests that uterus transplantation is a viable option for
      women without a uterus who want to become pregnant and carry a child to term.
      Currently, no knowledge exists regarding nondirected uterus donors. This study
      (NCT 02656550) explored the baseline psychological characteristics of nondirected
      uterus donors at a single study site. Of the 62 potential donors who underwent
      initial screening, 6 nondirected donors were chosen and participated in uterus
      donation. Participants received a comprehensive evaluation, which included
      clinical history and psychological assessments. The mean age of the donors was 42
      years; most (83%) were white/not Hispanic, and all had a college degree. Current
      depression was reported by 2 participants, past depression was reported in 2
      participants, and past anxiety was reported in 3 participants. Based on several
      different psychological measures, donors had a higher general well-being than the
      normative sample, and none of the participants' scores indicated psychological
      distress. All 6 women indicated that giving another woman an opportunity to carry
      her own child was a motivation for pursuing uterus donation. Further research on
      potential psychological motives and gains for the donor as well as long-term
      effects on donors is crucial for ethical practice.

PMID- 29364593
TI  - Standard abbreviations.

PMID- 29364594
TI  - Biosimilars in Dermatology - theory becomes reality.
AB  - Biosimilars are biological medicines that are analogues of a specific reference
      product. Biosimilars of the tumor necrosis factor alpha inhibitors infliximab and
      etanercept are already approved and available for dermatological indications.
      Regulatory agencies require in-depth analysis of physicochemical and functional
      properties of these highly complex molecules as well as clinical data on their
      similarity regarding efficacy and safety in at least one clinical trial in a
      sensitive and homogeneous population. Thus, it must be shown that biosimilars are
      essentially the same as the originator product if they are to be licensed in
      regulated drug markets. As a consequence, these data are extrapolated from one
      molecule (the originator) to another (biosimilar) resulting in an approval that
      includes the same indications as the originator product. While extrapolation is
      well accepted and regulated, clear recommendations regarding the
      interchangeability of originators and biosimilars as well as data on multiple
      consecutive switching are missing. Current scientific knowledge does not argue
      against the use of biosimilars for dermatological indications, but sequential
      switching of biosimilars should be considered carefully. To increase confidence
      and enhance evidence for biosimilars, accurate documentation of the specific
      products given to each patient is essential and should preferably be included in
      patient registries.

PMID- 29364595
TI  - Microphysiological Analytic Platforms (MAPs): Precision Organs on Chip.

PMID- 29364596
TI  - An Accessible Organotypic Microvessel Model Using iPSC-Derived Endothelium.
AB  - While organotypic approaches promise increased relevance through the inclusion of
      increased complexity (e.g., 3D extracellular microenvironment, structure/function
      relationships, presence of multiple cell types), cell source is often overlooked.
      Induced pluripotent stem cell (iPSC)-derived cells are potentially more
      physiologically relevant than cell lines, while also being less variable than
      primary cells, and recent advances have made them commercially available at costs
      similar to cell lines. Here, the use of induced pluripotent stem cell-derived
      endothelium for the generation of a functional microvessel model is demonstrated.
      High precision structural and microenvironmental control afforded by the design
      approach synergizes with the advantages of iPSC to produce microvessels for
      modeling endothelial biology in vitro. iPSC microvessels show endothelial
      characteristics, exhibit barrier function, secrete angiogenic and inflammatory
      mediators, and respond to changes in the extracellular microenvironment by
      altering vessel phenotype. Importantly, when deployed in the investigation of
      neutrophils during innate immune recruitment, the presence of the iPSC
      endothelial vessel facilitates neutrophil extravasation and migration toward a
      chemotactic source. Relevant cell sources, such as iPSC, combine with organotypic
      models to open the way for improved and increasingly accessible in vitro tissue,
      disease, and patient-specific models.

PMID- 29364597
TI  - Formation of a Subunit Form of the Core Light-Harvesting Complex from Sulfur
      Purple Bacteria Ectothiorhodospira haloalkaliphila with Different Carotenoid
      Composition.
AB  - B820 subunits from a purple sulfur bacterium Ectothiorhodospira. haloalkaliphila
      strain ATCC 51935T were obtained by treatment of Carotenoid free LH I-RC
      complexes of this bacterium with P--octylglu- copyranoside (beta-OG). The same
      complexes with 100% carotenoid content were unable to dissociate to B820
      subunits, but disintegrated to monomeric bacteriochlorophyll (BChl) regardless of
      their carotenoid compo- sition. The degree of dissociation of the LH 1-RC
      complexes with an intermediate content of carotenoids (the' B820 formation) was
      directly dependent on the quantity of carotenoids in the samples. The resulting
      B820 subunits did not contain carotenoids. B820 subunits easily aggregated to
      form a complex with an absorption . peak at 880 nm at decreased beta-OG
      concentration. Analysis of the spectra of the LH I-RC complexes isolated from the
      cells with different'levels of carotenogenesis inhibition led to the conclusion
      of the heterogeneity of the samples with a predominance in them of (a) the
      fraction with 100% of carotenoids and (b) the fraction of carotenoid free
      complexes.

PMID- 29364598
TI  - Emended Description of Methylovorus glucosotrophus Govorukhina and Trotsenko
      1991.
AB  - Phylogeneticanalysis based,on comparison of the 16S rRNA gene sequences in
      combination with comparative analysis of physiological, biochemical, and
      chemotaxonomic characteristics and DNA-DNA hybridization revealed that
      "Methylobacillusfructoseoxidans" 34 (VKM B-1609 = DSM 5897 and-Methylov- orus
      glucosotrophus 6B 1T (ATCC 49758T = DSM 6874T = VKM B- 1745T = NCIMB 13222 )
      belong to the same Methylovorus species. Extended description of the limited
      facultative methylotroph Methylovorus gluco- sotrophus is proposed, which
      includes the fructose-utilizing strain 34. Emended description of Methylovorus
      glucosotrophus is provided.

PMID- 29364599
TI  - Structure and Seasonal Trophodynamics of Picophytoplankton in Sevastopol Bay and
      Adjacent Waters (the Black Sea).
AB  - Abundance and seasonal trophodynamics. (specific growth rate, daily production,
      and grazing mortality) of the major picophytoplankton components, Synechococcus
      cyanobacteria (Syn) and picoeukary- otes (Pico-E), were studied at three stations
      in Sevastopol Bay and adjacent coastal waters (the Black Sea) in 2014 by flow
      cytometry and the dilution method. Pico- E abundance was shown to increase along
      the nutrient and pollution gradient from the coastal waters outside the bay
      (annual average of 7.3 +/- 5.4 x 103 cells mL-1) to the eastern corner of the bay
      (28.7 +/- 11.4 x 103 cells mL-1), while no relation was found between the water
      pollution status.and Syn abundance (9.9 +/- 8.7 x 103 cells mL-1, at all the
      stations, n=27). Matter flows through the communities (daily production for Syn
      and Pico-E 0-16.6 and 0-19.3 MUg C L- day-1, respec- tively; grazing mortality
      for Syn and PicoE 0-3.6 and 0-21.2 MUg C L-1 day-1, respectively) were comparable
      to or even exceeded their biomass stocks (<0.05-6.8 and 0.9-26.5 MUg C L- for Syn
      and PicoE, respectively), indicating high biomass turnover rates. The highest
      flow-to-stock ratio (up to 6 for Syn) and,a significant imbalance between daily
      production (P) and grazing mortality (G) were observed in the most polluted and
      eu- trophicated waters of the bay in spring (Pico-E: P/G <.1) and late summer
      (Syn: P/G > 1). Black River inflow to the bay was hypothesized to be among the
      mechanisms maintaining.this pronounced and long-term im- balance in the open
      system without any negative consequences for the picophytoplankton assemlages.

PMID- 29364600
TI  - Microbial Community Associated with Thioploca sp. Sheaths in the Area of the
      Posolski Bank Methane Seep, Southern Baikal.
AB  - Bacterial mats formed by a colorless sulfur bacterium Thioploca sp. in the area
      of the Posolski Bank cold methane seep (southern Baikal) were -studied using
      electron microscopy and phylogenetic analysis. Morphologically the bacteria were
      identified as Thioploca ingrica.- Confocal microscopy of DAPI-stained samples
      revealed numerous rod-shaped, filamentous, and spiral microorganisms in the
      sheaths, as well as in- side and between the trichomes. Transmission electron
      microscopy revealed nonvacuolated bacteria and small cells-without cell envelopes
      within the sheath. Bacteria with pronounced intracytoplasmic membranes
      characteristic; of type I methanotrophs were observed at the outer side of the
      sheath. Based on analysis of the 16S rRNA gene sequences, the following phyla
      were idenified in the sheath community: Bacteroidetes, Nitro- spira, Chloroflexi,
      Planctomycetes, Verrucomicrobia,'y-, and 6-Proteobacteria, Euryarchaeota,
      Crenarchaeota, and Thaumarchaeota, as well as anammox bacteria. A hypothetical
      scheme of matter flows in the Lake Baikal bacterial mats was proposed based on
      the data on metabolism of the cultured homologues.

PMID- 29364601
TI  - Succession Processes in the Anoxygenic Phototrophic Bacterial Community in Lake
      Kislo-Sladkoe (Kandalaksha Bay, White Sea).
AB  - The community of anoxygenic phototrophic bacteria (APB) in the water column of
      Lake Kislo- Sladkoe (Kandalaksha Bay, White Sea), which has recently become
      separated from the sea, was investigated in March-April 2012, March-April 2013,
      and in September 2013. The lake, which was previously considered meromictic, was
      in fact mixed and was strongly affected by the sea. In winter the lake is
      sometimes washed off with seawater, and this together with the seasonal cycles of
      succession processes determines the succession of the community. The consequences
      of the mixing in autumn 2011 could be observed in the APB community as late as
      autumn 2013. Green-colored green sulfur bacteria (GSB) usually predominated in
      the chemocline. In winter 2013 stagnation resulted in turbidity of water under
      the ice, which was responsible for both predom- inance of the brown GS B forms
      and the changes ratio of the species of purple sulfur bacteria (PS B) in anoxic
      water layers. Production of anoxygenic photosynthesis in the lake was at least
      240 mg C m-2 day-- in September and 0-20 mg C m-2 day- in March-April, which
      corresponded to 40 and 69%, respectively, of oxygenic photosynthesis. Okenone
      containing purple sulfur bacteria, strain TcakPS12 were isolated in 2012 from
      lake water. The ells of this strain form filaments of not separated cells. Strain
      TcakPS12 exhibited 98% similarity with the type strains of Thiocapsapendens
      DSM.236 and Thiocapsa bogorovii BBS, as well as with the strains AmPS10 and
      TcyrPS 10, which were isolated from Lake Kislo-Sladkoe in 2010.

PMID- 29364602
TI  - Microbial Community Composition and Methanotroph Diversity of a Subarctic Wetland
      in Russia.
AB  - This study assessed the microbial diversity, activity, and composition of methane
      oxidizing communities of a subarctic wetland in Russia,with mosaic cover of
      Sphagnum mosses and lichens of the genera Cladonia and Cetraria. Potential
      methane-oxidizing activity of peat sampled from lichen-dominated wetland sites
      was higher than that in the sites dominated by Sphagnum mosses. In peat from
      lichendominated sites, major bacterial groups identified by high-throughput
      sequencing of the 16S rRNA genes were the Acidobacteria (35.4-41.2% of total 16S
      rRNA gene reads), Alphaproteobacteria (19.1-24.2%), Gammaproteobacteria (7.9
      11.1%), Actinobacteria (5.5-13.2%), Planctomycetes (7.2-9.5%), and
      Verrucomicrobia (5.1-9.5%). The distinctive feature of this community was high
      proportion of Subdivision 2 Acidobacteria, which are not char- acteristic for
      boreal Sphagnum peat bogs. Methanotrophic community composition was determined by
      mo- lecular analysis of the pmoA gene encoding particulate methane monooxygenase.
      Most (-80%) of all pmoA gene fragments revealed in peat from lichen-dominated
      sites belonged to the phylogenetic lineage represented by a microaerobic spiral
      shaped methanotroph, "Candidatus Methylospira mobilis." Members of the genus
      Methylocystis, which are typical inhabitants of boreal Sphagnum peat bogs,
      represented only a minor group of indigenous methanotrophs. The specific feature
      of a methanotrophic community in peat from lichen-dominated sites was the
      presence of uncultivated USCa (Upland Soil Cluster alpha) methanotrophs, which
      are typical for acidic upland soils showing atmospheric methane oxidation. The
      methanotrophic community composition in lichen-dominated sites of a tundra
      wetland, therefore, was markedly different from that in bo- real Sphagnum peat
      bogs.

PMID- 29364603
TI  - Phylogenetic and Functional Prokaryotic Diversity in the Hoito-Gol Mesothermal
      Mineral Spring (Eastern Savan Mountains. Buryat Renuhlie).
AB  - High-throughput sequencing was used for comparative analysis of microbial
      communities of the water and mat from the Hoito-Gol mesothermal mineral sulfide
      spring (Eastern Sayan Mountains, Buryat Republic). Activity of microbial
      communities was determined. While both spring biotopes were dominated by members
      of three bacterial phyla, Proteobacteria, Bacteroidetes, and Firmicutes, they
      differed drastically in the composition of predominant phylotypes (at the genus
      level). In the water, the organisms wide spread in aquatic'environments were
      predominant, mostly aerobic chemoorganotrophs of the generaAcinetobacter, Pe-
      dobacter, and Flavobacterium. In the microbial mat,;the organisms actively
      involved in the sulfur cycle predominated, including sulfur-reducing bacteria
      Sulfurospirillum, sulfate-reducing deltaproteobacteria, sulfur- oxidizing
      chemoautotrophic bacteria, anoxygenic phototrophic bacteria of,the phyla
      Chloroflexi and Chloro- bi, as well as purple bacteria belonging to the Q-, P--,
      and y-Proteobacteria. Microbial mats of the spring exhibited higher phylogenetic
      diversity compared to high-temperature mats containing photosynthetic
      microorganisms.

PMID- 29364604
TI  - [Diversity and Physiological and Biochemical Properties of Heterotrophic
      Bacteria. Isolated from Lake Baikal Neuston.]
AB  - For heterotrophic microorganisms (44 strains) isolated-from the surface film of
      Lake Baikal, iden- tification was carried out and their. physiological and
      biochemical characteristics were determined. Com- pared to the water column,
      diversity of cultured heterotrophs was low, indicating formation of stable micro-
      bial communities at the air-water interphase interface. Heterotrophic bacteria
      isolated from the surface mi- crolayer exhibited the enzymatic activity
      comparable to that for strains form other biofilm associations. Deinococcusfi6us
      strain NA202 'vas the most active component of the community, capable of
      utilization of the broadest spectrum of mono- and disaccharides,'sugars, and
      amino acids. This strain possessed the highest diversity of extracellular enzymes
      and was the most resistant to UV radiation. The physiological and bio- chemical
      properties of this strain may-be responsible for its adaptation to survival in
      extreme conditions of the surface microlayer. Our results improve our
      understanding of occurrence of UV-resistant strains in freshwater ecosystems.

PMID- 29364605
TI  - [Modeling the Propagation of Microbial Cells and Phage Particles from the Sites
      of Permafrost Thawing.]
AB  - A method is proposed for integral assessment of the propagation of microbial
      cells and viral parti- cles during seasonal thawing of relic ice wedge layers.
      The results of on-site and laboratory investigation car- ried out in the upper
      part of permafrost exposure at Mamontova Gora (Yakutiya, Russia) are presented.
      To increase reliability of the results, suspensions of two microbial species and
      two coliphage species were intro- duced as biomarkers directly on the surface of
      thaing ice and in the meltwater flow. Each of the four different model biological
      objects was shown to possess unique parameters of movement in the meltwater flow
      and is able to move 132 m in 25-35 min with the water flow.

PMID- 29364606
TI  - [Relations between Bacterioplankton, Heterotrophic Nanoflagellates, and
      Virioplankton in the Littoral Zone of a LarRe Plain Reservoir:. ImDact of Bird
      Colonies.]
AB  - Interactions of the main components of microbial planktonic food web (bacteria,
      heterotrophic nanoflagellates, and viruses) were studied in a protected overgrown
      littoral zone of the Rybinsk Reservoir (Upper Volga).. The effect of bird
      colonial, settlements (the Laridae family) on these processes was deter- mined.
      The following systems exhibited significant negative correlations: "heterotrophic
      nanoflagellates- large rod-shaped bacteria" ("predator-prey"), "viruses
      bacteriophages-bacterial products" ("parasite-. host") and "heterotrophic
      nanoflagellates-viruses-bacteriophages." Relations between biotic factors con-
      trolling bacterial development were more pronounced outside the zone affected by
      colonial bird settlements. Near the bird colony the role of viruses in mortality
      of planktonic bacteria increased. Reproduction of bacte- rial cells accelerated
      in response to the increase in feeding activity of heterotrophic nanoflagellates.
      Viruses- bacteriophages and heterotrophic nanoflagellates probably eliminate
      different targets until medium-sized cells become predominant in the bacterial
      community. Then heterotrophic nanoflagellates consume bacterial cells infected
      with viruses.

PMID- 29364607
TI  - [Role of the Microbial Community in Formation of Speleothem (Moonmilk) in the
      Snezhnaya Carst Cave (Abkhazia).]
AB  - The resi Its of investigation of speleothem (moonmilk) from the Snezhnaya cave
      (West Caucasus, Abkhazia) are-reported. The structure of microbial complexes from
      moonmilk was investigated by quantita- tive PCR; strains of culturable
      microorganisms were isolated and their preferred temperature and carbon sources
      were determined. Among eubacteria, -34% belonged to the iron bacteria
      (Rhodoferax). Most bacte- rial strains were shown to be facultative psychrophiles
      with the maximum growth rate at 4C. The microstruc- ture and elemental
      composition of mionmilk were investigated using a scanning electron microscope
      (EVO- 40HV, Carl Zeiss) and silicon drifi X-ay detector X-MAX 80 ffM2' The
      visually plastic and homogeneous mass of moonmilk was shown to be highly
      heterogeneous, containing various microstructures. The elemental composition of
      some nanostructures depended on the structure of bacterial biofilms. Some loci of
      the biofilm were found to contain up to 46% (wt/wt) of iron oxides. Calcium
      content was high, up to 61.5% (wt/wt) only in cubic crystalline structures which
      were not involved in microbiological processes.

PMID- 29364608
TI  - [Not Available.]

PMID- 29364609
TI  - [Not Available.]

PMID- 29364610
TI  - Development of Dual Neurotrophins-Encapsulated Electrosupun Nanofibrous Scaffolds
      for Peripheral Nerve Regeneration.
AB  - Nerve growth factor (NGF) is widely used for repairing peripheral nerve injury
      because of its capability in dominating the survival, migration, proliferation,
      and differentiation of nerve cells. Monosialoganglioside (GM1), as another kind
      of nerve growth factor, works for regulating NGF function. In this study, GM1 and
      NGF were incorporated into the Poly(l-lactic acid-co-epsilon-caprolactone)/silk
      fibroin (PLCL/SF) nanofibers by the coaxial electrospinning. The fibers
      morphology and core-shell structure were characterized by SEM and TEM. The
      scaffolds demonstrated high tensile stress with good flexibility. In vitro cell
      viability studies indicated that the scaffolds incorporating both GM1 and NGF
      played a synergistic effect to enhance Schwann cells (SCs) proliferation and
      Pheochromocytoma (PC12) cells differentiation, in comparison to the scaffolds
      only incorporating NGF. Subsequently, the nanofibrous conduit scaffolds (NCSs)
      were evaluated in vivo in a rabbit sciatic nerve defect model. The NGF/GM1
      incorporated NCSs group performed better nerve function recovery than single
      incorporated group, in consideration of the compound muscle action potential
      (CMAP) and nerve conduction velocity (NCV) results. Furthermore, hematoxylin and
      eosin (H&E) staining, toluidine blue (TB) staining, and transmission electron
      microscope (TEM) analysis displayed better nerve regeneration of NGF/GM1
      incorporated NCSs both quantitatively and qualitatively. Therefore, the results
      indicated the dual neurotrophins-incorporated NCSs had potentials for the
      application in peripheral nerve repairing.

PMID- 29364611
TI  - [Adipose tissue composition in puberty and postpuberty according to age, sex
      (gender), physical activity and alimentary behavior].
AB  - The study involved 110 adolescents from 15 to 22 years (35 boys, 75 girls). To
      assess eating habits and physical activity we used WHO questionnaires. We also
      analyzed anthropometry, bioimpedance data, parameters of the cardiovascular
      system: systolic and diastolic blood pressure, heart rate. It has been shown,
      that body mass index (BMI) in adolescents didn't correlate with the content of
      both total and visceral adipose tissue in the body and shoud not be used as a
      major diagnostic criterion of obesity. An excessive content of total adipose
      tissue was shown in 15% of the puberty and postpuberty teens. Visceral fat
      content was significantly higher in male, than female (3.03+/-3.31 vs 2.11+/
      1.57%), independently of the total fat percentage (18.91+/-16.83 and 31.72+/
      19.24% respectively). The visceral fat in the body begins to increase in age of
      16. According to the authors, such an effect in boys and girls is associated with
      the final changes of puberty (concentration of sex steroids). Such hormons like
      testosterone and progesterone and estradiol have different effects on the white
      adipose tissue and play a key role in proceses of its differentiation and
      metabolism. Percentage of total adipose tissue depends on dietary habits in the
      first place - the predominance of fast food. A significant relationship of
      physical activity and the percentage of visceral fat was shown.

PMID- 29364612
TI  - Renal Epithelial Cell Injury Induced by Calcium Oxalate Monohydrate Depends on
      their Structural Features: Size, Surface, and Crystalline Structure.
AB  - Urinary crystals in normal and kidney stone patients often differ in crystal
      sizes and surface structures, but the effects of different crystal properties on
      renal tubular epithelial cells remain unclear. This study aimed to compare the
      cytotoxicity of micron/nano-calcium oxalate monohydrate (COM) crystals with sizes
      of 50 nm, 200 nm, 1 MUm, 3 MUm, and 10 MUm to African green monkey renal
      epithelial (Vero) cells, to reveal the effect of crystal size and surface
      structure on cell injury, and to investigate the pathological mechanism of
      calcium oxalate kidney stones. Cell viability, cellular biochemical parameters,
      and internalized crystal amount in Vero cells were closely associated with the
      size of COM crystals. At the same concentration (200 MUg/mL), COM-1 MUm induced
      the most serious injury to Vero cells and caused the most significant change to
      cellular biochemical parameters, which were related to the specific porous
      structure and highest internalized amount in Vero cells. By contrast, COM-50 nm
      and COM-200 nm crystals lost their small size effect because of serious
      aggregation and weakened their toxicity to cells. COM-3 MUm and COM-10 MUm
      crystals were too large for cells to completely internalize; these crystals also
      exhibited a low specific surface area and thus weakened their toxicity. The
      excessive expression of intracellular ROS and reduction of the free-radical
      scavenger SOD were the main reasons for cell injury and eventually caused
      necrotic cell death. Crystal size, surface structure, aggregation, and
      internalization amount were closely related to the cytotoxicity of COM crystals.

PMID- 29364613
TI  - [The dependence of diet macronutrient composition and energy intake from human
      phase of the weekly cycle - weekdays/weekends].
AB  - When planning your diet regime is desirable to focus on the natural feeding
      behavior of the person. However, many aspects of eating behavior are not studied.
      The aim of this work was to study the changes of diet calorie and nutrient
      composition depending on the body mass index (BMI), time of day, week cycle
      phase: weekends/weekdays, and the availability of rational installation in
      nutrition. The study involved 67 women aged 29 to 49 years with a BMI of 18.3 to
      34.2 kg/m2. Macronutrient composition and energy value of the diet were evaluated
      by analyzing the food diaries, which were filled by all respondents continuously
      for 8 workdays and 4 weekends. The results of this study showed no significant
      correlation between BMI and calorie intake, while a positive correlation was
      observed between BMI and fat component of the diet (r=0.362, p<=0.05). It was
      also found that the restriction of food intake in the evening (after 8 pm) did
      not lead to a decrease in total daily energy value of the diet, and was
      characterized by the consumption in the evening about 31% of the total fat
      intake. Diet energy value was significantly higher on weekends than during the
      week and was 2376+/-394 against 1940+/-402 kcal (p<0.05). According to the data
      obtained, compliance "restriction of supply in the evening" does not lead to a
      significant reduction in daily caloric intake.

PMID- 29364614
TI  - [Toxicological assessment of nanostructured silica. IV. Immunological and
      allergological indices in animals sensitized with food allergen and final
      discussioin].
AB  - This paper is the final in a series of publications on the assessment of subacute
      oral toxicity of nanostructured silica (SiO2). Preparation studied was a
      commercial nanopowder of SiO2, obtained by hydrolysis of tetrachlorosilane in the
      gaseous phase with the size of primary nanoparticles (NPs) of 5-30 nm. The
      experiment was conducted in 95 male Wistar rats weighing 150-180 g, divided into
      6 groups numbering 25 (group 1), 26 (group 2), 11 (groups 3-6) of animals. The
      aqueous dispersion of SiO2 after sonication was administered to animals of groups
      2, 4 and 6 for 28 days by intragastric gavage at a dose of 100 mg/kg of body
      weight per day. Animals of groups 1, 3, and 5 were treated with deionized water.
      On the 1st, 3d, 5th and 21st day of experiment the rats of groups 1, 2, 3 and 4
      were sensitized intraperitoneally with hen's egg ovalbumin (OVA) adsorbed to
      aluminum hydroxide. Intravenous administration of the challenge dose OVA to rats
      in groups 1 and 2 was carried out on the 29th day. In the same period animals of
      groups 3-6 were bled for analysis of cellular immunity. There were evaluated the
      severity of systemic anaphylaxis reaction, the level of specific IgG antibodies
      to OVA in sensitized animals, state of erythrocytes, platelets and leukocytes of
      peripheral blood using standard methods. Using flow cytometry there were measured
      contents of lymphocyte populations of B-lymphocytes (CD45RA+), total T
      lymphocytes (CD3+), T-helper cells (CD4+), T-cytotoxic cells (CD8+), NKcells
      (CD161a+), phagocytic activity of polymorphonuclear leukocytes in respect of
      latex particles. Serum levels of TNFalpha and IL-10 cytokines were determined by
      ELISA. The result showed that NPs SiO2, at dose of 100 mg/kg body weight had no
      any marked effect on severity of active anaphylactic shock and level of specific
      antibodies. The changes in cellular immunity under the influence of nanomaterial
      had similar direction in sensitized and non-sensitized animals and were more
      pronounced in the latter. Based on the discussion of the results, together with
      data from previous publications it was concluded that oral maximum level without
      observable adverse effect (NOAEL) of nanostructured SiO2 is located below 100
      mg/kg body weight.

PMID- 29364615
TI  - [Rroblems of ensuring the safety of deep-fried fast food products].
AB  - There are no doubts that fast-food restaurants, where deep-frying is actively
      used, are now very popular in Russia. This article focuses on the problems of
      deep-fried food safety. During deep-frying a considerable amount of fat
      penetrates the food. That is why the safety of deep-fried food depends on the fat
      safety and quality, on the level of fat absorption, and on the intensity of
      oxidative changes of fat during storage. This article contains the results of the
      research, which demonstrate that in order to insure the safety of fast-food
      products it is necessary to introduce into normative and technical documents the
      following standards: peroxide value, acid value, content of oxidation products
      insoluble in petroleum ether, and content of epoxides in fat phase and to food
      mass. According to the current norms on content of oxidation products in deep
      frying fat and allowed level of fat absorption by a food product equal to 20%,
      the recommended level of oxidation products insoluble in petroleum ether for
      French fries is not higher than 0.2% to the food mass. As a temporary measure we
      can recommend the level of epoxides not higher than 5 mmol/kg to the food mass.
      It is important to control the content of trans-isomers in deepfrying fat, it
      must be not higher than 2% of fatty acid mass. In order to lower fat absorption
      during French fries production it is recommended to use halffinished products of
      high readiness, and to air fry.

PMID- 29364616
TI  - A Promising Approach for Improving the Coating Stability and In Vivo Performance
      of Biodegradable Polymer-Coated Sirolimus-Eluting Stent.
AB  - Several developments are in progress for improving the performance of drug
      eluting stents (DESs) including use of biodegradable polymers, polymer-free DES,
      fully bioabsorbable stents, and so on. The commercially available DESs still
      suffer from polymer defects that could affect the performance of a DES through a
      series of adverse events such as coating delamination and/or peeling-off that
      lead to non-uniform local drug distribution, restenosis, and thrombosis. The goal
      of this work was to enhance the stability of drug-in-polymer matrix coating on a
      stent metal surface through surface modification. The cobalt-chromium (Co-Cr)
      surface was chemically modified using poly(dopamine) (PDA) nano-coating and
      poly(L-lactide) (PLLA) nano-brush in order to be applied to a biodegradable
      polymer-coated DES. The biodegradable polymer loaded with sirolimus was coated
      using an ultrasonic spray coating instrument. The coating morphology on all
      samples showed a very smooth and uniform coating. The stability of the coating
      was evaluated for 2 months under the circulation system in which the drug-in
      polymer coating on the PLLA brush-modified stent presented the most stable
      coating behavior as compared to other samples. The in vitro sirolimus release
      study from both unmodified and modified stents was studied in phosphate-buffered
      saline (PBS), and the modified stents showed slower sirolimus release profile as
      compared to unmodified stents. In vivo study was performed in a porcine coronary
      artery injury model for 28 days. The percentage of in-stent restenosis area (ISR)
      for PLLA brush-modified sirolimus-eluting stent (SES) decreased significantly as
      compared to unmodified SES and bare metal stent (BMS). This study demonstrated
      that the modification of stent surface using PLLA brushes affects in vitro and in
      vivo performance effectively to be applied for biodegradable polymercoated DES.

PMID- 29364617
TI  - Mineralized Collagen Regulates Macrophage Polarization During Bone Regeneration.
AB  - The host immune response to bone biomaterials is vital in determining the fate of
      scaffolds and also the outcomes of bone regeneration. Mineralized collagen is an
      ideal tissue-engineering scaffold for bone repair; however, little is known about
      its immunomodulatory properties after implantation. In this study,
      extrafibrillarly-mineralized collagen (EMC) and intrafibrillarly-mineralized
      collagen (IMC) scaffolds with different nanostructures were fabricated and their
      immunomodulatory properties via macrophage polarization during bone regeneration
      were investigated. Micro-CT findings showed that the IMC scaffold yielded more
      new bone formation than the EMC scaffold. In the defect area, more CD68 + CD163 +
      M2-like macrophages were observed in the IMC group, while M1-like macrophages
      positive for CD68 and inducible nitric oxide synthase (iNOS) increased
      dramatically in the EMC group. We further demonstrated, from the protein and RNA
      levels, that M2-associated anti-inflammatory cytokines interleukin (IL)-10 and
      arginase-1 were highly expressed in the macrophages seeded on the IMC scaffold,
      while those seeded on the EMC scaffold expressed more M1-related genes iNOS and
      IL-6. Moreover, the macrophage polarization in response to the nanostructure of
      mineralized collagen scaffolds influenced the osteogenesis of human bone marrow
      stromal cells. These findings suggest that the nanostructure of mineralized
      collagen scaffolds affects macrophage functional polarization during bone
      regeneration. The immunomodulatory properties of biomaterial scaffolds can be a
      dictator of bone regeneration outcomes.

PMID- 29364618
TI  - One-Step Fabrication of AgNPs Embedded Hybrid Dual Nanofibrous Oral Wound
      Dressings.
AB  - In the dental medical field, an infection of opened oral tissues by bacteria give
      rise to serious periodontal disease (PD) after trauma or various oral surgery
      such as third molar extraction, oral implant, and unexpected trauma. However,
      progress for bioactive improvement, a prevention of oral tissue contamination,
      has been currently limitation. Therefore, an innovative research is extremely
      important and needed for immediately inhibition of bacteria. In this study, we
      designed a biocompatible oral wound dressing as co-electrospun nanofiber to
      combine gelatin (GE) and polyurethane (PU) containing silver nanoparticle (AgNPs)
      to enhance antibacterial activity targeting to periodontal bacteria. Prior to an
      electrospinning (ELSP), AgNPs was directly synthesized by silver nitrate with
      capping agent within dimethylformamide (DMF) for use as an ELSP solvent. The
      fabricated products were cross-linked by 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide (EDC) and N-hydroxysuccinimide (NHS) followed by characterized via
      theoretical analysis. In results, AgNPs were not only perfectly synthesized
      without a reduction agent, but also electrospun nanofiber (EN) containing AgNPs
      was well fabricated with the modulation of AgNPs levels. Additionally, the
      presence of AgNPs within the fiber strand was clearly shown. In the antibacterial
      test, the developed oral wound dressing showed excellent antibacterial activity
      as increasing content of the AgNPs. All of tests clearly confirmed that our
      strategy may suggest a useful paradigm as oral wound dressing to prevent of a
      bacterial infection as means to oral wound dressing of gingiva and periodontal
      tissues for obviation of periodontitis.

PMID- 29364622
TI  - Curcumin-Loaded Layered Double Hydroxide Nanoparticles-Induced Autophagy for
      Reducing Glioma Cell Migration and Invasion.
AB  - Glioblastoma is difficult to cure due to the high risks of invasion and
      metastasis. Although curcumin has shown beneficial effects against malignant
      glioma cells, its poor properties have limited its application. The aim of this
      study was to design a nanocarrier for curcumin to exert sufficient anti-migration
      and anti-invasion effects on A172 cells. Curcuminloaded layered double hydroxide
      nanoparticles (Cur/LDH NPs) were synthesized, and the physicochemical properties
      were characterized using transmission electron microscopy (TEM), zeta potential,
      Fourier transform infrared spectrometry (FTIR) and X-ray powder diffraction
      (XRD). Then, Cur/LDH NPs were applied to A172 cells to assess the anti-migration
      and anti-invasion effects, cellular uptake, autophagy activity, and the related
      mechanisms. The prepared Cur/LDH NPs were 119+/-34 nm in size and exhibited a
      drug-loading efficiency of 21.31+/-1.83%. Compared with LDH and Cur alone, the
      Cur/LDH NPs significantly reduced cell migration and invasion when applied at low
      doses (0.1 and 0.5 MUg/ml), and these effects were associated with a down
      regulation of PI3K/AKT/mTOR signaling pathway. The Cur/LDH NPs were easily taken
      up by A172 cells and were mainly located in lysosomes and mitochondria in a time
      dependent manner. Importantly, autophagy, which can be triggered by the
      inhibition of mTOR and by nanomaterials, was detected distinctly in A172 cells
      exposed to Cur/LDH NPs via the autophagic marker LC3A/B. In addition, the
      expression levels of Atg5-Atg12 and LAMP-1 were increased in the Cur/LDH NPs
      groups, and autophagic vacuoles were observed via TEM. Our work suggests that
      autophagy can promote the anti-migration and anti-invasion effects of Cur/LDH NPs
      against glioblastoma.

PMID- 29364623
TI  - Photodynamic Therapy Mediated by Upconversion Nanoparticles to Reduce Glial Scar
      Formation and Promote Hindlimb Functional Recovery After Spinal Cord Injury in
      Rats.
AB  - Glial scar formation is one of the major consequences of spinal cord injury,
      which prevents the regenerated axons passing the injured area and forming
      effective synaptic connection. In this paper, we used photodynamic therapy (PDT),
      which was mediated by the upconversion nanoparticles coated with polyethylene
      glycol (PEG) and photosensitizer (UCNPs-PEGM540), to reduce the glial scar
      formation after spinal cord injury. The in vitro experimental results indicated
      that cultured astrocytes could be killed by using upconversion nanoparticles
      after excitation with near infrared light. By transplanting UCNPs-PEG-M540 into
      the margin area of injured epicenter of spinal cord, the recovery of rat's
      hindlimb function was evaluated in Basso, Beattie, Bresnahan locomotor rating
      scale, respectively. The improvement in microenvironment of the injured spinal
      cord was also evaluated by glial fibrillary acidic protein staining,
      neurofiliment staining, biotinylated dextran amine anterograde tracing and
      western blotting. Our results demonstrated that more regenerative axons of
      corticospinal tract were found to surround and pass through the injured cavity to
      the caudal cord with transplanting UCNPs-PEG-M540 into the injured spinal cord.
      In conclusion, our results strongly suggested that upconversion nanoparticles
      combined with photodynamic therapy can promote functional recovery in rats'
      hindlimbs by reducing the formation of glial scar and promoting remyelination of
      injured axons.

PMID- 29364624
TI  - Nanofibrous Mineralized Electrospun Scaffold as a Substrate for Bone Tissue
      Regeneration.
AB  - Fibrous scaffolds that reconstruct the extracellular matrix (ECM) have been
      utilized for tissue regeneration demonstrated potential for guiding stem cell
      differentiation. Nanofibrous scaffolds fabricated by a unique electrospinning
      method enabled us to create tailored, functional scaffolds on-demand. Several
      patterned electrospun poly(epsilon-caprolactone) (PCL) scaffolds were prepared,
      and then utilized for creating a hybrid composite in which bone-like
      hydroxyapatite (b-HA) was deposited onto the unique electrospun scaffolds. The
      mineral deposits onto the patterned PCL scaffolds was confirmed by scanning
      electron microscope (SEM). When culturing human adipose-derived stem cells (hASC)
      onto the different SBF-treated electrospun PCL scaffolds, it was found that the
      hybrid composite can support hASC differentiated into osteoblasts under
      osteogenic differentiation conditions. Image analysis and alamar blue assay
      indicated a significant increase of hASC adhesion and proliferation on the SBF
      treated PCL scaffolds. Subsequent analysis of osteogenic potential by via gene
      expression analysis and alkaline phosphatase (ALP) activity also demonstrated
      that the SBF-treated electrospun PCL made by the modified electrospinning process
      is more favorable for the osteogenic differentiation hASCs. Additionally, results
      of alizarin red S staining and ALP staining at days 7 and 14 showed improved
      deposition of mineralized matrix on the SBF-treated PCL. Therefore, this study
      indicates that the facile scaffold fabrication method described in this study is
      promising approach to prepare osteoconductive scaffold for bone tissue
      engineering.

PMID- 29364644
TI  - Keeping Track of the Electrons.
AB  - Mechanistic investigation and new reaction development are intertwined. This
      interdependence presents challenges and opportunities in development of all
      transformations, particularly for those that employ base metal catalysts. In
      comparison to precious metal counterparts, these catalysts yield less easily to
      mechanistic analysis. However, base metal catalysts can provide new modes of
      reactivity and opportunities for discovery. In this Commentary, we highlight a
      developing field: nickel-catalyzed stereoselective alkyl cross-coupling
      reactions. While key features of the relevant catalytic cycles remain ambiguous,
      chemical intuition and key mechanistic experiments have provided the stepping
      stones for discovery of stereoselective transformations.

PMID- 29364646
TI  - Design of pH-Responsive Polymer Monolith Based on Cyclodextrin Vesicle for
      Capture and Release of Myoglobin.
AB  - beta-Cyclodextrin vesicles (CDVs) were first introduced into the polymer monolith
      to prepare a pH-responsive adsorption material and used for capture and release
      of a cardiac biomarker, myoglobin (Myo). SH-CDV was decorated with adamantane
      modified SH-octapeptide to enhance the encapsulation and release rates of Myo.
      Afterward, SH-CDV was introduced into the polymer monolith via click reaction to
      produce a pH-responsive monolith. Combining with the mass spectrometry detection,
      the CDV-based pH-responsive monolith was used for the enrichment of Myo
      glycopeptides from the mixture of glycopeptides and nonglycoprotein (bovine serum
      albumin) tryptsin digests reach up to 1:10 000. A limit of detection of 0.1 fmol
      was obtained for Myo glycopeptides in the blood sample, indicating the high
      sensitivity of the method. The prepared CDV-based hybrid monolith demonstrated
      itself to be a promising material for capture of glycoproteins in complex
      samples, which provides an efficient strategy for the identification and
      discovery of biomarkers of acute myocardial infarction.

PMID- 29364647
TI  - Role of Chemical Biology in Tuberculosis Drug Discovery and Diagnosis.
AB  - The use of chemical techniques to study biological systems (often referred to
      currently as chemical biology) has become a powerful tool for both drug discovery
      and the development of novel diagnostic strategies. In tuberculosis, such tools
      have been applied to identifying drug targets from hit compounds, matching high
      throughput screening hits against large numbers of isolated protein targets and
      identifying classes of enzymes with important functions. Metabolites unique to
      mycobacteria have provided important starting points for the development of
      innovative tools. For example, the unique biology of trehalose has provided both
      novel diagnostic strategies as well as probes of in vivo biological processes
      that are difficult to study any other way. Other mycobacterial metabolites are
      potentially valuable starting points and have the potential to illuminate new
      aspects of mycobacterial pathogenesis.

PMID- 29364645
TI  - Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6,
      -7, and -8.
AB  - Zinc is emerging as a widely used and important biological regulatory signal.
      Cellular zinc levels are tightly regulated by a complex array of zinc importers
      and exporters to control processes such as apoptotic cell death. While caspase
      inhibition by zinc has been reported previously, the reported inhibition
      constants were too weak to suggest a critical biological role for zinc-mediated
      inhibition. In this work, we have adopted a method of assessing available zinc.
      This allowed assessment of accurate inhibition constants for apoptotic caspases,
      caspase-3, -6, -7, and -8. Each of these caspases are inhibited by zinc at
      intracellular levels but with widely differing inhibition constants and different
      zinc binding stoichiometries. Caspase-3, -6, and -8 appear to be constitutively
      inhibited by typical zinc levels, and this inhibition must be lifted to allow
      activation. The inhibition constant for caspase-7 (76 nM) is much weaker than for
      the other apoptotic caspases (2.6-6.9 nM) suggesting that caspase-7 is not
      inactivated by normal zinc concentrations but can be inhibited under conditions
      of zinc stress. Caspase-3, -7, and -8 were found to bind three, one, and two
      zincs, respectively. In each of these caspases, zinc was present in the active
      site, in contrast to caspase-6, which binds one zinc allosterically. The most
      notable new mechanism to emerge from this work is for zinc-mediated inhibition of
      caspase-8. Zinc binds caspase-8 directly at the active site and at a second site.
      Zinc binding inhibits formation of the caspase-8 dimer, the activated form of the
      enzyme. Together these findings suggest that zinc plays a critical role in
      regulation of apoptosis by direct inactivation of caspases, in a manner that is
      unique for each caspase.

PMID- 29364648
TI  - Tau-Targeted Multifunctional Nanocomposite for Combinational Therapy of
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) remains an incurable disease and lacks efficient
      diagnostic methods. Most AD treatments have focused on amyloid-beta (Abeta)
      targeted therapy; however, it is time to consider the alternative theranostics
      due to accumulated findings of weak correlation between Abeta deposition and
      cognition, as well as the failures of Phase III clinical trial on Abeta targeted
      therapy. Recent studies have shown that the tau pathway is closely associated
      with clinical development of AD symptoms, which might be a potential therapeutic
      target. We herein construct a methylene blue (MB, a tau aggregation inhibitor)
      loaded nanocomposite (CeNC/IONC/MSN-T807), which not only possesses high binding
      affinity to hyperphosphorylated tau but also inhibits multiple key pathways of
      tau-associated AD pathogenesis. We demonstrate that these nanocomposites can
      relieve the AD symptoms by mitigating mitochondrial oxidative stress, suppressing
      tau hyperphosphorylation, and preventing neuronal death both in vitro and in
      vivo. The memory deficits of AD rats are significantly rescued upon treatment
      with MB loaded CeNC/IONC/MSN-T807. Our results indicate that hyperphosphorylated
      tau-targeted multifunctional nanocomposites could be a promising therapeutic
      candidate for Alzheimer's disease.

PMID- 29364649
TI  - Architectonics: Design of Molecular Architecture for Functional Applications.
AB  - The term architectonics has its roots in the architectural and philosophical (as
      early as 1600s) literature that refers to "the theory of structure" and "the
      structure of theory", respectively. The concept of architectonics has been
      adapted to advance the field of molecular self-assembly and termed as molecular
      architectonics. In essence, the methodology of organizing molecular units in the
      required and controlled configurations to develop advanced functional systems for
      materials and biological applications comprises the field of molecular
      architectonics. This concept of designing noncovalent systems enables to focus on
      different functional aspects of designer molecules for biological and
      nonbiological applications and also strengthens our efforts toward the mastery
      over the art of controlled molecular self-assemblies. Programming complex
      molecular interactions and assemblies for specific functions has been one of the
      most challenging tasks in the modern era. Meticulously ordered molecular
      assemblies can impart remarkable developments in several areas spanning energy,
      health, and environment. For example, the well-defined nano-, micro-, and
      macroarchitectures of functional molecules with specific molecular ordering
      possess potential applications in flexible electronics, photovoltaics, photonic
      crystals, microreactors, sensors, drug delivery, biomedicine, and
      superhydrophobic coatings, among others. The functional molecular architectures
      having unparalleled properties are widely evident in various designs of Nature.
      By drawing inspirations from Nature, intended molecular architectures can be
      designed and developed to harvest various functions, as there is an inexhaustible
      resource and scope. In this Account, we present exquisite designer molecules
      developed by our group and others with an objective to master the art of
      molecular recognition and self-assembly for functional applications. We
      demonstrate the tailor-ability of molecular self-assemblies by employing
      biomolecules like amino acids and nucleobases as auxiliaries. Naphthalenediimide
      (NDI), perylenediimide (PDI), and few other molecular systems serve as functional
      modules. The effects of stereochemistry and minute structural modifications in
      the molecular designs on the supramolecular interactions, and construction of
      self-assembled zero-dimensional (OD), one-dimensional (1D), and two-dimensional
      (2D) nano- and microarchitectures like particles, spheres, cups, bowls, fibers,
      belts, helical belts, supercoiled helices, sheets, fractals, and honeycomb-like
      arrays are discussed in extensive detail. Additionally, we present molecular
      systems that showcase the elegant designs of coassembly, templated assembly,
      hierarchical assembly, transient self-assembly, chiral denaturation, retentive
      helical memory, self-replication, supramolecular regulation, supramolecular
      speciation, supernon linearity, dynamic pathway complexity, supramolecular
      heterojunction, living supramolecular polymerization, and molecular machines.
      Finally, we describe the molecular engineering principles learnt over the years
      that have led to several applications, namely, organic electronics, self
      cleaning, high-mechanical strength, and tissue engineering.

PMID- 29364650
TI  - Biological Nanopores: Confined Spaces for Electrochemical Single-Molecule
      Analysis.
AB  - Nanopore sensing is developing into a powerful single-molecule approach to
      investigate the features of biomolecules that are not accessible by studying
      ensemble systems. When a target molecule is transported through a nanopore, the
      ions occupying the pore are excluded, resulting in an electrical signal from the
      intermittent ionic blockade event. By statistical analysis of the amplitudes,
      duration, frequencies, and shapes of the blockade events, many properties of the
      target molecule can be obtained in real time at the single-molecule level,
      including its size, conformation, structure, charge, geometry, and interactions
      with other molecules. With the development of the use of alpha-hemolysin to
      characterize individual polynucleotides, nanopore technology has attracted a wide
      range of research interest in the fields of biology, physics, chemistry, and
      nanoscience. As a powerful single-molecule analytical method, nanopore technology
      has been applied for the detection of various biomolecules, including
      oligonucleotides, peptides, oligosaccharides, organic molecules, and disease
      related proteins. In this Account, we highlight recent developments of biological
      nanopores in DNA-based sensing and in studying the conformational structures of
      DNA and RNA. Furthermore, we introduce the application of biological nanopores to
      investigate the conformations of peptides affected by charge, length, and dipole
      moment and to study disease-related proteins' structures and aggregation
      transitions influenced by an inhibitor, a promoter, or an applied voltage. To
      improve the sensing ability of biological nanopores and further extend their
      application to a wider range of molecular sensing, we focus on exploring novel
      biological nanopores, such as aerolysin and Stable Protein 1. Aerolysin exhibits
      an especially high sensitivity for the detection of single oligonucleotides both
      in current separation and duration. Finally, to facilitate the use of nanopore
      measurements and statistical analysis, we develop an integrated current
      measurement system and an accurate data processing method for nanopore sensing.
      The unique geometric structure of a biological nanopore offers a distinct
      advantage as a nanosensor for single-molecule sensing. The construction of the
      pore entrance is responsible for capturing the target molecule, while the lumen
      region determines the translocation process of the single molecule. Since the
      capture of the target molecule is predominantly diffusion-limited, it is expected
      that the capture ability of the nanopore toward the target analyte could be
      effectively enhanced by site-directed mutations of key amino acids with desirable
      groups. Additionally, changing the side chains inside the wall of the biological
      nanopore could optimize the geometry of the pore and realize an optimal
      interaction between the single-molecule interface and the analyte. These
      improvements would allow for high spatial and current resolution of nanopore
      sensors, which would ensure the possibility of dynamic study of single
      biomolecules, including their metastable conformations, charge distributions, and
      interactions. In the future, data analysis with powerful algorithms will make it
      possible to automatically and statistically extract detailed information while an
      analyte translocates through the pore. We conclude that these improvements could
      have tremendous potential applications for nanopore sensing in the near future.

PMID- 29364651
TI  - Comparison of the Chemical Composition of Dissolved Organic Matter in Three Lakes
      in Minnesota.
AB  - New information on the chemical composition of dissolved organic matter (DOM) in
      three lakes in Minnesota has been gained from spectral editing and two
      dimensional nuclear magnetic resonance (NMR) methods, indicating the effects of
      lake hydrological settings on DOM composition. Williams Lake (WL), Shingobee Lake
      (SL), and Manganika Lake (ML) had different source inputs, and the lake water
      residence time (WRT) of WL was markedly longer than that of SL and ML. The
      hydrophobic organic acid (HPOA) and transphilic organic acid (TPIA) fractions
      combined comprised >50% of total DOM in these lakes, and contained carboxyl-rich
      alicyclic molecules (CRAM), aromatics, carbohydrates, and N-containing compounds.
      The previously understudied TPIA fractions contained fewer aromatics, more oxygen
      rich CRAM, and more N-containing compounds compared to the corresponding HPOA.
      CRAM represented the predominant component in DOM from all lakes studied, and
      more so in WL than in SL and ML. Aromatics including lignin residues and phenols
      decreased in relative abundances from ML to SL and WL. Carbohydrates and N
      containing compounds were minor components in both HPOA and TPIA and did not show
      large variations among the three lakes. The increased relative abundances of CRAM
      in DOM from ML, SL to WL suggested the selective preservation of CRAM with
      increased residence time.

PMID- 29364652
TI  - Residue Analysis of 60 Pesticides in Red Swamp Crayfish Using QuEChERS with High
      Performance Liquid Chromatography-Tandem Mass Spectrometry.
AB  - In this study, a multi-residue analytical method using quick, easy, cheap,
      effective, rugged, and safe (QuEChERS) extraction and dispersive solid-phase
      extraction (d-SPE) cleanup, followed by high-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS), was investigated for rapid determination
      of 60 pesticide residues in whole crayfish and crayfish meat. The final method
      used 10 mL of acetonitrile for extraction, 3 g of NaCl for partitioning, and 50
      mg of primary secondary amine for d-SPE cleanup. The method was validated at
      three spiking levels (10, 50, and 100 ng/g) using triphenyl phosphate as an
      internal standard and both gradient and isocratic HPLC elution. Under gradient
      conditions, satisfactory recoveries (70-120%) and relative standard deviations of
      <=20% were achieved for 83 and 88% of pesticides in whole crayfish and crayfish
      meat, respectively. Matrix effects were estimated using both gradient and
      isocratic HPLC elution. To our knowledge, this is the first study involving multi
      residue analysis of HPLC-amenable pesticides in crayfish and mantis shrimp. The
      final method was successfully applied for analysis of 11 crayfish and mantis
      shrimp samples from markets in China, and propamocarb (<limit of quantitation)
      and difenoconazole (8 ng/g) were detected in two different mantis shrimps.

PMID- 29364653
TI  - Simultaneous Multiselective Spectroelectrochemical Fiber-Optic Sensor: Sensing
      with an Optically Transparent Electrode.
AB  - We present a spectroelectrochemical fiber-optic sensor with an optically
      transparent electrode. The sensor was fabricated by coating indium tin oxide
      (ITO) onto the surface of fiber-optic core chips using a polygonal barrel
      sputtering method. The ITO-coated fiber-optic probe can be simply and cheaply
      mass-produced and used as a disposable probe. The sensing is based on changes in
      an attenuated total reflection signal accompanying the electrochemical oxidation
      reduction of an analyte at the electrode. The properties of an ITO-coated fiber
      optic probe as an optically transparent electrode were investigated for varying
      thicknesses of ITO. The sensor responses were successfully enhanced with an
      additional level of selectivity via an electrostatically adsorbed, self-assembled
      monolayer, which comprised a polyanion and polycation.

PMID- 29364654
TI  - Single-Crystal-to-Single-Crystal Postsynthetic Modification of a Metal-Organic
      Framework via Ozonolysis.
AB  - We describe solid-gas phase, single-crystal-to-single-crystal, postsynthetic
      modifications of a metal-organic framework (MOF). Using ozone, we quantitatively
      transformed the olefin groups of a UiO-66-type MOF into 1,2,4-trioxolane rings,
      which we then selectively converted into either aldehydes or carboxylic acids.

PMID- 29364655
TI  - Pesticide Residues in Table Grapes and Exposure Assessment.
AB  - This report describes levels of 172 pesticide residues in table grapes in Turkey.
      A total of 280 samples of table grapes were collected from supermarkets, bazaar,
      and greengrocer shops located in four provinces of Turkey from August to October
      2016. The samples were analyzed by liquid chromatography coupled to tandem mass
      spectrometry. The limit of quantification ranged from 0.002 to 0.010 mg kg-1. The
      validation data revealed good recoveries and good repeatability and
      reproducibility and fulfilled the other requirements of the European
      SANTE/11945/2015 Guideline. One or more pesticide residues were detected in 59.6%
      of the table grapes. The residues above the EU maximum residue levels were 20.4%
      of the samples. The most prevalent pesticide residues were azoxystrobin,
      chlorpyrifos, boscalid, and cyprodinil. Left-censored results (40.4% of the
      results) were substituted by lower bound , middle bound, and upper bound values.
      In the worst-case scenario, the hazard index (HI) was 3.37% for adults and 9.42%
      for children. Chlorpyrifos was the major contributor (65%) to HI.

PMID- 29364656
TI  - Hydration Energies and Reactivity of the Hypohalite Anions.
AB  - Herein is a dissection of the energetic contributions to a correlation between
      the rates and driving forces for oxygen atom transfer from three inorganic
      peroxides to the halides. Experimental data are used to calculate conventional
      and absolute hydration enthalpies for OCl-, OBr-, and OI-. It is found that the
      hydration enthalpies are more exothermic for the OX- species in comparison to
      their X- congeners, and it is found that the hydration enthalpies are
      approximately constant on progressing from OCl- to OI-. Both of these trends are
      contrary to expectations based on simple models of ionic hydration. Similar
      trends are seen in the Gibbs energies of hydration. The strong decrease in E
      degrees  from OCl- to OI- is seen to arise primarily from these differing trends
      in hydration energies rather than the gas-phase oxygen atom affinities of the
      halides. These effects show that the Marcus-like driving-force dependence for
      oxygen atom transfer from peroxides to the halides arises from the differing
      trends in hydration energies rather than in the intrinsic O-X- bond strengths.

PMID- 29364657
TI  - Identification of Pulmonary Edema in Forensic Autopsy Cases of Sudden Cardiac
      Death Using Fourier Transform Infrared Microspectroscopy: A Pilot Study.
AB  - Many studies have proven the usefulness of biofluid-based infrared spectroscopy
      in the clinical domain for diagnosis and monitoring the progression of diseases.
      Here we present a state-of-the-art study in the forensic field that employed
      Fourier transform infrared microspectroscopy for postmortem diagnosis of sudden
      cardiac death (SCD) by in situ biochemical investigation of alveolar edema fluid
      in lung tissue sections. The results of amide-related spectral absorbance
      analysis demonstrated that the pulmonary edema fluid of the SCD group was richer
      in protein components than that of the neurologic catastrophe (NC) and lethal
      multiple injuries (LMI) groups. The complementary results of unsupervised
      principle component analysis (PCA) and genetic algorithm-guided partial least
      squares discriminant analysis (GA-PLS-DA) further indicated different global
      spectral band patterns of pulmonary edema fluids between these three groups.
      Ultimately, a random forest (RF) classification model for postmortem diagnosis of
      SCD was built and achieved good sensitivity and specificity scores of 97.3% and
      95.5%, respectively. Classification predictions of unknown pulmonary edema fluid
      collected from 16 cases were also performed by the model, resulting in 100%
      correct discrimination. This pilot study demonstrates that FTIR microspectroscopy
      in combination with chemometrics has the potential to be an effective aid for
      postmortem diagnosis of SCD.

PMID- 29364659
TI  - Chiral Functionalization of a Zirconium Metal-Organic Framework (DUT-67) as a
      Heterogeneous Catalyst in Asymmetric Michael Addition Reaction.
AB  - DUT-67, an 8-connected zirconium and 2,5-thiophenedicarboxylate-based metal
      organic framework (MOF), was postsynthetically functionalized by l-proline via
      solvent-assisted linker incorporation to obtain a chiral base catalyst. The
      parent monocarboxylate could be almost completely exchanged by l-proline after 5
      days of treatment. The resulting chiral DUT-67 was demonstrated to be a promising
      heterogeneous catalyst for the asymmetric Michael addition of cyclohexanone to
      trans-beta-nitrostyrene with excellent yield (up to 96%) and enantioselectivity
      comparable to that of l-proline in homogeneous reaction (ee of approximately
      38%). The Zr-MOF could be reused at least five times without substantial
      degradation in the crystallinity or catalytic activity. No leaching of
      catalytically active species into the liquid phase was detected over five cycles.

PMID- 29364658
TI  - Metabonomics Indicates Inhibition of Fatty Acid Synthesis, beta-Oxidation, and
      Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in
      Male Mice.
AB  - Triclocarban (TCC) has been identified as a new environmental pollutant that is
      potentially hazardous to human health; however, the effects of short-term TCC
      exposure on cardiac function are not known. The aim of this study was to use
      metabonomics and molecular biology techniques to systematically elucidate the
      molecular mechanisms of TCC-induced effects on cardiac function in mice. Our
      results show that TCC inhibited the uptake, synthesis, and oxidation of fatty
      acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic
      glycolysis levels in heart tissue after short-term TCC exposure. TCC also
      inhibited the nuclear peroxisome proliferator-activated receptor alpha
      (PPARalpha), confirming its inhibitory effects on fatty acid uptake and
      oxidation. Histopathology and other analyses further confirm that TCC altered
      mouse cardiac physiology and pathology, ultimately affecting normal cardiac
      metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful
      effects on mouse cardiac metabolism and function from a new perspective, using
      metabonomics and bioinformatics analysis data.

PMID- 29364660
TI  - Combining Holographic Optical Tweezers with Upconversion Luminescence Encoding:
      Imaging-Based Stable Suspension Array for Sensitive Responding of Dual Cancer
      Biomarkers.
AB  - Establishment of a stable analytical methodology with high-quality results is an
      urgent need for screening cancer biomarkers in early diagnosis of cancer. In this
      study, we incorporate holographic optical tweezers with upconversion luminescence
      encoding to design an imageable suspension array and apply it to conduct the
      detection of two liver cancer related biomarkers, carcinoembryonic antigen and
      alpha fetal protein. This bead-based assay is actualized by forming a bead array
      with holographic optical tweezers and synchronously exciting the upconversion
      luminescence of corresponding trapped complex beads fabricated with a simple one
      step sandwich immunological recognition. Owing to the fact that these flowing
      beads are stably trapped in the focal plane of the objective lens which tightly
      converges the array of the laser beams by splitting a 980 nm beam using a
      diffraction optical element, a fairly stable excitation condition is achieved to
      provide reliable assay results. By further taking advantage of the eminent
      encoding capability of upconversion nanoparticles and the extremely low
      background signals of anti-Stokes luminescence, the two targets are well
      identified and simultaneously detected with quite sound sensitivity and
      specificity. Moreover, the potential on-demand clinical application is presented
      by employing this approach to respond the targets toward complex matrices such as
      serum and tissue samples, offering a new alternative for cancer diagnosis
      technology.

PMID- 29364662
TI  - Morphology of Anion-Conducting Ionenes Investigated by X-ray Scattering and
      Simulation.
AB  - We have studied the morphology of a novel series of benzimidazole-based ionenes,
      methylated poly(hexamethyl-p-terphenylbenzimidazolium) (HMT-PMBI), in halide
      form. Materials with anion-exchange capacities ranging from 0 to 2.5 mequiv/g
      were studied. X-ray scattering reveals three length scales in the materials: ion
      polymer spacing (4 A), polymer-polymer interchain spacing (6 A), and an
      intrachain repeat distance (20 A). No long-range structure is apparent above the
      monomer length, which is rare in ion-conducting polymer membranes. In preliminary
      molecular dynamics simulations, water molecules were observed forming chains
      between ions, even at a modest level of hydration, providing an interpenetrating
      network where conductivity can occur.

PMID- 29364661
TI  - Physical Biology of the Materials-Microorganism Interface.
AB  - Future solar-to-chemical production will rely upon a deep understanding of the
      material-microorganism interface. Hybrid technologies, which combine inorganic
      semiconductor light harvesters with biological catalysis to transform light, air,
      and water into chemicals, already demonstrate a wide product scope and energy
      efficiencies surpassing that of natural photosynthesis. But optimization to
      economic competitiveness and fundamental curiosity beg for answers to two basic
      questions: (1) how do materials transfer energy and charge to microorganisms, and
      (2) how do we design for bio- and chemocompatibility between these seemingly
      unnatural partners? This Perspective highlights the state-of-the-art and outlines
      future research paths to inform the cadre of spectroscopists, electrochemists,
      bioinorganic chemists, material scientists, and biologists who will ultimately
      solve these mysteries.

PMID- 29364663
TI  - Natural Products Containing a Nitrogen-Sulfur Bond.
AB  - Only about 100 natural products are known to contain a nitrogen-sulfur (N-S)
      bond. This review thoroughly categorizes N-S bond-containing compounds by
      structural class. Information on biological source, biological activity, and
      biosynthesis is included, if known. We also review the role of N-S bond
      functional groups as post-translational modifications of amino acids in proteins
      and peptides, emphasizing their role in the metabolism of the cell.

PMID- 29364664
TI  - Binding-Site Compatible Fragment Growing Applied to the Design of beta2
      Adrenergic Receptor Ligands.
AB  - Fragment-based drug discovery is intimately linked to fragment extension
      approaches that can be accelerated using software for de novo design. Although
      computers allow for the facile generation of millions of suggestions, synthetic
      feasibility is however often neglected. In this study we computationally
      extended, chemically synthesized, and experimentally assayed new ligands for the
      beta2-adrenergic receptor (beta2AR) by growing fragment-sized ligands. In order
      to address the synthetic tractability issue, our in silico workflow aims at
      derivatized products based on robust organic reactions. The study started from
      the predicted binding modes of five fragments. We suggested a total of eight
      diverse extensions that were easily synthesized, and further assays showed that
      four products had an improved affinity (up to 40-fold) compared to their
      respective initial fragment. The described workflow, which we call "growing via
      merging" and for which the key tools are available online, can improve early
      fragment-based drug discovery projects, making it a useful creative tool for
      medicinal chemists during structure-activity relationship (SAR) studies.

PMID- 29364665
TI  - Kinetics of Melanin Polymerization during Enzymatic and Nonenzymatic Oxidation.
AB  - Melanin is an abundant biopigment in the animal kingdom, but its structure
      remains poorly understood. This is a substantial impediment to understanding the
      mechanistic origin of its observed functions. Proposed models of melanin
      structure include aggregates of both linear and macrocyclic units and
      noncovalently held monomers. Both models are broadly in agreement with current
      experimental data. To constrain the structural and kinetic models of melanin,
      experimental data of high resolution with chemical specificity accompanied by
      atomistic modeling are required. We have addressed this by obtaining electronic
      absorption, infrared, and ultraviolet resonance Raman (RR) spectra of melanin at
      several wavelengths of excitation that are sensitive to small changes in
      structure. From these experiments, we observed kinetics of the formation of
      different species en route to melanin polymerization. Exclusive chemical
      signatures of monomer 3,4-dihydroxyphenylalanine (dopa), intermediate dopachrome
      (DC), and early-time polymer are established through their vibrational bands at
      1292, 1670, and 1616 cm-1 respectively. Direct evidence of reduced heterogeneity
      of melanin oligomers in tyrosinase-induced formation is provided from
      experimental measurements of vibrational bandwidths. Models made with density
      functional theory show that the linear homopolymeric structures of 5,6
      dihydroxyindole can account for experimentally observed wavenumbers and broad
      bandwidth in Raman spectra of dopa-melanin. We capture resonance Raman (RR)
      signature of DC, the intermediate stabilized by the enzyme tyrosinase, for the
      first time in an enzyme-assisted melanization reaction using 488 nm excitation
      wavelength and propose that this wavelength can be used to probe reaction
      intermediates of melanin formation in solution.

PMID- 29364666
TI  - Regioselective and Stereoselective Heck-Matsuda Arylations of Trisubstituted
      Allylic Alkenols and Their Silyl and Methyl Ether Derivatives To Access Two
      Contiguous Stereogenic Centers: Expanding the Redox-Relay Process and Application
      in the Total Synthesis of meso-Hexestrol.
AB  - Novel palladium-catalyzed redox-relay Heck arylation reactions of trisubstituted
      allylic alkenols were developed employing silyl and methyl ethers. The reactions
      proceeded under mild conditions in moderate to high yields in an excellent anti
      diastereoselectivity to form alpha,beta-disubstituted methyl ketones containing
      two contiguous stereocenters. The new redox-relay arylations using silyl and
      methyl ethers of the starting alkenols demonstrate that the presence of a free
      hydroxyl group is not a sine qua non condition for an effective redox-relay
      process as previously thought. Deuterium-labeled alkenols 2-d-10a, 2-d-10b, and 2
      d-10c permitted tracking the palladium-hydride reinsertion steps in the
      conversion of the starting free alcohols, silyl, and methyl ethers into the
      corresponding methyl ketone 3-d-11a, with >98% deuterium retention. Moreover, the
      synthetic potential of the method was demonstrated with a straightforward
      synthesis of the meso-hexestrol in 4 steps, in 41% overall yield from alkenol
      10a.

PMID- 29364667
TI  - Solvation of Methyl Lactate in Water: Molecular Dynamics Studies.
AB  - Methyl lactate (ML), a chiral alpha-hydroxy ester, has been probed widely to
      understand the competition between two types of intramolecular H-bonds in
      solvents of different polarities. Recent experimental and high-level quantum
      chemical studies have revealed the predominant existence of ML-water insertion
      complexes over addition complexes in aqueous solution. Although the stability of
      monohydrate insertion conformer was studied accurately, ab initio quantum
      chemical calculations failed to predict the most stable dihydrate conformer in
      analogy with the experimental spectroscopic search. Atomistic molecular dynamics
      simulations of aqueous solution of methyl lactate predict that the population and
      lifetime of different H-bonded ML-water addition complexes are dictated by their
      interaction energies. Although the population of dihydrate insertion complexes is
      higher than that of the monohydrate complexes, the lifetime of the former is
      smaller than the latter, which is in good agreement with the experimental result.
      The nature of intramolecular H-bonds within a methyl lactate molecule in aqueous
      solution is opposite to that in the gas phase due to the solvation process in
      water by intermolecular H-bonding interactions.

PMID- 29364668
TI  - Probability and Flux Densities in the Center-of-Mass Frame.
AB  - For an arbitrary nonstationary wave function of a nonrelativistic closed many
      body system consisting of arbitrary interacting particles, the general
      expressions for the time-dependent one-particle probability and flux densities in
      the center-of-mass frame without applying Born-Oppenheimer approximation are
      obtained. Even the wave function for the translation is additionally introduced;
      it disappears in the center-of-mass frame automatically. It is shown that for the
      rotational ground state the time-dependent probability and flux densities of an
      arbitrary particle in the center-of-mass frame are isotropic. It means that the
      angular dependence is absent but these densities depend on radius and time. More
      importantly, it is shown that the angular components of the time-dependent flux
      density vanish. With these statements, one can calculate the radial component of
      the radius- and time-dependent electronic flux density within the Born
      Oppenheimer approximation via the continuity equation. Application of this theory
      to the pulsating or exploding "quantum bubble" of the vibrating or dissociating
      Na2 molecule in the rotational ground state, respectively, is found elsewhere in
      this issue.

PMID- 29364669
TI  - Revision of the Phytochemistry of Eremophila sturtii and E. mitchellii.
AB  - Eremophila sturtii and E. mitchellii are found in the arid and temperate regions
      of Australia and, because of their similar appearances, are often confused.
      Previous phytochemical investigations have described mitchellene sesquiterpenes
      (1-5) reported from E. mitchellii but are here demonstrated to be from E.
      sturtii. A previous study that described serrulatic acids (16 and 17) from a
      species reported as E. sturtii actually used E. mitchellii. In addition, two new
      C-15 modified analogues, mitchellenes F (14) and G (15), were isolated from E.
      sturtii. The absolute configuration of 14 was determined with the first X-ray
      structure of a compound with the mitchellene skeleton.

PMID- 29364670
TI  - Morphology-Preserving Sensitization of ZnO Nanorod Surfaces via Click-Chemistry.
AB  - Films of ZnO nanorods grown by chemical vapor deposition were functionalized with
      a chromophore in a stepwise process that preserves the surface morphology. In the
      first step, the ZnO nanorods were functionalized by exposure to prop-2-ynoic acid
      (propiolic acid) in vacuum, which did bind through the COOH group leading to a
      ZnO surface functionalized with ethyne moieties (ethyne/ZnO). In the second step,
      9-(4-azidophenyl)-2,5-di-tert-butylperylene (DTBPe-Ph-N3) was reacted with the
      ethyne/ZnO surface via copper-catalyzed azide-alkyne click reaction (CuAAC) in
      solution to form the DTBPe-functionalized surface (DTBPe/ZnO). The ZnO morphology
      was preserved after each step, as demonstrated by scanning electron microscopy
      (SEM). Each step was probed by X-ray photoelectron spectroscopy (XPS), and
      transient absorption spectroscopy (TA) of the resulting DTBPe/ZnO surface shows
      interfacial electron transfer following visible light excitation. As expected,
      attempts to bind the reference compound 1-(4-(8,11-ditert-butylperylen-3-yl)
      phenyl)-1H-1,2,3-triazole-4-carboxylic acid (DTBPe-Ph-Tz-COOH) directly from
      solution lead to etched surfaces (confirmed by SEM) and undefined binding modes
      (confirmed by TA).

PMID- 29364671
TI  - Na2 Vibrating in the Double-Well Potential of State 2 1Sigmau+ (JM = 00): A
      Pulsating "Quantum Bubble" with Antagonistic Electronic Flux.
AB  - The theory of concerted electronic and nuclear flux densities associated with the
      vibration and dissociation of a multielectron nonrotating homonuclear diatomic
      molecule (or ion) in an electronic state 2S+1Sigmag,u+ (JM = 00) is presented.
      The electronic population density, nuclear probability density, and nuclear flux
      density are isotropic. A theorem of Barth , presented in this issue, shows that
      the electronic flux density (EFD) is also isotropic. Hence, the evolving system
      appears as a pulsating, or exploding, "quantum bubble". Application of the theory
      to Na2 vibrating in the double-minimum potential of the 2  1Sigmau+ (JM = 00)
      excited state reveals that the EFD consists of two antagonistic components. One
      arises from electrons that flow essentially coherently with the nuclei. The
      other, which is oppositely directed (i.e., antagonistic) and more intense, is due
      to the transition in electronic structure from "Rydberg" to "ionic" type as the
      nuclei traverse the potential barrier between inner and outer potential wells.
      This "transition" component of the EFD rises and falls sharply as the nuclei
      cross the barrier.

PMID- 29364672
TI  - (R)-DM-SEGPHOS-Ag(I)-Catalyzed Enantioselective Synthesis of Pyrrolidines and
      Pyrrolizidines via (1,3)- and Double (1,3)-Dipolar Cycloaddition Reactions.
AB  - An efficient diastereo- and enantioselective route to access a wide range of
      highly substituted pyrrolidine and pyrrolizidine derivatives has been described
      via (1,3)- and double (1,3)-dipolar cycloaddition reactions catalyzed by the (R)
      DM-SEGPHOS-Ag(I) complex. The reactions proceed smoothly at ambient temperature,
      affording a variety of pyrrolidines and pyrrolizidines in high yields (up to 93%)
      with up to 99:1 dr and excellent enantioselectivities (up to 98% ee) without any
      additives. The newly synthesized pyrrolidine and pyrrolizidine derivatives
      contain four and seven contiguous stereogenic centers, respectively. Moreover,
      the synthetic utility of enantioenriched products has been demonstrated by
      transforming them into various synthetically useful advanced intermediates.

PMID- 29364673
TI  - Closed-Shell Organic Compounds Might Form Dimers at the Surface of Molecular
      Clusters.
AB  - The role of covalently bound dimer formation is studied using high-level quantum
      chemical methods. Reaction free energy profiles for dimer formation between
      common oxygen-containing functional groups are calculated, and based on the Gibbs
      free energy differences between transition states and reactants, we show that
      none of the studied two-component gas-phase reactions are kinetically feasible at
      298.15 K and 1 atm. Therefore, the catalyzing effect of water, base, or acid
      molecules is calculated, and sulfuric acid is identified to lower the activation
      free energies significantly. We find that the reactions yielding hemiacetal,
      peroxyhemiacetal, alpha-hydroxyester, and geminal diol products occur with
      activation free energies of less than 10 kcal/mol with sulfuric acid as a
      catalyst, indicating that these reactions could potentially take place on the
      surface of sulfuric acid clusters. Additionally, the formed dimer products bind
      stronger onto the pre-existing cluster than the corresponding reagent monomers
      do. This implies that covalent dimerization reactions stabilize the existing
      cluster thermodynamically and make it less likely to evaporate. However, the
      studied small organic compounds, which contain only one functional group, are not
      able to form dimer products that are stable against evaporation at atmospheric
      conditions. Calculations of dimer formation onto a cluster surface and the
      clustering ability of dimer products should be extended to large terpene
      oxidation products in order to estimate the real atmospheric significance.

PMID- 29364674
TI  - C2'-F Stereoconfiguration As a Puckering Switch for Base Stacking at the
      Dinucleotide Level.
AB  - Fluorine configuration at C2' of the bis(2'-fluorothymidine) dinucleotide is
      demonstrated to drive intramolecular base stacking. 2'-beta F-Configuration
      drastically reduces stacking compared to the 2'-alpha series. Hence, base
      stacking emerges as being tunable by the C2'-F stereoconfiguration through
      dramatic puckering variations scrutinized by NMR and natural bond orbital
      analysis. Accordingly, 2'-beta F-isomer photoreactivity is significantly reduced
      compared to that of the 2'-alpha F-isomer.

PMID- 29364675
TI  - Adsorption of Bovine Serum Albumin on Poly(vinylidene fluoride) Surfaces in the
      Presence of Ions: A Molecular Dynamics Simulation.
AB  - Adsorption of bovine serum albumin (BSA) on poly(vinylidene fluoride) (PVDF)
      surfaces in an aqueous environment was investigated in the presence and absence
      of excess ions using molecular dynamics simulations. The adsorption process
      involved diffusion of protein to the surface and dehydration of surface-protein
      interactions, followed by adsorption and denaturation. Although adsorption of BSA
      on PVDF surface was observed in the absence of excess ions, denaturation of BSA
      was not observed during the simulation (1 MUs). Basic and acidic amino acids of
      BSA were found to be directly interacting with PVDF surface. Simulation in a 0.1
      M NaCl solution showed delayed adsorption of BSA on PVDF surfaces in the presence
      of excess ions, with BSA not observed in close proximity to PVDF surface within
      700 ns. Adsorption of Cl- on PVDF surface increased its negative charge, which
      repelled negatively charged BSA, thereby delaying the adsorption process. These
      results will be helpful for understanding membrane fouling phenomena in polymeric
      membranes, and fundamental advancements in these areas will lead to a new
      generation of membrane materials with improved antifouling properties and reduced
      energy demands.

PMID- 29364676
TI  - Control of Energy Flow Dynamics between Tetracene Ligands and PbS Quantum Dots by
      Size Tuning and Ligand Coverage.
AB  - We have prepared a series of samples with the ligand 6,13-bistri(iso
      propyl)silylethynyl tetracene 2-carboxylic acid (TIPS-Tc-COOH) attached to PbS
      quantum dot (QD) samples of three different sizes in order to monitor and control
      the extent and time scales of energy flow after photoexcitation. Fast energy
      transfer (~1 ps) to the PbS QD occurs upon direct excitation of the ligand for
      all samples. The largest size QD maintains the microsecond exciton lifetime
      characteristic of the as-prepared oleate terminated PbS QDs. However, two smaller
      QD sizes with lowest exciton energies similar to or larger than the TIPS-Tc-COO-
      triplet energy undergo energy transfer between QD core and ligand triplet on
      nanosecond to microsecond timescales. For the intermediate size QDs in
      particular, energy can be recycled many times between ligand and core, but the
      triplet remains the dominant excited species at long times, living for ~3 MUs for
      fully exchanged QDs and up to 30 MUs for partial ligand exchange, which is
      revealed as a method for controlling the triplet lifetime. A unique upconverted
      luminescence spectrum is observed that results from annihilation of triplets
      after exclusive excitation of the QD core.

PMID- 29364677
TI  - Fabrication of Biomimetic Fog-Collecting Superhydrophilic-Superhydrophobic
      Surface Micropatterns Using Femtosecond Lasers.
AB  - The exciting functionalities of natural superhydrophilic and superhydrophobic
      surfaces served as inspiration for a variety of biomimetic designs. In
      particular, the combination of both extreme wetting states to micropatterns opens
      up interesting applications, as the example of the fog-collecting Namib Desert
      beetle shows. In this paper, the beetle's elytra were mimicked by a novel three
      step fabrication method to increase the fog-collection efficiency of glasses. In
      the first step, a double-hierarchical surface structure was generated on Pyrex
      wafers using femtosecond laser structuring, which amplified the intrinsic wetting
      property of the surface and made it superhydrophilic (water contact angle < 10
      degrees ). In the second step, a Teflon-like polymer (CF2) n was deposited by a
      plasma process that turned the laser-structured surface superhydrophobic (water
      contact angle > 150 degrees ). In the last step, the Teflon-like coating was
      selectively removed by fs-laser ablation to uncover superhydrophilic spots below
      the superhydrophobic surface, following the example of the Namib Desert beetle's
      fog-collecting elytra. To investigate the influence on the fog-collection
      behavior, (super)hydrophilic, (super)hydrophobic, and low and high contrast
      wetting patterns were fabricated on glass wafers using selected combinations of
      these three processing steps and were exposed to fog in an artificial nebulizer
      setup. This experiment revealed that high-contrast wetting patterns collected the
      highest amount of fog and enhanced the fog-collection efficiency by nearly 60%
      compared to pristine Pyrex glass. The comparison of the fog-collection behavior
      of the six samples showed that the superior fog-collection efficiency of surface
      patterns with extreme wetting contrast is due to the combination of water
      attraction and water repellency: the superhydrophilic spots act as drop
      accumulation areas, whereas the surrounding superhydrophobic areas allow a fast
      water transportation caused by gravity. The presented method enables a fast and
      flexible surface functionalization of a broad range of materials including
      transparent substrates, which offers exciting possibilities for the design of
      biomedical and microfluidic devices.

PMID- 29364678
TI  - Fluvirosaones A and B, Two Indolizidine Alkaloids with a Pentacyclic Skeleton
      from Flueggea virosa.
AB  - Fluvirosaones A (1) and B (2), together with virosecurinine (3), were isolated
      from Flueggea virosa. Their structures were determined by physical,
      spectroscopic, and X-ray analysis and confirmed through comparison of the
      calculated and experimental 13C NMR and electronic circular dichroism (ECD) data.
      Compounds 1 and 2 represent the first examples of a pentacyclic Securinega
      alkaloid containing a pentacyclic system and an alpha,beta-unsaturated ketone.
      Plausible biogenetic pathways of compounds 1 and 2 are proposed.

PMID- 29364679
TI  - Self-Assembled PCBM Nanosheets: A Facile Route to Electronic Layer-on-Layer
      Heterostructures.
AB  - We report on the self-assembly of semicrystalline [6,6]-phenyl-C61-butyric acid
      methyl ester (PCBM) nanosheets at the interface between a hydrophobic solvent and
      water, and utilize this opportunity for the realization of electronically active
      organic/organic molecular heterostructures. The self-assembled PCBM nanosheets
      can feature a lateral size of >1 cm2 and be transferred from the water surface to
      both hydrophobic and hydrophilic surfaces using facile transfer techniques. We
      employ a transferred single PCBM nanosheet as the active material in a field
      effect transistor (FET) and verify semiconductor function by a measured electron
      mobility of 1.2 * 10-2 cm2 V-1 s-1 and an on-off ratio of ~1 * 104. We further
      fabricate a planar organic/organic heterostructure with the p-type organic
      semiconductor poly(3-hexylthiophene-2,5-diyl) as the bottom layer and the n-type
      PCBM nanosheet as the top layer and demonstrate ambipolar FET operation with an
      electron mobility of 8.7 * 10-4 cm2 V-1 s-1 and a hole mobility of 3.1 * 10-4 cm2
      V-1 s-1.

PMID- 29364681
TI  - Aza-Diels-Alder Approach to Diquinolineanthracene and Polydiquinolineanthracene
      Derivatives.
AB  - This study describes the synthesis of modular diquinolineanthracene and
      polydiquinolineanthracene derivatives. The reported facile and scalable aza-Diels
      Alder-based approach requires mild conditions, proceeds in two steps, uses
      commercially available starting materials, and accommodates varying
      functionalities. Given the known utility of the acene and quinoline motifs, the
      synthesized molecules and polymers hold promise for organic electronics
      applications.

PMID- 29364680
TI  - Exploration of the Fecal Microbiota and Biomarker Discovery in Equine Grass
      Sickness.
AB  - Equine grass sickness (EGS) is a frequently fatal disease of horses, responsible
      for the death of 1 to 2% of the U.K. horse population annually. The etiology of
      this disease is currently uncharacterized, although there is evidence it is
      associated with Clostridium botulinum neurotoxin in the gut. Prevention is
      currently not possible, and ileal biopsy diagnosis is invasive. The aim of this
      study was to characterize the fecal microbiota and biofluid metabolic profiles of
      EGS horses, to further understand the mechanisms underlying this disease, and to
      identify metabolic biomarkers to aid in diagnosis. Urine, plasma, and feces were
      collected from horses with EGS, matched controls, and hospital controls.
      Sequencing the16S rRNA gene of the fecal bacterial population of the study horses
      found a severe dysbiosis in EGS horses, with an increase in Bacteroidetes and a
      decrease in Firmicutes bacteria. Metabolic profiling by 1H nuclear magnetic
      resonance spectroscopy found EGS to be associated with the lower urinary
      excretion of hippurate and 4-cresyl sulfate and higher excretion of O-acetyl
      carnitine and trimethylamine-N-oxide. The predictive ability of the complete
      urinary metabolic signature and using the four discriminatory urinary metabolites
      to classify horses by disease status was assessed using a second (test) set of
      horses. The urinary metabolome and a combination of the four candidate biomarkers
      showed promise in aiding the identification of horses with EGS. Characterization
      of the metabolic shifts associated with EGS offers the potential of a noninvasive
      test to aid premortem diagnosis.

PMID- 29364682
TI  - Total Synthesis of ent-Pregnanolone Sulfate and Its Biological Investigation at
      the NMDA Receptor.
AB  - A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone,
      as well as a study of its biological activity at the NMDA receptor, is reported.
      The asymmetry is introduced by a highly atom-economic organocatalytic Robinson
      annulation. A new method for the construction of the cyclopentane D-ring
      consisting of CuI-catalyzed conjugate addition and oxygenation followed by
      thermal cyclization employing the persistent radical effect was developed. ent
      Pregnanolone sulfate is surprisingly only 2.6-fold less active than the natural
      neurosteroid.

PMID- 29364683
TI  - Programmable Assembly of Hybrid Nanoclusters.
AB  - Hybrid nanoparticle clusters (often metallic) are interesting plasmonic materials
      with tunable resonances and a near-field electromagnetic enhancement at
      interparticle junctions. Therefore, in recent years, we have witnessed a surge in
      both the interest in these materials and the efforts to obtain them. However, a
      versatile fabrication of hybrid nanoclusters, that is, combining more than one
      material, still remains an open challenge. Current lithographical or self
      assembly methods are limited to the preparation of hybrid clusters with up to two
      different materials and typically to the fabrication of hybrid dimers. Here, we
      provide a novel strategy to deposit and align not only hybrid dimers but also
      hybrid nanoclusters possessing more complex shapes and compositions. Our strategy
      is based on the downscaling of sequential capillarity-assisted particle assembly
      over topographical templates. As a proof of concept, we demonstrate dimers,
      linear trimers, and 2D nanoclusters with programmable compositions from a range
      of metallic nanoparticles. Our process does not rely on any specific chemistry
      and can be extended to a large variety of particles and shapes. The template also
      simultaneously aligns the hybrid (often anisotropic) nanoclusters, which could
      facilitate device integration, for example, for optical readout after transfer to
      other substrates by a printing step. We envisage that this new fabrication route
      will enable the assembly and positioning of complex hybrid nanoclusters of
      different functional nanoparticles to study coupling effects not only locally but
      also at larger scales for new nanoscale optical devices.

PMID- 29364684
TI  - Rhodium(I)-Catalyzed Decarbonylative Aerobic Oxidation of Cyclic alpha-Diketones:
      A Regioselective Single Carbon Extrusion Strategy.
AB  - A rhodium-catalyzed decarbonylative aerobic oxidation of cyclic alpha-diketones
      has been developed for the first time, where the regioselective formations of
      alpha-pyrones and isocoumarins have been achieved. The current decarbonylative
      aerobic oxidation pathway proceeds via the C-C bond cleavage followed by a C-O
      bond formation, representing a biomimetic oxidation approach to unsaturated six
      membered cyclic lactones. The unique ability of rhodium catalysts to induce the
      decarbonylative aerobic oxidation opens up a new synthetic toolbox that utilizes
      the "regioselective single carbon" extrusion strategy.

PMID- 29364685
TI  - Direct C-H Cyanoalkylation of Quinoxalin-2(1H)-ones via Radical C-C Bond
      Cleavage.
AB  - An efficient synthesis of cyanoalkylated heteroarenes via iron-catalyzed direct C
      H cyanoalkylation of heteroarenes has been developed. Structurally diverse
      cyanoalkyl motifs generated through C-C bond cleavage of cyclobutanone oxime
      esters have been introduced into quinoxalin-2(1H)-ones, flavone, benzothiazoles,
      and caffeine in good to excellent yields. Remarkably, less-strained
      cyclopentanone and unstrained cyclohexanone oxime esters were also amenable
      substrates in this cyanoalkylation reaction.

PMID- 29364686
TI  - Mass Exchange and Equilibration Processes in AOT Reverse Micelles.
AB  - Reverse micelles (RMs) made with sodium bis(2-ethylhexyl)sulfosuccinate suspended
      in isooctane are commonly used experimental models of aqueous microenvironments.
      However, there are important unanswered questions about the very characteristic
      that makes them of interest, namely their size. To explore the factors that
      determine the size of RMs, all-atom molecular dynamics simulations of RMs with
      different sizes but the same water-loading ratio were performed. An Anton 2
      machine was used so that systems of the necessary size could be extended into the
      microsecond timescale, and mass exchange processes could be observed. Contrary to
      hypothesis, there were no net gains or losses of water by diffusion between RMs
      of different size. However, gains and losses did occur following fusion events.
      RM fusion followed RM contact only when waters were present among the hydrophobic
      surfactant chains at the point of contact. The presence of an encapsulated 40
      residue amyloid beta peptide did not directly promote RM fusion, but it quickly
      and efficiently terminated each fusion event. Before fusion terminated, however,
      the size of the peptide-containing RM increased without a corresponding change in
      its water-loading ratio. We conclude that the mass transfer between RMs is most
      likely accomplished through transient fusion events, rather than through the
      diffusion of component molecules through the organic phase. The behavior of the
      amyloid beta peptide in this system underscores its propensity to embed in, and
      fold in response to, multiple interactions with the surfactant layer.

PMID- 29364687
TI  - Electron Correlation in the Ionization Continuum of Molecules: Photoionization of
      N2 in the Vicinity of the Hopfield Series of Autoionizing States.
AB  - Direct measurement of autoionization lifetimes by using time-resolved
      experimental techniques is a promising approach when energy-resolved
      spectroscopic methods do not work. Attosecond time-resolved experiments have
      recently provided the first quantitative determination of autoionization
      lifetimes of the lowest members of the well-known Hopfield series of resonances
      in N2. In this work, we have used the recently developed XCHEM approach to study
      photoionization of the N2 molecule in the vicinity of these resonances. The XCHEM
      approach allows us to describe electron correlation in the molecular electronic
      continuum at a level similar to that provided by multireference configuration
      interaction methods in bound state calculations, a necessary condition to
      accurately describe autoionization, shakeup, and interchannel couplings occurring
      in this range of photon energies. Our results show that electron correlation
      leading to interchannel mixing is the main factor that determines the magnitude
      and shape of the N2 photoionization cross sections, as well as the lifetimes of
      the Hopfield resonances. At variance with recent speculations, nonadiabatic
      effects do not seem to play a significant role. These conclusions are supported
      by the very good agreement between the calculated cross sections and those
      determined in synchrotron radiation and attosecond experiments.

PMID- 29364688
TI  - Ru-Catalyzed Chemoselective Olefin Migration Reaction of Cyclic Allylic Acetals
      to Enol Acetals.
AB  - A Ru-catalyzed olefin migration reaction of chiral cyclic allylic acetal is
      reported. The reaction generates cyclic enol acetal in a highly chemoselective
      manner. A variety of O,O- and N,O-acetals participated in the reaction with
      conservation of the stereochemical integrity of the acetal moiety. The utility of
      the reaction was demonstrated by the short and protective group-free syntheses of
      (L)-deoxyribonucleoside and beta-amicetose glycoside.

PMID- 29364690
TI  - Improving the Cell Permeability of Polar Cyclic Peptides by Replacing Residues
      with Alkylated Amino Acids, Asparagines, and d-Amino Acids.
AB  - The design, synthesis, and cell permeability of 19 hydrophilic macrocyclic
      peptides is presented. By systematically analyzing the impact of three different
      approaches (alkylated amino acids, asparagines, and d-amino acids) on the
      permeability of polar peptides, a well-defined strategy for optimizing cell
      permeability is provided. These three new methods can be used individually or in
      combination to effectively convert polar peptides into cell permeable molecules,
      and the results can be applied to the rapidly expanding peptide therapeutic
      industry.

PMID- 29364689
TI  - Microfluidic Tensiometry Technique for the Characterization of the Interfacial
      Tension between Immiscible Liquids.
AB  - The interfacial tension between two immiscible fluids is of critical importance
      for understanding many natural phenomena as well as in industrial production
      processes; however, it can be challenging to measure this parameter with high
      accuracy. Most commonly used techniques have significant shortcomings because of
      their reliance on other data such as density or viscosity. To overcome these
      issues, we devise a technique that works with very small sample quantities and
      does not require any data about either fluid, based on micropipette aspiration
      techniques. The method facilitates the generation of a droplet of one fluid
      inside of the other, followed by immediate in situ aspiration of the droplet into
      a constricted channel. A modified Young-Laplace equation is then used to relate
      the pressure needed to produce a given deformation of the droplet's radius to the
      interfacial tension. We demonstrate this technique on different systems with
      interfacial tensions ranging from sub-millinewton per meter to several hundred
      millinewton per meter, thus over 4 orders of magnitude, obtaining precise results
      in agreement with the literature solely from experimental observations of the
      droplet deformation.

PMID- 29364691
TI  - Structure of a Multilayer Nanofilm To Increase the Encapsulation Efficiency of
      Basic Fibroblast Growth Factor.
AB  - In this study, we established the structure of a multilayer nanofilm that more
      efficiently encapsulates basic fibroblast growth factor (bFGF). First, a
      positively charged layer material was selected from biocompatible polymers such
      as collagen (Col), poly(beta-amino ester) (Poly2), and chitosan (Chi), while
      considering the film thickness. We then investigated the change in bFGF
      encapsulation efficiency when the multilayer structure was changed from a
      tetralayer to a trilayer. As a result, we obtained a highly improved bFGF
      encapsulation efficiency in the nanofilm using a positively charged layer formed
      by a blend of Col and Poly2 and a negatively charged poly(acrylic acid) (PAA)
      layer within a trilayered structure. In particular, we found that a significant
      amount of adsorbed bFGF was desorbed again during the film fabrication process of
      a tetralayered nanofilm. In the conventional nanofilm, bFGF was regarded as a
      polycation and formed a multilayer nanofilm that was composed of a tetralayered
      structure and was represented as (polycation/polyanion/bFGF/polyanion) n where n
      = number of repeated tetralayers. Here, we suggested that bFGF should not be
      considered a polycation, rather it should be considered as a small quantity of
      molecule that exists between the polyanion and polycation layers. In this case,
      the nanofilm is composed of repeating units of
      (polycation/polyanion/bFGF/polycation/polyanion), because the amount of adsorbed
      bFGF is considerably lower than that of other building blocks.

PMID- 29364692
TI  - Development of Annealing-Free, Solution-Processable Inverted Organic Solar Cells
      with N-Doped Graphene Electrodes using Zinc Oxide Nanoparticles.
AB  - An annealing-free process is considered as a technological advancement for the
      development of flexible (or wearable) organic electronic devices, which can
      prevent the distortion of substrates and damage to the active components of the
      device and simplify the overall fabrication process to increase the industrial
      applications. Owing to its outstanding electrical, optical, and mechanical
      properties, graphene is seen as a promising material that could act as a
      transparent conductive electrode for flexible optoelectronic devices. Owing to
      their high transparency and electron mobility, zinc oxide nanoparticles (ZnO-NP)
      are attractive and promising for their application as charge transporting
      materials for low-temperature processes in organic solar cells (OSCs),
      particularly because most charge transporting materials require annealing
      treatments at elevated temperatures. In this study, graphene/annealing-free ZnO
      NP hybrid materials were developed for inverted OSC by successfully integrating
      ZnO-NP on the hydrophobic surface of graphene, thus aiming to enhance the
      applicability of graphene as a transparent electrode in flexible OSC systems.
      Chemical, optical, electrical, and morphological analyses of ZnO-NPs showed that
      the annealing-free process generates similar results to those provided by the
      conventional annealing process. The approach was effectively applied to graphene
      based inverted OSCs with notable power conversion efficiencies of 8.16% and 7.41%
      on the solid and flexible substrates, respectively, which promises the great
      feasibility of graphene for emerging optoelectronic device applications.

PMID- 29364693
TI  - Examining Insomnia and PTSD Over Time in Veterans in Residential Treatment for
      Substance Use Disorders and PTSD.
AB  - OBJECTIVE/BACKGROUND: Insomnia occurs in 66-90% of individuals with posttraumatic
      stress disorder (PTSD) and 36-72% of individuals with substance use disorder
      (SUD). Individuals with both PTSD and SUD are more likely to have insomnia than
      individuals with only one disorder. Insomnia is associated with poorer treatment
      outcomes for both PTSD and SUD, increased daytime symptomology for PTSD, and
      increased relapse for SUDs. As such, it is important to understand how sleep
      affects PTSD treatment among patients dually diagnosed with SUD and how sleep
      changes over time in a residential unit for SUDs. PARTICIPANTS: Participants were
      40 veterans with comorbid PTSD and SUD in a 28-day Substance Abuse Residential
      Rehabilitation Treatment Program (SARRTP) PTSD track. METHODS: Analyses used
      mixed models with Time (baseline, posttreatment, 3-month follow-up) to examine
      PTSD and insomnia severity over time. RESULTS: Results of the longitudinal mixed
      model showed that PTSD symptoms improved over time but that insomnia symptoms did
      not. Although baseline insomnia did not affect follow-up PTSD symptoms,
      individuals with greater insomnia severity at the start of treatment had more
      severe baseline PTSD symptomatology. However, there was not an interaction of
      insomnia and PTSD severity over time such that baseline insomnia did not affect
      PTSD trajectories. CONCLUSIONS: These findings are consistent with the PTSD
      outpatient treatment findings and further adds evidence that insomnia is
      unremitting without direct intervention. Given the relationship insomnia has with
      PTSD severity, SUD, and relapse, directly targeting insomnia may further help
      improve both PTSD and SUD treatment outcomes.

PMID- 29364694
TI  - Integrative Medicine and the Imperative for Health Justice.

PMID- 29364695
TI  - How neuropsychology can inform our understanding of preschool ADHD: Clinical and
      research implications.
AB  - Neuropsychological assessments in preschoolers have not received as much
      attention as in older children and adults. Attention-deficit/hyperactivity
      disorder (ADHD) is a common disorder that occurs in early childhood associated
      with poor academic and personal outcomes, such as learning and social
      difficulties. Preschoolers with ADHD may present cognitive deficits that are
      related with the ADHD symptoms of inattention, hyperactivity, and impulsivity,
      but may also interfere, beyond and above the ADHD symptoms, with everyday
      functioning. Most importantly, cognitive deficits in preschoolers seem to predict
      future ADHD symptoms. Yet, the practice of neuropsychological assessment in this
      age-group has been limited. The present selective review highlights the
      contribution of comprehensive neuropsychological assessments to the early
      identification of symptomatic preschoolers and to our understanding of the nature
      and developmental trajectory of ADHD.

PMID- 29364696
TI  - Implications of Cannabis Legalization on Youth and Young Adults.

PMID- 29364697
TI  - Maxillary expansion in an animal model with light, continuous force.
AB  - OBJECTIVES: Maxillary constriction is routinely addressed with rapid maxillary
      expansion (RME). However, the heavy forces delivered by most RME appliances to
      expand the palate may lead to deleterious effects on the teeth and supporting
      tissues. The objective of this study was to explore a more physiologic maxillary
      expansion with light continuous force. MATERIALS AND METHODS: Twenty 6-week-old
      Sprague-Dawley rats were equally divided into experimental (EXPT) and control
      (CTRL) groups. A custom-fabricated archwire expansion appliance made from 0.014
      inch copper-nickel-titanium wire was activated 5 mm and bonded to the maxillary
      molar segments of animals in the EXPT group for 21 days. The force applied to
      each maxillary segment was 5 cN. Microfocus x-ray computed tomography and
      histological analyses were used to compare the tooth movement and bone morphology
      in the midpalatal suture and buccal aspect of the alveolar process between the
      EXPT and CTRL groups. Descriptive statistics (mean +/- standard error of the
      mean) and nonparametric statistical tests were used to compare the outcomes
      across groups. RESULTS: Compared to the CTRL group, there was a statistically
      significant increase in buccal tooth movement and expansion of the midpalatal
      suture in the EXPT group. There was no difference in the bone morphologic
      parameters between groups. The mineral apposition rate was increased on the
      buccal surface of the alveolar process in the EXPT group. CONCLUSIONS:
      Application of light, continuous force resulted in maxillary osseous expansion
      due to bilateral sutural apposition and buccal drift of the alveolar processes.
      This animal experiment provides a more physiologic basis for maxillary expansion.

PMID- 29364698
TI  - Prevalence and Characterization of Staphylococcus aureus Strains in the Pork
      Chain Supply in Chile.
AB  - The detection of methicillin-resistant Staphylococcus aureus (MRSA) and other
      emerging strains in meat-producing animals and retail meat has increased the risk
      of contamination of food. The aim of this study was to determine the prevalence
      and characterize S. aureus strains isolated from the pork chain supply in Chile.
      A total of 487 samples were collected: 332 samples from pigs at farms and
      slaughterhouses (nasal, n = 155; skin, n = 177); 85 samples from carcasses at
      slaughterhouses; and 70 meat samples at supermarkets and retail stores. The
      isolation of S. aureus was carried out by selective enrichment and culture media.
      Biochemical testing (API(r) Staph) and PCR (detection of the nuc and mecA genes)
      were used to confirm S. aureus and MRSA strains. The agglutination test was used
      to determine the protein PBP2'. Enterotoxins (SEA, SEB, SEC, SED) were determined
      by agglutination test and the se genes by PCR method. Oxacillin and cefoxitin
      susceptibility testing were carried out using the diffusion method. The overall
      prevalence of S. aureus in the pork meat supply was 33.9%. A higher prevalence
      was detected on carcasses (56.5%), in pigs sampled at farms (40.6%) than in pigs
      sampled at slaughterhouses (23.3%) and in nonpackaged retail meat (43.1%) than
      packaged retail meat (5.3%) (p <= 0.05). No significant differences (p > 0.05)
      were found between the prevalence in pigs (28.3%) and pork meat (32.9%) and
      between natural pig farming (33.3%) and conventional production (52.8%). The mecA
      gene and the protein PBP2' were not detected in S. aureus strains. Two S. aureus
      strains exhibited oxacillin and cefoxitin resistance, and one S. aureus strain
      was resistant to cefoxitin. One S. aureus strain isolated from a meat sample was
      positive for enterotoxin SEB. Although the mecA gene was not detected, oxacillin
      resistant and seb-producing S. aureus strains were detected, which represent a
      risk in the pork chain supply.

PMID- 29364699
TI  - The Strength of Transosseous Medial Meniscal Root Repair Using a Simple Suture
      Technique Is Dependent on Suture Material and Position.
AB  - BACKGROUND: A simple suture technique in transosseous meniscal root repair can
      provide equivalent resistance to cyclic load and is less technically demanding to
      perform compared with more complex suture configurations, yet maximum yield loads
      are lower. Various suture materials have been investigated for repair, but it is
      currently not clear which material is optimal in terms of repair strength.
      Meniscal root anatomy is also complex; consisting of the ligamentous mid
      substance (root ligament), the transition zone between the meniscal body and root
      ligament; the relationship between suture location and maximum failure load has
      not been investigated in a simulated surgical repair. HYPOTHESES: (A) Using a
      knottable, 2-mm-wide, ultra-high-molecular-weight polyethylene (UHMWPE) braided
      tape for transosseous meniscal root repair with a simple suture technique will
      give rise to a higher maximum failure load than a repair made using No. 2 UHMWPE
      standard suture material for simple suture repair. (B) Suture position is an
      important factor in determining the maximum failure load. STUDY DESIGN:
      Controlled laboratory study. METHODS: In part A, the posterior root attachment of
      the medial meniscus was divided in 19 porcine knees. The tibias were potted, and
      repair of the medial meniscus posterior root was performed. A suture-passing
      device was used to place 2 simple sutures into the posterior root of the medial
      meniscus during a repair procedure that closely replicated single-tunnel,
      transosseous surgical repair commonly used in clinical practice. Ten tibias were
      randomized to repair with No. 2 suture (Suture group) and 9 tibias to repair with
      2-mm-wide knottable braided tape (Tape group). The repair strength was assessed
      by maximum failure load measured by use of a materials testing machine. Micro
      computed tomography (CT) scans were obtained to assess suture positions within
      the meniscus. The wide range of maximum failure load appeared related to suture
      position. In part B, 10 additional porcine knees were prepared. Five knees were
      randomized to the Suture group and 5 to the Tape group. All repairs were
      standardized for location, and the repair was placed in the body of the meniscus.
      A custom image registration routine was created to coregister all 29 menisci,
      which allowed the distribution of maximum failure load versus repair location to
      be visualized with a heat map. RESULTS: In part A, higher maximum failure load
      was found for the Tape group (mean, 86.7 N; 95% CI, 63.9-109.6 N) compared with
      the Suture group (mean, 57.2 N; 95% CI, 30.5-83.9 N). The 3D micro-CT analysis of
      suture position showed that the mean maximum failure load for repairs placed in
      the meniscus body (mean, 104 N; 95% CI, 81.2-128.0 N) was higher than for those
      placed in the root ligament (mean, 35.1 N; 95% CI, 15.7-54.5 N). In part B, the
      mean maximum failure load was significantly greater for the Tape group, 298.5 N (
      P = .016, Mann-Whitney U; 95% CI, 183.9-413.1 N), compared with that for the
      Suture group, 146.8 N (95% CI, 82.4-211.6 N). Visualization with the heat map
      revealed that small variations in repair location on the meniscus were associated
      with large differences in maximum failure load; moving the repair entry point by
      3 mm could reduce the failure load by 50%. CONCLUSION: The use of 2-mm braided
      tape provided higher maximum failure load than the use of a No. 2 suture. The
      position of the repair in the meniscus was also a highly significant factor in
      the properties of the constructs. CLINICAL RELEVANCE: The results provide insight
      into material and location for optimal repair strength.

PMID- 29364701
TI  - Novel regulator of vasopressin secretion: phoenixin.
AB  - The newly described hypothalamic peptide, phoenixin, is produced in the
      hypothalamus and adenohypophysis, where it acts to control reproductive hormone
      secretion. Both phoenixin and its receptor GPR173 are expressed in the
      hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, suggesting
      additional, nonreproductive effects of the peptide to control vasopressin (AVP)
      or oxytocin (OT) secretion. Hypothalamo-neurohypophysial explants released AVP
      but not OT in response to phoenixin. Intracerebroventricular administration of
      phoenixin into conscious, unrestrained male and female rats significantly
      increased circulating AVP, but not OT, levels in plasma, and it increased
      immediate early gene expression in the supraoptic nuclei of male rats. Bath
      application of phoenixin in hypothalamic slice preparations resulted in
      depolarization of PVN neurons, indicating a direct, neural action of phoenixin in
      the hypothalamus. Our results suggest that the newly described, hypothalamic
      peptide phoenixin, in addition to its effects on hypothalamic and pituitary
      mechanisms controlling reproduction, may contribute to the physiological
      mechanisms regulating fluid and electrolyte homeostasis.

PMID- 29364700
TI  - Angiotensin AT1A receptors expressed in vasopressin-producing cells of the
      supraoptic nucleus contribute to osmotic control of vasopressin.
AB  - Angiotensin II (ANG) stimulates the release of arginine vasopressin (AVP) from
      the neurohypophysis through activation of the AT1 receptor within the brain,
      although it remains unclear whether AT1 receptors expressed on AVP-expressing
      neurons directly mediate this control. We explored the hypothesis that ANG acts
      through AT1A receptors expressed directly on AVP-producing cells to regulate AVP
      secretion. In situ hybridization and transgenic mice demonstrated localization of
      AVP and AT1A mRNA in the supraoptic nucleus (SON) and the paraventricular nucleus
      (PVN), but coexpression of both AVP and AT1A mRNA was only observed in the SON.
      Mice harboring a conditional allele for the gene encoding the AT1A receptor
      (AT1Aflox) were then crossed with AVP-Cre mice to generate mice that lack AT1A in
      all cells that express the AVP gene (AT1AAVP-KO). AT1AAVP-KO mice exhibited
      spontaneously increased plasma and serum osmolality but no changes in fluid or
      salt-intake behaviors, hematocrit, or total body water. AT1AAVP-KO mice exhibited
      reduced AVP secretion (estimated by measurement of copeptin) in response to
      osmotic stimuli such as acute hypertonic saline loading and in response to
      chronic intracerebroventricular ANG infusion. However, the effects of these
      receptors on AVP release were masked by complex stimuli such as overnight
      dehydration and DOCA-salt treatment, which simultaneously induce osmotic,
      volemic, and pressor stresses. Collectively, these data support the expression of
      AT1A in AVP-producing cells of the SON but not the PVN, and a role for AT1A
      receptors in these cells in the osmotic regulation of AVP secretion.

PMID- 29364703
TI  - Care as Virtue, Care as Critical Frame: A Discussion of Four Recent
      Ethnographies.

PMID- 29364704
TI  - The Effect of Varying Atmospheric Pressure upon Habitability and Biosignatures of
      Earth-like Planets.
AB  - Understanding the possible climatic conditions on rocky extrasolar planets, and
      thereby their potential habitability, is one of the major subjects of exoplanet
      research. Determining how the climate, as well as potential atmospheric
      biosignatures, changes under different conditions is a key aspect when studying
      Earth-like exoplanets. One important property is the atmospheric mass, hence
      pressure and its influence on the climatic conditions. Therefore, the aim of the
      present study is to understand the influence of atmospheric mass on climate,
      hence habitability, and the spectral appearance of planets with Earth-like, that
      is, N2-O2 dominated, atmospheres orbiting the Sun at 1 AU. This work utilizes a
      1D coupled, cloud-free, climate-photochemical atmospheric column model; varies
      atmospheric surface pressure from 0.5 to 30 bar; and investigates temperature and
      key species profiles, as well as emission and brightness temperature spectra in a
      range between 2 and 20 MUm. Increasing the surface pressure up to 4 bar leads to
      an increase in the surface temperature due to increased greenhouse warming. Above
      this point, Rayleigh scattering dominates, and the surface temperature decreases,
      reaching surface temperatures below 273 K (approximately at ~34 bar surface
      pressure). For ozone, nitrous oxide, water, methane, and carbon dioxide, the
      spectral response either increases with surface temperature or pressure depending
      on the species. Masking effects occur, for example, for the bands of the
      biosignatures ozone and nitrous oxide by carbon dioxide, which could be visible
      in low carbon dioxide atmospheres. Key Words: Planetary habitability and
      biosignatures-Atmospheres-Radiative transfer. Astrobiology 18, 116-132.

PMID- 29364702
TI  - Synovial Fluid Profile at the Time of Anterior Cruciate Ligament Reconstruction
      and Its Association With Cartilage Matrix Composition 3 Years After Surgery.
AB  - BACKGROUND: Anterior cruciate ligament tears can lead to posttraumatic
      osteoarthritis. In addition to biomechanical factors, changes in biochemical
      profiles within the knee joint after injury and anterior cruciate ligament
      reconstruction (ACLR) may play a role in accelerating joint degeneration.
      Hypothesis/Purpose: It was hypothesized that cartilage matrix composition after
      ACLR is associated with the degree of inflammatory response after initial injury.
      This study evaluated the association between the inflammatory response after
      injury-as indicated by cytokine, metalloproteinase, and cartilage degradation
      marker concentrations in synovial fluid-and articular cartilage degeneration,
      measured by T1rho and T2 quantitative magnetic resonance imaging up to 3 years
      after ACLR. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Twenty-six
      subjects from a longitudinal cohort study who underwent ACLR at a mean 8.5 weeks
      after injury (range, 4-19 weeks) had synovial fluid aspirated at the time of
      surgery. Immunoassays quantified biomarkers in synovial fluid. T1rho and T2
      values of articular cartilage were calculated with magnetic resonance scans
      acquired prior to surgery and at 6 months and 1, 2, and 3 years after surgery.
      Pearson correlation coefficients were calculated among the various biomarkers. K
      means clustering was used to group subjects with similar biomarker profiles.
      Generalized estimating equations were used to find the overall differences in
      T1rho and T2 values throughout these first 3 years after surgery between the
      clusters while controlling for other factors. RESULTS: Significant and strong
      correlations were observed between several cytokines (interleukin 6 [IL-6], IL-8,
      IL-10, and tumor necrosis factor alpha) and 2 matrix metalloproteinases (MMP-1
      and MMP-3) ( P < .05). Moderate correlations were found among combinations of C
      terminal crosslinked telopeptide type II collagen, N-terminal telopeptide,
      cartilage oligomeric matrix protein, and sulfated glycosaminoglycan ( P < .05).
      Two clusters were generated, 1 of which was characterized by lower concentrations
      of cytokines (IL-6, IL-8, IL-10, tumor necrosis factor alpha) and MMP-1 and MMP-3
      and higher sulfated glycosaminoglycan. This cluster was associated with
      significantly higher T1rho and T2 values in the medial tibial and patellar
      cartilage over the first 3 years after ACLR. CONCLUSION: At the time of ACLR
      surgery, profiles of synovial fluid inflammatory cytokines, degradative enzymes,
      and cartilage breakdown products show promise as predictors of abnormal cartilage
      tissue integrity (increased T1rho and T2 values) throughout the first 3 years
      after surgery. CLINICAL RELEVANCE: The results suggest an intricate relationship
      between inflammation and cartilage turnover, which can in turn be influenced by
      timing after injury and patient factors.

PMID- 29364705
TI  - miR-654-5p Targets GRAP to Promote Proliferation, Metastasis, and Chemoresistance
      of Oral Squamous Cell Carcinoma Through Ras/MAPK Signaling.
AB  - Oral squamous cell carcinoma (OSCC) is characterized by rapid local migration and
      invasion. This study was aimed at clarifying the effect of miR-654-5p on
      progression of OSCC. miR-654-5p promoted proliferation, metastasis, and
      chemoresistance of OSCC in vitro and in vivo. Consistently, miR-654-5p was
      upregulated in late-stage OSCC and was correlated with poor prognosis of OSCC
      patients. Furthermore, miR-654-5p was mechanistically verified to target Grb-2
      related adaptor protein (GRAP), accompanied by the activation of Ras/MAPK
      signaling and the facilitation of epithelial-mesenchymal transition in OSCC
      cells. GRAP was downregulated in T1-2 stage versus T3-4 stage head and neck
      squamous cell carcinoma (HNSC) and was negatively correlated with tumor-node
      metastases (TNM) stage in HNSC patients based on The Cancer Genome Atlas (TCGA)
      analysis. In addition, GRAP was positively correlated with good prognosis in HNSC
      patients. Our findings suggest that the miR-654-5p/GRAP/Ras/Erk signaling pathway
      in OSCC cells might contribute to the underlying mechanism through which miR-654
      5p participates in the regulation of OSCC progression. miR-654-5p, as a potential
      biomarker for the clinical diagnosis and prognosis of OSCC, may be an effective
      anticancer target for the treatment of OSCC.

PMID- 29364706
TI  - Influence of a Character-Based App on Children's Learning of Nutritional
      Information: Should Apps Be Served with a Side of Media Characters?
AB  - OBJECTIVE: Childhood obesity is a health issue in the United States, associated
      with marketing practices in which media characters are often used to sell
      unhealthy products. This study examined exposure to a socially contingent touch
      screen gaming app, which replied immediately, reliably, and accurately to
      children's actions. Children's recall of nutritional content and their liking of
      the character were assessed. MATERIALS AND METHODS: Four- and five-year-old
      children (N = 114) received no-exposure, single-exposure, or repeated-exposure to
      a character-based iPad app rewarding healthy and penalizing unhealthy behaviors.
      Children reported how much they liked the character and recalled healthy and
      unhealthy items from the app. An ordinary least squares regression was conducted
      on how much children liked the character by condition. Poisson regressions were
      conducted on the number of items recalled by condition alone, and in an
      interacted model of treatment condition by liking the character. RESULTS:
      Children liked the character more in the repeated app-exposure condition than in
      the control group (P = 0.018). Children in the repeated and single app-exposure
      conditions recalled more healthy (P < 0.001) and unhealthy (P < 0.001) items than
      the control group. Within treatment conditions, liking the character increased
      recall of healthy items in the single app-exposure compared to the repeated app
      exposure condition (P = 0.005). CONCLUSIONS: Results revealed that repeated
      exposure increased children's learning of nutritional information and liking of
      the character. The results contribute to our understanding of how to deliver
      effective nutrition information to young children in a new venue, a gaming app.

PMID- 29364707
TI  - Electrochemical Sensor Arrays.
AB  - The importance of sensor arrays in environmental, food and clinical analysis is
      discussed. The possible designs of sensor arrays is shown. The most reliable
      mathematical models for data processing are presented. The importance of
      different types of electrochemical sensor arrays in analytical chemistry as well
      as their performances are shown.

PMID- 29364708
TI  - Preconcentration of platinum group metals for their determination in
      environmental samples.
AB  - This article has no abstract.

PMID- 29364709
TI  - The Proper Place of Analytical Chemistry in Environmental Management.
AB  - Obtaining new information through characterizaton (chemical analysis) has its
      costs associated with it. These costs must be justified. It is argued that the
      value of any analysis, new chemical sensor, or a new analytical procedure for
      environmental management task is ultimately determined by its rational use. A
      formal procedure for justification of chemical characterization is outlined.

PMID- 29364710
TI  - Occupational needs and priorities of women experiencing homelessness: Les besoins
      et priorites occupationnels des femmes en situation d'itinerance.
AB  - BACKGROUND: Women in unstable housing or who are homeless experience disruptions
      of occupational engagement and performance. Little is known about their
      perspective on their occupational needs and priorities. PURPOSE: This study aimed
      to determine how patterns of occupational engagement and performance are
      facilitated or hindered by personal factors and resources available to sheltered
      women. METHOD: A participatory, descriptive mixed-methods study design was used.
      Twenty-one residents were interviewed using the Canadian Occupational Performance
      Measure, the Goal Attainment Scale, and a time-use inventory. Nineteen residents
      participated in semistructured qualitative interviews. Qualitative data were
      analysed using interpretive description. FINDINGS: Participants spent most time
      on sleep and passive leisure and identified occupational performance issues and
      goals related to active leisure and employment. Participants' occupational lives
      were described as transitional journeys comprising five subthemes: seeking safety
      and stability, being sheltered, shaping one's identity, developing resilience,
      and engaging in contemplation, contribution, and connectedness through
      occupation. IMPLICATIONS: Trauma-informed and strengths-based approaches are
      recommended for this population. Future research should study the implementation
      of occupation-based interventions in community settings.

PMID- 29364712
TI  - The Daily Experiences of Pleasure, Productivity, and Restoration Profile: A case
      study: Etude de cas sur l'utilite du Daily Experiences of Pleasure, Productivity,
      and Restoration Profile.
AB  - BACKGROUND: Occupational therapy enables clients to self-manage their health
      through the use of occupation; however, additional occupation-focused assessments
      are needed to capture people's subjective experiences associated with everyday
      activities as awareness of one's experiences can help promote change. PURPOSE:
      This qualitative case study explored the utility of one such assessment, the
      Daily Experiences of Pleasure, Productivity, and Restoration Profile (PPR
      Profile). METHOD: Five spousal caregivers completed and discussed the PPR Profile
      with an occupational therapist. Interviews with the caregivers and therapist
      occurred during and following use. Content analysis revealed several themes.
      FINDINGS: Both caregivers and the occupational therapist reported that use of the
      PPR Profile provided benefits but not without challenges. IMPLICATIONS: The
      findings support preliminary utility of the PPR Profile; however, additional
      research is needed and occupational therapists need to be aware of the challenges
      when deciding to use the tool.

PMID- 29364713
TI  - Favoriser la diffusion de la recherche dans diverses langues et cultures:
      Travailler au-dela des modeles occidentaux et anglocentriques.

PMID- 29364714
TI  - Opportunities for well-being: The right to occupational engagement.
AB  - BACKGROUND: The Canadian Association of Occupational Therapists' 2017 conference
      theme prompted thoughts about shaping our profession's future. PURPOSE: This
      Muriel Driver Memorial Lecture explores how occupational therapy's future might
      be shaped to become more important, relevant, and valuable to society. KEY
      ISSUES: Because occupational engagement is integral to human well-being and
      because well-being is integral to human rights, occupational therapy could
      usefully advance the right of all people to engage in occupations that contribute
      positively to their own well-being and the well-being of their communities.
      IMPLICATIONS: Occupational therapy's importance to society will be manifested
      when we focus unambiguously on well-being; extend our efforts beyond enhancing
      the abilities of individuals whose lives are already impacted by illness, injury,
      or impairment; and address the opportunities for achieving well-being through
      occupational engagement of all those whose capabilities-their opportunities to do
      what they have the abilities to do-are inequitably constrained.

PMID- 29364715
TI  - ?

PMID- 29364717
TI  - Supporting research dissemination across languages and cultures: Working beyond
      Western and Anglocentric lines.

PMID- 29364719
TI  - Experiences of women aging with the human immunodeficiency virus: A qualitative
      study: Experiences vecues par des femmes vieillissant avec le virus de
      l'immunodeficience humaine : etude qualitative.
AB  - BACKGROUND: While the literature on HIV and aging has grown significantly in the
      past decade, there has been little examination of the needs of older women living
      with HIV and their disability experiences. PURPOSE: The purpose of this study was
      to uncover the experiences of aging with HIV from the perspective of older women.
      METHOD: An interpretive qualitative study was undertaken using semistructured
      interviews to explore the experiences of 10 women who are HIV positive between
      the ages of 51 and 62 years. Interview transcripts were analyzed thematically.
      FINDINGS: Data analysis revealed seven themes: varying levels of acceptance,
      battling stigma of disclosure, declining functionality, living with negative
      emotions, practising healthy lifestyles, seeking social supports, and maximizing
      support from community services. IMPLICATIONS: There is a need for women's peer
      support groups, education for women with HIV and their families, and enhanced
      support services. Suggestions are provided for how occupational therapists can
      enable participation.

PMID- 29364721
TI  - Usefulness of Testicular Volume, Apparent Diffusion Coefficient, and Normalized
      Apparent Diffusion Coefficient in the MRI Evaluation of Infertile Men With
      Azoospermia.
AB  - OBJECTIVE: The purpose of this article is to assess retrospectively the
      usefulness of testicular volume, apparent diffusion coefficient (ADC), and
      normalized ADC as measured using MRI in predicting the histopathologic grade of
      azoospermia and in differentiating obstructive from nonobstructive azoospermia.
      MATERIALS AND METHODS: A computerized search generated a list of 30 infertile men
      with azoospermia who had undergone both scrotal MRI and testis biopsy. MRI
      determined testicular volumes, ADCs, and normalized ADCs were compared between
      infertile men with obstructive azoospermia and those with nonobstructive
      azoospermia. The normalized ADC was calculated as ADC of the testis divided by
      the ADC of the bladder lumen. RESULTS: Sixteen men had obstructive azoospermia
      and 14 had nonobstructive azoospermia. The testicular volume was significantly
      greater in patients with obstructive azoospermia (8.7-27.6 mL) than in patients
      with nonobstructive azoospermia (1.8-15.4 mL; p < 0.001). The ROC AUC for
      distinguishing nonobstructive from obstructive azoospermia using testicular
      volume was 0.92 (a cutoff value of <= 13.06 mL yielded sensitivity of 85.71% and
      specificity of 87.5%). Testicular ADC and normalized ADC were significantly lower
      in patients with obstructive azoospermia (0.329 * 10-3 to 1.578 * 10-3 mm2/s for
      ADC; 0.113 to 0.449 for normalized ADC) than in patients with nonobstructive
      azoospermia (0.801 * 10-3 to 2.211 * 10-3 mm2/s [p = 0.0094] for ADC; 0.235 to
      0.61 [p = 0.0001] for normalized ADC). The ROC AUCs for distinguishing
      nonobstructive from obstructive azoospermia using testicular ADC and normalized
      ADC were 0.741 (a cutoff value of > 1.031 * 10-3 mm2/s yielded sensitivity of
      92.86% and specificity of 56.25%) and 0.875 (a cutoff value of > 0.425 yielded
      sensitivity of 78.57% and specificity of 93.75%), respectively. CONCLUSION:
      Testicular volume, ADC, and normalized ADC, as measured using MRI, are useful in
      predicting the histopathologic grade of azoospermia and in differentiating
      obstructive from nonobstructive azoospermia.

PMID- 29364720
TI  - Testing Syndromes of Psychopathology in Parent and Youth Ratings Across
      Societies.
AB  - As societies become increasingly diverse, mental health professionals need
      instruments for assessing emotional, behavioral, and social problems in terms of
      constructs that are supported within and across societies. Building on decades of
      research findings, multisample alignment confirmatory factor analyses tested an
      empirically based 8-syndrome model on parent ratings across 30 societies and
      youth self-ratings across 19 societies. The Child Behavior Checklist for Ages 6
      18 and Youth Self-Report for Ages 11-18 were used to measure syndromes
      descriptively designated as Anxious/Depressed, Withdrawn/Depressed, Somatic
      Complaints, Social Problems, Thought Problems, Attention Problems, Rule-Breaking
      Behavior, and Aggressive Behavior. For both parent ratings (N = 61,703) and self
      ratings (N = 29,486), results supported aggregation of problem items into 8 first
      order syndromes for all societies (configural invariance), plus the invariance of
      item loadings (metric invariance) across the majority of societies. Supported
      across many societies in both parent and self-ratings, the 8 syndromes offer a
      parsimonious phenotypic taxonomy with clearly operationalized assessment
      criteria. Mental health professionals in many societies can use the 8 syndromes
      to assess children and youths for clinical, training, and scientific purposes.

PMID- 29364722
TI  - Low-Dose CT for Evaluation of Suspected Urolithiasis: Diagnostic Yield for
      Assessment of Alternative Diagnoses.
AB  - OBJECTIVE: The purpose of this study is to assess the diagnostic yield of low
      dose (LD) CT for alternative diagnoses in patients with suspected urolithiasis.
      MATERIALS AND METHODS: In this retrospective study, we included 776 consecutive
      patients who underwent unenhanced abdominal CT for evaluation of suspected
      urolithiasis. All examinations were performed with an LD CT protocol; images were
      reconstructed using iterative reconstruction. The leading LD CT diagnosis was
      recorded for each patient and compared with the final clinical diagnosis, which
      served as the reference standard. RESULTS: The mean (+/- SD) effective dose of CT
      was 1.9 +/- 0.6 mSv. The frequency of urolithiasis was 82.5% (640/776). LD CT
      reached a sensitivity of 94.1% (602/640), a specificity of 100.0% (136/136), and
      an accuracy of 95.1% (738/776) for the detection of urolithiasis. In 93 of 136
      patients (68.4%) without urolithiasis, alternative diagnoses were established as
      the final clinical diagnoses. Alternative diagnoses were most commonly located in
      the genitourinary (n = 53) and gastrointestinal (n = 18) tracts. LD CT correctly
      provided alternative diagnoses for 57 patients (61.3%) and was false-negative for
      five patients (5.4%). The most common clinical alternative diagnoses were urinary
      tract infections (n = 22). Seven diagnoses missed at LD CT were located outside
      the FOV. For 43 of all 776 patients (5.5%), neither LD CT nor clinical workup
      could establish a final diagnosis. The sensitivity, specificity, and accuracy of
      LD CT for the detection of alternative diagnoses were 91.9% (57/62), 95.6%
      (43/45), and 93.5% (100/107), respectively. CONCLUSION: LD CT enables the
      diagnosis of most alternative diagnoses in the setting of suspected urolithiasis.
      The most frequent alternative diagnoses missed by LD CT are urinary tract
      infections or diagnoses located outside the FOV of the abdominopelvic CT scan.

PMID- 29364723
TI  - Ultrasound Guidance Versus CT Guidance for Peripheral Lung Biopsy: Performance
      According to Lesion Size and Pleural Contact.
AB  - OBJECTIVE: The purpose of this study was to compare efficacy and safety of biopsy
      guided by ultrasound (US) versus CT for lung lesions with pleural contact.
      MATERIALS AND METHODS: Among 1269 image-guided thoracic biopsies obtained at our
      institution between 2004 and 2016, 150 were US-guided for lung lesions with
      pleural contact (78 men, 72 women; mean age, 67 years). Of those, 94 were
      performed using US only; 56 had initial CT localization. A comparison cohort of
      100 consecutive CT-guided biopsies for lung lesions with pleural contact was
      identified (60 men, 40 women; mean age, 65 years). Biopsy type, number of passes,
      sample adequacy, final pathologic results, complications, procedural time, lesion
      diameter, and pleural contact were recorded. Fisher exact and t tests were used
      for statistical analysis. RESULTS: US-guided biopsy was associated with fewer
      complications (7%) than CT-guided procedures (24%; p < 0.001). Mean procedure
      times (+/- SD) were shorter with US only (31 +/- 16 min) than with CT only (45 +/
      26 min; p < 0.001) or US with CT localization (45 +/- 18 min; p < 0.001).
      Procedural times were longer for patients with small lesions and those with
      lesser pleural contact. Sample adequacy was best when core biopsy was performed
      with US and CT. Fewer passes were performed with US guidance than with CT
      guidance (mean, 3.1 +/- 1.8 vs 4.4 +/- 1.9, respectively, p < 0.001), with a
      trend toward improved pathologic adequacy (98% vs 93%, respectively, p = 0.122).
      Subgroup analysis showed fewer complications for lesions 31-50 mm (p = 0.029),
      improved sample adequacy for lesions 10-30 mm (p = 0.0032), and shorter
      procedural times for lesions 10-30 mm (p = 0.0001) with US than with CT.
      CONCLUSION: US guidance should be considered for biopsy of peripheral lung and
      pleural lesions larger than 10 mm, because it is safer, faster, and possibly more
      accurate than CT guidance.

PMID- 29364724
TI  - Trends and Variation in the Utilization and Diagnostic Yield of Chest Imaging for
      Medicare Patients With Suspected Pulmonary Embolism in the Emergency Department.
AB  - OBJECTIVE: The purpose of this study is to assess trends and variation in chest
      CT utilization in the emergency department (ED) and its diagnostic yield for
      suspected pulmonary embolism (PE) among a national sample of Medicare
      beneficiaries. The relationship between hospital and provider characteristics is
      also discussed. MATERIALS AND METHODS: We conducted an observational analysis of
      Medicare beneficiaries evaluated in the ED for suspected PE from 2000 to 2009.
      Standard Medicare analytic files representing a 20% sample of fee-for-service
      beneficiaries were linked to the American Hospital Association Annual Survey of
      Hospitals, American Medical Association Physician Masterfile, Medicare Physician
      Identification and Eligibility Registry, and Dartmouth Atlas Project to calculate
      geographic- and physician-level chest CT utilization (i.e., the proportion of ED
      visits involving chest CT examination for suspected PE) and diagnostic yield
      (i.e., the proportion of chest CT examinations with a positive PE diagnosis).
      RESULTS: Of 2.5 million ED visits, 2.5% (n = 164,274) included chest CT for
      suspected PE; 6.2% visits (n = 10,121) resulted in positive findings for PE.
      Between 2000 and 2009, chest CT utilization increased fivefold. Geographic
      variation in CT utilization (median, 2.38%; interquartile range [IQR], 1.91
      2.92%) and diagnostic yield (median, 6.31%; IQR, 5.11-7.66%) was observed between
      306 hospital referral regions. Physician use of imaging was explained by greater
      experience (lower utilization and higher yield) and emergency medicine board
      certification (lower utilization and equivalent yield). CONCLUSION: CT
      utilization in the ED for suspected PE has steadily risen, whereas diagnostic
      yields have declined over time. Wide variation in practice is observed at the
      physician and geographic levels and is explained by several physician and
      hospital characteristics. Taken together, our findings suggest a substantial
      inefficiency of chest CT use and substantial opportunities for improvement.

PMID- 29364726
TI  - Impact of Interventional Oncology Therapies on Tumor Microenvironment and
      Strategies to Enhance Their Efficacy.
AB  - OBJECTIVE: We provide a brief review of the tumor microenvironment, the impact of
      six interventional radiology treatments on the tumor microenvironment, and
      potential methods to improve treatment efficacy. CONCLUSION: Interventional
      oncology plays a unique role in cancer therapy, contributing to both
      antitumorigenic and protumorigenic effects.

PMID- 29364725
TI  - Progressive Sarcopenia in Patients With Colorectal Cancer Predicts Survival.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      sarcopenia and overall and progression-free survival in patients with colorectal
      cancer. MATERIALS AND METHODS: This study was retrospective and complied with
      HIPAA. Patients with colorectal cancer who underwent CT at the time of and 6-18
      months after diagnosis were included. Patients were followed for at least 5 years
      after diagnosis. Skeletal muscle index (SMI) and mean muscle attenuation of the
      psoas and paraspinal muscles at the L4 level determined the degree of sarcopenia.
      Composite measurements combining psoas and paraspinal muscles (total muscle) were
      also obtained. Univariate and multivariate Cox proportional hazard analysis was
      performed to evaluate the association between survival and changes in SMI and
      changes in attenuation. Kaplan-Meier analysis was also performed. RESULTS: A
      total of 101 patients were included (mean age +/- SD, 63.7 +/- 13.7 years; 68
      men, 33 women). The hazard ratios for overall survival were 2.27, 1.68, and 1.54
      for changes in SMI of the psoas muscle, paraspinal muscle, and total muscle (all
      p < 0.05). The hazard ratios for overall survival were 1.14, 1.18, and 1.24 for
      changes in attenuation of the psoas muscle, paraspinal muscle, and total muscle,
      respectively (all p < 0.05). The hazard ratios for progression-free survival were
      1.33, 1.41, and 1.23 for changes in SMI of the psoas muscle, paraspinal muscle,
      and total muscle (not statistically significant). The hazard ratios for
      progression-free survival were 1.10, 1.21, and 1.23 for changes in attenuation of
      the psoas muscle, paraspinal muscle, and total muscle, respectively (p < 0.05).
      Kaplan-Meier analysis showed significant differences in overall and progression
      free survival based on sex-specific quartiles of muscle quantity and quality.
      CONCLUSION: Progressive sarcopenia after diagnosis of colorectal cancer has a
      significant negative prognostic association with overall and progression-free
      survival.

PMID- 29364728
TI  - Development of Surgical Management in Primary Rhegmatogenous Retinal Detachment
      Treatment from 2009 to 2015.
AB  - PURPOSE: To evaluate the evolution of surgical methods over a 7-year period in
      patients with primary rhegmatogenous retinal detachment (RRD) and its relation to
      functional outcome and intra- and postoperative complications. METHODS: This
      prospective observational study included 628 patients with primary RRD who
      underwent surgical repair between January 2009 and December 2015. The main
      outcome measures were the type of surgical procedure ((scleral buckle (SB), pars
      plana vitrectomy (PPV), combination of SB and PPV or cryocoagulation (CC)) and
      intraocular tamponades. In addition, functional outcome and intra/postoperative
      complications were assessed over the observational period. RESULTS: During the 7
      year observation, the percent of SB procedures decreased from 40.5% in 2009 to
      2.7% in 2014, while PPV increased from 38% in 2009 to above 90% in 2014. In 2015,
      the SB procedure was performed in 10.3% and PPV in 85.6% of patients with RRD (p
      < 0.001). No consistent trend was observed for the use of intraocular gas
      tamponade. The functional outcome within the 7-year observation ranged from 0.25
      +/- 0.31logmar in 2012 to 0.42 +/- 0.40logmar in 2009 and showed no statistically
      significant trend (p = 0.28). Intraoperative complications did not change between
      2009 and 2015. The rate of cataract surgery and epiretinal membrane development
      did not change (p = 0.27; p = 0.09). The percent of re-detachment ranged from 6.2
      to 16.5% within the observational period (p = 0.14). CONCLUSION: A shift toward
      PPV alone for primary RRD repair was observed during the 7-year observation. No
      decrease in functional outcome or increase of intra- and postoperative
      complications or decrease of primary and final anatomic success rate was observed
      following the change in surgical procedure.

PMID- 29364729
TI  - Parent Expectancies and Preferences for Mental Health Treatment: The Roles of
      Emotion Mind-Sets and Views of Failure.
AB  - Because parents are primary gatekeepers to mental health care for their children,
      parental expectations that mental health treatment is ineffective may undermine
      treatment seeking, retention, and response. Thus, a need exists to understand
      parents' expectations about treatment and to develop scalable interventions that
      can instill more favorable views. We examined parents' treatment expectancies and
      preferences for their offspring and themselves in relation to two global beliefs:
      mind-sets (malleability beliefs) of emotions and anxiety, and views of failure as
      enhancing versus debilitating. Study 1 (N = 200; 49.5% fathers; 70.4% Caucasian)
      examined associations among parents' emotion mind-sets, anxiety mind-sets,
      failure beliefs, and treatment expectancies and preferences. Study 2 (N = 430;
      44.70% fathers; 75.80% Caucasian) tested whether online inductions teaching
      "growth emotion mind-sets" (viewing emotions as malleable), adaptive failure
      beliefs, or both improved parents' treatment expectancies and hypothetical
      preferences for treatment (vs. no-treatment). Participants received one of three
      8- to 15-min inductions or a psychoeducation control, rating treatment
      expectancies. and preferences pre- and postinduction. In Study 1, fixed emotion
      mind-sets and failure-is-debilitating beliefs were associated with lower parent
      psychotherapy expectancies for offspring and themselves and stronger "no
      treatment" preferences for offspring. In Study 2, inductions teaching (a) growth
      emotion mind-sets only and (b) growth emotion mind-sets and failure-is-enhancing
      beliefs improved parents' psychotherapy expectancies for themselves (ds = .38,
      .51) and offspring (ds = .30, .43). No induction increased parents' hypothetical
      preferences for treatment (vs. no-treatment). Findings suggest scalable
      strategies for strengthening parents' psychotherapy effectiveness beliefs for
      themselves and their children.

PMID- 29364730
TI  - Improving Prehospital Protocol Adherence Using Bundled Educational Interventions.
AB  - BACKGROUND: Seizures and anaphylaxis are life-threatening conditions that require
      immediate treatment in the prehospital setting. There is variation in treatment
      of pediatric prehospital patients for both anaphylaxis and seizures. This
      educational study was done to improve compliance with pediatric prehospital
      protocols, educate prehospital providers and decrease variation in care.
      OBJECTIVE: To improve the quality of care for children with seizures and
      anaphylaxis in the prehospital setting using a bundled, multifaceted educational
      intervention. METHODS: Evidence-based pediatric prehospital guidelines for
      seizures and anaphylaxis were used to create a curriculum for the paramedics in
      the EMS system. The curriculum included in-person training, videos, distribution
      of decision support tools, and a targeted social media campaign to reinforce the
      evidence-based guidelines. Prehospital charts were reviewed for pediatric
      patients with a chief complaint of anaphylaxis or seizures who were transported
      by paramedics to one of ten hospitals, including three children's hospitals, for
      8 months prior to the intervention and eight months following the intervention.
      The primary outcome for seizures was whether midazolam was given via the
      preferred intranasal (IN) or intramuscular (IM) routes. The primary outcome for
      anaphylaxis was whether IM epinephrine was given. RESULTS: A total of 1,402
      pediatric patients were transported for seizures by paramedics to during the
      study period. A total of 88 patients were actively seizing pre-intervention and
      93 post-intervention. Of the actively seizing patients, 52 were given midazolam
      pre-intervention and 62 were given midazolam post-intervention. Pre-intervention,
      29% (15/52) of the seizing patients received midazolam via the preferred IM or IN
      routes, compared to 74% (46/62) of the seizing patients post-intervention. A
      total of 45 patients with anaphylaxis were transported by paramedics, 30 pre
      intervention and 15 post-intervention. Paramedics administered epinephrine to 17%
      (5/30) patients pre-intervention and 67% (10/15) patients post-intervention.
      CONCLUSION: The use of a bundled, multifaceted educational intervention including
      in-person training, decision support tools, and social media improved adherence
      to updated evidence-based pediatric prehospital protocols.

PMID- 29364731
TI  - YC-1 Inhibits VEGF and Inflammatory Mediators Expression on Experimental Central
      Retinal Vein Occlusion in Rhesus Monkey.
AB  - PURPOSES: To investigate the therapeutic potential of YC-1 for experimental
      central retinal vein occlusion (CRVO) of rhesus monkey. METHODS: Six adult rhesus
      monkeys were recruited in this study. Laser-induced CRVO was established in both
      eyes of all subjects. Intravitreal injection of YC-1 90 MUl (200 MUM with 0.01%
      dimethyl sulfoxide (DMSO) as vehicle) was administrated in right eye and 0.01%
      DMSO 90 MUl in left eye respectively at 1 week after CRVO established. All eyes
      underwent routine examination at 1 day, 1 week, 2 week, and 1 month after
      intravitreal injection of YC-1 or DMSO. Meanwhile, vitreous fluid was collected
      at each time points to analyze concentration of VEGF, HIF-1alpha, IL-6, IL-8, and
      MCP-1 mediators by CBA or ELASA method. RESULTS: The experimental CRVO was
      successfully established in six rhesus monkeys. As expected, the thickness of
      macular edema significantly decreased at 1 week and 2 weeks after YC-1 injection
      compared with that of DMSO injection. Subsequently, the central macular thickness
      in all eyes was recovered to the initial levels at 1 month after
      photocoagulation. Intraocular pressure (IOP) was not significantly different
      between two groups during all follow up. Meanwhile, the concentration of IL-6, IL
      8, VEGF, and HIF-1alpha in vitreous fluid significantly decreased after YC-1
      injection compared with that of DMSO injection, MCP-1 was not significantly
      different between both groups. CONCLUSIONS: Intravitreal injection of YC-1
      significantly alleviated macular edema compared with that of DMSO control group.
      Meanwhile, both inflammatory factors and angiogenesis-related factors expression
      were inhibited in vitreous by YC-1 injection.

PMID- 29364732
TI  - Improving Practice Guideline Adherence Through Peer Feedback: Impact of an
      Ambulatory Cardiology Curriculum.
AB  - PROBLEM: Graduate medical trainees must be prepared to practice in a quality
      driven system that values adherence to and documentation of evidence-based care.
      Few validated approaches exist to teach these skills. Our objective was to
      develop, implement, and evaluate an ambulatory practice improvement curriculum
      capitalizing on peer feedback aimed at improving cardiology fellow guideline
      knowledge, adherence, and chart documentation. INTERVENTION: Four outpatient
      topics were reviewed in dedicated 1-hour sessions: stable ischemic heart disease,
      heart failure, atrial fibrillation, and aortic valvular disease. Each session
      began with peer review, critique, and guideline adherence discussion of
      deidentified outpatient fellow clinic charts, followed by discussion of clinical
      guidelines. The open discussion of real clinic notes provided a forum for peer
      feedback exchange. Before each session and after the final session, participants
      completed a multiple-choice knowledge assessment and self-assessment of comfort
      with the guidelines. To evaluate the potential effect on patient care, random
      clinic chart audits were conducted before and after the curriculum using a chart
      scoring system. CONTEXT: Although the format is broadly applicable, the specific
      curriculum content was designed for a cardiology fellowship cohort in a large
      academic medical center. It was organized and implemented by 2 cardiology fellows
      under the direction and supervision of program directors. The curriculum was
      implemented during prescheduled noon conference hours. The intention was to carry
      forward this ambulatory curriculum in subsequent years and to use the first 4
      sessions to study its potential successes and opportunities for improvement.
      OUTCOME: All 22 general cardiology fellows attended at least two sessions (M =
      3.1). Knowledge test scores rose from 52.6% to 73.0% (20.4% increase, p < .001),
      95% confidence interval (CI) [13.6%, 27.2%]. Self-reported guidelines knowledge
      improved by 15.1% (p = .002), 95% CI [6.2%, 24.0%], and self-reported
      documentation improved by 12.5% (p = .008), 95% CI [3.8%, 21.7%]. Chart audit
      scores improved by 17.8% (p < .001), 95% CI [10.6%, 25.0%], driven in part by
      16.4% improvement in adherence to Class I therapies (p = .001). LESSONS LEARNED:
      A targeted curriculum combining peer chart review, feedback, and guideline
      discussion was associated with significant improvement in fellows' knowledge and
      adherence to evidence-based therapies. Peer assessment and group-based education
      and feedback can be leveraged to improve trainee education and impact patient
      care.

PMID- 29364733
TI  - Feasibility and reliability of a virtual reality oculus platform to measure
      sensory integration for postural control in young adults.
AB  - BACKGROUND: Using Unity for the Oculus Development-Kit 2, we have developed an
      affordable, portable virtual reality platform that targets the visuomotor domain,
      a missing link in current clinical assessments of postural control. Here, we
      describe the design and technical development as well as report its feasibility
      with regards to cybersickness and test-retest reliability in healthy young
      adults. METHOD: Our virtual reality paradigm includes two functional scenes
      ('City' and 'Park') and four moving dots scenes. Twenty-one healthy young adults
      were tested twice, one to two weeks apart. They completed a simulator sickness
      questionnaire several times per session. Their postural sway response was
      recorded from a forceplate underneath their feet while standing on the floor,
      stability trainers, or a Both Sides Up (BOSU) ball. Sample entropy, postural
      displacement, velocity, and excursion were calculated and compared between
      sessions given the visual and surface conditions. RESULTS: Participants reported
      slight-to-moderate transient side effects. Intra-Class Correlation values mostly
      ranged from 0.5 to 0.7 for displacement and velocity, were above 0.5 (stability
      trainer conditions) and above 0.4 (floor mediolateral conditions) for sample
      entropy, and minimal for excursion. CONCLUSION: Our novel portable VR platform
      was found to be feasible and reliable in healthy young adults.

PMID- 29364734
TI  - A Moderated Mediation Model of the Relationship between Media, Social Capital,
      and Cancer Knowledge.
AB  - We combined insights from various theories and models of media learning, and
      advanced an indirect model accounting for the mechanisms underlying the media
      influences on knowledge acquisition. Our model was largely supported by the data
      from a two-wave longitudinal panel survey with a nationwide sample of Korean
      adults. It was found that both personal cancer history and cancer worry were
      positively associated with exposure to stomach cancer information from the media.
      In turn, exposure to media information was positively related to reflective
      integration of that information, which ultimately leads to stomach cancer
      knowledge only among people with high levels of social capital. These findings
      suggest that media uses and effects are not only an individual but also a
      contextually dependent experience.

PMID- 29364735
TI  - EMS Physician-Performed Clinical Interventions in the Field.

PMID- 29364736
TI  - Medicaid Versus Marketplace Coverage For Near-Poor Adults: Effects On Out-Of
      Pocket Spending And Coverage.
AB  - In states that expanded Medicaid eligibility under the Affordable Care Act,
      nonelderly near-poor adults-those with family incomes of 100-138 percent of the
      federal poverty level-are generally eligible for Medicaid, with no premiums and
      minimal cost sharing. In states that did not expand eligibility, these adults may
      qualify for premium tax credits to purchase Marketplace plans that have out-of
      pocket premiums and cost-sharing requirements. We used data for 2010-15 to
      estimate the effects of Medicaid expansion on coverage and out-of-pocket
      expenses, compared to the effects of Marketplace coverage. For adults with family
      incomes of 100-138 percent of poverty, living in a Medicaid expansion state was
      associated with a 4.5-percentage-point reduction in the probability of being
      uninsured, a $344 decline in average total out-of-pocket spending, a 4.1
      percentage-point decline in high out-of-pocket spending burden (that is, spending
      more than 10 percent of income), and a 7.7-percentage-point decline in the
      probability of having any out-of-pocket spending relative to living in a
      nonexpansion state. These findings suggest that policies that substitute
      Marketplace for Medicaid eligibility could lower coverage rates and increase out
      of-pocket expenses for enrollees.

PMID- 29364737
TI  - Speaking up about Lighting up in Public: Examining Psychosocial Correlates of
      Smoking and Vaping Assertive Communication Intentions among U.S. Adults.
AB  - Against a backdrop of increasing smoke-free policies, electronic cigarette use,
      and discussion about public health risks posed by smoking and vaping, this study
      examines psychosocial predictors of intentions to ask others not to use e
      cigarettes (vape) and smoke - i.e., assertive communication intentions. A
      national sample of U.S. adults (n = 474) reported assertive communication
      intentions for public venues. Psychosocial correlates included perceived risks of
      exposure to secondhand smoke (SHSe) and secondhand vapor (SHVe), SHSe and SHVe
      attitudes, subjective norms, and perceived self-efficacy. Separate linear
      regression models were conducted for smoking and vaping assertive communication
      intention outcomes. Perceived risks and self-efficacy were associated with
      greater vaping and smoking assertive communication intentions; subjective norms
      were only significant for vaping assertive communication intentions. Although a
      majority of respondents indicated they were unlikely to intervene to voice
      objections about SHSe and SHVe in public venues, this study suggests that
      incidental or intentional messages and policies that influence perceptions of
      risk, norms, and efficacy could affect willingness to voice objections about
      others' vaping and smoking in public.

PMID- 29364738
TI  - Mutation Analysis of Families with Autosomal Dominant Congenital Cataract: A
      Recurrent Mutation in the CRYBA1/A3 Gene Causing Congenital Nuclear Cataract.
AB  - PURPOSE: To identify the CRYBA1/A3 mutation spectrum and analyze the genotype
      phenotype correlations in Chinese families with congenital cataract. METHODS:
      Family history and clinical data of 47 unrelated families with autosomal dominant
      congenital cataract (ADCC) were recorded. CRYBA1/A3 gene sequencing was applied
      to identify the causative mutation. Haplotypes were constructed using closely
      linked microsatellite markers and intragenic single-nucleotide polymorphisms
      (SNPs) to compare the affected haplotype in three families. RESULTS: Nuclear
      cataract was the most common type of ADCC in Chinese families, accounting for
      42.6% (20/47). A recurrent CRYBA1/A3 deletion mutation (DeltaG91) was identified
      in three families (6.4%) with nonprogressive nuclear congenital cataract.
      Different haplotypes segregated with the mutation in each family. CONCLUSIONS: A
      recurrent DeltaG91CRYBA1/A3 mutation occurs independently in 6.4% of the Chinese
      families with autosomal dominant nuclear cataracts and most likely represents a
      mutational hot spot, which underscores the relations between nonprogressive
      nuclear cataract and CRYBA1/A3.

PMID- 29364739
TI  - An examination of current stroke rehabilitation practice in Peru: Implications
      for interprofessional education.
AB  - This study aimed to better understand current clinical practice of rehabilitation
      professionals in Lima, Peru, and to explore the existence of and potential for
      interprofessional collaboration. A secondary purpose was to assess rehabilitation
      professionals' agreement with evidence-based stroke rehabilitation statements and
      confidence performing stroke rehabilitation tasks prior to and following an
      interprofessional stroke rehabilitation training. Current clinical practice for
      rehabilitation professionals in Peru differs from high-income counties like the
      United States, as physical therapists work with dysphagia and feeding,
      prosthetist orthotists serve a strictly technical role, and nurses have a limited
      role in rehabilitation. Additionally, while opportunity for future
      interprofessional collaboration within stroke rehabilitation exists, it appears
      to be discouraged by current health system policies. Pre- and post-training
      surveys were conducted with a convenience sample of 107 rehabilitation
      professionals in Peru. Survey response options included endorsement of
      professionals for rehabilitation tasks and a Likert scale of agreement and
      confidence. Training participants largely agreed with evidence-based stroke
      rehabilitation statements. Differences in opinion remained regarding the
      prevalence of dysphagia and optimal frequency of therapy post-stroke.
      Substantially increased agreement post-training was seen in favour of early
      initiation of stroke rehabilitation and ankle foot orthosis use. Participants
      were generally confident performing traditional profession-specific interventions
      and educating patients and families. Substantial increases were seen in
      respondents' confidence to safely and independently conduct bed to chair
      transfers and determine physiological stability. Identification of key
      differences in rehabilitation professionals' clinical practice in Peru is a first
      step toward strengthening the development of sustainable rehabilitation systems
      and interprofessional collaboration.

PMID- 29364740
TI  - The Paradoxical Outcomes of Observing Others' Exercise Behavior on Social Network
      Sites: Friends' Exercise Posts, Exercise Attitudes, and Weight Concern.
AB  - This study examined the implications of observing others' exercise behavior on
      social network sites (SNSs). Social cognitive theory and social comparison theory
      were used to make predictions about the conditions under which individuals' (N =
      232) exposure to exercise-related SNS posts from others in their social network
      were related to their weight concerns and exercise attitudes. The results
      revealed a paradox in which observing others' exercise posts was associated with
      both adaptive and maladaptive responses. The number of exercise-related SNS posts
      received from members of respondents' social networks was associated with greater
      weight concern, and this relationship was stronger among respondents who viewed
      exercise-related posts from network members who were similar to respondents. Yet,
      among respondents who had a tendency to make appearance-related upward social
      comparisons, the number of others' exercise-related SNS posts received was
      associated with pro-exercise attitudes.

PMID- 29364741
TI  - Obesity is a significant susceptibility factor for idiopathic AA amyloidosis.
AB  - BACKGROUND: To investigate obesity as susceptibility factor in patients with
      idiopathic AA amyloidosis. METHODS: Clinical, biochemical and genetic data were
      obtained from 146 patients with AA amyloidosis. Control groups comprised 40
      patients with long-standing inflammatory diseases without AA amyloidosis and 56
      controls without any inflammatory disease. FINDINGS: Patients with AA amyloidosis
      had either familial Mediterranean fever (FMF) or long-standing rheumatic diseases
      as underlying inflammatory disease (n = 111, median age 46 years). However, in a
      significant proportion of patients with AA amyloidosis no primary disease was
      identified (idiopathic AA; n = 37, median age 60 years). Patients with idiopathic
      AA amyloidosis were more obese and older than patients with AA amyloidosis
      secondary to FMF or rheumatic diseases. Serum leptin levels correlated with the
      body mass index (BMI) in all types of AA amyloidosis. Elevated leptin levels of
      more than 30 ug/l were detected in 18% of FMF/rheumatic + AA amyloidosis and in
      40% of patients with idiopathic AA amyloidosis (p = .018). Finally, the SAA1
      polymorphism was confirmed as a susceptibility factor for AA amyloidosis
      irrespective of the type of the disease. CONCLUSIONS: Obesity, age and the SAA1
      polymorphism are susceptibility factors for idiopathic AA amyloidosis. Recent
      advances in treatment of FMF and rheumatic disorders will decrease the incidence
      of AA amyloidosis due to these diseases. Idiopathic AA, however, might be an
      emerging problem in the ageing and increasingly obese population.

PMID- 29364742
TI  - Distress Tolerance Interacts With Negative Life Events to Predict Depressive
      Symptoms Across Adolescence.
AB  - Adolescence is a vulnerable period for the development of depressive disorders.
      Recent research has demonstrated the importance of distress tolerance in the
      onset and maintenance of depression during adulthood; however, little is known
      about its role in predicting depressive symptoms among adolescents. The current
      study examines the effect of distress tolerance and co-occurring negative life
      events on the developmental trajectory of depressive symptoms from middle to late
      adolescence. Our sample included 117 adolescent boys and girls (44.4% female,
      54.6% White). Participants were, on average, 16 years old at baseline (SD = 0.90)
      and completed self-report inventories of negative life events and depressive
      symptoms; distress tolerance was assessed using a behavioral measure. Utilizing a
      latent growth curve approach, we found a significant interaction between distress
      tolerance and negative life events in predicting increases in depressive symptoms
      over time. Follow-up analyses suggest that negative life events were associated
      with greater increases in depressive symptoms over time for adolescents with
      lower levels of distress tolerance only. The study highlights the moderating role
      of distress intolerance in the relation between negative life events and
      depressive symptoms, and underscores the importance of targeting distress
      tolerance for treating depression among youth.

PMID- 29364743
TI  - Comparison Of The I-Gel Supraglottic And King Laryngotracheal Airways In A
      Simulated Tactical Environment.
AB  - BACKGROUND: When working in a tactical environment there are several different
      airway management options that exist. One published manuscript suggests that when
      compared to endotracheal intubation, the King LT laryngotracheal airway (KA)
      device minimizes time to successful tube placement and minimizes exposure in a
      tactical environment. However, comparison of two different blind insertion
      supraglottic airway devices in a tactical environment has not been performed.
      This study compared the I-Gel airway (IGA) to the KA in a simulated tactical
      environment, to determine if one device is superior in minimizing exposure and
      minimizing time to successful tube placement. METHODS: This prospective
      randomized cross over trial was performed using the same methods and tactical
      environment employed in a previously published study, which compared endotracheal
      intubation versus the KA in a tactical environment. The tactical environment was
      simulated with a one-foot vertical barrier. The participants were paramedic
      students who wore an Advanced Combat Helmet (ACH) and a ballistic vest (IIIA)
      during the study. Participants were then randomized to perform tactical airway
      management on an airway manikin with either the KA or the IGA, and then again
      using the alternate device. The participants performed a low military type crawl
      and remained in this low position during each tube placement. We evaluated the
      time to successful tube placement between the IGA and KA. During attempts,
      participants were videotaped to monitor their height exposure above the barrier.
      Following completion, participants were asked which airway device they preferred.
      Data was analyzed using Student's t-test across the groups for time to
      ventilation and height of exposure. RESULTS: In total 19 paramedic students who
      were already at the basic EMT level participated. Time to successful placement
      for the KA was 39.7 seconds (95%CI: 32.7-46.7) versus 14.4 seconds (95%CI: 12.0
      16.9) for the IGA, p < 0.001. Maximum height exposure of the helmet above a one
      foot vertical barrier for the KA resulted in 1.42 inches of exposure (95%CI: 0.38
      0.63) compared to the IGA with 1.42 inches, 95%CI:0.32-0.74, p = 0.99. On
      questioning 100% of the participants preferred the IGA device over the KA.
      CONCLUSION: In a simulated tactical environment placement of the IGA for airway
      management was faster than with the KA, but there was no difference in regard to
      exposure. Additionally, all the participants preferred using the IGA device over
      the KA.

PMID- 29364744
TI  - What did first-year students experience during their interprofessional education?
      A qualitative analysis of e-portfolios.
AB  - Interprofessional collaboration is an essential approach to comprehensive patient
      care. As previous studies have argued, interprofessional education (IPE) must be
      integrated in a stepwise, systematic manner in undergraduate health profession
      education programmes. Given this perspective, first-year IPE is a critical
      opportunity for building the foundation of interprofessional collaborative
      practice. This study aims to explore the first-year students' learning processes
      and the longitudinal changes in their perceptions of learning in a year-long IPE
      programme. Data were collected at a Japanese medical university, in which
      different pedagogical approaches are adopted in the IPE programme. Some of these
      approaches include interprofessional problem-based learning, early exposure, and
      interactive lecture-based teaching. The students are required to submit written
      reflections as a formative assessment. This study conducted an inductive thematic
      analysis of 104 written reflections from a series of e-portfolios of 26 first
      year students. The themes related to learning outcomes from student perspectives
      included communication (e.g., active listening and intelligible explanation),
      teams and teamwork (e.g., mutual engagement and leadership),
      roles/responsibilities as a group member (e.g., self-directed learning and
      information literacy), and roles/responsibilities as a health professional (e.g.,
      understanding of the student's own professional and mutual respect in an
      interprofessional team). The study also indicated three perspectives of students'
      learning process at different stages of the IPE, i.e., processes by which
      students became active and responsible learners, emphasised the enhancement of
      teamwork, and developed their own interprofessional identities. This study
      revealed the first-year students' learning processes in the year-long IPE
      programme and clarified the role of the first-year IPE programme within the
      overall curriculum. The findings suggest that the students' active participation
      in the IPE programme facilitated their fundamental understanding of
      communication/teamwork and identity formation as a health professional in
      interprofessional collaborative practice.

PMID- 29364745
TI  - Do Gold Humanism Honor Society Inductees Differ From Their Peers in Empathy,
      Patient-Centeredness, Tolerance of Ambiguity, Coping Style, and Perception of the
      Learning Environment?
AB  - : Construct: Induction into the Gold Humanism Honor Society (GHHS) during medical
      school is recognized as an indicator of humanistic orientation and behavior.
      Various attitudes and interpersonal orientations including empathy and patient
      centeredness have been posited to translate into behaviors constituting
      humanistic care. BACKGROUND: To our knowledge there has never been a
      longitudinal, multi-institutional empirical study of the attitudinal and
      interpersonal orientations correlated with GHHS membership status. APPROACH: We
      used the American Medical Association Learning Environment Study (LES) data set
      to explore attitudinal correlates associated with students whose behaviors are
      recognized by their peers as being exceptionally humanistic. Specifically, we
      examined whether empathy, patient-centeredness, tolerance of ambiguity, coping
      style, and perceptions of the learning environment are associated with GHHS
      membership status. We further considered to what extent GHHS members arrive in
      medical school with these attitudinal correlates and to what extent they change
      and evolve differentially among GHHS members compared to their non-GHHS peers.
      Between 2011 and 2015, 585 students from 13 North American medical schools with
      GHHS chapters participated in the LES, a longitudinal cohort study using a
      battery of validated psychometric measures including the Jefferson Scale of
      Empathy, Patient-Practitioner Orientation Scale and Tolerance of Ambiguity
      Questionnaire. In the final survey administration, students self-identified as
      GHHS inductees or not (non-GHHS). T tests, effect sizes, and longitudinal
      generalized mixed-effects models examined the differences between GHHS and non
      GHHS students. RESULTS: Students inducted into GHHS scored significantly higher
      on average over 4 years than non-GHHS inductees on clinical empathy, patient
      centered beliefs, and tolerance of ambiguity. GHHS students reported higher
      levels of empathy and patient-centeredness at medical school matriculation. This
      difference persists in the 4th year of medical school and when controlling for
      time, race, gender, and school. CONCLUSIONS: GHHS inductees enter medical school
      with different attitudes and beliefs than their non-GHHS classmates. Although
      humanistic attitudes and beliefs vary over time during students' 4 years, the gap
      between the two groups remains constant. Medical schools may want to consider
      selecting for specific humanistic traits during admissions as well as fostering
      the development of humanism through curricular interventions.

PMID- 29364746
TI  - Descriptive Analysis Of Mental Health-Related Presentations To Emergency Medical
      Services.
AB  - OBJECTIVE: In many developed countries, a lack of community-based mental health
      services is driving increased utilization of emergency medical services (EMS). In
      this descriptive study, we sought to describe the demographic and clinical
      characteristics of mental health-related EMS presentations in Victoria,
      Australia. METHODS: A retrospective observational study of EMS presentations
      occurring between January and December 2015. Computer Aided Dispatch and
      electronic patient care record data were extracted from an electronic data
      warehouse. Characteristics of EMS-attended mental health presentations were
      described and compared to other EMS-attended patients using descriptive
      statistics. RESULTS: Of the total 504,676 EMS attendances, 48,041 (9.5%) were
      mental health presentations. In addition, 4,708 (6.6%) cases managed by a
      paramedic or nurse via the EMS secondary telephone triage service also involved
      mental health complaints. EMS-attended mental health patients were younger and
      more often female compared to other patients attended by EMS. Most mental health
      patients were transported to hospital (74.4%); however, paramedics provided
      treatment to significantly fewer mental health patients compared to other EMS
      attended patients (12.4% vs. 50.3%, p < 0.001%). The majority of mental health
      patients (76.8%) had a documented mental health history. Social or emotional
      issues were the most common presentation in mental health patients aged <=15
      years (19.1%); whereas, for patients aged >=65 years, anxiety was the most common
      clinical presentation (41.2%). For patients undergoing secondary triage, 52.5%
      were frequent callers or anxiety presentations. A total of 27.7% of triaged
      patients were referred to an alternative service, while 24.6% were managed under
      an existing care plan. CONCLUSION: Mental health-related cases represent one in
      ten EMS attendances in Victoria. A large proportion of mental health
      presentations receive little intervention by EMS, and could benefit from
      community-based services provided by mental health clinicians.

PMID- 29364748
TI  - Roles, processes, and outcomes of interprofessional shared decision-making in a
      neonatal intensive care unit: A qualitative study.
AB  - Shared decision-making provides an opportunity for the knowledge and skills of
      care providers to synergistically influence patient care. Little is known about
      interprofessional shared decision-making processes in critical care settings. The
      aim of this study was to explore interprofessional team members' perspectives
      about the nature of interprofessional shared decision-making in a neonatal
      intensive care unit (NICU) and to determine if there are any differences in
      perspectives across professional groups. An exploratory qualitative approach was
      used consisting of semi-structured interviews with 22 members of an
      interprofessional team working in a tertiary care NICU in Canada. Participants
      identified four key roles involved in interprofessional shared decision-making:
      leader, clinical experts, parents, and synthesizer. Participants perceived that
      interprofessional shared decision-making happens through collaboration, sharing,
      and weighing the options, the evidence and the credibility of opinions put
      forward. The process of interprofessional shared decision-making leads to a well
      informed decision and participants feeling valued. Findings from this study
      identified key concepts of interprofessional shared decision-making, increased
      awareness of differing professional perspectives about this process of shared
      decision-making, and clarified understanding of the different roles involved in
      the decision-making process in an NICU.

PMID- 29364749
TI  - Effect of mobilization with movement on lateral knee pain due to proximal
      tibiofibular joint hypomobility.
AB  - This case report describes a 45-year-old female who presented with lateral knee
      pain over the right proximal tibiofibular joint (PTFJ) managed unsuccessfully
      with rest, medications, bracing, injection, and physiotherapy. Clinical diagnosis
      of PTFJ hypomobility was based on concordant symptom reproduction with palpatory
      tenderness, accessory motion testing, and restricted anterior glide of the
      fibula. Intervention consisted of Mulligan's mobilization with movement and
      taping over the right PTFJ with immediate improvements noticed in pain, range of
      motion, and function. The patient was seen twice a week and was discharged after
      four treatment sessions. A follow-up after 6 months revealed that the patient was
      pain free and fully functional.

PMID- 29364750
TI  - PTSD Latent Classes and Class Transitions Predicted by Distress and Fear
      Disorders in Disaster-Exposed Adolescents.
AB  - This study aimed to determine the population-based typologies of posttraumatic
      stress disorder (PTSD) symptomatology, the longitudinal patterns of transitions
      across these typologies, and the predictive effects of distress and fear disorder
      symptoms on these transitions in a frequently referred but scantly studied
      population of traumatized youth. A sample of 1,278 Chinese adolescents (54.0%
      girls) with a mean age of 13.4 years (SD = 0.8, range = 12-16) completed 2-wave
      surveys 2.5 and 3.5 years after a major disaster. Psychopathological symptoms
      were assessed with the UCLA PTSD Reaction Index for DSM-IV, the Depression Self
      Rating Scale for Children, and the Screen for Child Anxiety Related Emotional
      Disorders. Latent class analyses identified 4 classes characterized by high,
      reexperiencing/hypervigilance, dysphoria, and low symptoms, respectively at each
      time point. Latent transition analyses revealed relatively high levels of
      temporal stability within low symptom and dysphoria classes but relatively high
      probabilities of migration from re-experiencing/hypervigilance and high symptom
      classes into lower symptom classes. Multinomial logistic regression analyses
      found that some of the between-class movements during the year were predicted by
      baseline distress or fear disorders. This study provides an initial depiction of
      both quantitative and qualitative changes in youth's long-term PTSD symptom
      patterns over time and gives a further elucidation of other forms of posttrauma
      psychopathology's impacts on PTSD course. These findings carry implications for
      ongoing evaluation and adjustable intervention individually tailored to youth's
      PTSD manifestations and comorbidities in the long-term disaster aftermath.

PMID- 29364747
TI  - Rare and Common Variants Conferring Risk of Tooth Agenesis.
AB  - We present association results from a large genome-wide association study of
      tooth agenesis (TA) as well as selective TA, including 1,944 subjects with
      congenitally missing teeth, excluding third molars, and 338,554 controls, all of
      European ancestry. We also tested the association of previously identified risk
      variants, for timing of tooth eruption and orofacial clefts, with TA. We report
      associations between TA and 9 novel risk variants. Five of these variants
      associate with selective TA, including a variant conferring risk of orofacial
      clefts. These results contribute to a deeper understanding of the genetic
      architecture of tooth development and disease. The few variants previously
      associated with TA were uncovered through candidate gene studies guided by mouse
      knockouts. Knowing the etiology and clinical features of TA is important for
      planning oral rehabilitation that often involves an interdisciplinary approach.

PMID- 29364751
TI  - High glucose induces inflammatory responses in HepG2 cells via the oxidative
      stress-mediated activation of NF-kappaB, and MAPK pathways in HepG2 cells.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of high glucose
      (HG) on inflammation in HepG2 cells. METHODS: The molecular mechanisms linking HG
      to inflammation was assessed in HepG2 cells exposed to HG (33 mM). RESULTS: The
      results showed that HG significantly enhanced TNF-alpha, IL-6 and PAI-1
      expression in HepG2 cells. Increased expression of cytokines was accompanied by
      enhanced phosphorylation of JNK, P38, ERK and IKKalpha/IKKbeta. In addition, JNK,
      ERK, P38 and NF-kB inhibitors could significantly attenuate HG-induced expression
      of TNF-alpha, IL-6 and PAI-1. Furthermore, HG could promote the generation of
      reactive oxygen species (ROS), while N-acetyl cysteine, a ROS scavenger, had an
      inhibitory effect on the expression of TNF-alpha, IL-6 and PAI-1 in HG-treated
      cells. CONCLUSIONS: Our results indicated that HG-induced inflammation is
      mediated through the generation of ROS and activation of the MAPKs and NF-kB
      signalling pathways in HepG2 cells.

PMID- 29364752
TI  - Positive Outcomes of Optimizing Student-Preceptor Continuity in a Traditional
      Block Clerkship.
AB  - PROBLEM: Student-preceptor discontinuity during 3rd-year clerkships limits the
      quality and quantity of supervision, teaching, and feedback. Although
      longitudinal integrative clerkships increase continuity and are associated with
      improved student and preceptor experience, they require schoolwide curricular
      reform. Alternative innovations enhancing student-preceptor relationships within
      the constraints of a traditional block clerkship may demonstrate similar
      benefits. INTERVENTION: We piloted a continuity-enhanced general pediatric
      ambulatory schedule during 2 consecutive clerkship blocks in 2013. Students in
      the continuity-enhanced model (n = 29) were assigned 1-3 primary clinic
      preceptors, whereas those in the traditional model (n = 30) worked with 5-8. Data
      were gathered from student assessments and anonymous student and preceptor
      surveys. We used t and Fisher's exact tests to compare the two groups and
      performed thematic analysis of free-text survey comments. CONTEXT: Our school
      utilizes a block clerkship model with approximately 30 students rotating through
      the pediatric clerkship every 8 weeks. During the 3-week ambulatory portion,
      students spend 8 half days in the general pediatric ambulatory clinic. At the
      conclusion of each clinic, attendings completed brief student evaluation cards.
      Traditionally, student and attending schedules were created independently,
      resulting in transient supervisory relationships and dissatisfaction with
      clinical engagement, feedback, and evaluation. OUTCOME: Seventy-three percent
      (43/59) of the students completed the survey. Ten general ambulatory attendings
      collectively completed 87.5% (35/40) of the monthly surveys. Continuity students
      received significantly more narrative evaluation comments (10.6 vs. 5.8, p <.
      001) from general ambulatory clinic attendings and were more likely to have at
      least one general ambulatory clinic attending endorse being able to provide
      meaningful feedback and evaluation (n = 29, 100% vs. n = 20, 66.7%, p <. 001).
      Continuity students were also more likely to endorse being able to ask at least
      one of these attendings for a letter of recommendation (71.4% vs. 9.1%, p <. 001)
      and to have at least one general ambulatory clinic attending endorse being able
      to provide a meaningful letter of recommendation if asked (62.1% vs. 3.3%, p <.
      001). Students (88.4%) and attendings (85.7%) preferred the continuity-enhanced
      schedule. The most frequent theme of both student and attending free-text survey
      remarks were relationships and assessment. LESSONS LEARNED: Intentional
      scheduling of clerkship students to enhance preceptor continuity resulted in
      significant positive outcomes echoing the relationship-based educational benefits
      of longitudinal clerkships, particularly in regards to student assessment and
      feedback. Clerkship directors and other medical educators should consider
      implementing small changes within block clerkships to maximize student-preceptor
      continuity.

PMID- 29364753
TI  - The effects of some antibiotics from cephalosporin groups on the
      acetylcholinesterase and butyrylcholinesterase enzymes activities in different
      tissues of rats.
AB  - In our study, it was aimed to investigate the effects of cefazolin, cefuroxime,
      and cefoperazon injected to rats on acetylcholinesterase (AChE) and
      butyrylcholinesterase (BChE) enzyme activities in the heart, brain, eye, liver,
      and kidney tissues of rats. Liver AChE activity at the 1st and 3rd hours of
      cefuroxime groups was higher than the control group at the same time (p <.05).
      The AChE activity of the heart tissue decreased in the cefazolin group compared
      to the control group at the same hour, whereas it increased in the cefuroxime
      group (p <.05). AChE activities of kidney tissue of cefazolin and cefuroxime
      groups were lower than those of the same control group on the 3rd and started to
      increase on the next hours (p <.05). BChE activity is measured in tissues
      increased within the first three hours and decreased significantly within the
      first hour in the cefoperazone group (p <.05).

PMID- 29364754
TI  - Effects of the craniocervical flexion and isometric neck exercise compared in
      patients with chronic neck pain: A randomized controlled trial.
AB  - INTRODUCTION: The present study compared the effects of neck isometric exercise
      (NIE) and craniocervical flexion exercise (CFE) on cervical lordosis, muscle
      endurance of cervical flexion, neck disability index (NDI), and active cervical
      range of motion (ACROM) in all three planes in patients with non-specific,
      chronic neck pain (CNP). MATERIALS AND METHODS: Forty-one patients from a
      university hospital-based rehabilitation center were randomly assigned to an
      experimental (22 patients performing CFE) or control (19 patients performing NIE)
      group. All patients performed three 30-second repetitions of stretching exercises
      for the neck flexor, extensor, lateral flexor, and rotator as warm-up and cool
      down exercises. The patients in the experimental group then underwent CFE 30
      minutes/day, 3 times a week, for 8 weeks, while the control group underwent NIE.
      The main outcome measures were pain on visual analogue scale (VAS) and perceived
      disability based on the neck disability index (NDI). The secondary outcomes were
      cervical lordosis measured by an absolute rotation angle (ARA), muscle endurance
      of cervical flexion, and ACROM. RESULTS: Both groups showed improved pain, NDI,
      endurance of the cervical flexor muscles, and ACROM in all three planes after 8
      weeks (p < 0.001 for all). All these outcomes, except for the NDI, showed
      significantly greater improvements following CFE than following NIE (p < 0.05 for
      all). In particular, a significantly improved ARA of cervical lordosis was found
      following CFE but not following NIE (p < 0.05). CONCLUSIONS: CFE targeted at
      retraining the craniocervical flexor muscles was useful for improving or
      restoring the pain, cervical lordosis, and neck-related function disorders among
      patients with non-specific CNP.

PMID- 29364755
TI  - Differences in Caregiving Outcomes and Experiences by Sexual Orientation and
      Gender Identity.
AB  - PURPOSE: The purpose of this study was to determine whether caregiving
      experiences and their health-related outcomes differ by sexual orientation and
      gender identity in a representative U.S. caregiver sample. METHODS: A secondary
      data analysis was performed of the cross-sectional, nationally representative
      National Alliance for Caregiving online survey that was conducted in 2014. To
      account for the study design, we used sampling weights and then added propensity
      score weighting to account for imbalances between LGBT respondents and their
      heterosexual and cisgender counterparts, that is, non-LGBT caregivers. Outcomes
      consisted of caregivers' self-reported health, financial strain, physical strain,
      and emotional stress. RESULTS: LGBT caregivers were significantly younger, more
      racially and ethnically diverse, less likely to be married, and more likely to be
      of low socioeconomic status than their non-LGBT counterparts. Caregiving
      experiences and intensity were similar, but after controlling for demographic and
      caregiving characteristics, LGBT caregivers were significantly more likely to
      report financial strain and showed trends toward elevated levels of poor health
      and emotional stress. Physical strain was similar by LGBT status. CONCLUSION:
      Caregiving itself is universal, yet LGBT caregivers differed demographically and
      were more likely to report financial strain compared with non-LGBT caregivers.

PMID- 29364756
TI  - Erectile Dysfunction Symptoms in Polydrug Dependents Seeking Treatment:
      Methodological Issues.

PMID- 29364758
TI  - Introduction to Volume 1 of JOPT Special Issue.

PMID- 29364757
TI  - A Force on the Crown and Tug of War in the Periodontal Complex.
AB  - The load-bearing dentoalveolar fibrous joint is composed of biomechanically
      active periodontal ligament (PDL), bone, cementum, and the synergistic entheses
      of PDL-bone and PDL-cementum. Physiologic and pathologic loads on the
      dentoalveolar fibrous joint prompt natural shifts in strain gradients within
      mineralized and fibrous tissues and trigger a cascade of biochemical events
      within the widened and narrowed sites of the periodontal complex. This review
      highlights data from in situ biomechanical simulations that provide tooth
      movements relative to the alveolar socket. The methods and subsequent results
      provide a reasonable approximation of strain-regulated biochemical events
      resulting in mesial mineral formation and distal resorption events within
      microanatomical regions at the ligament-tethered/enthesial ends. These
      biochemical events, including expressions of biglycan, decorin, chondroitin
      sulfated neuroglial 2, osteopontin, and bone sialoprotein and localization of
      various hypertrophic progenitors, are observed at the alkaline phosphatase
      positive widened site, resulting in mineral formation and osteoid/cementoid
      layers. On the narrowed side, tartrate-resistant acid phosphatase regions can
      lead to a sequence of clastic activities resulting in resorption pits in bone and
      cementum. These strain-regulated biochemical and subsequently biomineralization
      events in the load-bearing periodontal complex are critical for maintenance of
      the periodontal space and overall macroscale joint biomechanics.

PMID- 29364759
TI  - Erectile Dysfunction Symptoms in Polydrug Abusers Seeking Treatment.

PMID- 29364760
TI  - Life Goals Increase Self-regulation among Male Patients with Alcohol Use
      Disorder.
AB  - BACKGROUND: Alcohol use disorder (AUD) has been conceptualized as a chronic self
      regulation failure. OBJECTIVES: The aim of this study was to examine the most
      probable pathways related to self-regulation among patients with AUD. In this
      study, a hypothetical model was proposed that focused on the relationship between
      risk factors (extrinsic life goals, emotion dysregulation) and protective factors
      (intrinsic life goals, self-control, and abstinence self-efficacy). METHODS: Male
      patients with AUD (N = 188) were recruited from alcohol centers of four
      psychiatric hospitals between March 2015 and September 2015. All participants
      completed psychological assessments, including the Future Oriented Goals Scale
      (FOGS), the Alcohol Abstinence Self-Efficacy Scale (AASE), the Brief Self-Control
      Scale (BSCS), and the Difficulties in Emotion Regulation Scale (DERS) as well as
      sociodemographic characteristics. RESULTS: The final model was found to be a good
      fit to data. In testing indirect effects, it was shown that intrinsic life goals
      via emotion dysregulation, self-control, and alcohol abstinence self-efficacy
      decreased alcohol self-regulation failure. On the other hand, extrinsic life
      goals via these factors increased alcohol self-regulation failure.
      Conclusions/Importance: These results suggest that intrinsic goals might
      indirectly be the important and protective factors for AUD. Moreover, the
      findings implicate that self-regulation through goal setting may be necessary to
      alleviate symptoms and improve function among patients with AUD.

PMID- 29364761
TI  - Serotonin-2B/2C Receptors Mediate Bovine Ciliary Muscle Contraction: Role in
      Intraocular Pressure Regulation.
AB  - PURPOSE: To study the pharmacological profile of the serotonin (5
      hydroxytryptamine [5-HT]) receptor subtype mediating contractions in bovine
      isolated ciliary muscles. METHODS: Ciliary muscle strips were isolated from
      bovine eyeballs and mounted in organ baths containing aerated (95% O2, 5% CO2)
      Krebs buffer solution maintained at 37 degrees C. Each muscle strip was attached
      at 1 end to a Grass Force-displacement Transducer connected to a Polyview
      Computer System for recording changes in isometric tension. After an
      equilibration period, ciliary muscle strips were exposed to selective agonists
      and antagonists of 5-HT receptors. RESULTS: Both selective and nonselective
      agonists for 5-HT produced concentration-dependent contractions of isolated
      ciliary muscles with the following rank order of potency: BW723C86>alpha-methyl-5
      HT>MK-212>>8-hydroxy-DPAT>quipazine>R-DOI>>5-HT>>tryptamine. The selective 5-HT2
      receptor antagonists, M-100907 (5-HT2A), RS-127445 (5-HT2B), and RS-102221 (5
      HT2C), produced noncompetitive inhibition of the contractile effects of selective
      agonists yielding antagonist potency (pKB) values of 251 +/- 27.2 nM (n = 4),
      52.5 +/- 6.3 nM (n = 4), and 79.4 +/- 9.5 nM (n = 4), respectively. CONCLUSION:
      On the basis of the profile of activity of selective agonists and antagonists, we
      conclude that the 5-HT2B and 5-HT2C receptor subtypes appear to be the
      predominant serotonin receptors that mediate the contractile action of this amine
      in bovine isolated ciliary muscles.

PMID- 29364762
TI  - Injection Drug Use Trajectories among Migrant Populations: A Narrative Review.
AB  - BACKGROUND: Dual epidemics of injection drug use and blood-borne disease,
      characterized as "syndemics," are present in a range of settings. Behaviors that
      drive such syndemics are particularly prevalent among mobile drug-using
      populations, for whom cross-border migration may pose additional risks.
      OBJECTIVES: This narrative review aims to characterize the risk factors for
      injection drug use initiation associated with migration, employing a risk
      environment framework and focusing on the San Diego-Tijuana border region as the
      most dynamic example of these phenomena. METHODS: Based on previous literature,
      we divide migration streams into three classes: intra-urban, internal, and
      international. We synthesized existing literature on migration and drug use to
      characterize how mobility and migration drive the initiation of injection drug
      use, as well as the transmission of hepatitis and HIV, and to delineate how these
      might be addressed through public health intervention. RESULTS: Population mixing
      between migrants and receiving communities and the consequent transmission of
      social norms about injection drug use create risk environments for injection drug
      use initiation. These risk environments have been characterized as a result of
      local policy environments, injection drug use norms in receiving communities,
      migration-related stressors, social dislocation, and infringement on the rights
      of undocumented migrants. CONCLUSION: Policies that exacerbate risk environments
      for migrants may inadvertently contribute to the expansion of epidemics of
      injection-driven blood-borne disease. Successful interventions that address
      emerging syndemics in border regions may therefore need to be tailored to migrant
      populations and distinguish between the vulnerabilities experienced by different
      migration classes and border settings.

PMID- 29364763
TI  - Gender and Cultural Adaptations for Diversity: A Systematic Review of Alcohol and
      Substance Abuse Interventions for Latino Males.
AB  - BACKGROUND: Latino men are disproportionately affected by the consequences of
      alcohol and substance abuse when compared to non-Latino white men. Latino men
      also face greater barriers to accessing, engaging, and completing alcohol and
      substance abuse treatment services. Culturally adapted interventions are promoted
      to overcome these barriers. However, the effectiveness of these efforts is
      unclear. OBJECTIVES: The purpose of this review was to summarize the published
      evidence regarding gender-adapted and culturally adapted alcohol and substance
      abuse treatment that aims to improve physical, behavioral, and social outcomes in
      Latino men. METHODS: A systematic literature search was conducted for articles
      reporting on culturally and/or gender-adapted alcohol and/or substance abuse
      interventions designed exclusively for Latino adults, including a Latino
      population sample of at least 10% and any proportion of Latino male participants.
      A thematic analysis based on predetermined themes was used to evaluate the nature
      of adaptations. RESULTS: Searches yielded 2685 titles, resulting in 12 articles
      that fit review parameters. The most scientifically rigorous findings suggest
      culturally adapted interventions may outperform standard treatment. Nevertheless,
      a fraction of the interventions did not improve outcomes compared to standard
      treatment. Considering the scarce number of publications, it is difficult to
      discern if null findings reflect ineffective interventions or methodological
      limitations. CONCLUSIONS: While studies are limited and findings are mixed,
      culturally tailored work shows promise. The growth rate of the Latino population
      and the current epidemic nature of substance abuse in the United States generate
      urgency to identify methods to diminish the disparate burden of alcohol and
      substance abuse in Latinos.

PMID- 29364764
TI  - Adverse Childhood Experiences and Early Initiation of Marijuana and Alcohol Use:
      The Potential Moderating Effects of Internal Assets.
AB  - INTRODUCTION: Early adolescence is a critical risk period for initiation of
      substance use. Internal assets (IAs), which are individual qualities guiding
      positive choices, and adverse childhood experiences (ACEs) are important
      protective and risk factors, respectively, against substance use. The purpose of
      this study is to investigate whether IAs modify associations between ACEs and
      early initiation of alcohol and marijuana use. METHOD: Data were from 9th and
      11th graders who completed the 2013 Minnesota Student Survey (n = 79,339).
      Students reported on experiences of abuse, household dysfunction, and substance
      use. Multivariable logistic regressions examined associations between different
      types of ACEs and substance use. Interactions between IAs and ACEs were added to
      models to test effect modification. For significant interactions, main effects
      models were re-estimated at different percentiles of IAs. RESULT: IAs moderated
      associations of both abuse and household dysfunction with early initiation of
      marijuana (p <.003) and alcohol (p =.007) for females but not for males. For
      females with low IAs, odds of early initiation of marijuana were approximately
      twice as high as students without any ACEs. A similar pattern was detected for
      females' initiation of alcohol use. No effect modification was detected for IAs
      and experiencing only abuse or household dysfunction on initiation. CONCLUSION:
      Special attention should be paid to improving IAs among girls who have already
      experienced ACEs. Future research should examine protective factors that buffer
      the effects of ACEs for boys.

PMID- 29364765
TI  - Young Adult Female Cancer Survivors' Concerns About Future Children's Health and
      Genetic Risk.
AB  - As young adult female cancer survivors (aged 18-35) make family-building
      decisions, understanding the specific nature of their concerns is important. We
      evaluated survivors' concerns about potential health risks to future children
      including genetic susceptibility for cancer with an internet-based survey study
      (N = 187). Sixty-five percent reported concern about passing on a genetic cancer
      risk to their children, and scores did not vary regardless of association with
      cancer at high risk for genetic transmission. Genetic counseling and education
      about family-building options may be important to survivors concerned about
      health risks to offspring to support family-building decisions based on
      personalized medical information.

PMID- 29364766
TI  - Does Documented Brief Intervention Predict Decreases in Alcohol Use in Primary
      Care?
AB  - BACKGROUND: Brief intervention (BI) is recommended for patients with unhealthy
      alcohol use, but the effectiveness of BI in usual care settings remains unclear.
      OBJECTIVE: We evaluated whether BI predicts decreases in drinking 6 months after
      a positive screen for unhealthy alcohol use. METHOD: We enrolled patients who
      recently screened positive for unhealthy alcohol use during a routine screen in
      Veterans Health Administration primary care. We conducted medical record review
      to assess whether providers documented advice to reduce or abstain, feedback
      about risks to health, feedback about how patient drinking compares to norms or
      recommended limits, and discussion of drinking-related goals. BI elements were
      coded from 7 days before the date of the positive screen to 60 days after. We
      conducted baseline and 6-month follow-up telephone interviews to assess change in
      past 30-day drinking. We fit regression models examining each BI element and
      another model for the total count of instances of any combination of elements.
      RESULTS: Of the 327 patients included, 86% had at least one documented instance
      of receiving advice, 86% had risk feedback, 55% had normative feedback, 38% had
      goal discussion, and 75% had three or more instances of any combination of
      elements of BI. None of the individual BI elements, nor the total number of
      instances, were significantly associated with decreased drinking. CONCLUSIONS:
      Results suggest that provider documentation of elements of BI and increasing
      numbers of instances of BI elements were not associated with decreased heavy
      drinking at 6-month follow-up among patients identified with unhealthy alcohol
      use.

PMID- 29364769
TI  - Introduction to Volume 2 of JOPT Special Issue.

PMID- 29364768
TI  - The Effectiveness of Internet- and Field-Based Methods to Recruit Young Adults
      Who Use Prescription Opioids Nonmedically.
AB  - BACKGROUND: Nonmedical prescription opioid (NMPO) use is a problem among young
      adults, yet young NMPO users are a diverse population that has been challenging
      to engage in overdose prevention and harm reduction programs. OBJECTIVES: This
      study compared the effectiveness and characteristics of persons recruited through
      two different sampling strategies to inform research and intervention efforts
      with young adult NMPO users. METHODS: We analyzed data from the Rhode Island
      Young Adult Prescription Drug Study (RAPiDS), which enrolled persons aged 18 to
      29 who reported past 30-day NMPO use. We compared the characteristics of two
      samples recruited simultaneously between February 2015 and February 2016. One
      sample was recruited using field-based strategies (e.g., respondent-driven
      sampling, transit ads), and a second from internet sources (e.g., online
      classifieds). RESULTS: Among 198 eligible participants, the median age was 25
      (IQR: 22, 27), 130 (65.7%) were male, 123 (63.1%) were white, and 150 (78.1%)
      resided in urban areas. A total of 79 (39.9%) were recruited using field-based
      strategies and 119 (60.1%) were recruited from internet sources. Internet
      recruited persons were younger (median = 24 [IQR: 21, 27] vs. 26 [IQR: 23, 28]
      years) and more likely to reside in rural areas (16.2% vs. 5.3%), although this
      finding was marginally significant. Field-recruited participants were more likely
      to have been homeless (36.7% vs. 17.7%), have been incarcerated (39.7% vs.
      21.8%), and engage in daily NMPO use (34.6% vs. 14.5%). CONCLUSIONS: Multipronged
      outreach methods are needed to engage the full spectrum of young adult NMPO users
      in prevention and harm reduction efforts.

PMID- 29364771
TI  - Female Chess Players Outperform Expectations When Playing Men.
AB  - Stereotype threat has been offered as a potential explanation of differential
      performance between men and women in some cognitive domains. Questions remain
      about the reliability and generality of the phenomenon. Previous studies have
      found that stereotype threat is activated in female chess players when they are
      matched against male players. I used data from over 5.5 million games of
      international tournament chess and found no evidence of a stereotype-threat
      effect. In fact, female players outperform expectations when playing men. Further
      analysis showed no influence of degree of challenge, player age, nor prevalence
      of female role models in national chess leagues on differences in performance
      when women play men versus when they play women. Though this analysis contradicts
      one specific mechanism of influence of gender stereotypes, the persistent
      differences between male and female players suggest that systematic factors do
      exist and remain to be uncovered.

PMID- 29364773
TI  - European University Students' Experiences and Attitudes toward Campus Alcohol
      Policy: A Qualitative Study.
AB  - BACKGROUND: Many studies indicate that a substantial part of the student
      population drinks excessively, yet most European universities do not have an
      alcohol policy. In the absence of an alcohol guideline at universities and the
      easy access to alcohol sold at the student cafeteria, for instance, this has the
      potential to place students at risk of overconsumption, which has adverse health
      consequences. OBJECTIVES: Therefore, our study objectives were to explore and
      compare university students' experiences and attitudes toward alcohol policy on
      their campus using a qualitative approach. METHODS: 29 focus group discussions
      (FGDs) were conducted among students from universities in five European
      countries: Belgium (4 FGDs), Denmark (6 FGDs), France (5 FGDs), Hungary (6 FGDs),
      and the Slovak Republic (8 FGDs), with a total number of 189 participants.
      RESULTS: Across the five European countries, students recognized that alcohol was
      a big problem on their campuses yet they knew very little, if any, about the
      rules concerning alcohol on their campus. CONCLUSIONS: Students will not support
      an on campus alcohol restriction and a policy should therefore focus on
      prevention initiatives.

PMID- 29364772
TI  - Improving Breast Cancer Surgical Treatment Decision Making: The iCanDecide
      Randomized Clinical Trial.
AB  - Purpose This study was conducted to determine the effect of iCanDecide, an
      interactive and tailored breast cancer treatment decision tool, on the rate of
      high-quality patient decisions-both informed and values concordant-regarding
      locoregional breast cancer treatment and on patient appraisal of decision making.
      Methods We conducted a randomized clinical trial of newly diagnosed patients with
      early-stage breast cancer making locoregional treatment decisions. From 22
      surgical practices, 537 patients were recruited and randomly assigned online to
      the iCanDecide interactive and tailored Web site (intervention) or the iCanDecide
      static Web site (control). Participants completed a baseline survey and were
      mailed a follow-up survey 4 to 5 weeks after enrollment to assess the primary
      outcome of a high-quality decision, which consisted of two components, high
      knowledge and values-concordant treatment, and secondary outcomes (decision
      preparation, deliberation, and subjective decision quality). Results Patients in
      the intervention arm had higher odds of making a high-quality decision than did
      those in the control arm (odds ratio, 2.00; 95% CI, 1.37 to 2.92; P = .0004),
      which was driven primarily by differences in the rates of high knowledge between
      groups. The majority of patients in both arms made values-concordant treatment
      decisions (78.6% in the intervention arm and 81.4% in the control arm). More
      patients in the intervention arm had high decision preparation (estimate, 0.18;
      95% CI, 0.02 to 0.34; P = .027), but there were no significant differences in the
      other decision appraisal outcomes. The effect of the intervention was similar for
      women who were leaning strongly toward a treatment option at enrollment compared
      with those who were not. Conclusion The tailored and interactive iCanDecide Web
      site, which focused on knowledge building and values clarification, positively
      affected high-quality decisions largely by improving knowledge compared with
      static online information. To be effective, future patient-facing decision tools
      should be integrated into the clinical workflow to improve decision making.

PMID- 29364774
TI  - Resistance Is Futile: Engineering the Adoptive T-Cell Therapies of the Future.

PMID- 29364767
TI  - Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging.
AB  - BACKGROUND: Thrombectomy is currently recommended for eligible patients with
      stroke who are treated within 6 hours after the onset of symptoms. METHODS: We
      conducted a multicenter, randomized, open-label trial, with blinded outcome
      assessment, of thrombectomy in patients 6 to 16 hours after they were last known
      to be well and who had remaining ischemic brain tissue that was not yet
      infarcted. Patients with proximal middle-cerebral-artery or internal-carotid
      artery occlusion, an initial infarct size of less than 70 ml, and a ratio of the
      volume of ischemic tissue on perfusion imaging to infarct volume of 1.8 or more
      were randomly assigned to endovascular therapy (thrombectomy) plus standard
      medical therapy (endovascular-therapy group) or standard medical therapy alone
      (medical-therapy group). The primary outcome was the ordinal score on the
      modified Rankin scale (range, 0 to 6, with higher scores indicating greater
      disability) at day 90. RESULTS: The trial was conducted at 38 U.S. centers and
      terminated early for efficacy after 182 patients had undergone randomization (92
      to the endovascular-therapy group and 90 to the medical-therapy group).
      Endovascular therapy plus medical therapy, as compared with medical therapy
      alone, was associated with a favorable shift in the distribution of functional
      outcomes on the modified Rankin scale at 90 days (odds ratio, 2.77; P<0.001) and
      a higher percentage of patients who were functionally independent, defined as a
      score on the modified Rankin scale of 0 to 2 (45% vs. 17%, P<0.001). The 90-day
      mortality rate was 14% in the endovascular-therapy group and 26% in the medical
      therapy group (P=0.05), and there was no significant between-group difference in
      the frequency of symptomatic intracranial hemorrhage (7% and 4%, respectively;
      P=0.75) or of serious adverse events (43% and 53%, respectively; P=0.18).
      CONCLUSIONS: Endovascular thrombectomy for ischemic stroke 6 to 16 hours after a
      patient was last known to be well plus standard medical therapy resulted in
      better functional outcomes than standard medical therapy alone among patients
      with proximal middle-cerebral-artery or internal-carotid-artery occlusion and a
      region of tissue that was ischemic but not yet infarcted. (Funded by the National
      Institute of Neurological Disorders and Stroke; DEFUSE 3 ClinicalTrials.gov
      number, NCT02586415 .).

PMID- 29364775
TI  - Evidence for the Upward Spiral Stands Steady: A Response to Nickerson (2018).

PMID- 29364776
TI  - Modeling emissions for three-dimensional atmospheric chemistry transport models.
AB  - : Poor air quality is still a threat for human health in many parts of the world.
      In order to assess measures for emission reductions and improved air quality,
      three-dimensional atmospheric chemistry transport modeling systems are used in
      numerous research institutions and public authorities. These models need accurate
      emission data in appropriate spatial and temporal resolution as input. This paper
      reviews the most widely used emission inventories on global and regional scales
      and looks into the methods used to make the inventory data model ready.
      Shortcomings of using standard temporal profiles for each emission sector are
      discussed, and new methods to improve the spatiotemporal distribution of the
      emissions are presented. These methods are often neither top-down nor bottom-up
      approaches but can be seen as hybrid methods that use detailed information about
      the emission process to derive spatially varying temporal emission profiles.
      These profiles are subsequently used to distribute bulk emissions such as
      national totals on appropriate grids. The wide area of natural emissions is also
      summarized, and the calculation methods are described. Almost all types of
      natural emissions depend on meteorological information, which is why they are
      highly variable in time and space and frequently calculated within the chemistry
      transport models themselves. The paper closes with an outlook for new ways to
      improve model ready emission data, for example, by using external databases about
      road traffic flow or satellite data to determine actual land use or leaf area. In
      a world where emission patterns change rapidly, it seems appropriate to use new
      types of statistical and observational data to create detailed emission data sets
      and keep emission inventories up-to-date. IMPLICATIONS: Emission data are
      probably the most important input for chemistry transport model (CTM) systems.
      They need to be provided in high spatial and temporal resolution and on a grid
      that is in agreement with the CTM grid. Simple methods to distribute the
      emissions in time and space need to be replaced by sophisticated emission models
      in order to improve the CTM results. New methods, e.g., for ammonia emissions,
      provide grid cell-dependent temporal profiles. In the future, large data fields
      from traffic observations or satellite observations could be used for more
      detailed emission data.

PMID- 29364777
TI  - A Manifesto for the Age-Friendly Movement: Developing a New Urban Agenda.
AB  - Developing age-friendly cities and communities has become a key part of policies
      aimed at improving the quality of life of older people in urban areas. The World
      Health Organization has been especially important in driving the "age-friendly"
      agenda, notably through its global network of age-friendly cities and
      communities. Despite the expansion and achievements of the network, challenges
      remain in responding to the growth of inequality and the impact of economic
      austerity on aging policies. Against the background of these limitations, this
      article sets out a "manifesto for the age-friendly movement" aimed at raising the
      aspirations of what is now a worldwide movement. The areas covered in the
      manifesto are challenging social inequality, widening participation, coproducing
      and codesigning age-friendly communities, encouraging multisectorial and
      multidisciplinary collaboration, and integrating research with policy. The
      article concludes with a discussion on developing age-friendly work as a
      contribution to a new agenda for urban aging.

PMID- 29364778
TI  - Suicide attempters in Abu Dhabi: Is criminal prosecution associated with
      patients' guardedness?
AB  - The objective of this study was to examine the relationship between legal status
      and guardedness in patients who attempted suicide in Abu Dhabi, United Arab
      Emirates. The consultation-liaison team assessed 355 patients admitted for
      suicidal/self-injurious behavior, recording their guardedness before knowing
      whether they were legally charged. Patients who were legally charged for the
      suicidal act (n = 139) were 1.6 times (p = .03) more guarded in volunteering
      information than patients who were not legally charged. Legally charging suicide
      attempters might have a negative impact on risk assessment and psychiatric care.

PMID- 29364779
TI  - "I am tired of having to prove that my husband was dead." Dealing with practical
      matters in bereavement and the impact on the bereaved.
AB  - This paper reports on experiences of dealing with practical matters after death.
      Semi structured interviews with bereaved individuals were thematically analyzed.
      Within the theme of coping, dealing with practical matters was a significant
      stressor and was found to be extremely challenging, time consuming, and to
      negatively impact on mental and emotional well-being. This study adds new
      insights on the challenges experienced by the bereaved when attending to
      practical matters and may help to inform the design of bereavement support,
      inform standard operating procedures of businesses, and government bereavement
      leave legislation.

PMID- 29364780
TI  - Positive Attitude Toward Math Supports Early Academic Success: Behavioral
      Evidence and Neurocognitive Mechanisms.
AB  - Positive attitude is thought to impact academic achievement and learning in
      children, but little is known about its underlying neurocognitive mechanisms.
      Using a large behavioral sample of 240 children, we found that positive attitude
      toward math uniquely predicted math achievement, even after we accounted for
      multiple other cognitive-affective factors. We then investigated the neural
      mechanisms underlying the link between positive attitude and academic achievement
      in two independent cohorts of children (discovery cohort: n = 47; replication
      cohort: n = 28) and tested competing hypotheses regarding the differential roles
      of affective-motivational and learning-memory systems. In both cohorts, we found
      that positive attitude was associated with increased engagement of the
      hippocampal learning-memory system. Structural equation modeling further revealed
      that, in both cohorts, increased hippocampal activity and more frequent use of
      efficient memory-based strategies mediated the relation between positive attitude
      and higher math achievement. Our study is the first to elucidate the
      neurocognitive mechanisms by which positive attitude influences learning and
      academic achievement.

PMID- 29364781
TI  - Pathogen- and Danger-Associated Molecular Patterns and the Cytokine Response in
      Sepsis.
AB  - The sepsis syndrome is a systemic host inflammatory response accompanied by organ
      dysfunction in response to invading microbial pathogens. The host recognizes both
      danger and pathogens through its pattern recognition receptors on immune cells.
      These receptors bind to pathogen- (PAMP) and danger- (DAMP) associated molecular
      patterns derived from microbes and host tissues, respectively. These processes
      set in motion a cascade of events in host cells and tissue, which activate
      multiple cytokines that serve as activators of the host inflammatory response as
      well as eventually lead to resolution of the response if the host recovers. The
      following article describes some of these DAMPs and PAMPs, and how they activate
      pathways that activate the host cytokine immune response to injury and infection.

PMID- 29364782
TI  - Implementing an interdisciplinary intergenerational program using the Cyber
      Seniors(r) reverse mentoring model within higher education.
AB  - Intergenerational service-learning in higher education positively affects older
      adults and students, but little is known about the effectiveness of
      interdisciplinary, reverse mentoring programs that use technology as the medium
      of bringing generations together. This study describes an intergenerational
      service-learning program that utilizes reverse mentoring within higher education,
      the "Engaging Generations Program," at a midsized public university in New
      England where students help older adults learn about technology, and students
      gain communication and teaching skills. In this article, we outline how the
      program was implemented, present quantitative data on participation outcomes for
      students and older adults and qualitative data from older adults, and discuss
      best practices. Analysis of pre/post surveys found that students' attitudes
      toward aging improved (p < 0.01) and older adults interest in technology improved
      (p < 0.05) after program participation. Best practices identified included:
      multiple meetings with the same pair to deepen friendships, in-person training
      for student leaders, student responsibility for scheduling, tailoring sessions to
      each participant, student documentation of meetings, and active involvement by
      community partners.

PMID- 29364784
TI  - Assessing the relationships among stress, god-mediated control, and psychological
      distress/well-being: Does the level of education matter?
AB  - One of the primary functions of religion is to help people cope with stressful
      life events. The purpose of the current study is to see if God-mediated control
      beliefs perform this stress-buffering function. God-mediated control refers to
      the belief that people work together with God to reduce the effects of unwanted
      stressors in their lives. An effort is made to probe this relationship more
      deeply by seeing whether the stress moderating function of God-mediated control
      beliefs varies across levels of educational attainment. Findings from a recent
      nationwide survey suggest that strong God-mediated control beliefs reduce the
      magnitude of the relationship between stress and depressive symptoms, anxiety,
      happiness, and hope, but only among more highly educated study participants. In
      contrast, God-mediated control beliefs do not appear to influence the
      relationship between stress and distress/well-being among study participants with
      lower levels of educational attainment.

PMID- 29364783
TI  - "Don't bother about me." The grief and mental health of bereaved adolescents.
AB  - Death of a relative or friend is a potentially disruptive event in the lives of
      adolescents. To provide targeted help, it is crucial to understand their grief
      and mental health experiences. Thematic analysis of 39 semistructured telephone
      interviews yielded two themes: Grieving apart together and Personal growth. High
      self-reliance and selective sharing were common. Feelings of guilt and "why"
      questions seemed more pronounced among the suicide bereaved. There was strong
      evidence of personal growth, increased maturity, and capacity to deal with
      personal mental health/suicidality. Despite its devastating effects, experiencing
      a death can be a catalyst for positive mental health.

PMID- 29364786
TI  - Corrigendum.

PMID- 29364785
TI  - Just between us: Exclusive communications in online social networks.
AB  - Social media websites such as Facebook are used for relationship development and
      maintenance often through self-disclosure and sharing of personal information.
      However, not all forms of social media communication may be equally suitable for
      this task. This paper explores users' norms about the appropriateness of using
      private vs. public Facebook messages to communicate different kinds of personal
      information, and the effectiveness of these types of communication in building
      relationships. Study 1, a survey, revealed that users endorse conflicting
      expectations about preferences for receiving information publicly or privately.
      Study 2, a field experiment testing the effects of private versus public Facebook
      communications on actual relationship development using participants' own
      Facebook pages, suggested that private messages lead to greater closeness.

PMID- 29364787
TI  - Examination of the latent factor structure and construct validity of the stigma
      of suicide scale-short form.
AB  - A major limitation of research on attitudes toward suicide is that most measures
      lack evidence of a stable factor structure. To investigate the structure of
      recently developed stigma of suicide scale-short form (SOSS-SF), we conducted an
      exploratory factor analysis in a sample of 499 undergraduates. Results revealed a
      three-factor structure: Stigma, Isolation/Depression, and
      Glorification/Normalization. We also identified good convergent and discriminant
      validity between the SOSS-SF and related constructs. In a separate sample of 570
      undergraduates, a confirmatory factor analysis (CFA) demonstrated adequate fit
      for the three-factor model. In addition, a multiple-group CFA demonstrated
      invariance across gender.

PMID- 29364788
TI  - Sharing is caring: The potential of the sharing economy to support aging in
      place.
AB  - This article explores innovative applications of sharing economy services that
      have the potential to support a population aging in place, especially the "oldest
      old," aged 85 and older, and their caregivers. A mixed-methods study conducted by
      the MIT AgeLab examined perceptions of and experiences with sharing economy
      services, ultimately finding opportunities and barriers to use. Thus, although
      sharing economy services have potential to support aging in place, to do so
      successfully will require reconstructing how older adults, family caregivers,
      aging service professionals, gerontology educators, and gerontology students
      conceptualize and deliver care to an aging population. We suggest examples for
      gerontology educators to integrate into their classrooms to further cultivate an
      appreciation among students of multiple approaches to intervention, including
      those that leverage sharing economy and technology-enabled platforms to support
      older adults and their caregivers.

PMID- 29364789
TI  - Pregaming among Latina/o emerging adults: Do acculturation and gender matter?
AB  - Among ethnic minority groups, Latina/o emerging adults are most likely to engage
      in pregaming, a risky drinking practice. This study examined how U.S.
      acculturation and enculturation are associated with pregaming and the extent to
      which gender moderates this relation in a sample of 312 Latina/o emerging adults
      (18 - 25 years of age). Results indicated that men consumed more alcohol when
      pregaming than women, but there were no gender differences in pregaming
      frequency. Results also showed that lower levels of U.S. acculturation were
      associated with greater alcohol consumption while pregaming for men, but not
      women. Gender did not moderate the association between acculturation and
      pregaming frequency. This study highlights the need to account for gender when
      examining sociocultural determinants of high risk drinking behaviors such as
      pregaming among Latina/o emerging adults.

PMID- 29364790
TI  - Commentaries on Viewpoint: Principles, insights, and potential pitfalls of the
      noninvasive determination of muscle oxidative capacity by near-infrared
      spectroscopy.

PMID- 29364791
TI  - Last Word on Viewpoint: Principles, insights, and potential pitfalls of the
      noninvasive determination of muscle oxidative capacity by near-infrared
      spectroscopy.

PMID- 29364793
TI  - Threats to the Internal Validity of Experimental and Quasi-Experimental Research
      in Healthcare.
AB  - The article defines, describes, and discusses the seven threats to the internal
      validity of experiments discussed by Donald T. Campbell in his classic 1957
      article: history, maturation, testing, instrument decay, statistical regression,
      selection, and mortality. These concepts are said to be threats to the internal
      validity of experiments because they pose alternate explanations for the apparent
      causal relationship between the independent variable and dependent variable of an
      experiment if they are not adequately controlled. A series of simple diagrams
      illustrate three pre-experimental designs and three true experimental designs
      discussed by Campbell in 1957 and several quasi-experimental designs described in
      his book written with Julian C. Stanley in 1966. The current article explains why
      each design controls for or fails to control for these seven threats to internal
      validity.

PMID- 29364792
TI  - What we learned through asking about evidence: A model for interdisciplinary
      student engagement.
AB  - Traditional university learning modalities of lectures and examinations do not
      prepare students fully for the evolving and complex world of gerontology and
      geriatrics. Students involved in more active, self-directed learning can develop
      a wider breadth of knowledge and perform better on practical examinations. This
      article describes the Evidence in Aging (EIA) study as a model of active learning
      with the aim of preparing students to be effective interdisciplinary researchers,
      educators, and leaders in aging. We focus particularly on the experiences and
      reflections of graduate students who collaborated with faculty mentors on study
      design, data collection, and analysis. Students acquired new methodological
      skills, gained exposure to diverse disciplines, built interdisciplinary
      understanding, and cultivated professional development. The EIA study is a model
      for innovative student engagement and collaboration, interactive learning, and
      critical scholarly development. Lessons learned can be applied to a range of
      collaborative research projects in gerontology and geriatrics education.

PMID- 29364794
TI  - Kidney Allocation: New Contributions to an Ongoing Challenge.

PMID- 29364795
TI  - [Analysis of the Cochrane Review: Early Discharge Hospital at Home. Cochrane
      Database Syst Rev. 2017;6:CD000356.]
AB  - Hospital at home is a service that provides active treatment by healthcare
      professionals in the patient's home for a condition that otherwise would require
      acute hospital in-patient care. However, the clinical bene t of this intervention
      and its effect on health costs are not established. This Cochrane systematic
      review aimed to assess the effectiveness and costs of managing patients with
      hospital at home compared with inpatient hospital care. A systematic review of
      the literature was carried out by searching the following databases to 9 January
      2017: Cochrane Effective Practice and Organization of Care Group (EPOC) register,
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase,
      CINAHL, EconLit and clinical trials registries. Thirty-two randomized trials (2
      of which unpublished), including 4746 patients, were included. The present review
      provides insuf cient objective evidence of economic bene t (through a reduction
      in hospital length of stay) or improved health outcomes.

PMID- 29364796
TI  - Injuries in Portuguese Amateur Youth Football Players: A Six Month Prospective
      Descriptive Study.
AB  - INTRODUCTION: This study analyzed the incidence and characteristics of injuries
      sustained by amateur youth football players in Portugal during season 2015 -
      2016. MATERIAL AND METHODS: This is an observational descriptive study. We
      analyzed Portuguese youth football players' injuries over six months of a season.
      A total of 529 players were divided according to their age in two groups (Under
      17 and Under-19). Data on injuries were collected. RESULTS: Throughout all 62
      062.0 hours of exposure recorded, 248 injuries were reported in 173 different
      players. The average incidence of injury was 3.87 (95% CI = 2.81; 4.94) per 1000
      hours of football exposure. There was a significantly higher average incidence of
      injury during matches - 14.22 (95% CI = 10.35; 18.09) per 1000 hours of exposure 
      when compared to the average incidence of injury during training - 2.06 (95% CI
      = 1.22; 2.90) per 1000 hours of exposure. This significance was also observed
      when the comparison was made within each age group. A traumatic mechanism was
      involved in 76.6% of all the injuries, while overuse was reported in 12.9%. The
      most common type was the injury that affected muscles and tendons (52.8%). The
      body location most commonly affected by injuries was the thigh (24.6%).
      DISCUSSION: Even though is essential a better characterization of Portuguese
      athletes of younger age groups such as those discussed in this study, the results
      of the studied population are in agreement with the existing literature. However,
      this study provides more information that may be important to better target the
      Portuguese athletes' training for injury prevention. CONCLUSION: This study
      provides descriptive data on injuries developed in a subpopulation of Portuguese
      amateur youth football players that could represent a focus for future
      prevention.

PMID- 29364797
TI  - Anaesthesia in Dental Medicine with Local Infiltrative Anaesthetic Technique
      Versus Diploe Anaesthesia Delivery Systems: Efficacy and Behaviour, an
      Experimental Study.
AB  - INTRODUCTION: This study aimed to compare the analgesic efficacy and the
      influence of local infiltrative anesthesia techniques, with diploe anesthesia, on
      the cardiac rhythmMaterial and Methods: We selected 32 healthy volunteers who
      were given both anaesthetic techniques on tooth 1.4 (0.45 mL of lidocaine with
      adrenaline, 1:80 000). In the first phase, the volunteers underwent periapical
      infiltrative anaesthesia. In the second phase, diploe anaesthesia was performed
      with a QuickSleeper(r) device. The parameters analysed were pulp response to the
      electrical test and heart rate of the participants. These parameters were
      evaluated on five different occasions: before anaesthesia (t0), immediately after
      anaesthesia (t1), 15 minutes later (t15), 30 minutes later (t30) and 60 minutes
      later (t60). Statistical analysis of the data was performed using SPSS 2.0
      software, with alpha = 0.05. RESULTS: With the diploe anaesthesia, a level of
      analgesia was obtained faster. There was a slight increase in heart rate soon
      after administration of diploe anaesthesia, which stabilized after t15 of the
      procedure. This technique still proved to be painless. CONCLUSION: Diploe
      anaesthesia demonstrated better results in terms of analgesia than the
      infiltrative anaesthesia. It has been reported to be easy, safe and an effective
      procedure that allows anaesthesia in almost all clinical situations. This
      approach may offer particular advantages for endodontic therapy, providing
      greater comfort for the patient.

PMID- 29364798
TI  - [Selection of Donor-Recipient Pairs in Renal Transplantation: Comparative
      Simulation Results].
AB  - INTRODUCTION: Implemented in 2007 by Ordinance No. 6357, allocation rules of
      cadaveric donor kidneys seek to distribute equitably a scarce community resource
      to patients who can improve their survival and quality of life. As stated in the
      aforementioned ordinance these rules must be updated whenever the state of the
      art recommends it. The objective of this work is to evaluate and compare three
      cadaveric donor allocation models: scoring criteria of ordinance no 6537/2007
      (model 1); similar to the previous model but with a lower score for the dialysis
      time (model 2); and a model adapted from the previously proposed color allocation
      system (model 3). MATERIAL AND METHODS: For the purpose of this analysis we
      generated data about 70 cadaveric donors taking into account information
      published regarding blood group distribution and human leucocyte antigens allelic
      and haplotype frequencies of Portuguese voluntary donors. We generated also data
      for a simulated waiting list of 500 first-time kidney transplant candidates.
      RESULTS: We observed fewer candidates selected by model 3 with more than 3 human
      leucocyte antigens mismatches (39.3%) when compared to those selected by model 1
      with more than 3 human leucocyte antigens mismatches (57.1%, p < 0.01).
      DISCUSSION: In our analysis, model 3 selects transplant candidates with a lower
      number of human leucocyte antigens mismatches when compared to the adapted rules
      for kidney allocation of Ordinance No. 6537/2007 (model 1) without penalizing
      candidates with a longer time on dialysis. CONCLUSION: The analysis and
      discussion of the best rules for allocation of such a scarce resource as organs
      from deceased donors should be a continuous and adaptive process inherent to
      transplant candidate's waiting list evolution and mutation.

PMID- 29364799
TI  - Limited Health Literacy in Portugal Assessed with the Newest Vital Sign.
AB  - INTRODUCTION: In Portugal, health literacy has started to be addressed through
      national policies, but research on the topic is still scarce. We aimed to
      estimate the prevalence and sociodemographic correlates of limited health
      literacy in Portugal using an existing health literacy instrument, the Newest
      Vital Sign. MATERIALS AND METHODS: Following cross-cultural adaptation of the
      instrument, a sample of 249 participants was evaluated to assess reliability and
      construct validity of the Newest Vital Sign; the latter was tested assuming
      physicians would score highest, followed by health researchers, then by
      engineering researchers and finally by laypersons from the general population. We
      applied this validated version in a representative sample of 1544 Portuguese
      speaking residents in Portugal aged between 16 and 79 years and quantified the
      associations between limited health literacy and sociodemographic
      characteristics. RESULTS: The instrument showed high reliability (Cronbach's
      alpha = 0.85). Health-related occupation showed association with higher scores in
      the Newest Vital Sign (p trend < 0.001). The prevalence of limited health
      literacy in the Portuguese population was 72.9% (95% CI: 69.4 - 76.4). We found
      no differences between men and women, but persons with limited health literacy
      were significantly older (p < 0.001) and less educated (p < 0.001). DISCUSSION:
      The burden of limited health literacy in Portugal is higher than that in other
      European countries. It should drive a universal precautions approach to health
      communication at all levels of the health system. CONCLUSION: We validated a
      brief and simple instrument and estimated the prevalence of limited health
      literacy in the literate Portuguese population at roughly three out of four
      people.

PMID- 29364800
TI  - [Effects of Speech Therapy in Hospitalized Patients with Post-Stroke Dysphagia: A
      Systematic Review of Observational Studies].
AB  - INTRODUCTION: Since dysphagia may be one of the brain post-stroke consequences,
      the objective of this study was to analyze the average recovery time of patients
      with cerebrovascular accident and dysphagia subjected to speech therapy in a
      hospital bed. MATERIAL AND METHODS: Systematic review performed following the
      'Preferred Reporting Items is Systematic Reviews and MetaAnalyses' instructions.
      The search was performed in different electronic databases, without restriction
      of time and language. The studies were evaluated regarding their methodological
      quality. RESULTS: Of 5671 titles, five studies were included. 176 patients with
      stroke and dysphagia were obtained (aged between 22 and 91 years old - average:
      68.95), with no preference regarding gender. Improvement occurred in 84.26% of
      the subjects and the recovery time was between one and ninety days (average: 22
      days). Randomization, blinding, loss to follow-up and withdrawal were not
      performed with control group in any study. DISCUSSION: The success of
      rehabilitation of oropharyngeal dysphagia as a post-stroke sequela will depend on
      the extent, location of the neurological lesion and early intervention in the
      hospital bed. Despite the recognition of health professionals about the
      importance of swallowing rehabilitation for these patients, there is a lack of
      studies that support an evidence-based practice, although the results point to
      improvements in this regard. CONCLUSION: Speech therapy in hospital bed in post
      stroke hospitalized patients with dysphagia seems to bring satisfactory results
      in the short-term, revealing the importance of diagnosis and early intervention
      in these cases.

PMID- 29364801
TI  - [Retroperitoneal Cellular Angiofibroma: A Rare Gynecological Entity].
AB  - Cellular angiofibroma is a mesenchymal tumor, described in 1997, without gender
      preference, that usually appears at age 40. The vulvovaginal area is the most
      common site in women, mimicking vulvar benign tumors, like Bartholin gland cyst.
      However, there are a few described cases of a deep or extra-pelvic angiofibroma.
      Excision is the treatment of choice and the recurrence rate appears to be low. We
      present the case of a woman with a heterogeneous tumor in the right adnexial
      region. At the surgery, a retroperitoneal tumor was excised and the
      histopathological tissue analysis revealed a cellular angiofibroma.

PMID- 29364802
TI  - [Infectious Mononucleosis and Cholestatic Hepatitis: A Rare Association].
AB  - Infectious mononucleosis is one of the major clinical manifestations of Epstein
      Barr virus infection. In this syndrome, elevation of liver transaminase levels is
      common but cholestasis is rare, with few cases described in the literature. We
      present the case of a 14-year-old female adolescent, admitted to the Emergency
      Room with fever, odynophagia and cervical adenomegaly. She was treated with
      amoxicillin and two days later he presented with jaundice. The analytical
      evaluation was compatible with cholestatic hepatitis and abdominal ultrasound
      revealed hepatosplenomegaly without dilatation of the bile ducts. The diagnosis
      of Epstein-Barr virus infection was confirmed by the presence of serological
      markers. This case aims to raise awareness of a rare manifestation of a common
      infectious agent and, consequently, to the inclusion of acute Epstein-Barr virus
      infection in the differential diagnosis of pediatric cholestatic hepatitis.

PMID- 29364803
TI  - Lead Poisoning: Myoclonus Following Welding Exposure.

PMID- 29364804
TI  - [Post-Traumatic Diaphragmatic Hernia: Limitations of Non-Invasive Ventilation].

PMID- 29364805
TI  - Letter to the Editor: Colonic Perforation.

PMID- 29364806
TI  - Letter to the Editor regarding the article "Prevalence of Hepatitis A Virus
      Antibody in Portuguese Travelers: A New Paradigm".

PMID- 29364807
TI  - Letter to the Editor: The Clear and Present Danger to Portuguese Travelers to the
      Middle East Region.

PMID- 29364808
TI  - [Pediatric tuberculosis].

PMID- 29364809
TI  - [Acute lymphoblastic leukemia: a genomic perspective].
AB  - In parallel to the human genome sequencing project, several technological
      platforms have been developed that let us gain insight into the genome structure
      of human entities, as well as evaluate their usefulness in the clinical approach
      of the patient. Thus, in acute lymphoblastic leukemia (ALL), the most common
      pediatric malignancy, genomic tools promise to be useful to detect patients at
      high risk of relapse, either at diagnosis or during treatment (minimal residual
      disease), and they also increase the possibility to identify cases at risk of
      adverse reactions to chemotherapy. Therefore, the physician could offer patient
      tailored therapeutic schemes. A clear example of the useful genomic tools is the
      identification of single nucleotide polymorphisms (SNPs) in the thiopurine methyl
      transferase (TPMT) gene, where the presence of two null alleles (homozygous or
      compound heterozygous) indicates the need to reduce the dose of mercaptopurine by
      up to 90% to avoid toxic effects which could lead to the death of the patient. In
      this review, we provide an overview of the genomic perspective of ALL, describing
      some strategies that contribute to the identification of biomarkers with
      potential clinical application.

PMID- 29364810
TI  - [A case-series analysis of tuberculosis in pediatric patients treated in a
      tertiary level hospital].
AB  - BACKGROUND: Tuberculosis (TB) remains a challenge because severe forms occur most
      frequently in children under 5 years of age and the diagnosis is complex. The
      objective of this paper was to describe the clinical presentation, frequency,
      diagnostic methods used and response to treatment in children with TB treated at
      a tertiary level hospital. METHODS: The study was retrospective and descriptive
      of a cohort of consecutive cases treated from January 2010 to December 2013.
      Ninety-three medical records of children diagnosed with TB according to the
      definition of the NOM-006-SSA2-2013 were reviewed. Descriptive statistics were
      used for the analysis. RESULTS: From 93 children, 58% were male (mean age of 7
      years), 97% with a history of BCG vaccination, and 6% had contact with a TB case.
      The most frequent clinical forms were pulmonary (30.1%), lymph node (24.7%),
      miliary/disseminated (16.1%), meningeal (13%), and osteal TB (7.5%). The most
      common symptoms were fever and weight loss (50% and 40%, respectively). BAAR and
      culture were positive in 26% and 7% of all cases, respectively. The
      histopathological study was conclusive in 90% of the cases. The treatment was
      successful in 94.6%, with not associated mortality. CONCLUSIONS: The association
      of clinical symptoms with alterations in chest radiography and positive PPD are
      useful in establishing the presumptive diagnosis and an early and appropriate
      treatment.

PMID- 29364811
TI  - [Tuberculosis: the tip of the iceberg].

PMID- 29364812
TI  - [Urinary tract infection caused by Enterobacteriaceae and its relationship with
      vesicoureteral reflux].
AB  - BACKGROUND: The first urinary tract infection can be a marker of a urinary tract
      anomaly, mainly vesicoureteral reflux. The aim of this work was to determine the
      association between isolated enterobacteria with the presence and grade of
      vesicoureteral reflux in neonatal patients with their first urinary tract
      infection. METHODS: A retrospective, observational and analytic study of
      newborns, who were admitted to the Neonatal Department, University Pediatric
      Hospital "Juan Manuel Marquez," in Havana, Cuba, from 1992 to 2013 was conducted.
      The causal microorganism of urinary tract infection was from the
      Enterobacteriaceae family. They were evaluated by radio imaging. The association
      between the presence and grade of vesicoureteral reflux with the causal
      microorganism of the urinary tract infection was analyzed. RESULTS: Newborn
      infants with urinary tract infection (450) were studied. Bacterial isolations in
      the urine cultures corresponded to E. coli in 316 cases (70.2%). The prevalence
      of vesicoureteral reflux was 18.2%. The presence of bacteria corresponding to the
      Enterobacteriaceae family (other than E. coli) had significant risk association
      with vesicoureteral reflux (OR: 2.02; p < 0.01) and vesicoureteral reflux
      classification (for higher grades, p < 0.01). CONCLUSIONS: E. coli is the most
      frequent causal microorganism in neonatal urinary tract infection. However, an
      association between the isolation of a microorganism of the Enterobacteriaceae
      family different to E. coli with the presence of vesicoureteral reflux and mainly
      with higher grades of vesicoureteral reflux exists.

PMID- 29364813
TI  - Systematic review of the current status of programs and general knowledge of
      diagnosis and management of retinoblastoma.
AB  - BACKGROUND: This systematic review aims to report the current knowledge of
      retinoblastoma (Rb) and its implications in Mexico. We analyzed clinical and
      demographic data of patients with Rb at select hospitals with Rb programs or that
      treat and refer patients with Rb, and identified the gaps in practice. We propose
      solutions to improve diagnosis, provide adequate treatment, and improve patient
      uptake. METHODS: A general review was conducted on PubMed of peer-reviewed
      literature on Rb in Mexico. Ophthalmology Department Heads or Directors of Rb
      programs at seven hospitals in Mexico were contacted for data available on their
      patients with Rb. RESULTS: Five hospitals provided clinical data on 777 patients
      with Rb in a period spanning 2000-2015. Of the 122 patients with treatment, 83.4%
      underwent enucleation. From 33 to 45.3% of Rb tumors in Mexico reach an advanced
      intraocular stage of development. Knowledge of the disease is limited, despite
      the fact that the Mexican Retinoblastoma Group has elaborated Rb treatment
      guidelines and is developing a national Rb registry. Especially in the Southern
      states, prevalence and outcomes are comparable to African and Asian countries,
      and only few patients are referred to national treatment centers. Only three
      institutions have comprehensive Rb programs. CONCLUSIONS: There is an immediate
      need in Mexico to expand primary care providers' knowledge of Rb and to expand
      and upgrade current Rb programs to meet the needs of the population adequately.
      Diagnosis and care of Rb patients in Mexico can also be improved by the
      establishment of a national Rb registry and a national early detection program,
      and by increased use of the national treatment protocol.

PMID- 29364814
TI  - Ages and Stages Questionnaire: a global screening scale.
AB  - With standardized screening tools, research studies have shown that developmental
      disabilities can be detected reliably and with validity in children as young as 4
      months of age by using the instruments such as the Ages and Stages Questionnaire.
      In this review, we will focus on one tool, the Ages and Stages Questionnaire, to
      illustrate the usefulness of developmental screening across the globe.

PMID- 29364815
TI  - [Percutaneous closure of ductus arteriosus through an arteriovenous loop in a
      patient with scimitar syndrome].
AB  - BACKGROUND: Scimitar syndrome consists in a rare malformation characterized by a
      partial abnormal connection in one or both right pulmonary veins to the inferior
      vena cava, right lung hypoplasia and systemic circulation from the descending
      aorta. Scimitar syndrome is occasionally associated to other congenital
      malformations, such as patent ductus arteriosus (PDA). CASE REPORT: We report a 4
      year-old patient with "adult" variety of scimitar syndrome associated to
      symptomatic PDA, which was successfully occluded using retrograde guidewire
      established femoral arteriovenous loop with an Amplatzer(r) PDA occluder, without
      complications. CONCLUSIONS: Scimitar syndrome is complex and requires a complete
      hemodynamic study for the determination of the appropriate treatment. Pulmonary
      arterial hypertension is a factor associated with poor prognosis.

PMID- 29364817
TI  - [Parameter fitting for cochlear implant].
AB  - Programming a patient with cochlear impant follows a standardized and
      individualized protocol, although there is a percentage of users in which, for
      some reason, it is not possible to establish appropriate levels of stimulation.
      In these patients, the audiologist has to make adjustments in some special
      parameters such as a change in the strategy, stimulation rate, pulse width, among
      others, in order to obtain an auditory performance as expected.

PMID- 29364816
TI  - [Telangiectatic osteosarcoma in an infant].
AB  - BACKGROUND: Osteosarcoma is one of the most common types of cancer in childhood
      and adolescence and it is the most common malignant bone tumor in this group of
      age. Osteosarcoma is frequently found in long bones of the extremities. There are
      very few cases described in children under 5 years of age, and according to this
      review, none in infants. The telangiectatic variant is uncommon, and there are no
      reported cases before preschool age. CASE REPORT: A 10-month-old female infant
      with a lithic tumor of the ninth right rib, which was classified after resection
      as a telangiectatic osteosarcoma, is presented. CONCLUSIONS: Telangiectatic
      osteosarcoma in the pediatric age is very uncommon. To date, the patient has
      presented good response to treatment, although the prognosis and survival of this
      condition is unknown.

PMID- 29364819
TI  - Traditional Ecological Knowledge: A Different Perspective on Environmental
      Health.

PMID- 29364818
TI  - [Origins of institutional Pediatrics: Maternity and Childhood Hospital of Mexico
      City in the nineteenth century].
AB  - In June of 1866, the empress Carlota founded the Maternity House in the
      Department of Secret Births at the Hospice of the Poor. Upon the reinstatement of
      a republican government, Dr. Ramon Pacheco was appointed director of the
      Maternity House. Shortly after, in February of 1868, Dr. Luis Fernandez Gallardo
      established a pavilion for sick children in the Hospital of San Andres. After
      realizing this pavilion didn't have the adequate conditions to operate properly,
      and in the need of a children's hospital in Mexico City, Dr. Pacheco merged both
      institutions in April 2, 1869 -with the help of Ms. Luciana Arrazola- and founded
      the Maternity and Childhood Hospital, the first institution for the care of ill
      children in the independent Mexico. Ever since it was founded, Dr. Eduardo
      Liceaga was in charge of the children's health. Later, with the help of the
      presidents Juarez, Lerdo de Tejada and Diaz, he was able to consolidate the
      hospital in academic and health services aspects. This noble institution closed
      its doors on February 5, 1905, upon its incorporation to the General Hospital of
      Mexico, after 36 years of working for the welfare of Mexican children.

PMID- 29364821
TI  - Effects of protein-coated nanofibers on conformation of gingival fibroblast
      spheroids: potential utility for connective tissue regeneration.
AB  - Deep wounds in the gingiva caused by trauma or surgery require a rapid and robust
      healing of connective tissues. We propose utilizing gas-brushed nanofibers coated
      with collagen and fibrin for that purpose. Our hypotheses are that protein-coated
      nanofibers will: (i) attract and mobilize cells in various spatial orientations,
      and (ii) regulate the expression levels of specific extracellular matrix (ECM)
      associated proteins, determining the initial conformational nature of dense and
      soft connective tissues. Gingival fibroblast monolayers and 3D spheroids were
      cultured on ECM substrate and covered with gas-blown poly-(DL-lactide-co
      glycolide) (PLGA) nanofibers (uncoated/coated with collagen and fibrin). Cell
      attraction and rearrangement was followed by F-actin staining and confocal
      microscopy. Thicknesses of the cell layers, developed within the nanofibers, were
      quantified by ImageJ software. The expression of collagen1alpha1 chain
      (Col1alpha1), fibronectin, and metalloproteinase 2 (MMP2) encoding genes was
      determined by quantitative reverse transcription analysis. Collagen- and fibrin-
      coated nanofibers induced cell migration toward fibers and supported cellular
      growth within the scaffolds. Both proteins affected the spatial rearrangement of
      fibroblasts by favoring packed cell clusters or intermittent cell spreading.
      These cell arrangements resembled the structural characteristic of dense and soft
      connective tissues, respectively. Within three days of incubation, fibroblast
      spheroids interacted with the fibers, and grew robustly by increasing their
      thickness compared to monolayers. While the ECM key components, such as
      fibronectin and MMP2 encoding genes, were expressed in both protein groups,
      Col1alpha1 was predominantly expressed in bundled fibroblasts grown on collagen
      fibers. This enhanced expression of collagen1 is typical for dense connective
      tissue. Based on results of this study, our gas-blown, collagen- and fibrin
      coated PLGA nanofibers are viable candidates for engineering soft and dense
      connective tissues with the required structural characteristics and functions
      needed for wound healing applications. Rapid regeneration of these layers should
      enhance healing of open wounds in a harsh oral environment.

PMID- 29364820
TI  - Air Pollution and Performance-Based Physical Functioning in Dutch Older Adults.
AB  - BACKGROUND: Functional limitations are a major cause for needing care and
      institutionalization among older adults. Exposure to air pollution has been
      suggested to be associated with increased functional limitations in older people.
      OBJECTIVE: Our objective was to assess the association between air pollution and
      physical functioning in Dutch older adults. METHODS: We analyzed data on
      performance-based (walking speed, ability to rise from a chair, putting on and
      taking off a cardigan, balance test) and self-reported physical functioning for
      1,762 participants of the Longitudinal Aging Study Amsterdam, who participated in
      measurement cycles performed in 2005/2006, 2008/2009, and 2011/2012. Annual
      average outdoor air pollution concentrations [nitrogen dioxide (NO2), nitrogen
      oxides (NOx), particulate matter with diameters <=2.5MUm (PM2.5), <=10MUm (PM10),
      and 2.5-10MUm (PMcoarse), and PM2.5 absorbance] at the home address at the start
      of the first measurement cycle were estimated using land-use regression models.
      Analyses were performed using mixed models with random participant intercepts
      adjusting for potential confounders. RESULTS: Exposure to most air pollutants was
      associated with reduced performance-based physical functioning; for example, an
      interquartile range increase in NO2 exposure was associated with a 0.22 (95%
      confidence interval: 0.03, 0.42) lower performance test score in fully adjusted
      models, equivalent to the difference in performance score between participants
      who differed by 9 mo in age. Exposure to air pollution was generally not
      statistically significantly associated with self-reported functional limitations,
      and not associated with a faster decline in performance-based physical
      functioning over the study period. CONCLUSION: This study suggests that exposure
      to air pollution may adversely affect physical performance of older adults in the
      Netherlands. https://doi.org/10.1289/EHP2239.

PMID- 29364822
TI  - Anticipating the puck.

PMID- 29364823
TI  - 2017 JCO orthodontic practice study: Part 3 practice growth and staff data.

PMID- 29364824
TI  - Weekly aligner changes to improve Invisalign treatment efficiency.

PMID- 29364825
TI  - Pain and quality of life in patients undergoing guided piezocorticision- assisted
      orthodontic treatment.

PMID- 29364826
TI  - Two-phase treatment of anterior open bite.

PMID- 29364827
TI  - Multidisciplinary management of post-ankylosis malocclusion and mandibular
      deformity.

PMID- 29364828
TI  - Multipurpose ligation technique for elastomeric chain.

PMID- 29364829
TI  - The Integrative Method Based on the Module-Network for Identifying Driver Genes
      in Cancer Subtypes.
AB  - With advances in next-generation sequencing(NGS) technologies, a large number of
      multiple types of high-throughput genomics data are available. A great challenge
      in exploring cancer progression is to identify the driver genes from the variant
      genes by analyzing and integrating multi-types genomics data. Breast cancer is
      known as a heterogeneous disease. The identification of subtype-specific driver
      genes is critical to guide the diagnosis, assessment of prognosis and treatment
      of breast cancer. We developed an integrated frame based on gene expression
      profiles and copy number variation (CNV) data to identify breast cancer subtype
      specific driver genes. In this frame, we employed statistical machine-learning
      method to select gene subsets and utilized an module-network analysis method to
      identify potential candidate driver genes. The final subtype-specific driver
      genes were acquired by paired-wise comparison in subtypes. To validate
      specificity of the driver genes, the gene expression data of these genes were
      applied to classify the patient samples with 10-fold cross validation and the
      enrichment analysis were also conducted on the identified driver genes. The
      experimental results show that the proposed integrative method can identify the
      potential driver genes and the classifier with these genes acquired better
      performance than with genes identified by other methods.

PMID- 29364830
TI  - Genome-Wide Identification and Comparative Analysis of the 3-Hydroxy-3
      methylglutaryl Coenzyme A Reductase (HMGR) Gene Family in Gossypium.
AB  - Terpenes are the largest and most diverse class of secondary metabolites in
      plants and play a very important role in plant adaptation to environment. 3
      Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is a rate-limiting enzyme in
      the process of terpene biosynthesis in the cytosol. Previous study found the HMGR
      genes underwent gene expansion in Gossypium raimondii, but the characteristics
      and evolution of the HMGR gene family in Gossypium genus are unclear. In this
      study, genome-wide identification and comparative study of HMGR gene family were
      carried out in three Gossypium species with genome sequences, i.e., G. raimondii,
      Gossypium arboreum, and Gossypium hirsutum. In total, nine, nine and 18 HMGR
      genes were identified in G. raimondii, G. arboreum, and G. hirsutum,
      respectively. The results indicated that the HMGR genes underwent gene expansion
      and a unique gene cluster containing four HMGR genes was found in all the three
      Gossypium species. The phylogenetic analysis suggested that the expansion of HMGR
      genes had occurred in their common ancestor. There was a pseudogene that had a 10
      bp deletion resulting in a frameshift mutation and could not be translated into
      functional proteins in G. arboreum and the A-subgenome of G. hirsutum. The
      expression profiles of the two pseudogenes showed that they had tissue-specific
      expression. Additionally, the expression pattern of the pseudogene in the A
      subgenome of G. hirsutum was similar to its paralogous gene in the D-subgenome of
      G. hirsutum. Our results provide useful information for understanding cytosolic
      terpene biosynthesis in Gossypium species.

PMID- 29364831
TI  - Exploring the Psoriatic Arthritis Proteome in Search of Novel Biomarkers.
AB  - Psoriatic arthritis (PsA) is an inflammatory arthritis which develops in up to
      one-third of patients suffering from the cutaneous disorder, psoriasis. The
      complex and heterogeneous nature of PsA renders it difficult to diagnose, leading
      to poor outcomes and, therefore, warrants an examination into soluble biomarkers,
      which may facilitate early detection of the disease. Protein biomarkers are a
      dynamic resource of pathophysiological information able to provide an immediate
      reflection of pathological changes caused by disease. Investigations of the serum
      and synovial fluid of PsA patients has provided new insights into the molecular
      basis of this disease and led to the identification of sensitive diagnostic and
      prognostic biomarkers. The collection of novel PsA biomarkers identified through
      proteomic studies has been reviewed below.

PMID- 29364832
TI  - Dielectric, Piezoelectric, and Vibration Properties of the LiF-Doped
      (Ba0.95Ca0.05)(Ti0.93Sn0.07)O3 Lead-Free Piezoceramic Sheets.
AB  - By the conventional solid state reaction method, a small amount of lithium
      fluoride (LiF) was used as the sintering promoter to improve the sintering and
      piezoelectric characteristics of (Ba0.95Ca0.05)(Ti0.93Sn0.07)O3 (BCTS) lead-free
      piezoceramic sheets. Using X-ray diffraction (XRD) and a scanning electron
      microscope (SEM), the inferences of the crystalline and surface microstructures
      were obtained and analyzed. Then, the impedance analyzer and d33-meter were used
      to measure the dielectric and piezoelectric characteristics. In this study, the
      optimum sintering temperature of the BCTS sheets decreased from 1450  degrees C
      to 1390  degrees C due to LiF doping. For the 0.07 wt % LiF-doped BCTS sheets
      sintered at 1390  degrees C, the piezoelectric constant (d33) is 413 pC/N, the
      electric-mechanical coupling coefficient (kp) is 47.5%, the dielectric loss (tan
      delta) is 3.9%, and the dielectric constant (epsilonr) is 8100, which are all
      close to or even better than that of the pure undoped BCTS ceramics. The Curie
      temperature also improved, from 85  degrees C for pure BCTS to 140  degrees C for
      BCTS-0.07 LiF sheets. Furthermore, by using the vibration system and fixing 1.5 g
      tip mass at the end of the sheets, as the vibration frequency is 20 Hz, the
      proposed piezoelectric ceramic sheets also reveal a good energy harvesting
      performance at the maximum output peak voltage of 4.6 V, which is large enough
      and can be applied in modern low-power electronic products.

PMID- 29364833
TI  - Hydrogels for Hydrophobic Drug Delivery. Classification, Synthesis and
      Applications.
AB  - Hydrogels have been shown to be very useful in the field of drug delivery due to
      their high biocompatibility and ability to sustain delivery. Therefore, the
      tuning of their properties should be the focus of study to optimise their
      potential. Hydrogels have been generally limited to the delivery of hydrophilic
      drugs. However, as many of the new drugs coming to market are hydrophobic in
      nature, new approaches for integrating hydrophobic drugs into hydrogels should be
      developed. This article discusses the possible new ways to incorporate
      hydrophobic drugs within hydrogel structures that have been developed through
      research. This review describes hydrogel-based systems for hydrophobic compound
      delivery included in the literature. The section covers all the main types of
      hydrogels, including physical hydrogels and chemical hydrogels. Additionally,
      reported applications of these hydrogels are described in the subsequent
      sections.

PMID- 29364835
TI  - Effective Capture of Carbon Dioxide Using Hydrated Sodium Carbonate Powders.
AB  - The emission of CO2 has been considered a major cause of greenhouse effects and
      global warming. The current CO2 capture approaches have their own advantages and
      weaknesses. We found that free-flowing hydrated sodium carbonate (Na2CO3) powders
      with 30 wt % water can achieve a very high CO2 sorption capacity of 282 mg/g
      within 60 min and fast CO2 uptake (90% saturation uptake within 16 min). The
      results suggest that the alkaline solution resulting from the dissolution of
      partial Na2CO3 can freely attach onto the hydrated Na2CO3 particles, which
      provides an excellent gas-liquid interface for CO2 capture, leading to
      significantly enhanced CO2 sorption capacity and kinetics.

PMID- 29364834
TI  - Quercetin Suppresses CYR61-Mediated Multidrug Resistance in Human Gastric
      Adenocarcinoma AGS Cells.
AB  - Cysteine-rich angiogenic inducer 61 (CYR61) is an extracellular matrix-associated
      protein involved in survival, tumorigenesis, and drug resistance. Therefore, we
      examined the effects of flavones against CYR61-overexpressing human gastric
      adenocarcinoma AGS (AGS-cyr61) cells, which show remarkable resistance to 5
      fluorouracil (5-FU), adriamycin (ADR), tamoxifen (TAM), paclitaxel (PAC), and
      docetaxel (DOC). Among the tested flavones, quercetin had the lowest 50%
      inhibitory concentration (IC50) and significantly reduced the viability of AGS
      cyr61 cells compared with AGS cells. Quercetin: (1) reduced multidrug resistance
      associated protein 1 and nuclear factor (NF)-kappa B p65 subunit levels; (2)
      reversed multidrug resistance (MDR); (3) inhibited colony formation and induced
      caspase-dependent apoptosis; and (4) suppressed migration and down-regulated
      epithelial-mesenchymal transition-related proteins in AGS-cyr61. Moreover, AGS
      cyr61 cells treated with quercetin concentrations close to the IC50 and
      simultaneously treated with 5-FU or ADR in the sub-lethal range showed strong
      synergism between quercetin and these two drugs. These findings indicate that
      CYR61 is a potential regulator of drug resistance and that quercetin may be a
      novel agent for improving the efficacy of anticancer drugs in AGS-cyr61 cells.

PMID- 29364836
TI  - A Stretchable Alternating Current Electroluminescent Fiber.
AB  - Flexible, stretchable electroluminescent fibers are of significance to meet the
      escalating requirements of increasing complexity and multifunctionality of smart
      electronics. We report a stretchable alternating current electroluminescent
      (ACEL) fiber by a low-cost and all solution-processed scalable process. The ACEL
      fiber provides high stretchability, decent light-emitting performance, with
      excellent stability and nearly zero hysteresis. It can be stretched up to 80%
      strain. Our ACEL fiber device maintained a stable luminance for over 6000 stretch
      release cycles at 50% strain. The mechanical stretchability and optical stability
      of our ACEL fiber device provides new possibilities towards next-generation
      stretchable displays, electronic textiles, advanced biomedical imaging and
      lighting, conformable visual readouts in arbitrary shapes, and novel health
      monitoring devices.

PMID- 29364837
TI  - Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The "La Cittadina
      Fondazione" Experience.
AB  - Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in
      human radiotherapy, which allows a high dose to be delivered to tumor volumes and
      low doses to the surrounding organs at risk (OAR). Veterinary clinics takes
      advantage of this feature due to the small target volumes and distances between
      the target and the OAR. Sparing the OAR permits dose escalation, and
      hypofractionation regimens reduce the number of treatment sessions with a simpler
      manageability in the veterinary field. Multimodal volumes definition is mandatory
      for the small volumes involved and a positioning device precisely reproducible
      with a setup confirmation is needed before each session for avoiding missing the
      target. Additionally, the elaborate treatment plan must pursue hard constraints
      and objectives, and its feasibility must be evaluated with a per patient quality
      control. The aim of this work is to report results with regard to brain
      meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal
      tumors with vascular invasion and rabbit thymomas, in comparison with literature
      to determine if VMAT is a safe and viable alternative to surgery or chemotherapy
      alone, or as an adjuvant therapy in pets.

PMID- 29364838
TI  - Informing Efforts to Develop Nitroreductase for Amine Production.
AB  - Nitroreductases (NRs) hold promise for converting nitroaromatics to aromatic
      amines. Nitroaromatic reduction rate increases with Hammett substituent constant
      for NRs from two different subgroups, confirming substrate identity as a key
      determinant of reactivity. Amine yields were low, but compounds yielding amines
      tend to have a large pi system and electron withdrawing substituents. Therefore,
      we also assessed the prospects of varying the enzyme. Several different subgroups
      of NRs include members able to produce aromatic amines. Comparison of four NR
      subgroups shows that they provide contrasting substrate binding cavities with
      distinct constraints on substrate position relative to the flavin. The unique
      architecture of the NR dimer produces an enormous contact area which we propose
      provides the stabilization needed to offset the costs of insertion of the active
      sites between the monomers. Thus, we propose that the functional diversity
      included in the NR superfamily stems from the chemical versatility of the flavin
      cofactor in conjunction with a structure that permits tremendous active site
      variability. These complementary properties make NRs exceptionally promising
      enzymes for development for biocatalysis in prodrug activation and conversion of
      nitroaromatics to valuable aromatic amines. We provide a framework for
      identifying NRs and substrates with the greatest potential to advance.

PMID- 29364839
TI  - The Functional Amyloid Curli Protects Escherichia coli against Complement
      Mediated Bactericidal Activity.
AB  - Escherichia coli strains may be beneficial or pathogenic. Many E. coli strains
      that cause human disease, especially those responsible for bacteremia and sepsis,
      express virulence factors that impart resistance to the complement system. The
      bacterial amyloid curli functions in bacterial adherence and enhances the
      formation of biofilms. Survival of curli-producing parental and curli-deficient
      mutant E. coli in the context of a human complement response was evaluated using
      an in vivo murine model of bacteremia. Results showed that curli production
      enhanced E. coli survival, which suggests that curli defends against complement
      mediated killing. This observation was supported by the results of in vitro
      assays comparing bacterial survival in human serum. Experiments in which the
      classical or alternative complement pathways were blocked indicated that the
      classical pathway is the major contributor to complement activation and that
      curli inhibits this activity. Our analyses indicate that curli does not appear to
      play a role in protecting E. coli against alternative pathway complement
      activation. We found that curli increases binding of E. coli cells to complement
      component Complement component 1q (C1q) but does not affect Complement component
      3b (C3b) binding. We conclude that curli defends E. coli against complement
      mediated killing via inhibition of the classical complement pathway.

PMID- 29364840
TI  - Suppressing the Photocatalytic Activity of TiO2 Nanoparticles by Extremely Thin
      Al2O3 Films Grown by Gas-Phase Deposition at Ambient Conditions.
AB  - This work investigated the suppression of photocatalytic activity of titanium
      dioxide (TiO2) pigment powders by extremely thin aluminum oxide (Al2O3) films
      deposited via an atomic-layer-deposition-type process using trimethylaluminum
      (TMA) and H2O as precursors. The deposition was performed on multiple grams of
      TiO2 powder at room temperature and atmospheric pressure in a fluidized bed
      reactor, resulting in the growth of uniform and conformal Al2O3 films with
      thickness control at sub-nanometer level. The as-deposited Al2O3 films exhibited
      excellent photocatalytic suppression ability. Accordingly, an Al2O3 layer with a
      thickness of 1 nm could efficiently suppress the photocatalytic activities of
      rutile, anatase, and P25 TiO2 nanoparticles without affecting their bulk optical
      properties. In addition, the influence of high-temperature annealing on the
      properties of the Al2O3 layers was investigated, revealing the possibility of
      achieving porous Al2O3 layers. Our approach demonstrated a fast, efficient, and
      simple route to coating Al2O3 films on TiO2 pigment powders at the multigram
      scale, and showed great potential for large-scale production development.

PMID- 29364841
TI  - Phytochemical and Pharmacological Properties of Capparis spinosa as a Medicinal
      Plant.
AB  - Over the past decades, there has been increasing attention on polyphenol-rich
      foods including fruits and vegetables on human health. Polyphenols have been
      shown to possess some potential beneficial effects on human health and they are
      widely found in foods consumed by populations worldwide. Capparis spinosa (C.
      spinosa) is an important source of different secondary metabolites of interest to
      humankind. The traditional therapeutic applications of C. spinosa have been
      reported in Ancient Romans. Numerous bioactive phytochemical constituents have
      been isolated and identified from different parts (aerial parts, roots and seeds)
      of C. spinosa which are responsible alone or in combination for its various
      pharmacological activities. Therefore, this paper is a review of publications on
      the phytochemical and pharmacological properties of C. spinosa. There is
      insufficient evidence to suggest that C. spinosa or its extracts are able to
      improve the biomarkers of cardiovascular disease and diabetes. However, these
      studies used different parts of C. spinosa plant, methods of preparation and
      types of solvents, which cause the evaluation of activity of C. spinosa difficult
      and involve quite heterogeneous data. There is also evidence, although limited,
      to suggest benefits of C. spinosa in improving human health. Therefore, the
      relationship between C. spinosa and improved human health outcomes requires
      further study.

PMID- 29364844
TI  - Application of High-Density Electropulsing to Improve the Performance of Metallic
      Materials: Mechanisms, Microstructure and Properties.
AB  - The technology of high-density electropulsing has been applied to increase the
      performance of metallic materials since the 1990s and has shown significant
      advantages over traditional heat treatment in many aspects. However, the
      microstructure changes in electropulsing treatment (EPT) metals and alloys have
      not been fully explored, and the effects vary significantly on different
      material. When high-density electrical pulses are applied to metals and alloys,
      the input of electric energy and thermal energy generally leads to structural
      rearrangements, such as dynamic recrystallization, dislocation movements and
      grain refinement. The enhanced mechanical properties of the metals and alloys
      after high-density electropulsing treatment are reflected by the significant
      improvement of elongation. As a result, this technology holds great promise in
      improving the deformation limit and repairing cracks and defects in the plastic
      processing of metals. This review summarizes the effect of high-density
      electropulsing treatment on microstructural properties and, thus, the enhancement
      in mechanical strength, hardness and corrosion performance of metallic materials.
      It is noteworthy that the change of some properties can be related to the
      structure state before EPT (quenched, annealed, deformed or others). The
      mechanisms for the microstructural evolution, grain refinement and formation of
      oriented microstructures of different metals and alloys are presented. Future
      research trends of high-density electrical pulse technology for specific metals
      and alloys are highlighted.

PMID- 29364845
TI  - High-Quality GaSe Single Crystal Grown by the Bridgman Method.
AB  - A high-quality GaSe single crystal was grown by the Bridgman method. The X-ray
      rocking curve for the studied GaSe sample is symmetric and the Full Width at Half
      Maximum (FWHM) is only 46 arcs, which is the smallest value ever reported for
      GaSe crystals. The IR-transmittance is about 66% in the range from 500 to 4000 cm
      1. The photoluminescence spectrum at 9.2 K shows a symmetric and sharp excition
      peak in 2.1046 eV. The results indicate that the as-grown GaSe crystal is of high
      crystalline quality. The as-grown epsilon -GaSe crystal has a p-type conductance
      with the resistivity of 103 Omega/cm, and the Hall mobility is ~25 cm2 V-1 s-1.
      Few-layer GaSe crystals were prepared through mechanical exfoliation from this
      high-quality crystal sample. Few-layer GaSe-based photodetectors were fabricated,
      which exhibit an on/off ratio of 104, a field-effect differential mobility of 0.4
      cm2 V-1 s-1, and have a fast response time less than 60 ms under light
      illumination.

PMID- 29364843
TI  - Proteomic Analyses of the Unexplored Sea Anemone Bunodactis verrucosa.
AB  - Cnidarian toxic products, particularly peptide toxins, constitute a promising
      target for biomedicine research. Indeed, cnidarians are considered as the largest
      phylum of generally toxic animals. However, research on peptides and toxins of
      sea anemones is still limited. Moreover, most of the toxins from sea anemones
      have been discovered by classical purification approaches. Recently, high
      throughput methodologies have been used for this purpose but in other Phyla.
      Hence, the present work was focused on the proteomic analyses of whole-body
      extract from the unexplored sea anemone Bunodactis verrucosa. The proteomic
      analyses applied were based on two methods: two-dimensional gel electrophoresis
      combined with MALDI-TOF/TOF and shotgun proteomic approach. In total, 413
      proteins were identified, but only eight proteins were identified from gel-based
      analyses. Such proteins are mainly involved in basal metabolism and biosynthesis
      of antibiotics as the most relevant pathways. In addition, some putative toxins
      including metalloproteinases and neurotoxins were also identified. These findings
      reinforce the significance of the production of antimicrobial compounds and
      toxins by sea anemones, which play a significant role in defense and feeding. In
      general, the present study provides the first proteome map of the sea anemone B.
      verrucosa stablishing a reference for future studies in the discovery of new
      compounds.

PMID- 29364846
TI  - Synthesis and Optical Properties of Near-Infrared meso-Phenyl-Substituted
      Symmetric Heptamethine Cyanine Dyes.
AB  - Heptamethine cyanine dyes are a class of near infrared fluorescence (NIRF) probes
      of great interest in bioanalytical and imaging applications due to their
      modifiability, allowing them to be tailored for particular applications.
      Generally, modifications at the meso-position of these dyes are achieved through
      Suzuki-Miyaura C-C coupling and SRN1 nucleophilic substitution of the chlorine
      atom at the meso-position of the dye. Herein, a series of 15 meso phenyl
      substituted heptamethine cyanines was synthesized utilizing a modified dianil
      linker. Their optical properties, including molar absorptivity, fluorescence,
      Stokes shift, and quantum yield were measured. The HSA binding affinities of two
      representative compounds were measured and compared to that of a series of
      trimethine cyanines previously synthesized by our lab. The results indicate that
      the binding of these compounds to HSA is not only dependent on hydrophobicity,
      but may also be dependent on steric interferences in the binding site and
      structural dynamics of the NIRF compounds.

PMID- 29364847
TI  - Sensing Performance Analysis on Quartz Tuning Fork-Probe at the High Order
      Vibration Mode for Multi-Frequency Scanning Probe Microscopy.
AB  - Multi-frequency scanning near-field optical microscopy, based on a quartz tuning
      fork-probe (QTF-p) sensor using the first two orders of in-plane bending
      symmetrical vibration modes, has recently been developed. This method can
      simultaneously achieve positional feedback (based on the 1st in-plane mode called
      the low mode) and detect near-field optically induced forces (based on the 2nd in
      plane mode called the high mode). Particularly, the high mode sensing performance
      of the QTF-p is an important issue for characterizing the tip-sample interactions
      and achieving higher resolution microscopic imaging but the related researches
      are insufficient. Here, we investigate the vibration performance of QTF-p at high
      mode based on the experiment and finite element method. The frequency spectrum
      characteristics are obtained by our homemade laser Doppler vibrometer system. The
      effects of the properties of the connecting glue layer and the probe features on
      the dynamic response of the QTF-p sensor at the high mode are investigated for
      optimization design. Finally, compared with the low mode, an obvious improvement
      of quality factor, of almost 50%, is obtained at the high mode. Meanwhile, the
      QTF-p sensor has a high force sensing sensitivity and a large sensing range at
      the high mode, indicating a broad application prospect for force sensing.

PMID- 29364842
TI  - Natural Dietary Pigments: Potential Mediators against Hepatic Damage Induced by
      Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs.
AB  - Over-the-counter (OTC) analgesics are among the most widely prescribed and
      purchased drugs around the world. Most analgesics, including non-steroidal anti
      inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The
      hepatocytes are responsible for drug metabolism and detoxification. Cytochrome
      P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account
      for ~75% of the metabolism of clinically used drugs and other xenobiotics. These
      metabolic reactions eliminate potentially toxic compounds but, paradoxically,
      also result in the generation of toxic or carcinogenic metabolites. Cumulative or
      overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either
      directly or indirectly after their biotransformation. ALF is the result of
      massive death of hepatocytes induced by oxidative stress. There is an increased
      interest in the use of natural dietary products as nutritional supplements and/or
      medications to prevent or cure many diseases. The therapeutic activity of natural
      products may be associated with their antioxidant capacity, although additional
      mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary
      antioxidants such as flavonoids, betalains and carotenoids play a preventive role
      against OTC analgesics-induced ALF. In this review, we will summarize the
      pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its
      prevention and therapy.

PMID- 29364848
TI  - An EEG-Based Person Authentication System with Open-Set Capability Combining Eye
      Blinking Signals.
AB  - The electroencephalogram (EEG) signal represents a subject's specific brain
      activity patterns and is considered as an ideal biometric given its superior
      forgery prevention. However, the accuracy and stability of the current EEG-based
      person authentication systems are still unsatisfactory in practical application.
      In this paper, a multi-task EEG-based person authentication system combining eye
      blinking is proposed, which can achieve high precision and robustness. Firstly,
      we design a novel EEG-based biometric evoked paradigm using self- or non-self
      face rapid serial visual presentation (RSVP). The designed paradigm could obtain
      a distinct and stable biometric trait from EEG with a lower time cost. Secondly,
      the event-related potential (ERP) features and morphological features are
      extracted from EEG signals and eye blinking signals, respectively. Thirdly,
      convolutional neural network and back propagation neural network are severally
      designed to gain the score estimation of EEG features and eye blinking features.
      Finally, a score fusion technology based on least square method is proposed to
      get the final estimation score. The performance of multi-task authentication
      system is improved significantly compared to the system using EEG only, with an
      increasing average accuracy from 92.4% to 97.6%. Moreover, open-set
      authentication tests for additional imposters and permanence tests for users are
      conducted to simulate the practical scenarios, which have never been employed in
      previous EEG-based person authentication systems. A mean false accepted rate
      (FAR) of 3.90% and a mean false rejected rate (FRR) of 3.87% are accomplished in
      open-set authentication tests and permanence tests, respectively, which
      illustrate the open-set authentication and permanence capability of our systems.

PMID- 29364849
TI  - Multiple Attribute Group Decision-Making Methods Based on Trapezoidal Fuzzy Two
      Dimensional Linguistic Partitioned Bonferroni Mean Aggregation Operators.
AB  - In this paper, we investigate multiple attribute group decision making (MAGDM)
      problems where decision makers represent their evaluation of alternatives by
      trapezoidal fuzzy two-dimensional uncertain linguistic variable. To begin with,
      we introduce the definition, properties, expectation, operational laws of
      trapezoidal fuzzy two-dimensional linguistic information. Then, to improve the
      accuracy of decision making in some case where there are a sort of
      interrelationship among the attributes, we analyze partition Bonferroni mean
      (PBM) operator in trapezoidal fuzzy two-dimensional variable environment and
      develop two operators: trapezoidal fuzzy two-dimensional linguistic partitioned
      Bonferroni mean (TF2DLPBM) aggregation operator and trapezoidal fuzzy two
      dimensional linguistic weighted partitioned Bonferroni mean (TF2DLWPBM)
      aggregation operator. Furthermore, we develop a novel method to solve MAGDM
      problems based on TF2DLWPBM aggregation operator. Finally, a practical example is
      presented to illustrate the effectiveness of this method and analyses the impact
      of different parameters on the results of decision-making.

PMID- 29364850
TI  - Protective Immunity Induced by DNA Vaccination against Ranavirus Infection in
      Chinese Giant Salamander Andrias davidianus.
AB  - Andrias davidianus ranavirus (ADRV) is an emerging viral pathogen that causes
      severe systemic hemorrhagic disease in Chinese giant salamanders. There is an
      urgent need for developing an effective vaccine against this fatal disease. In
      this study, DNA vaccines containing the ADRV 2L gene (pcDNA-2L) and the 58L gene
      (pcDNA-58L) were respectively constructed, and their immune protective effects
      were evaluated in Chinese giant salamanders. In vitro and in vivo expression of
      the vaccine plasmids were confirmed in transfected cells and muscle tissues of
      vaccinated Chinese giant salamanders by using immunoblot analysis or RT-PCR.
      Following ADRV challenge, the Chinese giant salamanders vaccinated with pcDNA-2L
      showed a relative percent survival (RPS) of 66.7%, which was significant higher
      than that in Chinese giant salamanders immunized with pcDNA-58L (RPS of 3.3%).
      Moreover, the specific antibody against ADRV was detected in Chinese giant
      salamanders vaccinated with pcDNA-2L at 14 and 21 days post-vaccination by
      indirect enzyme-linked immunosorbent assay (ELISA). Transcriptional analysis
      revealed that the expression levels of immune-related genes including type I
      interferon (IFN), myxovirus resistance (Mx), major histocompatibility complex
      class IA (MHCIA), and immunoglobulin M (IgM) were strongly up-regulated after
      vaccination with pcDNA-2L. Furthermore, vaccination with pcDNA-2L significantly
      suppressed the virus replication, which was seen by a low viral load in the
      spleen of Chinese giant salamander survivals after ADRV challenge. These results
      indicated that pcDNA-2L could induce a significant innate immune response and an
      adaptive immune response involving both humoral and cell-mediated immunity that
      conferred effective protection against ADRV infection, and might be a potential
      vaccine candidate for controlling ADRV disease in Chinese giant salamanders.

PMID- 29364851
TI  - Optimum Water Quality Monitoring Network Design for Bidirectional River Systems.
AB  - Affected by regular tides, bidirectional water flows play a crucial role in
      surface river systems. Using optimization theory to design a water quality
      monitoring network can reduce the redundant monitoring nodes as well as save the
      costs for building and running a monitoring network. A novel algorithm is
      proposed to design an optimum water quality monitoring network for tidal rivers
      with bidirectional water flows. Two optimization objectives of minimum pollution
      detection time and maximum pollution detection probability are used in our
      optimization algorithm. We modify the Multi-Objective Particle Swarm Optimization
      (MOPSO) algorithm and develop new fitness functions to calculate pollution
      detection time and pollution detection probability in a discrete manner. In
      addition, the Storm Water Management Model (SWMM) is used to simulate hydraulic
      characteristics and pollution events based on a hypothetical river system studied
      in the literature. Experimental results show that our algorithm can obtain a
      better Pareto frontier. The influence of bidirectional water flows to the network
      design is also identified, which has not been studied in the literature. Besides
      that, we also find that the probability of bidirectional water flows has no
      effect on the optimum monitoring network design but slightly changes the mean
      pollution detection time.

PMID- 29364852
TI  - Workers' Exposure to Nano-Objects with Different Dimensionalities in R&D
      Laboratories: Measurement Strategy and Field Studies.
AB  - With the increasing interest in the potential benefits of nanotechnologies,
      concern is still growing that they may present emerging risks for workers.
      Various strategies have been developed to assess the exposure to nano-objects and
      their agglomerates and aggregates (NOAA) in the workplace, integrating different
      aerosol measurement instruments and taking into account multiple parameters that
      may influence NOAA toxicity. The present study proposes a multi-metric approach
      for measuring and sampling NOAA in the workplace, applied to three case studies
      in laboratories each dedicated to materials with different shapes and
      dimensionalities: graphene, nanowires, and nanoparticles. The study is part of a
      larger project with the aim of improving risk management tools in nanomaterials
      research laboratories. The harmonized methodology proposed by the Organization
      for Economic Cooperation and Development (OECD) has been applied, including
      information gathering about materials and processes, measurements with easy-to
      use and hand-held real-time devices, air sampling with personal samplers, and off
      line analysis using scanning electron microscopy. Significant values beyond which
      an emission can be attributed to the NOAA production process were identified by
      comparison of the particle number concentration (PNC) time series and the
      corresponding background levels in the three laboratories. We explored the
      relations between background PNC and microclimatic parameters. Morphological and
      elemental analysis of sampled filters was done to identify possible emission
      sources of NOAA during the production processes: rare particles, spherical, with
      average diameter similar to the produced NOAA were identified in the
      nanoparticles laboratory, so further investigation is recommended to confirm the
      potential for worker exposure. In conclusion, the information obtained should
      provide a valuable basis for improving risk management strategies in the
      laboratory at work.

PMID- 29364853
TI  - Examining the Impact of Maternal Individual Features on Children's Behavioral
      Problems in Adoptive Families: The Role of Maternal Temperament and
      Neurobiological Markers.
AB  - The first year after adoption constitutes a sensitive period for both
      strengthening the new emotional bond in the family and checking its appropriate
      development by adoption services. A key variable for children's catch-up are
      adoptive parents' socioemotional and individual features. The aim of this study
      is to investigate links between adoptive mothers' individual features and
      behavioral problems in their children in the first year after adoption placement,
      by testing the moderating role of both age at adoption and maternal genetic
      polymorphisms. Seventy-eight adoptive mothers completed temperament and genetic
      measures. Mothers showed a specific pattern of interaction between basic
      temperament traits and genetic markers in their assessment of children's
      behavioral problems; dopamine D4 receptor gene and children's age at adoption are
      two moderators in the association in which mothers' temperament was affecting the
      evaluation of their children's behavioral problems. Findings highlight a still
      undervalued area of parenting resources in the process of post-institutionalized
      children's catch-up after adoption placement, by showing how individual features
      count in the commonly measured variable of children's behavioral and emotional
      problems. This could help in orienting identification and choice of key variables
      for family assessment after adoption placement, thus contributing in fostering
      children's healthy development.

PMID- 29364854
TI  - Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia
      Injury: A Comparison between IGL-1 and HTK.
AB  - Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK)
      preservation solutions are regularly used in clinical for liver transplantation
      besides University of Wisconsin (UW) solution and Celsior. Several clinical
      trials and experimental works have been carried out comparing all the solutions,
      however the comparative IGL-1 and HTK appraisals are poor; especially when they
      deal with the underlying protection mechanisms of the fatty liver graft during
      cold storage. Fatty livers from male obese Zucker rats were conserved for 24 h at
      4  degrees C in IGL-1 or HTK preservation solutions. After organ recovery and
      rinsing of fatty liver grafts with Ringer Lactate solution, we measured the
      changes in mechanistic target of rapamycin (mTOR) signaling activation, liver
      autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers
      (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the
      prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT),
      histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal
      microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked
      reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with
      significant increased cyto-protective autophagy and prevention of liver
      apoptosis, including inflammatory cytokines such as HMGB1. Together, our results
      revealed that IGL-1 preservation solution better protected fatty liver grafts
      against cold ischemia damage than HTK solution. IGL-1 protection was associated
      with a reduced liver damage, higher induced autophagy and decreased apoptosis.
      All these effects would contribute to limit the subsequent extension of
      reperfusion injury after graft revascularization in liver transplantation
      procedures.

PMID- 29364856
TI  - New Fault Recognition Method for Rotary Machinery Based on Information Entropy
      and a Probabilistic Neural Network.
AB  - Feature recognition and fault diagnosis plays an important role in equipment
      safety and stable operation of rotating machinery. In order to cope with the
      complexity problem of the vibration signal of rotating machinery, a feature
      fusion model based on information entropy and probabilistic neural network is
      proposed in this paper. The new method first uses information entropy theory to
      extract three kinds of characteristics entropy in vibration signals, namely,
      singular spectrum entropy, power spectrum entropy, and approximate entropy. Then
      the feature fusion model is constructed to classify and diagnose the fault
      signals. The proposed approach can combine comprehensive information from
      different aspects and is more sensitive to the fault features. The experimental
      results on simulated fault signals verified better performances of our proposed
      approach. In real two-span rotor data, the fault detection accuracy of the new
      method is more than 10% higher compared with the methods using three kinds of
      information entropy separately. The new approach is proved to be an effective
      fault recognition method for rotating machinery.

PMID- 29364855
TI  - Comparative Digital Gene Expression Analysis of Tissue-Cultured Plantlets of
      Highly Resistant and Susceptible Banana Cultivarsin Response to Fusarium
      oxysporum.
AB  - Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is one of
      the most destructive soil-borne diseases. In this study, young tissue-cultured
      plantlets of banana (Musa spp. AAA) cultivars differing in Foc susceptibility
      were used to reveal their differential responses to this pathogen using digital
      gene expression (DGE). Data were evaluated by various bioinformatic tools (Venn
      diagrams, gene ontology (GO) annotation and Kyoto encyclopedia of genes and
      genomes (KEGG) pathway analyses) and immunofluorescence labelling method to
      support the identification of gene candidates determining the resistance of
      banana against Foc. Interestingly, we have identified MaWRKY50 as an important
      gene involved in both constitutive and induced resistance. We also identified new
      genes involved in the resistance of banana to Foc, including several other
      transcription factors (TFs), pathogenesis-related (PR) genes and some genes
      related to the plant cell wall biosynthesis or degradation (e.g.,
      pectinesterases, beta-glucosidases, xyloglucan endotransglucosylase/hydrolase and
      endoglucanase). The resistant banana cultivar shows activation of PR-3 and PR-4
      genes as well as formation of different constitutive cell barriers to restrict
      spreading of the pathogen. These data suggest new mechanisms of banana resistance
      to Foc.

PMID- 29364857
TI  - Managing Exposure to Benzene and Total Petroleum Hydrocarbons at Two Oil
      Refineries 1977-2014.
AB  - Air concentrations of and inhalation exposure to total petroleum hydrocarbons
      (TPH) and benzene was monitored separately at two oil refineries from 1977 to
      2014. Prevention policies and control measures that may explain changes were
      surveyed. The aim was to evaluate how the application of of Occupational Health
      and Safety Assessment Series OHSAS 18001.04 principles as well as Environmental
      protection Agency EPA and European Oil Company Organisation for Environment,
      Health and Safety CONCAWE practices have influenced air concentrations. Benzene
      air concentrations declined in 11 of 17 units, six of which were associated with
      declining exposures. Benzene air concentrations declined across all units on
      average by 46%. This amounts to an average yearly decline of 1.7%. TPH air
      concentrations declined in 10 of 17 units, seven of which were associated with
      declining exposures. The average decline in TPH air concentrations was 49%,
      corresponding to 1.3% per year. As a result, average working day exposure in 10
      of 17 units have declined significantly and today, benzene and TPH exposure in
      most units are well below 10% of the current Occupational Exposure Limit
      (OEL8h:s). A decline in air concentrations have coincided with consistent
      implementation of control measures. Such measures include on-line monitoring of
      leaks; benzene recovery; floating container roofs; improved valves and seals;
      hermetic pumps; recovery of loading gases and instalment of torches in terminals;
      cutback in coke combustion; a new production line spanning directly from the dock
      to aromatics production; and recovery of loading gases in the doc. Other tools in
      exposure management include personal leak monitors, on-line measurements,
      monitoring campaigns, risk assessment, and availability and user training of
      protective equipment. However, improvements are still needed. Hydrocarbon or
      benzene air concentrations have not declined in 8 of 17 units, in some of which
      concentrations exceed 10% of the relevant OEL8h value. In addition, for benzene
      even 10% of the current OEL, 0.1 ppm, might still possess a risk. With this in
      mind, methods to estimate exposure at the refineries need to be improved to
      enable measuring benzene concentrations <0.1 ppm. Shut downs of the refinery have
      been associated with peaks in exposure concentrations. Consequently, effort
      should be placed on safe working methods pertaining to shutdowns. Also, the
      connection and detachment of hoses continues to be problematic from the point of
      view of controlling exposure.

PMID- 29364859
TI  - Nanofiltration and Tight Ultrafiltration Membranes for the Recovery of
      Polyphenols from Agro-Food By-Products.
AB  - Pressure-driven membrane-based technologies represent a valid approach to reduce
      the environmental pollution of several agro-food by-products. Recently, in
      relation to the major interest for natural compounds with biological activities,
      their use has been also addressed to the recovery, separation and fractionation
      of phenolic compounds from such by-products. In particular, tight ultrafiltration
      (UF) and nanolfiltration (NF) membranes have been recognized for their capability
      to recover phenolic compounds from several types of agro-food by-products. The
      separation capability of these membranes, as well as their productivity, depends
      on multiple factors such as membrane material, molecular weight cut-off (MWCO)
      and operating conditions (e.g., pressure, temperature, feed flow rate, volume
      reduction factor, etc.). This paper aims at providing a critical overview of the
      influence of these parameters on the recovery of phenolic compounds from agro
      food by-products by using tight UF and NF membranes. The literature data are
      analyzed and discussed in relation to separation processes, molecule properties,
      membrane characteristics and other phenomena occurring in the process. Current
      extraction methodologies of phenolic compounds from raw materials are also
      introduced in order to drive the implementation of integrated systems for the
      production of actractive phenolic formulations of potential interest as food
      antioxidants.

PMID- 29364860
TI  - Exploring the Framing of Animal Farming and Meat Consumption: On the Diversity of
      Topics Used and Qualitative Patterns in Selected Demographic Contexts.
AB  - In various contexts, people talk about animal farming and meat consumption using
      different arguments to construct and justify their (non-)acceptability. This
      article presents the results of an in-depth qualitative inquiry into the content
      of and contextual patterns in the everyday-life framing regarding this issue,
      performed among consumers in various settings in two extremes in the European
      sphere: the Netherlands and Turkey. We describe the methodological steps of
      collecting, coding, and organizing the variety of encountered framing topics, as
      well as our search for symbolic convergence in groups of consumers from different
      selected demographic contexts (country, urban-rural areas, gender, age, and
      education level). The framing of animal farming and meat consumption in everyday
      life is not a simple one-issue rational display of facts; people referred to a
      vast range of topics in the categories knowledge, convictions, pronounced
      behaviour, values, norms, interests, and feelings. Looking at framing in relation
      to the researched demographic contexts, most patterns were found on the level of
      topics; symbolic convergence in lines of reasoning and composite framing was less
      prominent in groups based on single demographic contexts than anticipated. An
      explanation for this lies in the complexity of frame construction, happening in
      relation with multiple interdependent contextual features.

PMID- 29364861
TI  - Soft Material-Enabled, Flexible Hybrid Electronics for Medicine, Healthcare, and
      Human-Machine Interfaces.
AB  - Flexible hybrid electronics (FHE), designed in wearable and implantable
      configurations, have enormous applications in advanced healthcare, rapid disease
      diagnostics, and persistent human-machine interfaces. Soft, contoured geometries
      and time-dynamic deformation of the targeted tissues require high flexibility and
      stretchability of the integrated bioelectronics. Recent progress in developing
      and engineering soft materials has provided a unique opportunity to design
      various types of mechanically compliant and deformable systems. Here, we
      summarize the required properties of soft materials and their characteristics for
      configuring sensing and substrate components in wearable and implantable devices
      and systems. Details of functionality and sensitivity of the recently developed
      FHE are discussed with the application areas in medicine, healthcare, and machine
      interactions. This review concludes with a discussion on limitations of current
      materials, key requirements for next generation materials, and new application
      areas.

PMID- 29364863
TI  - The AMP-Activated Protein Kinase Homolog Snf1 Concerts Carbon Utilization,
      Conidia Production and the Biosynthesis of Secondary Metabolites in the Taxol
      Producer Pestalotiopsis microspora.
AB  - Highly conserved, the Snf1/AMPK is a central regulator of carbon metabolism and
      energy production in the eukaryotes. However, its function in filamentous fungi
      has not been well established. In this study, we reported functional
      characterization of Snf1/AMPK in the growth, development and secondary metabolism
      in the filamentous fungus Pestalotiopsis microspora. By deletion of the yeast
      SNF1 homolog, we found that it regulated the utilization of carbon sources, e.g.,
      sucrose, demonstrating a conserved function of this kinase in filamentous fungus.
      Importantly, several novel functions of SNF1 were unraveled. For instance, the
      deletion strain displayed remarkable retardation in vegetative growth and
      pigmentation and produced a diminished number of conidia, even in the presence of
      the primary carbon source glucose. Deletion of the gene caused damages in the
      cell wall as shown by its hypersensitivities to Calcofluor white and Congo red,
      suggesting a critical role of Snf1 in maintaining cell wall integrity.
      Furthermore, the mutant strain Deltasnf1 was hypersensitive to stress, e.g.,
      osmotic pressure (1 M sorbitol), drug G418 and heat shock, though the mechanism
      remains to be illustrated. Significantly, disruption of the gene altered the
      production of secondary metabolites. By high-performance liquid chromatography
      (HPLC) profiling, we found that Deltasnf1 barely produced secondary metabolites,
      e.g., the known product pestalotiollide B. This study suggests that Snf1 is a key
      regulator in filamentous fungus Pestalotiopsis microspora concerting carbon
      metabolism and the filamentous growth, conidiation, cell wall integrity, stress
      tolerance and the biosynthesis of secondary metabolites.

PMID- 29364864
TI  - Development and In Vitro Release of Isoniazid and Rifampicin-Loaded Bovine Serum
      Albumin Nanoparticles.
AB  - BACKGROUND Bovine serum albumin nanoparticles loaded with isoniazid and
      rifampicin (INH-RFP-BSA-NPs) were prepared and their release characteristics were
      studied in vitro. MATERIAL AND METHODS The INH-RFP-BSA-NPs were prepared by a
      modified self-emulsion solvent diffusion method, with albumin and polylactic acid
      used as carriers and to form the nanoparticles structure. Transmission electron
      microscopy was used to observe the morphology of the INH-RFP-BSA-NPs. The size
      distribution of the INH-RFP-BSA-NPs were assessed using a submicron particle-size
      analyzer for drug loadings, and the coating rate of the INH-RFP-BSA-NPs was
      measured by high-performance liquid chromatography. A dynamic membrane dialysis
      method was used to study the in vitro release characteristics of the INH-RFP-BSA
      NPs. RESULTS The INH-RFP-BSA-NPs were smooth, sphere-like, relatively uniform in
      size, and well-dispersed, and the average diameter was 60.5+/-4.6 nm. Drug
      loading and entrapment efficiencies were high, at 19.8% and 87.8% for isoniazid,
      respectively, and 20.1% and 98.0% for rifampicin, respectively. Drug release was
      slow and sustained with 97.02% INH cumulative release at 6 days, and full release
      of RFP requiring 5 days. CONCLUSIONS INH-RFP-BSA-NPs exhibit uniform NP diameter,
      good dispersion, high drug loading and encapsulation rates, and have sustained
      release properties.

PMID- 29364865
TI  - Age-dependent susceptibility to reovirus encephalitis in mice is influenced by
      maturation of the type-I interferon response.
AB  - BackgroundInfants and young children are particularly susceptible to viral
      encephalitis; however, the mechanisms are unknown. We determined the age
      dependent contribution of innate and adaptive immune functions to reovirus
      induced encephalitis in mice.MethodsNewborn wild-type mice, 2-20 days of age,
      were inoculated with reovirus or diluent and monitored for mortality, weight
      gain, and viral load. Four- and fifteen-day-old IFNAR-/- and RAG2-/- mice were
      inoculated with reovirus and similarly monitored.ResultsWeight gain was impaired
      in mice inoculated with reovirus at 8 days of age or less. Clinical signs of
      encephalitis were detected in mice inoculated at 10 days of age or less.
      Mortality decreased when mice were inoculated after 6 days of age. Survival was
      <=15% in wild type (WT), RAG2-/-, and IFNAR-/- mice inoculated at 4 days of age.
      All WT mice, 92% of RAG2-/- mice, and only 48% of IFNAR-/- mice survived
      following inoculation at 15 days of age.ConclusionsSusceptibility of mice to
      reovirus-induced disease decreases between 6 and 8 days of age. Enhanced reovirus
      virulence in IFNAR-/- mice relative to WT and RAG2-/- mice inoculated at 15 days
      of age suggests that maturation of the type-I interferon response contributes to
      age-related mortality following reovirus infection.

PMID- 29364862
TI  - Genomic Diversity in the Endosymbiotic Bacterium Rhizobium leguminosarum.
AB  - Rhizobium leguminosarum bv. viciae is a soil alpha-proteobacterium that
      establishes a diazotrophic symbiosis with different legumes of the Fabeae tribe.
      The number of genome sequences from rhizobial strains available in public
      databases is constantly increasing, although complete, fully annotated genome
      structures from rhizobial genomes are scarce. In this work, we report and analyse
      the complete genome of R. leguminosarum bv. viciae UPM791. Whole genome
      sequencing can provide new insights into the genetic features contributing to
      symbiotically relevant processes such as bacterial adaptation to the rhizosphere,
      mechanisms for efficient competition with other bacteria, and the ability to
      establish a complex signalling dialogue with legumes, to enter the root without
      triggering plant defenses, and, ultimately, to fix nitrogen within the host.
      Comparison of the complete genome sequences of two strains of R. leguminosarum
      bv. viciae, 3841 and UPM791, highlights the existence of different symbiotic
      plasmids and a common core chromosome. Specific genomic traits, such as plasmid
      content or a distinctive regulation, define differential physiological
      capabilities of these endosymbionts. Among them, strain UPM791 presents unique
      adaptations for recycling the hydrogen generated in the nitrogen fixation
      process.

PMID- 29364866
TI  - IFN-gamma-dependent epigenetic regulation instructs colitogenic
      monocyte/macrophage lineage differentiation in vivo.
AB  - Colonic macrophages induce pathogenic inflammation against commensal bacteria,
      leading to inflammatory bowel disease (IBD). Although the ontogeny of colonic
      macrophages has been well studied in the past decade, how macrophages gain
      colitogenic properties during the development of colitis is unknown. Using a
      chemically induced colitis model, we showed that accumulated Ly6C+ cells
      consisting of inflammatory monocytes and inflammatory macrophages strongly
      expressed representative colitogenic mediators such as tumor necrosis factor
      alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). The interferon
      gamma-signal transducer and activator of transcription 1 (IFN-gamma-Stat1)
      pathway was required for generating colitogenic macrophages, given that Stat1-/-
      mice had less severe colitis and fewer colitogenic macrophages. Notably, IFN
      gamma induced histone acetylation at the promoter regions of the Tnf and Nos2
      loci in the monocyte and macrophage lineage, indicating that IFN-gamma-dependent
      epigenetic regulation instructs the development of the colitogenic monocyte and
      macrophage lineage in vivo. Collectively, our results provide the essential
      mechanism by which dysregulated colitogenic monocytes/macrophages develop at the
      colon mucosa during inflammation, and suggest a new drug target for treating IBD.

PMID- 29364868
TI  - Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP
      hydrolysis.
AB  - Both mitochondria and lysosomes are essential for maintaining cellular
      homeostasis, and dysfunction of both organelles has been observed in multiple
      diseases. Mitochondria are highly dynamic and undergo fission and fusion to
      maintain a functional mitochondrial network, which drives cellular metabolism.
      Lysosomes similarly undergo constant dynamic regulation by the RAB7 GTPase, which
      cycles from an active GTP-bound state into an inactive GDP-bound state upon GTP
      hydrolysis. Here we have identified the formation and regulation of mitochondria
      lysosome membrane contact sites using electron microscopy, structured
      illumination microscopy and high spatial and temporal resolution confocal live
      cell imaging. Mitochondria-lysosome contacts formed dynamically in healthy
      untreated cells and were distinct from damaged mitochondria that were targeted
      into lysosomes for degradation. Contact formation was promoted by active GTP
      bound lysosomal RAB7, and contact untethering was mediated by recruitment of the
      RAB7 GTPase-activating protein TBC1D15 to mitochondria by FIS1 to drive RAB7 GTP
      hydrolysis and thereby release contacts. Functionally, lysosomal contacts mark
      sites of mitochondrial fission, allowing regulation of mitochondrial networks by
      lysosomes, whereas conversely, mitochondrial contacts regulate lysosomal RAB7
      hydrolysis via TBC1D15. Mitochondria-lysosome contacts thus allow bidirectional
      regulation of mitochondrial and lysosomal dynamics, and may explain the
      dysfunction observed in both organelles in various human diseases.

PMID- 29364870
TI  - A parsec-scale optical jet from a massive young star in the Large Magellanic
      Cloud.
AB  - Highly collimated parsec-scale jets, which are generally linked to the presence
      of an accretion disk, are commonly observed in low-mass young stellar objects. In
      the past two decades, a few of these jets have been directly (or indirectly)
      observed from higher-mass (larger than eight solar masses) young stellar objects,
      adding to the growing evidence that disk-mediated accretion also occurs in high
      mass stars, the formation mechanism of which is still poorly understood. Of the
      observed jets from massive young stars, none is in the optical regime (massive
      young stars are typically highly obscured by their natal material), and none is
      found outside of the Milky Way. Here we report observations of HH 1177, an
      optical ionized jet that originates from a massive young stellar object located
      in the Large Magellanic Cloud. The jet is highly collimated over its entire
      measured length of at least ten parsecs and has a bipolar geometry. The presence
      of a jet indicates ongoing, disk-mediated accretion and, together with the high
      degree of collimation, implies that this system is probably formed through a
      scaled-up version of the formation mechanism of low-mass stars. We conclude that
      the physics that govern jet launching and collimation is independent of stellar
      mass.

PMID- 29364869
TI  - The honeycomb maze provides a novel test to study hippocampal-dependent spatial
      navigation.
AB  - Here we describe the honeycomb maze, a behavioural paradigm for the study of
      spatial navigation in rats. The maze consists of 37 platforms that can be raised
      or lowered independently. Place navigation requires an animal to go to a goal
      platform from any of several start platforms via a series of sequential choices.
      For each, the animal is confined to a raised platform and allowed to choose
      between two of the six adjacent platforms, the correct one being the platform
      with the smallest angle to the goal-heading direction. Rats learn rapidly and
      their choices are influenced by three factors: the angle between the two choice
      platforms, the distance from the goal, and the angle between the correct platform
      and the direction of the goal. Rats with hippocampal damage are impaired in
      learning and their performance is affected by all three factors. The honeycomb
      maze represents a marked improvement over current spatial navigation tests, such
      as the Morris water maze, because it controls the choices of the animal at each
      point in the maze, provides the ability to assess knowledge of the goal direction
      from any location, enables the identification of factors influencing task
      performance and provides the possibility for concomitant single-cell recording.

PMID- 29364867
TI  - Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.
AB  - The poor correlation of mutational landscapes with phenotypes limits our
      understanding of the pathogenesis and metastasis of pancreatic ductal
      adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a
      critical role in PDAC biology and phenotypic diversification. We find an increase
      in gene dosage of mutant KRAS in human PDAC precursors, which drives both early
      tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To
      overcome the limitations posed to gene dosage studies by the stromal richness of
      PDAC, we have developed large cell culture resources of metastatic mouse PDAC.
      Integration of cell culture genomes, transcriptomes and tumour phenotypes with
      functional studies and human data reveals additional widespread effects of
      oncogenic dosage variation on cell morphology and plasticity, histopathology and
      clinical outcome, with the highest KrasMUT levels underlying aggressive
      undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc,
      Yap1 or Nfkb2), which collaborate with heterozygous KrasMUT in driving
      tumorigenesis, but have lower metastatic potential. Mechanistically, different
      oncogenic gains and dosages evolve along distinct evolutionary routes, licensed
      by defined allelic states and/or combinations of hallmark tumour suppressor
      alterations (Cdkn2a, Trp53, Tgfbeta-pathway). Thus, evolutionary constraints and
      contingencies direct oncogenic dosage gain and variation along defined routes to
      drive the early progression of PDAC and shape its downstream biology. Our study
      uncovers universal principles of Ras-driven oncogenesis that have potential
      relevance beyond pancreatic cancer.

PMID- 29364871
TI  - The genome of Schmidtea mediterranea and the evolution of core cellular
      mechanisms.
AB  - The planarian Schmidtea mediterranea is an important model for stem cell research
      and regeneration, but adequate genome resources for this species have been
      lacking. Here we report a highly contiguous genome assembly of S. mediterranea,
      using long-read sequencing and a de novo assembler (MARVEL) enhanced for low
      complexity reads. The S. mediterranea genome is highly polymorphic and
      repetitive, and harbours a novel class of giant retroelements. Furthermore, the
      genome assembly lacks a number of highly conserved genes, including critical
      components of the mitotic spindle assembly checkpoint, but planarians maintain
      checkpoint function. Our genome assembly provides a key model system resource
      that will be useful for studying regeneration and the evolutionary plasticity of
      core cell biological mechanisms.

PMID- 29364872
TI  - The axolotl genome and the evolution of key tissue formation regulators.
AB  - Salamanders serve as important tetrapod models for developmental, regeneration
      and evolutionary studies. An extensive molecular toolkit makes the Mexican
      axolotl (Ambystoma mexicanum) a key representative salamander for molecular
      investigations. Here we report the sequencing and assembly of the 32-gigabase
      pair axolotl genome using an approach that combined long-read sequencing, optical
      mapping and development of a new genome assembler (MARVEL). We observed a size
      expansion of introns and intergenic regions, largely attributable to
      multiplication of long terminal repeat retroelements. We provide evidence that
      intron size in developmental genes is under constraint and that species
      restricted genes may contribute to limb regeneration. The axolotl genome assembly
      does not contain the essential developmental gene Pax3. However, mutation of the
      axolotl Pax3 paralogue Pax7 resulted in an axolotl phenotype that was similar to
      those seen in Pax3-/- and Pax7-/- mutant mice. The axolotl genome provides a rich
      biological resource for developmental and evolutionary studies.

PMID- 29364873
TI  - Small-scale soft-bodied robot with multimodal locomotion.
AB  - Untethered small-scale (from several millimetres down to a few micrometres in all
      dimensions) robots that can non-invasively access confined, enclosed spaces may
      enable applications in microfactories such as the construction of tissue
      scaffolds by robotic assembly, in bioengineering such as single-cell manipulation
      and biosensing, and in healthcare such as targeted drug delivery and minimally
      invasive surgery. Existing small-scale robots, however, have very limited
      mobility because they are unable to negotiate obstacles and changes in texture or
      material in unstructured environments. Of these small-scale robots, soft robots
      have greater potential to realize high mobility via multimodal locomotion,
      because such machines have higher degrees of freedom than their rigid
      counterparts. Here we demonstrate magneto-elastic soft millimetre-scale robots
      that can swim inside and on the surface of liquids, climb liquid menisci, roll
      and walk on solid surfaces, jump over obstacles, and crawl within narrow tunnels.
      These robots can transit reversibly between different liquid and solid terrains,
      as well as switch between locomotive modes. They can additionally execute pick
      and-place and cargo-release tasks. We also present theoretical models to explain
      how the robots move. Like the large-scale robots that can be used to study
      locomotion, these soft small-scale robots could be used to study soft-bodied
      locomotion produced by small organisms.

PMID- 29364874
TI  - Biomechanics of predator-prey arms race in lion, zebra, cheetah and impala.
AB  - The fastest and most manoeuvrable terrestrial animals are found in savannah
      habitats, where predators chase and capture running prey. Hunt outcome and
      success rate are critical to survival, so both predator and prey should evolve to
      be faster and/or more manoeuvrable. Here we compare locomotor characteristics in
      two pursuit predator-prey pairs, lion-zebra and cheetah-impala, in their natural
      savannah habitat in Botswana. We show that although cheetahs and impalas were
      universally more athletic than lions and zebras in terms of speed, acceleration
      and turning, within each predator-prey pair, the predators had 20% higher muscle
      fibre power than prey, 37% greater acceleration and 72% greater deceleration
      capacity than their prey. We simulated hunt dynamics with these data and showed
      that hunts at lower speeds enable prey to use their maximum manoeuvring capacity
      and favour prey survival, and that the predator needs to be more athletic than
      its prey to sustain a viable success rate.

PMID- 29364876
TI  - A major lineage of non-tailed dsDNA viruses as unrecognized killers of marine
      bacteria.
AB  - The most abundant viruses on Earth are thought to be double-stranded DNA (dsDNA)
      viruses that infect bacteria. However, tailed bacterial dsDNA viruses
      (Caudovirales), which dominate sequence and culture collections, are not
      representative of the environmental diversity of viruses. In fact, non-tailed
      viruses often dominate ocean samples numerically, raising the fundamental
      question of the nature of these viruses. Here we characterize a group of marine
      dsDNA non-tailed viruses with short 10-kb genomes isolated during a study that
      quantified the diversity of viruses infecting Vibrionaceae bacteria. These
      viruses, which we propose to name the Autolykiviridae, represent a novel family
      within the ancient lineage of double jelly roll (DJR) capsid viruses.
      Ecologically, members of the Autolykiviridae have a broad host range, killing on
      average 34 hosts in four Vibrio species, in contrast to tailed viruses which kill
      on average only two hosts in one species. Biochemical and physical
      characterization of autolykiviruses reveals multiple virion features that cause
      systematic loss of DJR viruses in sequencing and culture-based studies, and we
      describe simple procedural adjustments to recover them. We identify DJR viruses
      in the genomes of diverse major bacterial and archaeal phyla, and in marine water
      column and sediment metagenomes, and find that their diversity greatly exceeds
      the diversity that is currently captured by the three recognized families of such
      viruses. Overall, these data suggest that viruses of the non-tailed dsDNA DJR
      lineage are important but often overlooked predators of bacteria and archaea that
      impose fundamentally different predation and gene transfer regimes on microbial
      systems than on tailed viruses, which form the basis of all environmental models
      of bacteria-virus interactions.

PMID- 29364875
TI  - Tissue-selective effects of nucleolar stress and rDNA damage in developmental
      disorders.
AB  - Many craniofacial disorders are caused by heterozygous mutations in general
      regulators of housekeeping cellular functions such as transcription or ribosome
      biogenesis. Although it is understood that many of these malformations are a
      consequence of defects in cranial neural crest cells, a cell type that gives rise
      to most of the facial structures during embryogenesis, the mechanism underlying
      cell-type selectivity of these defects remains largely unknown. By exploring
      molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both
      RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome
      biogenesis, we uncovered a previously unappreciated mechanism linking nucleolar
      dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we
      demonstrate that genetic perturbations associated with Treacher Collins syndrome,
      a craniofacial disorder caused by heterozygous mutations in components of the Pol
      I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to
      relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the
      chromatin targets, as well as inhibition of rRNA processing and downregulation of
      ribosomal protein gene transcription. These effects are cell-type-selective, cell
      autonomous, and involve activation of p53 tumour-suppressor protein. We further
      show that cranial neural crest cells are sensitized to p53-mediated apoptosis,
      but blocking DDX21 loss from the nucleolus and chromatin rescues both the
      susceptibility to apoptosis and the craniofacial phenotypes associated with
      Treacher Collins syndrome. This mechanism is not restricted to cranial neural
      crest cells, as blood formation is also hypersensitive to loss of DDX21
      functions. Accordingly, ribosomal gene perturbations associated with Diamond
      Blackfan anaemia disrupt DDX21 localization. At the molecular level, we
      demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that
      rDNA damage results in tissue-selective and dosage-dependent effects on
      craniofacial development. Taken together, our findings illustrate how disruption
      in general regulators that compromise nucleolar homeostasis can result in tissue
      selective malformations.

PMID- 29364877
TI  - Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation.
AB  - Varieties of RNA modification form the epitranscriptome for post-transcriptional
      regulation. 5-Methylcytosine (5-mC) is a sparse RNA modification in messenger RNA
      (mRNA) under physiological conditions. The function of RNA 5
      hydroxymethylcytosine (5-hmC) oxidized by ten-eleven translocation (Tet) proteins
      in Drosophila has been revealed more recently. However, the turnover and function
      of 5-mC in mammalian mRNA have been largely unknown. Tet2 suppresses myeloid
      malignancies mostly in an enzymatic activity-dependent manner, and is important
      in resolving inflammatory response in an enzymatic activity-independent way.
      Myelopoiesis is a common host immune response in acute and chronic infections;
      however, its epigenetic mechanism needs to be identified. Here we demonstrate
      that Tet2 promotes infection-induced myelopoiesis in an mRNA oxidation-dependent
      manner through Adar1-mediated repression of Socs3 expression at the post
      transcription level. Tet2 promotes both abdominal sepsis-induced emergency
      myelopoiesis and parasite-induced mast cell expansion through decreasing mRNA
      levels of Socs3, a key negative regulator of the JAK-STAT pathway that is
      critical for cytokine-induced myelopoiesis. Tet2 represses Socs3 expression
      through Adar1, which binds and destabilizes Socs3 mRNA in a RNA editing
      independent manner. For the underlying mechanism of Tet2 regulation at the mRNA
      level, Tet2 mediates oxidation of 5-mC in mRNA. Tet2 deficiency leads to the
      transcriptome-wide appearance of methylated cytosines, including ones in the 3'
      untranslated region of Socs3, which influences double-stranded RNA formation for
      Adar1 binding, probably through cytosine methylation-specific readers, such as
      RNA helicases. Our study reveals a previously unknown regulatory role of Tet2 at
      the epitranscriptomic level, promoting myelopoiesis during infection in the
      mammalian system by decreasing 5-mCs in mRNAs. Moreover, the inhibitory function
      of cytosine methylation on double-stranded RNA formation and Adar1 binding in
      mRNA reveals its new physiological role in the mammalian system.

PMID- 29364878
TI  - Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid
      metabolism.
AB  - The mammalian gut is colonized by numerous microorganisms collectively termed the
      microbiota, which have a mutually beneficial relationship with their host.
      Normally, the gut microbiota matures during ontogeny to a state of balanced
      commensalism marked by the absence of adverse inflammation. Subsets of innate
      lymphoid cells (ILCs) and conventional T cells are considered to have redundant
      functions in containment and clearance of microbial pathogens, but how these two
      major lymphoid-cell populations each contribute to shaping the mature commensal
      microbiome and help to maintain tissue homeostasis has not been determined. Here
      we identify, using advanced multiplex quantitative imaging methods, an extensive
      and persistent phosphorylated-STAT3 signature in group 3 ILCs and intestinal
      epithelial cells that is induced by interleukin (IL)-23 and IL-22 in mice that
      lack CD4+ T cells. By contrast, in immune-competent mice, phosphorylated-STAT3
      activation is induced only transiently by microbial colonization at weaning. This
      early signature is extinguished as CD4+ T cell immunity develops in response to
      the expanding commensal burden. Physiologically, the persistent IL-22 production
      from group 3 ILCs that occurs in the absence of adaptive CD4+ T-cell activity
      results in impaired host lipid metabolism by decreasing lipid transporter
      expression in the small bowel. These findings provide new insights into how
      innate and adaptive lymphocytes operate sequentially and in distinct ways during
      normal development to establish steady-state commensalism and tissue metabolic
      homeostasis.

PMID- 29364880
TI  - Strong disk winds traced throughout outbursts in black-hole X-ray binaries.
AB  - Recurring outbursts associated with matter flowing onto compact stellar remnants
      (such as black holes, neutron stars and white dwarfs) in close binary systems
      provide a way of constraining the poorly understood accretion process. The light
      curves of these outbursts are shaped by the efficiency of angular-momentum (and
      thus mass) transport in the accretion disks, which has traditionally been encoded
      in a viscosity parameter, alpha. Numerical simulations of the magneto-rotational
      instability that is believed to be the physical mechanism behind this transport
      yield values of alpha of roughly 0.1-0.2, consistent with values determined from
      observations of accreting white dwarfs. Equivalent viscosity parameters have
      hitherto not been estimated for disks around neutron stars or black holes. Here
      we report the results of an analysis of archival X-ray light curves of 21
      outbursts in black-hole X-ray binaries. By applying a Bayesian approach to a
      model of accretion, we determine corresponding values of alpha of around 0.2-1.0.
      These high values may be interpreted as an indication either of a very high
      intrinsic rate of angular-momentum transport in the disk, which could be
      sustained by the magneto-rotational instability only if a large-scale magnetic
      field threads the disk, or that mass is being lost from the disk through
      substantial outflows, which strongly shape the outburst in the black-hole X-ray
      binary. The lack of correlation between our estimates of alpha and the accretion
      state of the binaries implies that such outflows can remove a substantial
      fraction of the disk mass in all accretion states and therefore suggests that the
      outflows correspond to magnetically driven disk winds rather than thermally
      driven ones, which require specific radiative conditions.

PMID- 29364879
TI  - Mitochondrial translation requires folate-dependent tRNA methylation.
AB  - Folates enable the activation and transfer of one-carbon units for the
      biosynthesis of purines, thymidine and methionine. Antifolates are important
      immunosuppressive and anticancer agents. In proliferating lymphocytes and human
      cancers, mitochondrial folate enzymes are particularly strongly upregulated. This
      in part reflects the need for mitochondria to generate one-carbon units and
      export them to the cytosol for anabolic metabolism. The full range of uses of
      folate-bound one-carbon units in the mitochondrial compartment itself, however,
      has not been thoroughly explored. Here we show that loss of the catalytic
      activity of the mitochondrial folate enzyme serine hydroxymethyltransferase 2
      (SHMT2), but not of other folate enzymes, leads to defective oxidative
      phosphorylation in human cells due to impaired mitochondrial translation. We find
      that SHMT2, presumably by generating mitochondrial 5,10
      methylenetetrahydrofolate, provides methyl donors to produce the
      taurinomethyluridine base at the wobble position of select mitochondrial tRNAs.
      Mitochondrial ribosome profiling in SHMT2-knockout human cells reveals that the
      lack of this modified base causes defective translation, with preferential
      mitochondrial ribosome stalling at certain lysine (AAG) and leucine (UUG) codons.
      This results in the impaired expression of respiratory chain enzymes. Stalling at
      these specific codons also occurs in certain inborn errors of mitochondrial
      metabolism. Disruption of whole-cell folate metabolism, by either folate
      deficiency or antifolate treatment, also impairs the respiratory chain. In
      summary, mammalian mitochondria use folate-bound one-carbon units to methylate
      tRNA, and this modification is required for mitochondrial translation and thus
      oxidative phosphorylation.

PMID- 29364882
TI  - Quantitative and histological assessment of maternal-fetal transmission of
      Trypanosoma cruzi in guinea pigs: An experimental model of congenital Chagas
      disease.
AB  - OBJECTIVE: We evaluated the effect of Trypanosoma cruzi infection on fertility,
      gestation outcome, and maternal-fetal transmission in guinea pigs (Cavia
      porcellus). METHODS: Animals were infected with T. cruzi H4 strain (TcI lineage)
      before gestation (IBG) or during gestation (IDG). Tissue and sera samples of dams
      and fetuses were obtained near parturition. RESULTS: All IBG and IDG dams were
      seropositive by two tests, and exhibited blood parasite load of 1.62+/-2.2 and
      50.1+/-62 parasites/MUl, respectively, by quantitative PCR. Histological
      evaluation showed muscle fiber degeneration and cellular necrosis in all infected
      dams. Parasite nests were not detected in infected dams by histology. However,
      qPCR analysis detected parasites-eq/g heart tissue of 153+/-104.7 and 169.3+/
      129.4 in IBG and IDG dams, respectively. All fetuses of infected dams were
      positive for anti-parasite IgG antibodies and tissue parasites by qPCR, but
      presented a low level of tissue inflammatory infiltrate. Fetuses of IDG (vs. IBG)
      dams exhibited higher degree of muscle fiber degeneration and cellular necrosis
      in the heart and skeletal tissues. The placental tissue exhibited no inflammatory
      lesions and amastigote nests, yet parasites-eq/g of 381.2+/-34.3 and 79.2+/-84.9
      were detected in IDG and IBG placentas, respectively. Fetal development was
      compromised, and evidenced by a decline in weight, crow-rump length, and
      abdominal width in both groups. CONCLUSIONS: T. cruzi TcI has a high capacity of
      congenital transmission even when it was inoculated at a very low dose before or
      during gestation. Tissue lesions, parasite load, and fetal under development
      provide evidence for high virulence of the parasite during pregnancy. Despite
      finding of high parasite burden by qPCR, placentas were protected from cellular
      damage. Our studies offer an experimental model to study the efficacy of vaccines
      and drugs against congenital transmission of T. cruzi. These results also call
      for T. cruzi screening in pregnant women and adequate follow up of the newborns
      in endemic areas.

PMID- 29364883
TI  - Multifaceted functional implications of an endogenously expressed tRNA fragment
      in the vector mosquito Aedes aegypti.
AB  - The mosquito Aedes aegypti is the primary vector of human arboviral diseases
      caused by dengue, chikungunya and Zika viruses. Many studies have shown the
      potential roles of small RNA molecules such as microRNA, small interfering RNA
      and PIWI-interacting RNA in vector mosquitoes. The function of tRNA fragments
      (tRF), the newly discovered class of small RNAs, in mosquitoes is not known. In
      this study, we show that specific tRFs are expressed in significantly
      differential manner between males and females of Ae. aegypti strains. Specific
      tRFs also show differential response during developmental transition from larvae
      to adults, as well as after blood feeding of adult females. The expression
      pattern of tRFs upon blood feeding varied depending upon if the blood contained
      dengue virus, and also if the females were treated with antibiotic prior to
      feeding to cleanse of the gut bacteria. Our findings show that a single tRF
      derived from the precursor sequences of a tRNA-Gly was differentially expressed
      between males and females, developmental transitions and also upon blood feeding
      by females of two laboratory strains that vary in midgut susceptibility to dengue
      virus infection. The multifaceted functional implications of this specific tRF
      suggest that biogenesis of small regulatory molecules from a tRNA can have wide
      ranging effects on key aspects of Ae. aegypti vector biology.

PMID- 29364884
TI  - The cost-effectiveness of alternative vaccination strategies for polyvalent
      meningococcal vaccines in Burkina Faso: A transmission dynamic modeling study.
AB  - BACKGROUND: The introduction of a conjugate vaccine for serogroup A Neisseria
      meningitidis has dramatically reduced disease in the African meningitis belt. In
      this context, important questions remain about the performance of different
      vaccine policies that target remaining serogroups. Here, we estimate the health
      impact and cost associated with several alternative vaccination policies in
      Burkina Faso. METHODS AND FINDINGS: We developed and calibrated a mathematical
      model of meningococcal transmission to project the disability-adjusted life years
      (DALYs) averted and costs associated with the current Base policy (serogroup A
      conjugate vaccination at 9 months, as part of the Expanded Program on
      Immunization [EPI], plus district-specific reactive vaccination campaigns using
      polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks)
      and three alternative policies: (1) Base Prime: novel polyvalent meningococcal
      conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also
      used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide
      catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except
      the nationwide campaign includes individuals up to 29 years old. Over a 30-year
      simulation period, Prevention 2 would avert 78% of the meningococcal cases (95%
      prediction interval: 63%-90%) expected under the Base policy if serogroup A is
      not replaced by remaining serogroups after elimination, and would avert 87% (77%
      93%) of meningococcal cases if complete strain replacement occurs. Compared to
      the Base policy and at the PMC vaccine price of US$4 per dose, strategies that
      use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be
      cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490),
      US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted,
      respectively, if strain replacement does not occur. An important potential
      limitation of our study is the simplifying assumption that all circulating
      meningococcal serogroups can be aggregated into a single group; while this
      assumption is critical for model tractability, it would compromise the insights
      derived from our model if the effectiveness of the vaccine differs markedly
      between serogroups or if there are complex between-serogroup interactions that
      influence the frequency and magnitude of future meningitis epidemics.
      CONCLUSIONS: Our results suggest that a vaccination strategy that includes a
      catch-up nationwide immunization campaign in young adults with a PMC vaccine and
      the addition of this new vaccine into EPI is cost-effective and would avert a
      substantial portion of meningococcal cases expected under the current World
      Health Organization-recommended strategy of reactive vaccination. This analysis
      is limited to Burkina Faso and assumes that polyvalent vaccines offer equal
      protection against all meningococcal serogroups; further studies are needed to
      evaluate the robustness of this assumption and applicability for other countries
      in the meningitis belt.

PMID- 29364885
TI  - Does a narcissism epidemic exist in modern western societies? Comparing
      narcissism and self-esteem in East and West Germany.
AB  - Narcissism scores are higher in individualistic cultures compared with more
      collectivistic cultures. However, the impact of sociocultural factors on
      narcissism and self-esteem has not been well described. Germany was formerly
      divided into two different social systems, each with distinct economic, political
      and national cultures, and was reunified in 1989/90. Between 1949 and 1989/90,
      West Germany had an individualistic culture, whereas East Germany had a more
      collectivistic culture. The German reunification provides an exceptional
      opportunity to investigate the impact of sociocultural and generational
      differences on narcissism and self-esteem. In this study, we used an anonymous
      online survey to assess grandiose narcissism with the Narcissistic Personality
      Inventory (NPI) and the Pathological Narcissism Inventory (PNI) to assess
      grandiose and vulnerable aspects of narcissism, and self-esteem with the
      Rosenberg Self-Esteem Scale (RSE) in 1,025 German individuals. Data were analyzed
      according to age and place of birth. Our results showed that grandiose narcissism
      was higher and self-esteem was lower in individuals who grew up in former West
      Germany compared with former East Germany. Further analyses indicated no
      significant differences in grandiose narcissism, vulnerable narcissism or self
      esteem in individuals that entered school after the German reunification (<= 5
      years of age in 1989). In the middle age cohort (6-18 years of age in 1989),
      significant differences in vulnerable narcissism, grandiose narcissism and self
      esteem were observed. In the oldest age cohort (> 19 years of age in 1989),
      significant differences were only found in one of the two scales assessing
      grandiose narcissism (NPI). Our data provides empirical evidence that
      sociocultural factors are associated with differences in narcissism and self
      esteem.

PMID- 29364886
TI  - Safety and pharmacokinetics of the Fc-modified HIV-1 human monoclonal antibody
      VRC01LS: A Phase 1 open-label clinical trial in healthy adults.
AB  - BACKGROUND: VRC01 is a human broadly neutralizing monoclonal antibody (bnMAb)
      against the CD4-binding site of the HIV-1 envelope glycoprotein (Env) that is
      currently being evaluated in a Phase IIb adult HIV-1 prevention efficacy trial.
      VRC01LS is a modified version of VRC01, designed for extended serum half-life by
      increased binding affinity to the neonatal Fc receptor. METHODS AND FINDINGS:
      This Phase I dose-escalation study of VRC01LS in HIV-negative healthy adults was
      conducted by the Vaccine Research Center (VRC) at the National Institutes of
      Health (NIH) Clinical Center (Bethesda, MD). The age range of the study
      volunteers was 21-50 years; 51% of study volunteers were male and 49% were
      female. Primary objectives were safety and tolerability of VRC01LS intravenous
      (IV) infusions at 5, 20, and 40 mg/kg infused once, 20 mg/kg given three times at
      12-week intervals, and subcutaneous (SC) delivery at 5 mg/kg delivered once, or
      three times at 12-week intervals. Secondary objectives were pharmacokinetics
      (PK), serum neutralization activity, and development of antidrug antibodies.
      Enrollment began on November 16, 2015, and concluded on August 23, 2017. This
      report describes the safety data for the first 37 volunteers who received
      administrations of VRC01LS. There were no serious adverse events (SAEs) or dose
      limiting toxicities. Mild malaise and myalgia were the most common adverse events
      (AEs). There were six AEs assessed as possibly related to VRC01LS administration,
      and all were mild in severity and resolved during the study. PK data were modeled
      based on the first dose of VRC01LS in the first 25 volunteers to complete their
      schedule of evaluations. The mean (+/-SD) serum concentration 12 weeks after one
      IV administration of 20 mg/kg or 40 mg/kg were 180 +/- 43 MUg/mL (n = 7) and 326
      +/- 35 MUg/mL (n = 5), respectively. The mean (+/-SD) serum concentration 12
      weeks after one IV and SC administration of 5 mg/kg were 40 +/- 3 MUg/mL (n = 2)
      and 25 +/- 5 MUg/mL (n = 9), respectively. Over the 5-40 mg/kg IV dose range (n =
      16), the clearance was 36 +/- 8 mL/d with an elimination half-life of 71 +/- 18
      days. VRC01LS retained its expected neutralizing activity in serum, and anti
      VRC01 antibody responses were not detected. Potential limitations of this study
      include the small sample size typical of Phase I trials and the need to further
      describe the PK properties of VRC01LS administered on multiple occasions.
      CONCLUSIONS: The human bnMAb VRC01LS was safe and well tolerated when delivered
      intravenously or subcutaneously. The half-life was more than 4-fold greater when
      compared to wild-type VRC01 historical data. The reduced clearance and extended
      half-life may make it possible to achieve therapeutic levels with less frequent
      and lower-dose administrations. This would potentially lower the costs of
      manufacturing and improve the practicality of using passively administered
      monoclonal antibodies (mAbs) for the prevention of HIV-1 infection. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT02599896.

PMID- 29364888
TI  - Predicting peak spectral sensitivities of vertebrate cone visual pigments using
      atomistic molecular simulations.
AB  - Vision is the dominant sensory modality in many organisms for foraging, predator
      avoidance, and social behaviors including mate selection. Vertebrate visual
      perception is initiated when light strikes rod and cone photoreceptors within the
      neural retina of the eye. Sensitivity to individual colors, i.e., peak spectral
      sensitivities (lambdamax) of visual pigments, are a function of the type of
      chromophore and the amino acid sequence of the associated opsin protein in the
      photoreceptors. Large differences in peak spectral sensitivities can result from
      minor differences in amino acid sequence of cone opsins. To determine how minor
      sequence differences could result in large spectral shifts we selected a
      spectrally-diverse group of 14 teleost Rh2 cone opsins for which sequences and
      lambdamax are experimentally known. Classical molecular dynamics simulations were
      carried out after embedding chromophore-associated homology structures within
      explicit bilayers and water. These simulations revealed structural features of
      visual pigments, particularly within the chromophore, that contributed to
      diverged spectral sensitivities. Statistical tests performed on all the observed
      structural parameters associated with the chromophore revealed that a two-term,
      first-order regression model was sufficient to accurately predict lambdamax over
      a range of 452-528 nm. The approach was accurate, efficient and simple in that
      site-by-site molecular modifications or complex quantum mechanics models were not
      required to predict lambdamax. These studies identify structural features
      associated with the chromophore that may explain diverged spectral sensitivities,
      and provide a platform for future, functionally predictive opsin modeling.

PMID- 29364887
TI  - Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar
      neuronal pathways and functions.
AB  - Dystonia is characterized by involuntary muscle contractions. Its many forms are
      genetically, phenotypically and etiologically diverse and it is unknown whether
      their pathogenesis converges on shared pathways. Mutations in THAP1 [THAP
      (Thanatos-associated protein) domain containing, apoptosis associated protein 1],
      a ubiquitously expressed transcription factor with DNA binding and protein
      interaction domains, cause dystonia, DYT6. There is a unique, neuronal 50-kDa
      Thap1-like immunoreactive species, and Thap1 levels are auto-regulated on the
      mRNA level. However, THAP1 downstream targets in neurons, and the mechanism via
      which it causes dystonia are largely unknown. We used RNA-Seq to assay the in
      vivo effect of a heterozygote Thap1 C54Y or DeltaExon2 allele on the gene
      transcription signatures in neonatal mouse striatum and cerebellum. Enriched
      pathways and gene ontology terms include eIF2alpha Signaling, Mitochondrial
      Dysfunction, Neuron Projection Development, Axonal Guidance Signaling, and
      Synaptic LongTerm Depression, which are dysregulated in a genotype and tissue
      dependent manner. Electrophysiological and neurite outgrowth assays were
      consistent with those enrichments, and the plasticity defects were partially
      corrected by salubrinal. Notably, several of these pathways were recently
      implicated in other forms of inherited dystonia, including DYT1. We conclude that
      dysfunction of these pathways may represent a point of convergence in the
      pathophysiology of several forms of inherited dystonia.

PMID- 29364889
TI  - Serum metabolome changes in adult patients with severe dengue in the critical and
      recovery phases of dengue infection.
AB  - Dengue virus (DENV) is the most prevalent arbovirus leading to an estimated 100
      million symptomatic dengue infections every year. DENV can cause a spectrum of
      clinical manifestations, ranging from mild dengue fever (DF) to more life
      threatening forms such as dengue hemorrhagic fever (DHF). The clinical symptoms
      of DHF become evident typically at the critical phase of infection (5-7 days
      after onset of fever), yet the mechanisms that trigger transition from DF to DHF
      are not well understood. We performed a mass spectrometry-based metabolomic
      profiling of sera from adult DF and DHF patients at the critical and recovery
      phases of infection. There were 29 differentially expressed metabolites
      identified between DF and DHF at the critical phase. These include bile acids,
      purines, acylcarnitines, phospholipids, and amino acids. Bile acids were observed
      up to 5 fold higher levels among DHF compared to DF patients and were
      significantly correlated to the higher levels of aspartate transaminase (AST) and
      alanine transaminase (ALT), suggestive of liver injury among DHF. Uric acid, the
      most abundant antioxidant in the blood, was observed to be 1.5 fold lower among
      DHF compared to DF patients. This could result in decreased capacity of
      endogenous antioxidant defense and elevated oxidative stress among DHF patients.
      In the recovery phase, the levels of eight metabolites were still significantly
      higher or lower among DHF patients, including chenodeoxyglycocholic acid, one of
      the bile acids observed at the critical phase. This indicates potential prolonged
      adverse impact on the liver due to DENV infection in DHF patients. Our study
      identified altered metabolic pathways linked to DHF in the critical and recovery
      phases of dengue infection and provided insights into the different host and DENV
      interactions between DF and DHF. The results advance our understanding on the
      mechanisms of DHF pathogenesis, alluding to possible novel therapeutic targets to
      dengue management.

PMID- 29364890
TI  - 5-aminolevulinic acid (ALA) deficiency causes impaired glucose tolerance and
      insulin resistance coincident with an attenuation of mitochondrial function in
      aged mice.
AB  - In vertebrates, the initial step in heme biosynthesis is the production of 5
      aminolevulinic acid (ALA) by ALA synthase (ALAS). ALA formation is believed to be
      the rate-limiting step for cellular heme production. Recently, several cohort
      studies have demonstrated the potential of ALA as a treatment for individuals
      with prediabetes and type-2 diabetes mellitus. These studies imply that a
      mechanism exists by which ALA or heme can control glucose metabolism. The ALAS1
      gene encodes a ubiquitously expressed isozyme. Mice heterozygous null for ALAS1
      (A1+/-s) experience impaired glucose tolerance (IGT) and insulin resistance (IR)
      beyond 20-weeks of age (aged A1+/-s). IGT and IR were remedied in aged A1+/-s by
      the oral administration of ALA for 1 week. However, the positive effect of ALA
      proved to be reversible and was lost upon termination of ALA administration. In
      the skeletal muscle of aged A1+/-s an attenuation of mitochondrial function is
      observed, coinciding with IGT and IR. Oral administration of ALA for 1-week
      brought about only a partial improvement in mitochondrial activity however, a 6
      week period of ALA treatment was sufficient to remedy mitochondrial function.
      Studies on differentiated C2C12 myocytes indicate that the impairment of glucose
      metabolism is a cell autonomous effect and that ALA deficiency ultimately leads
      to heme depletion. This sequela is evidenced by a reduction of glucose uptake in
      C2C12 cells following the knockdown of ALAS1 or the inhibition of heme
      biosynthesis by succinylacetone. Our data provide in vivo proof that ALA
      deficiency attenuates mitochondrial function, and causes IGT and IR in an age
      dependent manner. The data reveals an unexpected metabolic link between heme and
      glucose that is relevant to the pathogenesis of IGT/IR.

PMID- 29364891
TI  - Move faster, think later: Women who play action video games have quicker visually
      guided responses with later onset visuomotor-related brain activity.
AB  - A history of action video game (AVG) playing is associated with improvements in
      several visuospatial and attention-related skills and these improvements may be
      transferable to unrelated tasks. These facts make video games a potential medium
      for skill-training and rehabilitation. However, examinations of the neural
      correlates underlying these observations are almost non-existent in the
      visuomotor system. Further, the vast majority of studies on the effects of a
      history of AVG play have been done using almost exclusively male participants.
      Therefore, to begin to fill these gaps in the literature, we present findings
      from two experiments. In the first, we use functional MRI to examine brain
      activity in experienced, female AVG players during visually-guided reaching. In
      the second, we examine the kinematics of visually-guided reaching in this
      population. Imaging data demonstrate that relative to women who do not play, AVG
      players have less motor-related preparatory activity in the cuneus, middle
      occipital gyrus, and cerebellum. This decrease is correlated with estimates of
      time spent playing. Further, these correlations are strongest during the
      performance of a visuomotor mapping that spatially dissociates eye and arm
      movements. However, further examinations of the full time-course of visuomotor
      related activity in the AVG players revealed that the decreased activity during
      motor preparation likely results from a later onset of activity in AVG players,
      which occurs closer to beginning motor execution relative to the non-playing
      group. Further, the data presented here suggest that this later onset of
      preparatory activity represents greater neural efficiency that is associated with
      faster visually-guided responses.

PMID- 29364892
TI  - Presence of B. thailandensis and B. thailandensis expressing B. pseudomallei-like
      capsular polysaccharide in Thailand, and their associations with serological
      response to B. pseudomallei.
AB  - BACKGROUND: Burkholderia pseudomallei is an environmental Gram-negative bacillus
      and the cause of melioidosis. B. thailandensis, some strains of which express a
      B. pseudomallei-like capsular polysaccharide (BTCV), is also commonly found in
      the environment in Southeast Asia but is considered non-pathogenic. The aim of
      the study was to determine the distribution of B. thailandensis and its capsular
      variant in Thailand and investigate whether its presence is associated with a
      serological response to B. pseudomallei. METHODOLOGY/PRINCIPAL FINDINGS: We
      evaluated the presence of B. pseudomallei and B. thailandensis in 61 rice fields
      in Northeast (n = 21), East (n = 19) and Central (n = 21) Thailand. We found BTCV
      in rice fields in East and Central but not Northeast Thailand. Fourteen fields
      were culture positive for B. pseudomallei alone, 8 for B. thailandensis alone, 11
      for both B. pseudomallei and B. thailandensis, 6 for both B. thailandensis and
      BTCV, and 5 for B. pseudomallei, B. thailandensis and BTCV. Serological testing
      using the indirect hemagglutination assay (IHA) of 96 farmers who worked in the
      study fields demonstrated that farmers who worked in B. pseudomallei-positive
      fields had higher IHA titers than those who worked in B. pseudomallei-negative
      fields (median 1:40 [range: <1:10-1:640] vs. <1:10 [range: <1:10-1:320], p =
      0.002). In a multivariable ordered logistic regression model, IHA titers were
      significantly associated with the presence of B. pseudomallei (aOR = 3.7; 95% CI
      1.8-7.8, p = 0.001) but were not associated with presence of B. thailandensis (p
      = 0.32) or BTCV (p = 0.32). One sequence type (696) was identified for the 27
      BTCV isolates tested. CONCLUSIONS/SIGNIFICANCE: This is the first report of BTCV
      in Thailand. The presence of B. pseudomallei and B. thailandensis in the same
      field was not uncommon. Our findings suggest that IHA positivity of healthy rice
      farmers in Thailand is associated with the presence of B. pseudomallei in rice
      fields rather than B. thailandensis or BTCV.

PMID- 29364893
TI  - Sequence determinants of protein phase behavior from a coarse-grained model.
AB  - Membraneless organelles important to intracellular compartmentalization have
      recently been shown to comprise assemblies of proteins which undergo liquid
      liquid phase separation (LLPS). However, many proteins involved in this phase
      separation are at least partially disordered. The molecular mechanism and the
      sequence determinants of this process are challenging to determine experimentally
      owing to the disordered nature of the assemblies, motivating the use of
      theoretical and simulation methods. This work advances a computational framework
      for conducting simulations of LLPS with residue-level detail, and allows for the
      determination of phase diagrams and coexistence densities of proteins in the two
      phases. The model includes a short-range contact potential as well as a
      simplified treatment of electrostatic energy. Interaction parameters are
      optimized against experimentally determined radius of gyration data for multiple
      unfolded or intrinsically disordered proteins (IDPs). These models are applied to
      two systems which undergo LLPS: the low complexity domain of the RNA-binding
      protein FUS and the DEAD-box helicase protein LAF-1. We develop a novel
      simulation method to determine thermodynamic phase diagrams as a function of the
      total protein concentration and temperature. We show that the model is capable of
      capturing qualitative changes in the phase diagram due to phosphomimetic
      mutations of FUS and to the presence or absence of the large folded domain in LAF
      1. We also explore the effects of chain-length, or multivalency, on the phase
      diagram, and obtain results consistent with Flory-Huggins theory for polymers.
      Most importantly, the methodology presented here is flexible so that it can be
      easily extended to other pair potentials, be used with other enhanced sampling
      methods, and may incorporate additional features for biological systems of
      interest.

PMID- 29364894
TI  - Serum calcification propensity is independently associated with disease activity
      in systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is associated with severe
      cardiovascular complications. The T50 score is a novel functional blood test
      quantifying calcification propensity in serum. High calcification propensity (or
      low T50) is a strong and independent determinant of all-cause mortality in
      various patient populations. METHODS: A total of 168 patients with >= 4 American
      College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus
      erythematosus Cohort Study (SSCS) were included in this analysis. Serum
      calcification propensity was assessed using time-resolved nephelometry. RESULTS:
      The cohort mainly consisted of female (85%), middle-aged (43+/-14 years)
      Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum
      creatinine and serum protein levels explaining 43% of the variation at baseline.
      Integrating disease activity (SELENA-SLEDAI) into this multivariate model
      revealed a significant association between disease activity and T50 levels. In a
      subgroup analysis considering only patients with active disease (SELENA-SLEDAI
      score >=4) we found a negative association between T50 and SELENA-SLEDAI score at
      baseline (Spearman's rho -0.233, P = 0.02). CONCLUSIONS: Disease activity and T50
      are closely associated. Moreover, T50 levels identify a subgroup of SLE patients
      with ongoing systemic inflammation as mirrored by increased disease activity. T50
      could be a promising biomarker reflecting SLE disease activity and might offer an
      earlier detection tool for high-risk patients.

PMID- 29364895
TI  - Difficult decisions: Evaluating individual and couple-level fertility intentions
      and HIV acquisition among HIV serodiscordant couples in Zambia.
AB  - INTRODUCTION: Attempts to conceive and pregnancy may increase HIV transmission to
      sex partners and infants. Our study evaluated the association between fertility
      intentions and HIV acquisition among Zambian HIV-serodiscordant couples. METHODS:
      We collected demographic, behavioral, clinical exposures, and data on fertility
      intentions in a cohort of HIV-serodiscordant couples in Lusaka, Zambia from 2005
      to 2012. We evaluated factors associated with fertility intentions stratified by
      gender using multivariable logistic regression. Multivariable Cox proportional
      hazard models were used to evaluate the associations between fertility intentions
      and HIV acquisition controlling for a priori confounders and covariates that
      substantially (>10%) changed the effect estimates in univariate analyses.
      RESULTS: Among 1,029 serodiscordant couples, 311 agreed that they wanted children
      in the future (30%), 368 agreed they did not want children (36%), and 344 couples
      disagreed about having children (34%), with men more likely than women to want
      children. Women wanting child(ren) was associated with increased odds of baseline
      pregnancy (adjusted odds ratio [aOR] = 4.80 (95% confidence interval [CI] = 2.93,
      7.85)), fewer previous pregnancies (aOR = 0.85 per additional pregnancy (95% CI =
      0.78, 0.93)), and partner fertility intention (aOR = 2.89 (95% CI = 2.14, 3.91))
      adjusting for woman's age, literacy, years cohabiting and HIV status. Men wanting
      child(ren) was associated with younger age (aOR = 0.96 per year (95% CI = 0.93,
      0.99)), fewer years cohabiting (aOR = 0.95 (95% CI = 0.92, 0.98)), number of
      previous partners' pregnancies (aOR = 0.90 (95% CI = 0.82, 0.98)), and partner
      fertility intention (aOR = 3.00 (95% CI = 2.21, 4.07)) adjusting for partner's
      age, literacy, HIV status and partner's baseline pregnancy. In adjusted survival
      analyses, HIV-negative women were more likely to seroconvert if they themselves
      wanted children (aHR = 2.36 (95% CI = 1.41, 3.96)) vs. did not want children, or
      if their partner wanted children (aHR = 2.34 (95% CI = 1.33, 4.11)) vs. did not
      want children, or if the couple agreed that they wanted children (aHR = 2.08 (95%
      CI = 1.01, 4.30)), adjusting for women's age, women's literacy, previous
      pregnancies and time in study. HIV-negative men were more likely to seroconvert
      if their female partner wanted a child in the next 12-months (aHR = 1.94 (95% CI
      = 1.02, 3.68)) vs. did not want children, and when both partners wanted children
      (aHR = 2.02 (CI = 1.09, 3.73)) vs. they did not want children, adjusting for
      men's age and literacy, couple income, number of live children, male circumcision
      status and time in study. CONCLUSION: Women had increased risk of HIV acquisition
      if they and/or their partner wanted a child, while men had increased risk of HIV
      acquisition when their partner or if both partners agreed that they wanted
      children. Safer-conception interventions are needed to protect HIV uninfected
      women and men from HIV acquisition in HIV-serodiscordant couples who want
      children.

PMID- 29364896
TI  - Ac-SDKP decreases mortality and cardiac rupture after acute myocardial
      infarction.
AB  - The natural peptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) decreases
      inflammation in chronic diseases such as hypertension and heart failure. However,
      Ac-SDKP effects on acute inflammatory responses during myocardial infarction (MI)
      are unknown. During the first 72 hours post-MI, neutrophils, M1 macrophages (pro
      inflammatory), and M2 macrophages (pro-resolution) and release of myeloperoxidase
      (MPO) and matrix metalloproteinases (MMP) are involved in cardiac rupture. We
      hypothesized that in the acute stage of MI, Ac-SDKP decreases the incidence of
      cardiac rupture and mortality by preventing immune cell infiltration as well as
      by decreasing MPO and MMP expression. MI was induced by ligating the left
      descending coronary artery in C57BL/6 mice. Vehicle or Ac-SDKP (1.6 mg/kg/d) was
      infused via osmotic minipump. Cardiac immune cell infiltration was assessed by
      flow cytometry, cardiac MPO and MMP levels were measured at 24-48 hrs post-MI.
      Cardiac rupture and mortality incidence were determined at 7 days post-MI. In
      infarcted mice, Ac-SDKP significantly decreased cardiac rupture incidence from
      51.0% (26 of 51 animals) to 27.3% (12 of 44) and mortality from 56.9% (29 of 51)
      to 31.8% (14 of 44). Ac-SDKP reduced M1 macrophages in cardiac tissue after MI,
      without affecting M2 macrophages and neutrophils. Ac-SDKP decreased MMP-9
      activation in infarcted hearts with no changes on MPO expression. Ac-SDKP
      prevents cardiac rupture and decreases mortality post-acute MI. These protective
      effects of Ac-SDKP are associated with decreased pro-inflammatory M1 macrophage
      infiltration and MMP-9 activation.

PMID- 29364897
TI  - Slower saccadic reading in Parkinson's disease.
AB  - Idiopathic Parkinson's Disease (PD) is characterized by degeneration of
      dopaminergic and other neurons, leading to motor and non-motor deficits. Abnormal
      eye movements in PD, including fixations, saccades, and convergence, are well
      described. However, saccadic reading, which requires serial and alternating
      saccades and fixations, is not well studied, despite its obvious impact on the
      quality of life. In this study, we assessed saccadic reading using variations of
      the King-Devick (KD) test, a rapid single digit number naming test, as a way to
      assess the ability to make serial left-to-right ocular motor movements necessary
      for reading. We recruited 42 treated PD patients and 80 age-matched controls and
      compared their reading times with a variety of measures, including age, duration
      of disease, Unified Parkinson's Disease Rating Scale (UPDRS), the National Eye
      Institute 25-Item Visual Functioning Questionnaire 25 (VFQ-25), and Montreal
      Cognitive assessment (MoCA) test. The subjects performed 4 trials of reading 120
      single digit numbers aloud as fast as possible without making errors. In each
      trial, they read 3 pages (KD1, KD2, and KD3), and each page contained 40 numbers
      per page in 8 lines with 5 numbers/line. We found that PD patients read about 20%
      slower than controls on all tests (KD1, 2, and 3 tests) (p < 0.02), and both
      groups read irregularly spaced numbers slower than regularly spaced numbers.
      Having lines between numbers to guide reading (KD1 tests) did not impact reading
      time in both PD and controls, but increased visual crowding as a result of
      decreased spacing between numbers (KD3 tests) was associated with significantly
      slower reading times in both PD and control groups. Our study revealed that
      saccadic reading is slower in PD, but controls and PD patients are both impacted
      by visuospatial planning challenges posed by increased visual crowding and
      irregularity of number spacing. Reading time did not correlate with UPDRS or MoCA
      scores in PD patients but significantly correlated with age, duration of disease,
      and VFQ-25 scores. The presence of convergence insufficiency did not
      significantly correlate with reading time in PD patients, although on average
      there was slower reading time in those with convergence insufficiency by 8 s (p =
      0.2613). We propose that a simple reading task using 120 single-digit numbers can
      be used as a screening tool in the clinical setting to assess functional ocular
      motor difficulties in Parkinson's disease that can have a profound impact on
      quality of life.

PMID- 29364898
TI  - Vocal complexity and sociality in spotted paca (Cuniculus paca).
AB  - The evolution of sociality is related to many ecological factors that act on
      animals as selective forces, thus driving the formation of groups. Group size
      will depend on the payoffs of group living. The Social Complexity Hypothesis for
      Communication (SCHC) predicts that increases in group size will be related to
      increases in the complexity of the communication among individuals. This
      hypothesis, which was confirmed in some mammal societies, may be useful to trace
      sociality in the spotted paca (Cuniculus paca), a Neotropical caviomorph rodent
      reported as solitary. There are, however, sightings of groups in the wild, and
      farmers easily form groups of spotted paca in captivity. Thus, we aimed to
      describe the acoustic repertoire of captive spotted paca to test the SCHC and to
      obtain insights about the sociability of this species. Moreover, we aimed to
      verify the relationship between group size and acoustic repertoire size of
      caviomorph rodents, to better understand the evolution of sociality in this
      taxon. We predicted that spotted paca should display a complex acoustic
      repertoire, given their social behavior in captivity and group sightings in the
      wild. We also predicted that in caviomorph species the group size would increase
      with acoustic repertoire, supporting the SCHC. We performed a Linear Discriminant
      Analysis (LDA) based on acoustic parameters of the vocalizations recorded. In
      addition, we applied an independent contrasts approach to investigate sociality
      in spotted paca following the social complexity hypothesis, independent of
      phylogeny. Our analysis showed that the spotted paca's acoustic repertoire
      contains seven vocal types and one mechanical signal. The broad acoustic
      repertoire of the spotted paca might have evolved given the species' ability to
      live in groups. The relationship between group size and the size of the acoustic
      repertoires of caviomorph species was confirmed, providing additional support for
      the SCHC in yet another group of diverse mammals-caviomorph rodents.

PMID- 29364899
TI  - Contextual correlates of happiness in European adults.
AB  - OBJECTIVES: We aimed to examine the associations of both objectively assessed and
      perceived physical and social neighborhood characteristics with happiness in
      European adults. In addition, we aimed to study how these associations differed
      among subgroups. METHODS: Participants (N = 6037) of the cross-sectional
      SPOTLIGHT survey reported on their level of happiness using a 5-point Likert
      scale, and on perceived physical and social environmental neighborhood
      characteristics. Objective physical environmental characteristics were assessed
      using a Google Street View-based neighborhood audit. Associations of 14 physical
      and social environmental characteristics with happiness were analyzed using
      multivariable multinomial regression analyses with clustered standard errors.
      RESULTS: Living in neighborhoods with higher levels of aesthetics and more water
      and green space was associated with being very happy. Individuals who perceived
      their neighborhood to be safer, more functional and more aesthetic were more
      likely to be very happy. The associations of functionality and aesthetics with
      happiness were strongest in the Ghent region (Belgium), the Randstad (the
      Netherlands) and Greater London (United Kingdom). Perceived absence of air
      pollution was only associated with higher levels of happiness in more highly
      educated participants. Individuals with a larger social network, more social
      cohesion and who trusted their neighbors were more likely to be very happy. The
      association between social networks and happiness was somewhat stronger in men
      than in women. In general, the associations between environmental characteristics
      and happiness had similar directions and sizes across socio-economic and socio
      demographic subgroups. CONCLUSIONS: This European study provided evidence that
      both objectively assessed and perceived physical and social characteristics of
      the neighborhood environment are associated with the happiness of its residents.

PMID- 29364900
TI  - De Novo characterization of transcriptomes from two North American Papaipema stem
      borers (Lepidoptera: Noctuidae).
AB  - Stem-borers in the genus Papaipema (Lepidoptera: Noctuidae) range from highly
      polyphagous agricultural pests to specialists on more than 20 families of
      flowering plants, many of them highly toxic. Papaipema is the largest genus of
      noctuids endemic to North America and provides an excellent study system for the
      evolution of noctuid host plant use. To improve the availability of genomic
      resources for such investigations, we performed de novo transcriptome sequencing
      and assembly for two specialist Papaipema with unusual larval hosts: P.
      speciosissima, which is associated with ferns, and the undescribed P. "sp. 4,"
      which is associated with bamboo. The resulting transcriptomes were similar in
      terms of completeness, gene count, and gene identity, but we identified some
      8,000 genes (~17% of each transcriptome) not shared between the two species.
      While some of these have identifiable orthologs in other Lepidoptera, ~5% of each
      transcriptome consists of species-specific genes. We examine the function of
      these genes and find that almost half have retrotransposon-related functional
      domains. The potential role of species-specific genes is discussed, and the
      expansion of certain retrotransposon families in Papaipema is examined.

PMID- 29364901
TI  - Testing spatial heterogeneity with stock assessment models.
AB  - This paper describes a methodology that combines meta-population theory and stock
      assessment models to gain insights about spatial heterogeneity of the meta
      population in an operational time frame. The methodology was tested with
      stochastic simulations for different degrees of connectivity between sub
      populations and applied to two case studies, North Sea cod (Gadus morua) and
      Northeast Atlantic sardine (Sardina pilchardus). Considering that the biological
      components of a population can be partitioned into discrete spatial units, we
      extended this idea into a property of additivity of sub-population abundances. If
      the additivity results hold true for putative sub-populations, then assessment
      results based on sub-populations will provide information to develop and monitor
      the implementation of finer scale/local management. The simulation study
      confirmed that when sub-populations are independent and not too heterogeneous
      with regards to productivity, the sum of stock assessment model estimates of sub
      populations' SSB is similar to the SSB estimates of the meta-population. It also
      showed that a strong diffusion process can be detected and that the stronger the
      connection between SSB and recruitment, the better the diffusion process will be
      detected. On the other hand it showed that weak to moderate diffusion processes
      are not easy to identify and large differences between sub-populations
      productivities may be confounded with weak diffusion processes. The application
      to North Sea cod and Atlantic sardine exemplified how much insight can be gained.
      In both cases the results obtained were sufficiently robust to support the
      regional analysis.

PMID- 29364902
TI  - Marine biodiversity at the end of the world: Cape Horn and Diego Ramirez islands.
AB  - The vast and complex coast of the Magellan Region of extreme southern Chile
      possesses a diversity of habitats including fjords, deep channels, and extensive
      kelp forests, with a unique mix of temperate and sub-Antarctic species. The Cape
      Horn and Diego Ramirez archipelagos are the most southerly locations in the
      Americas, with the southernmost kelp forests, and some of the least explored
      places on earth. The giant kelp Macrocystis pyrifera plays a key role in
      structuring the ecological communities of the entire region, with the large brown
      seaweed Lessonia spp. forming dense understories. Kelp densities were highest
      around Cape Horn, followed by Diego Ramirez, and lowest within the fjord region
      of Francisco Coloane Marine Park (mean canopy densities of 2.51 kg m-2, 2.29 kg m
      2, and 2.14 kg m-2, respectively). There were clear differences in marine
      communities among these sub-regions, with the lowest diversity in the fjords. We
      observed 18 species of nearshore fishes, with average species richness nearly 50%
      higher at Diego Ramirez compared with Cape Horn and Francisco Coloane. The number
      of individual fishes was nearly 10 times higher at Diego Ramirez and 4 times
      higher at Cape Horn compared with the fjords. Dropcam surveys of mesophotic
      depths (53-105 m) identified 30 taxa from 25 families, 15 classes, and 7 phyla.
      While much of these deeper habitats consisted of soft sediment and cobble, in
      rocky habitats, echinoderms, mollusks, bryozoans, and sponges were common. The
      southern hagfish (Myxine australis) was the most frequently encountered of the
      deep-sea fishes (50% of deployments), and while the Fueguian sprat (Sprattus
      fuegensis) was the most abundant fish species, its distribution was patchy. The
      Cape Horn and Diego Ramirez archipelagos represent some of the last intact sub
      Antarctic ecosystems remaining and a recently declared large protected area will
      help ensure the health of this unique region.

PMID- 29364903
TI  - Novel Naja atra cardiotoxin 1 (CTX-1) derived antimicrobial peptides with broad
      spectrum activity.
AB  - Naja atra subsp. atra cardiotoxin 1 (CTX-1), produced by Chinese cobra snakes,
      belonging to Elapidae family, is included in the three-finger toxin family and
      exerts high cytotoxicity and antimicrobial activity too. Using as template mainly
      the tip and the subsequent beta-strand of the first "finger" of this toxin,
      different sequences of 20 amino acids linear peptides have been designed in order
      to avoid toxic effects but to maintain or even strengthen the partial
      antimicrobial activity already seen for the complete toxin. As a result, the
      sequence NCP-0 (Naja Cardiotoxin Peptide-0) was designed as ancestor and
      subsequently 4 other variant sequences of NCP-0 were developed. These synthesized
      variant sequences have shown microbicidal activity towards a panel of reference
      and field strains of Gram-positive and Gram-negative bacteria. The sequence named
      NCP-3, and its variants NCP-3a and NCP-3b, have shown the best antimicrobial
      activity, together with low cytotoxicity against eukaryotic cells and low
      hemolytic activity. Bactericidal activity has been demonstrated by minimum
      bactericidal concentration (MBC) assay at values below 10 MUg/ml for most of the
      tested bacterial strains. This potent antimicrobial activity was confirmed even
      for unicellular fungi Candida albicans, Candida glabrata and Malassezia
      pachydermatis (MBC 50-6.3 MUg/ml), and against the fast-growing mycobacteria
      Mycobacterium smegmatis and Mycobacterium fortuitum. Moreover, NCP-3 has shown
      virucidal activity on Bovine Herpesvirus 1 (BoHV1) belonging to Herpesviridae
      family. The bactericidal activity is maintained even in a high salt concentration
      medium (125 and 250 mM NaCl) and phosphate buffer with 20% Mueller Hinton (MH)
      medium against E. coli, methicillin resistant Staphylococcus aureus (MRSA) and
      Pseudomonas aeruginosa reference strains. Considering these in vitro obtained
      data, the search for active sequences within proteins presenting an intrinsic
      microbicidal activity could provide a new way for discovering a large number of
      novel and promising antimicrobial peptides families.

PMID- 29364904
TI  - Development of an activity-based probe for acyl-protein thioesterases.
AB  - Protein palmitoylation is a dynamic post-translational modification (PTM)
      important for cellular functions such as protein stability, trafficking,
      localization, and protein-protein interactions. S-palmitoylation occurs via the
      addition of palmitate to cysteine residues via a thioester linkage, catalyzed by
      palmitoyl acyl transferases (PATs), with removal of the palmitate catalyzed by
      acyl protein thioesterases (APTs) and palmitoyl-protein thioesterases (PPTs).
      Tools that target the regulators of palmitoylation-PATs, APTs and PPTs-will
      improve understanding of this essential PTM. Here, we describe the synthesis and
      application of a cell-permeable activity-based probe (ABP) that targets APTs in
      intact mammalian cells and the parasite Toxoplasma gondii. Using a focused
      library of substituted chloroisocoumarins, we identified a probe scaffold with
      nanomolar affinity for human APTs (HsAPT1 and HsAPT2) and synthesized a
      fluorescent ABP, JCP174-BODIPY TMR (JCP174-BT). We use JCP174-BT to profile HsAPT
      activity in situ in mammalian cells, to detect an APT in T. gondii (TgPPT1). We
      show discordance between HsAPT activity levels and total protein concentration in
      some cell lines, indicating that total protein levels may not be representative
      of APT activity in complex systems, highlighting the utility of this probe.

PMID- 29364905
TI  - A wolf in sheep's clothing: The description of a fly resembling jumping spider of
      the genus Scoturius Simon, 1901 (Araneae: Salticidae: Huriini).
AB  - Fly resemblance in arthropods is much less common than e.g., resemblance to ants
      or wasps, and has been mainly observed in beetles. Putative fly mimicry in
      arachnids has been reported only from the jumping spider genus Saitis. However,
      recent literature has attributed the fly-resembling characteristics in Saitis to
      sexual signalling during courtship. The lack of observation of fly mimicry in
      spiders is not surprising as flies belong to the most important prey item group
      of spiders. In this study, a new fly-resembling species of the jumping spider
      tribe Huriini, Scoturius dipterioides sp. nov., from the pre-Andean Chiquitano
      forest at the Bolivian orocline is described and illustrated. The new species was
      tentatively placed into Scoturius because the epigynum has a single large
      elliptical opening. Scoturius dipterioides sp. nov. is distinguished from all
      other species of this tribe by a combination of following characteristics:
      epigynum with a large anterior elliptical atrium and initial portion of the
      copulation ducts dilated as a chamber (shared with Urupuyu); relatively joined
      copulation openings and short copulation ducts; kidney-shaped spermathecae,
      advanced at the atrium level. Several somatic features, two of them found
      exclusively in S. dipterioides sp. nov., increase the resemblance to flies. The
      Huriini are currently the only spider tribe that is suggested to feature fly
      mimics.

PMID- 29364906
TI  - A natural human monoclonal antibody targeting Staphylococcus Protein A protects
      against Staphylococcus aureus bacteremia.
AB  - Staphylococcus aureus can cause devastating and life-threatening infections. With
      the increase in multidrug resistant strains, novel therapies are needed. Limited
      success with active and passive immunization strategies have been attributed to
      S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that
      circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety
      Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their
      Fc region, neutralizing effector function. The organism can thus shield itself
      with a protective coat of serum antibodies and render humoral immunity
      ineffective. The present antibody reactivity was derived from an individual with
      natural anti-SpA antibody titers. The monoclonal antibody is of an IgG3 subclass,
      which differs critically from other immunoglobulin subclasses since its Fc is not
      bound by SpA. Moreover, it targets a unique epitope on SpA that allows it to bind
      in the presence of serum antibodies. Consequently, the antibody opsonizes S.
      aureus and maintains effector function to enable natural immune mediated
      clearance. The data presented here provide evidence that 514G3 antibody is able
      to successfully rescue mice from S. aureus mediated bacteremia.

PMID- 29364907
TI  - HPV integration hijacks and multimerizes a cellular enhancer to generate a viral
      cellular super-enhancer that drives high viral oncogene expression.
AB  - Integration of human papillomavirus (HPV) genomes into cellular chromatin is
      common in HPV-associated cancers. Integration is random, and each site is unique
      depending on how and where the virus integrates. We recently showed that tandemly
      integrated HPV16 could result in the formation of a super-enhancer-like element
      that drives transcription of the viral oncogenes. Here, we characterize the
      chromatin landscape and genomic architecture of this integration locus to
      elucidate the mechanisms that promoted de novo super-enhancer formation. Using
      next-generation sequencing and molecular combing/fiber-FISH, we show that ~26
      copies of HPV16 are integrated into an intergenic region of chromosome 2p23.2,
      interspersed with 25 kb of amplified, flanking cellular DNA. This interspersed,
      co-amplified viral-host pattern is frequent in HPV-associated cancers and here we
      designate it as Type III integration. An abundant viral-cellular fusion
      transcript encoding the viral E6/E7 oncogenes is expressed from the integration
      locus and the chromatin encompassing both the viral enhancer and a region in the
      adjacent amplified cellular sequences is strongly enriched in the super-enhancer
      markers H3K27ac and Brd4. Notably, the peak in the amplified cellular sequence
      corresponds to an epithelial-cell-type specific enhancer. Thus, HPV16 integration
      generated a super-enhancer-like element composed of tandem interspersed copies of
      the viral upstream regulatory region and a cellular enhancer, to drive high
      levels of oncogene expression.

PMID- 29364908
TI  - Landscapes with different biodiversity influence distribution of small mammals
      and their ectoparasitic chigger mites: A comparative study from southwest China.
AB  - From a previous field investigation in Yunnan, southwest China between 2001 and
      2015, we selected two types of landscapes to make a retrospectively comparative
      study on the distribution of small mammals and their ectoparasitic chigger mites.
      One landscape is "mountainous uncultivated land (MUL)" with higher biodiversity,
      which is located in a famous "World Nature Heritage Site", the Three-Parallel
      Rivers Region in the northwest of Yunnan. The other is "cultivated flatland
      landscape (CFL)" with lower biodiversity, which is located in the south of
      Yunnan. The landscapes with different biodiversity apparently influenced the
      distribution of small mammals and their ectoparasitic chigger mites. Much more
      species of small mammals and mites were found in MUL than in CFL. A total of
      3,177 small mammals captured from MUL were identified as 55 species, 30 genera
      and 10 families in five orders. From these small mammal hosts, 5,882 chigger
      mites were collected and identified as 127 species, 15 genera and 3 subfamilies
      in two families. A total of 1,112 small mammals captured from CFL were identified
      as 19 species, 12 genera and 5 families in three orders. From these hosts, 17,742
      chiggers were collected and identified as 86 species, 12 genera and 3 subfamilies
      in two families. Both the species diversity (S = 55) and community diversity (H =
      2.673) of small mammals in MUL were much higher than those in CFL (S = 19; H =
      0.926). There were also higher values of beta diversity in MUL than in CFL.
      Different main reservoir rodent hosts of zoonoses (including tsutsugamushi
      disease) were found in two types of landscapes. Rattus tanezumi (one main
      reservoir host) was most abundant in CFL, which accounted for 80.22% of all the
      small mammals. Another two main reservoir hosts, Eothenomys miletus and Apodemus
      chevrieri were the dominant species in MUL, but they were not as abundant as R.
      tanezumi in CFL. Different vector species of chigger mites also existed in MUL
      and CFL. Leptotrombidium deliense (a main and powerful vector of tsutsugamushi
      disease in China) and Ascoschoengastia indica (a potential vector of
      tsutsugamushi disease) were the dominant species of chigger mites in CFL (Cr =
      25.81% for A. indica; Cr = 23.47% for L. deliense). Leptotrombidium scutellare
      (also a main vector of tsutsugamushi disease in China) was the dominant chigger
      species in MUL (Cr = 26.09%). Higher infestation of vector mites on small mammals
      was found in the simple landscape with lower biodiversity (CFL) than in the
      complex landscape with higher biodiversity (MUL). The overall prevalence (P),
      mean abundance (MA) and mean intensity (MI) of chigger mites on small mammals
      were much higher in CFL than in MUL. The main vector mite species on their main
      rodent hosts also showed a higher P, MA and MI in CFL than in MUL.

PMID- 29364909
TI  - Intestinal fibrosis is associated with lack of response to Infliximab therapy in
      Crohn's disease.
AB  - INTRODUCTION: Overt fibrostenotic disease is a relative contraindication for anti
      TNF therapy in Crohn's disease. We hypothesized that subclinical fibrosis may
      also contribute to an incomplete response to anti-TNF therapy before the onset of
      symptomatic stenosis. METHODS: In a previous trial, patients with ileocecal
      Crohn's disease were randomized to either immediate ileocecal resection or
      medical treatment with Infliximab. In case of insufficient response to
      Infliximab, the latter underwent secondary ileocecal resection. We compared
      specimens from those patients undergoing immediate resection (Infliximab naive, n
      = 20) to those who failed Infliximab therapy (n = 20). RESULTS: Infliximab naive
      and Infliximab failure patients had similar severity of inflammation when
      assessed by CRP levels (median 14 vs 9 mg/L) and histology (Geboes-D'Haens-score,
      median 10 vs 11 points). On immunohistochemistry, collagen-III and fibronectin
      depositions were increased in patients previously exposed to Infliximab compared
      to patients naive to Infliximab. On mRNA level, procollagen peptidase showed
      significantly more mucosal mRNA expression in Crohn's disease patients who failed
      Infliximab. Infliximab responders showed no increase of this marker after 4 weeks
      of successful Infliximab treatment. DISCUSSION: Failure to Infliximab therapy is
      associated with subclinical fibrosis in Crohn's disease.

PMID- 29364910
TI  - Climatic shocks associate with innovation in science and technology.
AB  - Human history is shaped by landmark discoveries in science and technology.
      However, across both time and space the rate of innovation is erratic: Periods of
      relative inertia alternate with bursts of creative science and rapid cascades of
      technological innovations. While the origins of the rise and fall in rates of
      discovery and innovation remain poorly understood, they may reflect adaptive
      responses to exogenously emerging threats and pressures. Here we examined this
      possibility by fitting annual rates of scientific discovery and technological
      innovation to climatic variability and its associated economic pressures and
      resource scarcity. In time-series data from Europe (1500-1900CE), we indeed found
      that rates of innovation are higher during prolonged periods of cold (versus
      warm) surface temperature and during the presence (versus absence) of volcanic
      dust veils. This negative temperature-innovation link was confirmed in annual
      time-series for France, Germany, and the United Kingdom (1901-1965CE). Combined,
      across almost 500 years and over 5,000 documented innovations and discoveries, a
      0.5 degrees C increase in temperature associates with a sizable 0.30-0.60
      standard deviation decrease in innovation. Results were robust to controlling for
      fluctuations in population size. Furthermore, and consistent with economic theory
      and micro-level data on group innovation, path analyses revealed that the
      relation between harsher climatic conditions between 1500-1900CE and more
      innovation is mediated by climate-induced economic pressures and resource
      scarcity.

PMID- 29364912
TI  - Left atrial emptying fraction predicts recurrence of atrial fibrillation after
      radiofrequency catheter ablation.
AB  - BACKGROUND: Compared with left atrial (LA) dimension, LA emptying fraction (LAEF)
      has received less emphasis as a predictor of atrial fibrillation (AF) recurrence
      after radiofrequency catheter ablation (RFCA). In addition, patients experiencing
      post-RFCA AF recurrence may respond to previously ineffective antiarrhythmic
      drugs (AADs). Classifying these patients into a third RFCA outcome category is
      recommended. OBJECTIVE: To identify predictors of RFCA outcome classified into
      three categories, and to build proportional odds logistic regression models for
      clinical applicability to predict AF recurrence. METHODS: Data were
      retrospectively collected from 483 consecutive patients with drug-refractory AF
      undergoing RFCA (328 men; age 58.4 +/- 11.5 years; 383 paroxysmal). Patients were
      classified into 3 groups based on the last RFCA outcome: group 1, free from AF
      without AADs; group 2, free from AF with AADs; and group 3, recurrence of AADs
      refractory atrial tachyarrhythmia. RESULTS: After a mean follow-up duration of
      64.5 +/- 43.2 months and mean ablation procedure number of 1.37 +/- 0.68, the
      RFCA outcome showed 76.0%, 9.5% and 14.5% of patients in groups 1, 2, and 3,
      respectively. In multivariate analysis, LAEF was the most stable and important
      predictor of AF recurrence, followed by body mass index, stroke, AF duration,
      mitral regurgitation, and LA linear ablation. For patients undergoing repeat
      RFCA, LAEF was the only independent predictor (cutoffs: 43% and 35% for groups 1
      and 3, respectively). CONCLUSION: LAEF provides optimal prognostic information
      regarding the risk stratification of AF patients undergoing RFCA.

PMID- 29364911
TI  - Scholastic performance and functional connectivity of brain networks in children.
AB  - One of the keys to understanding scholastic success is to determine the neural
      processes involved in school performance. The present study is the first to use a
      whole-brain connectivity approach to explore whether functional connectivity of
      resting state brain networks is associated with scholastic performance in seventy
      four 7- to 9-year-old children. We demonstrate that children with higher
      scholastic performance across reading, math and language have more integrated and
      interconnected resting state networks, specifically the default mode network,
      salience network, and frontoparietal network. To add specificity, core regions of
      the dorsal attention and visual networks did not relate to scholastic
      performance. The results extend the cognitive role of brain networks in children
      as well as suggest the importance of network connectivity in scholastic success.

PMID- 29364914
TI  - Relation of body mass index to risk of developing inflammatory bowel disease
      amongst women in the Danish National Birth Cohort.
AB  - BACKGROUND: Crohn's disease (CD) has traditionally been associated with weight
      loss and low BMI, yet paradoxically obesity has recently been suggested as a risk
      factor for CD, but not for ulcerative colitis (UC). We therefore hypothesized
      that the relation between BMI and CD is U shaped. AIM: To conduct a large
      population-based prospective cohort study of BMI and later risk of IBD, taking
      age at IBD diagnosis into account. METHODS: A cohort of 74,512 women from the
      Danish National Birth Cohort, with BMI measured pre-pregnancy and 18 months after
      delivery, was followed for 1,022,250 person-years for development of IBD,
      according to the Danish National Patient Register. Associations were tested by
      Cox regression. RESULTS: Overweight subjects (25<=BMI<30 kg/m2) had the lowest
      risk of CD, whereas obesity (BMI>=30kg/m2) increased the risk of CD at all ages,
      and low BMI (BMI<18.5kg/m2) associated with CD diagnosed at age 18-<40 years.
      Hence, using normal weight subjects as the reference, adjusted HRs for risk of
      developing CD (at age 18-<40 years) were 1.8(95%CI, 0.9-3.7) for underweight,
      0.6(0.3-1.2) for overweight, and 1.5(0.8-2.7) for obese individuals (pre
      pregnancy BMI). HRs were greater for BMI determined 18 months after delivery.
      Splines for CD risk according to waist:height ratio confirmed a U-shaped
      relationship with CD occurring <40 years, and a linear relationship with CD
      diagnosed at age 40+. There was no relationship between BMI and risk of UC.
      CONCLUSION: For the first time, we demonstrate that both high BMI and low BMI are
      risk factors for CD. Underweight may be a pre-clinical manifestation of disease
      being present many years before onset with obesity being a true risk factor. This
      raises the question as to whether there may be two distinct forms of CD.

PMID- 29364915
TI  - Helicobacter pylori moderates the association between 5-MTHF concentration and
      cognitive function in older adults.
AB  - OBJECTIVE: To explore potential interactions between folate-cycle factors and
      Helicobacter pylori seropositivity in the prediction of cognitive function.
      METHODS: We used data obtained from the 1999-2000 continuous National Health and
      Nutrition Examination Survey produced by the United States' Centers for Disease
      Control and Prevention. Using Ordinary Least Squares regression, we tested for
      associations between multiple folate-cycle factors, Helicobacter pylori
      seropositivity, and cognitive function assessed by the digit symbol coding
      subtest of the Wechsler Adult Intelligence Scale-III. We then tested for
      interactions between each of the folate-cycle factors and Helicobacter pylori in
      the prediction of cognitive function. RESULTS: Although Helicobacter pylori
      seropositivity, 5-methyltetrahydrofolate, vitamin B-12, and homocysteine were not
      associated with performance on the digit symbol coding task, Helicobacter pylori
      seropositivity interacted with 5-methyltetrahydrofolate concentration to predict
      performance on the digit symbol coding task. The Helicobacter pylori seropositive
      group performed worse on the digit symbol coding task as 5-methyltetrahydrofolate
      concentration decreased. CONCLUSION: The interaction between Helicobacter pylori
      seropositivity and reduced folate-cycle factor 5-methyltetrahydrofolate might
      impair aspects of cognitive function.

PMID- 29364913
TI  - Effect of different levels of feed restriction and fish oil fatty acid
      supplementation on fat deposition by using different techniques, plasma levels
      and mRNA expression of several adipokines in broiler breeder hens.
AB  - BACKGROUND: Reproductive hens are subjected to a restricted diet to limit the
      decline in fertility associated with change in body mass. However, endocrine and
      tissue responses to diet restriction need to be documented. OBJECTIVE: We
      evaluated the effect of different levels of feed restriction, with or without
      fish oil supplementation, on metabolic parameters and adipokine levels in plasma
      and metabolic tissues of reproductive hens. METHODS: We designed an in vivo
      protocol involving 4 groups of hens; RNS: restricted (Rt) unsupplemented, ANS: ad
      libitum (Ad, receiving an amount of feed 1.7 times greater than animals on the
      restricted diet) unsupplemented, RS: Rt supplemented, and AS: Ad supplemented.
      The fish oil supplement was used at 1% of the total diet composition. RESULTS:
      Hens fed with the Rt diet had a significantly (P < 0.0001) lower growth than Ad
      hens, while the fish oil supplementation had no effect on these parameters.
      Furthermore, the bioelectrical impedance analysis (BIA) and the fat
      ultrasonographic examinations produced similar results to the other methods that
      required animals to be killed (carcass analysis and weight of adipose tissue). In
      addition, the Rt diet significantly (P < 0.05) decreased plasma levels of
      triglycerides, phospholipids, glucose and ADIPOQ, and fish oil supplementation
      decreased plasma levels of RARRES2. We also showed a positive correlation between
      insulin values and ADIPOQ or NAMPT or RARRES2 values, and a negative correlation
      of fat percentage to RARRES2 values. Moreover, the effects of the Rt diet and
      fish oil supplementation on the mRNA expression depended on the factors tested
      and the hen age. CONCLUSIONS: Rt diet and fish oil supplementation are able to
      modulate metabolic parameters and the expression of adipokines and their
      receptors in metabolic tissue.

PMID- 29364916
TI  - Coexistence of coyotes (Canis latrans) and red foxes (Vulpes vulpes) in an urban
      landscape.
AB  - Urban environments are increasing worldwide and are inherently different than
      their rural counterparts, with a variety of effects on wildlife due to human
      presence, increased habitat fragmentation, movement barriers, and access to
      anthropogenic food sources. Effective management of urban wildlife requires an
      understanding of how urbanization affects their behavior and ecology. The spatial
      activity and interactions of urban wildlife, however, have not been as rigorously
      researched as in rural areas. From January 2015 to December 2016, we captured,
      radio-collared, and tracked 11 coyotes and 12 red foxes in Madison, WI. Within
      our study area, coyotes strongly selected home ranges with high proportions of
      natural areas; conversely, red foxes selected home ranges with open space and
      moderately developed areas. Use of highly developed areas best explained
      variation among individual home range sizes and inversely affected home range
      size for coyotes and red foxes. Coyote and red fox home ranges showed some degree
      of spatial and temporal overlap, but generally appeared partitioned by habitat
      type within our study area. Coyotes and red foxes were both active at similar
      times of the day, but their movement patterns differed based on species-specific
      habitat use. This spatial partitioning may promote positive co-existence between
      these sympatric canids in urban areas, and our findings of spatial activity and
      interactions will better inform wildlife managers working in urban areas.

PMID- 29364917
TI  - Motivational power of future time perspective: Meta-analyses in education, work,
      and health.
AB  - Future time perspective (FTP) may predict individual attitudes and behaviors.
      However, FTP research includes different FTP conceptualizations and outcomes
      which hinder generalizing its findings. To solve the inconsistencies in FTP
      research and generalize the magnitude of FTP as a driver of motivation and
      behavior, we conducted the first systematical synthesis of FTP relationships in
      three crucial life domains. Our meta-analyses of FTP studies in education (k =
      28), work (k = 17), and health (k = 32) involved N = 31,558 participants, and
      used a conceptual model for grouping FTP constructs. To address different outcome
      types, we applied the Theory of Planned Behavior when coding the studies. FTP
      relationships with outcomes were small-to-medium, were generalizable across
      domains, and were strongest when the FTP construct included a mixture of
      cognition, behavioral intention, and affect and, in education, when the FTP
      measure was domain specific rather than general. There were cross-cultural
      differences in FTP-outcome relationships. The strength of the FTP-outcome types
      relationship varied for attitudes, perceived behavioral control, behavioral
      intention, and behaviors. The lowest effect sizes were found for FTP predicting
      actual behaviors in education, work, and health and between FTP and health
      attitudes. Theoretical implications of the findings and future research
      directions are discussed.

PMID- 29364918
TI  - Riociguat versus sildenafil on hypoxic pulmonary vasoconstriction and
      ventilation/perfusion matching.
AB  - INTRODUCTION: Current treatment with vasodilators for pulmonary hypertension
      associated with respiratory diseases is limited by their inhibitory effect on
      hypoxic pulmonary vasoconstriction (HPV) and uncoupling effects on ventilation
      perfusion (V'/Q'). Hypoxia is also a well-known modulator of the nitric oxide
      (NO) pathway, and may therefore differentially affect the responses to
      phosphodiesterase 5 (PDE5) inhibitors and soluble guanylyl cyclase (sGC)
      stimulators. So far, the effects of the sGC stimulator riociguat on HPV have been
      poorly characterized. MATERIALS AND METHODS: Contraction was recorded in
      pulmonary arteries (PA) in a wire myograph. Anesthetized rats were catheterized
      to record PA pressure. Ventilation and perfusion were analyzed by micro-CT-SPECT
      images in rats with pulmonary fibrosis induced by bleomycin. RESULTS: The PDE5
      inhibitor sildenafil and the sGC stimulator riociguat similarly inhibited HPV in
      vitro and in vivo. Riociguat was more effective as vasodilator in isolated rat
      and human PA than sildenafil. Riociguat was ~3-fold more potent under hypoxic
      conditions and it markedly inhibited HPV in vivo at a dose that barely affected
      the thromboxane A2 (TXA2) mimetic U46619-induced pressor responses. Pulmonary
      fibrosis was associated with V'/Q' uncoupling and riociguat did not affect the
      V'/Q' ratio. CONCLUSION: PDE5 inhibitors and sGC stimulators show a different
      vasodilator profile. Riociguat was highly effective and potentiated by hypoxia in
      rat and human PA. In vivo, riociguat preferentially inhibited hypoxic than non
      hypoxic vasoconstriction. However, it did not worsen V'/Q' coupling in a rat
      model of pulmonary fibrosis.

PMID- 29364919
TI  - Genome-wide analyses of the Bemisia tabaci species complex reveal contrasting
      patterns of admixture and complex demographic histories.
AB  - Once considered a single species, the whitefly, Bemisia tabaci, is a complex of
      numerous morphologically indistinguishable species. Within the last three
      decades, two of its members (MED and MEAM1) have become some of the world's most
      damaging agricultural pests invading countries across Europe, Africa, Asia and
      the Americas and affecting a vast range of agriculturally important food and
      fiber crops through both feeding-related damage and the transmission of numerous
      plant viruses. For some time now, researchers have relied on a single
      mitochondrial gene and/or a handful of nuclear markers to study this species
      complex. Here, we move beyond this by using 38,041 genome-wide Single Nucleotide
      Polymorphisms, and show that the two invasive members of the complex are closely
      related species with signatures of introgression with a third species (IO). Gene
      flow patterns were traced between contemporary invasive populations within MED
      and MEAM1 species and these were best explained by recent international trade.
      These findings have profound implications for delineating the B. tabaci species
      status and will impact quarantine measures and future management strategies of
      this global pest.

PMID- 29364920
TI  - Correlated microtiming deviations in jazz and rock music.
AB  - Musical rhythms performed by humans typically show temporal fluctuations. While
      they have been characterized in simple rhythmic tasks, it is an open question
      what is the nature of temporal fluctuations, when several musicians perform music
      jointly in all its natural complexity. To study such fluctuations in over 100
      original jazz and rock/pop recordings played with and without metronome we
      developed a semi-automated workflow allowing the extraction of cymbal beat onsets
      with millisecond precision. Analyzing the inter-beat interval (IBI) time series
      revealed evidence for two long-range correlated processes characterized by power
      laws in the IBI power spectral densities. One process dominates on short
      timescales (t < 8 beats) and reflects microtiming variability in the generation
      of single beats. The other dominates on longer timescales and reflects slow tempo
      variations. Whereas the latter did not show differences between musical genres
      (jazz vs. rock/pop), the process on short timescales showed higher variability
      for jazz recordings, indicating that jazz makes stronger use of microtiming
      fluctuations within a measure than rock/pop. Our results elucidate principles of
      rhythmic performance and can inspire algorithms for artificial music generation.
      By studying microtiming fluctuations in original music recordings, we bridge the
      gap between minimalistic tapping paradigms and expressive rhythmic performances.

PMID- 29364922
TI  - Correction: FGF Signalling Regulates Chromatin Organisation during Neural
      Differentiation via Mechanisms that Can Be Uncoupled from Transcription.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1003614.].

PMID- 29364921
TI  - Luteal and hypophyseal expression of the canine relaxin (RLN) system during
      pregnancy: Implications for luteotropic function.
AB  - By acting through its receptors (RXFP1, RXFP2), relaxin (RLN) exerts species
      specific effects during pregnancy; possible luteotropic effects through
      stimulation of prolactin (PRL) release have been suggested. In the domestic dog
      (Canis lupus familiaris) serum PRL increases in pregnant bitches shortly after
      RLN appears in the circulation, and a possible functional relationship between
      the RLN and the PRL systems in regulating progesterone secretion has been
      implied. Therefore, here (Study 1) the luteal expression and localization of the
      RLN system was investigated by immunohistochemistry using custom-made antibodies
      and semi-quantitative PCR, at selected time points during gestation: pre
      implantation (d. 8-12), post-implantation (d. 18-25), mid-gestation (d. 35-40)
      and at normal and antigestagen-induced luteolysis. Further, (Study 2) hypophyseal
      expression of the RLN system and its spatial association with PRL was assessed.
      Luteal expression of RLN, but not of its receptors, was time-dependent: it
      increased significantly following implantation towards mid-gestation and
      decreased at prepartum. Antigestagen treatment resulted in downregulation of RLN
      and RXFP2. Whereas RLN was localized in steroidogenic cells, RXFP1 and RXFP2 also
      stained strongly in macrophages and vascular endothelial cells. The RLN system
      was detected in the canine adenohypophysis and was co-localized with PRL in
      hypophyseal lactotrophs. The intraluteal RLN seems to be involved in regulating
      the canine corpus luteum (CL) in a time-dependent manner. The presence of RLN
      family members in the adenohypophysis implies their possible involvement in
      regulating the availability of PRL and other pituitary hormones.

PMID- 29364923
TI  - The clinical impact of bacteremia on outcomes in elderly patients with
      pyelonephritis or urinary sepsis: A prospective multicenter study.
AB  - BACKGROUND: Bacteremia is common in severe urinary infections, but its influence
      on the outcomes is not well established. The aim of this study was to assess the
      association of bacteremia with outcomes in elderly patients admitted to hospital
      with pyelonephritis or urinary sepsis. METHODS: This prospective muticenter
      observational study was conducted at 5 Spanish hospitals. All patients aged >65
      years with pyelonephritis or urinary sepsis admitted to the departments of
      internal medicine and with urine and blood cultures obtained at admission to
      hospital were eligible. Transfer to ICU, length of hospital stay, hospital
      mortality and all cause 30-day mortality in bacteremic and non-bacteremic groups
      were compared. Risk factors for all cause 30-day mortality was also estimated.
      RESULTS: Of the 424 patients included in the study 181 (42.7%) had bacteremia.
      Neither transfer to ICU (4.4% vs. 2.9%, p = 0.400), nor length of hospital stay
      (9.7+/-4.6 days vs. 9.0+/-7.3 days, p = 0.252), nor hospital mortality (3.3% vs.
      6.2%, p = 0.187), nor all cause 30-day mortality (9.4% vs. 13.2%, p = 0.223) were
      different between bacteremic and non-bacteremic groups. By multivariate analysis,
      risk factors for all cause 30-day mortality were age (OR 1.05, 95% CI 1.00-1.10),
      McCabe index >=2 (OR 10.47, 95% CI 2.96-37.04) and septic shock (OR 8.56, 95% CI
      2.86-25.61); whereas, bacteremia was inversely associated with all cause 30-day
      mortality (OR 0.33, 95% CI 0.15-0.71). CONCLUSIONS: In this cohort, bacteremia
      was not associated with a worse prognosis in elderly patients with pyelonephritis
      or urinary sepsis.

PMID- 29364924
TI  - Adipose tissue depot volume relationships with spinal trabecular bone mineral
      density in African Americans with diabetes.
AB  - Changes in select adipose tissue volumes may differentially impact bone mineral
      density. This study was performed to assess cross-sectional and longitudinal
      relationships between computed tomography-determined visceral (VAT), subcutaneous
      (SAT), inter-muscular (IMAT), and pericardial adipose tissue (PAT) volumes with
      respective changes in thoracic vertebral and lumbar vertebral volumetric
      trabecular bone mineral density (vBMD) in African Americans with type 2 diabetes.
      Generalized linear models were fitted to test relationships between baseline and
      change in adipose volumes with change in vBMD in 300 African American-Diabetes
      Heart Study participants; adjustment was performed for age, sex, diabetes
      duration, study interval, smoking, hypertension, BMI, kidney function, and
      medications. Participants were 50% female with mean +/- SD age 55.1+/-9.0 years,
      diabetes duration 10.2+/-7.2 years, and BMI 34.7+/-7.7 kg/m2. Over 5.3 +/- 1.4
      years, mean vBMD decreased in thoracic/lumbar spine, while mean adipose tissue
      volumes increased in SAT, IMAT, and PAT, but not VAT depots. In fully-adjusted
      models, changes in lumbar and thoracic vBMD were positively associated with
      change in SAT (beta[SE] 0.045[0.011], p<0.0001; 0.40[0.013], p = 0.002,
      respectively). Change in thoracic vBMD was positively associated with change in
      IMAT (p = 0.029) and VAT (p = 0.016); and change in lumbar vBMD positively
      associated with baseline IMAT (p<0.0001). In contrast, vBMD was not associated
      with change in PAT. After adjusting for BMI, baseline and change in volumes of
      select adipose depots were associated with increases in thoracic and lumbar
      trabecular vBMD in African Americans. Effects of adiposity on trabecular bone
      appear to be site-specific and related to factors beyond mechanical load.

PMID- 29364925
TI  - The predictive value of bedside ultrasound to restore spontaneous circulation in
      patients with pulseless electrical activity: A systematic review and meta
      analysis.
AB  - BACKGROUND: The prognosis of pulseless electrical activity is dismal. However, it
      is still challengable to decide when to terminate or continue resuscitation
      efforts. The aim of this study was to determine whether the use of bedside
      ultrasound (US) could predict the restoration of spontaneous circulation (ROSC)
      in patients with pulseless electrical activity (PEA) through the identification
      of cardiac activity. METHODS: This was a systematic review and meta-analysis of
      studies that used US to predict ROSC. A search of electronic databases (Cochrane
      Central, MEDLINE, EMBASE) was conducted up to June 2017, and the assessment of
      study quality was performed with the Newcastle-Ottawa Scale. Statistical analysis
      was performed with Review Manager 5.3 and Stata 12. RESULTS: Eleven studies that
      enrolled a total of 777 PEA patients were included. A total of 230 patients
      experienced ROSC. Of these, 188 had sonographically identified cardiac activity
      (pseudo-PEA). A meta-analysis showed that PEA patients with cardiac activity on
      US were more likely to obtain ROSC compared to those with cardiac standstill:
      risk ratio (RR) = 4.35 (95% confidence interval [CI], 2.20-8.63; p<0,00001) with
      significant statistical heterogeneity (I2 = 60%). Subgroup analyses were
      conducted: US evaluation using only on the subxiphoid view: RR = 1.99 (95% CI,
      0.79-5.02; p = 0.15); evaluation using various views: RR = 4.09 (95% CI,2.70
      6.02; p<0.00001). CONCLUSIONS: In cardiac arrest patients who present with PEA,
      bedside US has an important role in predicting ROSC. The presence of cardiac
      activity in PEA patients may encourage more aggressive resuscitation.

PMID- 29364926
TI  - Bias due to differential participation in case-control studies and review of
      available approaches for adjustment.
AB  - OBJECTIVES: Low response rates in epidemiologic research potentially lead to the
      recruitment of a non-representative sample of controls in case-control studies.
      Problems in the unbiased estimation of odds ratios arise when characteristics
      causing the probability of participation are associated with exposure and
      outcome. This is a specific setting of selection bias and a realistic hazard in
      many case-control studies. This paper formally describes the problem and shows
      its potential extent, reviews existing approaches for bias adjustment applicable
      under certain conditions, compares and applies them. METHODS: We focus on two
      scenarios: a characteristic C causing differential participation of controls is
      linked to the outcome through its association with risk factor E (scenario I),
      and C is additionally a genuine risk factor itself (scenario II). We further
      assume external data sources are available which provide an unbiased estimate of
      C in the underlying population. Given these scenarios, we (i) review available
      approaches and their performance in the setting of bias due to differential
      participation; (ii) describe two existing approaches to correct for the bias in
      both scenarios in more detail; (iii) present the magnitude of the resulting bias
      by simulation if the selection of a non-representative sample is ignored; and
      (iv) demonstrate the approaches' application via data from a case-control study
      on stroke. FINDINGS: The bias of the effect measure for variable E in scenario I
      and C in scenario II can be large and should therefore be adjusted for in any
      analysis. It is positively associated with the difference in response rates
      between groups of the characteristic causing differential participation, and
      inversely associated with the total response rate in the controls. Adjustment in
      a standard logistic regression framework is possible in both scenarios if the
      population distribution of the characteristic causing differential participation
      is known or can be approximated well.

PMID- 29364927
TI  - Viral protein Nef is detected in plasma of half of HIV-infected adults with
      undetectable plasma HIV RNA.
AB  - OBJECTIVE: To address the role of translationally active HIV reservoir in chronic
      inflammation and non-AIDS related disorders, we first need a simple and accurate
      assay to evaluate viral protein expression in virally suppressed subjects.
      DESIGN: We optimized an HIV Nef enzyme-linked immunosorbent assay (ELISA) and
      used it to quantify plasma Nef levels as an indicator of the leaky HIV reservoir
      in an HIV-infected cohort. METHODS: This study accessed 134 plasma samples from a
      well-characterized cohort study of HIV-infected and uninfected adults in San
      Francisco (the SCOPE cohort). We optimized an ELISA for detection of plasma Nef
      in HIV-negative subjects and HIV-infected non-controllers, and evaluated its
      utility to quantify plasma Nef levels in a cross-sectional study of ART
      suppressed and elite controller HIV-infected subjects. RESULTS: Here, we describe
      the performance of an optimized HIV Nef ELISA. When we applied this assay to the
      study cohort we found that plasma Nef levels were correlated with plasma HIV RNA
      levels in untreated disease. However, we were able to detect Nef in plasma of
      approximately half of subjects on ART or with elite control, despite the lack of
      detectable plasma HIV RNA levels using standard assays. Plasma Nef levels were
      not consistently associated with CD4+ T-cell count, CD8+ T-cell count, self
      reported nadir CD4+ T-cell count or the CD4+/CD8+ T-cell ratio in HIV-infected
      subjects. CONCLUSION: Since plasma HIV RNA levels are undetectable in virally
      suppressed subjects, it is reasonable to assume that viral protein expression in
      leaky reservoir, and not plasma virions, is the source of Nef accumulating in
      plasma. To examine this further, improvements of the assay sensitivity, by
      lowering the background through improvements in the quality of Nef antibodies,
      and detailed characterization of the HIV reservoirs are needed.

PMID- 29364928
TI  - Prevalence and predictors of depressive symptoms among HIV-positive men who
      inject drugs in Vietnam.
AB  - BACKGROUND: HIV infection is common among people who inject drugs (PWID), and HIV
      positive PWID may be particularly vulnerable to depression. This study measured
      the prevalence of depressive symptoms and the factors associated with severe
      symptoms among 455 HIV-positive PWID in Thai Nguyen, Vietnam. METHODS: We used
      cross-sectional data from PWID in a randomized controlled trial of an
      intervention to reduce high-risk injecting and sexual behaviors in Thai Nguyen
      from 2009-2013. Depressive symptoms were measured with the Center for
      Epidemiologic Studies Depression Scale (CES-D). We used logistic regression to
      assess demographic, clinical, and psychosocial predictors of severe depressive
      symptoms (CES-D>=23) with prevalence odds ratios (POR) and 95% confidence
      intervals (CI). RESULTS: The prevalence of severe depressive symptoms (CES-D>=23)
      was 44%. 25% of participants had mild to moderate depressive symptoms (16<=CES
      D<23), and 31% experienced no depressive symptoms (CES-D<16). Not being married,
      self-rated poor health, greater frequency of injection drug use, history of
      overdose, no alcohol use, and daily cigarette smoking were positively associated
      with severe depressive symptoms in unadjusted models and remained predictive in a
      multivariable model. The strongest predictors of depressive symptoms were self
      reported poor health (POR = 2.94, 95% CI: 1.82, 4.76), no current alcohol use
      (POR = 2.35, 95% CI: 1.47, 3.77), and not currently married or cohabitating (POR
      = 2.21, 95% CI = 1.40, 3.47). CONCLUSION: Severe depressive symptoms were common
      among HIV-positive PWID in Thai Nguyen and were strongly associated with
      demographic, clinical, and psychosocial factors. Interventions that promote
      social support from family and reduce drug dependence may particularly benefit
      PWID experiencing severe depressive symptoms. Greater recognition and treatment
      of depressive symptoms has the potential to enhance quality of life and improve
      HIV clinical outcomes for PWID.

PMID- 29364929
TI  - Real-life effectiveness and safety of salbutamol Steri-NebTM vs. Ventolin
      Nebules(r) for exacerbations in patients with COPD: Historical cohort study.
AB  - INTRODUCTION: Ventolin Nebules(r) (reference product; GlaxoSmithKline) was the
      first licensed nebulizer solution containing the rapid-onset, short-acting beta2
      agonist salbutamol. Salbutamol Steri-NebTM (comparator; Teva Pharmaceuticals,
      Inc.) has the same chemical composition as the reference product. This study
      evaluated whether the effectiveness of the comparator is non-inferior to the
      reference product alongside concomitant medications during real-life clinical
      management of COPD exacerbations. Safety in terms of adverse events (AEs) was
      also examined. METHODS: This matched (1:1) historical cohort study evaluated data
      from 2 UK primary care databases on patients prescribed the salbutamol comparator
      or reference. The study included a 1-year baseline period, starting 1 year before
      the index prescription date, and 1-year outcome period. Cohorts were matched for
      baseline COPD respiratory medications. The primary outcome was analysis of non
      inferiority for the comparator versus reference product for the rate of moderate
      and severe COPD exacerbations. Non-inferiority was satisfied if the 95%
      confidence interval (CI) upper limit for mean differences in proportions between
      treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of
      severe exacerbations and AEs. RESULTS: After matching, 1191 patients were
      included in each cohort. Adjusted upper 95% CI for the difference in proportion
      of patients experiencing moderate or severe exacerbations between comparator and
      reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant
      differences were observed in rates of moderate and severe exacerbations (RR:
      1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17),
      or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders.
      No significant differences across cohorts were observed for rates of any AE or
      death. CONCLUSION: This matched cohort study of real-life management of COPD
      patients supports the salbutamol comparator as non-inferior to the reference
      product, providing an effective treatment alternative for COPD exacerbations.
      Comparator and reference safety profiles were similar.

PMID- 29364930
TI  - Detection of DNA oligonucleotides with base mutations by terahertz spectroscopy
      and microstructures.
AB  - DNA oligonucleotides with a 5-base mutation at the 3'-terminus were investigated
      by terahertz (THz) spectroscopy in a marker-free manner. The four single-stranded
      oligonucleotides with 17nt have been detected with specificity on a microfluidic
      chip, and corroborated by spectral measurements with split-ring resonators. The
      number of hydrogen bonds formed between the oligonucleotide and its surrounding
      water molecules, deemed a key contribution to the THz absorption of biological
      solutions, was explored by molecular dynamics simulations to explain the
      experimental findings. Our work underlies the feasibility of THz spectroscopy
      combined with microstructures for marker-free detection of DNA, which may form
      the basis of a prospective diagnostic tool for studying genic mutation.

PMID- 29364931
TI  - Object-based attention modulates the discrimination of level increments in stop
      consonant noise bursts.
AB  - This study tested the hypothesis that object-based attention modulates the
      discrimination of level increments in stop-consonant noise bursts. With consonant
      vowel-consonant (CvC) words consisting of an ~80-dB vowel (v), a pre-vocalic (Cv)
      and a post-vocalic (vC) stop-consonant noise burst (~60-dB SPL), we measured
      discrimination thresholds (LDTs) for level increments (DeltaL) in the noise
      bursts presented either in CvC context or in isolation. In the 2-interval 2
      alternative forced-choice task, each observation interval presented a CvC word
      (e.g., /paek/ /paek/), and normal-hearing participants had to discern DeltaL in
      the Cv or vC burst. Based on the linguistic word labels, the auditory events of
      each trial were perceived as two auditory objects (Cv-v-vC and Cv-v-vC) that
      group together the bursts and vowels, hindering selective attention to DeltaL. To
      discern DeltaL in Cv or vC, the events must be reorganized into three auditory
      objects: the to-be-attended pre-vocalic (Cv-Cv) or post-vocalic burst pair (vC
      vC), and the to-be-ignored vowel pair (v-v). Our results suggest that instead of
      being automatic this reorganization requires training, in spite of using familiar
      CvC words. Relative to bursts in isolation, bursts in context always produced
      inferior DeltaL discrimination accuracy (a context effect), which depended
      strongly on the acoustic separation between the bursts and the vowel, being much
      keener for the object apart from (post-vocalic) than for the object adjoining
      (pre-vocalic) the vowel (a temporal-position effect). Variability in CvC
      dimensions that did not alter the noise-burst perceptual grouping had minor
      effects on discrimination accuracy. In addition to being robust and persistent,
      these effects are relatively general, evincing in forced-choice tasks with one or
      two observation intervals, with or without variability in the temporal position
      of DeltaL, and with either fixed or roving CvC standards. The results lend
      support to the hypothesis.

PMID- 29364932
TI  - Prediction of movement intention using connectivity within motor-related network:
      An electrocorticography study.
AB  - Most brain-machine interface (BMI) studies have focused only on the active state
      of which a BMI user performs specific movement tasks. Therefore, models developed
      for predicting movements were optimized only for the active state. The models may
      not be suitable in the idle state during resting. This potential maladaptation
      could lead to a sudden accident or unintended movement resulting from prediction
      error. Prediction of movement intention is important to develop a more efficient
      and reasonable BMI system which could be selectively operated depending on the
      user's intention. Physical movement is performed through the serial change of
      brain states: idle, planning, execution, and recovery. The motor networks in the
      primary motor cortex and the dorsolateral prefrontal cortex are involved in these
      movement states. Neuronal communication differs between the states. Therefore,
      connectivity may change depending on the states. In this study, we investigated
      the temporal dynamics of connectivity in dorsolateral prefrontal cortex and
      primary motor cortex to predict movement intention. Movement intention was
      successfully predicted by connectivity dynamics which may reflect changes in
      movement states. Furthermore, dorsolateral prefrontal cortex is crucial in
      predicting movement intention to which primary motor cortex contributes. These
      results suggest that brain connectivity is an excellent approach in predicting
      movement intention.

PMID- 29364933
TI  - Long-term dietary replacement of fishmeal and fish oil in diets for rainbow trout
      (Oncorhynchus mykiss): Effects on growth, whole body fatty acids and intestinal
      and hepatic gene expression.
AB  - The effects of replacing fishmeal and fish oil with a plant-based diet were
      studied in juvenile (10g) and ongrowing (250-350g) rainbow trout from first
      feeding. Feed-related differences in the intestinal and hepatic transcriptome
      were examined in juveniles after 7 months of feeding at 7 degrees C. Based on
      microarray results obtained for juveniles, the expression of selected genes
      related to lipid, cholesterol and energy metabolisms, was assessed by RT-qPCR in
      ongrowing trout after 6 additional months of feeding at 17 degrees C. Plasma
      glucose and cholesterol, lipid content and fatty acid profile of whole body were
      analyzed at both stages. After 7 months at 7 degrees C, all juveniles reached the
      same body weight (10g), while at 13 months ongrowing fish fed the totally plant
      based diet exhibited lower body weight (234 vs 330-337g). Body lipid content was
      higher in juveniles fed the totally plant-based diet (13.2 vs 9.4-9.9%), and
      plasma cholesterol was about 2-times lower in trout fed the plant-based diets at
      both stages. Fatty acid profile mirrored that of the respective diet, with low
      proportions of long-chain n-3 polyunsaturated fatty acids in fish fed plant-based
      diets. Genes involved in protein catabolism, carbohydrate metabolism and
      trafficking were down-regulated in the intestines of juveniles fed the plant
      based diets. This was not true for ongrowing fish. Genes involved in lipid and
      cholesterol metabolisms were up-regulated in the livers of fish fed plant-based
      diets for both stages. In this study, feeding trout a totally plant-based diet
      from first-feeding affect a relatively low proportion of metabolism-related
      genes. In the longer term, when fish were reared at a higher temperature, only
      some of these changes were maintained (i.e. up-regulation of lipid/cholesterol
      metabolism). Although the plant-based diets tested in this study had no major
      deficiencies, small adjustments in the feed-formula are needed to further
      optimize growth performance while sparing marine resources.

PMID- 29364934
TI  - Least-detectable and age-related local in vivo bone remodelling assessed by time
      lapse HR-pQCT.
AB  - We previously developed an image analysis approach for the determination of local
      sites of bone remodelling using time-lapse in vivo HR-pQCT. The involved image
      filtering for removing noise was chosen rather aggressively, and also removed
      some effects of the bone remodelling. In this paper, we quantify these filtering
      settings using ex vivo reproducibility HR-pQCT images, and determine the least
      detectable bone remodelling using in vivo reproducibility HR-pQCT images, as well
      as testing whether the approach is capable of capturing age-related bone
      remodelling by use of in vivo long-term HR-pQCT images. We found that a threshold
      value of 225 mg HA/cm3 for the filtering led to acceptable results with falsely
      determined bone remodelling of less than 0.5%, and that the least-detectable bone
      formation and bone resorption are 2.0 +/- 1.0% and 2.2 +/- 0.7% respectively. We
      also found that age-related local bone remodelling can be captured satisfactorily
      in postmenopausal women. The latter revealed new insights into the effect of
      ageing on bone remodelling, and showed that bone remodelling seems to take place
      through a few small formation packets and many large resorption volumes leading
      to a net bone loss. We conclude that local in vivo bone remodelling can be
      successfully assessed with time-lapse in vivo HR-pQCT capable of assessing age
      related changes in bone remodelling.

PMID- 29364936
TI  - Empirical study of lane-changing behavior on three Chinese freeways.
AB  - Lane-changing (LC) behavior is investigated on Chinese freeways, where the
      driving circumstances are relatively aggressive. Three data sets were collected
      from urban expressways and an intercity highway in the form of traffic videos.
      Different aspects of LC behaviors are analyzed, i.e., the LC rate, motivation,
      target lane choice and impact on traffic. The results suggest that LC is a
      transient behavior that randomly occurs with high frequency, which is the main
      feature of aggressive driving. Several LC patterns and the combination effect of
      ramps, fast lanes and various vehicle types are presented. The influence of LC on
      local traffic endures for approximately 15 to 30 s, which rapidly increases and
      slowly declines. LC behavior will increase the risk of high-speed car-following.
      All results are obtained from the empirical data; they will be useful for traffic
      management and traffic modeling.

PMID- 29364935
TI  - Effects of Mindfulness-Based Stress Reduction on employees' mental health: A
      systematic review.
AB  - OBJECTIVES: The purpose of this exploratory study was to obtain greater insight
      into the effects of Mindfulness-Based Stress Reduction (MBSR) and Mindfulness
      Based Cognitive Therapy (MBCT) on the mental health of employees. METHODS: Using
      PsycINFO, PubMed, and CINAHL, we performed a systematic review in October 2015 of
      studies investigating the effects of MBSR and MBCT on various aspects of
      employees' mental health. Studies with a pre-post design (i.e. without a control
      group) were excluded. RESULTS: 24 articles were identified, describing 23
      studies: 22 on the effects of MBSR and 1 on the effects of MBSR in combination
      with some aspects of MBCT. Since no study focused exclusively on MBCT, its
      effects are not described in this systematic review. Of the 23 studies, 2 were of
      high methodological quality, 15 were of medium quality and 6 were of low quality.
      A meta-analysis was not performed due to the emergent and relatively uncharted
      nature of the topic of investigation, the exploratory character of this study,
      and the diversity of outcomes in the studies reviewed. Based on our analysis, the
      strongest outcomes were reduced levels of emotional exhaustion (a dimension of
      burnout), stress, psychological distress, depression, anxiety, and occupational
      stress. Improvements were found in terms of mindfulness, personal accomplishment
      (a dimension of burnout), (occupational) self-compassion, quality of sleep, and
      relaxation. CONCLUSION: The results of this systematic review suggest that MBSR
      may help to improve psychological functioning in employees.

PMID- 29364937
TI  - The impact of stillbirth on bereaved parents: A qualitative study.
AB  - PURPOSE: To explore the lived experiences and personal impact of stillbirth on
      bereaved parents. METHODS: Semi-structured in-depth interviews analysed by
      Interpretative Phenomenological Analysis (IPA) on a purposive sample of parents
      of twelve babies born following fetal death at a tertiary university maternity
      hospital in Ireland with a birth rate of c8,500 per annum and a stillbirth rate
      of 4.6/1000. RESULTS: Stillbirth had a profound and enduring impact on bereaved
      parents. Four superordinate themes relating to the human impact of stillbirth
      emerged from the data: maintaining hope, importance of the personhood of the
      baby, protective care and relationships (personal and professional). Bereaved
      parents recalled in vivid detail their experiences of care following diagnosis of
      stillbirth and their subsequent care. The time between diagnosis of a life
      limiting anomaly or stillbirth and delivery is highlighted as important for
      parents as they find meaning in their loss. CONCLUSIONS: The impact of stillbirth
      on bereaved parents is immense and how parents are cared for is recalled in
      precise detail as they revisit their experience. Building on existing literature,
      these data bring to light the depth of personal experience and impact of
      stillbirth for parents and provides medical professionals with valuable insights
      to inform their care of bereaved parents and the importance of clear and
      sensitive communication.

PMID- 29364938
TI  - Health-related quality of life inequalities by sexual orientation: Results from
      the Barcelona Health Interview Survey.
AB  - BACKGROUND: Studies on health-related quality of life (HRQoL) inequalities
      according to sexual orientation are scarce. The aim of this study was to assess
      HRQoL inequalities between lesbian, gay, and bisexual (LGB) people and
      heterosexuals in the 2011 Barcelona population, to describe the extent to which
      sociodemographic characteristics, health-related behaviors, and chronic
      conditions could explain such inequalities, and to understand if they are sexual
      orientation inequities. METHODS: In the 2011 Barcelona Health Interview Survey
      3277 adults answered the EQ-5D, which measures five dimensions of HRQoL
      summarized into a single utility index (1 = perfect health, 0 = death). To assess
      HRQoL differences by sexual orientation we constructed Tobit models for the EQ-5D
      index, and Poisson regression models for the EQ-5D dimensions. In both cases,
      nested models were constructed to assess the mediator role of selected variables.
      RESULTS: After adjusting by socio-demographic variables, the LGB group presented
      a significantly lower EQ-5D index than heterosexuals, and higher prevalence
      ratios of problems in physical EQ-5D dimensions among both genders: adjusted
      prevalence ratio (aPR) = 1.70 for mobility (p = 0.046) and 2.11 for usual
      activities (p = 0.019). Differences in mental dimensions were only observed among
      men: aPR = 3.15 for pain/discomfort (p = 0.003) and 2.49 for anxiety/depression
      (p = 0.030). All these differences by sexual orientation disappeared after adding
      chronic conditions and health-related behaviors in the models. CONCLUSION: The
      LGB population presented worse HRQoL than heterosexuals in the EQ-5D index and
      most dimensions. Chronic conditions, health-related behaviors and gender play a
      major role in explaining HRQoL differences by sexual orientation. These findings
      support the need of including sexual orientation into the global agenda of health
      inequities.

PMID- 29364940
TI  - Similarities and differences among half-marathon runners according to their
      performance level.
AB  - This study aimed to identify the similarities and differences among half-marathon
      runners in relation to their performance level. Forty-eight male runners were
      classified into 4 groups according to their performance level in a half-marathon
      (min): Group 1 (n = 11, < 70 min), Group 2 (n = 13, < 80 min), Group 3 (n = 13, <
      90 min), Group 4 (n = 11, < 105 min). In two separate sessions, training-related,
      anthropometric, physiological, foot strike pattern and spatio-temporal variables
      were recorded. Significant differences (p<0.05) between groups (ES = 0.55-3.16)
      and correlations with performance were obtained (r = 0.34-0.92) in training
      related (experience and running distance per week), anthropometric (mass, body
      mass index and sum of 6 skinfolds), physiological (VO2max, RCT and running
      economy), foot strike pattern and spatio-temporal variables (contact time, step
      rate and length). At standardized submaximal speeds (11, 13 and 15 km.h-1), no
      significant differences between groups were observed in step rate and length,
      neither in contact time when foot strike pattern was taken into account. In
      conclusion, apart from training-related, anthropometric and physiological
      variables, foot strike pattern and step length were the only biomechanical
      variables sensitive to half-marathon performance, which are essential to achieve
      high running speeds. However, when foot strike pattern and running speeds were
      controlled (submaximal test), the spatio-temporal variables were similar. This
      indicates that foot strike pattern and running speed are responsible for spatio
      temporal differences among runners of different performance level.

PMID- 29364939
TI  - Association between dietary protein intake and grip strength among adults aged 51
      years and over: What We Eat in America, National Health and Nutrition Examination
      Survey 2011-2014.
AB  - INTRODUCTION: Distributing daily protein intake evenly across meals (~25
      30g/meal) has been suggested to improve muscle mass. The aim of this research is
      to examine the association between grip strength, total protein intake and its
      distribution across day's meals in older adults. METHODS: Nationally
      representative dietary intake data of adults aged 51 years and older (n = 4,123)
      who participated in What We Eat in America, NHANES 2011-2014 were analyzed.
      Protein intake per day and per eating occasion (breakfast, lunch, dinner, and
      snack) were determined. Combined grip strength was calculated and expressed in
      kilograms. Grip strength of individuals consuming >=25g protein at 1 eating
      occasion was compared with those consuming same level of protein at 2 and 3 or
      more eating occasions. Grip strength of individuals in quartile 1 of daily
      protein intake was compared to those in the other quartiles. All associations
      were examined without and with adjustment for age, race/ethnicity, physical
      activity, health status, and smoking status. The comparison involving eating
      occasions and protein intake quartiles were further adjusted for daily protein
      intake and energy intake, respectively. RESULTS: Only 33% of men and 19% of women
      had protein intake of >=25g at 2 or more eating occasions. These individuals also
      had higher grip strength and daily protein intake. Grip strength was positively
      associated with consumption of >=25g protein at 2 eating occasions as compared to
      consumption of same level of protein at 1 eating occasion (p<0.05) in unadjusted
      model, but not when adjusted. Grip strength was positively associated with daily
      protein intake among women in quartiles 3 and 4 (p<0.05) of protein intake in
      both unadjusted and adjusted models compared to lowest protein intake. Among men,
      grip strength was associated with daily protein intake in quartiles 3 and 4
      (p<0.05) in the unadjusted model, but not when adjusted. CONCLUSION: In a
      nationally representative sample of older adults, consuming >=25g protein at 2 or
      more eating occasions was not associated with grip strength. However, higher
      daily protein intake was positively associated with grip strength in women.

PMID- 29364941
TI  - Prognostic value of presepsin in adult patients with sepsis: Systematic review
      and meta-analysis.
AB  - OBJECTIVE: Presepsin is a novel biomarker to diagnose sepsis but its prognostic
      value has not been comprehensively reviewed. We conducted this meta-analysis to
      evaluate the mortality prediction value of presepsin in sepsis. METHODS: We
      searched comprehensive electronic databases from PubMed, EMBASE, and Cochrane
      Library through September 2017 using the key words of ('presepsin' or 'sCD14-ST'
      or 'soluble CD14 subtype') and ('sepsis' or 'septic shock') and ('prognosis' or
      'prognostic value' or 'prognostic biomarker' or 'mortality'). We extracted the
      presepsin levels in survivors and non-survivors from each individual study and
      evaluated the standardized mean difference (SMD) using a web-based meta-analysis
      with the R statistical analysis program. RESULTS: A total of 10 studies and 1617
      patients were included. Presepsin levels in the first sampling (within 24 hours)
      were significantly lower among survivors as compared with non-survivors: the
      pooled SMD between survivors and non-survivors was 0.92 (95% CI: 0.62-1.22) in
      the random effects model (I2 = 79%, P< 0.01). In subgroups, divided by the sepsis
      severity or study site, pooled SMD was consistently noting higher presepsin
      levels in non-survivals (P< 0.05). CONCLUSION: This meta-analysis demonstrates
      some mortality prediction value in presepsin in patients with sepsis. Further
      studies are needed to define the optimal cut-off point to predict mortality in
      sepsis.

PMID- 29364942
TI  - Seed germination response to high temperature and water stress in three invasive
      Asteraceae weeds from Xishuangbanna, SW China.
AB  - Crassocephalum crepidioides, Conyza canadensis, and Ageratum conyzoides are alien
      annuals naturalized in China, which produce a large number of viable seeds every
      year. They widely grow in Xishuangbanna, becoming troublesome weeds that compete
      with crops for water and nutrients. As seed germination is among the most
      important life-stages which contribute to plant distribution and invasiveness,
      its adaptation to temperature and water stress were investigated in these three
      species. Results showed that: (1) These three species have wide temperature
      ranges to allow seed germination, i.e., high germination and seedling percentages
      were achieved between 15 degrees C and 30 degrees C, but germination was
      seriously inhibited at 35 degrees C; only A. conyzoides demonstrated relative
      preference for warmer temperatures with approximately 25% germination and
      seedling percentage at 35 degrees C; (2) light was a vital germination
      prerequisite for C. crepidioides and A. conyzoides, whereas most C. canadensis
      seeds germinated in full darkness; (3) Although all three species have good
      adaptation to bare ground habitat characterized by high temperatures and water
      stress, including their tolerance to soil surface temperatures of 70 degrees C in
      air-dried seeds, A. conyzoides seeds exhibited higher tolerance to both
      continuous and daily periodic high-temperature treatment at 40 degrees C, and to
      water restriction (e.g., ca. 65% seeds germinated to -0.8 MPa created by NaCl),
      which is consistent with their field behavior in Xishuangbanna. This study
      suggests that seed high-temperature tolerance contributes to the weed attributes
      of these three species, and that adaptation to local micro-habitats is a critical
      determinant for invasiveness of an alien plant.

PMID- 29364943
TI  - Area-level income inequality and oral health among Australian adults-A population
      based multilevel study.
AB  - BACKGROUND: A lack of evidence exists on the association between area-level
      income inequality and oral health within Australia. This study examined
      associations between area-level income inequality and oral health outcomes
      (inadequate dentition (<21 teeth) and poor self-rated oral health) among
      Australian adults. Variations in the association between area-level income
      inequality and oral health outcomes according to area-level mean income were also
      assessed. Finally, household-income gradients in oral health outcomes according
      to area-level income inequality were compared. METHODS: For the analyses, data on
      Australian dentate adults (n = 5,165 nested in 435 Local Government Areas (LGAs))
      was obtained from the National Dental Telephone Interview Survey-2013. Multilevel
      multivariable logistic regression models with random intercept and fixed slopes
      were fitted to test associations between area-level income inequality and oral
      health outcomes, examine variations in associations according to area-level mean
      income, and examine variations in household-income gradients in outcomes
      according to area-level income inequality. Covariates included age, sex, LGA
      level mean weekly household income, geographic remoteness and household income.
      RESULTS: LGA-level income inequality was not associated with poor self-rated oral
      health and inversely associated with inadequate dentition (OR: 0.64; 95% CI:
      0.48, 0.87) after adjusting for covariates. Inverse association between income
      inequality and inadequate dentition at the individual level was limited to LGAs
      within the highest tertile of mean weekly household income. Household income
      gradients in both outcomes showed poorer oral health at lower levels of household
      income. The household income gradients for inadequate dentition varied according
      to the LGA-level income inequality. CONCLUSION: Findings suggest that income
      inequality at the LGA-level in Australia is not positively associated with poorer
      oral health outcomes. Inverse association between income inequality and
      inadequate dentition is likely due to the contextual differences between
      Australia and other high-income countries.

PMID- 29364946
TI  - Correction: Specific and Evolving Resting-State Network Alterations in Post
      Concussion Syndrome Following Mild Traumatic Brain Injury.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0065470.].

PMID- 29364944
TI  - Associations between sexual habits, menstrual hygiene practices, demographics and
      the vaginal microbiome as revealed by Bayesian network analysis.
AB  - The vaginal microbiome plays an influential role in several disease states in
      reproductive age women, including bacterial vaginosis (BV). While demographic
      characteristics are associated with differences in vaginal microbiome community
      structure, little is known about the influence of sexual and hygiene habits.
      Furthermore, associations between the vaginal microbiome and risk symptoms of
      bacterial vaginosis have not been fully elucidated. Using Bayesian network (BN)
      analysis of 16S rRNA gene sequence results, demographic and extensive
      questionnaire data, we describe both novel and previously documented associations
      between habits of women and their vaginal microbiome. The BN analysis approach
      shows promise in uncovering complex associations between disparate data types.
      Our findings based on this approach support published associations between
      specific microbiome members (e.g., Eggerthella, Gardnerella, Dialister, Sneathia
      and Ruminococcaceae), the Nugent score (a BV diagnostic) and vaginal pH (a risk
      symptom of BV). Additionally, we found that several microbiome members were
      directly connected to other risk symptoms of BV (such as vaginal discharge, odor,
      itch, irritation, and yeast infection) including L. jensenii, Corynebacteria, and
      Proteobacteria. No direct connections were found between the Nugent Score and
      risk symptoms of BV other than pH, indicating that the Nugent Score may not be
      the most useful criteria for assessment of clinical BV. We also found that
      demographics (i.e., age, ethnicity, previous pregnancy) were associated with the
      presence/absence of specific vaginal microbes. The resulting BN revealed several
      as-yet undocumented associations between birth control usage, menstrual hygiene
      practices and specific microbiome members. Many of these complex relationships
      were not identified using common analytical methods, i.e., ordination and
      PERMANOVA. While these associations require confirmatory follow-up study, our
      findings strongly suggest that future studies of the vaginal microbiome and
      vaginal pathologies should include detailed surveys of participants' sanitary,
      sexual and birth control habits, as these can act as confounders in the
      relationship between the microbiome and disease. Although the BN approach is
      powerful in revealing complex associations within multidimensional datasets, the
      need in some cases to discretize the data for use in BN analysis can result in
      loss of information. Future research is required to alleviate such limitations in
      constructing BN networks. Large sample sizes are also required in order to allow
      for the incorporation of a large number of variables (nodes) into the BN,
      particularly when studying associations between metadata and the microbiome. We
      believe that this approach is of great value, complementing other methods, to
      further our understanding of complex associations characteristic of microbiome
      research.

PMID- 29364947
TI  - The Berkeley Dry Eye Flow Chart: A fast, functional screening instrument for
      contact lens-induced dryness.
AB  - PURPOSE: In this article, we introduce a novel flow chart-based screening tool
      for the categorization of contact lens-induced dryness (CLIDE) and its impact on
      daily visual activities: the Berkeley Dry Eye Flow Chart (DEFC). METHODS: One
      hundred thirty (130) experienced soft contact lens wearers discontinued lens wear
      for 24 hrs, passed a baseline screening and eye health examination, completed the
      Ocular Surface Disease Index (OSDI) then were dispensed fresh pairs of their
      habitual lenses. After 6 hrs of wear, subjects were administered a battery of
      symptom questionnaires, and underwent non-invasive tear breakup time (NITBUT)
      measurement, grading of distortion in reflected topographer mires, grading of
      lens surface wettability, and a fluorescein examination of the ocular surface.
      Subjects returned after at least 48 hrs and repeated all assessments after 6 hrs
      of wear of a second fresh pair of habitual lenses. RESULTS: The repeatability of
      the DEFC between visits was within 1%, and Limits of Agreement and Coefficient of
      Repeatability were comparable to those of the other CLIDE assessments. Higher
      DEFC score was significantly related to shorter pre-lens NITBUT, higher OSDI
      score, and higher Visual Analog Scale (VAS) ratings of average and end-of-day
      severity and frequency of dryness (all p < 0.001). For CLIDE as diagnosed based
      on DEFC score, the highest sensitivities and specificities were achieved by the
      OSDI and VAS ratings; pre-lens NITBUT exhibited good sensitivity but poor
      specificity. The optimum pre-lens NITBUT diagnostic threshold was found to be <=
      2.0 sec for debilitating CLIDE, and the OSDI threshold was >= 11.4. CONCLUSIONS:
      The DEFC provides a means of quickly categorizing CLIDE patients based on
      severity and frequency of symptoms, and on the degree to which symptoms impact
      daily life. The DEFC has several potential advantages as a CLIDE screening and
      monitoring tool, has good repeatability, and is significantly related to commonly
      employed clinical assessments for CLIDE.

PMID- 29364948
TI  - MRI reveals menstrually-related muscle edema that negatively affects athletic
      agility in young women.
AB  - CONTEXT: About 10% of Japanese female athletes are afflicted by menstrually
      related edema, mainly in the lower limbs, and, with few studies on this problem,
      the effect on performance remains unclear. OBJECTIVE: To quantitatively evaluate
      fluid retention in the calf in female students over their menstrual cycle using
      magnetic resonance imaging (MRI) and to determine the relationship of MRI changes
      and athletic performance. DESIGN: The menstrual cycle was divided into 5 phases:
      menstrual, follicular, ovulatory, early luteal, and late luteal with sampling
      done in either morning (AM) or afternoon (PM) sessions. At each phase, MRI of the
      calf (7:00-8:00, 14:00-16:00), body composition and hormones (7:00-8:00), and
      athletic performance (14:00-16:00) were evaluated. PARTICIPANTS: 13 adult healthy
      Japanese female students with eumenorrhea. RESULTS: Estradiol levels decreased
      significantly in the menstrual phase and the follicular phase compared to the
      early luteal phase (P = 0.001, P = 0.024 respectively). Menstrual phase estradiol
      levels were significantly lower compared to the ovulatory phase (P = 0.015), and
      the late luteal phase (P = 0.003). Progesterone levels decreased significantly in
      the menstrual phase and the follicular phase compared to the ovulatory phase (P =
      0.012, P = 0.009 respectively), the early luteal phase (both P = 0.007), and the
      late luteal phase (P = 0.028, P = 0.029 respectively), and it along with a
      significant decrease in the ovulatory phase compared to the early luteal phase (P
      = 0.010). AM T2 signals were significantly lower in the menstrual phase compared
      to the ovulatory phase (P = 0.043) but not other phases. PM T2 signals increased
      significantly in the menstrual phase compared to the follicular phase (P =
      0.003), ovulatory phase (P = 0.009), and the late luteal phase (P = 0.032), and
      the difference between the AM and PM values increased significantly in the
      menstrual phase compared to the other 4 phases (P<0.01). A negative correlation
      between fluid retention and agility was observed. CONCLUSION: In female students
      fluid retention during the menstrual phase could be a factor that influences
      athletic agility.

PMID- 29364949
TI  - Projected impacts of climate change on habitat availability for an endangered
      parakeet.
AB  - In tropical montane cloud forests, climate change can cause upslope shifts in the
      distribution ranges of species, leading to reductions in distributional range.
      Endemic species with small ranges are particularly vulnerable to such decreases
      in range size, as the population size may be reduced significantly. To ensure the
      survival of cloud forest species in the long term, it is crucial to quantify
      potential future shifts in their distribution ranges and the related changes in
      habitat availability in order to assure the long-term effectiveness of
      conservation measures. In this study, we assessed the influence of climate change
      on the availability of forested habitat for the endemic El Oro parakeet. We
      investigated the future range shift by modelling the climatic niche of the El Oro
      parakeets and projecting it to four different climate change scenarios. Depending
      on the intensity of climate change, the El Oro parakeets shift their range
      between 500 and 1700 m uphill by the year 2100. On average, the shift is
      accompanied by a reduction in range size to 15% and a reduction in forested
      habitat to only 10% of the original extent. Additionally, the connectivity
      between populations in different areas is decreasing in higher altitudes. To
      prevent a population decline due to habitat loss following an upslope range
      shift, it will be necessary to restore habitat across a large elevational span in
      order to allow for movement of El Oro parakeets into higher altitudes.

PMID- 29364950
TI  - The structure of FIV reverse transcriptase and its implications for non
      nucleoside inhibitor resistance.
AB  - Reverse transcriptase (RT) is the target for the majority of anti-HIV-1 drugs. As
      with all anti-AIDS treatments, continued success of RT inhibitors is persistently
      disrupted by the occurrence of resistance mutations. To explore latent resistance
      mechanisms potentially accessible to therapeutically challenged HIV-1 viruses, we
      examined RT from the related feline immunodeficiency virus (FIV). FIV closely
      parallels HIV-1 in its replication and pathogenicity, however, is resistant to
      all non-nucleoside inhibitors (NNRTI). The intrinsic resistance of FIV RT is
      particularly interesting since FIV harbors the Y181 and Y188 sensitivity residues
      absent in both HIV-2 and SIV. Unlike RT from HIV-2 or SIV, previous efforts have
      failed to make FIV RT susceptible to NNRTIs concluding that the structure or
      flexibility of the feline enzyme must be profoundly different. We report the
      first crystal structure of FIV RT and, being the first structure of an RT from a
      non-primate lentivirus, enrich the structural and species repertoires available
      for RT. The structure demonstrates that while the NNRTI binding pocket is
      conserved, minor subtleties at the entryway can render the FIV RT pocket more
      restricted and unfavorable for effective NNRTI binding. Measuring NNRTI binding
      affinity to FIV RT shows that the "closed" pocket configuration inhibits NNRTI
      binding. Mutating the loop residues rimming the entryway of FIV RT pocket allows
      for NNRTI binding, however, it does not confer sensitivity to these inhibitors.
      This reveals a further layer of resistance caused by inherent FIV RT variances
      that could have enhanced the dissociation of bound inhibitors, or, perhaps,
      modulated protein plasticity to overcome inhibitory effects of bound NNRTIs. The
      more "closed" conformation of FIV RT pocket can provide a template for the
      development of innovative drugs that could unlock the constrained pocket, and the
      resilient mutant version of the enzyme can offer a fresh model for the study of
      NNRTI-resistance mechanisms overlooked in HIV-1.

PMID- 29364951
TI  - Seasonal differences of corticosterone metabolite concentrations and parasite
      burden in northern bald ibis (Geronticus eremita): The role of affiliative
      interactions.
AB  - The reproductive season is energetically costly as revealed by elevated
      glucocorticoid concentrations, constrained immune functions and an increased risk
      of infections. Social allies and affiliative interactions may buffer
      physiological stress responses and thereby alleviate associated effects. In the
      present study, we investigated the seasonal differences of immune reactive
      corticosterone metabolite concentrations, endoparasite burden (nematode eggs and
      coccidian oocysts) and affiliative interactions in northern bald ibis (Geronticus
      eremita), a critically endangered bird. In total, 43 individually marked focal
      animals from a free-ranging colony were investigated. The analyses included a
      description of initiated and received affiliative interactions, pair bond status
      as well as seasonal patterns of hormone and endoparasite levels. During the
      reproductive season, droppings contained parasite eggs more often and
      corticosterone metabolite levels were higher as compared to the period after
      reproduction. The excretion rate of endoparasite products was lower in paired
      individuals than in unpaired ones, but paired animals exhibited higher
      corticosterone metabolite concentrations than unpaired individuals. Furthermore,
      paired individuals initiated affiliative behaviour more frequently than unpaired
      ones. This suggests that the reproductive season influences the excretion
      patterns of endoparasite products and corticosterone metabolites and that
      affiliative interactions between pair partners may positively affect endoparasite
      burden during periods of elevated glucocorticoid levels. Being embedded in a pair
      bond may have a positive impact on individual immune system and parasite
      resistance.

PMID- 29364952
TI  - Association between socioeconomic status and cerebral palsy.
AB  - BACKGROUND: The present study investigated the annual prevalence of cerebral
      palsy (CP) among children aged <7 years in Taiwan and the association between
      socioeconomic status and CP prevalence. METHODS: Data from the Taiwan National
      Health Insurance Research Database for the 2002-2008 period were used in this
      population-based study. Severe and total CP were defined according to
      catastrophic illness certificate and medical claim records, respectively. The
      annual CP prevalence was calculated as the number of children with CP among all
      children aged <7 years. RESULTS: From 2002 to 2008, the annual prevalence of
      total and severe CP ranged from 1.9 to 2.8 and from 1.1 to 1.4 per 1000 children,
      respectively. Boys were 30% more likely to have CP than girls [adjusted relative
      risk (RR) and 95% confidence interval (CI) ranged from 1.3 (1.2-1.4) to 1.4 (1.2
      1.5)]. Low family income was associated with a higher CP prevalence [adjusted RR
      (95% CI) ranged from 5.1 (4.2-6.2) to 6.4 (5.4-7.6)]. The prevalence of CP in
      rural area was higher than that in urban or suburban areas. The mortality rate of
      severe CP ranged from 12.2-22.7 per 1000 children within the 7 years study
      period. CONCLUSIONS: The prevalence of CP in Taiwan is similar to that in Western
      countries. A higher prevalence of CP is associated with male sex, low income, and
      rural residential location. Our findings provide insights into CP epidemiology
      among the Chinese population.

PMID- 29364953
TI  - Can data from disparate long-term fish monitoring programs be used to increase
      our understanding of regional and continental trends in large river assemblages?
AB  - Understanding trends in the diverse resources provided by large rivers will help
      balance tradeoffs among stakeholders and inform strategies to mitigate the
      effects of landscape scale stressors such as climate change and invasive species.
      Absent a cohesive coordinated effort to assess trends in important large river
      resources, a logical starting point is to assess our ability to draw inferences
      from existing efforts. In this paper, we use a common analytical framework to
      analyze data from five disparate fish monitoring programs to better understand
      the nature of spatial and temporal trends in large river fish assemblages. We
      evaluated data from programs that monitor fishes in the Colorado, Columbia,
      Illinois, Mississippi, and Tallapoosa rivers using non-metric dimensional scaling
      ordinations and associated tests to evaluate trends in fish assemblage structure
      and native fish biodiversity. Our results indicate that fish assemblages
      exhibited significant spatial and temporal trends in all five of the rivers. We
      also document native species diversity trends that were variable within and
      between rivers and generally more evident in rivers with higher species richness
      and programs of longer duration. We discuss shared and basin-specific landscape
      level stressors. Having a basic understanding of the nature and extent of trends
      in fish assemblages is a necessary first step towards understanding factors
      affecting biodiversity and fisheries in large rivers.

PMID- 29364954
TI  - Correction: Hepatic Lipid Accumulation Alters Global Histone H3 Lysine 9 and 4
      Trimethylation in the Peroxisome Proliferator-Activated Receptor Alpha Network.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0044345.].

PMID- 29364955
TI  - Removal of stabilizers from human serum albumin by adsorbents and dialysis used
      in blood purification.
AB  - INTRODUCTION: Human serum albumin (HSA) is a monomeric multi-domain protein that
      possesses an extraordinary binding capacity. It plays an important role in
      storing and transporting endogenous substances, metabolites, and drugs throughout
      the human circulatory system. Clinically, HSA is used to treat a variety of
      diseases such as hypovolemia, shock, burns, hemorrhage, and trauma in critically
      ill patients. Pharmaceutical-grade HSA contains the stabilizers sodium caprylate
      and N-acetyltryptophanate to protect the protein from oxidative stress and to
      stabilize it for heat treatment which is applied for virus inactivation. MATERIAL
      AND METHODS: The aim of this study was to determine if the two stabilizers can be
      depleted by adsorbent techniques. Several, adsorbents, some of them are in
      clinical use, were tested in batch and in a dynamic setup for their ability to
      remove the stabilizers. Furthermore, the removal of the stabilizers was tested
      using a pediatric high flux dialyzer. RESULTS: The outcome of this study shows
      that activated charcoal based adsorbents are more effective in removal of N
      acetylthryptophanate, whereas polystyrene based adsorbents are better for the
      removal of caprylate from HSA solutions. An adsorbent cartridge which contains a
      mix of activated charcoal and polystyrene based material could be used to remove
      both stabilizers effectively. After 4 hours treatment with a high flux dialyzer,
      N-acetyltryptophanate was totally removed whereas 20% of caprylate remained in
      the HSA solution.

PMID- 29364956
TI  - The long noncoding RNA lncR492 inhibits neural differentiation of murine
      embryonic stem cells.
AB  - RNA interference (RNAi) screens have been shown to be valuable to study embryonic
      stem cell (ESC) self-renewal and they have been successfully applied to identify
      coding as well as noncoding genes required for maintaining pluripotency. Here, we
      used an RNAi library targeting >640 long noncoding RNAs (lncRNA) to probe for
      their role in early cell differentiation. Utilizing a Sox1-GFP ESC reporter cell
      line, we identified the lncRNA lncR492 as lineage-specific inhibitor of
      neuroectodermal differentiation. Molecular characterization showed that lncR492
      interacts with the mRNA binding protein HuR and facilitates its inhibitory
      function by activation of Wnt signaling. Thus, lncRNAs modulate the fate decision
      of pluripotent stem cells.

PMID- 29364957
TI  - Impact of gender, organized athletics, and video gaming on driving skills in
      novice drivers.
AB  - Given that novice drivers tend to be young, and teenagers and young adult drivers
      are involved in the greatest number of accidents, it is important that we
      understand what factors impact the driving skills of this population of drivers.
      The primary aim of the present study was to understand the impact of gender,
      organized athletics, and video gaming on driving skills of novice drivers under
      real-world driving conditions. Novice driving students having less than five
      hours driving experience previous to a normal driving lesson were evaluated on
      their self-confidence (self-reported) prior to the lesson and driving skill
      evaluated by their instructor during the course of the lesson. Information was
      collected about gender, age, whether or not the students were involved in
      organized athletics, and the extent of their video game playing. There was no
      impact of gender or extent of video game playing on driving skills. Females were
      significantly less self-confident with driving than males, but this did not
      translate to gender differences in driving skills. Being involved in organized
      athletics-either currently or in the past-significantly enhanced driving skills
      in both females and males. Finally, novice drivers' age was negatively correlated
      with driving skills. That is, younger novice drivers (especially males) had
      better driving skills than older novice drivers. This is counter to popular
      belief that young drivers lack technical driving skills because they have less
      experience behind the wheel. Based on the results of the current study, we
      hypothesize that the relatively high accident rate of younger drivers (especially
      male drivers) is most likely due to inattention to safety considerations rather
      than lack of technical driving ability.

PMID- 29364958
TI  - Comparisons of oncological outcomes and perioperative complications between
      laparoscopic and open radical nephrectomies in patients with clinical T2 renal
      cell carcinoma (>=7cm).
AB  - PURPOSE: Although minimal invasive techniques have been widely accepted in
      contemporary urology, the perioperative outcomes of laparoscopy in patients with
      clinical T2 renal cell carcinoma (RCC) have not been clearly evaluated. We aimed
      to compare the outcomes of laparoscopic radical nephrectomy (LRN) with those of
      open radical nephrectomy (ORN) in patients with clinical T2 RCC. METHODS: We
      retrospectively analyzed the data of 835 patients who underwent radical
      nephrectomy for localized clinical T2 RCC (>=7 cm). The survival rates and
      postoperative complications were compared between the LRN and ORN groups.
      Multivariate Cox regression tests were performed to identify the independent
      predictors of each survival outcome. RESULTS: There were 578 (69.2%) subjects in
      ORN group and 257 (30.8%) in LRN group, respectively. The LRN group showed a
      significant male predominance (p = 0.013), higher pathological stage (p = 0.02),
      and higher cellular grade (p = 0.010) compared with the ORN group. No significant
      differences in progression-free (p = 0.070), cancer-specific (p = 0.472), or
      overall survival (p = 0.249) were found between the two groups. In the
      multivariate analysis, the type of surgery did not show any significant
      associations with all three survival outcomes (all p > 0.2). Furthermore, there
      was no significant difference in postoperative complication rate between the two
      groups (p = 0.595). In the subgroup analysis according to tumor histology, no
      significant relationships were observed between survival outcome and surgery
      type. CONCLUSION: The LRN and ORN groups showed similar oncological outcomes in
      patients with clinical T2 RCC. Early postoperative complications were also
      comparable between LRN and ORN.

PMID- 29364961
TI  - Correction: A Functional Screen Identifies Specific MicroRNAs Capable of
      Inhibiting Human Melanoma Cell Viability.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0043569.].

PMID- 29364960
TI  - Empiric tuberculosis treatment in South African primary health care facilities -
      for whom, where, when and why: Implications for the development of tuberculosis
      diagnostic tests.
AB  - BACKGROUND: The extent and circumstances under which empiric tuberculosis (TB)
      treatment (treatment without microbiological confirmation at treatment
      initiation) is administered in primary health care settings in South Africa are
      not well described. METHODS: We used data from a pragmatic evaluation of Xpert
      MTB/RIF in which persons undergoing TB investigations by PHC nurses were followed
      for six months. Following Xpert or smear-microscopy at enrolment, investigations
      for tuberculosis were undertaken at the discretion of health care workers. We
      identified persons whose TB treatment was initiated empirically (no
      microbiological confirmation at time of treatment initiation at a primary health
      care facility) and describe pathways to treatment initiation. RESULTS: Of 4665
      evaluable participants, 541 persons were initiated on treatment of whom 167 (31%)
      had negative sputum tests at enrolment. Amongst these 167, the median number of
      participant visits to health care providers prior to treatment initiation was 3
      (interquartile range [IQR] 2-4). Chest radiography, sputum culture or hospital
      referral was done in 106/167 (63%). Reasons for TB treatment start were: 1)
      empiric (n = 82, 49%); 2) a positive laboratory test (n = 49, 29%); 3) referral
      and treatment start at a higher level of care (n = 28, 17%); and 4)
      indeterminable (n = 8, 5%). Empiric treatment accounted for 15% (82/541) of all
      TB treatment initiations and 1.7% (82/4665) of all persons undergoing TB
      investigations. Chest radiography findings compatible with TB (63/82 [77%]) were
      the basis for treatment initiation amongst the majority of empirically treated
      participants. Microbiological confirmation of TB was subsequently obtained for
      11/82 (13%) empirically-treated participants. Median time to empiric treatment
      start was 3.9 weeks (IQR 1.4-11 weeks) after enrolment. CONCLUSION: Uncommon
      prescription of empiric TB treatment with reliance on chest radiography in a
      nurse-managed programme underscores the need for highly sensitive TB diagnostics
      suitable for point-of-care, and strong health systems to support TB diagnosis in
      this setting.

PMID- 29364959
TI  - The influence of racism on cigarette smoking: Longitudinal study of young people
      in a British multiethnic cohort.
AB  - INTRODUCTION: Studies, predominantly from the US, suggest that positive
      parenting, social support, academic achievement, and ethnic identity may buffer
      the impact of racism on health behaviours, including smoking, but little is known
      about how such effects might operate for ethnically diverse young people in the
      United Kingdom. We use the Determinants of young Adult Social well-being and
      Health (DASH), the largest UK longitudinal study of ethnically diverse young
      people, to address the following questions: a) Is racism associated with smoking?
      b) Does the relationship between racism and smoking vary by gender and by
      ethnicity? (c) Do religious involvement, parenting style and relationship with
      parents modify any observed relationship? and d) What are the qualitative
      experiences of racism and how might family or religion buffer the impact?
      METHODS: The cohort was recruited from 51 London schools. 6643 were seen at 11
      13y and 4785 seen again at 14-16y. 665 participated in pilot follow-up at 21-23y,
      42 in qualitative interviews. Self-report questionnaires included lifestyles,
      socio-economic and psychosocial factors. Mixed-effect models examined the
      associations between racism and smoking. RESULTS: Smoking prevalence increased
      from adolescence to age 21-23y, although ethnic minorities remained less likely
      to smoke. Racism was an independent longitudinal correlate of ever smoking
      throughout adolescence (odds ratio 1.77, 95% Confidence Interval 1.45-2.17) and
      from early adolescence to early 20s (1.90, 95% CI 1.25-2.90). Smoking initiation
      in late adolescence was associated with cumulative exposure to racism (1.77, 95%
      CI 1.23-2.54). Parent-child relationships and place of worship attendance were
      independent longitudinal correlates that were protective of smoking. Qualitative
      narratives explored how parenting, religion and cultural identity buffered the
      adverse impact of racism. CONCLUSIONS: Racism was associated with smoking
      behaviour from early adolescence to early adulthood, regardless of gender,
      ethnicity or socio-economic circumstances adding to evidence of the need to
      consider racism as an important social determinant of health across the life
      course.

PMID- 29364962
TI  - A network approach to decentralized coordination of energy production-consumption
      grids.
AB  - Energy grids are facing a relatively new paradigm consisting in the formation of
      local distributed energy sources and loads that can operate in parallel
      independently from the main power grid (usually called microgrids). One of the
      main challenges in microgrid-like networks management is that of self-adapting to
      the production and demands in a decentralized coordinated way. Here, we propose a
      stylized model that allows to analytically predict the coordination of the
      elements in the network, depending on the network topology. Surprisingly, almost
      global coordination is attained when users interact locally, with a small
      neighborhood, instead of the obvious but more costly all-to-all coordination. We
      compute analytically the optimal value of coordinated users in random homogeneous
      networks. The methodology proposed opens a new way of confronting the analysis of
      energy demand-side management in networked systems.

PMID- 29364964
TI  - Correction: Properties and Molecular Determinants of the Natural Flavone Acacetin
      for Blocking hKv4.3 Channels.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0057864.].

PMID- 29364963
TI  - Association of usual sleep quality and glycemic control in type 2 diabetes in
      Japanese: A cross sectional study. Sleep and Food Registry in Kanagawa (SOREKA).
AB  - OBJECTIVES: Excessively short and long sleep durations are associated with type 2
      diabetes, but there is limited information about the association between sleep
      quality and diabetes. Accordingly, the present study was performed to investigate
      this relationship. MATERIALS AND METHODS: The subjects were 3249 patients with
      type 2 diabetes aged 20 years or older. Sleep quality was assessed by using the
      Pittsburgh Sleep Quality Index (PSQI). A higher global PSQI score indicates worse
      sleep quality, and a global PSQI score >5 differentiates poor sleepers from good
      sleepers. RESULTS: The mean global PSQI score was 5.94 +/- 3.33, and 47.6% of the
      patients had a score of 6 or higher. Regarding the components of the PSQI, the
      score was highest for sleep duration, followed by subjective sleep quality and
      then sleep latency in decreasing order. When the patients were assigned to HbA1c
      quartiles (<= 6.5%, 6.6-7.0%, 7.1-7.8%, and >= 7.9%), the top quartile had a
      significantly higher global PSQI score than the other quartiles. The top HbA1c
      quartile had a sleep duration of only 6.23 +/- 1.42 hours, which was
      significantly shorter than in the other quartiles. Also, sleep latency was 25.3
      +/- 31.8 minutes in the top quartile, which was significantly longer (by
      approximately 20 minutes) than in the other quartiles. When analysis was
      performed with adjustment for age, gender, BMI, smoking, and other confounders,
      the global PSQI score was still significantly higher and sleep duration was
      shorter in the top HbA1c quartile (HbA1c >= 7.9%). CONCLUSIONS: Japanese patients
      with type 2 diabetes were found to have poor subjective sleep quality
      independently of potential confounders, especially those with inadequate glycemic
      control. Impairment of sleep quality was associated with both increased sleep
      latency and a shorter duration of sleep.

PMID- 29364965
TI  - Correction: Comparison of the Predicted Population Coverage of Tuberculosis
      Vaccine Candidates Ag85B-ESAT-6, Ag85B-TB10.4, and Mtb72f via a Bioinformatics
      Approach.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0040882.].

PMID- 29364967
TI  - Correction: Validity of U.S. Nutritional Surveillance: National Health and
      Nutrition Examination Survey Caloric Energy Intake Data, 1971-2010.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0076632.].

PMID- 29364966
TI  - Novel anti-cancer drug COTI-2 synergizes with therapeutic agents and does not
      induce resistance or exhibit cross-resistance in human cancer cell lines.
AB  - Emerging drug-resistance and drug-associated toxicities are two major factors
      limiting successful cancer therapy. Combinations of chemotherapeutic drugs have
      been used in the clinic to improve patient outcome. However, cancer cells can
      acquire resistance to drugs, alone or in combination. Resistant tumors can also
      exhibit cross-resistance to other chemotherapeutic agents, resulting in sub
      optimal treatment and/or treatment failure. Therefore, developing novel oncology
      drugs that induce no or little acquired resistance and with a favorable safety
      profile is essential. We show here that combining COTI-2, a novel clinical stage
      agent, with multiple chemotherapeutic and targeted agents enhances the activity
      of these drugs in vitro and in vivo. Importantly, no overt toxicity was observed
      in the combination treatment groups in vivo. Furthermore, unlike the tested
      chemotherapeutic drugs, cancer cells did not develop resistance to COTI-2.
      Finally, some chemo-resistant tumor cell lines only showed mild cross-resistance
      to COTI-2 while most remained sensitive to it.

PMID- 29364968
TI  - Dental disease and dietary isotopes of individuals from St Gertrude Church
      cemetery, Riga, Latvia.
AB  - This research explores oral health indicators and stable carbon and nitrogen
      isotope data to explore diet, and differences in diet, between people buried in
      the four different contexts of the St Gertrude Church cemetery (15th- 17th
      centuries AD): the general cemetery, two mass graves, and a collective mass
      burial pit within the general cemetery. The main aim is to assess whether people
      buried in the mass graves were rural immigrants, or if they were more likely to
      be the victims of plague (or another epidemic) who lived in Riga and its suburbs.
      The data produced (from dental disease assessments and isotope analyses) were
      compared within, as well as between, the contexts. Most differences emerged when
      comparing the prevalence rates of dental diseases and other oral health
      indicators in males and females between the contexts, while isotope analysis
      revealed more individual, rather than context-specific, differences. The data
      suggested that the populations buried in the mass graves were different from
      those buried in the general cemetery, and support the theory that rural
      immigrants were buried in both mass graves. Significant differences were observed
      in some aspects of the data between the mass graves, however, possibly indicating
      that the people buried in them do not represent the same community.

PMID- 29364969
TI  - Contribution of oxidative stress and growth factor receptor transactivation in
      natriuretic peptide receptor C-mediated attenuation of hyperproliferation of
      vascular smooth muscle cells from SHR.
AB  - Earlier studies have shown the implication of growth factor receptor activation
      in angiotensin II (Ang II)-induced hyperproliferation of aortic VSMC as well as
      in hyperproliferation of VSMC from spontaneously hypertensive rats (SHR). We
      previously showed that NPR-C specific agonist C-ANP4-23 attenuates the
      hyperproliferation of VSMC from SHR through the inhibition of MAP kinase, Gialpha
      protein signaling and overexpression of cell cycle proteins. The aim of the
      present study was to investigate if C-ANP4-23- mediated attenuation of
      hyperproliferation of VSMC from SHR also involves growth factor receptor
      activation and upstream signaling molecules. For this study, C-ANP 4-23 (10
      nmole/kg body weight) was injected intraperitoneally into 2 week-old
      prehypertensive SHR and Wistar Kyoto (WKY) rats twice per week for 6 weeks. The
      blood pressure in SHR was significantly attenuated by C-ANP4-23 treatment. In
      addition, C-ANP4-23 treatment also attenuated the hyperproliferation of VSMC from
      SHR as well as the enhanced phosphorylation of EGF-R, PDGF-R, IGF-R and c-Src.
      Furthermore, the enhanced levels of superoxide anion, NADPH oxidase activity, and
      enhanced expression of Nox4,Nox1,Nox2 and P47phox in SHR compared to WKY rats was
      also significantly attenuated by C-ANP4-23 treatment. In addition, N-acetyl
      cysteine (NAC), a scavenger of O2-, inhibitors of growth factor receptors and of
      c-Src, all inhibited the overexpression of cell cycle proteins cyclin D1 and cdk4
      in VSMC from SHR. These results suggest that in vivo treatment of SHR with C-ANP4
      23 inhibits the enhanced oxidative stress, c-Src and EGF-R, PDGF-R, IGF-R
      activation which through the inhibition of overexpression of cell cycle proteins
      result in the attenuation of hyperproliferation of VSMC.

PMID- 29364970
TI  - Correction: Global computational mutagenesis provides a critical stability
      framework in protein structures.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189064.].

PMID- 29364971
TI  - Correction: Partial Agonism of Taurine at Gamma-Containing Native and Recombinant
      GABAA Receptors.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0061733.].

PMID- 29364972
TI  - Socioeconomic differences among community-dwelling diabetic adults screened for
      diabetic retinopathy and nephropathy: The 2015 Korean Community Health Survey.
AB  - We investigated the association between socioeconomic status (SES) and screening
      for diabetic retinopathy (DR) and diabetic nephropathy (DN) in community-dwelling
      diabetics. We analyzed data from 22,134 people with diabetes aged >=19 years at
      the time of the nationwide 2015 Korean Community Health Survey. Multiple logistic
      regression analysis was used to explore the relationship between SES and
      screening for DR and DN both before and after adjustment for health behaviors,
      comorbidities, and educational level. Of all diabetic subjects, 33.9% and 38.1%
      underwent DR and DN screening, respectively. In the fully adjusted model, the
      extent of the DR and DN screening trended significantly lower as the educational
      level fell. Monthly household income was positively associated with DR screening,
      but a lower odds ratio (OR) for DN screening was evident only when the lowest and
      highest income groups were compared. Compared with managers/professionals,
      agricultural/forestry/fishery workers (OR 0.81, 95% confidence interval [CI] 0.69
      0.96) and mechanical/manual laborers (OR 0.83, 95% CI 0.71-0.97) had lower ORs
      for DN screening. Residents in rural (compared with urban) areas and
      widows/widowers (compared with members of couples) were significantly less likely
      to undergo screening for DR and DN. Similar findings were obtained when the
      analysis was limited to those who had been educated about diabetes. In
      conclusion, socioeconomic inequalities were evident in terms of screening for DR
      and DN in community-dwelling Korean diabetics, regardless of whether they had
      reported receiving diabetes education. Tailored public health policies (and
      societal attention) are required to aid the socioeconomically disadvantaged.

PMID- 29364973
TI  - Correction: Effet of Combined Nitrogen Dioxide and Carbon Nanoparticle Exposure
      on Lung Function During Ovalbumin Sensitization in Brown Norway Rat.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0045687.].

PMID- 29364974
TI  - Correction: Exposure of bighorn sheep to domestic goats colonized with Mycoplasma
      ovipneumoniae induces sub-lethal pneumonia.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178707.].

PMID- 29364975
TI  - Correction: Spatial Analysis of Soil Organic Carbon in Zhifanggou Catchment of
      the Loess Plateau.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0083061.].

PMID- 29364976
TI  - Correction: Gene Regulatory Networks Controlling Hematopoietic Progenitor Niche
      Cell Production and Differentiation in the Drosophila Lymph Gland.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0041604.].

PMID- 29364977
TI  - Identification of microRNA that represses IRS-1 expression in liver.
AB  - MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally
      regulate gene expression and have been shown to participate in almost every
      cellular process. Several miRNAs have recently been implicated in glucose
      metabolism, but the roles of miRNAs in insulin-resistant conditions, such as
      obesity or type 2 diabetes, are largely unknown. Herein, we focused on miR-222,
      the expression of which was increased in the livers of high fat/high sucrose diet
      fed mice injected with gold thioglucose (G+HFHSD). Overexpression of miR-222 in
      primary mouse hepatocytes attenuated Akt phosphorylation induced by insulin,
      indicating that miR-222 negatively regulates insulin signaling. As per in silico
      analysis, miR-222 potentially binds to the 3' untranslated region (3' UTR) of the
      IRS-1 gene, a key insulin signaling molecule. In fact, IRS-1 protein expression
      was decreased in the livers of G+HFHSD-fed mice. We further confirmed a direct
      interaction between miR-222 and the 3' UTR of IRS-1 via luciferase assays. Our
      findings suggest that up-regulation of miR-222 followed by reduction in IRS-1
      expression may be a viable mechanism of insulin resistance in the liver.

PMID- 29364980
TI  - Correction: Linear Decay of Retrotransposon Antisense Bias across Genes Is
      Contingent upon Tissue Specificity.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0079402.].

PMID- 29364979
TI  - Navigating the risks of prevention of mother to child transmission (PMTCT) of HIV
      services in Kibera, Kenya: Barriers to engaging and remaining in care.
AB  - Within the first year of implementation, 43% of women who tested HIV positive at
      their first antenatal care visit were no longer retained and being followed in
      the free prevention of mother to child transmission (PMTCT) of HIV program
      offered by the Kenyan Ministry of Health and Medecins Sans Frontieres in the
      informal settlement of Kibera, Nairobi. This study aimed to explore barriers to
      enrolling and remaining engaged in PMTCT services throughout the pregnancy and
      postpartum periods. Qualitative data from 31 focus group discussions and 35 in
      depth interviews across six stakeholder groups that included women, men, and
      PMTCT service providers were analyzed. Using an inductive exploratory approach,
      four researchers coded the data and identified key themes. Five themes emerged
      from the data that may influence attrition from PMTCT service in this setting: 1)
      HIV in the context of Kibera, 2) knowledge of HIV status, 3) knowledge of PMTCT,
      4) disclosure of HIV status, and 5) male partner support for PMTCT services. A
      new HIV diagnosis during pregnancy immediately triggered an ongoing risk
      assessment of perceived hazards in the home, community, and clinic environments
      that could occur as a result of female participation in PMTCT services. Male
      partners were a major influence in this risk assessment, but were generally
      unaware of PMTCT services. To preserve relationships with male partners, meet
      community expectations of womanhood, and maintain confidentiality while following
      recommendations of healthcare providers, women had to continuously weigh the
      risks and benefits of PMTCT services and interventions. Community-based HIV
      testing and PMTCT education, male involvement in antenatal care, and counseling
      customized to assist each woman in her own unique risk assessment, may improve
      uptake of and retention in care and optimize the HIV prevention benefit of PMTCT
      interventions.

PMID- 29364978
TI  - Physical multimorbidity and loneliness: A population-based study.
AB  - Multimorbidity has been linked to a variety of negative outcomes although as yet,
      there has been little research on its association with loneliness. This study
      examined the association between physical multimorbidity (>= 2 physical diseases)
      and loneliness in the general population and its potential mediators. Data came
      from the Adult Psychiatric Morbidity Survey 2007 (N = 7403, aged >=16 years).
      Information was obtained on 20 doctor diagnosed physical conditions that were
      present in the previous year. An item from the Social Functioning Questionnaire
      (SFQ) was used to obtain information on loneliness. Multivariable logistic
      regression analysis was used to examine associations. An increasing number of
      physical diseases was associated with higher odds for loneliness. Compared to no
      physical diseases, the odds ratio (OR) (95% confidence interval: CI) for
      loneliness increased from 1.34 (1.13-1.59) to 2.82 (2.11-3.78) between one and
      >=5 physical diseases. This association was particularly strong in the youngest
      age group (i.e. 16-44 years). The loneliness-physical multimorbidity association
      was significantly mediated by stressful life events (% mediated 11.1%-30.5%),
      anxiety (30.2%), and depression (15.4%). Physical multimorbidity is associated
      with increased odds for loneliness. Prospective research is now needed to further
      elucidate this association and the factors that underlie it.

PMID- 29364981
TI  - Conditional mutagenesis in vivo reveals cell type- and infection stage-specific
      requirements for LANA in chronic MHV68 infection.
AB  - Gammaherpesvirus (GHV) pathogenesis is a complex process that involves productive
      viral replication, dissemination to tissues that harbor lifelong latent
      infection, and reactivation from latency back into a productive replication
      cycle. Traditional loss-of-function mutagenesis approaches in mice using murine
      gammaherpesvirus 68 (MHV68), a model that allows for examination of GHV
      pathogenesis in vivo, have been invaluable for defining requirements for specific
      viral gene products in GHV infection. But these approaches are insufficient to
      fully reveal how viral gene products contribute when the encoded protein
      facilitates multiple processes in the infectious cycle and when these functions
      vary over time and from one host tissue to another. To address this complexity,
      we developed an MHV68 genetic platform that enables cell-type-specific and
      inducible viral gene deletion in vivo. We employed this system to re-evaluate
      functions of the MHV68 latency-associated nuclear antigen (mLANA), a protein with
      roles in both viral replication and latency. Cre-mediated deletion in mice of
      loxP-flanked ORF73 demonstrated the necessity of mLANA in B cells for MHV68
      latency establishment. Impaired latency during the transition from draining lymph
      nodes to blood following mLANA deletion also was observed, supporting the
      hypothesis that B cells are a major conduit for viral dissemination. Ablation of
      mLANA in infected germinal center (GC) B cells severely impaired viral latency,
      indicating the importance of viral passage through the GC for latency
      establishment. Finally, induced ablation of mLANA during latency resulted in
      complete loss of affected viral genomes, indicating that mLANA is critically
      important for maintenance of viral genomes during stable latency. Collectively,
      these experiments provide new insights into LANA homolog functions in GHV
      colonization of the host and highlight the potential of a new MHV68 genetic
      platform to foster a more complete understanding of viral gene functions at
      discrete stages of GHV pathogenesis.

PMID- 29364982
TI  - Correction: In Silico Study on Binding Specificity of Gonadotropins and Their
      Receptors: Design of a Novel and Selective Peptidomimetic for Human Follicle
      Stimulating Hormone Receptor.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0064475.].

PMID- 29364983
TI  - Correction: Identification of a Predicted Trimeric Autotransporter Adhesin
      Required for Biofilm Formation of Burkholderia pseudomallei.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0079461.].

PMID- 29364984
TI  - Correction: Uniparental Markers of Contemporary Italian Population Reveals
      Details on Its Pre-Roman Heritage.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0050794.].

PMID- 29364986
TI  - Investigation on size tolerance of pore defect of girth weld pipe.
AB  - Welding quality control is an important parameter for safe operation of oil and
      gas pipes, especially for high-strength steel pipes. Size control of welding
      defect is a bottleneck problem for current pipe construction. As a key part of
      construction procedure for butt-welding of pipes, pore defects in girth weld is
      difficult to ignore. A three-dimensional non-linear finite element numerical
      model is established to study applicability of size control indices based on
      groove shape and softening phenomenon of material in heat-affected zone of
      practical pipe girth weld. Taking design criteria of pipe as the basis, basic
      tensile, extremely tensile and extremely compressive loading conditions are
      determined for pipe stress analysis, and failure criteria based on flow stress is
      employed to perform stress analysis for pipe girth weld with pore defect. Results
      show that pipe girth welding stresses of pores at various radial locations are
      similar. Whereas, stress for pores of different sharpness varied significantly.
      Besides, tolerance capability of API 5L X90 grade pipe to pore defect of girth
      weld is lower than that of API 5L X80 grade pipe, and size control index of 3 mm
      related to pore defect in current standards is applicable to API 5L X80 and X90
      grade girth welded pipes with radially non-sharp pore defects.

PMID- 29364987
TI  - Correction: Maternal Obesity in Early Pregnancy and Risk of Adverse Outcomes.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0080410.].

PMID- 29364985
TI  - The Socio-Moral Image Database (SMID): A novel stimulus set for the study of
      social, moral and affective processes.
AB  - A major obstacle for the design of rigorous, reproducible studies in moral
      psychology is the lack of suitable stimulus sets. Here, we present the Socio
      Moral Image Database (SMID), the largest standardized moral stimulus set
      assembled to date, containing 2,941 freely available photographic images,
      representing a wide range of morally (and affectively) positive, negative and
      neutral content. The SMID was validated with over 820,525 individual judgments
      from 2,716 participants, with normative ratings currently available for all
      images on affective valence and arousal, moral wrongness, and relevance to each
      of the five moral values posited by Moral Foundations Theory. We present a
      thorough analysis of the SMID regarding (1) inter-rater consensus, (2) rating
      precision, and (3) breadth and variability of moral content. Additionally, we
      provide recommendations for use aimed at efficient study design and
      reproducibility, and outline planned extensions to the database. We anticipate
      that the SMID will serve as a useful resource for psychological, neuroscientific
      and computational (e.g., natural language processing or computer vision)
      investigations of social, moral and affective processes. The SMID images, along
      with associated normative data and additional resources are available at
      https://osf.io/2rqad/.

PMID- 29364988
TI  - Socio-affective touch expression database.
AB  - Socio-affective touch communication conveys a vast amount of information about
      emotions and intentions in social contexts. In spite of the complexity of the
      socio-affective touch expressions we use daily, previous studies addressed only a
      few aspects of social touch mainly focusing on hedonics, such as stroking,
      leaving a wide range of social touch behaviour unexplored. To overcome this
      limit, we present the Socio-Affective Touch Expression Database (SATED), which
      includes a large range of dynamic interpersonal socio-affective touch events
      varying in valence and arousal. The original database contained 26 different
      social touch expressions each performed by three actor pairs. To validate each
      touch expression, we conducted two behavioural experiments investigating
      perceived naturalness and affective values. Based on the rated naturalness and
      valence, 13 socio-affective touch expressions along with 12 corresponding non
      social touch events were selected as a complete set, achieving 75 video clips in
      total. Moreover, we quantified motion energy for each touch expression to
      investigate its intrinsic correlations with perceived affective values and its
      similarity among actor- and action-pairs. As a result, the touch expression
      database is not only systematically defined and well-controlled, but also
      spontaneous and natural, while eliciting clear affective responses. This database
      will allow a fine-grained investigation of complex interpersonal socio-affective
      touch in the realm of social psychology and neuroscience along with potential
      application areas in affective computing and neighbouring fields.

PMID- 29364990
TI  - Correction: Kar3Vik1 Uses a Minus-End Directed Powerstroke for Movement along
      Microtubules.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0053792.].

PMID- 29364989
TI  - Towards the description of livestock mobility in Sahelian Africa: Some results
      from a survey in Mauritania.
AB  - Understanding spatio-temporal patterns of host mobility is a key factor to
      prevent and control animal and human diseases. This is utterly important in low
      income countries, where animal disease epidemics have strong socio-economic
      impacts. In this article we analyzed a livestock mobility database, whose data
      have been collected by the Centre National d'Elevage et de Recherches
      Veterinaires (CNERV) Mauritania, to describe its patterns and temporal evolution.
      Data were collected through phone and face-to-face interviews in almost all the
      regions in Mauritania over a period of roughly two weeks during June 2015. The
      analysis has shown the existence of two mobility patterns throughout the year:
      the first related to routine movements from January to August; the second
      strictly connected to the religious festivity of Tabaski that in 2014 occurred at
      the beginning of October. These mobility patterns are different in terms of
      animals involved (fewer cattle and dromedaries are traded around Tabaski), the
      means of transportation (the volume of animals moved by truck raises around
      Tabaski) and destinations (most of the animals are traded nationally around
      Tabaski). Due to the differences between these two periods, public health
      officers, researchers and other stakeholders should take account of the time of
      the year when implementing vaccination campaigns or creating surveillance
      networks.

PMID- 29364991
TI  - Periprocedural Bridging Anticoagulation.

PMID- 29364992
TI  - Implementation of a Process for Initiating Naltrexone in Patients Hospitalized
      for Alcohol Detoxification or Withdrawal.
AB  - BACKGROUND: Naltrexone trials have demonstrated improved outcomes for patients
      with alcohol use disorders. Hospital initiation of naltrexone has had limited
      study. OBJECTIVE: To describe the implementation and impact of a process for
      counseling hospitalized patients with alcohol withdrawal about naltrexone.
      DESIGN: A pre-post study analysis. SETTING: A tertiary academic center. PATIENTS:
      Patients hospitalized for alcohol withdrawal. INTERVENTION: (1) Provider
      education about the efficacy and contraindications of naltrexone and (2)
      algorithms for evaluating patients for naltrexone. MEASUREMENTS: The percentages
      of patients counseled about and prescribed naltrexone before discharge and the
      percentages of pre- and postintervention patients with 30-day emergency
      department (ED) revisits and rehospitalizations. RESULTS: We identified 128
      patient encounters before and 114 after implementation. The percentage of
      patients counseled about naltrexone rose from 1.6% preimplementation to 63.2%
      postimplementation (P<.001); the percentage of patients prescribed naltrexone
      rose from 1.6% to 28.1% (P<.001). Comparing preintervention versus
      postintervention groups, there were no unadjusted differences in 30-day ED
      revisits (25.8% vs 19.3%; P=.23) or rehospitalizations (10.2% vs 11.4%; P=.75).
      When adjusted for demographics and comorbidities, postintervention patients had
      lower odds of 30-day ED revisits (odds ratio [OR]=0.47; 95% confidence interval
      [CI], 0.24-0.94) but no significant difference in rehospitalizations (OR=0.76;
      95% CI, 0.30-1.92). In subgroup analysis, postintervention patients counseled
      versus those not counseled about naltrexone were less likely to have 30-day ED
      revisits (9.7% vs 35.7%; P=.001) and rehospitalizations (2.8% vs 26.2%; P<.001).
      CONCLUSIONS: The implementation of a process for counseling patients hospitalized
      for alcohol withdrawal about using naltrexone for the maintenance of sobriety was
      associated with lower 30-day ED revisits but no statistically significant
      difference in rehospitalizations.

PMID- 29364993
TI  - Ab initio surface properties of Ag-Sn alloys: implications for lead-free
      soldering.
AB  - Ag and Sn are the major components of solder alloys adopted to assemble printed
      circuit boards. The qualities that make them the alloys of choice for the modern
      electronic industry are related to their physical and chemical properties. For
      corrosion resistance and solderability, surface properties are particularly
      important. Yet, atomic-level information about the surfaces of these alloys is
      not known. Here we fill this gap by presenting an extensive ab initio
      investigation of composition, energetics, structure and reactivity of Ag-Sn alloy
      surfaces. The structure and stability of various surfaces is evaluated, and the
      main factors determining the energetics of surface formation are uncovered.
      Oxygen and sulphur chemisorptions are studied and discussed in the framework of
      corrosion tendency, an important issue for printed circuit boards. Adsorption
      energy trends are rationalized based on the analysis of structural and electronic
      features.

PMID- 29364994
TI  - JBP and bibliometric indices.

PMID- 29364995
TI  - The difficult task of searching for tools that help predict mechanical ventilator
      weaning success.

PMID- 29364996
TI  - Thickening of the tracheal wall.

PMID- 29364997
TI  - Prognostic studies for health care decision making.

PMID- 29364998
TI  - Usefulness of radiological signs of pulmonary congestion in predicting failed
      spontaneous breathing trials.
AB  - Inspiratory fall in intrathoracic pressure during a spontaneous breathing trial
      (SBT) may precipitate cardiac dysfunction and acute pulmonary edema. We aimed to
      determine the relationship between radiological signs of pulmonary congestion
      prior to an SBT and weaning outcomes. This was a post hoc analysis of a
      prospective cohort study involving patients in an adult medical-surgical ICU. All
      enrolled individuals met the eligibility criteria for liberation from mechanical
      ventilation. Tracheostomized subjects were excluded. The primary endpoint was SBT
      failure, defined as the inability to tolerate a T-piece trial for 30-120 min. An
      attending radiologist applied a radiological score on interpretation of digital
      chest X-rays performed before the SBT. A total of 170 T-piece trials were carried
      out; SBT failure occurred in 28 trials (16.4%), and 133 subjects (78.3%) were
      extubated at first attempt. Radiological scores were similar between SBT-failure
      and SBT-success groups (median [interquartile range] = 3 [2-4] points vs. 3 [2-4]
      points; p = 0.15), which, according to the score criteria, represented
      interstitial lung congestion. The analysis of ROC curves demonstrated poor
      accuracy (area under the curve = 0.58) of chest x-rays findings of congestion
      prior to the SBT for discriminating between SBT failure and SBT success. No
      correlation was found between fluid balance in the 48 h preceding the SBT and
      radiological score results (rho = -0.13). Radiological findings of pulmonary
      congestion should not delay SBT indication, given that they did not predict
      weaning failure in the medical-surgical critically ill population.
      (ClinicalTrials.gov identifier: NCT02022839 [http://www.clinicaltrials.gov/]).

PMID- 29364999
TI  - Laryngotracheobronchial papillomatosis: chest CT findings.
AB  - To evaluate the findings on chest CTs in 16 patients (8 men and 8 women) with
      laryngotracheobronchial papillomatosis. This was a retrospective study involving
      patients ranging from 2 to 72 years of age. The evaluation of the CT scans was
      independently performed by two observers, and discordant results were resolved by
      consensus. The inclusion criteria were presence of abnormalities on the CT scans,
      and the diagnosis was confirmed by anatomopathological examination of the
      papillomatous lesions. The most common symptoms were hoarseness, cough, dyspnea,
      and recurrent respiratory infections. The major CT findings were nodular
      formations in the trachea, solid or cavitated nodules in the lung parenchyma, air
      trapping, masses, and consolidation. Nodular formations in the trachea were
      observed in 14 patients (87.5%). Only 2 patients had lesions in lung parenchyma
      without tracheal involvement. Only 1 patient had no pulmonary dissemination of
      the disease, showing airway involvement only. Solid and cavitated lung nodules
      were observed in 14 patients (87.5%) and 13 (81.2%), respectively. Masses were
      observed in 6 patients (37.5%); air trapping, in 3 (18.7%); consolidation in 3
      (18.7%); and pleural effusion, in 1 (6.3%). Pulmonary involvement was bilateral
      in all cases. The most common tomography findings were nodular formations in the
      trachea, as well as solid or cavitated nodules and masses in the lung parenchyma.
      Malignant transformation of the lesions was observed in 5 cases.

PMID- 29365000
TI  - Translation and cultural adaptation of a specific instrument for measuring asthma
      control and asthma status: the Asthma Control and Communication Instrument.
AB  - OBJECTIVE: To translate the Asthma Control and Communication Instrument (ACCI) to
      Portuguese and adapt it for use in Brazil. METHODS: The ACCI was translated to
      Portuguese and adapted for use in Brazil in accordance with internationally
      accepted guidelines. The protocol included the following steps: permission and
      rights of use granted by the original author; translation of the ACCI from
      English to Portuguese; reconciliation; back-translation; review and harmonization
      of the back-translation; approval from the original author; review of the
      Portuguese version of the ACCI by an expert panel; cognitive debriefing (the
      clarity, understandability, and acceptability of the translated version being
      tested in a sample of the target population); and reconciliation and preparation
      of the final version. RESULTS: During the cognitive debriefing process, 41 asthma
      patients meeting the inclusion criteria completed the ACCI and evaluated the
      clarity of the questions/statements. The clarity index for all ACCI items was >
      0.9, meaning that all items were considered to be clear. CONCLUSIONS: The ACCI
      was successfully translated to Portuguese and culturally adapted for use in
      Brazil, the translated version maintaining the psychometric properties of the
      original version. The ACCI can be used in clinical practice because it is easy to
      understand and easily applied.

PMID- 29365001
TI  - High-resolution computed tomography findings of pulmonary tuberculosis in lung
      transplant recipients.
AB  - OBJECTIVE: Respiratory infections constitute a major cause of morbidity and
      mortality in solid organ transplant recipients. The incidence of pulmonary
      tuberculosis is high among such patients. On imaging, tuberculosis has various
      presentations. Greater understanding of those presentations could reduce the
      impact of the disease by facilitating early diagnosis. Therefore, we attempted to
      describe the HRCT patterns of pulmonary tuberculosis in lung transplant
      recipients. METHODS: From two hospitals in southern Brazil, we collected the
      following data on lung transplant recipients who developed pulmonary
      tuberculosis: gender; age; symptoms; the lung disease that led to
      transplantation; HRCT pattern; distribution of findings; time from
      transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings
      were classified as miliary nodules; cavitation and centrilobular nodules with a
      tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal
      lymph node enlargement; or pleural effusion. RESULTS: We evaluated 402 lung
      transplant recipients, 19 of whom developed pulmonary tuberculosis after
      transplantation. Among those 19 patients, the most common HRCT patterns were
      ground-glass attenuation with consolidation (in 42%); cavitation and
      centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal
      lymph node enlargement (in 15.7%). Among the patients with cavitation and
      centrilobular nodules with a tree-in-bud pattern, the distribution was within the
      upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one
      year mortality was 47.3%. CONCLUSIONS: The predominant HRCT pattern was ground
      glass attenuation with consolidation, followed by cavitation and centrilobular
      nodules with a tree-in-bud pattern. These findings are similar to those reported
      for immunocompetent patients with pulmonary tuberculosis and considerably
      different from those reported for AIDS patients with the same disease.

PMID- 29365002
TI  - Pneumonia mortality trends in all Brazilian geographical regions between 1996 and
      2012.
AB  - OBJECTIVE: To analyze the temporal trends in pneumonia mortality rates
      (standardized by age, using the 2010 population of Brazil as the standard) in all
      Brazilian geographical regions between 1996 and 2012. METHODS: This was an
      ecological time-series study examining secondary data from the Mortality Database
      maintained by the Information Technology Department of the Brazilian Unified
      Health Care System. Polynomial and joinpoint regression models, and corresponding
      95% CIs, were used for trend analysis. RESULTS: The pneumonia mortality rates in
      the South, Southeast, and Central-West showed a decreasing behavior until 2000,
      followed by increases, whereas, in the North and Northeast, they showed
      increasing trends virtually throughout the period studied. There was variation in
      annual percent change in pneumonia mortality rates in all regions except the
      North. The Central-West had the greatest decrease in annual percent change
      between 1996 and 2000, followed by an increase of the same magnitude until 2005.
      The 80 years and over age group was the one most influencing the trend behavior
      of pneumonia mortality rates in all regions. CONCLUSIONS: In general, pneumonia
      mortality trends reversed, with an important increase occurring in the years
      after 2000.

PMID- 29365003
TI  - Can the six-minute walk distance predict the occurrence of acute exacerbations of
      COPD in patients in Brazil?
AB  - OBJECTIVE: To evaluate whether a six-minute walk distance (6MWD) of < 80% of the
      predicted value can predict the occurrence of acute exacerbations of COPD in
      patients in Brazil over a 2-year period. METHODS: This was a retrospective cross
      sectional study involving 50 COPD patients in Brazil. At enrollment,
      anthropometric data were collected and patients were assessed for pulmonary
      function (by spirometry) and functional exercise capacity (by the 6MWD). The
      patients were subsequently divided into two groups: 6MWD <= 80% of predicted and
      6MWD > 80% of predicted. The occurrence of acute exacerbations of COPD over 2
      years was identified by analyzing medical records and contacting patients by
      telephone. RESULTS: In the sample as a whole, there was moderate-to-severe
      airflow obstruction (mean FEV1 = 41 +/- 12% of predicted) and the mean 6MWD was
      469 +/- 60 m (86 +/- 10% of predicted). Over the 2-year follow-up period, 25
      patients (50%) experienced acute exacerbations of COPD. The Kaplan-Meier method
      showed that the patients in whom the 6MWD was <= 80% of predicted were more
      likely to have exacerbations than were those in whom the 6MWD was > 80% of
      predicted (p = 0.01), whereas the Cox regression model showed that the former
      were 2.6 times as likely to have an exacerbation over a 2-year period as were the
      latter (p = 0.02). CONCLUSIONS: In Brazil, the 6MWD can predict acute
      exacerbations of COPD over a 2-year period. The risk of experiencing an acute
      exacerbation of COPD within 2 years is more than twice as high in patients in
      whom the 6MWD is <= 80% of predicted.

PMID- 29365004
TI  - Sleep quality in medical students: a comparison across the various phases of the
      medical course.
AB  - OBJECTIVE: To evaluate and compare subjective sleep quality in medical students
      across the various phases of the medical course. METHODS: This was a cross
      sectional study involving medical undergraduates at one medical school in the
      city of Botucatu, Brazil. All first- to sixth-year students were invited to
      complete the Pittsburgh Sleep Quality Index, which has been validated for use in
      Brazil. Participants were divided into three groups according to the phase of the
      medical course: group A (first- and second-years); group B (third- and fourth
      years); and group C (fifth- and sixth-years). The results obtained for the
      instrument components were analyzed for the total sample and for the groups.
      RESULTS: Of the 540 students invited to participate, 372 completed the instrument
      fully. Of those, 147 (39.5%) reported their sleep quality to be either very or
      fairly bad; 110 (29.5%) reported taking more than 30 min to fall asleep; 253
      (68.0%) reported sleeping 6-7 h per night; 327 (87.9%) reported adequate sleep
      efficiency; 315 (84.6%) reported no sleep disturbances; 32 (8.6%) reported using
      sleeping medication; and 137 (36.9%) reported difficulty staying awake during the
      day at least once a week. Group comparison revealed that students in group A had
      worse subjective sleep quality and greater daytime dysfunction than did those in
      groups B and C. CONCLUSIONS: Medical students seem to be more exposed to sleep
      disturbance than other university students, and first- and second-years are more
      affected than those in other class years because they have worse subjective sleep
      quality. Active interventions should be implemented to improve sleep hygiene in
      medical students.

PMID- 29365006
TI  - Multislice CT in the diagnosis of bronchopleural fistula.

PMID- 29365007
TI  - The reversed halo sign: also think about chronic eosinophilic pneumonia.

PMID- 29365005
TI  - Recommendations for the pharmacological treatment of COPD: questions and answers.
AB  - The treatment of COPD has become increasingly effective. Measures that range from
      behavioral changes, reduction in exposure to risk factors, education about the
      disease and its course, rehabilitation, oxygen therapy, management of
      comorbidities, and surgical and pharmacological treatments to end-of-life care
      allow health professionals to provide a personalized and effective therapy. The
      pharmacological treatment of COPD is one of the cornerstones of COPD management,
      and there have been many advances in this area in recent years. Given the greater
      availability of drugs and therapeutic combinations, it has become increasingly
      challenging to know the indications for, limitations of, and potential risks and
      benefits of each treatment modality. In order to critically evaluate recent
      evidence and systematize the major questions regarding the pharmacological
      treatment of COPD, 24 specialists from all over Brazil gathered to develop the
      present recommendations. A visual guide was developed for the classification and
      treatment of COPD, both of which were adapted to fit the situation in Brazil. Ten
      questions were selected on the basis of their relevance in clinical practice.
      They address the classification, definitions, treatment, and evidence available
      for each drug or drug combination. Each question was answered by two specialists,
      and then the answers were consolidated in two phases: review and consensus by all
      participants. The questions answered are practical questions and help select from
      among the many options the best treatment for each patient and his/her
      peculiarities.

PMID- 29365008
TI  - Pneumothorax: between the beach and the stratosphere.

PMID- 29365009
TI  - A Dietary Pattern of Higher Fish, Egg, Milk, Nut, Vegetable and Fruit, and Lower
      Salt Intake Correlates With the Prevalence and Control of Hypertension.
AB  - BACKGROUND: The effects of food on the prevalence and control of hypertension are
      unclear. We aimed to investigate whether a dietary pattern of higher fish, egg,
      milk, nut, vegetable and fruit consumption, and lower salt intake was associated
      with hypertension in China. METHODS: A total of 15,303 subjects were recruited
      from September 2012 to December 2014. Groups with (n = 1,604) and without (n =
      13,660) hypertension were formed for a case-control study. The hypertensive
      participants were classified into the controlled blood pressure (BP) subgroup (n
      = 397) and the uncontrolled BP subgroup (n = 1,207). Data on the average weekly
      intake of fish, eggs, milk, nuts, vegetables, fruit, and salt in the past year
      were collected. Higher intake was defined as greater than or equal to median food
      intake. RESULTS: Higher fish, egg, milk, nut, vegetable, and fruit intake
      correlated with lower hypertension prevalence, and fish and fruit intake were the
      strongest associated factors. Meanwhile, higher fruit intake, the highest
      quartile of egg or milk intake, and the lowest quartile of salt intake correlated
      with better BP control. Furthermore, the dietary pattern was associated with
      lower hypertension prevalence (odds ratio [OR]: 0.88, 95% confidence interval
      [CI]: 0.84-0.92; P < 0.001) and better BP control (OR: 1.11, 95% CI: 1.03-1.21; P
      = 0.011). However, the dietary pattern did not correlate with BP control after
      excluding fruit intake. CONCLUSIONS: The dietary pattern correlated with lower
      hypertension prevalence and better BP control, and its association with BP
      control might be driven by higher fruit consumption.

PMID- 29365011
TI  - Incorrect Degree in Byline.

PMID- 29365012
TI  - Sun Protection Behaviors in Head Start and Other Early Childhood Education
      Programs in Illinois.
AB  - Importance: Sun safety attitudes developed in early childhood can reduce lifetime
      UV radiation exposure and the risk of skin cancer. Objective: To assess the
      current policies, practices, and attitudes among caregivers regarding sun
      protection in children aged 2 to 6 years. Design, Setting, and Participants: A
      survey of 202 administrators or managers and teachers of Illinois Head
      Start/Early Head Start (HS/EHS) and day care centers was conducted from July 3
      through 21, 2017. Organizations were randomly selected from 4 lists of urban,
      suburban, town, and rural locations and stratified to ensure population-based
      proportional representation of the Illinois population vulnerable to UV exposure.
      Program administrators or managers participated in a 5- to 10-minute telephone
      interview that assessed importance of health and sun protection behaviors,
      program practices, and demographic characteristics. Data analysis was conducted
      August 2, 2017. Main Outcomes and Measures: Outcomes included attitudes toward
      the importance of health behaviors in comparison with sun protective behaviors,
      reported use of sun protection (seeking shade, scheduling outdoor activities, sun
      protective clothing, and sunscreen practices), and sunburn prevalence. Results:
      Respondents (from 102 HS/EHS programs with 52% boys overall and a mean [SD] child
      age of 2.5 [0.5] y and 100 day care programs with 49% boys and age of 2.3 [0.4]
      y) stated that the 3 most important habits were good nutrition (66 [64.7%]
      HS/EHS, 71 [71.0%] day care), adequate exercise (41 [40.2%] HS/EHS, 55 [55.0%]
      day care), and brushing teeth (35 [34.3%] HS/EHS, 38 [38.0 %] day care).
      Scheduling outdoor activities to avoid peak sun intensity was performed less by
      HS/EHS programs (46 [45.1%]) in comparison with day care programs (71 [71.0%]; P
      < .001). Sunscreen was provided for students in 109 programs, but 84 (77.1%) did
      not allow children to apply sunscreen themselves. Half of the programs (100 of
      202 [50.0%]) used spray sunscreen to avoid unnecessarily touching children. Most
      programs did not report any children having sunburns (129 [63.9%]) and followed
      heat index guidelines (114 [56.4%]). Conclusions and Relevance: Administrators
      and teachers did not identify sun safety as one of the most important health
      habits. While spray sunscreen was used frequently, avoiding spraying sunscreen
      directly on a child's face, which may get it into the child's eyes, was not done.
      The heat index was widely used to determine outdoor playtime. Adopting UV index
      policies could help prevent sunburns in early spring when the heat index is low
      but UV index is high. Dermatologists may assume responsibility for educating the
      administrators about the danger of spraying sunscreen into a child's face and the
      advantage of using the UV index to determine when sun protection is needed.

PMID- 29365010
TI  - T-Cell Large Granular Lymphocytic Leukemia and Coexisting B-Cell Lymphomas: A
      Study From the Bone Marrow Pathology Group.
AB  - Objective: T-cell large granular lymphocytic (T-LGL) leukemia is associated with
      B-cell lymphomas (BCLs), especially small BCLs. We aimed to explore and expand
      upon its association with BCLs. Methods: We retrospectively studied
      clinicopathologic features of T-LGL leukemia patients with coexisting BCL from
      January 2001 to December 2016. Results: Among 432 patients with T-LGL leukemia,
      22 (5.1%) had an associated B-cell non-Hodgkin lymphoma. Thirteen (59%) patients
      had large and nine (41%) had small BCL. T-LGL leukemia occurred synchronously
      with BCL in five, preceded BCL in three, and followed BCL in 14 patients. Anemia
      was the most common cytopenia (68%). Only one patient had a history of rheumatoid
      arthritis. Conclusion: To our knowledge, this is the first multicenter study
      looking at the spectrum and incidence of BCLs in patients with T-LGL leukemia and
      highlights its association with large BCLs (3% of T-LGL leukemias).

PMID- 29365013
TI  - A New Year's Wish on Opioids.

PMID- 29365016
TI  - Incorrect Wave 4 Reporting.

PMID- 29365015
TI  - Progress Toward Elucidating Commonalities in Mental Disorders Using Brain Imaging
      and Publicly Available Data.

PMID- 29365014
TI  - Type of Menopause, Age at Menopause, and Risk of Developing Obstructive Sleep
      Apnea in Postmenopausal Women.
AB  - Despite established sex differences and longstanding hypotheses of sex hormone
      influence in the etiology of obstructive sleep apnea (OSA), we have found no
      studies that evaluated type of menopause and age at menopause, which affect
      postmenopausal hormonal milieu, in relation to OSA risk in women. We followed
      50,473 postmenopausal women from the Nurses' Health Study during 2002-2012 and
      53,827 postmenopausal women from the Nurses' Health Study II during 1995-2013,
      with 1,712 and 2,560 incident OSA diagnoses, respectively. Compared with natural
      menopause, the pooled hazard ratio for OSA was 1.27 (95% confidence interval
      (CI): 1.17, 1.38) for surgical menopause by hysterectomy/oophorectomy. The
      association remained the same after further accounting for age at menopause
      (hazard ratio = 1.26, 95% CI: 1.15, 1.38). The risk associated with surgical
      menopause was higher among women who were not obese as well as among women who
      never used hormone therapy (P for interaction < 0.05). Earlier menopause was
      associated with higher OSA risk prior to adjustment for type of menopause
      (comparing those aged <40 years versus those aged 50-54 years, hazard ratio =
      1.21, 95% CI: 1.08, 1.35; P for trend = 0.008), although no association was
      observed after the adjustment. Surgical as compared with natural menopause was
      independently associated with higher OSA risk in postmenopausal women. Our
      results provide additional evidence for a role for sex hormones, particularly
      abrupt hormonal changes, in modulating OSA risk.

PMID- 29365017
TI  - Association of Reperfusion With Brain Edema in Patients With Acute Ischemic
      Stroke: A Secondary Analysis of the MR CLEAN Trial.
AB  - Importance: It is uncertain whether therapeutic reperfusion with endovascular
      treatment yields more or less brain edema. Objective: To elucidate the
      association between reperfusion and brain edema. The secondary objectives were to
      evaluate whether brain edema could partially be responsible for worse outcomes in
      patients with later reperfusion or lower Alberta Stroke Program Early Computed
      Tomography Score. Design, Setting, and Participants: This was a post hoc analysis
      of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute
      Ischemic Stroke in the Netherlands (MR CLEAN), which was a prospective,
      randomized, multicenter clinical trial of endovascular treatment compared with
      conventional care of patients with acute anterior circulation ischemic stroke. Of
      502 patients enrolled from December 2010 to June 2014, 2 patients declined to
      participate. Additionally, exclusion criteria were absence of follow-up imaging
      or presence of parenchymal hematoma, resulting in 462 patients included in this
      study. Brain edema was assessed retrospectively, from December 10, 2016, to July
      24, 2017, by measuring midline shift (MLS) in all available follow-up scans.
      Observers were blinded to clinical data. Main Outcomes and Measures: Midline
      shift was assessed as present or absent and as a continuous variable. Reperfusion
      status was assessed by the modified thrombolysis in cerebral infarction score in
      the endovascular treatment arm. The modified arterial occlusive lesion score was
      used to evaluate the recanalization status in both arms. The modified Rankin
      scale score at 90 days was used for functional outcome. Results: Of 462 patients,
      the mean (SD) age was 65 (11) years, and 41.8% (n = 193) were women. Successful
      reperfusion and recanalization were associated with a reduced likelihood of
      having MLS (adjusted common odds ratio, 0.25; 95% CI, 0.12-0.53; P < .001 and
      adjusted common odds ratio, 0.34; 95% CI, 0.21-0.55; P < .001, respectively).
      Midline shift was partially responsible for worse modified Rankin scale scores in
      patients without reperfusion or recanalization (MLS changed the logistic
      regression coefficients by 30.3% and 12.6%, respectively). In patients with
      delayed reperfusion or lower Alberta Stroke Program Early Computed Tomography
      Score, MLS mediated part of the worse modified Rankin scale scores, corresponding
      to a change in the regression coefficient of 33.3% and 64.2%, respectively.
      Conclusions and Relevance: Successful reperfusion was associated with reduced
      MLS. This study identifies an additional benefit of reperfusion in relation to
      edema, as well as rescuing ischemic brain tissue at risk for infarction. Trial
      Registration: Netherlands Trial Registry number: NTR1804 and Current Controlled
      Trials number: ISRCTN10888758.

PMID- 29365018
TI  - Overexpression of Forkhead Box O3a and Its Association With Aggressive Phenotypes
      and Poor Prognosis in Human Hepatocellular Carcinoma.
AB  - Objectives: Recent research has demonstrated that forkhead box O3a (FoxO3a) may
      function as an oncogenic transcription factor. We sought to validate the
      clinicopathologic significance of FoxO3a expression in hepatocellular carcinoma
      (HCC). Methods: Western blotting and immunohistochemistry were used to determine
      FoxO3a expression. In vitro cell proliferation and migration assays were
      performed in a HepG2 cell line. Results: FoxO3a was overexpressed in 121 (64.71%)
      cases of HCC. FoxO3a overexpression was associated with aggressive phenotypes of
      HCC, such as histologic grade (P < .001), stage (P = .031), and small vessel
      invasion (P < .001). FoxO3a overexpression was also correlated with poor disease
      free survival in both univariate and multivariate survival analyses (P = .001 and
      P = .018, respectively). Downregulation of FoxO3a in a HepG2 cell line inhibited
      cell proliferation and migration. Conclusions: These results suggest a role for
      FoxO3a in HCC progression and support the potential use as a prognostic
      biomarker.

PMID- 29365019
TI  - Surgical Residents and Medical Malpractice-Reply.

PMID- 29365020
TI  - Transparency and Dermatologic Device Approval by the US Food and Drug
      Administration.
AB  - Importance: The US Food and Drug Administration approves Class III medical
      devices via the premarket approval pathway, often requiring clinical data on
      safety and efficacy. Manufacturers can submit incremental device changes via
      supplemental applications, which are not subjected to such vetting measures and
      can cause understudied changes that lead to drift from a device's original
      design. Objectives: To characterize the postapproval changes to Class III
      dermatologic devices and to evaluate inconsistencies in the use of the premarket
      approval pathway. Design, Setting, and Participants: This study was a cross
      sectional retrospective cohort analysis of a public US Food and Drug
      Administration database for premarket approval of devices. Included were
      dermatologic devices approved by the US Food and Drug Administration between
      January 1, 1980, and November 1, 2016, through the premarket pathway for device
      approval. Main Outcomes and Measures: Original devices were identified, and their
      supplements were characterized chronologically, by review track, and by
      modification category. Results: The 27 dermatologic devices studied consisted of
      14 injectables, 11 photodynamic therapies, a dermal replacement matrix, and a
      diagnostic imaging instrument. Supplemental applications are increasingly used:
      the data-requiring panel-track pathway was the least common approach (2.8% [16 of
      562 supplements]), while the 30-day track, which does not require clinical data,
      was most frequently used (42.5% [239 of 562 supplements]). Four devices (14.8%)
      underwent low-risk recalls (Class II or Class III), and 10 devices (37.0%) were
      voluntarily withdrawn. Conclusions and Relevance: As manufacturers make
      increasing use of supplemental applications, minor device changes may occur
      without supporting clinical data, which could pose a safety risk to patients.

PMID- 29365022
TI  - Anhydramnios in Patients With Pemphigoid Gestationis.

PMID- 29365021
TI  - Association of Resting Heart Rate and Temporal Changes in Heart Rate With
      Outcomes in Participants of the Atherosclerosis Risk in Communities Study.
AB  - Importance: Time-updated heart rate (HR) and temporal change in HR (DeltaHR) are
      associated with outcome in individuals with established heart failure (HF).
      Whether these factors are associated with outcomes in a community-based cohort is
      unclear. Objective: To determine whether the time-updated analysis of resting HR,
      defined as the most recent HR value measured before occurrence of an event or the
      end of study, and DeltaHR over time are associated with outcomes in a community
      based cohort. Design, Setting, and Participants: A total of 15 680 participants
      were enrolled in the Atherosclerosis Risk in Communities cohort study, with HR
      recorded at baseline and during 3 follow-up visits from 1987 to 1998, with a
      median interval between visits of 3.0 (interquartile range, 2.9-4.0) years. The
      DeltaHR was calculated by assessing a change in HR from the preceding visit.
      Participants were followed up until December 31, 2014, equating to 28 years of
      follow-up. The present study was conducted from March 2014 to June 2016 with
      updated analysis. Main Outcomes and Measures: Baseline HR, time-updated HR, and
      DeltaHR associated with outcomes, adjusted for established baseline and time
      updated risk factors and medications. The main outcomes measures included all
      cause mortality, incident HF, incident myocardial infarction, stroke, and
      cardiovascular and noncardiovascular death. Results: Of the 15 680 participants,
      8656 (55.2%) were women, mean (SD) age was 54 (6) years, and 4218 (26.9%) were
      African American. Time-updated HR and DeltaHR were associated with death,
      incident HF, incident myocardial infarction, stroke, and cardiovascular and
      noncardiovascular death compared with baseline HR. For example, a DeltaHR from
      the preceding visit was significantly associated with increased risk of all-cause
      mortality (adjusted hazard ratio, 1.12; 95% CI, 1.10-1.15; P < .001 for every 5
      bpm increase in HR from the preceding visit) and time-updated HR was also
      significantly associated with increased risk of all-cause mortality (adjusted
      hazard ratio, 1.14; 95% CI, 1.12-1.17; P < .001 for every 5-bpm higher time
      updated HR). Conclusions and Relevance: In a community-based cohort, time-updated
      HR and DeltaHR are associated with mortality and nonfatal outcomes of incident
      HF, myocardial infarction, and stroke.

PMID- 29365023
TI  - Comparison of a Medical-Grade Monitor vs Commercial Off-the-Shelf Display for
      Mitotic Figure Enumeration and Small Object (Helicobacter pylori) Detection.
AB  - Objectives: To examine the performance of a commercial off-the-shelf (COTS)
      monitor vs a medical-grade (MG) monitor for small object enumeration in
      standardized digital pathology images. Methods: Pathologists reviewed 35 melanoma
      or 35 gastric biopsy images using the MG and COTS displays, with a 2-week washout
      period. Mitotic figure or Helicobacter pylori burden enumerations were compared
      with reference values reported by an expert subspecialist pathologist using a
      light microscope. Subjective evaluations of image color, brightness, and overall
      quality were also obtained. Results: There was substantial agreement between the
      mitotic counts obtained by the evaluating pathologists between monitors and the
      reference mitotic figure or H pylori burden assessments. Six of the nine
      evaluating pathologists subjectively evaluated the monitors as substantially
      similar. Conclusions: These findings are consistent with previous studies
      demonstrating that color calibration has limited impact on diagnostic accuracy
      and suggest that noncalibrated displays could be considered for fine assessment
      tasks.

PMID- 29365024
TI  - The US Food and Drug Administration's Approach for Safe Innovation of Medical
      Devices in Dermatology.

PMID- 29365027
TI  - Surgical Residents and Medical Malpractice.

PMID- 29365026
TI  - Association of Heritable Cognitive Ability and Psychopathology With White Matter
      Properties in Children and Adolescents.
AB  - Importance: Many mental disorders emerge during adolescence, which may reflect a
      cost of the potential for brain plasticity offered during this period. Brain
      dysconnectivity has been proposed as a common factor across diagnostic
      categories. Objective: To investigate the hypothesis that brain dysconnectivity
      is a transdiagnostic phenotype in adolescence with increased susceptibility and
      symptoms of psychiatric disease. Design, Setting, and Participants: We
      investigated clinical symptoms as well as cognitive function in 6487 individuals
      aged 8 to 21 years from November 1, 2009, to November 30, 2011, in the
      Philadelphia Neurodevelopmental Cohort and analyzed diffusion magnetic resonance
      imaging brain scans for 748 of the participants. Main Outcomes and Measures:
      Independent component analysis was used to derive dimensional psychopathology
      scores, and genome-wide complex trait analysis was used to estimate its
      heritability. Multimodal fusion simultaneously modeled contributions of the
      diffusion magnetic resonance imaging metrics fractional anisotropy, mean
      diffusivity, radial diffusivity, L1 (the principal diffusion tensor imaging eigen
      value), mode of anisotropy, as well as dominant and secondary fiber orientations,
      and structural connectivity density, and their association with general
      psychopathology and cognition. Results: Machine learning with 10-fold cross
      validation and permutation testing in 729 individuals (aged 8 to 22 years; mean
      [SD] age, 15.1 [3.3] years; 343 females [46%]) revealed significant association
      with general psychopathology levels (r = 0.24, P < .001) and cognition (r = 0.39,
      P < .001). A brain white matter pattern reflecting frontotemporal connectivity
      and crossing fibers in the uncinate fasciculus was the most associated feature
      for both traits. Univariate analysis across a range of clinical domains and
      cognitive test scores confirmed its transdiagnostic importance. Both the general
      psychopathology (16%; SE, 0.095; P = .05) and cognitive (18%; SE, 0.09; P = .01)
      factor were heritable and showed a negative genetic correlation. Conclusion and
      relevance: Dimensional and heritable general cognitive and psychopathology
      factors are associated with specific patterns of white matter properties,
      suggesting that dysconnectivity is a transdiagnostic brain-based phenotype in
      individuals with increased susceptibility and symptoms of psychiatric disorders.

PMID- 29365028
TI  - Incorrect Wave 4 Reporting.

PMID- 29365025
TI  - Incidence and Prognosis of Primary Gastrinomas in the Hepatobiliary Tract.

PMID- 29365029
TI  - Association of the Affordable Care Act Medicaid Expansion With Access to and
      Quality of Care for Surgical Conditions.

PMID- 29365030
TI  - Practical Diagnostic Approach to the Presence of Hyphae in Neuropathology
      Specimens With Three Illustrative Cases.
AB  - Objectives: Early and accurate diagnosis remains crucial in the therapeutic
      management of invasive central nervous system fungal infections. Different molds
      have intrinsic resistance to antifungal agents; thus, morphologic differentiation
      is helpful to clinicians. Methods: Using three examples, we present a guide on
      how to approach neuropathology specimens where hyphae are identified on initial
      histologic examination. Results: Hyphae can be classified into three basic
      groups: hyaline pauciseptated, hyaline septated, and pigmented or dematiaceous.
      The hyaline pauciseptated group includes the order of the Mucorales (previously
      Zygomyces) and is frequent in patients with decompensated diabetes and severe
      neutropenia. Aspergillus species constitutes the most frequently isolated mold in
      the hyaline septated group. However, other invasive hyaline septated molds
      include Fusarium species, which is frequently resistant to multiple antifungals,
      and Candida species Last, dematiaceous molds, although infrequent, can be found
      in neuropathology specimens, as happened during the outbreak of Exserohilum
      associated with manufacturing practices in a compound pharmacy. Conclusions:
      Categorizing hyphae into the three groups described allows pathologists to
      provide information that is useful for infectious disease treatment with an
      inclusive differential diagnosis of diverse fungal genera that share the same
      morphological features.

PMID- 29365031
TI  - Unravelling triple-negative breast cancer molecular heterogeneity using an
      integrative multiomic analysis.
AB  - Background: Recent efforts of genome-wide gene expression profiling analyses have
      improved our understanding of the biological complexity and diversity of triple
      negative breast cancers (TNBCs) reporting, at least six different molecular
      subtypes of TNBC namely Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory
      (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor
      (LAR). However, little is known regarding the potential driving molecular events
      within each subtype, their difference in survival and response to therapy.
      Further insight into the underlying genomic alterations is therefore needed.
      Patients and methods: This study was carried out using copy-number aberrations,
      somatic mutations and gene expression data derived from the Molecular Taxonomy of
      Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas.
      TNBC samples (n = 550) were classified according to Lehmann's molecular subtypes
      using the TNBCtype online subtyping tool (http://cbc.mc.vanderbilt.edu/tnbc/).
      Results: Each subtype showed significant clinic-pathological characteristic
      differences. Using a multivariate model, IM subtype showed to be associated with
      a better prognosis (HR = 0.68; CI = 0.46-0.99; P = 0.043) whereas LAR subtype was
      associated with a worst prognosis (HR = 1.47; CI = 1.0-2.14; P = 0.046). BL1
      subtype was found to be most genomically instable subtype with high TP53 mutation
      (92%) and copy-number deletion in genes involved in DNA repair mechanism (BRCA2,
      MDM2, PTEN, RB1 and TP53). LAR tumours were associated with higher mutational
      burden with significantly enriched mutations in PI3KCA (55%), AKT1 (13%) and CDH1
      (13%) genes. M and MSL subtypes were associated with higher signature score for
      angiogenesis. Finally, IM showed high expression levels of immune signatures and
      check-point inhibitor genes such as PD1, PDL1 and CTLA4. Conclusion: Our findings
      highlight for the first time the substantial genomic heterogeneity that
      characterize TNBC molecular subtypes, allowing for a better understanding of the
      disease biology as well as the identification of several candidate targets paving
      novel approaches for the development of anticancer therapeutics for TNBC.

PMID- 29365033
TI  - Guideline Update on Evaluation and Selection of Prosthetic Valves.

PMID- 29365032
TI  - Alcohol Content in the 'Hyper-Reality' MTV Show 'Geordie Shore'.
AB  - Aim: To quantify the occurrence of alcohol content, including alcohol branding,
      in the popular primetime television UK Reality TV show 'Geordie Shore' Series 11.
      Methods: A 1-min interval coding content analysis of alcohol content in the
      entire DVD Series 11 of 'Geordie Shore' (10 episodes). Occurrence of alcohol use,
      implied use, other alcohol reference/paraphernalia or branding was recorded.
      Results: All categories of alcohol were present in all episodes. 'Any alcohol'
      content occurred in 78%, 'actual alcohol use' in 30%, 'inferred alcohol use' in
      72%, and all 'other' alcohol references occurred in 59% of all coding intervals
      (ACIs), respectively. Brand appearances occurred in 23% of ACIs. The most
      frequently observed alcohol brand was Smirnoff which appeared in 43% of all brand
      appearances. Episodes categorized as suitable for viewing by adolescents below
      the legal drinking age of 18 years comprised of 61% of all brand appearances.
      Conclusions: Alcohol content, including branding, is highly prevalent in the UK
      Reality TV show 'Geordie Shore' Series 11. Two-thirds of all alcohol branding
      occurred in episodes age-rated by the British Board of Film Classification (BBFC)
      as suitable for viewers aged 15 years. The organizations OfCom, Advertising
      Standards Authority (ASA) and the Portman Group should implement more effective
      policies to reduce adolescent exposure to on-screen drinking. The drinks industry
      should consider demanding the withdrawal of their brands from the show. Short
      Summary: Alcohol content, including branding, is highly prevalent in the MTV
      reality TV show 'Geordie Shore' Series 11. Current alcohol regulation is failing
      to protect young viewers from exposure to such content.

PMID- 29365034
TI  - Simple Models and Ice Bucket Challenge Fuel Progress in ALS Treatment.

PMID- 29365035
TI  - Integrating the Genetics of Race and Ethnicity Into Cancer Research: Trailing
      Jane and John Q. Public.

PMID- 29365037
TI  - An update on the progress of transcriptomic profiles of human endometrial
      receptivity.
AB  - Despite advances in our understanding of fertility, implantation failure remains
      a significant problem for both spontaneous and assisted pregnancies. Most
      research efforts concerning the process of implantation are embryo-centric, with
      a dearth of studies on endometrial factors. Currently, there are no practical and
      effective diagnostic tools available to precisely predict endometrial
      receptivity. Transcriptomics, a field based on microarray technology, has a
      number of procedures for clinical applications, although the functional relevance
      of most identified genes remains unclear. Importantly, RNA sequencing will
      further improve the precision and broaden the clinical use of the transcriptome
      by detecting previously undiscovered genes, which could be used to further our
      understanding of endometrial receptivity. In this review, potential biomarkers
      based on endometrium gene expression profiles of human endometrial receptivity
      were described and compared in natural and stimulated cycles toward discovering
      future prospects for personalized medical approaches. The intent of this
      synthesis is to provide researchers, doctors, and clinicians in the field with a
      better understanding of endometrium receptivity, promote further study in the
      transcriptome in embryo implantation, and ultimately, improve pregnancy outcome.

PMID- 29365036
TI  - Real World Home Blood Pressure Variability in Over 56,000 Individuals With Nearly
      17 Million Measurements.
AB  - BACKGROUND: Using the data from 56,365 individuals, from 185 countries, and a
      Nokia Health Wireless blood pressure (BP) monitor, we investigated real-world
      characteristics of BP variability (BPV). METHODS: All included individuals self
      measured and uploaded their BP using Bluetooth at least 20 times over a period of
      >=1 month at a frequency and duration of their choosing. In total, 16,904,844 BP
      measurements were analyzed, with a median of 146 measurements per person
      (interquartile range [IQR] 73-321) over a median of 14 months (IQR 7-31). SD,
      coefficient of variation, maximum BP, and maximum minus minimum BP difference
      were all calculated as measures of BPV. RESULTS: BPV showed a distinct pattern,
      influenced by season of year, day of week, and time of day. BPV index was higher
      in females compared with males (P < 0.001) and increased with age (P < 0.001).
      Compared to the weekend, the weekday BPV index was significantly higher, and this
      finding was more prominent in females (P = 0.001). In multivariate analysis, BPV
      index were significantly associated with age, gender, geographic location, and
      mean BP values. CONCLUSION: Using the largest BP data set we are aware of, with
      the benefits and limitations of real-world measurement, we could show the pattern
      of BPV and provide reference values that may be helpful in understanding the
      nature of BPV as self-measurement at home becomes more common, and help guide
      individualized management.

PMID- 29365038
TI  - Mastopexy and Mastopexy-Augmentation.
AB  - Mastopexy and mastopexy-augmentation are aesthetic breast surgeries that seek to
      create youthful, beautiful appearing breasts. Age, hormonal changes, or weight
      loss can lead to alterations that require addressing the skin envelope and breast
      parenchyma. Many surgical approaches have been described including periareolar,
      vertical, and Wise pattern techniques, but most modern mastopexies include
      manipulation of the breast parenchyma to improve the longevity of breast ptosis
      correction. Mesh support of the ptotic breast is an extension of this paradigm
      shift and seeks to restore the lost strength of the support structures of the
      breast. Despite initial controversy, single stage mastopexy-augmentation has been
      demonstrated to be a safe option for appropriately selected and informed patients
      who desire both correction of shape and volume. Revisions may still be necessary
      based on patient and surgeon goals for correction. Evolving technologies will
      likely continue to enhance the ability of aesthetic plastic surgeons to provide
      pleasing, durable correction of breast ptosis.

PMID- 29365039
TI  - Response to "Comments on 'Long-Term Safety of Textured and Smooth Breast
      Implants' and a Plea to Abandon the Use of the MAUDE Database".

PMID- 29365040
TI  - Adjusting for unmeasured spatial confounding with distance adjusted propensity
      score matching.
AB  - Propensity score matching is a common tool for adjusting for observed confounding
      in observational studies, but is known to have limitations in the presence of
      unmeasured confounding. In many settings, researchers are confronted with
      spatially-indexed data where the relative locations of the observational units
      may serve as a useful proxy for unmeasured confounding that varies according to a
      spatial pattern. We develop a new method, termed distance adjusted propensity
      score matching (DAPSm) that incorporates information on units' spatial proximity
      into a propensity score matching procedure. We show that DAPSm can adjust for
      both observed and some forms of unobserved confounding and evaluate its
      performance relative to several other reasonable alternatives for incorporating
      spatial information into propensity score adjustment. The method is motivated by
      and applied to a comparative effectiveness investigation of power plant emission
      reduction technologies designed to reduce population exposure to ambient ozone
      pollution. Ultimately, DAPSm provides a framework for augmenting a "standard"
      propensity score analysis with information on spatial proximity and provides a
      transparent and principled way to assess the relative trade-offs of prioritizing
      observed confounding adjustment versus spatial proximity adjustment.

PMID- 29365041
TI  - The role of biomass allocation between lamina and petioles in a game of light
      competition in a dense stand of an annual plant.
AB  - Background and Aims: Models of plant three-dimensional (3-D) architecture have
      been used to find optimal morphological characteristics for light capture or
      carbon assimilation of a solitary plant. However, optimality theory is not
      necessarily useful to predict the advantageous strategy of an individual in dense
      stands, where light capture of an individual is influenced not only by its
      architecture but also by the architecture of its neighbours. Here, we analysed
      optimal and evolutionarily stable biomass allocation between the lamina and
      petiole (evolutionarily stable strategy; ESS) under various neighbour conditions
      using a 3-D simulation model based on the game theory. Methods: We obtained 3-D
      information of every leaf of actual Xanthium canadense plants grown in a dense
      stand using a ruler and a protractor. We calculated light capture and carbon
      assimilation of an individual plant when it stands alone and when it is
      surrounded by neighbours in the stand. We considered three trade-offs in petiole
      length and lamina area: biomass allocation, biomechanical constraints and
      photosynthesis. Optimal and evolutionarily stable biomass allocation between
      petiole and lamina were calculated under various neighbour conditions. Key
      Results: Optimal petiole length varied depending on the presence of neighbours
      and on the architecture of neighbours. The evolutionarily stable petiole length
      of plants in the stand tended to be longer than the optimal length of solitary
      plants. The mean of evolutionarily stable petiole length in the stand was similar
      to the real one. Trade-offs of biomechanical constraint and photosynthesis had
      minor effects on optimal and evolutionarily stable petiole length. Conclusion:
      Actual plants realize evolutionarily stable architecture in dense stands.
      Interestingly, there were multiple evolutionarily stable petiole lengths even in
      one stand, suggesting that plants with different architectures can coexist across
      plant communities.

PMID- 29365043
TI  - Why the Micromort Concept Falls Short in Breast Implant-Associated Anaplastic
      Large Cell Lymphoma (BIA-ALCL) Risk Analysis.

PMID- 29365042
TI  - Elevated androgen levels induce hyperinsulinemia through increase in Ins1
      transcription in pancreatic beta cells in female rats.
AB  - Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in
      adult females. We tested whether androgens dysregulate pancreatic beta cell
      function to induce hyperinsulinemia through transcriptional regulation of insulin
      gene (Ins) in the islets. Adult female Wistar rats implanted with
      dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined
      after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to
      that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia
      with increased HOMA-IR index in fasting state and glucose intolerance and
      exaggerated insulin responses following glucose tolerance test. DHT females had
      no change in islet number, size and beta cell proliferation/apoptosis but
      exhibited significant mitochondrial dysfunction (higher ADP/ATP ratio, decreased
      mtDNA copy number, increased reactive oxygen production and downregulation of
      mitochondrial biogenesis) and enhanced glucose-stimulated insulin secretion. Ins
      expression was increased in DHT islets. In vitro incubation of control islets
      with DHT dose dependently stimulated Ins transcription. Analysis of Ins1 gene
      revealed a putative androgen responsive element in the promoter. Chromatin
      immunoprecipitation assays showed that androgen receptors bind to this element in
      response to DHT stimulation. Furthermore, reporter assays showed that the
      promoter element is highly responsive to androgens. Insulin-stimulated glucose
      uptake in skeletal muscle was decreased with associated decrease in IRbeta
      expression in DHT females. Our studies identified a novel androgen-mediated
      mechanism for the control of Ins expression via transcriptional regulation
      providing a molecular mechanism linking elevated androgens and hyperinsulemia.
      Decreased IRbeta expression in the skeletal muscles may contribute, in part, to
      glucose intolerance in this model.

PMID- 29365044
TI  - Calcium oscillations in fertilized pig oocytes are associated with repetitive
      interactions between STIM1 and ORAI1.
AB  - The Ca2+ entry mechanism that sustains the Ca2+ oscillations in fertilized pig
      oocytes was investigated. Stromal interaction molecule 1 (STIM1) and ORAI1
      proteins tagged with various fluorophores were expressed in the oocytes. In some
      cells, the Ca2+ stores were depleted using cyclopiazonic acid (CPA); others were
      inseminated. Changes in the oocytes' cytosolic free Ca2+ concentration were
      monitored, while interaction between the expressed fusion proteins was
      investigated using fluorescence resonance energy transfer (FRET). Store depletion
      led to an increase of the FRET signal in oocytes co-expressing mVenus-STIM1 and
      mTurquoise2-ORAI1, indicating that Ca2+ release was followed by an interaction
      between these proteins. A similar FRET increase in response to CPA was also
      detected in oocytes co-expressing mVenus-STIM1 and mTurquoise2-STIM1, which is
      consistent with STIM1 forming punctae after store depletion. ML-9, an inhibitor
      that can interfere with STIM1 puncta formation, blocked store-operated Ca2+ entry
      (SOCE) induced by Ca2+ add-back after a CPA treatment; it also disrupted the Ca2+
      oscillations in fertilized oocytes. In addition, oocytes overexpressing mVenus
      STIM1 showed high-frequency Ca2+ oscillations when fertilized, arguing for an
      active role of the protein. High-frequency Ca2+ oscillations were also detected
      in fertilized oocytes co-expressing mVenus-STIM1 and mTurquoise2-ORAI1, and both
      of these high-frequency Ca2+ oscillations could be stopped by inhibitors of SOCE.
      Importantly, in oocytes co-expressing mVenus-STIM1 and mTurquoise2-ORAI1, we were
      also able to detect cyclic increases of the FRET signal indicating repetitive
      interactions between STIM1 and ORAI1. The results confirm the notion that in pig
      oocytes, SOCE is involved in the maintenance of the repetitive Ca2+ transients at
      fertilization.

PMID- 29365045
TI  - DincRNA: a comprehensive web-based bioinformatics toolkit for exploring disease
      associations and ncRNA function.
AB  - Summary: DincRNA aims to provide a comprehensive web-based bioinformatics toolkit
      to elucidate the entangled relationships among diseases and non-coding RNAs
      (ncRNAs) from the perspective of disease similarity. The quantitative way to
      illustrate relationships of pair-wise diseases always depends on their molecular
      mechanisms, and structures of the directed acyclic graph of Disease Ontology
      (DO). Corresponding methods for calculating similarity of pair-wise diseases
      involve Resnik's, Lin's, Wang's, PSB and SemFunSim methods. Recently, disease
      similarity was validated suitable for calculating functional similarities of
      ncRNAs and prioritizing ncRNA-disease pairs, and it has been widely applied for
      predicting the ncRNA function due to the limited biological knowledge from wet
      lab experiments of these RNAs. For this purpose, a large number of algorithms and
      priori knowledge need to be integrated. e.g. 'pair-wise best, pairs-average'
      (PBPA) and 'pair-wise all, pairs-maximum' (PAPM) methods for calculating
      functional similarities of ncRNAs, and random walk with restart (RWR) method for
      prioritizing ncRNA-disease pairs. To facilitate the exploration of disease
      associations and ncRNA function, DincRNA implemented all of the above eight
      algorithms based on DO and disease-related genes. Currently, it provides the
      function to query disease similarity scores, miRNA and lncRNA functional
      similarity scores, and the prioritization scores of lncRNA-disease and miRNA
      disease pairs. Availability and implementation: http://bio
      annotation.cn:18080/DincRNAClient/. Contact: biofomeng@hotmail.com or
      qhjiang@hit.edu.cn. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29365046
TI  - Commentary on: The Ideal Thigh: A Crowdsourcing-Based Assessment of Ideal Thigh
      Aesthetic and Implications for Gluteal Fat Grafting.

PMID- 29365047
TI  - Commentary on: Rejuvenating the Face: An Analysis of 100 Absorbable Suture
      Suspension Patients.

PMID- 29365048
TI  - Survival of LA-MRSA in Dust from Swine Farms.
AB  - Dust is suspected to be an important factor in transmission of livestock
      associated methicillin-resistant Staphylococcus aureus (LA-MRSA) between pigs and
      pig farmers and their families. The aim of this study was to determine the rate
      of decay for Staphylococcus aureus and LA-MRSA in dust from swine farms.
      Electrostatic dust fall collectors (EDCs) were used for passive sampling of
      settling airborne dust in 11 stable sections from six swine farms. Extraction,
      plating, identification, and enumeration of cultivable S. aureus and LA-MRSA from
      the EDCs were performed after storage for 0-30 days postsampling. The survival of
      S. aureus was measured in 196 dust samples from all farms, and data were used to
      estimate the decay constant lambda according to a model for exponential decay:
      N(t) = N0 * e-lambdat. The number of S. aureus colonies was up to 600-fold higher
      than the number of LA-MRSA colonies on MRSA selective agar. The data showed a
      good fit to the model (lambda = 0.13, r2 = 0.86) even with a large difference in
      initial concentrations of S. aureus between stables. The loads of S. aureus and
      LA-MRSA in the dust were significantly reduced by storage time, and the half-life
      was 5 days for both S. aureus and LA-MRSA. In dust samples with high initial
      concentrations, LA-MRSA and S. aureus could still be cultivated 30 days after
      sampling. On all farms MRSA isolates belonged to the clonal complex (CC) 398, and
      at one farm some isolates also belonged to CC30. A screening for other
      Staphylococcus species in the farm dust revealed 13 different species numerically
      dominated by Staphylococcus equorum. Based on the exponential decay model, S.
      equorum had a half-life of 4 days. In conclusion, the presence of MRSA in
      airborne dust from five of six farms indicates that dust might be an important
      vehicle for transmission of LA-MRSA. LA-MRSA and S. aureus was found to survive
      well in farm dust with half-lives of 5 days, and dependent on the initial
      concentration they could be found in farm dust for weeks. The 99.9% die-off rate
      was 66 days for LA-MRSA. Thus, farm dust can pose an exposure risk for humans in
      the farm environment, but also when transported to other environments. On the
      other hand, the risk will decrease by time. These results provide important
      knowledge to diminish spread from farm environments to other environments on,
      e.g., tools or clothing, and in relation to cleaning of emptied LA-MRSA-positive
      stables.

PMID- 29365049
TI  - Reproductive failure in mice expressing transgenic follicle-stimulating hormone
      is not caused by loss of oocyte quality.
AB  - Human female reproductive aging features declining ovarian follicle reserve and
      oocyte quality, and rising levels of circulating follicle-stimulating hormone
      (FSH). We determined the effects of elevated FSH on oocyte-embryo development in
      mature mice exhibiting premature infertility caused by progressively rising
      transgenic human FSH (TgFSH) levels. Oocyte-embryo developmental competence and
      quality were examined using oocyte maturation and aneuploidy rates, biomarkers of
      oocyte quality, and reciprocal embryo transfers assessed for implantation and
      pregnancy. In vitro maturation suggested that TgFSH exposure only hindered oocyte
      developmental competence in old females, as significantly more oocytes from >=12
      month-old TgFSH females remained at germinal vesicle stage compared with age
      matched control oocytes. Aneuploidy rates were equivalent in oocytes from aging
      TgFSH compared with wildtype females. Cumulus cell expression levels of candidate
      biomarker Inhba, Egfr, and Rgs2 transcripts were elevated in associated aneuploid
      vs euploid oocytes from both TgFSH and wildtype females. In vivo, embryos
      transferred from subfertile 6-month-old TgFSH females to wildtype recipients
      yielded normal implantation rates and more pups born compared with controls.
      Transfer of wildtype embryos rescued the fertility of 6-month-old TgFSH-recipient
      females, although pup birth weight was reduced in TgFSH vs wildtype recipients.
      Our current findings show that elevated FSH had minimal disruption of either
      embryo developmental capacity or uterine function when examined in isolation, and
      the subfertility of TgFSH female mice was not caused by altered oocyte aneuploidy
      or quality.

PMID- 29365051
TI  - The Nasal Ligaments and Tip Support in Rhinoplasty: An Anatomical Study.
AB  - Background: In 1971, Janeke and Wright1 published a now classic study on the
      support of the nasal tip in which they found four areas of anatomic support.
      These findings led to the "tripod concept" of tip support. Recently, surgeons
      have begun repairing and/or preserving the nasal ligaments as a method to control
      tip projection and rotation. Therefore, a reassessment of the nasal ligaments and
      tip support is warranted. Objectives: The present study was done to investigate
      the ligamentous and structural support of the nasal tip. Clinically, surgeons are
      aware of the role of the nasal ligaments and are beginning to utilize tip suture
      techniques to achieve greater tip refinement and long-term support. Methods:
      Anatomic studies were conducted on 24 fresh cadavers at the time of autopsy. The
      two groups consisted of the following: (1) group 1 included dissection of 10
      cadavers concentrated on the various ligaments of the nose; and (2) group 2
      involved dissections of 14 cadavers analyzing the relationship between the alar
      domes and the anterior septal angle (ASA). Results: Regarding the ligaments of
      the nose, we were able to consistently identify the following ligaments: (1)
      interdomal; (2) intercrural; (3) Pitanguy's midline; (4) pyriform; and (5) a
      scroll ligament complex consisting of the longitudinal and vertical scroll
      ligaments. We did not find two commonly accepted ligaments: (1) a "footplate
      ligament" from the footplate of the medial crus to the caudal septum; and (2) a
      "sesamoid ligament" attachment from the accessory cartilage to the pyriform
      aperture. Dissections done to study the relationship between the domes and ASA
      revealed that the domes projected an average of 5.7 mm (range, 2.2-9.6 mm) above
      the ASA and were longitudinally 5.5 mm (range, 2.9-9.5 mm) caudal to the ASA.
      Thus, there was no direct support from the ASA to the domes. Conclusions: It is
      our recommendation that surgeons should consider preservation of the nasal
      ligaments whenever possible and utilize them to manipulate tip projection,
      position, and rotation. Awareness of the relationship between the dome and the
      caudal septum will hopefully minimize problems with the tongue-in-groove
      operation.

PMID- 29365052
TI  - Commentary on: Effect of a Facial Muscle Exercise Device on Facial Rejuvenation.

PMID- 29365050
TI  - Effect of a Facial Muscle Exercise Device on Facial Rejuvenation.
AB  - Background: The efficacy of facial muscle exercises (FMEs) for facial
      rejuvenation is controversial. In the majority of previous studies,
      nonquantitative assessment tools were used to assess the benefits of FMEs.
      Objectives: This study examined the effectiveness of FMEs using a Pao (MTG,
      Nagoya, Japan) device to quantify facial rejuvenation. Methods: Fifty females
      were asked to perform FMEs using a Pao device for 30 seconds twice a day for 8
      weeks. Facial muscle thickness and cross-sectional area were measured
      sonographically. Facial surface distance, surface area, and volumes were
      determined using a laser scanning system before and after FME. Facial muscle
      thickness, cross-sectional area, midfacial surface distances, jawline surface
      distance, and lower facial surface area and volume were compared bilaterally
      before and after FME using a paired Student t test. Results: The cross-sectional
      areas of the zygomaticus major and digastric muscles increased significantly
      (right: P < 0.001, left: P = 0.015), while the midfacial surface distances in the
      middle (right: P = 0.005, left: P = 0.047) and lower (right: P = 0.028, left: P =
      0.019) planes as well as the jawline surface distances (right: P = 0.004, left: P
      = 0.003) decreased significantly after FME using the Pao device. The lower facial
      surface areas (right: P = 0.005, left: P = 0.006) and volumes (right: P = 0.001,
      left: P = 0.002) were also significantly reduced after FME using the Pao device.
      Conclusions: FME using the Pao device can increase facial muscle thickness and
      cross-sectional area, thus contributing to facial rejuvenation. Level of Evidence
      4: 

PMID- 29365053
TI  - Predicting progression from normal cognition to mild cognitive impairment for
      individuals at 5 years.
AB  - Recent evidence indicates that measures from cerebrospinal fluid, MRI scans and
      cognitive testing obtained from cognitively normal individuals can be used to
      predict likelihood of progression to mild cognitive impairment several years
      later, for groups of individuals. However, it remains unclear whether these
      measures are useful for predicting likelihood of progression for an individual.
      The increasing focus on early intervention in clinical trials for Alzheimer's
      disease emphasizes the importance of improving the ability to identify which
      cognitively normal individuals are more likely to progress over time, thus
      allowing researchers to efficiently screen participants, as well as determine the
      efficacy of any treatment intervention. The goal of this study was to determine
      which measures, obtained when individuals were cognitively normal, predict on an
      individual basis, the onset of clinical symptoms associated with a diagnosis of
      mild cognitive impairment due to Alzheimer's disease. Cognitively normal
      participants (n = 224, mean baseline age = 57 years) were evaluated with a range
      of measures, including: cerebrospinal fluid amyloid-beta and phosphorylated-tau,
      hippocampal and entorhinal cortex volume, cognitive tests scores and APOE
      genotype. They were then followed to determine which individuals developed mild
      cognitive impairment over time (mean follow-up = 11 years). The primary outcome
      was progression from normal cognition to the onset of clinical symptoms of mild
      cognitive impairment due to Alzheimer's disease at 5 years post-baseline. Time
      dependent receiver operating characteristic analyses examined the sensitivity and
      specificity of individual measures, and combinations of measures, as predictors
      of the outcome. Six measures, in combination, were the most parsimonious
      predictors of transition to mild cognitive impairment 5 years after baseline
      (area under the curve = 0.85; sensitivity = 0.80, specificity = 0.75). The
      addition of variables from each domain significantly improved the accuracy of
      prediction. The incremental accuracy of prediction achieved by adding individual
      measures or sets of measures successively to one another was also examined, as
      might be done when enrolling individuals in a clinical trial. The results
      indicate that biomarkers obtained when individuals are cognitively normal can be
      used to predict which individuals are likely to develop clinical symptoms at 5
      years post-baseline. As a number of the measures included in the study could also
      be used as subject selection criteria in a clinical trial, the findings also
      provide information about measures that would be useful for screening in a
      clinical trial aimed at individuals with preclinical Alzheimer's disease.

PMID- 29365054
TI  - GP73 promotes epithelial-mesenchymal transition and invasion partly by activating
      TGF-beta1/Smad2 signaling in hepatocellular carcinoma.
AB  - The transforming growth factor-beta1 (TGF-beta1) signaling pathways contribute to
      cell metastasis and epithelial-mesenchymal transition (EMT). Golgi protein 73
      (GP73), a type II transmembrane protein in the Golgi apparatus, was initially
      regarded as a potential biomarker for the diagnosis of hepatocellular carcinoma
      (HCC). Recently, it was reported that GP73 acts as a key oncogene by promoting
      HCC growth and metastasis. However, the role of GP73 in metastasis, especially
      when involving signaling pathways, is uncertain. Here, we report that GP73, which
      is upregulated in HCC tissues and cell lines, is associated with tumor size,
      tumor node metastasis stage, distant metastasis and vascular invasion. The
      ectopic overexpression of GP73 increased HCC cell invasion, EMT and metastasis
      both in vitro and in vivo. Conversely, GP73 knockdown inhibited invasion and EMT.
      Moreover, GP73 enhanced p-Smad2 and p-Smad3 levels by mediating TGF-beta1, thus
      leading to the promotion of EMT and invasion in HCC cells. In contrast, we used
      SB431542 (SB) to repress p-Smad2 and p-Smad3 expression, which resulted in a
      reversion of EMT. Furthermore, when the TGF-beta1/Smad pathway was blocked,
      upregulation of GP73 still caused an enhanced EMT and invasion, and
      downregulation of GP73 resulted in a decreased in EMT and invasion. In clinical
      HCC samples, GP73 positively correlated with TGF-beta1/Smad2, which was
      upregulated in HCC. Taken together, our findings highlight the important role of
      GP73 in regulating EMT and metastasis in HCC partly by targeting TGF-beta1/Smad2
      signaling, suggesting that GP73 may represent a novel potential therapeutic
      target and prognostic marker for the treatment and diagnosis of HCC.

PMID- 29365055
TI  - Comments on "Long-Term Safety of Textured and Smooth Breast Implants" and a Plea
      to Abandon the Use of the MAUDE Database.

PMID- 29365056
TI  - The Ideal Thigh: A Crowdsourcing-Based Assessment of Ideal Thigh Aesthetic and
      Implications for Gluteal Fat Grafting.
AB  - Background: As the popularity of aesthetic gluteoplasty continues to grow, there
      is renewed focus on defining the ideal buttocks. However, the literature lacks
      studies characterizing an ideal thigh, despite the impact of thigh contour on
      overall gluteal aesthetic. Objectives: The authors performed the first population
      analysis of the characteristics of perception of attractive thighs, to identify a
      role for fat grafting of the thigh in gluteoplasty. Methods: Survey images were
      digitally modified to create thighs of varying widths and angles relative to
      fixed buttocks. Thigh-to-buttock ratios and the buttock-thigh junction were
      studied. Data were stratified and analyzed according to age, gender, and
      ethnicity of the respondents. Amazon Mechanical Turk was used as a novel
      crowdsourcing platform for surveying aesthetic preferences. Results: A total of
      1034 responses were included of whom 54.4% were male, and 45.6% were female. All
      age groups and ethnicities were represented. Overall, 43.8% of respondents
      preferred the widest buttock-thick junction angle on posterior view. There was no
      clear preference between larger or smaller thigh-to-hip ratios on lateral view.
      Conclusions: Characteristics of the ideal thigh include wider thighs with greater
      horizontal projection, creating a more natural contour from the augmented
      buttock. These findings represent a paradigm shift from the traditionally assumed
      preference for slender thighs. Plastic surgeons should carefully consider thigh
      anatomy in their gluteal augmentation patients, as simultaneous thigh
      augmentation may lead to a more aesthetically pleasing outcome. Further research
      is needed into best practices and techniques to attain ideal thigh proportions.

PMID- 29365057
TI  - Computational drug repositioning using low-rank matrix approximation and
      randomized algorithms.
AB  - Motivation: Computational drug repositioning is an important and efficient
      approach towards identifying novel treatments for diseases in drug discovery. The
      emergence of large-scale, heterogeneous biological and biomedical datasets has
      provided an unprecedented opportunity for developing computational drug
      repositioning methods. The drug repositioning problem can be modeled as a
      recommendation system that recommends novel treatments based on known drug
      disease associations. The formulation under this recommendation system is matrix
      completion, assuming that the hidden factors contributing to drug-disease
      associations are highly correlated and thus the corresponding data matrix is low
      rank. Under this assumption, the matrix completion algorithm fills out the
      unknown entries in the drug-disease matrix by constructing a low-rank matrix
      approximation, where new drug-disease associations having not been validated can
      be screened. Results: In this work, we propose a drug repositioning
      recommendation system (DRRS) to predict novel drug indications by integrating
      related data sources and validated information of drugs and diseases. Firstly, we
      construct a heterogeneous drug-disease interaction network by integrating drug
      drug, disease-disease and drug-disease networks. The heterogeneous network is
      represented by a large drug-disease adjacency matrix, whose entries include drug
      pairs, disease pairs, known drug-disease interaction pairs and unknown drug
      disease pairs. Then, we adopt a fast Singular Value Thresholding (SVT) algorithm
      to complete the drug-disease adjacency matrix with predicted scores for unknown
      drug-disease pairs. The comprehensive experimental results show that DRRS
      improves the prediction accuracy compared with the other state-of-the-art
      approaches. In addition, case studies for several selected drugs further
      demonstrate the practical usefulness of the proposed method. Availability and
      implementation:
      http://bioinformatics.csu.edu.cn/resources/softs/DrugRepositioning/DRRS/index.htm
      . Contact: yaohang@cs.odu.edu or jxwang@mail.csu.edu.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29365058
TI  - Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label
      multicentre randomised trial.
AB  - Background: [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed
      tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of
      colorectal cancer (CRC). Our objective was to determine whether adding routine 6
      monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes
      and to assess the effect on costs. Patients and methods: In this open-label
      multicentre trial, patients in remission of CRC (stage II perforated, stage III,
      or stage IV) after curative surgery were randomly assigned (1 : 1) to usual
      monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver
      ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or
      with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed
      each patient's data every 3 months and classified the recurrence status as
      yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible
      and with chemotherapy otherwise. The primary end point was treatment failure
      defined as unresectable recurrence or death. Relative risks were estimated, and
      survival was analysed using the Kaplan-Meier method, log-rank test, and Cox
      models. Direct costs were compared. Results: Of the 239 enrolled patients, 120
      were in the intervention arm and 119 in the control arm. The failure rate was
      29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and
      23.7% (27 unresectable recurrences and 1 death) in the control group (relative
      risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate
      analysis also showed no significant difference (hazards ratio, 1.33; 95%
      confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of
      unresectable recurrence (months) was significantly shorter in the intervention
      group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in
      the intervention group (18 192 +/- 27 679 ? versus 11 131 +/- 13  ?, P < 0.033).
      Conclusion: 18FDG-PET/CT, when added every 6 months, increased costs without
      decreasing treatment failure rates in patients in remission of CRC. The control
      group had very close follow-up, and any additional improvement (if present) would
      be small and hard to detect. ClinicalTrials.gov identifier: NCT00624260.

PMID- 29365059
TI  - Response to "Why the Micromort Concept Falls Short in Breast Implant-Associated
      Anaplastic Large Cell Lymphoma (BIA-ALCL) Risk Analysis".

PMID- 29365060
TI  - Next-generation immunotherapies for lymphoma: one foot in the future.
AB  - Improved understanding of the interactions between cancer cells and the immune
      system combined with technological advances has led to the development of novel
      types of immunotherapies. These include checkpoint inhibitors, T-cell engager
      antibodies and chimeric antigen receptor T cells which have demonstrated
      remarkable efficacy in B-cell malignancies, including anti-PD1 antibodies in
      Hodgkin lymphoma, and T-cell engager antibodies and chimeric antigen receptor T
      cells in B-cell acute lymphoblastic leukemia, leading to their approval in these
      indications. Recent clinical data suggest that these immunotherapies may also
      benefit patients with other types of hematologic malignancies, particularly
      patients with Hodgkin and non-Hodgkin lymphomas. Here, we review the most recent
      clinical data regarding these different immunotherapies in patients with
      lymphoma. Ongoing and future studies should further define which immunotherapy
      may best apply to a given patient in order to provide a 'personalized
      immunotherapy'.

PMID- 29365061
TI  - Nanofat Grafting for Scar Treatment and Skin Quality Improvement.
AB  - Background: Fat grafting has been gaining attention in tissue augmentation over
      the past decade, not only for lipofilling, but also for its observed regenerative
      properties and overall skin texture improvement. Objectives: The aim of this
      study was to analyze the effect of nanofat grafting on scars, wrinkles, and skin
      discolorations in our clinic. Methods: Nanofat was prepared by a standard
      emulsification and filtration protocol. The resulting liquid was injected
      intradermally or directly into the scar tissue. Skin quality was evaluated based
      on a scoring system, and patient satisfaction was documented. Three physicians
      compared and analyzed standardized pre- and posttreatment photographs in respect
      to general improvement of skin aesthetics. Results: Fifty-two patients were
      treated with nanofat from November 2013 to April 2016. The mean (+/- standard
      deviation) posttreatment follow up was 155 +/- 49 days and average volume of
      harvested fat amounted to 165 cc. The primary harvesting areas were the abdomen
      and flanks, and the injected volume of nanofat ranged from 1 to 25 mL (mean, 4.6
      mL). A total of 40 scars (76% of all patient defects) were effectively treated as
      well as 6 patients with wrinkles, and 6 patients with discoloration.
      Posttreatment clinical evaluations showed a marked improvement of scar quality
      and a high patient satisfaction. The results in our clinic showed that nanofat
      grafting softened the scars, made discolorations less pronounced, and wrinkles
      appeared less prominent. Conclusions: Nanofat grafting has been shown to have
      beneficial effects in the treatment of scars, wrinkles, and skin discolorations.
      Level of Evidence 4: 

PMID- 29365062
TI  - Social relationships in physicians' work moderate relationship between workload
      and wellbeing-9-year follow-up study.
AB  - Background: Increasing wellbeing problems among physicians may lead to serious
      consequences in health care and means to prevent such development are called for.
      This study examined longitudinal associations between workload and changes in
      distress, sleep quality and workability in physicians and whether positive social
      relations at work would protect from such problems. Methods: A baseline survey
      was conducted in 2006 for a random sample of 5000 physicians (n = 2841, response
      rate 57%). In 2015, the follow-up survey was sent to those 2 206 physicians who
      gave their consent (n = 1462, response rate 68.3%). The survey included scales
      for distress, sleeping problems, workability, workload, team climate, collegial
      support and questions for background information. Results: Increased workload was
      associated with increased psychological distress, sleeping problems and decreased
      workability during the 9-year follow-up. Good team climate and collegial support
      were related to decreased distress and sleep quality and enhanced workability.
      Good collegial support buffered the associations of workload changes on distress
      and sleep quality changes. Team climate was more strongly associated with changes
      in sleep quality and workability among younger and middle aged physicians than
      older physicians. Also collegial support had a stronger association with sleep
      quality change among younger or middle aged physicians than older physicians.
      These associations were robust to adjustments for age, gender, specialization,
      leadership position, marital status and baseline wellbeing. Conclusions: Health
      care organizations should take measures to decrease workload and to increase
      availability of social support for physicians in order to protect physicians from
      declining wellbeing.

PMID- 29365064
TI  - Prepectoral Revision Breast Reconstruction for Treatment of Implant-Associated
      Animation Deformity: A Review of 102 Reconstructions.
AB  - Background: Animation deformity is a direct consequence of subpectoral implant
      placement for breast reconstruction following mastectomy. Current treatment
      options ameliorate but do not address the source of the problem. Moving the
      implant from subpectoral to prepectoral has the potential to eliminate animation
      deformity. Objectives: Describe the technique and outcomes of prepectoral
      revision reconstruction in over 100 cases and discuss patient selection criteria
      for a successful outcome. Methods: Patients who presented with animation
      deformity following two-stage implant reconstruction were included in this
      retrospective study. Revision surgery involved removal of the existing implant
      via the previous incision site along the inframammary fold, suturing of the
      pectoralis major muscle back to the chest wall, creation of a prepectoral pocket
      for the new implant, use of acellular dermal matrix to reinforce the prepectoral
      pocket and completely cover the implant, and fat grafting to enhance soft tissue.
      Patients were evaluated for resolution of animation deformity and occurrence of
      complications during follow up. Results: Fifty-seven patients (102 breasts)
      underwent prepectoral revision reconstruction with complete resolution of
      animation deformity. Complications occurred in 4 breasts (3.9%) and included
      seroma (2 breasts), skin necrosis (3 breasts), and wound dehiscence (1 breast).
      All 4 breasts with complications had their implants removed and replaced. There
      were no incidences of infection or clinically significant capsular contracture in
      this series. Conclusions: Revision reconstruction with prepectoral implant
      placement and complete coverage with acellular dermal matrix resolves animation
      deformity and results in aesthetically pleasing soft breasts. Patient selection
      is critical for the success of this technique. Level of Evidence 4: 

PMID- 29365065
TI  - Does biventricular conversion bring survival benefits to patients with an
      unbalanced atrioventricular septal defect?

PMID- 29365063
TI  - De novo mutations in GRIN1 cause extensive bilateral polymicrogyria.
AB  - Polymicrogyria is a malformation of cortical development. The aetiology of
      polymicrogyria remains poorly understood. Using whole-exome sequencing we found
      de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios
      with polymicrogyria. We found nine further de novo missense GRIN1 mutations in
      additional cortical malformation patients. Shared features in the patients were
      extensive bilateral polymicrogyria associated with severe developmental delay,
      postnatal microcephaly, cortical visual impairment and intractable epilepsy.
      GRIN1 encodes GluN1, the essential subunit of the N-methyl-d-aspartate receptor.
      The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region
      (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These
      regions are rarely mutated in the normal population or in GRIN1 patients without
      polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we
      showed that the polymicrogyria-associated GRIN1 mutations significantly alter the
      in vitro activity of the receptor. Three of the mutations increased agonist
      potency while one reduced proton inhibition of the receptor. These results are
      striking because previous GRIN1 mutations have generally caused loss of function,
      and because N-methyl-d-aspartate receptor agonists have been used for many years
      to generate animal models of polymicrogyria. Overall, our results expand the
      phenotypic spectrum associated with GRIN1 mutations and highlight the important
      role of N-methyl-d-aspartate receptor signalling in the pathogenesis of
      polymicrogyria.

PMID- 29365067
TI  - Impairment of Validity of Comparison Between Short-Course and Prolonged-Course
      Antibiotic Therapy Using Propensity Score Matching.

PMID- 29365068
TI  - Genetic transformation of cell-walled plant and algae cells: delivering DNA
      through the cell wall.
AB  - Transformation techniques are a fundamental tool for functional genomics studies.
      These techniques are routinely used in many prokaryotic and eukaryotic organisms,
      but in eukaryotes that are surrounded by a cell wall, these protocols have proven
      difficult to successfully deliver heterologous or homologous DNA within their
      cytoplasm and nucleus. Such cell-walled organisms represent a challenge that
      requires the development of genetic transformation techniques that are able to
      overcome their natural barrier, to achieve targeted gene expression. Here, we
      review the techniques that have been proven successful and applied to these cell
      walled eukaryotic organisms. We focus, especially, on plant cells, microalgae,
      and the latest approaches to mediate DNA uptake by the photosynthetic
      dinoflagellate Symbiodinium.

PMID- 29365069
TI  - Management of expanding aortic arch aneurysm after hybrid endovascular and
      debranching repair.
AB  - Hybrid procedures are used to treat aneurysms of the transverse aortic arch
      (TAA), combining debranching of the brachiocephalic vessels with endovascular
      approaches. Continued enlargement of the aneurysmal sac is a late complication. A
      60-year-old man presented with an expanding transverse aortic arch aneurysm after
      prior hybrid repair and underwent left posterolateral thoracotomy, partial
      excision of the previous stent graft and replacement with an interposition graft.

PMID- 29365070
TI  - Encoding of Auditory Temporal Gestalt in the Human Brain.
AB  - The perception of an acoustic rhythm is invariant to the absolute temporal
      intervals constituting a sound sequence. It is unknown where in the brain
      temporal Gestalt, the percept emerging from the relative temporal proximity
      between acoustic events, is encoded. Two different relative temporal patterns,
      each induced by three experimental conditions with different absolute temporal
      patterns as sensory basis, were presented to participants. A linear support
      vector machine classifier was trained to differentiate activation patterns in
      functional magnetic resonance imaging data to the 2 different percepts. Across
      the sensory constituents the classifier decoded which percept was perceived. A
      searchlight analysis localized activation patterns specific to the temporal
      Gestalt bilaterally to the temporoparietal junction, including the planum
      temporale and supramarginal gyrus, and unilaterally to the right inferior frontal
      gyrus (pars opercularis). We show that auditory areas not only process absolute
      temporal intervals, but also integrate them into percepts of Gestalt and that
      encoding of these percepts persists in high-level associative areas. The findings
      complement existing knowledge regarding the processing of absolute temporal
      patterns to the processing of relative temporal patterns relevant to the
      sequential binding of perceptual elements into Gestalt.

PMID- 29365071
TI  - Trends in prescribing of non-steroidal anti-inflammatory drugs in patients with
      cardiovascular disease: influence of national guidelines in UK primary care.
AB  - Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to
      treat pain, but have potential side effects in patients with cardiovascular
      disease (CVD). Objectives: To determine trends in NSAIDs prescribing between 2002
      and 2010 in patients with CVD, and ascertain whether prescribing patterns changed
      following publication of major national (the Medicines and Healthcare products
      Regulatory Agency (MHRA) and the National Institute for Health and Clinical
      Excellence (NICE)) guidance to GPs. Methods: This was an observational database
      study of adult patients in 11 practices (Staffordshire, England). NSAIDs were
      categorised into basic, COX-2 and topical. Study duration was divided on a
      quarterly basis from 2002-quarter-1 to 2010q4. CVD patients were identified using
      pre-defined Read Codes recorded in the two years prior to each quarter. Quarterly
      prevalence was determined. Times of significant changes in prescribing trends
      were determined using Joinpoint Regression, and compared to dates of the five
      major guidelines (in 2004q4, 2005q1, 2005q3, 2006q4, 2008q1). Results: In CVD
      patients, the prescription of basic NSAIDs showed a decreasing trend throughout
      the study period, from 774 (95% CI, 691-863) per 10000 patients in 2002q1 to 245
      (204-291) in 2010q4. COX-2 prescribing increased from 232/10000 (187-286) in
      2002q1 to 403/10000 (348-464) in 2004q3. Prescribing then fell sharply to
      102/10000 (76-134) in 2005q2 before stabilising around 55/10000. Topical NSAIDs
      prescribing showed a steady increase, starting at 115/10000 (108-123) in 2002q1
      and ending at 270/10000 (258-281) in 2010q4. Similar trends were observed in
      patients without CVD, particularly a sharp drop in COX-2 prescribing also
      occurred from 2004q4 when initial MHRA guidance was issued. Conclusion: Despite
      guidelines and a trend toward decreased prescribing, the use of potentially
      harmful NSAIDs continued in CVD patients. The MHRA directives potentially might
      have affected patients without CVD who may have inappropriately restricted their
      use of COX-2.

PMID- 29365072
TI  - Outcomes of a total cavopulmonary connection in patients with impaired
      ventricular function.
AB  - OBJECTIVES: Our aim was to evaluate outcomes following a total cavopulmonary
      connection (TCPC) in patients with preoperatively impaired ventricular function
      (VF). METHODS: Of 483 consecutive TCPC patients, 44 (9.1%) had impaired VF
      (ejection fraction <50%, Group A), and 439 patients had normal VF (ejection
      fraction >=50%, Group B). We compared the clinical outcomes between the groups.
      RESULTS: The median age at TCPC was 2.8 (interquartile range 1.9-8.3) years in
      Group A and 2.3 (1.8-3.5) years in Group B (P = 0.025). An atrioventricular valve
      (AVV) operation prior to (38.6 vs 27.1%, P < 0.001) and concomitant with (31.8 vs
      12.1%, P < 0.001) the TCPC was performed more frequently in Group A. The median
      intensive care unit stay (7.0 vs 7.0 days, P = 0.737) and 30-day survival (97.7
      vs 98.4%, P = 0.737) were not significantly different between groups. Freedom
      from death, transplantation (P = 0.115) and catheter intervention (P = 0.603)
      showed no difference between groups. However, freedom from cardiac reoperation
      was significantly lower in Group A (P < 0.001). VF was resolved in 22 of the 39
      (56.4%) survivors in Group A. The recovered patients had a lower incidence of AVV
      reoperation (0 vs 6, P = 0.002) and pacemaker rhythm (0 vs 5, P = 0.006).
      CONCLUSIONS: In patients planned for TCPC, impaired VF is often associated with
      AVV regurgitation. TCPC can be performed with low risk and comparable clinical
      results except for cardiac reoperation in patients with impaired VF when compared
      to patients with normal VF. Following TCPC, VF recovers in half of the survivors.
      A competent AVV and sinus rhythm are prerequisites for recovery.

PMID- 29365066
TI  - Structural brain abnormalities in the common epilepsies assessed in a worldwide
      ENIGMA study.
AB  - Progressive functional decline in the epilepsies is largely unexplained. We
      formed the ENIGMA-Epilepsy consortium to understand factors that influence brain
      measures in epilepsy, pooling data from 24 research centres in 14 countries
      across Europe, North and South America, Asia, and Australia. Structural brain
      measures were extracted from MRI brain scans across 2149 individuals with
      epilepsy, divided into four epilepsy subgroups including idiopathic generalized
      epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis
      (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n =
      1026), and compared to 1727 matched healthy controls. We ranked brain structures
      in order of greatest differences between patients and controls, by meta-analysing
      effect sizes across 16 subcortical and 68 cortical brain regions. We also tested
      effects of duration of disease, age at onset, and age-by-diagnosis interactions
      on structural measures. We observed widespread patterns of altered subcortical
      volume and reduced cortical grey matter thickness. Compared to controls, all
      epilepsy groups showed lower volume in the right thalamus (Cohen's d = -0.24 to 
      0.73; P < 1.49 * 10-4), and lower thickness in the precentral gyri bilaterally (d
      = -0.34 to -0.52; P < 4.31 * 10-6). Both MTLE subgroups showed profound volume
      reduction in the ipsilateral hippocampus (d = -1.73 to -1.91, P < 1.4 * 10-19),
      and lower thickness in extrahippocampal cortical regions, including the
      precentral and paracentral gyri, compared to controls (d = -0.36 to -0.52; P <
      1.49 * 10-4). Thickness differences of the ipsilateral temporopolar,
      parahippocampal, entorhinal, and fusiform gyri, contralateral pars triangularis,
      and bilateral precuneus, superior frontal and caudal middle frontal gyri were
      observed in left, but not right, MTLE (d = -0.29 to -0.54; P < 1.49 * 10-4).
      Contrastingly, thickness differences of the ipsilateral pars opercularis, and
      contralateral transverse temporal gyrus, were observed in right, but not left,
      MTLE (d = -0.27 to -0.51; P < 1.49 * 10-4). Lower subcortical volume and cortical
      thickness associated with a longer duration of epilepsy in the all-epilepsies,
      all-other-epilepsies, and right MTLE groups (beta, b < -0.0018; P < 1.49 * 10-4).
      In the largest neuroimaging study of epilepsy to date, we provide information on
      the common epilepsies that could not be realistically acquired in any other way.
      Our study provides a robust ranking of brain measures that can be further
      targeted for study in genetic and neuropathological studies. This worldwide
      initiative identifies patterns of shared grey matter reduction across epilepsy
      syndromes, and distinctive abnormalities between epilepsy syndromes, which inform
      our understanding of epilepsy as a network disorder, and indicate that certain
      epilepsy syndromes involve more widespread structural compromise than previously
      assumed.

PMID- 29365073
TI  - Primary safety results from the LEADLESS Observational Study.
AB  - Aims: A prospective, single-arm, multicentre, post-market study was conducted to
      confirm the short-term safety of the NanostimTM leadless pacemaker (LP). In this
      study, we report the primary results of the LEADLESS Observational Study. Methods
      and results: Subjects meeting VVIR pacemaker indications were enrolled and
      followed up after successful LP implantation, prior to discharge and post
      implantation at 90 days, 180 days, and every 6 months thereafter for the
      assessment of adverse events. The primary safety endpoint was evaluated in terms
      of freedom from serious adverse device effects (SADEs) at 6 months in 300
      subjects. Data for all enrolled subjects were also presented. A total of 470
      subjects were enrolled (75.8 +/- 13.1 years, 62.8% male). The study paused in
      April 2014 following the occurrence of perforation events that led to changes in
      the protocol and investigator training. Freedom from SADEs, evaluated in 300
      subjects enrolled post-pause, was 94.6% (95% confidence interval 91.0-97.2%) and
      demonstrated non-inferiority to a performance goal of 86% (P < 0.0001). Eighteen
      SADEs were observed in 16 (5.3%) subjects. The most frequently occurring events
      were cardiac perforation (1.3%), device dislodgement (0.3%), and vascular
      complications (1.3%). In the 470 subjects, 34 similar SADEs were observed in 31
      (6.6%) subjects. After stratifying the results in relation to the study pause,
      there was a statistically significant difference in the final LP location (septum
      vs. apex) (P < 0.0001) and the number of repositioning attempts (<2 vs. >=2) (P =
      0.05) and a decreasing trend in the rates of cardiac perforation and device
      dislodgement. Conclusion: The primary safety endpoint at 6 months was
      successfully met for the Nanostim LP. The occurrence of cardiac perforation and
      device dislodgement declined after changes following the study pause.

PMID- 29365074
TI  - A successful permanent pacemaker implantation in a challenging case with giant
      heart.

PMID- 29365075
TI  - Reply to Al-Hasan et al.

PMID- 29365076
TI  - Precision of CAPILLARYS 2 for the Detection of Hemoglobin Variants Based on Their
      Migration Positions.
AB  - Objectives: In this report, we evaluated utility of the capillary electrophoresis
      (CE) migration position of the CAPILLARYS 2 CE instrument. Methods: The precision
      of this x-axis number was determined on a selection of common hemoglobin (Hb)
      variants (Hb S, Hb C, Hb D-Punjab, Hb E, Hb Hope), and the reproducibility of
      this number was evaluated by comparing the results obtained by two large
      reference laboratories on 81 Hb variants. Additionally, the CE migration position
      is given for a total of 409 Hb variants. Results: The x-axis migration position
      showed excellent intra- and interassay precision. Comparison of Hb variants seen
      by both laboratories showed that 83% had a difference in migration position of 1
      unit or less. Only three rare Hb variants showed a difference of more than 2
      units. Conclusion: In summary, the CE migration position is a reproducible value
      and can be used as an aid in the identification of Hb variants.

PMID- 29365077
TI  - Programmed electrical stimulation-guided encircling cryoablation concomitant to
      surgical ventricular reconstruction for primary prevention of ventricular
      arrhythmias.
AB  - OBJECTIVES: Surgical ventricular reconstruction (SVR) is an effective treatment
      to improve left ventricular (LV) function in patients with ischaemic heart
      failure and an LV anterior-apical aneurysm. Ventricular arrhythmia (VA) is an
      important cause for morbidity and mortality in these patients. Therefore,
      encircling cryoablation targeting the VA substrate may be required. Programmed
      electrical stimulation (PES) can identify patients at risk for VA. The objective
      of this study was to evaluate the incidence and type of VA during long-term
      follow-up after PES-guided encircling cryoablation concomitant to SVR for primary
      prevention of VA. METHODS: Thirty-eight patients without spontaneous VA referred
      for SVR who underwent preoperative PES were included (PES group); 27 (71%)
      patients inducible for aneurysm-related VA received cryoablation. A historical
      cohort of 39 patients without spontaneous VA, preoperative PES and antiarrhythmic
      surgery served as the control group. Patients were discharged with an implantable
      cardioverter defibrillator (ICD). RESULTS: During 74 +/- 35 months of follow-up,
      no arrhythmic deaths occurred. Five-year survival for the total study population
      was 78%. Twenty-eight (36%) patients experienced >=1 VA. There were no
      differences in the number and type of ICD therapies between groups: shocks, P =
      0.699 and antitachypacing, P = 0.403. Five-year VA-free survival was 61% for the
      PES group and 65% for the control group (hazard ratio 1.67, P = 0.290).
      CONCLUSIONS: The majority of the patients referred for SVR without previously
      documented VA was inducible for aneurysm-related VA. During the follow-up, more
      than one-third of the patients experienced sustained VA and 25% received
      appropriate ICD therapy. No difference in VA occurrence or ICD therapy was
      observed between groups.

PMID- 29365078
TI  - Neural Evidence for the Contribution of Active Suppression During Working Memory
      Filtering.
AB  - In order to efficiently process incoming visual information, selective attention
      acts as a filter that enhances relevant and suppresses irrelevant information. In
      this study, we used an event-related potential (ERP) approach with systematic
      lateralization to investigate enhancement and suppression during encoding of
      information into visual working memory (WM) separately. We used a change
      detection task in which observers had to memorize some items while ignoring other
      items. We found that the to-be-ignored items elicited a PD component in the ERP,
      suggesting that irrelevant information is actively suppressed from WM. The PD
      amplitude increased with distractor load and decreased with the ability to group
      distractors according to Gestalt principles. This suggests that the PD can be
      used as an indicator of how efficiently items can be suppressed from entering WM.
      Furthermore, while lateral memory-targets elicited a "traditional" CDA (starting
      ~300 ms), lateral memory-distractors elicited a sustained positivity
      contralateral to memory-distractors (CDAp, starting ~400 ms). In sum the results
      suggest that inhibition of irrelevant information is an important factor for
      efficient WM and is reflected in spontaneous (PD) and sustained suppression
      (CDAp).

PMID- 29365079
TI  - Endogenous Sonic Hedgehog limits inflammation and angiogenesis in the ischaemic
      skeletal muscle of mice.
AB  - Aims: Hedgehog (Hh) signalling has been shown to be re-activated in ischaemic
      tissues and participate in ischaemia-induced angiogenesis. Sonic Hedgehog (Shh)
      is upregulated by more than 80-fold in the ischaemic skeletal muscle, however its
      specific role in ischaemia-induced angiogenesis has not yet been fully
      investigated. The purpose of the present study was to investigate the role of
      endogenous Shh in ischaemia-induced angiogenesis. Methods and results: To this
      aim, we used inducible Shh knock-out (KO) mice and unexpectedly found that
      capillary density was significantly increased in re-generating muscle of Shh
      deficient mice 5 days after hind limb ischaemia was induced, demonstrating that
      endogenous Shh does not promote angiogenesis but more likely limits it. Myosin
      and MyoD expression were equivalent in Shh deficient mice and control mice,
      indicating that endogenous Shh is not required for ischaemia-induced myogenesis.
      Additionally, we observed a significant increase in macrophage infiltration in
      the ischaemic muscle of Shh deficient mice. Our data indicate that this was due
      to an increase in chemokine expression by myoblasts in the setting of impaired Hh
      signalling, using tissue specific Smoothened conditional KO mice. The increased
      macrophage infiltration in mice deficient for Hh signalling in myocytes was
      associated with increased VEGFA expression and a transiently increased
      angiogenesis, demonstrating that Shh limits inflammation and angiogenesis
      indirectly by signalling to myocytes. Conclusion: Although ectopic administration
      of Shh has previously been shown to promote ischaemia-induced angiogenesis, the
      present study reveals that endogenous Shh does not promote ischaemia-induced
      angiogenesis. On the contrary, the absence of Shh leads to aberrant ischaemic
      tissue inflammation and a transiently increased angiogenesis.

PMID- 29365080
TI  - Identification of cardiac long non-coding RNA profile in human dilated
      cardiomyopathy.
AB  - Aims: Dilated cardiomyopathy (DCM) induced chronic heart failure is a life
      threatening disease worldwide. Long non-coding RNAs (lncRNAs) are potential new
      therapeutic targets and may provide new pathophysiological mechanisms for
      development of DCM. Methods and results: Microarray assays in 14 DCM and 10
      control human heart samples identified 313 significantly differentially expressed
      lncRNAs. SiRNAs were used to explore the potential function of specific lncRNAs
      (RP11-544D21.2 and XLOC_014288) in human cardiac myocytes, human cardiac
      fibroblasts and human cardiac microvascular endothelial cells, respectively. RNA
      seq and pathway analyses revealed the function of lncRNA RP11-544D21.2 and
      XLOC_014288 in three heart cells. Furthermore, impaired tube formation and
      migration were observed in si-RP11-544D21.2-treated endothelial cells. Moreover,
      TAF10 was predicted and verified to be one of the causes of some up-regulated
      lncRNAs. Then, we found that the left ventricular ejection fraction correlated
      with these changed lncRNAs. Conclusions: This study provides a comparison of
      human cardiac lncRNA profiles in control and DCM. It illustrates the function and
      complex roles of the differentially expressed lncRNAs in different cell types in
      the heart, which may lead to new insights into the mechanisms and treatment
      strategies for DCM in the future.

PMID- 29365081
TI  - Neonatal Hypoxia-Ischemia Causes Functional Circuit Changes in Subplate Neurons.
AB  - Neonatal hypoxia-ischemia (HI) in the preterm human results in damage to
      subcortical developing white matter and cognitive impairments. Subplate neurons
      (SPNs) are among the first-born cortical neurons and are necessary for normal
      cerebral development. While moderate or severe HI at P1 in rats leads to SPN
      loss, it is unclear if HI, esp. forms not associated with overt cell loss lead to
      altered SPN circuits. Thus, we used two HI models with different severities in P1
      rats. Cauterization of the common carotid artery (CCA) causes a largely transient
      and thus milder ischemia (HI-Caut) while CCA ligation causes more severe ischemia
      (HI-Lig). While HI-Lig caused subplate damage, HI-Caut did not cause overt
      histological damage on the light microscopic level. We used laser-scanning
      photostimulation (LSPS) in acute thalamocortical slices of auditory cortex during
      P5-10 to study the functional connectivity of SPNs. Both HI categories resulted
      in hyperconnectivity of excitatory and inhibitory circuits to SPNs. Thus,
      alterations on the circuit level are present in the absence of cell loss. Our
      results show that SPN circuits are uniquely susceptible to HI. Given the key
      developmental role of SPNs, our results suggest that altered SPN circuits might
      underlie the abnormal development of cortical function after HI.

PMID- 29365082
TI  - Early microbial colonization affects DNA methylation of genes related to
      intestinal immunity and metabolism in preterm pigs.
AB  - Epigenetic regulation may play an important role in mediating microbe-host
      interactions and adaptation of intestinal gene expression to bacterial
      colonization just after birth. This is particularly important after preterm birth
      because the immature intestine is hypersensitive to invading bacteria. We
      compared the intestinal DNA methylome and microbiome between conventional (CON)
      and antibiotics-treated (AB) preterm pigs, used as a model for preterm infants.
      Oral AB treatment reduced bacterial density (~100-fold), diversity and
      fermentation, improved the resistance to necrotizing enterocolitis (NEC) and
      changed the genome-wide DNA methylation in the distal small intestine.
      Integration of epigenome data with previously obtained proteome data showed that
      intestinal immune-metabolic pathways were affected by the AB-induced delay in
      bacterial colonization. DNA methylation and expression of intestinal genes,
      related to innate immune response, phagocytosis, endothelial homeostasis and
      tissue metabolism (e.g. CPN1, C3, LBP, HIF1A, MicroRNA-126, PTPRE), differed
      between AB and CON pigs even before any evidence of NEC lesions. Our findings
      document that the newborn immature intestine is influenced by bacterial
      colonization via DNA methylation changes. Microbiota-dependent epigenetic
      programming of genes related to gut immunity, vascular integrity and metabolism
      may be critical for short- and long-term intestinal health in preterm neonates.

PMID- 29365084
TI  - An integrative view of cell cycle control in Escherichia coli.
AB  - Bacterial proliferation depends on the cells' capability to proceed through
      consecutive rounds of the cell cycle. The cell cycle consists of a series of
      events during which cells grow, copy their genome, partition the duplicated DNA
      into different cell halves and, ultimately, divide to produce two newly formed
      daughter cells. Cell cycle control is of the utmost importance to maintain the
      correct order of events and safeguard the integrity of the cell and its genomic
      information. This review covers insights into the regulation of individual key
      cell cycle events in Escherichia coli. The control of initiation of DNA
      replication, chromosome segregation and cell division is discussed. Furthermore,
      we highlight connections between these processes. Although detailed mechanistic
      insight into these connections is largely still emerging, it is clear that the
      different processes of the bacterial cell cycle are coordinated to one another.
      This careful coordination of events ensures that every daughter cell ends up with
      one complete and intact copy of the genome, which is vital for bacterial
      survival.

PMID- 29365085
TI  - Blood pressure variability and risk of cardiovascular events and death in
      patients with hypertension and different baseline risks.
AB  - Aims: Blood pressure variability is associated with increased risk of
      cardiovascular events, particularly in high-risk patients. We assessed if
      variability was associated with increased risk of cardiovascular events and death
      in hypertensive patients at different risk levels. Methods and results: The
      Valsartan Antihypertensive Long-term Use Evaluation trial was a randomized
      controlled trial of valsartan vs. amlodipine in patients with hypertension and
      different risks of cardiovascular events, followed for a mean of 4.2 years. We
      calculated standard deviation (SD) of mean systolic blood pressure from visits
      from 6 months onward in patients with >=3 visits and no events during the first 6
      months. We compared the risk of cardiovascular events in the highest and lowest
      quintile of visit-to-visit blood pressure variability, using Cox regression. For
      analysis of death, variability was analysed as a continuous variable. Of 13 803
      patients included, 1557 (11.3%) had a cardiovascular event and 1089 (7.9%) died.
      Patients in the highest quintile of SD had an increased risk of cardiovascular
      events [hazard ratio (HR) 2.1, 95% confidence interval (95% CI) 1.7-2.4; P <
      0.0001], and a 5 mmHg increase in SD of systolic blood pressure was associated
      with a 10% increase in the risk of death (HR 1.10, 95% CI 1.04-1.17; P = 0.002).
      Associations were stronger among younger patients and patients with lower
      systolic blood pressure, and similar between patients with different baseline
      risks, except for higher risk of death among patients with established
      cardiovascular disease. Conclusion: Higher visit-to-visit systolic blood pressure
      variability is associated with increased risk of cardiovascular events in
      patients with hypertension, irrespective of baseline risk of cardiovascular
      events. Associations were stronger in younger patients and in those with lower
      mean systolic blood pressure.

PMID- 29365087
TI  - Duration of Antimicrobial Therapy for Enterobacteriaceae Bacteremia: Using
      Convenient End Points for Convenient Conclusions.

PMID- 29365083
TI  - As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral
      Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited
      Settings: A5264/AMC-067 Randomized Clinical Trial.
AB  - Background: Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds
      to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We
      assessed the impact of immediate vs as-needed oral etoposide (ET) among human
      immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS
      initiating ART. Methods: Chemotherapy-naive, HIV type 1-infected adults with mild
      to-moderate KS initiating ART in Africa and South America were randomized to ART
      (tenofovir/emtricitabine/efavirenz) alone (chemotherapy "as-needed" arm) vs ART
      plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression
      on ART alone received ET as part of the as-needed strategy. Primary outcome was
      ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes
      included time to initial KS progression, KS-associated immune reconstitution
      inflammatory syndrome (KS-IRIS), and KS response. Results: Of 190 randomized
      participants (as-needed = 94, immediate = 96), the majority were men (71%) and
      African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response
      (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those
      with week 48 data potential (N = 163, P = .91). Time to KS progression (P =
      .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm.
      Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell
      changes, and HIV RNA suppression were similar at 48 weeks. Conclusions: Among HIV
      infected adults with mild-to-moderate KS, immediate ET provided early, nondurable
      clinical benefits. By 48 weeks, no clinical benefit was observed compared to use
      of ET as needed. Mortality was high and tumor response was low. Clinical Trials
      Registration: NCT01352117.

PMID- 29365086
TI  - Genetic landscape of ultra-stable chronic lymphocytic leukemia patients.
AB  - Background: Chronic lymphocytic leukemia (CLL) has a heterogeneous clinical
      course. Beside patients requiring immediate treatment, others show an initial
      indolent phase followed by progression and others do not progress for decades.
      The latter two subgroups usually display mutated IGHV genes and a favorable FISH
      profile. Patients and methods: Patients with absence of disease progression for
      over 10 years (10-34) from diagnosis were defined as ultra-stable CLL (US-CLL).
      Forty US-CLL underwent extensive characterization including whole exome
      sequencing (WES), ultra-deep sequencing and copy number aberration (CNA) analysis
      to define their unexplored genetic landscape. Microarray analysis, comparing US
      CLL with non-US-CLL with similar immunogenetic features (mutated IGHV/favorable
      FISH), was also carried out to recognize US-CLL at diagnosis. Results: WES was
      carried out in 20 US-CLL and 84 non-silent somatic mutations in 78 genes were
      found. When re-tested in a validation cohort of 20 further US-CLL, no recurrent
      lesion was identified. No clonal mutations of NOTCH1, BIRC3, SF3B1 and TP53 were
      found, including ATM and other potential progression driving mutations. CNA
      analysis identified 31 lesions, none with known poor prognostic impact. No novel
      recurrent lesion was identified: most cases showed no lesions (38%) or an
      isolated del(13q) (31%). The expression of 6 genes, selected from a gene
      expression profile analysis by microarray and quantified by droplet digital PCR
      on a cohort of 79 CLL (58 US-CLL and 21 non-US-CLL), allowed to build a decision
      tree capable of recognizing at diagnosis US-CLL patients. Conclusions: The
      genetic landscape of US-CLL is characterized by the absence of known unfavorable
      driver mutations/CNA and of novel recurrent genetic lesions. Among CLL patients
      with favorable immunogenetics, a decision-tree based on the expression of 6 genes
      may identify at diagnosis patients who are likely to maintain an indolent disease
      for decades.

PMID- 29365088
TI  - Reply to Buratto et al.

PMID- 29365089
TI  - Stat5-dependent cardioprotection in late remote ischaemia preconditioning.
AB  - Aims: To study the protective effects of late remote ischaemic preconditioning
      (RIPC) against myocardial ischaemia/reperfusion (I/R) injury and determine
      whether Stat5 is involved in this protection by using cardiomyocyte-specific
      Stat5 knockout mice (Stat5-cKO). Methods and results: Mice were exposed to lower
      limb RIPC or sham ischaemia. After 24 h, the left anterior descending artery
      (LAD) was ligated for 30 min, then reperfused for 180 min. The myocardial infarct
      size (IS), apoptotic rate of cardiomyocytes, and serum myocardial enzymes were
      measured to evaluate for cardioprotective effects. Heart tissues were harvested
      to determine the cardiomyocytes' anti-apoptotic and survival signaling. When
      compared with the Stat5fl/fl mice without RIPC, Stat5fl/fl mice with RIPC
      (Stat5fl/fl+RIPC + I/R) displayed a decreased myocardial IS/LV (16 +/- 1.5 vs.
      30.1 +/- 3.1%, P < 0.01; IS/ area at risk (AAR), 42.2 +/- 3.5 vs. 69.2 +/- 4.9%,
      P < 0.01), a reduced cardiomyocyte apoptotic rate (2.1 +/- 0.37 vs. 5.5 +/-
      0.53%, P < 0.01), and lower creatine kinase (CK), lactate dehydrogenase (LDH),
      and creatine kinase-MB (CK-MB) levels. To the contrary, the Stat5-cKO mice
      (Stat5fl/fl; Tnnt2Cremice with Doxycycline treatment for 7 days) did not exhibit
      any effect of RIPC-induced cardioprotection. Activation of STAT5 protein was
      significantly higher in the Stat5fl/fl+RIPC + I/R group than in the
      Stat5fl/fl+I/R group, while there was no significant difference between the Stat5
      cKO + RIPC + I/R and the Stat5-cKO + I/R group. Further analyses with heart
      tissues detected decreased protein expressions of cytochrome c (Cyt c) and
      cleaved Caspase-3 in the Stat5fl/fl+RIPC + I/R mice, along with increased anti
      apoptotic molecules, including B-cell lymphoma-extra large (Bcl-xL) and B-cell
      lymphoma-2 (Bcl-2); such changes were not noted in the Stat5-cKO + RIPC + I/R
      mice. Additionally, RIPC increased cardiac hypoxia inducible factor-1 (HIF
      1alpha) and interleukin-10 (IL10) protein levels and caused activation of AKT,
      phosphatidylinositol 3 kinase (PI3K), and vascular endothelial growth factor in
      the heart of the Stat5fl/fl mice. However, these changes were completely
      inhibited by the absence of Stat5. Conclusions: These results suggest that RIPC
      induced late cardioprotection against myocardial I/R injury is Stat5-dependent
      and is correlated with the activation of anti-apoptotic signaling and
      cardiomyocyte-survival signaling.

PMID- 29365090
TI  - Long-term results of pulmonary valve annular enlargement with valve repair in
      tetralogy of Fallot.
AB  - OBJECTIVES: We adopted an operative technique of pulmonary valve (PV) annular
      enlargement with valve repair in tetralogy of Fallot (TOF) correction to reduce
      postoperative pulmonary regurgitation (PR) 16 years ago. Here, we have evaluated
      the long-term results. METHODS: Between April 2000 and August 2005, 43 patients
      (26 men) with tetralogy of Fallot with pulmonary stenosis underwent PV annular
      enlargement with valve repair. The median age and body weight at the time of
      surgery were 14 months and 10.2 kg, respectively. RESULTS: There was no operative
      mortality. Mean postoperative PR grade at discharge was 0.93 +/- 0.40 (none or
      trivial in 10 patients, mild in 27 patients, mild to moderate in 5 patients and
      moderate in 1 patient), and the mean postoperative pressure gradient across PV
      was 13.0 +/- 10.9 mmHg. The mean follow-up duration was 131.9 +/- 42.9 months.
      During follow-up, 1 reoperation was performed for residual ventricular septal
      defect. The mean PR grade at the last follow-up echocardiography was 1.59 +/-
      0.60 (mild in 17 patients, mild to moderate in 8 patients, moderate in 14
      patients, moderate to severe in 1 patient and severe in 3 patients), and the mean
      pressure gradient was 22.7 +/- 9.9 mmHg. We have compared the incidence of
      moderate or more PR with the incidence of patients who underwent simple
      transannular patch enlargement through propensity score matching. The PV repair
      group had a lower incidence of moderate or more PR compared with the simple
      transannular patch group (40% vs 68%, P = 0.04). CONCLUSIONS: PV annular
      enlargement with valve repair has reasonable long-term results and yields a lower
      long-term incidence of significant PR compared with the simple transannular patch
      enlargement technique.

PMID- 29365091
TI  - NMR metabolomic signatures reveal predictive plasma metabolites associated with
      long-term risk of developing breast cancer.
AB  - Background: Combination of metabolomics and epidemiological approaches opens new
      perspectives for ground-breaking discoveries. The aim of the present study was to
      investigate for the first time whether plasma untargeted metabolomic profiles,
      established from a simple blood draw from healthy women, could contribute to
      predict the risk of developing breast cancer within the following decade and to
      better understand the aetiology of this complex disease. Methods: A prospective
      nested case-control study was set up in the Supplementation en Vitamines et
      Mineraux Antioxydants (SU.VI.MAX) cohort, including 206 breast cancer cases
      diagnosed during a 13-year follow-up and 396 matched controls. Untargeted nuclear
      magnetic resonance (NMR) metabolomic profiles were established from baseline
      plasma samples. Multivariable conditional logistic regression models were
      computed for each individual NMR variable and for combinations of variables
      derived by principal component analysis. Results: Several metabolomic variables
      from 1D NMR spectroscopy were associated with breast cancer risk. Women
      characterized by higher fasting plasma levels of valine, lysine, arginine,
      glutamine, creatine, creatinine and glucose, and lower plasma levels of
      lipoproteins, lipids, glycoproteins, acetone, glycerol-derived compounds and
      unsaturated lipids had a higher risk of developing breast cancer. P-values ranged
      from 0.00007 [odds ratio (OR)T3vsT1=0.37 (0.23-0.61) for glycerol-derived
      compounds] to 0.04 [ORT3vsT1=1.61 (1.02-2.55) for glutamine]. Conclusion: This
      study highlighted associations between baseline NMR plasma metabolomic signatures
      and long-term breast cancer risk. These results provide interesting insights to
      better understand complex mechanisms involved in breast carcinogenesis and evoke
      plasma metabolic disorders favourable for carcinogenesis initiation. This study
      may contribute to develop screening strategies for the identification of at-risk
      women for breast cancer well before symptoms appear.

PMID- 29365092
TI  - The influence of advanced age on venous-arterial extracorporeal membrane
      oxygenation outcomes.
AB  - OBJECTIVES: Ethical and health care economic concerns surround the use of venous
      arterial extracorporeal membrane oxygenation (VA-ECMO) in elderly patients.
      Patients requiring VA-ECMO are often in critical condition and the decision to
      cannulate is time-sensitive. We investigated the relationship between age and VA
      ECMO outcomes to better inform this decision. METHODS: This is a retrospective
      study of 355 patients placed on VA-ECMO between March 2007 and August 2016 at our
      institution. Using piecewise modelling, age became associated with in-hospital
      mortality after 63 years. Based on further analysis with the chi2 statistic
      maximization, patients were divided into 2 age groups: <=72 years old [Group Y
      (Young), n = 310] and >72 years old [Group O (Old), n = 45]. Multivariable
      logistic regression was performed to identify preoperative predictors of in
      hospital mortality. RESULTS: Patients over the age of 72 had a significantly
      higher prevalence of comorbidities, including coronary disease, previous strokes
      and chronic kidney disease. Weaning from ECMO was achieved in 76% of Group Y and
      47% of Group O (P < 0.001). In-hospital mortality was 52% among Group Y and 69%
      among Group O (P = 0.037). Multivariable logistic regression using preoperative
      risk factors identified coronary artery disease, acute decompensated heart
      failure and an age >72 years as independent predictors of mortality (age >72
      years: odds ratio 2.71, 95% confidence interval 1.22-6.00; P = 0.01).
      CONCLUSIONS: VA-ECMO in-hospital mortality is considerable across all age groups.
      However, age only becomes associated with mortality after 63 years and rises
      dramatically after 72 years. This study provides useful insight into these time
      sensitive decisions for the development of possible practice guidelines.

PMID- 29365093
TI  - Ketamine intervention limits pathogen expansion in vitro.
AB  - Ketamine is one of several clinically important drugs whose therapeutic efficacy
      is due in part to their ability to act upon ion channels prevalent in nearly all
      biological systems. In studying eukaryotic and prokaryotic organisms in vitro, we
      show that ketamine short-circuits the growth and spatial expansion of three
      microorganisms, Stachybotrys chartarum, Staphylococcus epidermidis and Borrelia
      burgdorferi, at doses efficient at reducing depression-like behaviors in mouse
      models of clinical depression. Although our findings do not reveal the
      mechanism(s) by which ketamine mediates its antifungal and antibacterial effects,
      we hypothesize that a function of L-glutamate signal transduction is associated
      with the ability of ketamine to limit pathogen expansion. In general, our
      findings illustrate the functional similarities between fungal, bacterial and
      human ion channels, and suggest that ketamine or its metabolites not only act in
      neurons, as previously thought, but also in microbial communities colonizing
      human body surfaces.

PMID- 29365095
TI  - An easy and efficient approach for testing identifiability.
AB  - Motivation: The feasibility of uniquely estimating parameters of dynamical
      systems from observations is a widely discussed aspect of mathematical modelling.
      Several approaches have been published for analyzing this so-called
      identifiability of model parameters. However, they are typically computationally
      demanding, difficult to perform and/or not applicable in many application
      settings. Results: Here, an approach is presented which enables quickly testing
      of parameter identifiability. Numerical optimization with a penalty in radial
      direction enforcing displacement of the parameters is used to check whether
      estimated parameters are unique, or whether the parameters can be altered without
      loss of agreement with the data indicating non-identifiability. This
      Identifiability-Test by Radial Penalization (ITRP) can be employed for every
      model where optimization-based parameter estimation like least-squares or maximum
      likelihood is feasible and is therefore applicable for all typical systems
      biology models. The approach is illustrated and tested using 11 ordinary
      differential equation (ODE) models. Availability and implementation: The
      presented approach can be implemented without great efforts in any modelling
      framework. It is available within the free Matlab-based modelling toolbox
      Data2Dynamics. Source code is available at https://github.com/Data2Dynamics.
      Contact: ckreutz@fdm.uni-freiburg.de. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 29365094
TI  - A multiplex lateral flow immunoassay for the rapid identification of NDM-, KPC-,
      IMP- and VIM-type and OXA-48-like carbapenemase-producing Enterobacteriaceae.
AB  - Objectives: The global spread of carbapenemase-producing Enterobacteriaceae
      represents a substantial challenge in clinical practice and rapid and reliable
      detection of these organisms is essential. The aim of this study was to develop
      and validate a lateral flow immunoassay (Carba5) for the detection of the five
      main carbapenemases (KPC-, NDM-, VIM- and IMP-type and OXA-48-like). Methods:
      Carba5 was retrospectively and prospectively evaluated using 296 enterobacterial
      isolates from agar culture. An isolated colony was suspended in extraction buffer
      and then loaded on the manufactured Carba5. Results: All 185 isolates expressing
      a carbapenemase related to one of the Carba5 targets were correctly and
      unambiguously detected in <15 min. All other isolates gave negative results
      except those producing OXA-163 and OXA-405, which are considered low-activity
      carbapenemases. No cross-reaction was observed with non-targeted carbapenemases,
      ESBLs, AmpCs or oxacillinases (OXA-1, -2, -9 and -10). Overall, this assay
      reached 100% sensitivity and 95.3% (retrospectively) to 100% (prospectively)
      specificity. Conclusions: Carba5 is efficient, rapid and easy to implement in the
      routine workflow of a clinical microbiology laboratory for confirmation of the
      five main carbapenemases encountered in Enterobacteriaceae.

PMID- 29365096
TI  - Immune neutralization of the receptor for advanced glycation end products reduce
      liver oxidative damage induced by an acute systemic injection of
      lipopolysaccharide.
AB  - The receptor for advanced glycation end products (RAGE) is a multi-ligand
      receptor, which activation amplifies and perpetuates inflammatory reactions. RAGE
      activation also strongly stimulates the production of reactive oxygen species,
      leading an imbalance of redox cellular state. The extent of liver damage caused
      by inflammation is crucial to the systemic response during proinflammatory
      episodes. To investigate the role of RAGE in liver damage caused by systemic
      inflammation, we evaluated the effect of RAGE blocking in oxidative stress
      parameters induced by systemic lipopolysaccharide (LPS) injection. Wistar rats
      received an intraperitoneal injection of RAGE antibody (50 mg/kg), 1 h prior
      intraperitoneal injection of LPS (5 mg/kg). Twenty-four hours later, the liver
      was isolated for analysis. The LPS-induced effect in protein oxidative damage,
      mitochondrial complex II activity, catalase activity, signal transducer and
      activator of transcription 3 phosphorylation and caspase 3 activation was
      prevented by prior treatment with RAGE antibody. However, RAGE blocking was not
      able to inhibit reactive oxygen species production and the impairment in non
      enzymatic antioxidant capacity induced by LPS. The present results indicate that
      RAGE is an important mediator of liver oxidative damage induced by an acute
      systemic injection of LPS, although other mechanisms may also be responsible for
      liver function impairment during inflammation.

PMID- 29365097
TI  - Impact in stability during sequential CDR grafting to construct camelid VHH
      antibodies against zinc oxide and gold.
AB  - Biomolecules which recognize inorganic materials and metal surfaces gain much
      attention for creating new type of nanomaterials and sensors. 4F2, a camelid VHH
      antibody, recognizes ZnO surface and has been applied for sensor applications.
      4F2 was constructed sequential complementarity determining region (CDR)
      replacement on the parental VHH antibody, termed the Construction of Antibody by
      Integrating Grafting and Evolution Technology; CAnIGET procedure. Here, we
      evaluate the influence of CDR replacements during 4F2 generation using
      calorimetric technique. We found that the initial peptide grafting at CDR1
      results in the stability reduction and subsequent CDR3 randomize and selection
      restore the stability during the construction of 4F2. Further examination using
      anti-gold VHH, AuE32, revealed that the final CDR3 randomize and selection step
      has little effect in stability while the initial CDR1 grafting reduces the
      stability as same as the case for 4F2. Our results showing here provide the
      detailed view of the stability alteration during the CAnIGET procedure.

PMID- 29365098
TI  - Safety of perioperative cerebral oxygen saturation during debranching in patients
      with incomplete circle of Willis.
AB  - OBJECTIVES: The consequences of common carotid artery (CCA) cross-clamping during
      debranching before thoracic endovascular aortic repair are unclear. We examined
      the safety of a simple CCA cross-clamping procedure under regional cerebral
      oxygen saturation monitoring (rSO2) in patients with a complete or incomplete
      circle of Willis (CoW) anatomy. METHODS: Twenty-eight patients with thoracic
      aneurysm underwent elective debranching thoracic endovascular aortic repair with
      bilateral frontal rSO2 monitoring at our institution between January 2012 and
      October 2015. Before CCA cross-clamping, we maintained a systemic mean arterial
      pressure of >100 mm Hg with a vasopressor. We recorded the bilateral frontal rSO2
      before, during and after CCA cross-clamping. RESULTS: The CoW was incomplete in
      11 (39.3%) patients. Of these, 6 patients had a complication of ischaemic
      potential. The left frontal rSO2 was <50% in 3 patients but did not fall below
      40%. Compared with baseline values (mean +/- SD 64.6 +/- 6.9%), the left frontal
      rSO2 showed no significant change perioperatively in those with a complete CoW on
      the left CCA cross-clamping (during: 61.0 +/- 7.9%, P = 0.17; after: 65.1 +/-
      5.9%, P = 0.09). In patients with an incomplete CoW with ischaemic potential, the
      left frontal rSO2 did not change significantly after cross-clamping (baseline:
      59.8 +/- 3.2%, during: 55.5 +/- 5.0%; P = 0.10) but increased significantly on
      declamping (62.8 +/- 4.5%, P = 0.023). The extent of the changes in the mean left
      frontal rSO2 on clamping and declamping decreased and increased by 7.3% and
      11.7%, respectively, in patients with an incomplete CoW, when compared with 5.3%
      and 5.8% in those with a complete CoW (P = 0.65 and 0.31, respectively). No
      perioperative cerebrovascular events were observed. CONCLUSIONS: Simple CCA cross
      clamping during debranching was safe when arterial pressure was supported and
      rSO2 was monitored, even with an incomplete CoW and ischaemic potential.

PMID- 29365099
TI  - Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to
      Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis.
AB  - Context: Treatment of postmenopausal osteoporosis with teriparatide parathyroid
      hormone amino terminal 1-34 increases bone formation and improves bone
      microarchitecture. A possible modulator of action is periostin. In vitro
      experiments have shown that periostin might regulate osteoblast differentiation
      and bone formation through Wnt signaling. The effect of teriparatide on periostin
      is not currently known. Objectives: To determine the effect of teriparatide
      treatment on circulating levels of periostin and other regulators of bone
      formation and investigate how changes in periostin relate to changes in bone
      turnover markers, regulators of bone formation, and bone mineral density (BMD).
      Participants and Design: Twenty women with osteoporosis; a 2-year open-label
      single-arm study. Intervention: Teriparatide 20 ug was administered by
      subcutaneous injection daily for 104 weeks. Periostin, sclerostin, and Dickkopf
      related protein 1, procollagen type I N-terminal propeptide (PINP), and C
      telopeptide of type I collagen were measured in fasting serum collected at
      baseline (two visits) and then at weeks 1, 2, 4, 12, 26, 52, 78, and 104. BMD was
      measured at the lumbar spine, total hip, and femoral neck using dual energy x-ray
      absorptiometry. Results: Periostin levels increased by 6.6% [95% confidence
      interval (CI), -0.4 to 13.5] after 26 weeks of teriparatide treatment and
      significantly by 12.5% (95% CI, 3.3 to 21.0; P < 0.01) after 52 weeks. The change
      in periostin correlated positively with the change in the lumbar spine BMD at
      week 52 (r = 0.567; 95% CI, 0.137 to 0.817; P < 0.05) and femoral neck BMD at
      week 104 (r = 0.682; 95% CI, 0.261 to 0.885; P < 0.01). Conclusions: Teriparatide
      therapy increases periostin secretion; it is unclear whether this increase
      mediates the effect of the drug on bone.

PMID- 29365100
TI  - Proteomic analysis of FOXP proteins reveals interactions between cortical
      transcription factors associated with neurodevelopmental disorders.
AB  - FOXP transcription factors play important roles in neurodevelopment, but little
      is known about how their transcriptional activity is regulated. FOXP proteins
      cooperatively regulate gene expression by forming homo- and hetero-dimers with
      each other. Physical associations with other transcription factors might also
      modulate the functions of FOXP proteins. However, few FOXP-interacting
      transcription factors have been identified so far. Therefore, we sought to
      discover additional transcription factors that interact with the brain-expressed
      FOXP proteins, FOXP1, FOXP2 and FOXP4, through affinity-purifications of protein
      complexes followed by mass spectrometry. We identified seven novel FOXP
      interacting transcription factors (NR2F1, NR2F2, SATB1, SATB2, SOX5, YY1 and
      ZMYM2), five of which have well-estabslished roles in cortical development.
      Accordingly, we found that these transcription factors are co-expressed with
      FoxP2 in the deep layers of the cerebral cortex and also in the Purkinje cells of
      the cerebellum, suggesting that they may cooperate with the FoxPs to regulate
      neural gene expression in vivo. Moreover, we demonstrated that etiological
      mutations of FOXP1 and FOXP2, known to cause neurodevelopmental disorders,
      severely disrupted the interactions with FOXP-interacting transcription factors.
      Additionally, we pinpointed specific regions within FOXP2 sequence involved in
      mediating these interactions. Thus, by expanding the FOXP interactome we have
      uncovered part of a broader neural transcription factor network involved in
      cortical development, providing novel molecular insights into the transcriptional
      architecture underlying brain development and neurodevelopmental disorders.

PMID- 29365101
TI  - Physiologically based pharmacokinetic modelling prediction of the effects of dose
      adjustment in drug-drug interactions between levonorgestrel contraceptive
      implants and efavirenz-based ART.
AB  - Background: HIV-positive women receiving efavirenz-based ART and levonorgestrel
      contraceptive implants are at risk of low levonorgestrel exposure and unintended
      pregnancy. Objectives: To investigate clinically applicable dose-adjustment
      strategies to overcome the known drug-drug interaction (DDI) between
      levonorgestrel and efavirenz, using a physiologically based pharmacokinetic
      (PBPK) modelling-based approach. Methods: A PBPK model was qualified against
      clinical data to predict levonorgestrel plasma concentrations when standard-dose
      (150 mg) levonorgestrel implants were administered alone (control group), as well
      as when standard-dose or increased-dose (300 mg) levonorgestrel implants were
      coadministered with either 600 or 400 mg of efavirenz. Results: No difference was
      seen between in vivo clinical and PBPK-model-simulated levonorgestrel plasma
      concentrations (P > 0.05). Simulated levonorgestrel plasma concentrations were
      ~50% lower at 48 weeks post-implant-placement in virtual individuals receiving
      standard-dose levonorgestrel with either 600 or 400 mg of efavirenz compared with
      the control group (efavirenz:control geometric mean ratio = 0.42 and 0.49,
      respectively). Conversely, increased-dose levonorgestrel in combination with
      either 600 or 400 mg of efavirenz was sufficient to restore levonorgestrel
      concentrations to levels similar to those observed in the 150 mg levonorgestrel
      control group 48 weeks post-implant-placement (efavirenz:control geometric mean
      ratio = 0.86 and 1.03, respectively). Conclusions: These results suggest that the
      clinically significant DDI between efavirenz and levonorgestrel is likely to
      persist despite efavirenz dose reduction, whereas dose escalation of implantable
      levonorgestrel may represent a successful clinical strategy to circumvent
      efavirenz-levonorgestrel DDIs and will be of use to inform clinical trial design
      to assess coadministration of efavirenz and levonorgestrel implants.

PMID- 29365103
TI  - Characterization of a yeast sporulation-specific P450 family protein, Dit2, using
      an in vitro assay to crosslink formyl tyrosine.
AB  - The outermost layer of the yeast Saccharomyces cerevisiae spore, termed the
      dityrosine layer, is primarily composed of bisformyl dityrosine. Bisformyl
      dityrosine is produced in the spore cytosol by crosslinking of two formyl
      tyrosine molecules, after which it is transported to the nascent spore wall and
      assembled into the dityrosine layer by an unknown mechanism. A P450 family
      protein, Dit2, is believed to mediate the crosslinking of bisformyl dityrosine
      molecules. To characterize Dit2 and gain insight into the biological process of
      dityrosine layer formation, we performed an in vitro assay to crosslink formyl
      tyrosine with using permeabilized cells. For an unknown reason, the production of
      bisformyl dityrosine could not be confirmed under our experimental conditions,
      but dityrosine was detected in acid hydrolysates of the reaction mixtures in a
      Dit2 dependent manner. Thus, Dit2 mediated the crosslinking of formyl tyrosine in
      vitro. Dityrosine was detected when formyl tyrosine, but not tyrosine, was used
      as a substrate and the reaction required NADPH as a cofactor. Intriguingly, apart
      from Dit2, we found that the spore wall, but not the vegetative cell wall,
      contains bisformyl dityrosine crosslinking activity. This activity may be
      involved in the assembly of the dityrosine layer.

PMID- 29365102
TI  - Falls and Hospitalizations Among Persons With Dementia and Associated Caregiver
      Emotional Difficulties.
AB  - Background and Objectives: Falls and hospitalizations are adverse health events
      commonly experienced by persons with dementia (PWDs). These events often require
      urgent care from a family caregiver and may increase caregiver stress. We examine
      falls and hospitalizations among PWDs as predictors of caregivers' reported care
      related emotional difficulty, in addition to care-related stressors. Research
      Design and Methods: Cross-sectional telephone survey of 652 informal caregivers
      for PWDs. A multinomial logistic regression examined falls (last month) and
      hospitalizations (prior year) experienced by PWDs as predictors of caregivers'
      care-related emotional difficulty, accounting for demographic characteristics and
      primary and secondary caregiving stressors. Results: Over 20% of caregivers
      reported high levels of care-related emotional difficulty. Controlling for
      demographic characteristics and primary and secondary caregiving stressors, the
      PWD's prior month fall was significantly associated with greater care-related
      emotional difficulty; the PWD's hospitalizations were not associated with care
      related emotional difficulty. Discussion and Implications: Approximately 30% of
      PWDs had experienced a past year hospitalization and prior month fall, and one in
      five caregivers reported high emotional difficulty related to care. Although
      secondary strains and resources of caregiving were strong predictors of care
      related emotional difficulty, PWDs' falls represent a significant stressor that
      increases odds of caregiver emotional difficulty over and above other strains.
      Consequently, a fall experienced by a PWD may represent a key time for clinicians
      to assess caregiver well-being.

PMID- 29365105
TI  - Three plural medical systems in East Asia: interpenetrative pluralism in China,
      exclusionary pluralism in Korea and subjugatory pluralism in Japan.
AB  - Amid persistent interest in and concerns about traditional, complementary and
      alternative medicine (TCAM) in low-, middle- and high-income countries, the
      global community of healthcare is in need of learning ways to institutionalize
      TCAM with biomedicine. By investigating how traditional East Asian medicine
      (TEAM), one of the most popular forms of TCAM in the world, is institutionalized
      in China, Korea and Japan, this study finds three different ways of instituting a
      plural medical system in which TCAM and biomedicine intersect with each other. In
      the interpenetrative pluralism in China and the exclusionary pluralism in Korea,
      TEAM and biomedicine are institutionalized as independent and equivalent systems
      of medical practices. However, TEAM and biomedicine are conditioned to cross over
      into each other unconditionally in practice in the former, whereas the two
      exclude each other very strictly in the latter. In the subjugatory pluralism in
      Japan, the crisscrossing of TEAM and biomedicine is allowed, yet in an
      asymmetrical way whereby the practice of TEAM is dependent upon and subordinated
      into biomedicine. The practice of various TEAM modalities is overseen by TEAM
      doctors, biomedicine doctors or integrative TEAM-biomedicine doctors in
      interpenetrative pluralism, by TEAM doctors only in exclusionary pluralism, and
      by biomedicine doctors only in subjugatory pluralism. These varying
      characteristics demonstrate a variety of plural medical systems. They also
      provide useful cues in accounting for the varying behaviours of medical service
      providers and users who encounter TCAM as well as biomedicine in their everyday
      practices. In addition, the growing literature about the outcomes of TCAM and
      plural medical systems can take advantage of these findings.

PMID- 29365104
TI  - Homozygous missense mutation L673P in adenylate kinase 7 (AK7) leads to primary
      male infertility and multiple morphological anomalies of the flagella but not to
      primary ciliary dyskinesia.
AB  - Motile cilia and sperm flagella share an extremely conserved microtubule-based
      cytoskeleton, called the axoneme, which sustains beating and motility of both
      organelles. Ultra-structural and/or functional defects of this axoneme are well
      known to cause primary ciliary dyskinesia (PCD), a disorder characterized by
      recurrent respiratory tract infections, chronic otitis media, situs inversus,
      male infertility and in most severe cases, hydrocephalus. Only recently,
      mutations in genes encoding axonemal proteins with preferential expression in the
      testis were identified in isolated male infertility; in those cases, individuals
      displayed severe asthenozoospermia due to Multiple Morphological Abnormalities of
      the sperm Flagella (MMAF) but not PCD features. In this study, we performed
      genetic investigation of two siblings presenting MMAF without any respiratory PCD
      features, and we report the identification of the c.2018T > G (p.Leu673Pro)
      transversion in AK7, encoding an adenylate kinase, expressed in ciliated tissues
      and testis. By performing transcript and protein analyses of biological samples
      from individual carrying the transversion, we demonstrate that this mutation
      leads to the loss of AK7 protein in sperm cells but not in respiratory ciliated
      cells, although both cell types carry the mutated transcript and no tissue
      specific isoforms were detected. This work therefore, supports the notion that
      proteins shared by both cilia and sperm flagella may have specific properties
      and/or function in each organelle, in line with the differences in their mode of
      assembly and organization. Overall, this work identifies a novel genetic cause of
      asthenozoospermia due to MMAF and suggests that in humans, more deleterious
      mutations of AK7 might induce PCD.

PMID- 29365107
TI  - CORRIGENDUM FOR "Identification of Novel Potentially Pleiotropic Variants
      Associated With Osteoporosis and Obesity Using the cFDR Method".

PMID- 29365108
TI  - Novel fast-track recovery protocol for alternative access transcatheter aortic
      valve replacement: application to non-femoral approaches.
AB  - OBJECTIVES: Although the transfemoral approach for transcatheter aortic valve
      replacement is the preferred choice, alternative access remains indicated for
      inadequate iliofemoral vessels. We report the successful implementation of a
      novel fast-track (FT) protocol for patients undergoing alternative access
      transcatheter aortic valve replacement compared with conventional controls.
      METHODS: Between September 2014 and January 2017, 31 and 23 patients underwent
      alternative access transcatheter aortic valve replacement under FT and pre-fast
      track (p-FT) protocols, respectively. Comparisons of outcomes (in terms of
      mortality, complications, readmissions and resource utilization) were made before
      and after the implantation of the FT protocol in September 2015. RESULTS:
      Overall, mean age was 78.7 years in FT and 79.6 years in p-FT patients (P =
      0.71). There were no significant differences in procedural (3.2% vs 13.0%, P =
      0.301) or 90-day mortality (3.2% vs 17.4%, P = 0.151) between the FT and p-FT
      groups, respectively. Compared with p-FT patients, FT patients had significantly
      shorter intensive care unit stays (12 h vs 27 h, P = 0.006) and a trend towards
      more discharges within 3 days (41.9% vs 17.4%, P = 0.081). Resource utilization
      analyses projected a 56% and 17% reduction in the mean intensive care unit time
      (hours) per 100 patients and the total length of stay (days) per 100 patients,
      respectively, with respect to the FT approach. CONCLUSIONS: This pilot study
      demonstrates the feasibility and safety of the novel FT protocol for alternative
      access transcatheter aortic valve replacement, resulting in shorter intensive
      care unit stays, without increasing procedural complications or readmissions.
      With the expected increase in transcatheter aortic valve replacement utilization,
      FT protocols should be integrated with a multidisciplinary heart team approach to
      enhance patient recovery and optimize resource utilization.

PMID- 29365109
TI  - Surgicel(r) packing remnants mimicking mediastinitis after adult cardiac surgery.
AB  - Surgicel(r) is one of the most commonly used bioabsorbable topical haemostatic
      agents. Some articles have reported that Surgicel(r) remnants might be
      misdiagnosed as an abscess. However, the number of reports in the cardiothoracic
      surgical field is limited. Herein, we report a 65-year-old woman who was
      suspected of having mediastinitis on computed tomography after redo-Bentall
      operation. Reoperation revealed that internal accumulation of Surgicel(r)
      remnants mimicked mediastinitis. It is important to share the use and location of
      Surgicel(r) with radiologists. If mediastinitis cannot be ruled out, the next
      step of reoperation or magnetic resonance imaging should be promptly taken.

PMID- 29365106
TI  - Psychosocial adversity and socioeconomic position during childhood and epigenetic
      age: analysis of two prospective cohort studies.
AB  - Psychosocial adversity in childhood (e.g. abuse) and low socioeconomic position
      (SEP) can have significant lasting effects on social and health outcomes. DNA
      methylation-based biomarkers are highly correlated with chronological age;
      departures of methylation-predicted age from chronological age can be used to
      define a measure of age acceleration, which may represent a potential biological
      mechanism linking environmental exposures to later health outcomes. Using data
      from two cohorts of women Avon Longitudinal Study of Parents and Children,
      (ALSPAC), N = 989 and MRC National Survey of Health and Development, NSHD, N =
      773), we assessed associations of SEP, psychosocial adversity in childhood
      (parental physical or mental illness or death, parental separation, parental
      absence, sub-optimal maternal bonding, sexual, emotional and physical abuse and
      neglect) and a cumulative score of these psychosocial adversity measures, with
      DNA methylation age acceleration in adulthood (measured in peripheral blood at
      mean chronological ages 29 and 47 in ALSPAC and buccal cells at age 53 in NSHD).
      Sexual abuse was strongly associated with age acceleration in ALSPAC (sexual
      abuse data were not available in NSHD), e.g. at the 47-year time point sexual
      abuse associated with a 3.41 years higher DNA methylation age (95% CI 1.53 to
      5.29) after adjusting for childhood and adulthood SEP. No associations were
      observed between low SEP, any other psychosocial adversity measure or the
      cumulative psychosocial adversity score and age acceleration. DNA methylation age
      acceleration is associated with sexual abuse, suggesting a potential mechanism
      linking sexual abuse with adverse outcomes. Replication studies with larger
      sample sizes are warranted.

PMID- 29365110
TI  - Steven Nissen MD.

PMID- 29365111
TI  - Handheld Echography devices: ready for prime time?

PMID- 29365112
TI  - What is CMR doing for patients today?

PMID- 29365113
TI  - A new Research Centre in Russia.

PMID- 29365114
TI  - A new Paediatric Centre in Russia.

PMID- 29365115
TI  - Frontiers in cardiac imaging: diagnostic and prognostic validity and safety.

PMID- 29365117
TI  - Progression of tremor in early stages of Parkinson's disease: a clinical and
      neuroimaging study.
AB  - Rest tremor is one of the cardinal signs of Parkinson's disease. Kinetic and
      postural tremors may also occur. The coexistence of these three types of tremor
      at disease onset and their subsequent progression could have important clinical
      and therapeutic implications but remain to be fully elucidated. We aimed to: (i)
      evaluate prevalence and progression of these three types of tremor in early
      stages of the disease; and (ii) investigate longitudinally the relationship
      between dopaminergic and serotonergic terminal dysfunction, rest tremor severity
      and its response to dopaminergic therapy. The Parkinson's Progressive Markers
      Initiative database provided the baseline and 2-year follow-up clinical ratings
      and 123ioflupane-fluoropropyl-carbomethoxy-3-beta-4-iodophenyltropane (123I-FP
      CIT) single photon emission computed tomography images for this study. 123I-FP
      CIT measured putamen dopamine transporter and median raphe serotonin transporter
      availability. A raphe/putamen uptake ratio was calculated for each patient as an
      index of relative involvement of these structures. Clinical analysis of tremor
      was conducted on 378 patients: 87.8% presented with tremor at baseline; rest
      tremor occurred in 69.6% of patients at baseline; and 67.9% at follow-up.
      Postural and kinetic tremors occurred in about 50% of patients at both baseline
      and follow-up. Over 20% of patients presenting with tremor did not exhibit a rest
      component at baseline. The number of patients with isolated rest tremor was
      halved at follow-up. In tremor predominant patients, rest tremor severity was
      inversely correlated with raphe serotonin transporter availability both at
      baseline and follow-up (baseline: constancy P < 0.05, tremor index P < 0.05;
      follow-up: amplitude P < 0.05, constancy P < 0.05, tremor index P < 0.05). In the
      entire cohort, more severe tremor scores correlated with lower raphe/putamen
      uptake ratio values, indicative of more severe raphe dysfunction (baseline:
      constancy P < 0.01, tremor index P < 0.05; follow-up: amplitude P < 0.01,
      constancy P < 0.001, tremor index P < 0.001). The percentage of improvement in
      rest tremor amplitude after acute dopaminergic therapy was smaller in patients
      with lower raphe/putamen uptake ratio values (P < 0.01). Rest tremor is the most
      represented type of tremor in early Parkinson's disease. However, postural and
      kinetic tremor can affect approximately half of these patients and can occur in
      absence of resting tremor. As disease progresses, both raphe serotonergic
      dysfunction and putamen dopamine depletion could contribute to the occurrence of
      rest tremor. The former is linked to more severe tremor scores and poorer
      response to dopaminergic therapy. Non-dopaminergic treatments might be beneficial
      for patients whose tremor is associated with a raphe-predominant dysfunction.

PMID- 29365116
TI  - Prepartum fatty acid supplementation in sheep. II. Supplementation of
      eicosapentaenoic acid and docosahexaenoic acid during late gestation alters the
      fatty acid profile of plasma, colostrum, milk and adipose tissue, and increases
      lipogenic gene expression of adipose tissue.
AB  - The objectives of this study were as follows: 1) to establish whether feeding a
      source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to ewes
      during late gestation changes the fatty acid profile of colostrum, milk, ewe
      adipose tissue, and plasma and subsequently lamb plasma and red blood cells
      (RBC), and 2) to investigate the effects of EPA and DHA on mRNA expression in ewe
      adipose tissue. Eighty-four gestating ewes (28 pens, three per pen) were blocked
      by lambing day and assigned to a diet with an addition of fat at 0.39% of the DM
      during the last 50 d of gestation using Ca salts of a palm fatty acid distillate
      (PFAD) high in palmitic and oleic acids or EPA + DHA. Blood samples were taken
      from ewes on days 20, 1 (parturition), and 30 and from lambs on days 1 and 30 for
      plasma fatty acid analysis. Fatty analysis of lamb RBC was performed on day 1.
      Colostrum samples were taken at lambing and milk samples on day 30 for fatty acid
      analysis. Subcutaneous adipose tissue biopsies were taken from one ewe per pen on
      day 20 for fatty acid analysis and gene expression analysis of 27 genes.
      Treatment * day interactions (P < 0.10) were observed for several isomers of
      C18:1, with concentrations that were greater in plasma of EPA + DHA ewes on day
      20, but were not different on day 1 or 30. Plasma concentrations of EPA tended to
      be greater (P = 0.07), whereas DHA was greater (P < 0.001) in EPA + DHA ewes
      compared with PFAD ewes. There was no difference in EPA or DHA in adipose tissue
      with EPA + DHA vs. PFAD supplementation (P > 0.10). Concentrations of fatty acids
      with 6 to 10 carbons were significantly increased (P < 0.05) in colostrum and
      milk of EPA + DHA ewes. There was a treatment * day interaction with EPA + DHA
      ewes yielding greater EPA (P = 0.03) and DHA (P = 0.04) concentrations than PFAD
      in colostrum, but not in milk. Treatment * day interactions (P < 0.05) were
      observed for several C18:1 isomers with concentrations that were greater in EPA +
      DHA ewe colostrum, but were not different between treatments in milk. In lamb
      plasma and RBC, EPA and DHA were not different between treatments (P > 0.10). The
      expression of fatty acid synthase and leptin was significantly increased (P <
      0.05), whereas the expression of diacylglycerol acyltransferase 2 tended to be
      increased (P = 0.08) by supplementation of EPA + DHA vs. PFAD. These results
      suggest that supplementation with EPA and DHA to ewes during late gestation
      alters the fatty acid profile of plasma, colostrum, and milk and may increase
      lipogenesis.

PMID- 29365118
TI  - Initial in vitro testing of a paediatric continuous-flow total artificial heart.
AB  - OBJECTIVES: Mechanical circulatory support has become standard therapy for adult
      patients with end-stage heart failure; however, in paediatric patients with
      congenital heart disease, the options for chronic mechanical circulatory support
      are limited to paracorporeal devices or off-label use of devices intended for
      implantation in adults. Congenital heart disease and cardiomyopathy often involve
      both the left and right ventricles; in such cases, heart transplantation, a
      biventricular assist device or a total artificial heart is needed to adequately
      sustain both pulmonary and systemic circulations. We aimed to evaluate the in
      vitro performance of the initial prototype of our paediatric continuous-flow
      total artificial heart. METHODS: The paediatric continuous-flow total artificial
      heart pump was downsized from the adult continuous-flow total artificial heart
      configuration by a scale factor of 0.70 (1/3 of total volume) to enable
      implantation in infants. System performance of this prototype was evaluated using
      the continuous-flow total artificial heart mock loop set to mimic paediatric
      circulation. We generated maps of pump performance and atrial pressure
      differences over a wide range of systemic vascular resistance/pulmonary vascular
      resistance and pump speeds. RESULTS: Performance data indicated left pump flow
      range of 0.4-4.7 l/min at 100 mmHg delta pressure. The left/right atrial pressure
      difference was maintained within +/-5 mmHg with systemic vascular
      resistance/pulmonary vascular resistance ratios between 1.4 and 35, with/without
      pump speed modulation, verifying expected passive self-regulation of atrial
      pressure balance. CONCLUSIONS: The paediatric continuous-flow total artificial
      heart prototype met design requirements for self-regulation and performance; in
      vivo pump performance studies are ongoing.

PMID- 29365119
TI  - Letter to the Editor: "Myonectin Predicts the Development of Type 2 Diabetes".

PMID- 29365120
TI  - Antibiotic resistance in Timor-Leste: a systematic review of evidence.

PMID- 29365121
TI  - New Tools for Old Questions: How Strictly Human Are "Human Schistosomes"-And Does
      It Matter?

PMID- 29365122
TI  - Rapid immunosurveillance by recirculating lymphocytes in the rat intestine:
      critical role of unsulfated sialyl-Lewis X on high endothelial venules of the
      Peyer's patches.
AB  - Naive lymphocytes systemically recirculate for immunosurveillance inspecting
      foreign antigens and pathogens in the body. Trafficking behavior such as the
      migration pathway and transit time within the gastrointestinal tract, however,
      remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred
      to a congeneic host that had undergone mesenteric lymphadenectomy. The migration
      pathway was investigated using newly developed four-color immunohistochemistry
      and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from
      which they emerged in mesenteric lymph around 4 h after intravenous injection.
      Immunohistochemistry showed that donor TDLs predominantly transmigrated across
      high endothelial venules (HEVs) at the interfollicular area of the Peyer's
      patches (PPs), then exited into the LYVE-1+ efferent lymphatics, that were close
      to the venules. The rapid recirculation depended largely on the local expression
      of unsulfated sialyl-Lewis X on these venules where putative dendritic cells
      (DCs) were associated underneath. Recruited naive T cells briefly made contact
      with resident DCs before exiting to the lymphatics in the steady state. In some
      transplant settings, however, the T cells retained contact with DCs and were
      sensitized and differentiated into activated T cells. In conclusion, we directly
      demonstrated that lymphocyte recirculation within the gut is a very rapid
      process. The interfollicular area of PPs functions as a strategically central
      site for rapid immunosurveillance where HEVs, efferent lymphatics and resident
      DCs converge. PPs can, however, generate alloreactive T cells, leading to
      exacerbation of graft-versus-host disease or gut allograft rejection.

PMID- 29365123
TI  - How far is mixed methods research in the field of health policy and systems in
      Africa? A scoping review.
AB  - Both the academic and the policy community are calling for wider application of
      mixed methods research, suggesting that combined use of quantitative and
      qualitative methods is most suitable to assess and understand the complexities of
      health interventions. In spite of recent growth in mixed methods studies, limited
      efforts have been directed towards appraising and synthetizing to what extent and
      how mixed methods have been applied specifically to Health Policy and Systems
      Research (HPSR) in low- and middle-income countries (LMICs). We aimed at filling
      this gap in knowledge, by exploring the scope and quality of mixed methods
      research in the African context. We conducted a scoping review applying the
      framework developed by Arksey and O'Malley and modified by Levac et al. to
      identify and extract data from relevant studies published between 1950 and 2013.
      We limited our search to peer-reviewed HPSR publications in English, which
      combined at least one qualitative and one quantitative method and focused on
      Africa. Among the 105 studies that were retained for data extraction, over 60%
      were published after 2010. Nearly 50% of all studies addressed topics relevant to
      Health Systems, while Health Policy and Health Outcomes studies accounted
      respectively for 40% and 10% of all publications. The quality of the application
      of mixed methods varied greatly across studies, with a relatively small
      proportion of studies stating clearly defined research questions and
      differentiating quantitative and qualitative elements, including sample sizes and
      analytical approaches. The methodological weaknesses observed could be linked to
      the paucity of specific training opportunities available to people interested in
      applying mixed methods to HPSR in LMICs as well as to the limitations on word
      limit, scope and peer-review processes at the journals levels. Increasing
      training opportunities and enhancing journal flexibility may result in more and
      better quality mixed methods publications.

PMID- 29365124
TI  - Effects of high condensed-tannin substrate, prior dietary tannin exposure,
      antimicrobial inclusion, and animal species on fermentation parameters following
      a 48 h in vitro incubation.
AB  - Condensed tannins (CT), prior dietary CT exposure, animal species, and
      antimicrobial inclusion effects on 48 h extent of in vitro fermentation were
      measured in an experiment with a 3 * 2 * 2 * 3 factorial arrangement of
      treatments. Treatments included species of inoculum donor (Bos taurus, Ovis
      aries, or Capra hircus; n = 3/species), prior adaptation to dietary CT (not
      adapted or adapted), culture substrate (low-CT or high-CT), and antimicrobial
      additive (none, bacterial suppression with penicillin + streptomycin, or fungal
      suppression with cycloheximide). Low-CT or high-CT substrates were incubated in
      vitro using inoculum from animals either not exposed (period 1) or previously
      exposed to dietary CT (period 2). The extent of IVDMD after 48 h of incubation
      was greater (P < 0.001) for cultures with low-CT substrate (21.5%) than for
      cultures with high-CT substrate (16.5%). Cultures with high-CT substrate or with
      suppressed bacterial activity had less (P < 0.001) gas pressure than cultures
      with low-CT substrate or cultures with suppressed fungal activity. Total VFA
      concentrations were greater (P < 0.001) in low-CT cultures when inoculum donors
      were without prior CT exposure (83.7 mM) than when inoculum was from CT-exposed
      animals (79.6 mM). Conversely, total VFA concentrations were greater (P < 0.001)
      in high-CT cultures with tannin-exposed inoculum (59.4 mM) than with nonexposed
      inoculum (52.6 mM). As expected, CT and suppression of bacterial fermentative
      activities had strong negative effects on fermentation; however, prior exposure
      to dietary CT attenuated some negative effects of dietary CT on fermentation. In
      our experiment, the magnitude of inoculum-donor species effects on fermentation
      was minor.

PMID- 29365126
TI  - CORRIGENDUM FOR "The Role of Episodic Postprandial Peptides in Exercise-Induced
      Compensatory Eating".

PMID- 29365127
TI  - Genome scan identifies flowering-independent effects of barley HsDry2.2 locus on
      yield traits under water deficit.
AB  - Increasing crop productivity under conditions of climate change requires the
      identification, selection, and utilization of novel alleles for breeding. In this
      study, we analysed the genotype and field phenotype of the barley HEB-25 multi
      parent mapping population under well-watered and water-limited environments for
      two years. A genome-wide association study (GWAS) for genotype * environment
      interactions was performed for 10 traits including flowering time (heading time,
      HEA) and plant grain yield (PGY). Comparison of the GWAS for traits per se (i.e.
      regardless of the environment) with a study for quantitative trait loci (QTLs) *
      environment interactions (Q*E), indicates the prevalence of Q*E mostly for
      reproductive traits. One Q*E locus on chromosome 2, Hordeum spontaneum Dry2.2
      (HsDry2.2), showed a positive and conditional effect on PGY and grain number
      (GN). The wild allele significantly reduced HEA; however, this earliness was not
      conditioned by water deficit. Furthermore, BC2F1 lines segregating for the
      HsDry2.2 locus showed that the wild allele conferred an advantage over the
      cultivated allele in PGY, GN, and harvest index, as well as modified shoot
      morphology, a longer grain-filling period, and reduced senescence (only under
      drought). This suggests the presence of an adaptation mechanism against water
      deficit rather than an escape mechanism. The study highlights the value of
      evaluating wild relatives in search of novel alleles and provides clues to
      resilience mechanisms underlying crop adaptations to abiotic stress.

PMID- 29365128
TI  - Surveillance for Tick-Borne Viruses Near the Location of a Fatal Human Case of
      Bourbon Virus (Family Orthomyxoviridae: Genus Thogotovirus) in Eastern Kansas,
      2015.
AB  - Bourbon virus (Family Orthomyxoviridae: Genus Thogotovirus) was first isolated
      from a human case-patient residing in Bourbon County, Kansas, who subsequently
      died. Before becoming ill in late spring of 2014, the patient reported several
      tick bites. In response, we initiated tick surveillance in Bourbon County and
      adjacent southern Linn County during spring and summer of 2015. We collected
      20,639 host-seeking ticks representing four species from 12 sites. Amblyomma
      americanum (L.) (Acari: Ixodidae) and Dermacentor variabilis (Say) (Acari:
      Ixodidae) accounted for nearly all ticks collected (99.99%). Three tick pools,
      all composed of adult A. americanum ticks collected in Bourbon County, were virus
      positive. Two pools were Heartland virus (Family Bunyaviridae: Genus Phlebovirus)
      positive, and one was Bourbon virus positive. The Bourbon virus positive tick
      pool was composed of five adult females collected on a private recreational
      property on June 5. Detection of Bourbon virus in the abundant and aggressive
      human-biting tick A. americanum in Bourbon County supports the contention that A.
      americanum is a vector of Bourbon virus to humans. The current data combined with
      virus detections in Missouri suggest that Bourbon virus is transmitted to humans
      by A. americanum ticks, including both the nymphal and adult stages, that ticks
      of this species become infected as either larvae, nymphs or both, perhaps by
      feeding on viremic vertebrate hosts, by cofeeding with infected ticks, or both,
      and that Bourbon virus is transstadially transmitted. Multiple detections of
      Heartland virus and Bourbon virus in A. americanum ticks suggest that these
      viruses share important components of their transmission cycles.

PMID- 29365129
TI  - Delayed pollination and low availability of assimilates are major factors causing
      maize kernel abortion.
AB  - Selective seed abortion is a survival strategy adopted by many species that
      sacrifices some seeds to allow the remaining ones to set. While in evolutionary
      terms this is a successful approach, it causes huge losses to crop yields. A
      pollination time gap (PTG) has been suggested to be associated with position
      related grain abortion. To test this hypothesis, we developed a novel approach to
      alter the natural pattern of maize (Zea mays L.) pollination and to examine the
      impact of PTGs on kernel growth and the underlying physiological basis. When
      apical and basal kernels were synchronously pollinated, the basal kernels set and
      matured but the apical kernels were aborted at an early stage. Delaying
      pollination to the basal ovaries suppressed their development and reduced
      invertase activity and sugar levels, which allowed the apical kernels to set and
      grow normally. In situ localization revealed normal cell wall invertase activity
      in apical and basal kernels under synchronous pollination but reduced activity in
      the delayed-pollinated kernels independent of their position. Starch, which was
      abundant in basal kernel areas, was absent in the apical kernel regions under
      synchronous pollination but apparent with delayed pollination. Our analyses
      identified PTG-related sink strength and a low level of local assimilates as the
      main causes of grain abortion.

PMID- 29365131
TI  - A Downside to Hepatitis C Virus Cure? Vigilance Is Needed Regarding Hepatitis B
      Virus Reactivation, Organ Rejection, or Hepatocellular Carcinoma Progression.
AB  - Cure of hepatitis C virus has become feasible in almost all patients. However,
      vigilance is needed in 3 scenarios: previous exposure to hepatitis B virus (HBV),
      history of organ transplantation, and history of cured hepatocellular carcinoma
      (HCC). The current data suggest that HBV reactivation occurs in about 10% of
      hepatitis B surface antigen (HBsAg)-positive patients and approximately 1% of
      hepatitis B core antibody-positive but HBsAg-negative patients. The risk of organ
      rejection is also around 1%, but can be fatal if not acted on immediately.
      Finally, the risk of early HCC recurrence may be increased but should not delay
      initiation of antiviral therapy in the setting of cured HCC; however, increased
      surveillance may be warranted.

PMID- 29365130
TI  - Prevalence and Geographic Distribution of Borrelia miyamotoi in Host-Seeking
      Ixodes pacificus (Acari: Ixodidae) Nymphs in Mendocino County, California.
AB  - Borrelia miyamotoi is an increasingly recognized human pathogen transmitted by
      Ixodes ticks in the Northern Hemisphere. In North America, infection prevalences
      of B. miyamotoi are characteristically low (<10%) in Ixodes scapularis (Say;
      Acari: Ixodidae) and Ixodes pacificus (Cooley & Kohls; Acari: Ixodidae), both of
      which readily bite humans. We tested 3,255 host-seeking I. pacificus nymphs
      collected in 2004 from 79 sites throughout Mendocino County in north-coastal
      California for presence of B. miyamotoi. The collection sites represented a
      variety of forest types ranging from hot, dry oak woodlands in the southeast, to
      coastal redwoods in the west, and Ponderosa pine and Douglas fir-dominated areas
      in the northern part of the county. We found that B. miyamotoi was geographically
      widespread, but infected I. pacificus nymphs infrequently (cumulative prevalence
      of 1.4%). Infection prevalence was not significantly associated with geographic
      region or woodland type, and neither density of host-seeking nymphs, nor
      infection with Borrelia burgdorferi sensu stricto was associated with B.
      miyamotoi infection status in individual ticks. Because B. burgdorferi prevalence
      at the same sites was previously associated with woodland type and nymphal
      density, our results suggest that despite sharing a common vector, the primary
      modes of enzootic maintenance for the two pathogens are likely different.

PMID- 29365125
TI  - Decreased darunavir concentrations during once-daily co-administration with
      maraviroc and raltegravir: OPTIPRIM-ANRS 147 trial.
AB  - Background: The OPTIPRIM-ANRS 147 trial compared intensive combination ART
      (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir
      and maraviroc) started early during primary HIV-1 infection with standard
      tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and
      emtricitabine. From month 6 to 18, the percentage of viral load values <50
      copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we
      compared antiretroviral drug concentrations between the two arms. Methods: Plasma
      samples were collected from 50 patients at various times after drug
      administration. A Bayesian approach based on published population pharmacokinetic
      models was used to estimate residual drug concentrations (Ctrough) and exposures
      (AUC) in each patient. A mixed linear regression model was then used to compare
      the AUC and Ctrough values of each drug used in both groups. Results: Published
      models adequately described our data and could be used to predict Ctrough and
      AUC. No significant difference in tenofovir disoproxil fumarate, emtricitabine
      and ritonavir parameters was found between the two arms. However, darunavir
      Ctrough and AUC were significantly lower in the pentatherapy arm than in the
      tritherapy arm (P = 0.03 and P = 0.04, respectively). Conclusions: Adding
      maraviroc and raltegravir to darunavir-based tritherapy decreased darunavir
      concentrations. Compliance issues, maraviroc-darunavir interaction and
      raltegravir-darunavir interaction were suspected and may affect the kinetics of
      viral decay during pentatherapy. A specific pharmacokinetic interaction study is
      needed to explore the interactions between darunavir and maraviroc and
      raltegravir.

PMID- 29365133
TI  - Periprocedural myocardial infarction and injury in elective coronary stenting.
AB  - Aims: To assess the incidence, risk factors and prognosis of periprocedural
      myocardial infarction (MI) and myocardial injury in patients undergoing elective
      percutaneous coronary intervention (PCI). Methods and results: We included all
      consecutive patients who underwent elective PCI with a negative troponin level at
      admission from 1 January 2014 to 31 December 2015. The primary endpoint was
      defined as the composite of periprocedural MI (Type 4a MI), stent thrombosis
      (Type 4b MI), and myocardial injury according to the Third universal definition
      of MI. Multivariable analysis was performed to identify independent predictors of
      periprocedural MI and myocardial injury and its relation to 30-day and 1-year
      clinical outcome. Of the 1390 elective PCI patients, the primary endpoint
      occurred in 28.7% of patients, including 7.0% of Type 4a MI, 0.14% of Type 4b MI,
      and 21.6% of myocardial injury. Independent risk factors for the occurrence of
      the primary endpoint were left main PCI, total stent length >30 mm, multiple
      stenting, chronic kidney disease (estimated glomerular filtration rate <60
      mL/min) and age >75 years. At 30 days, patients with periprocedural MI and
      myocardial injury had a higher rate of cardiovascular events [5.5% vs. 1.2%,
      adjusted hazard ratio (adjHR) = 3.8, 95% confidence interval (CI) 1.9-6.9; P <
      0.001] mainly driven by ischaemic events (3.2% vs. 0.6%, HR 5.9, 95% CI 2.9-20; P
      < 0.0001). At 1-year, the risk of ischemic events remained higher in the
      periprocedural MI and myocardial injury group (adjHR = 1.7, 95% CI 1.1-2.6; P =
      0.004). Conclusions: Periprocedural MI and injury are frequent complications of
      elective PCI associated with an increased rate of cardiovascular events at 30
      days and 1 year.

PMID- 29365132
TI  - Transcriptional stimulation of rate-limiting components of the autophagic pathway
      improves plant fitness.
AB  - Autophagy is a major catabolic process whereby autophagosomes deliver cytoplasmic
      content to the lytic compartment for recycling. Autophagosome formation requires
      two ubiquitin-like systems conjugating Atg12 with Atg5, and Atg8 with lipid
      phosphatidylethanolamine (PE), respectively. Genetic suppression of these systems
      causes autophagy-deficient phenotypes with reduced fitness and longevity. We show
      that Atg5 and the E1-like enzyme, Atg7, are rate-limiting components of Atg8-PE
      conjugation in Arabidopsis. Overexpression of ATG5 or ATG7 stimulates Atg8
      lipidation, autophagosome formation, and autophagic flux. It also induces
      transcriptional changes opposite to those observed in atg5 and atg7 mutants,
      favoring stress resistance and growth. As a result, ATG5- or ATG7-overexpressing
      plants exhibit increased resistance to necrotrophic pathogens and oxidative
      stress, delayed aging and enhanced growth, seed set, and seed oil content. This
      work provides an experimental paradigm and mechanistic insight into genetic
      stimulation of autophagy in planta and shows its efficiency for improving plant
      productivity.

PMID- 29365134
TI  - Effects of Mosquito Control Adulticides on Sterile Cochliomyia hominivorax
      (Diptera: Calliphoridae).
AB  - Effects of mosquito control adulticides on sterile screwworm flies, Cochliomyia
      hominivorax (Coquerel) (Diptera: Calliphoridae), were investigated via bottle
      bioassays, outdoor cage tests, and exposure to treated vegetation. In bottle
      bioassays, 43 MUg of permethrin via dilution of Evoluer, 474.56 MUg of malathion
      via dilution of Fyfanon, and 25 MUg of naled via dilution of Dibrom Concentrate
      were used to challenge screwworm flies. Permethrin was more toxic to screwworm
      flies than was malathion, which was more toxic than naled. On succeeding days,
      permethrin was still lethal to the flies, whereas malathion and naled were less
      toxic. During outdoor cage trials, screwworm mortality declined as distance from
      the spray truck increased. Sterile screwworm flies were killed by lower
      concentrations of permethrin needed to kill black salt marsh mosquitoes, Aedes
      taeniorhynchus (Wiedemann) (Diptera: Culicidae). Flies exposed to treated
      vegetation taken from the path of the spray cloud died more quickly than did
      flies exposed to leaves taken 5 ft inside the canopy. Fly mortality increased as
      volume mean diameter of droplets increased. In spite of the toxicity of Evoluer
      to screwworm flies, aspects of their biology make it unlikely that mosquito
      control operations would affect released flies.

PMID- 29365135
TI  - Comparative Assessment of Four Steinernematidae and Three Heterorhabditidae
      Species for Infectivity of Larval Diabrotica Virgifera Virgifera.
AB  - Larval Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) were
      exposed to seven different entomopathogenic nematode species to test their
      potential infectivity in a laboratory setting. Known D. virgifera-infecting
      nematode species Heterorhabditis bacteriophora Poinar, Heterorhabditis megidis
      Poinar, Jackson & Klein, Steinernema feltiae Filipjev, and Steinernema
      carpocapsae Weiser were tested in a concerted experiment alongside Steinernema
      diaprepesi Nguyen & Duncan, Steinernema riobrave Cabanillas, Poinar & Raulston,
      and a Missouri wild-type H. bacteriophora which have not been previously tested
      on D. virgifera. The species S. rarum Doucet was tested separately for D.
      virgifera infectivity. Third-instar D. virgifera were exposed to either 60 or 120
      nematodes per larva for 6 d. Following exposure, mortality was recorded and
      larvae were examined to determine the presence of active nematode infections.
      Results indicated a significantly higher proportion of larvae with active
      infections from the Heterorhabditidae species and S. diaprepesi than the other
      Steinernematidae species for both exposure rates; mortality data indicated a
      similar trend. Steinernema rarum showed almost no infectivity in laboratory
      experiments.

PMID- 29365136
TI  - Overexpression of miR164b-resistant OsNAC2 improves plant architecture and grain
      yield in rice.
AB  - Plant architecture is a major target of rice (Oryza sativa) breeding and
      selection, but the underlying regulatory networks remain unclear. Here, we
      overexpressed an OsNAC2 mutant (OErN) that cannot be cleaved by the miRNA
      miR164b. OErN plants had better plant architecture and longer panicles, and
      produced more grains. The parental line averaged 12.2 primary and 31.5 secondary
      branches in the main panicles; two OErN lines averaged 15.0 and 15.2 primary, and
      41.5 and 44.3 secondary branches. In large-scale field trials, OErN plants
      produced at least 58.62% more total grain (by weight) compared with the parental
      line. They also had more large and small vascular bundles in the stem internodes
      and leaves. Overexpression of miR164b or down-regulation of OsNAC2 led to
      decreased panicle length and grain yield in the main panicle. The OErN plants
      showed significant up-regulation of the grain number and plant architecture
      related genes IPA1 and DEP1. A survey of >3000 rice varieties found no natural
      mutations in the miR164b-binding site of OsNAC2. OErN increased yield in
      Nipponbare and the commonly grown Yangyujing 3 cultivars. In summary, we
      identified an efficient new strategy to increase rice yield substantially and
      improve plant architecture through overexpression of OsmiR164b-resistant OsNAC2.

PMID- 29365137
TI  - Comparison of Commercial Lures and Food Baits for Early Detection of Fruit
      Infestation Risk by Drosophila suzukii (Diptera: Drosophilidae).
AB  - Drosophila suzukii (Matsumura; Diptera: Drosophilidae) is one of the most serious
      invasive pests of berries and cherries worldwide. Several adult monitoring
      systems are available to time foliar application of insecticides with the
      expectation of detecting the presence of D. suzukii before they infest
      susceptible crops. We tested this by comparing four different trapping systems
      based on two homemade baits, apple cider vinegar (ACV) or fermenting dough, and
      two fermentation volatile-based commercial lures, Scentry and Trece. Traps baited
      with dough or Scentry captured more D. suzukii than traps baited with ACV or
      Trece in blueberries and traps baited with Trece in raspberries. In blueberries,
      traps baited with Scentry, Trece and dough provided 11-21 d of warning prior to
      first detection of fruit infestation. However, these traps were not as effective
      in summer floricane raspberries. The Scentry lure baited traps detected D.
      suzukii on the same week as the first detection of fruit infestation and other
      trapping systems detected the fly 4 to 11 d after the first detection, suggesting
      the need for an improved D. suzukii detection system in raspberries. Both
      synthetic lures (Scentry and Trece) were significantly more selective for D.
      suzukii than dough bait, although the selectivity of all four tested lures/baits
      were relatively low at <20%. Our results suggest that in locations where D.
      suzukii adults are not trapped in late winter and spring, adult monitoring of D.
      suzukii using a sensitive trapping system may provide early warning of pending
      infestation risk thereby potentially reducing unnecessary insecticide
      applications.

PMID- 29365138
TI  - NADPH oxidase 4 function as a hydrogen peroxide sensor.
AB  - Nox4, a member of the NADPH- and oxygen-dependent oxidoreductases that generate
      reactive oxygen species (ROS), is widely expressed and constitutively active. To
      understand better its function and regulation, specific mutations in the Nox4
      dehydrogenase (DH) domain were examined for effects on Nox4 oxidase activity.
      Transfection of His6-tagged Nox4 increased the amount of p22phox subunit in
      HEK293 cells, and a higher level of the heterodimer was observed in the nucleus
      enriched fraction (NEF). NEF from Nox4-expressing HEK293 cells exhibited oxygen
      and H2O2 concentration-dependent NADPH oxidation rate. In Nox4-expressing cells,
      NEF and its partially purified form, the Nox4(P437H) mutant almost completely
      lost its oxidase activity, while Nox4(C546S), Nox4(C546L) or/and (C547L) had a
      significantly decreased rate of ROS production. The NADPH-dependent reduction of
      cytochrome c or cytochrome b5 by purified Nox4 DH domain was found regulated by
      the H2O2 concentration, and C546L and C547L mutants showed lower rates of the
      hemeprotein reduction. These conserved Cys residues in the DH domain respond to
      the cytosolic H2O2 concentration to regulate Nox4 activity.

PMID- 29365139
TI  - Rodents as Natural Hosts of Zoonotic Schistosoma Species and Hybrids: An
      Epidemiological and Evolutionary Perspective From West Africa.
AB  - The complex multi-host disease dynamics of schistosomiasis and Schistosoma spp.,
      including the emergence of zoonotic parasite hybrids, remain largely unexplored
      in West Africa. We elucidated the role of wild small mammals as reservoir for
      zoonotic Schistosoma species and hybrids in endemic areas of Senegal. We
      identified Schistosoma mansoni, Schistosoma bovis, and a Schistosoma
      haematobium/S. bovis hybrid, with local prevalence in wild rodents ranging from
      1.9% to 28.6%. Our findings indicate that rodents may be an important local
      reservoir for zoonotic schistosomiasis in endemic areas of West Africa,
      amplifying transmission to humans and acting as natural definitive hosts of
      schistosome hybrids.

PMID- 29365140
TI  - Development of a High-Throughput Laboratory Bioassay for Testing Potential
      Attractants for Terrestrial Snails and Slugs.
AB  - Invasive snails and slugs are among the most damaging pests of vegetables,
      fruits, ornamentals, grains, and forage throughout the world. Current control
      strategies are focused almost exclusively on molluscicides, which are ineffective
      under some conditions, and which can have serious nontarget effects. A major aim
      of this study was to develop a generic high-throughput bioassay method for use in
      identifying attractants for terrestrial gastropods, with the overall goal of
      developing attractant-based control methods for pest gastropods. Here, we
      demonstrate the use of the bioassay method in screening a wide variety of
      foodstuffs and other possible sources of attractants, using the pest snail Cornu
      aspersum Muller (Pulmonata, Helicidae) and the pest slug Deroceras reticulatum
      Muller (Pulmonata, Agriolimacidae) as test animals. Among a large number of food
      items and previously reported attractants tested, chopped fresh cucumber (Cucumis
      sativus) was the most attractive substrate for both species. Our results also
      showed that previous feeding experience influences subsequent food choice to some
      extent, but regardless of previous feeding experience, chopped cucumber was as
      attractive or more attractive than any other substrate tested.

PMID- 29365141
TI  - Attraction of Aphidius ervi (Hymenoptera: Braconidae) and Aphidoletes aphidimyza
      (Diptera: Cecidomyiidae) to Sweet Alyssum and Assessment of Plant Resources
      Effects on their Fitness.
AB  - The green peach aphid Myzus persicae (Sulzer) (Hemiptera: Aphididae) is one of
      the most economically important aphid species affecting crops worldwide. Since
      many natural enemies of this aphid have been recorded, biological control of this
      pest might be a viable alternative to manage it. Selected plant species in field
      margins might help to provide the natural enemies with food sources to enhance
      their fitness. This study aimed to investigate if sweet alyssum, Lobularia
      maritima (L.) (Brassicaceae), is a potential food source for the parasitoid
      Aphidius ervi Haliday (Hymenoptera: Braconidae) and the predator Aphidoletes
      aphidimyza (Rondani) (Diptera: Cecidomyiidae), and whether this flower could
      contribute to enhance the biological control of M. persicae. Volatiles produced
      by alyssum, with and without flowers, attracted both natural enemies. This
      attractiveness to alyssum flowers was disrupted when compared with peach shoots
      recently infested with a relatively low number of aphids. When aphids were
      absent, parasitoids exposed to alyssum survived longer than those that fed on a
      sugar solution or on water. In the case of the predator, alyssum flowers did not
      benefit longevity since the nectaries were inaccessible to females. However, our
      results provide evidence that A. aphidimyza would be able to feed on nectar if
      accessible. The floral resource did not improve the reproductive capacity of the
      two natural enemies, but the 10% sugar solution increased the egg load of the
      predator. Provision of other sugar resources, such as flowers with exposed
      nectaries and extra floral nectar may also be a viable option to improve the
      biological control of M. persicae.

PMID- 29365142
TI  - Intramuscular Adeno-Associated Virus-Mediated Expression of Monoclonal Antibodies
      Provides 100% Protection Against Ebola Virus Infection in Mice.
AB  - The 2013-2016 West Africa outbreak demonstrated the epidemic potential of Ebola
      virus and highlighted the need for counter strategies. Monoclonal antibody (mAb)
      based therapies hold promise as treatment options for Ebola virus infections.
      However, production of clinical-grade mAbs is labor intensive, and immunity is
      short lived. Conversely, adeno-associated virus (AAV)-mediated mAb gene transfer
      provides the host with a genetic blueprint to manufacture mAbs in vivo, leading
      to steady release of antibody over many months. Here we demonstrate that AAV
      mediated expression of nonneutralizing mAb 5D2 or 7C9 confers 100% protection
      against mouse-adapted Ebola virus infection, while neutralizing mAb 2G4 was 83%
      protective. A 2-component cocktail, AAV-2G4/AAV-5D2, provided complete protection
      when administered 7 days prior to challenge and was partially protective with a 3
      day lead time. Finally, AAV-mAb therapies provided sustained protection from
      challenge 5 months following AAV administration. AAV-mAb may be a viable
      alternative strategy for vaccination against emerging infectious diseases.

PMID- 29365143
TI  - Improved Sweetpotato Whitefly and Potato Psyllid Control in Tomato by Combining
      the Mirid Dicyphus hesperus (Heteroptera: Miridae) With Specialist Parasitic
      Wasps.
AB  - Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) and Bactericera cockerelli
      Sulcer (Hemiptera: Psyllidae) are important pests in tomato, and the mirid
      Dicyphus hesperus Knight (Heteroptera: Miridae) has been shown as an effective
      predator of both pests. Although the predator was able to suppress populations of
      both pests, the remaining levels could still exceed tolerable levels. Thus, we
      here hypothesized whether the combination of D. hesperus with the specialist
      parasitoids Eretmocerus eremicus Rose y Zolnerowich (Hymenoptera: Aphelinidae)
      (whitefly) and Tamarixia triozae (Burks) (Hymenoptera: Eulophidae) (psyllid)
      would result in better pest control on a greenhouse scale. For that, we conducted
      a trial in which we compared the results against B. tabaci and B. cockerelli in
      greenhouses treated with D. hesperus alone or the predator in combination with
      the specialist parasitoids. The results showed that the predator was able to
      establish and suppress B. tabaci and B. cockerelli in tomato, but the addition of
      the specialist parasitoids resulted in better and more cost-effective pest
      control. Implementation of this method would therefore increase the robustness
      and reliability of biocontrol-based integrated pest management programmes for
      tomato crops, over methods based exclusively on D. hesperus release.

PMID- 29365144
TI  - Immune-Active Microenvironment in Small Cell Carcinoma of the Ovary,
      Hypercalcemic Type: Rationale for Immune Checkpoint Blockade.
AB  - Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a highly
      aggressive monogenic cancer driven by SMARCA4 mutations. Here, we report
      responses to anti-PD1 immunotherapy in four patients and characterize the immune
      landscape of SCCOHT tumors using quantitative immunofluorescence and gene
      expression profiling. Unexpectedly for a low mutation burden cancer, the majority
      of the tumors (eight of 11 cases) demonstrated PD-L1 expression with strong
      associated T-cell infiltration (R2 = 0.60-0.95). PD-L1 expression was detected in
      both tumor and stromal cells, with macrophages being the most abundant PD-L1
      positive cells in some tumors (three of 11 cases). Transcriptional profiling
      revealed increased expression of genes related to Th1 and cytotoxic cell function
      in PD-L1-high tumors, suggesting that PD-L1 acts as a pathway of adaptive immune
      resistance in SCCOHT. These findings suggest that although SCCOHT are low
      mutational burden tumors, their immunogenic microenvironment resembles the
      landscape of tumors that respond well to treatment with PD-1/PD-L1 blockade.

PMID- 29365146
TI  - Rat Poisoning: A Challenging Diagnosis With Clinical and Psychological
      Implications.
AB  - Rat poisoning should be considered in the differential diagnosis of a patient
      presenting with signs and symptoms of vitamin K deficiency without a more likely
      explanation. However, confirming this diagnosis may be difficult due to the
      varying sensitivities of available assays. A 40-year-old Caucasian woman
      presented to our hospital with chronic abdominal pain, hematuria, and a history
      of diarrhea of unknown etiology, despite an extensive work-up. Her laboratory
      evaluation results were consistent with vitamin K deficiency. Because she
      reported that she had not ingested warfarin, rat poisoning was suspected;
      however, the results of the first assay were negative. A second specimen was sent
      to another reference laboratory with a more sensitive assay, and the diagnosis of
      brodifacoum poisoning was confirmed. The patient was treated with oral vitamin K.
      If a patient presents with unexplained signs and symptoms of vitamin K
      deficiency, toxicological evaluation should be performed and repeat testing may
      be warranted, depending on the sensitivity of the original testing method.

PMID- 29365145
TI  - PhyloChromoMap, a Tool for Mapping Phylogenomic History along Chromosomes,
      Reveals the Dynamic Nature of Karyotype Evolution in Plasmodium falciparum.
AB  - The genome of Plasmodium falciparum, the causative agent of malaria in Africa,
      has been extensively studied since it was first fully sequenced in 2002. However,
      many open questions remain, including understanding the chromosomal context of
      molecular evolutionary changes (e.g., relationship between chromosome map and
      phylogenetic conservation, patterns of gene duplication, and patterns of
      selection). Here, we present PhyloChromoMap, a method that generates a
      phylogenomic map of chromosomes from a custom-built bioinformatics pipeline.
      Using P. falciparum 3D7 as a model, we analyze 2,116 genes with homologs in up to
      941 diverse eukaryotic, bacterial and archaeal lineages. We estimate the level of
      conservation along chromosomes based on conservation across clades, and identify
      "young" regions (i.e., those with recent or fast evolving genes) that are
      enriched in subtelomeric regions as compared with internal regions. We also
      demonstrate that patterns of molecular evolution for paralogous genes differ
      significantly depending on their location as younger paralogs tend to be found in
      subtelomeric regions whereas older paralogs are enriched in internal regions.
      Combining these observations with analyses of synteny, we demonstrate that
      subtelomeric regions are actively shuffled among chromosome ends, which is
      consistent with the hypothesis that these regions are prone to ectopic
      recombination. We also assess patterns of selection by comparing dN/dS ratios of
      gene family members in subtelomeric versus internal regions, and we include the
      important antigenic gene family var. These analyses illustrate the highly dynamic
      nature of the karyotype of P. falciparum, and provide a method for exploring
      genome dynamics in other lineages.

PMID- 29365147
TI  - Prepartum fatty acid supplementation in sheep I. Eicosapentaenoic and
      docosahexaenoic acid supplementation do not modify ewe and lamb metabolic status
      and performance through weaning.
AB  - Fatty acids are involved in the regulation of many physiological pathways,
      including those involved in gene expression and energy metabolism. Through
      effects on these pathways, fatty acids may have lifelong impacts on offspring
      development and metabolism via maternal supplementation. Therefore, our objective
      was to investigate the impact of supplementing a source of omega-3 fatty acids
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) during late gestation
      on productive and metabolic responses of ewes and their offspring. Eighty-four
      gestating ewes (28 pens) were blocked and randomly assigned to a diet with 0.39%
      added fat during the last 50 d of gestation (d -0). The fat sources were Ca salts
      of a palmitic fatty acid distillate (PFAD) or EPA + DHA. After lambing (d 1), all
      ewes and lambs were placed on the same pasture. The ewes were weighed and BCS was
      measured on d -50, -20, 30, and 60 (weaning) of the experiment. Blood samples
      were taken from the ewes on d -50, -20, 1 (lambing), 30, and 60. Milk yield and
      composition were measured at 30 d postpartum. Lambs were weighed and bled at d 1,
      30, and 60, and ADG was calculated. All plasma samples were analyzed for glucose
      and NEFA. Ghrelin, prostaglandin E metabolites (PGEM), and the prostaglandin D2
      metabolite 11beta-PGF2alpha were measured in d -20 ewe samples. Insulin and
      adropin were measured in lamb samples at d 60. There was no difference on ewe BW
      (P = 0.48) or BCS (P = 0.55), or plasma concentrations of glucose (P = 0.57),
      NEFA (P = 0.44), ghrelin (P = 0.36), PGEM (P = 0.32), and 11beta-PGF2alpha (P =
      0.86) between ewes supplemented with PFAD or EPA + DHA. Neither milk yield nor
      its composition was different (P > 0.10) among treatments. Lambs born from ewes
      supplemented with PFAD or EPA + DHA did not have different BW (P = 0.22), ADG (P
      = 0.21) or plasma NEFA (P = 0.52), glucose (P = 0.50), insulin (P = 0.59), and
      adropin (P = 0.72) concentrations. These results suggest that supplementation of
      EPA and DHA during late gestation did not affect ewe metabolic profile or milk
      production. Lamb performance and metabolism through weaning were not affected by
      maternal supplementation with an enriched source of EPA and DHA.

PMID- 29365148
TI  - Spinosad- and Deltamethrin-Induced Impact on Mating and Reproductive Output of
      the Maize Weevil Sitophilus zeamais.
AB  - Assessments of acute insecticide toxicity frequently focus on the lethal effects
      on individual arthropod pest species and populations neglecting the impacts and
      consequences of sublethal exposure. However, the sublethal effects of
      insecticides may lead to harmful, neutral, or even beneficial responses that may
      affect (or not) the behavior and sexual fitness of the exposed insects.
      Intriguingly, little is known about such effects on stored product insect pests
      in general and the maize weevil in particular. Thus, we assessed the sublethal
      effects of spinosad and deltamethrin on female mate-searching, mating behavior,
      progeny emergence, and grain consumption by maize weevils. Insecticide exposure
      did not affect the resting time, number of stops, and duration of mate-searching
      by female weevils, but their walking velocity was compromised. Maize weevil
      couples sublethally exposed to deltamethrin and spinosad exhibited altered
      reproductive behavior (walking, interacting, mounting, and copulating), but
      deltamethrin caused greater impairment. Curiously, higher grain consumption and
      increased progeny emergence were observed in deltamethrin-exposed insects,
      suggesting that this pyrethroid insecticide elicits hormesis in maize weevils
      that may compromise control efficacy by this compound. Although spinosad has less
      of an impact on weevil reproductive behavior than deltamethrin, this
      bioinsecticide also benefited weevil progeny emergence, but did not affect grain
      consumption. Therefore, our findings suggest caution using either compound, and
      particularly deltamethrin, for controlling the maize weevil, as they may actually
      favor this species population growth when in sublethal exposure requiring further
      assessments. The same concern may be valid for other insecticides as well, what
      deserves future attention.

PMID- 29365149
TI  - A Proposed Concentration-Controlled New Protocol for Optimal Corneal Crosslinking
      Efficacy in the Anterior Stroma.

PMID- 29365150
TI  - Quantification of Macular Microvascular Changes in Patients With Retinitis
      Pigmentosa Using Optical Coherence Tomography Angiography.
AB  - Purpose: To evaluate the microvascular changes in eyes with RP quantitatively
      using optical coherence tomography angiography (OCTA) and to determine whether
      the correlations between these indices and the severity of RP are significant.
      Methods: This was a retrospective, observational study. The medical records of 53
      RP patients and 46 controls were reviewed. The OCTA images were obtained with the
      Cirrus 5000 with Angioplex, and an automated program was used to analyze the
      microvascular patterns. The perfusion density (PD) and vessel length density
      (VLD) were used as indices of the microvascular density, whereas the vessel
      diameter index (VDI) was used as a measure of the caliber of the vessels. The
      width of the ellipsoid zone (EZ) in the OCT images and the mean deviation (MD) of
      the Humphry Field Analyzer (HFA) were used to determine the severity of the RP.
      Student's t-tests and Spearman's correlation tests were used. Results: Both the
      PD and VLD in the superficial and deep plexuses and the whole retina were
      significantly reduced, and the VDI was significantly increased in RP patients
      compared with the corresponding values of the controls (P < 0.001). Spearman's
      rank tests indicated the RP severity was significantly correlated with the PD and
      VLD in all three layers (P < 0.001, r ranging from 0.50 to 0.87) and
      significantly correlated with VDI in the deep and the whole retina (P < 0.001,
      ranging from -0.64 to -0.73). Conclusions: Quantitative changes in the
      microvascular density might be useful for examining the pathophysiology of RP.

PMID- 29365151
TI  - Lack of Evidence for Transovarial Transmission of the Lyme Disease Spirochete
      Borrelia mayonii by Infected Female Ixodes scapularis (Acari: Ixodidae) Ticks.
AB  - The recently described Lyme disease spirochete Borrelia mayonii is associated
      with human illness in the Upper Midwest of the United States. Experimental
      laboratory studies and field observations on natural infection indicate that B.
      mayonii is maintained by horizontal transmission between tick vectors and
      vertebrate reservoirs. While maintaining a colony of Ixodes scapularis Say
      (Acari: Ixodidae) ticks infected with the B. mayonii type strain (MN14-1420), we
      had an opportunity to examine whether infected females may pass this spirochete
      transovarially to their offspring. We found no evidence of B. mayonii infection
      in subsets of larvae originating from 18 infected I. scapularis females (grand
      total of 810 larvae tested), or in mice exposed to larval feeding.

PMID- 29365152
TI  - Protein-mediated looping of DNA under tension requires supercoiling.
AB  - Protein-mediated DNA looping is ubiquitous in chromatin organization and gene
      regulation, but to what extent supercoiling or nucleoid associated proteins
      promote looping is poorly understood. Using the lac repressor (LacI), a
      paradigmatic loop-mediating protein, we measured LacI-induced looping as a
      function of either supercoiling or the concentration of the HU protein, an
      abundant nucleoid protein in Escherichia coli. Negative supercoiling to
      physiological levels with magnetic tweezers easily drove the looping probability
      from 0 to 100% in single DNA molecules under slight tension that likely exists in
      vivo. In contrast, even saturating (micromolar) concentrations of HU could not
      raise the looping probability above 30% in similarly stretched DNA or 80% in DNA
      without tension. Negative supercoiling is required to induce significant looping
      of DNA under any appreciable tension.

PMID- 29365153
TI  - Screening Arabidopsis thaliana mutants for low sensitivity to manganese
      identifies novel alleles of NRAMP1 and PGSIP6.
AB  - Manganese (Mn) is an essential micronutrient; however, few genes required for
      growth under low-Mn conditions have been identified. In this study, we isolated
      Arabidopsis thaliana mutants sensitive to low-Mn conditions from ethyl
      methanesulfonate-mutagenized seeds. Among them, we identified the causal genes of
      two mutants. One mutant (35-34) exhibited a short root phenotype and low Mn
      concentration in the shoots. The other mutant (30-11) exhibited a small shoot
      phenotype with Mn concentrations similar to the control. Genetic mapping,
      allelism tests, and gene complementation tests identified the causal genes as
      At1g80830 (NRAMP1) for 35-34 and At5g18480 (PGSIP6) for 30-11. NRAMP1 was
      previously reported to be essential for Mn uptake under low-Mn conditions, thus
      validating our screening method. PGSIP6 encodes inositol phosphorylceramide
      glucuronosyltransferase, which is involved in glycosyl inositol
      phosphorylceramide sphingolipid glycosylation. PGSIP6-green fluorescent protein
      was localized to the Golgi apparatus, which is consistent with its function in
      the glycosylation of sphingolipids. Our screening identified a novel gene
      required for low-Mn tolerance, and we also provide new insights towards
      understanding the physiological function of PGSIP6.

PMID- 29365154
TI  - Spatial Distribution and Sampling Plans With Fixed Level of Precision for Citrus
      Aphids (Hom., Aphididae) on Two Orange Species.
AB  - Aphis spiraecola Patch, Aphis gossypii Glover, and Toxoptera aurantii Boyer de
      Fonscolombe are three important aphid pests of citrus orchards. In this study,
      spatial distributions of the aphids on two orange species, Satsuma mandarin and
      Thomson navel, were evaluated using Taylor's power law and Iwao's patchiness. In
      addition, a fixed-precision sequential sampling plant was developed for each
      species on the host plant by Green's model at precision levels of 0.25 and 0.1.
      The results revealed that spatial distribution parameters and therefore the
      sampling plan were significantly different according to aphid and host plant
      species. Taylor's power law provides a better fit for the data than Iwao's
      patchiness regression. Except T. aurantii on Thomson navel orange, spatial
      distribution patterns of the aphids were aggregative on both citrus. T. aurantii
      had regular dispersion pattern on Thomson navel orange. Optimum sample size of
      the aphids varied from 30-2061 and 1-1622 shoots on Satsuma mandarin and Thomson
      navel orange based on aphid species and desired precision level. Calculated stop
      lines of the aphid species on Satsuma mandarin and Thomson navel orange ranged
      from 0.48 to 19 and 0.19 to 80.4 aphids per 24 shoots according to aphid species
      and desired precision level. The performance of the sampling plan was validated
      by resampling analysis using resampling for validation of sampling plans (RVSP)
      software. This sampling program is useful for IPM program of the aphids in citrus
      orchards.

PMID- 29365155
TI  - Comparison of Palivizumab-Like Antibody Binding to Different Conformations of the
      RSV F Protein in RSV-Infected Adult Hematopoietic Cell Transplant Recipients.
AB  - Background: Most respiratory syncytial virus (RSV) vaccine candidates include
      fusion (F) protein in different conformations. Antigenic site II found in the
      different F conformations is the target of palivizumab, the only US Food and Drug
      Administration approved monoclonal antibody (mAb). Serum palivizumab-like
      antibody (PLA) is a potential serologic correlate of immunity. Our objective was
      to determine if different conformations of F protein in a palivizumab competitive
      antibody (PCA) assay affect the PLA concentrations. Methods: Four PCA assays were
      standardized using mAbs. Each contained prefusion, postfusion, or intermediate F
      forms. PLA concentrations were measured in acute and convalescent sera from 22
      RSV/A and 18 RSV/B-infected adult hematopoietic cell transplant (HCT) recipients.
      PLA concentrations were calculated using a 4-parameter logistic regression model
      and analyzed for statistical significance. Results: PCA assays revealed
      significantly greater PLA concentrations in convalescent sera; comparable
      increases in PLA concentration in RSV/A and RSV/B-infected HCT recipients; and
      significantly reduced PLA concentrations in HCT recipients who shed RSV >=14
      days. A significant positive correlation was observed between PCA assays and RSV
      neutralizing antibody titers. Conclusions: F protein conformation does not appear
      to have a measurable impact on PCA assays for measuring PLA induced by RSV/A or
      RSV/B infection.

PMID- 29365156
TI  - Response of Pediculus humanus capitis (Phthiraptera: Pediculidae) to Volatiles of
      Whole and Individual Components of the Human Scalp.
AB  - The head louse Pediculus humanus capitis (De Geer) (Phthiraptera: Pediculidae) is
      a cosmopolitan human ectoparasite causing pediculosis, one of the most common
      arthropod parasitic conditions of humans. The mechanisms and/or chemicals
      involved in host environment recognition by head lice are still unknown. In this
      study, we evaluated the response of head lice to volatiles that emanate from the
      human scalp. In addition, we identified the volatile components of the odor and
      evaluated the attractive or repellent activity of their pure main components. The
      volatiles were collected by means of Solid Phase microextraction and the extract
      obtained was chemically analyzed by gas chromatograph-mass spectrometer. Twenty
      four volatile were identified in the human scalp odor, with the main compounds
      being the following: nonanal, sulcatone, geranylacetone, and palmitic acid. Head
      lice were highly attracted by the blend human scalp volatiles, as well as by the
      individual major components. A significant finding of our study was to
      demonstrate that nonanal activity depends on the mass of the compound as it is
      repellent at high concentrations and an attractant at low concentrations. The
      results of this study indicate that head lice may use chemical signals in
      addition to other mechanisms to remain on the host.

PMID- 29365157
TI  - Inferring Smoking Status from User Generated Content in an Online Cessation
      Community.
AB  - Introduction: User generated content (UGC) is a valuable but underutilized source
      of information about individuals who participate in online cessation
      interventions. This study represents a first effort to passively detect smoking
      status among members of an online cessation program using UGC. Methods: Secondary
      data analysis was performed on data from 826 participants in a web-based smoking
      cessation randomized trial that included an online community. Domain experts from
      the online community reviewed each post and comment written by participants and
      attempted to infer the author's smoking status at the time it was written.
      Inferences from UGC were validated by comparison with self-reported 30-day point
      prevalence abstinence (PPA). Following validation, the impact of this method was
      evaluated across all individuals and timepoints in the study period. Results: Of
      the 826 participants in the analytic sample, 719 had written at least one post
      from which content inference was possible. Among participants for whom
      unambiguous smoking status was inferred during the 30 days preceding their 3
      month follow-up survey, concordance with self-report was almost perfect (kappa =
      0.94). Posts indicating abstinence tended to be written shortly after enrollment
      (median = 14 days). Conclusions: Passive inference of smoking status from UGC in
      online cessation communities is possible and highly reliable for smokers who
      actively produce content. These results lay the groundwork for further
      development of observational research tools and intervention innovations.

PMID- 29365158
TI  - Reduced Insecticide Susceptibility in Aedes vexans (Diptera: Culicidae) Where
      Agricultural Pest Management Overlaps With Mosquito Abatement.
AB  - Mosquito abatement programs in Midwestern communities frequently exist within
      landscapes dominated by agriculture. Although separately managed, both
      agricultural pests and mosquitoes are targeted by similar classes of
      insecticides. As a result, there is the potential for unintended insecticide
      exposure to mosquito populations from agricultural pest management. To determine
      the impact that agricultural management practices have on mosquito insecticide
      susceptibility we compared the mortality of Aedes vexans (Meigen; Diptera:
      Culicidae) between populations sampled from locations with and without mosquito
      abatement in South Dakota, a region dominated by agricultural production.
      Collection locations were either within towns with mosquito abatement programs (n
      = 2; Brookings and Sioux Falls, SD) or located > 16 km from towns with mosquito
      abatement programs (n = 2; areas near Harrold and Willow Lake, SD). WHO bioassays
      were used to test susceptibly of adults to differing insecticide classes relative
      to their respective controls; 1) an organochlorine (dieldrin 4%), 2) an
      organophosphate (malathion 5%), and 3) a pyrethroid (lambda-cyhalothrin 0.05%).
      Corrected mortality did not significantly differ between locations with or
      without abatement; however, when locations were analized by proportion of
      developed land within the surrounding landscape pyrethroid mortality was
      significantly lower where crop production dominated the surrounding landscape and
      mosquito abatement was present. These data suggest that agricultural pest
      management may incidentally contribute to reduced mosquito susceptibility where
      overlap between agricultural pest management and mosquito abatement exists.
      Decoupling insecticide classes used by both agricultural and public health pest
      management programs may be necessary to ensure continued efficacy of pest
      management tools.

PMID- 29365159
TI  - Improvement of the nutritional value of high-protein sunflower meal for broiler
      chickens using multi-enzyme mixtures.
AB  - Two experiments were conducted to determine the effect of replacing soybean meal
      (SBM) with a high-protein sunflower meal (HiSFM) without or with multi-enzyme
      mixtures on growth performance, nutrient utilization, jejunal digesta viscosity,
      and excreta moisture in broiler chickens. In experiment 1, 400 chicks were
      divided into 40 replicates of 10 birds and fed for 35 d a corn-soybean meal
      (CSBM) control diet or CSBM with 25 (HiSFM25), 50 (HiSFM50), 75 (HiSFM75), or
      100% (HiSFM100) of total SBM replaced by HiSFM. During d 0 to 35, increasing
      HiSFM content in diets linearly reduced (P < 0.0001) BW, FI, and BW gain (BWG).
      Feeding HiSFM25 or HiSFM50 resulted in similar growth performance as CSBM (P >
      0.05). In experiment 2, 120 chicks were divided into 24 replicates of 5 birds and
      fed CSBM or HiSFM75 diet without or with enzyme A (supplying 4,000, 500, and
      8,000 U/kg of xylanase, alpha-amylase, and protease, respectively) or enzyme B
      (supplying 1,700, 1,100, 240, 30, 1,200, 360, 1,500, and 120 U/kg of cellulase,
      pectinase, mannanase, galactanase, xylanase, glucanase, amylase, and protease,
      respectively) for 21 days. Excreta moisture content was determined weekly, and
      birds were euthanized on d 22 to collect jejunal and ileal digesta for viscosity
      and apparent ileal digestibility (AID) measurements, respectively. Compared with
      CSBM, feeding HiSFM75 reduced (P < 0.05) BWG and G: F, enzymes A and D alleviated
      BWG and G: F reduction (P < 0.05), and enzyme A reduced (P = 0.037) the excreta
      moisture content, whereas the treatments did not influence AID or jejunal digesta
      viscosity measurements. In conclusion, experiment 1 results show that HiSFM can
      replace up to 50% of SBM without depressing growth performance in either the
      starter or finisher phase, whereas experiment 2 shows that enzymes A and B
      supplementation can alleviate the growth depression associated with feeding
      HiSFM75. These results suggest that enzyme supplementation can enhance HiSFM
      inclusion in broiler diets without affecting productivity or barn hygiene
      management.

PMID- 29365160
TI  - Scope and Nature of Pain- and Analgesia-Related Content of the United States
      Medical Licensing Examination (USMLE).
AB  - Background: "The ongoing opioid crisis lies at the intersection of two
      substantial public health challenges-reducing the burden of suffering from pain
      and containing the rising toll of the harms that can result from the use of
      opioid medications" [1]. Improved pain education for health care providers is an
      essential component of the multidimensional response to both still-unmet
      challenges [2,3]. Despite the importance of licensing examinations in assuring
      competency in health care providers, there has been no prior appraisal of pain
      and related content within the United States Medical Licensing Examination
      (USMLE). Methods: An expert panel developed a novel methodology for
      characterizing USMLE questions based on pain core competencies and topical and
      public health relevance. Results: Under secure conditions, raters used this
      methodology to score 1,506 questions, with 28.7% (432) identified as including
      the word "pain." Of these, 232 questions (15.4% of the 1,506 USMLE questions
      reviewed) were assessed as being fully or partially related to pain, rather than
      just mentioning pain but not testing knowledge of its mechanisms and their
      implications for treatment. The large majority of questions related to pain (88%)
      focused on assessment rather than safe and effective pain management, or the
      context of pain. Conclusions: This emphasis on assessment misses other important
      aspects of safe and effective pain management, including those specific to opioid
      safety. Our findings inform ways to improve the long-term education of our
      medical and other graduates, thereby improving the health care of the populations
      they serve.

PMID- 29365161
TI  - Evaluation of dietary calcium level and source and phytase on growth performance,
      serum metabolites, and ileum mineral contents in broiler chicks fed adequate
      phosphorus diets from one to 28 days of age.
AB  - A total of 936 one-day-old broiler chicks (Ross 308) was used to evaluate the
      effects of dietary calcium (Ca) source (1.0 and 0.6% from Ca carbonate [CC], or
      0.6% from Celtic sea minerals [CSM]) on broiler chick response to phytase
      supplementation (0, 500, or 2,500 FTU per kg of diet) in phosphorus (P) adequate
      diets. Birds were randomly assigned to 9 treatments, each replicated 8 times (4
      repeats of male and 4 repeats of female birds; 13 birds per replicate) in a
      completely randomized design. Results showed that birds fed low Ca CC diets had
      significantly (P <= 0.05) lower body weight at 14 and 21 d; weight gain during 1
      to 14 d; feed intake during 1 to 14 d and 1 to 28 d; and toe and tibia ash
      content, ileum ash, and Ca, and P contents at 28 days. Feed conversion ratio and
      feed intake between 21 and 28 d, and serum Ca, Fe, and alkaline phosphatase
      levels at 28 d of age were not affected by dietary Ca level. The negative
      influence of reducing the dietary Ca level on body weight and weight gain was
      less severe when CC was replaced with CSM, and birds fed the CSM diet had a
      significantly lower feed conversion ratio and higher tibia P content compared to
      CC. Phytase did not have a significant influence (P > 0.05) on most measured
      parameters, but significantly reduced ileum P and ash contents, especially at the
      higher level of 2,500 vs. 500 units of phytase per kg of diet. These results
      confirm that CSM has a valuable potential to improve feed conversion ratio, and
      that phytase was less effective in compensating for a significantly reduced
      dietary Ca level as it is for P.

PMID- 29365162
TI  - MicroRNA1917 targets CTR4 splice variants to regulate ethylene responses in
      tomato.
AB  - Ethylene perception is regulated by receptors, and the downstream protein
      CONSTITUTIVE TRIPLE RESPONSE1 is a key suppressor of ethylene signalling. The non
      conserved tomato (Solanum lycopersicum) microRNA1917 (Sly-miR1917) mediates
      degradation of SlCTR4 splice variants (SlCTR4sv) but the molecular details of
      this pathway remain unknown. Sly-miR1917 and the targeted SlCTR4sv are
      ubiquitously expressed in all tomato organs. Overexpression of Sly-miR1917
      enhances ethylene responses, including the triple response in etiolated
      seedlings, in the absence of ethylene, as well as epinastic petiole growth,
      accelerated pedicel abscission, and fruit ripening. Enhanced ethylene signalling
      in Sly-miR1917-overexpressing plants (1917-OE) is accompanied by up-regulation of
      ethylene biosynthesis and signalling genes, and increased ethylene emission.
      These phenotypes were recovered by repressing the positive ethylene regulator
      EIN2. Moreover, the Sly-miR1917-targeted SlCTR4 splice variant SlCTR4sv3,
      expressed specifically in the abscission zone, exhibited the opposite expression
      pattern to Sly-miR1917. Complementation of the Arabidopsis thaliana ctr-1 mutant
      and yeast two-hybrid and bimolecular fluorescence complementation assays
      suggested that SlCTR4sv3 functions in ethylene signalling. Co-expression of Sly
      miR1917 and SlCTR4sv3 in Nicotiana benthamiana further suggested that Sly-miR1917
      cleaves SlCTR4sv3 in vivo. Database homology searching revealed a Solanum
      tuberosum CTR-like splice variant containing a Sly-miR1917 binding sequence, and
      a homologue of mature Sly-miR1917 in potato, indicating a conserved function for
      miR1917 and the regulatory miRNA-mediated ethylene network in solanaceous
      species.

PMID- 29365163
TI  - Extra-Articular Retained Missiles; Is Surveillance of Lead Levels Needed?
AB  - Background: Although gunshot wounds are relatively common, lead toxicity
      associated with extra-articular retained missiles (EARMs) is an uncommon, yet
      potentially devastating, complication. Although the risk of lead toxicity with
      intra-articular retained missiles is well known, EARMs are routinely left in situ
      or only removed in selected circumstances secondary to the relatively rare
      occurrence of complications. Methods: We first describe a patient with systemic
      lead poisoning associated with retained lead fragments after a gunshot-induced
      left femoral shaft fracture. We then performed a systematic review of the
      literature to answer the following questions: (1) In the setting of retained
      extra-articular bullets and/or bullet fragments, is regular monitoring and/or
      surveillance of lead levels in the blood routinely indicated? and, if so, (2)
      what are the selected factors that portend an increased risk for elevations in
      blood lead levels in the setting of retained extra-articular bullets and/or
      bullet fragments? The systematic review was conducted according to the PRISMA
      (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting
      guidelines, of the English language literature utilizing Medline (PubMed),
      EMBASE, Cochrane, and CINAHL on the topic of lead poisoning, retained bullet, and
      gunshot wound, and then searched for additional references by manually searching
      of bibliographies of the included references. Studies were included if they
      provided clinical data on one or both of our study questions; included studies
      were evaluated using the accepted levels of evidence. Findings: Routine
      monitoring or surveillance of lead levels in blood is recommended in all cases of
      EARM at the time of hospital admission and again at discharge, followed by
      monthly intervals until 3 mo post-injury and then again at 1 yr post-injury. The
      studies identified demonstrated significant risk factors for elevated blood lead
      levels in the setting of EARM, which included the number of retained missiles and
      concomitant fracture. Discussion: Recommendations for routine monitoring and
      surveillance of blood lead levels in all cases of EARM are conflicting, but such
      monitoring appears to be warranted given that the potential risks and morbidity
      associated with systemic lead poisoning are outweighed by any potential harm of
      short-term, blood lead level monitoring. Outside of concomitant fracture, the
      evidence for making further clinical recommendations regarding selected risk
      factors that portend an increased risk for elevated blood lead levels after
      gunshot injury is weak. Larger level II and III studies are needed to determine
      the indications for and frequency of lead toxicity screening after retained EARM.

PMID- 29365164
TI  - Reaction norm for yearling weight in beef cattle using single-step genomic
      evaluation.
AB  - When the environment on which the animals are raised is very diverse, selecting
      the best sires for different environments may require the use of models that
      account for genotype by environment interaction (G * E). The main objective of
      this study was to evaluate the existence of G * E for yearling weight (YW) in
      Nellore cattle using reaction norm models with only pedigree and pedigree
      combined with genomic relationships. Additionally, genomic regions associated
      with each environment gradient were identified. A total of 67,996 YW records were
      used in reaction norm models to calculate EBV and genomic EBV. The method of
      choice for genomic evaluations was single-step genomic BLUP (ssGBLUP).
      Traditional and genomic models were tested on the ability to predict future
      animal performance. Genetic parameters for YW were obtained with the average
      information restricted maximum likelihood method, with and without adding genomic
      information for 5,091 animals. Additive genetic variances explained by windows of
      200 adjacent SNP were used to identify genomic regions associated with the
      environmental gradient. Estimated variance components for the intercept and the
      slope in traditional and genomic models were similar. In both models, the
      observed changes in heritabilities and genetic correlations for YW across
      environments indicate the occurrence of genotype by environment interactions.
      Both traditional and genomic models were capable of identifying the genotype by
      environment interaction; however, the inclusion of genomic information in
      reaction norm models improved the ability to predict animals' future performance
      by 7.9% on average. The proportion of genetic variance explained by the top SNP
      window was 0.77% for the regression intercept (BTA5) and 0.82% for the slope
      (BTA14). Single-step GBLUP seems to be a suitable model to predict genetic values
      for YW in different production environments.

PMID- 29365165
TI  - Microbial community and short-chain fatty acid profile in gastrointestinal tract
      of goose.
AB  - Goose is an economically important herbivore waterfowl supplying nutritious meat
      and eggs, high-quality liver fat, and feathers. However, biogeograhpy of the gut
      microbiome of goose remains limited. The aim of this study was to investigate the
      microbiota inhabiting 7 different gastrointestinal locations (proventriculus,
      gizzard, duodenum, jejunum, ileum, cecum, and rectum) of 180-day-old geese and
      the short-chain fatty acids (SCFA) of their metabolites based on 16S rRNA gene
      sequences and gas chromatography, respectively. Consequently, 3,886,340 sequences
      were identified into 29 phyla and 359 genera. Proteobacteria, Firmicutes,
      Bacteroidetes, Cyanobacteria, and Actinobacteria were the major phyla, in which
      Bacteroidetes (28%) and Fusobacteria (0.8%) in the cecum were significantly
      higher than those in other sections (~4.4 and 0.1%, respectively). In addition,
      Cyanobacteria in the gizzard (4.9%) was significantly higher than those in other
      gut sections except the proventriculus (2.4%). At the genus level, Bacteroides
      was the most dominant group in the cecum at 23.7%, which was much more than those
      in the 6 other sections (less than 4.6%). Moreover, Faecalibacterium and
      Butyricicoccus were significantly high in the cecum (P < 0.05). Results of SCFA
      showed that acetic and butyric acids in the cecum were significantly higher than
      those in the 6 other sections (P < 0.05); this result was consistent with the
      high abundance of Bacteroides, Faecalibacterium, Prevotella, and Butyricicoccus
      in the cecum. Additionally, isobutyric, isovaleric, and valeric acids were found
      only in the cecum. The different microbial compositions among the 7
      gastrointestinal locations might be a cause and consequence of gut functional
      differences. All these results could offer some information for future study of
      the relationship between gastrointestinal microbiota and the ability of fiber
      utilization and adaptability.

PMID- 29365167
TI  - Refining the Trauma and Injury Severity Score (TRISS) to Measure the Performance
      of the UK Combat Casualty Care System.
AB  - Introduction: The Trauma and Injury Severity Score (TRISS) methodology is used in
      both the UK and US Military trauma registries. The method relies on dividing
      casualties according to mechanism, penetrating or blunt, and uses different
      weighting coefficients accordingly. The UK Military Joint Theatre Trauma Registry
      uses the original coefficients devised in 1987, whereas the US military registry
      uses updated civilian coefficients, but it is not clear how either registry
      analyzes explosive casualties according to the TRISS methodology. This study aims
      to use the UK Military Joint Theatre Trauma Registry to calculate new TRISS
      coefficients for contemporary battlefield casualties injured by either gunshot or
      explosive mechanisms. The secondary aim of this study is to apply the revised
      TRISS coefficients to examine the survival trends of UK casualties from recent
      military conflicts. Materials and Methods: The Joint Theatre Trauma Registry was
      searched for all UK casualties injured or killed in Iraq and Afghanistan by
      explosive or gunshot mechanisms between January 1, 2003 and December 31, 2014.
      Details of these casualties including injuries and vital signs were reviewed.
      Logistic regression analysis was performed to devise new TRISS coefficients;
      these were then used to examine survival over the 12 yr of the study. Results:
      Comparing the predictions from the gunshot TRISS model to the observed outcomes,
      it demonstrates a sensitivity of 98.1% and a specificity of 96.8% and an overall
      accuracy of 97.8%. With respect to the explosive TRISS model, there is a
      sensitivity of 98.6%, a specificity of 97.4%, and an overall accuracy of 98.4%.
      When this updated and mechanism-specific TRISS methodology was used to measure
      changes in survival over the study period, survival following these injuries
      improved until 2012 when performance was maintained for the last 2 yr of the
      study. Conclusion: This study for the first time refines the TRISS methodology
      with coefficients appropriate for use within combat casualty care systems. This
      improved methodology reveals that UK combat casualty care performance appears to
      have improved until 2012 when this standard was maintained.

PMID- 29365166
TI  - Toward Return to Duty Decision-Making After Military Mild Traumatic Brain Injury:
      Preliminary Validation of the Charge of Quarters Duty Test.
AB  - Introduction: Determining duty-readiness after mild traumatic brain injury (mTBI)
      remains a priority of the United States Department of Defense as warfighters in
      both deployed and non-deployed settings continue to sustain these injuries in
      relatively large numbers. Warfighters with mTBI may experience unresolved
      sensorimotor, emotional, cognitive sequelae including problems with executive
      functions, a category of higher order cognitive processes that enable people to
      regulate goal-directed behavior. Persistent mTBI sequelae interfere with
      warfighters' proficiency in performing military duties and signal the need for
      graded return to activity and possibly rehabilitative services. Although
      significant strides have been carried out in recent years to enhance the
      identification and management of mTBI in garrison (EXORD 165-13) and deployed
      settings (EXORD 242-11; DoDI 6,490.11), the Department of Defense still lacks
      reliable, valid, and clinically feasible functional assessments to help inform
      duty-readiness decisions. Traditional functional assessments lack face validity
      for warfighters and may have ceiling effects, especially as related to executive
      functions. Performance-based multitasking assessments have been shown to be
      sensitive to executive dysfunction after acquired brain injury but no
      multitasking assessments have been validated in adults with mTBI. Existing
      multitasking assessments are not ecologically valid relative to military
      contexts. A multidisciplinary military-civilian team of researchers developed and
      evaluated a performance-based assessment called the Assessment of Military
      Multitasking Performance. One of the Assessment of Military Multitasking
      Performance multitasks, the Charge of Quarters Duty Test (CQDT), was designed to
      challenge the divided attention, foresight, and planning dimensions of executive
      functions. Here, we report on the preliminary validation results of the CQDT. 
      Materials and Methods: The team conducted a measurement development study at Fort
      Bragg, NC, enrolling 83 service members (33 with mTBI and 50 healthy controls).
      Discriminant validity was evaluated by comparing differences in CQDT sub-scores
      of warfighters with mTBI and healthy controls. Associations between CQDT sub
      scores and neurocognitive measures known to be sensitive to mTBI were examined to
      explore convergent validity. The study was approved by the Womack Army Medical
      Center Institutional Review Board (Fort Bragg). Results: There were significant
      between-group differences in two of the four CQDT sub-scores (number of visits, p
      = 0.012; and performance accuracy, p = 0.020). Correlations between the CQDT sub
      scores and some neurocognitive measures were statistically significant but weak,
      ranging from 0.287 (CQDT performance accuracy and NAB Numbers and Letters, Part
      D) to -0.421 (CQDT total number of visits and Automated Neuropsychological
      Assessment Metrics Tower Task). There were group differences in terms of
      participants' reading level, education, years in military, and stress symptoms;
      some of these characteristics may have influenced CQDT performance. Conclusions:
      The CQDT demonstrated initial evidence of discriminant validity. Further study is
      warranted to more formally evaluate convergent/divergent validity and ultimately
      how and whether this performance-based multitasking measure can inform readiness
      to return to duty after mTBI.

PMID- 29365168
TI  - Effects of the supplemental chromium form on performance and metabolic profile in
      laying hens exposed to heat stress.
AB  - This experiment was conducted to compare the effect of the supplemental chromium
      (Cr) form on performance, egg quality, and metabolic profile in laying hens
      exposed to heat stress (HS). Laying hens (n = 1800; 16-wk-old; Lohmann LSL-Lite)
      were kept in cages in temperature-controlled rooms at either 22 +/- 2 degrees C
      for 24 h/d (thermoneutral, TN) or 34 +/- 2 degrees C for 8 h/d, from 08:00 to
      17:00 h, followed by 22 degrees C for 16 h (HS) for 12 wks. Hens reared under
      both environmental conditions were fed 1 of 3 diets: a basal diet and the basal
      diet supplemented with either 1.600 mg of chromium-picolinate (CrPic, 12.43% Cr)
      or 0.788 mg of chromium-histidinate (CrHis, 25.22% Cr) per kg of diet, delivering
      200 MUg elemental Cr per kg diet. Data were analyzed by 2-way ANOVA. Exposure to
      HS caused decreases in feed intake (P < 0.0001), egg production (P < 0.0001), egg
      weight (P < 0.0001), eggshell weight (P < 0.0009), eggshell thickness (P <
      0.0001), eggshell strength (P < 0.0001), and Haugh unit (P < 0.0001),
      deterioration in feed conversion ratio (P < 0.0001), increases in serum glucose
      and cholesterol concentrations (P < 0.0001 for both), decreases in serum and egg
      yolk Cr concentrations (P < 0.0001 for both), and decreases in serum Na (P <
      0.002) and K (P < 0.01) concentrations. Both Cr sources were equally effective in
      alleviating performance variables under the HS condition. However, neither Cr
      sources alleviated deteriorations in egg quality parameters and serum
      electrolytes. Both Cr sources decreased serum glucose and cholesterol
      concentrations and increased serum and egg yolk Cr concentrations under the HS
      condition. In conclusion, HS adversely affected laying performance, egg quality,
      and metabolic profile. Both CrPic and CrHis partially alleviated the adverse
      effect of HS on these parameters. Inclusion of either Cr source could be a part
      of nutritional management strategies to overcome the adverse effects of HS
      performance and metabolic profile in laying hens.

PMID- 29365170
TI  - Origin of Pest Lineages of the Colorado Potato Beetle (Coleoptera:
      Chrysomelidae).
AB  - Colorado potato beetle (Leptinotarsa decemlineata Say [Coleoptera:
      Chrysomelidae]) is a pest of potato throughout the Northern Hemisphere, but
      little is known about the beetle's origins as a pest. We sampled the beetle from
      uncultivated Solanum host plants in Mexico, and from pest and non-pest
      populations in the United States and used mitochondrial DNA and nuclear loci to
      examine three hypotheses on the origin of the pest lineages: 1) the pest beetles
      originated from Mexican populations, 2) they descended from hybridization between
      previously divergent populations, or 3) they descended from populations that are
      native to the Plains states in the United States. Mitochondrial haplotypes of non
      pest populations from Mexico and Arizona differed substantially from beetles
      collected from the southern plains and potato fields in the United States,
      indicating that beetles from Mexico and Arizona did not contribute to founding
      the pest lineages. Similar results were observed for AFLP and microsatellite data
      . In contrast, non-pest populations from the states of Colorado, Kansas,
      Nebraska, New Mexico, and Texas were genetically similar to U.S. pest
      populations, indicating that they contributed to the founding of the pest
      lineages. Most of the pest populations do not show a significant reduction in
      genetic diversity compared to the plains populations in the United States. We
      conclude that genetically heterogeneous beetle populations expanded onto potato
      from native Solanum hosts. This mode of host range expansion may have contributed
      to the abundant genetic diversity of contemporary populations, perhaps
      contributing to the rapid evolution of climate tolerance, host range, and
      insecticide resistance.

PMID- 29365169
TI  - Non-B-Form DNA Is Enriched at Centromeres.
AB  - Animal and plant centromeres are embedded in repetitive "satellite" DNA, but are
      thought to be epigenetically specified. To define genetic characteristics of
      centromeres, we surveyed satellite DNA from diverse eukaryotes and identified
      variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations.
      Organisms lacking centromeric dyad symmetries had binding sites for sequence
      specific DNA-binding proteins with DNA-bending activity. For example, human and
      mouse centromeres are depleted for dyad symmetries, but are enriched for non-B
      form DNA and are associated with binding sites for the conserved DNA-binding
      protein CENP-B, which is required for artificial centromere function but is
      paradoxically nonessential. We also detected dyad symmetries and predicted non-B
      form DNA structures at neocentromeres, which form at ectopic loci. We propose
      that centromeres form at non-B-form DNA because of dyad symmetries or are
      strengthened by sequence-specific DNA binding proteins. This may resolve the CENP
      B paradox and provide a general basis for centromere specification.

PMID- 29365171
TI  - Epigenomics in 3D: importance of long-range spreading and specific interactions
      in epigenomic maintenance.
AB  - Recent progresses of genome-wide chromatin conformation capture techniques have
      shown that the genome is segmented into hierarchically organized spatial
      compartments. However, whether this non-random 3D organization only reflects or
      indeed contributes-and how-to the regulation of genome function remain to be
      elucidated. The observation in many species that 3D domains correlate strongly
      with the 1D epigenomic information along the genome suggests a dynamic coupling
      between chromatin organization and epigenetic regulation. Here, we posit that
      chromosome folding may contribute to the maintenance of a robust epigenomic
      identity via the formation of spatial compartments like topologically-associating
      domains. Using a novel theoretical framework, the living chromatin model, we show
      that 3D compartmentalization leads to the spatial colocalization of epigenome
      regulators, thus increasing their local concentration and enhancing their ability
      to spread an epigenomic signal at long-range. Interestingly, we find that the
      presence of 1D insulator elements, like CTCF, may contribute greatly to the
      stable maintenance of adjacent antagonistic epigenomic domains. We discuss the
      generic implications of our findings in the light of various biological contexts
      from yeast to human. Our approach provides a modular framework to improve our
      understanding and to investigate in details the coupling between the structure
      and function of chromatin.

PMID- 29365173
TI  - Transgenerationally Precipitated Meiotic Chromosome Instability Fuels Rapid
      Karyotypic Evolution and Phenotypic Diversity in an Artificially Constructed
      Allotetraploid Wheat (AADD).
AB  - Although a distinct karyotype with defined chromosome number and structure
      characterizes each biological species, it is intrinsically labile. Polyploidy or
      whole-genome duplication has played a pervasive and ongoing role in the evolution
      of all eukaryotes, and is the most dramatic force known to cause rapid karyotypic
      reconfiguration, especially at the initial stage. However, issues concerning
      transgenerational propagation of karyotypic heterogeneity and its translation to
      phenotypic diversity in nascent allopolyploidy, at the population level, have yet
      to be studied in detail. Here, we report a large-scale examination of
      transgenerationally propagated karyotypic heterogeneity and its phenotypic
      manifestation in an artificially constructed allotetraploid with a genome
      composition of AADD, that is, involving two of the three progenitor genomes of
      polyploid wheat. Specifically, we show that 1) massive organismal karyotypic
      heterogeneity is precipitated after 12 consecutive generations of selfing from a
      single euploid founder individual, 2) there exist dramatic differences in
      aptitudes between subgenomes and among chromosomes for whole-chromosome gain
      and/or loss and structural variations, 3) majority of the numerical and
      structural chromosomal variations are concurrent due to mutual contingency and
      possible functional constraint, 4) purposed and continuous selection and
      propagation for euploidy over generations did not result in enhanced karyotype
      stabilization, and 5) extent of karyotypic variation correlates with variability
      of phenotypic manifestation. Together, our results document that
      allopolyploidization catalyzes rampant and transgenerationally heritable
      organismal karyotypic heterogeneity that drives population-level phenotypic
      diversification, which lends fresh empirical support to the still contentious
      notion that whole-genome duplication enhances organismal evolvability.

PMID- 29365172
TI  - Rice DWARF14 acts as an unconventional hormone receptor for strigolactone.
AB  - Strigolactones (SLs) act as an important class of phytohormones to regulate plant
      shoot branching, and also serve as rhizosphere signals to mediate interactions of
      host plants with soil microbes and parasitic weeds. SL receptors in dicots, such
      as DWARF14 in Arabidopsis (AtD14), RMS3 in pea, and ShHTL7 in Striga, serve as
      unconventional receptors that hydrolyze SLs into a D-ring-derived intermediate
      CLIM and irreversibly bind CLIM to trigger SL signal transduction. Here, we show
      that D14 from the monocot rice can complement Arabidopsis d14 mutant and interact
      with the SL signaling components in Arabidopsis. Our results further reveal that
      rice D14, similar to SL receptors in dicots, also serves as an unconventional
      hormone receptor that generates and irreversibly binds the active form of SLs.
      These findings uncover the conserved functions of D14 proteins in monocots and
      dicots.

PMID- 29365174
TI  - Breast Cancer Treatment and Survival Among Department of Defense Beneficiaries:
      An Analysis by Benefit Type and Care Source.
AB  - Background: Use of treatment for breast cancer is dependent on the patient's
      cancer characteristics and willingness to undergo treatment and provider
      treatment recommendations. Receipt of breast cancer treatment varies by insurance
      status and type. It is not clear whether different benefit types and care sources
      differ in breast cancer treatment and outcomes among Department of Defense
      beneficiaries. Methods: The objectives of this study are to assess whether
      receipt of breast cancer treatment varied by benefit type (TRICARE Prime vs non
      Prime) or care source (direct care, purchased care, and both) and to examine
      whether survival and recurrence differed by benefit type and/or care source among
      female Department of Defense beneficiaries with the disease. Study subjects were
      women aged 40-64 yr, diagnosed with malignant breast cancer between 2003 and
      2007. Multivariable logistic regression analyses were conducted to assess the
      likelihood of receiving treatment by benefit type or care source. Multivariable
      Cox proportional hazard models were used to investigate differences in survival
      and recurrence by benefit type or care source. Findings: A total of 2,668 women
      were included in this study. Those with Prime were more likely to have
      chemotherapy, radiation, hormone therapy, breast-conserving surgery, surveillance
      mammography, and recurrence than women with non-Prime. Survival was high, with
      94.86% of those with Prime and 92.58% with non-Prime alive at the end of the
      study period. Women aged 50-59 yr with non-Prime benefit type had better survival
      than women with Prime of the same age. No survival differences were seen by care
      source. In regard to recurrence, women aged 60-64 yr with TRICARE Prime were more
      likely to have recurrent breast cancer than women with non-Prime. Additionally,
      women aged 50-59 yr who used purchased care were less likely to have a recurrence
      than women who used direct care only. Discussion/Impact/Recommendations: To our
      knowledge, this is the first study to examine breast cancer treatment and
      survival by care source and benefit type in the Military Health System. In this
      equal access health care system, no differences in treatment, except mastectomy,
      by benefit type, were observed. There were no overall differences in survival,
      although patients with non-Prime tended to have better survival in the age group
      of 50-59 yr. In regard to care source, women who utilized mostly purchased care
      or utilized both direct and purchased care were more likely to receive certain
      types of treatment, such as chemotherapy and radiation, as compared with women
      who used direct care only. However, survival did not differ between different
      care sources. Future research is warranted to further investigate variations in
      breast cancer treatment and its survival gains by benefit type and care source
      among Department of Defense beneficiaries.

PMID- 29365175
TI  - Variation in Inspection Efficacy by Member States of Wood Packaging Material
      Entering the European Union.
AB  - The use of wood packaging materials (WPMs) in international trade is recognized
      as a pathway for the movement of invasive pests and as the origin of most
      introductions of Asian longhorned beetle, Anoplophora glabripennis (Motschulsky)
      (Coleoptera: Cerambycidae) in Europe and North America. Following several pest
      interceptions on WPM associated with stone imports from China, the European Union
      (EU) agreed to survey certain categories of imports based on the EU Combined
      Nomenclature Codes for imports, which are based on the international Harmonized
      System. Between April 2013 and March 2015, 72,263 relevant consignments were
      received from China in the EU and 26,008 were inspected. Harmful organisms were
      detected in 0.9% of the consignments, and 1.1% of the imports did not have
      markings compliant with the international standard for treating WPM, ISPM 15.
      There were significant differences between the detection rates of harmful
      organisms among EU member states. In member states that inspected at least 500
      consignments, the rate of detection ranged from 6.9% in Austria and France to
      0.0% in Spain and Poland. If this difference in detection rate is the result of
      differences in the methods and intensity of inspection in different member states
      then an approximate sevenfold increase in the interception of harmful organisms
      may be achieved if all states were to achieve detection rates achieved by Austria
      and France. The EU data from 1999 to 2014 indicated an increasing number of
      interceptions of Bostrichidae and Cerambycidae since 2010. This study
      demonstrates that there is an ongoing threat of non-native forest pests being
      imported on WPM.

PMID- 29365176
TI  - An Algal Diet Accelerates Larval Growth of Anopheles gambiae (Diptera: Culicidae)
      and Anopheles arabiensis (Diptera: Culicidae).
AB  - The population sizes of Anopheles gambiae Giles (Diptera: Culicidae) and
      Anopheles arabiensis Patton (Diptera: Culicidae) increase dramatically with the
      onset of the rainy season in sub-Saharan Africa, but the ecological mechanisms
      underlying the increases are not well understood. As a first step toward to
      understand, we investigated the proliferation of algae, the major food of
      mosquito larvae, in artificial fresh water bodies exposed to sunlight for a short
      period, and old water bodies exposed to sunlight for a long period, and the
      effects thereof on the development of these anopheline larvae. We found that an
      epizoic green algal species of the genus Rhopalosolen (Chlorophyta:
      Chlorophyceae) proliferated immediately after water freshly taken from a spring
      was placed in sunlight. This alga proliferated only briefly (for ~10 d) even if
      the water was repeatedly exposed to sunlight. However, various algal species were
      observed in water that remained under sunlight for 40 d or longer (i.e., in old
      water bodies). The growth performance of larvae was higher in sunlight-exposed
      (alga-rich) water than in shade-stored (alga-poor) water. Stable isotope analysis
      suggested that these two anopheline species fed on Rhopalosolen algae in fresh
      water bodies but hardly at all on other algae occurring in the old water bodies.
      We concluded that freshly formed ground water pools facilitate high production of
      anopheline species because of the proliferation of Rhopalosolen algae therein,
      and the increase in the number of such pools in the rainy season, followed by
      rapid increases in A. gambiae and A. arabiensis numbers.

PMID- 29365177
TI  - Corrigendum to: Sleep deprivation affects fear memory consolidation: bi-stable
      amygdala connectivity with insula and ventromedial prefrontal cortex.

PMID- 29365178
TI  - Dietary Supplements: Regulatory Challenges and Issues in the Department of
      Defense.

PMID- 29365179
TI  - Collapse in the Heat - From Overhydration to the Emergency Room - Three Cases of
      Exercise-Associated Hyponatremia Associated with Exertional Heat Illness.
AB  - Exertional heat illness and exercise-associated hyponatremia continue to be a
      problem in military and recreational events. Symptoms of hyponatremia can be
      mistaken for heat exhaustion or heat stroke. We describe three cases of
      symptomatic hyponatremia initially contributed to heat illnesses. The first
      soldier was a 31-yr-old female who "took a knee" at mile 6 of a 12-mile foot
      march. She had a core temperature of 100.9 degrees F, a serum sodium level of 129
      mmol/L, and drank approximately 4.5 quarts of water in 2 h. The second case was a
      27-yr-old female soldier who collapsed at mile 11 of a 12-mile march. Her core
      temperature was 102.9 degrees F and sodium level was 131 mmol/L. She drank 5
      quarts in 2.5 h. The third soldier was a 27-yr-old male who developed nausea and
      vomiting while conducting an outdoor training event. His core temperature was
      98.7 degrees F and sodium level was 125 mmol/L. He drank 6 quarts in 2 h to
      combat symptoms of heat. All the three cases developed symptomatic hyponatremia
      by overconsumption of fluids during events lasting less than 3 h. Obtaining point
      of-care serum sodium may improve recognition of hyponatremia and guide management
      for the patient with suspected heat illness and hyponatremia. Depending on
      severity of symptoms, exercise-associated hyponatremia can be managed by fluid
      restriction, oral hypertonic broth, or with intravenous 3% saline. Utilizing an
      ad libitum approach or limiting fluid availability during field or recreational
      events of up to 3 h may prevent symptomatic hyponatremia while limiting
      significant dehydration.

PMID- 29365180
TI  - Characteristics of the antimicrobial resistance of Staphylococcus aureus isolated
      from chicken meat produced by different integrated broiler operations in Korea.
AB  - Vertical integration of the broiler industry allows producers to combine
      different biosecurity and sanitation practices, housing technologies, and feeding
      regimens to improve food safety. The purpose of this study was to investigate the
      prevalence of Staphylococcus aureus (S. aureus) and to characterize the
      antimicrobial-resistant isolates recovered from 7 different integrated broiler
      operation systems in Korea. Among 200 chicken meat samples, 94 were observed to
      be positive for S. aureus. However, the prevalence varied from 25.0 to 58.3% in
      chicken meats, indicating variation in S. aureus occurrence among the operations.
      Four methicillin-resistant S. aureus isolates (MRSA) were recovered from 3
      different operations. A high proportion of the S. aureus isolates were resistant
      to penicillins (51.2%), tetracycline (38.8%), and ciprofloxacin (CIP; 33.9%).
      Especially, 3 different operations showed a high number of CIP resistance
      (45.5~100%) and multidrug resistance (50.0~100%). Among 41 CIP-resistant S.
      aureus isolates, 75.6% showed a double amino-acid exchange of both gyrA and parC,
      with CIP minimum inhibitory concentrations (MIC) of >=32 MUg/mL. Four MRSA
      isolates showed resistance to 5 or 7 classes of antimicrobial agents, exhibiting
      oxacillin, CIP, and enrofloxacin MIC ranges of 16 to 128, 32 to 64, and 8 to 128
      MUg/mL, respectively, and had double mutations of S84L/S80F in gyrA/parC. Our
      findings suggest that S. aureus with resistance to important antimicrobial
      compounds can now be found in association with integrated broiler operations,
      providing the data to support the development of a monitoring and prevention
      program in integrated operations.

PMID- 29365181
TI  - Comparison of Body Composition Metrics for United States Air Force Airmen.
AB  - Background: The United States Air Force currently uses AFI 36-2905 for
      cardiovascular fitness standards and evaluation. Regarding its fitness test, the
      Air Force considers waist circumference (WC) twice as important as push-ups or
      sit-ups. Because of this weighting, one assumes that the Air Force considers WC
      relatively correlated with overall fitness or at least cardiovascular fitness. To
      our knowledge, the Air Force has not considered on a large scale how body mass
      index (BMI), height-to-weight ratio (H-W), or waist-to-height ratio (WHtR)
      compares with WC with respect to its fitness test. Methods: Using a 5.38 million
      record database from the Air Force Fitness Management System, we evaluated how
      WC, BMI, WHtR, and H-W correlate with fitness as assessed by the 1.5-mile run in
      addition to total fitness, which incorporates the 1.5-mile run time, number of
      push-ups and sit-ups. As this previously collected data were anonymous to us,
      this study fell under the definition of exempt status and approved by the
      institutional review board overseeing Joint Base San Antonio. For each waist
      metric, we performed a simple ordinary least squares regression to ascertain the
      correlation between that particular metric and either run time or total fitness;
      when incorporating more than one explanatory variable or covariate (to control
      for age and/or sex), we performed multiple ordinary least squares regressions.
      Due to the large database size and to mitigate against a type I error, we used an
      alpha of 0.001 for all statistical hypothesis tests. Findings: Approximately 18%
      of the 5.38 million records belonged to women. With respect to sex differences,
      males appeared noticeably faster and performed more push-ups on average than
      females. The number of sit-ups completed was more comparable, with males having a
      slight advantage. Males also appeared to have larger WC, BMI, H-W, and WHtR
      measurements. We compared the ordinary least squares results between WC, H-W,
      WHtR, and BMI and ranked them by R2. Models varied in R2 from 1% to 46% depending
      on the covariates in the model, with sex having a greater effect than age.
      Whether individually or adjusting for age and sex, WHtR performed better than the
      other body composition variables with an average rank score of 1.1 and a median
      improvement of approximately 4% to the current Air Force metric of WC.
      Discussion: From our findings, we present a 20-point WHtR scoring system for the
      Air Force to use in lieu of its traditional usage of WC. We used this assessment
      chart to score all Airmen in our database and compared the results to their
      current scores on the abdominal circumference portion of the test with respect to
      predicting run time, after accounting for sex, age, and number of push-ups and
      sit-ups. The R2 value improved from 40.3 to 43.6, a relative improvement of
      approximately 8%, a fairly significant effect given the database consisted of
      over 5 million records. Future studies should investigate the longitudinal effect
      of varying waist metrics over time on run time or total fitness performance.

PMID- 29365182
TI  - pepKalc: scalable and comprehensive calculation of electrostatic interactions in
      random coil polypeptides.
AB  - Motivation: Polypeptide sequence length is the single dominant factor hampering
      the effectiveness of currently available software tools for de novo calculation
      of amino acid-specific protonation constants in disordered polypeptides. Results:
      We have developed pepKalc, a robust simulation software for the comprehensive
      evaluation of protein electrostatics in unfolded states. Our software completely
      removes the limitations of the previously reported Monte-Carlo approaches in the
      computation of protein electrostatics by using a hybrid approach that effectively
      combines exact and mean-field calculations to rapidly obtain accurate results.
      Paired with a modern architecture GPU, pepKalc is capable of evaluating
      protonation behavior for an arbitrary-size polypeptide in a sub-second time
      regime. Availability and implementation: http://protein-nmr.org and
      https://github.com/PeptoneInc/pepkalc.

PMID- 29365183
TI  - Drug immunogenicity in patients with inflammatory arthritis and secondary failure
      to tumour necrosis factor inhibitor therapies: the REASON study.
AB  - Objectives: The aims were to evaluate the prevalence of anti-drug antibodies
      (ADA) in patients with RA or SpA experiencing secondary failure to anti-TNF
      therapy and to correlate ADA presence with anti-TNF concentration and clinical
      response. Methods: This was a cross-sectional, observational study of patients
      with active RA or SpA experiencing secondary failure to etanercept (ETN),
      infliximab (INF) or adalimumab (ADL). Concomitant non-biologic DMARDs were
      permitted. Serum anti-TNF and ADA levels were measured with two-site ELISA.
      Results: Among 570 evaluable patients, those with RA (n = 276) were mostly female
      (80 vs 39%), older (56 vs 48 years), received concomitant DMARDs (83 vs 47%) and
      had maintained good clinical disease control for longer (202 vs 170 weeks)
      compared with patients with SpA (n = 294). ADA were found in 114/570 (20.0%)
      patients; 51/188 (27.1%) against INF and 63/217 (29.0%) against ADL; none against
      ETN. Of these 114 patients, 92 (81%) had no detectable serum drug concentrations.
      Proportionately more patients with SpA (31.3%) had anti-INF antibodies than those
      with RA (21.1%; P = 0.014). A significantly lower proportion of patients
      receiving concomitant DMARDs (16.5%) developed ADA than those on monotherapy
      (26.4%; P < 0.05). Conclusion: In patients with RA or SpA and secondary failure,
      the development of ADA against ADL or INF, but not ETN, appears to be one of the
      main reasons for secondary treatment failure, but not the only one. Further
      investigations are needed to determine other causes of anti-TNF failure.

PMID- 29365184
TI  - The unique epigenetic features of Pack-MULEs and their impact on chromosomal base
      composition and expression spectrum.
AB  - Acquisition and rearrangement of host genes by transposable elements (TEs) is an
      important mechanism to increase gene diversity as exemplified by the ~3000 Pack
      Mutator-like TEs in the rice genome which have acquired gene sequences (Pack
      MULEs), yet remain enigmatic. To identify signatures of functioning Pack-MULEs
      and Pack-MULE evolution, we generated transcriptome, translatome, and epigenome
      datasets and compared Pack-MULEs to genes and other TE families. Approximately
      40% of Pack-MULEs were transcribed with 9% having translation evidence, clearly
      distinguishing them from other TEs. Pack-MULEs exhibited a unique expression
      profile associated with specificity in reproductive tissues that may be
      associated with seed traits. Expressed Pack-MULEs resemble regular protein-coding
      genes as exhibited by a low level of DNA methylation, association with active
      histone marks and DNase I hypersensitive sites, and an absence of repressive
      histone marks, suggesting that a substantial fraction of Pack-MULEs are
      potentially functional in vivo. Interestingly, the expression capacity of Pack
      MULEs is independent of the local genomic environment, and the insertion and
      expression of Pack-MULEs may have altered the local chromosomal expression
      pattern as well as counteracted the impact of recombination on chromosomal base
      composition, which has profound consequences on the evolution of chromosome
      structure.

PMID- 29365185
TI  - Antibody-based targeted delivery of interleukin-4 synergizes with dexamethasone
      for the reduction of inflammation in arthritis.
AB  - Objectives: We have previously reported that F8-IL4, a fusion protein consisting
      of the F8 antibody specific to the alternatively-spliced extra domain A of
      fibronectin and of murine IL-4, cures mice with established arthritis, when used
      in combination with dexamethasone (DXM). The goal of this study was to assess
      whether other therapeutic agents, besides DXM, could induce cures in combination
      with F8-IL4 and to elucidate which leucocytes are most affected by the
      pharmacological treatment. Methods: We performed therapy experiments in mice with
      CIA, using intravenous administrations of F8-IL4 in combination with DXM, MTX,
      murine cytotoxic T-lymphocyte-associated protein 4 fused to the fragment
      crystallizable portion of murine IgG2a, as well as mAbs to murine IL17A or the
      p40 subunit of murine IL12/IL23. Histology and immunohistochemistry for the
      identification of the various leucocytes were performed on the paws of mice
      euthanized at different therapy time points. Results: Only the use of F8-IL4 in
      combination with DXM induced complete remissions, while all other combinations
      did not lead to cures. The light microscopical evaluation of paws with arthritis
      revealed a predominant infiltration of neutrophils, which substantially decreased
      24 h after treatment with F8-IL4 and DXM. Conclusion: The combination of F8-IL4
      with DXM promotes a rapid anti-arthritic action by potently inhibiting neutrophil
      activity. A fully human analogue of F8-IL4 may find clinical utility for the
      treatment of neutrophil-driven chronic inflammatory conditions.

PMID- 29365186
TI  - Dietary manganese supplementation affects mammillary knobs of eggshell
      ultrastructure in laying hens.
AB  - This study evaluated the mechanism by which dietary manganese (Mn)
      supplementation-in either an organic or inorganic form-affects mammillary knobs
      of the eggshell ultrastructure in laying hens. A total of 225 54-week-old Hy-Line
      Brown laying hens were fed a basal diet containing 27.5 mg Mn/kg feed for 2 wk,
      after which they were randomly allocated into 3 groups and fed a basal diet
      (control) or a basal diet supplemented with 120 mg Mn/kg feed from monohydrate Mn
      sulfate (an inorganic source of Mn) or with 80 mg Mn/kg feed from an amino acid
      Mn complex (an organic source of Mn) for 10 wk. For each group, 5 replicates of
      15 hens each were used with 1 hen per cage. Compared with the control, dietary Mn
      supplementation increased the mammillary-knob density of eggs at 9.5 h post
      oviposition (P < 0.05). The Mn content in both blood and eggshell gland was
      increased with the supplementation of Mn in inorganic and organic forms (P <
      0.05), but the blood Mn content was higher after inorganic-Mn supplementation as
      compared with organic-Mn supplementation (P < 0.05). RNA sequencing and
      quantitative real-time PCR analysis of the eggshell gland showed that dietary Mn
      supplementation increased the expression of genes encoding some proteoglycans,
      glycoproteins, and calcium-binding proteins in the eggshell gland (P < 0.05), and
      involved in the process of the protein glycosylation and glycan metabolism in the
      eggshell gland (P < 0.05). Overall, dietary Mn supplementation can involve in the
      process of protein glycosylation and glycan metabolism and improve the expression
      of genes encoding proteoglycans and glycoproteins in the eggshell gland, thus
      increasing the mammillary-knob density during the initial deposition stage of
      shell formation.

PMID- 29365187
TI  - Effectiveness of clinical practice change strategies in improving dietitian care
      for head and neck cancer patients according to evidence-based clinical
      guidelines: a stepped-wedge, randomized controlled trial.
AB  - Best practice guidelines make a number of recommendations regarding dietitian
      management of head and neck cancer (HNC) patients. Randomized trials assessing
      the effectiveness of clinical practice change strategies for improving the
      nutritional management of HNC patients have not previously been conducted. The
      purpose of this study was to evaluate the effect of practice change strategies on
      improving the implementation of best practice guideline recommendations for the
      nutritional management of HNC patients. Four Australian radiotherapy departments
      participated in a stepped-wedge, randomized controlled trial. Baseline data were
      collected across all sites simultaneously, and the intervention was then
      introduced to each site sequentially, in a randomly determined order. During the
      intervention phase, sites received a range of supportive clinical practice change
      strategies to facilitate dietitian adherence to clinical practice guidelines. To
      assess the associated practice change by dietetic staff, we evaluated the change
      in implementation of six guideline recommendations for dietitians from
      preintervention to postintervention periods. Adherence to the clinical practice
      guidelines during the preintervention period was generally very low. The clinical
      practice change strategies significantly improved the odds of provision of four
      of the six guideline recommendations. The study found the intervention
      significantly enhanced dietitian provision of recommended care for HNC patients
      during the postintervention period. This finding holds clinical importance for
      clinician and health service effective implementation of guideline
      recommendations as well as HNC patient treatment outcomes. Trial registration
      number ACTRN12613000320752, https://www.anzctr.org.au.

PMID- 29365188
TI  - Overuse Injuries in the IDF's Combat Training Units: Rates, Types, and Mechanisms
      of Injury.
AB  - Introduction: Overuse injuries are responsible for most lost training days and
      attrition from combat training in the Israeli Defense Forces (IDF) as in armies
      around the world. The purpose of this study is to understand the rates, types,
      and mechanism of occurrence of overuse injuries in the IDF in order to provide
      the IDF's commanders a detailed updated situation report in order to enable
      commanders decision-making, prevention policy, and further research of this
      highly significant military public health issue. Methods: A cross-sectional study
      including 20,000 soldiers recruited to combat units during the year of 2013 was
      performed. Most of the data were collected from the IDF's computerized medical
      consultation records package. Descriptive statistics (percent, mean, standard
      deviation, and median) were used in order to express results. The study was
      approved by the IDF's institutional review board. Results: The overall injury
      rate was 24.5%. The total number of injuries was 6,393 with an average of 1.32 +/
      0.22 injuries per injured soldier. The injury rate was 18.4% in the infantry
      units and 36.1% in non-infantry units. Of all injuries, 87% occurred in the lower
      back and lower limb regions. The most frequent injury sites were the calf and
      ankle (34%), the knee region (22%), and the lower back (19%). Of all injuries,
      74% occurred during running (45%) or long-distance walking (29%). The average
      lost training days due to injuries was 9 d per soldier and 6.5 d per injury. The
      total number of stress fractures was 494-2.5% of all soldiers (four fractures per
      100 person years). The calf and ankle region was the most frequent site of stress
      fractures and accounted for 84% of all stress fractures, the vast majority of
      them (95%) were fractures of the distal tibia. The average number of lost
      training days due to stress fractures was 16 +/- 6.1 per fracture. Conclusions:
      As in other armies around the world, overuse injuries in the IDF are a major
      public health problem and poses a significant challenge to the IDF's commanders
      and the medical corps policy leaders. Further studies should be performed in
      order to identify the risk factors for these injuries especially in the lower
      back and the lower limb regions as part of the effort to try and reduce the rates
      of these injuries as much as possible. This study emphasizes the need for a
      continuous surveillance and monitoring system for overuse injuries as a
      significant and integral component of any intervention plan in the domain of
      overuse injuries.

PMID- 29365189
TI  - Picking up the Pieces.

PMID- 29365190
TI  - Bone disease in nephropathic cystinosis is related to cystinosin-induced
      osteoclastic dysfunction.
AB  - Background: Bone impairment is a poorly described complication of nephropathic
      cystinosis (NC). The objectives of this study were to evaluate in vitro effects
      of cystinosin (CTNS) mutations on bone resorption and of cysteamine treatment on
      bone cells [namely human osteoclasts (OCs) and murine osteoblasts]. Methods:
      Human OCs were differentiated from peripheral blood mononuclear cells (PBMCs) of
      patients and healthy donors (HDs). Cells were treated with increasing doses of
      cysteamine in PBMCs or on mature OCs to evaluate its impact on differentiation
      and resorption, respectively. Similarly, cysteamine-treated osteoblasts derived
      from murine mesenchymal stem cells were assessed for differentiation and activity
      with toxicity and proliferation assays. Results: CTNS was expressed in human OCs
      derived from HDs; its expression was regulated during monocyte colony-stimulating
      factor- and receptor activator of nuclear factor-kappaB-dependent
      osteoclastogenesis and required for efficient bone resorption. Cysteamine had no
      impact on osteoclastogenesis but inhibited in vitro HD osteoclastic resorption;
      however, NC OC-mediated bone resorption was impaired only at high doses. Only low
      concentrations of cysteamine (50 MUM) stimulated osteoblastic differentiation and
      maturation, while this effect was no longer observed at higher concentrations
      (200 uM). Conclusion: CTNS is required for proper osteoclastic activity. In vitro
      low doses of cysteamine have beneficial antiresorptive effects on healthy human
      derived OCs and may partly correct the CTNS-induced osteoclastic dysfunction in
      patients with NC. Moreover, in vitro low doses of cysteamine also stimulate
      osteoblastic differentiation and mineralization, with an inhibitory effect at
      higher doses, likely explaining, at least partly, the bone toxicity observed in
      patients receiving high doses of cysteamine.

PMID- 29365191
TI  - Vape and Aviate: Electronic-Cigarette Use and Misuse in Naval Aviation.
AB  - Introduction: Electronic cigarettes (EC) are an emerging form of nicotine
      replacement that has had a discernible increase in prevalence in the general
      population. Little is known regarding EC use among different military demographic
      groups or the extent of influence that social determinants of health may have on
      the behavior. The purpose of this study was to assess the prevalence and
      correlates of EC use in a select population of active duty U.S. Naval personnel.
      This study is unique in that it allows for EC behavior comparison between a
      traditionally healthy demographic (aviators, a subset of aircrew) and a
      representative general military population sample. Materials and methods: Cross
      sectional survey data were collected anonymously and analyzed in 2015-2016.
      Active duty Naval personnel (n = 977) were asked about ever trying ECs, frequency
      of use, and when was the last time an EC was used. Participants were assessed
      similarly regarding cigarette use. Descriptive and inferential statistics as well
      as multinomial logistic regression analyses were conducted using categorical and
      ordinal variables assigned to usage and demographic factors. This protocol was
      approved by the Institutional Review Board at Naval Hospital Portsmouth located
      in Portsmouth, Virginia. Results: Within the study population, 31.4% have tried
      ECs, 9.3% were current users, and only 3.8% were dual (EC and cigarettes) users.
      EC use was significantly associated with paygrade (enlisted), primary job duty
      (non-aircrew), and education (less than a bachelor degree, p < 0.001, p < 0.01,
      and p < 0.001, respectively). ECs were used at some point as a smoking cessation
      tool for 43.6% of current EC users (p < 0.001), 21.6% of current smokers, and
      only 5.6% of former smokers. Continued EC use after ever trying ECs (30.0%) was
      only slightly more prevalent as continued cigarette use after ever trying
      cigarettes (27.3%). Smokers were nearly five times more likely to currently use
      ECs compared with non-smokers. Trying cigarettes was associated with nearly 12
      times the risk for trying ECs compared with those who never tried cigarettes. No
      significant misuse of ECs was noted; however, several cases of drinking, tasting,
      and touching EC fluid were reported. Conclusion: This study is unique in that it
      examines the use of electronic cigarettes among selected healthy and baseline
      groups within the active duty U.S. Navy population. The current prevalence of EC
      use among active duty personnel is much higher than previously thought. Continued
      use of ECs after ever trying them appears to exceed that of cigarettes even among
      healthy populations such as aircrew. The findings of increased risk of EC use
      among those with lower income and less than a bachelor's degree suggest social
      determinants of health implications. This study sheds new light on EC use,
      characteristics of use, addiction implications, and highlights concerns for a
      growing health risk behavior.

PMID- 29365192
TI  - Stability of New Erythrocyte and Reticulocyte Parameters in Testing for Anemia on
      the Sysmex XN 9000.
AB  - Background: New erythrocyte and reticulocyte parameters provide improved
      classification of anemia and monitoring of erythropoeitic activity. Parameters
      available on the Sysmex XN analyzers include the percentage of microcytic red
      blood cells (%Micro-R), percentage of macrocytic red blood cells (%Macro-R),
      percentage of hypochromic red blood cells (%Hypo-He), percentage of hyperchromic
      red blood cells (%Hyper-He), reticulocyte hemoglobin content (Ret-He), and
      immature reticulocyte fraction (IRF). However, use of these parameters is limited
      by specimen stability. Methods: To verify the stability of the new erythrocyte
      and reticulocyte parameters during prolonged storage, 20 blood specimens were
      analyzed on the Sysmex XN-9000 hematology analyzer. The specimens included
      healthy patients (60%) and patients with anemia (40%). The specimens were stored
      at room temperature (RT) and at 4 degrees  to 8 degrees C. Analysis was performed
      after 12, 24, 48, and 72 hours of storage. Results: Reticulocyte parameters IRF
      and Ret-He were precise and stable for at least 72 hours after collection when
      stored at RT and 4 degrees  to 8 degrees C. The volume-dependent parameters,
      %Macro-R and %Micro-R, were stable for less than 12 hours after collection at RT
      (mean [SD%], 6.55 [3.19%] and -20.70 [10.37%], respectively). Storage at 4
      degrees  to 8 degrees C showed a reduction in osmotic swelling. However, %Macro-R
      and %Micro-R were stable for less than 12 hours after collection (mean [SD%],
      4.89 [2.02%] and -17.17 [8.38%], respectively). Similarly, %Hypo-He showed a mean
      (SD%) increase of 0.73 (4.05%) and %Hyper-He showed a decrease of -0.70 (9.72%)
      at less than 12 hours after storage at 4 degrees  to 8 degrees C. Conclusion: New
      reticulocyte parameters stored at RT and 4 degrees  to 8 degrees C are suitable
      for testing on the Sysmex XN analyzer.

PMID- 29365193
TI  - Prognostic value of coronary computed tomographic angiography findings in
      asymptomatic individuals: a 6-year follow-up from the prospective multicentre
      international CONFIRM study.
AB  - Aim: The long-term prognostic benefit of coronary computed tomographic
      angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic
      populations is unknown. Methods and results: From the prospective multicentre
      international CONFIRM long-term study, we evaluated asymptomatic subjects without
      known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n =
      1226). Coronary computed tomographic angiography findings included the severity
      of coronary artery stenosis, plaque composition, and coronary segment location.
      Using the C-statistic and likelihood ratio tests, we evaluated the incremental
      prognostic utility of CCTA findings over a base model that included a panel of
      traditional risk factors (RFs) as well as CACS to predict long-term all-cause
      mortality. During a mean follow-up of 5.9 +/- 1.2 years, 78 deaths occurred.
      Compared with the traditional RF alone (C-statistic 0.64), CCTA findings
      including coronary stenosis severity, plaque composition, and coronary segment
      location demonstrated improved incremental prognostic utility beyond traditional
      RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental chi2 range 20.7
      25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA
      findings when added to a base model containing both traditional RF and CACS (C
      statistics P > 0.05, for all). Conclusions: Coronary computed tomographic
      angiography improved prognostication of 6-year all-cause mortality beyond a set
      of conventional RF alone, although, no further incremental value was offered by
      CCTA when CCTA findings were added to a model incorporating RF and CACS.

PMID- 29365194
TI  - Delusion Proneness is Linked to a Reduced Usage of Prior Beliefs in Perceptual
      Decisions.
AB  - Predictive coding theories state an aberrant weighting of prior beliefs and
      present sensory information as a core computational pathology in psychosis.
      Specifically, it has been proposed that the influence of prior beliefs which
      attenuate improbable sensory information is weakened, resulting in an
      overweighing of this potentially misleading information. However, it is currently
      unclear whether this alteration is specific to perceptual processes or whether it
      represents a more pervasive deficit that extends to cognitive processes. Here, we
      carried out 2 behavioral experiments that probed the usage of priors during
      perceptual and cognitive processes, respectively, in 123 healthy individuals with
      varying degrees of delusion proneness. In an audio-visual perceptual
      discrimination task, participants had to judge the global motion direction of
      random dot kinematograms. Prior beliefs were induced by auditory cues that
      probabilistically predicted the global motion direction of the dot kinematograms,
      allowing us to measure the impact of prior beliefs on perceptual decision making.
      A control experiment paralleled the design of the perceptual decision making task
      in the domain of cognitive decision making. By fitting the participants'
      responses with a probabilistic decision model, we quantified the impact of prior
      beliefs on participants' decisions in both tasks. With growing delusion
      proneness, we found a decreased impact of prior beliefs on perceptual but not on
      cognitive decision making. Our results show that delusion proneness is linked to
      a specifically reduced usage of prior beliefs in perceptual decisions, thereby
      empirically substantiating predictive coding theories of psychosis.

PMID- 29365195
TI  - Estimation of broiler responses to increased dietary methionine hydroxy analogue
      [DL-2-hydroxy-(4-methylthio) butanoic acid] using linear and nonlinear regression
      models.
AB  - As the first limiting amino acid in corn-soy broiler diets, methionine (Met) is
      supplemented using commercial synthetic sources as demanded to obtain economic
      feed formulations. The Met analogue DL-2-hydroxy-4-(methylthio)-butanoic acid
      (HMTBA) is largely utilized with that objective. This study intended to obtain
      responses of broilers fed with increasing levels of HMTBA, from 28 to 42 d, such
      that economic returns can be calculated. A total of 2,106 Cobb * Cobb 500 one-day
      old male broilers was randomly placed in 81 floor pens (2.7 m2 each). Birds were
      fed conventional starter (zero to 14 d) and grower (14 to 28 d) diets. Starting
      at 28 d of age, pens of 26 birds were randomly allocated into 9 feed treatments
      with 9 replications having increasing supplementations with HMTBA (0.00, 0.07,
      0.14, 0.21, 0.28, 0.35, 0.42, 0.49 and 0.56%). These were prepared by mixing
      different proportions of corn-soy dilution and summit diets, which had the same
      formulated concentration of nutrients and energy [19.7% CP, 0.90% Ca, 0.45% Av.
      P, 0.95% digestible Lys, and 3,150 kcal/kg AMEn], with the exception of HMTBA
      [0.56% in the summit but not supplemented in the corn-soy dilution diet (0.52%
      digestible TSAA)]]. Growth performance was evaluated until 42 d when carcass
      yield and commercial cuts were evaluated using 6 birds randomly taken from each
      pen. Body weight gain (BWG), feed conversion ratio (FCR), proportion of breast
      fillets, and abdominal fat were adjusted using linear broken-line, exponential
      asymptotic and quadratic polynomial regression models (P < 0.05). Estimations of
      maximum responses for supplemented HMTBA by the linear broken-line model were
      0.17% for BWG, 0.14% for FCR, and 0.29% for breast fillets. Using exponential and
      quadratic regressions, optimized HMTBA supplementations were obtained at 0.34 and
      0.35% for BWG, 0.20 and 0.33% for FCR, and 0.31 and 0.36% for breast fillets,
      respectively. Supplemental levels of HMTBA that optimize growth performance and
      breast meat in male broilers from 28 to 42 d, using different regression models,
      varied from 0.14 to 0.36%.

PMID- 29365196
TI  - Effect of Antenatal Steroids on Respiratory Morbidity of Late Preterm Newborns: A
      Randomized Controlled Trial.
AB  - Objective: The objective of this article was to study the effect of antenatal
      dexamethasone on the respiratory morbidity of late preterm newborns. Study
      design: A randomized controlled trial, conducted in Obstetrics and Gynecology
      Department in collaboration with Neonatology department at JIPMER, India. In
      total, 155 women were studied in each group. Intention to treat analysis and per
      protocol analysis were done. Results: Overall 31 (10%) newborns were admitted to
      intensive care unit. The composite respiratory morbidity (defined as respiratory
      distress syndrome and/or transient tachypnea of newborn) was observed in 64
      (41.6%) infants in the study and 56 (36.2%) infants in the control group. On
      multivariable-adjusted analysis, use of steroids was not found to be associated
      with decrease in composite respiratory morbidity [adjusted relative risk 0.91
      (95% confidence interval: 0.7-1.2)]. Conclusions: Antenatal dexamethasone does
      not reduce the composite respiratory morbidity of babies born vaginally or by
      emergency cesarean to women with late preterm labor.

PMID- 29365197
TI  - Salicylic Acid and Jasmonic Acid Pathways are Activated in Spatially Different
      Domains Around the Infection Site During Effector-Triggered Immunity in
      Arabidopsis thaliana.

PMID- 29365198
TI  - Altered Functional Connectivity of the Default Mode Network in Patients With
      Schizo-obsessive Comorbidity: A Comparison Between Schizophrenia and Obsessive
      compulsive Disorder.
AB  - Clinical and neuroimaging data support the idea that schizo-obsessive comorbidity
      (SOC), similar to obsessive-compulsive disorder (OCD) and schizophrenia (SCZ),
      may be a distinct brain disorder. In this study, we examined the strength of
      resting-state functional connectivity (rsFC) between 19 subregions of the default
      mode network (DMN) and whole brain voxels in 22 patients with SOC features, 20
      patients with SCZ alone, 22 patients with OCD, and 22 healthy controls (HC). The
      main results demonstrated that patients with SOC exhibited the highest rsFC
      strength within subregions of the DMN and the lowest rsFC strength between the
      DMN and subregions of the salience network (SN) compared with the other 3 groups.
      In addition, compared with HCs, all 3 patient groups exhibited increased rsFC
      between subregions of the DMN and the executive control network (ECN). The SOC
      and SCZ group both exhibited increased rsFC between subregions of the DMN and the
      middle temporal gyrus, but the OCD group exhibited decreased rsFC between them.
      These findings highlight a specific alteration in functional connectivity in the
      DMN in patients with SOC, and provide new insights into the dysfunctional brain
      organization of different mental disorders.

PMID- 29365201
TI  - International Cognition and Cancer Task Force Recommendations for Neuroimaging
      Methods in the Study of Cognitive Impairment in Non-CNS Cancer Patients.
AB  - Cancer- and treatment-related cognitive changes have been a focus of increasing
      research since the early 1980s, with meta-analyses demonstrating poorer
      performance in cancer patients in cognitive domains including executive
      functions, processing speed, and memory. To facilitate collaborative efforts, in
      2011 the International Cognition and Cancer Task Force (ICCTF) published
      consensus recommendations for core neuropsychological tests for studies of cancer
      populations. Over the past decade, studies have used neuroimaging techniques,
      including structural and functional magnetic resonance imaging (fMRI) and
      positron emission tomography, to examine the underlying brain basis for cancer-
      and treatment-related cognitive declines. As yet, however, there have been no
      consensus recommendations to guide researchers new to this field or to promote
      the ability to combine data sets. We first discuss important methodological
      issues with regard to neuroimaging study design, scanner considerations, and
      sequence selection, focusing on concerns relevant to cancer populations. We
      propose a minimum recommended set of sequences, including a high-resolution T1
      weighted volume and a resting state fMRI scan. Additional advanced imaging
      sequences are discussed for consideration when feasible, including task-based
      fMRI and diffusion tensor imaging. Important image data processing and analytic
      considerations are also reviewed. These recommendations are offered to facilitate
      increased use of neuroimaging in studies of cancer- and treatment-related
      cognitive dysfunction. They are not intended to discourage investigator-initiated
      efforts to develop cutting-edge techniques, which will be helpful in advancing
      the state of the knowledge. Use of common imaging protocols will facilitate
      multicenter and data-pooling initiatives, which are needed to address critical
      mechanistic research questions.

PMID- 29365200
TI  - Effects of supplementation with vegetable oils, including castor oil, on milk
      production of ewes and on growth of their lambs.
AB  - The objectives in this experiment were to compare the effects of castor oil,
      canola oil, or sunflower oil on lactation performance, milk composition, and milk
      fatty acid (FA) profile in Santa Ines ewes and on growth of lambs. Forty-four
      ewes (66.9 +/- 4.7 kg of initial BW, mean +/- SD) were penned individually with
      their lambs and used in a randomized complete block design with 11 blocks and
      four diets. The experimental diets were as follows: 1) basal diet without added
      oil (control), 2) 30 g FA/kg DM of canola oil (CAN), 3) 30 g FA/kg DM of
      sunflower oil (SUN), and 4) 30 g FA/kg DM of castor oil (CAS). The oils were
      added to a basal diet containing 50% of roughage. Once a week, from the 2nd to
      8th wk of lactation, ewes were separated from their lambs, injected with
      oxytocin, and mechanically milked to empty the udder. After 3 h, using the same
      procedure, milk production was recorded, and milk was sampled for composition and
      FA profile determination. The growth of the lambs was monitored weekly. Ewes fed
      the control diet had greater (P < 0.05) dry matter intake (DMI) than those fed
      the oil-supplemented diets. No effect was observed on milk yield and on final BW
      of lambs. Milk fat and milk total solid concentrations were greater (P < 0.05)
      with the supply of CAS. Supplementation with CAN and SUN, but not with CAS,
      reduced (P < 0.05) the sum of FA with 14 or less carbon chains and increased (P <
      0.05) the c9-18:1, 18:0 and most of the biohydrogenation intermediates, including
      the t10-18:1, t11-18:1, and c9,t11-18:2. All oil-supplemented diets reduced (P <
      0.05) the content of 16:0 when compared with the control. Milk from ewes fed CAS
      presented only small proportion of 12-OH,c9-18:1 (0.31% of total FA) but much
      larger proportions of 12-OH-18:0 (1.58% of total FA) and particularly of 12-oxo
      18:0 (2.95 % of total FA), which suggests that 12-OH,c9-18:1 was extensively
      metabolized in the rumen. Concluding, CAS increased milk fat and modified the
      milk FA composition by increasing the hydroxy- and oxo-FA. The potential health
      promoting proprieties and technological advantages of milk enriched with hydroxy-
      and oxo-FA are not know at present but deserve to be explored.

PMID- 29365202
TI  - Pediatric low-grade gliomas: a brave new world.

PMID- 29365199
TI  - Neurobiological correlates of emotional intelligence in voice and face perception
      networks.
AB  - Facial expressions and voice modulations are among the most important
      communicational signals to convey emotional information. The ability to correctly
      interpret this information is highly relevant for successful social interaction
      and represents an integral component of emotional competencies that have been
      conceptualized under the term emotional intelligence. Here, we investigated the
      relationship of emotional intelligence as measured with the Salovey-Caruso
      Emotional-Intelligence-Test (MSCEIT) with cerebral voice and face processing
      using functional and structural magnetic resonance imaging. MSCEIT scores were
      positively correlated with increased voice-sensitivity and gray matter volume of
      the insula accompanied by voice-sensitivity enhanced connectivity between the
      insula and the temporal voice area, indicating generally increased salience of
      voices. Conversely, in the face processing system, higher MSCEIT scores were
      associated with decreased face-sensitivity and gray matter volume of the fusiform
      face area. Taken together, these findings point to an alteration in the balance
      of cerebral voice and face processing systems in the form of an attenuated face
      vs-voice bias as one potential factor underpinning emotional intelligence.

PMID- 29365203
TI  - Meeting Update-Society for Neuro-Oncology 2017 Annual Meeting.

PMID- 29365204
TI  - Ritanserin, a novel agent targeting the mesenchymal subtype of glioblastomas.

PMID- 29365205
TI  - The siren song of bevacizumab: swan song or clarion call?

PMID- 29365206
TI  - Leg movement activity during sleep in school-age children and adolescents: a
      detailed study in normal controls and participants with restless legs syndrome
      and narcolepsy type 1.
AB  - Study Objectives: To evaluate leg movement activity during sleep (LMS) in normal
      school-age children and adolescents, to eventually establish age-specific
      periodic LMS (PLMS) index thresholds that support the diagnosis of restless legs
      syndrome (RLS), and to evaluate the utility of other LMS indices. Methods:
      Polysomnographic recordings from 61 controls, 46 children with RLS, and 44
      children with narcolepsy type 1 (NT1) were analyzed for total leg movements
      (LMS), PLMS, and isolated leg movements (ISOLMS) duration and indices, separately
      for school-age children and adolescents. Moreover, intermovement interval (IMI)
      graphs and time-of-night distribution of LMS were analyzed, and cut-off
      thresholds for PLMS index and total LMS index were assessed for the separation of
      RLS from controls. Results: All indices tended to decrease from school-age
      children to adolescents in normal controls and in NT1, whereas in RLS, only PLMS
      index increased. All school-age children had a similar IMI distribution with a
      single peak at IMI 2-4 s followed by gradual decline. In adolescents with RLS, a
      second peak at IMI 10-50 s was seen. Time-of-night distribution of most indices
      decreased in RLS, whereas most tended to increase in NT1. A PLMS index cutoff of
      2 per hour best differentiated RLS from controls in school-age children (accuracy
      70.0%) and in adolescents (accuracy 70.8%); however, most participants with NT1
      also showed PLMS indices higher than this threshold. Conclusions: PLMS index
      alone does not reliably predict the diagnosis of RLS in children and adolescents.
      However, analyses of IMI distribution and time-of-night distribution provide
      additional elements to support a diagnosis of RLS.

PMID- 29365207
TI  - Effects of maternal dietary canthaxanthin and 25-hydroxycholecalciferol
      supplementation on antioxidant status and calcium-phosphate metabolism of progeny
      ducks.
AB  - Three experiments were conducted to investigate the effects of maternal dietary
      canthaxanthin (CX) and 25-hydroxycholecalciferol (25-OH-D3) supplementation on
      antioxidant status and calcium-phosphate metabolism of progeny ducks. Cherry
      Valley duck breeders (38 wk old) were fed either a control diet or the same diet
      plus CX (6 mg/kg) and 25-OH-D3 (0.069 mg/kg) for 32 weeks. Experiments 1, 2, and
      3 were conducted with progeny ducks hatched from eggs laid by duck breeder hens
      at 54, 62, and 70 wk of age, respectively. Progeny ducks from both maternal
      treatments were fed with the same NRC (1994) vitamin regimen starter (1 to 14 d)
      and finisher (15 to 35 d) diets in experiments 1 and 2, and fed with the same
      high vitamin regimen starter (1 to 14 d) and finisher (15 to 35 d) diets in
      experiments 3. High vitamin regimen had higher levels of all vitamins, except
      biotin, than the NRC (1994) vitamin regimen. In experiment 1, maternal CX and 25
      OH-D3 increased (P < 0.05) shank pigmentation and tibiotarsus ash and tended to
      decrease (P < 0.1) liver total superoxide dismutase activity (T-SOD) of one-day
      old progeny ducks; and increased (P < 0.05) shank pigmentation, decreased (P =
      0.05) liver protein carbonyl, and tended to increase (P < 0.1) liver total
      antioxidant capacity (T-AOC) of 14-day-old progeny ducks. In experiment 2,
      maternal CX and 25-OH-D3 increased (P < 0.05) shank pigmentation and liver T-AOC
      and decreased (P < 0.05) liver protein carbonyl of one-day-old progeny ducks, but
      increased (P < 0.05) the serum phosphate level of 14-day-old progeny ducks. In
      experiment 3, maternal CX and 25-OH-D3 increased (P < 0.05) shank pigmentation of
      one-, 14-, and 35-day-old progeny ducks and tended to increase (P < 0.1) liver T
      SOD and tibiotarsus ash, but decrease (P < 0.1) liver malondialdehyde of one-day
      old progeny ducks. It can be concluded that progeny dietary high vitamin regimen
      could partially prevent maternal CX-derived progeny shank pigmentation from
      bleaching. Maternal CX- and 25-OH-D3-derived effects are influenced by the hen's
      age and progeny's dietary vitamin regimen.

PMID- 29365208
TI  - Salmonella isolated from chicken carcasses from a slaughterhouse in the state of
      Mato Grosso, Brazil: antibiotic resistance profile, serotyping, and
      characterization by repetitive sequence-based PCR system.
AB  - Salmonella is one of the major causative agents of foodborne infections.
      Salmonellosis becomes more dangerous when strains resistant to several
      antibiotics are found in food, especially in chicken, one of the primary
      transmission vehicles of this pathogen for humans. The present study aimed to
      estimate the occurrence of Salmonella in chicken carcasses from the state of Mato
      Grosso, Brazil, as well as determine the antibiotic resistance profile and
      genotypic characteristic of multi-drug resistant (MDR) isolates. During a 15
      month period, from 01/2014 to 05/2015, 850 samples of chilled fresh chicken
      carcasses were sampled from a slaughterhouse and submitted to Salmonella
      determinations according to the ISO-6579/2002 method, serotyping and multiplex
      PCR. The disc diffusion test was applied for 17 antibiotics, according to CLSI
      (2014). Five isolates were genotyped by repetitive sequence-based PCR using the
      semi-automated DiversiLab (bioMerieux(r)) system. The occurrence of Salmonella in
      chicken carcasses was of 3.7% (31/850), with only 4 strains (12.9%) presenting as
      MDR, and 6 strains (19.35%) displaying ESBL. The predominant serovars were
      Salmonella Infantis (35.4%, 11/31), and S. Abony (25.8%, 8/31), followed by
      serovars S. Agona (12.9%, 4/31), S. Schwarzengrund (9.7%, 3/31), S. Anatum and
      Salmonella enterica O:4,5 (6.5%, 2/31), and only one Salmonella enterica O:6,7
      strain (3.2%, 1/31). All isolates were resistant to one to 5 classes of
      antibiotics in decreasing order: folate pathway inhibitors, beta-lactams
      (cephalosporins, penicillin, monobactams), tetracyclines, chloramphenicol, and
      gentamicin. However, strains sensitive to florfenicol, streptomycin, nalidixic
      acid, ciprofloxacin, enrofloxacin, and nitrofurantoin were also found in this
      study. Genotyping revealed 98 to 99% homology between 3 Salmonella strains, which
      displayed high phenotypic resistance similarity to beta-lactams and folate
      pathway inhibitors. Detection of MDR non-typhoid Salmonella in chicken
      slaughterhouses with quality assurance systems such as Hazard Analysis and
      Critical Points and Implemented Good Manufacturing Practices is a concern,
      reinforcing the need for constant monitoring of these pathogens, with the purpose
      of safeguarding the safety of their products.

PMID- 29365209
TI  - The dynamic life of arbuscular mycorrhizal fungal symbionts.

PMID- 29365210
TI  - Impact of priming on global soil carbon stocks.
AB  - Fresh carbon input (above and belowground) contributes to soil carbon
      sequestration, but also accelerates decomposition of soil organic matter through
      biological priming mechanisms. Currently, poor understanding precludes the
      incorporation of these priming mechanisms into the global carbon models used for
      future projections. Here, we show that priming can be incorporated based on a
      simple equation calibrated from incubation and verified against independent
      litter manipulation experiments in the global land surface model, ORCHIDEE. When
      incorporated into ORCHIDEE, priming improved the model's representation of global
      soil carbon stocks and decreased soil carbon sequestration by 51% (12 +/- 3 Pg C)
      during the period 1901-2010. Future projections with the same model across the
      range of CO2 and climate changes defined by the IPCC-RCP scenarios reveal that
      priming buffers the projected changes in soil carbon stocks - both the increases
      due to enhanced productivity and new input to the soil, and the decreases due to
      warming-induced accelerated decomposition. Including priming in Earth system
      models leads to different projections of soil carbon changes, which are
      challenging to verify at large spatial scales.

PMID- 29365212
TI  - Iodine(III) Derivatives as Halogen Bonding Organocatalysts.
AB  - Hypervalent iodine(III) derivatives are known as versatile reagents in organic
      synthesis, but there is only one previous report on their use as Lewis acidic
      organocatalysts. Herein, we present first strong indications for the crucial role
      of halogen bonding in this kind of catalyses. To this end, the solvolysis of
      benzhydryl chloride and the Diels-Alder reaction of cyclopentadiene with methyl
      vinyl ketone served as benchmark reactions for halide abstraction and the
      activation of neutral compounds. Iodolium compounds (cyclic diaryl iodonium
      species) were used as activators or catalysts, and we were able to markedly
      reduce or completely switch off their activity by sterically blocking one or two
      of their electrophilic axes. Compared with previously established bidentate
      cationic halogen bond donors, the monodentate organoiodine derivatives used
      herein are at least similarly active (in the Diels-Alder reaction) or even
      decidedly more active (in benzhydryl chloride solvolysis).

PMID- 29365211
TI  - Yeasts of the soil - obscure but precious.
AB  - Pioneering studies performed in the nineteenth century demonstrated that yeasts
      are present in below-ground sources. Soils were regarded more as a reservoir for
      yeasts that reside in habitats above it. Later studies showed that yeast
      communities in soils are taxonomically diverse and different from those above
      ground. Soil yeasts possess extraordinary adaptations that allow them to survive
      in a wide range of environmental conditions. A few species are promising sources
      of yeast oils and have been used in agriculture as potential antagonists of soil
      borne plant pathogens or as plant growth promoters. Yeasts have been studied
      mainly in managed soils such as vineyards, orchards and agricultural fields, and
      to a lesser extent under forests and grasslands. Our knowledge of soil yeasts is
      further biased towards temperate and boreal forests, whereas data from Africa,
      the Americas and Asia are scarce. Although soil yeast communities are often
      species-poor in a single sample, they are more diverse on the biotope level. Soil
      yeasts display pronounced endemism along with a surprisingly high proportion of
      currently unidentified species. However, like other soil inhabitants, yeasts are
      threatened by habitat alterations owing to anthropogenic activities such as
      agriculture, deforestation and urbanization. In view of the rapid decline of many
      natural habitats, the study of soil yeasts in undisturbed or low-managed biotopes
      is extremely valuable. The purpose of this review is to encourage researchers,
      both biologists and soil scientists, to include soil yeasts in future studies.

PMID- 29365213
TI  - Tailored Organic Electrode Material Compatible with Sulfide Electrolyte for
      Stable All-Solid-State Sodium Batteries.
AB  - All-solid-state sodium batteries (ASSSBs) with nonflammable electrolytes and
      ubiquitous sodium resource are a promising solution to the safety and cost
      concerns for lithium-ion batteries. However, the intrinsic mismatch between low
      anodic decomposition potential of superionic sulfide electrolytes and high
      operating potentials of sodium-ion cathodes leads to a volatile cathode
      electrolyte interface and undesirable cell performance. Here we report a high
      capacity organic cathode, Na4 C6 O6 , that is chemically and electrochemically
      compatible with sulfide electrolytes. A bulk-type ASSSB shows high specific
      capacity (184 mAh g-1 ) and one of the highest specific energies (395 Wh kg-1 )
      among intercalation compound-based ASSSBs. The capacity retentions of 76 % after
      100 cycles at 0.1 C and 70 % after 400 cycles at 0.2 C represent the record
      stability for ASSSBs. Additionally, Na4 C6 O6 functions as a capable anode
      material, enabling a symmetric all-organic ASSSB with Na4 C6 O6 as both cathode
      and anode materials.

PMID- 29365214
TI  - Reaction Pathway Dependence in Plasmonic Catalysis: Hydrogenation as a Model
      Molecular Transformation.
AB  - The localized surface plasmon resonance (LSPR) excitation in plasmonic
      nanoparticles can enhance or mediate chemical transformations. Increased reaction
      rates for several reactions have been reported due to this phenomenon; however,
      the fundamental understanding of mechanisms and factors that affect activities
      remains limited. Here, by investigating hydrogenation reactions as a model
      transformation and employing different reducing agents, H2 and NaBH4 , which led
      to different hydrogenation reaction pathways, we observed that plasmonic
      excitation of Au nanoparticle catalysts can lead to negative effects over the
      activities. The underlying physical reason was explored using density functional
      theory calculations. We observed that positive versus negative effects on the
      plasmonic catalytic activity is reaction-pathway dependent. These results shed
      important insights on our current understanding of plasmonic catalysis,
      demonstrating reaction pathways must be taken into account for the design of
      plasmonic nanocatalysts.

PMID- 29365215
TI  - Single-Molecule Determination of the Isomers of d-Glucose and d-Fructose that
      Bind to Boronic Acids.
AB  - Monosaccharides, such as d-glucose and d-fructose, exist in aqueous solution as
      an equilibrium mixture of cyclic isomers and can be detected with boronic acids
      by the reversible formation of boronate esters. The engineering of accurate,
      discriminating and continuous monitoring devices relies on knowledge of which
      cyclic isomer of a sugar binds to a boronic acid receptor. Herein, by monitoring
      fluctuations in ionic current, we show that an engineered alpha-hemolysin
      (alphaHL) nanopore modified with a boronic acid reacts reversibly with d-glucose
      as the pyranose isomer (alpha-d-glucopyranose) and d-fructose as either the
      furanose (beta-d-fructofuranose) or the pyranose (beta-d-fructopyranose). Both of
      these binding modes contradict current binding models. With this knowledge, we
      distinguished the individual sugars in a mixture of d-maltose, d-glucose, and d
      fructose.

PMID- 29365216
TI  - Insight into Metal Removal from Peptides that Sequester Copper for Methane
      Oxidation.
AB  - Methanobactins (Mbns) are modified peptides that sequester copper (Cu)
      methanotrophs use to oxidize methane. Limited structural information is available
      for this class of natural products, as is an understanding of how cells are able
      to utilize Mbn-bound Cu. The crystal structure of Methylosinus sporium NR3K CuI 
      Mbn provides further information about the structural diversity of Mbns and the
      first insight into their Cu-release mechanism. Nitrogen ligands from oxazolone
      and pyrazinediol rings chelate CuI along with adjacent coordinating sulfurs from
      thioamides. In vitro solution data are consistent with a CuI -Mbn monomer as
      found for previously characterized Mbns. In the crystal structure, the N-terminal
      region has undergone a conformational change allowing the formation of a CuI2 
      Mbn2 dimer with CuI sites bound by chelating units from adjacent chains. Such a
      structural alteration will facilitate CuI release from Mbns.

PMID- 29365220
TI  - H. pylori Infection: ACG Updates Treatment Recommendations.

PMID- 29365221
TI  - Colorectal Cancer Screening and Surveillance in Individuals at Increased Risk.
AB  - Individuals at increased risk of developing colorectal cancer include those with
      a personal or family history of advanced adenomas or colorectal cancer, a
      personal history of inflammatory bowel disease, or genetic polyposis syndromes.
      In general, these persons should undergo more frequent or earlier testing than
      individuals at average risk. Individuals who have a first-degree relative with
      colorectal cancer or advanced adenoma diagnosed before 60 years of age or two
      first-degree relatives diagnosed at any age should be advised to start screening
      colonoscopy at 40 years of age or 10 years younger than the earliest diagnosis in
      their family, whichever comes first. In individuals with ulcerative colitis or
      Crohn disease with colonic involvement, colonoscopy should begin eight to 10
      years after the onset of symptoms and be repeated every one to three years.
      Individuals who have a first-degree relative with hereditary nonpolyposis
      colorectal cancer should begin colonoscopy at 25 years of age and repeat
      colonoscopy every one to two years. In persons with a family history of
      adenomatous polyposis syndromes, screening should begin at 10 years of age or in
      a person's mid-20s, depending on the syndrome; repeat colonoscopy is typically
      required every one to two years. Screening colonoscopy should begin at eight
      years of age in individuals with Peutz-Jeghers syndrome. If results are normal,
      colonoscopy can be repeated at 18 years of age and then every three years.
      Persons with sessile serrated adenomatous polyposis should begin annual
      colonoscopy as soon as the diagnosis is established.

PMID- 29365222
TI  - Heel Pain: Diagnosis and Management.
AB  - The differential diagnosis of heel pain is extensive, but a mechanical etiology
      is the most common. The specific anatomic location of the pain can help guide
      diagnosis. The most common diagnosis is plantar fasciitis, which leads to medial
      plantar heel pain, especially with the first weight-bearing steps after rest.
      Other causes of plantar heel pain include calcaneal stress fractures
      (progressively worsening pain after an increase in activity or change to a harder
      walking surface), nerve entrapment or neuroma (pain accompanied by burning,
      tingling, or numbness), heel pad syndrome (deep, bruise-like pain in the middle
      of the heel), and plantar warts. Achilles tendinopathy is a common cause of
      posterior heel pain; other tendinopathies result in pain localized to the
      insertion site of the affected tendon. Posterior heel pain can also be attributed
      to Haglund deformity (a prominence of the calcaneus that may lead to
      retrocalcaneal bursa inflammation) or Sever disease (calcaneal apophysitis common
      in children and adolescents). Medial midfoot heel pain, particularly with
      prolonged weight bearing, may be due to tarsal tunnel syndrome, which is caused
      by compression of the posterior tibial nerve. Sinus tarsi syndrome manifests as
      lateral midfoot heel pain and a feeling of instability, particularly with
      increased activity or walking on uneven surfaces.

PMID- 29365223
TI  - Thirty Years of AFP: Having Fun Painting the Fence.

PMID- 29365217
TI  - Will imaging individual raphe nuclei in males with major depressive disorder
      enhance diagnostic sensitivity and specificity?
AB  - BACKGROUND: Positron emission tomography (PET) studies in major depressive
      disorder (MDD) have reported higher serotonin 1A (5-HT1A ) autoreceptor binding
      in the raphe. In males, the difference is so large that it can potentially be
      used as the first biological marker for MDD. However, the raphe includes several
      nuclei, which project to different regions of the brain and spinal cord and may
      be differentially involved in disease. We aimed to identify 5-HT1A differences in
      individual raphe nuclei using PET in order to determine whether use of subnuclei
      would provide greater sensitivity and specificity of diagnosing MDD. METHODS: We
      identified individual nuclei using a hybrid set-level technique on an average [11
      C]-WAY100635 PET image derived from 52 healthy volunteers (HV). We delineated
      three nuclei: dorsal raphe nucleus (DRN), median raphe nucleus (MRN), and raphe
      magnus (RMg). An atlas image of these nuclei was created and nonlinearly warped
      to each subject (through an associated MRI) in a separate sample of 41 males (25
      HV, 16 MDD) who underwent [11 C]-WAY100635 PET. RESULTS: 5-HT1A binding was
      elevated in DRN in MDD (P < .01), and was not different in the RMg and MRN
      between groups. Receiver operating characteristic (ROC) curves showed that
      combining DRN and MRN produces highest sensitivity (94%) and specificity (84%) to
      identify MDD. CONCLUSION: In agreement with postmortem studies, we found higher 5
      HT1A autoreceptor binding in MDD selectively in the DRN. 5-HT1A autoreceptor
      binding in the combined DRN and MRN is a better biomarker for MDD than in the
      raphe as a whole.

PMID- 29365224
TI  - Nebivolol/Valsartan (Byvalson) for Hypertension.

PMID- 29365227
TI  - Screening for Preeclampsia: Recommendation Statement.

PMID- 29365226
TI  - Noninfectious Penile Lesions.
AB  - Noninfectious penile lesions are classified by clinical presentation as
      papulosquamous (e.g., psoriasis), inflammatory (e.g., lichen sclerosus, lichen
      nitidus, lichen planus), vascular (e.g., angiokeratomas), or neoplastic (e.g.,
      carcinoma in situ, invasive squamous cell carcinoma). Psoriasis presents as red
      or salmon-colored plaques with overlying silvery scales, often with extragenital
      cutaneous lesions. Lichen sclerosus presents as a phimotic, hypopigmented prepuce
      or glans penis with a cellophane-like texture. Lichen nitidus usually produces
      asymptomatic pinhead-sized, hypopigmented papules. The lesions of lichen planus
      are pruritic, violaceous, polygonal papules that are typically systemic.
      Angiokeratomas are typically asymptomatic, well-circumscribed, red or blue
      papules, often with annular or figurate configurations. Carcinoma in situ should
      be suspected if there are velvety red or keratotic plaques on the glans penis or
      prepuce, whereas invasive squamous cell carcinoma presents as a painless lump,
      ulcer, or fungating mass. Some benign lesions, such as psoriasis and lichen
      planus, may mimic carcinoma in situ or invasive squamous cell carcinoma. Biopsy
      is indicated if the diagnosis is in doubt or neoplasm cannot be excluded. The
      management of benign noninfectious penile lesions usually involves observation,
      topical corticosteroids, or topical calcineurin inhibitors. Neoplastic lesions
      generally warrant organ-sparing surgery.

PMID- 29365228
TI  - Screening for Preeclampsia.

PMID- 29365230
TI  - Tuberculosis: Guidelines for Diagnosis from the ATS, IDSA, and CDC.

PMID- 29365229
TI  - Abrupt Onset of a Tender Rash on the Upper and Lower Extremities.

PMID- 29365231
TI  - Long-Term Use of Bisphosphonates Increases the Risk of Fractures in Older Women.

PMID- 29365232
TI  - Delayed Antibiotic Prescription for New-Onset Cough Associated with Decreased
      Reconsulatation.

PMID- 29365233
TI  - Ear Pain: Diagnosing Common and Uncommon Causes.
AB  - Otalgia (ear pain) is a common presentation in the primary care setting with many
      diverse causes. Pain that originates from the ear is called primary otalgia, and
      the most common causes are otitis media and otitis externa. Examination of the
      ear usually reveals abnormal findings in patients with primary otalgia. Pain that
      originates outside the ear is called secondary otalgia, and the etiology can be
      difficult to establish because of the complex innervation of the ear. The most
      common causes of secondary otalgia include temporomandibular joint syndrome and
      dental infections. Primary otalgia is more common in children, whereas secondary
      otalgia is more common in adults. History and physical examination usually lead
      to the underlying cause; however, if the diagnosis is not immediately clear, a
      trial of symptomatic treatment, imaging studies, and consultation may be
      reasonable options. Otalgia may be the only presenting symptom in several serious
      conditions, such as temporal arteritis and malignant neoplasms. When risk factors
      for malignancy are present (e.g., smoking, alcohol use, diabetes mellitus, age 50
      years or older), computed tomography, magnetic resonance imaging, or
      otolaryngology consultation may be warranted.

PMID- 29365234
TI  - Effectiveness of Moisturizers in the Treatment of Patients with Eczema.

PMID- 29365235
TI  - Female Genital Mutilation or Cutting.

PMID- 29365236
TI  - Burning on the Tip of the Tongue.

PMID- 29365237
TI  - Intensive Blood Pressure Control in Older Patients Can Decrease Renal Function.

PMID- 29365238
TI  - Immediate Postpartum LARC: An Underused Contraceptive Option.

PMID- 29365240
TI  - Type 2 Diabetes Mellitus: Outpatient Insulin Management.
AB  - In patients with type 2 diabetes mellitus, insulin may be used to augment therapy
      with oral glycemic medications or as insulin replacement therapy. The American
      Diabetes Association suggests the use of long-acting (basal) insulin to augment
      therapy with one or two oral agents or one oral agent plus a glucagon-like
      peptide 1 receptor agonist when the A1C level is 9% or more, especially if the
      patient has symptoms of hyperglycemia or catabolism. Insulin regimens should be
      adjusted every three or four days until targets of self-monitored blood glucose
      levels are reached. A fasting and premeal blood glucose goal of 80 to 130 mg per
      dL and a two-hour postprandial goal of less than 180 mg per dL are recommended.
      Insulin use is associated with hypoglycemia and weight gain. Insulin analogues
      are as effective as human insulin at lowering A1C levels with lower risk of
      hypoglycemia, but they have significantly higher cost. Patients with one or more
      episodes of severe hypoglycemia (i.e., requiring assistance from others for
      treatment) may benefit from a short-term relaxation of glycemic targets. Several
      new insulin formulations have been approved recently that are associated with
      less risk of hypoglycemia compared with older formulations. The goals of therapy
      should be individualized based on many factors, including age, life expectancy,
      comorbid conditions, duration of diabetes, risk of hypoglycemia, cost, patient
      motivation, and quality of life.

PMID- 29365241
TI  - Pityriasis Rosea: Diagnosis and Treatment.
AB  - Pityriasis rosea is a common self-limiting rash that usually starts with a herald
      patch on the trunk and progresses along the Langer lines to a generalized rash
      over the trunk and limbs. The diagnosis is based on clinical and physical
      examination findings. The herald patch is an erythematous lesion with an elevated
      border and depressed center. The generalized rash usually presents two weeks
      after the herald patch. Patients can develop general malaise, fatigue, nausea,
      headaches, joint pain, enlarged lymph nodes, fever, and sore throat before or
      during the course of the rash. The differential diagnosis includes secondary
      syphilis, seborrheic dermatitis, nummular eczema, pityriasis lichenoides
      chronica, tinea corporis, viral exanthems, lichen planus, and pityriasis rosea
      like eruption associated with certain medications. Treatment is aimed at
      controlling symptoms and consists of corticosteroids or antihistamines. In some
      cases, acyclovir can be used to treat symptoms and reduce the length of disease.
      Ultraviolet phototherapy can also be considered for severe cases. Pityriasis
      rosea during pregnancy has been linked to spontaneous abortions.

PMID- 29365242
TI  - Dietary Interventions for Recurrent Abdominal Pain in Childhood.

PMID- 29365243
TI  - Stents for Stable Coronary Artery Disease.

PMID- 29365244
TI  - Oral Steroids Not Helpful for Acute Lower Respiratory Tract Infection in
      Nonasthmatic Adults.

PMID- 29365245
TI  - Young Febrile Infants: Step-by-Step Evaluation.

PMID- 29365246
TI  - Discuss Oral Health with All Women of Child-Bearing Age.

PMID- 29365247
TI  - Medications to Treat Obesity Lack Patient-Oriented Evidence.

PMID- 29365248
TI  - Pityriasis Rosea.

PMID- 29365249
TI  - Toward a Microparticle-Based System for Pooled Assays of Small Molecules in
      Cellular Contexts.
AB  - Experimental approaches to the discovery of small molecule probes and drug
      candidates often use biochemical or cell-based screening of large libraries
      (>105) of small molecules. Small molecules of interest are tested one at a time
      in individual wells of a microtiter plate, at a significant cost in time and
      resources. Furthermore, evaluation of large numbers of compounds in such assays
      requires robust cellular or biochemical screening formats that may not be
      relevant to the contexts found in human patients. We envision a solution to these
      issues that involves a pooled system of small molecule screening, which would
      require development of numerous new technologies, and solutions to several key
      challenges. We report here that a microparticle-based screening system can allow
      for screening of small molecules in such a pooled fashion, analogous to the
      pooled screens of genetic reagents that have been powerfully deployed in recent
      years. We developed a cleavable linker that can link small molecules of interest
      to silica microparticle beads, a DNA tag encoding the identity of the small
      molecule on each bead that was attached to the silica beads through a
      photocleavable linker to enable its amplification, and a bead-based fluorescent
      sensor that can report on the activity of small molecules in cells. We suggest
      that this pooled small molecule screening system could ultimately be useful for
      drug and probe discovery, allowing rapid and inexpensive screening of small
      molecules in assays of relevance to human diseases.

PMID- 29365250
TI  - Proteolytic Nanoparticles Replace a Surgical Blade by Controllably Remodeling the
      Oral Connective Tissue.
AB  - Surgical blades are common medical tools. However, blades cannot distinguish
      between healthy and diseased tissue, thereby creating unnecessary damage,
      lengthening recovery, and increasing pain. We propose that surgical procedures
      can rely on natural tissue remodeling tools-enzymes, which are the same tools our
      body uses to repair itself. Through a combination of nanotechnology and a
      controllably activated proteolytic enzyme, we performed a targeted surgical task
      in the oral cavity. More specifically, we engineered nanoparticles that contain
      collagenase in a deactivated form. Once placed at the surgical site, collagenase
      was released at a therapeutic concentration and activated by calcium, its
      biological cofactor that is naturally present in the tissue. Enhanced periodontal
      remodeling was recorded due to enzymatic cleavage of the supracrestal collagen
      fibers that connect the teeth to the underlying bone. When positioned in their
      new orientation, natural tissue repair mechanisms supported soft and hard tissue
      recovery and reduced tooth relapse. Through the combination of nanotechnology and
      proteolytic enzymes, localized surgical procedures can now be less invasive.

PMID- 29365251
TI  - Highly Efficient All-Solution Processed Inverted Quantum Dots Based Light
      Emitting Diodes.
AB  - In all-solution processed inverted quantum dots based light emitting diodes
      (QLEDs), the solvent erosion on the quantum dot (QD) layer prevents devices from
      reaching high performance. By employing an orthogonal solvent 1,4-dioxane for the
      hole transport layer (HTL) poly(9-vinlycarbazole) (PVK), the external quantum
      efficiencies (EQE) of red QLED is increased 4-fold, while the luminous
      efficiencies (LE) of blue QLED is enhanced by 25 times, compared to the previous
      devices' record. To further improve the device efficiency and reduce the
      efficiency roll-off, solution processed PVK/poly [(9,9-dioctylfluorenyl-2,7-diyl)
      co-(4,4'-(N-(p-butylphenyl))diphenylamine)] (TFB) double-layer HTL is introduced
      to facilitate hole injection with stepwise energy level. By reducing the hole
      injection barrier, the turn-on voltage of QLEDs decreases from 3.4 to 2.7 V for
      red, from 5.1 to 2.7 V for green, and from 5.3 to 4.1 V for blue. The peak LE
      reach 22.1 cd/A, 21.4 cd/A, and 1.99 cd/A, while the maximum EQE reach 12.7%,
      5.29%, and 5.99%, for red, green, and blue QLEDs, respectively. To the best of
      our knowledge, the red and blue QLEDs exhibit the best device performance among
      all the all-solution processed inverted QLEDs. In addition, the blue QLED is the
      champion among all the inverted QLEDs, including the devices fabricated by
      thermal evaporation.

PMID- 29365252
TI  - Room-Temperature Lasing from Monolithically Integrated GaAs Microdisks on
      Silicon.
AB  - Additional functionalities on semiconductor microchips are progressively
      important in order to keep up with the ever-increasing demand for more powerful
      computational systems. Monolithic III-V integration on Si promises to merge
      mature Si CMOS processing technology with III-V semiconductors possessing
      superior material properties, e. g., in terms of carrier mobility or band
      structure (direct band gap). In particular, Si photonics would strongly benefit
      from an integration scheme for active III-V optoelectronic devices in order to
      enable low-cost and power-efficient electronic-photonic integrated circuits. We
      report on room-temperature lasing from AlGaAs/GaAs microdisk cavities
      monolithically integrated on Si(001) using a selective epitaxial growth technique
      called template-assisted selective epitaxy. The grown gain material possesses
      high optical quality without indication of threading dislocations, antiphase
      boundaries, or twin defects. The devices exhibit single-mode lasing at T < 250 K
      and lasing thresholds between 2 and 18 pJ/pulse depending on the cavity size (1-3
      MUm in diameter).

PMID- 29365253
TI  - Structural Directed Growth of Ultrathin Parallel Birnessite on beta-MnO2 for High
      Performance Asymmetric Supercapacitors.
AB  - Two-dimensional birnessite has attracted attention for electrochemical energy
      storage because of the presence of redox active Mn4+/Mn3+ ions and spacious
      interlayer channels available for ions diffusion. However, current strategies are
      largely limited to enhancing the electrical conductivity of birnessite. One key
      limitation affecting the electrochemical properties of birnessite is the poor
      utilization of the MnO6 unit. Here, we assemble beta-MnO2/birnessite core-shell
      structure that exploits the exposed crystal face of beta-MnO2 as the core and
      ultrathin birnessite sheets that have the structure advantage to enhance the
      utilization efficiency of the Mn from the bulk. Our birnessite that has sheets
      parallel to each other is found to have unusual crystal structure with interlayer
      spacing, Mn(III)/Mn(IV) ratio and the content of the balancing cations differing
      from that of the common birnessite. The substrate directed growth mechanism is
      carefully investigated. The as-prepared core-shell nanostructures enhance the
      exposed surface area of birnessite and achieve high electrochemical performances
      (for example, 657 F g-1 in 1 M Na2SO4 electrolyte based on the weight of parallel
      birnessite) and excellent rate capability over a potential window of up to 1.2 V.
      This strategy opens avenues for fundamental studies of birnessite and its
      properties and suggests the possibility of its use in energy storage and other
      applications. The potential window of an asymmetric supercapacitor that was
      assembled with this material can be enlarged to 2.2 V (in aqueous electrolyte)
      with a good cycling ability.

PMID- 29365254
TI  - Multiple Hydrogen Bond Tethers for Grazing Formic Acid in Its Complexes with
      Phenylacetylene.
AB  - Complexes of phenylacetylene (PhAc) and formic acid (FA) present an interesting
      picture, where the two submolecules are tethered, sometimes multiply, by hydrogen
      bonds. The multiple tentacles adopted by PhAc-FA complexes stem from the fact
      that both submolecules can, in the same complex, serve as proton acceptors and/or
      proton donors. The acetylenic and phenyl pi systems of PhAc can serve as proton
      acceptors, while the =C-H or -C-H of the phenyl ring can act as a proton donor.
      Likewise, FA also is amphiprotic. Hence, more than 10 hydrogen-bonded structures,
      involving O-H...pi, C-H...pi, and C-H...O contacts, were indicated by our
      computations, some with multiple tentacles. Interestingly, despite the multiple
      contacts in the complexes, the barrier between some of the structures is small,
      and hence, FA grazes around PhAc, even while being tethered to it, with hydrogen
      bonds. We used matrix isolation infrared spectroscopy to experimentally study the
      PhAc-FA complexes, with which we located global and a few local minima, involving
      primarily an O-H...pi interaction. Experiments were corroborated by ab initio
      computations, which were performed using MP2 and M06-2X methods, with 6-311++G
      (d,p) and aug-cc-pVDZ basis sets. Single-point energy calculations were also done
      at MP2/CBS and CCSD(T)/CBS levels. The nature, strength, and origin of these
      noncovalent interactions were studied using AIM, NBO, and LMO-EDA analysis.

PMID- 29365255
TI  - Probing Anisotropic Surface Properties and Surface Forces of Fluorite Crystals.
AB  - Fluorite is the most important mineral source for producing fluorine-based
      chemicals and materials in a wide range of engineering and technological
      applications. In this work, atomic force microscopy was employed, for the first
      time, to probe the surface interactions and adhesion energy of model oleic acid
      (a commonly used surface modification organics for fluorite) molecules on
      fluorite surfaces with different orientations in both air and aqueous solutions
      at different pH conditions. Fitted with the Derjaguin-Landau-Verwey-Overbeek
      theory, the force results during surface approaching demonstrate the anisotropy
      in the surface charge of different orientations, with the {111} surface
      exhibiting a higher magnitude of surface charge, which could be attributed to the
      difference in the atomic composition. The adhesion measured during surface
      retraction shows that model oleic acid molecules have a stronger adhesion with
      the {100} surface than with the {111} surface in both air and aqueous solutions.
      The anisotropic adhesion energy was analyzed in relation to the surface atom
      (especially calcium) activity, which was supported by the surface free energy
      results calculated based on a three-probe-liquid method. Each calcium atom on the
      {100} surface with four dangling bonds is more active than the calcium atom on
      the {111} surface with only one dangling bond, supported by a larger value of the
      Lewis acid component for the {100} surface. The model oleic acid molecules
      present in the ionic form at pH 9 exhibit a higher adhesion energy with fluorite
      surfaces as compared to their molecular form at pH 6, which was related to the
      surface activity of different forms. The adhesion energy measured in solution is
      much lower than that in air, indicating that the solvent exerts an important
      influence on the interactions of organic molecules with mineral surfaces. The
      results provide useful information on the fundamental understanding of surface
      interactions and adhesion energy of organic molecules on mineral surfaces with
      different orientations, and the methodology can be extended to many other crystal
      surfaces in various interfacial processes.

PMID- 29365256
TI  - What is the Key for Accurate Absorption and Emission Calculations, Energy or
      Geometry?
AB  - Using a hierarchy of wave function methods, namely ADC(2), CC2, CCSD, CCSDR(3),
      and CC3, we investigate the absorption and emission energies in a set of 24
      organic compounds. For all molecules, reference values are determined at the
      CC3//CC3 or CCSDR(3)//CCSDR(3) levels and the energetic and geometric effects are
      decomposed considering all possible methodological combinations between the five
      considered methods. For absorption, it is found that the errors are mainly energy
      driven for ADC(2), CC2, and CCSDR(3), but not for CCSD. There is also an error
      compensation between the errors made on the geometries and transition energies
      for the two former approaches. For emission, the total errors are significantly
      larger than for absorption due to the significant increase of the structural
      component of the error. Therefore, the selection of a very refined method to
      compute the fluorescence energy will not systematically provide high accuracy if
      the excited-state geometry is not also optimized at a suitable level of theory.
      This is further demonstrated using results obtained from TD-DFT and hybrid TD
      DFT/wave function protocols. We also found that, compared to full CC3, only
      CCSDR(3) is able to deliver errors below the 0.1 eV threshold, a statement
      holding for both absorption (mean absolute error of 0.033 eV) and emission (mean
      absolute error of 0.066 eV).

PMID- 29365257
TI  - Scalable Super-Resolution Synthesis of Core-Vest Composites Assisted by Surface
      Plasmons.
AB  - The behavior of composite nanostructures depends on both size and elemental
      composition. Accordingly, concurrent control of size, shape, and composition of
      nanoparticles is key to tuning their functionality. In typical core-shell
      nanoparticles, the high degree of symmetry during shell formation results in
      fully encapsulated cores with severed access to the surroundings. We commingle
      light parameters (wavelength, intensity, and pulse duration) with the physical
      properties of nanoparticles (size, shape, and composition) to form hitherto
      unrealized core-vest composite nanostructures (CVNs). Unlike typical core-shells,
      the plasmonic core of the resulting CVNs selectively maintains physical access to
      its surrounding. Tunable variations in local temperature profiles ?50  degrees C
      are plasmonically induced over starburst-shaped nanoparticles as small as 50-100
      nm. These temperature variations result in CVNs where the shell coverage mirrors
      the temperature variations. The precision thus offered individually tailors
      access pathways of the core and the shell.

PMID- 29365258
TI  - Porphyrin-Loaded Pluronic Nanobubbles: A New US-Activated Agent for Future
      Theranostic Applications.
AB  - Sonodynamic therapy (SDT) has become a promising noninvasive approach for cancer
      therapy. The treatment exploits the ability of particular molecules (i.e.,
      porphyrins) to be excited by ultrasound and produce reactive oxygen species (ROS)
      during their decay process. These reactive species, in turn, result in cell
      death. To capitalize on the real-time visualization and on-demand delivery of
      ultrasound contrast agents, this study aims to combine porphyrins with
      nanobubbles (NBs) to obtain an ultrasound-activated theranostic agent that
      exploits the SDT activity in vitro. Two porphyrin classes, exposing different
      hydrophobic side chains, were synthesized. NB size and encapsulation efficiency
      were markedly dependent on the porphyrin structure. The combination of these
      porphyrin and NBs resulted in a significant reduction in cell viability upon
      sonication in pilot studies performed on the LS 174T colorectal cancer cell line.

PMID- 29365259
TI  - Light-Emitting Halide Perovskite Nanoantennas.
AB  - Nanoantennas made of high-index dielectrics with low losses in visible and
      infrared frequency ranges have emerged as a novel platform for advanced
      nanophotonic devices. On the other hand, halide perovskites are known to possess
      high refractive index, and they support excitons at room temperature with high
      binding energies and quantum yield of luminescence that makes them very
      attractive for all-dielectric resonant nanophotonics. Here we employ halide
      perovskites to create light-emitting nanoantennas with enhanced photoluminescence
      due to the coupling of their excitons to dipolar and multipolar Mie resonances.
      We demonstrate that the halide perovskite nanoantennas can emit light in the
      range of 530-770 nm depending on their composition. We employ a simple technique
      based on laser ablation of thin films prepared by wet-chemistry methods as a
      novel cost-effective approach for the fabrication of resonant perovskite
      nanostructures.

PMID- 29365260
TI  - Variable-Temperature NMR Spectroscopy, Conformational Analysis, and Thermodynamic
      Parameters of Cyclic Adenosine 5'-Diphosphate Ribose Agonists and Antagonists.
AB  - Cyclic adenosine 5'-diphosphate ribose (cADPR) is a ubiquitous Ca2+-releasing
      second messenger. Knowledge of its conformational landscape is an essential tool
      for unraveling the structure-activity relationship (SAR) in cADPR. Variable
      temperature 1H NMR spectroscopy, in conjunction with PSEUROT and population
      analyses, allowed us to determine the conformations and thermodynamic parameters
      of the furanose rings, gamma-bonds (C4'-C5'), and beta-bonds (C5'-O5') in the
      cADPR analogues 2'-deoxy-cADPR, 7-deaza-cADPR, and 8-bromo-cADPR. A significant
      finding was that, although the analogues are similar to each other and to cADPR
      itself in terms of overall conformation and population (DeltaG degrees ), there
      were subtle yet important differences in some of thermodynamic properties (DeltaH
      degrees , DeltaS degrees ) associated with each of the conformational equilibria.
      These differences prompted us to propose a model for cADPR in which the
      interactions between the A2'-N3, A5"-N3, and H2-R5' atoms serve to fine-tune the
      N-glycosidic torsion angles (chi).

PMID- 29365261
TI  - Proximity-Induced Superconductivity and Quantum Interference in Topological
      Crystalline Insulator SnTe Thin-Film Devices.
AB  - Topological crystalline insulators represent a new state of matter, in which the
      electronic transport is governed by mirror-symmetry protected Dirac surface
      states. Due to the helical spin-polarization of these surface states, the
      proximity of topological crystalline matter to a nearby superconductor is
      predicted to induce unconventional superconductivity and, thus, to host Majorana
      physics. We report on the preparation and characterization of Nb-based
      superconducting quantum interference devices patterned on top of topological
      crystalline insulator SnTe thin films. The SnTe films show weak anti
      localization, and the weak links of the superconducting quantum interference
      devices (SQUID) exhibit fully gapped proximity-induced superconductivity. Both
      properties give a coinciding coherence length of 120 nm. The SQUID oscillations
      induced by a magnetic field show 2pi periodicity, possibly dominated by the bulk
      conductivity.

PMID- 29365262
TI  - Dielectric Engineering of Electronic Correlations in a van der Waals
      Heterostructure.
AB  - Heterostructures of van der Waals bonded layered materials offer unique means to
      tailor dielectric screening with atomic-layer precision, opening a fertile field
      of fundamental research. The optical analyses used so far have relied on
      interband spectroscopy. Here we demonstrate how a capping layer of hexagonal
      boron nitride (hBN) renormalizes the internal structure of excitons in a WSe2
      monolayer using intraband transitions. Ultrabroadband terahertz probes
      sensitively map out the full complex-valued mid-infrared conductivity of the
      heterostructure after optical injection of 1s A excitons. This approach allows us
      to trace the energies and line widths of the atom-like 1s-2p transition of
      optically bright and dark excitons as well as the densities of these
      quasiparticles. The excitonic resonance red shifts and narrows in the WSe2/hBN
      heterostructure compared to the bare monolayer. Furthermore, the ultrafast
      temporal evolution of the mid-infrared response function evidences the formation
      of optically dark excitons from an initial bright population. Our results provide
      key insight into the effect of nonlocal screening on electron-hole correlations
      and open new possibilities of dielectric engineering of van der Waals
      heterostructures.

PMID- 29365263
TI  - Synthesizing 1T-1H Two-Phase Mo1-xWxS2 Monolayers by Chemical Vapor Deposition.
AB  - 1T-1H metal-semiconductor interfaces in two-dimensional (2D) transition-metal
      dichalcogenides (TMDs) play a crucial role in utilizing the band gaps of TMDs for
      applications in electronic devices. Although the 1T-1H two-phase structure has
      been observed in exfoliated 2D nanosheets and chemically or physically treated
      TMDs, it cannot in principle be achieved in large-scale TMD monolayers grown by
      chemical vapor deposition (CVD), which is a fabrication method for electronic
      device applications, because of the metastable nature of the 1T phase. In this
      study we report CVD growth of 1T-1H two phase TMD monolayers by controlling
      thermal strains and alloy compositions. It was found that in-plane thermal
      strains arising from the difference in thermal expansion coefficients between TMD
      monolayers and substrates can drive the 1H to 1T transition during cooling after
      CVD growth. Moreover, grain boundaries in the 2D crystals act as the nucleation
      sites of the 1T phase and the lattice strain perturbations from alloying
      noticeably promote the formation of the metastable 1T phase. This work has an
      important implication in tailoring structure and properties of CVD grown 2D TMDs
      by phase engineering.

PMID- 29365264
TI  - Deterministic Nanopatterning of Diamond Using Electron Beams.
AB  - Diamond is an ideal material for a broad range of current and emerging
      applications in tribology, quantum photonics, high-power electronics, and
      sensing. However, top-down processing is very challenging due to its extreme
      chemical and physical properties. Gas-mediated electron beam-induced etching
      (EBIE) has recently emerged as a minimally invasive, facile means to dry etch and
      pattern diamond at the nanoscale using oxidizing precursor gases such as O2 and
      H2O. Here we explain the roles of oxygen and hydrogen in the etch process and
      show that oxygen gives rise to rapid, isotropic etching, while the addition of
      hydrogen gives rise to anisotropic etching and the formation of topographic
      surface patterns. We identify the etch reaction pathways and show that the
      anisotropy is caused by preferential passivation of specific crystal planes. The
      anisotropy can be controlled by the partial pressure of hydrogen and by using a
      remote RF plasma source to radicalize the precursor gas. It can be used to
      manipulate the geometries of topographic surface patterns as well as nano- and
      microstructures fabricated by EBIE. Our findings constitute a comprehensive
      explanation of the anisotropic etch process and advance present understanding of
      electron-surface interactions.

PMID- 29365265
TI  - Solenoid Driven Pressure Valve System: Toward Versatile Fluidic Control in Paper
      Microfluidics.
AB  - As paper-based diagnostics has become predominantly driven by more advanced
      microfluidic technology, many of the research efforts are still focused on
      developing reliable and versatile fluidic control devices, apart from improving
      sensitivity and reproducibility. In this work, we introduce a novel and robust
      paper fluidic control system enabling versatile fluidic control. The system
      comprises a linear push-pull solenoid and an Arduino Uno microcontroller. The
      precisely controlled pressure exerted on the paper stops the flow. We first
      determined the stroke distance of the solenoid to obtain a constant pressure
      while examining the fluidic time delay as a function of the pressure. Results
      showed that strips of grade 1 chromatography paper had superior reproducibility
      in fluid transport. Next, we characterized the reproducibility of the fluidic
      velocity which depends on the type and grade of paper used. As such, we were able
      to control the flow velocity on the paper and also achieve a complete stop of
      flow with a pressure over 2.0 MPa. Notably, after the actuation of the pressure
      driven valve (PDV), the previously pressed area regained its original flow
      properties. This means that, even on a previously pressed area, multiple valve
      operations can be successfully conducted. To the best of our knowledge, this is
      the first demonstration of an active and repetitive valve operation in paper
      microfluidics. As a proof of concept, we have chosen to perform a multistep
      detection system in the form of an enzyme-linked immunosorbent assay with mouse
      IgG as the target analyte.

PMID- 29365267
TI  - Decoding the Three-Pronged Mechanism of NO3* Radical Formation in HNO3 Solutions
      at 22 and 80  degrees C Using Picosecond Pulse Radiolysis.
AB  - With nitric acid (HNO3) being at the core of nuclear technology through actinides
      separation and extraction processes, achieving a complete characterization of the
      complex processes involving concentrated HNO3 solutions under ionizing radiation
      equates bringing efficiency and safety into their operation. In this work, the
      three mechanisms contributing to the formation of nitrate radicals (NO3*) in
      concentrated nitric acid were investigated by measuring the radiolytic yield of
      NO3* in HNO3 solutions (0.5-23.5 M) at room (22.5  degrees C) and elevated (80 
      degrees C) temperatures on time scales spanning from picosecond to microsecond by
      pulse radiolysis measurements. We conclude that the formation yield of NO3*, just
      after the 7 ps electron pulse, is due to the direct effect and to the ultrafast
      electron transfer reaction between NO3- and the water cation radical, H2O*+. The
      absolute formation yield of NO3* radicals due to the direct effect, GNO3*dir, is
      found to be (3.4 +/- 0.1) * 10-7 mol.J-1, irrespective of the concentration and
      temperature. On longer time scales, >1 ns, an additional contribution to NO3*
      formation from the reaction between *OH radicals and undissociated HNO3 is
      observed. The rate constant of this reaction, which is activation-controlled, was
      determined to be (5.3 +/- 0.2) * 107 M-1.s-1 for 22.5  degrees C, reaching a
      value of (1.1 +/- 0.2) * 108 M-1.s-1 at 80  degrees C.

PMID- 29365266
TI  - Effect of Osmolytes on the Conformational Behavior of a Macromolecule in a
      Cytoplasm-like Crowded Environment: A Femtosecond Mid-IR Pump-Probe Spectroscopy
      Study.
AB  - Osmolytes found endogenously in almost all living beings play an important role
      in regulating cell volume under harsh environment. Here, to address the
      longstanding questions about the underlying mechanism of osmolyte effects, we use
      femtosecond mid-IR pump-probe spectroscopy with two different IR probes that are
      the OD stretching mode of HDO and the azido stretching mode of azido-derivatized
      poly(ethylene glycol) dimethyl ether (PEGDME). Our experimental results show that
      protecting osmolytes bind strongly with water molecules and dehydrate polymer
      surface, which results in promoting intramolecular interactions of the polymer.
      By contrast, urea behaves like water molecules without significantly disrupting
      water H-bonding network and favors extended and random-coil segments of the
      polymer chain by directly participating in solvation of the polymer. Our findings
      highlight the importance of direct interaction between urea and macromolecule,
      while protecting osmolytes indirectly affect the macromolecule through enhancing
      the water-osmolyte interaction in a crowded environment, which is the case that
      is often encountered in real biological systems.

PMID- 29365268
TI  - Monitoring Self-Assembly and Ligand Exchange of PbS Nanocrystal Superlattices at
      the Liquid/Air Interface in Real Time.
AB  - We investigate in situ the structural changes during self-assembly of PbS
      nanocrystals from colloidal solution into superlattices, solvent evaporation, and
      ligand exchange at the acetonitrile/air interface by grazing incidence small
      angle X-ray scattering (GISAXS). We simulate and fit the diffraction peaks under
      the distorted wave Born approximation (DWBA) to determine the lattice parameters.
      We observe a continuous isotropic contraction of the superlattice in two
      different assembly steps, preserving the body-centered cubic lattice with an
      overall decrease in the lattice constants of 11%. We argue that the first
      contraction period is due to a combination of solvent evaporation/annealing and
      capillary forces acting on the superlattice, whereas the second period is
      dominated by the effect of replacing oleic acid on the nanocrystal surface with
      the short and rigid cross-linker tetrathiafulvalene dicarboxylate. This work
      provides guidelines for optimized ligand exchange conditions and highlights the
      structural particularities arising from assembling NCs on liquid surfaces.

PMID- 29365269
TI  - Magneto-Spin-Orbit Graphene: Interplay between Exchange and Spin-Orbit Couplings.
AB  - A rich class of spintronics-relevant phenomena require implementation of robust
      magnetism and/or strong spin-orbit coupling (SOC) to graphene, but both
      properties are completely alien to it. Here, we for the first time experimentally
      demonstrate that a quasi-freestanding character, strong exchange splitting and
      giant SOC are perfectly achievable in graphene at once. Using angle- and spin
      resolved photoemission spectroscopy, we show that the Dirac state in the Au
      intercalated graphene on Co(0001) experiences giant splitting (up to 0.2 eV)
      while being by no means distorted due to interaction with the substrate. Our
      calculations, based on the density functional theory, reveal the splitting to
      stem from the combined action of the Co thin film in-plane exchange field and Au
      induced Rashba SOC. Scanning tunneling microscopy data suggest that the peculiar
      reconstruction of the Au/Co(0001) interface is responsible for the exchange field
      transfer to graphene. The realization of this "magneto-spin-orbit" version of
      graphene opens new frontiers for both applied and fundamental studies using its
      unusual electronic bandstructure.

PMID- 29365270
TI  - Creation and Annihilation of Charge Traps in Silicon Nanocrystals: Experimental
      Visualization and Spectroscopy.
AB  - Recent studies have shown the presence of an amorphous surface layer in nominally
      crystalline silicon nanocrystals (SiNCs) produced by some of the most common
      synthetic techniques. The amorphous surface layer can serve as a source of deep
      charge traps, which can dramatically affect the electronic and photophysical
      properties of SiNCs. We present results of a scanning tunneling
      microscopy/scanning tunneling spectroscopy (STM/STS) study of individual intragap
      states observed on the surfaces of hydrogen-passivated SiNCs deposited on the
      Au(111) surface. STS measurements show that intragap states can be formed
      reversibly when appropriate voltage-current pulses are applied to individual
      SiNCs. Analysis of STS spectra suggests that the observed intragap states are
      formed via self-trapping of charge carriers injected into SiNCs from the STM tip.
      Our results provide a direct visualization of the charge trap formation in
      individual SiNCs, a level of detail which until now had been achieved only in
      theoretical studies.

PMID- 29365272
TI  - Awake or Sedate . . . Do We Know the Best State?

PMID- 29365271
TI  - Full-Dimensional Quantum Dynamics of SiO in Collision with H2.
AB  - We report the first full-dimensional potential energy surface (PES) and quantum
      mechanical close-coupling calculations for scattering of SiO due to H2. The full
      dimensional interaction potential surface was computed using the explicitly
      correlated coupled-cluster (CCSD(T)-F12b) method and fitted using an invariant
      polynomial approach. Pure rotational quenching cross sections from initial states
      v1 = 0, j1 = 1-5 of SiO in collision with H2 are calculated for collision
      energies between 1.0 and 5000 cm-1. State-to-state rotational rate coefficients
      are calculated at temperatures between 5 and 1000 K. The rotational rate
      coefficients of SiO with para-H2 (p-H2) are compared with previous approximate
      results which were obtained using SiO-He PESs or scaled from SiO-He rate
      coefficients. Rovibrational state-to-state and total quenching cross sections and
      rate coefficients for initially excited SiO (v1 = 1, j1 = 0 and 1) in collisions
      with p-H2 (v2 = 0, j2 = 0) and ortho-H2 (o-H2) (v2 = 0, j2 = 1) are also
      obtained. The application of the current collisional rate coefficients to
      astrophysics is briefly discussed.

PMID- 29365274
TI  - 2-Methoxyestradiol causes matrix metalloproteinase 9-mediated transactivation of
      epidermal growth factor receptor and angiotensin type 1 receptor downregulation
      in rat aortic smooth muscle cells.
AB  - Studies have demonstrated the therapeutic potential of estrogen metabolite 2
      methoxyestradiol (2ME2) in several cardiovascular disorders, including
      hypertension. However, the exact mechanism(s) remains unknown. In this study,
      primary rat aortic smooth muscle cells (RASMCs) were exposed to 2ME2, and
      angiotensin type 1 receptor (AT1R) expression, function, and associated signaling
      pathways were evaluated. In RASMCs, 2ME2 downregulated AT1R expression in a
      concentration- and time-dependent manner, which was correlated with reduced mRNA
      expression. The 2ME2 effect was through G protein-coupled receptor 30 (GPR30)
      that inhibits second messenger cAMP. Moreover, 2ME2 exposure phosphorylated
      ERK1/2 that was sensitive to MEK inhibitor PD98059. Selective epidermal growth
      factor receptor (EGFR) inhibitor AG1478 blocked 2ME2-induced EGFR transactivation
      and attenuated subsequent phosphorylation of ERK1/2 preventing AT1R
      downregulation. The transactivation was dependent on 2ME2-induced release of
      matrix metalloproteinase 9 (MMP9) and epidermal growth factor demonstrated by
      ELISA. Furthermore, transfection with small interfering (si) RNA targeting MMP9
      impeded ERK1/2 activation and AT1R downregulation in response to 2ME2 and G1
      stimulation. Interestingly, under similar conditions, stimulation of GPR30 with
      the selective agonist G1 elicited similar signaling pathways and downregulated
      the AT1R expression that was reversed by GPR30 antagonist G15. Furthermore, 2ME2
      and G1 inhibited angiotensin II (ANG II) induced Ca2+ release, a response
      consistent with AT1R downregulation. Collectively, our study demonstrates for the
      first time that 2ME2 binding to GPR30 induces MMP9 specific transactivation of
      EGFR that mediates ERK1/2-dependent downregulation of AT1R in RASMCs. The study
      provides critical insights into the newly discovered role and signaling pathways
      of 2ME2 in the regulation of AT1R in vascular cells and its potential to be
      developed as a therapeutic agent that ameliorates hypertension.

PMID- 29365273
TI  - P2Y receptor regulation of K2P channels that facilitate K+ secretion by human
      mammary epithelial cells.
AB  - The objective of this study was to determine the molecular identity of ion
      channels involved in K+ secretion by the mammary epithelium and to examine their
      regulation by purinoceptor agonists. Apical membrane voltage-clamp experiments
      were performed on human mammary epithelial cells where the basolateral membrane
      was exposed to the pore-forming antibiotic amphotericin B dissolved in a solution
      with intracellular-like ionic composition. Addition of the Na+ channel inhibitor
      benzamil reduced the basal current, consistent with inhibition of Na+ uptake
      across the apical membrane, whereas the KCa3.1 channel blocker TRAM-34 produced
      an increase in current resulting from inhibition of basal K+ efflux. Treatment
      with two-pore potassium (K2P) channel blockers quinidine, bupivacaine and a
      selective TASK1/TASK3 inhibitor (PK-THPP) all produced concentration-dependent
      inhibition of apical K+ efflux. qRT-PCR experiments detected mRNA expression for
      nine K2P channel subtypes. Western blot analysis of biotinylated apical membranes
      and confocal immunocytochemistry revealed that at least five K2P subtypes (TWIK1,
      TREK1, TREK2, TASK1, and TASK3) are expressed in the apical membrane. Apical UTP
      also increased the current, but pretreatment with the PKC inhibitor GF109203X
      blocked the response. Similarly, direct activation of PKC with phorbol 12
      myristate 13-acetate produced a similar increase in current as observed with UTP.
      These results support the conclusion that the basal level of K+ secretion
      involves constitutive activity of apical KCa3.1 channels and multiple K2P channel
      subtypes. Apical UTP evoked a transient increase in KCa3.1 channel activity, but
      over time caused persistent inhibition of K2P channel function leading to an
      overall decrease in K+ secretion.

PMID- 29365275
TI  - Complementing Lung Cancer: How Tumor Cells Co-opt the Host Complement System to
      Reach Bone.

PMID- 29365276
TI  - Galectin-3 Promotes Vascular Remodeling and Contributes to Pulmonary
      Hypertension.

PMID- 29365277
TI  - IFN-beta Improves Sepsis-related Alveolar Macrophage Dysfunction and Postseptic
      Acute Respiratory Distress Syndrome-related Mortality.
AB  - IFN-beta is reported to improve survival in patients with acute respiratory
      distress syndrome (ARDS), possibly by preventing sepsis-induced
      immunosuppression, but its therapeutic nature in ARDS pathogenesis is poorly
      understood. We investigated the therapeutic effects of IFN-beta for postseptic
      ARDS to better understand its pathogenesis in mice. Postseptic ARDS was
      reproduced in mice by cecal ligation and puncture to induce sepsis, followed 4
      days later by intratracheal instillation of Pseudomonas aeruginosa to cause
      pneumonia with or without subcutaneous administration of IFN-beta 1 day earlier.
      Sepsis induced prolonged increases in alveolar TNF-alpha and IL-10 concentrations
      and innate immune reprogramming; specifically, it reduced alveolar macrophage
      (AM) phagocytosis and KC (CXCL1) secretion. Ex vivo AM exposure to TNF-alpha or
      IL-10 duplicated cytokine release impairment. Compared with sepsis or pneumonia
      alone, pneumonia after sepsis was associated with blunted alveolar KC responses
      and reduced neutrophil recruitment into alveoli despite increased neutrophil
      burden in lungs (i.e., "incomplete alveolar neutrophil recruitment"), reduced
      bacterial clearance, increased lung injury, and markedly increased mortality.
      Importantly, IFN-beta reversed the TNF-alpha/IL-10-mediated impairment of AM
      cytokine secretion in vitro, restored alveolar innate immune responsiveness in
      vivo, improved alveolar neutrophil recruitment and bacterial clearance, and
      consequently reduced the odds ratio for 7-day mortality by 85% (odds ratio, 0.15;
      95% confidence interval, 0.03-0.82; P = 0.045). This mouse model of sequential
      sepsis -> pneumonia infection revealed incomplete alveolar neutrophil recruitment
      as a novel pathogenic mechanism for postseptic ARDS, and systemic IFN-beta
      improved survival by restoring the impaired function of AMs, mainly by recruiting
      neutrophils to alveoli.

PMID- 29365278
TI  - CT imaging features of antiresorptive agent-related osteonecrosis of the
      jaw/medication-related osteonecrosis of the jaw.
AB  - OBJECTIVES: Antiresorptive agent-related osteonecrosis of the jaw
      (ARONJ)/medication-related osteonecrosis of the jaw (MRONJ) include both
      bisphosphonate-related osteonecrosis of jaw (BRONJ) and denosumab-related
      osteonecrosis of jaw (DRONJ). The purpose of this study is to study radiological
      characteristics of ARONJ/MRONJ. These imaging features may serve as one useful
      aid for assessing ARONJ/MRONJ. METHODS: CT scans of 74 Japanese patients, who
      were clinically diagnosed by inclusion criteria of ARONJ/MRONJ, obtained between
      April 1, 2011 and September 30, 2016, were evaluated. We investigated the CT
      imaging features of ARONJ/MRONJ, and clarified radiological differentiation
      between BRONJ and DRONJ, BRONJ due to oral bisphosphonate administration and due
      to intravenous bisphosphonate administration, BRONJ with respective kinds of
      medication, BRONJ with long-term administration and short-term administration,
      BRONJ with each clinical staging respectively. Fisher's exact test, chi2 test,
      Student's t-test and analysis of variance were performed in the statistical
      analyses. RESULTS: Unilateral maxillary sinusitis was detected in all patients
      with upper ARONJ/MRONJ (100%). DRONJ showed large sequestrum more frequently than
      BRONJ (3/4, 75 vs 3/35, 8.6%, p < 0.05). DRONJ showed periosteal reaction more
      frequently than BRONJ (4/10, 40 vs 7/65, 10.1%, p < 0.05). Patients of BRONJ
      resulting from intravenous bisphosphonate administration showed larger and more
      frequent buccolingual cortical bone perforations than BRONJ resulting from oral
      bisphosphonate administration (7/8, 87.5 vs 11/30, 36.7%, p < 0.05). There was no
      significant correlation between CT findings and respective kinds of medication,
      long/short-term administration, clinical stages of BRONJ. CONCLUSIONS:
      ARONJ/MRONJ has characteristic CT image findings which could be useful for its
      assessment.

PMID- 29365279
TI  - HIV gp120 in the Lungs of Antiretroviral Therapy-treated Individuals Impairs
      Alveolar Macrophage Responses to Pneumococci.
AB  - RATIONALE: People living with HIV are at significantly increased risk of invasive
      pneumococcal disease, despite long-term antiretroviral therapy (ART). The
      mechanism explaining this observation remains undefined. OBJECTIVES: To determine
      if apoptosis-associated microbicidal mechanisms, required to clear intracellular
      pneumococci that survive initial phagolysosomal killing, are perturbed. METHODS:
      Alveolar macrophages (AM) were obtained by BAL from healthy donors or HIV-1
      seropositive donors on long-term ART with undetectable plasma viral load.
      Monocyte-derived macrophages (MDM) were obtained from healthy donors and infected
      with HIV-1BaL or treated with gp120. Macrophages were challenged with opsonized
      serotype 2 Streptococcus pneumoniae and assessed for apoptosis, bactericidal
      activity, protein expression, and mitochondrial reactive oxygen species (mROS).
      AM phenotyping, ultrasensitive HIV-1 RNA quantification, and gp120 measurement
      were also performed in BAL. MEASUREMENTS AND MAIN RESULTS: HIV-1BaL infection
      impaired apoptosis, induction of mROS, and pneumococcal killing by MDM. Apoptosis
      associated pneumococcal killing was also reduced in AM from ART-treated HIV-1
      seropositive donors. BAL fluid from these individuals demonstrated persistent
      lung CD8+ T lymphocytosis, and gp120 or HIV-1 RNA was also detected. Despite
      this, transcriptional activity in AM freshly isolated from people living with HIV
      was broadly similar to healthy volunteers. Instead, gp120 phenocopied the defect
      in pneumococcal killing in healthy MDM through post-translational modification of
      Mcl-1, preventing apoptosis induction, caspase activation, and increased mROS
      generation. Moreover, gp120 also inhibited mROS-dependent pneumococcal killing in
      MDM. CONCLUSIONS: Despite ART, HIV-1, via gp120, drives persisting innate immune
      defects in AM microbicidal mechanisms, enhancing susceptibility to pneumococcal
      disease.

PMID- 29365280
TI  - Microparticulate Caspase 1 Regulates Gasdermin D and Pulmonary Vascular
      Endothelial Cell Injury.
AB  - Lung endothelial cell apoptosis and injury occur throughout all stages of acute
      lung injury/acute respiratory distress syndrome and impact disease progression.
      Caspases 1, 4, and 5 are essential for completion of the apoptotic program known
      as pyroptosis that also involves proinflammatory cytokines. Because gasdermin D
      (GSDMD) mediates pyroptotic death and is essential for pore formation, we
      hypothesized that it might direct caspase 1-encapsulated microparticle (MP)
      release and mediate endothelial cell death. Our present work provides evidence
      that GSDMD is released by LPS-stimulated THP-1 monocytic cells, where it is
      packaged into microparticles together with active caspase 1. Furthermore, only MP
      released from stimulated monocytic cells that contain both cleaved GSDMD and
      active caspase 1 induce endothelial cell apoptosis. MPs pretreated with caspase 1
      inhibitor Y-VAD or pan-caspase inhibitor Z-VAD do not contain cleaved GSDMD. MPs
      from caspase 1-knockout cells are also deficient in p30 active GSDMD, further
      confirming that caspase 1 regulates GSDMD function. Although control MPs
      contained cleaved GSDMD without caspase 1, these fractions were unable to induce
      cell death, suggesting that encapsulation of both caspase 1 and GSDMD is
      essential for cell death induction. Release of microparticulate active caspase 1
      was abrogated in GSDMD knockout cells, although cytosolic caspase 1 activation
      was not impaired. Last, higher concentrations of microparticulate GSDMD were
      detected in the plasma of septic patients with acute respiratory distress
      syndrome than in that of healthy donors. Taken together, these findings suggest
      that GSDMD regulates the release of microparticulate active caspase 1 from
      monocytes essential for induction of cell death and thereby may play a critical
      role in sepsis-induced endothelial cell injury.

PMID- 29365281
TI  - Moving Ahead with a New NEJM.org.

PMID- 29365283
TI  - Discounted Drugs for Needy Patients and Hospitals - Understanding the 340B
      Debate.

PMID- 29365282
TI  - Consequences of the 340B Drug Pricing Program.
AB  - BACKGROUND: The 340B Drug Pricing Program entitles qualifying hospitals to
      discounts on outpatient drugs, increasing the profitability of drug
      administration. By tying the program eligibility of hospitals to their
      Disproportionate Share Hospital (DSH) adjustment percentage, which reflects the
      proportion of hospitalized patients who are low-income, the program is intended
      to expand resources for underserved populations but provides no direct incentives
      for hospitals to use financial gains to enhance care for low-income patients.
      METHODS: We used Medicare claims and a regression-discontinuity design, taking
      advantage of the threshold for program eligibility among general acute care
      hospitals (DSH percentage, >11.75%), to isolate the effects of the program on
      hospital-physician consolidation (i.e., acquisition of physician practices or
      employment of physicians by hospitals) and on the outpatient administration of
      parenteral drugs by hospital-owned facilities in three specialties in which
      parenteral drugs are frequently used. For low-income patients, we also assessed
      the effects of the program on the provision of care by hospitals and on
      mortality. RESULTS: Hospital eligibility for the 340B Program was associated with
      2.3 more hematologist-oncologists practicing in facilities owned by the hospital,
      or 230% more hematologist-oncologists than expected in the absence of the program
      (P=0.02), and with 0.9 (or 900%) more ophthalmologists per hospital (P=0.08) and
      0.1 (or 33%) more rheumatologists per hospital (P=0.84). Program eligibility was
      associated with significantly higher numbers of parenteral drug claims billed by
      hospitals for Medicare patients in hematology-oncology (90% higher, P=0.001) and
      ophthalmology (177% higher, P=0.03) but not rheumatology (77% higher, P=0.12).
      Program eligibility was associated with lower proportions of low-income patients
      in hematology-oncology and ophthalmology and with no significant differences in
      hospital provision of safety-net or inpatient care for low-income groups or in
      mortality among low-income residents of the hospitals' local service areas.
      CONCLUSIONS: The 340B Program has been associated with hospital-physician
      consolidation in hematology-oncology and with more hospital-based administration
      of parenteral drugs in hematology-oncology and ophthalmology. Financial gains for
      hospitals have not been associated with clear evidence of expanded care or lower
      mortality among low-income patients. (Funded by the Agency for Healthcare
      Research and Quality and others.).

PMID- 29365285
TI  - Ectopic expression of Miro 1 ameliorates seizures and inhibits hippocampal
      neurodegeneration in a mouse model of pilocarpine epilepsy.
AB  - Epilepsy is a common disease of the central nervous system. This study aimed to
      investigate the role of mitochondrial Rho (Miro) 1 in epilepsy, using a mouse
      model of pilocarpine-induced status epilepticus (SE). Intraperitoneal injection
      of pilocarpine induced epileptic seizures in mice and significantly decreased
      Miro 1 expression in the hippocampus. Moreover, pilocarpine treatment increased
      the serum levels of heat shock protein 70 (HSP70) and S100 calcium binding
      protein B (S100B) and led to hippocampal neuronal injury and apoptosis. The
      intrinsic apoptotic pathway was activated in the hippocampal neurons following
      pilocarpine-induced SE, as evidenced by increased levels of cleaved caspase-3 and
      Bax, downregulation of Bcl-2, and the release of cytochrome c from mitochondria
      to cytoplasm. By contrast, forced expression of Miro 1 by lateral ventricular
      administration of adenovirus mitigated pilocarpine-induced epileptic seizures,
      reduced the elevation of HSP70 and S100B, and inhibited hippocampal neuronal
      apoptosis by suppressing the intrinsic apoptotic pathway. In summary, our data
      demonstrates that ectopic expression of Miro 1 alleviated pilocarpine-induced SE
      and protected hippocampal neurons by inhibiting the intrinsic apoptotic pathway.
      These findings provide new insights into epileptic disorders and suggest a
      potential neuroprotective value of Miro 1 in the treatment of epilepsy.

PMID- 29365286
TI  - Effect of cluster set warm-up configurations on sprint performance in collegiate
      male soccer players.
AB  - The purpose of this study was to determine if back squat cluster sets (CS) with
      varying inter-repetition rest periods would potentiate greater sprint performance
      compared with a traditional set parallel back squat in collegiate soccer players.
      Twelve collegiate male soccer players (age, 21.0 +/- 2.0 years; height, 180.0 +/-
      9.0 cm; body mass, 79.0 +/- 9.5 kg) performed a 20-m sprint prior to a
      potentiation complex and at 1, 4, 7, and 10 min postexercise on 3 separate,
      randomized occasions. On each occasion, the potentiation complex consisted of 1
      set of 3 repetitions at 85% 1-repetition maximum (1RM) for the traditional
      parallel back squat. However, on 1 occasion the 3-repetition set was performed in
      a traditional manner (i.e., continuously), whereas on the other 2 occasions, 30s
      (CS30) and 60 s (CS60) of rest were allotted between each repetition. Repeated
      measures ANOVA revealed greater (p = 0.022) mean barbell velocity on CS60
      compared with the traditional set. However, faster (p < 0.040) 20-m sprint times
      were observed for CS30 (3.15 +/- 0.16 s) compared with traditional (3.20 +/- 0.17
      s) only at 10 min postexercise. No other differences were observed. These data
      suggest that a single cluster set of 3 repetitions with 30-s inter-repetition
      rest periods at 85% 1RM acutely improves 20-m sprinting performance. Strength and
      conditioning professionals and their athletes might consider its inclusion during
      the specific warm-up to acutely improve athletic performance during the onset
      (<=10 min) of training or competition.

PMID- 29365284
TI  - Obesity, body weight regulation and the brain: insights from fMRI.
AB  - Obesity constitutes a major global health threat. Despite the success of
      bariatric surgery in delivering sustainable weight loss and improvement in
      obesity-related morbidity, effective non-surgical treatments are urgently needed,
      necessitating an increased understanding of body weight regulation. Neuroimaging
      studies undertaken in people with healthy weight, overweight, obesity and
      following bariatric surgery have contributed to identifying the
      neurophysiological changes seen in obesity and help increase our understanding of
      the mechanisms driving the favourable eating behaviour changes and sustained
      weight loss engendered by bariatric surgery. These studies have revealed a key
      interplay between peripheral metabolic signals, homeostatic and hedonic brain
      regions and genetics. Findings from brain functional magnetic resonance imaging
      (fMRI) studies have consistently associated obesity with an increased
      motivational drive to eat, increased reward responses to food cues and impaired
      food-related self-control processes. Interestingly, new data link these obesity
      associated changes with structural and connectivity changes within the central
      nervous system. Moreover, emerging data suggest that bariatric surgery leads to
      neuroplastic recovery. A greater understanding of the interactions between
      peripheral signals of energy balance, the neural substrates that regulate eating
      behaviour, the environment and genetics will be key for the development of novel
      therapeutic strategies for obesity. This review provides an overview of our
      current understanding of the pathoaetiology of obesity with a focus upon the role
      that fMRI studies have played in enhancing our understanding of the central
      regulation of eating behaviour and energy homeostasis.

PMID- 29365287
TI  - Platelets Play a Central Role in Sensitization to Allergen.
AB  - Platelet activation occurs in patients with allergic inflammation, and platelets
      can be activated directly by allergen via an IgE-dependent process. Platelets
      have been shown to activate APCs such as CD11c+ dendritic cells in vitro.
      Although CD11c+ dendritic cells are a requisite for allergen sensitization, the
      role of platelets in this process is unknown. In this study, we investigated
      whether platelets were necessary for allergen sensitization. Balb/c mice
      sensitized to ovalbumin were exposed to subsequent aerosolized allergen
      (ovalbumin challenge). We analyzed lung CD11c+ cell activation, colocalization
      with platelets, and some other indices of inflammation. The role of platelets at
      the time of allergen sensitization was assessed through platelet depletion
      experiments restricted to the period of sensitization. Platelets colocalized with
      airway CD11c+ cells, and this association increased after allergen sensitization
      as well as after subsequent allergen exposure. Temporary platelet depletion
      (>95%) at the time of allergen sensitization led to a suppression of IgE and IL-4
      synthesis and to a decrease in the pulmonary recruitment of eosinophils,
      macrophages, and lymphocytes after subsequent allergen exposure. Furthermore, in
      mice previously depleted of platelets at the time of sensitization, the recovered
      platelet population was shown to have reduced expression of FcepsilonRI.
      Pulmonary CD11c+ cell recruitment was suppressed in these mice after allergen
      challenge, suggesting that the migration of CD11c+ cells in vivo may be dependent
      on direct platelet recognition of allergen. We conclude that platelets are
      necessary for efficient host sensitization to allergen. This propagates the
      subsequent inflammatory response during secondary allergen exposure and increases
      platelet association with airway CD11c+ cells.

PMID- 29365288
TI  - Influences of Cesarean Delivery on Breastfeeding Practices and Duration: A
      Prospective Cohort Study.
AB  - BACKGROUND: Mothers are encouraged to exclusively breastfeed for the first 6
      months. However, cesarean delivery rates have increased worldwide, which may
      affect breastfeeding. Research aim: This study aimed to determine the potential
      effects of cesarean delivery on breastfeeding practices and breastfeeding
      duration. METHODS: This was a 6-month cohort study extracted from a 24-month
      prospective cohort study of mother-infant pairs in three communities in Hunan,
      China. Data about participants' characteristics, delivery methods, breastfeeding
      initiation, use of formula in the hospital, exclusive breastfeeding, and any
      breastfeeding were collected at 1, 3, and 6 months following each infant's birth.
      The chi-square test, logistic regression model, and Cox proportional hazard
      regression model were used to examine the relationship between breastfeeding
      practices and cesarean delivery. RESULTS: The number of women who had a cesarean
      delivery was 387 (40.6%), and 567 (59.4%) women had a vaginal delivery. The
      exclusive breastfeeding rates at 1, 3, and 6 months were 80.2%, 67.4%, and 21.5%,
      respectively. Women who had a cesarean delivery showed a lower rate of exclusive
      breastfeeding and any breastfeeding than those who had a vaginal delivery ( p <
      .05). In addition, cesarean delivery was related with using formula in the
      hospital and delayed breastfeeding initiation. Cesarean delivery also shortened
      the breastfeeding duration (hazard ratio = 1.40, 95% confidence interval [1.06,
      1.84]). CONCLUSION: Healthcare professionals should provide more breastfeeding
      skills to women who have a cesarean delivery and warn mothers about the dangers
      of elective cesarean section for breastfeeding practices.

PMID- 29365289
TI  - Comparative genome analysis to identify SNPs associated with high oleic acid and
      elevated protein content in soybean.
AB  - The objective of this study was to determine the genetic relationship between the
      oleic acid and protein content. The genotypes having high oleic acid and elevated
      protein (HOEP) content were crossed with five elite lines having normal oleic
      acid and average protein (NOAP) content. The selected accessions were grown at
      six environments in three different locations and phenotyped for protein, oil,
      and fatty acid components. The mean protein content of parents, HOEP, and NOAP
      lines was 34.6%, 38%, and 34.9%, respectively. The oleic acid concentration of
      parents, HOEP, and NOAP lines was 21.7%, 80.5%, and 20.8%, respectively. The HOEP
      plants carried both FAD2-1A (S117N) and FAD2-1B (P137R) mutant alleles
      contributing to the high oleic acid phenotype. Comparative genome analysis using
      whole-genome resequencing data identified six genes having single nucleotide
      polymorphism (SNP) significantly associated with the traits analyzed. A single
      SNP in the putative gene Glyma.10G275800 was associated with the elevated protein
      content, and palmitic, oleic, and linoleic acids. The genes from the marker
      intervals of previously identified QTL did not carry SNPs associated with protein
      content and fatty acid composition in the lines used in this study, indicating
      that all the genes except Glyma.10G278000 may be the new genes associated with
      the respective traits.

PMID- 29365291
TI  - A comparative study on the effects of high-fat diet and endurance training on the
      PGC-1alpha-FNDC5/irisin pathway in obese and nonobese male C57BL/6 mice.
AB  - The present study was performed to clarify how a combined exercise/diet treatment
      could affect the expression level of the muscle fibronectin type III domain
      containing 5 (Fndc5) with respect to body fat mass. Male C57BL/6 mice were
      divided into 2 groups including low-fat (LF) and high-fat (HF) diets for 12
      weeks. Then, LF fed (nonobese) and HF fed mice (obese) were divided into the
      following 4 groups: HF-Exercise, HF-Sedentary, LF-Exercise, and LF-Sedentary. The
      exercise group exercised on a motor-driven treadmill for 45 min/day, 5 days/week
      for 8 weeks. Mice were sacrificed 24 h after the final exercise session.
      Gastrocnemius muscle and the visceral adipose tissue were excised and frozen for
      the assessment of proliferator-activated receptor gamma coactivator 1 alpha (Pgc
      1alpha) and Fndc5 messenger RNA (mRNA) and protein levels. Data indicated that
      protein level of muscle PGC-1alpha was decreased in HF versus LF groups and in
      obese versus nonobese mice. Moreover, Fndc5 mRNA levels were increased in the
      muscle tissue of HF versus LF groups and in obese versus nonobese mice. Also, in
      the gastrocnemius skeletal muscle, protein levels of FNDC5 were significantly
      higher in the HF fed mice, as compared with their low-fat fed counterparts,
      similar to what was observed for exercised versus sedentary mice. Overall, we
      found that the HF diet increased Fndc5 transcript levels in the skeletal muscle,
      but exercise had a minimal effect on the transcript level of Fndc5, whereas
      endurance training increased the protein content of FNDC5 in the skeletal muscle.

PMID- 29365290
TI  - Gray scale and doppler ultrasonography features of the carcinoma ex pleomorphic
      adenoma.
AB  - OBJECTIVES: For lesions in the salivary glands, ultrasonography (US) is an ideal
      tool for initial assessment. The aim of this study was to characterize and
      differentiate between the Gray scale and Doppler US findings of intracapsular
      carcinoma ex pleomorphic adenoma (Ic-CxPA) and invasive carcinoma ex pleomorphic
      adenoma (Inv-CxPA). METHODS: A total of 87 patients (89 lesions) with
      histopathologically proven CxPA underwent US examination. The following
      characteristics were assessed on US images: size, shape, border, echogenicity,
      echo texture, posterior echo, vascularity, and regional lymph node enlargement.
      One-way analysis of variance (ANOVA), nonparametric test, Fisher's exact test,
      chi-square test and receiver operating characteristic (ROC) curve were used for
      the analyses of the US findings of Ic-CxPAs and Inv-CxPAs. RESULTS: We found that
      on US images, nearly all Ic-CxPAs (10/11) and a few of Inv-CxPAs (17/78) showed
      benign features, such as a regular shape, a well-defined border, and enhancement
      of posterior echo, while most Inv-CxPAs (61/78) showed one or more following
      features: an irregular shape, an ill-defined border, and lack of enhancement of
      posterior echo. CONCLUSIONS: Ic-CxPAs tended to exhibit benign features, whereas
      most Inv-CxPAs tended to exhibit one or more invasive features. US can provide
      strong evidence in differentiating Inv-CxPAs from Ic-CxPAs.

PMID- 29365292
TI  - 3D cinematic rendering of the calvarium, maxillofacial structures, and skull
      base: preliminary observations.
AB  - Three-dimensional (3D) visualizations of volumetric data from CT have gained
      widespread clinical acceptance and are an important method for evaluating complex
      anatomy and pathology. Recently, cinematic rendering (CR), a new 3D visualization
      methodology, has become available. CR utilizes a lighting model that allows for
      the production of photorealistic images from isotropic voxel data. Given how new
      this technique is, studies to evaluate its clinical utility and any potential
      advantages or disadvantages relative to other 3D methods such as volume rendering
      have yet to be published. In this pictorial review, we provide examples of normal
      calvarial, maxillofacial, and skull base anatomy and pathological conditions that
      highlight the potential for CR images to aid in patient evaluation and treatment
      planning. The highly detailed images and nuanced shadowing that are intrinsic to
      CR are well suited to the display of the complex anatomy in this region of the
      body. We look forward to studies with CR that will ascertain the ultimate value
      of this methodology to evaluate calvarium, maxillofacial, and skull base
      morphology as well as other complex anatomic structures.

PMID- 29365293
TI  - Telehealth.

PMID- 29365295
TI  - Amyloid-Beta Solubility in the Treatment of Alzheimer's Disease.

PMID- 29365294
TI  - Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease.
AB  - BACKGROUND: Alzheimer's disease is characterized by amyloid-beta (Abeta) plaques
      and neurofibrillary tangles. The humanized monoclonal antibody solanezumab was
      designed to increase the clearance from the brain of soluble Abeta, peptides that
      may lead to toxic effects in the synapses and precede the deposition of
      fibrillary amyloid. METHODS: We conducted a double-blind, placebo-controlled,
      phase 3 trial involving patients with mild dementia due to Alzheimer's disease,
      defined as a Mini-Mental State Examination (MMSE) score of 20 to 26 (on a scale
      from 0 to 30, with higher scores indicating better cognition) and with amyloid
      deposition shown by means of florbetapir positron-emission tomography or Abeta1
      42 measurements in cerebrospinal fluid. Patients were randomly assigned to
      receive solanezumab at a dose of 400 mg or placebo intravenously every 4 weeks
      for 76 weeks. The primary outcome was the change from baseline to week 80 in the
      score on the 14-item cognitive subscale of the Alzheimer's Disease Assessment
      Scale (ADAS-cog14; scores range from 0 to 90, with higher scores indicating
      greater cognitive impairment). RESULTS: A total of 2129 patients were enrolled,
      of whom 1057 were assigned to receive solanezumab and 1072 to receive placebo.
      The mean change from baseline in the ADAS-cog14 score was 6.65 in the solanezumab
      group and 7.44 in the placebo group, with no significant between-group difference
      at week 80 (difference, -0.80; 95% confidence interval, -1.73 to 0.14; P=0.10).
      As a result of the failure to reach significance with regard to the primary
      outcome in the prespecified hierarchical analysis, the secondary outcomes were
      considered to be descriptive and are reported without significance testing. The
      change from baseline in the MMSE score was -3.17 in the solanezumab group and 
      3.66 in the placebo group. Adverse cerebral edema or effusion lesions that were
      observed on magnetic resonance imaging after randomization occurred in 1 patient
      in the solanezumab group and in 2 in the placebo group. CONCLUSIONS: Solanezumab
      at a dose of 400 mg administered every 4 weeks in patients with mild Alzheimer's
      disease did not significantly affect cognitive decline. (Funded by Eli Lilly;
      EXPEDITION3 ClinicalTrials.gov number, NCT01900665 .).

PMID- 29365296
TI  - To Care Is Human - Collectively Confronting the Clinician-Burnout Crisis.

PMID- 29365297
TI  - Fertility Preservation in Women.

PMID- 29365298
TI  - PEPFAR - 15 Years and Counting the Lives Saved.

PMID- 29365299
TI  - Surgery for Drug-Resistant Epilepsy in Children.

PMID- 29365300
TI  - Calcified Spleen and Gallstones.

PMID- 29365301
TI  - Beyond Burnout - Redesigning Care to Restore Meaning and Sanity for Physicians.

PMID- 29365302
TI  - Rivaroxaban in Stable Cardiovascular Disease.

PMID- 29365303
TI  - Hemorrhagic Shock.

PMID- 29365304
TI  - Creutzfeldt-Jakob Disease.

PMID- 29365305
TI  - Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection.
AB  - BACKGROUND: Acute myocardial infarction can be triggered by acute respiratory
      infections. Previous studies have suggested an association between influenza and
      acute myocardial infarction, but those studies used nonspecific measures of
      influenza infection or study designs that were susceptible to bias. We evaluated
      the association between laboratory-confirmed influenza infection and acute
      myocardial infarction. METHODS: We used the self-controlled case-series design to
      evaluate the association between laboratory-confirmed influenza infection and
      hospitalization for acute myocardial infarction. We used various high-specificity
      laboratory methods to confirm influenza infection in respiratory specimens, and
      we ascertained hospitalization for acute myocardial infarction from
      administrative data. We defined the "risk interval" as the first 7 days after
      respiratory specimen collection and the "control interval" as 1 year before and 1
      year after the risk interval. RESULTS: We identified 364 hospitalizations for
      acute myocardial infarction that occurred within 1 year before and 1 year after a
      positive test result for influenza. Of these, 20 (20.0 admissions per week)
      occurred during the risk interval and 344 (3.3 admissions per week) occurred
      during the control interval. The incidence ratio of an admission for acute
      myocardial infarction during the risk interval as compared with the control
      interval was 6.05 (95% confidence interval [CI], 3.86 to 9.50). No increased
      incidence was observed after day 7. Incidence ratios for acute myocardial
      infarction within 7 days after detection of influenza B, influenza A, respiratory
      syncytial virus, and other viruses were 10.11 (95% CI, 4.37 to 23.38), 5.17 (95%
      CI, 3.02 to 8.84), 3.51 (95% CI, 1.11 to 11.12), and 2.77 (95% CI, 1.23 to 6.24),
      respectively. CONCLUSIONS: We found a significant association between respiratory
      infections, especially influenza, and acute myocardial infarction. (Funded by the
      Canadian Institutes of Health Research and others.).

PMID- 29365306
TI  - Treating and Preventing HIV with Generic Drugs - Barriers in the United States.

PMID- 29365307
TI  - Monitoring Neuromuscular Function.

PMID- 29365308
TI  - Case 3-2018: A 5-Month-Old Boy with Hypoglycemia.

PMID- 29365310
TI  - Aquaporin 11 is related to cryotolerance and fertilising ability of frozen?thawed
      bull spermatozoa.
AB  - Aquaporins (AQPs) are channel proteins involved in the transport of water and
      solutes across biological membranes. In the present study we identified and
      localised aquaporin 11 (AQP11) in bull spermatozoa and investigated the
      relationship between the relative AQP11 content, sperm cryotolerance and the
      fertilising ability of frozen-thawed semen. Bull ejaculates were classified into
      two groups of good and poor freezability and assessed through immunofluorescence
      and immunoblotting analyses before and after cryopreservation. AQP11 was
      localised throughout the entire tail and along the sperm head. These findings
      were confirmed through immunoblotting, which showed a specific band of
      approximately 50 kDa corresponding to AQP11. The relative amount of AQP11 was
      significantly (P<0.05) higher in both fresh and frozen-thawed spermatozoa from
      bull ejaculates with good freezability compared with those with poorer
      freezability. In addition, in vitro oocyte penetration rates and non-return rates
      56 days after AI were correlated with the relative AQP11 content in fresh
      spermatozoa. In conclusion, AQP11 is present in the head and tail of bull
      spermatozoa and its relative amount in fresh and frozen-thawed spermatozoa is
      related to the resilience of the spermatozoa to withstand cryopreservation and
      the fertilising ability of frozen-thawed spermatozoa. Further research is needed
      to elucidate the actual role of sperm AQP11 in bovine fertility.

PMID- 29365309
TI  - Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection.
AB  - BACKGROUND: Glecaprevir and pibrentasvir are direct-acting antiviral agents with
      pangenotypic activity and a high barrier to resistance. We evaluated the efficacy
      and safety of 8-week and 12-week courses of treatment with 300 mg of glecaprevir
      plus 120 mg of pibrentasvir in patients without cirrhosis who had hepatitis C
      virus (HCV) genotype 1 or 3 infection. METHODS: We conducted two phase 3,
      randomized, open-label, multicenter trials. Patients with genotype 1 infection
      were randomly assigned in a 1:1 ratio to receive once-daily glecaprevir
      pibrentasvir for either 8 or 12 weeks. Patients with genotype 3 infection were
      randomly assigned in a 2:1 ratio to receive 12 weeks of treatment with either
      glecaprevir-pibrentasvir or sofosbuvir-daclatasvir. Additional patients with
      genotype 3 infection were subsequently enrolled and nonrandomly assigned to
      receive 8 weeks of treatment with glecaprevir-pibrentasvir. The primary end point
      was the rate of sustained virologic response 12 weeks after the end of treatment.
      RESULTS: In total, 1208 patients were treated. The rate of sustained virologic
      response at 12 weeks among genotype 1-infected patients was 99.1% (95% confidence
      interval [CI], 98 to 100) in the 8-week group and 99.7% (95% CI, 99 to 100) in
      the 12-week group. Genotype 3-infected patients who were treated for 12 weeks had
      a rate of sustained virologic response at 12 weeks of 95% (95% CI, 93 to 98; 222
      of 233 patients) with glecaprevir-pibrentasvir and 97% (95% CI, 93 to 99.9; 111
      of 115) with sofosbuvir-daclatasvir; 8 weeks of treatment with glecaprevir
      pibrentasvir yielded a rate of 95% (95% CI, 91 to 98; 149 of 157 patients).
      Adverse events led to discontinuation of treatment in no more than 1% of patients
      in any treatment group. CONCLUSIONS: Once-daily treatment with glecaprevir
      pibrentasvir for either 8 weeks or 12 weeks achieved high rates of sustained
      virologic response among patients with HCV genotype 1 or 3 infection who did not
      have cirrhosis. (Funded by AbbVie; ENDURANCE-1 and ENDURANCE-3 ClinicalTrials.gov
      numbers, NCT02604017 and NCT02640157 .).

PMID- 29365311
TI  - Biocompatible coupling of therapeutic fusion proteins to human erythrocytes.
AB  - Carriage of drugs by red blood cells (RBCs) modulates pharmacokinetics,
      pharmacodynamics, and immunogenicity. However, optimal targets for attaching
      therapeutics to human RBCs and adverse effects have not been studied. We
      engineered nonhuman-primate single-chain antibody fragments (scFvs) directed to
      human RBCs and fused scFvs with human thrombomodulin (hTM) as a representative
      biotherapeutic cargo (hTM-scFv). Binding fusions to RBCs on band 3/glycophorin A
      (GPA; Wright b [Wrb] epitope) and RhCE (Rh17/Hr0 epitope) similarly endowed RBCs
      with hTM activity, but differed in their effects on RBC physiology. scFv and hTM
      scFv targeted to band 3/GPA increased membrane rigidity and sensitized RBCs to
      hemolysis induced by mechanical stress, while reducing sensitivity to hypo
      osmotic hemolysis. Similar properties were seen for other ligands bound to GPA
      and band 3 on human and murine RBCs. In contrast, binding of scFv or hTM-scFv to
      RhCE did not alter deformability or sensitivity to mechanical and osmotic stress
      at similar copy numbers bound per RBCs. Contrasting responses were also seen for
      immunoglobulin G antibodies against band 3, GPA, and RhCE. RBC-bound hTM-scFv
      generated activated protein C (APC) in the presence of thrombin, but RhCE
      targeted hTM-scFv demonstrated greater APC generation per bound copy. Both Wrb-
      and RhCE-targeted fusion proteins inhibited fibrin deposition induced by tumor
      necrosis factor-alpha in an endothelialized microfluidic model using human whole
      blood. RhCE-bound hTM-scFv more effectively reduced platelet and leukocyte
      adhesion, whereas anti-Wrb scFv appeared to promote platelet adhesion. These data
      provide a translational framework for the development of engineered affinity
      ligands to safely couple therapeutics to human RBCs.

PMID- 29365313
TI  - The human IL-15 superagonist ALT-803 directs SIV-specific CD8+ T cells into B
      cell follicles.
AB  - Sequestering of latent HIV in follicular helper T cells within B-cell follicles
      that largely exclude cytotoxic T cells is a major barrier to cellular immune
      based approaches to eradicate HIV. Here, we show that the clinical-grade human
      interleukin-15 (IL-15) superagonist ALT-803 activates and redirects simian
      immunodeficiency virus (SIV)-specific CD8+ T cells from the peripheral blood into
      B-cell follicles. In agreement with the increased trafficking of SIV-specific
      cytotoxic T cells to sites of cryptic viral replication, lymph nodes of elite
      controlling macaques contained fewer cells expressing SIV RNA or harboring SIV
      DNA post-ALT-803 treatment. These data establish ALT-803 as an immunotherapeutic
      for HIV and other chronic viral pathogens that evade host immunity by persisting
      in B-cell follicles.

PMID- 29365315
TI  - Kwun J, Burghuber C, Manook M, et al. Successful desensitization with proteasome
      inhibition and costimulation blockade in sensitized nonhuman primates. Blood Adv.
      2017;1(24):2115-2119.

PMID- 29365312
TI  - Mutational dynamics of early and late relapsed childhood ALL: rapid clonal
      expansion and long-term dormancy.
AB  - Childhood acute lymphoblastic leukemia (cALL) is the most frequent pediatric
      cancer. Refractory/relapsed cALL presents a survival rate of ~45% and is still
      one of the leading causes of death by disease among children. Mechanisms, such as
      clonal competition and evolutionary adaptation, govern treatment resistance.
      However, the underlying clonal dynamics leading to multiple relapses and
      differentiating early (<36 months postdiagnosis) from late relapse events remain
      elusive. Here, we use an integrative genome-based analysis combined with serial
      sampling of relapsed tumors (from primary tumor to <=4 relapse events) from 19
      pre-B-cell cALL patients (8 early and 11 late relapses) to assess the fitness of
      somatic mutations and infer their ancestral relationships. By quantifying both
      general clonal dynamics and newly acquired subclonal diversity, we show that 2
      distinct evolutionary patterns govern early and late relapse: on one hand, a
      highly dynamic pattern, sustained by a putative defect of DNA repair processes,
      illustrating the quick emergence of fitter clones, and on the other hand, a quasi
      inert evolution pattern, suggesting the escape from dormancy of leukemia stem
      cells likely spared from initial cytoreductive therapy. These results offer new
      insights into cALL relapse mechanisms and highlight the pressing need for adapted
      treatment strategies to circumvent resistance mechanisms.

PMID- 29365314
TI  - Factor XI contributes to myocardial ischemia-reperfusion injury in mice.

PMID- 29365316
TI  - Manipulating hemoglobin oxygenation using silica nanoparticles: a novel prospect
      for artificial oxygen carriers.
AB  - Recently, nanoparticles have attracted much attention as new scaffolds for
      hemoglobin-based oxygen carriers (HBOCs). Indeed, the development of
      bionanotechnology paves the way for the rational design of blood substitutes,
      providing that the interaction between the nanoparticles and hemoglobin at a
      molecular scale and its effect on the oxygenation properties of hemoglobin are
      finely controlled. Here, we show that human hemoglobin has a high affinity for
      silica nanoparticles, leading to the adsorption of hemoglobin tetramers on the
      surface. The adsorption process results in a remarkable retaining of the
      oxygenation properties of human adult hemoglobin and sickle cell hemoglobin,
      associated with an increase of the oxygen affinity. The cooperative oxygen
      binding exhibited by adsorbed hemoglobin and the comparison with the oxygenation
      properties of diaspirin cross-linked hemoglobin confirmed the preservation of the
      tetrameric structure of hemoglobin loaded on silica nanoparticles. Our results
      show that silica nanoparticles can act as an effector for human native and mutant
      hemoglobin. Manipulating hemoglobin oxygenation using nanoparticles opens the way
      to the design of novel HBOCs.

PMID- 29365317
TI  - Quantitative proteomics of plasma vesicles identify novel biomarkers for
      hemoglobin E/beta-thalassemic patients.
AB  - Hemoglobin E (HbE)/beta-thalassemia has a wide spectrum of clinical
      manifestations that cannot be explained purely by its genetic background.
      Circulating extracellular vesicles (EVs) are one factor that likely contributes
      to disease severity. This study has explored the differences in protein
      composition and quantity between EVs from HbE/beta-thalassemic patients and
      healthy individuals. We used tandem mass tag labeling mass spectrometry to
      analyze the EV proteins isolated from the plasma of 15 patients compared with the
      controls. To reduce biological variation between individuals, the EV proteins
      isolated from randomly assigned groups of 5 HbE/beta-thalassemic patients were
      pooled and compared with 5 pooled age- and sex-matched controls in 3 separate
      experiments. Alpha hemoglobin-stabilizing protein had the highest fold increase.
      Catalase, superoxide dismutase, T-complex proteins, heat shock proteins,
      transferrin receptor, ferritin, and cathepsin S were also upregulated in
      thalassemic circulating EVs. Importantly, haptoglobin and hemopexin were
      consistently reduced in patients' EVs across all data sets, in keeping with the
      existing hemolysis that occurs in thalassemia. The proteomic data analysis of EV
      samples isolated from 6 individual HbE/beta-thalassemic patients and western
      blotting results corroborated these findings. In conclusion, we have successfully
      identified consistent alterations of protein quantity between EVs from HbE/beta
      thalassemic and healthy individuals. This work highlights haptoglobin, hemopexin,
      and cathepsin S as potential clinically relevant biomarkers for levels of
      hemolysis and inflammation. Monitoring of these plasma proteins could help in the
      clinical management of thalassemia.

PMID- 29365319
TI  - Survival of ethnic and racial minority patients with multiple myeloma treated
      with newer medications.

PMID- 29365318
TI  - Recipient priming to one RBC alloantigen directly enhances subsequent
      alloimmunization in mice.
AB  - Individuals that become immunized to red blood cell (RBC) alloantigens can
      experience an increased rate of antibody formation to additional RBC alloantigens
      following subsequent transfusion. Despite this, how an immune response to one RBC
      immunogen may impact subsequent alloimmunization to a completely different RBC
      alloantigen remains unknown. Our studies demonstrate that Kell blood group
      antigen (KEL) RBC transfusion in the presence of inflammation induced by poly
      (I:C) (PIC) not only enhances anti-KEL antibody production through a CD4+ T-cell
      dependent process but also directly facilitates anti-HOD antibody formation
      following subsequent exposure to the disparate HOD (hen egg lysozyme, ovalbumin,
      fused to human blood group antigen Duffy b) antigen. PIC/KEL priming of the anti
      HOD antibody response required that RBCs express both the KEL and HOD antigens
      (HOD * KEL RBCs), as transfusion of HOD RBCs plus KEL RBCs or HOD RBCs alone
      failed to impact anti-HOD antibody formation in recipients previously primed with
      PIC/KEL. Transfer of CD4+ T cells from PIC/KEL-primed recipients directly
      facilitated anti-HOD antibody formation following (HOD * KEL) RBC transfusion.
      RBC alloantigen priming was not limited to PIC/KEL enhancement of anti-HOD
      alloantibody formation, as HOD-reactive CD4+ T cells enhanced anti-glycophorin A
      (anti-GPA) antibody formation in the absence of inflammation following
      transfusion of RBCs coexpressing GPA and HOD. These results demonstrate that
      immune priming to one RBC alloantigen can directly enhance a humoral response to
      a completely different RBC alloantigen, providing a potential explanation for why
      alloantibody responders may exhibit increased immune responsiveness to additional
      RBC alloantigens following subsequent transfusion.

PMID- 29365320
TI  - Poor outcome with hematopoietic stem cell transplantation for bone marrow failure
      and MDS with severe MIRAGE syndrome phenotype.

PMID- 29365322
TI  - Rivaroxaban dose adjustment using thrombin generation in severe congenital
      protein C deficiency and warfarin-induced skin necrosis.

PMID- 29365321
TI  - Immune rebound associates with a favorable clinical response to autologous HSCT
      in systemic sclerosis patients.
AB  - To evaluate the immunological mechanisms associated with clinical outcomes after
      autologous hematopoietic stem cell transplantation (AHSCT), focusing on
      regulatory T- (Treg) and B- (Breg) cell immune reconstitution, 31 systemic
      sclerosis (SSc) patients underwent simultaneous clinical and immunological
      evaluations over 36-month posttransplantation follow-up. Patients were
      retrospectively grouped into responders (n = 25) and nonresponders (n = 6),
      according to clinical response after AHSCT. Thymic function and B-cell neogenesis
      were respectively assessed by quantification of DNA excision circles generated
      during T- and B-cell receptor rearrangements. At the 1-year post-AHSCT evaluation
      of the total set of transplanted SSc patients, thymic rebound led to renewal of
      the immune system, with higher T-cell receptor (TCR) diversity, positive
      correlation between recent thymic emigrant and Treg counts, and higher expression
      of CTLA-4 and GITR on Tregs, when compared with pretransplant levels. In
      parallel, increased bone marrow output of newly generated naive B-cells, starting
      at 6 months after AHSCT, renovated the B-cell populations in peripheral blood. At
      6 and 12 months after AHSCT, Bregs increased and produced higher interleukin-10
      levels than before transplant. When the nonresponder patients were evaluated
      separately, Treg and Breg counts did not increase after AHSCT, and high TCR
      repertoire overlap between pre- and posttransplant periods indicated maintenance
      of underlying disease mechanisms. These data suggest that clinical improvement of
      SSc patients is related to increased counts of newly generated Tregs and Bregs
      after AHSCT as a result of coordinated thymic and bone marrow rebound.

PMID- 29365323
TI  - Prognostic tumor sequencing panels frequently identify germ line variants
      associated with hereditary hematopoietic malignancies.
AB  - Next-generation sequencing (NGS)-based targeted gene capture panels are used to
      profile hematopoietic malignancies to guide prognostication and treatment
      decisions. Because these panels include genes associated with hereditary
      hematopoietic malignancies (HHMs), we hypothesized that these panels could
      identify pathogenic germ line variants in malignant cells, thereby identifying
      patients at risk for HHMs. In total, pathogenic or likely pathogenic variants in
      ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, or TP53 were identified in 74 (21%) of
      360 patients. Germ line tissue was available for 24 patients with 25 pathogenic
      or likely pathogenic variants with variant allele frequencies >0.4. Six (24%) of
      these 25 variants were of germ line origin. Three DDX41 variants, 2 GATA2
      variants, and a TP53 variant previously implicated in Li-Fraumeni syndrome were
      of germ line origin. No likely pathogenic/pathogenic germ line variants possessed
      variant allele frequencies <0.4. This study demonstrates that NGS-based
      prognostic panels may identify individuals at risk for HHMs despite not being
      designed for this purpose. Furthermore, variants known to cause Li-Fraumeni
      syndrome as well as known pathogenic variants in genes such as DDX41 and GATA2
      are especially likely to be of germ line origin. Thus, tumor-based panels may
      augment, but should not replace, comprehensive germ line-based testing and
      counseling.

PMID- 29365325
TI  - Choosing for whom to recommend allogeneic transplantation for acute myeloid
      leukemia in CR1: a continued, complicated conversation.

PMID- 29365324
TI  - Expression profiling of snoRNAs in normal hematopoiesis and AML.
AB  - Small nucleolar RNAs (snoRNAs) are noncoding RNAs that contribute to ribosome
      biogenesis and RNA splicing by modifying ribosomal RNA and spliceosome RNAs,
      respectively. We optimized a next-generation sequencing approach and a custom
      analysis pipeline to identify and quantify expression of snoRNAs in acute myeloid
      leukemia (AML) and normal hematopoietic cell populations. We show that snoRNAs
      are expressed in a lineage- and development-specific fashion during
      hematopoiesis. The most striking examples involve snoRNAs located in 2 imprinted
      loci, which are highly expressed in hematopoietic progenitors and downregulated
      during myeloid differentiation. Although most snoRNAs are expressed at similar
      levels in AML cells compared with CD34+, a subset of snoRNAs showed consistent
      differential expression, with the great majority of these being decreased in the
      AML samples. Analysis of host gene expression, splicing patterns, and whole
      genome sequence data for mutational events did not identify transcriptional
      patterns or genetic alterations that account for these expression differences.
      These data provide a comprehensive analysis of the snoRNA transcriptome in normal
      and leukemic cells and should be helpful in the design of studies to define the
      contribution of snoRNAs to normal and malignant hematopoiesis.

PMID- 29365326
TI  - rRNA-gene methylation and biological aging.

PMID- 29365327
TI  - Histologic Funisitis and Likelihood of Intrauterine Inflammation or Infection: A
      Case-Control Study.
AB  - OBJECTIVE:  The objective of this study was to ascertain the likelihood of
      isolated maternal fever and suspected intrauterine inflammation or infection or
      both (Triple I) among cases of histologic chorioamnionitis with funisitis (HCF)
      at term. STUDY DESIGN:  In this case-control study, placental pathology records
      were reviewed to identify term singleton laboring patients with HCF. Controls
      (1:1) were matched for gestational age. RESULTS:  During the 6-month period,
      there were 2,399 term deliveries of laboring women. Of 1,552 (65%) term placentas
      examined, 4% (n = 60) had HCF.Features of Triple I were significantly more common
      among cases than controls: (1) isolated maternal fever of >=100.4 degrees F,
      twice, at least 30 minutes apart (p = 0.014); (2) fever with fetal tachycardia (p
      = 0.029); 3) fever with either fetal tachycardia or white blood cell count
      greater than 15,000 per mm3 (p = 0.034). The feature of Triple I with the highest
      sensitivity at 10% (95% confidence intervals [CI] 4-21%) was isolated maternal
      fever using >=100.4 degrees F on two occasions. The specificity for all features
      was consistently 100% (95% CI 91-100%). CONCLUSION:  To our knowledge, this is
      the first report on HCF and Triple I features. Though the sensitivity of Triple I
      to identify HCF is low, specificity is excellent.

PMID- 29365328
TI  - Outcomes of Spontaneous Labor in Women Undergoing Trial of Labor after Cesarean
      as Compared with Nulliparous Women: A Retrospective Cohort Study.
AB  - OBJECTIVE:  The objective of this study was to compare spontaneous labor outcomes
      in women undergoing trial of labor after cesarean (TOLAC) and nulliparas to
      better counsel women. STUDY DESIGN:  A 4-year retrospective cohort. We included
      women at term in spontaneous labor with vertex singletons and no more than one
      prior cesarean delivery. In planned secondary analysis, we focused on a subset of
      women with a prior cesarean and a predicted likelihood of a successful vaginal
      delivery of 70% or more based on the Maternal-Fetal Medicine Units-vaginal birth
      after cesarean (VBAC) calculator. RESULTS:  Our cohort included 606 TOLACS and
      606 nulliparas. Women undergoing TOLAC were more likely to undergo cesarean
      delivery (25.7 vs. 14.7%; p < 0.001). Severe maternal hemorrhage (1.5 vs. 0.2%; p
      = 0.02) and uterine rupture (1.9 vs. 0.0%; p < 0.01) were more likely in the
      TOLAC group. For the subset of women with a predicted likelihood of VBAC of 70%
      or more, there were no differences in cesarean delivery (16.7 vs. 14.7%; p =
      0.51), maternal, or immediate neonatal complications. CONCLUSION:  Women
      undergoing TOLAC were more likely to have a cesarean delivery, hemorrhage, or
      uterine rupture. Those with more than 70% predicted likelihood of VBAC were no
      more likely to experience these outcomes. These findings help contextualize the
      risks of TOLAC for women considering this option.

PMID- 29365329
TI  - The Relationship between Body Mass Index in Pregnancy and Adverse Maternal,
      Perinatal, and Neonatal Outcomes in Rural India and Pakistan.
AB  - OBJECTIVE:  The objective of this study was to describe the relationship between
      early pregnancy body mass index (BMI) and maternal, perinatal, and neonatal
      outcomes in rural India and Pakistan. STUDY DESIGN:  In a prospective, population
      based pregnancy registry implemented in communities in Thatta, Pakistan and
      Nagpur and Belagavi, India, we obtained women's BMI prior to 12 weeks' gestation
      (categorized as underweight, normal, overweight, and obese following World Health
      Organization criteria). Outcomes were assessed 42 days postpartum. RESULTS:  The
      proportion of women with an adverse maternal outcome increased with increasing
      maternal BMI. Less than one-third of nonoverweight/nonobese women, 47.2% of
      overweight women, and 56.0% of obese women experienced an adverse maternal
      outcome. After controlling for site, maternal age and parity, risks of
      hypertensive disease/severe preeclampsia/eclampsia, cesarean/assisted delivery,
      and antibiotic use were higher among women with higher BMIs. Overweight women
      also had significantly higher risk of perinatal and early neonatal mortality
      compared with underweight/normal BMI women. Overweight women had a significantly
      higher perinatal mortality rate. CONCLUSION:  High BMI in early pregnancy was
      associated with increased risk of adverse maternal, perinatal, and neonatal
      outcomes in rural India and Pakistan. These findings present an opportunity to
      inform efforts for women to optimize weight prior to conception to improve
      pregnancy outcomes.

PMID- 29365330
TI  - Is Uterocervical Angle Associated with Gestational Latency after Physical Exam
      Indicated Cerclage?
AB  - OBJECTIVE:  Prediction of gestational latency after placement of physical exam
      indicated cerclage (PEIC) is limited. Uterocervical angle (UCA) has been
      associated with spontaneous preterm delivery in the general population. Our
      objective was to examine whether UCA is associated with gestational latency in
      women with PEIC. STUDY DESIGN:  This retrospective cohort included women with a
      singleton gestation who had PEIC placed at a single tertiary care center between
      January 2010 and September 2015. Ultrasound images of the cervix obtained prior
      to placement of PEIC were reviewed. Spearman's correlation coefficient for the
      relationship between UCA and gestational latency was estimated. UCA was
      dichotomized at 95 degrees  and 105 degrees . Survival analyses were performed
      and Cox proportional hazard ratios were calculated. RESULTS:  Sixty women met the
      inclusion criteria. Median gestational latency was 93 days (IQR 39-121 d). There
      was no significant correlation between UCA and gestational latency (Spearman's
      rho 0.08, p = 0.54). Survival analyses demonstrated no significant difference in
      gestational latency stratified by UCA >= 95 degrees  (HR 1.19, 95% CI 0.70-2.04)
      or UCA >= 105 degrees  (HR 0.95, 95% CI 0.56-1.63). Findings persisted after
      adjusting for potential confounders (aHR 1.29, 95% CI 0.74-2.23 for UCA >= 95
      degrees  and aHR 1.04, 95% CI 0.60-1.82). CONCLUSION:  UCA is not associated with
      gestational latency in women with PEIC.

PMID- 29365331
TI  - ?

PMID- 29365332
TI  - Cardiovascular Risk Factors in Acromegaly: What's the Impact of Disease Control?
AB  - OBJECTIVE: Cardiovascular disease is one of the most important causes of death in
      acromegalic patients. The aim of this study is to compare the prevalence of
      cardiovascular risk factors among acromegalic patients and to evaluate the impact
      of disease control on these factors. MATERIAL AND METHODS: 11 acromegalic
      patients with active disease and 12 controlled patients were evaluated for blood
      pressure, body mass index, glucose, coagulation status, and lipid profile. A
      group of 11 patients with non-functioning pituitary adenomas was used as control
      population. RESULTS: Significant differences were found in lipid profile, glucose
      and coagulation status in both active and controlled patients. Higher levels of
      fasting glucose (151.2+/-102.5 mg/dL, p=0.05 and 108.3+/-23.4 mg/dL, p=0.02 for
      active and controlled patients respectively) and fibrinogen (427.1+/-61.9 mg/dL,
      p=0.02 and 437.3+/-106.6 mg/dL, p=0.04 for active and controlled patients
      respectively) were present in both acromegalic groups. Active patients had higher
      levels of antithrombin III (1.1+/-0.1 U/mL, p=0.005) and the controlled ones had
      higher levels of high density lipoprotein cholesterol (56.1+/-12.5 mg/dL,
      p=0.05), compared with the non-functioning group. The differences between active
      and controlled acromegalic patients are that the latter have reduced total
      cholesterol (170.4+/-31.7 vs 201.7+/-34.6 mg/dL, p=0.02), lower density
      lipoprotein cholesterol (96,8+/-25,2 vs 130.8+/-31.5 mg/dL, p=0.01) and
      antithrombin III (1.0+/-0.2 vs 1.1+/-0.1 U/mL, p=0.05). CONCLUSION: There is some
      reduction in cardiovascular risk factors with control of the disease, but
      possibly without the return to basal levels.

PMID- 29365333
TI  - Effects of Coenzyme Q10 Supplementation on Serum Values of Gamma-glutamyl
      transferase, Pseudocholinesterase, Bilirubin, Ferritin, and High-Sensitivity C
      Reactive Protein in Women with Type 2 Diabetes.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a disease associated with
      increased oxidative stress which results from mitochondrial dysfunction. Coenzyme
      Q10 (CoQ10) is an essential antioxidant for energy production in mitochondria.
      The purpose of this randomized double-blind clinical trial study was to evaluate
      the effects of CoQ10 supplementation on serum values of gamma-glutamyl
      transferase (GGT), pseudocholinesterase (PchE), bilirubin, ferritin, and high
      sensitivity c-reactive protein (hs-CRP) and metabolic syndrome biomarkers in
      women with T2DM. MATERIAL & METHODS: Eighty women with T2DM enrolled in this
      study. Thirty six of them were randomized in the drug group (receiving 100 mg/day
      of CoQ10) and 44 women were randomized in placebo group. Intervention was
      continued for 12 weeks. In both groups 35 subjects finished the study and were
      included in the analysis. Serum levels of the variables were measured before and
      after supplementation. RESULTS: Serum values of FBS (P=0.039), HOMA-IR (P=0.01),
      ferritin (P<0.001), total cholesterol (TC) (P=0.006), LDL-C (P=0.007) decreased
      and HDL-C (P=0.02) increased significantly in the drug group after intervention.
      Serum levels of triglyceride (P=0.09) decreased marginally in CoQ10 group.
      CONCLUSIONS: The results of the current study had shown that after
      supplementation with 100 mg/day of CoQ10 for 12 weeks, serum values of FBS, HOMA
      IR, TC, LDL-C and ferritin were decreased and values of HDL-C were increased in
      women with T2DM.

PMID- 29365334
TI  - Berberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4
      Signaling Pathway.
AB  - Berberine, a natural compound extracted from several Chinese herbs including
      Coptis chinensis, has been shown to have anti-obesity effects and prevents
      insulin resistance in high-fat diet (HFD)-fed obese rats by modulating the gut
      microbiota; however, the molecular mechanisms underlying these activities remain
      unknown. We investigated the effects of berberine on obesity and insulin
      resistance by examining the lipopolysaccharide (LPS)/toll-like receptor 4
      (TLR4)/tumor necrosis factor (TNF)-alpha signaling pathway in livers of HFD-fed
      obese rats. Our results showed that 8-week berberine (200 mg/kg) treatment
      significantly reduced fasting blood glucose, triglyceride, low-density
      lipoprotein-cholesterol and insulin resistance in HFD-fed obese rats. However,
      berberine had no significant effects on body weight, visceral fat mass or the
      visceral fat to body weight ratio. Berberine also attenuated HFD-induced hepatic
      steatosis. A prolonged HFD altered the gut microbiota composition by reducing
      protective bacteria like Bifidobacterium and increasing gram negative bacteria
      like Escherichia coli, which resulted in increased LPS release into plasma.
      Berberine reversed these effects and inhibited LPS-induced TLR4/TNF-alpha
      activation, resulting in increased insulin receptor and insulin receptor
      substrate-1 expression in the liver. These findings suggested that berberine may
      reduce insulin resistance, at least in part by modulating the gut microbiota
      along with inhibiting LPS/TLR4/TNF-alpha signaling in the liver.

PMID- 29365335
TI  - Screening for Hypogonadism in Primary Healthcare: How to do this Effectively.
AB  - BACKGROUND: Testosterone, the most important androgen produced by the testes,
      plays an integral role in male health. Testosterone levels are increasingly being
      checked in primary healthcare as awareness of the risks of male hypogonadism
      grows. AIM: To investigate what tests are performed to screen for hypogonadism
      and to exclude secondary hypogonadism. DESIGN AND SETTING: All participants
      attended general practices in the UK. METHODS: Data search was performed using
      the EMIS(r): clinical database (provider of the majority of GP operating systems
      in Cheshire). The anonymised records of male patients aged 18-98 years who had
      undergone a check of serum testosterone during a 10-year period were analysed.
      RESULTS: Overall screening rate was 4.3%. Of 8 788 men with a testosterone
      result, 1 924 men (21.9%) had a total testosterone level <10 nmol/L. Just 689 of
      8 788 men (7.8%) had a sex hormone-binding globulin (SHBG) result, corresponding
      to 30.5% of those potentially hypogonadal. Estimated free testosterone was
      negatively associated with BMI (Spearman's rho -0.2, p<0.001) as was total
      testosterone in the over 50 s. Of 1 924 potentially hypogonadal men with a serum
      testosterone <10 nmol/L, 588 of 1 924 (30.6%) had a check of serum prolactin.
      46.3% and 41.7% had LH and FSH measured, respectively. Only 19.1% of 1 924 men
      with a hypogonadal total testosterone level were subsequently put on testosterone
      replacement. The percentage of men in the relatively socially disadvantaged
      category was similar for both eugonadal and hypogonadal men with a much higher
      rate of screening for hypogonadism in more socially advantaged men. CONCLUSIONS:
      Screening in primary healthcare identified a significant minority of men who had
      potential hypogonadism. Interpretation of a low serum testosterone requires
      measurement of serum prolactin, LH and FSH in order to rule out secondary
      hypogonadism. We suggest that this becomes part of routine screening with a
      balanced screening approach across the socioeconomic spectrum.

PMID- 29365337
TI  - Muscle Oxygenation Responses to Low-intensity Steady Rate Concentric and
      Eccentric Cycling.
AB  - Muscle deoxygenation responses provide information about the training impulse of
      an exercise session enabling adaptation to be predicted. Our aim was to
      investigate muscle oxygenation profiles during prolonged low-intensity eccentric
      and concentric cycling. Twelve healthy men performed two 45-min exercise sessions
      of concentric (CON) and eccentric (ECC) cycling, matched for the same heart rate
      at the start of each session. Mechanical power output during ECC was ~2.5 times
      that of CON (210+/-40 W vs. 82+/-16 W). Oxygen uptake, blood lactate, cardiac
      output and systolic arterial pressure responses did not differ between exercises.
      Heart rate was similar at 5 min of each exercise bout but progressively increased
      during ECC and was higher at 15, 30 and 45 min of ECC compared to CON (+10 bpm),
      with a trend for a lower stroke volume. Diastolic and mean blood pressures were
      higher during ECC. No significant differences were observed in muscle oxygenation
      profiles. Muscle oxygenation responses during prolonged low-intensity exercise
      were not affected by the type of muscle action at the same metabolic demand and
      cardiac output.

PMID- 29365339
TI  - Confirming Maximal Oxygen Uptake: Is Heart Rate the Answer?
AB  - This study investigates heart rate (HR), in 11 young adults (22.4+/-3.21yr), at
      VO2max, to ascertain whether measured maximal heart rate (HRmax), as determined
      by a plateau in HR (HRplat), can reliably confirm VO2max. VO2max and HRplat were
      determined, using the parameters of a VO2<=50 ml*min-1 and a ?HR<=2b*min-1,
      respectively, over the final 60 s of sampling. VO2 was also independently
      determined using a verification phase protocol. A HRplat was achieved by 91% of
      participants (?HR=1.3+/-1b*min-1) and critically the time at which HRmax was
      reached coincided with that at which VO2max was achieved. Moreover RER and
      DeltaRER criteria were reached significantly earlier (p<0.05) than VO2max, whilst
      age-related heart rate maximums (HRage), were not achieved by many participants.
      The results suggest that a HRplat <=2 b*min-1 is a more accurate method, within
      the group tested, to determine whether a 'true' VO2max has been achieved, than
      other secondary criteria and potentially avoids the requirement for an additional
      verification phase.

PMID- 29365338
TI  - Muscle Thickness and Passive Muscle Stiffness in Elite Athletes: Implications of
      the Effect of Long-Term Daily Training on Skeletal Muscle.
AB  - To examine the effect of long-term daily training on athletes' skeletal muscle,
      this study determined the relation between their muscle thickness and passive
      muscle stiffness, and compared the muscle thickness and muscle stiffness between
      athletes and non-athletes. Participants were elite Japanese athletes (278 men,
      200 women) from various sports and non-athletes (35 men, 35 women). Rectus
      femoris (RF) muscle thickness was measured using B-mode ultrasonography and was
      normalized to the total body mass (muscle thickness/body mass1/3). RF passive
      muscle stiffness (shear modulus) was assessed by ultrasound shear-wave
      elastography. There was a negligibly significant correlation between muscle
      thickness and muscle stiffness in male athletes (p=0.003; r=-0.18) but not in
      female athletes (p=0.764; r=0.02). Among men, muscle thickness was significantly
      greater in athletes than non-athletes (p<0.001), whereas muscle stiffness was
      significantly less in athletes than non-athletes (p=0.020). Among women, muscle
      thickness was significantly greater in athletes than non-athletes (p<0.001),
      whereas muscle stiffness did not differ significantly between athletes and non
      athletes (p=0.412). These results suggest that the effect of long-term daily
      training performed by athletes on muscle stiffness is more complicated than that
      on muscle thickness.

PMID- 29365340
TI  - Towards Implementation of OMOP in a German University Hospital Consortium.
AB  - BACKGROUND: In 2015, the German Federal Ministry of Education and Research
      initiated a large data integration and data sharing research initiative to
      improve the reuse of data from patient care and translational research. The
      Observational Medical Outcomes Partnership (OMOP) common data model and the
      Observational Health Data Sciences and Informatics (OHDSI) tools could be used as
      a core element in this initiative for harmonizing the terminologies used as well
      as facilitating the federation of research analyses across institutions.
      OBJECTIVE: To realize an OMOP/OHDSI-based pilot implementation within a
      consortium of eight German university hospitals, evaluate the applicability to
      support data harmonization and sharing among them, and identify potential
      enhancement requirements. METHODS: The vocabularies and terminological mapping
      required for importing the fact data were prepared, and the process for importing
      the data from the source files was designed. For eight German university
      hospitals, a virtual machine preconfigured with the OMOP database and the OHDSI
      tools as well as the jobs to import the data and conduct the analysis was
      provided. Last, a federated/distributed query to test the approach was executed.
      RESULTS: While the mapping of ICD-10 German Modification succeeded with a rate of
      98.8% of all terms for diagnoses, the procedures could not be mapped and hence an
      extension to the OMOP standard terminologies had to be made.Overall, the data of
      3 million inpatients with approximately 26 million conditions, 21 million
      procedures, and 23 million observations have been imported.A federated query to
      identify a cohort of colorectal cancer patients was successfully executed and
      yielded 16,701 patient cases visualized in a Sunburst plot. CONCLUSION:
      OMOP/OHDSI is a viable open source solution for data integration in a German
      research consortium. Once the terminology problems can be solved, researchers can
      build on an active community for further development.

PMID- 29365341
TI  - Improving the Accuracy of a Clinical Decision Support System for Cervical Cancer
      Screening and Surveillance.
AB  - BACKGROUND: Clinical decision support systems (CDSS) for cervical cancer
      prevention are generally limited to identifying patients who are overdue for
      their next routine/next screening, and they do not provide recommendations for
      follow-up of abnormal results. We previously developed a CDSS to automatically
      provide follow-up recommendations based on the American Society of Colposcopy and
      Cervical Pathology (ASCCP) guidelines for women with both previously normal and
      abnormal test results leveraging information available in the electronic medical
      record (EMR). OBJECTIVE: Enhance the CDSS by improving its accuracy and
      incorporating changes to reflect the latest revision of the guidelines. METHODS:
      After making enhancements to the CDSS, we evaluated the performance of the
      clinical recommendations on 393 patients selected through stratified sampling
      from a set of 3,704 patients in a nonclinical setting. We performed chart review
      of individual patient's record to evaluate the performance of the system. An
      expert clinician assisted by a resident manually reviewed the recommendation made
      by the system and verified whether the recommendations were as per the ASCCP
      guidelines. RESULTS: The recommendation accuracy of the enhanced CDSS improved to
      93%, which is a substantial improvement over the 84% reported previously. A
      detailed analysis of errors is presented in this article. We fixed the errors
      identified in this evaluation that were amenable to correction to further improve
      the accuracy of the system. The source code of the updated CDSS is available at
      https://github.com/ohnlp/MayoNlpPapCdss. CONCLUSION: We made substantial
      enhancements to our earlier prototype CDSS with the updated ASCCP guidelines and
      performed a thorough evaluation in a nonclinical setting to improve the accuracy
      of the CDSS. The CDSS will be further refined as it is utilized in the practice.

PMID- 29365342
TI  - Improving estimation and prediction in linear regression incorporating external
      information from an established reduced model.
AB  - We consider a situation where there is rich historical data available for the
      coefficients and their standard errors in a linear regression model describing
      the association between a continuous outcome variable Y and a set of predicting
      factors X, from a large study. We would like to use this summary information for
      improving inference in an expanded model of interest, Y given X,B. The additional
      variable B is a new biomarker, measured on a small number of subjects in a new
      dataset. We formulate the problem in an inferential framework where the
      historical information is translated in terms of nonlinear constraints on the
      parameter space and propose both frequentist and Bayes solutions to this problem.
      We show that a Bayesian transformation approach proposed by Gunn and Dunson is a
      simple and effective computational method to conduct approximate Bayesian
      inference for this constrained parameter problem. The simulation results
      comparing these methods indicate that historical information on E(Y|X) can
      improve the efficiency of estimation and enhance the predictive power in the
      regression model of interest E(Y|X,B). We illustrate our methodology by enhancing
      a published prediction model for bone lead levels in terms of blood lead and
      other covariates, with a new biomarker defined through a genetic risk score.

PMID- 29365343
TI  - Extracorporeal liver assist device for alcoholic hepatitis: A potential silver
      lining?

PMID- 29365344
TI  - Dystrophinopathy muscle biopsies in the genetic testing ERA: One center's data.
AB  - INTRODUCTION: Comprehensive genetic testing for dystrophinopathy can detect ~95%
      of pathogenic variants in the dystrophin gene (DMD) and is often the preferred
      diagnostic approach. METHODS: We reviewed pathology reports for muscle biopsies
      evaluated at the University of Iowa with a pathological diagnosis of
      dystrophinopathy based on dystrophic histopathology and abnormal
      immunofluorescence staining: reduced to absent dystrophin, expression of
      utrophin, and loss of neuronal nitric oxide synthase. RESULTS: The percentage of
      muscle biopsies with dystrophinopathy has been stable since 1997. Among 2,298
      biopsies evaluated between 2011 and 2016, 72 (3.1%) had pathologic features of
      dystrophinopathy. Median age at biopsy was 8 years (range, 0.66-84). Half had
      undergone DMD genetic testing prior to biopsy. Clinical phenotypes recorded on
      requisitions were typical of muscular dystrophy for 57 (79%) biopsies.
      DISCUSSION: Muscle biopsy continues to play an important role in the diagnosis of
      dystrophinopathy, particularly in patients with later symptom onset,
      comorbidities, or normal DMD genetic testing results. Muscle Nerve, 2018.

PMID- 29365345
TI  - Reply.

PMID- 29365346
TI  - Interventions for increasing fruit and vegetable consumption in children aged
      five years and under.
AB  - BACKGROUND: Insufficient consumption of fruits and vegetables in childhood
      increases the risk of future chronic diseases, including cardiovascular disease.
      OBJECTIVES: To assess the effectiveness, cost effectiveness and associated
      adverse events of interventions designed to increase the consumption of fruit,
      vegetables or both amongst children aged five years and under. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the
      Cochrane Library, MEDLINE and Embase to identify eligible trials on 25 September
      2017. We searched Proquest Dissertations and Theses and two clinical trial
      registers in November 2017. We reviewed reference lists of included trials and
      handsearched three international nutrition journals. We contacted authors of
      included studies to identify further potentially relevant trials. SELECTION
      CRITERIA: We included randomised controlled trials, including cluster-randomised
      controlled trials and cross-over trials, of any intervention primarily targeting
      consumption of fruit, vegetables or both among children aged five years and
      under, and incorporating a dietary or biochemical assessment of fruit or
      vegetable consumption. Two review authors independently screened titles and
      abstracts of identified papers; a third review author resolved disagreements.
      DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and
      assessed the risks of bias of included studies; a third review author resolved
      disagreements. Due to unexplained heterogeneity, we used random-effects models in
      meta-analyses for the primary review outcomes where we identified sufficient
      trials. We calculated standardised mean differences (SMDs) to account for the
      heterogeneity of fruit and vegetable consumption measures. We conducted
      assessments of risks of bias and evaluated the quality of evidence (GRADE
      approach) using Cochrane procedures. MAIN RESULTS: We included 55 trials with 154
      trial arms and 11,108 participants. Thirty-three trials examined the impact of
      child-feeding practices (e.g. repeated food exposure) in increasing child
      vegetable intake. Thirteen trials examined the impact of parent nutrition
      education in increasing child fruit and vegetable intake. Eight studies examined
      the impact of multicomponent interventions (e.g. parent nutrition education and
      preschool policy changes) in increasing child fruit and vegetable intake. One
      study examined the effect of a nutrition intervention delivered to children in
      increasing child fruit and vegetable intake.We judged 14 of the 55 included
      trials as free from high risks of bias across all domains; performance, detection
      and attrition bias were the most common domains judged at high risk of bias for
      the remaining studies.Meta-analysis of trials examining child-feeding practices
      versus no intervention revealed a positive effect on child vegetable consumption
      (SMD 0.38, 95% confidence interval (CI) 0.15 to 0.61; n = 1509; 11 studies; very
      low-quality evidence), equivalent to a mean difference of 4.03 g of vegetables.
      There were no short-term differences in child consumption of fruit and vegetables
      in meta-analyses of trials examining parent nutrition education versus no
      intervention (SMD 0.11, 95% CI -0.05 to 0.28; n = 3023; 10 studies; very low
      quality evidence) or multicomponent interventions versus no intervention (SMD
      0.28, 95% CI -0.06 to 0.63; n = 1861; 4 studies; very low-quality
      evidence).Insufficient data were available to assess long-term effectiveness,
      cost effectiveness and unintended adverse consequences of interventions. Studies
      reported receiving governmental or charitable funds, except for three studies
      reporting industry funding. AUTHORS' CONCLUSIONS: Despite identifying 55 eligible
      trials of various intervention approaches, the evidence for how to increase
      children's fruit and vegetable consumption remains sparse. There was very low
      quality evidence that child-feeding practice interventions are effective in
      increasing vegetable consumption in children aged five years and younger, however
      the effect size was very small and long-term follow-up is required. There was
      very low-quality evidence that parent nutrition education and multicomponent
      interventions are not effective in increasing fruit and vegetable consumption in
      children aged five years and younger. All findings should be considered with
      caution, given most included trials could not be combined in meta-analyses. Given
      the very low-quality evidence, future research will very likely change estimates
      and conclusions. Such research should adopt more rigorous methods to advance the
      field.This is a living systematic review. Living systematic reviews offer a new
      approach to review updating, in which the review is continually updated,
      incorporating relevant new evidence as it becomes available. Please refer to the
      Cochrane Database of Systematic Reviews for the current status of this review.

PMID- 29365347
TI  - Whole brain radiotherapy for the treatment of newly diagnosed multiple brain
      metastases.
AB  - BACKGROUND: This is an update to the review published in the Cochrane Library
      (2012, Issue 4).It is estimated that 20% to 40% of people with cancer will
      develop brain metastases during the course of their illness. The burden of brain
      metastases impacts quality and length of survival. OBJECTIVES: To assess the
      effectiveness and adverse effects of whole brain radiotherapy (WBRT) given alone
      or in combination with other therapies to adults with newly diagnosed multiple
      brain metastases. SEARCH METHODS: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, and Embase to May 2017 and the National
      Cancer Institute Physicians Data Query for ongoing trials. SELECTION CRITERIA: We
      included phase III randomised controlled trials (RCTs) comparing WBRT versus
      other treatments for adults with newly diagnosed multiple brain metastases. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality
      and abstracted information in accordance with Cochrane methods. MAIN RESULTS: We
      added 10 RCTs to this updated review. The review now includes 54 published trials
      (45 fully published reports, four abstracts, and five subsets of data from
      previously published RCTs) involving 11,898 participants.Lower biological WBRT
      doses versus controlThe hazard ratio (HR) for overall survival (OS) with lower
      biological WBRT doses as compared with control (3000 cGy in 10 daily fractions)
      was 1.21 (95% confidence interval (CI) 1.04 to 1.40; P = 0.01; moderate-certainty
      evidence) in favour of control. The HR for neurological function improvement
      (NFI) was 1.74 (95% CI 1.06 to 2.84; P = 0.03; moderate-certainty evidence) in
      favour of control fractionation.Higher biological WBRT doses versus controlThe HR
      for OS with higher biological WBRT doses as compared with control (3000 cGy in 10
      daily fractions) was 0.97 (95% CI 0.83 to 1.12; P = 0.65; moderate-certainty
      evidence). The HR for NFI was 1.14 (95% CI 0.92 to 1.42; P = 0.23; moderate
      certainty evidence).WBRT and radiosensitisersThe addition of radiosensitisers to
      WBRT did not confer additional benefit for OS (HR 1.05, 95% CI 0.99 to 1.12; P =
      0.12; moderate-certainty evidence) or for brain tumour response rates (odds ratio
      (OR) 0.84, 95% CI 0.63 to 1.11; P = 0.22; high-certainty evidence).Radiosurgery
      and WBRT versus WBRT aloneThe HR for OS with use of WBRT and radiosurgery boost
      as compared with WBRT alone for selected participants was 0.61 (95% CI 0.27 to
      1.39; P = 0.24; moderate-certainty evidence). For overall brain control at one
      year, the HR was 0.39 (95% CI 0.25 to 0.60; P < 0.0001; high-certainty evidence)
      favouring the WBRT and radiosurgery boost group.Radiosurgery alone versus
      radiosurgery and WBRTThe HR for local brain control was 2.73 (95% CI 1.87 to
      3.99; P < 0.00001; high-certainty evidence)favouring the addition of WBRT to
      radiosurgery. The HR for distant brain control was 2.34 (95% CI 1.73 to 3.18; P <
      0.00001; high-certainty evidence) favouring WBRT and radiosurgery. The HR for OS
      was 1.00 (95% CI 0.80 to 1.25; P = 0.99; moderate-certainty evidence). Two trials
      reported worse neurocognitive outcomes and one trial reported worse quality of
      life outcomes when WBRT was added to radiosurgery.We could not pool data from
      trials related to chemotherapy, optimal supportive care (OSC), molecular targeted
      agents, neurocognitive protective agents, and hippocampal sparing WBRT. However,
      one trial reported no differences in quality-adjusted life-years for selected
      participants with brain metastases from non-small-cell lung cancer randomised to
      OSC and WBRT versus OSC alone. AUTHORS' CONCLUSIONS: None of the trials with
      altered higher biological WBRT dose-fractionation schemes reported benefit for
      OS, NFI, or symptom control compared with standard care. However, OS and NFI were
      worse for lower biological WBRT dose-fractionation schemes than for standard dose
      schedules.The addition of WBRT to radiosurgery improved local and distant brain
      control in selected people with brain metastases, but data show worse
      neurocognitive outcomes and no differences in OS.Selected people with multiple
      brain metastases from non-small-cell lung cancer may show no difference in OS
      when OSC is given and WBRT is omitted.Use of radiosensitisers, chemotherapy, or
      molecular targeted agents in conjunction with WBRT remains experimental.Further
      trials are needed to evaluate the use of neurocognitive protective agents and
      hippocampal sparing with WBRT. As well, future trials should examine homogeneous
      participants with brain metastases with focus on prognostic features and
      molecular markers.

PMID- 29365348
TI  - Volumetric muscle loss: Including nerves into the equation.

PMID- 29365349
TI  - Transdifferentiation of adipocytes to osteoblasts: potential for orthopaedic
      treatment.
AB  - OBJECTIVES: As both adipocytes and osteoblasts originate from the same pool of
      mesenchymal stem cells, increasing clinical evidence has emerged of the
      plasticity between the two lineages. For instance, the downregulation of
      osteoblast differentiation and upregulation of adipogenesis are common features
      of conditions such as multiple myeloma, obesity and drug-induced bone loss in
      diabetes mellitus. However, despite in-vitro and in-vivo observations of
      adipocyte transdifferentiation into osteoblasts, little is known of the
      underlying mechanisms. KEY FINDINGS: This review summarises the current knowledge
      of this particular transdifferentiation process whereby the Wnt/beta-catenin
      signalling pathway and Runx2 overexpression have been postulated to play a
      critical role. SUMMARY: Furthermore, due to the possibility of a novel therapy in
      the treatment of bone conditions, a number of agents with the potential to induce
      adipo-to-osteoblast transdifferentiation have been investigated such as all-trans
      retinoic acid, bone morphogenetic protein-9 and vascular endothelial growth
      factor.

PMID- 29365350
TI  - Transforaminal lumbar puncture for intrathecal nusinersen administration.

PMID- 29365352
TI  - Lambert-Eaton myasthenic syndrome and cerebellar ataxia: is Response to
      immunotherapy a clue to pathogenesis?

PMID- 29365351
TI  - Effect of Vascepa (icosapent ethyl) on progression of coronary atherosclerosis in
      patients with elevated triglycerides (200-499 mg/dL) on statin therapy: Rationale
      and design of the EVAPORATE study.
AB  - Despite reducing progression and promoting regression of coronary
      atherosclerosis, statin therapy does not fully address residual cardiovascular
      (CV) risk. High-purity eicosapentaenoic acid (EPA) added to a statin has been
      shown to reduce CV events and induce regression of coronary atherosclerosis in
      imaging studies; however, data are from Japanese populations without high
      triglyceride (TG) levels and baseline EPA serum levels greater than those in
      North American populations. Icosapent ethyl is a high-purity prescription EPA
      ethyl ester approved at 4 g/d as an adjunct to diet to reduce TG levels in adults
      with TG levels >499 mg/dL. The objective of the randomized, double-blind, placebo
      controlled EVAPORATE study is to evaluate the effects of icosapent ethyl 4 g/d on
      atherosclerotic plaque in a North American population of statin-treated patients
      with coronary atherosclerosis, TG levels of 200 to 499 mg/dL, and low-density
      lipoprotein cholesterol levels of 40 to 115 mg/dL. The primary endpoint is change
      in low-attenuation plaque volume measured by multidetector computed tomography
      angiography. Secondary endpoints include incident plaque rates; quantitative
      changes in different plaque types and morphology; changes in markers of
      inflammation, lipids, and lipoproteins; and the relationship between these
      changes and plaque burden and/or plaque vulnerability. Approximately 80 patients
      will be followed for 9 to 18 months. The clinical implications of icosapent ethyl
      4 g/d treatment added to statin therapy on CV endpoints are being evaluated in
      the large CV outcomes study REDUCE-IT. EVAPORATE will provide important imaging
      derived data that may add relevance to the clinically derived outcomes from
      REDUCE-IT.

PMID- 29365353
TI  - Can available mathematical models predict serum digoxin levels in Thai patients?
AB  - WHAT IS KNOWN AND OBJECTIVE: Digoxin is commonly prescribed for heart failure
      patients with reduced ejection fraction (HFrEF) and patients with atrial
      fibrillation (AF). Due to digoxin's narrow therapeutic range, monitoring the
      serum digoxin concentration (SDC) is important. However, the SDC measurement is
      not widely available. Equations using clinical parameters can be employed to
      estimate the SDC but have never been studied in the Thai population. Therefore,
      we conducted this study to evaluate the correlation between the measured SDC and
      predicted digoxin level using 2 commonly used equations: the Konishi equation and
      the Koup and Jusko equation. METHODS: This report describes prospective, cross
      sectional study conducted at Chiang Mai University. One hundred and fourteen
      patients were recruited in the study. All of the patients were diagnosed as
      having HFrEF, AF or both and had been receiving digoxin for at least 4 weeks. The
      SDC of each patient was measured at steady state and assigned to one of 3 groups
      according to the classifications of the Digitalis Investigation Group (DIG)
      trial: in the therapeutic range, over the therapeutic range and in the suboptimal
      range. RESULTS AND DISCUSSION: There were significant correlations between the
      measured and predicted SDCs using both the Konishi equation and the Koup and
      Jusko equation, which had correlation coefficients (R) of 0.69 and 0.31 (P < .05
      for both), respectively. The percentages of patients with measured SDCs in the
      therapeutic range, over the therapeutic range and in the suboptimal range were
      27.2%, 9.6% and 63.2%, respectively. The sensitivity and specificity of the
      Konishi equation in predicting SDCs in the over the therapeutic range were 72.73%
      (95% Confidence interval (CI): 39.03%-93.98%) and 80.58% (95% CI: 71.62%-87.72%),
      respectively. Of the 5 patients (4.4%) who were rehospitalized, 2 patients
      (0.01%) were readmitted due to acute decompensated heart failure (ADHF). One of
      the patients had an SDC that was over the therapeutic range. None of the
      readmitted patients had ventricular arrhythmia. WHAT IS NEW AND CONCLUSIONS: The
      Konishi equation yielded better predictions of the SDC, especially in the
      subgroup of HFrEF patients. Furthermore, the prediction of SDCs in the over the
      therapeutic range using this equation was superior to that of the Koup and Jusko
      equation. With further validation in a larger population, this equation should
      facilitate the detection of patients who are over the therapeutic range in
      clinical practice.

PMID- 29365354
TI  - Leg muscle MRI in identical twin boys with duchenne muscular dystrophy.

PMID- 29365355
TI  - Comprehensive drug utilization review in neonates: liposomal amphotericin B.
AB  - OBJECTIVES: This drug utilization evaluation aims to review current evidence on
      safety and efficacy of using liposomal amphotericin B (LAMB) in newborns with
      candidiasis, and compare it to the conventional preparation. Conventional
      amphotericin B deoxycholate (DAMB) is more commonly used in newborns, but dose
      limiting adverse effects may compromise its efficacy. This review will examine
      the advantages and disadvantages of liposomal amphotericin B and define its place
      in current practice. KEY FINDINGS: The terms 'AmBisome' or 'liposomal
      amphotericin B' and 'neonatal candidiasis' were entered in both PubMed and Ovid;
      studies included focused on safety and efficacy of liposomal amphotericin B in
      newborns with candidiasis, as well as studies comparing the conventional and the
      liposomal formulations in newborns as monotherapy. Pertinent references obtained
      from this search were also included. Additionally, pharmacokinetic studies were
      reviewed to include available data on dosing. Single case reports were not
      included in the review due to the limited conclusions that can be drawn from such
      sample sizes and quality of data. SUMMARY: Although liposomal amphotericin B may
      be better tolerated and as efficacious as the conventional formulation based on
      the published literature, the weakness of the studies available on the subject
      cannot be overlooked. Additional randomized controlled trials are needed to
      determine the true benefits of this medication.

PMID- 29365356
TI  - Treatment for hepatitis delta virus with the prenylation inhibitor lonafarnib:
      It's getting closer.

PMID- 29365357
TI  - Intraregional model for end-stage liver disease score variation in liver
      transplantation: Disparity in our own backyard.
AB  - Variation in average Model for End-Stage Liver Disease (MELD) score at liver
      transplantation (LT) by United Network for Organ Sharing (UNOS) regions is well
      documented. The present study aimed to investigate MELD variation at the
      interregional, intraregional, and intra-donation service area (DSA) levels.
      Patients undergoing LT between 2015 and 2016 were obtained from the UNOS standard
      analysis and research file. The distribution of allocation MELD score including
      median, skew, and kurtosis was examined for all transplant programs.
      Intraregional median allocation MELD varied significantly within all 11 UNOS
      regions. The largest variation between programs was seen in region 5 (MELD 24.0
      versus 38.5) and region 3 (MELD 20.5 versus 32.0). Regions 1, 5, and 9 had the
      largest proportion of programs with a highly negative skewed MELD score (50%,
      57%, and 57%, respectively), whereas regions 3, 6, 10, and 11 did not have any
      programs with a highly negative skew. MELD score distribution was also examined
      in programs located in the same DSA, where no barriers exist and theoretically no
      significant difference in allocation should be observed. The largest DSA
      variation in median allocation MELD score was seen in NYRT-OP1 LiveOnNY (MELD
      score variation 11), AZOB-OP1 Donor Network of Arizona (MELD score variation 11),
      MAOB-OP1 New England Organ Bank (MELD score variation 9), and TXGC-OP1 LifeGift
      Organ Donation Ctr (MELD score variation 9). In conclusion, the present study
      demonstrates that this MELD disparity is not only present at the interregional
      level but can be seen within regions and even within DSAs between programs
      located as close as several city blocks away. Although organ availability likely
      accounts for a component of this disparity, the present study suggests that
      transplant center behavior may also play a significant role. Liver
      Transplantation 24 488-496 2018 AASLD.

PMID- 29365359
TI  - Mid-Upper Arm Circumference Z-Score as Determinant of Nutrition Status: Does
      Occam's Razor Apply?

PMID- 29365358
TI  - Perioperative loss of psoas muscle is associated with patient survival in living
      donor liver transplantation.
AB  - Patients with end-stage liver disease show sarcopenia, and preoperative
      sarcopenia is independently associated with patient mortality after liver
      transplantation. However, few studies have examined the relationship between
      perioperative loss of core muscle and patient mortality in living donor liver
      transplantation (LDLT). This study was performed to investigate the association
      between a perioperative decrease in the psoas muscle index (PMI) and patient
      mortality after LDLT. Adult patients (age >= 18 years) undergoing LDLT between
      January 2009 and December 2016 were classified into low-loss (>25th quartile)
      versus high-loss (<=25th quartile) groups according to PMI change between the day
      before surgery and postoperative day (POD) 7. Patient survival was compared
      between the 2 groups, and factors affecting survival were analyzed. The median
      (interquartile range) level of PMI change from the day before surgery to POD 7
      was -4.8% (-11.7%-1.2%). Although there was no preoperative difference in PMI
      between the low-loss and high-loss groups, patients with PMI change <=-11.7%
      showed poorer survival than those with PMI change >-11.7% during the follow-up
      period. A PMI decrease <=-11.7% between the day before surgery and POD 7 is an
      independent predictor of patient mortality after LDLT. In addition,
      intraoperative packed red blood cell transfusion, graft fat percentage, and
      reoperation and infection after surgery were significantly associated with
      patient mortality. In conclusion, a PMI decrease <=-11.7% between the day before
      surgery and POD 7 is an independent predictor of patient mortality after LDLT. It
      is necessary to identify the factors responsible for the perioperative decrease
      in skeletal muscle mass and to ascertain if they are modifiable to improve
      patient survival after LDLT. Liver Transplantation 24 623-633 2018 AASLD.

PMID- 29365360
TI  - Drug Shortages: Effect on Parenteral Nutrition Therapy.
AB  - Drug shortages continue to be a threat to the health and welfare of numerous
      patients in the United States. For patients who depend on parenteral nutrition
      (PN) for survival, these shortages pose an even greater threat. Almost 75% of
      active drug shortages are sterile injectables, which includes PN components.
      Providing PN therapy is particularly challenging for clinicians because this is a
      complex medication and may contain 40 or more individual ingredients, of which
      multiple components may simultaneously be in limited supply. The availability of
      PN components must be considered during every step of the PN use process from
      ordering the PN prescription to administering this therapy to a patient.
      Alterations to a standardized process can lead to medication errors that can
      adversely affect patient outcomes and consume healthcare resources.

PMID- 29365361
TI  - Enteral Access Devices: Types, Function, Care, and Challenges.
AB  - Enteral access feeding devices are placed in patients who have a functional and
      accessible gastrointestinal (GI) tract but are not able to consume or absorb
      enough nutrients to sustain adequate nutrition and hydration. For many
      individuals, enteral nutrition support is a lifesaving modality to prevent or
      treat a depleted nutrient state that can lead to tissue breakdown, compromised
      immune function, and poor wound healing. Psychological well-being is also
      affected with malnutrition and dehydration, triggering feelings of apathy,
      depression, fatigue, and loss of morale, negatively impacting a patient's ability
      for self-care. A variety of existing devices can be placed through the nares,
      mouth, stomach or small intestine to provide liquid nutrition, fluids, and
      medications directly to the GI tract. If indicated, some of the larger-bore
      devices may be used for gastric decompression and drainage. These enteral access
      devices need to be cared for properly to avert patient discomfort, mechanical
      device-related complications, and interruptions in the delivery of needed
      nutrients, hydration, and medications. Clinicians who seek knowledge about
      enteral access devices and actively participate in the selection and care of
      these devices will be an invaluable resource to any healthcare team. This article
      will review the types, care, proper positioning, and replacement schedules of the
      various enteral access devices, along with the prevention and troubleshooting of
      potential problems.

PMID- 29365362
TI  - Graduation Day: Healthcare Transition From Pediatric to Adult.
AB  - Because more patients with pediatric-onset chronic conditions are surviving into
      adulthood, they are graduating from pediatric healthcare to self-management and
      adult healthcare. This transfer of care needs to be a process of transitioning
      medical and nutrition care. Despite having position statements from professional
      organizations and several proposed models, issues in the transition process have
      been well described, and gaps in transition care persist. Healthcare providers
      need to be aware of special needs of emerging adults related to education on
      chronic condition and self-management skills, emotional support before and after
      transition, and legal rights for both the patient and the parent if the emerging
      adult is not developmentally appropriate to make his or her own healthcare
      decisions. Both pediatric and adult providers need to be in active communication
      with each other and the patient to develop trusting relationships and actively
      support the transition of care. This review of literature describes several
      models for transitioning, measureable outcomes, insurance provider issues, and
      legal issues pertaining to healthcare transition.

PMID- 29365364
TI  - Determining Efficacy, Safety, and Preparation of Standardized Parenteral
      Nutrition.

PMID- 29365366
TI  - Letter from New Zealand ... and Season's greetings.

PMID- 29365365
TI  - Hepatocyte-induced CD4+ T cell alloresponse is associated with major
      histocompatibility complex class II up-regulation on hepatocytes and suppressible
      by regulatory T cells.
AB  - Hepatocyte transplantation is a promising therapeutic approach for various liver
      diseases. Despite the liver's tolerogenic potential, early immune-mediated loss
      of transplanted cells is observed, and longterm acceptance has not been achieved
      yet. Patients deemed tolerant after liver transplantation presented an increased
      frequency of regulatory T cells (Tregs), which therefore also might enable
      reduction of posttransplant cell loss and enhance longterm allograft acceptance.
      We hence characterized hepatocyte-induced immune reactions and evaluated the
      immunomodulatory potential of Tregs applying mixed lymphocyte cultures and mixed
      lymphocyte hepatocyte cultures. These were set up using peripheral blood
      mononuclear cells and primary human hepatocytes, respectively. Polyclonally
      expanded CD4+ CD25high CD127low Tregs were added to cocultures in single-/trans
      well setups with/without supplementation of anti-interferon gamma (IFNgamma)
      antibodies. Hepatocyte-induced alloresponses were then analyzed by multicolor
      flow cytometry. Measurements indicated that T cell response upon stimulation was
      associated with IFNgamma-induced major histocompatibility complex (MHC) class II
      up-regulation on hepatocytes and mediated by CD4+ T cells. An indirect route of
      antigen presentation could be ruled out by use of fragmented hepatocytes and
      culture supernatants of hepatocytes. Allospecific proliferation was accompanied
      by inflammatory cytokine secretion. CD8+ T cells showed early up-regulation of
      CD69 despite lack of cell proliferation in the course of coculture.
      Supplementation of Tregs effectively abrogated hepatocyte-induced alloresponses
      and was primarily cell contact dependent. In conclusion, human hepatocytes induce
      a CD4+ T cell alloresponse in vitro, which is associated with MHC class II up
      regulation on hepatocytes and is susceptible to suppression by Tregs. Liver
      Transplantation 24 407-419 2018 AASLD.

PMID- 29365368
TI  - Genetic screening and functional analysis of CASP9 mutations in a Chinese cohort
      with neural tube defects.
AB  - AIM: Neural tube defects (NTDs) are birth defects of the nervous system and are
      the second most frequent cause of birth defects worldwide. The etiology of NTDs
      is complicated and involves both genetic and environmental factors. CASP9 is an
      initiator caspase in the intrinsic apoptosis pathway, which in Casp9-/- mice has
      been shown to result in NTDs because of decreased apoptosis. The aim of this
      study was to evaluate the potential genetic contribution of the CASP9 gene in
      human NTDs. METHODS: High-throughput sequencing was performed to screen genetic
      variants of CASP9 genes in 355 NTD cases and 225 matched controls. Apoptosis
      relevant assays were performed on transiently transfected E9 neuroepithelial
      cells or human embryonic kidney 293T cells, to determine the functional
      characteristics of NTD-specific rare variants under complete or low folic acid
      (FA) status. RESULTS: We found significant expression of CASP9 rare variants in
      NTDs and identified 4 NTD-specific missense variants. Functional assays
      demonstrated that a p.Y251C variant attenuates apoptosis by reducing CASP9
      protein expression and decreasing activity of the intrinsic apoptosis pathway.
      From this, we conclude that this variant may represent a loss-of-function
      mutation. A 4-time recurrent p.R191G variant did not affect intrinsic apoptosis
      in complete medium, while it completely inhibited apoptosis induced by low FA
      medium. CONCLUSION: Our findings identify a genetic link for apoptosis in human
      NTDs and highlight the effect of gene-environment interactions in a complex
      disease.

PMID- 29365367
TI  - Vitamin D and respiratory health in the Busselton Healthy Ageing Study.
AB  - BACKGROUND AND OBJECTIVE: The relationship between vitamin D and respiratory
      disease was examined by cross-sectional analysis of a large community-based
      sample. METHODS: Serum 25-hydroxyvitamin D (25OHD) and history of respiratory
      disease, symptoms (recorded by questionnaire) and spirometry were measured in
      5011 adults aged 45-69 years. Adjustments were made for age, sex, season and
      smoking (Model A), plus body mass index (BMI) and physical activity level (Model
      B), plus history of chronic diseases (Model C). RESULTS: Mean (SD) age was 58 (SD
      6) years with 45% males, 10% current smokers and 12% taking vitamin D
      supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three
      models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds
      ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze
      (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with
      vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the
      three models (1.17% higher, compared with the 50-100 nmol/L group in Model C).
      CONCLUSION: Low levels of serum 25OHD were independently associated with asthma,
      bronchitis, wheeze and chest tightness after three levels of adjustment for
      potential confounders. Higher vitamin D levels were associated with higher levels
      of lung function.

PMID- 29365369
TI  - The nutritional care of people living with dementia at home: A scoping review.
AB  - There are an increasing number of people with dementia living in their own home
      for longer, often supported by a family member. The symptoms of dementia can
      affect an individual's nutritional status, which can lead to a reduced quality of
      life for the person with dementia and their family members. A scoping review was
      conducted from July 2016 until September 2016, using a recognised framework, to
      explore what is currently known, and identify any gaps in the research regarding
      the nutritional care of people living with dementia at home. This included any
      interventions that may have been trialled or implemented, and the views of those
      living with dementia, carers and clinicians. Six electronic databases were
      searched from inception to July 2016. A review team was involved in screening and
      data extraction for selected articles. Published qualitative and quantitative
      studies were included that explored the nutritional care of people living with
      dementia at home. Methods included data extraction and conventional content
      analysis. Stakeholders were involved in the development of final categories.
      Following screening, 61 studies reported in 63 articles were included. Most
      studies were cross-sectional (n = 24), cohort (n = 15) or qualitative (n = 9).
      Only three were randomised controlled trials. Three overarching categories
      represented the results: Timely identification of nutritional risk and subsequent
      regular monitoring of nutritional status, multi-component tailored interventions
      and the influence of the care-giving dyad on nutritional status. Many studies
      identify people living at home with dementia as a vulnerable group prone to
      malnutrition; however, a lack of interventions exists to address the increased
      risk. There is a lack of research exploring the role of home care providers and
      healthcare professionals in the provision of nutritional care. Further research
      is required to explore how the emotional aspect of the care-giving dyad
      influences nutritional care.

PMID- 29365370
TI  - Candesartan ameliorates brain inflammation associated with Alzheimer's disease.
AB  - AIMS: Alzheimer's disease (AD) pathology is associated with brain inflammation
      involving microglia and astrocytes. The renin-angiotensin system contributes to
      brain inflammation associated with AD pathology. This study aimed to investigate
      the role of candesartan, an angiotensin II type 1 receptor blocker, in modulation
      of glial functions associated with AD. METHODS: Focusing on the role of
      candesartan in glial inflammation, we evaluated inflammatory mediators' levels,
      secreted by lipopolysaccharide-induced microglia following candesartan treatment.
      Also, short-term intranasal candesartan effects on amyloid burden and microglial
      activation were investigated in 5 familial AD mice. RESULTS: Candesartan showed
      anti-inflammatory effects and shifted microglial activation toward a more
      neuroprotective phenotype. Candesartan decreased the lipopolysaccharide-induced
      nitric oxide synthase and cyclooxygenase-2 expression levels, which was
      accompanied by an induction of arginase-1 expression levels and enhanced Abeta1
      42 uptake by microglia. Moreover, intranasally administered candesartan to AD
      mice model significantly reduced the amyloid burden and microglia activation in
      the hippocampus. CONCLUSIONS: These results thus shed light on the
      neuroprotective role of candesartan in the early stage of AD, which might relate
      to modulation of microglial activation states.

PMID- 29365371
TI  - [Running a high-quality periodical, building a communication platform].

PMID- 29365373
TI  - [Evaluation and treatment of children's laryngeal clefts].
AB  - Objectives: To provide the experience about the diagnostic process and following
      management, and to discuss the outcome and predictors in children with laryngeal
      cleft (LC). Methods: A retrospective case study was conducted at an academic
      children's hospital. Thirty children were diagnosed as laryngeal cleft between
      January 2016 and April 2017.Airway evaluations were performed using both flexible
      and rigid endoscopy, and swallowing evaluations were performed using fiberoptic
      endoscopic examination of swallowing or modified barium swallow. Results: Of 30
      cases, 18 were male and 12 were female, ranging in age from birth to 8 years. Two
      cases were diagnosed as type 0 LC, and they were offered thickened liquid without
      medication. Throughout follow-up, they remained asymptomatic and showed no
      respiratory complications. Nineteen children were diagnosed as type I LC. Six of
      them were significantly improved by anti-reflux therapy and feeding instructions.
      Four children were concomitant with swallowing dysfunction and/or neuromuscular
      disorders, and they were given a tracheotomy and routine management. Another 4
      children were submitted surgical repair when routine treatment failed, and their
      symptoms were relieved. Five children were concomitant with larygomalacia, and
      their symptoms were totally ameliorated by supraglottoplasty. Three children were
      diagnosed as type II LC. Two of them received surgical repair and clinically
      improved, and the rest one was treated by anti-reflux therapy and still under
      follow-up. Three children were diagnosed as type III LC. One of them was
      underwent surgical repair and clinically improved. Two children were
      tracheotomized and treated by anti-reflux therapy. Three cases were diagnosed as
      type IV LC at birth and no one survived. Conclusions: Laryngeal cleft is a rare
      congenital anomaly manifesting with a variety of symptoms, including swallowing
      disorder, aspirations, dyspnea, stridor and hoarseness. Diagnosis and treatment
      of laryngeal clefts is a challenge. The best way to evaluate the LC is FEES by
      laryngeal endoscopy combined with MLB. Cases with type 0-I mostly were
      significantly improved by anti-reflux therapy and feeding instructions. When
      routine treatment failed, surgical repair is needed. All the cases with LC type
      II-III need surgical repair as soon as possible. For type IV cases, early
      diagnosis, appropriate treatment and management help to reduce mortality and
      morbidity.

PMID- 29365372
TI  - [Correlation between the changes of fibrinogen and the treatment effect of all
      frequency sudden deafness].
AB  - Objective: To analyze the correlation between the changes of fibrinogen and the
      treatment effect of all-frequency sudden deafness, and to explore the
      individualized treatment strategy for the use of Batroxobin. Methods: Patients
      with all-frequency sudden deafness who were admitted to Department of
      Otorhinolaryngology, People's Hospital of Peking University, from January 2010 to
      September 2016 were selected. All patients were given standard treatment and
      regular use of Batroxobin. Value of fibrinogen on D1 (before treatment) / D3 / D7
      (+/-1) and D14 (+/-2) were recorded, at the same time, the correlation between
      the changes of fibrinogen and prognosis of all-frequency sudden deafness by the
      audiograms of onset and after-treatment of all patients were analyzed.
      Independent t-test was used to analyze normal distributed measurement data and
      chi square linear trend test was used to analyze the curative effect of different
      fibrinogen groups. Results: A total of 148 patients were included, the outcomes
      were worst when the patient's fibrinogen was below 2 g/L or above 4 g/L before
      treatment, ineffective rate were both 50%. The fibrinogen was lowest when the
      treatment came to the third day. Normally, the patient's prognosis was best when
      this value waved between 0.7 and 0.9 g/L, with a total effective rate between
      73.9% and 83.3%. The fibrinogen value of the 7th day was a good indicator of the
      outcome, and Fib7 value was significant lower in patients of effective group than
      ineffective ones ((1.25+/-0.37)g/L vs (1.38+/-0.35) g/L, t=-0.27, P=0.04).
      Patients found a best recovery when Fib7 was below 1 g/L, and the higher the Fib7
      value, the higher the inefficiency (chi(2)=7.55, P=0.01). Batroxobin showed
      safety during the treatment and found no complications. Conclusion: The change of
      fibrinogen in the process of all-frequency sudden deafness is closely related to
      the curative effect.

PMID- 29365374
TI  - [Clinical application of supraclavicular flap for oncologic reconstruction of
      hypopharynx and upper esophagus].
AB  - Objective: To assess the efficacy of supraclavicular artery island flap (SCAIF)
      for the reconstruction of hypopharynx and upper esophagus. Methods: The SCAIF
      procedure on was used in 10 patients, including 8 with hypopharygeal carcinomas,
      1 with esophageal carcinoma and neck skin invasion and 1 with hypopharyngeal
      leiomyosarcoma, at the Otorhinolaryngology Hospital, the First Affiliated
      Hospital, Sun Yatsen University between December 2015 and June 2017. The sizes of
      the flaps were measured in (4-8) cm*(5-12) cm. Clinical indexes such as
      harvesting time and survival were recorded. Results: Harvesting time for SCAIF
      ranged from 20 to 30 minutes, averaging 26 minutes. Nine flaps survived, one flap
      had partially necrosis. Functional outcomes were excellent and the donor sites
      were direct closed without complications. Conclusions: SCAIF is a versatile,
      reliable, and easily harvested flap, with good cosmetic and functional outcomes
      for reconstructing the defects of hypopharynx and upper esophagus.

PMID- 29365375
TI  - [Assessment of psychological status of inpatients with head and neck cancer
      before surgery].
AB  - Objective: To investigate the prevalence and psychosocial characteristics in
      inpatients with head and neck cancer before surgery. Method: From September 2015
      to December 2016, 237 consecutive inpatients with head and neck cancer who had
      been scheduled for surgery were prospectively enrolled in Department of Head and
      Neck Surgery of Shanxi Provincial Tumor Hospital. Mental health symptoms were
      systematically investigated using three psychological instruments: symptom
      checklist-90 (SCL-90), Zung self-rating anxiety scale (SAS) and Zung self-rating
      depression scale (SDS). SPSS 17.0 software was used to analyze the data. And he
      results of SCL-90, SAS and SDS were compared with the Chinese norm. For all
      statistical analyses, a P value <0.05 was considered statistically significant.
      Result: Of 237 patients, 228 (96.2%) completed all the questionnaire. The scores
      of SCL-90 (1.60+/-0.44), SAS (46.67+/-8.51)and SDS(47.50+/-11.43)in patients with
      head and neck cancer were significantly higher than those of Chinese norm
      (t=3.093, t=17.29, t=4.29 respectively and P=0.003, P=0.001, P=0.001
      respectively). Positive proportion identified by three measure tools are 32.9%,
      35.5% and 36.8% respectively. And 42 patients (18.4%) suffered from both anxiety
      and depression. The SCL-90 scores were significantly higher than those of the
      normal standard population, including dimension of somatization obsessive
      compulsive, anxiety, hostility, phobic-anxiety and psychoticism (t=4.47, 3.04,
      2.87, 2.58, 5.46, 4.15 respectively, all P<0.05). Conclusions: This study offers
      important information regarding psychological status in inpatients with head and
      neck cancer before surgery. Identifying these patients using proper screening
      instrument is of great important clinical implications for the early detection,
      management, and reduction of the distress associated with head and neck cancer.

PMID- 29365376
TI  - [Tumor-secreted vascular endothelial growth factor A increases the pulmonary
      metastasis from nasopharyngeal carcinoma].
AB  - Objective: Vascular endothelial growth factor A (VEGFA) was investigated as the
      key protein which might promote the specific metastasis progress of
      nasopharyngeal carcinoma. Methods: Sixteen specimens of pulmonary metastasis
      carcinoma and counterparts in primary nasopharyngeal carcinoma tissue were
      collected from patients. The expression of VEGFA through immunohistochemistry was
      investigated.VEGFA was knocked down by siRNA in two cell lines of nasopharyngeal
      carcinoma (CNE-1 and 5-8F), MTT and Transwell test were used to explore the role
      of VEGFA in praxiology. Then shRNA was used to cultivate the stable CNE-1 cell
      line with down-regulated-expression of VEGFA. The nude mice models were built
      through tail vein injection of specific nasopharyngeal carcinoma cells, and lungs
      were collected to perform further metastasis analysis. Results: Previous genetic
      studies showed that VEGFA had higher expression in metastasis tissue, and the
      result was validated in the present study using immunohistochemistry. The
      percentage of positive cells was 84.8% in pulmonary metastasis group, 51.5% in
      primary tissue group (t=8.639, P<0.05), average optical density was 0.154 in
      pulmonary metastasis group, 0.061 in primary tissue group (t=18.791, P<0.05). Low
      expression of VEGFA inhibited cell viability of optical density value of CNE-1 in
      siRNA gourp was 0.715, 0.902 in control group (t=7.274, P<0.05); 5-8F in siRNA
      group was 0.715, 0.935 in control group (t=7.751, P<0.05). Number counting
      suppressed migration of CNE-1 in siRNA group was 52 per high-power lens, 124 per
      high-power lens in control group (t=29.380, P<0.05), 5-8F in siRNA group was 65
      per high-power lens, 155 per high-power lens in control group (t=18.181, P<0.05).
      Number counting invasion of CNE-1 in siRNA gourp was 38 per high-power lens, 86
      per high-power lens in control group (t=27.665, P<0.05), 5-8F in siRNA group was
      52 per high-power lens, 116 per high-power lens in control group (t=40.972,
      P<0.05) in vitro. Furthermore, knock-down of VEGFA in nasopharyngeal carcinoma
      reduced the pulmonary metastasis in vivo. Number counting of tumor volumes in
      shRNA group was 2.4, and 11.0 in control group (t=6.143, P<0.05); average optical
      density of immunohistochemistry in shRNA group was 0.033, and 0.176 in control
      group (t=15.734, P<0.05). Conclusions: Results above reveal the overexpression of
      VEGFA in nasopharyngeal carcinoma can facilitate the pulmonary metastasis.
      Targeting VEGFA may provide a new biomarker of clinical study.

PMID- 29365377
TI  - [Identification and analysis of the proteins interacted with Prestin in cochlear
      outer hair cells of guinea pig].
AB  - Objective: To explore the regulation and mechanism of Prestin protein by
      identifying the proteins interacted with Prestin in cochlear outer hair cell(OHC)
      and analyzing their biological function. Methods: Co-immunoprecipitation combined
      mass spectrometry technology was used to isolate and identify the proteins
      interacted with Prestin protein of OHC, bioinformatics was used to construct
      Prestin protein interaction network. The proteins interacted with Prestin in OHC
      of guinea pig were determined by matching primary interaction mass spectrometry
      with protein interaction network, and annotated their functions. Results: The
      results of co-immunoprecipitation combined with mass spectrometry showed that 116
      kinds of credible proteins could interact with Prestin. By constructing Prestin
      protein interaction network, matching the results of mass spectrometry and
      analyzing of sub-cellular localization, eight kinds of proteins were confirmed
      that they interacted with Prestin directly, namely EEF2, HSP90AB1, FN1, FLNA,
      EEF1A1, HSP90B1, ATP5A1, and ERH, respectively, which were mainly involved in the
      synthesis and transportation, transmembrane folding and localization, structural
      stability and signal transduction of Prestin protein. Conclusion: EEF2, HSP90AB1,
      FN1, FLNA, EEF1A1, HSP90B1, ATP5A1 and ERH provide molecular basis for sensory
      amplification function of OHCs by participating in biotransformation,
      transmembrane folding and localization, signal transduction and other biological
      processes of Prestin protein.

PMID- 29365379
TI  - [The role of narrow band imaging for the early diagnosis of nasopharyngeal
      carcinoma].

PMID- 29365378
TI  - [The significance of circulating tumor cells in head and neck squamous cell
      carcinoma: a preliminary study].
AB  - Objective: To investigate the significance of circulating tumor cells (CTC) in
      squamous cell carcinoma of the head and neck (HNSCC). Methods: Twenty-four
      patients with HNSCC treated between October 2016 and July 2017 in our department
      were selected (experimental group), including 23 males and 1 females, aged 47-81
      years. There were 14 cases of squamous cell carcinoma of larynx and 10 cases of
      hypopharynx, including I-II stage (5 cases) and III- IV stage (19 cases). All
      patients were primary and/or relapsed after treatment. Nine healthy volunteers
      were selected as control group. A novel in vivo capture technique (CellCellector
      system) was used to detect CTC. SPSS23.0 was used for statistical analysis.
      Results: The total capture rate of CTC in patients with HNSCC before treatment
      was 70.8% (17/24), with 40% (2/5) for patients at I-II stage, and 78.9% (15/19)
      for patients at III- IV stage, and was 0 in patients of control group. The total
      capture rate of CTC in patients with HNSCC after treatment was 50% (8/16). There
      was no significant correlation between CTC and age, sex, location of tumor or
      lymph node metastasis (P>0.05). CTC was related to tumor staging and tumor
      differentiation (P<0.05). The positive rate of EGFRVIII in CTC was 26.3% (5/19).
      Conclusions: The CellCollector system is a very efficient way of detecting CTC,
      and CTC plays an important role in the occurrence, progression and metastasis of
      HNSCC.

PMID- 29365380
TI  - [Application of endoscope assisted curved laryngoscopy technique in transoral
      laryngopharyngeal minimally invasive surgery].
AB  - Objective: To explore the possibility of endoscope assisted curved laryngoscopy
      technique applied in transoral laryngopharyngeal minimally invasive surgery and
      evaluate the advantages of this technique. Methods: Eight patients with huge
      benign lesions in larynx and pharynx undergoing transoral microsurgery at Peking
      University Third Hospital between February 2016 and February 2017 were enrolled
      in this study.The diagnosis included cyst at the base of tongue in two patients,
      cysts in the epiglottis in two patients, hemangioma in two patients, multiple
      masses of the hypopharynx and amyloidosis in supraglottic area in one patient
      each.The time and exposure during surgery, occurrence rate of complication and
      conditions of following-up were recorded. Results: The mean time of surgery was
      20 min, the exposure was satisfying.There was no obvious complication after
      surgery.No residual or recurrent lesion was observed after 1 to 12 months follow
      up(mean time 4.5 months). Conclusion: The endoscope assisted curved laryngoscopy
      technique has advantages in shortening the time of surgery, improving exposure
      and reducing the rate of complication and recurrence.

PMID- 29365381
TI  - [Application of virtual reality in surgical treatment of complex head and neck
      carcinoma].
AB  - Objective: To investigate the application of virtual reality technology in the
      preoperative evaluation of complex head and neck carcinoma and he value of
      virtual reality technology in surgical treatment of head and neck carcinoma.
      Methods: The image data of eight patients with complex head and neck carcinoma
      treated from December 2016 to May 2017 was acquired. The data were put into
      virtual reality system to built the three-dimensional anatomical model of
      carcinoma and to created the surgical scene. The process of surgery was
      stimulated by recognizing the relationship between tumor and surrounding
      important structures. Finally all patients were treated with surgery. And two
      typical cases were reported. Results: With the help of virtual reality, surgeons
      could adequately assess the condition of carcinoma and the security of operation
      and ensured the safety of operations. Conclusions: Virtual reality can provide
      the surgeons with the sensory experience in virtual surgery scenes and achieve
      the man-computer cooperation and stereoscopic assessment, which will ensure the
      safety of surgery. Virtual reality has a huge impact on guiding the traditional
      surgical procedure of head and neck carcinoma.

PMID- 29365382
TI  - [Efficacy of systemic glucocorticoids combined with inhaled steroid on children
      with acute laryngitis].
AB  - Objective: To evaluate the efficacy of systemic glucocorticoid (steroid) combined
      with high dose inhaled steroid in the treatment of children with acute
      laryngitis. Methods: A total of 78 children with acute laryngitis were randomly
      divided into study group(n=40) and control group(n=38) between November 2016 and
      April 2017. In addition to routine treatment of anti infection and symptomatic
      treatment, Dexamethasone injection(0.3-0.5 mg/kg, 1-3 d, according to the
      patient's condition) was provided to each group. In addition to the treatment
      mentioned above, the study group were assigned to receive 1.0 mg Budesonide
      suspension for inhalation, oxygen-driven atomizing inhalation, every/30 minutes,
      2 times in a row, after that every 12 hours. The improvement of inspiratory
      dyspnea, hoarseness, barking cough and wheezing of both groups was evaluated at
      30 min, 1 h, 2 h, 6 h, 12 h, 24 h and 72 h after treatment.Sigmaplot 11.5
      software was used to analyze the data. Results: No significant difference was
      detected in terms of inspiratory dyspnea, hoarseness, barking cough or stridor
      score before treatment between the two groups(P>0.05). Compared with those before
      treatment, symptoms of inspiratory dyspnea, hoarseness, barking cough and stridor
      score of both groups improved markedly at 12 h and 24 h after treatment(P<0.05).
      While there was no significant difference regarding inspiratory dyspnea,
      hoarseness, barking cough or stridor score at each time point after treatment
      between the two groups(P>0.05). The effective rate was 92.50% and 92.11% in study
      group and control group, respectively, and no significant difference was noted
      (P>0.05). Conclusion: Compared with single systemic glucocorticoid, systemic
      glucocorticoids combined with inhaled steroid possessed similar efficacy in
      treating acute laryngitis and relieving laryngeal obstruction of children.

PMID- 29365383
TI  - [Application of bedside ultrasound in critically ill patients with second
      percutaneous dilational tracheostomy].

PMID- 29365384
TI  - [Spontaneous cervical and mediastinal hematoma from parathyroid adenoma
      hemorrhage: one case report].

PMID- 29365385
TI  - [Reoccurrence of congenital piriform sinus fistula after the internal opening
      obliteration with CO(2) laser cauterization: one case report].

PMID- 29365386
TI  - [A case report of Langerhans cell histiocytosis in sphenoid sinus].

PMID- 29365387
TI  - [Strategy for minimally invasive cochlear implantation and residual hearing
      preservation].
AB  - In the past few decades, considerable development was achieved in the cochlear
      implantation following the emergence of innovative electrode array and advances
      in minimally invasive surgery. Minimally invasive technique led to a better
      preservation of residual low-frequency hearing. The loss of residual hearing was
      caused by complicated factors. According to previous studies, a slower and stable
      speed of electrode insertion and the use of perioperative steroids were
      demonstrated to have a positive impact on hearing preservation. The selection of
      electrode array or its insertion approaches didn't show any distinctive benefits
      in hearing preservation.

PMID- 29365388
TI  - [Neuromuscular properties of genioglossus activity in healthy adults and
      obstructive sleep apnea patients].
AB  - Upper airway patency closely contact with neuromuscular airway regulation during
      respiratory, especially the activity of the pharyngeal dilators. The genioglossus
      is the largest pharyngeal dilators with its contraction playing the most
      important role in keeping the pharyngeal airway open. In healthy individuals,
      genioglossus activation shows a negative correlation with pharyngeal
      collapsibility and upper airway resistance. Negative pressure during inspiration
      can stimulate airway mechanoreceptors to produce a muscle reflex activity.
      However, in obstructive sleep apnea (OSA) patients, the muscles cannot always
      compensate for the increased mechanical load, resulting in frequent obstructive
      breathing events. A number of studies have shown that the collapsibility of upper
      airway during sleep in OSA patients is closely related to the activity of
      genioglossus electromyography(GGEMG). The present article describes the current
      understanding regarding the characters of GGEMG during sleep in healthy adults,
      as well as the pathophysiology of GGEMG in OSA patients.

PMID- 29365389
TI  - [Advances in tracheal transplantation].
AB  - The length of tracheal defect or stenosis exceeded 5 cm could not be treated by
      simple resection and end-to-end anastomosis of the remaining trachea. Various
      ways of tracheal replacement had appeared sequentially, such as radial forearm
      free flap with cartilage grafts, tracheal tissue-engineering and tracheal
      allotransplantation. Among these methods, tracheal allotransplantation displayed
      a better long-term result. In this review, we are focused on recent advances in
      tracheal allotransplantation, particularly on revascularization and
      reepithelialization of graft, as well as on the application of immunosuppressive
      agents.

PMID- 29365391
TI  - [Expert consensus on minimal residual disease detection of acute leukemia and
      plasma cell neoplasms by multi-parameter flow cytometry].

PMID- 29365390
TI  - [Minutes of the Rhinology World Congress 2017].

PMID- 29365392
TI  - [Gene mutations from 511 myelodysplastic syndromes patients performed by targeted
      gene sequencing].
AB  - Objective: To study the characteristics of gene mutations in Chinese
      myelodysplastic syndromes (MDS) patients. Methods: A total of 511 Chinese
      patients with MDS performed 112-gene targeted sequencing were retrospectively
      analyzed. Results: Eighty-three distinct mutant genes were found in 511 patients
      with MDS. Amongst these, the most frequent mutations was associated with
      epigenetics (50%) , followed by spliceosome (37%) , signal transduction (34%) ,
      transcription factors (24%) and cell cycle/apoptosis (17%) . 439 subjects (86%)
      had at least one gene mutation. The mean number of mutations in refractory anemia
      with unilineage dysplasia (RCUD) was 1.25, refractory anemia with multilineage
      dysplasia (RCMD) was 1.73, refractory anemia with ring sideroblasts (RARS) was
      2.79, refractory anemia with excess blasts-1 (RAEB-1) was 2.22, RAEB-2 was 2.34,
      MDS with isolated 5q- was 2.67, MDS, unclassified (MDS-U) was 2.00. U2AF1 mutant
      subjects were more likely to have isolated+8[Q<0.001, OR=4.42 (95% CI 2.23-8.68)
      ]and less likely to have complex karyotypes[Q=0.005, OR=0.22 (95% CI 0.04-0.72)
      ]. According to the number of gene mutations, all subjects were categorized into
      three groups, namely group with 0-1 mutation, with 2 mutations and with three or
      more mutations. There was a significant difference in overall survival (OS) among
      three groups (P=0.041) . Conclusion: About 90% patients with MDS have at least
      one gene mutation. Genes associated with epigenetics and spliceosome are most
      common mutated genes in MDS. The increased numbers of gene mutations accompany
      with disease evolution and associate with poor prognosis.

PMID- 29365394
TI  - [Allogeneic hematopoietic stem cell transplantation for treatment of refractory
      and relapsed acute myeloid leukemia: outcomes and prognostic factors].
AB  - Objective: To evaluate the outcomes and prognostic factors of patients with
      refractory and relapsed acute myeloid leukemia (AML) who received allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) . Methods: The overall
      survival (OS) , disease free survival (DFS) , acute and chronic graft-versus-host
      disease (GVHD) , relapse rate (RR) , transplantation related mortality (TRM) and
      their related risk factors were analyzed retrospectively. Results: All the
      patients (median age 35 years, range 6 to 58) received myeloablative conditioning
      regimens. All patients had successful engraftment, and the median time of
      neutrophils engraftment was 14 days (range 9 to 25) . Of the patients who
      survived more than 100 days, the accumulative incidence of grade II-IV acute GVHD
      and chronic GVHD (cGVHD) were 27.3% (95%CI 18.9%-36.3%) , 33.9% (95%CI 24.6%
      43.5%) , respectively. Meanwhile, the accumulative incidence of extensive cGVHD
      was 9.3% (95%CI 4.5%-16.1%) . The 3-year OS, DFS, RR, and TRM was 45.0% (95%CI
      34.6%-55.4%) , 45.0% (95%CI 34.8%-55.2%) , 36.6% (95%CI 26.9%-46.4%) and 19.7%
      (95%CI 12.4%-28.3%) respectively. Multivariate analysis revealed four independent
      risk factors: non remission status before transplantation[P=0.009, HR=2.21 (95%CI
      1.22-4.04) ], WBC at diagnosis>50*10(9)/L[P=0.024, HR=2.11 (95%CI 1.11-4.02) ],
      donor age>35 years [P=0.031, HR=1.96 (95%CI 1.06-3.60) ]and without
      cGVHD[P=0.008, HR=0.38 (95%CI 0.18-0.78) ]. According to the risk factors before
      transplantation (non remission status, WBC at diagnosis>50*10(9)/L, donor age>35
      years) , we then defined three subgroups with striking different OS at 3 years:
      no adverse factor (75.0%) ; one adverse factor (46.9%) ; two or three adverse
      factors (15.4%) (chi(2)=26.873, P<0.001) . Conclusion: Allo-HSCT is a promising
      and safe choice for patients with refractory and relapsed AML and relapse is the
      major cause of the transplantation failure. Disease status before
      transplantation, donor age, WBC at diagnosis and cGVHD are confirmed as
      prognostic factors for these patients who received allo-HSCT.

PMID- 29365393
TI  - [Efficacy and safety of IA regimen containing different doses of idarubicin in de
      novo acute myeloid leukemia for adult patients].
AB  - Objective: To investigate the efficacy and safety of IA regimen which contains
      idarubicin (IDA) 8 mg/m(2), 10 mg/m(2) or 12 mg/m(2) as induction chemotherapy
      for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total
      of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015
      in the First Affiliated Hospital of Soochow University and other 36 clinical
      blood centers in China were enrolled in the multicenter, single-blind, non
      randomized, clinical controlled study. To compare the response rate of complete
      remission (CR) , adverse events between different dose idarubicin combined with
      cytarabine (100 mg/m(2)) as induction chemotherapy in newly diagnosed patients of
      adult AML. Results: Of 1 207 evaluable AML patients were assigned to this
      analysis of CR rate. The CR rates of IDA 8 mg/m(2) group, IDA 10 mg/m(2) group
      and IDA 12 mg/m(2) group were 73.6% (215/292) , 84.1% (662/787) and 86.7%
      (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone
      marrow, FAB classification and risk stratification, the odds ratios (95% CI) of
      IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 0.49 (0.34-0.70) and 0.36
      (0.18-0.71) , as compared with the IDA 8 mg/m(2) group (P<0.001, P=0.003) . In
      the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9%
      (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly,
      IA regimen with IDA 10 mg/m(2) was the only beneficial factor affecting CR in
      this group after adjusted for age, blast ratio of bone marrow and FAB
      classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group
      was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) .
      However, the odds ratios (95% CI) of IDA 12 mg/m(2) when compared with the IDA 8
      mg/m(2) was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow
      and FAB classification. The median time (days) of neutrophil count less than
      0.5*10(9)/L in IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group
      were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of
      platelet count lower than 20*10(9)/L were 14 (7-17) , 15 (11-20) and 17 (15-21) ,
      respectively (P=0.001) . The incidences of lung infection in the three groups
      were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions: For young adult
      patients (aged 18-60 years) with AML in China, intensifying induction therapy
      with idarubicin 10 mg/m(2) is clinically superior to IDA 8 mg/m(2) and IDA 12
      mg/m(2) in favorable intermediate AML subgroup. However, idarubicin 12 mg/m(2) is
      more suitable to adverse AML subgroup.

PMID- 29365395
TI  - [Clinical significance of serum calcium and albumin in patients with secondary
      hemophagocytic lymphohistiocytosis].
AB  - Objective: To investigate the clinical significance of serum calcium
      concentrations and albumin levels in patients with secondary hemophagocytic
      lymphohistiocytosis (sHLH) . Methods: The clinical and laboratory data of 68
      patients with newly diagnosed sHLH from April 2013 to April 2016, and 20 healthy
      controls were retrospectively analyzed. The patients were classified as the
      clinical remission group and the progression group according to the response
      criteria. To explore the changes of serum calcium concentrations and albumin
      levels in the patients, its correlations with other laboratory indexes and the
      impact on survival. Results: 1The serum calcium concentrations and albumin levels
      in lymphoma-related HLH group and non-tumor HLH group were lower than control
      group (P<0.05) ; The serum calcium concentrations and albumin levels in the
      clinical remission group after treatment was higher than that before treatment
      (P<0.01) , while in the progression group the serum calcium concentrations after
      treatment decreased (P=0.002) , the albumin levels did not changed significantly
      (P=0.086) .2The serum calcium concentrations in newly diagnosed sHLH patients was
      positively correlated with ANC, PLT, HGB (P<0.05) , and negatively with ferritin
      (P<0.05) ; The overall survival (OS) was significantly longer in patients with
      serum calcium concentration>=1.92 mmol/L than that<1.92 mmol/L (266 d vs 95 d,
      P=0.006) . 3The serum albumin levels in newly diagnosed sHLH patients was
      positively correlated with ANC, HGB (P<0.05) , and negatively with ferritin
      (P<0.05) ; The overall survival was longer in patients with serum albumin level
      >= 26.7 g/L than that<26.7 g/L (263 d vs 95 d, P=0.023) . 4The serum calcium
      concentrations in patients before treatment was positively correlated with serum
      albumin levels (P<0.001) , and no significant correlation was found in control
      group (P=0.079) . Conclusion: The serum calcium concentrations and albumin levels
      have clinical significance for disease diagnosis, decision-making therapy and
      treatment outcomes in the patients with sHLH.

PMID- 29365396
TI  - [Ibrutinib inhibits mesenchymal stem cells-mediated drug resistance in diffuse
      large B-cell lymphoma].
AB  - Objective: To explore the mechanism of ibrutinib on drug resistance diffuse large
      B-cell lymphoma (DLBCL) cells. Methods: DLBCL cell line was cultured with
      mesenchymal stem cells (MSC) , and DLBCL cells which migrated and adhered to MSC
      under microscope was counted. The secretion of CXCL12 by MSC were measured by
      ELISA. The expression of CXCR4 on DLBCL cells were measured by flow cytometry,
      HBL-1 cells were transfected with a CXCR4-lentivector. An Annexin V-binding assay
      was used to detect the induction of apoptosis. Clonogenic growth of DLBCL cells
      was evaluated on MethoCult media. Ibrutinib was injected into NOD/SCID mice,
      tumor growth was assessed via caliper measurements every 3 days. Results: MSC
      promoted migration and adhesion of DLBCL cells to MSC. Ibrutinib inhibited
      migration and adhesion of DLBCL cells to MSC in a dose-dependent manner (P<0.05)
      . CXCL12 secreted by MSC and CXCR4 expressed on DLBCL cells could induce each
      other, which upgraded the levels of secretion and expression. Ibrutinib could
      inhibit the secretion of CXCL12 (SUDHL10: 660 pg/ml vs 1 400 pg/ml, P=0.004; HBL
      1: 720 pg/ml vs 1 490 pg/ml, P=0.018; DLBCL:850 pg/ml vs 1 450 pg/ml, P=0.004)
      and expression of CXCR4 (P<0.05) . When co-cultured with MSC, the ratio of HBL-1
      cells apoptosis in the group of control, mitoxantrone, ibrutinib,
      mitoxantrone+ibrutinib were respectively 15.1%, 17.5%, 23.5%, 58.7%. After
      transfected with a CXCR4-lentivector and overexpressed CXCR4, the ratios of HBL-1
      cells apoptosis were 14.2%, 16.1%, 22.5%, 38.3% respectively. The ratio of DLBCL
      cells apoptosis induced by mitoxantrone was lower when co-cultured with MSC
      (P<0.05) . But with the addition of ibrutinib, the ratio of apoptosis was
      increaed and it was similar to cultivation without MSC, which suggested ibrutinib
      could inhibit drug-resistance induced by MSC. But after transfected with a CXCR4
      lentivector, the overexpression of CXCR4 was detected and the ratio of apoptosis
      was significantly lower when co-cultured with MSC which demonstrated that
      ibrutinib inhibited drug-resistance by inhibiting the expression of CXCR4. MSC
      enhanced lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. The
      number of colonies of control, MSC, Ibrutinib, MSC+Ibrutinib were 113+/-5, 205+/
      4, 62+/-9, 123+/-3 (2.5*10(3)/well, x+/-s) , respectively. The tumor volume of
      NOD/SCID mice were respectively 6 500, 17 000, 4 000, 10 000 mm(3). Ibrutinib
      inhibited lymphoma clonogenicity in vitro and lymphoma cell growth in vitro.
      Conclusion: Ibrutinib targeted the CXCL12/CXCR4 axis, inhibited the expression of
      CXCR4 and inhibited MSC-mediated drug resistance. Ibrutinib also inhibited
      lymphoma clonogenicity in vitro and lymphoma cell growth in vivo. These results
      provided a scientific rationality for relapsed/refractory DLBCL treatment with
      ibrutinib.

PMID- 29365397
TI  - [Clinical and bacteriological analysis of lymphoid tissue neoplasms patients with
      bacteria bloodstream infections].
AB  - Objective: To investigate the clinical status of lymphoid tissue neoplasms
      patients with bacteria bloodstream infections, bacteriology and drug
      susceptibility results, and provide the basis for rational clinical anti
      infection option. Methods: A retrospectively analysis of clinical data and
      bacterial susceptibility test results of patients with bacteria bloodstream
      infections from September 2010 to December 2014 was conducted. Results: A total
      of 134 cases including 107 patients with bloodstream infections were enrolled. 84
      cases were male, 50 cases were female, the median age was 31 (12-71) years old.
      112 cases were agranulocytosis, and 106 cases were severe agranulocytosis
      (ANC<0.1*10(9)/L) . 27 cases underwent hematopoietic stem cell transplantation,
      100 cases received chemotherapy[33 cases with VD (I) CP+/-L
      (vincristine+daunorubicin/idarubicin + cyclophosphamide + prednison+/
      asparaginasum) induction chemotherapy, 41 cases with intensive chemotherapy of
      Hyper-CVAD/MA or MA (mitoxantrone+cytarabine) , 26 cases with other chemotherapy
      regimens], and 7 cases were infected without chemotherapy. 10 patients discharged
      from hospital owing to treatment abandoning, 120 cases were cured through anti
      infective therapy, 2 patients died of bacteria bloodstream infections, 1 patient
      died of sudden cardiac, and 1 patient died of GVHD after allogenic hematopoietic
      stem cell transplantation. A total of 144 strains were isolated, including 108
      strains (75.0%) of Gram-negative bacteria and 36 strains (25.0%) of Gram-positive
      cocci. The susceptibility of Gram-negative bacteria to the carbapenems was
      98.00%, and the adjustment treatment rate of carbapenems was 3.0%. The
      susceptibility of Gram-negative bacteria to the other antibiotics was 60.30%, and
      the adjustment treatment rate was 90.5%. The susceptibility of Grampositive cocci
      to the carbapenems was 49.3%, and to glycopeptides and linezolid was 100.0%.
      Comparing all patients'empirical use of antimicrobial agents with the drugs
      susceptibility results of blood cultures, 80.1% of the patients'initial drug
      selection was sensitive. Conclusion: The lymphoid neoplasms patients experienced
      bacteria bloodstream infections most often after receiving the chemotherapy
      regimens of treating acute lymphoblastic leukemia. The majority type of bacteria
      was Gram-negative bacteria. Drug susceptibility test showed that susceptibility
      of Gram-negative bacteria to the carbapenems was the highest, and the treatment
      adjustment rate was obviously lower. The susceptibility of Gram-positive cocci to
      glycopeptides and linezolid was high, and which could be applied to the patients
      with Gram-positive cocci sepsis on basis of susceptibility results in general.

PMID- 29365399
TI  - [A case report of acute promyelocytic leukemia transforming into acute myeloid
      leukemia M(4)].

PMID- 29365398
TI  - [Bing-Neel syndrome: 3 cases report and a review of the literature].
AB  - Objective: To evaluate the clinical characteristics, diagnosis criteria,
      treatment and prognosis in patients with Bing-Neel Syndrome (BNS) . Methods: The
      clinical characteristics, lab data, treatment and outcomes of 3 Bing-Neel
      syndrome patients diagnosed at Peking Union Medical College Hospital were
      collected. Results: The clinical presentation was heterogeneous without any
      specific common signs or symptoms. One patient was diagnosed with BNS 42 months
      after diagnosis of Waldenstrom macroglobulinemia (WM) by cerebrospinal fluid
      (CSF) cytology and flow cytometry, but dead of infection during the first course
      of chemotherapy. BNS was the first manifestation of WM in the other 2 cases. They
      were diagnosed by flow cytometry and cytology of CSF. The detection of
      MYD88(L)265P mutation in CSF contributed to diagnosis and to sequential
      monitoring of minimal residual disease. They received systemic chemotherapy of FC
      (fludarabine + cyclophosphamide) +/- rituximab and intrathecal therapy, followed
      by maintenance therapy of chlorambucil or R2 (rituximab + lenalidomide) . They
      were followed 17 and 20 months respectively without progression of disease.
      Conclusion: The diagnosis approach of BNS should be based on a combination of CSF
      cytology, flow cytometry and detection of the MYD88(L265P) mutation. The
      detection of MYD88(L265P) mutation may be useful in the monitoring of minimal
      residual disease.

PMID- 29365400
TI  - [Effects of PSMB5 on proliferation and bortezomib chemo-resistance in human
      myeloma cells and its related molecular mechanisms].
AB  - Objective: To investigate the effects of proteasome beta 5 subunit (PSMB5) on
      proliferation and bortezomib (BTZ) chemo-sensitivity of multiple myeloma (MM) and
      its related molecular mechanisms. Methods: We used two MM cell lines, RPMI 8226
      and BTZ drug-resistant cell line RPMI 8226/BTZ100 (hereinafter referred to as
      BTZ100) , as the research object. PSMB5 was overexpressed or knocked down in two
      myeloma cell lines via lentivirus transfection. CCK8 assay was used to detect the
      impact of PSMB5 on cell viability and bortezomib sensitivity in human myeloma
      cells; Using flow cytometry to test the effects of PSMB5 on apoptosis rate of
      human myeloma cells under the treatment of bortezomib; Apoptosis-related gene
      expression of Bax, Bcl-2, p-Akt and cleaved caspase-3 were detected by Western
      blot. Results: 1PSMB5 overexpression and knockdown were successfully constructed
      in RPMI 8226 and BTZ100 cells. 2PSMB5 expression was positively correlated with
      cell proliferation of RPMI 8226 and BTZ100 cells (P<0.05) . 3The cell viability
      was lower after PSMB5 knockdown in RPMI 8226 cells than control cells under the
      same concentration of BTZ[IC(50) at 24 h: (7.01+/-0.47) and (9.64+/-0.55) nmol/L
      respectively, t=6.289, P=0.003]. The cell viability was higher after PSMB5
      overexpression in RPMI 8226 cells than control cells under the same concentration
      of BTZ[IC(50) at 24 h: (10.99+/-0.58) and (9.51+/-0.37) nmol/L respectively,
      t=3.724, P=0.020) . PSMB5 expression was negatively correlated with the
      sensitivity of RPMI 8226 cells to BTZ. The results of BTZ100 cells were similar.
      4The expression of PSMB5 was negatively correlated with the apoptosis of RPMI
      8226 and BTZ100 under the treatment of BTZ. 5Meanwhile, PSMB5 knockdown could
      increase the expression of pro-apoptosis gene Bax and cleaved caspase-3 and
      decrease the expression of anti-apoptotic gene Bcl-2 and p-Akt. PSMB5 over
      expression has the opposite results. Conclusion: PSMB5 knockdown could improve
      the bortezomib sensitivity of MM cells via activation of apoptosis signaling.
      PSMB5 may be a potential therapeutic target for MM.

PMID- 29365401
TI  - [Therapeutic outcomes of CCLG-2008 protocol in the treatment of 424 childhood
      acute lymphoblastic leukemia].

PMID- 29365402
TI  - [Clinical characteristics of four SET-NUP214 positive acute leukemia patients].

PMID- 29365403
TI  - [The clinical value of soluble urokinase plasminogen activation receptor in
      febrile neutropenic patients with hematological malignancies after chemotherapy].

PMID- 29365404
TI  - [Diagnosis and therapeutic outcomes of 12 cases thalassemia with concomitant
      acquired bone marrow failure].

PMID- 29365405
TI  - [Thrombotic microangiopathy with lack of ADAMT13 activity after allogeneic
      hematopoietic stem cell transplantation: a case report and literature review].

PMID- 29365406
TI  - [A monocentric retrospective study of low-dose rituximab in the treatment of 12
      cases refractory or relapsed idiopathic autoimmune hemolytic anemia patients].

PMID- 29365407
TI  - [Efficacy and safety of recombinant human thrombopoietin combined with hormonal
      and cyclosporine in 20 patients with newly diagnosed immune-related
      pancytopenia].

PMID- 29365408
TI  - [Ultrasound detection of children hemophilic arthropathy].

PMID- 29365409
TI  - [Advances in intestinal microbiota and graft versus host disease].

PMID- 29365410
TI  - [Strengthen the cancer surveillance to promote cancer prevention and control in
      China].
AB  - Cancer is a major chronic disease threatening the people's health in China. We
      reviewed the latest advances on cancer surveillance, prevention and control in
      our country, which may provide important clues for future cancer control. We used
      data from the National Central Cancer Registry, to describe and analyze the
      latest cancer statistics in China. We summarized updated informations on cancer
      control policies, conducting network, as well as programs in the country. We
      provided important suggestions on the future strategies of cancer prevention and
      control. The overall cancer burden in China has been increasing during the past
      decades. In 2014, there were about 3 804 000 new cancer cases and 2 296 000
      cancer deaths in China. The age-standardized cancer incidence and mortality rates
      were 190.63/100 000 and 106.98/100 000, respectively. China has formed a
      comprehensive network on cancer prevention and control. Nationwide population
      based cancer surveillance has been built up. The population coverage of cancer
      surveillance has been expanded, and the data quality has been improved. As the
      aging population is increasing and unhealthy life styles persist in our country,
      there will be an unnegligible cancer burden in China. Based on the comprehensive
      rationale of cancer control and prevention, National Cancer Center of China will
      perform its duty for future precise cancer control and prevention, based on
      cancer surveillance statistics.

PMID- 29365411
TI  - [Report of Cancer Incidence and Mortality in China, 2014].
AB  - Objective: The registration data of local cancer registries in 2014 were
      collected by National Central Cancer Registry (NCCR)in 2017 to estimate the
      cancer incidence and mortality in China. Methods: The data submitted from 449
      registries were checked and evaluated, and the data of 339 registries out of them
      were qualified and selected for the final analysis. Cancer incidence and
      mortality were stratified by area, gender, age group and cancer type, and
      combined with the population data of 2014 to estimate cancer incidence and
      mortality in China. The age composition of standard population of Chinese census
      in 2000 and Segi's population were used for age-standardized incidence and
      mortality in China and worldwide, respectively. Results: Total covered population
      of 339 cancer registries (129 in urban and 210 in rural) in 2014 were 288 243 347
      (144 061 915 in urban and 144 181 432 in rural areas). The mortality verified
      cases (MV%) were 68.01%. Among them, 2.19% cases were identified through death
      certifications only (DCO%), and the mortality to incidence ratio was 0.61. There
      were about 3, 804, 000 new cases diagnosed as malignant cancer and 2, 296, 000
      cases dead in 2014 in the whole country. The incidence rate was 278.07/100, 000
      (males 301.67/100, 000, females 253.29/100, 000) in China, age-standardized
      incidence rates by Chinese standard population (ASIRC) and by world standard
      population were 190.63/100, 000 and 186.53/100, 000, respectively, and the
      cumulative incidence rate (0-74 age years old) was 21.58%. The cancer incidence
      and ASIRC in urban areas were 302.13/100, 000 and 196.58/100, 000, respectively,
      whereas in rural areas, those were 248.94/100, 000 and 182.64/100, 000,
      respectively. The cancer mortality in China was 167.89/100, 000 (207.24/100, 000
      in males and 126.54/100, 000 in females), age-standardized mortality rates by
      Chinese standard population (ASMRC) and by world standard population were
      106.98/100, 000 and 106.09/100, 000, respectively. And the cumulative incidence
      rate (0-74 age years old) was 12.00%. The cancer mortality and ASMRC in urban
      areas were 174.34/100, 000 and 103.49/100, 000, respectively, whereas in rural
      areas, those were 160.07/100, 000 and 111.57/100, 000, respectively. Lung cancer,
      gastric cancer, colorectal cancer, liver cancer, female breast cancer, esophageal
      cancer, thyroid cancer, cervical cancer, encephala and pancreas cancer, were the
      most common cancers in China, accounting for about 77.00% of the new cancer
      cases. Lung cancer, liver cancer, gastric cancer, esophageal cancer, colorectal
      cancer, pancreatic cancer, breast cancer, encephala, leukemia and lymphoma were
      the leading causes of death and accounted for about 83.36% of cancer deaths.
      Conclusions: The progression of cancer registry in China develops rapidly in
      these years, with the coverage of registrations is expanded and the data quality
      was improved steadily year by year. As the basis of cancer prevention and control
      program, cancer registry plays an important role in making the medium and long
      term of anti-cancer strategies in China. As China is still facing the serious
      cancer burden and the cancer patterns varies differently according to the
      locations and genders, effective measures and strategies of cancer prevention and
      control should be implemented based on the practical situation.

PMID- 29365412
TI  - [FAT1 inhibits cell proliferation of esophageal squamous cell carcinoma through
      regulating the expression of CDK4/CDK6/CCND1 complex].
AB  - Objective: To explore the expression of FAT1 in esophageal squamous cell
      carcinoma (ESCC) tissues, and its effect on cell proliferation. Methods: The
      expression levels of FAT1 protein in human ESCC tissues and matched adjacent
      normal tissues were determined by immunohistochemistry (IHC). Lentivirus based
      knockdown of FAT1 was carried out in YSE2 and Colo680N cell lines and 3-(4, 5
      dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assays was
      performed to examine the effect of FAT1 on the proliferation of these ESCC cells.
      Colony formation assay was used to detect the colony formation ability. Flow
      cytometry was performed to analyze the cell cycle and apoptosis. The expression
      levels of cell cycle markers in FAT1 knock out ESCC cell lines were detected by
      real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)
      and Western blot. Results: The relative expression of FAT1 in ESCC tissues was
      66.97+/-21.53, significantly lower than 78.13+/-16.76 of adjacent normal
      tissues(P<0.05). Knockdown of FAT1 promoted cell proliferation and colony
      formation. In YSE2 cell, the division time in negative control (NC) group was (1
      570+/-51) min, significantly longer than (1 356+/-31) min in shFAT1 group. In
      Colo680N cell, division time in NC group was (1 532+/-53) min, significantly
      longer than (1 290+/-30) min in shFAT1 group (P<0.05). Knockdown of FAT1 promoted
      G1-to S-phase transition and resulted in the upregulation of CDK4/CDK6/CCND1.
      Conclusion: FAT1 inhibits the proliferation and G1-to S-phase transition of ESCC
      cells through regulating the protein expression of CDK4/CDK6/CCND1 complex.

PMID- 29365413
TI  - [Clinical significance of NS1-BP expression in esophageal squamous cell
      carcinoma].
AB  - Objective: To investigate the clinical significance of NS1-BP expression in
      patients with esophageal squamous cell carcinoma (ESCC), and to study the roles
      of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98
      tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as
      study group and control group, and these samples were collected in Sun Yat-Sen
      University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues
      which were collected in Cancer Institute and Hospital of Tianjin Medical
      University were used as validation group. Expression of mucosal NS1-BP was
      detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used
      to analyze the survival rate. Multivariate Cox proportional hazard model was used
      to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or
      knocked down in ESCC cells by transient transfection. Protein levels of c-Myc
      were detected by western blot. Cell viability and apoptosis was analyzed by MTT
      assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down
      regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85
      out of 144 ESCC tissues (59.0%), respectively, showing a statistically
      significant difference (P=0.012). In the study group, three-year disease-free
      survival rate of NS1-BP high expression group (53.2%) was significantly higher
      than that of NS1-BP low expression group (27.6%; P=0.009). In the validation
      group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP
      high and low levels groups, respectively, showing a similar results (P=0.016).
      Importantly, multivariate analyses showed that low expression of NS1-BP was an
      independent predictor for chemoradiotherapy sensitivity and shorter disease-free
      survival time in ESCC patients(P<0.05 for all). Furthermore, overexpressed NS1-BP
      in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and
      promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc
      expression, increased cell proliferation and repressed apoptosis. Conclusions:
      NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell
      proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP
      may be a new therapeutic strategy for ESCC patients.

PMID- 29365414
TI  - [Clinical significance of syndecan-1 and syndecan-2 expression in gallbladder
      squamous cell/adenosquamous carcinoma and adenocarcinoma].
AB  - Objective: To investigate the expression of syndecan-1 and syndecan-2 and their
      clinicopathological significance in patients with gallbladder squamous cell
      (SC)/adenosquamous carcinoma (ASC) and adenocarcinoma (AC). Methods: A total of
      126 patients with SC/ASC (n=46) and AC (n=80) were included in this study. The
      expression levels of syndecan-1 and syndecan-2 were detected by EnvisonTM
      immunohistochemistry assay. The clinical and prognostic significance of syndecan
      1 and syndecan-2 were analyzed. Results: In the 46 SC/ASC samples, syndecan-1 and
      syndecan-2 were positively expressed in 29 (63.0%) and 28 (60.9%) tumor tissues,
      respectively. (Positive expression was defined based on the staining in the
      component of squamous cell carcinoma. That is to say, the tissue which
      adenocarcinoma part was positively stained, but squamous cell carcinoma part was
      negatively stained is also regarded as negative.) In the 80 AC samples, 47
      (58.8%) cases showed syndecan-1 positive expression, and 51 (63.8%) showed
      syndecan-2 positive expression. There was no significant difference in the
      positive rates of syndecan-1 and syndecan-2 between SC/ASC and AC groups (P>0.05
      for all). The levels of syndecan-1 and syndecan-2 were associated with tumor
      size, TNM staging, lymph node metastasis, invasion of adjacent tissue, and
      surgical procedures in SC/ASC patients (P<0.05 for all). However, their
      expression was associated with tumor differentiation, tumor size, TNM staging,
      lymph node metastasis, invasion of adjacent tissue, and surgical procedures in AC
      patients (P<0.05 for all). The Kaplan-Meier survival analysis of SC/ASC and AC
      patients revealed that the average survival time for patients with positive
      syndecan-1 and syndecan-2 expression was significantly shorter than that of those
      with negative expression (P<0.01 for all). Cox multivariate analysis indicated
      that syndecan-1 and syndecan-2 expression were independent unfavorable prognostic
      factors for SC/ASC and AC patients (P<0.05 for all). Conclusion: The syndecan-1
      and syndecan-2 expression are associated with the tumor progression and poor
      prognosis in patients with gallbladder SC/ASC and AC.

PMID- 29365415
TI  - [Evaluation of Consistency in detection of epidermal growth factor receptor gene
      T790M mutation in plasma and tumor specimens of patients with lung
      adenocarcinoma].
AB  - Objective: To evaluate the consistency in detection of T790M mutation of
      epidermal growth factor receptor gene (EGFR) in plasma and tumor samples of
      patients with lung adenocarcinoma. Methods: The tumor tissues or cytological
      specimens of 12 patients with operable lung adenocarcinoma(stage I-IIIA) and 100
      patients with advanced stage IIIB-IV lung adenocarcinoma were collected, among
      which 11 patients showed acquired resistance for gefitinib (11/100). In the same
      period, peripheral blood samples were collected from all patients and 50 healthy
      volunteers. Amplification refractory mutation system (ARMS) was used to detect
      EGFR mutations in tumor specimens. Next Generation Sequencing(NGS) based
      circulating single-molecule amplification and resequencing technology (cSMART)was
      performed to quantitatively detect the EGFR mutations in circulating tumor DNA
      (ctDNA) from plasma specimens. Results: The sensitivity, specificity and
      concordance rate of EGFR T790M mutation between plasma and tissue specimens from
      100 advanced stage patients were 50.0%, 72.9% and 72.0%, respectively. For L858R
      mutation and exon 19 deletion mutations, the above mentioned sensitivity,
      specificity and concordance rate were 91.7%, 100.0%, and 98.0%, as well as 79.2%,
      100.0% and 95.0%, respectively. The L858R mutation and exon 19 deletion mutations
      were not detected in plasma of 50 healthy volunteers, whereasT790M mutation(1.0+/
      0.0 copies) was found in 7 individuals(7/50, 14.0%). Similarly, in 12 resectable
      patients, 4 (4/12, 33.3%) T790M mutations were found in plasma (1.2+/-0.2
      copies), but no L858R mutation and 19 exon deletion mutations. In comparison,
      28.0% of patients with advanced lung adenocarcinoma (28/100)had detectable T790M
      mutation in plasma with copy numbers (34.0+/-22.7 copies). Furthermore, the copy
      numbers of T790M were 268.2+/-119.9 in plasma of 5 cases with acquired gefitinib
      resistance. Conclusions: In patients with advanced stages of lung adenocarcinoma,
      the detection of T790M mutation in plasma and tumor specimens is low. The T790M
      mutation also exists in the plasma of some healthy controls, suggesting that
      T790M mutation participates in EGFR signaling pathway and it might function in
      healthy population.

PMID- 29365416
TI  - [MRI findings and pathological features of occult breast cancer].
AB  - Objective: To investigate the magnetic resonance imaging (MRI) findings and
      clinicopathological features of primary lesions in patients with occult breast
      cancer (OBC). Methods: The imaging reports from the Breast Imaging Reporting and
      Data System in 2013 were retrospectively analyzed to investigate the morphology
      and the time signal intensity curve (TIC) of breast lesions in patients with OBC.
      The clinical and pathological characteristics of these patients were also
      included. Results: A total of 34 patients were enrolled. Among these patients, 24
      patients underwent modified radical mastectomy and 18 of them had primary breast
      carcinoma in pathological sections. MRI detected 17 cases of primary lesions,
      including six masse lesions with a diameter of 0.6-1.2 cm (average 0.9 cm), and
      11 non-mass lesions with four linear distributions, three segmental
      distributions, three focal distributions, and one regions distribution. Five
      patients had TIC typeIprimary lesions, ten had TIC type II primary lesions, and
      two had TIC type III primary lesions. Among all 34 cases, 23 of them had complete
      results of immunohistochemistry: 11 estrogen receptor (ER) positive lesions
      (47.8%), tenprogesterone receptor (PR) positive lesions (43.5%), seven human
      epidermal growth factor receptor 2 (HER-2) positive lesions (30.4%), and 20high
      expression(>14%) of Ki-67 (87.0%). The proportion of type luminal A was 4.3%,
      type luminal B was 43.5%, triple negative breast cancer (TNBC) was 30.4%, and HER
      2 over expression accounted for 21.7%. Conclusions: The primary lesions of OBC
      usually manifested as small mass lesions, or focal, linear or segmental
      distribution of non-mass lesions. The positive rate of ER and PR was low, but the
      positive rate of HER-2 and the proliferation index of Ki-67 was high. Type
      luminal B is the most common molecular subtype.

PMID- 29365417
TI  - [Combined T2-weighted and diffusion-weighted MR imaging for staging of rectal
      cancers].
AB  - Objective: To compare the diagnostic value of T2 weighted imaging (T2WI),
      diffusion-weighted imaging (DWI), and T2WI+ DWI magnetic resonance imaging (MRI)
      for staging of rectal cancers for improving the accuracy of tumor staging.
      Methods: From January 2011 to December 2013, 120 cases of rectal cancers proved
      by colonoscopy without receiving any anti-tumor treatment were enrolled
      retrospectively. The MRI data for these patients were divided into three groups,
      ie., T2WI, DWI and T2WI+ DWI, for evaluating the tumor stages. The results were
      compared with histopathologic findings. The sensitivity and specificity were
      calculated and compared with chi-square test. The nodal staging was predicted by
      using T2WI+ DWI. Results: The accuracy for prediction of tumor staging was 83.3%,
      65.0% and 92.5% for T2WI, DWI, and T2WI+ DWI respectively. The specificity for
      evaluating T1 and T2 stage, and the sensitivity for evaluating T3 by DWI was
      significantly lower than those using T2WI and T2WI+ DWI in rectal cancers. The
      sensitivity for evaluation of T2 by DWI was lower than that using T2WI+ DWI
      (63.0% vs. 88.9%). The sensitivity for evaluation T2 and specificity for T3 by
      T2WI+ DWI was higher than thouse using T2WI only (88.9% vs. 51.9%, 94.0% vs.
      72.0%). The accuracy for prediction of nodal staging by using T2WI+ DWI was 62.1%
      (72/116). Conclusions: T2WI is the key sequence for staging of rectal cancers.
      Although the diagnostic accuracy was not good by using DWI alone, the combination
      of T2WI and DWI can improve the accuracy significantly for tumor staging in
      rectal cancers, whereas the nodal staging was still a hard task for radiologists.

PMID- 29365419
TI  - [Intrahepatic peripheral cholangiocarcinoma misdiagnosised by imaging: a case
      report].

PMID- 29365420
TI  - [Considerations for anti-cancer drug application by single arm trials].
AB  - Single arm trial (SAT) was widely used for new drug application (NDA) of novel
      anti-cancer drugs in recent years. The listing time was greatly shortened by SAT
      while comparing with randomized controlled trials (RCT). Thus, the companies
      intended to get NDA through SAT. To encourage innovation and accelerate the
      developments of anti-cancer agents, we summarize the background and key issues of
      SAT, discuss the conditions of accepting SAT for NDA, and systematically
      elaborate the design and principles of SAT in this review.

PMID- 29365421
TI  - [A case of giant primary liposarcoma of esophagus].

PMID- 29365418
TI  - [The preliminary report of a registration clinical trial of proton and heavy ion
      irradiation].
AB  - Objective: To verify the safety and efficacy of IONTRIS particle therapy system
      (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total
      of 35 patients were enrolled into this trial: 31 males and 4 females with a
      median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and
      neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with
      hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with
      non-metastatic prostate carcinomas. Phantom dose verification was mandatory for
      each field before the start of radiation. Results: Twenty-two patients received
      carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year,
      all patients were alive. Among the 16 patients with head and neck, thoracic, and
      abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response,
      partial response, stable disease, or disease progression, respectively.
      Progression-free survival rate was 93.8% (15/16). Among the 19 patients with
      prostate cancer, biological-recurrence free survival was 100%. Particle therapy
      was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced
      33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%)
      patients developed grade 1 late adverse effects. No significant change in ECOG or
      body weight was observed. Conclusions: IONTRIS is safe and effective for clinical
      use. However, long term follow-up is needed to observe the late toxicity and long
      term result.

PMID- 29365422
TI  - [Consensus on clinical diagnosis, treatment and pedigree management of hereditary
      colorectal cancer in China].
AB  - Hereditary colorectal cancer can be divded into two categories based on the
      presence or absence of polyps. The first category is characterized by the
      development of polyposis, which includes familial adenomatous polyposis (FAP);
      The second category is nonpolyposis colorectal cancer, which is represented by
      Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree
      management of hereditary colorectal cancer in China" developed by the Genetics
      Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is
      composed of three sections, including hereditary nonpolyposis syndrome, polyposis
      syndrome as well as genetic evaluation of hereditary colorectal cancer. The
      consensus aims to provide recommendations on management of the respective
      hereditary syndromes in terms of definition, clinical and pathological features,
      diagnostic standards, treatment, and follow-ups. In addition to describing
      diagnostic and treatment strategies, prophylactic treatment as well as genetic
      screening and pedigree monitoring is highly recommended. Through the
      establishment of this expert consensus, we hope to promote better understanding
      of hereditary colorectal cancer for clinicians and encourage standardized
      treatment through multidisciplinery approaches, eventually improving clinical
      treatment and pedigree management of hereditary colorectal cancer in China.

PMID- 29366299
TI  - Identification, sequence analysis, and infectivity of H9N2 avian influenza
      viruses isolated from geese.
AB  - The subtype H9N2 avian influenza virus greatly threatens the Chinese poultry
      industry, even with annual vaccination. Waterfowl can be asymptomatically
      infected with the H9N2 virus. In this study, three H9N2 virus strains, designated
      A/Goose/Jiangsu/YZ527/2011 (H9N2, Gs/JS/YZ527/11), A/Goose/Jiangsu/SQ119/2012
      (H9N2, Gs/JS/SQ119/12), and A/Goose/Jiangsu/JD564/2012 (H9N2, Gs/JS/JD564/12),
      were isolated from domestic geese. Molecular characterization of the three
      isolates showed that the Gs/JS/YZ527/11 virus is a double-reassortant virus,
      combining genes of A/Quail/Hong Kong/G1/97 (H9N2, G1/97)-like and
      A/Chicken/Shanghai/F/98 (H9N2, F/98)-like; the Gs/JS/SQ119/12 virus is a triple
      reassortant virus combining genes of G1/97-like, F/98-like, and
      A/Duck/Shantou/163/2004 (H9N2, ST/163/04)-like. The sequences of Gs/JS/JD564/12
      share high homology with those of the F/98 virus, except for the neuraminidase
      gene, whereas the internal genes of Gs/JS/YZ527/11 and Gs/JS/SQ119/12 are closely
      related to those of the H7N9 viruses. An infectivity analysis of the three
      isolates showed that Gs/JS/SQ119/12 and Gs/JS/YZ527/11 replicated well, with
      seroconversion, in geese and chickens, the Gs/JS/JD564/12 did not infect well in
      geese or chickens, and the F/98 virus only infected chickens, with
      seroconversion. Emergence of these new reassortant H9N2 avian influenza viruses
      indicates that these viruses can infect both chicken and goose and can produce
      different types of lesions in each species.

PMID- 29366300
TI  - Analysis of swine leukocyte antigen class I gene profiles and porcine endogenous
      retrovirus viremia level in a transgenic porcine herd inbred for
      xenotransplantation research.
AB  - Molecular characterization of swine leukocyte antigen (SLA) genes is important
      for elucidating the immune responses between swine-donor and human-recipient in
      xenotransplantation. Examination of associations between alleles of SLA class I
      genes, type of pig genetic modification, porcine endogenous retrovirus (PERV)
      viral titer, and PERV subtypes may shed light on the nature of xenograft
      acceptance or rejection and the safety of xenotransplantation. No significant
      difference in PERV gag RNA level between transgenic and non-transgenic pigs was
      noted; likewise, the type of applied transgene had no impact on PERV viremia. SLA
      1 gene profile type may correspond with PERV level in blood and thereby influence
      infectiveness. Screening of pigs should provide selection of animals with low
      PERV expression and exclusion of specimens with PERV-C in the genome due to
      possible recombination between A and C subtypes, which may lead to autoinfection.
      Presence of PERV-C integrated in the genome was detected in 31.25% of specimens,
      but statistically significant increased viremia in specimens with PERV-C was not
      observed. There is a need for multidirectional molecular characterization (SLA
      typing, viremia estimation, and PERV subtype screening) of animals intended for
      xenotransplantation research in the interest of xeno-recipient safety.

PMID- 29366301
TI  - Marek's disease vaccine activates chicken macrophages.
AB  - To provide insights into the role of innate immune responses in vaccine-mediated
      protection, we investigated the effect of Marek's disease (MD) vaccine,
      CVI988/Rispens, on the expression patterns of selected genes associated with
      activation of macrophages in MD-resistant and MD-susceptible chicken lines.
      Upregulation of interferon gamma, interleukin (IL)-1beta, IL-8, and IL-12 at
      different days post-inoculation (dpi) revealed activation of macrophages in both
      chicken lines. A strong immune response was induced in cecal tonsils of the
      susceptible line at 5 dpi. The highest transcriptional activities were observed
      in spleen tissues of the resistant line at 3 dpi. No increase in the population
      of CD3+ T cells was observed in duodenum of vaccinated birds at 5 dpi indicating
      a lack of involvement of the adaptive immune system in the transcriptional
      profiling of the tested genes. There was, however, an increase in the number of
      macrophages in the duodenum of vaccinated birds. The CVI988/Rispens antigen was
      detected in the duodenum and cecal tonsils of the susceptible line at 5 dpi but
      not in the resistant line. This study sheds light on the role of macrophages in
      vaccine-mediated protection against MD and on the possible development of new
      recombinant vaccines with enhanced innate immune system activation properties.

PMID- 29366302
TI  - Effect of immunization routes and protective efficacy of Brucella antigens
      delivered via Salmonella vector vaccine.
AB  - An anti-Brucella vaccine candidate comprised of purified Brucella
      lipopolysaccharide (LPS) and a cocktail of four Salmonella Typhimurium (ST)
      Brucella vectors was reported previously. Each vector constitutively expressed
      highly conserved Brucella antigens (rB), viz., lumazine synthase (BLS), proline
      racemase subunit A, outer membrane protein-19 (Omp19), and Cu-Zn superoxide
      dismutase (SOD). The present study determined a relative level of protection
      conferred by each single strain. Upon virulent challenge, the challenge strain
      was recovered most abundantly in non-immunized control mice, with the ST-Omp19-,
      ST-BLS-, LPS-, and ST-SOD-immunized mice showing much less burden. Indirect
      enzyme-linked immunosorbent assay-based assay also confirmed the induction of
      antigen-specific immunoglobulin G for each antigen delivered. In a route-wise
      comparison of the combined vaccine candidate, intraperitoneal (IP), intramuscular
      (IM), and subcutaneous immunizations revealed an indication of highly efficient
      routes of protection. Splenocytes of mice immunized via IM and IP routes showed
      significant relative expression of IL-17 upon antigenic pulsing. Taken together,
      each of the Brucella antigens delivered by ST successfully induced an antigen
      specific immune response, and it was also evident that an individual antigen
      strain can confer a considerable degree of protection. More effective protection
      was observed when the candidate was inoculated via IP and IM routes.

PMID- 29366304
TI  - Factors Affecting the Result of Intralesional Corticosteroid Injection in
      Patients With Oral Lichen Planus.
AB  - OBJECTIVES: To examine the factors which affect the improvement or the recurrence
      of disease after intralesional steroid injection in patients with oral lichen
      planus (OLP). METHODS: Sixty-two patients diagnosed as OLP were treated with
      intralesion corticosteroid injection. To evaluate the objective severity of OLP,
      total severity score of OLP was assessed. To examine the factors affecting the
      therapeutic effect of intralesional steroid injection, factors were compared
      between the symptom-improved group and symptom-not-improved group. To assess the
      symptom of patients, patients filled in 10-cm visual analogue scale, along with
      an Oral Health Impact Profile-14. RESULTS: Symptoms improved in 50 patients
      (80.6%, symptom-improved group), but not in 12 patients (symptom-not-improved
      group). In a comparison between both group, OLP with lip involvement was the only
      variable which showed significant difference (P=0.008). Twenty-nine of 50
      patients had recurrence of OLP (58%, recurrence group) and 21 of 50 patients did
      not have recurrence (42%, no-recurrence group). Statistically significant
      differences were not found between both groups. CONCLUSION: This study suggested
      that patients suffering from OLP with lesion on the lip might not be effective in
      treating with intralesional corticosteroid injection.

PMID- 29366305
TI  - Primary Cutaneous Mucinous Carcinoma with Extramammary Paget's Disease: Eccrine
      or Apocrine?
AB  - Primary cutaneous mucinous carcinoma (PCMC) is an uncommon tumor of the sweat
      gland origin. The occurrence of PCMC is mostly in middle-aged and older patients,
      with a slight male predominance. Most cases of PCMC arise on the head, with a
      preference for eyelids. The histogenesis of PCMC, whether eccrine or apocrine,
      remains controversial. We report a rare case of PCMC with secondary extramammary
      Paget's disease in the groin of a 75-year-old man, which favored an apocrine
      origin. Furthermore, based on a review of the literature, we provide several
      histologic clues that can be used to differentiate PCMC from metastatic mucinous
      carcinoma.

PMID- 29366303
TI  - Association between endotoxin levels in dust from indoor swine housing
      environments and the immune responses of pigs.
AB  - Indoor animal husbandry environments are inevitably contaminated with endotoxins.
      Endotoxin exposure is associated with various inflammatory illnesses in animals.
      This cross-sectional study evaluated the relationship between the degree of
      endotoxin exposure and the cellular and humoral immune profiles of fattening
      pigs. Blood samples were taken from the jugular vein of 47 pigs from ten pig
      farms in Korea. Whole blood cell counts and plasma immunoglobulin (Ig) classes
      were determined. Peripheral-blood mononuclear cells were stimulated in vitro with
      concanavalin A for 48 h, and cytokines released into culture supernatants were
      measured. The barns in which the pigs lived were assessed for endotoxin levels in
      the total and respirable dust by using the limulus amebocyte lysate kinetic QCL
      method. Low and high endotoxin exposures were defined as <= 30 and > 30 EU/m3,
      respectively. Compared to pigs with low endotoxin exposure (n = 19), highly
      exposed pigs (n = 28) had higher circulating neutrophil and lymphocyte
      (particularly B cells) counts, IgG and IgE levels, interferon-gamma (IFNgamma)
      and interleukin (IL)-4 productions, and lower IgA levels and tumor necrosis
      factor-alpha (TNFalpha) production. The IL-4, IFNgamma, and TNFalpha levels
      significantly correlated with endotoxin level and/or pig age. Constant exposure
      of pigs to high levels of airborne endotoxins can lead to aberrant immune
      profiles.

PMID- 29366306
TI  - Video-assisted anal fistula treatment in the management of complex anal fistula:
      a single-center experience.
AB  - BACKGROUND: Video-assisted anal fistula treatment (VAAFT) is now a mature
      technique, supported by many short-term published case series. METHODS: We
      designed a monocentric, retrospective and observational study in order to
      evaluate early and long-term outcomes of VAAFT in the treatment of primary and
      recurrent complex anal fistula. Between November 2011 and March 2014, 224
      consecutive patients affected by complex perianal fistula underwent Video
      Assisted Anal Fistula Treatment. Fifty-two were affected by primary and 172 by
      recurrent disease. We registered all intra and postoperative complications and
      healing rate. Median follow-up was 48 months (range 27-60 months). RESULTS: In
      the primary fistula group, 40 of the 52 patients were completely healed within 3
      months after surgery (77%); at 12 months, considering also 12 patients (23%)
      treated with a second VAAFT due to recurrent disease, the overall healing rate
      was 92.3% In the second group with recurrent anal fistula (N.=172), primary
      healing was observed in 110 patients (64%; P=0.1) within 3 months after surgery
      and increases to 80.2%, after 12 months (P=0.06). Few patients required
      analgesics in the postoperative period (N.=33, 14.7%), the remaining did not
      require pain killers at all. All patients were able to resume daily activities
      within 7 days from surgery (range 2-12 days). Main limitation of our study was
      its retrospective and monocentric design. CONCLUSIONS: VAAFT seems to be a safe
      and effective technique for treating primary and recurrent perianal fistula,
      providing a very good healing rate without sphincters impairment and allowing a
      very quick return to normal activities.

PMID- 29366307
TI  - Study on the effect of perfusion weighted imaging on guiding the operation
      implementation for non-enhanced glioma.
AB  - BACKGROUND: The objective of the present study was to observe and analyze the
      significance of perfusion weighted imaging for guiding the operation
      implementation for non-enhanced glioma, and analyze the estimation of the
      histopathological grade of the non-enhanced glioma and the accuracy of the degree
      of malignancy degree before surgery. METHODS: Fifty-six patients diagnosed with
      non-enhanced glioma through conventional magnetic resonance scanning were
      selected. Before surgery, conventional magnetic resonance scanning and perfusion
      weighted imaging were performed on all patients. The property classification was
      performed with the perfusion weighted imaging parameters: cerebral blood volume
      (CBV) and cerebral blood flow (CBF) before surgery. Surgery was performed on the
      56 patients. Tumors were excised and processed for histopathological
      classification and semi-quantitative immunohistochemical analysis of vascular
      endothelial growth factor (VEGF) levels. Histology was compared after surgery and
      the classification accuracy rate was analyzed before surgery. Additionally,
      conventional magnetic resonance scanning and perfusion weighted imaging were
      performed on 15 patients during surgery. RESULTS: We compared and analyzed the
      reference value of perfusion weighted imaging before and during surgery. Residual
      diseased tissues were excised; histopathological examination was performed, and
      semi-quantitative immunohistochemical analysis of VEGF was performed. Regarding
      maximal magnetic resonance perfusion weighted imaging measured before surgery,
      the cerebral blood volume (rCBV), cerebral blood flow (rCBF), and expression
      level of VEGF were positively correlated with the pathological grade of tumors.
      If the rCBV and rCBF values of the non-enhanced glioma were higher, the grade of
      malignancy was higher (P<0.01), and the positive expression rate of VEGF was
      higher (P<0.01). CONCLUSIONS: Magnetic resonance perfusion weighted imaging can
      display vessel growth and distribution within non-enhanced gliomas before
      surgery, and effectively evaluate the histopathological grade and grade of
      malignancy, and provide accurate guidance for tumor resection during surgery.

PMID- 29366308
TI  - Extended right hepatectomy with inferior vena cava replacement for threatening
      venous outflow occlusion in a pretreated undifferentiated pleomorphic sarcoma of
      the liver.

PMID- 29366309
TI  - Treatment of lung adenocarcinoma with second primary small intestinal sarcomatoid
      carcinoma using bevacizumab.

PMID- 29366310
TI  - Effects of long-acting GnRH: a prolonged protocol in assisted pregnancy via IVF
      ET in infertile patients with PCOS.

PMID- 29366311
TI  - Acute diverticulitis and surgical treatment.
AB  - Diverticulitis is a common condition in industrialized countries and an important
      cause of hospital admissions. Its growing trend is a challenge for the surgeons
      who perform emergency surgery, because approximately 15-25% of the patients will
      require surgery, being the surgical management of complicated acute
      diverticulitis controversial. The past decade has seen a paradigm shift in the
      treatment of sigmoid diverticulitis based on new epidemiological studies and
      refinement of surgical techniques that has produced a reassessment of our
      guidelines. CT imaging and sepsis scores allows to stratify the patients and
      better define the therapeutic strategies in each case. Special considerations
      must also be made for patients with a high surgical risk, such as
      immunosuppressed ones. The recommendations to perform surgery after two episodes
      of uncomplicated diverticulitis have been re-evaluated and the belief that new
      episodes may be complicated and associated with high morbidity and mortality has
      been rejected, since the clinical manifestations of this disease are usually
      defined by the first attack. In complicated cases, more patients can be treated
      with resection and primary anastomosis with or without an associated stoma, whose
      reversal rate is much higher than that of a Hartmann's procedure. Likewise,
      laparoscopic surgery performing a peritoneal lavage and drainage without
      associated resection may have an increasing role in the management of these
      patients, although with controversial results, having become laparoscopic colon
      resection the approach of choice for the treatment of this pathology in elective
      settings.

PMID- 29366312
TI  - The role of laparoscopic distal pancreatectomy in elderly patients.
AB  - INTRODUCTION: Minimally invasive surgery has gained wide acceptance in many
      institutions. Complex surgery such as pancreatic resections delayed its diffusion
      due to high rate postoperative complications and technical aspects, while for
      pancreaticoduodenctomy the role of a minimally invasive approach is still on
      debate. Laparoscopic distal pancreatectomy may be considered a safe procedure and
      a valid alternative in selected cases. The operating time, learning curve and the
      costs represent major drawbacks for the laparoscopic approach. Elderly patients
      (>70 years of age) are generally considered to be at higher risk for developing
      complications after pancreatic surgery due to compromised physiological reserve
      and presence of multiple comorbidities. Our aim was to make a review about the
      role of laparoscopic distal pancreatectomy (LDP) in the elderly population.
      EVIDENCE ACQUISITION: A systematic search of the scientific literature was
      performed using PubMed, EMBASE, online journals, and the Internet for all
      publications on LDP and open distal pancreatectomy (ODP) in old age patients. All
      selected articles were reviewed and analyzed. We found 393 abstract that were
      reviewed. We considered all type of publications. EVIDENCE SYNTHESIS:
      Laparoscopic pancreatic resections are considered more difficult due to the
      retroperitoneal organ location and by the presence of surrounding large vessels
      and other crucial structures. Therefore, an adequate learning curve is needed.
      Beyond these remarks, in many institutions, LDP is a standard approach in
      patients with lesions in the body and tail of the pancreas. The most evident
      advantage of LDP is the shorter length of stay. Age alone should not be
      considered as an absolute contraindication for LDP. Obviously, it is still too
      early to assess oncological outcomes, but the R0 resection rate, the number of
      harvested lymph nodes, and the overall survival rate are superimposable to ODP.
      CONCLUSIONS: LDP is safe and feasible if compared to ODP in selected elderly
      patients with body and tail pancreatic tumors. Less blood loss and shorter
      hospital stay are the most evident advantages of minimally invasive approach.
      Randomized controlled trials and high-volume centers prospective studies with
      long-term outcomes are necessary to consider laparoscopy a standard of care.
      Minimally invasive robotic surgery may represent an interesting alternative to
      laparoscopy especially for spleen-preserving procedures.

PMID- 29366313
TI  - Laparoscopic repair of perforated peptic ulcer.
AB  - INTRODUCTION: Perforations of the peptic ulcers (PPUs) are the most common cause
      of emergency surgery among the complications of the gastroduodenal ulcers and the
      leading cause for morbidity and mortality due to secondary peritonitis and
      sepsis. PPU is a condition in which laparoscopic perforation repair (LPR) is an
      optimal solution. It makes possible the identification of the perforation's site
      and allows closure of the perforation and the subsequent peritoneal lavage, as in
      an open repair (OR) but without the large upper mid-abdominal incision. The main
      objective of this review was to evaluate the latest reported results in the
      laparoscopic treatment of the PPU. EVIDENCE ACQUISITION: Using PubMed and EMBASE
      databases between 1989 and June 2017 we did an extensive electronic literature
      search. The search terms used were "laparoscopic perforated peptic ulcer."
      Inclusion criteria were all the published studies that reported the outcomes of
      LPR and LPR compared with OR for PPU were included in the analysis. The exclusion
      criteria included animal or laboratory studies, pediatric surgery trials, papers
      reporting less than 30 cases of LPR, clinical trials without major outcomes, and
      other language then English. EVIDENCE SYNTHESIS: There were 32 studies included,
      counting 3488 patients with LPR and 5208 with OR. OR patients had more frequent
      shock at admission and had a higher ASA risk class. LPR patients had shorter
      hospital stays with two days, morbidity (11.12% vs. 14.71% OR) and mortality
      (1.95% vs. 8.35% OR) were lower. Leakage was three times higher in LPR arm (2.18%
      vs. 0.79% OR). Conversion occurred in 4.18% overall. The three primary reasons
      for conversions were the size of the perforation, the inability to locate the
      perforation and technical difficulties. CONCLUSIONS: LPR showed similar or better
      results than OR in terms of morbidity, mortality, operation time and hospital
      stay, caution is needed as the OR patients tend to be more shocked or with higher
      ASA at presentation. The higher leakage rate after LPR should be addressed in the
      training of the laparoscopic surgeons or other safety measures should be
      developed and employed.

PMID- 29366315
TI  - Radiotherapy and breast reconstruction.
AB  - Indications for post mastectomy radiotherapy are widening to a larger group of
      mastectomy patients and breast reconstruction rates following mastectomy are
      rising all over the world, this leading breast surgeons to face breast
      reconstruction in a growing number of patients who will undergo radiotherapy.
      Increased morbidity is associated with all forms of breast reconstruction in the
      setting of postmastectomy radiotherapy and in patients who previously underwent
      chest wall radiotherapy. Different attitudes towards breast reconstruction in the
      radiotherapy setting are presented in literature. The level of evidence and
      quality of studies investigating breast reconstruction in the setting of PMRT and
      in patients who previously underwent chest wall radiotherapy are low. The
      reconstructive option in the radiotherapy setting must be tailored on the single
      patient according with patients' characteristics and wishes, always considering
      that the best reconstructive timing must be driven by the best oncological
      timing.

PMID- 29366314
TI  - Laparoscopic or open distal pancreatectomy for benign and malignant lesions of
      the pancreas?
AB  - Minimally-invasive techniques were adopted relatively late for pancreatic
      procedures due to their complexity. Today, minimally-invasive distal
      pancreatectomy is the procedure of choice for the treatment of benign or
      premalignant pancreatic lesions due to the advantages inherent to laparoscopy.
      Data on the efficacy of minimally-invasive distal pancreatectomy in oncologic
      surgery is still limited and larger prospective series are needed prior to its
      widespread use for the treatment of pancreatic cancer. This review addresses
      various aspects of distal pancreatectomy, with emphasis on recent developments
      and open controversies.

PMID- 29366316
TI  - Hybrid breast reconstruction.
AB  - We present a new reconstructive system encompassing prostheses and fat grafting
      as integrated tools to improve the final reconstructive outcome. Fat grafting in
      our view is a preoperatively planned part of the reconstruction. The final volume
      we achieve will be made up of fat and implants in a variable percentage according
      to patient's body contour and breast morphology. We used the hybrid breast
      reconstruction technique in more than 350 reconstructions, both immediate and
      delayed, two-stage and DTI, without experiencing higher loco-regional recurrence
      and complication rates when compared with conventional two-stage reconstructions,
      obtaining excellent aesthetic results and high patients' satisfaction levels.

PMID- 29366317
TI  - The argument for peroral endoscopic myotomy in treatment of achalasia.
AB  - Although there has been debate regarding the optimal procedure to palliate
      dysphagia in patients with achalasia, emerging reports of longer term follow-up
      of patients after peroral endoscopic myotomy (POEM) suggest that the POEM
      procedure is efficacious in relief of dysphagia, and that there is infrequent
      need for subsequent procedures for treatment of failure or reflux. The number of
      centers in the United States of America performing POEM for esophageal achalasia
      continues to increase. This report assess the current knowledge of technical
      issues of POEM, outcomes after POEM and the status of POEM centers in the U.S.A.,
      and presents the argument for surgeons to participate in the practice of POEM.

PMID- 29366318
TI  - Gellan Nanohydrogels: Novel Nanodelivery Systems for Cutaneous Administration of
      Piroxicam.
AB  - The feasibility to use gellan nanohydrogels (Ge-NHs) as delivery system for the
      cutaneous administration of piroxicam (PRX) was investigated using gellan
      conjugated with cholesterol or riboflavin. The in vitro skin penetration studies
      through human epidermis were performed using a saturated aqueous drug solution, a
      50% w/v Transcutol aqueous solution, and a commercially available PRX plaster as
      controls. Confocal microscopy, ATR-FTIR spectroscopy, circular dichroism, and a
      dynamometer assisted extrusion assay were performed to clarify the permeation
      mechanism of Ge-NHs. The skin permeation studies evidenced that Ge-NHs enhance
      the PRX retention in the epidermis and, at the same time, slow down the
      permeation process with respect to the controls. NHs can penetrate the stratum
      corneum, and then gradually disassemble thus diffusing in the viable epidermis
      reaching the spinosum layer. In conclusion, NHs represent a novel strategy to
      target poorly permeable compounds in the epidermis, thus improving the management
      of cutaneous pathologies.

PMID- 29366319
TI  - Molecular Toolkit for Gene Expression Control and Genome Modification in
      Rhodococcus opacus PD630.
AB  - Rhodococcus opacus PD630 is a non-model Gram-positive bacterium that possesses
      desirable traits for lignocellulosic biomass conversion. In particular, it has a
      relatively rapid growth rate, exhibits genetic tractability, produces high
      quantities of lipids, and can tolerate and consume toxic lignin-derived aromatic
      compounds. Despite these unique, industrially relevant characteristics, R. opacus
      has been underutilized because of a lack of reliable genetic parts and
      engineering tools. In this work, we developed a molecular toolbox for reliable
      gene expression control and genome modification in R. opacus. To facilitate
      predictable gene expression, a constitutive promoter library spanning ~45-fold in
      output was constructed. To improve the characterization of available plasmids,
      the copy numbers of four heterologous and nine endogenous plasmids were
      determined using quantitative PCR. The molecular toolbox was further expanded by
      screening a previously unreported antibiotic resistance marker (HygR) and
      constructing a curable plasmid backbone for temporary gene expression (pB264).
      Furthermore, a system for genome modification was devised, and three neutral
      integration sites were identified using a novel combination of transcriptomic
      data, genomic architecture, and growth rate analysis. Finally, the first reported
      system for targeted, tunable gene repression in Rhodococcus was developed by
      utilizing CRISPR interference (CRISPRi). Overall, this work greatly expands the
      ability to manipulate and engineer R. opacus, making it a viable new chassis for
      bioproduction from renewable feedstocks.

PMID- 29366320
TI  - Cyclodextrin-Functionalized Fiber Yarns Spun from Deep Eutectic Cellulose
      Solutions for Nonspecific Hormone Capture in Aqueous Matrices.
AB  - A wood based yarn platform for capturing pharmaceutical molecules from water was
      developed. Cellulose fiber yarns were modified with cyclodextrins, and the
      capture of 17alpha-ethinyl estradiol (EE2), a synthetic estrogen hormone used as
      contraceptive, from water was tested. The yarns were prepared by spinning a deep
      eutectic solution (DES) of cellulose in choline chloride-urea. Despite their high
      porosity and water sorption capacity (5 g/g), the spun fiber yarns displayed high
      wet strength, up to 60% of that recorded in dry condition (128 MPa with 17%
      strain at break). Cyclodextrin irreversible attachment on the yarns was achieved
      with adsorbed chitosan and the conjugation reactions and capture of EE2 by the
      cyclodextrin-modified cellulose were confirmed via online detection with Surface
      Plasmon Resonance (SPR). The facile synthesis of the bioactive yarns and EE2
      binding capacity from aqueous matrices (as high as 2.5 mg/g) indicate excellent
      prospects for inexpensive platforms in disposable affinity filtration. The study
      presents a strategy to produce a wood fiber based yarn to be used as a platform
      for human and veterinary pharmaceutical hormone capture.

PMID- 29366322
TI  - Characterizing Sorption and Permeation Properties of Membrane Filters Used for
      Aquatic Integrative Passive Samplers.
AB  - Aquatic integrative passive sampling is a promising approach to measure the time
      weighted average concentration, yet our understanding for the sampling mechanisms
      of polar organic contaminants should be further advanced to fully exploit the
      potential of the method for real-world applications. This study aimed to
      characterize the sorption and permeation properties of poly(ether sulfone) (PES)
      and poly(tetrafluoroethylene) (PTFE) membrane filters (MFs) used for passive
      samplers. Batch sorption experiments with 14 probe chemicals showed that the
      sorption by PES was generally strong, with the respective sorption coefficients
      greater than the octanol-water partition coefficients by 2-3 log units. In
      contrast, the PTFE filter exhibited no significant sorption for all tested
      chemicals, representing a promising candidate MF that avoids lag-times and slow
      responses to fluctuating concentrations. Permeation experiments in a glass cell
      system and successive modeling demonstrated that, if no sorption to the MF
      occurs, the MF permeation of a chemical can be fully described with a first-order
      model that considers the transfer through the aqueous boundary layers and the
      diffusion in water-filled MF pores. Significant sorption to the MF coincided with
      substantial delay of permeation, which was successfully modeled with the local
      sorption equilibrium assumption. These findings have implications for improved
      sampler configurations and successful models for the chemical uptake.

PMID- 29366321
TI  - Ratiometric Gas Reporting: A Nondisruptive Approach To Monitor Gene Expression in
      Soils.
AB  - Fluorescent proteins are ubiquitous tools that are used to monitor the dynamic
      functions of natural and synthetic genetic circuits. However, these visual
      reporters can only be used in transparent settings, a limitation that complicates
      nondisruptive measurements of gene expression within many matrices, such as soils
      and sediments. We describe a new ratiometric gas reporting method for
      nondisruptively monitoring gene expression within hard-to-image environmental
      matrices. With this approach, C2H4 is continuously synthesized by ethylene
      forming enzyme to provide information on viable cell number, and CH3Br is
      conditionally synthesized by placing a methyl halide transferase gene under the
      control of a conditional promoter. We show that ratiometric gas reporting enables
      the creation of Escherichia coli biosensors that report on acylhomoserine lactone
      (AHL) autoinducers used for quorum sensing by Gram-negative bacteria. Using these
      biosensors, we find that an agricultural soil decreases the bioavailable
      concentration of a long-chain AHL up to 100-fold. We also demonstrate that these
      biosensors can be used in soil to nondisruptively monitor AHLs synthesized by
      Rhizobium leguminosarum and degraded by Bacillus thuringiensis. Finally, we show
      that this new reporting approach can be used in Shewanella oneidensis, a
      bacterium that lives in sediments.

PMID- 29366323
TI  - Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production.
AB  - Antibiotic resistance is one of the most challenging global health threats in our
      society. Antimicrobial peptides (AMPs) represent promising alternatives to
      conventional antibiotics for the treatment of drug-resistant infections. However,
      they are limited by their high manufacturing cost. Engineering living organisms
      represents a promising approach to produce such molecules in an inexpensive
      manner. Here, we genetically modified the yeast Pichia pastoris to produce the
      prototypical AMP apidaecin Ia using a fusion protein approach that leverages the
      beneficial properties ( e.g., stability) of human serum albumin. The peptide was
      successfully isolated from the fusion protein construct, purified, and
      demonstrated to have bioactivity against Escherichia coli. To demonstrate this
      approach as a manufacturing solution to AMPs, we scaled-up production in
      bioreactors to generate high AMP yields. We envision that this system could lead
      to improved AMP biomanufacturing platforms.

PMID- 29366324
TI  - Screening of Chlorinated Paraffins and Unsaturated Analogues in Commercial
      Mixtures: Confirmation of Their Occurrences in the Atmosphere.
AB  - Characterizing the detailed compositions of chlorinated paraffins (CPs)
      commercial mixtures is crucial to understand their environmental sources, fates,
      and potential risks. In this study, dichloromethane (DCM)-enhanced UPLC-ESI
      QTOFMS analysis combined with characteristic isotope chlorine peaks is applied to
      screen all CPs and their structural analogues in the three most commonly produced
      CP commercial mixtures (CP-42, CP-52, and CP-70). Mass fractions of total short
      chain CPs (SCCPs), medium-chain CPs (MCCPs) and long-chain CPs (LCCPs) ranged
      from 0.64 to 31.9%, 0.64 to 21.8%, and 0.04 to 43.9%, respectively, in the three
      commercial mixtures. 113 unsaturated SCCPs, MCCPs, and LCCPs were identified in
      the commercial mixtures. The detailed mass percentages of saturated and
      unsaturated CPs with carbon numbers of 10-30, chlorine numbers of 5-28, and
      unsaturated degrees of 0-7 were characterized in all commercial mixtures.
      Occurrences of the predominant saturated and unsaturated CPs were further
      confirmed in air samples collected in Guangdong Province, one of the major CP
      production areas in China, over one year. The profiles of the detected compounds
      indicated that LCCPs in air samples might come mainly from the production and
      usage of CP-52, and unsaturated C24-29-LCCPs were specifically originated from CP
      70 used in the area.

PMID- 29366325
TI  - Toward Predictable 5'UTRs in Saccharomyces cerevisiae: Development of a yUTR
      Calculator.
AB  - Fine-tuning biosynthetic pathways is crucial for the development of economic
      feasible microbial cell factories. Therefore, the use of computational models
      able to predictably design regulatory sequences for pathway engineering proves to
      be a valuable tool, especially for modifying genes at the translational level. In
      this study we developed a computational approach for the de novo design of 5'
      untranslated regions (5'UTRs) in Saccharomyces cerevisiae with a predictive
      outcome on translation initiation rate. On the basis of existing data, a partial
      least-squares (PLS) regression model was trained and showed good performance on
      predicting protein abundances of an independent test set. This model was further
      used for the construction of a "yUTR calculator" that can design 5'UTR sequences
      with a diverse range of desired translation efficiencies. The predictive power of
      our yUTR calculator was confirmed in vivo by different representative case
      studies. As such, these results show the great potential of data driven
      approaches for reliable pathway engineering in S. cerevisiae.

PMID- 29366327
TI  - DNA-Polyelectrolyte Complexation Study: The Effect of Polyion Charge Density and
      Chemical Nature of the Counterions.
AB  - Complexes of polycations and DNA, also known as polyplexes, have been extensively
      studied in the past decade, as potential gene delivery systems. Their stability
      depends strongly on the characteristics of the polycations, as well as the nature
      of the added salt. We present here a study of the DNA ionene complexation in
      which we used fluorescence, UV, and CD spectroscopy, combined with molecular
      dynamics computer simuations, to systematically examine the influence of the
      polycation charge density, as well as the influence of the nature of the
      counterion, on the stability of these systems. Ionenes as polycations, depending
      on their structural characteristics, have previously been found to possess low
      cytotoxicity, and are therefore particularly interesting as potential gene
      delivery agents. The results show that the DNA solutions in the presence of the
      polycation are more stable in the case of very large or very small ionene charge
      density, suggesting different mechanism of complexation. The computer simulations
      show that the ionenes with high charge density bind to the minor groove of the
      DNA molecules, while the ionenes with lower charge density bind to the major
      groove of the DNA. The nature of the counterions play only a minor role:
      precipitation of the DNA molecules occurs at slightly lower ionene concentration
      when fluoride counterion are present, compared to the bromide counterions.

PMID- 29366328
TI  - Stream Mercury Export in Response to Contemporary Timber Harvesting Methods
      (Pacific Coastal Mountains, Oregon, USA).
AB  - Land-use activities can alter hydrological and biogeochemical processes that can
      affect the fate, transformation, and transport of mercury (Hg). Previous studies
      in boreal forests have shown that forestry operations can have profound but
      variable effects on Hg export and methylmercury (MeHg) formation. The Pacific
      Northwest is an important timber producing region that receives large atmospheric
      Hg loads, but the impact of forest harvesting on Hg mobilization has not been
      directly studied and was the focus of our investigation. Stream discharge was
      measured continuously, and Hg and MeHg concentrations were measured monthly for
      1.5 years following logging in three paired harvested and unharvested (control)
      catchments. There was no significant difference in particulate-bound Hg
      concentrations or loads in the harvested and unharvested catchments which may
      have resulted from forestry practices aimed at minimizing erosion. However, the
      harvested catchments had significantly higher discharge (32%), filtered Hg
      concentrations (28%), filtered Hg loads (80%), and dissolved organic carbon (DOC)
      loads (40%) compared to forested catchments. MeHg concentrations were low (mostly
      <0.05 ng L-1) in harvested, unharvested, and downstream samples due to well
      drained/unsaturated soil conditions and steep slopes with high energy eroding
      stream channels that were not conducive to the development of anoxic conditions
      that support methylation. These results have important implications for the role
      forestry operations have in affecting catchment retention and export of Hg
      pollution.

PMID- 29366329
TI  - Rationale and design of the SMaRT trial: A randomised, prospective, parallel, non
      blinded, one-centre trial to evaluate the use of magnetic resonance imaging in
      acute setting in patients presenting with suspected scaphoid fracture.
AB  - Background Wrist injury is a common presentation to the Emergency Department in
      the United Kingdom. Among these injuries, the scaphoid is the most common
      fractured carpal bone. However, given the limited ability of conventional
      radiography to accurately diagnose a suspected scaphoid fracture on presentation,
      its diagnosis and management remain challenging. Despite the vast clinical
      evidence supporting the superior accuracy of magnetic resonance imaging, there is
      little to no evidence around the real-world clinical and economic impact of
      immediate magnetic resonance imaging in the management of suspected scaphoid
      fractures. Methods Review of design and implementation challenges associated with
      the identification and subsequent recruitment of eligible patients,
      implementation of a novel clinical pathway in an acute setting, rationale behind
      the primary and secondary outcomes selected and measurement of the primary
      outcome. Results The Scaphoid Magnetic Resonance Imaging in Trauma trial is a
      single-site prospective, randomised, non-blinded, parallel design trial that aims
      to evaluate the use of immediate magnetic resonance imaging in the management of
      patients presenting to the acute setting with suspected scaphoid fractures. The
      primary outcome is the total 3-month cost per patient associated with the
      diagnosis and treatment of suspected scaphoid fractures. It is hypothesised that
      the immediate use of magnetic resonance imaging, a more accurate but expensive
      imaging modality, in patients with negative findings in the initial four-view
      radiography, will reduce the overall National Health Service costs by promoting
      definitive care and avoiding unnecessary diagnostic and treatment procedures.
      Other rationale design considerations in the recruitment, randomisation, data
      acquisition and intervention implementation are also discussed. Several of these
      challenges derive from real-world operational issues associated with the
      provision of magnetic resonance imaging in an intrinsically complex acute
      setting. Staff engagement during the trial's planning phase, combined with an
      extensive training programme rolled out prior to the trial's launch, were
      essential to raise staff awareness and engagement. Given the acute nature of the
      clinical condition, the latter was deemed essential as the eligibility
      assessment, recruitment, randomisation and treatment allocation processes all
      need to happen in a very tight time frame. Limitations Findings from the Scaphoid
      Magnetic Resonance Imaging in Trauma trial might not be generalisable to other
      National Health Service hospitals, foreign healthcare systems nor patient
      presentations outside normal magnetic resonance imaging working hours. Conclusion
      The Scaphoid Magnetic Resonance Imaging in Trauma trial was designed to evaluate
      the costs, patient satisfaction and clinical outcomes around the management of
      suspected scaphoid fractures and ultimately provide solid evidence on which to
      base the United Kingdom and international clinical practice. This article
      discusses the steps considered in the design of this novel trial, with particular
      emphasis on the issues and lessons learned during the planning and implementation
      stages.

PMID- 29366326
TI  - Detection of a Peptide Biomarker by Engineered Yeast Receptors.
AB  - Directed evolution of membrane receptors is challenging as the evolved receptor
      must not only accommodate a non-native ligand, but also maintain the ability to
      transduce the detection of the new ligand to any associated intracellular
      components. The G-protein coupled receptor (GPCR) superfamily is the largest
      group of membrane receptors. As members of the GPCR family detect a wide range of
      ligands, GPCRs are an incredibly useful starting point for directed evolution of
      user-defined analytical tools and diagnostics. The aim of this study was to
      determine if directed evolution of the yeast Ste2p GPCR, which natively detects
      the alpha-factor peptide, could yield a GPCR that detects Cystatin C, a human
      peptide biomarker. We demonstrate a generalizable approach for evolving Ste2p to
      detect peptide sequences. Because the target peptide differs significantly from
      alpha-factor, a single evolutionary step was infeasible. We turned to a substrate
      walking approach and evolved receptors for a series of chimeric intermediates
      with increasing similarity to the biomarker. We validate our previous model as a
      tool for designing optimal chimeric peptide steps. Finally, we demonstrate the
      clinical utility of yeast-based biosensors by showing specific activation by a C
      terminally amidated Cystatin C peptide in commercially sourced human urine. To
      our knowledge, this is the first directed evolution of a peptide GPCR.

PMID- 29366330
TI  - Practical Implementation of Failure Mode and Effects Analysis for Extracorporeal
      Membrane Oxygenation Activation.
AB  - Extracorporeal membrane oxygenation (ECMO) is used to treat severe hypoxemic
      respiratory failure and as a rescue therapy for patients with cardiopulmonary
      arrest within a narrow window of time. A failure modes and effects analysis
      (FMEA) was conducted to analyze the clinical and operational processes leading to
      delays in initiating ECMO. FMEA determined these highest-risk failure modes that
      were contributing to process failure: (1) ECMO candidacy not determined in time,
      (2) no or incomplete evaluation for ECMO prior to consult or arrest, (3) ECMO
      team not immediately available, and (4) cannulation not completed in time. When
      implemented collectively, a total of 4 interventions addressed more than 95% of
      the system failures. These interventions were (1) ECMO response pager held by a
      team required for decision, (2) distribution of institutionally defined
      inclusion/exclusion criteria, (3) educational training for clinicians consulting
      the ECMO team, and (4) establishment of a mobile ECMO insertion cart.

PMID- 29366331
TI  - Does Having Open Access to Care Improve Patient Experience? A Case-Control Study.
AB  - This study investigated whether primary and specialist care practices utilizing
      open access to care (OA) receive better patient experience scores than propensity
      matched control practices without OA. From March 2010 to December 2014, 711
      physicians classified as having OA in their practice, indicated by scoring 15 or
      higher on the OA checklist, were propensity matched to practices without OA.
      Patient experience was measured with 5 composites: timely care, communication,
      staff quality, care coordination, and overall physician rating. Minimally
      important differences in patient experience ratings were calculated between OA
      and control practices to determine optimal OA checklist scores. OA positively
      affected most composite domains for specialist practices, except physician
      rating, but minimally affected primary care practices. Practices scoring 19 or
      higher on the OA checklist had significantly higher patient-experience scores
      than matched controls. The authors recommend practices strive for 20 or higher on
      the OA checklist to see significant improvements in patient experience ratings.

PMID- 29366332
TI  - Genetics and Genomics in Nursing Science.

PMID- 29366333
TI  - Meanings and experiences associated with computer use of older immigrant adults
      of lower socioeconomic status: Les sens et les experiences associes a
      l'utilisation des ordinateurs chez les immigrants ages ayant un faible statut
      socioeconomique.
AB  - BACKGROUND: Immigrant older adults are a substantial demographic composing 12% to
      30% of older adults in the United States and Canada, yet no research has
      addressed the meanings associated with computer use for low-socioeconomic-status
      and immigrant older adults. PURPOSE: The study explored the meanings,
      occupational engagement, and experiences associated with computer use. METHOD: A
      mixed-methods approach, qualitative participatory action research (photovoice)
      and survey (Computer Proficiency Questionnaire), was used. Data collection
      consisted of narratives, focus groups, and Likert scale responses for nine
      participants. FINDINGS: The participants expressed the meanings they associated
      with computer use as freedom, personal growth, and engagement. Computers promote
      occupational engagement in social participation, education, and leisure.
      IMPLICATIONS: The findings of personal growth may inform occupational therapy
      interventions using computers to enable adjustment to changes related to aging
      and wellness. Social participation and education were motivators for computer
      use, which may inform computer engagement strategies for this population.

PMID- 29366334
TI  - Promoting Physical Activity Among University Students: A Systematic Review of
      Controlled Trials.
AB  - OBJECTIVE: University study is often accompanied by a decline in physical
      activity (PA) levels but can offer the opportunity to promote a lifelong active
      lifestyle. This review aims to summarize controlled trials of interventions
      promoting PA among university students, describing the quality of the evidence,
      effective strategies, and deficiencies in the interventions employed, to provide
      directions for future research and for practical implementations. DATA SOURCE:
      PubMed, PsychINFO, Cochrane Library, Education Source, and SPORTDiscus. Study
      Inclusion Criteria: Randomized or nonrandomized controlled trial, describing an
      intervention to promote PA in university students, where PA was one of the
      outcomes and results were published in English. DATA EXTRACTION: Country, study
      design, participants' inclusion criteria, participation rate and characteristics,
      randomization, blinding, theoretical framework, intervention characteristics,
      participant retention rate and withdrawal reasons, measures employed, data
      analysis, PA results, and findings regarding PA correlates. DATA SYNTHESIS: Data
      were synthetized considering study characteristics, strategies used, and
      outcomes. RESULTS: Two thousand five hundred eighty-five articles were
      identified. Twenty-seven studies met the inclusion criteria. Sixteen studies
      reported an increase in PA levels. CONCLUSION: Physical Activity promotion
      interventions should address a range of behavioral determinants. Personalized
      approaches and PA sessions should be considered in future studies. The high risk
      of bias of many studies (mainly due to attrition and poor reporting) and missing
      information about intervention components limit the strength of conclusions about
      the most effective strategies and the evidence of effectiveness, highlighting the
      need for further high-quality studies.

PMID- 29366335
TI  - Fib3-3 as a Biomarker for Osteoarthritis in a Rat Model with Metabolic
      Dysregulation.
AB  - Objective Fibulin-3 is a glycoprotein highly expressed in osteoarthritic
      cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent
      studies have indicated that fibulin-3 has potential value as a biomarker in
      osteoarthritis. The aim of the present study is to examine the role of 3 fibulin
      3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation
      product in a rat osteoarthritis model with systemic metabolic alterations
      combined with local cartilage damage. Design Forty, 12-week-old male, Wistar rats
      were randomly divided over 2 groups: a standard or a high-fat diet inducing
      metabolic dysregulation. After 12 weeks, articular cartilage damage was induced
      on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet
      group. At endpoint, blood was collected and serum was isolated. Enzyme-linked
      immunosorbent assay on all selected fibulin-3 fragments was performed from serum
      samples in addition to immunohistochemical analysis for Fib3-3. Results Serum
      concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was
      induced in addition to a high-fat diet. Fib3-3 was also associated with an
      increased histological total joint degeneration ( r = 0.435) and cartilage
      degeneration ( r = 0.435). Immunostainings demonstrated increased Fib3-3 in the
      superficial cartilage of animals with high-fat diet and/or cartilage damage.
      Conclusions In the rat groove model combined with high-fat diet-induced metabolic
      dysregulation an increased Fib3-3 concentration was observed systemically, which
      is associated with local joint degeneration. This suggests that systemic Fib3-3
      concentrations can indicate the status of joint degeneration and function as a
      biomarker in osteoarthritis.

PMID- 29366336
TI  - End-of-Life Decision-Making for Patients With Geriatric Trauma Cared for in a
      Trauma Intensive Care Unit.
AB  - BACKGROUND: The geriatric trauma population is growing and fraught with poor
      physiological response to injury and high mortality rates. Our primary hypothesis
      analyzed how prehospital and in-hospital characteristics affect decision-making
      regarding continued life support (CLS) versus withdrawal of care (WOC). Our
      secondary hypothesis analyzed adherence to end-of-life decisions regarding code
      status, living wills, and advanced directives. MATERIALS AND METHODS: We
      performed a retrospective review of patients with geriatric trauma at a level I
      and level II trauma center from January 1, 2007, to December 31, 2014. Two
      hundred seventy-four patients met inclusion criteria with 144 patients undergoing
      CLS and 130 WOC. RESULTS: A total of 13 269 patients with geriatric trauma were
      analyzed. Insurance type and injury severity score (ISS) were found to be
      significant predictors of WOC ( P = .013/.045). Withdrawal of care patients had
      shorter time to palliative consultation and those with geriatrics consultation
      were 16.1 times more likely to undergo CLS ( P = .026). Twenty-seven (33%)
      patients who underwent CLS and 31 (24%) patients who underwent WOC had a living
      will, advanced directive, or DNR order ( P = .93). CONCLUSIONS: Of the many
      hypothesized predictors of WOC, ISS was the only tangible independent predictor
      of WOC. We observed an apparent disconnect between the patient's wishes via
      living wills or advanced directives "in a terminal condition" and fulfillment
      during EOL decision-making that speaks to the complex nature of EOL decisions and
      further supports the need for a multidisciplinary approach.

PMID- 29366337
TI  - Extensive Cutaneous Botryomycosis With Subsequent Development of Nocardia
      Positive Wound Cultures.
AB  - Botryomycosis is a rare, chronic granulomatous infection caused by a response to
      bacteria, most commonly Staphylococcus aureus. Cutaneous manifestations, such as
      subcutaneous nodules, nonhealing ulcers, or sinus tracks, typically occur
      following inoculation of bacteria after trauma. Drainage from the skin lesions
      may contain yellow grains resembling those seen in actinomycosis and nocardiosis.
      A 20-year-old Hispanic male presented over the course of several years with a
      chronic nonhealing left posterior scalp wound. A car hit the patient when he was
      2 years old and injured the scalp in the location of the skin lesion. Multiple
      wound cultures grew methicillin-resistant Staphylococcus aureus (MRSA), and
      biopsies were consistent with botryomycosis. He was treated with multiple
      surgical debridements, skin grafts, and various courses of oral and intravenous
      antibiotics with slight improvement. One reason for poor response to therapy was
      noncompliance with long-term home antibiotics. The most recent tissue culture
      grew MRSA in addition to Nocardia mexicana, and he experienced improvement on
      linezolid and minocycline. Although it is important to exclude nocardiosis and
      actinomycosis when diagnosing botryomycosis, our patient was diagnosed with
      botryomycosis after multiple biopsies and positive MRSA cultures 2 years prior to
      1 positive N mexicana culture. Our case is a unique presentation of botryomycosis
      in an individual who subsequently developed Nocardia-positive wound cultures.

PMID- 29366339
TI  - Default Mode Network Engagement Beyond Self-Referential Internal Mentation.
AB  - The default mode network (DMN) is typically associated with off-task internal
      mentation, or with goal-oriented tasks that require self-referential processing
      such as autobiographical planning. However, recent reports suggest a broader
      involvement of the DMN in higher cognition. In line with this view, we report
      global connectivity changes that are centered on the main DMN hubs of precuneus
      and posterior cingulate cortex during a functional magnetic resonance imaging
      based visuospatial version of the Tower of London planning task. Importantly,
      functional connectivity of these regions with the left caudate shows a
      significant relationship with faster reaction time to correct responses only
      during the high-demand planning condition, thus offering further evidence for the
      DMN's engagement during visuospatial planning. The results of this study not only
      provide robust evidence against the widely held notion of DMN disengagement
      during goal-oriented, attention-demanding, externally directed tasks but also
      support its involvement in a broader cognitive context with a memory-related role
      that extends beyond self-referential, internally directed mentation.

PMID- 29366338
TI  - The clinicopathological features and prognosis of tumor MSI in East Asian
      colorectal cancer patients using NCI panel.
AB  - AIM: To compare test results obtained from a PCR assay for the National Cancer
      Institute (NCI) five loci criteria for detecting microsatellite instability (MSI)
      with those obtained from immunohistochemistry of mismatch repair and a five
      mononucleotide site amplification system in East Asian patients with colorectal
      cancer. PATIENTS & METHODS:  A total of 245 East Asian patients with colorectal
      cancer were studied retrospectively at our institution. RESULTS: The consistency
      of the NCI panel PCR method compared with detection of mismatch repair protein
      expression by immunohistochemistry was 0.898. High level MSI (MSI-H) status was
      correlated with the Tumor, Node, Metastasis stage, tumor location site,
      metastasis, tumor grade, mucinous histological type and BRAF-type mutations.
      CONCLUSION: The NCI panel PCR assay has excellent sensitivity and specificity for
      detecting MSI in an East Asian population.

PMID- 29366340
TI  - Effects of strength exercise on the knee and ankle proprioception of individuals
      with knee osteoarthritis.
AB  - This study aims to investigate the effects of 8-week strength exercise on knee
      and ankle proprioception of individuals with knee osteoarthritis (KOA). Forty
      participants were randomly divided into control and strength exercise groups.
      Strength exercise group underwent squat training of three times a week for 8
      weeks, while control group received an education programme. Threshold for
      detection of passive movement of knee and ankle joint was tested using an
      electrically driven movable frame. Between- and within-group differences were
      evaluated through repeated-measurement analysis of variance. After intervention,
      passive motion sense in knee flexion of participants in strength exercise group
      significantly improved (p = 0.033, 95% confidence interval of mean difference:
      0.019-1.478) with significant difference between groups. No significant
      differences of passive motion senses were found in knee extension and ankle
      between strength exercise and control groups. Eight-week squat training
      significantly improves the motion sense of knee flexion in patients with KOA.

PMID- 29366341
TI  - Use of 3D Prints to Compare the Efficacy of Three Different Calcaneal Osteotomies
      for the Correction of Heel Varus.
AB  - BACKGROUND: Cavovarus deformity of the hindfoot is typically caused by neurologic
      disorders. Multiple osteotomies have been described for the correction of varus
      deformity but without clinical comparison. In this study, we used 18 identical 3
      dimensional (3D) prints of a patient with heel varus to compare the operative
      correction obtained with Dwyer, oblique, and Z osteotomies. METHODS: A computed
      tomography (CT) scan of a patient with heel varus was used to create 18 identical
      3D prints of the talus, calcaneus, and cuboid. Coordinate frames were added to
      the talus and calcaneus to evaluate rotation. The prints were then divided into 3
      groups of 6 models each. A custom jig precisely and accurately replicated each
      osteotomy. Following the simulated operations, cut models were CT scanned and
      compared with 6 uncut models. Measurements were calculated using multiplanar
      reconstruction image processing. An analysis of variance (ANOVA) was performed on
      the initial data to determine significant differences among the measured
      variables. A Tukey Studentized range test was run to compare variables that
      showed statistically significant differences using the ANOVA. RESULTS: The
      coronal angle of the Dwyer and oblique osteotomies was significantly less than
      that of the Z osteotomy ( P < .05). The axial angle, lateral displacement, and
      calcaneal shortening of the uncut model and Z osteotomy were significantly less
      than the Dwyer and oblique osteotomies. CONCLUSIONS: Dwyer, oblique, and Z
      osteotomies did not create either lateral translation or coronal rotation without
      the addition of a lateralizing slide or rotation of the posterior tuberosity.
      CLINICAL RELEVANCE: Dwyer and oblique osteotomies would be best suited for mild
      deformity, yet the amount of calcaneal shortening must be acknowledged. A Z
      osteotomy is a complex procedure that has the capability of correcting moderate
      severe coronal plane rotation but fails to provide lateralization of the pull of
      the Achilles insertion.

PMID- 29366342
TI  - Long-term Follow-up of Revision Osteochondral Allograft Transplantation of the
      Ankle.
AB  - BACKGROUND: Osteochondral allograft (OCA) transplantation is a useful alternative
      for treatment of posttraumatic ankle arthritis in young patients but has a
      relatively high failure rate and further procedures are often required. The
      purpose of this study was to evaluate outcomes of patients who underwent revision
      OCA transplantation of the ankle after failed primary OCA transplantation.
      METHODS: Twenty patients underwent revision OCA transplantation of the ankle
      between 1988 and 2015. Mean age was 44 years, 55% (11 of 20) were female. The
      mean time from primary to revision OCA was 3.0 +/- 1.7 years. All patients had a
      minimum follow-up of 2 years. Outcomes included the American Academy of
      Orthopaedic Surgeons Foot and Ankle Module (AAOS-FAM) and questionnaires
      evaluating pain and satisfaction. Failure of the revision OCA was defined as a
      conversion to arthroplasty, arthrodesis, or amputation. RESULTS: Ten of 20 ankles
      required further surgery, of which 30% (6 of 20) were considered OCA revision
      failures (4 arthrodeses, 1 arthroplasty, and 1 amputation). The mean time to
      failure was 6.7 (range, 0.6-13.1) years. Survivorship of the revision OCA was 84%
      at 5 years and 65% at 10 years. The 14 patients with grafts remaining in situ had
      an average follow-up of 10.3 years; mean AAOS-FAM Core Score was 70.5 (range,
      42.3-99). Of the patients who answered the follow-up questions, 4 of 7 reported
      moderate to severe pain, and 5 of 12 were satisfied with the results of the
      procedure. CONCLUSION: Although the results of revision ankle OCA transplantation
      are not inferior to primary OCA transplantation, the high rates of persistent
      pain, further surgery, and graft failure suggest that the indications for OCA as
      a revision procedure should be carefully evaluated, with proper patient
      selection. Considering the treatment alternatives, revising a failed OCA
      transplantation can be a useful treatment option, especially for young and active
      patients who wish to avoid arthrodesis or arthroplasty. LEVEL OF EVIDENCE: Level
      IV, case series.

PMID- 29366343
TI  - Implementation of Patient-Reported Outcomes Measurement Information System Data
      Collection in a Private Orthopedic Surgery Practice.
AB  - BACKGROUND: The authors describe a method of collecting patient-reported outcomes
      (PROs) using computerized adaptive tests (CATs) in a high-volume orthopedic
      surgery practice with limited resources and no research coordinator. METHODS:
      Patient-Reported Outcomes Measurement Information System CATs were collected
      prospectively for all clinic patients using a tablet and recorded in the
      electronic medical record. Scores were compared with validated national norms
      using single-variable t tests. Linear regression was used to assess age effects.
      Preoperative and postoperative pain scales were compared using paired t tests.
      RESULTS: In total, 4,524 CATs were administered during 10,719 visits (42%),
      reaching 70% as more tablets were introduced. Completing the CATs required 157
      seconds. Older patients took more time than younger ones ( P < .05). Compared
      with normalized t scores of 50 +/- 10 for the US population, pain intensity was
      48.0 (95% confidence interval [CI], 47.8-48.2), pain interference 58.9 (95% CI,
      58.6-59.1), physical function 40.1 (95% CI, 39.9-40.3), global physical health
      43.4 (95% CI, 41.9-44.9), and global mental health 41.1 (95% CI, 40.89-41.4) ( P
      < .05 for all). Age had a small effect on all domains ( P < .05). Approximately
      20 patients would be required to demonstrate a 15% change for a 2-tailed, paired
      study with alpha = 0.05 and 80% power. After surgery, pain intensity improved
      from 51.9 +/- 8.2 to 44.1 +/- 8.5, pain interference improved from 62.5 +/- 6.9
      to 55.7 +/- 8.4, and physical function improved from 37.3 +/- 8.9 to 41.5 +/- 7.9
      ( P < .05 for all). CONCLUSIONS: Using tablets to administer CATs and entering
      the data in the electronic medical record for later retrieval was an effective
      technique to collect PROs. An adequate number of tablets are needed for
      acceptable completion rates. Modest sample size requirements for comparative
      studies highlight the potential of these tools and techniques. LEVEL OF EVIDENCE:
      Level II, Prospective Comparative Study.

PMID- 29366344
TI  - Complications After Multiple-Site Peripheral Nerve Blocks for Foot and Ankle
      Surgery Compared With Popliteal Sciatic Nerve Block Alone.
AB  - BACKGROUND: Single or combined multiple-site peripheral nerve blocks (PNBs) are
      becoming popular for patients undergoing surgery on their feet or ankles. These
      procedures are known to be generally safe in surgical settings compared with
      other forms of anesthesia, such as spinal block. The purposes of this study were
      to assess the incidence of complications after the administration of multiple
      PNBs for foot and ankle surgery and to compare the rates of complications between
      patients who received a single PNB and those who received multiple blocks.
      METHODS: Charts were reviewed retrospectively to assess peri- and postoperative
      complications possibly related to the PNBs. The records of 827 patients who had
      received sciatic nerve blocks, femoral nerve blocks adductor canal blocks, or
      combinations of these for foot and/or ankle surgery were analyzed for
      complications. The collected data consisted of age, sex, body mass index,
      presence of diabetes mellitus, smoking history, tourniquet time, and
      complications both immediately postoperatively and 1 year later. RESULTS: Of
      these 827 patients, 92 (11.1%) developed neurologic symptoms after surgery; 22
      (2.7%) of these likely resulted from the nerve blocks, and 7 (0.8%) of these were
      unresolved after the patients' last follow-up visits. There were no differences
      in complication rates between combined blocks and single sciatic nerve blocks.
      CONCLUSION: There were more complications, both transient and long term, after
      anesthetic PNBs than previous literature has reported. Combined multiple-site
      blocks did not increase the rate of neurologic complications. LEVEL OF EVIDENCE:
      Level III, retrospective comparative study.

PMID- 29366345
TI  - Perceptions and experiences regarding the impact of race on the quality of
      healthcare in Southeast Brazil: a qualitative study.
AB  - OBJECTIVE: To explore the impact of race on the quality of healthcare received by
      patients attending a primary care centre in Brazil. DESIGN: This was a
      qualitative study consisting of 19 semi-structured interviews conducted on
      patients from six racial groups (as defined in Brazil as white, yellow, brown,
      black and indigenous and one self-identified 'other' group). The interviews were
      analysed using thematic analysis. RESULTS: Four main themes were identified
      during analysis; factors affecting the access to healthcare, experiences
      regarding quality of healthcare, discrimination in healthcare and deep-rooted
      societal discrimination, which were categorised into a number of sub-themes.
      Within these themes, interviewees reported (1) experiences of racism in society
      towards the black racial group, (2) one personal perception and two observations
      of racial discrimination in healthcare, (3) perceived racial discrimination due
      to healthcare professional behaviour and (4) other factors, such as delays in
      appointments and long waiting times in health facilities were felt to impact
      access to care. CONCLUSION: The findings suggest that racial discrimination
      exists in Brazilian society but its direct impact on healthcare access was felt
      to be less obvious. Instead, organisational level factors were felt to contribute
      to difficulty accessing care. Interviewees perceived that racial discrimination
      may affect the quality of care, particularly for those designated as 'black'.
      Socio-economic factors were felt to influence discrimination in healthcare. The
      findings can help inform further studies and educational initiatives to help
      address discrimination and access to healthcare in Brazil.

PMID- 29366346
TI  - Microwave ablation induces a lower systemic stress response in patients than open
      surgery for treatment of benign thyroid nodules.
AB  - OBJECTIVE: In this study, we compared the systemic stress response induced by
      microwave ablation with that induced by conventional open surgery for treatment
      of benign thyroid nodules. METHODS: A total of 108 patients with benign thyroid
      nodules were randomly assigned to receive ultrasound-guided thyroid microwave
      ablation (microwave group, n = 57) and conventional open thyroid surgery (open
      group, n = 51). Body temperature, white blood cell (WBC) counts, visual analogue
      scale (VAS) scores for pain, and serum levels of high sensitive C-reactive
      protein (hs-CRP), interleukin 6 (IL-6) and cortisol were measured at 24 h before
      operation and at 8 h, 24 h and 48 h after operation. RESULTS: No significant
      between-group differences were observed with respect to preoperative body
      temperature, VAS scores, WBC counts, serum hs-CRP, IL-6 and cortisol levels.
      Patients in the open group exhibited higher body temperature at 24 h after
      operation and higher WBC counts at both 24 h and 48 h after operation, as
      compared to those in the microwave group. As compared with microwave ablation,
      open surgery was associated with significantly higher VAS scores, and
      significantly higher serum levels of hs-CRP, IL-6 and cortisol at all
      postoperative time-points (8 h, 24 h and 48 h). CONCLUSION: Microwave ablation
      induces a lower systemic stress response than open surgery for treatment of
      benign thyroid nodules.

PMID- 29366348
TI  - Case report: an identical twin with Sertoli-Leydig cell tumor.
AB  - Our report details the workup and management of a 43-year-old woman with an
      identical twin who presented with 2 years of virilization and secondary
      amenorrhea. Serum total testosterone was elevated. An MRI did not identify
      adnexal or adrenal pathology. Subsequent ovarian vein sampling demonstrated
      unilateral testosterone elevation. The patient underwent laparoscopic unilateral
      oophorectomy resulting in the diagnosis of Sertoli-Leydig cell tumor (SLCT).
      Although SLCT is a rare sex-cord ovarian tumor, it is associated with endometrial
      hyperplasia and malignancy. Our goals are to review the workup of androgen
      secreting tumors and discuss the clinical importance of the DICER1 mutation in
      the context of SLCT. In this case, an identical twin underwent DICER1 testing
      which was one of the essential steps in her clinical management.

PMID- 29366347
TI  - Correlation of hospital magnet status with the quality of physicians performing
      neurosurgical procedures in New York State.
AB  - PURPOSE: The quality of physicians practicing in hospitals recognized for nursing
      excellence by the American Nurses Credentialing Center has not been studied
      before. We investigated whether Magnet hospital recognition is associated with
      higher quality of physicians performing neurosurgical procedures. MATERIALS AND
      METHODS: We performed a cohort study of patients undergoing neurosurgical
      procedures from 2009-2013, who were registered in the New York Statewide Planning
      and Research Cooperative System (SPARCS) database. Propensity score adjusted
      multivariable regression models were used to adjust for known confounders, with
      mixed effects methods to control for clustering at the facility level. An
      instrumental variable analysis was used to control for unmeasured confounding and
      simulate the effect of a randomized trial. RESULTS: During the study period,
      185,277 patients underwent neurosurgical procedures, and met the inclusion
      criteria. Of these, 66,607 (35.6%) were hospitalized in Magnet hospitals, and
      118,670 (64.4%) in non-Magnet institutions. Instrumental variable analysis
      demonstrated that undergoing neurosurgical operations in Magnet hospitals was
      associated with a 13.6% higher chance of being treated by a physician with
      superior performance in terms of mortality (95% CI, 13.2% to 14.1%), and a 4.3%
      higher chance of being treated by a physician with superior performance in terms
      of length-of-stay (LOS) (95% CI, 3.8% to 4.7%) in comparison to non-Magnet
      institutions. The same associations were present in propensity score adjusted
      mixed effects models. CONCLUSIONS: Using a comprehensive all-payer cohort of
      neurosurgical patients in New York State we identified an association of Magnet
      hospital recognition with superior physician performance.

PMID- 29366350
TI  - Analysis of the reduction of trans-fatty-acid levels in the foods of Argentina.
AB  - Adverse health effects found to be caused by the industrial trans fatty acids
      (TFAs) encouraged significant changes in the food supply. A working model was
      implemented based on a multisectoral approach to monitor progress in the
      reduction of TFAs in compliance with Argentine food regulations. We analysed the
      fatty-acid profiles of commercial foods over the entire country comparing the
      results before and after the deadline for the compliance. A 93% adherence in the
      foods was obtained after the finalisation of the deadline for the compliance with
      the limited use of partially hydrogenated vegetable oils. The analytical
      monitoring was a key tool operating for the compliance by the food manufacturers.
      The industrial TFAs were mostly replaced by semisolid fractions of vegetable oils
      containing high percentages of saturated fatty acids. Promising innovations for
      the food industry were established that provided more healthful alternative
      substitutes for TFAs.

PMID- 29366349
TI  - Gadolinium-doped hollow CeO2-ZrO2 nanoplatform as multifunctional MRI/CT dual
      modal imaging agent and drug delivery vehicle.
AB  - Developing multifunctional nanoparticle-based theranostic platform for cancer
      diagnosis and treatment is highly desirable, however, most of the present
      theranostic platforms are fabricated via complicated structure/composition design
      and time-consuming synthesis procedures. Herein, the multifunctional Gd/CeO2
      ZrO2/DOX-PEG nanoplatform with single nano-structure was fabricated through a
      facile route, which possessed MR/CT dual-model imaging and chemotherapy ability.
      The nanoplatform not only exhibited well-defined shapes, tunable compositions and
      narrow size distributions, but also presented a well anti-cancer effect and MR/CT
      imaging ability. Therefore, the Gd/CeO2-ZrO2/DOX-PEG nanoplatform could be
      applied for chemotherapy as well as dual-model MR/CT imaging.

PMID- 29366351
TI  - Histomorphometric changes in the placenta and umbilical cord during complications
      of pregnancy.
AB  - Pregnancy complications may cause morphological changes and circulation defects
      in the placenta, which may lead to morbidity and mortality in fetuses and
      newborns. We investigated structural changes in the placenta and umbilical cord
      under various abnormal maternal conditions. Placenta and umbilical cord specimens
      were obtained from pregnant women during labor at 37 - 42 weeks gestation.
      Volumetric measurements were made for each placenta and umbilical cord using the
      Cavalieri method. Significant differences were observed for volumetric densities
      of total villi, syncytial knots, intervillous vessels and perivillous fibrin
      deposition. We observed particular increases in the volumetric parameters of the
      pre-eclampsia group compared to the other groups. The tunica media of the
      umbilical arteries was increased significantly with intrahepatic cholestasis.

PMID- 29366352
TI  - Gene Therapy for Hemophilia and Duchenne Muscular Dystrophy in China.
AB  - Gene therapy is a new technology that provides potential for curing monogenic
      diseases caused by mutations in a single gene. Hemophilia and Duchenne muscular
      dystrophy (DMD) are ideal target diseases of gene therapy. Important advances
      have been made in clinical trials, including studies of adeno-associated virus
      vectors in hemophilia and antisense in DMD. However, issues regarding the high
      doses of viral vectors required and limited delivery efficiency of antisense
      oligonucleotides have not yet been fully addressed. As an alternative strategy to
      classic gene addition, genome editing based on programmable nucleases has also
      shown promise to correct mutations in situ. This review describes the recent
      progress made by Chinese researchers in gene therapy for hemophilia and DMD.

PMID- 29366353
TI  - Effect of early use of low-dose aspirin therapy on late-onset preeclampsia.
AB  - OBJECTIVE: Low-dose aspirin (LDA) therapy has been found to be effective in
      preventing the development of early-onset preeclampsia. However, its effect on
      late-onset preeclampsia has not been described. Our study was aimed at
      determining if LDA therapy prescribed from early in pregnancy modified the
      severity of late-onset preeclampsia. MATERIALS AND METHODS: A retrospective
      analysis of all women who were screened for early-onset preeclampsia at 11-13+6
      weeks' gestation between April 2012 and October 2014 at our institution, and who
      subsequently developed late-onset preeclampsia. The treatment group consisted of
      women who were prescribed LDA therapy from early in pregnancy as a result of the
      screening. The control group consisted of women who did not receive LDA therapy.
      RESULTS: The aspirin group was associated with earlier delivery at 38.0 (37.5
      38.5) weeks' gestation versus 39.0 (38.7-39.4) weeks' gestation for the
      nonaspirin group (p < .01). The aspirin group was also associated with lower
      absolute birth weight 2851 (2646-3055) versus 3215 (3068-3362) grams in the
      nonaspirin group (p < .01). However, when normalised for gestational age at
      delivery, the proportion of foetuses that were small for gestation age (< 10th
      centile) were not significantly different between the two groups [28% in aspirin
      group versus 23% in nonaspirin group; p = .62]. No other significant difference
      was noted. CONCLUSIONS: There was no difference in the clinical severity of late
      onset preeclampsia between women screened as high risk for early-onset
      preeclampsia and subsequently prescribed LDA during their pregnancy, compared to
      women found to be at low risk and not prescribed LDA.

PMID- 29366355
TI  - Direct player observation is needed to accurately quantify heading frequency in
      youth soccer.
AB  - In soccer, heading may be related to subsequent neurological impairment. Accurate
      measures of heading exposure are therefore important. This study evaluated
      whether 12 female youth players accurately recalled their average number of
      headers over an entire soccer season (20 games total). Their self-reported
      average number of headers per game was multiplied by the number of games that
      they participated in, and were compared to actual number of headers extracted
      from game video. All players overestimated the number of headers compared to game
      video. Linear regression analysis indicated that self-reported headers
      overestimated the number of headers by 51%. While self-reports are a convenient
      way to estimate heading behaviour, they do not accurately represent the number of
      headers that players perform. Self-reports of heading exposure should be
      interpreted with caution.

PMID- 29366354
TI  - Dietary habits and energy balance in an under 21 male international soccer team.
AB  - Soccer presents a metabolic challenge which is not necessarily matched by
      players' habitual dietary intake. To examine the effects of a bespoke diet, 22
      players completed the Ball Sport Endurance and Sprint Test (BEAST90mod) protocol,
      followed by 4 days of regulated nutritional intake. The diet consisted of 10 g?kg
      1 body mass (BM) and 1.7 g?kg-1 BM of carbohydrate and protein, respectively. On
      day 5, players followed a prematch nutritional strategy of 7 g?kg-1 BM of
      carbohydrate and 1 g?kg-1 BM of protein divided into three meals and then
      repeated the BEAST90mod. The players' pre-intervention intake consisted of 49 +/-
      7.1% or 3.5 g +/- 1.0 g?kg-1 BM for carbohydrate and 19 +/- 3.8% of total daily
      energy intake or 1.3 g +/- 0.5 g?kg-1 BM for protein. Following the tailor-made
      dietary intervention, players ran an additional 887 +/- 233 m (8.1%; d = 2.4). An
      acute dietary intervention provided a positive effect on a valid simulated soccer
      match play test.

PMID- 29366357
TI  - Measuring the flashbulb-like nature of memories for private events: the flashbulb
      memory checklist.
AB  - What do we remember following an emotionally charged event? The assessment of
      memory characteristics for an emotional event represents one of the most
      challenging issues in the domain of autobiographical memory. Literature of
      flashbulb memories (FBMs) provides a crucial contribution on this issue:
      Following an emotional and unexpected public event, people remember not only
      central details of the episode, but also irrelevant, peripheral and idiosyncratic
      details of the reception context in which they learned of the news. The present
      study was set up to assess the factorial structure (samples 1 and 2) and
      convergent validity (sample 2) of an FBM checklist, an instrument designed to
      measure Flashbulb-like features of memories for emotional private events.
      Factorial analyses account for an oblique two-factor solution - FBM Specificity
      and Confidence - while correlational analyses support the convergent validity of
      this instrument. Practical implications are discussed, especially for the
      credibility assessment of witnesses of emotional events in forensic settings.

PMID- 29366356
TI  - Therapeutic bispecific antibody formats: a patent applications review (1994
      2017).
AB  - INTRODUCTION: Bispecific antibodies have become increasingly of interest by
      enabling new therapeutic applications such as retargeting cellular immunity
      towards tumor cells. About 23 bispecific antibody platforms have therefore been
      developed, generating about 62 molecules which are currently being evaluated for
      potential treatment of a variety of indications, such as cancer and inflammatory
      diseases, among which three molecules were approved. This class of drugs will
      represent a multi-million-dollar market over the coming years. Many companies
      have consequently invested in the development of bispecific antibody platforms,
      creating an important patent activity in this field. Areas covered: The present
      review gives an overview of the patent literature over the period 1994-2017 of
      different immunoglobulin gamma-based bispecific antibody platforms and the
      molecules approved or in clinical trials. Expert opinion: Bispecific antibodies
      are progressively accepted as potentially superior therapeutic molecules in a
      broad range of diseases. This frantic activity creates a maze of hundreds of
      patents that pose considerable legal risks for both newcomers and established
      companies. It can consecutively be anticipated that the number of patent
      conflicts will increase. Nevertheless, it can be expected that patents related to
      the use of a bispecific antibody will have tremendous commercial value.

PMID- 29366358
TI  - Fasting glucose concentrations and associations with reproductive history over 40
      years of follow-up.
AB  - Gestational diabetes mellitus (GDM) is the onset or first recognition of diabetes
      that occurs during pregnancy. We aimed to assess for trends in fasting blood
      glucose levels across the life-course among a cohort of women by reproductive
      history: nulligravid women, gravid women with and without a history of GDM. Women
      who had participated in the Bogalusa Heart Study as children were interviewed
      about their reproductive history, including GDM (n = 358). We compared fasting
      blood glucose (mg/dL) measured after last pregnancy (or after age 40 among
      nulligravid women) across reproductive history groups in linear models adjusted
      for prepregnancy fasting blood glucose, body mass index, race, parity, and age at
      outcome measure. We fit a log-Poisson model to estimate the associations with
      prediabetes risk after age 40. After adjustments, mean fasting glucose after age
      40 was not different between gravid women without GDM history and nulligravid
      women. However, women with a history of GDM had mean fasting glucose 27 mg/dL
      greater than nulligravid women (95% CI = 12.35, 41.64). Heterogeneity by race
      indicated Black women with a history of GDM had disproportionately elevated mean
      fasting glucose after age 40. Fasting blood glucose trends over the life-course
      differ among women by reproductive history and race.

PMID- 29366359
TI  - Health-related knowledge on hypertension among the Portuguese population: results
      from a population-based survey.
AB  - PURPOSE: Adequate knowledge on hypertension has been shown to improve awareness,
      adherence to treatment and control of the disease. We aimed to estimate the
      health-related knowledge about hypertension among the Portuguese population.
      MATERIALS AND METHODS: A representative sample of Portuguese-speaking dwellers in
      mainland Portugal (n = 1624), aged 16 to 79 years, was evaluated through face-to
      face interviews conducted using a structured questionnaire. Health literacy was
      evaluated using the instrument Newest Vital Sign. RESULTS: The mean prevalence of
      hypertension in the Portuguese population estimated by the participants in this
      study was 45.4%. Salt intake and poor diet were reported as main causes of
      hypertension by 27.5% and 21.5% of the participants, respectively, whereas more
      than 85% acknowledged myocardial infarction and stroke as its main consequences.
      However, 31.2% of the participants were not able to identify a cause for high
      blood pressure, especially the older and those with worse scores for health
      literacy. The accurate interpretation of blood pressure values diminished with
      the increase of systolic and diastolic blood pressure figures provided as
      examples for interpretation, from approximately 80% for 95/60 mmHg to 50% for
      180/100 mmHg. Women and participants with greater levels of education or a
      previous diagnosis of hypertension tended to interpret blood pressure values
      correctly more often. CONCLUSIONS: This study provided a quantitative estimate of
      the gaps in health-related knowledge about hypertension among the general
      population. Understanding the barriers that hinder the achievement of health
      related knowledge on hypertension is expected to contribute for the global
      improvement of prevention and management of hypertension.

PMID- 29366360
TI  - Silk fibroin nanoparticles dyeing indocyanine green for imaging-guided photo
      thermal therapy of glioblastoma.
AB  - Silk was easily dyed in traditional textile industry because of its strong
      affinity to many colorants. Herein, the biocompatible silk fibroin was firstly
      extracted from Bombyx mori silkworm cocoons. And SF nanoparticles (SFNPs) were
      prepared for dyeing indocyanine green (ICG) and construct a therapeutic nano
      platform (ICG-SFNPs) for photo-thermal therapy of glioblastoma. ICG was easily
      encapsulated into SFNPs with a very high encapsulation efficiency reaching to
      97.7 +/- 1.1%. ICG-SFNPs exhibited a spherical morphology with a mean particle
      size of 209.4 +/- 1.4 nm and a negative zeta potential of -31.9 mV, exhibiting a
      good stability in physiological medium. Moreover, ICG-SFNPs showed a slow release
      profile of ICG in vitro, and only 24.51 +/- 2.27% of the encapsulated ICG was
      released even at 72 h. Meanwhile, ICG-SFNPs exhibited a more stable photo-thermal
      effect than free ICG after exposure to near-infrared irradiation. The temperature
      of ICG-SFNPs rapidly increased by 33.9  degrees C within 10 min and maintained
      for a longer time. ICG-SFNPs were also easily internalized with C6 tumor cells in
      vitro, and a strong red fluorescence of ICG was observed in cytoplasm for
      cellular imaging. In vivo imaging showed that ICG-SFNPs were effectively
      accumulated inside tumor site of C6 glioma-bearing Xenograft nude mice through
      vein injection. Moreover, the temperature of tumor site was rapidly rising up to
      kill tumor cells after local NIR irradiation. After treatment, its growth was
      completely suppressed with the relative tumor volume of 0.55 +/- 033 while free
      ICG of 33.72 +/- 1.90. Overall, ICG-SFNPs may be an effective therapeutic means
      for intraoperative phototherapy and imaging.

PMID- 29366362
TI  - Erratum.

PMID- 29366361
TI  - Role of time-resolved-CTA in intracranial arteriovenous malformation evaluation
      at 128-slice CT in comparison with digital subtraction angiography.
AB  - Introduction The present study aimed to evaluate the accuracy of time-resolved
      computed tomographic angiography (TR-CTA) on a 128-slice CT scanner vis-a-vis
      cerebral digital subtraction angiography (DSA) in defining the morphological and
      haemodynamic characteristics of cerebral arteriovenous malformation (AVM).
      Methods Twenty-one patients (age range 10-46, mean 24.8 years) with clinical
      suspicion of AVM and three patients (age range 23-35, mean 24.3 years) with
      diagnosed AVM who were on follow-up underwent DSA and TR-CTA, on average 1.5 days
      apart. Three independent neuroradiologists analysed both studies in a blinded
      fashion based on the following parameters: AVM location, arterial feeder
      territories, venous drainage pattern, nidus flow characteristics, venous outflow
      obstruction, arterial feeder enlargement, external carotid artery feeder,
      location of aneurysm if any, leptomeningeal and transdural recruitment,
      neoangiogenesis, and pseudophlebitic pattern. Results The TR-CTA correctly
      demonstrated AVM in all 21 positive cases. It concordantly detected location
      (21/21), venous drainage pattern (21/21), nidus flow characteristics (21/21), and
      the venous outflow obstruction (9/9). However, discordance was seen in the
      demonstration of the arterial feeder (2/45) ( p = 0.49), arterial enlargement
      (13/17) ( p = 0.103), external carotid artery feeder (0/1), aneurysmal location
      (3/5) ( p = 0.40), leptomeningeal recruitment (1/3) ( p = 0.40), neoangiogenesis
      (0/4) ( p = 0.028) and in the pseudophlebitic pattern (2/5) ( p = 0.167)
      demonstration. Conclusions The results suggest that TR-CTA can provide the
      important features of cerebral AVM which are required in patient management.

PMID- 29366363
TI  - Orbital Granulomatosis With Polyangiitis Mimicking IgG4-Related Disease in a 12
      Year-Old Male.
AB  - Granulomatosis with polyangiitis is rare in children. We report a case of a 12
      year-old male who presented with new symptoms of left eyelid swelling and ptosis.
      Magnetic resonance imaging showed an enhancing orbital mass suspicious for a
      neoplasm. Excisional biopsy was performed. Microscopic examination revealed
      fibrovascular tissue with dense collagenous fibrosis and mixed inflammatory
      infiltrate that included many plasma cells. Many small and medium-sized blood
      vessels showed granulomatous and necrotizing vasculitis with disruption of the
      vessel walls and fibrinoid necrosis. Immunostain for IgG highlighted the numerous
      plasma cells, approximately 50% of which were positive for IgG4 immunostain. A
      diagnosis of granulomatosis with polyangiitis was suggested, with recommendation
      of serologic testing for anti-neutrophil cytoplasmic antibodies. Serum anti
      neutrophil cytoplasmic antibodies were borderline high with a cytoplasmic
      staining pattern. The patient improved with steroid and methotrexate therapy.
      Granulomatosis with polyangiitis can present as an orbital mass in up to 30% of
      children. It may be misdiagnosed as IgG4-related disease since the inflammatory
      background in both conditions may be rich in plasma cells with a high proportion
      of IgG4+ plasma cells, and accompanied by fibrosis and obliterated blood vessels.
      The differential diagnosis in this location should also include inflammatory
      pseudotumor and inflammatory myofibroblastic tumor. Knowledge of this unusual
      manifestation of granulomatosis with polyangiitis and its diagnostic pitfalls can
      facilitate early diagnosis and treatment.

PMID- 29366365
TI  - Early Predictors and Correlates of Communication Function in Children With
      Cerebral Palsy.
AB  - Birth characteristics and developmental milestones were evaluated as early
      predictors/correlates of communication in children with cerebral palsy. The
      hypothesis was that maternal report of child's age for vocal play and first words
      would predict current functional communication. A case series of 215 children, 2
      to 17 years (mean age = 8.2 years, SD = 3.9) with cerebral palsy was recruited
      from medical practices in 3 Michigan cities. Early developmental data were
      collected by maternal interview. The child's Communication Function
      Classification System (CFCS) level was obtained from parent. Predictors of less
      functional communication included gestational age >32 weeks, number of
      comorbidities, age of first words after age 24 months, and use of communication
      methods other than speech. Several birth characteristics and developmental
      language milestones were predictive of later communication performance for
      children with cerebral palsy. These characteristics and milestones should trigger
      referrals for communication evaluations, including speech, language, hearing,
      and/or augmentative and alternative communication.

PMID- 29366364
TI  - Contribution of angiotensinogen M235T and T174M gene variants and haplotypes to
      preeclampsia and its severity in (North African) Tunisians.
AB  - BACKGROUND: Preeclampsia (PE) is a pregnancy-associated hypertensive disorder and
      a leading cause of maternal and neonatal morbidity and mortality. While its
      pathogenesis remains ill defined, several candidate genes for PE have been
      identified, but results remain inconclusive. We investigated the association of
      the angiotensinogen ( AGT) gene variants M235T and T174M with PE, and we analyzed
      the contribution of both variants to the severity of PE. METHODS: This case
      control study enrolled 550 Tunisian pregnant women: 272 with PE, of whom 147
      presented with mild, and 125 with severe PE, along with 278 unrelated age- and
      ethnically matched control women. AGT genotyping was performed by polymerase
      chain reaction-restriction fragment length polymorphism. RESULTS: Significantly
      higher M235T minor allele frequency (MAF) was associated with increased risk of
      PE ( p < 0.001). Decreased frequency of heterozygous T174M genotype carriers were
      found in control women ( p = 0.015), suggesting a protective effect of this
      genotype (odds ratio (95% confidence interval) = 0.51 (0.29-0.89)). Two-locus
      haplotype analysis demonstrated MM and TT haplotypes to be negatively and
      positively associated with PE, respectively. MAF of M253T, but not T174M, was
      higher in the severe PE group, and carrying M235T or T174M minor allele was
      associated with increased body mass index ( p < 0.001) among unselected PE women.
      CONCLUSIONS: AGT M235T and T174M variants contribute to an increased risk of
      developing PE, and for M235T to PE severity.

PMID- 29366366
TI  - The salivary alpha amylase awakening response is related to over-commitment.
AB  - We assessed the relationship between physiological and psychological measures of
      workplace stress as measured by the effort-reward imbalance (ERI) model, with a
      seldom studied sample of owner-operator dairy farmers. Dairy farmers (N = 74)
      self-reported ERI, over-commitment (OC), dedication, and health then provided
      awakening saliva samples that were used to calculate the salivary alpha amylase
      awakening response (sAA-AR), cortisol awakening response (CAR), and salivary
      immunoglobulin A (sIgA) level. ERI, OC, and dedication levels were not related
      with sIgA or the CAR, but more over-committed farmers had a less pronounced sAA
      AR. OC was more associated than ERI with the physiological indicators of stress,
      potentially due to the owner-operator sample used in this investigation. The
      suitability of sAA as a viable physiological measure of autonomic nervous system
      activity has been debated, but our findings promote its inclusion in future
      occupational stress research.

PMID- 29366367
TI  - Re-thinking technology and its growing role in enabling patient empowerment.
AB  - The presence and increase of challenges to eHealth in today's society have begun
      to generate doubts about the capability of technology in patient empowerment,
      especially within the frameworks supporting empowerment. Through the review of
      existing frameworks and articulation of patient demands, weaknesses in the
      current application of technology to support empowerment are explored, and key
      constituents of a technology-driven framework for patient empowerment are
      determined. This article argues that existing usage of technology in the design,
      development and implementation of patient empowerment in the healthcare system,
      although well intentioned, is insufficiently constituted, primarily as a result
      of fragmentation. Systems theory concepts such as holism and iteration are
      considered vital in improving the role of technology in enabling patient
      empowerment.

PMID- 29366368
TI  - Correction to: Pop et al., Patency of uterine wall in pregnancies following
      assisted and spontaneous conception with antecedent laparoscopic and abdominal
      myomectomies - a difficult case and systematic review.

PMID- 29366369
TI  - Social and Cultural Barriers to Women's Participation in Pap Smear Screening
      Programs in Low- and Middle-Income Latin American and Caribbean Countries: An
      Integrative Review.
AB  - PURPOSE: Pap smear screening programs have been ineffective in reducing cervical
      cancer mortality in most Latin American and Caribbean countries, in part due to
      low screening rates. The purpose of this review was to analyze recent studies to
      identify demographic, social, and cultural factors influencing women's
      participation in Pap screening programs in Latin America and the Caribbean.
      DESIGN/METHOD: For this integrative review, cervical cancer screening in Latin
      America and the Caribbean was searched using PubMed, CINAHL, EMBASE, and PsycINFO
      databases. Findings/Results: Demographic barriers to screening were socioeconomic
      status, education, race/ethnicity, and geography. Social barriers included lack
      of uniformity in screening guidelines, lack of knowledge regarding cervical
      cancer, and lack of preventive culture. Cultural barriers were fear/embarrassment
      and gender roles. CONCLUSIONS: There are multilevel barriers to Pap smear
      utilization among women in Latin America and the Caribbean. IMPLICATIONS FOR
      PRACTICE: Findings highlight a need for health system engagement, promotion of
      preventive care, and community-generated educational programs and solutions.

PMID- 29366370
TI  - Holistic Wellness in Older Adulthood: Group Differences Based on Age and Mental
      Health.
AB  - PURPOSE: To understand how demographic variables and depression symptoms relate
      to the prevalence of wellness, resilience, and age perception within a sample of
      community-dwelling older adults. DESIGN: In all, 200 residents across 12 senior
      housing sites were surveyed. Research questions included the following: (1) Do
      group differences exist in wellness, resilience, and age perception based on age,
      sex, race, education, and depression symptoms? (2) Which profile of variables is
      most strongly associated with self-rated depression among older adults? METHOD:
      Multivariate analyses of variance were used to examine group differences. A
      discriminant analysis demonstrated which variables comprised the profile of
      individuals who ascribed to depression symptoms. FINDINGS: Younger respondents
      (i.e., age 55-70) had significantly lower levels of wellness (eta2 = .034) and
      resilience (eta2 = .052). Respondents suffering from depression symptoms had
      lower levels of wellness (eta2 = .155), resilience (eta2 = .163), and positive
      age perception (eta2 = .067) and higher rates of negative age perception (eta2 =
      .052). The discriminant analysis correctly categorized 75.3% of the cases related
      to depression symptoms, and resilience and certain forms of wellness were most
      relevant. CONCLUSIONS: The current study sheds light into within-group
      differences in wellness, resilience, and age perception that depend on variables
      such as age and depression.

PMID- 29366371
TI  - The neuropsychological rehabilitation of visual agnosia and Balint's syndrome.
AB  - Visual agnosia and Balint's syndrome are complex neurological disorders of the
      higher visual system that can have a remarkable impact on individuals' lives.
      Rehabilitation of these individuals is important to enable participation in
      everyday activities despite the impairment. However, the literature about the
      rehabilitation of these disorders is virtually silent. Therefore, the aim of this
      systematic review is to give an overview of available literature describing
      treatment approaches and their effectiveness with regard to these disorders. The
      search engines Psychinfo, Amed, and Medline were used, resulting in 22 articles
      meeting the criteria for inclusion. Only articles describing acquired disorders
      were considered. These articles revealed that there is some information available
      on the major subtypes of visual agnosia as well as on Balint's syndrome which
      practising clinicians can consult for guidance. With regard to the type of
      rehabilitation, compensatory strategies have proven to be beneficial in most of
      the cases. Restorative training on the other hand has produced mixed results.
      Concluding, although still scarce, a scientific foundation about the
      rehabilitation of visual agnosia and Balint's syndrome is evolving. The available
      approaches give valuable information that can be built upon in the future.

PMID- 29366372
TI  - The role of teriparatide in tuberosity healing after reverse shoulder
      arthroplasty in complex proximal humeral fragility fracture.
AB  - INTRODUCTION: Tuberosity healing is known to be one of the factors that increase
      functional outcome in Reverse Total Shoulder Arthroplasty (rTSA). In fragility
      fractures, tuberosity healing is difficult to be achieved. The fragment stability
      and bone-forming agent application become strategies to overcome this problem.
      The purpose of this study was to evaluate the benefit of teriparatide application
      to promote tuberosity union in rTSA on four-part proximal humeral fractures to
      achieve better functional outcome. METHODS: A retrospective study of a
      prospectively collected shoulder arthroplasty medical record was performed.
      Eleven patients were included in this analysis and consisted of two groups,
      teriparatide and no-teriparatide groups. Patients were evaluated on the range of
      motions and clinical outcome using the American Shoulder Elbow Surgeon (ASES)
      Shoulder Score and X-ray to determine tuberosity union. The group differences
      were analyzed by t-test or Mann-Whitney U test with SPSS version 20.0 for
      Windows. RESULTS: The statistical analysis revealed no significant differences in
      mean age in both the groups. There were significant differences between
      teriparatide and no-teriparatide groups in external rotation (29.5 degrees  vs.
      7.5 degrees ; p = 0.004), external rotation in 90 degrees  abduction (55 degrees 
      vs. 12.5 degrees ; p < 0.020), forward flexion (120 degrees  vs. 105 degrees ; p
      = 0.002) range of motions, and ASES (84.5 vs. 74.6; p = 0.019). We found clinical
      difference between teriparatide and no-teriparatide groups in time to achieve the
      initial callus (33 +/- 18.3 days vs. 150 +/- 42.4 days) and tuberosity
      consolidation (165.8 +/- 70.3 days vs. 315 +/- 106.1 days). CONCLUSIONS:
      Teriparatide administration supports tuberosity repair results in a high
      tuberosity healing rate with restoration of external rotation after rTSA in acute
      complex proximal humeral fractures.

PMID- 29366373
TI  - Corrigendum.
AB  - McElroy M and Keshmiri A, Impact of using conventional inlet/outlet boundary
      conditions on haemodynamic metrics in a subject-specific rabbit aorta, Proc
      IMechE, Part H: Journal of Engineering in Medicine, first published on March 25,
      2017, DOI: 10.1177/0954411917699237 Following OnlineFirst publication of the
      article, the authors informed SAGE of an error in the transient velocity inlet
      profile which had been defined inaccurately due to a human error in the
      interpretation of clinical data in the literature. As a result of this error in
      boundary conditions, some of the results of transient flow computations were
      incorrect. A watermarked version of the first publication of the article (as
      first published on March 25, 2017) is attached for reference in the PDF version
      of this corrigendum. The authors have revised and corrected their article. The
      revised version of the article has been accepted following peer review and
      replaces the article first published on March 25, 2017. Date received: 8 August
      2017; accepted: 30 November 2017 (Revised version) Date received: 29 March 2016;
      accepted: 21 February 2017 (Original version) The correct and citable version of
      the article is accessible at the following DOI: 10.1177/0954411917699237.

PMID- 29366374
TI  - Poststroke Depressive Symptoms Are Associated With Increased Oxidative
      Deoxyribonucleic Acid Damage.
AB  - Poststroke depression is independently associated with poor health outcomes, such
      as increased mortality, disability, anxiety, and lower quality of life.
      Identifying the potential biomarkers and detailed mechanisms of poststroke
      depression may improve the effectiveness of therapeutic intervention. In this
      cross-sectional study, the authors recruited patients with subacute ischemic
      stroke who were consecutively admitted for neurorehabilitation. Depression was
      assessed with the Patient Health Questionnaire-9 (PHQ-9), with a cutoff based on
      a summed-items score of 10. Polysomnography and laboratory tests for oxidative
      stress and inflammation were arranged. In total, 139 patients (97 men [69.8%] and
      42 women [30.2%]; mean age: 63.2 years [+/-13.4]) with recent ischemic stroke
      were recruited and divided into two groups based on their depressive symptoms.
      Body mass index (BMI), the Barthel Index, percentage of antidepressant usage, and
      percentage of rapid eye movement (REM) sleep differed significantly between the
      two groups. The PHQ-9 score was significantly correlated with the levels of total
      antioxidant capacity, C-reactive protein, and urinary 8-hydroxy-2'-deoxyguanosine
      (8-OHdG). Urinary 8-OHdG, a marker of oxidative stress to DNA, remained
      significantly and positively correlated with PHQ-9 scores after adjusting for
      BMI, sleep-onset latency, Barthel Index, mean oxyhemoglobin saturation, age,
      antidepressant usage, and percentage of REM sleep by using multivariate linear
      regression. Depressive symptoms were related to increased oxidative DNA damage in
      patients with subacute ischemic stroke. Urinary 8-OHdG may serve as a potential
      biomarker for poststroke depression. Further longitudinal studies are needed to
      elucidate the causal relationship between poststroke depression and elevated
      oxidative stress level.

PMID- 29366375
TI  - Patient- and Technician-Oriented Attitudes Toward Transcranial Magnetic
      Stimulation Devices.
AB  - Four transcranial magnetic stimulation (TMS) devices are currently approved for
      use in treatment-resistant depression. The authors present the first data-driven
      study examining the patient- and technician-experience using three of these
      distinct devices. A retrospective survey design with both patient and technician
      arms was utilized. The study population included patients who received TMS for
      treatment-resistant depression at the Berenson Allen Center for Noninvasive Brain
      Stimulation for the first time between 2013 and 2016 and technicians who worked
      in the program from 2009 to 2017. Statistical analysis included t tests and
      analyses of variance to assess differences between and across the multiple
      groups, respectively. Patients treated with the NeuroStar device reported greater
      confidence that the treatment was being performed correctly compared with those
      treated with the Magstim device. Conversely, with regard to tolerability,
      patients treated with the Magstim device reported less pain in the last week and
      less pain on average compared with those treated with the NeuroStar device. On
      average, technicians reported feeling that both the Magstim and NeuroStar devices
      were significantly easier to use than the Brainsway Deep TMS H-Coil device.
      Additionally, they found the former two devices to be more reliable and better
      tolerated. Furthermore, the technicians reported greater confidence in the
      Magstim and NeuroStar devices compared with the Brainsway Deep TMS H-Coil device
      and indicated that they would be more likely to recommend the two former devices
      to other treatment centers.

PMID- 29366376
TI  - Do primary care placements influence career choice: What is the evidence?
AB  - BACKGROUND: The NHS is struggling with GP recruitment. The Health Education
      England (HEE) Wass Report (By Choice not by Chance), among its recommendations to
      boost GP numbers, highlighted undergraduate (UG) GP placement experience as an
      important influence on future career choice. Aim To explore the UG influences on
      GP career choice. METHODS: Two junior doctors produced a pragmatic rapid
      appraisal of the literature on the UG influences on GP career choice for the Wass
      Report. The search strategy was supported by librarians and focused on rapidly
      accessing and summarising relevant literature. Databases searched, including
      Medline, EMBASE, HMIC & grey literature, revealed 294 items. Data extraction and
      synthesis was pragmatic. RESULTS: The international evidence suggests that UG GP
      experience can positively influence students towards a primary care career.
      Longitudinal placements are more influential than traditional blocks. UK
      literature is limited, but there are consistencies with the international
      evidence. The relevant studies identified are observational with risk of bias,
      but this is unavoidable within this research context. DISCUSSION: The
      implications of these results for medical school curricula are discussed with
      particular reference to Government plans to expand medical student numbers and
      establish new medical schools with explicit aims to produce more GPs.

PMID- 29366377
TI  - Pulse Width Does Not Influence the Gains Achieved With Neuromuscular Electrical
      Stimulation in People With Multiple Sclerosis: Double-Blind, Randomized Trial.
AB  - BACKGROUND: Multiple sclerosis (MS) eventually compromises the walking ability of
      most individuals burdened with the disease. Treatment with neuromuscular
      electrical stimulation (NMES) can restore some functional abilities in persons
      with MS, but its effectiveness may depend on stimulus-pulse duration. OBJECTIVE:
      To compare the effects of a 6-week intervention with narrow- or wide-pulse NMES
      on walking performance, neuromuscular function, and disability status of persons
      with relapsing-remitting MS. METHODS: Individuals with MS (52.6 +/- 7.4 years)
      were randomly assigned to either the narrow-pulse (n = 13) or wide-pulse (n = 14)
      group. The NMES intervention was performed on the dorsiflexor and plantar flexor
      muscles of both legs (10 minutes each muscle, 4 s on and 12 s off) at a tolerable
      level for 18 sessions across 6 weeks. Outcomes were obtained before (week 0) and
      after (week 7) the intervention and 4 weeks later (week 11). RESULTS: There was
      no influence of stimulus-pulse duration on the outcomes ( P > .05); thus, the
      data were collapsed across groups. The NMES intervention improved ( P < .05) gait
      speed and walking endurance, dorsiflexor strength in the more-affected leg,
      plantar flexor strength in the less-affected leg, force control for plantar
      flexors in the less-affected leg, and self-reported levels of fatigue and walking
      limitations. CONCLUSION: There was no influence of stimulus-pulse duration on the
      primary outcomes (gait speed and walking endurance). The 6-week NMES intervention
      applied to the lower leg muscles of persons with mild to moderate levels of
      disability can improve their walking performance and provide some symptom relief.

PMID- 29366378
TI  - Development and validation of the Patient Benefit Index for peripheral arterial
      disease.

PMID- 29366379
TI  - Pharmacy Student Monitoring of Direct Oral Anticoagulants.
AB  - BACKGROUND: Best practice recommendations are lacking. Thus far, literature has
      described pharmacist-led DOAC monitoring. OBJECTIVE: The purpose of this study is
      to describe a DOAC monitoring program involving pharmacy students. METHODS: This
      was an observational analysis of a quality improvement initiative. A clinical
      pharmacist preceptor identified clinic patients taking DOACs by running a report
      using the electronic medical record. Pharmacy students conducted chart reviews,
      called pharmacies for 6-month refill histories, and interviewed and educated
      patients. Findings were communicated to the care team and interventions were
      performed as applicable with the preceptor. RESULTS: Of 90 patients included, the
      mean age was 63 years, 54% were female, and 65.6% were black or African American.
      Rivaroxaban and apixaban were used most commonly. Sixty-two percent of DOACs were
      prescribed for atrial fibrillation/flutter, while 32.2% for venous
      thromboembolism. The mean MPR was 77.1%, with 27.7% of patients having an MPR
      <=60%. Of the 136 student-led interventions, 25.2% involved medication access,
      24.4% adherence education, 20.7% processing refills, 14.8% laboratory monitoring
      recommendations, 8.9% switching or recommending switching to another
      anticoagulant, and 4.4% stopping a nonsteroidal anti-inflammatory drug or
      aspirin. CONCLUSION: Pharmacy students can help to ensure medication safety and
      effective use of DOACs.

PMID- 29366380
TI  - Oral solution of fructose promotes SREBP-1c high-expression in the hypothalamus
      of Wistar rats.
AB  - OBJECTIVE: We evaluate whether the consumption of fructose for 8 weeks affects
      enzymes and transcription factors of the lipogenic and inflammatory pathways in
      the hypothalamus of Wistar rats. METHODS: At 30 days, the animals were divided
      into groups: Control (C) and Fructose (F) and maintained with free access to feed
      and filtered water (C) or aqueous solution of purified fructose at 20% (F). RT
      PCR and Western blotting were performed for the target genes and proteins.
      RESULTS: In F group, results showed a lower feed intake, an increase in glycemia
      (146.20 +/- 6.09 vs. 102.32 +/- 4.58; n: 9) and triacylglycerol (F: 191.65 +/-
      13.51 vs. C: 131.69 +/- 6.49; n: 9) and there was no difference in water and
      energy consumption. We identified a higher content of acetyl-CoA carboxylase
      (ACC) (F: 133.93 +/- 5.58 vs. C: 100 +/- 0.0; n: 9-10) and NFkappaB (F: 125.5 +/-
      8.85 vs. C: 100 +/- 0; n: 14) in group F, whereas fatty acid synthase (FAS) was
      lower (F: 85.90 +/- 4.81 vs. C: 100 +/- 0.0; n: 4-6). SREBP-1c gene expression
      was higher in F vs. C group (F: 4.08 +/- 0.44 vs. C: 1.13 +/- 0.15; n: 5-6),
      although we did not found difference between groups in the gene expression for
      ACC, SREBP-2, and NFkappaB. DISCUSSION: Dietary fructose can change important
      lipogenic and inflammatory factors in the hypothalamus of rats and it leads to
      regulation of transcription factors before changes in body mass are evident.

PMID- 29366381
TI  - An Atypical Rett Syndrome Phenotype Due to a Novel Missense Mutation in CACNA1A.
AB  - BACKGROUND: Some typical and atypical Rett syndrome patients lack known genetic
      mutations. Mutations in the P/Q type calcium channel CACNA1A have been implicated
      in epileptic encephalopathy, familial hemiplegic migraine, episodic ataxia 2, and
      spinocerebellar ataxia 6, but not Rett syndrome. Patient Description: The authors
      describe a female patient with developmental regression and a de novo, likely
      pathogenic mutation in CACNA1A who meets 3 of 4 main criteria (stereotypic hand
      movements, loss of purposeful hand movements, gait disturbance), and 6 of 11
      supportive criteria (impaired sleep, abnormal tone, vasomotor disturbance,
      scoliosis, growth retardation, and screaming spells) for atypical Rett syndrome.
      Furthermore, she resembles the early seizure variant of Rett syndrome.
      Previously, 3 children with similar CACNA1A mutations have been reported, but a
      Rett syndrome phenotype has not been described. CONCLUSION: CACNA1A mutations
      should be considered in children presenting with an atypical Rett syndrome
      phenotype, specifically, the early seizure variant.

PMID- 29366383
TI  - The MRCGP Clinical Skills Assessment: an integrative review of evidence.
AB  - Background Successful completion of all three components of the Membership of the
      Royal College of General Practitioners UK (MRCGP) is required for a doctor to
      practise independently as a general practitioner (GP). One component, the
      Clinical Skills Assessment (CSA), is a high fidelity, high stakes examination
      designed to provide an objective external assessment of clinical skills. Aim The
      aim of this integrative review was to identify, critically appraise and
      synthesise published empirical evidence on the CSA to identify areas for further
      inquiry or future collaboration. Design and setting An integrative review of
      empirical literature focused on the MRCGP CSA. Method A search strategy was
      developed to conduct an integrative review of empirical published literature. The
      quality of studies was assessed using the Mixed Methods Appraisal Tool (MMAT).
      Results 11 of the 31 records reviewed were included. Studies were heterogeneous
      looking at the use of simulated patients, child actors and mock CSAs. Variables
      contributing to performance on the CSA, with a particular emphasis on the
      International Medical Graduate, were identified. Conclusion A small pool of
      published evidence regarding the CSA exists, focused on factors influencing CSA
      performance. Future research could explore the effectiveness of interventions to
      improve performance on the CSA and use robust measures to consider candidates'
      experience of the CSA.

PMID- 29366382
TI  - The research contributions of predominantly North American Family Medicine
      educators to medical learner feedback: a descriptive analysis following a scoping
      review.
AB  - BACKGROUND AND OBJECTIVES: In 2016, we performed a scoping review as a means of
      mapping what is known in the literature about feedback to medical learners. In
      this descriptive analysis, we explore a subset of the results to assess the
      contributions of predominantly North American family medicine educators to the
      feedback literature. METHODS: Nineteen articles extracted from our original
      scoping review plus six articles identified from an additional search of the
      journal Family Medicine are described in-depth. RESULTS: The proportion of
      articles involving family medicine educators identified in our scoping review is
      small (n=19/650, 3%) and the total remains low (25) after including additional
      articles (n=6) from a Family Medicine search. They encompass a broad range of
      feedback methods and content areas. They primarily originated in the United
      States (n=19) and Canada (n=3) within Family Medicine Departments (n=20) and
      encompass a variety of scientific and educational research methodologies.
      CONCLUSIONS: The contributions of predominantly North American Family Medicine
      educators to the literature on feedback to learners are sparse in number and
      employ a variety of focus areas and methodological approaches. More studies are
      needed to assess for areas of education research where family physicians could
      make valuable contributions.

PMID- 29366385
TI  - Exploring the process of change in emotion-focused therapy for social anxiety.
AB  - OBJECTIVE: This study examined purported change mechanisms in emotion-focused
      therapy for social anxiety disorder. METHODS: The sample included nine clients
      who had participated in a multiple-baseline case study trial examining the
      efficacy of emotion-focused therapy for social anxiety disorder (SAD). Multilevel
      analyses were conducted to examine the trajectories of emotions over the course
      of treatment, and whether primary adaptive emotions in a given session predicted
      levels of SAD symptoms, self-criticism, and self-reassurance over the course of
      the following week. RESULTS: Findings showed a significant decrease in shame, and
      a marginally significant increase in assertive anger, over the course of
      treatment. Adaptive sadness/grief in a given session predicted less fear of
      negative evaluation over the course of the following week. Shame in a given
      session predicted higher levels of inadequate-self over the course of the
      following week. Finally, shame, and to a lesser degree assertive anger, in a
      given session predicted reassurance of self over the course of the following
      week. Neither assertive anger nor adaptive sadness/grief in a given session
      predicted levels of self-criticism over the course of the following week.
      CONCLUSIONS: These findings lend partial preliminary support for the therapeutic
      role of evoking and processing adaptive sadness/grief and assertive anger in the
      treatment of SAD.

PMID- 29366384
TI  - Representation of Nursing Scientists from German-speaking countries in High
      Impact Journals. A bibliometric publication analysis
AB  - Background: The frequency of publications by nursing scientists from the German
      speaking area in journals with a high impact factor is an indicator for
      participation of the discipline in the international discourse. Previous
      publication analyses focused on nursing science journals only and regularly found
      an underrepresentation of experimental studies and clinical topics. Aim: To
      identify and analyse the number of publications by nursing scientists from
      Germany, Austria and German-speaking Switzerland in international high impact
      journals. Method: The Journal Citation Reports were used to identify nursing
      relevant categories of journals in which the highest 10 % of the years 2010 to
      2014 were selected according to the 5-year Impact Factor. Inclusion of
      publications and data extraction were carried out by two independent persons.
      Results: 106939 publications from 126 journals were screened; 100 publications
      were identified with 229 contributions by 114 nursing scientists. 42 % of studies
      are observational and 11 % are experimental. The majority of studies are
      clinically oriented (55 %). More than 50 % have been published in the past two
      years. Conclusions: The number of publications by nursing scientists from the
      German-speaking countries in High Impact Journals is low. There is an increase
      throughout the observation period. In opposite to former analyses a higher
      proportion of clinical research has been found.

PMID- 29366386
TI  - The Use Of The Gore(r) Hybrid Vascular Graft For Treatment Of Complex Iliofemoral
      Revascularization Procedures.
AB  - PURPOSE: To describe the uses and advantages of hybrid vascular grafts (HVGs) for
      complex iliofemoral revascularization procedures. CASE REPORT: We report 3 cases
      of iliofemoral occlusions repaired with the Gore HVG, used as an alternative
      technique to standardized common femoral artery (CFA) endarterectomy associated
      with iliac stenting or open repair. The indication in each of the 3 cases was
      different: In the first case, there was an absent CFA secondary to a mycotic
      pseudoaneurysm, in the second case, an iatrogenic lesion of the posterior wall of
      the CFA during the intervention was performed, and in the third case, the
      indication was because of thrombosis of a previous iliofemoral revascularization
      procedure. CONCLUSION: Although we only present 3 cases, the Gore HVG can be
      useful for complex iliofemoral revascularizations, serving as an alternative to
      standardized CFA endarterectomy plus iliac stenting in cases where there is a
      damaged or absent CFA, especially in high-surgical risk patients.

PMID- 29366387
TI  - Special Issue: Monitoring Health Determinants with an Equity Focus.

PMID- 29366389
TI  - Editorial.

PMID- 29366390
TI  - Postoperative daily living activities of geriatric patients administered general
      or spinal anesthesia for hip fracture surgery: A retrospective cohort study.
AB  - PURPOSE: Maintaining independence after hip fracture repair is important for
      geriatric patients and general welfare. We investigated the effects of anesthetic
      methods on postoperative activities of daily living (ADLs) following hip fracture
      surgery in elderly patients. METHODS: The medical records of 12,342 patients aged
      >=65 years who underwent typical surgeries for hip fracture using either general
      anesthesia or spinal anesthesia were reviewed. To adjust for baseline differences
      and minimize selection bias for the chosen method of anesthesia, patients were
      matched by propensity scores. Factors affecting the deterioration in ADLs during
      hospital stay were also investigated in all subjects using a multivariate
      logistic regression analysis. Eating, grooming, toileting, bathing, and walking
      were selected as the ADL parameters, as they are considered important for an
      independent life. RESULTS: Of the 12,342 patients, 6918 (56.1%) received general
      anesthesia and 5424 (43.9%) received spinal anesthesia. After the propensity
      score matching, the anesthesia types were not associated with ADL scores except
      toileting at discharge. Results from the multivariate logistic regression
      analysis showed that the types of anesthesia were not associated with
      deterioration in ADL scores. Advanced age, male sex, high Charlson Comorbidity
      Index scores, psychiatric disease, no administration of nonsteroidal anti
      inflammatory drugs, and short length of hospital stay were associated with
      deterioration in ADL scores. CONCLUSION: The anesthesia types were not associated
      with ADL dependency except toileting at discharge. Spinal anesthesia adversely
      affected toilet use at hospital discharge. However, anesthesia types were not
      factors that affected deterioration in ADL during hospital stay in elderly
      patients who underwent hip fracture surgery.

PMID- 29366391
TI  - Fracture lines and comminution zones in OTA/AO type 23C3 distal radius fractures:
      The distal radius map.
AB  - OBJECTIVE: This study was designed to define fracture lines and comminution zones
      in OTA/AO 23C3 distal radius fractures from axial computed tomography (CT) images
      that would influence surgical planning, development of new classifications, and
      possible implant designs. METHODS: Thirty-four consecutive OTA/AO 23C3 fractures
      treated by a single surgeon between January 2014 and December 2014 were analyzed.
      For each fracture, maps of the fracture lines and zones of comminution were
      drawn. Each map was digitized and graphically superimposed to create a
      compilation of fracture lines and zones of comminution. Based on this
      compilation, major and minor fracture lines were identified and fracture patterns
      were defined. RESULTS: All major fracture lines were distributed in the central
      region of the radius distal articular surface. There is a recurrent fracture
      pattern with a comminution zone including the scaphoid and lunate fossa; Lister's
      tubercle; and ulnar, volar, and radial zones. CONCLUSION: It is important for the
      practicing surgeon to understand these four main fragments. Knowledge of this
      constant pattern should influence the development of new classifications and
      possible implant designs.

PMID- 29366388
TI  - Burden of cardiovascular disease across 29 countries and GPs' decision to treat
      hypertension in oldest-old.
AB  - OBJECTIVES: We previously found large variations in general practitioner (GP)
      hypertension treatment probability in oldest-old (>80 years) between countries.
      We wanted to explore whether differences in country-specific cardiovascular
      disease (CVD) burden and life expectancy could explain the differences. DESIGN:
      This is a survey study using case-vignettes of oldest-old patients with different
      comorbidities and blood pressure levels. An ecological multilevel model analysis
      was performed. SETTING: GP respondents from European General Practice Research
      Network (EGPRN) countries, Brazil and New Zeeland. SUBJECTS: This study included
      2543 GPs from 29 countries. MAIN OUTCOME MEASURES: GP treatment probability to
      start or not start antihypertensive treatment based on responses to case
      vignettes; either low (<50% started treatment) or high (>=50% started treatment).
      CVD burden is defined as ratio of disability-adjusted life years (DALYs) lost due
      to ischemic heart disease and/or stroke and total DALYs lost per country; life
      expectancy at age 60 and prevalence of oldest-old per country. RESULTS: Of 1947
      GPs (76%) responding to all vignettes, 787 (40%) scored high treatment
      probability and 1160 (60%) scored low. GPs in high CVD burden countries had
      higher odds of treatment probability (OR 3.70; 95% confidence interval (CI) 3.00
      4.57); in countries with low life expectancy at 60, CVD was associated with high
      treatment probability (OR 2.18, 95% CI 1.12-4.25); but not in countries with high
      life expectancy (OR 1.06, 95% CI 0.56-1.98). CONCLUSIONS: GPs' choice to
      treat/not treat hypertension in oldest-old was explained by differences in
      country-specific health characteristics. GPs in countries with high CVD burden
      and low life expectancy at age 60 were most likely to treat hypertension in
      oldest-old. Key Points  * General practitioners (GPs) are in a clinical dilemma
      when deciding whether (or not) to treat hypertension in the oldest-old (>80 years
      of age).  * In this study including 1947 GPs from 29 countries, we found that a
      high country-specific cardiovascular disease (CVD) burden (i.e. myocardial
      infarction and/or stroke) was associated with a higher GP treatment probability
      in patients aged >80 years.  * However, the association was modified by country
      specific life expectancy at age 60. While there was a positive association for
      GPs in countries with a low life expectancy at age 60, there was no association
      in countries with a high life expectancy at age 60.  * These findings help
      explaining some of the large variation seen in the decision as to whether or not
      to treat hypertension in the oldest-old.

PMID- 29366392
TI  - Long-term clinical outcome of two-stage revision surgery for infected hip
      arthroplasty using cement spacer: Culture negative versus culture positive.
AB  - INTRODUCTION: Periprosthetic joint infection (PJI) is a terrible complication
      after hip arthroplasty. Clinical feature of culture-negative PJI (CN-PJI) has not
      been well studied till now. In our study, we retrospectively analyzed long-term
      clinical results after two-stage revision arthroplasty using an antibiotic
      impregnated cement spacer for CN-PJI. The purpose of this study is to investigate
      the clinical features and prognosis of CN-PJI after hip arthroplasty and to
      compare these with those of culture-positive PJI (CP-PJI). METHODS: We
      retrospectively reviewed 15 CN-PJI cases and 70 CP-PJI cases following hip
      arthroplasty. The average follow-up period was 7.4 years (5-11.7 years). The
      demographics, laboratory findings, the time interval between antibiotic
      impregnated cement spacer insertion and revision arthroplasty, and recurrence of
      infection were analyzed. RESULTS: The CN-PJI group showed a significantly higher
      incidence of prior antibiotic use ( p = 0.004) and lower serum C-reactive protein
      (CRP) level ( p = 0.001) than the CP-PJI group. Normalized time interval of CRP
      level in CN-PJI was shorter than that of CP-PJI group. The mean interval time for
      two-stage exchange arthroplasty was also significantly lower ( p = 0.049) in the
      CN-PJI group than the CP-PJI group. There was no case of treatment failure or
      major complication in CN-PJI group. CONCLUSION: The CN-PJI group after total hip
      arthroplasty could be treated successfully by two-stage exchange arthroplasty
      without any complications. Clinical course and prognosis of CN-PJI group was also
      better compared with that of CP-PJI group. Therefore, culture negativity of PJI
      cannot be always a poor prognostic factor for the treatment.

PMID- 29366393
TI  - Impact of changes in welfare legislation on the incidence of disability pension.
      A cohort study of construction workers.
AB  - AIMS: Study objectives were to investigate how changes in social insurance
      legislation influenced the incidence of disability pension. METHODS: The study
      included 295,636 male construction workers who attended health examinations
      between 1971 and 1993, aged 20-60 years and without previous disability pension.
      Via the Swedish National Insurance Agency national register we identified 66,046
      subjects who were granted disability pension up until 2010. The incidence rates
      were calculated and stratified according to age and diagnosis. RESULTS: The
      incidence rate of disability pension was fairly stable until the 1990s when large
      variations occurred, followed by a strong decreasing trend from the early 2000s
      to 2010. Trends in incidence rates, stratified by age and diagnosis, showed a
      consistent decrease in cardiovascular disease for all age groups. In subjects
      aged 30-49 years there was a high peak around 2003 for musculoskeletal diseases
      and psychiatric diseases. For the age group 50-59 years, musculoskeletal
      diagnosis, the most common cause of disability pension, had a sharp peak around
      1993 and then a decreasing trend. In the 60-64 age group, the incidence rate for
      psychiatric diagnosis was stable, while incidence rates for musculoskeletal
      diagnosis varied during the 1990s. CONCLUSIONS: There are considerable variations
      in the incidence rate of disability pension over time, with different patterns
      depending on age and diagnosis. Changes in social insurance legislation, as well
      as in administration processes, seem to influence the variation.

PMID- 29366394
TI  - Long-term sickness absence from work due to physical inactivity: A registry-based
      study.
AB  - AIMS: The aim of this study was to explore the relationship between leisure-time
      physical inactivity and long-term sickness absence in a representative sample of
      individuals aged 16-54 years, within the labour market and in good health. It was
      hypothesised that physically inactive individuals have a higher risk of long-term
      sickness absence and longer duration of sickness absence. METHODS: The study
      population was identified from the National Health and Morbidity Survey, 2010.
      Weekly data on long-term sickness absence were obtained from the National
      Register on Social Transfer Payments (the DREAM registry). The association of
      incidence and duration of long-term sickness absence with physical inactivity was
      explored using logistic and Poisson regression. Data were fitted to models with
      levels of physical activity, demographic, social and lifestyle characteristics as
      independent variables. A combined hurdle model was used to estimate the
      difference in mean number of absence weeks. RESULTS: Logistic regression showed
      that physically inactive individuals had a 27% higher incidence of long-term
      sickness absence compared with physically active individuals. The Poisson
      regression showed that long-term sickness absence was only slightly shorter (1
      week less) for moderately active individuals compared with inactive individuals.
      The hurdle model estimated longer absence periods for inactive individuals
      (additional 2.5 weeks) in comparison with moderately and highly active
      individuals. CONCLUSIONS: The study showed that physically inactive individuals
      have a higher incidence of long-term absence and that physically inactive
      individuals have longer periods with sickness absence than moderately and highly
      active individuals. When adjustments for social and health behaviour were
      included, the estimated associations became statistically insignificant.

PMID- 29366395
TI  - Validity and reliability of self-reported health indicators among women attending
      organized mammographic screening.
AB  - AIMS: Risk factors for breast cancer are often used for adjustment in
      epidemiological studies, including in the evaluation of early performance
      measures in mammographic screening. Information about risk factors among
      participants in the Norwegian Breast Cancer Screening Program has been collected
      since 2006. We aimed to examine the validity of self-reported history of breast
      cancer and mammographic screening, as well as the reliability of weight and
      height amongt women attending the program. METHODS: Information from a
      questionnaire handed in by participants in the program, 2006-2015, was linked to
      outcomes from the Cancer Registry of Norway. Sensitivity, specificity, and
      positive predictive values (PPV) were calculated for self-reported histories of
      breast cancer and screening. Results were stratified by five-year age groups and
      evaluated using the chi2 statistic. The reliability of self-reported weight and
      height were assessed using descriptive statistics, histograms, and mean
      differences. RESULTS: A total of 538,907 of 611,711 (88%) women attending the
      program during the study period returned at least one part of the questionnaire.
      The overall sensitivity, specificity, and PPV for breast cancer and mammography
      were 96.5%, 99.8%, and 81.3%; and 99.9%, 84.4%, and 97.6% respectively. The mean
      difference in self-reported weight was 0.35 kg and for height was -0.14 cm, over
      a period of up to 10 years. CONCLUSIONS: Norwegian women attending the screening
      program are reasonably accurate in self-reporting their breast cancer and
      mammography histories. On average, women consistently reported weight and height
      within one kg/cm.

PMID- 29366396
TI  - Assessment and Response to Intimate Partner Violence in Home Visitation: A
      Qualitative Needs Assessment With Home Visitors in a Statewide Program.
AB  - There is growing recognition that home visitation programs serving at-risk
      families may be an appropriate mechanism for detecting and reducing intimate
      partner violence (IPV). More research is needed about how home visitors assess
      and respond to IPV, especially in rural and underserved areas with unique social
      and geographic challenges. This study describes the qualitative, needs assessment
      phase of a larger mixed-methods evaluation of IPV assessment, referral processes,
      and safety planning with clients within a statewide home visitation program.
      Three focus groups were conducted with home visitors ( n = 16) in West Virginia's
      Home Visitation Program in May 2015. Home visitors represented four separate home
      visitation models and provided services across 12 of West Virginia's 55 counties.
      Guiding questions focused on home visitors' current protocol, experiences,
      barriers, and facilitators to (a) screening and assessment for IPV, (b) making
      referrals after disclosures of IPV, and (c) developing safety plans with IPV
      exposed clients. Barriers identified by home visitors included the nature of
      assessment tools, issues with service availability and access in rural areas, and
      lack of education and training surrounding safety planning. Facilitators included
      building relationships and trust with clients, providing anticipatory guidance
      when making referrals, and tailoring safety plans to clients' unique situations.
      Participants also expressed a critical need to develop procedures for assuring
      home visitor safety when supporting IPV-exposed clients. These qualitative data
      highlight issues surrounding the management of IPV in home visitation and have
      the potential to inform future enhancements to programs that are specifically
      tailored to the needs of rural, disadvantaged communities.

PMID- 29366397
TI  - Psychopathy and Intimate Partner Violence.
AB  - Several studies found that psychopathy is an important predictor of criminal
      behavior in general and of intimate partner violence in particular. However,
      these conclusions are often based on scales with less well-established validity,
      and some inconsistent results have emerged with regard to the contribution of
      specific psychopathic facets to intimate partner violence. In a sample of 152
      batterers from Portugal aged between 22 and 70 years old, we examined whether
      Psychopathy Checklist-Revised (PCL-R) total scores and the four facets (scored
      based on a semistructured interview and on file information) predicted the
      frequency of intimate partner violence. Two separate linear regression analyses
      were conducted controlling for criminal variables. PCL-R total scores positively
      predicted intimate partner violence frequency, above and beyond the criminal
      variables. As for the four facets, only the PCL-R affective facet held a
      significant effect in predicting intimate partner violence frequency after
      controlling for criminal variables. These results support the inclusion of
      psychopathy in risk assessments and treatment of perpetrators of intimate partner
      violence, particularly with regard to the affective deficits of the construct.

PMID- 29366398
TI  - Health and Health Needs of Children of Women Seeking Services for and Safety From
      Intimate Partner Violence.
AB  - Children exposed to intimate partner violence (IPV) are at increased risk for
      health problems. The moment that a mother seeks services for or safety from IPV
      may be a window of opportunity to offer needed health care for her children. The
      objective of the study is to describe the perceptions of child health conditions
      and needs among mothers seeking services for or safety from IPV, and to compare
      the results in shelter- versus community-based samples. A cross-sectional survey
      of women with at least one child of age 3 to 11 years seeking services at an
      urban YWCA, which supports a residential IPV shelter and a community-based family
      justice center, was done between fall 2013 and winter 2014. Child health
      conditions were captured using the Children With Special Health Care Needs survey
      and the Strengths and Difficulties Questionnaire. Prevalence of health conditions
      among IPV-exposed children was compared with population norms. Perceived child
      health and health needs in the residential versus community settings were
      compared. Women ( n = 48) completed surveys related to 91 children. Special
      health care needs (25%) and behavioral health (52%) problems were significantly
      higher in our sample than in general populations. Almost one quarter (24%) of
      children had a current need for general medical care and almost one half (44%)
      had a current need for behavioral health care. No significant differences in
      child health conditions or needs between residential and community settings were
      observed. These findings extend prior research describing the health problems
      faced by children exposed to IPV by describing maternal perceptions of child
      health and need for health care in a critical moment of seeking help for IPV.
      Community agencies may use this window of opportunity to support child health and
      household safety.

PMID- 29366399
TI  - Silent Victims in the Public Eye: Socially Vulnerable EU Citizens' Exposure to
      Crime and Its Consequences.
AB  - This study used thematic analysis to explore 28 socially vulnerable European
      Union (EU) citizens who support themselves by begging in public spaces in Malmo,
      Sweden, their exposure to crime, and the consequences of victimization. The
      analysis revolved around the following themes: daily harassment in public spaces,
      multiple motives for victimization, strategies to combat victimization, and
      consequences of victimization. The participants described that they lived in a
      constant state of stress, due to their marginalized life situation and a fear of
      becoming victimized in public spaces while begging. Study participants claimed
      that it was not their ethnicity but rather the activity of begging and their
      overall vulnerable life situation together with a label as "non-Swedish" that
      motivate offenders to commit attacks against them. The discussion concludes by
      presenting a number of policy implications.

PMID- 29366400
TI  - Use of computed tomography imaging during long-term follow-up of nine feline
      tuberculosis cases.
AB  - Case series summary Feline tuberculosis is an increasingly recognised potential
      zoonosis of cats. Treatment is challenging and prognosis can vary greatly between
      cases. Pulmonary infection requires extended courses of antibiotics, but
      methodologies for sensitively monitoring response to treatment are currently
      lacking. In this case series, we retrospectively examined the serial computed
      tomography (CT) findings in nine cats that had been diagnosed with tuberculosis.
      Changes in pathology (where applicable to tuberculosis) were correlated with the
      clinical presentation of each of the cats, the treatment protocol, and previous
      and contemporary diagnostic investigations. This study found that changes in CT
      findings during the medium- to long-term management of feline tuberculosis were
      highly variable between cats. The majority of cats had reduced pathology at re
      examination during anti-tuberculous therapy, but pathology only resolved in a
      minority of cases. In some cases recurrence of pathology detected by CT imaging
      preceded clinical deterioration, allowing for rapid therapeutic intervention.
      Relevance and novel information When considered in combination with clinical
      findings, CT studies can aid in decision making regarding tapering of antibiotic
      protocols, or reintroduction of therapy in cases of recurrence or reinfection.
      This series also highlights that, in some cases, persistent abnormalities can be
      detected by CT, so complete resolution of CT pathology should not always be a
      goal in the management of feline tuberculosis.

PMID- 29366403
TI  - Editorial.

PMID- 29366404
TI  - Editorial: Recent Development of Drug Delivery Systems for Improving
      Bioavailability and Pharmacokinetics.

PMID- 29366405
TI  - Therapy-Related Changes in the Serum Proteome Patterns of Early Stage Breast
      Cancer Patients with Different Outcomes.
AB  - Adjuvant chemo- and/or radiotherapy is applied in a majority of patients treated
      for early stage breast cancer, although only a small percentage of these
      individuals are at high risk of metastasis or recurrence. Hence, knowledge of the
      biomarkers associated with the risk of disease progression might facilitate the
      planning of an optimal therapy and protect many patients from the toxicity of
      unnecessary treatment. In this study, we characterized the serum proteome of
      patients diagnosed with early-stage breast cancer, exhibiting either no evidence
      of disease five years after the end of therapy or suffering from metastasis,
      relapse or a second cancer during the corresponding follow-up. Samples collected
      before treatment and one year after the end of therapy, when no clinical symptoms
      of a treatment failure was evidenced, were analyzed using two classical
      proteomics approaches: LC-MS/MS and 2D-PAGE. A total of 42 proteins with relative
      quantities that were significantly different between pre- and post-treatment
      samples were identified in either group of patients; however, the observed
      changes were more frequent in the treatment-failure group. Among the
      posttreatment samples, 30 proteins were upregulated, and 10 proteins were
      downregulated, while 11 proteins were upregulated, and eight proteins were
      downregulated in the control group. Moreover, several proteins exhibited
      different patterns of changes in both groups of patients. For example,
      haptoglobin expression increased in the treatment-failure group but decreased in
      the control group (this pattern of changes was confirmed using an immunoassay).
      Notably, proteins affected in posttreatment samples in either group of patients
      could be associated with different molecular and cellular functions, including
      angiogenesis, blood coagulation and wound healing in the treatment-failure group
      and cell adhesion and cell death in the control group.

PMID- 29366406
TI  - Preparation of Potent Leptin Receptor Antagonists and Their Therapeutic Use in
      Mouse Models of Uremic Cachexia and Kidney Fibrosis.
AB  - Leptin antagonists (L39A/D40A/F4lA mutants) of mouse, human, rat and ovine
      leptins were developed in our laboratory by rational mutagenesis, expressed in
      Escherichia coli, refolded and purified to homogeneity. Pegylation of these
      antagonists resulted in long-acting reagents suitable for in-vivo studies.
      Further selection of high-affinity leptin antagonists was achieved by random
      mutagenesis of the whole open reading frame followed by yeast- surface display;
      an additional mutation (D23L) increased their affinity toward leptin receptor 60
      fold. This superactive pegylated mouse leptin antagonist (PLA) exhibited a strong
      orexigenic effect, leading, in 10-14 days, to a 40% increase in body weight
      resulting mainly from obesity; this was reversed once PLA treatment was ceased.
      Cachexia is common in patients with Chronic Kidney Disease (CKD). Our studies
      suggested that leptin mediates cachexia by decreasing food intake while
      increasing energy consumption in CKD mice. We showed that PLA ameliorates CKD
      associated cachexia in mice. Leptin may also contribute to the development of
      muscle and renal fibrosis in CKD, serious complications associated with increased
      morbidity and mortality. Transforming growth factor (TGF)-beta signaling may be
      the most potent mediator of fibrogenesis in multiple organs, and leptin is a co
      activator of TGF-beta. Muscle fibrosis was evident in our CKD mice and PLA
      treatment significantly reduced the mRNA levels of TGF- beta1 and its downstream
      targets in their muscle and renal tissues. PLA may offer a novel therapeutic
      strategy for CKD-associated cachexia, muscle and renal fibrosis to improve CKD
      patients' survival and quality of life.

PMID- 29366407
TI  - The Emerging Therapeutic Landscape of Advanced Melanoma.
AB  - Melanoma is the deadliest form of skin cancer being responsible for 80% of skin
      cancer deaths. Furthermore, the incidence of metastatic melanoma has increased
      over the past three decades with a mortality rate that continues to rise faster
      than most of all other cancers. The last few years have witnessed an unparalleled
      change in treatment options for patients with metastatic melanoma by the
      development of new therapeutic strategies like targeted therapies and
      immunotherapies that highly improved the patient's prognosis. Despite the
      paradigm- shifting success of these novel treatments, their effectiveness is
      still limited by intrinsic or acquired resistance. The objective of this review
      is to provide an overview of the new available treatment modalities, criteria to
      select patients who might benefit from a specific therapy, mechanisms of innate
      and acquired resistance to these treatments and to discuss strategies to overcome
      drug resistance.

PMID- 29366409
TI  - A Phosphine-mediated Synthesis of 2,3,4,5-tetra-substituted N-hydroxypyrroles
      from alpha-oximino Ketones and Dialkyl Acetylenedicarboxylates Under Ionic Liquid
      Green-media.
AB  - BACKGROUND: The development of multicomponent reactions (MCRs) in the presence of
      task-specific ionic liquids (ILs), used not only as environmentally benign
      reaction media, but also as catalysts, is a new approach that meet with the
      requirements of sustainable chemistry. In recent years, the use of ionic liquids
      as a green media for organic synthesis has become a chief study area. This is due
      to their unique properties such as non-volatility, non-flammability, chemical and
      thermal stability, immiscibility with both organic compounds and water and
      recyclability. Ionic liquids are used as environmentally friendly solvents
      instead of hazardous organic solvents. OBJECTIVE: We report the condensation
      reaction between alpha-oximinoketone and dialkyl acetylene dicarboxylate in the
      presence of triphenylphosphine to afford substituted pyrroles under ionic liquid
      conditions in good yields. RESULT: Densely functionalized pyrroles was easily
      prepared from reaction of alpha-oximinoketones, dialkyl acetylene dicarboxylate
      in the presence of triphenylphosphine in a quantitative yield under ionic liquid
      conditions at room temperature. CONCLUSION: In conclusion, ionic liquids are
      indicated as a useful and novel reaction medium for the selective synthesis of
      functionalized pyrroles. This reaction medium can replace the use of hazardous
      organic solvents. Easy work-up, synthesis of polyfunctional compounds, decreased
      reaction time, having easily available-recyclable ionic liquids, and good to high
      yields are advantages of present method.

PMID- 29366408
TI  - A High-throughput Screening of a Chemical Compound Library in Ovarian Cancer Stem
      Cells.
AB  - BACKGROUND: Epithelial ovarian cancer has a poor prognosis, mostly due to its
      late diagnosis and the development of drug resistance after a first platinum
      based regimen. The presence of a specific population of "cancer stem cells" could
      be responsible of the relapse of the tumor and the development of resistance to
      therapy. For this reason, it would be important to specifically target this
      subpopulation of tumor cells in order to increase the response to therapy.
      METHOD: We screened a chemical compound library assembled during the COST CM1106
      action to search for compound classes active in targeting ovarian stem cells. We
      here report the results of the high-throughput screening assay in two ovarian
      cancer stem cells and the differentiated cells derived from them. RESULTS AND
      CONCLUSION: Interestingly, there were compounds active only on stem cells, only
      on differentiated cells, and compounds active on both cell populations. Even if
      these data need to be validated in ad hoc dose response cytotoxic experiments,
      the ongoing analysis of the compound structures will open up to mechanistic drug
      studies to select compounds able to improve the prognosis of ovarian cancer
      patients.

PMID- 29366410
TI  - One-pot Synthesis of Novel 2-pyrazolo-3-phenyl-1,3-thiazolidine-4-ones Using
      DSDABCOC as an Effective Media.
AB  - BACKGROUND: Thiazolidine compounds are known to show interesting pharmacological
      activity. In particular, they are used as antiseizure, fungicidal, anti
      bacterial, antitubercular, antiinflammatory, antiamoebic, anti-diabetic and local
      anesthetic agents. Some of these compounds have also shown antiparkinsonism,
      antioxidant, anticonvulsant, hypoglycemic and non-narcotic analgesic activities.
      On the other hand, pyrazoles have shown antibacterial, antitumor, antiviral,
      antifungal, anti-tubercular, antiparasitic, anesthetic, anti-diabetic, anti
      inflammatory, analgesic and insecticidal activities. In order to improve the
      pharmacological effects of thiazolidine-4-ones, new pyrazole derivatives have
      been synthesized. MATERIAL AND METHODS: A mixture of pyrazolcarbaldehydes,
      anilines, thioglycolic acid and DSDABCOC was stirred at room temperature for the
      required reaction times. The progress of the reaction was monitored by TLC
      (EtOAc: petroleum ether 1:3). After completion of the reaction as indicated by
      TLC, the ionic liquid was separated by extraction with 2*15 mL of water. The
      solid residue was separated by column chromatography. The product was
      recrystallized from EtOH. The pure products were collected in 82-92% yields.
      RESULTS: In continuation of our ongoing studies to synthesize heterocyclic and
      pharmaceutical compounds under mild and practical protocols, we wish to report
      herein our experimental results on the ultrasound promoted synthesis of 2
      pyrazolo-3-phenyl-1,3-thiazolidine-4-ones using various synthesized
      pyrazolecarbaldehydes, anilines and thioglycolic acid at room temperature. The
      results illustrated that ionic liquid DSDABCOC certainly improved the yield of
      the products and reduced the reaction time. CONCLUSION: In conclusion, we have
      developed an efficient and simple protocol for the synthesis of novel pyrazolo
      1,3-thiazolidine-4-ones using DSDABCOC as an ionic liquid. The easy workup
      together with the use of inexpensive, reusable and eco-friendly ionic liquid is
      the notable feature of this novel procedure. To the best of our knowledge, this
      is the first report of the synthesis of a new library of 1,3-thiazolidine-4-ones
      bearing a pyrazolyl moiety that enhances the biological activity under solvent
      free conditions.

PMID- 29366411
TI  - Effects of GHB On Psychomotor and Driving Performance.
AB  - BACKGROUND: Gamma-hydroxybutyrate (gamma-hydroxybutyrate or GHB) is a
      physiological compound of mammalians with specific receptors in central nervous
      system (CNS). Apart from an endogenous production, GHB is also an exogenous
      molecule found in pharmaceutical as well as in illicit formulations. Products
      manufactured and spread in these two fields, whose borders are all but strictly
      defined and traced, differ for the in vivo effects and for the potential of
      abuse. Illicit GHB gained public attention due to its use as a sexual assault
      facilitator. Notwithstanding its popularity, the effects on human performances,
      are still not completely understood and could be more complex than expected.
      Therefore, there is a real public safety concern regarding psychomotor functions
      and driving abilities due to GHB ingestion. OBJECTIVE: To provide an updated and
      complete review on the effects of GHB on psychomotor, cognitive and driving
      performance that may be useful for judiciary expert forensic evaluation of
      driving under the influence of GHB (GHB-DUI). METHOD: Experimental animal-based
      and human-based studies and case series or epidemiological studies regarding
      driving under influence of GHB (and its precursors) were reviewed using main
      scientific databases. RESULTS: The effects of GHB on cognitive, psychomotor and
      driving performance are dose-related in experimental studies. In real cases of
      driving under the influence of GHB, severe impairment is observed. In these
      cases, a wide range of blood GHB levels are found. Possible long-term effects are
      also reported. CONCLUSION: GHB causes cognitive and psychomotor impairment and
      risky driving behavior. Multiple aspects and variables are still waiting
      clarification, such as the harmful potential of illicit preparations, the effect
      of precursors and impairing dosages. GHB (and its precursors) must be considered
      a substantial personal and public risk even in the absence of a clear dose
      effects correlation.

PMID- 29366412
TI  - Adaptive Genetic Differentiation and Solar Radiation in Wild Emmer Wheat,
      Triticum dicoccoides.
AB  - BACKGROUND: Microgeographic studies of molecular markers could reveal the nature
      and dynamics of genetic diversity and the evolutionary driving forces shaping
      evolution. METHODS: The microclimatic genetic divergence of wild emmer wheat
      associated with solar radiation was investigated, in the present study, using
      multiple types of molecular markers including allozyme, amplified polymorphic DNA
      (RAPD), simple sequence repeat (SSR), and single nucleotide polymorphisms (SNP).
      The studies included two climatic microniches: (1) sunny between oak trees; and
      (2) shady under the canopies of oak trees. RESULTS: All four types of markers
      showed a similar microniche tendency of genetic variance, i.e., lower in the
      shady than in the sunny niche. Significant genetic divergence at some loci
      including allozyme, RAPD, SSR, and SNP was detected between the two climatic
      microniches, and also, the observed genetic differentiation is mainly due to
      natural selection. Based on different FST outlier detection algorithms, there
      were 21 candidate loci subjected to positive selection. Importantly, most of the
      identified candidate loci were mapped in the selection "hot spots" of wheat
      genome. CONCLUSION: The present work implies that microclimatic selection appears
      to play an important role either in the protein-coding region or in the non
      coding region of wheat genomes, and hence, highlights the evolutionary theory of
      natural selection.

PMID- 29366413
TI  - Myotropic Effects of Cholinergic Muscarinic Agonists and Antagonists in the
      Beetle Tenebrio molitor L.
AB  - BACKGROUND: In mammals, the cholinergic nervous system plays a crucial role in
      neuronal regulation of physiological processes. It acts on cells by two types of
      receptors - nicotinic and muscarinic receptors. Both signal transmission pathways
      also operate in the central and peripheral cholinergic nervous system of insects.
      METHOD: In our pharmacological experiments, we studied the effects of two
      muscarinic agonists (carbachol, pilocarpine) and two muscarinic antagonists
      (atropine, scopolamine) on the muscle contractile activity of visceral organs in
      the beetle, Tenebrio molitor. RESULTS: Both antagonists, when injected to
      haemolymph at concentration 10-5 M, caused delayed and prolonged cardioinhibitory
      effects on heart contractility in ortho- and antidromic phases of heart activity
      in T. molitor pupa what was observed as negative chrono- and inotropic effects.
      Agonist of muscarinic receptors - carbachol evoked opposite effect and increased
      contraction rate but only in antidromic phase. Pilocarpine, the second agonist
      induced weak negative chronotropic effects in the antiand orthodromic phases of
      heart activity. However, neither agonists had an effect on semi-isolated beetle
      heart in vitro. Only atropine at the highest tested concentrations slightly
      decreased the frequency of myocardial contractions. These suggest the regulation
      of heart activity by muscarinic system indirectly. The tested compounds also
      affected the contractility of the oviduct and hindgut, but the responses of these
      organs were varied and depended on the concentration of the applied compounds.
      CONCLUSION: These pharmacological experiments suggest the possible modulation of
      insect visceral muscle contractility by the cholinergic nervous system and
      indirectly indicate the presence of muscarinic receptor(s) in the visceral organs
      of the beetle T. molitor.

PMID- 29366414
TI  - The Acidophilic Kinases PLK2 and PLK3: Structure, Substrate Targeting and
      Inhibition.
AB  - PLK2 and PLK3 are two closely related acidophilic kinases belonging to the Polo
      like kinases (PLKs), a family of five members in mammals with a central role in
      cell cycle and related events. PLK1 is the most investigated enzyme from both
      physiological and pharmaceutical points of view, however, several specialized
      cellular functions of PLK2 and PLK3 have been recently discovered paving the way
      to deepened studies on their biological roles and their feasible selection as
      future therapeutic targets. Our review aims to provide a summarized view of the
      current knowledge regarding PLK2 and PLK3 kinases, including substrate
      specificity and signaling pathways directly affected by these kinases. Finally,
      an overview of PLK2 and PLK3 pharmacological regulation and perspectives in
      future achievements are proposed.

PMID- 29366416
TI  - Finasteride Topical Delivery Systems for Androgenetic Alopecia.
AB  - Androgenetic alopecia, generally recognized as male pattern baldness, is a
      gradually developing medical and physiological change, which is manifested by
      continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent
      anti-baldness compound that selectively and competitively inhibits the 5alpha
      reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of
      sexual disorders including decrease in libido, gynecomastia, erectile
      dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since,
      hair follicles widely home in 5alpha-reductase, topical formulations of
      finasteride in comparison to its oral formulations are expected to potentially
      reduce its systemic adverse effects. The analysis of literature has revealed some
      delivery systems developed for the enhanced and localized penetration of
      finasteride into the skin. These finasteride delivery systems include
      polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and
      niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim
      of this review article is to briefly amass all literature on topical delivery of
      finasteride to elaborate best dosage form, i.e. formulation having maximum
      permeation rate. This study will serve as a future perspective regarding topical
      delivery of finasteride. The literature analysis has exhibited that most of the
      previous investigators have used propylene glycol in their finasteride-loaded
      topical formulations, while poloxamer P407, monoolein, transcutol P and choline
      was used in few formulations. Moreover, among all drug delivery systems,
      finasteride liposomal gel system consisting of 2% methyl cellulose and gel system
      containing poloxamer P407 exhibited the highest flux with a value of 28.4 +/- 1.3
      ug/cm2h and 23.1 +/- 1.4 ug/cm2h, respectively. Several topical drug delivery
      techniques such as topical microneedles, aerosol foams, nanoemulsions,
      microsponges, and emulsifier free formulations, fullerenes, ointments, pastes,
      creams, gel and lotions are still to be worthy regarding finasteride topical
      delivery in future.

PMID- 29366415
TI  - Dosage and Passage Dependent Neuroprotective Effects of Exosomes Derived from Rat
      Bone Marrow Mesenchymal Stem Cells: An In Vitro Analysis.
AB  - BACKGROUND: Neurodegenerative diseases comprise a group of disorders for which no
      treatment is available till date. Stem cell based therapy offers great hope and
      promise. However, stem cell transplantation is associated with certain
      disadvantages like poor targeted migration, engraftment and survival of the
      transplanted cells. MATERIAL & METHOD: Exosomes, a type of extracellular membrane
      vesicle released by all cell types including stem cells, offer an alternative to
      stem cell transplantation. Exosome carry a wide array of biomolecules and are
      implicated in exhibiting substantial benefits in the repair/regeneration of the
      injured tissue. Thus, exosomes offer an alternative therapeutic approach as a
      substitute of cell transplantation. In order to utilize exosomes for therapeutic
      purpose, it is essential to evaluate the appropriate passage number and the
      dosage to avoid possible cytotoxic effects. Here, we isolated exosomes from
      different passages of rat bone marrow mesenchymal stem cells (BM-MSC) and
      analysed the neuroprotective potential of BM-MSC exosomes in an in vitro model of
      excitotoxicity. RESULT: Our results demonstrated that the exosomes isolated from
      early passage of rat BM-MSC exhibited more efficient neuroprotective potential as
      opposed to later passages derived exosomes. Furthermore, the neuroprotective
      efficacy of exosome is dosage dependent. i.e. the lower dosage of exosomes was
      found to be neuroprotective, whereas higher dosage of exosomes (from later
      passages) was found to be detrimental to neurons. The early passage derived
      exosomes protected neurons through anti-apoptotic, anti-necrotic and anti-oxidant
      mechanisms. CONCLUSION: Our study suggests that adult stem cells derived exosomes
      could be a potential therapeutic agent to confer neuroprotection in
      neurodegenerative diseases like Alzheimer's disease.

PMID- 29366417
TI  - Protective Effects of Magnesium Sulfate on Radiation Induced Brain Injury in
      Rats.
AB  - OBJECTIVES: The effect of magnesium sulfate on brain tissue of SD rats irradiated
      by 6MeV electron was investigated. METHODS: SD rats were divided into three
      groups: control group, irradiation (IR group) and irradiation treated with
      magnesium sulfate (IR+M group). After being anesthetized, the whole brains of IR
      group and IR+M group were exposed to 6 MeV electron radiation. IR+M group was
      i.p. injected with 10% magnesium sulfate (400 mg/kg) one day before radiation and
      three days and five days after radiation. And on the 1st, 3rd, 7th and 14th day
      after radiation, SD rats were euthanatized to take brain tissue for the detection
      of calcium, redox status and cell apoptosis, as well as the expression of NF
      kappaB and ICAM-1. RESULTS: The results indicated that magnesium treatment may
      alleviate the elevation of calcium and enhance redox status through increasing
      the activities of superoxide dimutase (SOD) and myeloperodase (MPO), and
      decreasing the concentration of malondialdehyde (MDA). Tunnel and
      immunohistochemistry assay suggested that treatment with magnesium decreased the
      apoptosis rate of brain cells and the expressions of caspase-3, respectively.
      Decline of the expression of NF-kappaB and ICAM-1 protein was observed after the
      treatment of magnesium. CONCLUSION: All the results demonstrated that magnesium
      may elicit protective effect against radiationinduced brain injury by reducing
      calcium overload, improving redox and inhibiting cell apoptosis. Moreover,
      magnesium significantly down-regulated the protein or mRNA levels of NF-kappaB
      and ICAM- 1. The findings may provide references for the application of magnesium
      in clinic for brain injury induced by radiation.

PMID- 29366418
TI  - Ayahuasca: Psychological And Physiologic Effects, Pharmacology And Potential Uses
      In Addiction And Mental Illness.
AB  - : Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is
      made from bark of the Banisteriopsis caapi vine (contains beta-carboline
      alkaloids) and leaves of the Psychotria viridis bush (supply the hallucinogen N,N
      dimethyltryptamine (DMT)). Originally used by indigenous shamans for the purposes
      of spirit communication, magical experiences, healing, and religious rituals,
      across several South American countries ayahuasca has been incorporated into folk
      medicine and spiritual healing, and several Brazilian churches use it routinely
      to foster spiritual experience. More recently it is being used in Europe and
      North America, not only for religious or healing reasons, but also for
      recreation. OBJECTIVE: To review ayahuasca's behavioral effects, possible adverse
      effects, proposed mechanisms of action and potential clinical uses in mental
      illness. METHOD: We searched Medline, in English, using the terms ayahuasca,
      dimethytryptamine, Banisteriopsis caapi, and Psychotria viridis and reviewed the
      relevant publications. RESULTS: The following aspects of ayahuasca are
      summarized: Political and legal factors; acute and chronic psychological effects;
      electrophysiological studies and imaging; physiological effects, safety and
      adverse effects; pharmacology; potential psychiatric uses. CONCLUSION: Many years
      of shamanic wisdom have indicated potential therapeutic uses for ayahuasca, and
      many present day studies suggest that it may be useful for treating various
      psychiatric disorders and addictions. The side effect profile appears to be
      relatively mild, but more detailed studies need to be done. Several prominent
      researchers feel that government regulations with regard to ayahuasca should be
      relaxed so that it could be provided more readily to recognized credible
      researchers to conduct comprehensive clinical trials.

PMID- 29366419
TI  - Efficacy of Supplementation with Iron Sulfate Compared to Iron Bisglycinate
      Chelate in Preterm Infants.
AB  - BACKGROUND: Strategies to prevent anaemia in preterm infants include drawing
      fewer blood samples, the use of recombinant human erythropoietin and iron
      supplementation. Although iron sulfate is the most commonly used pharmaceutical
      formulation for iron supplementation, there are few studies comparing different
      iron salts in infants. OBJECTIVE: This is a study of retrospective data
      comparison of two groups of preterm infants receiving erythropoietin to evaluate
      the efficacy of iron bisglycinate chelate to iron sulfate. SUBJECTS AND METHODS:
      Three-hundred infants of gestational age <=32 weeks were enrolled: 225 were
      supplemented with iron sulfate (3 mg/kg/day) and 75 were supplemented with iron
      bisglycinate chelate (0.75 mg/kg/day). The effect on erythropoiesis was assessed
      with a general linear model that estimates the response variables (values for
      Haemoglobin, Haematocrit, absolute values and percentage Reticulocytes,
      Reticulocyte Haemoglobin content) based on treatment, time, birth weight, and
      gestational age. RESULTS: Supplementation with iron bisglycinate chelate at a
      dose of 0.75 mg/kg/day demonstrated an efficacy comparable to iron sulfate at a
      dose of 3 mg/kg/day in both populations of preterm infants. The two cohorts had
      similar erythropoietic response, without significant differences. CONCLUSIONS:
      The higher bioavailability of iron bisglycinate chelate resulted in a lower load
      of elemental iron, a quarter of the dose, and achieved equivalent efficacy
      compared to iron sulfate. Iron bisglycinate chelate may appear to be an
      alternative to iron sulfate in the prevention and treatment of preterm newborn
      anaemia.

PMID- 29366420
TI  - Predictors of Non-Alcoholic Liver Disease in Ethnically Diverse Overweight
      Children and Adolescents.
AB  - OBJECTIVES: To study the relationship between Non-Alcoholic Fatty Liver Disease
      (NAFLD) and sleep, Physical Activity (PA), and screen-time habits/behaviors among
      a multiethnic sample of overweight children/adolescents. METHODS: A retrospective
      medical chart review (6/2013-7/2014) identified 209 patients (7-21 years old) who
      were overweight/obese (BMI > 85th% for age/sex). A follow-up telephone survey was
      completed among 130 of these patients' parents to obtain information on sleep,
      screen-time, PA habits, and socio-demographics. NAFLD was defined as ALT and/or
      AST levels above the age/sexadjusted cutoff value in the absence of medications
      or associated medical conditions. Logistic regression models were fitted to
      identify predictors of NAFLD by adjusting age, sex, heritage, and income.
      RESULTS: Over a third (34%) of the sample (N=130, 55% males, 74% Hispanic) had
      NAFLD. Compared to non-Hispanics, Central American heritage subjects were over
      three times as likely to have NAFLD compared to non-Hispanics (OR=3.90, 95% CI,
      1.23-12.37) after adjusting for socioeconomics and lifestyle habits. Subjects
      with low PA levels were at increased risk for NAFLD (aOR=4.52, 95% CI, 1.21
      16.82) compared to their more active counterparts. Lower income families were
      over twice as likely to have NAFLD as higher income families (OR = 2.57, 0.95
      6.96). CONCLUSIONS: Families residing from a Central American heritage are at
      significant risk for NAFLD versus their ethnic group counterparts. Identifying
      specific groups and risks for pediatric-onset NAFLD can inform and improve
      clinical practice and public health initiatives, especially as patient
      populations become more ethnically diverse across the nation.

PMID- 29366421
TI  - Radial Polydactyly. What's New?
AB  - BACKGROUND: Thumb duplication, also called radial or preaxial polydactyly, is
      classified as an alteration of the radio-ulnar axis in the formation and
      differentiation of the hand plate, according to the Oberg, Manske and Tonkin
      classification. OBJECTIVE: Radial polydactyly is a common upper limb
      malformation. This paper is a comprehensive analysis of radial polydactyly, its
      genetic explanation, classification, surgical techniques, functional results, as
      well as present and future scientific evidence on this congenital pathology.
      CONCLUSIONS: Radial polydactyly occurs most frequently as an isolated defect, but
      it may also occur in association with other abnormalities, or as part of a
      syndrome. The Wassel classification is the universal classification for thumb
      duplication. One of the limitations of it is the misclassification of the
      immature epiphysis. The Wassel classification not only refers to the pathoanatomy
      of the polydactyly but also guides the selection of various surgical techniques.
      Three well-defined surgical objectives should be ensured: thumb alignment,
      stability, and an acceptable final esthetic appearance. Tada score is a validated
      functional scale that takes into account the most common and limiting
      complications, namely clinodactyly and instability. Based on some recent strong
      research evidence, the JSSH assessment system provides the most reliable outcome
      of scores. More studies are required to provide evidence-based conclusions
      regarding the treatment of radial polydactyly.

PMID- 29366422
TI  - Prevalence of Chronic Diabetic Complications in Newly Diagnosed versus Known Type
      2 Diabetic Subjects in a Sample of Alexandria Population, Egypt.
AB  - BACKGROUND: In Egypt, data on the prevalence of chronic diabetic complications,
      which are essential for the adjustment of policies and practices related to
      diabetes care, are scarce. Therefore, the aim of this study was to determine the
      frequency of chronic complications of diabetes; namely neuropathy, diabetic
      kidney disease (DKD), retinopathy and peripheral arterial disease (PAD) in newly
      diagnosed versus known type 2 diabetic patients. SUBJECTS & METHODS: This is a
      cross-sectional study that is based on a previous household survey conducted on a
      representative sample of the population of Alexandria, Egypt. This study included
      506 consecutive subjects with type 2 diabetes; 323 patients with previously known
      T2DM and 183 patients with newly diagnosed T2DM (discovered during the survey).
      For each participant, a focused history was taken. Comprehensive clinical
      examination was done including fundus examination, foot examination and
      assessment of ankle brachial index. Laboratory tests included HbAlc, lipids
      profile, serum creatinine and urinary albumin creatinine ratio (UACR). RESULTS:
      Peripheral neuropathy was detected in 20% of the studied patients; 29.4% of known
      patients and 3.3% of newly diagnosed patients (p<0.001). Diabetic kidney disease
      was detected in 33.2% of the studied patients; 46.1% of known patients and 10.4%
      of newly diagnosed patients (p<0.001). Diabetic retinopathy was detected in 34.6%
      of the studied patients; 48.3% of known patients and 10.4% of newly diagnosed
      patients (p<0.001). Peripheral arterial disease was detected in 32.6% of the
      studied patients; 45.5% of known patients and 9.8% of newly diagnosed patients
      (p<0.001). In patients with known diabetes, the presence of any of the studied
      complications (neuropathy, diabetic kidney disease, retinopathy or PAD) was
      significantly associated with the presence of all other complications (p< 0.001).
      In patients with newly-diagnosed diabetes, the presence of diabetic kidney
      disease was significantly associated with the presence of retinopathy (p<0.001),
      with no significant association with PAD (p=0.357). CONCLUSION: The present study
      confirms that a considerable proportion of people with T2DM have microvascular
      complications and/or PAD at the time of, and possibly years before diagnosis.
      Having shown that, it is strongly recommended to apply appropriate screening
      strategies for subjects with diabetes at the time of diagnosis. Finally, these
      results should be considered as a call for action for the health care planners
      and providers in our region to plan for early screening for diabetes and its
      complications to reduce the disease burden in our community.

PMID- 29366423
TI  - Therapeutic Approach to Patients with Heart Failure with Reduced Ejection
      Fraction and End-stage Renal Disease.
AB  - BACKGROUND: Several risk factors including Ischemic heart disease, uncontrolled
      hypertension, high output Heart Failure (HF) from shunting through vascular
      hemodialysis access, and anemia, contribute to development of HF in patients with
      End-Stage Renal Disease (ESRD). Guidelinedirected medical and device therapy for
      Heart Failure with Reduced Ejection Fraction (HFrEF) has not been extensively
      studied and may have limited safety and efficacy in patients with ESRD. RESULTS:
      Maintenance of interdialytic and intradialytic euvolemia is a key component of HF
      management in these patients but often difficult to achieve. Beta-blockers,
      especially carvedilol which is poorly dialyzed is associated with cardiovascular
      benefit in this population. Despite paucity of data, Angiotensin-converting
      Enzyme Inhibitors (ACEI) or Angiotensin II Receptor Blockers (ARBs) when
      appropriately adjusted by dose and with close monitoring of serum potassium can
      also be administered to these patients who tolerate beta-blockers.
      Mineralocorticoid receptors in patients with HFrEF and ESRD have been shown to
      reduce mortality in a large randomized controlled trial without any significantly
      increased risk of hyperkalemia. Implantable Cardiac-defibrillators (ICDs) should
      be considered for primary prevention of sudden cardiac death in patients with
      HFrEF and ESRD who meet the implant indications. Furthermore in anemic iron
      deficient patients, intravenous iron infusion may improve functional status.
      Finally, mechanical circulatory support with leftventricular assist devices may
      be related to increased mortality risk and the presence of ESRD poses a relative
      contraindication to further evaluation of these devices.

PMID- 29366424
TI  - It's Time to Talk: Challenges in Providing Integrated Palliative Care in Advanced
      Congestive Heart Failure. A Narrative Review.
AB  - BACKGROUND: Congestive heart failure is an increasingly prevalent terminal
      illness in a globally aging population. Prognosis for this disease remains poor
      despite optimal therapy. Evidence suggests that a palliative care approach may be
      beneficial - and is currently recommended - in advanced congestive heart failure
      but these services remain underutilized. OBJECTIVES: To identify the main
      challenges to the access and delivery of palliative care in patients with
      advanced congestive heart failure, and to summarize recommendations for clinical
      practice based on the available literature. METHODS: MEDLINE and EMBASE were
      searched for articles published from 1995-2017 pertaining to end of life care in
      individuals suffering from CHF. Only four randomized controlled trials were
      found. RESULTS: We identified ten key challenges to access and delivery of
      palliative care services in this patient population: (1) Prognostic uncertainty,
      (2) Provider education/training, (3) Ambiguity surrounding coordination of care,
      (4) Timing of palliative care referral, (5) Inadequate community supports, (6)
      Difficulty communicating uncertainty, (7) Fear of taking away hope, (8)
      Insufficient advance care planning, (9) Inadequate understanding of illness, and
      (10) Discrepant patient/family care goals. Provider and patient education, early
      discussion about prognosis, and a multidisciplinary team-based approach are
      recommended as we move towards a model where symptom palliation exists
      concurrently with active disease-modifying therapies. CONCLUSION: Despite
      evidence that palliative care may improve symptom control and quality of life in
      patients with advanced congestive heart failure, a multitude of current
      challenges hinder access to these services. Education, early discussion of
      prognosis and advance care planning, and multidisciplinary team-based care may be
      a helpful initial approach as further targeted work addresses these challenges.

PMID- 29366425
TI  - Hypertriglyceridemia - Common Causes, Prevention and Treatment Strategies.
AB  - BACKGROUND: Prevention and treatment of dyslipidemias represent the key issues of
      Cardiovascular Disease (CVD) prophylaxis. Consequently, the effective management
      of different types of lipid disorders, including hypertriglyceridemia, should be
      a priority for the healthcare practitioners (e.g.: cardiology and endocrinology
      specialists, primary care physicians, dietitians, and pharmacists), who provide
      medical care, as well as for the patients, who receive this care, and need to be
      directly engaged in it, in order to improve their outcomes. The aim of this
      review is to facilitate the translation of current trends in hypertriglyceridemia
      management into a daily practice. The article focuses on the common causes and
      consequences of hypertriglyceridemia, and discusses diagnostic evaluation and
      therapeutic options for patients with high Triglyceride (TG) levels and CVD risk.
      CONCLUSION: This review presents the main practice-related strategies, based on
      the current guidelines for the management of dyslipidemias and CVD risk,
      according to the European Society of Cardiology (ESC), the European
      Atherosclerosis Society (EAS), and the American College of Cardiology
      (ACC)/American Heart Association (AHA), including both non-pharmacological, and
      pharmacological approaches. It also addresses the beneficial impact of
      pharmaceutical Care (PC) interventions on clinical outcomes of patients with
      lipid disorders and CVD risk (in light of Randomized Controlled Trials (RCT)
      data), and underlines the importance of close cooperation between physicians and
      pharmacists, who manage such patients.

PMID- 29366426
TI  - ICE Regimen for Relapsed/Refractory Bone and Soft Tissue Sarcomas in Children.
AB  - BACKGROUND: The outcome of bone and soft tissue sarcomas (BST) after relapse has
      very poor prognosis with survival rates less than 39%. Unfortunately there are
      not many treatment options, but promising responses have been reported with
      ifosfamide, etoposide and carboplatin (ICE). OBJECTIVE: Therefore, we planned a
      study for children with recurrent/refractory BST treated with ICE regimen to
      evaluate their demographic features, responses to treatment and outcome. METHOD:
      Patients with primary diagnosis of BST and treated with ICE regimen at the time
      of first or subsequent relapse, progression or unresponsive disease were selected
      for study. The files were retrospectively evaluated. RESULTS: Thirty of sixty-six
      patients had metastatic disease at relapse. Patients received median 5 cycles of
      ICE and were followed-up median 16.3 months. Overall survival rates were 83% and
      62% at 1st and 2nd year. The ORR to the regimen was 43%. Survival rates were
      significantly higher in good responders (3-year EFS and OS rates: 50% vs. 8% and
      78% vs. 14%; p<0.0001 and p<0.0001). Survival rates for non-metastatic disease
      were 42% and 75% for EFS and OS and higher than patients with metastases at
      relapse (p<0.001 and p<0.0001). EFS and OS rates of patients with
      rhabdomyosarcoma were 42% and 69%. No grade 3 or 4 renal toxicity was documented.
      CONCLUSION: ICE combination improves the outcome of relapsed or refractory
      sarcomas and it might serve as second line treatment. Patients with no metastases
      at relapse would benefit more than others with metastatic disease.

PMID- 29366427
TI  - Synthesis of Novel Thieno[2,3-d]pyrimidine Derivatives and Evaluation of Their
      Cytotoxicity and EGFR Inhibitory Activity.
AB  - BACKGROUND: 4-Substitutedaminoquinazoline scaffolds were reported to possess
      potent cytotoxic and EGFR inhibitory activity such as gefitinib (Iressa),
      erlotinib (Tarceva) and tandutinib. OBJECTIVE: Synthesis of novel 4
      substitutedaminothieno[2,3-d]pyrimidine derivatives as bioisosters of 4
      substitutedaminoquinazoline derivatives with potential cytotoxic and EGFR
      inhibitory activity. METHODS: Novel 4-substitutedaminothieno[2,3-d]pyrimidine
      derivatives 4a-i and 5a-c were synthesized via reacting corresponding 4
      chlorothieno[2,3-d]pyrimidine derivatives 3a-c with N-methylpiperazine,
      morpholine, N-phenylpiperazine or 1,3-propanediamine. Six compounds (2a, 4d, 4e,
      5a-c) were selected by the National Cancer Institute (USA) for evaluating their
      cytotoxic activity using 60 different human tumor cell lines using a single dose
      (10-5 Molar). The rest of the synthesized compounds (2b, 2c, 3a-c, 4a-c and 4f-i)
      were subjected to screening against T47D breast cancer cell line using a single
      dose (10-5 Molar) at Pharmacology lab., Cancer biology lab., Egyptian National
      Institute. Moreover, compounds 2a and 4b-e were subjected to further evaluation
      by IC50 determination. Finally, the inhibition of epidermal growth factor
      receptor (EGFR) was then investigated for the most active compounds 2a and 4d.
      RESULTS: Compounds 2a and 4b-e showed significant cytotoxic activity. Compound 2a
      was more potent than doxorubicin against lung cancer cell line A549 with IC50 =
      13.40 MUM and comparable activity against MCF7. Compound 4d exhibited more potent
      activity than Doxorubicin against prostate PC3 (IC50 = 14.13 uM) while showed
      comparable activity against MCF7 and T47D. CONCLUSION: 4
      Substitutedaminothieno[2,3-d]pyrimidine is a promising backbone for the design
      and synthesis of potent cytotoxic leads.

PMID- 29366428
TI  - HPLC analysis of phenolic acids, antioxidant activity and in vitro effectiveness
      of green and roasted Caffea arabica bean extracts: a comparative study.
AB  - Coffee is a popular drink; it is one of the most commercialized food products and
      a rich source of biologically active compounds that are important for human
      health. This study aimed to prove the anticancer activity of green coffee (GC)
      and roasted coffee (RC) bean aqueous extracts (Coffea arabica) on breast cancer
      adenocarcinoma cell line (MCF-7) and the safety of both extracts on normal human
      peripheral blood lymphocytes culture (HPBL). Total phenolic content for GC and RC
      extracts was measured and result of both extracts were (0.308+/-0.016 & 0.233+/
      0.013mg/g) respectively. The phenolic acids were screened by HPLC at the
      wavelength of 254& 278 and 300 nm and 5-caffeoylquinic acids (Chlorogenic acid),
      the predominant form of phenolic acids, was identified in GC and RC samples.
      Ferric reducing antioxidant power (FRAP) as well as the free radical scavenging
      activity (DPPH) proved the antioxidant properties of both extracts. The DPPH IC50
      mean values of GC and RC extracts were (2.4+/-0.08, 2.3+/-0.16 MUg/ml)
      respectively. Cytotoxicity of both extracts on MCF-7 cells were evaluated by
      neutral red uptake assay which showed the IC50 mean values (377+/-5.7,500+/-8.1
      MUg/ml) for GC and RC extracts respectively. The safety of both extracts (0, 125,
      250, 500 MUg/ml) on HPBL was evaluated in vitro using trypan blue exclusion
      method and DNA single strand breaks (alkaline comet assay). Result revealed non
      significant cytotoxic difference (P<0.001) between cultures especially at lower
      doses of GC and RC extracts except the highest dose of BC and GC extract which
      showed slightly significant damage (P<0.001). In conclusion, this study proved
      that GC and RC aqueous extracts were found to be selectively cytotoxic in vitro
      to cancerous cells (MCF-7 cell line) causing cell death with no cytotoxicity on
      normal human lymphocytes especially at lower doses.

PMID- 29366429
TI  - New insights on Ethambutol targets in Mycobacterium tuberculosis.
AB  - BACKGROUND: In recent years, very few effective drugs against Mycobacterium
      tuberculosis (M. tb) have emerged which motivates the research with drugs already
      used in the treatment of tuberculosis. EMB is a bacteriostatic drug that affects
      cell wall integrity, but the effects of this drug on bacilli are not fully
      exploited. OBJECTIVE: Based on the need to better investigate the complex
      mechanism of action of EMB, our study presented the proteome profile of M. tb
      after different times of EMB exposure, aiming to comprehend the dynamics of
      bacilli response to its effects. METHOD: M. tb was exposed to subinhibitory
      concentration of EMB for 24 h and 48 h. The proteins were identified by MALDI-
      TOF/TOF. RESULTS: The main protein changes occurred in metabolic proteins as
      dihydrolipoyl dehydrogenase [LpdC] (Rv0462), glutamine synthetase1 [GlnA1]
      (Rv2220), electron transfer flavoprotein subunit beta [ETF-beta] (Rv3029c) and
      adenosylhomocysteinase [SahH] (Rv3248c). CONCLUSION: Considering the functions of
      these proteins our results support that the intermediary metabolism and
      respiration were affected by EMB and this disturbance provided proteins that
      could be explored as additional targets for this drug.

PMID- 29366430
TI  - Distribution and Characterization of the Vitis vinifera L. subsp sylvestris in
      Southern Tuscany.
AB  - BACKGROUND: The Eurasian grapevine is the most widespread fruit crop in the
      world. Numerous studies have focused on clarifying the events of domestication
      and the geographical areas in which they occurred. OBJECTIVES: In order to add
      upon information on the process of grapevine domestication, the distribution and
      genetic diversity of a small, wild population localized in Poggio Ghiaccio Forte,
      an archaeological site in Maremma (Southern Tuscany), were assessed. In a
      preliminary survey the wild forms of Vitis vinifera L. were identified based on
      morphological traits. METHOD: Fourty-two accessions of Vitis vinifera ssp.
      sylvestris were collected near the Albegna river and its secondary conduits. As a
      control, four non-vinifera grapevines (Vitis berlandieri, Vitis riparia Fabre,
      rupestris Constantia, rupestris H. Goethe) and ten varieties of Vitis vinifera
      ssp. sativa characterizing the Tuscan grapevine germplasm (Sangiovese,
      Ciliegiolo, Aleatico, Ansonica, Canaiolo Nero, Trebbiano Toscano, Barsaglina,
      Malvasia Lunga, Moscato Bianco, Abrusco) were added to the wild population. All
      fifty-six vines were treated as one population and tested by 10 SSR-based
      genotyping. RESULTS: According to SSR analysis, the wild population seems to be
      characterized by a systematic reduction of observed compared to expected
      heterozygosity due to the tendency of inbreeding and genetic trait fixation.
      There are a lot of registered patents about different applications involving
      Vitis vinifera mostly relating to disease resistance, grapevine fitness and novel
      combinations of antioxidants useful in therapeutic, foodstuff and cosmetic
      fields.

PMID- 29366431
TI  - Prednisolone Effects on Urine Cross-Linked N-Telopeptides of Type I Collagen
      (Ntx) Diurnal Rhythms in Children.
AB  - BACKGROUND: Recently, methods for mimicking endogenous cortisol rhythms hereby
      potentially reducing the risk of systemic adverse effects of exogenous
      corticosteroids have been patented. Methods for sensitive detection of adverse
      effects on bone turnover of various doses, administration routes and regimens of
      exogenous corticosteroids have been patented. Urine cross-linked Ntelopeptides of
      Type I collagen (Ntx) have been established as a sensitive bone resorption marker
      and urine levels of Ntx have been found to exhibit a distinct diurnal rhythm.
      OBJECTIVE: To assess whether the timing of administration of prednisolone affects
      the diurnal rhythm of Ntx in urine. METHODS: Four girls and four boys aged 10.6
      to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV
      were studied in an open randomized 2-periods cross-over trial, with a 1-day run
      in, and two 4-day periods of 5mg prednisolone in the morning and in the evening,
      respectively, separated by a 3-week washout period. At run in and on the last day
      of each treatment period, the first sample of urine was collected from 24.00 to
      08.00h in the morning of the day of investigation. Thereafter, urine was
      collected in 4~hour intervals until 24.00 and in another 08.00h interval from
      24.00 to 08.00h. RESULTS: Compared to run in and morning prednisolone treatment
      urine Ntx levels were suppressed from 24.00 to 8.00h during treatment with
      prednisolone in the evening (P < 0.01 for both comparisons) and no statistically
      significant circadian rhythm was observed. During morning prednisolone treatment
      Ntx trough and peak levels occurred from 16.00 to 20.00 and 24.00 to 08.00h,
      respectively, and the Ntx levels were significantly reduced from 12.00 to 20.00h
      as compared to run in (P < 0.005) and prednisolone treatment in the evening (P <
      0.01). CONCLUSIONS: Depending on the time of administration, prednisolone
      interferes with diurnal rhythms in urine Ntx.

PMID- 29366432
TI  - Manage Your Life Online: A Web-Based Randomized Controlled Trial Evaluating the
      Effectiveness of a Problem-Solving Intervention in a Student Sample.
AB  - BACKGROUND: Evidence for the efficacy of computer-based psychological
      interventions is growing. A number of such interventions have been found to be
      effective, especially for mild to moderate cases. They largely rely on
      psychoeducation and 'homework tasks', and are specific to certain diagnoses (e.g.
      depression). AIMS: This paper presents the results of a web-based randomized
      controlled trial of Manage Your Life Online (MYLO), a program that uses
      artificial intelligence to engage the participant in a conversation across any
      problem topic. METHOD: Healthy volunteers (n = 213) completed a baseline
      questionnaire and were randomized to the MYLO program or to an active control
      condition where they used the program ELIZA, which emulates a Rogerian
      psychotherapist. Participants completed a single session before completing post
      study and 2-week follow-up measures. RESULTS: Analyses were per protocol with
      intent to follow-up. Both programs were associated with improvements in problem
      distress, anxiety and depression post-intervention, and again 2 weeks later, but
      MYLO was not found to be more effective than ELIZA. MYLO was rated as
      significantly more helpful than ELIZA, but there was no main effect of
      intervention on problem resolution. CONCLUSIONS: Findings are consistent with
      those of a previous smaller, laboratory-based trial and provide support for the
      acceptability and effectiveness of MYLO delivered over the internet for a non
      clinical sample. The lack of a no-treatment control condition means that the
      effect of spontaneous recovery cannot be ruled out.

PMID- 29366433
TI  - Evaluating the Effectiveness of a Dialectical Behaviour Therapy (DBT) Informed
      Programme in a Community Perinatal Team.
AB  - BACKGROUND: Adapted DBT programmes have been well documented but little has been
      published on such programmes in the perinatal period. AIM: To assess the
      effectiveness of a stand-alone DBT skills group for perinatal women with emotion
      dysregulation. METHOD: A stand-alone DBT-informed skills training group was
      offered to 21 women with emotional dysregulation under the care of a perinatal
      community mental health team; 14 completed the programme. Staff received support
      via a consultation group. Modules included mindfulness, emotional regulation,
      distress tolerance and interpersonal effectiveness adapted to the specific
      demands of parenting infants. Outcome measures were collected at three time
      points: assessment, start of the group and at the end. RESULTS: Statistical
      analysis showed significant reduction in CORE scores over the intervention period
      (t (13) = 5.32, p < .001; Cohen's d = 0.83), with similar effects on the Mental
      Health Confidence Scale (t (13) = -8.03, p < .001, Cohen's d = 0.83) and Living
      with Emotions Scale (t (13) = -9.42, p < .001, Cohen's d = 0.93). There were no
      significant changes on these three measures from assessment to start of the
      group. CONCLUSIONS: In this uncontrolled study, the intervention period was
      associated with reduced distress, increased confidence and ability to regulate
      emotion. Recommendations for continuing this model of service delivery are made.
      Further research is needed.

PMID- 29366435
TI  - Anorexia nervosa treatments and Occam's razor.

PMID- 29366434
TI  - Screening for Asymptomatic Clostridium difficile Among Bone Marrow Transplant
      Patients: A Mixed-Methods Study of Intervention Effectiveness and Feasibility.
AB  - OBJECTIVE To identify facilitators and barriers to implementation of a
      Clostridium difficile screening intervention among bone marrow transplant (BMT)
      patients and to evaluate the clinical effectiveness of the intervention on the
      rate of hospital-onset C. difficile infection (HO-CDI). DESIGN Before-and-after
      trial SETTING A 505-bed tertiary-care medical center PARTICIPANTS All 5,357
      patients admitted to the BMT and general medicine wards from January 2014 to
      February 2017 were included in the study. Interview participants included 3
      physicians, 4 nurses, and 4 administrators. INTERVENTION All BMT patients were
      screened within 48 hours of admission. Colonized patients, as defined by a C.
      difficile-positive polymerase chain reaction (PCR) stool result, were placed
      under contact precautions for the duration of their hospital stay. METHODS
      Interview responses were coded according to the Systems Engineering Initiative
      for Patient Safety conceptual framework. We compared pre- and postintervention HO
      CDI rates on BMT and general internal medicine units using time-series analysis.
      RESULTS Stakeholder engagement, at both the person and organizational level,
      facilitates standardization and optimization of intervention protocols. While the
      screening intervention was generally well received, tools and technology were
      sources of concern. The mean incidence of HO-CDI decreased on the BMT service
      postintervention (P<.0001). However, the effect of the change in the trend
      postintervention was not significantly different on BMT compared to the control
      wards (P=.93). CONCLUSIONS We report the first mixed-methods study to evaluate a
      C. difficile screening intervention among the BMT population. The positive nature
      by which the intervention was received by front-line clinical staff, laboratory
      staff, and administrators is promising for future implementation studies. Infect
      Control Hosp Epidemiol 2018;39:177-185.

PMID- 29366436
TI  - Effect of orexin B on CYP17A1 and CYP19A3 expression and oestradiol, oestrone and
      testosterone secretion in the porcine uterus during early pregnancy and the
      oestrous cycle.
AB  - Orexin A (OXA) and B (OXB) are hypothalamic neuropeptides identified as
      regulators of food intake, energy homoeostasis, sleep-wake cycle and arousal.
      They also create an integrative link between energy homoeostasis and
      reproduction. Although their functions in the ovaries and testes have been
      partially explored, to date, less attention has been focused on the role of the
      peptides in the uterus. The aim of this study was to investigate the effect of
      one of orexins - orexin B on oestradiol (E2), oestrone (E1) and testosterone (T)
      secretion by porcine endometrial and myometrial slices as well as the gene
      expression of key steroidogenic enzymes responsible for steroid production
      (CYP17A1, CYP19A3) during the luteal phase of the oestrous cycle (days 10 to 11)
      and early pregnancy (days 10 to 11, 12 to 13, 15 to 16, 27 to 28). Orexin B
      suppressed E2 secretion by endometrial slices on days 10 to 11 and 15 to 16 of
      pregnancy, and days 10 to 11 of the cycle. In the myometrium, OXB inhibited E2
      production on days 10 to 11 of pregnancy, whereas on days 12 to 13 it enhanced
      steroid output. Endometrial E1 release was potentiated by the peptide during all
      studied periods of the cycle and pregnancy, with the exception of days 12 to 13,
      when an inhibitory effect was observed. Myometrial secretion of E1 was increased,
      except on days 27 to 28. Testosterone secretion by endometrial slices was
      increased on days 12 to 13 and 27 to 28 of pregnancy. On days 10 to 11 of the
      cycle, T release was stimulated in response to the lowest and decreased under the
      influence of the highest dose of OXB. In the myometrium, T production was
      inhibited by OXB on days 10 to 11 of pregnancy and during the corresponding
      period of the cycle. On days 27 to 28 of pregnancy, T release was potentiated by
      the lowest dose of OXB. Expression of both genes was modified by OXB depending on
      the period of pregnancy and the type of examined uterine tissues. Our findings
      suggest that OXB, through modulation of uterine steroidogenesis, may have a
      regulatory role in the uterus.

PMID- 29366437
TI  - Rising inequality and the implications for the future of private insurance in
      Canada.
AB  - Income and wealth inequality have risen in Canada since its low point in the
      1980s. Over that same period we have also seen an increase in the amount that
      Canadians spend on privately financed health care, both directly and through
      private health insurance. This paper will explore the relationship between these
      two trends using both comparative data across jurisdictions and household-level
      data within Canada. The starting hypothesis is that the greater the level of
      inequality the more difficult it becomes for publicly provided insurance to
      satisfy the median voter. Thus, we should expect increased pressure to access
      privately financed alternatives as inequality increases. In the light of these
      implications, the paper considers the implications for the future of private
      insurance in Canada.

PMID- 29366438
TI  - Changes in Emotion Processing following Brief Augmented Psychodynamic
      Interpersonal Therapy for Functional Neurological Symptoms.
AB  - BACKGROUND: Functional neurological symptoms (FNS) are considered non-volitional
      and often very disabling, but are not explainable by neurological disease or
      structural abnormalities. Brief Augmented Psychodynamic Interpersonal Therapy
      (BAPIT) was adapted to treat the putative emotion processing deficits thought to
      be central to FNS aetiology and maintenance. BAPIT for FNS has previously been
      shown to improve levels of distress and functioning, but it is unknown whether
      improvements on such measures correlate with changes in emotion processing -
      which this treatment focuses on. AIM: To determine (a) whether the recently
      developed Emotional Processing Scale-25 can be used to demonstrate BAPIT
      associated changes in patients with FNS, and (b) whether changes in the EPS-25
      are associated with changes in previously validated outcome measures. METHOD: 44
      patients with FNS completed questionnaires including the EPS-25 and measures of
      clinical symptomology (health-related quality of life (SF-36), somatic symptoms
      (PHQ-15), psychological distress (CORE-10) and illness understanding (BIPQ)) pre-
      and post-therapy. RESULTS: At group level, emotion processing improved following
      therapy (p = .049). Some measures of clinical symptomology also improved, namely
      health-related quality of life (p = .02) and illness understanding (p = .01).
      Improvements in the EPS-25 correlated with improvements in mental health-related
      quality of life and psychological distress. CONCLUSIONS: Emotion processing and
      some measures of clinical symptomology improved in patients with FNS following
      BAPIT. The EPS-25 demonstrated changes that correlated with previously validated
      outcome measures. The EPS-25 is a suitable measure of psychotherapy-associated
      change in the FNS patient population.

PMID- 29366439
TI  - The Barker hypothesis confirmed: association of low birth weight with all-cause
      natural deaths in young adult life in a remote Australian Aboriginal community.
AB  - Barker et al. proposed that low birth weight predisposes to higher death rates in
      adult life. We previously confirmed this fact in a cohort of young adults who
      were born in a remote Australian Aboriginal community between 1956 and 1985. We
      now present data in these same people with four more years of follow-up and a
      greater number of deaths. The fates of participants were documented from age 15
      years until death, start of dialysis, or until the end of 2010 and causes of
      death were derived from clinic narratives and dialysis records. Rates of natural
      deaths were compared by birth cohorts and birth weight, and hazard ratios were
      calculated using Cox proportional hazards methods, by birth weight and adjusted
      for birth cohort and sex. Over follow-up of 19,661 person-years, 61 people died
      of natural causes between age 15 and the censor date. Low birth weights (<2.5 kg)
      were associated with higher rates of natural death, with HR (95% CI) 1.76 (1.1
      2.9, P=0.03), after adjustment for year of birth and sex. The effect was
      particularly prominent for deaths at <41 years of age, and with deaths from
      respiratory conditions/sepsis and unusual causes. A predisposing effect of low
      birth weight on adult deaths was confirmed. This phenomenon, occurring in the
      context of dramatically improved survivals of lower birth weight infants and
      children since the early 1960s, helps explain the current epidemic of chronic
      disease in Aboriginal people. Birth weights continue to improve, so excess deaths
      from this source should progressively be minimized.

PMID- 29366440
TI  - Supplementary physicians' fees: a sustainable system?
AB  - In Belgium and France, physicians can charge a supplementary fee on top of the
      tariff set by the mandatory basic health insurance scheme. In both countries, the
      supplementary fee system is under pressure because of financial sustainability
      concerns and a lack of added value for the patient. Expenditure on supplementary
      fees is increasing much faster than total health expenditure. So far, measures
      taken to curb this trend have not been successful. For certain categories of
      physicians, supplementary fees represent one-third of total income. For patients,
      however, the added value of supplementary fees is not that clear. Supplementary
      fees can buy comfort and access to physicians who refuse to treat patients who
      are not willing to pay supplementary fees. Perceived quality of care plays an
      important role in patients' willingness to pay supplementary fees. Today, there
      is no evidence that physicians who charge supplementary fees provide better
      quality of care than physicians who do not. However, linking supplementary fees
      to objectively proven quality of care and limiting access to top quality care to
      patients able and willing to pay supplementary fees might not be socially
      acceptable in many countries. Our conclusion is that supplementary physicians'
      fees are not sustainable.

PMID- 29366441
TI  - Oxygen matters: hypoxia as a pathogenic mechanism in rhinosinusitis.
AB  - The airway epithelium is the first place, where a defense mechanism is initiated
      against environmental stimuli. Mucociliary transport (MCT), which is the defense
      mechanism of the airway and the role of airway epithelium as mechanical barriers
      are essential in innate immunity. To maintain normal physiologic function, normal
      oxygenation is critical for the production of energy for optimal cellular
      functions. Several pathologic conditions are associated with a decrease in oxygen
      tension in airway epithelium and chronic sinusitis is one of the airway diseases,
      which is associated with the hypoxic condition, a potent inflammatory stimulant.
      We have observed the overexpression of the hypoxia-inducible factor 1 (HIF-1), an
      essential factor for oxygen homeostasis, in the epithelium of sinus mucosa in
      sinusitis patients. In a series of previous reports, we have found hypoxia
      induced mucus hyperproduction, especially by MUC5AC hyperproduction, disruption
      of epithelial barrier function by the production of VEGF, and down-regulation of
      junctional proteins such as ZO-1 and E-cadherin. Furthermore, hypoxia-induced
      inflammation by HMGB1 translocation into the cytoplasm results in the release of
      IL-8 through a ROS-dependent mechanism in upper airway epithelium. In this mini
      review, we briefly introduce and summarize current progress in the pathogenesis
      of sinusitis related to hypoxia. The investigation of hypoxia-related
      pathophysiology in airway epithelium will suggest new insights on airway
      inflammatory diseases, such as rhinosinusitis for clinical application and drug
      development. [BMB Reports 2018; 51(2): 59-64].

PMID- 29366442
TI  - DNA binding partners of YAP/TAZ.
AB  - Hippo signaling plays critical roles in regulation of tissue homeostasis, organ
      size, and tumorigenesis by inhibiting YES-associated protein (YAP) and PDZ
      binding protein TAZ through MST1/2 and LATS1/2 pathway. It is also engaged in
      cross-talk with various other signaling pathways, including WNT, BMPs, Notch,
      GPCRs, and Hedgehog to further modulate activities of YAP/TAZ. Because YAP and
      TAZ are transcriptional coactivators that lack DNA-binding activity, both
      proteins must interact with DNA-binding transcription factors to regulate target
      gene's expression. To activate target genes involved in cell proliferation, TEAD
      family members are major DNA-binding partners of YAP/TAZ. Accordingly, YAP/TAZ
      were originally classified as oncogenes. However, YAP might also play tumor
      suppressing role. For example, YAP can bind to DNA-binding tumor suppressors
      including RUNXs and p73. Thus, YAP might act either as an oncogene or tumor
      suppressor depending on its binding partners. Here, we summarize roles of YAP
      depending on its DNA-binding partners and discuss context-dependent functions of
      YAP/TAZ. [BMB Reports 2018; 51(3): 126-133].

PMID- 29366443
TI  - Hippo-YAP/TAZ signaling in angiogenesis.
AB  - Angiogenesis is a complex, multistep process involving dynamic changes in
      endothelial cell (EC) shapes and behaviors, especially in specialized cell types
      such as tip cells (with active filopodial extensions), stalk cells (with less
      motility) and phalanx cells (with stable junction connections). The Hippo-Yes
      associated protein (YAP)/ transcription activator with PDZ binding motif (TAZ)
      signaling plays a critical role in development, regeneration and organ size by
      regulating cell-cell contact and actin cytoskeleton dynamics. Recently, with the
      finding that YAP is expressed in the front edge of the developing retinal
      vessels, Hippo-YAP/TAZ signaling has emerged as a new pathway for blood vessel
      development. Intriguingly, the LATS1/2-mediated angiomotin (AMOT) family and
      YAP/TAZ activities contribute to EC shapes and behaviors by spatiotemporally
      modulating actin cytoskeleton dynamics and EC junction stability. Herein, we
      summarize the recent understanding of the role of Hippo-YAP/TAZ signaling in the
      processes of EC sprouting and junction maturation in angiogenesis. [BMB Reports
      2018; 51(3): 157-162].

PMID- 29366444
TI  - Regulation of the Hippo signaling pathway by ubiquitin modification.
AB  - The Hippo signaling pathway plays an essential role in adult tissue homeostasis
      and organ size control. Abnormal regulation of Hippo signaling can be a cause for
      multiple types of human cancers. Since the awareness of the importance of the
      Hippo signaling in a wide range of biological fields has been continually grown,
      it is also understood that a thorough and well-rounded comprehension of the
      precise dynamics could provide fundamental insights for therapeutic applications.
      Several components in the Hippo signaling pathway are known to be targeted for
      proteasomal degradation via ubiquitination by E3 ligases. beta-TrCP is a well
      known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The
      Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH)
      which target LATS1/2 for degradation. Regulation via ubiquitination involves not
      only complex network of E3 ligases but also deubiquitinating enzymes (DUBs),
      which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin
      modifications are also known to play important roles in the regulation of Hippo
      signaling. Although there has been much advanced progress in the investigation of
      ubiquitin modifications acting as regulators of the Hippo signaling pathway,
      research done to date still remains inadequate due to the sheer complexity and
      diversity of the subject. Herein, we review and discuss recent developments that
      implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo
      signaling pathway. [BMB Reports 2018; 51(3): 143-150].

PMID- 29366447
TI  - Nutritional status affects the microRNA profile of the hypothalamus of female
      sheep.
AB  - Recent studies on the seasonal regulation of the oestrous cycle in sheep have
      focussed mainly on the responses to photoperiod. However, the brain systems that
      control reproductive activity also respond to nutritional inputs, although the
      molecular mechanisms involved are not completely understood. One possibility is
      that small, non-coding RNAs, such as micro-RNAs (miRNAs), have significant
      influence. In the present study, the amounts and characteristics of miRNAs in
      hypothalamus from oestrous and anestrous ewes, fed low- or high-nutrient diets,
      were compared using Illumina HiSeq sequencing technology. In total, 398 miRNAs,
      including 261 novel miRNAs, were identified in ewes with an enhanced nutritional
      status (HEN), whereas 384 miRNAs, including 247 novel miRNAs, were identified in
      the ewes with a lesser nutritional status (HAN). There were eight conserved and
      140 novel miRNAs expressed differentially between the two libraries. Based on
      quantitative real-time polymerase chain reaction, six miRNAs were assessed to
      verify the accuracy of the library database. Moreover, the correlation between
      the miRNA target and several upstream and downstream genes in the oestrus-related
      pathways were also verified in hypothalamus nerve cells. According to the
      results, nutritional status plays an important role in oestrous regulation in
      sheep, and the hypothalamic processes and pathways induced by nutritional signals
      (folic acid and tyrosine) are different from those induced by photoperiodic
      regulation of oestrus. We have expanded the repertoire of sheep miRNAs that could
      contribute to the molecular mechanisms that regulate the initiation of oestrous
      cycles in anestrous ewes in response to the influence of nutritional status.

PMID- 29366446
TI  - Estrogen-related receptor gamma is a novel catabolic regulator of osteoarthritis
      pathogenesis.
AB  - Osteoarthritis (OA) is the most common form of arthritis and is a leading cause
      of disability with a large socioeconomic cost. OA is a whole-joint disease
      characterized by cartilage destruction, synovial inflammation, osteophyte
      formation, and subchondral bone sclerosis. To date, however, no effective disease
      modifying therapies for OA have been developed. The estrogen-related receptors
      (ERRs), a family of orphan nuclear receptor transcription factors, are composed
      of ERRalpha, ERRbeta, and ERRgamma, which play diverse biological functions such
      as cellular energy metabolism. However, the role of ERRs in OA pathogenesis has
      not been studied yet. Among the ERR family members, ERRgamma is markedly
      upregulated in human and various models of mouse OA cartilage. Adenovirus
      mediated overexpression of ERRgamma in the mouse knee joint tissue caused OA
      pathogenesis. Additionally, cartilage-specific ERRgamma transgenic (Tg) mice
      exhibited enhanced experimental OA. Consistently, ERRgamma in articular
      chondrocytes directly caused expression of matrix metalloproteinase (MMP) 3 and
      MMP13, which play a crucial role in cartilage destruction. In contrast, genetic
      ablation of Esrrg or shRNA-mediated Esrrg silencing in the joint tissues
      abrogated experimental OA in mice. These results collectively indicated that
      ERRgamma is a novel catabolic regulator of OA pathogenesis and can be used as a
      therapeutic target for OA. [BMB Reports 2018; 51(4): 165-166].

PMID- 29366445
TI  - Clinical implications of the Hippo-YAP pathway in multiple cancer contexts.
AB  - The Hippo pathway plays prominent and widespread roles in various forms of human
      carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream
      effector of the Hippo pathway, can lead to excessive cell proliferation and the
      inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP
      is strongly elevated in multiple types of human malignancies such as breast,
      lung, small intestine, colon, and liver cancers. Recent work indicates that,
      surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are
      virtually absent in human cancer, rendering this signaling an unlikely candidate
      to explain the vigorous activation of the YAP in most, if not all human tumors
      and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and
      Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy. The analysis
      of YAP expressions can facilitate the identification of patients who respond
      better to an anti-cancer drug treatment comprising RAF-, MEK-, and EGFR-targeted
      inhibitors. The prominence of YAP for those aspects of cancer biology denotes
      that these factors are ideal targets for the development of anti-cancer
      medications. Therefore, our report strongly indicates that the YAP is of
      potential prognostic utility and druggability in various human cancers. [BMB
      Reports 2018; 51(3): 119-125].

PMID- 29366449
TI  - Multiple Chronic Gouty Tophi.

PMID- 29366448
TI  - Nonsuicidal Self-Injury in Adolescents.
AB  - BACKGROUND: 25-35% of adolescents in random samples drawn from German schools
      have been found to have manifested at least one episode of nonsuicidal self
      injury (NSSI). The prevalence in samples from child and adolescent psychiatric
      clinics is approximately 50%. NSSI can arise as a symptom in the setting of
      various types of mental illness. METHODS: This review is based on a selective
      literature search carried out in the PubMed, PsycINFO, and Cochrane Library
      databases, with special consideration of regional study samples. RESULTS: NSSI is
      usually resorted to as a dysfunctional coping strategy for emotional regulation.
      The main risk factors for NSSI include bullying, accompanying mental illnesses,
      and a history of abuse and neglect in childhood. Neurobiological studies have
      shown abnormal stress processing in persons with NSSI and an elevated pain
      threshold in persons with repetitive NSSI. Psychotherapeutic interventions of
      various kinds lessen the frequency of NSSI; to date, no particular type of
      psychotherapy has been found to be clearly superior to the others. Randomized
      controlled trials have revealed small to moderate effects from dialectic
      behavioral therapy and mentalization-based therapy in adolescent patients. No
      psychoactive drug has yet been found to possess specific efficacy against NSSI in
      adolescents. CONCLUSION: The first ever German-language clinical guidelines for
      the treatment of NSSI have now been issued. Psychotherapy is the treatment of
      first choice. More research is needed so that subgroups with different disease
      courses can be more clearly defined.

PMID- 29366450
TI  - The Treatment of Incisional Hernia.
AB  - BACKGROUND: A meta-analysis of studies from multiple countries has shown that the
      incidence of incisional hernia varies from 4% to 10% depending on the type of
      operation. No epidemiological surveys have been conducted so far. The worst
      possible complication of an incisional hernia if it is not treated surgically is
      incarceration. In this article, we present the main surgical methods of treating
      this condition. We also evaluate the available randomized and controlled trials
      (RCTs) in which open and laparoscopic techniques were compared and analyze the
      patients' quality of life. METHODS: We selectively searched PubMed for relevant
      literature using the search terms "incisional hernia" and "randomized controlled
      trial." 9 RCTs were included in the analysis. The endpoints of the meta-analysis
      were the number of reoperations, complications, and recurrences. The observed
      events were studied statistically by correlation of two unpaired groups with a
      fixed-effects model and with a random-effects model. We analyzed the quality of
      life in our. RESULTS: Open surgery and laparoscopic surgery for the repair of
      incisional hernias have similar rates of reoperation (odds ratio [OR] 0.419
      favoring laparoscopy, 95% confidence interval [0.159; 1.100]; p = 0.077). The
      rates of surgical complications are also similar (OR 0.706; 95% CI [0.278;
      1.783]; p = 0.461), although the data are highly heterogeneous, and the
      recurrence rates are comparable as well (OR 1.301; 95% CI [0,761; 2,225]; p =
      0.336). In our own patient cohort in Wurzburg, the quality of life was better in
      multiple categories one year after surgery. CONCLUSION: The operative treatment
      of incisional hernia markedly improves patients' quality of life. The currently
      available evidence regarding the complication rates of open and laparoscopic
      surgical repair is highly heterogeneous, and further RCTs on this subject would
      therefore be desirable. Moreover, new study models are needed so that well
      founded individualized treatment algorithms can be developed.

PMID- 29366451
TI  - Failure to Consider Everyday Pediatric Practice.

PMID- 29366452
TI  - The Cause is Cesarean Section.

PMID- 29366453
TI  - Osteopathy as an Aid to Treatment.

PMID- 29366454
TI  - Caused by Spinal Block.

PMID- 29366455
TI  - In Reply.

PMID- 29366456
TI  - Secondary Syphilis Without Any History of Primary Infection.

PMID- 29366457
TI  - Diffuse Myocardial Interstitial Fibrosis and Dysfunction in Early Chronic Kidney
      Disease.
AB  - Patients with chronic kidney disease (CKD) have a disproportionately high risk of
      cardiovascular (CV) morbidity and mortality from the very early stages of CKD.
      This excess risk is believed to be the result of myocardial disease commonly
      termed uremic cardiomyopathy (UC). It has been suggested that interstitial
      myocardial fibrosis progresses with advancing kidney disease and may be the key
      mediator of UC. This longitudinal study reports data on the myocardial structure
      and function of 30 patients with CKD with no known cardiovascular disease and
      healthy controls. All patients underwent cardiac magnetic resonance imaging
      including T1 mapping and late gadolinium enhancement (if estimated glomerular
      filtration rate > 30 ml/min/1.73 m2). Over a mean follow-up period of 2.7 +/- 0.8
      years, there was no change in left ventricular mass, volumes, ejection fraction,
      native myocardial T1 times, or extracellular volume with CKD or in healthy
      controls. Global longitudinal strain (20.6 +/- 2.9 s-1 vs 19.8 +/- 2.9 s-1, p =
      0.03) and mitral annular planar systolic excursion (13 +/- 2 mm vs 12 +/- 2 mm, p
      = 0.009) decreased in CKD but were clinically insignificant. Midwall late
      gadolinium enhancement was present in 4 patients at baseline and was unchanged at
      follow-up. Renal function was stable in this cohort over follow-up (change in
      estimated glomerular filtration rate was -3 ml/min/1.73 m2) with no adverse
      clinical CV events. In conclusion, this study demonstrates that in a cohort of
      patients with stable CKD, left ventricular mass, native T1 times, and
      extracellular volume do not increase over a period of 2.7 years.

PMID- 29366458
TI  - An end to linings under posterior composites?
AB  - BACKGROUND AND OVERVIEW: There is an uncertainty among dentists as to whether to
      place a lining under a direct posterior composite restoration and, if so, what
      material or combination of materials to use. In this article, the authors
      consider the evidence for the placement of a lining under posterior composites of
      different depths, including indications and contraindications for different
      lining materials. CONCLUSIONS: The available evidence does not support the use of
      linings under direct, bonded posterior composites, unless being placed in deep
      cavities for therapeutic reasons. PRACTICAL IMPLICATIONS: The best available
      evidence indicates that dentists can place posterior composites without linings,
      except for therapeutic purposes, with no adverse effect on postoperative
      complications, with possible improvements in performance in clinical service, and
      with efficiency savings in chairside time.

PMID- 29366459
TI  - International Symposium on Salmonella and salmonellosis.

PMID- 29366460
TI  - Sewage sludge amendment and inoculation with plant-parasitic nematodes do not
      facilitate the internalization of Salmonella Typhimurium LT2 in lettuce plants.
AB  - Contamination of fruits and vegetables with Salmonella is a serious threat to
      human health. In order to prevent possible contaminations of fresh produce it is
      necessary to identify the contributing ecological factors. In this study we
      investigated whether the addition of sewage sludge or the presence of plant
      parasitic nematodes foster the internalization of Salmonella enterica serovar
      Typhimurium LT2 into lettuce plants, posing a potential threat for human health.
      Greenhouse experiments were conducted to investigate whether the amendment of
      sewage sludge to soil or the presence of plant-parasitic nematodes Meloidogyne
      hapla or Pratylenchus crenatus promote the internalization of S. Typhimurium LT2
      from soil into the edible part of lettuce plants. Unexpectedly, numbers of
      cultivable S. Typhimurium LT2 decreased faster in soil with sewage sludge than in
      control soil but not in root samples. Denaturing gradient gel electrophoresis
      analysis revealed shifts of the soil bacterial communities in response to sewage
      sludge amendment and time. Infection and proliferation of nematodes inside plant
      roots were observed but did not influence the number of cultivable S. Typhimurium
      LT2 in the root samples or in soil. S. Typhimurium LT2 was not detected in the
      leaf samples 21 and 49 days after inoculation. The results indicate that addition
      of sewage sludge, M. hapla or P. crenatus to soil inoculated with S. Typhimurium
      LT2 did not result in an improved survival in soil or internalization of lettuce
      plants.

PMID- 29366461
TI  - Quantification of hygiene indicators and Salmonella in the tonsils, oral cavity
      and rectal content samples of pigs during slaughter.
AB  - The tonsils, oral cavity and faeces of 94 pigs at slaughter were sampled to
      assess the numbers of total aerobic bacteria, Enterobacteriaceae and Escherichia
      coli in the rectal content, tonsils and oral cavity of pigs at time of
      evisceration. Moreover, the prevalence, numbers and types of Salmonella spp. were
      determined. Mean numbers of Enterobacteriaceae in tonsils and the oral cavity
      differed between slaughterhouses. The proportion of Enterobacteriaceae relative
      to total aerobic bacteria differed between the different tissues, though large
      variations were observed between animals. Salmonella spp. were mostly detected in
      oral cavity swabs (n = 51, 54%), of which six samples were contaminated in
      numbers over 2.0 log CFU/100 cm2. Salmonella spp. were also recovered from 17
      tonsillar tissue samples (18%) and 12 tonsillar swabs (13%). Out of the 29 rectal
      content samples from which Salmonella was recovered (31%), most were lowly
      contaminated, in the range between -1 and 0 log CFU/g. The predominant serotypes
      were S. Typhimurium and its monophasic variant, which were recovered from 33 and
      13 pigs, respectively. In most cases, the same serotypes and MLVA profiles were
      found in pigs slaughtered during the same day, thus suggesting a common source of
      contamination.

PMID- 29366462
TI  - Observations on the introduction and dissemination of Salmonella in three
      previously low prevalence status pig farms in the United Kingdom.
AB  - In the United Kingdom a serological Salmonella surveillance scheme was run in
      pigs up to 2012. Farms that maintained a low seroprevalence (<10%) were
      recognised as "Platinum" pig farms. The aim of this study was to investigate the
      occurrence and distribution of Salmonella in three farms (17P, 18P and 46P) that
      had lost their "Platinum" status. Four visits to each farm were made over a
      period of 15 months. The sampling was carried out by collecting pooled pen floor
      faecal swab and environmental samples. All samples were tested for Salmonella by
      a modification of ISO6579 Annex D, and serovars were determined for all isolates.
      The Salmonella prevalence peaked in the Summer/Autumn months and all farms were
      still positive at the end of the study. The overall sample prevalence was higher
      in farm 17P (46%) and 18P (35%) than 46P (19%). Monophasic S. Typhimurium (mST)
      represented 77.8% of the Salmonella isolates, mainly from farms 17P and 46P. The
      mST isolated at the initial visit may have been introduced via other livestock
      present on farm or introduction into the herd of infected animals. The results of
      this study suggest that incursion of mST was likely to be the main cause of the
      loss of "Platinum" status and confirm that mST can persist in pigs and their
      environment.

PMID- 29366463
TI  - A liquid bead array for the identification and characterization of fljB-positive
      and fljB-negative monophasic variants of Salmonella Typhimurium.
AB  - Salmonella1,4,[5],12:i:- accounts currently for one of the most common serotypes
      observed worldwide. These isolates do not express the FljB flagellin and mostly
      derive from Salmonella Typhimurium. They are therefore termed Salmonella
      Typhimurium monophasic variants (STMV) and are considered of comparable public
      health risk. Since serological identification of the somatic and flagellar
      antigens of STMV is not sufficient to demonstrate relatedness with Salmonella
      Typhimurium, additional assays detecting genetic markers unique to Salmonella
      Typhimurium are required. In addition, identification of the mutations affecting
      expression of the flagellar gene fljB can be useful to support the monophasic
      character observed phenotypically. Finally, genetic subtyping of the various mono
      and biphasic Salmonella Typhimurium clonal groups can facilitate their
      epidemiological follow-up. Here, we present a home-made liquid bead array able to
      fulfill these requirements. This array confirmed the monophasic character of 240
      STMV isolates collected in Belgium during 2014-2015 and identified 10 genetic
      subtypes. Microevolution in and around the fljB locus linked to IS26 insertions
      is probably one of the driven force accounting for STMV population diversity.
      Thanks to its open design, other genetic signatures could later be merged to the
      assay to subtype additional STMV clonal groups and to detect rare mutations.

PMID- 29366464
TI  - The new ISO 6579-1: A real horizontal standard for detection of Salmonella, at
      last!
AB  - Up to 2016, three international standard methods existed for the detection of
      Salmonella spp. in food, animal feed and samples from the primary production
      stage: ISO 6785:2001 for milk and milk products, ISO 6579:2002 for (other) food
      and animal feed and Annex D of ISO 6579:2007 for samples from the primary
      production stage. In 2009, an ISO/CEN working group started with the revision of
      ISO 6579:2002 with two main aims: combining the three aforementioned standards in
      one document and improving the information in ISO 6579:2002. Additionally it was
      decided to split ISO 6579 into three parts, where part 1 describes the detection,
      part 2 the enumeration by mini-MPN (published in 2012) and part 3 the serotyping
      of Salmonella (published in 2014). This paper describes the experiments and
      choices made for improving the part on detection of Salmonella (ISO 6579-1). The
      final voting stage on (draft) ISO 6579-1 was finished by the end of December
      2016, with a positive outcome. Finally, a real horizontal standard became
      available for detection of Salmonella in food, animal feed, environmental samples
      in the area of food production and food handling and in samples from the primary
      production stage in 2017.

PMID- 29366465
TI  - Molecular epidemiology of the endemic multiresistance plasmid pSI54/04 of
      Salmonella Infantis in broiler and human population in Hungary.
AB  - Salmonella Infantis (SI) became endemic in Hungary where the PFGE cluster B,
      characterized by a large multiresistance (MDR) plasmid emerged among broilers
      leading to an increased occurrence in humans. We hypothesized that this plasmid
      (pSI54/04) assisted dissemination of SI. Indeed, Nal-Sul-Tet phenotypes carrying
      pSI54/04 occurred increasingly between 2011 and 2013 among SI isolates from
      broilers and humans. Characterization of pSI54/04 based on genome sequence data
      of the MDR strain SI54/04 indicated a size of ~277 kb and a high sequence
      similarity with the megaplasmid pESI of SI predominant in Israel. Molecular
      characterization of 78 representative broiler and human isolates detected the
      prototype plasmid pSI54/04 and its variants together with novel plasmid
      associations within the emerging cluster B. To test in vitro and in vivo
      pathogenicity of pSI54/04 we produced plasmidic transconjugant of the plasmid
      free pre-emergent strain SI69/94. This parental strain and its transconjugant
      have been tested on chicken embryo fibroblasts (CEFs) and in orally infected day
      old chicks. The uptake of pSI54/04 did not increase the pathogenicity of the
      strain SI69/94 in these systems. Thus, dissemination of SI in poultry could be
      assisted by antimicrobial resistance rather than by virulence modules of the
      endemic plasmid pSI54/04 in Hungary.

PMID- 29366466
TI  - Whole genome sequencing reveals an outbreak of Salmonella Enteritidis associated
      with reptile feeder mice in the United Kingdom, 2012-2015.
AB  - Analysis of whole genome sequencing data uncovered a previously undetected
      outbreak of Salmonella Enteritidis that had been on-going for four years. Cases
      were resident in all countries of the United Kingdom and 40% of the cases were
      aged less than 11 years old. Initial investigations revealed that 30% of cases
      reported exposure to pet snakes. A case-control study was designed to test the
      hypothesis that exposure to reptiles or their feed were risk factors. A robust
      case-definition, based on the single nucleotide polymorphism (SNP) profile,
      increased the power of the analytical study. Following univariable and
      multivariable analysis, exposure to snakes was the only variable independently
      associated with infection (Odds ratio 810 95% CI (85-7715) p < 0.001). Isolates
      of S. Enteritidis belonging to the outbreak profile were recovered from reptile
      feeder mice sampled at the retail and wholesale level. Control measures included
      improved public health messaging at point of sale, press releases and engagement
      with public health and veterinary counterparts across Europe. Mice destined to be
      fed to reptiles are not regarded as pet food and are not routinely tested for
      pathogenic bacteria. Routine microbiological testing to ensure feeder mice are
      free from Salmonella is recommended.

PMID- 29366467
TI  - Epidemiological analysis of Salmonella clusters identified by whole genome
      sequencing, England and Wales 2014.
AB  - The unprecedented level of bacterial strain discrimination provided by whole
      genome sequencing (WGS) presents new challenges with respect to the utility and
      interpretation of the data. Whole genome sequences from 1445 isolates of
      Salmonella belonging to the most commonly identified serotypes in England and
      Wales isolated between April and August 2014 were analysed. Single linkage single
      nucleotide polymorphism thresholds at the 10, 5 and 0 level were explored for
      evidence of epidemiological links between clustered cases. Analysis of the WGS
      data organised 566 of the 1445 isolates into 32 clusters of five or more. A
      statistically significant epidemiological link was identified for 17 clusters.
      The clusters were associated with foreign travel (n = 8), consumption of Chinese
      takeaways (n = 4), chicken eaten at home (n = 2), and one each of the following;
      eating out, contact with another case in the home and contact with reptiles. In
      the same time frame, one cluster was detected using traditional outbreak
      detection methods. WGS can be used for the highly specific and highly sensitive
      detection of biologically related isolates when epidemiological links are
      obscured. Improvements in the collection of detailed, standardised exposure
      information would enhance cluster investigations.

PMID- 29366468
TI  - Evaluation of WGS based approaches for investigating a food-borne outbreak caused
      by Salmonella enterica serovar Derby in Germany.
AB  - In Germany salmonellosis still represents the 2nd most common bacterial foodborne
      disease. The majority of infections are caused by Salmonella (S.) Typhimurium and
      S. Enteritidis followed by a variety of other broad host-range serovars.
      Salmonella Derby is one of the five top-ranked serovars isolated from humans and
      it represents one of the most prevalent serovars in pigs, thus bearing the
      potential risk for transmission to humans upon consumption of pig meat and
      products thereof. From November 2013 to January 2014 S. Derby caused a large
      outbreak that affected 145 primarily elderly people. Epidemiological
      investigations identified raw pork sausage as the probable source of infection,
      which was confirmed by microbiological evidence. During the outbreak isolates
      from patients, food specimen and asymptomatic carriers were investigated by
      conventional typing methods. However, the quantity and quality of available
      microbiological and epidemiological data made this outbreak highly suitable for
      retrospective investigation by Whole Genome Sequencing (WGS) and subsequent
      evaluation of different bioinformatics approaches for cluster definition. Overall
      the WGS-based methods confirmed the results of the conventional typing but were
      of significant higher discriminatory power. That was particularly beneficial for
      strains with incomplete epidemiological data. For our data set both, single
      nucleotide polymorphism (SNP)- and core genome multilocus sequence typing
      (cgMLST)-based methods proved to be appropriate tools for cluster definition.

PMID- 29366469
TI  - Salmonella epidemiology: A whirlwind of change.
AB  - The field of infectious disease epidemiology for Salmonella and other enteric
      pathogens is undergoing some of the most profound changes since the time of
      Kauffman and White. Rapid advances in "big data" technologies such as genomics
      and metagenomics are making it possible to monitor and control salmonellosis in
      new and exciting ways. Epidemiological methods are becoming increasingly robust
      through the routine use of standardized hypothesis-generating questionnaires,
      iterative open-ended interviewing, informational trace-backs and new modeling
      techniques for describing the attribution of disease to food sources. In
      addition, Salmonella epidemiology is facing important challenges and new
      opportunities due to the rapid adoption of culture independent diagnostic test
      panels by clinical laboratories. Where is this unprecedented wave of change
      taking us? This chapter will examine emerging trends in Salmonella epidemiology,
      and take a peek into the not-so-distant future.

PMID- 29366470
TI  - New paradigms for Salmonella source attribution based on microbial subtyping.
AB  - Microbial subtyping is the most common approach for Salmonella source
      attribution. Typically, attributions are computed using frequency-matching models
      like the Dutch and Danish models based on phenotyping data (serotyping, phage
      typing, and antimicrobial resistance profiling). Herewith, we critically review
      three major paradigms facing Salmonella source attribution today: (i) the use of
      genotyping data, particularly Multi-Locus Variable Number of Tandem Repeats
      Analysis (MLVA), which is replacing traditional Salmonella phenotyping beyond
      serotyping; (ii) the integration of case-control data into source attribution to
      improve risk factor identification/characterization; (iii) the investigation of
      non-food sources, as attributions tend to focus on foods of animal origin only.
      Population genetics models or simplified MLVA schemes may provide feasible
      options for source attribution, although there is a strong need to explore novel
      modelling options as we move towards whole-genome sequencing as the standard.
      Classical case-control studies are enhanced by incorporating source attribution
      results, as individuals acquiring salmonellosis from different sources have
      different associated risk factors. Thus, the more such analyses are performed the
      better Salmonella epidemiology will be understood. Reparametrizing current models
      allows for inclusion of sources like reptiles, the study of which improves our
      understanding of Salmonella epidemiology beyond food to tackle the pathogen in a
      more holistic way.

PMID- 29366471
TI  - Theoretical value of pre-trade testing for Salmonella in Swedish cattle herds.
AB  - The Swedish Salmonella control programme includes mandatory action if Salmonella
      is detected in a herd. The aim of this study was to assess the relative value of
      different strategies for pre-movement testing of cattle. Three fictitious herds
      were included: dairy, beef and specialised calf-fattening. The yearly risks of
      introducing Salmonella with and without individual serological or bulk milk
      testing were assessed as well as the effects of sourcing animals from low
      prevalence areas or reducing the number of source herds. The initial risk was
      highest for the calf-fattening herd and lowest for the beef herd. For the beef
      and dairy herds, the yearly risk of Salmonella introduction was reduced by about
      75% with individual testing. Sourcing animals from low-prevalence areas reduced
      the risk by >99%. For the calf-fattening herd, the yearly risk was reduced by
      almost 50% by individual testing or sourcing animals from a maximum of five
      herds. The method was useful for illustrating effects of risk mitigation when
      introducing animals into a herd. Sourcing animals from low-risk areas (or herds)
      is more effective than single testing of individual animals or bulk milk. A
      comprehensive approach to reduce the risk of introducing Salmonella from source
      herds is justified.

PMID- 29366472
TI  - The use of social network analysis to examine the transmission of Salmonella spp.
      within a vertically integrated broiler enterprise.
AB  - To better understand factors influencing infectious agent dispersal within a
      livestock population information is needed on the nature and frequency of
      contacts between farm enterprises. This study uses social network analysis to
      describe the contact network within a vertically integrated broiler poultry
      enterprise to identify the potential horizontal and vertical transmission
      pathways for Salmonella spp. Nodes (farms, sheds, production facilities) were
      identified and the daily movement of commodities (eggs, birds, feed, litter) and
      people between nodes were extracted from routinely kept farm records. Three time
      periods were examined in detail, 1- and 8- and 17-weeks of the production cycle
      and contact networks were described for all movements, and by commodity and
      production type. All nodes were linked by at least one movement during the study
      period but network density was low indicating that all potential pathways between
      nodes did not exist. Salmonella spp. transmission via vertical or horizontal
      pathways can only occur along directed pathways when those pathways are present.
      Only two locations (breeder or feed nodes) were identified where the transmission
      of a single Salmonella spp. clone could theoretically percolate through the
      network to the broiler or processing nodes. Only the feed transmission pathway
      directly connected all parts of the network.

PMID- 29366474
TI  - Bayesian model for tracing Salmonella contamination in the pig feed chain.
AB  - Salmonella infections in pigs are in most cases asymptomatic, posing a risk of
      salmonellosis for pork consumers. Salmonella can transmit to pigs from various
      sources, including contaminated feed. We present an approach for quantifying the
      risk to pigs from contaminations in the feed chain, based on a Bayesian model.
      The model relies on Salmonella surveillance data and other information from
      surveys, reports, registries, statistics, legislation and literature regarding
      feed production and pig farming. Uncertainties were probabilistically quantified
      by synthesizing evidence from the available information over a categorically
      structured flow chain of ingredients mixed for feeds served to pigs. Model based
      probability for infection from feeds together with Salmonella subtyping data,
      were used to estimate the proportion of Salmonella infections in pigs
      attributable to feed. The results can be further used in assessments considering
      the human health risk linked to animal feed via livestock. The presented methods
      can be used to predict the effect of changes in the feed chain, and they are
      generally applicable to other animals and pathogens.

PMID- 29366473
TI  - CRISPR-based assay for the molecular identification of highly prevalent
      Salmonella serotypes.

PMID- 29366475
TI  - Salmonella risk to consumers via pork is related to the Salmonella prevalence in
      pig feed.
AB  - Pigs are an important source of human infections with Salmonella, one of the most
      common causes of sporadic gastrointestinal infections and foodborne outbreaks in
      the European region. Feed has been estimated to be a significant source of
      Salmonella in piggeries in countries of a low Salmonella prevalence. To estimate
      Salmonella risk to consumers via the pork production chain, including feed
      production, a quantitative risk assessment model was constructed. The Salmonella
      prevalence in feeds and in animals was estimated to be generally low in Finland,
      but the relative importance of feed as a source of Salmonella in pigs was
      estimated as potentially high. Discontinuation of the present strict Salmonella
      control could increase the risk of Salmonella in slaughter pigs and consequent
      infections in consumers. The increased use of low risk and controlled feed
      ingredients could result in a consistently lower residual contamination in pigs
      and help the tracing and control of the sources of infections.

PMID- 29366476
TI  - Salmonella Typhimurium metabolism affects virulence in the host - A mini-review.
AB  - Salmonella enterica remains an important food borne pathogen in all regions of
      the world with S. Typhimurium as one of the most frequent serovars causing food
      borne disease. Since the majority of human cases are caused by food of animal
      origin, there has been a high interest in understanding how S. Typhimurium
      interacts with the animal host, mostly focusing on factors that allow it to
      breach host barriers and to manipulate host cells to the benefit of itself. Up to
      recently, such studies have ignored the metabolic factors that allow the bacteria
      to multiply in the host, but this is changing rapidly, and we are now beginning
      to understand that virulence and metabolism in the host are closely linked. The
      current review highlights which metabolic factors that are essential for
      Salmonella Typhimurium growth in the intestine, in cultured epithelial and
      macrophage-like cell lines, at systemic sites during invasive salmonellosis, and
      during long term asymptomatic colonization of the host. It also points to the
      limitations in our current knowledge, most notably that most studies have been
      carried out with few well-characterized laboratory strains, that we do not know
      how much the in vivo metabolism differs between serotypes, and that most results
      are based on challenges in the mouse model of infection. It will be very
      important to realize whether the current understanding of Salmonella metabolism
      in the host is true for all serotypes and all possible hosts.

PMID- 29366477
TI  - NASPAG Position Statement on Surgical Management of DSD.

PMID- 29366478
TI  - Succinate induces hepatic fibrogenesis by promoting activation, proliferation,
      and migration, and inhibiting apoptosis of hepatic stellate cells.
AB  - Liver fibrosis is a progressive pathological process that accompanies wound
      healing; however, therapeutics for reversing hepatic fibrosis are unavailable.
      Activation of hepatic stellate cells (HSCs) play a critical role in liver
      fibrosis. Recent reports showed that succinate and its receptor, G-protein
      coupled receptor 91 (GPR91), act as signaling molecules during the activation of
      HSCs. However, the role of succinate in proliferation, apoptosis, and migration
      of HSCs has not been studied. In this study, we determined whether succinate
      regulates proliferation, apoptosis, and migration of HSCs and induces liver
      fibrosis in a mouse model. Succinate treatment not only induced activation of
      HSCs, but also increased the proliferation and migration of LX-2 HSCs and
      inhibited apoptosis. To investigate whether succinate causes hepatic fibrosis,
      100 mg/kg succinate or control PBS was administered by intraperitoneal injection
      to mice once a day for four weeks. There were significant molecular changes such
      as increased alpha-SMA and collagen type 1 production and increased production of
      inflammatory cytokines such as IL-6 and TNF-alpha, but not TGF-beta, in the
      succinate-treated group compared to the control group. However, no morphological
      changes were observed in Masson's trichrome staining. In conclusion, the present
      study demonstrated that succinate induces activation, proliferation, and
      migration of HSCs and attenuates apoptosis in LX-2 HSCs. Therefore, inhibition of
      succinate accumulation may be an effective method for reversing liver fibrosis by
      controlling HSC survival and growth.

PMID- 29366479
TI  - LncRNA CCND2-AS1 promotes proliferation, migration, and invasion in papillary
      thyroid carcinoma.
AB  - In decades, a lot of long non-coding RNAs (LncRNAs) have been proven to exert
      influences on tumorigenesis in vitro and in vivo. Many lncRNAs have been reported
      as effective therapeutic targets and biomarkers in various cancers. However,
      whether LncRNAs are associated with the progression of PTC remains largely
      unknown. In this study, we measured the expression of CCND2-AS1 in PTC cell lines
      by quantitative real-time polymerase chain reaction (qRT-PCR).We found that CCND2
      AS1 expression was significantly over-expressed in PTC cell lines compared to
      normal thyroid epithelial cells. Gain-and loss-of-function experiments were
      performed to investigate the role of CCND2-AS1 in PTC cells. In vitro
      experiments, we proved that CCND2-AS1 knockdown in TPC1 significantly suppressed
      cell proliferation, migration, and invasion, while CCND2-AS1 overexpression in
      BCPAP had the opposite effects. Meanwhile, we also found that CCND2-AS1 could
      regulate N-cadherin and Vimentin expression, which may influence invasion and
      migration. Our findings indicate that the lncRNA CCND2-AS1 is a gene associated
      with PTC and might become a potential therapeutic target.

PMID- 29366480
TI  - Septin4 as a novel binding partner of PARP1 contributes to oxidative stress
      induced human umbilical vein endothelial cells injure.
AB  - Oxidative stress induced vascular endothelial cell injure is one of the key and
      initial event in the development of atherosclerosis. Septin4, as a member of GTP
      binding protein family, is widely expressed in the eukaryotic cells and
      considered to be an essential component of the cytoskeleton which is involved in
      many important physiological processes. However, whether Septin4 is involved in
      cardiovascular diseases, such as oxidative stress inducted endothelial cell
      injury still unclear. PARP1 as a DNA repair enzyme can be activated by
      identifying DNA damaged fragments, which consumes high levels of energy and leads
      to vascular endothelial cell apoptosis. Here, our results first found that
      Septin4 is involved in oxidative stress induced endothelial cell ROS production
      and apoptosis through knock-down and over-expression Septin4 approaches.
      Furthermore, to explore how Septin4 is involved in oxidative stress induced
      endothelial cells injure, we first identified that Septin4 is a novel PARP1
      interacting protein and the interaction is enhanced under oxidative stress. In
      conclusions, our founding indicates that Septin4 is a novel essential factor
      involved in oxidative stress induced vascular endothelial cell injury by
      interacting with apoptosis-related protein PARP1.

PMID- 29366481
TI  - Discussion of "Risk of major complications following thyroidectomy and
      parathyroidectomy: Utility of the NSQIP surgical risk calculator".

PMID- 29366482
TI  - Breast cancer in women under 50: Most are not high risk.
AB  - BACKGROUND: In 2009, the United States Preventive Services Task Force changed the
      recommended starting age for annual screening mammography from 40 to 50 for non
      "high risk" women. In 2015, the American Cancer Society issued similar
      guidelines, with a starting age of 45. Our hypothesis is that most women
      diagnosed with breast cancer in this age group do not fall into a "high risk"
      category. METHODS: A retrospective review of women less than 50 years of age
      diagnosed with breast cancer in the Legacy Health Care System was performed for
      January 2013 through December 2015. Validated risk assessment models were used to
      quantify risk. High risk was defined as lifetime risk of breast cancer greater
      than 20%. RESULTS: 249 women were identified. Of these, 79 (32%) of women were
      high risk. 170 (68%) did not fall into the high risk category. CONCLUSION: In our
      population, approximately two thirds of women with breast cancer under 50 are non
      "high risk". We argue that women should receive annual mammograms starting at age
      40, because low risk is not protective.

PMID- 29366483
TI  - Self-assessment of team performance using T-NOTECHS in simulated pediatric trauma
      resuscitation is not consistent with expert assessment.
AB  - BACKGROUND: The Trauma NOn-TECHnical Skills (T-NOTECHS) tool has been used to
      assess teamwork in trauma resuscitation, but its reliability and validity for
      self-assessment is unknown. Our purpose was to determine the reliability and
      validity of self-administered T-NOTECHS in pediatric trauma resuscitation.
      METHODS: Simulated in situ resuscitations were evaluated using T-NOTECHS in real
      time by experts and immediately afterwards by team members. Reliability was
      analyzed with linear-weighted kappa and intra-class correlation. T-NOTECHS scores
      were compared between expert (gold-standard) and self-assessment. RESULTS:
      Fifteen simulations were examined. T-NOTECHS scores were similar between self-
      and expert assessment for leadership. Self-assessment scores were higher than
      expert for the other domains and total composite score. Inter-rater reliability
      for total score was similar between the two groups, but differences were observed
      in the domains. CONCLUSIONS: Self-assessment is not interchangeable with expert
      rating when using T-NOTECHS. Future studies need to determine how self-assessment
      can be best utilized. LEVEL OF EVIDENCE: Studies of diagnostic accuracy - Level
      2.

PMID- 29366484
TI  - Discussion of "Protocolized warfarin reversal with 4-factor prothrombin complex
      concentrate versus 3-factor prothrombin complex concentrate with recombinant
      factor VIIa".
AB  - INTRODUCTION: Life-threatening bleeding is the most feared complication of
      warfarin therapy. Rapid anticoagulant reversal via replacement of vitamin K
      dependent clotting factors is essential for hemostasis. METHODS: A retrospective
      cohort study of warfarin-treated patients experiencing a life-threatening bleed
      treated with a warfarin reversal protocol comprised of 4F PCC (post
      implementation group) and those who received the prior reversal protocol of 3F
      PCC and rFVIIa (pre-implementation group) was performed. Demographic and clinical
      information, anticoagulant reversal information, and all adverse events
      attributed to warfarin reversal were recorded. RESULTS: 195 patients were
      included in final analysis; 118 in the pre-implementation group, 77 in the post
      implementation group. While baseline SOFA and GCS scores were similar between
      groups, the pre-implementation group had a longer ICU LOS and higher in-hospital
      mortality (p < .01, .01 respectively). The most common indication for
      anticoagulation reversal was intracranial hemorrhage in both groups. Pre-reversal
      INR was similar between both groups, but post-reversal INR was significantly
      lower in the pre-implementation group, 0.8 versus 1.3 (p < .01). Significantly
      more patients experienced thromboembolic complications (TEC) in the pre
      implementation group than the post-implementation group, 27.9% versus 6.5% of
      patients (p < .01). The leading TEC in both groups was deep venous thrombosis.
      Differences in baseline characteristics (p <= .2) were entered into a Poisson log
      linear regression model for association with TECs. Receipt of rFVIIa was the only
      characteristic significantly associated with TECs. DISCUSSION: A 4F PCC warfarin
      reversal strategy is efficacious at reversing INR while providing significantly
      lower thromboembolic risk as compared to 3F PCC with rVIIa.

PMID- 29366485
TI  - Patient and social characteristics contributing to disparities in outcomes after
      burn injury: application of database research to minority health in the burn
      population.
AB  - BACKGROUND: Although racial disparities have been well described in trauma and
      medical literature, less is known about disparities in the burn population,
      especially the Native American, Hispanic, Black, and Asian minority groups. This
      study seeks to identify at-risk populations for differences in patient and social
      characteristics that may link certain race groups to disparate burn outcomes.
      METHODS: Data was reviewed from the National Burn Repository. Information
      regarding patient demographics, co-morbidities, complications, and clinical
      outcomes was recorded. Student's T-test, ANOVA, and binary logistic regression
      were used to assess relationships between patient factors and outcomes. RESULTS:
      The Native American cohort had higher rates of alcoholism, drug abuse, and
      homelessness compared to all patients. Native Americans also had significantly
      longer hospital lengths of stay, and higher rates of respiratory failure,
      pneumonia, sepsis, and wound complications. The Black population demonstrated the
      highest percentage of injury at home, child abuse, and non-insurance. Mortality
      was highest in the Black population compared to all patients. CONCLUSIONS: These
      findings suggest that outcome disparities exist in burn-injured patients in
      multiple minority groups.

PMID- 29366486
TI  - Effects of radiation and surgery on function and quality of life (QOL) in rectal
      cancer patients.
AB  - Pre-operative radiotherapy (PRT) and total mesorectal excision surgery (TME) for
      rectal cancer yield the lowest risk for local recurrence. However, both
      treatments negatively impact quality of life (QOL). To understand individual
      treatment effects, we ask whether PRT affects function and quality of life before
      TME. Function and QOL were prospectively assessed in 26 patients using EORTC QLQ
      C30/-CR38, and Wexner scale at three time points: before PRT, 6 weeks after PRT
      and before TME, and one year after stoma closure. Wexner score did not change
      post-PRT but did increase post-TME (p < .01). Micturition score did not change
      with PRT or TME (p = .29). Sexual function score improved post-PRT (p = .03) but
      did not change post-TME. Global health status did not change post-treatments (p =
      .45). Future perspective improved post-surgery (p = .04). PRT did not affect
      micturition, bowel function, or QOL. Future perspective improved despite
      increased bowel problems and fecal incontinence. QOL was maintained after
      curative rectal cancer treatments, radiation and TME surgery. This information
      may help patients and physicians better understand effects of PRT and TME
      treatments for rectal cancer.

PMID- 29366487
TI  - Complications and their associations following the surgical repair of pressure
      ulcers.
AB  - BACKGROUND: Despite high expenditure, there is little national data on rates of
      complications following pressure ulcer repair. Complications, mortality and their
      predictors following surgical repair of pressure ulcers were evaluated. METHODS:
      Patients undergoing pressure ulcer repair were identified in the NSQIP database
      from 2005 to 2015. Regression models were used to identify risk factors for
      complications. RESULTS: 1248 cases were identified with a complication rate of
      35.0%. Obesity was associated with increased risk of complications, whereas flap
      closure was associated with fewer complications. Thirty-day mortality was 3.3%.
      Elderly age and diabetes were associated with increased mortality. CONCLUSIONS:
      Elderly age, diabetes and dependency are associated with increased mortality
      following pressure ulcer surgery. Flap repair is associated with decreased
      complications. Pressure ulcer reconstruction requires careful patient selection
      and surgical technique to mitigate risks and mortality.

PMID- 29366488
TI  - Repeatability of Cervical Joint Flexion and Extension Within and Between Days.
AB  - OBJECTIVE: The purpose of this study was to investigate within- and between-day
      repeatability of free and unrestricted healthy cervical flexion and extension
      motion when assessing dynamic cervical spine motion. METHODS: Fluoroscopy videos
      of 2 repeated cervical flexion and 2 repeated extension motions were examined for
      within-day repeatability (20-second interval) for 18 participants (6 females) and
      between-day repeatability (1-week interval) for 15 participants (6 females). The
      dynamic cervical motions were free and unrestricted from neutral to end range.
      The flexion videos and extension videos were evenly divided into 10% epochs of
      the C0-to-C7 range of motion. Within-day and between-day repeatability of joint
      motion angles (all 7 joints and epochs, respectively) was tested in a repeated
      measures analysis of variance. Joint motion angle differences between repetitions
      were calculated for each epoch and joint (7 joints), and these joint motion angle
      differences between within-day and between-day repetitions were tested in mixed
      model analysis of variance. RESULTS: For all joints and epochs, respectively, no
      significant differences were found in joint motion angle between within-day or
      between-day repetitions. There were no significant effects of joint motion angle
      differences between within-day and between-day repetitions. The average within
      day joint motion angle differences across all joints and epochs were 0.00 degrees
      +/- 2.98 degrees  and 0.00 degrees  +/- 3.05 degrees  for flexion and extension,
      respectively. The average between-day joint motion angle differences were 0.02
      degrees  +/- 2.56 degrees  and 0.05 degrees  +/- 2.40 degrees  for flexion and
      extension, respectively. CONCLUSIONS: This is the first study to report the
      within-day and between-day joint motion angle differences of repeated cervical
      flexion and extension. This study supports the idea that cervical joints repeat
      their motion accurately.

PMID- 29366489
TI  - Glucocorticoid-Induced Changes in Rat Skeletal Muscle Biomechanical and
      Viscoelastic Properties: Aspects of Aging.
AB  - OBJECTIVES: The purpose of this study was to estimate the state of tension (tone)
      and the biomechanical and viscoelastic properties of skeletal muscle in aging
      rats during the administration of different doses of dexamethasone and to find
      the relationships among the state of muscle atrophy, muscle strength, and the
      abovementioned muscle properties. METHODS: Muscle state of tension, biomechanical
      (elasticity, dynamic stiffness) and viscoelastic (mechanical stress relaxation
      time, Deborah number) properties (using MyotonPRO, Myoton Ltd, Tallinn, Estonia),
      lean body mass (BM), and hind limb grip strength were measured before and after
      the administration of a 10-day treatment with dexamethasone 100 MUg/100 g BM
      (young and old group) and 50 MUg/100 g BM (old group). RESULTS: Muscle elasticity
      (logarithmic decrement) was lower in old animals (1.86 +/- 0.03) in comparison
      with young adult rats (1.38 +/- 0.04) (P < .01). After the 10-day treatment with
      dexamethasone 100 MUg/100 g BM, young adult rats had 10% lower muscle elasticity
      (P < .01). The same dose of dexamethasone in old rats increased tone (frequency
      of natural oscillation) from 29.13 +/- 0.51 Hz to 38.50 +/- 0.95 Hz (P < .001).
      There were dose-dependent differences in dynamic stiffness and tone of muscle;
      changes in elasticity were independent of the dose in old animals. In old rats,
      the muscle's viscoelastic properties decreased after dexamethasone
      administration. Significant correlation was found between changes in muscle
      logarithmic decrement and stiffness (rs = 0.90; P < .05) in old animals.
      CONCLUSIONS: Biomechanical and viscoelastic properties of skeletal muscle
      indicate changes in the main function of muscle during glucocorticoid-induced
      muscle atrophy and are in agreement with changes in hind limb strength. The
      myometric measurements indicate the direction and magnitude of change in muscle
      tissue after different doses of dexamethasone administration easily and quickly.

PMID- 29366490
TI  - Concordance and Reliability of Photogrammetric Protocols for Measuring the
      Cervical Lordosis Angle: A Systematic Review of the Literature.
AB  - OBJECTIVE: The aim of this study was to examine and interpret the concordance,
      accuracy, and reliability of photogrammetric protocols available in the
      literature for evaluating cervical lordosis in an adult population aged 18 to 59
      years. METHODS: A systematic search of 6 electronic databases (MEDLINE via
      PubMed, LILACS, CINAHL, Scopus, ScienceDirect, and Web of Science) located
      studies that assessed the reliability and/or concordance and/or accuracy of
      photogrammetric protocols for evaluating cervical lordosis, compared with
      radiography. Articles published through April 2016 were selected. Two independent
      reviewers used a critical appraisal tool (QUADAS and QAREL) to assess the quality
      of the selected studies. RESULTS: Two studies were included in the review and had
      high levels of reliability (intraclass correlation coefficient: 0.974-0.98). Only
      1 study assessed the concordance between the methods, which was calculated using
      Pearson's correlation coefficient. To date, the accuracy of photogrammetry has
      not been investigated thoroughly. CONCLUSION: We encountered no study in the
      literature that investigated the accuracy of photogrammetry in diagnosing
      hyperlordosis of cervical spine. However, both current studies report high levels
      of intra- and interrater reliability. To increase the level of evidence of
      photogrammetry in the evaluation of cervical lordosis, it is necessary to conduct
      further studies using a larger sample to increase the external validity of the
      findings.

PMID- 29366492
TI  - Optimization of large MOD restorations: Composite resin inlays vs. short fiber
      reinforced direct restorations.
AB  - OBJECTIVE: To compare mechanical performance and enamel-crack propensity of
      direct, semi-direct, and CAD/CAM approaches for large MOD composite-resin
      restorations. METHODS: 45 extracted maxillary molars underwent standardized slot
      type preparation (5-mm depth and bucco-palatal width) including immediate dentin
      sealing (Optibond FL) for the inlays (30 teeth). Short-fiber reinforced composite
      resin (EverX Posterior covered by Gradia Direct Posterior) was used for the
      direct approach, Gradia Direct Posterior for the semi-direct, and Cerasmart
      composite resin blocks for CAD/CAM inlays. All inlays were adhesively luted with
      light-curing composite-resin (preheated Gradia Direct Posterior). Shrinkage
      induced enamel cracks were tracked by transillumination photography. Cyclic axial
      isometric chewing (5-Hz) was simulated, starting with a load of 200N (5000
      cycles), followed by stages of 400, 600, 800, 1000, 1200, and 1400N (maximum
      30,000 cycles each) until fracture or to a maximum of 185,000 cycles. Survived
      specimens were subjected to cyclic-load-to-failure test at 30-degree angle on the
      palatal cusp. RESULTS: Only small shrinkage-induced cracks were found in 47% of
      the direct restorations compared to 7% and 13% of semi-direct and CAD/CAM inlays,
      respectively. Survival to accelerated fatigue was similar for all three groups
      (Kaplan-Meier p>.05) and ranged between 87% (direct) and 93% (semi-direct and
      CAD/CAM). Cyclic-load-to-failure tests did not yield significant differences
      either (Life Table analysis, p>.05) with median values of 1675N for CAD/CAM
      inlays, 1775N for fiber-reinforced direct restorations and 1900N for semi-direct
      inlays. SIGNIFICANCE: All three restorative techniques yielded excellent
      mechanical performance above physiological masticatory loads. Direct restorations
      performed as good as inlays when a short-fiber reinforced composite-resin base
      was used.

PMID- 29366491
TI  - Focal epilepsy as the revealing symptom of 5,10-methylenetetrahydrofolate
      reductase deficiency in a young adult.

PMID- 29366493
TI  - Mechanical properties and fracture behavior of flowable fiber reinforced
      composite restorations.
AB  - OBJECTIVE: The aim was to evaluate the effect of short glass-fiber/filler
      particles proportion on fracture toughness (FT) and flexural strength (FS) of an
      experimental flowable fiber-reinforced composite (Exp-SFRC) with two methacrylate
      resin formulations. In addition, we wanted to investigate how the fracture
      behavior of composite restorations affected by FT values of SFRC-substructure.
      METHODS: Exp-SFRC was prepared by mixing 50wt% of dimethacrylate based resin
      matrix (bisGMA or UDMA based) to 50wt% of various weight fractions of glass
      fiber/particulate filler (0:50, 10:40, 20:30, 30:20, 40:10, 50:0wt%,
      respectively). FT and FS were determined for each experimental material following
      standards. Specimens (n=8) were dry stored (37 degrees C for 2 days) before they
      were tested. Four groups of posterior composite crowns (n=6) composed of
      different Exp-SFRCs as substructure and surface layer of commercial particulate
      filler composite were fabricated. Crowns were statically loaded until fracture.
      Failure modes were visually examined. The results were statistically analysed
      using ANOVA followed by post hoc Tukey's test. RESULTS: ANOVA revealed that ratio
      of glass-fiber/particulate filler had significant effect (p<0.05) on tested
      mechanical properties of the Exp-SFRC with both monomer systems. Exp-SFRC (50wt%)
      had significantly higher FT (2.6MPam1/2) and FS (175.5MPa) (p<0.05) compared to
      non-reinforced material (1.3MPam1/2, 123MPa). Failure mode analysis of crown
      restorations revealed that FT value of the substructure directly influenced the
      failure mode. SIGNIFICANCE: This study shows that short glass-fibers can
      significantly reinforce flowable composite resin and the FT value of SFRC
      substructure has prior importance, as it influences the crack arresting
      mechanism.

PMID- 29366494
TI  - Proposal for an algorithm for the management of the patient's airway after smoke
      inhalation.
AB  - Smoke inhalation represents the leading cause of mortality and morbidity in burns
      patients. Given the injuries that can occur in the airway after this exposure, it
      is imperative to evaluate the need for orotracheal intubation in the emergency
      department and even in the place of first assistance by healthcare workers. Since
      the clinical signs are poor predictors of the severity of the lesion, in selected
      cases, it is advisable to perform a diagnostic fibroscopy. We present a case
      report of a patient with a smoke inhalation lesion in which the fibroscopy was
      determinant to proceed to intubation, and we propose an algorithm of action for
      the management of the airway in this type of patients.

PMID- 29366495
TI  - Cerebral oximetry monitoring in the management of severe hypoxaemia associated
      with transposition of the great arteries with balloon atrial septostomy.
AB  - Transposition of the great arteries (D-TGA) is one of the most common congenital
      heart diseases requiring neonatal surgical intervention. In the desperately ill
      neonate with TGA and the resultant hypoxaemia, acidemia, and congestive heart
      failure, improvement is often obtained with balloon atrial septostomy (BAS).
      Current methods employed to evaluate oxygen delivery and tissue consumption are
      frequently nonspecific. Near infrared spectroscopy (NIRS) allows a continuous non
      invasive measurement of tissue oxygenation which reflects perfusion status in
      real time. Because little is known about the direct effect of BAS on the neonatal
      brain and on cerebral oxygenation, we measured the effectiveness of BAS in two
      patients with D-TGA using NIRS before and after BAS. We concluded BAS improves
      cerebral oxygen saturation in neonates with D-TGA.

PMID- 29366496
TI  - Normal values of the ventricular gradient and QRS-T angle, derived from the
      pediatric electrocardiogram.
AB  - BACKGROUND: Normal values of the mathematically-synthesized vectorcardiogram
      (VCG) are lacking for children. Therefore, the objective of this study was to
      assess normal values of the pediatric synthesized VCG (spatial QRS-T angle [SA]
      and ventricular gradient [VG]). METHODS: Electrocardiograms (ECGs) of 1263
      subjects (0-24 years) with a normal heart were retrospectively selected. VCGs
      were synthesized by the Kors matrix. Normal values (presented as 2nd and 98th
      percentiles) were assessed by quantile regression with smoothing by splines.
      RESULTS: Our results show that heart rate decreased over age, QRS duration
      increased and QTc interval remained constant. The SA initially decreased and
      increased again from the age of 8 years. The VG magnitude was relatively stable
      until the age of 2 years, after which it increased. CONCLUSION: Normal values of
      the pediatric ECG and VCG (VG and SA) were established. These normal values could
      be important for future studies using VG and SA for risk stratification in heart
      disease in children.

PMID- 29366497
TI  - PCSK9 inhibitors in clinical practice: Expectations and reality.

PMID- 29366498
TI  - Stroke outcome is associated with baseline renal function: A risk factor that
      matters!

PMID- 29366499
TI  - [Europe and Japan alliance for clinical research in oncology].

PMID- 29366500
TI  - A comprehensive toolkit for imaging children who may have been abused: new
      guidance from the Royal College of Radiologists and the Society and College of
      Radiographers.

PMID- 29366501
TI  - [Muscle pain and statin, pharmacological or nocebo effect?]

PMID- 29366502
TI  - Treatment of type 2 diabetes mellitus in elderly patients.
AB  - The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age.
      Antidiabetic treatment and the objectives of glycaemic control in elderly
      patients with DM2 should be individualised according to their biopsychosocial
      characteristics. In elderly patients for whom the benefits of intensive
      antidiabetic treatment are limited, the basic objectives should be to improve the
      quality of life, preserve functionality and avoid adverse effects, especially
      hypoglycaemia. Treatment of DM2 in the elderly was the subject of a consensus
      document published in 2012 and endorsed by several Spanish scientific societies.
      Since then, new therapeutic groups and evidence have emerged that warrant an
      update to this consensus document. The present document focuses on the
      therapeutic aspects of DM2 in elderly patients, understood as being older than 75
      years or frail.

PMID- 29366503
TI  - Enhancing the chemical selectivity in discovery-based analysis with tandem
      ionization time-of-flight mass spectrometry detection for comprehensive two
      dimensional gas chromatography.
AB  - The complementary information provided by tandem ionization time-of-flight mass
      spectrometry (TI-TOFMS) is investigated for comparative discovery-based analysis,
      when coupled with comprehensive two-dimensional gas chromatography (GC * GC). The
      TI conditions implemented were a hard ionization energy (70 eV) concurrently
      collected with a soft ionization energy (14 eV). Tile-based Fisher ratio (F
      ratio) analysis is used to analyze diesel fuel spiked with twelve analytes at a
      nominal concentration of 50 ppm. F-ratio analysis is a supervised discovery-based
      technique that compares two different sample classes, in this case spiked and
      unspiked diesel, to reduce the complex GC * GC-TI-TOFMS data into a hit list of
      class distinguishing analyte features. Hit lists of the 70 eV and 14 eV data
      sets, and the single hit list produced when the two data sets are fused together,
      are all investigated. For the 70 eV hit list, eleven of the twelve analytes were
      found in the top thirteen hits. For the 14 eV hit list, nine of the twelve
      analytes were found in the top nine hits, with the other three analytes either
      not found or well down the hit list. As expected, the F-ratios per m/z used to
      calculate each average F-ratio per hit were generally smaller fragment ions for
      the 70 eV data set, while the larger fragment ions were emphasized in the 14 eV
      data set, supporting the notion that complementary information was provided. The
      discovery rate was improved when F-ratio analysis was performed on the fused data
      sets resulted in eleven of the twelve analytes being at the top of the single hit
      list. Using PARAFAC, analytes that were "discovered" were deconvoluted in order
      to obtain their identification via match values (MV). Location of the analytes
      and the "F-ratio spectra" obtained from F-ratio analysis were used to guide the
      deconvolution. Eight of the twelve analytes where successfully deconvoluted and
      identified using the in-house library for the 70 eV data set. PARAFAC
      deconvolution of the two separate data sets provided increased confidence in
      identification of "discovered" analytes. Herein, we explore the limit of analyte
      discovery and limit of analyte identification, and demonstrate a general workflow
      for the investigation of key chemical features in complex samples.

PMID- 29366504
TI  - Diagnostic imaging in neuro-ophthalmology.
AB  - Neuro-ophthalmology is a field combining neurology and ophthalmology that studies
      diseases that affect the visual system and the mechanisms that control eye
      movement and pupil function. Imaging tests make it possible to thoroughly assess
      the relevant anatomy and disease of the structures that make up the visual
      pathway, the nerves that control eye and pupil movement, and the orbital
      structures themselves. This article is divided into three sections (review of the
      anatomy, appropriate imaging techniques, and evaluation of disease according to
      clinical symptoms), with the aim of providing useful tools that will enable
      radiologists to choose the best imaging technique for the differential diagnosis
      of patients' problems to reach the correct diagnosis of their disease.

PMID- 29366505
TI  - Letter to the Editor.

PMID- 29366506
TI  - Pediatric surgeon density in South Africa.
AB  - BACKGROUND: There are limited data regarding the available pediatric surgical
      workforce in South Africa and their employment prospects on completion of their
      specialist training. METHODS: This aim of this study was to quantify and analyze
      the pediatric surgical workforce in South Africa as well as to determine their
      geographic and sector distribution. This involved a quantitative descriptive
      analysis of all registered specialist as well as training pediatric surgeons in
      South Africa. RESULTS: The results showed 2.6 pediatric surgeons per one million
      population under 14 years. More than half (69%) were male and the median age was
      46.8 years. There were however, more female surgical registrars currently in
      training. The majority of the pediatric surgical practitioners were found in
      Gauteng, followed by the Western Cape and Kwa-Zulu Natal. The majority of
      specialists reportedly worked in the public sector, however the number of public
      sector pediatric surgeons available to those without health insurance fell below
      those available to private patients. CONCLUSION: Interprovincial differences as
      well as intersectoral differences were marked indicating geographic and
      socioeconomic maldistribution of pediatric surgeons. Addressing this
      maldistribution requires concerted efforts to expand public sector specialist
      posts. STUDY TYPE: Descriptive audit LEVEL OF EVIDENCE: IV.

PMID- 29366507
TI  - Decentralized adaptive control of interconnected nonlinear systems with unknown
      control directions.
AB  - In this paper, we propose a decentralized adaptive control scheme for a class of
      interconnected strict-feedback nonlinear systems without a priori knowledge of
      subsystems' control directions. To address this problem, a novel Nussbaum-type
      function is proposed and a key theorem is drawn which involves quantifying the
      interconnections of multiple Nussbaum-type functions of the subsystems with
      different control directions in a single inequality. Global stability of the
      closed-loop system and asymptotic stabilization of subsystems' output are proved
      and a simulation example is given to illustrate the effectiveness of the proposed
      control scheme.

PMID- 29366508
TI  - High-speed, high-precision focal length measurement using double-hole mask and
      advanced image sensor software.
AB  - A cutting-edge precision technique for computation of focal length of a positive
      lens with double-hole mask is described. The technique is simple and versatile
      due to incorporation of the updated functions of image sensor device that
      supports reading the distance between beam spots instantaneously while the
      position of the specimen is being changed, as well as the reduction in several
      challenging measurement steps. Furthermore, this technique does not require prior
      knowledge of distances in the optical setup. High accuracy in focal-length
      measurement is obtained by precise beam spot distance analysis using image sensor
      integrated software. The acquired data exhibit considerably high precision and
      reproducibility.

PMID- 29366509
TI  - SLN biopsy in cervical cancer patients with tumors larger than 2cm and 4cm.
AB  - OBJECTIVES: The aim of this study was to assess the detection rate, false
      negative rate and sensitivity of SLN in LN staging in tumors over 2cm on a large
      cohort of patients. METHODS: Data from patients with stages pT1a - pT2 cervical
      cancer who underwent surgical treatment, including SLN biopsy followed by
      systematic pelvic lymphadenectomy, were retrospectively analyzed. A combined
      technique with blue dye and radiocolloid was modified in larger tumors to inject
      the tracer into the residual cervical stroma. RESULTS: The study included 350
      patients with stages pT1a - pT2. Macrometastases, micrometastases, and isolated
      tumor cells were found in 10%, 8%, and 4% of cases. Bilateral detection rate was
      similar in subgroups with tumors<2cm, 2-3.9cm, and >=4cm (79%, 83%, 76%)
      (P=0.460). There were only two cases with false-negative SLN ultrastaging for
      pelvic LN status among those with bilateral SLN detection. The false negative
      rate was very low in all three subgroups of different tumor sizes (0.9%, 0.9%,
      and 0.0%; P=0.999). Sensitivity reached 96% in the whole group and was high in
      all three groups (93%, 93%, 100%; P=0.510). CONCLUSIONS: If the tracer
      application technique is adjusted in larger tumors, SLN biopsy can be equally
      reliable in pelvic LN staging in tumors smaller and larger than 2cm. The
      bilateral detection rate and false negative rate did not differ in subgroups of
      patients with tumors<2cm, 2-3.9cm, and >=4cm.

PMID- 29366510
TI  - The NCI-MATCH trial and precision medicine in gynecologic cancers.
AB  - The Precision Medicine Initiative is a National Cancer Institute (NCI) driven
      interdisciplinary collaborative effort to test the feasibility of trials
      incorporating genomic profiling when choosing patient therapies. The goal of the
      initiative is to generate the scientific evidence needed to move the concept of
      precision medicine, or targeted therapy, into clinical practice. The rapid
      development and widespread availability of next generation sequencing provides
      access to information regarding an individual's tumor at various times during the
      course of their disease. Translating the aberrations specific to a patient's
      tumor into personalized treatment is the concept behind "basket" trials, and thus
      categorize patients' cancers based on the sequencing of the tumor, rather than
      the organ of origin. The NCI Molecular Analysis for Therapy Choice (MATCH) trial
      [NCT02465060] is a multi-site, collaborative effort between the NCI and several
      pharmaceutical companies that is beginning to clarify the significance of
      molecular alterations in tumors. This trial was designed to assign targeted
      treatment based on molecular alterations identified from a tumor biopsy obtained
      after study enrollment and determine the efficacy of this treatment. This review
      article will briefly discuss known genomic aberrations in gynecologic cancers,
      and then provide an overview of the NCI-MATCH trial with an update on accrual and
      recent interim analysis. We will also review current FDA-approved precision
      therapies for gynecologic malignancies, such as poly (ADP ribose) polymerase
      (PARP) inhibitors.

PMID- 29366511
TI  - A systematic review and meta-analysis of psychological functioning in chronic
      tinnitus.
AB  - Chronic tinnitus, the phenomenon of a chronic ringing in the ears or head, has a
      significant negative impact on an individual's health and wellbeing. Despite
      this, there is no cure or consensus regarding factors maintaining ongoing
      awareness of the sensation in this population, or the severity of its impact. We
      aimed to comprehensively and systematically review behavioural studies
      investigating the psychological functioning of adults with chronic tinnitus. We
      identified 64 papers meeting our search criteria for inclusion, which are
      reviewed with regard to psychological factors involved with the presence of
      chronic tinnitus, and those relating to its severity. The majority of studies
      assessed the presence and impact of chronic tinnitus with regard to emotional
      wellbeing (n=59), with a more recent interest in cognitive functioning (n=16). A
      subset of 36 studies was included in meta-analyses investigating the
      relationships between emotional wellbeing and the presence and impact of chronic
      tinnitus using random-effects models. Our findings indicate the presence of
      chronic tinnitus may be associated with reduced cognitive functioning,
      particularly attention, and with reduced emotional wellbeing, particularly
      anxiety and depression. We also found consistent evidence indicating severity of
      chronic tinnitus is associated with a broad range of psychological features,
      primarily symptoms of depression and anxiety. We recommend investigating the
      complexity of the relationships between emotional wellbeing, cognitive
      functioning, and chronic tinnitus using a range of methodologies to further
      elucidate the role of psychological functioning in chronic tinnitus.

PMID- 29366512
TI  - Risky business: Changes in boldness behavior in male Siamese fighting fish, Betta
      splendens, following exposure to an antiandrogen.
AB  - Components of boldness, such as activity level and locomotion, influence an
      individual's ability to avoid predators and acquire resources, generating fitness
      consequences. The presence of endocrine disrupting chemicals (EDCs) in the
      aquatic environment may affect fitness by changing morphology or altering
      behaviors like courtship and exploration. Most research on EDC-generated
      behavioral effects has focused on estrogen mimics and reproductive endpoints. Far
      fewer studies have examined the effects of other types of EDCs or measured non
      reproductive behaviors. EDCs with antiandrogenic properties are present in
      waterways yet we know little about their effects on exposed individuals although
      they may produce effects similar to those caused by estrogen mimics because they
      act on the same hormonal pathway. To examine the effects of antiandrogens on
      boldness, this study exposed male Siamese fighting fish, Betta splendens, to a
      high or low dose of one of two antiandrogens, vinclozolin or flutamide, and
      observed behavior in three boldness assays, both before and after exposure.
      Overall, antiandrogen exposure increased boldness behavior, especially following
      exposure to the higher dose. Whether or not antiandrogen exposure influenced
      boldness, as well as the nature and intensity of the effect, was assay-dependent.
      This demonstrates the importance of studying EDC effects in a range of contexts
      and, at least within this species, suggests that antiandrogenic compounds may
      generate distinct physiological effects in different situations. How and why the
      behavioral effects differ from those caused by exposure to an estrogen mimic, as
      well as the potential consequences of increased activity levels, are discussed.
      Exposure to an antiandrogen, regardless of dose, produced elevated activity
      levels and altered shoaling and exploration in male Siamese fighting fish. These
      modifications may have fitness consequences.

PMID- 29366513
TI  - Vibegron, a Novel Potent and Selective beta3-Adrenoreceptor Agonist, for the
      Treatment of Patients with Overactive Bladder: A Randomized, Double-blind,
      Placebo-controlled Phase 3 Study.
AB  - BACKGROUND: Vibegron is a novel, potent, and selective beta3-adrenoreceptor
      agonist for the treatment of patients with overactive bladder (OAB). OBJECTIVE:
      To evaluate the efficacy and safety of vibegron versus placebo in Japanese OAB
      patients. DESIGN, SETTING, AND PARTICIPANTS: Patients with OAB entered a 2-wk
      placebo run-in phase. Once eligibility (>=8 micturition/d and either >=1 urgency
      episodes/d or >=1 urgency incontinence episodes/d) was confirmed, patients
      entered a 12-wk double-blind treatment phase. The anticholinergic imidafenacin
      was used as an active reference. INTERVENTION: A total of 1232 patients were
      randomly assigned to one of the four 12-wk treatment groups: vibegron (50mg or
      100mg once daily), placebo, or imidafenacin (0.1mg twice daily). OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was change in the
      mean number of micturitions/d at wk 12 from baseline. The secondary endpoints
      were changes from baselines in OAB symptom variables (daily episodes of urgency,
      urgency incontinence, incontinence, and nocturia, and voided volume/micturition).
      Quality of life (QoL) and safety were assessed. A constrained longitudinal data
      analysis model was used for analysis of efficacy. RESULTS AND LIMITATIONS:
      Patients taking vibegron 50mg and 100mg orally for 12 wk had significant
      improvements over the placebo in the primary and secondary endpoints. The
      proportions of patients with normalization of micturition, resolution of urgency,
      urgency incontinence, and incontinence were significantly greater than placebo.
      Vibegron significantly improved QoL, with high patient satisfaction. Incidences
      of drug-related adverse events with vibegron 50mg and 100mg were 7.6%, 5.4%,
      similar to placebo (5.1%), and less than imidafenacin (10.3%). Treatment was for
      just 12 wk and a long-term study is needed. CONCLUSIONS: The 12-wk treatment with
      vibegron is effective and well tolerated in patients with OAB. PATIENT SUMMARY:
      This randomized study demonstrated that vibegron is clinically useful for
      treatment of patients with OAB. Trial registration JapicCTI-152936.
      http://www.clinicaltrials.jp/user/cteDetail.jsp.

PMID- 29366514
TI  - Cognitive determinants of healthcare evaluations - A comparison of Eastern and
      Western European countries.
AB  - Knowing the public opinion of healthcare is essential when assessing healthcare
      system performance; but little research has focussed on the links between the
      public's general attitude to the healthcare system and its perceptions and
      expectations of specific healthcare-related aspects. Using data from the fourth
      round of the European Social Survey 2008/09, we explore the cognitive
      determinants of global evaluations of the healthcare system in 12 Eastern and 16
      Western European countries. We find that healthcare evaluations follow a coherent
      cognitive reasoning. They are associated with (i) perceptions of the performance
      of healthcare systems (i.e. efficiency, equality of treatment, health outcomes),
      (ii) expectations of the government's role in providing healthcare, and (iii)
      reflections on demographic pressures (i.e. aging populations). Contrary to the
      general assumption that normative expectations are responsible for differences in
      healthcare evaluations between Eastern and Western Europe, our results suggest
      that regional differences are largely due to a more negative perception of the
      performance of healthcare systems within Eastern Europe. To enhance the public
      opinion of healthcare, policy makers should improve the efficiency of healthcare
      systems and take measures to assure equality in health treatment.

PMID- 29366515
TI  - Antinociceptive profiles and mechanisms of centrally administered oxyntomodulin
      in various mouse pain models.
AB  - In the present study, the antinociceptive profiles of oxyntomodulin were examined
      in ICR mice. Oxyntomodulin administered intrathecally (i.t.) and
      intracerebroventricularly (i.c.v.) (from 1 to 5MUg/5MUl) showed an
      antinociceptive effect in a dose-dependent manner as measured in the acetic acid
      induced writhing test. Moreover, cumulative response time of nociceptive
      behaviors induced by intraplantar formalin injection was reduced by i.t. or
      i.c.v. treatment with oxyntomodulin during the second, but not the first phase.
      In addition, the cumulative nociceptive response time after i.t. injection with
      substance P (0.7MUg), glutamate (20MUg), and pro-inflammatory cytokines such as
      TNF-alpha, IL-beta or IFN-gamma (100pg/5MUl) was diminished by spinally or
      supraspinally administered oxyntomodulin. However, i.t. and i.c.v. treatment with
      oxyntomodulin did not affect latencies of the tail-flick and hot-plate paw
      licking responses. Furthermore, the i.t. pretreatment with yohimbine (adrenergic
      receptor antagonist), but not naloxone (an opioid receptor antagonist) or
      methysergide (a serotonergic receptor antagonist), attenuated antinociceptive
      effect induced by oxyntomodulin administered i.c.v. in the writhing test. The
      i.c.v. or i.t. pretreatment with oxyntomodulin attenuated formalin-induced
      increase of phosphorlated ERK (p-ERK) expression in the spinal cord. Our results
      suggest that centrally administered oxyntomodulin shows an antinociceptive
      property in various pain models except for thermal-induced nociception.
      Furthermore, supraspinally administered oxyntomodulin-induced antinociception may
      be mediated by spinal adrenergic receptors, but not serotonergic and opioidergic
      receptors. Furthermore, the antinociception induced by oxyntomodulin appears to
      be mediated by reduced formalin-induced p-ERK expression in the spinal cord.

PMID- 29366516
TI  - Evolving Ecosystems: Inheritance and Selection in the Light of the Microbiome.
AB  - The importance of microorganisms in human biology is undeniable. The amount of
      research that supports that microbes have a fundamental role in animal and plant
      physiology is substantial and increasing every year. Even though we are only
      beginning to comprehend the broadness and complexity of microbial communities,
      evolutionary theories need to be recast in the light of such discoveries to fully
      understand and incorporate the role of microbes in our evolution. Fundamental
      evolutionary concepts such as diversity, heredity, selection, speciation, etc.,
      which constitute the modern synthesis, are now being challenged, or at least
      expanded, by the emerging notion of the holobiont, which defines the genetic and
      metabolic networks of the host and its microbes as a single evolutionary unit.
      Several concepts originally developed to study ecosystems, can be used to
      understand the physiology and evolution of such complex systems that constitute
      "individuals." In this review, we discuss these ecological concepts and also
      provide examples that range from squids, insects and koalas to other mammals and
      humans, suggesting that microorganisms have a fundamental role not only in
      physiology but also in evolution. Current evolutionary theories need to take into
      account the dynamics and interconnectedness of the host-microbiome network, as
      animals and plants not only owe their symbiogenetic origin to microbes, but also
      share a long evolutionary history together.

PMID- 29366517
TI  - Reply Letter to the Editor-Lifestyle predictors of obese and non-obese patients
      with nonalcoholic fatty liver disease: A cross-sectional study.

PMID- 29366518
TI  - Reply-Letter to the Editor-Some notes on citrulline in the CNS.

PMID- 29366519
TI  - Palliative radiotherapy for locally advanced non-metastatic head and neck cancer:
      A survey of UK national practice.

PMID- 29366520
TI  - Clinical significance of soluble programmed cell death ligand-1 (sPD-L1) in
      hepatocellular carcinoma patients treated with radiotherapy.
AB  - PURPOSE: To investigate the clinical implications of the soluble programmed cell
      death-ligand 1 (sPD-L1) level in hepatocellular carcinoma (HCC) patients treated
      with radiotherapy (RT). MATERIALS/METHODS: HCC patients treated with RT between
      June 2011 and March 2015 were prospectively recruited and sPD-L1 levels were
      measured using an enzyme-linked immunosorbent assay. Blood samples were obtained
      at the RT start, RT end, and 1-month follow-up. The associations of the sPD-L1
      level with the clinical features and outcomes were analyzed. RESULTS: Fifty-three
      patients with HCC were included. Thirty-four patients received conventional
      fractionated RT with hepatic arterial infusional chemotherapy, while 19 patients
      received stereotactic body radiotherapy (SBRT). The initial sPD-L1 level was
      significantly associated with stage, tumor size, portal vein tumor thrombosis,
      and venous invasion. The overall-survival was significantly poorer in patients
      with a higher level of initial sPD-L1 (>=1.315 pg/mL). A higher level of sPD-L1
      at 1 month (>=12.9 pg/mL) was significantly related to early lung metastasis. The
      sPD-L1 level was significantly increased after RT and the change pattern of sPD
      L1 was different between two RT schemes. CONCLUSIONS: The level of sPD-L1 was
      associated with tumor aggressiveness and outcomes, suggesting its role as a
      possible predictive biomarker. The increases in sPD-L1 after RT suggests that
      combined treatment with RT and immune checkpoint inhibitors may be a promising
      therapeutic strategy in HCC.

PMID- 29366522
TI  - Personalized Cancer Medicine: An Organoid Approach.
AB  - Personalized cancer therapy applies specific treatments to each patient. Using
      personalized tumor models with similar characteristics to the original tumors may
      result in more accurate predictions of drug responses in patients. Tumor organoid
      models have several advantages over pre-existing models, including conserving the
      molecular and cellular composition of the original tumor. These advantages
      highlight the tremendous potential of tumor organoids in personalized cancer
      therapy, particularly preclinical drug screening and predicting patient responses
      to selected treatment regimens. Here, we highlight the advantages, challenges,
      and translational potential of tumor organoids in personalized cancer therapy and
      focus on gene-drug associations, drug response prediction, and treatment
      selection. Finally, we discuss how microfluidic technology can contribute to
      immunotherapy drug screening in tumor organoids.

PMID- 29366521
TI  - A prospective study of the safety and efficacy of liver stereotactic body
      radiotherapy in patients with and without prior liver-directed therapy.
AB  - BACKGROUND AND PURPOSE: To evaluate the safety and efficacy of liver stereotactic
      body radiotherapy (SBRT), and examine potential factors impacting outcomes
      including prior liver-directed therapy. MATERIALS AND METHODS: Patients with ECOG
      0-1, Child-Pugh Class A or B, and primary hepatocellular carcinoma (HCC) or liver
      metastases unsuitable for surgical resection or ablation were eligible for a
      prospective single arm trial. SBRT was delivered with a CyberKnife system to 45
      Gy in 3 fractions with a predetermined dose de-escalation scheme. Adverse events,
      local control, and survival were assessed. RESULTS: A total of 30 patients were
      enrolled. Eleven patients (37%) had HCC and 19 (63%) patients had liver
      metastases. Fourteen patients (47%) had prior liver-directed therapies including
      nine with liver resection, seven with trans-arterial chemoembolization, and six
      with radiofrequency ablation. Cumulative grade 2 and 3 acute toxicity occurred in
      47% and 7% of patients, respectively. Similar rates of >=grade 2 acute toxicity
      were observed between patients who had prior liver-directed treatments and those
      who did not. At a median follow-up of 12.7 months, 1-year local control and
      overall survival were 81% and 62%, respectively. Prior liver-directed therapy did
      not affect local control or survival. CONCLUSIONS: Liver SBRT is a safe and
      effective treatment even in the setting of prior liver-directed surgical and
      ablative therapies.

PMID- 29366523
TI  - Immunomodulation of allergic response in children and adolescents: What we can
      learn from lymphatic filarial infection.
AB  - BACKGROUND: Although it is well known that allergic diseases involve a strong Th2
      immune response, with production of high levels of specific IgE allergen,
      knowledge on the association between filarial infection and allergies, among
      paediatric patients is scarce. OBJECTIVE: To evaluate the allergic response
      patterns in cases of filarial infection by comparing peripheral eosinophils,
      total IgE levels, immediate hypersensitivity and cytokine levels in children and
      adolescents in Brazil. METHODS: This was an exploratory study with three groups:
      (I) with filarial infection and without allergic diseases; (II) without filarial
      infection and with allergic diseases; and (III) without filarial infection and
      without allergic diseases. The prick test and specific IgE tests for
      aeroallergens were performed using five antigens. Peripheral eosinophils and
      total IgE were also evaluated. IL-4 and IL-5 were determined using whole-blood
      culture stimulated by three antigens. RESULTS: Eosinophilia and elevated levels
      of total IgE (>=400IU/dl) were observed in all groups. The prick test was
      positive in 56.6% of the cases. Group I presented hypersensitive responses
      similar to the allergic disease groups. In the whole-blood culture stimulated by
      Dermatophagoides pteronyssinus, average IL-4 production did not differ
      significantly among the groups, but IL5 production resulting from stimulation was
      greater in the allergic disease groups (p<0.05). CONCLUSIONS: The allergic
      response pattern in group with filarial infection was similar to that of the
      groups with and without allergic diseases, but the response to IL-5 in the
      culture stimulated by D. pteronyssinus was an exclusive characteristic of the
      allergic group.

PMID- 29366525
TI  - Mice over-expressing placenta growth factor in the skin exhibit increased
      vascularization and vessel permeability independently of VEGF-A.

PMID- 29366524
TI  - Associations between maternal phenol and paraben urinary biomarkers and maternal
      hormones during pregnancy: A repeated measures study.
AB  - BACKGROUND: A number of phenols and parabens are added to consumer products for a
      variety of functions, and have been found at detectable levels in the majority of
      the U.S. POPULATION: Among other functions, thyroid hormones are essential in
      fetal neurodevelopment, and could be impacted by the endocrine disrupting effects
      of phenols and parabens. The present study investigated the association between
      ten maternal urinary phenol and paraben biomarkers (bisphenol S, triclosan,
      triclocarban, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and ethyl,
      butyl, methyl and propyl paraben) and four plasma thyroid hormones in 439
      pregnant women in a case-control sample nested within a cohort study based in
      Boston, MA. METHODS: Urine and blood samples were collected from up to four
      visits during pregnancy (median weeks of gestation at each visit: Visit 1: 9.64,
      Visit 2: 17.9, Visit 3: 26.0, Visit 4: 35.1). Linear mixed models were
      constructed to take into account the repeated measures jointly, followed by
      multivariate linear regression models stratified by gestational age to explore
      potential windows of susceptibility. RESULTS: We observed decreased total
      triiodothyronine (T3) in relation to an IQR increase in benzophenone-3 (percent
      change [%Delta] = -2.07; 95% confidence interval [CI] = -4.16, 0.01), butyl
      paraben (%Delta = -2.76; 95% CI = -5.25, -0.26) and triclosan (%Delta = -2.53;
      95% CI = -4.75, -0.30), and triclocarban at levels above the LOD (%Delta = -5.71;
      95% CI = -10.45, -0.97). A 2.41% increase in T3 was associated with an IQR
      increase in methyl paraben (95% CI = 0.58, 4.24). We also detected a negative
      association between free thyroxine (FT4) and propyl paraben (%Delta = -3.14; 95%
      CI = -6.12, -0.06), and a suggestive positive association between total thyroxine
      (T4) and methyl paraben (%Delta = 1.19; 95% CI = -0.10, 2.47). Gestational age
      specific multivariate regression analyses showed that the magnitude and direction
      of some of the observed associations were dependent on the timing of exposure.
      CONCLUSION: Certain phenols and parabens were associated with altered thyroid
      hormone levels during pregnancy, and the timing of exposure influenced the
      association between phenol and paraben, and hormone concentrations. These changes
      may contribute to downstream maternal and fetal health outcomes. Additional
      research is required to replicate the associations, and determine the potential
      biological mechanisms underlying the observed associations.

PMID- 29366526
TI  - Use of intralesional blood to determine diffusible biomarkers from skin lesions.
AB  - BACKGROUND: Biomarkers provide beneficial information to make diagnoses and
      monitor the progression of many skin diseases. However, biomarkers produced by
      skin lesion may be too low at concentration to be detected in the systemic
      circulation. OBJECTIVE: To address whether intralesional blood (ILB) is
      advantageous to detect skin-derived biomarkers over circulation blood (CB) of
      patients with skin diseases. METHODS: ILB was collected as overflowing blood when
      a small incision was made in lesions of patients with mastocytoma and psoriasis.
      Concentrations of histamine and Human beta-Defensin 2 were determined by ELISA.
      IL-8 was measured using a cytometric beads array (CBA) kit. IL-8 levels in
      psoriatic lesions were assessed by immunohistochemical staining and quantitative
      (q) RT-PCR. MicroRNA levels were measured using qRT-PCR. RESULTS: Plasma
      histamine levels were increased in ILB of mastocytoma compared with those in CB.
      Patients with psoriasis showed increased levels of IL-8, beta-Defensin 2 in ILB
      as compared to those in CB. IL-8 levels in ILB correlated with local PASI scores
      and therefore reversed to those in CB after attenuation of psoriasis with
      treatment. Furthermore, ILB in psoriasis patients showed increased miR-203, which
      was highly expressed in psoriatic epidermis. CONCLUSION: ILB contains disease
      specific biomarkers at higher concentrations than those in CB, and may be useful
      for diagnosis and monitoring the progression of skin diseases. Thus, this study
      illustrates the versatility of ILB with an easy accessibility of biomarkers of
      chemicals, proteins as well as nucleic acids for a myriad of diseases including
      inflammatory dermatoses and cancers.

PMID- 29366528
TI  - Corrigendum to "Prescription drug monitoring program utilization among 15 US
      opioid treatment programs" [J. Subst. Abus. Treat. 85 (2018) 17-20].

PMID- 29366527
TI  - Translation and Psychometric Analysis of the Chinese Version of the Dutch Eating
      Behavior Questionnaire for Children (DEBQ-C) in Taiwanese Preadolescents.
AB  - PURPOSE: This study aimed to translate and evaluate the psychometric properties
      of a Chinese version of the (DEBQ-C) among Taiwanese preadolescents. DESIGN AND
      METHODS: The DEBQ-C was translated into Mandarin Chinese (CDEBQ-C) using
      established translation and back-translation methods and reviewed by an expert
      panel for cultural equivalence. A convenience sample of 349 preadolescents was
      randomly split to conduct exploratory factor analysis (EFA) on the first half and
      confirmatory factor analysis (CFA) on the second. Internal consistency estimates
      for subscales were evaluated using Cronbach's alpha. Construct validation with
      academic stress, a theoretically related construct, was also examined. RESULTS:
      The theoretical dimensions of the original DEBQ-C were supported with an EFA that
      revealed the presence of three factors with 41.23% variance explained, and model
      fit was confirmed by CFA. Construct validation was supported by positive
      correlations with academic stress. Each subscale of the CDEBQ-C demonstrated
      satisfactory internal consistency (Cronbach's alpha = 0.72-0.86).
      Overweight/obese preadolescents scored significantly higher on restrained eating
      compared to other weight groups. CONCLUSIONS: The findings suggest that the CDEBQ
      C is a psychometrically valid and reliable instrument for assessing overeating
      tendencies with Taiwanese preadolescents. Replication studies with greater
      diversity in age, ethnicity, and weight are needed to provide further evidence of
      construct validity for the CDEBQ-C. PRACTICE IMPLICATIONS: Clinicians and
      researchers can use the CDEBQ-C to assess or expand the knowledge of children's
      overeating. At-risk preadolescents can be identified at an early stage and
      effective and individualized intervention programs may be designed and
      facilitated.

PMID- 29366529
TI  - Use of medial upper arm free flap in oral cavity reconstruction: a preliminary
      study.
AB  - The medial upper arm has previously been proposed as a potential free flap donor
      site, but the clinical application of such flaps in head and neck reconstruction
      has not been popular. The preliminary results of the clinical application of
      medial upper arm free flaps in oral cavity reconstruction are reported here. Five
      patients with oral cancer underwent surgical resection and neck dissection, with
      simultaneous reconstruction using a medial upper arm free flap. Functional
      outcomes were investigated using the University of Washington Quality of Life
      Questionnaire. Sensory-motor functions of the upper arm donor site were recorded
      before and after surgery. Four flaps were successfully transferred. One flap was
      abandoned during surgery because of a lack of perforators, and a forearm flap was
      used instead. All patients survived without loco-regional recurrence or distant
      metastasis. Functional outcomes, especially swallowing and speech, were
      satisfactory. The donor site scar was well hidden, with no functional impairment.
      This initial experience shows that the medial upper arm free flap represents an
      alternative perforator flap for oral cavity microsurgical reconstruction. The
      well-hidden scar and better texture match compared with other flaps make it
      suitable for oral cavity reconstruction.

PMID- 29366530
TI  - Identification and characterization of long non-coding RNA in prenatal and
      postnatal skeletal muscle of sheep.
AB  - lncRNAs are a class of transcriptional RNA molecules of >200 nucleotides in
      length. However, the overall expression pattern and function of lncRNAs in sheep
      muscle is not clear. Here, we identified 1566 lncRNAs and 404 differentially
      expressed lncRNAs in sheep muscle from prenatal (110 days of fetus) and postnatal
      (2 to 3 years old of adult sheep) developmental stages by using RNA-seq
      technology. Several lncRNAs were identified by using RT-PCR and DNA sequencing.
      The expression levels of several lncRNAs were confirmed by qRT-PCR. We analyzed
      the effect of lncRNAs that act cis to the target genes. lncRNA targeting genes
      were involved in signaling pathways associated with growth and development of
      muscle by GO and KEGG enrichment analysis. Through our study, we provide a
      comprehensive expression profile of muscle lncRNAs in sheep, which provides
      valuable resources for further understanding genetic regulation of muscle growth
      and development from the perspective of lncRNA.

PMID- 29366531
TI  - [Transmission of death certificates to CepiDc-Inserm related to suspicious
      deaths, in France, since 2000].
AB  - BACKGROUND: The purpose of this study is to assess variability in death
      certificates' transmission related to suspicious deaths. METHODS: The medical
      part of death certificates of suspicious deaths (violent or sudden deaths,
      unknown or ill-defined causes of death) were examined. We studied the frequency
      of suspicious deaths, in France, for deaths aged under 65, from 2000 to 2013,
      searching for temporal (2000-2013) and spatial correlations between unknown
      causes of death and other suspicious causes, and report of an autopsy. These
      results were compared with external data. RESULTS: Standardized proportion of
      deaths by unknown cause more than doubled during the study period (from 3.4 to
      7.5%). The spatial correlation was strongly negative between standardized
      proportions of unknown causes of death and violent deaths (ICC=-0.80). Report of
      autopsy varied with cause of suspicious death and estimated zone of the forensic
      institute. The distribution was consistently distributed with external data,
      except for homicides. CONCLUSION: Information transmission to CepiDc-Inserm needs
      to be improved in case of suspicious death, in particularly from forensic
      institutes. This study emphasizes the urgent need for a complementary form to the
      death certificate.

PMID- 29366532
TI  - Anytime multipurpose emotion recognition from EEG data using a Liquid State
      Machine based framework.
AB  - Recent technological advances in machine learning offer the possibility of
      decoding complex datasets and discern latent patterns. In this study, we adopt
      Liquid State Machines (LSM) to recognize the emotional state of an individual
      based on EEG data. LSM were applied to a previously validated EEG dataset where
      subjects view a battery of emotional film clips and then rate their degree of
      emotion during each film based on valence, arousal, and liking levels. We
      introduce LSM as a model for an automatic feature extraction and prediction from
      raw EEG with potential extension to a wider range of applications. We also
      elaborate on how to exploit the separation property in LSM to build a
      multipurpose and anytime recognition framework, where we used one trained model
      to predict valence, arousal and liking levels at different durations of the
      input. Our simulations showed that the LSM-based framework achieve outstanding
      results in comparison with other works using different emotion prediction
      scenarios with cross validation.

PMID- 29366533
TI  - Children and screens: Groupe de Pediatrie Generale (Societe francaise de
      pediatrie) guidelines for pediatricians and families.
AB  - The Groupe de Pediatrie Generale (General Pediatrics Group), a member of the
      Societe francaise de pediatrie (French Pediatrics Society), has proposed
      guidelines for families and doctors regarding children's use of digital screens.
      A number of guidelines have already been published, in particular by the French
      Academy of Sciences in 2013 and the American Academy of Pediatrics in 2016. These
      new guidelines were preceded by an investigation into the location of digital
      screen use by young children in France, a survey of medical concerns on the
      misuse of digital devices, and a review of their documented benefits. The Conseil
      Superieur de l'Audiovisuel (Higher Council on Audiovisual Technology) and the
      Union Nationale de Associations Familiales (National Union of Family
      Associations) have taken part in the preparation of this document. Five simple
      messages are proposed: understanding without demonizing; screen use in common
      living areas, but not in bedrooms; preserve time with no digital devices
      (morning, meals, sleep, etc.); provide parental guidance for screen use; and
      prevent social isolation.

PMID- 29366534
TI  - WASP (Write a Scientific Paper) using Excel - 3: Plotting data.
AB  - The plotting of data into graphs should be a mandatory step in all data analysis
      as part of a descriptive statistics exercise, since it gives the researcher an
      overview of the shape and nature of the data. Moreover, outlier values may be
      identified, which may be incorrect data, or true outliers, from which important
      findings (and publications) may arise. This exercise should always precede
      inferential statistics, when possible, and this paper in the Early Human
      Development WASP series provides some pointers for doing so in Microsoft ExcelTM.

PMID- 29366535
TI  - Corrigendum to "Long range molecular dynamics study of interactions of the
      eukaryotic glucosamine-6-phosphate synthase with fructose-6-phosphate and UDP
      GlcNAc" [J. Mol. Graph. Model. 78 (2017) 14-25].

PMID- 29366536
TI  - Transient benign paroxysmal movement disorders in infancy.
AB  - This review summarizes the current empirical and clinical literature on benign
      paroxysmal movement disorders in infancy most relevant to practitioners.
      Paroxysmal benign movement disorders are a heterogeneous group of movement
      disorders characterized by their favourable outcome. We pay special attention to
      the recognition and management of these abnormal motor conditions strongly
      suggestive of epileptic disorders. They include: neonatal jitteriness; benign
      neonatal sleep myoclonus; benign paroxysmal tonic upgaze; paroxysmal tonic
      downgaze, benign paroxysmal torticollis and benign polymorphous movement disorder
      of infancy.

PMID- 29366537
TI  - Circulating and urinary microRNAs as possible biomarkers in kidney
      transplantation.

PMID- 29366538
TI  - Incidence and risk factors for epidural re-siting in parturients with
      breakthrough pain during labour epidural analgesia: a cohort study.
AB  - INTRODUCTION: Epidural re-siting is one of the significant events during labour
      epidural analgesia that may result in decreased patient satisfaction. The aim of
      our study was to investigate the incidence of and factors associated with
      epidural re-siting in parturients using epidural analgesia, with an emphasis on
      those with breakthrough pain. METHODS: A retrospective cohort study of 10170
      parturients who received labour epidural analgesia. The primary outcome was the
      incidence of epidural re-siting (binary data). Univariate and multivariate
      logistic regression analysis were performed to find associated risk factors for
      re-siting. RESULTS: Less than 1% (0.85%, 86/10170) of the women in the study had
      their epidural re-sited. Amongst the subset of women with breakthrough pain, the
      incidence of epidural re-siting was higher (4.7%, 68/1454). Most of the women who
      had their epidural re-sited had experienced breakthrough pain (79%, 68/86).
      Amongst all parturients, the presence of breakthrough pain (OR=21.31),
      hypotension (OR=4.18) and venous puncture (OR=2.74) were significantly associated
      with re-siting. Amongst the parturients with breakthrough pain who required
      epidural re-siting, lower cervical dilatation (OR=0.81), higher number of
      episodes of breakthrough pain (OR=1.83) and patchy block (OR=4.37) were
      significantly associated with re-siting. The areas-under-curves of two
      multivariate models were 0.894 and 0.806 respectively. CONCLUSION: In our
      institution, the incidence of epidural catheter re-siting was low in all
      patients. However, the majority of patients whose catheters were re-sited had
      exhibited breakthrough pain. The risk factors associated with the need for re
      siting of catheters in all patients differed from those who had breakthrough
      pain.

PMID- 29366539
TI  - Epigenetic mechanisms in coronary artery disease: The current state and
      prospects.
AB  - Coronary artery disease (CAD) is the leading cause of morbidity and mortality.
      CAD has both genetic and environmental causes. In the past two decades, the
      understanding of epigenetics has advanced swiftly and vigorously. It has been
      demonstrated that epigenetic modifications are associated with the onset and
      progression of CAD. This review aims to improve the understanding of the
      epigenetic mechanisms closely related to CAD and to provide a novel perspective
      on the onset and development of CAD. Epigenetic changes include DNA methylation,
      histone modification, microRNA and lncRNA, which are interrelated with critical
      genes and influence the expression of those genes. In addition, miRNA plays a
      diverse role in the pathological process of CAD. Numerous studies have found that
      some cardiac-specific miRNAs have potential as certain diagnostic biomarkers and
      treatment targets for CAD. In this review, the aberrant epigenetic mechanisms
      that contribute to CAD will be discussed. We will also provide novel insight into
      the epigenetic mechanisms that target CAD.

PMID- 29366540
TI  - Anatomy of Master Knot of Henry: A morphometric study on cadavers.
AB  - OBJECTIVE: The objective of this study was to evaluate the features of flexor
      hallucis longus (FHL), flexor digitorum longus (FDL) and flexor digitorum
      accessorius (FDA) muscles with relevance to the tendon grafts and to reveal the
      location of Master Knot of Henry (MKH). METHODS: Twenty feet from ten formalin
      fixed cadavers were dissected, which were in the inventory of Anatomy Department
      of Medicine Faculty, Mersin University. The location of MKH was identified.
      Interconnections of FHL and FDL were categorized. According to incision
      techniques, lengths of FHL and FDL tendon grafts were measured. Attachment sites
      of FDA were assessed. RESULTS: MKH was 12.61 +/- 1.11 cm proximal to first
      interphalangeal joint, 1.75 +/- 0.39 cm below to navicular tuberosity and 5.93 +/
      0.74 cm distal to medial malleolus. The connections of FHL and FDL were
      classified in 7 types. Tendon graft lengths of FDL according to medial and
      plantar approaches were 6.14 +/- 0.60 cm and 9.37 +/- 0.77 cm, respectively.
      Tendon graft lengths of FHL according to single, double and minimal invasive
      incision techniques were 5.75 +/- 0.63 cm, 7.03 +/- 0.86 cm and 20.22 +/- 1.32
      cm, respectively. FDA was found to be inserting to FHL slips in all cases and it
      inserted to various surfaces of FDL. CONCLUSION: The exact location of MKH and
      slips was determined. Two new connections not recorded in literature were found.
      It was observed that the main attachment site of FDA was the FHL slips. The
      surgical awareness of connections between the FHL, FDL and FDA, which
      participated in the formation of long flexor tendons of toes, could be important
      for reducing possible loss of function after tendon transfers postoperatively.

PMID- 29366541
TI  - A service evaluation and improvement project: a three year systematic audit cycle
      of the physiotherapy treatment for Lateral Epicondylalgia.
AB  - OBJECTIVES: To improve outcomes of physiotherapy treatment for patients with
      Lateral Epicondylalgia. DESIGN: A systematic audit and quality improvement
      project over three phases, each of one year duration. SETTING: Salford Royal NHS
      Foundation Trust Teaching Hospital Musculoskeletal Physiotherapy out-patients
      department. PARTICIPANTS: n=182. INTERVENTIONS: Phase one - individual
      discretion; Phase two - strengthening as a core treatment however individual
      discretion regarding prescription and implementation; Phase three - standardised
      protocol using high load isometric exercise, progressing on to slow combined
      concentric & eccentric strengthening. MAIN OUTCOME MEASURES: Global Rating of
      Change Scale, Pain-free grip strength, Patient Rated Tennis Elbow Evaluation,
      Tampa Scale of Kinesophobia-11. RESULTS: Phase three demonstrated a reduction in
      the average number of treatments by 42% whilst improving the number of responders
      to treatment by 8% compared to phase one. Complete cessation of non-evidence
      based treatments was also observed by phase three. CONCLUSIONS: Strengthening
      should be a core treatment for LE. Load setting needs to be sufficient. In phase
      three of the audit a standardised tendon loading programme using patient specific
      high load isometric exercises into discomfort/pain demonstrated a higher
      percentage of responders compared to previous phases.

PMID- 29366542
TI  - The effects of neurochemical balance in the anterior cingulate cortex and
      dorsolateral prefrontal cortex on volitional control under irrelevant
      distraction.
AB  - Volitional control has been related to the excitatory/inhibitory (E/I) ratio of
      glutamate-glutamine to gamma-aminobutyric acid concentration in the different
      parts of the frontal cortex. Yet, how the neurochemical balance in each of the
      brain areas modulates volitional control remains unclear. Here, participants
      performed an auditory Go/No-Go task with and without task-irrelevant face
      distractors. Neurochemical balance was measured with magnetic resonance
      spectroscopy at rest. Participants with higher E/I ratios in the dorsolateral
      prefrontal cortex (DLPFC) showed less control over No-Go cues under no
      distraction, whereas participants with higher E/I ratios in the anterior
      cingulate cortex (ACC) were more prompted to make speeded Go responses under
      distraction. Therefore, the neurochemical balance in the DLPFC and ACC may be
      involved in the control over task-relevant and -irrelevant cues respectively.

PMID- 29366544
TI  - An (Old) New Strategy to Manage BPSD.

PMID- 29366543
TI  - A meta-analysis of associations between obesity and insomnia diagnosis and
      symptoms.
AB  - Recent research suggests that sleep plays an important role in obesity (OB). No
      systematic reviews have investigated the association between OB and insomnia
      specifically. The present study reviewed the past 10 y of findings on the
      association between insomnia diagnosis (IND) and insomnia symptoms (INS) with OB.
      A total of 67 studies were included in the meta-analyses. Multilevel random
      effects models showed that the odds of having OB among those who had IND was not
      significantly greater than the odds of having OB among those who did not have IND
      (odds ratio (OR) = .80, p = .61). A small, significant cross-sectional
      correlation (r = .06, p = .03) was found between INS and body mass index.
      Longitudinal data were limited. Based on three studies, the odds of developing
      future INS among those who had OB were not significantly greater than those who
      were normal-weight (NW) (OR = 1.07, p = .40). Longitudinal data on the
      association between INS and future incidence of OB are inconclusive. We found no
      indication of systematic publication biases and high heterogeneity in the effect
      sizes across studies. Meta-regressions showed that some of the heterogeneity was
      explained by the types of measures of insomnia symptoms, publication year, and
      regions where a study was conducted.

PMID- 29366545
TI  - Emergence of non-Candida albicans species: Epidemiology, phylogeny and
      fluconazole susceptibility profile.
AB  - OBJECTIVE: Non-Candida albicans (NCA) species now account for a significant part
      of clinical candidiasis worldwide. In the present study, epidemiology and
      antifungal susceptibility profile of NCA isolated from various forms of
      candidiasis were studied with special focus on their phylogenetic relationship by
      ITS sequencing. PATIENTS AND METHODS: Seventy-nine NCA isolates were isolated
      from skin and nail scrapings (67.0%), vaginal discharges (8.8%), blood (8.8%),
      sputa (5.0%), urine (5.0%), oral swabs (2.6%), biopsy and eye tumor, each (1.4%).
      These isolates were identified by morphological, biochemical and molecular (ITS
      sequencing) techniques. In vitro antifungal susceptibility of the isolates to
      fluconazole (FCZ) was tested according to the CLSI method (M27-S4). RESULTS:
      Among a total number of 79 cases of proven NCA infections, C. parapsilosis
      (36.8%) was the most prevalent species followed by C. glabrata (32.9%), C.
      orthopsilosis (11.4%), C. tropicalis (8.9%), C. krusei (5.0%) and C.
      guilliermondii (5.0%). The susceptibility to FCZ was assessed for C. parapsilosis
      (96.5%), C. orthopsilosis (88.9%), C. tropicalis (85.7%) and C. guilliermondii
      (50.0%). C. glabrata and C. krusei isolates were not susceptible to FCZ. NCA
      species were distributed in various phylogenetic clades including C. glabrata
      (1), C. tropicalis (3), C. parapsilosis (6) and C. orthopsilosis, C. krusei and
      C. guilliermondii (each 2). CONCLUSION: C. parapsilosis and C. glabrata were the
      most predominant NCA species involve in the etiology of candidiasis. C.
      orthopsilosis was reported from superficial candidiasis. Taken together, our
      results further substantiate the increasing importance of the involvement of NCA
      species in the etiology of candidiasis.

PMID- 29366546
TI  - The enigmatic role of IL-38 in inflammatory diseases.
AB  - IL-38 is the most recently discovered cytokine of the IL-1 family and is
      considered a potential inhibitor of the IL-1 and Toll-like receptor families. IL
      38 exerts anti-inflammatory properties, especially on macrophages, by inhibiting
      secretion of pro-inflammatory cytokines, leading to reduced T-lymphocyte TH17
      maturation. IL-38 has been studied most extensively in the context of chronic
      inflammatory diseases, particularly arthritis, where it is considered an
      attractive new drug candidate. IL-38 research has entered a new phase, with the
      realization that IL-38 is important in the pathophysiology of TH17 dependent
      diseases (psoriasis, psoriatic arthritis and ankylosing spondylitis). In this
      review, we provide a critical evaluation of several controversial issues
      concerning IL-38 function and regulation. There is effectively contrasting data
      regarding IL-38: it is produced in conditions such as apoptosis, necrosis or
      inflammation, but data is lacking regarding IL-38 processing and biological
      function. Furthermore, the receptor for IL-38 has yet to be identified, although
      three candidate receptors - IL-1R1, IL-36R and IL-1RAPL1-have been proposed.
      Future studies will hopefully uncover new aspects of this enigmatic cytokine.

PMID- 29366547
TI  - HIV Reactivation after Partial Protection by Neutralizing Antibodies.
AB  - It is widely thought that generating broadly neutralizing anti-HIV antibodies
      (BnAbs) will protect humans against HIV, given promising data from in vitro
      experiments and in vivo macaque studies. The primary action of BnAbs is
      preventing cell-free virus from entering cells. Recent in vitro and macaque data
      suggest that BnAbs are less potent against cell-associated virus exposure. We
      speculate that BnAb-based suppression of HIV transmission, particularly if
      mediated by cell-cell transmission, may result in some exposed subjects carrying
      a form of latent (or 'occult') HIV infection. Such largely hidden HIV infections
      may subsequently reactivate when BnAb levels decline. This concept has
      implications for the achievement of long-term sterilizing immunity to HIV.

PMID- 29366548
TI  - Letter to the Editor Regarding "Increased detection of blunt carotid and
      vertebral artery injury after implementation of diagnostic imaging pathway in
      level 1 trauma centre in Western Australia".

PMID- 29366549
TI  - Masquelet technique versus Ilizarov bone transport for reconstruction of lower
      extremity bone defects following posttraumatic osteomyelitis.

PMID- 29366550
TI  - Subtrochanteric fractures of the femur. Treatment with locking intramedullary
      nailing. An experience without C-Arc. The guide-wire stopping method for
      verifying distal locking is described.

PMID- 29366551
TI  - Response to; Letter to the Editor Re: Standardised virtual fracture clinic
      management of radiographically stable Weber B ankle fractures is safe, cost
      effective and reproducible (April 2017).

PMID- 29366552
TI  - Mortality in patients sustaining a periprosthetic fracture following a previous
      extracapsular hip fracture fixation.
AB  - BACKGROUND: Mortality rates following hip fractures are decreasing. As these
      outcomes improve, it increases the potential for further falls and the potential
      to sustain a periprosthetic fracture. The aim of this study was to analyse the 1
      year mortality of periprosthetic fractures around an implant used to treat an
      extracapsular hip fracture. Secondary outcomes included 30 day mortality,
      complications and risk factors associated with mortality. METHODS: A
      retrospective case note and radiographic review of all patients who presented to
      a single institution with a periprosthetic femoral fracture around an implant
      previously used to treat an extracapsular hip fracture between 1st January and
      2008 and 31st May 2015. RESULTS: 29 patients with a mean age of 75.8. 6 males and
      23 females. 20 (69.0%) patients had capacity to consent for surgery. Pre
      operatively 34.5% mobilised independently without any walking aids. 79.3% lived
      at home. 62.1% had a Charlson co-morbidity score of 0 or 1, 27.6% a score of 2 or
      3, 6.9% a score of 4 and 5, and 3.4% a score of more than 5.3.4% was ASA grade 1,
      13.8% ASA2, 65.5% ASA 3 and 17.2% were ASA 4. The previous implant a dynamic hip
      screw in 75.9% dynamic hip screws and an intramedullary nail in 24.1%. There were
      4 (13.8%) in-patient deaths. The 30 day mortality 17.2% (5 patients) was and the
      1 year mortality was 44.8% (13 patients). There were 0 complications that
      required return to surgery during admission. 1 patient with a revision
      intramedullary nail had dynamisation performed due to delayed union 7 months
      following surgery. 1 patient required removal of metalwork 2 years following
      surgery for infection. When comparing risk factors for mortality, there were no
      significant risk factors found in this study for 30 day and 1 year mortality.
      CONCLUSIONS: This paper suggests that periprosthetic fractures sustained after
      the surgical treatment of extra capsular neck of femur fractures have higher
      mortality rates than hip fractures. These patients should be given the same
      priority as these patients in there management.

PMID- 29366553
TI  - The role of computed tomography scans in diaphyseal femur fractures following
      gunshot injuries: A survey of orthopaedic traumatologists.

PMID- 29366554
TI  - The frail fail: Increased mortality and post-operative complications in
      orthopaedic trauma patients: Methodological issues.

PMID- 29366555
TI  - Feasibility of an Image-Based Mobile Health Protocol for Postoperative Wound
      Monitoring.
AB  - BACKGROUND: Surgical site infection (SSI) is the most common nosocomial infection
      and the leading cause of readmission among surgical patients. Many SSIs develop
      in the postdischarge period and are inadequately recognized by patients. To
      address this, we developed a mobile health protocol of remote wound monitoring
      using smartphone technology. The current study aims to establish its feasibility
      among patients and providers. STUDY DESIGN: We enrolled vascular surgery patients
      during their inpatient stay. They were trained to use our mobile health
      application, which allowed them to transmit digital images of their surgical
      wound and answer a survey about their recovery. After hospital discharge,
      participants completed the application daily for 2 weeks. Providers on the
      inpatient team reviewed submissions daily and contacted patients for concerning
      findings. RESULTS: Forty participants were enrolled. Forty-five percent of
      participants submitted data every day for 2 weeks, with an overall submission
      rate of 90.2%. Submissions were reviewed within an average of 9.7 hours of
      submission, with 91.9% of submissions reviewed within 24 hours. We detected 7
      wound complications with 1 false negative. Participant and provider satisfaction
      was universally high. CONCLUSIONS: Patients and their caregivers are willing to
      participate in a mobile health program aimed at remote monitoring of
      postoperative recovery, and they are able to complete it with a high level of
      fidelity and satisfaction. Preliminary results indicate the ability to detect and
      intervene on wound complications.

PMID- 29366556
TI  - Corrigendum to "Distorted leukocyte migration, angiogenesis, wound repair and
      metastasis in Tspan8 and Tspan8/CD151 double knockout mice indicate complementary
      activities of Tspan8 and CD51" [Biochim. Biophys. Acta 1865(2) (2018) 379-391].

PMID- 29366557
TI  - [Tacit Knowledge: Characteristics in nursing practice].
AB  - INTRODUCTION: Tacit knowledge can be defined as knowledge which is used
      intuitively and unconsciously, which is acquired through one's experience,
      characterized by being personal and contextual. Some terms such as 'intuition',
      'know how' and 'implicit knowledge' have been used to describe tacit knowledge.
      Different disciplines in the fields of management or health have studied tacit
      knowledge, identifying it as a powerful tool to create knowledge and clinical
      decision-making. The aim of this review is to analyse the definition and
      characteristics that make up tacit knowledge and determine the role it plays in
      the nursing discipline. METHODS: An integrative review was undertaken of the
      literature published up to November 2016 in the databases CUIDEN, SciELO, PubMed,
      Cochrane and CINAHL. The synthesis and interpretation of the data was performed
      by two researchers through content analysis. RESULTS: From a total of 819
      articles located, 35 articles on tacit knowledge and nursing were chosen. There
      is no consensus on the name and description of results in tacit knowledge. The
      main characteristics of tacit knowledge have a personal and social character,
      which is used from an organised mental structure, called mindline. This structure
      relates to the use of tacit knowledge on clinical decision-making. CONCLUSIONS:
      Previous studies on tacit knowledge and nursing provide the nursing community
      with perspectives without going into depth. The production of a framework is
      suggested, as it would clarify implied concepts and its role on the management of
      nursing knowledge.

PMID- 29366558
TI  - Monitoring emerging contaminants in the drinking water of Milan and assessment of
      the human risk.
AB  - Emerging Contaminants (ECs) are ubiquitous in waters, arousing concern because of
      their potential risks for human health and the environment. This study
      investigated the presence of multiple classes of ECs in 21 wells over the
      drinking water network of Milan, in the most inhabited and industrialized area of
      Italy, and assessed the risks for consumers. Samples were analyzed using liquid
      chromatography coupled to mass spectrometry. Human risk assessment (HRA) was
      conducted by comparing the measured concentrations with drinking water thresholds
      from guidelines or calculated in this study; first considering the exposure to
      each single EC and then the entire mixture. Thirteen ECs were measured in the low
      ng/L range, and were generally detected in less than half of the wells.
      Pharmaceuticals, perfluorinated substances, personal care products, and
      anthropogenic markers were the most frequently detected. The results of the HRA
      excluded any risks for consumers in each scenario considered. This is one of the
      most comprehensive studies assessing the presence of a large number of ECs in the
      whole drinking water network of a city, and the risks for human health. Results
      improve the limited information on ECs sources and occurrence in drinking water
      and help establishing guidelines for regulatory purposes.

PMID- 29366560
TI  - Lumbar loads and trunk kinematics in people with a transtibial amputation during
      sit-to-stand.
AB  - People with a transtibial amputation have numerous secondary health conditions,
      including an increased prevalence of low back pain. This increased prevalence may
      be partially explained by altered low back biomechanics during movement. The
      purpose of this study was to compare trunk kinematics and L4-L5 lumbar loads in
      people with and without a transtibial amputation during sit-to-stand. Motion
      capture, ground reaction force and electromyographic data were collected from
      eight people with a unilateral transtibial amputation and eight people without an
      amputation during five self-paced sit-to-stand motions. A musculoskeletal model
      of the torso, lumbar spine, pelvis, lower limbs, and 294 muscles was used in a
      static optimization framework to quantify L4-L5 loads, low back muscle forces,
      and trunk kinematics. Participants with an amputation had greater peak and
      average L4-L5 loading in compression compared to control participants, with peak
      loading occurring shortly after liftoff from the chair. At the instant of peak
      loading, participants with an amputation had significantly greater segmental
      trunk lateral bending and trunk-pelvis axial rotation toward the intact side, and
      significantly greater segmental trunk axial rotation toward the prosthetic side
      compared to control participants. Participants with an amputation also had
      greater peak frontal plane and transverse plane segmental trunk angular velocity.
      The postural differences observed in people with a transtibial amputation were
      consistent with their ground reaction force asymmetry. The cumulative effects of
      the altered movement strategy used by people with an amputation may result in an
      increased risk for low back pain development over time.

PMID- 29366559
TI  - Hip chondrolabral mechanics during activities of daily living: Role of the labrum
      and interstitial fluid pressurization.
AB  - Osteoarthritis of the hip can result from mechanical factors, which can be
      studied using finite element (FE) analysis. FE studies of the hip often assume
      there is no significant loss of fluid pressurization in the articular cartilage
      during simulated activities and approximate the material as incompressible and
      elastic. This study examined the conditions under which interstitial fluid load
      support remains sustained during physiological motions, as well as the role of
      the labrum in maintaining fluid load support and the effect of its presence on
      the solid phase of the surrounding cartilage. We found that dynamic motions of
      gait and squatting maintained consistent fluid load support between cycles, while
      static single-leg stance experienced slight fluid depressurization with
      significant reduction of solid phase stress and strain. Presence of the labrum
      did not significantly influence fluid load support within the articular
      cartilage, but prevented deformation at the cartilage edge, leading to lower
      stress and strain conditions in the cartilage. A morphologically accurate
      representation of collagen fibril orientation through the thickness of the
      articular cartilage was not necessary to predict fluid load support. However,
      comparison with simplified fibril reinforcement underscored the physiological
      importance. The results of this study demonstrate that an elastic incompressible
      material approximation is reasonable for modeling a limited number of cyclic
      motions of gait and squatting without significant loss of accuracy, but is not
      appropriate for static motions or numerous repeated motions. Additionally,
      effects seen from removal of the labrum motivate evaluation of labral
      reattachment strategies in the context of labral repair.

PMID- 29366561
TI  - Analysis of hierarchical biomechanical data structures using mixed-effects
      models.
AB  - Rigorous statistical analysis of biomechanical data is required to understand
      tissue properties. In biomechanics, samples are often obtained from multiple
      biopsies in the same individual, multiple samples tested per biopsy, and multiple
      tests performed per sample. The easiest way to analyze this hierarchical design
      is to simply calculate the grand mean of all samples tested. However, this may
      lead to incorrect inferences. In this report, three different analytical
      approaches are described with respect to the analysis of hierarchical data
      obtained from muscle biopsies. Each method was used to analyze an actual
      experimental data set obtained from muscle biopsies of three different muscles in
      the human forearm. The results illustrate the conditions under which mixed-models
      or simple models are acceptable for analysis of these types of data.

PMID- 29366562
TI  - Recent advances in the understanding of microglial development and homeostasis.
AB  - Microglia are the resident macrophages of the central nervous system (CNS). These
      pivotal cells arise early during embryonic development and provide both
      developmental support and immune protection to the brain. In adults, microglia
      contribute to brain homeostasis and mediate an intriguing interplay between the
      CNS and the gut microbiota. When dysregulated, microglia are also implicated in
      numerous neurological disorders, and thus fully understanding their regulation
      and functions will facilitate rational design of therapies to alleviate these
      conditions; however it remains unclear how the multiple factors modulating
      microglial activity are integrated at the organism and cellular levels. In this
      review, we will discuss recent advances in the understanding of microglial
      regulation and highlight the key questions that remain to be answered around
      microglial development, homeostasis and functions.

PMID- 29366563
TI  - Pneumococcal DNA-binding proteins released through autolysis induce the
      production of proinflammatory cytokines via toll-like receptor 4.
AB  - Streptococcus pneumoniae is a leading cause of bacterial pneumonia. Our previous
      study suggested that S. pneumoniae autolysis-dependently releases intracellular
      pneumolysin, which subsequently leads to lung injury. In this study, we
      hypothesized that pneumococcal autolysis induces the leakage of additional
      intracellular molecules that could increase the pathogenicity of S. pneumoniae.
      Liquid chromatography tandem-mass spectrometry analysis identified that chaperone
      protein DnaK, elongation factor Tu (EF-Tu), and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) were released with pneumococcal DNA by autolysis. We
      demonstrated that recombinant (r) DnaK, rEF-Tu, and rGAPDH induced significantly
      higher levels of interleukin-6 and tumor necrosis factor production in peritoneal
      macrophages and THP-1-derived macrophage-like cells via toll-like receptor 4.
      Furthermore, the DNA-binding activity of these proteins was confirmed by surface
      plasmon resonance assay. We demonstrated that pneumococcal DnaK, EF-Tu, and GAPDH
      induced the production of proinflammatory cytokines in macrophages, and might
      cause host tissue damage and affect the development of pneumococcal diseases.

PMID- 29366564
TI  - Characterizing Disease Burden and Progression of Geographic Atrophy Secondary to
      Age-Related Macular Degeneration.
AB  - PURPOSE: To understand levels of disease burden and progression in a real-world
      setting among patients from the United Kingdom with bilateral geographic atrophy
      (GA) secondary to age-related macular degeneration (AMD). DESIGN: Retrospective
      cohort analysis of a multicenter electronic medical record (EMR) database.
      PARTICIPANTS: Patients who were aged >=50 years with bilateral GA and no history
      of choroidal neovascularization (CNV) and who attended 1 of 10 clinical sites
      using the EMR. METHODS: A deidentified data set was constructed from the records
      held at the 10 sites. An algorithm was used to extract cases with a GA diagnosis,
      of which 1901 had bilateral GA and form the basis of this report. A sample of
      records randomly selected from each center was used to validate disease
      definitions. MAIN OUTCOME MEASURES: Progression to blindness (visual acuity [VA]
      <20 letters or Snellen 3/60 in the better-seeing eye), driving ineligibility (VA
      <=70 letters or Snellen 6/12 in the better-seeing eye), progression to CNV, loss
      of 10 or more letters, and mean change in VA over time. RESULTS: At first record
      of GA, 7.1% had a VA in the better-seeing eye equal to or lower than the cutoff
      for blindness registration and 71.1% had a VA that would have rendered them
      ineligible to drive. Over time, 16% became legally blind (median time to outcome,
      6.2 years) and 66.7% became ineligible to drive (median time to outcome, 1.6
      years). In the worse-seeing eye, 40.1% lost >=10 letters in 2.4 years. Among
      patients with baseline and 24-month VA measurements, mean VA decline was 6.1
      letters in the worse-seeing eye (n = 413) and 12.4 letters in the better-seeing
      eye (n = 414). The rate of progression to CNV in either eye was 7.4% per patient
      year. CONCLUSIONS: At initial diagnosis, based on VA in the better-seeing eye, a
      high proportion of patients with bilateral GA were ineligible to drive and
      approximately 7% were eligible for UK blindness registration. The subsequent
      reduction in VA that occurred in the better-seeing eye would render a further two
      thirds ineligible to drive. These findings emphasize the severity of the visual
      disability associated with GA secondary to AMD.

PMID- 29366565
TI  - IL-31: A new key player in dermatology and beyond.
AB  - IL-31 is a novel cytokine expressed in many human tissues and involved mainly in
      TH2-weighted inflammation. IL-31 signals through a receptor complex consisting of
      IL-31 receptor alpha and oncostatin M receptor beta. The available data show that
      IL-31 is strongly linked with chronic pruritic skin disorders, such as atopic
      eczema, and represents a novel target for directed drug therapy. Regulation of
      immune responses and cellular differentiation and proliferation are recently
      elucidated effects of IL-31, suggesting a more complex and diverse area of effect
      for this novel cytokine. This review summarizes the current knowledge on IL-31
      and its receptors and the involvement of IL-31 in diseases both in human subjects
      and mouse models.

PMID- 29366566
TI  - Inadequate preoperative nutrition might be associated with acute kidney injury
      and greater illness severity postoperatively.
AB  - OBJECTIVE: Nutrition is vital for maintaining optimal cellular and organ
      function, particularly in neonates who undergo cardiac surgery. Achieving
      nutritional goals preoperatively can be challenging because of fluid
      restrictions, suboptimal oral intake, and concerns for inadequate
      gastrointestinal circulation. We examined preoperative caloric intake and its
      effects on postoperative course in neonates who underwent cardiac surgery.
      METHODS: We retrospectively reviewed records of neonates (younger than 30 days)
      who underwent congenital heart surgery requiring cardiopulmonary bypass from 2008
      to 2014 at Arnold Palmer Hospital for Children. Data on multiple nutritional and
      postoperative variables were collected. Study outcomes included hospital length
      of stay, duration of mechanical ventilation, and acute kidney injury (AKI).
      RESULTS: Records of 95 neonates were reviewed. Sixty-six patients (69.5%) with a
      median age of 5 days did not achieve preoperative caloric goal, whereas 29
      patients (30.5%) with a median age of 11 days did. Of those who achieved caloric
      goal, 6 (20.6%) achieved it via total parental nutrition, 9 (31.1%) with a
      combination of total parental nutrition and enteral feeds, and 14 (48.3%) via
      enteral route. There was a significant difference in peak lactate (P = .002),
      inotropic score (P = .02), and duration of mechanical ventilation (P = .013)
      between those who did and did not achieve caloric goal. In multivariable analysis
      we found that failure to achieve caloric goal preoperatively was independently
      associated with stage 2 or 3 AKI (P = .04; odds ratio, 4.48; 95% confidence
      interval, 1.02-19.63) and younger age at the time of surgery (P < .001; odds
      ratio, 0.12; 95% confidence interval, 0.04-0.33). CONCLUSIONS: Failure to achieve
      preoperative caloric goal might contribute to development of AKI and might be
      associated with greater severity of illness postoperatively.

PMID- 29366567
TI  - Evaluating the best approach to treatment of aortic stenosis: The jury is still
      out.

PMID- 29366568
TI  - Discussion.

PMID- 29366569
TI  - The Fontan circulation: Time for a moon shot?

PMID- 29366570
TI  - Off-pump versus on-pump coronary artery bypass grafting: Insights from the
      Arterial Revascularization Trial.
AB  - BACKGROUND: The long-term effects of off-pump coronary artery bypass continue to
      be controversial because some studies have reported increased adverse event rates
      with off-pump coronary artery bypass when compared with on-pump coronary artery
      bypass. The Arterial Revascularization Trial compared survival after bilateral
      versus single internal thoracic artery grafting. The choice of off-pump coronary
      artery bypass versus on-pump coronary artery bypass was based on the surgeon's
      discretion. We performed a post hoc analysis of the Arterial Revascularization
      Trial to compare 5-year outcomes with 2 strategies. METHODS: Among 3102 patients
      enrolled in the Arterial Revascularization Trial, we selected 1260 patients who
      underwent off-pump coronary artery bypass versus 1700 patients who underwent on
      pump coronary artery bypass with cardioplegic arrest for the present comparison.
      Primary outcomes were 5-year mortality and incidence of major cardiac and
      cerebrovascular events, including cardiovascular death, myocardial infarction,
      cerebrovascular accident, and revascularization after index procedure. Propensity
      score matching selected 1260 pairs for final comparison. Stratified Cox models
      were used for treatment effect estimate. RESULTS: Hospital mortality was
      comparable between off-pump coronary artery bypass and on-pump coronary artery
      bypass groups (12 [1.0%] vs 15 [1.2%]; P = .7). Conversion rate to on-pump during
      off-pump coronary artery bypass was 29 of 1260 (2.3%). When compared with off
      pump coronary artery bypass not converted, off-pump coronary artery bypass
      converted to on-pump presented a remarkably higher hospital mortality (10.3% vs
      0.7%; P < .001). At 5 years, the mortality rate was 110 (8.9%) versus 102 (8.3%)
      in the off-pump coronary artery bypass and on-pump coronary artery bypass groups,
      respectively, with no significant difference (hazard ratio, 1.14; 95% confidence
      interval, 0.86-1.52; P = .35). Incidence of major cardiac and cerebrovascular
      events was 175 (14.3) versus 169 (13.8) in the off-pump coronary artery bypass
      and on-pump coronary artery bypass groups, respectively, with no significant
      difference (hazard ratio, 1.05; 95% confidence interval, 0.84-1.31; P = .65).
      CONCLUSIONS: The present post hoc Arterial Revascularization Trial analysis
      supports the hypothesis that both off-pump coronary artery bypass and on-pump
      coronary artery bypass are equally effective and safe.

PMID- 29366571
TI  - Landing in zone 0: Is ascending thoracic endovascular aortic repair ready for
      takeoff?

PMID- 29366572
TI  - Leukemoid reaction: Case report.

PMID- 29366573
TI  - Aortic dissection: A little help from our friends.

PMID- 29366574
TI  - Prediction models for disease events do not always influence clinical practice.

PMID- 29366575
TI  - The large database analysis: A useful "Band-Aid" solution.

PMID- 29366576
TI  - Redefinition of tricuspid valve structures for successful ring annuloplasty.
AB  - BACKGROUND: Although numerous reports have described suturing techniques for
      tricuspid annuloplasty, most studies were not based on a detailed anatomy of the
      tricuspid annulus. Thus, the definition of the tricuspid commissures remains
      unclear. This study aimed to clearly define the commissures and leaflets of the
      tricuspid valve and subvalvular structures, and to define a standard method for
      tricuspid annuloplasty. METHODS: In 27 normal heart specimens without cardiac
      disease, the tricuspid commissure was defined using indentations of the leaflets
      as a point, not an area, and the length of each tricuspid annulus was measured.
      The relationships between the leaflets and the subvalvular structures were then
      examined. RESULTS: In most specimens, the posterior leaflet had 2 (62.9%) or 3
      (29.6%) scallops, providing further evidence of posterior leaflet diversity. In
      addition, the posterior leaflet had 1 or 2 indentations, which can be mistaken
      for true commissures. The annulus of the posterior leaflet was significantly
      longer than the annuli of the other 2 leaflets (P < .00428). The annuli of the
      septal and the anterior leaflets were supported by the interventricular septum
      and the supraventricular crest, respectively, whereas the posterior leaflet
      annulus was distributed largely along the right ventricular free wall.
      CONCLUSIONS: There was a structural gap between the tricuspid leaflet
      indentations and the subvalvular structures. The relationships among the
      leaflets, commissures, and subvalvular structures differed in the septal,
      anterior, and posterior leaflets. This new definition of the commissural point
      may aid the development of a clear-cut methodology for prosthetic ring
      annuloplasty.

PMID- 29366577
TI  - A comparison between Belsey Mark IV and laparoscopic Nissen fundoplication in
      patients with large paraesophageal hernia.
AB  - OBJECTIVES: Laparoscopic Nissen fundoplication is the most commonly performed
      operation for the repair of large hiatal hernias. We compared outcomes between
      the Belsey Mark IV fundoplication and the laparoscopic Nissen fundoplication.
      METHODS: A retrospective review was performed over a 10-year period on patients
      who had repair of large paraesophageal hernia. Patients who received the Belsey
      Mark IV (n = 118) were matched 1 to 1, by year of surgery, gender, and age, with
      patients who received laparoscopic Nissen fundoplication. We compared these 2
      groups, examining recurrence, need for reoperation, perioperative outcomes, and
      symptomatic follow-up as defined by the Gastroesophageal Reflux Disease-Health
      Related Quality of Life questionnaire. RESULTS: Recurrence rates were similar
      between patients who had a Belsey Mark IV and laparoscopic Nissen fundoplication
      (8.4% vs 16.1%, P = .11). However, the esophageal leak rate was higher in
      patients who received a laparoscopic Nissen fundoplication compared with the
      Belsey Mark IV (6.8% vs 0%, respectively, P = .006), and patients who received a
      laparoscopic Nissen fundoplication had higher rates of reoperation (9.3% vs 2.5%,
      respectively, P = .05). Gastroesophageal Reflux Disease-Health Related Quality of
      Life symptom scores were similar between groups with symptoms in laparoscopic
      Nissen fundoplication and Belsey Mark IV, being excellent (74.4% vs 81.4%), good
      (9.3% vs 7.0%), fair (9.3% vs 0), and poor (7.0% vs 11.6%), respectively (P =
      .52). CONCLUSIONS: Laparoscopic Nissen fundoplication for large paraesophageal
      hernias was associated with an increased incidence of leak and reoperation when
      compared with Belsey fundoplication. Belsey Mark IV fundoplication should be
      considered when deciding on what operation to perform in patients with large
      paraesophageal hernias.

PMID- 29366578
TI  - Arterial cannulation site selection: The road less traveled.

PMID- 29366579
TI  - Extracorporeal membrane oxygenation for everyone?

PMID- 29366580
TI  - Urinary biomarkers may provide prognostic information for subclinical acute
      kidney injury after cardiac surgery.
AB  - OBJECTIVE: This study aimed to determine the biomarker-specific outcome patterns
      and short-and long-term prognosis of cardiac surgery-asoociated acute kidney
      injury (AKI) identified by standard criteria and/or urinary kidney biomarkers.
      METHODS: Patients enrolled (N = 200), originated a German multicenter study
      (NCT00672334). Standard risk injury, failure, loss, and end-stage renal disease
      classification (RIFLE) criteria (including serum creatinine and urine output) and
      urinary kidney biomarker test result (neutrophil gelatinase-associated lipocalin,
      midkine, interleukin 6, and proteinuria) were used for diagnosis of postoperative
      AKI. Primary end point was acute renal replacement therapy or in-hospital
      mortality. Long-term end points among others included 5-year mortality. Patients
      with single-biomarker-positive subclinical AKI (RIFLE negative) were identified.
      We controlled for systemic inflammation using C-reactive protein test. RESULTS:
      Urinary biomarkers (neutrophil gelatinase-associated lipocalin, midkine, and
      interleukin 6) were identified as independent predictors of the primary end
      point. Neutrophil gelatinase-associated lipocalin, midkine, or interleukin 6
      positivity or de novo/worsening proteinuria identified 21.1%, 16.9%, 30.5%, and
      48.0% more cases, respectively, with likely subclinical AKI (biomarker
      positive/RIFLE negative) additionally to cases with RIFLE positivity alone.
      Patients with likely subclinical AKI (neutrophil gelatinase-associated lipocalin
      or interleukin 6 positive) had increased risk of primary end point (adjusted
      hazard ratio, 7.18; 95% confidence interval, 1.52-33.93 [P = .013] and hazard
      ratio, 6.27; 95% confidence interval, 1.12-35.21 [P = .037]), respectively.
      Compared with biomarker-negative/RIFLE-positive patients, neutrophil gelatinase
      associated lipocalin positive/RIFLE-positive or midkine-positive/RIFLE-positive
      patients had increased risk of primary end point (odds ratio, 9.6; 95% confidence
      interval, 1.4-67.3 [P = .033] and odds ratio, 14.7; 95% confidence interval, 2.0
      109.2 [P = .011], respectively). Three percent to 11% of patients appear to be
      influenced by single-biomarker-positive subclinical AKI. During follow-up, kidney
      biomarker-defined short-term outcomes appeared to translate into long-term
      outcomes. CONCLUSIONS: Urinary kidney biomarkers identified RIFLE-negative
      patients with high-risk subclinical AKI as well as a higher risk subgroup of
      patients among RIFLE-AKI-positive patients. These findings support the concept
      that urinary biomarkers define subclinical AKI and higher risk subpopulations
      with worse long-term prognosis among standard patients with AKI.

PMID- 29366581
TI  - Rwanda is rising.

PMID- 29366582
TI  - A novel restorative pulmonary valved conduit in a chronic sheep model: Mid-term
      hemodynamic function and histologic assessment.
AB  - OBJECTIVE: To evaluate the safety and the short-term function of a novel
      pulmonary valved conduit (Xeltis Pulmonary Valved Conduit; XPV) up to 12 months
      in a sheep model. METHODS: XPV and Hancock bioprosthetic valved conduits (H, used
      as control) were implanted in adult sheep in the pulmonary artery position.
      Animals were killed at 2 months (n = 6 XPV), 6 months (n = 6 XPV and n = 3 H),
      and 12 months (n = 6 XPV) and examined histologically. During follow-up, function
      of the device as well as diameter of both XPV and H were assessed by
      transthoracic echocardiography. RESULTS: Of 18 animals that received an XPV, 15
      survived until they were killed; 3 animals that received H survived the planned
      observational interval. XPV showed mild neointimal thickening and degradation
      beginning at 2 months with an ongoing process until 12 months. Only 1 of the 18
      animals with XPV had significant calcification at 6 months. Pathologic specimen
      did not show any significant narrowing of the conduit whereas neointimal
      thickness showed a peak at 6 months. Inflammatory process reached a maximum at 6
      months and the degradation process at 12 months. Gel permeation chromatography
      analysis showed molecular weight loss beginning at 2 months with a peak at 12
      months for the conduit with slower absorption for the leaflets. The wall of the H
      conduits showed more neointimal thickening, narrowing, and calcification compared
      with XPV, but the leaflets demonstrated minimal changes. CONCLUSIONS: Both
      conduits demonstrated an acceptable safety and functionality. Significant
      calcification was rarely observed in the XPV, whereas the H developed more
      neointimal thickness with calcification of the porcine aortic root portion of the
      wall.

PMID- 29366583
TI  - Transcatheter aortic valve replacement, The Journal of Thoracic and
      Cardiovascular Surgery, and the evolution of clinical research in cardiothoracic
      surgery.

PMID- 29366585
TI  - Corrigendum to "Phosphorylated-tyrosine based pseudobioaffinity adsorbent for the
      purification of immunoglobulin G" [J. Chromatogr. B, 1052 (2017) 10-18].

PMID- 29366584
TI  - Corrigendum to "Premature ovarian senescence and a high miscarriage rate impair
      fertility in women with HCV" [J Hepatol 68 (2018) 33-41].

PMID- 29366586
TI  - Computer-Assisted Decision Support System in Pulmonary Cancer detection and stage
      classification on CT images.
AB  - Pulmonary cancer is considered as one of the major causes of death worldwide. For
      the detection of lung cancer, computer-assisted diagnosis (CADx) systems have
      been designed. Internet-of-Things (IoT) has enabled ubiquitous internet access to
      biomedical datasets and techniques; in result, the progress in CADx is
      significant. Unlike the conventional CADx, deep learning techniques have the
      basic advantage of an automatic exploitation feature as they have the ability to
      learn mid and high level image representations. We proposed a Computer-Assisted
      Decision Support System in Pulmonary Cancer by using the novel deep learning
      based model and metastasis information obtained from MBAN (Medical Body Area
      Network). The proposed model, DFCNet, is based on the deep fully convolutional
      neural network (FCNN) which is used for classification of each detected pulmonary
      nodule into four lung cancer stages. The performance of proposed work is
      evaluated on different datasets with varying scan conditions. Comparison of
      proposed classifier is done with the existing CNN techniques. Overall accuracy of
      CNN and DFCNet was 77.6% and 84.58%, respectively. Experimental results
      illustrate the effectiveness of proposed method for the detection and
      classification of lung cancer nodules. These results demonstrate the potential
      for the proposed technique in helping the radiologists in improving nodule
      detection accuracy with efficiency.

PMID- 29366587
TI  - Ocular manifestations of Zika virus: What we should know and what we should do.

PMID- 29366588
TI  - Comparison of objective optical quality measured by double-pass aberrometry in
      patients with moderate dry eye: Normal saline vs. artificial tears: A pilot
      study.
AB  - Dry eye is defined by a tear film instability resulting in variable but
      systematic fluctuations in quality of vision. Variability in optical quality can
      be demonstrated using a double pass aberrometer such as the Optical Quality
      Analyzing System, Visiometrics (OQAS). The goal of this work is to compare
      fluctuations in objective quality of vision measured by OQAS between treatment
      with normal saline eye drops and treatment with carmellose 0.5% and hyaluronic
      acid 0.1% (Optive Fusion [OF], Allergan) in patients with moderate dry eye
      syndrome. Optical quality was measured by evaluating the variations in the
      Optical Scattering Index (OSI) over 20seconds using the OQAS. Inclusion criteria
      were dry eye syndrome with an ocular surface disease index (OSDI) score >23
      treated only with artificial tears. The patients were their own controls: OF in
      one eye and normal saline in the fellow eye. The choice of the subject eye and
      control eye was determined in a randomized fashion. OSI variations were measured
      in each eye before instillation, 5minutes and 2hours after instillation. The
      primary endpoint was OSI fluctuation over 20seconds of measurement. Secondary
      endpoints were the number of blinks and patient preference (preferred eye).
      Preliminary results were obtained on 19 patients. Average OSDI score was 36.8.
      Visual acuity was 10/10 with no significant difference between the two eyes.
      Prior to instillation, there was no significant difference between "normal
      saline" and "OF" eyes in terms of OSI, OSI variability or number of blinks. In
      the normal saline eye, there were no significant variations in mean OSI, OSI
      variability, OSI slope, or number of blinks. However, in the "OF" eye, there was
      a significant variation between initial and 2-hour OSI variability (0.363 versus
      0.204, P<0.05), the average slope of OSI (0.04 versus 0.01, P<0.05) and the
      number of blinks (4.2 versus 2.8, P<0.05). Among the patients, 65% preferred the
      OF eye, 24% did not have a preference, and 11% preferred the normal saline eye.
      Objective quality of vision measured by OQAS is an interesting parameter for
      evaluating the effectiveness of a lacrimal substitute. The purpose of artificial
      tears is, among other things, to provide comfort and a reduction of dry eye
      symptoms such as poor quality of vision. This study demonstrates that 0.5%
      carmellose and 0.1% hyaluronic acid allowed better stabilization of the tear film
      and thus a significant improvement in the quality of vision compared to normal
      saline.

PMID- 29366589
TI  - [Atypical traumatic hyphema].

PMID- 29366590
TI  - [An iatrogenic posterior subcapsular cataract].

PMID- 29366591
TI  - [Endogenous endophthalmitis as a complication of varicose ulcer of the leg: Case
      report].

PMID- 29366592
TI  - [Atypical clinical presentation of an orbital cylindroma].

PMID- 29366593
TI  - Role of the chemokine receptors CXCR3, CXCR4 and CCR7 in the intramuscular
      recruitment of plasmacytoid dendritic cells in dermatomyositis.
AB  - To explore the possible mechanism implicated in the recruitment of plasmacytoid
      dendritic cells (pDCs), we investigated the expression of the chemokine receptors
      CXCR3, CXCR4, and CCR7 on intramuscular and circulating pDCs from patients with
      dermatomyositis (DM). Using immunohistochemistry, preferential expression of
      CXCR3, CXCR4 and CCR7 was identified in the perivascular inflammatory infiltrates
      within the perimysium in DM muscle. Western-blot analysis showed marked up
      regulation of expression of CXCR3, CXCR4 and CCR7 in muscle homogenate from
      patients with DM compared with that in non-diseased controls. Co-localization of
      CD303+ pDCs with these chemokine receptors was further examined by double
      immunofluorescence staining, which showed extensive co-localization of CD303 with
      CXCR3/CXCR4/CCR7 in DM biopsies. Flow cytometry was then used to investigate the
      proportion of pDCs among the total PBMCs and the expression of CXCR3, CXCR4 and
      CCR7 on circulating pDCs. The proportion of CD123+CD303+ pDCs in peripheral blood
      from DM patients was markedly decreased compared to that from polymyositis (PM)
      patients and normal controls. Significantly increased expression of CXCR3, but
      not CXCR4 or CCR7, was further identified on circulating pDCs in DM. Correlation
      analysis showed that the expression of CXCR3 correlated inversely with the
      frequency of pDCs in peripheral blood. Our findings indicate that the chemokine
      receptors, CXCR3, CXCR4 and CCR7 may be involved in the recruitment of pDCs from
      peripheral blood to muscle tissues in DM via different mechanisms, and in which
      CXCR3 may play an important role under DM conditions.

PMID- 29366596
TI  - The potential use of social media and other internet-related data and
      communications for child maltreatment surveillance and epidemiological research:
      Scoping review and recommendations.
AB  - Collecting child maltreatment data is a complicated undertaking for many reasons.
      As a result, there is an interest by child maltreatment researchers to develop
      methodologies that allow for the triangulation of data sources. To better
      understand how social media and internet-based technologies could contribute to
      these approaches, we conducted a scoping review to provide an overview of social
      media and internet-based methodologies for health research, to report results of
      evaluation and validation research on these methods, and to highlight studies
      with potential relevance to child maltreatment research and surveillance. Many
      approaches were identified in the broad health literature; however, there has
      been limited application of these approaches to child maltreatment. The most
      common use was recruiting participants or engaging existing participants using
      online methods. From the broad health literature, social media and internet-based
      approaches to surveillance and epidemiologic research appear promising. Many of
      the approaches are relatively low cost and easy to implement without extensive
      infrastructure, but there are also a range of limitations for each method.
      Several methods have a mixed record of validation and sources of error in
      estimation are not yet understood or predictable. In addition to the problems
      relevant to other health outcomes, child maltreatment researchers face additional
      challenges, including the complex ethical issues associated with both internet
      based and child maltreatment research. If these issues are adequately addressed,
      social media and internet-based technologies may be a promising approach to
      reducing some of the limitations in existing child maltreatment data.

PMID- 29366595
TI  - Risk factors for arterial hypertension after liver transplantation.
AB  - Arterial hypertension represents a common complication of immunosuppressive
      therapy after liver transplantation (LT). The aim of the study is to evaluate the
      prevalence and risk factors associated with hypertension after LT. From a cohort
      of 323 cirrhotic patients who underwent LT from 2008 to 2012, 270 patients were
      retrospectively evaluated, whereas 53 (16.4%) patients deceased. Hypertension was
      defined as blood pressure >=140/90 mm Hg in at least two visits and/or the need
      for antihypertensive therapy. The prevalence of hypertension was 15% before LT
      and significantly increased up to 53% after LT (P < .001). Mean follow-up was 43
      +/- 19 months. In normotensive (NT) subjects at baseline, 35.9% developed
      sustained hypertension after LT, whereas 15.2% developed transient hypertension
      within the first month after LT, and then returned NT. The development of
      sustained hypertension after LT was related to the mammalian target of rapamycin
      inhibitor treatment (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.26
      13.48; P = .02), alcoholic cirrhosis before LT (OR, 3.38; 95% CI, 1.44-8.09; P =
      .005), and new-onset hepatic steatosis after LT (OR, 2.13; 95% CI, 1.10-4.11; P =
      .02). Tacrolimus, the etiology and severity of liver disease, and other
      immunosuppressive regimens were not related to the development of hypertension
      after LT. In our cohort, the prevalence of arterial hypertension has increased up
      to 53% after LT, and metabolic comorbidities and immunosuppressive treatment with
      mammalian target of rapamycin inhibitors are the risk factors for the development
      of hypertension after LT.

PMID- 29366597
TI  - Conducting evaluation research with children exposed to violence: How
      technological innovations in methodologies and data collection may enhance the
      process.
AB  - Research and program evaluation processes that engage children and youth are
      becoming much more common due to influences from children's rights and the
      acknowledgement that children have the capacity to contribute to research, both
      as participants and co-researchers (Roberts, 2017). Recent technological advances
      in the form of tablet and internet-based applications have provided researchers
      with additional methodological tools to better capture the voices and experiences
      of children and their caregivers (Livingstone & Blum-Ross, 2017). However, little
      has been written on the ways in which these new technological advances can
      improve research experiences for children who have been exposed to intimate
      partner and family violence, as well as other forms of traumatic experiences.
      This paper provides a review of current literature and a case study example of
      how one children's mental health agency has implemented tablet-based data
      collection procedures.

PMID- 29366594
TI  - The neonatal anti-viral response fails to control measles virus spread in neurons
      despite interferon-gamma expression and a Th1-like cytokine profile.
AB  - Neonates are highly susceptible to viral infections in the periphery, potentially
      due to deviant cytokine responses. Here, we investigated the role of interferon
      gamma (IFNgamma), a key anti-viral in the neonatal brain. We found that (i)
      IFNgamma, which is critical for viral control and survival in adults, delays
      mortality in neonates, (ii) IFNgamma limits infiltration of macrophages,
      neutrophils, and T cells in the neonatal brain, (iii) neonates and adults
      differentially express pathogen recognition receptors and Type I interferons in
      response to the infection, (iv) both neonates and adults express IFNgamma and
      other Th1-related factors, but expression of many cytokines/chemokines and
      IFNgamma-responsive genes is age-dependent, and (v) administration of IFNgamma
      extends survival and reduces CD4 T cell infiltration in the neonatal brain. Our
      findings suggest age-dependent expression of cytokine/chemokine profiles in the
      brain and distinct dynamic interplays between lymphocyte populations and
      cytokines/chemokines in MV-infected neonates.

PMID- 29366598
TI  - Translational Radiomics: Defining the Strategy Pipeline and Considerations for
      Application-Part 2: From Clinical Implementation to Enterprise.
AB  - Enterprise imaging has channeled various technological innovations to the field
      of clinical radiology, ranging from advanced imaging equipment and
      postacquisition iterative reconstruction tools to image analysis and computer
      aided detection tools. More recently, the advancement in the field of
      quantitative image analysis coupled with machine learning-based data analytics,
      classification, and integration has ushered in the era of radiomics, a paradigm
      shift that holds tremendous potential in clinical decision support as well as
      drug discovery. However, there are important issues to consider to incorporate
      radiomics into a clinically applicable system and a commercially viable solution.
      In this two-part series, we offer insights into the development of the
      translational pipeline for radiomics from methodology to clinical implementation
      (Part 1) and from that point to enterprise development (Part 2). In Part 2 of
      this two-part series, we study the components of the strategy pipeline, from
      clinical implementation to building enterprise solutions.

PMID- 29366599
TI  - The Effects of Fatigue From Overnight Shifts on Radiology Search Patterns and
      Diagnostic Performance.
AB  - PURPOSE: The aim of this study was to assess the effect of overnight shifts (ONS)
      on radiologist fatigue, visual search pattern, and diagnostic performance.
      METHODS: This experimental study was approved by the institutional review board.
      Twelve radiologists (five faculty members and seven residents) each completed two
      sessions: one during a normal workday ("not fatigued") and another in the morning
      after an ONS ("fatigued"). Each radiologist completed the Swedish Occupational
      Fatigue Inventory. During each session, radiologists viewed 20 bone radiographs
      consisting of normal and abnormal findings. Viewing time, diagnostic confidence,
      and eye-tracking data were recorded. RESULTS: Swedish Occupational Fatigue
      Inventory results demonstrated worsening in all five variables (lack of energy,
      physical exertion, physical discomfort, lack of motivation, and sleepiness) after
      ONS (P < .01). Overall, participants demonstrated worse diagnostic performance in
      the fatigued versus not fatigued state (P < .05). Total viewing time per case was
      longer when fatigued (35.9 +/- 25.8 seconds) than not fatigued (24.8 +/- 16.3
      seconds) (P < .0001). Total viewing time per case was longer for residents (P <
      .05). Mean total fixations generated during the search increased by 60% during
      fatigued sessions (P < .0001). Mean time to first fixate on the fracture
      increased by 34% during fatigued sessions (P < .0001) and was longer for
      residents (P < .01). Dwell times associated with true- and false-positive
      decisions increased, whereas those with false negatives decreased. CONCLUSIONS:
      After ONS, radiologists were more fatigued with worse diagnostic performance, a
      45% increase in view time per case, a 60% increase in total gaze fixations, and a
      34% increase in time to fixate on the fracture. The effects of fatigue were more
      pronounced in residents.

PMID- 29366600
TI  - Translational Radiomics: Defining the Strategy Pipeline and Considerations for
      Application-Part 1: From Methodology to Clinical Implementation.
AB  - Enterprise imaging has channeled various technological innovations to the field
      of clinical radiology, ranging from advanced imaging equipment and
      postacquisition iterative reconstruction tools to image analysis and computer
      aided detection tools. More recently, the advancements in the field of
      quantitative image analysis coupled with machine learning-based data analytics,
      classification, and integration have ushered us into the era of radiomics, which
      has tremendous potential in clinical decision support as well as drug discovery.
      There are important issues to consider to incorporate radiomics as a clinically
      applicable system and a commercially viable solution. In this two-part series, we
      offer insights into the development of the translational pipeline for radiomics
      from methodology to clinical implementation (Part 1) and from that to enterprise
      development (Part 2).

PMID- 29366601
TI  - The four-category classification of the urgency of caesarean sections in the UK
      needs vital improvements.

PMID- 29366602
TI  - Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to
      peripheral loss of Tregs.
AB  - Regulatory T cells are critical for the generation and maintenance of peripheral
      tolerance. Conditional deletion of the transcriptional repressor NKAP in Tregs
      using Foxp3-YFP-cre NKAP conditional knockout mice causes aggressive autoimmunity
      characterized by thymic atrophy, lymphadenopathy, peripheral T cell activation,
      generation of autoantibodies, immune infiltration into several organs, and crusty
      skin at 3 weeks of age, similar to that of "scurfy" Foxp3-mutant mice. While Treg
      development in the thymus proceeds normally in the absence of NKAP, there is a
      severe loss of thymically-derived Tregs in the periphery. NKAP-deficient Tregs
      have a recent thymic emigrant phenotype, and are attacked by complement in a cell
      intrinsic manner in the periphery. Previously, we demonstrated that NKAP is
      required for conventional T cell maturation as it prevents complement-mediated
      attack in the periphery. We now show that Tregs undergo a similar maturation
      process as conventional T cells, requiring NKAP to acquire complement resistance
      after thymic egress.

PMID- 29366603
TI  - Both left ventricular papillary muscles necrosis, an eosinophylic lymphoblastic
      leukemia revealed by endomyocardial fibrosis.

PMID- 29366604
TI  - [A retentional jaundice in a healthy sixty-seven year old man].

PMID- 29366605
TI  - The Definition of Open Reading Frame Revisited.
AB  - The term open reading frame (ORF) is of central importance to gene finding.
      Surprisingly, at least three definitions are in use. We discuss several molecular
      biological and bioinformatics aspects, and we recommend using the definition in
      which an ORF is bounded by stop codons.

PMID- 29366607
TI  - SOHO State of the Art Updates and Next Questions: Hodgkin Lymphoma.
AB  - Until recently, advances in classic Hodgkin lymphoma (HL) treatment primarily
      consisted of minor modifications of highly effective decades-old chemotherapy and
      radiation approaches. In early-stage disease, excellent outcomes have been
      reported with fewer cycles of chemotherapy, lower doses, smaller radiation fields
      and in some circumstances, radiation elimination. In advanced-stage disease,
      maintaining the dose intensity of standard chemotherapy regimens has resulted in
      modest improvements in outcomes. During the past decade, the use of early interim
      positron emission tomography (PET) scans to escalate or de-escalate treatment has
      been the subject of intense investigation with the goal of maximizing efficacy
      and minimizing toxicity. Important updates from recent PET-directed trials
      include; elimination of bleomycin in patients with advanced-stage HL and negative
      interim PET findings, the benefit of therapy escalation in patients with
      unfavorable early-stage HL and positive interim PET findings, and the minimal
      benefit of consolidative radiotherapy in patients with unfavorable early-stage HL
      and negative interim PET findings. A more nuanced approach to consolidative
      radiotherapy is required for patients with favorable early-stage disease based on
      age, disease sites, secondary cancer risk, and cardiovascular disease.
      Brentuximab vedotin and nivolumab/pembrolizumab have provided promising new
      options with surprisingly high response rates and modest toxicity for patients
      with relapsed HL whose disease does not respond to standard treatments.
      Incorporating these agents into earlier therapy is an area of active
      investigation for all stages of HL. Although the overall prognosis for HL
      patients has seen incremental improvement, efforts to optimize treatment with
      more effective and less toxic approaches continue.

PMID- 29366606
TI  - PRDM9 and Its Role in Genetic Recombination.
AB  - PRDM9 is a zinc finger protein that binds DNA at specific locations in the genome
      where it trimethylates histone H3 at lysines 4 and 36 at surrounding nucleosomes.
      During meiosis in many species, including humans and mice where PRDM9 has been
      most intensely studied, these actions determine the location of recombination
      hotspots, where genetic recombination occurs. In addition, PRDM9 facilitates the
      association of hotspots with the chromosome axis, the site of the programmed DNA
      double-strand breaks (DSBs) that give rise to genetic exchange between
      chromosomes. In the absence of PRDM9 DSBs are not properly repaired.
      Collectively, these actions determine patterns of genetic linkage and the
      possibilities for chromosome reorganization over successive generations.

PMID- 29366608
TI  - BTB/POZ domain-containing protein 7 is inversely associated with fibronectin
      expression in salivary adenoid cystic carcinoma.
AB  - OBJECTIVE: This study aimed to investigate the relationship between BTB/POZ
      domain-containing protein 7 (BTBD7) and fibronectin (FN) expression in salivary
      adenoid cystic carcinoma (SACC) and the function of BTBD7 in proliferation,
      migration, and invasion of SACC cells. STUDY DESIGN: The BTBD7 and FN expression
      in SACC and nontumor salivary tissues as well as SACC cells were characterized by
      immunohistochemistry and immunofluorescence. The effect of BTBD7 silencing on the
      proliferation, migration, and invasion of SACC-LM cells were determined by wound
      healing and transwell invasion assays. RESULTS: The percentages of SACC with
      positive BTBD7 expression were significantly higher than those of SACC with FN
      expression. BTBD7 silencing significantly increased the relative levels of FN
      expression and inhibited the proliferation, migration, and invasion of SACC-LM
      cells. CONCLUSIONS: The study data indicated that BTBD7 was inversely associated
      with FN expression in SACC. BTBD7 may inhibit FN expression, but it promotes the
      proliferation, migration, and invasion of SACC-LM cells. Hence, BTBD7 may be
      associated with metastasis and a new therapeutic target for intervention of SACC.

PMID- 29366609
TI  - Surgical treatment of enterovirus D68 brainstem encephalitis-induced dysphagia.
AB  - Cluster of acute flaccid paralysis and cranial nerve dysfunction was associated
      with a 2014 outbreak of enterovirus D68 (EV-D68) respiratory illness in US. We
      describe a 33 year-old male patient of refractory dysphagia due to EV-D68-induced
      brainstem encephalitis successfully treated by surgery. Following acute upper
      respiratory tract infection, he developed dysphagia and bilateral facial
      paralysis. A coughing reflex was readily produced when the laryngopharyngeal
      fiberscope touched the epiglottis, however, water infusion induced only very weak
      and slow swallowing reflex, suggesting that only motor component was impaired but
      sensory function was preserved during swallowing. Despite eight months
      conservative rehabilitations, Food Intake Level Scale (FILS) remained level 4.
      Therefore, corrective surgeries including cricopharyngeal myotomy, laryngeal
      suspension, and pharyngeal flap were performed. Thirty-six days after surgery,
      FILS rapidly and dramatically improved to level 8. This is the first report
      describing a successful surgical intervention for EV-D68-induced refractory
      dysphagia. Surgical treatment was suitable for EV-D68-induced dysphagia, perhaps
      because sensory function was preserved and only motor disturbance was present
      during the pharyngeal stage of swallowing.

PMID- 29366610
TI  - [Occiput posterior presentation at delivery: Materno-foetal outcomes and
      predictive factors of rotation].
AB  - OBJECTIVES: To describe the maternal and foetal outcomes of an occiput posterior
      foetal position at delivery; to evaluate predictive factors of anterior rotation
      during labour. METHODS: Descriptive retrospective analysis of a cohort of 439
      women with foetuses in occiput posterior position during labour. Logistic
      regression analysis to quantify the effect of factors that may favour anterior
      rotation. RESULTS: Most of foetuses (64%) do an anterior rotation during labour
      and 13% during the expulsive phase. The consequences of a persistent foetal
      occiput posterior position during delivery are a significantly increased average
      time of second stage labour compared to others positions (65.19minutes vs. 43.29,
      P=0.001, respectively); a higher percentage of caesarean sections (72.0% versus
      4.7%, P<0.001) and instrumental delivery (among low-birth deliveries, 60.7%
      versus 25.2%, P<0.001); more frequent third-degree perineal tears (14.3% vs.
      0.6%, P<0.001) and more abundant blood loss (560mL versus 344mL, P<0.001). In a
      multi-variable model including nulliparity, station of the presenting part and
      degree of flexion of the foetal head at complete dilatation, the only predictive
      factor independent of rotation at delivery is a good flexion of the foetal head
      at complete dilatation, which multiplies the anterior rotation probability by
      six. CONCLUSION: A good flexion of the foetal head is significantly associated
      with anterior rotation. Other studies exploring ways to increase anterior
      rotation during labour are needed to reduce the very high risk of caesarean
      section and instrumentation associated with the foetal occiput posterior
      position.

PMID- 29366611
TI  - Functional outcomes after prostatic cryosurgery.
AB  - OBJECTIVE: To assess the functional effects of prostatic cryosurgery on
      micturition. MATERIAL AND METHODS: Prospective study of men who underwent
      cryosurgery (CS) for prostate cancer between 2013 - 2015. Low urinary tract
      symptoms (LUTS) and quality of life (QoL) were assessed 1 month before surgery
      using IPSS questionnaire, a three-day voiding diary (3DVD) and uroflowmetry with
      ultrasound-measured postvoid residual volume. Need of medical treatment for LUTS
      was also recorded. The same assessment was performed at 3, 6 and 12 months after
      CS. Outcomes after surgery were compared to those prior to surgery. RESULTS:
      Forty-five patients underwent a CS during the study period, of whom 25 patients
      could be recruited in the study. Mean age was 73.5 years (range 66-84). Nineteen
      CS (76%) were performed as a primary procedure, while 6 CS (24%) as a salvage
      procedure. No statistical differences were found comparing results of IPSS, QoL,
      D3vd or uroflowmetry and PVR at 3, 6 or 12 months after CS compared to before
      surgery. Before CS, 8 (32%) patients were on medical treatment for LUTS, while at
      6 and 12 months after surgery, 3 (13.6%) and 2 (9.5%) patients required some
      medication, respectively. CONCLUSION: According to the punctuation of IPSS, QoL
      questionnaire, and a 3-day voiding diary, LUTS does not worsen after CS.
      Prostatic cryosurgery does not seem to impact uroflowmetry results.

PMID- 29366612
TI  - Accessibility Landscapes of Supplemental Nutrition Assistance Program-Authorized
      Stores.
AB  - BACKGROUND: The Supplemental Nutrition Assistance Program (SNAP) is the largest
      food assistance program in the United States. Participants receive electronic
      benefits that are redeemable at a variety of food stores. Previous research notes
      that low-income neighborhoods often lack supermarkets with high-quality,
      affordable food. OBJECTIVE: The first aim of this study was to explore the number
      and spatial distribution of SNAP stores by type and to assess how SNAP benefit
      redemption is linked to store type in North Carolina in 2015. The second aim was
      to compare the demographics of populations living in areas with a high
      concentration of SNAP participants vs areas with a lower concentration of SNAP
      participants. The third aim was to test for disparities in the availability of
      and access to SNAP-authorized stores in areas with high vs low concentration of
      SNAP participants stratified by rural/urban status. DESIGN: US Department of
      Agriculture and US Census data were used to explore the spatial distribution of
      SNAP stores at the census block group level utilizing a Geographic Information
      System. PARTICIPANTS: The 9,556 North Carolina SNAP stores in 2015 categorized
      into full-variety and limited-variety stores. OUTCOME MEASURES: Proximity to
      limited-variety SNAP food stores and full-variety SNAP food stores within access
      range (1 mile in urban areas and 10 miles in rural areas). STATISTICAL ANALYSES:
      Wilcoxon rank sum and chi2 tests are used to compare the distance to and
      concentration of SNAP stores by rurality and SNAP participant concentration at
      census block group scale. RESULTS: Among the SNAP stores in North Carolina, 83%
      are limited-variety stores and 17% are full-variety stores. There are disparities
      in the demographics of individuals living in census block groups with a high
      proportion of SNAP participants compared to census block groups with a lower
      proportion of SNAP participants. More households in higher SNAP participant
      census block groups were non-white, did not have a car, and had children compared
      to census block groups with lower SNAP participation. Residents in high SNAP
      participant census block groups typically had access to 0 full-variety stores and
      4 limited-variety stores in urban areas and 3 full-variety stores and 17 limited
      variety stores in rural areas. CONCLUSIONS: SNAP participant access to a variety
      of stores should be considered when approving food stores for SNAP authorization.
      More research is essential to disentangle the relationship between access to SNAP
      store type and SNAP food choice and to estimate geographical disparities.

PMID- 29366613
TI  - Keratoendotheliitis Fugax Hereditaria: A Novel Cryopyrin-Associated Periodic
      Syndrome Caused by a Mutation in the Nucleotide-Binding Domain, Leucine-Rich
      Repeat Family, Pyrin Domain-Containing 3 (NLRP3) Gene.
AB  - PURPOSE: To describe the phenotype and the genetic defect in keratoendotheliitis
      fugax hereditaria, an autosomal dominant keratitis that periodically affects the
      corneal endothelium and stroma, leading in some patients to opacities and
      decreased visual acuity. DESIGN: Cross-sectional, hospital-based study. METHODS:
      Patient Population: Thirty affected and 7 unaffected subjects from 7 families,
      and 4 sporadic patients from Finland. OBSERVATION PROCEDURES: Ophthalmic
      examination and photography, corneal topography, specular microscopy, and optical
      coherence tomography in 34 patients, whole exome sequencing in 10 patients, and
      Sanger sequencing in 34 patients. MAIN OUTCOME MEASURES: Clinical phenotype,
      disease-causing genetic variants. RESULTS: Unilateral attacks of
      keratoendotheliitis typically occurred 1-6 times a year (median, 2.5), starting
      at a median age of 11 years (range, 5-28 years), and lasted for 1-2 days. The
      attacks were characterized by cornea pseudoguttata and haze in the posterior
      corneal stroma, sometimes with a mild anterior chamber reaction, and got milder
      and less frequent in middle age. Seventeen (50%) patients had bilateral stromal
      opacities. The disease was inherited as an autosomal dominant trait. A likely
      pathogenic variant c.61G>C in the NLRP3 gene, encoding cryopyrin, was detected in
      all 34 tested patients and segregated with the disease. This variant is present
      in both Finnish and non-Finnish European populations at a frequency of about
      0.02% and 0.01%, respectively. CONCLUSION: Keratoendotheliitis fugax hereditaria
      is an autoinflammatory cryopyrin-associated periodic syndrome caused by a
      missense mutation c.61G>C in exon 1 of NLRP3 in Finnish patients. It is
      additionally expected to occur in other populations of European descent.

PMID- 29366614
TI  - Correlation Between Ischemic Index of Retinal Vein Occlusion and Oxygen
      Saturation in Retinal Vessels.
AB  - PURPOSE: To evaluate the relationship between the ischemic index and the oxygen
      saturation in retinal vessels in patients with retinal vein occlusion. DESIGN:
      Prospective, cross-sectional study. METHODS: We performed a prospective study.
      The cohort consisted of 43 eyes of 43 patients with retinal vein occlusions
      (RVO), 23 of whom had central retinal vein occlusions (CRVO) and 20 who had
      branch retinal vein occlusions (BRVO). We evaluated the retinal vessel saturation
      using an automatic retinal oximetry device. The retinal ischemic index (ISI) was
      determined using ultra-widefield fluorescein angiography. RESULTS: Mean arterial
      saturation (+/-SD) was 100% +/- 11%, mean vein saturation was 52% +/-13%, and
      mean A-V difference was 48% +/- 16% in eyes with BRVO. The average ISI in the
      same group was 0.48 (range 0-1). There was no statistically significant
      correlation between the retinal ischemic index and retinal saturation in the BRVO
      group. The affected eye in the CRVO group had a mean arterial saturation of 101%
      +/- 6%, vein saturation of 44% +/- 11 % and A-V difference of 58% +/- 10%. The
      average ISI in the CRVO group was 0.54 (range 0-1). A statistically significant
      negative correlation between ISI and vein saturation was found in the CRVO group
      (r = -0.686; P =.0003). A significant positive correlation between ISI and the A
      V difference was found in the CRVO group (r = 0.893; P <.0001). CONCLUSIONS:
      Oxygen saturation in the retinal vein and the arteriovenous difference correlated
      with the ischemic index in CRVO patients. No correlation was found for BRVO
      patients.

PMID- 29366615
TI  - The Evaluation and Management of Toxic Shock Syndrome in the Emergency
      Department: A Review of the Literature.
AB  - BACKGROUND: Toxic shock syndrome (TSS) is a severe, toxin-mediated illness that
      can mimic several other diseases and is lethal if not recognized and treated
      appropriately. OBJECTIVE: This review provides an emergency medicine evidence
      based summary of the current evaluation and treatment of TSS. DISCUSSION: The
      most common etiologic agents are Staphylococcus aureus and Streptococcus
      pyogenes. Sources of TSS include postsurgical wounds, postpartum, postabortion,
      burns, soft tissue injuries, pharyngitis, and focal infections. Symptoms are due
      to toxin production and infection focus. Early symptoms include fever, chills,
      malaise, rash, vomiting, diarrhea, and hypotension. Diffuse erythema and
      desquamation may occur later in the disease course. Laboratory assessment may
      demonstrate anemia, thrombocytopenia, elevated liver enzymes, and abnormal
      coagulation studies. Diagnostic criteria are available to facilitate the
      diagnosis, but they should not be relied on for definitive diagnosis. Rather,
      specific situations should trigger consideration of this disease process.
      Treatment involves intravenous fluids, source control, and antibiotics.
      Antibiotics should include a penicillinase-resistant penicillin, cephalosporin,
      or vancomycin (in methicillin-resistant S. aureus prevalent areas) along with
      either clindamycin or linezolid. CONCLUSION: TSS is a potentially deadly disease
      requiring prompt recognition and treatment. Focused history, physical
      examination, and laboratory testing are important for the diagnosis and
      management of this disease. Understanding the evaluation and treatment of TSS can
      assist providers with effectively managing these patients.

PMID- 29366616
TI  - Suffering in Silence: Medical Error and its Impact on Health Care Providers.
AB  - BACKGROUND: All humans are fallible. Because physicians are human, unintentional
      errors unfortunately occur. While unintentional medical errors have an impact on
      patients and their families, they may also contribute to adverse mental and
      emotional effects on the involved provider(s). These may include burnout, lack of
      concentration, poor work performance, posttraumatic stress disorder, depression,
      and even suicidality. OBJECTIVES: The objectives of this article are to 1)
      discuss the impact medical error has on involved provider(s), 2) provide
      potential reasons why medical error can have a negative impact on provider mental
      health, and 3) suggest solutions for providers and health care organizations to
      recognize and mitigate the adverse effects medical error has on providers.
      DISCUSSION: Physicians and other providers may feel a variety of adverse emotions
      after medical error, including guilt, shame, anxiety, fear, and depression. It is
      thought that the pervasive culture of perfectionism and individual blame in
      medicine plays a considerable role toward these negative effects. In addition,
      studies have found that despite physicians' desire for support after medical
      error, many physicians feel a lack of personal and administrative support. This
      may further contribute to poor emotional well-being. Potential solutions in the
      literature are proposed, including provider counseling, learning from mistakes
      without fear of punishment, discussing mistakes with others, focusing on the
      system versus the individual, and emphasizing provider wellness. Much of the
      reviewed literature is limited in terms of an emergency medicine focus or even
      regarding physicians in general. In addition, most studies are survey- or
      interview-based, which limits objectivity. While additional, more objective
      research is needed in terms of mitigating the effects of error on physicians,
      this review may help provide insight and support for those who feel alone in
      their attempt to heal after being involved in an adverse medical event.
      CONCLUSIONS: Unintentional medical error will likely always be a part of the
      medical system. However, by focusing on provider as well as patient health, we
      may be able to foster resilience in providers and improve care for patients in
      healthy, safe, and constructive environments.

PMID- 29366617
TI  - Colic Ischemia Precipitated by Gastrocolic Ligament Hematoma Onset after
      Gastroscopy.

PMID- 29366618
TI  - An Impaled Potential Unexploded Device in the Civilian Trauma Setting: A Case
      Report and Review of the Literature.
AB  - BACKGROUND: The management of patients with impaled unexploded devices is rare in
      the civilian setting. However, as the lines of the traditional battlefield are
      blurred by modern warfare and terrorist activity, emergency providers should be
      familiar with facility protocols, plans, and contact information of their local
      resources for unexploded devices. CASE REPORT: A 44-year-old male sustained a
      close-proximity blast injury to his lower extremities while manipulating a mortar
      type firework. He presented to the regional trauma center with an open,
      comminuted distal femur fracture and radiographic evidence of a potential
      explosive device in his thigh. His management was coordinated with the local
      Explosive Ordinance Disposal and the fire department. WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: Explosive devices pose a grave threat when
      encountered. Familiarization with protocols to manage these patients can mitigate
      disaster. Emergency providers should expect and be prepared to coordinate care
      for these patients.

PMID- 29366619
TI  - Encephaloduroateriosynangiosis versus conservative treatment for patients with
      moyamoya disease at late Suzuki stage.
AB  - The purpose of this study is to investigate the long-term outcomes after
      conservative and encephaloduroateriosynangiosis procedures for patients with
      moyamoya disease at late Suzuki stage. We retrospectively reviewed 64 patients
      (128 hemispheres) with moyamoya disease at late Suzuki Stage at Beijing Tiantan
      Hospital. Clinical features, radiologic findings, and outcomes were analyzed. The
      mean age at diagnosis was 29.0 +/- 14.9 years. The distribution of the initial
      Suzuki stage of MMD was as follows: stage 4, n = 75; stage 5, n = 46; stage 6, n
      = 7, PCA involvement was observed in 4 (37.5%) hemispheres. The incidence of
      postoperative stroke was 6.7%. During the average follow-up of 46.9 +/- 21.1
      months, including postoperative and follow-up strokes, seven of 75 (9.3%)
      conservatively treated hemispheres and 10 of 87 (10.1%) surgically treated
      patients experienced a stroke event there was not statistically significant in
      the Kaplan-Meier curve of stroke incidence between the surgical group and
      conservative group (log-rank test, p = .848). However, the rate of perfusion
      improvement in indirect bypass surgically treated patients was higher than in
      those conservative treated patients 3 months after discharge (p < .05). Although
      indirect bypass surgery was shown to be effective in improving the cerebral
      perfusion in patients with MMD at late Suzuki stage, it failed to reduce the risk
      of recurrent stroke compared to conservative treatment. Further study is needed
      to determine whether direct bypass surgery is effective in MMD patients at late
      Suzuki stage.

PMID- 29366620
TI  - Changes in hormones of the hypothalamic-pituitary-gonadal axis in migraine
      patients.
AB  - The incidence of migraine is higher in women than in men. Abnormality of the
      hypothalamus-pituitary-gonadal (HPG) axis is believed to be implicated in the
      pathogenesis of migraine. The aim of this study was to detect serum hormone
      levels in the HPG axis of migraineurs and analyze the relationship between the
      hormone levels and migraine-related clinical characteristics. One hundred and
      nineteen migraineurs were enrolled. Serum FSH, LH, estradiol, progesterone,
      testosterone, prolactin and GnRH was detected. Pain intensity and migraine
      related disability were evaluated using the visual analogue scale (VAS) and the
      Migraine Disability Assessment questionnaire (MIDAS). The relationships between
      sex hormone levels and the VAS score and the MIDAS score were also examined.
      Progesterone levels in male migraineurs were lower than those in healthy controls
      (P < .01). In female patients, in the follicular phase, testosterone levels were
      lower than in healthy controls (P < .01). In the luteal phase, estrogen and
      testosterone levels (P < .05) were lower than in healthy controls. Progesterone
      and testosterone levels (P < .01) were lower than in healthy controls in the
      postmenopausal phase. In male patients, estrogen levels were negatively
      associated with the MIDAS score (r = -0.602). In female patients, in the
      follicular phase, estrogen levels were positively correlated with headache
      duration and VAS score (r = 0.374, r = 0.331, respectively) and negatively
      related with MIDAS score (r = -0.334). In the luteal phase, estrogen and
      progesterone levels were negatively correlated with the MIDAS score (r = -0.772,
      r = -0.464, respectively). The levels of HPG axis hormones were abnormal in
      migraineurs and were associated with migraine-related clinical characteristics.

PMID- 29366621
TI  - High-resolution diffusion tensor-imaging indicates asymmetric microstructural
      disorganization within substantia nigra in early Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Parkinson's disease (PD) is characterised by
      neuropathological degenerative changes in the substantia nigra (SN). Our study
      aimed to evaluate whether high-resolution diffusion tensor-imaging (DTI) can
      detect anatomical biomarkers in early-stage PD, and has the potential to
      visualize asymmetry effects comparable to the 123I-FP-CIT SPECT (DaTSCAN).
      METHODS: Ten early-stage PD patients with mild disease severity and ten age- and
      gender-matched healthy controls were examined with a high-resolution DTI protocol
      at a 3 Tesla MRI scanner to assess fractional anisotropy (FA) values in the
      ventral, middle and dorsal region of SN. In addition, a subgroup of 5 PD patients
      underwent a DaTSCAN. RESULTS: PD subjects showed reduced FA values in all SN
      regions compared to controls, but post hoc analysis revealed a significant
      reduction (p = .032) in the dorsal region. There was no significant correlation
      between clinical data and FA values. Subgroup analysis of PD patients with
      asymmetric radioligand uptake in the DaTSCAN demonstrated also significant
      asymmetric FA values (p = .027) in the dorsal region of SN. CONCLUSIONS: Our
      results provide preliminary evidence that high-resolution DTI can detect in early
      stage PD patients with mild disease severity an anatomical biomarker in the
      dorsal region of SN, indicating microstructural disorganization. This biomarker,
      discriminating potentially in vivo between patients and healthy people, could be
      valuable for early PD diagnosis. If asymmetric radioligand uptake in the DaTSCAN
      was present, also asymmetry effects in the dorsal region of SN were obtained by
      DTI. These findings might contribute to improve effectiveness in diagnosing and
      monitoring PD.

PMID- 29366622
TI  - Resection of the largest reported hepatic small vessel neoplasm.
AB  - Hepatic small vessel neoplasm (HSVN) is a recently described vascular neoplasm of
      the adult liver. The neoplastic cells are positive for markers of vascular
      lineage (CD31, CD34, FLI-1). The distinctive morphology and infiltrative borders
      separate HSVN from benign vascular tumors such as cavernous hemangioma, while
      lack of atypical morphologic features, low to absent mitotic activity and low
      proliferation index distinguish it from malignant vascular tumors such as
      epithelioid hemangioendothelioma and angiosarcoma. Due to its infiltrative nature
      and lack of adequate follow-up information, the benign versus low-grade nature of
      this tumor is currently uncertain. We present a patient with resected HSVN
      involving all but the right posterior section of the liver, making this case the
      largest reported in the current literature.

PMID- 29366623
TI  - Perception of the level of preparation of intensive care personnel on the self
      protection plans.

PMID- 29366624
TI  - Ghrelin is expressed in the pregnant mammary glands of dairy goats and promotes
      the cell proliferation of mammary epithelial cells.
AB  - Little is known about ghrelin's effects on cell proliferation in pregnant mammary
      epithelial cells (MECs) even though it is known to be a mitogen for a variety of
      other cell types. The objectives of this study were to evaluate the expression
      and localization of ghrelin and its functional receptor, GHSR-1a, in the mammary
      glands of dairy goats during pregnancy and to investigate the direct role of
      ghrelin in cell proliferation of primary cultured MECs. Compared to the early
      stage (days 30) of pregnancy, the abundance of transcripts and protein of ghrelin
      and GHSR-1a were significantly greater in mid- and late-phases (between days 90
      and days 120) of pregnancy (p < .05). Immunohistochemistry analysis showed that
      ghrelin and GHSR-1a were predominantly localized in the alveolar and ductal
      mammary epithelial cells at various stages of pregnancy. In our in vitro
      experiments, ghrelin induced a dose- and time-dependent promotory effect on cell
      proliferation of MECs. At the dose of 103 pg/mL treatment 24 h, ghrelin augmented
      the expression of proliferation-related peptides (PCNA and cyclin B1).
      Furthermore, ghrelin promoted the expression of prolactin (PRL) and GHSR-1a in
      cultured MECs. Additionally, the stimulatory effects of ghrelin were blocked by d
      Lys3-GHRP6, a selective antagonist of GHSR-1a. As the temporal changes in ghrelin
      and GHSR-1a expression in pregnant goat mammary glands coincided with the mammary
      growth and development during the pregnancy, activation of GHSR-1a signal
      transduction pathways by ghrelin may play a direct role in the regulation of
      mammary growth in dairy goats.

PMID- 29366625
TI  - Involvement of mGluR I in EphB/ephrinB reverse signaling activation induced
      retinal ganglion cell apoptosis in a rat chronic hypertension model.
AB  - EphB/ephrinB reverse signaling is involved in retinal ganglion cell (RGC)
      apoptosis in experimental glaucoma. Here, we further investigated the mechanisms
      underlying EphB/ephrinB reverse signaling activation induced RGC apoptosis in a
      rat chronic ocular hypertension (COH) model, using patch-clamp techniques in
      retinal slices. In COH retinas, RGCs showed higher spontaneous firing frequency
      and much more depolarized membrane potential as compared to control, which was
      mimicked by intravitreally injection of EphB2-Fc, an activator of ephrinB2. The
      changes in RGC spontaneous firing and membrane potential could be reversed by the
      tyrosine kinase inhibitor PP2, suggesting that EphB/ephrinB reverse signaling
      activation induced RGC hyperexcitability. Intravitreal pre-injection of either
      LY367385 or MPEP, selective mGluR1 and mGluR5 antagonists, also blocked the
      changes in RGC spontaneous firing and membrane potential. Co-immunoprecipitation
      experiments showed an interaction between ephrinB2 and group I metabotropic
      glutamate receptor (mGluR I) (mGluR1/mGluR5). Furthermore, intravitreal pre
      injection of the mixture of L-NAME (an NO synthase inhibitor) and XPro1595 (a
      selective inhibitor of soluble TNF-alpha) could reduce the EphB2-Fc injection
      induced increase in RGC firing, suggesting that Muller cells might be involved in
      EphB/ephrinB reverse signaling activation induced change in RGC
      hyperexcitability. In addition, LY367385/MPEP reduced the numbers of TUNEL
      positive RGCs both in EphB2-Fc injected and COH retinas. All results suggest that
      activation of EphB/ephrinB reverse signaling induces RGC hyperexcitability and
      apoptosis by interacting with mGluR I in COH rats. Appropriate reduction of
      EphB/ephrinB reverse signaling could alleviate the loss of RGCs in glaucoma.

PMID- 29366626
TI  - Hunger, ghrelin and the gut.
AB  - Hunger is defined as a craving or urgent need for food. Abundant evidence now
      indicates that homeostatic and cognitive mechanisms promote the sensation of
      hunger. Communication between the gastrointestinal (GI) tract and the central
      nervous system (CNS) regulate both homeostatic and cognitive mechanisms to
      control feeding behavior. In this context the GI derived feeding peptide ghrelin,
      targets the CNS to promote food anticipation, learning, hedonic feeding and
      motivation for food. Importantly meal expectation following nutrient deprivation
      or satiation is associated with elevation of plasma ghrelin, highlighting the
      propensity of each mechanism to stimulate GI ghrelin secretion. It is well
      established that multiple physiological processes control ghrelin secretion from
      the GI tract. For example activation of descending sympathetic and
      parasympathetic pathways, GI feeding peptides, metabolic factors and
      endocannabinoid signaling mechanisms all regulate ghrelin secretion. In parallel,
      activation of the CNS ghrelin receptor (GHSR-1a) controls food anticipation, food
      based learning, spatial learning and the rewarding properties of food. Notably
      GHSR-1a is expressed within a network of CNS regions that regulate diverse
      aspects of feeding behavior. These examples suggest a redundancy regarding
      mechanisms that control GI ghrelin secretion and complexity for GHSR-1a-mediated
      regulation of food intake. Based on this collective data, we suggest that learned
      information linked to the receipt of food is transmitted from the CNS to the GI
      tract to stimulate ghrelin release. We further postulate that GI ghrelin release
      and ghrelin-GHSR-1a interactions adapt over time, metabolic status and
      environment to direct feeding behavior.

PMID- 29366627
TI  - Enhanced Immunosuppressive Properties of Human Mesenchymal Stem Cells Primed by
      Interferon-gamma.
AB  - Mesenchymal stem cells (MSCs) are of particular interest for the treatment of
      immune-related diseases owing to their immunosuppressive properties. In this
      study, we aimed to identify the effect of interferon (IFN)-gamma priming on
      immunomodulation by MSCs and elucidate the possible mechanism underlying their
      properties for the clinical treatment of allogeneic conflicts. Infusion of MSCs
      primed with IFN-gamma significantly reduced the symptoms of graft-versus-host
      disease (GVHD) in NOD-SCID mice, thereby increasing survival rate when compared
      with naive MSC-infused mice. However, infusion of IFN-gamma-primed MSCs in which
      indoleamine 2,3-dioxygenase (IDO) was downregulated did not elicit this effect.
      The IDO gene was expressed in MSCs via the IFN-gamma-Janus kinase (JAK)-signal
      transducer and activator of transcription 1 (STAT1) pathway, and the infusion of
      IDO-over-expressing MSCs increased survival rate in an in vivo GVHD model,
      similar to infusion of IFN-gamma-primed MSCs. These data indicate that IFN-gamma
      production by activated T-cells is correlated with the induction of IDO
      expression in MSCs via the IFN-gamma-JAK-STAT1 pathway, which in turn results in
      the suppression of T-cell proliferation. Our findings also suggest that cell
      therapy based on MSCs primed with IFN-gamma can be used for the clinical
      treatment of allogeneic conflicts, including GVHD.

PMID- 29366629
TI  - Comparison of six commercial tick-borne encephalitis IgM and IgG ELISA kits and
      the molecular characterization of their antigenic design.
AB  - Tick-borne encephalitis virus (TBEV) diagnosis is mainly based on the detection
      of viral-specific antibodies in serum. Several commercial assays are available,
      but published data on their performance remain unclear. We assessed six IgM and
      six IgG commercial enzyme-linked immunosorbent assay (ELISA) kits (ELISA-1
      through ELISA-6) using 94 samples, including precharacterized TBEV-positive
      samples (n=50) and -negative samples (n=44). The six manufacturers showed
      satisfactory sensitivity and specificity and high overall agreement for both IgM
      and IgG. Three manufacturers showed better reproducibility and were the most
      sensitive (100%) and specific (95.5-98.1%) for both IgM and IgG. Two of them were
      also in agreement with the clinical interpretation in more than 90% of the cases.
      All the assays use inactivated virus as antigen, with strains showing
      approximately 94% homology at the amino acid level. The antigenic format of the
      assays was discussed to further improve this TBEV diagnostic tool.

PMID- 29366628
TI  - Organ-specific mechanisms linking innate and adaptive antifungal immunity.
AB  - Fungal infections remain a significant global health problem in humans. Fungi
      infect millions of people worldwide and cause from acute superficial infections
      to life-threatening systemic disease to chronic illnesses. Trying to decipher the
      complex innate and adaptive immune mechanisms that protect humans from pathogenic
      fungi is therefore a key research goal that may lead to immune-based therapeutic
      strategies and improved patient outcomes. In this review, we summarize how the
      cells and molecules of the innate immune system activate the adaptive immune
      system to elicit long-term immunity to fungi. We present current knowledge and
      exciting new advances in the context of organ-specific immunity, outlining the
      tissue-specific tropisms for the major pathogenic fungi of humans, the antifungal
      functions of tissue-resident myeloid cells, and the adaptive immune responses
      required to protect specific organs from fungal challenge.

PMID- 29366630
TI  - An advanced uracil DNA glycosylase-supplemented loop-mediated isothermal
      amplification (UDG-LAMP) technique used in the sensitive and specific detection
      of Cryptosporidium parvum, Cryptosporidium hominis, and Cryptosporidium
      meleagridis in AIDS patients.
AB  - The rapid and accurate detection of Cryptosporidium spp. is critically important
      for the prevention and timely treatment of cryptosporidiosis in AIDS patients
      (APs). This study was conducted to examine a UDG-LAMP technique for the first
      time to diagnose cryptosporidiosis in APs. After collecting demographic and
      clinical data, three stool samples were collected from the participants (120
      volunteering APs). The microscopic examination of stained smears using the acid
      fast method and the UDG-LAMP assay were performed for each sample. 10% of APs
      were infected with Cryptosporidium spp. The number of detected cryptosporidiosis
      cases using the acid-fast staining and UDG-LAMP methods were significantly
      different (P < 0.001). Diarrhea and weight loss were found to be significantly
      associated with cryptosporidiosis in patients (P < 0.05). The pretreatment of
      LAMP reagents with UDG successfully eliminated the likelihood of product re
      amplification remaining from previous reactions. The UDG-LAMP technique could
      detect cryptosporidiosis in APs with high sensitivity and rapidity without
      carryover contamination.

PMID- 29366631
TI  - Preoperative evaluation of intraoperative blood loss during malignant soft tissue
      tumor resection by ultrasonography.
AB  - BACKGROUND: Preoperative evaluation of the risk of surgery-related blood loss in
      malignant soft tissue tumor resection is difficult because of wide variations in
      histological subtype, malignancy, location, and size. Ultrasonography is useful
      for the evaluation of blood flow around a soft tissue tumor and has the potential
      to preoperatively estimate intraoperative blood loss in tumor resection. To date,
      there has been no report regarding blood loss evaluation using ultrasonography in
      this field. PATIENTS AND METHODS: The usefulness of information obtained by
      ultrasonography, including tumor size, vessel density in the tumor, and blood
      flow volume in the vessels, was analyzed for the prediction of intraoperative
      blood loss in malignant soft tissue tumor resection. RESULTS: Vessel density in
      the tumor and blood flow in the vessels were identified as independent risk
      factors for blood loss. Using these factors, a new index for the prediction of
      blood loss was established. Receiver operating characteristic analyses revealed a
      high area under the curve value (0.80), confirming the accuracy of the index for
      the prediction of blood loss. CONCLUSION: Ultrasonography is a useful modality
      for predicting intraoperative blood loss in malignant soft tissue tumor surgery.

PMID- 29366632
TI  - Prognostic and Therapeutic Implications of Circulating Androgen Receptor Gene
      Copy Number in Prostate Cancer Patients Using Droplet Digital Polymerase Chain
      Reaction.
AB  - BACKGROUND: Resistance mechanisms in the androgen receptor (AR) signaling pathway
      remain key drivers in the progression to castration-resistant prostate cancer
      (CRPC) and relapse under antihormonal therapy. MATERIALS AND METHODS: We
      evaluated the circulating AR gene copy number (CN) gain using droplet digital
      polymerase chain reaction in 21 control and 91 prostate cancer serum samples and
      its prognostic and therapeutic implications in prostate cancer. RESULTS: In CRPC,
      AR CN gain was associated with faster progression to CRPC (P = .026), a greater
      number of previous treatments (P = .045), and previous chemotherapy (P = .016).
      Comparing patients with and without CN gain, the median progression-free survival
      (PFS) in the abiraterone subgroup was 1.7 months versus not reached (P = .004),
      and the median overall survival (OS) was 7 months versus 20.9 months (P = .020).
      In the enzalutamide subgroup, PFS was 1.7 versus 10.8 months (P = .006), and OS
      was 6.1 versus 16.5 months (P = .042). In the taxane subgroup, PFS was 3.2 versus
      6.5 months (P = .093), and OS was 3.9 months versus not reached (P = .026). The
      presence of more AR copies correlated with shorter androgen deprivation (P =
      .002), abiraterone (P = .022), enzalutamide (P = .008), and taxane (P = .039)
      therapy. CONCLUSION: Circulating AR CN gain predicts for a poor prognosis in
      CRPC. It is a promising biomarker predetermining rapid CRPC progression and
      predicting worse abiraterone and enzalutamide outcomes. Furthermore, it is
      associated with multiple previous treatments and previous chemotherapy.

PMID- 29366633
TI  - Prognostic Value of Pretreatment Albumin-to-Globulin Ratio in Patients With Non
      Muscle-Invasive Bladder Cancer.
AB  - PURPOSE: To investigate the relationship between albumin-to-globulin ratio (AGR)
      and oncologic outcomes in patients with non-muscle-invasive bladder cancer
      (NMIBC). PATIENTS AND METHODS: We identified 364 patients with primary NMIBC who
      underwent transurethral surgery between 2000 and 2015. The association between
      pretreatment AGR and clinicopathologic variables, including oncologic outcomes,
      was statistically evaluated. RESULTS: One hundred twenty patients (33.0%)
      experienced at least one tumor recurrence, and 23 (6.3%) developed muscle
      invasive disease. The median (interquartile range) pretreatment AGR was 1.73
      (1.53-1.89). The Kaplan-Meier curve revealed that tumor recurrence was strongly
      predicted in patients with pretreatment AGR < 1.6, and similar results were
      observed for disease progression (P < .01 and P < .01, respectively). On
      multivariate analysis, we found that pretreatment AGR < 1.6 is an independent
      risk factor for tumor recurrence (hazard ratio, 0.53; P < .01). On univariate
      analysis, pretreatment AGR < 1.6 was also associated with disease progression
      (hazard ratio, 0.24; P < .01). CONCLUSION: Low pretreatment AGR is an independent
      risk factor for tumor recurrence and is one risk factor for disease progression
      in NMIBC patients. This inexpensive and easily accessible biomarker may become
      useful in selecting patients with NMIBC with higher risk of recurrence and
      progression.

PMID- 29366635
TI  - [Evaluation of adherence and satisfaction with intermittent catheterization in
      children: Feasibility and first steps of validation of InCaSaQ and ICAS in the
      pediatric population].
AB  - INTRODUCTION: In pediatric neurourology, clean intermittent catheterization (CIC)
      setting, and then self catheterization learning are important steps for children
      with neurogenic bladder. There is no adherence and satisfaction evaluation scale
      for children who are using self or hetero CIC. The aim of this article is to
      study the feasibility of using InCaSaQ (Intermittent Catheterization Satisfaction
      Questionnaire) and ICAS (Intermittent Catheterization Adherence Scale) in
      children, and to validate the first steps. PATIENTS AND METHODS: Scale validation
      monocentric study. Inclusion criterias were patients with neurogenic bladder,
      under the age of 18, using CIC (auto or hetero). The questionnaires ICAS and
      InCaSaQ were sent twice between 2017 March and April, and then filled by the
      child or his parents depending on who was doing the CIC. The internal concistency
      (Cronbach's alpha) measured the construct validity. The reproductibility was
      measured by the intraclass correlation coefficient (ICC) and the Wilcoxon and
      McNemar tests. Filling facility was evaluated for each score (evaluation with a 0
      to 10 scale from the person who filled the questionnaire). RESULTS: Twenty two
      patients were included, and 50 questionnaires filled (25 ICAS and 25 InCaSaQ),
      twice each. Internal consistency was good for InCaSaQ (Cronbach's alpha>0,7) and
      so was ICAS and InCaSaQ reproductibility (ICC>0,7 for most of the questions).
      Patients under hetero-CIC had a worse adherence than parents of children under
      hetero-CIC (ICAS 3,25 versus 0,7 for children under hetero-CIC). The lowest
      InCaSaQ item was the way of throwing away their catheter. CONCLUSIONS: ICAS and
      InCaSaQ are interesting tools which can be used for children under auto and
      hetero-CIC. Studies with more patients will be necessary for finalizing the
      validation of these scales in the pediatric population. LEVEL OF PROOF: 4.

PMID- 29366634
TI  - [Postoperative C-reactive protein is a reliable marker to detect complications
      after radical cystectomy].
AB  - PURPOSE: Postoperative serum C-reactive protein (CRP) can be measured after major
      abdominal surgery to predict of complications at postoperative day (POD) 4.
      However, in urology, no studies have been conduced to analyze the role of CRP
      after radical cystectomy. The present study aims to analyze the relationship
      between a high postoperative level of CRP and the presence of complications after
      radical cystectomy for cancer. MATERIALS AND METHODS: This multicenter
      retrospective study included 313 patients treated with radical cystectomy for
      cancer between January 2013 and July 2016. Among the patients, 57.5% of patients
      received urinary diversion using a Bricker ileal conduit, 30.5% an orthotropic
      ileal neobladder, and 11.5% had an ureterocutaneostomy. RESULTS: Three hundred
      and thirteen patients were included (mean age 68.1+/-9.2 years). Among the
      patients, 26.5% had grade>=2 complications, according to the Clavien-Dindo
      classification. In multivariate analysis, only CRP level at POD 4 predicted the
      risk of a complication (P<0.001). CRP>150mg/L at POD 4 was strongly associated
      with a risk of a postoperative complication after a cystectomy (OR=81.42, 95% CI
      [25.6-258.3], P<0.001). CRP assessed on POD4 was reliable at ruling out the
      existence of an infectious complications with a negative predictive value of
      0.94. The main limitation of our study was it observational design. CONCLUSIONS:
      CRP at POD4 with a threshold of 150mg/L would reliably predict the risk of
      postoperative complications after cystectomy. Monitoring postoperative CRP could
      help adapt rehabilitation protocols after radical cystectomy and also the early
      management of complications.

PMID- 29366636
TI  - Mechanism of Inhibition of Translation Termination by Blasticidin S.
AB  - Understanding the mechanisms of inhibitors of translation termination may inform
      development of new antibacterials and therapeutics for premature termination
      diseases. We report the crystal structure of the potent termination inhibitor
      blasticidin S bound to the ribosomal 70S*release factor 1 (RF1) termination
      complex. Blasticidin S shifts the catalytic domain 3 of RF1 and restructures the
      peptidyl transferase center. Universally conserved uridine 2585 in the peptidyl
      transferase center occludes the catalytic backbone of the GGQ motif of RF1,
      explaining the structural mechanism of inhibition. Rearrangement of domain 3
      relative to the codon-recognition domain 2 provides insight into the dynamics of
      RF1 implicated in termination accuracy.

PMID- 29366637
TI  - A prospective single-institute study of the impact of Daikenchuto on the early
      postoperative outcome after living donor liver transplantation.
AB  - BACKGROUND: The aim of this study was to investigate the impact of Daikenchuto
      (DKT) on early postoperative outcomes after living donor liver transplantation
      (LDLT), focusing on the prevention of abdominal distension and bacterial
      translocation. METHODS: Adult LDLT recipients were prospectively divided into 2
      groups, who were administered DKT (n = 20, group A) or not (n = 20, group B). The
      area of bowel gas defined as gas volume score (GVS) 7 days after LDLT was
      calculated. Postoperative liver function tests, the development of bacterial,
      viral, and fungal infections, and GVS after LDLT were reviewed. RESULTS: There
      were no significant differences in liver function tests and ammonia level after
      LDLT. Also, the rates of infection and the result of culture study were not
      different between groups. The median GVS 7 days after LDLT was not significantly
      different between groups A (0.26 (range, 0.12-0.58)) and B (0.23 (range, 0.15
      0.42)). CONCLUSIONS: No positive impact was observed for 14-day DKT
      administration after LDLT, in terms of preventing infection or abdominal
      distension.

PMID- 29366638
TI  - 3,4-diaminopyridine reverses paralysis in botulinum neurotoxin-intoxicated
      diaphragms through two functionally distinct mechanisms.
AB  - Botulinum neurotoxins (BoNTs) are exceedingly potent neurological poisons that
      prevent neurotransmitter release from peripheral nerve terminals by cleaving
      presynaptic proteins required for synaptic vesicle fusion. The ensuing
      neuromuscular paralysis causes death by asphyxiation. Although no antidotal
      treatments exist to block toxin activity within the nerve terminal, aminopyridine
      antagonists of voltage-gated potassium channels have been proposed as symptomatic
      treatments for botulism toxemia. However, clinical evaluation of aminopyridines
      as symptomatic treatments for botulism has been inconclusive, in part because
      mechanisms responsible for reversal of paralysis in BoNT-poisoned nerve terminals
      are not understood. Here we measured the effects of 3,4-diaminopyridine (DAP) on
      phrenic nerve-elicited diaphragm contraction and end-plate potentials at various
      times after intoxication with BoNT serotypes A, B, or E. We found that DAP
      mediated increases in quantal content promote neurotransmission from intoxicated
      nerve terminals through two functionally distinguishable mechanisms. First, DAP
      increases the probability of neurotransmission at non-intoxicated release sites.
      This mechanism is serotype-independent, becomes less effective as nerve terminals
      become progressively impaired, and remains susceptible to ongoing intoxication.
      Second, DAP elicits persistent production of toxin-resistant endplate potentials
      from nerve terminals fully intoxicated by BoNT/A, but not serotypes B or E. Since
      this effect appears specific to BoNT/A intoxication, we propose that DAP
      treatment enables BoNT/A-cleaved SNAP-25 to productively engage in fusogenic
      release by increasing the opportunity for low-efficiency fusion events. These
      findings have important implications for DAP as a botulism therapeutic by
      defining conditions under which DAP may be clinically effective in reversing
      botulism symptoms.

PMID- 29366639
TI  - Combined effects of simultaneous exposure to six phthalates and emulsifier
      glycerol monosterate on male reproductive system in rats.
AB  - Human beings are inevitably exposed to ubiquitous phthalate esters (PEs), and
      simultaneously ingesting high quantities of food emulsifiers via daily diet.
      Glycerin monostearate (GMS) is a widely used food emulsifier. The purposes of
      this study were to investigate the combined effects between the mixture of six
      frequently used PEs (MIXPs) and GMS on male rat reproductive system, and further
      to explore the underlying mechanisms. Male rats were orally administered either
      sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses
      with or without GMS (200mg/kg/d) by gavage. The 15-week exposure of MIXPs caused
      male reproductive toxicity in a dose- and time-dependent manner, including the
      decrease of serum testosterone and morphological damage of testis. Metabonomics
      analyses of urine and Western blotting analyses of steroidogenic proteins (StAR,
      P450scc, CYP17A1, 17beta-HSD and P450arom) indicated that MIXPs exposure down
      regulated the expression of steroidogenic proteins, and might alter androgen
      metabolism. The results also showed that the presence of GMS exacerbated the
      toxicities of MIXPs to male rat reproductive system. These findings suggest that
      food emulsifier GMS could enhance the toxic effects of MIXPs on male hormone
      biosynthesis.

PMID- 29366640
TI  - Value of Intact Prostate Specific Antigen and Human Kallikrein 2 in the 4
      Kallikrein Predictive Model: An Individual Patient Data Meta-Analysis.
AB  - PURPOSE: The 4 kallikrein panel, commercially available as the 4Kscore(r), is a
      statistical model that has been shown to accurately predict Gleason Grade Group 2
      or greater (high grade) cancer on biopsy and the long-term risk of distant
      prostate cancer metastases. The panel includes 2 novel markers, namely intact
      prostate specific antigen and hK2. It has been questioned whether these 2
      additional markers add discrimination to the clinical predictors of patient age,
      digital rectal examination and prior biopsy, and the established molecular
      markers total and free prostate specific antigen. MATERIALS AND METHODS: We
      performed an individual patient data meta-analysis of published studies in which
      the 4 kallikrein panel was measured in men undergoing prostate biopsy. We assess
      the improvement in discrimination associated with including intact prostate
      specific antigen and hK2 along with total and free prostate specific antigen in
      the statistical model. RESULTS: Included in analysis were 14,510 men from a total
      of 10 studies. The fixed effects meta-analytical estimate of the discrimination
      of the model without intact prostate specific antigen and hK2 was 0.742 (95% CI
      0.727-0.756) compared to 0.813 (95% CI 0.801-0.825) for the full kallikrein
      model. The 95% CIs did not overlap and the difference in discrimination was
      highly statistically significant (0.069, 95% CI 0.057-0.080, p <0.0001). Intact
      prostate specific antigen (increase in discrimination 0.059, 95% CI 0.050-0.069)
      and hK2 (increase in discrimination 0.024, 95% CI 0.020-0.029, each p <0.0001)
      added independently to the model. CONCLUSIONS: The clinical value of the panel
      could not be replicated using data readily available to urologists without
      measuring intact prostate specific antigen and hK2.

PMID- 29366641
TI  - Subcutaneous Fat Distribution is a Prognostic Biomarker for Men with Castration
      Resistant Prostate Cancer.
AB  - PURPOSE: The relationship between body fat distribution and survival remains
      unclear in patients with castration resistant prostate cancer treated with
      docetaxel and androgen receptor axis targeted agents. We investigated whether
      body composition parameters could predict radiographic progression-free and
      cancer specific survival in patients with castration resistant prostate cancer.
      MATERIALS AND METHODS: In this multicenter retrospective study we evaluated data
      on 282 consecutive patients diagnosed with castration resistant prostate cancer
      between September 2009 and March 2017. The subcutaneous fat index, the visceral
      fat index and the skeletal muscle index at the diagnosis of castration resistant
      prostate cancer were determined by computerized tomography data. Survival
      analyses were performed using the subcutaneous fat, visceral fat and skeletal
      muscle indexes dichotomized at 39.9, 58 and 52.4 cm2/m2, respectively. RESULTS:
      At the diagnosis of castration resistant prostate cancer, cancer specific
      survival was independently predicted using prostate specific antigen levels,
      Gleason score 8 or greater, performance status, a shorter interval from androgen
      deprivation therapy to castration resistant prostate cancer and a subcutaneous
      fat index of less than 39.9 cm2/m2. During the median followup of 16.0 months
      patients with a subcutaneous fat index of 39.9 cm2/m2 or greater received more
      docetaxel cycles than patients with a subcutaneous fat index of less than 39.9
      cm2/m2. Compared to patients with a subcutaneous fat index of less than 39.9
      cm2/m2 those with an index of 39.9 cm2/m2 or greater had better 1-year
      progression-free and 2-year cancer specific survival (p = 0.009 and 0.021,
      respectively). CONCLUSIONS: Patients with a subcutaneous fat index of 39.9 cm2/m2
      or greater at the diagnosis of castration resistant prostate cancer showed higher
      progression-free and cancer specific survival rates than those with a
      subcutaneous fat index of less 39.9 cm2/m2 at diagnosis. The subcutaneous fat
      index determined by computerized tomography data could serve as a useful
      objective prognostic factor to discuss patient therapeutic options. Further
      studies are needed to define the roles of each body composition parameter in
      relation to pharmacokinetics and oncologic outcome.

PMID- 29366642
TI  - Multi-institutional Outcomes for Simultaneous and Staged Urinary and Fecal
      Diversions in Patients Without Cancer.
AB  - OBJECTIVE: To compare the morbidity and postoperative recovery between patients
      treated with urinary diversion after colostomy with patients undergoing
      simultaneous double diversion (DD). METHODS: A multi-institutional retrospective
      review was performed in patients treated with urinary diversion after colostomy
      or simultaneous DD between 2007 and 2014 for noncancerous indications. The
      Clavien-Dindo system was used to classify complications occurring within 90 days
      of surgery, and high-grade adverse events (HGAE) were classified grade 3 or
      higher. RESULTS: A total of 46 patients were identified with fecal and urinary
      diversions (19 in the after colostomy (AC) group, 27 in the DD group). Common
      indications for urinary diversion were neurogenic bladder (54%) and urinary
      fistula (44%). Mean hospital stay and return of bowel function after surgery for
      entire cohort was 13 and 7 days, respectively, with no differences between AC and
      DD groups. Almost 50% of patients in the cohort experienced an HGAE but there was
      no difference in HGAE incidence (8/19 AC, 13/27 DD; P = .69) or complication type
      between the groups. Increased operative time (5% risk per every 15 minutes over 7
      hours, P = .03) was the only independent variable associated with increased risk
      of HGAE. DD was not independently associated with increased risk of HGAE compared
      with staged urinary diversion. CONCLUSION: Morbidity and postoperative recovery
      appeared similar whether urinary diversion is performed after colostomy or during
      a DD.

PMID- 29366643
TI  - A Dynamic Structure of Social Trait Space.
AB  - Facial appearance evokes robust impressions of other people's personality traits.
      Recent research suggests that the trait space arising from face-based impressions
      shifts due to context and social cognitive factors. We suggest a novel framework
      in which multiple bottom-up and top-down processes mutually determine a dynamic
      rather than fixed trait space.

PMID- 29366644
TI  - What does power Doppler signal indicate in rheumatoid synovitis? A point of view
      from synovial histopathology.
AB  - To clarify the nature of power Doppler (PD) signals in rheumatoid synovium and to
      establish the connection between PD signals and active inflammation using
      synovial histopathology. Ten adult patients (median age 57.0 years, 9 women and
      one man) with rheumatoid arthritis (RA) were enrolled and received ultrasound
      (US) examinations. US-guided synovial biopsies using core needle were performed
      in 7 knees, 2 wrists and one elbow. Each patient had one joint biopsied. In
      total, 11 synovial specimens were obtained for hematoxylin and eosin staining and
      histopathologic examinations. The US examinations revealed prominent synovial
      hypertrophy in all biopsied joints. Six synovial specimens were PD-positive (from
      3 knees, 2 wrists and 1 elbow) while 5 synovial specimens were PD-negative (from
      5 knees). In comparison with the PD-negative synovial specimens, the PD-positive
      synovial specimens had significantly more lymphocyte infiltration, vessel
      proliferation and lining hyperplasia on histologic examination. There was no
      significant difference in fibrin exudate and stromal fibrosis between the PD
      positive and the PD-negative synovial specimens. PD signals in rheumatoid
      synovium indicate active inflammation and vascularization supported by synovial
      histopathology. Our study establishes the connection between synovial PD signals
      and active synovitis in RA.

PMID- 29366645
TI  - Serum nerve growth factor beta, brain- and glial-derived neurotrophic factor
      levels and psychopathology in unmedicated patients with schizophrenia.
AB  - BACKGROUND: There is accumulating evidence that neurotrophic factors may be
      involved in the pathophysiology of patients with schizophrenia. This study aimed
      to explore the relationship between serum nerve growth factor beta (NGF-beta),
      brain-derived neurotrophic factor (BDNF), and glial-derived neurotrophic factor
      (GDNF) levels and psychopathology in unmedicated patients with schizophrenia.
      METHODS: Serum NGF-beta, BDNF, and GDNF levels were determined using enzyme
      linked-immunosorbent assay (ELISA) in the serum of 30 unmedicated patients with
      schizophrenia. Symptomatology was assessed with the expanded version of the 24
      items brief psychiatric rating scale (BPRS-E), which was divided into four
      conceptual domains: manic excitement/disorganization, depression/anxiety,
      negative symptoms, and positive symptoms. Kolmogorov-Smirnov one sample test was
      performed to test non-parametric variables. Spearman's correlation was performed
      to examine the correlations between the cytokines of interest and
      psychopathology. Benjamini-Hochberg procedure was applied for multiple
      corrections. RESULTS: Serum GDNF levels correlated negatively with the BPRS-total
      (r = -0.533, corrected p = 0.002) and BPRS-manic (r = -0.456, corrected p =
      0.011) subtests. BDNF levels showed a positive correlation with BPRS-total (r =
      0.480, corrected p = 0.007). In addition, NGF-beta did not associate with
      psychopathology measured by BPRS scores. CONCLUSION: Neurotrophic factors play a
      vital role in the regulation of neuroplasticity and neurogenesis in humans. This
      study suggests that BDNF and GDNF may be contributing to the pathological
      mechanisms involved in unmedicated patients with schizophrenia.

PMID- 29366646
TI  - Identification of novel plasminogen activator inhibitor-1 inhibitors with
      improved oral bioavailability: Structure optimization of N-acylanthranilic acid
      derivatives.
AB  - Novel plasminogen activator inhibitor-1 (PAI-1) inhibitors with highly improved
      oral bioavailability were discovered by structure-activity relationship studies
      on N-acyl-5-chloroanthranilic acid derivatives. Because lipophilic N-acyl groups
      seemed to be important for the anthranilic acid derivatives to strongly inhibit
      PAI-1, synthesis of compounds in which 5-chloroanthranilic acid was bound to a
      variety of highly lipophilic moieties with appropriate linkers was investigated.
      As the result it appeared that some of the derivatives possessing aryl- or
      heteroaryl-substituted phenyl groups in the acyl chain had potent in vitro PAI-1
      inhibitory activity. Oral absorbability of typical compounds was also evaluated
      in rats, and compounds 40, 55, 60 and 76 which have diverse chemical structure
      with each other were selected for further pharmacological evaluation.

PMID- 29366647
TI  - Discovery of a novel potent GPR40 full agonist.
AB  - Compound 12 is a GPR40 agonist that realizes the full magnitude of efficacy
      possible via GPR40 receptor agonism. In vitro and in vivo studies demonstrated
      superior glucose lowering by 12 compared to fasiglifam (TAK-875), in a glucose
      dependent manner. The enhanced efficacy observed with the full agonist 12 was
      associated with both direct and indirect stimulation of insulin secretion.

PMID- 29366649
TI  - A multifaceted approach to identify non-specific enzyme inhibition: Application
      to Mycobacterium tuberculosis shikimate kinase.
AB  - Single dose high-throughput screening (HTS) followed by dose-response evaluations
      is a common strategy for the identification of initial hits for further
      development. Early identification and exclusion of false positives is a cost
      saving and essential step in early drug discovery. One of the mechanisms of false
      positive compounds is the formation of aggregates in assays. This study evaluates
      the mechanism(s) of inhibition of a set of 14 compounds identified previously as
      actives in Mycobacterium tuberculosis (Mt) cell culture screening and in vitro
      actives in Mt shikimate kinase (MtSK) assay. Aggregation of hit compounds was
      characterized using multiple experimental methods, LC-MS, 1HNMR, dynamic light
      scattering (DLS), transmission electron microscopy (TEM), and visual inspection
      after centrifugation for orthogonal confirmation. Our results suggest that the
      investigated compounds containing oxadiazole-amide and aminobenzothiazole
      moieties are false positive hits and non-specific inhibitors of MtSK through
      aggregate formation.

PMID- 29366648
TI  - Identification and optimization of soluble epoxide hydrolase inhibitors with dual
      potency towards fatty acid amide hydrolase.
AB  - Multi-target inhibitors have become increasing popular as a means to leverage the
      advantages of poly-pharmacology while simplifying drug delivery. Here, we
      describe dual inhibitors for soluble epoxide hydrolase (sEH) and fatty acid amide
      hydrolase (FAAH), two targets known to synergize when treating inflammatory and
      neuropathic pain. The structure activity relationship (SAR) study described
      herein initially started with t-TUCB (trans-4-[4-(3-trifluoromethoxyphenyl-l
      ureido)-cyclohexyloxy]-benzoic acid), a potent sEH inhibitor that was previously
      shown to weakly inhibit FAAH. Inhibitors with a 6-fold increase of FAAH potency
      while maintaining high sEH potency were developed by optimization. Interestingly,
      compared to most FAAH inhibitors that inhibit through time-dependent covalent
      modification, t-TUCB and related compounds appear to inhibit FAAH through a time
      independent, competitive mechanism. These inhibitors are selective for FAAH over
      other serine hydrolases. In addition, FAAH inhibition by t-TUCB appears to be
      higher in human FAAH over other species; however, the new dual sEH/FAAH
      inhibitors have improved cross-species potency. These dual inhibitors may be
      useful for future studies in understanding the therapeutic application of dual
      sEH/FAAH inhibition.

PMID- 29366651
TI  - Degradation of huntingtin mediated by a hybrid molecule composed of IAP
      antagonist linked to phenyldiazenyl benzothiazole derivative.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by aggregation of mutant huntingtin (mHtt), and removal of mHtt is
      expected as a potential therapeutic option. We previously reported protein
      knockdown of Htt by using hybrid small molecules (Htt degraders) consisting of
      BE04, a ligand of ubiquitin ligase (E3), linked to probes for protein aggregates.
      Here, in order to examine the effect of changing the ligand, we synthesized a
      similar Htt degrader utilizing MV1, an antagonist of the inhibitor of apoptosis
      protein (IAP) family (a subgroup of ubiquitin E3 ligases), which is expected to
      have a higher affinity and specificity for IAP, as compared with BE04. The MV1
      based hybrid successfully induced interaction between Htt aggregates and IAP, and
      reduced mHtt levels in living cells. Its mode of action was confirmed to be the
      same as that of the BE04-based hybrid. However, although the affinity of MV1 for
      IAP is greater than that of BE04, the efficacy of Htt degradation by the MV1
      based molecule was lower, suggesting that linker length between the ligand and
      probe might be an important determinant of efficacy.

PMID- 29366650
TI  - Triptolide derivatives as potential multifunctional anti-Alzheimer agents:
      Synthesis and structure-activity relationship studies.
AB  - Owning to the promising neuroprotective profile and the ability to cross the
      blood-brain barrier, triptolide has attracted extensive attention. Although its
      limited solubility and toxicity have greatly hindered clinical translation,
      triptolide has nonetheless emerged as a promising candidate for structure
      activity relationship studies for Alzheimer's disease. In the present study, a
      series of triptolide analogs were designed and synthesized, and their
      neuroprotective and anti-neuroinflammatory effects were then tested using a cell
      culture model. Among the triptolide derivatives tested, a memantine conjugate,
      compound 8, showed a remarkable neuroprotective effect against Abeta1-42 toxicity
      in primary cortical neuron cultures as well as an inhibitory effect against LPS
      induced TNF-alpha production in BV2 cells at a subnanomolar concentration. Our
      findings provide insight into the different pharmacophores that are responsible
      for the multifunctional effects of triptolide in the central nervous system. Our
      study should help in the development of triptolide-based multifunctional anti
      Alzheimer drugs.

PMID- 29366652
TI  - Synthesis and evaluation of radiolabeled AGI-5198 analogues as candidate
      radiotracers for imaging mutant IDH1 expression in tumors.
AB  - Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are commonly
      found in gliomas. AGI-5198, a potent and selective inhibitor of the mutant IDH1
      enzyme, was radiolabeled with radioiodine and fluorine-18. These radiotracers
      were evaluated as potential probes for imaging mutant IDH1 expression in tumors
      with positron emission tomography (PET). Radioiodination of AGI-5198 was achieved
      using a tin precursor in 79 +/- 6% yield (n = 9), and 18F-labeling was
      accomplished by the Ugi reaction in a decay-corrected radiochemical yield of 2.6
      +/- 1.6% (n = 5). The inhibitory potency of the analogous nonradioactive
      compounds against mutant IDH1 (IDH1-R132H) was determined in enzymatic assays.
      Cell uptake studies using radiolabeled AGI-5198 analogues revealed somewhat
      higher uptake in IDH1-mutated cells than that in wild-type IDH1 cells. The
      radiolabeled compounds displayed favorable tissue distribution characteristics in
      vivo, and good initial uptake in IDH1-mutated tumor xenografts; however, tumor
      uptake decreased with time. Radioiodinated AGI-5198 exhibited higher tumor-to
      background ratios compared with 18F-labeled AGI-5198; unfortunately, similar
      results were observed in wild-type IDH1 tumor xenografts as well, indicating lack
      of selectivity for mutant IDH1 for this tracer. These results suggest that AGI
      5198 analogues are not a promising platform for radiotracer development.
      Nonetheless, insights gained from this study may help in design and optimization
      of novel chemical scaffolds for developing radiotracers for imaging the mutant
      IDH1 enzyme.

PMID- 29366654
TI  - Design and validation of a tool for the evaluation of the quality of
      Cardiopulmonary Resuscitation: SIEVCA-CPR 2.0(r).
AB  - INTRODUCTION: Currently, no system completely evaluates the quality of cardio
      pulmonary resusciation. METHODS: A cross-sectional, prospective, longitudinal
      study using Delphi methodology was performed in three phases: preparatory,
      consultation and consensus. The validation was made by a prospective longitudinal
      study using the tool in the evaluation of 11 videos to determine the intra-class
      correlation coefficient (ICC) and the intra-subject (ICC-Initial), the latter
      repeated at four weeks (ICC-Final). We have determined intra-subject ICC: Initial
      Final. This last result has been compared with a gold-standard value. RESULTS:
      After the first phase, a 28-items list has been developed. In the second phase:
      ICC-Initial = 0.727 (p < .001), 95% CI (0.625, 0.801), ICC-Final = 0.860 (p <
      .001), 95% CI (0.807; 0.898) and ICC Initial-Final = 0.880 (p < .001), 95% CI
      (0.835; 0.913). Finally, an online tool has been developed (SIEVCA 2.0).
      CONCLUSION: The designed tool presents good reliability in the assessment of
      cardio pulmonary resuscitation and it is useful in different fields and
      scenarios.

PMID- 29366653
TI  - Discovery of selective 2,4-diaminoquinazoline toll-like receptor 7 (TLR 7)
      agonists.
AB  - The discovery of a novel series of highly potent quinazoline TLR 7/8 agonists is
      described. The synthesis and structure-activity relationship is presented.
      Structural requirements and optimization of this series toward TLR 7 selectivity
      afforded the potent agonist 48. Pharmacokinetic and pharmacodynamic studies
      highlighted 48 as an orally available endogenous interferon (IFN-alpha) inducer
      in mice.

PMID- 29366655
TI  - An automated method for choroidal thickness measurement from Enhanced Depth
      Imaging Optical Coherence Tomography images.
AB  - The choroid is vascular tissue located underneath the retina and supplies oxygen
      to the outer retina; any damage to this tissue can be a precursor to retinal
      diseases. This paper presents an automated method of choroidal segmentation from
      Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) images. The
      Dijkstra shortest path algorithm is used to segment the choroid-sclera interface
      (CSI), the outermost border of the choroid. A novel intensity-normalisation
      technique that is based on the depth of the choroid is used to equalise the
      intensity of all non-vessel pixels in the choroid region. The outer boundary of
      choroidal vessel and CSI are determined approximately and incorporated to the
      edge weight of the CSI segmentation to choose optimal edge weights. This method
      is tested on 190 B-scans of 10 subjects against choroid thickness (CTh) results
      produced manually by two graders. For comparison, results obtained by two state
      of-the-art automated methods and our proposed method are compared against the
      manual grading, and our proposed method performed the best. The mean root-mean
      square error (RMSE) for finding the CSI boundary by our method is 7.71+/-6.29
      pixels, which is significantly lower than the RMSE for the two other state-of-the
      art methods (36.17+/-11.97 pixels and 44.19+/-19.51 pixels). The correlation
      coefficient for our method is 0.76, and 0.51 and 0.66 for the other two state-of
      the-art methods. The interclass correlation coefficients are 0.72, 0.43 and 0.56
      respectively. Our method is highly accurate, robust, reliable and consistent.
      This identification can enable to quantify the biomarkers of the choroidin large
      scale study for assessing, monitoring disease progression as well as early
      detection of retinal diseases. Identification of the boundary can help to
      determine the loss or change of choroid, which can be used as features for the
      automatic determination of the stages of retinal diseases.

PMID- 29366656
TI  - Food and feed safety of DAS-444O6-6 herbicide-tolerant soybean.
AB  - DAS-444O6-6 soybean was genetically engineered (GE) to withstand applications of
      three different herbicides. Tolerance to glufosinate and glyphosate is achieved
      through expression of the phosphinothricin acetyltransferase (PAT) and double
      mutated maize 5-enolpyruvyl shikimate-3-phosphate synthase (2mEPSPS) enzymes,
      respectively. These proteins are expressed in currently commercialized crops and
      represent no novel risk. Tolerance to 2,4-dichlorophenoxyacetic acid (2,4-D) is
      achieved through expression of the aryloxyalkanoate dioxygenase 12 (AAD-12)
      enzyme, which is novel in crops. The safety of the AAD-12 protein and DAS-444O6-6
      event was assessed for food and feed safety based on the weight of evidence and
      found to be as safe as non-GE soybean.

PMID- 29366657
TI  - The cost of observation care for commercially insured patients visiting the
      emergency department.
AB  - OBJECTIVE: To examine trends in the use of ED observation stays among a national
      sample of patients with commercial insurance, and assess the patient cost-burden
      of an observation stay relative to an short inpatient hospitalization from the
      ED. METHODS: Retrospective analysis of ED observation stays and inpatient
      hospitalizations from 2008 to 2015 using the Truven MarketScan(r) Commercial
      Claims and Encounters database. Index ED visits were identified from claims files
      and assessed for evidence of an observation or inpatient hospitalization. Total
      and out-of-pocket costs were calculated for the index hospitalization and a 30
      day episode of care and standardized to 2015 $USD. Costs for ED patients with an
      observation stay were compared to a similar, propensity-matched cohort of ED
      patients hospitalized as inpatients. RESULTS: Over the 8 year period, observation
      stay admissions increased from 4.3% to 6.8% of total ED visits (60.5% relative
      increase) while inpatient admissions fell from 10.8% to 8.9% (16.6% relative
      decrease). In 2015, the mean total cost was $8162 for an observation stay and
      $22,865 for an inpatient hospitalization. Patient out-of-pocket costs were $962
      and $1403, respectively. Among the propensity-matched cohorts, relative mean
      costs for the index hospitalization were 41% higher and patient out-of-pocket
      costs were 33% higher if the patient was admitted as an inpatient from the ED
      versus observation during their hospitalization. CONCLUSIONS: Observation
      hospitalizations are an increasingly common disposition for patients entering the
      hospital through the ED. Both total and patient out-of-pocket costs are lower, on
      average, for an observation stay compared with a similar inpatient admission for
      ED patients requiring hospitalization.

PMID- 29366658
TI  - Integration of lung ultrasound in the diagnostic reasoning in acute dyspneic
      patients: A prospective randomized study.
AB  - INTRODUCTION: Misdiagnosis in acute dyspneic patients (ADP) has consequences on
      their outcome. Lung ultrasound (LUS) is an accurate tool to improve diagnostic
      performance. The main goal of this study was to assess the determinants of
      increased diagnostic accuracy using LUS. MATERIALS: Multicentre, prospective,
      randomized study including emergency physicians and critical care physicians
      treating ADP on a daily basis. Each participant received three difficult clinical
      cases of ADP: one with only clinical data (OCD), one with only LUS data (OLD),
      and one with both. Ultrasound video loops of A, B and C profiles were associated
      with the cases. Which physician received what data for which clinical case was
      randomized. Physicians assessed the diagnostic probability from 0 to 10 for each
      possible diagnosis. The number of uncertain diagnoses (NUD) was the number of
      diagnoses with a diagnostic probability between 3 and 7, inclusive. RESULTS:
      Seventy-six physicians responded to the study cases (228 clinical cases
      resolved). Among the respondents, 28 (37%) were female, 64 (84%) were EPs, and
      the mean age was 37+/-8 years. The mean NUDs, respectively, when physicians had
      OCD, OLD, and both were 2.9+/-1.8, 2.2+/-1.7, 2.2+/-1.8 (p = 0.02). Ultrasound
      data and ultrasound frequency of use were the only variables related to the NUD.
      Higher frequency of ultrasound use by physicians decreased the number of
      uncertain diagnoses in difficult clinical cases with ultrasound data (OLD or
      associated with clinical data). CONCLUSION: LUS decreases the NUD in ADP. The
      ultrasound frequency of use decreased the NUD in ADP clinical cases with LUS
      data.

PMID- 29366659
TI  - Predictability of successful trans-arterial embolization in pelvic fracture
      bleeding based on patient initial presentation.
AB  - BACKGROUND: Pelvic fracture bleeding generally leads to hemorrhagic shock. Trans
      arterial embolization (TAE) is regarded as the most useful treatment; however,
      the initial presentation of the patient can impact the effectiveness of TAE for
      pelvic fracture bleeding. The aim of this retrospective study is to explore
      whether the patient data at the initial presentation can predict the success of
      TAE for pelvic fracture bleeding. METHODS: Twenty-seven charts were
      retrospectively reviewed. TAE failure was defined as any patient who eventually
      received an exigent laparotomy or who died due to uncontrolled bleeding after
      TAE. For patients who received TAE, we analyzed factors recorded at the initial
      presentation, including age, gender, systolic blood pressure, heart rate,
      respiratory rate, body temperature, Glasgow coma scale (GCS) score, injury
      severity score (ISS) and associated injuries, using Pearson's correlation and
      independent t-tests. The odds ratio was used to determine the cut-off values for
      the patient presentation findings related to successful TAE and thus was used to
      assess congruity. RESULTS: Successful TAE was not correlated with age or gender.
      The hierarchical order of statistically significant associations between
      successful TAE and initial presentation data was as follows: the patient's body
      temperature, associated injury, respiratory rate, systolic blood pressure, GCS
      score, and ISS. The odds ratios for all statistically significant initial
      presentation factors were within a 95% confidence interval. CONCLUSION: The
      findings upon initial presentation of a patient with pelvic fracture bleeding
      that were related to the predictability of successful TAE include the following:
      hypothermia prevention with maintenance of the body temperature above 36 degrees
      C, associated injuries limited to two organ systems, maintenance of the
      respiratory rate at approximately twenty-two breaths per minute, a sustained
      systolic blood pressure of approximately 90mmHg, maintenance of a heart rate of
      approximately one hundred beats per minute, a minor head injury with a GCS score
      greater than thirteen and a moderate ISS of less than twenty.

PMID- 29366660
TI  - Metal phosphide ingestions: How the hospital became a HAZMAT incident.

PMID- 29366661
TI  - Long-Term Results of Hemiarthroplasty Compared With Arthrodesis for
      Osteoarthritis of the First Metatarsophalangeal Joint.
AB  - If operative treatment is opted for grade 3 and 4 osteoarthritis of the first
      metatarsophalangeal joint, arthrodesis is considered the standard of care.
      However, if preservation of joint mobility is preferred, implant arthroplasty
      could be favored. Previous studies have suggested hemiarthroplasty might result
      in less pain, better function, and greater patient satisfaction compared with
      arthrodesis. However, these studies only evaluated short-term results (range 2.2
      to 6.6 years). The aim of our study was to determine whether patients treated
      with hemiarthroplasty would show better postoperative outcomes compared with
      those treated with arthrodesis after >=5 years after surgery. The American
      Orthopaedic Foot and Ankle Society hallux metatarsophalangeal interphalangeal
      (AOFAS-HMI) scale score was used as the primary outcome measure. Secondary
      outcomes addressed satisfaction rates, patient procedure recommendation, and
      number of unplanned repeat surgical procedures. We also addressed the influence
      of the procedures on daily activities (work and sports), the influence of smoking
      on the postoperative results, and the costs for both procedures. A total of 47
      primary arthrodeses and 31 hemiarthroplasties performed between January 2005 and
      December 2011 were evaluated. After a mean follow-up period of 8.3 (range 5 to
      11.8) years, the mean AOFAS-HMI scale score after arthrodesis and
      hemiarthroplasty was 72.8 +/- 14.5 and 89.7 +/- 6.6, respectively (p = .001). The
      patients were significantly more pleased after hemiarthroplasty (p < .001), and
      this procedure was recommended more often (p < .001). The number of unplanned
      repeat surgical procedures did not differ between the 2 groups. Patients resumed
      sports activities significantly sooner after hemiarthroplasty (p = .002). The
      overall crude costs were similar for both procedures. Our results have shown more
      favorable postoperative outcomes for hemiarthroplasty compared with arthrodesis
      as operative treatment of osteoarthritis of the first metatarsophalangeal joint
      after a mean follow-up period of 8.3 years.

PMID- 29366662
TI  - CD45 in human physiology and clinical medicine.
AB  - CD45 is an evolutionary highly conserved receptor protein tyrosine phosphatase
      exclusively expressed on all nucleated cells of the hematopoietic system. It is
      characterized by the expression of several isoforms, specific to a certain cell
      type and the developmental or activation status of the cell. CD45 is one of the
      key players in the initiation of T cell receptor signaling by controlling the
      activation of the Src family protein-tyrosine kinases Lck and Fyn. CD45
      deficiency results in T- and B-lymphocyte dysfunction in the form of severe
      combined immune deficiency. It also plays a significant role in autoimmune
      diseases and cancer as well as in infectious diseases including fungal
      infections. The knowledge collected on CD45 biology is rather vast, but it
      remains unclear whether all findings in rodent immune cells also apply to human
      CD45. This review focuses on human CD45 expression and function and provides an
      overview on its ligands and role in human pathology.

PMID- 29366663
TI  - Soluble PD-L1 with PD-1-binding capacity exists in the plasma of patients with
      non-small cell lung cancer.
AB  - PD-L1 is one of the important immune checkpoint molecules that can be targeted by
      cancer immunotherapies. PD-L1 has a soluble form (sPD-L1) and a membrane-bound
      form (mPD-L1). Conventional enzyme-linked immunosorbent assay (ELISA) systems can
      detect sPD-L1 using anti-PD-L1 capture antibody through the antigen-antibody
      reaction, but cannot evaluate the quality and function of sPD-L1. In this study,
      we developed a novel ELISA system for the detection and quantification of sPD-L1
      with PD-1-binding capacity (bsPD-L1). To capture bsPD-L1 through the ligand
      receptor reaction, the anti-PD-L1 capture antibody in the conventional ELISA was
      replaced with PD-1-Ig fusion protein in the new ELISA. The new ELISA could detect
      bsPD-L1 in 29 out of 75 plasma samples from patients with non-small cell lung
      cancer (NSCLC), with higher sensitivity and frequency than the conventional
      ELISA. The western blot analysis showed that sPD-L1 in the plasma was
      glycosylated. Treatment of the samples with glycosidase reduced the absorbance
      determined by the new ELISA but had no effect on the absorbance determined by the
      conventional ELISA. These results suggest that glycosylation of sPD-L1 is
      important for its binding to the immobilized PD-1 in the new ELISA. Our new ELISA
      system may be useful for the evaluation of functional sPD-L1 with PD-1-binding
      capacity in cancer patients.

PMID- 29366664
TI  - Brain disposition, metabolism and behavioral effects of the synthetic opioid AH
      7921 in rats.
AB  - 3,4-Dichloro-N-benzamide (AH-7921) is a cyclohexyl-methylbenzamide derivative
      with analgesic activity, whose abuse was associated with several fatal
      intoxications, included in Schedule I of UN Single Convention on Narcotic Drugs.
      We validated an HPLC-MS/MS method to investigate its brain disposition and
      metabolism after single and repeated injections; in parallel, we evaluated its
      central behavioral effects. After an intraperitoneal injection of 10 mg/kg, the
      analgesic effect appeared after 5 min and persisted up to 4 h; brain absorption
      was rapid (tmax 30 min) and large (brain-to-plasma ratio 16), with active
      concentration >700 ng/g. By high-resolution MS we identified several metabolites
      in plasma and brain, the most important being N-demethylated and N,N
      didemethylated metabolites; they showed high brain permeability, although they
      probably do not contribute to the analgesic effect of the parent compound (brain
      tmax>2 h). Starting 2 h after treatment, the two metabolites showed higher plasma
      and brain concentrations than the parent molecule, which persisted much longer,
      and could be used to evaluate drug intake in human consumers. Tolerance was
      observed after seven daily doses, when the compound's analgesic effect was 14%
      lower than after the first dose; since brain concentrations did not decrease in
      parallel, the development of pharmacodynamic tolerance can be suggested. However,
      pharmacokinetic tolerance is also likely, as brought to light by the data after a
      dose challenge, given after a 48 h washout period from the 7th dose, showing a
      lower brain-to-plasma ratio. We also describe the rewarding effect of AH-7921
      (conditioned place preference), suggesting a high risk of addiction in humans.

PMID- 29366666
TI  - Depression and anxiety in caregivers of patients with celiac disease. Author's
      reply.

PMID- 29366665
TI  - The outcome of secondary resurfacing of the patella following total knee
      arthroplasty: Results from the Trent and Wales Arthroplasty Register.
AB  - BACKGROUND: We sought to determine whether patients undergoing secondary patella
      resurfacing (SPR) benefited from the procedure by assessing postoperative
      satisfaction via a postal questionnaire. METHODS: All such patients included in
      the Trent and Wales Arthroplasty Register were invited to participate using
      patient-reported outcome measures (PROMs). We identified 223 patients who had
      undergone SPR over a 20-year period. Forty-two had died according to death
      register checks. Eighty-eight of 181 (48.6%) questionnaires were completed. The
      mean age at resurfacing was 67 (min. 42, max. 81); 52% were female. The median
      time to follow-up was 55months (interquartile range (IQR) 41-111). Median time to
      SPR was 28months (IQR 20-42). RESULTS: Thirty-nine patients (44%) felt that SPR
      resolved the problem of pain in the front of their knee. All PROMs were
      significantly better for those who felt that the resurfacing had worked (Oxford
      Knee Score 29 vs. 16, P<0.05, modified Kujala 51 vs. 32, P<0.05, EQ5D-3L 0.616
      vs. 0.384, P<0.05). Based on PROMs, SPR produces a satisfactory outcome in two of
      every five patients. CONCLUSIONS: Surgeons must be clear on the cause of anterior
      knee pain post-total knee replacement, and patients must be made aware of what
      outcomes can be reasonably expected from this procedure.

PMID- 29366668
TI  - The influence of learning environment on trainee pharmacy technicians' education
      and training experiences.
AB  - BACKGROUND: In Great Britain (GB), pharmacy technicians (PTs) are registered
      professionals, with their education and training regulated; little is known about
      this or the learning environment in which it takes place. OBJECTIVES: This study
      aimed to profile recently registered pre-registration trainee pharmacy
      technicians (PTPTs) in GB and capture views on PTPTs' training experiences,
      focussing on differences in community and hospital settings. METHODS: A mixed
      methods study was conducted in 2013-14, following university ethics approval. One
      to-one, semi-structured telephone interviews with face-to-face and distance
      education providers, and hospital and community pharmacy employers of PTPTs
      explored views on education delivery, work-based learning, and assessment.
      Interviews were transcribed verbatim, analysed thematically and findings informed
      design of a census survey of all 1457 recently registered PTs, investigating
      satisfaction with various aspects of their training. Quantitative data were
      analysed using SPSS v20, employing comparative statistics (Mann-Whitney U, Chi
      Square). RESULTS: Six-hundred and forty-six questionnaires were returned
      (response rate 44.3%), 632 were usable. Three-quarters (75.9%) of respondents had
      trained in community; the majority (88.0%) were female, the average age was 35.26
      +/- 10.22. Those based in hospitals were more satisfied with their training:
      hospital trainees worked in larger teams and tended to be better supported, they
      had more study time, and were more likely to complete their training in the
      intended two-year period. Interviews with staff in 17 Further Education colleges,
      6 distance providers, 16 community pharmacies and 15 NHS organisations confirmed
      survey findings and offered explanations into why differences in training
      experiences may exist. CONCLUSIONS: This study has identified differences between
      PTPTs' work-based experiences in hospital and community pharmacy. Perceiving
      PTPTs as 'apprentices' vs. 'employees' may define how their training is managed
      by employers. Clarity in PTs' roles, responsibilities, and expected competencies
      upon registration can ensure training is structured and delivered in a suitable
      and equitable manner across sectors.

PMID- 29366667
TI  - Anatomical characterization of the brachial plexus in dog cadavers and comparison
      of three blind techniques for blockade.
AB  - OBJECTIVES: To describe the ventral spinal nerve rami contribution to the
      formation of the brachial plexus (BP), and to compare ease of performing and
      nerve staining between three blind techniques for BP blockade in dogs. STUDY
      DESIGN: Prospective, randomized, blind study. ANIMALS: A total of 18 dog cadavers
      weighing 28.2 +/- 9.7 kg (mean +/- standard deviation). METHODS: Dogs were
      randomly assigned to two of three BP treatments: traditional approach (TA),
      perpendicular approach (PA), and axillary approach (AA). Dye (0.2 mL kg-1) was
      injected in the left BP using a spinal needle; another BP treatment was used in
      the right BP. Landmarks (L) included: L1, midpoint between point of the shoulder
      and sixth cervical (C6) transverse process; L2, scapulohumeral joint; and L3,
      first rib. For TA, the needle was introduced craniocaudally through L1, medial to
      the limb and cranial to L3. For PA, the needle was directed perpendicular and
      caudal to L2, aligned with L1, until cranial to L3. For AA, the needle was
      directed ventrodorsally, parallel and cranial to L3 until at L1. All BPs were
      scored for dyeing quality [0 (poor) to 5 (excellent)]. The left BP was dissected
      for nerve origins. Durbin test was used to compare scores (p < 0.05). RESULTS: In
      all dogs, the musculocutaneous nerve originated from C7 and C8; the radial nerve
      from C8, the first thoracic vertebra (T1) (16/18 dogs) and C7 (2/18); and the
      median and ulnar nerves from C8, T1 (17/18) and C7 (1/18). Respective raw scores
      and adjusted scores for the incomplete block design were not significantly
      different (p = 0.72; ranks TA 16.5, PA 19.0, AA 18.5). CONCLUSIONS AND CLINICAL
      RELEVANCE: The musculocutaneous, median, ulnar and radial nerves originate from
      C7, C8 and T1. Regardless of the technique, knowledge of anatomy and precise
      landmarks are relevant for correct dye dispersion.

PMID- 29366669
TI  - Reliability and validity of SF-12v2 among adults with self-reported cancer.
AB  - BACKGROUND: The SF-12v2 has been validated in general population and other
      conditions but the evidence is limited in Americans with cancer. OBJECTIVE: To
      assess reliability and validity of SF-12v2 among adults with self-reported cancer
      using the Medical Expenditure Panel Survey (MEPS). METHODS: Self-reported cancer
      participants (SCPs) were identified from 2003 MEPS. SF-12v2 was administered as
      part of self-administered questionnaires. Physical (PCS12) and mental (MCS12)
      component scores of SF-12v2 were evaluated for reliability (internal consistency,
      test-retest) and validity (convergent, discriminant, predictive, concurrent).
      RESULTS: 420 SCPs were identified with average age of 59.3 years (SE = 0.9).
      10.7% had multiple cancers (>1) and 52% had at least one other chronic condition
      (OCC). Average PCS12 and MCS12 were 45.09 (SE = 0.5) and 50.75 (SE = 0.5). PCS12
      and MCS12 demonstrated high internal consistency (alphaPCS12 = 0.89; alphaMCS12 =
      0.88), acceptable test-retest reliability (ICCPCS12 = 0.82; ICCMCS12 = 0.73),
      strongly correlated with most of the expected EQ-5D domains (r = 0.51-0.71), and
      demonstrated strong convergent validity on perceived health (r = 0.61) and
      perceived mental health (r = 0.52). PCS12 and MCS12 were able to discriminate
      between groups with and without physical/cognitive limitations. Only PCS12 was
      negatively correlated with number of OCCs. CONCLUSION: The SF-12v2 is a reliable
      and valid instrument to quantify health-related quality of life among adults with
      self-reported cancer.

PMID- 29366670
TI  - Characterization of catalytic and non-catalytic activities of EgGST2-3, a
      heterodimeric glutathione transferase from Echinococcus granulosus.
AB  - Glutathione transferases (GSTs) perform several catalytic and non-catalytic roles
      in the defense against toxicities of electrophile compounds and oxidative stress,
      and therefore are involved in stress-response and cell detoxification.
      Previously, we have provided evidence indicating that EgGST2 and EgGST3, two
      phylogenetically distant Echinococcus granulosus GSTs, can naturally form a
      heterodimeric structure (EgGST2-3). In the present work, the recombinant
      heterodimer GST (rEgGST2-3) is characterized. Hence, rEgGST2-3 was able to
      conjugate GSH to three substrates: 1-chloro-2,4-dinitrobenzene (CDNB, general
      substrate for GSTs), 1,2-dichloro-4-nitrobenzene (specific substrate for
      mammalian Mu class) and trans,trans-deca-2,4-dienal (reactive carbonyl). The
      canonical activity was considerably reduced by all the conventional inhibitors
      (cybacron blue, triphenylthin chloride and bromosulfophthalein) and by other
      inhibitors (ellagic acid, alizarin and chenodeoxycholic acid). Besides this,
      rEgGST2-3 activity was inhibited by a number of anthelmintic drugs, where the
      halogenated phenolic drugs (mainly bithionol and hexachlorophene) acted as
      stronger inhibitors, suggesting they may bind to the EgGST2-3. Moreover, rEgGST2
      3 exhibited glutathione-peroxidase activity, and its specific constant (kcat/KM)
      was calculated. Finally, rEgGST2-3 displayed the ability to bind non-substrate
      molecules, particularly anthelmintic drugs, suggesting that ligandin activity may
      have potential to act as a passive protection parasite mechanism. Overall, the
      rEgGST2-3 behavior was shown to be both complementary and redundant to that
      reported for rEgGST1, another characterized GST from E. granulosus. It would be
      appropriate that different enzymes in the same organism do not have exactly the
      same functional properties to develop a better adaptation to life in the host.

PMID- 29366672
TI  - Resuscitation highlights in 2017.

PMID- 29366671
TI  - Temperature-dependent erosivity of drinks in a model simulating oral fluid
      dynamics.
AB  - OBJECTIVES: Aim of this investigation was to study the temperature-dependent in
      vitro enamel erosion of five acidic drinks and citric acid under controlled
      conditions in an artificial mouth. METHODS: The erosive potential of Orange
      juice, Coca-Cola Zero, Sprite Zero, two fruit teas and citric acid (control) was
      investigated on bovine enamel specimens at temperatures between 5  degrees C and
      55  degrees C. The pH values and total calcium content of all test drinks were
      determined. Specimens were immersed into an artificial mouth to imitate
      physiological oral conditions for 60 h. Cyclic de- and re-mineralization was
      performed, imitating the intake of six drinks in six h followed by a six-hour
      remineralization phase, where only artificial saliva ran over the specimens.
      Total erosive enamel loss was determined by contact profilometry. Differences in
      substance loss at different temperatures were tested for statistical significance
      (p-values <= 0.05) by means of ANOVA. RESULTS: Rising liquid temperature did not
      result in a considerable change of pH. Highest substance loss was observed for
      citric acid (33.6 +/- 6 MUm to 38.7 +/- 6 MUm), while only little erosion was
      induced by fruit tea (0.8 +/- 1 MUm to 5.9 +/- 1 MUm). Rising liquid temperature
      did not result in significantly increased substance loss for citric acid, orange
      juice and Coca-Cola Zero. Sprite Zero and both fruit teas, however, caused
      significantly (p < 0.001) more enamel loss at elevated temperature. CONCLUSIONS:
      Not all investigated drinks showed a temperature-induced change in erosivity.
      CLINICAL SIGNIFICANCE: For some erosive beverages it can be recommended to keep
      the consummation temperature as low as possible to decrease the risk of erosive
      tooth substance loss.

PMID- 29366673
TI  - Serum albumin impedes the amyloid aggregation and hemolysis of human islet
      amyloid polypeptide and alpha synuclein.
AB  - Protein aggregation is a ubiquitous phenomenon underpinning the origins of a
      range of human diseases. The amyloid aggregation of human islet amyloid
      polypeptide (IAPP) and alpha synuclein (alphaS), specifically, is a hallmark of
      type 2 diabetes (T2D) and Parkinson's disease impacting millions of people
      worldwide. Although IAPP and alphaS are strongly associated with pancreatic beta
      cell islets and presynaptic terminals, they have also been found in blood
      circulation and the gut. While extensive biophysical and biochemical studies have
      been focused on IAPP and alphaS interacting with cell membranes or model lipid
      vesicles, the roles of plasma proteins on the amyloidosis and membrane
      association of these two major types of amyloid proteins have rarely been
      examined. Using a thioflavin T kinetic assay, transmission electron microscopy
      and a hemolysis assay here we show that human serum albumin, the most abundant
      protein in the plasma, impeded the fibrillization and mitigated membrane damage
      of both IAPP and alphaS. This study offers a new insight on the native inhibition
      of amyloidosis.

PMID- 29366675
TI  - An atlantoaxial rotatory subluxation secondary to a parapharyngeal abscess.

PMID- 29366676
TI  - Two novel mutations in the BCKDHB gene that cause maple syrup urine disease.
AB  - BACKGROUND: Maple syrup urine disease (MSUD) is a rare metabolic disorder of
      autosomal recessive inheritance caused by decreased activity of branched-chain
      alpha-ketoacid dehydrogenase complex (BCKD). Mutations in the three genes
      (BCKDHA, BCKDHB and DBT) are associated with MSUD. Here, we describe the
      presenting symptoms, clinical course and gene mutation analysis of a Chinese boy
      with MSUD. METHODS: Plasma amino acid analysis was performed by tandem mass
      spectrometry and the levels of organic acids in urine were measured with gas
      chromatography-mass spectrometry. The BCKDHB gene was sequenced by Sanger method.
      Furthermore, the significance of the novel mutations was predicted by Polyphen
      and Mutationtaster. After diagnosis, the patient was fed with protein-restricted
      diet to reduce intake of BCAA and was treated with l-carnitine. Metabolic
      parameters, clinical presentation and mental development were followed up.
      RESULTS: The patient was diagnosed as MSUD. Two novel BCKDHB mutations (c.523 T >
      C and c.478-25_552del100) were identified. In silico analysis predicted that the
      two mutations were "disease causing". The boy tolerated the treatment well and
      had symptomatic improvement. He presented with mild hypotonia and had nearly
      normal DQ scores at the age of 10 months. The two novel mutations resulted in the
      clinical manifestations of MSUD. Our results may reflect the heterogeneity of the
      pathogenic variants found in patients with MSUD.

PMID- 29366674
TI  - Cardiolipin dynamics and binding to conserved residues in the mitochondrial
      ADP/ATP carrier.
AB  - Cardiolipin in eukaryotes is found in the mitochondrial inner membrane, where it
      interacts with membrane proteins and, although not essential, is necessary for
      the optimal activity of a number of proteins. One of them is the mitochondrial
      ADP/ATP carrier, which imports ADP into the mitochondrion and exports ATP. In the
      crystal structures, cardiolipin is bound to three equivalent sites of the ADP/ATP
      carrier, but its role is unresolved. Conservation of residues at these
      cardiolipin binding sites across other members of the mitochondrial carrier
      superfamily indicates cardiolipin binding is likely to be important for the
      function of all mitochondrial carriers. Multiscale simulations were performed in
      a cardiolipin-containing membrane to investigate the dynamics of cardiolipin
      around the yeast and bovine ADP/ATP carriers in a lipid bilayer and the
      properties of the cardiolipin-binding sites. In coarse-grain simulations,
      cardiolipin molecules bound to the carriers for longer periods of time than
      phosphatidylcholine and phosphatidylethanolamine lipids-with timescales in the
      tens of microseconds. Three long-lived cardiolipin binding sites overlapped with
      those in the crystal structures of the carriers. Other shorter-lived cardiolipin
      interaction sites were identified in both membrane leaflets. However, the
      timescales of the interactions were of the same order as phosphatidylcholine and
      phosphatidylethanolamine, suggesting that these sites are not specific for
      cardiolipin binding. The calculation of lipid binding times and the overlap of
      the cardiolipin binding sites between the structures and simulations demonstrate
      the potential of multiscale simulations to investigate the dynamics and behavior
      of lipids interacting with membrane proteins.

PMID- 29366677
TI  - Serum Amyloid A1 Is an Epithelial Prorestitutive Factor.
AB  - Several proteins endogenously produced during the process of intestinal wound
      healing have demonstrated prorestitutive properties. The presence of serum
      amyloid A1 (SAA1), an acute-phase reactant, within inflamed tissues, where it
      exerts chemotaxis of phagocytes, is well recognized; however, a putative role in
      intestinal wound repair has not been described. Herein, we show that SAA1 induces
      intestinal epithelial cell migration, spreading, and attachment through a formyl
      peptide receptor 2-dependent mechanism. Induction of the prorestitutive phenotype
      is concentration and time dependent and is associated with epithelial reactive
      oxygen species production and alterations in p130 Crk-associated substrate
      staining. In addition, using a murine model of wound recovery, we provide
      evidence that SAA1 is dynamically and temporally regulated, and that the
      elaboration of SAA1 within the wound microenvironment correlates with the influx
      of SAA1/CD11b coexpressing immune cells and increases in cytokines known to
      induce SAA expression. Overall, the present work demonstrates an important role
      for SAA in epithelial wound recovery and provides evidence for a physiological
      role in the wound environment.

PMID- 29366678
TI  - Galectin-3 Enhances Avian H5N1 Influenza A Virus-Induced Pulmonary Inflammation
      by Promoting NLRP3 Inflammasome Activation.
AB  - Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute
      respiratory distress syndrome in humans. Virus-induced excessive inflammatory
      response contributes to severe disease and high mortality rates. Galectin-3, a
      beta-galactoside-binding protein widely distributed in immune and epithelial
      cells, regulates various immune functions and modulates microbial infections.
      Here, we describe galectin-3 up-regulation in mouse lung tissue after challenges
      with the H5N1 influenza virus. We investigated the effects of endogenous galectin
      3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice
      was comparable with wild-type (WT) mice after infections. Compared with infected
      WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and
      reduced IL-1beta levels in bronchoalveolar lavage fluid. In addition, the bone
      marrow-derived macrophages (BMMs) from Gal-3KO mice exhibited reduced
      oligomerization of apoptosis-associated speck-like proteins containing caspase
      associated recruitment domains and secreted less IL-1beta compared with BMMs from
      WT mice. However, similar levels of the inflammasome component of nucleotide
      oligomerization domain-like receptor protein 3 (NLRP3) were observed in two
      genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3
      interaction in BMMs infected with H5N1. An association was also observed between
      galectin-3 and NLRP3/apoptosis-associated speck-like proteins containing caspase
      associated recruitment domain complex. Combined, our results suggest that
      endogenous galectin-3 enhances the effects of H5N1 infection by promoting host
      inflammatory responses and regulating IL-1beta production by macrophages via
      interaction with NLRP3.

PMID- 29366679
TI  - Combination of a Histone Deacetylase 6 Inhibitor and a Somatostatin Receptor
      Agonist Synergistically Reduces Hepatorenal Cystogenesis in an Animal Model of
      Polycystic Liver Disease.
AB  - Hepatic cystogenesis in polycystic liver disease (PLD) is associated with
      abnormalities in multiple cellular processes, including elevated cAMP and
      overexpression of histone deacetylase 6 (HDAC6). Disease progression in
      polycystic kidney (PCK) rats (an animal model of PLD) is attenuated by inhibition
      of either cAMP production or HDAC6. Therefore, we hypothesized that concurrent
      targeting of HDAC6 and cAMP would synergistically reduce cyst growth. Changes in
      hepatorenal cystogenesis were examined in PCK rats treated with a pan-HDAC
      inhibitor, panobinostat; three specific HDAC6 inhibitors, ACY-1215, ACY-738, and
      ACY-241; and a combination of ACY-1215 and the somatostatin receptor analogue,
      pasireotide. We also assessed effects of ACY-1215 and pasireotide alone and in
      combination on cell proliferation, cAMP production, and expression of acetylated
      alpha-tubulin in vitro in cultured cholangiocytes and the length of primary cilia
      and the frequency of ciliated cholangiocytes in vivo in PCK rats. Panobinostat
      and all three HDAC6 inhibitors decreased hepatorenal cystogenesis in PCK rats.
      ACY-1215 was more effective than other HDAC inhibitors and was chosen for
      combinational treatment. ACY-1215 + pasireotide combination synergistically
      reduced cyst growth and increased length of primary cilia in PCK rats. In
      cultured cystic cholangiocytes, ACY-1215 + pasireotide combination concurrently
      decreased cell proliferation and inhibited cAMP levels. These data suggest that
      the combination of drugs that inhibit HDAC6 and cAMP may be an effective therapy
      for PLD.

PMID- 29366680
TI  - Pancreatic and Islet Remodeling in Cystic Fibrosis Transmembrane Conductance
      Regulator (CFTR) Knockout Ferrets.
AB  - In cystic fibrosis (CF), there is early destruction of the exocrine pancreas, and
      this results in a unique form of diabetes that affects approximately half of
      adult CF individuals. An animal model of cystic fibrosis-related diabetes has
      been developed in the ferret, which progresses through phases of glycemic
      abnormalities because of islet remodeling during and after exocrine destruction.
      Herein, we quantified the pancreatic histopathological changes that occur during
      these phases. There was an increase in percentage ductal, fat, and islet area in
      CF ferrets over time compared with age-matched wild-type controls. We also
      quantified islet size, shape, islet cell composition, cell proliferation (Ki-67),
      and expression of remodeling markers (matrix metalloprotease-7, desmin, and alpha
      smooth muscle actin). Pancreatic ducts were dilated with scattered proliferating
      cells and were surrounded by activated stellate cells, indicative of tissue
      remodeling. The timing of islet and duct proliferation, stellate cell activation,
      and matrix remodeling coincided with the previously published stages of glycemic
      crisis and inflammation. This mapping of remodeling events in the CF ferret
      pancreas provides insights into early changes that control glycemic intolerance
      and subsequent recovery during the evolution of CF pancreatic disease.

PMID- 29366681
TI  - Assessing Resident Performance in Screening Mammography: Development of a
      Quantitative Algorithm.
AB  - RATIONALE AND OBJECTIVES: This study aims to provide objective performance data
      and feedback, including examination volumes, recall rates, and concordance with
      faculty interpretations, for residents performing independent interpretation of
      screening mammography examinations. METHOD AND MATERIALS: Residents (r) and
      faculty (f) interpret screening mammograms separately and identify non-callbacks
      (NCBs) and callbacks (CBs). Residents review all discordant results. The number
      of concordant interpretations (fCB-rCB and fNCB-rNCB) and discordant
      interpretations (fCB-rNCB and fNCB-rCB) are entered into a macro-driven
      spreadsheet. These macros weigh the data dependent on the perceived clinical
      impact of the resident's decision. Weighted outcomes are combined with volumes to
      generate a weighted mammography performance score. Rotation-specific goals are
      assigned for the weighted score, screening volumes, recall rate relative to
      faculty, and concordance rates. Residents receive one point for achieving each
      goal. RESULTS: Between July 2013 and May 2017, 18,747 mammography examinations
      were reviewed by 31 residents, in 71 resident rotations, over 246 resident weeks.
      Mean resident recall rate was 9.9% and significantly decreased with resident
      level (R), R2 = 11.3% vs R3 = 9.4%, R4 = 9.2%. Mean resident-faculty discordance
      rate was 10% and significantly decreased from R2 = 12% to R4 = 9.6%. Weighted
      performance scores ranged from 1.1 to 2.0 (mean 1.6, standard deviation 0.17),
      but did not change with rotation experience. Residents had a mean goal
      achievement score of 2.6 (standard deviation 0.47). CONCLUSIONS: This method
      provides residents with easily accessible case-by-case individualized screening
      outcome data over the longitudinal period of their residency, and provides an
      objective method of assessing resident screening mammography performance.

PMID- 29366682
TI  - Dynamic contrast-enhanced (DCE) MRI derived kinetic perfusion indices may help
      predicting seizure control in single calcified neurocysticercosis.
AB  - BACKGROUND: The factors responsible for seizure recurrence in patients with
      Solitary calcified neurocysticercosis (NCC) are not well understood. Blood brain
      barrier (BBB) breach may be associated with seizure recurrence. Dynamic contrast
      enhanced (DCE) MRI derived indices kep, ktrans and ve are useful in quantifying
      BBB permeability. In this study, we assessed the possible role of DCE-MRI and
      matrix metalloproteinases (MMP)-9 levels in predicting seizure recurrence.
      METHODS: In this prospective-observational study, patients with new-onset
      seizures and a solitary calcified NCC were included. DCE-MRI was done to quantify
      BBB integrity. DCE-MRI parameters were measured as kep, ktrans and ve. MMP-9
      levels were estimated. Patients were followed for 1 year, when DCE-MRI and MMP-9
      levels were repeated. Patients were classified into two groups on the basis of
      seizure recurrence, which was defined as the recurrence of an episode of seizure
      at least 1 week after the initiation of the anti-epileptic drugs. Logistic
      regression analysis was done. RESULTS: At 1-year of follow up, 8 out of 32
      patients had seizure recurrence. Baseline DCE-MRI derived kep (p = 0.015) and MMP
      9 levels (p = 0.019) were significantly higher in the seizure "recurrence" group
      compared with the "no recurrence" group. On within-group analysis, a significant
      increase in kep (p = 0.012), ve (p = 0.012), and MMP-9 levels (p = 0.017) was
      observed in the seizure "recurrence" group while a decrease was seen in ve and
      MMP-9 levels in the "no recurrence" group. CONCLUSION: Higher values of DCE-MRI
      indices and MMP-9 levels, with a corresponding trend in the follow-up, can be
      useful in predicting lesions with a higher propensity for seizure recurrence.

PMID- 29366683
TI  - CHASEing Cytokinin Receptors in Plants, Bacteria, Fungi, and Beyond.
AB  - Cytokinin (CK) signaling pathways were believed to be restricted to terrestrial
      plants. However, the identification of CK receptor homologs in phytopathogenic
      bacteria, cyanobacteria, and early diverging fungi has recently been reported. CK
      signaling in prokaryotic and non-plant eukaryotic organisms sheds new light on
      the dissemination and evolution of this hormone.

PMID- 29366684
TI  - Signaling Peptides and Receptors Coordinating Plant Root Development.
AB  - Small peptides mediate cell-cell communication to coordinate a variety of plant
      developmental processes. Signaling peptides specifically bind to the
      extracellular domains of receptors that belong to the receptor-like kinase
      family, and the peptide-receptor interaction activates a range of biochemical and
      physiological processes. The plant root is crucial for the anchorage of plants in
      soil as well as for the uptake of water and nutrients. Over recent years great
      progress has been made in the identification of receptors, structural analysis of
      peptide-receptor pairs, and characterization of their signaling pathways during
      plant root development. We review here recent advances in the elucidation of the
      functions and molecular mechanisms of signaling peptides, the peptide-receptor
      pairs that activate signal initiation, and their signaling pathways during root
      development.

PMID- 29366685
TI  - Back to the Future.

PMID- 29366686
TI  - Commentary on "A Prospective Study to Evaluate Complete Wound Healing and Limb
      Salvage Rates After Angiosome Targeted Infrapopliteal Balloon Angioplasty in
      Critical Limb Ischaemia Patients".

PMID- 29366687
TI  - Densely functionalised spirocyclic oxetane-piperidine scaffolds for drug
      discovery.
AB  - A spirocyclic, sp3-atom rich oxetane-containing scaffold was synthesised in just
      two steps via a gold catalysed propargylic alcohol rearrangement. The key gold
      cyclisation can be undertaken on a 40 g scale allowing the preparation of 419
      lead-like compounds based on the scaffold for the European Lead Factory.

PMID- 29366688
TI  - Solid-State NMR of highly 13C-enriched cholesterol in lipid bilayers.
AB  - Cholesterol (Chol) is vital for cell function as it is essential to a myriad of
      biochemical and biophysical processes. The atomistic details of Chol's
      interactions with phospholipids and proteins is therefore of fundamental
      interest, and NMR offers unique opportunities to interrogate these properties at
      high resolution. Towards this end, here we describe approaches for examining the
      structure and dynamics of Chol in lipid bilayers using high levels of 13C
      enrichment in combination with magic-angle spinning (MAS) methods. We quantify
      the incorporation levels and demonstrate high sensitivity and resolution in 2D
      13C-13C and 1H-13C spectra, enabling de novo assignments and site-resolved order
      parameter measurements obtained in a fraction of the time required for
      experiments with natural abundance sterols. We envision many potential future
      applications of these methods to study sterol interactions with drugs, lipids and
      proteins.

PMID- 29366689
TI  - In vivo study of teratogenic and anticonvulsant effects of antiepileptics drugs
      in zebrafish embryo and larvae.
AB  - Epilepsy is a neurological disorder treated with antiepileptic drugs (AEDs).
      Since AEDs are administered in women in childbearing age, it is critical to study
      if drugs are capable of inducing developmental toxicity. Along the bibliography
      available, there is no research comparing teratogenicity and anticonvulsant
      effect within the same study. In the present study, we evaluated the teratogenic
      and anticonvulsant effects of six different AEDs: carbamazepine, levetiracetam,
      lamotrigine, phenobarbital, phenytoin and valproic acid. Zebrafish was the
      selected animal model because of its small size, rapid external development and
      similar neurophysiology to mammals. Zebrafish embryo and larvae were exposed to
      AEDs. Embryo development was monitored by their hatching and morphology. In
      larvae, locomotor activity was measured as a parameter of neurotoxicity. Finally,
      anticonvulsant effect was determined after exposure to AEDs in zebrafish larvae
      treated with the proconvulsant drug pentylenetetrazole. Our results suggest that
      lamotrigine and phenytoin could be suitable non-teratogenic and efficient
      anticonvulsant options for epilepsy treatment.

PMID- 29366690
TI  - Comparative neurotoxicity study of mercury-based inorganic compounds including
      Ayurvedic medicines Rasasindura and Kajjali in zebrafish model.
AB  - Zebrafish behavioral model is a powerful tool for neuroscience research.
      Behavioral changes in the zebrafish are studied by administering drugs. With the
      aid of automated and open-source MATLAB program, high-accuracy tracking of
      zebrafish can be achieved, and the important behavioral parameters can be
      calculated. Although mercury is accepted as a potent neurotoxin, used as a key
      element for preparing certain Ayurvedic medicines. In this work, mercury-based
      inorganic compounds, including HgCl2, HgS, and Ayurvedic medicines (Rasasindura
      and Kajjali) were administrated in zebrafish, and the effects on various
      behavioral parameters and cortisol levels were studied. A significant change in
      the basic locomotor parameters of fish was observed including speed (43%
      reduction), meander (150% increment), and a number of freeze points (125%
      increment), during 5-day treatment of HgCl2 along with a 3-fold increase in
      cortisol level against the control groups. Abnormal behavior was also recorded in
      color preference test, and novel tank diving behavior of HgCl2-treated groups,
      which can be attributed to the neurotoxicity induced by the HgCl2 administration.
      Contrary to this, the Rasasindura-treated group showed a significant increase in
      speed by 33%, decrease in meander by 20%, decrease in freeze points by 30%, and
      insignificant alteration in cortisol levels, which can be related to the
      rejuvenating nature of the Ayurvedic medicine Rasasindura. Additionally, Kajjali
      treated group did not show any substantial changes in zebrafish cortisol level
      and behavioral parameters except one in the diving test that indicates lowering
      stress. Similarly, HgS group showed normal behaviors except two irregular motor
      behaviors identical with the HgCl2 group. From these results, it can be concluded
      that the mercury-based Ayurvedic Rasasindura and Kajjali did not show any adverse
      effect or toxicity on zebrafish behavior model.

PMID- 29366691
TI  - Endophthalmitis caused by Purpureocillium lilacinum.

PMID- 29366692
TI  - An oil refinery worker at Kaohsiung, with Pseudoxanthomonas kaohsiungensis
      bloodstream infection presenting as chronic pericarditis and masquerading as
      tuberculosis pericarditis.

PMID- 29366693
TI  - Rapid flow-through enzyme immunoassay of progesterone in whole cows' milk.
AB  - A rapid flow-through immunoassay using an enzyme (horseradish peroxidase) as a
      label for quantitative and semi-quantitative determination of progesterone in
      whole cows' milk was developed. The flow-through test device consisted of a
      porous nitrocellulose membrane coated with antibodies and an absorbent membrane.
      The substrate solution containing 3,3',5,5' -tetramethylbenzidine was used for
      colour visualization. The detection limit of 0.4 ng/mL P4 was obtained by this
      method; analysis time did not exceed 15 min. To eliminate matrix interference a
      simple sample preparation procedure was used. Results of analysis of whole cows'
      milk samples with flow-through method were in good correlation with ELISA results
      (R = 0.96, n = 34). The developed rapid flow-through test system showed high
      efficiency for the determination of progesterone level in whole cow's milk and
      can be used on-site for quick identification of milk samples with low and high
      progesterone concentration.

PMID- 29366694
TI  - Novel volumetric adsorptive microsampling technique for determination of
      perfluorinated compounds in blood.
AB  - Microsampling is an attractive option for significantly reducing the volume of
      blood taken for chemical analysis allowing for blood samples taken as a 'finger
      prick' with a lancet. A novel, volumetric adsorptive microsampling (VAMSTM)
      device, which reproducibly collects a small volume of 10 MUL whole blood in a
      hematocrit-independent manner, is evaluated in a human biomonitoring setting, and
      has been utilized for analysis of several perfluoroalkyl acids (PFAA). The
      results show that the VAMS technique is applicable for PFAA analysis, method has
      good linearity, repeatability, accuracy and is sufficiently sensitive for samples
      from general populations. The stability of PFAAs with VAMS devices is shown to be
      acceptable, which supports the sampling and transportation strategy of several
      study designs. Furthermore, as well as allowing for a quick and efficient
      extraction and analysis flow path, the VAMS microsampler is an easy to use device
      in a real-world sample collection scenario.

PMID- 29366695
TI  - Pharmacist training in suicide prevention.
AB  - OBJECTIVE: Suicide in the United States is a major preventable public health
      problem. Pharmacists need to be educated on suicide prevention strategies so that
      they can increase their own awareness and identify patients at-risk. A training
      program for pharmacists was used to provide skills necessary to recognize a
      crisis and the warning signs of suicide. The program's effect on the
      participant's general perception, self-efficacy, and attitude towards suicide
      prevention was examined. SETTING: Various academic, health care, and professional
      meetings throughout San Diego County. PRACTICE INNOVATION: First Question,
      Persuade, and Refer training program targeting pharmacists. EVALUATION: A self
      administered presurvey, postsurvey and, Program Outcome Evaluation were given to
      participants of the suicide training program. Items included demographics,
      general perception, self-efficacy, and attitude toward suicide prevention.
      Descriptive statistics were used to describe participants' demographics. t tests
      were used to compare general perception, attitudes, and self-efficacy scores
      between pretest and post-program evaluation survey responses. Nonparametric
      Wilcoxon signed rank analyses for matched pairs were used to compare survey
      responses that asked about attitudes before and after trainings. Regression
      analyses were conducted to assess factors associated with general perception,
      self-efficacy, and attitudes. RESULTS: Participants were more likely to update
      knowledge after training and reported more confidence to make an intervention for
      a patient at risk for suicide. CONCLUSION: Our findings suggest that a suicide
      prevention training program helped pharmacist respondents build confidence in
      several self-efficacy areas relating to detection of suicide signs, response to
      patients with suicidal thoughts, reassurance for patients, and provision of
      resources and referrals.

PMID- 29366696
TI  - Assessment of the benefits of and barriers to HIV pharmacist credentialing.
AB  - OBJECTIVES: To ascertain the reasons for, benefits of, and barriers to pursuing
      the American Academy of HIV Medicine (AAHIVM) HIV Pharmacist (AAHIVP) credential.
      METHODS: A cross-sectional study using an electronic self-administered survey was
      used. Two separate invitations to participate in online surveys were sent to
      pharmacists who practice in HIV-related settings: 1 to pharmacists with the
      AAHIVP credential and 1 to members of key pharmacy organizations and employers
      without the credential. The surveys assessed demographics, concurrent credentials
      and certifications, and factors influencing the pursuit of and benefits gained
      from having the AAHIVP credential (credentialed population) or barriers to
      pursuing the AAHIVP credential (credentialed and noncredentialed populations).
      RESULTS: There were 192 participants (survey response rate 38.8%) in the
      credentialed population and 212 participants in the noncredentialed population.
      Perceived recognition as an HIV expert from pharmacist (n = 174; 90.6%) and
      physician (n = 162; 84.4%) peers was the main reason for credentialing; only
      20.4% (n = 23/113) of participants' employers reimbursed for the credential.
      Common reasons for nonpursuit included lack of employer incentive (n = 46; 26.6%)
      and lack of fee reimbursement (n = 38; 21.9%) in those aware of the credential.
      However, a majority of these noncredentialed participants reported they would be
      interested in pursuing credentialing (n = 152; 80.4%). CONCLUSION: AAHIVP
      credentialing is sought and maintained on the basis of perceived intangible
      benefits, such as peer recognition, over tangible benefits, such as increased
      salary and reimbursement by third-party payers. Despite interest, a lack of
      employer reimbursement is perceived to be a barrier to AAHIVP credentialing among
      those who have not yet been credentialed.

PMID- 29366698
TI  - Neural source dynamics of brain responses to continuous stimuli: Speech
      processing from acoustics to comprehension.
AB  - Human experience often involves continuous sensory information that unfolds over
      time. This is true in particular for speech comprehension, where continuous
      acoustic signals are processed over seconds or even minutes. We show that brain
      responses to such continuous stimuli can be investigated in detail, for
      magnetoencephalography (MEG) data, by combining linear kernel estimation with
      minimum norm source localization. Previous research has shown that the
      requirement to average data over many trials can be overcome by modeling the
      brain response as a linear convolution of the stimulus and a kernel, or response
      function, and estimating a kernel that predicts the response from the stimulus.
      However, such analysis has been typically restricted to sensor space. Here we
      demonstrate that this analysis can also be performed in neural source space. We
      first computed distributed minimum norm current source estimates for continuous
      MEG recordings, and then computed response functions for the current estimate at
      each source element, using the boosting algorithm with cross-validation.
      Permutation tests can then assess the significance of individual predictor
      variables, as well as features of the corresponding spatio-temporal response
      functions. We demonstrate the viability of this technique by computing spatio
      temporal response functions for speech stimuli, using predictor variables
      reflecting acoustic, lexical and semantic processing. Results indicate that
      processes related to comprehension of continuous speech can be differentiated
      anatomically as well as temporally: acoustic information engaged auditory cortex
      at short latencies, followed by responses over the central sulcus and inferior
      frontal gyrus, possibly related to somatosensory/motor cortex involvement in
      speech perception; lexical frequency was associated with a left-lateralized
      response in auditory cortex and subsequent bilateral frontal activity; and
      semantic composition was associated with bilateral temporal and frontal brain
      activity. We conclude that this technique can be used to study the neural
      processing of continuous stimuli in time and anatomical space with the
      millisecond temporal resolution of MEG. This suggests new avenues for analyzing
      neural processing of naturalistic stimuli, without the necessity of averaging
      over artificially short or truncated stimuli.

PMID- 29366699
TI  - A meta-analytical review of brain activity associated with intertemporal
      decisions: Evidence for an anterior-posterior tangibility axis.
AB  - In temporal discounting experiments, subjects are repeatedly presented with
      option sets in which they must choose between receiving a small amount of money
      sooner (SmallerSooner) or a larger amount of money at a more distant point in
      time (LargerLater). Although over 50 temporal discounting experiments using fMRI
      are described in literature, there has not been a meta-analysis identifying
      regions activated when subjects choose SmallerSooner versus LargerLater
      alternatives. Evidence suggests a prefrontal cortex 'abstraction hierarchy', from
      abstract planning in more anterior regions to concrete processing in posterior
      regions. Because abstraction has been linked with making LargerLater choices, we
      hypothesized an association between LargerLater choices and more anterior
      prefrontal cortex activity, and an association between SmallerSooner choices and
      more posterior activity. Across thirteen fMRI temporal discounting studies
      including 436 subjects, we observed LargerLater activity anterior of
      SmallerSooner activity, both in the left inferior frontal gyrus pars
      triangularis, consistent with our pre-registered hypothesis. We call for further
      work linking temporal discounting and hierarchical processing of abstract and
      concrete information in the prefrontal cortex.

PMID- 29366697
TI  - Predicting future learning from baseline network architecture.
AB  - Human behavior and cognition result from a complex pattern of interactions
      between brain regions. The flexible reconfiguration of these patterns enables
      behavioral adaptation, such as the acquisition of a new motor skill. Yet, the
      degree to which these reconfigurations depend on the brain's baseline
      sensorimotor integration is far from understood. Here, we asked whether
      spontaneous fluctuations in sensorimotor networks at baseline were predictive of
      individual differences in future learning. We analyzed functional MRI data from
      19 participants prior to six weeks of training on a new motor skill. We found
      that visual-motor connectivity was inversely related to learning rate:
      sensorimotor autonomy at baseline corresponded to faster learning in the future.
      Using three additional scans, we found that visual-motor connectivity at baseline
      is a relatively stable individual trait. These results suggest that individual
      differences in motor skill learning can be predicted from sensorimotor autonomy
      at baseline prior to task execution.

PMID- 29366700
TI  - Umbilical cord blood transplantation without in vivo T-cell depletion for
      children with MHC class II deficiency.

PMID- 29366701
TI  - Basophils from allergic patients are neither hyperresponsive to activation
      signals nor hyporesponsive to inhibition signals.
AB  - BACKGROUND: Basophil activation contributes to inflammatory reactions, especially
      in allergy. It is controlled, both positively and negatively, by several
      mechanisms. High-affinity IgE receptors (FcepsilonRI) generate a mixture of
      activation and inhibition signals when aggregated, the ratio of which depends on
      the concentration of allergen recognized by receptor-bound IgE. Low-affinity IgG
      receptors (FcgammaRIIA/B) generate inhibition signals when coengaged with
      FcepsilonRI by allergen-antibody immune complexes. Commensal and probiotic
      bacteria, such as Lactobacillus paracasei, generate inhibition signals through
      still unclear mechanisms. OBJECTIVE: We sought to investigate whether mechanisms
      that control, both positively and negatively, basophil activation, which were
      unraveled and studied in basophils from healthy donors, are functional in
      allergic patients. METHODS: FcepsilonRI and FcgammaRIIA/B expression, FcepsilonRI
      dependent activation, FcepsilonRI-dependent inhibition, and FcgammaRIIB-dependent
      inhibition were examined in blood basophils incubated overnight with or without L
      paracasei and challenged under 10 experimental conditions. Basophils from healthy
      donors were compared with basophils from patients who consulted an allergology
      outpatient clinic over a period of 3 months with respiratory allergy, anaphylaxis
      antecedents, chronic urticaria, and/or atopic dermatitis. RESULTS: Patients'
      basophils expressed neither more FcepsilonRI nor less FcgammaRIIB than basophils
      from healthy donors. They were neither hyperreactive to positive regulation nor
      hyporeactive to negative regulation, irrespective of the receptors or mechanisms
      involved and the allergic manifestations of the patients. CONCLUSION: Regulatory
      mechanisms that control basophil activation are fully functional in allergic
      patients. Intrinsic defects in these mechanisms do not explain allergic
      manifestations. Based on these mechanisms, immune checkpoint modifiers can be
      developed as novel therapeutic tools for allergy.

PMID- 29366702
TI  - Human dendritic cell subset 4 (DC4) correlates to a subset of CD14dim/-CD16++
      monocytes.

PMID- 29366703
TI  - Evidence for single-dose protection by the bivalent HPV vaccine-Review of the
      Costa Rica HPV vaccine trial and future research studies.
AB  - The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial,
      provided the initial data that one dose of the HPV vaccine could provide durable
      protection against HPV infection. Although the study design was to administer all
      participants three doses of HPV or control vaccine, 20% of women did not receive
      the three-dose regimens, mostly due to involuntary reasons unrelated to
      vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine
      could be as efficacious as three doses of the vaccine using the endpoint of
      persistent HPV infection accumulated over the first four years of the trial;
      findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody
      levels after one dose, although lower than levels elicited by three doses, were 9
      times higher than levels elicited by natural infection. Importantly, levels
      remained essentially constant over at least seven years, suggesting that the
      observed protection provided by a single dose might be durable. Much work has
      been done to assure these non-randomized findings are valid. Yet, the group of
      recipients who received one dose of the bivalent HPV vaccine in the CVT and
      PATRICIA trials was small and not randomly selected nor blinded to the number of
      doses received. The next phase of research is to conduct a formal randomized,
      controlled trial to evaluate the protection afforded by a single dose of HPV
      vaccine. Complementary studies are in progress to bridge our findings to other
      populations, and to further document the long-term durability of antibody
      response following a single dose.

PMID- 29366705
TI  - Determinants of the receipt of the 9-valent human papillomavirus vaccine in the
      first year after introduction in North Carolina.
AB  - OBJECTIVES: The objective of this study was to describe the transition from bi-
      and quadrivalent HPV vaccines to 9vHPV in aggregate and identify determinants of
      the receipt of 9vHPV among youth following the introduction of 9vHPV in North
      Carolina. METHODS: The study used a retrospective cohort design with data from
      the North Carolina Immunization Registry (NCIR). Our sample included all doses of
      HPV vaccine administered between July 2015 and October 2016 to age-eligible youth
      (ages 9-17). We used a logistic regression model to associate individual child
      level and ZIP Code Tabulation Area (ZCTA)-level characteristics with an indicator
      variable for receiving 9vHPV (vs. other HPV vaccines). RESULTS: Youth receiving
      the HPV vaccine were more likely to receive 9vHPV if they lived in a ZCTA with a
      larger age-eligible (i.e., 9-17) population, a health professional shortage area,
      or a higher number of annual outpatient visits per capita. They were less likely
      to receive 9vHPV if they were older, received a publicly-funded dose, or lived in
      a ZCTA with a higher percentage of the population with less than a high-school
      education or a higher number of religious organizations. CONCLUSIONS: While the
      transition from other HPV vaccines to 9vHPV was relatively quick, there were
      disparities in the diffusion of 9vHPV across North Carolina.

PMID- 29366704
TI  - Modeling the impact of combined vaccination programs against varicella and herpes
      zoster in Norway.
AB  - BACKGROUND: Adoption of varicella immunization in Europe is limited due to a
      predicted increase in the incidence of herpes zoster (HZ) resulting from a
      removal of exogenous boosting by varicella vaccination. Most available
      assessments of immunization strategies only considered universal varicella
      vaccination (alone or in combination with HZ by the live vaccine). The
      development of a new subunit recombinant zoster vaccine may provide new
      perspectives of HZ control. METHODS: We used a mathematical model for VZV in
      Norway based on the progressive immunity formulation of exogenous boosting. We
      evaluated a complete range of alternative immunization options against varicella
      and HZ including both universal and targeted varicella vaccination, either alone
      or with zoster immunization, and zoster immunization alone. We considered all
      values of the boosting intensity consistent with the Norwegian HZ incidence and
      compared the performance of the currently available live vaccine vs. a new
      recombinant vaccine. RESULTS: Universal varicella vaccination alone resulted in a
      marked increase in the incidence of HZ under all scenarios considered. Even under
      the most favorable hypotheses on the magnitude of the boosting intensity, this
      increase could be mitigated only by a parallel HZ immunization with a recombinant
      vaccine, assuming a long duration of protection. Targeted varicella immunization
      of adolescents resulted in a modest increase in the HZ incidence which could be
      counterbalanced by both the live and, especially, the recombinant vaccine.
      CONCLUSIONS: Given current knowledge on HZ pathogenesis and exogenous boosting,
      targeted varicella vaccination of adolescents was the only strategy that was not
      predicted to impact the epidemiology of HZ, and therefore it may represent a
      suitable alternative to universal vaccination. These results are aimed to support
      vaccine policy decisions in Norway and other countries with a similar VZV
      epidemiology.

PMID- 29366706
TI  - Vaccine financing and billing in practices serving adult patients: A follow-up
      survey.
AB  - BACKGROUND: Financial concerns are often cited by physicians as a barrier to
      administering routinely recommended vaccines to adults. The purpose of this study
      was to assess perceived payments and profit from administering recommended adult
      vaccines and vaccine purchasing practices among general internal medicine (GIM)
      and family medicine (FM) practices in the United States. METHODS: We conducted an
      interviewer-administered survey from January-June 2014 of practices stratified by
      specialty (FM or GIM), affiliation (standalone or >= 2 practice sites), and level
      of financial decision-making (independent or larger system level) in FM and GIM
      practices that responded to a previous survey on adult vaccine financing and
      provided contact information for follow-up. Practice personnel identified as
      knowledgeable about vaccine financing and billing responded to questions about
      payments relative to vaccine purchase price and payment for vaccine
      administration, perceived profit on vaccination, claim denial, and utilization of
      various purchasing strategies for private vaccine stocks. Survey items on payment
      and perceived profit were assessed for various public and private payer types.
      Descriptive statistics were calculated and responses compared by physician
      specialty, practice affiliation, and level of financial decision-making. RESULTS:
      Of 242 practices approached, 43% (n = 104) completed the survey. Reported payment
      levels and perceived profit varied by payer type. Only for preferred provider
      organizations did a plurality of respondents report profiting on adult
      vaccination services. Over half of respondents reported losing money vaccinating
      adult Medicaid beneficiaries. One-quarter to one-third of respondents reported
      not knowing about Medicare Part D payment levels for vaccine purchase and vaccine
      administration, respectively. Few respondents reported negotiating with
      manufacturers or insurance plans on vaccine purchase prices or payments for
      vaccination. CONCLUSIONS: Practices vaccinating adults may benefit from education
      and technical assistance related to vaccine financing and billing and greater use
      of purchasing strategies to decrease upfront vaccine cost.

PMID- 29366707
TI  - Vaccination of pigs with a codon-pair bias de-optimized live attenuated influenza
      vaccine protects from homologous challenge.
AB  - Influenza A virus (IAV) in swine constitutes a major economic burden for
      producers as well as a potential threat to public health. Whole inactivated virus
      vaccines (WIV) are the predominant countermeasure employed to control IAV in
      swine herds in the United States despite the superior protection, and diminished
      adverse effects, induced by live attenuated influenza vaccines (LAIV). A major
      hurdle for the development of LAIV exists in achieving the proper level of
      attenuation while maintaining immunogenicity. Using Synthetic Attenuated Virus
      Engineering (SAVE) to introduce codon-pair bias de-optimization (CPBD) into the
      hemagglutinin (HA) and neuraminidase (NA) gene segments of pandemic H1N1 IAV, a
      novel LAIV was produced and evaluated for attenuation, immunogenicity, and
      efficacy in pigs. The CPBD LAIV induced inappreciable pathology following
      intranasal administration yet induced robust serum and mucosal antibody titers.
      CPBD LAIV vaccinated pigs challenged with wild-type virus showed protection from
      disease and virus detection, highlighted by the absence of detectable virus
      titers in the nasal passages and lungs. These results demonstrate the efficacy of
      a LAIV designed by SAVE codon de-optimization in pigs, providing support for the
      continued development of CPBD LAIV for use in swine.

PMID- 29366708
TI  - Human papillomavirus vaccine motivators and barriers among community college
      students: Considerations for development of a successful vaccination program.
AB  - BACKGROUND: Previous interventions in colleges to improve human papillomavirus
      (HPV) vaccination have not been highly successful. Although barriers have been
      assessed in traditional colleges, less is known about vaccination barriers in
      community colleges. METHODS: We approached students aged 18-26 years old enrolled
      at a community college for an in-person semi-structured qualitative interview on
      HPV vaccination and health, with questions guided by the Theory of Planned
      Behavior. Data collection took place between April 2015 and December 2015.
      Thematic analysis techniques were used to analyze the data. RESULTS: During
      interviews with 19 students, 4 themes emerged, including: general vaccine
      attitudes, barriers to HPV vaccination, motivators to HPV vaccination, and social
      influences. Participants felt that vaccines were beneficial, but were concerned
      about side effects. They felt that getting the HPV vaccine would be inconvenient,
      and they did not know enough about it to decide. Most would not trust their
      friends' opinions, but would want to know about side effects that their
      vaccinated friends experienced. CONCLUSIONS: Successful interventions at
      community colleges should include several components to increase convenience as
      well as utilize interactive methods to promote HPV vaccine awareness.

PMID- 29366709
TI  - Recombinant live attenuated avian coronavirus vaccines with deletions in the
      accessory genes 3ab and/or 5ab protect against infectious bronchitis in chickens.
AB  - Avian coronavirus infectious bronchitis virus (IBV) is a respiratory pathogen of
      chickens, causing severe economic losses in poultry industry worldwide. Live
      attenuated viruses are widely used in both the broiler and layer industry because
      of their efficacy and ability to be mass applied. Recently, we established a
      novel reverse genetics system based on targeted RNA recombination to manipulate
      the genome of IBV strain H52. Here we explore the possibilities to attenuate IBV
      in a rational way in order to generate safe and effective vaccines against
      virulent IBV (van Beurden et al., 2017). To this end, we deleted the nonessential
      group-specific accessory genes 3 and/or 5 in the IBV genome by targeted RNA
      recombination and selected the recombinant viruses in embryonated eggs. The
      resulting recombinant (r) rIBV-Delta3ab, rIBV-Delta5ab, and rIBV-Delta3ab5ab
      could be rescued and grew to the same virus titer as recombinant and wild type
      IBV strain H52. Thus, genes 3ab and 5ab are not essential for replication in ovo.
      When administered to one-day-old chickens, rIBV-Delta3ab, rIBV-Delta5ab, and rIBV
      Delta3ab5ab showed reduced ciliostasis as compared to rIBV H52 and wild type H52,
      indicating that the accessory genes contribute to the pathogenicity of IBV. After
      homologous challenge with the virulent IBV strain M41, all vaccinated chickens
      were protected against disease based on reduced loss of ciliary movement in the
      trachea compared to the non-vaccinated but challenged controls. Taken together,
      deletion of accessory genes 3ab and/or 5ab in IBV resulted in mutant viruses with
      an attenuated phenotype and the ability to induce protection in chickens. Hence,
      targeted RNA recombination based on virulent IBV provides opportunities for the
      development of a next generation of rationally designed live attenuated IBV
      vaccines.

PMID- 29366710
TI  - Rotavirus hospitalizations among children <5 years of age-Tajikistan, 2013-2014.
AB  - BACKGROUND: In January 2015, Tajikistan introduced the monovalent rotavirus
      vaccine into the national immunization program. Our objective was to estimate pre
      vaccine burden of rotavirus-associated hospitalizations in children <5 years of
      age in Tajikistan. METHODS: During January 2013-December 2014, active
      surveillance for acute gastroenteritis (AGE)-associated hospitalizations in
      children <5 years of age was conducted by sentinel surveillance site staff.
      Patients' demographic and clinical data were summarized and a stool sample was
      collected. An Enzyme Linked Immunosorbent Assay was used for diagnosis of
      rotavirus infection and subset of the specimens was sent for polymerase chain
      reaction (PCR) genotyping. RESULTS: Of 2860 eligible children enrolled and
      tested, 1207 (42%) were positive for rotavirus. An increase in the number and
      proportion of rotavirus cases attributed to rotavirus season, with positivity
      rates >40%, was annually observed during June-September. The median age of
      rotavirus patients was 9 months and 939/1207 (78%) rotavirus patients were aged 6
      23 months. Most (1097/1203; 91%) rotavirus patients were treated with intravenous
      fluids. G1P[8] was the predominant genotype during both years of surveillance,
      accounting for 133/222 (60%) of genotyped cases. CONCLUSION: Rotavirus is a major
      cause of hospitalization due to severe AGE in children <5 years of age in
      Tajikistan, accounting for >40% of cases. Continued, enhanced rotavirus
      surveillance may allow documentation of changes in rotavirus disease burden
      following vaccine introduction and assessment of vaccine effectiveness.

PMID- 29366711
TI  - Screening for recommended antenatal risk factors: How long does it take?
AB  - BACKGROUND: Detection and management of antenatal risk factors is critical for
      quality care. AIMS: To determine (1) women's views about when they should be
      asked about antenatal health factors as recommended in the Australian antenatal
      guidelines; and (2) the time required to provide recommended care using a
      clinical scenario. METHODS: In Phase 1, pregnant women attending an outpatient
      obstetrics clinic at a public hospital were surveyed about preferred screening
      for antenatal risk factors during visit(s). In Phase 2, a hypothetical clinical
      scenario of a woman attending her first antenatal visit with a practising midwife
      was video-recorded to extrapolate the time taken to ask about and offer
      assistance to manage clinical, screening and lifestyle risk factors. FINDINGS:
      Most women (96%) perceived they should be asked about each of the risk factors at
      least once (i.e. at first visit). Total time taken to ask about all risk factors
      was 52min. More time was spent discussing clinical (11min) than lifestyle factors
      (4min). Adjusting for the estimated prevalence of each risk factor, the time
      taken to offer assistance was 8min per woman. Average time required for detecting
      and offering assistance to manage risk factors is 60min per average risk woman.
      CONCLUSION: Women are willing to be asked about risk factors; however this
      process is time-consuming. Strategies to streamline visits and prioritise
      recommendations so time-efficient yet comprehensive care can be delivered are
      needed, particularly when factors require monitoring over time and for those who
      may be 'at-risk' for multiple factors.

PMID- 29366712
TI  - Selection of the Best of 2017 in Interventional Cardiology: Revolution in the
      Study of Coronary Physiology and New Parameters.

PMID- 29366713
TI  - Selection of the Best of 2017 in Congenital Heart Disease.

PMID- 29366714
TI  - Achilles and the tortoise: Some caveats to mathematical modeling in biology.
AB  - Mathematical modeling has recently become a much-lauded enterprise, and many
      funding agencies seek to prioritize this endeavor. However, there are certain
      dangers associated with mathematical modeling, and knowledge of these pitfalls
      should also be part of a biologist's training in this set of techniques. (1)
      Mathematical models are limited by known science; (2) Mathematical models can
      tell what can happen, but not what did happen; (3) A model does not have to
      conform to reality, even if it is logically consistent; (4) Models abstract from
      reality, and sometimes what they eliminate is critically important; (5)
      Mathematics can present a Platonic ideal to which biologically organized matter
      strives, rather than a trial-and-error bumbling through evolutionary processes.
      This "Unity of Science" approach, which sees biology as the lowest physical
      science and mathematics as the highest science, is part of a Western belief
      system, often called the Great Chain of Being (or Scala Natura), that sees
      knowledge emerge as one passes from biology to chemistry to physics to
      mathematics, in an ascending progression of reason being purification from
      matter. This is also an informal model for the emergence of new life. There are
      now other informal models for integrating development and evolution, but each has
      its limitations.

PMID- 29366715
TI  - Diarrhea and related factors among passengers on world cruises departing from
      Japan.
AB  - BACKGROUND: Despite growth in the number of cruises worldwide, evidence about
      diarrhea experienced by cruise ship passengers remains sparse. We investigated
      rates of diarrhea and related factors among passengers on world cruises departing
      from Japan. METHODS: Targeting passengers on five world cruises (n = 4180) from
      2012 to 2013 (85-103 travel days), we calculated rates of health seeking behavior
      for diarrhea by sex, age group, and number of roommates for each cruise. We
      estimated rate ratios and 95% confidence intervals, using the group aged 20-39
      years, women, and 2-4 roommates as referent categories. RESULTS: We found 5.04
      6.00 cases per 10,000 person-days in the five cruises, with an elevated number
      after calling at ports. Older passengers (>60 years) and passengers with fewer
      roommates had an elevated risk of health seeking behavior for diarrhea, although
      passengers aged <20 years had an elevated risk on one cruise. After controlling
      for covariates (including cruise), significant associations remained for
      passengers aged >60 years and without roommates. CONCLUSIONS: Older passengers
      and passengers with fewer roommates may be more likely to seek medical treatment
      for diarrhea during travel on a world cruise, and should take preventive
      measures.

PMID- 29366716
TI  - Spotiton: New features and applications.
AB  - We present an update describing new features and applications of Spotiton, a
      novel instrument for vitrifying samples for cryoEM. We have used Spotiton to
      prepare several test specimens that can be reconstructed using routine single
      particle analysis to ~3 A resolution, indicating that the process has no apparent
      deleterious effect on the sample integrity. The system is now in routine and
      continuous use in our lab and has been used to successfully vitrify a wide
      variety of samples.

PMID- 29366717
TI  - Gastric sleeve migration conversion to a Roux-en-Y gastric bypass in combination
      with wedge fundectomy and paraesophageal hernia repair.

PMID- 29366718
TI  - Production of aminoacyl prolines using the adenylation domain of nonribosomal
      peptide synthetase with class III polyphosphate kinase 2-mediated ATP
      regeneration.
AB  - An ATP regeneration system is advantageous for industrial processes that are
      coupled with ATP-dependent enzymes. For ATP regeneration from AMP, a few methods
      have been reported; however, these methods employ multiple enzymes. To establish
      an ATP regeneration system using a single enzyme, we focused on class III
      polyphosphate kinase 2 (class III PPK2) that can synthesize ATP from AMP and
      polyphosphate. We constructed an ATP regeneration system from AMP using
      Deipr_1912, a class III PPK2 from Deinococcus proteolyticus NBRC 101906T, coupled
      with aminoacyl proline (Xaa-Pro) synthesis catalyzed by the adenylation domain of
      tyrocidine synthetase A (TycA-A). Using this system, 0.87 mM of l-Trp-l-Pro was
      successfully synthesized from AMP after 72 h. Farther, addition of inorganic
      pyrophosphatase from Escherichia coli to the coupling reaction increased the
      reaction rate by 14-fold to yield 6.2 mM l-Trp-l-Pro. When the coupling reaction
      was applied to whole-cell reactions in E. coli BL21(DE3) pepQ-putA-, ATP was
      successfully regenerated from AMP by Deipr_1912, and 6.7 mM of l-Trp-l-Pro was
      produced after 24 h with the supplementation of 10 mM AMP. In addition, by
      altering the substrate amino acid of TycA-A, not only l-Trp-l-Pro, but also
      various other l-Xaa-l-Pro (Xaa = Val, Leu, Met, or Tyr) were produced using the
      whole-cell reaction incorporating ATP regeneration. Therefore, a production
      method for Xaa-Pro employing the adenylation domain of a nonribosomal peptide
      synthetase was established by introducing an ATP regeneration system that
      utilizes class III PPK2 with pyrophosphatase.

PMID- 29366719
TI  - Microbe participation in aroma production during soy sauce fermentation.
AB  - Soy sauce is a traditional Japanese fermented seasoning that contains various
      constituents such as amino acids, organic acids, and volatiles that are produced
      during the long fermentation process. Although studies regarding the correlation
      between microbes and aroma constituents have been performed, there are no reports
      about the influences of the microbial products, such as lactic acid, acetic acid,
      and ethanol, during fermentation. Because it is known that these compounds
      contribute to microbial growth and to changes in the constituent profile by
      altering the moromi environment, understanding the influence of these compounds
      is important. Metabolomics, the comprehensive study of low molecular weight
      metabolites, is a promising strategy for the deep understanding of constituent
      contributions to food characteristics. Therefore, the influences of microbes and
      their products such as lactic acid, acetic acid, and ethanol on aroma profiles
      were investigated using gas chromatography/mass spectrometry (GC/MS)-based
      metabolic profiling. The presence of aroma constituents influenced by microbes
      and chemically influenced by lactic acid, acetic acid, and ethanol were proposed.
      Most of the aroma constituents were not produced by adding ethanol alone,
      confirming the participation of yeast in aroma production. It was suggested that
      lactic acid bacterium relates to a key aromatic compound, 2,5-dimethyl-4-hydroxy
      3(2H)-furanone. However, most of the measured aroma constituents changed
      similarly in both samples with lactic acid bacterium and acids. Thus, it was
      clear that the effect of lactic acid and acetic acid on the aroma profile was
      significant.

PMID- 29366720
TI  - Comparative study of the impact of the administration of Amoxicillin and Algo
      Bio(r) alternative substance to antibiotics, on the level of selection of
      resistant Enterobacteriaceae in the digestive flora of piglets.
AB  - OBJECTIVES: The aim of study was to evaluate by comparative study the level of
      selection of antibiotic-resistant Enterobacteriaceae in the digestive microbiota
      of piglets when using amoxicillin and Algo-Bio(r). METHODS: Amoxicillin and Algo
      Bio(r) administration was carried out over a period of 5 days (D0-D4) at a dose
      of 1mL/10kg body weight. A phenotypic study was carried out with enumeration of
      resistant Enterobacteriaceae on MacConkey agar plates in the presence and absence
      of amoxicillin. Escherichia coli isolates were identified and were subjected to
      antimicrobial susceptibility testing. RESULTS: The percentages of amoxicillin
      resistant Enterobacteriaceae before treatment ranged from 10-15% for the four
      groups of piglets. Following treatment initiation, on the second day (D1) to the
      fifth day (D4) of treatment, the percentages increased to 54-87% for the groups
      treated with amoxicillin. In the group treated with Algo-Bio(r) and the controls,
      the percentages were <50%. The percentage of amoxicillin-resistant E. coli
      strains to the associated antibiotics increased during days of amoxicillin
      treatment, whereas in the control and Algo-Bio(r) groups the percentages of E.
      coli resistant to antibiotics did not increase. CONCLUSION: The results indicated
      that Algo-Bio(r) constitutes a good alternative prophylactic to antibiotics to
      reduce bacterial growth in the digestive tract of animals.

PMID- 29366721
TI  - Vibrio cholerae O1 gaining reduced susceptibility to doxycycline, India.

PMID- 29366722
TI  - Antibiotic resistance and breastfeeding: A neglected area of study.

PMID- 29366723
TI  - Clinical experience with ceftolozane/tazobactam in patients with serious
      infections due to resistant Pseudomonas aeruginosa.
AB  - OBJECTIVES: The incidence of infections caused by multidrug-resistant Pseudomonas
      aeruginosa (MDR-Pa) has become a concern of increasing relevance nowadays.
      Ceftolozane/tazobactam (C/T) is a novel fifth-generation cephalosporin/beta
      lactamase inhibitor combination with activity against MDR-Pa. METHODS: The
      clinical records of all patients diagnosed from May 2016 to May 2017 with an
      infection due to a MDR-Pa treated with C/T were retrospectively reviewed.
      RESULTS: A total of 23 patients with 24 episodes of infection due to MDR-Pa were
      included. The minimum inhibitory concentration (MIC) of C/T against MDR-Pa ranged
      from 0.75-8MUg/mL. In 14 cases (58%) the use of C/T was off-label, including 8
      respiratory tract infections (RTIs) and 6 skin and soft-tissue infections, whilst
      in 10 cases the use was for approved indications, including 7 urinary tract
      infections and 3 intra-abdominal infections. C/T was the first-line therapy in
      only three cases with a mean+/-standard deviation treatment duration of 9.3+/-4
      days, and it was associated with another active drug (aminoglycoside or colistin)
      in 16 cases. The global clinical cure rate was 88% (21/24 episodes), and the 6
      week mortality rate was 22% (5/23 patients) being higher in RTIs (37%). In these
      infections, three patients received 2/1g every 8h (q8h) and were cured without
      mortality, whilst three (60%) of five patients receiving 1/0.5g q8h died.
      CONCLUSION: C/T had good clinical responses in different types of infection,
      including both FDA-accepted and off-label indications. The results support the
      use of higher doses in RTIs.

PMID- 29366725
TI  - Performance of the 2012 Systemic Lupus International Collaborating Clinics
      classification criteria versus the 1997 American College of Rheumatology
      classification criteria in adult and juvenile systemic lupus erythematosus. A
      systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the performance in classifying systemic lupus
      erythematosus by the 2012 Systemic Lupus International Collaborating Clinics
      criteria (SLICC'12), versus the revised American College of Rheumatology criteria
      from 1997 (ACR'97) in adult and juvenile SLE patients. METHODS: A systematic
      literature search was conducted in PubMed and Embase for studies comparing
      SLICC'12 and ACR'97 with clinical diagnosis. A meta-analysis was performed to
      estimate the sensitivity and specificity of SLICC'12 and ACR'97. To assess
      classification earlier in the disease by either set, sensitivity and specificity
      were compared for patients with disease duration <5years. Sensitivity and
      specificity of individual criteria items were also assessed. RESULTS: In adult
      SLE (nine studies: 5236 patients, 1313 controls), SLICC'12 has higher sensitivity
      (94.6% vs. 89.6%) and similar specificity (95.5% vs. 98.1%) compared to ACR'97.
      For juvenile SLE (four studies: 568 patients, 339 controls), SLICC'12
      demonstrates higher sensitivity (99.9% vs. 84.3%) than ACR'97, but much lower
      specificity (82.0% vs. 94.1%). SLICC'12 classifies juvenile SLE patients earlier
      in disease course. Individual items contributing to diagnostic accuracy are low
      complement, anti-ds DNA and acute cutaneous lupus in SLICC'12, and the
      immunologic and hematologic disorder in ACR'97. CONCLUSION: Based on sensitivity
      and specificity SLICC'12 is best for adult SLE. Following the view that higher
      specificity, i.e. avoidance of false positives, is preferable, ACR'97 is best for
      juvenile SLE even if associated with lower sensitivity. Our results on the
      contribution of the individual items of SLICC'12 and ACR'97 may be of value in
      future efforts to update classification criteria.

PMID- 29366724
TI  - Effects of Community-Based Exercise in Adults With Severe Burns: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To investigate the efficacy of community-based exercise programs in
      the rehabilitation of adult patients with burns compared with standard of care
      (SOC). DESIGN: Randomized controlled trial, with 2:1 randomization. SETTING:
      Assessments were performed in a hospital setting. The intervention was performed
      in a community setting. PARTICIPANTS: Adult patients (N=45) with >=30% total body
      surface area burns were randomized to participate in a community-based exercise
      program (n=31) or SOC (n=14). Patient sampling was consecutive and referred.
      INTERVENTIONS: The community-based exercise program consisted of 12 weeks of
      exercise with a community-based trainer after hospital discharge. The SOC group
      did not receive exercise training. MAIN OUTCOME MEASURES: Change in lean body
      mass index, peak torque, and peak oxygen consumption from discharge to 12 weeks
      postdischarge, presented as mean +/- SE. RESULTS: The community-based exercise
      program group showed a significant increase in peak oxygen consumption compared
      with SOC (community-based exercise program: Delta=7.723+/-1.522mL/kg/min,
      P=.0006; SOC: Delta=2.200+/-1.150mL/kg/min, P=.0765; community-based exercise
      program vs SOC, P=.0236). The community-based exercise program group exhibited a
      significant within group increase in lean body mass index (Delta=1.107+/
      0.431kg/m2, P=.0003; SOC: Delta=1.323+/-0.873kg/m2, P=.2808). Both groups showed
      significant within-group increases in peak torque (community-based exercise
      program: Delta=35.645+/-7.566Nm, P=.0003; SOC: Delta=34.717+/-11.029Nm, P=.0082).
      No significant differences were noted between the 2 groups for lean body mass
      index or peak torque. CONCLUSIONS: Patients who participate in a community-based
      exercise program show significant improvements in cardiopulmonary fitness
      compared with SOC, supporting the use of a community-based exercise program as an
      alternative therapy to SOC in adults with severe burns.

PMID- 29366726
TI  - Use of an Artificial Ligament Decreases Hip Dislocation and Improves Limb
      Function After Total Femoral Prosthetic Replacement Following Femoral Tumor
      Resection.
AB  - BACKGROUND: Hip dislocation is a major complication of total femoral prosthetic
      reconstruction (TFR) after femoral tumor resection. Hip dislocation can occur
      because of inadequate functional abductor musculature, inadequate hip capsule
      repair, or a long lever arm after total femur replacement. To eliminate the
      negative effects of these factors on the risk of hip dislocation, the use of
      artificial ligaments may help to increase the stability of the hip joint. We
      aimed to determine whether application of an artificial ligament would improve
      limb function and active range of movement (ROM) after TFR. METHODS: Fifty-eight
      patients who underwent femoral tumor resection and TFR were included. A band
      shaped artificial ligament was wrapped spirally around the proximal site of the
      total femur prosthesis for periacetabular soft tissue reconstruction in 12
      patients. The other 46 patients did not consent to receiving the artificial
      ligament. Complications including hip dislocation and infection, limb function,
      and active hip ROM were compared between patients who did and did not receive the
      artificial ligament. RESULTS: The hip dislocation rate was lower in the patients
      who received the artificial ligament. The risk of deep infection did not differ
      between groups. The group that received the ligament also achieved better limb
      function and active ROM on flexion and abduction. CONCLUSION: Patients treated
      with total femur resection and endoprosthetic replacement with an artificial
      ligament for periacetabular soft tissue reconstruction had a more stable hip
      joint, better limb function, and greater active hip ROM than did patients who did
      not receive an artificial ligament.

PMID- 29366727
TI  - Response to the Letter to the Editor on "Serum and Wound Vancomycin Levels
      Following Intrawound Administration in Primary Total Joint Arthroplasty".

PMID- 29366728
TI  - Bariatric Surgery Improves Outcomes After Lower Extremity Arthroplasty in the
      Morbidly Obese: A Propensity Score-Matched Analysis of a New York Statewide
      Database.
AB  - BACKGROUND: The purpose of this study was to compare risks for revision and short
      term complications after total joint arthroplasty (TJA) in matched cohorts of
      morbidly obese patients, receiving and not receiving prior bariatric surgery.
      METHODS: Patients undergoing elective TJA between 1997 and 2011 were identified
      in a New York Statewide database, analyzing total knee arthroplasty (TKA) and
      total hip arthroplasty (THA) separately. Propensity scores were used to match
      morbidly obese patients receiving and not receiving bariatric surgery prior to
      TJA. Cox proportional hazard modeling assessed revision risk. Logistic regression
      evaluated odds for complications. RESULTS: For TKA, 2636 bariatric surgery
      patients were matched to 2636 morbidly obese patients. For THA, 792 bariatric
      surgery patients were matched to 792 morbidly obese patients. Matching balanced
      all covariates. Bariatric surgery reduced co-morbidities prior to TJA (TKA P <
      .0001; THA P < .005). Risks for in-hospital complications were lower for THA and
      TKA patients receiving prior bariatric surgery (odds ratio [OR] 0.25, P < .001;
      and OR = 0.69, P = .021, respectively). Risks for 90-day complications were lower
      for TKA (OR 0.61, P = .002). Revision risks were not different for either THA (P
      = .634) or TKA (P = .431), nor was THA dislocation risk (P = 1.000). CONCLUSION:
      After accounting for relevant selection biases, bariatric surgery prior to TJA
      was associated with reduced co-morbidity burden at the time of TJA and with
      reduced post-TJA complications. However, bariatric surgery did not reduce the
      risk for revision surgery for either TKA or THA.

PMID- 29366729
TI  - Accuracy of Digital Tomosynthesis With Metal Artifact Reduction for Detecting
      Osteointegration in Cementless Hip Arthroplasty.
AB  - BACKGROUND: Cementless hip arthroplasty is increasingly gaining popularity
      worldwide. Radiologic identification of osteointegration is key to confirming
      biologic fixation. We conducted the study reported here to determine the
      sensitivity and specificity of digital tomosynthesis with metal artifact
      reduction (TMAR), radiography, and conventional computed tomography in detecting
      osteointegration in cementless hip arthroplasty. METHODS: We prospectively
      included data for 24 patients who underwent revision hip arthroplasty in our
      hospital, with 13 femoral and 14 acetabular cementless components retrieved that
      contained solid evidence of biologic fixation. All patients underwent 3
      examinations before surgery, and evidence of osteointegration on retrieved
      prostheses was used as the reference standard. Seven orthopedic surgeons
      evaluated these images independently using uniform criteria. RESULTS: On the
      femoral side, the sensitivity and specificity of detecting osteointegration were
      73.8% +/- 4.6% and 94.3% +/- 1.5%, respectively, for TMAR; 50.4% +/- 5.3% and
      87.8% +/- 2.1%, respectively, for radiography; and 36.4% +/- 5.1% and 90.9% +/-
      1.9%, respectively, for CT. On the cup side, the corresponding values were 60.2%
      +/- 8.3% and 86.4% +/- 5.7%, respectively, for TMAR; 45.9% +/- 8.5% and 66.4% +/-
      7.8%, respectively, for radiography; and 45.1% +/- 8.5% and 73.5% +/- 7.3%,
      respectively, by computed tomography. CONCLUSION: TMAR significantly improved the
      accuracy osteointegration detection in cementless hip arthroplasty (P < .017).

PMID- 29366730
TI  - Preoperative Canal Bone Ratio is Related to High-Degree Stress Shielding: A
      Minimum 5-Year Follow-Up Study of a Proximally Hydroxyapatite-Coated Straight
      Tapered Titanium Femoral Component.
AB  - BACKGROUND: Few studies have reported risk factors for stress shielding. We
      sought to evaluate clinical and radiographic outcomes of a proximally
      hydroxyapatite-coated straight tapered titanium femoral component stem during a
      minimum 5-year follow-up and identify factors associated with high-degree stress
      shielding. METHODS: A total of 156 total hip arthroplasties (n = 124; 98 women
      and 26 men; mean age, 56.5 years) with a minimum follow-up period of 5 years were
      included in the study. Clinical and radiologic measurements at follow-up (range,
      5-16.3 years; mean, 10.2 years) were analyzed. RESULTS: The mean preoperative
      Harris Hip Score (HHS) was 56.6, and the mean HHS at the latest follow-up was
      considerably improved at 86.8. Stress shielding at the latest follow-up was low
      degree in 136 (87%) hips and high degree in 20 (13%) hips. On average, high
      degree stress shielding occurred 9.9 years (5-14 years) after surgery. The
      results of Cox proportional hazard analysis showed that a canal bone ratio >=
      0.49 was an independent risk factor for high-degree stress shielding (P = .0075;
      hazard ratio, 3.981). HHS at the latest follow-up was significantly lower in high
      degree stress shielding than in low-degree stress shielding (80.7 and 87.7,
      respectively; P = .0030). CONCLUSION: Preoperative canal bone ratio >= 0.49 is
      independently associated with high-degree stress shielding. In addition, the
      number of cases with high-degree stress shielding significantly increased over
      time during a mean 10-year follow-up.

PMID- 29366731
TI  - Acute interruption of treatment with nandrolone decanoate is not sufficient to
      reverse cardiac autonomic dysfunction and ventricular repolarization disturbances
      in rats.
AB  - Anabolic androgenic steroids are a class of synthetic compounds derived from
      testosterone, eventually used by athletes, to improve physical performance.
      However, anabolic steroids can also modify normal cardiovascular function. Thus,
      we investigated cardiac electrophysiological and autonomic abnormalities in rats,
      through a electrocardiographic variability protocol during and after interruption
      of administration of nandrolone decanoate (DECA) anabolic steroid. Twenty male
      Wistar rats (60-70 days old) received DECA (10 mg. kg-1i.m) once a week or
      vehicle, during eight weeks. Electrocardiogram was recorded in conscious rats by
      a noninvasive method, and time and domain analysis of heart rate variability as
      well as electrocardiogram intervals (QTc / QTd) were performed. Body mass was
      lower in treated rats compared to control after 4th and 8th weeks, but not at the
      end of 14th week. QTc and QTd were longer in DECA group compared to control on
      4th, 8th, 11th, but equal on 14th week. Cardiac autonomic dysfunction (vagal
      attenuation) was present on DECA group after 4th week and did not normalize after
      interruption of treatment. The animals of DECA group showed a correlation between
      attenuated parasympathetic modulation and increased correct QT interval. Our data
      allow us to conclude that long-term treatment with DECA impairs autonomic cardiac
      physiology, predisposing to cardiovascular risk and sudden death, and
      interruption of administration does not recovery the normality immediately.

PMID- 29366732
TI  - Allergy and mental health among pregnant women in the Japan Environment and
      Children's Study.

PMID- 29366733
TI  - Improved glycemic control with once-weekly dulaglutide in addition to insulin
      therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by
      continuous glucose monitoring.
AB  - AIMS: To evaluate the efficacy and safety of adding once-weekly dulaglutide to
      insulin therapy in type 2 diabetes mellitus (T2DM) patients on hemodialysis.
      METHODS: Fifteen insulin-treated T2DM patients on hemodialysis were enrolled.
      Continuous glucose monitoring was performed before (1st hospitalization) and
      after the fifth dulaglutide administration (2nd hospitalization). The insulin
      dose was reduced after the first administration of dulaglutide (1st
      hospitalization day 6). Parameters of glycemic control were compared on 1st
      hospitalization days 4-5, 2nd hospitalization days 3-4, and days 6-7. RESULTS:
      The median total daily insulin dose was reduced significantly from 12 (12-25) to
      0 (0-12) U (p < 0.0001) after treatment with dulaglutide. Mean glucose level on
      2nd hospitalization days 3-4 significantly decreased and that on days 6-7 tended
      to decrease compared with that on 1st hospitalization days 4-5 (median, 8.2 to
      6.7 mmol/L, P = 0.006 and 8.2 to 6.9 mmol/L, P = 0.053, respectively). %CV of
      glucose levels decreased significantly after dulaglutide administration (28.1 to
      19.8, P = 0.003 and 28.1 to 21.0, P = 0.019). However, the incidence of
      hypoglycemia remained unchanged. CONCLUSIONS: Dulaglutide may improve glycemic
      control and excursion and allow total daily insulin to be reduced without
      increasing the risk of hypoglycemia in T2DM patients on hemodialysis.

PMID- 29366734
TI  - Left ventricular systolic dysfunction predicts long-term major microvascular
      complication outcomes in type 1 diabetes. The Pittsburgh Epidemiology of Diabetes
      Complications (EDC) study of childhood onset diabetes.
AB  - OBJECTIVES: We aimed to assess association between abnormal LVEF, in the absence
      of coronary artery disease (CAD), and 25-year incidence of major outcomes of
      diabetes (MOD) in a cardiology substudy of the Pittsburgh Epidemiology of
      Diabetes Complications cohort of childhood-onset type 1 diabetes. METHODS: 115
      normotensive type 1 diabetes individuals without known CAD, underwent a baseline
      exercise radionuclide ventriculography. Abnormal LVEF was defined as a resting
      ejection fraction <50% or a failure to increase ejection fraction with exercise
      by >5% (men) or a fall in ejection fraction with exercise (women). Cox
      proportional hazards models were used to predict the composite endpoint of MOD
      (first instance of major CAD, stroke, end-stage renal disease, blindness,
      amputation or diabetes-related death). RESULTS: Mean baseline age was 28 and
      diabetes duration 19 years. In a mean follow-up of 19 years, 50 MOD events were
      identified. Allowing for established risk factors at baseline, abnormal LVEF (n =
      22) independently predicted MOD incidence (HR = 2.12, 95% CI: 1.12-4.00, p =
      0.022) but not major CAD (HR = 1.33, 95% CI: 0.53-3.33, p = 0.539). CONCLUSIONS:
      An abnormal LVEF may identify diabetic cardiomyopathy and predict long term risk
      of MOD (but not CAD alone) in type 1 diabetes individuals, consistent with it
      reflecting microvascular disease.

PMID- 29366735
TI  - New 1,3-benzodioxole derivatives: Synthesis, evaluation of in vitro
      schistosomicidal activity and ultrastructural analysis.
AB  - Schistosomiasis is considered a serious public health problem in 78 countries and
      territories located in Africa, Asia and America and it is estimated in more than
      249 million people infected by any of the species of Schistosoma. The exclusive
      use of praziquantel (PZQ), effective drug against all species of Schistosoma, has
      been the basis of the development of a possible resistance against the strains of
      this parasite. In addition, PZQ is not effective against young forms of worms.
      Thus, there is a need for the development of new drugs with schistosomicidal
      activity. The objective of this work was to synthesize and to evaluate the
      therapeutic potential of new benzodioxole derivatives (3-14) candidates for
      schistosomicidal drugs. All compounds synthesized showed in vitro
      schistosomicidal activity. The derivative 12 was considered the best compound,
      since it took 100% of worms to mortality in the first 72 h of exposure at the
      concentration of 100 MUM and 83.3% at the concentration of 50 MUM. Furthermore,
      male and female adult worms, incubated for 24 h with the compound 12 showed
      tegument damages characterized by extensive desquamation and edema, tuber
      destruction, bubble formation and exposure of the muscle layer. This compound has
      a restricted structure, where the thiazolidinone is attached to the 4-position of
      the 1,3-benzodioxol ring. The structural conformation of derivative 12 was
      probably responsible for the promising schistosomicidal activity, where the
      presence of an electron/conformational restriction of the thiazolidine ring, as
      well as the action of bromine as a bulk substitute, favored an increase in
      biological activity. In addition, tegumentary changes caused by derivative 12 may
      also have been responsible for the death of adult worms of Schistosoma mansoni.
      Therefore, we verified that the results obtained in this study make benzodioxole
      derivatives possible candidates for prototypes of new schistosomicidal drugs.

PMID- 29366736
TI  - Epidemiologist's view: Addressing the epilepsy surgery treatment gap with
      minimally-invasive techniques.
AB  - Despite the fact that epilepsy surgery is both safe and effective, a considerable
      "surgical treatment gap" remains in that most persons who are eligible for
      surgery do not receive it. It has been argued that epilepsy surgery is one of the
      most underutilized of all accepted medical treatments in the world. In this
      article, we review the epidemiology of the epilepsy surgery treatment gap, and
      consider the role minimally-invasive epilepsy surgery may play in reducing this
      gap.

PMID- 29366737
TI  - On the quantitative phase analysis and amorphous content of triacylglycerols
      materials by X-ray Rietveld method.
AB  - The characterization of fat components becomes very useful for formulation of
      shortening, margarines and fat products due to their unique properties of
      plasticity, texture, solubility, and aeration. However, X-ray diffraction
      experiments on such materials are usually limited to a qualitative evaluation of
      the polymorphic properties based only on the characteristic d-spacing peak
      intensities. In this work, interesting results based on the Rietveld Method have
      supported both a Quantitative Phase Analysis and Degree of Crystallinity study on
      industrial and academic appealing samples, such as triacylglycerol standards,
      fully hydrogenated vegetable oils (hardfats) and cocoa butter. This useful
      approach to the area of oils and fats can provide valuable information about the
      polymorphism and its relationship to the application of lipid materials in food
      science and technology. Here, the discrimination between beta and beta'
      polymorphs on samples made of mixtures or blended hardfats was attained, and the
      results have shown a relevant contrast in comparison to a purely qualitative
      approach. Assessment of amorphous content on cocoa butter samples was achieved by
      isolating its contribution from the total X-ray diffraction background via
      mathematical tools during the whole pattern fitting.

PMID- 29366738
TI  - Could age and aging change the host response to systemic parasitic infections? A
      systematic review of preclinical evidence.
AB  - The impact of age and aging in the evolution of systemic parasitic infections
      remains poorly understood. We conducted a systematic review from preclinical
      models of Chagas disease, leishmaniasis, malaria, sleeping sickness and
      toxoplasmosis. From a structured and comprehensive search in electronic
      databases, 29 studies were recovered and included in the review. Beyond the
      characteristics of the experimental models, parasitological and immunological
      outcomes, we also discussed the quality of current evidence. Our findings
      indicated that throughout aging, parasitemia and mortality were consistently
      reduced in Chagas disease and malaria, but were similar or increased in
      leishmaniasis and highly variable in toxoplasmosis. While a marked humoral
      response in older animals was related to the anti-T. cruzi protective phenotype,
      cellular responses mediated by a polarized Th1 phenotype were associated with a
      more effective defense against Plasmodium infection. Conversely, in
      leishmaniasis, severe infections and high mortality rates were potentially
      related to attenuation of humoral response and an imbalance between Th1 and Th2
      phenotypes. Due to the heterogeneous parasitological outcomes and limited
      immunological data, the role of aging on toxoplasmosis evolution remains unclear.
      From a detailed description of the methodological bias, more controlled
      researches could avoid the systematic reproduction of inconsistent and poorly
      reproducible experimental designs.

PMID- 29366739
TI  - A Comparison of Radiofrequency-Based Microtenotomy and Arthroscopic Release of
      the Extensor Carpi Radialis Brevis Tendon in Recalcitrant Lateral Epicondylitis:
      A Prospective Randomized Controlled Study.
AB  - PURPOSE: To compare the clinical effects of radiofrequency (RF)-based
      microtenotomy and arthroscopic release of the extensor carpi radialis brevis
      (ECRB) tendon in patients with recalcitrant lateral epicondylitis through a
      prospective randomized controlled study. METHODS: A total of 46 patients were
      randomly assigned to receive arthroscopic release (group A, 24 patients) or RF
      based microtenotomy (group B, 22 patients). The visual analog scale (VAS) score
      for pain, flexion-extension arc, operation time, Disabilities of the Arm,
      Shoulder, and Hand questionnaire (DASH), Mayo Elbow Performance Score (MEPS), and
      grip power of groups A and B were compared during the recovery phases for up to 2
      postoperative years. RESULTS: Both groups showed statistically significant
      functional improvement compared with their preoperative grip strength and DASH,
      VAS, and MEPS scores at 2 years after surgery (P < .05). There were no
      differences in postoperative pain relief or functional restoration between the 2
      groups during the recovery phases, however the mean operation time for group B
      (41.4 +/- 5.2 minutes) was significantly shorter than that for group A (15.6 +/-
      3.6 minutes, P < .001). In group B, 1 patient underwent revision surgery due to
      postoperative ECRB rupture, and 1 patient in group A underwent open release for
      persistent postoperative discomfort. CONCLUSIONS: RF-based microtenotomy for
      treating recalcitrant lateral epicondylitis provided clinical outcomes comparable
      with those from arthroscopic release of ECRB tendon during the recovery phase. RF
      based microtenotomy is considered as one of the surgical procedures for treating
      recalcitrant lateral epicondylitis, with the advantages of reliable elbow
      functional restoration and significantly shorter operation time. LEVEL OF
      EVIDENCE: Level I, prospective randomized trial.

PMID- 29366740
TI  - Knee Osteoarthritis After Anterior Cruciate Ligament Reconstruction With Bone
      Patellar Tendon-Bone Versus Hamstring Tendon Autograft: A Systematic Review of
      Randomized Controlled Trials.
AB  - PURPOSE: The primary purpose of this study was to systematically review high
      quality studies in the literature to compare the postoperative radiographic
      incidence of knee osteoarthritis (OA) after anterior cruciate ligament
      reconstruction (ACLR) with bone-patellar tendon-bone (BPTB) versus hamstring
      tendon (HT) autograft. The secondary purpose of this study was to compare other
      symptoms of postoperative knee OA between these 2 groups through patient-reported
      outcome scores and knee range of motion. METHODS: A systematic review was
      performed by searching PubMed, Embase, and Cochrane Library to locate randomized
      controlled trials that compared postoperative progression of knee OA in patients
      who had undergone ACLR with BPTB versus HT autograft. Search terms used were
      "anterior cruciate ligament reconstruction," "patellar tendon," "hamstring,"
      "randomized," and "osteoarthritis." Patients were assessed based on radiographic
      evaluation (Kellgren-Lawrence, Ahlback, Fairbank, and the Objective International
      Knee Documentation Committee scales), patient-reported outcome scores (Knee
      Injury and Osteoarthritis Outcome Score and visual analog scale scores), graft
      failure, and active knee flexion and extension deficit. RESULTS: Eight studies (6
      Level I, 2 Level II) were identified that met inclusion criteria, including a
      total of 237 and 268 nonoverlapping patients who had undergone ACLR with BPTB and
      HT autograft, respectively, with a mean follow-up of 11.5 years (range, 3-16
      years). Graft failure was experienced by 7.0% of patients in each group (P =
      .99). A Kellgren-Lawrence grade >=2 was found in 52.0% and 51.0% of BPTB and HT
      autograft patients, respectively (P = .85). An Ahlback and Fairbank grade >=2 was
      found in 5.0% and 8.4% of BPTB and HT autograft patients, respectively (P = .36).
      There were no significant differences in any patient-reported outcomes between
      groups within any study. CONCLUSIONS: Patients undergoing ACLR with BPTB
      autograft or HT autograft can be expected to experience a similar incidence of
      postoperative knee OA at long-term follow-up. LEVEL OF EVIDENCE: Level II,
      systematic review of Level I and II studies.

PMID- 29366741
TI  - Graft Choice in Isolated Medial Patellofemoral Ligament Reconstruction: A
      Systematic Review With Meta-analysis of Rates of Recurrent Instability and
      Patient-Reported Outcomes for Autograft, Allograft, and Synthetic Options.
AB  - PURPOSE: To determine whether graft selection or patient age affects the
      following after isolated medial patellofemoral ligament (MPFL) reconstruction:
      (1) rates of recurrent instability, (2) rates of postoperative complications
      (other than instability), and (3) subjective symptom improvement. METHODS: A
      systematic search identified studies reporting outcomes for isolated MPFL
      reconstruction. Rates of recurrent instability, subjective Kujala knee function
      scores, and complications were tabulated. Symptom improvement was defined as
      change in Kujala score (preoperative evaluation to final follow-up). RESULTS:
      Forty-five studies were included with 27 documented cases of recurrent
      instability among 1,504 patients (1.8%); instability rates ranged from 0% to
      20.0% overall; among autograft in adults, 0% to 11.1% (1.4%, 18/1,260); among
      autograft in adolescents, 0% to 20% (10.0%, 8/80); among allograft, 0% (0/65
      cases); and among synthetic, 0% to 3.3% (1.3%, 1/76). Among autograft choices in
      adults, rates of recurrent instability were low; recurrence with gracilis ranged
      from 0% to 11.1% (0.9%, 1/116); with semitendinosus, 0% to 6.3% (0.6%, 4/676);
      with quad or patellar tendon, 0% (0/65); and with adductor tendon, 5.6% to 8.3%
      (6.7%, 2/30). Complication rates ranged from 0% to 34.4%. All included studies
      reported significant improvement in Kujala scores after surgery (P < .01). There
      was significant heterogeneity in effect size and evidence of reporting bias among
      small studies, precluding reliable pooled analysis of treatment effect.
      CONCLUSIONS: Autograft is not superior to allograft or synthetic grafts for
      isolated reconstruction of the MPFL, and rates of recurrent instability are
      generally low. Isolated MPFL reconstruction can provide significant symptom
      relief regardless of graft selection, although there is a bias toward reporting
      better than expected results among smaller studies. Pediatric patients and
      patients treated with adductor tendon autograft have higher recurrent instability
      rates. While caution should be used in making definitive recommendations
      secondary to the small number of allograft and synthetic studies, selection of
      graft type based on surgeon preference, comfort, and prior experience remains
      appropriate. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV
      studies.

PMID- 29366742
TI  - Utility of Modern Arthroscopic Simulator Training Models: A Meta-analysis and
      Updated Systematic Review.
AB  - PURPOSE: To determine the utility of modern arthroscopic simulators in
      transferring skills learned on the model to the operating room. METHODS: A meta
      analysis and systematic review of all English-language studies relevant to
      validated arthroscopic simulation models using PRISMA (Preferred Reporting Items
      for Systematic Reviews and Meta-analyses) guidelines from 1999 to 2016 was
      performed. Data collected included the specific simulator model, the joint used,
      participant demographic characteristics, participant level of training, training
      session information, type and number of tasks, pre- and post-training
      assessments, and overall outcomes of simulator performance. Three independent
      reviewers analyzed all studies. RESULTS: Fifty-seven studies with 1,698
      participants met the study criteria and were included. Of the studies, 25 (44%)
      incorporated an arthroscopic training program into the study methods whereas 32
      (56%) did not. In 46 studies (81%), the studies' respective simulator models were
      used to assess arthroscopic performance, whereas 9 studies (16%) used Sawbones
      models, 8 (14%) used cadaveric models, and 4 (7%) evaluated subject performance
      on a live patient in the operating room. In 21 studies (37%), simulator
      performance was compared with experience level, with 20 of these (95%) showing
      that clinical experience correlated with simulator performance. In 25 studies
      (44%), task performance was evaluated before and after simulator training, with
      24 of these (96%) showing improvement after training. All 4 studies that included
      live-patient arthroscopy reported improved operating room performance after
      simulator training compared with the performance of subjects not participating in
      a training program. CONCLUSIONS: This review suggests that (1) training on
      arthroscopic simulators improves performance on arthroscopic simulators and (2)
      performance on simulators for basic diagnostic arthroscopy correlates with
      experience level. Limited data suggest that simulator training can improve basic
      diagnostic arthroscopy skills in vivo. LEVEL OF EVIDENCE: Level IV, systematic
      review of Level I through IV studies.

PMID- 29366743
TI  - Comparison of Tibiofemoral Contact Mechanics After Various Transtibial and All
      Inside Fixation Techniques for Medial Meniscus Posterior Root Radial Tears in a
      Porcine Model.
AB  - PURPOSE: To compare tibiofemoral contact mechanics after fixation for medial
      meniscus posterior root radial tears (MMPRTs). METHODS: Seven fresh knees from
      mature pigs were used. Each knee was tested under 5 conditions: normal knee,
      MMPRT, pullout fixation with simple sutures, fixation with modified Mason-Allen
      sutures, and all-inside fixation using Fastfix 360. The peak contact pressure and
      contact surface area were evaluated using a capacitive sensor positioned between
      the meniscus and tibial plateau, under a 1,000-N compression force, at different
      flexion angles (0 degrees , 30 degrees , 60 degrees , and 90 degrees ). RESULTS:
      The peak contact pressure was significantly higher in MMPRTs than in normal knees
      (P = .018). Although the peak contact pressure decreased significantly after
      fixation at all flexion angles (P = .031), it never recovered to the values noted
      in the normal meniscus. No difference was observed among fixation groups (P =
      .054). The contact surface area was significantly lower in MMPRTs than in the
      normal meniscus (P = .018) and increased significantly after fixation at all
      flexion angles (P = .018) but did not recover to within normal limits. For all
      flexion angles except 60 degrees , the contact surface area was significantly
      higher for fixation with Mason-Allen sutures than for fixation with simple
      sutures or all-inside fixation (P = .027). At 90 degrees  of flexion, the contact
      surface area was significantly better for fixation with simple sutures than for
      all-inside fixation (P = .031). CONCLUSIONS: The peak contact pressure and
      contact surface area improved significantly after fixation, regardless of the
      fixation method, but did not recover to the levels noted in the normal meniscus
      after any type of fixation. Among the fixation methods evaluated in this time 0
      study, fixation using modified Mason-Allen sutures provided a superior contact
      surface area compared with that noted after fixation using simple sutures or all
      inside fixation, except at 60 degrees  of flexion. However, this study had
      insufficient power to accurately detect the differences between the outcomes of
      various fixation methods. CLINICAL RELEVANCE: Our results in a porcine model
      suggest that fixation can restore tibiofemoral contact mechanics in MMPRT and
      that fixation with a locking mechanism leads to superior biomechanical
      properties.

PMID- 29366744
TI  - Growth Factors Levels Determine Efficacy of Platelets Rich Plasma Injection in
      Knee Osteoarthritis: A Randomized Double Blind Noninferiority Trial Compared With
      Viscosupplementation.
AB  - PURPOSE: To assess the noninferiority of a single platelet-rich plasma (PRP)
      injection compared with hyaluronic acid (HA), to alleviate pain and enhance
      functional capacity in knee osteoarthritis, and identify biological
      characteristics of PRP that may affect their efficacy. METHODS: Fifty-four
      patients with symptomatic knee osteoarthritis received a single injection of
      either PRP (26 patients) or HA (28 patients). They were assessed at baseline and
      at 1, 3, and 6 months. The primary endpoint was the change in Western Ontario and
      McMaster Universities Arthritis Index (WOMAC) score at 3 months, and secondary
      endpoints were responders' rate (improvement of at least 5 points or 40% of WOMAC
      total score at 3 months) of pain evaluation and patient's subjective
      satisfaction. Cell counts and the contents of vascular endothelial growth factor
      (VEGF), platelet-derived growth factor-AB (PDGF-AB), transforming growth factor
      beta 1 (TGF-beta1) content of injected PRP were assessed to analyze their
      relationship with clinical outcome. RESULTS: Both treatments proved their
      improvement in knee functional status and symptom relief, with a significant
      decrease observed at 1 month on all scores except for pain VAS in PRP group and
      WOMAC function score in the HA group. No difference between groups regarding
      WOMAC and VAS scores was observed. A higher percentage of responders was observed
      in the PRP group (72.7%) than in the HA group (45.8%) without significance (P =
      .064). The quantity of injected PDGF-AB and TGF-beta1 correlated with the change
      in WOMAC scores at 3 months and was lower in responders than in nonresponders (P
      = .009 and P = .003, respectively). CONCLUSIONS: Current results indicated that a
      single injection of very pure PRP offers a significant clinical improvement in
      the management of knee osteoarthritis, equivalent to a single HA injection in
      this patient population. Moreover, a significant correlation between the doses of
      TGF-beta1 and PDGF-AB and the worsening of WOMAC score 3 months after the
      procedure was found. LEVEL OF EVIDENCE: Level II, randomized double blind
      controlled trial.

PMID- 29366745
TI  - Glycyrrhizic acid ameliorates the kynurenine pathway in association with its
      antidepressant effect.
AB  - Our previous study implied the role of central high mobility group box 1 (HMGB1)
      in lipopolysaccharide (LPS)-induced depressive-like behaviors that could
      partially abrogate by glycyrrhizic acid (GZA). Here, we considered the potential
      mechanism underlying GZA ameliorating chronic stress-induced depression both in
      vivo and in vitro. Depression model was established with the 4-week chronic
      unpredictable mild stress (CUMS) mice. Sucrose preference test, tail suspension
      test and open field test were performed to reflect depressive-like behaviors.
      Enzyme activity of indoleamine-2,3-dioxygenase (IDO) was recorded with the ratio
      of kynurenine (KYN) / tryptophan (Trp). Transcription of gene was evaluated by RT
      PCR. Along with depressive-like behaviors, IDO, the rate-limiting enzyme of the
      kynurenine pathway (KP), was upregulated at the level of mRNA expression, and
      enzyme activity was also elevated in stressed hippocampi and LPS/HMGB1-treated
      hippocampus slices. Treatment of mice with GZA, the inhibitor of HMGB1, prevented
      the activated enzymes in KP and the development of depressive-like behaviors.
      These experiments demonstrate that GZA may restrain HMGB1 thus improving chronic
      stress-induced depressive behavior through regulating KP.

PMID- 29366746
TI  - How Cardiac Anesthesiology Can Help "STEM" the Tide of Under-representation of
      Minorities in Science and Medicine.
AB  - The field of medicine is built upon science, technology, engineering, and math
      (STEM), yet the United States is rapidly falling behind when it comes to
      educating the next generation in these disciplines, especially under-represented
      populations. The authors reflect on existing educational literature surrounding
      efforts to promote interest in STEM among students and under-represented
      populations. The authors advocate for greater efforts toward the development of
      youth programing. Cardiac anesthesia is uniquely positioned as a subspecialty to
      advance the goal of promoting interest in STEM in diverse groups of young
      students. The authors describe their development and implementation of a
      community outreach program to enhance interest in medicine through a cardiac
      dissection experience.

PMID- 29366747
TI  - Ghrelin potentiates cardiac reactivity to stress by modulating sympathetic
      control and beta-adrenergic response.
AB  - : Prior evidence indicates that ghrelin is involved in the integration of
      cardiovascular functions and behavioral responses. Ghrelin actions are mediated
      by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is
      expressed in peripheral tissues and central areas involved in the control of
      cardiovascular responses to stress. AIMS: In the present study, we assessed the
      role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute
      emotional stress in rats. MAIN METHODS AND KEY FINDINGS: Ghrelin potentiated the
      tachycardia evoked by restraint and air jet stresses, which was reverted by GHS
      R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic
      branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the
      perfusion with ghrelin potentiated the contractile responses caused by
      stimulation of the beta-adrenergic receptor, without altering the amplitude of
      the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes
      revealed that ghrelin amplified the increases in calcium transient changes evoked
      by isoproterenol. SIGNIFICANCE: Taken together, our results indicate that the
      Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by
      modulating the autonomic nervous system and peripheral mechanisms, strongly
      relying on the activation of cardiac calcium transient and beta-adrenergic
      receptors.

PMID- 29366748
TI  - Exercise training versus T3 and T4 hormones treatment: The differential benefits
      of thyroid hormones on the parasympathetic drive of infarcted rats.
AB  - AIMS: This study aimed to investigate whether beneficial effects of thyroid
      hormones are comparable to those provided by the aerobic exercise training, to
      verify its applicability as a therapeutic alternative to reverse the pathological
      cardiac remodeling post-infarction. MATERIALS AND METHODS: Male rats were divided
      into SHAM-operated (SHAM), myocardial infarction (MI), MI subjected to exercise
      training (MIE), and MI who received T3 and T4 treatment (MIH) (n = 8/group). MI,
      MIE and MIH groups underwent an infarction surgery while SHAM was SHAM-operated.
      One-week post-surgery, MIE and MIH groups started the exercise training protocol
      (moderate intensity on treadmill), or the T3 (1.2 MUg/100 g/day) and T4 (4.8
      MUg/100 g/day) hormones treatment by gavage, respectively, meanwhile SHAM and MI
      had no intervention for 9 weeks. The groups were accompanied until 74 days after
      surgery, when all animals were anesthetized, left ventricle echocardiography and
      femoral catheterization were performed, followed by euthanasia and left ventricle
      collection for morphological, oxidative stress, and intracellular kinases
      expression analysis. KEY FINDINGS: Thyroid hormones treatment was more effective
      in cardiac dilation and infarction area reduction, while exercise training
      provided more protection against fibrosis. Thyroid hormones treatment increased
      the lipoperoxidation and decreased GSHPx activity as compared to MI group,
      increased the t-Akt2 expression as compared to SHAM group, and increased the
      vascular parasympathetic drive. SIGNIFICANCE: Thyroid hormones treatment provided
      differential benefits on the LV function and autonomic modulation as compared to
      the exercise training. Nevertheless, the redox unbalance induced by thyroid
      hormones highlights the importance of more studies targeting the ideal duration
      of this treatment.

PMID- 29366749
TI  - Cathepsin B inhibition attenuates cardiovascular pathology in
      mucopolysaccharidosis I mice.
AB  - Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder with
      multisystemic features, including heart enlargement, heart valve dysfunction, and
      aortic stiffness and dilatation. Previous studies have shown that MPS I mice
      overexpress cathepsin B (CtsB) in multiple tissues, including those from the
      cardiovascular system. Here, we hypothesized that inhibition of CtsB could
      ameliorate cardiac function parameters, as well as aorta and valve abnormalities
      found in MPS I. First, we found that total elastase activity in an MPS I aorta is
      elevated. Following that, we demonstrated that CtsB leaks from the lysosome in
      MPS I human fibroblasts, possibly acting as a degradative agent of extracellular
      matrix components from the aorta, cardiac muscle, and heart valves. We then used
      a CtsB inhibitor in vivo in the MPS I mouse model. After 4 months of treatment,
      partial inhibition of CtsB activity in treated mice reduced aortic dilatation, as
      well as heart valve thickening, and led to improvements in cardiac function
      parameters, although none of these were completely normalized. Based on these
      results, we conclude that lysosomal alterations in this disease promote leakage
      of CtsB to outside the organelle, where this protein can have multiple
      pathological roles. CtsB inhibition improved cardiovascular parameters in MPS I
      mice and can have a potential benefit in this disease.

PMID- 29366750
TI  - Defining the molecular signatures of human right heart failure.
AB  - AIMS: Right ventricular failure (RVF) varies significantly from the more common
      left ventricular failure (LVF). This study was undertaken to determine potential
      molecular pathways that are important in human right ventricular (RV) function
      and may mediate RVF. MATERIALS AND METHODS: We analyzed mRNA of human non-failing
      LV and RV samples and RVF samples from patients with pulmonary arterial
      hypertension (PAH), and post-LVAD implantation. We then performed transcript
      analysis to determine differential expression of genes in the human heart
      samples. Immunoblot quantification was performed followed by analysis of non
      failing and failing phenotypes. KEY FINDINGS: Inflammatory pathways were more
      commonly dysregulated in RV tissue (both non-failing and failing phenotypes). In
      non-failing human RV tissue we found important differences in expression of FIGF,
      TRAPPAC, and CTGF suggesting that regulation of normal RV and LV function are not
      the same. In failing RV tissue, FBN2, CTGF, SMOC2, and TRAPP6AC were
      differentially expressed, and are potential targets for further study.
      SIGNIFICANCE: This work provides some of the first analyses of the molecular
      heterogeneity between human RV and LV tissue, as well as key differences in human
      disease (RVF secondary to pulmonary hypertension and LVAD mediated RVF). Our
      transcriptional data indicated that inflammatory pathways may be more important
      in RV tissue, and changes in FIGF and CTGF supported this hypothesis. In PAH RV
      failure samples, upregulation of FBN2 and CTGF further reinforced the potential
      significance that altered remodeling and inflammation play in normal RV function
      and failure.

PMID- 29366751
TI  - The temporal dynamics of waiting when reward is increasing.
AB  - The temporal dynamics of waiting are complex. The present study used a video game
      involving contingencies that produced differential reinforcement of wait times by
      arranging for the magnitude of the reward to be related to the duration of each
      inter-response time. In previous research, when outcomes were gradually
      increasing in value from a minimum to a maximum, two modes of behavior are
      observed: waiting as little as possible before cashing in (i.e., responding
      rapidly) or waiting until the maximum is available (i.e., responding slowly).
      When outcomes were either a smaller sooner or larger later reward, two modes of
      behavior were again observed which corresponded to choosing either reward
      immediately after it was available. In the present study, outcome values
      increased linearly for a period of time, leveled off, increased abruptly, and
      then increased linearly. This configuration produced three modes of wait times in
      people - responding immediately, responding immediately after the abrupt
      increase, and responding when the maximum possible reward was achieved on each
      trial. Three factors were evaluated as possible causes of each behavioral mode, a
      desire for immediacy or action, the trade-off between molecular and molar
      maximization, and ease of responding.

PMID- 29366752
TI  - Comparison of potentially real versus hypothetical food outcomes in delay and
      probability discounting tasks.
AB  - Much of the research on human delay and probability discounting involves the use
      of hypothetical outcomes, in which participants indicate preferences for outcomes
      but do not receive them. Research generally shows that hypothetical and
      potentially real outcomes are discounted at similar rates. One study, however,
      shows that potentially real cigarettes are discounted more steeply than
      hypothetical cigarettes in smokers, calling into question the generality of the
      finding that potentially real and hypothetical money are discounted at similar
      rates. Using a within-subject design, we tested the extent to which potentially
      real and hypothetical monetary (Experiment 1) and food-related (Experiment 2)
      outcomes were discounted at similar rates. We found mixed results for monetary
      outcomes, in that potentially real outcomes were discounted more steeply than
      hypothetical outcomes when all participants were included; however, this effect
      disappeared when only systematic responders were used. In addition, potentially
      real and hypothetical monetary outcomes were significantly correlated. For food
      related outcomes, we found robust and consistent effects that potentially real
      and hypothetical food outcomes are discounted similarly and that they correlate
      strongly. Generally, these findings suggest that using hypothetical outcomes
      generate similar levels of discounting, in particular for food, which is useful
      for researchers interested in characterizing food-related impulsivity.

PMID- 29366753
TI  - ADHD and comorbid migraine.

PMID- 29366754
TI  - Comments on associations between religiosity and anxiety, depressive symptoms,
      and well-being in Korean adults living with epilepsy.

PMID- 29366755
TI  - Anti-apoptotic activity of human matrix metalloproteinase-2 attenuates diabetes
      mellitus.
AB  - BACKGROUND: Chronic progression of diabetes is associated with decreased
      pancreatic islet mass due to apoptosis of beta-cells. Patients with diabetes have
      increased circulating matrix metalloproteinase-2 (MMP2); however, the
      physiological significance has remained elusive. This study tested the hypothesis
      that MMP2 inhibits cell apoptosis, including islet beta-cells. METHODS: Samples
      from diabetic patients and newly developed transgenic mice overexpressing human
      MMP2 (hMMP2) were harnessed, and diabetes was induced with streptozotocin.
      RESULTS: Circulating hMMP2 was significantly increased in diabetic patients
      compared to controls and significantly correlated with the serum C-peptide
      levels. The diabetic hMMP2 transgenic mice showed significant improvements in
      glycemia, glucose tolerance and insulin secretion compared to diabetic wild type
      mice. Importantly, the increased hMMP2 levels in mice correlated with significant
      reduction in islet beta-cell apoptosis compared to wild-type counterparts, and an
      inhibitor of hMMP2 reversed this mitigating activity against diabetes. The
      increased activation of Akt and BAD induced by hMMP2 in beta-cells compared to
      controls, links this signaling pathway to the anti-apoptotic activity of hMMP2, a
      property that was reversible by both an hMMP2 inhibitor and antibody against
      integrin-beta3. CONCLUSION: Overall, this study demonstrates that increased
      expression of hMMP2 may attenuate the severity of diabetes by protecting islet
      beta-cells from apoptosis through an integrin-mediated activation of the Akt/BAD
      pathway.

PMID- 29366756
TI  - Porcine IFI30 inhibits PRRSV proliferation and host cell apoptosis in vitro.
AB  - Interferon-gamma-inducible protein 30 (IFI30) is an IFN-gamma-inducible protein
      that is involved in MHC class II-restricted antigen processing and MHC class I
      restricted cross-presentation pathways of adaptive immunity. The present study
      aimed to investigate the effects of porcine IFI30 expression on PRRSV
      proliferation in host cells. MARC-145 cells and pig Sertoli (ST) cells were
      infected with PRRSV after transfection with porcine IFI30 expression vectors and
      an empty vector. PRRSV copy numbers were analyzed by absolute real-time
      quantitative PCR, and the results showed that porcine IFI30 expression could
      significantly inhibit PRRSV transcription. Western blot analysis also determined
      that IFI30 expression could reduce the production of PRRSV M protein. Flow
      cytometric analysis indicated that the apoptosis of MARC-145 cells, which are non
      porcine but highly permissive to PRRSV cells, was significantly decreased in the
      IFI30 expression group. In porcine ST cells, apoptosis was significantly
      increased in IFI30 knockdown cells but not in IFI30-overexpressing cells (**p <
      0.01). In conclusion, porcine IFI30 expression may inhibit PRRSV proliferation
      and host cell apoptosis in vitro.

PMID- 29366757
TI  - Expression of homing endonuclease gene and insertion-like element in sea anemone
      mitochondrial genomes: Lesson learned from Anemonia viridis.
AB  - The mitochondrial genomes of sea anemones are dynamic in structure. Invasion by
      genetic elements, such as self-catalytic group I introns or insertion-like
      sequences, contribute to sea anemone mitochondrial genome expansion and
      complexity. By using next generation sequencing we investigated the complete
      mtDNAs and corresponding transcriptomes of the temperate sea anemone Anemonia
      viridis and its closer tropical relative Anemonia majano. Two versions of fused
      homing endonuclease gene (HEG) organization were observed among the Actiniidae
      sea anemones; in-frame gene fusion and pseudo-gene fusion. We provided support
      for the pseudo-gene fusion organization in Anemonia species, resulting in a
      repressed HEG from the COI-884 group I intron. orfA, a putative protein-coding
      gene with insertion-like features, was present in both Anemonia species.
      Interestingly, orfA and COI expression were significantly up-regulated upon long
      term environmental stress corresponding to low seawater pH conditions. This study
      provides new insights to the dynamics of sea anemone mitochondrial genome
      structure and function.

PMID- 29366758
TI  - Transcriptomic profiling reveals gene expression kinetics in patients with
      hypoxia and high altitude pulmonary edema.
AB  - OBJECTIVE: High altitude pulmonary edema (HAPE) is a life threatening condition
      occurring in otherwise healthy individuals who rapidly ascend to high altitude.
      However, the molecular mechanisms of its pathophysiology are not well understood.
      The objective of this study is to evaluate differential gene expression in
      patients with HAPE during acute illness and subsequent recovery. METHODS: Twenty
      one individuals who ascended to an altitude of 3780 m were studied, including 12
      patients who developed HAPE and 9 matched controls without HAPE. Whole-blood
      samples were collected during acute illness and subsequent recovery for analysis
      of the expression of hypoxia-related genes, and physiologic and laboratory
      parameters, including mean pulmonary arterial pressure (mPAP), heart rate, blood
      pressure, and arterial oxygen saturation (SpO2), were also measured. RESULTS:
      Compared with control subjects, numerous hypoxia-related genes were up-regulated
      in patients with acute HAPE. Gene network analyses suggested that HIF-1alpha
      played a central role in acute HAPE by affecting a variety of hypoxia-related
      genes, including BNIP3L, VEGFA, ANGPTL4 and EGLN1. Transcriptomic profiling
      revealed the expression of most HAPE-induced genes was restored to a normal level
      during the recovery phase except some key hypoxia response factors, such
      asBNIP3L, EGR1, MMP9 and VEGF, which remained persistently elevated. CONCLUSIONS:
      Differential expression analysis of hypoxia-related genes revealed distinct
      molecular signatures of HAPE during acute and recovery phases. This study may
      help us to better understand HAPE pathogenesis and putative targets for further
      investigation and therapeutic intervention.

PMID- 29366759
TI  - A senescence-delaying pre-culture medium for transcriptomics of Podospora
      anserina.
AB  - Podospora anserina is an efficient degrader of recalcitrant plant biomass but
      senesces quickly on most standard pre-culturing media. Among nine pre-culture
      media, sufficient growth without senescence was only observed on Luria-Bertani
      medium. The high quality RNA obtained from subsequent transfer cultures was
      suitable for transcriptomics.

PMID- 29366760
TI  - Rapid and cost-effective identification and antimicrobial susceptibility testing
      in patients with Gram-negative bacteremia directly from blood-culture fluid.
AB  - Rapid pathogen identification (ID) and antimicrobial susceptibility testing (AST)
      in bacteremia cases or sepsis could improve patient prognosis. Thus, it is
      important to provide timely reports, which make it possible for clinicians to set
      up appropriate antibiotic therapy during the early stages of bloodstream
      infection (BSI). This study evaluates an in-house microbiological protocol for
      early ID as well as AST on Gram negative bacteria directly from positive
      monomicrobial and polymicrobial blood cultures (BCs). A total of 102 non
      duplicated positive BCs from patients with Gram-negative bacteremia were tested.
      Both IDs and ASTs were performed from bacterial pellets extracted directly from
      BCs using our protocol, which was applied through the combined use of a MALDI-TOF
      MS and Vitek2 automated system. The results of our study showed a 100% agreement
      in bacterial ID and 98.25% categorical agreement in AST when compared to those
      obtained by routine conventional methods. We recorded only a 0.76% minor error
      (mE), 0.76% major error (ME) and a 0.20% very major error (VME). Moreover, the
      turnaround time (TAT) regarding the final AST report was significantly shortened
      (DeltaTAT = 8-20 h, p < 0.00001). This in-house protocol is rapid, easy to
      perform and cost effective and could be successfully introduced into any clinical
      microbiology laboratory. A final same-day report of ID and AST improves patient
      management, by early and appropriate antimicrobial treatment and could
      potentially optimize antimicrobial stewardship programs.

PMID- 29366761
TI  - Carbon dots: emerging theranostic nanoarchitectures.
AB  - Nanotechnology has gained significant interest from biomedical and analytical
      researchers in recent years. Carbon dots (C-dots), a new member of the carbon
      nanomaterial family, are spherical, nontoxic, biocompatible, and discrete
      particles less than 10nm in diameter. Research interest has focused on C-dots
      because of their ultra-compact nanosize, favorable biocompatibility, outstanding
      photoluminescence, superior electron transfer ability, and versatile surface
      engineering properties. C-dots show significant potential for use in cellular
      imaging, biosensing, targeted drug delivery, and other biomedical applications.
      Here we discuss C-dots, in terms of their physicochemical properties, fabrication
      techniques, toxicity issues, surface engineering and biomedical potential in drug
      delivery, targeting as well as bioimaging.

PMID- 29366762
TI  - The rise of deep learning in drug discovery.
AB  - Over the past decade, deep learning has achieved remarkable success in various
      artificial intelligence research areas. Evolved from the previous research on
      artificial neural networks, this technology has shown superior performance to
      other machine learning algorithms in areas such as image and voice recognition,
      natural language processing, among others. The first wave of applications of deep
      learning in pharmaceutical research has emerged in recent years, and its utility
      has gone beyond bioactivity predictions and has shown promise in addressing
      diverse problems in drug discovery. Examples will be discussed covering
      bioactivity prediction, de novo molecular design, synthesis prediction and
      biological image analysis.

PMID- 29366763
TI  - Long-term preservation of freeze-dried rabbit sperm by adding rosmarinic acid and
      different chelating agents.
AB  - Freeze-drying (FD) technique has been applied as an alternative technology to
      preserve gene resources to allow simple sperm preservation and shipment at 4 
      degrees C. Nevertheless, DNA sperm might be damaged by mechanical or oxidative
      stress throughout FD procedure. Therefore, suitable protection to maintain DNA
      integrity is required. The aim of this study was to determine the effect of
      rosmarinic acid (RA) as an antioxidant and two chelating agents (EGTA and EDTA)
      on the DNA integrity of freeze-dried rabbit sperm after storage of the samples at
      4  degrees C and room temperature for 8 months. Rabbit sperm were freeze-dried in
      basic medium (10 mM Tris-HCl buffer and 50 mM NaCl) supplemented with 50 mM EGTA
      (1), 50 mM EGTA plus 105 MUM RA (2), 50 mM EDTA (3) or 50 mM EDTA plus 105 MUM RA
      (4). Semen samples were kept at 4  degrees C and room temperature during 8
      months. After rehydration, DNA integrity was evaluated with Sperm Chromatin
      Dispersion test observing that DNA fragmentation was higher when semen samples
      were freeze-dried with EGTA (10.9%) than with EDTA (4.1%) (p < 0.01).
      Furthermore, RA acted better under adverse conditions and no significant
      differences were found in temperature storage. Summarizing, FD is a method that
      can allow simple gene resources preservation among 4  degrees C to 25  degrees C
      during 8 months and transportation without the need for liquid nitrogen or dry
      ice. EDTA chelating agent is the most suitable media for freeze-dried rabbit
      sperm and the addition of RA protects the DNA against the oxidative stress caused
      during FD procedure.

PMID- 29366764
TI  - Deglycerolization of red blood cells: A new dilution-filtration system.
AB  - In this work, we present a new version of the dilution-filtration system for
      rapidly deglycerolizing a large volume of cryopreserved blood. In our earlier
      system, one of the major problems was the damage induced to the red blood cells
      (RBCs) due to high osmolality change at the dilution point. Therefore, we devised
      a new system to solve this problem. First, we theoretically simulated the
      osmolality variation in the new system and the variation of the maximum and
      minimum volumes of the RBCs at the dilution point to examine the effects of
      operating parameters/conditions. Next, we experimentally validated the effects of
      these operating parameters by deglycerolizing porcine blood. The results show
      that when the initial NaCl concentration in the hypertonic solution is 18%, the
      volume of the hypertonic solution is 200 mL, and the flow rate of the filtrate is
      50 mL/min, the system can effectively remove glycerin from 200 mL of porcine
      blood in 30 min, with ~87% RBC survival rate and ~73% RBC recovery rate. Our
      results indicated that in the new system the concentration and the volume of the
      hypertonic solution used to dilute the blood are the important parameters that
      need to be adjusted to reduce osmotic damage to the RBCs. In addition, a fast
      filtrate flow rate is highly recommended. This work can significantly contribute
      to the development of a more efficient and effective system for deglycerolizing
      large volumes of cryopreserved blood in clinic.

PMID- 29366765
TI  - Active principles of Tetradenia riparia. IV. Anthelmintic activity of 8(14),15
      sandaracopimaradiene-7alpha,18-diol.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tetradenia (T.) riparia (Hochst.) Codd
      (Lamiaceae), formerly known as Iboza riparia (Hochst.) N.E.Br., is one of the
      most frequently used medicinal plants in traditional Rwandese medicine. It was
      used as a remedy against a wide range of diseases including malaria, angina,
      yaws, dental abscesses, headache, worm infections and several kinds of fevers and
      aches. AIM OF THE STUDY: This study aims to identify the compounds active against
      helminths from Tetradenia riparia. METHODS: A bioassay-guided isolation of
      anthelmintic compounds from the leaves of Tetradenia riparia was performed using
      a Caenorhabditis elegans (C. elegans) testing model. RESULTS: The bioassay-guided
      isolation led to one active compound, i.e. 8(14),15-sandaracopimaradiene
      7alpha,18-diol. Its IC50 value was 5.4 +/- 0.9 ug/mL (17.8 +/- 2.9 uM).
      CONCLUSIONS: We identified the bioactive compound from Tetradenia riparia
      responsible for its anthelmintic activity: 8(14),15-sandaracopimaradiene
      7alpha,18-diol. Although the compound and several of its bioactivities have been
      described before, this is the first report of its anthelmintic effect.

PMID- 29366766
TI  - Breast cancer amelioration by Butea monosperma in-vitro and in-vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Butea monosperma belonging to family Fabaceae is
      used in the Indian traditional medicine (Ayurveda) for various ailments including
      abdominal tumors and possess anti-estrogenic activity. AIM OF THE STUDY: The
      present study is aimed at investigating the chemo-preventive potential of Butea
      monosperma in breast cancer and elucidating it's mechanism of action by assessing
      its effect on key processes like apoptosis, angiogenesis and metastasis. METHODS:
      Cytotoxic potential of methanol extract of Butea monosperma flower (MEBM) was
      tested in MCF-7 (estrogen receptor positive), MDA-MB-231 (triple negative) and
      MDA-MB-453 (HER2 positive) human breast cancer cells by MTT assay. Chemo
      preventive potential was evaluated in-vivo in Methylnitrosourea (MNU) induced
      mammary cancer in nulliparous Sprague-Dawley rats. The mechanism for anticancer
      potential was screened by in-vitro studies involving Annexin V- FITC assay
      (apoptosis), Chick Chorioallantoic Membrane assay (angiogenesis) and Migration
      assay (metastasis). Statistical analysis was done by one way and two way ANOVA
      (for Growth Rate and feed consumption efficiency) followed by post hoc
      Bonferroni's test with P value < 0.05. RESULTS: It is observed that the exposure
      of MEBM, at various concentrations and time intervals to different cell lines,
      resulted in decreased cell proliferation. The IC50 value of MCF-7 cells was found
      significantly less than that of MDA-MB-231 and MDA-MB-453 cells, which indicated
      that the extract of said medicinal plant were more potent inhibitors of estrogen
      positive breast cancer cells than other types of breast cancer cells in vitro.
      Corroborative evidences were acquired in MNU actuated mammary carcinogenesis
      where MEBM constricted tumor parameters, decreased expression of estrogen and
      progesterone, nucleic acid content and increased latency period. MEBM also
      induced apoptosis, inhibited angiogenesis and metastasis in-vitro. CONCLUSION:
      Selective cytotoxic activity in MCF-7 estrogen positive breast cancer cells and
      inhibition of growth of mammary carcinoma in-vivo by methanol extract of Butea
      monosperma flowers (MEBM) suggests chemo-prevention through modulation of
      estrogen and progesterone receptor, apoptotic, anti-angiogenesis and anti
      metastatic activity.

PMID- 29366767
TI  - Concurrent use of Chinese herbal medicine among hormone users and its association
      with ischemic stroke risk: A population-based study.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies had indicated that hormone
      therapy (HT) may increase the risk of ischemic stroke (IS) in menopausal women.
      However, little is known about the benefits and risks of use of Chinese herbal
      medicine (CHM) in conditions related to hormone use. The aim of this study is to
      explore the risk of IS in menopausal women treated with HT and CHM. MATERIALS AND
      METHODS: A total of 32,441 menopausal women without surgical menopause aged 40-65
      years were selected from 2003 to 2010 using the 2-million random samples of the
      National Health Insurance Research Database in Taiwan. According to the
      medication usage of HT and CHM, we divided the current and recent users into two
      groups: an HT use-only group (n = 4989) and an HT/CHM group (n = 9265).
      Propensity-score matching samples (4079 pairs) were further created to deal with
      confounding by indication. The adjusted hazard ratios (HR) of IS were estimated
      by the robust Cox proportional hazards model. RESULTS: The incidence rate of IS
      in the HT/CHM group was significantly lower than in the HT group (4.5 vs. 12.8
      per 1000 person-year, p < 0.001). Multivariate analysis results indicated that
      additional CHM use had a lower risk of IS compared to the HT group (HR = 0.3; 95%
      confidence interval [CI], 0.21-0.43). Further subgroup analyses and sensitivity
      analyses had similar findings. CONCLUSION: We found that combined use of HT and
      CHM was associated with a lower risk of IS. Further study is needed to examine
      possible mechanism underlying this association.

PMID- 29366768
TI  - Ginseng polysaccharides enhanced ginsenoside Rb1 and microbial metabolites
      exposure through enhancing intestinal absorption and affecting gut microbial
      metabolism.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Polysaccharides and small molecules commonly co
      exist in decoctions of traditional Chinese medicines (TCMs). Our previous study
      outlined that ginseng polysaccharides (GP) could interact with co-existing
      ginsenosides to produce synergistic effect in an over-fatigue and acute cold
      stress model via gut microbiota involved mechanisms. AIM OF THE STUDY: This study
      aimed to verify the interactions by examining the impact of GP on oral
      pharmacokinetics of ginsenoside Rb1 (Rb1), the dominant protopanoxadiol (PPD)
      type ginsenoside in Ginseng, on a dextran sulphate sodium (DSS) induced
      experimental colitis model which was characterized by gut dysbiosis, and to
      delineate the underlying mechanisms in vitro. MATERIALS AND METHODS: Rats
      received drinking water (normal group), 5% DSS (UC group), or 5% DSS plus daily
      oral administration of GP (GP group) for 7 days and fecal samples were collected
      on day -3, 0 and 6. On day 7 all animals received an oral dosage of Rb1 and blood
      samples were withdrawn for pharmacokinetic study. The in vitro metabolism study
      of Rb1 in gut microbiota from normal and UC rats and the transport study of Rb1
      across Caco-2 cell monolayer were carried out in presence/absence of GP. Rb1 and
      its bacterial metabolites ginsenoside Rd (Rd), ginsenoside F2 (F2), Compound K
      (CK) and PPD were determined using LC-MS/MS. Total and target bacteria in fecal
      samples were determined by using 16S rRNA-based RT-PCR. beta-Glucosidase activity
      was determined by measuring 4-nitrophenol formed from 4-nitrophenyl-beta-D
      glucopyranoside hydrolysis. RESULTS: DSS induction did not alter AUC0-t and Cmax
      of Rb1, which, however, were doubled together with elevated AUC0-t of the
      metabolites, in particular Rd and CK, in GP group. GP influenced the microbial
      composition and showed a prebiotic-like effect. Accordingly, GP treatment could
      partially restore the beta-glucosidase activity which was reduced by DSS
      induction. The presence of GP resulted in quicker microbial metabolism of Rb1 and
      higher Rd formation in first 8 h of incubation, while the impact on F2 and CK
      formation/conversion became obvious after 8 h. More interestingly, GP slightly
      stimulated Caco-2 cell growth and facilitated Rb1 transport across the Caco-2
      monolayer in both directions, increasing the Papp of Rb1 from 10-7 cm/s to 10-6
      cm/s. CONCLUSIONS: GP alleviated DSS-induced colitis-like symptoms and enhanced
      the systemic exposure of Rb1 through enhancing microbial deglycosylation and
      intestinal epithelial absorption of Rb1. These findings further demonstrated the
      important role of gut microbiota in the multifaceted action of polysaccharides in
      the holistic actions of traditional decoction of TCMs.

PMID- 29366769
TI  - Network pharmacology-based strategy for predicting active ingredients and
      potential targets of Yangxinshi tablet for treating heart failure.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Yangxinshi tablet (YXST) is an effective
      treatment for heart failure and myocardial infarction; it consists of 13 herbal
      medicines formulated according to traditional Chinese Medicine (TCM) practices.
      It has been used for the treatment of cardiovascular disease for many years in
      China. MATERIALS AND METHODS: In this study, a network pharmacology-based
      strategy was used to elucidate the mechanism of action of YXST for the treatment
      of heart failure. Cardiovascular disease-related protein target and compound
      databases were constructed for YXST. A molecular docking platform was used to
      predict the protein targets of YXST. The affinity between proteins and
      ingredients was determined using surface plasmon resonance (SPR) assays. The
      action modes between targets and representative ingredients were calculated using
      Glide docking, and the related pathways were predicted using the Kyoto
      Encyclopedia of Genes and Genomes (KEGG) database. RESULTS: A protein target
      database containing 924 proteins was constructed; 179 compounds in YXST were
      identified, and 48 compounds with high relevance to the proteins were defined as
      representative ingredients. Thirty-four protein targets of the 48 representative
      ingredients were analyzed and classified into two categories: immune and
      cardiovascular systems. The SPR assay and molecular docking partly validated the
      interplay between protein targets and representative ingredients. Moreover, 28
      pathways related to heart failure were identified, which provided directions for
      further research on YXST. CONCLUSIONS: This study demonstrated that the
      cardiovascular protective effect of YXST mainly involved the immune and
      cardiovascular systems. Through the research strategy based on network
      pharmacology, we analysis the complex system of YXST and found 48 representative
      compounds, 34 proteins and 28 related pathways of YXST, which could help us
      understand the underlying mechanism of YSXT's anti-heart failure effect. The
      network-based investigation could help researchers simplify the complex system of
      YXSY. It may also offer a feasible approach to decipher the chemical and
      pharmacological bases of other TCM formulas.

PMID- 29366770
TI  - Intrathecal administration of autologous bone marrow stromal cells improves
      neuropathic pain in patients with spinal cord injury.
AB  - Neuropathic pain (NP) is highly disabling, responds poorly to pharmacological
      treatment, and represents a significant cause of decreased quality of life in
      patients suffering from spinal cord injury (SCI). In recent years, cell therapy
      with autologous mesenchymal stromal cells (MSCs) has been considered as a
      potential therapeutic weapon in this entity. Ten patients suffering chronic SCI
      received 100 million MSCs into subarachnoid space by lumbar puncture (month 1 of
      the study) and this procedure was repeated at months 4 and 7 until reaching a
      total doses of 300 million MSCs. Intensity of NP was measured by standard
      numerical rating scale (VAS) from 0 to 10, recording scores previous to the first
      MSCs administration and monthly, until month 10 of follow-up. Months 1, 4, 7 and
      10 of the study were selected as time points in order to a statistical analysis
      by the nonparametric Wilcoxon rank test. Our results showed significant and
      progressive improvement in NP intensity after the first administration of MSCs
      (p: 0.003). This study supports the benefit of intrathecal administration of
      autologous MSCs for the treatment of NP in patients with SCI.

PMID- 29366771
TI  - Conflict monitoring in multi-sensory flanker tasks: Effects of cross-modal
      distractors on the N2 component.
AB  - The N2 component is a well-known neural correlate of conflict monitoring (CM),
      being more negative in the presence of conflicting information in visual conflict
      tasks. However, whether to-be-ignored auditory distractors can introduce
      additional conflict remains unknown. In the present work, subjects performed a
      visual (V) and audiovisual (AV) version of a Go/NoGo flanker task, and responded
      only if the target arrow pointed toward a pre-specified direction (e.g., left).
      In the AV task, in which to-be-ignored auditory distractors that were
      semantically associated with the flankers were concurrently presented, the
      congruency effect on both RT and N2 amplitude was enhanced, confirming that
      additional conflict can be brought about by cross-modal distractors at both
      behavioural and neural levels. Consistent with the hypothesis that N2 amplitude
      reflects response conflict in visual conflict tasks, within-subject correlation
      between N2 amplitude and RT was significant in the Go conditions for the V task
      (congruent/incongruent). However, for the AV task, the correlation was
      significant only in the congruent condition. These findings suggest that while
      the cross-modal conflict is registered by the CM process, only part of this
      conflict could effectively induce response conflict.

PMID- 29366773
TI  - The new guidelines for hypertension: Navigating between Scylla and Charybdis of
      clinical practice.

PMID- 29366772
TI  - Validation of a targeted next generation sequencing-based comprehensive
      chromosome screening platform for detection of triploidy in human blastocysts.
AB  - Triploidy accounts for ~2% of natural pregnancies and 15% of cytogenetically
      abnormal miscarriages. This study aimed to validate triploidy detection in human
      blastocysts, its frequency and parental origin using genotyping data generated in
      parallel with chromosome copy number analysis by a targeted next generation
      sequencing (tNGS)-based comprehensive chromosome screening platform. Phase 1:
      diploid and triploid control samples were blinded, sequenced by tNGS and
      karyotype predictions compared for accuracy. Phase 2: tNGS was used to calculate
      the frequency of triploidy in 18,791 human blastocysts from trophectoderm (TE)
      biopsies. Phase 3: parental origin of the inherited extra alleles was evaluated
      by sequencing parental gDNA to validate triploidy predictions from Phase 2. All
      karyotypes and ploidy in controls from Phase 1 were correctly predicted by two
      independent methods. A blastocyst triploidy frequency of 0.474% (89/18,791) was
      observed in Phase 2 of the study. Finally, five suspected triploid blastocysts
      with parental DNA available were confirmed to be triploid and of maternal origin.
      tNGS provides higher sequencing depth in contrast to other contemporary NGS
      platforms, allowing for accurate single nucleotide polymorphism calling and
      accurate detection of triploidy in TE biopsies. Triploidy in intracytoplasmic
      sperm injection-derived blastocysts is rare and mostly of maternal origin.

PMID- 29366774
TI  - Transapical closure of multiple mitral paravalvular leaks with dual device
      deployment through a single sheath: a Heart Team job.

PMID- 29366775
TI  - Metformin regulates mitochondrial biogenesis and senescence through AMPK mediated
      H3K79 methylation: Relevance in age-associated vascular dysfunction.
AB  - Endothelial senescence in conjunction with mitochondrial dysfunction orchestrates
      age-associated cardiovascular disorders. In this study we investigated the causal
      link between these two processes and studied the molecular mechanisms by which
      metformin acts to coordinate the delay of endothelial senescence via enhancing
      mitochondrial biogenesis/function. AMPK activators metformin and AICAR delayed
      endothelial senescence via SIRT1-mediated upregulation of DOT1L, leading to
      increased trimethylation of H3K79 (H3K79me3). Treatment of cells with either
      siAMPK or siSIRT1 repressed DOT1L-mediated enhancement of H3K79me3. Moreover, the
      increase in SIRT3 expression and mitochondrial biogenesis/function by AMPK
      activators was H3K79me-dependent as H3K79N mutant or siDOT1L abrogated these
      effects. This was confirmed by the enrichment of H3K79me3 in the SIRT3 promoter
      with AMPK activation. Intriguingly, enhanced PGC-1alpha expression by SIRT3 via
      AMPK activation was responsible for increased hTERT expression and delayed
      endothelial senescence. In contrast, SIRT3 knockdown caused increased oxidative
      stress and premature senescence, possibly by depleting hTERT expression.
      Furthermore, a chronic low dose administration of metformin significantly
      attenuated vascular aging and inhibited age-associated atherosclerotic plaque
      formation in ApoE-/- mice. Overall, the results of this study show a novel
      regulation of mitochondrial biogenesis/function, and cellular senescence by
      H3K79me acting through SIRT3, thus providing a molecular basis for metformin
      mediated age-delaying effects.

PMID- 29366776
TI  - Inhibition of lysyl oxidase-like 1 (LOXL1) expression arrests liver fibrosis
      progression in cirrhosis by reducing elastin crosslinking.
AB  - Mature crosslinked-poly-elastin deposition has been found to be associated with
      liver fibrosis. However, the regulation of crosslinked/insoluble elastin in liver
      fibrosis remains largely unknown. Here, we investigated the contribution of lysyl
      oxidases (LOXs) family, mediated elastin crosslinking, to liver fibrogenesis. We
      established carbon tetrachloride (CCl4)-induced liver fibrotic and cirrhotic
      models and found that crosslinked/insoluble elastin levels spiked only in
      cirrhosis stage during disease progression, in comparison to collagen Iota levels
      which increased continuously though all stages. Among the LOXs family members,
      only LOX-like 1 (LOXL1) levels were coincident with the appearance of
      crosslinked/insoluble elastin. These coincidences included that LOXL1 expression
      increased (34 fold) in cirrhosis, localized with alpha-smooth muscle actin (SMA)
      and was absent in normal and fibrotic livers. In LX-2 cells, LOXL1 silencing
      arrested expression of alpha-SMA, elastin and collagen Iota. Our previously
      characterized adeno-associated vector (AAV) 2/8 shRNA was shown to effectively
      downregulate LOXL1 expression in CCl4 induced fibrosis mice models. These
      resulted in delicate and thinner septa and less crosslinked elastin, with a 58%
      loss of elastin area and 51% decrease of collagen area. Our findings strongly
      suggested that elastin crosslinking and LOXL1 were co-associated with liver
      cirrhosis, while selective inhibition of LOXL1 arrested disease progression by
      reducing crosslinking of elastin.

PMID- 29366778
TI  - The liver X receptors and sterol regulatory element binding proteins alter
      progesterone secretion and are regulated by human chorionic gonadotropin in human
      luteinized granulosa cells.
AB  - There is increased expression of liver x receptor (LXR) target genes and reduced
      low density lipoprotein receptor (LDLR) during spontaneous luteolysis in
      primates. The LXRs are nuclear receptors that increase cholesterol efflux by
      inducing transcription of their target genes. Transcription of LDLR is regulated
      by sterol regulatory element binding proteins (SREBPs). Human chorionic
      gonadotropin (hCG) prevents luteolysis and stimulates progesterone synthesis via
      protein kinase A (PKA). Thus, our primary objectives are: 1) Determine the
      effects of LXR activation and SREBP inhibition on progesterone secretion and
      cholesterol metabolism, and 2) Determine whether hCG signaling via PKA regulates
      transcription of LXR and SREBP target genes in human luteinized granulosa cells.
      Basal and hCG-stimulated progesterone secretion was significantly decreased by
      the combined actions of the LXR agonist T0901317 and the SREBP inhibitor
      fatostatin, which was associated with reduced intracellular cholesterol storage.
      Expression of LXR target genes in the presence of T0901317 was significantly
      reduced by hCG, while hCG promoted transcriptional changes that favor LDL uptake.
      These effects of hCG were reversed by a specific PKA inhibitor. A third objective
      was to resolve a dilemma concerning LXR regulation of steroidogenic acute
      regulatory protein (STAR) expression in primate and non-primate steroidogenic
      cells. T0901317 induced STAR expression and progesterone synthesis in ovine, but
      not human cells, revealing a key difference between species in LXR regulation of
      luteal function. Collectively, these data support the hypothesis that LXR-induced
      cholesterol efflux and reduced LDL uptake via SREBP inhibition mediates
      luteolysis in primates, which is prevented by hCG.

PMID- 29366777
TI  - The Common and Distinct Features of Brown and Beige Adipocytes.
AB  - Two types of thermogenic fat cells, brown adipocytes and beige adipocytes, play a
      key role in the regulation of systemic energy homeostasis in mammals. Both brown
      fat and beige fat possess thermogenic properties in addition to common
      morphological and biochemical characteristics, including multilocular lipid
      droplets and cristae-dense mitochondria. Recent studies also identify features
      that are distinct between the two types of thermogenic fat cells, such as their
      developmental regulation and function. Of particular interest is the role of
      beige fat in the regulation of glucose homeostasis via uncoupling protein 1
      (UCP1)-independent mechanisms. A better understanding of the underlying causes of
      these characteristics of brown and beige fat will allow us to specifically
      manipulate these cells to improve systemic energy metabolism and glucose
      homeostasis.

PMID- 29366779
TI  - Splicing activator RNPS1 suppresses errors in pre-mRNA splicing: A key factor for
      mRNA quality control.
AB  - Human RNPS1 protein was first identified as a pre-mRNA splicing activator in
      vitro and RNPS1 regulates alternative splicing in cellulo. RNPS1 was also known
      as a peripheral factor of the exon junction complex (EJC). Here we show that
      cellular knockdown of RNPS1 induced a reduction of the wild-type aurora kinase B
      (AURKB) protein due to the induced aberrant pre-mRNA splicing events, indicating
      that the fidelity of AURKB pre-mRNA splicing was reduced. The major aberrant
      AURKB mRNA was derived from the upstream pseudo 5' and 3' splice sites in intron
      5, which resulted in the production of the non-functional truncated AURKB
      protein. AURKB, is an essential mitotic factor, whose absence is known to cause
      multiple nuclei, and this multinucleation phenotype was recapitulated in RNPS1
      knockdown cells. Importantly this RNPS1-knockdown phenotype was rescued by
      ectopic expression of AURKB, implying it is a major functional target of RNPS1.
      We found RNPS1 protein, not as a component of the EJC, binds directly to a
      specific element in the AURKB exon upstream of the authentic 5' splice site, and
      this binding is required for normal splicing. RNPS1-knockdown induces a parallel
      aberrant splicing pattern in a fully distinct pre-mRNA, MDM2, suggesting that
      RNPS1 is a global guardian of splicing fidelity. We conclude that RNPS1 is a key
      factor for the quality control of mRNAs that is essential for the phenotypes
      including cell division.

PMID- 29366780
TI  - MicroRNA-29a mitigation of toll-like receptor 2 and 4 signaling and alleviation
      of obstructive jaundice-induced fibrosis in mice.
AB  - Cholestasis and hepatitis can cause continuous liver damage that may ultimately
      result in liver fibrosis. In a previous study, we demonstrated that microRNA-29a
      (miR-29a) protects against liver fibrosis. Toll-like receptor 2 (TLR2) and TLR4
      are pattern recognition receptors of bacterial lipoprotein and
      lipopolysaccharide, both of which participate in activating hepatic stellate
      cells and liver fibrosis. The purpose of this study is to characterize the
      biological influence of miR-29a on TLR2 and TLR4 signaling in livers injured with
      bile duct ligation (BDL). We performed BDL on both miR-29a transgenic mice (miR
      29aTg) and wild-type mice to induce cholestatic liver injury. Primary HSCs were
      transfected with a miR-29a mimic and inhibitor. In the wild-type mice, the BDL
      demonstrated significant alpha-smooth muscle actin fibrotic matrix formation and
      hepatic high mobility group box-1 expression. However, in the miR-29aTg mice,
      these factors were significantly reduced. Furthermore, miR-29a overexpression
      reduced the BDL exaggeration of TLR2, TLR4, MyD88, bromodomain-containing protein
      4 (BRD4), phospho-p65 as well as proinflammatory cytokines, IL-1beta, MCP-1, TGF
      beta, and TNF-alpha. In vitro, miR-29a mimic transfection reduced alpha-SMA,
      BRD4,TLR2, and TLR4 expressions in HSCs. This study provides new molecular
      insight into the ability of miR-29a to inhibit TLR2 and TLR4 signaling, which
      thus slows the progression of cholestatic liver deterioration.

PMID- 29366781
TI  - HBx-elevated SIRT2 promotes HBV replication and hepatocarcinogenesis.
AB  - Sirtuin 2 (SIRT2) is a class III histone deacetylase that has been implicated to
      promote HCC development. However, the functional role of SIRT2 in HBV is still
      unclear. In this study, we found that HBV could upregulate SIRT2 expression.
      Additionally, HBx could activate SIRT2 promoter to upregulate the mRNA and
      protein level of SIRT2. Furthermore, we found that SIRT2 could facilitate HBV
      transcription and replication. Finally, we demonstrated that upregulation of
      SIRT2 by HBx promoted hepatocarcinogenesis. In summary, our findings revealed a
      novel function of SIRT2 in HBV and HBV-mediated HCC. First, SIRT2 could promote
      HBV replication. And then HBx-elevated SIRT2 could enhance the transformation of
      HBV-mediated HCC. Those findings highlight the potential role of SIRT2 in HBV and
      HBV-mediated HCC by interaction with HBx.

PMID- 29366783
TI  - WITHDRAWN: SIKE1 deficiency accelerates hepatic ischemia/reperfusion (IR) injury
      through enhancing Toll-like receptor-3-regulated inflammation.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29366782
TI  - Up-regulation of MSH6 is associated with temozolomide resistance in human
      glioblastoma.
AB  - The impact of DNA mismatch repair (MMR) on resistance to temozolomide (TMZ)
      therapy in patients with glioblastoma (GBM) is recently reported but the
      mechanisms are not understood. We aim to analyze the correlation between MMR
      function and the acquired TMZ resistance in GBM using both relevant clinical
      samples and TMZ resistant cells. First we found increased expression of MSH6, one
      of key components of MMR, in recurrent GBM patients' samples who underwent TMZ
      chemotherapy, comparing with those matched samples collected at the time of
      diagnosis. Using the cellular models of acquired resistance to TMZ, we further
      confirmed the up-regulation of MSH6 in TMZ resistant cells. Moreover, a TCGA
      dataset contains a large cohort of GBM clinical samples with or without TMZ
      treatment reinforced the increased expression of MSH6 and other MMR genes after
      long-term TMZ chemotherapy, which may resulted in MMR dysfunction and acquired
      TMZ resistance. Our results suggest that increased expression of MSH6, or other
      MMR, may be a new mechanism contributing to the acquired resistance during TMZ
      therapy; and may serve as an indicator to the resistance in GBM.

PMID- 29366784
TI  - Identification of novel Amurin-2 variants from the skin secretion of Rana
      amurensis, and the design of cationicity-enhanced analogues.
AB  - Rana amurensis is important in Chinese medicine as its skin secretions contain
      abundant bioactive peptides. Here, we have identified the antimicrobial peptide
      Amurin-2 and three highly-conserved variants, Amurin-2a, Amurin-2b and Amurin-2c
      through a combination of molecular cloning and MS/MS fragmentation sequencing.
      Synthetic replicates of these peptides demonstrate potent antimicrobial activity
      against S. aureus, whilst some have activity against C.albicans and even
      resistant bacterial MRSA. Furthermore, two Lys-analogues (K4-Amurin-2 and K11
      Amurin-2) were designed to improve the bioactive function and the antimicrobial
      activity of K4-Amurin-2 against E.coli was enhanced distinctly. In addition, the
      two modified peptides also showed more potent activity against S. aureus, C.
      albicans and MRSA strains. Meanwhile, these peptides showed inhibitory effect on
      the cell viability of several cancer cells. As a result, these structural and
      functional studies of Amurin-2 variants and analogues could provide insights for
      future antimicrobial peptide design.

PMID- 29366786
TI  - SMAD7 methylation as a novel marker in atherosclerosis.
AB  - Atherosclerosis is a complicated process comprising inflammation, accumulation of
      collagen matrix and aberrant DNA methylation. SMAD7 is known to play an important
      role in fibrosis and inflammation. In recent years, increasing research has
      concentrated on the connection between DNA methylation and atherosclerosis. The
      current study was designed to investigate methylation status of some specific
      gene with a focus on SMAD7 in atherosclerosis and elucidate their relationship.
      We found that SMAD7 expression was decreased and its promoter region was markedly
      methylated in atherosclerotic plaques when compared with normal artery walls.
      Using MALDI-TOF MS, increased DNA methylation levels of SMAD7 promoter at CpG
      unit 5.8.15.16 were found in peripheral blood of atherosclerosis patients
      relative to matched normal controls, respectively. Correlation analysis revealed
      that mean DNA methylation levels of SMAD7 promoter of CpG unit 5.8.15.16 were
      positively associated with homocysteine levels (r = 0.724, p < .001) and carotid
      plaque scores(r = 0.790, p < .001). SMAD7 promoter is hyper-methylated both in
      human atherosclerotic plaques and atherosclerosis patients, which is positively
      associated with homocysteine levels and carotid plaque scores. Thus, methylated
      SMAD7 may be a novel predicted marker and therapeutics target for
      atherosclerosis.

PMID- 29366785
TI  - 1alpha,25-dihydroxyvitamin D3 mitigates cancer cell mediated mitochondrial
      dysfunction in human skeletal muscle cells.
AB  - Cancer cachexia is associated with muscle weakness and atrophy. We investigated
      whether 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), which has previously
      been shown to increase skeletal myoblast oxygen consumption rate, could reverse
      the deleterious effects of tumor cell conditioned medium on myoblast function.
      Conditioned medium from Lewis lung carcinoma (LLC1) cells inhibits oxygen
      consumption, increases mitochondrial fragmentation, inhibits pyruvate
      dehydrogenase activity, and enhances proteasomal activity in human skeletal
      muscle myoblasts. 1alpha,25(OH)2D3 reverses the tumor cell-mediated changes in
      mitochondrial oxygen consumption and proteasomal activity, without changing
      pyruvate dehydrogenase activity. 1alpha,25(OH)2D3 might be useful in treatment of
      weakness seen in association with CC.

PMID- 29366787
TI  - RK1, the first very short peptide from Buthus occitanus tunetanus inhibits tumor
      cell migration, proliferation and angiogenesis.
AB  - Scorpion toxins have been the subject of many studies which explore their
      pharmacological potential toward diverse molecular targets, known to monitor key
      mechanisms in cancer such as proliferation, migration and angiogenesis. The few
      peptides from scorpion venom that have an anti-tumor effect are generally
      cytotoxic. Herein, we present the first description of a short 14 amino acid
      peptide (called RK1), purified from the venom of Buthus occitanus tunetanus, with
      the particular capabilities, among different other scorpion peptides, to inhibit
      cell proliferation, migration and angiogenesis of U87 (Glioblastoma) and IGR39
      (Melanoma). Moreover, RK1 is a first peptide derived from scorpion venom
      exhibiting a potential anti-tumoral activity with no manifest toxicity. Our
      results suggest that, in terms of its primary structure, RK1 is unique compared
      to a variety of known peptides purified from scorpion venoms. In addition, RK1 is
      the first natural peptide able to abolish completely the proliferation of cancer
      cells. The Chicken chorioallantoic membrane model revealed that RK1 strongly
      inhibits ex-vivo vascular growth. RK1 could open new perspective for the
      pharmaceutical application of short scorpion venom peptides in anticancer
      activity and may represent the first member of a new group of scorpion peptides.

PMID- 29366788
TI  - IL-1R2 deficiency suppresses dextran sodium sulfate-induced colitis in mice via
      regulation of microbiota.
AB  - Ulcerative colitis (UC) is an inflammatory disease of the colon. IL1R2, which
      encodes IL-1 receptor type 2 (IL-1R2), was reported as a risk gene for UC. To
      elucidate the roles of IL-1R2 in the development of colitis, we examined the
      development of dextran sodium sulfate-induced colitis, a mouse model for UC using
      Il1r2-/- mice. We found the severity score of colitis was milder in Il1r2-/- mice
      compared with wild-type (WT) mice when they were housed separately, however the
      severity score was similar when they were housed in a cage. In the separate
      housing condition, relative contents of Actinobacteria and Bacilli in feces of
      Il1r2-/- mice were lower than that of WT mice. Furthermore, IL-1beta induced the
      expression of antimicrobial peptides (AMPs) from colon. Thus, we show that IL-1R2
      is harmful for the development of colitis, because IL-1R2 promotes the growth of
      proinflammatory intestinal microbiota by suppressing IL-1beta-induced AMP
      production.

PMID- 29366789
TI  - Acidification induces OGR1/Ca2+/calpain signaling in gingival fibroblasts.
AB  - Gingivitis, the mildest form of periodontitis, is generally considered a
      consequence of prolonged exposure of the gingiva to periodontal pathogens. On the
      other hand, several epidemiologic reports have suggested that other etiologic
      factors such as oral acidification may also increase the susceptibility of the
      periodontium to destruction. However, the pathologic mechanism underlying the
      effects of oral acidification on the gingiva is still largely unknown. In this
      study, we analyzed molecular pathways mediating the influence of the acidic
      environment on human gingival fibroblasts (HGFs). Acidic extracellular pH caused
      biphasic increase of intracellular Ca2+ level ([Ca2+]i) through activation of
      ovarian cancer G protein-coupled receptor 1, phospholipase C, and Ca2+ release
      from the endoplasmic reticulum, but not through voltage-gated Ca2+ channels or
      extracellular Ca2+ influx via transient receptor potential cation channel
      subfamily V member 1. The acidic environment was also transiently cytotoxic for
      HGFs; however, the activation of pro-apoptotic proteins poly (ADP-ribose)
      polymerase-1 and BAX was not observed. Furthermore, we found that intracellular
      matrix metalloproteinase 1 was consistently upregulated in HGFs grown in regular
      medium, but significantly reduced in the acidic medium, which depended on [Ca2+]i
      increase, lysosomal pH homeostasis, and Ca2+-dependent protease calpain.
      Considering that HGFs, essential for oral wound healing, in the in vitro culture
      system are placed in wound repair-like conditions, our findings provide important
      insights into molecular mechanisms underlying HGF functional impairment and
      chronic damage to the gingiva caused by the acidic intraoral environment.

PMID- 29366790
TI  - Increased circular RNA hsa_circ_0012673 acts as a sponge of miR-22 to promote
      lung adenocarcinoma proliferation.
AB  - Recent reports have indicated that circular RNA (circRNA) may regulate Lung
      adenocarcinoma (LAC) development. Our previous studies showed that
      hsa_circ_0012673 was up-regulated in a circRNA microarray. However, its
      expression level in LAC has not been verified, and the underlying molecular
      mechanisms in LAC are unknown. In this study, we found that the expression of
      hsa_circ_0012673 was up-regulated in LAC tissues compared to pair-matched
      adjacent non-tumor tissues (P = 0.0079), and that the expression level was
      associated with tumour size (P = 0.015). Furthermore, hsa_circ_0012673 was
      primarily localized in the cytoplasm and promoted cell proliferation of LAC cells
      by sponging miR-22, which targeted erb-b2 receptor tyrosine kinase 3 (ErbB3) in
      LAC. Hsa_circ_0012673 promotes LAC proliferation by suppressing miR-22, which
      targets ErbB3.

PMID- 29366791
TI  - Gold nanoparticle-based probes for the colorimetric detection of Mycobacterium
      avium subspecies paratuberculosis DNA.
AB  - Gold nanoparticle (AuNP) is considered to be the most stable metal nanoparticle
      having the ability to be functionalized with biomolecules. Recently, AuNP-based
      DNA detection methods captured the interest of researchers worldwide.
      Paratuberculosis or Johne's disease, a chronic gastroenteritis in ruminants
      caused by Mycobacterium avium subsp. paratuberculosis (MAP), was found to have
      negative effect in the livestock industry. In this study, AuNP-based probes were
      evaluated for the specific and sensitive detection of MAP DNA. AuNP-based probe
      was produced by functionalization of AuNPs with thiol-modified oligonucleotide
      and was confirmed by Fourier-Transform Infrared (FTIR) spectroscopy. UV-Vis
      spectroscopy and Scanning Electron Microscopy (SEM) were used to characterize
      AuNPs. DNA detection was done by hybridization of 10 MUL of DNA with 5 MUL of
      probe at 63  degrees C for 10 min and addition of 3 MUL salt solution. The method
      was specific to MAP with detection limit of 103 ng. UV-Vis and SEM showed
      dispersion and aggregation of the AuNPs for the positive and negative results,
      respectively, with no observed particle growth. This study therefore reports an
      AuNP-based probes which can be used for the specific and sensitive detection of
      MAP DNA.

PMID- 29366792
TI  - The covalently immobilized antimicrobial peptide LL37 acts as a VEGF mimic and
      stimulates endothelial cell proliferation.
AB  - The chemical coupling of growth factors to solid substrates are discussed as an
      alternative to delivery systems. Utilizing entire proteins for this application
      is hampered by safety and stability considerations. Instead, growth factor
      mimicking peptides are of great interest for biomedical applications, such as
      tissue engineering, due to their purity and stability. The human cathelicidin
      derived antimicrobial peptide LL37, beside its microbicidal activity, was shown
      to stimulate endothelial cell growth when used in a soluble form. Here, in a
      novel approach, spacer mediated immobilization, but not direct conjugation of
      LL37, to a gold substrate was shown to result in a pronounced mitogenic effect on
      endothelial cells, comparable to that of soluble vascular endothelial growth
      factor.

PMID- 29366793
TI  - Transjugular liver biopsy after transjugular intrahepatic portosystemic shunt
      (TIPS) or direct intrahepatic portocaval shunt (DIPS): Is it feasible, effective,
      and safe?
AB  - PURPOSE: To evaluate our experience with transjugular liver biopsies (TJLB) in
      patients with previously placed transjugular intrahepatic portosystemic shunt
      (TIPS) or direct intrahepatic portocaval shunt (DIPS). MATERIAL AND METHODS: A
      single-institution retrospective review was performed looking at all TJLBs in
      patients with previously placed TIPS or DIPS over the past seven years. There
      were six men and one woman (mean age 57.9+/-8.8 [SD] years; range: 47-71 years).
      Patient demographics, indications, procedural details, laboratory data,
      complications, and pathology were recorded. Patients with occluded TIPS were
      excluded from this study. RESULTS: Seven TJLBs were performed, five in patients
      who had a TIPS and two who had a DIPS. Of the patients with TIPS, biopsies were
      performed from the same hepatic vein as TIPS in three procedures and from a
      different hepatic vein in two procedures. In DIPS patients, both biopsies were
      performed from the right hepatic vein. The reasons for the transjugular rather
      than the percutaneous approach to liver biopsy included ascites, coagulopathy, or
      need for concurrent TIPS/DIPS evaluation and/or revision. All procedures were
      technically successful with adequate samples obtained. There were no immediate or
      delayed complications. CONCLUSION: Our results suggest that if needed a TJLB can
      safely and effectively be performed in patients with previously placed TIPS or
      DIPS.

PMID- 29366794
TI  - Characteristics and factors associated with nosocomial pneumonia among patients
      undergoing continuous renal replacement therapy (CRRT): A case-control study.
AB  - OBJECTIVES: Continuous renal replacement therapy (CRRT) is a specialized type of
      dialysis. However, the characteristics and factors associated with nosocomial
      pneumonia in patients undergoing CRRT have received little attention to date.
      Therefore, this study investigated the characteristics of and factors
      contributing to nosocomial pneumonia in patients receiving CRRT. METHODS: The
      clinical data of 1160 patients undergoing CRRT during the period January 2008 to
      December 2015 were analyzed retrospectively. Of these 1160 cases, 145 (12.5%)
      were included in the nosocomial pneumonia group, while 1015 were included in the
      control group. RESULTS: The primary pathogen in the 145 cases of nosocomial
      pneumonia in the CRRT patients was Staphylococcus aureus (58.57%); the morbidity
      rate was 12.5%. Multivariate logistic regression analysis revealed that age (odds
      ratio (OR) 2.209), initial curative time (OR 1.960), underlying diseases (OR
      1.820), consciousness disorder (OR 1.616), organ failure (OR 2.154), the Acute
      Physiology and Chronic Health Evaluation II score (APACHE II) (OR 1.186), and the
      Charlson Comorbidity Index score (CCI) (OR 1.278) were risk factors for
      nosocomial pneumonia (all p<0.05). Conversely, the serum white blood cell count
      (OR 0.585), albumin (OR 0.673), and hemoglobin (OR 0.712) levels were protective
      factors (all p<0.05). CONCLUSIONS: Results from this study indicate that by
      modifying risk factors, such as providing adequate nutrition, earlier treatment
      of underlying diseases, and controlling organ failure, the risks associated with
      nosocomial pneumonia may be reduced.

PMID- 29366795
TI  - Documented coronary atherothrombosis as the cause of death in post-discharge
      patients after coronary revascularization.
AB  - BACKGROUND: The contemporary medications for secondary prevention like statins
      and antithrombotic agents are targeting to delay the progression of
      atherothrombosis. However, there is limited data on the relation between death
      and progressive coronary atherothrombosis. This study sought to evaluate what
      proportion of death after coronary revascularization is related to documented
      progressive coronary atherothrombosis. METHODS: We reviewed the detailed causes
      of death among 15,231 patients receiving their first coronary revascularization
      enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2, dividing into two groups;
      13,839 patients with clinical success and without major complication
      (uncomplicated) and the other 1392 patients (complicated). Documented progressive
      coronary atherothrombosis as the cause of death was defined as preceding coronary
      revascularization within 30days before death or irreversible brain damage and/or
      proof of coronary thrombus by autopsy. RESULTS: During the median follow-up of
      5.4years, 2837 patients died with cumulative 5-year incidence of 17.5%. The
      proportions of cardiac/non-cardiovascular death among all-cause death in
      uncomplicated patients and complicated patients were 36.6%/51.5% and 74.2%/17.4%,
      respectively. The numbers of patients died with documented progressive coronary
      atherothrombosis were 41 (1.9% of all-cause death) and 304 (47.3%). The number
      was only 51 (2.1%) among all post-discharge patients. Dominant causes of cardiac
      death in post-discharge patients included heart failure (10.0%) and sudden
      cardiac death (9.1%), both without apparent relation with progressive coronary
      atherothrombosis. CONCLUSIONS: Only about one-third of deaths were cardiac in
      origin during 5-year follow-up in post-discharge patients after coronary
      revascularization. Cardiac death after discharge was very infrequently related to
      documented progressive coronary atherothrombosis.

PMID- 29366796
TI  - Food waste and the food-energy-water nexus: A review of food waste management
      alternatives.
AB  - Throughout the world, much food produced is wasted. The resource impact of
      producing wasted food is substantial; however, little is known about the energy
      and water consumed in managing food waste after it has been disposed. Herein, we
      characterize food waste within the Food-Energy-Water (FEW) nexus and parse the
      differential FEW effects of producing uneaten food and managing food loss and
      waste. We find that various food waste management options, such as waste
      prevention, landfilling, composting, anaerobic digestion, and incineration,
      present variable pathways for FEW impacts and opportunities. Furthermore,
      comprehensive sustainable management of food waste will involve varied mechanisms
      and actors at multiple levels of governance and at the level of individual
      consumers. To address the complex food waste problem, we therefore propose a
      "food-waste-systems" approach to optimize resources within the FEW nexus. Such a
      framework may be applied to devise strategies that, for instance, minimize the
      amount of edible food that is wasted, foster efficient use of energy and water in
      the food production process, and simultaneously reduce pollution externalities
      and create opportunities from recycled energy and nutrients. Characterization of
      FEW nexus impacts of wasted food, including descriptions of dynamic feedback
      behaviors, presents a significant research gap and a priority for future work.
      Large-scale decision making requires more complete understanding of food waste
      and its management within the FEW nexus, particularly regarding post-disposal
      impacts related to water.

PMID- 29366797
TI  - Simultaneous production of oil enriched in omega-3 polyunsaturated fatty acids
      and biodiesel from fish wastes.
AB  - The waste resulted from fish processing industries are discarded into the
      environment around the world, causing environmental pollution. The main problem
      of fish oil extracted from waste is the high content in free fatty acids (FFA)
      which decrease the yield in fatty acids esters during transesterification
      reactions. Therefore, to correct the fish-oil properties, a new environmentally
      friendly heterogeneous superacid catalyst (SO42-/SnO2-ZrO2) was tested in the
      esterification reaction of FFA with ethanol. The catalyst was characterized by
      different techniques (XRD, FT-IR, FT-IR of adsorbed pyridine, BET, SEM-EDX, TGA
      and acidity measurements). The reaction was found to follow a Langmuir
      Hinshelwood (L-H) dual-site mechanism with the novelty that both Bronsted and
      Lewis acid centers participate equally in the esterification reaction. The pre
      treated oil was subjected to transesterification reaction with ethanol over a
      heterogeneous base catalyst and then, the saturated and unsaturated fractions of
      fatty acid ethyl esters (FAEE) were separated using a vacuum rectification unit
      with falling film. The saturated content can be used as biofuel, while the
      unsaturated FAEE are further transesterified with glycerol in order to obtain oil
      with high content in polyunsaturated fatty acids (PUFA). A detailed study of the
      intrinsic kinetic process at the surface of the superacid catalyst and a thorough
      mathematical model of the fixed bed reactor were written and validated by an
      experimental program, designed according to the D-optimal methodology.

PMID- 29366798
TI  - Organic reductants based leaching: A sustainable process for the recovery of
      valuable metals from spent lithium ion batteries.
AB  - It is significant to recover metal values from spent lithium ion batteries (LIBs)
      for the alleviation or prevention of potential risks towards environmental
      pollution and public health, as well as for the conservation of valuable metals.
      Herein a hydrometallurgical process was proposed to explore the possibility for
      the leaching of different metals from waste cathodic materials (LiCoO2) of spent
      LIBs using organics as reductant in sulfuric acid medium. According to the
      leaching results, about 98% Co and 96% Li can be leached under the optimal
      experimental conditions of reaction temperature - 95  degrees C, reaction time -
      120 min, reductive agent dosage - 0.4 g/g, slurry density - 25 g/L, concentration
      of sulfuric acid-3 mol/L in H2SO4 + glucose leaching system. Similar results (96%
      Co and 100% Li) can be obtained in H2SO4 + sucrose leaching system under
      optimized leaching conditions. Despite a complete leaching of Li (~100%), only
      54% Co can be dissolved in the H2SO4 + cellulose leaching system under optimized
      leaching conditions. Finally, different characterization methods, including UV
      Vis, FT-IR, SEM and XRD, were employed for the tentative exploration of reductive
      leaching reactions using organic as reductant in sulfuric acid medium. All the
      leaching and characterization results confirm that both glucose and sucrose are
      effective reductants during leaching, while cellulose should be further degraded
      to organics with low molecular weights to achieve a satisfactory leaching
      performance.

PMID- 29366799
TI  - Gravimetric composition of the rejects coming from the segregation process of the
      municipal recyclable wastes.
AB  - Rejects from selective collection are municipal solid waste (MSW) not used for
      recycling and are, therefore, destined for the landfill in Brazil. Knowledge of
      the composition and generation of this waste is important for strategically
      planning public policies that minimize its generation and its negative
      environmental impacts. However, this portion of MSW is not very well known.
      Therefore, the aim of this study was to analyze the rejects from the sorting
      process of the selective waste collection in the municipality of Blumenau, in the
      State of Santa Catarina, southern Brazil. The studied rejects came from the
      largest cooperative in the city, and its composition was sorted into 17
      categories of 101 samples over the course of one year, with a total of 3893 kg of
      analyzed rejects. The waste collected by the selective collection of the
      municipality was evaluated monthly to determine which part of this quantity
      became rejects and to determine the composition and seasonality of these rejects.
      The study found that 30.5% of the waste sorted by the cooperative was rejected.
      Among these rejects, the presence of materials that could be marketed by the
      cooperative was verified. Hazardous and/or legally prohibited waste were also
      identified, as were organics, construction and demolition waste, health care
      waste, electronics, textiles, footwear, batteries, and bulbs. Seasonal analysis
      indicated a concerning constant generation of health care waste. Aside from that,
      there was an increase in the generation of waste from electrical and electronic
      equipment (EEE) during the Christmas period, when a large part of the population
      discards their EEE. This information is important for the enforcement of the MSW
      management structure as well as for educational campaigns aimed at the correct
      separation of waste that should be sent for selective collection.

PMID- 29366800
TI  - Production of organic fertilizer from olive mill wastewater by combining solar
      greenhouse drying and composting.
AB  - Olive mill wastewater (OMW) is generated during the production of olive oil. Its
      disposal is still a major environmental problem in Mediterranean countries,
      despite the fact that a large number of technologies have been proposed up to
      date. The present work examines for the first time a novel, simple and low-cost
      technology for OMW treatment combining solar drying and composting. In the first
      step, OMW was dried in a chamber inside a solar greenhouse using swine manure as
      a bulking agent. The mean evaporation rate was found to be 5.2 kg H2O/m2/d for a
      drying period of 6 months (February-August). High phenol (75%) and low nitrogen
      (15%) and carbon (15%) losses were recorded at the end of the solar drying
      process. The final product after solar drying was rich in nutrients (N: 27.8
      g/kg, P: 7.3 g/kg, K: 81.6 g/kg) but still contained significant quantities of
      phenols (18.4 g/kg). In order to detoxify the final product, a composting process
      was applied as a second step with or without the use of grape marc as bulking
      agent. Results showed that the use of grape marc as a bulking agent at a volume
      ratio of 1:1 achieved a higher compost temperature profile (60  degrees C) than
      2:1 (solar drying product: grape marc) or no use (solar drying product). The end
      product after the combination of solar drying and composting had the
      characteristics of an organic fertilizer (57% organic carbon) rich in nutrients
      (3.5% N, 1% P, 6.5% K) with quite low phenol content (2.9 g/kg). Finally, the use
      of this product for the cultivation of pepper plants approved its fertility which
      was found similar with commercial NPK fertilizers.

PMID- 29366802
TI  - Non-coding RNAs in the reprogramming of glucose metabolism in cancer.
AB  - Proliferating cancer cells reprogram their metabolic circuitry to thrive in an
      environment deficient in nutrients and oxygen. Cancer cells exhibit a higher rate
      of glucose metabolism than normal somatic cells, which is achieved by switching
      from oxidative phosphorylation to aerobic glycolysis to meet the energy and
      metabolites demands of tumour progression. This phenomenon, which is known as the
      Warburg effect, has generated renewed interest in the process of glucose
      metabolism reprogramming in cancer cells. Several regulatory pathways along with
      glycolytic enzymes are responsible for the emergence of glycolytic dependence.
      Non-coding (nc)RNAs are a class of functional RNA molecules that are not
      translated into proteins but regulate target gene expression. NcRNAs have been
      shown to be involved in various biological processes, including glucose
      metabolism. In this review, we describe the regulatory role of ncRNAs
      specifically, microRNAs and long ncRNAs-in the glycolytic switch and propose that
      ncRNA-based therapeutics can be used to inhibit the process of glucose metabolism
      reprogramming in cancer cells.

PMID- 29366801
TI  - Neural crest development in Xenopus requires Protocadherin 7 at the lateral
      neural crest border.

PMID- 29366803
TI  - Targeting c-Myc: JQ1 as a promising option for c-Myc-amplified esophageal
      squamous cell carcinoma.
AB  - c-Myc amplification-induced cell cycle dysregulation is a common cause for
      esophageal squamous cell carcinoma (ESCC), but no approved targeted drug is
      available so far. The bromodomain inhibitor JQ1, which targets c-Myc, exerts anti
      tumor activity in multiple cancers. However, the role of JQ1 in ESCC remains
      unknown. In this study, we reported that JQ1 had potent anti-proliferative
      effects on ESCC cells in both time- and dose-dependent manners by inducing cell
      cycle arrest at G1 phase, cell apoptosis, and the mesenchymal-epithelial
      transition. Follow-up studies revealed that both c-Myc/cyclin/Rb and PI3K/AKT
      signaling pathways were inactivated by JQ1, as indicated by the downregulation of
      c-Myc, cyclin A/E, and phosphorylated Rb, AKT and S6. Tumor suppression induced
      by JQ1 in c-Myc amplified or highly expressed xenografts was higher than that in
      xenografts with low expression, suggesting its potential role in prediction. In
      conclusion, targeting c-Myc by JQ1 could cause significant tumor suppression in
      ESCC both in vitro and in vivo. Also, c-Myc amplification or high expression
      might serve as a potential biomarker and provide a promising therapeutic option
      for ESCC.

PMID- 29366804
TI  - Clinical utility of non-EpCAM based circulating tumor cell assays.
AB  - Methods enabling the isolation, detection, and characterization of circulating
      tumor cells (CTCs) in blood have clear potential to facilitate precision medicine
      approaches in patients with cancer, not only for prognostic purposes but also for
      prediction of the benefits of specific therapies in oncology. However, current
      CTC assays, which capture CTCs based on expression of epithelial cell adhesion
      molecule (EpCAM), fail to capture cells from de-differentiated tumors and
      carcinomas undergoing loss of the epithelial phenotype during the
      invasion/metastatic process. To address this limitation, many groups are
      developing non-EpCAM based CTC assays that incorporate nanotechnology to improve
      test sensitivity for rare but important cells that may otherwise go undetected,
      and therefore may improve upon clinical utility. In this review, we outline
      emerging non-EpCAM based CTC assays utilizing nanotechnology approaches for CTC
      capture or characterization, including dendrimers, magnetic nanoparticles, gold
      nanoparticles, negative selection chip or software-based on-slide methods, and
      nano-scale substrates. In addition, we address challenges that remain for the
      clinical translation of these platforms.

PMID- 29366805
TI  - Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice.
AB  - The C1q/TNF-related protein 6 (CTRP6) is an adipokine involved in diverse
      biological processes. Formerly, we identified that CTRP6 regulates adipocyte
      differentiation, fatty acid oxidation and triglyceride accumulation in vitro.
      However, the effects of CTRP6 on adiposity in vivo have not yet been defined.
      This study aimed to confirm the involvement of CTRP6 in adipose accumulation and
      brown adipogenesis by intraperitoneal injection of the CTRP6-shRNA lentivirus
      into mice (CL mice). CL mice were significantly thinner than the control mice
      after feeding with a high fat diet (HFD), independent of food intake quantity.
      These HFD-fed CL mice displayed lower white and brown adipocyte sizes, and serum
      leptin levels, but an increase in serum adiponectin and insulin sensitivity
      relative to control mice. Additionally, the brown fat markers, such as UCP1,
      PRDM16, PGC1alpha and Cidea were found to be upregulated in the white and brown
      adipose tissue of the CL mice. These markers were also upregulated in a primary
      culture of mouse white and brown adipocytes treated with the CTRP6-shRNA
      lentivirus. Mechanistically, the knockdown of CTRP6 increased p38MAPK
      phosphorylation, but decreased expression of proteins involved in the Hedgehog
      signaling pathway (Sufu, Gli2 and Gli3). CTRP6 knockdown also upregulated
      expression of mitochondrial metabolic factors NRF-1, TFAM, CPT1 and Cyt C. Data
      from the current study show that CTRP6 knockdown protects against diet-induced
      obesity and promotes brown adipogenesis by the p38MAPK/Hh signaling pathway in
      conjunction with the upregulation of brown fat markers and mitochondrial
      metabolic factors.

PMID- 29366806
TI  - Silencing of Kangai 1 C-terminal interacting tetraspanin suppresses progression
      of cholangiocarcinoma.
AB  - Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. CC
      treatment options are very limited especially for patients with distant
      metastasis. Kangai 1 C-terminal interacting tetraspanin (KITENIN) is highly
      expressed in numerous cancers, but the role of KITENIN in CC remains unknown.
      Here, we have investigated for the first time the function of KITENIN in human CC
      cell lines (TFK-1, SZ-1), tissues and a CC mouse model (Alb-Cre/LSL
      KRASG12D/p53L/L). KITENIN was expressed in 92.2% of human CC tissues, in murine
      CC samples and also in human CC cell lines. Knockdown of KITENIN by small
      interfering RNA (siRNA) effectively reduced proliferation, migration, invasion
      and colony formation in both intra- and extra-hepatic CC cells. The expression of
      epithelial-mesenchymal transition (EMT) markers like N-cadherin, Vimentin, Snail
      and Slug were suppressed in KITENIN knockdown CC cells. Our results indicate that
      KITENIN is crucial for cholangiocarcinogenesis and it might become a potential
      therapeutic target for human CC treatment.

PMID- 29366807
TI  - Bioactivity and gene expression profiles of hiPSC-generated retinal ganglion
      cells in MT-ND4 mutated Leber's hereditary optic neuropathy.
AB  - Leber's hereditary optic neuropathy (LHON) is the maternally inherited
      mitochondrial disease caused by homoplasmic mutations in mitochondrial electron
      transport chain Complex I subunit genes. The mechanism of its incomplete
      penetrance is still largely unclear. In this study, we created the patient
      specific human induced pluripotent stem cells (hiPSCs) from MT-ND4 mutated LHON
      affected patient, asymptomatic mutation carrier and healthy control, and
      differentiated them into retinal ganglion cells (RGCs). We found the defective
      neurite outgrowth in affected RGCs, but not in the carrier RGCs which had
      significant expression of SNCG gene. We observed enhanced mitochondrial
      biogenesis in affected and carrier derived RGCs. Surprisingly, we observed
      increased NADH dehydrogenase enzymatic activity of Complex I in hiPSC-derived
      RGCs of asymptomatic carrier, but not of the affected patient. LHON mutation
      substantially decreased basal respiration in both affected and unaffected carrier
      hiPSCs, and had the same effect on spare respiratory capacity, which ensures
      normal function of mitochondria in conditions of increased energy demand or
      environmental stress. The expression of antioxidant enzyme catalase was decreased
      in affected and carrier patient hiPSC-derived RGCs as compared to the healthy
      control, which might indicate to higher oxidative stress-enriched environment in
      the LHON-specific RGCs. Microarray profiling demonstrated enhanced expression of
      cell cycle machinery and downregulation of neuronal specific genes.

PMID- 29366808
TI  - Primate-specific miRNA-637 inhibited tumorigenesis in human pancreatic ductal
      adenocarcinoma cells by suppressing Akt1 expression.
AB  - As a primate-specific microRNA, miR-637 has been discovered for nearly 10 years.
      Our previous study demonstrated that miR-637 acted as a suppressor in
      hepatocellular carcinoma. However, its biomedical significance in pancreatic
      cancer remains obscure. In the present study, miR-637 was found to be
      significantly downregulated in pancreatic ductal adenocarcinoma (PDAC) cell lines
      and most of the PDAC specimens. Furthermore, the enforced overexpression of miR
      637 dramatically inhibited cell proliferation and induced apoptosis of PDAC
      cells. Akt1, as a serine/threonine-protein kinase, has been identified as an
      oncogene in multiple cancers including pancreatic cancer. Our data confirmed that
      Akt1 was a novel target for miR-637, and its knockdown also induced cell growth
      inhibition and apoptosis in PDAC cells. In conclusion, our data indicated that
      miR-637 acted as a tumor-suppressor in PDAC, and the suppressive effect was
      mediated, at least partially, by suppressing Akt1 expression.

PMID- 29366809
TI  - In vitro analysis of the transcriptional regulatory mechanism of zebrafish
      pou5f3.
AB  - Zebrafish pou5f3 (previously named pou2), a close homologue of mouse Oct4,
      encodes a PouV-family transcription factor. pou5f3 has been implicated in diverse
      aspects of developmental regulation during embryogenesis. In the present study,
      we addressed the molecular function of Pou5f3 as a transcriptional regulator and
      the mechanism by which pou5f3 expression is transcriptionally regulated. We
      examined the influence of effector genes on the expression of the luciferase gene
      under the control of the upstream 2.1-kb regulatory DNA of pou5f3 (Luc-2.2) in
      HEK293T and P19 cells. We first confirmed that Pou5f3 functions as a
      transcriptional activator both in cultured cells and embryos, which confirmed
      autoregulation of pou5f3 in embryos. It was further shown that Luc-2.2 was
      activated synergistically by pou5f3 and sox3, which is similar to the co
      operative activity of Oct4 and Sox2 in mice, although synergy between pou5f3 and
      sox2 was less obvious in this zebrafish system. The effects of pou5f3 deletion
      constructs on the regulation of Luc-2.2 expression revealed different roles for
      the three subregions of the N-terminal region in Pou5f3 in terms of its
      regulatory functions and co-operativity with Sox3. Electrophoretic mobility shift
      assays confirmed that Pou5f3 and Sox3 proteins specifically bind to adjacent
      sites in the 2.1-kb DNA and that there is an interaction between the two
      proteins. The synergy with sox3 was unique to pou5f3-the other POU factor genes
      examined did not show such synergy in Luc-2.2 regulation. Finally, functional
      interaction was observed between pou5f3 and sox3 in embryos in terms of the
      regulation of dorsoventral patterning and convergent extension movement. These
      findings together demonstrate co-operative functions of pou5f3 and sox3, which
      are frequently coexpressed in early embryos, in the regulation of early
      development.

PMID- 29366810
TI  - Ruta graveolens water extract inhibits cell-cell network formation in human
      umbilical endothelial cells via MEK-ERK1/2 pathway.
AB  - Angiogenesis is a process encompassing several steps such as endothelial cells
      proliferation, differentiation and migration to form a vascular network,
      involving different signal transduction pathways. Among these, ERK1/2 signaling
      mediates VEGF-dependent signaling pathway. Here we report that the water extract
      of Ruta graveolens (RGWE), widely known as a medicinal plant, is able to impair
      in a dose-dependent manner, cell network formation without affecting cell
      viability. Biochemical analysis showed that the major component of RGWE is rutin,
      unable to reproduce RGWE effect. We found that RGWE inhibits ERK1/2
      phosphorylation and that this event is crucial in cell network formation since
      the transfection of HUVEC with a constitutively active MEK (caMEK), the ERK1/2
      activator, induces a robust cell network formation as compared to untransfected
      and/or mock transfected cells and, more importantly, caMEK transfected cells
      became unresponsive to RGWE. Moreover, RGWE inhibits VEGF and nestin gene
      expression, necessary for vessel formation, and the caMEK transfection induces
      their higher expression. In conclusion, we report that RGWE is able to
      significantly impair vessels network formation without affecting cell viability,
      preventing ERK1/2 activation and, in turn, down-regulating VEGF and nestin
      expression. These findings point to RGWE as a potential therapeutic tool capable
      to interfere with pathologic angiogenesis.

PMID- 29366811
TI  - Plant membrane trafficking is coming of age.

PMID- 29366812
TI  - An updated view on the functions of caspases in inflammation and immunity.
AB  - The binary classification of mammalian caspases as either apoptotic or
      inflammatory is now obsolete. Emerging data indicate that all mammalian caspases
      are intricately involved in the regulation of inflammation and immunity. They
      participate in embryonic and adult tissue homeostasis, control leukocyte
      differentiation, activation and effector functions, and mediate innate and
      adaptive immunity signaling. Caspases also promote host resistance by regulating
      anti-oxidant defense and pathogen clearance through regulation of phagosomal
      maturation, actin dynamics and phagosome-lysosome fusion. Beyond apoptosis, they
      regulate inflammatory cell death, eliciting rapid pyroptosis of infected cells,
      while inhibiting necroptosis-mediated tissue destruction and chronic
      inflammation. In this review, we describe the cellular and molecular mechanisms
      underlying non-apoptotic functions of caspases in inflammation and immunity and
      provide an updated view of their functions as central regulators of tissue
      homeostasis and host defense.

PMID- 29366813
TI  - Anatomic mesohepatectomy versus extended hepatectomy for patients with centrally
      located hepatocellular carcinoma.
AB  - BACKGROUND: Both mesohepatectomy (MH) and extended hepatectomy (EH) can be
      performed for centrally located hepatocellular carcinoma (HCC). In this study,
      the long-term prognosis of these surgical approaches was assessed in patients
      with HCC. METHODS: A retrospective review was undertaken of 171 HCC patients who
      underwent anatomic hepatectomy for centrally located HCC between January 2005 and
      January 2016 in West China Hospital, Sichuan University. The impact of the
      surgical methods on prognosis was assessed for these patients by multivariable
      regression analysis. In addition, the patients in the MH group were matched in a
      1:2 ratio with EH controls. RESULTS: In non-adjusted models, patients in the MH
      group had similar overall survival (OS, p = 0.066) and disease free survival
      (DFS, p = 0.654) compared to EH patients. After adjusting for all identified
      confounders, MH patients showed better OS in comparison with patients in the EH
      group (p = 0.001), while the DFS was similar. In the propensity score-matched
      (PSM) subset, patients in MH group had better OS (p = 0.033) but similar DFS (p =
      0.328) compared to patients in the EH group. CONCLUSION: Anatomic MH can be
      recommended as a reasonable surgical option in selected patients with centrally
      located HCC.

PMID- 29366814
TI  - Tumor manipulation during pancreatic resection for pancreatic cancer induces
      dissemination of tumor cells into the peritoneal cavity: a systematic review.
AB  - BACKGROUND: Intraoperative tumor manipulation may induce the dissemination of
      occult peritoneal tumor cells (OPTC) into the peritoneal cavity. METHODS: A
      systematic review was performed in the PubMed, Embase and Cochrane databases from
      inception to March 15, 2017. Eligible were studies that analyzed the presence of
      OPTC in peritoneal fluid, by any method, both before and after resection in
      adults who underwent intentionally curative pancreatic resection for
      histopathologically confirmed pancreatic ductal adenocarcinoma in absence of
      macroscopic peritoneal metastases. RESULTS: Four studies with 138 patients met
      the inclusion criteria. The pooled rate of OPTC prior to tumor manipulation was
      8% (95% CI 2%-24%). The pooled detection rate of OPTC in patients in whom OPTC
      became detectable only after tumor manipulation was 33% (95% CI 15-58%). Only one
      study (28 patients) reported on survival, which was worse in patients with OPTC
      (median 11.1 months versus 30.3 months; p = 0.030). CONCLUSION: This systematic
      review suggests that tumor manipulation induces OPTC in one third of patients
      with pancreatic cancer. Since data on survival are lacking, future studies should
      determine the prognostic consequences of tumor manipulation, including the
      potential therapeutic effect of 'no-touch' and minimally invasive resection
      strategies.

PMID- 29366815
TI  - Systematic review on the role of serum tumor markers in the detection of
      recurrent pancreatic cancer.
AB  - BACKGROUND: Biomarker testing can be helpful to monitor disease progression after
      resection of pancreatic cancer. This systematic review aims to give an overview
      of the literature on the diagnostic value of serum tumor markers for the
      detection of recurrent pancreatic cancer during follow-up. METHODS: A systematic
      search was performed to 2 October 2017. All studies reporting on the diagnostic
      value of postoperatively measured serum biomarkers for the detection of
      pancreatic cancer recurrence were included. Data on diagnostic accuracy of tumor
      markers were extracted. Forest plots and pooled values of sensitivity and
      specificity were calculated. RESULTS: Four articles described test results of CA
      19-9. A pooled sensitivity and specificity of respectively 0.73 (95% CI 0.66
      0.80) and 0.83 (95% CI 0.73-0.91) were calculated. One article reported on CEA,
      showing a sensitivity of 50% and specificity of 65%. No other serum tumor markers
      were discussed for surveillance purposes in the current literature. CONCLUSION:
      Although testing of serum CA 19-9 has considerable limitations, CA 19-9 remains
      the most used serum tumor marker for surveillance after surgical resection of
      pancreatic cancer. Further studies are needed to assess the role of serum tumor
      marker testing in the detection of recurrent pancreatic cancer and to optimize
      surveillance strategies.

PMID- 29366816
TI  - Robotic pancreatoduodenectomy at an experienced institution is not associated
      with an increased risk of post-pancreatic hemorrhage.
AB  - BACKGROUND: Postpancreatectomy hemorrhage (PPH) is a serious and life threatening
      complication following pancreaticoduodenectomy. The objective was to determine
      whether PPH incidence is elevated in a series of robotic pancreatoduodenectomy
      (RPD) from a high-volume institution and if video review can identify technical
      factors associated with PPH. METHODS: A retrospective review of RPDs from October
      2008 to March 2016 was performed. PPH was classified by established international
      criteria. Technical factors from RPD resection were ascertained using video
      analysis. Clinical and technical variables were analyzed using multivariate
      analysis. RESULTS: Of 400 patients who underwent RPD PPH occurred in 19 (4.8%)
      and 168 (42%) had videos available to review. The technique of RPD was consistent
      but a falciform flap was performed routinely after RPD#181 and flaps were
      performed less (37.5% vs 75%) in the pseudoaneurysm group (p = 0.033). On
      univariate analysis of technical variables, gastroduodenal artery (GDA)
      mishandling and suture ligation were positive predictors of pseudoaneurysm
      formation while falciform flap placement was a negative predictor (all p < 0.05).
      GDA suture ligation remained significant on multivariate analysis (p = 0.006). A
      negative relationship was found between pseudoaneurysm occurrence and time (rho =
      -0.533; p < 0.05). CONCLUSIONS: PPH in a large series of RPD is similar to
      reported rates in historical open control series; however, pseudoaneurysm is less
      common with increasing experience. Video review is a useful tool in identifying
      technical variables during in RPD.

PMID- 29366817
TI  - Gas exchanges in children with cystic fibrosis or primary ciliary dyskinesia: A
      retrospective study.
AB  - Primary ciliary dyskinesia (PCD) and cystic fibrosis (CF) both entail
      bronchiectasis and pulmonary impairment as measured using spirometry, during
      childhood. We aimed at looking whether blood gas exchanges progressed differently
      between CF and PCD children in a retrospective study of repeated measurements.
      Comparisons between groups (Wilcoxon-Mann-Whitney and Chi-squared tests) and a
      mixed linear model, adjusted for age, evaluated associations between diseases and
      PaO2, PaCO2, or PaO2-PaCO2 ratio. Among 42 PCD and 73 CF children, 62% and 59%
      had respectively bronchiectasis (P = 0.75). Spirometry and blood gases were
      similar at inclusion (PaO2 median [IQR] PCD -1.80 [-3.40; -0.40]; CF -1.80 [
      4.20; 0.60] z-scores; P = 0.72). PaO2 and PaO2-PaCO2 ratio similarly and
      significantly decreased with age in both groups (P < 0.01) whereas PaCO2
      increased more in CF (P = 0.02) remaining within the range of normal (except for
      one child). To conclude, gas exchange characteristics, similarly initially
      impaired in PCD and CF children, tended to less deteriorate with time in PCD
      children who could benefit from an early diagnosis.

PMID- 29366818
TI  - Social and environmental determinants of physical activity in urban parks:
      Testing a neighborhood disorder model.
AB  - The current study examined the nexus of neighborhood disorder-in the form of
      physical disorder (e.g., broken glass and vandalism) and social disorder (e.g.,
      public drinking and lewd conduct)-and physical activity (PA) in urban public
      parks to inform public policy addressing chronic disease in at-risk populations.
      Five hundred and twenty-two unique observations were conducted in 22 public parks
      from March to September 2016. The study utilized the System for Observing Play
      and Recreation in Communities (SOPARC) to document age, gender, ethnicity, and PA
      level of park users. The Physical Activity Resource Assessment (PARA) was used to
      document observed physical and social disorder incivilities in public parks
      included in the current study. Males, adults, and Latina/os accounted for the
      largest number of park users, respectively. Significant PA differences were
      observed across gender, age, and ethnicity. Multiple linear regression
      controlling for gender, age, and ethnicity found physical disorder, but not
      social disorder, generally predicted PA reductions. While it has been
      demonstrated that physical disorder predicts PA reductions in low-income
      communities of color, this is the first study to reveal that physical disorder
      may lead to decreased PA in urban public parks. Thus, remediation of public park
      incivilities characterized by physical disorder, paired with community outreach,
      may lead to increased PA in at-risk communities.

PMID- 29366819
TI  - Thirty-day smoking in adolescence is a strong predictor of smoking in young
      adulthood.
AB  - Thirty-day smoking, although a widely used measure of adolescent smoking (age 12
      16), has been questioned as an accurate measure of young adult (age 26-30)
      smoking behavior, particularly when critiquing studies linking use of e
      cigarettes with subsequent cigarette smoking. We used logistic regression to test
      two measures of 30-day adolescent smoking as predictors of young adult smoking in
      the National Longitudinal Survey of Youth 1997. Adjusting for psychosocial
      covariates, compared to those who smoked zero days in the past 30 days in
      adolescence, odds of any past-30-day smoking in young adulthood ranged from 2.85
      (95% CI: 1.85-4.37) for those who smoked 1 day to 4.81 (3.50-6.59) for those who
      smoked daily as adolescents, and adjusted odds of daily smoking in young
      adulthood ranged from 1.99 (1.24-3.18) to 4.69 (3.42-6.43). Compared with
      adolescent never smokers, adjusted odds of any past-30-day smoking in young
      adulthood among adolescent former smokers was 2.11 (1.77-2.53), and among
      adolescent current smokers, ranged from 3.03 (2.22-4.14) for those who smoked 1-5
      cigarettes per month to 8.19 (5.80-11.55) for those who smoked daily. Adjusted
      odds of daily smoking in young adulthood were 2.49 (2.12-2.91) for adolescent
      former smokers and, among adolescent current smokers, ranged from 2.54 (1.92
      3.37) for those who smoked 1-5 cigarettes per month to 8.65 (6.06-12.35) for
      those who smoked daily. There is a strong dose-response relationship between 30
      day smoking in adolescence-even a single day in the month-and 30-day and daily
      smoking in young adulthood.

PMID- 29366820
TI  - Alcohol use patterns and risk of diabetes onset in the 1979 National Longitudinal
      Survey of Youth Cohort.
AB  - One of the major limitations in studying alcohol's effect on risk for diabetes is
      the issue of classifying drinking patterns across the life course prior to the
      onset of diabetes. Furthermore, this research often overlooks important life
      course risk factors such as obesity and early-life health problems that may
      complicate estimation of the relationship between alcohol and diabetes. This
      study used data from the US National Longitudinal Survey of Youth 1979 cohort of
      14-21 year olds followed through 2012 (n = 8289). Alcohol use was captured
      through time-varying measures of past month volume and frequency of days with 6+
      drinks. Discrete-time survival models controlling for demographics, early-life
      characteristics and time-varying risk factors of employment, smoking, and body
      mass index (BMI) group, stratified by sex and race/ethnicity, were estimated.
      Increased odds of diabetes onset was found among lifetime abstainers for women
      compared to the low volume reference group (odds ratio (OR) 1.57; 95% Confidence
      Interval (CI) 1.07-2.3). Increased odds of diabetes onset was also found among
      women who reported drinking 6+ drinks in a day on a weekly basis during the prior
      10 years (OR 1.55; CI 1.04-2.31). Models interacting alcohol and BMI groups found
      increased odds of diabetes onset from lifetime abstention among overweight women
      only (OR 3.06; CI 1.67-5.60). This study confirms previous findings of protective
      effects from low volume drinking compared to lifetime abstention and harmful
      effects from regular heavy occasion drinking for women. Further, protective
      effects in this US sample were found to be limited to overweight women only.

PMID- 29366821
TI  - A Rho-GTPase based model explains spontaneous collective migration of neural
      crest cell clusters.
AB  - We propose a model to explain the spontaneous collective migration of neural
      crest cells in the absence of an external gradient of chemoattractants. The model
      is based on the dynamical interaction between Rac1 and RhoA that is known to
      regulate the polarization, contact inhibition and co-attraction of neural crest
      cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and
      RhoA on the cell membrane with a mechanical model for the overdamped motion of
      membrane vertices, we show that co-attraction and contact inhibition cooperate to
      produce persistence of polarity in a cluster of neural crest cells by suppressing
      the random onset of Rac1 hotspots that may mature into new protrusion fronts.
      This produces persistent directional migration of cell clusters in corridors. Our
      model confirms a prior hypothesis that co-attraction and contact inhibition are
      key to spontaneous collective migration, and provides an explanation of their
      cooperative working mechanism in terms of Rho GTPase signaling. The model shows
      that the spontaneous migration is more robust for larger clusters, and is most
      efficient in a corridor of optimal confinement.

PMID- 29366822
TI  - Performance limits and trade-offs in entropy-driven biochemical computers.
AB  - It is now widely accepted that biochemical reaction networks can perform
      computations. Examples are kinetic proof reading, gene regulation, or signalling
      networks. For many of these systems it was found that their computational
      performance is limited by a trade-off between the metabolic cost, the speed and
      the accuracy of the computation. In order to gain insight into the origins of
      these trade-offs, we consider entropy-driven computers as a model of biochemical
      computation. Using tools from stochastic thermodynamics, we show that entropy
      driven computation is subject to a trade-off between accuracy and metabolic cost,
      but does not involve time-trade-offs. Time trade-offs appear when it is taken
      into account that the result of the computation needs to be measured in order to
      be known. We argue that this measurement process, although usually ignored, is a
      major contributor to the cost of biochemical computation.

PMID- 29366823
TI  - Data-driven modelling of social forces and collective behaviour in zebrafish.
AB  - Zebrafish are rapidly emerging as a powerful model organism in hypothesis-driven
      studies targeting a number of functional and dysfunctional processes.
      Mathematical models of zebrafish behaviour can inform the design of experiments,
      through the unprecedented ability to perform pilot trials on a computer. At the
      same time, in-silico experiments could help refining the analysis of real data,
      by enabling the systematic investigation of key neurobehavioural factors. Here,
      we establish a data-driven model of zebrafish social interaction. Specifically,
      we derive a set of interaction rules to capture the primary response mechanisms
      which have been observed experimentally. Contrary to previous studies, we include
      dynamic speed regulation in addition to turning responses, which together provide
      attractive, repulsive and alignment interactions between individuals. The
      resulting multi-agent model provides a novel, bottom-up framework to describe
      both the spontaneous motion and individual-level interaction dynamics of
      zebrafish, inferred directly from experimental observations.

PMID- 29366824
TI  - Temperature-driven population abundance model for Culex pipiens and Culex
      restuans (Diptera: Culicidae).
AB  - We develop a temperature-driven abundance model for West Nile virus (WNV) vector
      species, Culex pipiens and Culex restuans. Temperature-dependent response
      functions for mosquito development, mortality, and diapause were formulated based
      on results from available laboratory and field studies. Numerical results
      compared to observed mosquito trap counts from 2004-2016 demonstrate the ability
      of our model to predict the observed trend of the mosquito population over a
      single season in the Peel Region, Ontario. The model has potential to be used as
      a real-time mosquito abundance forecasting tool with applications in mosquito
      control programs.

PMID- 29366825
TI  - Electrical stimulation or MK-801 in the inferior colliculus improve motor
      deficits in MPTP-treated mice.
AB  - The inferior colliculus (IC) is an important midbrain relay station for the
      integration of descending and ascending auditory information. Additionally, the
      IC has been implicated in processing sensorimotor responses. Glutamatergic and
      GABAergic manipulations in the IC can improve motor deficits as demonstrated by
      the animal model of haloperidol-induced catalepsy. However, how the IC influences
      motor function remains unclear. We investigated the effects of either
      intracollicular deep brain stimulation (DBS) or microinjection of the
      glutamatergic antagonist MK-801 or the agonist NMDA in C57BL/6J mice chronically
      treated with saline or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). After
      DBS or microinjections, the mice were submitted to rotarod and open field tests,
      respectively. DBS in the IC was effective to increase the time spent on the
      rotarod in MPTP-treated mice. After unilateral microinjection of MK-801, but not
      NMDA, MPTP-treated mice increased the distance travelled in the open field (p <
      0.05). In conclusion, intracollicular DBS or MK-801 microinjection can improve
      motor performance in parkinsonian mice suggesting the IC as a new and non
      conventional therapeutic target in motor impairment.

PMID- 29366826
TI  - Concurrent PTHrp- and calcitriol-mediated hypercalcemia associated with
      cholangiocarcinoma.

PMID- 29366827
TI  - Gastric ulcer related with gastrostomy feeding tube: Description of 3 cases and
      review of literature.

PMID- 29366828
TI  - Classification of lumbopelvic-hip complex instability on kinematics amongst
      female team handball athletes.
AB  - OBJECTIVES: The purpose of this study was to examine how lumbopelvic-hip complex
      (LPHC) stability, via knee valgus, affects throwing kinematics during a team
      handball jump shot. DESIGN: LPHC stability was classified using the value of knee
      valgus at the instant of landing from the jump shot. If a participant displayed
      knee valgus of 17 degrees  or greater, they were classified as LPHC unstable.
      Stable and unstable athletes' throwing mechanics were compared. METHODS: Twenty
      female team handball athletes (26.5+/-4.7years; 1.75+/-0.04m; 74.4+/-6.4kg;
      experience level: 4.8+/-4.1 years) participated. An electromagnetic tracking
      system was used to collect kinematic data while participants performed three 9-m
      jump shots. The variables considered were kinematics of the pelvis, trunk, and
      shoulder; and segmental speeds of the pelvis, torso, humeral, forearm, and ball
      velocities. Data were analyzed across four events: foot contact, maximum shoulder
      external rotation, ball release, and maximum shoulder internal rotation. RESULTS:
      Statistically significant differences were found between groups in pelvis, trunk,
      humerus, and forearm velocities at all events (p<=0.05). Specifically, the
      unstable group displayed significantly slower speeds. CONCLUSIONS: These findings
      suggest the difference in throwing mechanics are affected by LPHC instability for
      this select group of female team handball athletes. These differences infer an
      increased risk of injury in the upper and lower extremities when landing from a
      jump shot because of the energy losses throughout the kinetic chain and lack of
      utilization of the entire chain. It is recommended that further investigations
      also consider muscle activation throughout the throwing motion.

PMID- 29366829
TI  - A revised dated phylogeny of scorpions: Phylogenomic support for ancient
      divergence of the temperate Gondwanan family Bothriuridae.
AB  - The scorpion family Bothriuridae occupies a subset of landmasses formerly
      constituting East and West temperate Gondwana, but its relationship to other
      scorpion families is in question. Whereas morphological data have strongly
      supported a sister group relationship of Bothriuridae and the superfamily
      Scorpionoidea, a recent phylogenomic analysis recovered a basal placement of
      bothriurids within Iurida, albeit sampling only a single exemplar. Here we
      reexamined the phylogenetic placement of the family Bothriuridae, sampling six
      bothriurid exemplars representing both East and West Gondwana, using
      transcriptomic data. Our results demonstrate that the sister group relationship
      of Bothriuridae to the clade ("Chactoidea" + Scorpionoidea) is supported by the
      inclusion of additional bothriurid taxa, and that this placement is insensitive
      to matrix completeness or partitioning by evolutionary rate. We also estimated
      divergence times within the order Scorpiones using multiple fossil calibrations,
      to infer whether the family Bothriuridae is sufficiently old to be characterized
      as a true Gondwanan lineage. We show that scorpions underwent ancient
      diversification between the Devonian and early Carboniferous. The age interval of
      the bothriurids sampled (a derived group that excludes exemplars from South
      Africa) spans the timing of breakup of temperate Gondwana.

PMID- 29366830
TI  - Integrative Regulation of Drought Escape through ABA-Dependent and -Independent
      Pathways in Rice.
AB  - Many plants have evolved a drought escape (DE) mechanism to shorten their life
      cycle when facing water-deficit conditions. While drought tolerance has been
      intensively investigated, the genetic and molecular mechanisms of DE remain
      elusive. In this study, we found that low water-deficit treatment (LWT) at the
      early stage of rice development can trigger early flowering and reduced tiller
      numbers. LWT induced the accumulation of abscisic acid (ABA), which in turn has
      feed-back effects on light perception and circadian clock by synchronously
      regulating many flowering-related genes to promote early flowering. Moreover,
      some of light receptors, circadian components, and flowering-related genes
      including OsTOC1, Ghd7, and PhyB were found to be involved in LWT in an ABA
      dependent manner, whereas some of the other flowering-related genes including
      OsGI, OsELF3, OsPRR37, and OsMADS50 were involved in the regulation of DE
      independent of ABA. In addition, we found that strigolactones and OsTB1 are
      involved in the tillering inhibition under LWT, which is independent of the
      flowering pathway in rice. Taken together, our findings provide compelling
      evidence that DE in rice is coordinately regulated by multiple pathways during
      the reproduction (flowering) switch.

PMID- 29366831
TI  - Predictive value of serum soluble corin in the risk of hyperglycemia: A
      population-based prospective cohort study in China.
AB  - BACKGROUND: Serum soluble corin has been suggested to be associated with
      hyperglycemia by cross-sectional study. However, the prospective relationship
      between them remains unclear, and whether lipid component influences the
      relationship between them has not yet been studied. METHODS: A total of 1961
      participants who were free from hyperglycemia were enrolled at baseline in 2010.
      The serum soluble corin concentrations were measured at baseline and all
      participants were followed up for hyperglycemia in 2014. RESULTS: The association
      between serum soluble corin and hyperglycemia incidence was appreciably modified
      by high density lipoprotein cholesterol (HDL-C) (Pinteraction = 0.04). Elevated
      serum soluble corin was associated with the risk of hyperglycemia only in the HDL
      C >=1.04 mmol/l subgroup rather than all participants. In participants with HDL-C
      >=1.04 mmol/l, the adjusted odds ratio (95% CU) of hyperglycemia associated with
      the fourth quartiles of corin was 1.78 (1.08-2.94) compared with the lowest
      quartile of serum soluble corin, and there was a positive linear dose-response
      relationship between them (P for linearity <0.01). The ordinal analysis showed an
      association between serum soluble corin and hyperglycemia severity (adjusted OR,
      1.81; 95% CI, 1.10-2.99; Ptrend = 0.02, when 2 extreme quartiles were compared).
      The addition of serum soluble corin to conventional risk factors improved risk
      prediction for hyperglycemia (net reclassification index: 0.16; integrated
      discrimination improvement: 0.01) in participants with HDL-C >=1.04 mmol/l.
      CONCLUSION: Serum soluble corin might be a valuable biomarker in prediction of
      future hyperglycemia in population with HDL-C >=1.04 mmol/l, suggesting that
      corin might play a potential role in glucose metabolism.

PMID- 29366832
TI  - Two de novo variations identified by massively parallel sequencing in 13 Chinese
      families with children diagnosed with autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a genetically heterogeneous neurodevelopmental
      disorder characterized by impairments in social interaction and communication,
      and by restricted and repetitive behaviors. The genetic architecture of ASD has
      been elucidated, including chromosomal rearrangements, de novo or inherited rare
      variants, and copy number variants. However, the genetic mechanism of Chinese
      families with ASD children is explored rarely. To identify genetic pathogenesis,
      we performed massively parallel sequencing on 13 Chinese ASD trio families, and
      found two de novo variations. The novel de novo splice alteration c.664 + 2T > G
      in the DEAF1 gene and the novel de novo missense mutation c.95 C > T in the AADAT
      gene associated with ASD may be important clues for exploring the etiology of
      this disorder.

PMID- 29366833
TI  - Promising alternatives for one-tier testing of Lyme borreliosis.
AB  - A main focus of human health studies is the early detection of infectious
      diseases to enable more rapid treatment and prevent disease transmission.
      Diagnosis of Lyme borreliosis has been always challenging because of the lack of
      specific, but simple assay formats. Two-tiered testing has been recommended by US
      Centers for Disease Control and Prevention to provide more specific results for
      diagnosis of Lyme disease. However, such a technique is time consuming and is not
      well suited for early stage detection. Therefore, many tests were proposed as
      alternatives to overcome these drawbacks. Simple assays, which are mainly
      performed in one-tier manner, could be conducted with better performance than the
      two-tiered testing. Proposed assays utilize both newly identified antigens and
      new platforms to improve detection performance. These assays can be classified
      into those based on employing a single antigen and assays based on using multiple
      antigens. In addition to assays to this type of assays, immunoassays on
      borreliosis-related biomarkers are available. We report here the most recent
      assays developed over the last 10 years, for detection of Lyme borreliosis in
      body fluids.

PMID- 29366834
TI  - The cardiac troponin response following physical exercise in relation to
      biomarker criteria for acute myocardial infarction; the North Sea Race Endurance
      Exercise Study (NEEDED) 2013.
AB  - BACKGROUND: The aim of this study was to investigate troponin (cTn) dynamics for
      both genders, compared the different release patterns to the gender specific 99th
      percentile and to current biomarker criteria for diagnosing myocardial infarction
      (MI). METHODS: Serum was collected from 97 recreational cyclists 24 h before and
      immediately, 3 and 24 h following a 91-km bike race. hs-cTnI (Abbott) and hs-cTnT
      (Roche) were measured. Conventional or CT coronary angiography was performed in
      the 13 participants with the highest hs-cTnI (>140 ng/L). Three subjects with
      obstructive coronary artery disease were excluded from the statistical analysis.
      RESULTS: There was a significant (p < 0.001) post-race increase in cTnI and cTnT;
      cTnT peaked immediately, cTnI peaked after 3 h. Relative to the gender specific
      99th percentile values, women had the largest increase. The biomarker criteria
      for MI were met in 76-87% for hs-cTnI, and 96-95% for hs-cTnT (p value <0.05),
      within the first 3 h post-race. CONCLUSION: Post-race cardiac troponin
      concentrations exceeded diagnostic criteria for MI in the majority of subjects,
      more often for hs-cTnT than for hs-cTnI, and more pronounced in women than in
      men. The current biomarker criteria for MI discriminate poorly between an
      exercise induced troponin increase and acute MI.

PMID- 29366836
TI  - Prognostic value of microRNA-155 in human carcinomas: An updated meta-analysis.
AB  - BACKGROUND: miR-155 functions as an oncomiR or as an oncosuppressor-miR in human
      cancer. Although miR-155 has been researched in many cancers, its prognostic
      value is uncertain. METHODS: We performed a literature search in up-to-date
      electronic databases including PubMed and Embase to obtain as many relevant
      articles as possible. Combined hazard ratios (HR) of miR-155 for outcome were
      analyzed. RESULTS: A total of 24 papers researching different cancers were
      included in this meta-analysis. Combined HRs showed that miR-155 was
      significantly associated with a poorer OS with HR = 1.99 (1.34-2.96) (I-squared =
      83.1%, P = 0.000). Combined HR of PFS/RFS/DFS was 1.95 (1.14-3.33) (I-squared =
      75.9%, P = 0.000) and CSS/DSS was 2.50 (0.73-8.58) (I-squared = 87.7%, P =
      0.000). CONCLUSION: Increased miR-155 expression was associated with poorer
      survival in human carcinoma and as such may be valuable in predicting outcome.

PMID- 29366835
TI  - Performance of high-sensitivity cardiac troponin in the emergency department for
      myocardial infarction and a composite cardiac outcome across different estimated
      glomerular filtration rates.
AB  - BACKGROUND: Clinicians regularly observe increased high-sensitivity cardiac
      troponin (hs-cTn) concentrations in patients with low estimated glomerular
      filtration rate (eGFR). The challenge is to differentiate acute coronary syndrome
      (ACS) from increased hs-cTn results across a range of eGFR. The objective of this
      study was to determined the optimal hs-cTn concentrations for acute myocardial
      infarction (MI) and a composite cardiovascular outcome across different eGFR
      ranges and to assess the utility of a low hs-cTn cutoff to rule-out events.
      METHODS: We undertook an observational study in the emergency department of
      patients (n = 1212) with symptoms suggestive of ACS who had an eGFR and at least
      one Roche hs-cTnT and one Abbott hs-cTnI result. The 7-day outcomes were MI or a
      composite of MI, unstable angina, congestive heart failure, serious ventricular
      cardiac arrhythmia, or death. The maximum hs-cTn concentration was assessed
      across different eGFR ranges (<30,30-59,60-89,>=90 ml/min/1.73m2) by spearman
      correlation, ROC-curve analyses, and sensitivity and negative predictive value
      (NPV) for the proposed rule-out hs-cTn cutoffs (hs-cTnI<5 ng/l and hs-cTnT<6
      ng/l) for the outcomes. RESULTS: Both hs-cTnI and hs-cTnT concentrations were
      negatively correlated with eGFR. The lower the eGFR, the lower the AUC and the
      higher the optimal hs-cTn cutoffs for both MI and the composite outcome. The
      highest combined sensitivity (100%), NPV (100%) and proportion of low-risk for MI
      (45% of group) was observed for patients with hs-cTnT<6 ng/l with an eGFR>=90.
      CONCLUSION: The test performance for hs-cTn for diagnosing or ruling-out an acute
      cardiac event varies per the eGFR. Accurate risk stratification requires
      knowledge of the eGFR.

PMID- 29366837
TI  - The P2X7 purinergic receptor: An emerging therapeutic target in cardiovascular
      diseases.
AB  - The P2X7 purinergic receptor, a calcium permeable cationic channel, is activated
      by extracellular ATP. Most studies show that P2X7 receptor plays an important
      role in the nervous system diseases, immune response, osteoporosis and cancer.
      Mounting evidence indicates that P2X7 receptor is also associated with
      cardiovascular disease. For example, the P2X7 receptor activated by ATP can
      attenuate myocardial ischemia-reperfusion injury. By contrast, inhibition of P2X7
      receptor decreases arrhythmia after myocardial infarction, prolongs cardiac
      survival after a long term heart transplant, alleviates the dilated
      cardiomyopathy and the autoimmune myocarditis process. The P2X7 receptor also
      mitigates vascular diseases including atherosclerosis, hypertension, thrombosis
      and diabetic retinopathy. This review focuses on the latest research on the role
      and therapeutic potential of P2X7 receptor in cardiovascular diseases.

PMID- 29366838
TI  - Development of a 3D bone marrow adipose tissue model.
AB  - Over the past twenty years, evidence has accumulated that biochemically and
      spatially defined networks of extracellular matrix, cellular components, and
      interactions dictate cellular differentiation, proliferation, and function in a
      variety of tissue and diseases. Modeling in vivo systems in vitro has been
      undeniably necessary, but when simplified 2D conditions rather than 3D in vitro
      models are used, the reliability and usefulness of the data derived from these
      models decreases. Thus, there is a pressing need to develop and validate reliable
      in vitro models to reproduce specific tissue-like structures and mimic functions
      and responses of cells in a more realistic manner for both drug screening/disease
      modeling and tissue regeneration applications. In adipose biology and cancer
      research, these models serve as physiologically relevant 3D platforms to bridge
      the divide between 2D cultures and in vivo models, bringing about more reliable
      and translationally useful data to accelerate benchtop to bedside research.
      Currently, no model has been developed for bone marrow adipose tissue (BMAT), a
      novel adipose depot that has previously been overlooked as "filler tissue" but
      has more recently been recognized as endocrine-signaling and systemically
      relevant. Herein we describe the development of the first 3D, BMAT model derived
      from either human or mouse bone marrow (BM) mesenchymal stromal cells (MSCs). We
      found that BMAT models can be stably cultured for at least 3 months in vitro, and
      that myeloma cells (5TGM1, OPM2 and MM1S cells) can be cultured on these for at
      least 2 weeks. Upon tumor cell co-culture, delipidation occurred in BMAT
      adipocytes, suggesting a bidirectional relationship between these two important
      cell types in the malignant BM niche. Overall, our studies suggest that 3D BMAT
      represents a "healthier," more realistic tissue model that may be useful for
      elucidating the effects of MAT on tumor cells, and tumor cells on MAT, to
      identify novel therapeutic targets. In addition, proteomic characterization as
      well as microarray data (expression of >22,000 genes) coupled with KEGG pathway
      analysis and gene set expression analysis (GSEA) supported our development of
      less-inflammatory 3D BMAT compared to 2D culture. In sum, we developed the first
      3D, tissue-engineered bone marrow adipose tissue model, which is a versatile,
      novel model that can be used to study numerous diseases and biological processes
      involved with the bone marrow.

PMID- 29366839
TI  - Characterization of the bone marrow adipocyte niche with three-dimensional
      electron microscopy.
AB  - Unlike white and brown adipose tissues, the bone marrow adipocyte (BMA) exists in
      a microenvironment containing unique populations of hematopoietic and skeletal
      cells. To study this microenvironment at the sub-cellular level, we performed a
      three-dimensional analysis of the ultrastructure of the BMA niche with focused
      ion beam scanning electron microscopy (FIB-SEM). This revealed that BMAs display
      hallmarks of metabolically active cells including polarized lipid deposits, a
      dense mitochondrial network, and areas of endoplasmic reticulum. The distinct
      orientations of the triacylglycerol droplets suggest that fatty acids are taken
      up and/or released in three key areas - at the endothelial interface, into the
      hematopoietic milieu, and at the bone surface. Near the sinusoidal vasculature,
      endothelial cells send finger-like projections into the surface of the BMA which
      terminate near regions of lipid within the BMA cytoplasm. In some regions,
      perivascular cells encase the BMA with their flattened cellular projections,
      limiting contacts with other cells in the niche. In the hematopoietic milieu,
      BMAT adipocytes of the proximal tibia interact extensively with maturing cells of
      the myeloid/granulocyte lineage. Associations with erythroblast islands are also
      prominent. At the bone surface, the BMA extends organelle and lipid-rich
      cytoplasmic regions toward areas of active osteoblasts. This suggests that the
      BMA may serve to partition nutrient utilization between diverse cellular
      compartments, serving as an energy-rich hub of the stromal-reticular network.
      Lastly, though immuno-EM, we've identified a subset of bone marrow adipocytes
      that are innervated by the sympathetic nervous system, providing an additional
      mechanism for regulation of the BMA. In summary, this work reveals that the bone
      marrow adipocyte is a dynamic cell with substantial capacity for interactions
      with the diverse components of its surrounding microenvironment. These local
      interactions likely contribute to its unique regulation relative to peripheral
      adipose tissues.

PMID- 29366840
TI  - Lamin A/C Maintains Exocrine Pancreas Homeostasis by Regulating Stability of RB
      and Activity of E2F.
AB  - Lamins have important roles in nuclear structure and cell signaling. Several
      diseases are associated with mutations in the lamin A/C gene (LMNA in humans).
      Patients with familial partial lipodystrophy caused by LMNA mutations develop
      pancreatitis, but lamin function in the pancreas and how these mutations affect
      pancreatic regulation are unknown. We generated mice with inducible exocrine
      pancreas-specific disruption of Lmna and showed that LMNA is lost from most
      exocrine pancreas cells. LMNA-knockout pancreata develop endoplasmic reticulum
      stress with loss of acinar cell markers, increased autophagy, apoptosis, and cell
      proliferation, compared to CreERT2- mice (littermate controls). Disruption of
      Lmna led to a phenotype that resembled chronic pancreatitis, with increased
      Sirius Red staining and alpha-smooth muscle actin in male LMNA-knockout mice
      compared to littermate males, but not in female mice. LMNA-knockout pancreata
      have reduced levels of RB and activation of E2F, based on increased expression of
      E2F target genes. Therefore, lamins maintain pancreatic homeostasis by regulating
      RB stability and E2F activity.

PMID- 29366841
TI  - Bi-directionality of Brain-Gut Interactions in Patients With Inflammatory Bowel
      Disease.
AB  - BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are associated with mood
      disorders, such as anxiety or depression, but it is not clear whether one
      contributes to development of the other, or if the interaction is bi-directional
      (anxiety or depression contributes to the progression of IBD, and IBD affects
      psychological health). We performed a 2-year longitudinal prospective study of
      patients in secondary to care investigate the bi-directionality of IBD and mood
      disorders. METHODS: We collected data from 405 adult patients with a diagnosis of
      Crohn's disease (CD) or ulcerative colitis (UC) from November 2012 through June
      2017. Demographic features, subtypes of IBD, treatments, symptoms, somatization,
      and fecal level of calprotectin were recorded at baseline. IBD activity was
      determined at baseline and after the follow-up period (2 years or more) using the
      Harvey-Bradshaw Index for CD and the Simple Clinical Colitis Activity Index for
      UC (scores >=5 used to define disease activity). Anxiety and depression data were
      collected using the Hospital Anxiety and Depression Scale (HADS), at baseline and
      after the follow-up period. Objective markers of disease activity, including
      glucocorticosteroid prescription or flare of disease activity, escalation of
      therapy, hospitalization secondary to IBD activity, and intestinal resection
      during follow-up were assessed via case note review. A brain-gut direction of
      disease activity was defined as development of new IBD activity in patients with
      quiescent IBD and abnormal HADS scores at baseline. A gut-brain direction of
      disease activity was defined by subsequent development of abnormal HADS scores in
      patients with active IBD and normal HADS scores at baseline. We performed
      multivariate Cox regression controlling for patient characteristics and follow-up
      duration. RESULTS: Baseline CD or UC disease activity were associated with an
      almost 6-fold increase in risk for a later abnormal anxiety score (hazard ratio
      [HR], 5.77; 95% CI, 1.89-17.7). In patients with quiescent IBD at baseline,
      baseline abnormal anxiety scores were associated with later need for
      glucocorticosteroid prescription or flare of IBD activity (HR, 2.08; 95% CI, 1.31
      3.30) and escalation of therapy (HR, 1.82; 95% CI, 1.19-2.80). These associations
      persisted when normal IBD activity index scores and fecal level of calprotectin
      <250 MUg/g were used to define quiescent disease at baseline. CONCLUSIONS: In a 2
      year study of patients with CD or UC, we found evidence for bi-directional
      effects of IBD activity and psychological disorders. Patients with IBD should be
      monitored for psychological well-being.

PMID- 29366842
TI  - Histologic Factors Associated With Need for Surgery in Patients With Pedunculated
      T1 Colorectal Carcinomas.
AB  - BACKGROUND & AIMS: Most patients with pedunculated T1 colorectal tumors referred
      for surgery are not found to have lymph node metastases, and were therefore
      unnecessarily placed at risk for surgery-associated complications. We aimed to
      identify histologic factors associated with need for surgery in patients with
      pedunculated T1 colorectal tumors. METHODS: We performed a cohort-nested matched
      case-control study of 708 patients diagnosed with pedunculated T1 colorectal
      tumors at 13 hospitals in The Netherlands, from January 1, 2000 through December
      31, 2014, followed for a median of 44 months (interquartile range, 20-80 months).
      We identified 37 patients (5.2%) who required surgery (due to lymph node,
      intramural, or distant metastases). These patients were matched with patients
      with pedunculated T1 colorectal tumors without a need for surgery (no metastases,
      controls, n = 111). Blinded pathologists analyzed specimens from each tumor,
      stained with H&E. We evaluated associations between histologic factors and
      patient need for surgery using univariable conditional logistic regression
      analysis. We used multivariable least absolute shrinkage and selection operator
      (LASSO; an online version of the LASSO model is available at:
      http://t1crc.com/calculator/) regression to develop models for identification of
      patients with tumors requiring surgery, and tested the accuracy of our model by
      projecting our case-control data toward the entire cohort (708 patients). We
      compared our model with previously developed strategies to identify high-risk
      tumors: conventional model 1 (based on poor differentiation, lymphovascular
      invasion, or Haggitt level 4) and conventional model 2 (based on poor
      differentiation, lymphovascular invasion, Haggitt level 4, or tumor budding).
      RESULTS: We identified 5 histologic factors that differentiated cases from
      controls: lymphovascular invasion, Haggitt level 4 invasion, muscularis mucosae
      type B (incompletely or completely disrupted), poorly differentiated clusters and
      tumor budding, which identified patients who required surgery with an area under
      the curve (AUC) value of 0.83 (95% confidence interval, 0.76-0.90). When we used
      a clinically plausible predicted probability threshold of >=4.0%, 67.5% (478 of
      708) of patients were predicted to not need surgery. This threshold identified
      patients who required surgery with 83.8% sensitivity (95% confidence interval,
      68.0%-93.8%) and 70.3% specificity (95% confidence interval, 60.9%-78.6%).
      Conventional models 1 and 2 identified patients who required surgery with lower
      AUC values (AUC, 0.67; 95% CI, 0.60-0.74; P = .002 and AUC, 0.64; 95% CI, 0.58
      0.70; P < .001, respectively) than our LASSO model. When we applied our LASSO
      model with a predicted probability threshold of >=4.0%, the percentage of missed
      cases (tumors mistakenly assigned as low risk) was comparable (6 of 478 [1.3%])
      to that of conventional model 1 (4 of 307 [1.3%]) and conventional model 2 (3 of
      244 [1.2%]). However, the percentage of patients referred for surgery based on
      our LASSO model was much lower (32.5%, n = 230) than that for conventional model
      1 (56.6%, n = 401) or conventional model 2 (65.5%, n = 464). CONCLUSIONS: In a
      cohort-nested matched case-control study of 708 patients with pedunculated T1
      colorectal carcinomas, we developed a model based on histologic features of
      tumors that identifies patients who require surgery (due to high risk of
      metastasis) with greater accuracy than previous models. Our model might be used
      to identify patients most likely to benefit from adjuvant surgery.

PMID- 29366843
TI  - Combined iron chelator and T-type calcium channel blocker exerts greater efficacy
      on cardioprotection than monotherapy in iron-overload thalassemic mice.
AB  - Although both iron chelators and T-type calcium channel (TTCC) blockers have been
      shown to exert cardioprotection by decreasing cardiac iron deposition and
      reducing left ventricular (LV) dysfunction via different channels in iron
      overloaded rodent models, the cardioprotective effects of combined iron chelator
      and TTCC blocker treatment in thalassemic mice has not been investigated. We
      hypothesized that a combined iron chelator and TTCC blocker exerts better
      cardioprotection than monotherapy by decreasing cardiac iron accumulation,
      apoptosis and oxidative stress. An iron-overload condition was induced in
      heterozygous betaKO thalassemic (HT) mice and wild-type (WT) mice by high iron
      diet consumption (FE) for 3 months. Then, the iron chelator deferiprone (DFP),
      the TTCC blocker efonidipine (Efo), and combined DFP plus Efo were fed via oral
      gavage for 1 month whilst the high iron diet was continued. LV function, heart
      rate variability (HRV), apoptosis and cardiac iron accumulation were determined.
      Chronic iron-overload in mice led to increased cardiac iron deposition, oxidative
      stress, apoptosis, and impaired LV function and HRV. Although DFP and Efo showed
      similar cardioprotective efficacy, the combined DFP plus Efo therapy exerted
      greater efficacy in reducing cardiac iron deposition and cellular apoptosis than
      either of the monotherapies in iron-overload thalassemic mice.

PMID- 29366844
TI  - Multigene Signature Panels and Breast Cancer Therapy: Patterns of Use and Impact
      on Clinical Decision Making.
AB  - BACKGROUND: A growing body of evidence supports the use of multigene signature
      panels (MSPs) in predicting recurrence risk in patients with invasive breast
      cancer. This study aimed to evaluate trends in MSP use over time and the effect
      of MSPs on administration of postoperative chemotherapy. STUDY DESIGN: The
      National Cancer Database was queried for all women with invasive breast cancer
      who underwent resection between 2011 and 2014 and had information about
      performance of an MSP, hormone receptor status, and receipt of chemotherapy.
      Multigene signature panel use over time was evaluated, and patterns of use of
      Oncotype DX (ODX) and MammaPrint (MP) were compared. RESULTS: In a total of
      476,128 patients, an MSP was obtained in 153,782 (30.2%). Multigene signature
      panel use increased over time and was associated with a decreased rate of
      chemotherapy administration (24.6% MSP vs 37.2% no MSP; p < 0.001). Oncotype DX
      remained the most common MSP used throughout the study period. Oncotype DX was
      used more commonly in stage I disease than MP, and MP was used more commonly in
      stage II and III disease. MammaPrint was more commonly used in hormone receptor
      negative patients, human epidermal growth factor receptor 2-positive patients,
      and patients with positive lymph nodes. Postoperative chemotherapy was
      administered to a higher proportion of patients assessed with MP than with ODX
      (41.3% vs 23.4%, respectively; p < 0.001). CONCLUSIONS: Use of MSPs among
      patients with breast cancer has increased over time and is associated with a
      decreased use of adjuvant chemotherapy. Oncotype DX continues to be the most
      widely used MSP, although MP use has increased over time. Future studies are
      warranted to determine the optimal use of these MSPs in risk assessment and
      postoperative decision making.

PMID- 29366845
TI  - The incidence, psychiatric co-morbidity and pharmacological treatment of severe
      mental disorders in children and adolescents.
AB  - BACKGROUND: Antipsychotic drug use among children and adolescents is increasing,
      and there is growing concern about off-label use and adverse effects. The present
      study aims to investigate the incidence, psychiatric co-morbidity and
      pharmacological treatment of severe mental disorder in Norwegian children and
      adolescents. METHODS: We obtained data on mental disorders from the Norwegian
      Patient Registry on 0-18 year olds who during 2009-2011 were diagnosed for the
      first time with schizophrenia-like disorder (International Classification of
      Diseases, 10th revision codes F20-F29), bipolar disorder (F30-F31), or severe
      depressive episode with psychotic symptoms (F32.3 or F33.3). Data on filled
      prescriptions for psychotropic drugs were obtained from the Norwegian
      Prescription Database. RESULTS: A total of 884 children and adolescents (25.1 per
      100 000 person years) were first time diagnosed with schizophrenia-like disorder
      (12.6 per 100 000 person years), bipolar disorder (9.2 per 100 000 person years),
      or severe depressive episode with psychotic symptoms (3.3 per 100 000 person
      years) during 2009-2011. The most common co-morbid mental disorders were
      depressive (38.1%) and anxiety disorders (31.2%). Antipsychotic drugs were
      prescribed to 62.4% of the patients, 72.0% of the schizophrenia-like disorder
      patients, 51.7% of the bipolar disorder patients, and 55.4% of the patients with
      psychotic depression. The most commonly prescribed drugs were quetiapine (29.5%),
      aripiprazole (19.6%), olanzapine (17.3%), and risperidone (16.6%). CONCLUSIONS:
      When a severe mental disorder was diagnosed in children and adolescents, the
      patient was usually also prescribed antipsychotic medication. Clinicians must be
      aware of the high prevalence of depressive and anxiety disorders among early
      psychosis patients.

PMID- 29366846
TI  - Affectively salient signal to random noise might be used to identify psychosis
      vulnerability in severe mental disorders.
AB  - BACKGROUND: Subclinical psychotic symptoms are present in the general population.
      Furthermore, they are quite common in diagnostic categories beyond psychosis,
      such as BPD patients. METHODS: We want to assess the differences between 3
      groups: BPD (n = 68), FEP (n = 83) and controls (n = 203) in an experimental
      paradigm measuring the presence of speech illusions in white noise. The Positive
      and Negative Syndrome Scale was administered in the patient group, the Structured
      Interview for Schizotypy-Revised, and the Community Assessment of Psychic
      Experiences in the control and BPD group. The white noise task was also analysed
      within a signal detection theory (SDT) framework. Logistic regression analyses
      and the general linear models were used to analyse the adjusted differences
      between groups. RESULTS: Differences were more prevalent in signals that were
      perceived as affectively salient in patients groups (9.6% in FEP vs 5.9% in BPD
      and 1% in controls; OR: 10.7; 95%CI: 2.2-51.6, p = 0.003 in FEP; OR: 6.3; 95%CI:
      1.1-35.0, p = 0.036 in BPD). Besides, we found a worse general performance and
      more false alarms in the task for FEP group using SDT framework. CONCLUSIONS:
      Experimental paradigms indexing the tendency to detect affectively salient
      signals in noise may be used to identify liability to psychosis in people with
      vulnerability. Its predictable value in other diagnostic categories and general
      population requires further research.

PMID- 29366847
TI  - Emotion regulation as a moderator of the interplay between self-reported and
      physiological stress and paranoia.
AB  - Experience sampling method (ESM) studies have found an association between daily
      stress and paranoid symptoms, but it is uncertain whether these findings
      generalize to physiological indicators of stress. Moreover, the temporality of
      the association and its moderating factors require further research. Here, we
      investigate whether physiological and self-rated daily stress predict subsequent
      paranoid symptoms and analyze the role of emotion regulation as a putative
      moderator. We applied ESM during 24 h to repeatedly assess heart rate, self-rated
      stress, and subclinical paranoia in a sample of 67 psychosis-prone individuals as
      measured with Community Assessment for Psychotic Experiences (CAPE). Adaptive and
      maladaptive emotion regulation was assessed at baseline with the Emotion
      Regulation Skills Questionnaire (ERSQ-ES) and the Cognitive Emotion Regulation
      Questionnaire (CERQ). Linear mixed models were used to analyze the data. Heart
      rate (b = 0.004, p < 0.05) and self-rated stress (b = 0.238, p < 0.001) predicted
      subsequent paranoia. The reverse effect, paranoia as a predictor of subsequent
      heart rate (b = 0.230, p = 0.615) or self-rated stress (b = -0.009, p = 0.751)
      was non-significant. Maladaptive emotion regulation was a significant predictor
      of paranoia (b = 0.740, p < 0.01) and moderated the path from self-rated stress
      to paranoia (b = 0.188, p < 0.05) but not the path from heart rate to paranoia (b
      = 0.005, p = 0.09). Our findings suggest a one-way temporal link between daily
      stress and paranoia and highlight the importance of emotion regulation as a
      vulnerability factor relevant to this process.

PMID- 29366848
TI  - Amendment of traditional assessment measures for the negative symptoms of
      schizophrenia.
AB  - : Schizophrenia research based on traditional assessment measures for negative
      symptoms appears to be, to some extent, unreliable. The limitations of the
      Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of
      Negative Symptoms (SANS) have been extensively acknowledged and should be taken
      into account. The aim of this study is to show how the PANSS and the SANS
      conflate negative symptoms and cognition and to offer alternatives for the
      limitations found. METHODS: A sample of 117 participants with schizophrenia from
      two independent studies was retrospectively investigated. Linear regression
      models were computed to explore the effect of negative symptoms and illness
      duration as predictors of cognitive performance. RESULTS: For the PANSS, the item
      "abstract thinking" accounted for the association between negative symptoms and
      cognition. For the SANS, the "attention" subscale predicted the performance in
      verbal memory, but illness duration emerged as a stronger predictor than negative
      symptoms for outcomes of processing speed, verbal and working memory. CONCLUSION:
      Utilizing alternative models to the traditional PANSS and SANS formats, and
      accounting for illness duration, provide more precise evidence on the
      relationship between negative symptoms and cognition. Since these measures are
      still extensively utilized, we recommend adopting more rigorous approaches to
      avoid misleading results.

PMID- 29366849
TI  - Disability and common mental disorders: Results from the World Mental Health
      Survey Initiative Portugal.
AB  - BACKGROUND: Common mental disorders are highly prevalent and disabling, leading
      to substantial individual and societal costs. This study aims to characterize the
      association between disability and common mental disorders in Portugal, using
      epidemiological data from the World Mental Health Survey Initiative. METHODS:
      Twelve-month common mental disorders were assessed with the CIDI 3.0. Disability
      was evaluated with the modified WMHS WHODAS-II. Logistic regression models were
      used to assess the association between disability and each disorder or diagnostic
      category (mood or anxiety disorders). RESULTS: Among people with a common mental
      disorder, 14.6% reported disability. The specific diagnoses significantly
      associated with disability were post-traumatic stress disorder (OR: 6.69; 95% CI:
      3.20, 14.01), major depressive disorder (OR: 3.49; 95% CI: 2.13, 5.72), bipolar
      disorder (OR: 3.41; 95% CI: 1.04, 11.12) and generalized anxiety disorder (OR:
      3.14; 95% CI: 1.43, 6.90). Both categories of anxiety and mood disorders were
      significantly associated with disability (OR: 1.88; 95% CI: 1.23, 2.86 and OR:
      3.94; 95% CI: 2.45, 6.34 respectively). CONCLUSIONS: The results of this study
      add to the current knowledge in this area by assessing the disability associated
      with common mental disorders using a multi-dimensional instrument, which may
      contribute to mental health policy efforts in the development of interventions to
      reduce the burden of disability associated with common mental disorders.

PMID- 29366850
TI  - The Fat-Dachsous signaling pathway regulates growth of horns in Trypoxylus
      dichotomus, but does not affect horn allometry.
AB  - Males of the Asian rhinoceros beetle, Trypoxylus dichotomus, possess exaggerated
      head and thoracic horns that scale dramatically out of proportion to body size.
      While studies of insulin signaling suggest that this pathway regulates nutrition
      dependent growth including exaggerated horns, what regulates disproportionate
      growth has yet to be identified. The Fat signaling pathway is a potential
      candidate for regulating disproportionate growth of sexually-selected traits, a
      hypothesis we advanced in a previous paper (Gotoh et al., 2015). To investigate
      the role of Fat signaling in the growth and scaling of the sexually dimorphic,
      condition-dependent traits of the in the Asian rhinoceros beetle T. dichotomus,
      we used RNA interference to knock down expression of fat and its co-receptor
      dachsous. Knockdown of fat, and to a lesser degree dachsous, caused shortening
      and widening of appendages, including the head and thoracic horns. However,
      scaling of horns to body size was not affected. Our results show that Fat
      signaling regulates horn growth in T. dichotomus as it does in appendage growth
      in other insects. However, we provide evidence that Fat signaling does not
      mediate the disproportionate, positive allometric growth of horns in T.
      dichotomus.

PMID- 29366851
TI  - Cadopherone and colomitide polyketides from Cadophora wood-rot fungi associated
      with historic expedition huts in Antarctica.
AB  - Recent investigations of filamentous fungi isolated from coastal areas and
      historic wooden structures in the Ross Sea and Peninsula regions of Antarctica
      have identified the genus Cadophora as one of the most abundant fungal groups,
      comprising more than 30% of culturable fungi at some locations. A methanol
      extract of Cadophora luteo-olivacea grown on rice media yielded the known
      polyketides spiciferone A, spiciferol A, dihydrospiciferone A and
      dihydrospiciferol A. Additionally, nine related hexaketides were identified,
      including spiciferone F, two isomers of the known fungal bicyclic ketal
      colomitide B, cadopherones A-D, similin C, and spicifernin B. HPLC and NMR
      analysis of extracts from other isolates collected in Antarctica suggests that
      the spiciferones and colomitides are produced by at least two different Cadophora
      species. Preliminary precursor feeding experiments provided evidence for the
      biosynthesis of the colomitides from the same polyketide pathway as the
      spiciferone phytotoxins, possibly via a type III polyketide synthase (PKS). None
      of the compounds were active in a panel of anti-bacterial, anti-fungal, and
      mammalian cytotoxicity assays.

PMID- 29366852
TI  - Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural
      antimicrobial agents.
AB  - A fungal strain, Drechmeria sp., was isolated from the root of Panax notoginseng.
      Totally, seven new indole diterpenoids, drechmerins A-G (1-7), were isolated from
      the fermentation broth of Drechmeria sp. together with four known analogues (8
      11). Their structures were determined on the basis of 1D and 2D NMR and
      electronic circular dichroism (ECD) spectroscopic analyses as well as theoretical
      calculations. All the isolated compounds were evaluated for their antimicrobial
      activities against Candida albicans, Staphylococcus aureus, Bacillus cereus, B.
      subtillis, Pseudomonas aeruginosa, and Klebsiella pneumonia, respectively.
      Drechmerin B (2) displayed antimicrobial activity against C. albicans with an MIC
      value of 12.5 MUg/mL. Molecular docking was used to investigate interactions of
      peptide deformylase with compounds 1-3, 5-7, 9, and 10.

PMID- 29366854
TI  - Grading of Urothelial Carcinoma and The New "World Health Organisation
      Classification of Tumours of the Urinary System and Male Genital Organs 2016".
AB  - CONTEXT: In the management of urothelial carcinoma, determination of the
      pathological grade aims at stratifying tumours into different prognostic groups
      to allow evaluation of treatment results, and optimise patient management. This
      article reviews the principles behind different grading systems for urothelial
      bladder carcinoma discussing their reproducibility and prognostic value.
      OBJECTIVE: This paper aims to show the evolution of the World Health Organisation
      (WHO) grading system, discussing their reproducibility and prognostic value, and
      evaluating which classification system best predicts disease recurrence and
      progression. The most optimal classification system is robust, reproducible, and
      transparent with comprehensive data on interobserver and intraobserver
      variability. The WHO published an updated tumour classification in 2016, which
      presents a step forward, but its performance will need validation in clinical
      studies. EVIDENCE ACQUISITION: Medline and EMBASE were searched using the key
      terms WHO 1973, WHO/International Society of Urological Pathology 1998, WHO 2004,
      WHO 2016, histology, reproducibility, and prognostic value, in the time frame
      1973 to May 2016. The references list of relevant papers was also consulted,
      resulting in the selection of 48 papers. EVIDENCE SYNTHESIS: There are still
      inherent limitations in all available tumour classification systems. The WHO 1973
      presents considerable ambiguity for classification of the G2 tumour group and
      grading of the G1/2 and G2/3 groups. The 2004 WHO classification introduced the
      concept of low-grade and high-grade tumours, as well as the papillary urothelial
      neoplasm of low malignant potential category which is retained in the 2016
      classification. Furthermore, while molecular markers are available that have been
      shown to contribute to a more accurate histological grading of urothelial
      carcinomas, thereby improving selection of treatment for a given patient, these
      are not (yet) part of standard clinical practice. CONCLUSIONS: The prognosis of
      patients diagnosed with urothelial carcinoma greatly depends on correct
      histological grading of the tumour. There is still limited data regarding
      intraobserver and interobserver variability differences between the WHO 1973 and
      2004 classification systems. Additionally, reproducibility remains a concern:
      histological differences between the various types of tumour may be subtle and
      there is still no consensus amongst pathologists. The recent WHO 2016
      classification presents a further improvement on the 2004 classification, but
      until further data becomes available, the European Association of Urology
      currently recommends the use of both WHO 1973 and WHO 2004/2016 classifications.
      PATIENT SUMMARY: Bladder cancer, when treated in time, has a good prognosis.
      However, selection of the most optimal treatment is largely dependent on the
      information your doctor will receive from the pathologist following evaluation of
      the tissue resected from the bladder. It is therefore important that the
      classification system that the pathologist uses to grade the tissue is
      transparent and clear for both urologists and pathologists. A reliable
      classification system will ensure that aggressive tumours are not misinterpreted,
      and less aggressive cancer is not overtreated.

PMID- 29366853
TI  - Lipidomic analysis of Botryococcus (Trebouxiophyceae, Chlorophyta) -
      Identification of lipid classes containing very long chain fatty acids by offline
      two-dimensional LC-tandem MS.
AB  - Very long chain fatty acids (VLCFAs) were identified in four strains of the green
      alga Botryococcus braunii (Trebouxiophyceae). The algae contained a series of
      monoenoic fatty acids up to triacontenoic acid and further VLCFAs in amounts
      around 1% of total fatty acids. The separation of lipid classes using hydrophilic
      interaction chromatography revealed that the most abundant VLCFAs (28:2, 28:1 and
      28:0) were contained in neutral lipids (triacylglycerols and/or diacylglycerols)
      and in phospholipids (phosphatidic acid and/or phosphatidylcholine). Using non
      aqueous reversed-phase liquid chromatography tandem mass spectrometry (NARP
      LC/MS2) of the appropriate collected fractions, molecular species of
      triacylglycerols containing one or two VLCFAs were described and
      phosphatidylcholines containing VLCFAs were separated for the first time. Because
      the presence of Botryosphaerella sudetica (Chlorophyceae) as contaminant of
      Botryococcus braunii strain Droop 1950/807-1 placed some doubts on the results of
      previous studies, a strain of this green alga of was also analyzed. In contrast
      to Botryococcus, C16, a substantially lower proportion of C18 polyunsaturated
      fatty acids and no VLCFAs were detected in Botryosphaerella.

PMID- 29366855
TI  - Quality of Life After Open Radical Prostatectomy Compared with Robot-assisted
      Radical Prostatectomy.
AB  - BACKGROUND: Surgery for prostate cancer has a large impact on quality of life
      (QoL). OBJECTIVE: To evaluate predictors for the level of self-assessed QoL at 3
      mo, 12 mo, and 24 mo after robot-assisted laparoscopic (RALP) and open radical
      prostatectomy (ORP). DESIGN, SETTING, AND PARTICIPANTS: The LAParoscopic
      Prostatectomy Robot Open study, a prospective, controlled, nonrandomised trial of
      more than 4000 men who underwent radical prostatectomy at 14 centres. Here we
      report on QoL issues after RALP and ORP. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: The primary outcome was self-assessed QoL preoperatively and at 3 mo,
      12 mo, and 24 mo postoperatively. A direct validated question of self-assessed
      QoL on a seven-digit visual scale was used. Differences in QoL were analysed
      using logistic regression, with adjustment for confounders. RESULTS AND
      LIMITATIONS: QoL did not differ between RALP and ORP postoperatively. Men
      undergoing ORP had a preoperatively significantly lower level of self-assessed
      QoL in a multivariable analysis compared with men undergoing RALP (odds ratio:
      1.21, 95% confidence interval: 1.02-1.43), that disappeared when adjusted for
      preoperative preparedness for incontinence, erectile dysfunction, and certainty
      of being cured (odds ratio: 1.18, 95% confidence interval: 0.99-1.40).
      Incontinence and erectile dysfunction increased the risk for poor QoL at 3 mo, 12
      mo, and 24 mo postoperatively. Biochemical recurrence did not affect QoL. A
      limitation of the study is the nonrandomised design. CONCLUSIONS: QoL at 3 mo, 12
      mo, and 24 mo after RALP or ORP did not differ significantly between the two
      techniques. Poor QoL was associated with postoperative incontinence and erectile
      dysfunction but not with early cancer relapse, which was related to thoughts of
      death and waking up at night with worry. PATIENT SUMMARY: We did not find any
      difference in quality of life at 3 mo, 12 mo, and 24 mo when open and robot
      assisted surgery for prostate cancer were compared. Postoperative incontinence
      and erectile dysfunction were associated with poor quality of life.

PMID- 29366856
TI  - Contemporary Trends and Survival Outcomes After Aborted Radical Prostatectomy in
      Lymph Node Metastatic Prostate Cancer Patients.
AB  - BACKGROUND: Aborted radical prostatectomy (aRP) in lymph node (LN) metastatic
      (pN1) prostate cancer (PCa) patients showed worse survival in European patients.
      Contemporary rates of aRP are unknown in North America. OBJECTIVE: To examine the
      rate of aRP and its effect on cancer-specific mortality (CSM) in contemporary
      North American patients. DESIGN, SETTING, AND PARTICIPANTS: Within the
      Surveillance Epidemiology and End Results database (2004-2014), we identified
      3719 pN1 PCa patients. INTERVENTION: RP. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Incidence proportion and median survival of LN metastatic PCa patients
      who underwent aRP versus completed RP (cRP). Cumulative incidence plots and
      competing-risks regression (CRR) models tested CSM and other-cause mortality
      rates according to aRP versus cRP. The effect of selected variables on CSM rate
      was graphically depicted using LOESS methodology. All analyses were repeated
      after propensity score matching. RESULTS AND LIMITATIONS: Between 2004 and 2014,
      the rate of aRP decreased from 20.4% to 5.6% (p<0.001). Ten-year CSM rates were
      significantly higher after aRP (38.9% vs 21.6%) versus cRP (p<0.001). In
      multivariable CRR models, aRP yielded higher CSM (hazard ratio [HR]: 1.99) than
      cRP. A higher 5-yr CSM rate was recorded after aRP through the entire range of
      baseline prostate-specific antigen (PSA) values and in patients with up to nine
      LN metastases. After propensity score matching, aRP resulted in overall higher
      CSM (HR: 1.72). Higher CSM was recorded after aRP for PSA values up to 50ng/ml
      and in patients with up to seven LN metastases. Results were limited by a
      selection bias that applies to aRP patients. CONCLUSIONS: Of contemporary North
      American patients, 5% are affected by aRP. It confers a significant survival
      disadvantage that applies to patients with baseline PSA values up to 50ng/ml and
      in those with up to seven LN metastases. PATIENT SUMMARY: Radical prostatectomy
      should not be aborted in pN1 prostate cancer individuals.

PMID- 29366857
TI  - A Simplified Frailty Index to Predict Outcomes After Radical Cystectomy.
AB  - BACKGROUND: Traditional surgical risk indices are notoriously inaccurate,
      especially for the elderly, so there has been a trend to evaluate frailty
      instead. OBJECTIVE: To describe a simplified five-item frailty index for
      evaluating radical cystectomy outcomes and compare its predictive ability with
      other risk assessment tools for a total patient cohort and a subgroup of patients
      aged >=65yr. DESIGN, SETTING, AND PARTICIPANTS: The National Surgical Quality
      Improvement Program (NSQIP) database from 2007 to 2015 was queried for radical
      cystectomy cases for bladder cancer. A simplified five-item frailty index (sFI)
      was created based on previously described measures of frailty. OUTCOME
      MEASUREMENT AND STATISTICAL ANALYSIS: Correlation of the sFI with postoperative
      outcomes was investigated using multivariate logistic regression analyses. The
      predictive ability of the sFI was compared to the extended 11-item frailty index,
      NSQIP risk calculator, and the American Society of Anesthesiologists (ASA) score
      by comparing the area under the receiver operating characteristic curve. Subgroup
      analysis was performed for those aged >=65 yr to evaluate the accuracy of the
      index in the older age group, for which traditional risk indices are notoriously
      inaccurate. RESULTS AND LIMITATIONS: Of 5516 cases identified, 10.7% experienced
      a Clavien grade >=3 complication within 30 d of surgery. Individuals with an sFI
      of 3+ had a greater likelihood of experiencing a major complication (odds ratio
      3.22, 95% confidence interval 2.01-5.17). The sFI outperformed the ASA score in
      predicting major complications and had a similar predictive ability to the more
      complex 11-item index and NSQIP risk calculator. There was also a significant
      correlation between the sFI and discharge destination. These relationships were
      consistent in the subgroup of patients aged >=65yr. The study is limited by the
      database, which only records 30-d outcomes and does not allow evaluation of long
      term sequelae. CONCLUSIONS: There is a strong correlation between frailty
      assessed via the sFI and radical cystectomy outcomes, including in the elderly.
      This tool can be used in the clinical setting to counsel patients and aid
      decision-making. PATIENT SUMMARY: This study demonstrated that a simple five-item
      frailty index can be used to assess preoperative risk in patients undergoing
      radical cystectomy.

PMID- 29366858
TI  - Non-O1, non-O139 Vibrio cholerae septicemia at a tertiary care center in Beirut,
      Lebanon; a case report and review.
AB  - More clinical infections with non-O1, non-O139 Vibrio cholerae have been recently
      reported. These pathogens usually do not cause the epidemic and pandemic cases of
      cholera seen with choleragenic vibrios. However, they can still cause intestinal
      as well as extra-intestinal disease and can be associated with significant
      mortality. Herein, we present the first case of non-O1, non-O139 Vibrio cholerae
      septicemia reported in Lebanon since the beginning of the Lebanese waste crisis.

PMID- 29366859
TI  - Endogenous Opiates and Behavior: 2016.
AB  - This paper is the thirty-ninth consecutive installment of the annual review of
      research concerning the endogenous opioid system. It summarizes papers published
      during 2016 that studied the behavioral effects of molecular, pharmacological and
      genetic manipulation of opioid peptides, opioid receptors, opioid agonists and
      opioid antagonists. The particular topics that continue to be covered include the
      molecular-biochemical effects and neurochemical localization studies of
      endogenous opioids and their receptors related to behavior, and the roles of
      these opioid peptides and receptors in pain and analgesia, stress and social
      status, tolerance and dependence, learning and memory, eating and drinking, drug
      abuse and alcohol, sexual activity and hormones, pregnancy, development and
      endocrinology, mental illness and mood, seizures and neurologic disorders,
      electrical-related activity and neurophysiology, general activity and locomotion,
      gastrointestinal, renal and hepatic functions, cardiovascular responses,
      respiration and thermoregulation, and immunological responses.

PMID- 29366860
TI  - Bioinformatic analysis of regulation of natural antisense transcripts by
      transposable elements in human mRNA.
AB  - Non-coding RNA is no longer considered to be "junk" DNA, based on evidence
      uncovered in recent decades. In particular, the important role played by natural
      antisense transcripts (NATs) in regulating the expression of genes is receiving
      increasing attention. However, the regulatory mechanisms of NATs remain
      incompletely understood. It is well-known that the insertion of transposable
      elements (TEs) can affect gene transcription. Using a bioinformatics approach, we
      identified NATs using human mRNA sequences from the UCSC Genome Browser Database.
      Our in silico analysis identified 1079 NATs and 700 sense-antisense gene pairs.
      We identified 179 NATs that showed evidence of having been affected by TEs during
      cellular gene expression. These findings may provide an understanding of the
      complex regulation mechanisms of NATs. If our understanding of NATs as modulators
      of gene expression is further enhanced, we can develop ways to control gene
      expression.

PMID- 29366861
TI  - Functional network analysis reveals biological roles of lncRNAs and mRNAs in
      MOG35-55 specific CD4+T helper cells.
AB  - Long non-coding RNAs have the potential to regulate immune responses. Their
      impact on multiple sclerosis has remained elusive. For illustrating their roles
      in experimental autoimmune encephalomyelitis (EAE) pathogenesis, we investigated
      the differential expression of lncRNAs and mRNAs in CD4+Th cells obtained from
      myelin oligodendrocytic glycoprotein35-55(MOG35-55)-induced EAE and complete
      Freund's adjuvant (CFA) controls. We observed differential expression of 1112
      lncRNAs and 519 mRNAs in CD4+Th cells. The functional network showed lncRNAs had
      the capacity to modulate EAE pathogenesis via regulating many known EAE
      regulators such as Ptpn6. Predicting the function of lncRNAs demonstrated that
      dysregulated lncRNAs were closely associated with the development of EAE. These
      dysregulated lncRNAs may have function in EAE and they could be novel biomarkers
      and therapeutic targets of EAE. However, the precise mechanisms and biological
      functions of these specific lncRNAs in EAE pathogenesis require further study.

PMID- 29366862
TI  - H-NS is an activator of exopolysaccharide biosynthesis genes transcription in
      Vibrio parahaemolyticus.
AB  - Vibrio parahaemolyticus is capable of surviving in biofilm communities attached
      to biotic and abiotic surfaces. The exopolysaccharide (EPS) plays a key role in
      the maturing of the biofilm. The VPA1403-1412 (cpsA-J) operon is responsible for
      EPS production in V. parahaemolyticus. The expression of cpsA-J is controlled by
      ScrABC, intracellular concentration of c-di-GMP, CpsS-CpsR-CpsQ regulatory
      cascade, and quorum sensing. The data presented here showed that H-NS activates
      the EPS-dependent bacterial colony morphology and the transcription of cpsQ and
      cpsA-J. H-NS has negative regulatory activity on scrABC transcription, and
      thereby may result in enhancing the intracellular concentration of c-di-GMP.
      Thus, a regulatory circuit involved in regulating cpsA-J/EPS production by H-NS,
      ScrABC and CpsQ was identified in V. parahaemolyticus.

PMID- 29366863
TI  - Green synthesis of titanium dioxide (TiO2) nanoparticles by Trigonella foenum
      graecum extract and its antimicrobial properties.
AB  - In recent years, biosynthesis of nanoparticles has received considerable
      attention due to the growing need to develop clean and nontoxic chemicals, low
      cost approaches, eco - friendly solvents and renewable materials. In the current
      study, the biosynthesis of TiO2 nanoparticles (TiO2NPs) was attained by a
      chemical and biosynthesized method by using the aqueous leaf extract of
      Trigonella foenum-graecum (TF-TiO2NP). TiO2 NPs were characterized by FTIR, UV,
      XRD, HR-TEM and HR-SEM methods. The X-ray diffraction displayed the existence of
      TF-TiO2NPs which is confirmed by the incidence of peaks at 25.28 corresponds to
      101 anatase form. HR-SEM perceptions revealed that synthesized TiO2NPs were
      spherical in shape and the size of individual nanoparticles as well as a few
      aggregates was found to be 20-90 nm. The antimicrobial activities of
      biosynthesized nanoparticles (TF-TiO2NPs) were examined using Kirby-Bauer method.
      The TF-TiO2 nanoparticles showed significant antimicrobial activity against all
      the tested microorganisms.

PMID- 29366864
TI  - Green synthesized silver nanoparticles by marine endophytic fungus Penicillium
      polonicum and its antibacterial efficacy against biofilm forming, multidrug
      resistant Acinetobacter baumanii.
AB  - Acinetobacter baumanii, a gram-negative, non-motile, encapsulated coccobacillus
      which causes infections worldwide. The objective of this study was to find a
      fungal strain that could be utilized to biosynthesize antibacterial silver
      nanoparticles (AgNPs) against Acinetobacter baumanii. The present investigation
      explains rapid and extracellular biosynthesis of silver nanoparticles by the
      algicolous endophytic fungus, Penicillium polonicum, isolated from the marine
      green alga Chetomorpha antennina. The obtained silver nanoparticles were
      characterized by UV-Vis spectroscopy, Raman spectroscopy, Fourier transformation
      infrared (FTIR), and Transmission electron microscopy (TEM). The SNPs showed a
      characteristic UV- visible peak at 430 nm with an average size of 10-15 nm. As
      evident from the FTIR and Raman spectra, possibly the protein components of
      fungal extract have caused the reduction of silver nitrate. Parametric
      optimization, including the concentration of AgNO3, ratio of cell filtrate and
      AgNO3, fungal biomass, reaction time, pH, and presence of light, was done for
      rapid AgNPs production. The antibacterial efficacy of AgNPs against multi-drug
      resistant, biofilm-forming Acinetobacter baumanii, was evaluated by well
      diffusion assay. The Minimum inhibitory concentration (MIC) of AgNP was 15.62
      MUgml-1 and the minimum bactericidal concentration (MBC) was 31.24 MUgml-1.
      Killing kinetic assay revealed complete killing of the bacterial cells within 6
      h. Log reduction and percent survival of bacterial cells were analyzed from
      killing kinetic study. Bactericidal nature of synthesized nanoparticles was
      confirmed by fluorescent microscopical analysis. The effect of AgNPs on the
      ultrastructure of bacterial pathogen was evaluated by Transmission electron
      microscopy.

PMID- 29366866
TI  - International consensus (ICON) on audiological assessment of hearing loss in
      children.
AB  - The prevalence of hearing loss in newborns and infants is estimated between 1 to
      3.47 cases per 1000 live births. Early diagnosis and rehabilitation of congenital
      hearing loss are mandatory in order to achieve a satisfactory linguistic and
      cognitive development. Without appropriate opportunities to learn language, these
      children will fall behind their normal hearing peers in communication, cognition,
      reading and socio-emotional development. After promising results, neonatal
      screening for hearing loss and audiological evaluation are becoming more
      extensively carried out. In planning universal neonatal hearing screening
      programs, transient evoked otoacoustic emissions and auditory brainstem responses
      are the gold standard for the screening and diagnosis program. However, there is
      no consensus regarding the use of audiometry and other electrophysiological tests
      (such as auditory steady-state responses) in current practices. Several screening
      and audiological assessment procedures have been described and advocated all
      around the world. But, a systematic scheme of performing diagnosis in the
      pediatric audiology population is lacking. A consensus conference was held at the
      International Federation of Oto-rhino-laryngological Societies Congress, in June
      2017, to discuss the different current practices and to identify the best
      neonatal hearing screening and audiological assessment management. This article
      is intended to provide professionals with recommendations about the "best
      practice" based on consensus opinion of the session's speakers, and a review of
      the literature on the efficacy of various assessment options for children with
      hearing loss.

PMID- 29366865
TI  - Phytochemical analysis and antibacterial activity of methanolic extract of
      Bergenia purpurascens against common respiratory infection causing bacterial
      species in vitro and in neonatal rats.
AB  - Respiratory bacterial infections are responsible for significant mortality across
      the world and with emergence of drug resistant bacterial strains there is urgent
      need to look for new treatment options. In this study we evaluated the
      antimicrobial activity of methanolic extract of Bergenia purpurasceus in vitro
      and in neonatal rats. The results of the present study revealed that the
      methanolic extract exhibits antimicrobial activity against all the bacterial
      species with MIC ranging from 75 to 150 MUg/ml. The antibacterial activity of the
      Bergenia purpurasceus extract was also determined in the neonatal rat models
      wherein it was observed that administration of 50 and 100 mg/kg doses of Bergenia
      purpurasceus extract improved the survival of the neonatal rats infected with S.
      aureus. Furthermore, the extract showed considerable antioxidant activity which
      was positively associated with the phenolics and flavonoids content. Finally the
      constituents responsible for the bioactivity of the extract were identified and
      found to be bergenin, catechin, naringenin, myricetin and gallic acid.
      Takentogether, these results indicate that Bergenia purpurasceus extract could
      prove useful for the treatment of bacterial respiratory infections.

PMID- 29366867
TI  - Forestier syndrome and obstructive sleep apnea: Surgical treatment.
AB  - INTRODUCTION: We report a case of obstructive sleep apnea that occurred as a
      result of Forestier disease and describe the surgical treatment that was
      performed. SUMMARY: The patient is a 56-year-old man who presented dysphagia for
      solids and liquids, snoring (score 10) and excessive daytime sleepiness for 5
      years. On fiber optic laryngoscopy examination, there was interarytenoid edema
      and protrusion of the posterior wall of the larynx. The cervical X-Ray showed
      protrusion of intervertebral disc between C3-C5 (skeletal hyperostosis) and the
      polysomnography revealed apnea-hypopnea index (AHI) of 56 events/h. Surgery was
      performed by the otorhinolaryngology and orthopedic teams. The patient evolved
      with complete symptom resolution and an AHI of 3,9 events/h on the control
      polysomnography. DISCUSSIONS: This is the first reported case of Forestier
      Syndrome (FS) associated with Obstructive Sleep Apnea (OSA) that was proposed
      surgical treatment and the patient evolved with complete symptom improvement.

PMID- 29366868
TI  - In vivo assessment of the hepatotoxicity of a new Nostoc isolate from the Nile
      River: Nostoc sp. strain NRI.
AB  - Nostoc sp. is one of the most widely distributed cyanobacterial genera that
      produce potentially protein phosphatase (PP) inhibitor; microcystins (MCs). MCs
      have posed a worldwide concern due to predominant hepatotoxicity to human health.
      We have previously isolated a Nostoc strain (NR1) from the Nile River (the main
      water supply in Egypt) and this strain exerted production of rare and highly
      toxic MC; demethylated microcystin-LR. There is no data concerning risk factors
      of liver diseases for human and animal exposure to NR1-contaminated drinking
      water yet. It is thus important to evaluate acute (LD50 dose), subacute (0.01%
      and 10% of LD50 dose) and subchronic (0.01% and 10% of LD50 dose)
      hepatotoxicity's NR1 extract using experimental mice. Mice groups, who orally
      received 0.01% LD50, represented a permissible concentration of the World Health
      Organization (WHO) for MC in drinking water. Several parameters were detected,
      including hepatotoxicity (i.e. PP activity, liver function, oxidative stress
      markers and DNA fragmentation), pro-inflammatory cytokine (TNF-alpha) and liver
      histopathology. Our results demonstrated LD50 of NR1 extract was at 15,350 mg/kg
      body weight and caused hepatotoxicity that attributed to PP inhibition and a
      significant increase of hepatic damage biomarkers with lipid accumulation.
      Moreover, NR1 extract induced hepatic oxidative damage that may have led to DNA
      fragmentation and production of TNF-alpha. As demonstrated from the
      histopathological study, NR1 extract caused a severe collapse of cytoskeleton
      with subsequent focal degeneration of hepatocytes, necroinflammation and
      steatosis. The grade of hepatotoxicity in subacute (10% of LD50) group was higher
      than that in the subchronic (10% of LD50 and 0.01% of LD50, WHOch, respectively)
      groups. No significant hepatotoxicity was detectable for subacute (0.01% of LD50,
      WHOac) group. NR1 is therefore considered as one of the harmful and life
      threatening cyanobacteria for Egyptian people being exposed to dose above WHO
      guideline. Thus, biological indicators and thresholds for water treatment are
      extremely needed.

PMID- 29366870
TI  - Bioaccumulation of trace metals in banded Persian bamboo shark (Chiloscyllium
      arabicum) from the Persian Gulf: A food safety issue.
AB  - Persian bamboo shark (Chiloscyllium arabicum) was collected from two sites of the
      Khozestan province, northern basin of Persian Gulf, with the aim to identify
      differences in metal concentrations between fishing areas as well as the risk for
      human health due to consumption of the selected species. We analyzed Zn, Cu, Pb,
      Hg, Cd and Ni in muscle and liver tissues of specimens from both areas of study
      using atomic adsorption spectrometry. Statistical elaborations revealed higher
      bioaccumulation of metals in livers than muscle as well as in the site of worthy
      of Musa as regards Zn, Pb and Ni than the site of worthy of Darvis, due to the
      more intensive anthropogenic input. The risk for consumers is low for the most of
      metals, with the exception of the THQ for Hg, which resulted next to the level of
      risk with high frequencies of consumption.

PMID- 29366869
TI  - Urine biomarkers informative of human kidney allograft rejection and tolerance.
AB  - We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo
      status of human kidney allografts based on our conceptualization that the kidney
      allograft may function as an in vivo flow cell sorter allowing access of graft
      infiltrating cells to the glomerular ultrafiltrate and that interrogation of
      urinary cells is informative of allograft status. For the profiling urinary
      cells, we developed a two-step preamplification enhanced real-time quantitative
      PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating
      for the low RNA yield from urine and the customized amplicon facilitating
      absolute quantification of mRNA and overcoming the inherent limitations of
      relative quantification widely used in RT-QPCR assays. Herein, we review our
      discovery and validation of urinary cell mRNAs as noninvasive biomarkers
      prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts.
      We summarize our results reflecting the utility of urinary cell mRNA profiling
      for predicting reversal of ACR with anti-rejection therapy; differential
      diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and
      prognosis of BK virus nephropathy. Messenger RNA profiles associated with human
      kidney allograft tolerance are also summarized in this review. Altogether, data
      supporting the idea that urinary cell mRNA profiles are informative of kidney
      allograft status and tolerance are reviewed in this report.

PMID- 29366872
TI  - Calcium-binding protein, secretagogin, specifies the microcellular tegmental
      nucleus and intermediate and ventral parts of the cuneiform nucleus of the mouse
      and rat.
AB  - Secretagogin (SCGN) is a recently discovered calcium binding protein of the EF
      hand family, cloned from beta cells of pancreatic island of Langerhans and
      endocrine cells of the gastrointestinal gland. SCGN characterizes some particular
      neuron groups in various regions of the nervous system and is considered as one
      of the useful neuron subpopulation markers. In the present study we reported that
      SCGN specifically labelled a particular neuronal cluster in the brainstem of the
      mice and rats. The comparison of the SCGN immunostaining with the choline
      acetyltransferase immunostaining and acetylcholinesterase staining clearly
      indicated that the particular cluster of SCGN positive neurons corresponded to
      the microcellular tegmental nucleus (MiTg) and the ventral portion of the
      cuneiform nucleus (CnF), both of which are components of the isthmus. The
      analyses in mice indicated that SCGN positive neurons in the MiTg and CnF were
      homogeneous in size and shape, appearing to compose a single complex: their
      somata were small comparing with the adjacent cholinergic neurons in the
      pedunculotegmantal nucleus, 10.5 vs 16.0 MUm in diameter, and extended 2-3
      slender smooth processes. SCGN might be one of significant markers to reconsider
      the delineations of the structures of the mouse, and presumably rat, brainstem.

PMID- 29366871
TI  - Cytochrome P450 1A1 (CYP1A1) protects against nonalcoholic fatty liver disease
      caused by Western diet containing benzo[a]pyrene in mice.
AB  - The Western diet contributes to nonalcoholic fatty liver disease (NAFLD)
      pathogenesis. Benzo[a]pyrene (BaP), a prototypical environmental pollutant
      produced by combustion processes, is present in charcoal-grilled meat. Cytochrome
      P450 1A1 (CYP1A1) metabolizes BaP, resulting in either detoxication or metabolic
      activation in a context-dependent manner. To elucidate a role of CYP1A1-BaP in
      NAFLD pathogenesis, we compared the effects of a Western diet, with or without
      oral BaP treatment, on the development of NAFLD in Cyp1a1(-/-) mice versus wild
      type mice. A Western diet plus BaP induced lipid-droplet accumulation in liver of
      Cyp1a1(-/-) mice, but not wild-type mice. The hepatic steatosis observed in
      Cyp1a1(-/-) mice was associated with increased cholesterol, triglyceride and bile
      acid levels. Cyp1a1(-/-) mice fed Western diet plus BaP had changes in expression
      of genes involved in bile acid and lipid metabolism, and showed no increase in
      Cyp1a2 expression but did exhibit enhanced Cyp1b1 mRNA expression, as well as
      hepatic inflammation. Enhanced BaP metabolic activation, oxidative stress and
      inflammation may exacerbate metabolic dysfunction in liver of Cyp1a1(-/-) mice.
      Thus, Western diet plus BaP induces NAFLD and hepatic inflammation in Cyp1a1(-/-)
      mice in comparison to wild-type mice, indicating a protective role of CYP1A1
      against NAFLD pathogenesis.

PMID- 29366874
TI  - Novel DCC variants in congenital mirror movements and evaluation of disease
      associated missense variants.
AB  - Congenital mirror movements (CMM) are involuntary movements of one side of the
      body that mirror intentional movements of the other side. Heterozygous missense,
      frameshift and nonsense variants and small intragenic deletions in DCC cause CMM,
      isolated agenesis of the corpus callosum (ACC) or both. We report here the
      clinical phenotype and natural history of ten individuals with CMM carrying five
      different monoallelic DCC variants, including the missense variant p.(Trp273Arg),
      two duplications, one deletion and one deletion-insertion; all are novel and
      absent from databases. We re-evaluated the 15 known disease-associated DCC
      missense variants by determining minor allele frequency (MAF) and pathogenicity
      using four in silico tools combining previous pathogenicity scores and the
      ACMG/AMP standards and guidelines and classified them in three groups. Group I
      contains three DCC missense variants that are rather unlikely to be associated
      with a higher risk to CMM and/or ACC. The five variants in group II may represent
      susceptibility factors to altered midline crossing in the central nervous system.
      Group III includes seven variants absent in publically available databases and
      representing possible pathogenic alleles, with four predicted to have a severe
      impact on protein function. Based on this data and the variable expressivity and
      incomplete penetrance present in heterozygous carriers of a DCC variant,
      classification and clinical interpretation of missense variants is challenging in
      the absence of evidence of pathogenicity originated from functional studies.
      Evaluation of missense variants by MAF and a weighted combination of several
      computational algorithms is recommended.

PMID- 29366873
TI  - Modeling Marek's disease virus transmission: A framework for evaluating the
      impact of farming practices and evolution.
AB  - Marek's disease virus (MDV) is a pathogen of chickens whose control has twice
      been undermined by pathogen evolution. Disease ecology is believed to be the main
      driver of this evolution, yet mathematical models of MDV disease ecology have
      never been confronted with data to test their reliability. Here, we develop a
      suite of MDV models that differ in the ecological mechanisms they include. We fit
      these models with maximum likelihood using iterated filtering in 'pomp' to data
      on MDV concentration in dust collected from two commercial broiler farms. We find
      that virus dynamics are influenced by between-flock variation in host
      susceptibility to virus, shedding rate from infectious birds, and cleanout
      efficiency. We also find evidence that virus is reintroduced to farms
      approximately once per month, but we do not find evidence that virus sanitization
      rates vary between flocks. Of the models that survive model selection, we find
      agreement between parameter estimates and previous experimental data, as well as
      agreement between field data and the predictions of these models. Using the set
      of surviving models, we explore how changes to farming practices are predicted to
      influence MDV-associated condemnation risk (production losses at slaughter). By
      quantitatively capturing the mechanisms of disease ecology, we have laid the
      groundwork to explore the future trajectory of virus evolution.

PMID- 29366875
TI  - First prenatal case of proximal 19p13.12 microdeletion syndrome: New insights and
      new delineation of the syndrome.
AB  - Proximal 19p13.12 microdeletion has been rarely reported. Only five postnatal
      cases with intellectual disability, facial dysmorphism, branchial arch defects
      and overlapping deletions involving proximal 19p13.12 have been documented. Two
      critical intervals were previously defined: a 700 kb for branchial arch defects
      and a 350 kb for hypertrichosis-synophrys-protruding front teeth. We describe the
      first prenatal case, a fetal death in utero at 39 weeks of gestation. Agilent
      180K array-CGH analysis identified a heterozygous interstitial 745 kb deletion at
      19p13.12 chromosome region, encompassing both previously reported critical
      intervals, including at least 6 functionally relevant genes: NOTCH3, SYDE1,
      AKAP8, AKAP8L, WIZ and BRD4. Quantitative PCR showed that the deletion occurred
      de novo with a median size of 753 kb. NOTCH3 and SYDE1 were candidate genes for
      placental pathology whilst AKAP8, AKAP8L, WIZ and BRD4 were highly expressed in
      the branchial arches. Molecular characterization and sequencing of candidate
      genes for placental pathology and branchial arch defects were carried out in
      order to correlate the genotype-phenotype relationship and unravel the underlying
      mechanism of proximal 19p13.12 microdeletion syndrome. This case also contributes
      to define the novel critical interval and expand the clinical phenotype spectrum
      of proximal 19p13.12 microdeletion syndrome.

PMID- 29366876
TI  - Less Invasive Surgical Approaches for Left Ventricular Assist Device
      Implantation.
AB  - For several years, the standard implantation strategy of ventricular assist
      devices has involved a full sternotomy approach. However, less invasive
      implantation techniques are now becoming increasingly popular as they are
      associated with reduction of trauma, blood loss, and arrhythmogenic
      complications, as well as a decreased duration of intensive care unit and in
      hospital stay. Thus, due to miniaturization and increasing technical improvement
      of ventricular assist devices, less invasive strategies for implantation,
      explantation, exchange, and concomitant cardiac procedures are on the rise. In
      this review article, we report on the state of the art of less invasive
      techniques for implantation, explantation, exchange, and combined cardiac
      procedures of ventricular assist devices.

PMID- 29366877
TI  - Are universal upper reference limits for alanine aminotransferase (ALT)
      appropriate for assessing pediatric liver injury?

PMID- 29366878
TI  - Trajectories of eGFR decline over a four year period in an Indigenous Australian
      population at high risk of CKD-the eGFR follow up study.
AB  - : Being able to estimate kidney decline accurately is particularly important in
      Indigenous Australians, a population at increased risk of developing chronic
      kidney disease and end stage kidney disease. The aim of this analysis was to
      explore the trend of decline in estimated glomerular filtration rate (eGFR) over
      a four year period using multiple local creatinine measures, compared with
      estimates derived using centrally-measured enzymatic creatinine and with
      estimates derived using only two local measures. METHOD: The eGFR study comprised
      a cohort of over 600 Aboriginal Australian participants recruited from over
      twenty sites in urban, regional and remote Australia across five strata of
      health, diabetes and kidney function. Trajectories of eGFR were explored on 385
      participants with at least three local creatinine records using graphical methods
      that compared the linear trends fitted using linear mixed models with non-linear
      trends fitted using fractional polynomial equations. Temporal changes of local
      creatinine were also characterized using group-based modelling. Analyses were
      stratified by eGFR (<60; 60-89; 90-119 and >=120ml/min/1.73m2) and albuminuria
      categories (<3mg/mmol; 3-30mg/mmol; >30mg/mmol). RESULTS: Mean age of the
      participants was 48years, 64% were female and the median follow-up was 3years.
      Decline of eGFR was accurately estimated using simple linear regression models
      and locally measured creatinine was as good as centrally measured creatinine at
      predicting kidney decline in people with an eGFR<60 and an eGFR 60
      90ml/min/1.73m2 with albuminuria. Analyses showed that one baseline and one
      follow-up locally measured creatinine may be sufficient to estimate short term
      (up to four years) kidney function decline. The greatest yearly decline was
      estimated in those with eGFR 60-90 and macro-albuminuria: -6.21 (-8.20, -4.23)
      ml/min/1.73m2. CONCLUSION: Short term estimates of kidney function decline can be
      reliably derived using an easy to implement and simple to interpret linear mixed
      effect model. Locally measured creatinine did not differ to centrally measured
      creatinine, thus is an accurate cost-efficient and timely means to monitoring
      kidney function progression.

PMID- 29366879
TI  - The Waxing and Waning of Antithrombotic Therapy in Cardiovascular Disease - Where
      Is the Moon Now?

PMID- 29366880
TI  - Increased HCN Channel Activity in the Gasserian Ganglion Contributes to
      Trigeminal Neuropathic Pain.
AB  - : Orofacial neuropathic pain caused by trigeminal nerve injury is a debilitating
      condition with limited therapeutic options. Hyperpolarization-activated cyclic
      nucleotide-gated (HCN) channels regulate neuronal excitability and are involved
      in the development and maintenance of chronic pain. However, the effect of HCN
      channel activity in the Gasserian ganglion on trigeminal neuropathic pain has not
      been examined. We evaluated nociceptive behaviors after microinjection of the HCN
      channel blockers ZD7288 or ivabradine into the Gasserian ganglion in rats with
      trigeminal nerve injury. Both blockers dose-dependently ameliorated evoked and
      spontaneous nociceptive behavior in rats with trigeminal neuropathic pain.
      Moreover, the clinically available HCN channel blocker ivabradine showed a
      prolonged antinociceptive effect. In the Gasserian ganglion, HCN1 and HCN2 are
      major HCN isoforms. After trigeminal nerve injury, the counts of HCN1 as well as
      HCN2 immuno-positive punctae were increased in the ipsilateral Gasserian
      ganglions. These results indicate that the increased HCN channel activity in the
      Gasserian ganglion directly contributes to neuropathic pain resulting from
      trigeminal nerve injury. PERSPECTIVE: Trigeminal nerve damage-induced orofacial
      pain is severe and more resistant to standard pharmacological treatment than
      other types of neuropathic pain. Our study suggests that targeting HCN channel
      activities in the Gasserian ganglion may provide an alternative treatment of
      trigeminal neuropathy including trigeminal neuralgia.

PMID- 29366881
TI  - Metallic gold and bioactive quinacrine hybrid nanoparticles inhibit oral cancer
      stem cell and angiogenesis by deregulating inflammatory cytokines in p53
      dependent manner.
AB  - Complete eradication of aggressive oral cancer remains a challenge due to the
      presence of CSCs. They resist conventional chemotherapeutic agents due to their
      self-renewal, drug efflux, and efficient DNA repair capacity. Here, we formulated
      a hybrid-nanoparticle (QAuNP) using quinacrine and gold and
      characterized/investigated its anti-angiogenic and anti-metastatic effect on OSCC
      CSCs. QAuNP significantly inhibited cellular proliferation, caused apoptosis in
      vitro, and disrupted angiogenesis in vivo and tumor regression in xenograft mice
      model. It not only inhibited crucial angiogenic markers Ang-1, Ang-2 and VEGF but
      also depleted MMP-2 in H-357-PEMT cells in a p53 and p21-dependent manner. QAuNP
      also increased the ROS and NO generation in OSCC-CSCs and reduced the
      mitochondrial membrane potential. It altered the level of inflammatory cytokines
      IL-6, IL-1beta, TNF-alpha and metastasis-associated markers (CD-44, CD-133) in H
      357-PEMT and CM-treated endothelial cells (HUVEC) in p53/p21-dependent manner.
      Therefore, QAuNP will be a useful therapeutic agent against metastatic OSCC.

PMID- 29366882
TI  - Threocytidines: Insight into the Conformational Preferences of Artificial Threose
      Nucleic Acid (TNA) Building Blocks in B3LYP Studies.
AB  - A systematic DFT conformational studies of four building blocks of TNA with
      cytosine attached to the C1' atom of the alpha-L-threofuranose moiety are
      presented. Structures bearing 2'-OR and 3'-OR substituents, where R represents H,
      CH3 and phosphate groups, were used in the studies using a B3LYP functional in
      the gas phase. The chi angle (C2-N1-C1'-O4'), the nu0-nu4 endocyclic torsion
      angles and the exocyclic torsion angles epsilon (X-O2'-C2'-C1') and gamma (X-O3'
      C3'-C2') geometry parameter variations were taken into consideration. Three
      energy minima, high-anti, anti and syn, were found for the rotation about the C1'
      N1 bond. The high-anti orientation of the base with respect to the sugar moiety,
      turned out to be preferred, regardless of the substituents at the C2' and C3'
      positions. Other orientations are at least 1.65 kcal/mol higher in Gibbs free
      energy than the high-anti one. It has been shown that intramolecular H-bonds and
      the anomeric effect of phosphate groups strongly affect the conformational
      preferences of the studied compounds. Further, the structure of substituents
      attached to the sugar moiety influence the pucker of the furanoid ring. The
      furanoid ring in the global minima of the compound with two OH groups (TC1) in
      the 2' and 3' positions, and the compound having a 3'-phosphate group (TC2),
      adopt roughly the same conformation located at the southern range of the
      pseudorotation wheel, and thus are close to those found in the B type DNA helix.
      The low-energy high-anti rotamers of the geometry with the phosphate group
      attached to the sugar ring in the 2' position (TC3) and the geometry with two
      methoxyl groups (TC4) have their furanoid rings in conformations resembling those
      found in A DNA and RNA helices (the northern range of the pseudorotation wheel).

PMID- 29366883
TI  - beta-Alanine mediated inhibition of PTHR1suppresses the proliferation, invasion
      and tumorigenesis in metastatic human osteosarcoma U2OS cells.
AB  - The present study was aimed to investigate the effect of beta-alanine mediated
      inhibition of parathyroid hormone 1 receptor (PTHR1), suppresses the
      proliferation, invasion, and tumorigenesis in metastatic human osteosarcoma U2OS
      cells. Cell survival rate was reduced 96.54, 91.23, 84.62, 76.42 and 69.72%
      following incubation of beta-alanine at 50-250 mM respectively. Annexin
      V/propidium iodide (PI) staining showed a reduced level of viable cells (71.37%)
      at 250 mM of beta-alanine. U2OS cell proliferation, adhesion, invasion, and
      migration were decreased following incubation with beta-alanine. Matrix
      metalloproteinases-2/9 (MMP-2/9) mRNA expression was reduced, whereas tissue
      inhibitors of metalloproteinases-1/2 (TIMP-1/2) mRNA expression was increased
      remarkably. The mRNA and protein of PTHR1 were reduced in the cells following
      incubation with beta-alanine. Vacuole membrane protein 1 (Vmp1) mRNA and protein
      were increased in the cells following incubation with beta-alanine. In tunel
      assay, the number of PTHR1 positive cells was 67, 34 and 17 following incubation
      with beta-alanine at 150, 200 and 250 mM respectively. Taking all these data
      together, it is concluded that beta-alanine mediated inhibition of PTHR1 reduced
      the U2OS cell proliferation, invasion, migration, and tumorigenesis. Furthermore,
      the results indicated that the beta-alanine induced expression of PTHR1 has a
      positive relationship with invasion and metastasis of osteosarcoma cells.

PMID- 29366884
TI  - alpha- and beta-d-Glucans from the edible mushroom Pleurotus albidus
      differentially regulate lipid-induced inflammation and foam cell formation in
      human macrophage-like THP-1 cells.
AB  - Macrophages play an essential role in lipid metabolism; however, the excessive
      uptake of modified lipids and cholesterol crystals (CC) leads to the formation of
      pro-inflammatory lipid-laden macrophages called foam cells. Since the alpha-1,6-
      and beta-1,3-d-glucans from the basidiome and the mycelium of the edible mushroom
      Pleurotus albidus have previously been shown to regulate macrophage function,
      these glucans were tested in macrophage-like THP-1 cells previously exposed to
      acetylated low-density lipoproteins (acLDL) or CC. The glucans inhibited lipid
      induced inflammation, but only the beta-1,3-d-glucan regulated both the NLRP3
      inflammasome activation and the expression of genes involved on lipid efflux in
      acLDL- or CC-pretreated cells, thereby reducing foam cell formation. In contrast,
      the two alpha-1,6-glucans tested inhibited foam cell formation only in acLDL
      pretreated cells and had no effect on the expression of the peroxisome
      proliferator-activated receptor gamma and liver X receptor alpha genes,
      suggesting that these glucans regulate lipid influx rather than lipid efflux.
      Thus, alpha- and beta-d-glucans differentially regulate lipid-induced
      inflammation and foam cell formation in macrophage-like cells. Furthermore,
      results emphasize that P. albidus has potential to be used as a functional food
      or as a source for the extraction of biologically-active glucans.

PMID- 29366885
TI  - Enzymatic degradation of poly(butylene succinate) with different molecular
      weights by cutinase.
AB  - Poly(butylene succinate) (PBS) films with different molecular weights were
      enzymatically degraded by cutinase. Changes in the properties of the films before
      and after enzymatic degradation were studied through scanning electron
      microscopy, differential scanning calorimetry, thermogravimetry, X-ray powder
      diffraction, proton nuclear magnetic resonance, and gel-permeation chromatography
      analysis. The weight loss of the films initially decreased and then increased
      with increasing molecular weight. Crystallinity was inversely proportional to
      weight loss and tended to decrease with prolonged degradation time. Crystalline
      and amorphous regions were simultaneously degraded. The thermal stability of PBS
      films decreased after enzymatic degradation. PBS was the main component of the
      enzymatically degraded polymers. The molecular weights of the films did not
      considerably change before and after degradation by cutinase.

PMID- 29366886
TI  - Extraction and characterization of chitosan from prawn shell waste and its
      conjugation with cutinase for enhanced thermo-stability.
AB  - The present article describes extraction of chitosan from prawn shells waste and
      its application in thermal stabilization of Fusarium sp. ICT SAC1 cutinase by non
      covalent and covalent conjugation. Extracted chitosan represented 78.40% degree
      of deacetylation (DDA), a molecular weight of 173 kDa and was soluble in 1%
      acetic acid with 2.8 +/- 0.15% insoluble matter. The structural (FTIR, NMR and
      XRD) and thermal characterization (DSC and TGA) indicated unique properties for
      chitosan. Plausible chitosan structure was also deduced. The water and fat
      binding capacities were 923% and 598.05% while 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid) and 1,1-diphenyl-2-picrylhydrzyl radicals
      scavenging activity was 60.62 and 11.83 MUM Trolox-Equivalent/ml. The Km and Vmax
      values of free cutinase were 0.82 mM and 20.64 mM/min which increased by 14.63
      and 17.07%; and 27.18 and 43.94% after non-covalent and covalent conjugation,
      respectively. A marginal increment in thermal inactivation constants and energy
      (kd, t1/2, D and Ed value) were also noticed for cutinase-chitosan conjugates.
      The enthalpy, free energy and entropy values increased marginally in covalent
      conjugate vis-a-vis non-covalent conjugated and free cutinase. A reduction in
      alpha-helix, random coils and beta-sheets content was noted after conjugation.

PMID- 29366887
TI  - Effective adsorption of oil droplets from oil-in-water emulsion using metal ions
      encapsulated biopolymers: Role of metal ions and their mechanism in oil removal.
AB  - Herein, synthesized and compared the three different kinds of hybrid bio
      polymeric composites viz., lanthanum embedded chitosan/gelatin (La@CS-GEL),
      zirconium embedded chitosan/gelatin (Zr@CS-GEL) and cerium embedded
      chitosan/gelatin (Ce@CS-GEL) in terms of their oil uptake efficiency. The
      adsorption efficiency was studied under various optimized parameters like contact
      time, pH, dose, initial oil concentration and temperature. The oil adsorption
      capacity was found to be 91, 82 and 45% for La@CS-GEL, Zr@CS-GEL and Ce@CS-GEL
      composites respectively. The metals were used as a bridging material to connect
      both CS and GEL using the hydrophilic groups to enhance the oil recovery by
      hydrophobic interaction. Also, the introduction of metal ions on the surface of
      biopolymers would modify the oil/water properties which in turn, decrease the
      interfacial tension between oil and water phases. The mechanism of oil uptake was
      explained using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction
      (XRD), thermogravimetric analysis (TGA), scanning electron microscope (SEM),
      energy dispersive X-ray (EDAX) and heat of combustion. The experimental data
      confirmed Langmuir isotherm as the best fit for oil adsorption process.
      Thermodynamic parameters such as standard free energy (DeltaG degrees ), standard
      enthalpy (DeltaH degrees ) and standard entropy (DeltaS degrees ) indicated that
      the oil adsorption was spontaneous and endothermic. The oil adsorption mechanism
      was established based on isotherm and thermodynamic models.

PMID- 29366888
TI  - Carboxymethyl cellulose macromolecules as generator of anisotropic nanogold for
      catalytic performance.
AB  - Morphological structure and size of Au nanoparticles (AuNPs) are basically
      affected on their chemical reactivity which are influenced by preparation method
      due to including different materials and may cause some interferences in their
      reactivity. Hence, current work focused on preparation of anisotropic AuNPs with
      astonishing catalytic reactivity, using carboxymethyl cellulose (CMC)
      macromolecules, as generator and shape conductor. Geometrical shape and size
      distribution of the so-obtained AuNPs were found to be dependent on CMC
      concentration and addition of alkali. By using 2 g/L CMC, sharp and quite intense
      SPR peak was observed for the spherical AuNPs with size of 8.8-14.0 nm. While,
      agglomerated Au particles with larger size (432.4-488.3 nm) showed broader
      Surface Plasmon Resonance peak in case of alkali addition. Using lower
      concentration of CMC (1 g/L) resulted in formation of heterogeneous shapes (nano
      prism and nano-hexagonal). The small sized Au nano-spheres were shown to exhibit
      the highest catalytic action. The p-nitro-aniline was fully reduced to p-amino
      aniline in only 1 min and achieved rate constant of 649.2 * 10-3 s-1. This work
      offers a unique, simple and green methodology to prepare catalytically active
      anisotropic AuNPs which could be highly applicable in different purposes.

PMID- 29366889
TI  - Is perturbation in the quaternary structure of bacterial CysE, another regulatory
      mechanism for cysteine synthesis?
AB  - Drug resistance to almost all antibiotics of Shigella flexneri, a major cause of
      shigellosis in developing countries, necessitates continuous discovery of novel
      therapeutics. This study reports a structure-function analysis of a potential
      drug target serine acetyltransferase (CysE), an enzyme of de novo cysteine
      biosynthesis pathway that is absent in humans. Analysis of CysE sequences of S.
      flexneri species and serotypes displayed only two variants that differed by a
      single amino acid substitution at position 241. Structural inspection of the
      available crystal structure disclosed this site to be distinct from the
      substrate/cofactor binding pockets or dimer/trimer interfaces. This study
      discovers that V241 variant of S. flexneri CysE has nearly null enzymatic
      activity. The observation is explained by molecular dynamic studies which reveal
      that the disorder generated by A241V substitution is the basis of dissociation of
      the quaternary assembly of S. flexneri CysE leading to loss of enzymatic activity
      and stability. The study provides the first evidence that position 241 of CysE,
      affects the catalytic efficiency of enzyme and suggests this locus as a 'hot
      spot' for the propagation of conformational changes. It may be postulated that
      transient quaternary structure of CysE maybe another mechanism for regulating the
      intracellular level of cysteine.

PMID- 29366890
TI  - SS-mPEG chemical modification of recombinant phospholipase C for enhanced thermal
      stability and catalytic efficiency.
AB  - PEGylation is one of the most promising and extensively studied strategies for
      improving the properties of proteins as well as enzymic physical and thermal
      stability. Phospholipase C, hydrolyzing the phospholipids offers tremendous
      applications in diverse fields. However, the poor thermal stability and higher
      cost of production have restricted its industrial application. This study focused
      on improving the stabilization of recombinant PLC by chemical modification with
      methoxypolyethylene glycol-Succinimidyl Succinate (SS-mPEG, MW 5000). PLC gene
      from isolate Bacillus cereus HSL3 was fused with SUMO, a novel small ubiquitin
      related modifier expression vector and over expressed in Escherichia coli. The
      soluble fraction of SUMO-PLC reached 80% of the total recombinant protein. The
      enzyme exhibited maximum catalytic activity at 80  degrees C and was relatively
      thermostable at 40-70  degrees C. It showed extensive substrate specificity
      pattern and marked activity toward phosphatidylcholine, which made it a typical
      non-specific PLC for industrial purpose. SS-mPEG-PLC complex exhibited an
      enhanced thermal stability at 70-80  degrees C and the catalytic efficiency
      (Kcat/Km) had increased by 3.03 folds compared with free PLC. CD spectrum of SS
      mPEG-PLC indicated a possible enzyme aggregation after chemical modification,
      which contributed to the higher thermostability of SS-mPEG-PLC. The increase of
      antiparallel beta sheets in secondary structure also made it more stable than
      parallel beta sheets. The presence of SS-mPEG chains on the enzyme molecule
      surface somewhat changed the binding rate of the substrates, leading to a
      significant improvement in catalytic efficiency. This study provided an insight
      into the addition of SS-mPEG for enhancing the industrial applications of
      phospholipase C at higher temperature.

PMID- 29366891
TI  - Identification of chitosan oligosaccharides binding proteins from the plasma
      membrane of wheat leaf cell.
AB  - Chitosan oligosaccharides (COS) have the ability to improve plant resistance to
      pests and diseases through activating plant immune system. However, it remains
      unclear whether stimulating reason of COS was associated with the plasma membrane
      proteins. Here, the interaction of COS with wheat leaf cell demonstrated that
      fluorescence-labeled COS were enriched on the cell surface and the interaction of
      COS with plasma membrane proteins was confirmed by quartz crystal microbalance
      (QCM) biosensor. What's more, HPLC and SDS-PAGE analysis showed that COS binding
      proteins exhibited more than three peaks and the molecular weight were 66 kDa to
      97 kDa, where the COS binding proteins were fished out from wheat plasma membrane
      proteins by the COS affinity column. More importantly, LC-MS/MS analysis
      demonstrated that several candidates, including W5G2U8_WHEAT (a potential wall
      associated receptor kinase protein), W5HY42_WHEAT and W5I0R4_WHEAT (potential G
      type lectin S-receptor-like serine/threonine-protein kinase), have the potential
      to be COS receptors.

PMID- 29366892
TI  - Design and fabrication of pectin-coated nanoliposomal delivery systems for a
      bioactive polyphenolic: Phloridzin.
AB  - Nanostructured colloidal delivery systems comprising of pectin-coated
      nanoliposomes (pectonanoliposomes) were developed as carriers for a bioactive
      polyphenolic compound (phloridzin). Phloridzin-loaded nanoliposomes were
      fabricated using a heating-stirring-sonication method, and coated with low
      methoxyl pectin using an electrostatic deposition approach. Dynamic light
      scattering, micro-electrophoresis, atomic force microscopy, and UV-Visible
      spectroscopy were used to investigate the impact of system composition on the
      size, charge, morphology and stability as well as immobilization, adsorption and
      encapsulation efficiencies of the pectonanoliposomes. Response surface
      methodology was used to optimize the composition of the pectonanoliposomes based
      on particle size and charge characteristics. Linear, quadratic and interaction
      effects of 1,2-dioleoyl-3-trimethyl ammonium propane/lecithin,
      phloridzin/lecithin and pectin/liposome ratios significantly influenced the mean
      hydrodynamic diameter and/or surface charge of pectonanoliposomes. Second-order
      polynomial regression models were generated for intensity-weighted particle size
      and zeta potential of the designed carriers. Topographic and phase contrast
      images showed that pectonanoliposomes exhibited a range of different
      morphologies. Coating the nanoliposomes with pectin improved their immobilization
      and encapsulation efficiencies as well as physical storage stability. Cationic
      pectonanoliposomes were superior to plain systems regarding long-term stability.
      Our results suggest that pectonanoliposomes may be suitable delivery systems for
      polyphenolic nutraceuticals, such as phloridizin, in functional food and
      pharmaceutical applications.

PMID- 29366893
TI  - Molecular characterization of Cry1D-133 toxin from Bacillus thuringiensis strain
      HD133 and its toxicity against Spodoptera littoralis.
AB  - Bacillus thuringiensis subsp. aizawai strain HD133, known by its effectiveness
      against Spodoptera species, produces bipyramidal crystals encompassing the
      insecticidal proteins Cry1Ab, Cry1Ca and Cry1D-133 in the proportions 60:37:3,
      respectively. In this study, we dealt with the relevance of the low rate of Cry1D
      133. The cry1D-133 gene from HD133 was cloned and sequenced. Both nucleotide and
      amino acid sequence similarity analyses with the cry1D genes available in the
      GenBank database revealed that cry1D-133 is a new variant of cry1Da-type genes
      with 99% identity with cry1Da1. Molecular modeling of the Cry1D-133 toxin showed
      that its higher toxicity is correlated to a higher number of toxin-receptor
      interactions. Optimal culture conditions of 4 h post-induction time, 160 rpm
      agitation and 37  degrees C post-induction temperature were determined and
      adopted to overproduce Cry1D-133 toxin at adequate amounts to carryout bioassays.
      A gradual increase of the proportion of Cry1D-133 to the HD133 insecticidal
      proteins forming the crystal (Cry1D-133, Cry1Ca and Cry1Ab) showed an improvement
      of the toxicity against Spodoptera littoralis larvae. Therefore, the potential of
      Cry1D-133 to enhance HD133 toxicity could promote its combination with other B.
      thuringiensis insecticidal proteins toxins in order to increase target range or
      to delay the emergence of resistance.

PMID- 29366894
TI  - Glycation of whey proteins: Technological and nutritional implications.
AB  - Whey proteins are globular proteins that have received much attention due to
      their high nutritional value and characteristic functional properties. In
      addition to being part of the protein system in milk, they constitute the main
      proteins in whey and whey protein products. Interaction of whey proteins with
      reducing sugars and carbohydrates via Maillard reaction have been extensively
      studied in milk and in model systems. Glycation of individual whey proteins
      results in variable increases in their solubility, thermal stability, antioxidant
      activity, and emulsion and foam stabilization. Limited glycation of whey protein
      products particularly whey protein isolates (WPI) using polysaccharides has been
      studied with the aim to produce conjugates with modified functional properties
      and acceptable sensory properties. An overview is presented here on the effect of
      glycation on individual whey proteins and whey protein products and the potential
      uses of the glycated whey proteins.

PMID- 29366895
TI  - Physicochemical, functional and rheological investigation of Soymida febrifuga
      exudate gum.
AB  - Acacia gum is a well-known and most used exudate gum. High solubility with low
      viscosity is one of the best property of this gum. Many studies were conducted to
      find out a substitute for acacia gum but very few gum had shown properties as
      good as acacia gum. The exudates collected from Soymida febrifuga also shows high
      solubility with low viscosity as acacia gum. Purified Soymida febrifuga gum (SFG)
      was characterised for physicochemical, functional, rheological and thermal
      properties. The FTIR spectra of SFG revealed a typical trend of polysaccharides.
      The monosaccharide composition of the gums indicated the presence arabinose,
      galactose, and ribose. Element composition of SFG shows resemblance with AG.
      However, the molecular weight of SFG is less than the AG. The rheological outcome
      was derived from flow curve measurements of gum at different concentrations and
      temperatures. Alikeness was observed in Viscosity profile of both the gums. SFG
      shows semblance with AG and can be use in food and pharmaceutical industry.

PMID- 29366896
TI  - Preparation and characterization of nano-SiO2 reinforced gelatin-k-carrageenan
      biocomposites.
AB  - The main goal of this study was to prepare bionanocomposites by combination of
      gelatin (10% w/v), k-carrageenan (0.5%) and nano-SiO2 (1, 3 or 5%). Then,
      mechanical properties (tensile strength, elongation at break, Young's modulus),
      gas permeability (water vapor, oxygen), water solubility, color, UV-vis
      transmission/absorbance, water vapor adsorption isotherms and Fourier transform
      infrared (FTIR) analysis of nanocomposites were evaluated. As the results
      indicated, inclusion of nano-SiO2 (at each level) could increase tensile strength
      and Young's modulus significantly, with the latter becoming nearly 110% higher at
      5% nanoparticle level compared with gelatin-carrageenan biocompostes.
      Furthermore, incorporation of 5% nano-SiO2 could decrease water vapor
      permeability of biocomposites from 8.9 to 1.6 * 10-11 g m-1 s-1 Pa-1 and their
      oxygen permeability from 226 to 97 cm3 MUm m-2 day-1 atm-1. Water vapor
      adsorption isotherms revealed that the water activity of 0.5 was the critical
      point beyond which the difference in equilibrium moisture content between
      nanoparticle-incorporated films and biocomposites increased considerably.
      Besides, this research demonstrated that including 5% of nano-SiO2 is a good
      solution to delay UV light driven reactions as it elevated absorbance of UV light
      (220 nm) by biocomposites up to 4 times.

PMID- 29366897
TI  - A low-molecular-weight galactofucan from the seaweed, Spatoglossum schroederi,
      binds fibronectin and inhibits capillary-like tube formation in vitro.
AB  - A low-molecular-weight (LMW) heterofucan (designated fucan B) was obtained from
      the brown seaweed, Spatoglossum schroederi, and its activity as an inhibitor of
      capillary-like tube formation by endothelial cells (ECs) was analyzed. Chemical,
      infrared and electrophoretic analyses confirmed the identity of fucan B. In
      contrast to other LMW fucans, fucan B (0.012-0.1 mg/mL) inhibited ECs capillary
      like tube formation in a concentration-dependent manner. In addition, fucan B
      (0.01-0.05 mg/mL) did not affect ECs proliferation. Fucan B also inhibited ECs
      migration on a fibronectin-coated surface, but not on laminin- or collagen-coated
      surfaces. Biotinylated fucan B was used as a probe to identify its localization.
      Confocal microscopy experiments revealed that biotinylated fucan did not bind to
      the cell surface, but rather only to fibronectin. Our findings suggest that fucan
      B inhibits ECs capillary-like tube formation and migration by binding directly to
      fibronectin and blocking fibronectin sites recognized by cell surface ligands.
      However, further studies are needed to evaluate the in vivo effects of fucan B.

PMID- 29366898
TI  - Structural elucidation and antioxidant activity of an arabinogalactan from the
      leaves of Moringa oleifera.
AB  - A novel arabinogalactan (MOP-1) was isolated from leaves of Moringa oleifera and
      was purified by macro-porous resin, DEAE-52 Cellulose and Sepharose 6B gel
      filtration chromatography. High performance gel permeation chromatography (HPGPC)
      analysis showed that the molecular weight of MOP-1 was 7.65 * 107 Da.
      Monosaccharide composition analysis indicated that sugar composition is Rha: Ara:
      Gal in a molar ratio of 1:7.32:12.12. Structural analysis indicated that MOP-1
      has a backbone of ->1)-beta-d-Galp-(3,4-> with highly branched chains at O-4
      position. The branches were composed of ->1)-beta-d-Galp-(4->, ->1)-alpha-d-Galp
      (2->, Araf-(1->, Galp-(1->. Its antioxidant activities were evaluated by DPPH
      radical scavenging capacity, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)
      (ABTS) radical cation scavenging capacity, and ferric-reducing antioxidant power
      (FRAP). The results indicated MOP-1 exhibited significant antioxidant activities.

PMID- 29366899
TI  - Inulin based glutathione-responsive delivery system for colon cancer treatment.
AB  - Colorectal cancer is one of the most common types of tumor in the world. Here we
      developed a lipoic acid esterified polysaccharide (inulin) delivery system for
      tanshinone IIA to treat colorectal cancer in vitro. The release of tanshinone IIA
      in the system was highly responsive to glutathione, which is commonly abundant in
      cancer cells. In addition, this drug delivery system was proliferative to
      Bifidobacterium longum, the common inhabitant of human intestine. Thus, this
      strategy might be useful to improve colon cancer therapy efficacy of anticancer
      drugs and meanwhile promote the growth of beneficial commensal flora in the gut.

PMID- 29366900
TI  - Starch-based polyurethane/CuO nanocomposite foam: Antibacterial effects for
      infection control.
AB  - In the present study, a new method for the synthesis of the open cell flexible
      polyurethane foams (PUFs) was developed by using starch powder and the
      modification of closed cell foam formulation. Starch is the second largest
      polymeric carbohydrate as a macromolecule on this planet with a large number of
      glucose units. Copper oxide nanoparticles (CuO NPs) were synthesized by thermal
      degradation method at different temperatures of 400, 600 and 800  degrees C as
      antimicrobial agents. The antimicrobial activity of CuO NPs and commercial CuO
      powder against the main causes of hospital infections were tested. CuO600 was the
      most effective antimicrobial agent and enhanced polymer matrix tensile strength
      with starch powder as new polyurethane foams (PUFs) cell opener with high tensile
      strength. The effects of parameters on tensile strength were optimized using
      response surface methodology (RSM). CuO NPs and PUF had optimal conditions and
      were characterized by X-ray diffraction (XRD), transmission electron microscopy
      (TEM), scanning electron microscopy (SEM) and Fourier transform infrared
      spectroscopy (FT-IR). Foam synthesized at the optimal conditions had an open cell
      structure with high tensile strength and efficient antimicrobial activity that
      made them suitable to be used as an antimicrobial hospital mattress to control
      hospital infections.

PMID- 29366901
TI  - Effects of high hydrostatic pressure on structural and physical properties of
      nisin-SPI film.
AB  - The objective of this paper is to explore the effects of high hydrostatic
      pressure (HHP) treatments on the structural and physical properties of nisin-soy
      protein-isolate (SPI) films by scanning electron microscopy (SEM), Fourier
      transformed infrared (FTIR) spectroscopy, circular dichroism (CD) spectroscopy,
      UV-Vis spectrophotometry, texture analyzer and rotational rheometer. It was found
      that the nisin-SPI based films treated by high HHP had uniform and smooth
      appearance and compact internal structures. Moreover, HHP treatment significantly
      improved the barrier and mechanical properties of the composite films. FTIR and
      CD analyses suggested that HHP treatments resulted in partial unfolding of
      protein molecules, which were supposed to lead to the improved structural and
      physical characteristics of the nisin-SPI films. Rheological analysis showed that
      all film-forming suspensions exhibited pseudo-plastic behavior, and HHP treatment
      significantly decreased the viscosity of the film-forming suspensions. Such
      effects were considered to contribute to finer structure and improved properties
      of the HHP films. The current results indicated that the structural
      transformation of SPI aggregates induced by HHP treatments introduced the changes
      in structural and physical properties of the films.

PMID- 29366902
TI  - PEP-1-glutaredoxin-1 induces dedifferentiation of rabbit articular chondrocytes
      by the endoplasmic reticulum stress-dependent ERK-1/2 pathway and the endoplasmic
      reticulum stress-independent p38 kinase and PI-3 kinase pathways.
AB  - Glutaredoxin-1 (GRX-1), belonging to the oxidoreductase family, is a component of
      the endogenous antioxidant defense system. In this study, we evaluated the
      effects of PEP-1-GRX-1 in rabbit articular chondrocytes. We found that PEP-1-GRX
      1 causes a loss of the differentiated chondrocyte phenotype. PEP-1-GRX-1-treated
      cells exhibited decreases in type II collagen expression and sulfated
      proteoglycan synthesis in a dose- and time-dependent manner. PEP-1-GRX-1 causes
      endoplasmic reticulum (ER)-stress, as evidenced by increases in ER stress marker
      proteins, i.e., glucose-regulated protein (GRP) 78, GRP 94, and phospho
      eukaryotic initiation factor 2 (eIF2) alpha. These effects were inhibited by ER
      stress inhibitors. PEP-1-GRX-1 increased the phosphorylation of Akt,
      extracellular signal-regulated kinase (ERK)-1/2, and p38. Inhibition of ERK-1/2
      by PD98059 prevented PEP-1-GRX-1-induced dedifferentiation and inhibited ER
      stress. The blockage of PI-3K/Akt or p38 kinase with SB203580 and LY294002
      accelerated PEP-1-GRX-1-induced dedifferentiation, but did not have any effect on
      PEP-GRX-1-induced ER stress. Our results indicate that the ERK-1/2 pathway
      mediates chondrocyte dedifferentiation by PEP-GRX-1-induced ER stress. The PI-3K
      and p38 kinase pathways regulate PEP-1-GRX-1-induced chondrocyte
      dedifferentiation by an ER stress-independent pathway.

PMID- 29366903
TI  - Design of psyllium-g-poly(acrylic acid-co-sodium acrylate)/cloisite 10A semi-IPN
      nanocomposite hydrogel and its mechanical, rheological and controlled drug
      release behaviour.
AB  - Soft biomaterials derived from polysaccharides are generally suffers from lack of
      mechanical robustness and instability. The naturally occurring highly abundance
      low cost polysaccharide has immense aspect as biomaterial after functionalization
      which can be designed as stretchable and rubber-like elastic with reversible
      ductility. A highly swellable, stretchable, low creep, non-cytotoxic
      nanocomposite hydrogel has been fabricated by simple one-pot Michael type
      covalent grafting of acrylic acid based copolymer onto psyllium biomacromolecular
      chian by free radical gelation technique. The fabricated hydrogel was
      rheologically tested which implies its viscoelastic and thixotropic like
      features. The porous morphology of the hydrogel was confirmed by scanning
      electron micrograph. The cryo-transmission electron micrograph shows the random
      dispersion of the nanoclay (cloisite 10A) tactoids in exfoliated as well
      intercalated forms. These random distributions of clay nanosheets also enhance
      the mechanical toughness and reversible ductility of the hydrogels which was also
      supported by the mechanical and loading-unloading cycle measurement. Nonetheless,
      the nanocomposite hydrogel was non-cytotoxic against human cell-line (human
      osteosarcoma) and shows good cell attachment of live cells in a 5-day 'live-dead'
      assay with almost negligible quantity of cell death. These attributes can promote
      this material as a soft biomaterial for controlled release device with mechanical
      robustness and rubber-like elasticity.

PMID- 29366904
TI  - Expression and function of connexin 43 protein in mouse and human retinal pigment
      epithelial cells as hemichannels and gap junction proteins.
AB  - The changes in the transport function of the outer blood-retinal barrier (BRB),
      formed by retinal pigment epithelial (RPE) cells, under pathological conditions
      need to be understood to normalize the retinal homeostasis in retinal diseases.
      Connexin 43 (Cx43) is known to be one of the basic units of gap junctions and
      hemichannels, which are opened by changes in extracellular conditions. The
      purpose of this study was to clarify the expression of Cx43 in RPE cells of the
      retina and Cx43 contribution to compound transport functions in RPE cells.
      Immunohistochemistry using guinea pig-derived polyclonal anti-Cx43 antibodies
      indicated that Cx43 is localized at the apical and intercellular membrane of
      mouse RPE cells. In addition, the immunoprecipitation study using the anti-Cx43
      antibodies suggested that Cx43 at the intercellular membrane is associated with
      gap and adherent junctions in mouse RPE cells. The intercellular transfer after
      scrape loading of Lucifer Yellow (457 g/mol) among a human RPE cell line, ARPE-19
      cells, was greater than that of fluorescein isothiocyanate-dextran (~3000 g/mol).
      This Lucifer Yellow transfer was significantly inhibited by carbenoxolone, a
      connexin inhibitor, suggesting that connexins take part in compound transfer via
      gap junctions. In addition, Lucifer Yellow uptake by ARPE-19 cells in the absence
      of extracellular Ca2+, which is a condition of hemichannel opening, was increased
      compared with that under normal conditions. This uptake of Lucifer Yellow in the
      absence of extracellular Ca2+ was significantly reduced in the presence of
      hemichannel inhibitors and Cx43-gene silencing conditions. This study suggests
      the involvement of Cx43 in dye transfer via gap junctions among RPE cells and
      hemichannel-mediated compound transport between the neural retina and RPE cells.

PMID- 29366905
TI  - Hand dysfunction in type 2 diabetes mellitus: Systematic review with meta
      analysis.
AB  - BACKGROUND: People with type 2 diabetes mellitus frequently show complications in
      feet and hands. However, the literature has mostly focused on foot complications.
      The disease can affect the strength and dexterity of the hands, thereby reducing
      function. OBJECTIVES: This systematic review and meta-analysis focused on
      identifying the existing evidence on how type 2 diabetes mellitus affects hand
      strength, dexterity and function. METHODS: We searched MEDLINE via PubMed,
      CINHAL, Scopus and Web of Science, and the Cochrane central register of
      controlled trials for reports of studies of grip and pinch strength as well as
      hand dexterity and function evaluated by questionnaires comparing patients with
      type 2 diabetes mellitus and healthy controls that were published between 1990
      and 2017. Data are reported as standardized mean difference (SMD) or mean
      difference (MD) and 95% confidence intervals (CIs). RESULTS: Among 2077 records
      retrieved, only 7 full-text articles were available for meta-analysis. For both
      the dominant and non-dominant hand, type 2 diabetes mellitus negatively affected
      grip strength (SMD: -1.03; 95% CI: -2.24 to 0.18 and -1.37, -3.07 to 0.33) and
      pinch strength (-1.09, -2.56 to 0.38 and -1.12, -2.73 to 0.49), although not
      significantly. Dexterity of the dominant hand did not differ between diabetes and
      control groups but was poorer for the non-dominant hand, although not
      significantly. Hand function was worse for diabetes than control groups in 2
      studies (MD: -8.7; 95% CI: -16.88 to -1.52 and 4.69, 2.03 to 7.35). CONCLUSION:
      This systematic review with meta-analysis suggested reduced hand function,
      specifically grip and pinch strength, for people with type 2 diabetes mellitus
      versus healthy controls. However, the sample size for all studies was low. Hence,
      we need studies with adequate sample size and randomized controlled trials to
      provide statistically significant results.

PMID- 29366906
TI  - Intratumor heterogeneity in epigenetic patterns.
AB  - Analogous to life on earth, tumor cells evolve through space and time and adapt
      to different micro-environmental conditions. As a result, tumors are composed of
      millions of genetically diversified cells at the time of diagnosis. Profiling
      these variants contributes to understanding tumors' clonal origins and might help
      to better understand response to therapy. However, even genetically homogenous
      cell populations show remarkable diversity in their response to different
      environmental stimuli, suggesting that genetic heterogeneity does not explain the
      full spectrum of tumor plasticity. Understanding epigenetic diversity across
      cancer cells provides important additional information about the functional state
      of subclones and therefore allows better understanding of tumor evolution and
      resistance to current therapies.

PMID- 29366907
TI  - Electrodiagnostic applications of somatosensory evoked high-frequency EEG
      oscillations: Technical considerations.
AB  - INTRODUCTION: High frequency oscillations (HFOs) embedded within the
      somatosensory evoked potential (SEP) are not routinely recorded/measured as part
      of standard clinical SEPs. However, HFOs could provide important additional
      diagnostic/prognostic information in various patient groups in whom SEPs are
      tested routinely. One area is the management of patients with hypoxic ischaemic
      encephalopathy (HIE) in the intensive care unit (ICU). However, the sensitivity
      of standard clinical SEP recording techniques for detecting HFOs is unknown.
      METHODS: SEPs were recorded using routine clinical methods in 17 healthy subjects
      (median nerve stimulation; 0.5 ms pulse width; 5 Hz; maximum 4000 stimuli) in an
      unshielded laboratory. Bipolar EEG recordings were acquired (gain 50 k; bandpass
      3Hz-2 kHz; sampling rate 5 kHz; non-inverting electrode 2 cm anterior to C3/C4;
      inverting electrode 2 cm posterior to C3/C4). Data analysis was performed in
      MATLAB. RESULTS: SEP-HFOs were detected in 65% of controls using standard
      clinical recording techniques. In 3 controls without significant HFOs,
      experiments were repeated using a linear electrode array with higher spatial
      sampling frequency. SEP-HFOs were observed in all 3 subjects. CONCLUSIONS:
      Currently standard clinical methods of recording SEPs are not sufficiently
      sensitive to permit the inclusion of SEP-HFOs in routine clinical
      diagnostic/prognostic assessments. Whilst an increase in the number/density of
      EEG electrodes should improve the sensitivity for detecting SEP-HFOs, this
      requires confirmation. By improving and standardising clinical SEP recording
      protocols to permit the acquisition/analysis of SEP-HFOs, it should be possible
      to gain important insights into the pathophysiology of neurological disorders and
      refine the management of conditions such as HIE.

PMID- 29366908
TI  - A role for KCC3 in maintaining cell volume of peripheral nerve fibers.
AB  - The potassium chloride cotransporter, KCC3, is an electroneutral cotransporter
      expressed in the peripheral and central nervous system. KCC3 is responsible for
      the efflux of K+ and Cl- in neurons to help maintain cell volume and
      intracellular chloride levels. A loss-of-function (LOF) of KCC3 causes Hereditary
      Motor Sensory Neuropathy with Agenesis of the Corpus Callosum (HMSN/ACC) in a
      population of individuals in the Charlevoix/Lac-Saint-Jean region of Quebec,
      Canada. A variety of mouse models have been created to understand the
      physiological and deleterious effects of a KCC3 LOF. Though this KCC3 LOF in
      mouse models has recapitulated the peripheral neuropathy phenotype of HMSN/ACC,
      we still know little about the development of the disease pathophysiology.
      Interestingly, the most recent KCC3 mouse model that we created recapitulated a
      peripheral neuropathy-like phenotype originating from a KCC3 gain-of-function
      (GOF). Despite the past two decades of research in attempting to understand the
      role of KCC3 in disease, we still do not understand how dysfunction of this
      cotransporter can lead to the pathophysiology of peripheral neuropathy. This
      review focuses on the function of KCC3 in neurons and its role in human and
      health and disease.

PMID- 29366909
TI  - Hepatocyte-specific deletion of IL1-RI attenuates liver injury by blocking IL-1
      driven autoinflammation.
AB  - BACKGROUND & AIMS: Interleukin (IL)-1-type cytokines including IL-1alpha, IL
      1beta and interleukin-1 receptor antagonist (IL-1Ra) are among the most potent
      molecules of the innate immune system and exert biological activities through the
      ubiquitously expressed interleukin-1 receptor type 1 (IL-1R1). The role of IL-1R1
      in hepatocytes during acute liver failure (ALF) remains undetermined. METHODS:
      The role of IL-1R1 during ALF was investigated using a novel transgenic mouse
      model exhibiting deletion of all signaling-capable IL-1R isoforms in hepatocytes
      (Il1r1Hep-/-). RESULTS: ALF induced by D-galactosamine (D-GalN) and
      lipopolysaccharide (LPS) was significantly attenuated in Il1r1Hep-/- mice leading
      to reduced mortality. Conditional deletion of Il1r1 decreased activation of
      injurious c-Jun N-terminal kinases (JNK)/c-Jun signaling, activated nuclear
      factor-kappa B (NF-kappaB) p65, inhibited extracellular signal-regulated kinase
      (ERK) and prevented caspase 3-mediated apoptosis. Moreover, Il1r1Hep-/- mice
      exhibited reduced local and systemic inflammatory cytokine and chemokine levels,
      especially TNF-alpha, IL-1alpha/beta, IL-6, CC-chemokine ligand 2 (CCL2), C-X-C
      motif ligand 1 (CXCL-1) and CXCL-2, and a reduced neutrophil recruitment into the
      hepatic tissue in response to injury. NLRP3 inflammasome expression and caspase 1
      activation were suppressed in the absence of the hepatocellular IL-1R1.
      Inhibition of IL-1R1 using IL-1ra (anakinra) attenuated the severity of liver
      injury, while IL-1alpha administration exaggerated it. These effects were lost ex
      vivo and at later time points, supporting a role of IL-1R1 in inflammatory signal
      amplification during acute liver injury. CONCLUSION: IL-1R1 in hepatocytes plays
      a pivotal role in an IL-1-driven auto-amplification of cell death and
      inflammation in the onset of ALF. LAY SUMMARY: Acute liver injury which can cause
      lethal liver failure is medicated by a class of proteins called cytokines. Among
      these, interleukin-1 (IL-1) and the corresponding receptor IL-1R1 play a
      prominent role in the immune system, but their role in the liver is undetermined.
      In the current study, a novel mouse model with defective IL-1R1 in liver cells
      was studied. Mice lacking this receptor in liver cells were protected from cell
      death to a certain extent. This protection occurred only in the presence of
      other, neighboring cells, arguing for the involvement of proteins derived from
      these cells. This effect is called paracrine signaling and the current study has
      for the first time shown that the IL-1R1 receptor on hepatocytes is involved in
      acute liver failure in this context. The approved drug anakinra - which blocks IL
      1R1 - had the same effect, supporting the proposed mechanism of action. The
      findings of this study suggest new treatment options for patients with acute
      liver failure by blocking defined signals of the immune system.

PMID- 29366910
TI  - TGFbeta1-mediated suppression of cytochrome P450(CYP) induction responses in rat
      hepatocyte-fibroblast co-cultures.
AB  - Co-culture of hepatocyte and fibroblasts has shown distinct advantages in
      enhancing certain liver specific functions and maintaining hepatic polarity.
      However, the utility of hepatocyte co-culture models for studies, such as drug
      drug interaction studies, has not been completely elucidated. In this study the
      induction of Cyp1a2, Cyp2b1/2, and Cyp3a2, the three major cytochrome P450 (CYP)
      isoforms in the rat liver, was evaluated in randomly mixed co-cultures and
      micropatterned co-cultures. We found that in both co-culture configurations, the
      drug-induced Cyp1a2, Cyp2b1/2, Cyp3a2 mRNA and activity were suppressed relative
      to those in monocultured hepatocytes. Further, we observed a significant increase
      in TGFbeta1 production in the co-cultures. Addition of 100 pg/ml TGFbeta1 to
      hepatocyte monocultures resulted in the suppression of Cyp1a2, Cyp2b1/2, and
      Cyp3a2 induction. These findings implicate TGFbeta1 as one of the important
      factors impairing drug induced CYP induction in co-cultures and suggests that
      caution needs to be exercised in the use of hepatocyte-fibroblast co-cultures for
      CYP induction studies.

PMID- 29366912
TI  - Change in Physiological Variables in the Last Two Weeks of Life: An Observational
      Study of Hospitalized Adults With Heart Failure.
AB  - CONTEXT: Recognition of dying is a difficult task in end-stage heart failure, yet
      it remains an important clinical skill in providing good palliative care to these
      patients. OBJECTIVES: To use routinely collected data to explore evidence for
      physiological change in the final two weeks of life in end-stage heart failure.
      METHODS: This was a retrospective cohort study of routinely collected data from
      hospital inpatients dying as a result of heart failure during a one-year period
      in a U.K. hospital. Data were analyzed using descriptive techniques and
      multilevel modeling. RESULTS: Results were obtained on 81 patients. Respiratory
      function (evidenced by falling oxygen saturation and rising respiratory rate)
      deteriorated by a clinically significant amount in the final two weeks of life (P
      < 0.001). Renal function (evidenced by rising serum urea and creatinine) also
      demonstrated a clinically significant deterioration over the same period (P <
      0.001 and P = 0.005, respectively). Serum albumin fell over a period of months (P
      < 0.001). Heart rate and blood pressure did not demonstrate clinically
      significant change over the same period. CONCLUSIONS: Deteriorating respiratory
      and renal function may indicate imminent dying in heart failure. A fall in serum
      albumin may signify poor prognosis over a timescale of weeks to months.
      Conversely, hemodynamic parameters may remain relatively stable in the final days
      of life and should not be reassuring in end-stage heart failure patients.

PMID- 29366911
TI  - Coping Skills Practice and Symptom Change: A Secondary Analysis of a Pilot
      Telephone Symptom Management Intervention for Lung Cancer Patients and Their
      Family Caregivers.
AB  - CONTEXT: Little research has explored coping skills practice in relation to
      symptom outcomes in psychosocial interventions for cancer patients and their
      family caregivers. OBJECTIVES: To examine associations of coping skills practice
      to symptom change in a telephone symptom management (TSM) intervention delivered
      concurrently to lung cancer patients and their caregivers. METHODS: This study
      was a secondary analysis of a randomized pilot trial. Data were examined from
      patient-caregiver dyads (n = 51 dyads) that were randomized to the TSM
      intervention. Guided by social cognitive theory, TSM involved four weekly
      sessions where dyads were taught coping skills including a mindfulness exercise,
      guided imagery, pursed lips breathing, cognitive restructuring, problem solving,
      emotion-focused coping, and assertive communication. Symptoms were assessed,
      including patients' and caregivers' psychological distress and patients' pain
      interference, fatigue interference, and distress related to breathlessness.
      Multiple regression analyses examined associations of coping skills practice
      during the intervention to symptoms at six weeks after the intervention. RESULTS:
      For patients, greater practice of assertive communication was associated with
      less pain interference (beta = -0.45, P = 0.02) and psychological distress (beta
      = -0.36, P = 0.047); for caregivers, greater practice of guided imagery was
      associated with less psychological distress (beta = -0.30, P = 0.01).
      Unexpectedly, for patients, greater practice of a mindfulness exercise was
      associated with higher pain (beta = 0.47, P = 0.07) and fatigue interference
      (beta = 0.49, P = 0.04); greater practice of problem solving was associated with
      higher distress related to breathlessness (beta = 0.56, P = 0.01) and
      psychological distress (beta = 0.36, P = 0.08). CONCLUSION: Findings suggest that
      the effectiveness of TSM may have been reduced by competing effects of certain
      coping skills. Future interventions should consider focusing on assertive
      communication training for patients and guided imagery for caregivers.

PMID- 29366913
TI  - Culture and Palliative Care: Preferences, Communication, Meaning, and Mutual
      Decision Making.
AB  - Palliative care is gaining acceptance across the world. However, even when
      palliative care resources exist, both the delivery and distribution of services
      too often are neither equitably nor acceptably provided to diverse population
      groups. The goal of this study was to illustrate tensions in the delivery of
      palliative care for diverse patient populations to help clinicians to improve
      care for all. We begin by defining and differentiating culture, race, and
      ethnicity, so that these terms-often used interchangeably-are not conflated and
      are more effectively used in caring for diverse populations. We then present
      examples from an integrative literature review of recent research on culture and
      palliative care to illustrate both how and why varied responses to pain and
      suffering occur in different patterns, focusing on four areas of palliative care:
      the formation of care preferences, communication patterns, different meanings of
      suffering, and decision-making processes about care. For each area, we provide
      international and multiethnic examples of variations that emphasize the need for
      personalization of care and the avoidance of stereotyping beliefs and practices
      without considering individual circumstances and life histories. We conclude with
      recommendations for improving palliative care research and practice with cultural
      perspectives, emphasizing the need to work in partnerships with patients, their
      family members, and communities to identify and negotiate culturally meaningful
      care, promote quality of life, and ensure the highest quality palliative care for
      all, both domestically and internationally.

PMID- 29366914
TI  - The effects of a four week jump-training program on frontal plane projection
      angle in female gymnasts.
AB  - OBJECTIVES: To investigate the effects of a four week jump training program on
      frontal plane projection angle (FPPA) in young female gymnasts. DESIGN:
      Intervention study, consisting of a four week jump training program performed for
      15 min as part of a warm-up, three days per week for four weeks. SETTING:
      Gymnastics training center. PARTICIPANTS: Fourteen youth female gymnasts (age:
      13.5 +/- 2.14 years, height: 1.54 +/- 0.11 m, body mass: 46.23 +/- 7.68 kg). MAIN
      OUTCOME MEASURES: Change in FPPA during a 30 cm drop landing and tuck back
      somersault. RESULTS: Large and significant decreases (p < 0.001) in FPPA of 6.8
      degrees  (39%) and 8.4 degrees  (37%) during the drop landing and tuck back
      somersault, respectively. CONCLUSION: The jump training program was successful in
      improving FPPA in female gymnasts and is advised to be implemented into the warm
      ups and training programs of competitive female gymnasts to improve FPPA and
      therefore reduce the risk factors associated with knee injuries.

PMID- 29366915
TI  - Quantifying humeral retrotorsion in young swimmers and association with swim
      volume.
AB  - OBJECTIVES: To compare the humeral retrotorsion (HRT) among non-athletes, amateur
      swimmers and competitive swimmers and to analyze the relationship between HRT and
      swim volume in competitive swimmers. DESIGN: Cross-sectional. SETTING:
      Laboratory. PARTICIPANTS: Ninety children and adolescents, both genders (30 non
      athletes: 11.50 +/- 1.94 years; 30 amateur swimmers: 11.56 +/- 1.81 years; and 30
      competitive swimmers: 12.63 +/- 2.02 years). MAIN OUTCOME MEASURES: HRT
      measurement through the bicipital forearm angle (BFA), by palpation, using an
      inclinometer to obtain the angle. RESULTS: Competitive swimmers showed lower BFA
      (higher HRT) compared to the amateurs (mean difference: 8.3 degrees ; p = 0.013;
      effect size: 0.82) and to the non-athletes (mean difference: 8.5 degrees ; p =
      0.010; effect size: 0.80). A significant fair negative relationship (r = -0.37; p
      = 0.04) was found between BFA and volume of swim. CONCLUSION: Competitive young
      swimmers present increased HRT and a higher volume of swim is associated with a
      lower BFA (higher HRT) in these athletes. These results can help to improve the
      understanding of osseous adaptations in young swimmers.

PMID- 29366916
TI  - Employer attitudes towards general health checks and HIV testing in the
      workplace.
AB  - OBJECTIVE: There is a need to increase HIV testing rates in the UK. One approach
      is to increase access to testing through general health checks (GHCs) in the
      workplace. However, it is unclear whether GHCs are routinely offered by
      organisations, and employer perceptions of HIV testing are largely unknown. STUDY
      DESIGN: Online survey to assess attitudes towards and provision of general health
      checks and HIV testing in the workplace. METHODS: Ninety-eight employers from 25
      job sectors completed an online survey. Employers were 61 small and medium-sized
      enterprises (SME), 37 large organisations; 86% employing mobile workers, 77.6%
      employing migrant workers and 51.7% of employees were male workers. Items
      included employer attitudes around workplace health, GHC provision, content and
      delivery and attitudes towards workplace HIV testing including perceived benefits
      and barriers to HIV testing. RESULTS: Only one company offered opt-in workplace
      HIV testing. Seventy-eight companies (80%) did not provide any form of workplace
      GHC for employees. Decisions about health check provisions were not commonly
      informed by staff consultation (n = 6) or national guidelines (n = 4). Overall,
      100% of companies (n = 98) reported at least one benefit of HIV testing and 68
      (69%) believed that HIV testing should be offered in the workplace. Perceived
      barriers to HIV testing in the workplace were: [a] not having enough knowledge
      about HIV and testing; [b] not having trained staff to undertake HIV testing;
      and, [c] not knowing how to access HIV testing kits. Fifty-six companies (57.14%)
      would consider HIV testing as a future provision at their organisation. Sixty
      seven companies (68.37%) would like further guidance on workplace HIV testing.
      CONCLUSIONS: Few employers offer general health testing for employees, and opt-in
      HIV testing is exceptionally rare, despite positive attitudes towards it. There
      is a need to provide evidence-based guidance and support for employers around HIV
      testing in the workplace.

PMID- 29366917
TI  - Functional characterization of naturally occurring genetic variations of the
      human guanine-rich RNA sequence binding factor 1 (GRSF1).
AB  - The guanine-rich RNA sequence binding factor 1 (GRSF1) constitutes an
      ubiquitously occurring RNA-binding protein (RBP), which belongs to the family of
      heterogeneous nuclear ribonucleoprotein F/H (hnRNP F/H). It has been implicated
      in nuclear, cytosolic and mitochondrial RNA metabolism. Although the crystal
      structures of GRSF1 orthologs have not been solved, amino acid alignments with
      similar RNA-binding proteins suggested the existence of three RNA-binding domains
      designated quasi-RNA recognition motifs (qRRMs). Here we established 3D-models
      for the three qRRMs of human GRSF1 on the basis of the NMR structure of hnRNP F
      and identified the putative RNA interacting amino acids. Next, we explored the
      genetic variability of the three qRRMs of human GRSF1 by searching genomic
      databases and tested the functional consequences of naturally occurring mutants.
      For this purpose the RNA-binding capacity of wild-type and mutant recombinant
      GRSF1 protein species was assessed by quantitative RNA electrophoretic mobility
      shift assays. We found that some of the naturally occurring GRSF1 mutants
      exhibited a strongly reduced RNA-binding activity although the general protein
      structure was hardly affected. These data suggested that homozygous allele
      carriers of these particular mutants express dysfunctional GRSF1 and thus may
      show defective GRSF1 signaling.

PMID- 29366918
TI  - The Role of Rehabilitation in Patients With Progressive Supranuclear Palsy: A
      Narrative Review.
AB  - : Progressive supranuclear palsy (PSP) is a progressive neurodegenerative
      disorder caused by the deposition of abnormal proteins in neurons of the basal
      ganglia that limit motor ability, resulting in disability and reduced quality of
      life. So far, no pharmacologic therapy has been developed, and the treatment
      remains symptomatic. The aim of the present study is to perform a systematic
      investigation of the literature, and to determine the types and effects of
      rehabilitative interventions used for PSP. A search of all studies was conducted
      in MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials, CINAHL,
      and EMBASE. Twelve studies were identified, including 6 case reports, 3 case
      series, one case-control study, one quasi-randomized trial (i.e. not truly
      random) with crossover design, and one randomized controlled trial, with 88
      patients investigated overall. Rehabilitative interventions varied in type,
      number, frequency, and duration of sessions. The most commonly used clinical
      measures were the Progressive Supranuclear Palsy Rating Scale (PSPRS) and Unified
      Parkinson's Disease Rating Scale (UPDRS). Physical exercises were the main
      rehabilitative strategy but were associated with other interventions and
      rehabilitative devices, in particular treadmill and robot-assisted gait training.
      All studies showed an improvement in balance and gait impairment with a reduction
      of falls after rehabilitation treatment. Because of poor methodological quality
      and the variety of rehabilitative approaches including different and variable
      strategies, there was insufficient evidence of the effectiveness of any specific
      rehabilitation intervention in PSP. Despite this finding, rehabilitation might
      improve balance and gait, thereby reducing falls in PSP patients. LEVEL OF
      EVIDENCE: IV.

PMID- 29366919
TI  - Treatment of Postanoxic Action Myoclonus With Intrathecal Baclofen: A Case
      Report.
AB  - : A case of severe action myoclonus after pulmonary arrest is described. Although
      there was benefit from oral pharmacotherapy, action myoclonus remained disabling.
      A favorable response to baclofen during an intrathecal trial led to eventual
      placement of an intrathecal baclofen pump. The present case illustrates the
      potential utility of intrathecal baclofen for treating this condition. LEVEL OF
      EVIDENCE: V.

PMID- 29366920
TI  - Ca2+ levels in Daphnia hemolymph may explain occurrences of daphniid species
      along recent Ca gradients in Canadian soft-water lakes.
AB  - Calcium levels are declining in eastern North American and western European
      lakes. This widespread issue is affecting the composition of crustacean
      zooplankton communities, as the presence and abundance of several calcium-rich
      daphniid species are declining, while two other daphniids, D. catawba and D.
      ambigua, that apparently tolerate low calcium environments, are prospering. The
      physiological basis for low calcium tolerance of these daphniids is unknown. In
      this study the presence of one Ca-rich (D. pulicaria) and one Ca-poor (D.
      ambigua) daphniid species in Canadian Shield lakes is assessed in relation to
      lake water Ca levels. The occurrence of D. ambigua was independent of Ca levels
      in Ontario lakes, whereas D. pulicaria was more likely to occur in lakes with
      relatively more Ca. In the laboratory, D. ambigua maintained lower levels of
      hemolymph Ca2+ across a range of low Ca levels (0.7 to 7 mg l-1) compared with D.
      pulicaria. The hemolymph pH remained steady across this Ca gradient in D. ambigua
      while it was significantly more acidic in D. pulicaria in the two lowest Ca
      treatments. While Ca2+ uptake was observed adjacent to the surface of D. ambigua
      individuals, Ca2+ loss was observed for D. pulicaria assayed under moderately
      high Ca levels. Based on these observations we propose that D. ambigua is able to
      survive in low Ca lakes by maintaining low free ionic Ca2+ levels in the
      hemolymph which minimizes the Ca gradient across the body wall in low Ca water
      thus limiting overall Ca loss and facilitating Ca2+ uptake.

PMID- 29366921
TI  - Effects of the acclimation to high salinity on intestinal ion and peptide
      transporters in two tilapia species that differ in their salinity tolerance.
AB  - Tilapiine species, widely distributed across habitats with diverse water
      salinities, are important to aquaculture as well as a laboratory model. The
      effects of water salinity on two tilapia species, that differ in their salinity
      tolerance, was evaluated. Oreochromis niloticus reared in brackish-water, showed
      a significant decrease in growth and feed efficiency, whereas O. mossambicus
      reared in seawater did not show any significant changes. The expression and
      activity of Na+/K+-ATPase (NKA), V-type H+-ATPase (VHA) and carbonic anhydrase
      (CA), as well as expression levels of genes encoding two HCO3- and three peptide
      transporters (nbc1, slc26a6, slc15a1a, slc15a1b and slc15a2) were measured in
      three intestinal sections of these two species, grown in freshwater and
      brackish/sea-water. Overall, the spatial distribution along the intestine of the
      genes examined in this study was similar between the two species, with the
      exception of tcaIV. The salinity response, on the other hand, varied greatly
      between these species. In O. mossambicus, there was a salinity-dependent
      increased expression of most of the examined genes (except slc26a6 and slc15a2),
      while in O. niloticus the expression of most genes did not change, or even
      decreased (tcaIV, nbc1 and slc15a1b). This study highlighted differences in the
      intestinal response to salinity acclimation between closely- related species that
      differ in their salinity tolerance. O. mossambicus, which has a high salinity
      tolerance, showed expression patterns and responses similar to marine species,
      and differed from the low-salinity-tolerance O. niloticus, which showed a
      response that differed from the accepted models, that are based on marine and
      diadromous fishes.

PMID- 29366922
TI  - Motor skills intervention research of children with disabilities.
AB  - BACKGROUND: Physical inactivity and obesity among children with physical and
      cognitive disabilities is an emerging public health issue. Children's motor skill
      development is a determinant of lifelong physical activity and obesity. AIMS: The
      purpose of this article is to critically evaluate motor skill intervention
      literature among children with physical and cognitive disabilities. METHODS AND
      PROCEDURES: Electronic searches were completed to identity research articles
      published from 1984 to 2014. Major findings were categorized among subtopics
      including characteristics of intervention studies, research designs, diagnostic
      method, motor skill interventions and motor skill outcome. OUTCOMES AND RESULTS:
      21 studies were found and included participants with developmental delay (42.8%),
      autism (19.0%), cross-disability (19.0%), intellectual disability (4.8%),
      cerebral palsy (4.8%), developmental coordination disorder (4.8%), and learning
      disabilities (4.8%). Only one study was a randomized controlled trial.
      CONCLUSIONS: and implications: The current literature on motor skill intervention
      research is broad in scope and has limited generalizability within and across
      disability groups. Future research is needed to develop cross-disability
      intervention methods adaptable to disability and function-specific needs,
      including the utilization of rapidly developing technology. Researchers are
      encouraged to utilize sound methodology with robust theoretical foundations.
      Family and community engagement is encouraged in intervention delivery.

PMID- 29366923
TI  - Handwriting difficulties in children with attention deficit hyperactivity
      disorder (ADHD).
AB  - Handwriting is fundamental in school and everyday life situations. Legibility
      guarantees that writing productions communicate information, and speed is often
      crucial, especially in children with attention deficit and hyperactivity disorder
      (ADHD), in order to increase the likelihood of their being able to work
      efficiently and stay on-task during school activities. Preliminary reports have
      shown an impairment in handwriting of children with ADHD, but evidence is still
      unclear, especially in the case of speed where research has offered contradictory
      results. Children's performance, furthermore, has yet to be investigated under
      the cognitive loading conditions typical of academic tasks in classroom. To shed
      light on this matter, we examined the handwriting performance in a simple
      condition but also under (verbal or spatial) working memory (WM) load in 16
      fourth- and fifth-grade children with symptoms of ADHD and 16 matched control
      children. Our results showed that the groups speed differed significantly only in
      the verbal WM loading condition, where children with symptoms of ADHD wrote more
      slowly and showed a greater intra-individual variability than controls.
      Handwriting legibility was affected by verbal WM loading too. These findings are
      discussed in relation to their educational and clinical implications.

PMID- 29366924
TI  - Examination of gait parameters during perturbed over-ground walking in children
      with autism spectrum disorder.
AB  - BACKGROUND: Many children with Autism Spectrum Disorder (ASD) are school-aged and
      typically carry a backpack. It is important to understand how this task affects
      walking. Weighted vests (WVs) often prescribed to mitigate behavioral effects of
      ASD. The effects of backpack and WV walking have not been examined in children
      with ASD. AIMS: To quantify differences in lower extremity mechanics in children
      with ASD during WV and backpack walking. METHODS: Eight male participants
      completed 15 trials in three conditions: body mass, and carrying or wearing a
      backpack or WV with 15% added body mass. Three-dimensional kinematic data were
      collected and normalized to 100% of the gait cycle. The Model Statistic was
      utilized to test for bilateral asymmetries between the lower extremity joints at
      all points along the gait cycle. RESULTS: Analysis revealed similar numbers of
      significant asymmetries in hip (71.0, 70.4, 60.6), knee (68.4, 71.5, 74.6), and
      ankle (64.1, 68.9, 68.4) for unloaded, backpack, and WV, respectively.
      CONCLUSION: Participants exhibited individualized kinematic symmetry-responses to
      the loaded conditions compared to the unloaded condition. These findings suggest
      that 15% body mass backpack or WV does not affect gait symmetry in children with
      ASD.

PMID- 29366925
TI  - Pharmacological intervention in hypertension using beta-blockers: Real-world
      evidence for long-term effectiveness.
AB  - The study objective was to compare the long-term incidence and risk of mortality
      and cardiovascular outcomes in patients with hypertension initiating bisoprolol,
      other beta-blockers or other antihypertensive therapies. Cohort analysis using UK
      Clinical Practice Research Datalink (CPRD). Adult patients with first diagnosis
      of hypertension recorded between 2000 and 2014, with >=365 days of registration
      to first event and initiating monotherapies of bisoprolol, other beta-blockers or
      drugs other than beta-blockers within 6 months of diagnosis were included.
      Incidence rates (IR) for each treatment cohort were compared using adjusted
      hazard ratio (HR) and 95% confidence intervals (CI) obtained from Cox regression
      analyses. Of 100,066 patients included, 539 were prescribed bisoprolol, 3701
      other beta-blockers, and 95,826 drugs other than beta-blockers. Patients
      receiving bisoprolol had significantly increased survival from 2 up to <15 years
      (HR for <15 years 0.34; 95% CI 0.18-0.67) versus other beta-blockers, and from 5
      to <15 years (HR for <15 years 0.52; 95% CI 0.27-1.00) versus drugs other than
      beta-blockers. Over time, the risk of arrhythmia was higher in the bisoprolol
      cohort versus other beta-blockers, and risks of arrhythmia and angina were higher
      versus drugs other than beta-blockers. No differences in the risk of embolism,
      stroke, and myocardial infarction (MI) were found between cohorts. Over time,
      mortality and cardiovascular outcome IRs decreased in each cohort. In conclusion,
      bisoprolol showed sustained benefit on survival, evident from 2 years after
      treatment initiation versus other beta-blockers, and from 5 years versus drugs
      other than beta-blockers, providing long-term evidence supporting the use of
      bisoprolol in patients with hypertension in primary care.

PMID- 29366926
TI  - Intermolecular interaction and solid state characterization of abietic
      acid/chitosan solid dispersions possessing antimicrobial and antioxidant
      properties.
AB  - The aim of this work was to prepare and characterize solid dispersions of abietic
      acid (AB) and chitosan (CS) to investigate how formulation of the mixture may
      help in the battle against microbial colonization in different areas, such as the
      biomedical field or the food industry. Solid dispersions were characterized by
      differential scanning calorimetry, infrared spectroscopy, Raman spectroscopy,
      polarized optical microscopy, zeta potential and size analysis. The data showed
      that the dispersion/solvent evaporation method formed solid dispersions in which
      abietic acid was molecularly dispersed in the carrier. A synergistic effect
      between the two components in terms of antioxidant and antimicrobial properties
      was found, especially in the formulations obtained with 1/1 AB/CS molar ratio.
      Interestingly, the aggregation state (amorphous/crystalline) of AB seemed to
      affect the antimicrobial activity of the formulation, suggesting increased
      bioactivity when the drug was in the amorphous state. These findings, together
      with the demonstrated biocompatibility of the formulations, seem to open
      promising perspectives for a successful application of the developed AB/CS
      formulations in the biomedical field or in the food industry.

PMID- 29366927
TI  - Eosinophilic Gastroenteritis Presenting With Gastric Perforation.

PMID- 29366928
TI  - F-FDG-PET and Celiac Disease.

PMID- 29366929
TI  - Segmental Xanthomatosis of the Ileum.

PMID- 29366930
TI  - Sustained reversal of central neuropathic pain induced by a single intrathecal
      injection of adenosine A2A receptor agonists.
AB  - Central neuropathic pain is a debilitating outcome of spinal cord injury (SCI)
      and current treatments to alleviate this pain condition are ineffective. A
      growing body of literature suggests that activating adenosine A2A receptors
      (A2ARs) decreases the production of proinflammatory cytokines and increases the
      production of anti-inflammatory cytokines. Here, the effect of administering
      intrathecal A2AR agonists on central neuropathic pain was measured using hindpaw
      mechanical allodynia in a rat model of SCI termed spinal neuropathic avulsion
      pain (SNAP). Other models of SCI cause extensive damage to the spinal cord,
      resulting in paralysis and health problems. SNAP rats with unilateral low
      thoracic (T13)/high lumbar (L1) dorsal root avulsion develop below-level
      bilateral allodynia, without concomitant motor or health problems. A single
      intrathecal injection of the A2AR agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N
      ethylcarboxamido adenosine HCl (CGS21680) reversed SCI-induced allodynia for at
      least 6 weeks. The reversal is likely in part mediated by interleukin (IL)-10, as
      intrathecally administering neutralizing IL-10 antibodies 1 week after CGS21680
      abolished the anti-allodynic effect of CGS21680. Dorsal spinal cord tissue from
      the ipsilateral site of SCI (T13/L1) was assayed 1 and 6 weeks after CGS21680 for
      IL-10, CD11b, and tumor necrosis factor (TNF) gene expression. CGS21680 treatment
      did not change IL-10 gene expression but did significantly decrease CD11b and TNF
      gene expression at both timepoints. A second A2AR agonist, 4-(3-(6-amino-9-(5
      cyclopropylcarbamoyl-3,4-dihydroxytetrahydrofuran-2-yl)-9H-purin-2-yl)prop-2
      ynyl)piperidine-1-carboxylic acid methyl ester (ATL313), was also able to
      significantly prevent and reverse SCI-induced allodynia for several weeks after a
      single intrathecal injection, providing converging lines of evidence of A2AR
      involvement. The enduring pain reversal after a single intrathecal injection of
      A2AR agonists suggests that A2AR agonists could be exciting new candidates for
      treating SCI-induced central neuropathic pain.

PMID- 29366931
TI  - In vitro antiplasmodial efficacy of synthetic coumarin-triazole analogs.
AB  - Twenty two diverse coumarin-triazole derivatives were synthesized by alkylation
      of 7-hydroxy-4-methyl-coumarin followed by click chemistry at 7-position. These
      compounds were evaluated for their in vitro antiplasmodial activity against
      chloroquine sensitive strain of Plasmodium falciparum (3D7). Compound 9 (7-[1-(2,
      4-dimethoxy-phenyl)-1H- [1-3] triazol-4-ylmethoxy]-4-methyl-chromen-2-one) was
      found most active with IC50 value 0.763 +/- 0.0124 MUg/mL. Further, the structure
      of compound 20 was characterized by single crystal X-ray diffraction. In view of
      impressive results, we considered it worthwhile to validate the results of in
      vitro antiplasmodial activity by assessing whether these compounds are capable of
      hampering the catalytic activity of DNA gyrase, thus preventing its supercoiling
      function.

PMID- 29366933
TI  - Similar taste-nutrient relationships in commonly consumed Dutch and Malaysian
      foods.
AB  - Three recent studies showed that taste intensity signals nutrient content.
      However, current data reflects only the food patterns in Western societies. No
      study has yet been performed in Asian culture. The Malaysian cuisine represents a
      mixture of Malay, Chinese and Indian foods. This study aimed to investigate the
      associations between taste intensity and nutrient content in commonly consumed
      Dutch (NL) and Malaysian (MY) foods. Perceived intensities of sweetness,
      sourness, bitterness, umami, saltiness and fat sensation were assessed for 469
      Dutch and 423 Malaysian commonly consumed foods representing about 83% and 88% of
      an individual's average daily energy intake in each respective country. We used a
      trained Dutch (n = 15) and Malaysian panel (n = 20) with quantitative sensory
      SpectrumTM 100-point rating scales and reference solutions, R1 (13-point), R2 (33
      point) and R3 (67-point). Dutch and Malaysian foods had relatively low mean
      sourness and bitterness (<R1), but higher mean sweetness, saltiness and fat
      sensation (between R1 and R2). Mean umami taste intensity of Malaysian foods (15
      point) was higher than that of Dutch foods (8-point). Positive associations were
      found between sweetness and mono- and disaccharides (R2 = 0.67 (NL), 0.38 (MY)),
      between umami and protein (R2 = 0.29 (NL), 0.26 (MY)), between saltiness and
      sodium (R2 = 0.48 (NL), 0.27 (MY)), and between fat sensation and fat content (R2
      = 0.56 (NL), 0.17(MY)) in Dutch and Malaysian foods (all, p < 0.001). The
      associations between taste intensity and nutrient content are not different
      between different countries, except for fat sensation-fat content. The two
      dimensional basic taste-nutrient space, representing the variance and
      associations between tastes and nutrients, is similar between Dutch and Malaysian
      commonly consumed foods.

PMID- 29366934
TI  - Sodium thiosulfate mediated cardioprotection against myocardial ischemia
      reperfusion injury is defunct in rat heart with co-morbidity of vascular
      calcification.
AB  - Sodium thiosulfate (STS) has shown promising effects in amelioration of
      myocardial ischemia-reperfusion injury (IR) in a rat model and is clinically
      useful in the treatment of chronic kidney disease (CKD) associated calciphylaxis.
      As the prevalence of cardiac complications is higher in CKD, we tested the
      effectiveness of STS in a rat model of adenine-induced vascular calcification and
      subjected the heart to IR. We observed an increased infarct size (29%) by TTC
      staining, lactate dehydrogenase (54%) and creatine kinase (32%) release in the
      coronary perfusate and altered hemodynamics compared to a normal rat treated with
      STS and subjected to IR. As functional mitochondria are essential for preserving
      heart from the detrimental effects of IR, we found that calcification induced
      mitochondrial dysfunction (reduced RCR->80%, P/O ratio->30%, DeltaPsi->10% and
      swelling- 27%), could not be restored efficiently by STS treatment. Therefore we
      used nicorandil (mitochondrial potassium channel opener) along with STS as a
      combination therapy to treat the diseased heart and found an improvement in
      cardioprotection against IR injury, compared to STS alone. Upon evaluating these
      hearts, we found that both the cardiac mitochondria namely interfibrillar and
      subsarcolemmal were functionally well preserved.

PMID- 29366935
TI  - Glycine betaine rather than acting only as an osmolyte also plays a role as
      regulator in cellular metabolism.
AB  - For many years, glycine betaine (GB) has been widely studied as an osmolyte in
      plants and bacteria. In animal cells, GB is an osmolyte mainly in the kidneys,
      but in humans many studies have shown its role as a methyl donor in homocysteine
      metabolism in the liver. GB is also a protein stabilizer, and thus, it became
      known as an osmoprotector. In many organisms GB is synthesized from choline and
      can also be obtained from some foods. Over the last twenty years GB has gone from
      being considered simply as an osmolyte to being known as a cytoprotector involved
      in cell metabolism and as a chemical chaperone. The aim of this review was to
      gather information about the role of GB in the metabolism of ethanol, lipids,
      carbohydrates and proteins in animals. The information generated thus far shows
      that GB regulates enzymes involved in the homocysteine/methionine cycle, sucrose,
      glucose, fructose and glycogen metabolism, in oxidative and ER-stress caused by
      ethanol abuse, likewise enzymes involved in lipogenesis and fatty oxidation.
      Besides, there are data supporting that GB regulates the transcription factors
      PPARalpha, NF-kappaB, FOX1, ChREBP and SREBP1 and this lets GB play a role in
      protein synthesis. One of the main mechanisms by which GB regulates the enzymes
      is by changes in their activity either because GB increases their expression or
      because it regulates changes in their phosphorylation status through specific
      kinases. GB modulates the expression of genes by changing the degree of
      methylation in the promoter of target genes. The exact mechanism by which GB
      modifies the methylation status of the promoter is not yet clear, but methyl
      transferases that use SAM as methyl donor and DNA methyl transferases are good
      candidates for this function.

PMID- 29366932
TI  - A systematic review of attentional biases in disorders involving binge eating.
AB  - OBJECTIVE: Attentional bias (AB) may be one mechanism contributing to the
      development and/or maintenance of disordered eating. AB has traditionally been
      measured using reaction time in response to a stimulus. Novel methods for AB
      measurement include eye tracking to measure visual fixation on a stimulus, and
      electroencephalography to measure brain activation in response to a stimulus.
      This systematic review summarizes, critiques, and integrates data on AB gathered
      using the above-mentioned methods in those with binge eating behaviors, including
      binge eating, loss of control eating, and bulimia nervosa. METHOD: Literature
      searches on PubMed and PsycInfo were conducted using combinations of terms
      related to binge eating and biobehavioral AB paradigms. Studies using AB
      paradigms with three categories of stimuli were included: food, weight/shape, and
      threat. For studies reporting means and standard deviations of group bias scores,
      Hedges' g effect sizes for group differences in AB were calculated. RESULTS:
      Fifty articles met inclusion criteria and were reviewed. Individuals who binge
      eat in the absence of compensatory behaviors show an increased AB to food cues,
      but few studies have examined such individuals' AB toward weight/shape and
      threatening stimuli. Individuals with bulimia nervosa consistently show an
      increased AB to shape/weight cues and socially threatening stimuli, but findings
      for AB to food cues are mixed. DISCUSSION: While there are important research
      gaps, preliminary evidence suggests that the combination of AB to disorder
      specific cues (i.e., food and weight/shape) and AB toward threat may be a potent
      contributor to binge eating. This conclusion underscores previous findings on the
      interaction between negative affect and AB to disorder-specific cues.
      Recommendations for future research are provided.

PMID- 29366936
TI  - Functional attribution of LdISP, an endogenous serine protease inhibitor from
      Leishmania donovani in promoting infection.
AB  - Leishmaniasis, a parasitic disease caused by unicellular eukaryotic protozoa of
      the genus Leishmania, affects more than 12 million people worldwide. Events of
      leishmaniasis are based on the infection of the mammalian host, precisely
      macrophages, where both host and parasite derived proteases and endogenous
      inhibitors are significant. Pathogen derived protease inhibitors have generated
      considerable interest as they often act as an agent promoting infection and
      parasitic survivability. An endogenous serine protease inhibitor from Indian
      strain of Leishmania donovani was previously identified by our group and named as
      LdISP. It has been found to inhibit neutrophil elastase (NE), responsible for
      natural inflammation process. However, LdISP's role in progression of infection
      or the proteomics based structural exposition has not been explored. The present
      study is aimed to localize and validate the potential role of LdISP in
      infectivity. We found that LdISP localized endogenously and treatment of infected
      host cells with LdISP curbs ROS and NO production. Additionally, in silico
      studies are carried out to predict the putative amino acid residues of LdISP
      involved in the inhibition process. Taken together, our results demonstrate that
      LdISP eventually exerts a pronounced role in L. donovani infection.

PMID- 29366937
TI  - Designer microbiomes for environmental, energy and health biotechnology.
AB  - Biotechnology conventionally uses pure strains of microorganisms to realize a
      desired conversion. The design of functional microbiomes is becoming a powerful
      alternative for when an aseptic environment is not an option, either for economic
      reasons or if the environment is intrinsically open. Rapid technological
      developments in combined -omics approaches is enabling the engineering and
      optimization of highly complex microbiomes. This review outlines emerging
      principles of design and provides examples of successful approaches and
      interventions in wastewater treatment, bioenergy production and the human
      intestinal microbiome.

PMID- 29366938
TI  - A compact, portable, re-configurable, and automated system for on-demand
      pharmaceutical tablet manufacturing.
AB  - Due to the complex nature of the pharmaceutical supply chain, the industry faces
      several major challenges when it comes to ensuring an adequate supply of quality
      drug products. These challenges are not only the causes of supply chain
      disruptions and financial loss, but can also prevent underserved and remote areas
      from receiving life-saving drugs. As a preliminary demonstration to mitigate all
      these challenges, at MIT we have developed active pharmaceutical ingredients
      manufacturing in a miniature platform. However, manufacturing of final oral solid
      dosage as tablets from drug substances had not been demonstrated. In this study,
      a compact, portable, re-configurable, and automated tablet manufacturing system,
      roughly the size of a North American household oven, [72.4 cm (length) * 53.3 cm
      (width) * 134.6 cm (height)] was designed, built and demonstrated. This miniature
      system is able to manufacture on-demand tablets from drug crystals on a scale of
      hundreds to thousands per day. Ibuprofen and Diazepam, each having different drug
      loading, were manufactured using this miniature system and meet U.S. Pharmacopeia
      standards. We foresee this flexible, miniature, plug-and-play pharmaceutical
      solids dosage manufacturing system advancing on-demand ready-to-use
      pharmaceuticals enabling future treatment of human diseases at the point-of-care.

PMID- 29366939
TI  - Statistical Design of Experiment (DoE) based development and optimization of
      DB213 in situ thermosensitive gel for intranasal delivery.
AB  - DB213 is an HIV-1 replication inhibitor targeting the Central Nervous System for
      the treatment of HIV-associated neurocognitive disorders. Current study aims to
      develop an in situ thermosensitive gelling system for intranasal delivery of
      DB213 facilitated by Statistical Design of Experiment (DoE) to conduct a more
      efficient experimentation by extracting the maximum amount of information from
      limited experiments. In our current study, information was extracted from twenty
      five experimental designs from MODDE(r) Software and a mathematical model was
      successfully developed to predict formulations to achieve desired performance as
      well as to analyze relationships between the amount of Pluronic F-127, Pluronic F
      68, Chitosan, DB213 and the performances of in situ thermosensitive gels. Based
      on DoE, in situ thermosensitive gels of 1% DB213 (F1) and 5% DB213 (F2) were
      developed for further in vivo bioavailability and brain uptake evaluations in
      Sprague-Dawley rats and C57BL/6 mice, respectively. In comparison to DB213 water
      solution, intranasal administrations of F1 at 1 mg/kg in rats and F2 at 25 mg/kg
      in mice demonstrated relative bioavailabilities of 145% and 165% with significant
      increase in brain uptake.

PMID- 29366940
TI  - Evaluation of toxicity of glycerol monooleate nanoparticles on PC12 cell line.
AB  - An innovative approach to improve drug delivery is the use of glycerol monooleate
      nanoparticles. Numerous studies describe their high versatility, low toxicity and
      ability to carry relatively high loads of conjugated compounds including scarcely
      soluble ones, providing sustained drug release and increasing drug diffusion and
      half-life. Despite a growing interest in their potential use for therapeutic
      applications, there are surprisingly few literature data concerning the toxic
      effects of these nanoparticles at high concentrations in vitro and in vivo, and
      their effects on cell metabolism. We produced and characterized from a physical
      chemical point of view glycerol monooleate nanoparticles and tested them on the
      PC12 cell line, a rat model of neuronal differentiation. The toxicity of these
      nanoparticles was evaluated by molecular methods on cell viability, cell cycle,
      nanoparticle uptake and induction of apoptosis. The results showed that glycerol
      monooleate nanoparticles up to 100 MUg/mL had no toxic effects on PC12 cells, did
      not induce significant changes in the cell cycle nor cause apoptosis. The
      nanoparticles entered PC12 cells 8 h after treatment, successfully delivering the
      conjugate compound inside cells. Overall, glycerol monooleate nanoparticles did
      not exhibit significant toxicity on PC12 cell line in concentrations up to 100
      ug/mL, supporting their therapeutic use as drug delivery systems.

PMID- 29366941
TI  - Inorganic nanoparticles: A potential cancer therapy for human welfare.
AB  - Cancer is an abnormal condition leading to uncontrolled cell division which
      causes damage to the body tissues. Around 100 types of cancer are studied so far
      namely breast cancer, lung cancer, skin cancer, prostate cancer, colon cancer and
      lymphoma. Major cancer therapies include chemotherapy, surgery and radiations but
      their major drawbacks are non-specifically distributed antitumor agents, uneven
      delivery of drug concentration to the tumour and low monitoring. Nanoparticles
      (NPs) are the newly trending field of nanomedicine implied in cancer therapy. The
      structural characteristics of NPs makes them excellent mode for targeting and
      penetrating the abnormal cell growth caused by cancer. They can potentially enter
      the abnormal cells causing DNA damage and determine the defects in the genes.
      Apart from targeting cancer cells they also aid in drug delivery, imaging of
      abnormal cells, release and monitoring of therapeutic agents against cancer. The
      present review deals with the inorganic NPs mediated pharmacotherapy, potential
      strategies for developing drug delivery system, evaluate the merits and demerits
      of traditional chemotherapy and nanotherapy for significantly improving the
      treatment of cancers.

PMID- 29366942
TI  - Optimization of a semi-batch tablet coating process for a continuous
      manufacturing line by design of experiments.
AB  - The aim of the study was to optimize a tablet coating process for a continuous
      manufacturing line. High throughputs should be achieved while inter-tablet
      coating variability should be as small as possible. Drug-free cores were coated
      with a colored suspension. All processes were monitored in-line with Raman
      spectroscopy. A statistical design of experiment was performed to find optimum
      process parameters. Tablet loading, spray rate and drum rotation speed were
      studied. Image analysis was performed using a computer scanner. Tablet hue and
      saturation were evaluated to obtain information about the inter-tablet color
      variabilities and the numbers of outliers. Low variabilities could be achieved
      using low spray rates and high rotation speeds and they were independent from the
      tablet batch sizes in the studied factor space. For the prediction of the coating
      thickness, univariate analysis was compared to PLS-regression. Calibration models
      were built based on the three center points of the statistical design of
      experiment resulting in RMSEC of 1.07% of sprayed suspension with R2 of 0.9989
      and Q2 of 0.9987. Model prediction was possible independent from loading, spray
      rate and drum rotation speed. The experiment with lowest color variability was
      conducted with a desired throughput rate of 25 kg/h and with a RMSEP of 2.5%.

PMID- 29366943
TI  - Membrane properties for permeability testing: Skin versus synthetic membranes.
AB  - Synthetic membranes that are utilized in diffusion studies for topical and
      transdermal formulations are usually porous thin polymeric sheets for example
      cellulose acetate (CA) and polysulfones. In this study, the permeability of human
      skin was compared using two synthetic membranes: cellulose acetate and Strat-M(r)
      membrane and lipophilic and hydrophilic compounds either as saturated or
      formulated solutions as well as marketed dosage forms. Our data suggests that
      hydrophilic compounds have higher permeation in Strat-M membranes compared with
      lipophilic ones. High variation in permeability values, a typical property of
      biological membranes, was not observed with Strat-M. In addition, the
      permeability of Strat-M was closer to that of human skin than that of cellulose
      acetate (CA > Strat-M > Human skin). Our results suggest that Strat-M with little
      or no lot to lot variability can be applied in pilot studies of diffusion tests
      instead of human skin and is a better substitute than a cellulose acetate.

PMID- 29366944
TI  - 3D printing of vaginal rings with personalized shapes for controlled release of
      progesterone.
AB  - Vaginal rings are gynecological drug delivery devices with fixed shapes, sizes
      and drug doses. Here 3D printed personalized progesterone-loaded vaginal rings
      were prepared. Progesterone was mixed with polyethylene glycol (PEG) 4000 to form
      a solid dispersion that was cut into pieces. The mixture of poly(lactic acid)
      (PLA)/polycaprolactone (PCL) (8:2) and Tween 80 were mixed with the above pieces
      and hot-melted to form filaments. A fused deposition modeling (FDM) printer was
      used to prepare "O", "Y" or "M"-shaped vaginal rings with the filaments.
      Differential scanning calorimetry and X-ray powder diffraction showed that
      amorphous progesterone existed in the rings. Moreover, progesterone did not
      decompose in the preparation according to the thermal gravimetric analysis.
      Surface pores and inner channels appeared in the rings due to PEG 4000
      dissolution and Tween 80 made the rings wettable. The "O" ring had higher
      dissolution than the "Y" and "M" rings due to its higher surface area/volume
      ratio and special shape. The vaginal rings showed the long-term sustained release
      of progesterone for more than 7 days with diffusion-controlled release behavior.
      The 3D printed vaginal rings are promising local gynecological medications. 3D
      printing is an effective strategy for preparation of personalized and customized
      medications.

PMID- 29366945
TI  - The relevance of shear, sedimentation and diffusion during spin freezing, as
      potential first step of a continuous freeze-drying process for unit doses.
AB  - Recently, a continuous freeze-drying process for the production of unit doses was
      presented and evaluated. In this concept, the freezing step is modified compared
      to traditional batch freeze-drying, as glass vials filled with a liquid
      formulation, are rotated around their longitudinal axis while cooled and frozen
      with a cold, sterile and inert gas (i.e. spin freezing). Finally, a thin frozen
      product layer spread over the entire vial wall is achieved. The aim of this paper
      is twofold: firstly, the relation between the rotation velocity and the relative
      difference between top and bottom of the frozen product layer thickness was
      determined for different vial types. Secondly, the impact of shear and
      centrifugal forces generated during spinning was examined, to find out whether
      they might cause pharmaceutical instability and sedimentation, respectively.
      Mechanistic and experimental evaluation showed that shear has no effect on
      proteins. Calculations showed that the sedimentation and diffusion velocity is
      too low to cause inhomogeneity in the product layer. In addition, Global
      Sensitivity Analysis (GSA) and Uncertainty Analysis (UA) were performed in order
      to account for the uncertainty of the used mechanistic model.

PMID- 29366946
TI  - Mechanochemical effect on swelling and drug release of natural polymer matrix
      tablets by X-ray computed tomography.
AB  - The relationships between the physicochemical properties of milled starch and
      drug release from tablets were investigated quantitatively using a drug release
      kinetic method and X-ray computed tomography (XCT). The samples were prepared
      from raw beta-starch by milling in a planetary ball mill. The tablets, containing
      5% theophylline (TH), 94% milled starch, and 1% magnesium stearate, were
      compressed at 6 kN. The drug-release and gel-forming processes were measured
      simultaneously using an original dissolution tester with an XCT instrument. Drug
      release from the tablet was delayed with increasing milling time, because the TH
      tablet formed a typical gel-layer on the outside of the tablet. The relationship
      between the crystallinity of milled starch and mean drug release time (MDT) for
      the TH tablets showed almost a straight inverse proportional relationship. The
      plots of MDT against area under the curve of the swelling ratio profiles of the
      TH tablets had a good straight line.

PMID- 29366947
TI  - Quantification of DNA damage products by gas chromatography tandem mass
      spectrometry in lung cell lines and prevention effect of thyme antioxidants on
      oxidative induced DNA damage.
AB  - Lung cancer has a high treatment cost and poor prognosis in comparison to other
      types of cancers. This work was involved in studying oxidative DNA base damage
      inhibition. Accordingly, standard carvacrol, thymol, thymoquinone with water and
      water-methanol extract of thyme (Origanum vulgare L. subsp. hirtum (link.)
      Ietswaart), thyme oil and thyme water were prepared and investigated for their
      efficacy to inhibit DNA oxidative damage formed by H2O2 in malignant lung cells
      (A549). The antioxidant capacity by ABTS assay was 271.73 +/- 11.45 mg trolox
      equivalent/mL for thyme oil. HPLC analysis was carried out to determine the
      contents of different thyme extracts, results showing the presence of carvacrol,
      thymol, protocatechuic acid, caffeic acid, epicatechin and rosmarinic acid in
      water and water-methanol extracts while only carvacrol and thymol were found in
      thyme oil and thyme water. After DNA isolation from the cultured cells, the
      formed oxidative induced DNA damage products were analysed using GC-MS/MS. It was
      proven that the antioxidants in the cell culture media have succeeded to inhibit
      oxidative DNA base damage. Thymoquinone was shown to be the best protectant
      antioxidant among other antioxidants against the formation of oxidative DNA
      damage, whereas water-methanol extract of thyme was the best among the plant
      sourced samples. Thymoquinone and thyme water-methanol extract were investigated
      for their efficacy on cultured healthy lung cells (BEAS-2B), and it was proven
      that they are efficient in protection against the oxidation of DNA of healthy
      lung cells too.

PMID- 29366948
TI  - Neural representations for newly learned words are modulated by overnight
      consolidation, reading skill, and age.
AB  - Word learning depends not only on efficient online binding of phonological,
      orthographic and lexical information, but also on consolidation of new word
      representations into permanent lexical memory. Work on word learning under a
      variety of contexts indicates that reading and language skill impact facility of
      word learning in both print and speech. In addition, recent research finds that
      individuals with language impairments show deficits in both initial word form
      learning and in maintaining newly learned representations over time, implicating
      mechanisms associated with maintenance that may be driven by deficits in
      overnight consolidation. Although several recent studies have explored the neural
      bases of overnight consolidation of newly learned words, no extant work has
      examined individual differences in overnight consolidation at the neural level.
      The current study addresses this gap in the literature by investigating how
      individual differences in reading and language skills modulate patterns of neural
      activation associated with newly learned words following a period of overnight
      consolidation. Specifically, a community sample of adolescents and young adults
      with significant variability in reading and oral language (vocabulary) ability
      were trained on two spoken artificial lexicons, one in the evening on the day
      before fMRI scanning and one in the morning just prior to scanning. Comparisons
      of activation between words that were trained and consolidated vs. those that
      were trained but not consolidated revealed increased cortical activation in a
      number of language associated and memory associated regions. In addition,
      individual differences in age, reading skill and vocabulary modulated learning
      rate in our artificial lexicon learning task and the size of the cortical
      consolidation effect in the precuneus/posterior cingulate, such that older
      readers and more skilled readers had larger cortical consolidation effects in
      this learning-critical region. These findings suggest that age (even into late
      adolescence) and reading and language skills are important individual differences
      that affect overnight consolidation of newly learned words. These findings have
      significant implications for understanding reading and language disorders and
      should inform pedagogical models.

PMID- 29366949
TI  - Impaired theory of mind in adults with traumatic brain injury: A replication and
      extension of findings.
AB  - OBJECTIVE: To replicate a previous study of Theory of Mind (ToM) task performance
      in adults with traumatic brain injury (TBI) under different working memory (WM)
      demands, and determine if there are sex-based differences in effects of WM load
      on ToM task performance. METHOD: 58 adults with moderate-severe TBI (24 females)
      and 66 uninjured adults (34 females) matched group-wise for age, sex, and
      education viewed a series of video vignettes from the Video Social Inference Task
      (VSIT) (Turkstra, 2008) and answered ToM questions. Vignette presentation format
      required updating and maintenance of information, and WM load was manipulated by
      varying presence of distracters. RESULTS: There were main effects of group and WM
      load, no significant effect of sex, and a marginal interaction of group by WM
      load, with larger between-group differences in conditions with higher WM load.
      VSIT scores for the condition with the highest WM load were significantly
      correlated with scores on the first trial of the California Verbal Learning Test.
      CONCLUSIONS: We replicated findings of lower scores in adults with TBI on a video
      based ToM task, and provided additional evidence of the effect of WM load on
      social cognition task performance. There were no significant accuracy differences
      between men and women, inconsistent with prior evidence - including our own data
      using the same test. There is strong evidence of a female advantage on other
      social cognition tasks, and the parameters of this advantage remain to be
      discovered.

PMID- 29366950
TI  - Human behavioural discrimination of human, chimpanzee and macaque affective
      vocalisations is reflected by the neural response in the superior temporal
      sulcus.
AB  - Accurate perception of the emotional content of vocalisations is essential for
      successful social communication and interaction. However, it is not clear whether
      our ability to perceive emotional cues from vocal signals is specific to human
      signals, or can be applied to other species' vocalisations. Here, we address this
      issue by evaluating the perception and neural response to affective vocalisations
      from different primate species (humans, chimpanzees and macaques). We found that
      the ability of human participants to discriminate emotional valence varied as a
      function of phylogenetic distance between species. Participants were most
      accurate at discriminating the emotional valence of human vocalisations, followed
      by chimpanzee vocalisations. They were, however, unable to accurately
      discriminate the valence of macaque vocalisations. Next, we used fMRI to compare
      human brain responses to human, chimpanzee and macaque vocalisations. We found
      that regions in the superior temporal lobe that are closely associated with the
      perception of complex auditory signals, showed a graded response to affective
      vocalisations from different species with the largest response to human
      vocalisations, an intermediate response to chimpanzees, and the smallest response
      to macaques. Together, these results suggest that neural correlates of
      differences in the perception of different primate affective vocalisations are
      found in auditory regions of the human brain and correspond to the phylogenetic
      distances between the species.

PMID- 29366951
TI  - Novel procedures for whole organism detection and quantification of fluorescence
      as a measurement for oxidative stress in zebrafish (Danio rerio) larvae.
AB  - The modes of action of pollutants are diverse, and a common consequences to
      pollutant exposure is oxidative stress. This phenomenon is caused by an imbalance
      or disurption in the control of Reactive Oxygen Species (ROS) resulting in an
      accumulation of free radicals. Oxidative stress may cause damages to the DNA,
      phospholipids and proteins, and lead to cell death. Due to the possible
      contribution of oxidative stress to pollutant toxicity, it is valuable to assess
      its occurrence, role and mechanism. Detection of oxidative stress at low
      concentrations soon after the onset of exposure can be a sensitive, general
      marker for contamination. This study aimed at developing and benchmarking a set
      of novel fluorescence-based procedures to assess the occurrence of oxidative
      stress in zebrafish larvae (96 hpf) by measuring the antioxidant glutathione
      (GSH) and general ROS. Zebrafish larvae were exposed to tert-butyl hydroperoxide
      (t-BHP). ROS and GSH were made visible by means of specific fluorescent molecular
      probes in different experimental scenarios. The induction was qualified using
      microscopy and quantified through photometric measurement. For quantitative
      assessment, an approach based on homogenized larvae and a non-invasive plate
      assay were developed. The novel procedures proved suitable for oxidative stress
      detection. Comparisons of qualitative to quantitative data showed that the
      orientation of the larvae in the well can influence fluorescence data evaluation.
      The non-invasive quantitative assay proved robust against any influence of the
      orientation of the larvae. The developed protocols promise to be useful tools for
      the detection of oxidative stress in zebrafish larvae.

PMID- 29366953
TI  - Ecological and health risks assessment and spatial distribution of residual heavy
      metals in the soil of an e-waste circular economy park in Tianjin, China.
AB  - Ziya Circular Economy Park is the biggest e-waste recycle park in North China
      before 2011, its function was then transformed in response to regulations and
      rules. In this paper, investigation was conducted to research the residual
      concentrations of 14 analytes (12 heavy metals and 2 non-metals) in the surface
      soil of Ziya Circular Economy Park and surrounding area. Both ecological and
      health assessments were evaluated using GI (geo-accumulation index) and NPI
      (Nemerow pollution index), and associated health risk was assessed by using USEPA
      model. According to the ecological risk assessment, Cu, Sb, Cd, Zn and Co were
      seriously enriched in the soil of the studied area. The health risk assessment
      proposed by USEPA indicated no significant health risks to the population. Soil
      properties, such as pH and organic matter, were found to correlate with the
      enrichment of heavy metals. Arsenic concentrations in the soil were found
      positively correlated to dead bacteria concentrations. Spatial distribution of
      heavy metals revealed that Ziya Circular Economy Park was the dominant pollution
      source in the studied area. Findings in this study suggest that enough attention
      should be payed to the heavy metal pollution in Ziya Circular Economy Park.

PMID- 29366954
TI  - Evaluating heavy metal accumulation and potential risks in soil-plant systems
      applied with magnesium slag-based fertilizer.
AB  - Two typical Chinese soils including southern paddy soil and northern calcareous
      soils were used in a pot experiment to evaluate the effect of magnesium slag
      based fertilizer on heavy metal accumulation and health risk in soil-plant
      system. The results indicated that magnesium slag-based fertilizer promoted the
      growth of maize plants. The concentrations of Cr, Cu, Pb and Zn in both soils
      amended with magnesium slag-based fertilizer were qualified for the second level
      criterion of Standard of Soil Environment (GB 15618-2009). Accumulation of HMs
      exhibited partitioning characteristics in maize plants, i.e. Cr and Cu were
      accumulated mainly in root and leaf parts while Pb was concentrated in roots. The
      order of transfer factors (TF) of HMs in different plant organs was ordered as
      follows: root > stem > leaf > grain. It indicated that less HMs were accumulated
      in the grain compared with that in other organs. The estimate daily intakes and
      total target hazard quotient of HMs including Cr, Cu, Pb, and Zn were less than
      1, indicating that consumption of maize grain was at low risk and would not cause
      non-carcinogenic risks. From the above results, application of magnesium slag
      based fertilizer at present level would not cause pollution risk for maize plants
      cultivated in two Chinese soils.

PMID- 29366952
TI  - An overview on the removal of synthetic dyes from water by electrochemical
      advanced oxidation processes.
AB  - Wastewater containing dyes are one of the major threats to our environment.
      Conventional methods are insufficient for the removal of these persistent organic
      pollutants. Recently much attention has been received for the oxidative removal
      of various organic pollutants by electrochemically generated hydroxyl radical.
      This review article aims to provide the recent trends in the field of various
      Electrochemical Advanced Oxidation Processes (EAOPs) used for removing dyes from
      water medium. The characteristics, fundamentals and recent advances in each
      processes namely anodic oxidation, electro-Fenton, peroxicoagulation, fered
      Fenton, anodic Fenton, photoelectro-Fenton, sonoelectro-Fenton, bioelectro-Fenton
      etc. have been examined in detail. These processes have great potential to
      destroy persistent organic pollutants in aqueous medium and most of the studies
      reported complete removal of dyes from water. The great capacity of these
      processes indicates that EAOPs constitute a promising technology for the
      treatment of the dye contaminated effluents.

PMID- 29366955
TI  - PBDEs and novel brominated flame retardants in road dust from northern Vietnam:
      Levels, congener profiles, emission sources and implications for human exposure.
AB  - Polybrominated diphenyl ethers (PBDEs) and selected novel brominated flame
      retardants (NBFRs) were examined in road dust samples collected from three
      representative areas in northern Vietnam, including seven inner districts of
      Hanoi metropolitan area, an industrial park in Thai Nguyen province and a rural
      commune in Bac Giang province. This study aims to provide basic information on
      the contamination status, potential sources and human exposure to PBDEs and NBFRs
      associated with road dust in northern Vietnam. PBDEs were detected in all the
      samples at a range of 0.91-56 ng g-1 with a median value of 16 ng g-1. PBDE
      concentrations in road dusts from urban sites were significantly higher than
      those from industrial zone and rural area, suggesting their environmental load
      related to urbanization in northern Vietnam. BDE-209, major component of deca-BDE
      technical mixtures, dominated the congener patterns in all samples, accounting
      for 60.8-91.9% of total PBDE levels. Decabromodiphenyl ethane, an alternative of
      deca-BDE, was observed in a detection frequency of 100% in urban and industrial
      areas and at levels comparable to those of BDE-209. Other NBFRs such as
      pentabromoethylbenzene, hexabromobiphenyl and 1,2-bis-(2,4,6
      tribromophenoxy)ethane, were found at trace levels. Daily intake doses of PBDEs
      via road dust ingestion from 2.3 * 10-5 to 0.11 ng kg-bw-1 d-1 were estimated for
      residents in study areas, indicating a negligible risk with hazard indexes of 10
      9 to 10-5 for selected congeners such as BDE-47, 99, 153 and 209.

PMID- 29366956
TI  - Insight into effects of antibiotics on reactor performance and evolutions of
      antibiotic resistance genes and microbial community in a membrane reactor.
AB  - A lab-scale anoxic/oxic-membrane bioreactor was designed to treat antibiotics
      containing wastewater at different antibiotics concentrations (0.5 mg/L, 1 mg/L
      and 3 mg/L of each antibiotic). Overall COD and NH4+N removal (more than 90%)
      were not affected during the exposure to antibiotics and good TN removal was also
      achieved, while TP removal was significantly affected. The maximum removal
      efficiency of penicillin and chlorotetracycline reached 97.15% and 96.10%
      respectively due to strong hydrolysis, and sulfamethoxazole reached 90.07% by
      biodegradation. However, 63.87% of norfloxacin maximum removal efficiency was
      achieved mainly by sorption. The system had good ability to reduce ARGs, peaking
      to more than 4 orders of magnitude, which mainly depended on the biomass
      retaining of the membrane module. Antibiotics concentration influenced the
      evolution of ARGs and bacterial communities in the reactor. This research
      provides great implication to reduce ARGs and antibiotics in antibiotics
      containing wastewater using A/O-MBR.

PMID- 29366957
TI  - Antibiotics in the aquatic environment of Vietnam: Sources, concentrations, risk
      and control strategy.
AB  - The presence of antibiotics in the aquatic environment is a serious concern
      because it may lead to the emergence of antibiotic resistance, thus lowering the
      therapeutic effect of antibiotics. In Vietnam, the problem is aggravated by the
      irrational use of antibiotics in different sectors of agriculture and human
      health service. Moreover, the residues of antibiotics in the aquatic environment
      can be spread widely due to the lack of proper wastewater treatment systems. In
      this paper, we aim to comprehensively review all relevant sources that discharge
      antibiotics to the aquatic environment in Vietnam. Apart from the common source
      of antibiotics from aquaculture, other activities that release considerable
      amounts of antibiotics into water environment are also included. Environmental
      concentrations of antibiotics related to those sources are studied to demonstrate
      their contributions to the presence of antibiotics in the aquatic environment in
      Vietnam. As antibiotic-contained water may be used as water supply for irrigation
      and even human consumption in rural areas, the essence of wastewater treatment is
      highlighted. Finally, we also discuss the new National Action plan from the
      Ministry of Health for controlling the issue of antibiotic resistance in Vietnam.

PMID- 29366958
TI  - Trace elements in ALS patients and their relationships with clinical severity.
AB  - An exploratory study of trace elements in ALS and their relationships with
      clinical severity was detected. Amyotrophic lateral sclerosis (ALS) is a
      neurodegenerative disorder that causes irreversible damage in humans, with the
      consequent loss of function of motoneurons (MNs), with a prognosis up to 5 years
      after diagnosis. Except to genetic rare cases it is not known the etiology of the
      disorder. Aim of our research is to investigate the possible role of heavy metals
      in the severity of the disease. In this study, by the use of plasma mass (ICP
      MS), we have analyzed the content of essential and heavy metals such: Pb, Cd, Al,
      Hg, Mn, Fe, Cu, Zn, Se, Mg, and Ca, in blood, urine and hair of ALS patients and
      controls; moreover we divided the patients in two groups for disease severity and
      analyzed the difference among the groups, in order to study a possible
      involvement of metals in the severity of the damage. Our results suggest a
      protective role of Selenium, involved in protective antioxidant mechanisms, and a
      risk factor in the case of presence of Lead in blood. The levels of the other
      metals are not easy to interpret, because these may be due to life style and for
      essential metals a consequence of the disease condition, not a cause.

PMID- 29366959
TI  - Membrane fouling control and enhanced removal of pharmaceuticals and personal
      care products by coagulation-MBR.
AB  - We investigated the effects of the addition of two coagulants-polyaluminium
      chloride (PACl) and chitosan-into the membrane bioreactor (MBR) process on
      membrane fouling and the removal of pharmaceuticals and personal care products
      (PPCPs). Their addition at optimized dosages improved the permeability of the
      membrane by reducing the concentration of soluble microbial products in mixed
      liquor, the content of inorganic elements, and irreversible fouling of the
      membrane surface. During long-term operation, the addition of PACl increased
      removal efficiencies of tetracycline, mefenamic acid, atenolol, furosemide,
      ketoprofen, and diclofenac by 17-23%. The comparative evaluation using mass
      balance calculations between coagulation-MBR (with PACl addition) and control-MBR
      (without PACl addition) showed that enhanced biodegradability played a key role
      in improving removal efficiencies of some PPCPs in coagulation-MBR. Coagulation
      MBR also had higher oxygen uptake rates and specific nitrification rates of
      microorganisms. Overall, our findings suggest that the combination of MBR with
      coagulation reduced membrane fouling, lengthening operation period of the
      membrane, and improved the removal of some PPCPs as a result of enhanced
      biodegradability.

PMID- 29366960
TI  - Predicting tumour growth and its impact on survival in gemcitabine-treated
      patients with advanced pancreatic cancer.
AB  - The aim of this evaluation was to characterize the impact of the tumour size (TS)
      effects driven by the anticancer drug gemcitabine on overall survival (OS) in
      patients with advanced pancreatic cancer by building and validating a predictive
      semi-mechanistic joint TS-OS model. TS and OS data were obtained from one phase
      II and one phase III study where gemcitabine was administered (1000-1250 mg/kg
      over 30-60 min i.v infusion) as single agent to patients (n = 285) with advanced
      pancreatic cancer. Drug exposure, TS and OS were linked using the population
      approach with NONMEM 7.3. Pancreatic tumour progression was characterized by
      exponential growth (doubling time = 67 weeks), and tumour response to treatment
      was described as a function of the weekly area under the gemcitabine triphosphate
      concentration vs time curve (AUC), including treatment-related resistance
      development. The typical predicted percentage of tumour growth inhibition with
      respect to no treatment was 22.3% at the end of 6 chemotherapy cycles. Emerging
      resistance elicited a 57% decrease in drug effects during the 6th chemotherapy
      cycle. Predicted TS profile was identified as main prognostic factor of OS, with
      tumours responders' profiles improving median OS by 30 weeks compared to stable
      disease TS profiles. Results of NCT00574275 trial were predicted using this
      modelling framework, thereby validating the approach as a prediction tool in
      clinical development. Our analyses show that despite the advanced stage of the
      disease in this patient population, the modelling framework herein can be used to
      predict the likelihood of treatment success using early clinical data.

PMID- 29366961
TI  - Inkjet printing of paracetamol and indomethacin using electromagnetic technology:
      Rheological compatibility and polymorphic selectivity.
AB  - Drop-on-demand inkjet printing is a potential enabling technology both for
      continuous manufacturing of pharmaceuticals and for personalized medicine, but
      its use is often restricted to low-viscosity solutions and nano-suspensions. In
      the present study, a robust electromagnetic (valvejet) inkjet technology has been
      successfully applied to deposit prototype dosage forms from solutions with a wide
      range of viscosities, and from suspensions with particle sizes exceeding 2 MUm. A
      detailed solid-state study of paracetamol, printed from a solution ink on
      hydroxypropyl methylcellulose (HPMC), revealed that the morphology of the
      substrate and its chemical interactions can have a considerable influence on
      polymorphic selectivity. Paracetamol ink crystallized exclusively into form II
      when printed on a smooth polyethylene terephthalate substrate, and exclusively
      into form I when in sufficient proximity to the rough surface of the HPMC
      substrate to be influenced by confinement in pores and chemical interactions. The
      relative standard deviation in the strength of the dosage forms was <4% in all
      cases, for doses as low as 0.8 mg, demonstrating the accuracy and reproducibility
      associated with electromagnetic inkjet technology. Good adhesion of indomethacin
      on HPMC was achieved using a suspension ink with hydroxypropyl cellulose, but not
      on an alternative polyethylene terephthalate substrate, emphasising the need to
      tailor the binder to the substrate. Future work will focus on lower-dose drugs,
      for which dosing flexibility and fixed dose combinations are of particular
      interest.

PMID- 29366962
TI  - Accessing lipophilicity of drugs with biomimetic models: A comparative study
      using liposomes and micelles.
AB  - Lipophilicity is a physicochemical property of crucial importance in drug
      discovery and drug design. Biomimetic models, such as liposomes and micelles,
      constitute a valuable tool for the assessment of lipophilicity through the
      determination of partition coefficients (log Kp). However, the lack of
      standardization hampers the judgment about which model or method has the best and
      broadest passive drug permeation predictive capacity. This work provides a
      comparative analysis between the methodologies based on biomimetic models to
      determine the partition coefficient (log Kp). For that purpose, a set of
      reference substances preconized by the Organization for Economic Cooperation and
      Development (OECD) guidelines was used. The biomimetic models employed were
      liposomes and micelles composed by 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine
      (DMPC) and hexadecylphosphocholine (HePC), respectively. Both lipids were used as
      representative phospholipids of natural membranes. The partition coefficients
      between biomimetic models and aqueous phases were determined by derivative
      spectroscopy at physiological conditions (37  degrees C and pH 7.4). The
      partition coefficients obtained using biomimetic models are quite different and
      more reliable than the ones obtained using an octanol/water system. Comparing the
      performance of the two biomimetic models, micelles revealed to be suitable only
      for substances with high molar absorption coefficient and log Kp > 3, but in
      general liposomes are the best model for accessing lipophilicity of drugs.
      Furthermore, a comparison between experimental data and the partition
      coefficients determined by the computational method COSMOmic is also provided and
      discussed. As a final summarizing result, a decision tree is provided in order to
      guide the selection of a tool for assessing the lipophilicity of drugs.

PMID- 29366963
TI  - Functional characterization of cell-free expressed Kv1.3 channel using a voltage
      sensitive fluorescent dye.
AB  - Using a cell-free expression system, we produced the Kv1.3 protein embedded in
      one step within detergent micelles. The protein was then purified and relipidated
      into mixed lipid bilayers. These proteoliposomes held an average of 0.8 protein
      per liposome. We examined channel forming activity using an oxonol VI fluorescent
      probe and verified its inhibition using margatoxin and ShK toxins. This assay was
      automatized and optimized so as to get a Z' statistical factor acceptable for
      venom fraction screening. We obtained a sensible amount of membrane protein using
      the cell-free assay, that proved to be active when embedded in liposomes. These
      findings emphasize the quality of the cell-free produced KV1.3 proteoliposomes
      and the usefulness of a fluorescent probe. This method can benefit the field of
      channel characterization, as well as provide tools for the development of new
      inhibitors, so as to reinforce our therapeutic arsenal against autoimmune
      diseases.

PMID- 29366965
TI  - Improved heterologous expression of the membrane-bound quinoprotein quinate
      dehydrogenase from Gluconobacter oxydans.
AB  - Gluconobacter oxydans produces 3-dehydroquinate by oxidation of quinate through a
      reaction catalyzed by the quinate dehydrogenase (QDH), membrane-bound,
      pyrroloquinoline quinone (PQQ)-dependent dehydrogenase. We previously reported
      the nucleotide and deduced amino acid sequence of QDH and constructed a
      heterologous expression system of QDH in Pseudomonas sp. (A.S. Vangnai, W.
      Promden, W. De-Eknamkul, K. Matsushita, H. Toyama, Biochemistry (Moscow) 75:452
      459, 2010). Through this study, we aim to update the sequences of QDH and improve
      the heterologous expression of QDH in Gluconobacter strains using a broad-host
      range plasmid. Expression of QDH using a plasmid containing a long 5'-UTR was
      higher than that using a plasmid with a short 5'-UTR. In addition, the usage of
      the putative promoter region of the membrane-bound, alcohol dehydrogenase (ADH)
      of Gluconobacter resulted in higher expression levels compared to the usage of
      the lacZ promoter. Base substitution experiments allowed to identify the correct
      TTG initiation codon between two possibilities, and the result of these
      experiments were consistent with the N-terminal amino acid sequence of the
      expressed QDH. However, change of the TTG codon to ATG did not increase QDH
      expression. Therefore, the optimal plasmid for QDH expression included the
      structural gene with a long 5'-UTR and the ADH promoter. Cell membrane of the
      recombinant Gluconobacter strain presented approximately 10-times higher specific
      QDH activity than that observed in the wild-type strain.

PMID- 29366964
TI  - Production and characterization of a novel Delta-like 1 functional unit as a tool
      for Notch pathway activation and generation of a specific antibody.
AB  - Notch signalling is an evolutionary conserved cell-to-cell communication pathway
      crucial for development and tissue homeostasis. Abnormal Notch signalling by
      mutations or deregulated expression of its receptors and/or ligands can lead to
      cancer making it a potential therapeutic target. Delta-like1 (DLL1) is a ligand
      of the Notch pathway implicated in different types of cancer, including breast
      cancer. Herein, we produced rhDLL1-DE3, a novel soluble form of DLL1 protein,
      which contains the DSL domain and EGF1-3 repeats critical for Notch pathway
      activation. cDNA fragments of human DLL1, encoding truncated versions of DLL1
      with regions required to activate Notch receptors, were cloned and expressed as
      histidine-fused proteins in bacterial and mammalian cells. Expression tests in
      mammalian cells showed almost exclusively expression of the rhDLL1-DE3 protein
      form comprising the minimal binding regions DSL to EGF3 to Notch receptors. The
      highest yield of rhDLL1-DE3 was obtained from E. coli inclusion bodies. The
      produced protein, with purity higher than 95% bound to human Notch1 recombinant
      protein, by both Biolayer interferometry and ELISA assays. Cellular assays
      revealed rhDLL1-DE3 was biologically active as it increased expression of Notch
      dependent genes in inducible pluripotent and breast cancer cells. Moreover,
      rhDLL1-DE3 allowed the generation of polyclonal antibodies by immunization that
      efficiently recognized DLL1 proteins by immunoblot, and caused a significant
      decrease of Notch1 expression in MCF7 breast cancer cells. The rhDLL1-DE3 protein
      might thus be used for Notch pathway activation and to generate anti-DLL1
      monoclonal antibodies by immunization or phage display technology to unveil the
      effect of DLL1 in breast cancer.

PMID- 29366966
TI  - Laparoscopic-Assisted Uterus Retrieval From Live Organ Donors for Uterine
      Transplant: Our Experience of Two Patients.
AB  - STUDY OBJECTIVE: To report the first ever laparoscopic-assisted live donor uterus
      retrieval in 2 patients for uterus transplant. DESIGN: Case study (Canadian Task
      Force classification III). SETTING: Galaxy CARE Laparoscopy Institute, Pune,
      India. PATIENTS: Two patients with absolute uterine factor infertility with their
      mothers as donors. INTERVENTIONS: In vitro fertilization and uterine transplant.
      MEASUREMENTS AND MAIN RESULTS: A 12-member team was formed, and approval for
      transplant was obtained from the institutional review board. Pretransplant, in
      vitro fertilization for both patients was done. Two consecutive uterine
      transplants were done on 2 successive days. Vessels were harvested
      laparoscopically in both donors. Uterus and harvested vessels were retrieved by a
      small abdominal incision to prevent injury and infection. The uterus was
      transplanted in the recipients by end to side anastomosis of the harvested
      vessels to external iliac vessels, followed by anchoring of supports of the donor
      uterus to those of the recipients. Surgical intra- and postoperative parameters,
      postoperative investigations, and follow-up data of 6 months were measured.
      Operative time for laparoscopic donor surgery was 4 hours. Bench surgery took 45
      minutes. Recipient surgery time was 4 hours. There were no intraoperative or
      immediate postoperative complications. Both the recipients started menstruating
      after 34 days and 48 days, respectively, and have had 6 cycles of menses at
      regular intervals. Uterine artery Doppler showed good flow in both patients.
      Hysteroscopy-guided cervical biopsies were used as a method of surveillance of
      graft rejection after uterine transplant. Office hysteroscopy was done after 2
      months in both patients, and hysteroscopy-guided endometrial and cervical
      biopsies were taken. Minimal slough was seen on the endometrium in the patient
      with Mayer-Rokitansky-Kuster-Hauser syndrome, which was removed. Repeat
      hysteroscopy after 10 days showed a healthy endometrium. CONCLUSIONS:
      Laparoscopic-assisted uterus donor retrieval is feasible and affords all the
      advantages of a minimally invasive technique, thereby reducing the morbidity of
      the procedure. It helps in better dissection of the vessels, shortens the
      operative time, and helps to minimize tissue handling of the harvested uterus and
      vessels.

PMID- 29366968
TI  - Report of two cases of tocilizumab induced recurrent meningitis or
      meningoencephalitis.

PMID- 29366969
TI  - Acral myxoinflammatory fibroblastic sarcoma simulating rheumatoid bursitis.
      Diffusion-weighted imaging.

PMID- 29366967
TI  - Monepantel is a non-competitive antagonist of nicotinic acetylcholine receptors
      from Ascaris suum and Oesophagostomum dentatum.
AB  - Zolvix(r) is a recently introduced anthelmintic drench containing monepantel as
      the active ingredient. Monepantel is a positive allosteric modulator of DEG-3/DES
      2 type nicotinic acetylcholine receptors (nAChRs) in several nematode species.
      The drug has been reported to produce hypercontraction of Caenorhabditis elegans
      and Haemonchus contortus somatic muscle. We investigated the effects of
      monepantel on nAChRs from Ascaris suum and Oesophagostomum dentatum
      heterologously expressed in Xenopus laevis oocytes. Using two-electrode voltage
      clamp electrophysiology, we studied the effects of monepantel on a nicotine
      preferring homomeric nAChR subtype from A. suum comprising of ACR-16; a
      pyrantel/tribendimidine preferring heteromeric subtype from O. dentatum
      comprising UNC-29, UNC-38 and UNC-63 subunits; and a levamisole preferring
      subtype (O. dentatum) comprising UNC-29, UNC-38, UNC-63 and ACR-8 subunits. For
      each subtype tested, monepantel applied in isolation produced no measurable
      currents thereby ruling out an agonist action. When monepantel was continuously
      applied, it reduced the amplitude of acetylcholine induced currents in a
      concentration-dependent manner. In all three subtypes, monepantel acted as a non
      competitive antagonist on the expressed receptors. ACR-16 from A. suum was
      particularly sensitive to monepantel inhibition (IC50 values: 1.6 +/- 3.1 nM and
      0.2 +/- 2.3 MUM). We also investigated the effects of monepantel on muscle flaps
      isolated from adult A. suum. The drug did not significantly increase baseline
      tension when applied on its own. As with acetylcholine induced currents in the
      heterologously expressed receptors, contractions induced by acetylcholine were
      antagonized by monepantel. Further investigation revealed that the inhibition was
      a mixture of competitive and non-competitive antagonism. Our findings suggest
      that monepantel is active on multiple nAChR subtypes.

PMID- 29366970
TI  - Leaf fatty acid remodeling in the salt-excreting halophytic grass Spartina patens
      along a salinity gradient.
AB  - Spartina patens is a highly dispersed halophytic grass invader in Mediterranean
      marshes. It is also characterized by having a high degree of resistance to
      salinity, one of the main drivers of plant zonation in salt marshes.
      Nevertheless, the physiological basis behind the extreme resistance of S. patens
      requires more detailed studies. In the present work, we aimed to study how
      membrane fatty acid remodeling could contribute to the resistance of this plant
      to salt. Spartina patens individuals exposed to increasing levels of salinity and
      its leaf fatty acid profile under lipid peroxidation products evaluated under all
      tested concentrations. A significant increase in the relative amounts of the
      saturated fatty acids (SFA) was observed, namely palmitic acid (C16:0), essential
      for PS II functioning, and stearic (C18:0) acid. The chloroplastidial trans
      hexadecenoic acid (C16:1t) as well as the polyunsaturated linoleic (C18:2) and
      linolenic (C18:3) acids showed significant decreases in all the salt treatments.
      These changes led to a reduction in the double bond index in salt-treated plants
      which reflects reduction of the fluidity of the chloroplast membranes, which
      could contribute to maintain the membrane impermeable to the toxic exogenous Na.
      Despite the decrease observed in the total fatty acid contents in plants exposed
      to high salt concentrations the amounts of lipid peroxidation products decreased
      highlighting the resistance of this species towards toxic exogenous salt
      concentrations. Membrane fatty acid remodeling could represent an efficient
      mechanism to maintain the photosynthetic machinery of S. patens highly efficient
      under salt stress.

PMID- 29366971
TI  - Lipid production in aquatic plant Azolla at vegetative and reproductive stages
      and in response to abiotic stress.
AB  - The aquatic plant Azolla became increasingly popular as bioenergy feedstock
      because of its high growth rate, production of biomass with high levels of
      biofuel-producing molecules and ability to grow on marginal lands. In this study,
      we analysed the contribution of all organs of Azolla to the total yield of lipids
      at vegetative and reproductive stages and in response to stress. Triacylglycerol
      containing lipid droplets were detected in all (vegetative and reproductive)
      organs with the highest level in the male microsporocarps and microspores. As a
      result, significantly higher total yields of lipids were detected in Azolla
      filiculoides and Azolla pinnata at the reproductive stage. Starving changed the
      yield and composition of the fatty acid as a result of re-direction of carbon
      flow from fatty acid to anthocyanin pathways. The composition of lipids, in
      regard the length and degree of unsaturation of fatty acids, in Azolla meets most
      of the important requirements for biodiesel standards. The ability of Azolla to
      grow on wastewaters, along with their high productivity rate, makes it an
      attractive feedstock for the production of biofuels.

PMID- 29366972
TI  - Differences in the enzymatic hydrolysis of glucosinolates increase the defense
      metabolite diversity in 19 Arabidopsis thaliana accessions.
AB  - Plants of the order Brassicales produce glucosinolates (GS), a group of secondary
      metabolites that are part of an elaborate defense system. But it is not the GS
      itself rather its enzymatic hydrolysis products that cause the bioactive effects
      protecting the plants against pests and pathogens. Thus the enzymatic hydrolysis
      and a variety of additional influential factors determine the structural outcome
      of the GS degradation process. To evaluate the possible diversity of defense
      metabolites a range of 19 Arabidopsis thaliana accessions were selected showing
      divergence in their geographical origin, in their phenotype, and in their GS
      profile. These particular accessions accumulate several alkenyl GS, hydroxyalkyl
      GS, methylthioalkyl GS, and methylsulfinylalkyl GS in their rosette leaves
      whereas the indole GS contents are relatively invariant, as analyzed by UHPLC
      DAD. After tissue disruption the enzymatic formation of GS hydrolysis products
      was examined and breakdown products were identified and quantified by GC-MS.
      Great differences in the amount and structure of volatile enzymatic degradation
      products could be observed in the different accessions, with strong variation in
      formation of epithionitriles, nitriles, and isothiocyanates. The occurrence of
      specific GS hydrolysis products was put in relation to relative gene expression
      profiles of myrosinases and specifier proteins as measured by RT-qPCR, and in
      relation to relative protein abundance of epithiospecifier protein. Dependent on
      the different GS profiles and reliant on degradation protein abundance and
      composition the ecotypes strongly varied in their ability to form
      isothiocyanates, nitriles and epithionitriles, thus increasing the plants'
      equipment of defense metabolites.

PMID- 29366973
TI  - Leaf non-structural carbohydrate allocation and C:N:P stoichiometry in response
      to light acclimation in seedlings of two subtropical shade-tolerant tree species.
AB  - : Light availability greatly affects plant growth and development. In shaded
      environments, plants must respond to reduced light intensity to ensure a regular
      rate of photosynthesis to maintain the dynamic balance of nutrients, such as leaf
      non-structural carbohydrates (NSCs), carbon (C), nitrogen (N) and phosphorus (P).
      To improve our understanding of the nutrient utilization strategies of understory
      shade-tolerant plants, we compared the variations in leaf NSCs, C, N and P in
      response to heterogeneous controlled light conditions between two subtropical
      evergreen broadleaf shade-tolerant species, Elaeocarpus sylvestris (E.
      sylvestris) and Illicium henryi (I. henryi). Light intensity treatments were
      applied at five levels (100%, 52%, 33%, 15% and 6% full sunlight) for 30 weeks to
      identify the effects of reduced light intensity on leaf NSC allocation patterns
      and leaf C:N:P stoichiometry characteristics. We found that leaf soluble sugar,
      starch and NSC concentrations in E. sylvestris showed decreasing trends with
      reduced light intensity, whereas I. henryi presented slightly increasing trends
      from 100% to 15% full sunlight and then significant decreases at extremely low
      light intensity (6% full sunlight). The soluble sugar/starch ratio of E.
      sylvestris decreased with decreasing light intensity, whereas that of I. henryi
      remained stable. Moreover, both species exhibited increasing trends in leaf N and
      P concentrations but limited leaf N:P and C:P ratio fluctuations with decreasing
      light intensity, revealing their adaptive strategies for poor light environments
      and their growth strategies under ideal light environments. There were highly
      significant correlations between leaf NSC variables and C:N:P stoichiometric
      variables in both species, revealing a trade-off in photosynthesis production
      between leaf NSC and carbon allocation. Thus, shade-tolerant plants readjusted
      their allocation of leaf NSCs, C, N and P in response to light acclimation.
      Redundancy analysis showed that leaf morphological features of both E. sylvestris
      and I. henryi affected their corresponding leaf nutrient traits. These results
      improve our understanding of the dynamic balance between leaf NSCs and leaf C, N
      and P components in the nutritional metabolism of shade-tolerant plants. KEY
      MESSAGE: Two species of understory shade-tolerant plants responded differently to
      varying light intensities in terms of leaf non-structural carbohydrate allocation
      and the utilization of carbon, nitrogen and phosphorus to balance nutritional
      metabolism and adapt to environmental stress.

PMID- 29366974
TI  - Obesity linking to hepatocellular carcinoma: A global view.
AB  - Hepatocellular carcinoma (HCC) is the commonest primary liver cancer and the
      second leading cause of cancer death worldwide. Obesity is rapidly becoming
      pandemic and associated with increased carcinogenesis. In this review, we
      describe the obesity-related factors that influence the development of HCC. We
      provide evidence of strong links between neural regulation, endocrine and HCC in
      obesity. We discuss recent advances in our understanding of how adipose tissue
      alters hepatic metabolism and immune response in HCC development through inter
      organ communication. Taken together, our review aims to provides a concise and up
      to date summary about the connection between obesity and HCC, with emphasis on
      the opportunities for effective strategies in preventing the development of HCC
      in obese individuals.

PMID- 29366975
TI  - Evaluation and comparison of epidural analgesia in labour related information on
      French and English-speaking websites.
AB  - OBJECTIVES: The medical information on the Internet is better in English than in
      other languages. The information about Epidural Analgesia In Labour (EAIL)
      available on French-speaking websites is of poor quality. The quality of the
      information about EAIL should be better in English, but there is no comparison
      available. This study has assessed and compared the quality of the information
      about EAIL available on French and English-speaking websites. METHOD: Keywords
      "epidural", "epidurale" and/or "peridurale" were used in the French, Canadian and
      American Google(r) and Yahoo(r) search engines. Two independent assessors
      assessed the 20 first websites for each engine search. They used an evaluation
      form created from French, Canadian and American recommendations. This form
      assessed the structure quality (Structure Score/25) and the medical information
      quality (Medical Information Score/30) of the websites. The addition of both
      scores gives the Global Score (/55). RESULTS: Seventy-one websites were assessed,
      39 French-speaking and 32 English-speaking websites. Structure, Medical
      Information and Global Scores (expressed as mean (SD)) were respectively 11 (4),
      13 (5), 24 (8) for the French-speaking websites and 11 (4), 12 (4), 23 (7) for
      the English-speaking websites. There was no statistical significant difference
      between both languages. CONCLUSION: Information about EAIL available on French
      and English-speaking websites is of poor quality and there is no difference in
      the information quality, whatever the language. A consideration on Internet
      medical information improvement is needed. A high quality dedicated website
      should be created and broadcasted.

PMID- 29366976
TI  - Synergistic interplay between the two major bone minerals, hydroxyapatite and
      whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem
      cells.
AB  - : The inorganic part of human bone is mainly composed of hydroxyapatite (HAP:
      Ca10(PO4)6(OH)2) and whitlockite (WH: Ca18Mg2(HPO4)2(PO4)12) minerals, where the
      WH phase occupies up to 20-35% of total weight. These two bone minerals have
      different crystal structures and physicochemical properties, implying their
      distinguished role in bone physiology. However, until now, the biological
      significance of the presence of a certain ratio between HAP and WH in bone is
      unclear. To address this fundamental question, bone mimetic scaffolds are
      designed to encapsulate human mesenchymal stem cells (MSCs) for assessing their
      osteogenic activity depending on different ratios of HAP and WH. Interestingly,
      cellular growth and osteogenic differentiation are significantly promoted when
      MSCs are grown with a 3-1 ratio of HAP and WH nanoparticles, which is similar to
      bone. One of the reasons for this synergism between HAP and WH in hydrogel
      scaffolds is that, while WH nanoparticles can enhance osteogenic differentiation
      of MSCs compared to HAP, WH counterintuitively decreases the mechanical stiffness
      of nanocomposite hydrogels and hinders the osteogenic activity of cells. Taken
      together, these findings identify the optimal ratio between two major minerals in
      bone mimetic scaffolds to maximize the osteogenic differentiation of MSCs.
      STATEMENT OF SIGNIFICANCE: Human bone minerals are composed of HAP and WH
      inorganic nanoparticles which have different material properties. However, the
      reason for the coexistence of HAP and WH in human bone is not fully identified,
      and HAP and WH composite biomaterial has not been utilized in the clinic. In this
      study, we have developed bone mimetic HAP and WH nanocomposite hydrogel scaffolds
      with various ratios. Importantly, we found out that HAP can promote the
      mechanical stiffness of the composite hydrogel scaffolds while WH can enhance the
      osteogenic activity of stem cells, which together induced synergism to maximize
      osteogenic differentiation of stem cells when mixed into 3-1 ratio that is
      similar to human bone.

PMID- 29366978
TI  - Safety and efficacy of nintedanib in idiopathic pulmonary fibrosis: A real-life
      observational study in Greece.
AB  - BACKGROUND: Nintedanib represents an antifibrotic compound able to slow down
      disease progression of patients with idiopathic pulmonary fibrosis (IPF).
      OBJECTIVE: To investigate the safety and efficacy of nintedanib in patients with
      IPF in a real-life setting. METHODS: This was a multicentre, retrospective,
      observational, real-life study for patients with IPF receiving nintedanib between
      October 2014 and October 2016. RESULTS: We identified 94 patients with IPF
      receiving nintedanib (72 males, mean age+/-SD: 73.8 +/- 7.5, mean%FVC+/-SD = 68.1
      +/- 18.3, mean%DLCo+/-SD = 44.4 +/- 14.5). Diarrhea (n = 52, 55.3%) was the most
      commonly reported adverse event. Twenty patients (21.2%) had to permanently
      discontinue nintedanib due to severe adverse events. In the 6-months follow-up,
      median decline in %FVC predicted and %DLCO predicted were 1.36 (95%Cl: 0 to 2.97)
      and 4.00 (95%Cl: 2.01 to 6.20), respectively, when deaths were censored and
      excluded from the analysis. At 12 months, mean%FVC+/-SD and mean%DLCo+/-SD were
      64.5 +/- 19.1 and 43.7 +/- 15.4, respectively. With regards to mortality, 17
      patients (18.1%) died over a study period of 730 days. CONCLUSION: Nintedanib
      demonstrated an acceptable safety and efficacy profile in our real-world
      observational study. Prospective observational studies in the context of
      registries that collect well-defined supporting data over time are sorely needed
      to answer residual questions on drug's performance.

PMID- 29366979
TI  - Gastrocnemius fascicle and achilles tendon length at the end of the eccentric
      phase in a single and multiple countermovement hop.
AB  - The purpose of this investigation was to compare fascicle and tendon length of
      the gastrocnemius at the end of the eccentric phase during a hop utilizing a
      single countermovement (sCM) versus multiple countermovement (mCM1, mCM2, mCM3)
      strategy. Seventeen healthy males performed nine hopping trials of sCM and nine
      trials of mCM. Ankle and knee joint angle and lower leg length from videography
      and muscle ultrasound were used to calculate muscle-tendon unit (MTU), fascicle
      and tendon length. Sacral marker data was used to determine hopping height. Force
      and displacement-time curves were utilized to calculate work. Muscle activity of
      the lateral and medial gastrocnemius was also measured. Fascicle length was
      significantly shorter (mCM3: 6.2 +/- 1.5 cm, sCM: 7.3 +/- 2.0 cm) and tendon
      length was significantly longer (mCM3: 36.5 +/- 3.6 cm, sCM: 35.5 +/- 3.8 cm) at
      the end of the eccentric phase in mCM3 in comparison to sCM. Maximal hopping
      height (mCM: 14.6 +/- 3.1 cm, sCM: 13.1 +/- 2.5 cm), eccentric phase
      gastrocnemius muscle activity (mCM medial gastrocnemius: 0.10 +/- 0.03 mV, mCM
      lateral gastrocnemius: 0.08 +/- 0.04 mV, sCM medial gastrocnemius: 0.07 +/- 0.03
      mV, sCM lateral gastrocnemius: 0.05 +/- 0.04 mV), and both eccentric (mCM3: 46.6
      +/- 19.4 J, sCM: 38.5 +/- 15.9 J) and concentric work (mCM3: 87.6 +/- 26.5 J,
      sCM: 80.9 +/- 27.6 J) were significantly higher for mCM3 compared to sCM. The
      results indicate that a multiple countermovement hop strategy results in shorter
      fascicle length and longer tendon length at the end of the eccentric phase. In
      addition, greater eccentric phase muscle activity during the third
      countermovement (mCM3) in comparison to a single countermovement hop (sCM) was
      observed. A multiple countermovement strategy appears to result in higher hopping
      height and greater work done in both the eccentric and concentric phase
      indicating possible contribution of stored-elastic energy from the tendon.

PMID- 29366980
TI  - Combining behavior and EEG analysis for exploration of dynamic effects of ADHD
      treatment in animal models.
AB  - BACKGROUND: We analyze the dynamics of rodent EEG amplitude in an experiment
      accompanied by video recordings. Brain activity of animals is commonly acquired
      together with a video of behavior, but recordings are rarely combined in
      analysis. The data acquired is most commonly analyzed separately. To our
      knowledge, no study has used behavior to improve the analysis of EEG waveforms,
      specifically for artifact removal - other than through manual editing. COMPARISON
      WITH EXISTING METHOD(S): We explore two approaches: a traditional approach that
      relies on data preprocessing and artifact rejection by an expert; and an
      alternative approach that combines analysis of EEG with behavior extracted from
      video recordings. NEW METHOD: We use the level of activity extracted from the
      behavioral video as a measure of confidence in the acquired EEG waveform, and as
      a weighting factor in averaging and statistical comparisons. RESULTS: We find in
      analysis of the EEG that the two approaches lead to similar conclusions, but the
      analysis leveraging behavioral data achieves this while avoiding many subjective
      choices often required for artifact rejection and data preprocessing.
      CONCLUSIONS: The methods we describe allow for the inclusion of all recorded data
      in the analysis, thereby making statistical tests more friendly to
      interpretation, and making the data processing transparent and reproducible.

PMID- 29366977
TI  - The imidazoline I2 receptor agonist 2-BFI attenuates hypersensitivity and spinal
      neuroinflammation in a rat model of neuropathic pain.
AB  - Chronic pain is a large, unmet public health problem. Recent studies have
      demonstrated the importance of neuroinflammation in the establishment and
      maintenance of chronic pain. However, pharmacotherapies that reduce
      neuroinflammation have not been successfully developed to treat chronic pain thus
      far. Several preclinical studies have established imidazoline I2 receptor (I2R)
      agonists as novel candidates for chronic pain therapies, and while some I2R
      ligands appear to modulate neuroinflammation in certain scenarios, whether they
      exert anti-neuroinflammatory effects in models of chronic pain is unknown. This
      study examined the effects of the prototypical I2R agonist 2-(2-benzofuranyl)-2
      imidazoline hydrochloride (2-BFI) on hypersensitivity and neuroinflammation
      induced by chronic constriction injury (CCI), a neuropathic pain model in rats.
      In CCI rats, twice-daily treatment with 10 mg/kg 2-BFI for seven days
      consistently increased mechanical and thermal nociception thresholds, reduced
      GFAP and Iba-1 levels in the dorsal horn of the spinal cord, and reduced levels
      of TNF-alpha relative to saline treatment. These results were recapitulated in
      primary mouse cortical astrocyte cultures. Incubation with 2-BFI attenuated GFAP
      expression and supernatant TNF-alpha levels in LPS-stimulated cultures. These
      results suggest that I2R agonists such as 2-BFI may reduce neuroinflammation
      which may partially account for their antinociceptive effects.

PMID- 29366981
TI  - Rapid in situ biosynthesis of gold nanoparticles in living platelets for
      multimodal biomedical imaging.
AB  - Inspired by the nature, the biomimetic nanomaterial design strategies have
      attracted great interest because the bioinspired nanoplatforms may enhance the
      functionality of current nanoparticles. Especially, the cell membrane-derived
      nanoparticles can more effectively navigate and interact with the complex
      biological microenvironment. In this study, we have explored a novel strategy to
      rapidly in situ biosynthesize gold nanoparticles (GNPs) in living platelets with
      the help of ultrasound energy. Firstly, under the ultrasound exposure, the
      biocompatible chloroauric acid salts (HAuCl4) can be enhanced to permeate into
      the platelet cytoplasm. Then, by the assist of reducing agent (NaBH4 and sodium
      citrate) and platelet enzyme, GNPs were fast in situ synthesized in intra
      platelets. The biosynthesized GNPs had a size of about 5 nm and were uniformly
      distributed in the cytoplasm. Atomic absorption spectrometry (AAS) showed the
      synthesized amount of Au is (12.7 +/- 2.4) * 10-3 pg per one platelet. The GNPs
      in platelets can produce Raman enhancement effect and further be probed for both
      dark-field microscopy (DFM)-based imaging and computed tomography (CT) imaging.
      Moreover, the platelets were not activated and remained aggregation bioactivity
      when intra-platelet GNPs synthesis. Therefore, such mimicking GNPs-platelets with
      in situ GNPs components remain inherent platelet bioactivity will find potential
      theranostic implications with unique GNPs properties.

PMID- 29366982
TI  - Dehydrothermally crosslinked collagen/hydroxyapatite composite for enhanced in
      vivo bone repair.
AB  - Bone repair accounts for a large number of surgical operations. However,
      artificial bone replacement materials do not present the delicate continuing
      adjustment ability like natural bones and cause obvious side effects. Thus,
      materials that induce the regeneration of bones would be an optimal choice to
      repair bone tissues. This study proposes a biocompatible bone repair material
      prepared from crosslinked porous composite of collagen and hydroxyapatite. The
      proposed dehydrothermal method to cross-link the composite avoids use of extra
      chemical reagents for crosslinking and ensures that the materials were prepared
      using only bio-compatible materials. By adjusting the preparative parameters such
      as componential ratios or heating period, materials with a large property space
      could be achieved. Properties including porosity, mechanical strength, and
      swelling ratios could be facilely adjusted, promising its applications in
      personalized medical treatment. Cell experiments and animal experiments
      demonstrate the material presented high biocompatibility and effectively induced
      osteanagenesis in vivo. We expect the proposed material possesses high
      commercialization potential and serves as an effective bone repair material in
      realistic applications.

PMID- 29366983
TI  - N-Halamine polymer from bipolymer to amphiphilic terpolymer with enhancement in
      antibacterial activity.
AB  - A novel N-halamine terpolymer, i.e., P(ADMH-MMA-HEMA)-Cl, with high antibacterial
      efficacies were fabricated via a free-radical copolymerization of 3-allyl-5,5
      dimethylhydantoin(ADMH), methyl methacrylate(MMA), and hydroxyethyl methacrylate
      (HEMA), followed by a chlorination treatment using sodium hypochlorite as
      chlorinating agent. A controllable synthesis of P(ADMH-MMA-HEMA)-Cl was achieved
      by tuning chlorination conditions, such as chlorination temperature, reactant
      concentration, chlorination time, etc. A series of antibacterial assays were
      conducted, and the as-prepared products P(ADMH-MMA-HEMA)-Cl showed good killing
      capabilities against both Gram-positive and Gram negative bacteria. Remarkably,
      compared to N-halamine biopolymer counterparts, e.g., P(ADMH-HEMA)-Cl and P(ADMH
      MMA)-Cl, and the as-prepared N-halamine terpolymer P(ADMH-MMA-HEMA)-Cl presented
      the enhancement in antibacterial efficiency toward pathogens. It is believed that
      this approach offers great potential to be utilized in various fields where
      antibacterial properties are highly required.

PMID- 29366984
TI  - The 9-Item Patient Health Questionnaire (PHQ-9): an aid to assessment of patient
      reported functional outcomes after spinal surgery.
AB  - BACKGROUND CONTEXT: Preoperative depression is increasingly understood as an
      important predictor of patient outcomes after spinal surgery. In this study, we
      examine the relationship between depression and patient-reported functional
      outcomes (PRFOs), including disability and pain, at various time points
      postoperatively. PURPOSE: The objective of this study was to analyze the use of
      depression, as measured by the 9-Item Patient Health Questionnaire (PHQ-9), as a
      means of assessing postoperative patient-reported disability and pain. STUDY
      DESIGN/SETTING: This study includes an analysis of prospective non-randomized
      spine registry compiled through an academic multispecialty group practice model.
      PATIENT SAMPLE: A total of 1,000 spinal surgery patients from an affiliated
      surgical registry, enrolled from January 2010 onward, were included in this
      study. OUTCOME MEASURES: Pain was assessed via the visual analog scale (VAS) for
      leg or back pain. Disability was measured by the Oswestry Disability Index (ODI).
      Depression was measured by the PHQ-9. METHODS: Patient data were collected
      preoperatively and at 1, 4, 10, and 24 months postoperatively. Data were analyzed
      via analysis of variance and Pearson correlation coefficient. RESULTS: All
      patient stratifications analyzed experienced improvements in pain and ability
      postoperatively, as measured by the VAS and the ODI, respectively. Moderately and
      severely depressed patients (as measured by preoperative PHQ-9) experienced
      decreases in the mean PHQ-9 score of -6.00 and -7.96 24 months after surgery,
      respectively. CONCLUSIONS: In all groups, spinal surgery was followed by relief
      of pain and improved PRFO. Preoperative depression, as measured by the PHQ-9,
      predicted postoperative PRFO. Patients with moderate to severe depression as
      measured by the PHQ-9 experienced large mean decreases in the PHQ-9 score
      postoperatively. As a psychosocial metric, the PHQ-9 is a useful method of
      assessing value-added service of a spinal surgery.

PMID- 29366985
TI  - Impaction durability of porous polyether-ether-ketone (PEEK) and titanium-coated
      PEEK interbody fusion devices.
AB  - BACKGROUND CONTEXT: Various surface modifications, often incorporating roughened
      or porous surfaces, have recently been introduced to enhance osseointegration of
      interbody fusion devices. However, these topographical features can be vulnerable
      to damage during clinical impaction. Despite the potential negative impact of
      surface damage on clinical outcomes, current testing standards do not replicate
      clinically relevant impaction loading conditions. PURPOSE: The purpose of this
      study was to compare the impaction durability of conventional smooth polyether
      ether-ketone (PEEK) cervical interbody fusion devices with two surface-modified
      PEEK devices that feature either a porous structure or plasma-sprayed titanium
      coating. STUDY DESIGN/SETTING: A recently developed biomechanical test method was
      adapted to simulate clinically relevant impaction loading conditions during
      cervical interbody fusion procedures. METHODS: Three cervical interbody fusion
      devices were used in this study: smooth PEEK, plasma-sprayed titanium-coated
      PEEK, and porous PEEK (n=6). Following Kienle et al., devices were impacted
      between two polyurethane blocks mimicking vertebral bodies under a constant 200 N
      preload. The posterior tip of the device was placed at the entrance between the
      polyurethane blocks, and a guided 1-lb weight was impacted upon the anterior face
      with a maximum speed of 2.6 m/s to represent the strike force of a surgical
      mallet. Impacts were repeated until the device was fully impacted. Porous PEEK
      durability was assessed using micro-computed tomography (uCT) pre- and
      postimpaction. Titanium-coating coverage pre- and postimpaction was assessed
      using scanning electron microscopy (SEM) and energy dispersive X-ray
      spectroscopy. Changes to the surface roughness of smooth and titanium-coated
      devices were also evaluated. RESULTS: Porous PEEK and smooth PEEK devices showed
      minimal macroscopic signs of surface damage, whereas the titanium-coated devices
      exhibited substantial visible coating loss. Quantification of the porous PEEK
      deformation demonstrated that the porous structure maintained a high porosity
      (>65%) following impaction that would be available for bone ingrowth, and
      exhibited minimal changes to pore size and depth. SEM and energy dispersive X-ray
      spectroscopy analysis of titanium-coated devices demonstrated substantial
      titanium coating loss after impaction that was corroborated with a decrease in
      surface roughness. Smooth PEEK showed minimal signs of damage using SEM, but
      demonstrated a decrease in surface roughness. CONCLUSION: Although recent surface
      modifications to interbody fusion devices are beneficial for osseointegration,
      they may be susceptible to damage and wear during impaction. The current study
      found porous PEEK devices to show minimal damage during simulated cervical
      impaction, whereas titanium-coated PEEK devices lost substantial titanium
      coverage.

PMID- 29366986
TI  - Antithrombin levels are associated with the risk of first and recurrent arterial
      thromboembolism at a young age.
AB  - BACKGROUND AND AIMS: It is as yet unknown whether antithrombin levels are
      associated with arterial thromboembolism (ATE) at a young age. To investigate the
      association between antithrombin levels and premature and recurrent ATE, we
      performed a case-control study and a subsequent nested cohort study of premature
      coronary heart disease (CHD) patients. METHODS: In the case-control study, we
      included 571 patients who had a recent premature ATE, including CHD and ischemic
      stroke (IS), and 461 healthy controls. The association between antithrombin
      levels (dichotomized: <=median vs. >median) and ATE was investigated.
      Subsequently we studied the association between antithrombin levels and recurrent
      cardiac events, ATE or death in a nested cohort of 323 CHD patients. RESULTS: Low
      antithrombin levels (<=median, 1.04 IU/mL) are associated with an increased risk
      of ATE (OR 1.46; 95% CI:1.09-1.96), after adjustment for classical cardiovascular
      risk factors. This was observed in the subgroups of CHD patients (1.43; 1.01
      2.02) and IS patients (1.48; 1.01-2.19). CHD patients with low antithrombin
      levels had a higher risk of recurrent cardiac events (HR 2.16, 95% CI:1.07-4.38).
      Especially in women with low antithrombin levels, the risk of recurrent cardiac
      events was high (HR 5.97, 95% CI 1.31-27.13) as was the risk of recurrent ATE or
      death (HR 4.22, 95% CI 1.19-15.00). CONCLUSIONS: Individuals with relatively low
      antithrombin levels have an increased risk for ATE at a younger age. CHD patients
      with low antithrombin levels, especially women, have a higher risk of recurrent
      cardiac events.

PMID- 29366987
TI  - Toe-brachial index and exercise test can improve the exploration of peripheral
      artery disease.
AB  - BACKGROUND AND AIMS: We assumed that hand-held Doppler ultrasound (DUS) at rest
      was insufficient to assess the severity of peripheral artery disease (PAD). Toe
      pressure and transcutaneous tissue oxygen pressure were studied to prove whether
      these could identify more patients with severe lower limb ischemia; exercise was
      applied to provoke ischemia. METHODS: 120 patients with PAD and 30 volunteers
      without PAD were recruited. DUS, transcutaneous tissue oxygen pressure (tcpO2)
      and toe pressure measurements were performed at rest and after exercise. The
      differential power of these examinations for severe limb ischemia (SLI) was
      determined by receiver-operating curves (ROCs) and pattern recognition by
      independent multicategory analysis (PRIMA). RESULTS: There was an obvious
      significant difference between the patient and control groups at rest; after
      exercise; the ratio of severely impaired values (ankle-brachial index - ABI, toe
      brachial index - TBI, tcpO2 measured on index forefoot) increased significantly
      in the patient group (p < 0.05). TBI, tcpO2, ABI measured after exercise could
      differentiate SLI better than the values of these tests at rest (p < 0.001). In
      ROC analysis, the largest area under the curve (AUC) was covered by post- (AUC:
      0.860) and pre-exercise TBI (AUC: 0.785), and post-exercise tcpO2 (AUC: 0.720) (p
      < 0.001). Post-exercise TBI gained the best discriminant score in PRIMA.
      CONCLUSIONS: Pre- and post-exercise non-invasive vascular tests could reveal
      severe limb ischemia. Toe pressure measurement and TBI should become a basic part
      of the vascular workup.

PMID- 29366988
TI  - PCSK9 inhibition alters the lipidome of plasma and lipoprotein fractions.
AB  - BACKGROUND AND AIMS: While inhibition of proprotein convertase subtilisin/kexin
      type 9 (PCSK9) is known to result in dramatic lowering of LDL-cholesterol (LDL
      C), it is poorly understood how it affects other lipid species and their
      metabolism. The aim of this study was to characterize the alterations in the
      lipidome of plasma and lipoprotein particles after administration of PCSK9
      inhibiting antibody to patients with established coronary heart disease. METHODS:
      Plasma samples were obtained from patients undergoing a randomized placebo
      controlled phase II trial (EQUATOR) for the safe and effective use of RG7652, a
      fully human monoclonal antibody inhibiting PCSK9 function. Lipoprotein fractions
      were isolated by sequential density ultracentrifugation, and both plasma and
      major lipoprotein classes (VLDL-IDL, LDL, HDL) were subjected to mass
      spectrometric lipidomic profiling. RESULTS: PCSK9 inhibition significantly
      decreased plasma levels of several lipid classes, including sphingolipids
      (dihydroceramides, glucosylceramides, sphingomyelins, ceramides), cholesteryl
      esters and free cholesterol. Previously established ceramide ratios predicting
      cardiovascular mortality, or inflammation related eicosanoid lipids, were not
      altered. RG7652 treatment also affected the overall and relative distribution of
      lipids in lipoprotein classes. An overall decrease of total lipid species was
      observed in LDL and VLDL + IDL particles, while HDL-associated phospholipids
      increased. Following the treatment, LDL displayed reduced lipid cargo, whereas
      relative lipid proportions of the VLDL + IDL particles were mostly unchanged, and
      there were relatively more lipids carried in the HDL particles. CONCLUSIONS:
      Administration of PCSK9 antibody significantly alters the lipid composition of
      plasma and lipoprotein particles. These changes further shed light on the link
      between anti-PCSK9 therapies and cardiovascular risk.

PMID- 29366989
TI  - Different effects of apnea during rapid eye movement period on peripheral
      arterial stiffness in obstructive sleep apnea.
AB  - BAKGROUND AND AIMS: Obstructive sleep apnea (OSA) contributes to cardiovascular
      diseases, including arterial stiffness. The association between OSA and
      peripheral arterial stiffness indices remains controversial. METHODS: This study
      recruited 275 patients who were referred for sleep apnea study. Arterial
      stiffness was assessed by peripheral compliance index (CI) and central pulse wave
      velocity derived from digital volume pulse (PWVDVP) by photoplethysmography.
      Overnight polysomnography and autonomic nerve system function tests were also
      conducted. RESULTS: A total of 275 patients (170 men) were recruited. Most were
      middle-aged and overweight. Most patients (112/275, 40.7%) had rapid eye movement
      (REM)-predominant OSA. The CI was significantly correlated with the apnea
      hypopnea index (AHI) (R = -0.132, p = 0.029) and AHI-REM (R = -0.170, p = 0.005)
      and AHI non-REM (R = -0.122, p = 0.043). Among models and variable used to
      predict CI, only male sex (B = -0.708, p = 0.007) and AHI-REM (B = -0.010, p =
      0.033) were independent predictors of CI. An increase in the interquartile range
      of AHI-REM was associated with a 9.6% decrease in CI. CONCLUSIONS: AHI-REM was
      independently correlated with a peripheral arterial stiffness index, CI. AHI-REM
      may be a suitable surrogate marker for predicting peripheral arterial stiffness
      in OSA patients.

PMID- 29366990
TI  - Environment-wide association study to identify novel factors associated with
      peripheral arterial disease: Evidence from the National Health and Nutrition
      Examination Survey (1999-2004).
AB  - BACKGROUND AND AIMS: An environment-wide association study (EWAS) may be useful
      to comprehensively test and validate associations between environmental factors
      and peripheral arterial disease (PAD) in an unbiased manner. METHODS: Data from
      cross-sectional cohorts from the US National Health and Nutrition Examination
      Survey (1999-2004) were randomly 50:50 split into training set and testing set. A
      value of ankle-brachial index (ABI) <1.0 or >1.4 defined PAD. We performed
      multiple linear regression analyses associating each of the 417 environmental and
      self-reported factors with PAD in the training set (false discovery rate <5%).
      Significant findings were validated in the testing set (p < 0.05) and entered
      into a logistic regression model with penalized likelihood based on the Akaike
      Information Criterion (AIC). RESULTS: Overall, 6819 participants >40 years old
      were included. The validated factors comprised positive associations with smoking
      associated factors (cigarette smoker, family smoker and smoked >100 cigarettes,
      urinary cotinine), cadmium, urinary albumin, C-reactive protein, blood o-xylene
      and thyroxine 4, and inverse associations with alpha-carotene and trans-/cis-beta
      carotene for PAD. Finally, only 4 of these factors were nominally significant in
      the AIC-selected model: cadmium (OR 1.27, 95% CI 1.12-1.45), cis-beta-carotene
      (OR 0.81, 95% CI 0.72-0.91), CRP (OR 1.19, 95% CI 1.03-1.38) and urinary albumin
      (OR 1.20, 95% CI 1.04-1.38). CONCLUSIONS: Our systematic evaluation provides new
      knowledge on the complex array of environmental correlates of PAD. These
      identified correlates need to be probed in further observational and
      interventional studies.

PMID- 29366991
TI  - Comparison of cardiovascular outcomes and all-cause mortality in patients with
      chronic hepatitis B and C: A 13-year nationwide population-based study in Asia.
AB  - BACKGROUND AND AIMS: Viral hepatitis infection has been linked to increased
      atherosclerosis. We therefore investigated cardiovascular outcomes in patients
      with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. METHODS:
      Electronic medical records during 2000-2012 were retrieved from the Taiwan
      National Health Insurance Research Database. Exclusion criteria were age <18,
      history of coexisting HBV and HCV infection, acute coronary syndrome, coronary
      intervention, venous thromboembolism, peripheral artery disease, stroke, major or
      gastrointestinal bleeding, malignancy, and a follow-up period <180 days. Patients
      with HBV and HCV infection were propensity-matched then compared for outcomes.
      Primary outcomes were cardiovascular events at the 1-year follow-up, 3-year
      follow-up, 5-year follow-up, and at the end of follow-up. RESULTS: 41,554
      patients with diagnosis of HBV or HCV were retrieved from 2000 to 2012. After
      exclusion criteria, 31,943 patients were eligible for analysis and propensity
      score matched. The study population consisted of 6030 patients with HBV infection
      and 6030 patients with HCV infection. Risk of composite arterial events (acute
      coronary syndrome, peripheral artery disease, and acute ischemic stroke) was
      significantly higher in patients with HCV infection compared with patients with
      HBV infection (p = 0.012 at 5-year follow-up and p = 0.003 at the end of follow
      up). All-cause mortality was significantly higher in patients with HCV infection
      compared with patients with HBV infection (p < 0.001 at 3-year follow-up, 5-year
      follow-up, and at the end of follow-up). CONCLUSIONS: In patients with chronic
      viral hepatitis, subjects with HCV infection had a significantly higher risk of
      composite arterial events and all-cause mortality compared with those with HBV
      infection.

PMID- 29366992
TI  - Differential effects of brachial and central blood pressures on circulating
      levels of high-sensitivity cardiac troponin I in the general population.
AB  - BACKGROUND AND AIMS: Severe cardiac load increases circulating concentrations of
      high-sensitivity cardiac troponin I (hs-cTnI) through non-ischemic mechanisms.
      The present study was designed to investigate the effect of central blood
      pressure (BP), which reflects cardiac load rather than peripheral BP, on serum
      concentrations of hs-cTnI in subjects with or without increased arterial
      stiffness. METHODS: We enrolled 1210 participants taking part in a yearly health
      checkup program. Laboratory measurements included serum concentrations of hs-cTnI
      and derivative reactive oxygen metabolites (d-ROM), as well as plasma
      concentrations of B-type natriuretic peptide (BNP). Central BP and the radial
      augmentation index (rAI) were evaluated non-invasively using an automated device.
      RESULTS: Univariate and multivariable regression analysis showed that both
      brachial and central BP were significantly associated with hs-cTnI. When subjects
      were divided into two groups according to the mean rAI value, those with higher
      rAI had higher hs-cTnI concentrations than those with lower rAI. In subgroup
      analyses, in those with lower rAI, brachial but not central systolic BP was
      independently associated with hs-cTnI, whereas in those with higher rAI, central
      but not brachial systolic BP was independently associated with hs-cTnI. These
      associations remained significant after further adjustment for BNP and/or d-ROM
      concentrations. CONCLUSIONS: Circulating levels of hs-cTnI increase with
      increasing brachial and central BP, but the effect of central BP was greater in
      subjects with higher rAI. This indicates that central BP may have a strong effect
      on silent myocardial damage, assessed as increased circulating hs-cTnI,
      particularly in subjects with increased arterial stiffness.

PMID- 29366993
TI  - Circulating microRNAs identify patients at increased risk of in-stent restenosis
      after peripheral angioplasty with stent implantation.
AB  - BACKGROUND AND AIMS: Target lesion restenosis is the most frequent complication
      after angioplasty and stenting for peripheral artery disease (PAD). MicroRNAs
      (miRs) regulate crucial pathophysiological processes leading to in-stent
      restenosis and thrombosis. The aim of this study was to investigate the
      predictive value of 11 miRs for the composite endpoint of target lesion
      restenosis and atherothrombotic events (primary endpoint), and target vessel
      revascularization (TVR, secondary endpoint) in 62 consecutive PAD patients after
      infrainguinal angioplasty with stent implantation. METHODS: Circulating miRs were
      assessed using quantitative real-time polymerase chain reactions. RESULTS: Within
      the 2 years of follow-up, the primary endpoint occurred in 26 patients (41.9%),
      and 21 patients (33.9%) underwent TVR. miR-92a and miR-195 were identified as
      independent predictors of the primary endpoint after adjustment for age, sex and
      clinical risk factors with respective HR per 1 increase of standard deviation (1
      SD) of 0.55 (95% CI: 0.34-0.88, p = 0.013) and HR per 1-SD of 0.40 (95% CI: 0.23
      0.68, p = 0.001). MiR-195 independently predicted TVR with HR per 1-SD of 0.40
      (95% CI: 0.22-0.75, p = 0.005). Adding miR-195 to clinical risk factors improved
      Harrell's C-index to 0.75 (95% CI: 0.66-0.85, p = 0.03) and was superior to a
      model with miR-92a (C-index: 0.70, 95% CI: 0.60-0.80, p for comparison =0 .012).
      Assessment of both miR-92a and miR-195 had no incremental value when compared to
      miR-195 alone (C-index: 0.79, 95% CI: 0.69-0.88, p = 0.313). CONCLUSIONS:
      Circulating miR-195 predicts adverse ischemic events and TVR after infrainguinal
      angioplasty with stent implantation. MiR-195 could improve risk stratification
      after peripheral endovascular revascularizations.

PMID- 29366995
TI  - Anterior Cervical Total Disk Replacement versus Fusion.

PMID- 29366994
TI  - Coloring Technique of Magnetic Resonance Angiography for Superficial Temporal
      Artery to Middle Cerebral Artery Bypass Surgery.
AB  - OBJECTIVE: Superficial temporal artery (STA)-to-middle cerebral artery (MCA)
      bypass is an established surgical technique for achieving revascularization. It
      is important to select the proper recipient artery of the MCA. Three-dimensional
      computed tomographic angiography (3D-CTA) and conventional angiography are useful
      in the selection process but need contrast agents. The authors have designed a
      coloring MRA technique that needs no agents to visualize the recipient artery.
      Retrospective evaluation of the efficacy and limitation for selection of the
      recipient artery and decision of the place and size of the craniotomy were
      carried out. METHODS: The authors performed the coloring MRA before operation
      since January 2013. Ninety-two patients underwent STA-MCA bypass for
      atherosclerotic stenosis or occlusion of internal carotid artery (ICA), MCA with
      reference to the coloring MRA. To evaluate the efficacy of coloring MRA, the
      control group consisted of 75 patients who underwent STA-MCA bypass between
      January 2012 to November 2013 with reference to 3D-CTA. The size of craniotomy
      was retrospectively calculated and compared. RESULTS: Neither additional
      craniotomy nor wrong selection of the recipient artery was done in either group.
      There was no significant difference in size between the 2 groups in both single
      and double bypass. CONCLUSIONS: The coloring MRA technique was not inferior to 3D
      CTA with respect to the size of craniotomy. This novel technique was found to be
      very helpful not only for the virtual identification of the proper recipient
      artery but also for preoperative simulation such as decisions about length of
      donor artery, location, and size of craniotomy.

PMID- 29366996
TI  - Chronic Subdural Hematoma: So Common and So Neglected.

PMID- 29366997
TI  - Clinical and Radiologic Results of Anterior Cervical Discectomy and Fusion for
      Cervical Spondylotic Myelopathy in Elderly Patients with T2-Weighted Increased
      Signal Intensity.
AB  - OBJECTIVE: To investigate clinical and radiologic results of anterior cervical
      discectomy and fusion for cervical spondylotic myelopathy in elderly patients
      with T2-weighted increased signal intensity (ISI), focusing specifically on the
      quantitative analysis of ISI. METHODS: We retrospectively reviewed 88 patients
      with cervical spondylotic myelopathy with ISI who underwent anterior cervical
      discectomy and fusion with a minimum 1-year follow-up. Patients were divided into
      2 groups: patients older than 65 (elderly group, 36 patients) or younger (young
      group, 52 patients). The Japanese Orthopaedic Association (JOA) score was used to
      evaluate the neurologic status. The signal change ratio (SCR) was defined as the
      grayscale of ISI region divided by that at C7-T1 disc level. The C2-C7 sagittal
      alignment, range of motion, SCR, and ISI length were measured. RESULTS: There was
      no statistically significant difference between the 2 groups in C2-C7 sagittal
      alignment and range of motion. However, the JOA score at 1-year follow-up and
      recovery rate in elderly group were significantly lower than in young group (P <
      0.001). SCR and ISI length were significantly greater in elderly group than in
      young group, whereas their changes were significantly lower in elderly group (P <
      0.05). Multivariate logistic regression analysis showed that an older age, a
      lower preoperative JOA score, a greater preoperative SCR, and a longer
      preoperative ISI length at 1-year follow-up were negatively correlated with the
      clinical outcomes in the elderly group (P < 0.05). CONCLUSIONS: Compared with
      young patients with ISI, the elderly patients had a lower preoperative JOA score,
      a greater preoperative SCR, and a longer preoperative ISI length, indicating poor
      surgical outcomes.

PMID- 29366998
TI  - The Role of Neurosurgery in Countries with Limited Facilities: Facts and
      Challenges.
AB  - The Lancet Commission on Global Surgery has recently focused its attention on the
      lack of surgical care worldwide. Like other surgical subspecialties,
      neurosurgical care needs to be better distributed around the world, with a major
      focus on low- to middle-income countries. Neurosurgical diseases like
      hydrocephalus, traumatic brain injury, and brain tumors have a high impact on
      families, individual quality of life, and cost for the society. Implementation of
      neurosurgical care in poor settings is not easy. More than other surgeries,
      neurosurgery requires great amounts of human resources, dedicated environments,
      and specialized postoperative care. It is responsibility of the neurosurgical
      community to identify major areas of current gaps and outline strategies for
      intervention.

PMID- 29366999
TI  - L5 En-Bloc Vertebrectomy with Customized Reconstructive Implant: Comparison of
      Patient-Specific Versus Off-the-Shelf Implant.
AB  - BACKGROUND: Spine surgery has the potential to benefit from additive
      manufacturing/3-dimensional printing (3DP) technology with complex anatomical
      pathologies requiring reconstruction, with the potential to customize surgery to
      reduce operative times, reduce blood loss, provide immediate stability, and
      potentially improve fusion rates. We report a unique case of intraoperative trial
      placement of a custom patient-specific implant (PSI) versus the final
      implantation of a customizable off-the-shelf (OTS) implant. Data collected for
      comparison included time to implant, ease of implantation, firmness of press-fit,
      and fixation options after implantation. CASE DESCRIPTION: A 64-year-old man
      presented with low back pain. Computed tomography and magnetic resonance imaging
      revealed a solitary lesion in the L5 vertebral body, confirmed by positron
      emission tomography scan. Removal of the L5 vertebral body was performed, and
      reconstruction was achieved with an expandable cage. The time of implant
      insertion was minimal with the PSI (90 seconds) versus the OTS (>40 minutes).
      Immediate press-fit and "firmness" of implantation was clearly superior with the
      PSI, although this was an intraoperative subjective assessment. Other benefits
      include integral fixation that is predetermined with the PSI, reduced time and
      blood loss, and ease of bone grafting with a PSI. CONCLUSIONS: Use of 3DP has
      been able to reduce operative time significantly. Surgeons can train before
      performing complex procedures, which enhances their presurgical planning, with
      the goal to maximize patient outcomes. When considering implants and prostheses,
      the use of 3DP allows a superior anatomical fit for the patient, with the
      potential to improve restoration of anatomy.

PMID- 29367000
TI  - The Radiographic Effects of Surgical Approach and Use of Retractors on the Brain
      After Anterior Cranial Fossa Meningioma Resection.
AB  - OBJECTIVE: There is an increasing trend toward skull base (SB) approaches and
      retractorless surgery to minimize brain manipulation during surgery. We evaluated
      the radiographic changes over time after surgical resection of anterior cranial
      fossa meningiomas with and without both SB approaches and/or fixed retractor
      systems. METHODS: All adults undergoing primary resection of an anterior cranial
      fossa World Health Organization grade I meningioma through a craniotomy at a
      single academic tertiary-care institution from 2010 to 2015 were retrospectively
      reviewed. Magnetic resonance imaging scans were reviewed and contrast-enhanced
      tumor and fluid-attenuated inversion recovery (FLAIR) volumes were measured.
      Matched-pair analyses between patients who underwent SB and non-SB approaches, as
      well as retractorless and retractor-assisted (RA) surgery, were made. RESULTS: Of
      the 136 total patients, 20 (15%), 12 (9%), 46 (34%), and 58 (43%) underwent
      SB/retractorless, SB/RA, non-SB/retractorless, and non-SB/RA surgery,
      respectively. Patients who underwent non-SB and RA surgery each independently had
      longer times to FLAIR resolution than those who underwent SB (20.9 vs. 5 months;
      P = 0.04) and retractorless (12 vs. 5.2 months; P = 0.02) surgery, respectively.
      Patients who underwent both non-SB and RA surgery had the longest median time to
      FLAIR resolution (30 months vs. 4 months in SB/retractorless, 3.6 months in
      SB/RA, and 3 months in non-SB/retractorless; P < 0.05). CONCLUSIONS: The use of
      SB approaches in combination with retractorless surgery may decrease the duration
      needed for FLAIR resolution after surgery. The results from this study therefore
      advocate SB approaches and retractorless surgery along the anterior SB when
      possible.

PMID- 29367001
TI  - Comparison Between Posterior Lumbar Interbody Fusion and Transforaminal Lumbar
      Interbody Fusion for the Treatment of Lumbar Degenerative Diseases: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVE: To compare the efficacy and safety in the management of lumbar
      diseases performed by either posterior lumbar interbody fusion (PLIF) or
      transforaminal lumbar interbody fusion (TLIF). Interbody fusion is considered the
      "gold standard" in the treatment of lumbar degenerative diseases. Both PLIF and
      TLIF have been advocated, and it remains controversial as to the best operative
      technique. METHODS: The electronic databases including Embase, PubMed, and
      Cochrane library were searched to identify relevant studies up to September 2017.
      The primary outcomes were fusion rate, complications, and clinical satisfaction.
      The secondary outcomes were length of hospitalization, operation time, blood
      loss, postoperative visual analog scale, Oswestry Disability Index, and Japanese
      Orthopaedic Association Score. Data analysis was conducted with RevMan 5.3
      software. RESULTS: A total of 16 studies involving 1502 patients (805 patients in
      PLIF group and 697 in TLIF group) were included in the meta-analysis. The pooled
      analysis showed that there was no significant difference in terms of fusion rate
      (P > 0.05) and clinical satisfaction (P > 0.05) between the 2 groups. TLIF was
      superior to PLIF with significantly lower incidence of nerve root injury (P <
      0.05) and dural tear (P < 0.05). However, there was no significant difference
      regarding wound infection (P > 0.05) and graft malposition (P > 0.05). PLIF
      required significant longer operation time (P < 0.05) and was associated with
      more blood loss (P < 0.05). Although TLIF was associated with better
      postoperative visual analog scale, Oswestry Disability Index, and Japanese
      Orthopaedic Association Score than PLIF, there was no statistical difference
      regarding these results. CONCLUSIONS: The available evidence suggests that both
      TLIF and PLIF could achieve similar clinical satisfaction and fusion rate in the
      management of degenerative lumbar diseases. However, TLIF was superior to PLIF
      with shorter operation time, less blood loss, and lower incidence of nerve root
      injury and dural tear. There is no significant difference between both groups
      regarding wound infection and graft malposition.

PMID- 29367002
TI  - The worrying mind in control: An investigation of adaptive working memory
      training and cognitive bias modification in worry-prone individuals.
AB  - Worry refers to the experience of uncontrollable negative thoughts. Cognitive
      models suggest that the combination of negative information processing biases
      along with diminished attentional control contribute to worry. In the current
      study we investigate whether promoting a) adaptive interpretation bias and b)
      efficient deployment of attentional control would influence the tendency to
      worry. Worry-prone individuals (n = 60) received either active cognitive bias
      modification for interpretation bias (CBM-I) combined with sham working memory
      training (WMT), adaptive WMT combined with sham CBM-I, or sham WMT combined with
      sham CBM-I. Neither of the active training conditions reduced worry during a
      breathing focus task relative to the control condition. However, when considering
      inter-individual differences in training-related improvements, we observed a
      relation between increases in positive interpretation bias and a decrease in
      negative intrusions. Moreover, increases in working memory performance were
      related to a reduction in reactivity of negative intrusions to a worry period.
      Our findings show that facilitating a more benign interpretation bias and
      improving working memory capacity can have beneficial effects in terms of worry,
      but also highlight that transfer related gains from existing training procedures
      can be dependent upon improvement levels on the training task.

PMID- 29367003
TI  - Hsp90 inhibition renders iNOS aggregation and the clearance of iNOS aggregates by
      proteasomes requires SPSB2.
AB  - Inducible nitric oxide synthase (iNOS) plays important roles in cell injury and
      host defense. Our early study demonstrated that heat shock protein 90 (Hsp90)
      interacts with iNOS and this interaction enhances iNOS function. Recently, we
      reported that Hsp90 is also essential for iNOS gene transactivation. In the
      present study, we investigate the role of Hsp90 in controlling iNOS protein
      stability. In mouse macrophages, Hsp90 inhibition dissociated Hsp90 from iNOS and
      the latter subsequently formed aggregates. Aggregation deactivated iNOS. iNOS
      aggregates were cleared by the ubiquitin-proteasome system (UPS) inside cells.
      CHIP, an Hsp90-dependent E3 ligase, was previously implicated in iNOS turnover.
      However, CHIP knockdown had little effect on iNOS degradation in Hsp90-inhibited
      cells, indicating that other E3 ligases accounted for the clearance of iNOS
      aggregates. Further studies revealed that the SPRY domain-containing SOCS box
      protein 2 (SPSB2), an E3 ligase-recruiting protein, was essential for the
      ubiquitination of iNOS aggregates. SPSB2 knockdown or deleting the SPSB2
      interacting domain on iNOS prevented the clearance of iNOS aggregates in Hsp90
      inhibited cells. Thus, besides modulating iNOS function and gene transcription,
      Hsp90 is also essential for the protein stability of iNOS. Hsp90 blockade induces
      iNOS aggregation and SPSB2 is required for UPS degradation of iNOS aggregates.

PMID- 29367004
TI  - Modulation of systemic and mucosal immune responses of Catla catla (Hamilton,
      1822) experimentally challenged with gill monogeneans.
AB  - The present study investigated the modulation of systemic and mucosal immunity of
      catla (Catla catla) experimentally challenged with gill monogeneans. Fingerlings
      of catla (24.2 +/- 1.5 g) without any parasites were randomly distributed into
      two groups each comprising quadruplicate tanks (10 fish per tank). The fish in
      the infected group were challenged with gill monogeneans by cohabitation method.
      The control group fish were not exposed to parasites. Serum and mucus were
      collected from both control and infected fish and different immunological
      parameters were measured at weekly interval for four weeks. Monogeneans on the
      fish gills were also quantified from infected fish at weekly interval. Different
      systemic immunological parameters viz. myeloperoxidase content, alkaline
      phosphatase and hemolytic activity of serum showed a significant increase (p <
      .05) in infected group. However, respiratory burst activity, total serum protein
      and anti-protease activity did not show any significant enhancement (p < .05) in
      infected group compared to control. In case of mucosal parameters,
      myeloperoxidase content, alkaline phosphatase activity, total protein content and
      anti-protease activity of mucus showed significant enhancement (p < .05) in
      infected group compared to control. Parasite prevalence was 100% in the infected
      group in all the sampling weeks. The mean intensity of parasites was
      progressively increased and the highest number of monogeneans per gill (45 +/-
      4.56) was observed during 4th week post challenge. Control group had mean
      intensity and prevalence of zero. In conclusion, there was the participation of
      immune system components against monogenean infection in catla. However, the
      progressive increase in monogenean intensity indicates some immune evasion
      mechanism available with the monogenean to co-exist with the host in the face of
      host's immune responses.

PMID- 29367005
TI  - The impaired immune function and structural integrity by dietary iron deficiency
      or excess in gill of fish after infection with Flavobacterium columnare:
      Regulation of NF-kappaB, TOR, JNK, p38MAPK, Nrf2 and MLCK signalling.
AB  - The aim of this study was to investigate the effects and potential mechanisms of
      dietary iron on immune function and structural integrity in gill of young grass
      carp (Ctenopharyngodon idella). A total of 630 grass carp (242.32 +/- 0.58 g)
      were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38,
      63.47, 86.43, 111.09, 136.37 and 73.50 mg/kg for 60 days. Subsequently, a
      challenge test was conducted by infection with Flavobacterium columnare to
      investigate the effects of dietary iron on gill immune function and structural
      integrity in young grass carp. First, the results indicated that compared with
      the optimal iron level, iron deficiency decreased lysozyme (LZ) and acid
      phosphatase (ACP) activities, complement 3 (C3), C4 and immunoglobulin M (IgM)
      contents, and down-regulated the mRNA levels of antibacterial peptides, anti
      inflammatory cytokines (except IL-4/13B), inhibitor of kappaBalpha
      (IkappaBalpha), target of rapamycin (TOR) and ribosomal protein S6 kinase 1
      (S6K1). In contrast, iron deficiency up-regulated the mRNA levels of pro
      inflammatory cytokines (except IL-6 and IFN-gamma2), nuclear factor kappaB p65
      (NF-kappaBp65), IkappaB kinases alpha (IKK), IKKbeta, IKKgamma, eIF4E-binding
      protein 1 (4E-BP1) and 4E-BP2 in gill of young grass carp, indicating that iron
      deficiency could impair immune function in fish gill. Second, iron deficiency
      down-regulated the mRNA levels of inhibitor of apoptosis protein (IAP) and
      myeloid cell leukemia 1 (Mcl-1), decreased activities and mRNA levels of
      antioxidant enzymes, down-regulated the mRNA levels of NF-E2-related factor 2
      (Nrf2) and tight junction proteins (except claudin-12 and -15), and
      simultaneously increased malondialdehyde (MDA), protein carbonyl (PC) and
      reactive oxygen species (ROS) contents. Iron deficiency also up-regulated mRNA
      levels of cysteinyl aspartic acid-protease (caspase) -2, -7, -8, -9, Fas ligand
      (FasL), apoptotic protease activating factor-1 (Apaf-1), B-cell-lymphoma-2
      associated X protein (Bax), p38 mitogen-activated protein kinase (p38MAPK), Kelch
      like ECH-associating protein (Keap) 1a, Keap1b, claudin-12, -15 and MLCK,
      indicating that iron deficiency could disturb the structural integrity of gill in
      fish. Third, iron excess impaired immune function and structural integrity in
      gill of young grass carp. Forth, there was a better effect of ferrous fumarate
      than ferrous sulfate in young grass carp. Finally, the iron requirements based on
      ability against gill rot, ACP activity and MDA content in gill of young grass
      carp were estimated to be 76.52, 80.43 and 83.17 mg/kg, respectively.

PMID- 29367006
TI  - Molecular characterization and functional activity of CXCL8_L3 in large yellow
      croaker Larimichthys crocea.
AB  - CXCL8, also called interleukin-8, is a typical CXC chemokine that plays a key
      role in promoting inflammation. Phylogenetically, fish CXCL8 chemokines can be
      divided into three subgroups, CXCL8_L1, CXCL8_L2, and CXCL8_L3, of which CXCL8_L3
      is a new subgroup. The CXCL8_L3 gene sequences have been reported in many fish
      species, but their function remains unknown. Here, a CXCL8_L3 (LycCXCL8_L3) gene
      was cloned from large yellow croaker Larimichthys crocea. Its open reading frame
      (ORF) was 309 nucleotides long, encoding a peptide of 102 amino acids. The
      deduced LycCXCL8_L3 protein contains an 18-aa signal peptide and an 84-aa mature
      polypeptide, which has four conserved cysteine residues (C30, C32, C57, and C73)
      as found in other known CXCL8 chemokines. Phylogenetic analysis showed
      LycCXCL8_L3 formed a major clade with CXCL8_L3 sequences from other fish species.
      The LycCXCL8_L3 transcript was constitutively expressed in all examined tissues
      and significantly up-regulated in the spleen and head kidney tissues by
      inactivated trivalent bacterial vaccine. The LycCXCL8_L3 transcript was also
      detected in peripheral blood leukocytes (PBLs), primary head kidney macrophages
      (PKM), and large yellow croaker head kidney cell line (LYCK), with the highest
      levels in PKM. Recombinant LycCXCL8_L3 (rLycCXCL8_L3) protein could not only
      chemotactically attract lymphocytes and eosinophils in PBLs, but also enhance the
      respiratory burst activity of PKM. These results indicate that LycCXCL8_L3 may
      play an important role in the inflammatory response of large yellow croaker. To
      our knowledge, this is the first report on functional study of the CXCL8_L3 in
      fish.

PMID- 29367007
TI  - An electrochemical biosensor for microRNA-196a detection based on cyclic
      enzymatic signal amplification and template-free DNA extension reaction with the
      adsorption of methylene blue.
AB  - A simple and sensitive electrochemical biosensor was developed for microRNA-196a
      detection, which is of important diagnostic significance for pancreatic cancer.
      It was based on cyclic enzymatic signal amplification (CESA) and template-free
      DNA extension reaction. In the presence of microRNA-196a, duplex-specific
      nuclease (DSN) catalyzed the digestion of the 3'-PO4 terminated capture probe
      (CP), resulting in the target recycling amplification. Meanwhile, the 3'-OH
      terminal of CP was exposed. Then, template-free DNA extension reaction was
      triggered by terminal deoxynucleotidyl transferase (TdT), producing amounts of
      single-stranded DNA (ssDNA). After ssDNA absorbed numerous methylene blue (MB),
      an ultrasensitive electrochemical readout was obtained. Based on this dual
      amplification mechanism, the proposed biosensor exhibited a high sensitivity for
      detection of microRNA-196a down to 15 aM with a linear range from 0.05 fM to 50
      pM. This biosensor displayed high specificity, which could discriminate target
      microRNAs from one base mismatched microRNAs. It also showed good reproducibility
      and stability. Furthermore, it was successfully applied to the determination of
      microRNA-196a in plasma samples. In conclusion, with the excellent analytical
      performance, this biosensor might have the potential for application in clinical
      diagnostics of pancreatic cancer.

PMID- 29367008
TI  - High-performance electrochemical sensing of circulating tumor DNA in peripheral
      blood based on poly-xanthurenic acid functionalized MoS2 nanosheets.
AB  - A high-performance sensing platform based on poly-xanthurenic acid (PXA) film
      functionalized MoS2 nanosheets was developed for electrochemical detection of
      circulating tumor DNA in peripheral blood. The MoS2 nanosheets were obtained
      using a simple ultrasonic method from bulk MoS2. The physical adsorption between
      MoS2 and aromatic XA monomers effectively improved the electropolymerization
      efficiency, accompanied with an increased electrochemical response of PXA. The
      obtained PXA/MoS2 nanocomposite not only served as a substrate for DNA
      immobilization but also reflected the electrochemical transduction originating
      from DNA immobilization and hybridization without any complex labelling processes
      or outer indicators. The immobilization of the probe ssDNA was achieved via
      noncovalent assembly due to the pi-pi interaction between PXA and DNA bases.
      After the hybridization of the probe ssDNA with the target DNA, the formation of
      helix structure induced the resulted dsDNA to be released from the surface of the
      PXA/MoS2 nanocomposite. The detection limit of this constructed DNA biosensor was
      calculated in the linear target DNA concentrations range from 1.0 * 10-16 mol/L
      to 1.0 * 10-10 mol/L and it was found to be 1.8 * 10-17 mol/L.

PMID- 29367010
TI  - Chronic minocycline treatment improves hippocampal neuronal structure, NMDA
      receptor function, and memory processing in Fmr1 knockout mice.
AB  - Fragile X Syndrome (FXS) is the most common inherited cause of intellectual
      disability, and is the leading known single-gene cause of autism spectrum
      disorder. FXS patients display varied behavioural deficits that include mild to
      severe cognitive impairments in addition to mood disorders. Currently there is no
      cure for this condition, however minocycline is becoming commonly prescribed as a
      treatment for FXS patients. Minocycline has been reported to alleviate social
      behavioural deficits, and improve verbal functioning in patients with FXS;
      however, its mode of action is not well understood. Previously we have shown that
      FXS results in learning impairments that involve deficits in N-methyl-d-aspartate
      (NMDA) receptor-dependent synaptic plasticity in the hippocampal dentate gyrus
      (DG). Here we tested whether chronic treatment with minocycline can improve these
      deficits by enhancing NMDA receptor-dependent functional and structural
      plasticity in the DG. Minocycline treatment resulted in a significant enhancement
      in NMDA receptor function in the dentate granule cells. This was accompanied by
      an increase in PSD-95 and GluN2A and GluN2B subunits in hippocampal
      synaptoneurosome fractions. Minocycline treatment also enhanced dentate granule
      cell dendritic length and branching. In addition, our results show that chronic
      minocycline treatment can rescue performance in novel object recognition in FXS
      mice. These findings indicate that minocycline treatment has both structural and
      functional benefits for hippocampal cells, which may partly contribute to the pro
      cognitive effects minocycline appears to have for treating FXS.

PMID- 29367009
TI  - Changes in resting-state functional connectivity after stroke in a mouse brain
      lacking extracellular matrix components.
AB  - In the brain, focal ischemia results in a local region of cell death and
      disruption of both local and remote functional neuronal networks. Tissue
      reorganization following stroke can be limited by factors such as extracellular
      matrix (ECM) molecules that prevent neuronal growth and synaptic plasticity. The
      brain's ECM plays a crucial role in network formation, development, and
      regeneration of the central nervous system. Further, the ECM is essential for
      proper white matter tract development and for the formation of structures called
      perineuronal nets (PNNs). PNNs mainly surround parvalbumin/GABA inhibitory
      interneurons, of importance for processing sensory information. Previous studies
      have shown that downregulating PNNs after stroke reduces the neurite-inhibitory
      environment, reactivates plasticity, and promotes functional recovery. Resting
      state functional connectivity (RS-FC) within and across hemispheres has been
      shown to correlate with behavioral recovery after stroke. However, the
      relationship between PNNs and RS-FC has not been examined. Here we studied a
      quadruple knock-out mouse (Q4) that lacks four ECM components: brevican,
      neurocan, tenascin-C and tenascin-R. We applied functional connectivity optical
      intrinsic signal (fcOIS) imaging in Q4 mice and wild-type (129S1 mice) before and
      14 days after photothrombotic stroke (PT) to understand how the lack of crucial
      ECM components affects neuronal networks and functional recovery after stroke.
      Limb-placement ability was evaluated at 2, 7 and 14 days of recovery through the
      paw-placement test. Q4 mice exhibited significantly impaired homotopic RS-FC
      compared to wild-type mice, especially in the sensory and parietal regions.
      Changes in RS-FC were significantly correlated with the number of
      interhemispheric callosal crossings in those same regions. PT caused unilateral
      damage to the sensorimotor cortex and deficits of tactile-proprioceptive placing
      ability in contralesional fore- and hindlimbs, but the two experimental groups
      did not present significant differences in infarct size. Two weeks after PT, a
      general down-scaling of regional RS-FC as well as the number of regional
      functional connections was visible for all cortical regions and most notable in
      the somatosensory areas of both Q4 and wild-type mice. Q4 mice exhibited higher
      intrahemispheric RS-FC in contralesional sensory and motor cortices compared to
      control mice. We propose that the lack of growth inhibiting ECM components in the
      Q4 mice potentially worsen behavioral outcome in the early phase after stroke,
      but subsequently facilitates modulation of contralesional RS-FC which is relevant
      for recovery of sensory motor function. We conclude that Q4 mice represent a
      valuable model to study how the elimination of ECM genes compromises neuronal
      function and plasticity mechanisms after stroke.

PMID- 29367011
TI  - Longitudinal injecting risk behaviours among people with a history of injecting
      drug use in an Australian prison setting: The HITS-p study.
AB  - BACKGROUND: HCV transmission remains high in prisons globally. Understanding
      injecting risk behaviours in prisons is crucial to effectively develop and
      implement HCV prevention programs in this setting including treatment as
      prevention. METHODS: HITS-p is a cohort study which enrolled people with a
      history of injecting drug use in prisons in NSW, Australia from 2005 to 2013.
      Participants completed an interview at enrolment and follow-up visits to
      determine injecting behaviours. Generalized estimating equation (GEE) and
      logistic regression methods were used to assess injecting risk behaviours prior
      to and following prison entry and to investigate injecting risk behaviours in
      prison. RESULTS: Overall, 499 participants with a history of injecting drug use
      were included (median age, 26 years; 65% male). Participants were significantly
      less likely to inject drugs following incarceration. Among injectors,
      participants were less likely to inject >=weekly but more likely to share a
      needle/syringe. At enrolment, the proportion reporting any injecting, >=weekly
      injecting, and needle/syringe sharing in prison was highest among younger
      individuals. Younger age was associated with both re-initiation and continuation
      of injecting drug use following prison entry. Among those continuously
      imprisoned, younger age was associated with increased odds of any injecting,
      >=weekly injecting, and sharing a needle/syringe. CONCLUSIONS: Upon entry to
      prison, injecting drug use decreased but syringe sharing increased among
      injectors. Younger individuals are most likely to exhibit high-risk injecting
      behaviours in prison. These data highlight the need for improved HCV prevention
      strategies (including improved needle/syringe access and scale up of HCV therapy)
      for those at increased risk of HCV transmission in prison, including younger
      individuals.

PMID- 29367012
TI  - Consumer agency in cannabis supply - Exploring auto-regulatory documents of the
      cannabis social clubs in Spain.
AB  - BACKGROUND: There is growing experience with the not-for-profit, consumer-driven
      cannabis social club (CSC) model that builds on self-supply, self-organization
      and harm-reduction; these are principles upon which people who use drugs (PWUD)
      have been engaging for decades. Recent legalization of cannabis in a number of
      jurisdictions and the related challenges in regulating production, sale, taxation
      and health-related matters have raised interest in non-commercial models of
      cannabis supply. The "codes of conduct" (CsoC) of CSC federations in Spain might
      reveal whether a consumer-based model could overcome these challenges. METHODS:
      To examine the content of the CSC auto-regulatory documents, an online search
      using key terms to identify the CsoC was conducted. Six documents were found;
      analysis of the main thematic categories and overarching themes was conducted. It
      was discussed how these corresponded to the areas of cannabis policy regulation
      and what the main limitations of the CSC model were. RESULTS: The CsoC detailed
      the rules for CSC administration, not-for-profit aims, "invitation only" and
      other conditions of membership, collective cultivation and security as well as
      for operation of the consumption venue and health-related initiatives. The themes
      in the CsoC overlapped with cannabis regulatory areas as outlined
      internationally. Concern over cannabis prices and potency was missing in the
      CsoC. The potential strengths of the CSC model might include safe environment for
      peer-delivered harm reduction practice, preventing illicit transactions, quality
      control, shifting economic surplus to the consumers and increased consumer
      responsibility. The limitations of the CSC model include high threshold,
      disguised motives, tax revenue and the risk of both under- and over-regulation.
      CONCLUSION: CSCs represent an opportunity to enhance consumer agency and
      responsibility. The right "to be self-supplied" with psychoactive substances can
      be granted to consumer associations - but authorities need to provide a framework
      to facilitate this voluntary self-organization, including minimum standards
      around public health and safety, and to involve consumers in the development of
      these regulations.

PMID- 29367013
TI  - Evaluating the use of whole-genome sequencing for outbreak investigations in the
      lack of closely related reference genome.
AB  - Whole-genome sequencing (WGS) has emerged as a powerful molecular typing method
      for outbreak analysis enabling the rapid discrimination between outbreak and non
      outbreak isolates. However, such analysis can be challenging in the absence of
      closely related reference genomes. In this study, we assessed the use of WGS in
      investigating an outbreak of a relatively understudied bacterial pathogen with no
      publicly available closely related reference genome. Eleven Burkholderia cepacia
      complex (Bcc) isolates (seven from patients and four from disposable dermal
      gloves packages) that were collected during an outbreak were sequenced using the
      Illumina MiSeq platform. Our results showed that mapping the 11 sequenced Bcc
      outbreak isolates against a genetically distant reference genome yield loses
      coverage (31.6-48.3%) and a high number of detected false single-nucleotide
      polymorphisms (SNPs) (1123-2139). Therefore, a reference genome consensus from an
      outbreak clinical isolate was generated by combining both de novo assembly and
      mapping approaches. Based on this approach, we were able to demonstrate that the
      Bcc outbreak isolates were closely related and were phylogenetically distinct
      from the 11 publically available Bcc genomes. In addition, the pairwise SNP
      distance analysis detected only 1 to 6 SNPs differences among the outbreak
      isolates, confirming that contaminated disposable dermal gloves were the cause of
      the outbreak.

PMID- 29367015
TI  - An early-flowering einkorn wheat mutant with deletions of PHYTOCLOCK 1/LUX
      ARRHYTHMO and VERNALIZATION 2 exhibits a high level of VERNALIZATION 1 expression
      induced by vernalization.
AB  - Using heavy-ion beam mutagenesis of Triticum monococcum strain KU104-1, we
      identified a mutant that shows extra early-flowering; it was named extra early
      flowering 3 (exe3). Here, we carried out expression analyses of clock-related
      genes, clock downstream genes and photoperiod pathway genes, and found that the
      clock component gene PHYTOCLOCK 1/LUX ARRHYTHMO (PCL1/LUX) was not expressed in
      exe3 mutant plants. A PCR analysis of DNA markers indicated that the exe3 mutant
      had a deletion of wheat PCL1/LUX (WPCL1), and that the WPCL1 deletion was
      correlated with the mutant phenotype in the segregation line. We confirmed that
      the original strain KU104-1 carried a mutation that produced a null allele of a
      flowering repressor gene VERNALIZATION 2 (VRN2). As a result, the exe3 mutant has
      both WPCL1 and VRN2 loss-of-function mutations. Analysis of plant development in
      a growth chamber showed that vernalization treatment accelerated flowering time
      in the exe3 mutant under short day (SD) as well as long day (LD) conditions, and
      the early-flowering phenotype was correlated with the earlier up-regulation of
      VRN1. The deletion of WPCL1 affects the SD-specific expression patterns of some
      clock-related genes, clock downstream genes and photoperiod pathway genes,
      suggesting that the exe3 mutant causes a disordered SD response. The present
      study indicates that VRN1 expression is associated with the biological clock and
      the VRN1 up-regulation is not influenced by the presence or absence of VRN2.

PMID- 29367016
TI  - Visually-naive chicks prefer agents that move as if constrained by a bilateral
      body-plan.
AB  - From the first hours of life, the prompt detection of animate agents allows
      identification of biologically relevant entities. The motion of most animate
      agents is constrained by their bilaterally-symmetrical body-plan, and
      consequently tends to be aligned with the main body-axis. Thus parallelism
      between the main axis of a moving object and its motion trajectory can signal the
      presence of animate agents. Here we demonstrated that visually-naive newborn
      chicks (Gallus gallus domesticus) are attracted to objects displaying such
      parallelism, and thus show preference for the same type of motion patterns that
      elicit perception of animacy in humans. This is the first demonstration of a
      newborn non-human animal's social preference for a visual cue related to the
      constraints imposed on behaviour by bilaterian morphology. Chicks also showed
      preference for rotational movements - a potential manifestation of self
      propulsion. Results are discussed in relation to the mechanisms of animacy and
      agency detection in newborn organisms.

PMID- 29367017
TI  - Do enhanced states exist? Boosting cognitive capacities through an action video
      game.
AB  - This research reports the existence of enhanced cognitive states in which
      dramatic temporary improvements in temporal and spatial aspects of attention were
      exhibited by participants who played (but not by those who merely observed)
      action video-games meeting certain criteria. Specifically, Experiments 1 and 2
      demonstrate that the attentional improvements were exhibited only by participants
      whose skills matched the difficulty level of the video game. Experiment 2 showed
      that arousal (as reflected by the reduction in parasympathetic activity and
      increase in sympathetic activity) is a critical physiological condition for
      enhanced cognitive states and corresponding attentional enhancements. Experiment
      3 showed that the cognitive enhancements were transient, and were no longer
      observed after 30 min of rest following video-gaming. Moreover, the results
      suggest that the enhancements were specific to tasks requiring visual-spatial
      focused attention, but not distribution of spatial attention as has been reported
      to improve significantly and durably as a result of long-term video-game playing.
      Overall, the results suggest that the observed enhancements cannot be simply due
      to the activity of video-gaming per se, but might rather represent an enhanced
      cognitive state resulting from specific conditions (heightened arousal in
      combination with active engagement and optimal challenge), resonant with what has
      been described in previous phenomenological literature as "flow"
      (Csikszentmihalyi, 1975) or "peak experiences" (Maslov, 1962). The findings
      provide empirical evidence for the existence of the enhanced cognitive states and
      suggest possibilities for consciously accessing latent resources of our brain to
      temporarily boost our cognitive capacities upon demand.

PMID- 29367014
TI  - Internal validation of STRmixTM - A multi laboratory response to PCAST.
AB  - We report a large compilation of the internal validations of the probabilistic
      genotyping software STRmixTM. Thirty one laboratories contributed data resulting
      in 2825 mixtures comprising three to six donors and a wide range of multiplex,
      equipment, mixture proportions and templates. Previously reported trends in the
      LR were confirmed including less discriminatory LRs occurring both for donors and
      non-donors at low template (for the donor in question) and at high contributor
      number. We were unable to isolate an effect of allelic sharing. Any apparent
      effect appears to be largely confounded with increased contributor number.

PMID- 29367018
TI  - A new composite consisting of electrosynthesized conducting polymers, graphene
      sheets and biosynthesized gold nanoparticles for biosensing acute lymphoblastic
      leukemia.
AB  - In this work we report the synthesis of a stable composite with excellent
      electrical properties, on the surface of a biosensor. Conductive polymers offer
      both high electrical conductivity and mechanical strength. Many reports have
      focused on synthesizing conductive polymers with the aid of high-cost enzymes. In
      the current work we introduce a novel electrochemical, one-step, facile and cost
      effective procedure for synthesizing poly (catechol), without using expensive
      enzymes. The poly (catechol) conductivity was enhanced by modification with
      graphene sheets and biosynthesized gold nanoparticles. Four different robust
      methods, DPV, EIS, CV and chronoamperometry, were used to monitor the biosensor
      modifications. The peak currents of the catechol (an electroactive probe) were
      linearly related to the logarithm of the concentrations of target DNA in the
      range 100.0 MUM to 10.0 pM, with a detection limit of 1.0 pM for the DNA strand.
      The current work investigates a new, stable composite consisting of conductive
      polymers and nanoparticles, which was applied to the detection of acute
      lymphoblastic leukemia.

PMID- 29367019
TI  - Enrichment culture of electroactive microorganisms with high magnetic
      susceptibility enhances the performance of microbial fuel cells.
AB  - Many electroactive microorganisms (EAMs) are known as dissimilatory iron-reducing
      bacteria (DIRB) which can access iron as an electron acceptor to transfer
      electrons during the process of respiration. Previous research has shown that
      magnetic susceptibility (chilf) could be used as an indicator of DIRB activities.
      However, the relationship between chilf and electroactivity of EAMs is still
      unclear. Here, we report that after sediments of the Sha River enriched with
      amorphous iron, the chilf of enrichment cultures increased dramatically. The
      reactor inoculated with higher chilf enrichment cultures started earlier and had
      a higher peak voltage (0.228 V), higher power density (310.14 mW m-2) and higher
      coulombic efficiency (10.16%) than lower chilf cultures. Sequencing of bacterial
      16S rRNA gene amplicons and chilf measurement revealed that relative abundance of
      dominant phyla Proteobacteria increased with chilf values in sediments. Further
      analysis of cyclic voltammetry curves and bacterial terminal-restriction fragment
      length polymorphism (T-RFLP) of bacterial rRNA genes indicated that the improved
      performance of the MFCs might be due to a highly electroactive microbial
      community that the 162 bp terminal restriction fragments (TRFs) originated from.
      Our results suggested a potential correlation between chilf and presence of EAM
      indicating a promising route for fast screening in complex environments.

PMID- 29367020
TI  - Screening for Behavioral Risk Factors Is Not Enough to Improve Preventive
      Services Delivery.
AB  - OBJECTIVE: Unhealthy behaviors are a major cause of chronic disease.
      Preappointment screening has been suggested as one way to improve preventive care
      delivery related to these behaviors by specifying risks to be addressed. We aimed
      to determine whether screening for health-related behaviors before the clinical
      encounter will lead to higher counseling rate and service delivery by clinicians.
      METHODS: We used a pre/post design in one practice with a control practice to
      evaluate the effects of preappointment screening for 3 behavioral risk factors
      (tobacco smoke exposure, no recent dental care visit, and consumption of sugar
      sweetened beverages). After their clinic visit, we asked English-speaking parents
      whose child had one or more risk factor whether they had received counseling or
      services from their pediatrician to address them. RESULTS: We recruited 264
      parents in the pre phase and 242 in the post phase. Among 215 parents whose child
      had one or more risk factors, parents in the post phase were as likely to report
      receiving counseling than parents in the pre phase for each of the risk factors:
      smoking odds ratio 6.75 (95% confidence interval, 0.51, 88.88), dental health
      odds ratio 1.44 (95% confidence interval, 0.47, 4.41), and sugar-sweetened
      beverage consumption odds ratio 0.34 (95% confidence interval, 0.23, 5.18).
      Service delivery and reported behavior change were also similar in both phases.
      CONCLUSIONS: Counseling rates for tobacco, dental health, or sugar-sweetened
      beverage consumption were low in pediatric primary care, and preappointment
      screening did not significantly affect clinician counseling. Future efforts will
      require a more robust approach to effect change in counseling, provision of
      service, and family behavior.

PMID- 29367021
TI  - Disentangling overlapping high-field EPR spectra of organic radicals:
      Identification of light-induced polarons in the record fullerene-free solar cell
      blend PBDB-T:ITIC.
AB  - We present a combined high-field EPR and DFT study of light-induced radicals in
      the bulk heterojunction blend of PBDB-T:ITIC, currently one of the highest
      efficiency non-fullerene donor:acceptor combinations in organic photovoltaics. We
      demonstrate two different approaches for disentangling the strongly overlapping
      high-field EPR spectra of the positive and negative polarons after charge
      separation: (1) relaxation-filtered field-swept EPR based on the difference in T1
      spin-relaxation times and (2) field-swept EDNMR-induced EPR by exploiting the
      presence of 14N hyperfine couplings in only one of the radical species, the small
      molecule acceptor radical. The approach is validated by light-induced EPR spectra
      on related blends and the spectral assignment is underpinned by DFT computations.
      The broader applicability of the spectral disentangling methods is discussed.

PMID- 29367022
TI  - Sensing of heavy metal ions by intrinsic TMV coat protein fluorescence.
AB  - We propose the use of a cysteine mutant of TMV coat protein as a signal
      transducer for the selective sensing and quantification of the heavy metal ions,
      Cd2+, Pb2+, Zn2+ and Ni2+ based on intrinsic tryptophan quenching. TMV coat
      protein is inexpensive, can be mass-produced since it is expressed and extracted
      from E-coli. It also displays several different functional groups, enabling a
      wide repertoire of bioconjugation chemistries; thus it can be easily integrated
      into functional devices. In addition, TMV-ion interactions have been widely
      reported and utilized for metallization to generate organic-inorganic hybrid
      composite novel materials. Building on these previous observations, we herein
      determine, for the first time, the TMV-ion binding constants assuming the static
      fluorescence quenching model. We also show that by comparing TMV-ion interactions
      between native and denatured coat protein, we can distinguish between chemically
      similar heavy metal ions such as cadmium and zinc ions.

PMID- 29367023
TI  - Advantages of infrared transflection micro spectroscopy and paraffin-embedded
      sample preparation for biological studies.
AB  - Fourier-Transform Infrared micro-spectroscopy is an excellent method for
      biological analyses. In this paper, series metal coating films on ITO glass were
      prepared by the electrochemical method and the different thicknesses of paraffin
      embedding rat's brain tissue on the substrates were studied by IR micro
      spetroscopy in attenuated total reflection (ATR) mode and transflection mode
      respectively. The Co-Ni-Cu alloy coating film with low cost is good reflection
      substrates for the IR analysis. The infrared microscopic transflection mode needs
      not to touch the sample at all and can get the IR spectra with higher signal to
      noise ratios. The Paraffin-embedding method allows tissues to be stored for a
      long time for re-analysis to ensure the traceability of the sample. Also it
      isolates the sample from the metal and avoids the interaction of biological
      tissue with the metals. The best thickness of the tissues is 4 MUm.

PMID- 29367024
TI  - Synthesis, spectroscopic characterization (FT-IR, FT-Raman, and NMR), quantum
      chemical studies and molecular docking of 3-(1-(phenylamino)ethylidene)-chroman
      2,4-dione.
AB  - The experimental and theoretical investigations of structure of the 3-(1
      (phenylamino)ethylidene)-chroman-2,4-dione were performed. X-ray structure
      analysis and spectroscopic methods (FTIR and FT-Raman, 1H and 13C NMR), along
      with the density functional theory calculations (B3LYP functional with empirical
      dispersion corrections D3BJ in combination with the 6-311 + G(d,p) basis set),
      were used in order to characterize the molecular structure and spectroscopic
      behavior of the investigated coumarin derivative. Molecular docking analysis was
      carried out to identify the potency of inhibition of the title molecule against
      human's Ubiquinol-Cytochrome C Reductase Binding Protein (UQCRB) and
      Methylenetetrahydrofolate reductase (MTHFR). The inhibition activity was obtained
      for ten conformations of ligand inside the proteins.

PMID- 29367025
TI  - 2-Ethynylpyridine dimers: IR spectroscopic and computational study.
AB  - 2-ethynylpyridine (2-EP) presents a multifunctional system capable of
      participation in hydrogen-bonded complexes utilizing hydrogen bond donating (CH,
      Aryl-H) and hydrogen bond accepting functions (N-atom, CC and pyridine pi
      systems). In this work, IR spectroscopy and theoretical calculations are used to
      study possible 2-EP dimer structures as well as their distribution in an inert
      solvent such as tetrachloroethene. Experimentally, the CH stretching vibration of
      the 2-EP monomer absorbs close to 3300 cm-1, whereas a broad band with maximum
      around 3215 cm-1 emerges as the concentration rises, indicating the formation of
      hydrogen-bonded complexes involving the CH moiety. The CC stretching vibration of
      monomer 2-EP close to 2120 cm-1 is, using derivative spectroscopy, resolved from
      the signals of the dimer complexes with maximum around 2112 cm-1. Quantum
      chemical calculations using the B3LYP + D3 model with counterpoise correction
      predict that the two most stable dimers are of the pi-stacked variety, closely
      followed by dimers with intermolecular CH?N hydrogen bonding; the predicted red
      shifts of the CH stretching wavenumbers due to hydrogen bonding are in the range
      54-120 cm-1. No species with obvious hydrogen bonding involving the CC or
      pyridine pi-systems as acceptors are predicted. Dimerization constant at 25 
      degrees C is estimated to be K2 = 0.13 +/- 0.01 mol-1 dm3.

PMID- 29367026
TI  - A highly selective and sensitive Tb3+-acetylacetone photo probe for the
      assessment of acetazolamide in pharmaceutical and serum samples.
AB  - A novel, simple, sensitive and selective spectrofluorimetric method was developed
      for the determination of Acetazolamide in pharmaceutical tablets and serum
      samples using photo probe Tb3+-ACAC. The Acetazolamide can remarkably quench the
      luminescence intensity of Tb3+-ACAC complex in DMSO at pH 6.8 and lambdaex = 350
      nm. The quenching of luminescence intensity of Tb3+-ACAC complex especially the
      electrical band at lambdaem = 545 nm is used for the assessment of Acetazolamide
      in the pharmaceutical tablet and serum samples. The dynamic range found for the
      determination of Acetazolamide concentration is 4.49 * 10-9-1.28 * 10-7 mol L-1,
      and the limit of detection (LOD) and limit of quantification (LOQ) are (4.0 * 10
      9 and 1.21 * 10-8) mol L-1, respectively.

PMID- 29367027
TI  - Imidazole and beta-carotene photoprotection against photodynamic therapy
      evaluated by synchrotron infrared microscopy.
AB  - In order to better understand the role of beta-carotene and imidazole on the
      Photodynamic Therapy (PDT) mechanism, synchrotron infrared microscopy was used to
      detect the associated intracellular biochemical modifications following the
      visible light irradiation of HeLa cells incubated with these compounds as typical
      hydrophobic and hydrophilic singlet oxygen quenchers, respectively. For this
      purpose, PDT was performed employing the hydrophilic sensitizer 5,10,15,20
      Tetrakis (1-methyl-4-pyridinio) porphyrin tetra (p-toluenesulfonate), TMPyP, and
      the hydrophobic sensitizer 5-(4-Methoxycarboxyphenyl)-10,15,20-triphenyl-21H,23H
      porphyrin. The single cell IR spectra of PDT-treated, PDT plus quencher-treated
      and control HeLa cells were recorded at the SOLEIL Synchrotron Infrared SMIS
      beamline targeting specifically the cell nucleus. Principal Component Analysis
      (PCA) was used to assess the IR spectral changes. PCA revealed that there is a
      frequency shift of the protein Amide I vibrational band for the assays with the
      TMPyP sensitizer, indicating changes in the protein secondary structures of the
      PDT-treated cancer cells compared to the controls. In addition, the scores in
      those cells treated with both quenchers appear to be similar to the controls
      indicating a photoprotective effect. Comparative experiments carried out with
      SKMEL-28 and HaCat cells showed non- significant photoprotective effects of beta
      carotene and imidazole.

PMID- 29367028
TI  - New approach for determination of the influence of long-range order and selected
      ring oscillations on IR spectra in zeolites.
AB  - Vibrational spectroscopy can be considered as one of the most important methods
      used for structural characterization of various porous aluminosilicate materials,
      including zeolites. On the other hand, vibrational spectra of zeolites are still
      difficult to interpret, particularly in the pseudolattice region, where bands
      related to ring oscillations can be observed. Using combination of theoretical
      and computational approach, a detailed analysis of these regions of spectra is
      possible; such analysis should be, however, carried out employing models with
      different level of complexity and simultaneously the same theory level. In this
      work, an attempt was made to identify ring oscillations in vibrational spectra of
      selected zeolite structures. A series of ab initio calculations focused on S4R,
      S6R, and as a novelty, 5-1 isolated clusters, as well as periodic siliceous
      frameworks built from those building units (ferrierite (FER), mordenite (MOR) and
      heulandite (HEU) type) have been carried out. Due to the hierarchical structure
      of zeolite frameworks it can be expected that the total envelope of the zeolite
      spectra should be with good accuracy a sum of the spectra of structural elements
      that build each zeolite framework. Based on the results of HF calculations,
      normal vibrations have been visualized and detailed analysis of pseudolattice
      range of resulting theoretical spectra have been carried out. Obtained results
      have been applied for interpretation of experimental spectra of selected
      zeolites.

PMID- 29367029
TI  - Comparison of three surgical fixation methods for dual-bone forearm fractures in
      older children: A retrospective cohort study.
AB  - BACKGROUND: The aim of this study was to compare the outcomes of dual ESIN (D
      ESIN) fixation, hybrid fixation, and open reduction and dual plate (d-plate)
      fixation in the treatment of dual-bone forearm fractures in children aged 10-16
      years. MATERIALS AND METHODS: 137 patients with dual-bone forearm fractures (48
      patients in the D-ESIN group, 45 patients in the hybrid group, and 44 patients in
      the d-plate group) were reviewed. Duration of surgery, length of incision,
      intraoperative blood loss, intraoperative times of fluoroscopy, and duration of
      postoperative immobilisation were recorded. Radiographic outcomes, functional
      outcomes, and complication rate were also recorded. RESULTS: Surgeries and
      incisions were significantly shorter, and less intraoperative blood loss
      occurred, in the hybrid group than the d-plate group (P < 0.001). The hybrid
      group was also characterised by less intraoperative fluoroscopy times and shorter
      duration of postoperative immobilisation compared with the D-ESIN group (P <
      0.001). The union rate of the ulna at 3 months postoperatively was higher in the
      hybrid and d-plate groups than in the D-ESIN group (P = 0.003). The union rate of
      the radius was similar in all three groups (P = 0.403). No significant difference
      in the union rate of the radius or ulna was observed among groups at 6 months
      postoperatively (P = 0.052). The mean union time was notably later in the D-ESIN
      group than in the hybrid and d-plate groups. However, no significant difference
      in functional outcome or complication rate was observed among the three groups (P
      = 0.822 and P = 0.912). CONCLUSION: Hybrid fixation was superior in terms of the
      duration of surgery, intraoperative use of fluoroscopy, intraoperative blood
      loss, duration of postoperative immobilisation, delayed union of the ulna, and
      bone union time. Therefore, hybrid fixation is a safe and effective treatment for
      dual-bone forearm fractures in children aged 10-16 years.

PMID- 29367030
TI  - Reevaluation of the efficacy of preoperative computed tomography-guided hook wire
      localization: A retrospective analysis.
AB  - BACKGROUND: Small pulmonary nodules (SPNs) often cannot be accurately located
      during video-assisted thoracoscopic (VATS) resection, and preoperative computed
      tomography (CT)-guided localization performed using hook wire placement can be
      helpful. However, recent studies revealed a trend towards more frequent and
      severe complications occurring in association with hook wire insertion. The aim
      of this study is to reevaluate the safety, and reliability of the preoperative CT
      guided hook wire localization technique and also identify the risk factors for
      localization-related pneumothorax. METHODS: This retrospective study enrolled 95
      patients (with 105 pulmonary nodules) who underwent preoperative CT-guided hook
      wire localization and followed VATS resection from January 2013 to September
      2016. Univariate and multivariate logistic regression analyses were used to
      identify factors associated with localization-related pneumothorax. RESULTS: All
      the 105 nodules were successfully localized. Two (1.9%) hook wires dislodged
      before VATS resection. Mean largest diameter of the nodules was 10.1 mm (range, 3
      19 mm). Mean depth from the nearest pleural surface was 11.2 mm (range, 2-38 mm).
      Mean needle insertion depth was 24.3 mm (range, 4-49 mm), and mean procedure time
      was 17.3 min (range, 7-48 min). Asymptomatic pneumothorax was observed in 18
      patients (18.9%) and hemorrhage in 7 patients (7.4%). Multivariate logistic
      regression analysis revealed the number of needle insertions (OR 8.893, p =
      0.019) as the only significant independent risk factor of pneumothorax.
      CONCLUSIONS: CT-guided hook wire localization is a safe, reliable and convenient
      technique and can be applied widely to facilitate the resection of SPNs.
      Simultaneous localization for multiple nodules in ipsilateral lung may be
      associated with a higher risk of localization-related pneumothorax.

PMID- 29367031
TI  - Laparoscopic ventral hernia repair: Results of a two thousand patients
      prospective multicentric database.
AB  - Laparoscopic incisional and ventral hernia repair (LIVHR) has been largely
      employed by the surgical community worldwide, despite the use of different types
      of mesh and fixation devices. A large nationwide prospective multicentric
      database collected 2005 operations from 8 high-volume centers, to investigate the
      perioeperative and long-term outcomes. The laparoscopic operations were completed
      in 1979 patients (98.7%), with a mean age of 60.7 years and a Body Mass Index of
      28.8 kg/m2. Two hundred and one patient (18.8%) had a previous failed open
      repair. The average surface areas of the major defects were 47.4 and 18.2 cm 2
      for postincisional and primary hernias. The mean operation time and postoperative
      stay were 94.4 min and s 3.7 days, respectively. We collected a total of 50
      (2.5%) intraoperative and 414 (20.6%) postoperative complications, with
      reoperation needed in 38 cases (1.8%). After a mean follow-up period of 24
      months, we recorded 62 (3.8%) confirmed recurrences. Length of surgery, hospital
      stay, and a previous recurrence were all risk factors for recurrence. Primary
      hernias had better perioperative outcomes compared to incisional hernias, except
      for the pain. The laparoscopic approach of both post-incisional and primary
      hernias seemed to be safe and feasible in short-to medium-term periods.

PMID- 29367032
TI  - The seroprevalence rate and population genetic structure of human cystic
      echinococcosis in the Middle East: A systematic review and meta-analysis.
AB  - Cystic echinococcosis (CE) represents an increasing public health concern in many
      parts of the world, including the Middle East. The present study is the first
      systematic review and meta-analysis to assess the seroprevalence rate and
      population genetic structure of human CE in the eastern Mediterranean region. To
      estimate the population genetic structure, Echinococcus sequences of the
      cytochrome oxidase subunit 1 (cox1) gene isolated from countries from this
      geographical area were retrieved from the GenBank database. An electronic search
      for articles from 1990 until 2015 was performed using databases PubMed,
      ScienceDirect, and Scopus. A total of 53 articles reporting on CE seroprevalence
      and genotyping data met our eligibility criteria and were included in a meta
      analysis. The overall CE seroprevalence rates in the general population and in
      individuals at high risk of infection were estimated using the random-effect
      model at 7.4% (95% CI = 4.8-10.6) and 10.7% (95% CI = 7.6-14.3), respectively.
      Risk factors including age group (P < 0.001), dog ownership (P = 0.03), residence
      area (P < 0.001), and educational level (P = 0.04) showed a statistically
      significant association with CE seroprevalence. A pairwise fixation index (Fst),
      used as an estimation of gene flow, suggested a moderate level of genetic
      differentiation between members of the E. granulosus sensu stricto (G1-G3)
      complex from Iranian and Turkish metapopulations (Fst = 0.171). The finding of
      common haplotypes may represent an ancestral transfer of alleles among
      populations probably during the early stages of animal domestication. The high CE
      seroprevalence rates found highlight the necessity of implementing appropriate
      public education for preventive and control strategies, particularly in
      individuals at high risk of infection; furthermore, our genetic findings reveal
      novel molecular data concerning microevolutionary events of Echinococcus isolates
      among Middle East countries.

PMID- 29367033
TI  - Comparison of a single approach versus double approaches for the treatment of
      terrible traid of elbow-A retrospective study.
AB  - INTRODUCTION: Dislocation of the elbow associated with radial head and coronoid
      fracture, the so-called "terrible triad" of the elbow, is challenging to treat
      and has a history of complicated outcomes. This study is to compare the clinical
      outcome of a single lateral approach-the extensile splitting extensor digitorum
      communis (EDC) approach and combined lateral and medial (CML) approaches for the
      treatment of terrible traid of the elbow (TTE). MATERIAL AND METHODS: After
      appropriate exclusion, 60 TTE patients (28 patients in the EDC group, 32 patients
      in the CML group) from 2009 January to 2015 August were reviewed in this study.
      All included patients underwent open reduction, lateral collateral ligament
      complex repair, and postoperative function exercise. Surgical time,
      intraoperative blood loss, postoperative pain, elbow motion, MEPS score and
      complication rate were recorded and compared. RESULT: There were significant
      differences in surgery time (P < 0.05) and ulnar nerve lesion symptom, no patient
      suffered ulnar nerve lesion symptom in EDC group, but 5 patients in CML group
      suffered it. No differences were found in intraoperative blood loss,
      postoperative pain and heterotopic ossification (P > 0.05). Mean follow-up was
      26.1 months (from 24 to 30 months), at the final follow-up, 2 patients in EDC
      group and 4 patients in CML group required elbow release operation, mean flexion
      and extension (124.1 +/- 14.6 degrees and 8.3 +/- 5.3 degrees ), pronation and
      supination (73.4 +/- 5.3 degrees  and 74.4 +/- 6.0 degrees ) in EDC group were
      higher than CML group (114.2 +/- 15.0 degrees  and 17.6 +/- 8.0 degrees , 69.2 +/
      6.9 degrees  and 70.4 +/- 7.5 degrees , P < 0.05). Besides, MEPS score in the
      former group was also higher than the latter group (91.8 +/- 4.5 to 84.4 +/- 5.2,
      P < 0.01). CONCLUSION: The single lateral approach achieved better function
      recovery than combined lateral and medial approach, decreasing the risk of ulnar
      nerve lesion and surgery time for the treatment of TTE.

PMID- 29367034
TI  - Systematic review of anaesthetic medication for ERCP based on a network meta
      analysis.
AB  - AIMS: We performed a systematic review of various anaesthetic medications for
      endoscopic retrograde cholangiopancreatography (ERCP) and aimed to make a
      comprehensive comparison based on a network meta-analysis. METHODS: We searched
      globally recognized electronic databases, including PubMed, Cochrane Central and
      EMBASE, to retrieve relevant randomized controlled trials (RCTs) of anaesthetic
      medications for ERCP. Network meta-analysis was conducted by evaluating the
      procedure time, adverse effects and drug requirements. The cumulative probability
      P value was utilized to rank the medications under examination. RESULTS:
      Seventeen RCTs that examined 1877 patients were included in this research. Under
      good convergence and efficiency, data analysis was performed using a consistency
      model. For the comparison of procedure times, we found that a combination of
      dexmedetomidine and ketamine (P = 0.19) or propofol plus pethidine (P = 0.18)
      seemed to be the two best medications for reducing procedure time. Additionally,
      midazolam combined with dexmedetomidine plus pethidine seemed to be the safest
      application for ERCP (P = 0.36). Propofol plus alfentanil also exhibited a good
      safety value (P = 0.28). For evaluation of drug requirements, the whole network
      connection could not be established; thus, comparisons in two subgroups were
      conducted. The results showed that midazolam combined with dexmedetomidine plus
      pethidine (P = 0.41) and propofol plus refentanil (P = 0.94) were superior to
      others in decreasing drug requirements. CONCLUSIONS: Based on the objective
      results and our conclusions, we deemed that a combination of midazolam and
      dexmedetomidine was recommended, and propofol plus opioids also revealed great
      clinical value. However, we are still expecting more clinical research in the
      future.

PMID- 29367035
TI  - Multicolour versus monocolour inking specimens after pancreaticoduodenectomy for
      periampullary cancer: A single centre prospective randomised clinical trial.
AB  - BACKGROUND: R status represents an important prognostic factors in periampullary
      cancers. Thus, it is useful to verify if it can be influenced by different
      techniques of margination. METHODS: Single-centre, randomised clinical trial of
      patients affected by periampullary cancer who underwent pancreaticoduodenectomies
      which included two different types of margination: arm A (multicolour inking) and
      arm B (monocolour inking). The primary endpoint was the overall R1 resection rate
      and its difference between the two arms. The secondary endpoints were the R1
      resection rate in each margin and its difference between the two arms, and the
      impact of margin status on survival. RESULTS: Fifty patients were randomised, 41
      analysed: 22 in arm A, 19 arm B. The overall R1 status was 61%, without
      significant differences between the two arms. The margin most commonly involved
      was the superior mesenteric artery (SMA) (36.6%). A trend in favour of arm B was
      shown for the superior mesenteric artery margin (arm A = 22.7% versus arm B =
      52.6%; P = 0.060). The anterior surface (P = 0.015), SMA (P = 0.047) and
      pancreatic remnant (P = 0.018) margins significantly influenced disease-free
      survival. CONCLUSIONS: The R status was not influenced by different techniques of
      margination using a standardised pathological protocol. The SMA margin seemed to
      be the most important margin for evaluating both R status and disease-free
      survival.

PMID- 29367036
TI  - Outcomes after laparoscopic anti-reflux surgery related to obesity: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Laparoscopic Anti-Reflux Surgery (LARS) is an established alternative
      treatment to pharmacological therapy for patients with Gastro Osophageal Reflux
      Disease (GORD), yet its safety and efficacy in obese patients is controversial. A
      systematic review and meta-analysis was performed to compare LARS related to
      obesity. METHODS: Embase, MEDLINE and the Cochrane Library (January 1970 to July
      2017) were searched for studies reporting clinical outcomes of LARS in patient
      cohorts stratified by Body Mass Index (BMI). Data was grouped according to BMI,
      <30 kg/m2 (non-obese) and >=30 kg/m2 (obese). Primary outcome measures were
      reflux recurrence, operative morbidity, re-intervention (redo surgery and
      endoscopic dilatation), conversion to open surgery, and early return to theatre.
      Results were pooled in meta-analyses as Odds Ratios (OR). RESULTS: Thirteen
      eligible observational studies comparing LARS in non-obese (n = 6246) and obese
      (n = 1753) patients were identified. Recurrence of reflux was significantly lower
      in the non-obese cohort (OR 0.28, 95% C.I. 0.13 to 0.61, p = 0.001), however no
      significant differences were observed in rates of operative morbidity (OR 0.82,
      0.54 to 1.23, p = 0.33), redo surgery (OR 0.94, 0.51 to 1.72, p = 0.84),
      endoscopic dilatation (OR 0.98, 0.45 to 2.17, p = 0.97), conversion to open
      surgery (OR 0.96, 0.50 to 1.85, P = 0.90), or early return to theatre (OR 0.77,
      0.43 to 1.38, p = 0.39). CONCLUSIONS: LARS can be performed safely in obese
      patients, but risks higher GORD recurrence. Clinicians and patients should be
      aware that obesity may adversely affect LARS outcome and careful consideration be
      given in the consent process inherent within the optimal management of GORD.

PMID- 29367037
TI  - Central pancreatectomy with external drainage of monolayer pancreaticojejunostomy
      for prevention of postoperative pancreatic fistula: A retrospective cohort study.
AB  - OBJECTIVE: Postoperative pancreatic fistula (POPF) remains a common problem and
      leading cause of morbidity and mortality after central pancreatectomy (CP). The
      aim of this study was to present a technique of external drainage of monolayer
      pancreaticojejunostomy for prevention of POPF. METHODS: Patients received
      elective CP with external drainage of monolayer pancreaticojejunostomy between
      January 2010 and December 2016 were retrospectively analyzed. The occurrence and
      severity of POPF, overall complications, reoperation rate, in-hospital mortality,
      and length of postoperative hospital stay were measured. The 2016 updated
      definition and classification system of the International Study Group of
      Pancreatic Surgery (ISGPS) was used for POPF. In addition, a matched-pairs
      comparison with internal drainage of pancreaticojejunostomy was made. RESULTS: 33
      consecutive patients underwent CP with external drainage of monolayer
      pancreaticojejunostomy during this period. 4 (12.1%) cases developed grade B
      POPF, among which one patient was classified as having Clavien-Dindo
      classification IIIa complication. None of the patients developed grade C POPF,
      delayed gastric emptying, or postpancreatectomy hemorrhage. There was no
      reoperation or in-hospital mortality occurred. Matched-pairs comparison revealed
      that patients with external drainage of pancreaticojejunostomy had significantly
      lower incidence of POPF. CONCLUSION: External drainage of monolayer
      pancreaticojejunostomy seems effective in prevention of POPF after CP.

PMID- 29367038
TI  - Laparoscopic hepatectomy produces better outcomes for hepatolithiasis than open
      hepatectomy: An updated systematic review and meta-analysis.
AB  - BACKGROUND: The present meta-analysis focused on comparing the efficacy and
      safety of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) for
      hepatolithiasis. In detail, short-term outcomes including operative time,
      intraoperative blood loss, intraoperative blood transfusion, postoperative time
      to oral intake, length of hospital stay, overall postoperative complication rate,
      initial residual stone, and stone recurrence were analyzed systematically.
      METHODS: PubMed, Embase, Web of Science and Cochrane Library were comprehensively
      searched for eligible studies up to Jun. 30. 2017. Bibliographic citation
      management software (EndNoteX7) was applied to literature management. Quality
      assessment was carried out according to the modification of the Newcastle-Ottawa
      Scale (NOS). The data were analyzed by Stata SE12.0 (StataCorp, College Station,
      TX). Sensitivity analysis was conducted by deleting single study step by step.
      Odds ratio (OR) were calculated for dichotomous data, and standard mean
      difference (SMD) with 95% confidence intervals (CI) was calculated continuous
      data. RESULTS: A total of 17 eligible studies with 1351 patients were identified
      after a thorough literature search. The pooled results of the present meta
      analysis showed that laparoscopic approach was related to significantly less
      intraoperative estimated blood loss in patients with hepatolithiasis (SMD: -0.52;
      95% CI: -0.93 to -0.1; I2 = 91%; P < 0.0001); lower overall postoperative
      complication rate (OR: 0.52; 95% CI: 0.39 to 0.70; I2 = 0%; P < 0.0001) and
      intraoperative transfusion rate (OR = 0.25; 95% CI: 0.12 to 0.53; P < 0.0001; I2
      = 30.1%; P = 0.239); shorter time to oral intake (SMD: -1.66; 95% CI: -2.41 to 
      0.92; I2 = 91%; P < 0.0001), and shorter stay in hospital (SMD: -0.89; 95% CI: 
      1.19 to -0.59; I2 = 83%; P < 0.00001). However, no significant differences was
      detected between LH and OH in terms of operative time (SMD: 0.22; 95% CI: -0.21
      to 0.65; I2 = 92%; P = 0.31), initial residual stones (OR: 0.79; 95% CI: 0.50 to
      1.25; I2 = 0%; P = 0.31), and stone recurrence (OR: 0.67; 95% CI: 0.35 to 1.27;
      I2 = 0%; P = 0.22). In addition, our stratified analysis according to types of LH
      indicated that the laparoscopic approach still produced more favorable outcomes
      whatever patients underwent left lateral sectionectomy (LLS) or left
      hemihepatectomy (LHH). CONCLUSION: The laparoscopic hepatectomy is a better
      alternative to open approach in patients with hepatolithiasis, providing less
      overall complication rate, shorter postoperative stay of hospital stay, less
      blood loss, and shorter time to oral intake. However, high-quality randomized
      controlled trials (RCTs) are badly needed to provide higher-level evidence due to
      unavoidable bias from non-randomized trials.

PMID- 29367039
TI  - Immunohistochemistry testing for mismatch repair deficiency in Stage 2 colon
      cancer: A cohort study of two cancer centres.
AB  - BACKGROUND/OBJECTIVES: Adjuvant chemotherapy for Stage II colon cancer offers a
      small (2-3%) overall survival benefit and is not universally recommended.
      Mismatch repair deficiency (dMMR) confers an improved prognosis identifying
      patients unlikely to benefit from adjuvant chemotherapy. The aim of this study
      was to investigate the use of dMMR immunohistochemistry in two major cancer
      treatment centres. METHODS: Prospective data were collected on all patients with
      resected Stage II colon cancer between 2010 and 2015 across two large Australian
      hospitals. Data collected included patient demographics, tumour histology, dMMR
      immunohistochemistry, chemotherapy use, and outcomes. RESULTS: All 355 patients
      (56.1% female, median age 81) with resected Stage 2 Colon cancer entered on to
      the surgical database were included in this analysis. MMR testing was performed
      on 167 patient samples (47%), most occurred post-2013 (73.1% vs. 26.9% patients).
      dMMR rates were 34.1%. 25 (7.3%) received adjuvant chemotherapy, with no patient
      >80 years receiving treatment. Presence of >=2 high-risk feature increased the
      likelihood of adjuvant chemotherapy. Only 3.6% dMMR patients received
      chemotherapy; both were young with high-risk features. 27/288 (7.6%) patients
      (with follow up) relapsed, with 7 disease-free post-resection of metastatic
      disease, 9 are alive with metastatic disease, and 11 deceased. CONCLUSIONS:
      Unlike clinical trial populations, Stage 2 colon cancer patients are often
      elderly, have high rates of dMMR tumours, are rarely offered chemotherapy, yet
      still have excellent outcomes. dMMR immunohistochemistry is being increasingly
      used to identify Stage 2 patients who do not require chemotherapy.

PMID- 29367040
TI  - Short and long-term outcomes of laparoscopic total gastrectomy for gastric
      cancer: A single-center experience (retrospective cohort study).
AB  - BACKGROUND: Limited studies have been designed to evaluate the short and long
      term outcomes of laparoscopic total gastrectomy (LTG). The objective of this
      study was to evaluate the feasibility, safety, and oncological outcomes of LTG.
      METHODS: A total of 290 consecutive patients underwent radical gastrectomy for
      gastric cancer in our institution between 2010 and 2016, from which 110 were
      performed laparoscopically and included in the study. Short and long-term
      outcomes of LTG, such as operative results, postoperative courses, morbidities,
      and mortality, were investigated and compared with those of laparoscopy distal
      gastrectomy (LDG) patients. RESULTS: From the total of 110 patients who underwent
      LTG, no one underwent conversion. The mean operation time was 267 +/- 88 min. The
      mean reconstruction time was 45.3 +/- 15 min, and the mean intraoperative blood
      loss was 75.4 +/- 20 ml. The time until the first flatus was 4 +/- 1.5 days. The
      time to start soft diet was 7 +/- 1.8 days. The length of postoperative hospital
      stay was 9 +/- 2 days. The mean number of retrieved lymph nodes was 34.7 +/- 9.
      Compared with the LDG group, the mean operation time, the mean reconstruction
      time, number of retrieved lymph nodes, and time of start soft diet were
      significantly longer in the LTG group (P<0.05).The postoperative complication
      rates of the LTG group and LDG group were 10% and 8.3% (P>0.05), respectively.
      The 3-year cumulative survival rates of the LTG group and LDG group were 53.8%
      and 56.6% (P = 0.21), respectively. CONCLUSION: LTG for gastric cancer is a safe,
      reliable and minimally invasive procedure with short and long-term outcomes
      similar to those of LDG.

PMID- 29367041
TI  - Clinicopathological characteristics and prognostic factors of remnant gastric
      cancer: A single-center retrospective analysis of 90 patients.
AB  - BACKGROUND: The prognosis of remnant gastric cancer (RGC) is significantly poor.
      However, the mechanism and some clinical features of RGC have not been fully
      understood and are still under debate. MATERIALS AND METHODS: From January 2000
      to January 2014, 90 RGC patients were enrolled in this retrospective study.
      Patients were divided into two groups according to primary disease.
      Clinicopathological features and survival outcomes were compared between two
      groups. RESULTS: A total of 34 (37.8%) patients were diagnosed with remnant
      gastric cancer following benign disease (RGCB) and 56 (62.2%) were diagnosed with
      remnant gastric cancer following malignant disease (RGCM). The mean time interval
      from the primary operation to the development of RGC was 12.5 +/- 13.3 years in
      all RGC patients. The mean time interval in RGCB was significantly longer than
      that in RGCM (P < 0.01). The 1-, 2-, and 3- year overall survival rates of all
      patients were 56.1%, 38.2% and 33.2%, respectively. Univariate analysis indicated
      that tumor size, curability, histology type, serosa invasion, nodal involvement
      and distant metastasis were prognostic factors for RGC. The multivariate Cox
      regression analysis revealed that distant metastasis was an independent
      prognostic factor for RGC. CONCLUSION: RGC occurred earlier in patients with
      gastrectomy for primary malignant disease than for primary benign disease, even
      though the primary disease made no difference to the survival of RGC.
      Nonetheless, RGC patients experienced dismal overall survival. Therefore, early
      diagnosis plays a significant role in successfully carrying out curative
      resection and improving the prognosis for RGC.

PMID- 29367042
TI  - Sagittal orientation and uniform entry for thoracic pedicle screw placement with
      free-hand technique: A retrospective study on 382 pedicle screws.
AB  - BACKGROUND: One of the most important factors in obtaining a successful outcome
      in spinal surgery is appropriate placement of the pedicle screw. A number of
      different techniques are used to achieve successful pedicle screw placement. The
      free-hand technique has the advantage of no requirement for radiation exposure,
      but its success is highly dependent on surgeon experience. Here, we describe our
      entry point and perioperative sagittal orientation method, and evaluate
      postoperative sagittal alignment of pedicle screws with the free-hand pedicle
      screw placement technique. MATERIALS AND METHODS: Eighty-two patients undergoing
      spinal surgery between 2015 and 2016 were included in this study. Pedicle screw
      placement was evaluated retrospectively on postoperative anterior-posterior (A-P)
      and lateral load-bearing radiographs of the entire spinal column. The vertebral
      body was divided into five areas in the lateral plane. Sagittal orientation of
      the pedicle screws on lateral radiographs was evaluated by two spine surgeons
      with 3 years of experience and one radiologist experienced in musculoskeletal
      radiology, with each observer evaluating the image twice according to a 1-month
      interval. RESULTS: A total of 382 pedicle screws were evaluated. There was no
      statistically significant difference between the first and second measurements,
      performed by individual observers, and there was good concordance among the three
      observers. CONCLUSIONS: Use of a uniform entry point at all levels may increase
      the effectiveness of the free-hand technique and decrease the pedicle screw
      misplacement rate. Our technique may standardize the free-hand technique, which
      does not require radiation exposure, and make it more practical to apply
      uniformly.

PMID- 29367043
TI  - Conversion is a risk factor for postoperative anastomotic leak in rectal cancer
      patients - A retrospective cohort study.
AB  - AIM: The impact of conversion from laparoscopic surgery to laparotomy on the
      development of anastomotic leak (AL) in rectal cancer patients following
      laparoscopic low anterior resection (LAR) with total mesorectal excision (TME)
      has not been evaluated. The aim of this study was to evaluate the impact of
      conversion on the risk of AL and develop a prediction nomogram for postoperative
      AL. METHODS: All rectal cancer patients following laparoscopic LAR with TME from
      January 2010 to October 2014 were enrolled in the primary cohort. Comparisons of
      the postoperative anastomotic leak incidence rate between converted patients and
      non-converted patients were performed using both univariate and multivariate
      logistic regression analyses. The result of multivariable analysis was used to
      develop the predicting model and the performance of nomogram was assessed with
      respect to its calibration, discrimination, and clinical usefulness. An
      independent validation cohort containing 200 patients from November 2014 to
      October 2015 was assessed. RESULTS: Of all patients enrolled (n=646), 592 (91.6%)
      patients underwent totally laparoscopic surgery, and 54 (8.4%) were converted
      from laparoscopic surgery to laparotomy. Converted group patients were more
      likely to have a higher body mass index (BMI), prolonged length of stay (LOS),
      increased overall postoperative complication rates and advanced clinical T stage
      (T3 or T4), pathological N stage (N1 or N2) and pathological TNM stage (III or
      IV). The percentage of patients who had preoperative radiotherapy for rectal
      cancer was higher in non-converted patients. Patients who underwent conversion to
      laparotomy (n=10, 18.5%) were more likely to suffer from postoperative AL than
      those undergoing totally laparoscopic surgery (n=38, 6.4%) (P=0.004).
      Multivariate logistic regression analyses confirmed the association between
      conversion and postoperative AL (Odds ratio [OR], 95% confidence interval [CI]:
      2.71 [1.31-5.63], P=0.007). Conversion, gender, and clinical N stage incorporated
      in the individualized prediction nomogram showed good discrimination, with a C
      index of 0.697 (C-index, 0.621 and 0.772 through internal validation), and good
      calibration. In the validation cohort, the main results were consistent with the
      findings of the primary cohort, with a C-index of 0.670 (C-index, 0.562 and 0.777
      through internal validation). Decision curve analysis demonstrated that the
      prediction nomogram was clinically useful. CONCLUSION: Conversion during
      laparoscopic LAR was found to be associated with an increased risk for the
      postoperative AL in RC patients. A nomogram model incorporating conversion,
      gender and patient's clinical N stage seems to offers a useful tool for
      predicting postoperative AL in these patients.

PMID- 29367045
TI  - Suprapatellar versus infrapatellar approach for tibia intramedullary nailing: A
      meta-analysis.
AB  - OBJECTIVE: This meta-analysis was performed to determine the efficacy of
      suprapatellar versus infrapatellar approach for tibia intramedullary nailing
      (IMN). METHODS: A systematic search was performed in PubMed, Embase, Cochrane
      library, CNKI and Wanfang. Cochrane collaboration's tool and the Newcastle-Ottawa
      scale were used to evaluate literature qualities. Meta-analysis was performed
      using RevMan 5.3 software. RESULTS: Eight studies were eligible, including two
      randomized controlled trials (RCTs) and six retrospective cohort trials. There
      were no significant differences between suprapatellar and infrapatellar
      approaches in operation time, coronal plane alignment, and incidence of
      postoperative deep infection, nonunion and secondary operation. However,
      suprapatellar nailing achieved a significant shorter fluoroscopy time, less VAS
      pain score, better sagittal plane alignment and lower incidence of angular
      malalignment. Though pooled results indicated no significant difference in terms
      of final follow-up knee functional score, the RCT subgroup analysis showed that a
      higher knee functional score existed in suprapatellar group. CONCLUSIONS: For
      tibia IMN, suprapatellar approach might be superior to infrapatellar approach
      with shorter fluoroscopy time, less knee pain, better knee function recovery, and
      more accurate fracture reduction. Meanwhile, no increased risk of postoperative
      complications was identified. More RCTs are required for further research.

PMID- 29367044
TI  - Trauma patients with lower extremity and pelvic fractures: Should anti-factor Xa
      trough level guide prophylactic enoxaparin dose?
AB  - BACKGROUND: Adequate venous thromboembolism (VTE) prophylaxis is essential after
      trauma, especially in patients with lower extremity and/or pelvic fractures. We
      sought to investigate if prophylactic enoxaparin dosed by anti-Xa trough levels
      could reduce clinically evident VTE in trauma patients with lower extremity or
      pelvic injury. METHODS: Prospective data was collected on trauma patients
      admitted for at least two days with any lower extremity and/or pelvic fracture
      and who received enoxaparin for VTE prophylaxis between October 2013 and January
      2016. Patients in the control cohort received enoxaparin at 30 mg twice daily.
      Patients in the adjustment cohort had anti-Xa trough levels measured after three
      or more consecutive doses of enoxaparin. Those with a trough level of 0.1 IU/mL
      or lower had their dosage increased by 10-mg increments. RESULTS: Of the 159
      patients included, 58 (36.5%) were monitored with anti-Xa trough levels. The
      cohorts were similar in age, sex, regional AIS, ISS score, ICU and hospital
      length of stay, proportion of patients with diagnostic testing for VTE, and time
      to first enoxaparin dose. Initial enoxaparin dosing in the majority of patients
      (84.5%) who had anti-Xa trough levels measured was subprophylactic. Patients
      receiving enoxaparin dosed by anti-Xa trough level had a significantly lower VTE
      rate than those who did not (1.7% v. 13.9%, p = 0.03). CONCLUSIONS: Prophylactic
      enoxaparin adjusted by anti-factor Xa level may lead to a decreased rate of
      clinically evident VTE among trauma patients with lower extremity and/or pelvic
      fractures. Our findings indicate that the initial dose of enoxaparin was
      frequently too low.

PMID- 29367046
TI  - The effect of preoperative training on functional recovery in patients undergoing
      total knee arthroplasty: A systematic review and meta-analysis.
AB  - OBJECTIVE: A meta-analysis to evaluate the efficacy of preoperative training on
      functional recovery in patients undergoing total knee arthroplasty. METHOD:
      Randomized controlled trials (RCTs) about relevant studies were searched from
      PubMed (1996-2017.4), Embase (1980-2017.4), and the Cochrane Library (CENTRAL
      2017.4). Nine studies which evaluated the effect of preoperative training on
      functional recovery in patients undergoing TKA were included in our meta
      analysis. Meta-analysis results were collected and analyzed by Review Manager 5.3
      (Copenhagen: The Nordic Cochrane Center the Collaboration 2014). RESULTS: Nine
      studies containing 777 patients meet the inclusion criteria. Our pooled data
      analysis indicated that preoperative training was as effective as the control
      group in terms of visual analogue scale(VAS) score at ascend stairs (P = 0.41)
      and descend stars (P = 0.80), rang of motion (ROM) of flexion (P = 0.86) and
      extension (P = 0.60), short form 36 (SF-36) of physical function score (P = 0.07)
      and bodily pain score (P = 0.39), western Ontario and Macmaster universities
      osteoarthritis index (WOMAC) function score (P = 0.10), and time up and go (P =
      0.28). While differences were found in length of stay (P < 0.05). CONCLUSIONS:
      Our meta-analysis demonstrated that preoperative training have the similar
      efficacy on functional recovery in patients following total knee arthroplasty
      compared with control group. However, high quality studies with more patients
      were needed in future.

PMID- 29367047
TI  - Iron-based subsurface arsenic removal technologies by aeration: A review of the
      current state and future prospects.
AB  - Arsenic contamination in groundwater is a critical issue and one that raises
      great concern around the world as the cause of many negative health impacts on
      the human body, including internal and external cancers. There are many ways to
      remove or immobilize arsenic, including membrane technologies, adsorption, sand
      filtration, ion exchange, and capacitive deionization. These exhibit many
      different advantages and disadvantages. Among these methods, in-situ subsurface
      arsenic immobilization by aeration and the subsequent removal of arsenic from the
      aqueous phase has shown to be very a promising, convenient technology with high
      treatment efficiency. In contrast to most of other As remediation technologies,
      in-situ subsurface immobilization offers the advantage of negligible waste
      production and hence has the potential of being a sustainable treatment option.
      This paper reviews the application of subsurface arsenic removal (SAR)
      technologies as well as current modeling approaches. Unlike subsurface iron
      removal (SIR), which has proven to be technically feasible in a variety of
      hydrogeochemical settings for many years, SAR is not yet an established solution
      since it shows vulnerability to diverse geochemical conditions such as pH, Fe:As
      ratio, and the presence of co-ions. In some situations, this makes it difficult
      to comply with the stringent guideline value for drinking water recommended by
      the WHO (10 MUg L-1). In order to overcome its limitations, more theoretical and
      experimental studies are needed to show long-term application achievements and
      help the development of SAR processes into state-of-the-art technology.

PMID- 29367048
TI  - Comparison of Alcian blue and total carbohydrate assays for quantitation of
      transparent exopolymer particles (TEP) in biofouling studies.
AB  - Transparent exopolymer particles (TEP) and their precursors are gel-like acidic
      polysaccharide particles. Both TEP precursors and TEP have been identified as
      causal factors in fouling of desalination and water treatment systems. For
      comparison between studies, it is important to accurately measure the amount and
      fouling capacity of both components. However, the accuracy and recovery of the
      currently used Alcian blue based TEP measurement of different surrogates and
      different size fractions are not well understood. In this study, we compared
      Alcian blue based TEP measurements with a total carbohydrate assay method. Three
      surrogates; xanthan gum, pectin and alginic acid; were evaluated at different
      salinities. Total carbohydrate concentrations of particulates (>0.4 MUm) and
      their precursors (<0.4 MUm, >10 kDa) varied depending on water salinity and
      method of recovery. As xanthan gum is the most frequently used surrogate in
      fouling studies, TEP concentration is expressed as xanthan gum equivalents (mg
      XGeq/L) in this study. At a salinity of 35 mg/L sea salt, total carbohydrate
      assays showed a much higher particulate TEP fraction for alginic acid (38%)
      compared to xanthan gum (9%) and pectin (12%). The concentrations of particulate
      TEP therefore may only represent ~10% of the total mass; while precursor TEP
      represents ~80% of the total TEP. This highlights the importance of reporting
      both particulate and precursor TEP for membrane biofouling studies. The
      calculated concentrations of TEP and their precursors in seawater samples are
      also highly dependent on type of surrogate and resulting calibration factor. A
      linear correlation between TEP recovery and calibration factor was demonstrated
      in this study for all three surrogates. The relative importance and accuracy of
      measurement method, particulate size, surrogate type, and recovery are described
      in detail in this study.

PMID- 29367049
TI  - Degradation of organic pollutants by Vacuum-Ultraviolet (VUV): Kinetic model and
      efficiency.
AB  - Vacuum-Ultraviolet (VUV), an efficient and green method to produce hydroxyl
      radical (*OH), is effective in degrading numerous organic contaminants in aqueous
      solution. Here, we proposed an effective and simple kinetic model to describe the
      degradation of organic pollutants in VUV system, by taking the *OH scavenging
      effects of formed organic intermediates as co-existing organic matter in whole.
      Using benzoic acid (BA) as a *OH probe, *OH was regarded vital for pollutant
      degradation in VUV system, and the thus developed model successfully predicted
      its degradation kinetics under different conditions. Effects of typical
      influencing factors such as BA concentrations and UV intensity were investigated
      quantitatively by the model. Temperature was found to be an important influencing
      factor in the VUV system, and the quantum yield of *OH showed a positive linear
      dependence on temperature. Impacts of humic acid (HA), alkalinity, chloride, and
      water matrices (realistic waters) on the oxidation efficiency were also examined.
      BA degradation was significantly inhibited by HA due to its scavenging of *OH,
      but was influenced much less by the alkalinity and chloride; high oxidation
      efficiency was still obtained in the realistic water. The degradation kinetics of
      three other typical micropollutants including bisphenol A (BPA), nitrobenzene
      (NB) and dimethyl phthalate (DMP), and the mixture of co-existing BA, BPA and DMP
      were further studied, and the developed model predicted the experimental data
      well, especially in realistic water. It is expected that this study will provide
      an effective approach to predict the degradation of organic micropollutants by
      the promising VUV system, and broaden the application of VUV system in water
      treatment.

PMID- 29367050
TI  - The fate of antibiotic resistance genes and their potential hosts during bio
      electrochemical treatment of high-salinity pharmaceutical wastewater.
AB  - Pharmaceutical wastewaters containing antibiotics and high salinity can damage
      traditional biological treatment and result in the proliferation of antibiotic
      resistance genes (ARGs). Bioelectrochemical system (BES) is a promising approach
      for treating pharmaceutical wastewater. However, the fate of ARGs in BES and
      their correlations with microbial communities and horizontal genes transfer are
      unknown. In this study, we investigated the response of ARGs to bio
      electrochemical treatment of chloramphenicol wastewater and their potential hosts
      under different salinities. Three ARGs encoding efflux pump (cmlA, floR and
      tetC), one class 1 integron integrase encoding gene (intI1), and sul1 gene
      (associate with intI1) were analyzed. Correlation analysis between microbial
      community and ARGs revealed that the abundances of potential hosts of ARGs were
      strongly affected by salinity, which further determined the alteration in ARGs
      abundances under different salinities. There were no significant correlations
      between ARGs and intI1, indicating that horizontal gene transfer was not related
      to the important changes in ARGs. Moreover, the chloramphenicol removal
      efficiency was enhanced under a moderate salinity, attributed to the altered
      microbial community driven by salinity. Therefore, microbial community shift is
      the major factor for the changes of ARGs and chloramphenicol removal efficiency
      in BES under different salinities. This study provides new insights on the
      mechanisms underlying the alteration of ARGs in BES treating high-salinity
      pharmaceutical wastewater.

PMID- 29367051
TI  - Ecological patterns and adaptability of bacterial communities in alkaline copper
      mine drainage.
AB  - Environmental gradient have strong effects on community assembly processes. In
      order to reveal the effects of alkaline mine drainage (AlkMD) on bacterial and
      denitrifying bacterial community compositions and diversity in tailings
      reservoir, here we conducted an experiment to examine all and core bacterial taxa
      and denitrifying functional genes's (nirS, nirK, nosZIota) abundance along a
      chemical gradient in tailings water in Shibahe copper tailings in Zhongtiaoshan,
      China. Differences in bacterial and denitrifying bacterial community compositions
      in different habitats and their relationships with environmental parameters were
      analyzed. The results showed that the richness and diversity of bacterial
      community in downstream seeping water (SDSW) were the largest, while that in
      upstream tailings water (STW1) were the lowest. The diversity and abundance of
      bacterial communities tended to increase from STW1 to SDSW. The variation of
      bacterial community diversity was significantly related to electroconductibility
      (EC), nitrate (NO3-), nitrite (NO2-), total carbon (TC), inorganic carbon (IC)
      and sulfate (SO42-), but was not correlated with geographic distance in local
      scale. Core taxa from class to genus were all significantly related to NO3- and
      NO2-. Core taxa Rhodobacteraceae, Rhodobacter, Acinetobacter and Hydrogenophaga
      were typical denitrifying bacteria. The variation trends of these groups were
      consistent with the copy number of nirS, nirK and nosZIota, demonstrating their
      importance in the process of nitrogen reduction. The copy number of nirK,
      nosZIota and nirS/16S rDNA, nirK/16Sr DNA correlated strongly with NO3-, NO2- and
      IC, but nirS and nosZI/16SrDNA had no significant correlation with NO3- and NO2-.
      The copy numbers of denitrifying functional genes (nirS, nirK and nosZIota) were
      negatively correlated with heavy metal plumbum (Pb) and zinc (Zn). It showed that
      heavy metal contamination was an important factor affecting the structure of
      denitrifying bacterial community in AlkMD. In this study we have identified the
      distribution pattern of bacterial community along physiochemical gradients in
      alkaline tailings reservoir and displayed the driving force of shaping the
      structure of bacterial community. The influence of NO3-, NO2-, IC and heavy metal
      Pb and Zn on bacterial community might via their influence on the functional
      groups involving nitrogen, carbon and metal metabolisms.

PMID- 29367052
TI  - Construction and optimization of pH-sensitive nanoparticle delivery system
      containing PLGA and UCCs-2 for targeted treatment of Helicobacter pylori.
AB  - The acidic environment of the stomach is a threat to the curative effect of
      antimicrobial drugs for the eradication of Helicobacter pylori (H. pylori) in the
      infected area. The conventional clinical formulations of antibiotics have low
      specificity to H. pylori, which disrupts the normal balance of intestinal
      microbiomes. Therefore, oral drug delivery system with better stability at low pH
      as well as higher specificity to target H. pylori would provide more effective
      strategy to eradicate H. pylori and reduce the side effect of antibiotics. Based
      on the construction of UreI-mediated targeted drug delivery system developed by
      our group, in this work, using urea-modified UCCs-2 as targeting moiety to the
      UreI channel protein which is specifically expressed on H. pylori, pH-sensitive
      amoxicillin-loaded AMX-PLGA/UCCs-2 nanoparticles produced by UCCs-2 and PLGA for
      targeted treatment of H. pylori infection were established. The nanoparticles
      were prepared by double emulsion-solvent evaporation method. To achieve a
      promising drug delivery system with favorable pH-sensitive properties, we adopted
      an orthogonal design to obtain the optimal formulation. The results showed that
      the optimized AMX-PLGA/UCCs-2 nanoparticles were in a favorable pH sensitive
      manner and exhibited low cytotoxicity, higher specificity and better anti-H.
      pylori efficiency than amoxicillin and non-targeting AMX-PLGA/Cs nanoparticle
      both in vitro and in vivo, which can protect the antimicrobial drugs against
      acidic environment and deliver them to targeted eradicate H. pylori in the
      infected location. The cellular uptake mechanism showed that AMX-PLGA/UCCs-2
      nanoparticles are an effective UreI-mediated targeted drug delivery system for
      anti-H. pylori treatment, which can also be used as promising nanocarriers for
      oral delivery of other therapeutic drugs to targeted treat H. pylori.

PMID- 29367053
TI  - Mitigation of membrane biofouling by d-amino acids: Effect of bacterial cell-wall
      property and d-amino acid type.
AB  - Development of novel approaches for biofouling mitigation is of crucial
      importance for membrane-based technologies. d-amino acids (d-AAs) have been
      proposed as a potential strategy to mitigate biofouling. However, the effect of
      bacterial cell-wall properties and d-AAs type on biofouling mitigation remains
      unclear. This study assesses the effect of d-AAs type on membrane biofouling
      control, towards Gram positive (G+) and Gram negative (G-) bacteria. Three kinds
      of d-AAs were found to inhibit both G+ and G- bacterial attachment in short-term
      attachment and dead-end filtration experiments. The existence of d-AAs reduces
      extracellular polysaccharides and proteins on the membrane, which may decrease
      membrane biofouling. Cross-flow filtration tests further indicated that d-AAs
      could effectively reduce membrane biofouling. The permeate flux recovery post
      chemical cleaning, improved for both P. aeruginosa and B. subtilis treated with d
      AAs. The results obtained from this study enable better understanding of the role
      of d-AAs species on bacterial adhesion and biofilm formation. This may provide a
      new way to regulate biofilm formation by manipulating the species of d-AAs
      membrane systems.

PMID- 29367054
TI  - Bacterial proliferation on clay nanotube Pickering emulsions for oil spill
      bioremediation.
AB  - Halloysites (tubular aluminosilicate) are introduced as inexpensive natural
      nanoparticles that form and stabilize oil-water emulsions. Pickering
      emulsification can proceed with energies low enough to be afforded by ocean
      turbulence and the stability of droplets extends over more than a week. The
      oil/water interface is shown to be roughened and bacteria, which are added for
      oil degradation, are better attached to such oil droplets than to droplets
      without halloysites. The metabolic activity of Alcanivorax borkumensis,
      alkanotrophic bacteria widely distributed in marine environments, is enhanced by
      halloysite addition. A halloysite-based dispersant system is therefore
      environmentally friendly and promising for further optimization. The key elements
      of the described formulations are natural clay nanotubes, which are abundantly
      available in thousands of tons, thus making this technology scalable for
      environmental remediation.

PMID- 29367055
TI  - Characterization of the occult nature of frequently occurring pediatric motor
      vehicle crash injuries.
AB  - BACKGROUND: Occult injuries are those likely to be missed on initial assessment
      by first responders and, though initially asymptomatic, they may present suddenly
      and lead to rapid patient decompensation. No scoring systems to quantify the
      occultness of pediatric injuries have been established. Such a scoring system
      will be useful in the creation of an Advanced Automotive Crash Notification
      (AACN) system that assists first responders in making triage decisions following
      a motor vehicle crash (MVC). STUDY DESIGN: The most frequent MVC injuries were
      determined for 0-4, 5-9, 10-14 and 15-18 year olds. For each age-specific injury,
      experts with pediatric trauma expertise were asked to rate the likelihood that
      the injury may be missed by first responders. An occult score (ranging from 0-1)
      was calculated by averaging and normalizing the responses of the experts polled.
      RESULTS: Evaluation of all injuries across all age groups demonstrated greater
      occult scores for the younger age groups compared to older age groups (mean
      occult score 0-4yo: 0.61 +/- 0.23, 5-9yo: 0.53 +/- 0.25, 10-14yo: 0.48 +/- 0.23,
      and 15-18yo: 0.42 +/- 0.22, p < 0.01). Body-region specific occult scores
      revealed that experts judged abdominal, spine and thoracic injuries to be more
      occult than injuries to other body regions. CONCLUSIONS: The occult scores
      suggested that injuries are more difficult to detect in younger age groups,
      likely given their inability to express symptoms. An AACN algorithm that can
      predict the presence of clinically undetectable injuries at the scene can improve
      triage of children with these injuries to higher levels of care.

PMID- 29367057
TI  - Estrogen receptor alpha- (ERalpha), but not ERbeta-signaling, is crucially
      involved in mechanostimulation of bone fracture healing by whole-body vibration.
AB  - Mechanostimulation by low-magnitude high frequency vibration (LMHFV) has been
      shown to provoke anabolic effects on the intact skeleton in both mice and humans.
      However, experimental studies revealed that, during bone fracture healing, the
      effect of whole-body vibration is profoundly influenced by the estrogen status.
      LMHFV significantly improved fracture healing in ovariectomized (OVX) mice being
      estrogen deficient, whereas bone regeneration was significantly reduced in non
      OVX, estrogen-competent mice. Furthermore, estrogen receptors alpha (ERalpha) and
      beta (ERbeta) were differentially expressed in the fracture callus after whole
      body vibration, depending on the estrogen status. Based on these data, we
      hypothesized that ERs may mediate vibration-induced effects on fracture healing.
      To prove this hypothesis, we investigated the effects of LMHFV on bone healing in
      mice lacking ERalpha or ERbeta. To study the influence of the ER ligand estrogen,
      both non-OVX and OVX mice were used. All mice received a femur osteotomy
      stabilized by an external fixator. Half of the mice were sham-operated or
      subjected to OVX 4 weeks before osteotomy. Half of each group received LMHFV with
      0.3 g and 45 Hz for 20 min per day, 5 days per week. After 21 days, fracture
      healing was evaluated by biomechanical testing, MUCT analysis, histomorphometry
      and immunohistochemistry. Absence of ERalpha or ERbeta did not affect fracture
      healing in sham-treated mice. Wildtype (WT) and ERbeta-knockout mice similarly
      displayed impaired bone regeneration after OVX, whereas ERalpha-knockout mice did
      not. Confirming previous data, in WT mice, LMHFV negatively affected bone repair
      in non-OVX mice, whereas OVX-induced compromised healing was significantly
      improved by vibration. In contrast, vibrated ERalpha-knockout mice did not
      display significant differences in fracture healing compared to non-vibrated
      animals, both in non-OVX and OVX mice. Fracture healing in ERbeta-knockout mice
      was similarly affected by LMHFV as in WT mice. These results suggest that ERalpha
      signaling may be crucial for vibration-induced effects on fracture healing,
      whereas ERbeta-signaling may play a minor role.

PMID- 29367056
TI  - Histamine H4 receptor as a novel therapeutic target for the treatment of Leydig
      cell tumours in prepubertal boys.
AB  - Leydig-cell tumours (LCTs) are rare endocrine tumours of the testicular
      interstitium, with recent increased incidence. Symptoms include precocious
      puberty in children; and erectile dysfunction, infertility and/or gynaecomastia,
      in adults. So far, scientific evidence points to aromatase (CYP19) overexpression
      and excessive oestrogen and insulin-like growth factor (IGF) -1 production as
      responsible for Leydig-cell tumourigenesis. LCTs are usually benign; however,
      malignant LCTs respond poorly to chemo/radiotherapy, highlighting the need to
      identify novel targets for treatment. Herein, we investigated the potential role
      of the histamine receptor H4 (HRH4) as a therapeutic target for LCTs using R2C
      rat Leydig tumour cells, a well-documented in vitro model for Leydigioma. Also,
      we studied for the first time the expression of CYP19, IGF-1R, oestrogen receptor
      (ER) alpha, ERbeta, androgen receptor (AR) and HRH4 in human prepubertal LCTs
      versus normal prepubertal testes (NPTs). HRH4 agonist treatment inhibited
      steroidogenesis and proliferation in R2C cells and also negatively affected their
      pro-angiogenic capacity in vitro and in vivo, as assessed by evaluating the
      proliferative activity of human umbilical vein endothelial cells and by means of
      the quail chorioallantoic membrane assay, respectively. Moreover, E2 and IGF-1
      inhibited HRH4 mRNA and protein levels. In human prepubertal LCTs, CYP19, IGF-1R,
      ERalpha and ERbeta were overexpressed compared with NPTs. In contrast, HRH4
      staining was weak in LCTs, but moderate/strong and confined to the interstitium
      in NPTs. Importantly, HRH4 was absent or barely detectable in seminiferous
      tubules or germ cells. Overall, our results point to HRH4 as a novel therapeutic
      target in LCTs.

PMID- 29367058
TI  - Bipolar disorder and tobacco smoking: Categorical and dimensional clinical
      correlates in subjects from the Brazilian bipolar research network.
AB  - BACKGROUND: People with bipolar disorder (BD) have high rates of smoking.
      However, the scientific literature examining the association between clinical
      outcomes in BD and tobacco smoking is still limited and there are conflicting
      results. The objective of the current study was to comprehensively investigate
      associations between BD and tobacco smoking in a large Brazilian sample. METHODS:
      This study evaluated 336 outpatients from the Brazilian Bipolar Research Network,
      which is a collaboration between three large academic centers in Brazil. MAIN
      FINDINGS: Regarding the categorical analysis (i.e. current smokers versus non
      smokers), tobacco smokers showed: 1) a higher percentage of individuals
      identifying as Non-Caucasians; 2) a longer duration of illness; 3) a longer
      duration of untreated illness; 4) more severe manic symptoms; 4) a stronger
      family history of mood disorder; and 6) a higher current prevalence of
      alcohol/substance use disorder. The dimensional analysis in smokers (i.e. number
      of cigarettes per day versus clinical variables) found a positive correlation
      between number of cigarettes per day and a) age, b) age at onset of BD, c)
      duration of illness, and d) current diagnosis of panic disorder. CONCLUSION: This
      study found important clinical correlates of tobacco smoking in BD subjects. We
      observed that the variables associated with current smoker status (categorical
      approach) are not necessarily correlated with number of cigarettes per day
      (dimensional approach). Duration of illness appears to be a particularly relevant
      clinical variable in the association between BD and tobacco smoking.

PMID- 29367059
TI  - Precuneus-related regional and network functional deficits in social anxiety
      disorder: A resting-state functional MRI study.
AB  - BACKGROUND: Neuroimaging findings suggest that social anxiety disorder (SAD) may
      be correlated with changes in regional- or network-level brain function. However,
      few studies have explored alterations in intrinsic resting cerebral function in
      patients with SAD at both the regional and network levels, particularly focusing
      on the theory of mind (ToM)-related regions. This study was performed to
      investigate changes in neural activity and functional connectivity (FC) in ToM
      related regions during the resting state in SAD patients and to determine how
      these alterations are correlated with the clinical symptoms of SAD. METHODS:
      Forty-three SAD patients and 43 matched healthy controls underwent resting-state
      functional magnetic resonance imaging (rsfMRI) scans. First, the amplitude of low
      frequency fluctuation (ALFF) approach was used to explore regional activity.
      Then, the ToM-related region, i.e., the left precuneus, which showed altered ALFF
      values, was adopted as a seed for further FC analyses to assess network-level
      alterations in SAD. Between-group differences were compared using voxel-based two
      sample t-tests (P<0.05, with Gaussian random field correction). Pearson's
      correlation analyses were performed to examine relationships between alterations
      in ALFF and FC and clinical symptoms. RESULTS: Compared with the healthy
      controls, SAD patients showed decreased ALFF in the bilateral putamen (PUT) and
      left supplementary motor area (SMA) and increased ALFF in the right inferior
      parietal lobule (IPL), left precuneus and right cerebellar posterior lobe.
      Moreover, SAD patients exhibited lower connectivity between the left precuneus
      and the cerebellar posterior lobe, right inferior temporal gyrus (ITG), right
      parahippocampal gyrus (PHG) and left medial prefrontal cortex (mPFC). The altered
      ALFF values in the left precuneus and the hypoconnectivity between the left
      precuneus and left cerebellar posterior lobe were correlated with the patients'
      clinical symptoms (P<0.05). CONCLUSION: The precuneus, a ToM-related region, was
      altered at both the regional and network level in patients with SAD. Pathological
      fear and avoidance in SAD were correlated with abnormal regional function in the
      precuneus, whereas depression and anxiety were primarily correlated with
      functional deficits in the precuneus-related network. The altered FC within the
      precuneus-cerebellar region may reflect an imbalance in the neuromodulation of
      anxiety and depressive symptoms in SAD. These findings may facilitate a greater
      understanding of potential SAD neural substrates and could be used to identify
      potential targets for further treatment.

PMID- 29367060
TI  - Hippocampal shape alterations in healthy young women with familial risk for
      unipolar depression.
AB  - BACKGROUND: Although reduced hippocampal volume (HCV) is a common finding in
      depression, it is unclear whether the structural alterations leading to reduction
      of HCV are pre-existing risk factors before the onset of clinical symptoms or a
      cumulative process that begins with the onset of clinical symptoms. The aim of
      the present study was to understand the anatomical status of the hippocampus
      prior to the clinical symptoms in subjects with high familial risk for
      depression. METHODS: Twenty-seven young women (mean age: 22.3 +/- 2.1 years) who
      were at high risk for familial unipolar depression and 26 age- and gender-matched
      healthy controls (mean age: 22.1 +/- 2.1 years) with low familial risk for
      depression were included in the study. Total hippocampal volumes were measured by
      manual tracing. For 3D shape differences, the spherical harmonic basis functions
      (SPHARM) software was used. The segmented images were parameterized, and the
      point-to-point based group difference was compared by the Hotelling's T-squared
      test with total brain volume and Beck Depression Scale as covariates. RESULTS:
      Although there was no difference in overall HCVs, shape analyses revealed a
      contracted area on the Cornu Ammonis (CA) 1 region of the right hippocampus head
      in the high-risk group compared to the low-risk group. Cross-sectional design and
      small sample size, including only females, were the main limitations of this
      study. CONCLUSION: This study with shape analyses provided data suggesting that
      local structural hippocampal alterations in the CA1 region might be associated
      with depression vulnerability in women at high risk.

PMID- 29367061
TI  - Hierarchical heterostructures of p-type bismuth oxychloride nanosheets on n-type
      zinc ferrite electrospun nanofibers with enhanced visible-light photocatalytic
      activities and magnetic separation properties.
AB  - P-type bismuth oxychloride (p-BiOCl) nanosheets were uniformly grown on n-type
      zinc ferrite (n-ZnFe2O4) electrospun nanofibers via a solvothermal technique to
      form hierarchical heterostructures of p-BiOCl/n-ZnFe2O4 (p-BiOCl/n-ZnFe2O4 H-Hs).
      The density and loading amounts of the BiOCl nanosheets with exposed {0 0 1}
      facets were easily controlled by adjusting the reactant concentration in the
      solvothermal process. The p-BiOCl/n-ZnFe2O4 H-Hs exhibited enhanced visible-light
      photocatalytic activities for the degradation of Rhodamine B (RhB). The apparent
      first-order rate of the p-BiOCl/n-ZnFe2O4 H-Hs and its normalized constant were
      about 12.6- and 8-fold higher than pure ZnFe2O4 nanofibers. This suggests that
      both the improved charge separation efficiency from the uniform p-n
      heterojunctions and the enlarged active surface sites from the hierarchical
      structures increase the photocatalytic performances. Furthermore, the p-BiOCl/n
      ZnFe2O4 H-Hs could be efficiently separated from the solution with an external
      magnetic field via the ferromagnetic behavior of ZnFe2O4 nanofibers. The magnetic
      p-BiOCl/n-ZnFe2O4 H-Hs with enhanced visible-light photocatalytic performances
      might have potential applications in water treatment.

PMID- 29367062
TI  - A facile route for the syntheses of Ni(OH)2 and NiO nanostructures as potential
      candidates for non-enzymatic glucose sensor.
AB  - In modern world, diabetes is one of the most leading diseases that cause human
      death and disability. Continuous effort to control and manage diabetes by acute
      monitoring of the blood glucose concentration requires the development of an
      efficient and reliable glucose sensing device. Although both enzymatic and enzyme
      free methods of glucose detection are available in the market, non-enzymatic
      biosensors are more significant due to certain drawbacks in enzyme based sensors.
      In this article, a stable non-enzymatic sensing platform for d-glucose based on
      nickel hydroxide and nickel oxide nanomaterials has been described. Ni(OH)2 and
      NiO were synthesized through a facile hydrothermal route followed by the heat
      treatment. Detailed morphological and structural characterizations were carried
      out using GIXRD, transmission and scanning electron microscopy) (TEM and FESEM)
      which reveal that hexagonal beta-Ni(OH)2 and cubic NiO phases have been formed.
      TEM image of NiO has shown that the nanomaterials consist of ca. 10 nm sized rod
      like pattern distributed uniformly. Both Ni(OH)2 and NiO have shown excellent
      electrocatalytic activity towards enzyme-free glucose sensing under ambient
      condition. Glucose sensing investigation based on amperometric i-t curve
      performed in 0.2 M NaOH medium shows a good sensitivity of 12.09 uA mM-1 cm-2 and
      24.0 uA mM-1 cm-2, respectively for Ni(OH)2 and NiO nanostructures. Interference
      test was done using reagents like ascorbic acid, uric acid and dopamine to
      confirm the selectivity of nickel hydroxide and oxide nanomaterials towards
      glucose analyte. So, the proposed Ni(OH)2 and NiO based electrodes can be used as
      a cost-effective, stable and non-air sensitive platform for non-enzymatic glucose
      detection.

PMID- 29367063
TI  - Interaction of NaOH solutions with silica surfaces.
AB  - HYPOTHESIS: Sodium adsorption on silica surfaces depends on the solution counter
      ion. Here, we use NaOH solutions to investigate basic environments. SIMULATIONS:
      Sodium adsorption on hydroxylated silica surfaces from NaOH solutions were
      investigated through molecular dynamics with a dissociative force field, allowing
      for the development of secondary molecular species. FINDINGS: Across the NaOH
      concentrations (0.01 M - 1.0 M), ~50% of the Na+ ions were concentrated in the
      surface region, developing silica surface charges between - 0.01 C/m2 (0.01 M
      NaOH) and - 0.76 C/m2 (1.0 M NaOH) due to surface site deprotonation. Five inner
      sphere adsorption complexes were identified, including monodentate, bidentate,
      and tridentate configurations and two additional structures, with Na+ ions
      coordinated by bridging oxygen and hydroxyl groups or water molecules.
      Coordination of Na+ ions by bridging oxygen atoms indicates partial or complete
      incorporation of Na+ ions into the silica surface. Residence time analysis
      identified that Na+ ions coordinated by bridging oxygen atoms stayed adsorbed
      onto the surface four times longer than the mono/bi/tridentate species,
      indicating formation of relatively stable and persistent Na+ ion adsorption
      structures. Such inner-sphere complexes form only at NaOH concentrations of > 0.5
      M. Na+ adsorption and lifetimes have implications for the stability of silica
      surfaces.

PMID- 29367064
TI  - A facile strategy for the synthesis of ferroferric oxide/titanium
      dioxide/molybdenum disulfide heterostructures as a magnetically separable
      photocatalyst under visible-light.
AB  - Semiconductor photocatalysts is a promising approach to combat both environmental
      pollution and global energy shortage despite the challenges of recycling and
      stability. In this paper, magnetic Fe3O4 particle is introduced in the system and
      Fe3O4/TiO2/MoS2 heterostructures can be formed in a facile strategy. The
      morphology and structure of Fe3O4/TiO2/MoS2 can be controlled by adjusting the
      hydrolysis rate of the titanium source. MoS2 is designed to fill in the
      mesoporous of TiO2 core, forming heterojunction on the surface and near-surface
      of TiO2 under solvothermal conditions. With respect to the decomposition of a
      rhodamine B (RhB) solution under visible light, the Fe3O4/TiO2/MoS2
      heterostructures display highly photocatalytic activities in aqueous solutions,
      and they can be easily recovered to realize cyclic utilization by applying an
      external magnetic field. Thus, the effective magnetic recycle of the catalyst is
      achieved, and high visible light catalytic activity is ensured simultaneously.
      Since the current method is simple and flexible to create recyclable catalysts
      with high stability in this way, it could promote the practicability of
      semiconductor photocatalysts in water treatment, degradation of dye pollutants,
      and environmental cleaning.

PMID- 29367065
TI  - Mesoporous tungsten oxide modified by nanolayered manganese-calcium oxide as
      robust photoanode for solar water splitting.
AB  - Described herein is the synthesis, characterization and photoelectrochemical
      behavior of a novel composite consisting of nanolayered manganese-calcium oxide
      (MCO) and mesoporous tungsten trioxide (WO3). The samples were characterized by
      transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results
      demonstrated that superior interfacial contacts had been formed between WO3 and
      MCO. UV-vis diffuse reflectance spectroscopy (DRS), photoelectrochemical
      characterization, and incident photon-to-current efficiency (IPCE) revealed an
      enhanced light harvesting and effective electron-hole separation. A
      photoelectrochemical (PEC) cell composed of the n-type MCO/WO3 as a photoanode
      and platinum sheet as a counter electrode was assembled to estimate the
      feasibility for overall water splitting under a solar simulator illumination. The
      photocatalytic hydrogen and oxygen production from the photochemical cell with
      optimized photocatalyst (MCO/WO3-9) under 2 h simulated solar light irradiation
      was 1.9 MUmol and 0.7 MUmol, respectively, at low extra bias (0.90 V vs. RHE).
      Our investigation suggests that coupling MCO with n-type semiconductor WO3 as
      photoanode is a promising method to improve the activity of overall water
      splitting to generate oxygen and hydrogen.

PMID- 29367066
TI  - Effect of ionic strength and salt identity on poly(N-isopropylacrylamide) brush
      modified colloidal silica particles.
AB  - HYPOTHESIS: The thermoresponse of poly(N-isopropylacrylamide) stabilised
      particles is influenced by the presence of salt and is dependent on the
      concentration, and ions present. The conformation and electrophoretic mobility of
      core/shell PNIPAM brush modified silica particles is expected to vary as a
      function of these specific ion effects. EXPERIMENTS: The thermoresponse of PNIPAM
      brush modified silica particles was investigated via dynamic light scattering and
      electrophoretic mobility measurements between 5 and 45  degrees C in the presence
      of 11 different salt solutions. FINDINGS: Specific ion effects were observed in
      the presence of salt solutions for concentrations between 50 and 1000 mM. The
      temperature response could be mapped to a master curve unlike PNIPAM brush
      behaviour on planar substrates. The magnitude of brush layer lower critical
      solution temperature reduction was found to follow the order F- > CH3CO2- > Cl- >
      NO3- ~ Br- > I- > SCN- for the potassium series and Na+ > K+ > Cs+ > Li+ ~ NH4+
      for the chloride salts. The electrophoretic mobility of the modified particles in
      the presence of 100 mM potassium salts increased in magnitude as the brush layer
      collapsed and also with the chaotropic nature of the anion.

PMID- 29367067
TI  - Investigating the impact of sugar-based surfactants structure on surface tension
      at critical micelle concentration with structure-property relationships.
AB  - HYPOTHESIS: Surface tension of aqueous solutions of surfactants at their critical
      micelle concentrations (gammaCMC), may be quantitatively linked to the surfactant
      structure using Quantitative Structure Property Relationships (QSPR), all other
      factors held equal (temperature, presence of additive or salts). Thus, QSPR
      models can allow improved understanding and quantification of structure-gammaCMC
      trends, direct gammaCMC predictions, and finally help to design renewable
      substitutes for petroleum-based surfactants. EXPERIMENTS AND METHODS: A dataset
      of 70 gammaCMC of single surfactants at ambient temperature has been gathered
      from several research papers. Then, descriptors of the whole structure, of polar
      heads and of alkyl chains of the 70 surfactants were calculated and introduced in
      multilinear regressions to evidence the most predictive and physically meaningful
      structure property relationships. FINDINGS: The best model, based on quantum
      chemical descriptors, achieved a standard error of 2.4 mN/m on an external
      validation. Simpler models were also achieved based solely on the count of H
      atoms of the polar head but with prediction error of 2.9 mN/m. Among all
      identified factors affecting gammaCMC of sugar-based surfactants (polar head
      size, alkyl chain length and branching), polar head size was found to exhibit the
      only effect clearly taken into account by all the models.

PMID- 29367068
TI  - Characterization of EDTA-cross-linked beta-cyclodextrin grafted onto Fe-Al
      hydroxides as an efficient adsorbent for methylene blue.
AB  - The synthesis process of Fe-Al hydroxides coated with ethylenediaminetetraacetic
      acid (EDTA)-cross-linked beta-cyclodextrin polymer (FA-ECD) and its utilization
      in the adsorption of methylene blue (MB) were investigated. The FA-ECD before and
      after adsorption was characterized by scanning electron microscopy (SEM),
      Brunauer-Emmet-Teller (BET) analysis, Fourier-transform infrared (FTIR)
      spectroscopy, thermogravimetric (TG) analysis, and X-ray diffraction (XRD). In
      addition, the EDTA and beta-cyclodextrin contents were determined quantitatively.
      The optimization of several variables such as contact time, pH, initial
      concentration, and adsorbent dosage achieved the maximum removal percentages in
      mild conditions. The results revealed that the adsorption process mainly depended
      on the pH value and the optimal adsorption capacity of the MB was 60.71 mg/g at
      pH 8. Subsequently, the experimental equilibrium data at different temperatures
      were fitted with the Langmuir, Freundlich, and Dubinin-Radushkevich (D-R)
      isotherm models; the Freundlich model provided the best results. In addition, the
      pseudo-second-order kinetic model best described the adsorption of the MB. The
      thermodynamic analysis proved that the adsorption process was endothermic and
      spontaneous.

PMID- 29367069
TI  - Significance of Liquid Biopsy for Monitoring and Therapy Decision of Colorectal
      Cancer.
AB  - PURPOSE: Despite therapeutic improvements, all patients with nonresectable
      metastatic colorectal cancer (mCRC) acquire resistance to treatment probably due
      to the growth of mutated clones. In contrast to tissue-based studies, liquid
      biopsies have enabled the opportunity to reveal emerging resistance to treatment
      by detecting mutated clones and noninvasively monitoring clonal dynamics during
      therapy. METHODS: The courses of three patients with mCRC who were initially RAS
      wild-type were monitored longitudinally using liquid biopsy with long-term follow
      up of up to 20 sequential samples. Detection of fragmented RAS mutated
      circulating cell-free DNA (cf)DNA in plasma was performed by BEAMing. In
      addition, plasma digital droplet PCR was used to detect and quantify BRAF and
      PIK3CA mutated cfDNA. Changes of mutational load were correlated with imaging
      data. RESULTS: A combination of liquid biopsy and radiological imaging enabled
      visualization of the occurrence of clonal redistribution after discontinuation of
      anti-EGFR mAb therapy, as well as emerging RAS mutations during therapy with anti
      EGFR mAb indicating resistance. Furthermore, we found that growth of RAS mutated
      clones is independent of direct selective pressure by anti-EGFR therapy, which is
      a significant and new finding of this study. CONCLUSIONS: Our findings
      demonstrated the whole spectrum of clonal selection and redistribution of mutated
      cell clones leading to acquired resistance. Given our observation that the growth
      of RAS mutated clones can evolve even in the absence of anti-EGFR mAb therapy,
      there is a clear imperative to monitor RAS mutations in serial blood draws in all
      RAS wild-type patients in general and independent of the therapy.

PMID- 29367070
TI  - Circulating Exosomal miR-17-5p and miR-92a-3p Predict Pathologic Stage and Grade
      of Colorectal Cancer.
AB  - : Exosomes are extracellular membrane vesicles of 50- to 130-nm diameter secreted
      by most tumor cells. Exosomes can mediate the intercellular transfer of proteins
      and RNAs, including microRNAs (miRNAs), and promote both tumorigenesis and
      premetastatic niche formation. In this study, we performed exosomal RNA
      sequencing to identify candidate exosomal miRNAs that could be associated with
      colorectal cancer (CRC) and its distant metastasis. The expression profiles of
      exosomal miRNA, as secreted by isogenic human primary CRC cell line SW480 and
      highly metastatic cell line SW620, were analyzed and the potential targets
      related to tumorigenesis and metastatic progression were investigated. We found
      that 25 miRNAs had been up-regulated and 5 miRNAs had been down-regulated in
      exosomes purified from SW620 culture supernatant. Candidate miRNAs were further
      evaluated for CRC diagnosis using quantitative real-time polymerase chain
      reaction in CRC patients. Higher expression levels of circulating exosomal miR-17
      5p and miR-92a-3p were significantly associated with pathologic stages and grades
      of the CRC patients. CONCLUSIONS: Circulating exosomal miR-17-5p and miR-92a-3p
      may provide a promising noninvasive prognostic biomarker for primary and
      metastatic CRC.

PMID- 29367071
TI  - Joint effects of nine antidepressants on Raphidocelis subcapitata and Skeletonema
      marinoi: A matter of amine functional groups.
AB  - Antidepressants are among the most prescribed pharmaceuticals throughout the
      world. Their presence has already been detected in several aquatic ecosystems
      worldwide and their effects on non-target organisms justify the growing concern
      of both the public and regulatory authorities. These emerging pollutants do not
      occur as isolated compounds but rather as multi-component mixtures, which may
      lead to increased adverse effects compared to individual compounds. Freshwater
      and marine algae seem particularly sensitive to pharmaceuticals, including
      antidepressants. Studies assessing the toxicity of antidepressant mixture to
      algae focused mainly on binary mixtures of selective serotonin reuptake
      inhibitors. In the present experiment, the freshwater algae Raphidocelis
      subcapitata (formerly known as Pseudokirchneriella subcapitata) and the marine
      diatom Skeletonema marinoi were exposed to equitoxic mixtures of 9
      antidepressants (fluvoxamine, fluoxetine, sertraline, duloxetine, venlafaxine,
      clomipramine, amitriptyline, and citalopram) at different concentrations. The
      growth inhibition was measured. Results showed that the toxicity of this mixture
      was higher than the effects of each individual component, highlighting simple
      additivity or synergistic effects, whereas tested concentrations were below the
      10% inhibition concentration (IC10) of each compound. Moreover, the QSAR analysis
      highlighted that antidepressants would act through narcosis (non-specific mode of
      action) towards the two species of algae. However, more specific effects can be
      observed by differentiating compounds with a primary/secondary amine from those
      with a tertiary amine. These mixture effects on algal species have to be
      assessed, especially since any impacts on phytoplankton could ultimately impact
      higher trophic levels (less food, secondary poisoning).

PMID- 29367072
TI  - The effects of elevated environmental CO2 on nitrite uptake in the air-breathing
      clown knifefish, Chitala ornata.
AB  - Nitrite and carbon dioxide are common environmental contaminants in the intensive
      aquaculture ponds used to farm clown knifefish (Chitala ornata) in the Mekong
      delta, Vietnam. Here we tested the hypothesis that hypercapnia reduces nitrite
      uptake across the gills, because pH regulation will reduce chloride uptake and
      hence nitrite uptake as the two ions compete for the same transport route via the
      branchial HCO3-/Cl- exchanger. Fish fitted with arterial catheters were exposed
      to normocapnic/normoxic water (control), nitrite (1 mM), hypercapnia (21 mmHg
      CO2), or combined hypercapnia (acclimated hypercapnia) and nitrite for 96 h.
      Blood was sampled to measure acid-base status, haemoglobin derivatives and plasma
      ions. Plasma nitrite increased for 48 h, but levels stayed below the exposure
      concentration, and subsequently decreased as a result of nitrite detoxification
      to nitrate. The total uptake of nitrite (evaluated as [NO2-] + [NO3-]) was
      significantly decreased in hypercapnia, in accordance with the hypothesis.
      Methemoglobin and nitrosylhemoglobin levels were similarly lower during
      hypercapnic compared to normocapnic nitrite exposure. The respiratory acidosis
      induced by hypercapnia was half-compensated by bicarbonate accumulation in 96 h,
      which was mainly chloride-mediated (i.e. reduced Cl- influx via the branchial
      HCO3-/Cl- exchanger). Plasma osmolality and main ions (Na+, Cl-) were
      significantly decreased by hypercapnia and by nitrite exposure, consistent with
      inhibition of active transport. We conclude that hypercapnia induces a long
      lasting, and mainly chloride-mediated acid-base regulation that reduces the
      uptake of nitrite across the gills.

PMID- 29367073
TI  - "This body is me": Discovering the ways in which the body is salient in people's
      identities.
AB  - Although previous research has revealed associations between negative body image
      and identity problems, there are sound theoretical reasons to assume much greater
      diversity in relations between body image and identity. The aim of the present
      qualitative study was to explore the ways people find the body salient to their
      identities. Young adults (N=121; 51% women) were interviewed, and four main
      themes were found: identification with the body, body functionality in identity
      relevant tasks, appearance and identity in social interactions, and identity
      relevant bodily engagement. Both positive and negative ways in which the body is
      salient in identity were described and descriptions included functionality,
      embodied experiences, and social environments. Gender differences were not found
      with one exception: more women than men described experiences of identifying with
      their bodies. These novel results have implications for the understanding of the
      interconnection between body image and identity and may open avenues for
      continued research.

PMID- 29367074
TI  - Self-objectification, weight bias internalization, and binge eating in young
      women: Testing a mediational model.
AB  - Self-objectification and weight bias internalization are two internalization
      processes that are positively correlated with binge eating among young women.
      However, the mechanisms underlying these relationships are understudied.
      Consistent with objectification theory, this study examined appearance anxiety
      and body shame as mediators between self-objectification, weight bias
      internalization and binge eating. Female undergraduates (N=102) completed self
      report measures of self-objectification, weight bias internalization, appearance
      anxiety, body shame, and binge eating. Results indicated that women who self
      objectified and internalized negative weight-related attitudes reported greater
      binge eating (rs=.43 and rs=.57, respectively) and these associations were
      mediated by the combined effects of body shame and appearance anxiety. The
      contrast between the two mediators was also significant, such that body shame
      emerged as a stronger mediator within both mediational models. Results
      demonstrated that these internalization processes contribute to negative affect
      in young women, which may in turn lead to binge eating.

PMID- 29367075
TI  - The effect of functionality-focused and appearance-focused images of models of
      mixed body sizes on women's state-oriented body appreciation.
AB  - Research demonstrates that exposure to appearance-focused images of models
      depicting societal standards of beauty negatively affect women's state-oriented
      body dissatisfaction. The purpose of this research was to extend this
      experimental research to women's state-oriented body appreciation. The 374 women
      participants were randomly assigned to view images that were either depicting a
      model who was representative or not representative of the thin ideal (body size),
      while this model was in either an appearance-focused pose or a function-oriented
      pose (pose type). State body appreciation increased significantly after viewing
      images depicting models who did not conform to societal standards of thinness
      (p<0.001). Exposure to the control condition images, which were images of natural
      environments, also produced increases in state body appreciation (p=0.049). These
      findings provide insight into the construct of state body appreciation and offer
      implications for future positive body image research.

PMID- 29367076
TI  - Angiotensin peptides in the non-gravid uterus: Paracrine actions beyond
      circulation.
AB  - The renin-angiotensin system (RAS) involves a complex network of precursors,
      peptides, enzymes and receptors comprising a systemic (endocrine) and a local
      (paracrine/autocrine) system. The local RAS plays important roles in tissue
      modulation and may operate independently of or in close interaction with the
      circulatory RAS, acting in a complementary fashion. Angiotensin (Ang) II, its
      receptor AT1 and Ang-(1-7) expression in the endometrium vary with menstrual
      cycle, and stromal cell decidualization in vitro is accompanied by local
      synthesis of angiotensinogen and prorenin. Mas receptor is unlikely to undergo
      marked changes accompanying the cyclic ovarian steroid hormone fluctuations.
      Studies investigating the functional relevance of the RAS in the non-gravid
      uterus show a number of paracrine effects beyond circulation and suggest that RAS
      peptides may be involved in the pathophysiology of proliferative and fibrotic
      diseases. Endometrial cancer is associated with increased expression of Ang II,
      Ang-converting enzyme 1 and AT1 in the tumoral tissue compared to neighboring non
      neoplastic endometrium, and also with a gene polymorphism that enhances AT1
      signal. Ang II induces human endometrial cells to transdifferentiate into cells
      with myofibroblast phenotype and to synthetize extracellular matrix components
      that might contribute to endometrial fibrosis. Altogether, these findings point
      to a fully operating RAS within the uterus, but since many concepts rely on
      preliminary evidence further studies are needed to clarify the role of the local
      RAS in uterine physiology and pathophysiology.

PMID- 29367077
TI  - Synthesis, anticancer assessment on human breast, liver and colon carcinoma cell
      lines and molecular modeling study using novel pyrazolo[4,3-c]pyridine
      derivatives.
AB  - The key intermediate 3-aminopyrazolo[4,3-c]pyridine-4,6-dione (2) is considered
      as a precursor for some novel pyrazolo[4,3-c]pyridines 4a-c,
      arylhydrazopyrazolo[4,3-c]pyridines 8a-e, pyrazolo[4,5,1-ij][1,6]naphthyridines
      11a-e and pyrido[4',3':3,4]pyrazolo[1,5-a]-pyrimidines 15a-d through Knovenegal
      condensation, coupling reaction and Michael addition. Some of the newly
      synthesized pyrazolo[4,3-c]pyridine derivatives were investigated for anticancer
      activity. The results of the cytotoxic activity revealed that compound 6b was the
      most active compound against the breast and liver carcinoma cell lines which
      gives IC50 values of 1.937 and 3.695 ug/mL, respectively compared to reference
      drug (doxorubicin) with IC50 values of 2.527 and 4.749 ug/ml, respectively.
      Moreover, compound 6c was potent compound against the colon carcinoma cell line
      which gives the value of IC50 = 2.914 ug/ml compared to doxorubicin with IC50
      value of 3.641 ug/ml. Some selected of the novel synthesized compounds were
      docked inside the active site of ERK2 enzyme and were found display a suitable
      binding with the active site amino acids according to their bond lengths, angles
      and conformational energy.

PMID- 29367078
TI  - Influence of the d/l configuration of N-acyl-homoserine lactones (AHLs) and
      analogues on their Lux-R dependent quorum sensing activity.
AB  - Whereas l-3-oxo-hexanoyl homoserine lactone (OHHL) is the active enantiomer of
      the of LuxR-regulated quorum sensing (QS) autoinducer, its d isomer is implicitly
      considered as inactive. The present work aims to clarify this l-specificity and
      investigate whether it extends to some analogues in the acyl homoserine lactone
      (AHL) family. For this purpose, OHHL and a series of AHL analogs were synthesized
      in racemic and enantiomerically pure d and l forms and their ability to induce or
      attenuate bioluminescence in the LuxR-dependent QS system was evaluated. In this
      study, l-isomers are confirmed as either the only, or as the most active,
      enantiomers. However, in several cases, especially for the natural ligand of LuxR
      (OHHL) and the very similar AHL agonist analogue 2, the d-isomer cannot be
      considered as totally inactive on QS. Molecular modelling suggests that when the
      lactone moiety of the d-isomer is able to twist, enabling the lactone carbonyl
      group and the amide function to interact with the key residues in the binding
      site, then the d-isomer can exhibit some activity.

PMID- 29367079
TI  - Synthesis and structure-activity relationship study of multi-target triazine
      derivatives as innovative candidates for treatment of Alzheimer's disease.
AB  - The complex pathogenesis of Alzheimer's disease (AD) requires using multi-target
      ligands (MTLs) for disease management. We synthesized, characterized and
      evaluated a series of novel triazine analogues as MTLs for AD. The biological
      screening results indicated that most of our compounds displayed potent
      inhibitory activities against beta-site APP-cleaving enzyme 1 (BACE1) using a
      FRET-based assay. Compounds 6c and 6m were found to possess significant BACE1
      inhibitory properties with IC50 values of 0.91 (+/-0.25) uM and 0.69 (+/-0.20)
      uM, respectively. DPPH radical scavenging activity evaluation showed that
      compounds with hydroxyl and pyrrole moieties had antioxidant effects. Docking
      evaluations provided insight into enzyme inhibitory interactions of novel
      synthesized compounds with the BACE1 active site involving a critical role for
      Gln73 and/or Phe108 alongside of Asp32. Metal chelation tests confirmed that
      compound 6m is a chelator for Fe2+, Fe3+, Zn2+, Cu2+. Moreover 6m as the most
      potent BACE1 inhibitor did not show any toxicity against PC12 neuronal cells.
      These findings demonstrate the high potential of triazine scaffolds in the design
      of MTLs for treatment of AD.

PMID- 29367080
TI  - Human IgG lacking effector functions demonstrate lower FcRn-binding and reduced
      transplacental transport.
AB  - We have previously generated human IgG1 antibodies that were engineered for
      reduced binding to the classical Fcgamma receptors (FcgammaRI-III) and C1q,
      thereby eliminating their destructive effector functions (constant region
      G1Deltanab). In their potential use as blocking agents, favorable binding to the
      neonatal Fc receptor (FcRn) is important to preserve the long half-life typical
      of IgG. An ability to cross the placenta, which is also mediated, at least in
      part, by FcRn is desirable in some indications, such as feto-maternal alloimmune
      disorders. Here, we show that G1Deltanab mutants retain pH-dependent binding to
      human FcRn but that the amino acid alterations reduce the affinity of the
      IgG1:FcRn interaction by 2.0-fold and 1.6-fold for the two antibodies
      investigated. The transport of the modified G1Deltanab mutants across monolayers
      of human cell lines expressing FcRn was approximately 75% of the wild-type,
      except that no difference was observed with human umbilical vein endothelial
      cells. G1Deltanab mutation also reduced transport in an ex vivo placenta model.
      In conclusion, we demonstrate that, although the G1Deltanab mutations are away
      from the FcRn-binding site, they have long-distance effects, modulating FcRn
      binding and transcellular transport. Our findings have implications for the
      design of therapeutic human IgG with tailored effector functions.

PMID- 29367081
TI  - Immune modulatory properties of 6-gingerol and resveratrol in Atlantic salmon
      macrophages.
AB  - The innate immune system provides the first barrier to infection and disease
      through various processes including activation of inflammation. Inflammation is a
      biological process whereby immune cells, including macrophages, respond to, and
      work together to eliminate, damage from injury and disease. Chronic or sustained
      inflammation, however, can be detrimental to the health and growth of animals,
      including fish. Immune modulating functional plant compounds, supplemented as
      feed additives, may be safe and natural approaches to controlling inflammation
      and disease. This project employed an in vitro cell model to assess the effect of
      two plant phytoextracts, 6-gingerol and resveratrol, on Atlantic salmon
      macrophages. To determine if these plant compounds can modify Atlantic salmon
      macrophage function, primary macrophages were isolated from the head kidney,
      cultured and pre-treated with the compound for 24 hours. The cells were then
      challenged with a bacterial pathogen-associated molecular pattern (PAMP),
      lipopolysaccharide (LPS). To determine if the plant compound pre-treatment
      modifies macrophage response to LPS stimulation, the mRNA expression of anti
      bacterial and cytokine genes (COX2, TNFalpha, IL-1beta, IL-8, Lect-2 and sTLR5)
      was analyzed by real-time quantitative polymerase chain reaction (qPCR). In
      addition, the effects of compound pre-treatment on macrophage ROS production and
      phagocytic responses were analyzed via flow cytometry. We found that both 6
      gingerol and resveratrol modified macrophage function, with 6-gingerol having an
      overall greater effect on expression of the genes analyzed, suggesting that these
      functional plant compounds may be good candidates as feed additives and should be
      investigated further.

PMID- 29367082
TI  - Argatroban dosing in obesity.
AB  - PURPOSE: Obesity is associated with significant alterations in pharmacokinetic
      and pharmacodynamic properties. The use of weight based anticoagulants such as
      argatroban may put obese patients at an increased risk of hemorrhagic events. The
      purpose of this study was to evaluate argatroban dosing requirements in obese vs
      non-obese patients. METHODS: This single-center, retrospective cohort study
      included patients >=18 years with suspected HIT, treated with argatroban for >=12
      h. Patients were stratified by body mass index (BMI) into obese (BMI > 30 kg/m2)
      and non-obese (BMI <= 30 kg/m2) groups. The primary outcome was the median
      maintenance dose required to achieve two consecutive therapeutic activated
      partial thromboplastin times. RESULTS: A total of 121 patients were included. The
      median BMI in the obese vs non-obese groups was 35.8 vs 24.05 kg/m2 (p < .0001).
      Although statistically significant, there was no clinically significant
      difference in median maintenance argatroban dose in obese versus non-obese
      patients (1 vs 1 MUg/kg/min; p = .01). In-hospital major bleeding and in-hospital
      thrombosis also did not differ between the two groups. CONCLUSION: Obese patients
      require similar median argatroban maintenance doses when compared to non-obese
      patients. Based on these results argatroban should be dosed using actual body
      weight regardless of BMI.

PMID- 29367083
TI  - Assessment of two contact activation reagents for the diagnosis of congenital
      factor XI deficiency.
AB  - INTRODUCTION: Congenital FXI deficiency, a coagulopathy associated with low
      bleeding risk but thrombotic protection, is usually diagnosed by prolonged APTT
      and confirmed by coagulation assays. Recent evidences suggest that FXI deficiency
      might be underestimated. Sensitive and reliable methods to detect FXI deficiency
      are required. AIM: To examine the sensitivity of two methods and two contact
      activators on FXI deficiency screening. METHODS: 140 cases with FXI deficiency, 9
      severe and 131 moderate, caused by 11different mutations were recruited. APTT and
      FXI:C were assessed in ACL-TOP 500coagulometer with silica-based (SynthASil) and
      ellagic acid-based (SynthAFax) reagents. F12 rs1801020 SNP was genotyped with
      Taqman probes. RESULTS: Severe FXI deficiency significantly prolonged APTT with
      both reagents. However, a high proportion of moderate deficiencies would not be
      detected using APTT, with false negatives of 22% for SynthASil and 12% for
      SynthAFax. False negatives results mainly corresponded to cases with qualitative
      deficiency (CRM+: p.Pro538Leu), which also had higher FXI coagulant activity.
      Using SynthASil, the common F12 rs1801020 variant, associated to low FXII levels,
      significantly prolonged APTT in moderate FXI deficiency subjects. FXI:C values
      were significantly higher with SynthAFax than with SynthASil (47.7+/-12.7 vs.
      40.4+/-14.9), so SynthAFax rendered higher rate of false negatives than SynthASil
      (7% vs.2%). CONCLUSIONS: Moderate FXI deficiency, particularly CRM+, might be
      underestimated using current diagnostic methods. The activator, FXI and FXII
      levels may contribute to a higher rate of false negatives using APTT. Our results
      suggests that the best screening method for FXI deficiency is FXI:C using silica.

PMID- 29367084
TI  - Generation of a human induced pluripotent stem cell line (MUSIi001-A) from
      caesarean section scar fibroblasts using Sendai viral vectors.
AB  - We generated a human induced pluripotent stem cell (iPSC) line from caesarean
      section scar fibroblasts of a 33-year-old healthy woman using transgene-free
      Sendai viral vectors under feeder-free condition. The established iPSC line,
      designated as MUSIi001-A, exhibited a normal karyotype, expressed pluripotent
      markers, differentiated into cells of three embryonic germ layers. Further
      analyses showed that the Sendai viral genome was absent at passage 25. The
      MUSIi001-A line can serve as a control for studying developmental biology and
      phenotypic comparison with disease-specific iPSCs.

PMID- 29367085
TI  - Serum bone biomarkers osteocalcin and pyridinoline in mares during pregnancy and
      lactation, and in foals during early post-natal life.
AB  - Breeding mares typically foal yearly. Little is known about the dynamics of
      maternal bone stores during gestation and lactation, the timing of any maternal
      bone mobilisation, re-accretion post-foaling, or the dynamics of bone metabolism
      in foals. We measured serum osteocalcin (OC) and serum pyridinoline (PYD)
      concentrations in 18 mares monthly from 6months gestation to foaling, and in both
      mares and foals for 4months after birth. From 6 to 11months of gestation, there
      was no change in mean monthly OC. Serum PYD increased between 7months gestation
      and foaling. After foaling, mean serum OC was low up to 14days, rising to peak at
      1month. Serum PYD rose concomitantly during this period, but subsequently
      declined. The mare OC:PYD ratio fell to a nadir within 14days of birth, before
      rising to a peak at 2months. In foals, OC rose within the first 24h of birth to
      peak at 3months. PYD fell from birth levels by 1month of age. Maternal bone
      mobilisation occurs progressively from 8months of gestation until term, before
      increasing markedly in very early lactation. Net mobilisation switches to
      accretion by one to two months of foaling, suggesting that this is a period
      during which mares replenish their own bone stores. Changes in the ratio of OC to
      PYD indicate adaptation to the prevailing biological milieu. In foals, the
      increase in the OC:PYD ratio in early life reflects the dominance of bone
      accretion.

PMID- 29367086
TI  - Sedation of sheep following the administration of acepromazine with buprenorphine
      or morphine is similar.
AB  - The aim of this study was to compare sedation of sheep with acepromazine and
      buprenorphine or morphine. Twenty merino sheep received acepromazine (0.03mg/kg)
      with buprenorphine (0.02mg/kg, AB, n=10) or morphine (0.3mg/kg, AM, n=10) by
      intramuscular injection. Sedation was scored (SS) on a scale from 0 (no sedation)
      to 10 (heavy sedation). Response to restraint was scored (RS) on a scale from 0
      (agitated) to 4 (relaxed). Three independent blinded observers and a single
      blinded observer determined the SS and RS, respectively. The SSs were summed
      (maximum 30). Data were compared using a t-test. Data is mean+/-SD (95%
      confidence interval). Each group comprised 2 wethers and 8 ewes. There was no
      difference between the AB and AM groups: weight 44+/-3.1kg and 44.7+/-3kg
      (p=0.58); SS 4.6+/-3.2 (2.4-6.9) and 6.6+/-3.5 (4.1-9.1) (p=0.21); and RS 1.6+/
      1.3 (0.5-2.7) and 2+/-1.5 (0.7-3.3) (p=0.6). No adverse effects of the drugs were
      observed. Sedation with AB or AM at these doses is similar in sheep without
      observed adverse effects.

PMID- 29367087
TI  - Mobility of 232Th and 210Po in red mud.
AB  - The valorization of industrial by-products such as red mud became a tempting
      opportunity, but the understanding of the risks involved is required for the safe
      utilization of these products. One of the risks involved are the elevated levels
      of radionuclides (in the 100-1300 Bq/kg range for both the 238U and 232 Th decay
      chains, but usually lower than 1000 Bq/kg, which is the recommended limit for
      excemption or clearance according to the EU BSS released in 2013) in red mud that
      can affect human health. There is no satisfactory answer for the utilization of
      red mud; the main current solution is still almost exclusively disposal into a
      landfill. For the safe utilization and deposition of red mud, it is important to
      be able to assess the leaching behaviour of radionuclides. Because there is no
      commonly accepted measurement protocol for testing the leaching of radionuclides
      in the EU a combined measurement protocol was made and tested based on heavy
      metal leaching methods. The leaching features of red mud were studied by methods
      compliant with the MSZ-21470-50 Hungarian standard, the CEN/TS 14429 standard and
      the Tessier sequential extraction method for 232Th and 210Po. The leached
      solutions were taken to radiochemical separation followed by spontaneous
      deposition for Po and electrodeposition for Th. The 332 +/- 33 Bq/kg 232Th
      content was minimally mobile, 1% became available for distilled water 1% and 6%
      for Lakanen-Ervio solution; the Tessier extraction showed minimal mobility in the
      first four steps, while more than 85% remained in the residue. The 210Po
      measurements had a severe disturbing effect in many cases, probably due to large
      amounts of iron present in the red mud, from the 310 +/- 12 Bq/kg by aqua regia
      digestion, distilled water mobilized 23%, while Lakanen-Ervio solution mobilized
      ~13%. The proposed protocol is suitable for the analysis of Th and Po leaching
      behaviour.

PMID- 29367088
TI  - Sinomenine inhibits fibroblast-like synoviocyte proliferation by regulating
      alpha7nAChR expression via ERK/Egr-1 pathway.
AB  - Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid
      arthritis (RA), and involved in inflammation and joint destruction. Sinomenine
      (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti
      inflammatory and analgesic effect and been used for RA treatment in China. Alpha
      7 nicotinic acetylcholine receptors (alpha7nAChR), as the key receptor in
      cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been
      detected in RA patients synovium, but its role is still unclear. Here we
      investigated the association between the aggressive proliferation of FLS and
      alpha7nAChR expression and the effect of sinomenine. FLS was isolated from
      synovial tissues of adjuvant-induced-arthritis (AIA) rat. Tumor necrosis
      factor(TNF)-alpha was used to induce the aggressive proliferation of FLS. MTT
      assay was applied to evaluate the proliferation of FLS. The messenger RNA (mRNA)
      and protein levels of alpha7nAChR and early growth response gene-1 (Egr-1) were
      measured. The results showed that TNF-alpha induced FLS proliferation in vitro (P
      < .01) and increased the phosphorylation of ERK1/2 and the expression of Egr-1
      and alpha7nAChR (P < .05 or P < .01). U0126, the inhibitor of ERK1/2 inhibited
      alpha7nAChR expression and FLS proliferation significantly (P < .05 or P < .01).
      Specific short interference RNA(siRNA) of alpha7nAChR decreased alpha7nAChR
      expression and inhibited FLS proliferation as well. SIN inhibited the
      proliferation of FLS and decreased the phosphorylation of ERK1/2, and the
      expression of Egr-1 and alpha7nAChR induced by TNF-alpha (P < .05). In
      conclusion, the expression of alpha7nAChR involved in the aggressive
      proliferation of FLS induced by TNF-alpha and was regulated by ERK/Egr-1 signal
      pathway. SIN inhibited FLS proliferation and alpha7nAChR expression through
      inhibiting ERK/Egr-1 signal pathway, this may contribute to the anti-inflammatory
      and anti-arthritic effect of SIN.

PMID- 29367089
TI  - Cortisol inhibits NF-kappaB and MAPK pathways in LPS activated bovine endometrial
      epithelial cells.
AB  - The bovine uterus is subject to infection after calving, which may lead to
      endometritis. Elevated cortisol levels have been observed in postpartum cattle.
      However, the role of cortisol in the inflammatory response of the uterus has not
      been reported. The aim of this study was to investigate the anti-inflammatory
      effects of cortisol on lipopolysaccharide (LPS)-induced primary bovine
      endometrial epithelial cells (BEECs). BEECs were treated with various
      concentrations of cortisol (5, 15 and 30 ng/mL) in the presence of LPS. The mRNA
      expression of TLR4 and proinflammatory cytokines was measured with qPCR. The
      activation of NF-kappaB and MAPK signalling pathways was detected with Western
      blotting and immunofluorescence. Cortisol induced the down-regulation of the mRNA
      expression of toll-like receptor 4 (TLR4) and proinflammatory cytokines,
      including interleukin (IL)-1beta, IL-6, IL-8, tumour necrosis factor-alpha (TNF
      alpha), cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS). Cortisol
      inhibited the activity of nuclear factor-kappaB (NF-kappaB) via blocking the
      phosphorylation and degradation of IkappaB. Cortisol suppressed the
      phosphorylation of mitogen-activated protein kinase (MAPK), including
      extracellular signal-regulated kinase (ERK1/2), p38MAPK and c-Jun N-terminal
      kinase/stress-activated protein kinase (JNK). These results demonstrated that
      cortisol may exert its anti-inflammatory actions by regulating NF-kappaB
      activation and MAPK phosphorylation.

PMID- 29367090
TI  - Inhibition of NF-kappaB pathway in fibroblast-like synoviocytes by alpha
      mangostin implicated in protective effects on joints in rats suffering from
      adjuvant-induced arthritis.
AB  - alpha-Mangostin (MG) is a bioactive compound isolated from mangosteen. This study
      was aimed to investigate effects of MG on adjuvant-induced arthritis (AA) in rats
      and decipher the underlying mechanisms. Clinical severity of AA was evaluated by
      paw oedema, arthritis score, and hematological parameters. Digital radiography
      (DR) and histological examinations were employed to assess joints destructions.
      Immune functions were evaluated by T cell subsets distribution. Effects on NF
      kappaB pathway were investigated by immunohistochemical, western-blot and
      immunofluorescence methods both in vivo and vitro. It was found MG possessed
      superior anti-inflammatory effects in vivo, suggested by attenuated paw swelling,
      reduced inflammatory cells infiltration and decreased the secretion of TNF-alpha
      and IL-1beta in serum. Meanwhile MG inhibited fibrous hyperplasia, synovial
      angiogenesis, cartilage and bone degradation in AA rats. Although MG exerted
      little effects on CD4+ population, it greatly decreased IFN-gamma positive cells
      and promoted expression of FOXP3 in immune organs, indicating restoration of
      Th1/Treg cells ratio and recovery of immune homeostasis in vivo. Inhibition of NF
      kappaB induced by MG was indicated by reduced the expression of p-p65 and VEGF in
      synovium. In vitro experiments found MG at 10 MUg/ml significantly suppressed the
      expression and phosphorylation of key proteins implicated in NF-kappaB pathway
      and inhibited nucleus translocation of p65. These changes led to increased
      apoptosis and proliferation inhibition of HFLS-RA cells. The results demonstrated
      regulation of immune functions was deeply involved in the therapeutic actions of
      MG on AA, and it's inhibition on NF-kappaB in fibroblast-like synoviocytes was
      associated to the protective effects on joints.

PMID- 29367091
TI  - Chrysophanol demonstrates anti-inflammatory properties in LPS-primed RAW 264.7
      macrophages through activating PPAR-gamma.
AB  - Sepsis is a life-threatening disease. Inflammation is a major concomitant symptom
      of sepsis Chrysophanol, an anthraquinone derivative isolated from the rhizomes of
      rheumpalmatum, has been reported to have a protective effect against
      lipopolysaccharide(LPS)-induced inflammation. However, the underlying molecular
      mechanisms are not well understood. The aim of this study was to explore the
      effect and mechanism of chrysophanol on lipopolysaccharide (LPS)-induced anti
      inflammatory effect of RAW264.7 cells and its involved potential mechanism. The
      mRNA and protein expression of tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-1beta and inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF
      kappaB) and PPAR-gamma were measured by qRT-PCR and western blotting, the
      production of TNF-alpha, IL-1beta was evaluated by ELISA. Then, the
      phosphorylation of NF-kappaB p65 was also detected by western blotting. And NF
      kappaB p65 promoter activity was analyzed by the Dual-Luciferase reporter assay
      system as well. Meanwhile, PPAR-gamma inhibitor GW9662 was performed to knockdown
      PPAR-gamma expression in cells. Our data revealed that LPS induced the up
      regulation of TNF-alpha, IL-1beta, iNOS and NF-kappaB p65, the down-regulation of
      PPAR-gamma were substantially suppressed by chrysophanol in RAW264.7 cells.
      Furthermore, our data also figured out that these effects of chrysophanol were
      largely abrogated by PPAR-gamma inhibitor GW9662. Taken together, our results
      indicated that LPS-induced inflammation was potently compromised by chrysophanol
      very likely through the PPAR-gamma-dependent inactivation of NF-kappaB in
      RAW264.7 cells.

PMID- 29367092
TI  - Paralysis without face mask test ventilation - Implications for the management of
      unexpected airway difficulties.

PMID- 29367093
TI  - A mini-fluid challenge of 150mL predicts fluid responsiveness using ModelflowR
      pulse contour cardiac output directly after cardiac surgery.
AB  - STUDY OBJECTIVE: The mini-fluid challenge may predict fluid responsiveness with
      minimum risk of fluid overloading. However, the amount of fluid as well as the
      best manner to evaluate the effect is unclear. In this prospective observational
      pilot study, the value of changes in pulse contour cardiac output (CO)
      measurements during mini-fluid challenges is investigated. DESIGN: Prospective
      observational study. SETTING: Intensive Care Unit of a university hospital.
      PATIENTS: Twenty-one patients directly after elective cardiac surgery on
      mechanical ventilation. INTERVENTIONS: The patients were subsequently given 10
      intravenous boluses of 50mL of hydroxyethyl starch with a total of 500mL per
      patient while measuring pulse contour CO. MEASUREMENTS: We measured CO by minimal
      invasive ModelflowR (COm) and PulseCOR (COli), before and one minute after each
      fluid bolus. We analyzed the smallest volume that was predictive of fluid
      responsiveness. A positive fluid response was defined as an increase in CO of
      >10% after 500mL fluid infusion. MAIN RESULTS: Fifteen patients (71%) were COm
      responders and 13 patients (62%) COli responders. An increase in COm after 150mL
      of fluid >5.0% yielded a positive and negative predictive value (+PV and -PV) of
      100% with an area under the curve (AUC) of 1.00 (P<0.001). An increase in COli
      >6.3% after 200mL was able to predict a fluid response in COli after 500mL with a
      +PV of 100% and -PV of 73%, with an AUC of 0.88 (P<0.001). CONCLUSION: The use of
      minimal invasive ModelflowR pulse contour CO measurements following a mini-fluid
      challenge of 150mL can predict fluid responsiveness and may help to improve fluid
      management.

PMID- 29367094
TI  - Bacitracin irrigation leading to anaphylaxis and cardiovascular collapse in the
      ambulatory surgery center setting.

PMID- 29367095
TI  - Re(CO)3([18F]FEDA), a novel 18F PET renal tracer: Radiosynthesis and preclinical
      evaluation.
AB  - INTRODUCTION: Our previous work demonstrated that the 99mTc renal tracer,
      99mTc(CO)3(FEDA) (99mTc-1), has a rapid clearance comparable in rats to that of
      131I-OIH, the radioactive gold standard for the measurement of effective renal
      plasma flow. The uncharged fluoroethyl pendant group of 99mTc-1 provides a route
      to the synthesis of a structurally analogous rhenium-tricarbonyl 18F renal
      imaging agent, Re(CO)3([18F]FEDA) (18F-1). Our goal was to develop an efficient
      one-step method for the preparation of 18F-1 and to compare its pharmacokinetic
      properties with those of 131I-OIH in rats. METHODS: 18F-1 was prepared by the
      nucleophilic 18F-fluorination of its tosyl precursor. The labeled compound was
      isolated by HPLC and subsequently evaluated in Sprague-Dawley rats using 131I-OIH
      as an internal control and by dynamic PET/CT imaging. Plasma protein binding
      (PPB) and erythrocyte uptake (RCB) were determined and the urine was analyzed for
      metabolites. RESULTS: 18F-1 was efficiently prepared as a single species with
      high radiochemical purity (>99%) and it displayed high radiochemical stability in
      vitro and in vivo. PPB was 87% and RCB was 21%. Biodistribution studies confirmed
      rapid renal extraction and high specificity for renal excretion, comparable to
      that of 131I-OIH, with minimal hepatic/gastrointestinal elimination. The activity
      in the urine, as a percentage of 131I-OIH, was 92% and 95% at 10 and 60 min,
      respectively. All other organs (heart, spleen, lungs) showed a negligible tracer
      uptake (<0.4% ID). Dynamic microPET/CT imaging demonstrated rapid transit of 18F
      1 through the kidneys and into the bladder; there was no demonstrable activity in
      bone verifying the absence of free [18F]fluoride. CONCLUSIONS: 18F-1 exhibited a
      high specificity for the kidney, rapid renal excretion comparable to that of 131I
      OIH and high in vivo radiochemical stability. Not only is 18F-1 a promising PET
      renal tracer, but it provides a route to the development of a pair of analogous
      18F/99mTc renal imaging agents with almost identical structures and comparable
      pharmacokinetic properties. These promising in vivo results warrant subsequent
      evaluation in humans.

PMID- 29367096
TI  - Molecular imaging of platelet-derived growth factor receptor-alpha (PDGFRalpha)
      in papillary thyroid cancer using immuno-PET.
AB  - INTRODUCTION: Receptor tyrosine kinase (RTK) platelet-derived growth factor
      receptor-alpha (PDGFRalpha) was recently identified as a molecular switch for
      dedifferentiation in thyroid cancer that predicts resistance to therapy as well
      as recurrence of disease in papillary thyroid cancer. Here we describe the
      radiolabeling and functional characterization of an imaging probe based on a
      PDGFRalpha-specific monoclonal antibody (mAb) for immuno-PET imaging of
      PDGFRalpha in papillary thyroid cancer. METHODS: Antibody D13C6 (Cell Signaling)
      was decorated with chelator NOTA using bioconjugation reaction with 2-(p-NCS-Bz)
      NOTA. Radiolabeling was carried out using 40 MUg of antibody-NOTA conjugate with
      143-223 MBq of [64Cu]CuCl2 in 0.25 M NaOAc (pH 5.5) at 30  degrees C for 1 h. The
      reaction mixture was purified with size-exclusion chromatography (PD-10 column).
      PDGFRalpha and mock transfected B-CPAP thyroid cancer cells lines for validation
      of 64Cu-labeled immuno-conjugates were generated using LVX-Tet-On technology. PET
      imaging was performed in NSG mice bearing bilaterally-induced PDGFRalpha (+/-) B
      CPAP tumors. RESULTS: Bioconjugation of NOTA chelator to monoclonal antibody
      D13C6 resulted in 2.8 +/- 1.3 chelator molecules per antibody as determined by
      radiometric titration with 64Cu. [64Cu]Cu-NOTA-D13C6 was isolated in high
      radiochemical purity (>98%) and good radiochemical yields (19-61%). The specific
      activity was 0.9-5.1 MBq/MUg. Cellular uptake studies revealed a specific
      radiotracer uptake in PDGFRalpha expressing cells compared to control cells. PET
      imaging resulted in SUVmean values of ~5.5 for PDGFRalpha (+) and ~2 for
      PDGFRalpha (-) tumors, after 48 h p.i.. After 1 h, radiotracer uptake was also
      observed in the bone marrow (SUVmean ~5) and spleen (SUVmean ~8.5). CONCLUSION:
      Radiolabeled antibody [64Cu]Cu-NOTA-D13C6 represents a novel and promising
      radiotracer for immuno-PET imaging of PDGFRalpha in metastatic papillary thyroid
      cancer. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: The presented
      work has the potential to allow physicians to identify papillary thyroid cancer
      patients at risk of metastases by using the novel immuno-PET imaging assay based
      on PDGFRalpha-targeting antibody [64Cu]Cu-NOTA-D13C6.

PMID- 29367097
TI  - Children's trauma-related symptoms following complex trauma exposure: Evidence of
      gender differences.
AB  - Complex trauma exposure has been operationalized as multiple or chronic
      interpersonal traumas that begin early in life and is thought to result in
      widespread self-regulation difficulties across several domains of functioning.
      Prior research has demonstrated that there are gender differences in trauma
      exposure as well as trauma-related symptoms; however, gender discrepancies have
      not previously been examined in the context of child survivors of complex trauma.
      The aim of the present study was to determine whether there are gender
      differences in both caregiver and child-reported trauma exposure and symptoms
      among 167 children who have experienced complex trauma (3-18 years, M = 9.90, SD
      = 3.92; 61.67% female). Male children were somewhat more likely to have been
      exposed to domestic violence, while female children were more likely to have
      experienced sexual abuse as well as more likely to have been abused by a
      caregiver. Gender differences were observed for several of the caregiver-reported
      symptom domains, with female children exhibiting higher levels of depression,
      dissociation, posttraumatic stress disorder (PTSD) hyperarousal symptoms, and
      total PTSD symptoms. Female children also self-reported higher levels of sexual
      concerns, and marginally more re-experiencing and total PTSD symptoms. Secondary
      analyses utilizing only children who experienced sexual abuse revealed that
      gender differences largely remained, again with females manifesting higher levels
      of symptoms. Thus, following complex trauma, female children may be at higher
      risk for trauma-related difficulties, which has implications for research and
      clinical interventions.

PMID- 29367098
TI  - Developing a tailored substance use intervention for youth exiting foster care.
AB  - Youth who are aging out of the foster care system face significant barriers to
      accessing substance use treatment. Mobile interventions have shown efficacy for
      several mental and physical health issues and may be helpful in overcoming
      barriers facing foster youth with substance use problems. A program (iHeLP) for
      substance use reduction was developed that used a computerized screening and
      brief intervention (SBI) followed by six months of dynamically-tailored text
      messages. The program was shown to focus groups of youth (N = 24) ages 18-19 who
      recently left foster care and had moderate to severe substance use risk. Focus
      group feedback was used to modify iHeLP prior to delivery in an open trial (N =
      16). Both study phases included assessments of feasibility and acceptability; the
      open trial also included assessments of substance use outcomes at 3 and 6 months.
      Focus groups indicated a high level of acceptability for the proposed
      intervention components. Of those screened for the open trial, 43% were eligible
      and 74% of those eligible enrolled, indicating good feasibility. Retention
      through the final follow-up was 59%, and drop out was associated with involvement
      in the criminal justice system. Participant ratings for liking, ease of working
      with, interest in and respectfulness of the SBI were high. Satisfaction ratings
      for the texting component were also high. A computerized brief screening
      intervention for substance use risk reduction together with tailored text
      messaging is both feasible and highly acceptable among youth who have recently
      aged-out of foster care.

PMID- 29367099
TI  - Mid-gestational changes in cervicovaginal fluid cytokine levels in asymptomatic
      pregnant women are predictive markers of inflammation-associated spontaneous
      preterm birth.
AB  - OBJECTIVES: Perturbation of the choriodecidual space before the onset of
      spontaneous preterm birth (sPTB) could lead to a concomitant rise in both
      cervicovaginal fluid (CVF) cytokine and fetal fibronectin (FFN), and assessing
      the concentrations of both markers could improve the prediction of sPTB (delivery
      before 37 completed weeks of gestation). Therefore, we prospectively determined
      mid-trimester changes in CVF cytokine and FFN concentrations, and their
      predictive capacity for sPTB in asymptomatic pregnant women. STUDY DESIGN: CVF
      collected at 20+0-22+6 weeks (n = 47: Preterm-delivered = 22, Term-delivered =
      25) and 26+0-28+6 weeks (n = 50: Preterm-delivered = 17, Term-delivered = 33)
      from 63 asymptomatic pregnant women at risk of sPTB were examined. Cytokine and
      FFN concentrations were determined by multiplexed bead-based immunoassay and 10Q
      Rapid analysis (Hologic, MA, USA) respectively. The 20+0-22+6/26+0-28+6 weeks
      ratios of cytokines and FFN concentrations were compared between preterm- and
      term-delivered women using Receiver Operating Characteristics curves to predict
      sPTB. Also, bacterial 16S rDNA from 64 samples (20+0-22+6 weeks n = 36, 26+0-28+6
      weeks n = 28) was amplified by polymerase chain reaction to determine
      associations between vaginal microflora, cytokine and FFN concentrations.
      RESULTS: Changes in RANTES and IL-1beta concentrations between 20+0-22+6 and 26+0
      28+6 weeks, expressed as a ratios, were predictive of sPTB, RANTES (AUC = 0.82,
      CI = 0.62-0.94) more so than IL-1beta (AUC = 0.71, CI = 0.53-0.85) and FFN (not
      predictive). Combining these markers (AUC = 0.83, CI = 0.63-0.95) showed similar
      predictive capacity as RANTES alone. FFN concentrations at 26+0-28+6 weeks
      correlated with IL-1beta (r = 0.4, P = 0.002) and RANTES (r = 0.3, P = 0.03). In
      addition, there was increased prevalence of vaginal anaerobes including
      Bacteroides, Fusobacterium and Mobiluncus between gestational time points in
      women who experienced sPTB compared to the term women (P = 0.0006). CONCLUSIONS:
      CVF RANTES and IL-1beta in mid-trimester of pregnancy correlate with quantitative
      FFN. The levels of CVF RANTES and IL-1beta decline significantly in women who
      deliver at term unlike women who deliver preterm. This observation suggests that
      sPTB may be characterised by sustained choriodecidual inflammation and may have
      clinical value in serial screening for sPTB if confirmed by larger studies.

PMID- 29367100
TI  - Expression levels of interferon-gamma and type 2 deiodinase in patients diagnosed
      with recurrent depressive disorders.
AB  - BACKGROUND: Thyroid hormones (TH) are involved in modulation of the immune system
      and inflammation. TH dysregulation is associated with depressive disorders. The
      iodothyronine deiodinases (DIOs), the key enzymes for TH synthesis, can be
      affected and induced by pro-inflammatory cytokines. We aimed to investigate the
      levels of and correlation between type 2 DIO (DIO2) and interferon-gamma (IFN
      gamma) in patients with recurrent depressive disorders (rDD). METHODS: Data from
      91 rDD patients and 105 healthy controls were analyzed. The diagnoses are based
      on the ICD-10 criteria (F33.0-F33.8). Expression levels of DIO2 and IFN-gamma
      were estimated using the method based on the polymerase chain reaction and the
      enzyme-linked immunosorbent assay (ELISA). RESULTS: The DIO2 expression on
      mRNA/protein levels in rDD patients (both female and males) was reduced as
      compared with the control subjects. No correlation between DIO2 and IFN-gamma
      expression was observed. CONCLUSION: This is the first study to reveal that one
      may cautiously suggest that DIO2 may be involved in the development and/or
      progression of rDD. The mechanisms of TH regulation on depression, however, need
      further investigation.

PMID- 29367101
TI  - Neuroprotective action and mechanistic evaluation of protodioscin against rat
      model of Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is the most widespread motor-affecting
      disease affecting majorly middle- and late age population. Thus, in the current
      study, we intended to explore the neuroprotective effect of protodioscin (Proto)
      against 6-hydroxydopamine (6-OHDA)-induced PD rat model. METHODS: After induction
      of PD with the injection of 6-OHDA, the different dose of Proto was administered
      for the duration of experimental protocol (2 months). We have scrutinized the
      consequence of Proto on the cognitive behaviours via Moris water maze (MWM), and
      recognition of novel objects and its location tasks. The effect of Proto was also
      investigated on the expression of Nrf2 in human neuroblastoma SHSY5Y cells via
      western blot analysis. RESULTS: The results showed significant decrease in
      travelled distance as compared by the lesion treated group. Further significant
      difference was revealed in the latency time to detect the platform that is
      visible and it confirmed that, there were no noteworthy dissimilarity was
      observed in the visual and motor function ability. The result also suggests that,
      the activation of Nrf2 is the possible mechanism of neuroprotection of Proto
      against PD. CONCLUSION: As a concluding remark, the present study confirmed the
      neuroprotective role of Proto against PD both in in vitro and in vivo models.

PMID- 29367102
TI  - Effects of prasugrel on membrane potential and contractile activity of rat
      ventricular myocytes.
AB  - BACKGROUND: Though prasugrel is one of the important P2Y12 inhibitors currently
      in use for antiplatelet therapy, its potential effects on contractility and
      electrical activity of ventricular myocytes have not yet been investigated. Hence
      this study was designed to study the impact of prasugrel on contractile function
      and membrane potential of isolated ventricular myocytes. METHODS: Freshly
      isolated rat ventricular myocytes were used in this study. Myocyte contraction
      was measured during electrical stimulation of cardiomyocytes and the action
      potential (AP) recordings were obtained with current clamp mode of the patch
      clamp amplifier. RESULTS: AP duration and fractional shortening of ventricular
      myocytes did not show any change with the administration of 1MUM of prasugrel.
      However, remarkable depolarization of resting membrane potential followed by
      apparent fibrillation episodes was detected in the cardiomyocytes. Similar events
      were observed in the contractile activity of myocytes during field stimulation.
      Also, a higher concentration of prasugrel (10MUM) elicited repeated
      fibrillations, which disappeared after washout or nitric oxide synthase (NOS)
      inhibition with L-NAME. In contrast, the same concentration of ticagrelor,
      another P2Y12 inhibitor did not induce fibrillation events though it decreased
      the contractility of ventricular myocytes significantly. The perfusion of
      ventricular myocytes with L-NAME did not alter the negative inotropic effect of
      ticagrelor. CONCLUSIONS: Prasugrel, a widely used antithrombotic agent, may
      induce depolarization in the membrane potential of myocytes as well as
      fibrillation via NO mediated pathway.

PMID- 29367103
TI  - Forskolin convalesces memory in high fat diet-induced dementia in wistar rats
      Plausible role of pregnane x receptors.
AB  - BACKGROUND: Studies have signified that high serum cholesterol plays an
      intriguing role in amyloid beta metabolism and accumulation. Ligand activation of
      pregnane x receptors (PXRs), up-regulates the expression of P- glycoprotein and
      has a crucial role in amyloid beta efflux. The present study has been undertaken
      to investigate the effect of forskolin, a PXR agonist in experimental dementia.
      METHODS: Wistar rats were allowed free access to cholesterol-rich High Fat Diet
      (HFD) for 90days to induce dementia. HFD rats were then treated with forskolin
      (10mg/kg; 20mg/kg) followed by exposure to Morris water maze (MWM) test to
      deconvolute the mechanistic of learning and memory. An array of biochemical and
      histopathological tests were performed to demonstrate the extent of damage
      induced by HFD. RESULTS: HFD-treated rats exhibited marked accentuation in brain
      thiobarbituric acid reactive species, Interleukin-1beta, tumor necrosis factor
      alpha levels, myeloperoxidase and acetylcholinestrase activity in addition to
      attenuation of glutathione levels and superoxide dismutase activity as compared
      to rats fed on normal chow diet. Consistent rise in serum cholesterol level was
      also indicated. Histopathological examination of cerebral cortex using
      hematoxylin and eosin and congo red staining methods demonstrated significant
      neutrophilic incursion and amyloid deposition. Administration of forskolin to HFD
      treated rats improved memory functions, biochemical and histopathological
      alterations. Concomitant administration of ketoconazole, a PXR antagonist with
      forskolin prevented the observed protective effects. CONCLUSION: Our findings
      signify that forskolin defends HFD induced cognitive deficits. Current plethora
      of results also defines the potential of PXR in neuroprotective action of
      forskolin in dementia.

PMID- 29367104
TI  - Farnesoid X receptor antagonist exacerbates dyslipidemia in mice.
AB  - BACKGROUND: The effects of farnesoid X receptor (FXR) antagonists on plasma lipid
      profile in mice have not been investigated thus far. The aim of this study was to
      investigate the antidyslipidemic effects of an FXR antagonist in dyslipidemic
      mice, and to clarify the mechanisms underlying the lipid modulatory effect.
      METHODS: Compound-T0 (1-100 mg/kg) was orally administered to C57BL/6J mice fed a
      Western-type diet or low-density lipoprotein receptor knockout (LDLR-/-) mice fed
      a Western-type diet for a week, and plasma lipid levels were investigated.
      Effects on lipid clearance, hepatic triglyceride secretion after Triton WR-1339
      challenge, and intestinal lipid absorption were investigated after multiple
      dosing. RESULTS: Compound-T0 significantly increased plasma level of non-high
      density lipoprotein cholesterol in both C57BL/6 and LDLR-/- mice; in addition, it
      significantly increased plasma triglyceride level in LDLR-/- mice. Compound-T0
      failed to enhance the clearance of 3,3'-dioctadecylindocarbocyanine (DiI)-labeled
      LDL in C57BL/6J mice. Although compound-T0 did not affect triglyceride clearance
      and hepatic triglyceride secretion, it significantly increased intestinal
      [3H]cholesterol absorption in LDLR-/- mice. CONCLUSIONS: It was found that the
      FXR antagonist, compound-T0 exacerbated dyslipidemia in mice because it enhanced
      intestinal lipid absorption via acceleration of bile acid excretion.

PMID- 29367105
TI  - Advancing methods for health priority setting practice through the contribution
      of systems theory: Lessons from a case study in Ethiopia.
AB  - Setting priorities for health services is a complex and value laden process. Over
      the past twenty years, there has been considerable scholarly attention paid to
      strengthening fairness and legitimacy using the prominent ethical framework,
      Accountability for Reasonableness (A4R). A variety of case studies applying A4R
      have advanced our conceptual understanding of procedural fairness, and have
      highlighted the significance of context through its application. There is a
      paucity of research, however, that rigorously examines how and to what extent
      context influences health priority setting processes and the establishment of
      procedural fairness. We argue here that to study context rigorously requires
      taking a holistic view of the system by examining the dynamics and
      interrelationships within it. Using the Transformative Systems Change Framework
      (TSCF), this investigation sought to examine the influence of system factors on
      priority setting practice and procedural fairness. A qualitative case study of
      Ethiopian district health planning was undertaken in 2010 and 2011. Methods
      included 58 qualitative interviews with decision makers, participant observation,
      and document analysis. Data analysis followed in three phases: i) an inductive
      analysis of district health priority setting to highlight experiences across each
      of the three districts selected, ii) deductive analysis applying A4R and the TSCF
      independently; and iii) a synthesis of concepts of priority setting practice and
      procedural fairness within a broader, theoretical understanding of the system.
      Through the application of the TSCF, a nuanced understanding of priority setting
      practice is revealed that situates this process within a system of interdependent
      components that include: norms, operations, regulations, and resources. This
      paper offers a practical guide attuned to system features influencing the design,
      implementation, and sustainability of greater fairness in health priority setting
      practice.

PMID- 29367106
TI  - LncRNA MIR31HG overexpression serves as poor prognostic biomarker and promotes
      cells proliferation in lung adenocarcinoma.
AB  - MIR31HG, as the host gene of miR-31, has been suggested to involve in various
      cancer developments. However, little is known about the clinical significance and
      biological function of MIR31HG in lung adenocarcinoma. In our study, we found
      MIR31HG was highly expressed in lung adenocarcinoma tissues and cell lines, and
      associated with clinical staging, N classification, M classification and
      differentiated degree. Survival analysis showed MIR31HG high-expression was an
      independent unfavorable prognostic factor for lung adenocarcinoma patients. Loss
      of-function studies suggested down-regulation of MIR31HG inhibited lung
      adenocarcinoma cells proliferation and blocked cell-cycle, but has no effect on
      cell apoptosis. There was no correlation between MIR31HG and miR-31 expression in
      lung adenocarcinoma tissues, down-regulation of MIR31HG had no effect on the
      expression of miR-31 in lung adenocarcinoma cells. In conclusion, MIR31HG high
      expression is an independent unfavorable prognostic factor for lung
      adenocarcinoma patients, and serves an oncogenic role to modulate lung
      adenocarcinoma cells proliferation and cell-cycle.

PMID- 29367107
TI  - Salinomycin derivatives exhibit activity against primary acute lymphoblastic
      leukemia (ALL) cells in vitro.
AB  - Salinomycin (SAL) and monensin (MON) are polyether ionophore antibiotics commonly
      used in veterinary medicine. They are known from their anti-cancer activity
      against various types of cancer cells, including those that display multi-drug
      resistance as well as cancer stem cells. In order to increase the biological
      activity profile and reduce toxicity against normal cells, while retaining the
      activities in the micromolar range, a library of ester and amide derivatives of
      SAL was synthesized and previously reported. In this paper, we examined the
      activity of SAL, its ten derivatives, and MON on primary acute lymphoblastic
      leukemia cells. MON and six SAL derivatives were more potent than SAL in cell
      viability assays. Further, selected active SAL analogs induced characteristics of
      apoptotic cell death and increased expression of p53. Moreover, SAL acted
      synergistically with the Bcl-2 inhibitor ABT-263, whereas 2,2,2-trifluoroethyl
      ester, the most active analog of SAL, antagonized ABT-263, suggesting possible
      differences in molecular mechanism.

PMID- 29367108
TI  - Thymoquinone activates MAPK pathway in hippocampus of streptozotocin-treated rat
      model.
AB  - Streptozotocin (STZ), a glucosamine-nitrosourea compound, produces deficiencies
      in learning, memory, and cognitive functions when it was administered
      intracerebroventricularly (i.c.v). In molecular level, increase in
      neuroinflammation and oxidative stress in brain, and decrease in the number of
      surviving neurons are the outcomes of STZ administration. Herein, we aimed to
      investigate the effect of thymoquinone (TQ), an anti-inflammatory,
      immunomodulatory and neuroprotective agent, on STZ-induced neurodegeneration in
      rats. For this purpose, bilateral i.c.v. injection of STZ (3 mg/kg) was given to
      adult female rats on days 1 and 3. TQ (20 mg/kg/day in cornoil) was administered
      intragastrically to rats for 15 days starting from the 15th day of STZ injection.
      The Morris water maze test and passive avoidance test were applied to measure the
      learning and memory performance of animals. Following the behavioral tests, all
      of the rats were sacrificed for evaluation of molecular alterations. Rats in the
      STZ-TQ group showed higher performance in passive avoidance test than rats in the
      STZ group whose memory performance declined compared to control group. The worse
      memory performance in STZ group was correlated with low number of surviving
      neurons and high number of degenerating neurons. In addition, an increase in APOE
      expression and a decrease in NGF expression were observed with STZ injection.
      Administration of TQ reversed these STZ-triggered cognitive and molecular
      alterations. In the present study, we observed the neuroregenerative effects of
      TQ by activation of JNK protein, upregulation of mir-124, and downregulation of
      ERK1/2 and NOS enzymes. The same ameliorative effect of TQ was also observed in
      the pTau protein expression. To sum up, we can say that the healing effect of TQ
      on STZ induced neurodegeneration opens a new door for the development of
      Alzheimer's disease treatment using natural products as an adjuvant when their
      action mechanism was explained in detail.

PMID- 29367109
TI  - NF-kappaB-induced WIP1 expression promotes colorectal cancer cell proliferation
      through mTOR signaling.
AB  - Colorectal cancer (CRC) is one of the major causes of cancer deaths worldwide.
      Wild-type p53-induced protein 1 (WIP1) is overexpressed in multiple human cancers
      and acted as an oncogene. This study was aimed to investigate the effect of WIP1
      in colorectal cancer growth and analyzed underlying mechanisms. Herein, we
      determined WIP1 expression in CRC tissues and cell lines, as well as evaluated
      its detailed function in CRC cell proliferation. Several factors have been
      reported to mediate WIP1 effects; herein, we examined the involvement of mTOR and
      p21 in WIP1 regulation of CRC cell proliferation. Moreover, NF-kappaB has been
      regarded as a positive transcriptional regulator of WIP1 to activate its
      expression. NF-kappaB knockdown suppressed CRC cell proliferation, which could be
      reversed by WIP1 overexpression, through p21 and mTOR. Further, we examined the
      binding of NF-kappaB to the promoter region of WIP1. In CRC tissues, NF-kappaB
      expression was significantly up-regulated, and positively correlated with WIP1
      expression, suggesting that inhibiting NF-kappaB expression to attenuate its
      activating effect on WIP1 expression presented a promising strategy of
      controlling excess proliferation of CRC cell. In summary, WIP1 promotes CRC
      proliferation through p21 and mTOR, both downstream targets of p53; NF-kappaB
      served as a positive transcriptional regulator of WIP1 to activate its expression
      and affect its function in CRC cells. Our finding provided a novel strategy for
      treatment for CRC.

PMID- 29367110
TI  - Antidotal or protective effects of Curcuma longa (turmeric) and its active
      ingredient, curcumin, against natural and chemical toxicities: A review.
AB  - Curcuma longa is a rhizomatous perennial herb that belongs to the family
      Zingiberaceae, native to South Asia and is commonly known as turmeric. It is used
      as herbal remedy due to the prevalent belief that the plant has medical
      properties. C. longa possesses different effects such as antioxidant, anti-tumor,
      antimicrobial, anti-inflammatory, wound healing, and gastroprotective activities.
      The recent studies have shown that C. longa and curcumin, its important active
      ingredient, have protective effects against toxic agents. In this review article,
      we collected in vitro and animal studies which are related to protective effects
      of turmeric and its active ingredient against natural and chemical toxic agents.

PMID- 29367111
TI  - Zingerone attenuates diabetic nephropathy through inhibition of nicotinamide
      adenine dinucleotide phosphate oxidase 4.
AB  - Diabetes affects a large proportion of population wide across the world and
      kidney is a main target organ of diabetic complications. Zingerone is a stable
      active component derived from dry ginger rhizome. We investigated the effect of
      zingerone on diabetic nephropathy and explored the possible mechanisms. We showed
      that zingerone decreased the levels of serum insulin, C-peptide and glycosylated
      hemoglobin A1c. The levels of blood urea nitrogen (BUN), serum creatinine,
      urinary albumin content and albumin/creatinine ratio (ACR) were reduced by
      zingerone. Moreover, zingerone attenuated the pathological injuries of kidneys,
      reduced the surface area of Bowman's capsule, Bowman's space, glomerular tuft,
      and decreased the expression of collagen IV and fibronectin in kidneys in db/db
      mice. The high levels of triglyceride and cholesterol, and high expression of
      TNFalpha and IL-6 were decreased by zingerone. Furthermore, zingerone decreased
      the level of MDA and increased the content of glutathione (GSH). NADPH oxidase 4
      (NOX4) expression was significantly increased in kidneys of db/db mice and in HK
      2 cells after exposure to high glucose. Zingerone significantly decreased the
      expression of NOX4 in vivo and in vitro. Upregualtion of NOX4 significantly
      inhibited zingerone-induced protective effects against the cytotoxicity of high
      glucose. Downregulation of NOX4 was responsible for zingerone-exhibited
      pharmacological activities and reduction of diabetic nephropathy. Overall,
      zingerone is a promising therapeutic treatment to attenuate diabetic nephropathy.

PMID- 29367112
TI  - Osteogenic protein-1 attenuates the inflammatory cytokine-induced NP cell
      senescence through regulating the ROS/NF-kappaB pathway.
AB  - BACKGROUND: Nucleus pulposus (NP) cell senescence correlates with disc
      degeneration. Previous studies imply that inflammation induces NP cell
      senescence. Osteogenic protein-1 (OP-1) is helpful for regenerating degenerative
      disc. OBJECTIVE: To investigate whether OP-1 treatment can protect against the
      inflammatory cytokine TNF-alpha-induced NP cell senescence, and its potential
      mechanism. METHODS: Rat NP cells were cultured in either basic culture medium or
      basic culture medium with the inflammatory cytokine TNF-alpha for 3 days. OP-1
      was added into the culture medium of TNF-alpha-treated NP cells to investigate
      the protective effects of OP-1 against cellular senescence. NP cell senescence
      was evaluated by some direct and indirect parameters, such as senescence
      associated beta-galactosidase (SA-beta-Gal) activity, cell cycle, telomerase
      activity, expression of senescence markers (p16 and p53), and the matrix
      homeostatic phenotype. Additionally, intracellular reactive oxygen species (ROS)
      and the activity of the NF-kappaB pathway were also analyzed. RESULTS: Compared
      with the control group, the inflammatory cytokine TNF-alpha significantly
      promoted NP cell senescence, reflected by the increase in SA-beta-Gal activity,
      G0/G1 phase fraction and senescence markers (p16 and p53) expression, and the
      decrease in telomerase activity and matrix macromolecules (aggrecan and collagen
      II) expression. However, OP-1 suppressed the effects of TNF-alpha on NP cell
      senescence. Further analysis showed that OP-1 reduced ROS generation in TNF-alpha
      treated NP cells, as well as the resulting activity of the NF-kappaB pathway.
      CONCLUSION: OP-1 can attenuate inflammatory cytokine TNF-alpha-induced NP cell
      senescence, and the ROS/ NF-kappaB pathway may participate in this regulatory
      process. This study provides that OP-1 may be efficacy in retarding inflammation
      exacerbated disc degeneration.

PMID- 29367113
TI  - Distribution and transfer of potentially toxic metal(loid)s in Juncus effusus
      from the indigenous zinc smelting area, northwest region of Guizhou Province,
      China.
AB  - We collected samples (i.e., the aerial parts and roots of Juncus effusus and
      their growth media) in the indigenous zinc smelting area in the northwest region
      of Guizhou Province, China, and we measured and analyzed potentially toxic
      metal(loid)s (arsenic, As; cadmium, Cd; chromium, Cr; copper, Cu; mercury, Hg;
      lead, Pb and zinc, Zn) in these samples. The results include the following:
      First, there is a high concentration of one or more potentially toxic
      metal(loid)s in the slag and surrounding soil in the research area. This
      situation might be caused by metal(loid) damage or contamination due to the
      circumstances. Additionally, Juncus effusus in the indigenous zinc smelting area
      are contaminated by some potentially toxic metal(loid)s; since they are used for
      Chinese medical materials, it is especially significant that their As, Cd and Pb
      concentrations are greater than their limited standard values. Finally, both the
      bioconcentration factors and transfer factors for most potentially toxic
      metal(loid)s in Juncus effusus are less than 1 in the study area. Therefore, we
      suggest that Juncus effusus could be used for phytostabilization or as a pioneer
      plant for phytoremediation of potentially toxic metal(loid)s because it has a
      tolerance and exclusion mechanism for these metal(loid)s in the research
      district.

PMID- 29367114
TI  - A gentle reminder about p-values: What are we actually teaching?

PMID- 29367115
TI  - Alcohol-induced blackouts, subjective intoxication, and motivation to decrease
      drinking: Prospective examination of the transition out of college.
AB  - OBJECTIVE: We prospectively examined whether subjective intoxication serves as a
      risk factor for experiencing alcohol-induced blackouts. We then examined whether
      subjective intoxication and/or blackouts predicted motivation to decrease their
      drinking, and whether this motivation to change would promote future changes in
      drinking behavior. METHOD: Participants (N=1854, 62.1% female, 53.2% Caucasian,
      Mage=21.8) were recruited the summer prior to matriculating into a large, public
      university to complete a 6-year longitudinal study. Self-reported motivation to
      decrease their drinking behavior, their frequency of blackouts, quantity of
      alcohol consumption, and subjective intoxication (i.e., feeling drunk) were
      assessed annually during the transition out of college (Years 4-6). RESULTS: In a
      cross-lagged model, subjective intoxication (i.e., feeling drunk) prospectively
      predicted experiencing blackouts (p<0.001). Controlling for both objective (e.g.,
      quantity) and subjective intoxication, blackouts at Year 4 predicted greater
      motivation to decrease drinking behavior at Year 5 (p<0.01), but this motivation
      did not predict less quantity of alcohol use by Year 6 (p=0.076). CONCLUSIONS:
      Subjective intoxication is a robust predictor of blackouts across time.
      Additionally, blackouts are modest, developmentally-limited predictors of
      motivation to change drinking behavior, but blackouts do not predict future
      behavior change.

PMID- 29367116
TI  - Contingency management for college student smokers: The role of drinking as a
      moderator and mediator of smoking abstinence during treatment.
AB  - INTRODUCTION: Contingency management (CM) is effective for promoting smoking
      abstinence; however, moderators and mediators of CM treatment efficacy in young
      adult populations are under-explored. We leveraged fine-grained data from a large
      randomized controlled trial: 1) to determine whether early attainment of
      sustained abstinence mediated the effect of treatment on abstinence; 2) to test
      whether heavy drinking moderated the effect of treatment on abstinence; and 3) to
      test a serial mediation model of the effects of drinking during early treatment
      on sustained smoking abstinence. METHODS: College student smokers (N=110) were
      randomized to receive either CM treatment or noncontingent reinforcement (NR)
      over a 21-day treatment period. All participants received $5 for providing twice
      daily breath carbon monoxide (CO) samples. In CM, additional money was provided
      for samples that indicated smoking reduction (Initial Phase; first 7days), and
      for samples <=5ppm (Abstinence Phase; following 14days). RESULTS: CM treatment
      led to greater sustained abstinence relative to NR. Longer sustained abstinence
      in the Initial Phase partially mediated the effect of treatment on sustained
      abstinence in the Abstinence Phase. Heavier pretreatment drinkers had shorter
      periods of sustained abstinence in the Abstinence Phase; this effect was greater
      in CM. A serial mediation model determined that increased drinking during the
      Initial Phase led to decreased sustained abstinence, which then led to decreased
      sustained abstinence in the Abstinence Phase. CONCLUSIONS: These data provide a
      greater understanding of how heavy drinking and early sustained abstinence may
      affect success during treatment in young adults undergoing contingency management
      treatment for smoking.

PMID- 29367117
TI  - Feasibility of addition of polyphenol-rich vegetable extracts in whole cooked
      products: Benefits and drawbacks.
AB  - Pork loins were cooked with 5 different polyphenol-rich vegetable extracts:
      Polygonum cuspidatum, oregano extract, rosemary extract, white grape extract and
      green tea extract. These extracts were added to brine, taking into account their
      solubility, for subsequent injection and cooking. Loins with added vegetable
      extracts exhibited higher antioxidant effect compared to controls, as shown by
      the oxidized/reduced ascorbate ratio, the potential of reduction and the fat
      oxidation rate. However, some effects were observed in terms of taste, colour
      changes and, in some cases (green tea and oregano), presence of blots on meat
      slices. Poor diffusion of the brine through the muscle fibres and insolubility of
      the extracts in localized spots are weaknesses of these products. A significant
      amount of polyphenols was lost or destroyed during the cooking phase of the
      process. Sensory tests show that only Polygonum cuspidatum and rosemary extract
      result in an acceptable product. In this case the contribution of active
      molecules in the final product is rather limited.

PMID- 29367118
TI  - Identification of ground meat species using near-infrared spectroscopy and class
      modeling techniques - Aspects of optimization and validation using a one-class
      classification model.
AB  - Chemometric methods permit the construction of classifiers that effectively
      assist in monitoring safety, quality and authenticity of meat based on the near
      infrared (NIR) spectral fingerprints. Discriminant techniques are often
      considered in multivariate quality control. However, when the authenticity of
      meat products is the primary concern, they often lead to an incorrect recognition
      of new samples. The performances of two class modeling techniques (CMT) in order
      to recognize meat sample species based on their NIR spectra was compared - a one
      class classifier variant of the partial least squares method (OCPLS) and the soft
      independent modeling of class analogy (SIMCA). Based on obtained sensitivity and
      specificity values, OCPLS and SIMCA can be considered as an effective CMT for the
      classification of complex natural samples such as studied meat samples (with a
      relatively large variability). Moreover, particular attention was paid to the
      optimization and validation of a one-class classification model.

PMID- 29367119
TI  - Nutritional value and potential chemical food safety hazards of selected Polish
      sausages as influenced by their traditionality.
AB  - Traditional food products have been regaining consumer interest worldwide. The
      aim of the study was to investigate the differences in nutritional value of
      traditional and conventional Polish sausages and to determine potential chemical
      hazards connected with these products. The research material consisted of 5
      varieties of registered traditional sausages and 4 varieties of conventional
      sausages. The nutritional value was identified based on selected indicators:
      protein, fat, NaCl, total ash, water, Feder's number, Ca, Fe, Mg, K, Zn, Cr, Cu;
      whereas the chemical food safety - based on: nitrates and nitrites, total and
      added phosphorus, Cd, Pb. The results of this study show that traditional
      sausages have higher content of protein, zinc, magnesium and potassium as well as
      lower concentrations of calcium, water and total ash, plus lower water to protein
      ratio in comparison to conventional counterparts. Polyphosphates are not used in
      the production of traditional sausages and the amounts of added nitrites are at
      low levels.

PMID- 29367120
TI  - Optimum hexametaphosphate concentration to inhibit efflorescence formation in dry
      fermented sausages.
AB  - The occurrence of efflorescences on the surface of dry fermented sausages
      represents a current issue for the meat processing industry. Preventing the
      efflorescence formation by the addition of sodium hexametaphosphate (SHMP) was
      shown to be promising in a previous study. The optimum SHMP addition was studied
      by adding SHMP (0.0, 1.0, 3.0, and 5.0g/kg) directly to the sausage batter.
      Visual and chemical analyses were conducted during 8weeks of storage under
      modified atmosphere. Visual analyses revealed significant lower amounts of
      efflorescences on the sausage surface after 8weeks when 1.0 (27.1%), 3.0 (9.0%),
      and 5.0g/kg SHMP (3.4%) were added, compared to the control with 38.0%
      efflorescences. SHMP significantly affected the occurrence (8weeks) of magnesium
      on the surface: +85.5%, +23.7%, +3.5%, and -28.2% for 0.0, 1.0, 3.0, and 5.0g/kg,
      respectively. The addition of 4.785g/kg was calculated to fully inhibit the
      formation of efflorescences by complexing magnesium ions.

PMID- 29367121
TI  - Effect of ultraviolet light, organic acids, and bacteriophage on Salmonella
      populations in ground beef.
AB  - This study investigated individual and combined effects of organic acids,
      bacteriophages, and ultraviolet light interventions on Salmonella populations in
      ground beef. Beef trim was inoculated with four Salmonella strains to result in a
      contamination level of 3.5 log CFU/g after grinding. Lactic (LA) and peroxyacetic
      (PAA) acids, bacteriophages (S16 and FO1a) (BA), and ultraviolet light (UV) were
      applied on fresh trim prior to grinding. Applications of individual or combined
      organic acids did not significantly decrease Salmonella populations in ground
      beef. Individual applications of BA and UV light decreased approximately 1 log
      CFU/g (P<0.05). Combined applications of BA and UV provided an optimal decrease
      of 2 log CFU/g (P<0.05). Organic acid applications do not reduce Salmonella
      populations in ground beef when applied on trim prior to grinding. Combined
      applications of UV and BA may be used in industry settings to improve Salmonella
      control in ground beef.

PMID- 29367122
TI  - Clinical classification criteria for nonspecific low back pain: A Delphi-survey
      of clinical experts.
AB  - BACKGROUND: Nonspecific low back pain (NSLBP) is a common problem. Attempts have
      been made to classify NSLBP patients into homogenous subgroups. Classification
      systems based on identifying the underlying mechanism(s) driving the disorder are
      clinically useful to guide specific interventions. OBJECTIVE: To establish
      consensus among experts regarding clinical criteria suggestive of a dominance of
      'articular', 'myofascial', 'neural', 'central', and 'sensorimotor control'
      dysfunction patterns (DPs) in NSLBP patients. STUDY DESIGN: A 2-phase sequential
      design of a focus group and Delphi-study. METHODS: A focus group with 10 academic
      experts was organized to elaborate on the different DPs discernible in LBP
      patients. Consecutively, a 3-round online Delphi-survey was designed to obtain
      consensual symptoms and physical examination findings for the 5 DPs resulting
      from the focus group. RESULTS: Fifteen musculoskeletal physical therapists from
      Belgium and the Netherlands experienced in assessing and treating LBP patients
      completed the Delphi-survey. Respectively, 34 (response rate, 100.0%), 20 (58.8%)
      and 15 (44.12%) respondents replied to rounds 1, 2 and 3. Twenty-two 'articular',
      20 'myofascial', 21 'neural', 18 'central' and 11 'sensorimotor control' criteria
      reached a predefined >=80% consensus level. For example, after round 2, 85.0% of
      the Delphi-experts agreed to identify 'referred pain below the knee' as a
      subjective examination criterion suggestive for a predominant 'neural DP'.
      CONCLUSION: These indicators suggestive of a clinical dominance of the proposed
      DPs could help clinicians to assess and diagnose NSLBP patients. Future
      reliability and validity testing is needed to determine how these criteria may
      help to improve physical therapy outcome for NSLBP patients.

PMID- 29367123
TI  - Covariance data evaluation for 233U.
AB  - The FITWR program was developed and applied to experimental nuclear data by using
      the weighted least square method with nonlinear regression for high-order
      polynomials to meet the growing demands of nuclear data. It can deal with
      provided variance and covariance data along with experimental data to obtain
      evaluation data. The aim of this study was to investigate the validity and
      accuracy of the cross-sectional data for 233U to perform the calculations of the
      critical system by performing the pre-calculations using the SAMMY code as
      follows. First, by using the Bayes method, which is available in the SAMMY code,
      and then by using the FITWR code, which consists of facilitated weighted least
      square method with nonlinear regression. To validate the FITWR fitting method, a
      comparison was made with the Bayes method for several benchmarks, and it was
      tested in both thermal and fast-energy regions. All the computational work done
      for this paper was carried out at IMAN1 Center - Jordan's National Supercomputing
      Center.

PMID- 29367124
TI  - Application of the 'Spiking' method to the measurement of low dose radiation (<=
      1Gy) using alanine dosimeters.
AB  - Alanine dosimeters are limited in radiotherapy by poor sensitivity at low doses
      (< 5Gy). A set of alanine dosimeters were 'spiked' with a large dose of
      radiation, (~30Gy, 6MV X-rays) and additional doses ranging between 0.5 and 10Gy.
      The radical yield was measured by Electron Paramagnetic Resonance (EPR)
      spectroscopy, and after subtraction of the contribution from the "spike" dose, a
      linear correlation between the radiation dose and the area of the central EPR
      signal was obtained for doses between 0.5 and 10Gy (regression value of 0.9890),
      and for the central peak's amplitude (regression value of 0.9895). Overall, this
      method is easy to perform, requires no complex EPR signal analysis, and offers
      much potential to extend the current usage of alanine dosimeters in radiotherapy.

PMID- 29367125
TI  - Graph cuts and neural networks for segmentation and porosity quantification in
      Synchrotron Radiation X-ray MUCT of an igneous rock sample.
AB  - X-ray Synchrotron Radiation Micro-Computed Tomography (SR-uCT) allows a better
      visualization in three dimensions with a higher spatial resolution, contributing
      for the discovery of aspects that could not be observable through conventional
      radiography. The automatic segmentation of SR-uCT scans is highly valuable due to
      its innumerous applications in geological sciences, especially for morphology,
      typology, and characterization of rocks. For a great number of uCT scan slices, a
      manual process of segmentation would be impractical, either for the time expended
      and for the accuracy of results. Aiming the automatic segmentation of SR-uCT
      geological sample images, we applied and compared Energy Minimization via Graph
      Cuts (GC) algorithms and Artificial Neural Networks (ANNs), as well as the well
      known K-means and Fuzzy C-Means algorithms. The Dice Similarity Coefficient
      (DSC), Sensitivity and Precision were the metrics used for comparison. Kruskal
      Wallis and Dunn's tests were applied and the best methods were the GC algorithms
      and ANNs (with Levenberg-Marquardt and Bayesian Regularization). For those
      algorithms, an approximate Dice Similarity Coefficient of 95% was achieved. Our
      results confirm the possibility of usage of those algorithms for segmentation and
      posterior quantification of porosity of an igneous rock sample SR-uCT scan.

PMID- 29367126
TI  - Remote clinical decision making: Evaluation of a new education module.

PMID- 29367127
TI  - Biomass based hydrogen production by dark fermentation-recent trends and
      opportunities for greener processes.
AB  - The generation of biohydrogen as source of biofuel/bioenergy from the wide
      variety of biomass has gathered a substantial quantum of research efforts in
      several aspects. One of the major thrusts in this field has been the pursuit of
      technically sound and effective methods and/or approaches towards significant
      improvement in the bioconversion efficiency and enhanced biohydrogen yields. In
      this perspective, the present contribution showcases the views formulated based
      on the latest advances reported in dark fermentative biohydrogen production
      (DHFP), which is considered as the most feasible route for commercialization of
      biohydrogen. The potential prospects and future research avenues are also
      presented.

PMID- 29367128
TI  - Remediation of As(III) and Cd(II) co-contamination and its mechanism in aqueous
      systems by a novel calcium-based magnetic biochar.
AB  - A novel calcium-based magnetic biochar (Ca-MBC), made by pyrolyzing the mixture
      of rice straw, iron oxide (Fe3O4) and calcium carbonate (CaCO3), was developed in
      this study for remediation of co-pollution of arsenic and cadmium.
      Characteristics of the material showed that Fe3O4 and CaCO3 were adhered on the
      surface of biochar. The experiments on the effects of pH, adsorption kinetics and
      isotherm revealed that the Ca-MBC had a great ability to adsorb arsenic and
      cadmium within 0.5 h for cadmium and 12 h for arsenic with a maximum adsorption
      capacity of 6.34 and 10.07 mg g-1, respectively, and that the adsorption of both
      metals was pH-dependent from 2 to 12 with an optimal pH of pH 5. The mechanism of
      co-adsorption of Cd(II) and As(III) included both competitive and synergistic
      effects. The presence of As(III) enhanced Cd(II) adsorption by 3-16% while Cd(II)
      addition suppressed As(III) adsorption by 15-33%. The synergistic effects on
      As(III) and Cd(II) adsorption had resulted from the electrostatic interaction and
      the formation of type B ternary surface complexes. These new insights provide
      valuable information for the application of Ca-MBC as a potential adsorbent in
      treatment of water contaminated with As(III) and Cd(II).

PMID- 29367129
TI  - Rapid and selective recovery of acetophenone from petrochemical effluents by
      crosslinked starch polymer.
AB  - A porous crosslinked starch polymer (CSTO) using bitolylene diisocyanate as
      crosslinker was prepared by a facile method and used to selectively recover
      acetophenone (AP) from petrochemical effluent mainly containing AP and 1
      phenylethanol (PE). The theoretical calculation results indicated that AP
      exhibited the superior affinity toward the adsorption sites of CSTO through
      noncovalent interactions. The adsorption measurements showed that, due to the
      large surface area and high affinity of phenyl rings, CSTO displayed an extremely
      rapid adsorption rate, a desirable adsorption capacity and selectivity to AP. The
      adsorption kinetics and isotherms in single solute system agreed well with the
      pseudo-second-order kinetic model and Freundlich isotherm model, and the
      adsorption was exothermic and spontaneous. Furthermore, CSTO showed excellent
      reusability for selective adsorption of AP from equimolar mixture of AP/PE,
      prompting us to further examine its applicability. In the practical application,
      CSTO also revealed a fast, preferential and reusable adsorption of AP from actual
      petrochemical effluent.

PMID- 29367130
TI  - Surface molecular imprinting on carbon microspheres for fast and selective
      adsorption of perfluorooctane sulfonate.
AB  - Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant with high
      biological and chemical stability. It is important to develop fast and selective
      adsorption method for PFOS wastewater treatment. In this study, novel molecularly
      imprinted polymer (MIP) for PFOS adsorption was prepared. To obtain rapid
      adsorption kinetics, the MIP has been designed as the surface polymer using the
      carbon microsphere as carrier (MIP-CMSs). To ensure high adsorption selectivity
      to the template, two monomers with different functional structures, namely
      methacryloyloxyethyl trimethyl ammonium chloride (DMC) and 2
      (trifluoromethyl)acrylic acid (TFMA), were employed as bi-functional monomers.
      The structure and morphology of MIP-CMSs were characterized using field emission
      scanning electron microscopy with the energy dispersive spectrometer,
      transmission electron microscopy, and Fourier transformation infrared
      spectroscopy. Based on the adsorption experiments, it was concluded that MIP-CMSs
      had specific binding property for PFOS on acidic condition. The adsorption
      equilibrium time was 1h, while the adsorption capacity was 75.99 mg g-1 at pH 3.
      Coexistence with contaminants with different structures had little influence on
      the selectivity for PFOS. The spent MIP-CMSs could be regenerated by the methanol
      and acetic acid mixed solution. The electrostatic interaction and molecular size
      played important roles in recognizing the target compound in the adsorption
      process.

PMID- 29367131
TI  - Stereochemistry of ephedrine and its environmental significance: Exposure and
      effects directed approach.
AB  - Analysis of drugs and pharmaceuticals in the environment is typically performed
      with non-chiral chromatographic techniques. The environmental risks posed by
      chiral compounds analysed in this way must therefore be assumed to be independent
      of chirality, meaning that each enantiomer is equally potent in toxicity and long
      lived in stability. This manuscript examines the degradation of each of the four
      isomers of ephedrine in river simulating microcosms and links this to toxicity
      data obtained by exposing three different organisms (D. magna, P. subcapitata and
      T. thermophila) to each of the isomers individually. Microcosms showed that
      significant degradation only occurred in biotic conditions and that only two
      isomers (1R,2S-(-)-ephedrine, 1S,2S-(+)-pseudoephedrine) degraded significantly
      over a period of fourteen days. This is concerning because at least one of the
      non-degraded isomers (1S,2R-(+)-ephedrine) has been observed in wastewater
      effluent, which discharges directly into rivers, meaning these isomers could be
      persistent in the environment. We also observed formation of 1S,2R-(+)-ephedrine
      in single isomer 1R,2S-(-)-ephedrine river simulating microcosms. Human liver
      microsome assays and mass spectrometry based data mining revealed that 1S,2R-(+)
      ephedrine is not human derived but it could be formed as a results of microbial
      metabolic processes. Across all three organisms tested the persistent isomers
      (1S,2R-(+)-ephedrine and 1R,2R-(-)-pseudoephedrine) were more toxic than those
      that undergo degradation; meaning that if these isomers are entering or formed in
      the environment they might represent a potentially hazardous contaminant.

PMID- 29367132
TI  - Synthesis of zincphthalocyanine-based conjugated microporous polymers with rigid
      linker as novel and green heterogeneous photocatalysts.
AB  - The novel zincphthalocyanine-based conjugated microporous polymers with rigid
      linker (alpha-ZnPc-CMP and beta-ZnPc-CMP) were synthesized by copolymerization of
      zinc phthalocyanine (ZnPc) and 4, 6-diaminoresorcinol dihydrochloride (DADHC).
      The alpha-ZnPc-CMP and beta-ZnPc-CMP were utilized as heterogeneous
      photocatalysts to degrade Rhodamine B (RhB) in aqueous solution. It is the first
      time for MPc-based CMPs used as heterogeneous photocatalysts for photodegradation
      of RhB to date. The highly ordered skeletal alignment and two-dimensional open
      channel structure of alpha-ZnPc-CMP and beta-ZnPc-CMP not only solve the
      aggregation of ZnPc and enhance its photocatalytic activity, but also facilitate
      the recycling and avoid the secondary pollution. The chemical structures and
      morphologies of alpha-ZnPc-CMP and beta-ZnPc-CMP were well characterized by
      Fourier transform infrared spectra (FT-IR), solid-state 13C nuclear magnetic
      resonance (13C NMR), scanning electron microscopy (SEM), N2-sorption/ desorption
      and X-ray diffraction (XRD). The solubility experiments and thermogravimetric
      analysis (TGA) showed they have good chemical stability and recyclability.
      Furthermore, the photocatalytic tests indicated alpha-ZnPc-CMP and beta-ZnPc-CMP
      have excellent photocatalytic performances for degradation of RhB (3 h, degraded
      98 and 97.47%) in the presence of H2O2 under visible-light irradiation. All
      results reveal that alpha-ZnPc-CMP and beta-ZnPc-CMP have great potential as
      photocatalysts on the degradation of organic dye contaminants. Moreover, the
      possible reaction mechanism of alpha-ZnPc-CMP and beta-ZnPc-CMP as photocatalysts
      for the degradation of RhB is proposed.

PMID- 29367133
TI  - Occurrence and fate of colloids and colloid-associated metals in a mining
      impacted agricultural soil upon prolonged flooding.
AB  - Colloids formed during soil flooding can potentially facilitate the mobilization
      of metal contaminants. Here, laboratory batch incubations with a contaminated
      soil were performed to monitor temporal changes in the porewater dynamics of
      metals, the morphology and composition of colloids, and the speciation of
      colloids-associated metals during 30 days of flooding. The concentrations of
      colloidal and dissolved metals increased initially and peaked at a certain time,
      but then decreased with the on-going sulfate reduction. The combined analysis of
      spectrometric, spectroscopic, and size-fractionation results revealed that the
      dynamics of Cu were dominated by microbe-associated colloids and were mediated
      largely by Cu(0) biomineralization and subsequent sulfidation, while the microbe
      associated and freely dispersed colloids were equally relevant for governing the
      dynamics of Cd and Pb. Mobilization of Zn, on the other hand, was dominated by
      its dissolved form, probably due to the low thermodynamic stability of Zn
      sulfide. Additionally, adsorption via organic functional groups was another
      mechanism for metal incorporation into colloids. We also provided direct
      spectroscopic evidence for the formation and persistence of dispersed
      heterocolloids consisting of CuxS and CdS during flooding. Our findings suggest
      that colloids-induced metal mobilization should be considered in assessing
      bioavailability and risks of metals in contaminated soils upon flooding.

PMID- 29367134
TI  - Impact of TiO2 on the chemical and biological transformation of formulated chiral
      metalaxyl in agricultural soils.
AB  - The impacts of TiO2 on the chemical and biological transformation of racemic
      metalaxyl wettable powder (rac-metalaxyl WP) in agricultural soils, and soil
      microorganisms were investigated. Under simulated solar irradiation, TiO2 highly
      promoted the transformation of rac-metalaxyl WP without changing the enantiomer
      fraction, with the promotion amplitude (60-1280%) being dependent on TiO2
      characteristics. TiO2 characteristics showed different influence on the
      transformation of rac-metalaxyl WP in soils and aqueous solutions because their
      characteristics changed differently in soils. The impact of the mancozeb and
      other co-constituents on the transformation of rac-metalaxyl WP was smaller in
      soil media than in aqueous solution. Autoclave sterilization changed soil
      properties and subsequently weakened the promotion effects of TiO2 on the
      chemical transformations of rac-metalaxyl WP to 0-233%. Microorganism biomass and
      bacterial community were not statistically significant changed by TiO2 exposure
      regardless of rac-metalaxyl WP, suggesting that the promotional effects occurred
      mainly through chemical processes. The results also showed TiO2-soil interactions
      may be strengthened with TiO2 (Degussa P25) aging time in soils, which decreased
      its promotion amplitude from 1060% (without aging) to 880% (aging for 20 days).
      Intermediate formed in soil biological transformation process was different from
      that in TiO2 photocatalysis process.

PMID- 29367135
TI  - Multimedia fate modeling and risk assessment of antibiotics in a water-scarce
      megacity.
AB  - As a result of the widespread use of antibiotics, a large amount of excretion
      from human and animals containing antibiotic residues was discharged into the
      environment with wastewaters and manures, leading to potential adverse effects on
      ecosystem health. To understand the environmental fate of antibiotics, a dynamic
      level IV fugacity model was established here by introducing the novel process of
      nondiffusive wastewater irrigation from water to soil, and applied to a large
      scale water-scarce region, the megacity Beijing. Furthermore, a Monte-Carlo based
      risk assessment approach was employed to evaluate the potential risks posed by
      antibiotics in water, sediment and soil, combined with the soil-water equilibrium
      partitioning method. Model validation, sensitivity and uncertainty analysis
      suggests that the fugacity model can successfully simulate the reported
      concentration data within an average difference of 0.2 logarithmic units. Results
      showed that more than one hundred tonnes of antibiotics were estimated to be
      discharged into the environment of Beijing in 2013, and, resulted in high
      antibiotics levels and posed high potential risks on the aquatic environment. On
      the other hand, although wastewater irrigation increased the antibiotics
      concentrations in soil and even dominated the total transfer fluxes, the overall
      risk levels of antibiotics in the soil were acceptable.

PMID- 29367136
TI  - N- and O- ligand doped mesoporous silica-chitosan hybrid beads for the efficient,
      sustainable and selective recovery of rare earth elements (REE) from acid mine
      drainage (AMD): Understanding the significance of physical modification and
      conditioning of the polymer.
AB  - Silica-chitosan hybrid beads were synthesized via three different methods to
      investigate the selective recovery of REE from AMD. The influence of amino/non
      amino silanes, high molecular weight/high viscous chitosan and N-/O- based
      ligands were studied and their effects on REE removal efficiencies were analyzed.
      The adsorption efficiencies of three various groups of modified beads were
      inspected with respect to feed pH, in a single and a multi-component system, and
      their affinities towards the light and heavy rare earth elements (LREE/ HREEs)
      were interpreted to understand the intra-series REE separation behavior. The
      focus of the study was mainly directed towards utilizing these fabricated beads
      for the recovery of valuable REEs from the real AMD obtained at three different
      sampling depths which was found rich in iron, sulfur and aluminum. Moreover, the
      selectivity of the beads towards REEs improved with silanized and ligand
      immobilized gels and their impacts on REE recovery in the presence of competing
      ions were successfully presented in this paper. Also, the synthesized beads
      showed rapid REE adsorption and recovery within a process time of 5 min. Group II
      adsorbents, synthesized by forming silica-chitosan hybrid beads followed by
      PAN/acac modifications, showed superiority over the other groups of adsorbents.

PMID- 29367137
TI  - Graphene oxide-facilitated transport of levofloxacin and ciprofloxacin in
      saturated and unsaturated porous media.
AB  - In this work, effects of graphene oxide (GO) on the co-transport of the two
      typical Fluoroquinolones (FQs) - levofloxacin (LEV) and ciprofloxacin (CIP) in
      saturated and unsaturated quartz sand media were studied. The adsorption
      isotherms showed that GO had much larger sorption capacities to LEV and CIP than
      sand with the largest Langmuir adsorption capacity of 409 mg g-1 (CIP-GO); while
      the sorption affinity of the two FQs onto the two adsorbents might follow the
      order of CIP-sand > LEV-sand > LEV-GO > CIP-GO. GO promoted the mobility of the
      two FQs in both saturated and unsaturated porous media due to its strong mobility
      and sorption capacity. The GO-bound LEV/CIP was responsible for the LEV/CIP
      transport in the porous media, and transport of GO-bound FQs increased with the
      increasing of initial GO concentration. Under unsaturated conditions, moisture
      showed little effect on the transport of GO-bound CIP; however, the mobility of
      GO-bound LEV reduced with the decreasing of moisture content, suggesting the
      transport of adsorbed LEV from GO to air-water interface. GO sorption reduced the
      antibacterial ability of the two FQs, but they were still effective in inhibiting
      E. coli growth.

PMID- 29367138
TI  - Evaluation of the effectiveness and mechanisms of acetaminophen and methylene
      blue dye adsorption on activated biochar derived from municipal solid wastes.
AB  - The adsorption potential and governing mechanisms of emerging contaminants, i.e.
      acetaminophen or acetyl-para-aminophenol (APAP) and methylene blue (MB) dye, on
      activated carbon derived from municipal solid waste were investigated in this
      work. Results showed that MB adsorption was significantly more effective, with a
      maximum removal of 99.9%, than APAP adsorption (%Rmax = 63.7%). MB adsorption was
      found to be unaffected by pH change, while the adsorption capacity of APAP
      drastically dropped by about 89% when the pH was adjusted from pH 2 to 12.
      Surface reactions during APAP adsorption was dominated by both physical and
      chemical interactions, with the kinetic data showing good fit in both pseudo
      first order (R2 = 0.986-0.997) and pseudo-second order (R2>0.998) models. On the
      other hand, MB adsorption was best described by the pseudo-second order model,
      with R2>0.981, denoting that chemisorption controlled the process. Electrostatic
      attractions and chemical reactions with oxygenated surface functional groups
      (i.e., -OH and -COOH) govern the adsorption of APAP and MB on the activated
      biochar. Thermodynamic study showed that APAP and MB adsorption were endothermic
      with positive DeltaH degrees  values of 16.5 and 74.7 kJ mol-1, respectively.
      Negative DeltaG degrees  values obtained for APAP (-3.7 to -5.1 kJ mol-1) and MB
      (-11.4 to -17.1 kJ mol-1) implied that the adsorption onto the activated biochar
      was spontaneous and feasible. Overall, the study demonstrates the effectiveness
      of activated biochar from municipal solid wastes as alternative adsorbent for the
      removal of acetaminophen and methylene blue dye from contaminated waters.

PMID- 29367139
TI  - An assessment of the performance of municipal constructed wetlands in Ireland.
AB  - While performance assessments of constructed wetlands sites around the world have
      appraised their capacity for effective removal of organics, a large variance
      remains in these sites' reported ability to retain nutrients, which appears to
      depend on differences in design, operation and climate factors. Nutrient
      retention is a very important objective for constructed wetlands, to avoid
      eutrophication of aquatic environments receiving their effluents. This study
      assessed the performance of constructed wetlands in terms of nutrient retention
      and associated parameters under the humid conditions of Ireland's temperate
      maritime climate. A review of the performance of 52 constructed wetland sites
      from 17 local authorities aimed to identify the best performing types of
      constructed wetlands and the treatment factors determining successful compliance
      with environmental standards. Data analysis compared effluent results from
      constructed wetlands with secondary free surface flow or tertiary horizontal
      subsurface flow, hybrid systems and integrated constructed wetlands with those
      from small-scale mechanical wastewater treatment plants of the same size class.
      Nutrient concentrations in effluents of constructed wetlands were negatively
      correlated (p < .01) with specific area, i.e. the ratio of surface area and
      population equivalents. The latest generation of integrated constructed wetlands,
      which had applied design guidelines issued by the Department of the Environment,
      performed best. Storm management design features improved treatment performance
      of constructed wetlands significantly (p < .05) for total suspended solids
      concentrations and exceedance frequency of limit values for total nitrogen.
      Mechanical wastewater treatment plants, secondary free surface water and tertiary
      horizontal subsurface flow wetlands showed a very large variance in effluent
      concentrations for organic and nutrient parameters. E. coli numbers in effluents
      were lowest for integrated constructed wetlands with an arithmetic mean of 89
      MPN/100 ml. Despite Ireland's humid climate, some constructed wetland sites
      achieved long or frequent periods of zero effluent discharge and thus did not
      transfer any waterborne pollution to their receptors during these periods.

PMID- 29367140
TI  - Cost and performance tradeoffs between mail and internet survey modes in a
      nonmarket valuation study.
AB  - Using the results of a choice modeling survey, internet, mail-only and mixed
      internet and mail survey modes were examined with regards to their cost
      effectiveness, representativeness, and willingness to pay (WTP). The topical
      focus of the study was biomass energy generation preferences of the residents of
      Montana, Colorado and Arizona, USA. Compared to the mail and mixed mode samples,
      the internet-only mode produced a sample of respondents that was younger, more
      likely to have a college degree, and more likely to have a household income of at
      least $100,000 per year. However, observed differences in the characteristics of
      the collected sample did not result in significant differences in estimates of
      WTP. The internet survey mode was the most cost-effective method of collecting
      the target sample size of 400 responses. Sensitivity analysis showed that as the
      target number of responses increased the cost advantage of internet over the mail
      only and mixed mode surveys increased because of the low marginal cost associated
      with extending additional invitations.

PMID- 29367141
TI  - Combined heterogeneous Electro-Fenton and biological process for the treatment of
      stabilized landfill leachate.
AB  - Treatment of stabilized landfill leachate is a great challenge due to its poor
      biodegradability. Present study made an attempt to treat this wastewater by
      combining electro-Fenton (E-Fenton) and biological process. E-Fenton treatment
      was applied prior to biological process to enhance the biodegradability of
      leachate, which will be beneficial for the subsequent biological process. This
      study also investigates the efficiency of iron molybdophosphate (FeMoPO)
      nanoparticles as a heterogeneous catalyst in E-Fenton process. The effects of
      initial pH, catalyst dosage, applied voltage and electrode spacing on Chemical
      Oxygen Demand (COD) removal efficiency were analyzed to determine the optimum
      conditions. Heterogeneous E-Fenton process gave 82% COD removal at pH 2, catalyst
      dosage of 50 mg/L, voltage 5 V, electrode spacing 3 cm and electrode area 25 cm2.
      Combined E-Fenton and biological treatment resulted an overall COD removal of
      97%, bringing down the final COD to 192 mg/L.

PMID- 29367142
TI  - A case for the commons: The Snow Crab in the Barents.
AB  - Closing of the marine commons increases economic returns and slows depletion of
      valuable ocean resources. Rights-based management is widely used for fisheries
      rationalization. Regulators with sound biological and economic information can in
      theory set overall harvest control rules that protect the fish stocks, and manage
      for external costs and benefits from harvest. These may include ecosystem
      damages, overcapitalization in the fishery, and/or equity concerns. Regulatory
      efforts and related rights-based management instruments may increase the returns
      to fishery stakeholders but miss important challenges that are increasing under
      climate change. These include transboundary resource management and tradeoffs
      between local economic returns and Total Economic Value. The case of the
      valuable, yet invasive, crab species, Chionoecetes Opilio (Snow Crab) in the
      Barents Sea illustrates the concerns. The spread of the crab has known and
      unknown ecosystem and commercial fishery risks, particularly to uncertain
      ecosystem values. We show how the progression of the biological invasion
      interacts with human strategic behavior to identify limitations of management
      options. Open access harvesting of the species in international waters has
      generated a positive spillover effect by slowing the westward spread of the
      species to sensitive benthic ecosystems. This benefit is threatened by
      reclassification of the crab as a "sedentary species" (one which is not capable
      of leaving the seabed when harvestable (UNCLOS, 1982, article 77, part VI)). This
      shifts the regulatory environment for the crab in ways that exacerbate the
      invasion in exchange for protection of local gains. Such problems will increase
      in magnitude and impact as climate changes increasingly affect species' ranges.
      Optimal decision-making regarding profitable species in new ecosystems must
      incorporate how strategic institutional shifts occurring in response to the
      economic incentives asymmetrically affect local and global stakeholders in
      addition to standard concerns over ecological and economic damages.

PMID- 29367143
TI  - A full-scale comparison of two hybrid constructed wetlands treating domestic
      wastewater in Pakistan.
AB  - Objective of the current work was to monitor the year-round response of full
      scale hybrid constructed-wetlands (CWs) treating domestic wastewater under
      variable continuous flow. Two systems were evaluated: system-I consisted of an
      anaerobic baffled reactor (ABR) followed by a saturated vertical subsurface-flow
      (VSSF) CW and a free-water-surface (FWS) CW as a tertiary treatment; system-II
      consisted of an ABR followed by a horizontal subsurface-flow (HSSF) CW and FWS.
      Maximum reduction of 80 and 78%, 81 and 82%, 63 and 69%, 79 and 89% for chemical
      oxygen demand (COD), biological oxygen demand (BOD), total kjeldahl nitrogen
      (TKN) and total suspended solids (TSS) was achieved in Systems I and II
      respectively. There was also effective removal (94% and 93%) of the bacterial
      population in both systems while more than 94% of pathogenic microorganisms were
      removed. Data from both systems were further used to compute the first-order rate
      constants for the k-C* model commonly used in CW design. The treatment
      performance was confirmed to follow a first-order reaction rate, in which the k20
      values of chemical oxygen demand (COD), biological oxygen demand (BOD), total
      kjeldahl nitrogen (TKN), total phosphorus (TP) and total suspended solids were
      calculated as 165, 117, 133, 7.5 and 78 m yr-1 respectively for VSSF and 226,
      134, 199, 22 and 73 m yr-1 respectively for HSSF. A positive correlation with
      temperature was discovered for all parameters in both systems.

PMID- 29367144
TI  - A clinical-grade gene therapy vector for pharmacoresistant epilepsy successfully
      overexpresses NPY in a human neuronal cell line.
AB  - PURPOSE: Epilepsy is a common neurological condition characterised by recurrent
      unprovoked seizures and often treatable with appropriate medication. However,
      almost 30% of cases are pharmacoresistant and while a proportion of these may be
      amenable to resective surgery, a gene therapy approach could be an attractive
      alternative option. Neuropeptide Y (NPY) has anticonvulsant and anti
      epileptogenic properties in animal models of temporal lobe epilepsy when
      delivered by an adeno-associated viral (AAV) vector. Here we sought to
      demonstrate successful secretion of NPY from AAV-transduced human neuronal cells,
      which would be essential in planning any clinical trial. METHODS: A human
      neuroblastoma cell line (SH-SY5Y) was used to assess in vitro whether an AAV
      vector manufactured to clinical-grade protocols would be effective at transducing
      these cells to express NPY. Optimal transduction efficiency was first achieved
      with retinoic acid and tetradecanoylphorpol-13-acetate (TPA) treatment, prior to
      expose to AAV1-green fluorescent protein (GFP) reporter vector, AAV1-NPY
      therapeutic vector or sham treated with no vector. Levels of NPY in cell
      supernatants were determined using two antibody-based methods RESULTS: We found
      that the levels of NPY released into the cell culture media supernatant, and
      protein extracts of the cell pellet, were significantly higher following exposure
      to AAV1-NPY than when compared to either a control GFP reporter vector (AAV1-GFP)
      or sham treated controls. CONCLUSION: This first demonstration that an AAV-NPY
      construct can successfully transduce human neuronal cells supports the pre
      clinical development of a clinical trial using AAV-based NPY for
      pharmacoresistant epilepsy.

PMID- 29367145
TI  - Pre-ictal heart rate changes: A systematic review and meta-analysis.
AB  - PURPOSE: To estimate the incidence of pre-ictal heart rate (HR) manifestations
      and to identify clinical and study-related factors modulating the estimate.
      METHODS: We searched articles recording concurrent pre-ictal EEG and HR in adults
      and children with epilepsy. Pre-ictal HR changes were classified as HR reduction
      (HRR) or increase (HRI). Studies reporting the total number of seizures and the
      number of seizures with pre-ictal HR changes were included in a random-effects
      meta-analysis. A random-effects meta-regression was used to identify variables
      affecting study heterogeneity. RESULTS: Thirty studies, including 1110
      participants and 2957 seizures, were included. The meta-analysis showed a pooled
      incidence of pre-ictal HRI of 36/100 seizures (95% CI 22-50). The pre-ictal HRI
      incidence was 44/100 seizures (95% CI 33-55) in studies including temporal lobe
      epilepsy, 55/100 seizures (95% CI 41-68) in studies enrolling adults and 35/100
      seizures (95% CI 16-58) when patients on antiepileptic drugs were included. The
      meta-regression showed that the age group, the length of the pre-ictal period,
      the incidence of ictal tachycardia and the time of onset of the pre-ictal HRI had
      a significant impact on estimates variability. The pooled incidence of pre-ictal
      HRR was 0/100 seizures (95% CI 0-1). CONCLUSION: Review of bias evaluation and
      methods assessment disclosed several major limitations in the evidence-base. HR
      monitoring could be valuable to identify seizures prior to their apparent onset,
      opening the possibility to early interventions. Additional effort is necessary to
      delineate the target population who might benefit from its use and the mechanisms
      sustaining the pre-ictal cardiac changes.

PMID- 29367146
TI  - Surface active gold nanoparticles biosynthesis by new approach for
      bionanocatalytic activity.
AB  - In the present day, nanotechnology is one of the most promising leading
      scientific and potentials areas in modern key technology development toward to
      the humankind. The synthesis of noble metal nanoparticles (NPs) is an expanding
      research area due to the possible applications for the development of bio-medical
      applications. Eco-friendly approach for the biosynthesis of gold nanoparticles
      (AuNPs) using the aqueous extract from Ruellia tuberosa and Phyllanthus acidus
      (leaf and twig) for the first time. Surface active AuNPs were characterized by UV
      Vis spectroscopy, FTIR (Fourier transform infrared) spectroscopy, DSC
      (differential scanning colorimetry), DLS (dynamic light scattering) and
      environmental SEM (scanning electron microscope) analysis at room temperature
      (RT). Enhanced surface plasmon resonance (SPR) absorbance UV visible optical
      spectra were detected in the range of 552, 548, 558 and 536 nm. SEM and DLS
      (transmission mode) analysis confirmed the morphology of the nanoparticles to be
      spherical with the average size in the range of 88.37, 94.31, 82.23 and 81.36 nm.
      Further they have enhanced the enzyme activity on alpha-amylase, cellulase, and
      xylanase. The results suggest that the phyto-fabricated AuNPs from R. tuberosa
      and P. acidus is simple, less expensive, eco-friendly, green synthesis and also
      can be exploited for the potential future industrial and bio-medical
      applications.

PMID- 29367147
TI  - Mixed microalgae consortia growth under higher concentration of CO2 from
      unfiltered coal fired flue gas: Fatty acid profiling and biodiesel production.
AB  - Biodiesel is produced by transesterification of fatty acid methyl esters (FAME)
      from oleaginous microalgae feedstock. Biodiesel fuel properties were studied and
      compared with biodiesel standards. Qualitative analysis of FAME was done while
      cultivating mixed microalgae consortia under three concentrations of coal fired
      flue gas (1%, 3.0% and 5.5% CO2). Under 1% CO2 concentration (flue gas), the FAME
      content was 280.3 MUg/mL, whereas the lipid content was 14.03 MUg/mL/D (day).
      Both FAMEs and lipid contents were low at other CO2 concentrations (3.0 and
      5.5%). However, mixed consortia in the presence of phosphate buffer and flue gas
      (PB + FG) showed higher saturated fatty acids (SFA) (36.28%) and unsaturated
      fatty acids (UFA) (63.72%) versus 5.5% CO2 concentration, which might be
      responsible for oxidative stability of biodiesel. Subsequently, higher cetane
      number (52) and low iodine value (136.3 gI2/100 g) biodiesel produced from mixed
      consortia (PB + FG) under 5.5% CO2 along with 50 mM phosphate buffer were found
      in accordance with European (EN 14214) standard. Results revealed that phosphate
      buffer significantly enhanced the biodiesel quality, but reduced the FAME yield.
      This study intended to develop an integrated approach for significant improvement
      in biodiesel quality under surplus phosphorus by utilizing waste flue gas (as CO2
      source) using microalgae. The CO2 sequestration from industrial flue gas not only
      reduced greenhouse gases, but may also ensure the sustainable and eco-benign
      production of biodiesel.

PMID- 29367148
TI  - Proposal for verifying dipole properties of light-harvesting antennas.
AB  - For light harvesters with a reaction center complex (LH1-RC complex) of three
      types, we propose an experiment to verify our analysis based upon antenna
      theories that automatically include the required structural information. Our
      analysis conforms to the current understanding of light-harvesting antennas in
      that we can explain known properties of these complexes. We provide an
      explanation for the functional roles of the notch at the light harvester, a
      functional role of the polypeptide called PufX or W at the opening, a functional
      role of the special pair, a reason that the cross section of the light harvester
      must not be circular, a reason that the light harvester must not be spherical,
      reasons for the use of dielectric bacteriochlorophylls instead of conductors to
      make the light harvester, a mechanism to prevent damage from excess sunlight, an
      advantage of the dimeric form, and reasons for the modular design of nature.
      Based upon our analysis we provide a mechanism for dimerization. We predict that
      the dimeric form of light-harvesting complexes is favored under intense sunlight.
      We further comment upon the classification of the dimeric or S-shape complexes.
      The S-shape complexes should not be considered as the third type of light
      harvester but simply as a composite form.

PMID- 29367149
TI  - Marine fungal DHICA as a UVB protectant: Assessment under in vitro and in vivo
      conditions.
AB  - The present study explores UVB protective role of a melanin precursor namely
      DHICA (5,6- Dihydroxyindole-2-carboxylic acid) expressed by the marine imperfect
      fungus Aspergillus nidulans. In brief, A. nidulans grown in a modified growth
      medium for the period of 5 days at 25  degrees C under shaking conditions and the
      extracellular medium free from fungal biomass used for the extraction of DHICA.
      The extracted DHICA further exposed to partial purification and subjected to UVB
      protection studies using HaCaT cells and Balb/c mice independently. DHICA
      obtained in the present study found soluble in water. Experiments on HaCaT cell
      compatibility revealed nil cell death up to 500 MUM concentration of DHICA. UVB
      protection studies under in vitro conditions emphasizes DHICA significantly
      protect HaCaT cells from UVB exposure by quenching the generated ROS, reducing
      cell apoptosis, maintain the cellular integrity and sequentially down regulating
      the LPO (Lipid peroxidation) and up-regulating the antioxidant enzyme (SOD
      (Superoxide Dismutase), Catalase, GPx (Glutathione peroxidase)) respectively.
      Further, experiments on cell cycle arrest analysis, gelatin zymography, and
      western blot analysis on COX-2 and TNF-alpha, IHC (Immunohistochemistry) on
      apoptotic markers (Bax, Bcl2) substantiate the protective role of DHICA.
      Furthermore, in vivo studies on BALB/c mice carried out and compared with the
      sunscreen cream with sun protective factor (SPF) of 20. Analysis of skin sections
      of experimental samples revealed that an appreciable reduction in the epidermal
      thickness of the skin samples of mice pre-exposed to DHICA followed by UVB
      exposure compared to UVB exposure alone. RT-PCR results on various inflammatory
      apoptotic markers also suggested that DHICA has UVB protective potential. The
      observations made in the present study explore the possible application of DHICA
      alone as a sun-protective agent for skin care.

PMID- 29367150
TI  - Improving implementation of the smoking cessation guidelines with pregnant women:
      How to support clinicians?
AB  - OBJECTIVE: this study aimed to explore the enablers and barriers to
      implementation of the Australian smoking cessation in pregnancy guidelines. These
      guidelines direct clinicians to follow the 5As of cessation: Ask, Advise, Assess,
      Assist and Arrange follow-up. DESIGN: semi-structured interviews based on the
      Theoretical Domains Framework (TDF) elicited clinicians' views and experiences of
      implementing the guidelines. SETTING: antenatal care in the NSW public health
      system. PARTICIPANTS: 27 maternity service managers, obstetricians and midwives.
      FINDINGS: participants confirmed that implementation of the smoking cessation
      guidelines was sub-optimal. This was particularly the case with Assist and
      Arrange follow up at the initial visit, and with following any of the 5As at
      subsequent visits. Key barriers included systems which did not support
      implementation or monitoring, lack of knowledge, skills and training, perceived
      time restrictions, 'difficult conversations' and perceiving smoking as a social
      activity. Enablers included clinicians' knowledge of the harms of smoking in
      pregnancy, clinicians' skills in communicating with pregnant women, positive
      emotions, professional role and identity, the potential of training and of
      champions to influence practice, and systems that regulated behaviour. KEY
      CONCLUSIONS: these findings will contribute to the development of a multifaceted
      intervention to support clinicians in implementing the guidelines. IMPLICATIONS
      FOR PRACTICE: Building on existing strengths, antenatal care providers may be
      supported in implementing the guidelines by working with systems which remind and
      support implementation, the clear reframing of smoking as an addiction, knowledge
      and skills development and by realizing the potential of leadership to maximise
      the impact of reinforcement and social influence.

PMID- 29367152
TI  - Rediscovery of the Testate Amoeba Genus Penardeugenia (Thaumatomonadida,
      Imbricatea).
AB  - The genus Penardeugenia DEFLANDRE 1958 accommodates a single species which was
      described as Pamphagus bathybioticus PENARD 1904. Although this species seems to
      be well characterized in its description, it has never been recorded again.
      Despite its possession of silica scales, it was assigned to the scale-lacking
      Chlamydophryidae (Thecofilosea, Cercozoa). We here present morphological data of
      three isolates. One of them was successfully cultured and enabled the
      amplification of its SSU rDNA sequence. Molecular analyses revealed the
      evolutionary origin of Penardeugenia in the scale-bearing flagellate class
      Thaumatomonadida, which is backed up by morphological similarities of their
      scales. We consider Penardeugenia to represent a closely related genus to
      Thaumatomastix, which apparently lost its ability to form flagella. We describe
      two new species from Germany, P. huelsmannii and P. hausmannii.

PMID- 29367151
TI  - A New Classification of the Dictyostelids.
AB  - Traditional morphology-based taxonomy of dictyostelids is rejected by molecular
      phylogeny. A new classification is presented based on monophyletic entities with
      consistent and strong molecular phylogenetic support and that are, as far as
      possible, morphologically recognizable. All newly named clades are diagnosed with
      small subunit ribosomal RNA (18S rRNA) sequence signatures plus morphological
      synapomorphies where possible. The two major molecular clades are given the rank
      of order, as Acytosteliales ord. nov. and Dictyosteliales. The two major clades
      within each of these orders are recognized and given the rank of family as,
      respectively, Acytosteliaceae and Cavenderiaceae fam. nov. in Acytosteliales, and
      Dictyosteliaceae and Raperosteliaceae fam. nov. in Dictyosteliales. Twelve genera
      are recognized: Cavenderia gen. nov. in Cavenderiaceae, Acytostelium,
      Rostrostelium gen. nov. and Heterostelium gen. nov. in Acytosteliaceae,
      Tieghemostelium gen. nov., Hagiwaraea gen. nov., Raperostelium gen. nov. and
      Speleostelium gen. nov. in Raperosteliaceae, and Dictyostelium and
      Polysphondylium in Dictyosteliaceae. The "polycephalum" complex is treated as
      Coremiostelium gen. nov. (not assigned to family) and the "polycarpum" complex as
      Synstelium gen. nov. (not assigned to order and family). Coenonia, which may not
      be a dictyostelid, is treated as a genus incertae sedis. Eighty-eight new
      combinations are made at species and variety level, and Dictyostelium ammophilum
      is validated.

PMID- 29367153
TI  - Ploidy and Number of Chromosomes in the Alveolate Alga Chromera velia.
AB  - Chromera velia is an alveolate alga which represents the closest known
      phototrophic relative to apicomplexan parasites. Although the nuclear,
      mitochondrial, and plastid genomes of this alga have been sequenced, the number
      of chromosomes and ploidy of C. velia are unknown. We explored ploidy in the
      vegetative cell, the predominant stage in cultures of Chromera, using the
      tyramide signal amplification-fluorescence in situ hybridization (TSA-FISH) in
      isolated nuclei of C. velia. Probes were derived from three single copy genes
      coding for 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDP-ME) kinase, 2-C-methyl
      D-erythritol 2,4-cyclodiphosphate (MEcPP) synthase and Topoisomerase II. Our
      results indicate that the vegetative cell of C. velia is haploid, as each probe
      produced a single fluorescent signal, although the possibility of diploidy with
      somatic pairing of homologous chromosomes cannot be completely excluded.
      Restriction analysis and hybridization with the telomere probe produced eight
      bands suggesting the presence of four chromosomes in haploid vegetative cells of
      C. velia. However, when the chromerid-specific telomere probe (TTTAGGG)4 was used
      for TSA-FISH, we consistently obtained a double signal. This may indicate that
      the four chromosomes are organized in clusters in interphase nuclei of C. velia,
      which is a chromosome organization similar to that of their apicomplexan
      relatives.

PMID- 29367154
TI  - Rationally designed MoS2/protonated g-C3N4 nanosheet composites as photocatalysts
      with an excellent synergistic effect toward photocatalytic degradation of organic
      pollutants.
AB  - The positively charged ultrathin g-C3N4 nanosheets are prepared by ultrasonic
      assisted exfoliation of the protonated g-C3N4. Compared with the protonated g
      C3N4 and exfoliated g-C3N4, the positively charged ultrathin g-C3N4 has abundant
      functional groups as well as desired dispersibility in deionized water, thus it
      could serve as a basic building block for designing related heterojunction
      composites. To take a full advantage of these features, the positively charged
      ultrathin g-C3N4/MoS2 composites are fabricated through a simple electrostatic
      adsorption and self-assembly process followed by a hydrothermal method. By
      loading an appropriate amount of MoS2 on the ultrathin g-C3N4 nanosheets, the as
      fabricated composites exhibit considerable improvement on the photocatalytic
      activities toward the degradation of typical organic pollutants (i.e., methyl
      orange and phenol) under visible light irradiation. The composite containing 2
      wt% MoS2 shows the highest efficiency of about 96.5% for the methyl orange
      degradation, which is about 3.5 times and 8 times compared to those of the
      positively charged ultrathin g-C3N4 and bulk g-C3N4, respectively. The superb
      photocatalytic performance benefits from the unique advantages, including richly
      available reaction sites, aligned energy levels between g-C3N4 and the MoS2, and
      efficient electron transfer. This work opens new possibilities for the rational
      design and construction of the g-C3N4 based composites as highly efficient and
      stable visible-light driven photocatalysts for the degradation of organic
      pollutants.

PMID- 29367155
TI  - The role of ozone pretreatment on optimization of membrane bioreactor for
      treatment of oil sands process-affected water.
AB  - Previously, anoxic-aerobic membrane bioreactor (MBR) coupled with mild ozonation
      pretreatment has been applied to remove toxic naphthenic acids (NAs) in oil sands
      process-affected water (OSPW). To further improve MBR performance, the optimal
      operation conditions including hydraulic retention time (HRT) and initial ammonia
      nitrogen (NH4+-N) need to be explored. In this study, the role of ozone
      pretreatment on MBR optimization was investigated. Compared with MBR treating raw
      OSPW, MBR treating ozonated OSPW had the same optimal operation conditions (HRT
      of 12 h and NH4+-N concentration of 25 mg/L). Nevertheless, MBR performance
      benefited from HRT adjustment more after ozone pretreatment. HRT adjustment
      resulted in NA removal in the range of 33-50% for the treatment of ozonated OSPW
      whereas NA removal for raw OSPW only fluctuated between 27% and 38%. Compared
      with the removal of classical NAs, the degradation of oxidized NAs was more
      sensitive to the adjustment of operation conditions. Adjusting HRT increased the
      removal of oxidized NAs in ozonated OSPW substantially (from 6% to 35%). It was
      also noticed that microbial communities in MBR treating ozonated OSPW were more
      responsive to the adjustment of operation conditions as indicated by the
      noticeable increase of Shannon index and extended genetic distances.

PMID- 29367156
TI  - Liquid-liquid extraction and facilitated transport of f-elements using an N-pivot
      tripodal ligand.
AB  - Diglycolamide (DGA)-functionalized tripodal ligands offer the required nine
      coordinated complex for effective binding to a trivalent lanthanide/actinide ion.
      A N-pivot tripodal ligand (TREN-DGA) containing three DGA pendant arms was
      evaluated for the extraction and supported liquid membrane transport studies
      using PTFE flat sheets. Solvent extraction studies indicated preferential
      extraction of 1:1 (M:L) species, while the metal ion extraction increased with
      increasing HNO3 concentration conforming to a solvated species extraction. Flat
      sheet-supported liquid membrane studies, carried out using 4.0 * 10-3 M TREN-DGA
      in 95% n-dodecane + 5% iso-decanol indicated faster mass transport for Eu3+ ion
      as compared to Am3+ ion. The determined transport parameters indicated slow
      diffusion of the M-TREN-DGA (M = Am or Eu) complex being the rate-determining
      step. The transport of lanthanides and actinides followed the trend: Eu3+ > Am3+~
      Pu4+ >> UO22+ and Am can be selectively separated from a mixture of U and Pu by
      oxidizing the latter to its +6 oxidation state. The liquid membrane stability was
      not encouraging and was deteriorating the transport efficiency with time, which
      was attributed to carrier loss into the aqueous phases.

PMID- 29367157
TI  - Comparative analyses of microbial structures and gene copy numbers in the
      anaerobic digestion of various types of sewage sludge.
AB  - Anaerobic co-digestion of various sewage sludges is a promising approach for
      greater recovery of energy, but the process is more complicated than mono
      digestion of sewage sludge. The applicability of microbial structure analyses and
      gene quantification to understand microbial conditions was evaluated. The results
      show that information from gene analyses is useful in managing anaerobic co
      digestion and damaged microbes in addition to conventional parameters like total
      solids, pH and biogas production. Total bacterial 16S rRNA gene copy numbers are
      the most useful tools for evaluating unstable anaerobic digestion of sewage
      sludge, rather than mcrA and total archaeal 16S rRNA gene copy numbers, and high
      throughput sequencing. First order decay rates of gene copy numbers during pH
      failure were higher than typical decay rates of microbes in stable operation. The
      sequencing analyses, including multidimensional scaling, showed very different
      microbial structure shifts, but the results were not consistent.

PMID- 29367158
TI  - Operation of a vertical algal biofilm enhanced raceway pond for nutrient removal
      and microalgae-based byproducts production under different wastewater loadings.
AB  - In this study, a vertical-algal-biofilm-enhanced raceway pond (VAB-enhanced
      raceway pond) was designed and assessed for wastewater treatment and algal
      biomass production under different nutrient loading rates. Results indicated that
      the maximum removal capacity of the system was accordingly 7.52, 6.76 and 0.11
      g.m-2.day-1 for COD, TN and TP, under which the wastewater effluent concentration
      could be respectively reduced from 106.00, 92.71 and 1.48 mg/L to 43.5, 11.03 and
      0.46 mg/L in continuous mode. Meanwhile, about 7.47-10.10 t.ha-1.year-1 of lipid,
      14.85-23.01 t.ha-1.year-1 of protein and 10.69-14.20 t.ha-1.year-1 of
      carbohydrate could be produced from the algae by the system in large scale. The
      corresponding estimated stoichiometric-methane-potential and biodiesel production
      of the harvested biomass was 21,471-29,136 m3.ha-1.year-1 and 0.57-1.15 t.ha
      1.year-1, respectively. The findings of this study demonstrate the feasibility of
      using VAB-enhanced raceway pond for economically and cost-effectively recovery of
      nutrients from the wastewater via algal-based byproducts production.

PMID- 29367159
TI  - Target discovery of cytotoxic withanolides from Physalis angulata var. villosa
      via reactivity-based screening.
AB  - The reactivity-based screening (RBS) was developed for directed discovery of
      cytotoxic withanolides. In this study, a thiol probe, 4-chlorobenzenethiol, was
      used to selectively attack cytotoxic withanolides containing potential
      pharmacophore, 2(3)-en-1-one in ring A (AEO) and 5beta,6beta-epoxy in ring B
      (BE), from the plant extract of Physalis angulata var. villosa. The screening was
      performed based on the potential mechanism of 4-chlorobenzenethiol nucleophilic
      addition to AEO, followed by detection of adducts using liquid chromatography
      quadrupole-time-of-flight mass spectrometry (LC-Q-TOF-MS). Guided by RBS, eleven
      target withanolides, including five new compounds, physagulides R-V (10-14) and
      six known ones (2, 7-9, 15, 16) were discovered. All of them exhibited
      cytotoxicity against the both tested cell lines, especially, compounds 2, 7, 8
      and 14 showed potent activities with IC50 values of 1.57-6.29 MUM. The results
      suggested that RBS was efficient and accurate for rapid identification of
      cytotoxic withanolides and could guide isolation of target components from the
      complex medicinal plant extract.

PMID- 29367160
TI  - Gas-phase structural characterization of neuropeptides Y Y1 receptor antagonists
      using mass spectrometry: Orbitrap vs triple quadrupole.
AB  - Collision induced dissociation of triple quadrupole mass spectrometer (CID-QqQ)
      and high-energy collision dissociation (HCD) of Orbitrap were compared for four
      neuropeptides Y Y1 (NPY Y1) receptor antagonists and showed similar qualitative
      fragmentation and structural information. Orbitrap high resolution and high mass
      accuracy HCD fragmentation spectra allowed unambiguous identification of product
      ions in the range 0.04-4.25 ppm. Orbitrap mass spectrometry showed abundant
      analyte-specific product ions also observed on CID-QqQ. These results show the
      suitability of these product ions for use in quantitative analysis by MRM mode.
      In addition, it was found that all compounds could be determined at levels >1 MUg
      L-1 using the QqQ instrument and that the detection limits for this analyzer
      ranged from 0.02 to 0.6 MUg L-1. Overall, the results obtained from experiments
      acquired in QqQ show a good agreement with those acquired from the Orbitrap
      instrument allowing the use of this relatively inexpensive technique (QqQ) for
      accurate quantification of these compounds in clinical and academic applications.

PMID- 29367161
TI  - Cathepsin D immobilized capillary reactors for on-flow screening assays.
AB  - The treatment of diseases using enzymes as targets has called for the development
      of new and reliable methods for screening. The protease cathepsin D is one such
      target involved in several diseases such as tumors, degenerative processes, and
      vital processes of parasites causing schistosomiasis. Herein, we describe the
      preparation of a fused silica capillary, cathepsin D (CatD)-immobilized enzyme
      reactor (IMER) using in a multidimensional High Performance Liquid Chromatography
      based method (2D-HPLC) and zonal affinity chromatography as an alternative in the
      search for new ligands. The activity and kinetic parameters of CatD-IMER were
      evaluated by monitoring the product MOCAc-Gly-Lys-Pro-Ile-Leu-Phe (P-MOCAc) (KM =
      81.9 +/- 7.49 MUmol/L) generated by cleavage of the fluorogenic substrate MOCAc
      Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-d-Arg-NH2 (S-MOCAc). Stability
      studies have indicated that CatD-IMER retained 20% of activity after 5 months, a
      relevant result, because proteases are susceptible to autoproteolysis in solution
      assays with free enzyme. In the search for inhibitors, 12 crude natural product
      extracts were analyzed using CatD-IMER as the target, resulting in the isolation
      of different classes of natural products. In addition, 26 compounds obtained from
      different species of plants were also screened, demonstrating the efficiency and
      reproducibility of the herein reported assay even in the case of complex matrices
      such as plant crude extracts.

PMID- 29367162
TI  - Surface modification by carboxymethy chitosan via pad-dry-cure method for binding
      Ag NPs onto cotton fabric.
AB  - To obtain durably antimicrobial cotton fabric, carboxymethyl chitosan (CMC) was
      covalently linked to cotton fibers via an esterification with the cellulose
      hydroxyl groups, and the silver nanoparticles (Ag NPs) were adhered to the fiber
      surface by the coordination bonds with the amino groups of CMC. The finished
      cotton fabrics have an excellent antibacterial function and outstanding
      laundering durability. Even after 50 consecutive laundering tests, the modified
      cotton fabrics still show satisfactory bacterial reduction rates (BR) against
      both S. aureus and E. coli, which are all higher than 94%. These findings allow
      for broader applications of antimicrobial cotton textiles with a decreased safety
      risk and lower environmental impact arise from the Ag NPs.

PMID- 29367163
TI  - Recent insights in microbial exopolysaccharide biosynthesis and engineering
      strategies.
AB  - The distinct biosynthesis pathways for microbial exopolysaccharide production
      provide different engineering strategies to tailor the chemical structures of the
      final polymers. This review focuses on the latest insights in the various
      pathways and identifies bottlenecks as well as promising targets for tailoring
      microbial polysaccharide production. The main engineering strategies includes the
      combinatorial assembly of glycosyltransferases and engineering of the Wzx and Wzy
      proteins for flipping of repeating units as well as polymerization. In the case
      of synthase based polysaccharides, the use of epimerases or engineering
      approaches of the synthase itself as well as overexpression of c-di-GMP levels is
      identified as one of the most promising strategies. For sucrase-based
      biosynthesis, the in vitro production by engineered sucrase enzymes or adjusted
      production conditions is shown as a very promising method.

PMID- 29367164
TI  - Integrated viral clearance strategies-reflecting on the present, projecting to
      the future.
AB  - Viral clearance and inactivation are critical steps in ensuring the safety of
      biological products derived from mammalian cell culture and are a component of an
      adventitious agent control strategy which spans both upstream and downstream
      processes. Although these approaches have been sufficient to support the
      development of biologics to date, the empirical and semi-quantitative nature of
      the approach leaves some potential gaps. For example, the concept of performing a
      quantitative risk assessment for the downstream components of virus safety was
      introduced in ICH Q5A for XMuLV. An ideal future state would be to perform a
      similar quantitative risk assessment for a range of viruses based on an
      assessment of potential virus risk in both upstream and downstream processes.
      This assessment combined with an integrated control strategy (including
      monitoring) would be extremely beneficial in minimizing potential adventitious
      agent risks. Significant progress has been achieved towards this goal in the last
      several years including recent advances in quantification of virus sequences in
      cell banks (ADVTIG), development of truly modular or generic viral clearance
      claims for specific unit operations, enhanced controls of upstream media
      (HTST/nanofiltration) and the use of RVLP for in-process monitoring. The recent
      shift towards continuous processing has the potential to enhance the criticality
      of in-line monitoring and the complexity of viral clearance and inactivation
      (owing to a wide range of potential 'worst case' viral clearance scenarios).
      However, gaps exist in, firstly, the ability to quantify potential virus risk
      levels in process streams in real-time, secondly, mechanistic understanding of
      virus/chromatography media interactions, and thirdly, mechanistic understanding
      of virus/filter interactions. Some new technologies may also need to be developed
      to allow for real-time confirmation of virus inactivation and clearance to
      support process development (both batch and continuous) and assessment of the
      impact of process deviations during manufacturing. This review paper provides an
      overview of the current state of an overall integrated control strategy for
      upstream and downstream processing and highlights the investments that could be
      pursued to achieve the future state of a quantitative virus risk assessment for a
      range of viruses. One potential approach to address these gaps is the use of data
      mining from large, comprehensive and diverse data sets to establish heuristic
      rules for virus detection, clearance and inactivation followed by specific
      hypothesis-driven experiments for cases that fall outside of the normal paradigm.
      Once this approach reaches a mature state suitable for implementation, there is
      an opportunity to update regulatory guidance (e.g. ICH Q5A) accordingly.

PMID- 29367165
TI  - Evaluation of afferent pain pathways in adrenomyeloneuropathic patients.
AB  - OBJECTIVE: Patients with adrenomyeloneuropathy may have dysfunctions of visual,
      auditory, motor and somatosensory pathways. We thought on examining the
      nociceptive pathways by means of laser evoked potentials (LEPs), to obtain
      additional information on the pathophysiology of this condition. METHODS: In 13
      adrenomyeloneuropathic patients we examined LEPs to leg, arm and face
      stimulation. Normative data were obtained from 10 healthy subjects examined in
      the same experimental conditions. We also examined brainstem auditory evoked
      potentials (BAEPs), pattern reversal full-field visual evoked potentials (VEPs),
      motor evoked potentials (MEPs) and somatosensory evoked potentials (SEPs).
      RESULTS: Upper and lower limb MEPs and SEPs, as well as BAEPs, were abnormal in
      all patients, while VEPs were abnormal in 3 of them (23.1%). LEPs revealed
      abnormalities to stimulation of the face in 4 patients (30.7%), the forearm in 4
      patients (30.7%) and the leg in 10 patients (76.9%). CONCLUSIONS: The pathologic
      process of adrenomyeloneuropathy is characterized by a preferential involvement
      of auditory, motor and somatosensory tracts and less severely of the visual and
      nociceptive pathways. This non-inflammatory distal axonopathy preferably damages
      large myelinated spinal tracts but there is also partial involvement of small
      myelinated fibres. SIGNIFICANCE: LEPs studies can provide relevant information
      about afferent pain pathways involvement in adrenomyeloneuropathic patients.

PMID- 29367166
TI  - Development, validation and utility of a simulation model of the nociceptive
      flexion reflex threshold.
AB  - OBJECTIVE: A variety of algorithms is used for nociceptive flexion reflex
      threshold (NFRT) estimation, but their estimation accuracy is unknown. We
      developed a computer based simulation model of the NFRT to quantify and compare
      the accuracy of available estimation algorithms. METHODS: This simulation model
      is based on basic characteristics of the NFRT and specified by data collected
      from 60 healthy volunteers. We validated the model by comparing simulated data
      with data obtained independently in another volunteer population. The model was
      used to quantify the accuracy of previously published NFRT estimation algorithm
      for three NFRT variabilities representing sensory deprivation, distraction and
      general anaesthesia. RESULTS: The dynamic staircase algorithm obtained most
      accurate NFRT estimates during all NFRT variabilities. The number of stimuli
      applied can be chosen higher to increase estimate precision or lower to reduce
      measurement time. CONCLUSIONS: Our simulation model is a valid tool to measure
      the accuracy of NFRT estimation algorithms. It can be applied to analyse and
      develop algorithms. The dynamic staircase algorithm shows the highest precision
      in NFRT estimation and is recommended for NFRT studies. SIGNIFICANCE: Using
      optimized NFRT estimation algorithms increases precision in clinical and
      experimental NFRT studies and might therefore reduce the measurement effort
      necessary.

PMID- 29367167
TI  - Long-term experience with a novel uterine-sparing transvaginal mesh procedure for
      uterovaginal prolapse.
AB  - OBJECTIVES: To evaluate outcomes and quality of life in patients operated
      transvaginally with an original mesh shape for uterus-sparing prolapse surgery
      and to demonstrate the safety and efficacy of the technique. STUDY DESIGN: We
      prospectively evaluated 66 postmenopausal patients (POP-Q Stage III: 32, IV: 34)
      operated between May 2008 and December 2013. We used wide weave polypropylene
      monofilament mesh that functions as a hammock anchored posteriorly to
      sacrospinous ligaments, its anterior wings exit the pelvis through the obturatory
      membrane. Follow-up was scheduled at 3-, 12- months and in May 2016. Prolapse
      Quality of Life Questionnaire (P-QoL) was administered preoperatively, at 12
      months and in May 2016. The chi square and Wilcoxon test were used for
      statistical analysis. RESULTS: Mean follow-up was 5.6 (SD: 1.6, Range: 1.1-8.1)
      years. The overall success rate (POP-Q <= 2) was 92.5% at 12 months and 84.4% at
      May 2016, these data remained stable over time (p > 0.05). Early complications
      occurred in 2 (3%) patients, late in 5 (7.8%) of which mesh extrusion in 4
      (6.3%). Data from P-QoL showed significant improvement between preoperative and
      postoperative data (P < 0.01 for all domains) and they remained stable with time
      (p > 0.05). De-novo dyspareunia was 17.6% at 12 months and 10.3% at May 2016.
      CONCLUSIONS: The low rate and grade of complications demonstrates the safety of
      the procedure, which offers stable anatomical correction with significant
      improvement in QoL.

PMID- 29367168
TI  - Does vaginal estriol make urodynamic changes in women with overactive bladder
      syndrome and genitourinary syndrome of menopause?
AB  - OBJECTIVES: OAB is a common finding in postmenopausal women. Hypoestrogenism is
      the root cause of many signs and symptoms of Genitourinary Syndrome of Menopause
      (vaginal dryness, atrophy, dyspareunia, urinary disorders, etc.). As such the aim
      of this study was to evaluate the urodynamic effects of ultralowdose estriol
      vaginal gel formulation to treat women with Genitourinary Syndrome of Menopause
      and Overactive Bladder Syndrome. STUDY DESIGN: This open-labeled, single center,
      prospective study involved 37 women with OAB recruited in our Urogynecological
      Unit between January and July 2016. They received estriol 50 mcg/g vaginal gel,
      one applicator-dose per day for 3 weeks followed by one dose twice a week for 12
      weeks. Objective and subjective parameters were evaluated before and after
      treatment through the urodynamic examination, Overactive Bladder symptom score
      and Short Form Health Survey-36 questionnaires. RESULTS: Vaginal atrophy symptoms
      and signs as well as the overactive bladder subjective symptom parameter improved
      significantly. Urodynamic evaluation showed significant improvement in first
      desire to void and maximum cystometric capacity after estriol usage. Patients who
      had detrusor overactivity did not show any improvement for this parameter after
      treatment. The voiding function parameters did not significantly change. Short
      form-36 showed a better quality of life after treatment especially for the
      emotional role, as well as mental and general health. CONCLUSIONS: A local ultra
      low dose concentration of estriol could be effective in women with vaginal
      atrophy and Overactive Bladder Syndrome for improving both subjective symptoms
      and urodynamic parameters of storage function not affecting voiding function.

PMID- 29367169
TI  - Isolated fetal horseshoe kidney does not seem to increase the risk for abnormal
      chromosomal microarray results.
AB  - OBJECTIVE: To examine the risk for clinically significant chromosomal microarray
      analysis (CMA) among fetuses with apparently isolated horseshoe kidney. METHODS:
      Data from all CMA analyses performed due to isolated horseshoe kidney reported to
      the Israeli Ministry of Health between January 2013 and September 2016 were
      retrospectively obtained from a computerized database. Risk estimation was
      performed comparing the rate of abnormal CMA findings to the general population,
      based on a systematic review encompassing 9272 pregnancies with normal
      ultrasound, and local data cohort of 5541 pregnancies undergoing CMA due to
      maternal request. RESULTS: Of 82 pregnancies with isolated horseshoe kidney, one
      loss-of-copy-number variant compatible with 16p13.11 microdeletion syndrome was
      demonstrated (1.2%). In addition, two variants of unknown significance (VOUS)
      were detected (2.4%). The relative risk for pathogenic CMA findings among
      pregnancies with isolated single horseshoe kidney was not significantly different
      from the control population (1.03-1.39%). DISCUSSION: To our best knowledge, our
      study is the first report describing the rate of clinically significant CMA
      findings in fetuses with isolated horseshoe kidney. The detection of one
      pathogenic CMA findings in our cohort implies that the value of CMA analysis in
      such pregnancies is similar to the general population.

PMID- 29367170
TI  - Application of the 2015 diagnostic criteria for neuromyelitis optica spectrum
      disorders in a cohort of Latin American patients.
AB  - BACKGROUND: The 2015 International Panel for neuromyelitis optica (NMO) spectrum
      disorders (NMOSD) diagnosis (IPND) criteria was recently proposed. However,
      because there are no studies evaluating application of the IPND criteria in Latin
      American populations, we aimed to assess whether these new criteria improve the
      diagnostic rate and reduce the time taken to make the diagnosis in a cohort of
      Latin American patients. METHODS: We reviewed medical records and applied both
      the 2006 and 2015 diagnostic criteria to all patients seen in four centers in
      Argentina, Brazil and Venezuela. Patients with multiple sclerosis (MS, n = 915)
      or other well-established central nervous system (CNS) inflammatory diseases were
      excluded. AQP4-ab status was measured using indirect immunofluorescence (23%) and
      cell-based assay (CBA, 77%). In addition, data on gender, ethnicity, age and
      symptoms at onset, relapses, neuroimaging and immunosuppressive therapy were
      collected. RESULTS: A total of 104 patients were classified as presenting NMOSD
      (2015 IPND). Of these, 64 patients (61.5%) fulfilled the 2006 NMO criteria (32
      AQP4-ab positive, 17 AQP4-ab negative and 15 unknown). Thus, 40 new patients
      (38.5%) were classified as presenting NMOSD using the 2015 IPND criteria (33 AQP4
      ab positive, 5 AQP4-ab negative and 2 unknown AQP4-ab status), with a median time
      taken to fulfill the 2015 NMOSD criteria (n = 104) of 1 month (95% CI: 0.6-1.3)
      and a median time taken to fulfill the 2006 NMO criteria (n = 64) of 18 months
      (95% CI: 9-26) (log-rank test: p < 0.0001). Females, with median age of 37 years,
      white ethnicity and recurrent course, predominated in all samples. Ninety-nine
      patients (95.1%) had at least 1 of the 3 major core clinical characteristics, of
      which optic neuritis (56.7%) was the most frequent symptom at disease onset.
      CONCLUSION: This study showed that there was a 62.5% increase in the rate of
      diagnosing NMOSD through the 2015 IPND criteria, in comparison with the 2006 NMO
      criteria, with a shorter median time to diagnosis.

PMID- 29367171
TI  - The UK National DNA Database: Implementation of the Protection of Freedoms Act
      2012.
AB  - In 2008, the European Court of Human Rights, in S and Marper v the United
      Kingdom, ruled that a retention regime that permits the indefinite retention of
      DNA records of both convicted and non-convicted ("innocent") individuals is
      disproportionate. The court noted that there was inadequate evidence to justify
      the retention of DNA records of the innocent. Since the Marper ruling, the laws
      governing the taking, use, and retention of forensic DNA in England and Wales
      have changed with the enactment of the Protection of Freedoms Act 2012 (PoFA).
      This Act, put briefly, permits the indefinite retention of DNA profiles of most
      convicted individuals and temporal retention for some first-time convicted minors
      and innocent individuals on the National DNA Database (NDNAD). The PoFA regime
      was implemented in October 2013. This paper examines ten post-implementation
      reports of the NDNAD Strategy Board (3), the NDNAD Ethics Group (3) and the
      Office of the Biometrics Commissioner (OBC) (4). Overall, the reports highlight a
      considerable improvement in the performance of the database, with a current match
      rate of 63.3%. Further, the new regime has strengthened the genetic privacy
      protection of UK citizens. The OBC reports detail implementation challenges
      ranging from technical, legal and procedural issues to sufficient understanding
      of the requirements of PoFA by police forces. Risks highlighted in these reports
      include the deletion of some "retainable" profiles, which could potentially lead
      to future crimes going undetected. A further risk is the illegal retention of
      some profiles from innocent individuals, which may lead to privacy issues and
      legal challenges. In conclusion, the PoFA regime appears to be working well,
      however, critical research is still needed to evaluate its overall efficacy
      compared to other retention regimes.

PMID- 29367172
TI  - The pathology of torture.
AB  - Detainees may be subjected to torture and extra-judicial execution by State
      actors and terrorists. But, the pathology of torture has not been well-described.
      This is due to the lack of autopsies performed on victims of torture, mostly due
      to the disposal of the bodies of the victims by their torturers. On this basis,
      the cause of death of detainees subjected to torture is often a matter of
      speculation or remains obscure. This paper provides an overview of the pathology
      of torture based on the authour's experience with the autopsies of torture
      victims. At autopsy, many different types of inflicted injuries may be observed,
      often ranging in severity. However, three recurrent patterns of trauma that are
      the hallmarks of torture were recognized by the authour: (1) blunt impact trauma
      characterized by bruises, patterned injuries, and internal injuries; (2)
      electrical and thermal injuries; and (3) injuries from stress positions that
      occur from prolonged suspension. The most under-recognized form of fatal torture
      are the complications of stress positions related to suspension of the victim's
      body by the upper, or lower extremities. For example, prolonged suspension by
      reverse hanging (suspension of the victim's body by the wrists or forearms with
      the arms extended backward at the shoulder joint) can cause over-stretching and
      necrosis of the muscles of the shoulder, resulting in fatal myoglobinuric renal
      failure. It is essential that autopsies be performed on all detainees who die in
      custody, to determine if torture played a role in death. Furthermore, the true
      nature of the injuries sustained often remains obscure unless a musculocutaneous
      dissection is performed. Specifically, dissection of the back, limbs and the
      soles of the feet, as well as the shoulders and knees is essential to determine
      if specific forms of torture have been applied. This is especially true for fatal
      complications of stress positions. Seeking the truth about the medical
      consequences of fatal torture will raise awareness about torture-related
      injuries, assist in rehabilitation of torture survivors, and strengthen forensic
      humanitarian action.

PMID- 29367173
TI  - Photoanthropometric face iridial proportions for age estimation: An investigation
      using features selected via a joint mutual information criterion.
AB  - Age assessment from images is of high interest in the forensic community because
      of the necessity to establish formal protocols to identify child pornography,
      child missing and abuses where visual evidences are the mostly admissible.
      Recently, photoanthropometric methods have been found useful for age estimation
      correlating facial proportions in image databases with samples of some age
      groups. Notwithstanding the advances, newer facial features and further analysis
      are needed to improve accuracy and establish larger applicability. In this
      investigation, frontal images of 1000 individuals (500 females, 500 males),
      equally distributed in five age groups (6, 10, 14, 18, 22 years old) were used in
      a 10 fold cross-validated experiment for three age thresholds classifications
      (<10, <14, <18 years old). A set of novel 40 features, based on a relation
      between landmark distances and the iris diameter, is proposed and joint mutual
      information is used to select the most relevant and complementary features for
      the classification task. In a civil image identification database with diverse
      ancestry, receiver operating characteristic (ROC) curves were plotted to verify
      accuracy, and the resultant AUCs achieved 0.971, 0.969, and 0.903 for the age
      classifications (<10, <14, <18 years old), respectively. These results add
      support to continuing research in age assessment from images using the metric
      approach. Still, larger samples are necessary to evaluate reliability in
      extensive conditions.

PMID- 29367174
TI  - Dental age assessment: Which is the most applicable method?
AB  - To evaluate which method is the most applicable for estimating estimate dental
      age in Brazilian children, Nolla or Demirjian. For this purpose, both methods
      were reviewed and the differences between them brought to light. A total of 403
      healthy children between the ages of 7 and 13 years with satisfactory panoramic
      radiographs, similar socio-economic background and ethnic origin were included.
      Panoramic radiographs were examined by the Nolla and Demirjian methods. Dental
      age was calculated for both methods, and the differences between the dental age
      and the chronological age were compared with analysis of variance with post hoc
      Dunnett. The Nolla method showed no significant difference in relation to
      chronological age in the majority of age groups for boys and girls, except for 12
      year-old boys (over-estimation of 1.00) and between 11- and 12-year-old girls
      (over-estimation of 0.51 and 0.59, respectively). An over-estimation of the
      dental age was observed by using the Demirjian method (for boys 0.89-1.84 and for
      girls 0.69-1.97) for all age groups. The Nolla method is suitable for Brazilian
      children when it comes to age estimate with care to growth spurt beginning
      (around 11 and 12 years). However, the Dermijian method should not be used,
      because it over-estimated the age in both sexes.

PMID- 29367175
TI  - Modeling the multi-scale mechanisms of macromolecular resource allocation.
AB  - As microbes face changing environments, they dynamically allocate macromolecular
      resources to produce a particular phenotypic state. Broad 'omics' data sets have
      revealed several interesting phenomena regarding how the proteome is allocated
      under differing conditions, but the functional consequences of these states and
      how they are achieved remain open questions. Various types of multi-scale
      mathematical models have been used to elucidate the genetic basis for systems
      level adaptations. In this review, we outline several different strategies by
      which microbes accomplish resource allocation and detail how mathematical models
      have aided in our understanding of these processes. Ultimately, such modeling
      efforts have helped elucidate the principles of proteome allocation and hold
      promise for further discovery.

PMID- 29367176
TI  - The morphological changes and molecular biomarker responses in the liver of
      fluoride-exposed Bufo gargarizans larvae.
AB  - The goal of the current study was to evaluate the negative influences of fluoride
      on liver of Bufo gargarizans larvae. B. gargarizans larvae were treated with
      42.4mgF-/L for 0, 24, 48 and 72h at Gosner stage 37. The morphological changes
      and responses of molecular biomarkers involved in lipid metabolism, oxidative
      stress and apoptosis were examined in liver. Disappearance of cell boundaries,
      degeneration of hepatic parenchyma cells and significant increase in the number
      of melanomacrophage centres and the quantity of lipid droplets were found in the
      liver treated with 42.4mgF-/L for 72h. In addition, in the relative expression of
      acetyl CoA carboxylase 1 (ACC-1), fatty acid elongase 1 (FAE-1), sterol carrier
      protein 2 (SCP-2), and carnitine palmitoyltransferase-1 (CPT-1), decrease was
      observed after 24, 48 and 72h of 42.4mgF-/L exposure. Furthermore, the transcript
      levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were
      downregulated in tadpoles exposed for 24, 48 and 72h to 42.4mgF-/L, while the
      transcript level of heat shock protein 90 (HSP90) was upregulated at 42.4mgF-/L
      for 72h. Also, mRNA expression of Bcl-2-associated transcription factor 1(BCLAF1)
      and thyroid hormone receptors (TRalpha and TRbeta) was significantly upregulated
      in tadpoles treated with 42.4mgF-/L for 72h. Therefore, our results suggested
      that the liver injury induced by fluoride might result from disruption of lipid
      metabolism, oxidative damage and apoptosis.

PMID- 29367177
TI  - Association between fetal exposure to phthalate endocrine disruptor and genome
      wide DNA methylation at birth.
AB  - BACKGROUND: Phthalic acid esters are ubiquitous and antiandrogenic, and may cause
      systemic effects in humans, particularly with in utero exposure. Epigenetic
      modification, such as DNA methylation, has been hypothesized to be an important
      mechanism that mediates certain biological processes and pathogenic effects of in
      utero phthalate exposure. OBJECTIVE: The aim of this study was to examine the
      association between genome-wide DNA methylation at birth and prenatal exposure to
      phthalate. METHODS: We studied 64 infant-mother pairs included in TMICS (Taiwan
      Maternal and Infant Cohort Study), a long-term follow-up birth cohort from the
      general population. DNA methylation levels at more than 450,000 CpG sites were
      measured in cord blood samples using Illumina Infinium HumanMethylation450
      BeadChips. The concentrations of three metabolites of di-(2-ethylhexyl) phthalate
      (DEHP) were measured using liquid chromatography tandem-mass spectrometry (LC
      MS/MS) in urine samples collected from the pregnant women during 28-36 weeks
      gestation. RESULTS: We identified 25 CpG sites whose methylation levels in cord
      blood were significantly correlated with prenatal DEHP exposure using a false
      discovery rate (FDR) of 5% (q-value < 0.05). Via gene-set enrichment analysis
      (GSEA), we also found that there was significant enrichment of genes involved in
      the androgen response, estrogen response, and spermatogenesis within those genes
      showing DNA methylation changes in response to exposure. Specifically, PA2G4,
      HMGCR, and XRCC6 genes were involved in genes in response to androgen.
      CONCLUSIONS: Phthalate exposure in utero may cause significant alterations in the
      DNA methylation in cord blood. These changes in DNA methylation might serve as
      biomarkers of maternal exposure to phthalate in infancy and potential candidates
      for studying mechanisms via which phthalate may impact on health in later life.
      Future investigations are warranted.

PMID- 29367178
TI  - Ictal and interictal MEG in pediatric patients with tuberous sclerosis and drug
      resistant epilepsy.
AB  - PURPOSE: Drug resistant epilepsy (DRE) is common in patients with tuberous
      sclerosis (TS). Interictal MEG has been shown as a valuable instrument in the
      presurgical workup. The goal of our study was to evaluate the role of ictal MEG
      in epileptogenic tuber selection, especially in patients with multiple irritative
      zones. METHODS: The clinical and MEG data of 23 patients with TS and DRE from two
      medical/research centers were reviewed. Seven pediatric patients, who had
      seizures during MEG recording and underwent resection or disconnection surgery,
      were included into the study. Cortical sources of ictal and interictal
      epileptiform MEG discharges were compared with epileptogenic zone location in six
      patients with favorable surgery outcome. RESULTS: In patients who improved
      substantially after surgery all resected and several other tubers demonstrated
      epileptiform activity on interictal MEG. Ictal MEG provided crucial information
      about lobar location of the seizure onset zone (SOZ) in two cases, and in the
      other four it confirmed the SOZ location derived from the interictal data. In one
      case, ictal MEG findings were unreliable. In one patient, who did not benefit
      from surgical treatment, the resected tubers did not overlap with interictal and
      ictal MEG sources. CONCLUSION: The combination of interictal and ictal MEG is a
      valuable tool for identification of the epileptogenic tuber/tubers in presurgical
      work-up in patients with TS.

PMID- 29367179
TI  - Childhood-onset generalized epilepsy in Bainbridge-Ropers syndrome.
AB  - Bainbridge-Ropers syndrome is a genetic syndrome caused by heterozygous loss-of
      function pathogenic variants in ASXL3, which encodes a protein involved in
      transcriptional regulation. Affected individuals have multiple abnormalities
      including developmental impairment, hypotonia and characteristic facial features.
      Seizures are reported in approximately a third of cases; however, the
      epileptology has not been thoroughly studied. We identified three patients with
      pathogenic ASXL3 variants and seizures at Austin Health and in the DECIPHER
      database. These three patients had novel de novo ASXL3 pathogenic variants, two
      with truncation variants and one with a splice site variant. All three had
      childhood-onset generalized epilepsy with generalized tonic-clonic seizures, with
      one also having atypical absence seizures. We also reviewed available clinical
      data on five published patients with Bainbridge-Ropers syndrome and seizures. Of
      the five previously published patients, three also had generalized tonic-clonic
      seizures, one of whom also had possible absence seizures; a fourth patient had
      absence seizures and possible focal seizures. EEG typically showed features
      consistent with generalized epilepsy including generalized spike-wave,
      photoparoxysmal response, and occipital intermittent rhythmic epileptiform
      activity. Bainbridge-Ropers syndrome is associated with childhood-onset
      generalized epilepsy with generalized tonic-clonic seizures and/or atypical
      absence seizures.

PMID- 29367180
TI  - Fosphenytoin pre-medication for pediatric extra-operative electrical stimulation
      brain mapping.
AB  - PURPOSE: We studied the effect of fosphenytoin (FOS) pre-medication on the
      incidence and thresholds of after-discharges (ADs), seizures, and functional
      responses during electrical stimulation mapping (ESM). METHODS: As individualized
      by the attending epileptologist, FOS was given intravenously at 2 mg-phenytoin
      equivalents (PE)/kg/min or 150 mg-PE/min (whichever slower). Patients who
      received and did not receive FOS were compared for the incidence and thresholds
      of ADs, seizures, and functional responses. RESULTS: Before ESM, 40 and 82
      patients respectively were pre-medicated/not pre-medicated with FOS. The
      incidence of ESM-induced seizures was significantly lower in FOS pre-medicated
      patients (22.5% vs. 42.7%, p = 0.044), whereas temporal language threshold was
      higher (9.2 vs. 6.5 mA, p = 0.032). FOS was more efficacious in preventing ESM
      induced seizures in patients with symptomatogenic zone ipsilateral to the side of
      ESM. Although FOS dose had no significant effect on minimum language, minimum
      motor, or AD thresholds; seizure and temporal language thresholds showed trends
      approaching significance, intersecting at 12.2 mg-PE/kg. The incidence of ESM
      induced seizures was significantly lower in those who received FOS at a dose of
      <=12 mg/kg (9.1%) compared to those who did not receive any FOS (42.7%, p =
      0.046), while the temporal language thresholds were not significantly different
      (6.3 vs. 6.5 mA, p = 0.897). CONCLUSIONS: This study provides class III evidence
      that FOS pre-medication before ESM decreases the incidence of ESM-induced
      seizures, but increases temporal language threshold. FOS pre-medication may thus
      be considered before ESM. Future studies should prospectively verify these
      observations and characterize dose-response relationships.

PMID- 29367181
TI  - The Use of Online Health Forums by Patients With Chronic Cough: Qualitative
      Study.
AB  - BACKGROUND: Online health discussion forums are used by different patient groups
      for sharing advice and information. Chronic cough is a common problem, and people
      with chronic cough use online health forums alongside formal medical therapies.
      OBJECTIVE: The objective of this study was to assess how chronic cough sufferers
      use online health forums, including the treatment advice they share with one
      another and the possible clinical uses of online forums in chronic cough.
      METHODS: Three open-access health forums were searched for threads related to
      chronic cough. Identified threads were screened against inclusion and exclusion
      criteria adapted from the British Thoracic Society (BTS) Guidelines related to
      chronic cough diagnosis. Included data were subjected to qualitative thematic
      analysis. All study data were cross-validated by a second author and
      discrepancies were resolved. RESULTS: In total, 96 threads were included in the
      analysis, consisting of posts by 223 forum users. Three main themes were
      identified: the effect of chronic cough on the lives of patients, the treatment
      advice shared between users, and the provision of support within forums.
      CONCLUSIONS: Chronic cough symptoms had impacts on multiple aspects of patients'
      health and well-being. To try and combat these issues, forum users suggested a
      variety of treatments to one another, ranging from mainstream traditional
      therapies to odd alternative remedies. The provision of support and empathy were
      also prominent themes in discussion threads. Online forums themselves may provide
      increasing benefit to users through the addition of a moderator.

PMID- 29367182
TI  - Gender Differences in and the Relationships Between Social Anxiety and
      Problematic Internet Use: Canonical Analysis.
AB  - BACKGROUND: The cognitive-behavioral model of problematic Internet use (PIU)
      proposes that psychological well-being is associated with specific thoughts and
      behaviors on the Internet. Hence, there is growing concern that PIU is associated
      with psychological impairments. OBJECTIVE: Given the proposal of gender schema
      theory and social role theory, men and women are predisposed to experience social
      anxiety and engage in Internet use differently. Thus, an investigation of gender
      differences in these areas is warranted. According to the cognitive-behavioral
      model of PIU, social anxiety is associated with specific cognitions and behaviors
      on the Internet. Thus, an investigation of the association between social anxiety
      and PIU is essential. In addition, research that takes into account the
      multidimensional nature of social anxiety and PIU is lacking. Therefore, this
      study aimed to explore multivariate gender differences in and the relationships
      between social anxiety and PIU. METHODS: Participants included 505 college
      students, of whom 241 (47.7%) were women and 264 (52.3%) were men. Participants'
      ages ranged from 18 to 22 years, with a mean age of 20.34 (SD=1.16). The Social
      Anxiety Scale and Problematic Internet Use Scale were used in data collection.
      Multivariate analysis of variance (MANOVA) and canonical correlation analysis
      were used. RESULTS: Mean differences between men and women were not statistically
      significant in social anxiety (lambda=.02, F3,501=2.47, P=.06). In all three PIU
      dimensions, men scored higher than women, and MANOVA shows that multivariate
      difference was statistically significant (lambda=.94, F3,501=10.69, P<.001). Of
      the canonical correlation functions computed for men, only the first was
      significant (Rc=.43, lambda=.78, chi29=64.7, P<.001) and accounted for 19% of the
      overlapping variance. Similarly, only the first canonical function was
      significant for women (Rc=.36, lambda=.87, chi29=33.9, P<.001), which accounted
      for 13% of the overlapping variance. CONCLUSIONS: On the basis of the findings,
      we conclude that enhanced educational opportunities for women and their
      increasing role in the society have led women to become more active and thus
      closed the gap in social anxiety levels between men and women. We found that men
      showed more difficulties than women in terms of running away from personal
      problems (ie, social benefit), used the Internet more excessively, and
      experienced more interpersonal problems with significant others due to Internet
      use. We conclude that men are under a greater risk of social impairments due to
      PIU. Our overall conclusion is that there is a substantial amount of association
      between social anxiety and PIU and the association is stronger for men than it is
      for women. We advise that future research continue to investigate PIU and social
      anxiety as multidimensional constructs.

PMID- 29367183
TI  - Facilitating Factors and Barriers to the Use of Emerging Technologies for Suicide
      Prevention in Europe: Multicountry Exploratory Study.
AB  - BACKGROUND: This study provides an analysis on the use of emerging technologies
      for the prevention of suicide in 8 different European countries. OBJECTIVE: The
      objective of this study was to analyze the potentiality of using emerging
      technologies in the area of suicide prevention based on the opinion of different
      professionals involved in suicide prevention. METHODS: Opinions of 3 groups of
      stakeholders (ie, relevant professionals in suicide field) were gathered using a
      specifically designed questionnaire to explore dimensions underlying perceptions
      of facilitating factors and barriers in relation to the use of emerging
      technologies for suicide prevention. RESULTS: Goal 1 involved facilitating
      factors for the use of emerging technologies in suicide prevention. Northern
      European countries, except for Belgium, attach greater relevance to those that
      optimize implementation and benefits. On the other hand, Southern European
      countries attach greater importance to professionally oriented and user-centered
      facilitating factors. According to different stakeholders, the analysis of these
      facilitating factors suggest that professionals in the field of social work
      attach greater relevance to those that optimize implementation and benefits.
      However, professionals involved in the area of mental health, policy makers, and
      political decision makers give greater importance to professionally oriented and
      user-centered facilitating factors. Goal 2 was related to barriers to the
      usability of emerging technologies for suicide prevention. Both countries and
      stakeholders attach greater importance to barriers associated with resource
      constraints than to those centered on personal limitations. There are no
      differences between countries or between stakeholders. Nevertheless, there is a
      certain stakeholders-countries interaction that indicates that the opinions on
      resource constraints expressed by different stakeholders do not follow a uniform
      pattern in different countries, but they differ depending on the country.
      CONCLUSIONS: Although all countries and stakeholders agree in identifying
      resource constraints as the main barrier to the use of emerging technologies,
      factors facilitating their use in suicide prevention differ among countries and
      among stakeholders.

PMID- 29367184
TI  - Activating Technology for Connected Health in Cancer: Protocol for a Research and
      Training Program.
AB  - BACKGROUND: As cancer survival rates increase, the challenge of ensuring that
      cancer survivors reclaim their quality of life (QoL) becomes more important. This
      paper outlines the research element of a research and training program that is
      designed to do just that. OBJECTIVE: Bridging sectors, disciplines, and
      geographies, it brings together eight PhD projects and students from across
      Europe to identify the underlying barriers, test different technology-enabled
      rehabilitative approaches, propose a model to optimize the patient pathways, and
      examine the business models that might underpin a sustainable approach to cancer
      survivor reintegration using technology. METHODS: The program, funded under the
      European Union's Horizon 2020 research and innovation program under the Marie
      Sklodowska-Curie grant agreement No 722012, includes deep disciplinary PhD
      projects, intersectoral and international secondments, interdisciplinary plenary
      training schools, and virtual subject-specific education modules. RESULTS: The 8
      students have now been recruited and are at the early stages of their projects.
      CONCLUSIONS: CATCH will provide a comprehensive training and research program by
      embracing all key elements-technical, social, and economic sciences-required to
      produce researchers and project outcomes that are capable of meeting existing and
      future needs in cancer rehabilitation.

PMID- 29367186
TI  - The Use of Facebook Advertising to Recruit Healthy Elderly People for a Clinical
      Trial: Baseline Metrics.
AB  - BACKGROUND: This report provides data on the use of social media advertising as a
      clinical trial recruitment strategy targeting healthy volunteers aged 60 years
      and older. The social media advertising campaign focused on enrollment for a
      Phase 1 clinical trial. Traditional means of recruiting-billboards, newspaper
      advertising, word of mouth, personal referrals, and direct mail-were not
      producing enough qualified participants. OBJECTIVE: To demonstrate the
      effectiveness of using targeted advertising on the social networking site
      Facebook to recruit people aged 60 years and older for volunteer clinical trial
      participation. METHODS: The trial sponsor used a proactive approach to recruit
      participants using advertising on social media. The sponsor placed and monitored
      an Institutional Review Board-approved advertising campaign on Facebook to
      recruit potential candidates for a Phase 1 clinical trial. The clinical trial
      required a 10-day residential (overnight) stay at a clinic in Michigan, with one
      follow-up visit. The sponsor of the clinical trial placed the advertising, which
      directed interested respondents to a trial-specific landing page controlled by
      the Contract Research Organization (CRO). The CRO provided all follow-up
      consenting, prescreening, screening, and enrollment procedures. The campaign was
      waged over an 8-week period to supplement recruiting by the CRO. RESULTS: A total
      of 621 people responded to a Facebook advertising campaign by completing an
      online form or telephoning the CRO, and the clinical trial was fully enrolled at
      45 subjects following an 8-week Facebook advertising campaign. CONCLUSIONS: An 8
      week Facebook advertising campaign contributed to 868 inquiries made regarding a
      Phase 1 clinical trial seeking to enroll healthy elderly subjects. Over the
      initial 11 weeks of recruitment, 178 inquiries were received using traditional
      methods of outreach. Respondents to the Facebook advertising campaign described
      in this report engaged with the sponsored advertising at a higher rate than is
      typical for social media-based clinical trial recruitment strategies. The older
      adults' engagement rate of 4.92% was more than twice as high as click-through
      rates of younger adults engaged with social media advertising in other clinical
      trial recruitment studies. Advertising placed on the social media platform
      Facebook is effective with the healthy volunteer population aged 60 years and
      older. This approach can quickly and cost-effectively reach qualified candidates
      for clinical trial recruitment as a supplement to traditional means of
      recruiting. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02840279;
      https://clinicaltrials.gov/ct2/show/NCT02840279 (Archived by WebCite at
      http://www.webcitation.org/6wamIWXAt).

PMID- 29367185
TI  - Effect of Contract Compliance Rate to a Fourth-Generation Telehealth Program on
      the Risk of Hospitalization in Patients With Chronic Kidney Disease:
      Retrospective Cohort Study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is prevalent in Taiwan and it is
      associated with high all-cause mortality. We have shown in a previous paper that
      a fourth-generation telehealth program is associated with lower all-cause
      mortality compared to usual care with a hazard ratio of 0.866 (95% CI 0.837
      0.896). OBJECTIVE: This study aimed to evaluate the effect of renal function
      status on hospitalization among patients receiving this program and to evaluate
      the relationship between contract compliance rate to the program and risk of
      hospitalization in patients with CKD. METHODS: We retrospectively analyzed 715
      patients receiving the telehealth care program. Contract compliance rate was
      defined as the percentage of days covered by the telehealth service before
      hospitalization. Patients were stratified into three groups according to renal
      function status: (1) normal renal function, (2) CKD, or (3) end-stage renal
      disease (ESRD) and on maintenance dialysis. The outcome measurements were first
      cardiovascular and all-cause hospitalizations. The association between contract
      compliance rate, renal function status, and hospitalization risk was analyzed
      with a Cox proportional hazards model with time-dependent covariates. RESULTS:
      The median follow-up duration was 694 days (IQR 338-1163). Contract compliance
      rate had a triphasic relationship with cardiovascular and all-cause
      hospitalizations. Patients with low or very high contract compliance rates were
      associated with a higher risk of hospitalization. Patients with CKD or ESRD were
      also associated with a higher risk of hospitalization. Moreover, we observed a
      significant interaction between the effects of renal function status and contract
      compliance rate on the risk of hospitalization: patients with ESRD, who were on
      dialysis, had an increased risk of hospitalization at a lower contract compliance
      rate, compared with patients with normal renal function or CKD. CONCLUSIONS: Our
      study showed that there was a triphasic relationship between contract compliance
      rate to the telehealth program and risk of hospitalization. Renal function status
      was associated with risk of hospitalization among these patients, and there was a
      significant interaction with contract compliance rate.

PMID- 29367188
TI  - Chronobiology --2017 Nobel Prize in Physiology or Medicine.
AB  - Chronobiology is a field of biology that examines the generation of biological
      rhythms in various creatures and in many parts of body, and their adaptive
      fitness to solar- and lunar-related periodic phenomena. The synchronization of
      internal circadian clocks with external timing signals confers accurate phase
      response and tissue homeostasis. Herein we state a series of studies on circadian
      rhythms and introduce the brief history of chronobiology. We also present a
      detailed timeline of the discoveries on molecular mechanisms controlling
      circadian rhythm in Drosophila, which was awarded the 2017 Nobel Prize in
      Physiology or Medicine. The latest findings and new perspectives are further
      summarized to indicate the significance of circadian research.

PMID- 29367187
TI  - Quality of Decision Support in Computerized Provider Order Entry: Systematic
      Literature Review.
AB  - BACKGROUND: Computerized decision support systems have raised a lot of hopes and
      expectations in the field of order entry. Although there are numerous studies
      reporting positive impacts, concerns are increasingly high about alert fatigue
      and effective impacts of these systems. One of the root causes of fatigue alert
      reported is the low clinical relevance of these alerts. OBJECTIVE: The objective
      of this systematic review was to assess the reported positive predictive value
      (PPV), as a proxy to clinical relevance, of decision support systems in
      computerized provider order entry (CPOE). METHODS: A systematic search of the
      scientific literature published between February 2009 and March 2015 on CPOE,
      clinical decision support systems, and the predictive value associated with alert
      fatigue was conducted using PubMed database. Inclusion criteria were as follows:
      English language, full text available (free or pay for access), assessed
      medication, direct or indirect level of predictive value, sensitivity, or
      specificity. When possible with the information provided, PPV was calculated or
      evaluated. RESULTS: Additive queries on PubMed retrieved 928 candidate papers. Of
      these, 376 were eligible based on abstract. Finally, 26 studies qualified for a
      full-text review, and 17 provided enough information for the study objectives. An
      additional 4 papers were added from the references of the reviewed papers. The
      results demonstrate massive variations in PPVs ranging from 8% to 83% according
      to the object of the decision support, with most results between 20% and 40%. The
      best results were observed when patients' characteristics, such as comorbidity or
      laboratory test results, were taken into account. There was also an important
      variation in sensitivity, ranging from 38% to 91%. CONCLUSIONS: There is
      increasing reporting of alerts override in CPOE decision support. Several causes
      are discussed in the literature, the most important one being the clinical
      relevance of alerts. In this paper, we tried to assess formally the clinical
      relevance of alerts, using a near-strong proxy, which is the PPV of alerts, or
      any way to express it such as the rate of true and false positive alerts. In
      doing this literature review, three inferences were drawn. First, very few papers
      report direct or enough indirect elements that support the use or the computation
      of PPV, which is a gold standard for all diagnostic tools in medicine and should
      be systematically reported for decision support. Second, the PPV varies a lot
      according to the typology of decision support, so that overall rates are not
      useful, but must be reported by the type of alert. Finally, in general, the PPVs
      are below or near 50%, which can be considered as very low.

PMID- 29367189
TI  - The critical roles of TBC proteins in human diseases.
AB  - The Tre-2/Bub2/Cdc16 (TBC) domain is a conserved protein motif consisting of
      approximately 200 amino acids, and is present in many eukaryotic proteins. TBC
      domain-containing proteins (TBC proteins) function as GTPase activating proteins
      (GAPs) for the small GTPase Rab, which can promote the hydrolysis of Rab-GTP to
      Rab-GDP in regulation of specific intracellular trafficking pathways. Several TBC
      proteins play important roles in cellular functions in mammals, and defects of
      which are closely associated with numerous disease processes. In this review, we
      summarize the structures and functions of the mammalian TBC proteins and recent
      advances in understanding their critical roles in the development of human
      diseases. This review serves as a reference for further investigations on the
      functions of TBC proteins in disease pathogeneses.

PMID- 29367190
TI  - Progress of GATA6 in liver development.
AB  - GATA binding protein 6 (GATA6) is a member of the GATA family of zinc-finger
      transcriptional regulators, whose names come from the conservative base sequence
      (G/A)GATA(A/T). The GATA families play key roles in cell fate determination,
      proliferation, migration, and organogenesis of endoderm- and mesoderm-derived
      organs in vertebrates. As a lineage-specific factor, a chromatin remodeling
      factor, a pluripotent factor and a pioneer factor, GATA6 is involved in various
      stages of liver development, including endoderm liver-lineage determination,
      liver specification, hepatic bud outgrowth and hepatoblast differentiation. In
      this review, we summarize recent progress in the roles and regulatory mechanisms
      of GATA6 in liver development.

PMID- 29367191
TI  - Progress in ZIP transporter gene family in rice.
AB  - Zinc and iron are essential mineral elements for the growth of Oryza sativa L.
      and also micronutrients for human health. Therefore, it is vital to study
      biofortification of rice with Zn and Fe in order to improve the yield and quality
      of rice, as well as to enhance nutritional states of humans. The zinc-regulated
      transporters and iron-regulated transporter-like proteins (the ZIP family)
      control the absorption and translocation of Zn and Fe and maintain their
      homeostasis in rice. Reciprocally, the expression of the ZIP family is induced by
      the concentration of Zn and Fe. There are abundant natural allelic variations of
      the ZIP genes, and some haplotypes only occur in indica or japonica, which could
      affect Zn and Fe accumulation levels between these subspecies. Currently,
      emerging functional studies of the accumulation mechanism of Zn and Fe in grains
      reveal that a lot still needs to be learned about the allele variations of ZIP
      genes. In fact, only OsZIP3 is functional characterized. In this review, we
      summarize the latest progress in the molecular characteristics of the ZIP
      transporters, including protein localization, gene expression patterns, transport
      mechanism, metal ion interaction, and natural allelic variations.

PMID- 29367192
TI  - Progress in plant paleogenomics.
AB  - As a new branch of genomics, plant paleogenomics reconstructs ancestral genomes
      from actual modern species and infers palaeohistory, evolutionary and/or
      speciation events that have shaped the modern species. Advances in high
      throughput sequencing technologies yield accurate long reads, promote the
      progress of plant genome sequence assembly, and thereby offer paleogenomics a
      large collection of valuable reference genomes from modern species. Whole-genome
      duplication (WGD) and polyploidization cause rapid genomic reorganization,
      massive gene losses and structural variations. WGD events are therefore central
      to plant evolution. In this review, we summarize recent progress in sequencing
      and assembly of plant genomes, principles of plant paleogenomics, WGD events in
      plant genomes, and the most likely evolutionary scenario in plants. Furthermore,
      we highlight some of the challenges as well as future directions.

PMID- 29367193
TI  - Bacterial genome-wide association study: methodologies and applications.
AB  - With the development of genome sequencing and the accumulation of whole genome
      sequences, genome-wide association study (GWAS) has achieved remarkable advances
      in understanding of human complex disease, and tens of thousands of disease risk
      factors have been found. Meanwhile, GWAS provides a new tool for exploring the
      genetic mechanism of bacterial phenotypes. Since the publication of the first
      bacterial GWAS (BGWAS) work in 2013, there have been more than 10 reports, which
      reveal the genetic basis of host adaption, drug resistance and virulence, etc.
      These findings greatly enhance our understanding on genetics, evolution and
      spread of bacteria. In this review, we summarize the current methodologies,
      applications and problems of BGWAS and highlight its potential in future
      research, which aims to provide helps for the applications of BGWAS in the field
      of microbiology.

PMID- 29367194
TI  - Construction of FGF21 knockout mouse models by the CRISPR/Cas9 system.
AB  - Fibroblast growth factors (FGFs) are multifunctional signal molecules between
      cells, regulating the various physiological functions of the organism. FGF21 is a
      regulatory factor of the FGF family and has been postulated to play important
      roles in hair follicle development and hair follicle growth cycle. To evaluate
      the roles of FGF21, we had established a FGF21 knockout mouse model, using the
      CRISPR/Cas9 technology. We had constructed a FGF21 targeting vector and
      microinjected it with Cas9 mRNA and gRNA into fertilized ova of FVB mice. The
      gRNA was designed to target the exon 1 of the endogenous mouse FGF21 gene. Three
      lines of Fgf21 -/- mice were obtained from these experiments, and confirmed to
      harbor Fgf21 -/- genotypes and null expression phenotype, using DNA sequencing,
      qRT-PCR and Western blotting. FGF21 mRNA and FGF21 protein were not detected in
      tissues of these Fgf21 -/- mice. Depilation and histochemistry analyses showed
      that the Fgf21 -/- mice had lower body weight, slower hair regrowth and poorer
      hair quantities and smaller hair follicles diameters, as compared to WT mice. The
      Fgf21 -/- mice reported here could provide a useful genetic model for future
      studies of FGF21 functions in hair follicle development and hair follicle growth
      cycle.

PMID- 29367195
TI  - Application of medical cases in general genetics teaching in universities.
AB  - General genetics is a core course in life sciences, medicine, agriculture and
      other related fields. As one of the most fast-developing disciplines of life
      sciences in the 21th century, the influence of the genetics knowledge on daily
      life is expanding, especially on human health and reproduction. In order to make
      it easier for students to understand the profound principles of genetics and to
      better apply the theories to daily life, we have introduced appropriate medical
      cases in general genetics teaching and further extended them combined with
      theoretical basis of genetics. This approach will be beneficial to enhance
      students' abilities of genetic analysis and promote their enthusiasm to learn and
      master practical skills. In this paper, we enumerate medical cases related to the
      modern genetics teaching system to provide a reference for genetics teaching in
      general and normal universities.

PMID- 29367196
TI  - Chromatin-Remodeling Genes Promote Immunotherapy Resistance.
AB  - Two studies show that genes that encode a chromatin-remodeling complex foster
      resistance to checkpoint inhibitors. One study identified the proteins by using
      CRISPR/Cas9 to knock out genes in mouse melanoma cells. The other study converged
      on the same result by identifying mutations in patients with clear cell renal
      cell carcinoma who responded to PD-1 inhibitors.

PMID- 29367197
TI  - Circulating Tumor DNA Genomics Correlate with Resistance to Abiraterone and
      Enzalutamide in Prostate Cancer.
AB  - Primary resistance to androgen receptor (AR)-directed therapies in metastatic
      castration-resistant prostate cancer (mCRPC) is poorly understood. We randomized
      202 patients with treatment-naive mCRPC to abiraterone or enzalutamide and
      performed whole-exome and deep targeted 72-gene sequencing of plasma cell-free
      DNA prior to therapy. For these agents, which have never been directly compared,
      time to progression was similar. Defects in BRCA2 and ATM were strongly
      associated with poor clinical outcomes independently of clinical prognostic
      factors and circulating tumor DNA abundance. Somatic alterations in TP53,
      previously linked to reduced tumor dependency on AR signaling, were also
      independently associated with rapid resistance. Although detection of AR
      amplifications did not outperform standard prognostic biomarkers, AR gene
      structural rearrangements truncating the ligand binding domain were identified in
      several patients with primary resistance. These findings establish genomic
      drivers of resistance to first-line AR-directed therapy in mCRPC and identify
      potential minimally invasive biomarkers.Significance: Leveraging plasma specimens
      collected in a large randomized phase II trial, we report the relative impact of
      common circulating tumor DNA alterations on patient response to the most widely
      used therapies for advanced prostate cancer. Our findings suggest that liquid
      biopsy analysis can guide the use of AR-targeted therapy in general practice.
      Cancer Discov; 8(4); 444-57. (c)2018 AACR.See related commentary by Jayaram et
      al., p. 392This article is highlighted in the In This Issue feature, p. 371.

PMID- 29367199
TI  - Looking in the rear-view mirror as we anticipate another 100 years.

PMID- 29367198
TI  - Preoperative physiotherapy for the prevention of respiratory complications after
      upper abdominal surgery: pragmatic, double blinded, multicentre randomised
      controlled trial.
AB  - OBJECTIVE: To assess the efficacy of a single preoperative physiotherapy session
      to reduce postoperative pulmonary complications (PPCs) after upper abdominal
      surgery. DESIGN: Prospective, pragmatic, multicentre, patient and assessor
      blinded, parallel group, randomised placebo controlled superiority trial.
      SETTING: Multidisciplinary preadmission clinics at three tertiary public
      hospitals in Australia and New Zealand. PARTICIPANTS: 441 adults aged 18 years or
      older who were within six weeks of elective major open upper abdominal surgery
      were randomly assigned through concealed allocation to receive either an
      information booklet (n=219; control) or preoperative physiotherapy (n=222;
      intervention) and followed for 12 months. 432 completed the trial. INTERVENTIONS:
      Preoperatively, participants received an information booklet (control) or an
      additional 30 minute physiotherapy education and breathing exercise training
      session (intervention). Education focused on PPCs and their prevention through
      early ambulation and self directed breathing exercises to be initiated
      immediately on regaining consciousness after surgery. Postoperatively, all
      participants received standardised early ambulation, and no additional
      respiratory physiotherapy was provided. MAIN OUTCOME MEASURES: The primary
      outcome was a PPC within 14 postoperative hospital days assessed daily using the
      Melbourne group score. Secondary outcomes were hospital acquired pneumonia,
      length of hospital stay, utilisation of intensive care unit services, and
      hospital costs. Patient reported health related quality of life, physical
      function, and post-discharge complications were measured at six weeks, and all
      cause mortality was measured to 12 months. RESULTS: The incidence of PPCs within
      14 postoperative hospital days, including hospital acquired pneumonia, was halved
      (adjusted hazard ratio 0.48, 95% confidence interval 0.30 to 0.75, P=0.001) in
      the intervention group compared with the control group, with an absolute risk
      reduction of 15% (95% confidence interval 7% to 22%) and a number needed to treat
      of 7 (95% confidence interval 5 to 14). No significant differences in other
      secondary outcomes were detected. CONCLUSION: In a general population of patients
      listed for elective upper abdominal surgery, a 30 minute preoperative
      physiotherapy session provided within existing hospital multidisciplinary
      preadmission clinics halves the incidence of PPCs and specifically hospital
      acquired pneumonia. Further research is required to investigate benefits to
      mortality and length of stay. TRIAL REGISTRATION: Australian New Zealand Clinical
      Trials Registry ANZCTR 12613000664741.

PMID- 29367200
TI  - Novel mutation in the choroideremia gene and multi-Mendelian phenotypes in
      Spanish families.
AB  - AIMS: We aimed to accurately diagnose several retinitis pigmentosa (RP) patients
      with complex ocular phenotypes by combining massive sequencing genetic diagnosis
      and powerful clinical imaging techniques. METHODS: Whole-exome sequencing (WES)
      of selected patients from two RP families was undertaken. The variants identified
      were validated by Sanger sequencing and cosegregation analysis. Accurate clinical
      re-evaluation was performed using electrophysiological and visual field records
      as well as non-invasive imaging techniques, such as swept-source optical
      coherence tomography and fundus autofluorescence. RESULTS: The WES results
      highlighted one novel and one reported causative mutations in the X-linked
      choroideremia gene (CHM), which challenged the initial RP diagnosis. Subsequent
      clinical re-evaluation confirmed the choroideremia diagnosis. Carrier females
      showed different degrees of affectation, even between twin sisters, probably due
      to lyonization. A severe multi-Mendelian phenotype was associated with
      coincidental dominant pathogenic mutations in two additional genes: PAX6 and
      PDE6B. CONCLUSIONS: Genetic diagnosis via massive sequencing is instrumental in
      identifying causative mutations in retinal dystrophies and additional genetic
      variants with an impact on the phenotype. Multi-Mendelian phenotypes previously
      ascribed to rare syndromes can thus be dissected and molecularly diagnosed.
      Overall, the combination of powerful genetic diagnosis and clinical non-invasive
      imaging techniques enables efficient management of patients and their
      prioritisation for gene-specific therapies.

PMID- 29367201
TI  - Corneal staining patterns in vernal keratoconjunctivitis: the new VKC-CLEK
      scoring scale.
AB  - AIM: To propose a new scoring system in the assessment of ocular surface
      epithelial damage in vernal keratoconjunctivitis (VKC). METHODS: 25 consecutive
      patients with VKC (50 eyes) were evaluated using the Quality of Life in children
      with VKC (QUICK) questionnaire and objective clinical measures: fluorescein and
      lissamine green staining and cornea confocal microscopy (Heidelberg Retina
      Tomography 3). Oxford, Van Bljsterweld and a new system, the VKC-Collaborative
      Longitudinal Evaluation of Keratoconus study (CLEK) (VKC-CLEK) scores, were used
      to evaluate the epithelial damage after staining. RESULTS: Mean Oxford and VKC
      CLEK scores were significantly different after fluorescein staining (P<0.001),
      but significantly correlated (P<0.001; r=0.649). The same data were obtained
      comparing Van Bljsterweld and VKC-CLEK after lissamine green staining (P<0.001;
      r=0.760). In patient with limbal VKC, a statistically significant difference was
      found comparing new VKC-CLEK scores and Oxford or Van Bljsterweld scores
      (P<0.001), but not in tarsal VKC. A statistically superior concordance was found
      between QUICK and VKC-CLEK scores compared with standard staining scores values
      (P<0.001). CONCLUSIONS: Oxford and Van Bijsterveld scores are not adequate for
      the evaluation of the epithelial damage in patients with limbal VKC because the
      staining patterns considered for these tests do not correspond to the staining
      patterns in patients with VKC. We propose a new scoring system, VKC-CLEK, to
      better evaluate both limbal and tarsal epithelial damage in patients with VKC.

PMID- 29367202
TI  - Prevalence and incidence of presbyopia in urban Southern China.
AB  - AIMS: To investigate the prevalence and incidence of presbyopia in an urban
      Chinese population. METHODS: 1817 subjects aged >=35 years were identified by
      random cluster sampling in Yuexiu District, Guangzhou, China, at baseline in
      2008, and all were invited for the follow-up examination in 2014. Distance and
      near visual acuity (VA) tests, as well as non-cycloplegic automated refraction
      were performed at each examination as per standardised protocol. Participants
      with presenting near VA <=20/40 were further tested with add power at a standard
      distance of 40 cm to obtain their best-corrected near VA. Functional presbyopia
      was defined as near VA under presenting distance refraction correction of <20/50
      and could be improved by at least one line with add power. RESULTS: A total of
      1191 (83.5% of the 2014 follow-up) participants were included in the current
      analysis with a mean (SD) age of 50.4 (9.7) years, and 52.9% were female.
      Prevalence of functional presbyopia at baseline was 25.2% (95% CI 21.5 to 28.9)
      and the 6-year incidence was 42.8% (95% CI 39.4 to 50.1). Older and more
      hyperopic subjects had both higher prevalence and incidence of presbyopia
      (P<0.001). Average presbyopic correction coverage (PCC) was 87.7% at baseline and
      was significantly lower in myopic participants (P=0.006). CONCLUSIONS: Prevalence
      of functional presbyopia in urban China is relatively lower along with a higher
      PCC compared with previous population-based rural cohorts. We identified a high
      presbyopia incidence, and further studies are needed to understand longitudinal
      presbyopia progression as well as the urban-rural gap in presbyopia to throw
      light on future strategic planning.

PMID- 29367203
TI  - Implementation and Improvement of Pediatric Asthma Guideline Improves Hospital
      Based Care.
AB  - BACKGROUND: Standardized pediatric asthma care has been shown to improve measures
      in specific hospital areas, but to our knowledge, the implementation of an asthma
      clinical practice guideline (CPG) has not been demonstrated to be associated with
      improved hospital-wide outcomes. We sought to implement and refine a pediatric
      asthma CPG to improve outcomes and throughput for the emergency department (ED),
      inpatient care, and the ICU. METHODS: An urban, quaternary-care children's
      hospital developed and implemented an evidence-based, pediatric asthma CPG to
      standardize care from ED arrival through discharge for all primary diagnosis
      asthma encounters for patients >=2 years old without a complex chronic condition.
      Primary outcomes included ED and inpatient length of stay (LOS), percent ED
      encounters requiring admission, percent admissions requiring ICU care, and total
      charges. Balancing measures included the number of asthma discharges between all
      cause 30-day readmissions after asthma discharges and asthma relapse within 72
      hours. Statistical process control charts were used to monitor and analyze
      outcomes. RESULTS: Analyses included 3650 and 3467 encounters 2 years pre- and
      postimplementation, respectively. Postimplementation, reductions were seen in ED
      LOS for treat-and-release patients (3.9 hours vs 3.3 hours), hospital LOS (1.5
      days vs 1.3 days), ED encounters requiring admission (23.5% vs 18.8%), admissions
      requiring ICU (23.0% vs 13.2%), and total charges ($4457 vs $3651). Guideline
      implementation was not associated with changes in balancing measures.
      CONCLUSIONS: The hospital-wide standardization of a pediatric asthma CPG across
      hospital units can safely reduce overall hospital resource intensity by reducing
      LOS, admissions, ICU services, and charges.

PMID- 29367204
TI  - Cardiac Arrest Survival in Pediatric and General Emergency Departments.
AB  - BACKGROUND AND OBJECTIVES: Pediatric out-of-hospital cardiac arrest (OHCA) has a
      low rate of survival to hospital discharge. Understanding whether pediatric
      emergency departments (EDs) have higher survival than general EDs may help
      identify ways to improve care for all patients with OHCA. We sought to determine
      if OHCA survival differs between pediatric and general EDs. METHODS: We used the
      2009-2014 Nationwide Emergency Department Sample to study children under 18 with
      cardiac arrest. We compared pediatric EDs (those with >75% pediatric visits) to
      general EDs on the outcome of survival to hospital discharge or transfer. We
      determined unadjusted and adjusted survival, accounting for age, region, and
      injury severity. Analyses were stratified by nontraumatic versus traumatic cause.
      RESULTS: The incidences of nontraumatic and traumatic OHCA were 7.91 (95%
      confidence interval [CI]: 7.52-8.30) and 2.67 (95% CI: 2.49-2.85) per 100 000
      person years. In nontraumatic OHCA, unadjusted survival was higher in pediatric
      EDs than general EDs (33.8% vs 18.9%, P < .001). The adjusted odds ratio of
      survival in pediatric versus general EDs was 2.2 (95% CI: 1.7-2.8). Children with
      traumatic OHCA had similar survival in pediatric and general EDs (31.7% vs 26.1%,
      P = .14; adjusted odds ratio = 1.3 [95% CI: 0.8-2.1]). CONCLUSIONS: In a
      nationally representative sample, survival from nontraumatic OHCA was higher in
      pediatric EDs than general EDs. Survival did not differ in traumatic OHCA.
      Identifying the features of pediatric ED OHCA care leading to higher survival
      could be translated into improved survival for children nationally.

PMID- 29367205
TI  - Predicting outcomes in aneurysmal subarachnoid haemorrhage.

PMID- 29367206
TI  - Global elimination of viral hepatitis and hepatocellular carcinoma: opportunities
      and challenges.

PMID- 29367207
TI  - Non-alcoholic steatohepatitis pathogenesis: sublethal hepatocyte injury as a
      driver of liver inflammation.
AB  - A subset of patients with non-alcoholic fatty liver disease develop an
      inflammatory condition, termed non-alcoholic steatohepatitis (NASH). NASH is
      characterised by hepatocellular injury, innate immune cell-mediated inflammation
      and progressive liver fibrosis. The mechanisms whereby hepatic inflammation
      occurs in NASH remain incompletely understood, but appear to be linked to the
      proinflammatory microenvironment created by toxic lipid-induced hepatocyte
      injury, termed lipotoxicity. In this review, we discuss the signalling pathways
      induced by sublethal hepatocyte lipid overload that contribute to the
      pathogenesis of NASH. Furthermore, we will review the role of proinflammatory,
      proangiogenic and profibrotic hepatocyte-derived extracellular vesicles as
      disease biomarkers and pathogenic mediators during lipotoxicity. We also review
      the potential therapeutic strategies to block the feed-forward loop between
      sublethal hepatocyte injury and liver inflammation.

PMID- 29367209
TI  - The Complement C3a-C3aR Axis Promotes Development of Thoracic Aortic Dissection
      via Regulation of MMP2 Expression.
AB  - Thoracic aortic dissection (TAD), once ruptured, is devastating to patients, and
      no effective pharmaceutical therapy is available. Anaphylatoxins released by
      complement activation are involved in a variety of diseases. However, the role of
      the complement system in TAD is unknown. We found that plasma levels of C3a, C4a,
      and C5a were significantly increased in patients with TAD. Elevated circulating
      C3a levels were also detected in the developmental process of mouse TAD, which
      was induced by beta-aminopropionitrile monofumarate (BAPN) treatment, with
      enhanced expression of C1q and properdin in mouse dissected aortas. These
      findings indicated activation of classical and alternative complement pathways.
      Further, expression of C3aR was obviously increased in smooth muscle cells of
      human and mouse dissected aortas, and knockout of C3aR notably inhibited BAPN
      induced formation and rupture of TAD in mice. C3aR antagonist administered pre-
      and post-BAPN treatment attenuated the development of TAD. We found that C3aR
      knockout decreased matrix metalloproteinase 2 (MMP2) expression in BAPN-treated
      mice. Additionally, recombinant C3a stimulation enhanced MMP2 expression and
      activation in smooth muscle cells that were subjected to mechanical stretch.
      Finally, we generated MMP2-knockdown mice by in vivo MMP2 short hairpin RNA
      delivery using recombinant adeno-associated virus and found that MMP2 deficiency
      significantly reduced the formation of TAD. Therefore, our study suggests that
      the C3a-C3aR axis contributes to the development of TAD via regulation of MMP2
      expression. Targeting the C3a-C3aR axis may represent a strategy for inhibiting
      the formation of TAD.

PMID- 29367208
TI  - IL-10 Paradoxically Promotes Autoimmune Neuropathy through S1PR1-Dependent CD4+ T
      Cell Migration.
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is a debilitating
      condition caused by autoimmune demyelination of peripheral nerves. CIDP is
      associated with increased IL-10, a cytokine with well-described anti-inflammatory
      effects. However, the role of IL-10 in CIDP is unclear. In this study, we
      demonstrate that IL-10 paradoxically exacerbates autoimmunity against peripheral
      nerves. In IL-10-deficient mice, protection from neuropathy was associated with
      an accrual of highly activated CD4+ T cells in draining lymph nodes and absence
      of infiltrating immune cells in peripheral nerves. Accumulated CD4+ T cells in
      draining lymph nodes of IL-10-deficient mice expressed lower sphingosine-1
      phosphate receptor 1 (S1pr1), a protein important in lymphocyte egress.
      Additionally, IL-10 stimulation in vitro induced S1pr1 expression in lymph node
      cells in a STAT3-dependent manner. Together, these results delineate a novel
      mechanism in which IL-10-induced STAT3 increases S1pr1 expression and CD4+ T cell
      migration to accelerate T cell-mediated destruction of peripheral nerves.

PMID- 29367211
TI  - Monosodium Urate Crystals Generate Nuclease-Resistant Neutrophil Extracellular
      Traps via a Distinct Molecular Pathway.
AB  - Neutrophil extracellular traps (NETs) and the cell death associated with it
      (NETosis) have been implicated in numerous diseases. Mechanistic studies of
      NETosis have typically relied on nonphysiological stimuli, such as PMA. The human
      disease of gout is caused by monosodium urate (MSU) crystals. We observed that
      DNA consistent with NETs is present in fluid from acutely inflamed joints of gout
      patients. NETs also coat the crystals found in uninflamed tophi of chronic gout
      patients. We developed a quantitative, live cell imaging assay, which measures
      the key features of NETosis, namely, cell death and chromatin decondensation. We
      show that MSU and other physiologically relevant crystals induce NETosis through
      a molecular pathway that is distinct from PMA and Candida hyphae. Crystals
      interact with lysosomes to induce NADPH oxidase-independent cell death, with
      postmortem chromatin decondensation mediated by neutrophil elastase. The
      resulting MSU-induced NETs are enriched for actin and are resistant to serum and
      DNase degradation. These findings demonstrate a distinct physiological NETosis
      pathway in response to MSU crystals, which coats MSU crystals in DNA that
      persists in tissues as gouty tophi.

PMID- 29367210
TI  - CD8+ T Cells Lack Local Signals To Produce IFN-gamma in the Skin during
      Leishmania Infection.
AB  - Resolution of leishmaniasis depends upon parasite control and limiting
      inflammation. CD4+ Th1 cells are required to control parasites, whereas CD8+ T
      cells play a dual role: they promote Th1 cell differentiation but can also
      increase inflammation at the site of infection as a consequence of cytolysis.
      Although CD8+ T cells taken from leishmanial lesions are cytolytic, in this
      study, we showed that only a few CD8+ T cells produced IFN-gamma.
      Correspondingly, only low levels of IL-12 and/or IL-12 mRNA were present in
      lesions from infected mice, as well as patients. Addition of IL-12 increased IFN
      gamma production by CD8+ T cells isolated from leishmanial lesions, suggesting
      that a lack of IL-12 at the site of infection limits IFN-gamma production by CD8+
      T cells. To determine whether CD8+ T cells could promote resistance in vivo if IL
      12 was present, we administered IL-12 to Leishmania-infected RAG mice
      reconstituted with CD8+ T cells. IL-12 treatment increased the ability of CD8+ T
      cells to make IFN-gamma, but CD8+ T cells still failed to control the parasites.
      Furthermore, despite the ability of CD8+ T cells to promote immunity to secondary
      infections, we also found that CD8+ T cells from immune mice were unable to
      control Leishmania in RAG mice. Taken together, these results indicate that
      lesional CD8+ T cells fail to make IFN-gamma because of a deficit in IL-12 but
      that, even with IL-12, CD8+ T cells are unable to control Leishmania in the
      absence of CD4+ T cells.

PMID- 29367212
TI  - Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single
      Ventricle Congenital Heart Disease.
AB  - RATIONALE: Intracoronary administration of cardiosphere-derived cells (CDCs) in
      patients with single ventricles resulted in a short-term improvement in cardiac
      function. OBJECTIVE: To test the hypothesis that CDC infusion is associated with
      improved cardiac function and reduced mortality in patients with heart failure.
      METHODS AND RESULTS: We evaluated the effectiveness of CDCs using an integrated
      cohort study in 101 patients with single ventricles, including 41 patients who
      received CDC infusion and 60 controls treated with staged palliation alone. Heart
      failure with preserved ejection fraction (EF) or reduced EF was stratified by the
      cardiac function after surgical reconstruction. The main outcome measure was to
      evaluate the magnitude of improvement in cardiac function and all-cause mortality
      at 2 years. Animal studies were conducted to clarify the underlying mechanisms of
      heart failure with preserved EF and heart failure with reduced EF phenotypes. At
      2 years, CDC infusion increased ventricular function (stage 2: +8.4+/-10.0%
      versus +1.6+/-6.4%, P=0.03; stage 3: +7.9+/-7.5% versus -1.1+/-5.5%, P<0.001)
      compared with controls. In all available follow-up data, survival did not differ
      between the 2 groups (log-rank P=0.225), whereas overall patients treated by CDCs
      had lower incidences of late failure (P=0.022), adverse events (P=0.013), and
      catheter intervention (P=0.005) compared with controls. CDC infusion was
      associated with a lower risk of adverse events (hazard ratio, 0.411; 95% CI,
      0.179-0.942; P=0.036). Notably, CDC infusion reduced mortality (P=0.038) and late
      complications (P<0.05) in patients with heart failure with reduced EF but not
      with heart failure with preserved EF. CDC-treated rats significantly reversed
      myocardial fibrosis with differential collagen deposition and inflammatory
      responses between the heart failure phenotypes. CONCLUSIONS: CDC administration
      in patients with single ventricles showed favorable effects on ventricular
      function and was associated with reduced late complications except for all-cause
      mortality after staged procedures. Patients with heart failure with reduced EF
      but not heart failure with preserved EF treated by CDCs resulted in significant
      improvement in clinical outcome. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifiers: NCT01273857 and NCT01829750.

PMID- 29367213
TI  - Trained Innate Immunity as a Novel Mechanism Linking Infection and the
      Development of Atherosclerosis.
AB  - RATIONALE: There is strong epidemiological evidence for an association between
      acute and chronic infections and the occurrence of atherosclerotic cardiovascular
      disease. The underlying pathophysiological mechanisms remain unclear. Monocyte
      derived macrophages are the most abundant immune cells in atherosclerotic
      plaques. It has recently been established that monocytes/macrophages can develop
      a long-lasting proinflammatory phenotype after brief stimulation with micro
      organisms or microbial products, which has been termed trained immunity.
      OBJECTIVE: The aim of this study is to assess whether trained immunity mediates
      the link between infections and atherosclerotic cardiovascular disease. METHODS
      AND RESULTS: Brief exposure of monocytes to various micro-organisms results in
      the development of macrophages with a persistent proinflammatory phenotype: this
      represents a de facto nonspecific innate immune memory, which has been termed
      trained immunity. This is mediated by epigenetic reprogramming at the level of
      histone methylation and a profound rewiring of intracellular metabolism. Although
      this mechanism offers powerful protection against reinfection, trained
      macrophages display an atherogenic phenotype in terms of cytokine production and
      foam cell formation. Trained monocytes are present up to 3 months after
      experimental infection in humans. Moreover, a trained immunity phenotype is
      present in patients with established atherosclerosis. CONCLUSIONS: We propose
      that trained immunity provides the missing mechanistic link that explains the
      association between infections and atherosclerosis. Therefore, pharmacological
      modulation of trained immunity has the potential to prevent infection-related
      atherosclerotic cardiovascular disease in the future.

PMID- 29367214
TI  - Tropical bird species have less variable body sizes.
AB  - Ecologists have often predicted that species' niche breadths should decline
      towards the Equator. Dan Janzen arrived at this prediction based on climatic
      constraints, while Robert MacArthur argued that a latitudinal gradient in
      resource specialization drives the pattern. This idea has some support when it
      comes to thermal niches, but has rarely been explored for other niche dimensions.
      Body size is linked to niche dimensions related to diet, competition and
      environmental tolerance in vertebrates. We identified 68 pairs of tropical and
      nontropical sister bird species using a comprehensive phylogeny and used the
      VertNet specimen database to ask whether tropical birds have lower intraspecific
      body-size variation than their nontropical sister species. Our results show that
      tropical species have less intraspecific variability in body mass ([Formula: see
      text]; p = 0.009). Variation in body-size variability was poorly explained by
      both abiotic and biotic drivers; thus the mechanisms underlying the pattern are
      still unclear. The lower variation in body size of tropical bird species may have
      evolved in response to more stable climates and resource environments.

PMID- 29367215
TI  - Social manipulation of sperm competition intensity reduces seminal fluid gene
      expression.
AB  - A considerable body of evidence supports the prediction that males should
      increase their expenditure on the ejaculate in response to sperm competition
      risk. The prediction that they should reduce their expenditure with increasing
      sperm competition intensity is less well supported. Moreover, most studies have
      documented plasticity in sperm numbers. Here we show that male crickets
      Teleogryllus oceanicus exhibit reduced seminal fluid gene expression and
      accessory gland mass in response to elevated sperm competition intensity.
      Together with previous research, our findings suggest that strategic adjustments
      in seminal fluid composition contribute to competitive fertilization success in
      this species.

PMID- 29367216
TI  - Michael Farquhar: Sleep, the best medicine.

PMID- 29367217
TI  - Antibiotics for simple skin abscesses: the new evidence in perspective.

PMID- 29367218
TI  - Orthostatic blood pressure recovery patterns in suspected syncope in the
      emergency department.
AB  - INTRODUCTION: Orthostasis is a frequent trigger for (pre)syncope but some forms
      of orthostatic (pre)syncope have a worse prognosis than others. Routine
      assessment of orthostatic BP in the ED can detect classic orthostatic
      hypotension, but often misses these other forms of orthostatic (pre)syncope. This
      study aimed to determine the frequency of abnormal orthostatic BP recovery
      patterns in patients with (pre)syncope by using continuous non-invasive BP
      monitoring. METHODS: We performed a prospective cohort study in suspected
      patients with (pre)syncope in the ED of a tertiary care teaching hospital between
      January and August 2014. Orthostatic BP was measured during the active lying-to
      standing test with Nexfin, a continuous non-invasive finger arterial pressure
      measurement device. Orthostatic BP recovery patterns were defined as normal BP
      recovery, initial orthostatic hypotension, delayed BP recovery, classic
      orthostatic hypotension and reflex-mediated hypotension. RESULTS: Of 116 patients
      recruited, measurements in 111 patients (age 63 years, 51% male) were suitable
      for analysis. Classic orthostatic hypotension was the most prevalent abnormal BP
      pattern (19%), but only half of the patients received a final diagnosis of
      orthostatic hypotension. Initial orthostatic hypotension and delayed BP recovery
      were present in 20% of the patients with (pre)syncope of whom 45% were diagnosed
      as unexplained syncope. Reflex-mediated hypotension was present in 4% of the
      patients. CONCLUSION: Continuous non-invasive BP measurement can potentially
      identify more specific and concerning causes of orthostatic (pre)syncope. Correct
      classification is important because of different short-term and long-term
      clinical implications.

PMID- 29367219
TI  - Parapedicular vertebral augmentation with polymethylmetacrylate for pedicle screw
      loosening.
AB  - A 71-year-old man who had a L1/S1 posterior fusion revision surgery complained of
      increasing back pain 5 weeks after the open surgical procedure. The pain was
      initially estimated at 9/10 on the visual analog scale (VAS) and thought to be
      related to a right-sided L2 screw loosening. A right parapedicular vertebroplasty
      was performed and polymethylmethacrylate cement was instilled around the right
      pedicle screw, filling the anterior two-thirds of the vertebral body. On
      postvertebroplasty day 1, the patient had significant improvement in his low back
      pain. The pain further decreased at 1 and 3 months after the intervention (2/10
      on the VAS). Vertebroplasty is a minimally invasive, accessible, effective, and
      long lasting treatment for compression fractures. We believe that this technique
      could also be indicated to treat pain related to low grade screw loosening in
      properly selected patients.

PMID- 29367220
TI  - A mesh masquerading as malignancy: a cancer misdiagnosed.
AB  - After a positive faecal occult blood test, a 60-year-old woman underwent a
      screening colonoscopy which identified a malignant-looking ulcer in the ascending
      colon. Biopsies from the lesion were inconclusive. A subsequent CT scan of the
      abdomen and pelvis commented on a polypoid lesion in the ascending colon. A
      colorectal cancer multidisciplinary team discussion concluded that a right
      hemicolectomy was indicated as the lesion was suspicious for malignancy.
      Intraoperatively, there was a firm ascending colon mass adherent to the abdominal
      wall, which was resected with clear margins. There were no other complications,
      and the patient was discharged without further issues. Histopathology from the
      retrieved specimen revealed a complete absence of malignancy, but rather,
      inflamed granulation tissue with 'reaction to foreign birefringent material'
      likely to represent a mesh from an incisional hernia repair 9 years previously.
      The patient is currently recovering well without complication.

PMID- 29367221
TI  - Severe systemic inflammatory response syndrome immediately after spinal surgery
      in a patient with axial gout.
AB  - We report a 55-year-old man with gouty arthritis who developed a 3-month history
      of low back pain, gradual lower extremities weakness and urinary incontinence.
      Lumbar MRI showed an exophytic lesion at L3-L4. Immediately after spinal
      decompression surgery, he developed fever, disorientation, polyarthritis, acute
      kidney injury and leucocytosis. He was treated with multiple antimicrobial agents
      for presumed spinal abscess but did not improve. Multiple body site cultures were
      negative. Aspiration of the sacroiliac joint revealed the presence of monosodium
      uric acid crystals. A diagnosis of acute gout was done, and he was treated with
      high-dose intravenous methylprednisolone and colchicine. Within 48 hours, he had
      a remarkable clinical improvement. At discharge, neurological and laboratory
      abnormalities had resolved. Awareness of risk factors for axial gout and a high
      degree of suspicion are important to establish a prompt diagnosis and treatment
      to prevent severe complications as seen in this case.

PMID- 29367222
TI  - Left ventricular free-wall rupture that occurred during a cardiopulmonary
      exercise test.
AB  - Although exercise testing has become a standard procedure before discharge for
      patients with acute coronary syndrome, a fatal accident during the test is
      extremely rare. A 60-year-old man was admitted for a non-ST-segment elevation
      myocardial infarction. A coronary angiogram showed stenosis at the distal lesion
      of the circumflex, and a balloon angioplasty was performed. His recovery was
      smooth, and a cardiopulmonary exercise test was performed 5 days after admission.
      At 2.5 metabolic equivalents, he suddenly went into cardiac arrest, and
      percutaneous cardiopulmonary support was initiated. Echocardiography revealed the
      presence of a large amount of pericardial effusion, and emergency cardiac surgery
      was performed to repair the free-wall rupture. This highlights the importance of
      careful monitoring of patients with percutaneous coronary intervention during
      cardiopulmonary exercise testing.

PMID- 29367223
TI  - The curse of relieving pain.
AB  - A 39-year-old woman with a history of chronic back pain due to spinal
      haemangiomas, multiple malignancies and depression was brought by Emergency
      medical servicesS to the emergency centre (EC) after being found unresponsive on
      the bathroom floor. The patient had an exacerbation of her back pain the previous
      day for which she admitted to taking double her usual dose of oxycodone, in
      addition to alprazolam, lorazepam, diphenhydramine and a glass of wine. She
      reported that she lost consciousness and was down for over 8 hours. In the EC,
      she complained of right forearm pain which was accompanied by mild diffuse soft
      tissue swelling and decreased sensation in the right hand. Radial pulse was
      intact. Creatine kinase was found to be at 4663 U/L. The patient was found to
      have acute compartment syndrome and underwent emergent forearm fasciotomy. She
      eventually regained full function of the right arm.

PMID- 29367224
TI  - The effect of a therapeutic lithium level on a stroke-related cerebellar tremor.
AB  - Lithium is a mood stabiliser used in the treatment of acute mania, bipolar
      disorder and as augmentation for unipolar major depression. Tremor is a common
      adverse effect associated with lithium at both therapeutic and toxic serum
      levels. We present a case of dose-dependent changes in the quality and intensity
      of a stroke-related, chronic cerebellar tremor with lithium treatment at serum
      levels within the therapeutic range. On admission, the patient in this case had a
      baseline fine, postural tremor, which increased in frequency and evolved to
      include myoclonic jerks once lithium therapy was initiated. Although the
      patient's serum lithium level was never in the toxic range, his tremor returned
      to baseline on reduction of his serum lithium level. This case highlights that a
      pre-existing, baseline tremor may lower the threshold for developing myoclonus.
      It also suggests that caution may be warranted with lithium therapy in the
      setting of known cerebellar disease.

PMID- 29367225
TI  - Super obesity is not necessarily a contraindication to deep inferior epigastric
      perforator flap breast reconstruction.
AB  - The deep inferior epigastric perforator (DIEP) flap is widely recognised as a
      safe and reliable flap for use as a first-choice option in autologous tissue
      breast reconstruction. Patients with obesity represent a challenging group for
      autologous breast reconstruction, as they are at increased risk of developing
      major and minor complications in comparison with patients with normal weight. We
      report a 59-year-old woman with super obesity, who presented to our department
      with right breast skin necrosis after implant reconstruction following mastectomy
      for right breast cancer. After implant removal and local treatment with both
      surgical debridement and negative pressure wound therapy, the patient
      successfully underwent a DIEP flap breast reconstruction. We conclude that super
      obesity should not be a contraindication to DIEP flap breast reconstruction.

PMID- 29367226
TI  - Optic nerve grey crescent: an assessment using swept-source OCT.

PMID- 29367227
TI  - Closed gastroschisis with left defect: a rare variant.

PMID- 29367228
TI  - TRPing out Platelet Calcium: TRPM7 (Transient Receptor Potential Melastatin-Like
      7) Modulates Calcium Mobilization and Platelet Function via Phospholipase C
      Interactions.

PMID- 29367229
TI  - PAR4 (Protease-Activated Receptor 4): PARticularly Important 4 Antiplatelet
      Therapy.

PMID- 29367230
TI  - The Importance of Sex in the Stress-Heart Disease Relationship and the Potential
      Contribution of Gender to Future Research.

PMID- 29367231
TI  - ATVB Named Lecture Review-Insight Into Author: Jeffrey I. Weitz, MD.

PMID- 29367232
TI  - High-Density Lipoprotein Function in Cardiovascular Disease and Diabetes
      Mellitus.

PMID- 29367233
TI  - Control of Retrograde Signaling by Rapid Turnover of GENOMES UNCOUPLED1.
AB  - The exchange of signals between cellular compartments coordinates development and
      differentiation, modulates metabolic pathways, and triggers responses to
      environmental conditions. The proposed central regulator of plastid-to-nucleus
      retrograde signaling, GENOMES UNCOUPLED1 (GUN1), is present at very low levels,
      which has hampered the discovery of its precise molecular function. Here, we show
      that the Arabidopsis (Arabidopsis thaliana) GUN1 protein accumulates to
      detectable levels only at very early stages of leaf development, where it
      functions in the regulation of chloroplast biogenesis. GUN1 mRNA is present at
      high levels in all tissues, but GUN1 protein undergoes rapid degradation (with an
      estimated half-life of ~4 h) in all tissues where chloroplast biogenesis has been
      completed. The rapid turnover of GUN1 is controlled mainly by the chaperone
      ClpC1, suggesting degradation of GUN1 by the Clp protease. Degradation of GUN1
      slows under stress conditions that alter retrograde signaling, thus ensuring that
      the plant has sufficient GUN1 protein. We also find that the pentatricopeptide
      repeat motifs of GUN1 are important determinants of GUN1 stability. Moreover,
      overexpression of GUN1 causes an early flowering phenotype, suggesting a function
      of GUN1 in developmental phase transitions beyond chloroplast biogenesis. Taken
      together, our results provide new insight into the regulation of GUN1 by
      proteolytic degradation, uncover its function in early chloroplast biogenesis,
      and suggest a role in developmental phase transitions.

PMID- 29367234
TI  - ER-Anchored Transcription Factors bZIP17 and bZIP28 Regulate Root Elongation.
AB  - The unfolded protein response (UPR) is a eukaryotic transcriptional regulatory
      network that is activated upon the accumulation of malformed proteins in the
      endoplasmic reticulum (ER). In Arabidopsis (Arabidopsis thaliana), three bZIP
      transcription factors modulate the UPR: bZIP17, bZIP28, and bZIP60. Although
      bZIP28 and bZIP60 have been relatively well studied, the physiological and
      transcriptional roles of bZIP17 remain largely unknown. Here, we generated a
      double knockout mutant of bZIP17 and bZIP28 to elucidate the function of bZIP17.
      The mutant plant exhibited multiple developmental defects, including markedly
      reduced root elongation and constantly overinduced bZIP60 activity, indicating
      the essential roles of bZIP17 and bZIP28 in plant development and UPR modulation.
      Extended analysis of the transcriptomes of three double knockout mutants of
      bZIP17, bZIP28, and bZIP60 revealed that bZIP28 and bZIP60 are the major
      activators of the canonical induced UPR. By contrast, bZIP17 functions with
      bZIP28 to mediate the noninducible expression of multiple genes involved in cell
      growth, particularly to sustain their expression under stress conditions. Our
      study reveals pivotal roles of bZIP17 in the plant UPR and vegetative
      development, with functional redundancy to bZIP28.

PMID- 29367235
TI  - Knockdown of Rice MicroRNA166 Confers Drought Resistance by Causing Leaf Rolling
      and Altering Stem Xylem Development.
AB  - MicroRNAs are 19- to 22-nucleotide small noncoding RNAs that have been implicated
      in abiotic stress responses. In this study, we found that knockdown of
      microRNA166, using the Short Tandem Target Mimic (STTM) system, resulted in
      morphological changes that confer drought resistance in rice (Oryza sativa). From
      a large-scale screen for miRNA knockdown lines in rice, we identified miR166
      knockdown lines (STTM166); these plants exhibit a rolled-leaf phenotype, which is
      normally displayed by rice plants under drought stress. The leaves of STTM166
      rice plants had smaller bulliform cells and abnormal sclerenchymatous cells,
      likely causing the rolled-leaf phenotype. The STTM166 plants had reduced stomatal
      conductance and showed decreased transpiration rates. The STTM166 lines also
      exhibited altered stem xylem and decreased hydraulic conductivity, likely due to
      the reduced diameter of the xylem vessels. Molecular analyses identified rice
      HOMEODOMAIN CONTAINING PROTEIN4 (OsHB4), a member of HD-Zip III gene family, as a
      major target of miR166; moreover, rice plants overexpressing a miR166-resistant
      form of OsHB4 resembled the STTM166 plants, including leaf rolling and higher
      drought resistance. The genes downstream of miR166-OsHB4 consisted of
      polysaccharide synthesis-related genes that may contribute to cell wall formation
      and vascular development. Our results suggest that drought resistance in rice can
      be increased by manipulating miRNAs, which leads to developmental changes, such
      as leaf rolling and reduced diameter of the xylem, that mimic plants' natural
      responses to water-deficit stress.

PMID- 29367236
TI  - Stresses and strains on the human fetal skeleton during development.
AB  - Mechanical forces generated by fetal kicks and movements result in stimulation of
      the fetal skeleton in the form of stress and strain. This stimulation is known to
      be critical for prenatal musculoskeletal development; indeed, abnormal or absent
      movements have been implicated in multiple congenital disorders. However, the
      mechanical stress and strain experienced by the developing human skeleton in
      utero have never before been characterized. Here, we quantify the biomechanics of
      fetal movements during the second half of gestation by modelling fetal movements
      captured using novel cine-magnetic resonance imaging technology. By tracking
      these movements, quantifying fetal kick and muscle forces, and applying them to
      three-dimensional geometries of the fetal skeleton, we test the hypothesis that
      stress and strain change over ontogeny. We find that fetal kick force increases
      significantly from 20 to 30 weeks' gestation, before decreasing towards term.
      However, stress and strain in the fetal skeleton rises significantly over the
      latter half of gestation. This increasing trend with gestational age is important
      because changes in fetal movement patterns in late pregnancy have been linked to
      poor fetal outcomes and musculoskeletal malformations. This research represents
      the first quantification of kick force and mechanical stress and strain due to
      fetal movements in the human skeleton in utero, thus advancing our understanding
      of the biomechanical environment of the uterus. Further, by revealing a potential
      link between fetal biomechanics and skeletal malformations, our work will
      stimulate future research in tissue engineering and mechanobiology.

PMID- 29367237
TI  - The complexity of high-frequency electric fields degrades electrosensory inputs:
      implications for the jamming avoidance response in weakly electric fish.
AB  - Sensory systems encode environmental information that is necessary for adaptive
      behavioural choices, and thus greatly influence the evolution of animal behaviour
      and the underlying neural circuits. Here, we evaluate how the quality of sensory
      information impacts the jamming avoidance response (JAR) in weakly electric fish.
      To sense their environment, these fish generate an oscillating electric field:
      the electric organ discharge (EOD). Nearby fish with similar EOD frequencies
      perform the JAR to increase the difference between their EOD frequencies, i.e.
      their difference frequency (DF). The fish determines the sign of the DF: when it
      has a lower frequency (DF > 0), EOD frequency is decreased and vice versa. We
      study the sensory basis of the JAR in two species: Apteronotus leptorhynchus have
      a high frequency (ca 1000 Hz), spatio-temporally heterogeneous electric field,
      whereas Eigenmannia sp. have a low frequency (ca 300 Hz), spatially uniform
      field. We show that the increased complexity of the Apteronotus field decreases
      the reliability of sensory cues used to determine the DF. Interestingly,
      Apteronotus responds to all JAR stimuli by increasing EOD frequency, having lost
      the neural pathway that produces JAR-related decreases in EOD frequency. Our
      results suggest that electric field complexity may have influenced the evolution
      of the JAR by degrading the related sensory information.

PMID- 29367238
TI  - Overcoming hydrodynamic challenges in suspension feeding by juvenile Mya arenaria
      clams.
AB  - We present some of the few suspension-feeding measurements and to our knowledge
      the first velocity-field measurements for early post-settlement juvenile bivalve
      clams. We verify and extend our experimental results with numerical simulations.
      For 1.8-2.8 mm shell length Mya arenaria clams, pumping rates ranged 0.03-0.22
      MUl s-1, inhalant siphon Reynolds numbers (Re) ranged 0.16-0.79 and mean inhalant
      velocities ranged 0.8-3.2 mm s-1 Owing to the low Re at which they pump and the
      small diameters of their siphons, juvenile clams are subject to unique
      hydrodynamic challenges, including high siphon resistance and susceptibility to
      refiltration. At least three features of juvenile clam siphons differentiate them
      from those of adults-shorter inhalant siphon length, a more rapid increase in
      inhalant siphon diameter with shell length, and the presence of a prominent
      exhalant siphon extension. These features are probably adaptations to the
      challenges of suspension feeding at low Re.

PMID- 29367239
TI  - Towards personalized computational oncology: from spatial models of tumour
      spheroids, to organoids, to tissues.
AB  - A main goal of mathematical and computational oncology is to develop quantitative
      tools to determine the most effective therapies for each individual patient. This
      involves predicting the right drug to be administered at the right time and at
      the right dose. Such an approach is known as precision medicine. Mathematical
      modelling can play an invaluable role in the development of such therapeutic
      strategies, since it allows for relatively fast, efficient and inexpensive
      simulations of a large number of treatment schedules in order to find the most
      effective. This review is a survey of mathematical models that explicitly take
      into account the spatial architecture of three-dimensional tumours and address
      tumour development, progression and response to treatments. In particular, we
      discuss models of epithelial acini, multicellular spheroids, normal and tumour
      spheroids and organoids, and multi-component tissues. Our intent is to showcase
      how these in silico models can be applied to patient-specific data to assess
      which therapeutic strategies will be the most efficient. We also present the
      concept of virtual clinical trials that integrate standard-of-care patient data,
      medical imaging, organ-on-chip experiments and computational models to determine
      personalized medical treatment strategies.

PMID- 29367241
TI  - Temporal variation of human encounters and the number of locations in which they
      occur: a longitudinal study of Hong Kong residents.
AB  - Patterns of social contact between individuals are important for the transmission
      of many pathogens and shaping patterns of immunity at the population scale. To
      refine our understanding of how human social behaviour may change over time, we
      conducted a longitudinal study of Hong Kong residents. We recorded the social
      contact patterns for 1450 individuals, up to four times each between May 2012 and
      September 2013. We found individuals made contact with an average of 12.5 people
      within 2.9 geographical locations, and spent an average estimated total duration
      of 9.1 h in contact with others during a day. Distributions of the number of
      contacts and locations in which contacts were made were not significantly
      different between study waves. Encounters were assortative by age, and the age
      mixing pattern was broadly consistent across study waves. Fitting regression
      models, we examined the association of contact rates (number of contacts, total
      duration of contact, number of locations) with covariates and calculated the
      inter- and intra-participant variation in contact rates. Participant age was
      significantly associated with the number of contacts made, the total duration of
      contact and the number of locations in which contact occurred, with children and
      parental-age adults having the highest rates of contact. The number of contacts
      and contact duration increased with the number of contact locations. Intra
      individual variation in contact rate was consistently greater than inter
      individual variation. Despite substantial individual-level variation, remarkable
      consistency was observed in contact mixing at the population scale. This suggests
      that aggregate measures of mixing behaviour derived from cross-sectional
      information may be appropriate for population-scale modelling purposes, and that
      if more detailed models of social interactions are required for improved public
      health modelling, further studies are needed to understand the social processes
      driving intra-individual variation.

PMID- 29367240
TI  - Quantitative approaches to energy and glucose homeostasis: machine learning and
      modelling for precision understanding and prediction.
AB  - Obesity is a major global public health problem. Understanding how energy
      homeostasis is regulated, and can become dysregulated, is crucial for developing
      new treatments for obesity. Detailed recording of individual behaviour and new
      imaging modalities offer the prospect of medically relevant models of energy
      homeostasis that are both understandable and individually predictive. The
      profusion of data from these sources has led to an interest in applying machine
      learning techniques to gain insight from these large, relatively unstructured
      datasets. We review both physiological models and machine learning results across
      a diverse range of applications in energy homeostasis, and highlight how
      modelling and machine learning can work together to improve predictive ability.
      We collect quantitative details in a comprehensive mathematical supplement. We
      also discuss the prospects of forecasting homeostatic behaviour and stress the
      importance of characterizing stochasticity within and between individuals in
      order to provide practical, tailored forecasts and guidance to combat the spread
      of obesity.

PMID- 29367242
TI  - A deep learning approach to estimate stress distribution: a fast and accurate
      surrogate of finite-element analysis.
AB  - Structural finite-element analysis (FEA) has been widely used to study the
      biomechanics of human tissues and organs, as well as tissue-medical device
      interactions, and treatment strategies. However, patient-specific FEA models
      usually require complex procedures to set up and long computing times to obtain
      final simulation results, preventing prompt feedback to clinicians in time
      sensitive clinical applications. In this study, by using machine learning
      techniques, we developed a deep learning (DL) model to directly estimate the
      stress distributions of the aorta. The DL model was designed and trained to take
      the input of FEA and directly output the aortic wall stress distributions,
      bypassing the FEA calculation process. The trained DL model is capable of
      predicting the stress distributions with average errors of 0.492% and 0.891% in
      the Von Mises stress distribution and peak Von Mises stress, respectively. This
      study marks, to our knowledge, the first study that demonstrates the feasibility
      and great potential of using the DL technique as a fast and accurate surrogate of
      FEA for stress analysis.

PMID- 29367243
TI  - Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given
      Individually, Sequentially, or in Combination.
AB  - Recombinant soluble HIV-1 envelope glycoprotein (Env) SOSIP trimers are a design
      platform for inducing broadly neutralizing antibodies (bNAbs) by vaccination. To
      date, these and alternative designs of native-like trimers, given singly or in
      pairs, have not induced bNAbs in test animals such as rabbits or macaques. Here,
      we have evaluated whether trivalent and tetravalent combinations of SOSIP trimers
      from clades A, B, and C, delivered simultaneously or sequentially, induce better
      neutralizing antibody responses in rabbits than when given alone. None of the
      tested formulations led to the induction of bNAbs. We found that BG505 clade A
      trimers dominated the autologous NAb responses induced by combinations, which
      probably relates to the presence of immunodominant glycan holes on the BG505
      trimer. Furthermore, autologous NAb responses to all individual trimers were
      reduced when they were delivered in combinations compared with when delivered
      alone, suggesting that immunogen interference had occurred. Finally, in a
      sequential regimen, a heterologous clade C trimer cross-boosted NAb responses
      that were primed by earlier immunizations with clade A and B trimers. Taken
      together, these findings should allow us to improve the design of immunization
      regimens based on native-like HIV-1 Env trimers.IMPORTANCE A successful HIV-1
      vaccine most probably requires a trimeric envelope glycoprotein (Env) component,
      as Env is the only viral protein on the surface of the virus and therefore the
      only target for neutralizing antibodies. Native-like Env trimers can induce
      strain-specific neutralizing antibodies but not yet broadly neutralizing
      antibodies. To try to broaden the antibody response, we immunized rabbits with
      soluble native-like Env trimers from three different clades using monovalent,
      multivalent, and sequential regimens. We found that the neutralizing antibody
      response against each immunogen was reduced when the immunogens were delivered in
      combination or sequentially compared to the monovalent regimen. In contrast, when
      the Env trimers from different clades were delivered sequentially, the
      neutralizing antibody response could be cross-boosted. Although the combination
      of native-like Env trimers from different clades did not induce broadly
      neutralizing antibodies, the results provide clues on how to use native-like
      trimers in vaccination experiments.

PMID- 29367244
TI  - Hepatitis B Virus Subverts the Autophagy Elongation Complex Atg5-12/16L1 and Does
      Not Require Atg8/LC3 Lipidation for Viral Maturation.
AB  - Previous studies indicated that hepatitis B virus (HBV) stimulates autophagy to
      favor its production. To understand how HBV co-opts autophagy as a proviral
      machinery, we studied the roles of key autophagy proteins in HBV-replicating
      liver cell cultures. RNA interference-mediated silencing of Atg5, Atg12, and
      Atg16L1, which promote autophagophore expansion and LC3 membrane conjugation,
      interfered with viral core/nucleocapsid (NC) formation/stability and strongly
      diminished virus yields. Concomitantly, the core/NC membrane association and
      their sorting to envelope-positive compartments were perturbed. A close
      inspection of the HBV/autophagy cross talk revealed that the virus depended on
      Atg12 covalently conjugated to Atg5. In support of this finding, HBV required the
      E2-like enzymes Atg10 and Atg3, which catalyze or facilitate Atg5-12 conjugation,
      respectively. Atg10 and Atg3 knockdowns decreased HBV production, while Atg3
      overexpression increased virus yields. Mapping analyses demonstrated that the HBV
      core protein encountered the Atg5-12/16L1 complex via interaction with the
      intrinsically disordered region of the Atg12 moiety that is dispensable for
      autophagy function. The role of Atg12 in HBV replication was confirmed by its
      incorporation into virions. Although the Atg5-12/16L1 complex and Atg3 are
      essential for LC3 lipidation and, thus, for autophagosome maturation and closure,
      HBV propagation did not require LC3. Silencing of LC3B, the most abundant LC3
      isoform, did not inhibit but rather augmented virus production. Similar
      augmenting effects were obtained upon overexpression of a dominant negative
      mutant of Atg4B that blocked the lipid conjugation of the LC3 isoforms and their
      GABARAP paralogues. Together, our data indicate that HBV subverts early,
      nondegradative autophagy components as assembly scaffolds, thereby concurrently
      avoiding autophagosomal destruction.IMPORTANCE Infections with the hepatitis B
      virus (HBV), an enveloped pararetrovirus, cause about 1 million deaths per year,
      as current therapies rarely achieve a cure. Understanding the HBV life cycle and
      concomitant host cell interactions is instrumental to develop new antiviral
      concepts. Here, we proceeded to dissect the roles of the autophagy machinery in
      virus propagation. By using RNA interference and overexpression studies in HBV
      replicating cell lines, we identified the autophagic Atg5-12/16L1 elongation
      complex along with Atg10 and Atg3 to be an essential scaffold for HBV
      nucleocapsid assembly/stability. Deficits in Atg5-12/16L1 and Atg10/Atg3, which
      normally drive autophagophore membrane expansion, strongly impaired progeny virus
      yields. HBV gained access to Atg5-12/16L1 via interaction of its core protein
      with the Atg12 moiety of the complex. In contrast, subsequent autophagosome
      maturation and closure events were unnecessary for HBV replication, as evidenced
      by inhibition of Atg8/LC3 conjugation. Interfering with the HBV/Atg12 cross talk
      may be a tool for virus control.

PMID- 29367245
TI  - Genetic Analysis of Serum-Derived Defective Hepatitis C Virus Genomes Revealed
      Novel Viral cis Elements for Virus Replication and Assembly.
AB  - Defective viral genomes (DVGs) of hepatitis C virus (HCV) exist, but their
      biological significances have not been thoroughly investigated. Here, we analyzed
      HCV DVGs circulating in patient sera that possess deletions in the structural
      protein-encoding region. About 30% of 41 HCV clinical isolates possess DVGs that
      originated from the full-length genome in the same patients. No correlation
      between DVGs, viremia, and alanine aminotransferase (ALT) levels was found.
      Sequencing analysis of DVGs revealed the existence of deletion hot spots, with
      upstream sites in E1 and downstream sites in E2 and NS2. Interestingly, the
      coding sequences for the core protein and the C-terminal protease domain of NS2
      were always intact in DVGs despite the fact that both proteins are dispensable
      for HCV genome replication. Mechanistic studies showed that transmembrane segment
      3 (TMS3) of NS2, located immediately upstream of its protease domain, was
      required for the cleavage of NS2-NS3 and the replication of DVGs. Moreover, we
      identified a highly conserved secondary structure (SL750) within the core domain
      2-coding region that is critical for HCV genome packaging. In summary, our
      analysis of serum-derived HCV DVGs revealed novel viral cis elements that play
      important roles in virus replication and assembly.IMPORTANCE HCV DVGs have been
      identified in vivo and in vitro, but their biogenesis and physiological
      significances remain elusive. In addition, a conventional packaging signal has
      not yet been identified on the HCV RNA genome, and mechanisms underlying the
      specificity in the encapsidation of the HCV genome into infectious particles
      remain to be uncovered. Here, we identified new viral cis elements critical for
      the HCV life cycle by determining genetic constraints that define the boundary of
      serum-derived HCV DVGs. We found that transmembrane segment 3 of NS2, located
      immediately upstream of its protease domain, was required for the cleavage of NS2
      NS3 and the replication of DVGs. We identified a highly conserved secondary
      structure (SL750) within the core-coding region that is critical for HCV genome
      packaging. In summary, our analysis of serum-derived HCV DVGs revealed previously
      unexpected novel cis elements critical for HCV replication and morphogenesis.

PMID- 29367246
TI  - Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2
      Dependent Protein Degradation.
AB  - APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer
      genomes, including those of cervical and head and neck cancers caused by human
      papillomavirus (HPV) infection. However, the driving forces that promote off
      target A3 activity remain mostly unclear. Here, we report a mechanism for the
      dramatic increase of A3A protein levels in HPV-positive keratinocytes. We show
      that expression of the viral protein E7 from high-risk HPVs, but not E7 from low
      risk HPVs, significantly prolongs the cellular half-life of A3A protein in human
      keratinocytes and HPV-positive cancer cell lines. We have mapped several residues
      within the cullin 2 (CUL2) binding motif of HPV16 E7 as being important for
      mediating A3A protein stabilization. Furthermore, we provide direct evidence that
      both A3A and HPV16 E7 interact with CUL2, suggesting that the E7-CUL2 complex
      formed during HPV infection may regulate A3A protein levels in the cell. Using an
      in vitro cytidine deaminase assay, we show that E7-stabilized A3A remains
      catalytically active. Taken together, our findings suggest that the HPV
      oncoprotein E7 dysregulates endogenous A3A protein levels and thus provides novel
      mechanistic insight into cellular triggers of A3 mutations in HPV-positive
      cancers.IMPORTANCE Human papillomavirus (HPV) is causally associated with over 5%
      of all human malignancies. Several recent studies have shown that a subset of
      cancers, including HPV-positive head and neck and cervical cancers, have distinct
      mutational signatures potentially caused by members of the APOBEC3 cytidine
      deaminase family. However, the mechanism that induces APOBEC3 activity in cancer
      cells is poorly understood. Here, we report that the HPV oncoprotein E7
      stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting
      ubiquitin-dependent protein degradation in a cullin-dependent manner.
      Interestingly, the HPV E7-stabilized A3A protein maintains its deaminase
      activity. These findings provide a new insight into cancer mutagenesis enhanced
      by virus-induced A3A protein stabilization.

PMID- 29367248
TI  - Purification of highly active alphavirus replication complexes demonstrates
      altered fractionation of multiple cellular membranes.
AB  - Positive-strand RNA viruses replicate their genomes in membrane-associated
      structures; alphaviruses and many other groups induce membrane invaginations
      called spherules. Here, we established a protocol to purify these membranous
      replication complexes (RCs) from cells infected with Semliki Forest virus (SFV).
      We isolated SFV spherules located on the plasma membrane and further purified
      them using two consecutive density gradients. This revealed that SFV infection
      strongly modifies cellular membranes. We removed soluble proteins, the Golgi and
      most of the mitochondria, but plasma membrane, endoplasmic reticulum (ER) and
      late endosome markers enriched in the membrane fraction that contained viral RNA
      synthesizing activity, replicase proteins and minus- and plus-strand RNA.
      Electron microscopy revealed that the purified membranes displayed spherule-like
      structures with a narrow neck. This membrane enrichment was specific to viral
      replication as such a distribution of membrane markers was only observed after
      infection. Besides the plasma membrane, SFV infection remodeled the ER, and the
      co-fractionation of the RC-carrying plasma membrane and ER suggests that SFV may
      recruit ER proteins or membrane to the site of replication. The purified RCs were
      highly active in synthesizing both genomic and subgenomic RNA. Detergent
      solubilization destroyed the replication activity demonstrating that the membrane
      association of the complex is essential. Most of the newly made RNA was in double
      stranded replicative molecules but the purified complexes also produced single
      stranded RNA as well as released newly made RNA. This indicates that the
      purification established here maintained the functionality of RCs and thus
      enables further structural and functional studies of active RCs.IMPORTANCE
      Similar to all positive-strand RNA viruses, the arthropod-borne alphaviruses
      induce membranous genome factories but little is known about the arrangement of
      viral replicase proteins and the presence of host proteins in these replication
      complexes. To improve our knowledge of alphavirus RNA-synthesizing complexes, we
      isolated and purified them from infected mammalian cells. Detection of viral RNA
      and in vitro replication assays revealed that these complexes are abundant and
      highly active when located on the plasma membrane. After multiple purification
      steps, they remain functional in synthesizing and releasing viral RNA. Besides
      the plasma membrane, markers for the endoplasmic reticulum and late endosomes
      enriched with the replication complexes demonstrating that alphavirus infection
      modified cellular membranes beyond inducing replication spherules on the plasma
      membrane. We have here developed a gentle purification method to obtain large
      quantities of highly active replication complexes, and similar methods can be
      applied to other positive-strand RNA viruses.

PMID- 29367247
TI  - Epstein-Barr Virus (EBV) Latent Protein EBNA3A Directly Targets and Silences the
      STK39 Gene in B Cells Infected by EBV.
AB  - Epstein-Barr virus (EBV) establishes latent infection in human B cells and is
      associated with a wide range of cancers. The EBV nuclear antigen 3 (EBNA3) family
      proteins are critical for B cell transformation and function as transcriptional
      regulators. It is well established that EBNA3A and EBNA3C cooperate in the
      regulation of cellular genes. Here, we demonstrate that the gene STK39 is
      repressed only by EBNA3A. This is the first example of a gene regulated only by
      EBNA3A in EBV-transformed lymphoblastoid cell lines (LCLs) without the help of
      EBNA3C. This was demonstrated using a variety of LCLs carrying either knockout,
      revertant, or conditional EBNA3 recombinants. Investigating the kinetics of
      EBNA3A-mediated changes in STK39 expression showed that STK39 becomes derepressed
      quickly after EBNA3A inactivation. This derepression is reversible as EBNA3A
      reactivation represses STK39 in the same cells expressing a conditional EBNA3A.
      STK39 is silenced shortly after primary B cell infection by EBV, and no STK39
      encoded protein (SPAK) is detected 3 weeks postinfection. Chromatin
      immunoprecipitation (ChIP) analysis indicates that EBNA3A directly binds to a
      regulatory region downstream of the STK39 transcription start site. For the first
      time, we demonstrated that the polycomb repressive complex 2 with the deposition
      of the repressive mark H3K27me3 is not only important for the maintenance of an
      EBNA3A target gene (STK39) but is also essential for the initial establishment of
      its silencing. Finally, we showed that DNA methyltransferases are involved in the
      EBNA3A-mediated repression of STK39IMPORTANCE EBV is well known for its ability
      to transform B lymphocytes to continuously proliferating lymphoblastoid cell
      lines. This is achieved in part by the reprogramming of cellular gene
      transcription by EBV transcription factors, including the EBNA3 proteins that
      play a crucial role in this process. In the present study, we found that EBNA3A
      epigenetically silences STK39 This is the first gene where EBNA3A has been found
      to exert its repressive role by itself, without needing its coregulators EBNA3B
      and EBNA3C. Furthermore, we demonstrated that the polycomb repressor complex is
      essential for EBNA3A-mediated repression of STK39 Findings in this study provide
      new insights into the regulation of cellular genes by the transcription factor
      EBNA3A.

PMID- 29367249
TI  - Defining the Barriers to Women Publishing in High-Impact Journals.
AB  - Publications are an important measure of success in science, and publications in
      top-tier journals are often highly prized for that reason. This commentary
      describes gender differences in publication of HIV-related papers that raise
      questions about best practices in this important aspect of science. Data are
      needed in cases where there are differences in the publication rates of
      manuscripts with female versus male senior authors so that approaches that best
      support diversity in science can be defined.

PMID- 29367251
TI  - MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell
      Activation in the Brain.
AB  - MALT1 is involved in the activation of immune responses, as well as in the
      proliferation and survival of certain cancer cells. MALT1 acts as a scaffold
      protein for NF-kappaB signaling and a cysteine protease that cleaves substrates,
      further promoting the expression of immunoregulatory genes. Deregulated MALT1
      activity has been associated with autoimmunity and cancer, implicating MALT1 as a
      new therapeutic target. Although MALT1 deficiency has been shown to protect
      against experimental autoimmune encephalomyelitis, nothing is known about the
      impact of MALT1 on virus infection in the central nervous system. Here, we
      studied infection with an attenuated rabies virus, Evelyn-Rotnycki-Abelseth (ERA)
      virus, and observed increased susceptibility with ERA virus in MALT1-/- mice.
      Indeed, after intranasal infection with ERA virus, wild-type mice developed mild
      transient clinical signs with recovery at 35 days postinoculation (dpi).
      Interestingly, MALT1-/- mice developed severe disease requiring euthanasia at
      around 17 dpi. A decreased induction of inflammatory gene expression and cell
      infiltration and activation was observed in MALT1-/- mice at 10 dpi compared to
      MALT1+/+ infected mice. At 17 dpi, however, the level of inflammatory cell
      activation was comparable to that observed in MALT1+/+ mice. Moreover, MALT1-/-
      mice failed to produce virus-neutralizing antibodies. Similar results were
      obtained with specific inactivation of MALT1 in T cells. Finally, treatment of
      wild-type mice with mepazine, a MALT1 protease inhibitor, also led to mortality
      upon ERA virus infection. These data emphasize the importance of early
      inflammation and activation of T cells through MALT1 for controlling the
      virulence of an attenuated rabies virus in the brain.IMPORTANCE Rabies virus is a
      neurotropic virus which can infect any mammal. Annually, 59,000 people die from
      rabies. Effective therapy is lacking and hampered by gaps in the understanding of
      virus pathogenicity. MALT1 is an intracellular protein involved in innate and
      adaptive immunity and is an interesting therapeutic target because MALT1
      deregulated activity has been associated with autoimmunity and cancers. The role
      of MALT1 in viral infection is, however, largely unknown. Here, we study the
      impact of MALT1 on virus infection in the brain, using the attenuated ERA rabies
      virus in different models of MALT1-deficient mice. We reveal the importance of
      MALT1-mediated inflammation and T cell activation to control ERA virus, providing
      new insights in the biology of MALT1 and rabies virus infection.

PMID- 29367250
TI  - Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41
      Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells.
AB  - Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The
      main characteristics of HAdV-41 infection are diarrhea and vomiting.
      Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a
      suitable small-animal model has not been described. In this study, we used the
      human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41
      infection and the individual HAdV-41 capsid proteins on serotonin release by
      enterochromaffin cells and on enteric glia cell (EGC) activation. We first
      determined that HAdV-41 could infect the enterochromaffin cells.
      Immunofluorescence staining revealed that the cells expressed HAdV-41-specific
      coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported
      these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin
      secretion dose dependently. In contrast, control infection with HAdV-5 did not
      induce serotonin secretion in the cells. Confocal microscopy studies of
      enterochromaffin cells infected with HAdV-41 revealed decreased serotonin
      immunofluorescence compared to that in uninfected cells. Incubation of the
      enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins
      increased the serotonin levels in the harvested cell supernatant significantly.
      HAdV-41 infection could also activate EGCs, as shown in the significantly altered
      expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV
      41. The EGCs were also activated by serotonin alone, as shown in the
      significantly increased GFAP staining intensity. Likewise, EGCs were activated by
      the cell supernatant of HAdV-41-infected enterochromaffin cells.IMPORTANCE The
      nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low
      grade fever mainly in children under 2 years of age. Even though acute
      gastroenteritis is well described, how human adenovirus 41 causes diarrhea is
      unknown. In our study, we analyzed the effect of human adenovirus 41 infection on
      human enterochromaffin cells and found it stimulates serotonin secretion in the
      cells, which is involved in regulation of intestinal secretion and gut motility
      and can also activate enteric glia cells, which are found in close proximity to
      enterochromaffin cells in vivo This disruption of gut barrier homeostasis as
      maintained by these cells following human adenovirus 41 infection might be a
      mechanism in enteric adenovirus pathogenesis in humans and could indicate a
      possible serotonin-dependent cross talk between human adenovirus 41,
      enterochromaffin cells, and enteric glia cells.

PMID- 29367254
TI  - Receptor signaling and neutral endopeptidase are involved in the resistance of C
      type natriuretic peptide to human mesangial proliferation and collagen-IV
      expression.
AB  - C-type natriuretic peptide (CNP) is regarded as a local, paracrine hormone to
      regulate vascular tone and cell proliferation. Although several in vivo studies
      have documented that CNP exerts the inhibitory effects on mesangial cells (MCs)
      proliferation and collagen production, a limited number of studies exist about
      the resistance of CNP to MCs proliferation in vitro. Besides, whether its
      receptor signaling and neutral endopeptidase (NEP) are involved remains unclear.
      In the present study, human MCs were incubated in serum-containing medium in the
      absence or presence of CNP (0, 10 and 100 pM) for 24, 48 and 72 hours,
      respectively. CNP administration significantly suppresses MCs proliferation and
      collagen-IV (Col-IV) expression in a time-dependent and dose-dependent manner. As
      a down-stream signal molecule of CNP activation, the expressions of natriuretic
      peptide receptor (NPR)-B, cyclic guanosine monophosphate-dependent protein
      kinases II and NPR-C were obviously augmented, whereas NEP expression was
      significantly decreased after CNP treatment. In conclusion, receptor signaling
      and NEP are involved in the resistance of CNP to human mesangial proliferation
      and Col-IV expression.

PMID- 29367252
TI  - Mimicry of Cellular A Kinase-Anchoring Proteins Is a Conserved and Critical
      Function of E1A across Various Human Adenovirus Species.
AB  - The E1A proteins of the various human adenovirus (HAdV) species perform the
      critical task of converting an infected cell into a setting primed for virus
      replication. While E1A proteins differ in both sequence and mechanism, the
      evolutionary pressure on viruses with limited coding capacity ensures that these
      proteins often have significant overlap in critical functions. HAdV-5 E1A is
      known to use mimicry to rewire cyclic AMP (cAMP) signaling by decoupling protein
      kinase A (PKA) from cellular A kinase-anchoring proteins (AKAPs) and utilizing
      PKA to its own advantage. We show here that E1As from other species of HAdV also
      possess this viral AKAP (vAKAP) function and examine how they manipulate PKA. E1A
      from most species of HAdV examined contain a small AKAP-like motif in their N
      terminus which targets the docking-dimerization domain of PKA as the binding
      interface for a conserved protein-protein interaction. This motif is also
      responsible for an E1A-mediated relocalization of PKA regulatory subunits from
      the cytoplasm into the nucleus, with species-specific E1A proteins having
      preference for one particular isoform of PKA subunit over another. Importantly,
      we showed that these newly characterized vAKAPs can integrate into cAMP
      responsive transcription as well as contribute to viral genome replication and
      infectious progeny production for several distinct HAdV species.IMPORTANCE These
      data enhance the mechanistic knowledge on how HAdV E1A manipulates cellular PKA
      to benefit infection. The work establishes that mimicry of AKAPs and subversion
      of PKA-mediated cAMP signaling are conserved features for numerous human
      adenoviruses. This study also highlights the molecular determinants conferring
      selective protein-protein interactions between distinct PKA regulatory subunits
      and the different E1A proteins of these viruses. Additionally, it further
      emphasizes the utility of using viral proteins like E1A as tools for studying the
      molecular biology of cellular regulatory pathways.

PMID- 29367253
TI  - Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites
      Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP
      A/B, and SAC1.
AB  - Positive-strand RNA viruses, including picornaviruses, utilize cellular machinery
      for genome replication. Previously, we reported that each of the 2B, 2BC, 2C, 3A,
      and 3AB proteins of Aichi virus (AiV), a picornavirus, forms a complex with the
      Golgi apparatus protein ACBD3 and phosphatidylinositol 4-kinase IIIbeta (PI4KB)
      at viral RNA replication sites (replication organelles [ROs]), enhancing PI4KB
      dependent phosphatidylinositol 4-phosphate (PI4P) production. Here, we
      demonstrate AiV hijacking of the cellular cholesterol transport system involving
      oxysterol-binding protein (OSBP), a PI4P-binding cholesterol transfer protein.
      AiV RNA replication was inhibited by silencing cellular proteins known to be
      components of this pathway, OSBP, the ER membrane proteins VAPA and VAPB (VAP
      A/B), the PI4P-phosphatase SAC1, and PI-transfer protein beta. OSBP, VAP-A/B, and
      SAC1 were present at RNA replication sites. We also found various previously
      unknown interactions among the AiV proteins (2B, 2BC, 2C, 3A, and 3AB), ACBD3,
      OSBP, VAP-A/B, and SAC1, and the interactions were suggested to be involved in
      recruiting the component proteins to AiV ROs. Importantly, the OSBP-2B
      interaction enabled PI4P-independent recruitment of OSBP to AiV ROs, indicating
      preferential recruitment of OSBP among PI4P-binding proteins. Protein-protein
      interaction-based OSBP recruitment has not been reported for other
      picornaviruses. Cholesterol was accumulated at AiV ROs, and inhibition of OSBP
      mediated cholesterol transfer impaired cholesterol accumulation and AiV RNA
      replication. Electron microscopy showed that AiV-induced vesicle-like structures
      were close to ER membranes. Altogether, we conclude that AiV directly recruits
      the cholesterol transport machinery through protein-protein interactions,
      resulting in formation of membrane contact sites between the ER and AiV ROs and
      cholesterol supply to the ROs.IMPORTANCE Positive-strand RNA viruses utilize host
      pathways to modulate the lipid composition of viral RNA replication sites for
      replication. Previously, we demonstrated that Aichi virus (AiV), a picornavirus,
      forms a complex comprising certain proteins of AiV, the Golgi apparatus protein
      ACBD3, and the lipid kinase PI4KB to synthesize PI4P lipid at the sites for AiV
      RNA replication. Here, we confirmed cholesterol accumulation at the AiV RNA
      replication sites, which are established by hijacking the host cholesterol
      transfer machinery mediated by a PI4P-binding cholesterol transfer protein, OSBP.
      We showed that the component proteins of the machinery, OSBP, VAP, SAC1, and
      PITPNB, are all essential host factors for AiV replication. Importantly, the
      machinery is directly recruited to the RNA replication sites through previously
      unknown interactions of VAP/OSBP/SAC1 with the AiV proteins and with ACBD3.
      Consequently, we propose a specific strategy employed by AiV to efficiently
      accumulate cholesterol at the RNA replication sites via protein-protein
      interactions.

PMID- 29367256
TI  - Drug shortages derail CCGs' budgets.

PMID- 29367255
TI  - Hydration and obesity among outpatient-based population: H2Ob study.
AB  - Recent evidence suggests that obese people are hypohydrated and that water
      consumption may be a useful indicator for the prevention and treatment of
      obesity. Nevertheless, there is no agreement regarding the best hydration status
      indicators and there are few data about the relationship between hydration and
      body weight. In the present study, we aim to analyze the correlation among
      hydration status with obesity measured by three different methods (plasma
      osmolarity, urinary specific gravity (USG) and urinary osmolarity) in a hospital
      based outpatient population. We have carried out a cross-sectional study to
      evaluate the association between obesity and hydration status in 260 patients,
      average 56.5+/-15.7 years. Hydration status was estimated by means of plasma
      osmolarity, urine osmolarity and USG. We did show significant trend of higher
      urine osmolarity (P=0.03), USG (P=0.000) and plasma osmolarity (P=0.000) with an
      increase of weight status categories, more accurate in the case of plasma
      osmolarity. In a multivariate analysis, after controlled by confounders, we found
      that obesity was associated with plasma osmolarity (OR 1.09; 95% CI 1.02 to 1.17,
      P=0.009), urine osmolarity (OR 1.00; 95% CI 1.00 to 1.01, P=0.05) and USG (OR
      1.02; 95% CI 1.00 to 1.04, P=0.05). Our results have shown a more accurate
      relationship between plasma osmolarity with all body mass index categories. This
      finding may have clinical implications that must be confirmed in further studies.

PMID- 29367257
TI  - Elucidation of the Binding Mode of the Carboxyterminal Region of Peptide YY to
      the Human Y2 Receptor.
AB  - Understanding the agonist-receptor interactions in the neuropeptide Y
      (NPY)/peptide YY (PYY) signaling system is fundamental for the design of novel
      modulators of appetite regulation. We report here the results of a
      multidisciplinary approach to elucidate the binding mode of the native peptide
      agonist PYY to the human Y2 receptor, based on computational modeling, peptide
      chemistry and in vitro pharmacological analyses. The preserved binding
      orientation proposed for full-length PYY and five analogs, truncated at the amino
      terminus, explains our pharmacological results where truncations of the N
      terminal proline helix showed little effect on peptide affinity. This was
      followed by receptor mutagenesis to investigate the roles of several receptor
      positions suggested by the modeling. As a complement, PYY-(3-36) analogs were
      synthesized with modifications at different positions in the common PYY/NPY C
      terminal fragment (32TRQRY36-amide). The results were assessed and interpreted by
      molecular dynamics and Free Energy Perturbation (FEP) simulations of selected
      mutants, providing a detailed map of the interactions of the PYY/NPY C-terminal
      fragment with the transmembrane cavity of the Y2 receptor. The amidated C
      terminus would be stabilized by polar interactions with Gln2886.55 and
      Tyr2195.39, while Gln1303.32 contributes to interactions with Q34 in the peptide
      and T32 is close to the tip of TM7 in the receptor. This leaves the core, alpha
      helix of the peptide exposed to make potential interactions with the
      extracellular loops. This model agrees with most experimental data available for
      the Y2 system and can be used as a basis for optimization of Y2 receptor
      agonists.

PMID- 29367258
TI  - Identifying Functional Hotspot Residues for Biased Ligand Design in G-Protein
      Coupled Receptors.
AB  - G-protein-coupled receptors (GPCRs) mediate multiple signaling pathways in the
      cell, depending on the agonist that activates the receptor and multiple cellular
      factors. Agonists that show higher potency to specific signaling pathways over
      others are known as "biased agonists" and have been shown to have better
      therapeutic index. Although biased agonists are desirable, their design poses
      several challenges to date. The number of assays to identify biased agonists
      seems expensive and tedious. Therefore, computational methods that can reliably
      calculate the possible bias of various ligands ahead of experiments and provide
      guidance, will be both cost and time effective. In this work, using the mechanism
      of allosteric communication from the extracellular region to the intracellular
      transducer protein coupling region in GPCRs, we have developed a computational
      method to calculate ligand bias ahead of experiments. We have validated the
      method for several beta-arrestin-biased agonists in beta2-adrenergic receptor
      (beta2AR), serotonin receptors 5-HT1B and 5-HT2B and for G-protein-biased
      agonists in the kappa-opioid receptor. Using this computational method, we also
      performed a blind prediction followed by experimental testing and showed that the
      agonist carmoterol is beta-arrestin-biased in beta2AR. Additionally, we have
      identified amino acid residues in the biased agonist binding site in both beta2AR
      and kappa-opioid receptors that are involved in potentiating the ligand bias. We
      call these residues functional hotspots, and they can be used to derive
      pharmacophores to design biased agonists in GPCRs.

PMID- 29367260
TI  - Sequencing analysis of the SCA6 CAG expansion excludes an influence of repeat
      interruptions on disease onset.

PMID- 29367259
TI  - Pharmacogenomics of Chemically Distinct Classes of Keap1-Nrf2 Activators Identify
      Common and Unique Gene, Protein, and Pathway Responses In Vivo.
AB  - The Kelch-like erythroid-associated protein 1 (Keap1)-NF-E2-related factor 2
      (Nrf2) signaling pathway is the subject of several clinical trials evaluating the
      effects of Nrf2 activation on the prevention of cancer and diabetes and the
      treatment of chronic kidney disease and multiple sclerosis. 3H-1,2-dithiole-3
      thione (D3T) and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO
      Im) are representative members of two distinct series of Nrf2 chemical
      activators. Previous reports have described activator-specific effects on Nrf2
      dependent gene regulation and physiologic outcomes. Here we used a robust
      chemical genomics approach to characterize expression profiles between D3T and
      CDDO-Im in livers from wild-type and Nrf2-null mice. At equally efficacious doses
      in wild-type mice, 406 genes show common RNA responses to both treatments. These
      genes enriched the Nrf2-regulated pathways of antioxidant defense and xenobiotic
      metabolism. In addition, 197 and 745 genes were regulated uniquely in response to
      either D3T or CDDO-Im, respectively. Functional analysis of the D3T-regulated set
      showed a significant enrichment of Nrf2-regulated enzymes involved in cholesterol
      biosynthesis. This result was supported by Nrf2-dependent increases in lanosterol
      synthase and CYP51 protein expression. CDDO-Im had no effect on cholesterol
      biosynthesis regardless of the dose tested. However, unlike D3T, CDDO-Im resulted
      in Nrf2-dependent elevation of peroxisome proliferator alpha and Kruppel-like
      factor 13, as well as the coactivator peroxisome proliferator gamma coactivator
      1beta, together indicating regulation of beta-oxidation and lipid metabolic
      pathways. These findings provide novel insights into the pharmacodynamic action
      of these two activators of Keap1-Nrf2 signaling. Although both compounds modify
      Keap1 to affect canonical cytoprotective gene expression, additional unique sets
      of Nrf2-dependent genes were regulated by each agent with enrichment of selective
      metabolic pathways.

PMID- 29367261
TI  - Recreational nitrous oxide-associated neurotoxicity.

PMID- 29367262
TI  - Early deaths from ischaemic heart disease in childhood-onset type 1 diabetes.
AB  - AIMS: The risk of ischaemic heart disease (IHD) death in early type 1 diabetes
      onset was assessed using death certification data. METHODS: The Yorkshire
      Register of type 1 Diabetes in Children and Young People was linked to clinically
      validated death certification data for those diagnosed under 15 years.
      Standardised mortality ratios (SMRs) were calculated using the England and Wales
      population and IHD death rates between 1978 and 2014 by 5-year age group and sex.
      RESULTS: The cohort included 4382 individuals (83a?0/00097 person years). Of 156
      deaths, nine were classed as IHD deaths before clinical validation. After
      clinical validation, 14 IHD deaths were classified, with an SMR of 13.8 (95% CI
      8.2 to 23.3) and median age at death of 35.1 years (range 21.9a?"47.9 years).
      CONCLUSIONS: There is an early emergence of death from IHD in early onset type 1
      diabetes. Underascertainment of IHD deaths was present without clinical
      validation of death certification.

PMID- 29367264
TI  - Cannabis use among middle and high school students in Ontario: a school-based
      cross-sectional study.
AB  - BACKGROUND: Cannabis use can have serious detrimental effects in children and
      adolescents. It is therefore important to continually assess the use of cannabis
      among young people in order to inform prevention efforts. We assessed the
      prevalence of cannabis use among middle and high school students in Ontario and
      examined its association with demographic and behavioural factors. METHODS: Data
      were obtained from the 2015 Ontario Student Drug Use and Health Survey, a
      province-wide school-based survey of students in grades 7 through 12. Analyses
      included a representative sample of 9920 middle and high school students.
      Bivariate cross-tabulations and logistic regression analyses were used to
      investigate the factors associated with cannabis use. RESULTS: Overall, 21.5% and
      13.9% of students reported using cannabis in the previous year and previous
      month, respectively. The conditional probability that an adolescent who reported
      cannabis use in the previous year would report daily use was 12.5%. There was a
      significant dose-response gradient with age, with older students being more
      likely to use cannabis than younger students. In multivariable analyses, being in
      grades 10 through 12 (odds ratios [ORs] ranged from 3.71 to 3.85), being black
      (OR 2.67 [95% confidence interval (CI) 1.76-4.05]), using tobacco cigarettes (OR
      10.10 [95% CI 8.68-13.92]) and being an occasional (OR 5.35 [95% CI 4.01-7.13])
      or regular (OR 14.6 [95% CI 10.8-19.89]) alcohol user were associated with
      greater odds of cannabis use. Being an immigrant was associated with lower odds
      of cannabis use (OR 0.55 [95% CI 0.39-0.78]). INTERPRETATION: The findings
      suggest that cannabis use is prevalent among middle and high school students in
      Ontario and is strongly associated with tobacco cigarette smoking and alcohol
      consumption. Future research should document trends in cannabis use over time,
      including its risks, especially when the legalization of recreational cannabis
      comes into effect.

PMID- 29367266
TI  - The Novel Oncolytic Adenoviral Mutant Ad5-3Delta-A20T Retargeted to alphavbeta6
      Integrins Efficiently Eliminates Pancreatic Cancer Cells.
AB  - Metastatic pancreatic ductal adenocarcinomas (PDAC) are incurable due to the
      rapid development of resistance to all current therapeutics. Oncolytic adenoviral
      mutants have emerged as a promising new strategy that negates such resistance. In
      contrast to normal tissue, the majority of PDACs express the alphavbeta6 integrin
      receptor. To exploit this feature, we modified our previously reported oncolytic
      adenovirus, AdDeltaDelta, to selectively target alphavbeta6 integrins to
      facilitate systemic delivery. Structural modifications to AdDeltaDelta include
      the expression of the small but potent alphavbeta6-binding peptide, A20FMDV2, and
      ablation of binding to the native coxsackie and adenovirus receptor (CAR) within
      the fiber knob region. The resultant mutant, Ad5-3Delta-A20T, infected and killed
      alphavbeta6 integrin-expressing cells more effectively than the parental wild
      type (Ad5wt) virus and AdDeltaDelta. Viral uptake through alphavbeta6 integrins
      rather than native viral receptors (CAR, alphavbeta3 and alphavbeta5 integrins)
      promoted viral propagation and spread. Superior efficacy of Ad5-3Delta-A20T
      compared with Ad5wt was demonstrated in 3D organotypic cocultures, and similar
      potency between the two viruses was observed in Suit-2 in vivo models.
      Importantly, Ad5-3Delta-A20T infected pancreatic stellate cells at low levels,
      which may further facilitate viral spread and cancer cell elimination either as a
      single agent or in combination with the chemotherapy drug, gemcitabine. We
      demonstrate that Ad5-3Delta-A20T is highly selective for alphavbeta6 integrin
      expressing pancreatic cancer cells, and with further development, this new and
      exciting strategy can potentially be extended to improve the systemic delivery of
      adenoviruses to pancreatic cancer patients. Mol Cancer Ther; 17(2); 575-87.
      (c)2018 AACR.

PMID- 29367265
TI  - Crystal structure of thermospermine synthase from Medicago truncatula and
      substrate discriminatory features of plant aminopropyltransferases.
AB  - Polyamines are linear polycationic compounds that play a crucial role in the
      growth and development of higher plants. One triamine (spermidine, SPD) and two
      tetraamine isomers (spermine, SPM, and thermospermine, TSPM) are obtained by the
      transfer of the aminopropyl group from decarboxylated S-adenosylmethionine to
      putrescine and SPD. These reactions are catalyzed by the specialized
      aminopropyltransferases. In that respect, plants are unique eukaryotes that have
      independently evolved two enzymes, thermospermine synthase (TSPS), encoded by the
      gene ACAULIS5, and spermine synthase, which produce TSPM and SPM, respectively.
      In this work, we structurally characterize the ACAULIS5 gene product, TSPS, from
      the model legume plant Medicago truncatula (Mt). Six crystal structures of MtTSPS
      - one without ligands and five in complexes with either reaction substrate (SPD),
      reaction product (TSPM), or one of three cofactor analogs (5'
      methylthioadenosine, S-adenosylthiopropylamine, and adenosine) - give detailed
      insights into the biosynthesis of TSPM. Combined with small-angle X-ray
      scattering data, the crystal structures show that MtTSPS is a symmetric
      homotetramer with an interdomain eight-stranded beta-barrel. Such an assembly and
      the presence of a hinge-like feature between N-terminal and C-terminal domains
      give the protein additional flexibility which potentially improves loading
      substrates and discarding products after the catalytic event. We also discuss the
      sequence and structural features around the active site of the plant
      aminopropyltransferases that distinguish them from each other and determine their
      characteristic substrate discrimination.

PMID- 29367267
TI  - Doctors are cleared to prescribe cheaper drug for wet AMD.

PMID- 29367268
TI  - Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia
      in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure):
      Clinical and Prognostic Associations.
AB  - BACKGROUND: A poor response to erythropoiesis-stimulating agents such as
      darbepoetin alfa has been associated with adverse outcomes in patients with
      diabetes mellitus, chronic kidney disease, and anemia; whether this is also true
      in heart failure is unclear. METHODS AND RESULTS: We performed a post hoc
      analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart
      Failure), in which 1008 patients with systolic heart failure and anemia
      (hemoglobin level, 9.0-12.0 g/dL) were randomized to darbepoetin alfa. We
      examined the relationship between the hematopoietic response to darbepoetin alfa
      and the incidence of all-cause death or first heart failure hospitalization
      during a follow-up of 28 months. For the purposes of the present study, patients
      in the lowest quartile of hemoglobin change after 4 weeks were considered
      nonresponders. The median initial hemoglobin change in nonresponders (n=252) was 
      0.25 g/dL and +1.00 g/dL in the remainder of patients (n=756). Worse renal
      function, lower sodium levels, and less use of angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers were independently associated with
      nonresponse. Although a low endogenous erythropoietin level helped to
      differentiate responders from nonresponders, its predictive value in a
      multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate
      of all-cause death or first heart failure hospitalization (hazard ratio, 1.25;
      95% confidence interval, 1.02-1.54) and a higher risk of all-cause mortality
      (hazard ratio, 1.30; 95% confidence interval, 1.04-1.63) than responders.
      CONCLUSIONS: A poor response to darbepoetin alfa was associated with worse
      outcomes in heart failure patients with anemia. Patients with a poor response
      were difficult to identify using clinical and biochemical biomarkers. CLINICAL
      TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT00358215.

PMID- 29367269
TI  - Percutaneous Occlusion of Patent Ductus Arteriosus for an Elderly Patient With
      Refractory Congestive Heart Failure.

PMID- 29367270
TI  - The BMJ charity appeal Christmas 2017: help Medecins Sans Frontieres help child
      refugees worldwide.

PMID- 29367271
TI  - Functional plasticity of the gut and the Malpighian tubules underlies cold
      acclimation and mitigates cold-induced hyperkalemia in Drosophila melanogaster.
AB  - At low temperatures, Drosophila, like most insects, lose the ability to regulate
      ion and water balance across the gut epithelia, which can lead to a lethal
      increase of [K+] in the hemolymph (hyperkalemia). Cold acclimation, the
      physiological response to a prior low temperature exposure, can mitigate or
      entirely prevent these ion imbalances, but the physiological mechanisms that
      facilitate this process are not well understood. Here, we test whether plasticity
      in the ionoregulatory physiology of the gut and Malpighian tubules of Drosophila
      may aid in preserving ion homeostasis in the cold. Upon adult emergence, D.
      melanogaster females were subjected to 7 days at warm (25 degrees C) or cold (10
      degrees C) acclimation conditions. The cold-acclimated flies had a lower critical
      thermal minimum (CTmin), recovered from chill coma more quickly, and better
      maintained hemolymph K+ balance in the cold. The improvements in chill tolerance
      coincided with increased Malpighian tubule fluid secretion and better maintenance
      of K+ secretion rates in the cold, as well as reduced rectal K+ reabsorption in
      cold-acclimated flies. To test whether modulation of ion-motive ATPases, the main
      drivers of epithelial transport in the alimentary canal, mediate these changes,
      we measured the activities of Na+/K+-ATPase and V-type H+-ATPase at the
      Malpighian tubules, midgut, and hindgut. Na+/K+-ATPase and V-type H+-ATPase
      activities were lower in the midgut and the Malpighian tubules of cold-acclimated
      flies, but unchanged in the hindgut of cold-acclimated flies, and were not
      predictive of the observed alterations in K+ transport. Our results suggest that
      modification of Malpighian tubule and gut ion and water transport probably
      prevents cold-induced hyperkalemia in cold-acclimated flies, and that this
      process is not directly related to the activities of the main drivers of ion
      transport in these organs, Na+/K+- and V-type H+-ATPases.

PMID- 29367272
TI  - Hormetic benefits of prior anoxia exposure in buffering anoxia stress in a soil
      pupating insect.
AB  - Oxygen is essential for most animals, and exposure to a complete lack of oxygen,
      i.e. anoxia, can result in irreparable damage to cells that can extend up to the
      organismal level to negatively affect performance. Although it is known that
      brief anoxia exposure may confer cross-tolerance to other stressors, few data
      exist on the biochemical and organismal consequences of repeated intermittent
      bouts of anoxia exposure. In nature, the Caribbean fruit fly, Anastrepha suspensa
      (Diptera: Tephritidae), is frequently exposed to heavy tropical rainfall while
      pupating in the soil, equating to multiple exposures to hypoxia or anoxia during
      development. Here, we tested whether prior anoxia exposures during pupal
      development can induce a beneficial acclimation response, and we explored the
      consequences of prior exposure for both whole-organism performance and correlated
      biochemical metrics. Pharate adults (the last developmental stage in the pupal
      case) were most sensitive to anoxia exposure, showing decreased survival and
      fertility compared with controls. These negative impacts were ameliorated by
      exposure to anoxia in earlier pupal developmental stages, indicating a hormetic
      effect of prior anoxia exposure. Anoxia exposure early in pupal development
      reduced the oxygen debt repaid after anoxia exposure relative to pharate adults
      experiencing anoxia for the first time. Lipid levels were highest in all pupal
      stages when exposed to prior anoxia. Prior anoxia thus benefits organismal
      performance and relocates resources towards lipid storage throughout pupal-adult
      development.

PMID- 29367273
TI  - Through the eye of a lizard: hue discrimination in a lizard with ventral
      polymorphic coloration.
AB  - Colour polymorphisms are thought to be maintained by complex evolutionary
      processes, some of which require that the colours of the alternative morphs
      function as chromatic signals to conspecifics. Unfortunately, a key aspect of
      this hypothesis has rarely been studied: whether the study species perceives its
      own colour variation as discrete rather than continuous. The European common wall
      lizard (Podarcis muralis) presents a striking colour polymorphism: the ventral
      surface of adults of both sexes may be coloured orange, white, yellow or with a
      mosaic of scales combining two colours (orange-white, orange-yellow). Here, we
      used a discrimination learning paradigm to test whether P. muralis is capable of
      discriminating colour stimuli designed to match the ventral colours of
      conspecifics. We trained 20 lizards to eat from colour-coded wells bored in
      wooden blocks. Blocks had four colour-coded wells (orange, white, yellow and an
      achromatic control), but only one contained food (mealworm larvae). After six
      trials, the lizards performed significantly better than expected by chance,
      showing a decrease in both the number of wells explored and the latency to
      finding the food. Using visual modelling techniques, we found that, based on
      their spectral properties and the lizards' cone sensitivities, the ventral
      colours of P. muralis correspond to discrete rather than continuous colour
      categories, and that colour discriminability (i.e. distance in perceptual space)
      varies depending on the morphs compared, which may have implications for signal
      detection and discrimination. These results suggest that P. muralis can
      discriminate hue differences matching their own ventral colour variation.

PMID- 29367275
TI  - Vibration-guided mate searching in treehoppers: directional accuracy and sampling
      strategies in a complex sensory environment.
AB  - Animal movement decisions involve an action-perception cycle in which sensory
      flow influences motor output. Key aspects of the action-perception cycle involved
      in movement decisions can be identified by integrating path information with
      measurement of environmental cues. We studied mate searching in insects for which
      the primary sensory cues are mechanical vibrations traveling through the tissues
      of living plants. We mapped search paths of male thornbug treehoppers locating
      stationary females through an exchange of vibrational signals. At each of the
      males' sampling locations, we used two-dimensional laser vibrometry to measure
      stem motion produced by female vibrational signals. We related properties of the
      vibrational signals to the males' movement direction, inter-sample distance and
      accuracy. Males experienced gradients in signal amplitude and in the whirling
      motion of the plant stem, and these gradients were influenced to varying degrees
      by source distance and local stem properties. Males changed their sampling
      behavior during the search, making longer inter-sample movements farther from the
      source, where uncertainty is higher. The primary directional cue used by
      searching males was the direction of wave propagation, and males made more
      accurate decisions when signal amplitude was higher, when time delays were longer
      between the front and back legs, and when female responses were short in
      duration. The whirling motion of plant stems, including both the eccentricity and
      the major axes of motion, is a fundamental feature of vibrational environments on
      living plants, and we show for the first time that it has important influences on
      the decisions of vibrationally homing insects.

PMID- 29367276
TI  - Regulation of UDP-Glucuronosyltransferase 2B15 by miR-331-5p in Prostate Cancer
      Cells Involves Canonical and Noncanonical Target Sites.
AB  - UGT2B15 is an important androgen-metabolizing UDP-glucuronosyltransferase (UGT)
      and the mechanisms controlling its expression are of considerable interest.
      Recent studies showed that miR-376c regulates UGT2B15 in prostate cancer cells
      via a canonical target site in the 3' untranslated region (3'UTR). The UGT2B15
      3'UTR also contains a canonical miR-331-5p target site; previous work indicated
      that deleting this site reduced, but did not abolish, the ability of miR-331-5p
      to repress a luciferase reporter carrying the UGT2B15 3'UTR We report here the
      discovery and characterization of a second, noncanonical miR-331-5p target site
      in the UGT2B15 3'UTR miR-331-5p-mediated repression of a UGT2B15 3'UTR-reporter
      was partly inhibited by mutating either of the two miR-331-5p target sites
      separately, but completely abolished by mutating the two sites simultaneously,
      indicating that the two sites act cooperatively. miR-331-5p mimics significantly
      reduced both UGT2B15 mRNA levels and glucuronidation activity in prostate cancer
      cells, confirming that the native transcript is a miR-331-5p target. Transfection
      of either miR-331-5p or miR-376c mimics repressed the activity of the UGT2B15
      3'UTR-reporter; however, cotransfection of both microRNAs (miRNAs) further
      reduced activity, indicating cooperative regulation by these two miRNAs. A
      significant negative correlation between miR-331 and UGT2B15 mRNA levels was
      observed in a tissue RNA panel, and analysis of The Cancer Genome Atlas (TCGA)
      hepatocellular carcinoma data set provided further evidence that miR-331 may play
      an important role in regulation of UGT2B15 in vivo. There was no significant
      correlation between miR-331 and UGT2B15 mRNA levels in the TCGA prostate
      adenocarcinoma cohort, which may reflect the complexity of androgen-mediated
      regulation in determining UGT2B15 levels in prostate cancer. Finally, we show
      that miR-331-5p does not regulate UGT2B17, providing the first evidence for a
      post-transcriptional mechanism that differentially regulates these two important
      androgen-metabolizing UGTs.

PMID- 29367277
TI  - Targeting Glycine Reuptake in Alcohol Seeking and Relapse.
AB  - It has recently been demonstrated that pharmacological blockade of the glycine
      transporter 1 (GlyT1) reduced alcohol intake and relapse in rats. The aim of the
      present study was to further explore the role of GlyT1 in alcohol relapse-like
      behavior. For this purpose we used three different GlyT1 blockers-SSR504734, A
      1246399, and RO4993850-and tested their effect on alcohol-seeking and relapse
      like consumption. Two behavioral models, the alcohol deprivation effect model and
      the cue-induced reinstatement model, were used. Our data show that all three
      GlyT1 blockers reduce relapse-like alcohol consumption and cause either minimal
      or no side effects, measured as changes in home-cage activity, water intake, and
      body weight. In the reinstatement test, GlyT1 blockers completely abolished
      alcohol-seeking responses. Furthermore, we tested other drug/cue associations and
      found that cocaine-seeking responses were also abolished by GlyT1 blockade. Our
      data confirm that GlyT1 can be used as a target to develop novel anticraving and
      antirelapse drugs.

PMID- 29367279
TI  - NHS care has worsened over the past year, doctors warn.

PMID- 29367278
TI  - "No deal" Brexit would threaten access to new drugs, Hunt warns.

PMID- 29367274
TI  - Biogenesis of zinc storage granules in Drosophila melanogaster.
AB  - Membrane transporters and sequestration mechanisms concentrate metal ions
      differentially into discrete subcellular microenvironments for use in protein
      cofactors, signalling, storage or excretion. Here we identify zinc storage
      granules as the insect's major zinc reservoir in principal Malpighian tubule
      epithelial cells of Drosophila melanogaster The concerted action of Adaptor
      Protein-3, Rab32, HOPS and BLOC complexes as well as of the white-scarlet (ABCG2
      like) and ZnT35C (ZnT2/ZnT3/ZnT8-like) transporters is required for zinc storage
      granule biogenesis. Due to lysosome-related organelle defects caused by mutations
      in the homologous human genes, patients with Hermansky-Pudlak syndrome may lack
      zinc granules in beta pancreatic cells, intestinal paneth cells and presynaptic
      vesicles of hippocampal mossy fibers.

PMID- 29367280
TI  - Do active modes of transport cause lower body mass index? Findings from the
      HABITAT longitudinal study.
AB  - BACKGROUND: Few studies have examined the causal relationship between transport
      mode and body mass index (BMI). METHODS: We examined between-person differences
      and within-person changes in BMI by transport mode over four time points between
      2007 and 2013. Data were from the How Areas in Brisbane Influence HealTh and
      AcTivity project, a population-representative study of persons aged 40-65 in 2007
      (baseline) residing in 200 neighbourhoods in Brisbane, Australia. The analytic
      sample comprised 9931 respondents who reported on their main transport for all
      travel purposes (work-related and non-work-related). Transport mode was measured
      as private motor vehicle (PMV), public transport, walking and cycling. Self
      reported height and weight were used to derive BMI. Sex-specific analyses were
      conducted using multilevel hybrid regression before and after adjustment for time
      varying and time-invariant confounders. RESULTS: Independent of transport mode
      and after adjustment for confounders, average BMI increased significantly and
      linearly across the four time points for both men and women. Men and women who
      walked or cycled had a significantly lower BMI than their counterparts who used a
      PMV. BMI was nearly always lower during the time men and women walked or cycled
      than when they used a PMV; however, few statistically significant differences
      were observed. For women, BMI was significantly higher during the time they used
      public transport than when using a PMV. CONCLUSION: The findings suggest a causal
      association between transport mode and BMI and support calls from health
      authorities to promote walking and cycling for transport as a way of
      incorporating physical activity into everyday life to reduce the risk of chronic
      disease.

PMID- 29367281
TI  - Prison environment and non-communicable chronic disease modifiable risk factors:
      length of incarceration trend analysis in Mexico City.
AB  - BACKGROUND: There is a lack of evidence regarding chronic disease modifiable risk
      factors among prisoner populations in Latin America. The purpose of this study
      was to estimate the prevalence of modifiable risk factors for chronic diseases
      and to assess their relationship with length of incarceration. METHODS: We
      analysed data from a cross sectional study in which 4241 prisoners were randomly
      selected to answer a questionnaire with socio-demographic and health behaviour
      content using an audio computer-assisted self-interview format. Physical activity
      (PA), low-quality diet, current smoking and alcohol or cocaine use during the
      last month in prison were our main outcomes. Quantile regression models and
      logistic regression models were performed. RESULTS: Our final analytical sample
      consisted of 3774 prisoners from four Mexico City prisons. PA was estimated as
      579 median metabolic equivalents-min/week, prevalence of alcohol use was 23.4%,
      cocaine use was 24.2% and current smoking was 53.2%. Our results suggest that, as
      length of incarceration increased, PA as well as alcohol and cocaine use
      increased, whereas the quality of diet decreased. CONCLUSION: This study supports
      the hypothesis that exposure to prison environment (measured by length of
      incarceration) fosters modifiable risk factors for chronic diseases, particularly
      diet quality and cocaine use.

PMID- 29367282
TI  - Panic in a (Zika) hot zone.

PMID- 29367283
TI  - Does adiposity mediate the relationship between socioeconomic position and non
      allergic asthma in childhood?
AB  - BACKGROUND: Despite its high prevalence, early onset and chronic nature, the
      causes of asthma are not clearly established. The present study examined a
      plausible but untested relationship in the development of non-allergic asthma; an
      asthma phenotype closely linked to deprivation and other preventable risk
      factors. Our aim was to determine the mediating role of adiposity in the
      relationship between socioeconomic position in infancy and non-allergic asthma
      emergence in mid-childhood. METHODS: To estimate the causal indirect effect of
      adiposity we applied the parametric g-computational procedure to 6203 singleton
      children from the UK Millennium Cohort Study. Adiposity was measured at age 7 by
      body mass index, waist circumference and waist circumference-to-height ratio.
      Children who developed non-allergic asthma between the age of 7 and 14 were
      compared with children without allergies or allergic asthma at these ages.
      RESULTS: We found no evidence to suggest that adiposity is a mediator in the
      relationship between socioeconomic position and the development of non-allergic
      asthma in mid-childhood. After adjustment for risk factors, the direct effect of
      socioeconomic position remained; children in the lowest tertile of socioeconomic
      position had a 43% (OR 1.43, 95% CI 1.38 to 1.49) greater odds of developing non
      allergic asthma compared with the highest tertile. CONCLUSIONS: Adiposity at age
      7 does not mediate the relationship between socioeconomic position and non
      allergic asthma. The results suggest that improving socioeconomic conditions and
      promoting healthy weight are both important in reducing the development of non
      allergic asthma in early to mid-childhood.

PMID- 29367284
TI  - Biomarker assessment of tobacco smoking exposure and risk of dementia death:
      pooling of individual participant data from 14 cohort studies.
AB  - BACKGROUND: While there is a suggestion that self-reported tobacco smoking may be
      a risk factor for dementia, to date, it has not been possible to explore the
      thresholds at which this exposure elevates risk. Accordingly, our aim was to
      relate cotinine, a biomarker of tobacco smoking, to risk of dementia death.
      METHODS: We pooled 14 prospective cohort studies that held data on cotinine
      (plasma or saliva), covariates and death records. RESULTS: In the 33 032 study
      members (17 107 women) with salivary cotinine data, a mean duration of 8.3 years
      of follow-up gave rise to 135 deaths ascribed to dementia; while in 15 130 study
      members (7995 women) with plasma cotinine data, there were 119 dementia deaths
      during 14.3 years of mortality surveillance. After multiple adjustment, both
      plasma cotinine (per 1 SD higher cotinine; 95% CI 1.29; (1.05 to 1.59)) and
      salivary cotinine (1.10 (0.89 to 1.36)) were positively related to dementia risk,
      with stronger effects apparent for plasma. CONCLUSION: Our finding that plasma
      cotinine was related to an elevated risk of dementia death warrants testing in
      studies with measures of disease onset as opposed to just mortality.

PMID- 29367286
TI  - Attention, attention: your most valuable scientific assets are under attack: How
      digital contraptions and online accounts are contributing to academic attention
      deficit disorder.

PMID- 29367285
TI  - Che-1 is targeted by c-Myc to sustain proliferation in pre-B-cell acute
      lymphoblastic leukemia.
AB  - Despite progress in treating B-cell precursor acute lymphoblastic leukemia (BCP
      ALL), disease recurrence remains the main cause of treatment failure. New
      strategies to improve therapeutic outcomes are needed, particularly in high-risk
      relapsed patients. Che-1/AATF (Che-1) is an RNA polymerase II-binding protein
      involved in proliferation and tumor survival, but its role in hematological
      malignancies has not been clarified. Here, we show that Che-1 is overexpressed in
      pediatric BCP-ALL during disease onset and at relapse, and that its depletion
      inhibits the proliferation of BCP-ALL cells. Furthermore, we report that c-Myc
      regulates Che-1 expression by direct binding to its promoter and describe a
      strict correlation between Che-1 expression and c-Myc expression. RNA-seq
      analyses upon Che-1 or c-Myc depletion reveal a strong overlap of the respective
      controlled pathways. Genomewide ChIP-seq experiments suggest that Che-1 acts as a
      downstream effector of c-Myc. These results identify the pivotal role of Che-1 in
      the control of BCP-ALL proliferation and present the protein as a possible
      therapeutic target in children with relapsed BCP-ALL.

PMID- 29367288
TI  - How Cells Fold the Cerebral Cortex.
AB  - Folding of the cerebral cortex is as highly intriguing as poorly understood. At
      first sight, this may appear as simple tissue crumpling inside an excessively
      small cranium, but the process is clearly much more complex and developmentally
      predetermined. Whereas theoretical modeling supports a critical role for
      biomechanics, experimental evidence demonstrates the fundamental role of specific
      progenitor cell types, cellular processes, and genetic programs on cortical
      folding.Dual Perspectives Companion Paper: How Forces Fold the Cerebral Cortex,
      by Christopher D. Kroenke and Philip V. Bayly.

PMID- 29367287
TI  - How Forces Fold the Cerebral Cortex.
AB  - Improved understanding of the factors that govern folding of the cerebral cortex
      is desirable for many reasons. The existence of consistent patterns in folding
      within and between species suggests a fundamental role in brain function.
      Abnormal folding patterns found in individuals affected by a diverse array of
      neurodevelopmental disorders underline the clinical relevance of understanding
      the folding process. Recent experimental and computational efforts to elucidate
      the biomechanical forces involved in cerebral cortical folding have converged on
      a consistent approach. Brain growth is modeled with two components: an expanding
      outer zone, destined to become the cerebral cortex, is mechanically coupled to an
      inner zone, destined to become white matter, that grows at a slower rate, perhaps
      in response to stress induced by expansion from the outer layer. This framework
      is consistent with experimentally observed internal forces in developing brains,
      and with observations of the folding process in physical models. In addition,
      computational simulations based on this foundation can produce folding patterns
      that recapitulate the characteristics of folding patterns found in gyroencephalic
      brains. This perspective establishes the importance of mechanical forces in our
      current understanding of how brains fold, and identifies realistic ranges for
      specific parameters in biophysical models of developing brain tissue. However,
      further refinement of this approach is needed. An understanding of mechanical
      forces that arise during brain development and their cellular-level origins is
      necessary to interpret the consequences of abnormal brain folding and its role in
      functional deficits as well as neurodevelopmental disease.Dual Perspectives
      Companion Paper: How Cells Fold the Cerebral Cortex, by Victor Borrell.

PMID- 29367290
TI  - Sixty seconds on . . . loneliness.

PMID- 29367289
TI  - Readiness Potential and Neuronal Determinism: New Insights on Libet Experiment.

PMID- 29367291
TI  - False-Negative Serum Cryptococcal Lateral Flow Assay Result Due to the Prozone
      Phenomenon.

PMID- 29367292
TI  - CLSI Methods Development and Standardization Working Group Best Practices for
      Evaluation of Antimicrobial Susceptibility Tests.
AB  - Effective evaluations of antimicrobial susceptibility tests (ASTs) require robust
      study design. The Clinical and Laboratory Standards Institute (CLSI) Subcommittee
      on Antimicrobial Susceptibility Testing has recognized that many published
      studies reporting the performance of commercial ASTs (cASTs) suffer from major
      design and/or analysis flaws, rendering the results difficult or impossible to
      interpret. This minireview outlines the current consensus of the Methods
      Development and Standardization Working Group of the CLSI Subcommittee on
      Antimicrobial Susceptibility Testing regarding best practices for systematic
      evaluation of the performance of an AST, including the analysis and presentation
      of essential data intended for publication.

PMID- 29367293
TI  - Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation
      of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol
      (STAMP) Trial.
AB  - The performance of blood culture for monitoring candidemia clearance is hampered
      by its low sensitivity, especially during antifungal therapy. The T2 magnetic
      resonance (T2MR) assay combines magnetic resonance with nanotechnology to
      identify whole Candida species cells. A multicenter clinical trial studied the
      performance of T2MR in monitoring candidemia clearance compared to blood culture.
      Adults with a blood culture positive for yeast were enrolled and had blood
      cultures and T2MR testing performed on prespecified days. Thirty-one patients
      completed the trial. Thirteen of the 31 patients (41.9%) had at least one
      positive surveillance T2MR and/or blood culture result. All positive blood
      cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance
      in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an
      accompanying positive blood culture. There was one case of discordance in species
      identification between T2MR and the preenrollment blood culture with evidence to
      support deep-seated infection by the Candida spp. detected by the T2MR assay.
      Based on the log rank test, there was a statistically significant improvement in
      posttreatment surveillance using the T2MR assay compared to blood culture (P =
      0.004). Limitations of the study include the small sample size and lack of
      outcome data. In conclusion, the T2MR assay significantly outperformed blood
      cultures for monitoring the clearance of candidemia in patients receiving
      antifungal therapy and may be useful in determining adequate source control,
      timing for deescalation, and optimal duration of treatment. However, further
      studies are needed to determine the viability of Candida species cells detected
      by the T2MR assay and correlate the results with patient outcomes. (This study is
      registered at ClinicalTrials.gov under registration number NCT02163889.).

PMID- 29367294
TI  - Evaluation of Two DNA Extraction Methods for Detection of Strongyloides
      stercoralis Infection.
AB  - Strongyloides stercoralis is present worldwide, but its prevalence is still
      uncertain, mainly due to the lack of sensitivity of diagnostic methods. Molecular
      techniques are under development, but a standardized protocol is still
      unavailable. We compared the sensitivity of real-time PCR, using two extraction
      protocols, with that of the Baermann technique. Samples were collected in the
      framework of the baseline screening of a randomized clinical trial evaluating
      moxidectin against S. stercoralis in Lao People's Democratic Republic. Two stool
      samples from each participant were processed by the Baermann method, and one
      subsample was processed by PCR. DNA was extracted using the QIAamp DNA stool
      minikit based on the standard protocol for the QIAamp DNA minikit (QIA) and using
      a modification of the QIA procedure (POL). Subsequently, all extracted samples
      were analyzed by real-time PCR. Overall, 95 samples were analyzed by the three
      diagnostic methods. Sixty-nine (72.6%) samples were positive according to the
      Baermann method, 25 (26.3%) by the QIA method, and 62 (65.3%) by the POL method.
      The sensitivities were 86% (95% confidence interval [CI], 76.7 to 92.9), 31.0%
      (95% CI, 21.3 to 42.6), and 78.0% (95% CI, 66.8 to 86.1) for the Baermann, QIA,
      and POL methods, respectively. The sensitivities calculated for each day of the
      Baermann method separately were 60% (48.4 to 70.8%) and 64% (52.2 to 74.2%) for
      days 1 and 2, respectively. In conclusion, the POL method revealed a good
      performance and was comparable to the Baermann test performed on two stool
      samples and superior to the Baermann method performed on one stool sample.
      Additional studies are needed to standardize a PCR protocol for S. stercoralis
      diagnosis.

PMID- 29367295
TI  - Validation of Active Surveillance Testing for Clostridium difficile Colonization
      Using the cobas Cdiff Test.
AB  - Clostridium difficile infection (CDI) is not declining in the United States.
      Nucleic acid amplification tests (NAAT) are used as part of active surveillance
      testing programs to prevent health care-associated infection. The objective of
      this study was to validate the cobas Cdiff Test on the cobas 4800 System (cobas)
      within a four-hospital system using prospectively collected perirectal swabs from
      asymptomatic patients at admission and during monthly intensive care unit (ICU)
      screening in an infection control CDI reduction program. Performance of the cobas
      was compared to that of toxigenic culture. Each positive cobas sample and the
      next following negative patient swab were cultured. The study design gave 273
      samples processed by both cobas (137 positive and 136 negative) and culture (one
      negative swab was not cultured). Discrepant analysis was performed using a second
      NAAT, the Xpert C. difficile Epi test (Xpert). This strategy was compared to a
      medical record review for antibiotic receipt that would inhibit growth of C.
      difficile in colonic stool. None of the cobas-negative samples were culture
      positive. The cobas positive predictive value was 75.2% (95% confidence interval
      [CI], 66.9% to 82%) and positive percent agreement was 100% (95% CI, 96.0% to
      100%). Overall agreement between cobas and direct toxigenic culture was 87.6%
      (95% CI, 83.1% to 91%). For the cobas-positive/culture-negative (discrepant)
      samples, 7 Xpert-positive samples were from patients receiving inhibitory
      antimicrobials; only 4 of 23 Xpert-negative samples received these agents (P =
      0.00006). Our results support use of the cobas as a reliable assay for an active
      surveillance testing program to detect asymptomatic carriers of toxigenic C.
      difficile.

PMID- 29367296
TI  - Rapid, Accurate Identification of Candida auris by Using a Novel Matrix-Assisted
      Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)
      Database (Library).

PMID- 29367298
TI  - Evaluation of Non-Tissue Culture- versus Tissue Culture-Treated Microplates for
      Oritavancin Susceptibility Testing.

PMID- 29367297
TI  - An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31
      Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme
      Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the
      Netherlands.
AB  - Two-tier serology testing is most frequently used for the diagnosis of Lyme
      borreliosis (LB); however, a positive result is no proof of active disease. To
      establish a diagnosis of active LB, better diagnostics are needed. Tests
      investigating the cellular immune system are available, but studies evaluating
      the utility of these tests on well-defined patient populations are lacking.
      Therefore, we investigated the utility of an enzyme-linked immunosorbent spot
      (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood
      mononuclear cells (PBMCs) of various study groups were stimulated by using
      Borrelia burgdorferi strain B31 and various recombinant antigens, and
      subsequently, the number of Borrelia-specific interferon gamma (IFN-gamma)
      secreting T cells was measured. We included 33 active and 37 treated Lyme
      neuroborreliosis patients, 28 healthy individuals treated for an early
      manifestation of LB in the past, and 145 untreated healthy individuals. The
      median numbers of B. burgdorferi B31-specific IFN-gamma-secreting T cells/2.5 *
      105 PBMCs did not differ between active Lyme neuroborreliosis patients (6.0;
      interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients
      (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9)
      (P = 1.000); however, the median number of B. burgdorferi B31-specific IFN-gamma
      secreting T cells/2.5 * 105 PBMCs among untreated healthy individuals was lower
      (2.0; IQR, 0.5 to 3.9) (P <= 0.016). We conclude that the Borrelia ELISpot assay,
      measuring the number of B. burgdorferi B31-specific IFN-gamma-secreting T
      cells/2.5 * 105 PBMCs, correlates with exposure to the Borrelia bacterium but
      cannot be used for the diagnosis of active Lyme neuroborreliosis.

PMID- 29367299
TI  - Molecular Prediction of the O157:H-Negative Phenotype Prevalent in Australian
      Shiga Toxin-Producing Escherichia coli Cases Improves Concordance of In Silico
      Serotyping with Phenotypic Motility.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen, and
      serotype O157:H7 is typically associated with severe disease. Australia is unique
      in its STEC epidemiology, as severe cases are typically associated with non-O157
      serogroups, and locally acquired O157 isolates are H-negative/nonmotile. The H
      negative phenotype and reduced severity of disease compared to that associated
      with H7/motile strains are distinct features of Australian O157 strains, but the
      molecular mechanism behind this phenotype has not been reported. Accurate
      characterization of the H-negative phenotype is important in epidemiological
      surveillance of STEC. Serotyping is moving away from phenotype-based methods, as
      next generation sequencing allows rapid extrapolation of serotype through in
      silico detection of the O-antigen processing genes, wzx, wzy, wzm, and wzt, and
      the H-antigen gene, fliC The detection and genotyping of fliC alone is unable to
      determine the motility of the strain. Typically, most Australian O157:H-negative
      strains carry an H7 genotype yet phenotypically are nonmotile; thus, many are
      mischaracterized as H7 strains by in silico serotyping tools. Comparative genomic
      analysis of flagellar genes between Australian and international isolates was
      performed and an insertion at nucleotide (nt) 125 in the flgF gene was identified
      in H-negative isolates. Chi-square results showed that this insertion was
      significantly associated with the H-negative phenotype (P < 0.0001). Phylogenetic
      analysis was also completed and showed that the Australian H-negative isolates
      with the insertion in flgF represent a clade within the O157 serogroup, distinct
      from O157:H7 serotypes. This study provides a genetic target for inferring the
      nonmotile phenotype of Australian O157 STEC, which increases the predictive value
      of in silico serotyping.

PMID- 29367300
TI  - Evaluation of Two Protein Extraction Protocols Based on Freezing and Mechanical
      Disruption for Identifying Nontuberculous Mycobacteria by Matrix-Assisted Laser
      Desorption Ionization-Time of Flight Mass Spectrometry from Liquid and Solid
      Cultures.
AB  - Matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) has proved to be a useful diagnostic method for identifying
      conventional bacteria. In the case of mycobacteria, a good protein extraction
      protocol is essential in order to obtain reliable identification results. To
      date, no such protocol has been definitively established. The aim of this study
      was to compare the manufacturer's recommended protein extraction protocol
      (protocol A) with two novel protocols (protocols B and C), which apply different
      freezing temperatures and mechanical disruption times using an automatic tissue
      homogenizer. A total of 302 clinical isolates, comprising 41 nontuberculous
      mycobacteria (NTM) species, were grown in parallel on solid and liquid media and
      analyzed: 174 isolates were slow-growing mycobacteria (SGM) and 128 isolates were
      rapid-growing mycobacteria (RGM). Overall, MALDI-TOF MS identified a higher
      number of NTM isolates from solid than from liquid media, especially with
      protocol C (83.4 and 68.2%, respectively; P < 0.05). From solid media, this
      protein extraction method identified 57.9 and 3.9% more isolates than protocols A
      (P < 0.001) and B (P < 0.05), respectively. In the case of liquid media, protocol
      C identified 49.7 and 6.3% more isolates than protocols A and B, respectively (P
      < 0.001). With regard to the growth rate, MALDI-TOF MS identified more RGM
      isolates than SGM isolates in all of the protocols studied. In conclusion, the
      application of freezing and automatic tissue homogenizer improved protein
      extraction of NTM and boosted identification rates. Consequently, MALDI-TOF MS,
      which is a cheap and simple method, could be a helpful tool for identifying NTM
      species in clinical laboratories.

PMID- 29367302
TI  - CORRECTION.

PMID- 29367301
TI  - Mycobacterial spindle cell pseudotumour: epidemiology and clinical outcomes.
AB  - INTRODUCTION: Mycobacterial spindle cell pseudotumour (MSP) is a rare disease
      characterised by tumour-like local proliferation of spindle-shaped histiocytes
      containing acid-fast positive mycobacteria. The aim of this literature review is
      to describe the clinical parameters and treatment outcomes of patients with MSP.
      METHODS: A literature search was conducted using the search terms related to
      mycobacteria and spindle cell tumours. A previously unreported stem cell
      transplant recipient from our institution diagnosed with MSP was also included.
      Demographics, comorbidities, site of infection, treatment and clinical outcomes
      were analysed. RESULTS: Fifty-one patients were analysed. Twenty-six (51%) had
      HIV infection. Mycobacterium avium complex was the most frequent organism
      isolated in 24 (47.1%) followed by Mycobacterium tuberculosis complex in eight
      (16%) cases. Lymph nodes were the most common site of infection (45.1%). Twenty
      (39.2%) patients received antimycobacterial agents, 12 (23.5%) underwent surgical
      resection and six (11.8%) received antimycobacterial agents plus surgery.
      Treatment was successful in 24 (47.1%) patients and failed in 15 (29.4%); 13 of
      these 15 patients died. Antimycobacterial therapy was significantly associated
      with successful outcome compared with surgical resection or no treatment
      (P<0.001). CONCLUSION: MSP is a rare condition associated primarily with
      immunodeficiencies. Antimycobacterial therapy is significantly associated with
      successful outcome.

PMID- 29367303
TI  - Design Stars: How GRF-INTERACTING FACTORs Help Determine the Layout of the Root
      Tip.

PMID- 29367304
TI  - Interregulation of CDKA/CDK1 and the Plant-Specific Cyclin-Dependent Kinase CDKB
      in Control of the Chlamydomonas Cell Cycle.
AB  - The cyclin-dependent kinase CDK1 is essential for mitosis in fungi and animals.
      Plant genomes contain the CDK1 ortholog CDKA and a plant kingdom-specific
      relative, CDKB. The green alga Chlamydomonas reinhardtii has a long G1 growth
      period followed by rapid cycles of DNA replication and cell division. We show
      that null alleles of CDKA extend the growth period prior to the first division
      cycle and modestly extend the subsequent division cycles, but do not prevent cell
      division, indicating at most a minor role for the CDK1 ortholog in mitosis in
      Chlamydomonas. A null allele of cyclin A has a similar though less extreme
      phenotype. In contrast, both CDKB and cyclin B are essential for mitosis. CDK
      kinase activity measurements imply that the predominant in vivo complexes are
      probably cyclin A-CDKA and cyclin B-CDKB. We propose a negative feedback loop:
      CDKA activates cyclin B-CDKB. Cyclin B-CDKB in turn promotes mitotic entry and
      inactivates cyclin A-CDKA. Cyclin A-CDKA and cyclin B-CDKB may redundantly
      promote DNA replication. We show that the anaphase-promoting complex is required
      for inactivation of both CDKA and CDKB and is essential for anaphase. These
      results are consistent with findings in Arabidopsis thaliana and may delineate
      the core of plant kingdom cell cycle control that, compared with the well-studied
      yeast and animal systems, exhibits deep conservation in some respects and
      striking divergence in others.

PMID- 29367306
TI  - A Conserved Mechanism to Terminate Floral Meristems.

PMID- 29367305
TI  - Role of the Nod Factor Hydrolase MtNFH1 in Regulating Nod Factor Levels during
      Rhizobial Infection and in Mature Nodules of Medicago truncatula.
AB  - Establishment of symbiosis between legumes and nitrogen-fixing rhizobia depends
      on bacterial Nod factors (NFs) that trigger symbiosis-related NF signaling in
      host plants. NFs are modified oligosaccharides of chitin with a fatty acid
      moiety. NFs can be cleaved and inactivated by host enzymes, such as MtNFH1
      (MEDICAGO TRUNCATULA NOD FACTOR HYDROLASE1). In contrast to related chitinases,
      MtNFH1 hydrolyzes neither chitin nor chitin fragments, indicating a high cleavage
      preference for NFs. Here, we provide evidence for a role of MtNFH1 in the
      symbiosis with Sinorhizobium meliloti Upon rhizobial inoculation, MtNFH1
      accumulated at the curled tip of root hairs, in the so-called infection chamber.
      Mutant analysis revealed that lack of MtNFH1 delayed rhizobial root hair
      infection, suggesting that excess amounts of NFs negatively affect the initiation
      of infection threads. MtNFH1 deficiency resulted in nodule hypertrophy and
      abnormal nodule branching of young nodules. Nodule branching was also stimulated
      in plants expressing MtNFH1 driven by a tandem CaMV 35S promoter and plants
      inoculated by a NF-overproducing S. meliloti strain. We suggest that fine-tuning
      of NF levels by MtNFH1 is necessary for optimal root hair infection as well as
      for NF-regulated growth of mature nodules.

PMID- 29367307
TI  - Just one cigarette a day seriously elevates cardiovascular risk.

PMID- 29367308
TI  - The Brief Case: Staphylococcus intermedius Group-Look What the Dog Dragged In.

PMID- 29367309
TI  - Closing the Brief Case: Staphylococcus intermedius Group-Look What the Dog
      Dragged In.

PMID- 29367310
TI  - The Utility of Multiplex Molecular Tests for Enteric Pathogens: a Micro-Comic
      Strip.

PMID- 29367311
TI  - Photo Quiz: Pneumonia and Pyogenic Skin Abscesses in a 79-Year-Old Man.

PMID- 29367312
TI  - Answer to February 2018 Photo Quiz.

PMID- 29367314
TI  - Overdiagnosis: what it is and what it isn't.

PMID- 29367315
TI  - Beliefs, critical thinking and evidence-based medicine.

PMID- 29367313
TI  - Targeted deletion of a 170-kb cluster of LINE-1 repeats and implications for
      regional control.
AB  - Approximately half the mammalian genome is composed of repetitive sequences, and
      accumulating evidence suggests that some may have an impact on genome function.
      Here, we characterized a large array class of repeats of long-interspersed
      elements (LINE-1). Although widely distributed in mammals, locations of such
      arrays are species specific. Using targeted deletion, we asked whether a 170-kb
      LINE-1 array located at a mouse imprinted domain might function as a modulator of
      local transcriptional control. The LINE-1 array is lamina associated in
      differentiated ES cells consistent with its AT-richness, and although imprinting
      occurs both proximally and distally to the array, active LINE-1 transcripts
      within the tract are biallelically expressed. Upon deletion of the array, no
      perturbation of imprinting was observed, and abnormal phenotypes were not
      detected in maternal or paternal heterozygous or homozygous mutant mice. The
      array does not shield nonimprinted genes in the vicinity from local imprinting
      control. Reduced neural expression of protein-coding genes observed upon paternal
      transmission of the deletion is likely due to the removal of a brain-specific
      enhancer embedded within the LINE array. Our findings suggest that presence of a
      170-kb LINE-1 array reflects the tolerance of the site for repeat insertion
      rather than an important genomic function in normal development.

PMID- 29367316
TI  - Rare adverse events in clinical trials: understanding the rule of three.

PMID- 29367317
TI  - Analysis of conference abstract-to-publication rate in UK orthopaedic research.
AB  - Presentation of research at orthopaedic conferences is an important component for
      surgical evidence-based practice. However, there remains uncertainty as to how
      many conference abstracts proceed to achieve full-text publication (FTP) for
      wider dissemination. This study aimed to determine the abstract-to-publication
      rate (APR) of research presented in the largest hip and knee orthopaedic meetings
      in the UK, and to identify predictive factors which influence the APR. All
      published abstracts (n=744) from the 2006, 2008, 2009 and 2010 British Hip
      Society (BHS) and the 2007, 2009, 2010 and 2011 British Association for Surgery
      of the Knee (BASK) annual conference meetings were examined by four researchers
      independently. To determine whether abstracts had been published in full-text
      form, Google Scholar, Medline and EMBASE evidence databases were used to verify
      FTP status. Variables including sample size, statistical significance, grade of
      the first author, research affiliated institution and research design were
      extracted and analysed to identify whether these were associated with FTP. 176
      out of 744 abstracts achieved FTP status (APR: 23.7%). Factors associated with
      FTP status included statistically significant results (P<0.01) and research
      design (P=0.02). Factors not associated included sample size, grade of the first
      author and research affiliated institution (P>0.05). APRs of the assessed BHS and
      BASK annual conference presentations are low in comparison to other scientific
      meetings. Encouragement should be provided to clinicians and academics to submit
      their work for publication to address this short fall, thereby enhancing the
      potential for full-text research publications to inform evidence-based
      orthopaedics.

PMID- 29367319
TI  - External validity, generalisability, applicability and directness: a brief
      primer.
AB  - External validity is a construct that attempts to answer the question of whether
      we can use the results of a study in patients other than those enrolled in the
      study. External validity consists of two unique underlying concepts,
      generalisability and applicability. When the concern is about extending the
      results from a sample to the population from which the sample was drawn, the
      problem is one of generalisability. When the concern is about using inferences
      drawn from study participants in the care of specific patients belonging to any
      population, the problem is one of applicability. Clinicians, guideline developers
      and policymakers do not struggle with generalisability, but often struggle with
      applicability. When applicability is deemed to be low for a certain population,
      certainty in the supporting evidence becomes low due to indirectness.

PMID- 29367318
TI  - Interactive visualisation for interpreting diagnostic test accuracy study
      results.
AB  - Information about the performance of diagnostic tests is typically presented in
      the form of measures of test accuracy such as sensitivity and specificity. These
      measures may be difficult to translate directly into decisions about patient
      treatment, for which information presented in the form of probabilities of
      disease after a positive or a negative test result may be more useful. These
      probabilities depend on the prevalence of the disease, which is likely to vary
      between populations. This article aims to clarify the relationship between pre
      test (prevalence) and post-test probabilities of disease, and presents two free,
      online interactive tools to illustrate this relationship. These tools allow
      probabilities of disease to be compared with decision thresholds above and below
      which different treatment decisions may be indicated. They are intended to help
      those involved in communicating information about diagnostic test performance and
      are likely to be of benefit when teaching these concepts. A substantive example
      is presented using C reactive protein as a diagnostic marker for bacterial
      infection in the older adult population. The tools may also be useful for
      manufacturers of clinical tests in planning product development, for authors of
      test evaluation studies to improve reporting and for users of test evaluations to
      facilitate interpretation and application of the results.

PMID- 29367320
TI  - Catalogue of bias: allocation bias.
AB  - This article is part of a series of articles featuring the Catalogue of Bias
      introduced in this volume of BMJ Evidence-Based Medicine that describes
      allocation bias and outlines its potential impact on research studies and the
      preventive steps to minimise its risk. Allocation bias is a type of selection
      bias and is relevant to clinical trials of interventions. Knowledge of
      interventions prior to group allocation can result in systematic differences in
      important characteristics that could influence study findings. Allocation bias
      can overestimate effect size by up to 30%-40%. Sequentially numbered, opaque,
      sealed envelopes; containers; pharmacy-controlled randomisation and central
      computer randomisation are methods to minimise allocation bias.

PMID- 29367321
TI  - Catalogue of bias: attrition bias.
AB  - This article is part of a series of articles featuring the Catalogue of Bias
      introduced in this volume of BMJ Evidence-Based Medicine that describes attrition
      bias and outlines its potential impact on research studies and the preventive
      steps to minimise its risk. Attrition bias is a type of selection bias due to
      systematic differences between study groups in the number and the way
      participants are lost from a study. Differences between people who leave a study
      and those who continue, particularly between study groups, can be the reason for
      any observed effect and not the intervention itself. Associations for mortality
      in trials of tranexamic acid and upper gastrointestinal bleeding were no longer
      apparent after studies with high or unclear risk of attrition bias were removed.
      Over-recruitment can help prevent important attrition bias. Sampling weights and
      tailored replenishment samples can help to compensate for the effects of
      attrition bias when present.

PMID- 29367323
TI  - Correction: Ten essential papers for the practice of evidence-based medicine.

PMID- 29367322
TI  - Catalogue of bias: observer bias.
AB  - This article is part of a series featured from the Catalogue of Bias introduced
      in this volume of BMJ Evidence-Based Medicine that describes biases and outlines
      their potential impact in research studies. Observer bias is systematic
      discrepancy from the truth during the process of observing and recording
      information for a study. Many healthcare observations are at risk of this bias.
      Evidence shows that treatment effect estimates can be exaggerated by a third to
      two-thirds in the presence of observer bias in outcome assessment. Preventing
      observer bias involves proper masking in intervention studies including the use
      of matched placebo interventions where appropriate and training of observers to
      make assessment consistent and reduce biases resulting from conscious or
      unconscious prejudices. Where observers are involved in a research study, it is
      probably not possible for the study to be entirely free of observer biases.

PMID- 29367324
TI  - Key Concepts for Informed Health Choices: a framework for helping people learn
      how to assess treatment claims and make informed choices.
AB  - Many claims about the effects of treatments, though well intentioned, are wrong.
      Indeed, they are sometimes deliberately misleading to serve interests other than
      the well-being of patients and the public. People need to know how to spot
      unreliable treatment claims so that they can protect themselves and others from
      harm. The ability to assess the trustworthiness of treatment claims is often
      lacking. Acquiring this ability depends on being familiar with, and correctly
      applying, some key concepts, for example, that' association is not the same as
      causation.' The Informed Health Choices (IHC) Project has identified 36 such
      concepts and shown that people can be taught to use them in decision making. A
      randomised trial in Uganda, for example, showed that primary school children with
      poor reading skills could be taught to apply 12 of the IHC Key Concepts. The list
      of IHC Key Concepts has proven to be effective in providing a framework for
      developing and evaluating IHC resources to help children to think critically
      about treatment claims. The list also provides a framework for retrieving, coding
      and organising other teaching and learning materials for learners of any age. It
      should help teachers, researchers, clinicians, and patients to structure critical
      thinking about the trustworthiness of claims about treatment effects.

PMID- 29367325
TI  - When is a guideline not a guideline? The devil is in the details.

PMID- 29367326
TI  - High incidence of cervical cancer in women over 60 is likely due to less
      intensive cervical screening in this generation of women.

PMID- 29367327
TI  - Trial supports targeted radiotherapy for early breast cancer but protocol still
      requires 3 weeks of daily therapy.

PMID- 29367328
TI  - Low-dose levothyroxine did not improve symptoms in asymptomatic older people with
      subclinical hypothyroidism.

PMID- 29367329
TI  - NSAIDs are superior to paracetamol for osteoarthritic pain and function in a
      network meta-analysis.

PMID- 29367330
TI  - Angiotensin II increases blood pressure in patients with refractory vasodilatory
      shock.

PMID- 29367331
TI  - Effect size in CANTOS trial.

PMID- 29367332
TI  - Effect of Dysphagia Screening Strategies on Clinical Outcomes After Stroke: A
      Systematic Review for the 2018 Guidelines for the Early Management of Patients
      With Acute Ischemic Stroke.
AB  - INTRODUCTION: Dysphagia screening protocols have been recommended to identify
      patients at risk for aspiration. The American Heart Association convened an
      evidence review committee to systematically review evidence for the effectiveness
      of dysphagia screening protocols to reduce the risk of pneumonia, death, or
      dependency after stroke. METHODS: The Medline, Embase, and Cochrane databases
      were searched on November 1, 2016, to identify randomized controlled trials
      (RCTs) comparing dysphagia screening protocols or quality interventions with
      increased dysphagia screening rates and reporting outcomes of pneumonia, death,
      or dependency. RESULTS: Three RCTs were identified. One RCT found that a combined
      nursing quality improvement intervention targeting fever and glucose management
      and dysphagia screening reduced death and dependency but without reducing the
      pneumonia rate. Another RCT failed to find evidence that pneumonia rates were
      reduced by adding the cough reflex to routine dysphagia screening. A smaller RCT
      randomly assigned 2 hospital wards to a stroke care pathway including dysphagia
      screening or regular care and found that patients on the stroke care pathway were
      less likely to require intubation and mechanical ventilation; however, the study
      was small and at risk for bias. CONCLUSIONS: There were insufficient RCT data to
      determine the effect of dysphagia screening protocols on reducing the rates of
      pneumonia, death, or dependency after stroke. Additional trials are needed to
      compare the validity, feasibility, and clinical effectiveness of different
      screening methods for dysphagia.

PMID- 29367333
TI  - Accuracy of Prediction Instruments for Diagnosing Large Vessel Occlusion in
      Individuals With Suspected Stroke: A Systematic Review for the 2018 Guidelines
      for the Early Management of Patients With Acute Ischemic Stroke.
AB  - INTRODUCTION: Endovascular thrombectomy is a highly efficacious treatment for
      large vessel occlusion (LVO). LVO prediction instruments, based on stroke signs
      and symptoms, have been proposed to identify stroke patients with LVO for rapid
      transport to endovascular thrombectomy-capable hospitals. This evidence review
      committee was commissioned by the American Heart Association/American Stroke
      Association to systematically review evidence for the accuracy of LVO prediction
      instruments. METHODS: Medline, Embase, and Cochrane databases were searched on
      October 27, 2016. Study quality was assessed with the Quality Assessment of
      Diagnostic Accuracy-2 tool. RESULTS: Thirty-six relevant studies were identified.
      Most studies (21 of 36) recruited patients with ischemic stroke, with few studies
      in the prehospital setting (4 of 36) and in populations that included hemorrhagic
      stroke or stroke mimics (12 of 36). The most frequently studied prediction
      instrument was the National Institutes of Health Stroke Scale. Most studies had
      either some risk of bias or unclear risk of bias. Reported discrimination of LVO
      mostly ranged from 0.70 to 0.85, as measured by the C statistic. In meta
      analysis, sensitivity was as high as 87% and specificity was as high as 90%, but
      no threshold on any instruments predicted LVO with both high sensitivity and
      specificity. With a positive LVO prediction test, the probability of LVO could be
      50% to 60% (depending on the LVO prevalence in the population), but the
      probability of LVO with a negative test could still be >=10%. CONCLUSIONS: No
      scale predicted LVO with both high sensitivity and high specificity. Systems that
      use LVO prediction instruments for triage will miss some patients with LVO and
      milder stroke. More prospective studies are needed to assess the accuracy of LVO
      prediction instruments in the prehospital setting in all patients with suspected
      stroke, including patients with hemorrhagic stroke and stroke mimics.

PMID- 29367334
TI  - 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke:
      A Guideline for Healthcare Professionals From the American Heart
      Association/American Stroke Association.
AB  - BACKGROUND AND PURPOSE: The purpose of these guidelines is to provide an up-to
      date comprehensive set of recommendations for clinicians caring for adult
      patients with acute arterial ischemic stroke in a single document. The intended
      audiences are prehospital care providers, physicians, allied health
      professionals, and hospital administrators. These guidelines supersede the 2013
      guidelines and subsequent updates. METHODS: Members of the writing group were
      appointed by the American Heart Association Stroke Council's Scientific
      Statements Oversight Committee, representing various areas of medical expertise.
      Strict adherence to the American Heart Association conflict of interest policy
      was maintained. Members were not allowed to participate in discussions or to vote
      on topics relevant to their relations with industry. The members of the writing
      group unanimously approved all recommendations except when relations with
      industry precluded members voting. Prerelease review of the draft guideline was
      performed by 4 expert peer reviewers and by the members of the Stroke Council's
      Scientific Statements Oversight Committee and Stroke Council Leadership
      Committee. These guidelines use the American College of Cardiology/American Heart
      Association 2015 Class of Recommendations and Levels of Evidence and the new
      American Heart Association guidelines format. RESULTS: These guidelines detail
      prehospital care, urgent and emergency evaluation and treatment with intravenous
      and intra-arterial therapies, and in-hospital management, including secondary
      prevention measures that are appropriately instituted within the first 2 weeks.
      The guidelines support the overarching concept of stroke systems of care in both
      the prehospital and hospital settings. CONCLUSIONS: These guidelines are based on
      the best evidence currently available. In many instances, however, only limited
      data exist demonstrating the urgent need for continued research on treatment of
      acute ischemic stroke.

PMID- 29367335
TI  - 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke.

PMID- 29367336
TI  - Late Window Paradox.

PMID- 29367337
TI  - An essential thioredoxin is involved in the control of the cell cycle in the
      bacterium Caulobacter crescentus.
AB  - Thioredoxins (Trxs) are antioxidant proteins that are conserved among all
      species. These proteins have been extensively studied and perform reducing
      reactions on a broad range of substrates. Here, we identified Caulobacter
      crescentus Trx1 (CCNA_03653; CcTrx1) as an oxidoreductase that is involved in the
      cell cycle progression of this model bacterium and is required to sustain life.
      Intriguingly, the abundance of CcTrx1 varies throughout the C. crescentus cell
      cycle: although the expression of CcTrx1 is induced in stalked cells, right
      before DNA replication initiation, CcTrx1 is actively degraded by the ClpXP
      protease in predivisional cells. Importantly, we demonstrated that regulation of
      the abundance of CcTrx1 is crucial for cell growth and survival as modulating
      CcTrx1 levels leads to cell death. Finally, we also report a comprehensive
      biochemical and structural characterization of this unique and essential Trx. The
      requirement to precisely control the abundance of CcTrx1 for cell survival
      underlines the importance of redox control for optimal cell cycle progression in
      C. crescentus.

PMID- 29367338
TI  - Structure-function analyses generate novel specificities to assemble the
      components of multienzyme bacterial cellulosome complexes.
AB  - The cellulosome is a remarkably intricate multienzyme nanomachine produced by
      anaerobic bacteria to degrade plant cell wall polysaccharides. Cellulosome
      assembly is mediated through binding of enzyme-borne dockerin modules to cohesin
      modules of the primary scaffoldin subunit. The anaerobic bacterium Acetivibrio
      cellulolyticus produces a highly intricate cellulosome comprising an adaptor
      scaffoldin, ScaB, whose cohesins interact with the dockerin of the primary
      scaffoldin (ScaA) that integrates the cellulosomal enzymes. The ScaB dockerin
      selectively binds to cohesin modules in ScaC that anchors the cellulosome onto
      the cell surface. Correct cellulosome assembly requires distinct specificities
      displayed by structurally related type-I cohesin-dockerin pairs that mediate ScaC
      ScaB and ScaA-enzyme assemblies. To explore the mechanism by which these two
      critical protein interactions display their required specificities, we determined
      the crystal structure of the dockerin of a cellulosomal enzyme in complex with a
      ScaA cohesin. The data revealed that the enzyme-borne dockerin binds to the ScaA
      cohesin in two orientations, indicating two identical cohesin-binding sites.
      Combined mutagenesis experiments served to identify amino acid residues that
      modulate type-I cohesin-dockerin specificity in A. cellulolyticus Rational design
      was used to test the hypothesis that the ligand-binding surfaces of ScaA- and
      ScaB-associated dockerins mediate cohesin recognition, independent of the
      structural scaffold. Novel specificities could thus be engineered into one, but
      not both, of the ligand-binding sites of ScaB, whereas attempts at manipulating
      the specificity of the enzyme-associated dockerin were unsuccessful. These data
      indicate that dockerin specificity requires critical interplay between the ligand
      binding surface and the structural scaffold of these modules.

PMID- 29367339
TI  - Systems analysis of the glycoside hydrolase family 18 enzymes from Cellvibrio
      japonicus characterizes essential chitin degradation functions.
AB  - Understanding the strategies used by bacteria to degrade polysaccharides
      constitutes an invaluable tool for biotechnological applications. Bacteria are
      major mediators of polysaccharide degradation in nature; however, the complex
      mechanisms used to detect, degrade, and consume these substrates are not well
      understood, especially for recalcitrant polysaccharides such as chitin. It has
      been previously shown that the model bacterial saprophyte Cellvibrio japonicus is
      able to catabolize chitin, but little is known about the enzymatic machinery
      underlying this capability. Previous analyses of the C. japonicus genome and
      proteome indicated the presence of four glycoside hydrolase family 18 (GH18)
      enzymes, and studies of the proteome indicated that all are involved in chitin
      utilization. Using a combination of in vitro and in vivo approaches, we have
      studied the roles of these four chitinases in chitin bioconversion. Genetic
      analyses showed that only the chi18D gene product is essential for the
      degradation of chitin substrates. Biochemical characterization of the four
      enzymes showed functional differences and synergistic effects during chitin
      degradation, indicating non-redundant roles in the cell. Transcriptomic studies
      revealed complex regulation of the chitin degradation machinery of C. japonicus
      and confirmed the importance of CjChi18D and CjLPMO10A, a previously
      characterized chitin-active enzyme. With this systems biology approach, we
      deciphered the physiological relevance of the glycoside hydrolase family 18
      enzymes for chitin degradation in C. japonicus, and the combination of in vitro
      and in vivo approaches provided a comprehensive understanding of the initial
      stages of chitin degradation by this bacterium.

PMID- 29367341
TI  - Defining the binding determinants of Shewanella oneidensis OxyR: Implications for
      the link between the contracted OxyR regulon and adaptation.
AB  - It is well-established that OxyR functions as a transcriptional activator of the
      peroxide stress response in bacteria, primarily based on studies on Escherichia
      coli Recent investigations have revealed that OxyRs of some other bacteria can
      regulate gene expression through both repression and activation or repression
      only; however, the underlying mechanisms remain largely unknown. Here, we
      demonstrated in gamma-proteobacteriumShewanella oneidensis regulation of OxyR on
      expression of major catalase gene katB in a dual-control manner through
      interaction with a single site in the promoter region. Under non-stress
      conditions, katB expression was repressed by reduced OxyR (OxyRred), whereas when
      oxidized, OxyR (OxyRoxi) outcompeted OxyRred for the site because of
      substantially enhanced affinity, resulting in a graded response to oxidative
      stress, from repression to derepression to activation. The OxyR-binding motif is
      characterized as a combination of the E. coli motif (tetranucleotides spaced by
      heptanucleotide) and palindromic structure. We provided evidence to suggest that
      the S. oneidensis OxyR regulon is significantly contracted compared with those
      reported, probably containing only five members that are exclusively involved in
      oxygen reactive species scavenging and iron sequestering. These characteristics
      probably reflect the adapting strategy of the bacteria that S. oneidensis
      represents to thrive in redox-stratified microaerobic and anaerobic environments.

PMID- 29367340
TI  - Purification and functional characterization of the vacuolar malate transporter
      tDT from Arabidopsis.
AB  - The exact transport characteristics of the vacuolar dicarboxylate transporter tDT
      from Arabidopsis are elusive. To overcome this limitation, we combined a range of
      experimental approaches comprising generation/analysis of tDT overexpressors,
      13CO2 feeding and quantification of 13C enrichment, functional characterization
      of tDT in proteoliposomes, and electrophysiological studies on vacuoles. tdt
      knockout plants showed decreased malate and increased citrate concentrations in
      leaves during the diurnal light-dark rhythm and after onset of drought, when
      compared with wildtypes. Interestingly, under the latter two conditions, tDT
      overexpressors exhibited malate and citrate levels opposite to tdt knockout
      plants. Highly purified tDT protein transports malate and citrate in a 1:1
      antiport mode. The apparent affinity for malate decreased with decreasing pH,
      whereas citrate affinity increased. This observation indicates that tDT exhibits
      a preference for dianion substrates, which is supported by electrophysiological
      analysis on intact vacuoles. tDT also accepts fumarate and succinate as
      substrates, but not alpha-ketoglutarate, gluconate, sulfate, or phosphate. Taking
      tDT as an example, we demonstrated that it is possible to reconstitute a vacuolar
      metabolite transporter functionally in proteoliposomes. The displayed, so far
      unknown counterexchange properties of tDT now explain the frequently observed
      reciprocal concentration changes of malate and citrate in leaves from various
      plant species. tDT from Arabidopsis is the first member of the well-known and
      widely present SLC13 group of carrier proteins, exhibiting an antiport mode of
      transport.

PMID- 29367342
TI  - GSE1 predicts poor survival outcome in gastric cancer patients by SLC7A5
      enhancement of tumor growth and metastasis.
AB  - Gastric cancer remains a malignancy with poor survival outcome. We herein report
      that GSE1, a proline-rich protein, possesses a role in the progression of human
      gastric cancer. The expression of GSE1 was observed to be much higher in human
      gastric cancer tissues compared with normal gastric tissues, and GSE1 expression
      correlated positively with lymph node metastasis, histological grade, depth of
      invasion, and clinical stage in gastric cancer patients. Moreover, GSE1
      expression was also associated with decreased post-operative relapse-free
      survival and overall survival in the cohort. The forced expression of GSE1 in
      gastric cancer cell lines resulted in increased cell proliferation, increased
      colony formation, enhanced cell migration, and invasion. Furthermore, forced
      expression of GSE1 also increased tumor size and enhanced lung metastasis in
      xenograft models. The depletion of endogenous GSE1 with shRNAs decreased the
      oncogenicity and invasiveness of gastric cancer cells both in vitro and in vivo
      In addition, GSE1 was determined to be a direct target of miR-200b and miR-200c.
      Furthermore, GSE1 positively regulated the downstream gene SLC7A5 (also known as
      LAT-1), which was scanned and verified from mRNA sequencing. GSE1 therefore
      possesses an oncogenic role in human gastric cancer, and targeted therapeutic
      approaches to inhibit GSE1 function in gastric cancer warrant further
      consideration.

PMID- 29367343
TI  - Why governments cannot afford Codentify to support their track and trace
      solutions.
AB  - BACKGROUND: In anticipation of the Protocol to Eliminate Illicit Trade in Tobacco
      Products (ITP) entering into force in 2018, there is a growing demand for
      information on track and trace (T&T) solutions for tobacco products. This article
      contrasts the efficacy of Codentify from the perspective of authentication with
      that of material-based multilayered security technologies. METHOD: To calculate
      the probability of detecting one fraudulent pack under Codentify, we relied on a
      modified Bernoulli trial experiment with independent repeated sampling without
      replenishment. The probability is calculated using a multinomial distribution
      formula adjusted for the fact that both legitimate and non-legitimate packs may
      be sold in the market. RESULTS: In a relatively small market, a law enforcement
      authority would have to inspect over 27 000 (almost 31 000) packs per week to
      have a 90% (95%) certainty that it did not miss a fraudulent pack under the
      Codentify system. A material based T&T solution would require only 45 (59) pack
      inspections a week to have the same level of confidence. CONCLUSIONS: This study
      demonstrates the inefficiency of Codentify compared to other solutions that
      incorporate material-based security features. Signatories to the ITP should
      reject Codentify due to both its low efficacy and its clear violation of the
      ITP's requirement that T&T shall not be performed by or delegated to the tobacco
      industry or its front groups.

PMID- 29367344
TI  - Erratum for the Research Article: "Single-cut genome editing restores dystrophin
      expression in a new mouse model of muscular dystrophy" by L. Amoasii, C. Long, H.
      Li, A. A. Mireault, J. M. Shelton, E. Sanchez-Ortiz, J. R. McAnally, S.
      Bhattacharyya, F. Schmidt, D. Grimm, S. D. Hauschka, R. Bassel-Duby, E. N. Olson.

PMID- 29367345
TI  - Dimethyl fumarate potentiates oncolytic virotherapy through NF-kappaB inhibition.
AB  - Resistance to oncolytic virotherapy is frequently associated with failure of
      tumor cells to get infected by the virus. Dimethyl fumarate (DMF), a common
      treatment for psoriasis and multiple sclerosis, also has anticancer properties.
      We show that DMF and various fumaric and maleic acid esters (FMAEs) enhance viral
      infection of cancer cell lines as well as human tumor biopsies with several
      oncolytic viruses (OVs), improving therapeutic outcomes in resistant syngeneic
      and xenograft tumor models. This results in durable responses, even in models
      otherwise refractory to OV and drug monotherapies. The ability of DMF to enhance
      viral spread results from its ability to inhibit type I interferon (IFN)
      production and response, which is associated with its blockade of nuclear
      translocation of the transcription factor nuclear factor kappaB (NF-kappaB). This
      study demonstrates that unconventional application of U.S. Food and Drug
      Administration-approved drugs and biological agents can result in improved
      anticancer therapeutic outcomes.

PMID- 29367347
TI  - Miniaturized neural system for chronic, local intracerebral drug delivery.
AB  - Recent advances in medications for neurodegenerative disorders are expanding
      opportunities for improving the debilitating symptoms suffered by patients.
      Existing pharmacologic treatments, however, often rely on systemic drug
      administration, which result in broad drug distribution and consequent increased
      risk for toxicity. Given that many key neural circuitries have sub-cubic
      millimeter volumes and cell-specific characteristics, small-volume drug
      administration into affected brain areas with minimal diffusion and leakage is
      essential. We report the development of an implantable, remotely controllable,
      miniaturized neural drug delivery system permitting dynamic adjustment of therapy
      with pinpoint spatial accuracy. We demonstrate that this device can chemically
      modulate local neuronal activity in small (rodent) and large (nonhuman primate)
      animal models, while simultaneously allowing the recording of neural activity to
      enable feedback control.

PMID- 29367346
TI  - Genetically modified lentiviruses that preserve microvascular function protect
      against late radiation damage in normal tissues.
AB  - Improvements in cancer survival mean that long-term toxicities, which contribute
      to the morbidity of cancer survivorship, are being increasingly recognized. Late
      adverse effects (LAEs) in normal tissues after radiotherapy (RT) are
      characterized by vascular dysfunction and fibrosis causing volume loss and tissue
      contracture, for example, in the free flaps used for immediate breast
      reconstruction after mastectomy. We evaluated the efficacy of lentivirally
      delivered superoxide dismutase 2 (SOD2) overexpression and connective tissue
      growth factor (CTGF) knockdown by short hairpin RNA in reducing the severity of
      LAEs in an animal model of free flap LAEs. Vectors were delivered by intra
      arterial injection, ex vivo, to target the vascular compartment. LVSOD2 and
      LVshCTGF monotherapy before irradiation resulted in preservation of flap volume
      or reduction in skin contracture, respectively. Flaps transduced with combination
      therapy experienced improvements in both volume loss and skin contracture. Both
      therapies reduced the fibrotic burden after irradiation. LAEs were associated
      with impaired vascular perfusion, loss of endothelial permeability, and stromal
      hypoxia, which were all reversed in the treatment model. Using a tumor recurrence
      model, we showed that SOD2 overexpression in normal tissues did not compromise
      the efficacy of RT against tumor cells but appeared to enhance it. LVSOD2 and
      LVshCTGF combination therapy by targeted, intravascular delivery reduced LAE
      severities in normal tissues without compromising the efficacy of RT and warrants
      translational evaluation as a free flap-targeted gene therapy.

PMID- 29367349
TI  - "Where there is life, there is hope".

PMID- 29367348
TI  - Integrin alpha4beta7 expression on peripheral blood CD4+ T cells predicts HIV
      acquisition and disease progression outcomes.
AB  - The gastrointestinal (GI) mucosa is central to HIV pathogenesis, and the integrin
      alpha4beta7 promotes the homing of immune cells to this site, including those
      that serve as viral targets. Data from simian immunodeficiency virus (SIV) animal
      models suggest that alpha4beta7 blockade provides prophylactic and therapeutic
      benefits. We show that pre-HIV infection frequencies of alpha4beta7+ peripheral
      blood CD4+ T cells, independent of other T cell phenotypes and genital
      inflammation, were associated with increased rates of HIV acquisition in South
      African women. A similar acquisition effect was observed in a Kenyan cohort and
      in nonhuman primates (NHPs) after intravaginal SIV challenge. This association
      was stronger when infection was caused by HIV strains containing V2 envelope
      motifs with a preference for alpha4beta7 binding. In addition, pre-HIV
      alpha4beta7+ CD4+ T cells predicted a higher set-point viral load and a greater
      than twofold increased rate of CD4+ T cell decline. These results were confirmed
      in SIV-infected NHPs. Increased frequencies of pre-HIV alpha4beta7+ CD4+ T cells
      were also associated with higher postinfection expression of lipopolysaccharide
      binding protein, a microbial translocation marker, suggestive of more extensive
      gut damage. CD4+ T cells expressing alpha4beta7 were rapidly depleted very early
      in HIV infection, particularly from the GI mucosa, and were not restored by early
      antiretroviral therapy. This study provides a link between alpha4beta7 expression
      and HIV clinical outcomes in humans, in line with observations made in NHPs.
      Given the availability of a clinically approved anti-alpha4beta7 monoclonal
      antibody for treatment of inflammatory bowel disease, these data support further
      evaluation of targeting alpha4beta7 integrin as a clinical intervention during
      HIV infection.

PMID- 29367350
TI  - Are changes in objective working hour characteristics associated with changes in
      work-life conflict among hospital employees working shifts? A 7-year follow-up.
AB  - OBJECTIVE: To investigate whether changes in objective working hour
      characteristics are associated with parallel changes in work-life conflict (WLC)
      among hospital employees. METHODS: Survey responses from three waves of the
      Finnish Public Sector study (2008, 2012 and 2015) were combined with payroll data
      from 91 days preceding the surveys (n=2 482, 93% women). Time-dependent fixed
      effects regression models adjusted for marital status, number of children and
      stressfulness of the life situation were used to investigate whether changes in
      working hour characteristics were associated with parallel change in WLC. The
      working hour characteristics were dichotomised with cut-points in less than or
      greater than 10% or less than or greater than25% occurrence) and WLC to frequent
      versus seldom/none. RESULTS: Change in proportion of evening and night shifts and
      weekend work was significantly associated with parallel change in WLC (adjusted
      OR 2.19, 95% CI 1.62 to 2.96; OR 1.71, 95% CI 1.21 to 2.44; OR 1.63, 95% CI 1.194
      to 2.22, respectively). Similarly, increase or decrease in proportion of quick
      returns (adjusted OR 1.45, 95% CI 1.10 to 1.89) and long work weeks (adjusted OR
      1.26, 95% CI 1.04 to 1.52) was associated with parallel increase or decrease in
      WLC. Single days off and very long work weeks showed no association with WLC.
      CONCLUSIONS: Changes in unsocial working hour characteristics, especially in
      connection with evening shifts, are consistently associated with parallel changes
      in WLC.

PMID- 29367351
TI  - Deleting the IF1-like zeta subunit from Paracoccus denitrificans ATP synthase is
      not sufficient to activate ATP hydrolysis.
AB  - In oxidative phosphorylation, ATP synthases interconvert two forms of free
      energy: they are driven by the proton-motive force across an energy-transducing
      membrane to synthesize ATP and displace the ADP/ATP ratio from equilibrium. For
      thermodynamically efficient energy conversion they must be reversible catalysts.
      However, in many species ATP synthases are unidirectional catalysts (their rates
      of ATP hydrolysis are negligible), and in others mechanisms have evolved to
      regulate or minimize hydrolysis. Unidirectional catalysis by Paracoccus
      denitrificans ATP synthase has been attributed to its unique zeta subunit, which
      is structurally analogous to the mammalian inhibitor protein IF1 Here, we used
      homologous recombination to delete the zeta subunit from the P. denitrificans
      genome, and compared ATP synthesis and hydrolysis by the wild-type and knockout
      enzymes in inverted membrane vesicles and the F1-ATPase subcomplex. ATP synthesis
      was not affected by loss of the zeta subunit, and the rate of ATP hydrolysis
      increased by less than twofold, remaining negligible in comparison with the rates
      of the Escherichia coli and mammalian enzymes. Therefore, deleting the P.
      denitrificans zeta subunit is not sufficient to activate ATP hydrolysis. We close
      by considering our conclusions in the light of reversible catalysis and
      regulation in ATP synthase enzymes.

PMID- 29367352
TI  - Seeding of proteins into amyloid structures by metabolite assemblies may clarify
      certain unexplained epidemiological associations.
AB  - The accumulation of various metabolites appears to be associated with diverse
      human diseases. However, the aetiological link between metabolic alteration and
      the observed diseases is still elusive. This includes the correlation between the
      abnormally high levels of homocysteine and quinolinic acid in Alzheimer's
      disease, as well as the accumulation of oncometabolites in malignant processes.
      Here, we suggest and discuss a possible mechanistic insight into metabolite
      accumulation in conditions such as neurodegenerative diseases and cancer. Our
      hypothesis is based on the demonstrated ability of metabolites to form amyloid
      like structures in inborn error of metabolism disorders and the potential of such
      metabolite amyloids to promote protein aggregation. This notion can provide a new
      paradigm for neurodegeneration and cancer, as both conditions were linked to loss
      of function due to protein aggregation. Similar to the well-established
      observation of amyloid formation in many degenerative disorders, the formation of
      amyloids by tumour-suppressor proteins, including p53, was demonstrated in
      malignant states. Moreover, this new paradigm could fill the gap in understanding
      the high occurrence of specific types of cancer among genetic error of metabolism
      patients. This hypothesis offers a fresh view on the aetiology of some of the
      most abundant human maladies and may redirect the efforts towards new therapeutic
      developments.

PMID- 29367354
TI  - The Harvey experiments.

PMID- 29367353
TI  - Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE
      and NRZ interactions.
AB  - Lipid incorporation from endoplasmic reticulum (ER) to lipid droplet (LD) is
      important in controlling LD growth and intracellular lipid homeostasis. However,
      the molecular link mediating ER and LD cross talk remains elusive. Here, we
      identified Rab18 as an important Rab guanosine triphosphatase in controlling LD
      growth and maturation. Rab18 deficiency resulted in a drastically reduced number
      of mature LDs and decreased lipid storage, and was accompanied by increased ER
      stress. Rab3GAP1/2, the GEF of Rab18, promoted LD growth by activating and
      targeting Rab18 to LDs. LD-associated Rab18 bound specifically to the ER
      associated NAG-RINT1-ZW10 (NRZ) tethering complex and their associated SNAREs
      (Syntaxin18, Use1, BNIP1), resulting in the recruitment of ER to LD and the
      formation of direct ER-LD contact. Cells with defects in the NRZ/SNARE complex
      function showed reduced LD growth and lipid storage. Overall, our data reveal
      that the Rab18-NRZ-SNARE complex is critical protein machinery for tethering ER
      LD and establishing ER-LD contact to promote LD growth.

PMID- 29367355
TI  - Hair loss is an important symptom of the menopause.

PMID- 29367356
TI  - Multiple anomalies in the origin and course of vertebral arteries and aberrant
      right subclavian artery in a child with moyamoya syndrome.
AB  - Here we report, for the first time, a combination of five-vessel aortic arch,
      anomalous origin of the right vertebral artery (VA) from the common carotid
      artery (CCA), an aberrant right subclavian artery (SCA), and bilateral
      symmetrical segmental agenesis of VAs.In this case report, we present a patient
      with moyamoya syndrome (MMS) and Down syndrome (DS) who has bilateral symmetrical
      segmental agenesis of VAs, left VA originating from aortic arch and anomalous
      origin of right VA arising from CCA in combination with an aberrant right SCA.
      Therefore, five vessels are originating from aortic arch. Here, we report, for
      the first time, a combination of five-vessel aortic arch with an aberrant right
      SCA and symmetrical segmental agenesis of both VAs. The possible embryological
      mechanisms of the anomalies as well as an relation with MMS and DS are discussed.

PMID- 29367357
TI  - Seesawing end-tidal carbon dioxide: portent of critical carbon dioxide embolism
      in retroperitoneoscopy.
AB  - An abrupt increase in end-tidal CO2 (EtCO2; from 35 to 58 mm Hg) followed by a
      sudden fall (to 18 mm Hg) was noted during retroperitoneoscopic adrenalectomy
      under general anaesthesia in a 23-year-old patient with adrenal hyperplasia. This
      was accompanied by hypotension (systolic blood pressure of 60 mm Hg),
      desaturation (88% SpO2) and ST depression (3.5 mm). The patient was resuscitated
      with fluids and vasopressor drugs and about 4 mL of air was aspirated through the
      central venous catheter, confirming the diagnosis of an intraoperative gas
      embolism. Later, a rent in the adrenal vein extending into the inferior vena cava
      was discovered and sutured. The blood pressure, EtCO2, ST segment and pulse
      oximetry returned to normal after 15 min. This case demonstrates that gas
      embolism may transpire during retroperitoneoscopic adrenalectomy and an acute
      rise followed by a sharp fall in EtCO2 should alert the anaesthesiologist to this
      rare but potentially fatal complication.

PMID- 29367358
TI  - Recurrent migration of peripherally inserted central catheter into the azygos
      vein.
AB  - Peripherally inserted central catheter (PICC) migration into azygos vein (AV) is
      a rare complication. It is recognised only when catheter malfunction occurs or
      when patients develop associated complications. PICC migration into AV has been
      reported to be associated with various complications such as catheter
      malfunction, perforation, haemorrhage, thrombosis, infection and stenosis of AV.
      Pleural effusion and trachea-azygos fistulas have also been reported. We present
      a patient with recurrent migration of PICC into AV after an initial corrective
      repositioning during the same hospital stay. In this case, PICC migration was
      possibly related to left-sided approach, use of smaller diameter PICC, severe
      congestive heart failure and her bedbound status. PICC migration should be
      considered when PICC found be malfunctioning, especially if associated with the
      above risk factors.

PMID- 29367359
TI  - Illegal immigration: the puzzling role of several risk factors for
      rhabdomyolysis.
AB  - A 14-year-old boy presented with low-grade fever, widespread myalgia and
      difficulty in walking and standing 2 days after the undocumented trip which
      brought him from western Africa to Italy. His serum creatine phosphokinase was
      markedly elevated. He was diagnosed with rhabdomyolysis and was volume-restored
      with normal saline and bicarbonate-containing fluid. Anamnesis revealed illegal,
      not well-specified, forced consumption in his fatherland, and very bad conditions
      of the trip (prolonged immobility, dehydration, hypothermia). Workup included a
      respiratory microbiological panel which was positive for Chlamydia pneumoniae
      Other microbiological agents were excluded. After 3 weeks, he recovered complete
      motility. Undocumented immigrants may present several risk factors for
      rhabdomyolysis that give to this group of individuals a higher risk of developing
      this disorder.

PMID- 29367360
TI  - Recurrence of Graves' disease in ectopic thyroid tissue.
AB  - A 40-year-old woman with a history of Graves' disease status postorbital
      decompression for severe ophthalmopathy underwent total thyroidectomy by a high
      volume thyroid surgeon in July 2013 with a benign final pathology. Eight months
      later, she presented with a mass on the right anterior neck that showed minimal
      growth over time. Her thyroid stimulating immunoglobulin and thyroid-stimulating
      hormone receptor antibody levels were consistently elevated and increasing. She
      underwent removal of the neck mass in September 2016. Final pathology showed
      benign thyroid tissue with diffuse hyperplasia and lymphoid follicles, consistent
      with Graves' disease. We present an unusual recurrence of Graves' disease post
      total thyroidectomy that recurred secondary to ectopic thyroid tissue in the
      right upper anterior neck deep to the strap muscles.

PMID- 29367361
TI  - Twenty years of biological therapy in an patient with IBD.
AB  - This interesting case is the first to our knowledge to report outcomes of a
      patient with Crohn's disease (CD) treated with the biological drug, infliximab,
      for around 20 years. The case highlights the positive effect of long-term use of
      infliximab in achieving and maintaining remission in a patient with CD.In this
      case, loss of response to infliximab was not dependent on length of exposure to
      the drug. It also appeared that infliximab was still efficacious after drug
      holidays, which can be especially important around times of pregnancy. Of
      interest, 'loss of response' to infliximab occurred at one particular time point.
      The drug was then reintroduced at a later date, which gave the patient clinical
      benefit. This case suggests that in some situations infliximab can be
      reintroduced in patients with previous 'loss of response'.Importantly, in this
      case, Infliximab had no major adverse effects during the 20 years follow-up.

PMID- 29367362
TI  - Primary meningococcal arthritis as a presentation of nodal marginal zone
      lymphoma.
AB  - A 68-year-old man presented with a 4-day history of worsening knee and arm pain.
      On examination, there was erythema and swelling of the left knee and both wrists.
      Joint aspiration grew Neisseria meningitidis Blood tests showed an unusually high
      total protein level (100 g/L) and an IgM kappa paraprotein band of 45 g/L on
      protein electrophoresis. CT showed widespread lymphadenopathy, hepatosplenomegaly
      and multilevel thoracic vertebral collapse. A bone marrow biopsy revealed a
      lymphoplasmacytic infiltrate and a lymph node biopsy showed features of nodal
      marginal zone lymphoma with plasmacytic differentiation.

PMID- 29367364
TI  - Unusual case of hemidiaphragmatic paralysis secondary to cervical herpes zoster.
AB  - Hemidiaphragmatic paralysis is usually caused by surgery, malignancy or trauma
      and rarely by viral infections. Herpes zoster (shingles) results in varied
      neurological complications, but peripheral motor involvement or diaphragmatic
      paralysis is rare. We report the case of an 87-year-old male who presented with
      worsening breathlessness soon after an episode of shingles, affecting his right
      neck and upper chest. He had no alarm symptoms, history of trauma or malignancy.
      Skin lesions resolved after a few weeks, but his breathing did not improve. Chest
      X-ray revealed a new finding of elevated right hemidiaphragm; diaphragmatic
      ultrasound confirmed paradoxical cranial movement of right hemidiaphragm on sniff
      testing. CT scan showed no lung mass and complete collapse of right lower lobe
      due to elevated right hemidiaphragm. Patient has required no treatment and is
      under regular follow-up with the ventilation clinic.

PMID- 29367363
TI  - Bony swellings: an enigma.

PMID- 29367365
TI  - Case of acute mixed liver injury due to hypothyroidism.
AB  - The effects of hypothyroidism on the liver are not well understood. A 77-year-old
      woman with Hashimoto's thyroiditis had stopped taking levothyroxine on her own
      for 6 months. Her thyroid stimulating hormone (TSH) level was consistent with
      severe hypothyroidism. She resumed thyroid replacement therapy. The following
      month, her liver function tests were significantly elevated. Seven weeks after
      resumption of therapy, her TSH and liver tests had returned to normal. We
      attribute the mixed hepatocellular injury to hypothyroidism that resolved on
      correction of the hypothyroid state. This case reminds us that thyroid disease
      should be considered when evaluating acute liver injury.

PMID- 29367366
TI  - Rothmund-Thomson syndrome (RTS) with osteosarcoma due to RECQL4 mutation.
AB  - Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder with
      clinical features consisting of poikiloderma, skeletal abnormalities, sparse
      hair, absent or scanty eyelashes and eyebrows and short stature. Patients with
      RTS due to genetic mutations of RECQL4 genes carry a high risk of developing
      osteosarcoma during childhood. Because of this, early genetic diagnosis is
      important. Here, we describe a 14-year-old white boy who developed an
      erythematous rash on both cheeks before the age of 3 months and was noted to have
      absent eyelashes and scanty eyebrows. He was found to have compound heterozygous
      mutations of the RECQL4 gene alleles at the age of 6 months and was diagnosed to
      have RTS type II. He subsequently developed osteosarcoma at age 10 which was
      successfully treated, and currently he has been tumour free for over 3 years.

PMID- 29367367
TI  - Dual mobility total hip dislocation-femoral stem loosening while attempting
      closed reduction: a cautionary note.
AB  - A 77-year-old man sustained an acetabular fracture after falling from a staircase
      and landing on his right side. He fractured the anterior column of his acetabulum
      and the quadrilateral plate. He underwent a single-stage open reduction and
      internal fixation of the fracture combined with a dual mobility total hip
      arthroplasty (THA). He sustained a traumatic hip dislocation 1 month
      postoperatively. Closed reduction was attempted at another hospital, and the
      femoral stem was pulled out. We believe this was caused by the polyliner being
      hitched either to the acetabular cup or in the soft tissues around the ilium. We
      present this case to caution orthopaedic surgeons that dual mobility THA
      dislocations are difficult to diagnose as the polyliner is not clearly seen on X
      rays, and reduction attempts may lead to worsening of an already difficult
      situation.

PMID- 29367368
TI  - Lamotrigine-induced drug reaction with eosinophilia and systemic symptoms (DRESS)
      during primary Epstein-Barr virus (EBV) infection.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe,
      potentially life-threatening idiosyncratic drug reaction that may result in skin
      eruption, mucous membrane involvement, eosinophilia, atypical lymphocytosis and
      lymphadenopathy, with wide-ranging internal organ involvement. The authors report
      the case of a 21-year-old man who was prescribed lamotrigine for anxiety
      disorder. After 2 weeks of treatment, he developed a pruritic morbilliform rash
      on his trunk and upper extremities that was associated with fever, sore throat,
      bilateral scleral injection, nausea, vomiting and abdominal pain. A laboratory
      work-up revealed elevated transaminases and atypical lymphocytosis. He was found
      to have an active Epstein-Barr virus infection. Lamotrigine was discontinued due
      to suspicion of DRESS; the patient received pulsed intravenous methylprednisolone
      followed by oral prednisone taper, which resulted in a significant improvement of
      symptoms. At follow-up 3 weeks later, signs and symptoms had completely resolved.
      Follow-up laboratory tests revealed that liver dysfunction had normalised.

PMID- 29367369
TI  - Optimal approach to assessing T-cell function in haematopoietic cell transplant
      recipients.
AB  - Standardised approaches to functional immune assessment after haematopoietic cell
      transplantation (HCT) are lacking. A 12-year-old girl with relapsed acute
      myelogenous leukaemia, 2 years post-unrelated HCT, underwent immunological
      evaluation prior to receiving live vaccinations. Assessment of standard immune
      parameters and T-cell proliferation to phytohaemagglutinin was reassuring. She
      was given Varicella vaccination based on usual post-transplant protocols but was
      hospitalised 10 days later with localised Varicella infection (vaccine strain).
      Following recovery, she underwent further assessment that showed reduced T-cell
      proliferation to an anti-CD3 stimulation panel (anti-CD3 alone, soluble anti-CD3+
      anti-CD28 and soluble anti-CD3+ plus exogenous IL-2). On reassessment, 7 months
      later, T-cell responses to anti-CD3 stimulation were normal and she was
      revaccinated without further incident. Measurement of T-cell proliferation to
      anti-CD3 stimulants likely yields more useful information about global T-cell
      function and should be strongly considered prior to live vaccine administration
      post-allogeneic haematopoietic transplant.

PMID- 29367370
TI  - Endometriosis presenting as a vaginal mass.
AB  - A 43-year-old woman with an anterior vaginal wall mass was referred to
      gynaecology outpatient for diagnosis and management. Clinical assessment was
      indicative of a urethral diverticulum, however MRI and ultrasound imaging
      suggested a Gartner's duct cyst. Following excision of the lesion, histology
      revealed evidence of an endometriotic cyst. The patient had no other symptoms of
      endometriosis and remained asymptomatic 3 months following excision. This case
      highlights the widespread locations in which endometrial tissue can be found, and
      therefore the range of symptomatology. This in turn lends itself to diagnostic
      difficulty without histological confirmation.

PMID- 29367371
TI  - Non-ionic iodinated contrast-induced sialadenitis with parotid gland sparing in
      patient of hepatocellular carcinoma.
AB  - 61-years-old male patient presented with complain of neck swelling and soreness
      following contrast-enhanced (CE) CT examination with resolution of symptoms in 36
      48 hours. He is diagnosed with hepatitis C virus and hepatocellular carcinoma
      (HCC); already treated with radiofrequency ablation for HCC. He had already
      undergone two CECT examinations before he was referred to our institution for
      disease staging/treatment. He also underwent three triphasic CT scan examinations
      at our institution during the course of treatment for treatment response and
      staging. Patient remained undiagnosed up to his fourth CT scan due to inability
      to relate symptoms with contrast administration. The patient was offered close
      monitoring on fifth CT exam and ultrasound of neck revealed enlarged and
      echogenic bilateral submandibular glands, however, thyroid and bilateral parotid
      glands appear unremarkable. This represents transient iodinated contrast induced
      sialadenitis with sparing of parotid glands.

PMID- 29367372
TI  - Doxycycline sclerotherapy for post-traumatic inguinal lymphocele in a child.
AB  - Lymphoceles are abnormal collections of lymphatic fluid caused by a disruption in
      the lymphatic channels and leakage of lymph. This most commonly occurs after
      surgical procedures, but occasionally lymphoceles may be the result of trauma,
      more commonly penetrating trauma. Lymphoceles resulting from blunt trauma are
      rare in both adults and children. In the adult population, there are few
      published case reports, and management principles vary. To date, there are no
      reports of traumatic lymphoceles in the paediatric population, and therefore
      there is no precedent for treatment. Here, we report the case of a young boy who
      developed an inguinal lymphocele from a bicycle handle bar injury which was
      successfully treated with doxycycline sclerotherapy.

PMID- 29367373
TI  - Extensive skin ulcers in a child with juvenile dermatomyositis.
AB  - Juvenile dermatomyositis (JDM) is a multisystemic disorder. Vasculitic ulcers in
      JDM have been reported to involve axilla, elbow or extensor surfaces of other
      joints. We report a young boy with JDM who presented with extensive cutaneous
      ulcers involving scrotum, prepuce, gluteal region, neck, bilateral axilla,
      periumbilical area and bilateral elbows and popliteal fossa. His disease course
      was marked by several relapses and he required immunosuppression with
      prednisolone, subcutaneous methotrexate and intravenous cyclophosphamide. His
      muscle weakness improved and skin ulcers healed after 6 months of intensive
      immunosuppressive therapy. Children with JDM and ulcers often show increased
      resistance to immunosuppressive therapy. Extensive cutaneous ulcers in JDM,
      especially those involving the scrotum, have never been described. Awareness
      regarding the uncommon manifestations is important to guide appropriate therapy.

PMID- 29367374
TI  - Intracranial myopericytoma: a tumour in a rare location.
AB  - A 49-year-old female with history of headache, nausea and vomiting with some
      weeks of evolution, without neurological symptoms. Radiology revealed an
      expansive lesion near the inferior vermix and cerebellar tonsils, with
      heterogeneous gadolinium uptake and mass effect on the fourth ventricle,
      representing a probable extraventricular origin for the lesion. Pathological
      examination showed a proliferation of oval/spindle cell proliferation with
      eosinophil cytoplasm and small and monotonous nuclei, without mitoses. The cells
      had a concentric growth, surrounding thin-walled blood vessels with foci of
      stromal myxoid degeneration and whorled pattern. The vessels had a
      haemangiopericytoma pattern and were lined by non-atypical endothelial cells. The
      tumorous cells expressed vimentin, alpha-smooth actin and heavy-chain caldesmon
      and were negative for epithelial membrane antigen, protein S100, HMB45, CD34,
      calponin and desmin, thus providing the final diagnosis of intracranial
      myopericytoma.

PMID- 29367375
TI  - Delayed presentation of a virilising, pure testosterone-secreting adrenocortical
      carcinoma with coexistent composite myelolipoma and a venous thrombus extending
      to the heart.
AB  - A 40-year-old normotensive woman presented with abnormal facial hair for 4 years
      and amenorrhoea for 13 years. Hormonal, biochemical and haematological evaluation
      showed isolated elevation of serum testosterone and free testosterone. Her
      follicle-stimulating hormone and luteinising hormone were in the premenopausal
      range. Until recently she had reconciled to early 'menopause' and visited beauty
      clinics but never sought medical evaluation. Imaging revealed an enhancing left
      adrenal mass with fat densities and venous thrombus extending through the
      inferior vena cava to a 7 cm mass in the right atrium. She underwent left kidney
      preserving surgery utilising hypothermic cardiopulmonary bypass with early
      clamping of the pulmonary artery without circulatory arrest. Histology showed
      adrenocortical carcinoma with composite incidental myelolipoma and neoplastic
      thrombus. At 2 months, testosterone has normalised and she is doing well.
      Isolated testosterone-secreting adrenocortical carcinoma with massive venous
      thrombus is rare as is coincidental composite macroscopic myelolipoma.

PMID- 29367377
TI  - Cranial neuropathy and severe pain due to early disseminated Borrelia burgdorferi
      infection.
AB  - A 61-year-old man presented to the emergency department in the summer with a
      right seventh cranial nerve lower motor neuron palsy and worsening paraesthesias
      for 6 weeks. He had debilitating pain at the scalp and spine. Prior work up was
      unrevealing. The patient resided in the upper Midwest region of the USA and
      worked outdoors, optimising the landscape for white tailed deer. Repeat
      cerebrospinal fluid testing revealed a lymphocytic pleocytosis and positive IgM
      Lyme serology. Brain MRI demonstrated enhancement of multiple cranial nerves
      bilaterally. He was diagnosed with early Lyme neuroborreliosis and treated with
      28 days of intravenous ceftriaxone. While the painful meningoradiculitis, also
      known as Bannwarth syndrome, is more commonly seen in Europe, facial palsy is
      more frequently encountered in the USA. Clinical manifestations of
      neuroborreliosis are important to recognise as the classic presentation varies by
      geography and on occasion repeat serological testing may be necessary.

PMID- 29367376
TI  - New drugs and new toxicities: pembrolizumab-induced myocarditis.
AB  - Pembrolizumab is an immune checkpoint inhibitor that significantly improves
      clinical outcomes in numerous solid organ malignancies. Despite successful
      therapeutic responses, this new drug comes with a constellation of adverse
      reactions. Herein, we chronicle the case of a patient with metastatic non-small
      cell lung cancer treated with pembrolizumab. After two cycles, he developed new
      onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with
      diffuse ST-segment elevations. Echocardiography revealed severe biventricular
      cardiac dysfunction. Based on diagnostic workup and exclusion of probable
      aetiologies, the patient was diagnosed with pembrolizumab-induced myocarditis.
      The treatment was initiated with corticosteroids and guideline-conform heart
      failure therapy. He demonstrated a marked clinical response with resolution of
      congestive heart failure symptoms. This article summarises the clinical evidence
      regarding the epidemiology, pathophysiology, clinical features, diagnostic
      modalities and management of patients with pembrolizumab-associated myocarditis.
      In addition, it highlights that programmed death receptor-1 inhibition can cause
      a spectrum of autoimmune adverse events requiring clinical monitoring and
      periodic screenings.

PMID- 29367378
TI  - Combination drug chemotherapy and massive skeletal allograft in the management of
      hydatid disease of femur.
AB  - Hydatid disease of long bone is a rare presentation. Chemotherapy and surgery
      constitute the standard treatment of choice. Non-union of a pathological fracture
      of femur particularly due to hydatid disease has been known to be resistant to
      treatment. These resistant cases require combination drug chemotherapy and
      excision of the lesion. Reconstruction of a large skeletal defect following
      resection of the lesion poses a challenge to the orthopaedic surgeons. We discuss
      the staged treatment of hydatid disease of shaft of femur with resection and
      cement spacer application followed by reconstruction using massive skeletal
      allograft under cover of combination drug chemotherapy.

PMID- 29367379
TI  - Rare presentation of AICA syndrome.
AB  - We report a rare presentation of an anterior inferior cerebellar artery (AICA)
      infarct in a 74-year-old woman with acute-onset nausea, vomiting, vertigo and
      gait instability long before the full onset of symptoms and a negative MRI on
      admission. Over the next several days the patient developed left facial weakness,
      numbness, hypoacusis, and limb and gait ataxia, and was found to have acute
      infarcts of the left pons and cerebellar peduncle consistent with an AICA
      syndrome. We discuss this rare stepwise presentation in AICA syndrome and
      possible underlying pathophysiology. Such patients at risk for cerebrovascular
      disease should undergo a careful history, exam and follow-up, even with negative
      MRI findings, as their symptoms may precede a serious vascular event.

PMID- 29367380
TI  - Post-cholecystectomy partial biliary stricture leading to primary intrahepatic
      calculi.

PMID- 29367381
TI  - Fulminant myocarditis.

PMID- 29367383
TI  - Understanding Pulmonary Stress-Strain Relationships in Severe ARDS and Its
      Implications for Designing a Safer Approach to Setting the Ventilator.
AB  - This review describes the current understanding of the lungs' response to
      deforming stress under conditions of both normal physiology and acute lung
      injury. Several limiting assumptions are needed to infer lung parenchymal stress
      and strain from airway pressure, volume, and flow data from mechanically
      ventilated patients with injured lungs. These assumptions include the effects of
      the chest wall on lung-surface pressure, its topographical distribution, and the
      effects of non-uniform tissue properties on local parenchymal stresses. In
      addition, there is a spectrum of biophysical lung injury mechanisms that involves
      normal as well as tangential alveolar wall stresses. To these are added important
      secondary effects on pulmonary vascular resistance and right heart function.
      Understanding both the assumptions of lung mechanics and the scope of injury
      mechanisms operating during ARDS is necessary to interpret the results of
      clinical trials that inform prevailing ventilator-management guidelines. The
      implications issuing from these 3 topics inform a safer approach to setting and
      adjusting the ventilator to minimize the risk of ventilator-induced lung injury.
      This is enumerated in a 5-step approach that can be used to guide ventilator
      management of unstable patients with severe lung injury.

PMID- 29367382
TI  - GPR56/ADGRG1 regulates development and maintenance of peripheral myelin.
AB  - Myelin is a multilamellar sheath generated by specialized glia called Schwann
      cells (SCs) in the peripheral nervous system (PNS), which serves to protect and
      insulate axons for rapid neuronal signaling. In zebrafish and rodent models, we
      identify GPR56/ADGRG1 as a conserved regulator of PNS development and health. We
      demonstrate that, during SC development, GPR56-dependent RhoA signaling promotes
      timely radial sorting of axons. In the mature PNS, GPR56 is localized to distinct
      SC cytoplasmic domains, is required to establish proper myelin thickness, and
      facilitates organization of the myelin sheath. Furthermore, we define plectin-a
      scaffolding protein previously linked to SC domain organization, myelin
      maintenance, and a series of disorders termed "plectinopathies"-as a novel
      interacting partner of GPR56. Finally, we show that Gpr56 mutants develop
      progressive neuropathy-like symptoms, suggesting an underlying mechanism for
      peripheral defects in some human patients with GPR56 mutations. In sum, we define
      Gpr56 as a new regulator in the development and maintenance of peripheral myelin.

PMID- 29367384
TI  - Office Spirometry in Primary Care for the Diagnosis and Management of COPD:
      National Lung Health Education Program Update.
AB  - The use of office spirometry was recommended by the National Lung Health
      Education Program (NLHEP) consensus conference in 1999 for detection and
      management of COPD. Since that time, spirometry utilization has increased, but
      its role in the diagnosis of COPD is still evolving. This update reviews the role
      of spirometry for screening and case finding in COPD as well as for asthma.
      Spirometry has been used for disease management in patients with airway
      obstruction, with varying results. The diagnostic criteria for COPD using
      spirometry have also evolved in the past 17 years, with differences arising
      between the Global Initiative for Chronic Obstructive Lung Disease and NLHEP
      recommendations. More sophisticated spirometers as well as new reference
      equations are widely available. Standardization guidelines from the American
      Thoracic Society/European Respiratory Society published in 2005 provide a robust
      framework for performing and interpreting spirometry, but clinicians still need
      hands-on training and meaningful feedback to perform high-quality spirometry in
      the office setting.

PMID- 29367385
TI  - Pulmonary Rehabilitation House Calls.

PMID- 29367386
TI  - Expanding the Evidence for Aerosol Therapy During Noninvasive Ventilation.

PMID- 29367389
TI  - Masking of an auditory behaviour reveals how male mosquitoes use distortion to
      detect females.
AB  - The mating behaviour of many mosquito species is mediated essentially by sound:
      males follow and mate with a female mid-flight by detecting and tracking the
      whine of her flight-tones. The stereotypical rapid frequency modulation (RFM)
      male behaviour, initiated in response to the detection of the female's flight
      tones, has provided a means of investigating these auditory mechanisms while
      males are free-flying. Mosquitoes hear with their antennae, which vibrate to near
      field acoustic excitation. The antennae generate nonlinear vibrations (distortion
      products, DPs) at frequencies that are equal to the difference between the two
      simultaneously presented tones, e.g. the male and female flight-tones, which are
      detected by mechanoreceptors in the auditory Johnston's organ (JO) at the base of
      the antenna. Recent studies indicated the male mosquito's JO is tuned not to the
      female flight-tone, but to the frequency difference between the male and female
      flight-tones. To test the hypothesis that mosquitoes detect this frequency
      difference, Culex quinquefasciatus males were presented simultaneously with a
      female flight-tone and a masking tone, which should suppress the male's RFM
      response to sound. The free-flight behavioural and in vivo electrophysiological
      experiments revealed that acoustic masking suppresses the RFM response to the
      female's flight-tones by attenuating the DPs generated in the nonlinear vibration
      of the antennae. These findings provide direct evidence in support of the
      hypothesis that male mosquitoes detect females when both are in flight through
      difference tones generated in the vibrations of their antennae owing to the
      interaction between their own flight-tones and those of a female.

PMID- 29367388
TI  - Low cigarette consumption and risk of coronary heart disease and stroke: meta
      analysis of 141 cohort studies in 55 study reports.
AB  - OBJECTIVE: To use the relation between cigarette consumption and cardiovascular
      disease to quantify the risk of coronary heart disease and stroke for light
      smoking (one to five cigarettes/day). DESIGN: Systematic review and meta
      analysis. DATA SOURCES: Medline 1946 to May 2015, with manual searches of
      references. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective cohort
      studies with at least 50 events, reporting hazard ratios or relative risks (both
      hereafter referred to as relative risk) compared with never smokers or age
      specific incidence in relation to risk of coronary heart disease or stroke. DATA
      EXTRACTION/SYNTHESIS: MOOSE guidelines were followed. For each study, the
      relative risk was estimated for smoking one, five, or 20 cigarettes per day by
      using regression modelling between risk and cigarette consumption. Relative risks
      were adjusted for at least age and often additional confounders. The main measure
      was the excess relative risk for smoking one cigarette per day (RR1_per_day-1)
      expressed as a proportion of that for smoking 20 cigarettes per day (RR20_per_day
      1), expected to be about 5% assuming a linear relation between risk and
      consumption (as seen with lung cancer). The relative risks for one, five, and 20
      cigarettes per day were also pooled across all studies in a random effects meta
      analysis. Separate analyses were done for each combination of sex and disorder.
      RESULTS: The meta-analysis included 55 publications containing 141 cohort
      studies. Among men, the pooled relative risk for coronary heart disease was 1.48
      for smoking one cigarette per day and 2.04 for 20 cigarettes per day, using all
      studies, but 1.74 and 2.27 among studies in which the relative risk had been
      adjusted for multiple confounders. Among women, the pooled relative risks were
      1.57 and 2.84 for one and 20 cigarettes per day (or 2.19 and 3.95 using relative
      risks adjusted for multiple factors). Men who smoked one cigarette per day had
      46% of the excess relative risk for smoking 20 cigarettes per day (53% using
      relative risks adjusted for multiple factors), and women had 31% of the excess
      risk (38% using relative risks adjusted for multiple factors). For stroke, the
      pooled relative risks for men were 1.25 and 1.64 for smoking one or 20 cigarettes
      per day (1.30 and 1.56 using relative risks adjusted for multiple factors). In
      women, the pooled relative risks were 1.31 and 2.16 for smoking one or 20
      cigarettes per day (1.46 and 2.42 using relative risks adjusted for multiple
      factors). The excess risk for stroke associated with one cigarette per day (in
      relation to 20 cigarettes per day) was 41% for men and 34% for women (or 64% and
      36% using relative risks adjusted for multiple factors). Relative risks were
      generally higher among women than men. CONCLUSIONS: Smoking only about one
      cigarette per day carries a risk of developing coronary heart disease and stroke
      much greater than expected: around half that for people who smoke 20 per day. No
      safe level of smoking exists for cardiovascular disease. Smokers should aim to
      quit instead of cutting down to significantly reduce their risk of these two
      common major disorders.

PMID- 29367390
TI  - Native turncoats and indirect facilitation of species invasions.
AB  - At local scales, native species can resist invasion by feeding on and competing
      with would-be invasive species. However, this relationship tends to break down or
      reverse at larger scales. Here, we consider the role of native species as
      indirect facilitators of invasion and their potential role in this diversity
      driven 'invasion paradox'. We coin the term 'native turncoats' to describe native
      facilitators of non-native species and identify eight ways they may indirectly
      facilitate species invasion. Some are commonly documented, while others, such as
      indirect interactions within competitive communities, are largely undocumented in
      an invasion context. Therefore, we use models to evaluate the likelihood that
      these competitive interactions influence invasions. We find that native turncoat
      effects increase with the number of resources and native species. Furthermore,
      our findings suggest the existence, abundance and effectiveness of native
      turncoats in a community could greatly influence invasion success at large
      scales.

PMID- 29367391
TI  - Brain size affects performance in a reversal-learning test.
AB  - It has become increasingly clear that a larger brain can confer cognitive
      benefits. Yet not all of the numerous aspects of cognition seem to be affected by
      brain size. Recent evidence suggests that some more basic forms of cognition, for
      instance colour vision, are not influenced by brain size. We therefore
      hypothesize that a larger brain is especially beneficial for distinct and
      gradually more complex aspects of cognition. To test this hypothesis, we assessed
      the performance of brain size selected female guppies (Poecilia reticulata) in
      two distinct aspects of cognition that differ in cognitive complexity. In a
      standard reversal-learning test we first investigated basic learning ability with
      a colour discrimination test, then reversed the reward contingency to
      specifically test for cognitive flexibility. We found that large-brained females
      outperformed small-brained females in the reversed-learning part of the test but
      not in the colour discrimination part of the test. Large-brained individuals are
      hence cognitively more flexible, which probably yields fitness benefits, as they
      may adapt more quickly to social and/or ecological cognitive challenges. Our
      results also suggest that a larger brain becomes especially advantageous with
      increasing cognitive complexity. These findings corroborate the significance of
      brain size for cognitive evolution.

PMID- 29367392
TI  - Evidence that fertility trades off with early offspring fitness as males age.
AB  - Models of ageing predict that sperm function and fertility should decline with
      age as sperm are exposed to free radical damage and mutation accumulation.
      However, theory also suggests that mating with older males should be beneficial
      for females because survival to old age is a demonstration of a male's high
      genetic and/or phenotypic quality. Consequently, declines in sperm fitness may be
      offset by indirect fitness benefits exhibited in offspring. While numerous
      studies have investigated age-based declines in male fertility, none has taken
      the integrated approach of studying age-based effects on both male fertility and
      offspring fitness. Here, using a cohort-based longitudinal study of zebrafish
      (Danio rerio), we report a decline in male mating success and fertility with male
      age but also compensating indirect benefits. Using in vitro fertilization, we
      show that offspring from older males exhibit superior early survival compared to
      those from their youngest counterparts. These findings suggest that the high
      offspring fitness observed for the subset of males that survive to an old age
      (approx. 51% in this study) may represent compensating benefits for declining
      fertility with age, thus challenging widely held views about the fitness costs of
      mating with older males.

PMID- 29367394
TI  - How animals follow the stars.
AB  - Throughout history, the stars have provided humans with ever more information
      about our world, enabling increasingly accurate systems of navigation in addition
      to fuelling some of the greatest scientific controversies. What information
      animals have evolved to extract from a starry sky and how they do so, is a topic
      of study that combines the practical and theoretical challenges faced by both
      astronomers and field biologists. While a number of animal species have been
      demonstrated to use the stars as a source of directional information, the
      strategies that these animals use to convert this complex and variable pattern of
      dim-light points into a reliable 'stellar orientation' cue have been more
      difficult to ascertain. In this review, we assess the stars as a visual stimulus
      that conveys directional information, and compare the bodies of evidence
      available for the different stellar orientation strategies proposed to date. In
      this context, we also introduce new technologies that may aid in the study of
      stellar orientation, and suggest how field experiments may be used to
      characterize the mechanisms underlying stellar orientation.

PMID- 29367393
TI  - Species delimitation for the molecular taxonomy and ecology of the widely
      distributed microbial eukaryote genus Euplotes (Alveolata, Ciliophora).
AB  - Recent advances in high-throughput sequencing and metabarcoding technologies are
      revolutionizing our understanding of the diversity and ecology of microbial
      eukaryotes (protists). The interpretation of protist diversity and the
      elucidation of their ecosystem function are, however, impeded by problems with
      species delimitation, especially as it applies to molecular taxonomy. Here, using
      the ciliate Euplotes as an example, we describe approaches for species
      delimitation based on integrative taxonomy by using evolutionary and ecological
      perspectives and selecting the most appropriate metabarcoding gene markers as
      proxies for species units. Our analyses show that: Euplotes (sensu lato)
      comprises six distinct clades, mainly as result of ecological speciation; the
      validity of the genera Euplotes (sensu stricto), Euplotoides, Euplotopsis and
      Moneuplotes are not supported; the vannus-type group, which includes species
      without distinct morphological differences, seems to be undergoing incipient
      speciation and contains cryptic species; the hypervariable V4 region of the small
      subunit rDNA and D1-D2 region of the large subunit rDNA are the promising
      candidates for general species delimitation in Euplotes.

PMID- 29367395
TI  - Simple decision rules underlie collaborative hunting in yellow saddle goatfish.
AB  - Collaborative hunting, the coordination of animal behaviour in space and time to
      capture prey, is reported in several vertebrate species. However, previous
      studies are observational, hampering our ability to identify individual decision
      rules that result in collaboration. We experimentally investigated collaborative
      hunting in yellow saddle goatfish (Parupeneus cyclostomus) by exposing pairs to a
      mock prey that fled to an artificial shelter with multiple entrances. The first
      fish to initiate the chase (the 'initiator') was always closest to the prey and
      pursued it directly in its path. Conversely, the behaviour of the second goatfish
      (the 'follower') depended on its spatial position relative to the initiator. When
      the follower was less than one body length behind the initiator, it also
      accelerated directly towards the prey in over 95% of cases. However, if the two
      goatfish were separated by a distance of one body length or more, the follower
      chose a less direct route to reach the prey in 87% of cases. In this scenario,
      the follower often reached the prey's more distant refuge first, which might
      increase its hunting success or block the prey's escape path under natural
      conditions. Our findings suggest that coordinated hunting behaviour can result
      from simple, self-serving decisions.

PMID- 29367396
TI  - Trust your gut: using physiological states as a source of information is almost
      as effective as optimal Bayesian learning.
AB  - Approaches to understanding adaptive behaviour often assume that animals have
      perfect information about environmental conditions or are capable of
      sophisticated learning. If such learning abilities are costly, however, natural
      selection will favour simpler mechanisms for controlling behaviour when faced
      with uncertain conditions. Here, we show that, in a foraging context, a strategy
      based only on current energy reserves often performs almost as well as a Bayesian
      learning strategy that integrates all previous experiences to form an optimal
      estimate of environmental conditions. We find that Bayesian learning gives a
      strong advantage only if fluctuations in the food supply are very strong and
      reasonably frequent. The performance of both the Bayesian and the reserve-based
      strategy are more robust to inaccurate knowledge of the temporal pattern of
      environmental conditions than a strategy that has perfect knowledge about current
      conditions. Studies assuming Bayesian learning are often accused of being
      unrealistic; our results suggest that animals can achieve a similar level of
      performance to Bayesians using much simpler mechanisms based on their
      physiological state. More broadly, our work suggests that the ability to use
      internal states as a source of information about recent environmental conditions
      will have weakened selection for sophisticated learning and decision-making
      systems.

PMID- 29367397
TI  - Simpler grammar, larger vocabulary: How population size affects language.
AB  - Languages with many speakers tend to be structurally simple while small
      communities sometimes develop languages with great structural complexity.
      Paradoxically, the opposite pattern appears to be observed for non-structural
      properties of language such as vocabulary size. These apparently opposite
      patterns pose a challenge for theories of language change and evolution. We use
      computational simulations to show that this inverse pattern can depend on a
      single factor: ease of diffusion through the population. A population of
      interacting agents was arranged on a network, passing linguistic conventions to
      one another along network links. Agents can invent new conventions, or replicate
      conventions that they have previously generated themselves or learned from other
      agents. Linguistic conventions are either Easy or Hard to diffuse, depending on
      how many times an agent needs to encounter a convention to learn it. In large
      groups, only linguistic conventions that are easy to learn, such as words, tend
      to proliferate, whereas small groups where everyone talks to everyone else allow
      for more complex conventions, like grammatical regularities, to be maintained.
      Our simulations thus suggest that language, and possibly other aspects of
      culture, may become simpler at the structural level as our world becomes
      increasingly interconnected.

PMID- 29367398
TI  - Whole-body photoreceptor networks are independent of 'lenses' in brittle stars.
AB  - Photoreception and vision are fundamental aspects of animal sensory biology and
      ecology, but important gaps remain in our understanding of these processes in
      many species. The colour-changing brittle star Ophiocoma wendtii is iconic in
      vision research, speculatively possessing a unique whole-body visual system that
      incorporates information from nerve bundles underlying thousands of crystalline
      'microlenses'. The hypothesis that these might form a sophisticated compound eye
      like system regulated by chromatophores has been extensively reiterated, with
      investigations into biomimetic optics and similar supposedly 'visual' structures
      in living and fossil taxa. However, no photoreceptors or visual behaviours have
      ever been identified. We present the first evidence of photoreceptor networks in
      three Ophiocoma species, both with and without microlenses and colour-changing
      behaviour. High-resolution microscopy, immunohistochemistry and synchrotron
      tomography demonstrate that putative photoreceptors cover the animals' oral,
      lateral and aboral surfaces, but are absent at the hypothesized focal points of
      the microlenses. The structural optics of these crystal 'lenses' are an
      exaptation and do not fulfil any apparent visual role. This contradicts previous
      studies, yet the photoreceptor network in Ophiocoma appears even more widespread
      than previously anticipated, both taxonomically and anatomically.

PMID- 29367399
TI  - Cooperative defence operates by social modulation of biogenic amine levels in the
      honey bee brain.
AB  - The defence of a society often requires that some specialized members coordinate
      to repel a threat at personal risk. This is especially true for honey bee guards,
      which defend the hive and may sacrifice their lives upon stinging. Central to
      this cooperative defensive response is the sting alarm pheromone, which has
      isoamyl acetate (IAA) as its main component. Although this defensive behaviour
      has been well described, the neural mechanisms triggered by IAA to coordinate
      stinging have long remained unknown. Here we show that IAA upregulates brain
      levels of serotonin and dopamine, thereby increasing the likelihood of an
      individual bee to attack and sting. Pharmacological enhancement of the levels of
      both amines induces higher defensive responsiveness, while decreasing them via
      antagonists decreases stinging. Our results thus uncover the neural mechanism by
      which an alarm pheromone recruits individuals to attack and repel a threat, and
      suggest that the alarm pheromone of honey bees acts on their response threshold
      rather than as a direct trigger.

PMID- 29367400
TI  - Prevalence of disruptive selection predicts extent of species differentiation in
      Lake Victoria cichlids.
AB  - Theory suggests that speciation with gene flow is most likely when both sexual
      and ecological selection are divergent or disruptive. Divergent sexual and
      natural selection on the visual system have been demonstrated before in
      sympatric, morphologically similar sister species of Lake Victoria cichlids, but
      this does not explain the subtle morphological differences between them. To
      investigate the significance of natural selection on morphology during
      speciation, we here ask whether the prevalence of disruptive ecological selection
      differs between sympatric sister species that are at different stages of
      speciation. Some of our species pairs do (Pundamilia) and others do not
      (Neochromis) differ distinctively in sexually selected male nuptial coloration.
      We find that (i) evidence for disruptive selection, and for evolutionary response
      to it, is prevalent in traits that are differentiated between sister species;
      (ii) prevalence of both predicts the extent of genetic differentiation; and (iii)
      genetic differentiation is weaker in species pairs with conserved male nuptial
      coloration. Our results speak to the existence of two different mechanisms of
      speciation with gene flow: speciation mainly by sexual selection tightly followed
      by ecological character displacement in some cases and speciation mainly by
      divergent ecological selection in others.

PMID- 29367401
TI  - Phanerozoic pO2 and the early evolution of terrestrial animals.
AB  - Concurrent gaps in the Late Devonian/Mississippian fossil records of insects and
      tetrapods (i.e. Romer's Gap) have been attributed to physiological suppression by
      low atmospheric pO2 Here, updated stable isotope inputs inform a reconstruction
      of Phanerozoic oxygen levels that contradicts the low oxygen hypothesis (and
      contradicts the purported role of oxygen in the evolution of gigantic insects
      during the late Palaeozoic), but reconciles isotope-based calculations with other
      proxies, like charcoal. Furthermore, statistical analysis demonstrates that the
      gap between the first Devonian insect and earliest diverse insect assemblages of
      the Pennsylvanian (Bashkirian Stage) requires no special explanation if insects
      were neither diverse nor abundant prior to the evolution of wings. Rather than
      tracking physiological constraint, the fossil record may accurately record the
      transformative evolutionary impact of insect flight.

PMID- 29367402
TI  - Social brain volume is associated with in-degree social network size among older
      adults.
AB  - The social brain hypothesis proposes that large neocortex size evolved to support
      cognitively demanding social interactions. Accordingly, previous studies have
      observed that larger orbitofrontal and amygdala structures predict the size of an
      individual's social network. However, it remains uncertain how an individual's
      social connectedness reported by other people is associated with the social brain
      volume. In this study, we found that a greater in-degree network size, a measure
      of social ties identified by a subject's social connections rather than by the
      subject, significantly correlated with a larger regional volume of the
      orbitofrontal cortex, dorsomedial prefrontal cortex and lingual gyrus. By
      contrast, out-degree size, which is based on an individual's self-perceived
      connectedness, showed no associations. Meta-analytic reverse inference further
      revealed that regional volume pattern of in-degree size was specifically involved
      in social inference ability. These findings were possible because our dataset
      contained the social networks of an entire village, i.e. a global network. The
      results suggest that the in-degree aspect of social network size not only
      confirms the previously reported brain correlates of the social network but also
      shows an association in brain regions involved in the ability to infer other
      people's minds. This study provides insight into understanding how the social
      brain is uniquely associated with sociocentric measures derived from a global
      network.

PMID- 29367403
TI  - A Perfect Match Genomic Landscape Provides a Unified Framework for the Precise
      Detection of Variation in Natural and Synthetic Haploid Genomes.
AB  - We present a conceptually simple, sensitive, precise, and essentially
      nonstatistical solution for the analysis of genome variation in haploid
      organisms. The generation of a Perfect Match Genomic Landscape (PMGL), which
      computes intergenome identity with single nucleotide resolution, reveals
      signatures of variation wherever a query genome differs from a reference genome.
      Such signatures encode the precise location of different types of variants,
      including single nucleotide variants, deletions, insertions, and amplifications,
      effectively introducing the concept of a general signature of variation. The
      precise nature of variants is then resolved through the generation of targeted
      alignments between specific sets of sequence reads and known regions of the
      reference genome. Thus, the perfect match logic decouples the identification of
      the location of variants from the characterization of their nature, providing a
      unified framework for the detection of genome variation. We assessed the
      performance of the PMGL strategy via simulation experiments. We determined the
      variation profiles of natural genomes and of a synthetic chromosome, both in the
      context of haploid yeast strains. Our approach uncovered variants that have
      previously escaped detection. Moreover, our strategy is ideally suited for
      further refining high-quality reference genomes. The source codes for the
      automated PMGL pipeline have been deposited in a public repository.

PMID- 29367404
TI  - Loss of eIF4E Phosphorylation Engenders Depression-like Behaviors via Selective
      mRNA Translation.
AB  - The MAPK/ERK (mitogen-activated protein kinases/extracellular signal-regulated
      kinase) pathway is a cardinal regulator of synaptic plasticity, learning, and
      memory in the hippocampus. One of major endpoints of this signaling cascade is
      the 5' mRNA cap binding protein eIF4E (eukaryotic Initiation Factor 4E), which is
      phosphorylated on Ser 209 by MNK (MAPK-interacting protein kinases) and controls
      mRNA translation. The precise role of phospho-eIF4E in the brain is yet to be
      determined. Herein, we demonstrate that ablation of eIF4E phosphorylation in male
      mice (4Eki mice) does not impair long-term spatial or contextual fear memory, or
      the late phase of LTP. Using unbiased translational profiling in mouse brain, we
      show that phospho-eIF4E differentially regulates the translation of a subset of
      mRNAs linked to inflammation, the extracellular matrix, pituitary hormones, and
      the serotonin pathway. Consequently, 4Eki male mice display exaggerated
      inflammatory responses and reduced levels of serotonin, concomitant with
      depression and anxiety-like behaviors. Remarkably, eIF4E phosphorylation is
      required for the chronic antidepressant action of the selective serotonin
      reuptake inhibitor fluoxetine. Finally, we propose a novel phospho-eIF4E
      dependent translational control mechanism in the brain, via the GAIT complex
      (gamma IFN activated inhibitor of translation). In summary, our work proposes a
      novel translational control mechanism involved in the regulation of inflammation
      and depression, which could be exploited to design novel
      therapeutics.SIGNIFICANCE STATEMENT We demonstrate that downstream of the MAPK
      (mitogen-activated protein kinase) pathway, eukaryotic Initiation Factor 4E
      (eIF4E) Ser209 phosphorylation is not required for classical forms of hippocampal
      LTP and memory. We reveal a novel role for eIF4E phosphorylation in inflammatory
      responses and depression-like behaviors. eIF4E phosphorylation is required for
      the chronic action of antidepressants, such as fluoxetine in mice. These
      phenotypes are accompanied by selective translation of extracellular matrix,
      pituitary hormones, and serotonin pathway genes, in eIF4E phospho-mutant mice. We
      also describe a previously unidentified translational control mechanism in the
      brain, whereby eIF4E phosphorylation is required for inhibiting the translation
      of gamma IFN activated inhibitor of translation element-containing mRNAs. These
      findings can be used to design novel therapeutics for depression.

PMID- 29367405
TI  - Diversity of Internal Sensory Neuron Axon Projection Patterns Is Controlled by
      the POU-Domain Protein Pdm3 in Drosophila Larvae.
AB  - Internal sensory neurons innervate body organs and provide information about
      internal state to the CNS to maintain physiological homeostasis. Despite their
      conservation across species, the anatomy, circuitry, and development of internal
      sensory systems are still relatively poorly understood. A largely unstudied
      population of larval Drosophila sensory neurons, termed tracheal dendrite (td)
      neurons, innervate internal respiratory organs and may serve as a model for
      understanding the sensing of internal states. Here, we characterize the
      peripheral anatomy, central axon projection, and diversity of td sensory neurons.
      We provide evidence for prominent expression of specific gustatory receptor genes
      in distinct populations of td neurons, suggesting novel chemosensory functions.
      We identify two anatomically distinct classes of td neurons. The axons of one
      class project to the subesophageal zone (SEZ) in the brain, whereas the other
      terminates in the ventral nerve cord (VNC). We identify expression and a
      developmental role of the POU-homeodomain transcription factor Pdm3 in regulating
      the axon extension and terminal targeting of SEZ-projecting td neurons.
      Remarkably, ectopic Pdm3 expression is alone sufficient to switch VNC-targeting
      axons to SEZ targets, and to induce the formation of putative synapses in these
      ectopic target zones. Our data thus define distinct classes of td neurons, and
      identify a molecular factor that contributes to diversification of axon
      targeting. These results introduce a tractable model to elucidate molecular and
      circuit mechanisms underlying sensory processing of internal body status and
      physiological homeostasis.SIGNIFICANCE STATEMENT How interoceptive sensory
      circuits develop, including how sensory neurons diversify and target distinct
      central regions, is still poorly understood, despite the importance of these
      sensory systems for maintaining physiological homeostasis. Here, we characterize
      classes of Drosophila internal sensory neurons (td neurons) and uncover diverse
      axonal projections and expression of chemosensory receptor genes. We categorize
      td neurons into two classes based on dichotomous axon target regions, and
      identify the expression and role of the transcription factor Pdm3 in mediating td
      axon targeting to one of these target regions. Our results provide an entry point
      into studying internal sensory circuit development and function, and establish
      Pdm3 as a regulator of interoceptive axon targeting.

PMID- 29367406
TI  - Cortical Neural Activity Predicts Sensory Acuity Under Optogenetic Manipulation.
AB  - Excitatory and inhibitory neurons in the mammalian sensory cortex form
      interconnected circuits that control cortical stimulus selectivity and sensory
      acuity. Theoretical studies have predicted that suppression of inhibition in such
      excitatory-inhibitory networks can lead to either an increase or, paradoxically,
      a decrease in excitatory neuronal firing, with consequent effects on stimulus
      selectivity. We tested whether modulation of inhibition or excitation in the
      auditory cortex of male mice could evoke such a variety of effects in tone-evoked
      responses and in behavioral frequency discrimination acuity. We found that,
      indeed, the effects of optogenetic manipulation on stimulus selectivity and
      behavior varied in both magnitude and sign across subjects, possibly reflecting
      differences in circuitry or expression of optogenetic factors. Changes in neural
      population responses consistently predicted behavioral changes for individuals
      separately, including improvement and impairment in acuity. This correlation
      between cortical and behavioral change demonstrates that, despite the complex and
      varied effects that these manipulations can have on neuronal dynamics, the
      resulting changes in cortical activity account for accompanying changes in
      behavioral acuity.SIGNIFICANCE STATEMENT Excitatory and inhibitory interactions
      determine stimulus specificity and tuning in sensory cortex, thereby controlling
      perceptual discrimination acuity. Modeling has predicted that suppressing the
      activity of inhibitory neurons can lead to increased or, paradoxically, decreased
      excitatory activity depending on the architecture of the network. Here, we
      capitalized on differences between subjects to test whether
      suppressing/activating inhibition and excitation can in fact exhibit such
      paradoxical effects for both stimulus sensitivity and behavioral
      discriminability. Indeed, the same optogenetic manipulation in the auditory
      cortex of different mice could improve or impair frequency discrimination acuity,
      predictable from the effects on cortical responses to tones. The same
      manipulations sometimes produced opposite changes in the behavior of different
      individuals, supporting theoretical predictions for inhibition-stabilized
      networks.

PMID- 29367408
TI  - Physiology of the lung in idiopathic pulmonary fibrosis.
AB  - The clinical expression of idiopathic pulmonary fibrosis (IPF) is directly
      related to multiple alterations in lung function. These alterations derive from a
      complex disease process affecting all compartments of the lower respiratory
      system, from the conducting airways to the lung vasculature. In this article we
      review the profound alterations in lung mechanics (reduced lung compliance and
      lung volumes), pulmonary gas exchange (reduced diffusing capacity, increased dead
      space ventilation, chronic arterial hypoxaemia) and airway physiology (increased
      cough reflex and increased airway volume), as well as pulmonary haemodynamics
      related to IPF. The relative contribution of these alterations to exertional
      limitation and dyspnoea in IPF is discussed.

PMID- 29367407
TI  - An Interaction between Serotonin Receptor Signaling and Dopamine Enhances Goal
      Directed Vigor and Persistence in Mice.
AB  - The functionally selective 5-HT2C receptor ligand SB242084 can increase
      motivation and have rapid onset anti-depressant-like effects. We sought to
      identify the specific behavioral effects of SB242084 treatment and elucidate the
      mechanism in female and male mice. Using a quantitative behavioral approach, we
      determined that SB242084 increases the vigor and persistence of goal-directed
      activity across different types of physical work, particularly when work
      requirements are demanding. We found this influence of SB242084 on effort, rather
      than reward to be reflected in striatal DA measured during behavior. Using in
      vivo fast scan cyclic voltammetry, we found that SB242084 has no effect on reward
      related phasic DA release in the NAc. Using in vivo microdialysis to measure
      tonic changes in extracellular DA, we also found no changes in the NAc. In
      contrast, SB242084 treatment increases extracellular DA in the dorsomedial
      striatum, an area that plays a key role in response vigor. These findings have
      several implications. At the behavioral level, this work shows that the capacity
      to work in demanding situations can be increased, without a generalized increase
      in motor activity or reward value. At the circuit level, we identified a pathway
      restricted potentiation of DA release and showed that this was the reason for the
      increased response vigor. At the cellular level, we show that a specific
      serotonin receptor cross talks to the DA system. Together, this information
      provides promise for the development of treatments for apathy, a serious clinical
      condition that can afflict patients with psychiatric and neurological
      disorders.SIGNIFICANCE STATEMENT Motivated behaviors are modulated by reward
      value, effort demands, and cost-benefit computations. This information drives the
      decision to act, which action to select, and the intensity with which the
      selected action is performed. Because these behavioral processes are all
      regulated by DA signaling, it is very difficult to influence selected aspects of
      motivated behavior without affecting others. Here we identify a pharmacological
      treatment that increases the vigor and persistence of responding in mice, without
      increasing generalized activity or changing reactions to rewards. We show that
      the 5-HT2C-selective ligand boosts motivation by potentiating activity-dependent
      DA release in the dorsomedial striatum. These results reveal a novel strategy for
      treating patients with motivational deficits, avolition, or apathy.

PMID- 29367409
TI  - Pulmonary vascular development in congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly characterised
      by a diaphragmatic defect, persistent pulmonary hypertension (PH) and lung
      hypoplasia. The relative contribution of these three elements can vary
      considerably in individual patients. Most affected children suffer primarily from
      the associated PH, for which the therapeutic modalities are limited and
      frequently not evidence based. The vascular defects associated with PH, which is
      characterised by increased muscularisation of arterioles and capillaries, start
      to develop early in gestation. Pulmonary vascular development is integrated with
      the development of the airway epithelium. Although our knowledge is still
      incomplete, the processes involved in the growth and expansion of the vasculature
      are beginning to be unravelled. It is clear that early disturbances of this
      process lead to major pulmonary growth abnormalities, resulting in serious
      clinical challenges and in many cases death in the newborn. Here we provide an
      overview of the current molecular pathways involved in pulmonary vascular
      development. Moreover, we describe the abnormalities associated with CDH and the
      potential therapeutic approaches for this severe abnormality.

PMID- 29367410
TI  - Impact of the financial crisis on COPD burden: Greece as a case study.
AB  - Poverty and low socioeconomic status have been associated with chronic
      obstructive pulmonary disease (COPD). The current financial crisis has forced
      millions back into poverty. Greece is one of the countries hit the hardest, and
      is in the middle of a deep ongoing collapse. There have been early reports
      stating the apparent effects of the Greek downturn on respiratory health. This
      review summarises the overall impact of the financial crisis on COPD burden
      throughout the period of economic downturn by analysing the case study of Greece.
      In all levels of the healthcare system, current economic restrictions have
      reduced the capacity to prevent, diagnose and treat COPD in parallel with current
      higher detection rates of COPD. Remarkably, expenditure on healthcare has been
      reduced by >25%, resulting in major healthcare equipment shortages. Lower wages
      (by up to 20%) and higher co-payments of up to 25% of a drug's purchase price
      have led to patients struggling to afford inhaled medications. Treatment
      nonadherence has been reported, resulting in 11.5% more exacerbations and 14.1%
      more hospitalisations annually, while the mean cost per severe COPD exacerbation
      has been approximated as ?2600. Greece is a noteworthy example illustrating how
      COPD burden, quality of care and patients' outcome can be affected by economic
      crisis.

PMID- 29367411
TI  - ARDS: challenges in patient care and frontiers in research.
AB  - This review discusses the clinical challenges associated with ventilatory support
      and pharmacological interventions in patients with acute respiratory distress
      syndrome (ARDS). In addition, it discusses current scientific challenges facing
      researchers when planning and performing trials of ventilatory support or
      pharmacological interventions in these patients.Noninvasive mechanical
      ventilation is used in some patients with ARDS. When intubated and mechanically
      ventilated, ARDS patients should be ventilated with low tidal volumes. A plateau
      pressure <30 cmH2O is recommended in all patients. It is suggested that a plateau
      pressure <15 cmH2O should be considered safe. Patient with moderate and severe
      ARDS should receive higher levels of positive end-expiratory pressure (PEEP).
      Rescue therapies include prone position and neuromuscular blocking agents.
      Extracorporeal support for decapneisation and oxygenation should only be
      considered when lung-protective ventilation is no longer possible, or in cases of
      refractory hypoxaemia, respectively. Tracheotomy is only recommended when
      prolonged mechanical ventilation is expected.Of all tested pharmacological
      interventions for ARDS, only treatment with steroids is considered to have
      benefit.Proper identification of phenotypes, known to respond differently to
      specific interventions, is increasingly considered important for clinical trials
      of interventions for ARDS. Such phenotypes could be defined based on clinical
      parameters, such as the arterial oxygen tension/inspiratory oxygen fraction
      ratio, but biological marker profiles could be more promising.

PMID- 29367412
TI  - "Metabolic dysfunction in pulmonary hypertension: from basic science to clinical
      practice." Stephen Y. Chan and Lewis J. Rubin. Eur Respir Rev 2017; 26: 170094.

PMID- 29367413
TI  - High glucose contributes to the proliferation and migration of non-small cell
      lung cancer cells via GAS5-TRIB3 axis.
AB  - Despite the growing number of studies exhibited an association of diabetes
      mellitus (DM) and lung cancer progression, the concrete mechanism of DM
      aggravating lung cancer has not been elucidated. This study was to investigate
      whether and how high glucose (HG) contribute to the proliferation and migration
      of non-small cell lung cancer (NSCLC) cells in vitro. In the present study, we
      confirmed that HG promoted the proliferation and migration of NSCLC cells, and
      also induced an anti-apoptosis effect on NSCLC cells. Moreover, HG inhibited the
      expression of GAS5 in NSCLC cells but elevated the protein level of TRIB3. GAS5
      overexpression promoted the degradation of TRIB3 protein by ubiquitination and
      inhibited the HG induced-proliferation, anti-apoptosis and migration of NSCLC
      cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG
      treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly
      enhanced the proliferation, anti-apoptosis and migration in NSCLC cells through
      TRIB3, thus promoting the carcinogenesis of NSCLC.

PMID- 29367414
TI  - Plastid translation is essential for lateral root stem cell patterning in
      Arabidopsis thaliana.
AB  - The plastid evolved from a symbiotic cyanobacterial ancestor and is an essential
      organelle for plant life, but its developmental roles in roots have been largely
      overlooked. Here, we show that plastid translation is connected to the stem cell
      patterning in lateral root primordia. The RFC3 gene encodes a plastid-localized
      protein that is a conserved bacterial ribosomal protein S6 of beta/gamma
      proteobacterial origin. The rfc3 mutant developed lateral roots with disrupted
      stem cell patterning and associated with decreased leaf photosynthetic activity,
      reduced accumulation of plastid rRNAs in roots, altered root plastid gene
      expression, and changes in expression of several root stem cell regulators. These
      results suggest that deficiencies in plastid function affect lateral root stem
      cells. Treatment with the plastid translation inhibitor spectinomycin phenocopied
      the defective stem cell patterning in lateral roots and altered plastid gene
      expression observed in the rfc3 mutant. Additionally, when prps17 defective in a
      plastid ribosomal protein was treated with low concentrations of spectinomycin,
      it also phenocopied the lateral root phenotypes of rfc3 The spectinomycin
      treatment and rfc3 mutation also negatively affected symplasmic connectivity
      between primary root and lateral root primordia. This study highlights previously
      unrecognized functions of plastid translation in the stem cell patterning in
      lateral roots.

PMID- 29367415
TI  - Recombinant Human ADAMTS13 Treatment Improves Myocardial Remodeling and
      Functionality After Pressure Overload Injury in Mice.
AB  - BACKGROUND: A disintegrin-like metalloproteinase with thrombospondin motif type 1
      member 13 (ADAMTS13), the von Willebrand factor-cleaving enzyme, decreases
      leukocyte and platelet recruitment and, thus, reduces thrombosis and
      inflammation. Recombinant human ADAMTS13 (rhADAMTS13) is a novel drug candidate
      for ischemia/reperfusion injury and has shown short-term benefits in mouse models
      of myocardial injury, but long-term outcome has not been investigated. METHODS
      AND RESULTS: We evaluated the impact of rhADAMTS13 on cardiac remodeling,
      scarring, and contractile function, under chronic left ventricular pressure
      overload. The role of von Willebrand factor and the effect of rhADAMTS13
      treatment were studied. This model of heart failure, based on ascending aortic
      constriction, produces a coronary inflammatory response and microvascular
      dysfunction, resulting in fibrotic remodeling and cardiac failure. Mice were
      treated with either rhADAMTS13 or vehicle and assessed for coronary vascular
      inflammation and ventricular function at several postsurgical time points, as
      well as for cardiac fibrosis after 4 weeks. Early upon induction of pressure
      overload under rhADAMTS13 treatment, we detected less endothelial-lumen
      associated von Willebrand factor, fewer platelet aggregates, and decreased
      activated transforming growth factor-beta1 levels than in vehicle-treated mice.
      We observed significant preservation of cardiac function and decrease in fibrotic
      remodeling as a result of rhADAMTS13 administration. CONCLUSIONS: Herein, we show
      that rhADAMTS13 decreases coronary vascular dysfunction and improves cardiac
      remodeling after left ventricular pressure overload in mice. We propose that this
      effect may, at least in part, be the result of decreased von Willebrand factor
      mediated recruitment of platelets, a major source of the activated profibrotic
      cytokine transforming growth factor-beta1. Our study further supports the
      therapeutic potential of rhADAMTS13 for conditions characterized by inflammatory
      cardiac damage that results in fibrosis.

PMID- 29367416
TI  - Reduced Long-Term Risk of Aortic Aneurysm and Aortic Dissection Among Individuals
      With Type 2 Diabetes Mellitus: A Nationwide Observational Study.
AB  - BACKGROUND: No studies have examined long-term risks for aortic aneurysm (AA) and
      aortic dissection (AD) or mortality after AA or AD hospitalization among patients
      with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: In this observational
      cohort study, we linked data for patients with T2DM in the Swedish National
      Diabetes Register, and 5 individually matched population-based control subjects
      (CSs) without diabetes mellitus (on the basis of sex, age, and county), to other
      national databases to capture hospitalizations and death. We examined the risk of
      hospitalization for AA and AD, as well as mortality risk after AA and AD using
      Kaplan-Meier curves and Cox regression hazards models. Data on 448 319 patients
      with T2DM and 2 251 015 CSs were obtained between 1998 and 2015. Mean follow-up
      time was 7.0 years for the T2DM group and 7.2 years for the CS group. Patients
      with T2DM had a relative risk reduction of 28% (hazard ratio, 0.72; 95%
      confidence interval, 0.68-0.76; P<0.0001) for AA and a 47% relative risk
      reduction (hazard ratio, 0.53; 95% confidence interval, 0.42-0.65; P<0.0001) for
      AD compared with CSs. Patients with T2DM had a relative risk reduction of 12%
      (hazard ratio, 0.88; 95% confidence interval, 0.82-0.94; P<0.0001) for mortality
      after hospitalization for AA, and unaltered risk (hazard ratio, 1.07; 95%
      confidence interval, 0.85-1.34; P=0.5859) for mortality after AD, up to 2 years
      compared with CSs. CONCLUSIONS: Patients with T2DM had significantly reduced
      risks of AA and AD as well as reduced risk of mortality after hospitalization for
      AA, compared to CS. Data suggest that glycated cross-links in aortic tissue may
      play a protective role in the progression of aortic diseases among patients with
      T2DM.

PMID- 29367417
TI  - Comparative Cardiovascular Risk of Abatacept and Tumor Necrosis Factor Inhibitors
      in Patients With Rheumatoid Arthritis With and Without Diabetes Mellitus: A
      Multidatabase Cohort Study.
AB  - BACKGROUND: We examined the cardiovascular risk of abatacept compared with tumor
      necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis with and
      without diabetes mellitus (DM). METHODS AND RESULTS: We conducted a cohort study
      of patients with rheumatoid arthritis who newly started abatacept or TNF
      inhibitors using claims data from Medicare and MarketScan. The primary outcome
      was a composite cardiovascular end point of myocardial infarction (MI),
      stroke/transient ischemic attack, and coronary revascularization. To account for
      >60 baseline characteristics, abatacept initiators were 1:1 propensity score (PS)
      matched to TNF initiators in each database. Cox proportional hazards models
      estimated hazard ratio (HR) and 95% confidence interval (CI) in the PS-matched
      cohort per database. A fixed-effects meta-analysis pooled database-specific HRs.
      We included a total of 13 039 PS-matched pairs of abatacept and TNF inhibitor
      initiators (6103 pairs in Medicare and 6936 pairs in MarketScan). A total of
      34.7% in Medicare and 19.8% in MarketScan had baseline DM. The HR (95% CI) for
      the primary outcome associated with abatacept use versus TNF inhibitor was 0.81
      (0.66-0.99) in Medicare and 0.95 (0.74-1.23) in MarketScan, with a pooled HR of
      0.86 (95% CI, 0.73-1.01; P=0.3 for heterogeneity). The risk of the primary
      outcome was lower in abatacept initiators versus TNF inhibitors in the DM
      subgroup, with a pooled HR of 0.74 (95% CI, 0.57-0.96; P=0.7 for heterogeneity),
      but not in the non-DM subgroup, with a pooled HR of 0.94 (95% CI, 0.77-1.14;
      P=0.4 for heterogeneity). CONCLUSIONS: In this large population-based cohort of
      patients with rheumatoid arthritis, abatacept use appeared to be associated with
      a modestly reduced cardiovascular risk when compared with TNF inhibitor use,
      particularly in patients with DM.

PMID- 29367418
TI  - Reply to Raison and Raichlen: Why does nutrition impact social decision making?

PMID- 29367419
TI  - An evolutionary perspective on nutrition and social decision making.

PMID- 29367420
TI  - Engineered bio-inspired coating for passive flow control.
AB  - Flow separation and vortex shedding are some of the most common phenomena
      experienced by bluff bodies under relative motion with the surrounding medium.
      They often result in a recirculation bubble in regions with adverse pressure
      gradient, which typically reduces efficiency in vehicles and increases loading on
      structures. Here, the ability of an engineered coating to manipulate the large
      scale recirculation region was tested in a separated flow at moderate momentum
      thickness Reynolds number, [Formula: see text] We show that the coating, composed
      of uniformly distributed cylindrical pillars with diverging tips, successfully
      reduces the size of, and shifts downstream, the separation bubble. Despite the so
      called roughness parameter, [Formula: see text], falling within the hydrodynamic
      smooth regime, the coating is able to modulate the large-scale recirculating
      motion. Remarkably, this modulation does not induce noticeable changes in the
      near-wall turbulence levels. Supported with experimental data and theoretical
      arguments based on the averaged equations of motion, we suggest that the inherent
      mechanism responsible for the bubble modulation is essentially unsteady suction
      and blowing controlled by the increasing cross-section of the tips. The coating
      can be easily fabricated and installed and works under dry and wet conditions,
      increasing its potential impact on a diverse range of applications.

PMID- 29367421
TI  - BARD1 is necessary for ubiquitylation of nucleosomal histone H2A and for
      transcriptional regulation of estrogen metabolism genes.
AB  - Missense mutations that disrupt the RING domain of the tumor suppressor gene
      BRCA1 lead to increased risk of breast and ovarian cancer. The BRCA1 RING domain
      is a ubiquitin ligase, whose structure and function rely critically on forming a
      heterodimer with BARD1, which also harbors a RING domain. The function of the
      BARD1 RING domain is unknown. In families severely affected with breast cancer,
      we identified inherited BARD1 missense mutations Cys53Trp, Cys71Tyr, and Cys83Arg
      that alter three zinc-binding residues of the BARD1 RING domain. Each of these
      mutant BARD1 proteins retained the ability to form heterodimeric complexes with
      BRCA1 to make an active ubiquitin ligase, but the mutant BRCA1/BARD1 complexes
      were deficient in binding to nucleosomes and in ubiquitylating histone H2A. The
      BARD1 mutations also caused loss of transcriptional repression of BRCA1-regulated
      estrogen metabolism genes CYP1A1 and CYP3A4; breast epithelial cells edited to
      create heterozygous loss of BARD1 showed significantly higher expression of
      CYP1A1 and CYP3A4 Reintroduction of wild-type BARD1 into these cells restored
      CYP1A1 and CYP3A4 transcription to normal levels, but introduction of the cancer
      predisposing BARD1 RING mutants failed to do so. These results indicate that an
      intact BARD1 RING domain is critical to BRCA1/BARD1 binding to nucleosomes and
      hence to ubiquitylation of histone H2A and also critical to transcriptional
      repression of BRCA1-regulated genes active in estrogen metabolism.

PMID- 29367422
TI  - Extracellular vesicle budding is inhibited by redundant regulators of TAT-5
      flippase localization and phospholipid asymmetry.
AB  - Cells release extracellular vesicles (EVs) that mediate intercellular
      communication and repair damaged membranes. Despite the pleiotropic functions of
      EVs in vitro, their in vivo function is debated, largely because it is unclear
      how to induce or inhibit their formation. In particular, the mechanisms of EV
      release by plasma membrane budding or ectocytosis are poorly understood. We
      previously showed that TAT-5 phospholipid flippase activity maintains the
      asymmetric localization of the lipid phosphatidylethanolamine (PE) in the plasma
      membrane and inhibits EV budding by ectocytosis in Caenorhabditis elegans
      However, no proteins that inhibit ectocytosis upstream of TAT-5 were known. Here,
      we identify TAT-5 regulators associated with retrograde endosomal recycling:
      PI3Kinase VPS-34, Beclin1 homolog BEC-1, DnaJ protein RME-8, and the
      uncharacterized Dopey homolog PAD-1. PI3Kinase, RME-8, and semiredundant sorting
      nexins are required for the plasma membrane localization of TAT-5, which is
      important to maintain PE asymmetry and inhibit EV release. PAD-1 does not
      directly regulate TAT-5 localization, but is required for the lipid flipping
      activity of TAT-5. PAD-1 also has roles in endosomal trafficking with the GEF
      like protein MON-2, which regulates PE asymmetry and EV release redundantly with
      sorting nexins independent of the core retromer. Thus, in addition to uncovering
      redundant intracellular trafficking pathways, our study identifies additional
      proteins that regulate EV release. This work pinpoints TAT-5 and PE as key
      regulators of plasma membrane budding, further supporting the model that PE
      externalization drives ectocytosis.

PMID- 29367424
TI  - Pharmacokinetics, safety, and patient acceptability of subcutaneous versus
      intramuscular testosterone injection for gender-affirming therapy: A pilot study.
AB  - PURPOSE: Results of a study comparing testosterone exposure and tolerability with
      subcutaneous versus i.m. administration are presented. METHODS: In a prospective,
      open-label, crossover study, adult participants already on stable i.m.
      testosterone gender-affirming therapy self-injected testosterone cypionate or
      enanthate i.m. for 3 weeks followed by subcutaneous injections for 8 weeks.
      Trough serum testosterone concentrations were determined weekly, and serial total
      serum testosterone (TST) concentrations were determined on postinjection days 1,
      3, and 5 of weeks 3 and 11. Hemoglobin and alanine transaminase (ALT) levels were
      measured at week 3 (the first visit), with repeat measurements at week 11 (the
      final visit). The dose-normalized area under the time-concentration curve (AUC)
      was calculated during weeks 3 and 11. RESULTS: Fourteen transgender males (mean
      age, 30 +/- 10 years) participated in the study. The mean hemoglobin values at
      the first and final visits were 160 +/- 9 and 153 +/- 9 g/L, respectively (p >
      0.05); the mean ALT values were 18 +/- 6 and 21 +/- 10 IU/L (p > 0.05). Total
      testosterone exposure was comparable with subcutaneous versus i.m. injection
      (mean AUC, 1.7 +/- 0.6 nmol.days/L/mg versus 1.9 +/- 0.6 nmol.days/L/mg; p >
      0.05). Information collected via weekly questionnaires indicated that the
      subcutaneous route was more tolerable, with lower self-reported scores for
      preinjection anxiety, pain during injection, and postinjection pain. CONCLUSION:
      The subcutaneous route for the injection of testosterone was well tolerated and
      appeared to be as effective as i.m. injection in delivering equivalent TST
      levels, although there was wide intrapatient and interpatient variability.

PMID- 29367423
TI  - Chemotherapy induces enrichment of CD47+/CD73+/PDL1+ immune evasive triple
      negative breast cancer cells.
AB  - Triple-negative breast cancer (TNBC) is treated with cytotoxic chemotherapy and
      is often characterized by early relapse and metastasis. To form a secondary
      (recurrent and/or metastatic) tumor, a breast cancer cell must evade the innate
      and adaptive immune systems. CD47 enables cancer cells to evade killing by
      macrophages, whereas CD73 and PDL1 mediate independent mechanisms of evasion of
      cytotoxic T lymphocytes. Here, we report that treatment of human or murine TNBC
      cells with carboplatin, doxorubicin, gemcitabine, or paclitaxel induces the
      coordinate transcriptional induction of CD47, CD73, and PDL1 mRNA and protein
      expression, leading to a marked increase in the percentage of CD47+CD73+PDL1+
      breast cancer cells. Genetic or pharmacological inhibition of hypoxia-inducible
      factors (HIFs) blocked chemotherapy-induced enrichment of CD47+CD73+PDL1+ TNBC
      cells, which were also enriched in the absence of chemotherapy by incubation
      under hypoxic conditions, leading to T cell anergy or death. Treatment of mice
      with cytotoxic chemotherapy markedly increased the intratumoral ratio of
      regulatory/effector T cells, an effect that was abrogated by HIF inhibition. Our
      results delineate an HIF-dependent transcriptional mechanism contributing to TNBC
      progression and suggest that combining chemotherapy with an HIF inhibitor may
      prevent countertherapeutic induction of proteins that mediate evasion of innate
      and adaptive antitumor immunity.

PMID- 29367425
TI  - D-Dimer Predicts Long-Term Cause-Specific Mortality, Cardiovascular Events, and
      Cancer in Patients With Stable Coronary Heart Disease.
AB  - BACKGROUND: D-dimer, a degradation product of cross-linked fibrin, is a marker
      for hypercoagulability and thrombotic events. Moderately elevated levels of D
      dimer are associated with the risk of venous and arterial events in patients with
      vascular disease. We assessed the role of D-dimer levels in predicting long-term
      vascular outcomes, cause-specific mortality, and new cancers in the LIPID trial
      (Long-Term Intervention with Pravastatin in Ischaemic Disease) in the context of
      other risk factors. METHODS: LIPID randomized patients to placebo or pravastatin
      40 mg/d 5 to 38 months after myocardial infarction or unstable angina. D-dimer
      levels were measured at baseline and at 1 year. Median follow-up was 6.0 years
      during the trial and 16 years in total. RESULTS: Baseline D-dimer levels for 7863
      patients were grouped by quartile (<=112, 112-173, 173-273, >273 ng/mL). Higher
      levels were associated with older age, female sex, history of hypertension, poor
      renal function, and elevated levels of B-natriuretic peptide, high-sensitivity C
      reactive protein, and sensitive troponin I (each P<0.001). During the first 6
      years, after adjustment for up to 30 additional risk factors, higher D-dimer was
      associated with a significantly increased risk of a major coronary event
      (quartile 4 versus 1: hazard ratio [HR], 1.45; 95% confidence interval, 1.21
      1.74), major cardiovascular disease (CVD) event (HR, 1.45; 95% confidence
      interval, 1.23-1.71) and venous thromboembolism (HR, 4.03; 95% confidence
      interval, 2.31-7.03; each P<0.001). During the 16 years overall, higher D-dimer
      was an independent predictor of all-cause mortality (HR, 1.59), CVD mortality
      (HR, 1.61), cancer mortality (HR, 1.54), and non-CVD noncancer mortality (HR,
      1.57; each P<0.001), remaining significant for deaths resulting from each cause
      occurring beyond 10 years of follow-up (each P<=0.01). Higher D-dimer also
      independently predicted an increase in cancer incidence (HR, 1.16; P=0.02).The D
      dimer level increased the net reclassification index for all-cause mortality by
      4.0 and venous thromboembolism by 13.6. CONCLUSIONS: D-dimer levels predict long
      term risk of arterial and venous events, CVD mortality, and non-CVD noncancer
      mortality independent of other risk factors. D-dimer is also a significant
      predictor of cancer incidence and mortality. These results support an association
      of D-dimer with fatal events across multiple diseases and demonstrate that this
      link extends beyond 10 years' follow-up.

PMID- 29367426
TI  - Leptin Replacement Reestablishes Brain Insulin Action in the Hypothalamus in
      Congenital Leptin Deficiency.
AB  - OBJECTIVE: Human obesity is associated with impaired central insulin signaling,
      and in very rare cases, severe obesity can be caused by congenital leptin
      deficiency. In such patients, leptin replacement results in substantial weight
      loss and improvement in peripheral metabolism. RESEARCH DESIGN AND METHODS: In a
      leptin-deficient patient, we investigated the impact of leptin substitution on
      central insulin action, as quantified by changes in neuronal activity after
      intranasal insulin application. This was assessed before and during the first
      year of metreleptin substitution. RESULTS: After only 1 year, treatment with
      metreleptin reestablishes brain insulin sensitivity, particularly in the
      hypothalamus and, to a lesser degree, in the prefrontal cortex. Results are
      depicted in comparison with a control group. In our patient, brain activation
      changes were accompanied by substantial weight loss, reduced visceral adipose
      tissue, reduced intrahepatic lipid content, and improved whole-body insulin
      sensitivity. CONCLUSIONS: Leptin replacement and weight loss improved homeostatic
      insulin action in the patient in question.

PMID- 29367428
TI  - Kruppel-like Factor 4 Suppresses Serine/Threonine Kinase 33 Activation and
      Metastasis of Gastric Cancer through Reversing Epithelial-Mesenchymal Transition.
AB  - Background: Cancers with aberrant expression of Serine/threonine kinase 33
      (STK33) has been reported to be particularly aggressive. However, its expression,
      clinical significance, and biological functions in gastric cancer remain largely
      unknown. In the present study, we determined the expression and function of STK33
      in gastric cancer and delineated the clinical significance of the Kruppel-like
      factor 4 (KLF4)/STK33 signaling pathway.Methods: STK33 expression and its
      association with multiple clinicopathologic characteristics were analyzed
      immunohistochemically in human gastric cancer specimens. STK33 knockdown and
      overexpression were used to dissect the underlying mechanism of its functions in
      gastric cancer cells. Regulation and underlying mechanisms of STK33 expression by
      KLF4 in gastric cancer cells were studied using cell and molecular biological
      methods.Results: Drastically higher expression of STK33 was observed in gastric
      cancer and gastric intraepithelial neoplasia tissues compared with adjacent
      normal gastric tissues. Increased STK33 expression correlated directly with tumor
      size, lymph node, and distant metastasis; and patients with low STK33 expression
      gastric cancer were predicted to have a favorable prognosis. Enforced expression
      of STK33 promoted gastric cancer cell proliferation, migration, and invasion in
      vitro and in vivo, whereas reduced STK33 did the opposite. Moreover, STK33
      promoted epithelial-mesenchymal transition (EMT) in vitro Mechanistically, KLF4
      transcriptionally inhibited STK33 expression in gastric cancer cells. KLF4
      mediated inhibition of gastric cancer cell invasion was reversed by upregulation
      of STK33 expression.Conclusions: STK33 has pro-tumor function and is a critical
      downstream mediator of KLF4 in gastric cancer. STK33 may serve as a potential
      prognostic marker and therapeutic target for gastric cancer. Clin Cancer Res;
      24(10); 2440-51. (c)2018 AACR.

PMID- 29367427
TI  - High Baseline Levels of Tumor Necrosis Factor Receptor 1 Are Associated With
      Progression of Kidney Disease in Indigenous Australians With Diabetes: The eGFR
      Follow-up Study.
AB  - OBJECTIVE: To examine the association between soluble tumor necrosis factor
      receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous
      Australians at high risk of kidney disease. RESEARCH DESIGN AND METHODS: This
      longitudinal observational study examined participants aged >=18 years recruited
      from >20 sites across diabetes and/or kidney function strata. Baseline measures
      included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR),
      HbA1c, C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and
      medical history. Linear regression was used to estimate annual change in
      estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox
      proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for
      developing a combined renal outcome (first of a >=30% decline in eGFR with a
      follow-up eGFR <60 mL/min/1.73 m2, progression to renal replacement therapy, or
      renal death) for increasing sTNFR1. RESULTS: Over a median of 3 years,
      participants with diabetes (n = 194) in the highest compared with the lowest
      quartile of sTNFR1 experienced significantly greater eGFR decline (-4.22
      mL/min/1.73 m2/year [95% CI -7.06 to -1.38]; P = 0.004), independent of baseline
      age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes
      per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1-12.8;
      P = 0.03). No association between sTNFR1 and either renal outcome was observed
      for those without diabetes (n = 259). CONCLUSIONS: sTNFR1 is associated with
      greater kidney disease progression independent of albuminuria and eGFR in
      Indigenous Australians with diabetes. Further research is required to assess
      whether TNFR1 operates independently of other metabolic factors associated with
      kidney disease progression.

PMID- 29367429
TI  - Flt-3L Expansion of Recipient CD8alpha+ Dendritic Cells Deletes Alloreactive
      Donor T Cells and Represents an Alternative to Posttransplant Cyclophosphamide
      for the Prevention of GVHD.
AB  - Purpose: Allogeneic bone marrow transplantation (BMT) provides curative therapy
      for leukemia via immunologic graft-versus-leukemia (GVL) effects. In practice,
      this must be balanced against life threatening pathology induced by graft-versus
      host disease (GVHD). Recipient dendritic cells (DC) are thought to be important
      in the induction of GVL and GVHD.Experimental Design: We have utilized
      preclinical models of allogeneic BMT to dissect the role and modulation of
      recipient DCs in controlling donor T-cell-mediated GVHD and GVL.Results: We
      demonstrate that recipient CD8alpha+ DCs promote activation-induced clonal
      deletion of allospecific donor T cells after BMT. We compared pretransplant fms
      like tyrosine kinase-3 ligand (Flt-3L) treatment to the current clinical strategy
      of posttransplant cyclophosphamide (PT-Cy) therapy. Our results demonstrate
      superior protection from GVHD with the immunomodulatory Flt-3L approach, and
      similar attenuation of GVL responses with both strategies. Strikingly, Flt-3L
      treatment permitted maintenance of the donor polyclonal T-cell pool, where PT-Cy
      did not.Conclusions: These data highlight pre-transplant Flt-3L therapy as a
      potent new therapeutic strategy to delete alloreactive T cells and prevent GVHD,
      which appears particularly well suited to haploidentical BMT where the control of
      infection and the prevention of GVHD are paramount. Clin Cancer Res; 24(7); 1604
      16. (c)2018 AACR.

PMID- 29367430
TI  - Molecular Markers Increase Precision of the European Association of Urology Non
      Muscle-Invasive Bladder Cancer Progression Risk Groups.
AB  - Purpose: The European Association of Urology (EAU) guidelines for non-muscle
      invasive bladder cancer (NMIBC) recommend risk stratification based on
      clinicopathologic parameters. Our aim was to investigate the added value of
      biomarkers to improve risk stratification of NMIBC.Experimental Design: We
      prospectively included 1,239 patients in follow-up for NMIBC in six European
      countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and
      ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression
      analyses identified markers that were significantly associated with progression
      to muscle-invasive disease. The progression incidence rate (PIR = rate of
      progression per 100 patient-years) was calculated for subgroups.Results: In our
      cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor
      progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%)
      progressed to muscle-invasive disease. The limited number of progressors in this
      large cohort compared with older studies is likely due to improved treatment in
      the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3
      were significantly associated with progression (HR = 0.34, 2.53, and 2.64,
      respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3
      mutation status and methylation of GATA2, this cohort could be reclassified into
      a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32,
      49.7%), and a poor class (PIR = 7.66, 24.0%).Conclusions: We conclude that the
      addition of selected biomarkers to the EAU risk stratification increases its
      accuracy and identifies a subset of NMIBC patients with a very high risk of
      progression. Clin Cancer Res; 24(7); 1586-93. (c)2018 AACR.

PMID- 29367431
TI  - Evaluating Mismatch Repair Deficiency in Pancreatic Adenocarcinoma: Challenges
      and Recommendations.
AB  - Purpose: Immune checkpoint inhibition has been shown to generate profound and
      durable responses in mismatch repair deficient (MMR-D) solid tumors and has
      elicited interest in detection tools and strategies to guide therapeutic decision
      making. Herein we address questions on the appropriate screening, detection
      methods, patient selection, and initiation of therapy for MMR-D pancreatic ductal
      adenocarcinoma (PDAC) and assess the utility of next-generation sequencing (NGS)
      in providing additional prognostic and predictive information for MMR-D
      PDAC.Experimental Design: Archival and prospectively acquired samples and matched
      normal DNA from N = 833 PDAC cases were analyzed using a hybridization capture
      based, NGS assay designed to perform targeted deep sequencing of all exons and
      selected introns of 341 to 468 cancer-associated genes. A computational program
      using NGS data derived the MSI status from the tumor-normal paired genome
      sequencing data. Available germline testing, IHC, and microsatellite instability
      (MSI) PCR results were reviewed to assess and confirm MMR-D and MSI
      status.Results: MMR-D in PDAC is a rare event among PDAC patients (7/833),
      occurring at a frequency of 0.8%. Loss of MMR protein expression by IHC, high
      mutational load, and elevated MSIsensor scores were correlated with MMR-D PDAC.
      All 7 MMR-D PDAC patients in the study were found to have Lynch syndrome. Four
      (57%) of the MMR-D patients treated with immune checkpoint blockade had treatment
      benefit (1 complete response, 2 partial responses, 1 stable disease).Conclusions:
      An integrated approach of germline testing and somatic analyses of tumor tissues
      in advanced PDAC using NGS may help guide future development of immune and
      molecularly directed therapies in PDAC patients. Clin Cancer Res; 24(6); 1326-36.
      (c)2018 AACR.

PMID- 29367432
TI  - Within country inequalities in caesarean section rates: observational study of 72
      low and middle income countries.
AB  - OBJECTIVE: To provide an update on economic related inequalities in caesarean
      section rates within countries. DESIGN: Secondary analysis of demographic and
      health surveys and multiple indicator cluster surveys. SETTING: 72 low and middle
      income countries with a survey conducted between 2010 and 2014 for analysis of
      the latest situation of inequality, and 28 countries with a survey also conducted
      between 2000 and 2004 for analysis of the change in inequality over time.
      PARTICIPANTS: Women aged 15-49 years with a live birth during the two or three
      years preceding the survey. MAIN OUTCOME MEASURES: Data on caesarean section were
      disaggregated by asset based household wealth status and presented separately for
      five subgroups, ranging from the poorest to the richest fifth. Absolute and
      relative inequalities were measured using difference and ratio measures. The pace
      of change in the poorest and richest fifths was compared using a measure of
      excess change. RESULTS: National caesarean section rates ranged from 0.6% in
      South Sudan to 58.9% in the Dominican Republic. Within countries, caesarean
      section rates were lowest in the poorest fifth (median 3.7%) and highest in the
      richest fifth (median 18.4%). 18 out of 72 study countries reported a difference
      of 20 percentage points or higher between the richest and poorest fifth. The
      highest caesarean section rates and greatest levels of absolute inequality were
      observed in countries from the region of the Americas, whereas countries from the
      African region had low levels of caesarean use and comparatively lower levels of
      absolute inequality, although relative inequality was quite high in some
      countries. 26 out of 28 countries reported increases in caesarean section rates
      over time. Rates tended to increase faster in the richest fifth (median 0.9
      percentage points per year) compared with the poorest fifth (median 0.2
      percentage points per year), indicating an increase in inequality over time in
      most of these countries. CONCLUSIONS: Substantial within country economic
      inequalities in caesarean deliveries remain. These inequalities might be due to a
      combination of inadequate access to emergency obstetric care among the poorest
      subgroups and high levels of caesarean use without medical indication in the
      richest subgroups, especially in middle income countries. Country specific
      strategies should address these inequalities to improve maternal and newborn
      health.

PMID- 29367433
TI  - N-glycome of the Lysosomal Glycocalyx is Altered in Niemann-Pick Type C Disease
      (NPC) Model Cells.
AB  - Increasing evidence implicates lysosomal dysfunction in the pathogenesis of
      neurodegenerative diseases, including the rare inherited lysosomal storage
      disorders (LSDs) and the most common neurodegenerative diseases, such as
      Alzheimer's and Parkinson's disease (AD and PD). Although the triggers of the
      lysosomal impairment may involve the accumulated macromolecules or dysfunction of
      the lysosomal enzymes, the role of the lysosomal glycocalyx in the lysosomal
      (dys)function has not been studied. The goal of this work was to analyze whether
      there are changes in the lysosomal glycocalyx in a cellular model of a LSD
      Niemann-Pick type C disease (NPC). Using the ferrofluid nanoparticles we isolated
      lysosomal organelles from NPC1-null and CHOwt cells. The magnetically isolated
      lysosomal fractions were enriched with the lysosomal marker protein LAMP1 and
      showed the key features of NPC disease: 3-fold higher cholesterol content and 4-5
      fold enlarged size of the particles compared with the lysosomal fractions of wt
      cells. These lysosomal fractions were further processed to isolate lysosomal
      membrane proteins using Triton X-114 and their N-glycome was analyzed by HILIC
      UPLC. N-glycans presented in each chromatographic peak were elucidated using
      MALDI-TOF/TOF-MS. We detected changes in the N-glycosylation pattern of the
      lysosomal glycocalyx of NPC1-null versus wt cells which involved high-mannose and
      sialylated N-glycans. To the best of our knowledge this study is the first to
      report N-glycome profiling of the lysosomal glycocalyx in NPC disease cellular
      model and the first to report the specific changes in the lysosomal glycocalyx in
      NPC1-null cells. We speculate that changes in the lysosomal glycocalyx may
      contribute to lysosomal (dys)function. Further glycome profiling of the lysosomal
      glycocalyx in other LSDs as well as the most common neurodegenerative diseases,
      such as AD and PD, is necessary to better understand the role of the lysosomal
      glycocalyx and to reveal its potential contribution in lysosomal dysfunction
      leading to neurodegeneration.

PMID- 29367434
TI  - Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative
      Therapeutic Targets and a Subtype-independent Signature of Spliceosome
      Dysregulation.
AB  - Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell cancer exhibiting a
      wide spectrum of disease courses and treatment responses. Molecular
      characterization of RNA and DNA from CLL cases has led to the identification of
      important driver mutations and disease subtypes, but the precise mechanisms of
      disease progression remain elusive. To further our understanding of CLL biology
      we performed isobaric labeling and mass spectrometry proteomics on 14 CLL
      samples, comparing them with B-cells from healthy donors (HDB). Of 8694
      identified proteins, ~6000 were relatively quantitated between all samples
      (q<0.01). A clear CLL signature, independent of subtype, of 544 significantly
      overexpressed proteins relative to HDB was identified, highlighting established
      hallmarks of CLL (e.g. CD5, BCL2, ROR1 and CD23 overexpression). Previously
      unrecognized surface markers demonstrated overexpression (e.g. CKAP4, PIGR, TMCC3
      and CD75) and three of these (LAX1, CLEC17A and ATP2B4) were implicated in B-cell
      receptor signaling, which plays an important role in CLL pathogenesis. Several
      other proteins (e.g. Wee1, HMOX1/2, HDAC7 and INPP5F) were identified with
      significant overexpression that also represent potential targets. Western
      blotting confirmed overexpression of a selection of these proteins in an
      independent cohort. mRNA processing machinery were broadly upregulated across the
      CLL samples. Spliceosome components demonstrated consistent overexpression (p =
      1.3 * 10-21) suggesting dysregulation in CLL, independent of SF3B1 mutations.
      This study highlights the potential of proteomics in the identification of
      putative CLL therapeutic targets and reveals a subtype-independent protein
      expression signature in CLL.

PMID- 29367436
TI  - Differential equation methods for simulation of GFP kinetics in non-steady state
      experiments.
AB  - Genetically encoded fluorescent proteins, combined with fluorescence microscopy,
      are widely used in cell biology to collect kinetic data on intracellular
      trafficking. Methods for extraction of quantitative information from these data
      are based on the mathematics of diffusion and tracer kinetics. Current methods,
      although useful and powerful, depend on the assumption that the cellular system
      being studied is in a steady state, that is, the assumption that all the
      molecular concentrations and fluxes are constant for the duration of the
      experiment. Here, we derive new tracer kinetic analytical methods for non-steady
      state biological systems by constructing mechanistic nonlinear differential
      equation models of the underlying cell biological processes and linking them to a
      separate set of differential equations governing the kinetics of the fluorescent
      tracer. Linking the two sets of equations is based on a new application of the
      fundamental tracer principle of indistinguishability and, unlike current methods,
      supports correct dependence of tracer kinetics on cellular dynamics. This
      approach thus provides a general mathematical framework for applications of GFP
      fluorescence microscopy (including photobleaching [FRAP, FLIP] and
      photoactivation to frequently encountered experimental protocols involving
      physiological or pharmacological perturbations (e.g., growth factors,
      neurotransmitters, acute knockouts, inhibitors, hormones, cytokines, and
      metabolites) that initiate mechanistically informative intracellular transients.
      When a new steady state is achieved, these methods automatically reduce to
      classical steady state tracer kinetic analysis.

PMID- 29367435
TI  - Interaction between the Caenorhabditis elegans centriolar protein SAS-5 and
      microtubules facilitates organelle assembly.
AB  - Centrioles are microtubule-based organelles that organize the microtubule network
      and seed the formation of cilia and flagella. New centrioles assemble through a
      stepwise process dependent notably on the centriolar protein SAS-5 in
      Caenorhabditis elegans SAS-5 and its functional homologues in other species form
      oligomers that bind the centriolar proteins SAS-6 and SAS-4, thereby forming an
      evolutionarily conserved structural core at the onset of organelle assembly.
      Here, we report a novel interaction of SAS-5 with microtubules. Microtubule
      binding requires SAS-5 oligomerization and a disordered protein segment that
      overlaps with the SAS-4 binding site. Combined in vitro and in vivo analysis of
      select mutants reveals that the SAS-5-microtubule interaction facilitates
      centriole assembly in C. elegans embryos. Our findings lead us to propose that
      the interdependence of SAS-5 oligomerization and microtubule binding reflects an
      avidity mechanism, which also strengthens SAS-5 associations with other centriole
      components and, thus, promotes organelle assembly.

PMID- 29367437
TI  - Comment: Genotype-phenotype correlations in NF1: A case for routine genetic
      testing.

PMID- 29367438
TI  - Intravenous thrombolysis and platelet count.
AB  - OBJECTIVE: To study the effect of platelet count (PC) on bleeding risk and
      outcome in stroke patients treated with IV thrombolysis (IVT) and to explore
      whether withholding IVT in PC < 100 * 109/L is supported. METHODS: In this
      prospective multicenter, IVT register-based study, we compared PC with
      symptomatic intracranial hemorrhage (sICH; Second European-Australasian Acute
      Stroke Study [ECASS II] criteria), poor outcome (modified Rankin Scale score 3
      6), and mortality at 3 months. PC was used as a continuous and categorical
      variable distinguishing thrombocytopenia (<150 * 109/L), thrombocytosis (>450 *
      109/L), and normal PC (150-450 * 109/L [reference group]). Moreover, PC < 100 *
      109/L was compared to PC >= 100 * 109/L. Unadjusted and adjusted odds ratios
      (ORs) with 95% confidence intervals (CIs) from the logistic regression models
      were calculated. RESULTS: Among 7,533 IVT-treated stroke patients, 6,830 (90.7%)
      had normal PC, 595 (7.9%) had thrombocytopenia, and 108 (1.4%) had
      thrombocytosis. Decreasing PC (every 10 * 109/L) was associated with increasing
      risk of sICH (ORadjusted 1.03, 95% CI 1.02-1.05) but decreasing risk of poor
      outcome (ORadjusted 0.99, 95% CI 0.98-0.99) and mortality (ORadjusted 0.98, 95%
      CI 0.98-0.99). The risk of sICH was higher in patients with thrombocytopenic than
      in patients with normal PC (ORadjusted 1.73, 95% CI 1.24-2.43). However, the risk
      of poor outcome (ORadjusted 0.89, 95% CI 0.39-1.97) and mortality (ORadjusted
      1.09, 95% CI 0.83-1.44) did not differ significantly. Thrombocytosis was
      associated with mortality (ORadjusted 2.02, 95% CI 1.21-3.37). Forty-four (0.3%)
      patients had PC < 100 * 109/L. Their risks of sICH (ORunadjusted 1.56, 95% CI
      0.48-5.07), poor outcome (ORadjusted 1.63, 95% CI 0.82-3.24), and mortality
      (ORadjusted 1.38, 95% CI 0.64-2.98) did not differ significantly from those of
      patients with PC >= 100 * 109/L. CONCLUSION: Lower PC was associated with
      increased risk of sICH, while higher PC indicated increased mortality. Our data
      suggest that PC modifies outcome and complications in individual patients, while
      withholding IVT in all patients with PC < 100 * 109/L is challenged.

PMID- 29367439
TI  - Randomized, double-blind, placebo-controlled trial of arimoclomol in rapidly
      progressive SOD1 ALS.
AB  - OBJECTIVE: To examine the safety and tolerability as well as the preliminary
      efficacy of arimoclomol, a heat shock protein co-inducer that promotes nascent
      protein folding, in patients with rapidly progressive SOD1 amyotrophic lateral
      sclerosis (ALS). METHODS: This was a double-blind, placebo-controlled trial in
      which patients with rapidly progressive SOD1-mutant ALS were randomized 1:1 to
      receive arimoclomol 200 mg tid or matching placebo for up to 12 months. Study
      procedures were performed using a mix of in-person and remote assessments.
      Primary outcome was safety and tolerability. Secondary outcome was efficacy, with
      survival as the principal measure. Additional efficacy measures were the rates of
      decline of the Revised ALS Functional Rating Scale (ALSFRS-R) and percent
      predicted forced expiratory volume in 6 seconds (FEV6), and the Combined
      Assessment of Function and Survival (CAFS). RESULTS: Thirty-eight participants
      were randomized. Thirty-six (19 placebo, 17 arimoclomol) were included in the
      prespecified intent-to-treat analysis. Apart from respiratory function, groups
      were generally well-balanced at baseline. Adverse events occurred infrequently,
      and were usually mild and deemed unlikely or not related to study drug. Adjusting
      for riluzole and baseline ALSFRS-R, survival favored arimoclomol with a hazard
      ratio of 0.77 (95% confidence interval [CI] 0.32-1.80). ALSFRS-R and FEV6
      declined more slowly in the arimoclomol group, with treatment differences of 0.5
      point/month (95% CI -0.63 to 1.63) and 1.24 percent predicted/month (95% CI -2.77
      to 5.25), respectively, and the CAFS similarly favored arimoclomol. CONCLUSIONS:
      This study provides Class II evidence that arimoclomol is safe and well-tolerated
      at a dosage of 200 mg tid for up to 12 months. Although not powered for
      therapeutic effect, the consistency of results across the range of prespecified
      efficacy outcome measures suggests a possible therapeutic benefit of arimoclomol.
      CLINICALTRIALSGOV IDENTIFIER: NCT00706147. CLASSIFICATION OF EVIDENCE: This study
      provides Class II evidence that arimoclomol is safe and well-tolerated at a
      dosage of 200 mg tid for up to 12 months. The study lacked the precision to
      conclude, or to exclude, an important therapeutic benefit of arimoclomol.

PMID- 29367440
TI  - Posthemorrhagic perils of prematurity.

PMID- 29367442
TI  - Searching for the good and bad high-frequency oscillations.

PMID- 29367441
TI  - Spatial variation in high-frequency oscillation rates and amplitudes in
      intracranial EEG.
AB  - OBJECTIVE: To assess the variation in baseline and seizure onset zone interictal
      high-frequency oscillation (HFO) rates and amplitudes across different anatomic
      brain regions in a large cohort of patients. METHODS: Seventy patients who had
      wide-bandwidth (5 kHz) intracranial EEG (iEEG) recordings during surgical
      evaluation for drug-resistant epilepsy between 2005 and 2014 who had high
      resolution MRI and CT imaging were identified. Discrete HFOs were identified in 2
      hour segments of high-quality interictal iEEG data with an automated detector.
      Electrode locations were determined by coregistering the patient's preoperative
      MRI with an X-ray CT scan acquired immediately after electrode implantation and
      correcting electrode locations for postimplant brain shift. The anatomic
      locations of electrodes were determined using the Desikan-Killiany brain atlas
      via FreeSurfer. HFO rates and mean amplitudes were measured in seizure onset zone
      (SOZ) and non-SOZ electrodes, as determined by the clinical iEEG seizure
      recordings. To promote reproducible research, imaging and iEEG data are made
      freely available (msel.mayo.edu). RESULTS: Baseline (non-SOZ) HFO rates and
      amplitudes vary significantly in different brain structures, and between
      homologous structures in left and right hemispheres. While HFO rates and
      amplitudes were significantly higher in SOZ than non-SOZ electrodes when analyzed
      regardless of contact location, SOZ and non-SOZ HFO rates and amplitudes were not
      separable in some lobes and structures (e.g., frontal and temporal neocortex).
      CONCLUSIONS: The anatomic variation in SOZ and non-SOZ HFO rates and amplitudes
      suggests the need to assess interictal HFO activity relative to anatomically
      accurate normative standards when using HFOs for presurgical planning.

PMID- 29367443
TI  - Outcomes among patients with direct enteral vs nasogastric tube placement after
      acute stroke.
AB  - OBJECTIVE: To compare complications, disability, and long-term mortality of
      patients who received direct enteral tube vs nasogastric tube feeding alone after
      acute stroke. METHODS: We used the Ontario Stroke Registry to identify patients
      who received direct enteral tubes (DET; gastrostomy or jejunostomy) or temporary
      nasogastric tubes (NGT) alone during hospital stay after acute ischemic stroke or
      intracerebral hemorrhage from July 1, 2003, to March 31, 2013. We used propensity
      matching to compare groups from discharge and evaluated discharge disability,
      institutionalization, complications, and mortality, with follow-up over 2 years,
      and with cumulative incidence functions used to account for competing risks.
      RESULTS: Among 1,448 patients with DET placement who survived until discharge,
      1,421 were successfully matched to patients with NGT alone. Patients with DET had
      reduced risk of death within 30 days after discharge (9.7% vs 15.3%; hazard ratio
      [HR] 0.61, 95% confidence interval [CI] 0.49-0.75), but this difference was
      eliminated after matching on length of stay and discharge disability (HR 0.90,
      95% CI 0.70-1.17). Patients with DET had higher rates of severe disability at
      discharge (modified Rankin Scale score 4-5; 89.6% vs 78.4%), discharge to long
      term care (38.0% vs 16.1%), aspiration pneumonia (14.4% vs 5.1%) and other
      complications, and mortality at 2 years (41.1% vs 35.9%). CONCLUSIONS: Patients
      with DET placement after acute stroke have more severe disability at discharge
      compared to those with NGT placement alone, and associated higher rates of
      institutionalization, medical complications, and long-term mortality. These
      findings may inform goals of care discussions and decisions regarding long-term
      tube feeding after acute stroke.

PMID- 29367445
TI  - Comparing nasogastric and direct tube feeding in stroke: Enteral feeding going
      down the tube.

PMID- 29367444
TI  - Neurofilament light protein in blood predicts regional atrophy in Huntington
      disease.
AB  - OBJECTIVE: Neurofilament light (NfL) protein in blood plasma has been proposed as
      a prognostic biomarker of neurodegeneration in a number of conditions, including
      Huntington disease (HD). This study investigates the regional distribution of NfL
      associated neural pathology in HD gene expansion carriers. METHODS: We examined
      associations between NfL measured in plasma and regionally specific atrophy in
      cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion
      carriers from the international multisite TRACK-HD study. Using voxel-based
      morphometry, we measured associations between baseline NfL levels and both
      baseline gray matter and white matter volume; and longitudinal change in gray
      matter and white matter over the subsequent 3 years in HD gene expansion
      carriers. RESULTS: After controlling for demographics, associations between
      increased NfL levels and reduced brain volume were seen in cortical and
      subcortical gray matter and within the white matter. After also controlling for
      known predictors of disease progression (age and CAG repeat length), associations
      were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent
      occipital gray matter atrophy and widespread white matter reduction, both before
      and after correction for other predictors of disease progression. CONCLUSIONS:
      These findings highlight the value of NfL as a dynamic marker of brain atrophy
      and, more generally, provide further evidence of the strong association between
      plasma NfL level, a candidate blood biomarker, and pathologic neuronal change.

PMID- 29367446
TI  - Zonisamide for DLB parkinsonism: An old drug used in a new context.

PMID- 29367447
TI  - Unraveling ALS due to SOD1 mutation through the combination of brain and cervical
      cord MRI.
AB  - OBJECTIVE: To explore structural and functional changes of the brain and cervical
      cord in patients with amyotrophic lateral sclerosis (ALS) due to mutation in the
      superoxide dismutase (SOD1) gene compared with sporadic ALS. METHODS: Twenty
      patients with SOD1 ALS, 11 with sporadic ALS, and 33 healthy controls underwent
      clinical evaluation and brain MRI. Cortical thickness analysis, diffusion tensor
      MRI of the corticospinal tracts (CST) and corpus callosum, and resting-state
      functional connectivity were performed. Patients with ALS also underwent cervical
      cord MRI to evaluate cord cross-sectional area and magnetization transfer ratio
      (MTR). RESULTS: Patients with SOD1 ALS showed longer disease duration and slower
      rate of functional decline relative to those with sporadic ALS. No cortical
      thickness abnormalities were found in patients with ALS compared with controls.
      Fractional anisotropy showed that sporadic ALS patients had significant CST
      damage relative to both healthy controls (p = 0.001-0.02) and SOD1-related ALS (p
      = 0.05), although the latter showed alterations that were intermediate between
      controls and sporadic ALS. Functional hyperconnectivity of the motor cortex in
      the sensorimotor network was observed in patients with sporadic ALS relative to
      controls. Conversely, patients with SOD1 ALS showed lower cord cross-sectional
      area along the whole cervical cord relative to those with sporadic ALS (p <
      0.001). No cord MTR differences were found between patient groups. CONCLUSIONS:
      Patients with SOD1 ALS showed cervical cord atrophy relative to those with
      sporadic ALS and a relative preservation of brain motor structural and functional
      networks. Neurodegeneration in SOD1 ALS is likely to occur primarily in the
      spinal cord. An objective and accurate estimate of spinal cord damage has
      potential in the future assessment of preventive SOD1 ALS therapies.

PMID- 29367448
TI  - Posthemorrhagic ventricular dilatation in preterm infants: When best to
      intervene?
AB  - OBJECTIVE: To compare neurodevelopmental outcomes of preterm infants with and
      without intervention for posthemorrhagic ventricular dilatation (PHVD) managed
      with an "early approach" (EA), based on ventricular measurements exceeding normal
      (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial
      temporizing procedures, followed, if needed, by permanent shunt placement, and a
      "late approach" (LA), based on signs of increased intracranial pressure with
      mostly immediate permanent intervention. METHODS: Observational cohort study of
      127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or
      LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was
      assessed at 18-24 months. RESULTS: Forty-nine of 78 (63%) EA and 24 of 49 (49%)
      LA infants received intervention. LA infants were slightly younger at birth, but
      did not differ from EA infants for other clinical measures. Initial intervention
      in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p <
      0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted
      predominantly of lumbar punctures or reservoir taps. Maximum VI in infants
      with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but
      differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p <
      0.001) and complications were lower in EA than LA group. Most EA infants had
      normal outcomes (>-1 SD), despite intervention. LA infants with intervention had
      poorer outcomes than those without (p < 0.003), with scores <-2 SD in 81%.
      CONCLUSION: In preterm infants with PHVD, those with early intervention, even
      when eventually requiring a shunt, had outcomes indistinguishable from those
      without intervention, all being within the normal range. In contrast, in infants
      managed with LA, need for intervention predicted worse outcomes. Benefits of EA
      appear to outweigh potential risks. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that for preterm infants with PHVD, an EA to
      management results in better neurodevelopmental outcomes than a LA.

PMID- 29367449
TI  - Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind
      phase 2 study.
AB  - OBJECTIVE: To investigate the efficacy and safety of zonisamide as an adjunct to
      levodopa therapy for parkinsonism in patients with dementia with Lewy bodies
      (DLB). METHODS: This phase 2, placebo-controlled, randomized, double-blind study
      consisted of run-in (placebo, 4 weeks) and treatment (placebo or zonisamide 25 or
      50 mg once daily, 12 weeks) periods. Outpatients diagnosed with probable DLB were
      eligible for inclusion. The primary endpoint was the change from baseline in
      Unified Parkinson's Disease Rating Scale (UPDRS) part 3 total score at week 12.
      Cognitive function, behavioral and psychological symptoms of dementia (BPSD),
      caregiver burden, other UPDRS parts as secondary endpoints, and safety were also
      assessed. RESULTS: Overall, 158 patients with DLB received the study drug; 21
      discontinued during treatment and 137 completed treatment. Improvement in UPDRS
      part 3 total score at week 12 was significantly greater in the zonisamide 50 mg
      group compared with placebo (between-group difference -4.1; 95% confidence
      interval -6.8 to -1.4; p = 0.003). Zonisamide did not worsen cognitive function,
      BPSD, or caregiver burden. The overall incidence of adverse events was higher in
      the zonisamide 50 mg than the 25 mg and placebo groups (65.3%, 43.1%, and 50.0%,
      respectively); similar rates of serious adverse events were observed among all
      groups. CONCLUSION: Zonisamide (adjunctive to levodopa) improved parkinsonism
      accompanying DLB without worsening cognitive function or psychiatric symptoms.
      CLINICAL TRIAL REGISTRATION: JapicCTI-122040. CLASSIFICATION OF EVIDENCE: This
      study provides Class I evidence that zonisamide (adjunctive to levodopa) improves
      parkinsonism and is well-tolerated in patients with DLB.

PMID- 29367450
TI  - A genotype-phenotype correlation for quantitative autistic trait burden in
      neurofibromatosis 1.

PMID- 29367451
TI  - Pleiotropic Functions of the Chromodomain-Containing Protein Hat-trick During
      Oogenesis in Drosophila melanogaster.
AB  - Chromatin-remodeling proteins have a profound role in the transcriptional
      regulation of gene expression during development. Here, we have shown that the
      chromodomain-containing protein Hat-trick is predominantly expressed within the
      oocyte nucleus, specifically within the heterochromatinized karyosome, and that a
      mild expression is observed in follicle cells. Colocalization of Hat-trick with
      Heterochromatin Protein 1 and synaptonemal complex component C(3)G along with the
      diffused karyosome after hat-trick downregulation shows the role of this protein
      in heterochromatin clustering and karyosome maintenance. Germline mosaic analysis
      reveals that hat-trick is required for maintaining the dorso-ventral patterning
      of eggs by regulating the expression of Gurken. The increased incidence of double
      strand breaks (DSBs), delayed DSB repair, defects in karyosome formation, altered
      Vasa mobility, and, consequently, misexpression and altered localization of
      Gurken in hat-trick mutant egg chambers clearly suggest a putative involvement of
      Hat-trick in the early stages of oogenesis. In addition, based on phenotypic
      observations in hat-trick mutant egg chambers, we speculate a substantial role of
      hat-trick in cystoblast proliferation, oocyte determination, nurse cell
      endoreplication, germ cell positioning, cyst encapsulation, and nurse cell
      migration. Our results demonstrate that hat-trick has profound pleiotropic
      functions during oogenesis in Drosophila melanogaster.

PMID- 29367454
TI  - Strong uniaxial magnetic anisotropy in Co films on highly ordered grating-like
      nanopatterned Ge surfaces.
AB  - We present a systematic investigation on uniaxial magnetic anisotropy (UMA) in Co
      thin films induced by high aspect ratio nanopatterned anisotropic substrates.
      Self-organized long grating-like nanostructures, with extreme regularities, are
      fabricated on Ge surfaces using Au-ion implantation at room temperature.
      Subsequently deposition of Co films are carried out on the same at two different
      angles. Magneto-optical Kerr effect measurements show strong UMA in Co films
      grown on ion-patterned Ge substrates, fabricated under different ion fluences,
      along and perpendicular to the direction of the patterns (long grating-like
      nanostructures). Magnetic force microscopy measurements under different
      externally applied magnetic fields reveal an easy domain wall motion when the
      field is applied along the grating-like nanostructures. On the other hand, high
      amplitude grating-like nanostructures hinder the spin rotation when the field is
      applied along the hard axis. The present study will be useful for magnetic
      recording media and ultra-small magnetic field sensors.

PMID- 29367452
TI  - Systematic Functional Characterization of Human 21st Chromosome Orthologs in
      Caenorhabditis elegans.
AB  - Individuals with Down syndrome have neurological and muscle impairments due to an
      additional copy of the human 21st chromosome (HSA21). Only a few of ~200 HSA21
      genes encoding proteins have been linked to specific Down syndrome phenotypes,
      while the remainder are understudied. To identify poorly characterized HSA21
      genes required for nervous system function, we studied behavioral phenotypes
      caused by loss-of-function mutations in conserved HSA21 orthologs in the nematode
      Caenorhabditis elegans We identified 10 HSA21 orthologs that are required for
      neuromuscular behaviors: cle-1 (COL18A1), cysl-2 (CBS), dnsn-1 (DONSON), eva-1
      (EVA1C), mtq-2 (N6ATM1), ncam-1 (NCAM2), pad-2 (POFUT2), pdxk-1 (PDXK), rnt-1
      (RUNX1), and unc-26 (SYNJ1). We also found that three of these genes are required
      for normal release of the neurotransmitter acetylcholine. This includes a known
      synaptic gene unc-26 (SYNJ1), as well as uncharacterized genes pdxk-1 (PDXK) and
      mtq-2 (N6ATM1). As the first systematic functional analysis of HSA21 orthologs,
      this study may serve as a platform to understand genes that underlie phenotypes
      associated with Down syndrome.

PMID- 29367456
TI  - We're listening.

PMID- 29367455
TI  - PKA signaling drives reticularis differentiation and sexually dimorphic adrenal
      cortex renewal.
AB  - The adrenal cortex undergoes remodeling during fetal and postnatal life. How zona
      reticularis emerges in the postnatal gland to support adrenarche, a process
      whereby higher primates increase prepubertal androgen secretion, is unknown.
      Using cell-fate mapping and gene deletion studies in mice, we show that
      activation of PKA has no effect on the fetal cortex, while it accelerates
      regeneration of the adult cortex, triggers zona fasciculata differentiation that
      is subsequently converted into a functional reticularis-like zone, and drives
      hypersecretion syndromes. Remarkably, PKA effects are influenced by sex. Indeed,
      testicular androgens increase WNT signaling that antagonizes PKA, leading to
      slower adrenocortical cell turnover and delayed phenotype whereas gonadectomy
      sensitizes males to hypercorticism and reticularis-like formation. Thus,
      reticularis results from ultimate centripetal conversion of adult cortex under
      the combined effects of PKA and cell turnover that dictate organ size. We show
      that PKA-induced progenitor recruitment is sexually dimorphic and may provide a
      paradigm for overrepresentation of women in adrenal diseases.

PMID- 29367457
TI  - Noninvasive gene delivery to foveal cones for vision restoration.
AB  - Intraocular injection of adeno-associated viral (AAV) vectors has been an evident
      route for delivering gene drugs into the retina. However, gaps in our
      understanding of AAV transduction patterns within the anatomically unique
      environments of the subretinal and intravitreal space of the primate eye impeded
      the establishment of noninvasive and efficient gene delivery to foveal cones in
      the clinic. Here, we establish new vector-promoter combinations to overcome the
      limitations associated with AAV-mediated cone transduction in the fovea with
      supporting studies in mouse models, human induced pluripotent stem cell-derived
      organoids, postmortem human retinal explants, and living macaques. We show that
      an AAV9 variant provides efficient foveal cone transduction when injected into
      the subretinal space several millimeters away from the fovea, without detaching
      this delicate region. An engineered AAV2 variant provides gene delivery to foveal
      cones with a well-tolerated dose administered intravitreally. Both delivery
      modalities rely on a cone-specific promoter and result in high-level transgene
      expression compatible with optogenetic vision restoration. The model systems
      described here provide insight into the behavior of AAV vectors across species to
      obtain safety and efficacy needed for gene therapy in neurodegenerative
      disorders.

PMID- 29367453
TI  - The life of U6 small nuclear RNA, from cradle to grave.
AB  - Removal of introns from precursor messenger RNA (pre-mRNA) and some noncoding
      transcripts is an essential step in eukaryotic gene expression. In the nucleus,
      this process of RNA splicing is carried out by the spliceosome, a multi
      megaDalton macromolecular machine whose core components are conserved from yeast
      to humans. In addition to many proteins, the spliceosome contains five uridine
      rich small nuclear RNAs (snRNAs) that undergo an elaborate series of
      conformational changes to correctly recognize the splice sites and catalyze
      intron removal. Decades of biochemical and genetic data, along with recent cryo
      EM structures, unequivocally demonstrate that U6 snRNA forms much of the
      catalytic core of the spliceosome and is highly dynamic, interacting with three
      snRNAs, the pre-mRNA substrate, and >25 protein partners throughout the splicing
      cycle. This review summarizes the current state of knowledge on how U6 snRNA is
      synthesized, modified, incorporated into snRNPs and spliceosomes, recycled, and
      degraded.

PMID- 29367459
TI  - Mutations causing congenital myasthenia reveal principal coupling pathway in the
      acetylcholine receptor epsilon-subunit.
AB  - We identify 2 homozygous mutations in the epsilon-subunit of the muscle
      acetylcholine receptor (AChR) in 3 patients with severe congenital myasthenia:
      epsilonR218W in the pre-M1 region in 2 patients and epsilonE184K in the beta8
      beta9 linker in 1 patient. Arg218 is conserved in all eukaryotic members of the
      Cys-loop receptor superfamily, while Glu184 is conserved in the alpha-, delta-,
      and epsilon-subunits of AChRs from all species. epsilonR218W reduces channel
      gating efficiency 338-fold and AChR expression on the cell surface 5-fold,
      whereas epsilonE184K reduces channel gating efficiency 11-fold but does not alter
      AChR cell surface expression. Determinations of the effective channel gating rate
      constants, combined with mutant cycle analyses, demonstrate strong energetic
      coupling between epsilonR218 and epsilonE184, and between epsilonR218 and
      epsilonE45 from the beta1-beta2 linker, as also observed for equivalent residues
      in the principal coupling pathway of the alpha-subunit. Thus, efficient and rapid
      gating of the AChR channel is achieved not only by coupling between conserved
      residues within the principal coupling pathway of the alpha-subunit, but also
      between corresponding residues in the epsilon-subunit.

PMID- 29367458
TI  - A pathophysiological role of PDE3 in allergic airway inflammation.
AB  - Phosphodiesterase 3 (PDE3) and PDE4 regulate levels of cyclic AMP, which are
      critical in various cell types involved in allergic airway inflammation. Although
      PDE4 inhibition attenuates allergic airway inflammation, reported side effects
      preclude its application as an antiasthma drug in humans. Case reports showed
      that enoximone, which is a smooth muscle relaxant that inhibits PDE3, is
      beneficial and lifesaving in status asthmaticus and is well tolerated. However,
      clinical observations also showed antiinflammatory effects of PDE3 inhibition. In
      this study, we investigated the role of PDE3 in a house dust mite-driven (HDM
      driven) allergic airway inflammation (AAI) model that is characterized by T
      helper 2 cell activation, eosinophilia, and reduced mucosal barrier function.
      Compared with wild-type (WT) littermates, mice with a targeted deletion of the
      PDE3A or PDE3B gene showed significantly reduced HDM-driven AAI. Therapeutic
      intervention in WT mice showed that all hallmarks of HDM-driven AAI were
      abrogated by the PDE3 inhibitors enoximone and milrinone. Importantly, we found
      that enoximone also reduced the upregulation of the CD11b integrin on mouse and
      human eosinophils in vitro, which is crucial for their recruitment during
      allergic inflammation. This study provides evidence for a hitherto unknown
      antiinflammatory role of PDE3 inhibition in allergic airway inflammation and
      offers a potentially novel treatment approach.

PMID- 29367460
TI  - IKKbeta is a beta-catenin kinase that regulates mesenchymal stem cell
      differentiation.
AB  - Mesenchymal stem cells (MSCs) can give rise to both adipocytes and osteoblasts,
      but the molecular mechanisms underlying MSC fate determination remain poorly
      understood. IkappaB kinase beta (IKKbeta), a central coordinator of inflammation
      and immune responses through activation of NF-kappaB, has been implicated as a
      critical molecular link between obesity and metabolic disorders. Here, we show
      that IKKbeta can reciprocally regulate adipocyte and osteoblast differentiation
      of murine and human MSCs through an NF-kappaB-independent mechanism. IKKbeta is a
      beta-catenin kinase that phosphorylates the conserved degron motif of beta
      catenin to prime it for beta-TrCP-mediated ubiquitination and degradation,
      thereby increasing adipogenesis and inhibiting osteogenesis in MSCs. Animal
      studies demonstrated that deficiency of IKKbeta in BM mesenchymal stromal cells
      increased bone mass and decreased BM adipocyte formation in adult mice. In
      humans, IKKbeta expression in adipose tissue was also positively associated with
      increased adiposity and elevated beta-catenin phosphorylation. These findings
      suggest IKKbeta as a key molecular switch that regulates MSC fate, and they
      provide potentially novel mechanistic insights into the understanding of the
      cross-regulation between the evolutionarily conserved IKKbeta and Wnt/beta
      catenin signaling pathways. The IKKbeta-Wnt axis we uncovered may also have
      important implications for development, homeostasis, and disease pathogenesis.

PMID- 29367461
TI  - CD122 blockade restores immunological tolerance in autoimmune type 1 diabetes via
      multiple mechanisms.
AB  - Signaling through IL-2/IL-15Rbeta (CD122) is essential for the differentiation
      and function of T cells and NK cells. A mAb against CD122 has been implicated to
      suppress autoimmune type 1 diabetes (T1D) development in animal models. However,
      the mechanisms remain poorly understood. We find that in vivo administration of
      an anti-CD122 mAb (CD122 blockade) restores immune tolerance in nonobese diabetic
      (NOD) mice via multiple mechanisms. First, CD122 blockade selectively ablates
      pathogenic NK cells and memory phenotype CD8+ T cells from pancreatic islets. In
      contrast, islet CD4+Foxp3+ Tregs are only mildly affected. Second, CD122 blockade
      suppresses IFN-gamma production in islet immune cells. Third, CD122 blockade
      inhibits the conversion of islet Th17 cells into diabetogenic Th1 cells.
      Furthermore, a combination of anti-CD122 mAb and Treg-trophic cytokines (IL-2 or
      IL-33) enhances the abundance and function of islet Tregs. In summary, these data
      provide crucial mechanistic insights into CD122 blockade-mediated
      immunoregulation and support therapeutic benefits of this combinational treatment
      in T1D.

PMID- 29367462
TI  - High self-reactivity drives T-bet and potentiates Treg function in tissue
      specific autoimmunity.
AB  - T cell receptor (TCR) affinity is a critical factor of Treg lineage commitment,
      but whether self-reactivity is a determining factor in peripheral Treg function
      remains unknown. Here, we report that a high degree of self-reactivity is crucial
      for tissue-specific Treg function in autoimmunity. Based on high expression of
      CD5, we identified a subset of self-reactive Tregs expressing elevated levels of
      T-bet, GITR, CTLA-4, and ICOS, which imparted significant protection from
      autoimmune diabetes. We observed that T-bet expression in Tregs, necessary for
      control of Th1 autoimmunity, could be induced in an IFNgamma-independent fashion
      and, unlike in conventional T cells (Tconv), was strongly correlated with the
      strength of TCR signaling. The level of CD5 similarly identified human Tregs with
      an increased functional profile, suggesting that CD5hi Tregs may constitute an
      efficacious subpopulation appropriate for use in adoptive Treg therapies for
      treatment of inflammatory conditions. Overall, this work establishes an
      instrumental role of high TCR self-reactivity in driving Treg function.

PMID- 29367463
TI  - Mutant p53R270H drives altered metabolism and increased invasion in pancreatic
      ductal adenocarcinoma.
AB  - Pancreatic cancer is characterized by nearly universal activating mutations in
      KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human
      pancreatic tumors. Genetically engineered mice have proven instrumental in
      studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras
      mutations occur early during pancreatic carcinogenesis and are considered an
      initiating event. In contrast, mutations in p53 occur later during tumor
      progression. In our model, we recapitulated the order of mutations of the human
      disease, with p53 mutation following expression of oncogenic Kras. Further, using
      an inducible and reversible expression allele for mutant p53, we inactivated its
      expression at different stages of carcinogenesis. Notably, the function of mutant
      p53 changes at different stages of carcinogenesis. Our work establishes a
      requirement for mutant p53 for the formation and maintenance of pancreatic cancer
      precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However,
      it maintains the altered metabolism that characterizes pancreatic cancer and
      mediates its malignant potential. Further, mutant p53 promotes epithelial
      mesenchymal transition (EMT) and cancer cell invasion. This work generates new
      mouse models that mimic human pancreatic cancer and expands our understanding of
      the role of p53 mutation, common in the majority of human malignancies.

PMID- 29367464
TI  - Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung
      endothelial injury.
AB  - Primary graft dysfunction (PGD) is acute lung injury within 72 hours of lung
      transplantation. We hypothesized that cell-free hemoglobin (CFH) contributes to
      PGD by increasing lung microvascular permeability and tested this in patients, ex
      vivo human lungs, and cultured human lung microvascular endothelial cells. In a
      nested case control study of 40 patients with severe PGD at 72 hours and 80
      matched controls without PGD, elevated preoperative CFH was independently
      associated with increased PGD risk (odds ratio [OR] 2.75, 95%CI, 1.23-6.16, P =
      0.014). The effect of CFH on PGD was magnified by reperfusion fraction of
      inspired oxygen (FiO2) >= 0.40 (OR 3.41, P = 0.031). Isolated perfused human
      lungs exposed to intravascular CFH (100 mg/dl) developed increased vascular
      permeability as measured by lung weight (CFH 14.4% vs. control 0.65%, P = 0.047)
      and extravasation of Evans blue-labeled albumin dye (EBD) into the airspace (P =
      0.027). CFH (1 mg/dl) also increased paracellular permeability of human pulmonary
      microvascular endothelial cell monolayers (hPMVECs). Hyperoxia (FiO2 = 0.95)
      increased human lung and hPMVEC permeability compared with normoxia (FiO2 =
      0.21). Treatment with acetaminophen (15 MUg/ml), a specific hemoprotein
      reductant, prevented CFH-dependent permeability in human lungs (P = 0.046) and
      hPMVECs (P = 0.037). In summary, CFH may mediate PGD through oxidative effects on
      microvascular permeability, which are augmented by hyperoxia and abrogated by
      acetaminophen.

PMID- 29367465
TI  - Inflammatory macrophage-associated 3-gene signature predicts subclinical
      allograft injury and graft survival.
AB  - Late allograft failure is characterized by cumulative subclinical insults
      manifesting over many years. Although immunomodulatory therapies targeting host T
      cells have improved short-term survival rates, rates of chronic allograft loss
      remain high. We hypothesized that other immune cell types may drive subclinical
      injury, ultimately leading to graft failure. We collected whole-genome
      transcriptome profiles from 15 independent cohorts composed of 1,697 biopsy
      samples to assess the association of an inflammatory macrophage polarization
      specific gene signature with subclinical injury. We applied penalized regression
      to a subset of the data sets and identified a 3-gene inflammatory macrophage
      derived signature. We validated discriminatory power of the 3-gene signature in 3
      independent renal transplant data sets with mean AUC of 0.91. In a longitudinal
      cohort, the 3-gene signature strongly correlated with extent of injury and
      accurately predicted progression of subclinical injury 18 months before clinical
      manifestation. The 3-gene signature also stratified patients at high risk of
      graft failure as soon as 15 days after biopsy. We found that the 3-gene signature
      also distinguished acute rejection (AR) accurately in 3 heart transplant data
      sets but not in lung transplant. Overall, we identified a parsimonious signature
      capable of diagnosing AR, recognizing subclinical injury, and risk-stratifying
      renal transplant patients. Our results strongly suggest that inflammatory
      macrophages may be a viable therapeutic target to improve long-term outcomes for
      organ transplantation patients.

PMID- 29367467
TI  - Lymphatic function measurements influenced by contrast agent volume and body
      position.
AB  - Several imaging modalities have been used to assess lymphatic function, including
      fluorescence microscopy, near-infrared fluorescence (NIRF) imaging, and Doppler
      optical coherence tomography (DOCT). They vary in how the mouse is positioned,
      the invasiveness of the experimental setup, and the volume of contrast agent
      injected. Here, we present how each of these experimental parameters affects
      functional measurements of collecting lymphatic vessels. First, fluorescence
      microscopy showed that supine mice have a statistically lower contraction
      frequency compared with mice sitting upright. To assess the effect of different
      injection volumes on these endpoints, mice were injected with 4, 10, or 20 MUl of
      dye. The lowest frequencies were observed after 20-MUl injections. Interestingly,
      lymph-flow DOCT revealed that although there was lower contraction frequency in
      mice injected with 20 MUl versus 4 MUl, mice showed a higher volumetric flow with
      a 20-MUl injection. This indicates that contraction frequency alone is not
      sufficient to understand lymphatic transport. Finally, NIRF revealed that
      removing the skin reduced contraction frequency. Therefore, this study reveals
      how sensitive these techniques are to mouse position, removal of skin, and dye
      volume. Care should be taken when comparing results obtained under different
      experimental conditions.

PMID- 29367466
TI  - Mutations in Hnrnpa1 cause congenital heart defects.
AB  - Incomplete penetrance of congenital heart defects (CHDs) was observed in a mouse
      model. We hypothesized that the contribution of a major genetic locus modulates
      the manifestation of the CHDs. After genome-wide linkage mapping, fine mapping,
      and high-throughput targeted sequencing, a recessive frameshift mutation of the
      heterogeneous nuclear ribonucleoprotein A1 (Hnrnpa1) gene was confirmed
      (Hnrnpa1ct). Hnrnpa1 was expressed in both the first heart field (FHF) and second
      heart field (SHF) at the cardiac crescent stage but was only maintained in SHF
      progenitors after heart tube formation. Hnrnpa1ct/ct homozygous mutants displayed
      complete CHD penetrance, including truncated and incomplete looped heart tube at
      E9.5, ventricular septal defect (VSD) and persistent truncus arteriosus (PTA) at
      E13.5, and VSD and double outlet right ventricle at P0. Impaired development of
      the dorsal mesocardium and sinoatrial node progenitors was also observed. Loss of
      Hnrnpa1 expression leads to dysregulation of cardiac transcription networks and
      multiple signaling pathways, including BMP, FGF, and Notch in the SHF. Finally,
      two rare heterozygous mutations of HNRNPA1 were detected in human CHDs. These
      findings suggest a role of Hnrnpa1 in embryonic heart development in mice and
      humans.

PMID- 29367468
TI  - DNA methylation signatures reflect aging in patients with nonalcoholic
      steatohepatitis.
AB  - A DNA methylation (DNAm) signature (the "Horvath clock") has been proposed as a
      measure of human chronological and biological age. We determined peripheral blood
      DNAm in patients with nonalcoholic steatohepatitis (NASH) and assessed whether
      accelerated aging occurs in these patients. DNAm signatures were obtained in
      patients with biopsy-proven NASH and stage 2-3 fibrosis. The DNAm profile from
      one test and two validation cohorts served as controls. Age acceleration was
      calculated as the difference between DNAm age and the predicted age based on the
      linear model derived from controls. Hepatic collagen content was assessed by
      quantitative morphometry. The Horvath clock accurately predicts the chronological
      age of the entire cohort. Age acceleration was observed among NASH subjects
      compared with control data sets and our test controls. Age acceleration in NASH
      subjects did not differ by fibrosis stage but correlated with hepatic collagen
      content. A set of 152 differentially methylated CpG islands between NASH subjects
      and controls identified gene set enrichment for transcription factors and
      developmental pathways. Patients with NASH exhibit epigenetic age acceleration
      that correlates with hepatic collagen content.

PMID- 29367470
TI  - Minimally Invasive Surgical Approach to Filum Lipoma.
AB  - Filum terminale lipoma (FTL) causes various spinal symptoms known as tethered
      cord syndrome. The treatment for FTL is surgical untethering by sectioning the
      FTL, which can prevent symptom progression and often results in improvement of
      symptoms. This report describes a minimally invasive surgical strategy that we
      have introduced for FTL sectioning. The pediatric patients with FTL since 2007
      were treated using this minimally invasive surgical strategy, which we refer to
      as an interlaminar approach (ILA). In summary, the surgical technique involves:
      minimal skin incision to expose the unilateral ligamentum flavum in the lower
      lumbar region; ligamentum flavum incision to expose the dural sac, and dural
      incision followed by identification and sectioning of the filum. Postoperatively,
      no bed rest was required. Prior to introducing ILA, we had used standard one
      level laminectomy/laminotomy (LL) with more than 1 week of postsurgical bed rest
      until 2007, providing an adequate control group for the benefit of the ILA. A
      total of 49 consecutive patients were treated using ILA. While 37 patients were
      treated using LL. Surgical complications that need surgery were seen only in one
      patient, who developed cerebrospinal fluid (CSF) leak in LL patients. No
      retethering or additional neurological symptoms were seen during follow-up. All
      patients complained of minimal postsurgical back pain, but no patients required
      postoperative bed rest in ILA patients, while LL patients need postsurgical bed
      rest because of back pain. The ILA strategy provides the advantage of a minimal
      tissue injury, associated with minimal postoperative pain, blood loss, and bed
      rest.

PMID- 29367469
TI  - cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific
      germinal center responses.
AB  - Sensing of pathogens by host pattern recognition receptors is essential for
      activating the immune response during infection. We used a nonlethal murine model
      of malaria (Plasmodium yoelii 17XNL) to assess the contribution of the pattern
      recognition receptor cyclic GMP-AMP synthase (cGAS) to the development of humoral
      immunity. Despite previous reports suggesting a critical, intrinsic role for cGAS
      in early B cell responses, cGAS-deficient (cGAS-/-) mice had no defect in the
      early expansion or differentiation of Plasmodium-specific B cells. As the
      infection proceeded, however, cGAS-/- mice exhibited higher parasite burdens and
      aberrant germinal center and memory B cell formation when compared with
      littermate controls. Antimalarial drugs were used to further demonstrate that the
      disrupted humoral response was not B cell intrinsic but instead was a secondary
      effect of a loss of parasite control. These findings therefore demonstrate that
      cGAS-mediated innate-sensing contributes to parasite control but is not
      intrinsically required for the development of humoral immunity. Our findings
      highlight the need to consider the indirect effects of pathogen burden in
      investigations examining how the innate immune system affects the adaptive immune
      response.

PMID- 29367471
TI  - Effects of linagliptin monotherapy compared with voglibose on postprandial lipid
      profiles in Japanese patients with type 2 diabetes: linagliptin study of effects
      on postprandial blood glucose (L-STEP) sub-study 1.
AB  - Recently, we reported that linagliptin had equivalent efficacy to voglibose in
      reducing postprandial blood glucose levels in drug-naive patients with type 2
      diabetes (L-STEP Study). As a sub-study of the L-STEP Study we examined the
      effect of linagliptin on postprandial lipids profile. Between October 2012 and
      April 2014, the study enrolled patients with type 2 diabetes mellitus who had
      inadequate glycemic control. Patients were randomly assigned to either the
      linagliptin group (5 mg once daily, n = 85) or the voglibose group (0.2 mg/meal
      thrice daily, n = 71). Meal tolerance tests were performed at baseline (week 0)
      and endpoint (week 12). The increments in 4-h postprandial triglyceride, remnant
      lipoprotein cholesterol (RLP-C), and apolipoprotein B48 (ApoB48) from baseline to
      endpoint in the linagliptin group were lower (p < 0.001, p = 0.025 and p <
      0.001). 4-h postprandial ApoB48 at endpoint was lower in the linagliptin group (p
      = 0.007), and positive correlation was detected between change of ApoB48 and
      changes in both triglyceride (r = 0.67, p < 0.001) and RLP-C (r = 0.73, p <
      0.001) at 4 h. This study revealed that in drug-naive Japanese patients with
      relatively mild type 2 diabetes mellitus, linagliptin improves not only
      postprandial blood glucose level but also levels of lipids such as TG and RLP-C
      by reducing the ApoB48 level compared with voglibose.

PMID- 29367472
TI  - Host-Symbiont Cospeciation of Termite-Gut Cellulolytic Protists of the Genera
      Teranympha and Eucomonympha and their Treponema Endosymbionts.
AB  - Cellulolytic flagellated protists inhabit the hindgut of termites. They are
      unique and essential to termites and related wood-feeding cockroaches, enabling
      host feeding on cellulosic matter. Protists of two genera in the family
      Teranymphidae (phylum Parabasalia), Eucomonympha and Teranympha, are
      phylogenetically closely related and harbor intracellular endosymbiotic bacteria
      from the genus Treponema. In order to obtain a clearer understanding of the
      evolutionary history of this triplex symbiotic relationship, the molecular
      phylogenies of the three symbiotic partners, the Teranymphidae protists, their
      Treponema endosymbionts, and their host termites, were inferred and compared.
      Strong congruence was observed in the tree topologies of all interacting
      partners, implying their cospeciating relationships. In contrast, the
      coevolutionary relationship between the Eucomonympha protists and their
      endosymbionts was more complex, and evidence of incongruence against cospeciating
      relationships suggested frequent host switches of the endosymbionts, possibly
      because multiple Eucomonympha species are present in the same gut community.
      Similarities in the 16S rRNA and gyrB gene sequences of the endosymbionts were
      higher among Teranympha spp. (>99.25% and >97.2%, respectively), whereas those
      between Teranympha and Eucomonympha were lower (<97.1% and <91.9%, respectively).
      In addition, the endosymbionts of Teranympha spp. formed a phylogenetic clade
      distinct from those of Eucomonympha spp. Therefore, the endosymbiont species of
      Teranympha spp., designated here as "Candidatus Treponema teratonymphae", needs
      to be classified as a species distinct from the endosymbiont species of
      Eucomonympha spp.

PMID- 29367474
TI  - Cullin-associated NEDD8-dissociated protein 1, a novel interactor of rabphilin
      3A, deubiquitylates rabphilin-3A and regulates arginine vasopressin secretion in
      PC12 cells.
AB  - The molecular mechanism involved in the exocytosis of arginine vasopressin (AVP)
      is not fully known. Rabphilin-3A has been suggested as a novel autoantigen in
      infundibulo-neurohypophysitis (LINH), which leads to central diabetes insipidus
      through insufficient secretion of AVP. However, the role of rabphilin-3A in the
      pathogenesis of LINH remains unclear. Thus, the aim of the present study was to
      identify proteins binding rabphilin-3A in the posterior pituitary. Using
      glutathione S-transferase (GST)-pulldown assays and proteomic analyses, cullin
      associated NEDD8-dissociated protein 1 (CAND1) was identified as a rabphilin-3A
      binding protein in the posterior pituitary. Co-immunoprecipitation assays
      indicated that CAND1 interacted endogenously with rabphilin-3A. In addition,
      immunohistochemistry experiments showed that CAND1 immunoreactivity was detected
      mainly in the posterior pituitary, intermediate lobe, and the supraoptic nucleus
      in the hypothalamus, and less in the anterior lobe, partially co-localizing with
      rabphilin-3A. Overexpression of CAND1 resulted in deubiquitylation of rabphilin
      3A in PC12 cells. Moreover, overexpression of CAND1 in PC12 cells co-transfected
      with AVP enhanced both basal and KCl-stimulated AVP secretion. The findings
      indicate that CAND1 inhibits the ubiquitylation of rabphilin-3A and positively
      regulates AVP secretion. These data shed light on a novel potential mechanism
      involving rabphilin-3A in AVP secretion, and suggest a new role of CAND1 as a
      regulator of hormone or neurotransmitter secretion.

PMID- 29367473
TI  - Nitrogen Fixation in Thermophilic Chemosynthetic Microbial Communities Depending
      on Hydrogen, Sulfate, and Carbon Dioxide.
AB  - The activity of nitrogen fixation measured by acetylene reduction was examined in
      chemosynthetic microbial mats at 72-75 degrees C in slightly-alkaline sulfidic
      hot springs in Nakabusa, Japan. Nitrogenase activity markedly varied from
      sampling to sampling. Nitrogenase activity did not correlate with methane
      production, but was detected in samples showing methane production levels less
      than the maximum amount, indicating a possible redox dependency of nitrogenase
      activity. Nitrogenase activity was not affected by 2-bromo-ethane sulfonate, an
      inhibitor of methanogenesis. However, it was inhibited by the addition of
      molybdate, an inhibitor of sulfate reduction and sulfur disproportionation,
      suggesting the involvement of sulfate-reducing or sulfur-disproportionating
      organisms. Nitrogenase activity was affected by different O2 concentrations in
      the gas phase, again supporting the hypothesis of a redox potential dependency,
      and was decreased by the dispersion of mats with a homogenizer. The loss of
      activity that occurred from dispersion was partially recovered by the addition of
      H2, sulfate, and carbon dioxide. These results suggested that the observed
      activity of nitrogen fixation was related to chemoautotrophic sulfate reducers,
      and fixation may be active in a limited range of ambient redox potential. Since
      thermophilic chemosynthetic communities may resemble ancient microbial
      communities before the appearance of photosynthesis, the present results may be
      useful when considering the ancient nitrogen cycle on earth.

PMID- 29367475
TI  - Triggering of Autophagy by Baicalein in Response to Apoptosis after Spinal Cord
      Injury: Possible Involvement of the PI3K Activation.
AB  - High level apoptosis induced by spinal cord injury (SCI) evokes serious damage
      because of the loss and dysfunction of motor neurons. Our previous studies showed
      that inhibition of autophagy evokes the activation of apoptosis. Interestingly,
      Baicalein, a medicine with anti-apoptosis activity that is derived from the roots
      of herb Scutellaria baicalensis, largely induces autophagy by activating
      phosphatidylinositol 3-kinase (PI3K). In this study, we investigated the effects
      of intraperitoneal injection of Baicalein on autophagy and apoptosis in SCI mice
      and evaluated the relationship between autophagy and apoptosis. We demonstrated
      that Baicalein promoted the functional recovery of motor neurons at 7 d after
      SCI. In addition, Baicalein enhanced neuronal autophagy and the autophagy-related
      factor PI3K, while inhibiting the p62 protein. Baicalein treatment decreased
      neuronal apoptosis at 7 d after SCI. Moreover, when inhibiting autophagy,
      apoptosis was upgraded by Baicalein treatment after injury. Thus, Baicalein
      attenuated SCI by inducing autophagy to reduce apoptosis in neurons potentially
      via activating PI3K.

PMID- 29367476
TI  - Cardiovascular Structural Interventions - Echo/Computed Tomography-Fluoroscopy
      Fusion Imaging Atlas.

PMID- 29367477
TI  - Neoatherosclerosis With Napkin Ring Calcification.

PMID- 29367478
TI  - Ultrasonic-assisted Aqueous Extraction and Physicochemical Characterization of
      Oil from Clanis bilineata.
AB  - Ultrasound-assisted aqueous extraction (UAAE) was used to extract oil from Clanis
      bilineata (CB), a traditional edible insect that can be reared on a large scale
      in China, and the physicochemical property and antioxidant capacity of the UAAE
      derived oil (UAAEO) were investigated for the first time. UAAE conditions of CB
      oil was optimized using response surface methodology (RSM) and the highest oil
      yield (19.47%) was obtained under optimal conditions for ultrasonic power,
      extraction temperature, extraction time, and ultrasonic interval time at 400 W,
      40 degrees C, 50 min, and 2 s, respectively. Compared with Soxhlet extraction
      derived oil (SEO), UAAEO had lower acid (AV), peroxide (PV) and p-anisidine
      values (PAV) as well as higher polyunsaturated fatty acids contents and thermal
      stability. Furthermore, UAAEO showed stronger antioxidant activities than those
      of SEO, according to DPPH radical scavenging and beta-carotene bleaching tests.
      Therefore, UAAE is a promising process for the large-scale production of CB oil
      and CB has a developing potential as functional oil resource.

PMID- 29367479
TI  - Development of gamma-Oryzanol Rich Extract from Leum Pua Glutinous Rice Bran
      Loaded Nanostructured Lipid Carriers for Topical Delivery.
AB  - Leum Pua is native Thai glutinous rice that contains antioxidants higher than
      white rice and other colored rice. One of the major antioxidants in rice brans is
      gamma-oryzanol (GO). In this study, Leum Pua glutinous rice bran was extracted by
      different solvents. Oleic acid (~40 g/100 g extract), linoleic acid (~30 g/100 g
      extract), and palmitic acid (~20 g/100 g extract) were found to be major lipid
      components in the extracts. Methanol extract showed less variety of lipid
      components compared to the others. However, hexane extract showed the highest
      percent of gamma-oryzanol compared to other solvents. Therefore, the hexane
      extract was selected to prepare nanostructured lipid carriers (NLC). The prepared
      NLC had small particles in the size range of 142.9 +/- 0.4 nm for extract-loaded
      NLC and 137.1 +/- 0.5 nm for GO-loaded NLC with narrow size distribution (PI <
      0.1) in both formulations. The release profile of extract-loaded NLC formulation
      was slightly higher than GO-loaded NLC formulation. However, they did not follow
      the Higuchi model because of small amounts of gamma-oryzanol loaded in NLC
      particles.

PMID- 29367480
TI  - Effects of Extraction Methods on Phytochemicals of Rice Bran Oils Produced from
      Colored Rice.
AB  - Rice bran oil (RBO) especially from colored rice is rich in phytochemicals and
      has become popular in food, cosmetic, nutraceutical and pharmaceutical
      applications owing to its offering health benefits. This study determined the
      contents of phytochemicals including oryzanols, phytosterols, tocopherols (Toc)
      and tocotrienols (T3) in RBOs extracted using different methods namely cold-press
      extraction (CPE), solvent extraction (SE) and supercritical CO2 extraction (SC
      CO2). Two colored rice, Red Jasmine rice (RJM, red rice) and Hom-nin rice (HN,
      black rice), were studied in comparison with the popular Thai fragrant rice Khao
      Dawk Mali 105 (KDML 105, white rice). RBOs were found to be the rich source of
      oryzanols, phytosterols, Toc and T3. Rice varieties had a greater effect on the
      phytochemicals concentrations than extraction methods. HN rice showed the
      significantly highest concentration of all phytochemicals, followed by RJM and
      KDML 105 rice, indicating that colored rice contained high concentration of
      phytochemicals in the oil than non-colored rice. The RBO samples extracted by the
      CPE method had a greater concentration of the phytochemicals than those extracted
      by the SC-CO2 and SE methods, respectively. In terms of phytochemical contents,
      HN rice extracted using CPE method was found to be the best.

PMID- 29367481
TI  - Laundry Detergency of Solid Non-Particulate Soil Using Microemulsion-Based
      Formulation.
AB  - Laundry detergency of solid non-particulate soil on polyester and cotton was
      investigated using a microemulsion-based formulation, consisting of an anionic
      extended surfactant (C12,13-4PO-SO4Na) and sodium mono-and di-methyl naphthalene
      sulfonate (SMDNS) as the hydrophilic linker, to provide a Winsor Type III
      microemulsion with an ultralow interfacial tension (IFT). In this work, methyl
      palmitate (palmitic acid methyl ester) having a melting point around 30 degrees
      C, was used as a model solid non-particulate (waxy) soil. A total surfactant
      concentration of 0.35 wt% of the selected formulation (4:0.65 weight ratio of
      C12,13-4PO-SO4Na:SMDNS) with 5.3 wt% NaCl was able to form a middle phase
      microemulsion at a high temperature (40 degrees C),which provided the highest oil
      removal level with the lowest oil redeposition and the lowest IFT, and was much
      higher than that with a commercial detergent or de-ionized water. Most of the
      detached oil, whether in liquid or solid state, was in an unsolubilized form.
      Hence, the dispersion stability of the detached oil droplets or solidified oil
      particles that resulted from the surfactant adsorption played an important role
      in the oil redeposition. For an oily detergency, the lower the system IFT, the
      higher the oil removal whereas for a waxy (non-particulate) soil detergency, the
      lower the contact angle, the higher the solidified oil removal. For a liquefied
      oil, the detergency mechanism was roll up and emulsification with dispersion
      stability, while that for the waxy soil (solid oil) was the detachment by
      wettability with dispersion stability.

PMID- 29367482
TI  - Value-addition of Beef Meat By-products: Lipid Characterization by
      Chromatographic Techniques.
AB  - The lipid characterization of storage fat, subcutaneous fat and bone marrow,
      originated from three different bovine categories, calf, young bull and cow, was
      carried out in order to develop a re-use of these by-products. After the lipid
      extraction, the compositions in fatty acids, triacylglycerols and cholesterol
      were determined by GC-FID. A total of 25 fatty acids were identified in all by
      products; the oleic acid was the preponderant component, followed by palmitic,
      stearic, palmitoleic, linoleic and myristic acid. The long chain triacylglycerols
      (T48, T50 and T52) were the main products, especially in the cow's by-products.
      The subcutaneous fat of all animals showed the highest cholesterol content,
      whereas it was present in low amount in the others. Phospholipids were analysed
      in bone marrow of all the animals and phosphatidylcholine was the most abundant
      compound. Because of the high fat content and essential fatty acids and the low
      cholesterol amount, storage fat and bone marrow could represent a valuable lipid
      resource in food and pharmaceutical industry.

PMID- 29367483
TI  - Effect of Alcohols on the Phase Behavior and Emulsification of a Sucrose Fatty
      Acid Ester/Water/Edible Oil System.
AB  - The effect of alcohols (ethanol, 1-propanol, propylene glycol, glycerin, sucrose)
      on the phase behavior and emulsification of sucrose stearic acid ester
      (SSE)/water/edible vegetable oil (EVO) systems was investigated. Adding sucrose,
      propylene glycol, and glycerin narrowed the oil-separated two-phase region in the
      phase diagram of the SSE/water/EVO systems, whereas adding ethanol and 1-propanol
      expanded the oil-separated two-phase region. Changing the course of
      emulsification in the phase diagram showed that the size of the oil-droplet
      particle typically decreased in a system with a narrowed oil-separated region.
      The emulsification properties of the systems varied with respect to changes in
      the phase diagram. The microstructure of the systems was examined using small
      angle X-ray scattering, and the ability to retain the oil in the lamellar
      structure of the SSEs was suggested as an important role in emulsification,
      because the mechanism of the systems was the same as that for the liquid crystal
      emulsification method.

PMID- 29367484
TI  - Preparation of Chiral Triacylglycerols, sn-POO and sn-OOP, via Lipase-mediated
      Acidolysis Reaction.
AB  - It is well known that lipases are useful tools for preparing various structured
      triacylglycerols (TAGs). However, the lipase-mediated preparation of chiral TAGs
      has never been reported. This study aimed to prepare chiral TAGs (viz., 1
      palmitoyl-2,3-dioleoyl-sn-glycerol (sn-POO) or 1,2-dioleoyl-3-palmitoyl-sn
      glycerol (sn-OOP)) via lipase mediated acidolysis, using triolein (TO) and
      palmitic acid (P) as substrates. Three commercially available lipases (viz.,
      Lipozyme RM-IM(r), Lipozyme TL-IM(r), and Lipase OF(r)) were used. Lipozyme RM
      IM(r) resulted in an increase 1P-2O (sn-POO + sn-OOP + 1,3-dioleoyl-2-palmitoyl
      sn-glycerol) content with reaction time, which plateaued at 2~24 h (max. yield
      47.1% at 4 h). The highest sn-POO/sn-OOP ratio of ca. 9 was obtained at 0.25 h,
      and the rate got close to 1 with reaction time (sn-POO/sn-OOP = 1.3 at 24 h).
      Lipozyme TL-IM(r) resulted in a lower 1P-2O synthesis rate than Lipozyme RM
      IM(r), where its highest sn-POO/sn-OOP ratio of ca. 2 was obtained at 0.25 h and
      did not vary much further with reaction time. In the case of Lipase OF(r), its
      reaction rate for 1P-2O synthesis was lower than that of the other two lipases,
      and the highest sn-POO/sn-OOP ratio of ca. 1.4 was obtained at 0.5 h, reaching
      closer to 1 with a longer reaction time. Reaction solvents (viz., hexane,
      acetone, and benzene) also affected the 1P-2O preparation, where the highest 1P
      2O content was obtained with the solvent-free system. Furthermore, the solvent
      free system showed a higher reaction rate for 1P-2O synthesis than did the hexane
      system, with no effect on chiral specificity of the lipase for the TAG molecules.
      These results suggested that among three types of commercial lipase, Lipozyme RM
      IM(r) is the most useful for the preparation of chiral TAGs by acidolysis
      reaction.

PMID- 29367485
TI  - Safety Evaluation and Plasma Carotenoid Accumulation in Healthy Adult Subjects
      after 12 Weeks of Paprika Oleoresin Supplementation.
AB  - Paprika oleoresin is obtained by solvent extraction from Capsicum annuum L.
      fruits and contains multiple carotenoids, such as capsanthin, beta-carotene,
      zeaxanthin, and beta-cryptoxanthin, which are considered protective against
      various diseases. Herein, we investigated the effect of paprika oleoresin
      supplementation on plasma carotenoid accumulation and evaluated the safety of the
      oleoresin. We used a double-blinded, placebo-controlled comparative clinical
      study design and tested the effects of varying doses in healthy adult subjects.
      In total, 33 subjects were randomly divided into three groups to take capsules
      containing 0, 20, or 100 mg of paprika oleoresin daily for 12 consecutive weeks.
      Plasma carotenoid concentrations were measured at 0, 4, 8, and 12 weeks, and the
      safety of paprika oleoresin capsules was investigated using analyses of blood
      biochemistry, hematology, and urine contents. In these experiments, beta
      cryptoxanthin and zeaxanthin dose-dependently accumulated in plasma within the
      dose range of the study over 12 consecutive weeks of paprika oleoresin
      supplementation. Moreover, beta-cryptoxanthin accumulated to higher levels than
      the other paprika oleoresin carotenoids. In contrast, capsanthin was not detected
      in plasma before or during the 12-week treatment period. Finally, no adverse
      events were associated with intake of paprika oleoresin (20 and 100 mg/day) in
      safety evaluations. Paprika oleoresin is a suitable source of carotenoids,
      especially beta-cryptoxanthin.

PMID- 29367486
TI  - Improvement of Diet-induced Obesity by Ingestion of Mushroom Chitosan Prepared
      from Flammulina velutipes.
AB  - The anti-obesity effects of mushroom chitosan prepared from Flammulina velutipes
      were investigated using an animal model with diet-induced obesity. In this study,
      5-week-old imprinting control region (ICR) mice were divided into six groups of
      10 mice each and fed different diets based on the MF powdered diet (standard
      diet) for 6 weeks: standard diet control group, high-fat diet control group
      (induced dietary obesity) consisting of the standard diet and 20% lard, and
      mushroom chitosan groups consisting of the high-fat diet with mushroom chitosan
      added at 100, 500, 1,000, and 2,000 mg/kg body weight. On the final day of the
      experiment, mean body weight was 39.1 g in the high-fat control group and 36.3 g
      in the 2,000 mg/kg mushroom chitosan group, compared to 35.8 g in the standard
      diet control group. In the mushroom chitosan groups, a dose-dependent suppression
      of weight gain and marked improvements in serum triglycerides, total cholesterol,
      LDL-cholesterol, and HDL-cholesterol were found. The mushroom chitosan groups
      showed fewer and smaller fat deposits in liver cells than the high-fat diet
      control group, and liver weight was significantly reduced. Glutamic oxaloacetic
      transaminase (GOT) and glutamate pyruvic transaminase (GPT), which are indices of
      the hepatic function, all showed dose-dependent improvement with mushroom
      chitosan administration. These results suggested that mushroom chitosan acts to
      suppress enlargement of the liver from fat deposition resulting from a high-fat
      diet and to restore hepatic function. The lipid content of feces showed a marked
      increase correlated with the mushroom chitosan dose. These findings suggest the
      potential use of mushroom chitosan as a functional food ingredient that
      contributes to the prevention or improvement of dietary obesity by inhibiting
      digestion and absorption of fats in the digestive tract and simultaneously
      promotes lipolysis in adipocytes.

PMID- 29367487
TI  - Optimization of Enzymatic Cell Disruption for Improving Lipid Extraction from
      Schizochytrium sp. through Response Surface Methodology.
AB  - This study is aimed to explore the optimal conditions of cell disruption in the
      extraction algae oil process, using alkaline protease to disrupt cell of
      Schizochytrium sp. to extract oil in this paper. The effects of enzymatic lysis
      temperature, enzymatic lysis time, enzyme dosage and pH value on oil yield and
      DHA yield were studied. Through the combination of single factor test and
      response surface design, the optimal cell disruption conditions were screened
      out. The fatty acid composition of algal oil was analyzed by gas chromatography
      massspectrometry (GC-MS). The results showed that when the conditions were:
      enzymatic lysis temperature 55 degrees C, enzymatic lysis time 9 h, enzyme dosage
      3% of biomass and pH 8,oil yield and DHA yield reached the highest 14.52 g/L and
      7.12 g/L, respectively. When the strains were cultured in 50 L fermentor, oil
      yield reached 26.27 g/L and DHA yield reached 12.89 g/L. They were 1.81 times
      higher than that in shake-flask cultivation. The optimization experiment provides
      the basis for the industrial production of Schizochytrium sp.

PMID- 29367488
TI  - Production of Ethylene through Ethanol Dehydration on SBA-15 Catalysts
      Synthesized by Sol-gel and One-step Hydrothermal Methods.
AB  - The present work deals with the catalytic performance of SBA-15 supported
      catalysts in the gas phase catalytic dehydration of ethanol in the temperature
      range of 200 to 400 degrees C. The SBA-15 support was incorporated on a zirconium
      (Zr) and bimetal of zirconium and lanthanum (Zr-La) prepared by sol-gel (SG) and
      hydrothermal (HT) methods. The catalysts were characterized by means of N2
      physisorption, SEM/EDX, and NH3-TPD. The experimental results demonstrated that
      the Zr-La/SBA-15-HT exhibited the highest catalytic activity. Ethanol conversion
      and ethylene selectivity were found to increase with increased reaction
      temperature. The best catalytic results were achieved for Zr-La/SBA-15-HT
      indicating values of ethanol conversion and ethylene yield of ca. 84% and 80%,
      respectively at 400 degrees C. The most important parameter influencing their
      catalytic properties appears to be the interaction between metal and support
      depending on different methods. The metal dispersion inside the siliceous matrix
      of SBA-15 has a direct influence on their surface acidity. Meanwhile, the
      performance of these SBA-15 supported catalysts in ethanol dehydration is also
      related with the alteration of surface acidity caused by the introduction of Zr
      and Zr-La.

PMID- 29367489
TI  - Small Angle X-ray Scattering and Electron Spin Resonance Spectroscopy Study on
      Fragrance Infused Cationic Vesicles Modeling Scent-Releasing Fabric Softeners.
AB  - Industrially relevant systems for household and personal-care products often
      involve a large number of components. Such multiple component formulations are
      indispensable and effective for functionalization of the products, but may
      simultaneously provide more complex structural features compared to those in
      ideal systems comprising a smaller number of highly pure substances. Using
      cryogenic transmission electron microscopy (cryo-TEM), small angle X-ray
      scattering (SAXS), and electron spin resonance (ESR) spectroscopy, we have
      investigated effects of fragrance-incorporation into cationic vesicles on their
      bilayer structures and membrane-membrane interactions. Cationic vesicles were
      prepared from TEQ surfactant, whose major component was di(alkyl fatty ester)
      quaternary ammonium methosulfate, and fragrance components, l-menthol, linalool,
      and d-limonene, were infused into the vesicle membranes to model scent-releasing
      fabric softeners. The cryo-TEM images confirm formation of multilamellar vesicles
      (MLVs). Generalized indirect Fourier transformation (GIFT) analysis of the SAXS
      intensities based on the modified Caille structure factor model reveals that
      incorporation of a more hydrophobic fragrance component leads to a more
      pronounced increase of the surface separation (water layer thickness).
      Furthermore, the fragrance-infused systems show longer-range order of the bilayer
      correlations and enhanced undulation fluctuation of the membranes than those in
      the TEQ alone system. The spin-label ESR results indicate different restricted
      molecular motions in the TEQ bilayers depending on the labeled position and their
      marked changes upon addition of the fragrance components, suggesting different
      mixing schemes and solubilization positions of the fragrance molecules in the TEQ
      bilayers. The present data have demonstrated how the infused fragrance molecules
      having different hydrophobicity and molecular architectures into the cationic
      vesicles affect the membrane structures and the intermembrane interactions, which
      may provide useful information for precisely controlling a fragrance-releasing
      property.

PMID- 29367490
TI  - Aggregation and pH Responsive Behavior of Thioester Surfactants and Formation of
      Disulfide Linkages in Aqueous Solutions.
AB  - pH responsive surfactants, [C12H25N(CH3)2(CH2)nSCOCH3]Br (C12nSAc, n = 4, 11,
      12), were prepared, and their properties in aqueous solution were examined. The
      critical micelle concentration (cmc) and critical vesicle concentration (cvc)
      were determined based on changes in conductivity, as well as by fluorescence
      measurements, and light scattering methods. A significant increase in the light
      scattering intensities of the C12nSAc (n=11, 12) systems suggested that the
      growth of aggregates was accompanied by considerable counterion binding with
      increasing surfactant concentration. The diameter of C1211SAc, recorded by the
      dynamic light scattering measurements, was about 9.6 +/-1.0 nm, which was
      slightly smaller than that for didodecyldimethylammonium bromide (DDAB) vesicles.
      The thioester group was easily hydrolyzed upon the addition of NaOH, while it was
      hardly hydrolyzed with the addition of HCl. The time course of alkaline
      hydrolysis was examined by the conductivity measurements and high-performance
      liquid chromatography analysis. [C12H25N(CH3)2(CH2)11SS(CH2)11N(CH3)2C12H25]2Br
      (2C1211SS) was generated in the C1211SAc alkaline solution because of air
      oxidation. The C1211SAc alkaline solution gradually became an opaque blue color
      with increasing light scattering at 346 nm, indicating the remarkable growth of
      vesicles. The chemical structure of 2C1211SS was consistent with that of a
      disulfide linked double tailed surfactant, similar to DDAB. The disulfide linkage
      between the double tailed surfactants will contribute to the stabilization and
      growth of vesicles.

PMID- 29367491
TI  - Inhibitory effect of Lactococcus lactis on the bioactivity of
      periodontopathogens.
AB  - Lactococcus lactis is a probiotic bacterium that produces various bacteriocins.
      Periodontopathogens induce inflammation and halitosis through the actions of
      lipopolysaccharide (LPS) and trypsin-like enzymes. The purpose of this study was
      to investigate the inhibitory effects of L. lactis on the bioactivity of
      periodontopathogens. To investigate the antimicrobial peptide of L. lactis, the
      spent culture medium (SCM) of L. lactis was treated with or without proteinase K
      after collection by centrifugation, and the antibacterial activity of SCM against
      periodontopathogens was assessed. To evaluate the neutralizing effect of L.
      lactis on halitosis, SCM of periodontopathogens was mixed with an L. lactis
      suspension, and the levels of volatile sulfur compounds (VSCs) were measured by
      gas chromatography. LPS from the periodontopathogens was extracted by an LPS
      extraction kit with little modification, and THP-1 cells as a monocytic cell line
      were treated with the extracted LPS in the presence or absence of UV-killed L.
      lactis. The production of inflammatory cytokines was analyzed by ELISA. The SCM
      of L. lactis exhibited antimicrobial activity against the periodontopathogens,
      whereas the proteinase K-treated SCM showed little antimicrobial activity. In
      addition, the L. lactis suspension had a neutralizing effect on the VSCs produced
      by periodontopathogens, and UV-killed L. lactis inhibited the production of IL-6
      and TNF-alpha induced by the LPS. These results suggest that L. lactis may be a
      useful probiotic to prevent and treat periodontitis and halitosis.

PMID- 29367493
TI  - Substrate specificity of Nudix hydrolases from Myxococcus xanthus.

PMID- 29367492
TI  - Mumiamicin: Structure and bioactivity of a new furan fatty acid from Mumia sp.
      YSP-2-79.
AB  - A new antibiotic, designated mumiamicin, was isolated from the cultured broth of
      the rare actinomycete strain, Mumia sp. YSP-2-79, by Diaion HP-20, silica gel and
      ODS column chromatography, followed by HPLC purification. The chemical structure
      of mumiamicin was elucidated as a new furan fatty acid by nuclear magnetic
      resonance and mass spectrometry. Mumiamicin showed antimicrobial activity and
      antioxidative activity.

PMID- 29367494
TI  - [Amendment Ordinance on Safety and Health of Work under High Pressure and
      Occupational Health].

PMID- 29367496
TI  - Lingual ganglioneuroma in a dog.
AB  - A mass was found at the base of the dorsum linguae of a male 11-year-old Labrador
      retriever. The tumor comprised of ganglion cells and Schwannian cells with
      Verocay bodies. The ganglion cells were positive for neuron-specific enolase, S
      100, nerve growth factor receptor, and beta III tubulin. The Schwannian cells
      were positive for neuron-specific enolase, S-100, nerve growth factor receptor,
      and glial fibrillary acidic protein. The lingual mass was diagnosed as a
      ganglioneuroma. To our knowledge, there has been no previous report of a lingual
      ganglioneuroma in a dog.

PMID- 29367495
TI  - Late pregnancy is vulnerable period for exposure to BPA.
AB  - Bisphenol A (BPA) is among the better-known endocrine disruptors. BPA is used in
      various food-contacting materials and is easily eluted into food; as a result, we
      are exposed to BPA on a daily basis. In adults, BPA is metabolized and eliminated
      rapidly from the body. However, numerous reports suggest that fetuses and young
      children are susceptible to BPA. One of the concerning adverse effects of BPA is
      disruption of behavior, especially anxiety-like behavior. In order to study the
      mechanism of influences on offspring, it is important to clarify the most
      vulnerable gestation period. We hypothesized that offspring in late pregnancy
      would be more susceptible to BPA, because late pregnancy is a critical time for
      functional brain development. In this study, C57BL/6 mouse fetuses were exposed
      prenatally by oral dosing of pregnant dams, once daily from gestational day 5.5
      to 12.5 (early pregnancy) or 11.5 to 18.5 (late pregnancy), with BPA (0 or 10
      mg/kg body weight). Following birth and weaning, the resulting pups were tested
      using an elevated plus maze at postnatal week 10. The behavior of the offspring
      was altered by prenatal BPA exposure during late pregnancy but not during early
      pregnancy. These results indicated that offspring are more vulnerable to exposure
      to BPA in late pregnancy.

PMID- 29367497
TI  - Registry Assessment of Peripheral Interventional Devices (RAPID) - Registry
      Assessment of Peripheral Interventional Devices Core Data Elements.
AB  - BACKGROUND: The current state of evaluating patients with peripheral artery
      disease and more specifically of evaluating medical devices used for peripheral
      vascular intervention (PVI) remains challenging because of the heterogeneity of
      the disease process, the multiple physician specialties that perform PVI, the
      multitude of devices available to treat peripheral artery disease, and the lack
      of consensus about the best treatment approaches. Because PVI core data elements
      are not standardized across clinical care, clinical trials, and registries,
      aggregation of data across different data sources and physician specialties is
      currently not feasible.Methods and Results:Under the auspices of the U.S. Food
      and Drug Administration's Medical Device Epidemiology Network initiative-and its
      PASSION (Predictable and Sustainable Implementation of the National Registries)
      program, in conjunction with other efforts to align clinical data standards-the
      Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was
      convened. RAPID is a collaborative, multidisciplinary effort to develop a
      consensus lexicon and to promote interoperability across clinical care, clinical
      trials, and national and international registries of PVI. The current manuscript
      presents the initial work from RAPID to standardize clinical data elements and
      definitions, to establish a framework within electronic health records and health
      information technology procedural reporting systems, and to implement an
      informatics-based approach to promote the conduct of pragmatic clinical trials
      and registry efforts in PVI. CONCLUSIONS: Ultimately, we hope this work will
      facilitate and improve device evaluation and surveillance for patients,
      clinicians, health outcomes researchers, industry, policymakers, and regulators.

PMID- 29367500
TI  - Mucoepidermoid Carcinoma of Arising from a Bronchogenic Cyst of the Diaphragm.
AB  - INTRODUCTION: Bronchogenic cysts may rupture or become infected, and malignant
      degeneration may occur. Although various types of malignant degeneration have
      been described, only a few reports of mucoepidermoid carcinoma arising from a
      bronchogenic cyst have been published. We report such a case. CASE: A 77-year-old
      female was referred to our institution for evaluation of left chest pain. A
      computed tomography scan showed an enhancing 65 * 70 mm mass of the left
      diaphragm. Based on the intraoperative findings of an intradiaphragmatic tumor
      involving the lower lobe of the left lung, the resection of the tumor with the
      wedge resection of left lower lobe and partial resection of the left diaphragm
      was performed. Histopathologic examination revealed a mucoepidermoid carcinoma
      arising from a bronchogenic cyst of the diaphragm with the presence of fibrous
      adhesion to the lower lobe. CONCLUSION: We believe that complete resection of any
      bronchogenic cyst is justified.

PMID- 29367501
TI  - Is Pleurectomy/Decortication Superior to Extrapleural Pneumonectomy for Patients
      with Malignant Pleural Mesothelioma? A Single-Institutional Experience.
AB  - PURPOSE: This study was performed to compare the outcome of
      pleurectomy/decortication (P/D) with that of extrapleural pneumonectomy (EPP) for
      patients with malignant pleural mesothelioma (MPM). METHODS: Patients with MPM
      underwent either P/D or EPP from August 2008 to December 2014. Various
      clinicopathological factors were analyzed to identify differences between the two
      procedures. RESULTS: P/D was performed in nine patients and EPP in 30 patients.
      Most of the patients' background characteristics were not significantly different
      between the groups. The surgery time (680 vs. 586 min, p = 0.0034) and bleeding
      volume (4050 vs. 2110 mL, p = 0.002) were significantly greater in P/D than in
      EPP; however, grade >=3 complications (44% vs. 33%, p = 0.54) and length of
      postoperative hospital stay (29 vs. 37 days, p = 0.26) were not significantly
      different. The median survival time and 2- and 3-year survival rates in all
      patients were 16.7 months, 28.5%, and 15.3%, respectively. The median survival
      time and 2- and 3-year survival in the P/D and EPP groups were 22.5 months,
      43.8%, and 43.8% and 16.5 months, 24.0%, and 14.4%, respectively (p = 0.13).
      CONCLUSION: Survival of patients with MPM remains poor despite multidisciplinary
      treatment. P/D is comparable with EPP and could be a safe and another surgical
      treatment for patients with MPM.

PMID- 29367502
TI  - [CHYLOUS LEAKAGE AFTER LAPAROSCOPIC RENAL AND ADRENAL SURGERY].
AB  - (Objectives) It is recognized that Chylous leakage is a rare complication but is
      a relevant clinical problem after major abdominal surgery. It was occasionally
      reported in urologic surgery, but the data about its incidence and treatment
      outcome is still lacking. In this study, we reviewed our cases of chylous leakage
      after laparoscopic adrenalectomy or nephrectomy. (Patients and methods) From
      January 2005 to September 2014, laparoscopic adrenalectomies or nephrectomies
      were performed in 300 patients. The factors that affected the development of
      chylous leakage were analyzed. (Results) The overall incidence of chylous leakage
      was 4.3% (13 of 300 cases). All chylous leakage was seen on the left side, and it
      was commonly developed in patients with lymph node dissection or excessive hilar
      dissection around the left renal pedicle. Importantly, all cases were
      successfully managed conservatively by a low fat diet with or without octreotide.
      (Conclusions) Our results suggest that chylous leakage is not a rare complication
      after laparoscopic adrenalectomy or nephrectomy, but most cases can be treated
      conservatively. Chylous leakage can occur in patients with lymphadenectomy or
      hilar dissection on the left side.

PMID- 29367503
TI  - [ROBOT-ASSISTED RADICAL PROSTATECTOMY FOR MEN AGE 75 AND OLDER].
AB  - (Objectives) Surgical treatment prostate cancer in elderly patients is
      controversial. However, robot-assisted radical prostatectomy (RARP) is a less
      invasive procedure than conventional surgery. Therefore, we perform RARP for
      elderly patients whose general condition is good (Performance status <=1). The
      aim of this study is to evaluate surgical, oncological and functional outcomes
      for RARP in men age 75 and older. (Patients and methods) From July 2013 to April
      2016, 300 patients underwent RARP at our institution. They were divided into two
      groups: an older patient group (>=75 years) and a younger patient group (<75
      years). Treatment outcomes for each group, including surgical, oncological and
      functional outcomes, were compared. (Results) There were no statistically
      significant differences in surgical outcomes with the exception of nerve sparing
      rates (older patients: 5.9% vs. younger patients: 17.7%, P=0.0192). Importantly,
      intra- and postoperative complication rates were similar in both groups (minor
      complication: 7.4% vs. 3.9%, P=0.322, major complication: 0.0% vs. 2.2%,
      P=0.592). Regarding oncological outcomes, including positive surgical margin rate
      and PSA failure (PSA>0.2 ng/ml) at 12 months after surgery, no significant
      differences existed. Lastly, functional outcomes between the groups, including
      continence (<=1 pads/day) at 12 months after surgery, had no significant
      differences. (Conclusions) Our data suggests that RARP can be performed safely
      for men age 75 and older, and can become a good option for older patients with
      prostate cancer.

PMID- 29367504
TI  - [SAFETY AND EFFICACY OF CONTINUOUS ADMINISTRATION OF ANTITHROMBOTIC DRUGS DURING
      TRANSURETHRAL RESECTION OF BLADDER TUMORS].
AB  - (Objectives) We evaluated the safety and efficacy of continuous administration of
      antithrombotic drugs during transurethral resection of bladder tumors (TURBT).
      (Methods) We performed a retrospective review of 351 TURBT procedures performed
      at our institute from April 2011 to October 2015. Among these, antithrombotic
      drugs were continued in 31 TURBT cases throughout their perioperative period
      (continuation group), antithrombotic drugs were discontinued in 26 TURBT cases
      (discontinuation group), and bridging anticoagulation therapy with heparin after
      interruption of antithrombotic drugs was performed in 4 TURBT cases (heparin
      bridging group). The safety and efficacy of continuous administration of
      antithrombotic drugs during TURBT was evaluated by comparing the rate of
      perioperative complications, median operative time, duration of hematuria,
      urethral catheter placement, duration of stay after surgery, and by comparing the
      duration of stay among the three groups. (Results) The median operative time was
      40.0 min in the continuation group, 39.0 min in the discontinuation group, and
      31.0 min in the heparin bridging group with no significant differences. There
      were no significant differences in the median duration of hematuria (1.00 days
      vs. 1.00 days vs. 1.00 days), urethral catheter placement (3.00 days vs. 2.50
      days vs. 2.00 days), or stay after TURBT (4.00 days vs. 3.50 days vs. 3.00 days)
      among the continuation, discontinuation, and heparin bridging groups. The median
      duration of stay was 6.00 days in the continuation group, 7.00 days in the
      discontinuation group, and 16.0 days in the heparin bridging group with
      significant differences between the continuation group vs. the heparin bridging
      group and the discontinuation group vs. the heparin bridging group. The rate of
      complications was 6 (19.4%) in the continuation group and 3 (11.5%) in the
      discontinuation group with no significant differences. However, a serious
      complication, cerebral infarction leading to hemiplegia, occurred in the
      discontinuation group. (Conclusion) Continuous administration of antithrombotic
      drugs during TURBT is considered to be safe and useful because it may prevent
      serious thromboembolism without adversely affecting the perioperative course.

PMID- 29367505
TI  - [CORRESPONDENCE OF POLYMICROBIAL BACTERIURIA IN THE UNCOMPLICATED URINARY TRACT
      INFECTION OF THE PREMENOPAUSAL WOMAN].
AB  - (Objectives) We report the clinical features about polymicrobial bacteria
      detection cases in the uncomplicated urinary tract infection of the premenopausal
      woman from the voided midstream urine culture. (Methods) We retrospectively
      reviewed the premenopausal woman from 18-49 years patients visited Sendai City
      Hospital from April, 2006 to December, 2014, diagnosed uncomplicated cystitis or
      uncomplicated pyelonephritis. We analyzed for 375 specimens from the voided
      midstream urine culture. (Results) Among 375 specimens, the urine culture
      positive for uropathogens were 211 specimens. The monomicrobial bacterial were
      detected in 184 specimens (87.2%) and polymicrobial bacterial specimens were 27
      specimens (12.8%). The most combination group was the caused bacteria and
      periurethral microorganisms in 20 specimens (74.1%). Then 6 periurethral
      microorganisms specimens (22.2%), the caused bacteria were only 1 specimen was
      overlapped (3.7%). The case of urinary tract infections recurrence or revealed
      voiding dysfunction that need periodic treatment were more prevalent in the
      polymicrobial than the monomicrobial group (22.2% vs 9.8%, p=0.043).
      (Conclusions) When polymicrobial bacteria were detected in uncomplicated urinary
      tract infection in premenopausal woman, it was confirmed that there were the most
      combinations of caused bacteria and periurethral microorganisms. In these cases,
      treatment intended for only the caused bacteria. A risk of the infection
      recurrence and voiding dysfunction were statistically significant higher rate in
      the polymicrobial bacteria detection cases, and it might be necessary to consider
      that search to complicated urinary tract infection.

PMID- 29367506
TI  - [LAPAROSCOPIC LYMPHADENECTOMY FOR POSTOPERATIVE LYMPH-NODE METASTASIS OF RENAL
      MUCINOUS TUBULAR AND SPINDLE CELL CARCINOMA: A CASE REPORT].
AB  - We describe renal mucinous tubular and spindle cell carcinoma (MTSCC) that
      metastasized to the lymph nodes seven years after radical nephrectomy. An 80-year
      old man was admitted for treatment of a right renal tumor. A 6.5*6.0-cm tumor in
      the right kidney (cT1bN0M0) revealed by abdominal computed tomography was treated
      by laparoscopic radical nephrectomy. The pathological findings at that time
      suggested papillary renal cell carcinoma type 1. Imaging findings seven years
      later revealed enlarged pre-caval and right external iliac lymph nodes indicative
      of delayed metastasis, and these were treated by laparoscopic lymphadenectomy.
      The pathological findings and re-evaluation of the primary tumor suggested MTSCC.
      The patient remains free of metastasis at 24 months of follow-up. MTSCC has been
      a distinct entity in the World Health Organization classification of kidney
      tumors since 2004. Tumors consist of tubules and cords separated by pale mucinous
      material in some areas, whereas others have dense cellularity without significant
      mucin. They are usually of low malignant potential, and metastasis has rarely
      been reported. To our knowledge, this is the first report of MTSCC with
      retroperitoneal lymph node metastasis treated by lymphadenectomy.

PMID- 29367507
TI  - [A CASE OF METASTATIC BLADDER UROTHELIAL CARCINOMA WHOSE DISEASE WAS CONTROLLED
      FOR A RELATIVE LONG PERIOD BY MULTIDISCIPLINARY TREATMENT INCLUDING RADIATION TO
      A LUNG METASTASIS AND MULTIPLE COURSES OF CHEMOTHERAPY].
AB  - A 67-year-old woman complained of urinary frequency and gross hematuria. She was
      referred to our hospital with the diagnosis of bladder tumor. Transurethral
      resection of the bladder tumor (TURBT) was performed and pathological diagnosis
      was urothelial carcinoma (G2>G3) with muscular invasion. Because she hoped
      bladder preservation therapy, she received two courses of M-VAC (methotrexate,
      vinblastine, doxorubicin and cisplatin) therapy, one course of arterial infusion
      chemotherapy, and chemoradiotherapy with cisplatin. After those therapies she
      underwent 4 times of TURBT and two courses intravesical BCG therapy. However,
      solitary lung metastasis appeared 19 months after the initial TURBT.
      Multidisciplinary treatments including 25 courses of various multiagent
      chemotherapies, radiation therapy to the lung metastasis and surgical resection
      of a urethral recurrence were performed. Although a localized radiation
      pneumonitis was developed, the lung metastasis appeared to be controlled for 26
      months after the radiation therapy to the lung. Bilateral ureteral and renal
      pelvic tumors appeared after the radiation therapy. Severe bleeding was occurred
      from renal pelvic tumors several times and she needed the hospital stay 2 times.
      Active bleeding stopped after the administration of chemotherapy each time.
      Although she died of occlusive jaundice due to the liver metastasis, she had been
      alive due to the multidisciplinary treatment for 67 months after lung metastasis
      appearance with relatively good performance status.

PMID- 29367508
TI  - [CUTANEOUS METASTASIS OF UROTHERIAL CARCINOMA FOR WHICH MOHS PASTE WAS USEFUL: A
      CASE REPORT].
AB  - The patient was a 71-year-old man referred to our department because of
      asymptomatic gross hematuria. Detailed examination led to a diagnosis of
      bilateral ureteral cancer and prostate cancer. Total nephroureterectomy was
      performed for bilateral ureteral cancers on separate occasions, while prostate
      cancer was managed with hormone therapy. Because multiple bladder tumors were
      found by cystoscopy conducted after 3 months, total cystectomy was performed.
      Neither distant metastasis nor local recurrence had developed, 2 years later,
      when the patient visited our department again because of glans enlargement and
      received a diagnosis of penile cancer. Partial penectomy was performed, and a 1
      cm indurated nodule was found in the skin of the hypogastric region during
      surgery and treated by simultaneous wedge-shaped excision. Histopathologically,
      the lesions were urothelial carcinomas. Multiple metastatic foci occurred in the
      skin postoperatively centering on the hypogastric region, growing rapidly and
      accompanied by bleeding and exudate causing a bad odor. Topical application of
      Mohs paste resulted in dramatic improvement of the pain and exudate, which
      thereby improved the patient's quality of life (QOL) to a level enabling
      discontinuation of narcotic drug therapy for cancer-related pain. Thereafter,
      hepatic metastasis was found and chemotherapy with gemcitabine and paclitaxel was
      administered. The patient did not respond to this chemotherapy and died of cancer
      3 months later. Cutaneous metastasis of urothelial carcinoma, which is a very
      rare condition, is often managed with palliative therapy due to the lack of
      response to anticancer chemotherapy. In such cases, the use of Mohs paste appears
      to be of great value for maintaining the patient's QOL which otherwise might
      deteriorate markedly.

PMID- 29367509
TI  - [FEMALE PARAURETHRAL LEIOMYOSARCOMA: A CASE REPORT].
AB  - A 54-year-old woman visited another hospital with complaining of a palpable mass
      in vagina and dysuria. The mass had gradually enlarged since the past 2 years.
      Ultrasonography and CT revealed the tumor located between the urethra and vaginal
      mucosa. Histopathological examination was well-differentiated leiomyosarcoma from
      transvaginal needle biopsy. She was referred to our hospital. On MRI, the 4-cm
      tumor showed no infiltration into the vaginal mucosa or urethra. PET/CT showed a
      high uptake of FDG. No metastatic disease was evident. We performed excision of
      the tumor transvaginally. The tumor cells demonstrated immunoreactivity for
      estrogen receptors and partially progesterone receptors in histopathological
      examination. We speculated that the developmental mechanism of female
      paraurethral leiomyosarcoma was associated with female leiomyosarcoma in other
      surrounding pelvic organs.

PMID- 29367510
TI  - [A CASE OF DEXTRANOMER-HYALURONIC ACID COPOLYMER (Deflux(r)) IMPLANTS
      CALCIFICATION MIMICKING DISTAL URETERAL CALCULI].
AB  - Since 2011, endoscopic correction of vesicoureteral reflux using dextranomer
      hyaluronic acid copolymer (Deflux(r)) has been widely accepted in Japan due to
      its safety and minimally invasive nature. However, long-term complications are
      unknown. We present a case of Deflux(r) implants calcification mimicking distal
      ureteral calculi in a 12-year-old boy with a history of Deflux(r) injection
      performed at three years of age for primary VUR. We should be aware of this
      complication to avoid misdiagnosis and unnecessary invasive examination such as
      radiological imaging or endoscopy.

PMID- 29367511
TI  - [SIGNIFICANCE OF INTRADUCTAL CARCINOMA OF THE PROSTATE IN POST-OPERATIVE
      BIOCHEMICAL RECURRENCE].
AB  - (Objective) We investigated the prognostic significance of intraductal carcinoma
      of the prostate (IDC-P) in radical prostatectomy specimens. (Materials and
      methods) We evaluated 441 patients treated with radical prostatectomy and
      analyzed data on IDC-P, lymph node metastases, Gleason score, seminal vesicle
      invasion, extraprostatic extension, surgical margin, total cancer volume, and
      zonal origin of dominant cancer focus in radical prostatectomy specimens. The
      median follow-up was 50 months (range 6-164 months). (Results) We identified IDC
      P in 112 cases (25.4%). The five-year biochemical progression-free survival rate
      in patients with IDC-P was significantly lower than for those without IDC-P
      (35.8% vs 69.6%; p<0.0001). In a univariate analysis, IDC-P (p<0.0001), lymph
      node metastases (p=0.0022), Gleason score (p<0.0001), seminal vesicle invasion
      (p<0.0001), extraprostatic extension (p<0.0001), surgical margin (p<0.0001) and
      total cancer volume (p<0.0001) were significantly associated with the biochemical
      progression-free survival. In a multivariate analysis, Gleason score (p<0.0001),
      IDC-P (p=0.0002), seminal vesicle invasion (p=0.0011), extraprostatic extension
      (p=0.0012), surgical margin (p=0.0019) and lymph node metastases (p=0.0402) were
      significantly associated with biochemical progression-free survival.
      (Conclusions) The presence of IDC-P is an independent factor of biochemical
      recurrence in prostate cancer patients treated with radical prostatectomy. We
      therefore recommend that the presence of IDC-P in radical prostatectomy specimens
      be reported.

PMID- 29367512
TI  - [A CASE OF PELVIC FRACTURE URETHRAL INJURY RECONSTRUCTED BY DEFERRED
      URETHROPLASTY].
AB  - We report a case of pelvic fracture urethral injury reconstructed by anastomotic
      urethroplasty. A 24-year-old male was referred to our hospital because of pelvic
      trauma accompanying ischial fracture. Retrograde urethrography showed urethral
      disruption and suprapubic catheter was inserted. One week later, we underwent
      endoscopic realignment. Three months later, we removed the Foley balloon catheter
      after we had checked that there was no stricture by the voiding cystourethrogram.
      However, 5 days after that, he came to our hospital because of urinary retention.
      Cystoscopy detected urinary stricture between bulbar and membranous urethra. We
      decided to do deferred urethroplasty. Five months after that we performed
      anastomotic urethroplasty. He was discharged 31 days after the operation. No
      stricture has been detected for 7 months postoperatively.

PMID- 29367513
TI  - Gadolinium-based Contrast Media, Cerebrospinal Fluid and the Glymphatic System:
      Possible Mechanisms for the Deposition of Gadolinium in the Brain.
AB  - After Kanda's first report in 2014 on gadolinium (Gd) deposition in brain tissue,
      a considerable number of studies have investigated the explanation for the
      observation. Gd deposition in brain tissue after repeated administration of
      gadolinium-based contrast medium (GBCM) has been histologically proven, and
      chelate stability has been shown to affect the deposition. However, the mechanism
      for this deposition has not been fully elucidated. Recently, a hypothesis was
      introduced that involves the 'glymphatic system', which is a coined word that
      combines 'gl' for glia cell and 'lymphatic' system. According to this hypothesis,
      the perivascular space functions as a conduit for cerebrospinal fluid to flow
      into the brain parenchyma. The perivascular space around the arteries allows
      cerebrospinal fluid to enter the interstitial space of the brain tissue through
      water channels controlled by aquaporin 4. The cerebrospinal fluid entering the
      interstitial space clears waste proteins from the tissue. It then flows into the
      perivascular space around the vein and is discharged outside the brain. In
      addition to the hypothesis regarding the glymphatic system, some reports have
      described that after GBCM administration, some of the GBCM distributes through
      systemic blood circulation and remains in other compartments including the
      cerebrospinal fluid. It is thought that the GBCM distributed into the
      cerebrospinal fluid cavity via the glymphatic system may remain in brain tissue
      for a longer duration compared to the GBCM in systemic circulation. Glymphatic
      system may of course act as a clearance system for GBCM from brain tissue. Based
      on these findings, the mechanism for Gd deposition in the brain will be discussed
      in this review. The authors speculate that the glymphatic system may be the major
      contributory factor to the deposition and clearance of gadolinium in brain
      tissue.

PMID- 29367514
TI  - Intravascular Ultrasound-Derived Virtual Fractional Flow Reserve for the
      Assessment of Myocardial Ischemia.
AB  - BACKGROUND: Fractional flow reserve (FFR) is widely used for the assessment of
      myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging
      method that provides information about lumen and vessel morphology. Previous
      studies on the expanded use of IVUS to identify functional ischemia have noted an
      association between anatomy and physiology, but IVUS-derived minimum lumen area
      (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR.
      We developed a method to calculate FFR using IVUS-derived anatomical information
      for the assessment of myocardial ischemia. The aims of this study were to
      investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS
      FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for
      functional assessment.Methods and Results:We retrospectively analyzed 50 lesions
      in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously.
      IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean
      percent diameter stenosis determined on quantitative coronary angiography and on
      FFR was 56.4+/-10.7 and 0.69+/-0.08, respectively. IVUS-FFR had a stronger linear
      correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units)
      than with IVUS-derived MLA (R=0.43, P=0.002). CONCLUSIONS: IVUS-FFR may be a more
      valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

PMID- 29367515
TI  - Do Patients With High CHA2DS2-VASc Scores Need High Intensity of Anticoagulants
      After Valve Surgery?
AB  - BACKGROUND: Asian patients on warfarin therapy usually have lower international
      normalized ratio (INR) intensities than those recommended by Western clinical
      practice guidelines. This study evaluated whether a high INR reduces the
      incidence of thromboembolism (TE) or bleeding events in Asian patients with high
      CHA2DS2-VASc scores after valve surgery.Methods and Results:Data of adult
      patients after valve surgery were retrieved from an integrated healthcare
      information system of a single hospital between 2014 and 2016. The INR was
      derived from the closest laboratory data before the index outpatient-clinic visit
      date. The endpoint of every record was determined as emergency room visit or
      hospitalization because of TE or bleeding event. A total of 37 TE or bleeding
      events were retrieved from 8,207 records; the annual incidence rate were 1.2% and
      2.8% for low (0-2) and high (3-8) CHA2DS2-VASc score groups, respectively
      (P=0.007). The incidence rates were lowest for both groups at an INR of 1.5-2.0.
      High INR intensities did not reduce TE or bleeding incidence. INR >3.0 was
      associated with increased TE or bleeding incidence in the high-score group
      (6.8%/year vs. 2.0%/year, P=0.079). CONCLUSIONS: The optimal INR is 1.5-2.5 for
      low- or high-score Asian patients after valve surgery. INR >3.0 was associated
      with increased TE or bleeding incidence in the high-score group.

PMID- 29367516
TI  - Isolation, identification and characterization of novel Bacillus subtilis.
AB  - In this study, we have identified a bacterium that can inhibit the growth of
      Staphylococcus aureus, and further analyzed its antibacterial activity and other
      biological characteristics and laid the foundation for its future application.
      Through isolation and culture of the unknown bacteria, the culture
      characteristics, morphology observation, biochemical test, preliminary
      antibacterial test, 16S rRNA PCR amplification, sequence analysis, and homology
      analysis were performed. It was found that the bacteria are Gram positive spore
      chain Bacillus. The bacteria could only ferment glucose for acid production, but
      could not utilize lactose and maltose. The VP test for this bacteria was
      positive, while indole and methyl red tests were negative. Further analysis
      showed that these bacteria shared a homology up to 99.4% with Bacillus subtilis
      DQ198162.1. Thus, this newly identified bacterium was classified as Bacillus
      subtilis. Importantly, the crude bacteriocin of this Bacillus subtilis could
      inhibit the growth of Staphylococcus aureus, Escherichia coli, Enterococcus and
      Salmonella, which implies its potential usage in the future.

PMID- 29367517
TI  - One-step triplex PCR/RT-PCR to detect canine distemper virus, canine parvovirus,
      and canine kobuvirus.
AB  - To rapidly distinguish Canine distemper virus (CDV), canine parvovirus (CPV), and
      canine kobuvirus (CaKoV) in practice, a one-step multiplex PCR/RT-PCR assay was
      developed, with detection limits of 102.1 TCID50 for CDV, 101.9 TCID50 for CPV
      and 103 copies for CaKoV. This method did not amplify nonspecific DNA or RNA from
      other canine viruses. Therefore, the assay provides a sensitive tool for the
      rapid clinical detection and epidemiological surveillance of CDV, CPV and CaKoV
      in dogs.

PMID- 29367518
TI  - Molecular characteristics and virulence analysis of eight Aeromonas hydrophila
      isolates obtained from diseased Amur sturgeon Acipenser schrenckii Brandt, 1869.
AB  - Aeromonas hydrophila is an opportunistic pathogen of a variety of aquatic animals
      that displays extreme diversity in drug resistance, phenotypes, virulence genes,
      and virulence. In this study, eight pathogenic A. hydrophila strains were
      isolated from diseased Amur sturgeons and investigated for their sensitivity to
      select antibiotics, their phenotype, virulence genes, and virulence. According to
      the phylogenetic analysis of the DNA gyrase subunit B protein, the eight isolates
      formed a single branch in the A. hydrophila group. The antibiotics ceftazidime,
      cefuroxime, cefoperazone, cefotaxime, ceftriaxone, aztreonam, and cefepime
      appeared effective against them. All of the isolates possessed the virulence
      genes for aerolysin, flagellin, heat-stable cytotonic enterotoxin, heat-labile
      cytotonic enterotoxin, hemolysin, and elastase, while only one isolate, HZ8,
      possessed the gene for lateral flagella. The cytolytic enterotoxin and lipase
      genes were present in all isolates, except in ZJ10 and ZJ12. Enterobacterial
      repetitive intergenic consensus sequence PCR indicated that the eight A.
      hydrophila isolates could be divided into four types. Isolates YW2, TR3, HZ8 and
      ZJ10, each representing a different type, were selected for challenge
      experiments. The challenge tests revealed that isolate HZ8 had the lowest lethal
      dose, causing 50% mortality at 2.30 * 104 colony forming units (cfu)/ml. The
      isolate ZJ10 had the highest LD50, 1.25 * 106 cfu/ml. Knowledge of the
      characteristics of the A. hydrophila isolates obtained from Amur sturgeon will be
      beneficial in developing potential disease control strategies.

PMID- 29367519
TI  - Restraint stress in lactating mice alters the levels of sulfur-containing amino
      acids in milk.
AB  - It is well known that maternal stress during the gestation and lactation periods
      induces abnormal behavior in the offspring and causes a lowering of the
      offspring's body weight. Various causes of maternal stress during the lactation
      period, relating to, for example, maternal nutritional status and reduced
      maternal care, have been considered. However, little is known about the effects
      on milk of maternal stress during the lactation period. The current study aimed
      to determine whether free amino acids, with special reference to sulfur
      containing amino acids in milk, are altered by restraint stress in lactating
      mice. The dams in the stress group were restrained for 30 min at postnatal days
      2, 4, 6, 8, 10 and 12. Restraint stress caused a reduction in the body weight of
      lactating mice. The concentration of taurine and cystathionine in milk was
      significantly higher in the stress group, though stress did not alter their
      concentration in maternal plasma. The ratio of taurine concentration in milk to
      its concentration in maternal plasma was significantly higher in the stress
      group, suggesting that stress promoted taurine transportation into milk.
      Furthermore, taurine concentration in milk was positively correlated with
      corticosterone levels in plasma. In conclusion, restraint stress in lactating
      mice caused the changes in the metabolism and in the transportation of sulfur
      containing amino acids and resulted in higher taurine concentration in milk.
      Taurine concentration in milk could also be a good parameter for determining
      stress status in dams.

PMID- 29367520
TI  - Cost-Effectiveness of Statin Plus Eicosapentaenoic Acid Combination Therapy for
      Cardiovascular Disease Prevention in Japanese Patients With Hypercholesterolemia 
      An Analysis Based on the Japan Eicosapentaenoic Acid Lipid Intervention Study
      (JELIS).
AB  - BACKGROUND: The addition of eicosapentaenoic acid (EPA) to statin therapy has
      been shown to reduce cardiovascular events. This study examined the cost
      effectiveness of EPA plus statin (EPA+statin) combination therapy compared with
      statin monotherapy for primary and secondary prevention of cardiovascular disease
      (CVD) in Japan.Methods and Results:A Markov model was applied to assess the costs
      and benefits associated with EPA+statin combination therapy over a projected 30
      year period from the perspective of a public healthcare funder in Japan. The
      incremental cost-effectiveness ratio (ICER), expressed as quality-adjusted life
      years (QALY), was estimated for primary prevention and secondary prevention of
      CVD in patients with hypercholesterolemia. Impact on survival and number of
      events were based on the Japan EPA Lipid Intervention Study. Sensitivity analyses
      examined the influence of various input parameters on costs and outcomes of
      treatment. ICER was Y29.6 million per QALY gained in primary prevention and Y5.5
      million per QALY gained in secondary prevention. The probabilities that
      EPA+statin combination therapy would be cost-effective compared with statin
      monotherapy were 39% in primary prevention and 49% in secondary prevention at a
      cost-effectiveness threshold of Y5 million per QALY gained. Sensitivity analyses
      showed that EPA was cost-effective in secondary prevention. CONCLUSIONS:
      EPA+statin combination therapy showed acceptable cost-effectiveness for secondary
      prevention, but not primary prevention, of CVD in patients with
      hypercholesterolemia in Japan.

PMID- 29367522
TI  - Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral
      Artery Disease.
AB  - AIM: Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with
      beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering,
      anti-inflammatory and anti-oxidant properties, it may play a protective role
      against atherosclerosis. However, blood FGF-21 levels in coronary artery disease
      (CAD) or peripheral artery disease (PAD) have not been elucidated. METHODS: We
      measured plasma FGF-21 levels in 417 patients undergoing coronary angiography,
      who also had ankle-brachial index test for PAD screening. RESULTS: CAD was found
      in 224 patients (1-vessel [1-VD], n=92; 2-vessel [2-VD], n=65; 3-vessel disease
      [3-VD], n=67). No significant difference was found in the FGF-21 levels between
      224 patients with CAD and 193 without CAD (median 26.0 vs. 25.9 pg/mL). FGF-21
      levels in 4 groups of CAD(-), 1-VD, 2-VD, and 3-VD were 25.9, 37.2, 19.4, and 0.0
      pg/mL. FGF-21 tended to be highest in 1-VD and lowest in 3-VD, but the difference
      did not reach statistical significance. PAD was found in 38 patients. Compared to
      the 379 patients without PAD, 38 with PAD had CAD more often (87% vs. 50%),
      especially 3-VD (P<0.001). FGF-21 levels were lower in patients with PAD than in
      those without PAD (0.0 vs. 30.7 pg/mL, P<0.02). In multivariate analysis, the FGF
      21 level was an independent factor for PAD, but not for CAD. Odds ratio for PAD
      was 2.13 (95%CI=1.01-4.49) for a low FGF-21 level (<15.6 pg/mL). CONCLUSION: No
      significant difference was found in the FGF-21 levels between patients with and
      without CAD. However, FGF-21 levels were low in patients with PAD, and were a
      factor for PAD independent of atherosclerotic risk factors.

PMID- 29367521
TI  - Clinical Outcomes after Isolated Infrapopliteal Revascularization in Hemodialysis
      Patients with Critical Limb Ischemia: Endovascular Therapy versus Bypass Surgery.
AB  - AIM: To investigate the long-term clinical outcome of endovascular therapy (EVT)
      or bypass surgery in patients on hemodialysis (HD) with critical limb ischemia
      due to isolated infrapopliteal disease. METHODS: We enrolled 254 consecutive HD
      patients successfully undergoing infrapopliteal revascularization by EVT (126
      patients) and bypass surgery (128 patients). They were followed up for five
      years. Amputation-free survival (AFS) and incidence of any re-intervention were
      evaluated. A propensity score from all baseline variables was incorporated into
      Cox analysis. RESULTS: In the EVT group, age was higher (p=0.039), diabetes and
      coronary artery disease were more frequent (p=0.004 and p=0.0052, respectively),
      and tissue loss was more rarely observed (p< 0.0001) than in the bypass group.
      During the follow-up period, 21 major amputations and 64 deaths occurred. The
      propensity score-adjusted AFS rate at 5 years was comparable between groups
      (61.0% in EVT group vs. 55.1% in the bypass group, adjusted hazard ratio [HR]
      0.87, 95% confidence interval [CI] 0.52-1.42, p=0.58). The adjusted survival
      rates were also similar between groups for amputation and all-cause mortality.
      However, freedom from any re-intervention was markedly lower in the EVT than in
      the bypass group (48.6% vs. 84.6%, adjusted-HR, 3.56, 95% CI 1.95-6.75, p<
      0.0001). CONCLUSIONS: The rate of AFS was broadly comparable between the two
      strategies, although compared with bypass surgery, EVT had much higher rates for
      re-intervention.

PMID- 29367523
TI  - [The pathogenic role of ACPA in rheumatoid arthritis].
AB  - In rheumatoid arthritis (RA), ACPA (anti-citrullinated protein/peptide
      antibody) is elevated with high specificity, and clinically, anti-CCP (cyclic
      citrullinated peptide) antibody is widely used for diagnosis of RA. It is thought
      ACPAs are produced with genetic background such as HLA-DR, environmental factors
      such as periodontal disease and smoking, however, the pathogenic role of ACPA in
      RA has not been elucidated. These were showed immune complexes including ACPA or
      ACPA itself promoted inflammatory cytokine production such as TNF. PADs
      (peptidylarginine deiminases) were expressed and citrullinated proteins existed
      in RA synovium. ACPAs were deposited on the site of citrulline in CD68 positive
      cells of RA synovium. The damage of bone and cartilage is observed in RA. It was
      also suggested that deposition of ACPAs caused osteoclastogenesis and bone loss.
      We introduce several findings about the pathogenic role of ACPA in RA.

PMID- 29367524
TI  - [Unmet needs in systemic lupus erythematosus].
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple
      lesions that cause inflammation and the production of autoantibodies. Lupus
      nephritis (LN) and neuropsychiatric SLE (NPSLE) are common organ-threatening
      manifestations of SLE and result in significant morbidity and mortality. In the
      last 30 years, steroids and immunosuppressive drugs have improved the prognosis
      of patients with SLE, and today the 5-year survival rate exceeds 90%. However,
      the treatment of SLE still largely depends on these medications and sometimes
      results in death due to complications. In recent years, biologic agents and low
      molecular-weight compounds have emerged that are expected to be effective against
      refractory LN and NPSLE. For the diagnosis of SLE, the classification revised in
      1997 proposed by the American College of Rheumatology and the classification
      standards of the Systemic Lupus International Collaborating Clinics 2012
      classification criteria have been used, but they are not necessarily useful for
      early diagnosis. New biomarkers are needed for the early diagnosis of SLE. In
      this article, we summarize the unmet needs of diagnosis and treatment with SLE,
      especially those with LN and NPSLE, with data from our own experiences.

PMID- 29367525
TI  - [Intestinal immune response is regulated by gut microbe].
AB  - Human Intestine has a diverse population of bacteria which induces pathogens to
      disrupt not only the intestinal homeostasis but whole body immune systems.
      Dysbiosis, the abnormal proliferation and reduction of the microbiota, breaks
      down the homeostasis of the immunity and metabolisms in the host. The evolution
      of the microbiota analysis technology contributed to reveal the molecular
      biological complex interaction between the microbiota and its host systemically
      as well as locally. Because several diseases are caused by the dysbiosis, fecal
      transplantation would be the new therapeutic target for them. It has been
      investigated in some intestinal diseases such as CD infection, or inflammatory
      bowel disease. Here, we review these symbiotic interactions and the current state
      for the clinical application.

PMID- 29367526
TI  - [The formation of skin barrier and defective barrier-associated skin diseases].
AB  - Since the discovery of loss-of-function mutations in filaggrin (FLG) gene in
      atopic dermatitis (AD) individuals, significant attention has been paid against
      the skin barrier as an initial starting point of atopic march. Although FLG is a
      significant cornification-associated gene, skin barrier formation is a complex
      process mediated by an array of genes with specific functions. In this article,
      the mechanism of physical skin barrier formation is reviewed in detail, focusing
      on specific gene functions and inherited disorders caused by genetic aberrations.
      Additionally, the mechanism of percutaneous sensitization with environmental
      allergens in association with FLG-deficiency is reviewed in order to clarify the
      link between defective skin barrier and atopic march. Finally, updated knowledge
      of psoriasis pathophysiology in connection with genetic defect in skin barrier is
      reviewed. This article would provide a novel opportunity to understand the
      allergic/autoimmune disorders from the viewpoint of non-classical immune cells.

PMID- 29367527
TI  - [The scoring system for the risk-stratification in patients with the
      antiphospholipid syndrome].
AB  - Antiphospholipid syndrome (APS) is a clinical disorder characterized by
      thrombosis and/or pregnancy morbidity in the persistence of the pathogenic
      autoantibodies, the antiphospholipid antibodies (aPL). Recurernt thrombosis is
      often observed in patients with APS which requires persistent prophylaxis.
      However, an uniform prophylactic treatment for APS patients is inadequate and
      stratification of the thrombotic risks is important as aPL are prevalently
      observed in other various diseases or elderly population. It is previously known
      that the multiple positivity or high titre of aPL correlate to the thrombotic
      events. To progress the stratification of the thrombotic risks and to
      quantitatively analyze them, antiphospholipid score (aPL-S) and the Global Anti
      Phospholipid Syndrome Score (GAPSS) were defined as the scoring-systems. Both of
      these scoring-systems were raised from the large patient cohort data and either
      aPL profile classified in detail (aPL-S) or simplified aPL profile with classical
      thrombotic risk factors (GAPSS) were put into scoring system. They have shown a
      degree of accuracy in identifying high-risk APS patients, especially those at a
      high risk of thrombosis. However, there are several areas requiring improvement,
      or at least that clinicians should be aware of, before these instruments are
      applied in clinical practice. One such issue is standardisation of the aPL tests,
      including general testing of phosphatidylserine dependent antiprothrombin
      antibodies (aPS/PT).

PMID- 29367528
TI  - [Autoimmune diseases and ubiquitin system].
AB  - Cytokines play important roles in the pathogenesis of autoimmune diseases. Anti
      TNFalpha antibody therapy for rheumatoid arthritis, Crohn's disease, and
      psoriasis has made enough progress to change its treatment goal. This review
      focuses on the recent advances that have been made in understanding TNFR
      signaling through ubiquitin system. Genome-wide association studies (GWAS)
      identified numerous susceptibility loci associated with autoimmune diseases.
      Ubiquitin related genes TNFAIP3 and TNIP1 have been linked to multiple autoimmune
      diseases. Here, we review the importance of TNFAIP3 and TNIP1-mediated regulation
      of ubiquitin-dependent signaling. To monitor the dynamics of ubiquitin chain
      formation in vivo, we have developed a polyubiquitin-mediated fluorescence
      complementation (PolyUb-FC) assay. The PolyUb-FC assay has the advantage that
      monoubiquitination is non-fluorescent and chain-specific poly-ubiquitination can
      be directly visualized in living cells without using antibodies. The PolyUb-FC
      will be a useful tool for analyzing the dynamics of polyubiquitin chain
      generation.

PMID- 29367529
TI  - [A case of anti-PL-7 antibody positive polymyositis with thrombotic
      microangiopathy].
AB  - A 65-year-old woman with a 17-year history of polymyositis and 8-year history
      of rheumatoid arthritis who was treated with a low dose of prednisolone and
      tacrolimus (Tac) was admitted to our hospital because of general malaise and
      hypertension. Blood tests showed thrombocytopenia, hemolytic anemia with
      fragmented erythrocytes, and hypercreatinemia. Based on these clinical features,
      she was diagnosed with thrombotic micro-angiopathy (TMA). Thrombocytopenia and
      hemolytic anemia with fragmented erythrocytes improved with the discontinuation
      of Tac and plasma exchange; however, hypertension and renal dysfunction
      persisted. TMA due to calcineurin inhibitor (CNI) nephropathy was suspected based
      on the histopathological findings of renal biopsy. However, the condition was
      atypical of a CNI nephropathy because the trough level of Tac was lower than that
      reported previously and renal dysfunction persisted after drug discontinuation.
      She had mild sclerodactylia and Raynaud's symptoms, although the diagnostic
      criteria for systemic sclerosis (SSc) were not satisfied. Moreover, the patient
      tested positive for anti PL-7 antibody. The relationship between anti PL-7
      antibody and pathogenesis of SSc has been reported. In this case, it was
      suspected that CNI nephropathy worsened because of the potential basic factors of
      SSc. These findings indicate that TMA may occur in patients testing positive for
      anti PL-7 antibody who are treated with Tac.

PMID- 29367530
TI  - [Transient detection of lupus anticoagulant in acute phase of Kawasaki disease].
AB  - In Kawasaki disease (KD), endothelial damage and an elevation in coagulant
      factors provoke thrombosis. Lupus anticoagulant (LA) is strongly associated with
      the risk of thrombosis in patients with antiphospholipid syndrome; however, there
      has been no report of positive LA in KD patients. A previously healthy, 2-year
      old boy was admitted due to fever, bilateral conjunctivitis, redness of the lips,
      and unilateral cervical lymphadenopathy. Typical Kawasaki disease was diagnosed
      on day 5 of illness. Adenovirus antigens were detected in his stool. After the KD
      symptoms were successfully treated with intravenous immunoglobulin, his activated
      partial thromboplastin time (APTT) increased to 88 seconds at eight days of
      illness. The cross-mixing test showed an inhibition pattern, and the presence of
      LA was proved using diluted Russell's viper venom time. APPT elongation improved
      due to continued low dose aspirin therapy without thromboembolisms. The
      possibility of contamination by LA was low because six other patients treated
      with the same immunoglobulin lot showed no APTT elongation. We speculated that KD
      related infections led to the presence of LA, which may have triggered the
      thrombosis. Further accumulation of data is warranted to elucidate the role of LA
      in KD patients.

PMID- 29367531
TI  - [A case of axial spondyloarthritis acute onset as opportunity tonsil foci
      infection].
AB  - A 49-year-old female with a chief complaints of arthralgia, and a medical
      history is Hashimoto's disease presented to us. She had been previously treated
      for Sjogren's syndrome at our hospital. She had anterior chest and polyarticular
      pain. On admission, her blood test results were as follows: white blood cells,
      12700/MUl; C reactive protein, 24.8 mg/dl; erythrocyte sedimentation rate 122
      mm/h, Anti-streptolysin O, 1179 IU/ml;an, ASK, 10240. She had tenderness in both
      her hand and finger joints, recurrent episodes of tonsillitis and pustular
      eruption. Her imaging studies were remarkable for inflammation of the sacroiliac
      joint and bone erosion of the hand joint, among other findings. We considered a
      diagnosis of either axial spondyloarthritis or synovitis acne, pustulosis,
      hyperostosis and osteitis (SAPHO) syndrome due to an opportunistic tonsillar
      infection. The differential diagnosis between axial spondyloarthritis or SAPHO
      syndrome is difficult to make. We discuss this case in the context of previous
      literature.

PMID- 29367532
TI  - [A case of mixed connective tissue disease positive for proteinase 3
      antineutrophil cytoplasmic antibody in a patient with slowly progressive type 1
      diabetes mellitus and chronic thyroiditis].
AB  - A female in her sixties with slowly progressive type 1 diabetes mellitus
      (SPT1DM) and chronic thyroiditis was referred to our rheumatology department with
      swelling in her fingers. A prominent atherosclerotic lesion was revealed upon
      brain magnetic resonance imaging, and she was found to have mixed connective
      tissue disease (MCTD) positive for proteinase 3 (PR3)-antineutrophil cytoplasmic
      antibody (ANCA). This rare case of MCTD accompanying SPT1DM and PR3-ANCA
      suggested that a synergy between MCTD and PR3-ANCA triggers atherosclerosis.

PMID- 29367534
TI  - Collagenolytic Activity Is Associated with Scar Resolution in Zebrafish Hearts
      after Cryoinjury.
AB  - Myocardial infarction is the major cause of cardiac injury in western countries
      and can result in a massive loss of heart cells, leading eventually to heart
      failure. A fibrotic collagen-rich scar may prevent ventricular wall rupture, but
      also may result in heart failure because of its stiffness. In zebrafish, cardiac
      cryoinjury triggers a fibrotic response and scarring. Unlike with mammals,
      zebrafish heart has the striking ability to regenerate and to resolve the scar.
      Thus, understanding the mechanisms of scar resolution in zebrafish heart might
      facilitate the design of new therapeutic approaches to improve the recovery of
      patients. To visualize the collagenolytic activity within the zebrafish heart
      following cryoinjury, we used an in situ collagen zymography assay. We detected
      expression of mmp2 and mmp14a and these matrix metalloproteinases might
      contribute to the collagenase activity. Collagenolytic activity was present in
      the wound area, but decreased as the myocardium regenerated. Comparison with
      neonatal mouse hearts that failed to regenerate after transmural cryoinjury
      revealed a similar collagenolytic activity in the scar. These findings suggest
      that collagenolytic activity may be key to how the zebrafish heart resolves its
      scar; however, it is not sufficient in mouse hearts that lack efficient
      myocardial regeneration.

PMID- 29367535
TI  - Management of Arrhythmias in Heart Failure.
AB  - Heart failure patients are predisposed to develop arrhythmias. Supraventricular
      arrhythmias can exacerbate the heart failure symptoms by decreasing the effective
      cardiac output and their control require pharmacological, electrical, or catheter
      based intervention. In the setting of atrial flutter or atrial fibrillation,
      anticoagulation becomes paramount to prevent systemic or cerebral embolism.
      Patients with heart failure are also prone to develop ventricular arrhythmias
      that can present a challenge to the managing clinician. The management strategy
      depends on the type of arrhythmia, the underlying structural heart disease, the
      severity of heart failure, and the range from optimization of heart failure
      therapy to catheter ablation. Patients with heart failure, irrespective of
      ejection fraction are at high risk for developing sudden cardiac death, however
      risk stratification is a clinical challenge and requires a multiparametric
      evaluation for identification of patients who should undergo implantation of a
      cardioverter defibrillator. Finally, patients with heart failure can also develop
      symptomatic bradycardia, caused by sinus node dysfunction or atrio-ventricular
      block. The treatment of bradycardia in these patients with pacing is usually
      straightforward but needs some specific issue.

PMID- 29367537
TI  - Lineages of the Cardiac Conduction System.
AB  - The cardiac conduction system (CCS) initiates and coordinately propagates the
      electrical impulse to orchestrate the heartbeat. It consists of a set of
      interconnected components with shared properties. A better understanding of the
      origin and specification of CCS lineages has allowed us to better comprehend the
      etiology of CCS disease and has provided leads for development of therapies. A
      variety of technologies and approaches have been used to investigate CCS
      lineages, which will be summarized in this review. The findings imply that there
      is not a single CCS lineage. In contrast, early cell fate decisions segregate the
      lineages of the CCS components while they remain connected to each other.

PMID- 29367536
TI  - On the Evolution of the Cardiac Pacemaker.
AB  - The rhythmic contraction of the heart is initiated and controlled by an intrinsic
      pacemaker system. Cardiac contractions commence at very early embryonic stages
      and coordination remains crucial for survival. The underlying molecular
      mechanisms of pacemaker cell development and function are still not fully
      understood. Heart form and function show high evolutionary conservation. Even in
      simple contractile cardiac tubes in primitive invertebrates, cardiac function is
      controlled by intrinsic, autonomous pacemaker cells. Understanding the
      evolutionary origin and development of cardiac pacemaker cells will help us
      outline the important pathways and factors involved. Key patterning factors, such
      as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM
      homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone
      morphogenic protein (Bmp) families are well conserved. Here we compare the
      dominant pacemaking systems in various organisms with respect to the underlying
      molecular regulation. Comparative analysis of the pathways involved in patterning
      the pacemaker domain in an evolutionary context might help us outline a common
      fundamental pacemaker cell gene programme. Special focus is given to pacemaker
      development in zebrafish, an extensively used model for vertebrate development.
      Finally, we conclude with a summary of highly conserved key factors in pacemaker
      cell development and function.

PMID- 29367538
TI  - Breast Cancer Clinical Trial of Chemotherapy and Trastuzumab: Potential Tool to
      Identify Cardiac Modifying Variants of Dilated Cardiomyopathy.
AB  - Doxorubicin and the ERBB2 targeted therapy, trastuzumab, are routinely used in
      the treatment of HER2+ breast cancer. In mouse models, doxorubicin is known to
      cause cardiomyopathy and conditional cardiac knock out of Erbb2 results in
      dilated cardiomyopathy and increased sensitivity to doxorubicin-induced cell
      death. In humans, these drugs also result in cardiac phenotypes, but severity and
      reversibility is highly variable. We examined the association of decline in left
      ventricular ejection fraction (LVEF) at 15,204 single nucleotide polymorphisms
      (SNPs) spanning 72 cardiomyopathy genes, in 800 breast cancer patients who
      received doxorubicin and trastuzumab. For 7033 common SNPs (minor allele
      frequency (MAF) > 0.01) we performed single marker linear regression. For all
      SNPs, we performed gene-based testing with SNP-set (Sequence) Kernel Association
      Tests: SKAT, SKAT-O and SKAT-common/rare under rare variant non-burden; rare
      variant optimized burden and non-burden tests; and a combination of rare and
      common variants respectively. Single marker analyses identified seven missense
      variants in OBSCN (p = 0.0045-0.0009, MAF = 0.18-0.50) and two in TTN (both p =
      0.04, MAF = 0.22). Gene-based rare variant analyses, SKAT and SKAT-O, performed
      very similarly (ILK, TCAP, DSC2, VCL, FXN, DSP and KCNQ1, p = 0.042-0.006). Gene
      based tests of rare/common variants were significant at the nominal 5% level for
      OBSCN as well as TCAP, DSC2, VCL, NEXN, KCNJ2 and DMD (p = 0.044-0.008). Our
      results suggest that rare and common variants in OBSCN, as well as in other
      genes, could have modifying effects in cardiomyopathy.

PMID- 29367540
TI  - A Multiparametric Approach Based on NT-proBNP, ST2, and Galectin3 for Stratifying
      One Year Prognosis of Chronic Heart Failure Outpatients.
AB  - Galectin-3 and ST2 are emerging biomarkers involved in myocardial fibrosis. We
      evaluate the relevance of a multiparametric biomarker approach based on increased
      serum levels of NT-proBNP, galectin-3, and ST2 in stratifying the prognosis of
      chronic heart failure (CHF) outpatients. In 315 CHF outpatients in stable
      clinical condition clinical and echocardiographic evaluations were performed.
      Routine chemistry and serum levels of NT-proBNP, galectin-3, and ST2 were also
      assessed. During a 12 month follow-up, cardiovascular death, and/or heart failure
      (HF) occurred in 64 patients. The presence of NT-proBNP, galectin-3, and ST2 were
      higher than the recommended cutoffs and were all associated with events at
      univariate Cox regression analysis, as well as in a multivariate analysis
      including the three biomarkers. When a score based on the number of biomarkers
      above the recommended cut-offs was used (in a range of 0-3), it was associated
      with events both with respect to the univariate (HR 2.96, 95% CI 2.21-3.95, p <
      0.001, C-index 0.78) and the multivariate (HR 1.52, 95% CI 1.06-2.17, p: 0.023, C
      index 0.87) analyses, after correction for the variables of a reference model.
      Our results suggest that an easy prognostic approach based on the combination of
      three biomarkers, although with partially-overlapping pathophysiological
      mechanisms, is able to identify patients with the highest risk of heart failure
      progression.

PMID- 29367539
TI  - Multiple Species Comparison of Cardiac Troponin T and Dystrophin: Unravelling the
      DNA behind Dilated Cardiomyopathy.
AB  - Animals have frequently been used as models for human disorders and mutations.
      Following advances in genetic testing and treatment options, and the decreasing
      cost of these technologies in the clinic, mutations in both companion and
      commercial animals are now being investigated. A recent review highlighted the
      genes associated with both human and non-human dilated cardiomyopathy. Cardiac
      troponin T and dystrophin were observed to be associated with both human and
      turkey (troponin T) and canine (dystrophin) dilated cardiomyopathies. This review
      gives an overview of the work carried out in cardiac troponin T and dystrophin to
      date in both human and animal dilated cardiomyopathy.

PMID- 29367541
TI  - Diagnostic Yield of Whole Exome Sequencing in Pediatric Dilated Cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a heritable, genetically heterogeneous disorder
      characterized by progressive heart failure. DCM typically remains clinically
      silent until adulthood, yet symptomatic disease can develop in childhood. We
      sought to identify the genetic basis of pediatric DCM in 15 sporadic and three
      affected-siblings cases, comprised of 21 affected children (mean age, five years)
      whose parents had normal echocardiograms (mean age, 39 years). Twelve underwent
      cardiac transplantation and five died with severe heart failure. Parent-offspring
      whole exome sequencing (WES) data were filtered for rare, deleterious, de novo
      and recessive variants. In prior work, we reported de novo mutations in TNNT2 and
      RRAGC and compound heterozygous mutations in ALMS1 and TAF1A among four cases in
      our cohort. Here, de novo mutations in established DCM genes-RBM20, LMNA, TNNT2,
      and PRDM16-were identified among five additional cases. The RBM20 mutation was
      previously reported in familial DCM. An identical unreported LMNA mutation was
      identified in two unrelated cases, both harboring gene-specific defects in
      cardiomyocyte nuclear morphology. Collectively, WES had a 50% diagnostic yield in
      our cohort, providing an explanation for pediatric heart failure and enabling
      informed family planning. Research is ongoing to discover novel DCM genes among
      the remaining families.

PMID- 29367542
TI  - Insights from Second-Line Treatments for Idiopathic Dilated Cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is an independent nosographic entity
      characterized by left ventricular dilatation and contractile dysfunction leading
      to heart failure (HF). The idiopathic form of DCM (iDCM) occurs in the absence of
      coronaropathy or other known causes of DCM. Despite being different from other
      forms of HF for demographic, clinical, and prognostic features, its current
      pharmacological treatment does not significantly diverge. METHODS: In this study
      we performed a Pubmed library search for placebo-controlled clinical
      investigations and a post-hoc analysis recruiting iDCM from 1985 to 2016. We
      searched for second-line pharmacologic treatments to reconsider drugs for iDCM
      management and pinpoint pathological mechanisms. RESULTS: We found 33 clinical
      studies recruiting a total of 3392 patients of various durations and sizes, as
      well as studies that tested different drug classes (statins, pentoxifylline,
      inotropes). A metanalysis was unfeasible, although a statistical significance for
      changes upon treatment for molecular results, morphofunctional parameters, and
      clinical endpoints was reported. Statins appeared to be beneficial in light of
      their pleiotropic effects; inotropes might be tolerated more for longer times in
      iDCM compared to ischemic patients. General anti-inflammatory therapies do not
      significantly improve outcomes. Metabolic and growth modulation remain appealing
      fields to be investigated. CONCLUSIONS: The evaluation of drug effectiveness
      based on direct clinical benefit is an inductive method providing evidence-based
      insights. This backward approach sheds light on putative and underestimated
      pathologic mechanisms and thus therapeutic targets for iDCM management.

PMID- 29367544
TI  - Establishing the Embryonic Axes: Prime Time for Teratogenic Insults.
AB  - A long standing axiom in the field of teratology states that the teratogenic
      period, when most birth defects are produced, occurs during the third to eighth
      weeks of development post-fertilization. Any insults prior to this time are
      thought to result in a slowing of embryonic growth from which the conceptus
      recovers or death of the embryo followed by spontaneous abortion. However, new
      insights into embryonic development during the first two weeks, including
      formation of the anterior-posterior, dorsal-ventral, and left-right axes,
      suggests that signaling pathways regulating these processes are prime targets for
      genetic and toxic insults. Establishment of the left-right (laterality) axis is
      particularly sensitive to disruption at very early stages of development and
      these perturbations result in a wide variety of congenital malformations,
      especially heart defects. Thus, the time for teratogenic insults resulting in
      birth defects should be reset to include the first two weeks of development.

PMID- 29367543
TI  - Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical
      Phenotype.
AB  - Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked
      dilated cardiomyopathy (XL-DCM) consist of a unique clinical entity, the
      dystrophinopathies, which are due to variable mutations in the dystrophin gene.
      Dilated cardiomyopathy (DCM) is a common complication of dystrophinopathies, but
      the onset, progression, and severity of heart disease differ among these
      subgroups. Extensive molecular genetic studies have been conducted to assess
      genotype-phenotype correlation in DMD, BMD, and XL-DCM to understand the
      underlying mechanisms of these diseases, but the results are not always
      conclusive, suggesting the involvement of complex multi-layers of pathological
      processes that generate the final clinical phenotype. Dystrophin protein is a
      part of dystrophin-glycoprotein complex (DGC) that is localized in skeletal
      muscles, myocardium, smooth muscles, and neuronal tissues. Diversity of cardiac
      phenotype in dystrophinopathies suggests multiple layers of pathogenetic
      mechanisms in forming dystrophic cardiomyopathy. In this review article, we
      review the complex molecular interactions involving the pathogenesis of
      dystrophic cardiomyopathy, including primary gene mutations and loss of
      structural integrity, secondary cellular responses, and certain epigenetic and
      other factors that modulate gene expressions. Involvement of epigenetic gene
      regulation appears to lead to specific cardiac phenotypes in dystrophic hearts.

PMID- 29367546
TI  - Strategy for Identification of Phosphorylation Levels of Low Abundance Proteins
      in Vivo for Which Antibodies Are not Available.
AB  - Protein function is mainly modulated by dynamic reversible or irreversible post
      translational modifications. Among them, the identification of protein
      phosphorylation sites and changes in phosphorylation levels in vivo are of
      considerable interest for a better understanding of the protein function. Thus,
      effective strategies for the quantitative determination of phosphorylation
      degrees for low abundant proteins, for which antibodies are not available, are
      required in order to evaluate the functional regulation of proteins attributed to
      phosphorylation. In this study, we used the heart beta1-adrenergic receptor
      (Adrb1) as a model protein and developed FLAG-Adrb1 knock-in mice, in which the
      FLAG tag was inserted at the N-terminus of Adrb1. The phosphorylation sites and
      levels of Adrb1 in the heart were elucidated by immuno-affinity purification
      followed by quantitative mass spectrometry analysis using ion intensity ratio of
      the phosphorylated peptide versus corresponding unphosphorylated peptide. The
      phosphorylation levels at Ser274 and Ser462 of Adrb1 were approximately 0.25 and
      0.0023. This effective strategy should be useful for not only analyzing site
      specific phosphorylation levels of target proteins, but also quantifying the
      expression levels of proteins of interest when appropriate antibodies are not
      available.

PMID- 29367545
TI  - Multiple Roles of Pitx2 in Cardiac Development and Disease.
AB  - Cardiac development is a complex morphogenetic process initiated as bilateral
      cardiogenic mesoderm is specified at both sides of the gastrulating embryo. Soon
      thereafter, these cardiogenic cells fuse at the embryonic midline configuring a
      symmetrical linear cardiac tube. Left/right bilateral asymmetry is first detected
      in the forming heart as the cardiac tube bends to the right, and subsequently,
      atrial and ventricular chambers develop. Molecular signals emanating from the
      node confer distinct left/right signalling pathways that ultimately lead to
      activation of the homeobox transcription factor Pitx2 in the left side of
      distinct embryonic organ anlagen, including the developing heart. Asymmetric
      expression of Pitx2 has therefore been reported during different cardiac
      developmental stages, and genetic deletion of Pitx2 provided evidence of key
      regulatory roles of this transcription factor during cardiogenesis and thus
      congenital heart diseases. More recently, impaired Pitx2 function has also been
      linked to arrhythmogenic processes, providing novel roles in the adult heart. In
      this manuscript, we provide a state-of-the-art review of the fundamental roles of
      Pitx2 during cardiogenesis, arrhythmogenesis and its contribution to congenital
      heart diseases.

PMID- 29367547
TI  - The Dark Side of the Moon: The Right Ventricle.
AB  - The aim of this review article is to summarize current knowledge of the
      pathophysiology underlying right ventricular failure (RVF), focusing, in
      particular, on right ventricular assessment and prognosis. The right ventricle
      (RV) can tolerate volume overload well, but is not able to sustain pressure
      overload. Right ventricular hypertrophy (RVH), as a response to increased
      afterload, can be adaptive or maladaptive. The easiest and most common way to
      assess the RV is by two-dimensional (2D) trans-thoracic echocardiography
      measuring surrogate indexes, such as tricuspid annular plane systolic excursion
      (TAPSE), fractional area change (FAC), and tissue Doppler velocity of the lateral
      aspect of the tricuspid valvular plane. However, both volumes and function are
      better estimated by 3D echocardiography and cardiac magnetic resonance (CMR). The
      prognostic role of the RV in heart failure (HF), pulmonary hypertension (PH),
      acute myocardial infarction (AMI), and cardiac surgery has been overlooked for
      many years. However, several recent studies have placed much greater importance
      on the RV in prognostic assessments. In conclusion, RV dimensions and function
      should be routinely assessed in cardiovascular disease, as RVF has a significant
      impact on disease prognosis. In the presence of RVF, different therapeutic
      approaches, either pharmacological or surgical, may be beneficial.

PMID- 29367548
TI  - Kinking and Torsion Can Significantly Improve the Efficiency of Valveless Pumping
      in Periodically Compressed Tubular Conduits. Implications for Understanding of
      the Form-Function Relationship of Embryonic Heart Tubes.
AB  - Valveless pumping phenomena (peristalsis, Liebau-effect) can generate
      unidirectional fluid flow in periodically compressed tubular conduits. Early
      embryonic hearts are tubular conduits acting as valveless pumps. It is unclear
      whether such hearts work as peristaltic or Liebau-effect pumps. During the
      initial phase of its pumping activity, the originally straight embryonic heart is
      subjected to deforming forces that produce bending, twisting, kinking, and
      coiling. This deformation process is called cardiac looping. Its function is
      traditionally seen as generating a configuration needed for establishment of
      correct alignments of pulmonary and systemic flow pathways in the mature heart of
      lung-breathing vertebrates. This idea conflicts with the fact that cardiac
      looping occurs in all vertebrates, including gill-breathing fishes. We speculate
      that looping morphogenesis may improve the efficiency of valveless pumping. To
      test the physical plausibility of this hypothesis, we analyzed the pumping
      performance of a Liebau-effect pump in straight and looped (kinked)
      configurations. Compared to the straight configuration, the looped configuration
      significantly improved the pumping performance of our pump. This shows that
      looping can improve the efficiency of valveless pumping driven by the Liebau
      effect. Further studies are needed to clarify whether this finding may have
      implications for understanding of the form-function relationship of embryonic
      hearts.

PMID- 29367549
TI  - Growth and Morphogenesis during Early Heart Development in Amniotes.
AB  - In this review, we will focus on the growth and morphogenesis of the developing
      heart, an aspect of cardiovascular development to which Antoon Moorman and
      colleagues have extensively contributed. Over the last decades, genetic studies
      and characterization of regionally regulated gene programs have provided abundant
      novel insights into heart development essential to understand the basis of
      congenital heart disease. Heart morphogenesis, however, is inherently a complex
      and dynamic three-dimensional process and we are far from understanding its
      cellular basis. Here, we discuss recent advances in studying heart morphogenesis
      and regionalization under the light of the pioneering work of Moorman and
      colleagues, which allowed the reinterpretation of regional gene expression
      patterns under a new morphogenetic framework. Two aspects of early heart
      formation will be discussed in particular: (1) the initial formation of the heart
      tube and (2) the formation of the cardiac chambers by the ballooning process.
      Finally, we emphasize that in addition to analyses based on fixed samples, new
      approaches including clonal analysis, single-cell sequencing, live-imaging and
      quantitative analysis of the data generated will likely lead to novel insights in
      understanding early heart tube regionalization and morphogenesis in the near
      future.

PMID- 29367552
TI  - The Role of Cerl2 in the Establishment of Left-Right Asymmetries during Axis
      Formation and Heart Development.
AB  - The formation of the asymmetric left-right (LR) body axis is one of the
      fundamental aspects of vertebrate embryonic development, and one still raising
      passionate discussions among scientists. Although the conserved role of nodal is
      unquestionable in this process, several of the details around this signaling
      cascade are still unanswered. To further understand this mechanism, we have been
      studying Cerberus-like 2 (Cerl2), an inhibitor of Nodal, and its role in the
      generation of asymmetries in the early vertebrate embryo. The absence of Cerl2
      results in a wide spectrum of malformations commonly known as heterotaxia, which
      comprises defects in either global organ position (e.g., situs inversus totalis),
      reversed orientation of at least one organ (e.g., situs ambiguus), and mirror
      images of usually asymmetric paired organs (e.g., left or right isomerisms of the
      lungs). Moreover, these laterality defects are frequently associated with
      congenital heart diseases (e.g., transposition of the great arteries, or
      atrioventricular septal defects). Here, reviewing the knowledge on the
      establishment of LR asymmetry in mouse embryos, the emerging conclusion is that
      as necessary as is the activation of the Nodal signaling cascade, the tight
      control that Cerl2-mediates on Nodal signaling is equally important, and that
      generates a further regionalized LR genetic program in the proper time and space.

PMID- 29367551
TI  - The Potential of a Novel Class of EPAC-Selective Agonists to Combat
      Cardiovascular Inflammation.
AB  - The cyclic 3',5'-adenosine monophosphate (cAMP) sensor enzyme, EPAC1, is a
      candidate drug target in vascular endothelial cells (VECs) due to its ability to
      attenuate proinflammatory cytokine signalling normally associated with
      cardiovascular diseases (CVDs), including atherosclerosis. This is through the
      EPAC1-dependent induction of the suppressor of cytokine signalling gene, SOCS3,
      which targets inflammatory signalling proteins for ubiquitinylation and
      destruction by the proteosome. Given this important role for the EPAC1/SOCS3
      signalling axis, we have used high throughput screening (HTS) to identify small
      molecule EPAC1 regulators and have recently isolated the first known non-cyclic
      nucleotide (NCN) EPAC1 agonist, I942. I942 therefore represents the first in
      class, isoform selective EPAC1 activator, with the potential to suppress pro
      inflammatory cytokine signalling with a reduced risk of side effects associated
      with general cAMP-elevating agents that activate multiple response pathways. The
      development of augmented I942 analogues may therefore provide improved research
      tools to validate EPAC1 as a potential therapeutic target for the treatment of
      chronic inflammation associated with deadly CVDs.

PMID- 29367550
TI  - The Physiopathology of Cardiorenal Syndrome: A Review of the Potential
      Contributions of Inflammation.
AB  - Inter-organ crosstalk plays an essential role in the physiological homeostasis of
      the heart and other organs, and requires a complex interaction between a host of
      cellular, molecular, and neural factors. Derangements in these interactions can
      initiate multi-organ dysfunction. This is the case, for instance, in the heart or
      kidneys where a pathological alteration in one organ can unfavorably affect
      function in another distant organ; attention is currently being paid to
      understanding the physiopathological consequences of kidney dysfunction on
      cardiac performance that lead to cardiorenal syndrome. Different cardiorenal
      connectors (renin-angiotensin or sympathetic nervous system activation,
      inflammation, uremia, etc.) and non-traditional risk factors potentially
      contribute to multi-organ failure. Of these, inflammation may be crucial as
      inflammatory cells contribute to over-production of eicosanoids and lipid second
      messengers that activate intracellular signaling pathways involved in
      pathogenesis. Indeed, inflammation biomarkers are often elevated in patients with
      cardiac or renal dysfunction. Epigenetics, a dynamic process that regulates gene
      expression and function, is also recognized as an important player in single
      organ disease. Principal epigenetic modifications occur at the level of DNA
      (i.e., methylation) and histone proteins; aberrant DNA methylation is associated
      with pathogenesis of organ dysfunction through a number of mechanisms
      (inflammation, nitric oxide bioavailability, endothelin, etc.). Herein, we focus
      on the potential contribution of inflammation in pathogenesis of cardiorenal
      syndrome.

PMID- 29367553
TI  - Hemodynamics Modify Collagen Deposition in the Early Embryonic Chicken Heart
      Outflow Tract.
AB  - Blood flow is critical for normal cardiac development. Hemodynamic stimuli
      outside of normal ranges can lead to overt cardiac defects, but how early heart
      tissue remodels in response to altered hemodynamics is poorly understood. This
      study investigated changes in tissue collagen in response to hemodynamic overload
      in the chicken embryonic heart outflow tract (OFT) during tubular heart stages
      (HH18 to HH24, ~24 h). A suture tied around the OFT at HH18 was tightened to
      constrict the lumen for ~24 h (constriction range at HH24: 15-60%). Expression of
      fibril collagens I and III and fibril organizing collagens VI and XIV were
      quantified at the gene and protein levels via qPCR and quantitative
      immunofluorescence. Collagen I was slightly elevated upstream of the band and in
      the cushions in banded versus control OFTs. Changes in collagen III were not
      observed. Collagen VI deposition was elevated downstream of the band, but not
      overall. Collagen XIV deposition increased throughout the OFT, and strongly
      correlated to lumen constriction. Interestingly, organization of collagen I
      fibrils was observed for the tighter banded embryos in regions that also showed
      increase in collagen XIV deposition, suggesting a potentially key role for
      collagens I and XIV in the structural adaptation of embryonic heart tissue to
      hemodynamic overload.

PMID- 29367554
TI  - Segregation of Central Ventricular Conduction System Lineages in Early SMA+
      Cardiomyocytes Occurs Prior to Heart Tube Formation.
AB  - The cardiac conduction system (CCS) transmits electrical activity from the atria
      to the ventricles to coordinate heartbeats. Atrioventricular conduction diseases
      are often associated with defects in the central ventricular conduction system
      comprising the atrioventricular bundle (AVB) and right and left branches (BBs).
      Conducting and contractile working myocytes share common cardiomyogenic
      progenitors, however the time at which the CCS lineage becomes specified is
      unclear. In order to study the fate and the contribution to the CCS of
      cardiomyocytes during early heart tube formation, we performed a genetic lineage
      analysis using a Sma-CreERT2 mouse line. Lineage tracing experiments reveal a
      sequential contribution of early Sma expressing cardiomyocytes to different
      cardiac compartments, labeling at embryonic day (E) 7.5 giving rise to the
      interventricular septum and apical left ventricular myocardium. Early Sma
      expressing cardiomyocytes contribute to the AVB, BBs and left ventricular
      Purkinje fibers. Clonal analysis using the R26-confetti reporter mouse crossed
      with Sma-CreERT2 demonstrates that early Sma expressing cardiomyocytes include
      cells exclusively fated to give rise to the AVB. In contrast, lineage segregation
      is still ongoing for the BBs at E7.5. Overall this study highlights the early
      segregation of the central ventricular conduction system lineage within
      cardiomyocytes at the onset of heart tube formation.

PMID- 29367555
TI  - Long-term Benefits of Risk Factor Reduction in Takotsubo Cardiomyopathy.-A
      Comment on Khalighi et al. Entitled "Takotsubo Cardiomyopathy: A Long Term Follow
      up Shows Benefit with Risk Factor Reduction", J. Cardiovasc. Dev. Dis., 2015, 2,
      273-281.
AB  - Takotsubo cardiomyopathy (TC) or stress-induced cardiomyopathy is also popularly
      referred to as "broken heart syndrome" or "apical ballooning syndrome". [...].

PMID- 29367556
TI  - Response to Ponamgi et al. Comments on Khalighi et al. Takotsubo Cardiomyopathy:
      A Long Term Follow-up Shows Benefit with Risk Factor Reduction. J. Cardiovasc.
      Dev. Dis., 2015, 2, 273-281.
AB  - We appreciate the thorough response given by Ponagmi et al. [1], who rightly
      point out that the pathophysiology and modifiable risk factors of Takotsubo
      Cardiomyopathy (TC) have yet to be unequivocally established. [...].

PMID- 29367559
TI  - Factors Affecting Hypertension among the Malaysian Elderly.
AB  - Hypertension is a common chronic disease in the elderly. This study aimed to
      determine the effects of age, ethnicity, gender, education, marital status,
      nutritional parameters, and blood elements on the risk of high blood pressure in
      the Malaysian elderly. This research was conducted on a group of 2322 non
      institutionalized Malaysian elderly. The hierarchy binary logistic regression
      analysis was applied to estimate the risk of hypertension in respondents.
      Approximately, 45.61% of subjects had hypertension. The findings indicated that
      the female gender (Odds ratio (OR) = 1.54), an increase in body weight (OR =
      1.61), and an increase in the blood levels of albumin (OR = 1.51), glucose (OR =
      1.92), and triglycerides (OR = 1.27) significantly increased the risk of
      hypertension in subjects (p < 0.05). Conversely, an increase in both dietary
      carbohydrates (OR = 0.74), and blood cholesterol level (OR = 0.42) significantly
      reduced the risk of hypertension in samples (p < 0.05). Furthermore, the results
      showed that ethnicity was a non-relevant factor to increase the risk of
      hypertension in subjects. It was concluded that female gender, an increase in
      body weight, and an increase in the blood levels of glucose, triglycerides, and
      albumin enhanced the risk of high blood pressure in the Malaysian elderly. In
      addition, an increase in both dietary carbohydrates and blood cholesterol level
      decreased hypertension in subjects.

PMID- 29367558
TI  - Drosophila in the Heart of Understanding Cardiac Diseases: Modeling
      Channelopathies and Cardiomyopathies in the Fruitfly.
AB  - Cardiovascular diseases and, among them, channelopathies and cardiomyopathies are
      a major cause of death worldwide. The molecular and genetic defects underlying
      these cardiac disorders are complex, leading to a large range of structural and
      functional heart phenotypes. Identification of molecular and functional
      mechanisms disrupted by mutations causing channelopathies and cardiomyopathies is
      essential to understanding the link between an altered gene and clinical
      phenotype. The development of animal models has been proven to be efficient for
      functional studies in channelopathies and cardiomyopathies. In particular, the
      Drosophila model has been largely applied for deciphering the molecular and
      cellular pathways affected in these inherited cardiac disorders and for
      identifying their genetic modifiers. Here we review the utility and the main
      contributions of the fruitfly models for the better understanding of
      channelopathies and cardiomyopathies. We also discuss the investigated
      pathological mechanisms and the discoveries of evolutionarily conserved pathways
      which reinforce the value of Drosophila in modeling human cardiac diseases.

PMID- 29367560
TI  - TLR-4 and CD14 Genotypes and Soluble CD14: Could They Predispose to Coronary
      Atherosclerosis?
AB  - BACKGROUND: Inflammatory mechanisms are key to the pathogenesis of
      atherosclerosis. Functional polymorphisms of TLR-4, Asp299Gly and Thr399Ile, CD14
      promoter area C260T polymorphism and plasma levels of soluble CD14 are studied in
      subjects with Coronary Artery Disease (CAD). METHODS: DNA was obtained from 100
      human paraffin-embedded aortic specimens, from cadavers with known coronary
      atheromatosis (Group A) and 100 blood samples from patients with CAD, as detected
      by cardiac Multi-Detector-row-Computed-Tomography (MDCT) (Group B). Our control
      group consisted of 100 healthy individuals (Group C). Genotyping was performed by
      Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR).
      Plasma levels of sCD14 were measured with ELISA. RESULTS: For TLR-4 Asp299Gly and
      Thr399Ile polymorphisms, no statistically significant differences were observed.
      Regarding the C260T polymorphism, frequencies of T allele were significantly
      higher in the control group compared to the case group (p = 0.05). The Odds Ratio
      (OR) showed statistically significant association of TT genotype with healthy
      individuals (OR 0.25, 95% Confidence Interval CI 0.10-0.62, p = 0.0017). Plasma
      levels of sCD14 in patients with CAD (mean value = 1.35 MUg/mL) were reduced when
      compared to reference value. CONCLUSIONS: The studied polymorphisms ofTLR-4
      showed no association with CAD. Conversely, the functional polymorphism of CD14
      has a statistically significant difference in expression between healthy and
      affected by CAD individuals.

PMID- 29367562
TI  - The "Dead-End Tract" and Its Role in Arrhythmogenesis.
AB  - Idiopathic outflow tract ventricular arrhythmias (VAs) represent a significant
      proportion of all VAs. The mechanism is thought to be catecholamine-mediated
      delayed after depolarizations and triggered activity, although other etiologies
      should be considered. In the adult cardiac conduction system it has been
      demonstrated that sometimes an embryonic branch, the so-called "dead-end tract",
      persists beyond the bifurcation of the right and left bundle branch (LBB).
      Several findings suggest an involvement of this tract in idiopathic VAs (IVAs).
      The aim of this review is to summarize our current knowledge and the possible
      clinical significance of this tract.

PMID- 29367561
TI  - Probing the Electrophysiology of the Developing Heart.
AB  - Many diseases that result in dysfunction and dysmorphology of the heart originate
      in the embryo. However, the embryonic heart presents a challenging subject for
      study: especially challenging is its electrophysiology. Electrophysiological
      maturation of the embryonic heart without disturbing its physiological function
      requires the creation and deployment of novel technologies along with the use of
      classical techniques on a range of animal models. Each tool has its strengths and
      limitations and has contributed to making key discoveries to expand our
      understanding of cardiac development. Further progress in understanding the
      mechanisms that regulate the normal and abnormal development of the
      electrophysiology of the heart requires integration of this functional
      information with the more extensively elucidated structural and molecular
      changes.

PMID- 29367563
TI  - The Early Stages of Heart Development: Insights from Chicken Embryos.
AB  - The heart is the first functioning organ in the developing embryo and a detailed
      understanding of the molecular and cellular mechanisms involved in its formation
      provides insights into congenital malformations affecting its function and
      therefore the survival of the organism. Because many developmental mechanisms are
      highly conserved, it is possible to extrapolate from observations made in
      invertebrate and vertebrate model organisms to humans. This review will highlight
      the contributions made through studying heart development in avian embryos,
      particularly the chicken. The major advantage of chick embryos is their
      accessibility for surgical manipulation and functional interference approaches,
      both gain- and loss-of-function. In addition to experiments performed in ovo, the
      dissection of tissues for ex vivo culture, genomic, or biochemical approaches is
      straightforward. Furthermore, embryos can be cultured for time-lapse imaging,
      which enables tracking of fluorescently labeled cells and detailed analysis of
      tissue morphogenesis. Owing to these features, investigations in chick embryos
      have led to important discoveries, often complementing genetic studies in mice
      and zebrafish. As well as including some historical aspects, we cover here some
      of the crucial advances made in understanding early heart development using the
      chicken model.

PMID- 29367564
TI  - On the Morphology of the Drosophila Heart.
AB  - The circulatory system of Drosophilamelanogaster represents an easily amenable
      genetic model whose analysis at different levels, i.e., from single molecules up
      to functional anatomy, has provided new insights into general aspects of
      cardiogenesis, heart physiology and cardiac aging, to name a few examples. In
      recent years, the Drosophila heart has also attracted the attention of
      researchers in the field of biomedicine. This development is mainly due to the
      fact that several genes causing human heart disease are also present in
      Drosophila, where they play the same or similar roles in heart development,
      maintenance or physiology as their respective counterparts in humans. This review
      will attempt to briefly introduce the anatomy of the Drosophila circulatory
      system and then focus on the different cell types and non-cellular tissue that
      constitute the heart.

PMID- 29367565
TI  - Postnatal Cardiac Autonomic Nervous Control in Pediatric Congenital Heart
      Disease.
AB  - Congenital heart disease is the most common congenital defect. During childhood,
      survival is generally good but, in adulthood, late complications are not
      uncommon. Abnormal autonomic control in children with congenital heart disease
      may contribute considerably to the pathophysiology of these long term sequelae.
      This narrative review of 34 studies aims to summarize current knowledge on
      function of the autonomic nervous system in children with a congenital heart
      defect. Large scale studies that measure both branches of the nervous system for
      prolonged periods of time in well-defined patient cohorts in various phases of
      childhood and adolescence are currently lacking. Pending such studies, there is
      not yet a good grasp on the extent and direction of sympathetic and
      parasympathetic autonomic function in pediatric congenital heart disease.
      Longitudinal studies in homogenous patient groups linking autonomic nervous
      system function and clinical outcome are warranted.

PMID- 29367566
TI  - Of Tracts, Rings, Nodes, Cusps, Sinuses, and Arrhythmias-A Comment on Szili-Torok
      et al.'s Paper Entitled "The 'Dead-End Tract' and Its Role in Arrhythmogenesis".
      J. Cardiovasc. Dev. Dis. 2016, 3, 11.
AB  - In the review, now published as part of the special issue devoted to the
      development of the conduction tissues, de Vries and his colleagues discuss the
      potential role of the so-called "dead-end tract" as a substrate for
      arrhythmogenesis [1].[...].

PMID- 29367568
TI  - The Popeye Domain Containing Genes and Their Function in Striated Muscle.
AB  - The Popeye domain containing (POPDC) genes encode a novel class of cAMP effector
      proteins, which are abundantly expressed in heart and skeletal muscle. Here, we
      will review their role in striated muscle as deduced from work in cell and animal
      models and the recent analysis of patients carrying a missense mutation in
      POPDC1. Evidence suggests that POPDC proteins control membrane trafficking of
      interacting proteins. Furthermore, we will discuss the current catalogue of
      established protein-protein interactions. In recent years, the number of POPDC
      interacting proteins has been rising and currently includes ion channels (TREK
      1), sarcolemma-associated proteins serving functions in mechanical stability
      (dystrophin), compartmentalization (caveolin 3), scaffolding (ZO-1), trafficking
      (NDRG4, VAMP2/3) and repair (dysferlin) or acting as a guanine nucleotide
      exchange factor for Rho-family GTPases (GEFT). Recent evidence suggests that
      POPDC proteins might also control the cellular level of the nuclear proto
      oncoprotein c-Myc. These data suggest that this family of cAMP-binding proteins
      probably serves multiple roles in striated muscle.

PMID- 29367567
TI  - A Matter of the Heart: The African Clawed Frog Xenopus as a Model for Studying
      Vertebrate Cardiogenesis and Congenital Heart Defects.
AB  - The African clawed frog, Xenopus, is a valuable non-mammalian model organism to
      investigate vertebrate heart development and to explore the underlying molecular
      mechanisms of human congenital heart defects (CHDs). In this review, we outline
      the similarities between Xenopus and mammalian cardiogenesis, and provide an
      overview of well-studied cardiac genes in Xenopus, which have been associated
      with congenital heart conditions. Additionally, we highlight advantages of
      modeling candidate genes derived from genome wide association studies (GWAS) in
      Xenopus and discuss commonly used techniques.

PMID- 29367569
TI  - Vascular Development and Regeneration in the Mammalian Heart.
AB  - Cardiovascular diseases including coronary artery disease are the leading cause
      of death worldwide. Unraveling the developmental origin of coronary vessels could
      offer important therapeutic implications for treatment of cardiovascular
      diseases. The recent identification of the endocardial source of coronary vessels
      reveals a heterogeneous origin of coronary arteries in the adult heart. In this
      review, we will highlight recent advances in finding the sources of coronary
      vessels in the mammalian heart from lineage-tracing models as well as
      differentiation studies using pluripotent stem cells. Moreover, we will also
      discuss how we induce neovascularization in the damaged heart through transient
      yet highly efficient expression of VEGF-modified mRNAs as a potentially
      therapeutic delivery platform.

PMID- 29367570
TI  - Stem Cell Therapy and Congenital Heart Disease.
AB  - For more than a decade, stem cell therapy has been the focus of intensive efforts
      for the treatment of adult heart disease, and now has promise for treating the
      pediatric population. On the basis of encouraging results in the adult field, the
      application of stem cell-based strategies in children with congenital heart
      disease (CHD) opens a new therapy paradigm. To date, the safety and efficacy of
      stem cell-based products to promote cardiac repair and recovery in dilated
      cardiomyopathy and structural heart disease in infants have been primarily
      demonstrated in scattered clinical case reports, and supported by a few relevant
      pre-clinical models. Recently the TICAP trial has shown the safety and
      feasibility of intracoronary infusion of autologous cardiosphere-derived cells in
      children with hypoplastic left heart syndrome. A focus on preemptive cardiac
      regeneration in the pediatric setting may offer new insights as to the timing of
      surgery, location of cell-based delivery, and type of cell-based regeneration
      that could further inform acquired cardiac disease applications. Here, we review
      the current knowledge on the field of stem cell therapy and tissue engineering in
      children with CHD, and discuss the gaps and future perspectives on cell-based
      strategies to treat patients with CHD.

PMID- 29367571
TI  - Heart Failure in Patients with Preserved Ejection Fraction: Questions Concerning
      Clinical Progression.
AB  - Over the last two decades, important advances have been made in explaining some
      pathophysiological aspects of heart failure with preserved ejection fraction
      (HFpEF) with repercussions for the successful clinical management of the
      syndrome. Despite these gains, our knowledge for the natural history of clinical
      progression from the pre-clinical diastolic dysfunction (PDD) until the final
      clinical stages is significantly limited. The subclinical progression of PDD to
      the clinical phenotype of HFpEF and the further clinical progression to some more
      complex clinical models with multi-organ involvement, similar to heart failure
      with reduced ejection fraction (HFrEF), continue to be poorly understood.
      Prospective studies are needed to elucidate the natural history of clinical
      progression in patients with HFpEF and to identify the exact left ventricular
      remodeling mechanism that underlies this progression.

PMID- 29367573
TI  - Large Mammalian Animal Models of Heart Disease.
AB  - Due to the biological complexity of the cardiovascular system, the animal model
      is an urgent pre-clinical need to advance our knowledge of cardiovascular disease
      and to explore new drugs to repair the damaged heart. Ideally, a model system
      should be inexpensive, easily manipulated, reproducible, a biological
      representative of human disease, and ethically sound. Although a larger animal
      model is more expensive and difficult to manipulate, its genetic, structural,
      functional, and even disease similarities to humans make it an ideal model to
      first consider. This review presents the commonly-used large animals-dog, sheep,
      pig, and non-human primates-while the less-used other large animals-cows, horses
      are excluded. The review attempts to introduce unique points for each species
      regarding its biological property, degrees of susceptibility to develop certain
      types of heart diseases, and methodology of induced conditions. For example, dogs
      barely develop myocardial infarction, while dilated cardiomyopathy is developed
      quite often. Based on the similarities of each species to the human, the model
      selection may first consider non-human primates-pig, sheep, then dog-but it also
      depends on other factors, for example, purposes, funding, ethics, and policy. We
      hope this review can serve as a basic outline of large animal models for
      cardiovascular researchers and clinicians.

PMID- 29367572
TI  - Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular
      Building Blocks during Development.
AB  - The autonomic nervous system (cANS) is essential for proper heart function, and
      complications such as heart failure, arrhythmias and even sudden cardiac death
      are associated with an altered cANS function. A changed innervation state may
      underlie (part of) the atrial and ventricular arrhythmias observed after
      myocardial infarction. In other cardiac diseases, such as congenital heart
      disease, autonomic dysfunction may be related to disease outcome. This is also
      the case after heart transplantation, when the heart is denervated. Interest in
      the origin of the autonomic nerve system has renewed since the role of autonomic
      function in disease progression was recognized, and some plasticity in autonomic
      regeneration is evident. As with many pathological processes, autonomic
      dysfunction based on pathological innervation may be a partial recapitulation of
      the early development of innervation. As such, insight into the development of
      cardiac innervation and an understanding of the cellular background contributing
      to cardiac innervation during different phases of development is required. This
      review describes the development of the cANS and focuses on the cellular
      contributions, either directly by delivering cells or indirectly by secretion of
      necessary factors or cell-derivatives.

PMID- 29367575
TI  - Genetic and Epigenetic Mechanisms Linking Air Pollution and Congenital Heart
      Disease.
AB  - Epidemiological studies strongly suggest that parental air pollutants exposure
      during the periconceptional period may play a major role in causing fetal/newborn
      malformations, including a frequent heterogeneity in the methods applied and a
      difficulty in estimating the clear effect of environmental toxicants. Moreover,
      only some couples exposed to toxicants during the pre-conception period give
      birth to a child with congenital anomalies. The reasons for such phenomena remain
      elusive but they can be explained by the individual, innate ability to metabolize
      these contaminants that eventually defines the ultimate dose of a biological
      active toxicant. In this paper, we reviewed the major evidence regarding the role
      of parental air pollutant exposure on congenital heart disease (CHD) risk as well
      as the modulating effect on detoxification systems. Finally, major epigenetic
      alterations induced by adverse environment contaminants have been revised as
      possible mechanisms altering a correct heart morphogenesis.

PMID- 29367574
TI  - Myocarditis in Paediatric Patients: Unveiling the Progression to Dilated
      Cardiomyopathy and Heart Failure.
AB  - Myocarditis is a challenging and potentially life-threatening disease associated
      with high morbidity in some paediatric patients, due to its ability to present as
      an acute and fulminant disease and to ultimately progress to dilated
      cardiomyopathy. It has been described as an inflammatory disease of the
      myocardium caused by diverse aetiologies. Viral infection is the most frequent
      cause of myocarditis in developed countries, but bacterial and protozoal
      infections or drug hypersensitivity may also be causative agents. The prompt
      diagnosis in paediatric patients is difficult, as the spectrum of clinical
      manifestation can range from no myocardial dysfunction to sudden cardiac death.
      Recent studies on myocarditis pathogenesis have revealed a triphasic nature of
      this disease, which influences the diagnostic and therapeutic strategies to adopt
      in each patient. Endomyocardial biopsy remains the gold standard for diagnosing
      myocarditis, and several non-invasive diagnostic tools can be used to support the
      diagnosis. Intravenous immunoglobulin has become part of routine practice in the
      treatment of myocarditis in paediatric patients at many centres, but its true
      effect on the cardiac function has been the target of many studies. The aim of
      this review is to approach the recently discovered facets of paediatric
      myocarditis regarding its progression to dilated cardiomyopathy.

PMID- 29367576
TI  - Management of Mechanical Ventilation in Decompensated Heart Failure.
AB  - Mechanical ventilation (MV) is a life-saving intervention for respiratory
      failure, including decompensated congestive heart failure. MV can reduce
      ventricular preload and afterload, decrease extra-vascular lung water, and
      decrease the work of breathing in heart failure. The advantages of positive
      pressure ventilation must be balanced with potential harm from MV: volutrauma,
      hyperoxia-induced injury, and difficulty assessing readiness for liberation. In
      this review, we will focus on cardiac, pulmonary, and broader effects of MV on
      patients with decompensated HF, focusing on practical considerations for
      management and supporting evidence.

PMID- 29367577
TI  - Current Perspectives in Cardiac Laterality.
AB  - The heart is the first organ to break symmetry in the developing embryo and onset
      of dextral looping is the first indication of this event. Looping is a complex
      process that progresses concomitantly to cardiac chamber differentiation and
      ultimately leads to the alignment of the cardiac regions in their final topology.
      Generation of cardiac asymmetry is crucial to ensuring proper form and consequent
      functionality of the heart, and therefore it is a highly regulated process. It
      has long been known that molecular left/right signals originate far before
      morphological asymmetry and therefore can direct it. The use of several animal
      models has led to the characterization of a complex regulatory network, which
      invariably converges on the Tgf-beta signaling molecule Nodal and its downstream
      target, the homeobox transcription factor Pitx2. Here, we review current data on
      the cellular and molecular bases of cardiac looping and laterality, and discuss
      the contribution of Nodal and Pitx2 to these processes. A special emphasis will
      be given to the morphogenetic role of Pitx2 and to its modulation of
      transcriptional and functional properties, which have also linked laterality to
      atrial fibrillation.

PMID- 29367578
TI  - Mechanical Circulatory Support for Advanced Heart Failure: Are We about to
      Witness a New "Gold Standard"?
AB  - The impact of left ventricular assist devices (LVADs) for the treatment of
      advanced heart failure has played a significant role as a bridge to transplant
      and more recently as a long-term solution for non-eligible candidates. Continuous
      flow left ventricular assist devices (CF-LVADs), based on axial and centrifugal
      design, are currently the most popular devices in view of their smaller size,
      increased reliability and higher durability compared to pulsatile flow left
      ventricular assist devices (PF-LVADs). The trend towards their use is increasing.
      Therefore, it has become mandatory to understand the physics and the mathematics
      behind their mode of operation for appropriate device selection and simulation
      set up. For this purpose, this review covers some of these aspects. Although very
      successful and technologically advanced, they have been associated with
      complications such as pump thrombosis, haemolysis, aortic regurgitation, gastro
      intestinal bleeding and arterio-venous malformations. There is perception that
      the reduced arterial pulsatility may be responsible for these complications. A
      flow modulation control approach is currently being investigated in order to
      generate pulsatility in rotary blood pumps. Thrombus formation remains the most
      feared complication that can affect clinical outcome. The development of a
      preoperative strategy aimed at the reduction of complications and patient-device
      suitability may be appropriate. Patient-specific modelling based on 3D
      reconstruction from CT-scan combined with computational fluid dynamic studies is
      an attractive solution in order to identify potential areas of stagnation or
      challenging anatomy that could be addressed to achieve the desired outcome. The
      HeartMate II (axial) and the HeartWare HVAD (centrifugal) rotary blood pumps have
      been now used worldwide with proven outcome. The HeartMate III (centrifugal) is
      now emerging as the new promising device with encouraging preliminary results.
      There are now enough pumps on the market: it is time to focus on the
      complications in order to achieve the full potential and selling-point of this
      type of technology for the treatment of the increasing heart failure patient
      population.

PMID- 29367579
TI  - Vertebrate Left-Right Asymmetry: What Can Nodal Cascade Gene Expression Patterns
      Tell Us?
AB  - Laterality of inner organs is a wide-spread characteristic of vertebrates and
      beyond. It is ultimately controlled by the left-asymmetric activation of the
      Nodal signaling cascade in the lateral plate mesoderm of the neurula stage
      embryo, which results from a cilia-driven leftward flow of extracellular fluids
      at the left-right organizer. This scenario is widely accepted for laterality
      determination in wildtype specimens. Deviations from this norm come in different
      flavors. At the level of organ morphogenesis, laterality may be inverted (situs
      inversus) or non-concordant with respect to the main body axis (situs ambiguus or
      heterotaxia). At the level of Nodal cascade gene activation, expression may be
      inverted, bilaterally induced, or absent. In a given genetic situation, patterns
      may be randomized or predominantly lacking laterality (absence or bilateral
      activation). We propose that the distributions of patterns observed may be
      indicative of the underlying molecular defects, with randomizations being
      primarily caused by defects in the flow-generating ciliary set-up, and
      symmetrical patterns being the result of impaired flow sensing, on the left, the
      right, or both sides. This prediction, the reasoning of which is detailed in this
      review, pinpoints functions of genes whose role in laterality determination have
      remained obscure.

PMID- 29367580
TI  - Function of Adenylyl Cyclase in Heart: the AKAP Connection.
AB  - Cyclic adenosine monophosphate (cAMP), synthesized by adenylyl cyclase (AC), is a
      universal second messenger that regulates various aspects of cardiac physiology
      from contraction rate to the initiation of cardioprotective stress response
      pathways. Local pools of cAMP are maintained by macromolecular complexes formed
      by A-kinase anchoring proteins (AKAPs). AKAPs facilitate control by bringing
      together regulators of the cAMP pathway including G-protein-coupled receptors,
      ACs, and downstream effectors of cAMP to finely tune signaling. This review will
      summarize the distinct roles of AC isoforms in cardiac function and how
      interactions with AKAPs facilitate AC function, highlighting newly appreciated
      roles for lesser abundant AC isoforms.

PMID- 29367581
TI  - Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied
      in Portugal.
AB  - Pre-eclampsia and eclampsia are two hypertensive disorders of pregnancy,
      considered major causes of maternal and perinatal death worldwide. Pre-eclampsia
      is a multisystemic disease characterized by the development of hypertension after
      20 weeks of gestation, with the presence of proteinuria or, in its absence, of
      signs or symptoms indicative of target organ injury. Eclampsia represents the
      consequence of brain injuries caused by pre-eclampsia. The correct diagnosis and
      classification of the disease are essential, since the therapies for the mild and
      severe forms of pre-eclampsia are different. Thus, this review aims to describe
      the most advisable antepartum pharmacotherapy for pre-eclampsia and eclampsia
      applied in Portugal and based on several national and international available
      guidelines. Slow-release nifedipine is the most recommended drug for mild pre
      eclampsia, and labetalol is the drug of choice for the severe form of the
      disease. Magnesium sulfate is used to prevent seizures caused by eclampsia.
      Corticosteroids are used for fetal lung maturation. Overall, the pharmacological
      prevention of these diseases is limited to low-dose aspirin, so it is important
      to establish the safest and most effective available treatment.

PMID- 29367585
TI  - A Case of Recurrent Pasteurella Bacteremia in an Immunocompetent Patient with No
      Animal Bite.
AB  - BACKGROUND Pasteurella multocida is a gram negative-penicillin sensitive
      bacterium and is part of normal respiratory microbiota of animals (e.g., cats and
      dogs) and some birds. Various infections in humans, such as cellulitis, rarely
      bacteremia, endocarditis, meningitis, and septic arthritis, are a result of
      domestic cat or dog bites. These infections are rarely seen in an immunocompetent
      person, without an associated animal bite. CASE REPORT We present a case of
      refractory Pasteurella multocida bacteremia without any animal bite in an
      immunocompetent person. CONCLUSIONS Pasteurella multocida bacteremia has been
      seen in immunocompromised patients and mostly after a cat or dog bite or scratch
      but might also happen in immunocompetent humans with only pet licking rather than
      biting, which might increase hospital and emergency department visits or
      admissions in the future.

PMID- 29367586
TI  - Neutrophil Gelatinase-Associated Lipocalin Attenuates Ischemia/Reperfusion Injury
      in an In Vitro Model via Autophagy Activation.
AB  - BACKGROUND The aim of this study was to investigate the protective effects of
      neutrophil gelatinase-associated lipocalin (NGAL) on hypoxia/reoxygenation (H/R)
      induced acute kidney injury (AKI) in vitro. MATERIAL AND METHODS We used NRK-52E
      cells and H/R treatments to mimic ischemia/reperfusion injury (IRI) in vitro.
      Experimental groups were: the control group, the H/R group, the 3-methyladenine
      (3-MA)+H/R group, the NGAL (0.25, 0.5, and 1 ug/mL)+H/R group, and the NGAL
      (0.25, 0.5, 1 ug/mL)+3-MA+H/R group. After 24 hours of culture, cell
      proliferation was analyzed by CCK-8 assay. Expression of LC3-II was detected by
      immunoblot assay. Autophagy was detected by electron microscopy. RESULTS The
      expression of LC3-II was increased in the H/R group compared with normoxic
      condition (p<0.05) and proliferation also improved. Autophagy was significantly
      inhibited by 3-MA, with downregulated of LC3-II, followed by decreased cell
      viability (p<0.05). We further detected the effect of different doses of NGAL in
      H/R induced injury, and found that low doses of NGAL alone slightly increased LC3
      II protein accumulation, and autophagy was further induced with higher dose of
      NGAL treatment. Meanwhile, cell viability assays showed induced cell survival. We
      found that in the NGAL+3-MA group, cell viability assays revealed reduced cell
      damage, followed concomitantly with depressed autophagy. The formulation of
      autophagosomes were correlated with LC3-II protein expression in each group.
      CONCLUSIONS Autophagy plays a renoprotective role in H/R injury, as well in AKI.
      NGAL might be related to attenuated tubular epithelial cell damage via adjusting
      autophagy.

PMID- 29367582
TI  - Imaging of PDE2- and PDE3-Mediated cGMP-to-cAMP Cross-Talk in Cardiomyocytes.
AB  - Cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic
      guanosine monophosphate (cGMP) are important second messengers that regulate
      cardiovascular function and disease by acting in discrete subcellular
      microdomains. Signaling compartmentation at these locations is often regulated by
      phosphodiesterases (PDEs). Some PDEs are also involved in the cross-talk between
      the two second messengers. The purpose of this review is to summarize and
      highlight recent findings about the role of PDE2 and PDE3 in cardiomyocyte cyclic
      nucleotide compartmentation and visualization of this process using live cell
      imaging techniques.

PMID- 29367587
TI  - Long non-coding RNA and microRNA-675/let-7a mediates the protective effect of
      melatonin against early brain injury after subarachnoid hemorrhage via targeting
      TP53 and neural growth factor.
AB  - The objective of this study was to identify the protective effect of melatonin
      (MT) against early brain injury (EBI) following subarachnoid hemorrhage (SAH) and
      explore the underlying molecular mechanism. Real-time polymerase chain reaction
      (PCR) and luciferase assay were utilized to detect the effect of MT on H19
      expression level, computation analysis and luciferase assay were conducted to the
      underlying mechanism of let-7a and miR-675. Real-time PCR, western blot analysis,
      immunohistochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay, and flow cytometry analysis were performed to detect the
      effect of MT on H19, miR-675, let-7a, TP53, neural growth factor (NGF) levels,
      cell viability, and apoptosis status. Melatonin increased H19 expression level by
      enhancing H19 transcriptional efficiency in a concentration-dependent manner. MiR
      675 and let-7a directly targeted P53 and NGF, respectively, and miR-675 reduced
      luciferase activity of wild-type but not mutant TP53 3'UTR. Meanwhile, let-7a
      suppressed luciferase activity of wild-type but not mutant NGF 3'UTR. H2O2
      increased number of SA-b-gal, and while MT administration repressed the premature
      senescence. H2O2 obviously upregulated expressions of H19, miR-675, and NGF, and
      downregulated let-7a and TP53 levels; however, MT treatment reduced expressions
      of H19, miR-675, and NGF, and improved let-7a and TP53 levels. Treating with MT
      attenuated the neurological deficits and reduced the brain swelling. MT treatment
      repressed apoptosis of neurons caused by SAH. Levels of H19, miR-675, and NGF
      were much higher in the SAH +  MT group, while there were even higher levels of
      H19, miR-675, and NGF in the SAH group than in the sham group; levels of let-7a
      and TP53 were much lower in the SAH + MT group, while they were even lower in the
      SAH group than in the sham group. Our study revealed that treatment with MT
      protected against EBI after SAH by modulating the signaling pathways of H19-miR
      675-P53-apoptosis and H19-let-7a-NGF-apoptosis.

PMID- 29367588
TI  - Dysfunctional autophagy following exposure to pro-inflammatory cytokines
      contributes to pancreatic beta-cell apoptosis.
AB  - Type 1 diabetes (T1D) results from beta-cell destruction due to concerted action
      of both innate and adaptive immune responses. Pro-inflammatory cytokines, such as
      interleukin-1beta and interferon-gamma, secreted by the immune cells invading
      islets of Langerhans, contribute to pancreatic beta-cell death in T1D. Cytokine
      induced endoplasmic reticulum (ER) stress plays a central role in beta-cell
      demise. ER stress can modulate autophagic response; however, no study addressed
      the regulation of autophagy during the pathophysiology of T1D. In this study, we
      document that cytokines activate the AMPK-ULK-1 pathway while inhibiting mTORC1,
      which stimulates autophagy activity in an ER stress-dependent manner. On the
      other hand, time-course analysis of LC3-II accumulation in autophagosomes
      revealed that cytokines block the autophagy flux in an ER stress independent
      manner, leading to the formation of large dysfunctional autophagosomes and
      worsening of ER stress. Cytokines rapidly impair lysosome function, leading to
      lysosome membrane permeabilization, Cathepsin B leakage and lysosomal cell death.
      Blocking cathepsin activity partially protects against cytokine-induced or torin1
      induced apoptosis, whereas blocking autophagy aggravates cytokine-induced CHOP
      overexpression and beta-cell apoptosis. In conclusion, cytokines stimulate the
      early steps of autophagy while blocking the autophagic flux, which aggravate ER
      stress and trigger lysosomal cell death. Restoration of autophagy/lysosomal
      function may represent a novel strategy to improve beta-cell resistance in the
      context of T1D.

PMID- 29367584
TI  - Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and
      Growth.
AB  - Cardiovascular disease (CVD), including myocardial infarction (MI) and peripheral
      or coronary artery disease (PAD, CAD), remains the number one killer of
      individuals in the United States and worldwide, accounting for nearly 18 million
      (>30%) global deaths annually. Despite considerable basic science and clinical
      investigation aimed at identifying key etiologic components of and potential
      therapeutic targets for CVD, the number of individuals afflicted with these
      dreaded diseases continues to rise. Of the many biochemical, molecular, and
      cellular elements and processes characterized to date that have potential to
      control foundational facets of CVD, the multifaceted cyclic nucleotide pathways
      continue to be of primary basic science and clinical interest. Cyclic adenosine
      monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) and
      their plethora of downstream protein kinase effectors serve ubiquitous roles not
      only in cardiovascular homeostasis but also in the pathogenesis of CVD. Already a
      major target for clinical pharmacotherapy for CVD as well as other pathologies,
      novel and potentially clinically appealing actions of cyclic nucleotides and
      their downstream targets are still being discovered. With this in mind, this
      review article focuses on our current state of knowledge of the cyclic nucleotide
      driven serine (Ser)/threonine (Thr) protein kinases in CVD with particular
      emphasis on cyclic AMP-dependent protein kinase (PKA) and cyclic GMP-dependent
      protein kinase (PKG). Attention is given to the regulatory interactions of these
      kinases with inflammatory components including interleukin 6 signals, with G
      protein-coupled receptor and growth factor signals, and with growth and synthetic
      transcriptional platforms underlying CVD pathogenesis. This article concludes
      with a brief discussion of potential future directions and highlights the
      importance for continued basic science and clinical study of cyclic nucleotide
      directed protein kinases as emerging and crucial controllers of cardiac and
      vascular disease pathologies.

PMID- 29367590
TI  - Whole-genome assembly of the coral reef Pearlscale Pygmy Angelfish (Centropyge
      vrolikii).
AB  - The diversity of DNA sequencing methods and algorithms for genome assemblies
      presents scientists with a bewildering array of choices. Here, we construct and
      compare eight candidate assemblies combining overlapping shotgun read data, mate
      pair and Chicago libraries and four different genome assemblers to produce a high
      quality draft genome of the iconic coral reef Pearlscale Pygmy Angelfish,
      Centropyge vrolikii (family Pomacanthidae). The best candidate assembly combined
      all four data types and had a scaffold N50 127.5 times higher than the candidate
      assembly obtained from shotgun data only. Our best candidate assembly had a
      scaffold N50 of 8.97 Mb, contig N50 of 189,827, and 97.4% complete for BUSCO v2
      (Actinopterygii set) and 95.6% complete for CEGMA matches. These contiguity and
      accuracy scores are higher than those of any other fish assembly released to date
      that did not apply linkage map information, including those based on more
      expensive long-read sequencing data. Our analysis of how different data types
      improve assembly quality will help others choose the most appropriate de novo
      genome sequencing strategy based on resources and target applications.
      Furthermore, the draft genome of the Pearlscale Pygmy angelfish will play an
      important role in future studies of coral reef fish evolution, diversity and
      conservation.

PMID- 29367589
TI  - Evolutionary adaptations to new environments generally reverse plastic phenotypic
      changes.
AB  - Organismal adaptation to a new environment may start with plastic phenotypic
      changes followed by genetic changes, but whether the plastic changes are stepping
      stones to genetic adaptation is debated. Here we address this question by
      investigating gene expression and metabolic flux changes in the two-phase
      adaptation process using transcriptomic data from multiple experimental evolution
      studies and computational metabolic network analysis, respectively. We discover
      that genetic changes more frequently reverse than reinforce plastic phenotypic
      changes in virtually every adaptation. Metabolic network analysis reveals that,
      even in the presence of plasticity, organismal fitness drops after environmental
      shifts, but largely recovers through subsequent evolution. Such fitness
      trajectories explain why plastic phenotypic changes are genetically compensated
      rather than strengthened. In conclusion, although phenotypic plasticity may serve
      as an emergency response to a new environment that is necessary for survival, it
      does not generally facilitate genetic adaptation by bringing the organismal
      phenotype closer to the new optimum.

PMID- 29367591
TI  - Publisher Correction: Low dose nitrite improves reoxygenation following renal
      ischemia in rats.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29367593
TI  - Active microbial biofilms in deep poor porous continental subsurface rocks.
AB  - Deep continental subsurface is defined as oligotrophic environments where
      microorganisms present a very low metabolic rate. To date, due to the energetic
      cost of production and maintenance of biofilms, their existence has not been
      considered in poor porous subsurface rocks. We applied fluorescence in situ
      hybridization techniques and confocal laser scanning microscopy in samples from a
      continental deep drilling project to analyze the prokaryotic diversity and
      distribution and the possible existence of biofilms. Our results show the
      existence of natural microbial biofilms at all checked depths of the Iberian
      Pyrite Belt (IPB) subsurface and the co-occurrence of bacteria and archaea in
      this environment. This observation suggests that multi-species biofilms may be a
      common and widespread lifestyle in subsurface environments.

PMID- 29367592
TI  - Persistent activation of interlinked type 2 airway epithelial gene networks in
      sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics.
AB  - Atopic asthma is a persistent disease characterized by intermittent wheeze and
      progressive loss of lung function. The disease is thought to be driven primarily
      by chronic aeroallergen-induced type 2-associated inflammation. However, the vast
      majority of atopics do not develop asthma despite ongoing aeroallergen exposure,
      suggesting additional mechanisms operate in conjunction with type 2 immunity to
      drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells
      to identify gene networks operative at baseline in house dust mite-sensitized
      (HDMS) subjects with/without wheezing history that are characteristic of the
      ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was
      equivalent in both cohorts of subjects. However, in HDMS-wheezers they were
      associated with upregulation of two coexpression modules comprising multiple type
      2- and epithelial-associated genes. The first module was interlinked by the hubs
      EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and
      mucociliary clearance genes. Our findings provide new insight into the molecular
      mechanisms operative at baseline in the airway mucosa in atopic asthmatics
      undergoing natural aeroallergen exposure, and suggest that susceptibility to
      asthma amongst these subjects involves complex interactions between type 2- and
      epithelial-associated gene networks, which are not operative in equivalently
      sensitized/exposed atopic non-asthmatics.

PMID- 29367594
TI  - Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance
      in small cell lung cancer by sponging miR-216a.
AB  - Despite progress in treatment of small cell lung cancer (SCLC), its multidrug
      chemoresistance and poor prognosis still remain. Recently, we globally assessed
      long non-coding RNAs (lncRNAs) for contributions to SCLC chemoresistance using
      microarray data, in vitro and in vivo assays. Here we reported that HOTTIP,
      encoding a lncRNA that is frequently amplified in SCLC, was associated with SCLC
      cell chemosensitivity, proliferation, and poor prognosis of SCLC patients.
      Moreover, mechanistic investigations showed that HOTTIP functioned as an oncogene
      in SCLC progression by binding miR-216a and abrogating its tumor-suppressive
      function in this setting. On the other hand, HOTTIP increased the expression of
      anti-apoptotic factor BCL-2, another important target gene of miR-216a, and
      jointly enhanced chemoresistance of SCLC by regulating BCL-2. Taken together, our
      study established a role for HOTTIP in SCLC progression and chemoresistance
      suggest its candidacy as a new diagnostic and prognostic biomarker for clinical
      management of SCLC.

PMID- 29367595
TI  - New 2-Aryl-9-methyl-beta-carbolinium salts as Potential Acetylcholinesterase
      Inhibitor agents: Synthesis, Bioactivity and Structure-Activity Relationship.
AB  - A series of 2-aryl-9-methyl-beta-carbolinium bromides (B) were synthesized and
      explored for anti-acetylcholinesterase (AChE) activities in vitro, action
      mechanism and structure-activity relationship. All the compounds B along with
      their respective 3,4-dihydro intermediates (A) presented anti-AChE activity at 10
      MUM. Thirteen compounds B showed the excellent activity with IC50 values of 0.11
      0.76 MUM and high selectivity toward AChE relative to butyrylcholinesterase
      (BChE), superior to galantamine (IC50 = 0.79 MUM), a selective AChE inhibitor
      drug. Kinetic analysis showed that the action mechanisms of both compounds B and
      A are a competitive inhibition model. Structure-activity relationship analyses
      showed that the C = N+ moiety is a determinant for the activity. Substituents at
      6, 7 or 4' site, the indole-N-alkyl and the aromatization of the C-ring can
      significantly improve the activity. Molecular docking studies showed that the
      compounds could combine with the active site of AChE by the pi-pi or cation-pi
      action between the carboline ring and the phenyl rings of the residues, and the
      beta-carboline moiety is embedded in a cavity surrounded by four aromatic
      residues of Trp86, Tyr337, Trp439 and Tyr449. The present results strongly
      suggest that the para-position of the D-ring should be a preferred modification
      site for further structural optimization design. Thus, 2-aryl-9-methyl-beta
      carboliniums emerged as novel and promising tool compounds for the development of
      new AChE inhibitor agents.

PMID- 29367596
TI  - Graphene-based nonvolatile terahertz switch with asymmetric electrodes.
AB  - We propose a nonvolatile terahertz (THz) switch which is able to perform the
      switching with transient stimulus. The device utilizes graphene as its floating
      gate layer, which changes the transmissivity of THz signal by trapping the
      tunneling charges. The conventional top-down electrode configuration is replaced
      by a left-right electrode configuration, so THz signals could transmit through
      this device with the transmissivity being controlled by voltage pulses. The two
      electrodes are made of metals with different work functions. The resultant
      asymmetrical energy band structure ensures that both electrical programming and
      erasing are viable. With the aid of localized surface plasmon resonances in
      graphene ribbon arrays, the modulation depth is 89% provided that the Femi level
      of graphene is tuned between 0 and 0.2 eV by proper voltage pulses.

PMID- 29367597
TI  - Neuronal messenger ribonucleoprotein transport follows an aging Levy walk.
AB  - Localization of messenger ribonucleoproteins (mRNPs) plays an essential role in
      the regulation of gene expression for long-term memory formation and neuronal
      development. Knowledge concerning the nature of neuronal mRNP transport is thus
      crucial for understanding how mRNPs are delivered to their target synapses. Here,
      we report experimental and theoretical evidence that the active transport
      dynamics of neuronal mRNPs, which is distinct from the previously reported motor
      driven transport, follows an aging Levy walk. Such nonergodic, transient
      superdiffusion occurs because of two competing dynamic phases: the motor-involved
      ballistic run and static localization of mRNPs. Our proposed Levy walk model
      reproduces the experimentally extracted key dynamic characteristics of mRNPs with
      quantitative accuracy. Moreover, the aging status of mRNP particles in an
      experiment is inferred from the model. This study provides a predictive
      theoretical model for neuronal mRNP transport and offers insight into the active
      target search mechanism of mRNP particles in vivo.

PMID- 29367598
TI  - Cerebral Perfusion Insufficiency and Relationships with Cognitive Deficits in
      Alzheimer's Disease: A Multiparametric Neuroimaging Study.
AB  - Micro- or macro-circulatory insufficiency has a negative impact in patients with
      Alzheimer's disease (AD). This study used arterial spin-labeled magnetic
      resonance imaging (ASL-MRI) and ethylcysteinate dimer single-photon emission
      computed tomography (ECD-SPECT) in 50 patients with AD and 30 age-matched
      controls to investigate how hypoperfusion patterns were associated with gray
      matter atrophy and clinical data. All participants completed 3DT1-MRI, ECD-SPECT
      and ASL-MRI examinations. Medial temporal cortex (MTC) volumes were correlated
      with regional signals showing significantly lower relative cerebral blood flow
      (rCBF) in ASL-MRI or perfusion index (PI) in ECD-SPECT. Neurobehavioral scores
      served as the outcome measures. Regions with lower PI showed spatial similarities
      with atrophy in the medial, anterior and superior temporal lobes, posterior
      cingulate cortex and angular gyrus, while regions showing lower rCBF were
      localized to the distal branches of posterior cerebral artery territories
      (posterior parietal and inferior temporal lobe) and watershed areas (angular
      gyrus, precuneus, posterior cingulate gyrus and middle frontal cortex). rCBF
      values in watershed areas correlated with MTC volumes and language composite
      scores. Precuneus and angular gyrus hypoperfusion were associated with the
      corresponding cortical atrophy. Macro- or micro-vasculature perfusion integrities
      and cortical atrophy determined the overall perfusion imaging topography and
      contributed differently to the clinical outcomes.

PMID- 29367599
TI  - Coupling molecular data and experimental crosses sheds light about species
      delineation: a case study with the genus Ciona.
AB  - Molecular studies sometimes reveal evolutionary divergence within accepted
      species. Such findings can initiate taxonomic revision, as exemplified in the
      formerly recognized species Ciona intestinalis. While an increasing number of
      studies have examined the ecology, reproductive barriers and genetics of C.
      intestinalis and C. robusta, there are still much uncertainties regarding other
      species of this genus. Using experimental crosses and mitochondrial data, we
      investigated the evolutionary relationships among four native and introduced
      Ciona spp., found in sympatry in the Mediterranean Sea or English Channel.
      Outcome of 62 bi-parental reciprocal crosses between C. intestinalis, C. robusta,
      C. roulei and C. edwardsi showed that C. edwardsi is reproductively isolated from
      the other taxa, which is in agreement with its distinct location in the
      phylogenetic tree. Conversely, hybrids are easily obtained in both direction when
      crossing C. intestinalis and C. roulei, reinforcing the hypothesis of two
      genetically differentiated lineages but likely being from a same species.
      Altogether, this study sheds light on the evolutionary relationship in this
      complex genus. It also calls for further investigation notably based on genome
      wide investigation to better describe the evolutionary history within the genus
      Ciona, a challenging task in a changing world where biological introductions are
      shuffling species distribution.

PMID- 29367600
TI  - Transmembrane protein 170B is a novel breast tumorigenesis suppressor gene that
      inhibits the Wnt/beta-catenin pathway.
AB  - The identification of specific drug targets guides the development of precise
      cancer treatments. Compared with oncogenes, tumor suppressor genes have been
      poorly studied in the treatment of breast cancer. We integrate the microRNA
      expression array from GEO (Gene Expression Omnibus) and TCGA (The Cancer Genome
      Atlas) databases in clinical breast cancer tissues, and find that miR-27a is
      significantly upregulated and correlated with poor survival outcome and tumor
      progression. Transmembrane protein 170B (TMEM170B), a new functional target of
      miR-27a, is identified via target prediction and experimental validation,
      suppressing breast cancer proliferation, metastasis, and tumorigenesis.
      Furthermore, TMEM170B overexpression promotes cytoplasmic beta-catenin
      phosphorylation, resulting in the inhibition of beta-catenin stabilization,
      reduction of nuclear beta-catenin levels and downstream targets expression.
      Clinically, TMEM170B or beta-catenin expression is significantly correlated with
      overall survival ratio in breast cancer patients. Thus, these results highlight
      TMEM170B as a novel tumor suppressor target in association with the beta-catenin
      pathway, which may provide a new therapeutic approach for human breast cancer
      therapy.

PMID- 29367601
TI  - Environmental pH modulates inerolysin activity via post-binding blockade.
AB  - The cholesterol dependent cytolysins (CDCs) are a family of pore-forming toxins
      produced by a wide range of bacteria. Some CDCs are important virulence factors
      for their cognate organisms, but their activity must be tightly regulated to
      ensure they operate at appropriate times and within the appropriate subcellular
      compartments. pH-dependent activity has been described for several CDCs, but the
      mechanism of such regulation has been studied in depth only for listeriolysin O
      (LLO), which senses environmental pH through a triad of acidic residues that
      mediate protein unfolding. Here we present data supporting a distinct mechanism
      for pH-dependence for inerolysin (INY), the CDC produced by Lactobacillus iners.
      Inerolysin (INY) has an acidic pH optimum with loss of activity at neutral pH.
      INY pH-dependence is characterized by reversible loss of pore formation with
      preservation of membrane binding. Fluorescent membrane probe assays indicated
      that INY insertion into host cell membranes, but not oligomerization, was
      defective at neutral pH. These data support the existence of a newly appreciated
      form of CDC pH-dependence functioning at a late stage of pore formation.

PMID- 29367602
TI  - Regulation of REM and Non-REM Sleep by Periaqueductal GABAergic Neurons.
AB  - Mammalian sleep consists of distinct rapid eye movement (REM) and non-REM (NREM)
      states. The midbrain region ventrolateral periaqueductal gray (vlPAG) is known to
      be important for gating REM sleep, but the underlying neuronal mechanism is not
      well understood. Here, we show that activating vlPAG GABAergic neurons in mice
      suppresses the initiation and maintenance of REM sleep while consolidating NREM
      sleep, partly through their projection to the dorsolateral pons. Cell-type
      specific recording and calcium imaging reveal that most vlPAG GABAergic neurons
      are strongly suppressed at REM sleep onset and activated at its termination. In
      addition to the rapid changes at brain state transitions, their activity
      decreases gradually between REM sleep and is reset by each REM episode in a
      duration-dependent manner, mirroring the accumulation and dissipation of REM
      sleep pressure. Thus, vlPAG GABAergic neurons powerfully gate REM sleep, and
      their firing rate modulation may contribute to the ultradian rhythm of REM/NREM
      alternation.

PMID- 29367603
TI  - Multifunctional viral protein gamma34.5 manipulates nucleolar protein NOP53 for
      optimal viral replication of HSV-1.
AB  - To ensure efficient virus replication, herpes simplex virus type 1 (HSV-1)
      encodes several viral proteins to counter host defense response upon infection.
      Among these proteins, the multifunctional viral protein gamma34.5 crucially
      interferes with or disrupts several antiviral pathways at multiple levels. The
      current study shows that gamma34.5 utilizes nucleolar protein NOP53 to facilitate
      the dephosphorylation of eukaryotic initiation factor eIF2alpha for efficient
      viral translation. Our study shows that: (1) ectopic expression of NOP53 greatly
      increases the intracellular and extracellular viral yields of HSV-1 (wild strain
      F) in type I interferon-deficient Vero cells, and more subtly promotes viral
      replication of gamma34.5 deletion mutant virus HSV-1/Deltagamma34.5. (2) NOP53 is
      migrated from nuclei in HSV-1/F infected cells, but is redistributed incompletely
      after infection by either HSV-1/Deltagamma34.5 or ICP4 deletion mutant virus HSV
      1/d120 (replication inadequate). Ectopic expression of gamma34.5, consequently,
      induces cytoplasmic translocation of NOP53 in response to HSV-1/Deltagamma34.5
      infection. (3) Increase of NOP53, in two forms of transient transfection and in
      vitro expression, attenuates the phosphorylation level of eIF2alpha in HSV-1/F
      infected cells, but fails to affect eIF2alpha phosphorylation induced by HSV
      1/Deltagamma34.5 infection. (4) Knockdown of NOP53, which impairs the specific
      interaction between gamma34.5 and protein phosphatase PP1alpha, disrupts the
      ability of gamma34.5 to maintain HSV-1 virulence. (5) NOP53 knockdown also
      significantly reduces tissue damage and decreases viral yield in livers of HSV-1
      infected mice. Our findings expand the understanding of the underlying mechanism
      by which viral protein gamma34.5 induces NOP53 redistribution; cytoplasmic NOP53
      facilitates gamma34.5 recruitment of PP1alpha to dephosphorylate eIF2alpha, for
      optimal viral replication. This paper also demonstrates that blocking the
      specific interaction between gamma34.5 and PP1alpha would be a useful approach
      for the development of antiviral agents.

PMID- 29367604
TI  - Covalent ISG15 conjugation to CHIP promotes its ubiquitin E3 ligase activity and
      inhibits lung cancer cell growth in response to type I interferon.
AB  - The carboxyl terminus of Hsp70-interacting protein (CHIP) acts as a ubiquitin E3
      ligase and a link between the chaperones Hsp70/90 and the proteasome system,
      playing a vital role in maintaining protein homeostasis. CHIP regulates a number
      of proteins involved in a myriad of physiological and pathological processes, but
      the underlying mechanism of action via posttranslational modification has not
      been extensively explored. In this study, we investigated a novel modulatory mode
      of CHIP and its effect on CHIP enzymatic activity. ISG15, an ubiquitin-like
      modifier, is induced by type I interferon (IFN) stimulation and can be conjugated
      to target proteins (ISGylation). Here we demonstrated that CHIP may be a novel
      target of ISGylation in HEK293 cells stimulated with type I IFN. We also found
      that Lys143/144/145 and Lys287 residues in CHIP are important for and target
      residues of ISGylation. Moreover, ISGylation promotes the E3 ubiquitin ligase
      activity of CHIP, subsequently causing a decrease in levels of oncogenic c-Myc,
      one of its many ubiquitination targets, in A549 lung cancer cells and inhibiting
      A549 cell and tumor growth. In conclusion, the present study demonstrates that
      covalent ISG15 conjugation produces a novel CHIP regulatory mode that enhances
      the tumor-suppressive activity of CHIP, thereby contributing to the antitumor
      effect of type I IFN.

PMID- 29367605
TI  - Single-cell variability in multicellular organisms.
AB  - Noisy gene expression is of fundamental importance to single cells, and is
      therefore widely studied in single-celled organisms. Extending these studies to
      multicellular organisms is challenging since their cells are generally not
      isolated, but individuals in a tissue. Cell-cell coupling via signalling, active
      transport or pure diffusion, ensures that tissue-bound cells are neither fully
      independent of each other, nor an entirely homogeneous population. In this
      article, we show that increasing the strength of coupling between cells can
      either increase or decrease the single-cell variability (and, therefore, the
      heterogeneity of the tissue), depending on the statistical properties of the
      underlying genetic network. We confirm these predictions using spatial stochastic
      simulations of simple genetic networks, and experimental data from animal and
      plant tissues. The results suggest that cell-cell coupling may be one of several
      noise-control strategies employed by multicellular organisms, and highlight the
      need for a deeper understanding of multicellular behaviour.

PMID- 29367606
TI  - Bacterial community in naturally fermented milk products of Arunachal Pradesh and
      Sikkim of India analysed by high-throughput amplicon sequencing.
AB  - Naturally fermented milk (NFM) products are popular ethnic fermented foods in
      Arunachal Pradesh and Sikkim states of India. The present study is the first to
      have documented the bacterial community in 54 samples of NFM products viz.
      chhurpi, churkam, dahi and gheu/mar by high-throughput Illumina amplicon
      sequencing. Metagenomic investigation showed that Firmicutes (Streptococcaceae,
      Lactobacillaceae) and Proteobacteria (Acetobacteraceae) were the two predominant
      members of the bacterial communities in these products. Lactococcus lactis and
      Lactobacillus helveticus were the predominant lactic acid bacteria while
      Acetobacter spp. and Gluconobacter spp. were the predominant acetic acid bacteria
      present in these products.

PMID- 29367607
TI  - Shielding and activation of a viral membrane fusion protein.
AB  - Entry of enveloped viruses relies on insertion of hydrophobic residues of the
      viral fusion protein into the host cell membrane. However, the intermediate
      conformations during fusion remain unknown. Here, we address the fusion mechanism
      of Rift Valley fever virus. We determine the crystal structure of the Gn
      glycoprotein and fit it with the Gc fusion protein into cryo-electron microscopy
      reconstructions of the virion. Our analysis reveals how the Gn shields the
      hydrophobic fusion loops of the Gc, preventing premature fusion. Electron
      cryotomography of virions interacting with membranes under acidic conditions
      reveals how the fusogenic Gc is activated upon removal of the Gn shield.
      Repositioning of the Gn allows extension of Gc and insertion of fusion loops in
      the outer leaflet of the target membrane. These data show early structural
      transitions that enveloped viruses undergo during host cell entry and indicate
      that analogous shielding mechanisms are utilized across diverse virus families.

PMID- 29367609
TI  - Flexibly tunable high-quality-factor induced transparency in plasmonic systems.
AB  - The quality (Q) factor and tunability of electromagnetically induced transparency
      (EIT)-like effect in plasmonic systems are restrained by the intrinsic loss and
      weak adjustability of metals, limiting the performance of the devices including
      optical sensor and storage. Exploring new schemes to realize the high Q-factor
      and tunable EIT-like effect is particularly significant in plasmonic systems.
      Here, we present an ultrahigh Q-factor and flexibly tunable EIT-like response in
      a novel plasmonic system. The results illustrate that the induced transparency
      distinctly appears when surface plasmon polaritons excited on the metal satisfy
      the wavevector matching condition with the guided mode in the high-refractive
      index (HRI) layer. The Q factor of the EIT-like spectrum can exceed 2000, which
      is remarkable compared to that of other plasmonic systems such as plasmonic
      metamaterials and waveguides. The position and lineshape of EIT-like spectrum are
      strongly dependent on the geometrical parameters. An EIT pair is generated in the
      splitting absorption spectra, which can be easily controlled by adjusting the
      incident angle of light. Especially, we achieve the dynamical tunability of EIT
      like spectrum by changing the Fermi level of graphene inserted in the system. Our
      results will open a new avenue toward the plasmonic sensing, spectral shaping and
      switching.

PMID- 29367608
TI  - An optimised protocol for platelet-rich plasma preparation to improve its
      angiogenic and regenerative properties.
AB  - Although platelet-rich plasma (PRP) is used as a source of growth factors in
      regenerative medicine, its effectiveness remains controversial, partially due to
      the absence of PRP preparation protocols based on the regenerative role of
      platelets. Here, we aimed to optimise the protocol by analysing PRP angiogenic
      and regenerative properties. Three optimising strategies were evaluated:
      dilution, 4  degrees C pre-incubation, and plasma cryoprecipitate
      supplementation. Following coagulation, PRP releasates (PRPr) were used to induce
      angiogenesis in vitro (HMEC-1 proliferation, migration, and tubule formation) and
      in vivo (chorioallantoic membrane), as well as regeneration of excisional wounds
      on mouse skin. Washed platelet releasates induced greater angiogenesis than PRPr
      due to the anti-angiogenic effect of plasma, which was decreased by diluting PRPr
      with saline. Angiogenesis was also improved by both PRP pre-incubation at 4 
      degrees C and cryoprecipitate supplementation. A combination of optimising
      variables exerted an additive effect, thereby increasing the angiogenic activity
      of PRPr from healthy donors and diabetic patients. Optimised PRPr induced faster
      and more efficient mouse skin wound repair compared to that induced by non
      optimised PRPr. Acetylsalicylic acid inhibited angiogenesis and tissue
      regeneration mediated by PRPr; this inhibition was reversed following
      optimisation. Our findings indicate that PRP pre-incubation at 4  degrees C, PRPr
      dilution, and cryoprecipitate supplementation improve the angiogenic and
      regenerative properties of PRP compared to the obtained by current methods.

PMID- 29367610
TI  - Removal of prolyl oligopeptidase reduces alpha-synuclein toxicity in cells and in
      vivo.
AB  - Prolyl oligopeptidase (PREP) inhibition by small-molecule inhibitors can reduce
      alpha-synuclein (aSyn) aggregation, a key player in Parkinson's disease
      pathology. However, the significance of PREP protein for aSyn aggregation and
      toxicity is not known. We studied this in vivo by using PREP knock-out mice with
      viral vector injections of aSyn and PREP. Animal behavior was studied by
      locomotor activity and cylinder tests, microdialysis and HPLC were used to
      analyze dopamine levels, and different aSyn forms and loss of dopaminergic
      neurons were studied by immunostainings. Additionally, PREP knock-out cells were
      used to characterize the impact of PREP and aSyn on autophagy, proteasomal system
      and aSyn secretion. PREP knock-out animals were nonresponsive to aSyn-induced
      unilateral toxicity but combination of PREP and aSyn injections increased aSyn
      toxicity. Phosphorylated p129, proteinase K resistant aSyn levels and tyrosine
      hydroxylase positive cells were decreased in aSyn and PREP injected knock-out
      animals. These changes were accompanied by altered dopamine metabolite levels.
      PREP knock-out cells showed reduced response to aSyn, while cells were restored
      to wild-type cell levels after PREP overexpression. Taken together, our data
      suggests that PREP can enhance aSyn toxicity in vivo.

PMID- 29367612
TI  - Use of whole genome sequencing to investigate an increase in Neisseria
      gonorrhoeae infection among women in urban areas of Australia.
AB  - Increasing rates of gonorrhoea have been observed among women within the
      Australian state of New South Wales. Here, we applied whole genome sequencing
      (WGS) to better understand the associated networks and transmission dynamics.
      Ninety-four isolates of a particular N. gonorrhoeae genotype (G122) associated
      with women (years 2012 to 2014) underwent phylogenetic analysis using core single
      nucleotide polymorphisms. WGS data revealed five main clusters, all of which were
      heterogeneous in terms of patient age and site of infection. The relatively high
      cervical/vaginal infections in each cluster was indicative of transmission in the
      general heterosexual population, noting that there is typically high rates of
      condom use for vaginal sex among local commercial sex workers. WGS also enabled
      the identification of groups of individuals belonging to tighter transmission
      chains within clusters, and hence may present a new tool for targeting public
      health interventions. The enhanced resolution of WGS provides a ready means of
      confirming suspected changes in N. gonorrhoeae epidemiology, but also enables key
      features to be identified or new questions to be raised regarding the composition
      of the associated sexual networks.

PMID- 29367611
TI  - Genome-wide association study of paclitaxel and carboplatin disposition in women
      with epithelial ovarian cancer.
AB  - Identifying single nucleotide polymorphisms (SNPs) that influence chemotherapy
      disposition may help to personalize cancer treatment and limit toxicity. Genome
      wide approaches are unbiased, compared with candidate gene studies, but usually
      require large cohorts. As most chemotherapy is given cyclically multiple blood
      sampling is required to adequately define drug disposition, limiting patient
      recruitment. We found that carboplatin and paclitaxel disposition are stable
      phenotypes in ovarian cancer patients and tested a genome-wide association study
      (GWAS) design to identify SNPs associated with chemotherapy disposition. We found
      highly significant SNPs in ABCC2, a known carboplatin transporter, associated
      with carboplatin clearance (asymptotic P = 5.2 * 106, empirical P = 1.4 * 10-5),
      indicating biological plausibility. We also identified novel SNPs associated with
      paclitaxel disposition, including rs17130142 with genome-wide significance
      (asymptotic P = 2.0 * 10-9, empirical P = 1.3 * 10-7). Although requiring further
      validation, our work demonstrated that GWAS of chemotherapeutic drug disposition
      can be effective, even in relatively small cohorts, and can be adopted in drug
      development and treatment programs.

PMID- 29367613
TI  - Integrating transient cellular and nuclear motions to comprehensively describe
      cell migration patterns.
AB  - Various subcellular activities, such as protrusion and detachment, compose a cell
      migration process. The molecular mechanisms of these subcellular activities have
      been elucidated. However, there is no method that can assess the contributions of
      these subcellular activities to the global cell migration pattern of a given cell
      type. Hence, we develop a powerful approach based on CN correlations that
      quantitatively profiles the cell migration pattern of a given cell type in terms
      of assembled subcellular activities. In this way, we bridge migration data at the
      cellular level with underlying molecular mechanisms. The CN correlation profile
      is found to uniquely and consistently represent the cell migration pattern of
      each cell type probed. It can clearly reveal the effects of molecular
      perturbations, such as Y27632 and Cdc42 knockdown on each subcellular migratory
      activity. As a result, the CN correlation approach serves as a cell dynamic
      descriptor that can extract comprehensive quantitative data from cell migration
      movies for integrative biological analyses.

PMID- 29367614
TI  - Central and cerebral haemodynamic changes after antihypertensive therapy in
      ischaemic stroke patients: A double-blind randomised trial.
AB  - Central and cerebral haemodynamic parameters can vary under similar brachial
      blood pressure (BP). We aimed to investigate the effects of antihypertensive
      agents on central and cerebral haemodynamic parameters in hypertensive patients
      with ischaemic stroke. The Fimasartan, Atenolol, and Valsartan On haemodynamic
      paRameters (FAVOR) study was conducted in a prospective, double-blinded manner.
      One hundred five patients were randomly administered atenolol, valsartan, or
      fimasartan during 12 weeks. We measured brachial, central, cerebral haemodynamic
      parameters and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels
      at baseline and after 12-week. Baseline haemodynamic parameters were balanced
      among the three groups. Even with similar brachial BP reduction, significantly
      lower central systolic BP (atenolol; 146.5 +/- 18.8 vs. valsartan; 133.5 +/- 20.7
      vs. fimasartan; 133.6 +/- 19.8 mmHg, p = 0.017) and augmentation index values
      (89.8 +/- 13.2 vs. 80.6 +/- 9.2 vs. 79.2 +/- 11.6%; p = 0.001) were seen in the
      angiotensin receptor blockers (ARBs) groups. The pulsatility index on
      transcranial Doppler was significantly reduced in valsartan (p = 0.002) and
      fimasartan group (p = 0.008). Plasma NT-proBNP level was also significantly
      decreased in ARB groups, especially for the fimasartan group (37.8 +/- 50.6 vs.
      29.2 +/- 36.9 vs.19.2 +/- 27.8 pg/mL; p = 0.006). These findings suggest that
      short-term ARB administration would be favourable for ischaemic stroke patients
      with hypertension, permitting effective reduction of central pressure and
      dampening of cerebral pulsatility.

PMID- 29367615
TI  - MicroRNA-379-5p is associate with biochemical premature ovarian insufficiency
      through PARP1 and XRCC6.
AB  - Premature ovarian insufficiency (POI) imposes great challenges on women's
      fertility and lifelong health. POI is highly heterogeneous and encompasses
      occult, biochemical, and overt stages. MicroRNAs (miRNAs) are negative regulators
      of gene expression, whose roles in physiology and diseases like cancers and
      neurological disorders have been recognized, but little is known about the miRNAs
      profile and functional relevance in biochemical POI (bPOI). In this study, the
      expression of miRNAs and mRNAs in granulosa cells (GCs) of bPOI women was
      determined by two microarrays, respectively. MiR-379-5p, PARP1, and XRCC6 were
      differentially expressed in GCs of bPOI as revealed by microarrays. Subsequently,
      functional studies demonstrated that miR-379-5p overexpression inhibited
      granulosa cell proliferation and attenuated DNA repair efficiency. Furthermore,
      both PARP1 and XRCC6 showed lower levels in GCs from patients with bPOI and were
      identified as executives of miR-379-5p. Therefore, our data first uncovered
      potentially pathogenic miR-379-5p and two novel targets PARP1 and XRCC6 in bPOI,
      which corroborated the significance of DNA repair for POI, and brought up an
      epigenetic explanation for the disease.

PMID- 29367616
TI  - Single Plasmonic Structure Enhanced Dual-band Room Temperature Infrared
      Photodetection.
AB  - Dual-band photodetection in mid- and near-wave infrared spectral bands is of
      scientific interest and technological importance. Most of the state-of-the-art
      mid-infrared photodetectors normally operate at low temperature and/or suffer
      from toxicity and high cost due to limitations of material properties and device
      structures. The capability of surface plasmons in confining electromagnetic waves
      into extremely small volume provides an opportunity for improving the performance
      for room temperature operation. Here, we report an n-InAsSb/n-GaSb
      heterostructure photodiode integrated with plasmonic two-dimensional
      subwavelength hole array (2DSHA) for room temperature two band photodetection. We
      demonstrate that with a properly designed 2DSHA, room temperature detectivities
      of the heterostructure device can be enhanced to ~1.4 * 109 Jones and ~1.5 * 1011
      Jones for the two bands peaked at 3.4 MUm and 1.7 MUm, respectively. In addition,
      we study the photocurrent enhancement in both photoconductor and heterojunction
      modes in the same integrated structure. The demonstration of single 2DSHA
      enhanced heterojunction photodiode brings a step closer to high sensitivity room
      temperature devices and systems which require multiband absorption.

PMID- 29367617
TI  - Genome-wide association mapping and genomic prediction for CBSD resistance in
      Manihot esculenta.
AB  - Cassava (Manihot esculenta Crantz) is an important security crop that faces
      severe yield loses due to cassava brown streak disease (CBSD). Motivated by the
      slow progress of conventional breeding, genetic improvement of cassava is
      undergoing rapid change due to the implementation of quantitative trait loci
      mapping, Genome-wide association mapping (GWAS), and genomic selection (GS). In
      this study, two breeding panels were genotyped for SNP markers using genotyping
      by sequencing and phenotyped for foliar and CBSD root symptoms at five locations
      in Uganda. Our GWAS study found two regions associated to CBSD, one on chromosome
      4 which co-localizes with a Manihot glaziovii introgression segment and one on
      chromosome 11, which contains a cluster of nucleotide-binding site-leucine-rich
      repeat (NBS-LRR) genes. We evaluated the potential of GS to improve CBSD
      resistance by assessing the accuracy of seven prediction models. Predictive
      accuracy values varied between CBSD foliar severity traits at 3 months after
      planting (MAP) (0.27-0.32), 6 MAP (0.40-0.42) and root severity (0.31-0.42). For
      all traits, Random Forest and reproducing kernel Hilbert spaces regression showed
      the highest predictive accuracies. Our results provide an insight into the
      genetics of CBSD resistance to guide CBSD marker-assisted breeding and highlight
      the potential of GS to improve cassava breeding.

PMID- 29367618
TI  - Prohibitin 2 localizes in nucleolus to regulate ribosomal RNA transcription and
      facilitate cell proliferation in RD cells.
AB  - Prohibitin 2 (PHB2), as a conserved multifunctional protein, is traditionally
      localized in the mitochondrial inner membrane and essential for maintenance of
      mitochondrial function. Here, we investigated the role of PHB2 in human
      rhabdomyosarcoma (RMS) RD cells and found substantial localization of PHB2 in the
      nucleolus. We demonstrated that PHB2 knockdown inhibited RD cell proliferation
      through inducing cell cycle arrest and suppressing DNA synthesis. Meanwhile, down
      regulation of PHB2 also induced apoptosis and promoted differentiation in
      fractions of RD cells. In addition, PHB2 silencing led to altered nucleolar
      morphology, as observed by transmission electron microscopy, and impaired
      nucleolar function, as evidenced by down-regulation of 45S and 18S ribosomal RNA
      synthesis. Consistently, upon PHB2 knockdown, occupancy of c-Myc at the ribosomal
      DNA (rDNA) promoter was attenuated, while more myoblast determination protein 1
      (MyoD) molecules bound to the rDNA promoter. In conclusion, our findings suggest
      that nucleolar PHB2 is involved in maintaining nucleolar morphology and function
      in RD cells by regulating a variety of transcription factors, which is likely to
      be one of the underlying mechanisms by which PHB2 promotes tumor proliferation
      and represses differentiation. Our study provides new insight into the
      pathogenesis of RMS and novel characterizations of the highly conserved PHB2
      protein.

PMID- 29367619
TI  - Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel
      disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of
      inflammatory bowel disease (IBD) patients, often in absence of metabolic risk
      factors. Nevertheless, most of previous studies on such issue were conducted
      within the IBD population only. The primary aim of this study was to compare
      clinical and metabolic features of NAFLD in patients with and without IBD (w/o
      IBD) and to identify specific NAFLD phenotypes within the IBD population. Among
      223 NAFLD patients, 78 patients with IBD were younger compared to 145 without
      (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body
      weight, smaller waist circumference and lower body mass index (BMI); at the same
      time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001).
      Within IBD population, patients with severe IBD showed more often severe
      steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to
      moderate disease. Independent risk factors for S3 US steatosis in IBD patients at
      the multivariate logistic regression analysis were: more than 1 IBD relapse per
      year during disease history (OR 17.3, 95% CI 3.6-84), surgery for IBD (OR 15.1,
      95% CI 3.1-73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4
      110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFalpha) therapy was
      the only independent factor which protect toward the presence of altered liver
      enzymes (OR 0.15, 95% CI 0-0.8, p = 0.02). In conclusion, NAFLD in IBD patients
      is different from that in patients w/o IBD, who seem to develop different NAFLD
      phenotypes according to intestinal disease clinical course. More severe IBD seem
      to predict the presence of more severe steatosis. Therapy with antiTNFalpha
      antibodies could prevent alteration of liver enzymes in such population.

PMID- 29367620
TI  - Vital Recorder-a free research tool for automatic recording of high-resolution
      time-synchronised physiological data from multiple anaesthesia devices.
AB  - The current anaesthesia information management system (AIMS) has limited
      capability for the acquisition of high-quality vital signs data. We have
      developed a Vital Recorder program to overcome the disadvantages of AIMS and to
      support research. Physiological data of surgical patients were collected from 10
      operating rooms using the Vital Recorder. The basic equipment used were a patient
      monitor, the anaesthesia machine, and the bispectral index (BIS) monitor.
      Infusion pumps, cardiac output monitors, regional oximeter, and rapid infusion
      device were added as required. The automatic recording option was used
      exclusively and the status of recording was frequently checked through web
      monitoring. Automatic recording was successful in 98.5% (4,272/4,335) cases
      during eight months of operation. The total recorded time was 13,489 h (3.2 +/-
      1.9 h/case). The Vital Recorder's automatic recording and remote monitoring
      capabilities enabled us to record physiological big data with minimal effort. The
      Vital Recorder also provided time-synchronised data captured from a variety of
      devices to facilitate an integrated analysis of vital signs data. The free
      distribution of the Vital Recorder is expected to improve data access for
      researchers attempting physiological data studies and to eliminate inequalities
      in research opportunities due to differences in data collection capabilities.

PMID- 29367622
TI  - Cell-in-cell phenomena, cannibalism, and autophagy: is there a relationship?

PMID- 29367621
TI  - Optineurin-mediated mitophagy protects renal tubular epithelial cells against
      accelerated senescence in diabetic nephropathy.
AB  - Premature senescence is a key process in the progression of diabetic nephropathy
      (DN). Premature senescence of renal tubular epithelial cells (RTEC) in DN may
      result from the accumulation of damaged mitochondria. Mitophagy is the principal
      process that eliminates damaged mitochondria through PTEN-induced putative kinase
      1 (PINK1)-mediated recruitment of optineurin (OPTN) to mitochondria. We aimed to
      examine the involvement of OPTN in mitophagy regulation of cellular senescence in
      RTEC in the context of DN. In vitro, the expression of senescence markers P16,
      P21, DcR2, SA-beta-gal, SAHF, and insufficient mitophagic degradation marker
      (mitochondrial P62) in mouse RTECs increased after culture in 30 mM high-glucose
      (HG) conditions for 48 h. Mitochondrial fission/mitophagy inhibitor Mdivi-1
      significantly enhanced RTEC senescence under HG conditions, whereas
      autophagy/mitophagy agonist Torin1 inhibited cell senescence. MitoTempo inhibited
      HG-induced mitochondrial reactive oxygen species and cell senescence with or
      without Mdivi-1. The expression of PINK1 and OPTN, two regulatory factors for
      mitophagosome formation, decreased significantly after HG stimulation.
      Overexpression of PINK1 did not enhance mitophagosome formation under HG
      conditions. OPTN silencing significantly inhibited HG-induced mitophagosome
      formation, and overexpression of OPTN relieved cellular senescence through
      promoting mitophagy. In clinical specimens, renal OPTN expression was gradually
      decreased with increased tubulointerstitial injury scores. OPTN-positive renal
      tubular cells did not express senescence marker P16. OPTN expression also
      negatively correlated with serum creatinine levels, and positively correlated
      with eGFR. Thus, OPTN-mediated mitophagy plays a crucial regulatory role in HG
      induced RTEC senescence in DN. OPTN may, therefore, be a potential antisenescence
      factor in DN.

PMID- 29367623
TI  - Facile storage and release of white phosphorus and yellow arsenic.
AB  - The storage of metastable compounds and modifications of elements are of great
      interest for synthesis and other, e.g., semiconductor, applications. Whereas
      white phosphorus is a metastable modification that can be stored under certain
      conditions, storage of the extremely (light- and air-)sensitive form of arsenic,
      yellow arsenic, is a challenge rarely tackled so far. Herein, we report on the
      facile storage and release of these tetrahedral E4 molecules (E = P, As) using
      activated carbon as a porous storage material. These loaded materials are air-
      and light-stable and have been comprehensively characterized by solid-state
      31P{1H} MAS NMR spectroscopy, powder X-ray diffraction analysis, nitrogen
      adsorption measurements, and thermogravimetric analysis. Additionally, we show
      that these materials can be used as a suitable E4 source for releasing intact
      white phosphorus or yellow arsenic, enabling subsequent reactions in solution.
      Because the uptake and release of E4 are reversible, these materials are
      excellent carriers of these highly reactive modifications.

PMID- 29367625
TI  - Ring-Size Effects on the Stability and Spectral Shifts of Hydrogen Bonded Cyclic
      Ethers Complexes.
AB  - In order to investigate ring-size effects on the stability and spectral shifts of
      hydrogen bonded cyclic ethers complexes, the strength of hydrogen bonds in gas
      phase complexes formed between 2,2,2-trifluoroethanol (TFE) and selected cyclic
      ethers were examined using FTIR spectroscopy. TFE was chosen as hydrogen bond
      donor in these complexes, while trimethylene oxide (TMO), tetrahydrofuran (THF)
      and tetrahydropyran (THP) were selected as hydrogen bond acceptors. Comparable OH
      stretching red shifts were observed in the three kinds of complexes. The
      difference of red shifts is so small (<7 cm-1) for TFE-TMO/THF/THP complexes that
      one can conclude that their stabilities and the strength of the hydrogen bonds
      are nearly similar and do not show any marked dependence with the ring size of
      the hydrogen bond acceptor. The equilibrium constants for the complexation were
      determined, and atoms-in-molecules (AIM) and natural bond orbital (NBO) analyses
      were performed to further investigate the intermolecular interactions. Regardless
      of the ring size, hydrogen bonds in the complexes showed similar strength, in
      agreement with the observed OH-stretching red shifts.

PMID- 29367624
TI  - T cells specific for post-translational modifications escape intrathymic
      tolerance induction.
AB  - Establishing effective central tolerance requires the promiscuous expression of
      tissue-restricted antigens by medullary thymic epithelial cells. However, whether
      central tolerance also extends to post-translationally modified proteins is not
      clear. Here we show a mouse model of autoimmunity in which disease development is
      dependent on post-translational modification (PTM) of the tissue-restricted self
      antigen collagen type II. T cells specific for the non-modified antigen undergo
      efficient central tolerance. By contrast, PTM-reactive T cells escape thymic
      selection, though the PTM variant constitutes the dominant form in the periphery.
      This finding implies that the PTM protein is absent in the thymus, or present at
      concentrations insufficient to induce negative selection of developing thymocytes
      and explains the lower level of tolerance induction against the PTM antigen. As
      the majority of self-antigens are post-translationally modified, these data raise
      the possibility that T cells specific for other self-antigens naturally subjected
      to PTM may escape central tolerance induction by a similar mechanism.

PMID- 29367626
TI  - IL-36/LXR axis modulates cholesterol metabolism and immune defense to
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb) is a life-threatening pathogen in humans.
      Bacterial infection of macrophages usually triggers strong innate immune
      mechanisms, including IL-1 cytokine secretion. The newer member of the IL-1
      family, IL-36, was recently shown to be involved in cellular defense against Mtb.
      To unveil the underlying mechanism of IL-36 induced antibacterial activity, we
      analyzed its role in the regulation of cholesterol metabolism, together with the
      involvement of Liver X Receptor (LXR) in this process. We report that, in Mtb
      infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and
      efflux via LXR. Moreover, IL-36 induces the expression of cholesterol-converting
      enzymes and the accumulation of LXR ligands, such as oxysterols. Ultimately, both
      IL-36 and LXR signaling play a role in the regulation of antimicrobial peptides
      expression and in Mtb growth restriction. These data provide novel evidence for
      the importance of IL-36 and cholesterol metabolism mediated by LXR in cellular
      host defense against Mtb.

PMID- 29367627
TI  - Diversity of meso-scale architecture in human and non-human connectomes.
AB  - Brain function is reflected in connectome community structure. The dominant view
      is that communities are assortative and segregated from one another, supporting
      specialized information processing. However, this view precludes the possibility
      of non-assortative communities whose complex inter-community interactions could
      engender a richer functional repertoire. We use weighted stochastic blockmodels
      to uncover the meso-scale architecture of Drosophila, mouse, rat, macaque, and
      human connectomes. We find that most communities are assortative, though others
      form core-periphery and disassortative structures, which better recapitulate
      observed patterns of functional connectivity and gene co-expression in human and
      mouse connectomes compared to standard community detection techniques. We define
      measures for quantifying the diversity of communities in which brain regions
      participate, showing that this measure is peaked in control and subcortical
      systems in humans, and that inter-individual differences are correlated with
      cognitive performance. Our report paints a more diverse portrait of connectome
      communities and demonstrates their cognitive relevance.

PMID- 29367629
TI  - Lighting-from-above prior in biological motion perception.
AB  - The visual system is able to recognize body motion from impoverished stimuli.
      This requires combining stimulus information with visual priors. We present a new
      visual illusion showing that one of these priors is the assumption that bodies
      are typically illuminated from above. A change of illumination direction from
      above to below flips the perceived locomotion direction of a biological motion
      stimulus. Control experiments show that the underlying mechanism is different
      from shape-from-shading and directly combines information about body motion with
      a lighting-from-above prior. We further show that the illusion is critically
      dependent on the intrinsic luminance gradients of the most mobile parts of the
      moving body. We present a neural model with physiologically plausible mechanisms
      that accounts for the illusion and shows how the illumination prior might be
      encoded within the visual pathway. Our experiments demonstrate, for the first
      time, a direct influence of illumination priors in high-level motion vision.

PMID- 29367628
TI  - The inhibition of UBC13 expression and blockage of the DNMT1-CHFR-Aurora A
      pathway contribute to paclitaxel resistance in ovarian cancer.
AB  - Paclitaxel is widely used as a first-line chemotherapeutic drug for patients with
      ovarian cancer and other solid cancers, but drug resistance occurs frequently,
      resulting in ovarian cancer still presenting as the highest lethality among all
      gynecological tumors. Here, using DIGE quantitative proteomics, we identified
      UBC13 as down-regulated in paclitaxel-resistant ovarian cancer cells, and it was
      further revealed by immunohistochemical staining that UBC13 low-expression was
      associated with poorer prognosis and shorter survival of the patients. Through
      gene function experiments, we found that paclitaxel exposure induced UBC13 down
      regulation, and the enforced change in UBC13 expression altered the sensitivity
      to paclitaxel. Meanwhile, the reduction of UBC13 increased DNMT1 levels by
      attenuating its ubiquitination, and the up-regulated DNMT1 enhanced the CHFR
      promoter DNA methylation levels, leading to a reduction of CHFR expression, and
      an increased in the levels of Aurora A. Our findings revealed a novel function
      for UBC13 in regulating paclitaxel sensitivity through a DNMT1-CHFR-Aurora A
      pathway in ovarian cancer cells. UBC13 could potentially be employed as a
      therapeutic molecular drug for reversing paclitaxel resistance in ovarian cancer
      patients.

PMID- 29367630
TI  - Assessing fatty acid oxidation flux in rodent cardiomyocyte models.
AB  - The healthy adult heart primarily relies on fatty acid oxidation (FAO) for energy
      production but instantaneously adapts its substrate preference in response to
      physiological or pathological challenges. Accurate FAO measurements are crucial
      to investigate early metabolic (mal)adaptations. While measurements in intact
      cardiomyocytes offer greater physiological relevance, current FAO protocols
      mainly employ cell-free systems and/or require expensive equipment. Here, we
      present an easy-to-use, inexpensive, and sensitive method to measure, compare and
      modulate FAO in various cardiomyocyte models. Basal FAO was 2-fold higher in
      fresh versus cultured adult rat cardiomyocytes (aRCM), while OXPHOS protein
      levels were maintained. Basal FAO was higher in cultured (3-fold) and fresh (8
      fold) aRCM, versus widely used neonatal rat cardiomyocytes (nRCM) and mouse HL1
      cardiomyocytes. Moreover, we utilized chemical and pharmacological treatments in
      order to modulate the FAO flux at different cellular signalling levels. Our data
      indicate that caution should be taken when studying metabolism in nRCM and HL1
      cell models, as these display significantly lower FAO than aRCM. Accurate FAO
      measurement in cultured aRCM opens new avenues for studying the complex
      cardiomyocyte metabolic responses to mechanical, nutritional, pharmacological,
      and genetic manipulations.

PMID- 29367631
TI  - Author Correction: Analytic model for the complex effective index of the leaky
      modes of tube-type anti-resonant hollow core fibers.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29367632
TI  - Real-time colour hologram generation based on ray-sampling plane with multi-GPU
      acceleration.
AB  - Although electro-holography can reconstruct three-dimensional (3D) motion
      pictures, its computational cost is too heavy to allow for real-time
      reconstruction of 3D motion pictures. This study explores accelerating colour
      hologram generation using light-ray information on a ray-sampling (RS) plane with
      a graphics processing unit (GPU) to realise a real-time holographic display
      system. We refer to an image corresponding to light-ray information as an RS
      image. Colour holograms were generated from three RS images with resolutions of
      2,048 * 2,048; 3,072 * 3,072 and 4,096 * 4,096 pixels. The computational results
      indicate that the generation of the colour holograms using multiple GPUs (NVIDIA
      Geforce GTX 1080) was approximately 300-500 times faster than those generated
      using a central processing unit. In addition, the results demonstrate that 3D
      motion pictures were successfully reconstructed from RS images of 3,072 * 3,072
      pixels at approximately 15 frames per second using an electro-holographic
      reconstruction system in which colour holograms were generated from RS images in
      real time.

PMID- 29367633
TI  - Writing and reading antiferromagnetic Mn2Au by Neel spin-orbit torques and large
      anisotropic magnetoresistance.
AB  - Using antiferromagnets as active elements in spintronics requires the ability to
      manipulate and read-out the Neel vector orientation. Here we demonstrate for
      Mn2Au, a good conductor with a high ordering temperature suitable for
      applications, reproducible switching using current pulse generated bulk spin
      orbit torques and read-out by magnetoresistance measurements. Reversible and
      consistent changes of the longitudinal resistance and planar Hall voltage of star
      patterned epitaxial Mn2Au(001) thin films were generated by pulse current
      densities of ?107 A/cm2. The symmetry of the torques agrees with theoretical
      predictions and a large read-out magnetoresistance effect of more than ?6% is
      reproduced by ab initio transport calculations.

PMID- 29367634
TI  - Guanylate cyclase C reduces invasion of intestinal epithelial cells by bacterial
      pathogens.
AB  - The guanylate cyclase C (GC-C) receptor regulates electrolyte and water secretion
      into the gut following activation by the E. coli enterotoxin STa, or by weaker
      endogenous agonists guanylin and uroguanylin. Our previous work has demonstrated
      that GC-C plays an important role in controlling initial infection as well as
      carrying load of non-invasive bacterial pathogens in the gut. Here, we use
      Salmonella enterica serovar Typhimurium to determine whether GC-C signaling is
      important in host defense against pathogens that actively invade enterocytes. In
      vitro studies indicated that GC-C signaling significantly reduces Salmonella
      invasion into Caco2-BBE monolayers. Relative to controls, GC-C knockout mice
      develop severe systemic illness following oral Salmonella infection,
      characterized by disrupted intestinal mucus layer, elevated cytokines and organ
      CFUs, and reduced animal survival. In Salmonella-infected wildtype mice, oral
      gavage of GC-C agonist peptide reduced host/pathogen physical interaction and
      diminished bacterial translocation to mesenteric lymph nodes. These studies
      suggest that early life susceptibility to STa-secreting enterotoxigenic E. coli
      may be counter-balanced by a critical role of GC-C in protecting the mucosa from
      non-STa producing, invasive bacterial pathogens.

PMID- 29367636
TI  - Effect of spin relaxations on the spin mixing conductances for a bilayer
      structure.
AB  - The spin current can result in a spin-transfer torque in the normal-metal(NM)
      ferromagnetic-insulator(FMI) or normal-metal(NM)-ferromagnetic-metal(FMM)
      bilayer. In the earlier study on this issue, the spin relaxations were ignored or
      introduced phenomenologically. In this paper, considering the FMM or FMI with
      spin relaxations described by a non-Hermitian Hamiltonian, we derive an effective
      spin-transfer torque and an effective spin mixing conductance in the non
      Hermitian bilayer. The dependence of the effective spin mixing conductance on the
      system parameters (such as insulating gap, s-d coupling, and layer thickness) as
      well as the relations between the real part and the imaginary part of the
      effective spin mixing conductance are given and discussed. We find that the
      effective spin mixing conductance can be enhanced in the non-Hermitian system.
      This provides us with the possibility to enhance the spin mixing conductance.

PMID- 29367635
TI  - Antimicrobial activity of Ti-ZrN/Ag coatings for use in biomaterial applications.
AB  - Severely broken bones often require external bone fixation pins to provide
      support but they can become infected. In order to reduce such infections, novel
      solutions are required. Titanium zirconium nitride (Ti-ZrN) and Ti-ZrN silver (Ti
      ZrN/Ag) coatings were deposited onto stainless steel. Surface microtopography
      demonstrated that on the silver containing surfaces, S a and S v values
      demonstrated similar trends whilst the R a , average height and RMS value and S p
      values increased with increasing silver concentration. On the Ti-ZrN/Ag coatings,
      surface hydrophobicity followed the same trend as the S a and S v values. An
      increase in dead Staphylococcus aureus and Staphylococcus epidermidis cells was
      observed on the coatings with a higher silver concentration. Using CTC staining,
      a significant increase in S. aureus respiration on the silver containing surfaces
      was observed in comparison to the stainless steel control whilst against S.
      epidermidis, no significant difference in viable cells was observed across the
      surfaces. Cytotoxicity testing revealed that the TiZrN coatings, both with and
      without varying silver concentrations, did not possess a detrimental effect to a
      human monocyte cell line U937. This work demonstrated that such coatings have the
      potential to reduce the viability of bacteria that result in pin tract
      infections.

PMID- 29367637
TI  - Rosmarinic acid attenuates cardiac fibrosis following long-term pressure overload
      via AMPKalpha/Smad3 signaling.
AB  - Agonists of peroxisome proliferator-activated receptor gamma (PPAR-gamma) can
      activate 5' AMP-activated protein kinase alpha (AMPKalpha) and exert
      cardioprotective effects. A previous study has demonstrated that rosmarinic acid
      (RA) can activate PPAR-gamma, but its effect on cardiac remodeling remains
      largely unknown. Our study aimed to investigate the effect of RA on cardiac
      remodeling and to clarify the underlying mechanism. Mice were subjected to aortic
      banding to generate pressure overload induced cardiac remodeling and then were
      orally administered RA (100 mg/kg/day) for 7 weeks beginning 1 week after
      surgery. The morphological examination, echocardiography, and molecular markers
      were used to evaluate the effects of RA. To ascertain whether the beneficial
      effect of RA on cardiac fibrosis was mediated by AMPKalpha, AMPKalpha2 knockout
      mice were used. Neonatal rat cardiomyocytes and fibroblasts were separated and
      cultured to validate the protective effect of RA in vitro. RA-treated mice
      exhibited a similar hypertrophic response as mice without RA treatment, but had
      an attenuated fibrotic response and improved cardiac function after pressure
      overload. Activated AMPKalpha was essential for the anti-fibrotic effect of RA
      via inhibiting the phosphorylation and nuclear translocation of Smad3 in vivo and
      in vitro, and AMPKalpha deficiency abolished RA-mediated protective effects.
      Small interfering RNA against Ppar-gamma (siPpar-gamma) and GW9662, a specific
      antagonist of PPAR-gamma, abolished RA-mediated AMPKalpha phosphorylation and
      alleviation of fibrotic response in vitro. RA attenuated cardiac fibrosis
      following long-term pressure overload via AMPKalpha/Smad3 signaling and PPAR
      gamma was required for the activation of AMPKalpha. RA might be a promising
      therapeutic agent against cardiac fibrosis.

PMID- 29367638
TI  - A new dry eye mouse model produced by exorbital and intraorbital lacrimal gland
      excision.
AB  - Chronic dry eye is an increasingly prevalent condition worldwide, with resulting
      loss of visual function and quality of life. Relevant, repeatable, and stable
      animal models of dry eye are still needed. We have developed an improved surgical
      mouse model for dry eye based on severe aqueous fluid deficiency, by excising
      both the exorbital and intraorbital lacrimal glands (ELG and ILG, respectively)
      of mice. After ELG plus ILG excision, dry eye symptoms were evaluated using
      fluorescein infiltration observation, tear production measurement, and
      histological evaluation of ocular surface. Tear production in the model mice was
      significantly decreased compared with the controls. The corneal fluorescein
      infiltration score of the model mice was also significantly increased compared
      with the controls. Histological examination revealed significant severe
      inflammatory changes in the cornea, conjunctiva or meibomian glands of the model
      mice after surgery. In the observation of LysM-eGFP(+/-) mice tissues,
      postsurgical infiltration of green fluorescent neutrophils was observed in the
      ocular surface tissues. We theorize that the inflammatory changes on the ocular
      surface of this model were induced secondarily by persistent severe tear
      reduction. The mouse model will be useful for investigations of both
      pathophysiology as well as new therapies for tear-volume-reduction type dry eye.

PMID- 29367639
TI  - Conformational folding and disulfide bonding drive distinct stages of protein
      structure formation.
AB  - The causal relationship between conformational folding and disulfide bonding in
      protein oxidative folding remains incompletely defined. Here we show a stage
      dependent interplay between the two events in oxidative folding of C-reactive
      protein (CRP) in live cells. CRP is composed of five identical subunits, which
      first fold spontaneously to a near-native core with a correctly positioned C
      terminal helix. This process drives the formation of the intra-subunit disulfide
      bond between Cys36 and Cys97. The second stage of subunit folding, however, is a
      non-spontaneous process with extensive restructuring driven instead by the intra
      subunit disulfide bond and guided by calcium binding-mediated anchoring. With the
      folded subunits, pentamer assembly ensues. Our results argue that folding
      spontaneity is the major determinant that dictates which event acts as the
      driver. The stepwise folding pathway of CRP further suggests that one major route
      might be selected out of the many in theory for efficient folding in the cellular
      environment.

PMID- 29367640
TI  - Decoherence and control of a qubit in spin baths: an exact master equation study.
AB  - In spin-based nanosystems for quantum information processing, electron spin
      qubits are subject to decoherence due to their interactions with nuclear spin
      environments. In this paper, we present an exact master equation for a central
      spin-1/2 system in time-dependent external fields and coupled to a spin-half bath
      in terms of hyperfine interaction. The master equation provides a unified
      description for free and controlled dynamics of the central spin and is formally
      independent of the details and size of spin environments. Different from the
      previous approaches, the master equation remains exact even in the presence of
      external control fields. Using the parameters for realistic nanosystems with
      nonzero nuclear spins, such as GaAs, we investigate the Overhauser's effect on
      the decoherence dynamics of the central spin under different distributions of
      bath-spin frequencies and system-bath coupling strengths. Furthermore, we apply
      the leakage elimination operator, in a nonperturbative manner, to this system to
      suppress the decoherence induced by hyperfine interaction.

PMID- 29367642
TI  - The gait speed advantage of taller stature is lost with age.
AB  - Taller individuals walk faster but it is unknown whether this advantage persists
      at older ages. We examined the cross-sectional/longitudinal associations of
      height with gait speed (GS) in participants from the Dijon-Three-City cohort
      study (France) over 11 years. In 4011 participants (65-85 y), we measured
      usual/fast GS (6 m) up to five times. We examined whether the baseline height-GS
      association varied with age using linear regression, and whether height
      influenced GS change using linear mixed models. Taller participants 65 y at
      baseline walked faster than shorter ones (fast GS difference between top/bottom
      height quartiles, 0.100 m/s, P < 0.001); this association weakened with age (P
      interaction = 0.02), with a 0.012 m/s (P = 0.57) difference at 80 y. Ten-year
      fast GS decline was 51% greater (P < 0.001) in younger participants in the top
      height quartile (-0.183 m/s) compared to those in the bottom quartile (-0.121
      m/s), leading the GS difference between the two groups to be attenuated by 50%
      over the follow-up. The height-related difference in fast GS decline was not
      explained by time-dependent comorbidities or height shrinkage. Analyses for usual
      GS yielded consistent findings. The height-GS relation is more complex than
      previously thought, as the height related advantage in GS disappears as persons
      grow older due to faster decline in taller compared to shorter persons.

PMID- 29367644
TI  - Intravitreal injection of aflibercept, an anti-VEGF antagonist, down-regulates
      plasma von Willebrand factor in patients with age-related macular degeneration.
AB  - We investigated the association between von Willebrand factor (VWF) and exudative
      age-related macular degeneration (AMD) in 114 Japanese patients. Intravitreal
      injection of vascular endothelial growth factor (VEGF) inhibitor is the most
      effective therapy for AMD. Therefore, we analyzed changes of VWF antigen (VWF:Ag)
      and VWF multimers (VWFMs) after intravitreal injection of aflibercept, an anti
      VEGF antagonist. The relationship between polymorphisms in complement factor H
      (p.Y402H and p.I62V) and AMD was previously reported. In our patients, p.I62V,
      but not p.Y402H, was significantly associated with an increased risk of AMD. Pre
      treatment plasma levels of VWF:Ag in patients with AMD were significantly higher
      than those in controls. Unusually large VWFMs (UL-VWFMs) were detected in the
      majority of AMD patients with concurrent vitreous or subretinal hemorrhage. After
      intravitreal injection of aflibercept, plasma levels of VWF:Ag and VEGF-A were
      significantly decreased. UL-VWFMs disappeared after aflibercept injection in
      three cases, but persisted even 1 month after injection in the other five cases.
      In conclusion, plasma VWF:Ag levels were significantly elevated in patients with
      AMD, and decreased after intravitreal aflibercept injection. VWF may play an
      important role in the pathophysiology of AMD, and aflibercept might improve AMD
      by reducing plasma levels of VWF in addition to VEGF-A.

PMID- 29367643
TI  - Characterization of Dopaminergic System in the Striatum of Young Adult Park2-/-
      Knockout Rats.
AB  - Mutations in parkin gene (Park2) are linked to early-onset autosomal recessive
      Parkinson's disease (PD) and young-onset sporadic PD. Park2 knockout (PKO)
      rodents; however, do not display neurodegeneration of the nigrostriatal pathway,
      suggesting age-dependent compensatory changes. Our goal was to examine
      dopaminergic (DAergic) system in the striatum of 2 month-old PKO rats in order to
      characterize compensatory mechanisms that may have occurred within the system.
      The striata form wild type (WT) and PKO Long Evans male rats were assessed for
      the levels of DAergic markers, for monoamine oxidase (MAO) A and B activities and
      levels, and for the levels of their respective preferred substrates, serotonin (5
      HT) and beta-phenylethylamine (beta-PEA). The PKO rats displayed lower activities
      of MAOs and higher levels of beta-PEA in the striatum than their WT counterparts.
      Decreased levels of beta-PEA receptor, trace amine-associated receptor 1 (TAAR
      1), and postsynaptic DA D2 (D2L) receptor accompanied these alterations. Drug
      naive PKO rats displayed normal locomotor activity; however, they displayed
      decreased locomotor response to a low dose of psychostimulant methamphetamine,
      suggesting altered DAergic neurotransmission in the striatum when challenged with
      an indirect agonist. Altogether, our findings suggest that 2 month-old PKO male
      rats have altered DAergic and trace aminergic signaling.

PMID- 29367645
TI  - CD40L mediated alternative NFkappaB-signaling induces resistance to BCR
      inhibitors in patients with mantle cell lymphoma.
AB  - Drug resistance is a significant obstacle in cancer treatment and therefore a
      frequent subject of research. Developed or primary resistance limits the
      treatment success of inhibitors of the B cell receptor (BCR) pathway in mantle
      cell lymphoma (MCL) patients. Recent research has highlighted the role of the
      nuclear factor-kappa B (NFkappaB) pathway in the context of resistance to BCR
      inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on
      NFkappaB signaling and illustrated the ability of CD40L to activate the
      alternative NFkappaB pathway in MCL. This activation leads to independency of
      classical NFkappaB signaling and results in resistance to BCR inhibitors.
      Therefore, ligands (such as CD40L) and their activation of the alternative
      NFkappaB pathway have a major impact on the drug response in MCL. Furthermore,
      this study indicates a protective role for cells expressing specific ligands as
      microenvironmental niches for MCL cells and underlines the significance of
      therapeutically targeting alternative NFkappaB signaling in MCL.

PMID- 29367641
TI  - C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable
      AMPA receptor-mediated excitotoxicity.
AB  - Mutations in C9ORF72 are the most common cause of familial amyotrophic lateral
      sclerosis (ALS). Here, through a combination of RNA-Seq and electrophysiological
      studies on induced pluripotent stem cell (iPSC)-derived motor neurons (MNs), we
      show that increased expression of GluA1 AMPA receptor (AMPAR) subunit occurs in
      MNs with C9ORF72 mutations that leads to increased Ca2+-permeable AMPAR
      expression and results in enhanced selective MN vulnerability to excitotoxicity.
      These deficits are not found in iPSC-derived cortical neurons and are abolished
      by CRISPR/Cas9-mediated correction of the C9ORF72 repeat expansion in MNs. We
      also demonstrate that MN-specific dysregulation of AMPAR expression is also
      present in C9ORF72 patient post-mortem material. We therefore present multiple
      lines of evidence for the specific upregulation of GluA1 subunits in human mutant
      C9ORF72 MNs that could lead to a potential pathogenic excitotoxic mechanism in
      ALS.

PMID- 29367646
TI  - Vascular endothelial effects of collaborative binding to platelet/endothelial
      cell adhesion molecule-1 (PECAM-1).
AB  - Targeting drugs to endothelial cells has shown the ability to improve outcomes in
      animal models of inflammatory, ischemic and thrombotic diseases. Previous studies
      have revealed that certain pairs of ligands (antibodies and antibody fragments)
      specific for adjacent, but distinct, epitopes on PECAM-1 enhance each other's
      binding, a phenomenon dubbed Collaborative Enhancement of Paired Affinity
      Ligands, or CEPAL. This discovery has been leveraged to enable simultaneous
      delivery of multiple therapeutics to the vascular endothelium. Given the known
      role of PECAM-1 in promoting endothelial quiescence and cell junction integrity,
      we sought here to determine if CEPAL might induce unintended vascular effects.
      Using a combination of in vitro and in vivo techniques and employing human and
      mouse endothelial cells under physiologic and pathologic conditions, we found
      only modest or non-significant effects in response to antibodies to PECAM-1,
      whether given solo or in pairs. In contrast, these methods detected significant
      elevation of endothelial permeability, pro-inflammatory vascular activation, and
      systemic cytokine release following antibody binding to the related endothelial
      junction protein, VE-Cadherin. These studies support the notion that PECAM-1
      targeted CEPAL provides relatively well-tolerated endothelial drug delivery.
      Additionally, the analysis herein creates a template to evaluate potential
      toxicities of vascular-targeted nanoparticles and protein therapeutics.

PMID- 29367648
TI  - Prognostic impact of a past or synchronous second cancer in diffuse large B cell
      lymphoma.

PMID- 29367647
TI  - Proteomic Analysis of Nucleus Pulposus Cell-derived Extracellular Matrix Niche
      and Its Effect on Phenotypic Alteration of Dermal Fibroblasts.
AB  - Reconstituting biomimetic matrix niche in vitro and culturing cells at the cell
      niche interface is necessary to understand the effect and function of the
      specific matrix niche. Here we attempted to reconstitute a biomimetic
      extracellular matrix (ECM) niche by culturing nucleus pulposus cells (NPCs) in a
      collagen microsphere system previously established and allowing them to remodel
      the template matrix. The reconstituted NPC-derived complex ECM was obtained after
      decellularization and the composition of such niche was evaluated by proteomic
      analysis. Results showed that a complex acellular matrix niche consisting of ECM
      proteins and cytoskeletal proteins by comparing with the template collagen matrix
      starting material. In order to study the significance of the NPC-derived matrix
      niche, dermal fibroblasts were repopulated in such niche and the phenotypes of
      these cells were changed, gene expression of collagen type II and CA12 increased
      significantly. A biomimetic NPC-derived cell niche consisting of complex ECM can
      be reconstituted in vitro, and repopulating such matrix niche with fibroblasts
      resulted in changes in phenotypic markers. This work reports a 3D in vitro model
      to study cell niche factors, contributing to future understanding of cellular
      interactions at the cell-niche interface and rationalized scaffold design for
      tissue engineering.

PMID- 29367649
TI  - Del11q-positive CLL lymphocytes exhibit altered glutamine metabolism and
      differential response to GLS1 and glucose metabolism inhibition.

PMID- 29367650
TI  - HOXC8 promotes proliferation and migration through transcriptional up-regulation
      of TGFbeta1 in non-small cell lung cancer.
AB  - Homeobox (HOX) genes encode a family of transcription factors, which play crucial
      roles in numerous processes, and their dysregulation is involved in the
      carcinogenesis of many human cancers. In the present study, we investigated the
      roles of HOXC8 in non-small cell lung cancer (NSCLC). We showed that HOXC8 was
      upregulated in clinical NSCLC specimens compared to normal lung tissues, and the
      high expression of HOXC8 correlated with tumor node metastasis (TNM) stage, tumor
      status, lymph nodal status and poor relapse-free survival for lung cancer
      patients. Functionally, HOXC8 expression significantly promoted the
      proliferation, anchorage-independent growth and migration of NSCLC, and HOXC8
      functioned as a transcription activator to induce the expression of TGFbeta1,
      leading to an increase in the proliferation, anchorage-independent growth and
      migration of NSCLC. Furthermore, we demonstrated that HOXC8 expression was
      associated with chemoresistance and anti-apoptosis in NSCLC, suggesting that
      HOXC8 is a promising therapeutic target for chemosensitization of NSCLC to
      cisplatin. Altogether, our study defined a critical role of HOXC8 in promoting
      transcription of TGFbeta1 and NSCLC tumorigenesis.

PMID- 29367651
TI  - Embryonic Surface Ectoderm-specific Mitofusin 2 Conditional Knockout Induces
      Congenital Cataracts in Mice.
AB  - Inherited mitochondrial mutations can result in mitochondrial dysfunction or
      stochastic oxidative damage. Cumulative mitochondrial damage is an important
      factor in age-related disorders, such as cataracts and macular degeneration. Mfn2
      mediates the fusion of mitochondria and contribute to the dynamic balance between
      fusion and fission that determines mitochondria morphology. We report here that
      conditional loss of Mfn2 function in the head surface ectoderm leads to a range
      of congenital eye defects, including small, opacified lens and small eyeball in
      the most severe phenotypes. The Le-Cre transgenic mouse line and Mfn2 flox mouse
      line were used in this study to generate Mfn2 conditional knockout mice. Our
      study revealed Mfn2 gene function in lens development and addressed the
      relationship between the mitochondria and lens transparency. Conditional loss of
      Mfn2 affected lens epithelium cell proliferation, apoptosis and ultrastructure of
      mitochondria. We conclude that proper development of the lens and lens
      transparency depend on normal Mfn2 gene function.

PMID- 29367652
TI  - 9c11tCLA modulates 11t18:1 and 9t18:1 induced inflammations differently in human
      umbilical vein endothelial cells.
AB  - Endothelial inflammation is recognized as the initial stage of a multistep
      process leading to coronary heart disease (CHD). Recently, the different effects
      of industrial trans fatty acids (elaidic acid, 9t18:1) and ruminant trans fatty
      acids (vaccenic acid, 11t18:1) on CHD have been reported in epidemiological and
      animal studies, however, the mechanism was not fully studied. Therefore, the
      objective of this study was to explore the underlying mechanism by which 9t18:1
      and 11t18:1 affect human umbilical vein endothelial cells (HUVECs) inflammation.
      We found that 9c11t-CLA modulated the inflammation of HUVECs induced by 9t18:1
      and 11t18:1. Fatty acid composition, pro-inflammatory factors, phosphorylation of
      MAPKs, and the TLR4 level in HUVECs altered by 11t18:1 induction, collectively
      suggest that the bio-conversion of 11t18:1 to 9c11tCLA might be the cause why
      11t18:1 and 9t18:1 have distinct influences on endothelial injuries. It was
      concluded that it is biosynthesis of 9c11t CLA from11t18:1, and the modulation of
      TLR4-MAPK pathway by 9c11t CLA, which at least partially account for the slight
      effect of 11t18:1 on endothelial inflammation.

PMID- 29367653
TI  - Investigation of radiomic signatures for local recurrence using primary tumor
      texture analysis in oropharyngeal head and neck cancer patients.
AB  - Radiomics is one such "big data" approach that applies advanced image
      refining/data characterization algorithms to generate imaging features that can
      quantitatively classify tumor phenotypes in a non-invasive manner. We hypothesize
      that certain textural features of oropharyngeal cancer (OPC) primary tumors will
      have statistically significant correlations to patient outcomes such as local
      control. Patients from an IRB-approved database dispositioned to
      (chemo)radiotherapy for locally advanced OPC were included in this retrospective
      series. Pretreatment contrast CT scans were extracted and radiomics-based
      analysis of gross tumor volume of the primary disease (GTVp) were performed using
      imaging biomarker explorer (IBEX) software that runs in Matlab platform. Data set
      was randomly divided into a training dataset and test and tuning holdback
      dataset. Machine learning methods were applied to yield a radiomic signature
      consisting of features with minimal overlap and maximum prognostic significance.
      The radiomic signature was adapted to discriminate patients, in concordance with
      other key clinical prognosticators. 465 patients were available for analysis. A
      signature composed of 2 radiomic features from pre-therapy imaging was derived,
      based on the Intensity Direct and Neighbor Intensity Difference methods. Analysis
      of resultant groupings showed robust discrimination of recurrence probability and
      Kaplan-Meier-estimated local control rate (LCR) differences between "favorable"
      and "unfavorable" clusters were noted.

PMID- 29367655
TI  - Author Correction: Is body-weight supported treadmill training or robotic
      assisted gait training superior to overground gait training and other forms of
      physiotherapy in people with spinal cord injury? A systematic review.
AB  - The original article can be found online at https://doi.org/10.1038/sc.2017.31 .

PMID- 29367654
TI  - Prevalence of upper extremity pain in a population of people with paraplegia.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To determine the prevalence,
      patterns, and predictors of musculoskeletal pain in the upper extremity joints
      among wheelchair-dependent individuals with post-traumatic paraplegia.
      Secondarily, to document most common reported causes of upper extremity pain.
      SETTING: Centre for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Germany.
      METHODS: The study was done by means of a structured questionnaire, which was
      mailed to the individuals who had been treated between 1990 and 2007 for newly
      sustained or pre-existing, accident-related paraplegia (n = 670). The
      questionnaire was designed mainly to obtain the information regarding shoulder,
      elbow, and wrist pain. Additional data included participant demographics,
      mechanism, level and completeness of injury as well as wheelchair dependence and
      time since injury. The Frankel classification system was used to define the
      completeness of injury. RESULTS: Four hundred and fifty-one (67%) questionnaires
      were included. Pain was reported by approximately 81% of the participants. Of
      this sample, 61% had shoulder pain, 33% had elbow pain, and 43% had wrist pain,
      19% had shoulder, elbow, and wrist pain, 27% had shoulder and elbow pain, 34% had
      shoulder and wrist pain, 21% had elbow and wrist pain. The main diagnoses were
      rotator cuff tears for individuals with shoulder pain, epicondylitis for those
      with elbow pain, and carpal tunnel syndrome for those with wrist pain. The
      development of shoulder/elbow and wrist pain correlated with age and time since
      injury. CONCLUSIONS: Age and the length of time since injury correlated with a
      higher rate of shoulder, elbow, and wrist pain. The completeness of injury,
      neurological level, and gender were correlated with shoulder, elbow, and wrist
      pain, respectively.

PMID- 29367656
TI  - Patient participation from the perspective of staff members working in spinal
      cord injury rehabilitation.
AB  - STUDY DESIGN: Qualitative method, semi-structured interviews. OBJECTIVES: The
      aims of this study were to explore the meaning of patient participation from the
      perspective of staff members working with spinal cord injury (SCI)
      rehabilitation, and what they saw as requisites for and constraints to patient
      participation. SETTING: Swedish spinal injury unit. METHODS: Interviews with 13
      staff members at a spinal unit were conducted individually and analyzed by means
      of content analysis. RESULTS: One category describing patient participation
      emerged from the interviews: Patient - a team member. Four categories were
      extracted as requisites: Communication; information and knowledge; routines;
      respecting the patient as a unique person; and an open climate. Three categories
      of constraints were identified: Understaffing and new staff members; patients'
      inability to grasp information; and structures and fragmented responsibilities.
      CONCLUSIONS: The informants were unanimous in stating that the patient is an
      integral and natural member of the rehabilitation team. Recognizing the person
      with SCI as a team member acknowledges and endorses the patient as a person with
      capabilities to participate in his or her rehabilitation. The patient as a person
      also means that he or she has unique needs and preferences, which the staff
      members must accommodate. This is also fundamental in a person-centered approach.
      Therefore, the viewpoints of the informants may be useful for other settings to
      enhance person centeredness and patient participation.

PMID- 29367658
TI  - Variations among Streptococcus gallolyticus subsp. gallolyticus strains in
      connection with colorectal cancer.
AB  - Streptococcus gallolyticus subsp. gallolyticus (Sg) has long been reported to
      display a strong association with colorectal cancer (CRC). It was recently
      demonstrated to actively promote the development of CRC, underscoring the
      importance of Sg in both clinical correlation and functional relevance in CRC.
      Here we investigated several clinical isolates of Sg in their interactions with
      human colon cancer cells and in mouse models. Some Sg strains were able to
      stimulate host cell proliferation (proliferation-promoting Sg, PP-Sg) whereas
      others were not (non-proliferation-promoting Sg, NP-Sg). PP-Sg strains adhered to
      colon cancer cells much better than NP-Sg strains, suggesting that close contact
      between Sg and host cells is important. In mice, PP-Sg is significantly better at
      colonizing the colon tissues of A/J mice compared to NP-Sg, however this
      difference was not observed in C57BL/6 mice, suggesting that Sg colonization of
      mouse colon tissues involves specific interactions between bacterial and host
      factors on the colonic epithelium. Finally, in an azoxymethane-induced mouse
      model of CRC, PP-Sg promoted tumor development whereas NP-Sg did not. These
      findings provide clues to the mechanism underlying the Sg-CRC association and
      have important implications to clinical studies that aim to correlate Sg with
      clinical and pathological features of CRC.

PMID- 29367657
TI  - Phylogenomics and antimicrobial resistance of the leprosy bacillus Mycobacterium
      leprae.
AB  - Leprosy is a chronic human disease caused by the yet-uncultured pathogen
      Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over
      200,000 new cases are still reported annually. Here, we obtain M. leprae genome
      sequences from DNA extracted directly from patients' skin biopsies using a
      customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25
      countries provides insight into evolution and antimicrobial resistance,
      uncovering lineages and phylogeographic trends, with the most ancestral strains
      linked to the Far East. In addition to known MDT-resistance mutations, we detect
      other mutations associated with antibiotic resistance, and retrace a potential
      stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the
      previously undescribed mutations occur in genes that are apparently subject to
      positive selection, and two of these (ribD, fadD9) are restricted to drug
      resistant strains. Finally, nonsense mutations in the nth excision repair gene
      are associated with greater sequence diversity and drug resistance.

PMID- 29367659
TI  - Electric fields control the orientation of peptides irreversibly immobilized on
      radical-functionalized surfaces.
AB  - Surface functionalization of an implantable device with bioactive molecules can
      overcome adverse biological responses by promoting specific local tissue
      integration. Bioactive peptides have advantages over larger protein molecules due
      to their robustness and sterilizability. Their relatively small size presents
      opportunities to control the peptide orientation on approach to a surface to
      achieve favourable presentation of bioactive motifs. Here we demonstrate control
      of the orientation of surface-bound peptides by tuning electric fields at the
      surface during immobilization. Guided by computational simulations, a peptide
      with a linear conformation in solution is designed. Electric fields are used to
      control the peptide approach towards a radical-functionalized surface.
      Spontaneous, irreversible immobilization is achieved when the peptide makes
      contact with the surface. Our findings show that control of both peptide
      orientation and surface concentration is achieved simply by varying the solution
      pH or by applying an electric field as delivered by a small battery.

PMID- 29367660
TI  - Earthquake impacts on microcrustacean communities inhabiting groundwater-fed
      springs alter species-abundance distribution patterns.
AB  - Earthquakes are important natural events, yet their impacts on animal communities
      are poorly known. Understanding earthquake impacts on groundwater communities is
      essential to assess their resilience and hence to perform conservation actions.
      We investigated how a 6.3 Mw earthquake that occurred in 2009 altered the
      community structure (diversity, evenness, dominance, species abundance
      distributions and beta-diversity) of microcrustaceans (Crustacea Copepoda)
      inhabiting springs fed by the Gran Sasso Aquifer (Central Italy). Sampling was
      done in low-discharge (1997), high-discharge (2005), and post-seismic (2012)
      hydrological years. Stygobites (obligate groundwater species) and non-stygobites
      (non-obligate groundwater species) showed different patterns. A high-water
      discharge in 2005 altered abundance patterns of non-stygobites. The earthquake re
      established former abundance patterns. Stygobites were less affected by high
      water discharge in 2005, and showed strong increases in diversity and evenness
      after the earthquake. This effect was due to the fact that the earthquake induced
      a strong population decline of previously dominant stygobites (especially of
      Nitocrella pescei) in the aquifer, and subsequently at the main spring outlets,
      thus allowing a more equitable species-abundance distribution. These results
      highlight the importance of considering species ecology to understand the effects
      of a significant earthquake event on animal communities.

PMID- 29367661
TI  - Ultrasensitive reversible chromophore reaction of BODIPY functions as high ratio
      double turn on probe.
AB  - Chromophore reactions with changes to conjugation degree, especially those
      between the conjugated and unconjugated state, will bring a large spectral
      variation. To realize such a process, a meso-naked BODIPY (MNBOD) with two
      electron-withdrawing groups around the core is designed and synthesized. The
      resulting system is extremely sensitive to bases. The red, highly fluorescent
      solution readily becomes colorless and non-fluorescent after base addition;
      however, the color and fluorescence can be totally and instantly restored by
      addition of acid or formaldehyde. Analyses show that two identical MNBODs are
      connected by a C-C single bond (sp3) at the meso-position through a radical
      reaction that results in an unconjugated, colorless dimer complexed with bases.
      When the bases are consumed, the dimer immediately dissociates into the red,
      highly fluorescent, conjugated MNBOD monomer. With 260 nm spectral change and
      over 120,000 turn-on ratio, this chromophore-reaction can be utilized as a
      sensitive reaction-based dual-signal probe.

PMID- 29367663
TI  - Force depression following a stretch-shortening cycle is independent of stretch
      peak force and work performed during shortening.
AB  - The steady-state isometric force following active muscle shortening or
      lengthening is smaller (force depression; FD) or greater (residual force
      enhancement; RFE) than a purely isometric contraction at the corresponding
      length. The mechanisms behind these phenomena remain not fully understood, with
      few studies investigating the effects of FD and RFE in stretch-shortening cycles
      (SSC). The purpose of this study was to investigate the influence of RFE and peak
      force at the end of the stretch phase on the steady-state isometric force
      following shortening. Isometric thumb adduction force measurements were preceded
      by an isometric, a shortening contraction to induce FD, and SSCs at different
      stretch speeds (15 degrees /s, 60 degrees /s, and 120 degrees /s). The different
      peak force values at the end of stretch and the different amounts of work
      performed during shortening did not influence the steady-state isometric force at
      the end of the SSC. We conclude that the FD following SSC depends exclusively on
      the amount of RFE established in the initial stretch phase in situations where
      the timing and contractile conditions of the shortening phase are kept constant .

PMID- 29367662
TI  - Comprehensive profiling of the ligand binding landscapes of duplexed aptamer
      families reveals widespread induced fit.
AB  - Duplexed aptamers (DAs) are ligand-responsive constructs engineered by
      hybridizing an aptamer with an aptamer-complementary element (ACE, e.g., a DNA
      oligonucleotide). Although DAs are commonly deployed, the binding dynamics of
      ternary ACE-aptamer-ligand systems remain underexplored, having been
      conventionally described by a conformational selection framework. Here we
      introduce aptamer-complementary element scanning (ACE-Scan) as a method to
      generate comprehensive hybridization, spontaneous off-rate, and induced fit
      ligand-binding landscapes for entire DA families. ACE-Scan reveals induced fit in
      DAs engineered from small molecule- and protein-binding DNA and RNA aptamers, as
      well as DAs engineered from the natural add riboswitch aptamer. To validate ACE
      Scan, we engineer solution-phase ATP-specific DAs from 5 ACEs with varying
      spontaneous and induced fit off-rates, generating aptasensors with 8-fold
      differences in dynamic range consistent with ACE-Scan. This work demonstrates
      that ACE-Scan can readily map induced fit in DAs, empowering aptamers in
      biosensing, synthetic biology, and DNA nanomachines.

PMID- 29367664
TI  - Prolactin inhibits the progression of intervertebral disc degeneration through
      inactivation of the NF-kappaB pathway in rats.
AB  - Intervertebral disc degeneration (IVDD) is one of the key predisposing factors
      for low back pain. Although the exact mechanism remains unclear, inflammatory
      response and nucleus pulposus (NP) apoptosis are known to play important roles in
      this process. Prolactin protects against inflammation-associated chondrocyte
      apoptosis in arthritis. Based on prior studies, we hypothesized that prolactin
      might have therapeutic effects on IVDD by inhibiting the apoptosis of
      degenerative human disc NP cells. An experimental model of IVDD was established
      in 3-month-old Sprague-Dawley rats by submitting them to percutaneous disc
      puncture with a 20-gauge needle on levels 7-8 and 8-9 of the coccygeal vertebrae.
      Then the rats were injected with 20 or 200 ng prolactin on a weekly basis.
      Radiologic and histologic analyses were performed on days 4, 7, 14, and 28. The
      expression of prolactin and its receptor was analyzed in human tissue obtained
      from symptomatic patients undergoing microencoscopy discectomy, or from scoliosis
      patients undergoing deformity correction surgery. The results showed that
      intradiscal injection of prolactin maintained disc height and the mean signal
      intensity of the punctured disc. Histological analysis indicated that prolactin
      treatment significantly retained the complete structure of the NP and annulus
      fibrosus compared with the vehicle group. In addition, more collagen II, but
      fewer collagen I-containing tissues were detected in the prolactin treatment
      groups compared to the vehicle group. Moreover, low levels of tumor necrosis
      factor-alpha, interleukin-1beta, cleaved-caspase 3, and TUNEL staining were
      observed in the prolactin treatment groups. We also demonstrated that prolactin
      impaired puncture-induced inflammation and cell apoptosis by downregulating
      activation of the NF-kappaB pathway. The degenerated NP tissues from patients had
      decreased expression of prolactin and its receptor, whereas expression was
      increased in the NP tissues removed from scoliosis patients. These results
      suggest that prolactin may be a novel therapeutic target for the treatment of
      IVDD.

PMID- 29367665
TI  - The spatial and metabolic basis of colony size variation.
AB  - Spatial structure impacts microbial growth and interactions, with ecological and
      evolutionary consequences. It is therefore important to quantitatively understand
      how spatial proximity affects interactions in different environments. We tested
      how proximity influences colony size when either Escherichia coli or Salmonella
      enterica are grown on various carbon sources. The importance of colony location
      changed with species and carbon source. Spatially explicit, genome-scale
      metabolic modeling recapitulated observed colony size variation. Competitors that
      determine territory size, according to Voronoi diagrams, were the most important
      drivers of variation in colony size. However, the relative importance of
      different competitors changed through time. Further, the effect of location
      increased when colonies took up resources quickly relative to the diffusion of
      limiting resources. These analyses made it apparent that the importance of
      location was smaller than expected for experiments with S. enterica growing on
      glucose. The accumulation of toxic byproducts appeared to limit the growth of
      large colonies and reduced variation in colony size. Our work provides an
      experimentally and theoretically grounded understanding of how location interacts
      with metabolism and diffusion to influence microbial interactions.

PMID- 29367666
TI  - Surface waves magnitude estimation from ionospheric signature of Rayleigh waves
      measured by Doppler sounder and OTH radar.
AB  - Surface waves emitted after large earthquakes are known to induce atmospheric
      infrasonic waves detectable at ionospheric heights using a variety of techniques,
      such as high frequency (HF) Doppler, global positioning system (GPS), and
      recently over-the-horizon (OTH) radar. The HF Doppler and OTH radar are
      particularly sensitive to the ionospheric signature of Rayleigh waves and are
      used here to show ionospheric perturbations consistent with the propagation of
      Rayleigh waves related to 28 and 10 events, with a magnitude larger than 6.2,
      detected by HF Doppler and OTH radar respectively. A transfer function is
      introduced to convert the ionospheric measurement into the correspondent ground
      displacement in order to compare it with classic seismometers. The ground
      vertical displacement, measured at the ground by seismometers, and measured at
      the ionospheric altitude by HF Doppler and OTH radar, is used here to compute
      surface wave magnitude. The ionospheric surface wave magnitude (M siono )
      proposed here introduces a new way to characterize earthquakes observing the
      signature of surface Rayleigh waves in the ionosphere. This work proves that
      ionospheric observations are useful seismological data to better cover the Earth
      and to explore the seismology of the Solar system bodies observing the ionosphere
      of other planets.

PMID- 29367667
TI  - Quantitative Structure-Activity Relationship Model for HCVNS5B inhibitors based
      on an Antlion Optimizer-Adaptive Neuro-Fuzzy Inference System.
AB  - The global prevalence of hepatitis C Virus (HCV) is approximately 3% and one
      fifth of all HCV carriers live in the Middle East, where Egypt has the highest
      global incidence of HCV infection. Quantitative structure-activity relationship
      (QSAR) models were used in many applications for predicting the potential effects
      of chemicals on human health and environment. The adaptive neuro-fuzzy inference
      system (ANFIS) is one of the most popular regression methods for building a
      nonlinear QSAR model. However, the quality of ANFIS is influenced by the size of
      the descriptors, so descriptor selection methods have been proposed, although
      these methods are affected by slow convergence and high time complexity. To avoid
      these limitations, the antlion optimizer was used to select relevant descriptors,
      before constructing a nonlinear QSAR model based on the PIC50 and these
      descriptors using ANFIS. In our experiments, 1029 compounds were used, which
      comprised 579 HCVNS5B inhibitors (PIC50 < ~14) and 450 non-HCVNS5B inhibitors
      (PIC50 > ~14). The experimental results showed that the proposed QSAR model
      obtained acceptable accuracy according to different measures, where [Formula: see
      text] was 0.952 and 0.923 for the training and testing sets, respectively, using
      cross-validation, while [Formula: see text] was 0.8822 using leave-one-out (LOO).

PMID- 29367668
TI  - Honokiol is a FOXM1 antagonist.
AB  - Honokiol is a natural product and an emerging drug for a wide variety of
      malignancies, including hematopoietic malignancies, sarcomas, and common
      epithelial tumors. The broad range of activity of honokiol against numerous
      malignancies with diverse genetic backgrounds suggests that honokiol is
      inhibiting an activity that is common to multiple malignancies. Oncogenic
      transcription factor FOXM1 is one of the most overexpressed oncoproteins in human
      cancer. Here we found that honokiol inhibits FOXM1-mediated transcription and
      FOXM1 protein expression. More importantly, we found that honokiol's inhibitory
      effect on FOXM1 is a result of binding of honokiol to FOXM1. This binding is
      specific to honokiol, a dimerized allylphenol, and was not observed in compounds
      that either were monomeric allylphenols or un-substituted dihydroxy phenols. This
      indicates that both substitution and dimerization of allylphenols are required
      for physical interaction with FOXM1. We thus demonstrate a novel and specific
      mechanism for FOXM1 inhibition by honokiol, which partially may explain its
      anticancer activity in cancer cells.

PMID- 29367670
TI  - Publisher Correction: Stateful characterization of resistive switching TiO2 with
      electron beam induced currents.
AB  - The original version of this Article contained an error in Eq. 1. The arrows
      between the symbols "T" and "B", and "B" and "T", were written "<->" but should
      have been "->", and incorrectly read: IEBIC=IEBAC+ISEE+I(e<->h)+IEBICT<
      >B+IESEEB<->T The correct from of the Eq. 1 is as follows:IEBIC=IEBAC+ISEE+I(e<
      >h)+IEBICT->B+IESEEB->T This has now been corrected in both the PDF and HTML
      versions of the article.

PMID- 29367669
TI  - Investigation of 20S-hydroxyvitamin D3 analogs and their 1alpha-OH derivatives as
      potent vitamin D receptor agonists with anti-inflammatory activities.
AB  - 20S-hydroxyvitamin D3 [20S(OH)D3] is anti-inflammatory and not hypercalcemic,
      suggesting its potential as a lead compound. In this study, side chain modified
      20S(OH)D3 analogs (4, 13, 23 and 33) together with their 1alpha-OH derivatives
      were synthesized and their metabolism and biological activities tested. 4, 13 and
      23 are good substrates for CYP27B1, enabling enzymatic synthesis of their 1alpha
      OH derivatives 5, 14 and 24. However, 33 could not be hydroxylated by CYP27B1 and
      acts as an inhibitor. All analogs were poorer substrates for CYP24A1 than
      calcitriol, indicating improved catabolic stability. While the parent analogs
      showed minimal VDR stimulating activity, their 1alpha-OH derivatives were potent
      VDR agonists. 4, 5, 14 and 24 significantly upregulated the expression of CYP24A1
      at the mRNA level, consistent with their VDR activation abilities and indicating
      that 1alpha-hydroxylation is required to produce analogs with strong activity.
      These analogs have anti-inflammatory activities that are influenced by side chain
      composition and by 1alpha-hydroxylation. To understand their molecular
      interactions with the VDR, 20S(OH)D3, 4 and 33 were co-crystalized with the VDR
      ligand binding domain, which revealed subtle differences to the calcitriol-bound
      receptor. This study demonstrates the potential of the 20S(OH)D3 scaffold for the
      development of novel anti-inflammatory agents.

PMID- 29367671
TI  - Warming deferentially altered multidimensional soil legacy induced by past land
      use history.
AB  - The legacy effects of previous land use and climate history may affect current
      soil function. However, the manner in which these legacy effects of land use are
      modulated by the subsequent climate remains unclear. For this reason, we
      investigated how the legacies of soil multiple functions left by conversion of
      grassland to agricultural management were mediated by climate warming with a
      reciprocal transplant approach. The overall legacy was further separated into the
      contributions by changes in the abiotic properties of the soil (abiotic process)
      and microbial community (biotic process). We here hypothesized that warming may
      mediate the legacy effects of previous land use, mainly by changing biotic
      processes. Results indicated that warming significantly influenced the total
      legacies of soil respiration and three exoenzyme activities representing
      recalcitrant carbon, nitrogen, and phosphorus cycling, but did not affect the
      total legacy of beta-1,4-glucosidase activity, which is involved in labile carbon
      cycling. The relative contributions of abiotic and biotic processes to the
      warming effects on the total legacy depended on the type of soil function. The
      effects of warming on land use change legacies were derived from altered
      bacterial community structure. The results of the present study suggest that
      climate conditions could interact with land use legacy to determine the ecosystem
      functions in a process-specific way.

PMID- 29367673
TI  - disLocate: tools to rapidly quantify local intermolecular structure to assess two
      dimensional order in self-assembled systems.
AB  - Order classification is particularly important in photonics, optoelectronics,
      nanotechnology, biology, and biomedicine, as self-assembled and living systems
      tend to be ordered well but not perfectly. Engineering sets of experimental
      protocols that can accurately reproduce specific desired patterns can be a
      challenge when (dis)ordered outcomes look visually similar. Robust comparisons
      between similar samples, especially with limited data sets, need a finely tuned
      ensemble of accurate analysis tools. Here we introduce our numerical Mathematica
      package disLocate, a suite of tools to rapidly quantify the spatial structure of
      a two-dimensional dispersion of objects. The full range of tools available in
      disLocate give different insights into the quality and type of order present in a
      given dispersion, accessing the translational, orientational and entropic order.
      The utility of this package allows for researchers to extract the variation and
      confidence range within finite sets of data (single images) using different
      structure metrics to quantify local variation in disorder. Containing all metrics
      within one package allows for researchers to easily and rapidly extract many
      different parameters simultaneously, allowing robust conclusions to be drawn on
      the order of a given system. Quantifying the experimental trends which produce
      desired morphologies enables engineering of novel methods to direct self
      assembly.

PMID- 29367672
TI  - Parallel derivation of isogenic human primed and naive induced pluripotent stem
      cells.
AB  - Induced pluripotent stem cells (iPSCs) have considerably impacted human
      developmental biology and regenerative medicine, notably because they circumvent
      the use of cells of embryonic origin and offer the potential to generate patient
      specific pluripotent stem cells. However, conventional reprogramming protocols
      produce developmentally advanced, or primed, human iPSCs (hiPSCs), restricting
      their use to post-implantation human development modeling. Hence, there is a need
      for hiPSCs resembling preimplantation naive epiblast. Here, we develop a method
      to generate naive hiPSCs directly from somatic cells, using OKMS overexpression
      and specific culture conditions, further enabling parallel generation of their
      isogenic primed counterparts. We benchmark naive hiPSCs against human
      preimplantation epiblast and reveal remarkable concordance in their
      transcriptome, dependency on mitochondrial respiration and X-chromosome status.
      Collectively, our results are essential for the understanding of pluripotency
      regulation throughout preimplantation development and generate new opportunities
      for disease modeling and regenerative medicine.

PMID- 29367674
TI  - Tryptophan hydroxylase (TRH) loss of function mutations induce growth and
      behavioral defects in Daphnia magna.
AB  - Tryptophan hydroxylase (TRH) is the rate limiting enzyme in the serotonin
      synthesis. CRISPR-Cas9 technology was used to generate seven indel TRH mutants in
      Daphnia magna. Mono-allelic indel TRH-/+ clones showed normal levels of
      serotonin, measured by both immunohistochemistry and mass spectrometry (LC
      MS/MS), whereas bi-allelic indel TRH-/- clones showed no detectable levels of
      serotonin. Life history and behavioral responses of TRH-/- clones showed the anti
      phenotype of those exposed to selective serotonin reuptake inhibitors (SSRI).
      Mutants lacking serotonin grew less and hence reproduced latter, produced smaller
      clutches of smaller offspring and responded to a greater extent to light than
      wild type individuals. Mono-allelic indel TRH-/+ individuals showed the
      intermediate phenotype. The SSRI fluoxetine enhanced offspring production in all
      clones and decreased the response to light only in those clones having serotonin,
      thus indication that behavioral effects of this drug in D. magna are associated
      to serotonin. Results obtained with the TRH mutants are in line with reported
      ones in TRH knockouts of Caenorhabditis elegans, Drosophila and mice, indicating
      that there is one gene encoding TRH, which is the serotonin limiting enzyme in
      both the central and the periphery nervous system in Daphnia and that deprivation
      of serotonin increases anxiety-like behavior.

PMID- 29367675
TI  - Vertical Light Sheet Enhanced Side-View Imaging for AFM Cell Mechanics Studies.
AB  - The ability to measure dynamic structural changes within a cell under applied
      load is essential for developing more accurate models of cell mechanics and
      mechanotransduction. Atomic force microscopy is a powerful tool for evaluating
      cell mechanics, but the dominant applied forces and sample strains are in the
      vertical direction, perpendicular to the imaging plane of standard fluorescence
      imaging. Here we report on a combined sideways imaging and vertical light sheet
      illumination system integrated with AFM. Our system enables high frame rate, low
      background imaging of subcellular structural dynamics in the vertical plane
      synchronized with AFM force data. Using our system for cell compression
      measurements, we correlated stiffening features in the force indentation data
      with onset of nuclear deformation revealed in the imaging data. In adhesion
      studies we were able to correlate detailed features in the force data during
      adhesive release events with strain at the membrane and within the nucleus.

PMID- 29367676
TI  - Inhibition of angiogenesis by leflunomide via targeting the soluble ephrin
      A1/EphA2 system in bladder cancer.
AB  - Angiogenesis plays an important role in bladder cancer (BCa). The
      immunosuppressive drug leflunomide has attracted worldwide attention. However,
      the effects of leflunomide on angiogenesis in cancer remain unclear. Here, we
      report the increased expression of soluble ephrin-A1 (sEphrin-A1) in supernatants
      of BCa cell lines (RT4, T24, and TCCSUP) co-cultured with human umbilical vein
      endothelial cells (HUVECs) compared with that in immortalized uroepithelial cells
      (SV-HUC-1) co-cultured with HUVECs. sEphrin-A1 is released from BCa cells as a
      monomeric protein that is a functional form of the ligand. The co-culture
      supernatants containing sEphrin-A1 caused the internalization and down-regulation
      of EphA2 on endothelial cells and dramatic functional activation of HUVECs. This
      sEphrin-A1/EphA2 system is mainly functional in regulating angiogenesis in BCa
      tissue. We showed that leflunomide (LEF) inhibited angiogenesis in a N-butyl-N-(4
      hydroxybutyl)-nitrosamine (BBN)-induced bladder carcinogenesis model and a tumor
      xenograft model, as well as in BCa cell and HUVEC co-culture systems, via
      significant inhibition of the sEphrin-A1/EphA2 system. Ephrin-A1 overexpression
      could partially reverse LEF-induced suppression of angiogenesis and subsequent
      tumor growth inhibition. Thus, LEF has a significant anti-angiogenesis effect on
      BCa cells and BCa tissue via its inhibition of the functional angiogenic sEphrin
      A1/EphA2 system and may have potential for treating BCa beyond immunosuppressive
      therapy.

PMID- 29367677
TI  - Interactive effects of compost and pre-planting soil moisture on plant biomass,
      nutrition and formation of mycorrhizas: a context dependent response.
AB  - We aimed to investigate the combined impacts of compost addition and pre-planting
      soil moisture conditions, on plant-available nutrients, and subsequent impacts on
      the biomass, nutrition and formation of AM by two important crop species. A
      glasshouse study was undertaken in which wheat and tomato plants were grown in
      compost amended or un-amended soil that was subjected to different moisture
      regimes prior to planting. The availability of P was strongly influenced by
      compost addition, but not pre-planting moisture conditions. In contrast, mineral
      N pools were affected by compost addition and pre-planting soil moisture
      conditions in complex ways. These changes in nutrient availability affected plant
      biomass, nutrient uptake and formation of AM. In general, plant performance was
      better where pre-planting soil moisture conditions were wet or dry, and worse
      where they involved a wet/dry cycle, and mycorrhizal colonisation was lower where
      compost was added to the soil. That pre-planting moisture conditions affect the
      biomass of subsequent crops is an important finding, the potential implications
      of which are considered here.

PMID- 29367678
TI  - Publisher Correction: The burden and challenges of tuberculosis in China:
      findings from the Global Burden of Disease Study 2015.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29367679
TI  - Multilocus Sequence Typing Reveals both Shared and Unique Genotypes of
      Cryptococcus neoformans in Jiangxi Province, China.
AB  - Cryptococcosis is a globally distributed infectious fungal disease. However, much
      remains unknown about its molecular epidemiology in many parts of the world. In
      this study, we analyzed 86 clinical Cryptococcus neoformans isolates from 14
      regions in Jiangxi Province in south central China. Each isolate was from a
      different patient and 35 of the 86 (40.7%) patients were infected with HIV. All
      strains belonged to serotype A and mating type alpha (MATalpha). Genotyping based
      on DNA sequences at seven nuclear loci revealed eight sequence types (STs) among
      the 86 isolates, including two novel STs that have not been reported from other
      parts of the world. ST5 was the dominant genotype and our comparative analyses
      showed that these genotypes in Jiangxi likely originated by dispersal from other
      regions within and outside of China and/or mutations from another genotype within
      Jiangxi. Though none of the isolates was resistant to the five tested antifungal
      drugs (flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole),
      obvious differences in their minimum inhibitory concentrations were observed,
      even among isolates of the same ST. Our results suggest that continuous
      monitoring should be conducted to understand the changing dynamics of C.
      neoformans in this and other regions.

PMID- 29367681
TI  - Two types of weight-dependent walks with a trap in weighted scale-free treelike
      networks.
AB  - In this paper, we present the weighted scale-free treelike networks controlled by
      the weight factor r and the parameter m. Based on the network structure, we study
      two types of weight-dependent walks with a highest-degree trap. One is standard
      weight-dependent walk, while the other is mixed weight-dependent walk including
      both nearest-neighbor and next-nearest-neighbor jumps. Although some properties
      have been revealed in weighted networks, studies on mixed weight-dependent walks
      are still less and remain a challenge. For the weighted scale-free treelike
      network, we derive exact solutions of the average trapping time (ATT) measuring
      the efficiency of the trapping process. The obtained results show that ATT is
      related to weight factor r, parameter m and spectral dimension of the weighted
      network. We find that in different range of the weight factor r, the leading term
      of ATT grows differently, i.e., superlinearly, linearly and sublinearly with the
      network size. Furthermore, the obtained results show that changing the walking
      rule has no effect on the leading scaling of the trapping efficiency. All results
      in this paper can help us get deeper understanding about the effect of link
      weight, network structure and the walking rule on the properties and functions of
      complex networks.

PMID- 29367680
TI  - Olfactory receptors are expressed in pancreatic beta-cells and promote glucose
      stimulated insulin secretion.
AB  - Olfactory receptors (ORs) mediate olfactory chemo-sensation in OR neurons.
      Herein, we have demonstrated that the OR chemo-sensing machinery functions in
      pancreatic beta-cells and modulates insulin secretion. First, we found several OR
      isoforms, including OLFR15 and OLFR821, to be expressed in pancreatic islets and
      a beta-cell line, MIN6. Immunostaining revealed OLFR15 and OLFR821 to be
      uniformly expressed in pancreatic beta-cells. In addition, mRNAs of Olfr15 and
      Olfr821 were detected in single MIN6 cells. These results indicate that multiple
      ORs are simultaneously expressed in individual beta-cells. Octanoic acid, which
      is a medium-chain fatty acid contained in food and reportedly interacts with
      OLFR15, potentiated glucose-stimulated insulin secretion (GSIS), thereby
      improving glucose tolerance in vivo. GSIS potentiation by octanoic acid was
      confirmed in isolated pancreatic islets and MIN6 cells and was blocked by OLFR15
      knockdown. While Galpha olf expression was not detectable in beta-cells,
      experiments using inhibitors and siRNA revealed that the pathway dependent on
      phospholipase C-inositol triphosphate, rather than cAMP-protein kinase A,
      mediates GSIS potentiation via OLFR15. These findings suggest that the OR system
      in pancreatic beta-cells has a chemo-sensor function allowing recognition of
      environmental substances obtained from food, and potentiates insulin secretion in
      a cell-autonomous manner, thereby modulating systemic glucose metabolism.

PMID- 29367682
TI  - Activation of Activin receptor-like kinases curbs mucosal inflammation and
      proliferation in chronic rhinosinusitis with nasal polyps.
AB  - Chronic rhinosinusitis with nasal polyps (CRSwNP) is a widespread disease causing
      obstruction of the nasal cavity. Its cause remains unclear. The transforming
      growth-factor beta (TGF-beta) superfamily and their receptors, termed Activin
      receptor-like kinases (ALKs), have recently been suggested to play a role in
      local airway inflammation, but have so far not been evaluated in human nasal
      epithelial cells (HNECs) from CRSwNP patients. We demonstrated that ALK1-7 were
      expressed in the nasal polyp epithelium, and the expression of ALK1-6 was
      markedly elevated in polyps compared to nasal mucosa from healthy controls.
      Stimulation with the ALK ligand TGF-beta1 decreased Ki67 expression in HNECs from
      CRSwNP patients, not evident in controls. Likewise, TGF-beta1, Activin A and
      Activin B, all ALK ligands, decreased IL-8 release and Activin A and Activin B
      reduced ICAM1 expression on HNECs from CRSwNP patients, not seen in controls. Pre
      stimulation with TGF-beta1, Activin A, BMP4 and Activin B attenuated a TNF-alpha
      induced ICAM1 upregulation on HNECs of CRSwNP. No effect was evident in controls.
      In conclusion, an increased expression of ALK1-6 was found on polyp epithelial
      cells and ligand stimulation appeared to reduce proliferation and local
      inflammation in polyps.

PMID- 29367683
TI  - Staphylococcal LTA antagonizes the B cell-mitogenic potential of LPS.
AB  - Lipoteichoic acid (LTA) of Gram-positive bacteria is regarded as the counterpart
      biomolecule of lipopolysaccharide (LPS) of Gram-negative bacteria because of
      their structural and immunological similarities. Although LPS induces a strong
      polyclonal expansion of B cells, little is known about the effect of LTA on B
      cell proliferation. In the present study, we prepared LTAs from Gram-positive
      bacteria and examined their effect on splenic B cell proliferation. Unlike LPS,
      LTA did not induce B cell proliferation. Instead, Staphylococcus aureus LTA
      (Sa.LTA) appeared to inhibit LPS-induced B cell proliferation in vitro, ex vivo,
      and in vivo models. Such effect was observed neither in splenocytes from Toll
      like receptor 2 (TLR2)-deficient mice nor in the purified splenic B cells.
      Furthermore, decreased ERK phosphorylation appeared to be responsible for this
      phenomenon. Collectively, our results support that Sa.LTA inhibited LPS-induced B
      cell proliferation through the decrease of ERK phosphorylation via TLR2 signaling
      pathway.

PMID- 29367684
TI  - Perovskite Thin Film Synthesised from Sputtered Lead Sulphide.
AB  - In the last few years, research on dye-sensitised devices has been focused on the
      development of solar cells, based on CH3NH3PbX3 (X = I-, Br-, Cl-) composites
      with perovskite structure. The deposition of perovskite thin films is usually
      carried out by solution-based processes using spin-coating techniques that result
      in the production of high quality films. Solar cells made by this method exceed
      20% efficiency, with the potential for use in large scale production through ink
      print or screen printing techniques. As an alternative route, perovskite thin
      films can be deposited through thermal evaporation. A new method is proposed to
      produce CH3NH3PbI3, based on a radio-frequency (rf) -sputtering technique that
      results in a high reproducibility of the films and is compatible with roll-to
      roll processes. We deposited thin films of lead-sulphide (PbS) and converted them
      into perovskite by placing the films in an iodine atmosphere, followed by dipping
      in a solution of methylammonium iodide (CH3NH3I). The conversions to PbI2 and
      CH3NH3PbI3 were confirmed by elemental analyses, absorption, and
      photoluminescence spectroscopy. Structural properties were revealed by X-ray
      diffraction and infrared and Raman spectroscopy.

PMID- 29367685
TI  - In vivo imaging of adeno-associated viral vector labelled retinal ganglion cells.
AB  - A defining characteristic of optic neuropathies, such as glaucoma, is progressive
      loss of retinal ganglion cells (RGCs). Current clinical tests only provide weak
      surrogates of RGC loss, but the possibility of optically visualizing RGCs and
      quantifying their rate of loss could represent a radical advance in the
      management of optic neuropathies. In this study we injected two different adeno
      associated viral (AAV) vector serotypes in the vitreous to enable green
      fluorescent protein (GFP) labelling of RGCs in wild-type mice for in vivo and non
      invasive imaging. GFP-labelled cells were detected by confocal scanning laser
      ophthalmoscopy 1-week post-injection and plateaued in density at 4 weeks.
      Immunohistochemical analysis 5-weeks post-injection revealed labelling
      specificity to RGCs to be significantly higher with the AAV2-DCX-GFP vector
      compared to the AAV2-CAG-GFP vector. There were no adverse functional or
      structural effects of the labelling method as determined with electroretinography
      and optical coherence tomography, respectively. The RGC-specific positive and
      negative scotopic threshold responses had similar amplitudes between control and
      experimental eyes, while inner retinal thickness was also unchanged after
      injection. As a positive control experiment, optic nerve transection resulted in
      a progressive loss of labelled RGCs. AAV vectors provide strong and long-lasting
      GFP labelling of RGCs without detectable adverse effects.

PMID- 29367687
TI  - The association between short-term response and long-term survival for cervical
      cancer patients undergoing neoadjuvant chemotherapy: a system review and meta
      analysis.
AB  - Controversy exists regarding whether a short-term response has an impact on the
      long-term survival of cervical cancer patients undergoing neoadjuvant
      chemotherapy (NACT). This study was designed to identify the predictive role of
      an early response by pooling the results of previous studies. The PubMed and
      Embase databases were searched through July 2016, and the associations between an
      early response and disease-free survival (DFS) were pooled by hazard ratio (HR)
      using random effects models. Six studies involving 490 cervical cancer patients,
      with 336 responders and 154 non-responders, were finally included in the meta
      analysis. The HR for 1-year DFS between early responders and non-responders was
      0.25 (95% CI 0.10-0.58, P = 0.001). The HRs for 2-, 3-, 4-, and 5-year DFS were
      0.28 (95% CI 0.15-0.56), 0.27 (95% CI 0.16-0.45), 0.29 (95% CI 0.17-0.50) and
      0.33 (95% CI 0.20-0.54), respectively. No obvious heterogeneity was found among
      the studies, with I2 = 0, and a sensitivity analysis showed that all pooled
      results were robust with logHR confidence limits < 0. An early response was
      associated with DFS, and responders achieved a significantly higher survival rate
      than non-responders. This finding should be validated in future prospective
      studies.

PMID- 29367686
TI  - Palisade cell shape affects the light-induced chloroplast movements and leaf
      photosynthesis.
AB  - Leaf photosynthesis is regulated by multiple factors that help the plant to adapt
      to fluctuating light conditions. Leaves of sun-light-grown plants are thicker and
      contain more columnar palisade cells than those of shade-grown plants. Light
      induced chloroplast movements are also essential for efficient leaf
      photosynthesis and facilitate efficient light utilization in leaf cells. Previous
      studies have demonstrated that leaves of most of the sun-grown plants exhibited
      no or very weak chloroplast movements and could accomplish efficient
      photosynthesis under strong light. To examine the relationship between palisade
      cell shape, chloroplast movement and distribution, and leaf photosynthesis, we
      used an Arabidopsis thaliana mutant, angustifolia (an), which has thick leaves
      that contain columnar palisade cells similar to those in the sun-grown plants. In
      the highly columnar cells of an mutant leaves, chloroplast movements were
      restricted. Nevertheless, under white light condition (at 120 umol m-2 s-1), the
      an mutant plants showed higher chlorophyll content per unit leaf area and, thus,
      higher light absorption by the leaves than the wild type, which resulted in
      enhanced photosynthesis per unit leaf area. Our findings indicate that
      coordinated regulation of leaf cell shape and chloroplast movement according to
      the light conditions is pivotal for efficient leaf photosynthesis.

PMID- 29367688
TI  - Mitral valve annuloplasty versus replacement for severe ischemic mitral
      regurgitation.
AB  - Although practice guidelines recommend surgery for patients with severe chronic
      ischemic mitral regurgitation (CIMR), they do not specify whether to repair or
      replace the mitral valve. 436 consecutive patients with severe CIMR were eligible
      for inclusion in the study, of which 316 (72.5%) underwent mitral valve
      annuloplasty (MVA) whereas 120 (27.5%) received mitral valve replacement (MVR).
      At 59 months (interquartile range, 37-85 months) follow-up, though the left
      ventricle end-diastolic diameter was markedly larger (P = 0.019) in the MVA group
      than in the MVR group, no significant difference was observed in overall
      survival, freedom from cardiac death, or avoidance of major adverse cardiac or
      cerebrovascular events (MACCE). MVA provides better results in freedom from
      cardiac death in subgroups of age >=65years and left ventricular ejection
      fraction (EF) >=50% (P = 0.014 and P = 0.016, respectively), whereas MVR was
      associated with a lower risk of MACCE in subgroups of age <65years, EF <50% and
      left ventricular inferior basal wall motion abnormality (BWMA) (all P < 0.05). In
      conclusion, MVR is a suitable management of patients with severe CIMR, and it is
      more favorable to ventricular remodeling. The choice of MVA or MVR should depend
      on major high-risk clinical factors.

PMID- 29367690
TI  - Spondyloarthritis: Low-dose CT for spondyloarthritis - a brilliant new chapter?

PMID- 29367689
TI  - Repression of Akt3 gene transcription by the tumor suppressor RIZ1.
AB  - RIZ1 has been studied as a tumor suppressor and may play a role in metabolic
      diseases related to the Western style diet, such as cancer and obesity. The Akt
      pathway is known to play a role in both cancer and obesity, and a link between
      Akt and RIZ1 has also been found. To better understand the role of RIZ1 in
      obesity and cancer, we investigated how RIZ1 regulates the expression of Akt3. We
      found that overexpression of RIZ1 in HEK293 cells reduced the expression of Akt3
      protein. Luciferase reporter activity of Akt3 gene promoter was significantly
      reduced in cells co-transfected with RIZ1. Recombinant proteins of RIZ1 was able
      to bind the Akt3 promoter in vitro, and chromatin immunoprecipitation assay also
      demonstrated the ability of RIZ1 binding to the Akt3 promoter in vivo.
      Overexpression of RIZ1 increased H3K9 methylation on the Akt3 promoter. These
      results identify Akt3 as a target of RIZ1 regulation and expand our understanding
      of the Akt pathway in cancer and obesity.

PMID- 29367691
TI  - Osteoporosis: Romosozumab to rebuild the foundations of bone strength.

PMID- 29367692
TI  - Systemic lupus erythematosus: Stress and the onset of SLE.

PMID- 29367693
TI  - HMG-box transcription factor 1: a positive regulator of the G1/S transition
      through the Cyclin-CDK-CDKI molecular network in nasopharyngeal carcinoma.
AB  - HMG-box transcription factor 1 (HBP1) has been reported to be a tumor suppressor
      in diverse malignant carcinomas. However, our findings provide a conclusion that
      HBP1 plays a novel role in facilitating nasopharyngeal carcinoma (NPC) growth.
      The Kaplan-Meier analysis indicates that high expression HBP1 and low miR-29c
      expression both are negatively correlated with the overall survival rates of NPC
      patients. HBP1 knockdown inhibits cellular proliferation and growth, and arrested
      cells in G1 phase rather than affected cell apoptosis via flow cytometry (FCM)
      analysis. Mechanistically, HBP1 induces the expression of CCND1 and CCND3 levels
      by binding to their promoters, and binds to CDK4, CDK6 and p16INK4A promoters
      while not affects their expression levels. CCND1 and CCND3 promote CCND1-CDK4,
      CCND3-CDK6, and CDK2-CCNE1 complex formation, thus, E2F-1 and DP-1 are activated
      to accelerate the G1/S transition in the cell cycle. MiR-29c is down-regulated
      and correlated with NPC tumorigenesis and progression. Luciferase assays confirms
      that miR-29c binds to the 3' untranslated region (3'-UTR) of HBP1. Introduction
      of pre-miR-29c decreased HBP1 mRNA and protein levels. Therefore, the high
      endogenous HBP1 expression might be attributed to the low levels of endogenous
      miR-29c in NPC. In addition, HBP1 knockdown and miR-29c agomir administration
      both decrease xenograft growth in nude mice in vivo. It is firstly reported that
      HBP1 knockdown inhibited the proliferation and metastasis of NPC, which indicates
      that HBP1 functions as a non-tumor suppressor gene in NPC. This study provides a
      novel potential target for the prevention of and therapies for NPC.

PMID- 29367694
TI  - The Arabidopsis NLP7 gene regulates nitrate signaling via NRT1.1-dependent
      pathway in the presence of ammonium.
AB  - Nitrate is not only an important nutrient but also a signaling molecule for
      plants. A few of key molecular components involved in primary nitrate responses
      have been identified mainly by forward and reverse genetics as well as systems
      biology, however, many underlining mechanisms of nitrate regulation remain
      unclear. In this study, we show that the expression of NRT1.1, which encodes a
      nitrate sensor and transporter (also known as CHL1 and NPF6.3), is modulated by
      NIN-like protein 7 (NLP7). Genetic and molecular analyses indicate that NLP7
      works upstream of NRT1.1 in nitrate regulation when NH4+ is present, while in
      absence of NH4+, it functions in nitrate signaling independently of NRT1.1.
      Ectopic expression of NRT1.1 in nlp7 resulted in partial or complete restoration
      of nitrate signaling (expression from nitrate-regulated promoter NRP), nitrate
      content and nitrate reductase activity in the transgenic lines. Transcriptome
      analysis revealed that four nitrogen-related clusters including amino acid
      synthesis-related genes and members of NRT1/PTR family were modulated by both
      NLP7 and NRT1.1. In addition, ChIP and EMSA assays results indicated that NLP7
      may bind to specific regions of the NRT1.1 promoter. Thus, NLP7 acts as an
      important factor in nitrate signaling via regulating NRT1.1 under NH4+
      conditions.

PMID- 29367695
TI  - High diversity and abundance of cultivable tetracycline-resistant bacteria in
      soil following pig manure application.
AB  - By performing a microcosm experiment mimicking fertilization, we assessed the
      dynamic distribution of tetracycline-resistant bacteria (TRB) and corresponding
      tetracycline resistance genes (TRGs) from pig manure (PM) to the fertilized soil,
      by culture-dependent methods and PCR detection. Cultivable TRB were most abundant
      in PM, followed by fertilized soil and unfertilized soil. By restriction fragment
      length polymorphism (RFLP) analysis, TRB were assigned to 29, 20, and 153
      operational taxonomic units (OTUs) in PM, unfertilized soil, and fertilized soil,
      respectively. After identification, they were further grouped into 19, 12, and 62
      species, showing an enhanced diversity of cultivable TRB in the soil following PM
      application. The proportions of potentially pathogenic TRB in fertilized soil
      decreased by 69.35% and 41.92% compared with PM and unfertilized soil. Bacillus
      cereus was likely widely distributed TRB under various environments, and
      Rhodococcus erythropolis and Acinetobacter sp. probably spread from PM to the
      soil via fertilization. Meanwhile, tetL was the most common efflux pump gene in
      both unfertilized and fertilized soils relative to PM; tetB(P) and tet36 were
      common in PM, whereas tetO was predominant in unfertilized and fertilized soil
      samples. Sequencing indicated that over 65% of randomly selected TRB in
      fertilized soil with acquired resistance derived from PM.

PMID- 29367696
TI  - Social Engagement and Its Change are Associated with Dementia Risk among Chinese
      Older Adults: A Longitudinal Study.
AB  - This study aimed to examine the association of social engagement (SE) and changes
      in SE with the risk of dementia among older adults in China. Data were collected
      from the 2002, 2005, 2008/2009, and 2011/2012 waves of the Chinese Longitudinal
      Healthy Longevity Survey (CLHLS). Random-effects logistic regression models were
      used to examine the association of SE and changes in SE with the risk of
      dementia. Of the 7511 older Chinese adults aged 65 years and over, 338 developed
      dementia during the 9-year follow-up. SE was associated with dementia risk after
      adjusting for sociodemographic characteristics, lifestyles and health status
      (odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.63-0.81). Participants
      with consistently high or increased SE had a lower risk of dementia than those
      with consistently low SE ((OR = 0.14, 95% CI = 0.06-0.28 and OR = 0.33, 95% CI =
      0.23-0.48, respectively). Higher SE can reduce the risk of dementia. Furthermore,
      consistently high or increasing SE is associated with a lower risk of dementia.

PMID- 29367697
TI  - Identification of microRNA signature in the progression of gestational
      trophoblastic disease.
AB  - Gestational trophoblastic disease (GTD) encompasses a range of trophoblast
      derived disorders. The most common type of GTD is hydatidiform mole (HM). Some of
      HMs can further develop into malignant gestational trophoblastic neoplasia (GTN).
      Aberrant expression of microRNA (miRNA) is widely reported to be involved in the
      initiation and progression of cancers. MiRNA expression profile also has been
      proved to be the useful signature for diagnosis, staging, prognosis, and response
      to chemotherapy. Till now, the profile of miRNA in the progression of GTD has not
      been determined. In this study, a total of 34 GTN and 60 complete HMs (CHM)
      trophoblastic tissues were collected. By miRNA array screening and qRT-PCR
      validating, six miRNAs, including miR-370-3p, -371a-5p, -518a-3p, -519d-3p, -520a
      3p, and -934, were identified to be differentially expressed in GTN vs. CHM.
      Functional analyses further proved that miR-371a-5p and miR-518a-3p promoted
      proliferation, migration, and invasion of choriocarcinoma cells. Moreover, we
      demonstrated that miR-371a-5p was negatively related to protein levels of its
      predictive target genes BCCIP, SOX2, and BNIP3L, while miR-518a-3p was negatively
      related to MST1 and EFNA4. For the first time, we proved that miR-371a-5p and miR
      518a-3p directly targeted to 3'-UTR regions of BCCIP and MST1, respectively.
      Additionally, we found that miR-371a-5p and miR-518a-3p regulated diverse
      pathways related to tumorigenesis and metastasis in choriocarcinoma cells. The
      results presented here may offer new clues to the progression of GTD and may
      provide diagnostic biomarkers for GTN.

PMID- 29367698
TI  - The Lewis A phenotype is a restriction factor for Rotateq and Rotarix vaccine
      take in Nicaraguan children.
AB  - Histo-blood group antigens (HBGAs) and the Lewis and secretor antigens are
      associated with susceptibility to rotavirus infection in a genotype-dependent
      manner. Nicaraguan children were prospectively enrolled in two cohorts vaccinated
      with either RotaTeq RV5 (n = 68) or Rotarix RV1 (n = 168). Lewis and secretor
      antigens were determined by saliva phenotyping and genotyping. Seroconversion was
      defined as a 4-fold increase in plasma IgA antibody titer 1 month after
      administration of the first dose of the vaccine. Regardless of the vaccine
      administered, significantly fewer of the children with Lewis A phenotype (0/14)
      seroconverted after receiving the first vaccine dose compared to 26% (45/175) of
      those with the Lewis B phenotype and 32% (15/47) of the Lewis negative
      individuals (P < 0.01). Furthermore, following administration of the RV1 vaccine,
      secretor-positive ABO blood group B children seroconverted to a significantly
      lesser extent (5%) compared to secretor-positive children with ABO blood groups A
      (26%) and O (27%) (P < 0.05). Other factors such as pre-vaccination titers, sex,
      breastfeeding, and calprotectin levels did not influence vaccine-take.
      Differences in HBGA expression appear to be a contributing factor in the
      discrepancy in vaccine-take and thus, in vaccine efficacy in different ethnic
      populations.

PMID- 29367699
TI  - Plastid phylogenomics with broad taxon sampling further elucidates the distinct
      evolutionary origins and timing of secondary green plastids.
AB  - Secondary plastids derived from green algae occur in chlorarachniophytes,
      photosynthetic euglenophytes, and the dinoflagellate genus Lepidodinium. Recent
      advances in understanding the origin of these plastids have been made, but
      analyses suffer from relatively sparse taxon sampling within the green algal
      groups to which they are related. In this study we aim to derive new insights
      into the identity of the plastid donors, and when in geological time the
      independent endosymbiosis events occurred. We use newly sequenced green algal
      chloroplast genomes from carefully chosen lineages potentially related to
      chlorarachniophyte and Lepidodinium plastids, combined with recently published
      chloroplast genomes, to present taxon-rich phylogenetic analyses to further
      pinpoint plastid origins. We integrate phylogenies with fossil information and
      relaxed molecular clock analyses. Our results indicate that the
      chlorarachniophyte plastid may originate from a precusor of siphonous green algae
      or a closely related lineage, whereas the Lepidodinium plastid originated from a
      pedinophyte. The euglenophyte plastid putatively originated from a lineage of
      prasinophytes within the order Pyramimonadales. Our molecular clock analyses
      narrow in on the likely timing of the secondary endosymbiosis events, suggesting
      that the event leading to Lepidodinium likely occurred more recently than those
      leading to the chlorarachniophyte and photosynthetic euglenophyte lineages.

PMID- 29367700
TI  - Optimization reconstruction method of object profile using flexible laser plane
      and bi-planar references.
AB  - An optimization method to reconstruct the object profile is performed by using a
      flexible laser plane and bi-planar references. The bi-planar references are
      considered as flexible benchmarks to realize the transforms among two world
      coordinate systems on the bi-planar references, the camera coordinate system and
      the image coordinate system. The laser plane is confirmed by the intersection
      points between the bi-planar references and laser plane. The 3D camera
      coordinates of the intersection points between the laser plane and a measured
      object are initially reconstructed by the image coordinates of the intersection
      points, the intrinsic parameter matrix and the laser plane. Meanwhile, an
      optimization function is designed by the parameterized differences of the
      reconstruction distances with the help of a target with eight markers, and the
      parameterized reprojection errors of feature points on the bi-planar references.
      The reconstruction method with the bi-planar references is evaluated by the
      difference comparisons between true distances and standard distances. The mean of
      the reconstruction errors of the initial method is 1.01 mm. Moreover, the mean of
      the reconstruction errors of the optimization method is 0.93 mm. Therefore, the
      optimization method with the bi-planar references has great application prospects
      in the profile reconstruction.

PMID- 29367701
TI  - Induced neural stem cell-derived astrocytes modulate complement activation and
      mediate neuroprotection following closed head injury.
AB  - The complement system is a crucial component of immunity, and its activation has
      critical roles in neuroinflammatory response and cellular damage following closed
      head injury (CHI). We previously demonstrated that systemically injected induced
      neural stem cells (iNSCs) could modulate complement activation to ameliorate
      neuronal apoptosis in mouse CHI models. However, it remains unknown whether iNSC
      derivatives can regulate complement activation. In the present study, after CHI
      mouse serum treatment, we found dramatic decreases in the cellular viabilities of
      differentiated iNSCs. Interestingly, following CHI mouse serum treatment, the
      death of astrocytes derived from iNSCs which were pre-treated with CHI mouse
      serum was significantly decreased. Meanwhile, the deposition of C3 (C3d) and C5b
      9 in these astrocytes was substantially reduced. Remarkably, we detected
      increased expression of complement receptor type 1-related protein y (Crry) in
      these astrocytes. Moreover, these astrocytes could reduce the numbers of
      apoptotic neurons via Crry expression post-CHI mouse serum treatment.
      Additionally, intracerebral-transplanted iNSCs, pre-treated with CHI mouse serum,
      significantly increased the levels of Crry expression in astrocytes to reduce the
      accumulation of C3d and C9 and the death of neurons in the brains of CHI mice. In
      summary, iNSCs receiving CHI mouse serum pre-treatment could enhance the
      expression of Crry in iNSC-derived astrocytes to modulate complement activation
      and mediate neuroprotection following CHI.

PMID- 29367703
TI  - In vivo fluorescence bioimaging of ascorbic acid in mice: Development of an
      efficient probe consisting of phthalocyanine, TEMPO, and albumin.
AB  - After a groundbreaking study demonstrated that a high dose of ascorbic acid
      selectively kills cancer cells, the compound has been tested in the clinic
      against various forms of cancers, with some success. However, in vivo tracing of
      intravenously injected ascorbic acid has not been achieved. Herein, we
      successfully imaged ascorbic acid intravenously injected into mice based on the
      discovery of a novel, highly sensitive, and appropriately selective fluorescent
      probe consisting of silicon phthalocyanine (SiPc) and two 2,2,6,6-tetramethyl-1
      piperidinyloxy (TEMPO) radicals, i.e., R2c. The radicals in this R2c were
      encapsulated in dimeric bovine serum albumin, and the sensitivity was >100-fold
      higher than those of other R2c-based probes. Ascorbic acid intravenously injected
      into mice was efficiently transported to the liver, heart, lung, and cholecyst.
      The present results provide opportunities to advance the use of ascorbic acid as
      cancer therapy.

PMID- 29367702
TI  - Angiogenic factor-driven inflammation promotes extravasation of human
      proangiogenic monocytes to tumours.
AB  - Recruitment of circulating monocytes is critical for tumour angiogenesis.
      However, how human monocyte subpopulations extravasate to tumours is unclear.
      Here we show mechanisms of extravasation of human CD14dimCD16+ patrolling and
      CD14+CD16+ intermediate proangiogenic monocytes (HPMo), using human tumour
      xenograft models and live imaging of transmigration. IFNgamma promotes an
      increase of the chemokine CX3CL1 on vessel lumen, imposing continuous crawling to
      HPMo and making these monocytes insensitive to chemokines required for their
      extravasation. Expression of the angiogenic factor VEGF and the inflammatory
      cytokine TNF by tumour cells enables HPMo extravasation by inducing GATA3
      mediated repression of CX3CL1 expression. Recruited HPMo boosts angiogenesis by
      secreting MMP9 leading to release of matrix-bound VEGF-A, which amplifies the
      entry of more HPMo into tumours. Uncovering the extravasation cascade of HPMo
      sets the stage for future tumour therapies.

PMID- 29367704
TI  - Association of metreleptin treatment and dietary intervention with neurological
      outcomes in Celia's encephalopathy.
AB  - Celia's encephalopathy (progressive encephalopathy with/without lipodystrophy,
      PELD) is a recessive neurodegenerative disease that is fatal in childhood. It is
      caused by a c.985C>T variant in the BSCL2/seipin gene that results in an aberrant
      seipin protein. We evaluated neurological development before and during treatment
      with human recombinant leptin (metreleptin) plus a dietary intervention rich in
      polyunsaturated fatty acids (PUFA) in the only living patient. A 7 years and 10
      months old girl affected by PELD was treated at age 3 years with metreleptin,
      adding at age 6 omega-3 fatty acid supplementation. Her mental age was evaluated
      using the Battelle Developmental Inventory Screening Test (BDI), and brain
      PET/MRI was performed before treatment and at age 5, 6.5, and 7.5 years. At age
      7.5 years, the girl remains alive and leads a normal life for her mental age of
      30 months, which increased by 4 months over the last 18 months according to BDI.
      PET images showed improved glucose uptake in the thalami, cerebellum, and
      brainstem. This patient showed a clear slowdown in neurological regression during
      leptin replacement plus a high PUFA diet. The aberrant BSCL2 transcript was
      overexpressed in SH-SY5Y cells and was treated with docosahexaenoic acid (200 uM)
      plus leptin (0.001 mg/ml) for 24 h. The relative expression of aberrant BSCL2
      transcript was measured by qPCR. In vitro studies showed significant reduction
      (32%) in aberrant transcript expression. This therapeutic approach should be
      further studied in this devastating disease.

PMID- 29367705
TI  - Somatic APC mosaicism and oligogenic inheritance in genetically unsolved
      colorectal adenomatous polyposis patients.
AB  - Germline variants in the APC gene cause familial adenomatous polyposis. Inherited
      variants in MutYH, POLE, POLD1, NTHL1, and MSH3 genes and somatic APC mosaicism
      have been reported as alternative causes of polyposis. However, ~30-50% of cases
      of polyposis remain genetically unsolved. Thus, the aim of this study was to
      investigate the genetic causes of unexplained adenomatous polyposis. Eight
      sporadic cases with >20 adenomatous polyps by 35 years of age or >50 adenomatous
      polyps by 55 years of age, and no causative germline variants in APC and/or
      MutYH, were enrolled from a cohort of 56 subjects with adenomatous colorectal
      polyposis. APC gene mosaicism was investigated on DNA from colonic adenomas by
      Sanger sequencing or Whole Exome Sequencing (WES). Mosaicism extension to other
      tissues (peripheral blood, saliva, hair follicles) was evaluated using Sanger
      sequencing and/or digital PCR. APC second hit was investigated in adenomas from
      mosaic patients. WES was performed on DNA from peripheral blood to identify
      additional polyposis candidate variants. We identified APC mosaicism in 50% of
      patients. In three cases mosaicism was restricted to the colon, while in one it
      also extended to the duodenum and saliva. One patient without APC mosaicism,
      carrying an APC in-frame deletion of uncertain significance, was found to harbor
      rare germline variants in OGG1, POLQ, and EXO1 genes. In conclusion, our
      restrictive selection criteria improved the detection of mosaic APC patients. In
      addition, we showed for the first time that an oligogenic inheritance of rare
      variants might have a cooperative role in sporadic colorectal polyposis onset.

PMID- 29367706
TI  - Human beta defensin (HBD) gene copy number affects HBD2 protein levels: impact on
      cervical bactericidal immunity in pregnancy.
AB  - Human beta defensin 2 (HBD2) is an endogenous mucosal antimicrobial peptide (AMP)
      upregulated during infection and inflammation. HBD2 is encoded by the DEFB4 gene,
      which exhibits extensive copy number variation. Previous studies have
      demonstrated a relationship between HBD copy number and serum HBD2 protein
      levels; however, our current understanding of the influence of copy number on
      mucosal AMP function remains limited. This study explores the relationship
      between HBD copy number, cervicovaginal HBD2 protein levels and antimicrobial
      activity in 203 women with risk factors for preterm birth. We provide evidence
      that suggests HBD copy number modulates cervical antimicrobial immunity.

PMID- 29367708
TI  - Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease.
AB  - Inhibition of the Janus-associated kinases (JAK) with ruxolitinib (RUX) reduces
      graft-versus-host disease (GVHD) in preclinical and clinical models. In total 19
      allograft recipients with moderate/severe steroid-dependent chronic GVHD received
      RUX as >=2nd line salvage. RUX was well tolerated, and led to complete/partial
      resolution of oral (92/7%), cutaneous (82/0%), hepatic (71/28%), gastro
      intestinal (75/17%), musculoskeletal (33/67%), pulmonary (0/80%), scleroderma
      (0/75%), vaginal (0/75%), and ocular (0/100%) chronic GVHD. Overall 18 achieved
      partial response and 1 complete response according to NIH Consensus Criteria.
      Responses occurred early and were sustained which enabled discontinuation (68%)
      or reduction of steroids to physiologic doses (21%). We conclude that RUX is an
      effective steroid-sparing agent in chronic GVHD.

PMID- 29367707
TI  - Cost of cancer diagnosis using next-generation sequencing targeted gene panels in
      routine practice: a nationwide French study.
AB  - It is currently unclear if next-generation sequencing (NGS) technologies can be
      implemented in the diagnosis setting at an affordable cost. The aim of this study
      was to measure the total cost of performing NGS in clinical practice in France,
      in both germline and somatic cancer genetics.The study was performed on 15 French
      representative cancer molecular genetics laboratories performing NGS panels'
      tests. The production cost was estimated using a micro-costing method with
      resources consumed collected in situ in each laboratory from a healthcare
      provider perspective. In addition, we used a top-down methodology for specific
      post-sequencing steps including bioinformatics, technical validation, and
      biological validation. Additional non-specific costs were also included. Costs
      were detailed per step of the process (from the pre-analytical phase to delivery
      of results), and per cost driver (consumables, staff, equipment, maintenance,
      overheads). Sensitivity analyses were performed.The mean total cost of NGS for
      targeted gene panels was estimated to 607? (+/-207) in somatic genetics and 550?
      (+/-140) in germline oncogenetic analysis. Consumables were the highest cost
      driver of the sequencing process. The sensitivity analysis showed that a 25%
      reduction of consumables resulted in a 15% decrease in total NGS cost in somatic
      genetics, and 13% in germline analysis. Additional costs accounted for 30-32% of
      the total NGS costs.Beyond cost assessment considerations, the diffusion of NGS
      technologies will raise questions about their efficiency when compared to more
      targeted approaches, and their added value in a context of routine diagnosis.

PMID- 29367710
TI  - The Japan Marrow Donor Program, 25 years of experience in achieving 20,000 bone
      marrow transplantations: organization structure, activity, and financial basis.
AB  - The Japan Marrow Donor Program (JMDP), established in 1991, has continued to grow
      in its capacity to facilitate unrelated bone marrow (BMT) and peripheral blood
      stem cell transplantation (PBSCT) for the past 25 years in Japan. The current
      donor pool is 463,465 (as of 31 December 2016) and 20,237 transplants were
      performed with the help of the Japanese Red Cross, government, and supporters. As
      JMDP introduced PBSCT in 2010, the vast majority of transplants are BMT. All
      donors are fully typed for HLA-A, B, C, and DR. The peak age of registered donors
      is around 40 years. The 8/8 HLA-matched donors are found in our registry for 96%
      of the patients and 54% of the patients receive a transplant. The median time
      between the initiation of donor search and the transplantation is approximately
      122 days. The median interval between the initiation of donor search and
      identification of the first potential donor is 40 days. The most common diseases
      for which unrelated BMT/PBSCT is indicated are acute myelogenous leukemia (AML),
      acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), and malignant
      lymphoma. In recent years we have seen a marked increase in elderly patients who
      received BMT.

PMID- 29367709
TI  - Haploidentical allogeneic hematopoietic stem cell transplantation in patients
      with high-risk soft tissue sarcomas: results of a single-center prospective
      trial.

PMID- 29367711
TI  - Chemotherapy with stem cell transplantation is more effective than immunotherapy
      in sporadic late onset nemaline myopathy with monoclonal gammopathy.

PMID- 29367712
TI  - Response to first-line treatment and histology are associated with achieving
      complete remission after the first salvage high-dose chemotherapy in relapsing
      germ cell tumor patients.
AB  - Sequential high-dose chemotherapy (HDCT) with autologous stem cell
      transplantation (ASCT) is a curative option in relapsing germ cell tumor (GCT)
      patients, and complete remission (CR) after the first ASCT (early CR2) is
      associated with favorable outcome. Prognostic factors predicting early CR2 have
      not been investigated so far. We analyzed consecutive patients with a first
      relapse of GCT treated with three sequential cycles of carboplatin/etoposide
      based HDCT with ASCT in the two largest academic centers in Switzerland. The
      cohort comprised 96 relapsing GCT patients, with 19 (19.8%) patients achieving
      early CR2 after the first HDCT cycle. The median progression-free survival and
      overall survival were not reached in patients achieving early CR2, whereas they
      were 9.6 months (P = 0.0301) and 34.8 months (P = 0.0684) for patients missing
      early CR2. Patients with early CR2 more often had CR1 after first-line bleomycin,
      etoposide, and cisplatin chemotherapy (68.4 vs. 31.6%; P = 0.0037) and an
      interval longer than 2 years between initial diagnosis and first HDCT (36.8 vs.
      15.6%; P = 0.0373), but less often a histology of mixed nonseminomatous tumor
      (46.8 vs. 21.1%; P = 0.0418). These data suggest that response to first-line
      chemotherapy, late relapse, and histology are associated with achieving early CR2
      after a first HDCT with ASCT in relapsing GCT patients.

PMID- 29367713
TI  - Secondary malignancies after high-dose chemotherapy in germ cell tumor patients:
      a 34-year retrospective study of the European Society for Blood and Marrow
      Transplantation (EBMT).
AB  - We aimed to assess the incidence and risk factors of secondary malignancy (SM) in
      the young adult patients who received high-dose chemotherapy (HDCT) for germ cell
      tumors (GCT). The EBMT database was interrogated. Criteria for patient selection
      included adult male GCT and HDCT administered in any line of therapy. Cumulative
      incidence methods were used to estimate the time-to-SM diagnosis. Univariable
      Fine and Gray proportional hazard regression evaluated risk factors of SM
      occurrence. From 1981 to 2015, 9153 autografts were identified. Among 5295
      patients, 59 cases of SM, developed after a median follow-up of 3.8 years, were
      registered. Of these patients, 23 (39%) developed hematologic SM, 34 (57.6%)
      solid SM (two patients had uncoded SM). Twenty-year cumulative incidence of solid
      versus hematologic SM was 4.17% (95% CI: 1.78-6.57) versus 1.37% (95% CI: 0.47
      2.27). Median overall survival after SM was significantly shorter for patients
      who developed hematologic SM versus solid SM (8.6 versus 34.4 months, p = 0.003).
      Age older than 40 years at the time of HDCT was significantly associated with
      hematologic, but not solid, SM development (p = 0.004 versus p = 0.234). SM
      occurrence post-HDCT showed different patterns of incidence and mortality in GCT.
      These data may be important to optimize patient selection, counseling and follow
      up after HDCT.

PMID- 29367714
TI  - Selected biological issues affecting relapse after stem cell transplantation:
      role of T-cell impairment, NK cells and intrinsic tumor resistance.
AB  - The graft vs. leukemia (GvL) effect as a method of preventing relapse is well
      described after allogeneic hematopoietic cell transplantation (HCT), but the
      mechanisms to this effect and how tumor sometimes develops resistance to GvL are
      just beginning to be understood. This article reviews and expands upon data
      presented at the Third International Workshop on Biology, Prevention and
      Treatment of Relapse after Stem Cell Transplantation held in Hamburg, Germany, in
      November 2016. We first discuss in detail the role that T-cell impairment early
      after HCT plays in relapse by looking at data from T cell-depleted approaches as
      well as the clear role that early T-cell recovery has shown in improving
      outcomes. We then review key findings regarding the role of specific KIR
      donor/recipient pairings that contribute to relapse prevention after HCT for
      several tumor types. Finally, we discuss a unique mouse model following the
      development of tumor resistance to GvL. Detailed molecular characterization of
      events marking the development of tumor resistance to the immunotherapy of GvL
      may help in developing future strategies to overcome immune escape.

PMID- 29367715
TI  - Biomarkers in chronic graft-versus-host disease: quo vadis?
AB  - Biomarkers are increasingly used for diagnosis and treatment of transplant
      related complications including the first biomarker-driven interventional trials
      of acute graft-versus-host disease (GvHD). In contrast, the development of
      biomarkers of chronic GvHD (cGvHD) has lagged behind due to a broader variety of
      manifestations, overlap with acute GvHD, a greater variation in time to onset and
      maximum severity, and lack of sufficient patient numbers within prospective
      trials. An international workshop organized by a North-American and European
      consortium was held in Marseille in March 2017 with the goal to discuss
      strategies for future biomarker development to guide cGvHD therapy. As a result
      of this meeting, two areas were prioritized: the development of prognostic
      biomarkers for subsequent onset of moderate/severe cGvHD, and in parallel, the
      development of qualified clinical-grade assays for biomarker quantification. The
      most promising prognostic serum biomarkers are CXCL9, ST2, matrix
      metalloproteinase-3, osteopontin, CXCL10, CXCL11, and CD163. Urine-proteomics and
      cellular subsets (CD4+ T-cell subsets, NK cell subsets, and CD19+CD21low B cells)
      represent additional potential prognostic biomarkers of cGvHD. A joint effort is
      required to verify the results of numerous exploratory trials before any of the
      potential candidates is ready for validation and subsequent clinical application.

PMID- 29367717
TI  - Sensitivity to lunar cycles prior to the 2007 eruption of Ruapehu volcano.
AB  - A long-standing question in Earth Science is the extent to which seismic and
      volcanic activity can be regulated by tidal stresses, a repeatable and
      predictable external excitation induced by the Moon-Sun gravitational force.
      Fortnightly tides, a ~14-day amplitude modulation of the daily tidal stresses
      that is associated to lunar cycles, have been suggested to affect volcano
      dynamics. However, previous studies found contradictory results and remain mostly
      inconclusive. Here we study how fortnightly tides have affected Ruapehu volcano
      (New Zealand) from 2004 to 2016 by analysing the rolling correlation between
      lunar cycles and seismic amplitude recorded close to the crater. The long-term
      (~1-year) correlation is found to increase significantly (up to confidence level
      of 5-sigma) during the ~3 months preceding the 2007 phreatic eruption of Ruapehu,
      thus revealing that the volcano is sensitive to fortnightly tides when it is
      prone to explode. We show through a mechanistic model that the real-time
      monitoring of seismic sensitivity to lunar cycles may help to detect the clogging
      of active volcanic vents, and thus to better forecast phreatic volcanic
      eruptions.

PMID- 29367716
TI  - Novel insights on new particle formation derived from a pan-european observing
      system.
AB  - The formation of new atmospheric particles involves an initial step forming
      stable clusters less than a nanometre in size (<~1 nm), followed by growth into
      quasi-stable aerosol particles a few nanometres (~1-10 nm) and larger (>~10 nm).
      Although at times, the same species can be responsible for both processes, it is
      thought that more generally each step comprises differing chemical contributors.
      Here, we present a novel analysis of measurements from a unique multi-station
      ground-based observing system which reveals new insights into continental-scale
      patterns associated with new particle formation. Statistical cluster analysis of
      this unique 2-year multi-station dataset comprising size distribution and
      chemical composition reveals that across Europe, there are different major
      seasonal trends depending on geographical location, concomitant with diversity in
      nucleating species while it seems that the growth phase is dominated by organic
      aerosol formation. The diversity and seasonality of these events requires an
      advanced observing system to elucidate the key processes and species driving
      particle formation, along with detecting continental scale changes in aerosol
      formation into the future.

PMID- 29367718
TI  - Enhanced Thermal Conductivity of Polyimide Composites with Boron Nitride
      Nanosheets.
AB  - A strategy was reported to prepare boron nitride nanosheets (BNNSs) by a molten
      hydroxide assisted liquid exfoliation from hexagonal boron nitride (h-BN) powder.
      BNNSs with an average thickness of 3 nm were obtained by a facile, low-cost, and
      scalable exfoliation method. Highly thermally conductive polyimide (PI) composite
      films with BNNSs filler were prepared by solution-casting process. The in-plane
      thermal conductivity of PI composite films with 7 wt% BNNSs is up to 2.95 W/mK,
      which increased by 1,080% compared to the neat PI. In contrast, the out-of plane
      thermal conductivity of the composites is 0.44 W/mK, with an increase by only
      76%. The high anisotropy of thermal conductivity was verified to be due to the
      high alignment of the BNNSs. The PI/BNNSs composite films are attractive for the
      thermal management applications in the field of next-generation electronic
      devices.

PMID- 29367720
TI  - Innate immune alterations are elicited in microglial cells before plaque
      deposition in the Alzheimer's disease mouse model 5xFAD.
AB  - Alzheimer's disease (AD) is the most common form of dementia characterized by the
      formation of amyloid plaques (Abeta). Over the last decade, the important role of
      the innate immune system for the disease development has been established.
      Chronic activation of microglial cells creates a proinflammatory environment,
      which is believed to be central for the development of the disease as well as its
      progression. We used the AD mouse model 5xFAD to investigate if inflammatory
      alterations are present in microglial cells before plaque deposition. We applied
      mass spectrometry and bioinformation analysis to elucidate early microglial
      alterations. Interestingly, we found the cytokines IL1beta and IL10 to be
      elevated in the 5xFAD brain after the formation of Abeta plaque at 10 weeks only.
      Using mass spectrometry analysis of microglial cells with bioinformation
      analysis, we found JAK/STAT, p38 MAPK and Interleukin pathways affected in
      microglial cells before plaque deposition at 6 weeks. At 10 weeks, GO analysis
      showed affected pathways related to interferon-gamma regulation and MAPK
      pathways. Our study points toward early inflammatory changes in microglial cells
      even before the accumulation of Abeta.

PMID- 29367719
TI  - The cytomegalovirus protein US31 induces inflammation through mono-macrophages in
      systemic lupus erythematosus by promoting NF-kappaB2 activation.
AB  - It has been hypothesized that human cytomegalovirus (HCMV) infection, especially
      in monocyte and CD34 (+) myeloid cells, acts as a important regulator of immune
      system to promote inflammation in multiple autoimmune diseases. The aim of this
      study was to elucidate the HCMV gene expression profiles in the peripheral blood
      mononuclear cells (PBMCs) of SLE patients and demonstrate the effect and
      mechanism of viral gene associated with SLE in mono-macrophages functions. Using
      two RNA-Seq techniques in combination with RT-PCR, 11 viral genes mainly
      associated with latent HCMV infection were identified in the PBMCs of SLE
      patients. Among these viral genes, US31 with previously unknown function was
      highly expressed in the PBMCs of SLE patients compared to healthy controls.
      Analysis of function indicated that US31 expression could induce inflammation in
      monocyte and macrophage and stimulate macrophage differentiation toward an M1
      macrophage phenotype. Screening via protein chips in combination with
      bioinformatic analysis and consequent detection of mono-macrophages function
      indicates that the direct interaction between US31 and NF-kappaB2 contributed the
      NF-kB2 activation. Consequent analysis indicated US31 directly interacted with NF
      kappaB2, contribute to the polyubiquitination of the phosphorylated p100 and
      consequent activation of NF-kappaB2. Taken together, our data uncovered a
      previously unknown role of the HCMV protein US31 in inducing NF-kappaB-mediated
      mono-macrophage inflammation in the pathogenesis and development of SLE. Our
      findings provide a foundation for the continued investigation of novel
      therapeutic targets for SLE patients.

PMID- 29367721
TI  - Simultaneous realization of slow and fast acoustic waves using a fractal
      structure of Koch curve.
AB  - An acoustic metamaterial based on a fractal structure, the Koch curve, is
      designed to simultaneously realize slow and fast acoustic waves. Owing to the
      multiple transmitting paths in the structure resembling the Koch curve, the
      acoustic waves travelling along different paths interfere with each other.
      Therefore, slow waves are created on the basis of the resonance of a Koch-curve
      shaped loop, and meanwhile, fast waves even with negative group velocities are
      obtained due to the destructive interference of two acoustic waves with opposite
      phases. Thus, the transmission of acoustic wave can be freely manipulated with
      the Koch-curve shaped structure.

PMID- 29367722
TI  - Slow moving neural source in the epileptic hippocampus can mimic progression of
      human seizures.
AB  - Fast and slow neural waves have been observed to propagate in the human brain
      during seizures. Yet the nature of these waves is difficult to study in a
      surgical setting. Here, we report an observation of two different traveling waves
      propagating in the in-vitro epileptic hippocampus at speeds similar to those in
      the human brain. A fast traveling spike and a slow moving wave were recorded
      simultaneously with a genetically encoded voltage sensitive fluorescent protein
      (VSFP Butterfly 1.2) and a high speed camera. The results of this study indicate
      that the fast traveling spike is NMDA-sensitive but the slow moving wave is not.
      Image analysis and model simulation demonstrate that the slow moving wave is
      moving slowly, generating the fast traveling spike and is, therefore, a moving
      source of the epileptiform activity. This slow moving wave is associated with a
      propagating neural calcium wave detected with calcium dye (OGB-1) but is
      independent of NMDA receptors, not related to ATP release, and much faster than
      those previously recorded potassium waves. Computer modeling suggests that the
      slow moving wave can propagate by the ephaptic effect like epileptiform activity.
      These findings provide an alternative explanation for slow propagation seizure
      wavefronts associated with fast propagating spikes.

PMID- 29367723
TI  - Double-layered protein nanoparticles induce broad protection against divergent
      influenza A viruses.
AB  - Current influenza vaccines provide limited protection against circulating
      influenza A viruses. A universal influenza vaccine will eliminate the intrinsic
      limitations of the seasonal flu vaccines. Here we report methodology to generate
      double-layered protein nanoparticles as a universal influenza vaccine. Layered
      nanoparticles are fabricated by desolvating tetrameric M2e into protein
      nanoparticle cores and coating these cores by crosslinking headless HAs.
      Representative headless HAs of two HA phylogenetic groups are constructed and
      purified. Vaccinations with the resulting protein nanoparticles in mice induces
      robust long-lasting immunity, fully protecting the mice against challenges by
      divergent influenza A viruses of the same group or both groups. The results
      demonstrate the importance of incorporating both structure-stabilized HA stalk
      domains and M2e into a universal influenza vaccine to improve its protective
      potency and breadth. These potent disassemblable protein nanoparticles indicate a
      wide application in protein drug delivery and controlled release.

PMID- 29367724
TI  - Elimination of stem-like cancer cell side-population by auranofin through
      modulation of ROS and glycolysis.
AB  - Cancer side-population (SP) represents a sub-population of stem-like cancer cells
      that have an important role in drug resistance due to their high expression of
      the ATP-binding cassette transporter ABCG2 involved in drug export. Auranofin
      (AF), a clinical drug of gold complex that is used in treatment of rheumatoid
      arthritis, has been reported inducing tumor antiproliferation. However, whether
      AF can impact SP cells remains unclear. Our study showed that AF caused a
      depletion of SP cells and a downregulation of stem cell markers, and impaired
      their ability to form tumor colonies in vitro and incidence to develop tumors in
      vivo of lung cancer cells. Reactive oxygen species (ROS) had an important role in
      mediating AF-induced depletion of SP cells, which could be reversed by
      antioxidant NAC. Further study revealed that AF could also cause ATP depletion by
      inhibition of glycolysis. The depletion of cellular ATP might impair the function
      of ABCG2 pump, leading to increased drug accumulation within the cells and thus
      enhancing anticancer activity of chemotherapeutic agents such as adriamycin.
      Synergistic effect of AF and adriamycin was demonstrated both in vitro and in
      vivo. Simultaneous increase of ROS and inhibition of glycolysis is a novel
      strategy to eliminate stem-like cancer cells. Combination of AF with adriamycin
      seems to be promising to enhance therapeutic effectiveness.

PMID- 29367725
TI  - Omentectomy Prevents Metabolic Syndrome By Reducing Appetite and Body Weight In A
      Diet-Induced Obesity Rat Model.
AB  - Visceral fat deposition is associated with impairment of glucose and lipid
      metabolism while leptin levels are frequently related to subcutaneous fat area.
      At present, there is considerable controversy regarding the role of visceral
      adipose tissue accumulation in the development of metabolic syndrome (MS). Here
      we show the effects of omentectomy on the liver and MS in a diet induced obesity
      rat model. Our results reveal that undergoing omentectomy previously the
      establishment of the diet-induced-obesity reduced significantly body weight gain
      and avoid the development of MS, including non-alcoholic fatty liver disease.
      Intriguingly, the significantly lower body weight gain was due to decreased food
      intake. Omentum drives obesity progression through leptin resistance mediated by
      C-reactive protein, Interleucin (IL)-6 and high lipolysis activity. Omentum
      removal reversed immediately the increased plasma levels of CRP and IL-6 and
      gradually food intake, weight gain, and features of MS in diet-induced-obesity.
      Omentectomy caused no changes in normal-weigh-rats. This report displays causal
      mechanism by which omentum promotes obesity and propose omentectomy as a
      promising procedure in MS prevention.

PMID- 29367726
TI  - Genome editing for dissecting and curing human genetic diseases.

PMID- 29367727
TI  - Verification of Argentine ant defensive compounds and their behavioral effects on
      heterospecific competitors and conspecific nestmates.
AB  - The invasive Argentine ant (Linepithema humile) has become established worldwide
      in regions with Mediterranean or subtropical climates. The species typically
      disrupts the balance of natural ecosystems by competitively displacing some
      native ant species via strong exploitation and interference competition. Here we
      report that Argentine ants utilize glandular secretions for inter and intra
      specific communications during aggressive interactions with a heterospecific
      competitor, California harvester ant (Pogonomyrmex californicus). Chemical
      analyses indicated that Argentine ants deploy glandular secretions containing two
      major volatile iridoids, dolichodial and iridomyrmecin, on the competitor's
      cuticular surface during aggressive interactions. Bioassays indicated that the
      glandular secretions function as a defensive allomone, causing high levels of
      irritation in the heterospecific. Furthermore, the same glandular secretions
      elicited alarm and attraction of conspecific nestmates, potentially enabling more
      rapid/coordinated defense by the Argentine ants. Two major volatile constituents
      of the glandular secretion, dolichodial and iridomyrmecin, were sufficient to
      elicit these responses in conspecifics (as a mixture or individual compounds).
      The current study suggests that invasive Argentine ants' superior exploitation
      and interference competition may rely on the species' effective semiochemical
      parsimony.

PMID- 29367728
TI  - Combined analysis of the salivary microbiome and host defence peptides predicts
      dental disease.
AB  - Understanding the triad of host response, microbiome and disease status is
      potentially informative for disease prediction, prevention, early intervention
      and treatment. Using longitudinal assessment of saliva and disease status, we
      demonstrated that partial least squares modelling of microbial, immunological and
      clinical measures, grouped children according to future dental disease status.
      Saliva was collected and dental health assessed in 33 children aged 4 years, and
      again 1-year later. The composition of the salivary microbiome was assessed and
      host defence peptides in saliva were quantified. Principal component analysis of
      the salivary microbiome indicated that children clustered by age and not disease
      status. Similarly, changes in salivary host defence peptides occurred with age
      and not in response to, or preceding dental caries. Partial least squares
      modelling of microbial, immunological and clinical baseline measures clustered
      children according to future dental disease status. These data demonstrate that
      isolated evaluation of the salivary microbiome or host response failed to predict
      dental disease. In contrast, combined assessment of both host response together
      with the microbiome revealed clusters of health and disease. This type of
      approach is potentially relevant to myriad diseases that are modified by host
      microbiome interactions.

PMID- 29367729
TI  - Ethanolic extract of the fungus Trichoderma stromaticum decreases inflammation
      and ameliorates experimental cerebral malaria in C57BL/6 mice.
AB  - Increased resistance to the first-line treatment against P. falciparum malaria,
      artemisinin-based combination therapies, has been reported. Here, we tested the
      effect of crude ethanolic extract of the fungus Trichoderma stromaticum (Ext-Ts)
      on the growth of P. falciparum NF54 in infected human red blood cells (ihRBCs)
      and its anti-malarial and anti-inflammatory properties in a mouse model of
      experimental cerebral malaria. For this purpose, ihRBCs were treated with Ext-Ts
      and analysed for parasitaemia; C57BL/6 mice were infected with P. berghei ANKA
      (PbA), treated daily with Ext-Ts, and clinical, biochemical, histological and
      immunological features of the disease were monitored. It was observed that Ext-Ts
      presented a dose-dependent ability to control P. falciparum in ihRBCs. In
      addition, it was demonstrated that Ext-Ts treatment of PbA-infected mice was able
      to increase survival, prevent neurological signs and decrease parasitaemia at the
      beginning of infection. These effects were associated with systemically decreased
      levels of lipids and IFN-gamma, ICAM-1, VCAM-1 and CCR5 cerebral expression,
      preserving blood brain barrier integrity and attenuating the inflammatory lesions
      in the brain, liver and lungs. These results suggest that Ext-Ts could be a
      source of immunomodulatory and antimalarial compounds that could improve the
      treatment of cerebral malaria.

PMID- 29367730
TI  - Effects of temperature and photosynthetically active radiation on virioplankton
      decay in the western Pacific Ocean.
AB  - In this study, we investigated virioplankton decay rates and their responses to
      changes in temperature and photosynthetically active radiation (PAR) in the
      western Pacific Ocean. The mean decay rates for total, high-fluorescence, and low
      fluorescence viruses were 1.64 +/- 0.21, 2.46 +/- 0.43, and 1.57 +/- 0.26% h-1,
      respectively. Higher temperatures and PAR increased viral decay rates, and the
      increases in the decay rates of low-fluorescence viruses were greater than those
      of high-fluorescence viruses. Our results revealed that low-fluorescence viruses
      are more sensitive to warming and increasing PAR than are high-fluorescence
      viruses, which may be related to differences in their biological characteristics,
      such as the density of packaged nucleic acid materials. Our study provided
      experimental evidence for the responses of natural viral communities to changes
      in global environmental factors (e.g., temperature and solar radiation).

PMID- 29367731
TI  - Vitamin D status in irritable bowel syndrome and the impact of supplementation on
      symptoms: what do we know and what do we need to know?
AB  - BACKGROUND: Low vitamin D status is associated with risk of colorectal cancer and
      has been implicated in inflammatory bowel disease. Irritable bowel syndrome (IBS)
      is a chronic, relapsing, functional bowel disorder. A nascent literature suggests
      a role for vitamin D in IBS, but this has not been collated or critiqued. To
      date, seven studies have been published: four observational studies and three
      randomised controlled trials (RCTs). All observational studies reported that a
      substantial proportion of the IBS population was vitamin D deficient. Two
      intervention studies reported improvement in IBS symptom severity scores and
      quality of life (QoL) with vitamin D supplementation. There are limited data
      around the role of vitamin D in IBS. CONCLUSIONS: The available evidence suggests
      that low vitamin D status is common among the IBS population and merits
      assessment and rectification for general health reasons alone. An inverse
      correlation between serum vitamin D and IBS symptom severity is suggested and
      vitamin D interventions may benefit symptoms. However, the available RCTs do not
      provide strong, generalisable evidence; larger and adequately powered
      interventions are needed to establish a case for therapeutic application of
      vitamin D in IBS.

PMID- 29367732
TI  - Associations between 25-hydroxyvitamin D levels, body composition and metabolic
      profiles in young women.
AB  - BACKGROUND/OBJECTIVES: Cardiovascular disease (CVD) is a major cause of mortality
      and morbidity globally. Results from previous studies are inconsistent and it
      remains unclear whether low-serum 25 OHD levels are associated with an increased
      risk of CVD. These associations have been little studied in young women. The aim
      of this study was to assess the relationship between serum 25 OHD and obesity,
      body composition, metabolic profiles and blood pressure in young women.
      SUBJECTS/METHODS: Women aged 16-25 years living in Victoria, Australia, were
      recruited through Facebook advertising in this cross-sectional study.
      Participants completed an online survey and attended a site visit in a fasted
      state, where parameters, including blood pressure, anthropometry, metabolic
      profiles, serum 25 OHD levels and body composition (using dual energy X-ray
      absorptiometry) were measured. RESULTS: A total of 557 participants were
      recruited into this study. Multiple linear regression analysis showed that after
      adjusting for visceral fat, season, smoking, physical activity, age, alcohol
      intake, oral contraceptive use, country of birth, taking multivitamins and taking
      vitamin D supplement, a 10 nmol/L increase in 25 OHD levels was associated with
      0.65% greater HDL levels (p = 0.016) and 0.92% greater triglyceride levels (p =
      0.003). It was also associated with 0.48% lower BMI (p < 0.001), 0.50% lower
      total fat percentage (p < 0.001), 0.09% lower visceral fat percentage (p <
      0.001), 0.14% lower visceral fat to total fat ratio (p < 0.001) and 0.36% lower
      trunk fat to total fat ratio (p < 0.001), after adjustment for season, smoking,
      physical activity, age, alcohol intake, oral contraceptive use, country of birth,
      taking multivitamins and taking vitamin D supplements. Although these
      associations were statistically significant, they were very small in magnitude
      and of uncertain clinical significance. CONCLUSIONS: These findings may help to
      explain an association between 25 OHD levels and CVD risk factors through
      associations with HDL, BMI, total body and visceral fat mass. Possible underlying
      mechanisms warrant further investigation.

PMID- 29367733
TI  - Skipping breakfast is associated with lower diet quality in young US children.
AB  - BACKGROUND/OBJECTIVES: Breakfast consumption has been shown to impact children's
      growth and development, but the influence of breakfast skipping on total daily
      intakes is not known. The purpose of this study was to examine the differences in
      nutritional intakes and food consumption between children who consume breakfast
      versus those who do not. SUBJECTS/METHODS: Dietary recall data were assessed for
      2-year-old to 5-year-old children (n = 3443) and 6-year-old to 12-year-old
      children (n = 5147) from NHANES 2005-2012. Dietary intakes and diet quality
      scores were compared across breakfast consumption and skipping with means and 95%
      confidence interval. RESULTS: Children who skipped breakfast on the day of intake
      had significantly lower energy intakes for the total day (5911 vs 6723 kJ) but
      had greater energy intakes from non-breakfast meals and snacks. Children who
      skipped breakfast consumed nearly 40% of the day's intake (2332 kJ of 5911 kJ)
      from snacks, with 586 kJ from snacks as added sugars. Breakfast skipping was also
      related to significantly lower intakes of fiber, folate, iron, and calcium
      intakes. Overall diet quality scores, as well as fruit, whole fruit, whole
      grains, dairy and empty calorie subscale scores were significantly better in
      children who ate breakfast. CONCLUSIONS: Children who skipped breakfast presented
      poorer overall diet quality and lower total intakes commonly obtained at
      breakfast. To address missed opportunities, nutrition professionals should
      encourage children's consumption of a nutritious breakfast to support overall
      diet quality.

PMID- 29367734
TI  - Variants of the 5'-terminal region of p53 mRNA influence the ribosomal scanning
      and translation efficiency.
AB  - The p53 protein is one of the major cell cycle regulators. The protein is
      expressed as at least twelve protein isoforms resulting from the use of
      alternative promoters, alternative splicing or downstream initiation codons.
      Importantly, there is growing evidence that translation initiation of p53 mRNA
      may be regulated by the structure and length of the naturally occurring variants
      of the 5'-terminal region of p53 mRNA transcripts. Here, several mRNA constructs
      were synthesized with variable length of the p53 5'-terminal regions and encoding
      luciferase reporter protein, and their translation was monitored continuously in
      situ in a rabbit reticulocyte lysate system. Moreover, four additional mRNA
      constructs were prepared. In two constructs, the structural context of AUG1
      initiation codon was altered while in the other two constructs, characteristic
      hairpin motifs present in the p53 5'-terminal region were changed. Translation of
      the last two constructs was also performed in the presence of the cap analogue to
      test the function of the 5'-terminal region in cap-independent translation
      initiation. Superposition of several structural factors connected with the length
      of the 5'-terminal region, stable elements of the secondary structure, structural
      environment of the initiation codon and IRES elements greatly influenced the
      ribosomal scanning and translation efficiency.

PMID- 29367735
TI  - A genome-wide association study in the Japanese population identifies the 12q24
      locus for habitual coffee consumption: The J-MICC Study.
AB  - Coffee is one of the most widely consumed beverages worldwide, and its role in
      human health has received much attention. Although genome-wide association
      studies (GWASs) have investigated genetic variants associated with coffee
      consumption in European populations, no such study has yet been conducted in an
      Asian population. Here, we conducted a GWAS to identify common genetic variations
      that affected coffee consumption in a Japanese population of 11,261 participants
      recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J
      MICC) study. Coffee consumption was collected using a self-administered
      questionnaire, and converted from categories to cups/day. In the discovery stage
      (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met
      suggestive significance (P < 1 * 10-6). In the replication stage (n = 4,949), the
      lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated
      with habitual coffee consumption (P = 2.2 * 10-6), whereas the lead variant for
      the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery
      and replication populations, and the combined analysis using all subjects,
      revealed that rs2074356 achieved genome-wide significance (P = 2.2 * 10-16 for a
      meta-analysis). These findings indicate that the 12q24.12-13 locus is associated
      with coffee consumption among a Japanese population.

PMID- 29367736
TI  - Statins do not increase Markers of Cerebral Angiopathies in patients with
      Cardioembolic Stroke.
AB  - We investigated whether pre-treatment with statins is associated with surrogate
      markers of amyloid and hypertensive angiopathies in patients who need to start
      long-term oral anticoagulation therapy. A prospective multicenter study of
      patients naive for oral anticoagulants, who had an acute cardioembolic stroke.
      MRI was performed at admission to evaluate microbleeds, leukoaraiosis and
      superficial siderosis. We collected data on the specific statin compound, the
      dose and the statin intensity. We performed bivariate analyses and a logistic
      regression to investigate variables associated with microbleeds. We studied 470
      patients (age 77.5 +/- 6.4 years, 43.7% were men), and 193 (41.1%) of them
      received prior treatment with a statin. Microbleeds were detected in 140 (29.8%),
      leukoaraiosis in 388 (82.5%) and superficial siderosis in 20 (4.3%) patients. The
      presence of microbleeds, leukoaraiosis or superficial siderosis was not related
      to pre-treatment with statins. Microbleeds were more frequent in patients with
      prior intracerebral hemorrhage (OR 9.7, 95% CI 1.06-90.9) and in those pre
      treated antiplatelets (OR 1.66, 95% CI 1.09-2.53). Prior treatment with statins
      was not associated with markers of bleeding-prone cerebral angiopathies in
      patients with cardioembolic stroke. Therefore, previous statin treatment should
      not influence the decision to initiate or withhold oral anticoagulation if these
      neuroimaging markers are detected.

PMID- 29367737
TI  - miR-375 is involved in Hippo pathway by targeting YAP1/TEAD4-CTGF axis in gastric
      carcinogenesis.
AB  - miR-375 is a tumor-suppressive microRNA (miRNA) in gastric cancer (GC). However,
      its molecular mechanism remains unclear. The aim of this study is to
      comprehensively investigate how miR-375 is involved in Hippo pathway by targeting
      multiple oncogenes. miR-375 expression in gastric cancer cell lines and primary
      GC was investigated by qRT-PCR. The regulation of YAP1, TEAD4, and CTGF
      expression by miR-375 was evaluated by qRT-PCR, western blot, and luciferase
      reporter assays, respectively. The functional roles of the related genes were
      examined by siRNA-mediated knockdown or ectopic expression assays. The clinical
      significance and expression correlation analysis of miR-375, YAP1, and CTGF were
      performed in primary GCs. TCGA cohort was also used to analyze the expression
      correlation of YAP1, TEAD4, CTGF, and miR-375 in primary GCs. miR-375 was down
      regulated in GC due to promoter methylation and histone deacetylation. miR-375
      downregulation was associated with unfavorable outcome and lymph node metastasis.
      Ectopic expression of miR-375 inhibited tumor growth in vitro and in vivo. Three
      components of Hippo pathway, YAP1, TEAD4 and CTGF, were revealed to be direct
      targets of miR-375. The expression of three genes showed a negative correlation
      with miR-375 expression and YAP1 re-expression partly abolished the tumor
      suppressive effect of miR-375. Furthermore, CTGF was confirmed to be the key
      downstream of Hippo-YAP1 cascade and its knockdown phenocopied siYAP1 or miR-375
      overexpression. YAP1 nuclear accumulation was positively correlated with CTGF
      cytoplasmic expression in primary GC tissues. Verteporfin exerted an anti
      oncogenic effect in GC cell lines by quenching CTGF expression through YAP1
      degradation. In short, miR-375 was involved in the Hippo pathway by targeting
      YAP1-TEAD4-CTGF axis and enriched our knowledge on the miRNA dysregulation in
      gastric tumorigenesis.

PMID- 29367738
TI  - Differential effects of reticulophagy and mitophagy on nonalcoholic fatty liver
      disease.
AB  - Autophagy affects the pathological progression of non-alcoholic fatty liver
      disease (NAFLD); however, the precise role of autophagy in NAFLD remains unclear.
      In this study, we want to identify the role of autophagy including reticulophagy
      and mitophagy in NAFLD pathogenesis. When HepG2 cells were treated with 400 MUM
      oleic acid (OA), increased reticulophagy was induced 8 h after treatment, which
      correlated with an anti-apoptotic response as shown by the activation of the
      PI3K/AKT pathway, an increase in BCL-2 expression, and the downregulation of OA
      induced lipotoxicity. When treated with OA for 24 h, DRAM expression-dependent
      mitophagy resulted in increased apoptosis in HepG2 cells. Inhibition of
      reticulophagy aggravated and increased lipotoxicity-induced apoptosis 8 h after
      treatment; however, the inhibition of mitophagy decreased hepatocyte apoptosis
      after 24 h of OA treatment. Results from the analysis of patient liver samples
      showed that autophagic flux increased in patients with mild or severe NAFL.
      PI3K/AKT phosphorylation was observed only in samples from patients with low
      grade steatosis, whereas DRAM expression was increased in samples from patients
      with high-grade steatosis. Together, our results demonstrate that reticulophagy
      and mitophagy are independent, sequential events that influence NAFLD
      progression, which opens new avenues for investigating new therapeutics in NAFLD.

PMID- 29367739
TI  - Mixed pyruvate labeling enables backbone resonance assignment of large proteins
      using a single experiment.
AB  - Backbone resonance assignment is a critical first step in the investigation of
      proteins by NMR. This is traditionally achieved with a standard set of
      experiments, most of which are not optimal for large proteins. Of these, HNCA is
      the most sensitive experiment that provides sequential correlations. However,
      this experiment suffers from chemical shift degeneracy problems during the
      assignment procedure. We present a strategy that increases the effective
      resolution of HNCA and enables near-complete resonance assignment using this
      single HNCA experiment. We utilize a combination of 2-13C and 3-13C pyruvate as
      the carbon source for isotope labeling, which suppresses the one bond
      (1Jalphabeta) coupling providing enhanced resolution for the Calpha resonance and
      amino acid-specific peak shapes that arise from the residual coupling. Using this
      approach, we can obtain near-complete (>85%) backbone resonance assignment of a
      42 kDa protein using a single HNCA experiment.

PMID- 29367741
TI  - Population genetic structure of Diaphorina citri Kuwayama (Hemiptera: Liviidae):
      host-driven genetic differentiation in China.
AB  - The Asian citrus psyllid Diaphorina citri Kuwayama is a major pest in citrus
      production, transmitting Candidatus Liberibacter asiaticus. It has spread widely
      across eastern and southern China. Unfortunately, little is known about the
      genetic diversity and population structure of D. citri, making pest control
      difficult. In this study, nine specifically developed SSR markers and three known
      mitochondrial DNA were used for population genetics study of D. citri using 225
      samples collected from all 7 distribution regions in China. Based on the SSR
      data, D. citri was found highly diverse with a mean observed heterozygosity of
      0.50, and three subgroups were structured by host plant: (i) Shatangju, NF
      mandarin and Ponkan; (ii) Murraya paniculata and Lemon; (iii) Citrus unshiu,
      Bingtangcheng, Summer orange and Navel. No significant genetic differences were
      found with mtDNA data. We suggested the host-associated divergence is likely to
      have occurred very recently. A unimodal distribution of paired differences, the
      negative and significant Tajima's D and Fu's F S parameters among mtDNA suggested
      a recent demographic expansion. The extensive citrus cultivation and increased
      suitable living habitat was recommended as a key for this expansion event.

PMID- 29367740
TI  - Combined chemical genetics and data-driven bioinformatics approach identifies
      receptor tyrosine kinase inhibitors as host-directed antimicrobials.
AB  - Antibiotic resistance poses rapidly increasing global problems in combatting
      multidrug-resistant (MDR) infectious diseases like MDR tuberculosis, prompting
      for novel approaches including host-directed therapies (HDT). Intracellular
      pathogens like Salmonellae and Mycobacterium tuberculosis (Mtb) exploit host
      pathways to survive. Only very few HDT compounds targeting host pathways are
      currently known. In a library of pharmacologically active compounds (LOPAC)-based
      drug-repurposing screen, we identify multiple compounds, which target receptor
      tyrosine kinases (RTKs) and inhibit intracellular Mtb and Salmonellae more
      potently than currently known HDT compounds. By developing a data-driven in
      silico model based on confirmed targets from public databases, we successfully
      predict additional efficacious HDT compounds. These compounds target host RTK
      signaling and inhibit intracellular (MDR) Mtb. A complementary human kinome siRNA
      screen independently confirms the role of RTK signaling and kinases (BLK, ABL1,
      and NTRK1) in host control of Mtb. These approaches validate RTK signaling as a
      drugable host pathway for HDT against intracellular bacteria.

PMID- 29367742
TI  - Young and healthy C57BL/6 J mice performing sprint interval training reveal
      gender- and site-specific changes to the cortical bone.
AB  - Physical exercise is considered to impede the bone loss associated with
      physiological ageing however, a training program that efficiently leads to bone
      accrual in the healthy does not yet exist. We turned to the C57BL/6 J mouse and
      designed a sprint interval training for treadmill that was tailored to the
      individual performance limits. It consisted of four weeks with five training
      sessions each, followed by another four weeks with three. After completion of the
      training period, mice were sacrificed and the hind legs were analyzed via uCT and
      MRI for changes in bone parameters and muscle volume, respectively. Increased
      performance limits in both sexes confirmed an effect of the treadmill training.
      However, while male tibiae after eight weeks revealed a significant reduction of
      cortical bone mass at the distal metaphysis, the cross sectional analysis of
      female tibiae showed a transient decrease of cortical bone mass after four weeks
      that was reversed into a significant accrual after eight weeks of training and
      occurred over the entire length of the tibia. The observed net reduction of
      female bone mass after four weeks of training is suggestive of a remodelling
      process which may be delayed in the males.

PMID- 29367743
TI  - Vaccine vectors based on Adenovirus 19a/64 exhibit broad cellular tropism and
      potently restimulate HCMV-specific T cell responses ex vivo.
AB  - Human Cytomegalovirus (HCMV) remains a major health burden and the development of
      a vaccine is a global priority. We developed new viral vectors delivering the T
      cell immunogens IE-1 and pp65 based on Adenovirus 19a/64 (Ad19a/64), a member of
      subgroup D. In this ex vivo study, the novel vectors were compared side by side
      to Ad5 or modified Vaccinia Ankara (MVA) strains expressing the same transgenes.
      We found that unlike Ad5, Ad19a/64 vectors readily transduce a broad panel of
      immune cells, including monocytes, T cells, NK cells and monocyte-derived
      dendritic cells (moDCs). Both Ad19a/64- and MVA-transduced moDCs efficiently
      restimulated IE-1 or pp65-specific T cells but MVA induced a higher amount of
      cytotoxicity in this cell type. Ad5 and Ad19 induced upregulation of CD86 and HLA
      DR in moDCs whereas expression of CD80 and CD83 was largely unaltered. By
      contrast, MVA transduction led to downregulation of all markers. Taken together,
      our data demonstrate that Ad19a/64 is a promising vector for the delivery of HCMV
      immunogens since it transduces dendritic cells with an efficiency that is
      comparable to MVA, but cytotoxicity and interference with dendritic cell
      maturation are less pronounced.

PMID- 29367744
TI  - Overexpression of parkin protects retinal ganglion cells in experimental
      glaucoma.
AB  - Glaucoma is a leading cause of irreversible blindness and characterized by
      progressive damage of retinal ganglion cells (RGCs). Growing evidences have
      linked impaired mitophagy with neurodegenerative diseases, while the E3 ubiquitin
      ligase parkin may play a key role. However, the pathophysiological relationship
      between parkin and glaucoma remains largely unknown. Using chronic hypertensive
      glaucoma rats induced by translimbal laser photocoagulation, we show here that
      the protein level of parkin and its downstream optineurin proteins were increased
      in hypertensive retinas. The ratio of LC3-II to LC3-I, the number of
      mitophagosomes, and unhealthy mitochondria were increased in hypertensive optic
      nerves. Overexpression of parkin by viral vectors increased RGC survival in
      glaucomatous rats in vivo and under excitotoxicity in vitro. It also promoted
      optineurin expression and improved mitochondrial health. In parkin-overexpressed
      glaucomatous rats, the ratio of LC3-II to LC3-I, LAMP1 level, and the number of
      mitophagosomes in optic nerve were decreased at 3 days, yet increased at 2 weeks
      following intraocular pressure (IOP) elevation. These findings demonstrate that
      dysfunction of mitophagy exist in RGCs of glaucomatous rats. Overexpression of
      parkin exerted a significant protective effect on RGCs and partially restored
      dysfunction of mitophagy in response to cumulative IOP elevation.

PMID- 29367745
TI  - A systematic analysis of nucleosome core particle and nucleosome-nucleosome
      stacking structure.
AB  - Chromatin condensation is driven by the energetically favourable interaction
      between nucleosome core particles (NCPs). The close NCP-NCP contact, stacking, is
      a primary structural element of all condensed states of chromatin in vitro and in
      vivo. However, the molecular structure of stacked nucleosomes as well as the
      nature of the interactions involved in its formation have not yet been
      systematically studied. Here we undertake an investigation of both the structural
      and physico-chemical features of NCP structure and the NCP-NCP stacking. We
      introduce an "NCP-centred" set of parameters (NCP-NCP distance, shift, rise,
      tilt, and others) that allows numerical characterisation of the mutual positions
      of the NCPs in the stacking and in any other structures formed by the NCP. NCP
      stacking in more than 140 published NCP crystal structures were analysed. In
      addition, coarse grained (CG) MD simulations modelling NCP condensation was
      carried out. The CG model takes into account details of the nucleosome structure
      and adequately describes the long range electrostatic forces as well as excluded
      volume effects acting in chromatin. The CG simulations showed good agreement with
      experimental data and revealed the importance of the H2A and H4 N-terminal tail
      bridging and screening as well as tail-tail correlations in the stacked
      nucleosomes.

PMID- 29367746
TI  - Contrasting maternal and paternal genetic variation of hunter-gatherer groups in
      Thailand.
AB  - The Maniq and Mlabri are the only recorded nomadic hunter-gatherer groups in
      Thailand. Here, we sequenced complete mitochondrial (mt) DNA genomes and ~2.364
      Mbp of non-recombining Y chromosome (NRY) to learn more about the origins of
      these two enigmatic populations. Both groups exhibited low genetic diversity
      compared to other Thai populations, and contrasting patterns of mtDNA and NRY
      diversity: there was greater mtDNA diversity in the Maniq than in the Mlabri,
      while the converse was true for the NRY. We found basal uniparental lineages in
      the Maniq, namely mtDNA haplogroups M21a, R21 and M17a, and NRY haplogroup K.
      Overall, the Maniq are genetically similar to other negrito groups in Southeast
      Asia. By contrast, the Mlabri haplogroups (B5a1b1 for mtDNA and O1b1a1a1b and
      O1b1a1a1b1a1 for the NRY) are common lineages in Southeast Asian non-negrito
      groups, and overall the Mlabri are genetically similar to their linguistic
      relatives (Htin and Khmu) and other groups from northeastern Thailand. In
      agreement with previous studies of the Mlabri, our results indicate that the
      Malbri do not directly descend from the indigenous negritos. Instead, they likely
      have a recent origin (within the past 1,000 years) by an extreme founder event
      (involving just one maternal and two paternal lineages) from an agricultural
      group, most likely the Htin or a closely-related group.

PMID- 29367747
TI  - Ultrafast quantum beats of anisotropic excitons in atomically thin ReS2.
AB  - Quantum beats, periodic oscillations arising from coherent superposition states,
      have enabled exploration of novel coherent phenomena. Originating from strong
      Coulomb interactions and reduced dielectric screening, two-dimensional transition
      metal dichalcogenides exhibit strongly bound excitons either in a single
      structure or hetero-counterpart; however, quantum coherence between excitons is
      barely known to date. Here we observe exciton quantum beats in atomically thin
      ReS2 and further modulate the intensity of the quantum beats signal.
      Surprisingly, linearly polarized excitons behave like a coherently coupled three
      level system exhibiting quantum beats, even though they exhibit anisotropic
      exciton orientations and optical selection rules. Theoretical studies are also
      provided to clarify that the observed quantum beats originate from pure quantum
      coherence, not from classical interference. Furthermore, we modulate on/off
      quantum beats only by laser polarization. This work provides an ideal laboratory
      toward polarization-controlled exciton quantum beats in two-dimensional
      materials.

PMID- 29367748
TI  - Transport of Photonic Bloch Wave in Arrayed Two-Level Atoms.
AB  - In a quantum system of arrayed two-level atoms interacting with light, the
      interacted (dressed) photon is propagating in a periodic medium and its
      eigenstate ought to be of Bloch type with lattice symmetry. As the energy of
      photon is around the spacing between the two atomic energy levels, the photon
      will be absorbed and is not in the propagating mode but the attenuated mode.
      Therefore an energy gap exists in the dispersion relation of the photonic Bloch
      wave of dressed photon in addition to the nonlinear behaviors due to atom-light
      interactions. There follows several interesting results which are distinct from
      those obtained through a linear dispersion relation of free photon. For example,
      slow light can exist, the density of state of dressed photon is non-Lorentzian
      and is very large around the energy gap; the Rabi oscillations become
      monotonically decreasing in some cases; and besides the superradiance occurs at
      long wavelengths, the spontaneous emission is also very strong near the energy
      gap because of the high density of state.

PMID- 29367749
TI  - Glucansucrase (mutant) enzymes from Lactobacillus reuteri 180 efficiently
      transglucosylate Stevia component rebaudioside A, resulting in a superior taste.
AB  - Steviol glycosides from the leaves of the plant Stevia rebaudiana are high
      potency natural sweeteners but suffer from a lingering bitterness. The
      Lactobacillus reuteri 180 wild-type glucansucrase Gtf180-DeltaN, and in
      particular its Q1140E-mutant, efficiently alpha-glucosylated rebaudioside A
      (RebA), using sucrose as donor substrate. Structural analysis of the products by
      MALDI-TOF mass spectrometry, methylation analysis and NMR spectroscopy showed
      that both enzymes exclusively glucosylate the Glc(beta1->C-19 residue of RebA,
      with the initial formation of an (alpha1->6) linkage. Docking of RebA in the
      active site of the enzyme revealed that only the steviol C-19 beta-D-glucosyl
      moiety is available for glucosylation. Response surface methodology was applied
      to optimize the Gtf180-DeltaN-Q1140E-catalyzed alpha-glucosylation of RebA,
      resulting in a highly productive process with a RebA conversion of 95% and a
      production of 115 g/L alpha-glucosylated products within 3 h. Development of a
      fed-batch reaction allowed further suppression of alpha-glucan synthesis which
      improved the product yield to 270 g/L. Sensory analysis by a trained panel
      revealed that glucosylated RebA products show a significant reduction in
      bitterness, resulting in a superior taste profile compared to RebA. The Gtf180
      DeltaN-Q1140E glucansucrase mutant enzyme thus is an efficient biocatalyst for
      generating alpha-glucosylated RebA variants with improved edulcorant/organoleptic
      properties.

PMID- 29367750
TI  - Methylphenidate regulation of osteoclasts in a dose- and sex-dependent manner
      adversely affects skeletal mechanical integrity.
AB  - Methylphenidate (MP) is the most prescribed psychostimulant for ADHD patients,
      with clinically demonstrated detrimental effects on bone quality, potentially
      leading to early onset osteoporosis and higher fracture risk. The underlying
      mechanism for the effects of MP on bone remains elusive. This study demonstrates
      that sex- and dose-dependent effects of MP on bone quality and quantity are
      mediated by osteoclast activity. Four-week-old male and female rats were treated
      with low and high dose MP for 13 weeks. Bone quality and quantity were analyzed
      using microCT, mechanical testing, histomorphometry, and TRAP staining. Male and
      female rat bone marrow-derived osteoclasts were treated in a dose-dependent
      manner (0-1000 ng/ml) and osteoclast activity was determined at days 5, 7, and 14
      using TRAP staining, as well as a pit formation assay at day 18. Animal studies
      showed a dose- and a sex-dependent decrease in mechanical integrity in femora and
      increased TRAP staining in MP-treated rats. Primary cultures revealed that MP had
      direct dose- and sex-dependent effects on osteoclast activity, as seen by
      increased differentiation, activity, and resorption. This study demonstrates for
      the first time that osteoclasts are differentially regulated by MP in adolescent
      male and female rats, resulting in sex-dependent effects on the skeleton.

PMID- 29367751
TI  - Controllable population dynamics in Landau-quantized graphene.
AB  - In this paper, we carry out a theoretical investigation on the population
      dynamics of graphene system under continuous-wave (cw) laser and chirped pulse
      excitation. Results of our numerical simulations reveal that complete population
      transfer from an initially occupied ground state to the initially unoccupied
      excited states can be achieved by choosing appropriate values of the chirp rate,
      the laser field intensity and frequency, as well as other system parameters.
      Also, we observe coherent Rabi-like population oscillations between the initial
      ground state and the excited final state. It is induced by the combined effect of
      cw and chirped-pulse laser fields. These results will contribute to the
      understanding of carrier-carrier and carrier-phonon interactions in graphene
      system, and may find applications in graphene-based high-speed electronic and
      optoelectronic devices.

PMID- 29367753
TI  - Author Correction: Orientational Mapping Augmented Sub-Wavelength Hyper-Spectral
      Imaging of Silk.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29367752
TI  - Hotspot relaxation time of NbN superconducting nanowire single-photon detectors
      on various substrates.
AB  - Hotspot relaxation time (tau th ) is one of the essential parameter which defines
      the maximum count rate of superconducting nanowire single-photon detectors
      (SNSPDs). We studied the tau th for NbN-based SNSPDs on various substrates using
      the two-photon detection method based on the pump-probe spectroscopy technique.
      We observed that tau th strongly increased with increasing bias current in the
      two-photon detection regime. In addition, the minimum hotspot relaxation time
      (tau th )min was not significantly affected by the bath temperature; this is
      different from the previous observations reported for WSi SNSPDs. In addition, a
      strong dependency of (tau th )min on the substrate was found. The minimum (tau th
      )min was 11.6 ps for SNSPDs made of 5.5-nm-thick NbN on MgO (100), whereas the
      maximum (tau th )min was 34.5 ps for SNSPDs made of 7.5-nm-thick NbN on Si (100).
      We presented a direct correlation between the values of tau th and degrees of
      disorder of NbN films grown on different substrates.

PMID- 29367754
TI  - Mitochondrial biogenesis and metabolic hyperactivation limits the application of
      MTT assay in the estimation of radiation induced growth inhibition.
AB  - Metabolic viability based high throughput assays like MTT and MTS are widely used
      in assessing the cell viability. However, alteration in both mitochondrial
      content and metabolism can influence the metabolic viability of cells and
      radiation is a potential mitochondrial biogenesis inducer. Therefore, we tested
      if MTT assay is a true measure of radiation induced cell death in widely used
      cell lines. Radiation induced cellular growth inhibition was performed by
      enumerating cell numbers and metabolic viability using MTT assay at 24 and 48
      hours (hrs) after exposure. The extent of radiation induced reduction in cell
      number was found to be larger than the decrease in MTT reduction in all the cell
      lines tested. We demonstrated that radiation induces PGC-1alpha and TFAM to
      stimulate mitochondrial biogenesis leading to increased levels of SDH-A and
      enhanced metabolic viability. Radiation induced disturbance in calcium (Ca2+)
      homeostasis also plays a crucial role by making the mitochondria hyperactive.
      These findings suggest that radiation induces mitochondrial biogenesis and
      hyperactivation leading to increased metabolic viability and MTT reduction.
      Therefore, conclusions drawn on radiation induced growth inhibition based on
      metabolic viability assays are likely to be erroneous as it may not correlate
      with growth inhibition and/or loss of clonogenic survival.

PMID- 29367755
TI  - Wild-type and mutated IDH1/2 enzymes and therapy responses.
AB  - Isocitrate dehydrogenase 1 and 2 (IDH1/2) are key enzymes in cellular metabolism,
      epigenetic regulation, redox states, and DNA repair. IDH1/2 mutations are causal
      in the development and/or progression of various types of cancer due to
      supraphysiological production of D-2-hydroxyglutarate. In various tumor types,
      IDH1/2-mutated cancers predict for improved responses to treatment with
      irradiation or chemotherapy. The present review discusses the molecular basis of
      the sensitivity of IDH1/2-mutated cancers with respect to the function of mutated
      IDH1/2 in cellular processes and their interactions with novel IDH1/2-mutant
      inhibitors. Finally, lessons learned from IDH1/2 mutations for future clinical
      applications in IDH1/2 wild-type cancers are discussed.

PMID- 29367756
TI  - PAX3-FOXO1 drives miR-486-5p and represses miR-221 contributing to pathogenesis
      of alveolar rhabdomyosarcoma.
AB  - Rhabdomyosarcoma is the most common soft-tissue sarcoma in childhood and
      histologically resembles developing skeletal muscle. Alveolar rhabdomyosarcoma
      (ARMS) is an aggressive subtype with a higher rate of metastasis and poorer
      prognosis. The majority of ARMS tumors (80%) harbor a PAX3-FOXO1 or less commonly
      a PAX7-FOXO1 fusion gene. The presence of either the PAX3-FOXO1 or PAX7-FOXO1
      fusion gene foretells a poorer prognosis resulting in clinical re-classification
      as either fusion-positive (FP-RMS) or fusion-negative RMS (FN-RMS). The PAX3/7
      FOXO1 fusion genes result in the production of a rogue transcription factors that
      drive FP-RMS pathogenesis and block myogenic differentiation. Despite knowing the
      molecular driver of FP-RMS, targeted therapies have yet to make an impact for
      patients, highlighting the need for a greater understanding of the molecular
      consequences of PAX3-FOXO1 and its target genes including microRNAs. Here we show
      FP-RMS patient-derived xenografts and cell lines display a distinct microRNA
      expression pattern. We utilized both loss- and gain-of function approaches in
      human cell lines with knockdown of PAX3-FOXO1 in FP-RMS cell lines and expression
      of PAX3-FOXO1 in human myoblasts and identified microRNAs both positively and
      negatively regulated by the PAX3-FOXO1 fusion protein. We demonstrate PAX3-FOXO1
      represses miR-221/222 that functions as a tumor suppressing microRNA through the
      negative regulation of CCND2, CDK6, and ERBB3. In contrast, miR-486-5p is
      transcriptionally activated by PAX3-FOXO1 and promotes FP-RMS proliferation,
      invasion, and clonogenic growth. Inhibition of miR-486-5p in FP-RMS xenografts
      decreased tumor growth, illustrating a proof of principle for future therapeutic
      intervention. Therefore, PAX3-FOXO1 regulates key microRNAs that may represent
      novel therapeutic vulnerabilities in FP-RMS.

PMID- 29367757
TI  - The miR-17/92 cluster is involved in the molecular etiology of the SCLL syndrome
      driven by the BCR-FGFR1 chimeric kinase.
AB  - MicroRNAs (miRNAs) have pathogenic roles in the development of a variety of
      leukemias. Here we identify miRNAs that have important roles in the development
      of B lymphomas resulting from the expression of the chimeric BCR-FGFR1 kinase.
      The miR-17/92 cluster was particularly implicated and forced expression resulted
      in increased cell proliferation, while inhibiting its function using miRNA
      sponges reduced cell growth and induced apoptosis. Cells treated with the potent
      BGJ389 FGFR1 inhibitor led to miR-17/92 downregulation, suggesting regulation by
      FGFR1. Transient luciferase reporter assays and qRT-PCR detection of endogenous
      miR-17/92 expression in stable transduced cell lines demonstrated that BCR-FGFR1
      can regulate miR-17/92 expression. This positive association of miR-17/92 with
      BCR-FGFR1 was also confirmed in primary mouse SCLL tissues and primary human CLL
      samples. miR-17/92 promotes cell proliferation and survival by targeting CDKN1A
      and PTEN in B-lymphoma cell lines and primary tumors. An inverse correlation in
      expression levels was seen between miR-17/92 and both CDKN1A and PTEN in two
      cohorts of CLL patients. Finally, in vivo engraftment studies demonstrated that
      manipulation of miR-17/92 was sufficient to affect BCR-FGFR1-driven
      leukemogenesis. Overall, our results define miR-17/92 as a downstream effector of
      FGFR1 in BCR-FGFR1-driven B-cell lymphoblastic leukemia.

PMID- 29367759
TI  - Genetic and pharmacologic abrogation of Snail1 inhibits acinar-to-ductal
      metaplasia in precursor lesions of pancreatic ductal adenocarcinoma and
      pancreatic injury.
AB  - Pancreatic cancer (PDAC) is one of the most dismal of human malignancies.
      Inhibiting or delaying the progression of precursor lesions of PDAC, pancreatic
      intraepthial neoplasia (PanINs), to invasive cancer, would be a major step. In
      the present study, we used a transgenic murine model of pancreatic cancer to
      evaluate the impact of a conditional knockout of the transcription factor Snail1,
      a major factor in epithelial-to-mesenchymal transition, on acinar-to-ductal
      formation and on PanIN progression. By interbreeding conditional LsL-Snail
      floxf/wt ; LsL-Kras G12D and Pdx1-Cre strains, we obtained LsL-Kras G12D ;Pdx1
      Cre(KP) mice, Snail1 heterozygous knockout LsL-Kras G12D ; LsL-Snail flox/- ;Pdx1
      Cre(KPShet) mice or Snail1 homozygous knockout LsL-Kras G12D ;LsL-Snail flox/flox
      ;Pdx1-Cre(KPS) mice. Mice were then followed in a longitudinal study for 2, 4, 6,
      8, 10, and 12 months. Furthermore, in mice with a genetic or pharmacological
      inhibition of Snail1, using the Snail1 inhibitor GN25, a model of pancreatic
      injury by administration of cerulein was introduced to evaluate ADM formation in
      this setting. A translational approach with a tissue microarray (TMA) of human
      PanINs and an in vivo nude mouse platform to test GN25 in human pancreatic
      adenocarcinoma was then adopted. Quantification of PanINs showed delayed
      initiation and progression of PanIN lesions at all ages in both homozygous and
      heterozygous Snaildel1;Pdx-1-Cre;LSL-KrasG12D/+-Mice. PanINs at TMA revealed
      snail expression in the majority of cases. GN25 showed growth inhibition in 2/2
      human pancreatic adenocarcinomas using a nude mice in vivo platform. Genetic and
      pharmacologic abrogation of Snail1 signaling in exocrine pancreas impairs
      development of acinar-to-ductal metaplasia following cerulein-mediated pancreatic
      injury. The present study suggests a fundamental new approach to delay the
      progression of PDAC.

PMID- 29367758
TI  - The tumor suppressor Hic1 maintains chromosomal stability independent of Tp53.
AB  - Hypermethylated-in-Cancer 1 (Hic1) is a tumor suppressor gene frequently
      inactivated by epigenetic silencing and loss-of-heterozygosity in a broad range
      of cancers. Loss of HIC1, a sequence-specific zinc finger transcriptional
      repressor, results in deregulation of genes that promote a malignant phenotype in
      a lineage-specific manner. In particular, upregulation of the HIC1 target gene
      SIRT1, a histone deacetylase, can promote tumor growth by inactivating TP53. An
      alternate line of evidence suggests that HIC1 can promote the repair of DNA
      double strand breaks through an interaction with MTA1, a component of the
      nucleosome remodeling and deacetylase (NuRD) complex. Using a conditional
      knockout mouse model of tumor initiation, we now show that inactivation of Hic1
      results in cell cycle arrest, premature senescence, chromosomal instability and
      spontaneous transformation in vitro. This phenocopies the effects of deleting
      Brca1, a component of the homologous recombination DNA repair pathway, in mouse
      embryonic fibroblasts. These effects did not appear to be mediated by
      deregulation of Hic1 target gene expression or loss of Tp53 function, and rather
      support a role for Hic1 in maintaining genome integrity during sustained
      replicative stress. Loss of Hic1 function also cooperated with activation of
      oncogenic KRas in the adult airway epithelium of mice, resulting in the formation
      of highly pleomorphic adenocarcinomas with a micropapillary phenotype in vivo.
      These results suggest that loss of Hic1 expression in the early stages of tumor
      formation may contribute to malignant transformation through the acquisition of
      chromosomal instability.

PMID- 29367760
TI  - ROS release by PPARbeta/delta-null fibroblasts reduces tumor load through
      epithelial antioxidant response.
AB  - Tumor stroma has an active role in the initiation, growth, and propagation of
      many tumor types by secreting growth factors and modulating redox status of the
      microenvironment. Although PPARbeta/delta in fibroblasts was shown to modulate
      oxidative stress in the wound microenvironment, there has been no evidence of a
      similar effect in the tumor stroma. Here, we present evidence of oxidative stress
      modulation by intestinal stromal PPARbeta/delta, using a FSPCre-Pparb/d-/- mouse
      model and validated it with immortalized cell lines. The FSPCre-Pparb/d-/- mice
      developed fewer intestinal polyps and survived longer when compared with
      Pparb/dfl/fl mice. The pre-treatment of FSPCre-Pparb/d-/- and Pparb/dfl/fl with
      antioxidant N-acetyl-cysteine prior DSS-induced tumorigenesis resulted in lower
      tumor load. Gene expression analyses implicated an altered oxidative stress
      processes. Indeed, the FSPCre-Pparb/d-/- intestinal tumors have reduced oxidative
      stress than Pparb/dfl/fl tumors. Similarly, the colorectal cancer cells and human
      colon epithelial cells also experienced lower oxidative stress when co-cultured
      with fibroblasts depleted of PPARbeta/delta expression. Therefore, our results
      establish a role for fibroblast PPARbeta/delta in epithelial-mesenchymal
      communication for ROS homeostasis.

PMID- 29367761
TI  - Hypoxia induces miR-153 through the IRE1alpha-XBP1 pathway to fine tune the
      HIF1alpha/VEGFA axis in breast cancer angiogenesis.
AB  - It is well documented that hypoxia activates the hypoxia-inducible factor 1-alpha
      (HIF1alpha)/vascular endothelial growth factor A (VEGFA) axis to promote
      angiogenesis in breast cancer. However, it is unclear how this axis is negatively
      regulated. In this study, we demonstrated that miR-153 directly inhibits
      expression of HIF1alpha by binding to the 3'UTR of HIF1A mRNA, as well as
      suppresses tube formation of primary human umbilical vein endothelial cells
      (HUVECs) and breast cancer angiogenesis by decreasing the secretion of VEGFA.
      Importantly, expression of miR-153 was induced by hypoxia-stimulated ER stress,
      which activates IRE1alpha and its downstream transcription factor X-box binding
      protein 1 (XBP1). X-box binding protein 1 directly binds to the promoter of the
      miR-153 host gene PTPRN and activates transcription. These results indicate that
      hypoxia induces miR-153 to fine tune the HIF1alpha/VEGFA axis in breast cancer
      angiogenesis and miR-153 could be used for breast cancer anti-angiogenesis
      therapy.

PMID- 29367762
TI  - Suppression of STING signaling through epigenetic silencing and missense mutation
      impedes DNA damage mediated cytokine production.
AB  - The production of cytokines in response to DNA-damage events may be an important
      host defense response to help prevent the escape of pre-cancerous cells. The
      innate immune pathways involved in these events are known to be regulated by
      cellular molecules such as stimulator of interferon genes (STING), which controls
      type I interferon and pro-inflammatory cytokine production in response to the
      presence of microbial DNA or cytosolic DNA that has escaped from the nucleus.
      STING signaling has been shown to be defective in a variety of cancers, such as
      colon cancer and melanoma, actions that may enable damaged cells to escape the
      immunosurveillance system. Here, we report through examination of databases that
      STING signaling may be commonly suppressed in a greater variety of tumors due to
      loss-of-function mutation or epigenetic silencing of the STING/cGAS promoter
      regions. In comparison, RNA activated innate immune pathways controlled by RIG
      I/MDA5 were significantly less affected. Examination of reported missense STING
      variants confirmed that many exhibited a loss-of-function phenotype and could not
      activate cytokine production following exposure to cytosolic DNA or DNA-damage
      events. Our data imply that the STING signaling pathway may be recurrently
      suppressed by a number of mechanisms in a considerable variety of malignant
      disease and be a requirement for cellular transformation.

PMID- 29367763
TI  - Network analysis of SRC-1 reveals a novel transcription factor hub which
      regulates endocrine resistant breast cancer.
AB  - Steroid receptor coactivator 1 (SRC-1) interacts with nuclear receptors and other
      transcription factors (TFs) to initiate transcriptional networks and regulate
      downstream genes which enable the cancer cell to evade therapy and metastasise.
      Here we took a top-down discovery approach to map out the SRC-1 transcriptional
      network in endocrine resistant breast cancer. First, rapid immunoprecipitation
      mass spectrometry of endogenous proteins (RIME) was employed to uncover new SRC-1
      TF partners. Next, RNA sequencing (RNAseq) was undertaken to investigate SRC-1 TF
      target genes. Molecular and patient-derived xenograft studies confirmed STAT1 as
      a new SRC-1 TF partner, important in the regulation of a cadre of four SRC-1
      transcription targets, NFIA, SMAD2, E2F7 and ASCL1. Extended network analysis
      identified a downstream 79 gene network, the clinical relevance of which was
      investigated in RNAseq studies from matched primary and local-recurrence tumours
      from endocrine resistant patients. We propose that SRC-1 can partner with STAT1
      independently of the estrogen receptor to initiate a transcriptional cascade and
      control regulation of key endocrine resistant genes.

PMID- 29367764
TI  - Blockade of insulin-like growth factors increases efficacy of paclitaxel in
      metastatic breast cancer.
AB  - Breast cancer remains the leading cause of cancer death in women owing to
      metastasis and the development of resistance to established therapies.
      Macrophages are the most abundant immune cells in the breast tumor
      microenvironment and can both inhibit and support cancer progression. Thus,
      gaining a better understanding of how macrophages support cancer could lead to
      the development of more effective therapies. In this study, we find that breast
      cancer-associated macrophages express high levels of insulin-like growth factors
      1 and 2 (IGFs) and are the main source of IGFs within both primary and metastatic
      tumors. In total, 75% of breast cancer patients show activation of insulin/IGF-1
      receptor signaling and this correlates with increased macrophage infiltration and
      advanced tumor stage. In patients with invasive breast cancer, activation of
      Insulin/IGF-1 receptors increased to 87%. Blocking IGF in combination with
      paclitaxel, a chemotherapeutic agent commonly used to treat breast cancer, showed
      a significant reduction in tumor cell proliferation and lung metastasis in pre
      clinical breast cancer models compared to paclitaxel monotherapy. Our findings
      provide the rationale for further developing the combination of paclitaxel with
      IGF blockers for the treatment of invasive breast cancer, and Insulin/IGF1R
      activation and IGF+ stroma cells as potential biomarker candidates for further
      evaluation.

PMID- 29367765
TI  - Employing mesenchymal stem cells to support tumor-targeted delivery of
      extracellular vesicle (EV)-encapsulated microRNA-379.
AB  - Adult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing
      capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs
      secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in
      intercellular communication. The aim of this study was to characterize a
      potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs
      enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression
      was significantly reduced in lymph node metastases compared to primary tumor
      tissue from the same patients. A significant reduction in the rate of tumor
      formation and growth in vivo was observed in T47D breast cancer cells stably
      expressing miR-379. In more aggressive HER2-amplified HCC-1954 cells, HCC-379 and
      HCC-NTC tumor growth rate in vivo was similar, but increased tumor necrosis was
      observed in HCC-379 tumors. In response to elevated miR-379, COX-2 mRNA and
      protein was also significantly reduced in vitro and in vivo. MSCs were
      successfully engineered to secrete EVs enriched with miR-379, with the majority
      found to be of the appropriate size and morphology of exosomal EVs.
      Administration of MSC-379 or MSC-NTC cells, or EVs derived from either cell
      population, resulted in no adverse effects in vivo. While MSC-379 cells did not
      impact tumor growth, systemic administration of cell-free EVs enriched with miR
      379 was demonstrated to have a therapeutic effect. The data presented support miR
      379 as a potent tumor suppressor in breast cancer, mediated in part through
      regulation of COX-2. Exploiting the tumor-homing capacity of MSCs while
      engineering the cells to secrete EVs enriched with miR-379 holds exciting
      potential as an innovative therapy for metastatic breast cancer.

PMID- 29367766
TI  - PTEN loss in the fallopian tube induces hyperplasia and ovarian tumor formation.
AB  - The signaling events involved in the onset of ovarian cancer from the fallopian
      tube epithelium (FTE) are crucial for early detection and treatment of the
      disease, but they remain poorly defined. Conditional homozygous knockout of PTEN
      mediated by PAX8-cre recombinase was sufficient to drive endometrioid and serous
      borderline ovarian carcinoma, providing the first model of FTE-derived borderline
      tumors. In addition, heterozygous PTEN deletion in the FTE resulted in
      hyperplasia, providing a model to study early events of human ovarian
      pathogenesis. To uncover the mechanism underlying the invasion of cancerous
      oviductal cells to the ovary, PTEN-deficient murine oviductal cells were
      developed and tagged with green fluorescent protein. Loss of PTEN increased cell
      migration, invasion, and upregulated WNT4, a key regulator of Mullerian duct
      development during embryogenesis. Further investigation revealed that WNT4 was
      required for increased migration and colonization of the ovary by PTEN-deficient
      oviductal cells in a beta-catenin independent manner. Human tumor microarrays and
      ovarian cancer cells lines confirmed WNT4 expression in cancer and its role in
      migration. Together, these findings provide a novel model to study the mechanism
      of fallopian tube tumor initiation and invasion to the ovary mediated by loss of
      PTEN, which may help to define early events of human ovarian carcinogenesis.

PMID- 29367768
TI  - Components of a Measure to Describe Organizational Culture in Academic Pharmacy.
AB  - Objective. To develop a measure of organizational culture in academic pharmacy
      and identify characteristics of an academic pharmacy program that would be
      impactful for internal (eg, students, employees) and external (eg, preceptors,
      practitioners) clients of the program. Methods. A three-round Delphi procedure of
      24 panelists from pharmacy schools in the U.S. and Canada generated items based
      on the Organizational Culture Profile (OCP), which were then evaluated and
      refined for inclusion in subsequent rounds. Items were assessed for
      appropriateness and impact. Results. The panel produced 35 items across six
      domains that measured organizational culture in academic pharmacy:
      competitiveness, performance orientation, social responsibility, innovation,
      emphasis on collegial support, and stability. Conclusion. The items generated
      require testing for validation and reliability in a large sample to finalize this
      measure of organizational culture.

PMID- 29367767
TI  - A Carcinogen-induced mouse model recapitulates the molecular alterations of human
      muscle invasive bladder cancer.
AB  - The N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model is an attractive
      model system of muscle-invasive bladder cancer (MIBC) as it recapitulates the
      histology of human tumors in a background with intact immune system. However, it
      was unknown whether this carcinogen-induced model also mimicked human MIBC at the
      molecular and mutational level. In our study, we analyzed gene expression and
      mutational landscape of the BBN model by next-generation sequencing followed by a
      bioinformatic comparison to human MIBC using data from The Cancer Genome Atlas
      and other repositories. BBN tumors showed overexpression of markers of basal
      cancer subtype, and had a high mutation burden with frequent Trp53 (80%), Kmt2d
      (70%), and Kmt2c (90%) mutations by exome sequencing, similar to human MIBC. Many
      variants corresponded to human cancer hotspot mutations, supporting their role as
      driver mutations. We extracted two novel mutational signatures from the BBN mouse
      genomes. The integrated analysis of mutation frequencies and signatures
      highlighted the contribution of aberrations to chromatin regulators and genetic
      instability in the BBN tumors. Together, our study revealed several similarities
      between human MIBC and the BBN mouse model, providing a strong rationale for its
      use in molecular and drug discovery studies.

PMID- 29367769
TI  - Assessment of Learner Metacognition in a Professional Pharmacy Elective Course.
AB  - Objective. To investigate the effect of strategic feedback and metacognitive
      processes on learners' ability to predict performance and improve self-awareness.
      Methods. Strategic faculty and peer feedback, as well as self-assessments, were
      implemented in a professional pharmacy elective course throughout the semester,
      focused on three case-based oral presentations. After each presentation, students
      utilized an objective rubric to determine self-predicted and peer-predicted
      scores. Actual scores from faculty were compared to students' predicted scores.
      Results. Students' ability to predict presentation scores did not improve over
      time; however, students were able to accurately estimate performance in certain
      rubric sections on individual presentations (depth of problem, presentation).
      Students were generally overconfident in predicting their performance. When
      broken down into tertiles, top performing students were more accurate in their
      self-assessments compared to bottom performing students. Bottom performing
      students were highly overconfident in their assessment. Conclusion. Self
      awareness is essential for professionals, though difficult to cultivate and
      improve in one semester. Incorporating longitudinal, continuous feedback and
      metacognitive skills may help learners become more aware of their own performance
      and devise a plan for enhancement.

PMID- 29367770
TI  - Contemporary Professional Skills Development for Pharmacists in the Middle East.
AB  - Objective. To determine professional skills development and its utility among the
      "bridge" curriculum for undergraduate and graduate students in the Middle East.
      Methods. Qatar University College of Pharmacy offers a part-time Doctor of
      Pharmacy (PharmD) program for licensed pharmacists, which includes pre-internship
      or "bridge" courses adapted from the undergraduate baccalaureate program.
      Assessments for all professional skills courses delivered in the undergraduate
      and post-baccalaureate part-time PharmD curriculums between 2011 and 2015
      academic years were inventoried. The number and nature of assignments and exams
      administered to both student cohorts were identified and aggregate class scores
      recorded. Results were compared using Mann-Whitney tests for non-parametric
      continuous data with significance level (2-sided) set at alpha <.05. Results.
      Twenty-seven common assessments were conducted over a 5-year period. Overall, the
      performance between the undergraduate and graduate students was comparable except
      for specific assignments and in certain cohorts. Chart note documentation skills
      were poor among part-time PharmD students in both professional skills years and
      may be attributed to lack of prior instruction or current use in practice.
      Conclusion. Our comparison of graduate and undergraduate student performance in a
      professional skills course series has reinforced its legitimacy in our part-time
      PharmD bridge curriculum. Such quality assurance is relevant for programs
      offering advanced degree training for licensed professionals to ensure ongoing
      alignment of student abilities with desired educational outcomes and ultimately,
      delivery of patient care.

PMID- 29367771
TI  - A Qualitative Study Designed to Build an Experiential Education Curriculum for
      Practice-Ready Community Pharmacy-Bound Students.
AB  - Objective. To design an experiential education curriculum that sequentially and
      deliberately prepares community pharmacy-bound graduates to practice at the level
      of the care provider and display the skills needed to be a pharmacist-in-charge.
      Methods. Semi-structured interviews were conducted with community pharmacy
      stakeholders. Transcriptions from the interviews were analyzed to identify common
      themes in needed community pharmacy training for core and elective advanced
      pharmacy practice experiences (APPEs). The themes were used to distinguish key
      elements of a community pharmacy experiential education curriculum that would
      meet the project objective. Results. Forty-two individuals were interviewed: 11
      were interviewed individually and 31 in focus groups, with each group comprising
      two to six individuals. There were 11 focus groups. Theme analysis allowed
      differentiation of activities and performance levels for the community pharmacy
      introductory pharmacy practice experience (IPPE) and the core APPE as well as the
      goal of the core APPE for all program graduates. Participants identified two
      important elective APPEs for students planning to practice in community pharmacy
      after graduation: an advanced patient care experience and a management
      experience. Participants emphasized the importance of sequencing the core and
      advanced elective APPEs so that the advanced electives could build upon the
      skills demonstrated in the core APPE. Participants identified knowledge, skills,
      and attitudes needed for practice-readiness upon graduation. Conclusion. The
      identified experiential education curriculum for students planning to practice in
      the community pharmacy setting upon graduation will prepare them to provide care
      to complex community-dwelling patients and function as a pharmacist-in-charge in
      this setting.

PMID- 29367772
TI  - Design and Implementation of an Elective on the Ethnopharmacology of Appalachia
      for the PharmD Curriculum.
AB  - Objective. To create and implement a class in ethnopharmacology that would
      educate student pharmacists on folk medicine, including home remedies and native
      plants that are used as alternative medicinal sources; active components of
      medicinal plants including toxicity issues and the mechanism of action of
      beneficial compounds, such as catechins and other flavonoids; and nutraceuticals
      and poisonous plants. Methods. In this three-credit hour class, herbal remedies
      are investigated from the standpoints of medical efficacy, potential toxicities
      and drug interactions with prescribed medications. Class discussions are
      conducted on the usefulness of remedies, the attitudes of practitioners toward
      traditional remedy use and the risks of relying on herbal preparations. Each
      student prepares a 15-minute presentation on a disease state, which covers modern
      pharmaceuticals and herbal or folk remedy alternatives used in that disease.
      Special emphasis is given to drug-herb interactions. Results. The class has
      gained popularity among students and consistently fills within the first hour of
      computerized registration. Students agree that being educated in the benefits and
      potential toxicities of herbal products will better prepare them to counsel their
      patients who use these remedies. The elective has been offered 10 times since
      2007. Anecdotal comments from our alumni indicate that they have found the
      information to be very useful in their practice environments. Conclusion.
      Providing our students with a greater understanding of herbal remedies is
      essential to prepare them for practice. By including both the uses and potential
      toxicities, the student pharmacist is able to counsel her patients from a
      standpoint of expertise on these self-administered remedies.

PMID- 29367773
TI  - Pharmacy Residency School-wide Match Rates and Modifiable Predictors in ACPE
      accredited Colleges and Schools of Pharmacy.
AB  - Objective. To analyze the modifiable predictors of institution-wide residency
      match rates. Methods. This was a retrospective analysis of colleges and schools
      of pharmacy data and school-wide PGY-1 pharmacy residency match rates for 2013
      through 2015. Independent variables included NAPLEX passing rates, history of
      ACPE probation, NIH funding, academic health center affiliation, dual-degree
      availability, program length, admit-to-applicant ratio, class size, tuition,
      student-driven research, clinically focused academic tracks, residency
      affiliation, U.S. News & World Report rankings, and minority enrollment. Results.
      In a repeated measures model, predictors of match results were NAPLEX pass rate,
      class size, academic health center affiliation, admit-to-applicant ratio, U.S.
      News & World Report rankings, and minority enrollment. Conclusion. Indicators of
      student achievement, college/school reputation, affiliations, and class
      demographics were significant predictors of institution-wide residency match
      rates. Further research is needed to understand how changes in these factors may
      influence overall match rates.

PMID- 29367774
TI  - Pharmacists' Opinions of the Value of CAPE Outcomes in Hiring Decisions.
AB  - Objective. The Hiring Intent Reasoning Examination (HIRE) was designed to explore
      the utility of the CAPE 2013 outcomes attributes from the perspective of
      practicing pharmacists, examine how each attribute influences hiring decisions,
      and identify which of the attributes are perceived as most and least valuable by
      practicing pharmacists. Methods. An electronic questionnaire was developed and
      distributed to licensed pharmacists in four states to collect their opinions
      about 15 CAPE subdomains plus five additional business related attributes. The
      attributes that respondents identified were: necessary to be a good pharmacist,
      would impact hiring decisions, most important to them, and in short supply in the
      applicant pool. Data were analyzed using statistical analysis software to
      determine the relative importance of each to practicing pharmacists and various
      subsets of pharmacists. Results. The CAPE subdomains were considered necessary
      for most jobs by 51% or more of the 3723 respondents (range, 51% to 99%). The
      necessity for business-related attributes ranged from 21% to 92%. The percentage
      who would not hire an applicant who did not possess the attribute ranged from 2%
      to 71.5%; the percentage who considered the attribute most valuable ranged from
      0.3% to 35%; and the percentage who felt the attribute was in short supply ranged
      from 5% to 36%. Opinions varied depending upon gender, practice setting and
      whether the pharmacist was an employee or employer. Conclusion. The results of
      this study can be used by faculty and administrators to inform curricular design
      and emphasis on CAPE domains and business-related education in pharmacy programs.

PMID- 29367775
TI  - Cost-Effectiveness of Using Standardized Patients to Assess Student-Pharmacist
      Communication Skills.
AB  - Objective. To explore the cost-effectiveness of including standardized patients
      (SP) in the didactic curriculum for application and assessment of students'
      pharmacist-patient communication skills. Methods. Five role play/case study
      (RP/CS) activities from a communication skills curriculum were replaced with five
      SP encounters. Communication was assessed using a rubric. This study developed an
      economic model to examine the costs and effectiveness of replacing RP/CS events
      with SP events in knowledge-application and communication assessment. Costs
      consisted of SP hourly wages for training and delivery of SP events. Outcomes
      examined were the incremental cost-effectiveness ratio (ICER) per student.
      Results. The ICER comparing SP to RP/CS was $100.93 higher per student on first
      attempt pass rates and $9.04 per one-point increase in the mean score.
      Conclusion. SP was more effective and more costly than RP/CS. Further research
      into students' willingness to pay needs to occur before determining if using SPs
      is cost-effective in teaching communication skills.

PMID- 29367776
TI  - Evaluation of a Unique Interprofessional Education Program Involving Medical and
      Pharmacy Students.
AB  - Objective. To measure changes in interprofessional competencies among pharmacy
      and medical students following a half-day event focusing on interprofessional
      learning. Methods. There were 118 pharmacy students and 28 medical students who
      participated in the Healthcare Interprofessional Education Day (HIPED) which
      consisted of three stations (communication, patient interviewing, and
      prescribing) in which pharmacy and medical students had to work collaboratively.
      The standardized Interprofessional Collaborative Competency Attainment Survey
      (ICCAS) was used to evaluate the effectiveness of the program. Results. There
      were 133 surveys completed for a response rate of 91%. All 20 items measured by
      the ICCAS showed a significant improvement. The strongest effect sizes were in
      the collaboration, roles & responsibilities, and collaborative practice/family
      centered approach categories. The least robust effects were in the conflict
      management/resolution category. Conclusion. The HIPED activity was an effective
      IPE experience. The strong and consistent improvement in all ICCAS scores suggest
      a framework for pharmacy and medical school training to move from siloed
      educational experiences to synergistic learning opportunities.

PMID- 29367777
TI  - Impact of Pre-Pharmacy Work Experience on Development of Professional Identity in
      Student Pharmacists.
AB  - Objective. To determine the benefit of pharmacy work experience on the
      development of student pharmacists' professional identity. Methods. Students in
      all four professional years were surveyed using a validated Professional Self
      identity Questionnaire (PSIQ). They were also asked about pharmacy experience
      prior to matriculation and their performance on Drug Information tests given
      midway through the P1 year and at the beginning of the P3 year. PSIQ responses
      and test results were compared based on pharmacy experience. Results. The PSIQ
      was completed by 293 student pharmacists, for a 67% response rate, with 76% of
      respondents reporting pharmacy experience prior to matriculation. Statistically
      higher scores on responses to 6 of the 9 PSIQ Likert-type items were observed
      from students in the first professional year for those with pharmacy experience;
      however, only one item in the second year showed differences with none in the
      third and fourth years. No impact of experience was observed on Top 100 or Top
      300 grades. Conclusion. Pre-matriculation pharmacy experience may increase
      development of professional identity early in the student experience but may have
      little impact on academic readiness. Schools and colleges of pharmacy hoping to
      recruit students with an early sense of professional identity should consider
      adding such experience to their admissions requirements.

PMID- 29367778
TI  - Design and Implementation of a Professional Development Course Series.
AB  - Objective. To design and implement a longitudinal course series focused on
      professional development and professional identity formation in pharmacy students
      at Western New England University. Methods. A four-year, theme-based course
      series was designed to sequentially and longitudinally impart the values,
      attributes, and characteristics of a professional pharmacist. Requirements of the
      course include: goal planning and reflective assignments, submission of "Best
      Works," attendance at professional meetings, completion of service hours, annual
      completion of a Pharmacy Professionalism Instrument, attendance at Dean's
      Seminar, participation in roundtable discussions, and maintenance of an
      electronic portfolio. Though the Professional Development course series carries
      no credit, these courses are progression requirements and students are assessed
      on a pass/fail basis. Results. Course pass rates in the 2015-2016 academic year
      for all four classes were 99% to 100%, suggesting the majority of students take
      professional development seriously and are achieving the intended outcomes of the
      courses. Conclusion. A professional development course series was designed and
      implemented in the new Doctor of Pharmacy program at Western New England
      University to enhance the professional identity formation of students.

PMID- 29367779
TI  - Design and Evaluation of Video Podcasts for Providing Online Feedback on
      Formative Pharmaceutical Calculations Assessments.
AB  - Objective. To evaluate worked example video podcasts as a method of providing
      feedback to pharmacy interns for an online and formative pharmaceutical
      calculations assessment. Methods. A theory-informed approach based on multimedia
      learning theory was used to design video podcasts as feedback on a calculations
      examination. A mixed-methods evaluation completed by pharmacy interns enrolled in
      Ireland's National Pharmacy Internship Programme was used to establish cognitive
      and affective attitudes toward video podcasts compared with conventional written
      solutions. Results. The majority of students found video podcasts were clear,
      helpful for learning, easy to understand, and useful as a method of feedback.
      Majority reported that they felt positively about standard written solutions. The
      evaluation suggested distinct benefits for each kind of feedback, something that
      has not been previously reported. Thematic analysis of qualitative data indicated
      useful features of video podcasts, including clear explanation, step-by-step
      approach, and synchronization of audio and visual information. Conclusion.
      Respondents reported positive cognitive and affective attitudes toward video
      podcasts as online feedback. Video podcasts are a helpful and novel way of
      providing feedback on pharmaceutical calculations. A similar opinion of
      traditional written solutions suggests that students may benefit from both forms
      of feedback. Further study is required to identify the particular benefits
      associated with both kinds.

PMID- 29367780
TI  - Marking our Milestones: Address of the 2016-2017 President to the Opening General
      Session at the 2017 Annual Meeting.

PMID- 29367781
TI  - Dietary Supplement Use, Knowledge, and Perceptions Among Student Pharmacists.

PMID- 29367782
TI  - Response to Dietary Supplement Use, Knowledge, and Perceptions Among Student
      Pharmacists.

PMID- 29367783
TI  - Help! Dean Drowning in Survey Requests.

PMID- 29367784
TI  - Purposeful Global Engagement in Pharmacy Education.

PMID- 29367786
TI  - The Psychological Assessment of Clerics.
AB  - The psychological assessment of novice and experienced clerics is an important
      component of ordination, suitability, and risk evaluation to ensure that
      representatives of religious organizations are equipped, motivated, and safe for
      a life commitment to a faith vocation. It is the authors' opinion that such
      assessments should be conducted by skilled psychologists with expertise that
      covers occupational, clinical, and forensic domains. Further, the authors
      emphasize the importance of an objective and secular assessment to better inform
      the church about its role and responsibility for the oversight and spiritual
      development of the cleric. A thorough psychological assessment should incorporate
      a multimodal approach to information gathering, which includes a comprehensive
      review of background information and medical records, a personal history
      interview, a mental status examination, and administration of relevant
      psychometric measures and assessment tools. We also advise that, upon completion
      of the assessment, the requesting religious organization should be offered the
      opportunity to meet with the evaluating psychologist to discuss suitability
      issues and, if necessary, risk management planning.

PMID- 29367785
TI  - Image Correspondence: Cover Image: Detection of hair follicleassociated Merkel
      cell polyomavirus in an immunocompromised host with follicular spicules and
      alopecia.

PMID- 29367787
TI  - Zinc Removal from the Aqueous Solutions by the Chemically Modified Biosorbents.
AB  - Biosorbents are the natural origin adsorbents, which popularity in environmental
      engineering is steadily increasing due to their low price, ease of acquisition,
      and lack of the toxic properties. Presented research aimed to analyze the
      possibility of chemical modification of the straw, which is a characteristic
      waste in the Polish agriculture, to improve its biosorption properties with
      respect to removal of selected metals from aquatic solutions. Biosorbents used
      during the tests was a barley straw that was shredded to a size in the range of
      0.2-1.0 mm. The biosorption process was performed for aqueous solutions of zinc
      at a pH 5. Two different modifications of straw were analyzed: esterification
      with methanol and modification using the citric acid at elevated temperature. The
      results, obtained during the research, show a clear improvement in sorption
      capacity of the straw modified by the citric acid. In the case of straw modified
      with methanol, it has been shown that the effectiveness of zinc biosorption
      process was even a twice lower with respect to the unmodified straw. Moreover, it
      was concluded that the removal of analyzed metals was based mainly on the ion
      exchange adsorption mechanism by releasing a calcium and magnesium ions from the
      straw surface to the solution. Graphical Abstract?.

PMID- 29367788
TI  - Effect of Silene vulgaris and Heavy Metal Pollution on Soil Microbial Diversity
      in Long-Term Contaminated Soil.
AB  - In this study, we analysed the impact of heavy metals and plant rhizodeposition
      on the structure of indigenous microbial communities in rhizosphere and bulk soil
      that had been exposed to heavy metals for more than 150 years. Samples of the
      rhizosphere of Silene vulgaris and non-rhizosphere soils 250 and 450 m from the
      source of emission that had different metal concentrations were collected for
      analyses. The results showed that soils were collected 250 m from the smelter had
      a higher number of Cd-resistant CFU compared with the samples that were collected
      from 450 m, but no significant differences were observed in the number of total
      and oligotrophic CFU or the equivalent cell numbers between rhizosphere and non
      rhizosphere soils that were taken 250 and 450 m from the emitter. Unweighted pair
      group method with arithmetic mean (UPGMA) cluster analysis of the denaturing
      gradient gel electrophoresis (DGGE) profiles, as well as a cluster analysis that
      was generated on the phospholipid fatty acid (PLFA) profiles, showed that the
      bacterial community structure of rhizosphere soils depended more on the plant
      than on the distance and metal concentrations. The sequencing of the 16S rDNA
      fragments that were excised from the DGGE gel revealed representatives of the
      phyla Bacteroidetes, Acidobacteria, Gemmatimonadetes, Actinobacteria and
      Betaproteobacteria in the analysed soil with a predominance of the first three
      groups. The obtained results demonstrated that the presence of S. vulgaris did
      not affect the number of CFUs, except for those of Cd-resistant bacteria.
      However, the presence of S. vulgaris altered the soil bacterial community
      structure, regardless of the sampling site, which supported the thesis that
      plants have a higher impact on soil microbial community than metal contamination.

PMID- 29367789
TI  - Stimulation of Heavy Metal Adsorption Process by Using a Strong Magnetic Field.
AB  - The adsorption process is one of the most important techniques of water and
      wastewater treatment technology. Therefore, there are many methods allowing to
      improve the effectiveness of these processes based mainly on the chemical
      modification of adsorbents. However, they are always associated with the
      necessity of introducing an additional wastes or sewage to the environment. That
      is why a purpose of the presented was to investigate an innovative and
      noninvasive adsorption supporting method based on the using of a static magnetic
      field. The results showed that in the adsorption process of equimolar copper,
      nickel, and cadmium mixture, a presence of the magnetic field may increase the
      effectiveness of the process, with respect to copper by more than 40% and a
      summary molar removal was increased about 11%. However, the effectiveness of the
      analyzed modification depends largely on the heavy metal equilibrium
      concentration, and when it increases, a beneficial effect of magnetic field
      significantly decreases. Nevertheless, due to the fact that heavy metal
      adsorption processes are very important part of environmental engineering
      technologies, it can be assumed that further work on magnetic modification of
      these processes can allow for a significant improvement of many water and
      wastewater purification plants. Graphical Abstract.

PMID- 29367790
TI  - Volatile organic compound emissions from Alnus glutinosa under interacting
      drought and herbivory stresses.
AB  - Plant volatile organic compounds (VOCs) elicited in response to herbivory can
      serve as cues for parasitic and predatory insects, but the modification of VOC
      elicitation responses under interacting abiotic stresses is poorly known. We
      studied foliage VOC emissions in the deciduous tree Alnus glutinosa induced by
      feeding by the larvae of green alder sawfly (Monsoma pulveratum) under well
      watered and drought-stressed conditions. Drought strongly curbed photosynthesis
      rate and stomatal conductance, but there were no effects of insect feeding on
      photosynthetic characteristics. Feeding induced emissions of volatile products of
      lipoxygenase pathway and monoterpenes, and emissions of stress marker compounds
      (E)-beta-ocimene and homoterpene DMNT. The emissions were more strongly elicited
      and reached a maximum value earlier in drought-stressed plants. In addition,
      methyl salicylate emissions were elicited in herbivory-fed drought-stressed
      plants. Herbivores were more strongly attracted to well-watered plants and
      consumed more than a four-fold greater fraction of leaf area than they consumed
      from drought-treated plants. Overall, this study demonstrates an important
      priming effect of drought, suggesting that plants under combined
      drought/herbivory stress are more resistant to herbivores.

PMID- 29367791
TI  - Mono- and sesquiterpene release from tomato (Solanum lycopersicum) leaves upon
      mild and severe heat stress and through recovery: from gene expression to
      emission responses.
AB  - Plants frequently experience heat ramps of various severities, but how and to
      what degree plant metabolic activity recovers from mild and severe heat stress is
      poorly understood. In this study, we exposed the constitutive terpene emitter,
      Solanum. lycopersicum leaves to mild (37 and 41  degrees C), moderate (46 
      degrees C) and severe (49  degrees C) heat ramps of 5 min. and monitored foliage
      photosynthetic activity, lipoxygenase pathway volatile (LOX), and mono- and
      sesquiterpene emissions and expression of two terpene synthase genes, beta
      phellandrene synthase and (E)-beta-caryophyllene/alpha-humulene synthase, through
      a 24 h recovery period upon return to pre-stress conditions. Leaf monoterpene
      emissions were dominated by beta-phellandrene and sesquiterpene emissions by (E)
      beta-caryophyllene, and thus, these two terpene synthase genes were
      representative for the two volatile terpene classes. Photosynthetic
      characteristics partly recovered under moderate heat stress, and very limited
      recovery was observed under severe stress. All stress treatments resulted in
      elicitation of LOX emissions that declined during recovery. Enhanced mono- and
      sesquiterpene emissions were observed immediately after the heat treatment, but
      the emissions decreased even to below the control treatment during recovery
      between 2-10 h, and raised again by 24 h. The expression of beta-phellandrene and
      (E)-beta-caryophyllene synthase genes decreased between 2-10 h after heat stress,
      and recovered to pre-stress level in mild heat stress treatment by 24 h. Overall,
      this study demonstrates a highly sensitive heat response of terpenoid synthesis
      that is mainly controlled by gene level responses under mild stress, while severe
      stress leads to non-recoverable declines in foliage physiological and gene
      expression activities.

PMID- 29367792
TI  - Disproportionate photosynthetic decline and inverse relationship between
      constitutive and induced volatile emissions upon feeding of Quercus robur leaves
      by large larvae of gypsy moth (Lymantria dispar).
AB  - Gypsy moth (Lymantria dispar L., Lymantriinae) is a major pest of pedunculate oak
      (Quercus robur) forests in Europe, but how its infections scale with foliage
      physiological characteristics, in particular with photosynthesis rates and
      emissions of volatile organic compounds has not been studied. Differently from
      the majority of insect herbivores, large larvae of L. dispar rapidly consume leaf
      area, and can also bite through tough tissues, including secondary and primary
      leaf veins. Given the rapid and devastating feeding responses, we hypothesized
      that infection of Q. robur leaves by L. dispar leads to disproportionate scaling
      of leaf photosynthesis and constitutive isoprene emissions with damaged leaf
      area, and to less prominent enhancements of induced volatile release. Leaves with
      0% (control) to 50% of leaf area removed by larvae were studied. Across this
      range of infection severity, all physiological characteristics were
      quantitatively correlated with the degree of damage, but all these traits changed
      disproportionately with the degree of damage. The net assimilation rate was
      reduced by almost 10-fold and constitutive isoprene emissions by more than 7
      fold, whereas the emissions of green leaf volatiles, monoterpenes, methyl
      salicylate and the homoterpene (3E)-4,8-dimethy-1,3,7-nonatriene scaled
      negatively and almost linearly with net assimilation rate through damage
      treatments. This study demonstrates that feeding by large insect herbivores
      disproportionately alters photosynthetic rate and constitutive isoprene
      emissions. Furthermore, the leaves have a surprisingly large capacity for
      enhancement of induced emissions even when foliage photosynthetic function is
      severely impaired.

PMID- 29367794
TI  - Heterogeneity and Cooperation: The Role of Capability and Valuation on Public
      Goods Provision.
AB  - We experimentally investigate the effects of two different sources of
      heterogeneity - capability and valuation - on the provision public goods when
      punishment is possible or not. We find that compared to homogeneous groups,
      asymmetric valuations for the public good have negative effects on cooperation
      and its enforcement through informal sanctions. Asymmetric capabilities in
      providing the public good, in contrast, have a positive and stabilizing effect on
      voluntary contributions. The main reason for these results are the different
      externalities contributions have on the other group members' payoffs affecting
      individuals' willingness to cooperate. We thus provide evidence that it is not
      the asymmetric nature of groups per se that facilitates or impedes collective
      action, but that it is rather the nature of asymmetry that determines the degree
      of cooperation and the level of public good provision.

PMID- 29367795
TI  - Assimilation of SMOS Retrievals in the Land Information System.
AB  - The Soil Moisture and Ocean Salinity (SMOS) satellite provides retrievals of soil
      moisture in the upper 5 cm with a 30-50 km resolution and a mission accuracy
      requirement of 0.04 cm3 cm-3. These observations can be used to improve land
      surface model soil moisture states through data assimilation. In this paper, SMOS
      soil moisture retrievals are assimilated into the Noah land surface model via an
      Ensemble Kalman Filter within the NASA Land Information System. Bias correction
      is implemented using Cumulative Distribution Function (CDF) matching, with points
      aggregated by either land cover or soil type to reduce sampling error in
      generating the CDFs. An experiment was run for the warm season of 2011 to test
      SMOS data assimilation and to compare assimilation methods. Verification of soil
      moisture analyses in the 0-10 cm upper layer and root zone (0-1 m) was conducted
      using in situ measurements from several observing networks in the central and
      southeastern United States. This experiment showed that SMOS data assimilation
      significantly increased the anomaly correlation of Noah soil moisture with
      station measurements from 0.45 to 0.57 in the 0-10 cm layer. Time series at
      specific stations demonstrate the ability of SMOS DA to increase the dynamic
      range of soil moisture in a manner consistent with station measurements. Among
      the bias correction methods, the correction based on soil type performed best at
      bias reduction but also reduced correlations. The vegetation-based correction did
      not produce any significant differences compared to using a simple uniform
      correction curve.

PMID- 29367796
TI  - Nonlinear Functional Connectivity Network Recovery in the Human Brain with Mutual
      Connectivity Analysis (MCA): Convergent Cross-Mapping and Non-Metric Clustering.
AB  - We explore a computational framework for functional connectivity analysis in
      resting-state functional MRI (fMRI) data acquired from the human brain for
      recovering the underlying network structure and understanding causality between
      network components. Termed mutual connectivity analysis (MCA), this framework
      involves two steps, the first of which is to evaluate the pair-wise cross
      prediction performance between fMRI pixel time series within the brain. In a
      second step, the underlying network structure is subsequently recovered from the
      affinity matrix using non-metric network clustering approaches, such as the so
      called Louvain method. Finally, we use convergent cross-mapping (CCM) to study
      causality between different network components. We demonstrate our MCA framework
      in the problem of recovering the motor cortex network associated with hand
      movement from resting state fMRI data. Results are compared with a ground truth
      of active motor cortex regions as identified by a task-based fMRI sequence
      involving a finger-tapping stimulation experiment. Our results regarding
      causation between regions of the motor cortex revealed a significant directional
      variability and were not readily interpretable in a consistent manner across
      subjects. However, our results on whole-slice fMRI analysis demonstrate that MCA
      based model-free recovery of regions associated with the primary motor cortex and
      supplementary motor area are in close agreement with localization of similar
      regions achieved with a task-based fMRI acquisition. Thus, we conclude that our
      MCA methodology can extract and visualize valuable information concerning the
      underlying network structure between different regions of the brain in resting
      state fMRI.

PMID- 29367793
TI  - Phylogenetic classification and generic delineation of Calyptosphaeria gen. nov.,
      Lentomitella, Spadicoides and Torrentispora (Sordariomycetes).
AB  - The genus Ceratostomella has a long history of taxonomic confusion. While species
      with evanescent asci have been transferred to the Microascales and
      Ophiostomatales, the taxonomic status of species with persistent asci has not
      been completely resolved. In previous studies using DNA sequence data, cultures
      and morphology, several Ceratostomella spp. were allocated in 13 genera in the
      Eurotiomycetes and Sordariomycetes. In our study, the systematics of the
      remaining Ceratostomella spp. with persistent asci is revisited with new
      collection data, cultures and phylogeny based on novel DNA sequences from six
      nuclear loci. Bayesian inference and Maximum Likelihood analyses support the
      monophyly of several wood-inhabiting species formerly classified in
      Ceratostomella and other unknown morphologically similar taxa and their division
      into four genera, i.e. Lentomitella, Spadicoides, Torrentispora and the newly
      described Calyptosphaeria. This robust clade represents the order
      Xenospadicoidales in the Sordariomycetidae. Comparative analysis of the ITS2
      secondary structure revealed a genetic variation among Lentomitella isolates; 11
      species were recognised, of which five are newly introduced and two are new
      combinations. Other taxonomic novelties include four new species and eight new
      combinations in Calyptosphaeria, Spadicoides, and Torrentispora. Molecular data
      suggest that Spadicoides is polyphyletic. The core of the genus is positioned in
      the Xenospadicoidales; Spadicoides s. str. is experimentally linked with sexual
      morphs for the first time. Based on DNA sequence data, the monotypic genera
      Xenospadicoides and Pseudodiplococcium are reduced to synonymy under Spadicoides,
      while Fusoidispora and Pseudoannulatascus are synonymised with Torrentispora.
      Members of the Xenospadicoidales inhabit decaying wood in terrestrial and
      freshwater environments and share a few morphological characters such as the
      absence of stromatic tissue, ascomata with a cylindrical or rostrate neck,
      similar anatomies of the ascomatal walls, thin-walled unitunicate asci with a non
      amyloid apical annulus, disintegrating paraphyses, usually ellipsoidal to
      fusiform ascospores and holoblastic-denticulate or tretic conidiogenesis. Revised
      Ceratostomella spp. with persistent asci are listed and the taxonomic status of
      each species is re-evaluated based on revision of the holotype and other
      representative material, published details and available phylogenetic data.

PMID- 29367797
TI  - Assessing vertebral fracture risk on volumetric quantitative computed tomography
      by geometric characterization of trabecular bone structure.
AB  - The current clinical standard for measuring Bone Mineral Density (BMD) is dual X
      ray absorptiometry, however more recently BMD derived from volumetric
      quantitative computed tomography has been shown to demonstrate a high association
      with spinal fracture susceptibility. In this study, we propose a method of
      fracture risk assessment using structural properties of trabecular bone in spinal
      vertebrae. Experimental data was acquired via axial multi-detector CT (MDCT) from
      12 spinal vertebrae specimens using a whole-body 256-row CT scanner with a
      dedicated calibration phantom. Common image processing methods were used to
      annotate the trabecular compartment in the vertebral slices creating a circular
      region of interest (ROI) that excluded cortical bone for each slice. The pixels
      inside the ROI were converted to values indicative of BMD. High dimensional
      geometrical features were derived using the scaling index method (SIM) at
      different radii and scaling factors (SF). The mean BMD values within the ROI were
      then extracted and used in conjunction with a support vector machine to predict
      the failure load of the specimens. Prediction performance was measured using the
      root-mean-square error (RMSE) metric and determined that SIM combined with mean
      BMD features (RMSE = 0.82 +/- 0.37) outperformed MDCT-measured mean BMD (RMSE =
      1.11 +/- 0.33) (p < 10-4). These results demonstrate that biomechanical strength
      prediction in vertebrae can be significantly improved through the use of SIM
      derived texture features from trabecular bone.

PMID- 29367798
TI  - NEURAL RESPONSES TO APPEARANCE-BEHAVIOR CONGRUITY.
AB  - Research evidences stronger reactions toward those whose behaviors seem
      consistent with appearance. To better understand the processes underlying
      appearance-behavior congruity effects, we assessed regions responding as a
      function of the congruity between visual (appearance) and abstract (behavior)
      cues. Using fMRI, trustworthy- and untrustworthy-looking faces were paired with
      positive, negative, or neutral behaviors. Approach judgments were stronger for
      congruent over incongruent targets, replicating prior work. Incongruent targets
      (e.g., untrustworthy face/positive behavior) elicited medial prefrontal (mPFC)
      and dorsolateral prefrontal (dlPFC) cortex activity more than congruent (e.g.,
      untrustworthy face/negative behavior), suggesting processing incongruent targets
      requires additional mentalizing and controlled processing. Individual differences
      in enjoying interpersonal interactions negatively correlated with mPFC activity
      toward incongruent over congruent targets, suggesting more effortful processing
      of incongruent targets for individuals with lower levels of social motivation.
      These findings indicate mPFC contributions to processing incongruent appearance
      behavior cues, but suggest that individual differences may temper the extent of
      this effect.

PMID- 29367799
TI  - Do Gender Differences in Perceived Prototypical Computer Scientists and Engineers
      Contribute to Gender Gaps in Computer Science and Engineering?
AB  - Women are vastly underrepresented in the fields of computer science and
      engineering (CS&E). We examined whether women might view the intellectual
      characteristics of prototypical individuals in CS&E in more stereotype-consistent
      ways than men might and, consequently, show less interest in CS&E. We asked 269
      U.S. college students (187, 69.5% women) to describe the prototypical computer
      scientist (Study 1) or engineer (Study 2) through open-ended descriptions as well
      as through a set of trait ratings. Participants also rated themselves on the same
      set of traits and rated their similarity to the prototype. Finally, participants
      in both studies were asked to describe their likelihood of pursuing future
      college courses and careers in computer science (Study 1) or engineering (Study
      2). Across both studies, we found that women offered more stereotype-consistent
      ratings than did men of the intellectual characteristics of prototypes in CS
      (Study 1) and engineering (Study 2). Women also perceived themselves as less
      similar to the prototype than men did. Further, the observed gender differences
      in prototype perceptions mediated the tendency for women to report lower interest
      in CS&E fields relative to men. Our work highlights the importance of prototype
      perceptions for understanding the gender gap in CS&E and suggests avenues for
      interventions that may increase women's representation in these vital fields.

PMID- 29367800
TI  - The long-term studies of osmotic membrane distillation.
AB  - The results of osmotic membrane distillation carried out for 2.5 years were
      presented in this work. The influence of the process conditions, such as
      temperature and brine concentration on the permeate flux, was investigated. The
      saturated NaCl solutions and distilled water were used as a stripping solution
      and feed, respectively. A continuous regeneration of stripping solution was
      conducted using a method of natural evaporation from the surface of Bialecki
      rings to the air surrounding the installation. The possibilities of application
      of Accurel PP S6/2 hydrophobic polypropylene membranes were tested. It was
      studied whether a saturation stripping solution does not cause scaling and
      wettability of membranes. It was found that most of the pores in the used
      membranes were non-wetted, and the salt retention over 99% was maintained during
      a study period. However, the obtained permeate flux was decreased by 10-20%. The
      SEM examinations revealed that it was caused by amorphous deposit, which was
      formed on the membrane surface on the brine side. The SEM-EDS analysis
      demonstrated that the deposit composition mainly included Si and O.

PMID- 29367801
TI  - Spectroelectrochemistry of poly(3-hexylthiophenes) in solution.
AB  - Abstract: The first comprehensive spectroelectrochemical account of the behaviour
      of regioregular (RR-P3HT) and statistical (ST-P3HT) poly(3-hexylthiophenes) in
      solution is presented, in contrast to the many reports dealing with P3HT films
      merely deposited from solution. The conducted experiments revealed that the two
      types of P3HTs behave in sharply different ways upon the application of
      electrochemical stimuli: ST-P3HT readily precipitates at mildly oxidative
      potentials, while the precipitation of the RR-P3HT takes place to a much lesser
      extent, even at higher potentials. The two polymers, studied via UV-Vis-NIR-EPR
      spectroelectrochemistry, exhibited properties mostly in line with earlier
      reports. Further study revealed that RR-P3HT largely remains in solution, even in
      its doped form, whereas only traces of the doped ST-P3HT are observed in solution
      in identical conditions. The high concentration of the doped RR-P3HT in solution
      can be explained by its ability to form soluble polymer agglomerates, in which
      the positive charge of the p-doped chains is stabilised by and delocalised over
      neighbouring, interacting undoped chains. These conclusions are consistent with
      SEM micrographs, which show that after cycling the potential of the electrode in
      a solution of ST-P3HT, a uniform layer is formed, covering most of the surface of
      the electrode, whereas in the case of RR-P3HT surface coverage is marginal and
      formed layer has the appearance of veined blotches. Graphical abstract: 

PMID- 29367802
TI  - Experimental restoration of coppice-with-standards: Response of understorey
      vegetation from the conservation perspective.
AB  - A substantial part of European lowland woodlands was managed as coppices or wood
      pastures for millennia. However, traditional management forms were almost
      completely abandoned in Central Europe by the middle of the 20th century.
      Combined with the effects of nitrogen deposition and herbivore pressure, shifts
      in management resulted in biodiversity loss affecting particularly light
      demanding oligotrophic plant species. Experimental thinning was applied in a
      former oak coppice-with-standards in an attempt to restore vanishing understorey
      plant communities. Two levels of thinning intensity and zero management as
      control were used on 90 plots. Ten years after the treatment, significant changes
      in species composition and diversity were observed in heavily thinned plots,
      while moderate thinning had mostly insignificant effects. Light-demanding
      oligotrophic species significantly increased, indicating positive consequences of
      restoration. However, heavy thinning also brought about the expansion of native
      ruderal species. Alien species remained unchanged. We conclude that the
      restoration of coppice-with-standards can be an efficient tool to support
      vanishing light-demanding woodland species. Combined with biodiversity benefits,
      the increasing demand for biofuel may contribute to the renaissance of
      traditional management forms in forestry.

PMID- 29367803
TI  - Regulation of Floral Terpenoid Emission and Biosynthesis in Sweet Basil (Ocimum
      basilicum).
AB  - Past studies have focused on the composition of essential oil of Ocimum basilicum
      leaves, but data on composition and regulation of its aerial emissions,
      especially floral volatile emissions are scarce. We studied the chemical profile,
      within-flower spatial distribution (sepals, petals, pistils with stamina and
      pedicels), diurnal emission kinetics and effects of exogenous methyl jasmonate
      (MeJA) application on the emission of floral volatiles by dynamic headspace
      collection and identification using gas chromatography-mass spectrometry (GC-MS)
      and proton transfer reaction mass spectrometry (PTR-MS). We observed more
      abundant floral emissions from flowers compared with leaves. Sepals were the main
      emitters of floral volatiles among the flower parts studied. The emissions of
      lipoxygenase compounds (LOX) and monoterpenoids, but not sesquiterpene emissions,
      displayed a diurnal variation driven by light. Response to exogenous MeJA
      treatment of flowers consisted of a rapid stress response and a longer-term
      acclimation response. The initial response was associated with enhanced emissions
      of fatty acid derivatives, monoterpenoids, and sesquiterpenoids without variation
      of the composition of individual compounds. The longer-term response was
      associated with enhanced monoterpenoid and sesquiterpenoid emissions with
      profound changes in the emission spectrum. According to correlated patterns of
      terpenoid emission changes upon stress, highlighted by a hierarchical cluster
      analysis, candidate terpenoid synthases responsible for observed diversity and
      complexity of released terpenoid blends were postulated. We conclude that flower
      volatile emissions differ quantitatively and qualitatively from leaf emissions,
      and overall contribute importantly to O. basilicum flavor, especially under
      stress conditions.

PMID- 29367804
TI  - Understanding How Domestic Violence Support Services Promote Survivor Well-being:
      A Conceptual Model.
AB  - Domestic violence (DV) victim service programs have been increasingly expected by
      legislators and funders to demonstrate that they are making a significant
      difference in the lives of those using their services. Alongside this
      expectation, they are being asked to describe the Theory of Change guiding how
      they believe their practices lead to positive results for survivors and their
      children. Having a widely accepted conceptual model is not just potentially
      useful to funders and policy makers as they help shape policy and practice -- it
      can also help programs continually reflect upon and improve their work. This
      paper describes the iterative and collaborative process undertaken to generate a
      conceptual model describing how DV victim services are expected to improve
      survivors' lives. The Social and Emotional Well-Being Framework guiding the model
      is an ideal structure to use to describe the goals and practices of DV programs
      because this framework: (1) accurately represents DV programs' goal of helping
      survivors and their children thrive; and (2) recognizes the importance of
      community, social, and societal context in influencing individuals' social and
      emotional well-being. The model was designed to guide practice and to generate
      new questions for research and evaluation that address individual, community, and
      systems factors that promote or hinder survivor safety and well-being.

PMID- 29367805
TI  - "Give me some space": exploring youth to parent aggression and violence.
AB  - A small scale qualitative project, undertaken by an interdisciplinary domestic
      violence research group involving academic researchers and research assistants,
      with colleagues from Independent Domestic Abuse Services (IDAS), investigated
      youth aggression and violence against parents. Following the literature review,
      data was generated through several research conversations with young people (n =
      2), through semi-structured interviews with mothers (n = 3) and practitioners (n
      = 5), and through a practitioner focus group (n = 8). Thematic analysis and
      triangulation of the data from parents, practitioners and young people, elicited
      interconnected and complex overarching themes. Young people could be both victim
      and perpetrator. The witnessing or experiencing of domestic aggression and
      violence raised the concept of 'bystander children'. The impact of young people
      experiencing familial violence was underestimated by parents. For practitioners,
      the effects of working with domestic violence was shown to be significant - both
      positively and negatively.

PMID- 29367806
TI  - Morpho-phonemic analysis boosts word reading for adult struggling readers.
AB  - A randomized control trial compared the effects of two kinds of vocabulary
      instruction on component reading skills of adult struggling readers. Participants
      seeking alternative high school diplomas received 8 h of scripted tutoring to
      learn forty academic vocabulary words embedded within a civics curriculum. They
      were matched for language background and reading levels, then randomly assigned
      to either morpho-phonemic analysis teaching word origins, morpheme and syllable
      structures, or traditional whole word study teaching multiple sentence contexts,
      meaningful connections, and spellings. Both groups made comparable gains in
      learning the target words, but the morpho-phonemic group showed greater gains in
      reading unfamiliar words on standardized tests of word reading, including word
      attack and word recognition. Findings support theories of word learning and
      literacy that promote explicit instruction in word analysis to increase poor
      readers' linguistic awareness by revealing connections between morphological,
      phonological, and orthographic structures within words.

PMID- 29367807
TI  - Rhythm production at school entry as a predictor of poor reading and spelling at
      the end of first grade.
AB  - Rhythm plays an organisational role in the prosody and phonology of language, and
      children with literacy difficulties have been found to demonstrate poor rhythmic
      perception. This study explored whether students' performance on a simple rhythm
      task at school entry could serve as a predictor of whether they would face
      difficulties in word reading and spelling at the end of grade 1. The participants
      were 479 Norwegian 6-year-old first graders randomized as controls in the
      longitudinal RCT on track (n = 1171). Rhythmic timing and pre-reading skills were
      tested individually at school entry on a digital tablet. On the rhythm task, the
      students were told to tap a drum appearing on the screen to two different rhythms
      (2 Hz paced and 1.5 Hz paced). Children's responses were recorded as they tapped
      on the screen with their index finger. Significant group differences were found
      in rhythm tapping ability measured at school entry, when groups were defined upon
      whether children went on to score above or below the 20th percentile reading and
      spelling thresholds in national assessment tests at the end of grade one.
      Inclusion of the school-entry rhythmic tapping measure into a model of
      classification accuracy for above or below threshold reading and spelling
      improved accuracy of classification by 6.2 and 9.2% respectively.

PMID- 29367808
TI  - Spin-label Order Parameter Calibrations for Slow Motion.
AB  - Calibrations are given to extract orientation order parameters from pseudo-powder
      electron paramagnetic resonance line shapes of 14N-nitroxide spin labels
      undergoing slow rotational diffusion. The nitroxide z-axis is assumed parallel to
      the long molecular axis. Stochastic-Liouville simulations of slow-motion 9.4-GHz
      spectra for molecular ordering with a Maier-Saupe orientation potential reveal a
      linear dependence of the splittings, [Formula: see text] and [Formula: see text],
      of the outer and inner peaks on order parameter [Formula: see text] that depends
      on the diffusion coefficient [Formula: see text] which characterizes fluctuations
      of the long molecular axis. This results in empirical expressions for order
      parameter and isotropic hyperfine coupling: [Formula: see text] and [Formula: see
      text], respectively. Values of the calibration constants [Formula: see text],
      [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see
      text] are given for different values of [Formula: see text] in fast and slow
      motional regimes. The calibrations are relatively insensitive to anisotropy of
      rotational diffusion [Formula: see text], and corrections are less significant
      for the isotropic hyperfine coupling than for the order parameter.

PMID- 29367809
TI  - Noise and Dissipation on Coadjoint Orbits.
AB  - We derive and study stochastic dissipative dynamics on coadjoint orbits by
      incorporating noise and dissipation into mechanical systems arising from the
      theory of reduction by symmetry, including a semidirect product extension. Random
      attractors are found for this general class of systems when the Lie algebra is
      semi-simple, provided the top Lyapunov exponent is positive. We study in details
      two canonical examples, the free rigid body and the heavy top, whose stochastic
      integrable reductions are found and numerical simulations of their random
      attractors are shown.

PMID- 29367810
TI  - Particle Interactions Mediated by Dynamical Networks: Assessment of Macroscopic
      Descriptions.
AB  - We provide a numerical study of the macroscopic model of Barre et al. (Multiscale
      Model Simul, 2017, to appear) derived from an agent-based model for a system of
      particles interacting through a dynamical network of links. Assuming that the
      network remodeling process is very fast, the macroscopic model takes the form of
      a single aggregation-diffusion equation for the density of particles. The
      theoretical study of the macroscopic model gives precise criteria for the phase
      transitions of the steady states, and in the one-dimensional case, we show
      numerically that the stationary solutions of the microscopic model undergo the
      same phase transitions and bifurcation types as the macroscopic model. In the two
      dimensional case, we show that the numerical simulations of the macroscopic model
      are in excellent agreement with the predicted theoretical values. This study
      provides a partial validation of the formal derivation of the macroscopic model
      from a microscopic formulation and shows that the former is a consistent
      approximation of an underlying particle dynamics, making it a powerful tool for
      the modeling of dynamical networks at a large scale.

PMID- 29367811
TI  - On the Quasistatic Limit of Dynamic Evolutions for a Peeling Test in Dimension
      One.
AB  - The aim of this paper is to study the quasistatic limit of a one-dimensional
      model of dynamic debonding. We start from a dynamic problem that strongly couples
      the wave equation in a time-dependent domain with Griffith's criterion for the
      evolution of the domain. Passing to the limit as inertia tends to zero, we find
      that the limit evolution satisfies a stability condition; however, the activation
      rule in Griffith's (quasistatic) criterion does not hold in general, thus the
      limit evolution is not rate-independent.

PMID- 29367813
TI  - New half-discrete Hilbert inequalities for three variables.
AB  - In this paper, we obtain two new half-discrete Hilbert inequalities for three
      variables. The obtained inequalities are with the best constant factor. Moreover,
      we give their equivalent forms.

PMID- 29367814
TI  - Convergence analysis of modulus-based matrix splitting iterative methods for
      implicit complementarity problems.
AB  - In this paper, we demonstrate a complete version of the convergence theory of the
      modulus-based matrix splitting iteration methods for solving a class of implicit
      complementarity problems proposed by Hong and Li (Numer. Linear Algebra Appl.
      23:629-641, 2016). New convergence conditions are presented when the system
      matrix is a positive-definite matrix and an [Formula: see text]-matrix,
      respectively.

PMID- 29367812
TI  - Estrogen receptor subtype ratio change protects against podocyte damage.
AB  - Women are relatively protected against the development and progression of
      glomerulosclerosis (GS) prior to menopause. However, the "female advantage" is
      lost in women who are either diabetic, post-menopausal or both. We showed that
      17beta-estradiol (E2) was effective in prevention of diabetic GS development in
      part through the stabilization of podocyte cytoskeleton and a change in estrogen
      receptor (ER) subtype ratio. The objective of this study was to examine whether
      resveratrol (RSV), reported to have estrogen-like action and renoprotective
      activity against diabetic GS, would affect similar pathways. After in vitro
      treatment with RSV we found a change in the ERalpha and ERbeta expression ratio
      in favor of ERbeta, suppression of heat shock protein 25 (Hsp25) expression and
      increase in beta1-integrin expression, important for maintaining podocyte
      cytoskeleton. We noted a reduction of insulin-like growth factor 1 receptor
      (IGFR1) expression, decrease in extracellular signal-regulated kinase (ERK)
      activation, decrease in reactive oxygen species (ROS), and decrease in cleaved
      caspase 3 expression. We found an increase in [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] (MTT) and an increase in matrix metalloproteinases
      (MMP-2 and MMP-9) activity. Using cre-loxP strategy we developed podocyte
      specific ERalpha knockout mice to show the importance of ERbeta. In isolated
      podocytes, we confirmed reduction of ERalpha expression in conjunction with a
      decrease in IGFR1 expression, ERK and increase of MMP-2 similar to that of our in
      vitro treatment with RSV. Taken together these data suggest an important role for
      ERbeta and ER subtype ratio in podocyte stabilization. Therefore RSV or other
      regulators of ER pathways could offer protection against diabetic and age-related
      podocyte changes.

PMID- 29367815
TI  - On Pell, Pell-Lucas, and balancing numbers.
AB  - In this paper, we derive some identities on Pell, Pell-Lucas, and balancing
      numbers and the relationships between them. We also deduce some formulas on the
      sums, divisibility properties, perfect squares, Pythagorean triples involving
      these numbers. Moreover, we obtain the set of positive integer solutions of some
      specific Pell equations in terms of the integer sequences mentioned in the text.

PMID- 29367816
TI  - Simultaneous and semi-alternating projection algorithms for solving split
      equality problems.
AB  - In this article, we first introduce two simultaneous projection algorithms for
      solving the split equality problem by using a new choice of the stepsize, and
      then propose two semi-alternating projection algorithms. The weak convergence of
      the proposed algorithms is analyzed under standard conditions. As applications,
      we extend the results to solve the split feasibility problem. Finally, a
      numerical example is presented to illustrate the efficiency and advantage of the
      proposed algorithms.

PMID- 29367817
TI  - Some inequalities on the spectral radius of matrices.
AB  - Let [Formula: see text] be nonnegative matrices. In this paper, some upper bounds
      for the spectral radius [Formula: see text] are proposed. These bounds generalize
      some existing results, and comparisons between these bounds are also considered.

PMID- 29367819
TI  - The uniqueness of a nonlinear diffusion equation related to the p-Laplacian.
AB  - Consider a nonlinear diffusion equation related to the p-Laplacian. Different
      from the usual evolutionary p-Laplacian equation, the equation is degenerate on
      the boundary due to the fact that the diffusion coefficient is dependent on the
      distance function. Not only the existence of the weak solution is established,
      but also the uniqueness of the weak solution is proved.

PMID- 29367818
TI  - Some weighted inequalities for Hausdorff operators and commutators.
AB  - In this paper, we consider the problem of boundedness of Hausdorff operator on
      weighted central Morrey spaces. In particular, we obtain sharp bounds for
      Hausdorff operators on power weighted central Morrey spaces. Analogous results
      for the commutators of Hausdorff operators when the symbol functions belong to
      weighted central-BMO spaces are obtained as well.

PMID- 29367820
TI  - Schur convexity of the generalized geometric Bonferroni mean and the relevant
      inequalities.
AB  - In this paper, we discuss the Schur convexity, Schur geometric convexity and
      Schur harmonic convexity of the generalized geometric Bonferroni mean. Some
      inequalities related to the generalized geometric Bonferroni mean are established
      to illustrate the applications of the obtained results.

PMID- 29367821
TI  - On almost B-summable double sequence spaces.
AB  - The concept of a four-dimensional generalized difference matrix and its domain on
      some double sequence spaces was recently introduced and studied by Tug and Basar
      (AIP Conference Proceedings, vol. 1759, 2016) and Tug (J. Inequal. Appl.
      2017(1):149, 2017). In this present paper, as a natural continuation of (J.
      Inequal. Appl. 2017(1):149, 2017), we introduce new almost null and almost
      convergent double sequence spaces [Formula: see text] and [Formula: see text] as
      the four-dimensional generalized difference matrix [Formula: see text] domain in
      the spaces [Formula: see text] and [Formula: see text], respectively. Firstly, we
      prove that the spaces [Formula: see text] and [Formula: see text] of double
      sequences are Banach spaces under some certain conditions. Then we give an
      inclusion relation of these new almost convergent double sequence spaces.
      Moreover, we identify the alpha-dual, [Formula: see text]-dual and gamma-dual of
      the space [Formula: see text]. Finally, we characterize some new matrix classes
      [Formula: see text], [Formula: see text], and we complete this work with some
      significant results.

PMID- 29367822
TI  - Berry-Esseen bounds of weighted kernel estimator for a nonparametric regression
      model based on linear process errors under a LNQD sequence.
AB  - In this paper, the authors investigate the Berry-Esseen bounds of weighted kernel
      estimator for a nonparametric regression model based on linear process errors
      under a LNQD random variable sequence. The rate of the normal approximation is
      shown as [Formula: see text] under some appropriate conditions. The results
      obtained in the article generalize or improve the corresponding ones for mixing
      dependent sequences in some sense.

PMID- 29367823
TI  - The law of the iterated logarithm for LNQD sequences.
AB  - Let [Formula: see text] be a stationary LNQD sequence of random variables with
      zero means and finite variance. In this paper, by the Kolmogorov type maximal
      inequality and Stein's method, we establish the result of the law of the iterated
      logarithm for LNQD sequence with less restriction of moment conditions. We also
      prove the law of the iterated logarithm for a linear process generated by an LNQD
      sequence with the coefficients satisfying [Formula: see text] by a Beveridge and
      Nelson decomposition.

PMID- 29367824
TI  - Proximal iteratively reweighted algorithm for low-rank matrix recovery.
AB  - This paper proposes a proximal iteratively reweighted algorithm to recover a low
      rank matrix based on the weighted fixed point method. The weighted singular value
      thresholding problem gains a closed form solution because of the special
      properties of nonconvex surrogate functions. Besides, this study also has shown
      that the proximal iteratively reweighted algorithm lessens the objective function
      value monotonically, and any limit point is a stationary point theoretically.

PMID- 29367825
TI  - Gap functions for quasi-variational inequalities via duality.
AB  - This paper deals with an application of duality theory in optimization to the
      construction of gap functions for quasi-variational inequalities. The same
      approach was investigated for variational inequalities and equilibrium problems
      in (Pac. J. Optim. 2(3): 667-678, 2006; Asia-Pac. J. Oper. Res. 24(3): 353-371,
      2007), and the study shows that we can obtain some previous results for
      variational inequalities as special cases. Moreover, some applications dealing
      with the generalized Nash equilibrium problems and mixed variational inequalities
      are presented.

PMID- 29367826
TI  - The spectral norms of geometric circulant matrices with the generalized k-Horadam
      numbers.
AB  - In this paper, we use the algebra methods, the properties of the r-circulant
      matrix and the geometric circulant matrix to study the upper and lower bound
      estimate problems for the spectral norms of a geometric circulant matrix
      involving the generalized k-Horadam numbers, and we obtain some sharp estimations
      for them. We can also give a new estimation for the norms of a r-circulant matrix
      involving the generalized k-Horadam numbers.

PMID- 29367827
TI  - Weighted almost convergence and related infinite matrices.
AB  - The purpose of this paper is to introduce the notion of weighted almost
      convergence of a sequence and prove that this sequence endowed with the sup-norm
      [Formula: see text] is a BK-space. We also define the notions of weighted almost
      conservative and regular matrices and obtain necessary and sufficient conditions
      for these matrix classes. Moreover, we define a weighted almost A-summable
      sequence and prove the related interesting result.

PMID- 29367828
TI  - Analysis of propeller-induced ground vortices by particle image velocimetry.
AB  - Abstract: The interaction between a propeller and its self-induced vortices
      originating on the ground is investigated in a scaled experiment. The velocity
      distribution in the flow field in two different planes containing the self
      induced vortices is measured by particle image velocimetry (PIV). These planes
      are a wall-parallel plane in close proximity to the ground and a wall-normal
      plane just upstream of the propeller. Based on the visualization of the flow
      field in these two planes, the occurrence of ground vortices and its domain
      boundary are analysed. The elevation of the propeller from the ground and the
      thrust of the propeller are two parameters that determine the occurrence of
      ground vortices. The main features of the propeller inflow in the presence of the
      ground vortices are highlighted. Moreover, the analysis of the non-uniform inflow
      in the azimuthal direction shows that with increasing the propeller thrust
      coefficient and decreasing the elevation of the propeller above the ground, the
      variation of the inflow angle of the blade increases. Graphical Abstract: 

PMID- 29367829
TI  - Numerical analysis of propeller induced ground vortices by actuator disk model.
AB  - Abstract: During the ground operation of aircraft, the interaction between the
      propulsor-induced flow field and the ground may lead to the generation of ground
      vortices. Utilizing numerical approaches, the source of vorticity entering ground
      vortices is investigated. The results show that the production of wall-parallel
      components of vorticity has a strong contribution from the wall-parallel
      components of the pressure gradient on the wall, which is generated by the action
      of the propulsor. This mechanism is a supplementation for the vorticity
      transported from the far-field boundary layer, which has been assumed the main
      vorticity source in a number of previous publications. Furthermore, the
      quantitative prediction of the occurrence of ground vortices is performed from
      the numerical results. As the distance of the propeller form the ground
      decreases, and as the thrust of the propeller increases, ground vortices are
      generated from the ground and enter the propeller. In addition, the vortices
      which exist near the ground but does not enter the propeller plane are observed
      and visualized by three-dimensional data. Graphical abstract: 

PMID- 29367830
TI  - Numerical simulations of magnetic resonance elastography using finite element
      analysis with a linear heterogeneous viscoelastic model.
AB  - Abstract: Magnetic resonance elastography (MRE) is a technique to identify the
      viscoelastic moduli of biological tissues by solving the inverse problem from the
      displacement field of viscoelastic wave propagation in a tissue measured by MRI.
      Because finite element analysis (FEA) of MRE evaluates not only the viscoelastic
      model for a tissue but also the efficiency of the inversion algorithm, we
      developed FEA for MRE using commercial software called ANSYS, the Zener model for
      displacement field of a wave inside tissue, and an inversion algorithm called the
      modified integral method. The profile of the simulated displacement field by FEA
      agrees well with the experimental data measured by MRE for gel phantoms.
      Similarly, the value of storage modulus (i.e., stiffness) recovered using the
      modified integral method with the simulation data is consistent with the value
      given in FEA. Furthermore, applying the suggested FEA to a human liver
      demonstrates the effectiveness of the present simulation scheme. Graphical
      abstract: 

PMID- 29367831
TI  - Experimental and numerical study of heat transfer through a synchronous belt
      transmission type AT10.
AB  - In most industrial applications, the re-use of belts in power transmissions
      continues to increase and invade the market especially in automobiles where
      various types of belts are used. For this purpose, the belt manufacturers are
      aware of the importance and the valuable advantages of this transmission member
      and put all their efforts to develop and improve its geometrical and mechanical
      characteristics in order to achieve an optimal service life. Indeed, this article
      is devoted to an experimental and numerical thermal study of a toothed belt
      transmission type AT10. The tests were carried out on an original derrick of test
      for the purpose of measuring belt and pulley temperatures, detector devices and
      data acquisitions will also be described. Further, we have developed a model that
      calculates the heat flux through our pulley-belt transmission. The results will
      be synthesized to make a comparison between two thermal fluxes. The first is
      determined from our mathematical model and the second is calculated using the
      thermal simulation of this belt pulley transmission. Finally, a discussion of the
      results, which will allow us to fully understand this thermal phenomenon.

PMID- 29367832
TI  - Resistive states in strontium titanate thin films: Bias effects and mechanisms at
      high and low temperature.
AB  - A study on charge transport properties of thin film Fe-doped SrTiO3 epitaxially
      grown on Nb-doped SrTiO3 is reported. Electric measurements between 350  degrees
      C and 750  degrees C show a transition from predominant ionic to electronic
      conduction and lower conductivity of the thin films compared to the bulk of
      polycrystalline samples. Defect chemical changes at elevated temperature were
      investigated by applying a bias voltage. A model is described which successfully
      predicts additional features such as inductive loops or extra semicircles
      measureable by impedance spectroscopy as well as the complicated time dependence
      of electric DC-measurements. With this model it is also possible to calculate the
      negligibly small ionic conductivity next to the dominating electronic
      conductivity in the high temperature regime. The ionic conductivity is referenced
      by oxygen isotope depth profiling. Changes of resistive states in Fe-doped SrTiO3
      thin films at high temperature and moderate fields are compared to room
      temperature resistive switching phenomena at high electric fields. A conductive
      filament based switching process is observed at room temperature, and the
      capability for forming such filaments and their electric properties is further
      analysed using microelectrodes.

PMID- 29367833
TI  - Forecast and analysis of the cosmological redshift drift.
AB  - The cosmological redshift drift could lead to the next step in high-precision
      cosmic geometric observations, becoming a direct and irrefutable test for cosmic
      acceleration. In order to test the viability and possible properties of this
      effect, also called Sandage-Loeb (SL) test, we generate a model-independent mock
      data set in order to compare its constraining power with that of the future mock
      data sets of Type Ia Supernovae (SNe) and Baryon Acoustic Oscillations (BAO). The
      performance of those data sets is analyzed by testing several cosmological models
      with the Markov chain Monte Carlo (MCMC) method, both independently as well as
      combining all data sets. Final results show that, in general, SL data sets allow
      for remarkable constraints on the matter density parameter today [Formula: see
      text] on every tested model, showing also a great complementarity with SNe and
      BAO data regarding dark energy parameters.

PMID- 29367835
TI  - Effects of bedtime periocular and posterior cervical cutaneous warming on sleep
      status in adult male subjects: a preliminary study.
AB  - Appropriate warming of the periocular or posterior cervical skin has been
      reported to induce autonomic or mental relaxation in humans. To clarify the
      effects of cutaneous warming on human sleep, eight male subjects with mild sleep
      difficulties were asked to try three experimental conditions at home, each
      lasting for 5 days, in a cross-over manner: warming of the periocular skin with a
      warming device for 10 min before habitual bedtime, warming of the posterior
      cervical skin with a warming device for 30 min before habitual bedtime, and no
      treatment as a control. The warming device had a heat- and steam-generating sheet
      that allowed warming of the skin to 40  degrees C through a chemical reaction
      with iron. Electroencephalograms (EEGs) were recorded during nocturnal sleep
      using an ambulatory EEG device and subjected to spectral analysis. All the
      participants reported their sleep status using a visual analog scale. We found
      that warming of the periocular or posterior cervical skin significantly improved
      subjective sleep status relative to the control. The EEG delta power density in
      the first 90 min of the sleep episode was significantly increased under both
      warming of the periocular or posterior cervical skin relative to the control.
      These results suggest that warming of appropriate skin regions may have favorable
      effects on subjective and objective sleep quality.

PMID- 29367834
TI  - Physiological and autonomic stress responses after prolonged sleep restriction
      and subsequent recovery sleep in healthy young men.
AB  - Purpose: Sleep restriction is increasingly common and associated with the
      development of health problems. We investigated how the neuroendocrine stress
      systems respond to prolonged sleep restriction and subsequent recovery sleep in
      healthy young men. Methods: After two baseline (BL) nights of 8 h time in bed
      (TIB), TIB was restricted to 4 h per night for five nights (sleep restriction,
      SR, n = 15), followed by three recovery nights (REC) of 8 h TIB, representing a
      busy workweek and a recovery weekend. The control group (n = 8) had 8 h TIB
      throughout the experiment. A variety of autonomic cardiovascular parameters,
      together with salivary neuropeptide Y (NPY) and cortisol levels, were assessed.
      Results: In the control group, none of the parameters changed. In the
      experimental group, heart rate increased from 60 +/- 1.8 beats per minute (bpm)
      at BL, to 63 +/- 1.1 bpm after SR and further to 65 +/- 1.8 bpm after REC. In
      addition, whole day low-frequency to-high frequency (LF/HF) power ratio of heart
      rate variability increased from 4.6 +/- 0.4 at BL to 6.0 +/- 0.6 after SR. Other
      parameters, including salivary NPY and cortisol levels, remained unaffected.
      Conclusions: Increased heart rate and LF/HF power ratio are early signs of an
      increased sympathetic activity after prolonged sleep restriction. To reliably
      interpret the clinical significance of these early signs of physiological stress,
      a follow-up study would be needed to evaluate if the stress responses escalate
      and lead to more unfavourable reactions, such as elevated blood pressure and a
      subsequent elevated risk for cardiovascular health problems.

PMID- 29367836
TI  - Polytolerance to abiotic stresses: how universal is the shade-drought tolerance
      trade-off in woody species?
AB  - Aims: According to traditional ecophysiological theories stress tolerance of
      plants is predominately determined by universal physiochemical constraints. Plant
      acclimation to environmental stress therefore compromises plant performance under
      a different stress, hindering successful toleration of several abiotic stress
      factors simultaneously. Yet, recent studies have shown that these trade-offs are
      less exclusive than postulated so far, leaving more wiggle room for gaining
      polytolerance through adaptations We tested whether the polytolerance to shade
      and drought depends on cold and waterlogging tolerances - hypothesizing that
      polytolerance patterns in different species groups (angiosperms vs. gymnosperms;
      deciduous vs. evergreen; species originating from North America, Europe and East
      Asia) depend on the length of the vegetation period and species's dormancy
      through limiting the duration of favourable growing season. Location: Northern
      hemisphere. Methods: Our study analyzed four main abiotic stress factors - shade,
      drought, cold and waterlogging stress - for 806 Northern hemisphere woody species
      using cross-calibrated tolerance rankings. The importance of trade-offs among
      species ecological potentials was evaluated using the species-specific estimates
      of polytolerance to chosen factors. Results: We found that both cold and
      waterlogging tolerance are negatively related to species' capabilities of
      simultaneously tolerating low light and water conditions. While this pattern was
      different in angiosperms and gymnosperms, species region of origin and leaf type
      had no effect on this relationship. Main conclusions: Our results demonstrate
      that adaptation to different abiotic stress factors in woody plants is highly
      complex. Vegetation period length and dormancy are the key factors explaining why
      woody plants are less capable of tolerating both shade and drought in habitats
      where vegetation period is relatively short and water table high. While dormancy
      enables angiosperms to more successfully face additional stress factors besides
      shade and drought, gymnosperms have lower polytolerance, but are better
      tolerators of shade and drought when other environmental factors are favorable.

PMID- 29367838
TI  - An integrated remote sensing and GIS approach for monitoring areas affected by
      selective logging: A case study in northern Mato Grosso, Brazilian Amazon.
AB  - Forest cover disturbances due to processes such as logging and forest fires are a
      widespread issue especially in the tropics, and have heavily affected forest
      biomass and functioning in the Brazilian Amazon in the past decades. Satellite
      remote sensing has played a key role for assessing logging activities in this
      region; however, there are still remaining challenges regarding the
      quantification and monitoring of these processes affecting forested lands. In
      this study, we propose a new method for monitoring areas affected by selective
      logging in one of the hotspots of Mato Grosso state in the Brazilian Amazon,
      based on a combination of object-based and pixel-based classification approaches
      applied on remote sensing data. Logging intensity and changes over time are
      assessed within grid cells of 300 m * 300 m spatial resolution. Our method
      encompassed three main steps: (1) mapping forest/non-forest areas through an
      object-based classification approach applied to a temporal series of Landsat
      images during the period 2000-2015, (2) mapping yearly logging activities from
      soil fraction images on the same Landsat data series, and (3) integrating
      information from previous steps within a regular grid-cell of 300 m * 300 m in
      order to monitor disturbance intensities over this 15-years period. The overall
      accuracy of the baseline forest/non-forest mask (year 2000) and of the
      undisturbed vs disturbed forest (for selected years) were 93% and 84%
      respectively. Our results indicate that annual forest disturbance rates, mainly
      due to logging activities, were higher than annual deforestation rates during the
      whole period of study. The deforested areas correspond to circa 25% of the areas
      affected by forest disturbances. Deforestation rates were highest from 2001 to
      2005 and then decreased considerably after 2006. In contrast, the annual forest
      disturbance rates show high temporal variability with a slow decrease over the 15
      year period, resulting in a significant increase of the ratio between disturbed
      and deforested areas. Although the majority of the areas, which have been
      affected by selective logging during the period 2000-2014, were not deforested by
      2015, more than 70% of the deforested areas in 2015 had been at least once
      identified as disturbed forest during that period.

PMID- 29367839
TI  - A comparison of sample preparation methods for extracting volatile organic
      compounds (VOCs) from equine faeces using HS-SPME.
AB  - Introduction: Disturbance to the hindgut microbiota can be detrimental to equine
      health. Metabolomics provides a robust approach to studying the functional aspect
      of hindgut microorganisms. Sample preparation is an important step towards
      achieving optimal results in the later stages of analysis. The preparation of
      samples is unique depending on the technique employed and the sample matrix to be
      analysed. Gas chromatography mass spectrometry (GCMS) is one of the most widely
      used platforms for the study of metabolomics and until now an optimised method
      has not been developed for equine faeces. Objectives: To compare a sample
      preparation method for extracting volatile organic compounds (VOCs) from equine
      faeces. Methods: Volatile organic compounds were determined by headspace solid
      phase microextraction gas chromatography mass spectrometry (HS-SPME-GCMS).
      Factors investigated were the mass of equine faeces, type of SPME fibre coating,
      vial volume and storage conditions. Results: The resultant method was unique to
      those developed for other species. Aliquots of 1000 or 2000 mg in 10 ml or 20 ml
      SPME headspace were optimal. From those tested, the extraction of VOCs should
      ideally be performed using a divinylbenzene-carboxen-polydimethysiloxane (DVB-CAR
      PDMS) SPME fibre. Storage of faeces for up to 12 months at - 80  degrees C shared
      a greater percentage of VOCs with a fresh sample than the equivalent stored at -
      20  degrees C. Conclusions: An optimised method for extracting VOCs from equine
      faeces using HS-SPME-GCMS has been developed and will act as a standard to enable
      comparisons between studies. This work has also highlighted storage conditions as
      an important factor to consider in experimental design for faecal metabolomics
      studies.

PMID- 29367837
TI  - Appetite-Related Gut Peptides in Obesity and Binge Eating Disorder.
AB  - The worldwide increase in obesity prevalence is a result of positive energy
      balance, with energy intake exceeding expenditure. The eating behavior in obesity
      ranges from mild passive overconsumption to excessive overeating with loss of
      control observed in binge eating disorder (BED). The signaling systems that
      underlie appetite control in BED are complex and, at this point, not well
      understood. The present review highlights the current knowledge of key components
      of the gut peptide system and examines evidence of defects in signaling that
      differentiate obese binge eaters from obese non-binge eaters. The signaling
      network underlying hunger, satiety, and metabolic status includes leptin and
      insulin from energy stores and cholecystokinin, glucagon-like peptide-1, peptide
      YY(3-36), and ghrelin from the gastrointestinal tract. Of the many
      gastrointestinal peptides, ghrelin is the only established appetite-stimulating
      one, whereas cholecystokinin, glucagon-like peptide-1, and peptide YY(3-36)
      promote satiety. Adipose tissue provides hormonal signals via leptin and insulin
      to the brain about energy stores and likely from adiponectin and resistin. Binge
      eating has been related to a dysfunction in the ghrelin signaling system.
      Moreover, the larger gastric capacity observed in BED may further reduce satiety
      signals and contribute to overeating.

PMID- 29367840
TI  - Fitness costs associated with infections of secondary endosymbionts in the
      cassava whitefly species Bemisia tabaci.
AB  - We investigated the dual effects of bacterial infections and diseased cassava
      plants on the fitness and biology of the Bemisia tabaci infesting cassava in
      Africa. Isofemale B. tabaci colonies of sub-Saharan Africa 1-subgroup 3 (SSA1
      SG3), infected with two secondary endosymbiotic bacteria Arsenophonus and
      Rickettsia (AR+) and those free of AR infections (AR-), were compared for fitness
      parameters on healthy and East African cassava mosaic virus-Uganda variant (EACMV
      UG)-infected cassava plants. The whitefly fecundity and nymph development was not
      affected by bacterial infections or the infection of cassava by the virus.
      However, emergence of adults from nymphs was 50 and 17% higher by AR- on healthy
      and virus-infected plants, respectively, than AR+ flies. Development time of
      adults also was 10 days longer in AR+ than AR-. The whiteflies were further
      compared for acquisition and retention of EACMV-UG. Higher proportion of AR-
      acquired (91.8%) and retained (87.6%) the virus than AR+ (71.8, 61.2%,
      respectively). Similarly, the AR- flies retained higher quantities of virus
      (~ninefold more) than AR+. These results indicated that bacteria-free whiteflies
      were superior and better transmitters of EACMV-UG, as they had higher adult
      emergence, quicker life cycle and better virus retention abilities than those
      infected with bacteria.

PMID- 29367841
TI  - Effect of synthetic hormones on reproduction in Mastomys natalensis.
AB  - Rodent pest management traditionally relies on some form of lethal control.
      Developing effective fertility control for pest rodent species could be a major
      breakthrough particularly in the context of managing rodent population outbreaks.
      This laboratory-based study is the first to report on the effects of using
      fertility compounds on an outbreaking rodent pest species found throughout sub
      Saharan Africa. Mastomys natalensis were fed bait containing the synthetic
      steroid hormones quinestrol and levonorgestrel, both singly and in combination,
      at three concentrations (10, 50, 100 ppm) for 7 days. Consumption of the bait and
      animal body mass was mostly the same between treatments when analysed by sex, day
      and treatment. However, a repeated measures ANOVA indicated that quinestrol and
      quinestrol + levonorgestrel treatments reduced consumption by up to 45%,
      particularly at the higher concentrations of 50 and 100 ppm. Although there was
      no clear concentration effect on animal body mass, quinestrol and quinestrol +
      levonorgestrel lowered body mass by up to 20% compared to the untreated and
      levonorgestrel treatments. Quinestrol and quinestrol + levonorgestrel reduced the
      weight of male rat testes, epididymis and seminal vesicles by 60-80%, and sperm
      concentration and motility were reduced by more than 95%. No weight changes were
      observed to uterine and ovarian tissue; however, high uterine oedema was observed
      among all female rats consuming treated bait at 8 and 40 days from trial start.
      Trials with mate pairing showed there were significant differences in the
      pregnancy rate with all treatments when compared to the untreated control group
      of rodents.

PMID- 29367842
TI  - Direct and indirect influences of intercrops on the coconut defoliator Opisina
      arenosella.
AB  - Coconut palm (Cocos nucifera) infestation by Opisina arenosella (Lepidoptera:
      Oecophoridae) in the Indian subcontinent may occur in November to May each year
      in the same or adjoining areas of plantations. Parasitoids of O. arenosella may
      also be consistently present at these times. During other periods, pests and/or
      parasitoids could be maintained on intercrops that are commonly grown throughout
      the year. Field surveys of 54 intercrop species in Kerala, India, found that O.
      arenosella attacks banana, but not others, while laboratory screening showed that
      O. arenosella can mature on jack fruit, cashew and oil palm. Larvae of 20
      lepidopteran species found on intercrops were screened for use by Goniozus
      nephantidis (Hymenoptera: Bethylidae), a larval parasitoid of O. arenosella,
      which oviposited on two species but its offspring failed to mature. Thirteen
      intercrop herbivore species were screened for use by Brachymeria nosatoi
      (Hymenoptera: Chalcididae), a pupal parasitoid of O. arenosella, which completed
      development on the pyralids Herculia nigrivita, Syllepte derogata and Psara
      basalis. Further, connectance trophic webs were compiled using prior field
      records of coconut, 33 species of intercrops, 58 species of lepidopteran
      herbivores and 29 species of primary parasitoids. Both laboratory and literature
      evidence suggests that populations of O. arenosella are unlikely to be maintained
      by feeding on intercrops or strongly influenced by direct competition with other
      lepidopterans but are likely to be affected by sharing parasitoids. Intercrop
      herbivores have clear potential for maintaining parasitoids of O. arenosella, and
      we recommend thirteen plant species as intercrops that should aid in conservation
      biocontrol.

PMID- 29367843
TI  - DnaJ/Hsp40 Family and Parkinson's Disease.
AB  - Parkinson's disease (PD) is the second most common devastating neurodegenerative
      disorder after Alzheimer's disease. The precise molecular and cellular basis
      underlying PD still remains uncertain; however, accumulating evidence suggests
      that neuronal cell death is caused by a combination of environmental and genetic
      factors. Over the previous two decades, more than 20 genes have been identified
      as the cause of and/or risk for PD. Because sporadic and familial forms of PD
      have many similarities in clinical and neuropathological features, common
      molecular pathways, such as aberrant mitochondrial and protein homeostasis, are
      likely to exist in both conditions. Of the various genes and proteins involved in
      PD, the versatile DnaJ/Hsp40 co-chaperones have attracted particular attention
      since several genes encoding this protein family have been successively
      identified as the cause of the familial forms of PD/Parkinsonism. In this review,
      we will introduce the current knowledge regarding the integratory and modulatory
      effect of DnaJ/Hsp40 in various cellular functions and argue how the failure of
      these proteins may initiate and/or facilitate of the disease.

PMID- 29367844
TI  - Electroencephalography Amplitude Modulation Analysis for Automated Affective
      Tagging of Music Video Clips.
AB  - The quantity of music content is rapidly increasing and automated affective
      tagging of music video clips can enable the development of intelligent retrieval,
      music recommendation, automatic playlist generators, and music browsing
      interfaces tuned to the users' current desires, preferences, or affective states.
      To achieve this goal, the field of affective computing has emerged, in particular
      the development of so-called affective brain-computer interfaces, which measure
      the user's affective state directly from measured brain waves using non-invasive
      tools, such as electroencephalography (EEG). Typically, conventional features
      extracted from the EEG signal have been used, such as frequency subband powers
      and/or inter-hemispheric power asymmetry indices. More recently, the coupling
      between EEG and peripheral physiological signals, such as the galvanic skin
      response (GSR), have also been proposed. Here, we show the importance of EEG
      amplitude modulations and propose several new features that measure the amplitude
      amplitude cross-frequency coupling per EEG electrode, as well as linear and non
      linear connections between multiple electrode pairs. When tested on a publicly
      available dataset of music video clips tagged with subjective affective ratings,
      support vector classifiers trained on the proposed features were shown to
      outperform those trained on conventional benchmark EEG features by as much as 6,
      20, 8, and 7% for arousal, valence, dominance and liking, respectively. Moreover,
      fusion of the proposed features with EEG-GSR coupling features showed to be
      particularly useful for arousal (feature-level fusion) and liking (decision-level
      fusion) prediction. Together, these findings show the importance of the proposed
      features to characterize human affective states during music clip watching.

PMID- 29367845
TI  - Reproducibility of Heart Rate Variability Is Parameter and Sleep Stage Dependent.
AB  - Objective: Measurements of heart rate variability (HRV) during sleep have become
      increasingly popular as sleep could provide an optimal state for HRV assessments.
      While sleep stages have been reported to affect HRV, the effect of sleep stages
      on the variance of HRV parameters were hardly investigated. We aimed to assess
      the variance of HRV parameters during the different sleep stages. Further, we
      tested the accuracy of an algorithm using HRV to identify a 5-min segment within
      an episode of slow wave sleep (SWS, deep sleep). Methods: Polysomnographic (PSG)
      sleep recordings of 3 nights of 15 healthy young males were analyzed. Sleep was
      scored according to conventional criteria. HRV parameters of consecutive 5-min
      segments were analyzed within the different sleep stages. The total variance of
      HRV parameters was partitioned into between-subjects variance, between-nights
      variance, and between-segments variance and compared between the different sleep
      stages. Intra-class correlation coefficients of all HRV parameters were
      calculated for all sleep stages. To identify an SWS segment based on HRV, Pearson
      correlation coefficients of consecutive R-R intervals (rRR) of moving 5-min
      windows (20-s steps). The linear trend was removed from the rRR time series and
      the first segment with rRR values 0.1 units below the mean rRR for at least 10
      min was identified. A 5-min segment was placed in the middle of such an
      identified segment and the corresponding sleep stage was used to assess the
      accuracy of the algorithm. Results: Good reproducibility within and across nights
      was found for heart rate in all sleep stages and for high frequency (HF) power in
      SWS. Reproducibility of low frequency (LF) power and of LF/HF was poor in all
      sleep stages. Of all the 5-min segments selected based on HRV data, 87% were
      accurately located within SWS. Conclusions: SWS, a stable state that, in contrast
      to waking, is unaffected by internal and external factors, is a reproducible
      state that allows reliable determination of heart rate, and HF power, and can
      satisfactorily be detected based on R-R intervals, without the need of full PSG.
      Sleep may not be an optimal condition to assess LF power and LF/HF power ratio.

PMID- 29367846
TI  - Reduction of Endothelial Nitric Oxide Increases the Adhesiveness of Constitutive
      Endothelial Membrane ICAM-1 through Src-Mediated Phosphorylation.
AB  - Nitric oxide (NO) is a known anti-adhesive molecule that prevents platelet
      aggregation and leukocyte adhesion to endothelial cells (ECs). The mechanism has
      been attributed to its role in the regulation of adhesion molecules on leukocytes
      and the adhesive properties of platelets. Our previous study conducted in rat
      venules found that reduction of EC basal NO synthesis caused EC ICAM-1-mediated
      firm adhesion of leukocytes within 10-30 min. This quick response occurred in the
      absence of alterations of adhesion molecules on leukocytes and also opposes the
      classical pattern of ICAM-1-mediated leukocyte adhesion that requires protein
      synthesis and occurs hours after stimulation. The objective of this study is to
      investigate the underlying mechanisms of reduced basal NO-induced EC-mediated
      rapid leukocyte adhesion observed in intact microvessels. The relative levels of
      ICAM-1 at different cell regions and their activation status were determined with
      cellular fractionation and western blot using cultured human umbilical vein ECs.
      ICAM-1 adhesiveness was determined by immunoprecipitation in non-denatured
      proteins to assess the changes in ICAM-1 binding to its inhibitory antibody,
      mAb1A29, and antibody against total ICAM-1 with and without NO reduction. The
      adhesion strength of EC ICAM-1 was assessed by atomic force microscopy (AFM) on
      live cells. Results showed that reduction of EC basal NO caused by the
      application of caveolin-1 scaffolding domain (AP-CAV) or NOS inhibitor, L-NMMA,
      for 30 min significantly increased phosphorylated ICAM-1 and its binding to
      mAb1A29 in the absence of altered ICAM-1 expression and its distribution at
      subcellular regions. The Src inhibitor, PP1, inhibited NO reduction-induced
      increases in ICAM-1 phosphorylation and adhesive binding. AFM detected
      significant increases in the binding force between AP-CAV-treated ECs and mAb1A29
      coated probes. These results demonstrated that reduced EC basal NO lead to a
      rapid increase in ICAM-1 adhesive binding via Src-mediated phosphorylation
      without de novo protein synthesis and translocation. This study suggests that a
      NO-dependent conformational change of constitutive EC membrane ICAM-1 might be
      the mechanism of rapid ICAM-1 dependent leukocyte adhesion observed in vivo. This
      new mechanistic insight provides a better understanding of EC/leukocyte
      interaction-mediated vascular inflammation under many disease conditions that
      encounter reduced basal NO in the circulation system.

PMID- 29367848
TI  - Aging and Work Ability: The Moderating Role of Job and Personal Resources.
AB  - Objective: Demographic changes involving western countries and later retirements
      due to the recent pension reforms induce a gradual aging of the workforce. This
      imply an increasing number of workers with health problems and a decreasing of
      ability to work. In this direction, the present study aims at examining the role
      of job and personal resources between age and work ability within nurses. Method:
      The study was cross-sectional and not randomized; data were collected by a self
      report questionnaire during a multi-center survey conducted in two Italian
      hospitals in 2016. In this way, 333 nurses were reached. Results: Multiple linear
      regression showed that age is significantly and negatively associated to work
      ability, and that job resources (e.g., decision authority and meaning of work)
      and personal resources (e.g., hope and resilience) moderate the relationship
      between age and work ability. Discussion: These results highlight that investing
      in work and personal resources to support WA is even more relevant for those
      professions where high physical effort is required.

PMID- 29367847
TI  - Brain Structure and Function in Women with Comorbid Bipolar and Premenstrual
      Dysphoric Disorder.
AB  - Introduction: Hormonal fluctuations associated with female reproductive life
      events may precipitate or worsen affective episodes in women with bipolar
      disorder (BD). Previous studies have shown that women with BD report higher rates
      of premenstrual dysphoric disorder (PMDD) than controls. Further, bipolar women
      who report premenstrual worsening of mood display a worse course of their bipolar
      illness. Despite this, the neural correlates of comorbid BD and PMDD have not
      been investigated. Methodology: Eighty-five [CTRL, n = 25; PMDD, n = 20; BD, n =
      21; BD with comorbid PMDD (BDPMDD), n = 19], regularly cycling women, not on
      hormonal contraception, underwent two MRI scans: during their mid-follicular and
      late luteal menstrual phases. We investigated resting-state functional
      connectivity (Rs-FC), cortical thickness, and subcortical volumes of brain
      regions associated with the pathophysiology of BD and PMDD between groups, in the
      mid-follicular and late luteal phases of the menstrual cycle. All BD subjects
      were euthymic for at least 2 months prior to study entry. Results: Women in the
      BDPMDD group displayed greater disruption in biological rhythms and more
      subthreshold depressive and anxious symptoms through the menstrual cycle compared
      to other groups. Rs-FC was increased between the L-hippocampus and R-frontal
      cortex and decreased between the R-hippocampus and R-premotor cortex in BDPMDD
      vs. BD (FDR-corrected, p < 0.05). Cortical thickness analysis revealed decreased
      cortical thickness of the L-pericalcarine, L-superior parietal, R-middle
      temporal, R-rostral middle frontal, and L-superior frontal, as well as increased
      cortical thickness of the L-superior temporal gyri in BDPMDD compared to BD. We
      also found increased left-caudate volume in BDPMDD vs. BD (pCORR < 0.05).
      Conclusion: Women with BD and comorbid PMDD display a distinct clinical and
      neurobiological phenotype of BD, which suggests differential sensitivity to
      endogenous hormones.

PMID- 29367849
TI  - How Will We React to the Discovery of Extraterrestrial Life?
AB  - How will humanity react to the discovery of extraterrestrial life? Speculation on
      this topic abounds, but empirical research is practically non-existent. We report
      the results of three empirical studies assessing psychological reactions to the
      discovery of extraterrestrial life using the Linguistic Inquiry and Word Count
      (LIWC) text analysis software. We examined language use in media coverage of past
      discovery announcements of this nature, with a focus on extraterrestrial
      microbial life (Pilot Study). A large online sample (N = 501) was asked to write
      about their own and humanity's reaction to a hypothetical announcement of such a
      discovery (Study 1), and an independent, large online sample (N = 256) was asked
      to read and respond to a newspaper story about the claim that fossilized
      extraterrestrial microbial life had been found in a meteorite of Martian origin
      (Study 2). Across these studies, we found that reactions were significantly more
      positive than negative, and more reward vs. risk oriented. A mini-meta-analysis
      revealed large overall effect sizes (positive vs. negative affect language: g =
      0.98; reward vs. risk language: g = 0.81). We also found that people's forecasts
      of their own reactions showed a greater positivity bias than their forecasts of
      humanity's reactions (Study 1), and that responses to reading an actual
      announcement of the discovery of extraterrestrial microbial life showed a greater
      positivity bias than responses to reading an actual announcement of the creation
      of man-made synthetic life (Study 2). Taken together, this work suggests that our
      reactions to a future confirmed discovery of microbial extraterrestrial life are
      likely to be fairly positive.

PMID- 29367850
TI  - Hot and Cool Executive Functions in Adolescence: Development and Contributions to
      Important Developmental Outcomes.
AB  - Despite significant theoretical advancement in the area of child neuropsychology,
      limited attention has been paid to the developmental features of adolescence. The
      present study intends to address this issue in relation to executive function
      (EF). EF refers to the psychological processes that underlie goal-directed
      behavior; recent studies separate cool EF (psychological process involves pure
      logic and critical analysis) and hot EF (psychological process driven by
      emotion). Although neurological findings suggest that adolescence is a sensitive
      period for EF development, data on comparing the developmental progression in hot
      or cool EFs is highly missing. Moreover, while evidence has confirmed the
      relationships between EF and day-to-day functioning, whether and how hot and cool
      EFs contribute to core developmental outcomes in adolescence is still remained
      unknown. The current study aims to enhance our understanding of the development
      and impacts of hot and cool EFs in adolescence. A total of 136 typically
      developing adolescents from age 12 to 17 completed four cool EF tasks including
      Backward digit span, Contingency naming test, Stockings of Cambridge, and Stroop
      Color and Word test, and one hot task on Cambridge gambling task. Data on
      academic performance and psychological adjustment was also collected. Results
      showed that cool and hot EF exhibited different patterns of age-related growth in
      adolescence. Specifically, cool EF ascended with age while hot EF showed a bell
      shaped development. Moreover, there were correlations among cool EF measures but
      no association between cool and hot EFs. Further, cool EF was a better predictor
      of academic performance, while hot EF uniquely related to emotional problems. The
      results provide evidence for the association among cool EF tests and the
      differentiation of hot and cool EFs. The bell-shaped development of hot EF might
      suggest a period of heightened risk-taking propensity in middle adolescence.
      Given the plastic nature of EF, especially over adolescence, the current findings
      may have practical implications for future EF identification and training.

PMID- 29367851
TI  - Hemiface Differences in Visual Exploration Patterns When Judging the Authenticity
      of Facial Expressions.
AB  - Past studies have found asymmetry biases in human emotion recognition. The left
      side bias refers to preferential looking at the left-hemiface when actively
      exploring face images. However, these studies have been mainly conducted with
      static and frontally oriented stimuli, whereas real-life emotion recognition
      takes place on dynamic faces viewed from different angles. The aim of this study
      was to assess the judgment of genuine vs. masked expressions in dynamic movie
      clips of faces rotated to the right or left side. Forty-eight participants judged
      the expressions on faces displaying genuine or masked happy, sad, and fearful
      emotions. The head of the actor was either rotated to the left by a 45 degrees 
      angle, thus showing the left side of the face (standard orientation), or
      inverted, with the same face shown from the right side perspective. The eye
      movements were registered by the eye tracker and the data were analyzed for the
      inverse efficiency score (IES), the number of fixations, gaze time on the whole
      face and in the regions of interest. Results showed shorter IESs and gaze times
      for happy compared to sad and fearful emotions, but no difference was found for
      these variables between sad and fearful emotions. The left side preference was
      evident from comparisons of the number of fixations. Standard stimuli received a
      higher number of fixations than inverted ones. However, gaze time was long on
      inverted compared to standard faces. Number of fixations on exposed hemiface
      interacted with the emotions decreasing from happy to sad and fearful. An
      opposite pattern was found for the occluded hemiface. These results suggest a
      change in fixation patterns in the rotated faces that may be beneficial for the
      judgments of expressions. Furthermore, this study replicated the effects of the
      judgment of genuine and masked emotions using dynamic faces.

PMID- 29367852
TI  - Pichia pastoris-Expressed Bivalent Virus-Like Particulate Vaccine Induces Domain
      III-Focused Bivalent Neutralizing Antibodies without Antibody-Dependent
      Enhancement in Vivo.
AB  - Dengue, a significant public health problem in several countries around the
      world, is caused by four different serotypes of mosquito-borne dengue viruses
      (DENV-1, -2, -3, and -4). Antibodies to any one DENV serotype which can protect
      against homotypic re-infection, do not offer heterotypic cross-protection. In
      fact, cross-reactive antibodies may augment heterotypic DENV infection through
      antibody-dependent enhancement (ADE). A recently launched live attenuated vaccine
      (LAV) for dengue, which consists of a mixture of four chimeric yellow
      fever/dengue vaccine viruses, may be linked to the induction of disease-enhancing
      antibodies. This is likely related to viral interference among the replicating
      viral strains, resulting in an unbalanced immune response, as well as to the fact
      that the LAV encodes prM, a DENV protein documented to elicit ADE-mediating
      antibodies. This makes it imperative to explore the feasibility of alternate ADE
      risk-free vaccine candidates. Our quest for a non-replicating vaccine centered on
      the DENV envelope (E) protein which mediates virus entry into the host cell and
      serves as an important target of the immune response. Serotype-specific
      neutralizing epitopes and the host receptor recognition function map to E domain
      III (EDIII). Recently, we found that Pichia pastoris-expressed DENV E protein, of
      all four serotypes, self-assembled into virus-like particles (VLPs) in the
      absence of prM. Significantly, these VLPs displayed EDIII and elicited EDIII
      focused DENV-neutralizing antibodies in mice. We now report the creation and
      characterization of a novel non-replicating recombinant particulate vaccine
      candidate, produced by co-expressing the E proteins of DENV-1 and DENV-2 in P.
      pastoris. The two E proteins co-assembled into bivalent mosaic VLPs (mVLPs)
      designated as mE1E2bv VLPs. The mVLP, which preserved the serotype-specific
      antigenic integrity of its two component proteins, elicited predominantly EDIII
      focused homotypic virus-neutralizing antibodies in BALB/c mice, demonstrating its
      efficacy. In an in vivo ADE model, mE1E2bv VLP-induced antibodies lacked
      discernible ADE potential, compared to the cross-reactive monoclonal antibody
      4G2, as evidenced by significant reduction in the levels of IL-6 and TNF-alpha,
      suggesting inherent safety. The results obtained with these bivalent mVLPs
      suggest the feasibility of incorporating the E proteins of DENV-3 and DENV-4 to
      create a tetravalent mVLP vaccine.

PMID- 29367853
TI  - B Cell-Intrinsic Role for IRF5 in TLR9/BCR-Induced Human B Cell Activation,
      Proliferation, and Plasmablast Differentiation.
AB  - Upon recognition of antigen, B cells undergo rapid proliferation followed by
      differentiation to specialized antibody secreting cells (ASCs). During this
      transition, B cells are reliant upon a multilayer transcription factor network to
      achieve a dramatic remodeling of the B cell transcriptional landscape. Increased
      levels of ASCs are often seen in autoimmune diseases and it is believed that
      altered expression of regulatory transcription factors play a role in this
      imbalance. The transcription factor interferon regulatory factor 5 (IRF5) is one
      such candidate as polymorphisms in IRF5 associate with risk of numerous
      autoimmune diseases and correlate with elevated IRF5 expression. IRF5 genetic
      risk has been widely replicated in systemic lupus erythematosus (SLE), and loss
      of Irf5 ameliorates disease in murine lupus models, in part, through the lack of
      pathogenic autoantibody secretion. It remains unclear, however, whether IRF5 is
      contributing to autoantibody production through a B cell-intrinsic function. To
      date, IRF5 function in healthy human B cells has not been characterized. Using
      human primary naive B cells, we define a critical intrinsic role for IRF5 in B
      cell activation, proliferation, and plasmablast differentiation. Targeted IRF5
      knockdown resulted in significant immunoglobulin (Ig) D retention, reduced
      proliferation, plasmablast differentiation, and IgG secretion. The observed
      decreases were due to impaired B cell activation and clonal expansion. Distinct
      from murine studies, we identify and confirm new IRF5 target genes, IRF4, ERK1,
      and MYC, and pathways that mediate IRF5 B cell-intrinsic function. Together,
      these results identify IRF5 as an early regulator of human B cell activation and
      provide the first dataset in human primary B cells to map IRF5 dysfunction in
      SLE.

PMID- 29367854
TI  - The Contribution of Cytomegalovirus Infection to Immune Senescence Is Set by the
      Infectious Dose.
AB  - The relationship between human cytomegalovirus (HCMV) infections and accelerated
      immune senescence is controversial. Whereas some studies reported a CMV
      associated impaired capacity to control heterologous infections at old age, other
      studies could not confirm this. We hypothesized that these discrepancies might
      relate to the variability in the infectious dose of CMV occurring in real life.
      Here, we investigated the influence of persistent CMV infection on immune
      perturbations and specifically addressed the role of the infectious dose on the
      contribution of CMV to accelerated immune senescence. We show in experimental
      mouse models that the degree of mouse CMV (MCMV)-specific memory CD8+ T cell
      accumulation and the phenotypic T cell profile are directly influenced by the
      infectious dose, and data on HCMV-specific T cells indicate a similar connection.
      Detailed cluster analysis of the memory CD8+ T cell development showed that high
      dose infection causes a differentiation pathway that progresses faster throughout
      the life span of the host, suggesting a virus-host balance that is influenced by
      aging and infectious dose. Importantly, short-term MCMV infection in adult mice
      is not disadvantageous for heterologous superinfection with lymphocytic
      choriomeningitis virus (LCMV). However, following long-term CMV infection the
      strength of the CD8+ T cell immunity to LCMV superinfection was affected by the
      initial CMV infectious dose, wherein a high infectious dose was found to be a
      prerequisite for impaired heterologous immunity. Altogether our results
      underscore the importance of stratification based on the size and differentiation
      of the CMV-specific memory T cell pools for the impact on immune senescence, and
      indicate that reduction of the latent/lytic viral load can be beneficial to
      diminish CMV-associated immune senescence.

PMID- 29367855
TI  - Mitochondrial Dysfunction Causes Oxidative Stress and Tapetal Apoptosis in
      Chemical Hybridization Reagent-Induced Male Sterility in Wheat.
AB  - Male sterility in plants has been strongly linked to mitochondrial dysfunction.
      Chemical hybridization agent (CHA)-induced male sterility is an important tool in
      crop heterosis. Therefore, it is important to better understand the relationship
      between mitochondria and CHA-induced male sterility in wheat. This study reports
      on the impairment of mitochondrial function duo to CHA-SQ-1, which occurs by
      decreasing cytochrome oxidase and adenosine triphosphate synthase protein levels
      and theirs activities, respiratory rate, and in turn results in the inhibition of
      the mitochondrial electron transport chain (ETC), excessive production of
      reactive oxygen species (ROS) and disruption of the alternative oxidase pathway.
      Subsequently, excessive ROS combined with MnSOD defects results in damage to the
      mitochondrial membrane, followed by ROS release into the cytoplasm. The
      microspores underwent severe oxidative stress during pollen development.
      Furthermore, chronic oxidative stress, together with the overexpression of type
      II metacaspase, triggered premature tapetal apoptosis, which resulted in pollen
      abortion. Accordingly, we propose a metabolic pathway for mitochondrial-mediated
      male sterility in wheat, which provides information on the molecular events
      underlying CHA-SQ-1-induced abortion of anthers and may serve as an additional
      guide to the practical application of hybrid breeding.

PMID- 29367856
TI  - Soybean NADP-Malic Enzyme Functions in Malate and Citrate Metabolism and
      Contributes to Their Efflux under Al Stress.
AB  - Malate accumulation has been suggested to balance Al-induced citrate synthesis
      and efflux in soybean roots. To test this hypothesis, characteristics of Al
      induced accumulation and efflux of citrate and malate were compared between two
      soybean genotypes combining a functional analysis of GmME1 putatively encode a
      cytosolic NADP-malic enzyme. Similar amounts of citrate were released, and root
      elongation was equally inhibited before 8 h of Al treatment of Jiyu 70 and Jiyu
      62 cultivars. Jiyu 70 began to secrete more citrate and exhibited higher Al
      resistance than did Jiyu 62 at 12 h. A sustained increase in internal malate and
      citrate concentrations was observed in Jiyu 70 at 24 h of Al treatment. However,
      Jiyu 62 decreased its malate concentration at 12 h and its citrate concentration
      at 24 h of Al treatment. GmME1 localized to the cytoplast and clustered closely
      with cytosolic malic enzymes AtME2 and SgME1 and was constitutively expressed in
      the roots. Al treatment induced higher NADP-malic enzyme activities and GmME1
      expression levels in Jiyu 70 than in Jiyu 62 within 24 h. Compared with wild-type
      hairy roots, over-expressing GmME1 in hairy roots (GmME1-OE) produced higher
      expression levels of GmME1 but did not change the expression patterns of either
      of the putative citrate transporter genes GmAACT1 and GmFRDL or the malate
      transporter gene GmALMT1, with or without Al treatment. GmME1-OE showed a higher
      internal concentration and external efflux of both citrate and malate at 4 h of
      Al stress. Lighter hematoxylin staining and lower Al contents in root apices of
      GmME1-OE hairy roots indicated greater Al resistance. Comprehensive experimental
      results suggest that sustaining Al-induced citrate efflux depends on the malate
      pool in soybean root apices. GmME1 encodes a cytosolic malic enzyme that
      contributes to increased internal malate and citrate concentrations and their
      external efflux to confer higher Al resistance.

PMID- 29367858
TI  - Proton tracking for medical imaging and dosimetry.
AB  - For many years, silicon micro-strip detectors have been successfully used as
      tracking detectors for particle and nuclear physics experiments. A new
      application of this technology is to the field of particle therapy, where
      radiotherapy is carried out by use of charged particles such as protons or carbon
      ions. Such a treatment has been shown to have advantages over standard x-ray
      radiotherapy and as a result of this, many new centres offering particle therapy
      are currently under construction - including two in the U.K.. The characteristics
      of a new silicon micro-strip detector based system for this application will be
      presented. The array uses specifically designed large area sensors in several
      stations in an x-u-v co-ordinate configuration suitable for very fast proton
      tracking with minimal ambiguities. The sensors will form a tracker capable of
      giving information on the path of high energy protons entering and exiting a
      patient. This will allow proton computed tomography (pCT) to aid the accurate
      delivery of treatment dose with tuned beam profile and energy. The tracker will
      also be capable of proton counting and position measurement at the higher
      fluences and full range of energies used during treatment allowing monitoring of
      the beam profile and total dose. Results and initial characterisation of sensors
      will be presented along with details of the proposed readout electronics.
      Radiation tests and studies with different electronics at the Clatterbridge
      Cancer Centre and the higher energy proton therapy facility of iThemba LABS in
      South Africa will also be shown.

PMID- 29367857
TI  - Co-inoculation of a Pea Core-Collection with Diverse Rhizobial Strains Shows
      Competitiveness for Nodulation and Efficiency of Nitrogen Fixation Are Distinct
      traits in the Interaction.
AB  - Pea forms symbiotic nodules with Rhizobium leguminosarum sv. viciae (Rlv). In the
      field, pea roots can be exposed to multiple compatible Rlv strains. Little is
      known about the mechanisms underlying the competitiveness for nodulation of Rlv
      strains and the ability of pea to choose between diverse compatible Rlv strains.
      The variability of pea-Rlv partner choice was investigated by co-inoculation with
      a mixture of five diverse Rlv strains of a 104-pea collection representative of
      the variability encountered in the genus Pisum. The nitrogen fixation efficiency
      conferred by each strain was determined in additional mono-inoculation
      experiments on a subset of 18 pea lines displaying contrasted Rlv choice.
      Differences in Rlv choice were observed within the pea collection according to
      their genetic or geographical diversities. The competitiveness for nodulation of
      a given pea-Rlv association evaluated in the multi-inoculated experiment was
      poorly correlated with its nitrogen fixation efficiency determined in mono
      inoculation. Both plant and bacterial genetic determinants contribute to pea-Rlv
      partner choice. No evidence was found for co-selection of competitiveness for
      nodulation and nitrogen fixation efficiency. Plant and inoculant for an improved
      symbiotic association in the field must be selected not only on nitrogen fixation
      efficiency but also for competitiveness for nodulation.

PMID- 29367859
TI  - The global problem of child maltreatment: Perspectives on mechanisms of influence
      and illness presentation.
AB  - Child abuse and neglect negatively impact both neurological and psychological
      development. Patterns of abuse are learned and repeated in families. Adverse
      childhood experiences are a risk factor for psychopathology later in life,
      including borderline personality disorder (BPD). BPD is prevalent in clinical
      populations in the United States, but its prevalence has not been well-documented
      in most other parts of the world. The aim of this paper is to explore the impact
      of culture upon the intergenerational transmission of childhood maltreatment and
      the clinical presentation of abused children. To facilitate this exploration, we
      will consider the cases of four adolescent girls in unique socioeconomic and
      cultural settings around the world: Liberia, El Salvador, India, and a Congolese
      immigrant in France. Each of these girls endorsed some features of BPD, but only
      two met full criteria. In societies in which externalizing behaviors are not
      acceptable, children may internalize their distress or separate from their
      families. Defining BPD in terms of internal experience makes it more difficult to
      identify, but it would allow for the inclusion of cases in which symptoms may
      manifest differently while the underlying problem is similar.

PMID- 29367860
TI  - Fentanyls continue to replace heroin in the drug arena: the cases of ocfentanil
      and carfentanil.
AB  - Purpose: Ocfentanil and carfentanil are two potent synthetic opioids that are
      analogues of fentanyl and are actively involved in the recent fentanyl crisis.
      The aim of this review is to provide all the available information on these two
      fentanyl analogues. Methods: All reviewed information was gathered through a
      detailed search of PubMed and the World Wide Web using relevant keywords.
      Results: Like most of the members of the family of fentanyls, they are either
      sold as heroin to unsuspecting users or used extensively to lace heroin street
      samples. Despite the fact that ocfentanil was studied clinically in the early
      1990s, it did not manage to find its place in clinical practice. On the other
      hand, carfentanil is mainly used today as an anesthetic agent in large animals.
      Ocfentanil and carfentanil are used and abused extensively, mainly in Europe and
      in the United States. As a result, they are the cause of some verified
      intoxication cases and deaths worldwide. This review provides information
      concerning chemistry, synthesis, prevalence, pharmacology, and toxicology, as
      well as the current legal status of these two fentanyl analogues. Analytical
      methods developed for the determination of ocfentanil and carfentanil in
      biological specimens and seized materials, as well as related intoxication and
      lethal cases are also presented. Conclusions: Ocfentanil and carfentanil are
      undeniably very dangerous opioid drugs and a very serious matter of concern for
      public safety. The authorities should take the appropriate actions to avoid the
      expansion of this threat by taking proper and prompt measures.

PMID- 29367861
TI  - The newest cathinone derivatives as designer drugs: an analytical and
      toxicological review.
AB  - Purpose: Currently, among new psychoactive substances, cathinone derivatives
      constitute the biggest group, which are mainly classified into N-alkylated, 3,4
      methylenedioxy-N-alkylated, N-pyrrolidinyl, and 3,4-methylenedioxy-N-pyrrolidinyl
      derivatives. These derivatives are actively being subjected to minor
      modifications at the alkyl chains or the aromatic ring to create new synthetic
      cathinones with the goal of circumventing laws. In this review, the new synthetic
      cathinones that have appeared on the illegal drug market during the period 2014
      2017 are highlighted, and their characterization by gas chromatography-mass
      spectrometry and liquid chromatography-tandem mass spectrometry is presented.
      Methods: Various key words were used to conduct an extensive literature search
      across a number of databases, specifically for synthetic cathinones that emerged
      between 2014 and 2017. Results: More than 30 new cathinone derivatives were
      discovered. The preexisting parental compounds for the new derivatives are also
      referenced, and their mass spectral data are compiled in a table to facilitate
      their identification by forensic toxicologists. Conclusions: To our knowledge,
      this is the most current review presenting new synthetic cathinones. Political
      authorities should take measures to implement and enforce generic scheduling
      (comprehensive system) laws to control the diversely modified synthetic
      cathinones. Supplementing the existing databases with new findings can greatly
      facilitate the efforts of forensic toxicologists.

PMID- 29367862
TI  - Evaluation of carboxamide-type synthetic cannabinoids as CB1/CB2 receptor
      agonists: difference between the enantiomers.
AB  - Recently, carboxamide-type synthetic cannabinoids have been distributed globally
      as new psychoactive substances (NPS). Some of these compounds possess asymmetric
      carbon, which is derived from an amide moiety composed of amino acid derivatives
      (i.e., amides or esters of amino acids). In this study, we synthesized both
      enantiomers of synthetic cannabinoids, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(2
      fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA 2-fluorobenzyl isomer), N-(1
      amino-1-oxo-3-phenylpropan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide
      (APP-CHMINACA), ethyl [1-(5-fluoropentyl)-1H-indazole-3-carbonyl]valinate (5F-EMB
      PINACA), ethyl [1-(4-fluorobenzyl)-1H-indazole-3-carbonyl]valinate (EMB
      FUBINACA), and methyl 2-[1-(4-fluorobenzyl)-1H-indole-3-carboxamido]-3,3
      dimethylbutanoate (MDMB-FUBICA), which were reported as NPS found in Europe from
      2014 to 2015, to evaluate their activities as CB1/CB2 receptor agonists. With the
      exception of (R) MDMB-FUBICA, all of the tested enantiomers were assumed to be
      agonists of both CB1 and CB2 receptors, and the EC50 values of the (S)
      enantiomers for the CB1 receptors were about five times lower than those of (R)
      enantiomers. (R) MDMB-FUBICA was shown to function as an agonist of the CB2
      receptor, but lacks CB1 receptor activity. To the best of our knowledge, this is
      the first report to show that the (R)-enantiomers of the carboxamide-type
      synthetic cannabinoids have the potency to activate CB1 and CB2 receptors. The
      findings presented here shed light on the pharmacological properties of these
      carboxamide-type synthetic cannabinoids in forensic cases.

PMID- 29367863
TI  - Fatal sarin poisoning in Syria 2013: forensic verification within an
      international laboratory network.
AB  - During the United Nations fact-finding mission to investigate the alleged use of
      chemical warfare agents in the Syrian Arab Republic in 2013, numerous tissues
      from a deceased female victim, who had displayed symptoms of cholinergic crisis,
      were collected. The Organisation for the Prohibition of Chemical Weapons (OPCW)
      authorized two specialized laboratories in the Netherlands and Germany for
      forensic analysis of these samples. Diverse modern mass spectrometry (MS)-based
      procedures in combination with either liquid chromatography (LC) or gas
      chromatography (GC) separation were applied. A variety of biotransformation
      products of the nerve agent sarin was detected, including the hydrolysis product
      O-isopropyl methylphosphonic acid (IMPA) as well as covalent protein adducts with
      e.g., albumin and human butyrylcholinesterase (hBChE). IMPA was extracted after
      sample acidification by solid-phase extraction and directly analyzed by LC-tandem
      MS with negative electrospray ionization (ESI). Protein adducts were found,
      either by fluoride-induced reactivation applying GC-MS techniques or by LC-MS
      based detection after positive ESI for proteolyzed proteins yielding
      phosphonylated tyrosine residues or a specific phosphonylated hBChE-derived
      nonapeptide. These experimental results provided unambiguous evidence for a
      systemic intoxication and were the first proving the use of sarin in the ongoing
      bellicose conflict. This scenario underlines the requirement for qualified and
      specialized analytical laboratories to face repeated violation of the Chemical
      Weapons Convention.

PMID- 29367864
TI  - Identification and quantification of mepirapim and acetyl fentanyl in authentic
      human whole blood and urine samples by GC-MS/MS and LC-MS/MS.
AB  - Purpose: We encountered a curious case in which two male subjects self
      administered mepirapim plus acetyl fentanyl by different routes, i.e.,
      intravenously and by inhalation. We have thus established a detailed procedure
      for quantification of mepirapim and acetyl fentanyl in whole blood and urine
      specimens using gas chromatography (GC)-tandem mass spectrometry (MS/MS).
      Methods: The GC-MS/MS method was validated for linearity, extraction recovery,
      accuracy, and precision. Liquid chromatography-MS/MS was also used for
      identification of the target compounds. Results: Good linearity and
      reproducibility were achieved in the range of 20-1000 ng/g for both target
      compounds in both matrices. The concentrations of mepirapim in heart whole blood,
      femoral vein whole blood, and urine of the deceased individual with
      administration by intravenous injection were 593, 567, and 527 ng/g,
      respectively; those of acetyl fentanyl were 155, 125, and 126 ng/g, respectively.
      The mepirapim and acetyl fentanyl concentrations in the urine specimen of the
      surviving individual who had administered them by inhalation were 4900 and 570
      ng/g, respectively. Conclusions: To our knowledge, with the exception of a brief
      mention of a mepirapim concentration in a serum sample in emergency medicine,
      there are no reported data on the identification and quantification of mepirapim
      in biological samples. Mepirapim is a new synthetic cannabinoid. The
      concentration profiles of unchanged mepirapim in whole blood and urine were quite
      different and unique. A detailed clarification of such uniqueness is under way in
      our laboratory.

PMID- 29367865
TI  - Spectroscopic and crystallographic characterization of two cathinone derivatives:
      1-(4-fluorophenyl)-2-(methylamino)pentan-1-one (4-FPD) hydrochloride and 1-(4
      methylphenyl)-2-(ethylamino)pentan-1-one (4-MEAP) hydrochloride.
AB  - Purpose: In this study, we performed identification and physicochemical
      characterization of two cathinone derivatives, 4-FPD and 4-MEAP, found in market
      available materials. Methods: The compounds were characterized by electrospray
      ionization ion trap mass spectrometry (MS) in MS2 and MS3 modes, gas
      chromatography-MS, infrared, Raman and ultraviolet-visible spectroscopies, X-ray
      crystallography, differential scanning calorimetry and nuclear magnetic resonance
      spectroscopy. Results: We could obtain detailed and comprehensive physicochemical
      characterization of 4-FPD and 4-MEAP-new cathinone derivatives available on the
      designer drugs market. Conclusions: Dynamic growth in the number of psychoactive
      substances available on the designer drug markets makes it compulsory to obtain
      analytical data allowing unequivocal identification of these drugs in the fastest
      possible way. In this study we presented analytical data useful in quick
      identification of the investigated compounds.

PMID- 29367866
TI  - Spectroscopic characterization and crystal structures of two cathinone
      derivatives: 1-(4-chlorophenyl)-2-(1-pyrrolidinyl)-pentan-1-one (4-chloro-alpha
      PVP) sulfate and 1-(4-methylphenyl)-2-(dimethylamino)-propan-1-one (4-MDMC)
      hydrochloride salts, seized on illicit drug market.
AB  - Purpose: Two compounds newly found in the seizures by drug enforcement agencies
      were identified and characterized by various instrumental analytical methods.
      Methods: The obtained powder samples were analyzed by gas chromatography-mass
      spectrometry (GC-MS), liquid chromatography-mass spectrometryn (LC-MSn), nuclear
      magnetic resonance (NMR) spectroscopy, infrared and Raman spectroscopy and X-ray
      crystallography. Results: The two compounds were tentatively identified as 4
      chloro-alpha-PVP and 4-MDMC by GC-MS, and LC-MS/MS. The confirmation of the
      results was made by NMR spectroscopy. The X-ray crystallography gave information
      that 4-chloro-alpha-PVP and 4-MDMC were in salted forms with sulfate and
      hydrochloride, respectively; in addition, both compounds existed as racemic
      mixtures. Conclusions: We could identify 4-chloro-alpha-PVP and 4-MDMC in the
      seizure powder samples by various analytical methods. X-ray crystallography was
      especially useful for identifying the salted forms and enantiomeric forms.

PMID- 29367867
TI  - Berries and other natural products in the pancreatic cancer chemoprevention in
      human clinical trials.
AB  - Pancreatic ductal adenocarcinoma (PDAC) was the 12th and 11th most common cancer
      in men and women worldwide in 2012, with the highest incidence in North America
      and Europe and the lowest in Africa and Asia. Due to the lack of efficient early
      diagnosis and rapid disease progression, PDAC patients have a 5-year survival
      rate of just 5%. Epidemiological studies suggest that smoking, obesity, type II
      diabetes, and pancreatitis are common risk factors for PDAC development. By
      contrast, high intake of fresh fruit, vegetables, and nuts rich in phytochemicals
      could reduce PDAC risk. This review summarizes the human clinical studies that
      have used berries or other natural products for chemoprevention of PDAC.
      Developing chemopreventive agents against PDAC would be tremendously valuable for
      the high-risk population and patients with premalignant lesions. Although some
      clinical trials of these agents have been completed, most are in early phases,
      and the results are not promising, which may be due to administration of the
      natural products at advanced stages of PDAC. Thus, further mechanistic studies
      using genetic animal models that recapitulate the tumor microenvironment and
      immunology of human PDAC would be informative for selecting an effective window
      for intervention with berries or other natural compounds.

PMID- 29367868
TI  - The Effects of Heuristics and Apophenia on Probabilistic Choice.
AB  - Given a repeated choice between two or more options with independent and
      identically distributed reward probabilities, overall pay-offs can be maximized
      by the exclusive selection of the option with the greatest likelihood of reward.
      The tendency to match response proportions to reward contingencies is suboptimal.
      Nevertheless, this behaviour is well documented. A number of explanatory accounts
      have been proposed for probability matching. These include failed pattern
      matching, driven by apophenia, and a heuristic-driven response that can be
      overruled with sufficient deliberation. We report two experiments that were
      designed to test the relative effects on choice behaviour of both an intuitive
      versus strategic approach to the task and belief that there was a predictable
      pattern in the reward sequence, through a combination of both direct experimental
      manipulation and post-experimental self-report. Mediation analysis was used to
      model the pathways of effects. Neither of two attempted experimental
      manipulations of apophenia, nor self-reported levels of apophenia, had a
      significant effect on proportions of maximizing choices. However, the use of
      strategy over intuition proved a consistent predictor of maximizing, across all
      experimental conditions. A parallel analysis was conducted to assess the effect
      of controlling for individual variance in perceptions of reward contingencies.
      Although this analysis suggested that apophenia did increase probability matching
      in the standard task preparation, this effect was found to result from an
      unforeseen relationship between self-reported apophenia and perceived reward
      probabilities. A Win-Stay Lose-Shift (WSLS ) analysis indicated no reliable
      relationship between WSLS and either intuition or strategy use.

PMID- 29367869
TI  - Clinical profile of 300 men with facial hypermelanosis.
AB  - Background: Facial hypermelanosis is a significant cause of cosmetic
      disfigurement, social embarrassment and psychological morbidity affecting quality
      of life. Objective: To study clinicoepidemlogic patterns of facial hypermelanoses
      among men. Material and Methods: Medical records of all adult males presenting
      with facial hypermelanoses were analyzed for this retrospective cross sectional
      study for demographic details, duration, cosmetic usage, sun exposure, drug
      intake, infections, systemic or cutaneous diseases, and family history of
      hypermelanotic dermatosis. Laboratory investigations and skin biopsy were
      performed when deemed necessary. Results: These were 300 Indian men aged 18 to 74
      (mean 37.35) years with 121 (40.3%) individuals aged 31-50 years. Various
      patterns of melasma in 230 (76.7%) patients were the major cause of facial
      hypermelanosis. Periorbital hypermelanosis was observed in 32 (10.7%), freckles
      and lentigens in 26 (8.7%), acanthosis nigricans in 12 (4%) and lichen planus
      pigmentosus in 10 (3.3%), pigmented cosmetic contact dermatitis in 7, and nevus
      of Ota in 6 persons. The 71 (30.8%) patients with melasma had a history of
      frequent sun exposure, 9 (3.9%) patients had systemic comorbidities. Family
      history of periorbital melanosis was present in 7 (21.8%), personal or family
      history of atopy in 5 (15.6%) patients. Acanthosis nigricans was associated with
      obesity in 9 (75%) of patients and with diabetes mellitus in 4 (33.3%) cases.
      Conclusions: Melasma, periorbital hypermelanosis, acanthosis nigricans and lichen
      planus pigmentosus remain the predominant causes for facial hypermelanosis in
      men.

PMID- 29367871
TI  - Rapid clearance of erythrodermic psoriasis with apremilast.
AB  - Background: Apremilast is a new immunomodulatory drug, a small molecule inhibitor
      of PDE4, which down-regulates the expression of multiple pro-inflammatory
      cytokines, such as tumor necrosis factor alpha, interleukin 17, interleukin 23.
      Main observations: We describe a case of a 54-year-old man with erythroderma in
      the course of psoriasis (PASI=49), with contraindications to other psoriasis
      therapies, in whom total clearance of skin lesions was achieved by day 20 after
      therapy with apremilast at a dose of 30 mg bid (DeltaPASI = 100). The patient had
      a history of prior use of cyclosporine, methotrexate and adalimumab. His
      comorbidities included obesity, fatty liver and hypercholesterolemia. Conclusion:
      In this case of erythroderma in the course of psoriasis apremilast led to total
      clearance of all cutaneous lesions.

PMID- 29367870
TI  - Epstein-Barr virus-related cutaneous necrotizing vasculitis in a girl
      heterozygous for factor V Leiden.
AB  - Background: Necrotizing vasculitides are basically characterized by vessel wall
      neutrophil infiltration and necrosis and they can occur as a primary process or
      secondary to an underlying disease. Although Henoch-Schonlein purpura (HSp) is
      the more frequent primary vasculitis in childhood, sometimes it has to be
      distinguished from other secondary vasculitides induced by infections, drugs,
      vaccines, or immune-mediated disorders. Main observations: We report a case of a
      14-year-old girl with cutaneous necrotizing vasculitis, appearing in the course
      of acute Epstein-Barr virus infection. Physical examination revealed highly
      aching erythematous-purple lesions with reticular edges localized on the back of
      feet. Pain was non-responsive to ibuprofen and required administration of
      tapentadol and pregabalin. The patient was also heterozygous for factor V Leiden
      that might have contributed to the development of cutaneous painful lesions.
      Conclusions: To our knowledge this is the first documented pediatric case of
      necrotizing vasculitis associated with acute EBV infection in a girl heterozygous
      for factor V Leiden. In this patient the severity of skin manifestations might
      have been influenced by the concomitant factor V Leiden, which gave rise to
      hypercoagulability and occlusive vasculopathy with markedly severe pain, a
      symptom rather infrequent in other childhood vasculitides.

PMID- 29367872
TI  - Photoletter to the editor: Atypical primary cutaneous mucormycosis of the scalp.
AB  - Mucormycosis of the scalp is a rare cutaneous presentation of the disease. It is
      also an unusual infection in children. We present the case of a 4-year-old girl
      with acute lymphoblastic leukemia, who presented with atypical cutaneous
      mucormycosis simulating an ecthyma gangrenosum lesion. Risk factors for the
      infection are diabetes, neoplastic diseases, immunosuppression in organ
      transplant recipients, and neutropenia. The cutaneos forms have been associated
      with trauma, burns and surgical wounds. First line treatment is amphotericin B.
      Posaconazole was recently approved to treat invasive mucormycosis. Surgical
      removal of the infected tissue is indicated.

PMID- 29367873
TI  - Relative contributions of hydraulic dysfunction and carbohydrate depletion during
      tree mortality caused by drought.
AB  - Drought-induced tree mortality has been observed worldwide. Nevertheless, the
      physiological mechanisms underlying this phenomenon are still being debated.
      Potted Robinia pseudoacacia and Platycladus orientalis saplings were subjected to
      drought and their hydraulic failure and carbon starvation responses were studied.
      They underwent simulated fast drought (FD) and slow drought (SD) until death. The
      dynamics of their growth, photosynthesis, water relations and carbohydrate
      concentration were measured. The results showed that during drought, growth and
      photosynthesis of all saplings were significantly reduced in both species. The
      predawn water potential in both species was ~ -8 MPa at mortality. The percentage
      loss of conductivity (PLC) was at a maximum at mortality under both FD and SD.
      For R. pseudoacacia and P. orientalis, they were >95 and ~45 %, respectively. At
      complete defoliation, the PLC of R. pseudoacacia was ~90 % but the trees
      continued to survive for around 46 days. The non-structural carbohydrate (NSC)
      concentrations in the stems and roots of both FD and SD R. pseudoacacia declined
      to a very low level near death. In contrast, the NSC concentrations in the
      needles, stems and roots of P. orientalis at mortality under FD did not
      significantly differ from those of the control, whereas the NSC concentrations in
      SD P. orientalis stems and roots at death were significantly lower than those of
      the control. These results suggest that the duration of the drought affected NSC
      at mortality in P. orientalis. In addition, the differences in NSC between FD and
      SD P. orientalis did not alter mortality thresholds associated with hydraulic
      failure. The drought-induced death of R. pseudoacacia occurred at 95 % PLC for
      both FD and SD, indicating that hydraulic failure played an important role in
      mortality. Nevertheless, the consistent decline in NSC in R. pseudoacacia
      saplings following drought-induced defoliation may have also contributed to its
      mortality.

PMID- 29367875
TI  - Myotonic dystrophy type 1 with diabetes mellitus, mixed hypogonadism and adrenal
      insufficiency.
AB  - : Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease
      affecting muscles, the eyes and the endocrine organs. Diabetes mellitus and
      primary hypogonadism are endocrine manifestations typically seen in patients with
      DM1. Abnormalities of hypothalamic-pituitary-adrenal (HPA) axis have also been
      reported in some DM1 patients. We present a case of DM1 with a rare combination
      of multiple endocrinopathies; diabetes mellitus, a combined form of primary and
      secondary hypogonadism, and dysfunction of the HPA axis. In the present case,
      diabetes mellitus was characterized by severe insulin resistance with
      hyperinsulinemia. Glycemic control improved after modification of insulin
      sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with
      testosterone replacement therapy. Notably, body composition analysis revealed
      increase in muscle mass and decrease in fat mass in our patient. This implies
      that manifestations of hypogonadism could be hidden by symptoms of myotonic
      dystrophy. Our patient had no symptoms associated with adrenal deficiency, so
      adrenal dysfunction was carefully followed up without hydrocortisone replacement
      therapy. In this report, we highlight the necessity for evaluation and treatment
      of multiple endocrinopathies in patients with DM1. Learning points: DM1 patients
      could be affected by a variety of multiple endocrinopathies.Our patients with DM1
      presented rare combinations of multiple endocrinopathies; diabetes mellitus,
      combined form of primary and secondary hypogonadism and dysfunction of HPA
      axis.Testosterone treatment of hypogonadism in patients with DM1 could improve
      body composition.The patients with DM1 should be assessed endocrine functions and
      treated depending on the degree of each endocrine dysfunction.

PMID- 29367874
TI  - Locoregional therapies in cholangiocarcinoma.
AB  - Cholangiocarcinoma is a rare and aggressive malignancy of the biliary tract.
      Complete surgical resection can be curative, but the majority of patients are
      diagnosed with advanced disease and usually die within a year of diagnosis. Most
      deaths are attributable to local disease progression rather than distant
      metastases, supporting the use of locoregional therapies. There is evidence that
      locoregional therapies can provide local tumor control resulting in increased
      survival while avoiding some of the side effects of systemic treatments,
      increasing potential treatment options for patients who may be unsuitable for
      systemic palliative treatments. This review considers the evidence for
      locoregional therapies in cholangiocarcinoma, which can be classified into
      endoscopic, vascular, percutaneous and radiation oncological therapies. Current
      guidelines do not recommend the routine use of locoregional therapies due to a
      lack of prospective data, but the results of ongoing trials are likely to
      increase the evidence base and impact on clinical practice.

PMID- 29367876
TI  - Insulinoma presenting with post-prandial hypoglycaemia following fundoplication.
AB  - : Insulinomas are rare neuroendocrine tumours that classically present with
      fasting hypoglycaemia. This case report discusses an uncommon and challenging
      case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man
      presented with 6 months of post-prandial hypoglycaemia beginning after a
      laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia
      was confirmed during a spontaneous episode and in a mixed-meal test. Localisation
      studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS)
      and gallium dotatate positron emission tomography (68Ga Dotatate PET) were
      consistent with a small insulinoma in the mid-body of the pancreas. The lesion
      was excised and histopathology was confirmed a localised well-differentiated
      neuroendocrine pancreatic neoplasm. There have been no significant episodes of
      hypoglycaemia since. This case highlights several key points. Insulinoma should
      be sought in proven post-prandial hyperinsulinaemic hypoglycaemia - even in the
      absence of fasting hypoglycaemia. The use of nuclear imaging targeting
      somatostatin and GLP1 receptors has improved accuracy of localisation. Despite
      these advances, accurate surgical resection can remain challenging. Learning
      points: Hypoglycaemia is defined by Whipple's triad and can be provoked by
      fasting or mixed-meal tests.Although uncommon, insulinomas can present with post
      prandial hypoglycaemia.In hypoglycaemia following gastrointestinal surgery (i.e.
      bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non
      insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be
      considered.Improved imaging techniques including MRI, endoscopic ultrasound and
      functional nuclear medicine scans aid localisation of insulinomas.Despite
      advances in imaging and surgical techniques, accurate resection of insulinomas
      remains challenging.

PMID- 29367877
TI  - WNT10A variants isolated from Japanese patients with congenital tooth agenesis.
AB  - It has been reported that dozens of WNT10A variants are associated with human
      isolated tooth agenesis, however, little is known about the precise phenotypes.
      In 50 Japanese patients with severe congenital tooth agenesis, we identified 11
      patients with WNT10A variants. Comparing phenotypes between the tooth agenesis
      patients carrying the wild-type and variants of WNT10A, we revealed that the
      development of lateral incisors is relatively susceptive to insufficiency of
      WNT/beta-catenin signaling.

PMID- 29367879
TI  - Advantages of meta-total RNA sequencing (MeTRS) over shotgun metagenomics and
      amplicon-based sequencing in the profiling of complex microbial communities.
AB  - Sequencing-based microbiome profiling aims at detecting and quantifying
      individual members of a microbial community in a culture-independent manner.
      While amplicon-based sequencing (ABS) of bacterial or fungal ribosomal DNA is the
      most widely used technology due to its low cost, it suffers from PCR
      amplification biases that hinder accurate representation of microbial population
      structures. Shotgun metagenomics (SMG) conversely allows unbiased microbiome
      profiling but requires high sequencing depth. Here we report the development of a
      meta-total RNA sequencing (MeTRS) method based on shotgun sequencing of total RNA
      and benchmark it on a human stool sample spiked in with known abundances of
      bacterial and fungal cells. MeTRS displayed the highest overall sensitivity and
      linearity for both bacteria and fungi, the greatest reproducibility compared to
      SMG and ABS, while requiring a ~20-fold lower sequencing depth than SMG. We
      therefore present MeTRS as a valuable alternative to existing technologies for
      large-scale profiling of complex microbiomes.

PMID- 29367878
TI  - Coastal urbanisation affects microbial communities on a dominant marine
      holobiont.
AB  - Host-associated microbial communities play a fundamental role in the life of
      eukaryotic hosts. It is increasingly argued that hosts and their microbiota must
      be studied together as 'holobionts' to better understand the effects of
      environmental stressors on host functioning. Disruptions of host-microbiota
      interactions by environmental stressors can negatively affect host performance
      and survival. Substantial ecological impacts are likely when the affected hosts
      are habitat-forming species (e.g., trees, kelps) that underpin local
      biodiversity. In marine systems, coastal urbanisation via the addition of
      artificial structures is a major source of stress to habitat formers, but its
      effect on their associated microbial communities is unknown. We characterised
      kelp-associated microbial communities in two of the most common and abundant
      artificial structures in Sydney Harbour-pier-pilings and seawalls-and in
      neighbouring natural rocky reefs. The kelp Ecklonia radiata is the dominant
      habitat-forming species along 8000 km of the temperate Australian coast. Kelp
      associated microbial communities on pilings differed significantly from those on
      seawalls and natural rocky reefs, possibly due to differences in abiotic (e.g.,
      shade) and biotic (e.g., grazing) factors between habitats. Many bacteria that
      were more abundant on kelp on pilings belonged to taxa often associated with
      macroalgal diseases, including tissue bleaching in Ecklonia. There were, however,
      no differences in kelp photosynthetic capacity between habitats. The observed
      differences in microbial communities may have negative effects on the host by
      promoting fouling by macroorganisms or by causing and spreading disease over
      time. This study demonstrates that urbanisation can alter the microbiota of key
      habitat-forming species with potential ecological consequences.

PMID- 29367880
TI  - Cytogenomic identification and long-read single molecule real-time (SMRT)
      sequencing of a Bardet-Biedl Syndrome 9 (BBS9) deletion.
AB  - Bardet-Biedl syndrome (BBS) is a recessive disorder characterized by
      heterogeneous clinical manifestations, including truncal obesity, rod-cone
      dystrophy, renal anomalies, postaxial polydactyly, and variable developmental
      delays. At least 20 genes have been implicated in BBS, and all are involved in
      primary cilia function. We report a 1-year-old male child from Guyana with
      obesity, postaxial polydactyly on his right foot, hypotonia, ophthalmologic
      abnormalities, and developmental delay, which together indicated a clinical
      diagnosis of BBS. Clinical chromosomal microarray (CMA) testing and high
      throughput BBS gene panel sequencing detected a homozygous 7p14.3 deletion of
      exons 1-4 of BBS9 that was encompassed by a 17.5 Mb region of homozygosity at
      chromosome 7p14.2-p21.1. The precise breakpoints of the deletion were delineated
      to a 72.8 kb region in the proband and carrier parents by third-generation long
      read single molecule real-time (SMRT) sequencing (Pacific Biosciences), which
      suggested non-homologous end joining as a likely mechanism of formation. Long
      read SMRT sequencing of the deletion breakpoints also determined that the
      aberration included the neighboring RP9 gene implicated in retinitis pigmentosa;
      however, the clinical significance of this was considered uncertain given the
      paucity of reported cases with unambiguous RP9 mutations. Taken together, our
      study characterized a BBS9 deletion, and the identification of this shared
      haplotype in the parents suggests that this pathogenic aberration may be a BBS
      founder mutation in the Guyanese population. Importantly, this informative case
      also highlights the utility of long-read SMRT sequencing to map nucleotide
      breakpoints of clinically relevant structural variants.

PMID- 29367881
TI  - Changes in zinc-alpha2-glycoprotein (ZAG) plasma concentrations pre and post Roux
      En-Y gastric bypass surgery (RYGB) or a very low calorie (VLCD) diet in
      clinically severe obese patients: Preliminary Study.
AB  - The purpose of this preliminary study was to investigate changes in plasma
      concentrations of zinc-alpha2-glycoprotein (ZAG), a lipid mobilizing hormone, in
      obese subjects following Roux-En-Y Gastric Bypass (RYGB) surgery or a very low
      calorie diet (VLCD). Fasting blood concentrations and anthropometric measurements
      were measured pre and 12 weeks post intervention. 14 healthy, obese individuals
      underwent either RYGB (N=6) surgery or a VLCD (N=8). Body composition and fasting
      plasma ZAG concentrations were measured at baseline (pre) and 12 weeks post
      intervention (post). At pre-intervention baseline, there was no difference in
      plasma ZAG between the two intervention groups. Post-intervention, there was a
      significant overall reduction (F(1,11) = 32.8, p<0.001) in plasma ZAG, which was
      significant only within the RYGB group from pre to post intervention (33.2 +/-
      5.7 MUg/ml to 26.7 +/- 4.8 MUg/ml (p<0.015)) and significantly greater than the
      change within the VLCD group. The change in ZAG was inversely correlated across
      groups with BMI reduction (r= -0.60, p<0.05), % body fat reduction (r= -0.68,
      p<0.015), reduction in weight (r= -0.58, p<0.05), and % weight loss (r= -0.70,
      p<0.05). Overall, subjects who underwent RYGB or VLCD had a significant reduction
      in plasma ZAG. This reduction was significant within the RYGB group alone, who
      lost a larger amount of weight than the VLCD group, which suggests that ZAG may
      have a protective effect during marked weight loss.

PMID- 29367882
TI  - Determinants of postnatal spleen tissue regeneration and organogenesis.
AB  - The spleen is an organ that filters the blood and is responsible for generating
      blood-borne immune responses. It is also an organ with a remarkable capacity to
      regenerate. Techniques for splenic auto-transplantation have emerged to take
      advantage of this characteristic and rebuild spleen tissue in individuals
      undergoing splenectomy. While this procedure has been performed for decades, the
      underlying mechanisms controlling spleen regeneration have remained elusive.
      Insights into secondary lymphoid organogenesis and the roles of stromal organiser
      cells and lymphotoxin signalling in lymph node development have helped reveal
      similar requirements for spleen regeneration. These factors are now considered in
      the regulation of embryonic and postnatal spleen formation, and in the
      establishment of mature white pulp and marginal zone compartments which are
      essential for spleen-mediated immunity. A greater understanding of the cellular
      and molecular mechanisms which control spleen development will assist in the
      design of more precise and efficient tissue grafting methods for spleen
      regeneration on demand. Regeneration of organs which harbour functional white
      pulp tissue will also offer novel opportunities for effective immunotherapy
      against cancer as well as infectious diseases.

PMID- 29367883
TI  - Specific mutations in the D1-D2 linker region of VCP/p97 enhance ATPase activity
      and confer resistance to VCP inhibitors.
AB  - Valosin-containing protein (VCP), together with several partner proteins,
      extracts ubiquitinated client proteins from E3 ligase complex and facilitates
      their degradation through ubiquitin-proteasome system. Therefore, it plays an
      important role in regulating protein quality control and various cellular
      pathways. Recent studies also identified VCP as a lineage-specific essential gene
      in ovarian cancer. An orally bioavailable VCP inhibitor, CB-5083, is currently in
      Phase I clinical trials because it shows therapeutic effects in multiple tumor
      xenograft models. However, the mechanism of resistance to CB-5083 is unknown.
      Here, we characterized molecular mechanism of resistance to CB-5083. Using
      incremental exposure to CB-5083, we established CB-5083-resistant ovarian cancer
      cells that showed five- to six-fold resistance in vitro compared with parental
      cells. Genomic and complementary DNA sequencing of the VCP coding region revealed
      a pattern of co-selected mutations: (1) missense mutations at codon 470 in one
      copy resulting in increased ATPase activity and (2) nonsense or frameshift
      mutations at codon 606 or codon 616 in another copy causing the loss of allele
      specific expression. Unbiased molecular docking studies showed codon 470 as a
      putative binding site for CB-5083. Furthermore, the analysis of somatic mutations
      in cancer genomes from the Cancer Genome Atlas (TCGA) indicated that codon 616
      contains hotspot mutations in VCP. Thus, identification of these mutations
      associated with in vitro resistance to VCP inhibitors may be useful as potential
      theranostic markers while screening for patients to enroll in clinical trials.
      VCP has emerged as a viable therapeutic target for several cancer types, and
      therefore targeting such hyperactive VCP mutants should aid in improving the
      therapeutic outcome in cancer patients.

PMID- 29367884
TI  - Glucose-regulated protein 75 determines ER-mitochondrial coupling and sensitivity
      to oxidative stress in neuronal cells.
AB  - The crosstalk between different organelles allows for the exchange of proteins,
      lipids and ions. Endoplasmic reticulum (ER) and mitochondria are physically
      linked and signal through the mitochondria-associated membrane (MAM) to regulate
      the transfer of Ca2+ from ER stores into the mitochondrial matrix, thereby
      affecting mitochondrial function and intracellular Ca2+ homeostasis. The
      chaperone glucose-regulated protein 75 (GRP75) is a key protein expressed at the
      MAM interface which regulates ER-mitochondrial Ca2+ transfer. Previous studies
      revealed that modulation of GRP75 expression largely affected mitochondrial
      integrity and vulnerability to cell death. In the present study, we show that
      genetic ablation of GRP75, by weakening ER-mitochondrial junctions, provided
      protection against mitochondrial dysfunction and cell death in a model of
      glutamate-induced oxidative stress. Interestingly, GRP75 silencing attenuated
      both cytosolic and mitochondrial Ca2+ overload in conditions of oxidative stress,
      blocked the formation of reactive oxygen species and preserved mitochondrial
      respiration. These data revealed a major role for GRP75 in regulating
      mitochondrial function, Ca2+ and redox homeostasis. In line, GRP75 overexpression
      enhanced oxidative cell death induced by glutamate. Overall, our findings suggest
      weakening ER-mitochondrial connectivity by GRP75 inhibition as a novel protective
      approach in paradigms of oxidative stress in neuronal cells.

PMID- 29367886
TI  - Newborn Survival Case Study in Rwanda - Bottleneck Analysis and Projections in
      Key Maternal and Child Mortality Rates Using Lives Saved Tool (LiST).
AB  - Background and Objective: The Newborn Survival Case study in Rwanda provides an
      analysis of the newborn health and survival situation in the country. It reviews
      evidence-based interventions and coverage levels already implemented in the
      country; identifies key issues and bottlenecks in service delivery and uptake of
      services by community/beneficiaries, and provides key recommendations aimed at
      faster reduction in newborn mortality rate. Methods: This study utilized mixed
      method research including qualitative and quantitative analyses of various
      maternal and newborn health programs implemented in the country. This included
      interviewing key stakeholders at each level, field visits and also interviewing
      beneficiaries for assessment of uptake of services. Monitoring systems such as
      Health Management Information Systems (HMIS), maternal and newborn death audits
      were reviewed and data analyzed to aid these analyses. Results: Policies,
      protocols, various guidelines and tools for monitoring are already in place
      however, implementation of these remains a challenge e.g. infection control
      practices to reduce deaths due to sepsis. Although existing staff are quite
      knowledgeable and are highly motivated, however, shortage of health personnel
      especially doctors in an issue. New facilities are being operationalized e.g. at
      Gisenyi, however, the existing facilities needs expansion. Conclusion and Global
      Health Implications: It is essential to implement high impact evidence based
      interventions but coverage levels need to be significantly high in order to
      achieve higher reduction in newborn mortality rate. Equity approach should be
      considered in planning so that the services are better implemented and the poor
      and needy can get the benefits of public health programs.

PMID- 29367885
TI  - A heterogeneous human immunodeficiency virus-like particle (VLP) formulation
      produced by a novel vector system.
AB  - First identified as the etiological agent behind Acquired Immunodeficiency
      Syndrome (AIDS) in the early 1980s, HIV-1 has continued to spread into a global
      pandemic and major public health concern. Despite the success of antiretroviral
      therapy at reducing HIV-1 viremia and preventing the dramatic CD4+ T-cell
      collapse, infected individuals remain HIV positive for life. Unfortunately, it is
      increasingly clear that natural immunity is not, and may never be, protective
      against this pathogen. Therefore, efficacious vaccine interventions, which can
      either prevent infection or eradicate the latent viral reservoir and effect cure,
      are a major medical priority. Here we describe the development of a safe vaccine
      platform, currently being utilized in on-going prophylactic and therapeutic
      preclinical studies and consisting of highly heterogeneous virus-like particle
      formulations that represent the virus diversity within infected individuals.
      These VLPs contain no 5'LTR, no functional integrase, and have a severely mutated
      stem loop 1-thereby preventing any potential reverse transcription, integration,
      and RNA packaging. Furthermore, we demonstrate that these VLPs are
      morphologically identical to wild-type virus with polyvalent Env in a functional
      form. Finally, we show that the VLPs are antigenic and capable of generating
      strong immune recall responses.

PMID- 29367887
TI  - Determinants of Voluntary HIV/AIDS Counseling and Testing among Community College
      Students in the United States.
AB  - Background: Human Immunodeficiency Virus (HIV) testing remains the best public
      health preventive strategy in the fight against HIV/AIDS. We assessed the factors
      that determined voluntary counseling and screening/testing for HIV among college
      students. Methods: In this cross-sectional study, a purposeful sample of 189
      college students was analyzed using three health belief model (HBM) variables as
      the theoretical framework. Results: All the HBM variables were positively
      associated with intention to test for HIV, and with perceived benefits (p =
      0.023) having the strongest association. Conclusion and Global Health
      Implications: The results of this study underscore the important factors that
      predict intention to screen for HIV among college students. Understanding the
      factors that influence intention for HIV testing is useful in formulating public
      health policies and in the design of programs and interventions aimed at
      increasing the number of people who get tested for HIV.

PMID- 29367888
TI  - Emigration of skilled healthcare workers from developing countries: can team
      based healthcare practice fill the gaps in maternal, newborn and child healthcare
      delivery?
AB  - Background and Introduction: Emigration of healthcare workers from developing
      countries is on the rise and there is an urgent need for policies that increase
      access to and continuity of healthcare. In this commentary, we highlight some of
      the negative impacts of emigration on maternal and child health and discuss
      whether team-based healthcare delivery could possibly mitigate the shortfall of
      maternal and child health professionals in developing countries. Methodology: We
      cross-examine the availability of supporting structures to implement team-based
      maternal and child healthcare delivery in developing countries. We briefly
      discuss three key supporting structures: culture of sharing, telecommunication,
      and inter-professional education. Supporting structures are examined at system,
      organizational and individual levels. We argue that the culture of sharing,
      limited barriers to inter-professional education and increasing access to
      telecommunication will be advantageous to implementing team-based healthcare
      delivery in developing countries. Conclusion and Global Health Implications:
      Although most developing countries may have notable supporting structures to
      implement team-based healthcare delivery, the effectiveness of such models in
      terms of cost, time and infrastructure in resource limited settings is still to
      be evaluated. Hence, we call on usual stakeholders, government, regulatory
      colleges and professional associations in countries with longstanding emigration
      of maternal and child healthcare workers to invest in establishing comprehensive
      models needed to guide the development, implementation and evaluation of team
      based maternal and child healthcare delivery.

PMID- 29367889
TI  - Progresses and challenges of utilizing traditional birth attendants in maternal
      and child health in Nigeria.
AB  - Background and Objectives: Despite advances in modern healthcare, Traditional
      Birth Attendants (TBA) have continued to be heavily utilized in rural communities
      in Nigeria. Major disparities in maternal health care in Nigeria remain present
      despite the goal of the United Nations Millennium Development Goal to reduce
      maternal mortality by 2015. The objective of this study is to review the
      contribution of TBAs in the birthing process in Nigeria, and to examine barriers
      and opportunities for utilizing TBAs in improving maternal and child health
      outcomes in Nigeria. Methods: A literature review of two major electronic
      databases was conducted using the PRISMA framework to identify English language
      studies conducted between 2006 and 2016. Inclusion criteria included articles
      that examined the role of traditional birth attendants as a factor influencing
      maternal health in Nigeria. Results: The value of TBAs has not been fully
      examined as few studies have aimed to examine its potential role in reducing
      maternal mortality with proper training. Eight manuscripts that were examined
      highlighted the role of TBAs in maternal health including outcomes of utilizing
      trained versus non-trained TBAs. Conclusion and Global Health Implications:
      Specific areas of training for TBAs that were identified and recommended in
      review including: recognizing delivery complications, community support for TBA
      practices through policy, evaluation of TBA training programs and increasing
      collaboration between healthcare facilities and TBAs. Policies focused on
      improving access to health services and importantly, formal health education
      training to TBAs, are required to improve maternal health outcomes and
      underserved communities.

PMID- 29367890
TI  - Social Determinants of Health in the United States: Addressing Major Health
      Inequality Trends for the Nation, 1935-2016.
AB  - Objectives: This study describes key population health concepts and examines
      major empirical trends in US health and healthcare inequalities from 1935 to 2016
      according to important social determinants such as race/ethnicity, education,
      income, poverty, area deprivation, unemployment, housing, rural-urban residence,
      and geographic location. Methods: Long-term trend data from the National Vital
      Statistics System, National Health Interview Survey, National Survey of
      Children's Health, American Community Survey, and Behavioral Risk Factor
      Surveillance System were used to examine racial/ethnic, socioeconomic, rural
      urban, and geographic inequalities in health and health care. Life tables, age
      adjusted rates, prevalence, and risk ratios were used to examine health
      differentials, which were tested for statistical significance at the 0.05 level.
      Results: Life expectancy of Americans increased from 69.7 years in 1950 to 78.8
      years in 2015. However, despite the overall improvement, substantial gender and
      racial/ethnic disparities remained. In 2015, life expectancy was highest for
      Asian/Pacific Islanders (87.7 years) and lowest for African-Americans (75.7
      years). Life expectancy was lower in rural areas and varied from 74.5 years for
      men in rural areas to 82.4 years for women in large metro areas, with rural-urban
      disparities increasing during the 1990-2014 time period. Infant mortality rates
      declined dramatically during the past eight decades. However, racial disparities
      widened over time; in 2015, black infants had 2.3 times higher mortality than
      white infants (11.4 vs. 4.9 per 1,000 live births). Infant and child mortality
      was markedly higher in rural areas and poor communities. Black infants and
      children in poor, rural communities had nearly three times higher mortality rate
      compared to those in affluent, rural areas. Racial/ethnic, socioeconomic, and
      geographic disparities were particularly marked in mortality and/or morbidity
      from cardiovascular disease, cancer, diabetes, COPD, HIV/AIDS, homicide,
      psychological distress, hypertension, smoking, obesity, and access to quality
      health care. Conclusions and Global Health Implications: Despite the overall
      health improvement, significant social disparities remain in a number of health
      indicators, most notably in life expectancy and infant mortality. Marked
      disparities in various health outcomes indicate the underlying significance of
      social determinants in disease prevention and health promotion and necessitate
      systematic and continued monitoring of health inequalities according to social
      factors. A multi-sectoral approach is needed to tackle persistent and widening
      health inequalities among Americans.

PMID- 29367891
TI  - Intrasession Repeatability and Interocular Symmetry of Foveal Avascular Zone and
      Retinal Vessel Density in OCT Angiography.
AB  - Purpose: To measure intrasession repeatability and interocular symmetry of the
      foveal avascular zone area (FAZA) and superficial retinal vessel density (SRVD)
      using AngioVue Analytics optical coherence tomography angiography (OCTA).
      Methods: Fifty healthy individuals were prospectively enrolled. OCTA scans (3 * 3
      and 6 * 6 mm) were acquired twice in right and once in left eyes. FAZA (with and
      without rescaling) and SRVD for 18 regions (whole, fovea, parafovea, six
      parafoveal subregions, and nine square zones) were compared between two scans in
      right eyes (repeatability) and between both eyes (symmetry). Coefficients of
      repeatability (CRs) and limits of agreement (LAs) were calculated. Results: Axial
      length-based image size rescaling had negligible impact on the intrasession CR of
      FAZA in both 3 * 3- and 6 * 6-mm images. The intrasession CRs for the foveal SRVD
      were 3.3% and 6.1% in the 3 * 3- and 6 * 6-mm OCTA images, respectively. Age and
      axial length did not influence test-retest variability of FAZA or SRVD. The
      interocular LAs in FAZA (0.039-0.059 mm2) was comparable to its CR. However, the
      interocular LAs in foveal SRVD were -4.5% to +3.8%, with 13% of the cohort
      showing an interocular difference greater than the CR. Conclusions: FAZA
      repeatability is not influenced by image size correction, and foveal SRVD is more
      variable in 6 * 6- than 3 * 3-mm OCTA images. Low image quality may contribute to
      interocular SRVD asymmetry. Translational Relevance: CRs and LAs can be used to
      set a threshold for true changes in FAZA and SRVD in longitudinal studies of
      healthy individuals.

PMID- 29367893
TI  - Three Dimensional Stimulus Source for Pattern Electroretinography in Mid- and Far
      peripheral Retina.
AB  - Purpose: The pattern electroretinogram (pERG) response reflects, in part,
      ganglion cell function. However, probing retinal ganglion cell (RGC) function in
      the mid- and far peripheral retina is difficult with conventional flat-panel pERG
      stimulus sources. A pattern stimulus source is presented for probing the
      peripheral retina. Peripheral pERG (ppERG) responses were evaluated versus
      luminance, reversal rate, and field subtended, and were compared with
      conventional pERG in healthy eyes. Methods: Eleven normally-sighted subjects were
      recruited. A hemispherical surface was used to present a reversing checkerboard
      pattern to the peripheral retina, from approximately 35 degrees  to 85 degrees 
      of visual field, in all directions. Responses to stimuli presented to peripheral
      field sectors (superior, nasal, inferior, temporal) were also recorded.
      Conventional pERG responses were recorded on the same day. Amplitudes and
      implicit times of waveform peaks were evaluated. Results: Robust pERG responses
      from peripheral retina resemble conventional pERG responses but with shorter
      implicit times and reduced positive component. Responses to high-luminance
      patterns include high-frequency components resembling flash ERG oscillatory
      potentials. Negative response component amplitudes increased with increasing
      pattern luminance, and decreased with increasing reversal rate. Conclusions:
      Peripheral-field pERG responses are robust and repeatable; the unique response
      properties reflect differences between central and peripheral retina. Field
      sector response ratios can be used to probe for sectoral dysfunction associated
      with disease. Translational Relevance: The ppERG approach provides direct
      measurement of proximal retinal function beyond the fields probed by conventional
      perimetry and pERG, providing access to a relatively under studied part of the
      retina relevant to early stage glaucoma.

PMID- 29367892
TI  - The Magnetic Levator Prosthesis for Temporary Management of Severe
      Blepharoptosis: Initial Safety and Efficacy.
AB  - Purpose: We further optimized and evaluated the safety of the magnetic levator
      prosthesis (MLP) for temporary management of severe blepharoptosis, and compared
      efficacy and comfort against the ptosis crutch. Methods: The interpalpebral
      fissure (IPF) of participants (n = 12) with ptosis was measured during attempted
      eyelid opening, volitional closing, and spontaneous closing with no device,
      ptosis crutch, or the MLP. A 10-point scale documented comfort. Additionally, a
      20 minute and then 1 week trial of the MLP was offered. Safety measures were skin
      erythema rating, change in visual acuity, and change in corneal staining.
      Results: The MLP and crutch opened the eye (IPF 11.2 and 9.3 mm), but the MLP
      allowed better volitional closure (IPF 1.0 vs. 4.9 mm, P = 0.009), but was no
      better in allowing spontaneous blink (IPF 7.5 vs. 7.7 mm, P = 0.722). Both
      devices were equally comfortable (both median 8/10 comfort, P = 0.46). With
      extended use, opening with the MLP showed IPF 9.24 mm at 20 minutes and 9.46 mm
      at 1 week, and volitional closure was IPF 0.95 and 0.52 mm, respectively. Closure
      on spontaneous blink improved with extended wear to IPF 5.14 and 5.18 mm,
      respectively (P = 0.002). Two participants exhibited moderate skin erythema and
      one had increased corneal staining without change in acuity. Conclusions: The MLP
      is safe and feasible for temporary correction of severe ptosis. Translational
      Relevance: First group data in patients showing successful reanimation of the
      eyelid with magnetic force.

PMID- 29367894
TI  - A Functional Regression Model of the Retinal Nerve Fiber Layer Thickness in
      Healthy Subjects.
AB  - Purpose: A new functional regression model is presented to explain the
      intersubject variability of the circumpapillary retinal nerve fiber layer (RNFL)
      thickness in healthy subjects. Methods: To evaluate the functional regression
      approach we used data from 202 healthy volunteers, divided equally into training
      samples (TS) and validation samples (VS). Covariates included RNFL, fovea
      distance, fovea angle, optic disk ratio, orientation and area provided by Fourier
      domain-optical coherence tomography, age, and refractive error. Root mean square
      errors (RMSE) were calculated for each of the 256 sectors and for the 12 clock
      hour sectors in the TS and VS and were compared to the RMSE of the previous model
      and the standard deviation of the raw data. Results: With the functional
      regression approach, we were able to explain on average 27.4% of the variation in
      the TS and 25.1% of the variation in the VS. The new model performed better
      compared to a multivariate linear regression model. It performed best in the
      superior-temporal and inferior-temporal clock-hour sectors where the percentage
      of RMSE reduction ranged between 26.3% and 44.1% for the TS and between 20.6% and
      35.4% for the VS. Conclusions: The new functional regression approach improves on
      the multivariate linear regression model and allows an even larger reduction of
      the amount of intersubject variability, while at the same time using a
      substantially smaller number of parameters to be estimated. Translational
      Relevance: The demonstrated reduction of interindividual variation is expected to
      translate into an improved diagnostic separation between healthy and glaucomatous
      subjects, but this remains to be demonstrated in further studies.

PMID- 29367895
TI  - Correlates of weekday compliance to physical activity recommendations in Swiss
      youth non-compliant in weekend days.
AB  - Some children are inactive on weekends but active on weekdays. Correlates of such
      behavior remain to be clarified. We assessed school, out-of-school and family
      correlates of compliance with physical activity (PA) recommendations during
      weekdays among weekend non-compliant youth in Switzerland. Cross-sectional data
      collected in 2013-2015 from the SOPHYA study. PA was objectively measured during
      one week using waist-worn accelerometers. Compliance with PA recommendations (>=
      60 min/day of moderate-to-vigorous PA) was assessed separately for weekend and
      weekdays. Data on school sport, transport to school, sports club participation,
      household income, parent's PA and education were collected by phone interview and
      questionnaires. Data from 540 youth (316 girls) aged 6-16 years were available
      for analysis. Participants who were compliant to recommendations during weekdays
      were more frequently boys (50.3% vs. 31.4%, p < 0.001), more often participated
      in sports club (73.3% vs. 64.3%, p = 0.024), and were more prone to adopt active
      transport to school (75.8% vs. 62.0%, p = 0.001) than non-compliers.
      Multivariable adjustment showed male gender [odds ratio and (95% confidence
      interval): 4.30 (2.71-6.81)], sports club participation [1.91 (1.21-3.02)], and
      PA-active parent [1.98 (1.20-3.28)] were significantly associated with weekday
      compliance. Being a male, a sports club participant and having a physically
      active parent significantly increase compliance with PA recommendations during
      weekdays among Swiss youth who are inactive on weekends.

PMID- 29367896
TI  - Pleomorphic undifferentiated sarcoma: A case of a giant renal mass.

PMID- 29367897
TI  - Non-traumatic testicular rupture following episode of epididymo-orchitis.

PMID- 29367898
TI  - RBO in a new era.

PMID- 29367899
TI  - Evaluation of interobserver agreement in Albertoni's classification for mallet
      finger.
AB  - Objective: To measure the reliability of Albertoni's classification for mallet
      finger. Methods: Agreement study. Forty-three radiographs of patients with mallet
      finger were assessed by 19 responders (12 hand surgeons and seven residents).
      Injuries were classified by Albertoni's classification. For agreement comparison,
      lesions were grouped as: (A) tendon avulsion; (B) avulsion fracture; (C) fracture
      of the dorsal lip; and (D) physis injury-and subgroups (each group divided into
      two subgroups). Agreement was assessed by Fleiss's modification for kappa
      statistics. Results: Agreement was excellent for Group A (k = 0.95 (0.93-0.97))
      and remained good when separated into A1 and A2. Group B was moderate (k = 0.42
      (0.39-0.44)) and poor when separated into B1 and B2. In the Group C, agreement
      was good (k = 0.72 (0.70-0.74)), but when separated into C1 and C2, it became
      moderate. Group D was always poor (k = 0.16 (0.14-0.19)). The general agreement
      was moderate, with (k = 0.57 (0.56-0.58)). Conclusion: Albertoni's classification
      evaluated for interobserver agreement is considered a reproducible classification
      by the method used in the research.

PMID- 29367900
TI  - Epidemiological analysis of patients with Dupuytren's disease.
AB  - Objective: To evaluate the risk factors and analyze the characteristics of
      patients and lesions in Dupuytren's disease. Methods: Retrospective analysis of
      patients diagnosed with Dupuytren's disease in a hand surgery clinic in 2013. The
      authors evaluated parameters associated with the patient profiles and risk
      factors, the form and severity of involvement, and characteristics of the
      lesions. Results: 58 patients were evaluated, totaling 79 hands, with bilateral
      involvement in 46% of cases. The involvement of the ulnar fingers of the hand
      represented 78%, 44% being the ring finger. In 55% of cases, the patients had
      cords, while 45% showed only nodules. As for related factors, they were found
      most commonly in men (55%), whites (93%), and the elderly. Of coexisting
      diseases, the following were present: diabetes mellitus (49%), especially in the
      insulin-dependent (62%), hypertension (55.2%), and dyslipidemia (19%). With
      regard to lifestyle, 22% were smokers and 9% were alcohol consumers. Conclusion:
      It was observed a higher incidence of Dupuytren's disease was observed among men,
      whites, and the ulnar fingers of the hand, especially the ring finger. The most
      common associated diseases were diabetes mellitus and hypertension.

PMID- 29367901
TI  - Axillary nerve neurotization by a triceps motor branch: comparison between
      axillary and posterior arm approaches.
AB  - Objectives: This study is aimed at comparing the functional outcome of axillary
      nerve neurotization by a triceps motor branch through the axillary approach and
      posterior arm approach. Methods: The study included 27 patients with post
      traumatic brachial plexus injury treated with axillary nerve neurotization by a
      triceps motor branch for functional recovery of shoulder abduction and external
      rotation. The patients were retrospectively evaluated and two groups were
      identified, one with 13 patients undergoing axillary nerve neurotization by an
      axillary approach and the second with 14 patients using the posterior arm
      approach. Patients underwent assessment of muscle strength using the scale
      recommended by the British Medical Research Council, preoperatively and 18 months
      postoperatively, with useful function recovery considered as grade M3 or greater.
      Results: In the axillary approach group, 76.9% of patients achieved useful
      abduction function recovery and 69.2% achieved useful external rotation function
      recovery. In the group with posterior arm approach, 71.4% of patients achieved
      useful abduction function recovery and 50% achieved useful external rotation
      function recovery. The difference between the two groups was not statistically
      significant (p = 1.000 for the British Medical Research Council abduction scale
      and p = 0.440 for external rotation). Conclusion: According to the British
      Medical Research Council grading, axillary nerve neurotization with a triceps
      motor branch using axillary approach or posterior arm approach shows no
      statistical differences.

PMID- 29367902
TI  - Venous thromboembolism prophylaxis after total knee arthroplasty (TKA): aspirin
      vs. rivaroxaban.
AB  - Objectives: To compare the efficacy and safety of aspirin and rivaroxaban in
      preventing venous thromboembolism (VTE) after total knee arthroplasty (TKA).
      Methods: Thirty-two patients with osteoarthritis of the knee and knee
      arthroplasty indication were selected. The operated patients were randomized into
      two groups (A and B). Group A received 300 mg of acetylsalicylic acid (aspirin)
      and Group B received 10 mg of rivaroxaban daily for 14 days. Follow-up was
      performed weekly for four weeks and evaluated the presence of signs and symptoms
      of DVT, the healing of the surgical wound, and possible local complications such
      as hematoma, and superficial or deep infection that required surgical approach.
      Results: It was verified that there were no differences between groups
      (rivaroxaban and aspirin) regarding gender, age, and (p > 0.05). After using the
      general linear model (GLM) test, it was found that there was a decrease in Hb and
      Ht levels, preoperatively and at one, three, seven, and 14 days (Hb: p = 1.334 *
      10-30; Ht: p = 1.362 * 10-28). However, they did not differ as to the type of
      medication (Hb: p = 0.152; Ht: p = 0.661). There were no identifiable differences
      in local complications, systemic complications, deep vein thrombosis (DVT),
      readmission to hospital, reoperation, or death (p > 0.05) between groups
      (rivaroxaban and aspirin). Conclusions: Both aspirin and rivaroxaban can be
      considered useful among drugs available VTE the prevention after TKA.

PMID- 29367903
TI  - Use of MRI by radiologists and orthopaedic surgeons to detect intra-articular
      injuries of the knee.
AB  - Objective: Magnetic resonance imaging (MRI) is paramount in the assessment of
      knee pathology, particularly when planning for a surgical procedure. This study
      compared the diagnostic accuracy in MRI reading of pathological knees by
      radiologists and orthopaedic surgeons. Materials and methods: Cross-sectional
      study comprising 80 randomly selected patients previously submitted to
      arthroscopic surgery after clinical examination and MRI. A diagnosis by MRI
      interpretation was requested from the two teams, one of radiologists and another
      of orthopaedic surgeons. The conclusions of each team were later compared.
      Statistical significance was considered for p < 0.05. Results: The radiologists'
      findings achieved statistical significance regarding osteochondral injuries, ACL,
      and medial meniscus (p < 0.05), and orthopaedic surgeons regarding ACL injuries
      and menisci (p < 0.05). ACL injuries demonstrated a statistically significant
      association between teams (p < 0.001). Conclusions: MRI appears to offer reliable
      readings of ACL injuries, regardless the specialty of the observer. The lateral
      compartment is scarcely well read.

PMID- 29367904
TI  - Epidemiological characteristics of patients with pelvic tumors submitted to
      surgical treatment.
AB  - Objective: Describe the epidemiological profile of patients with primary or
      secondary neoplastic lesions in the pelvis who required a surgical procedure such
      as hemipelvectomy. Methods: This study retrospectively evaluated 69 patients
      located in the database of a Sao Paulo educational institution, subject to
      surgical hemipelvectomy treatment between January 1990 and December 2013. All
      patients had previous diagnosis of bone tumor (primary or metastatic) in the
      pelvis (ilium, ischium, pubis, and/or sacrum). Results: Analyzing the data
      obtained in this study, it was observed that these are partly similar to those
      found in the literature, with primary bone malignancies as the main diagnosis;
      general injuries affecting the pelvic area I (pelvic bone) and its most frequent
      complication, infection. The differences are mainly due to rarity of the bone
      tumors evaluated in this study, and the type of surgical procedure in question,
      which is even more unusual. Conclusion: Building a picture that conveys the
      reality of each diagnosis and that indicates which characteristics of these
      patients would better resemble an absolute or relative indication for the
      realization of hemipelvectomy is harder by the rarity of these cases.

PMID- 29367905
TI  - Influence of anxiety and depression symptoms on the quality of life in patients
      undergoing lumbar spine surgery.
AB  - Objective: Comparative analysis of the quality of life and functionality of
      patients undergoing lumbar spine arthrodesis due to degenerative lumbar spine
      disease. The authors sought to correlate the influence of anxious and depressive
      symptoms before and after surgery. Methods: A prospective cohort study was
      performed, with 32 patients submitted to arthrodesis due to degenerative lumbar
      spine disease and the visual analogue pain scale pain questionnaire, the Oswestry
      Disability Index questionnaire, the Medical Outcomes Survey Short Form
      questionnaire - 36 items (SF-36), and the Hospital Anxiety and Depression Scale,
      applied in the preoperative period and four months after the procedure. Results:
      There was improvement in the mean scores of the visual analogue pain scale (p <
      0.001) and the Oswestry Disability Index (p < 0.001). In the preoperative period,
      the variables that presented a difference between patients with and without
      anxiety symptoms were the SF-36 domains of general health (p = 0.031), social
      aspects (p = 0.008), and mental health (p = 0.035). In the postoperative period,
      patients without anxiety symptoms showed better results in the vitality (p =
      0.004), social aspects (p = 0.001), mental health (p < 0.001), and pain (p =
      0.011) domains. In the preoperative period, the variable that presented a
      difference between patients with and without depression was the SF-36 domain of
      emotional aspects (p = 0.022). In the post-operative period, patients without
      depression presented better vitality (p < 0.001), social aspects (p < 0.001),
      emotional aspects (p = 0.004), and mental health results (p = 0.001). Conclusion:
      Lumbar spine arthrodesis was effective in improving pain, low back pain,
      functional capacity, limitation due to physical aspects, vitality, and social and
      emotional aspects. Patients without anxiety and depression symptoms had better
      results on the scales compared to those with such symptoms.

PMID- 29367906
TI  - Proliferation and differentiation of stem cells in contact with eluate from
      fibrin-rich plasma membrane.
AB  - Objective: To evaluate the ability of the eluate from fibrin-rich plasma (FRP)
      membrane to induce proliferation and differentiation of isolated human adipose
      derived stem cells (ASCs) into chondrocytes. Method: FRP membranes were obtained
      by centrifugation of peripheral blood from two healthy donors, cut, and
      maintained in culture plate wells for 48 h to prepare the fibrin eluate. The
      SCATh were isolated from adipose tissue by collagenase digestion solution, and
      expanded in vitro. Cells were expanded and treated with DMEM-F12 culture, a
      commercial media for chondrogenic differentiation, and eluate from FRP membrane
      for three days, and labeled with BrdU for quantitative assessment of cell
      proliferation using the High-Content Operetta(r) imaging system. For the
      chondrogenic differentiation assay, the SCATh were grown in micromass for 21 days
      and stained with toluidine blue and aggrecan for qualitative evaluation by light
      microscopy. The statistical analysis was performed using ANOVA and Tukey's test.
      Results: There was a greater proliferation of cells treated with the eluate from
      FRP membrane compared to the other two treatments, where the ANOVA test showed
      significance (p < 0.001). The differentiation into chondrocytes was visualized by
      the presence of mucopolysaccharide in the matrix of the cells marked in blue
      toluidine and aggrecan. Conclusions: Treatment with eluate from FRP membrane
      stimulated cell proliferation and induced differentiation of the stem cells into
      chondrocytes, suggesting a potential application of FRP membranes in hyaline
      cartilage regeneration therapies.

PMID- 29367907
TI  - The effects of ethyl-2-cyanoacrylate and butyl-2-cyanoacrylate in the process of
      bone healing in rats. A controlled experimental study.
AB  - Objective: Synthetic adhesives are used by various medical specialties,
      especially in surgery; however, studies reporting their use in orthopedic
      practice are scarce. The aim of this study was to compare the results in using
      ethyl-2-cyanoacrylate or butyl-2-cyanoacrylate in the treatment of fractures in
      rats. Methods: This was an experimental prospective controlled study in 90 rats,
      with humerus, femur, and tibia fractures, treated with ethyl-2-cyanoacrylate (SB
      group; n = 45) or butyl-2-cyanoacrylate (HA group; n = 45). Biomechanical and
      histomorphometric analyses were performed at three different moments (60, 120,
      and 180 days); besides a clinical study performed weekly by measurement of the
      animals body mass. Results: No differences were observed regarding body mass (p =
      0.07). In both groups, there were no significant differences regarding maximum
      load (p = 0.6), yield point strength (p = 0.6), and stiffness coefficient (p =
      0.4) of the femurs. The same was observed in tibias for maximum load (p = 0.4),
      yield point strength (p = 0.7), and stiffness coefficient (p = 0.6). The humerus
      from both groups had similar bone callus area (p = 0.66). In both groups, there
      were no statistical differences related to inflammatory cells (p = 0.4),
      osteoblasts (p = 0.2), and osteoclasts (p = 0.2). Conclusion: Ethyl-2
      cyanoacrylate was more effective than butyl-2-cyanoacrylate in the treatment of
      fractures in rats.

PMID- 29367908
TI  - Surgical treatment of pectoralis major muscle rupture with adjustable cortical
      button.
AB  - Objective: To assess the tendon reconstruction technique for total rupture of the
      pectoralis major muscle using an adjustable cortical button. Methods: Prospective
      study of 27 male patients with a mean age of 29.9 (SD = 5.3 years) and follow-up
      of 2.3 years. The procedure consisted of autologous grafts taken from the
      semitendinosus and gracilis tendons and an adjustable cortical button. Patients
      were evaluated functionally by the Bak criteria. Results: The surgical treatment
      of pectoralis major muscle tendon reconstruction was performed in the early
      stages (three weeks) in six patients (22.2%) and in 21 patients (77.8%), in the
      late stages. Patients operated with the adjustable cortical button technique
      obtained 96.3% excellent or good results, with only 3.7% having poor results (Bak
      criteria). Of the total, 85.2% were injured while performing bench press
      exercises and 14.8%, during the practice of Brazilian jiu-jitsu or wrestling. All
      weight-lifting athletes had history of anabolic steroid use. Conclusion: The
      early or delayed reconstruction of ruptured pectoralis major muscle tendons with
      considerable muscle retraction, using an adjustable cortical button and
      autologous knee flexor grafts, showed a high rate of good results.

PMID- 29367909
TI  - A combined technique for acromioclavicular reconstruction after acute dislocation
      - technical description and functional outcomes.
AB  - Objective: This study aims to describe the surgical approach to such injuries and
      to present the clinical and functional outcomes obtained in a cohort of patients.
      Methods: This is an observational retrospective study that included 153 patients
      with acute acromioclavicular joint dislocation, operated between 1999 and 2015.
      Clinical evaluation included the following outcomes: Constant functional scale,
      development of complications, time to return to previous work/sport activities,
      and satisfaction index. The contra-lateral (uninjured) shoulder was used as
      control in subjective outcomes. Radiological evaluation was performed in order to
      monitor signs of loss of reduction, degenerative joint changes, and
      coracoclavicular calcifications. Results: The mean age was 29.20 +/- 9.53 (16
      71), with a large male predominance (91.5%). Follow-up lasted 55.41 +/- 24.87 (12
      108) months. The mean Constant score attained was 96.45 +/- 4.00 (84-100) on
      operated shoulders and 98.28 +/- 1.81 (93-100) on contralateral ones. Almost all
      patients (98.69%) were satisfied with the surgical results. Worse outcomes were
      observed in acromioclavicular joint dislocations of increasing grade (from type
      III to V, but worse for type IV), both concerning the Constant score and return
      to work or sport. The overall incidence of complications was considered low, with
      the most prevalent being Kirschner wire failure and isolated coracoclavicular
      ligament calcifications. Conclusion: The surgical technique described is an
      excellent option in the treatment of acute acromioclavicular joint dislocations
      of Rockwood grades III to V. This is corroborated by the excellent clinical and
      functional outcomes and the low rate of complications.

PMID- 29367910
TI  - Bicipital aponeurosis. Anatomical study and clinical implications.
AB  - Objective: The aim of this study was to analyze the anatomic variations of the
      bicipital aponeurosis (BA) (lacertus fibrosus) and its implications for the
      compression of the median nerve, which is positioned medially to the brachial
      artery, passing under the bicipital aponeurosis. Methods: Sixty upper limbs of 30
      cadavers were dissected, 26 of which were male and four, female; of the total, 15
      had been previously preserved in formalin and glycerine and 15 were dissected
      fresh in the Laboratory of Anatomy. Results: In 55 limbs, short and long heads of
      the biceps muscle contributed to the formation of the BA, and the most
      significant contribution was always from the short head. In three limbs, only the
      short head contributed to the formation of the BA. In two limbs, the BA was
      absent. The length of the bicipital aponeurosis from its origin to its insertion
      ranged from 4.5 to 6.2 cm and its width, from 0.5 to 2.6 cm. In 42 limbs, the BA
      was thickened; of these, in 27 it was resting directly on the median nerve, and
      in 17 a high insertion of the humeral head of the pronator teres muscle was
      found, and the muscle was interposed between the BA and the median nerve.
      Conclusion: These results suggest that a thickened BA may be a potential factor
      for nerve compression, by narrowing the space through which the median nerve
      passes.

PMID- 29367911
TI  - Treatment of displaced femoral neck fractures in young patients with DHS and its
      association to osteonecrosis.
AB  - Objective: The purpose of this study is to evaluate the performance of dynamic
      hip screw for the treatment of dislocated femoral neck fractures in young
      patients, focusing on osteonecrosis. Methods: A series of 53 patients with less
      than 55 years of age were retrospectively evaluated. All patients had dislocated
      femoral neck fractures (Garden III or IV) and were treated with DHS. Ficat's
      staging system was used to evaluate avascular necrosis. Results: There were 38
      (71.7%) males and 15 (28.3%) females, with an overall mean age at the onset of
      fracture of 41.9 years (+/-12.8). According to Garden's classification, 21
      (39.6%) fractures were classified as type III and 32 (60.4%) were considered
      totally dislocated, Garden IV. Fracture healing was achieved in 39 patients
      (73.6%). Thirteen cases of avascular necrosis were observed (24.6%). Conclusions:
      The incidence of avascular necrosis in young patients with a displaced femoral
      neck fractures treated with DHS was 24.6%. No statistically significant
      association was found between times elapsed to surgery, fracture displacement,
      and presence of derotation screw with osteonecrosis. Level of evidence IV.

PMID- 29367912
TI  - Mind the gap between the fracture line and the length of the working area: a 2-D
      finite element analysis using an extramedullary fixation model.
AB  - Objective: To determine the ideal working area for a simple transverse fracture
      line treated with a bridge plate. Methods: A 2-D finite element analysis of a
      hypothetical femur was performed for the quantitative evaluation of a large
      fragment titanium alloy locking plate based on the precept of relative stability
      in a case of a simple transverse diaphyseal fracture. Two simulations (one case
      of strain and another case of stress distribution) were analyzed in three unique
      situations according to the von Mises stress theory. Load distributions were
      observed when the bone was subjected to a single vertical load of 1000 N.
      Results: The longer the length of the implant flexion, which coincided with the
      working area of the plate, the greater the flexion of the implant. The highest
      concentrations of stress on the plate occurred in the region around the screws
      closest to the bone gap. The closer the screws to the fracture site, the greater
      the demands on the plate. Conclusion: When using a large-fragment titanium alloy
      locking plate to stabilize a simple transverse fracture based on the precept of
      relative stability (bridge plate), there must be considerable distance between
      the proximal and distal screws closest to the fracture line. The farther away
      this fixation is, the lower the stress on the plate and the greater the
      dissipation of force in the form of deflection.

PMID- 29367913
TI  - Radiographic evaluation of 19 patients with Paprosky 3A and 3B submitted to
      acetabular review with trabecular metal wedge.
AB  - Objective: This study is aimed at evaluating the fixation of trabecular metal
      wedges in patients who underwent revision of total hip arthroplasty with large
      acetabular bone defects. Methods: The radiographs of 19 patients (21 hips), who
      underwent revision of total hip arthroplasty using trabecular metal wedges from
      September 2010 to December 2014 were evaluated. This study included only cases of
      Paprosky 3A and 3B. Preoperative and postoperative images were analyzed. Non
      fixation of the implant was defined by the presence of angular variation of the
      component higher 10 degrees or displacement greater than 6 mm. Patients with
      follow-up times of less than 24 months or who did not attend the last two
      appointments were excluded from the study. Results: The mean follow-up time was
      39.4 months (25-61). Fixation was achieved in all cases despite its complexity.
      There was only one case of dislocation that was treated with open reduction. One
      case developed infection, and was surgically approached on two occasions, with
      extensive debridement and intravenous antibiotics following protocol, with good
      evolution. Conclusion: The implanted trabecular metal wedges showed excellent
      results in the short- and medium-term and may represent another option in the
      reconstruction of large acetabular defects, sometimes replacing bone
      reconstruction that uses bone tissue banks or autologous graft.

PMID- 29367914
TI  - Reproducibility of the Lauge-Hansen, Danis-Weber, and AO classifications for
      ankle fractures.
AB  - Objective: This study evaluated the reproducibility of the three main
      classifications of ankle fractures most commonly used in emergency clinical
      practice: Lauge-Hansen, Danis-Weber, and AO-OTA. The secondary objective was to
      assess whether the level of professional experience influenced the interobserver
      agreement for the classification of this pathology. Methods: The study included
      83 digitized preoperative radiographic images of ankle fractures, in
      anteroposterior and lateral views, of different adults that had occurred between
      January and December 2013. For sample calculation, the estimated accuracy was
      approximately 15%, with a sampling error of 5% and a sampling power of 80%. The
      images were analyzed and classified by six different observers: two foot and
      ankle surgeons, two general orthopedic surgeons, and two-second-year residents in
      orthopedics and traumatology. The Kappa statistical method of multiple variances
      was used to assess the variations. Results: The Danis-Weber classification
      indicated that 40% of the agreements among all observers were good or excellent,
      whereas only 20% of good and excellent agreements were obtained using the AO and
      Lauge Hansen classifications. The Kappa index was 0.49 for the Danis-Weber
      classification, 0.32 for Lauge Hansen, and 0.38 for AO. Conclusion: The Hansen
      Lauge classification presented the poorest interobserver agreement among the
      three systems. The AO classification demonstrated a moderate agreement and the
      Danis-Weber classification presented an excellent interobserver agreement index,
      regardless of professional experience.

PMID- 29367915
TI  - Epidemiology of cauda equina syndrome. What changed until 2015.
AB  - Objective: The primary objective of this study was to analyze the characteristics
      and outcomes of cases admitted to hospital with cauda equina syndrome (CES) at
      the Institute of Orthopedics and Traumatology (IOT) from 2005 to 2015. Secondly,
      this article is a continuation of the epidemiological work of the same base
      published in 2013, and will be important for other comparative studies to a
      greater understanding of the disease and its epidemiology. Methods: This was a
      retrospective study of the medical records of admissions due to CES at IOT in the
      period 2005-2015 with diagnosis of CES and neuropathic bladder. The following
      variables were analyzed: gender, age, etiology of the disease, topographic level
      of the injury, time interval between injury and diagnosis, presence of neurogenic
      bladder, time interval between diagnosis of the CES and surgery, and reversal of
      the deficit or of the neurogenic bladder. Results: Since this is a rare disease,
      with a low global incidence, it was not possible, just with the current study to
      establish statistically significant correlations between the variables and
      outcomes of the disease. However, this study demonstrates the shortcomings of the
      Brazilian public health system, both with the initial management of these
      patients and the need for urgent surgical treatment. Conclusion: The study shows
      that despite well-defined basis for the conduct of CES, a higher number of
      sequelae caused by the pathology is observed in Brazil. The delay in diagnosis
      and, therefore, for definitive treatment, remains as the major cause for the high
      number of sequelae. Level of evidence: 4, case series.

PMID- 29367916
TI  - Articular reconstruction of the humeral head with autogenous allograft in the
      treatment of the osteonecrosis.
AB  - The authors describe a surgical biological reconstruction of the humeral head
      with frozen autogenous allograft technique for the treatment of young patients
      with focal osteonecrosis of the humeral head. This represents a possible
      alternative, maybe even definitive for some patients, when compared to
      hemiarthroplasty or total shoulder arthroplasty. The technique consists of the
      fixation of a frozen autogenous allograft with previously-molded articular
      cartilage from the humeral head, after cleansing the osteonecrotic focus. Five
      patients under 50 years of age were treated, with three very satisfactory
      results, one patient was lost to follow-up, and one patient had an unsatisfactory
      result (converted to hemiarthroplasty). The study describes the technique in
      detail and the three cases with a longer follow-up time.

PMID- 29367917
TI  - Update on open reduction and internal fixation of unstable pelvic fractures
      during pregnancy: case reports.
AB  - : This article aims to report four cases of unstable pelvic fractures in pregnant
      women treated by open reduction and internal fixation. Cases report: The study
      included four cases of pregnant women with unstable pelvic fractures; their
      outcomes were analyzed and discussed. Data were obtained from two University
      Hospitals. The mean age of women was 23 years; most (3/4) were primiparous, with
      a mean pregnancy age of 23 weeks. Two women had Malgaigne-type fractures and the
      other two had symphyseal disjunction associated with acetabular fractures. All
      fractures were treated surgically. One foetus was dead on admission to hospital.
      The other three developed well, along with their mothers. Good evolution was only
      possible with careful pre-, peri-, and postoperative care for the mother, as well
      as foetal assessment by a multidisciplinary team. In complex cases such as those
      presented in the present study, pre-, peri-, and postoperative care are
      mandatory, as well as the presence of a multidisciplinary team. The mother's life
      always takes priority in acute clinical pictures, as it offers the best chance of
      survival to both mother and child.

PMID- 29367918
TI  - Femoral pseudoaneurysm as a complication of slipped capital femoral epiphysis
      treatment.
AB  - Slipped capital femoral epiphysis is a very frequently seen condition in
      orthopedics centers worldwide. Even in successfully treated cases, complications
      related either with the pathology per se or with the chosen synthesis method are
      not rare. This report presents a case of bilateral slipped capital femoral
      epiphysis treated with pinning, in which one of the limbs developed a very rare
      condition: the formation of a femoral pseudoaneurysm that ruptured.

PMID- 29367921
TI  - Revalidation of Synonymy between Nesotriatoma flavida and N. bruneri (Hemiptera,
      Reduviidae, Triatominae).
AB  - Background: We analyzed the external morphology and the external male genitalia
      of specimens of Nesotriatoma flavida of a laboratory colony founded with
      specimens from Guanahacabiles in Pinar del Rio Province in the west of Cuba in
      1980. This species was at first identified as different from N. bruneri and then
      later considered synonymous. Methods: We proposed to revise the morphological
      characters with which these species were considered as different and then later
      synonymous, such as the fossula spongiosa or spongy grooves, length of the first
      antenna segment, relationship length of eye to interocular distance, the form of
      the phallosome, phallosome support, and the endosome processes. Results: The
      results of the analyses of these characters in the specimens of our colony, and
      of the corresponding works where the separation and synonymy of these species has
      been proposed, allow us to sustain the revalidation of the synonymy between N.
      flavida and N. bruneri. Conclusion: Based on the body external morphology and the
      male external genitalia of N. flavida it is concluded that N. flavida and N.
      bruneri are synonymous species.

PMID- 29367920
TI  - The pronounced high expression of discoidin domain receptor 2 in human
      interstitial lung diseases.
AB  - The most typical structural feature of human interstitial lung diseases (ILDs) is
      the accumulation of vast amounts of collagens within the lung interstitium. The
      membrane receptors that are responsible for recognising collagens and then
      transducing signals into the cells include four members of the integrin family
      (alpha1beta1, alpha2beta1, alpha10beta1 and alpha11beta1) and two members of the
      discoidin domain receptor family (DDR1 and DDR2). However, it remains unknown
      whether these six collagen receptors similarly contribute to the pathogenesis of
      fibrotic lung diseases. Quantitative real-time PCR (qPCR) was utilised to assess
      the mRNA expression of the genes studied. Immunoblot experiments were performed
      to analyse the protein abundance and kinase activity of the gene products. The
      tissue location was determined by immunohistochemical staining. qPCR data showed
      that DDR2 mRNA displays the most dramatic difference between idiopathic pulmonary
      fibrosis (IPF) patients and healthy groups. The outstanding increases in DDR2
      proteins were also observed in some other types of ILD besides IPF. DDR2
      expressing cells in ILD tissue sections were found to exhibit spindle or
      fibroblastic shapes. Our investigation suggests that DDR2 might represent a major
      cell surface protein that mediates collagen-induced cellular effects in human ILD
      and, hence, is suitable for their diagnosis and therapy.

PMID- 29367922
TI  - Baseline Susceptibility of Filarial Vector Culex quinquefasciatus (Diptera:
      Culicidae) to Five Insecticides with Different Modes of Action in Southeast of
      Iran.
AB  - Background: Culex quinquefasciatus (Diptera: Culicidae) is an important vector
      for many human diseases. The aim of this study was to evaluate the susceptibility
      level of larval and adult stages of Cu. quinquefasciatus to different groups of
      WHO recommended insecticides for vector control. Methods: Larval stages of the
      Culex mosquitoes were collected from their natural habitats in Rafsanjan County
      at Kerman Province, southeast of Iran in 2016. Insecticide susceptibility status
      of adult female Cx. quinquefasciatus against DDT (4%), deltamethrin (0.05%),
      malathion 5%, and bendiocarb (0.1%) were determined using WHO standard
      insecticide susceptibility test. Additional test was carried out to determine the
      susceptibility status of larvae of Cx. quinquefasciatus to temephos. Bioassay
      data were analyzed by Probit program. Results: Cx. quinquefasciatus adults showed
      resistance to all four groups of the tested insecticides according to the WHO
      criteria for resistance evaluation. The lethal concentrations for 50% mortality
      (LC50) and 90% mortality (LC90) of temephos against Cx. quinquefasciatus larvae
      were 0.18mg/l and 0.78mg/l, respectively. This finding also confirms resistance
      to temephos based on the WHO recommended instructions for resistance evaluation.
      Conclusion: Resistance to all groups of the tested insecticides should be
      considered for future vector control investigations in the study area.

PMID- 29367923
TI  - Brucellosis in Patients with Crimean-Congo Hemorrhagic Fever.
AB  - Background: Crimean-Congo hemorrhagic fever (CCHF) is a fatal zoonotic viral
      disease caused by infection with a tick-borne virus of the genus Nairovirus. In
      this study, we investigated the incidence of brucellosis in patients diagnosed
      with CCHF. Methods: Overall, 169 patients hospitalized with an initial diagnosis
      of CCHF were included in 2011 in Tokat/Turkey. Immunoglobulin M (IgM) antibodies
      and/or PCR results were used in the laboratory diagnosis of CCHF, while plate and
      standard tube agglutination (STA) tests were used to diagnose brucellosis.
      Results: Overall, 120 patients (79%) with positive PCR tests were diagnosed with
      CCHF. Five (4.16%) were also diagnosed with brucellosis based on the positive
      plate and STA test results. Four patients (2.36%) had negative CCHF PCR and
      positive STA test results. Conclusion: Brucellosis and CCHF can mimic each other
      and that all patients with CCHF or brucellosis should be screened for both
      conditions.

PMID- 29367924
TI  - Evaluation of Deltamethrin in Combination of Piperonyl Butoxide (PBO) against
      Pyrethroid Resistant, Malaria Vector, Anopheles stephensi in IRS Implementation:
      an Experimental Semi-Filed Trial in Iran.
AB  - Background: The aim of this study was to evaluate different concentrations of
      deltamethrin combined with formulated piperonyl butoxide (PBO) synergist on
      various surfaces against the wild strain of Anopheles stephensi, the main malaria
      vector in Southern Iran under semi-field condition. Methods: Four concentrations
      of deltamethrin WG 25% (Tagros) and PBO 800EC-UV (Endura) were prepared and
      sprayed on the pre-designed surfaces in accordance with WHO alliance line of the
      IRS Micronair(r). The WHO's recommended bioassay kit and method was used during
      this study. Results: Comparing the mortality rate of mosquitoes, the results
      showed a significant difference between months after treatment of IRS (Indoor
      Residual Spraying) (P< 0.05) but didn't show any significant differences between
      days during the first and second months (P> 0.05).Statistical test revealed a
      significance difference between mortality rate of mosquitoes in exposing to
      concentrations of 1 and 4 (P< 0.05) which demonstrated effect of synergizing PBO
      on mortality rate. Conclusion: This research as the first semi-field trial on
      deltamethrin added to different concentrations of formulated PBO for IRS,
      indicates that deltamethrin+10X PBO is more effective than other concentrations.
      Therefore, using synergists can be suggested as a new tool for prevention of
      pyrethriod resistance, although more studies are recommended.

PMID- 29367919
TI  - Recent Developments and Applications of the MMPBSA Method.
AB  - The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been
      widely applied as an efficient and reliable free energy simulation method to
      model molecular recognition, such as for protein-ligand binding interactions. In
      this review, we focus on recent developments and applications of the MMPBSA
      method. The methodology review covers solvation terms, the entropy term,
      extensions to membrane proteins and high-speed screening, and new automation
      toolkits. Recent applications in various important biomedical and chemical fields
      are also reviewed. We conclude with a few future directions aimed at making
      MMPBSA a more robust and efficient method.

PMID- 29367925
TI  - Situational Analysis of Visceral Leishmaniasis in the Most Important Endemic Area
      of the Disease in Iran.
AB  - Background: Visceral leishmaniasis is one of the most important vector borne
      diseases in the world, transmitted by sand flies. Despite efforts to prevent the
      spread of the disease, cases continue worldwide. In Iran, the disease usually
      occurs in children under 10 years. In the absence of timely diagnosis and
      treatment, the mortality rate is 95-100%. The main objective of this study was to
      determine the spatial and temporal distribution of visceral leishmaniasis as well
      as its correlation with climatic factors for determining high-risk areas in an
      endemic focus in northwestern Iran. Methods: In this cross-sectional study, data
      on VL cases were collected from local health centers in Ardabil Province, Iran
      during 2001-2015 to establish a geodatabase using ArcGIS10.3. Data analysis was
      conducted using SPSS23 and ArcMap Spatial Analyst. MaxEnt model was used to
      determine ecologically suitable nichesfor the disease. Results: Two hotspots were
      found in Meshkinshahr and Germi counties with 59% and 23% of total cases,
      respectively. There was an increase in the incidence rate of VL in Ardabil County
      from 2.9 in 2009 to 9.2/100,000 population in 2015. There was no spatial
      autocorrelation between county and total number of cases (P> 0.05). Higher NDVI,
      lower altitude and southern aspects had positive effects on the presence
      probability of VL. Conclusion: The number of cases of this disease have been
      rising since 2013 and doubled in 2015. According to the derived distribution
      maps, the disease is spreading to new locations such as Ardabil and Namin
      counties.

PMID- 29367926
TI  - The Effects of Isolated Fractions of Mesobuthus eupeus Scorpion Venom on Humoral
      Immune Response.
AB  - Background: Many elements such as immunosuppressive, chemotactic and anti
      inflammatory peptide that could effect on human and animals physiologic system
      were determined in venom. This study evaluated the use of Mesobuthus eupeus
      scorpion venom fractions as an immunomodulator. Methods: The venom fractions
      collected from Khuzestan Province in South West of Iran were purified by ion
      exchange chromatography. Elution of the bounded elements was done by using a
      linear gradient of sodium chloride (0.1, 0.25, 0.5, 0.75, 1, 1.25, 1.5 and 2
      molar). The fractions were analyzed by Bradford spectrophotometric and SDS-PAGE
      method. After treatments of chicken with venom fractions and sheep red blood cell
      (SRBC), direct haemagglutination test in microtiter plate was used for the
      determination of the chicken SRBC antibody titer. Results: The fraction released
      by NaCl 1.25M had the highest protein concentration. The highest and lowest
      antibody titer was determined at the fifth (NaCl 0.75 molar) and seventh fraction
      (NaCl 1.25 molar), respectively. Conclusion: Different protein profile of
      isolated fractions, were associated with various effect on immune response. Both
      enhancing and suppressing of the chicken humoral immune response to SRBC were
      observed after M. eupeus faction's venom treatment. It is due to biological
      functions of venom components. Purification of these elements would provide the
      new agents for immune responses manipulation.

PMID- 29367927
TI  - Rearing and Biology of Phlebotomus sergenti, the Main Vector of Anthroponotic
      Cutaneous Leishmaniasis in Iran.
AB  - Background: Establishment of sand flies laboratory colonies is essential to
      understand various biological aspects of Phlebotominae sand flies. The aims of
      the current study were to establish the colony of Phlebotomus sergenti Parrot
      (1917), the main vector of anthroponotic cutaneous leishmaniasis in old world,
      and to study biological parameters of this species. Methods: The sand flies were
      reared at 26-28  degrees C temperature, 14:10 (light: dark) photoperiod and 70
      80% relative humidity. Larval diet was a composted mixture of rabbit faces and
      rabbit pellets which is prepared through a special process. First to fifth
      generations of P. sergenti were used to define biological parameters. Results:
      Results showed that, P. sergenti blood feeding percentage were 42% on chicken,
      21% on BALB/c and 37% on golden hamster. Average time of blood digestion, egg
      incubation, 1st instar larva, pupa and adult emerging was recorded at 3.4, 8.7,
      15, 33.3 and 41.2 days after blood feeding, respectively. Mean number of laid
      eggs was 55.1 and retained eggs were 35 per a female. Fecundity and production
      rate were 61.6%, and 42.2% respectively. Average longevity recorded at 15.2 days
      for females and 14.8 days for males. Conclusion: Colony of P. sergenti has been
      established for the first time in Iran. Average interval time from egg to adult
      of this species was 32.5 days. Chicken and golden hamster were recommended as a
      blood source for colony initiation and routine blood feeding, respectively.

PMID- 29367928
TI  - Dynamics of Transgenic Enterobacter cloacae Expressing Green Fluorescent Protein
      Defensin (GFP-D) in Anopheles stephensi Under Laboratory Condition.
AB  - Background: Enterobacter cloacae bacterium is a known symbiont of the most
      Anopheles gut microflora and nominated as a good candidate for paratransgenic
      control of malaria. However, the population dynamics of this bacterium within An.
      stephensi and its introduction methods to the mosquitoes have not yet been
      explored. Methods: Enterobacter cloacae subsp. dissolvens expressing green
      fluorescent protein and defensin (GFP-D) was used to study transstadial
      transmission and the course of time, larval habitat, sugar, and blood meal on
      dynamics of the bacterium in the mosquito life stages in the laboratory
      condition. The bacterial quantities were measured by plating samples and counting
      GFP expressing colonies on the Tet-BHI agar medium. Results: The E. cloacae
      population remained stable in sugar bait at least for eleven days whereas it was
      lowered in the insectary larval habitat where the bacteria inadequately recycled.
      The bacterium was weakly transmitted transstadially from larval to adult stage.
      The bacterial populations increased smoothly and then dramatically in the guts of
      An. stephensi following sugar and blood meal respectively followed by a gradual
      reduction over the time. Conclusion: Enterobacter cloacae was highly stable in
      sugar bait and increased tremendously in the gut of female adult An. stephensi
      within 24h post blood meal. Sugar bait stations can be used for introduction of
      the transgenic bacteria in a paratransgenic approach. It is recommended to
      evaluate the attraction of sugar bait in combination with attractive kairomones
      as well as its stability and survival rate in the semi-field or field conditions.

PMID- 29367930
TI  - Curbing Malaria: A New Hope through Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR) Technology.

PMID- 29367929
TI  - Case Report of Human Urinary Myiasis Caused by Clogmia albipunctata (Diptera:
      Psychodidae) with Morphological Description of Larva and Pupa.
AB  - Background: Urinary myiasis is a form of myiasis caused mainly by larvae of
      Fannia scalaris, Musca, Sarcophaga, Lucilia, Wohlfahrtia, Calliphora, and rarely
      by Eristalis and Clogmia albipunctata. Methods: This report presents a case of
      female patient complaining of dysuria and frequency of micturition associated
      with intermittent passage of small, motile, dark-colored worm-like organisms in
      urine. She was a married housewife aged 24 years old referred from the Tropical
      Outpatient Clinic of Beni-Suef University Hospital, Egypt. The patient was
      subjected to a full questionnaire sheet and investigations such as CBC, stool and
      urine analysis and urinary ultrasonography. Collected larvae and pupae from urine
      samples were examined macroscopically and microscopically. Results: The examined
      larvae and pupae belonged to C. albipunctata. Ivermectin was prescribed to the
      patient with complaint withdrawal and complete disappearance of the larvae from
      urine. Conclusion: This study reports the first case of urinary myiasis caused by
      C. albipunctata in Beni-Suef Governorate, the second in Egypt and third case
      worldwide. The study throws some light on the medical importance and management
      of urinary myiasis.

PMID- 29367931
TI  - Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections
      Needed to Control Neovascular Age-related Macular Degeneration.
AB  - Tetracyclines, especially doxycycline, play a role in the regulation of
      inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment
      of corneal angiogenesis or choroidal neovascularization with tetracyclines has
      been shown to be effective in animal models. The aim of this study was to
      evaluate the efficacy of oral doxycycline in reducing the total number of
      intraocular injections needed for controlling neovascular age-related macular
      degeneration in human patients. In this interventional case series, 28 random
      consecutive patients with neovascular age-related macular degeneration from
      Farabi Eye Hospital, Tehran, Iran were treated for 4 months with 200 mg
      doxycycline once a day after the first intravitreal bevacizumab injection in
      addition to standard therapy in agreement with as-needed regimen. After 12 months
      of follow-up, total number of injections, foveal thickness and visual acuity were
      compared to those at baseline and of similar studies. Similar to standard
      treatment, co-treatment with doxycycline was able to control active disease
      (intraretinal or subretinal fluid or leakage, new-onset of macular hemorrhage,
      and reduction of visual acuity more than 5 letters based on Early Treatment
      Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current
      study and standard treatment, respectively 3.14 vs. 5.92, P < 0.001).
      Furthermore, while better control of the foveal thickness was achieved (P <
      0.001), vision improvement was similar to that achieved with standard therapy (P
      > 0.05). If confirmed in larger studies, the findings of this interventional case
      series could provide a strategy to control neovascular age-related macular
      degeneration with fewer intraocular bevacizumab injections by co-administering a
      well-known oral agent-doxycycline.

PMID- 29367933
TI  - Topical Timolol Inhibits Corneal Neovascularization in Rabbits.
AB  - Timolol is a non-selective beta-adrenergic antagonist that is similar to
      propranolol. The mechanism through which these drugs act on the regression of
      neovascularization is largely unknown. However, it is thought that the drugs may
      act through vascular endothelial growth factor signaling, vasoconstriction, and
      vascular endothelial cell apoptosis. The aim of this study was to determine the
      effect of timolol on corneal neovascularization in rabbits. Neovascularization
      was induced in the eyes of 20 rabbits. Next, the rabbits were divided into two
      groups: the timolol (experimental) group received eye drops containing timolol
      0.5% twice per day; and the saline (control) group received saline drops twice
      per day for two weeks. After 7 days, the mean area of corneal neovascularization
      (presented as a percentage relative to baseline) was significantly lower in the
      timolol group than in the saline group (4.63 +/- 4.61% versus 58.39 +/- 6.31%, P
      < 0.001). After 2 weeks, the mean area of corneal neovascularization was 0.85 +/-
      1.33% in the timolol group and 1.73 +/- 2.06% in the saline group (P = 0.315).
      After the first week of treatment, timolol significantly reduced the area of
      neovascularization compared to control. Timolol may increase the rate of recovery
      from corneal neovascularization.

PMID- 29367932
TI  - The Role of Mitochondrial DNA (mtDNA) in the Development of Diabetic Retinopathy
      (DR): A Systematic Review.
AB  - Diabetic Retinopathy (DR) is the most prevalent health problem, which is
      influenced by environmental and genetic factors with an increasing prevalence.
      The current systematic review is focused on mtDNA modification, including
      polymorphism and mutation/deletion, with a direct effect on DR.This systematic
      search was initially done through PubMed, Cochrane, EMBASE, SCOPUS, and Web of
      Science without a restriction on the years of publication. The terms searched
      included ''mtDNA'', ''mitochondrial DNA'', ''diabetes'', ''diabetic'',
      ''retina'', and ''diabetic retinopathy''. Animal, cohort, cross-sectional, and in
      vitro studies, as well as case series, case reports, review articles, and Letters
      to Editor were excluded from this research.From 1528 resulting searched articles,
      only 12papers were finally chosen as the case-control studies considering mtDNA
      gene and DR. Actually, of these 12 articles, 8 studies were concerned with mtDNA
      polymorphisms (UCP1, UCP2, ROMO-1, and Mn-SOD) and 4 articles were related to
      mtDNA mutation (A3243G mutation in tRNALeu(UUR) gene and mtDNA deletion
      (DeltamtDNA 4977)).Some conflicting results were found between the selected
      genetic modifications of mtDNA, such as Mn-SOD, UCP1, DeltamtDNA 4977, tRNALeu
      (UUR), and ROMO-1.Finally, A3243G mutation in the tRNALeu (UUR) gene and rs660339
      and V16A polymorphisms of UCP2 and Mn-SOD genes were respectively considered as
      the most important factors in the pathogenesis of DR.

PMID- 29367934
TI  - A Promising Modified Procedure for Upper Eyelid Retraction-Associated Graves'
      Ophthalmopathy: Transconjunctival Lateral Levator Aponeurectomy.
AB  - Upper eyelid retraction is a characteristic feature of thyroid eye disease,
      including Graves' orbitopathy. In this study, a new surgical technique for
      correction of lid retraction secondary to Graves' orbitopathy is described.
      Sixteen eyelids of patients older than 18 years old underwent surgical correction
      for moderate to severe lid retraction secondary to Graves' orbitopathy. In this
      procedure, levator aponeurectomy was performed via a transconjunctival approach.
      Upper marginal reflex distance (MRD1) was measured before the surgery and at 1
      week, 3 months, and 6 months after the surgery. MRD1 was reduced significantly
      from preoperatively (mean: 7.84 mm) to 1 week after the surgery (mean: 3.59 mm)
      (P < 0.001). Three and six months after surgery, mean MRD1 was 5.09 mm and 5.10
      mm, respectively, showing that lid retraction was improved significantly (P <
      0.001). Lateral levator aponeurectomy via the transconjunctival approach is a
      simple, scar-less, quick procedure that has optimal stable outcome.

PMID- 29367935
TI  - A Contralateral Eye Study Comparing Corneal Biomechanics in Subjects with
      Bilateral Keratoconus with Unilateral Vogt's Striae.
AB  - The aim of this study was to analyze and compare corneal biomechanics in patients
      with bilateral keratoconus (KCN) with unilateral Vogt's striae. In this
      prospective contralateral study, visual acuity, refraction, and corneal
      biomechanical parameters were evaluated in patients with bilateral KCN with
      unilateral Vogt's striae using the Ocular Response Analyzer (ORA) (Reichert Inc.,
      Buffalo, NY) and Corvis ST (Oculus Optikgerate GmbH, Wetzlar, Germany). All
      patients underwent a comprehensive ophthalmic examination, including uncorrected
      distance visual acuity (UDVA), corrected distance visual acuity (CDVA),
      refraction (calculated by vectorial analysis), slit-lamp biomicroscopy, and
      Scheimpflug-based tomography. The patients enrolled in this study had a reliable
      diagnosis of bilateral clinical KCN with unilateral Vogt's striae based on slit
      lamp signs as well as corneal topographic/tomographic maps. Fifty patients aged
      18 to 40 years were included in this study. There was a significant difference in
      all clinical (distance visual acuity and refraction) and corneal biomechanical
      parameters between KCN eyes with and without unilateral Vogt's striae (all P <
      0.05). However, there were no significant differences in peak distance (P =
      0.291), corneal compensated intraocular pressure (IOPCC) (P = 0.08), and J45 (P =
      0.131) between the two groups. Most corneal biomechanical parameters, except for
      peak distance, IOPCC, and J45, showed a significant difference between KCN eyes
      with and without unilateral Vogt's striae. Vogt's striae may cause corneal
      biomechanical deterioration. This information could be used in clinical practice.

PMID- 29367936
TI  - Correlation between Macular Thickness and Visual Field in Early Open Angle
      Glaucoma: A Cross-Sectional Study.
AB  - The aim of this study was to correlate macular thickness and visual field
      parameters in early glaucoma. A total of 104 eyes affected with early glaucoma
      were examined in a cross-sectional, prospective study. Visual field testing using
      both standard automated perimetry (SAP) and shortwave automated perimetry (SWAP)
      was performed. Global visual field parameters, including mean deviation (MD) and
      pattern standard deviation (PSD), were recorded and correlated with spectral
      domain optical coherence tomography (SD-OCT)-measured macular thickness and
      asymmetry. Average macular thickness correlated significantly with all measures
      of visual field including MD-SWAP (r = 0.42), MD-SAP (r = 0.41), PSD-SWAP (r = 
      0.23), and PSD-SAP (r = -0.21), with P-values <0.001 for all correlations. The
      mean MD scores (using both SWAP and SAP) were significantly higher in the eyes
      with thin than in those with intermediate average macular thickness. Intraeye
      (superior macula thickness - inferior macula thickness) asymmetries correlated
      significantly with both PSD-SWAP (r = 0.63, P < 0.001) and PSD-SAP (r = 0.26, P =
      0.01) scores. This study revealed a significant correlation between macular
      thickness and visual field parameters in early glaucoma. The results of this
      study should make macular thickness measurements even more meaningful to glaucoma
      specialists.

PMID- 29367937
TI  - Bioinformatic Analysis of Coronary Disease Associated SNPs and Genes to Identify
      Proteins Potentially Involved in the Pathogenesis of Atherosclerosis.
AB  - Factors that contribute to the onset of atherosclerosis may be elucidated by
      bioinformatic techniques applied to multiple sources of genomic and proteomic
      data. The results of genome wide association studies, such as the
      CardioGramPlusC4D study, expression data, such as that available from expression
      quantitative trait loci (eQTL) databases, along with protein interaction and
      pathway data available in Ingenuity Pathway Analysis (IPA), constitute a
      substantial set of data amenable to bioinformatics analysis. This study used
      bioinformatic analyses of recent genome wide association data to identify a seed
      set of genes likely associated with atherosclerosis. The set was expanded to
      include protein interaction candidates to create a network of proteins possibly
      influencing the onset and progression of atherosclerosis. Local average
      connectivity (LAC), eigenvector centrality, and betweenness metrics were
      calculated for the interaction network to identify top gene and protein
      candidates for a better understanding of the atherosclerotic disease process. The
      top ranking genes included some known to be involved with cardiovascular disease
      (APOA1, APOA5, APOB, APOC1, APOC2, APOE, CDKN1A, CXCL12, SCARB1, SMARCA4 and
      TERT), and others that are less obvious and require further investigation (TP53,
      MYC, PPARG, YWHAQ, RB1, AR, ESR1, EGFR, UBC and YWHAZ). Collectively these data
      help define a more focused set of genes that likely play a pivotal role in the
      pathogenesis of atherosclerosis and are therefore natural targets for novel
      therapeutic interventions.

PMID- 29367938
TI  - Collagenous Gastritis and Helicobacter pylori Infection: A Mere Coincidence?
AB  - A 21-year-old woman presented to our clinic after 7 years of abdominal pain,
      diarrhea, and iron-deficiency anemia. Initial upper endoscopy revealed severe
      inflammation and nodularity of the gastric body and active Helicobacter pylori
      infection. After eradication therapy, esophagogastroduodenoscopy showed gastric
      atrophy with nodularity resolution. Histopathology revealed scattered plasma
      cells, eosinophils, and collagen deposition suggestive of collagenous gastritis.
      H. pylori can induce proinflammatory cytokines, resulting in fibroblast
      upregulation. Collagenous gastritis may be caused by an inflammatory response
      associated with type I, II, and III collagen. Although further research is
      warranted, we hypothesize that chronic inflammation from H. pylori may lead to
      collagenous gastritis.

PMID- 29367939
TI  - Late Presentation for Care Among Patients With Chronic Hepatitis C: Prevalence
      and Risk Factors.
AB  - Patients with chronic hepatitis C may have advanced fibrosis at first evaluation.
      Using the European Association for the Study of the Liver (EASL) definition
      (FibroScan(r) >9.5 kPa) for "late presenter for care" (LP), we found that 32%
      (169 of 527) of patients were LP. Being a LP was associated with increasing age
      and a history of alcohol overuse.

PMID- 29367940
TI  - Ex vivo Trophoblast-specific Genetic Manipulation Using Lentiviral Delivery.
AB  - In this protocol report, we describe a lentiviral gene delivery technique for
      genetic modification of the rat trophoblast cell lineage. Lentiviral packaged
      gene constructs can be efficiently and specifically delivered to the trophoblast
      cell lineage of the blastocyst. The consequences of 'gain-of-function' and 'loss
      of-function' blastocyst manipulations can be evaluated with in vitro outgrowth
      assays or following transfer to pseudopregnant rats.

PMID- 29367941
TI  - Using xCELLigence RTCA Instrument to Measure Cell Adhesion.
AB  - Cell adhesion to neighbouring cells and to the underlying extracellular matrix
      (ECM) is a fundamental requirement for the existence of multicellular organisms.
      As such, the formation, stability and dissociation of cell adhesions are subject
      to tight control in space and time and perturbations within the sophisticated
      adhesion machinery are associated with a variety of human pathologies. Here, we
      outline a simple protocol to monitor alterations in cell adhesion to the ECM, for
      example, following genetic manipulations or overexpression of a protein of
      interest or in response to drug treatment, using the xCELLigence real-time cell
      analysis (RTCA) system.

PMID- 29367942
TI  - [Depression Among Caregivers of HIV - Positive Injection Drug Users in Hanoi,
      2016].
AB  - Most of people who inject drugs in Vietnam live in their family homes and these
      living have formed the burden on caring. This study aimed at exploring the
      characteristic of depression of caregivers of HIV - positive injection drug users
      and relative factors. Cross - sectional assessment data were gathered from 138
      caregivers recruited from Hanoi city. About 20% of the study sample had a
      depressed condition from mild to extremely severe. Caregiver burden and family
      function were significantly associated with depression of caregivers. This study
      addressed the needs of intervention to improve family function and to decrease
      caregiver burden aimed at raising mental health of caregivers of HIV - positive
      injection drug users.

PMID- 29367943
TI  - Using Cystine Knot Proteins as a Novel Approach to Retarget Oncolytic Measles
      Virus.
AB  - Modified measles virus (MV) has effective oncolytic activity preclinically and is
      currently being investigated in clinical trials for various types of cancer. We
      investigated the use of cystine knot proteins (CKPs) to direct MV activity. CKPs
      are short polypeptides that bind their targets with high affinity. We used a CKP
      that binds alphavbeta3, alphavbeta5, and alpha5beta1 integrins with single-digit
      nanomolar affinity to retarget MV to the integrins (MV-CKPint). MV-CKPint
      infected, replicated in, and killed human glioblastoma, medulloblastoma, diffuse
      intrinsic pontine glioma (DIPG), and melanoma cancer cells in vitro, all of which
      express the target integrins. MV-CKPint activity was competitively blocked by
      echistatin, an integrin binding peptide. When the CKP was cleaved from the viral
      H protein at an included protease site, virus activity was abrogated. When
      delivered intravenously (i.v.), the retargeted virus reached a subcutaneous
      glioblastoma tumor bed and produced cytopathic effects similar to that shown by
      intratumoral injection of the virus. Because these target integrins are
      overexpressed by tumor vascular endothelium, MV-CKPint may allow for effective
      therapy with i.v. injection. These results indicate for the first time that CKPs
      can be used to retarget MV for a receptor of choice. In addition, MV-CKPint
      provides proof of principle for the use of a CKP of interest to retarget any
      enveloped virus for both oncolytic and gene therapy purposes.

PMID- 29367944
TI  - Development of a Safe and Effective Vaccinia Virus Oncolytic Vector WR-Delta4
      with a Set of Gene Deletions on Several Viral Pathways.
AB  - Despite the effectiveness of classic treatments and available diagnostic tools,
      cancer continues to be a leading world health problem, with devastating cancer
      related death rates. Advances in oncolytic virotherapy have shown promise as
      potentially effective treatment options in the fight against cancer. The
      poxviruses have many features that make them an attractive platform for the
      development of oncolytic vectors, with some candidates currently in clinical
      trials. Here, we report the design and generation of a new oncolytic vector based
      on the vaccinia virus Western Reserve (WR) strain. We show that the WR-Delta4
      virus, with the combined deletion of four specific viral genes that act on
      metabolic, proliferation, and signaling pathways (A48R, B18R, C11R, and J2R), has
      effective anti-tumor capabilities in vivo. In WR-Delta4-infected mice, we
      observed strong viral attenuation, reduced virus dissemination, and efficient
      tumor cell growth control in the B16F10 syngeneic melanoma model, with enhanced
      neutrophil migration and activation of tumor antigen-specific immune responses.
      This approach provides an alternative strategy toward ongoing efforts to develop
      an optimal oncolytic poxvirus vector.

PMID- 29367945
TI  - CD19 CAR T Cells Expressing IL-12 Eradicate Lymphoma in Fully Lymphoreplete Mice
      through Induction of Host Immunity.
AB  - Chimeric antigen receptor (CAR) T cell therapy represents a significant
      advancement in cancer therapy. Larger studies have shown ~90% complete remission
      rates against chemoresistant and/or refractory CD19+ leukemia or lymphoma.
      Effective CAR T cell therapy is highly dependent on lymphodepleting
      preconditioning, which is achieved through chemotherapy or radiotherapy that
      carries with it significant toxicities. These can exclude patients of low
      performance status. In order to overcome the need for preconditioning, we
      constructed fully mouse first and second generation anti-murine CD19 CARs with or
      without interleukin-12 (IL-12) secretion. To test these CARs, we established a
      mouse model to reflect the human situation without preconditioning. Murine second
      generation CAR T cells expressing IL-12 were capable of eradicating established B
      cell lymphoma with a long-term survival rate of ~25%. We believe this to be the
      first study in a truly lymphoreplete model. We provide evidence that IL-12
      expressing CAR T cells not only directly kill target CD19+ cells, but also
      recruit host immune cells to an anti-cancer immune response. This finding is
      critical because lymphodepletion regimens required for the success of current CAR
      T cell technology eliminate host immune cells whose anti-cancer activity could
      otherwise be harnessed by strategies such as IL-12-secreting CAR T cells.

PMID- 29367946
TI  - Erratum: Variable frequency of LRRK2 variants in the Latin American research
      consortium on the genetics of Parkinson's disease (LARGE-PD), a case of ancestry.
AB  - [This corrects the article DOI: 10.1038/s41531-017-0020-6.].

PMID- 29367947
TI  - The influence of gravity and light on locomotion and orientation of Heterocypris
      incongruens and Notodromas monacha (Crustacea, Ostracoda).
AB  - For future manned long-d uration space missions, the supply of essentials, such
      as food, water, and oxygen with the least possible material resupply from Earth
      is vital. This need could be satisfied utilizing aquatic bioregenerative life
      support systems (BLSS), as they facilitate recycling and autochthonous
      production. However, few organisms can cope with the instable environmental
      conditions and organic pollution potentially prevailing in such BLSS. Ostracoda,
      however, occur in eu- and even hypertrophic waters, tolerate organic and chemical
      waste, varying temperatures, salinity, and pH ranges. Thus, according to their
      natural role, they can link oxygen liberating, autotrophic algae, and higher
      trophic levels (e.g., fish) probably also in such harsh BLSS. Yet, little is
      known about how microgravity (ug) affects Ostracoda. In this regard, we
      investigated locomotion and orientation, as they are involved in locating mating
      partners and suitable microhabitats, foraging, and escaping predators. Our study
      shows that Ostracoda exhibit altered activity patterns and locomotion behavior
      (looping) in ug. The alterations are differentially marked between the studied
      species (i.e., 2% looping in Notodromas monacha, ~50% in Heterocypris
      incongruens) and also the thresholds of gravity perception are distinct, although
      the reasons for these differences remain speculative. Furthermore, neither
      species acclimates to ug nor orientates by light in ug. However, Ostracoda are
      still promising candidates for BLSS due to the low looping rate of N. monacha and
      our findings that the so far analyzed vital functions and life-history parameters
      of H. incongruens remained similar as under normal gravity conditions despite of
      its high looping rate.

PMID- 29367948
TI  - Viruslike Particles Encapsidating Respiratory Syncytial Virus M and M2 Proteins
      Induce Robust T Cell Responses.
AB  - Subunit vaccines provide a safe, focused alternative to conventional vaccines.
      However, these vaccines often require significant adjuvants and are particularly
      hard to target toward cytotoxic T lymphocyte (CTL) immunity. Viruslike particles
      (VLPs) provide biomaterial scaffolds with pathogen-like polyvalent structures
      making them useful platforms for biomimetic antigen delivery to the immune
      system. Encapsidation of antigens within VLPs has been shown to enhance antigen
      availability for CD8 T cell responses. Here, we examine the potential to generate
      complex responses to multiple subunit antigens localized within the same VLP
      particle. Two proteins of respiratory syncytial virus (RSV) with well
      characterized CD8 T cell responses, the matrix (M) and matrix 2 (M2) proteins,
      were successfully coencapsidated within the P22 VLP. Upon intranasal
      administration in mice, the particles stimulated CD8 T cell memory responses
      against both antigens. In addition, vaccination elicited tissue-resident T cell
      populations. Upon subsequent RSV challenge, P22-M/M2-treated mice displayed
      significantly reduced lung viral titers. This demonstrates the utility of the P22
      VLP in directing immune responses to multiple encapsidated viral antigens,
      demonstrating the potential of this technology to facilitate immunity to multiple
      targets simultaneously.

PMID- 29367950
TI  - KRAS Cold Turkey: Using microRNAs to target KRAS-addicted cancer.
AB  - Human cancers are driven by genetic mutations which cause aberrant activation of
      pro-growth pathways. Although cancers are uniquely dependent on the pro-growth
      signaling from oncogenic pathways, efforts to directly target these have been
      largely unsuccessful. One of the most common and drug resistant oncogenic drivers
      in colon cancer is the GTPase KRAS. It has been shown that colon cancers with
      KRAS driver mutations are also 'addicted' to proteins outside of the KRAS pathway
      due to aberrant re-wiring of cell signaling. A number of genes with a synthetic
      lethal relationship to mutant KRAS have been previously identified by RNAi
      screens. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene
      expression, and their expression is frequently dysregulated in cancers. Recently,
      we have used an innovative functional miRNA screening approach to identify miRNAs
      that inhibit the survival of KRAS-mutant cells but not KRAS-wild-type cells. MiR
      126 was one of the miRNAs that displayed this selective effect. We found that miR
      126 induced synthetic lethality in KRAS-Mutant cells via the down-regulation of
      the polo-like kinase signaling network and a number of genes specifically
      necessary for the growth of KRAS-Mutant tumors. This study offers a new way
      forward for exploiting the regulatory power of miRNAs to specifically target
      aberrant cell signaling in cancer.

PMID- 29367949
TI  - Microscale Biomaterials with Bioinspired Complexity of Early Embryo Development
      and in the Ovary for Tissue Engineering and Regenerative Medicine.
AB  - Tissue engineering and regenerative medicine (TERM) are attracting more and more
      attention for treating various diseases in modern medicine. Various biomaterials
      including hydrogels and scaffolds have been developed to prepare cells
      (particularly stem cells) and tissues under 3D conditions for TERM applications.
      Although these biomaterials are usually homogeneous in early studies, effort has
      been made recently to generate biomaterials with the spatiotemporal complexities
      present in the native milieu of the specific cells and tissues under
      investigation. In this communication, the microfluidic and coaxial electrospray
      approaches that we used for generating microscale biomaterials with the spatial
      complexity of both pre-hatching embryos and ovary in the female reproductive
      system were introduced. This is followed by an overview of our recent work on
      applying the resultant bioinspired biomaterials for cultivation of normal and
      cancer stem cells, regeneration of cardiac tissue, and culture of ovarian
      follicles. The cardiac regeneration studies show the importance of using
      different biomaterials to engineer stem cells at different stages (i.e., in vitro
      culture versus in vivo implantation) for tissue regeneration. All the studies
      demonstrate the merit of accounting for bioinspired complexities in engineering
      cells and tissues for TERM applications.

PMID- 29367951
TI  - Non-enhanced CT Maximum Intensity Projections for the Detection of Large Vessel
      Occlusions.
AB  - Background: Identification of large vessel occlusions (LVO) is important with
      recent guidelines supporting endovascular therapy in selected acute ischemic
      stroke patients. Many stroke centers perform CT angiography (CTA) in patients
      with suspected LVO, however this requires additional time and contrast
      administration. Non-enhanced CT maximum intensity projection (NECT-MIPs) may
      offer a rapid alternative to CTA. Methods: We retrospectively reviewed acute
      stroke patients with LVO in the UCSD Stroke Registry, presenting between 6/2014
      7/2016. NECT-MIPs were evaluated for presence of LVO. Gold standard comparison
      was to CTA. Results were stratified by level of training (Faculty, Fellow and
      Acute Care Practitioners [ACPs]). Inter-rater agreement was assessed using
      Fleiss' Kappa Coefficient. Results: We reviewed 24 patients using NECT-MIPs for
      the detection of LVO. Faculty had a sensitivity and specificity of 95% & 92% for
      ICA/M1, 42% & 100% for M2, and 67% & 96% for basilar occlusions. Fellows and ACPs
      had a sensitivity and specificity of 61% & 94% for ICA/M1, 19% & 83% for M2, and
      75% & 95% for basilar occlusions. Inter-rater agreement among Faculty readers was
      k=0.75 for ICA/M1, k=0.79 for M2 and k=0.14 for basilar occlusions. Among Fellows
      and ACPs, k=0.57 for ICA/M1, k=0.40 for M2, and k=0.27 for basilar occlusions.
      Conclusions: NECT-MIPs have high sensitivity and specificity for the detection of
      LVO when compared to CTA. Inter-rater agreement is fair and higher amongst more
      experienced reviewers. These results suggest that NECT-MIPs may be helpful to
      streamline the identification of LVO and reduce door to needle and door to
      intervention times.

PMID- 29367952
TI  - Machine learning of neural representations of suicide and emotion concepts
      identifies suicidal youth.
AB  - The clinical assessment of suicidal risk would be significantly complemented by a
      biologically-based measure that assesses alterations in the neural
      representations of concepts related to death and life in people who engage in
      suicidal ideation. This study used machine-learning algorithms (Gaussian Naive
      Bayes) to identify such individuals (17 suicidal ideators vs 17 controls) with
      high (91%) accuracy, based on their altered fMRI neural signatures of death and
      life-related concepts. The most discriminating concepts were death, cruelty,
      trouble, carefree, good, and praise. A similar classification accurately (94%)
      discriminated 9 suicidal ideators who had made a suicide attempt from 8 who had
      not. Moreover, a major facet of the concept alterations was the evoked emotion,
      whose neural signature served as an alternative basis for accurate (85%) group
      classification. The study establishes a biological, neurocognitive basis for
      altered concept representations in participants with suicidal ideation, which
      enables highly accurate group membership classification.

PMID- 29367953
TI  - Pulsed Cavitational Ultrasound Softening: a new non-invasive therapeutic approach
      of calcified bioprosthetic valve stenosis.
AB  - Background: The majority of prosthetic heart valves currently implanted are
      tissue valves that can be expected to calcify with time and eventually fail.
      Surgical or percutaneous redux valve replacement is associated with higher rate
      of complications. We propose a novel non-invasive therapeutic approach based on
      the use of pulsed cavitational ultrasound (PCU) to improve the valvular function
      of degenerative calcified bioprosthesis. Objectives: Our study aims to
      demonstrate in vitro and in vivo on an ovine model that PCU can significantly
      improve the bioprosthesis opening by softening remotely the calcified stiff
      cusps. Methods: All the experiments were performed on calcified bioprosthetic
      valves explanted from human patients. PCU was performed in vitro on calcified
      bioprosthesis mounted on a hydraulic bench with pulsatile flow (n=8) and in vivo
      on an ovine model with implanted calcified bioprosthesis (n=7). We used 3D
      echocardiography, pressure and flow sensors, quantitative stiffness evaluation
      using shear wave elastography, micro-CT imaging and histology to evaluate in
      vitro and in vivo the effect of PCU. Results: The transvalvular gradient was
      found to decrease by a mean of 50% after PCU in both in vitro (from 21.1+/-3.9 to
      9.6+/-1.7 mmHg, p<0.001) and in vivo setup (from 16.2+/-3.2 to 8.2+/-1.3 mmHg,
      p<0.001), with a decrease of valve stiffness (in vitro: from 105.8+/-9 to 46.6+/
      4 kPa, p<0.001; in vivo: from 82.6+/-10 to 41.7+/-7 kPa, p<0.001) and an increase
      of valve area (from 1.10+/-0.1 to 1.58+/-0.1 cm2, p<0.001). Histology and micro
      CT imaging showed modifications of calcification structure without loss of
      calcification volume or alteration of the leaflet superficial structures.
      Conclusions: We have demonstrated in vitro and in vivo that PCU can decrease a
      calcified bioprosthesis stenosis by softening the leaflets remotely. This new non
      invasive approach has the potential to improve the outcome of patients with
      severe bioprosthesis stenosis.

PMID- 29367954
TI  - POLR2C Mutations Are Associated With Primary Ovarian Insufficiency in Women.
AB  - Context: Primary ovarian insufficiency (POI) results from a premature loss of
      oocytes, causing infertility and early menopause. The etiology of POI remains
      unknown in a majority of cases. Objective: To identify candidate genes in
      families affected by POI. Design: This was a family-based genetic study. Setting:
      The study was performed at two academic institutions. Patients and Other
      Participants: A family with four generations of women affected by POI (n = 5).
      Four of these women, three with an associated autoimmune diagnosis, were studied.
      The controls (n = 387) were recruited for health in old age. Intervention: Whole
      genome sequencing was performed. Main Outcome Measure: Candidate genes were
      identified by comparing gene mutations in three family members and 387 control
      subjects analyzed simultaneously using the pedigree Variant Annotation, Analysis
      and Search Tool. Data were also compared with that in publicly available
      databases. Results: We identified a heterozygous nonsense mutation in a subunit
      of RNA polymerase II (POLR2C) that synthesizes messenger RNA. A rare sequence
      variant in POLR2C was also identified in one of 96 women with sporadic POI.
      POLR2C expression was decreased in the proband compared with women with POI from
      another cause. Knockdown in an embryonic carcinoma cell line resulted in
      decreased protein production and impaired cell proliferation. Conclusions: These
      data support a role for RNA polymerase II mutations as candidates in the etiology
      of POI. The current data also support results from genome-wide association
      studies that hypothesize a role for RNA polymerase II subunits in age at
      menopause in the population.

PMID- 29367955
TI  - Pharmacological Inhibition of Brain Fatty Acid Binding Protein Reduces Ethanol
      Consumption in Mice.
AB  - The endocannabinoid (eCB) system is involved in a wide range of behavioral
      disorders including alcoholism. Inhibition of fatty acid amide hydrolase (FAAH),
      the principal enzyme that degrades the eCB anandamide (AEA), which enhances AEA
      levels in the brain, significantly increases ethanol consumption and preference.
      In the present study, we examined whether pharmacological inhibition of fatty
      acid binding proteins (FABPs) 5 and 7, which blocks the transport of AEA to FAAH,
      and increase AEA levels in vivo also alters ethanol consumption and preference.
      Using a limited access two-bottle choice paradigm, we evaluated ethanol
      consumption in both male and female C57Bl/6 mice. Results showed a significant
      decrease in ethanol consumption in both males and females treated with SBFI26, an
      inhibitor of FABPs. Specifically, male and female mice treated with SBFI26
      consumed 24% and 42% less compared to mice receiving no injections, respectively.
      Subsequently, corticosterone was examined to evaluate the effects FABP5/7
      inhibition upon the stress response. We observed a significant elevation in
      corticosterone levels following restraint stress in SBFI26 treated females, with
      a weak effect seen in males as compared to vehicle. Based on our results,
      targeting of FABPs appears to play an important role in ethanol consumption that
      is differentially regulated in males and females, which is mediated by the stress
      response.

PMID- 29367956
TI  - Frequency of employer changes and their financial return: gender differences
      amongst German university graduates.
AB  - Gender differences in the frequency of employer changes and their financial
      return were examined in a sample of Bavarian university graduates. The search and
      matching theories were used to develop hypotheses which were then tested against
      each other. The results show that in the first few years after graduation women
      change employer more frequently than men. In large part this can be explained by
      gender differences in labor market structures, in particular the fact that a
      woman's first job is less likely to be in a large company, in an executive
      position or on a permanent contract and women tend to be less satisfied with
      their first job. After controlling for variance in these factors the coefficient
      changes sign, indicating that under similar circumstances men change employer
      more often. Furthermore, both men and women benefit financially from changing
      employer. The absolute return is higher for men, but as men tend to have a higher
      starting salary there is no gender difference in the relative return and hence no
      effect on the gender gap. The results are also discussed in the light of the
      specifics of the structure of the German labor market.

PMID- 29367957
TI  - Patient-Centeredness: A Best Practice for HBCU Health Professional Education
      Programs.
AB  - This study examined the influence of physicians' and nurses' patient-centeredness
      on the satisfaction of African American female Medicaid patients. A multigroup
      structural equation modeling design was used to test the hypothesized model and
      its stability across national random test (Nt=98) and cross-validation (Ncv=296)
      samples. The model fit well. Physician and nurse patient-centeredness
      significantly and consistently influenced patient satisfaction, explaining 73% of
      its variance. One standardized deviation increase in physician patient
      centeredness increased patient satisfaction, likelihood to recommend, and ratings
      of care by .698, .665, and .644 deviations. The corresponding effects for nursing
      were .643, .613, and .594. These effects were consistent across national random
      samples. The study offers an evidenced-based model that sheds light on provider
      patient-centered-ness' influence on African American female Medicaid patient
      satisfaction.

PMID- 29367958
TI  - Classification of MRI under the Presence of Disease Heterogeneity using Multi
      Task Learning: Application to Bipolar Disorder.
AB  - Heterogeneity in psychiatric and neurological disorders has undermined our
      ability to understand the pathophysiology underlying their clinical
      manifestations. In an effort to better distinguish clinical subtypes, many
      disorders, such as Bipolar Disorder, have been further sub-categorized into
      subgroups, albeit with criteria that are not very clear, reproducible and
      objective. Imaging, along with pattern analysis and classification methods,
      offers promise for developing objective and quantitative ways for disease subtype
      categorization. Herein, we develop such a method using learning multiple tasks,
      assuming that each task corresponds to a disease subtype but that subtypes share
      some common imaging characteristics, along with having distinct features. In
      particular, we extend the original SVM method by incorporating the sparsity and
      the group sparsity techniques to allow simultaneous joint learning for all
      diagnostic tasks. Experiments on Multi-Task Bipolar Disorder classification
      demonstrate the advantages of our proposed methods compared to other state-of-art
      pattern analysis approaches.

PMID- 29367959
TI  - Contactless, probeless and non-titrimetric determination of acid-base reactions
      using broadband acoustic resonance dissolution spectroscopy (BARDS).
AB  - pH determination is a routine measurement in scientific laboratories worldwide.
      Most major advances in pH measurement were made in the 19th and early 20th
      century. pH measurements are critical for the determination of acid base
      reactions. This study demonstrates how an acid-base reaction can be monitored
      without the use of a pH probe, indicator and titres of reagent. The
      stoichiometric reaction between carbonate and HCl acid yields specific quantities
      of CO2, which causes reproducible changes to the compressibility of the solvent.
      This in turn slows down the speed of sound in solution which is induced by a
      magnetic follower gently tapping the inner wall of the vessel. As a consequence
      the frequencies of the acoustic resonances in the vessel are reduced. This
      approach is called Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS)
      which harnesses this phenomenon for many applications. The acid-carbonate
      experiments have also been validated using H2SO4 acid and using both potassium
      and sodium counterions for the carbonate. This method can be used to interrogate
      strong acid-base reactions in a rapid and non-invasive manner using carbonate as
      the base. The data demonstrate the first example of a reactant also acting as an
      indicator. The applicability of the method to weak acids has yet to be
      determined. A novel conclusion from the study is that a person with a well
      trained ear is capable of determining the concentration and pH of a strong acid
      just by listening. This brings pH measurement into the realm of human perception.

PMID- 29367960
TI  - Photochemical transformation of lipoic acid-based ligands: probing the effects of
      solvent, ligand structure, oxygen and pH.
AB  - We have combined optical absorption with the Ellman's test to identify the
      parameters that affect the transformation of the 5-membered dithiolanes to thiols
      in lipoic acid (LA) and its derivatives during UV-irradiation. We found that the
      nature and polarity of the solvent, the structure of the ligands, acidity of the
      medium and oxygen can drastically affect the amount of photogenerated thiols.
      These findings are highly relevant to the understanding of the photochemical
      transformation of this biologically relevant compound, and would benefit the
      increasing use of LA-based ligands for the surface functionalization of various
      nanomaterials.

PMID- 29367961
TI  - Layered tin monoselenide as advanced photothermal conversion materials for
      efficient solar energy-driven water evaporation.
AB  - Solar energy-driven water evaporation lays a solid foundation for important
      photothermal applications such as sterilization, seawater desalination, and
      electricity generation. Due to the strong light-matter coupling, broad absorption
      wavelength range, and prominent quantum confinement effect, layered tin
      monoselenide (SnSe) holds a great potential to effectively harness solar
      irradiation and convert it to heat energy. In this study, SnSe is successfully
      deposited on a centimeter-scale nickel foam using a facile one-step pulsed-laser
      deposition approach. Importantly, the maximum evaporation rate of SnSe-coated
      nickel foam (SnSe@NF) reaches 0.85 kg m-2 h-1, which is even 21% larger than that
      obtained with the commercial super blue coating (0.7 kg m-2 h-1) under the same
      condition. A systematic analysis reveals that its good photothermal conversion
      capability is attributed to the synergetic effect of multi-scattering-induced
      light trapping and the optimal trade-off between light absorption and phonon
      emission. Finally, the SnSe@NF device is further used for seawater evaporation,
      demonstrating a comparable evaporation rate (0.8 kg m-2 h-1) to that of fresh
      water and good stability over many cycles of usage. In summary, the current
      contribution depicts a facile one-step scenario for the economical and efficient
      solar-enabled SnSe@NF evaporation devices. More importantly, an in-depth analysis
      of the photothermal conversion mechanism underneath the layered materials depicts
      a fundamental paradigm for the design and application of photothermal devices
      based on them in the future.

PMID- 29367963
TI  - Regioselective direct arylation of indoles on the benzenoid moiety.
AB  - Recent advances in transition metal-catalyzed selective C-H functionalization of
      indoles have garnered tremendous attention. Great efforts have been devoted to C2
      and C3 arylation because of the inherent reactivity of the pyrrole ring. Until
      recently, elegant methods have been developed to enable selective direct
      arylation on the benzenoid moiety at C4, C5, C6, and C7. This review highlights
      the contributions made in benzenoid direct arylation of indoles and presents
      their potential in organic synthesis.

PMID- 29367962
TI  - Ribosomal incorporation of backbone modified amino acids via an editing-deficient
      aminoacyl-tRNA synthetase.
AB  - The ability to incorporate non-canonical amino acids (ncAA) using translation
      offers researchers the ability to extend the functionality of proteins and
      peptides for many applications including synthetic biology, biophysical and
      structural studies, and discovery of novel ligands. Here we describe the high
      promiscuity of an editing-deficient valine-tRNA synthetase (ValRS T222P). Using
      this enzyme, we demonstrate ribosomal translation of 11 ncAAs including those
      with novel side chains, alpha,alpha-disubstitutions, and cyclic beta-amino acids.

PMID- 29367964
TI  - A copper-catalyzed reaction of 3-diazoindolin-2-imines with 2
      (phenylamino)ethanols: convenient access to spiro[indoline-3,2'-oxazolidin]-2
      imines.
AB  - 3-Diazoindolin-2-imines reacted with chiral 2-(phenylamino)ethanols under copper
      catalysis to furnish chiral spiro[indoline-3,2'-oxazolidin]-2-imines in good
      yields with excellent diastereoselectivity. The reaction undergoes a copper
      catalyzed cascade process involving the formation of copper carbene, C-N
      coupling, and C-O coupling.

PMID- 29367965
TI  - Prediction of topological property in TlPBr2 monolayer with appreciable Rashba
      effect.
AB  - A quantum spin Hall (QSH) insulator with high stability, large bulk band gap and
      tunable topological properties is crucial for both fundamental research and
      practical application due to the presence of dissipationless edge conducting
      channels. Recently, chemical functionalization has been proposed as an effective
      route to realize the QSH effect. Based on first-principles calculations, we
      predict that a two-dimensional TlP monolayer would convert into a topological
      insulator with the effect of bromination, accompanied by a large bulk band gap of
      76.5 meV, which meets the requirement for room-temperature application. The
      topological nature is verified by the calculation of Z2 topological invariant and
      helical edge states. Meanwhile, an appreciable Rashba spin splitting of 77.2 meV
      can be observed. The bulk band gap can be effectively tuned with external strain
      and electric field, while the Rashba spin splitting shows a parabolic variation
      trend under an external electric field. We find that the topological property is
      available for the TlP film when the coverage rate is more than 0.75. BN and SiC
      are demonstrated as promising substrates to support the topological nature of
      TlPBr2 film. Our findings suggest that a TlPBr2 monolayer is an appropriate
      candidate for hosting the nontrivial topological state and controllable Rashba
      spin splitting, and shows great potential applications in spintronics.

PMID- 29367966
TI  - Electrocatalytic CO2 reduction by a cobalt bis(pyridylmonoimine) complex: effect
      of acid concentration on catalyst activity and stability.
AB  - A Co complex with a redox-active bis(pyridylmonoimine) ligand has been prepared
      and shows catalytic activity for electrochemical CO2 reduction in acetonitrile.
      Addition of a proton source such as water or trifluoroethanol dramatically
      improves the activity and stability of the molecular catalyst. The Co complex
      reduces CO2 to CO selectively at -1.95 V vs. Fc+/0 in the presence of high
      concentrations of water. The activity of the Co complex for CO2 reduction
      compares favorably to other molecular Co-based catalysts in acetonitrile
      solutions.

PMID- 29367967
TI  - PBTTT-C16 sol-gel transition by hierarchical colloidal bridging.
AB  - A versatile conjugated polymer, poly(2,5-bis(3-hexadecyllthiophen-2-yl)thieno[3,2
      b]thiophene) (pBTTT-C16, with Mw = 61 309 g mol-1), in a relatively good solvent
      (chlorobenzene, CB) medium is shown to produce gels through hierarchical
      colloidal bridging. Multiscale static/dynamic light and X-ray scattering analysis
      schemes along with complementary microscopy imaging techniques clearly reveal
      that upon cooling from the solution state at 80  degrees C to various gelation
      temperatures (5, 10, and 15  degrees C), rod-like colloidal pBTTT-C16 aggregates
      morph into spherical ones, triggering hierarchical colloid formation and bridging
      that eventually turn the solution into a gel after about one-day aging. A certain
      fraction of primal packing units-spherical gelators (~1 nm in mean radius)
      constitute the spherical building particles (~10 nm) noted above, which in turn
      constitute loose-packing aggregate clusters (~300 nm) in the sol state. As
      gelation proceeds, the aggregate cluster interiors tighten substantially, and
      micrometer-sized clusters (~3 MUm) formed by them begin to take shape and further
      interconnect to form the gel network (mean porosity size ~240 nm and spatial
      inhomogeneity length ~20 MUm). Rheological measurements and kinetic analysis
      reveal that the gelation temperature can also have a notable impact on gel
      microstructure, gelation rate, and mechanical strength, resulting in, for
      instance, a prominently nonergodic and porous structure for the soft gel
      incubated at a higher temperature T = 15  degrees C. The ac conductivity exhibits
      a notable upturn near pBTTT-C16/CB gelation, well above those achieved by the
      counterpart pBTTT-C14 solutions, which, in interesting contrast, cannot be
      brought to the gel phase under similar experimental conditions.

PMID- 29367968
TI  - Efficient and selective hydrogenation of C-O bonds with a simple sodium formate
      catalyzed by nickel.
AB  - A Ni-catalyzed hydrogenation of C-O compounds with sodium formate is developed.
      Various esters, i.e. aryl, alkenyl, benzyl pivalates, and even the aryl ethers,
      were efficiently reduced with a loading of nickel catalysts down to 0.5 mol%.
      Reactive functional groups such as C-C double bonds, carbonyl, CN, MeS and
      halogen groups are tolerable. This reaction can be used for the modification of
      complex molecules and carried out at a large scale.

PMID- 29367974
TI  - Natural Product Reports 35 years on.

PMID- 29367975
TI  - Se@SiO2-FA-CuS nanocomposites for targeted delivery of DOX and nano selenium in
      synergistic combination of chemo-photothermal therapy.
AB  - In this study, a versatile tumor-targeted and multi-stimuli-responsive drug
      delivery vehicle (Se particle@porous silica-folic acid-copper sulfide/doxorubicin
      (Se@SiO2-FA-CuS/DOX)) was fabricated for combined photothermal therapy with
      chemotherapy in cancer treatment. Due to excellent targeting ability, the Se@SiO2
      FA-CuS/DOX nanocomposites actively accumulated in tumor tissues and thus provided
      photothermal therapy under NIR irradiation and chemotherapy through the release
      of DOX and Se. Owing to the synergistic effect of chemotherapy (Se and DOX) and
      photothermal therapy, the Se@SiO2-FA-CuS/DOX nanocomposites could efficiently
      inhibit cancer cells both in vitro and in vivo and even completely eliminate
      tumors. Moreover, as the toxicity of DOX could be reduced by Se, the treatment
      using Se@SiO2-FA-CuS/DOX nanocomposites exhibited no appreciable adverse
      reactions. Thus, the Se@SiO2-FA-CuS/DOX nanocomposites have great potential as a
      multifunctional nanoplatform in future clinical applications.

PMID- 29367976
TI  - Hierarchically structured multi-shell nanotube arrays by self-assembly for
      efficient water oxidation.
AB  - Photosynthesis in plants occurs at structures which form by self-assembly under
      ambient conditions, while catalysts used for artificial photosynthesis normally
      need special conditions like high pressure or temperature. Herein, a facile and
      cost effective way for the synthesis of a highly complex and efficient oxygen
      evolution reaction (OER) catalyst, formed solely by self-assembly in solution, is
      presented. Without the need for any instrumentation except for a glass beaker,
      highly active nickel-iron-copper multi-shell nanotube arrays are produced by
      immersion of a copper plate in three different solutions. Cu(OH)2 nanowires are
      first self-grown on a copper substrate in a basic solution and subsequently
      converted to novel iron-copper hydroxide nanotubes by immersion in an Fe3+
      solution by a sacrificial template-accelerated hydrolysis mechanism. Finally, an
      additional layer of nickel nanosheets is added by treating in a nickel chemical
      bath. The resulting electrode shows a current density as high as 100 mA cm-2 at
      an overpotential of 320 mV with a Tafel slope of 32 mV dec-1, while also
      exhibiting long time stability. The use of inexpensive first-row transition
      metals, simple preparation methods with no energy consumption, the unique
      hierarchical structure of the nanosheet covered nanotubes, and the high catalytic
      performance are remarkable, and this study may therefore lead to more convenient
      and competitive routes for water splitting.

PMID- 29367977
TI  - Modular tripodal receptors for the hydrosulfide (HS-) anion.
AB  - Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter and is
      predominantly speciated as HS- at physiological pH. Despite this importance,
      reversible binding of HS- to synthetic receptors remains rare and confined to
      highly-engineered receptor systems. Here we demonstrate the generality of
      reversible HS- binding in a family of tren-based receptors.

PMID- 29367978
TI  - In situ synchrotron XRD analysis of the kinetics of spodumene phase transitions.
AB  - The phase transition by thermal activation of natural alpha-spodumene was
      followed by in situ synchrotron XRD in the temperature range 896 to 940  degrees
      C. We observed both beta- and gamma-spodumene as primary products in
      approximately equal proportions. The rate of the alpha-spodumene inversion is
      first order and highly sensitive to temperature (apparent activation energy ~800
      kJ mol-1). The gamma-spodumene product is itself metastable, forming beta
      spodumene, with the total product mass fraction ratio fgamma/fbeta decreasing as
      the conversion of alpha-spodumene continues. We found the relationship between
      the product yields and the degree of conversion of alpha-spodumene to be the same
      at all temperatures in the range studied. A model incorporating first order
      kinetics of the alpha- and gamma-phase inversions with invariant rate constant
      ratio describes the results accurately. Theoretical phonon analysis of the three
      phases indicates that the gamma phase contains crystallographic instabilities,
      whilst the alpha and beta phases do not.

PMID- 29367979
TI  - CoC2O4.2H2O derived Co3O4 nanorods array: a high-efficiency 1D electrocatalyst
      for alkaline oxygen evolution reaction.
AB  - Energy conversion and storage systems such as water splitting metal-air batteries
      require high-performance and durable oxygen evolution reaction (OER) catalysts.
      Herein, we report the in situ development of self-standing Co3O4 nanorods array
      on Co foil (Co3O4 NA/CF) as a 1D OER catalyst electrode. Such Co3O4 NA/CF only
      needs overpotential of 308 mV to drive a geometrical catalytic current density of
      15 mA cm-2 in 1.0 M KOH with good long-term electrochemical durability. In
      addition, this catalyst achieves a high turnover frequency of 0.646 mol O2 s-1 at
      overpotential of 410 mV.

PMID- 29367980
TI  - Proton distribution in Sc-doped BaZrO3: a solid state NMR and first principle
      calculations analysis.
AB  - Perovskite-based material Sc-doped BaZrO3 is a promising protonic conductor but
      with substantially lower conductivities than its Y-doped counterpart. 1H solid
      state NMR spectroscopy in combination with DFT modelling was used to analyze the
      protonic distribution in BaZr1-xScxO3-x/2-y(OH)2y and its effect on charge
      carrier mobility. 1H single pulse and 1H-45Sc TRAPDOR MAS NMR experiments
      highlighted the mobile character of the proton charge carriers at room
      temperature, giving rise to a single broad resonance, protons hopping between
      multiple sites on the NMR timescale. At low temperatures, the protonic motion was
      successfully slowed down allowing direct observation of the various proton
      environments present in the structure. For x <= 0.15, DFT modelling suggested a
      tendency for strong dopant-proton association leading to Sc-OH-Zr environments
      with 1H NMR shifts of 4.8 ppm. The Zr-OH-Zr environment, H-bonded to a Sc-O-Zr,
      lies 32 kJ mol-1 higher in energy than the Sc-OH-Zr environment, suggesting that
      the Sc-OH-Zr environment is trapped. However, even at these low concentrations,
      Sc-Sc clustering could not be ruled out as additional proton environments with
      stronger 1H-45Sc dipolar couplings were observed (at 4.2 and 2.8 ppm). For x =
      0.25, DFT modelling on the dry material predicted that Sc-?-Sc environments were
      extremely stable, again highlighting the likelihood of dopant clustering. A large
      number of possible configurations exists in the hydrated material, giving rise to
      a large distribution in 1H chemical shifts and multiple conduction pathways. The
      1H shift was found to be strongly related to the length of the O-H bond and, in
      turn, to the hydrogen bonding and OOH distances. The breadth of the NMR signal
      observed at low temperature for x = 0.30 indicated a large range of different OH
      environments, those with lower shifts being generally closer to more than one Sc
      dopant. Lower DFT energy structures were generally associated with weaker H
      bonding environments. Both the calculations and the DFT modelling indicated that
      the protons tend to strongly bond to the Sc clusters, which, in conjunction with
      the higher energies of configurations containing Zr-OH-Zr groups, could help
      explain the lower conductivities recorded for the Sc-substituted BaZrO3 in
      comparison to its yttrium counterpart.

PMID- 29367981
TI  - Catastrophic depolymerization of microtubules driven by subunit shape change.
AB  - Microtubules exhibit a dynamic instability between growth and catastrophic
      depolymerization. GTP-tubulin (alphabeta-dimer bound to GTP) self-assembles, but
      dephosphorylation of GTP- to GDP-tubulin within the tubule results in
      destabilization. While the mechanical basis for destabilization is not fully
      understood, one hypothesis is that dephosphorylation causes tubulin to change
      shape, frustrating bonds and generating stress. To test this idea, we perform
      molecular dynamics simulations of microtubules built from coarse-grained models
      of tubulin, incorporating a small compression of alpha-subunits associated with
      dephosphorylation in experiments. We find that this shape change induces
      depolymerization of otherwise stable systems via unpeeling "ram's horns"
      characteristic of microtubules. Depolymerization can be averted by caps with
      uncompressed alpha-subunits, i.e., GTP-rich end regions. Thus, the shape change
      is sufficient to yield microtubule behavior.

PMID- 29367983
TI  - Water-soluble transition metal complexes of ruthenium(ii), osmium(ii),
      rhodium(iii) and iridium(iii) with chelating N-heterocyclic carbene ligands in
      hydrogenation and transfer hydrogenation catalysis.
AB  - The synthesis of novel Ru(ii), Os(ii), Rh(iii) and Ir(iii) mono-N-heterocyclic
      carbene (NHC) complexes with a pyridine substituent is reported. The reaction of
      the imidazolium salts bearing N-alkyl and sulfonated N-alkyl substituents with
      Ag2O leads to the formation of the corresponding Ag(i) complexes. The metal
      complexes are available in good yields via transmetallation reactions from the
      corresponding silver complexes and [ArMCl2]2, where Ar = p-cymene or Cp* and M =
      Ru, Os, Rh or Ir. While N-alkyl substituted NHC complexes are almost insoluble in
      water (1.55 mg ml-1), sulfonated N-alkyl substituted NHC complexes display good
      solubility in water (up to 400 mg mL-1). All complexes were examined as catalysts
      in the transfer hydrogenation of acetophenone, which is quantitatively and highly
      selective reduced to 1-phenylethanol and 1-cyclohexylethanol. Additionally, the
      water-soluble complexes were examined in the complete hydrogenation of
      acetophenone with hydrogen in an autoclave, showing high conversions compared to
      literature-known systems.

PMID- 29367982
TI  - Association of fatty acids and lipids metabolism in placenta with early
      spontaneous pregnancy loss in Chinese women.
AB  - The aim of the present study was to evaluate the association of fatty acids and
      lipids metabolism in placenta with early spontaneous pregnancy loss (ESPL) in
      Chinese women. Seventy women with ESPL and 29 healthy pregnant women who asked
      for legal induced abortion were included in the case and control groups,
      respectively. The gestational age of the subject foetuses in both the case and
      control groups ranged from 4 to 10 weeks. The total fatty acids composition in
      the decidual and villous tissues was detected by gas-liquid chromatography using
      a standard method. Metabonomics analysis of the decidual and villous tissues was
      conducted by ultra-performance liquid chromatography quadrupole time of flight
      mass spectrometry (UPLC-QTOFMS). The total C18:3n-3 in the decidual and villous
      tissues, total n-3 polyunsaturated fatty acid (n-3 PUFA) in the decidual tissue,
      and total C18:2n-6 in the villous tissue were all significantly lower in the case
      group than in the control group. The ratio of C20:4n-6/C20:5n-3 in villous tissue
      was significantly higher, but prostaglandin I2 as well as hydroxyeicosapentaenoic
      acid, leukotriene B5 and thromboxane B3 in the villous tissue were significantly
      lower in the case group than in the control group. In addition, the low content
      of lysophosphatide in the decidual and villous tissues and the low content of
      diacylglycerol in the villous tissue were also associated with the occurance of
      ESPL. In conclusion, the lack of essential fatty acids, high ratio of C20:4n
      6/C20:5n-3, abnormal eicosanoids metabolism and low content of lysophosphatide
      and diacylglycerol in the placenta were all potential risk factors for ESPL in
      Chinese.

PMID- 29367984
TI  - Contiguous multiple pi-coordination of pi-conjugated polyenes: bonding nature and
      charge delocalization behaviour of polyene-(palladium chain) sandwich clusters.
AB  - The contiguous multiple pi-coordination (CMpiC) bonds are formed at the molecular
      interface between the extended pi-conjugated sp2-carbon framework and metal-metal
      moieties. However, the static properties including the bonding nature of the
      CMpiC bonds have not been well-understood. Here we report the charge
      delocalization behavior and bonding nature of the polyene-(palladium chain)
      sandwich clusters. We observed the chain-length dependent 13C NMR chemical shifts
      of the terminal phenyl groups in [Pdm{Ph(CH[double bond, length as m
      dash]CH)m+1Ph}2][B(ArF)4]2 (m = 3, 4, 5, 6), showing the efficient delocalization
      of positive charge over the polyene ligands. Furthermore, the detailed molecular
      orbital analysis of several model clusters provides insights into the bonding
      nature of the MU-eta2:(eta2:)neta2- and MU-eta3:(eta2:)neta3-poylene palladium
      chain sandwich clusters, where the former type is attributed to the corner
      sharing Pd array and the latter to the edge-sharing/corner-sharing hybrid Pd
      array. The analogy of the MU-eta3:(eta2:)neta3-type with the carbonyl-bridge
      coordination is discussed. The Pd string in each mode of sandwich chain clusters
      has a weak M-M bonding interaction.

PMID- 29367985
TI  - Molecular electrostatic potential on the proton-donating atom as a theoretical
      descriptor of excited state acidity.
AB  - Organic photoacids with enhanced acidities in the excited states have received
      much attention both experimentally and theoretically because of their
      applications in nanotechnology and chemistry. In this study, we investigate the
      excited-state acidities of 14 hydroxyl-substituted aromatic photoacids, with a
      focus on using theoretical molecular electrostatic potential (MEP) as an
      effective descriptor for photoacidity. For these model photoacids, we applied
      time-dependent density functional theory (TDDFT) at the omegaB97X-D/6-31G(d)
      level to calculate the molecular electrostatic potentials of S1 excited states
      and show that the molecular electrostatic potential on the proton-donating atom
      exhibits a linear relationship with the observed excited-state logarithmic acid
      dissociation constant (pKa*). As a result, the molecular electrostatic potential
      on the proton-donating atom can be used to estimate the pKa* values based on
      simple TDDFT calculations for a broad range of hydroxyl-substituted aromatic
      compounds. Furthermore, we explore the molecular electrostatic potential as a
      quantum descriptor for the photoacidities of cationic photoacids, and show a
      universal behavior of the pKa*-MEP dependence. We also investigate the solvent
      effects on the photoacidity using TDDFT calculations with implicit solvent
      models. Finally, we discuss the physical insights implicated by the molecular
      electrostatic potential as a successful measure for photoacidity on the mechanism
      of proton transfer in the molecular excited states. This pKa* descriptor provides
      an effective means to quantify the tendency of excited-state proton transfer with
      a relatively small computational cost, which is expected to be useful in the
      design of functional photoacids.

PMID- 29367986
TI  - Ubiquitous deprotonation of terephthalic acid in the self-assembled phases on
      Cu(100).
AB  - We performed an exhaustive study of terephthalic acid (TPA) self-assembly on a
      Cu(100) surface, where first-layer molecules display two sequential phase
      transitions in the 200-400 K temperature range, corresponding to different stages
      of molecular deprotonation. We followed the chemical and structural changes by
      means of high-resolution X-ray photoelectron spectroscopy (XPS) and variable
      temperature scanning tunneling microscopy (STM), which were interpreted on the
      basis of density functional theory (DFT) calculations and photoemission
      simulations. In order to reveal the spectroscopic contributions of the molecules
      in different states of deprotonation, we modified the substrate reactivity by
      deposition of a small amount of Sn, which hampers the deprotonation reaction. We
      found that the characteristic molecular ribbons of the TPA/Cu(100) alpha-phase at
      a low temperature contain a significant fraction of partially deprotonated
      molecules, in contrast to the expectation of a fully protonated phase, where the
      self-assembly was claimed to be simply driven by the intermolecular double
      hydrogen bonds [OHO]. On the basis of our simulations, we propose a model where
      the carboxylate groups of the partially deprotonated molecules form single
      hydrogen bonds with the carboxylic groups of the fully protonated molecules.
      Using real time XPS, we also monitored the kinetics of the deprotonation
      reaction. We show that the network of mixed single and double hydrogen bonds
      inhibits further deprotonation up to ~270 K, whereas the isolated molecules
      display a much lower deprotonation barrier.

PMID- 29367987
TI  - Mechanistic insights into the tropo-inversion of the biphenyl moiety in chiral
      bis-amido phosphites and in their palladium(ii) complexes.
AB  - Chiral bis-amido phosphites L1 and L2 containing a diaminobiphenyl unit and a
      chiral alkoxy group derived from either (-)-menthol or 3-acetoxy deoxycholic
      methyl ester have been synthesised. Both L1 and L2 react with PdCl2(NCPh)2
      affording di- or mononuclear derivatives with formula trans-[Pd(MU-Cl)Cl(L)]2
      (1a, L = L1; 1b, L = L2) or trans-PdCl2(L)2 (2a, L = L1; 2b, L = L2) depending on
      the Pd : L molar ratio. The crystal structure of (M,P)-1a confirms the trans
      arrangement of the ligand L1 and shows an unusual puckering of the Pd2(MU-Cl)2
      core (theta 46 degrees ). Both the ligands L1 and L2 and their complexes (1 and
      2) are fluxional in solution as a consequence of the tropo-inversion of the
      diaminobiphenyl unit. For L1, L2, 1a and 2a a combined study including variable
      temperature 31P{1H} NMR spectroscopy and line shape analysis, Eyring plots and
      DFT calculations have shed light on the mechanism of the tropo-inversion.

PMID- 29367988
TI  - Designed transition metal catalysts for intracellular organic synthesis.
AB  - The development of synthetic, metal-based catalysts to perform intracellular
      bioorthogonal reactions represents a relatively new and important area of
      research that combines transition metal catalysis and chemical biology. The
      ability to perform reactions in cellulo, especially those transformations without
      a natural counterpart, offers a versatile tool for medicinal chemists and
      chemical biologists. With proper modification of the metal catalysts, it is even
      possible to direct a reaction to certain intracellular sites. This review
      highlights advances in this new area, from early work on intracellular functional
      group conversions to recent advances in intracellular synthesis of drugs,
      including cytotoxic agents. Both the fundamental and applied aspects of this
      approach to intracellular synthesis are reviewed.

PMID- 29367989
TI  - Synthesis and application of a water-soluble phosphorescent iridium complex as
      turn-on sensing material for human serum albumin.
AB  - A novel water-soluble cyclometallated iridium complex [Ir(pq-COOH)2FDS]- (pq-COOH
      = 2-phenylquinoline-4-carboxylic acid, FDS = 3-(2-pyridyl)-5,6-bis(4-sulfophenyl)
      1,2,4-triazine dianions) (abbreviated as Ir) was synthesized and its
      phosphorescent property was comprehensively studied. It was found that the
      complex exhibited strong phosphorescence, which peaked at 634 nm in neutral
      conditions (maximized at pH 8.0). Its phosphorescence decreased with an increase
      in acidity of the aqueous solution. At pH 2.0, the quenched phosphorescence could
      be resumed upon the addition of human serum albumin (HSA) because of the
      hydrophobic and electrostatic interactions between HSA and Ir. Based on this
      phenomenon, a "turn on" type phosphorescence probe was developed for the
      detection of HSA. Under optimal conditions, a wide calibration range of 1-280 nM
      was obtained with a limit of detection of 0.8 nM for HSA. The phosphorescence
      probe was successfully used for the determination of HSA in blood serum and urine
      samples.

PMID- 29367990
TI  - Facile, non-destructive characterization of 2d photonic crystals using UV-vis
      spectroscopy.
AB  - We present a simple and non-destructive method for characterizing and quantifying
      the quality of two-dimensional (2D) close-packed arrays of submicron dielectric
      spheres. Utilizing radiative losses of photonic modes created by the 2D crystals
      into dielectric substrates we are able to monitor the quality of the particle
      monolayer during assembly and the size evolution of the individual particles
      during dry etching. Using an advanced interfacial assembly technique we prepare
      particle monolayers on glass and characterize the spectral behaviour of the
      radiative loss regarding different lattice constants, dielectric substrates and
      layer qualities. The effect of diameter reduction during dry etching is analysed
      and a simple model is proposed, which enables non-destructive, on spot
      characterization of the particle layer with sub-20 nm resolution using UV-vis
      spectroscopy.

PMID- 29367991
TI  - Pressure-actuated monolithic acrylic microfluidic valves and pumps.
AB  - In this article, we describe a microfluidic device with embedded valves and pumps
      made exclusively of layers of acrylic glass. Flat acrylic sheets are carved out
      with a micromilling machine and bonded together by solvent bonding. The working
      principle of the valves is based on a thin flexible membrane (~100 MUm) machined
      on one acrylic sheet and actuated with pneumatic pressure. A completely closed
      valve resists a pressure difference of ~17 kPa (~2.5 psi), and when open, it can
      sustain flow rates of up to 100 MUL s-1. Pumping is achieved by combining two
      valves and a pumping chamber in series, which is also based on the bending of a
      thin acrylic membrane. The maximum flow rate obtained with this pumping mechanism
      is 20 MUL min-1. Acrylic is a popular rigid thermoplastic because it is
      inexpensive, making it ideal for mass production of disposable devices, and also
      because it has demonstrated compatibility with different biochemical assays. The
      physical and optical properties it shares with other thermoplastics could lead to
      this material being implemented for similar valves and pumps. As a proof-of
      concept of our technology, we implemented a controlled cell-staining assay in two
      parallel incubation chambers integrating four valves and one pump into one
      device. Our monolithic acrylic valves can enable the mass production of
      disposable microfluidic devices that require fluid control with pressure-actuated
      valves and aid in the automation of biochemical assays.

PMID- 29367992
TI  - Predicted detonation properties at the Chapman-Jouguet state for proposed
      energetic materials (MTO and MTO3N) from combined ReaxFF and quantum mechanics
      reactive dynamics.
AB  - The development of new energetic materials (EMs) with improved detonation
      performance but low sensitivity and environmental impact is of considerable
      importance for applications in civilian and military fields. Often new designs
      are difficult to synthesize so predictions of performance in advance is most
      valuable. Examples include MTO (2,4,6-triamino-1,3,5-triazine-1,3,5-trioxide) and
      MTO3N (2,4,6-trinitro-1,3,5-triazine-1,3,5-trioxide) suggested by Klapotke as
      candidate EMs but not yet successfully synthesized. We propose and apply to these
      materials a new approach, RxMD(cQM), in which ReaxFF Reactive Molecular Dynamics
      (RxMD) is first used to predict the reaction products and thermochemical
      properties at the Chapman Jouguet (CJ) state for which the system is fully
      reacted and at chemical equilibrium. Quantum mechanics dynamics (QMD) is then
      applied to refine the pressure of the ReaxFF predicted CJ state to predict a more
      accurate final CJ point, leading to a very practical calculation that includes
      accurate long range vdW interactions needed for accurate pressure. For MTO, this
      RxMD(cQM) method predicts a detonation pressure of PCJ = 40.5 GPa and a
      detonation velocity of DCJ = 8.8 km s-1, while for MTO3N it predicts PCJ = 39.9
      GPa and DCJ = 8.4 km s-1, making them comparable to HMX (PCJ = 39.5 GPa, DCJ =
      9.1 km s-1) and worth synthesizing. This first-principles-based RxMD(cQM)
      methodology provides an excellent compromise between computational cost and
      accuracy including the formation of clusters that burn too slowly, providing a
      practical mean of assessing detonation performances for novel candidate EMs. This
      RxMD(cQM) method that links first principles atomistic molecular dynamics
      simulations with macroscopic properties to promote in silico design of new EMs
      should also be of general applicability to materials synthesis and processing.

PMID- 29367993
TI  - The structures, water stabilities and photoluminescence properties of two types
      of iodocuprate(i)-based hybrids.
AB  - Although great progress has been made in hybrid iodocuprates(i) as lighting
      phosphors, the effects of aromatic and aliphatic structure directing agents
      (SDAs) on their water stability, structure and photoluminescence (PL) properties
      are still not clear. Herein, aromatic N-heterocyclic 1,2-di(4-pyridyl)ethylene
      (dpe), aliphatic N-heterocyclic 1,8-diazabicyclo[5.4.0]undec-7-ene (dbu) and N
      aminoethylpiperazine (app) were selected to be SDAs to construct two types of
      hybrid iodocuprates(i) via a facile in situ approach. Aromatic dpe-derived
      cations are successfully directed to form (Me2dpe)(CuI3) (1), (Me2dpe)n(Cu4I6)n
      (2), (Et2dpe)2(Cu6I10) (3), and (H2dpe)n(Cu2I4)n (4). Three of them contain
      unprecedented inorganic iodocuprate clusters or chains. The aliphatic N
      heterocyclic dbu- and app-derivative cations are responsible for the formation of
      (Hdbu)n(Cu2I3)n (5) and (H3app)2(Cu2I6).2I.2H2O (6), which contain a (Cu2I3)-
      chain and a (Cu2I6)4- binuclear cluster, respectively. For the first time, the
      influence mechanisms of the water stabilities of iodocuprate-based PL materials
      were disclosed, by analyzing the possible interactions between SDAs and water
      molecules. 1-2 are PL silent due to their "self-quenching effect". 3, 4 and5
      exhibit bright red, orange and yellow solid-state PL emissions at room
      temperature respectively, originating from the charge transfer between inorganic
      iodocuprate species and organic N-heterocycles. The co-template approach leads to
      multiple charge transfers in 6, which features a tunable PL behavior from bluish
      green to white by varying the excitation light, and has a quantum yield up to 43%
      (the highest value among hybrid iodocuprates containing (Cu2I6)4- clusters). The
      comparative study not only helps us to rationally synthesize iodocuprate-based PL
      materials with enhanced performance, but also provides a new method to obtain
      wavelength-dependent PL materials.

PMID- 29367994
TI  - Rapid resolution of carbohydrate isomers via multi-site derivatization ion
      mobility-mass spectrometry.
AB  - Identifying small sugar isomers can be challenging by ion mobility-mass
      spectrometry (IM-MS) alone due to their small collision cross section
      differences. Herein, we report IM-MS results for multi-site, covalent
      carbohydrate derivatization with 3-carboxy-5-nitrophenylboronic acid (3C5NBA).
      Following reaction in aqueous solutions at room temperature, 3C5NBA reacts with
      each mono- or disaccharide molecule to yield products that each have a
      distinguishable mobility signature. The reaction was rapid and resulted in the
      detection of products within 5 min after 3C5NBA was mixed with the analyte. Eight
      disaccharides that varied in linkage, composition, and configuration (alpha or
      beta) as well as four monosaccharides, d-glucose, d-galactose, d-mannose and d
      fructose, were included in this study. The derivatives' drift times showed
      significant shifts, with up to 3-fold gains in resolution when compared to
      previous literature reports. Moreover, the specific MS/MS fragmentation
      information gathered from these sugar derivatives provided further validation of
      the isomers' structures.

PMID- 29367995
TI  - Synthesis of branched and linear 1,4-linked galactan oligosaccharides.
AB  - We report the synthesis of linear and branched (1->4)-d-galactans. Four
      tetrasaccharides and one pentasaccharide were accessed by adopting a procedure of
      regioselective ring opening of a 4,6-O-naphthylidene protecting group followed by
      glycosylation using phenyl thioglycoside donors. The binding of the linear
      pentasaccharide with galectin-3 is also investigated by the determination of a co
      crystal structure. The binding of the (1->4)-linked galactan to Gal-3 highlights
      the oligosaccharides of pectic galactan, which is abundant in the human diet, as
      putative Gal-3 ligands.

PMID- 29367996
TI  - Catalytic effect of a single water molecule on the OH + CH2NH reaction.
AB  - In recent work, there has been considerable speculation about the atmospheric
      reaction of methylenimine (CH2NH), because this compound is highly reactive,
      soluble in water, and sticky, thus posing severe experimental challenges. In this
      work, we have revisited the kinetics of the OH + CH2NH reaction assisted by a
      single water molecule. The potential energy surfaces (PESs) for the water
      assisted OH + CH2NH reaction were calculated using the CCSD(T)//BH&HLYP/aug-cc
      pVTZ levels of theory. The rate coefficients for the bimolecular reaction
      pathways CH2NHH2O + OH and CH2NH + H2OHO were computed using canonical
      variational transition state theory (CVT) with small curvature tunneling
      correction. The reaction without water has four elementary reaction pathways,
      depending on how the hydroxyl radical approaches CH2NH. In all cases, the
      reaction begins with the formation of a single pre-reactive complex before
      producing abstraction and addition products. When water is added, the products of
      the reaction do not change, and the reaction becomes quite complex, yielding four
      different pre-reactive complexes and eight reaction pathways. The calculated rate
      coefficient for the OH + CH2NH (water-free) reaction at 300 K is 1.7 * 10-11 cm3
      molecule-1 s-1 and for OH + CH2NH (water-assisted), it is 5.1 * 10-14 cm3
      molecule-1 s-1. This result is similar to the isoelectronic analogous reaction OH
      + CH2O (water-assisted). In general, the effective rate coefficients of the water
      assisted reaction are 2~3 orders of magnitude smaller than water-free. Our
      results show that the water-assisted OH + CH2NH reaction cannot accelerate the
      reaction because the dominated water-assisted process depends parametrically on
      water concentration. As a result, the overall reaction rate coefficients are
      smaller.

PMID- 29367997
TI  - New rare earth hafnium oxynitride perovskites with photocatalytic activity in
      water oxidation and reduction.
AB  - RHfO2N perovskites with R = La, Nd and Sm show a GdFeO3-type structure and are
      semiconductors with band gaps of 3.35, 3.40 and 2.85 eV and relative dielectric
      constants of 30, 16 and 28 respectively. These compounds have adequate reduction
      and oxidation potentials to conduct the overall water splitting reaction, and the
      analogous perovskite LaZrO2N with a band gap of 2.8 eV shows photocatalytic
      activity under visible light irradiation for O2 evolution.

PMID- 29367998
TI  - Identification of a rhodium(iii) complex as a Wee1 inhibitor against TP53-mutated
      triple-negative breast cancer cells.
AB  - The rhodium(iii) complex 1 was identified as a potent Wee1 inhibitor in vitro and
      in cellulo. It decreased Wee1 activity and unscheduled mitotic entry, and induced
      cell damage and death in TP53-mutated triple-negative breast cancer cells. 1
      represents a promising scaffold for further development of more potent metal
      based Wee1 antagonists.

PMID- 29367999
TI  - Nonaqueous synthesis of metal cyanamide semiconductor nanocrystals for
      photocatalytic water oxidation.
AB  - Herein, we report nonaqueous synthesis of metal cyanamide semiconductor
      nanocrystals, including Ag2NCN nanorods (NRs), ZnNCN NRs and PbNCN nanoparticles.
      The as-prepared Ag2NCN NRs with a band gap of 2.35 eV are applied as
      photocatalysts for water oxidation. Their oxygen evolution rate (280.7 MUmol h-1
      g-1) is much higher than that of Ag2NCN microcrystals (24.0 MUmol h-1 g-1).

PMID- 29368000
TI  - A negative feedback loop based on proton-driven in situ formation of plasmonic
      molybdenum oxide nanosheets.
AB  - We report a negative feedback loop based on proton-driven in situ formation of
      plasmonic MoO3-x nanosheets. When the concentration of Cu2+ is below a certain
      level, the reaction of Cu2+ and glutathione (GSH) produces Cu+ and few protons.
      However, when the concentration of Cu2+ is above a certain threshold, the
      reaction of GSH and Cu2+ will generate enough protons in the system to initiate
      the redox reaction of GSH and MoO3 nanosheets, which generates plasmonic MoO3-x
      nanosheets. This process in turn inhibits the reaction of GSH and Cu2+, which
      sequesters the excess Cu2+ from the system. The formation of MoO3-x nanosheets
      lowers the concentration of protons in solution and turns off the production of
      MoO3-x nanosheets. More importantly, the threshold concentration of Cu2+ can be
      easily regulated by changing the concentration of MoO3 nanosheets.

PMID- 29368003
TI  - The Role of Angiotensin II/AT1 Receptor Signaling in Regulating Retinal
      Microglial Activation.
AB  - Purpose: This study explored whether the proangiogenic factor Angiotensin II
      (AngII) had a direct effect on the activation state of microglia via the
      Angiotensin type 1 receptor (AT1-R). Methods: Microglial dynamic activity was
      investigated in live retinal flatmounts from adult Cx3Cr1+/GFP mice under
      control, AngII (5 MUM) or AngII (5 MUM) + candesartan (0.227 MUM) conditions. The
      effects of intravitreal administration of AngII (10 mM) were also investigated at
      24 hours, with retinae processed for immunocytochemistry, flow cytometry, or
      inflammatory quantitative PCR arrays. Results: We found FACS isolated retinal
      microglia expressed AT1-R. In retinal flatmounts, microglia showed characteristic
      movement of processes under control conditions. Perfusion of AngII induced an
      immediate change in process length (-42%, P < 0.05) and activation state of
      microglia that was ameliorated by AT1-R blockade, suggesting a direct effect of
      AngII on microglia via the AT1-R. Intravitreal injection of AngII induced
      microglial activation after 24 hours, which was characterized by increased soma
      size (23%, P < 0.001) and decreased process length (20%, P < 0.05). Further
      analysis indicated a significant decrease in the number of microglial contacts
      with retinal neurons (saline 15.6 +/- 2.31 versus AngII 7.8 +/- 1.06, P < 0.05).
      Retinal cytokine and chemokine expression was modulated, indicative of an
      inflammatory retinal phenotype. Conclusions: We show that retinal microglia
      express AT1-R and their activation state is significantly altered by the
      angiogenic factor, AngII. Specifically, AngII may directly activate AT1-Rs on
      microglia and contribute to retinal inflammation. This may have implications for
      diseases like diabetic retinopathy where increases in AngII and inflammation have
      been shown to play an important role.

PMID- 29368004
TI  - Balanced Eyes See Stereopsis More Quickly, but Not More Finely.
AB  - Purpose: To quantify ocular sensory dominance and investigate its relationship to
      stereopsis. Method: A total of 69 subjects participated in the study. Ocular
      dominance was measured by a continuous flashing technique, with the tested eye
      viewing a Gabor patch increasing in contrast, and the fellow eye viewing a
      Mondrian noise decreasing in contrast. In each trial, the log ratio of Mondrian
      to Gabor's contrasts was recorded as a subject first detected the Gabor. We
      collected 50 trials for each eye and an interocular difference was analyzed with
      a rank-sum test. The z-value was used as the ocular dominance index (ODI) to
      quantify the degree of ocular dominance. A subject with ODI >= 2 was categorized
      as having a clear ocular dominance, and a subject with ODI < 2 was considered as
      having balanced eyes (unclear dominance). The stereoacuity was measured with
      random dot patterns with durations varying from 50 to 1000 ms. The best
      achievable stereoacuity (Dmin) and the integration time needed to acquire that
      (Tmin) were calculated. Results: A total of 30 subjects had balanced eyes and 39
      had clear ocular dominance. Tmin was significantly longer in subjects with clear
      ocular dominance than in subjects with balanced eyes (180.18 vs. 121.17 ms, P <
      0.01). Tmin was positively correlated with ODI (P < 0.01). However, Dmin in
      subjects with clear dominance was not different from that in subjects with
      balanced eyes (40.60 vs. 35.73 arcsec, P = 0.18). Conclusions: Ocular dominance
      is not associated with how fine the stereoacuity is, but rather how quickly the
      best stereoacuity is acquired.

PMID- 29368001
TI  - Pharmacokinetics, Tissue Localization, Toxicity, and Treatment Efficacy in the
      First Small Animal (Rabbit) Model of Intra-Arterial Chemotherapy for
      Retinoblastoma.
AB  - Purpose: Current intra-arterial chemotherapy (IAC) drug regimens for
      retinoblastoma have ocular and vascular toxicities. No small-animal model of IAC
      exists to test drug efficacy and toxicity in vivo for IAC drug discovery. The
      purpose of this study was to develop a small-animal model of IAC and to analyze
      the ocular tissue penetration, distribution, pharmacokinetics, and treatment
      efficacy. Methods: Following selective ophthalmic artery (OA) catheterization,
      melphalan (0.4 to 1.2 mg/kg) was injected. For pharmacokinetic studies, rabbits
      were euthanized at 0.5, 1, 2, 4, or 6 hours following intra-OA infusion. Drug
      levels were determined in vitreous, retina, and blood by liquid chromatography
      tandem mass spectrometry. To assess toxicity, angiograms, photography,
      fluorescein angiography, and histopathology were performed. For in situ tissue
      drug distribution, matrix-assisted laser desorption/ionization imaging mass
      spectrometry (MALDI-IMS) was performed. The tumor model was created by combined
      subretinal/intravitreal injection of human WERI-Rb1 retinoblastoma cells; the
      tumor was treated in vivo with intra-arterial melphalan or saline; and induction
      of tumor death was measured by cleaved caspase-3 activity. Results: OA was
      selectively catheterized for 79 of 79 (100%) eyes in 47 of 47 (100%) rabbits, and
      melphalan was delivered successfully in 31 of 31 (100%) eyes, without evidence of
      vascular occlusion or retinal damage. For treated eyes, maximum concentration
      (Cmax) in the retina was 4.95 MUM and area under the curve (AUC0->infinity) was
      5.26 MUM.h. Treated eye vitreous Cmax was 2.24 MUM and AUC0->infinity was 4.19
      MUM.h. Vitreous Cmax for the treated eye was >100-fold higher than for the
      untreated eye (P = 0.01), and AUC0->infinity was ~50-fold higher (P = 0.01).
      Histology-directed MALDI-IMS revealed highest drug localization within the
      retina. Peripheral blood Cmax was 1.04 MUM and AUC0->infinity was 2.07 MUM.h.
      Combined subretinal/intravitreal injection of human retinoblastoma cells led to
      intra-retinal tumors and subretinal/vitreous seeds, which could be effectively
      killed in vivo with intra-arterial melphalan. Conclusions: This first small
      animal model of IAC has excellent vitreous and retinal tissue drug penetration,
      achieving levels sufficient to kill human retinoblastoma cells, facilitating
      future IAC drug discovery.

PMID- 29368002
TI  - In Vivo Elasticity Mapping of Posterior Ocular Layers Using Acoustic Radiation
      Force Optical Coherence Elastography.
AB  - Purpose: We used acoustic radiation force optical coherence elastography (ARF
      OCE) to map out the elasticity of retinal layers in healthy and diseased in vivo
      rabbit models for the first time. Methods: A healthy rabbit eye was proptosed and
      imaged using ARF-OCE, by measuring the tissue deformation after an acoustic force
      is applied. A diseased retinal inflammation model was used to observe the
      contrast before and after disease formation. Retinal histologic analysis was
      performed to identify layers of the retina corresponding with the optical images.
      Results: The general trend of the retinal layer elasticity is increasing
      stiffness from the ganglion side to the photoreceptor side, with the stiffest
      layer being the sclera. In a healthy rabbit model, the mechanical properties
      varied from 3 to 16 kPa for the five layers that were identified via optical
      imaging and histology (3.09 +/- 0.46, 3.82 +/- 0.88, 4.53 +/- 0.74, 6.59 +/-
      2.27, 16.11 +/- 5.13 kPa). In the diseased model, we have induced optical damage
      in a live rabbit and observed a change in the stiffness trend in its retina.
      Conclusions: High sensitivity elasticity maps can be obtained using the ARF-OCE
      system to differentiate different retinal layers. Subtle changes in the
      mechanical properties during the onset of diseases, such as retinal degeneration,
      can be measured and aid in early clinical diagnosis. This study validates our
      imaging system for the characterization of retinal elasticity for the detection
      of retinal diseases in vivo.

PMID- 29368005
TI  - The Role of ERK1/2 Activation in Sarpogrelate-Mediated Neuroprotection.
AB  - Purpose: To characterize the mediators of 5-HT2A serotonin receptor-driven
      retinal neuroprotection. Methods: Albino mice were treated intraperitoneally with
      saline or sarpogrelate, a 5-HT2A antagonist, immediately before light exposure
      (LE). Following LE, retinas were harvested for a high-throughput phosphorylation
      microarray to quantify activated phosphorylated proteins in G protein-coupled
      receptor (GPCR) signaling. To confirm microarray results and define temporal
      changes, Western blots of select GPCR signaling proteins were performed. Since
      both methodologies implicated MAPK/ERK activation, the functional significance of
      sarpogrelate-mediated ERK1/2 activation was examined by inhibition of ERK1/2
      phosphorylation via pretreatment with the MEK inhibitor (MEKi) PD0325901. The
      degree of neuroprotection was evaluated with spectral-domain optical coherence
      tomography (SD-OCT) and electroretinography (ERG). To determine the effects of
      sarpogrelate on gene expression, a qPCR array measuring the expression of 84
      genes involved in oxidative stress and cell death was performed 48 hours post LE.
      Results: Sarpogrelate led to an activation of the MAPK/ERK pathway. Temporal
      analysis further demonstrated a transient activation of ERK1/2, starting with an
      early inhibition 20 minutes into LE, a maximum activation at 3 hours post LE, and
      a return to baseline at 7 hours post LE. Inhibition of ERK1/2 with MEKi
      pretreatment led to attenuation of sarpogrelate-mediated neuroprotection. LE
      caused significant changes in the expression of genes involved in iron
      metabolism, oxidative stress, and apoptosis. These changes were prevented by
      sarpogrelate treatment. Conclusions: Sarpogrelate-mediated retinal protection
      involves a transient activation of the MAPK/ERK pathway, although this pathway
      alone does not account for the full effect of neuroprotection.

PMID- 29368007
TI  - Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That
      Targets Specific Cone Subtypes.
AB  - Purpose: Human Crb1 is implicated in some forms of retinal degeneration,
      suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity
      genes are expressed in vertebrate retina, although their functional roles are not
      well understood. To gain further insight into Crb and photoreceptor maintenance,
      we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2
      2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b
      short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which
      disrupts the planar organization of RGB cones (red, green, and blue) by
      interfering with Crb2a/2b-based cone-cone adhesion. Methods: We used standard
      morphometric techniques to assess age-related changes in retinal cell densities
      in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX
      transgene on retinal structure and photoreceptor densities. Linear cell densities
      were measured in all retinal layers in radial sections with JB4-Feulgen
      histology. Planar (surface) densities of cones were determined in retinal flat
      mounts. Cell counts from wild-type and pt108b transgenic fish were compared with
      both a "photoreceptor maintenance index" and statistical analysis of cell counts.
      Results: Age-related changes in retinal cell linear densities and cone
      photoreceptor planar densities in wild-type adult zebrafish provided a baseline
      for analysis. Expression of Crb2b-sfEX caused progressive and selective
      degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones,
      and increased numbers of rod photoreceptors. Conclusions: These differential
      responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX
      suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.

PMID- 29368009
TI  - Percutaneous nephrolithotomy versus retrograde intrarenal surgery for pediatric
      patients with upper urinary stones: a systematic review and meta-analysis.
AB  - The objective of this study is to compare the efficacy and safety of the
      percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in
      surgical treatment of pediatric patients with upper urinary stones based on the
      published literature. A comprehensive literature search of Pubmed, Embase,
      Cochrane Library and CNKI was conducted to identify studies comparing outcomes of
      PCNL and RIRS for treating pediatric patients with upper urinary stones before
      May 2017. A total of 11 studies, including one randomized controlled trial, four
      retrospective case-control studies and six case series studies, containing 822
      children with upper urinary stones were included in this systematic review. Five
      of 11 including studies, containing 474 children with upper urinary stones were
      included in a meta-analysis. Significantly shorter hospital stay and fluoroscopy
      time were needed by RIRS than PCNL (WMD: 1.44 days, 95% CI 0.85, 2.04; p <
      0.00001) and (WMD: 72.72 s, 95% CI 52.13, 93.31; p < 0.00001). The overall
      complications were higher for PCNL compared with RIRS (OR 1.70, 95% CI 1.02,
      2.84; p = 0.04). However, the minor (Clavien I or II) and major (Clavien III-V)
      complications rates in the PCNL group were higher compared with RIRS group but
      the differences were not statistically significant, respectively (p > 0.05). RIRS
      also benefits from significantly less need for blood transfusion (OR 9.09, 95% CI
      1.66, 49.78; p = 0.01). No significant differences were found in initial, final
      stone-free rate, and operative times (p > 0.05). Our analysis suggested that RIRS
      turns out to be a safe and feasible procedure alternative to PCNL for children
      with upper urinary stones in selected cases. Because of the inherent limitations
      of the included studies, further large sample, prospective, multi-centric and
      randomized control trials should be undertaken to confirm our findings.

PMID- 29368006
TI  - The Adenosine Receptor Antagonist, 7-Methylxanthine, Alters Emmetropizing
      Responses in Infant Macaques.
AB  - Purpose: Previous studies suggest that the adenosine receptor antagonist, 7
      methylxanthine (7-MX), retards myopia progression. Our aim was to determine
      whether 7-MX alters the compensating refractive changes produced by defocus in
      rhesus monkeys. Methods: Starting at age 3 weeks, monkeys were reared with -3
      diopter (D; n = 10; 7-MX -3D/pl) or +3D (n = 6; 7-MX +3D/pl) spectacles over
      their treated eyes and zero-powered lenses over their fellow eyes. In addition,
      they were given 100 mg/kg of 7-MX orally twice daily throughout the lens-rearing
      period (age 147 +/- 4 days). Comparison data were obtained from lens-reared
      controls (-3D/pl, n = 17; +3D/pl, n = 9) and normal monkeys (n = 37) maintained
      on a standard diet. Refractive status, corneal power, and axial dimensions were
      assessed biweekly. Results: The -3D/pl and +3D/pl lens-reared controls developed
      compensating myopic (-2.10 +/- 1.07 D) and hyperopic anisometropias (+1.86 +/-
      0.54 D), respectively. While the 7-MX +3D/pl monkeys developed hyperopic
      anisometropias (+1.79 +/- 1.11 D) that were similar to those observed in +3D/pl
      controls, the 7-MX -3D/pl animals did not consistently exhibit compensating
      myopia in their treated eyes and were on average isometropic (+0.35 +/- 1.96 D).
      The median refractive errors for both eyes of the 7-MX -3D/pl (+5.47 D and +4.38
      D) and 7-MX +3D/pl (+5.28 and +3.84 D) monkeys were significantly more hyperopic
      than that for normal monkeys (+2.47 D). These 7-MX-induced hyperopic ametropias
      were associated with shorter vitreous chambers and thicker choroids. Conclusions:
      In primates, 7-MX reduced the axial myopia produced by hyperopic defocus,
      augmented hyperopic shifts in response to myopic defocus, and induced hyperopia
      in control eyes. The results suggest that 7-MX has therapeutic potential in
      efforts to slow myopia progression.

PMID- 29368008
TI  - [Cancer patients in operative intensive care medicine].
AB  - Cancer is one of the leading causes of death worldwide. New targeted and
      individualized therapies and drugs provide a survival benefit for an increasing
      number of patients, but can also cause severe side effects. An increasing number
      of oncology patients are admitted to intensive care units (ICU) because of cancer
      related complications or treatment-associated side effects. Postoperative care,
      respiratory distress and sepsis are the leading causes for admission. Tumor mass
      syndromes and tumor lysis may require urgent treatment. Traditional anticancer
      chemotherapy is associated with infections and immunosuppression. Newer agents
      are generally well-tolerated and side effects are mild or moderate, but
      overwhelming inflammation and autoimmunity can also occur. Cellular treatment,
      such as with chimeric antigen receptor modified T-cells, monoclonal and
      bispecific antibodies targeting immune effectors and tumor cells are associated
      with cytokine release syndrome (CRS) with hypotension, skin reactions and fever.
      It is related to excessively high levels of inflammatory cytokines. Immune
      checkpoint inhibitors can lead to immune-related adverse events (IRAEs), such as
      colitis and endocrine disorders. Noninfectious respiratory complications, such as
      pneumonitis can also occur. Recent studies revealed that short-term and medium
      term survival of cancer patients is better than previously expected. In this
      review article we summarize diagnostic and treatment strategies for common life
      threatening complications and emergencies requiring ICU admission. Furthermore,
      strategies for rational admission policies are presented.

PMID- 29368010
TI  - Importance of whole-body imaging with complete coverage of hands and feet in
      alveolar rhabdomyosarcoma staging.
AB  - BACKGROUND: Alveolar rhabdomyosarcoma commonly arises in the extremities and is
      characterized by aggressive biology and high frequency of metastases. Whole-body
      imaging is increasingly employed in pediatric oncology but not recommended as
      standard in the staging of soft-tissue sarcomas. OBJECTIVE: After observing
      patients with a large symptomatic alveolar rhabdomyosarcoma lesion and a smaller
      silent lesion in the more distal part of an extremity we sought to estimate the
      frequency of this constellation. MATERIALS AND METHODS: We retrospectively
      evaluated the data of prospectively registered paediatric patients (age <21
      years) with alveolar rhabdomyosarcoma in the SoTiSaR (Soft Tissue Sarcoma
      Registry) of the Cooperative Weichteilsarkom Studiengruppe (CWS) 09/2011-04/2015
      with regard to whole-body imaging. RESULTS: Seventy-five patients were eligible.
      Images of 57 patients had been submitted for reference consultation, including 80
      whole-body examinations in 36 patients. Among them were 5 patients (14%, 95%
      confidence interval 3-25%) who had been diagnosed because of a symptomatic lesion
      while an additional silent lesion in the distal part of an extremity had remained
      unnoticed and had only been detected by later whole-body imaging. It is
      noteworthy that in 42 (53%) of all 80 whole-body examinations, the hands and feet
      had been only partially covered or completely excluded. CONCLUSION: In alveolar
      rhabdomyosarcoma silent lesions can be overlooked when the distal parts of the
      limbs are not thoroughly examined and not completely covered by imaging. Missing
      them influences treatment decisions and prognosis. Our results should be
      considered when evaluating the potential role of whole-body imaging in
      rhabdomyosarcoma.

PMID- 29368011
TI  - Technical aspects of abdominal ultrasound and color Doppler assessment of bowel
      viability in necrotizing enterocolitis.

PMID- 29368012
TI  - Correction to: Ionizing radiation from computed tomography versus anesthesia for
      magnetic resonance imaging in infants and children: patient safety
      considerations.
AB  - The published version of this article incorrectly lists Dr. Joseph P. Cravero in
      the Department of Radiology at Boston Children's Hospital. Dr. Cravero's correct
      affiliation is given below.

PMID- 29368014
TI  - ?

PMID- 29368013
TI  - [Intensive care medicine and economics].

PMID- 29368015
TI  - [Evidence-based psychotherapy of addictive disorders].
AB  - BACKGROUND: Addictive disorders form the group of the most common mental
      disorders. A wide range of psychotherapeutic treatment interventions exists;
      however, the proportion of patients receiving evidence-based interventions or
      psychotherapeutic treatment in outpatient care is very low. OBJECTIVE: The aim of
      the present review was a systematic reassessment of the empirical evidence for
      the efficacy of the different forms of psychotherapeutic treatment,
      identification of new effective interventions and derivation of recommendations
      for treatment practitioners. MATERIAL AND METHODS: A comprehensive literature
      search in a multistage method in the relevant national and international data
      banks was conducted. Subsequent analysis of topical guidelines, systematic
      reviews and original studies about addictions and therapy was performed. RESULTS:
      A total of 3 topical national guidelines, 2 reviews and 16 original studies could
      be identified. In particular, cognitive behavioral therapy, behavioral
      interventions and motivational interventions could be identified as evidence
      based interventions for the treatment of addictive disorders. Hypnotherapy can be
      recommended alternatively for patients dependent on tobacco. Also interesting for
      practitioners could be new treatment methods, such as neurocognitive training and
      mindfulness-based interventions. CONCLUSION: At present, although of high
      quality, results from existing studies are sometimes inconsistent or are
      numerically insufficient with respect to special treatment options. Future
      studies are warranted with respect to different substance use disorders and
      further patient groups.

PMID- 29368017
TI  - [Increasing lipid exudation and vascular alterations associated with a choroidal
      nevus].

PMID- 29368016
TI  - Differential proteomic analysis reveals sequential heat stress-responsive
      regulatory network in radish (Raphanus sativus L.) taproot.
AB  - MAIN CONCLUSION: Differential abundance protein species (DAPS) involved in
      reducing damage and enhancing thermotolerance in radish were firstly identified.
      Proteomic analysis and omics association analysis revealed a HS-responsive
      regulatory network in radish. Heat stress (HS) is a major destructive factor
      influencing radish production and supply in summer, for radish is a cool season
      vegetable crop being susceptible to high temperature. In this study, the proteome
      changes of radish taproots under 40  degrees C treatment at 0 h (Control), 12 h
      (Heat12) and 24 h (Heat24) were analyzed using iTRAQ (Isobaric Tag for Relative
      and Absolute Quantification) approach. In total, 2258 DAPS representing 1542
      differentially accumulated uniprotein species which respond to HS were
      identified. A total of 604, 910 and 744 DAPS was detected in comparison of
      Control vs. Heat12, Control vs. Heat24, and Heat12 vs. Heat24, respectively. Gene
      ontology and pathway analysis showed that annexin, ubiquitin-conjugating enzyme,
      ATP synthase, heat shock protein (HSP) and other stress-related proteins were
      predominately enriched in signal transduction, stress and defense pathways,
      photosynthesis and energy metabolic pathways, working cooperatively to reduce
      stress-induced damage in radish. Based on iTRAQ combined with the transcriptomics
      analysis, a schematic model of a sequential HS-responsive regulatory network was
      proposed. The initial sensing of HS occurred at the plasma membrane, and then key
      components of stress signal transduction triggered heat-responsive genes in the
      plant protective metabolism to re-establish homeostasis and enhance
      thermotolerance. These results provide new insights into characteristics of HS
      responsive DAPS and facilitate dissecting the molecular mechanisms underlying
      heat tolerance in radish and other root crops.

PMID- 29368018
TI  - [Orbital screwdriver injury in a toddler].
AB  - Presentation of a patient with an orbital intracranial penetrating screwdriver
      injury. The patient had been playing with the screwdriver at the time of the
      accident, he fell and the screwdriver penetrated his right orbit. Imaging
      revealed the position of the foreign body, which went from the medial orbital
      wall, extraconal and medial of the right internal carotid artery, through the
      sella turcica to the dorsum sellae. The patient had no intracranial hemorrhage.
      There was hardly any bleeding. The surgical removal of the screwdriver was
      carried out without complications.

PMID- 29368019
TI  - [Unclear uveal tumor with bleeding].

PMID- 29368020
TI  - Resonance Raman spectroscopy of Fe-S proteins and their redox properties.
AB  - Resonance Raman spectra of Fe-S proteins are sensitive to the cluster type,
      structure and symmetry. Furthermore, bands that originate from bridging and
      terminal Fe-S vibrations in the 2Fe-2S, 3Fe-4S and 4Fe-4S clusters can be
      sensitively distinguished in the spectra, as well as the type of non-cysteinyl
      coordinating ligands, if present. For these reasons, resonance Raman spectroscopy
      has been playing an exceptionally active role in the studies of Fe-S proteins of
      diverse structures and functions. We provide here a concise overview of the
      structural information that can be obtained from resonance Raman spectroscopy on
      Fe-S clusters, and in parallel, refer to their thermodynamic properties (e.g.,
      reduction potential), which together define the physiological roles of Fe-S
      proteins. We demonstrate how the knowledge gained over the past several decades
      on simple clusters nowadays enables studies of complex structures that include Fe
      S clusters coupled to other centers and transient processes that involve cluster
      inter-conversion, biogenesis, disassembly and catalysis.

PMID- 29368021
TI  - Access to Safe, Timely, and Affordable Surgical Care in Uganda: A Stratified
      Randomized Evaluation of Nationwide Public Sector Surgical Capacity and Core
      Surgical Indicators.
AB  - BACKGROUND: Access to safe surgery is critical to health, welfare, and economic
      development. In 2015, the Lancet Commission on Global Surgery recommended that
      all countries collect surgical indicators to lend insight into improving surgical
      care. No nationwide high-quality data exist for these metrics in Uganda. METHODS:
      A standardized quantitative hospital assessment and a semi-structured interview
      were administered to key stakeholders at 17 randomly selected public hospitals.
      Hospital walk-throughs and retrospective reviews of operative logbooks were
      completed. RESULTS: This study captured information for public hospitals serving
      64.0% of Uganda's population. On average, <25% of the population had 2 h access
      to a surgically capable facility. Hospitals averaged 257 beds/facilities and
      there were 0.2 operating rooms per 100,000 people. Annual surgical volume was
      144.5 cases per 100,000 people per year. Surgical, anesthetic, and obstetrician
      physician workforce density was 0.3 per 100,000 people. Most hospitals reported
      having electricity, oxygen, and blood available more than half the time and
      running water available at least three quarters of the time. In total, 93.8% of
      facilities never had access to a CT scan. Sterile gloves, nasogastric tubes, and
      Foley catheters were frequently unavailable. Uniform outcome reporting does not
      exist, and the WHO safe surgery checklist is not utilized. CONCLUSION: The
      Ugandan public hospital system does not meet LCoGS targets for surgical access,
      workforce, or surgical volume. Critical policy and programmatic developments are
      essential to build surgical capacity and facilitate provision of safe, timely,
      and affordable surgical care. Surgery must become a public health priority in
      Uganda and other low resource settings.

PMID- 29368022
TI  - Cost-effective downstream processing of recombinantly produced pexiganan peptide
      and its antimicrobial activity.
AB  - Antimicrobial peptides (AMPs) have significant potential as alternatives to
      classical antibiotics. However, AMPs are currently prepared using processes which
      are often laborious, expensive and of low-yield, thus hindering their research
      and application. Large-scale methods for production of AMPs using a cost
      effective approach is urgently required. In this study, we report a scalable,
      chromatography-free downstream processing method for producing an antimicrobial
      peptide, pexiganan, using recombinant Escherichia coli (E. coli). The four helix
      bundle structure of the unique carrier protein DAMP4 was used to facilitate a
      simple and cheap purification process based on a selective thermochemical
      precipitation. Highly pure fusion protein DAMP4var-pexiganan was obtained at high
      yield (around 24 mg per 800 mL cell culture with a final cultivation OD600 ~ 2).
      The purification yield of DAMP4var-pexiganan protein is increased twofold with a
      72.9% of the protein recovery in this study as compared to the previous
      purification processes (Dwyer in Chem Eng Sci 105:12-21, 2014). The antimicrobial
      peptide pexiganan was released and activated from the fusion protein by a simple
      acid-cleavage. Isoelectric precipitation was then applied to separate the
      pexiganan peptide from the DAMP4var protein carrier. The final yield of pure bio
      produced pexiganan was 1.6 mg from 800 mL of bacterial cell culture (final
      cultivation OD600 ~ 2). The minimum bactericidal concentration (MBC) test
      demonstrated that the bio-produced pexiganan has the same antimicrobial activity
      as chemically synthesized counterpart. This novel downstream process provides a
      new strategy for simple and probable economic production of antimicrobial
      peptides.

PMID- 29368024
TI  - Metagenomic Analysis of the Jinding Duck Fecal Virome.
AB  - Ducks play an important role in transmitting and maintaining mammalian viruses in
      nature, and are a reservoir host of many animal viruses. We analyzed the fecal
      virome of four strains (A, B, C, and D) of ducks living in isolation by using
      metagenomic analysis. The feces of the ducks tested contained 18 animal virus
      families. The percentage values of RNA virus reads, compared to the total animal
      virus reads in each of the four strains were 96.96% (A), 97.30% (B), 98.01 (C),
      and 67.49% (D), and were mainly from Orthomyxoviridae, Mimiviridae, Bunyaviridae,
      Picobirnaviridae, and Reoviridae. Meanwhile, the minority of DNA virus reads were
      related to Herpesviridae, Adenoviridae, Iridoviridae, and other, low abundance
      viral families. The percentage values of Orthomyxoviridae, Mimiviridae,
      Bunyaviridae, Picobirnaviridae, and Herpesviridae reads were not significantly
      different among strains A, B, and C; however, there were marked differences in
      the abundance of these reads in strain D. In summary, this study provides an
      unbiased examination of the viral diversity in the feces of four strains of ducks
      in specific-pathogen-free periods, and highlights the variation in the percentage
      of viral families present. These results can be used as a reference for detecting
      duck viral pathogens and predicting zoonotic potential.

PMID- 29368027
TI  - [Implementation of interdisciplinary multimodal pain therapy according to OPS 8
      918 : Recommendations of the ad hoc commission for interdisciplinary multimodal
      pain therapy of the German Pain Association].
AB  - With the implementation of the German diagnosis-related groups (DRG)
      reimbursement system in hospitals, interdisciplinary multimodal pain therapy was
      incorporated into the associated catalogue of procedures (OPS 8-918). Yet, the
      presented criteria describing the procedure of interdisciplinary multimodal pain
      therapy are neither precise nor unambiguous. This has led to discrepancies in the
      interpretation regarding the handling of the procedure-making it difficult for
      medical services of health insurance companies to evaluate the accordance between
      the delivered therapy and the required criteria. Since the number of pain units
      has increased in recent years, the number of examinations by the medical service
      of health insurance companies has increased. This article, published by the ad
      hoc commission for interdisciplinary multimodal pain therapy of the German Pain
      Association, provides specific recommendations for correct implementation of
      interdisciplinary multimodal pain therapy in routine care. The aim is to achieve
      a maximum level of accordance between health care providers and the requirements
      of the medical examiners from health insurance companies. More extensive criteria
      regarding interdisciplinary multimodal pain treatment in an in-patient setting,
      especially for patients with chronic and complex pain, are obviously needed.
      Thus, the authors further discuss specific aspects towards further development of
      the OPS-code. However, the application of the OPS-code still leaves room
      regarding treatment intensity and process quality. Therefore, the delivery of
      pain management in sufficient quantity and quality still remains the
      responsibility of each health care provider.

PMID- 29368023
TI  - Variability in the prescription of biological drugs in rheumatoid arthritis in
      Spain: a multilevel analysis.
AB  - To describe variability in the prescription of biologics (B-DMARDs) for patients
      with rheumatoid arthritis (RA) in hospitals in Spain, and to explore which
      characteristics of the patient, the doctor and the hospital are associated with
      this variability. Cross-sectional multicentric study in 46 rheumatology services
      of the National Health System. Medical records of 1188 randomly selected patients
      were reviewed. The association of each variable with B-DMARD prescription was
      analyzed using simple logistic regressions. Multilevel logistic regression models
      were created to analyze variability among centers. 36.8% of patients had received
      B-DMARD. The proportion of patients being treated with B-DMARDs varied between
      3.6 and 71.4% depending on the center. Association of prescription of B-DMARD
      with patient age (OR = 0.958, 95% CI = 0.947-0.968, p < 0.001), longer disease
      duration (OR = 1.05, 95% CI = 1.032-1.069, p < 0.001), higher CRP levels (OR =
      1.022, 95% CI = 1.003-1.042, p = 0.023), and higher number of hospitalizations
      (OR = 1.286, 95% CI = 1.145-1.446, p < 0.001) was observed. With regard to the
      center characteristics, the existence of telephone consultations (OR = 1.438, 95%
      CI = 1.037-1.994, p = 0.03) and the number of beds (OR = 1.045, 95% CI = 1.001
      1.091, p = 0.044) were positively associated with prescription of B-DMARDs.
      Patient variables explained 34.04% of the variability among centers. By adjusting
      for patient and hospital characteristics, it went up to 83.71%. There is
      variability in the prescription of B-DMARDs for patients with RA among hospitals
      which is associated, to a greater extent, with the center characteristics. B
      DMARDs prescription could be partly explained by other factors not covered by the
      current study including the provider's attitudes towards biologics and other
      hospital characteristics.

PMID- 29368026
TI  - Fungal Diversity of Human Gut Microbiota Among Eutrophic, Overweight, and Obese
      Individuals Based on Aerobic Culture-Dependent Approach.
AB  - Fungi have a complex role in the intestinal tract, influencing health and
      disease, with dysbiosis contributing to obesity. Our objectives were to
      investigate fungal diversity in human gut microbiota among eutrophic, overweight,
      and obese. Epidemiological and nutritional information were collected from adult
      individuals, as well as stool samples processed for selective fungi isolation and
      identification by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry (yeasts) or microculture (filamentous fungi). Further 18S rDNA
      sequencing was performed to confirm identification. The mean count of fungi was
      241 CFU/g of feces. Differences in the population level of the filamentous fungi
      were observed within eutrophic and obese groups. Overall, 34 genera were
      identified. The predominant phylum was Ascomycota with 20 different genera,
      followed by Basidiomycota and Zygomycota. As for Ascomycota, the most prevalent
      species were Paecilomyces sp., Penicillium sp., Candida sp., Aspergillus sp.,
      Fonsecaea sp., and Geotrichum sp. (76.39, 65.28, 59.72, 58.33, 12.50, and 9.72%,
      respectively). As for Basidiomycota, Trichosporon sp. and Rhodotorula sp. were
      the most prevalent (30.56 and 15.28%, respectively), and for Zygomycota, Rhizopus
      sp. and Mucor sp. were the most numerous (15.28 and 9.72%, respectively). As
      expected there is a mycobiota shift towards obesity, with slightly higher
      diversity associated to eutrophic individuals. This mycobiota shift seems also to
      be related to the nutritional behavior of the individuals, as observed that the
      macronutrients intake may be positively related to the different fungi
      occurrences. Other studies are needed to better understand relationships between
      mycobiota and obesity, which could be used in future obesity treatments.

PMID- 29368025
TI  - The Changes of Colonic Bacterial Composition and Bacterial Metabolism Induced by
      an Early Food Introduction in a Neonatal Porcine Model.
AB  - The impact of an early food introduction on the microbiota composition and
      microbial metabolism in colon was investigated using a new-born piglet model. At
      day 4 after birth, 10 litters of piglets were randomly allocated to a sow-rearing
      group (SR group) and a milk-replacer supplementing group (MRS group) (n = 5). A
      commercial milk replacer was given to the suckling piglets in the MRS group from
      the 4th day to the 28th day. Pyrosequencing of the V3-V4 region of the 16S rRNA
      genes showed that the milk replacer supplementation significantly decreased the
      relative abundance of Lactobacillus, Clostridium XI, Blautia, Clostridium
      sensustricto and Escherichia (p = 0.08) in the colon of the piglets, but
      significantly increased the relative abundance of Paraprevotella on the 28th day.
      In addition, the abundance of Rumminococcus, Clostridium XlVa, Succiniclasticum,
      Clostridium IV tended to increase in the MRS group. The concentrations of
      acetate, propionate, butyrate, valerate and branch-chain fatty acids (BCFAs) in
      the colonic digesta increased with the milk replacer supplementary in the MRS
      group. In addition, the milk replacer supplementary increased the expression
      level of Toll-like receptor 4 (TLR4), but decreased the expression level of
      interleukin-6 (IL-6) in the colonic mucosa of the piglets. In conclusion, an
      early food introduction can influence the gut bacterial composition and
      metabolism, and may further affect the intestinal health by modifying the gene
      transcription related to the colonic function. These findings may provide some
      guidelines for the early nutrition supplementation for infants during the
      lactation period.

PMID- 29368029
TI  - An investigation into the nutritional status of patients receiving an Enhanced
      Recovery After Surgery (ERAS) protocol versus standard care following
      Oesophagectomy.
AB  - PURPOSE: Enhanced Recovery After Surgery (ERAS) protocols have been effectively
      expanded to various surgical specialities including oesophagectomy. Despite
      nutrition being a key component, actual nutrition outcomes and specific
      guidelines are lacking. This cohort comparison study aims to compare nutritional
      status and adherence during implementation of a standardised post-operative
      nutritional support protocol, as part of ERAS, compared to those who received
      usual care. METHODS: Two groups of patients undergoing resection of oesophageal
      cancer were studied. Group 1 (n = 17) underwent oesophagectomy between Oct 2014
      and Nov 2016 during implementation of an ERAS protocol. Patients in group 2 (n =
      16) underwent oesophagectomy between Jan 2011 and Dec 2012 prior to the
      implementation of ERAS. Demographic, nutritional status, dietary intake and
      adherence data were collected. Ordinal data was analysed using independent t
      tests, and categorical data using chi-square tests. RESULTS: There was no
      significant difference in nutrition status, dietary intake or length of stay
      following implementation of an ERAS protocol. Malnutrition remained prevalent in
      both groups at day 42 post surgery (n = 10, 83% usual care; and n = 9, 60% ERAS).
      A significant difference was demonstrated in adherence with earlier initiation of
      oral free fluids (p <0.008), transition to soft diet (p <0.004) and continuation
      of jejunostomy feeds on discharge (p <0.000) for the ERAS group. CONCLUSION: A
      standardised post-operative nutrition protocol, within an ERAS framework, results
      in earlier transition to oral intake; however, malnutrition remains prevalent
      post surgery. Further large-scale studies are warranted to examine individualised
      decision-making regarding nutrition support within an ERAS protocol.

PMID- 29368028
TI  - Work Disability Trajectories Among Individuals with a Sick-Leave Spell Due to
      Depressive Episode >= 21 Days: A Prospective Cohort Study with 13-Month Follow
      Up.
AB  - Background Despite the increasing pattern of sick leave associated with
      depression in western countries, little is known about future work disability
      patterns among such sickness absentees. Aim To identify work disability (sick
      leave and disability pension) trajectories after the 21st day of a sick-leave
      spell due to depressive episode, and to investigate sociodemographic and
      morbidity characteristics of individuals in different trajectory groups. Methods
      This is a prospective cohort study using Swedish nationwide register data. We
      studied future work disability days (mean net days of sick leave and disability
      pension per month) among all individuals with a new sick-leave spell due to
      depressive episode (ICD-10 F32) >= 21 days during the first 6 months of 2010 (n =
      10,327). Using group-based trajectory modeling, we identified work disability
      trajectories for the following 13 months. BIC value, group sizes, and average
      group probability were used to determine number of trajectories. Sociodemographic
      and morbidity characteristics were compared by chi2 tests. Results We identified
      six trajectories of work disability: "decrease to 0 after 4 months" (43% of the
      cohort); "decrease to 0 after 9 months" (22%); "constant high" (11%); "decrease,
      then high increase" (9%); "slow decrease" (9%); and "decrease, then low increase"
      (6%). Those in the groups "constant high" and "decrease then high increase" were
      older and had the highest proportion with sick leave the year before. Conclusion
      A majority of the cohort (65%) had no work disability by the end of follow up.
      Sociodemographic and morbidity characteristics differed between trajectory groups
      among people on sick leave due to a depressive episode.

PMID- 29368030
TI  - Influence of family on expected benefits of complementary and alternative
      medicine (CAM) in cancer patients.
AB  - BACKGROUND: Cancer patients often use complementary and alternative medicine
      (CAM) based on recommendations from family. However, the relationship between
      family endorsement of CAM and the patient's expectation of its benefits has never
      been quantified. METHODS: Between 2010 and 2011, we conducted a cross-sectional
      survey study among patients with a diagnosis of cancer recruited from thoracic,
      breast, and gastrointestinal medical oncology clinics at a single academic cancer
      center. We performed multivariate linear regression analyses to evaluate the
      relationship between perceived family endorsement of and expected benefits from
      CAM, adjusting for covariates. RESULTS: Among the 962 participants, 303 (31.3%)
      reported family endorsement of CAM use. Younger patients and those who had
      college or higher education were more likely to report family endorsement (both p
      < 0.05). Patients with family support had expectation scores that were 15.9
      higher than patients without family support (coefficient 15.9, 95% CI 13.5, 18.2,
      p < 0.001). Participants with family encouragement of CAM use were also more
      likely to expect CAM to cure their cancer (12 vs. 37%) and prolong their life (24
      vs. 61%). These relationships remained highly significant after adjusting for
      covariates). CONCLUSIONS: Family endorsement of CAM use is strongly associated
      with patient expectation of its clinical efficacy, including expectations for
      cure and improved survival. These findings underscore the importance of including
      family in counseling and education on CAM use in order to achieve realistic
      patient expectations, maximize benefits, and avoid potential medical adverse
      effects through herb-drug interactions or rejections of conventional care.

PMID- 29368031
TI  - Efficacy of Partial- Versus Full-Sling Acellular Dermal Matrix Use in Implant
      Based Breast Reconstruction: A Head-to-Head Comparison.
AB  - BACKGROUND: Acellular dermal matrix (ADM), popularly used in tissue expander
      based breast reconstruction, is applied either as a partial or full sling, but
      without any consensus regarding which method of application produces better
      outcomes. We aimed to compare the outcomes between two patient groups who
      underwent tissue expander-based breast reconstruction using these techniques.
      METHODS: A retrospective review was conducted for consecutive patients who
      underwent immediate two-stage implant-based breast reconstruction using ADM
      between January 2013 and June 2016. They were categorized into two cohorts:
      cohort 1 included patients in whom ADM was applied using the partial-sling
      technique, insetting it obliquely after releasing the pectoralis major muscle
      from its costal origin, and cohort 2 included those who underwent a full-sling
      technique, insetting it transversely after releasing the muscle from its costal
      and lower sternal origin. Postoperative complications and aesthetic outcomes were
      compared between the two groups. RESULTS: We analysed 329 cases (167 in cohort 1
      and 162 in cohort 2) with similar baseline characteristics in both cohorts.
      Reconstruction failure occurred in 2.4% of overall patients. The rates of each
      and overall acute complications did not differ significantly between the cohorts.
      Cohort 2 showed significantly lower rates of tissue expander displacement and
      malposition following the first-stage operation and rippling following the second
      stage operation, differences that retained the influences in multivariate
      analyses. Higher aesthetic scores were obtained in cohort 2. CONCLUSION: Using
      the full-sling ADM might reduce unintended migration of prostheses and enable
      proper tissue expansion, resulting in better overall outcomes without increasing
      morbidities. LEVEL OF EVIDENCE III: This journal requires that authors assign a
      level of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 29368032
TI  - Enhanced production of anti-PD1 antibody in CHO cells through transient co
      transfection with anti-apoptotic genes Bcl-x L and Mcl-1.
AB  - Apoptosis has a negative impact on the cell survival state during cell
      cultivation. To optimize mammalian cell culture for production of
      biopharmaceuticals, one of the important approaches is to extend cell life
      through over-expression of anti-apoptotic genes. Here, we reported a cost
      effective process to enhance cell survival and production of an antibody through
      transient co-transfection with anti-apoptotic genes Bcl-x L or Mcl-1 in Chinese
      hamster ovary (CHO) cells with polyethylenimine (PEI). Under the optimal
      conditions, it showed reduced levels of apoptosis and improved cell viability
      after co-transfected with Bcl-x L or Mcl-1. The overall production yield of the
      antibody anti-PD1 increased approximately 82% in CHO cells co-transfected with
      Bcl-x L , and 34% in CHO cells co-transfected with Mcl-1. This work provides an
      effective way to increase viability of host cells through delaying apoptosis
      onset, thus, raise production yield of biopharmaceuticals without the process of
      generating stable cell lines and subsequent screening.

PMID- 29368033
TI  - Development and performance of npde for the evaluation of time-to-event models.
AB  - PURPOSE: Normalised prediction distribution errors (npde) are used to graphically
      and statistically evaluate mixed-effect models for continuous responses. In this
      study, our aim was to extend npde to time-to-event (TTE) models and evaluate
      their performance. METHODS: Let V denote a dataset with censored TTE
      observations. The null hypothesis (H0) is that observations in V can be described
      by model M. We extended npde to TTE models using imputations to take into account
      censoring. We then evaluated their performance in terms of type I error and power
      to detect model misspecifications for TTE data by means of a simulation study
      with different sample sizes. RESULTS: Type I error was found to be close to the
      expected 5% significance level for all sample sizes tested. The npde were able to
      detect misspecifications in the baseline hazard as well as in the link between
      the longitudinal variable and the survival function. The ability to detect model
      misspecifications increased as the difference in the shape of the survival
      function became more apparent. As expected, the power also increased as the
      sample size increased. Imputing the censored events tended to decrease the
      percentage of rejections. CONCLUSIONS: We have shown that npde can be readily
      extended to TTE data and that they perform well with an adequate type I error.

PMID- 29368034
TI  - Transgenerational Effects of Toxicants: An Extension of the Daphnia 21-day
      Chronic Assay?
AB  - The assessment of transgenerational effects should be incorporated in standard
      chronic toxicity protocols for the sake of a realistic extrapolation of
      contaminant effects to the population level. We propose a simple add-on to the
      standard 21-day chronic Daphnia magna assay, allowing the assessment of the
      reproductive performance of the offspring (F1 generation) born from the first
      clutch of the parental (F0) generation. The extended generational assay was
      performed simultaneously with the standard reproduction assay. With this design,
      we evaluated the lethal, reproductive, and transgenerational effects of four
      widespread and extensively used substances: a biocide/anti-fouling (copper
      sulphate), an industrial oxidizing agent (potassium dichromate), a pharmaceutical
      (paracetamol), and a quaternary ammonium compound (benzalkonium chloride).
      Benzalkonium chloride was the most toxic in terms of lethality, whereas
      paracetamol, copper sulphate, and potassium dichromate caused deleterious effects
      in the reproductive performance of exposed D. magna. Adverse effects in the
      fitness of the daughter (F1) generation were observed in the case of maternal
      exposure to paracetamol and copper sulphate, although they were not very
      pronounced. These findings highlight the usefulness of our approach and reinforce
      the view-shared by other authors-of the need for a generalised formal assessment
      of the transgenerational effects of pollutants.

PMID- 29368035
TI  - Alteration of putaminal fractional anisotropy in Parkinson's disease: a
      longitudinal diffusion kurtosis imaging study.
AB  - PURPOSE: In Parkinson's disease (PD), pathological microstructural changes occur
      that may be detected using diffusion magnetic resonance imaging (dMRI). However,
      there are few longitudinal studies that explore the effect of disease progression
      on diffusion indices. METHODS: We prospectively included 76 patients with PD and
      38 healthy controls (HC), all of whom underwent diffusion kurtosis imaging (DKI)
      as part of the prospective Swedish BioFINDER study at baseline and 2 years later.
      Annualized rates of change in DKI parameters, including fractional anisotropy
      (FA), mean diffusivity (MD), and mean kurtosis (MK), were estimated in the gray
      matter (GM) by placing regions of interest (ROIs) in the basal ganglia and the
      thalamus, and in the white matter (WM) by tract-based spatial statistics (TBSS)
      analysis. RESULTS: When adjusting for potential confounding factors (age, gender,
      baseline-follow-up interval, and software upgrade of MRI scanner), only a
      decrease in FA in the putamen of PD patients (beta = - 0.248, P < .01) over 2
      years was significantly different from the changes observed in HC over the same
      time period. This 2-year decrease in FA in the putamen in PD correlated with
      higher L-dopa equivalent dose at baseline (Spearman's rho = .399, P < .0001).
      CONCLUSION: The study indicates that in PD microstructural changes in the putamen
      occur selectively over a 2-year period and can be detected with DKI.

PMID- 29368036
TI  - Transatrial repair of post-infarction ventricular septal defect.
AB  - A 72-year-old woman presented with a post-infarction ventricular septal defect,
      presumably within 10 days after the onset of acute myocardial infarction. An
      emergency surgery was performed because of hemodynamic instability. Using the
      sandwich patch technique, we approached the posteriorly oriented defect through a
      right atriotomy and detached tricuspid valve. By avoiding either left or right
      ventriculotomy, additional damage to the already infarcted ventricle and risk of
      bleeding were avoided. The patient showed an uneventful postoperative recovery,
      with no residual shunt detected. A transatrial approach combined with a sandwich
      patch technique is a good alternative in cases where the pathological anatomy is
      suitable.

PMID- 29368037
TI  - Mycoplasma hominis impacts gene expression in Trichomonas vaginalis.
AB  - In Europe, up to 90% of isolated Trichomonas vaginalis strains are naturally
      infected with Mycoplasma hominis, a facultative pathogen of the human genital
      tract. The consequences of this endosymbiosis are not yet well understood. The
      aim of the current study was to evaluate the impact of natural and artificial
      infections with M. hominis on the RNA expression levels of metronidazole
      susceptibility-associated genes of T. vaginalis. Three T. vaginalis strains
      (TVSS10-, TVSS25-, G3) without M. hominis, as well as the same strains naturally
      (TVSS10+, TVSS25+) and artificially (G3-MhSS25, TVSS25-MhSS25) infected with M.
      hominis, were investigated for their expression profiles of three genes
      associated with metronidazole resistance (ferredoxin, flavin reductase 1 and
      pyruvate:ferredoxin oxidoreductase). The minimal inhibitory concentrations (MICs)
      of metronidazole were evaluated for all combinations and the respective M.
      hominis-free T. vaginalis strains were used as controls. The sole presence of M.
      hominis led to a down-regulation of metronidazole susceptibility-associated genes
      in all T. vaginalis strains tested. Interestingly, the effect was more prominent
      in the artificial symbioses. Moreover, a twofold enhancement of metronidazole
      tolerability was observed in three infected T. vaginalis strains, compared to the
      respective strains without M. hominis. In conclusion, M. hominis had an impact on
      gene expression in all T. vaginalis strains and on metronidazole MIC in all but
      one strain tested.

PMID- 29368038
TI  - Green drugs in the fight against Anisakis simplex-larvicidal activity and
      acetylcholinesterase inhibition of Origanum compactum essential oil.
AB  - Anisakiasis is a fish-borne parasitic disease caused by the consumption of raw or
      undercooked fish, as well as cephalopods, contaminated by third instar larvae
      (L3) of species belonging to the genus Anisakis (Anisakidae). Origanum compactum
      is a small herbaceous aromatic plant endemic to Spain and Morocco. In Morocco,
      the plant is used under infusion to treat heart diseases and intestinal pains or
      as preservative for foodstuffs. This is the first time that the O. compactum
      essential oil is tested against the parasitic nematode Anisakis simplex. The
      phytochemical analysis by GC-MS revealed carvacrol (50.3%) and thymol (14.8%) as
      the major oil constituents. The essential oil and its major constituents
      carvacrol and thymol were tested against A. simplex L3 larvae isolated from blue
      whiting fish (Micromesistius poutassou). A. simplex mortality (%) after 24 and 48
      h of treatment at 1 MUl/ml was 100%, with a low LD50 compared with other
      essential oils and extracts, and the penetration in the agar assay was also
      reduced, if compared with control wells. The oil, as well as its major
      constituents, demonstrated a dose-dependent larvicidal activity. Inhibition of
      the enzyme acetylcholinesterase through a colorimetric assay in 96-well plates
      was used to elucidate the pharmacological mechanism as this enzyme plays a key
      role in nematodes neuromuscular function. Interestingly, O. compactum essential
      oil, carvacrol and thymol inhibited the enzyme, confirming that this could be one
      of the mechanisms involved in the anthelmintic activity. To the best of our
      knowledge, this is the first time that O. compactum essential oil is reported as
      a larvicidal agent against A. simplex L3 larvae.

PMID- 29368039
TI  - Assessment of Subtle Changes in Diabetes-Associated Arteriosclerosis using
      Photoplethysmographic Pulse Wave from Index Finger.
AB  - Distortions in macro- and microcirculation are principal contributors to diabetes
      associated complications. This study aimed at investigating the validity of
      applying non-invasive photoplethysmographic (PPG) waveform parameters in
      detecting diabetes-induced subtitle changes in arterial stiffness. Between July
      2009 and October 2010, totally 94 middle-aged and elderly subjects were recruited
      including 48 without diabetes (Group 1) and 46 with the disease (Group 2).
      Demographic (i.e., age, gender), anthropometric (body-mass index), biochemical
      (i.e., glycated hemoglobin concentration), and hemodynamic (i.e., systolic blood
      pressure, heart rate) parameters were obtained. Crest time (CT) and crest time
      ratio (CTR) computed from PPG signals acquired from left index finger were
      compared with left index finger pulse wave velocity (PWVfinger) obtained from six
      channel ECG-PWV system to investigate the differences between the two groups and
      the associations of these indices with the parameters of testing subjects.
      Significant difference was only noted in CTR between the two groups (P < 0.005).
      Despite correlation of both CT and CTR with age, only CTR demonstrated
      significant associations with hemodynamic parameters. CTR could differentiate
      diabetic patients from healthy individuals despite absence of difference in
      arterial stiffness assessed by conventional PWV, highlighting its superior
      sensitivity to subtle changes in diabetes-associated arteriosclerosis.

PMID- 29368040
TI  - Bilateral lateral rectus recession versus unilateral recession resection for
      basic intermittent exotropia: a meta-analysis.
AB  - OBJECTIVE: To compare the outcomes between bilateral lateral rectus recession
      (BLR) and unilateral recession resection (R&R) procedures in the treatment of
      basic intermittent exotropia. METHODS: Databases from Medline, Embase, Web of
      Science and the Cochrane Register of Controlled Trials were searched prior to
      June 2, 2017. From these searches, three eligible randomized studies and three
      retrospective cohort trials, which compared conventional BLR versus R&R procedure
      were identified. Differences observed between these two interventions (BLR versus
      R&R) were expressed as odds ratio (OR) and 95% confidence intervals (CI). The
      data on rates of success, recurrence, and overcorrection were pooled and analyzed
      using a random-effects model. RESULTS: Our findings, as generated from the pooled
      estimates, suggested that success rates for the R&R procedure were significantly
      greater than that of BLR (OR, 0.50; 95% CI, 0.31-0.79; P = 0.003) and patients
      subjected to the BLR procedure were more likely to be recurrent (OR, 2.44; 95%
      CI, 1.17-5.10; P = 0.02). No statistically significant differences in the
      combined results for overcorrection rates were present between the BLR and R&R
      procedures (OR, 0.85; 95% CI, 0.32-2.28; P = 0.75). CONCLUSION: The overall
      findings from this meta-analysis indicated that the conventional R&R procedure is
      associated with higher success rates and lower recurrence rates in patients with
      basic intermittent exotropia.

PMID- 29368041
TI  - Detailed analysis of retinal morphology in patients with diabetic macular edema
      (DME) randomized to ranibizumab or triamcinolone treatment - reply to the letter
      to the editor.

PMID- 29368042
TI  - Primary Ciliary Dyskinesia Due to Microtubular Defects is Associated with Worse
      Lung Clearance Index.
AB  - PURPOSE: Primary ciliary dyskinesia (PCD) is characterised by repeated upper and
      lower respiratory tract infections, neutrophilic airway inflammation and
      obstructive airway disease. Different ultrastructural ciliary defects may affect
      lung function decline to different degrees. Lung clearance index (LCI) is a
      marker of ventilation inhomogeneity that is raised in some but not all patients
      with PCD. We hypothesised that PCD patients with microtubular defects would have
      worse (higher) LCI than other PCD patients. METHODS: Spirometry and LCI were
      measured in 69 stable patients with PCD. Age at testing, age at diagnosis,
      ethnicity, ciliary ultrastructure, genetic screening result and any growth of
      Pseudomonas aeruginosa was recorded. RESULTS: Lung clearance index was more
      abnormal in PCD patients with microtubular defects (median 10.24) than those with
      dynein arm defects (median 8.3, p = 0.004) or normal ultrastructure (median 7.63,
      p = 0.0004). Age is correlated with LCI, with older patients having worse LCI
      values (p = 0.03, r = 0.3). CONCLUSION: This study shows that cilia microtubular
      defects are associated with worse LCI in PCD than dynein arm defects or normal
      ultrastructure. The patient's age at testing is also associated with a higher
      LCI. Patients at greater risk of obstructive lung disease should be considered
      for more aggressive management. Differences between patient groups may
      potentially open avenues for novel treatments.

PMID- 29368043
TI  - Comparison of Urticaria Activity Score Over 7 Days (UAS7) Values Obtained from
      Once-Daily and Twice-Daily Versions: Results from the ASSURE-CSU Study.
AB  - BACKGROUND: The Urticaria Activity Score summed over 7 days (UAS7) assesses the
      itch severity and hive count in chronic spontaneous urticaria (CSU) using once-
      or twice-daily diary-based documentation. OBJECTIVE: The aim of this study was to
      evaluate the comparability of twice-daily versus once-daily versions of the UAS
      and the resulting UAS7 values. METHODS: Data came from the ASSURE-CSU study. The
      twice-daily and once-daily UAS7 was calculated from morning and evening ratings,
      as well as from exact 24-h evening ratings of hive count and itch severity,
      respectively. Three UAS7 scores were computed: UAS7 twice daily (UAS7TD), UAS7
      once daily for maximum itch (UAS7OD1MAX), and UAS7 once daily for average itch
      (UAS7OD2AVG). UAS7 values were assigned to five score bands (0, 1-6, 7-15, 16-27,
      28-42), reflecting urticaria-free to severe disease activity. The score values
      and score band ratios of the UAS7TD and UAS7OD versions were compared and
      assessed for correlation by weighted Cohen's kappa statistics. RESULTS: Data from
      614 patients were analyzed. All three versions of the UAS7 yielded very similar
      results, with a mean (standard deviation) UAS7TD, UAS7OD1MAX, and UAS7OD2AVG of
      17.3 (10.49), 17.7 (8.90), and 16.2 (8.68), respectively. Correlation
      coefficients between UAS7TD and UAS7OD1MAX, UAS7TD and UAS7OD2AVG, and UAS7OD1MAX
      and UAS7OD2AVG were 0.94, 0.95, and 0.99, respectively, showing very high
      positive pairwise correlation. The weighted kappa coefficient, kappa (95%
      confidence interval) was 0.78 (0.75-0.82) for UAS7TD versus UAS7OD1MAX, and 0.82
      (0.78-0.85) for UAS7TD versus UAS7OD2AVG, demonstrating substantial agreement.
      CONCLUSIONS: The once- and twice-daily UAS7 scores were highly consistent,
      supporting the use of either version when evaluating CSU activity.

PMID- 29368044
TI  - Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in
      regulating endosomal protein sorting and amyloid precursor protein processing.
AB  - The processing of amyloid precursor protein (APP) to the neurotoxic pro
      aggregatory Abeta peptide is controlled by the mechanisms that govern the
      trafficking and localisation of APP. We hypothesised that genes involved in
      endosomal protein sorting could play an important role in regulating APP
      processing and, therefore, analysed ~ 40 novel endosome-to-Golgi retrieval genes
      previously identified in a genome-wide siRNA screen. We report that phospholipase
      D3 (PLD3), a type II membrane protein, functions in endosomal protein sorting and
      plays an important role in regulating APP processing. PLD3 co-localises with APP
      in endosomes and loss of PLD3 function results in reduced endosomal tubules,
      impaired trafficking of several membrane proteins and reduced association of
      sortilin-like 1 with APP.

PMID- 29368045
TI  - Long-term survivorship of stemless anatomical shoulder replacement.
AB  - PURPOSE: Like in many other joints, current shoulder replacement designs aim at
      bone preservation. According to the literature available, stemless total shoulder
      arthroplasty (TSA) compares favourably with stemmed designs in terms of function
      and survivorship of the implant. However, long-term results of stemless shoulder
      arthroplasty are still missing. Therefore, the aim of the present study was to
      evaluate long-term results of stemless anatomical TSA. METHODS: Between 2006 and
      2009, 51 shoulders in 46 patients were resurfaced using the Biomet Total
      Evolutive Shoulder System (TESS). Thirty-one shoulders in 26 patients who were
      aged 66.7 +/- 10.0 (range 34-82) years were available for review at a mean follow
      up of 94.7 +/- 11.3 (76-124) months. RESULTS: The implant survival rate was 93.5%
      at eight years. The overall revision rate of the TESS implant was 9.7%.
      Radiolucent lines were found on the glenoid side of the TESS arthroplasty in
      90.9% of the cases. All stemless humeral corolla implants showed solid fixation
      at follow-up. Clinical scores significantly improved at long-term follow-up (VAS
      from 8.1 +/- 0.9 to 1.0 +/- 1.2, p < 0.001; Quick-DASH from 67.9 +/- 13.5 to 18.7
      +/- 16.5, p < 0.001 and Constant score from 14.7 +/- 6.1 to 68.8 +/- 13.2, p <
      0.001). CONCLUSIONS: Stemless TSA has stood the test of time at eight years in
      terms of clinical scores, radiographic loosening, complication rates and implant
      survivorship.

PMID- 29368046
TI  - Current evidence does not support systematic antibiotherapy prior to joint
      arthroplasty in patients with asymptomatic bacteriuria-a meta analysis.
AB  - BACKGROUND: Many orthopaedic surgeons worry about asymptomatic bacteriuria (ASB)
      as a possible risk factor for prosthetic joint infection (PJI). However,
      available evidence establishing a direct link between ASB and PJI is limited.
      This meta-analysis aimed to investigate whether ASB is a factor for PJI and
      whether pre-operative antibiotic treatment shows benefit. METHOD: We
      systematically searched major databases such as PubMed, Web of Science, the
      Cochrane Library and EMBASE for studies. Risk ratio (RR) was calculated for
      included studies that reported raw counts with 95% confidence interval (CI).
      RESULTS: Five studies involved 3588 joint arthroplasties and 441 cases of ASB
      (overall incidence 12.3%). Compared with the control group, PJI was more common
      in both patients in the ASB group (RR = 2.87; 95% CI, 1.65-5.00). But in all five
      studies, the micro-organisms isolated from PJI and urine cultures were not the
      same. Three of the five studies reported that the antibiotic treated the ASB
      prior to joint arthroplasty and compared the untreated ASB group.There was no
      significant difference between groups (RR = 0.89; 95% CI, 0.36-2.20). DISCUSSION:
      PJI occurring via the haematogenous route from the genitourinary tract harbouring
      bacteria in ASB is impossible. Pre-operative antibiotic treatment has no benefit.
      A plausible explanation could be an indicator of frailty and increased
      susceptibility to infection. CONCLUSIONS: ASB increased the risk of PJI in the
      meta-analysis. However, current evidence does not support systematic
      antibiotherapy prior to joint arthroplasty and screening for ASB.

PMID- 29368047
TI  - The impact of nTMS mapping on treatment of brain AVMs.
AB  - BACKGROUND: The treatment of brain arteriovenous malformations (BAVMs) is still
      contrarily discussed. Despite the debatable results of the ARUBA trial, most
      BAVMs still require treatment depending on the Spetzler-Martin (SM) grading.
      Since size is measurable and venous drainage is visible, the determination of
      eloquence is comparably crucial but not fully objective. The present bicentric
      cohort study aims to examine the influence of preoperative navigated transcranial
      magnetic stimulation (nTMS) motor and language mapping data on decision-making
      for or against surgical treatment of BAVMs. METHODS: The influence of data from
      nTMS on decision-making for or against treatment of BAVMs was examined by
      confirming/falsifying presumed motor or language eloquence. RESULTS: The results
      of nTMS mappings changed the SM grading in nine cases. In six cases, the SM
      grading changed to a lower grade (= falsified eloquence); in three cases, the SM
      grading changed to a higher grade due to nTMS mappings (= unexpected eloquence).
      Out of all 34 cases, indication for surgery was supported by nTMS mappings in 15
      cases (7 motors, 8 languages). In six cases, the decision against surgery was
      made based on nTMS mappings (three motors, three languages). CONCLUSION: In 21 of
      34 cases (62%), nTMS was a supportive argument. We could show that nTMS motor and
      language data can be used for a more objective decision-making regarding the
      treatment of BAVMs and for a more detailed SM grading regarding the rating of
      eloquence.

PMID- 29368048
TI  - A systematic review of psychological treatments for clinical anxiety during the
      perinatal period.
AB  - Maternal anxiety is common during the perinatal period, and despite the negative
      outcomes of anxiety on the mother and infant, its treatment has received limited
      attention. This paper describes the first review of psychological interventions
      for clinical anxiety during the perinatal period. A systematic search was carried
      out of six electronic databases. Five studies which evaluated psychological
      interventions for clinical anxiety in perinatal women were identified. Of the
      five studies included, four were open trials and one was a randomised controlled
      trial. Three studies evaluated group-based interventions; one study evaluated an
      online-delivered intervention; and one study a combined pharmacologic
      psychological intervention. All participants demonstrated significant reductions
      in anxiety symptom severity from pre- to post-treatment. However, this review was
      limited to published literature evaluating treatments for clinical anxiety in
      perinatal women, which may have excluded important intervention studies and
      prevention programs, and unpublished literature. This review identifies an area
      of research that needs urgent attention, as very few studies have evaluated
      psychological treatments for perinatal anxiety. The studies included in this
      review demonstrate that symptoms of anxiety during the perinatal period appear to
      improve during treatment. Future research is needed to establish the efficacy of
      perinatal anxiety interventions in randomised controlled trials, whether
      reductions persist long term and whether benefits extend to other outcomes for
      the mother, infant and family.

PMID- 29368049
TI  - [Orthopaedics and the law].

PMID- 29368050
TI  - Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations,
      and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients
      with advanced solid tumors.
AB  - PURPOSE: Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3
      testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. To
      optimize its dosing conditions, a number of clinical pharmacology characteristics
      were examined in this multi-center trial in patients with advanced solid tumors.
      METHOD: This was an open-label, single-dose, crossover clinical pharmacology
      study investigating the effects of strong CYP3A4 inhibition with posaconazole
      (Part 1), two new oral formulations (Part 2), as well as high-energy/high-fat and
      low-energy/low-fat meals (Part 3) on the relative bioavailability of idasanutlin.
      After completing Part 1, 2, or 3, patients could have participated in an optional
      treatment with idasanutlin. Clinical endpoints were pharmacokinetics (PK),
      pharmacodynamics (PD) of MIC-1 elevation (Part 1 only), and safety/tolerability.
      RESULTS: The administration of posaconazole 400 mg BID * 7 days with idasanutlin
      800 mg resulted in a slight decrease (7%) in Cmax and a modest increase (31%) in
      AUC for idasanutlin, a marked reduction in Cmax (~ 60%) and AUC0 (~ 50%) for M4
      metabolite, and a minimal increase (~ 24%) in serum MIC-1 levels. Cmax and AUC
      were both 45% higher for the SDP formulation. While the low-fat meal caused a
      less than 20% increase in all PK exposure parameters with the 90% CI values just
      outside the upper end of the equivalence criteria (80-125%), the high-fat meal
      reached bioequivalence with dosing under fasting. CONCLUSION: In patients with
      solid tumors, multiple doses of posaconazole, a strong CYP3A4 inhibitor,
      minimally affected idasanutlin PK and PD without clinical significance. The SDP
      formulation improved rBA/exposures by ~ 50% without major food effect.

PMID- 29368051
TI  - Role of immunotherapy in bladder cancer: past, present and future.
AB  - As research focus in oncology has recently shifted from oral targeted therapy to
      immunomodulation, the era of successful drug development in bladder cancer has
      just begun. This has led to unprecedented approval of five immunotherapeutic
      agents by regulatory agencies for metastatic bladder cancer within a span of 12
      months. With an initial triumph of anti-programmed cell death-1 (anti-PD-1) and
      anti-programmed cell death ligand-1 (anti-PDL-1) drugs, ongoing efforts are aimed
      at identification and validation of new druggable immune targets to consolidate
      the initial gains. In this paper, we review the role of immunotherapy in the
      treatment of bladder cancer as well as the various emerging immunotherapeutic
      agents and their possible use in bladder cancer.

PMID- 29368053
TI  - Cellular complexity in subcortical white matter: a distributed control circuit?
AB  - The subcortical white matter (SWM) has been traditionally considered as a site
      for passive-neutral-information transfer through cerebral cortex association and
      projection fibers. Yet, the presence of subcortical neuronal and glial
      "interstitial" cells expressing immunolabelled neurotransmitters/neuromodulators
      and synaptic vesicular proteins, and recent immunohistochemical and
      electrophysiological observations on the rat visual cortex as well as interactive
      regulation of myelinating processes support the possibility that SWM nests
      subcortical, regionally variable, distributed neuronal-glial circuits, that could
      influence information transfer. Their hypothetical involvement in regulating the
      timing and signal transfer probability at the SWM axonal components ought to be
      considered and experimentally analysed. Thus, the "interstitial" neuronal cells
      associated with local glial cells-traditionally considered to be vestigial and
      functionally inert under normal conditions, they may well turn to be critical in
      regulating information transfer at the SWM.

PMID- 29368052
TI  - Different neural substrates for precision stepping and fast online step
      adjustments in youth.
AB  - Humans can navigate through challenging environments (e.g., cluttered or uneven
      terrains) by modifying their preferred gait pattern (e.g., step length, step
      width, or speed). Growing behavioral and neuroimaging evidence suggests that the
      ability to modify preferred step patterns requires the recruitment of cognitive
      resources. In children, it is argued that prolonged development of complex gait
      is related to the ongoing development of involved brain regions, but this has not
      been directly investigated yet. Here, we aimed to elucidate the relationship
      between structural brain properties and complex gait in youth aged 9-18 years. We
      used volumetric analyses of cortical grey matter (GM) and whole-brain voxelwise
      statistical analyses of white matter (WM), and utilized a treadmill-based
      precision stepping task to investigate complex gait. Moreover, precision stepping
      was performed on step targets which were either unperturbed or perturbed (i.e.,
      unexpectedly shifting to a new location). Our main findings revealed that larger
      unperturbed precision step error was associated with decreased WM microstructural
      organization of tracts that are particularly associated with attentional and
      visual processing functions. These results strengthen the hypothesis that
      precision stepping on unperturbed step targets is driven by cortical processes.
      In contrast, no significant correlations were found between perturbed precision
      stepping and cortical structures, indicating that other (neural) mechanisms may
      be more important for this type of stepping.

PMID- 29368054
TI  - New keratinolytic bacteria in valorization of chicken feather waste.
AB  - There is an increasing demand for cost-effective and ecologically-friendly
      methods for valorization of poultry feather waste, in which keratinolytic
      bacteria present a great potential. Feather-degrading bacteria were isolated from
      living poultry and a single strain, identified as Kocuria rhizophila p3-3,
      exhibited significant keratinolytic properties. The bacterial strain effectively
      degraded up to 52% of chicken feathers during 4 days of culture at 25  degrees C.
      Zymographic analysis revealed the presence of two dominating proteolytic enzymes
      in the culture fluid. Culture conditions were optimized in order to maximize the
      liberation of soluble proteins and free amino acids. A two-step procedure was
      used, comprising a Plackett-Burman screening design, followed by a Box-Behnken
      design. Concentration of feather substrate, MgSO4 and KH2PO4 were the most
      influential parameters for the accumulation of soluble proteins in culture K.
      rhizophila p3-3, while feathers and MgSO4 also affected the concentration of
      amino acids. The resultant raw hydrolysate supernatant, prior to and after
      additional treatments, was rich in phenylalanine, histidine, arginine and
      aspartic acid. Additionally the hydrolysate exhibited radical-scavenging activity
      and ferric reducing power.

PMID- 29368055
TI  - Enhancement of docosahexaenoic acid (DHA) production from Schizochytrium sp. S31
      using different growth medium conditions.
AB  - Schizochytrium species is one of the most studied microalgae for production of
      docosahexaenoic acid (DHA) which is an omega-3 fatty acid with positive effects
      for human health. However, high cost and low yield in production phase makes
      optimization of cultivation process inevitable. We focus on the optimization of
      DHA production using Schizochytrium sp. using different media supplements;
      glucose, fructose and glycerol as carbon variants, proteose peptone and tryptone
      as nitrogen variants. The highest biomass (5.61 g/L) and total fatty acid yield
      (1.74 g/L) were obtained in proteose peptone medium which was used as the
      alternative nitrogen source instead of yeast extract. The highest DHA yield (0.40
      g/L) was achieved with glycerol as the carbon source although it had the second
      lowest biomass production after ethanol containing medium. Ethanol, as an
      alternative carbon source and a precursor for acetyl-CoA, increased DHA
      percentage in total lipid content from 29.94 to 40.04% but decreasing the biomass
      drastically. Considering different carbon and nitrogen sources during cultivation
      of Schizochytrium sp. will improve DHA production. Combination of proteose
      peptone and glycerol as nitrogen and carbon sources, respectively, and addition
      of ethanol with a proper timing will be useful to have higher DHA yield.

PMID- 29368056
TI  - External confirmation and exploration of the Kigali modification for diagnosing
      moderate or severe ARDS.

PMID- 29368057
TI  - Understanding thrombotic microangiopathies in children.

PMID- 29368058
TI  - Ecological and biogeographical drivers of freshwater green algae biodiversity:
      from local communities to large-scale species pools of desmids.
AB  - Dispersal limitation, niche-based processes as well as historical legacies shape
      microbial biodiversity, but their respective influences remain unknown for many
      groups of microbes. We analysed metacommunity structure and functional trait
      variation in 148 communities of desmids, freshwater green algae, distributed
      throughout Europe. We delineated biogeographic modules for both taxa and sites
      using bipartite network analysis given that the taxa of a module co-occurred more
      often than expected by chance in sites of the same module. The network analysis
      distinguished two main acidic and neutral habitats, reflecting environmental
      filtering, and within each habitat separated species pools with distinct
      geographic locations, representing a plausible influence of historical
      biogeography. The geographic differentiation was consistent with a hypothesis of
      glacial refugia on Atlantic coast. Distance decay in community composition in
      addition to environmental influence further suggested a role of dispersal
      limitation. Next, we quantified the variation in cell volume and surface-to
      volume of taxa within and among communities, to examine morphological and
      physiological adaptations of desmids in varying environments. Communities from
      continental climate contained larger desmids. Conversely, we found a functional
      convergence of smaller, fast-growing, desmids in oceanic regions. Overall, our
      findings suggest that niche-based processes, dispersal limitation, and historical
      legacy together drive the distribution and structure of desmid communities.
      Combining trait- and network-based analyses can resolve long-lasting questions in
      microbial ecology and biogeography, and could be successfully used in macrobial
      ecology too.

PMID- 29368059
TI  - Lessons Learned in Clinical Research Recruitment of Immigrants and Minority Group
      Members with First-Episode Psychosis.
AB  - Recruitment of immigrants and racial and ethnic minorities with first-episode
      psychosis (FEP) for research studies presents numerous challenges. We describe
      methods used to recruit 43 U.S. Latinos with FEP and their family caregivers (n =
      41) participating in a study to reduce duration of untreated psychosis. A key
      challenge was that patients were not continuing treatment at an outpatient
      clinic, as initially expected. To facilitate identification of patients prior to
      outpatient care, we collaborated with clinic and hospital administrators. Many
      patients and families were grappling with the aftermath of a hospitalization or
      adjusting to a diagnosis of a serious mental illness. A considerable amount of
      time was devoted to addressing participants' concerns and when possible,
      facilitating needed services. Our experience underscores the importance of
      establishing long-term relationships through multiple contacts with patients,
      families, and stakeholders to address recruitment barriers among underserved
      groups with FEP.

PMID- 29368060
TI  - Does the Brain's Reward Response Occur Even Without Actual Reward? A Response to
      Fielding et al. (2017).
AB  - A recent paper by Fielding et al. (J Gamb Stud, 2017) argued that the brain's
      reward response could occur without the presentation of actual reward. We suggest
      that since (a) the event-related potentials reported in this paper are atypical
      of the previous literature, and, (b) a simpler account of the data in terms of
      sensitivity to outcome frequency cannot be ruled out, the extent to which the
      brain's reward response can occur without the presentation of actual reward
      should remain an open question.

PMID- 29368061
TI  - Comparative Test Evaluation: Methods and Challenges.
AB  - The present paper has three objectives. First, methods for comparing alternative
      tests for the purpose of replacement of one test with a second presumably
      superior test are described. Second, problems in the interpretation of the
      relevance of different diagnostic thresholds (thresholds of positivity) that
      define who is and who is not a disordered gambler are examined and a potential
      solution offered in the form of a common quantitative measure of the risk of
      being a disordered gambler. Third, alternative methodologies are described as
      potential solutions to the lack of a gold or reference standard in the evaluation
      of new tests.

PMID- 29368063
TI  - Genetic diversity of Orf virus isolated from sheep in Uruguay.
AB  - Orf virus (ORFV) is the etiological agent of contagious ecthyma, a disease widely
      spread in the world that occasionally causes zoonotic infections. This work is
      the first molecular characterization of ORFV in Uruguay, where we analyzed twenty
      one sheep samples, eighteen of which were recovered from thirteen ORFV outbreaks
      that occurred during 2004 to 2011 as well as three strains from a national
      vaccine. Phylogenetic analysis and the derived amino acid sequences from the B2L
      gene suggest that the Uruguayan virus do not form a unique cluster, with most of
      them displaying similarities with worldwide ORFV isolates as well as our vaccine
      strains.

PMID- 29368062
TI  - A comprehensive evaluation of clinicopathologic characteristics, molecular
      features and prognosis in lung adenocarcinoma with solid component.
AB  - PURPOSE: We have reported that solid predominant lung adenocarcinoma according to
      the IASLC/ATS/ERS classification was associated with poor prognosis. However, the
      correlation of solid component with clinicopathological, molecular features, and
      prognosis in all lung adenocarcinoma patients remains unexplored. METHODS:
      Surgically resected lung adenocarcinomas were divided into three groups, solid
      predominant (solid component accounting for at least 50%), solid minor (solid
      component accounting for 5-45%) and solid negative. Patients' clinicopathological
      characteristics, disease free survival (DFS), overall survival (OS) and molecular
      alterations, including EGFR, KRAS, FGFR, etc., were analyzed. RESULTS: Of 1098
      lung adenocarcinomas, 198 were solid predominant, 132 were solid minor, and 768
      were solid negative. Solid positive patients, including solid predominant and
      solid minor, had significantly worse DFS (p < 0.0001) and OS (p < 0.0001)
      compared with solid negative group, so were solid minor patients (both p <
      0.0001). Cox multivariate analysis revealed that solid positive pattern was an
      independent predictor for DFS [hazard ratio (HR) 1.495, 95% confidence interval
      (CI) 1.004-2.233; p = 0.034] and OS [HR 1.561, 95% CI 1.03-2.342; p = 0.016]. The
      frequency of FGFR fusions was significantly higher in solid positive lung
      adenocarcinomas than in solid negative group (1.5 vs. 0.3%, p = 0.048). The
      response rate to EGFR-tyrosine kinase inhibitors (TKIs) was 66.7% in EGFR-mutated
      solid positive patients after recurrence. CONCLUSIONS: This study represents the
      first comprehensive clinical investigation of solid component in lung
      adenocarcinomas, identifying solid positive pattern as an independent poor
      prognostic indicator in lung adenocarcinoma.

PMID- 29368064
TI  - Molecular characterization of a novel rhabdovirus infecting blackcurrant
      identified by high-throughput sequencing.
AB  - A large contig with sequence similarities to several nucleorhabdoviruses was
      identified by high-throughput sequencing analysis from a black currant (Ribes
      nigrum L.) cultivar. The complete genome sequence of this new nucleorhabdovirus
      is 14,432 nucleotides long. Its genomic organization is very similar to those of
      unsegmented plant rhabdoviruses, containing six open reading frames in the order
      3'-N-P-P3-M-G-L-5. The virus, which is provisionally named "black currant
      associated rhabdovirus", is 41-52% identical in its genome nucleotide sequence to
      other nucleorhabdoviruses and may represent a new species in the genus
      Nucleorhabdovirus.

PMID- 29368066
TI  - Outpatient balneological treatment of osteoarthritis in older persons : A
      retrospective study.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of outpatient balneological
      treatment consisting of hydrotherapy and peloid therapy in elderly patients with
      osteoarthritis. METHODS: In this retrospective observational study all patients
      aged >=65 years with any type of osteoarthritis who received balneological
      treatment (hydrotherapy and peloid therapy) at our clinic between 2007 and 2016
      were included. Hydrotherapy was applied as head-out immersion in a tap water pool
      at 36-38  degrees C for 20 min and then peloid therapy was applied as a local
      peloid pack on the painful region or joint at 42-43  degrees C for 20 min, on
      each weekday for 2 weeks. Patients were evaluated before and after the treatment
      and outcome measurements were pain, patient's global assessment, physician's
      global assessment, Western Ontario and McMaster Universities index, Lequesne hip
      index, Waddell index, neck pain and disability scale, and health assessment
      questionnaire. RESULTS: In total, 235 osteoarthritis patients comprising 61
      generalized, 91 knee, 6 hip; 32 lumbar, 12 cervical, 1 foot and 32 hand
      osteoarthritis, were included in the analysis. We found significant improvements
      in pain and function scores in generalized, knee, lumbar, cervical and hand
      osteoarthritis. Patient's global assessment was also improved in all subtypes
      except hip (p = 1.000) and hand (p = 0.132) osteoarthritis subtypes. The majority
      of patients (59.1%) fulfilled the outcome measures in Rheumatology-Osteoarthritis
      Research Society International (OMERACT-OARSI) responder criteria. The treatment
      demonstrated a good safety profile. CONCLUSION: Study results provide initial
      evidence for the potential beneficial effects and safety of outpatient
      balneological treatment (hydrotherapy and peloid therapy) in the management of
      older patients with osteoarthritis. Future randomized controlled studies are
      needed to confirm these results.

PMID- 29368065
TI  - Virological and pathological characterization of an avian H1N1 influenza A virus.
AB  - Gene segments from avian H1N1 influenza A viruses have reassorted with other
      influenza viruses to generate pandemic strains over the past century.
      Nevertheless, little effort has been invested in understanding the
      characteristics of avian H1N1 influenza viruses. Here, we present the genome
      sequence and a molecular and virological characterization of an avian influenza A
      virus, A/wild bird/Korea/SK14/2014 (A/SK14, H1N1), isolated from migratory birds
      in South Korea during the winter season of 2014-2015. Full-genome sequencing and
      phylogenetic analysis revealed that the virus belongs to the Eurasian avian
      lineage. Although it retained avian-receptor binding preference, A/SK14 virus
      also exhibited detectable human-like receptor binding and was able to replicate
      in differentiated primary normal human bronchial epithelial cells. In animal
      models, A/SK14 virus was moderately pathogenic in mice, and virus was detected in
      nasal washes from inoculated guinea pigs, but not in direct-contact guinea pigs.
      Although A/SK14 showed moderate pathogenicity and no evidence of transmission in
      a mammalian model, our results suggest that the dual receptor specificity of
      A/SK14-like virus might allow for a more rapid adaptation to mammals, emphasizing
      the importance of further continuous surveillance and risk-assessment activities.

PMID- 29368068
TI  - Theoretical insight into reaction mechanisms of 2,4-dinitroanisole with hydroxyl
      radicals for advanced oxidation processes.
AB  - The detailed degradation mechanism of an insensitive explosive, 2,4
      dinitroanisole (DNAN), in advanced oxidation processes (AOPs) was investigated
      computationally at the M06-2X/6-311 + G(d,p)/SMD level of theory. Results
      obtained show that the addition-elimination reaction is the dominant mechanism.
      The phenol products formed can continue to be oxidized to benzoquinone radicals
      that are often detected by experiments and may be the initial reactants of ring
      opening reactions. The H-abstraction reaction is an unavoidable competing
      mechanism; the intermediate generated can also undergo the process of addition
      elimination reaction. The nitro departure reaction involves not only hydroxyl
      radical (*OH), but also other active substances (such as *H). More importantly,
      we found that AOP technology can easily degrade DNAN, similar to TNT and DNT.
      Thus, this method is worth trying in experiments. The conclusions of this work
      provide theoretical support for such experimental research. Graphical abstract
      Possible pathways of degradation by *OH radicals in advanced oxidation processes
      (AOPs) of the typical insensitive explosive 2,4-dinitroanisole (DNAN) were
      investigated by density functional theory (DFT) methods. Based on the Gibbs free
      energy barriers and intermediates, the dominant reaction mechanism was
      determined. The conclusions will be helpful in utilizing AOP technology to remove
      DNAN pollution.

PMID- 29368067
TI  - Cilostazol-Loaded Poly(epsilon-Caprolactone) Electrospun Drug Delivery System for
      Cardiovascular Applications.
AB  - PURPOSE: The study discusses the value of electrospun cilostazol-loaded (CIL)
      polymer structures for potential vascular implant applications. METHODS:
      Biodegradable polycaprolactone (PCL) fibers were produced by electrospinning on a
      rotating drum collector. Three different concentrations of CIL: 6.25%, 12.50% and
      18.75% based on the amount of polymer, were incorporated into the fibers. The
      fibers were characterized by their size, shape and orientation. Materials
      characterization was carried out by Fourier Transformed Infrared spectroscopy
      (FTIR), Raman spectroscopy, differential scanning calorimetry (DSC) and X-ray
      diffraction (XRD). In vitro drug release study was conducted using flow-through
      cell apparatus (USP 4). RESULTS: Three-dimensional structures characterized by
      fibers diameter ranging from 0.81 to 2.48 MUm were in the range required for
      cardiovascular application. DSC and XRD confirmed the presence of CIL in the
      electrospun fibers. FTIR and Raman spectra confirmed CIL polymorphic form.
      Elastic modulus values for PCL and the CIL-loaded PCL fibers were in the range
      from 0.6 to 1.1 GPa. The in vitro release studies were conducted and revealed
      drug dissolution in combination with diffusion and polymer relaxation as
      mechanisms for CIL release from the polymer matrix. CONCLUSIONS: The release
      profile of CIL and nanomechanical properties of all formulations of PCL fibers
      demonstrate that the cilostazol loaded PCL fibers are an efficient delivery
      system for vascular implant application.

PMID- 29368069
TI  - Effect of low-level laser therapy on the healing process of donor site in
      patients with grade 3 burn ulcer after skin graft surgery (a randomized clinical
      trial).
AB  - Skin graft is a standard therapeutic technique in patients with deep ulcers, but
      managing donor site after grafting is very important. Although several modern
      dressings are available to enhance the comfort of donor site, using techniques
      that accelerate wound healing may enhance patient satisfaction. Low-level laser
      therapy (LLLT) has been used in several medical fields, including healing of
      diabetic, surgical, and pressure ulcers, but there is not any report of using
      this method for healing of donor site in burn patients. The protocols and
      informed consent were reviewed according to Medical Ethics Board of Shahid
      Beheshti University of Medical Sciences (IR.SBMU.REC.1394.363) and Iranian
      Registry of Clinical Trials (IRCT2016020226069N2). Eighteen donor sites in 11
      patients with grade 3 burn ulcer were selected. Donor areas were divided into 2
      parts, for laser irradiation and control randomly. Laser area was irradiated by a
      red, 655-nm laser light, 150 mW, 2 J/cm2, on days 0 (immediately after surgery),
      3, 5, and 7. Dressing and other therapeutic care for both sites were the same.
      The patients and the person who analyzed the results were blinded. The size of
      donor site reduced in both groups during the 7-day study period (P < 0.01) and
      this reduction was significantly greater in the laser group (P = 0.01). In the
      present study, for the first time, we evaluate the effects of LLLT on the healing
      process of donor site in burn patients. The results showed that local irradiation
      of red laser accelerates wound healing process significantly.

PMID- 29368071
TI  - Correction to: Effect of 1064-nm Q-switched Nd:YAG laser on invasiveness and
      innate immune response in keratinocytes infected with Candida albicans.
AB  - In the published online version of the article, the authors' given and family
      names were incorrectly captured. The corrected names are shown in the author
      group section above.

PMID- 29368070
TI  - Adaptation and micro-structure of Co-Cr alloy maxillary complete denture base
      plates fabricated by selective laser melting technique.
AB  - The purpose of the study was to evaluate the adaptation and micro-structure of Co
      Cr alloy maxillary complete denture base plates fabricated by the selective laser
      melting (SLM) technique. Twenty pairs of edentulous casts were randomly and
      evenly divided into two groups, and manufacturing of the Co-Cr alloy maxillary
      complete denture base was conducted either by the SLM technique or by the
      conventional method. The base-cast sets were transversally sectioned into three
      sections at the distal canines, mesial of the first molars and the posterior
      palatal zone. The gap between the metal base and cast was measured in these three
      sections with a stereoscopic microscope, and the data were analysed using t
      tests. A total of five specimens of 5 mm diameter were fabricated with the Co-Cr
      alloy by SLM and the traditional casting technology. A scanning electron
      microscope (SEM) was used to evaluate the differences in microstructure between
      these specimens. There was no statistical difference between the three sections
      in all four groups (P > 0.05). At the region of the canines, the clearance value
      for the SLM Co-Cr alloy group was larger than that of the conventional method
      group (P < 0.05). At the mesial of the first molar region and the posterior
      palatal zone, there was no statistical difference between the gaps observed in
      the two groups (P > 0.05). The SLM Co-Cr alloy has a denser microstructure
      behaviour and less casting defect than the cast Co-Cr alloy. The SLM technique
      showed initial feasibility for the manufacture of dental bases of complete
      dentures, but large sample studies are needed to prove its reliability in
      clinical applications. The mechanical properties and microstructure of the
      denture frameworks prepared by selective laser melting indicate that these
      dentures are appropriate for clinical use.

PMID- 29368072
TI  - Culture-based study on the development of antibiotic resistance in a biological
      wastewater system treating stepwise increasing doses of streptomycin.
AB  - The effects of streptomycin (STM) on the development of antibiotic resistance in
      an aerobic-biofilm reactor was explored by stepwise increases in STM doses (0-50
      mg L-1), over a period of 618 days. Totally 191 bacterial isolates affiliated
      with 90 different species were harvested from the reactor exposed to six STM
      exposures. Gammaproteobacteria (20-31.8%), Bacilli (20-35.7%), Betaproteobacteria
      (4.5-21%) and Actinobacteria (0-18.2%) were dominant, and their diversity was not
      affected over the whole period. Thirteen dominant isolates from each STM
      exposures (78 isolates) were applied to determine their resistance prevalence
      against eight classes of antibiotics. Increased STM resistance (53.8-69.2%) and
      multi-drug resistance (MDR) (46.2-61.5%) were observed in the STM exposures (0.1
      50 mg L-1), compared to exposure without STM (15.3 and 0%, respectively). Based
      on their variable minimum inhibitory concentration results, 40 differentiated
      isolates from various STM exposures were selected to check the prevalence of nine
      aminoglycoside resistance genes (aac(3)-II, aacA4, aadA, aadB, aadE, aphA1,
      aphA2, strA and strB) and two class I integron genes (3'-CS and IntI). STM
      resistance genes (aadA, strA and strB), a non-STM resistance gene (aacA4) and
      integron genes (3'-CS and Int1) were distributed widely in all STM exposures,
      compared to the exposure without STM. This new culture-based stepwise increasing
      antibiotic approach reveals that biological systems treating wastewater with
      lower STM dose (0.1 mg L-1) could lead to notably increased levels of STM
      resistance, MDR, and resistant gene determinants, which were sustainable even
      under higher STM doses (> 25 mg L-1).

PMID- 29368073
TI  - "Aspirations of people who come from state education are different": how language
      reflects social exclusion in medical education.
AB  - Despite repeated calls for change, the problem of widening access (WA) to
      medicine persists globally. One factor which may be operating to maintain social
      exclusion is the language used in representing WA applicants and students by the
      gatekeepers and representatives of medical schools, Admissions Deans. We
      therefore examined the institutional discourse of UK Medical Admissions Deans in
      order to determine how values regarding WA are communicated and presented in this
      context. We conducted a linguistic analysis of qualitative interviews with
      Admissions Deans and/or Staff from 24 of 32 UK medical schools. Corpus
      Linguistics data analysis determined broad patterns of frequency and word lists.
      This informed a critical discourse analysis of the data using an "othering" lens
      to explore and understand the judgements made of WA students by Admissions Deans,
      and the practices to which these judgments give rise. Representations of WA
      students highlighted existing divides and preconceptions in relation to WA
      programmes and students. Through using discourse that can be considered othering
      and divisive, issues of social divide and lack of integration in medicine were
      highlighted. Language served to reinforce pre-existing stereotypes and a
      significant 'us' and 'them' rhetoric exists in medical education. Even with
      drivers to achieve diversity and equality in medical education, existing social
      structures and preconceptions still influence the representations of applicants
      and students from outside the 'traditional' medical education model in the UK.
      Acknowledging this is a crucial step for medical schools wishing to address
      barriers to the perceived challenges to diversity.

PMID- 29368075
TI  - A legacy of words.

PMID- 29368074
TI  - Association between duration of intravenous antibiotic administration and early
      life microbiota development in late-preterm infants.
AB  - Antibiotic treatment is common practice in the neonatal ward for the prevention
      and treatment of sepsis, which is one of the leading causes of mortality and
      morbidity in preterm infants. Although the effect of antibiotic treatment on
      microbiota development is well recognised, little attention has been paid to
      treatment duration. We studied the effect of short and long intravenous
      antibiotic administration on intestinal microbiota development in preterm
      infants. Faecal samples from 15 preterm infants (35 +/- 1 weeks gestation and
      2871 +/- 260 g birth weight) exposed to no, short (<= 3 days) or long (>= 5 days)
      treatment with amoxicillin/ceftazidime were collected during the first six
      postnatal weeks. Microbiota composition was determined through 16S rRNA gene
      sequencing and by quantitative polymerase chain reaction (qPCR). Short and long
      antibiotic treat ment significantly lowered the abundance of Bifidobacterium
      right after treatment (p = 0.027) till postnatal week three (p = 0.028). Long
      treatment caused Bifidobacterium abundance to remain decreased till postnatal
      week six (p = 0.009). Antibiotic treatment was effective against members of the
      Enterobacteriaceae family, but allowed Enterococcus to thrive and remain dominant
      for up to two weeks after antibiotic treatment discontinuation. Community
      richness and diversity were not affected by antibiotic treatment, but were
      positively associated with postnatal age (p < 0.023) and with abundance of
      Bifidobacterium (p = 0.003). Intravenous antibiotic administration during the
      first postnatal week greatly affects the infant's gastrointestinal microbiota.
      However, quick antibiotic treatment cessation allows for its recovery.
      Disturbances in microbiota development caused by short and, more extensively, by
      long antibiotic treatment could affect healthy development of the infant via
      interference with maturation of the immune system and gastrointestinal tract.

PMID- 29368076
TI  - The socioeconomic impact of a pediatric ostomy in Uganda: a pilot study.
AB  - INTRODUCTION: Multiple pediatric surgical conditions require ostomies in low
      middle-income countries. Delayed presentations increase the numbers of ostomies.
      Patients may live with an ostomy for a prolonged time due to the high backlog of
      cases with insufficient surgical capacity. In caring for these patients in
      Uganda, we frequently witnessed substantial socioeconomic impact of their
      surgical conditions. METHODS: The operative log at the only pediatric surgery
      referral center in Uganda was reviewed to assess the numbers of children
      receiving ostomies over a 3-year period. Charts for patients with anorectal
      malformations (ARM) and Hirschsprung's disease (HD) were reviewed to assess
      delays in accessing care. Focus group discussions (FGD) were held with family
      members of children with ostomies based on themes from discussions with the
      surgical and nursing teams. A pilot survey was developed based on these themes
      and administered to a sample of patients in the outpatient clinic. RESULTS:
      During the period of January 2012-December 2014, there was one specialty
      certified pediatric surgeon in the country. There were 493 ostomies placed for
      ARM (n = 234), HD (N = 114), gangrenous ileocolic intussusception (n = 95) and
      typhoid-induced intestinal perforation (n = 50). Primary themes covered in the
      FGD were: stoma care, impact on caregiver income, community integration of the
      child, impact on family unit, and resources to assist families. Many patients
      with HD and ARM did not present for colostomy until after 1 year of life. None
      had access to formal ostomy bags. 15 caregivers completed the survey. 13 (86%)
      were mothers and 2 (13%) were fathers. Almost half of the caregivers (n = 7, 47%)
      stated that their spouse had left the family. 14 (93%) caregivers had to leave
      jobs to care for the stoma. 14 respondents (93%) reported that receiving advice
      from other caregivers was beneficial. CONCLUSION: The burden of pediatric
      surgical disease in sub-Saharan Africa is substantial with significant
      disparities compared to high-income countries. Significant socioeconomic
      complexity surrounds these conditions. While some solutions are being
      implemented, we are seeking resources to implement others. This data will inform
      the design of a more expansive survey of this patient population to better
      measure the socioeconomic impact of pediatric ostomies and guide more
      comprehensive advocacy and program development.

PMID- 29368077
TI  - Retrospective analysis to determine outcomes of patients with bilateral Wilms
      tumor undergoing nephron sparing surgery: 15-year tertiary single-institution
      experience.
AB  - PURPOSE: To describe our clinical experience with nephron sparing surgery (NSS)
      for bilateral Wilms tumor and evaluate the outcomes of patients treated at one of
      the largest pediatric medical centers in China. METHODS: Medical records of
      children with bilateral Wilms tumor undergoing NSS in the Children's Hospital of
      Chongqing Medical University during a 15-year period were retrospectively
      analyzed. Data collected were composed of age at surgery, tumor response, tumor
      rupture during resection, final pathologic margins, use of radiation therapy,
      pathology reports, renal function, and patient survival. RESULTS: A total of 18
      eligible patients (10 males, 8 females) with bilateral Wilms tumor at a mean age
      of 2.28 +/- 1.12 years were identified. The administration of preoperative
      chemotherapy did not result in universally successful outcomes. All children
      underwent successfully unilateral or bilateral NSS, of which one had positive
      pathologic margins and five received radiation therapy postoperatively. The rates
      of tumor rupture and positive lymph nodes involvement were 11.1 and 19.4%,
      respectively. The pathological study showed favorable histology and unfavorable
      histology in 32 and 4 kidneys, respectively. The 4-year event-free survival and
      overall survival rates were 68.18 and 85.56%. In univariable analysis, tumor
      histology (p = 0.0028) and disease stage (p = 0.0303) appeared significantly
      associated with overall survival. After a median follow-up period of 41.5 months
      (range 10-89), three of the surviving patients were diagnosed with hypertension
      and one had renal insufficiency. CONCLUSIONS: Our experience suggests that NSS
      has become a feasible and effective option with good oncologic outcomes. Further
      research, ideally in a multicenter randomized manner, is warranted to better
      assess the role of NSS in this challenging clinical scenario.

PMID- 29368078
TI  - Kasai procedure improves nutritional status and decreases transplantation
      associated complications.
AB  - BACKGROUND: The aim of this study was to retrospectively investigate whether
      Kasai Procedure (KP) improves nutritional status and whether KP decreases liver
      transplantation (LT)-associated complications in children with biliary atresia
      (BA). METHODS: From March 1st 2014 to February 28th 2015, 103 patients underwent
      LT and the other 17 without prior KP died during the waiting period. In 103
      patients undergoing LT, 58 patients received KP previously (Group A), and 45 only
      underwent primary LT (Group B). The nutritional status, liver function and LT
      related short-term complications were analyzed. RESULTS: Compared to Group B,
      patients in Group A had significantly increased time interval when undergoing LT
      (p < 0.05). Persistently, the bodyweight, albumin and hemoglobin in Group A were
      significantly increased compared to Group B (all, p < 0.0001). The bilirubin,
      ALT/AST and PELD score in Group A were all decreased compared to Group B (p <
      0.05) prior to LT. The incidences of post-LT severe infection and hypoalbuminemia
      in Group A were significantly lower than those of Group B (p < 0.05).
      CONCLUSIONS: KP improves the nutritional status, preserves liver function for
      patients who finally undergo LT, and decreases the incidence post-LT severe
      infection and hypoalbuminemia. Mental health can be improved in parents whose
      children underwent previous KP.

PMID- 29368079
TI  - Modeling the Effect of Prey Refuge on a Ratio-Dependent Predator-Prey System with
      the Allee Effect.
AB  - The extinction of species is a major threat to the biodiversity. The species
      exhibiting a strong Allee effect are vulnerable to extinction due to predation.
      The refuge used by species having a strong Allee effect may affect their
      predation and hence extinction risk. A mathematical study of such behavioral
      phenomenon may aid in management of many endangered species. However, a little
      attention has been paid in this direction. In this paper, we have studied the
      impact of a constant prey refuge on the dynamics of a ratio-dependent predator
      prey system with strong Allee effect in prey growth. The stability analysis of
      the model has been carried out, and a comprehensive bifurcation analysis is
      presented. It is found that if prey refuge is less than the Allee threshold, the
      incorporation of prey refuge increases the threshold values of the predation rate
      and conversion efficiency at which unconditional extinction occurs. Moreover, if
      the prey refuge is greater than the Allee threshold, situation of unconditional
      extinction may not occur. It is found that at a critical value of prey refuge,
      which is greater than the Allee threshold but less than the carrying capacity of
      prey population, system undergoes cusp bifurcation and the rich spectrum of
      dynamics exhibited by the system disappears if the prey refuge is increased
      further.

PMID- 29368080
TI  - The Ebbinghaus illusion with small inducers appears larger on the right side.
AB  - The effects of left and right alignment on the Ebbinghaus illusion were
      investigated in three experiments. In Experiment 1, the Ebbinghaus illusion was
      presented on the left or right side, and the points of subjective equality (PSE)
      were measured. Only the central disk of the figure with small inducers was
      perceived larger when it was positioned on the right side rather than on the
      left. In Experiments 2 and 3, left, right, and central placement were used to
      determine if the results of Experiment 1 were caused by a decrease of the
      illusion on the left side or an increase of the illusion on the right side. There
      was no difference in the illusion effect between the left and the center;
      however, the illusion effect increased when the figure was presented on the right
      side. These results suggest that a hemispheric asymmetry for global and local
      spatial attention influences the laterality of the Ebbinghaus illusion.

PMID- 29368081
TI  - [Influence of centralization on the outcome of esophageal perforation].

PMID- 29368082
TI  - Chondroid nodule in the female peritoneum arises from normal tissue and not from
      teratoma or conception product.
AB  - The pathogenesis of benign-looking cartilaginous tissue within the peritoneum is
      unknown. Chondroid metaplasia of subcoelomic mesenchyme has been suggested, as
      has been the case for other gynecological diseases such as endometriosis,
      peritoneal leiomyomatosis, or gliomatosis peritonei, but has never been proven.
      Chondroid nodules in the peritoneum may represent either teratomatous tissue,
      fetal rests from a conception product, or metaplasia of pluripotent mesenchymal
      cells. Herein, the unique genetic characteristics of ovarian teratomas
      (homozygous at many polymorphic microsatellite loci) versus normal tissues
      (heterozygous at the same loci) were used to investigate the origin of chondroid
      nodules in the peritoneum. DNA samples extracted from paraffin-embedded normal
      peritoneal tissue and chondroid peritoneal nodules from two patients were
      studied. In both cases, chondroid and normal tissue showed heterozygosity at each
      informative microsatellite locus on different chromosomes, with a profile similar
      to the mother. These results indicate that peritoneal chondroid nodules arise
      within the peritoneum, presumably from pluripotent mesodermal stem cells, and are
      not related to teratomatous proliferation, or previous pregnancy. This finding
      shows once again the plasticity and metaplastic potential of stem cells within
      the peritoneal cavity.

PMID- 29368084
TI  - Radiological classification of retroperitoneal hematoma resulting from lumbar
      vertebral fracture.
AB  - PURPOSE: Lumbar vertebral fracture (LVF) infrequently produces massive
      retroperitoneal hematoma (RPH). This study aimed to systematically review the
      clinical and radiographic characteristics of RPH resulting from LVF. METHODS: For
      193 consecutive patients having LVF who underwent computed tomography (CT),
      demographic data, physiological conditions, and outcomes were reviewed from their
      medical records. Presence or absence of RPH, other bone fractures, or
      organ/vessel injury was evaluated in their CT images, and LVF or RPH, if present,
      was classified according to either the Orthopaedic Trauma Association
      classification or the concept of interfascial planes. RESULTS: RPH resulting only
      or dominantly from LVF was found in 66 (34.2%) patients, whereas among the
      others, 64 (33.2%) had no RPH, 38 (19.7%) had RPH from other injuries, and 25
      (13.0%) had RPH partly attributable to LVF. The 66 RPHs resulting only or
      dominantly from LVF were radiologically classified into mild subtype of minor
      median (n = 35), moderate subtype of lateral (n = 11), and severe subtypes of
      central pushing-up (n = 13) and combined (n = 7). Of the 20 patients with severe
      subtypes, 18 (90.0%) were in hemorrhagic shock on admission, and 6 (30.0%) were
      clinically diagnosed as dying due to uncontrollable RPH resulting from vertebral
      body fractures despite no anticoagulant medication. CONCLUSIONS: LVF can directly
      produce massive RPH leading to hemorrhagic death. A major survey of such
      pathology should be conducted to establish appropriate diagnosis and treatment.

PMID- 29368083
TI  - Reduced immunohistochemical PTEN staining is associated with higher progression
      rate and recurrence episodes in non-invasive low-grade papillary urothelial
      carcinoma of the bladder.
AB  - Non-invasive low-grade papillary urothelial carcinoma (NILGPUC) of the bladder is
      regarded as a relatively indolent disease. However, its propensity for frequent
      recurrences constitutes a major clinical problem. Additionally, there is a
      progression risk of 10-15% to either a higher grade and/or a higher stage disease
      in these tumors. The molecular factors that will predict recurrence and
      progression in low-grade pTa bladder carcinoma have not yet been elucidated.
      Herein, we investigated the association of phosphatase and tensin homolog deleted
      on chromosome 10 (PTEN) alterations with recurrence and progression in NILGPUC
      using immunohistochemistry. Eighty-one cases of bladder cancer initially
      diagnosed as NILGPUC in a single institution with follow-up were encountered
      after searching medical records. Tissue microarrays (TMA) that contained both
      tumor and non-neoplastic mucosa from each case were constructed using paraffin
      blocks of transurethral resections. Sections from TMA blocks were stained
      immunohistochemically for PTEN protein and were evaluable in 76 cases. Any
      absence of staining was recorded and correlated with clinical findings. Ten
      patients (13.2%) showed progression and 41 (53.9%) showed recurrence. Reduced
      PTEN expression was observed in 29 cases (38.1%). Cases with reduced PTEN had
      higher progression rate compared to cases with intact PTEN (p = 0.026). Tumor
      relapse was more frequent in cases with reduced PTEN (65.5 vs 46.8%), but this
      difference was not statistically significant (p = 0.112). On the other hand,
      decreased PTEN expression was associated with higher number of recurrence
      episodes (p = 0.002). PTEN seems to have a link with the disease course in
      NILGPUC of the bladder.

PMID- 29368085
TI  - Selective nonoperative management of liver gunshot injuries.
AB  - PURPOSE: Nonoperative management (NOM) of gunshot liver injuries (GLI) is
      infrequently practiced. The aim of this study was to assess the safety of
      selective NOM of GLI. METHODS: A prospective, protocol-driven study, which
      included patients with GLI admitted to a level 1 trauma center, was conducted
      over a 52-month period. Stable patients without peritonism or sustained
      hypotension with right-sided thoracoabdominal (RTA) and right upper quadrant
      (RUQ), penetrating wounds with or without localized RUQ tenderness, underwent
      contrasted abdominal CT scan to determine the trajectory and organ injury.
      Patients with established liver and/or kidney injuries, without the evidence of
      hollow viscus injury, were observed with serial clinical examinations. Outcome
      parameters included the need for delayed laparotomy, complications, the length of
      hospital stay and survival. RESULTS: During the study period, 54 (28.3%) patients
      of a cohort of 191 patients with GLI were selected for NOM of hemodynamic
      stability, the absence of peritonism and CT imaging. The average Revised Trauma
      Score (RTS) and Injury Severity Score (ISS) were 7.841 and 25 (range 4-50),
      respectively. 21 (39%) patients had simple (Grades I and II) and 33 (61%)
      patients sustained complex (Grades III to V) liver injuries. Accompanying
      injuries included 12 (22.2%) kidney, 43 (79.6%) diaphragm, 20 (37.0%) pulmonary
      contusion, 38 (70.4%) hemothoraces, and 24 (44.4%) rib fractures. Three patients
      required delayed laparotomy resulting in an overall success of NOM of 94.4%.
      Complications included: liver abscess (1), biliary fistula (5), intrahepatic A-V
      fistula (1) and hospital-acquired pneumonia (3). The overall median hospital stay
      was 6 (IQR 4-11) days, with no deaths. CONCLUSION: The NOM of carefully selected
      patients with GLI is safe and associated with minimal morbidity.

PMID- 29368086
TI  - Correction to: Radiopharmaceutical tracers for cardiac imaging.
AB  - Regrettably the original version of the above article contained errors in the
      three chemical structures presented in the 'Atherosclerosis imaging' section of
      Table 5, namely: 99mTc annexin V, 68Ga DOTATATE, and 64Cu DOTATATE; the chemical
      structures have been corrected in Table presented here. In addition, the
      radiopharmaceutical for isotope 67Ga has been corrected to 67Ga citrate, and many
      of the radiopharmaceuticals presented at the end of the table have been
      corrected.

PMID- 29368087
TI  - Author's response to Letter-to-the-editor regarding "Are the Epworth Sleepiness
      Scale and Stop-Bang Model effective at predicting the severity of obstructive
      Sleep Apnoea (OSA); in particular OSA requiring treatment?"

PMID- 29368088
TI  - Reply to the letter concerning "Revision adenoidectomy in children: a population
      based cohort study in Taiwan".

PMID- 29368092
TI  - Unscripted Responsible Research and Innovation: Adaptive space creation by an
      emerging RRI practice concerning juvenile justice interventions.
AB  - Emerging RRI practices have goals with respect to learning, governance and
      achieving RRI outcomes (action). However, few practices actually achieve the
      action phase as actors lack room to manoeuvre, and lack guidance on how to move
      forward because of the inherent unscriptedness of the emerging RRI practice. In
      this explorative research an emerging RRI practice is studied to identify factors
      and barriers to the creation of adaptive space, in which actors can be responsive
      to the other and adapt, and a narrative can be created in the act of doing. This
      paper describes how formal and informal ways of organizing emerging RRI practices
      contribute to adaptive space, and how the metaphorical heuristic of
      improvisational theatre provides clear action principles to actors involved in
      emerging RRI practices in action. The RRI practice studied here lies in the
      domain of juvenile justice, where barriers that restrict room to manoeuvre are
      abundant. Five factors - 'informality over formality', 'shared action space', 'be
      flexible', 'keep the action moving' and 'put the relationship central' - were
      identified to facilitate reflexivity and adaptation in this space.

PMID- 29368091
TI  - Population genetic diversity in zebrafish lines.
AB  - Toxicological and pharmacological researchers have seized upon the many benefits
      of zebrafish, including the short generation time, well-characterized
      development, and early maturation as clear embryos. A major difference from many
      model organisms is that standard husbandry practices in zebrafish are designed to
      maintain population diversity. While this diversity is attractive for
      translational applications in human and ecological health, it raises critical
      questions on how interindividual genetic variation might contribute to chemical
      exposure or disease susceptibility differences. Findings from pooled samples of
      zebrafish support this supposition of diversity yet cannot directly measure
      allele frequencies for reference versus alternate alleles. Using the Tanguay lab
      Tropical 5D zebrafish line (T5D), we performed whole genome sequencing on a large
      group (n = 276) of individual zebrafish embryos. Paired-end reads were collected
      on an Illumina 3000HT, then aligned to the most recent zebrafish reference genome
      (GRCz10). These data were used to compare observed population genetic variation
      across species (humans, mice, zebrafish), then across lines within zebrafish. We
      found more single nucleotide polymorphisms (SNPs) in T5D than have been reported
      in SNP databases for any of the WIK, TU, TL, or AB lines. We theorize that some
      subset of the novel SNPs may be shared with other zebrafish lines but have not
      been identified in other studies due to the limitations of capturing population
      diversity in pooled sequencing strategies. We establish T5D as a model that is
      representative of diversity levels within laboratory zebrafish lines and
      demonstrate that experimental design and analysis can exert major effects when
      characterizing genetic diversity in heterogeneous populations.

PMID- 29368093
TI  - Parkinson's Disease, the Dopaminergic Neuron and Gammahydroxybutyrate.
AB  - The high energy demands of the substantia nigra pars compacta dopaminergic
      (DASNc) neurons render these neurons vulnerable to degeneration. These energy
      demands are a function of their long and extensively arborized axons and very
      large number of transmitter release sites, and are further augmented by their
      natural pacemaking activity. Pacemaking is driven by the rhythmic entry of Ca2+
      into the cell and, while the entry of Ca2+ into the neuron stimulates energy
      (ATP) production, the extrusion of Ca2+ conversely saps the energy that is
      generated. DASNc neurons are said to be operating at a delicate equilibrium where
      any further stress or environmental demand may lead to their decompensation and
      degeneration. In experimental models of Parkinson's disease, reducing the energy
      requirements of these neurons by trimming the size of the neuronal arbor or by
      impeding the entry of Ca2+ into the cell has been shown to be protective.
      Increasing the energy supply to these neurons with D-beta-hydroxybutyrate has
      also been shown to be protective. The use of gammahydroxybutyrate holds great
      promise as a neuroprotective in Parkinson's disease because it can act as an
      energy source for the cell while simultaneously arresting its pacemaking activity
      and the entry of Ca2+ into the cell. Short clinical trials of
      gammahydroxybutyrate in Parkinson's disease have already demonstrated its
      immediate capacity to significantly reduce daytime fatigue and sleepiness and to
      improve sleep at night.

PMID- 29368094
TI  - Correction to: Tryptophan depletion under conditions that imitate insulin
      resistance enhances fatty acid oxidation and induces endothelial dysfunction
      through reactive oxygen species-dependent and independent pathways.
AB  - In the original publication of the article, last author's name was misspelt. The
      correct name is given here.

PMID- 29368095
TI  - Falcarindiol inhibits LPS-induced inflammation via attenuating MAPK and JAK-STAT
      signaling pathways in murine macrophage RAW 264.7 cells.
AB  - Falcarindiol (FAD) is a natural polyacetylene compound found rich in many plants
      of the Umbelliferae family. Previously, we isolated FAD from the rhizome of
      Cnidium officinale Makino, which belongs to the Umbelliferae family and found it
      to have a significant inhibitory effect on lipopolysaccharide (LPS)-induced
      production of nitric oxide, a pro-inflammatory molecule in murine macrophage RAW
      264.7 cells. In this study, we investigated its effect on the expression of other
      major pro-inflammatory molecules as well as the mechanism underlying these
      effects. Pre-treatment of RAW 264.7 cells with FAD suppressed LPS-stimulated mRNA
      expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha
      (TNFalpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1beta) and thereby
      reduced the respective protein levels. Mechanistic studies demonstrated that FAD
      attenuated the LPS-induced activation of JNK, ERK, STAT1, and STAT3 signaling
      molecules. Moreover, we found that FAD did not influence LPS-induced activation
      of p38 and NFkappaB signaling pathways. Collectively, this study provides
      evidence that FAD inhibits the production of major pro-inflammatory molecules in
      LPS-challenged murine macrophages via suppression of JNK, ERK, and STAT signaling
      pathways.

PMID- 29368097
TI  - Sudden development of adult-onset type II citrullinemia after total gastrectomy:
      a case report.
AB  - BACKGROUND: Adult-onset type II citurullinemia is an autosomal recessive disorder
      characterized by recurrent encephalopathy with hyperammonemia resulting from high
      plasma citrulline and ammonium levels. This report describes a rare case of adult
      onset type II citurullinemia that occurred in a patient who only had the
      heterozygote mutation, and had never presented with any symptoms before surgery.
      CASE PRESENTATION: A 56-year-old man underwent a total gastrectomy for stomach
      cancer. On postoperative Day 13, he suddenly developed presyncope, and blood
      tests showed hyperammonemia and high levels of serum citrulline. He was diagnosed
      with hepatic encephalopathy. DNA analysis revealed a heterozygote mutation in
      Solute Carrier Family 25. Although the patient received a conservative treatment,
      episodes of loss of consciousness and abnormality of behavior repeatedly
      occurred. CONCLUSION: Abdominal surgery involving the reconstruction of digestive
      tract alters the mechanisms of absorption and/or metabolism such that the
      symptoms of adult-onset type II citurullinemia may arise. Liver transplantation
      should be performed if all conservative treatments are unsuccessful.

PMID- 29368098
TI  - Submandibular lymphadenopathy in a child post-renal transplant-"What lies
      beneath?!": Questions.

PMID- 29368096
TI  - Decitabine augments cytotoxicity of cisplatin and doxorubicin to bladder cancer
      cells by activating hippo pathway through RASSF1A.
AB  - Genetic abnormalities and epigenetic alterations both play vital role in
      initiation as well as progression of cancer. Whereas genetic mutations cannot be
      reversed, epigenetic alterations such as DNA methylation can be reversed by the
      application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing
      of RASSF1A and involvement of hippo pathway both have been shown to involve in
      chemo-resistance. Purpose of this study was to observe the effect of combination
      treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells
      involving hippo pathway through RASSF1A. Bladder cancer cells (HT1376 & T24) were
      treated with decitabine and its effect on RASSF1A expression, hippo pathway
      molecules (MST & YAP), and its downstream targets (CTGF, CYR61 & CTGF) was
      observed. Effect of decitabine pretreatment on sensitivity of bladder cancer
      cells towards chemotherapeutic drugs was also studied. Decitabine treatment leads
      to restoration of RASSF1A, activation of hippo pathway followed by decreased
      expression of its oncogenic downstream targets (CTGF & CYR61). Further
      pretreatment of decitabine enhanced cytotoxicity of cisplatin and doxorubicin to
      bladder cancer cells.

PMID- 29368099
TI  - Submandibular lymphadenopathy in a child post-renal transplant-"What lies
      beneath?!": Answers.

PMID- 29368100
TI  - Erratum to: Fungal and plant gene expression in arbuscular mycorrhizal symbiosis.

PMID- 29368101
TI  - Erratum to: Mycorrhiza for science and society-5th International Conference on
      Mycorrhiza (ICOM5).

PMID- 29368103
TI  - Culturally-Relevant Online Education Improves Health Workers' Capacity and Intent
      to Address Cancer.
AB  - To address a desire for timely, medically-accurate cancer education in rural
      Alaska, ten culturally-relevant online learning modules were developed,
      implemented, and evaluated with, and for, Alaska's Community Health
      Aides/Practitioners (CHA/Ps). The project was guided by the framework of
      Community-Based Participatory Action Research, honored Indigenous Ways of
      Knowing, and was informed by Empowerment Theory. Each learner was invited to
      complete an end-of-module evaluation survey. The survey asked about changes in
      intent to share cancer information with patients as a result of the module. In 1
      year, August 1, 2016-July 31, 2017, 459 surveys were completed by 79 CHA/Ps.
      CHA/Ps reported that, because of the modules, they felt more knowledgeable about
      cancer, and more comfortable, confident, and prepared to talk about cancer with
      their patients, families, and communities. All learners shared that because of
      the modules, they intended to talk with their patients more often about cancer
      screenings, tobacco cessation, physical activity, or nutrition. These findings
      suggest that the application of this collaboratively developed, culturally
      relevant, health promotion intervention has supported increased CHA/P capacity
      and intent to interact with patients about cancer. In the words of a learner:
      "Doing all these courses makes me a ton times more comfortable in talking about
      cancer with anyone. I didn't know too much about it at first but now I know a
      whole lot. Thank you".

PMID- 29368102
TI  - Human Papilloma Virus Vaccination Among Adolescents in a Community Clinic Before
      and After Intervention.
AB  - Human Papilloma Virus (HPV) is the most common sexually transmitted disease with
      over 14 million infections in 2008. Certain HPV types have been identified in up
      to 70% of cases of cervical and anal cancers. Despite being safe and effective,
      HPV vaccination rates remain low. Vaccination and demographic data was collected
      pre-and post-intervention. Among 13 thru 17-year-old cohort females were
      significantly more likely to be fully vaccinated. Assessment also found that
      patients insured by Medicaid were significantly more likely to be fully
      vaccinated than patients insured privately. Post-intervention vaccination rate is
      similar to baseline rates. There was non-significant improvement in HPV
      vaccination coverage after intervention. Male and privately insured patients of
      Creighton's Pediatric Clinic have lower HPV vaccination coverage than their
      counterparts. More direct efforts are needed in vaccination process and policy in
      the clinic to improve immunization against HPV among children and adolescents.

PMID- 29368104
TI  - Discrimination and Health Among Taxi Drivers in New York and Toronto.
AB  - Immigrant taxi drivers in metropolitan cities are exposed to experiences of
      discrimination and occupation-based health risks. Given the structural
      differences in health care systems in the United States and Canada, we
      investigated the differences in reports of discrimination, health conditions and
      concern about health conditions between taxi drivers in New York City and
      Toronto, Ontario. Participants were recruited for a taxi driver Needs Assessment
      Survey as part of a Taxi Network needs assessment project using a street side
      convenience sampling technique in New York City and Toronto. The matched sample
      contained 33 drivers from Toronto and 33 drivers from NYC. All Toronto drivers in
      our sample reported having health insurance while over a quarter of NYC drivers
      did not have health insurance. Toronto drivers reported greater everyday and
      workplace discrimination. Drivers in both cities experienced higher rates than
      average, and reported concern about, major health conditions. We also found
      preliminary evidence suggesting a relationship between experiencing
      discrimination and reporting chronic pain. Our findings suggest the need for
      future research to more closely examine the associations between discrimination
      and health among the taxi driver population.

PMID- 29368105
TI  - Rapid Transition of Facial Features from Early to Mid - Adolescence in Autosomal
      Dominant Hyper IgE Syndrome with a STAT3 Variation.

PMID- 29368106
TI  - Field Testing of IAP2015 Charts.
AB  - OBJECTIVES: To field test the IAP2015 (Indian Academy of Pediatrics) charts in
      different socioeconomic classes; to compare standard deviation scores (Z-scores)
      of children's height, weight and body mass index (BMI) for age as computed based
      on IAP2007 or WHO charts against the IAP2015 references. METHODS: A cross
      sectional observational study was conducted in the district of Pune on apparently
      healthy 5-18 y old children from urban affluent, urban underprivileged and rural
      areas. Anthropometric measurements were performed and parameters were converted
      into Z-scores. RESULTS: Urban affluent children were tallest and heaviest whereas
      urban underprivileged children were shortest. Z-score comparison showed that all
      children were shortest on WHO references and taller as per IAP2007 references.
      BMI Z-score was higher on IAP2007 charts and lower on WHO references. Highest
      number of children were within the reference range on IAP2015 charts among urban
      affluent. More children were classified stunted on WHO references and least on
      IAP2007 references. WHO references overestimated wasting and as per IAP2007
      charts, less number were wasted. Less number of children were classified as being
      obese/overweight by WHO and IAP2007 references. CONCLUSIONS: IAP2015 charts are
      better representative of healthy children of current generation and may be used
      to prevent inappropriate classification in present scenario.

PMID- 29368107
TI  - Predictors of Severity in Pediatric Scrub Typhus.
AB  - OBJECTIVE: To identify the factors that can predict the severity of scrub typhus
      in children. METHODS: This prospective study was conducted at a tertiary care
      teaching hospital between November 2014 to October 2016. All children <12y of age
      admitted with fever for more than 7d and positive IgM ELISA for scrub typhus were
      included in the study. These children were followed during the hospital course
      and their laboratory results, response to treatment and complications were
      documented. Cases of 'severe scrub typhus' were identified based on criteria from
      published adult and pediatric studies. RESULTS: Out of 930 children with fever
      for more than 7d, IgM ELISA for scrub typhus was positive in 230 children. Ninety
      one (40.6%) cases fulfilled the criteria of 'severe scrub typhus' in children.
      Out of 45 factors, 27 potential factors were studied. The multivariate analysis
      identified 5 factors, breathlessness (OR: 6.85, 95%CI: 2.69 to 9.87), altered
      sensorium (OR: 11.48, 95% CI 3.43 to 10.19), leucocytosis (OR: 3.38, 95% CI 1.12
      to 10.16), hypoalbuminemia (OR: 10.78, 95% CI 2.66 to 48.76), and hyponatremia
      (OR: 10.08, 95% CI 2.11 to 23.42) to be significantly associated with the 'severe
      scrub typhus' cases. CONCLUSIONS: Breathlessness, altered sensorium,
      leucocytosis, hypoalbuminemia, and hyponatremia predict severity in childhood
      scrub typhus. Presence of these factors should alert the treating physician
      regarding the need for intensive monitoring, treatment or referral.

PMID- 29368108
TI  - Intracranial Hematopoiesis in Beta Thalassemia: A Case Series.
AB  - Extramedullary hematopoiesis (EMH) is a normal response to failure of
      hematopoiesis at its normal site i.e., bone marrow. It is a manifestation of many
      congenital hemolytic anemias and marrow failure secondary to myelodysplastic
      syndromes. Usually, extramedullary myeloid proliferation occurs in liver, spleen
      and lymph nodes. However, there are many unusual sites where EMH can occur. The
      authors report two cases of intracranial extramedullary hematopoiesis in beta
      thalassemia. In one of these patients, epidural soft tissue was detected along
      frontal and parietal convexities causing compression of brain parenchyma leading
      to raised intracranial tension and sagging of brain stem, corpus callosum and
      herniation of cerebellar tonsils. The other case had a similar but unilateral
      epidural soft tissue. Expansion of diploic spaces of skull was seen in both these
      cases. As myeloid proliferation is slow, it presents with subtle symptoms of
      headache and gradually progressive lower limb weakness. A high index of clinical
      suspicion coupled with imaging findings is the only way to confirm the diagnosis.

PMID- 29368109
TI  - 'Quality of Life' of Parents of Children Suffering from Pediatric Malignancies in
      a Low Income Setting.
AB  - OBJECTIVES: To evaluate the impact of pediatric malignancies on quality of life
      (QOL) and psychological status of parents and to correlate it with well-matched
      controls and socioeconomic status. METHODS: A prospective comparative cross
      sectional study was conducted. Seventy parents of children diagnosed with
      pediatric malignancies within the last three months were enrolled in the study
      group (SG) and 50 matched parents of healthy children as the control group (CG).
      Assessment was done by WHOQOL-BREF questionnaire, Depression Anxiety Stress Score
      (DASS) scale and Kuppuswamy scale. Data analysis was done by using Statistical
      Package for social sciences (SPSS) version 20.0. p value <0.05 considered as
      significant. RESULTS: Mean score of QOL for SG in physical health domain (D1),
      psychological health (D2), social relationships (D3) and environment health (D4)
      was 48.64, 43.07, 47.36, and 40.58 respectively whereas that of CG was 79.38,
      76.32, 80.58 and 72.86 respectively and the difference was statistically
      significant (p value <0.001). The environmental domain (D4) had the lowest mean
      score amongst all domains in the SG. QOL was maximally affected by the parameter
      sleep, depression, personal relationship and lack of information in the
      respective domains. Mean depression, anxiety and stress score of SG was 23.43,
      20.33, 23.56 respectively whereas that of the CG was 7.1, 8.06 and 8.54
      respectively and this was statistically significant (p value <0.001). The QOL of
      SG in D1 for the lower socioeconomic class was 48.86 and for the upper class was
      63 and this difference was statistically significant (p value <0.015). Similarly
      in D2 and D4 the QOL scores went higher with the socioeconomic class and this was
      statistically significant (p value < 0.007 and p value <0.030 respectively).
      CONCLUSIONS: SG had poorer QOL and were significantly more depressed, anxious and
      stressed. It is concluded that effective interventions are needed to aid these
      families to improve outcomes by delivering the benefit of vastly improved
      therapeutic strategies in this field.

PMID- 29368110
TI  - Effect of Folic Acid Supplementation on Seizure Control in Epileptic Children
      Receiving Long Term Antiepileptic Therapy.
AB  - OBJECTIVE: To evaluate the effect of folic acid supplementation on seizure
      control in folate deficient children receiving long term antiepileptic therapy.
      METHODS: In a prospective interventional study, 140 children between age group 6
      mo to 180 mo fulfilling the inclusion criteria were enrolled in study group, from
      October 2015 through November 2016. On the basis of serum folate, study group was
      divided into two subgroups by non randomization: Group A (<10 ng/ml) given folic
      acid supplementation for 3 mo and Group B (>10 ng/ml) was not supplemented.
      Response to folic acid supplementation in group A was compared with group B in
      terms of change in blood folate levels, frequency and duration of seizures after
      three months. RESULTS: Mean age of study group was 73.58 +/- 46.89 mo (72.14%
      boys and 27.85% girls). 67.85% children were in group A and 32.14% in group B. On
      3 mo follow up, children supplemented with folic acid (Group A) had significant
      fall in mean seizure frequency while in non-supplemented children (Group B), no
      significant change was seen (p value <0.05). Similar reduction in duration of
      seizure episode was seen in group A as compared to group B. Serum and RBC folate
      levels improved from baseline in group A, while in group B there was significant
      fall in folate levels. CONCLUSIONS: Folate deficiency is common in epileptic
      children on long term antiepileptic drugs (AEDs), contributes to poor seizure
      control and should be considered in the etiologic differentials of drug resistant
      epilepsy. Folate supplementation improves seizure control in these children.

PMID- 29368111
TI  - Effects of Taurine Supplementation on Growth in Low Birth Weight Infants: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To summarize the available randomized controlled trials (RCTs) to
      evaluate the effect of taurine supplementation on growth in low birth weight
      infants (LBW). METHODS: PubMed, EmBase, and Cochrane Library electronic databases
      were searched for published articles through March 2017. Analysis was done to
      examine the effect of taurine supplementation on growth, and sensitivity analysis
      was performed by removing each individual study from meta-analysis. RESULTS:
      Results of 9 trials totaling 216 LBW infants in the present meta-analysis were
      collected and analyzed. The conclusion of included studies demonstrated that
      taurine supplementation significantly reduced length gain (WMD:-0.18; P < 0.001),
      plasma glycine (WMD:-106.71; P = 0.033), alanine (WMD:-229.30; P = 0.002),
      leucine (WMD:-64.76; P < 0.001), tyrosine (WMD:-118.11; P < 0.001), histidine
      (WMD:-52.16; P < 0.001), proline (WMD: -84.29; P = 0.033), and asparagine
      glutamine (WMD:-356.30; P < 0.001). However, taurine supplementation was
      associated with higher levels of acidic sterols (WMD:0.61; P = 0.024), total
      fatty acids (WMD:7.94; P = 0.050), total saturated fatty acids (WMD:9.70; P <
      0.001), and unsaturated fatty acids (WMD:6.63; P < 0.001). Finally, taurine
      supplementation had little or no significant effect on weight gain, head
      circumference gain, plasma taurine, threonine, serine, citrulline, valine,
      methionine, isoleucine, phenylalanine, ornithine, lysine, arginine, glutamate,
      hydroxyproline, aspartate, dietary cholesterol, endogenous neutral sterols,
      cholesterol synthesis, and medium-chain triglycerides. CONCLUSIONS: The findings
      suggest that although there are several significant differences in plasma
      indeces, no significant effect on growth in LBW infants was observed with taurine
      supplementation.

PMID- 29368112
TI  - Evolving Treatment Paradigms in Non-clear Cell Kidney Cancer.
AB  - OPINION STATEMENT: With no therapy specifically approved for non-clear cell
      cancers of the kidney, this disease remains an orphan site. Clear cell renal
      cancers (ccRCC) have seen a flurry of activity with multiple agents gaining Food
      and Drug Administration (FDA) approval in recent years. Simultaneously, non-clear
      cell RCC (ncRCC) have also seen a fair share of activity and exploration of new
      agents in development but no specific FDA approvals. Non-clear cell RCC is a
      mixed bag of multiple types of tumors originating in the kidney with distinct
      clinical molecular and genetic characteristics that vary significantly from clear
      cell carcinoma of the kidney. Conventionally, non-clear cell RCC have been
      treated with the same therapies as clear cell RCC. The clinical trials are
      typically conducted in ccRCC and the FDA approval covers non-clear cell cancer as
      well. Few randomized clinical trials have been conducted specifically for ncRCC.
      With the advent of molecular and tumor genomic testing, leading to discovery of
      targets and associated therapies for ncRCC, a specific review of the state of
      management of this disease is timely and clinically relevant.

PMID- 29368113
TI  - 3D Printed "Starmix" Drug Loaded Dosage Forms for Paediatric Applications.
AB  - PURPOSE: Three- dimensional (3D) printing has received significant attention as a
      manufacturing process for pharmaceutical dosage forms. In this study, we used
      Fusion Deposition Modelling (FDM) in order to print "candy - like" formulations
      by imitating Starmix(r) sweets to prepare paediatric medicines with enhanced
      palatability. METHODS: Hot melt extrusion processing (HME) was coupled with FDM
      to prepare extruded filaments of indomethacin (IND), hypromellose acetate
      succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently
      feed them in the 3D printer. The shapes of the Starmix(r) objects were printed in
      the form of a heart, ring, bottle, ring, bear and lion. Differential scanning
      calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red
      Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug -
      excipient interactions and the content uniformity. RESULTS: Physicochemical
      analysis showed the presence of molecularly dispersed IND in the printed tablets.
      In vivo taste masking evaluation demonstrated excellent masking of the drug
      bitterness. The printed forms were evaluated for drug dissolution and showed
      immediate IND release independently of the printed shape, within 60 min.
      CONCLUSIONS: 3D printing was used successfully to process drug loaded filaments
      for the development of paediatric printed tablets in the form of Starmix(r)
      designs.

PMID- 29368114
TI  - Correction to: Synthetic Biology and the Translational Imperative.
AB  - The author group of above-mentioned review paper was incorrectly published in the
      online article.

PMID- 29368115
TI  - Efficacy of low glycemic index treatment in epileptic patients: a systematic
      review.
AB  - Low glycemic index treatment (LGIT) is one of the new kinds of ketogenic diet
      (KD), designed to simplify the implementation of the KD. To date, several studies
      have attempted to determine the efficacy of LGIT in patients with epilepsy;
      however, their results are debatable. This study aims to retrieve all the LGIT
      studies to shed light on LGIT efficacy in epileptic patients. Electronic
      literature databases including MEDLINE/PubMed, Web of Science, Scopus, EMBASE
      were searched in July 2017. Interventional or observational studies exploring the
      efficacy of LGIT were included in the study. The National Heart, Lung, and Blood
      Institute quality assessment tool was used for the quality assessment of included
      studies. Two hundred and eighteen records were retrieved through a literature
      search. Following the screening process, eight studies were included. According
      to the ratings of the quality assessment tool, four studies were classified as
      good and four were categorized as fair. The result of the current study reveals
      that LGIT has a beneficial effect in patients with intractable epilepsy. However,
      more high-quality studies are required to determine the efficacy of LGIT in
      patients with intractable epilepsy.

PMID- 29368116
TI  - Reliability and validity of telephonic Barthel Index: an experience from multi
      centric randomized control study.
AB  - Telephonic Barthel Index (BI) assessment is less time-consuming and more feasible
      than a face-to-face interview. The aim of this study was to test the validity as
      well as reliability of the BI administered by telephone in comparison with face
      to-face assessment in a multi-centric study. The study was conducted during the
      course of a randomized controlled trial in which 120 patients with subacute
      strokes from five teaching hospitals from different parts of India were
      recruited. Central telephonic follow-up and face-to-face assessment of BI and
      modified Rankin Scale (mRS) at 3 and 6 months were done by trained and certified
      blinded researchers. Kappa or weighted kappa (wK) was estimated. Sensitivity and
      specificity at various cutoff levels of telephonic BI were calculated. Concurrent
      validity of the telephonic BI was assessed by correlating it with the mRS and
      National Institutes of Health Stroke Scales (NIHSS) at 3 and 6 months. We
      observed high sensitivity and specificity at various cutoff levels of BI.
      Moderate to substantial agreement was observed between the two methods at 6
      months wK 0.72 (95% CI 0.70-0.77). Item-wise and center-wise kappa also reflected
      substantial agreement. The study shows that telephonic assessment of activities
      of daily living with the BI in moderate to severely disabled stroke patients is
      valid and reliable compared to face-to-face assessment. Our study shows that
      telephonic assessment requires smaller sample size compared to face-to-face
      assessment of BI.

PMID- 29368117
TI  - Beyond V40.31: Narrative Phenomenology of Wandering in Autism and Dementia.
AB  - Research on autism spectrum disorder (ASD) and on Alzheimer's Disease (AD) and
      other types of dementia describes a behaviour called 'wandering', a term that
      denotes movement through space lacking intention or exact destination, as when a
      person is disoriented or not self-aware. In the U.S., 'wandering' in both ASD and
      AD has been examined mostly from a management and prevention perspective. It
      prioritizes safety while primarily overlooking personal experiences of those who
      'wander' and their families, thus limiting the range of potentially effective
      strategies to address this issue. Communicative challenges faced by many people
      diagnosed with ASD and AD further obscure the experiential, existential aspects
      of 'wandering'. This article reflects an increasing concern of social science
      scholars interested in whether and how the conceptual and practical strategies to
      address 'wandering' are informed by the situated experiences of people with
      cognitive and developmental disabilities and their families. We examine
      'wandering' at the intersections of personal experience, family life, clinical
      practice, public health policy, and legislation, as a conceptually rich site
      where notions of personhood, subjectivity, intentionality, and quality of life
      powerfully and consequentially converge to impact the lives of many people with
      ASD and AD, and their families. We draw upon critical autism studies describing
      how attributions of personhood, subjectivity, intentionality, rational agency,
      and moral autonomy of people with ASD have been contingent upon the norms and
      conventions governing movement of the human body through space (Hilton, Afr Am
      Rev 50(2):221-235, 2017). When this movement is deemed aberrant, the person may
      be construed as irrational, a danger to self because of a lack of self-awareness,
      and a danger to others because of a lack of empathy. These attributions put the
      person at risk of being excluded from the considerations and, more importantly,
      the obligations of the 'moral community' to ensure that he or she has a 'good
      human life' (Barnbaum, The Ethics of Autism: Among Them but not of Them. Indiana
      University Press, Bloomington, 2008; Silvers and Francis, Metaphilosophy
      40(3/4):475-498, 2009). Using ethnographic, narrative phenomenological
      (Mattingly, The Paradox of Hope: Journeys through a Clinical Borderland.
      Berkeley: University of California Press, 2010), and medical humanities (Charon,
      JAMA 286:1897-1902, 2001; Narrative Medicine: Honoring the Stories of Illness.
      New York: Oxford University Press, 2006) approaches, we examine multiple
      perspectives on 'wandering' in ASD and AD across narrative discourse genres,
      institutional contexts, and media of representation. We argue for an extension of
      the prevention and management view to focus not only on safety but also on what
      phenomenologist Merleau-Ponty (1962) called "having a world" (p. 146). The
      analysis is intended to inform clinical practice, policy and public health
      efforts to enhance understanding of first and second person perspectives on
      'wandering' in order to improve the participation and quality of life of people
      with ASD and AD who 'wander', and their families.

PMID- 29368119
TI  - [German congress for healthcare research : Solutions and innovations for German
      health policy in the new legislative period].
AB  - The German congress for healthcare research reached a new historic record of 859
      participants from healthcare research, practice, and policy who visited the
      congress from 4-6 October 2017 to discuss developments, results, and innovations
      in healthcare research.The German healthcare system will face key challenges over
      the coming years. As the German population is getting older and disease incidence
      will become more complex, the number of healthcare professionals will
      simultaneously decrease.The experts provided solutions and innovations in 322
      lectures and in 239 poster presentations.Hot topics included innovative and cross
      sectoral healthcare concepts, patient safety, new forms of division of labor,
      telemedicine, eHealth as well as projects of the innovation fund and the Federal
      Ministry for Education and Research.Healthcare experts state that healthcare
      research is a key partner of patients, health policy, and self-government. The
      experts declare that future healthcare should be regional, cross-sectoral, and
      should include all healthcare professions. They formulate several demands on
      health policy for the new legislative period.

PMID- 29368118
TI  - A tribute to Ulrich Heber (1930-2016) for his contribution to photosynthesis
      research: understanding the interplay between photosynthetic primary reactions,
      metabolism and the environment.
AB  - The dynamic and efficient coordination of primary photosynthetic reactions with
      leaf energization and metabolism under a wide range of environmental conditions
      is a fundamental property of plants involving processes at all functional levels.
      The present historical perspective covers 60 years of research aiming to
      understand the underlying mechanisms, linking major breakthroughs to current
      progress. It centers on the contributions of Ulrich Heber who had pioneered novel
      concepts, fundamental methods, and mechanistic understanding of photosynthesis.
      An important first step was the development of non-aqueous preparation of
      chloroplasts allowing the investigation of chloroplast metabolites ex vivo
      (meaning that the obtained results reflect the in vivo situation). Later on,
      intact chloroplasts, retaining their functional envelope membranes, were isolated
      in aqueous media to investigate compartmentation and exchange of metabolites
      between chloroplasts and external medium. These studies elucidated metabolic
      interaction between chloroplasts and cytoplasm during photosynthesis. Experiments
      with isolated intact chloroplasts clarified that oxygenation of ribulose-1.5
      bisphosphate generates glycolate in photorespiration. The development of non
      invasive optical methods enabled researchers identifying mechanisms that balance
      electron flow in the photosynthetic electron transport system avoiding its over
      reduction. Recording chlorophyll a (Chl a) fluorescence allowed one to monitor,
      among other parameters, thermal energy dissipation by means of 'nonphotochemical
      quenching' of the excited state of Chl a. Furthermore, studies both in vivo and
      in vitro led to basic understanding of the biochemical mechanisms of freezing
      damage and frost tolerance of plant leaves, to SO2 tolerance of tree leaves and
      dehydrating lichens and mosses.

PMID- 29368120
TI  - [Requirements for CE-marking of apps and wearables].
AB  - Depending on the intended use, apps and wearables can be medical devices. In such
      cases, the manufacturer has to provide evidence that the requirements stated in
      directive 93/42/EWG are fulfilled. Depending on the classification of the medical
      device, several so-called conformity assessment procedures are possible. Once the
      conformity assessment procedure has been finished successfully, the manufacturer
      attaches the CE-marking to the product. This assures that all requirements of the
      directive have been fulfilled and the manufacturer is therefore authorized to put
      the product onto the market in all member states of the European union. In this
      article, the possible and practical conformity assessment procedures for apps and
      wearables are described and their implementation is outlined.For medical devices
      with sufficiently high-risk classification, the manufacturer has to involve a
      Notified Body. For the conformity assessment procedure according to annex II, the
      manufacturer implements a full quality management system and compiles technical
      documentation. These are supervised and evaluated by Notified Body audits.
      Especially for startups, it is important for the development of apps and
      wearables to implement a quality management system early and to fulfill the
      regulatory requirements, for example, related to the software life-cycle model.
      This also includes considering accompanying processes during development like
      risk management, usability engineering, and clinical evaluation.Additionally, it
      should be pointed out, that according to the new medical device regulation almost
      all apps will fall at least into class IIa. Thus, the involvement of a Notified
      Body in the related conformity assessment procedures would be required. Apps that
      have already been put onto the market as class I devices, and are now upgraded to
      a higher class, need the approval of a notified body starting from 26 May 2020.

PMID- 29368121
TI  - [Assessing the benefits of digital health solutions in the societal reimbursement
      context].
AB  - For a number of reasons, achieving reimbursability for digital health products
      has so far proven difficult. Demonstrating the benefits of the technology is the
      main hurdle in this context. The generally accepted evaluation processes,
      especially parallel group comparisons in randomized controlled trials (RCTs) for
      (clinical) benefit assessment, are primarily intended to deal with questions of
      (added) medical benefit. In contrast to drugs or classical medical devices, users
      of digital health solutions often profit from gaining autonomy, increased
      awareness and mindfulness, better transparency in the provision of care, and
      improved comfort, although there are also digital solutions with an
      interventional character targeting clinical outcomes (e. g. for indications such
      as anorexia, depression). Commonly accepted methods for evaluating (clinical)
      benefits primarily rely on medical outcomes, such as morbidity and mortality, but
      do not adequately consider additional benefits unique to digital health. The
      challenge is therefore to develop evaluation designs that respect the
      particularities of digital health without reducing the validity of the
      evaluations (especially with respect to safety). There is an increasing need for
      concepts that include both continuous feedback loops for adapting and improving
      an application while at the same time generate sufficient evidence for complex
      benefit assessments. This approach may help improve risk benefit ratio
      assessments of digital health when it comes to implementing digital innovations
      in healthcare.

PMID- 29368122
TI  - Native rotational knee kinematics are lost in bicruciate-retaining total knee
      arthroplasty when the tibial component is replaced.
AB  - PURPOSE: To compare the kinematics between native knees and knees that have
      undergone bicruciate-retaining (BCR) total knee arthroplasty (TKA) with cruciate
      retaining (CR) TKA converted from BCR TKA in the same whole-body cadaveric
      specimen using a navigation system and, if differences exist, to investigate the
      point at which normal kinematics are lost during the procedure. METHODS: The
      rotational kinematics throughout passive flexion of the native knee and of knees
      after meniscectomy, femoral replacement, BCR TKA, or CR TKA were assessed in nine
      fresh frozen cadavers using an image-free navigation system. RESULTS: The
      rotational kinematic pattern of a knee after BCR TKA was different from that of a
      native knee, especially in the early flexion phase, and was similar to that after
      CR TKA. Screw-home movement was not observed after BCR TKA, but still occurred
      after meniscectomy or femoral replacement with intact cruciate ligaments and an
      intact tibial articular surface. CONCLUSION: The rotational kinematics of the
      native knee are not always preserved after BCR TKA. Native rotational kinematics
      are preserved after meniscectomy and femoral replacement, but are lost after
      tibial replacement in BCR TKA. Surgeons should pay close attention to maintain
      the anteroposterior stabilizing function of the ACL in BCR TKA, rather than to
      restore the native rotational kinematics.

PMID- 29368123
TI  - Videodefecography is still superior to magnetic resonance defecography in the
      study of obstructed defecation syndrome.

PMID- 29368125
TI  - Overview of Current and Future First-Line Systemic Therapy for Metastatic Clear
      Cell Renal Cell Carcinoma.
AB  - OPINION STATEMENT: Treatment of metastatic clear cell renal cancer (mccRCC) has
      seen substantial progress over the last 20 years, with many regulatory approvals
      since 2006 culminating in a substantial increase to overall survival (OS). Six
      therapies are currently available for first-line use, with additional treatments
      currently being tested in this setting, some of which are expected to be approved
      soon based on new data from the CABOSUN and CheckMate-214 trials. Based on the
      available evidence, we strongly believe that vascular endothelial growth factor
      tyrosine kinase inhibitor (VEGF-TKI) therapy over mechanistic target or rapamycin
      (mTOR; formerly known as mammalian target of rapamycin) inhibitor therapy is the
      most effective first-line option regardless of risk category assignment. High
      dose interleukin-2 (HDIL-2) therapy remains a reasonable treatment option in
      patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-1
      and have minimal comorbid conditions. In the near future, these agents are likely
      to be surpassed by cabozantinib and by combination immune checkpoint inhibitor
      therapy with nivolumab and ipilimumab. Independent review has recently confirmed
      superiority of first-line cabozantinib over sunitinib in a phase 2 trial of 157
      patients with intermediate or poor risk mccRCC (progression-free survival [PFS]
      8.6 vs 5.3 months, hazard ratio [HR] 0.48, p = 0.0008). In a separate study of
      1096 patients treated with either upfront sunitinib or the combination of
      nivolumab and ipilimumab, those with intermediate and poor risk had significant
      improvement in both PFS (11.6 vs 8.4 months, HR 0.82, p = 0.0331) and OS (not
      reached vs 26 months, p < 0.0001). Responses were greater in patients with
      positive programmed death receptor ligand-1 (PD-L1) tumor staining, and pending
      regulatory approval may become standard of care in untreated patients with
      intermediate to poor risk disease with positive PD-L1 status. This likely
      represents the beginning of additional novel immunotherapy combinations for the
      first-line treatment of mccRCC.

PMID- 29368124
TI  - Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) advanced to cirrhosis is often
      complicated by clinically significant portal hypertension, which is primarily
      caused by increased intrahepatic vascular resistance. Liver fibrosis has been
      identified as a critical determinant of this process. However, there is evidence
      that portal venous pressure may begin to rise in the earliest stages of NAFLD
      when fibrosis is far less advanced or absent. The biological and clinical
      significance of these early changes in sinusoidal homeostasis remains unclear.
      Experimental and human observations indicate that sinusoidal space restriction
      due to hepatocellular lipid accumulation and ballooning may impair sinusoidal
      flow and generate shear stress, increasingly disrupting sinusoidal
      microcirculation. Sinusoidal endothelial cells, hepatic stellate cells, and
      Kupffer cells are key partners of hepatocytes affected by NAFLD in promoting
      endothelial dysfunction through enhanced contractility, capillarization, adhesion
      and entrapment of blood cells, extracellular matrix deposition, and
      neovascularization. These biomechanical and rheological changes are aggravated by
      a dysfunctional gut-liver axis and splanchnic vasoregulation, culminating in
      fibrosis and clinically significant portal hypertension. We may speculate that
      increased portal venous pressure is an essential element of the pathogenesis
      across the entire spectrum of NAFLD. Improved methods of noninvasive portal
      venous pressure monitoring will hopefully give new insights into the pathobiology
      of NAFLD and help efforts to identify patients at increased risk for adverse
      outcomes. In addition, novel drug candidates targeting reversible components of
      aberrant sinusoidal circulation may prevent progression in NAFLD.

PMID- 29368127
TI  - Efficacy and Safety of Tiotropium in Children and Adolescents.
AB  - Asthma is one of the most common chronic diseases in children, with a high
      proportion of patients demonstrating poor control despite the availability of
      disease management guidelines. Global Initiative for Asthma guidelines include
      tiotropium as an add-on therapy option at Steps 4 and 5 in patients aged >= 12
      years with a history of exacerbations, and tiotropium delivered via the
      Respimat(r) Soft MistTM Inhaler has recently been approved for use as once-daily
      maintenance therapy for children with asthma over the age of 6 years in the USA.
      A large clinical trial program has been conducted in children, adolescents, and
      adults across the spectrum of asthma severity. Findings from these clinical
      studies and pooled analyses in children and adolescents with symptomatic moderate
      or severe asthma have demonstrated that tiotropium Respimat(r) as add-on to
      inhaled corticosteroids, with or without other maintenance therapies, is a well
      tolerated and efficacious bronchodilator, showing improved lung function and
      trends towards improved asthma control, mirroring findings in adult studies. This
      review discusses the evidence to date for tiotropium Respimat(r) for the
      management of asthma in adolescents and children with symptomatic moderate and
      severe asthma, and considers the challenges of asthma management in these
      patients. Factors affecting this population group, such as poor adherence,
      underreporting of symptoms, and social and psychological issues, are highlighted,
      along with the need for active review and management of treatment to help achieve
      optimal control.

PMID- 29368128
TI  - Cadmium Profiles in Dental Calculus: a Cross-Sectional Population-Based Study in
      Hunan Province of China.
AB  - We aimed to investigate whether the cadmium concentrations differ in human dental
      calculus obtained from the residents with no smoking living in the contaminated
      area and those with no smoking living in noncontaminated area. In total, there
      were 260 samples of dental calculus from the adults (n = 50) with no smoking
      living in contaminated area, the adults (n = 60) with no smoking living in
      mountainous area, and the adults (n = 150) with no smoking living in low altitude
      area in Hunan province of China. All samples were analyzed by inductively coupled
      plasma mass spectrometry (ICP-MS) for cadmium levels. The cadmium levels in
      dental calculus were significantly higher in the adults with no smoking living in
      contaminated area than those living in mountainous area and in low altitude area
      (p < 0.01). The cadmium levels in dental calculus were also higher in the adults
      with no smoking living in low altitude area than those living in mountainous
      region (p < 0.01). The results suggested that measuring cadmium levels in dental
      calculus may be a useful noninvasive method for analysis of environmental
      exposure to cadmium in the human oral cavity. The low altitude region may have an
      area contaminated with cadmium in Hunan province of China.

PMID- 29368126
TI  - Pharmacotherapy for Refractory and Super-Refractory Status Epilepticus in Adults.
AB  - Patients with prolonged seizures that do not respond to intravenous
      benzodiazepines and a second-line anticonvulsant suffer from refractory status
      epilepticus and those with seizures that do not respond to continuous intravenous
      anesthetic anticonvulsants suffer from super-refractory status epilepticus. Both
      conditions are associated with significant morbidity and mortality. A strict
      pharmacological treatment regimen is urgently required, but the level of evidence
      for the available drugs is very low. Refractory complex focal status epilepticus
      generally does not require anesthetics, but all intravenous non-anesthetizing
      anticonvulsants may be used. Most descriptive data are available for
      levetiracetam, phenytoin and valproate. Refractory generalized convulsive status
      epilepticus is a life-threatening emergency, and long-term clinical consequences
      are eminent. Administration of intravenous anesthetics is mandatory, and drugs
      acting at the inhibitory gamma-aminobutyric acid (GABA)A receptor such as
      midazolam, propofol and thiopental/pentobarbital are recommended without
      preference for one of those. One in five patients with anesthetic treatment does
      not respond and has super-refractory status epilepticus. With sustained seizure
      activity, excitatory N-methyl-d-aspartate (NMDA) receptors are increasingly
      expressed post-synaptically. Ketamine is an antagonist at this receptor and may
      prove efficient in some patients at later stages. Neurosteroids such as
      allopregnanolone increase sensitivity at GABAA receptors; a Phase 1/2 trial
      demonstrated safety and tolerability, but randomized controlled data failed to
      demonstrate efficacy. Adjunct ketogenic diet may contribute to termination of
      difficult-to-treat status epilepticus. Randomized controlled trials are needed to
      increase evidence for treatment of refractory and super-refractory status
      epilepticus, but there are multiple obstacles for realization. Hitherto,
      prospective multicenter registries for pharmacological treatment may help to
      improve our knowledge.

PMID- 29368129
TI  - Two new gonad-infecting species of Philometra Costa, 1845 (Nematoda:
      Philometridae) from Trachinus spp. (Osteichthyes: Trachinidae) in the Gulf of
      Hammamet, Tunisia.
AB  - Based on light and scanning electron microscopical studies, two new gonad
      infecting species of Philometra Costa, 1845, P. draco n. sp. and P. radiata n.
      sp. (Nematoda: Philometridae), are described from the marine perciform fishes
      Trachinus draco (Linnaeus) and T. radiatus (Linnaeus) (both Trachinidae),
      respectively, in the Gulf of Hammamet, off the northeastern coast of Tunisia.
      Philometra draco n. sp. and P. radiata n. sp. can be separated from other gonad
      infecting species of this genus by the structures associated to the gubernaculum
      (e.g. dorsal protuberance, smooth field separating the dorsolateral longitudinal
      parts), as well as by the length of the body, spicules and gubernaculum.
      Philometra radiata n. sp. can be distinguished from P. draco n. sp. in having the
      dorsal side of the gubernaculum distal end provided with a median longitudinal
      smooth field demarcated by two dorsolateral lamellate parts. These two new
      species are the first philometrid species described from fishes of the family
      Trachinidae.

PMID- 29368130
TI  - Complete conversion of all typical glycosylated protopanaxatriol ginsenosides to
      aglycon protopanaxatriol by combined bacterial beta-glycosidases.
AB  - Aglycon protopanaxatriol (APPT) has valuable pharmacological effects such as anti
      inflammatory and anti-stress activities. However, the complete conversion of all
      typical glycosylated protopanaxatriol ginsenosides to APPT has not been achieved
      to date. beta-Glycosidase from the hyperthermophilic bacterium Dictyoglomus
      turgidum (DT-bgl) hydrolyzes the glucose residues at C-6 and the inner glucose at
      C-20 in protopanaxatriol (PPT), but not the outer rhamnose residues at C-6. In
      contrast, beta-glycosidase from the hyperthermophilic bacterium Pyrococcus
      furiosus (PF-bgl) hydrolyzes the outer rhamnose residue at C-6 but not the inner
      glucose residues at C-6 and C-20 in PPT. Thus, the combined use of DT-bgl and PF
      bgl resulted in the complete the conversion of all typical glycosylated PPT
      ginsenosides, including R1, R2, Re, Rg1, Rg2, Rh1, Rf, F1, F3, and F5, to APPT.
      DT-bgl combined with PF-bgl completely hydrolyzed 1.0 mg ml-1 R1 and 1.0 mg ml-1
      total PPT-type ginsenosides in Panax notoginseng root extract to 0.5 and 0.63 mg
      ml-1 APPT for 4 and 3 h, with molar conversions of 100% and productivities of 125
      and 210 mg l-1 h-1, respectively. To the best of our knowledge, this is the first
      report of the complete conversion of all typical glycosylated PPT ginsenosides to
      APPT and the highest productivity of APPT obtained from ginseng extract achieved
      to date.

PMID- 29368131
TI  - Public Awareness and Attitude Towards Depression: A Community Based Study Among
      an Adult Population in Ile-Ife South-Western Nigeria.
AB  - Depression has become a global health priority due to its associated burden.
      However, there is dearth of information regarding the public awareness and
      attitude towards depression in Nigeria. This study aimed to assess the level of
      public awareness and attitude towards depression in a semi-urban Nigerian
      community. A cross-sectional study conducted among 240 respondents with mean age
      of 34.7 years (+/- 1.2 years). A questionnaire assessed socio-demographic
      characteristics, level of awareness and attitude of people towards depression.
      While most respondents (72.5%) had heard about depression, it was less recognized
      as a major mental health problem. Also, most respondents (58.6%) had negative
      attitudes toward depression. There is low level of awareness of depression as a
      major health problem among community dwellers in South-western Nigeria and
      negative attitudes towards the illness also appear prevalent. Therefore,
      awareness should be improved through public health enlightenment programmes.

PMID- 29368132
TI  - Acceptability of Mental Health Services for Anxiety and Depression in an Arab
      Sample.
AB  - The aim of this paper was to examine the acceptability and use of mental health
      services in an Arab sample. An Internet survey was made available to Arab people
      worldwide and enquired about the acceptability of traditional face-to-face and
      internet-delivered mental health services. Five hundred and three participants
      were recruited via media and Facebook promotions. Of those surveyed, 36%
      (183/503), 46% (233/503), and 73% (365/503) reported that they would be willing
      to consult a mental health professional, take prescription medication and try an
      internet-delivered psychological treatment, respectively. Moderate to high
      acceptability rates for mental health services were found in this sample of Arab
      people. High acceptability of internet-delivered treatments among the current
      Arab sample, provides the opportunity for directing resources to the development
      of internet-delivered interventions to help reduce the stigma and burden of
      mental disease in the Arab world.

PMID- 29368133
TI  - "I Believe I Know Better Even than the Psychiatrists What Caused It": Exploring
      the Development of Causal Beliefs in People Experiencing Psychosis.
AB  - This study aimed to describe the causal beliefs of individuals experiencing
      psychosis, specifically exploring how they are developed and maintained.
      Individuals with experience of psychosis were recruited from mental health
      services for in-depth interviews. A thematic analysis was used to analyse
      transcripts and key themes were identified. Fifteen interviews were conducted.
      Individuals were engaged in the process of exploring explanations for their
      experiences and reported sophisticated models of causation. Participants
      described a change in their beliefs, with the cause of their experiences not
      immediately clear. Individuals generated their models via external (family,
      professionals) and internal (evaluative, positive affect) processes and reported
      differing levels of conviction in relation to their beliefs. Clinicians should
      take the opportunity to explore the causal beliefs of their service-users, as
      they are able to provide intelligent and thoughtful explanatory models. In
      particular, clinicians should be aware of the emotional impact of different
      aetiological models and their personal role in the development of a client's
      beliefs.

PMID- 29368134
TI  - Iron Oxide Nanoparticles Induces Cell Cycle-Dependent Neuronal Apoptosis in Mice.
AB  - Iron oxide (Fe2O3) nanoparticles (NPs) with its unique magnetic and paramagnetic
      properties are popular in biomedical applications. Some of their neurotoxic
      mechanisms due to repeated administration are proven. However, we speculate that
      the neuronal damage might be due to apoptosis resulting from unusual cell cycle
      entry. Moreover, iron accumulation has been shown to be closely associated with
      most of the neurodegenerative disorders. Thus, in the current study, mice were
      orally (po) treated with the Fe2O3-NPs to investigate cell cycle-associated
      events/components and occurrence of apoptosis. A subsequent increase in oxidant
      levels was observed with the iron accumulation due to Fe2O3-NPs exposure. The
      accumulated beta-amyloid and reduced level of cdk5 seem to aid in the cell cycle
      entry and forcing progression towards apoptosis. Expression of Cyclin D1 and pRb
      (Ser 795) indicate the cell cycle re-entry of neurons. Overexpression of RNA Pol
      II and PARP cleavage suggests DNA damage due to Fe2O3-NPs exposure. Further,
      hyperphosphorylation of p38 (Thr 180/Tyr 182) confirms the activation of DNA
      damage-dependent checkpoint. Expression patterns of pro- and anti-apoptotic
      markers, TUNEL and TEM indicate the occurrences of apoptosis.

PMID- 29368136
TI  - Evaluating the accuracy of microRNA27b and microRNA137 as biomarkers of activity
      and potential malignant transformation in oral lichen planus patients.
AB  - Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease with a
      potential malignant transformation, characterized by cytotoxic T cells against
      basal epithelial cells. MicroRNAs (MiRNAs) are short non-coding RNA that plays
      critical role in gene expression at post-transcriptional levels. Much evidence
      showed that miRNAs play an important role in regulating immune response and
      cancer development. The purpose of the present study was to compare the
      expression of miRNA 27b and miRNA 137 in tissues and saliva between OLP patients
      and controls by using RT-qPCR and to evaluate their use as biomarkers of disease
      activity and potential malignant transformation. Our results showed down
      expression of miRNA 27b and miRNA 137 in tissue and saliva of OLP patients
      compared to controls; among OLP subgroups, erosive-type miRNA 137 revealed the
      lowest level in tissue and saliva. In conclusion, alteration of miRNA 27b and
      miRNA 137 gene expression signify their use as biomarkers for diseases activity
      and tendency of malignant transformation, and down expression of miRNA 137
      especially in erosive-type favors the use of saliva sample as a noninvasive
      method for monitoring a potential malignant transformation of OLP.

PMID- 29368135
TI  - Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice
      identifies a role for IL-33 in disease pathogenesis.
AB  - The Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific
      expression of a constitutively active form of the protein signal transducer and
      activator of transcription 6 (STAT6). Although AD-like lesions are known to
      develop in Stat6VT mice, this study was designed to determine if these mice
      develop acute and chronic phases of disease similar to humans. To address this,
      AD-like lesions from Stat6VT mice were harvested at two different timepoints
      relative to their onset. Lesions harvested within 1 week after development were
      defined as acute lesions, and those present for 1 month or more were defined as
      chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited
      histologic findings and cytokine expression patterns similar to acute and chronic
      AD lesions in humans. Further analysis revealed increased levels of interleukin
      (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild
      type skin controls. Immunofluorescence also revealed increased numbers of IL-33+
      keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a
      keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33
      deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies
      suggest that Stat6VT mice can serve as a model of acute and chronic AD and that
      IL-33 may attenuate inflammation in this system.

PMID- 29368137
TI  - The 6MWT as a prognostic tool in pulmonary arterial hypertension: results from
      the COMPERA registry.
AB  - BACKGROUND: In patients with pulmonary arterial hypertension, the 6-Minute Walk
      Test (6MWT) is recommended for risk stratification and follow-up by all
      guidelines. However, the prognostic value of the 6MWT has been discussed
      controversially. We sought to compare and validate all published 6MWT cut-off
      points. METHODS: From the Comparative, Prospective Registry of Newly Initiated
      Therapies for Pulmonary Hypertension (COMPERA)-registry we identified 2391
      patients with pulmonary arterial hypertension who had at least one documented
      6MWT measurement. A Medline search identified a total of 21 different threshold
      values for either single-point or change of 6MWT. All values were tested
      individually for prognostication of 1-year, 2-year and 3-year all-cause
      mortality. RESULTS: The highest positive likelihood ratio was a cut-off value <
      165 ms, whereas the best negative likelihood ratio was found to be a threshold of
      440 ms. Furthermore, improvement in 6MWT had considerably less predictive value
      on mortality and survival than deterioration. Moreover, absolute single-point
      values outperformed change values for both improvement and worsening. CONCLUSION:
      Our data confirmed the prognostic relevance of the 6MWT and support the cut-off
      values stated in most recent guidelines. Furthermore, these results explain why
      changes in 6MWT did not correlate consistently with prognosis in previous
      studies.

PMID- 29368139
TI  - Hypertensive disorders during pregnancy and 3 years after delivery in women with
      gestational hyperglycemia.
AB  - AIMS: Women with gestational hyperglycemia commonly experience hypertensive
      disorders during pregnancy. More information is needed about how hypertension
      develops in these patients over time. We investigated the prevalence of
      hypertension during and 3 years after pregnancy in Caucasian women with
      gestational hyperglycemia. We also investigated metabolic syndrome presence,
      glucose tolerance status, insulin sensitivity and insulin secretion levels in the
      follow-up period. METHODS: In a prospective longitudinal study with a 3-year
      follow-up, we assessed hypertension status and clinical-related characteristics
      of 103 consecutive women with gestational hyperglycemia sub-grouped according to
      their hypertensive status during and after pregnancy. RESULTS: Overall, 29
      (28.1%) women had hypertension during pregnancy (24 gestational hypertension; 4
      chronic hypertension; 1 preeclampsia). At follow-up 16 (15.5%) women were
      diagnosed as having hypertension (11 with hypertension in pregnancy; 5 with a
      normotensive pregnancy). Women with hypertension after pregnancy had higher BMI,
      metabolic syndrome rate and worse insulin resistance indexes than normotensive
      women. Weight increase at follow-up (OR 1.17, 95% CI 1.00-1.35) and hypertension
      in pregnancy (OR 6.72, 95% CI 1.17-38.64) were associated with hypertension after
      pregnancy. CONCLUSIONS: Women with gestational hyperglycemia should undergo
      regular monitoring during and after pregnancy to detect metabolic and clinical
      impairments and to prevent cardiovascular harm.

PMID- 29368138
TI  - Sagittal balance and idiopathic scoliosis: does final sagittal alignment
      influence outcomes, degeneration rate or failure rate?
AB  - INTRODUCTION: In the last decade, spine surgeons have been impacted by the
      "sagittal plane analysis revolution". Significant correlations have been found in
      adult spinal deformity (ASD) between sagittal lumbo-pelvic parameters and
      functional outcomes, but most of them do not apply in adolescent idiopathic
      scoliosis (AIS). Meanwhile, instrumentation and reduction strategies have
      considerably evolved. This paper aims to describe the preoperative sagittal
      alignment in AIS, and to report literature evidence regarding the influence of
      postoperative sagittal balance on complication rates, low back pain incidence and
      disc degeneration. METHODS: A bibliographic search in Medline and Google database
      from 1984 to May 2017 was performed. The keywords included 'adolescent idiopathic
      scoliosis', 'adult scoliosis', 'sagittal alignment', 'proximal junctional
      kyphosis', 'distal junctional kyphosis', 'outcomes', 'low back pain' and
      'complication', used individually or in combination. RESULTS: Algorithms of
      sagittal balance analysis and treatment decision have been reported in ASD, but
      the clinical situation is very different in children. Sagittal alignment greatly
      varies in AIS among the various Lenke types. Most patients are clinically
      balanced before surgery, but the spinal harmony is altered, with overgrowth of
      the anterior column and global sagittal flattening (undersestimated in 2D). The
      exact role of pelvic incidence and whether or not patients also use pelvic
      compensation to maintain balance still require further clarification. The
      incidence of radiological junctional failures remains highly variable, depending
      on definitions, cohort size and follow-up. Preoperative hyperkyphosis seems to be
      a consistent and relevant risk factor. Current literature does not support the
      recent trend to save motion segments (selective fusion), and no significant
      association was found between the distal level of fusion and the incidence of low
      back pain. Postoperative sagittal alignment seems to be more important than LIV
      selection to avoid disc degeneration at mid-term follow-up. CONCLUSION: It is
      clear now that sagittal alignment plays a major role in clinical outcomes and
      should not be neglected in AIS. Seven key guidelines that should be considered
      for each patient before surgery are reported (Table 2). Personalized planning
      using 3D technology is gaining popularity and might help in the future reducing
      complications.

PMID- 29368140
TI  - Efficacy of a single session protocol for endodontic treatment in primary teeth:
      in vivo study.
AB  - AIMS: To determine the efficacy of a single session protocol (SSP) in the
      reduction of septic content of primary teeth root canals and identify the
      persistence of bacterial species associated with unsuccessful treatment. METHODS:
      Primary teeth root canals (16) with pulp necrosis and peri-radicular lesions were
      treated. Samples were collected at baseline (T1), and after chemo-mechanical
      preparation, before filling (T2). Identification of the microorganisms was
      determined using checkerboard DNA-DNA hybridisation. STATISTICAL ANALYSIS:
      Wilcoxon test was applied for comparison of mean number of species, proportion
      and mean count of each species between the evaluation times. RESULTS: Significant
      reductions were found in the mean number of bacteria species between T1 and T2 (p
      < 0.05), but not for the reduction in proportion (p > 0.05). There was a
      reduction (6.0-4.6) of the mean number of species associated with failure,
      without statistical significance. CONCLUSION: The SSP was capable of
      significantly reducing the septic content, even though, many of the bacteria
      associated with failure persisted at the time of root canal filling.

PMID- 29368141
TI  - The Effect of Bilingualism and Trilingualism on Metacognitive Processing:
      Detrimental or Beneficial?
AB  - Research in multilingualism has shown that bilinguals have enhanced executive
      function (e.g., Donnelly et al. in Proceedings of the 37th annual conference of
      the cognitive science society 2015; Green in Bilingualism Lang Cognit 1(02):67
      81, 1998. https://doi.org/10.1017/S1366728998000133 ); however, this with many
      other areas in multilingualism have been questioned like their non-verbal
      reasoning or their metacognitive ability. This study attempts to explore learning
      more than one languages in the field of metacognitive abilities. Three groups of
      monolinguals, bilinguals, and trilinguals were explored to examine the effect of
      language learning on enhancing or weakening accuracy and response time in
      metacognitive processing. Conducting dot discrimination task, we found that
      multilingualism might have some advantages in this field. As cognition and
      metacognitive abilities demonstrated no positive correlation in this study, we
      might conclude that executive functioning can not bring about higher order
      functioning for the individuals. Nevertheless, monolinguals did the task in the
      least period of time with the least accuracy. Trilinguals, on the contrary, could
      respond more accurately with an average speed. Accuracy, difficulty, and response
      time choice in metacognitive processing were discussed for each group. It is
      concluded that multilingualism might have different effects on higher-order
      decision making abilities.

PMID- 29368142
TI  - Family Planning and the Scope of the "Reproductive Psychiatry" Curriculum.

PMID- 29368143
TI  - Expression of three reporter genes in four cell lines developed from Papilio
      demoleus Linnaeus (Lepidoptera: Papilionidae).
AB  - This paper used recombinant baculoviruses that carried three reporter genes,
      green fluorescent protein (GFP), beta-galactosidase, and secreted alkaline
      phosphatase (SEAP), to infect four new cell lines from Papilio demoleus Linnaeus
      larvae (named RIRI-PaDe-1, RIRI-PaDe-2, RIRI-PaDe-3, and RIRI-PaDe-4). The
      expression levels of the three recombinant proteins were detected at 24, 48, 72,
      96, 120, and 144 h after infection and compared with Sf9 and High Five cells to
      evaluate the characteristics of these four cell lines as host cells. The
      inoculation densities of the tested cell lines were 2 * 104 cells/well (96-well
      plate) and 1 * 105 cells/well (24-well plate), and adding a volume of virus stock
      resulted in an MOI of 5.0. The results showed that the four cell lines could be
      infected by recombinant baculovirus and that cell lysis occurred 96 h after
      infection. In the four tested cell lines, only a small number of RIRI-PaDe-1 and
      RIRI-PaDe-3 cells expressed recombinant GFP and showed green fluorescence. The
      expression was much lower than that of Sf9 and High Five. Comparing the
      intracellular and extracellular activity of beta-galactosidase indicated that the
      P. demoleus cell system was more suitable for the expression of secreted
      proteins, and its extracellular beta-galactosidase level was close to that of
      Sf9, but the expression level of SEAP was far lower than those of Sf9 and High
      Five.

PMID- 29368144
TI  - Predictive and prognostic clinical and pathological factors of nivolumab efficacy
      in non-small-cell lung cancer patients.
AB  - BACKGROUND: Immunotherapy increases overall response rate (ORR) and overall
      survival (OS) in patients with non-small-cell lung cancer (NSCLC). Prognostic and
      predictive factors are a high need. PATIENTS AND METHODS: Retrospective review of
      NSCLC patients treated with nivolumab was performed. Analyzed variables included
      age, sex, stage, performance status (PS), location of metastases, presence of
      tumour-related symptoms and comorbidities, number of metastasis locations,
      previous chemotherapy, anti-angiogenic and radiotherapy treatments, and
      analytical data from the standard blood count and biochemistry. RESULTS: A total
      of 175 patients were included. Median age was 61.5 years, 73.1% were men, 77.7%
      were ECOG-PS 0-1, and 86.7% were included with stage IV disease. Histology was
      non-squamous in 77.1%. Sixty-five received nivolumab in second line (37.1%).
      Thirty-eight patients had brain metastasis (22%), and 39 (22.3%) liver metastasis
      and 126 (72%) had more than one metastatic location. The ORR was 15.7% with
      median Progression free survival (PFS) 2.8 months and median OS 5.81 months.
      Stage III vs IV and time since the beginning of the previous line of treatment >=
      6 vs < 6 months were associated with better response. PS 2, time since the
      previous line of treatment < 6 vs >= 6 months, and more than one metastatic
      location were independently associated with shorter OS in multivariable analysis
      (7.8 vs 2.7 months, 11.2 vs 4.6 months, and 9.4 vs 5.1 month). Finally, time
      since the previous treatment < 6 vs >= 6 months and more than one metastatic
      location were independently associated with shorter PFS in multivariable analysis
      (4.3 vs 2.3 months and 4.7 vs 2.3 months). CONCLUSION: Poor PS, short period of
      time since the previous treatment, and more than one metastatic location were
      associated with poorer prognostic.

PMID- 29368145
TI  - Combination of Oxaliplatin and Vit.E-TPGS in Lipid Nanosystem for Enhanced
      Therapeutic Efficacy in Colon Cancers.
AB  - PURPOSE: The main aim of present study was to prepare the oxaliplatin (OXL)
      loaded D-alpha-Tocopherol polyethylene glycol 1000 succinate (TPGS)-based lipid
      nanoparticles to enhance the anticancer effect in colon cancer cells. METHODS:
      The nanoparticles were nanosized and spherical shaped and exhibited controlled
      release kinetics. Flow cytometer and confocal laser scanning microscopy (CLSM)
      showed a remarkable uptake of nanoparticles in cancer cells in a time-dependent
      manner. RESULTS: The presence of TPGS remarkably increased the anticancer effect
      of OXL in HT-29 colon cancer cells. The IC50 value of free OXL was 4.25 MUg/ml
      whereas IC50 value of OXL-loaded TPGS-based lipid nanoparticles (OXL/TLNP) was
      1.12 MUg/ml. The 3-fold lower IC50 value of OXL/TLNP indicates the superior
      anticancer effect of nanoparticle-based OXL. Consistently, OXL/TLNP induced a
      remarkable apoptosis of cancer cells. Approximately, ~52% of cells were in early
      apoptosis phase and ~13% of cells were in late apoptosis phase indicating the
      potent anticancer effect of the formulations. The findings from this study
      provide novel insights into the use of TPGS and lipid nanoparticle together for
      the better antitumor effect in colon cancers. Future studies will involve the
      detailed in vitro and in vivo studies on clinically relevant animals.

PMID- 29368146
TI  - Irritant-induced asthma to hypochlorite in mice due to impairment of the airway
      barrier.
AB  - : Inhalation of commonly present irritants, such as chlorine and chlorine
      derivatives, can cause adverse respiratory effects, including irritant-induced
      asthma (IIA). We hypothesize that due to airway barrier impairment, exposure to
      hypochlorite (ClO-) can result in airway hypersensitivity. C57Bl/6 mice received
      an intra-peritoneal (i.p.) injection of the airway damaging agent naphthalene
      (NA, 200 mg/kg body weight) or vehicle (mineral oil, MO). In vivo micro-computed
      tomography (CT) images of the lungs were acquired before and at regular time
      points after the i.p. TREATMENT: After a recovery period of 14 days an intranasal
      (i.n.) challenge with 0.003% active chlorine (in ClO-) or vehicle (distilled
      water, H2O) was given, followed by assessment of the breathing frequency. One day
      later, pulmonary function, along with pulmonary inflammation was determined. Lung
      permeability was assessed by means of total broncho-alveolar lavage (BAL) protein
      content and plasma surfactant protein (SP)-D levels. In vivo micro-CT imaging
      revealed enlargement of the lungs and airways early after NA treatment, with a
      return to normal at day 14. When challenged i.n. with ClO-, NA-pretreated mice
      immediately responded with a sensory irritant response. Twenty-four hours later,
      NA/ClO- mice showed airway hyperreactivity (AHR), accompanied by a neutrophilic
      and eosinophilic inflammation. NA administration followed by ClO- induced airway
      barrier impairment, as shown by increased BAL protein and plasma SP-D
      concentrations; histology revealed epithelial denudation. These data prove that
      NA-induced lung impairment renders the lungs of mice more sensitive to an airway
      challenge with ClO-, confirming the hypothesis that incomplete barrier repair,
      followed by irritant exposure results in airway hypersensitivity.

PMID- 29368147
TI  - Cytochrome b 5 impacts on cytochrome P450-mediated metabolism of benzo[a]pyrene
      and its DNA adduct formation: studies in hepatic cytochrome b 5 /P450 reductase
      null (HBRN) mice.
AB  - Benzo[a]pyrene (BaP) is an environmental pollutant that, based on evidence
      largely from in vitro studies, exerts its genotoxic effects after metabolic
      activation by cytochrome P450s. In the present study, Hepatic Reductase Null
      (HRN) and Hepatic Cytochrome b 5 /P450 Reductase Null (HBRN) mice have been used
      to study the role of P450s in the metabolic activation of BaP in vivo. In HRN
      mice, cytochrome P450 oxidoreductase (POR), the electron donor to P450, is
      deleted specifically in hepatocytes. In HBRN mice the microsomal haemoprotein
      cytochrome b 5 , which can also act as an electron donor from cytochrome b 5
      reductase to P450s, is also deleted in the liver. Wild-type (WT), HRN and HBRN
      mice were treated by i.p. injection with 125 mg/kg body weight BaP for 24 h.
      Hepatic microsomal fractions were isolated from BaP-treated and untreated mice.
      In vitro incubations carried out with BaP-pretreated microsomal fractions, BaP
      and DNA resulted in significantly higher BaP-DNA adduct formation with WT
      microsomal fractions compared to those from HRN or HBRN mice. Adduct formation
      (i.e. 10-(deoxyguanosin-N2-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP [dG-N2
      BPDE]) correlated with observed CYP1A activity and metabolite formation (i.e. BaP
      7,8-dihydrodiol) when NADPH or NADH was used as enzymatic cofactors. BaP-DNA
      adduct levels (i.e. dG-N2-BPDE) in vivo were significantly higher (~ sevenfold)
      in liver of HRN mice than WT mice while no significant difference in adduct
      formation was observed in liver between HBRN and WT mice. Our results demonstrate
      that POR and cytochrome b 5 both modulate P450-mediated activation of BaP in
      vitro. However, hepatic P450 enzymes in vivo appear to be more important for BaP
      detoxification than its activation.

PMID- 29368148
TI  - The determination of zearalenone and its major metabolites in endometrial cancer
      tissues.
AB  - Endometrial cancer is one of the most commonly diagnosed cancers in women. The
      search for factors that contribute to the development of cancer cells in
      reproductive organs should involve the detection of xenoestrogens, in particular
      zearalenone (ZEA) and its metabolites. Xenoestrogens are endocrine disruptors-ZEA
      and its metabolites are structurally similar to estrogens (macrocyclic lactone
      ring) and show high affinity for estrogen receptors. This study proposes a new
      method for the preparation of samples of human tissues with endometrial cancer by
      the use of the QuEChERS technique. Analytical parameters such as centrifugation
      temperature, extraction solvent, and adsorbents were modified to obtain
      satisfactory recovery for ZEA (R = 82.6%, RSD = 2.9%) and one of its metabolites,
      alpha-zearalenol (R = 50.1%, RSD = 3.2%). High-performance liquid chromatography
      (HPLC) with fluorescence detection and tandem mass spectrometry (LC-QTOF-MS) were
      used for the identification and quantitative determination of the analyzed
      compounds. The developed procedure was applied for analyses of human tissues with
      endometrial cancer. The presence of alpha-zearalenol was detected in 47 out of
      the 61 examined tissue samples. Graphical Abstract Methodology for isolation and
      identification of zearalenone and its major metabolites.

PMID- 29368149
TI  - Gold nanoparticle-based colorimetric sensing of dipicolinic acid from complex
      samples.
AB  - Dipicolinic acid (DPA) can cause neurotoxicity and is abundant in bacterial
      spores. Although analytical methods have been reported for DPA detection with
      high sensitivity, their selectivity toward DPA is declined greatly in the
      presence of phosphates in the samples. In this study, we developed an approach
      for DPA detection that is not affected by the presence of phosphates. A
      colorimetric method based on the use of gold nanoparticles (AuNP) complexed with
      Ca2+ as sensing agents was explored for DPA detection. Calcium ions and
      glutathione-capped gold nanoparticles (AuNPs@GSH) can easily form complexes (Ca2+
      AuNP@GSH) through GSH-Ca2+ chelation, leading to the aggregation of AuNPs@GSH.
      The aggregation resulting from the complexes of AuNPs@GSH and Ca2+ can be
      reversed with the addition of DPA owing to the high formation constant (log Kf =
      4.4) between DPA and Ca2+. Furthermore, the color of AuNPs@GSH changes from red
      to purple when complexed with Ca2+, returning to red upon addition of DPA. The
      limit of detection of this sensing method toward DPA was estimated to be as low
      as ~ 2 MUM. The feasibility of using the sensing method for quantitative
      detection of DPA in soil and Bacillus cereus spore samples was also demonstrated.
      Graphical abstract A AuNP-based colorimetric sensing method against dipicolinic
      acid is developed.

PMID- 29368150
TI  - Application of solvent floatation to separation and determination of triazine
      herbicides in honey by high-performance liquid chromatography.
AB  - Based on the foaming property of the honey, a rapid, simple, and effective method
      solvent floatation (SF) was developed and firstly applied to the extraction and
      separation of triazine herbicides in honey. The analytes were determined by high
      performance liquid chromatography. Some parameters affecting the extraction
      efficiencies, such as the type and volume of extraction solvent, type of salt,
      amount of (NH4)2SO4, pH value of sample solution, gas flow rate, and floatation
      time, were investigated and optimized. The limits of detection for analytes are
      in the range of 0.16-0.56 MUg kg-1. The recoveries and relative standard
      deviations for determining triazines in five real honey samples are in the range
      of 78.2-112.9 and 0.2-9.2%, respectively.

PMID- 29368152
TI  - A Predictive Model for Axillary Node Pathologic Complete Response after
      Neoadjuvant Chemotherapy for Breast Cancer.
AB  - BACKGROUND: Recent trials have suggested the feasibility of performing a sentinel
      lymph node biopsy (SNB) following neoadjuvant chemotherapy (NAC). The selection
      of suitable patients for this approach remains controversial. We developed a
      predictive model to identify patients most likely to benefit from SNB following
      NAC. METHODS: The National Cancer Data Base was used to identify patients with
      clinically node positive (cN+) breast cancer undergoing NAC followed by breast
      surgery and axillary lymph node dissection (ALND). Patients were randomly
      assigned to a 70% testing or 30% validation cohort for model development. A
      predictive model was built based on significant factors associated with
      pathologic nodal response (pN0) and breast response. RESULTS: Using the testing
      cohort (n = 13,396), multivariate regression was used to identify predictors of
      pN0 based on preoperative factors. Younger age, hormone receptor (HR)
      negative/Her2-negative, HR-positive/Her2-positive, HR-negative/Her2-positive,
      high-grade, ductal histology, cN1 versus cN2, and extent of breast response were
      all significant independent predictors of pN0 on adjusted analysis. The odds
      ratios translated into a 10-point scale correlating to a stepwise increase in pN0
      response. The area under the curve for the ROC curves for the testing and
      validation cohorts was 0.781 and 0.788, respectively (p < 0.01). CONCLUSIONS: Our
      model incorporates known preoperative factors to predict the likelihood of pN0
      response in patients with cN+ disease who undergo NAC. For patients with high
      scores, SNB should be considered over ALND, because these patients have a greater
      likelihood of having negative nodes at final pathology.

PMID- 29368151
TI  - The impact of pre and perinatal lifestyle factors on child long term health and
      social outcomes: a systematic review.
AB  - To understand the full extent of the impact of a trial, it is important to
      consider the long-term consequences of outcomes beyond the trial follow-up
      period, especially for early year's interventions. A systematic review of the
      literature associated with the long-term consequences of four key outcomes from
      the Building Blocks trial, specifically, low birth weight, smoking during
      pregnancy, interval to subsequent pregnancy and A&E attendance or inpatient
      admission was conducted. These factors were guided by the funders, the Department
      of Health, as being of particular interest in the UK context. Relevant studies
      were identified from a number of sources including large databases, reference
      checking and citation searching. The search yielded 3665 papers, 43 of which were
      considered appropriate for inclusion. Of these, 29 were relating to smoking
      during pregnancy, 13 to low birth weight, 0 to A&E attendances during early
      childhood and 1 to short (< 2 years) interval to subsequent pregnancy. Consistent
      associations were found between maternal smoking during pregnancy and the effects
      this has on children's health, educational attainment and likelihood of engaging
      in problem behaviour and criminal activity in later life. Low birth weight was
      also found to impact on children's long-term health and cognitive development.
      Subsequent pregnancies within two years of the previous birth were linked with
      increased likelihood of pre-term birth and neonatal death. Only minimal evidence
      was identified regarding the consequences of a short interval to second pregnancy
      and of child A&E and outpatient attendances. Given that these outcomes have been
      identified by the UK Department of Health as of particular interest for UK
      benefit, investment of research in these areas is recommended to establish a
      clearer picture of both short and long-term consequences.

PMID- 29368153
TI  - Predictors for Use of Sentinel Node Biopsy and the Association with Improved
      Survival in Melanoma Patients Who Have Nodal Staging.
AB  - BACKGROUND: It is unknown how many patients with localized melanoma undergo
      sentinel lymph node biopsy (SLNB) or if there is a therapeutic effect from
      performing nodal staging. We evaluated predictors for SLNB use and assessed if
      there was an association with improved survival in melanoma patients who had
      SLNB. METHODS: The Surveillance, Epidemiology, and End Results database was
      queried for clinically node-negative melanoma cases >= 0.75 mm in thickness
      treated from 2010 to 2012. Clinicopathologic factors were correlated with SLNB
      use, overall survival (OS), and melanoma-specific survival (MSS). RESULTS:
      Overall, 13,703 cases were included. SLNB was performed in 1479 of 3439 thin
      cases (43.0%), 5810 of 8522 intermediate-thickness cases (68.2%), and 916 of 1742
      thick cases (52.6%). On multivariable analysis, age >= 70 years, thickness < 1 or
      > 4 mm, head/neck or trunk tumor location, being unmarried, African American
      race, and residing in a county with a lower level of education were significantly
      associated with a lower likelihood of performing SLNB (p < 0.05). Patients with
      intermediate-thickness or thick melanoma who had a SLNB had significantly
      improved OS and MSS compared with patients who did not have a SLNB (p < 0.05). On
      multivariable analysis, SLNB use significantly predicted for improved OS and MSS
      (p < 0.01). CONCLUSIONS: Only 68.2% of intermediate-thickness and 52.6% of thick
      melanomas are treated with SLNB. Age, thickness, tumor location, race, marital
      status, and socioeconomic factors appear to influence the performance of SLNB.
      This data becomes more relevant with the finding that SLNB use is potentially
      associated with improved survival.

PMID- 29368154
TI  - Author Correction: Characterization of Truncated dsz Operon Responsible for
      Dibenzothiophene Biodesulfurization in Rhodococcus sp. FUM94.
AB  - The original version of this article unfortunately contained a mistake in the
      caption of Figs. 5 and 6.

PMID- 29368155
TI  - NK/T Cell Lymphoma: Updates in Therapy.
AB  - PURPOSE OF REVIEW: Extranodal NK/T cell lymphoma (ENKL), nasal type, is a highly
      aggressive lymphoma which used to show a poor clinical outcome. Expression of P
      glycoprotein on lymphoma cells of ENKL is a major reason for the refractoriness
      to conventional chemotherapy containing anthracycline. However, recent innovative
      approaches have improved the outcome and prognosis of ENKL. The purpose of this
      review is to summarize the proceedings of treatment. RECENT FINDINGS: Concurrent
      chemoradiotherapy containing platinum and several drugs including L-asparaginase,
      methotrexate, and alkylators shows excellent outcomes for the limited-stage ENKL.
      SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) or other
      L-asparaginase-containing therapy is promising for advanced-stage ENKL, followed
      by either autologous or allogeneic hematopoietic stem cell transplantation. Anti
      PD-1 or other immunological checkpoint inhibitors are recently reported to be
      effective for relapsed/refractory ENKL thought to be due to EBV-driven
      upregulation of PD-L1 expression. The prognosis of ENKL is therefore improving by
      the introduction of these strategies. The 5-year overall survival (OS) rate of
      limited stage was 63.2% [95% confidence interval (CI), 55.3 to 70.0%] before
      2010, but was 79.4% (95% CI, 66.9 to 87.6%) in 2010 or after. However, there
      still exists a room for improvement, particularly for advanced-stage patients.
      The 2-year OS of advanced ENKL was 30.3% (95% CI, 19.5 to 41.7%) before 2010, but
      was 40.5% (95% CI, 24.8 to 55.8%) in 2010 or after. Optimal treatment scheme
      should further be explored.

PMID- 29368156
TI  - HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing.
AB  - AIMS/HYPOTHESIS: The aim of the study was to evaluate longitudinal associations
      between HbA1c levels, diabetes status and subsequent cognitive decline over a 10
      year follow-up period. METHODS: Data from wave 2 (2004-2005) to wave 7 (2014
      2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive
      function was assessed at baseline (wave 2) and reassessed every 2 years at waves
      3-7. Linear mixed models were used to evaluate longitudinal associations.
      RESULTS: The study comprised 5189 participants (55.1% women, mean age 65.6 +/-
      9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6
      13.7%). The mean follow-up duration was 8.1 +/- 2.8 years and the mean number of
      cognitive assessments was 4.9 +/- 1.5. A 1 mmol/mol increment in HbA1c was
      significantly associated with an increased rate of decline in global cognitive z
      scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005
      SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008
      SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total
      cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive
      protein, BMI, education, marital status, depressive symptoms, current smoking,
      alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer.
      Compared with participants with normoglycaemia, the multivariable-adjusted rate
      of global cognitive decline associated with prediabetes and diabetes was
      increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI 
      0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive
      function and orientation z scores showed an increased rate of cognitive decline
      with diabetes. CONCLUSIONS/INTERPRETATION: Significant longitudinal associations
      between HbA1c levels, diabetes status and long-term cognitive decline were
      observed in this study. Future studies are required to determine the effects of
      maintaining optimal glucose control on the rate of cognitive decline in people
      with diabetes.

PMID- 29368157
TI  - Fluorescence Correlation Spectroscopy with Photobleaching Correction in Slowly
      Diffusing Systems.
AB  - Fluorescence correlation spectroscopy (FCS) is a powerful tool to quantitatively
      study the diffusion of fluorescently labeled molecules. It allows in principle
      important questions of macromolecular transport and supramolecular aggregation in
      living cells to be addressed. However, the crowded environment inside the cells
      slows diffusion and limits the reservoir of labeled molecules, causing artifacts
      that arise especially from photobleaching and limit the utility of FCS in these
      applications. We present a method to compute the time correlation function from
      weighted photon arrival times, which compensates computationally during the data
      analysis for the effect of photobleaching. We demonstrate the performance of this
      method using numerical simulations and experimental data from model solutions.
      Using this technique, we obtain correlation functions in which the effect of
      photobleaching has been removed and in turn recover quantitatively accurate mean
      square displacements of the fluorophores, especially when deviations from an
      ideal Gaussian excitation volume are accounted for by using a reference
      calibration correlation function. This allows quantitative FCS studies of
      transport processes in challenging environments with substantial photobleaching
      like in living cells in the future.

PMID- 29368158
TI  - Fluorescent Carbon Dots as Cost-Effective and Facile Probes for Caffeic Acid
      Sensing via a Fluorescence Quenching Process.
AB  - Caffeic acid (CA), a familiar color stabilizing reagent, has aroused general
      concern due to its uncontrolled addition, and thus the detection of CA is
      increasingly important. In our report, the bright carbon dots (CDs) were prepared
      via hydrothermal treatment with urea and citric acid act as raw material and
      their characteristics were discussed through X-ray diffraction (XRD),
      transmission electron microscopy (TEM) and so on. Impressively, the strong
      emission of the as-prepared CDs (Quantum Yield: 24.3%) decreased sharply upon a
      full reaction with the added CA. Hence, we first present an improved strategy for
      determining CA based upon the quenching of the strong emission of CDs. In this
      strategy, 0.79-100.0 umol L- 1 caffeic acid could be simply detected, and a
      detection limit of 0.24 umol L- 1 was allowed. Additionally, CA in red wine
      samples can be successfully detected by this method and the exploration of the
      quenching mechanism of the CA-CDs system was done.

PMID- 29368159
TI  - [Distal radius fractures : Update on imaging].
AB  - Distal radius fractures are associated with high individual and socioeconomic
      relevance. Optimized radiography and computed tomography (CT) imaging are
      essential for individualized therapy planning. Plain CT imaging with 3D
      reconstruction and digital removal of the carpus and ulna is helpful for choosing
      the surgical approach in the presence of intra-articular radius fractures. If the
      fracture line leads towards the scapholunate compartment, ligamentous injury
      requiring treatment can be detected or ruled out before surgery with the help of
      direct CT arthrography (CTA). Acquisition of imaging data and morphometrical
      analysis must be standardized and reproducible. In the diagnostics of distal
      radius fractures it is necessary for radiologists and surgeons to use a unified
      fracture classification.

PMID- 29368160
TI  - Prognostic roles of neutrophil to lymphocyte ratio and platelet to lymphocyte
      ratio in ovarian cancer: a meta-analysis of retrospective studies.
AB  - PURPOSE: The systemic inflammatory response markers have been reported to be
      associated with the prognosis of various cancers. We conducted this meta-analysis
      of retrospective studies to evaluate and identify the prognostic impact of
      neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) on
      ovarian cancer. METHODS: PubMed, EMBASE, and China National Knowledge
      Infrastructure databases were included to search for eligible studies. The
      following terms were used: "neutrophil to lymphocyte ratio", "NLR", "platelet to
      lymphocyte ratio", "PLR", "ovarian cancer", "ovary cancer", "ovarian carcinoma",
      "ovary carcinoma", "ovarian neoplasm", "ovary neoplasm", "ovarian tumor", and
      "ovary tumor". The random-effects model was chosen to estimate the pooled HR with
      95% CI. Heterogeneity between studies was assessed by Higgins I2 value. The
      stability and heterogeneity of studies were analyzed by sensitivity analysis.
      Publication bias was examined by Egger's test and Begg's test with the funnel
      plots. RESULTS: 13 studies consisting of 3467 patients were considered for meta
      analysis. We found that the high NLR had a poor prognostic impact on OS and PFS
      in ovarian cancer, with a pooled HR 1.70, 95% CI 1.35-2.15 and HR 1.77, 95% CI
      1.48-2.12, respectively. Similarly, the results showed the high PLR adversely
      affected OS and PFS in ovarian cancer, with a pooled HR 2.05, 95% CI 1.70-2.48
      and HR 1.85, 95% CI 1.53-2.25, respectively. CONCLUSION: In conclusion, we found
      that both NLR and PLR had an unfavorable impact on PFS and OS of patients with
      ovarian cancer. Our meta-analysis supported that NLR/PLR could be effective
      prognostic predictors of ovarian cancer.

PMID- 29368161
TI  - Prediction of spontaneous ureteral stone passage: Automated 3D-measurements
      perform equal to radiologists, and linear measurements equal to volumetric.
AB  - OBJECTIVES: To compare the ability of different size estimates to predict
      spontaneous passage of ureteral stones using a 3D-segmentation and to investigate
      the impact of manual measurement variability on the prediction of stone passage.
      METHODS: We retrospectively included 391 consecutive patients with ureteral
      stones on non-contrast-enhanced CT (NECT). Three-dimensional segmentation size
      estimates were compared to the mean of three radiologists' measurements. Receiver
      operating characteristic (ROC) analysis was performed for the prediction of
      spontaneous passage for each estimate. The difference in predicted passage
      probability between the manual estimates in upper and lower stones was compared.
      RESULTS: The area under the ROC curve (AUC) for the measurements ranged from 0.88
      to 0.90. Between the automated 3D algorithm and the manual measurements the 95%
      limits of agreement were 0.2 +/- 1.4 mm for the width. The manual bone window
      measurements resulted in a > 20 percentage point (ppt) difference between the
      readers in the predicted passage probability in 44% of the upper and 6% of the
      lower ureteral stones. CONCLUSIONS: All automated 3D algorithm size estimates
      independently predicted the spontaneous stone passage with similar high accuracy
      as the mean of three readers' manual linear measurements. Manual size estimation
      of upper stones showed large inter-reader variations for spontaneous passage
      prediction. KEY POINTS: * An automated 3D technique predicts spontaneous stone
      passage with high accuracy. * Linear, areal and volumetric measurements performed
      similarly in predicting stone passage. * Reader variability has a large impact on
      the predicted prognosis for stone passage.

PMID- 29368162
TI  - Hepatic neuroendocrine tumour: Apparent diffusion coefficient as a potential
      marker of prognosis associated with tumour grade and overall survival.
AB  - OBJECTIVES: To evaluate the correlation between grade of hepatic neuroendocrine
      tumours (NETs) according to the 2010 World Health Organization (WHO)
      classification and the apparent diffusion coefficient (ADC) and to assess whether
      ADC value can predict overall survival (OS) after diagnosis of hepatic NETs.
      METHODS: The study included 63 patients who underwent magnetic resonance (MR)
      imaging with diffusion-weighted images for the evaluation of hepatic NETs. The
      correlation between qualitative and quantitative MR imaging findings, including
      ADC values, and WHO classifications was assessed. The association between ADC
      value and OS was analyzed. RESULTS: The ADC values and WHO classification of
      hepatic NETs were moderately negatively correlated in a statistically significant
      manner (rho = -0.57, p < 0.001). The OS rates were significantly different
      according to the ADC value (low ADC vs. high ADC, p = 0.006) as well as WHO
      classifications (G1+ G2 vs. G3, p = 0.038). However, multivariate analysis
      revealed that the only independent predictor for OS was a low ADC value (hazard
      ratio: 3.37, p = 0.010). CONCLUSION: There was a significant correlation between
      the ADC value of hepatic NETs and the WHO tumour grade. Additionally, the ADC
      value of a hepatic NET might be more accurate than the current WHO tumour grade
      for predicting OS. KEY POINTS: * ADC values of hepatic NET and WHO tumour grade
      were negatively correlated. * Lower ADC values of hepatic NET were significantly
      correlated with worse OS. * ADC value might be more accurate than WHO grade for
      predicting OS.

PMID- 29368163
TI  - Assessment of image quality in abdominal CT: potential dose reduction with model
      based iterative reconstruction.
AB  - PURPOSE: To estimate potential dose reduction in abdominal CT by visually
      comparing images reconstructed with filtered back projection (FBP) and strengths
      of 3 and 5 of a specific MBIR. MATERIAL AND METHODS: A dual-source scanner was
      used to obtain three data sets each for 50 recruited patients with 30, 70 and
      100% tube loads (mean CTDIvol 1.9, 3.4 and 6.2 mGy). Six image criteria were
      assessed independently by five radiologists. Potential dose reduction was
      estimated with Visual Grading Regression (VGR). RESULTS: Comparing 30 and 70%
      tube load, improved image quality was observed as a significant strong effect of
      log tube load and reconstruction method with potential dose reduction relative to
      FBP of 22-47% for MBIR strength 3 (p < 0.001). For MBIR strength 5 no dose
      reduction was possible for image criteria 1 (liver parenchyma), but dose
      reduction between 34 and 74% was achieved for other criteria. Interobserver
      reliability showed agreement of 71-76% (kappaw 0.201-0.286) and intra-observer
      reliability of 82-96% (kappaw 0.525-0.783). CONCLUSION: MBIR showed improved
      image quality compared to FBP with positive correlation between MBIR strength and
      increasing potential dose reduction for all but one image criterion. KEY POINTS:
      * MBIR's main advantage is its de-noising properties, which facilitates dose
      reduction. * MBIR allows for potential dose reduction in relation to FBP. *
      Visual Grading Regression (VGR) produces direct numerical estimates of potential
      dose reduction. * MBIR strengths 3 and 5 dose reductions were 22-34 and 34-74%. *
      MBIR strength 5 demonstrates inferior performance for liver parenchyma.

PMID- 29368164
TI  - Does a combined CT and MRI protocol enhance the diagnostic efficacy of LI-RADS in
      the categorization of hepatic observations? A prospective comparative study.
AB  - OBJECTIVE: To compare diagnostic performance and agreement between CT, MRI and
      combined CT/MRI in reference to LI-RADS classification system to categorize
      hepatic observations detected in hepatic patients during screening ultrasound.
      METHODS: 240 patients with 296 liver observations detected during ultrasound
      surveillance underwent hepatic CT and MRI examinations, histopathology, and
      clinical and radiological follow-up. Using LI-RADS v2014, six radiologists
      evaluated the observations independently and assigned a LI-RADS category to each
      observation using CT, MRI and combined CT/MRI. RESULTS: Combined CT and MRI in LI
      RADS yielded better accuracy (91.29 %), sensitivity (90.71 %) and specificity
      (92.31 %) for hepatocellular carcinoma (HCC) diagnosis than using MRI or CT
      alone; accuracy, sensitivity and specificity decreased to 85.37 %, 86.34 %, and
      83.65 %, respectively, for MRI and 67.6 %, 54.10 % and 91.35 %, respectively, for
      CT. The intraclass agreement of the LI-RADS scores between CT, MRI and combined
      CT/MRI was excellent (kappa=0.9624 (95 % CI: 0.9318-0.9806)). CONCLUSION: CT and
      MRI are complementary to each other. Combined CT/MRI enabled a more precise
      determination of LI-RADS category of hepatic observations; however, due to the
      expense and minor increase in accuracy, the combined methodology should only be
      utilized in cases of suspected HCC. KEY POINTS: * Hepatic observation may be
      categorized differently depending on the imaging modality used. * We compared LI
      RADS categorization between CT, MRI and combined CT/MRI. * MRI produces higher
      accuracy and sensitivity, while CT produces higher specificity. * Combining CT
      and MRI improves LIRADS categorization reports. * Considering additional cost,
      combined methodology could be restricted to challenging cases.

PMID- 29368165
TI  - Antibiotic resistance in E. coli isolates from patients with urinary tract
      infections presenting to the emergency department.
AB  - PURPOSE: Escherichia coli urine isolates from patients presenting to the
      emergency department at a German tertiary care hospital were retrospectively
      analyzed from January 2015-March 2017 to determine antibiotic resistance patterns
      and patient risk factors for resistance. METHODS: Uncomplicated urinary tract
      infection (UTI) was defined as UTI in the otherwise healthy patient without
      relevant co-morbidities and complications. Patients were assumed to have UTI if
      diagnosis was made by the attending physician with conclusive dipstick results.
      For subgroup analysis, only patients with symptoms suggestive for UTI documented
      in their records were included. RESULTS: 228 patients with a UTI diagnosed by the
      attending physician with E. coli isolated in urine culture were included. 154/228
      patients had documented symptomatic UTI, 57/154 had uncomplicated infection,
      76/154 patients had cystitis, and 124/154 were female. Resistance rates of
      uncomplicated UTI in symptomatic patients were: ciprofloxacin 10.5%,
      cotrimoxazole 15.8%, amoxicillin/clavulanic acid 5.3%, nitrofurantoin 0% (CLSI
      MICs). Previous hospitalization in the last 3 months (including patients living
      in a long-term care facility) was significantly correlated with resistance to
      ciprofloxacin, cotrimoxazole and amoxicillin/clav. Previous hospitalization was a
      strong predictor of resistance to ciprofloxacin and cotrimoxazole in multivariate
      analysis also. Other risk factors correlated with resistance were hematological
      malignancy (for cotrimoxazole) and renal transplantation (for ciprofloxacin).
      CONCLUSIONS: Cotrimoxazole is still an alternative for treating uncomplicated
      cystitis. Previous hospitalization in the last 3 months was a strong predictor of
      resistance to cotrimoxazole and ciprofloxacin. Other risk factors which might
      help guide empirical therapy are hematological malignancy and renal
      transplantation.

PMID- 29368167
TI  - Slow viscoelastic response of resilin.
AB  - The high importance of resilin in invertebrate biomechanics is widely known. It
      is generally assumed to be an almost perfect elastomer in different tissues.
      Whereas mechanical properties of resilin were previously determined mainly in
      tension, here we aimed at studying its mechanical properties in compression.
      Microindentation of resilin from the wing hinge of Locusta migratoria revealed
      the clear viscoelastic response of resilin: about a quarter of the mechanical
      response was assigned to a viscous component in our experiments. Mechanical
      properties were characterized using a generalized Maxwell model with two
      characteristic time constants, poroelasticity theory, and alternatively using a
      1D model with just one characteristic time constant. Slow viscous responses with
      1.7 and 16 s characteristic times were observed during indentation. These results
      demonstrate that the locust flight system is adapted to both fast and slow
      mechanical processes. The fast highly elastic process is related to the flight
      function and the slow viscoelastic process may be related to the wing folding.

PMID- 29368166
TI  - Long-term physical activity leads to a significant increase in serum sRAGE
      levels: a sign of decreased AGE-mediated inflammation due to physical activity?
AB  - There is growing evidence that low levels of the circulating soluble receptor of
      advanced glycation end products (sRAGE) are a valuable predictor of
      cardiovascular disease (CVD). The aim of this prospective study was to
      investigate the influence of long-term physical activity on serum sRAGE levels.
      109 subjects were recruited, and 98 completed the study. Participants were asked
      to perform exercise within the calculated training pulse for 8 months. The
      performance gain was measured/quantified by bicycle stress tests at the beginning
      and end of the observation period. sRAGE was measured at baseline and after 2/6/8
      months by ELISA. Backwards, multiple linear regression analysis was performed to
      investigate the association of co-variables age, sex, BMI, and performance at
      baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI
      and lipoprotein a as significant predictors for baseline sRAGE levels. Compared
      to subjects with a performance gain <= 4.9% subjects with a gain > 5% showed a
      significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate
      negatively with lipoprotein a levels and BMI and long-term physical activity
      leads to a significant increase in serum sRAGE levels (9-22%), whereby the sRAGE
      increase is most pronounced in subjects with initially low-performance levels,
      suggesting that in particular, these subject profit the most from increased
      physical activity. The sport-mediated increase of sRAGE might be a sign of
      decreased AGE-mediated inflammation and highlight the protective effect of sports
      on CVD and other disease which are at least partly mediated by an increased
      inflammation status.Clinical trials registration NCT02097199.

PMID- 29368170
TI  - The Ethics of Discharging Asylum Seekers to Harm: A Case From Australia.
AB  - In February 2016 a twelve-month-old asylum seeker, who came to be know as Baby
      Asha, was transferred from Nauru and hospitalized in Brisbane. This case came to
      public attention after Doctors refused to discharge Asha as she would have been
      returned to detention on Nauru. What in other circumstances would have been
      considered routine clinical care, quickly turned into an act of civil
      disobedience. This paper will discuss the ethical aspects of this case, along
      with its implications for clinicians and the broader healthcare community.

PMID- 29368168
TI  - Biosynthetic and antimicrobial potential of actinobacteria isolated from bulrush
      rhizospheres habitat in Zhalong Wetland, China.
AB  - The wetland ecosystem is known to possess unique vegetation and serves multiple
      functions within the environment. In this study, bacterial bioprospecting of
      bulrush rhizospheres in the Zhalong Wetland, China, was performed using
      comprehensive methods, including strain isolation and phylogenetic analysis, PCR
      detection of biosynthetic gene clusters, assessment of antimicrobial activity,
      metabolite profiling and genome analysis. A total of 27 actinobacterial strains
      were isolated, and their biosynthetic gene clusters (NRPS, PKS-I and PKS-II) were
      investigated; all of the tested strains had at least one of the three
      aforementioned biosynthetic gene clusters. Furthermore, fermentation broth
      extracts produced by these strains showed antimicrobial activities against
      certain pathogens, and ten of the extracts exhibited broad-spectrum antimicrobial
      activity. Liquid chromatography-mass spectrometry (LC-MS) analysis indicated
      chemical diversity of secondary metabolites from these extracts. Among these
      strains, ZLSD-24 generated the largest amounts and types of secondary
      metabolites. Subsequent genome analysis showed that 41 secondary metabolite
      biosynthetic gene clusters were present in the strain ZLSD-24, which was in
      accordance with the LC-MS data. Taken together, the results of this study reveal
      that bulrush rhizosphere habitat in the Zhalong wetland is a promising source of
      novel natural products.

PMID- 29368171
TI  - Truth Disclosure Practices of Physicians in Jordan.
AB  - Disclosure of health information is a sensitive matter, particularly in the
      context of serious illness. In conservative societies-those which predominate in
      the developing world-direct truth disclosure undoubtedly presents an ethical
      conundrum to the modern physician. The aim of this study is to explore the truth
      disclosure practices of physicians in Jordan, a developing country. In this
      descriptive, cross-sectional study, 240 physicians were initially selected by
      stratified random sampling. The sample was drawn from four major hospitals in
      Amman, Jordan. A closed-ended questionnaire was distributed and completed by self
      report. A total of 164 physicians completed the questionnaire. Thirty-seven
      physicians (23 per cent) usually withheld the diagnosis of "serious illness" from
      patients, while 127 physicians (77 per cent) usually divulged the information
      directly. Among the latter, 108 physicians (86 per cent) made exceptions to their
      disclosure policy. Specialists were more likely to withhold health information (p
      = 0.04998). Non-disclosure was primarily motivated by request from the patient's
      family (seventy-one participants, 54 per cent). In twenty cases (15 per cent),
      non-disclosure was undertaken independently. In conclusion, most respondents opt
      to disclose the truth; however, the vast majority of these respondents make
      exceptions. Instances of non-disclosure are primarily motivated by sociocultural
      constructs.

PMID- 29368172
TI  - Engendering Harm: A Critique of Sex Selection For "Family Balancing".
AB  - The most benign rationale for sex selection is deemed to be "family balancing."
      On this view, provided the sex distribution of an existing offspring group is
      "unbalanced," one may legitimately use reproductive technologies to select the
      sex of the next child. I present four novel concerns with granting "family
      balancing" as a justification for sex selection: (a) families or family subsets
      should not be subject to medicalization; (b) sex selection for "family balancing"
      entrenches heteronormativity, inflicting harm in at least three specific ways;
      (c) the logic of affirmative action is appropriated; (d) the moral mandate of
      reproductive autonomy is misused. I conclude that the harms caused by family
      balancing are sufficiently substantive to override any claim arising from a
      supposed right to sex selection as an instantiation of procreative autonomy.

PMID- 29368173
TI  - Changing risk of spring frost damage in grapevines due to climate change? A case
      study in the Swiss Rhone Valley.
AB  - Late spring frost is a severe risk during early plant development. It may cause
      important economic damage to grapevine production. In a warming climate, late
      frost risk either could decline due to the reduction in frost days and an
      advancement of the last day of frost or increase due to a more pronounced shift
      forward of the start of the active growing period of the plants. These
      possibilities were analyzed in a case study for two locations in the lower Swiss
      Rhone Valley (Sion, Aigle) where viticulture is an important part of agriculture.
      Twelve phenology models were calibrated for the developmental stage BBCH09 (bud
      burst) using measured or reconstructed temperature data for two vineyards in
      Changins (1958 to 2012) and Leytron (1977 to 2014) together with observed
      phenological data. The day of year (DOY) for BBCH09 was then modelled for the
      years 1951 to 2050 using the best performing phenology model in combination with
      ten downscaled and bias-corrected climate scenarios. A 100-day period starting
      with BBCH09 was defined, during which daily mean and minimum temperatures were
      used to calculate three frost risk indices in each year. These indices were
      compared between the periods 1961-1990 (reference) and 2021-2050 (climate change
      scenario). Based on the average of the ensemble of climate model chains, BBCH09
      advanced by 9 (range 7-11) (Aigle) and 7 (range 5-8) (Sion) days between the two
      time periods, similar to the shift in the last day of frost. The separate results
      of the different model chains suggest that, in the near future, late spring frost
      risk may increase or decrease, depending on location and climate change
      projections. While for the reference, the risk is larger at the warmer site
      (Sion) compared to that at the cooler site (Aigle), for the period 2021-2050,
      small shifts in both phenology and occurrence of frost (i.e., days with daily
      minimum temperature below 0  degrees C) lead to a small decrease in frost risk at
      the warmer but an increase at the cooler site. However, considerable
      uncertainties remain that are mostly related to climate model chains.
      Consequently, shifts in frost risk remain uncertain for the time period
      considered and the two study locations.

PMID- 29368174
TI  - Impact of Drug-Polymer Miscibility on Enthalpy Relaxation of Irbesartan Amorphous
      Solid Dispersions.
AB  - PURPOSE: Drug-polymer miscibility has been proposed to play a critical role in
      physical stability of amorphous solid dispersions (ASDs). The purpose of the
      current work was to investigate the role of drug-polymer miscibility on molecular
      mobility, measured as enthalpy relaxation (ER) of amorphous irbesartan (IBS) in
      ASDs. METHODS: Two polymers, i.e. polyvinylpyrrolidone K30 (PVP K30) and
      hydroxypropyl methylcellulose acetate succinate (HPMCAS), were used to generate
      ASDs with 10% w/w of the polymer. Drug-polymer miscibility was determined using
      melting point depression (MPD) method. Molecular mobility was assessed from ER
      studies at a common degree of undercooling (DOU) (Tg - 13.0 degrees C +/- 0.5
      degrees C). RESULTS: IBS exhibited higher miscibility in PVP K30 as compared to
      HPMCAS at temperature > 140 degrees C. However, extrapolation of miscibility data
      to storage temperature (62 degrees C) using Flory-Huggins (F-H) theory revealed a
      reversal of the trend. Miscibility of IBS was found to be higher in HPMCAS (2.6%)
      than PVP K30 (1.3%) at 62 degrees C. Stretched relaxation time (taubeta) of
      17.4365 h and 7.0886 h was obtained for IBS-HPMCAS and IBS-PVP K30 ASDs,
      respectively. CONCLUSION: Miscibility of drug-polymer at storage temperature
      explained the behavior of the molecular mobility, while miscibility near the
      melting point provided a reverse trend. Results suggest that drug-polymer
      miscibility determined at temperatures higher than the storage temperature should
      be viewed cautiously.

PMID- 29368175
TI  - Differential Proteomics for Distinguishing Ischemic Stroke from Controls: a Pilot
      Study of the SpecTRA Project.
AB  - A diagnostic blood test for stroke is desirable but will likely require multiple
      proteins rather than a single "troponin." Validating large protein panels
      requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool
      for this task. We compared differences in the abundance of 147 protein markers to
      distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to
      the Emergency Department of one urban hospital within < 24 h from onset) and from
      20 control patients who were enrolled via an outpatient neurology clinic. We
      targeted proteins from the stroke literature plus cardiovascular markers
      previously studied in our lab. One hundred forty-one proteins were quantified
      using MS, 8 were quantified using antibody protein enrichment with MS, and 32
      were measured using ELISA, with some proteins measured by multiple techniques.
      Thirty proteins (4 by ELISA and 26 by the MS techniques) were differentially
      abundant between mimic and stroke after adjusting for age in robust regression
      analyses (FDR < 0.20). A logistic regression model using the first two principal
      components of the proteins significantly improved discrimination between strokes
      and controls compared to a model based on age alone (p < 0.001, cross-validated
      AUC 0.93 vs. 0.78). Significant proteins included markers of inflammation (47%),
      coagulation (40%), atrial fibrillation (7%), neurovascular unit injury (3%), and
      other (3%). These results suggest the potential value of plasma proteins as
      biomarkers for ACVS diagnosis and the role of plasma-based MS in this area.

PMID- 29368176
TI  - Biomechanical performance of the Actifit(r) scaffold is significantly improved by
      selection of irrigation fluid.
AB  - PURPOSE: Clinical reports on meniscal scaffolds seem promising, albeit relatively
      paucity exists regarding their biomechanical behavior. The aim of the study is to
      delineate the impact of differing suture materials and the type as well as the
      temperature of the irrigation fluid on the pull-out strength of a polyurethane
      meniscal scaffold (Actifit(r)). MATERIALS AND METHODS: 128 specimens were
      utilized with horizontal sutures and uniaxial load-to-failure testing was
      performed. We compared two different suture materials-polydioxanone (PDS) and non
      absorbable, braided polyester sutures (NABP)-as well as two common irrigation
      fluids-lactated Ringer's and electrolyte-free, hypotonic Mannitol-Sorbitol. All
      specimens were further evaluated according to two different temperatures [room
      temperature (20  degrees C) and near-core body temperature (37  degrees C)].
      RESULTS: Mean load-to-failure was 53.3 +/- 6.5 N. There was no significant
      difference between the NABP and the PDS group. Ringer group showed a
      significantly higher load-to-failure compared to Purisole (P = .0002). This was
      equivalent for both PDS (P = .0008) and NABP sutures (P = .0008). Significantly
      higher failure loads could be established for the 37 degrees  group (P = .041);
      yet, this difference was neither confirmed for the PDS or in in the NABP
      subgroup. Only the subgroup using Purisole at 37 degrees  showed significantly
      higher failure loads compared to 20 degrees  (P = .017). CONCLUSIONS: This study
      underlines the potential to improve pull-out strength during implantation of an
      Actifit(r) scaffold by alteration of the type of irrigation fluid. Lactated
      Ringer solution provided the highest construct stability in regard to load-to
      failure testing and should be considered whenever implantation of a polyurethane
      meniscal scaffold is conducted.

PMID- 29368177
TI  - Tram system related cycling injuries.
AB  - INTRODUCTION: Understanding of tram-system related cycling injuries (TSRCI) is
      poor. The aim of this study was to report the spectrum of injuries, demographics
      and social deprivation status of patients. Secondary aims included assessment of
      accident circumstances, effects of TSRCI on patients' confidence cycling,
      together with time off work and cycling. METHODS: A retrospective review of
      patients presenting to emergency services across all hospitals in Edinburgh and
      West Lothian with tram related injuries between May 2009 and April 2016 was
      undertaken. Medical records and imagining were analysed and patients were
      contacted by telephone. RESULTS: 191 cyclists (119 males, 72 females) were
      identified. 63 patients sustained one or more fractures or dislocations. Upper
      limb fractures/dislocations occurred in 55, lower limb fractures in 8 and facial
      fractures in 2. Most patients demonstrated low levels of socioeconomic
      deprivation. In 142 cases, the wheel was caught in tram-tracks, while in 32 it
      slid on tracks. The latter occurred more commonly in wet conditions (p = 0.028).
      151 patients answered detailed questionnaires. Ninety-eight were commuting. 112
      patients intended to cross tramlines and 65 accidents occurred at a junction.
      Eighty patients reported traffic pressures contributed to their accident. 120
      stated that their confidence was affected and 24 did not resume cycling. Female
      gender (p < 0.001) and presence of a fracture/dislocation (p = 0.012) were
      independent predictors of negative effects on confidence. Patients sustaining a
      fracture/dislocation spent more time off work (median 5 days vs 1, p < 0.001) and
      cycling (median 57 days vs 21, p < 0.001). CONCLUSIONS: TSRCI occur predominantly
      in young to middle-aged adults with low levels of socioeconomic deprivation, most
      commonly when bicycle wheels get caught in tram-tracks. They result in various
      injuries, frequently affecting the upper limb. Traffic pressures are commonly
      implicated. Most patients report negative effects on confidence and a sizeable
      minority do not resume cycling. TSRCI can result in significant loss of working
      and cycling days.

PMID- 29368178
TI  - Evaluation of accuracy of virtual surgical planning for patient-specific pre
      contoured plate in acetabular fracture fixation.
AB  - BACKGROUND: Acetabular fractures are amongst the most challenging fractures to
      treat because of complex anatomy. Open reduction and internal fixation remains
      the standard treatment for displaced acetabular fractures to achieve anatomical
      reduction as in any other intra-articular fracture. Patient-specific pre
      contoured reconstruction plate template made by a pre-operative virtual surgical
      planning can be useful to respect patient's morphology, reduce surgical
      invasiveness and simplify the surgical procedure. Proper evaluation and surgical
      planning is necessary to achieve these goals. The goal of this study was to
      evaluate the outcomes of using virtual surgical planning and virtually pre
      contoured plate template in comparison with the conventional method of intra
      operative contouring of reconstruction plate for acetabular fracture fixation.
      METHODS: Twenty-five patients were categorized into group A and B by computerized
      randomization. In group A (12 patients), CT-based virtual surgical planning was
      done using Mimics and 3-Matic software to form virtually pre-contoured plates,
      which were 3D printed to act as templates over which 3.5 mm reconstruction plates
      were manually contoured pre-operatively and used for fixation. In group B (13
      patient), conventional method of intra-operative contouring to adapt the plate to
      the fracture region was followed. Blood loss, surgical time, reduction on X-rays
      and post-operative computed tomography were compared between two groups. RESULTS:
      Duration of surgery and total blood loss were found to be less while reduction
      was found to satisfactory/anatomical in higher percentage of Group A than Group B
      patients. CONCLUSIONS: Virtual surgical planning, patient-specific virtually pre
      contoured plate template and 3D printing technology improve the outcomes of
      acetabular fracture surgery by reducing duration and invasiveness of surgery and
      improving the quality of reduction. However, studies with larger sample size are
      required to further validate it.

PMID- 29368179
TI  - Recent Approaches to Improve Medication Adherence in Patients with Coronary Heart
      Disease: Progress Towards a Learning Healthcare System.
AB  - PURPOSE OF REVIEW: Non-adherence to medications for the secondary prevention of
      myocardial infarction (MI) is a major contributor to morbidity and mortality in
      these patients. This review describes recent advances in promoting adherence to
      therapies for coronary artery disease (CAD). RECENT FINDINGS: Two large
      randomized controlled trials to "incentivize" adherence were somewhat
      disappointing; neither financial incentives nor "peer pressure" successfully
      increased rates of adherence in the post-MI population. Patient education and
      provider engagement appear to be critical aspects of improving adherence to CAD
      therapies, where the provider is a physician, pharmacist, or nurse and follow-up
      is performed in person or by telephone. Fixed-dose combinations of CAD
      medications, formulated as a so-called "polypill," have shown some early efficacy
      in increasing adherence. Technological advances that automate monitoring and/or
      encouragement of adherence are promising but seem universally dependent on
      patient engagement. For example, medication reminders via text message perform
      better if patients are required to respond. Multifaceted interventions, in which
      these and other interventions are combined together, appear to be most effective.
      There are several available types of proven interventions through which
      providers, and the health system at large, can advance patient adherence to CAD
      therapies. No single intervention to promote adherence will be successful in all
      patients. Further study of multifaceted interventions and the interactions
      between different interventions will be important to advancing the field. The
      goal is a learning healthcare system in which a network of interventions responds
      and adapts to patients' needs over time.

PMID- 29368180
TI  - [Complications after intramedullary stabilization of clavicle fractures].
AB  - BACKGROUND: Operative treatment of clavicle fractures by intramedullary nailing
      with titanium elastic nailing (TEN) has been established as an alternative to
      plate osteosynthesis for many years. The main complication after TEN
      osteosynthesis is nail migration. The goal of this study was evaluation of
      predictors for medial nail migration and comparison with plate osteosynthesis.
      MATERIAL AND METHODS: A retrospective analysis of electronic patient charts,
      surgical protocols and radiographs of all operatively treated clavicle shaft
      fractures between 2010-2014 (n = 141) was performed. When evaluating the patient
      charts and the surgical protocols special attention was paid to the fracture
      type, the duration of the operation, the need for an open reduction and the onset
      of complications as well as the duration until implant removal. Radiographs were
      analyzed concerning the implant location and an implant migration. RESULTS:
      Surgery time (39 vs. 83 min) as well as the time to implant removal (226 vs. 495
      days) were significantly reduced (p = 0.00), while complication (39% vs. 21.4%)
      as well as reoperation rates (15% vs. 7.1%; p = 0.033) were increased in TEN
      compared to plate osteosynthesis. The main complication was medial nail
      migration. The following predictors regarding medial migration could be
      identified: open or closed reduction (p = 0.021), multifragmentary fractures (p =
      0.049), oblique fractures (p = 0.08) and TEN thickness (33% at 2 mm, 0% at 3 mm).
      DISCUSSION: Advantages of TEN are a shorter surgery time as well as a shorter
      duration until implant removal. The TEN osteosynthesis led to a significantly
      increased complication rate, with nail migration representing the major reason.
      When predictors for medial TEN migration are considered, type B and C fractures
      can also be sufficiently treated by a large diameter TEN.

PMID- 29368181
TI  - Drinking Strategies: Planned Drinking Versus Drinking to Thirst.
AB  - In humans, thirst tends to be alleviated before complete rehydration is achieved.
      When sweating rates are high and ad libitum fluid consumption is not sufficient
      to replace sweat losses, a cumulative loss in body water results. Body mass
      losses of 2% or greater take time to accumulate. Dehydration of >=  2% body mass
      is associated with impaired thermoregulatory function, elevated cardiovascular
      strain and, in many conditions (e.g., warmer, longer, more intense), impaired
      aerobic exercise performance. Circumstances where planned drinking is optimal
      include longer duration activities of >  90 min, particularly in the heat; higher
      intensity exercise with high sweat rates; exercise where performance is a
      concern; and when carbohydrate intake of 1 g/min is desired. Individuals with
      high sweat rates and/or those concerned with exercise performance should
      determine sweat rates under conditions (exercise intensity, pace) and
      environments similar to that anticipated when competing and tailor drinking to
      prevent body mass losses >  2%. Circumstances where drinking to thirst may be
      sufficient include short duration exercise of <  1 h to 90 min; exercise in
      cooler conditions; and lower-intensity exercise. It is recommended to never drink
      so much that weight is gained.

PMID- 29368182
TI  - Administration of Caffeine in Alternate Forms.
AB  - There has been recent interest in the ergogenic effects of caffeine delivered in
      low doses (~ 200 mg or ~ 3 mg/kg body mass) and administered in forms other than
      capsules, coffee and sports drinks, including chewing gum, bars, gels, mouth
      rinses, energy drinks and aerosols. Caffeinated chewing gum is absorbed quicker
      through the buccal mucosa compared with capsule delivery and absorption in the
      gut, although total caffeine absorption over time is not different. Rapid
      absorption may be important in many sporting situations. Caffeinated chewing gum
      improved endurance cycling performance, and there is limited evidence that
      repeated sprint cycling and power production may also be improved. Mouth rinsing
      with caffeine may stimulate nerves with direct links to the brain, in addition to
      caffeine absorption in the mouth. However, caffeine mouth rinsing has not been
      shown to have significant effects on cognitive performance. Delivering caffeine
      with mouth rinsing improved short-duration, high-intensity, repeated sprinting in
      normal and depleted glycogen states, while the majority of the literature
      indicates no ergogenic effect on aerobic exercise performance, and resistance
      exercise has not been adequately studied. Studies with caffeinated energy drinks
      have generally not examined the individual effects of caffeine on performance,
      making conclusions about this form of caffeine delivery impossible. Caffeinated
      aerosol mouth and nasal sprays may stimulate nerves with direct brain connections
      and enter the blood via mucosal and pulmonary absorption, although little support
      exists for caffeine delivered in this manner. Overall, more research is needed
      examining alternate forms of caffeine delivery including direct measures of brain
      activation and entry of caffeine into the blood, as well as more studies
      examining trained athletes and female subjects.

PMID- 29368183
TI  - Vitamin D and the Athlete: Current Perspectives and New Challenges.
AB  - The last decade has seen a dramatic increase in general interest in and research
      into vitamin D, with many athletes now taking vitamin D supplements as part of
      their everyday dietary regimen. The most recognized role of vitamin D is its
      regulation of calcium homeostasis; there is a strong relationship between vitamin
      D and bone health in non-athletic individuals. In contrast, data have
      consistently failed to demonstrate any relationship between serum 25[OH]D and
      bone health, which may in part be due to the osteogenic stimulus of exercise.
      Vitamin D may interact with extra-skeletal tissues such as muscle and the immune
      system to modulate recovery from damaging exercise and infection risk. Given that
      many athletes now engage in supplementation, often consuming extreme doses of
      vitamin D, it is important to assess whether excessive vitamin D can be
      detrimental to health. It has been argued that toxic effects only occur when
      serum 25[OH]D concentrations are greater than 180 nmol.l-1, but data from our
      laboratory have suggested high-dose supplementation could be problematic.
      Finally, there is a paradoxical relationship between serum 25[OH]D concentration,
      ethnicity, and markers of bone health: Black athletes often present with low
      serum 25[OH]D without physiological consequences. One explanation for this could
      be genetic differences in vitamin D binding protein due to ethnicity, resulting
      in greater concentrations of bioavailable (or free) vitamin D in some ethnic
      groups. In the absence of any pathology, screening may be unnecessary and could
      result in incorrect supplementation. Data must now be re-examined, taking into
      consideration bioavailable or "free" vitamin D in ethnically diverse groups to
      enable new thresholds and target concentrations to be established; perhaps, for
      now, it is time to "set vitamin D free".

PMID- 29368184
TI  - Does Cold Water or Ice Slurry Ingestion During Exercise Elicit a Net Body Cooling
      Effect in the Heat?
AB  - Cold water or ice slurry ingestion during exercise seems to be an effective and
      practical means to improve endurance exercise performance in the heat. However,
      transient reductions in sweating appear to decrease the potential for evaporative
      heat loss from the skin by a magnitude that at least negates the additional
      internal heat loss as a cold ingested fluid warms up to equilibrate with body
      temperature; thus explaining equivalent core temperatures during exercise at a
      fixed heat production irrespective of the ingested fluid temperature. Internal
      heat transfer with cold fluid/ice is always 100% efficient; therefore, when a
      decrement occurs in the efficiency that sweat evaporates from the skin surface
      (i.e. sweating efficiency), a net cooling effect should begin to develop. Using
      established relationships between activity, climate and sweating efficiency, the
      boundary conditions beyond which cold ingested fluids are beneficial in terms of
      increasing net heat loss can be calculated. These conditions are warmer and more
      humid for cycling relative to running by virtue of the greater skin surface
      airflow, which promotes evaporation, for a given metabolic heat production and
      thus sweat rate. Within these boundary conditions, athletes should ingest fluids
      at the temperature they find most palatable, which likely varies from athlete to
      athlete, and therefore best maintain hydration status. The cooling benefits of
      cold fluid/ice ingestion during exercise are likely disproportionately greater
      for athletes with physiological disruptions to sweating, such as those with a
      spinal cord injury or burn injuries, as their capacity for skin surface
      evaporative heat loss is much lower; however, more research examining these
      groups is needed.

PMID- 29368185
TI  - Assessing the Role of Muscle Protein Breakdown in Response to Nutrition and
      Exercise in Humans.
AB  - Muscle protein breakdown (MPB) is an important metabolic component of muscle
      remodeling, adaptation to training, and increasing muscle mass. Degradation of
      muscle proteins occurs via the integration of three main systems-autophagy and
      the calpain and ubiquitin-proteasome systems. These systems do not operate
      independently, and the regulation is complex. Complete degradation of a protein
      requires some combination of the systems. Determination of MPB in humans is
      technically challenging, leading to a relative dearth of information. Available
      information on the dynamic response of MPB primarily comes from stable isotopic
      methods with expression and activity measures providing complementary
      information. It seems clear that resistance exercise increases MPB, but not as
      much as the increase in muscle protein synthesis. Both hyperaminoacidemia and
      hyperinsulinemia inhibit the post-exercise response of MPB. Available data do not
      allow a comprehensive examination of the mechanisms behind these responses.
      Practical nutrition recommendations for interventions to suppress MPB following
      exercise are often made. However, it is likely that some degree of increased MPB
      following exercise is an important component for optimal remodeling. At this
      time, it is not possible to determine the impact of nutrition on any individual
      muscle protein. Thus, until we can develop and employ better methods to elucidate
      the role of MPB following exercise and the response to nutrition, recommendations
      to optimize post exercise nutrition should focus on the response of muscle
      protein synthesis. The aim of this review is to provide a comprehensive
      examination of the state of knowledge, including methodological considerations,
      of the response of MPB to exercise and nutrition in humans.

PMID- 29368187
TI  - Lack of pharmacokinetic interaction between fluvastatin and green tea in healthy
      volunteers.
AB  - PURPOSE: The objective of this study is to assess the effects of green tea and
      its major catechin component, (-)-epigallocatechin gallate (EGCG), on CYP2C9
      mediated substrate metabolism in vitro, and the pharmacokinetics of fluvastatin
      in healthy volunteers. METHODS: The metabolism of diclofenac and fluvastatin in
      human recombinant CYP2C9 was investigated in the presence of EGCG. In a
      randomized three-phase crossover study, 11 healthy volunteers ingested a single
      20-mg dose of fluvastatin with green tea extract (GTE), containing 150 mg of
      EGCG, along with water (300 mL), brewed green tea (300 mL), or water (300 mL)
      after overnight fasting. Plasma concentrations of fluvastatin and EGCG were
      measured by ultra-performance liquid chromatography with fluorescence detection
      and a single mass spectrometer. RESULTS: EGCG inhibited diclofenac 4'
      hydroxylation and fluvastatin degradation with IC50 of 2.23 and 48.04 MUM,
      respectively. Brewed green tea used in the clinical study also dose-dependently
      inhibited the metabolism of diclofenac and fluvastatin in vitro. However, no
      significant effects of GTE and brewed green tea were observed in plasma
      concentrations of fluvastatin. The geometric mean ratios with 90% CI for area
      under the plasma concentration-time curve (AUC0-infinity) of fluvastatin were
      0.993 (0.963-1.024, vs. brewed green tea) and 0.977 (0.935-1.020, vs. GTE).
      CONCLUSIONS: Although in vitro studies indicated that EGCG and brewed green tea
      produce significant inhibitory effects on CYP2C9 activity, the concomitant
      administration of green tea and fluvastatin in healthy volunteers did not
      influence the pharmacokinetics of fluvastatin.

PMID- 29368186
TI  - Protection Before Impact: the Potential Neuroprotective Role of Nutritional
      Supplementation in Sports-Related Head Trauma.
AB  - Even in the presence of underreporting, sports-related concussions/mild traumatic
      brain injuries (mTBI) are on the rise. In the absence of proper diagnosis, an
      athlete may return to play prior to full recovery, increasing the risk of second
      impact syndrome or protracted symptoms. Recent evidence has demonstrated that sub
      concussive impacts, those sustained routinely in practice and competition, result
      in a quantifiable pathophysiological response and the accumulation of both
      concussive and sub-concussive impacts sustained over a lifetime of sports
      participation may lead to long-term neurological impairments and an increased
      risk of developing neurodegenerative diseases. The pathophysiological,
      neurometabolic, and neurochemical cascade that initiates subsequent to the injury
      is complex and involves multiple mechanisms. While pharmaceutical treatments may
      target one mechanism, specific nutrients and nutraceuticals have been discovered
      to impact several pathways, presenting a broader approach. Several studies have
      demonstrated the neuroprotective effect of nutritional supplementation in the
      treatment of mTBI. However, given that many concussions go unreported and sub
      concussive impacts result in a pathophysiological response that, too, may
      contribute to long-term brain health, protection prior to impact is warranted.
      This review discusses the current literature regarding the role of nutritional
      supplements that, when provided before mTBI and traumatic brain injury, may
      provide neurological protection.

PMID- 29368188
TI  - The nocebo effect challenges the non-medical infliximab switch in practice.
AB  - BACKGROUND: In clinical practice, non-medical switching of biological medication
      may provoke nocebo effects due to unexplained deterioration of therapeutic
      benefits. Indication extrapolation, idiosyncratic reactions, and
      interchangeability remain challenged in clinical practice after biosimilar
      approval by the European Medicines Agency. The principle of "first do no harm"
      may be challenged in a patient when switching from originator to biosimilar
      biological. AIM: To describe the 1-year results of a pragmatic study on
      infliximab biosimilar implementation in immune-mediated inflammatory disease
      patients on the basis of shared decision-making under effectiveness and safety
      monitoring. METHODS: Inflammatory bowel disease and rheumatology patients on
      infliximab originator were converted to infliximab biosimilar after providing
      informed consent. Nocebo response patients were monitored after switch back to
      originator. Linear mixed models were used to analyze continuous endpoints on
      effectiveness and laboratory outcomes to determine significance (P <= 0.05) of
      change over time after switching. RESULTS: After inviting 146 patients, a group
      of 125 patients enrolled in the project over time, respectively, 73 Crohn's
      disease, 28 ulcerative colitis, nine rheumatoid arthritis, ten psoriatic
      arthritis, and five ankylosing spondylitis patients. No statistically significant
      changes in effectiveness and safety were observed in any of the indications after
      a median of 4 infusions in 9 months of study. An overall nocebo response of 12.8%
      was found among the patients during a minimal observation period of 6 months
      after the transition to biosimilar infliximab. The overall nocebo response rate
      did not differ between the studied indications. CONCLUSIONS: In inflammatory
      bowel disease and rheumatological patients, similar effectiveness and safety were
      demonstrated on the transition into infliximab biosimilar. In our series, patient
      empowerment and registration of treatment outcomes delineated biosimilar
      transition, an approach that hypothetically could reduce nocebo response rates
      which are relevant to account for regarding biosimilar implementation.

PMID- 29368189
TI  - Multi-center prospective survey of inflammatory bowel diseases in Kerala: More
      than 2000 cases.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is considered uncommon in Asia. The
      aim of this study was to document the demographic characteristics and clinical
      aspects of ulcerative colitis (UC) and Crohn's disease (CD) in Kerala, India.
      METHODS: A survey of IBD in Kerala was performed. All gastroenterologists in the
      region were invited. From May 2013 to October 2015, data were collected in a
      standardized pro-forma. RESULTS: Forty-seven doctors in 34 centers contributed
      data. A total of 2142 patients were analyzed. This is the largest state-wide
      survey of IBD in India. Ulcerative colitis was diagnosed in 1112 (38 new),
      Crohn's disease in 980 (53 new), and 50 were unclassified (5 new). The district
      wise distribution of IBD cases correlated with the District-wise Gross State
      Domestic Product (r = 0.69, p < 0.01). Three percent was below the age of 18.
      Patients with UC had more diarrhea (73% vs. 51%), bleeding PR (79% vs. 34%), and
      intermittent flares (35% vs. 13%) (all p < 0.01). Patients with CD had more
      abdominal pain (62% vs. 46%), weight loss (53% vs. 40%), fever (28% vs. 18%), and
      history of antituberculosis treatment (21% vs. 5%) (all p < 0.01). Compared to
      adults, children (below 18 years) were more likely to have extensive UC (58% vs.
      34%, p < 0.01) and unclassified IBD (15% vs. 2%, p < 0.01). CONCLUSION:
      Inflammatory bowel disease is common in Kerala, India. The disease
      characteristics of patients with IBD are almost similar to those from other parts
      of the country. Both UC and CD were seen in equal proportion in Kerala.

PMID- 29368190
TI  - Use of self-expanding metal stents for difficult variceal bleed.
AB  - BACKGROUND/AIM: Patients with variceal band ligation (VBL)-induced ulcer bleeding
      and those with persisting bleeding in spite of VBL carry a high mortality.
      Balloon tamponade and transjugular intrahepatic portosystemic shunt have
      limitations in terms of complications, cost, and availability. The aim was to
      evaluate the efficacy of Sx-Ella Danis stent in persistent or complicated
      variceal bleeding. METHODS: Twelve patients with either persistent variceal
      bleeding or VBL-induced ulcer bleeding were treated with the placement of Sx-Ella
      Danis stents. The patients were followed up for mortality, complications, and
      efficacy to control bleeding. RESULTS: Stents were inserted successfully in all
      12 patients (with immediate hemostasis). There was an immediate cessation of
      bleeding in all 12 patients with no stent-related complication. Five out of 12
      patients died during 30 days post-procedure due to worsening encephalopathy or
      sepsis. Enteral feeding could be started in all 12 patients 6 h after stent
      placement. One patient had bleeding 10 days after stent removal and was re
      stented but expired 7 days later. Stents were removed in eight patients at a mean
      duration of 17.5 days. (range 7 to 30 days). CONCLUSIONS: Sx-Ella Danis stent is
      a useful modality to control persistent variceal bleeding as well VBL-related
      ulcer bleeding.

PMID- 29368191
TI  - Exploring current status of Helicobacter pylori infection in different age groups
      of patients with dyspepsia.
AB  - Recent data from Asian countries including India has shown a significant decline
      in the frequency of peptic ulcer disease (PUD) compared to the past. H. pylori is
      considered the most important risk factor for PUD, and we aimed to explore the
      current frequency of H. pylori infection in different age groups of patients with
      dyspepsia. Patients >15 years of age with dyspeptic symptoms were prospectively
      recruited in this study from 2010 to 2014 after obtaining informed consent.
      Patients were divided into three age groups: 15-30 years, 31-50 years, and >50
      years, and the minimum sample size required in the three groups with a power of
      90% was 259, 256, and 188, respectively. All patients underwent upper
      gastrointestinal endoscopy; rapid urease test was done on gastric mucosal biopsy
      to detect H. pylori. The clinical, demographic features and socioeconomic status
      were recorded. The institute review board approved the study. We included 1000
      patients with dyspepsia during the study period. Their mean age was 40.0+13.3
      years, and 69.3% were males. Infection with H. pylori was detected in 419 (41.9%)
      patients. Among men, H. pylori was present in 45.7% while the frequency of
      infection in women was lower at 33.2% (p < 0.001). In the 15-30 years age group
      (n = 303), the frequency of infection was 42.6% while it was 48.3% in the 31-50
      years group (n = 350) and 34.9% in the above 50 years group (n = 347). Male sex
      was a significant risk factor for H. pylori infection (p < 0.001). H. pylori
      infection, an important risk factor for PUD, was detected in less than half of
      the dyspeptic patients in the current study.

PMID- 29368192
TI  - Cirrhotic cardiomyopathy is less prevalent in patients with Budd-Chiari syndrome
      than cirrhosis of liver.
AB  - BACKGROUND AND AIM: Cirrhotic cardiomyopathy (CCM) is associated with high
      mortality after transjugular intrahepatic portosystemic shunt (TIPS) and liver
      transplantation in patients with cirrhosis. There is no data about the prevalence
      or impact of CCM in Budd-Chiari syndrome (BCS). We assessed the prevalence of CCM
      in patients with BCS and its impact on outcome after radiological intervention.
      METHODS: Thirty-three consecutive patients with BCS (15 men) and 33 controls with
      hepatitis B-related cirrhosis (18 men, matched for Child-Pugh score) were
      evaluated with baseline electrocardiography (ECG), echocardiography (ECHO) and
      dobutamine stress ECHO, and ECG (DSE). The two groups were compared for
      prevalence of CCM. Patients with BCS with and without CCM were assessed for
      development of heart failure, duration of intensive care unit (ICU) stay, and in
      hospital mortality immediately after radiological intervention. RESULTS: Fewer
      patients with BCS had CCM (7/21 vs. 21/33; p = 0.001, OR-0.16, CI [0.05-0.5]),
      diastolic dysfunction (DD) (0/33 vs. 6/33; p = 0.01, OR-0.06, CI [0.00-1.1]), and
      prolonged QTc interval (5/33 vs.17/33; p = 0.001, OR-0.16, CI [0.05-0.5]) despite
      correction for age. Patients with BCS had lower end-systolic and end-diastolic
      volumes of left and right ventricles. None of the 19 patients (five with CCM)
      with BCS undergoing radiological intervention (12 TIPS, 4 inferior vena cava, and
      3 hepatic vein stenting) developed heart failure or had prolonged ICU stay. There
      was no in-hospital mortality. CONCLUSION: Patients with BCS have lower frequency
      of CCM as compared to patients with cirrhosis. CCM may not adversely affect
      outcomes after radiological interventions.

PMID- 29368193
TI  - Periprocedural Anticoagulation Management for Atrial Fibrillation Ablation:
      Current Knowledge and Future Directions.
AB  - Catheter ablation (CA) for atrial fibrillation (AF) is an established first-line
      approach to the management of drug-refractory AF. Although, advancements in
      procedural techniques and technology have improved the efficacy and safety of CA,
      thromboembolism (TE) remains one of the most feared periprocedural complications.
      Minimizing the risk of TE during and after CA requires a multifaceted approach,
      in which periprocedural anticoagulation plays a central role. The goal of
      anticoagulation before, during, and after CA is to minimize TE risk without
      excessively increasing the risk of adverse bleeding. Generally, there are two
      broad approaches to periprocedural anticoagulation management, "interrupted" or
      "uninterrupted." Interrupted refers to those patients in whom their oral
      anticoagulant is stopped before the CA, with or without "bridging" with another
      anticoagulant, while uninterrupted refers to continuation of oral anticoagulation
      throughout the periprocedural period. The strongest evidence supports an
      uninterrupted oral anticoagulation strategy with warfarin, which is currently the
      standard of care. The introduction of the novel anticoagulants has added some
      complexity to the decision making. Current data generally supports that these are
      safe to use and are not associated with any additional procedural risk or adverse
      events (thromboembolism or bleeding) compared to warfarin. At present, based upon
      current evidence from randomized trials, dabigatran and rivaroxaban are
      reasonable alternatives to warfarin for an uninterrupted approach, while further
      data is needed (and trials are ongoing) for apixaban and edoxaban. In this
      article, we discuss the different approaches to the management of periprocedural
      anticoagulation and the data supporting their use.

PMID- 29368194
TI  - The impact of parity on life course blood pressure trajectories: the HUNT study
      in Norway.
AB  - The drop in blood pressure during pregnancy may persist postpartum, but the
      impact of pregnancy on blood pressure across the life course is not known. In
      this study we examined blood pressure trajectories for women in the years
      preceding and following pregnancy and compared life course trajectories of blood
      pressure for parous and nulliparous women. We linked information on all women who
      participated in the population-based, longitudinal HUNT Study, Norway with
      pregnancy information from the Medical Birth Registry of Norway. A total of
      23,438 women were included with up to 3 blood pressure measurements per woman.
      Blood pressure trajectories were compared using a mixed effects linear spline
      model. Before first pregnancy, women who later gave birth had similar mean blood
      pressure to women who never gave birth. Women who delivered experienced a drop
      after their first birth of - 3.32 mmHg (95% CI, - 3.93, - 2.71) and - 1.98 mmHg
      (95% CI, - 2.43, - 1.53) in systolic and diastolic blood pressure, respectively.
      Subsequent pregnancies were associated with smaller reductions. These pregnancy
      related reductions in blood pressure led to persistent differences in mean blood
      pressure, and at age 50, parous women still had lower systolic (- 1.93 mmHg; 95%
      CI, - 3.33, - 0.53) and diastolic (- 1.36 mmHg; 95% CI, - 2.26, - 0.46) blood
      pressure compared to nulliparous women. The findings suggest that the first
      pregnancy and, to a lesser extent, successive pregnancies are associated with
      lasting and clinically relevant reductions in systolic and diastolic blood
      pressure.

PMID- 29368195
TI  - Advanced treatment of petrochemical wastewater by combined ozonation and
      biological aerated filter.
AB  - The secondary effluent from a petrochemical wastewater treatment plant was
      treated by biological aerated filter (BAF) before and after ozonation, namely
      BAF1 and BAF2, respectively. The results showed that BAF2 fed with the ozonized
      secondary effluent exhibited a high efficiency in degrading organic pollutants.
      The removal efficiency of COD and NH4-N was 6.0 +/- 3.2 and 48.2~18.6% for BAF1
      and 12.5 +/- 5.8 and 62.1~40.9% for BAF2, respectively, during the whole
      operation. The integration system of ozonation and BAF could tolerate a higher
      organic loading rate. When HRT decreased from 4 to 1 h, COD removal efficiency
      decreased from 12 to 4% for the BAF1 system, but it kept almost unchanged at high
      levels of 27-32% for the ozonation-BAF2 system, with around 20% removal by
      ozonation. The biomass in BAF2 exhibited a higher activity of protease, DHA, and
      SOUR than that in BAF1. The organic pollutants in influent and effluent of BAF
      were mainly ester compounds, which were difficult to biodegrade by BAF. The
      predominant genera in BAF1 were Gemmatimonadaceae uncultured, Thauera, and
      Thiobacillus, while the dominant genera in BAF2 were Nitrospira,
      Gemmatimonadaceae uncultured, and Flexibacter, respectively. Overall, BAF2
      performed better than BAF1 in organic pollutant removal and microbial activity.
      The ozonation process was vital for BAF to treat petrochemical secondary
      effluent.

PMID- 29368196
TI  - An assessment of emergy, energy, and cost-benefits of grain production over 6
      years following a biochar amendment in a rice paddy from China.
AB  - Biochar soil amendment had been increasingly advocated for improving crop
      productivity and reducing carbon footprint in agriculture worldwide. However, the
      long-term benefits of biochar application with farming systems had not been
      thoroughly understood. This study quantified and assessed emergy, energy, and
      economic benefits of rice and wheat production throughout 6 rotation years
      following a single biochar amendment in a rice paddy from Southeastern China.
      Using the data from farm inventory, the quantified emergy indices included grain
      outputs, unit emergy value, and relative percentage of free renewable resources,
      environmental loading ratio, emergy yield ratio, and emergy sustainability index
      (ESI). The results indicated contrasting differences in these emergy values
      between biochar-amended and unamended production systems over the 6 years. The
      overall emergy efficiency of rice and wheat productions in biochar-amended system
      were higher by 11-28 and 15-47%, respectively, than that of unamended one of
      which the production being highly resource intensive. Moreover, ESI on average
      was 0.46 for rice and 0.63 for wheat in amended system, compared to 0.35 for rice
      and 0.39 for wheat in unamended one. Furthermore, over the 6 years following a
      single application, the ESI values showed considerable variation in the unamended
      system but consistently increasing in the amended system. Again, the biochar
      amended system exerted significantly higher energy and economic return than the
      unamended one. Nonetheless, there was a tradeoff between rice and wheat in grain
      yield and net economic gain. Overall, biochar amendment could be a viable measure
      to improve the resilience of grain production while to reduce resource intensity
      and environment impacts in paddy soil from China.

PMID- 29368197
TI  - Plasmas ozone inactivation of Legionella in deionized water and wastewater.
AB  - The results show that ozone concentration determination using ultraviolet
      spectrophotometry (UV-2450) at 258 nm is easier than using indigo method at 600
      nm. A strong linear relationship was found between purge time and O3
      concentration in deionized water. Ozone concentration can be predicted in
      deionized water. A higher O3 flow rate or lower temperature led to a higher O3
      concentration. Ozone concentration was stable in 60 min, so that ozone self
      decomposition could be ignored at ozone concentrations below 0.4 mg L-1. A higher
      temperature led to a higher inactivation efficiency and rate, and that a lower
      temperature led to a lower ozone decay rate and inactivation efficiency even if
      ozone solubility increased when temperature decreased. The fastest inactivation
      rate occurred before c0t = 165 MUg L-1 s, but the inactivation rate decreased
      after c0t = 165 MUg L-1 s with tail phenomena. The tail phenomena were clearly
      observed and may be caused by oxidization of lipopolysaccharides (LPS), cell
      membrane, etc. The activation energy Ea = 55,404 +/- 0.3 J mol-1 were obtained
      for Legionella inactivation with ozone in deionized water. Ozone maximum decay
      rate was positively proportional to COD concentration. COD impacted on ozone
      concentration seriously. Higher COD concentration resulted in higher ozone decay
      rate. COD could result in ozone concentration decrement rapidly to a steady value
      in 5 s. Higher initial ozone concentration resulted in higher germ inactivation
      rate. Higher initial COD concentration resulted in lower Legionella inactivation
      efficiency. COD was easier to react with ozone than Legionella. The relationship
      among the initial COD concentrations COD0, the initial O3 concentration c0, and
      the O3 contact time t necessary for a 99.999% reduction of Legionella in
      wastewater can be expressed in some equations. O3 disinfection time t necessary
      for a 99.999% reduction of Legionella can be predicted by Eqs. (10) and (11).
      Graphical abstract ?.

PMID- 29368198
TI  - Trace metal occurrence in Mediterranean seaweeds.
AB  - Seaweeds have been used as animal feed since a long time and are consumed as food
      in several cultures. In fact, macroalgae are a source of protein, fiber,
      polyunsaturated fat, and minerals. The concentration of trace elements was
      determined in dominant macroalga species from three sites of the northwestern
      Mediterranean Sea. A high interspecies variability was observed, with higher
      metal levels in brown and green than those in red seaweeds. The maximum values
      set by European regulations for arsenic, mercury, and cadmium in food and feed
      were never exceeded, but a few samples were very close to limits set for mercury.
      Conversely, the maximum limit for lead in feed was exceeded in all species from
      one of the considered sites. Analogously, lead in seaweeds could constitute a
      potential risk for human health, due to the exceeding of the maximum value set
      for food supplements.

PMID- 29368199
TI  - Studies on biogas-fuelled compression ignition engine under dual fuel mode.
AB  - Experimental investigation has been carried out to utilize biogas as an
      alternative source of energy in compression ignition (CI) engine under dual fuel
      operational mode. Biogas was inducted into the inlet manifold at different flow
      rates along with fresh air through inlet manifold and diesel was injected as a
      pilot fuel to initiate combustion under dual fuel mode. The engine performance
      and emission characteristics of dual fuel operational mode were analyzed at
      different biogas flow rates and compared with baseline conventional diesel fuel.
      Based upon the improved performance and lower emission characteristics under the
      dual fuel operation, the optimum flow rate of biogas was observed to be 2.2 kg/h.
      The lower brake thermal efficiency (BTE) and higher brake-specific energy
      consumption (BSEC) were noticed with biogas-diesel fuel under dual fuel mode when
      compared with neat diesel operation. Test results showed reduced NO x emissions
      and smoke opacity level in the exhaust tailpipe emissions. However, higher
      hydrocarbon (HC) and carbon monoxide (CO) emissions were noticed under dual fuel
      mode at entire engine loads when compared with baseline fossil petro-diesel.
      Hence, the use of low-cost gaseous fuel such as biogas would be an economically
      viable proposition to address the current and future problems of energy scarcity
      and associated environmental concerns.

PMID- 29368200
TI  - Use of statistical analysis to validate ecogenotoxicology findings arising from
      various comet assay components.
AB  - Cirrhinus mrigala, Labeo rohita, and Catla catla are economically important fish
      for human consumption in Pakistan, but industrial and sewage pollution has
      drastically reduced their population in the River Chenab. Statistics are an
      important tool to analyze and interpret comet assay results. The specific aims of
      the study were to determine the DNA damage in Cirrhinus mrigala, Labeo rohita,
      and Catla catla due to chemical pollution and to assess the validity of
      statistical analyses to determine the viability of the comet assay for a possible
      use with these freshwater fish species as a good indicator of pollution load and
      habitat degradation. Comet assay results indicated a significant (P < 0.05)
      degree of DNA fragmentation in Cirrhinus mrigala followed by Labeo rohita and
      Catla catla in respect to comet head diameter, comet tail length, and % DNA
      damage. Regression analysis and correlation matrices conducted among the
      parameters of the comet assay affirmed the precision and the legitimacy of the
      results. The present study, therefore, strongly recommends that genotoxicological
      studies conduct appropriate analysis of the various components of comet assays to
      offer better interpretation of the assay data.

PMID- 29368201
TI  - Fraction distribution and leaching behavior of heavy metals in dredged sediment
      disposal sites around Meiliang Bay, Lake Taihu (China).
AB  - The objectives of this study were to characterize the heavy metal contamination
      status of surface soils sampled at two dredged sediment land disposal sites (the
      Baimao and Kongwan landfills) in Meiliang Bay, Lake Taihu, China, as well as to
      investigate the effect on their leaching behaviors due to acid rain. Among all
      the metals, only the nickel content in the Baimao landfill was higher than the
      Chinese reference value, and all metal contents were below the limit values for
      agricultural soils. The fraction distribution of metals by sequential extraction
      was similar at both sites. Cadmium had a relatively high proportion of
      exchangeable-carbonate fractions, while the other metals were mainly classified
      as residue fractions. The metals released from soils by simulated rainwater
      comprised less than 1% of the total soil metal content, and the effect of acid
      rain on heavy metal release from dredged sediments in land disposal sites was
      found to be negligible at both sites. All results indicate no environmental
      concern for the land disposal of dredged sediments and support the feasibility of
      beneficially reusing dredged sediment soils as a supplement to agricultural
      soils.

PMID- 29368202
TI  - Differential distribution of metals in tree tissues growing on reclaimed coal
      mine overburden dumps, Jharia coal field (India).
AB  - Opencast bituminous coal mining invariably generates huge amount of metal
      polluted waste rocks (stored as overburden (OB) dumps) and reclaimed by planting
      fast growing hardy tree species which accumulate metals in their tissues. In the
      present study, reclaimed OB dumps located in Jharia coal field (Jharkhand, India)
      were selected to assess the accumulation of selected metals (Pb, Zn, Mn, Cu and
      Co) in tissues (leaf, stem bark, stem wood, root bark and root wood) of two
      commonly planted tree species (Acacia auriculiformis A.Cunn. ex Benth. and Melia
      azedarach L.). In reclaimed mine soil (RMS), the concentrations of pseudo-total
      and available metals (DTPA-extractable) were found 182-498 and 196-1877% higher,
      respectively, than control soil (CS). The positive Spearman's correlation
      coefficients between pseudo-total concentration of Pb and Cu (r = 0.717; p <
      0.05), Pb and Co (r = 0.650; p < 0.05), Zn and Mn (0.359), Cu and Co (r = 0.896;
      p < 0.01) suggested similar sources for Pb-Cu-Co and Mn-Zn. Among the five tree
      tissues considered, Pb selectively accumulated in root bark, stem bark and
      leaves; Zn and Mn in leaves; and Cu in root wood and stem wood. These results
      suggested metal accumulation to be "tissue-specific". The biological indices
      (BCF, TFleaf, TFstem bark and TFstem wood) indicated variation in metal uptake
      potential of different tree tissues. The study indicated that A. auriculiformis
      could be employed for Mn phytoextraction (BCF, TFleaf, TFstem bark and TFstem
      wood > 1). The applicability of both the trees in Cu phytostabilization (BCF > 1;
      TFleaf, TFstem bark and TFstem wood < 1) was suggested. The study enhanced
      knowledge about the selection of tree species for the phytoremediation of coal
      mine OB dumps and specific tree tissues for monitoring metal pollution.

PMID- 29368203
TI  - Enhanced removal performance of Cr(VI) by the core-shell zeolites/layered double
      hydroxides (LDHs) synthesized from different metal compounds in constructed rapid
      infiltration systems.
AB  - Nine kinds of LDHs were synthesized by the co-precipitation method under alkaline
      conditions with different combinations of trivalent metal compounds (FeCl3,
      AlCl3, CoCl3) and divalent metal compounds (CaCl2, MgCl2, ZnCl2), which were then
      coated in situ on the surface of zeolites to synthesize core-shell zeolites/LDHs
      composites. The zeolites before and after modification were characterized by SEM
      and X-ray fluorescence spectrometry. Using the different core-shell zeolites/LDHs
      and original zeolite substrates, the constructed rapid infiltration systems
      (CRIS) simulated test columns were set to treat the municipal sewage containing
      hexavalent chromium, Cr(VI). Isothermal adsorption tests were subsequently
      performed. The average removal efficiencies of the small-sized zeolites were much
      higher than those of the large-sized zeolites. For the small-sized zeolites, the
      Cr(VI) removal performances of the Mg-LDHs- and Al-LDHs-modified zeolite
      substrates were efficiently enhanced in particular, which could reach over 90%.
      And the removal rate of core-shell zeolites/ZnAl-LDHs reached 94.5%. Meanwhile,
      the maximum adsorption capacity of ZnAl-LDHs-modified zeolites could reach 51.0
      mg/kg, indicating that the adsorption properties could be enhanced by ZnAl-LDHs
      coating. During the purification experiments, most of the LDHs-modified zeolites
      maintained their predominant chemical adsorption ability for the removal of
      Cr(VI). Therefore, the small-sized core-shell zeolites/ZnAl-LDHs composites could
      be used as potential substrates for the efficient removal of Cr(VI) in CRIS.

PMID- 29368204
TI  - A synergetic biomineralization strategy for immobilizing strontium during
      calcification of the coccolithophore Emiliania huxleyi.
AB  - The coccolithophore species Emiliania huxleyi has one of the most global
      distributions in the modern oceans. They are characteristically covered with
      calcite scales called coccoliths. In this study, stable strontium immobilization
      during the calcification process was investigated to indirectly assess a proposed
      bioremediation approach for removing Sr2+ contamination from marine environments.
      Results indicate that E. huxleyi has high Sr2+ tolerance and removal efficiency
      in response to Sr2+ stress ranging from 5.6 to 105.6 ppm. Sr2+ immobilization
      during E. huxleyi calcification indicates a concentration-dependent synergistic
      mechanism. At lower concentrations of Sr2+ (25.6 ppm), Sr2+ is incorporated into
      coccoliths through competitive supply between Sr2+ and Ca2+. In addition, calcite
      productivity decreases with increased Sr2+ removal efficiency due to
      crystallographic transformation of coccoliths from hydrated calcite into
      aragonite at 55.6 ppm Sr2+. Further formation of strontianite at 105.6 ppm Sr2+
      is due to precipitation of Sr2+ on the edge of the rims and radial arrays of the
      coccoliths. Our study implies that coccolithophores are capable of significant
      removal of Sr2+ from the marine environment.

PMID- 29368206
TI  - Erratum to: Differential expression of two class III chitinases in two types of
      roots of Quercus robur during pre-mycorrhizal interactions with Piloderma
      croceum.

PMID- 29368205
TI  - Antipsychotic drugs for patients with schizophrenia and predominant or prominent
      negative symptoms: a systematic review and meta-analysis.
AB  - BACKGROUND: Negative symptoms are the core of schizophrenia, but whether
      antipsychotics are efficacious for their treatment is unclear. Moreover, there is
      debate whether patients in relevant trials should have predominant negative
      symptoms or whether prominent negative symptoms are also acceptable. METHODS: We
      systematically reviewed randomised, blinded antipsychotic drug trials in patients
      with schizophrenia and either predominant or prominent negative symptoms (last
      search Dec 12, 2017). Separate pairwise meta-analyses were conducted in these two
      populations. The primary outcome was negative symptoms. Depressive, symptoms,
      positive symptoms, and extrapyramidal side-effects were analysed as causes of
      secondary negative symptoms. FINDINGS: We included 21 randomized-controlled
      trials with 3451 participants which revealed the following significant
      differences in the primary outcome: in patients with predominant negative
      symptoms amisulpride was superior to placebo (N = 4; n = 590, SMD 0.47, CI 0.23,
      0.71), olanzapine was superior to haloperidol in a small trial (n = 35) and
      cariprazine outperformed risperidone (N = 1, n = 456, SMD - 0.29, CI - 0.48, -
      0.11). In patients with prominent negative symptoms, olanzapine and quetiapine
      were superior to risperidone in single trials. Overall, studies in prominent
      negative symptoms were potentially more confounded by improvements of secondary
      negative symptoms. INTERPRETATION: Amisulpride is the only antipsychotic that
      outperformed placebo in the treatment of predominant negative symptoms, but there
      was a parallel reduction of depression. Cariprazine was better than risperidone
      in a large trial that was well-controlled for secondary negative symptoms, but
      the trial was sponsored by its manufacturer. Future trials should apply
      scientifically developed definitions such as the deficit syndrome and the
      persistent negative symptoms concept.

PMID- 29368207
TI  - Cognitive and Interpersonal Vulnerabilities to Adolescent Depression:
      Classification of Risk Profiles for a Personalized Prevention Approach.
AB  - Despite interest in psychosocial vulnerabilities to depression, little is known
      about reliable and valid individualized risk profiles that can be used to match
      individuals to evidence-based interventions for depression. This study
      investigated well-established cognitive and interpersonal vulnerabilities to
      depression among youth to discern an evidence-based risk classification approach
      which is being used in a personalized depression prevention randomized clinical
      trial. Data were drawn from a general community sample of adolescents (N = 467;
      ages 10-16, mean 13.14, SD = 1.62; 57% females) who were followed prospectively
      for 3 years. Youth completed measures of cognitive (negative cognitive style,
      dysfunctional attitudes, rumination) and interpersonal (support and conflict with
      peers and parents, excessive reassurance seeking, social competence, co
      rumination) risks to depression, and then were followed longitudinally for onset
      of depression. Principal axis factor analyses showed that three latent factors-
      cognitive vulnerability, interpersonal support, and interpersonal conflict-
      optimally represented the structure of these risk factors. Clinically practical
      and meaningful cutoffs, based on tertile cut-off scores on cognitive and
      interpersonal risk measures, were used to categorize youth into relatively
      balanced high and low cognitive and interpersonal risk groups. These risk
      classification groups exhibited validity (AUC > 0.70) by predicting prospective
      onsets of depressive episodes at 18-months follow-ups. These findings demonstrate
      a reliable and valid approach to synthesize psychosocial vulnerabilities to
      depression, specifically cognitive and interpersonal risks. Results are discussed
      in terms of using these risk classifications profiles to test personalized
      prevention of depression during adolescence.

PMID- 29368208
TI  - Comparison of brain activity between motor imagery and mental rotation of the
      hand tasks: a functional magnetic resonance imaging study.
AB  - Motor imagery (MI) has been considered effective in learning and practicing
      movements in many fields. However, when evaluating the effectiveness of this
      technique, the examiner has no way of assessing the participant's motor imagery
      process. As an alternative, we have been exploring a mental body-part rotation
      task, in which the examiner can estimate the participant's motivation and ability
      to sustain attention through the scored results. In this study, we aimed to
      investigate the possible application of a mental rotation (MRot) task and used
      fMRI to compare the brain activity during the MRot task with that during an MI
      task in healthy volunteers. Increased blood oxygenation level-dependent signals
      were observed bilaterally in the premotor areas and supplementary motor area
      during performance of both MI and MRot tasks. Our findings suggest that MRot
      could be an alternative to MI.

PMID- 29368209
TI  - Breast cancer risk associated with genes encoding DNA repair MRN complex: a study
      from Punjab, Pakistan.
AB  - BACKGROUND: Variants of DNA repair genes are extensively reported to cause
      genetic instability and increase the risk of breast cancer. In combination with
      NBS1, MRE11 and RAD50 constitute an MRN (MRE11-RAD50-NBS1) complex that repairs
      DNA damage. However, certain genetic alterations in MRE11 and RAD50 produce
      abnormal protein that affects the repairing process and may result in malignancy.
      We aimed to investigate the association of MRE11 and RAD50 polymorphisms with
      breast risk in the female population of Punjab, Pakistan. METHODS: We collected
      blood samples of 100 breast cancer patients and 100 tumor-free females selected
      as controls. Extracted DNA was genotyped by tetra ARMS-PCR followed by gel
      electrophoresis. Results were analyzed by SPSS and SNPstats to analyze the
      association of different clinical factors and SNPs (single nucleotide
      polymorphisms) with the risk of breast cancer. RESULTS: We found that the
      increased risk of breast cancer is associated with MRE11 variant rs684507 (odds
      ratio-OR 3.71, 95% confidence interval-CI 1.68-8.18, p value < 0.0001), whereas,
      RAD50 variant rs28903089 appeared to have protective effect (OR 0.55, CI 0.29
      1.02, p value = 0.003). Additionally, clinical factors such as positive family
      history, life style, and marital status also play significant roles in breast
      cancer development. CONCLUSION: In the present study, strong risk of breast
      cancer was associated with MRE11 gene. However, RAD50 showed protective effect.
      Additionally, clinical factors are also pivotal in risk assessment. We anticipate
      that targeting specific genetic variations confined to ethnic groups would be
      more effective in future therapeutic approaches for prevention and treatment of
      breast cancer.

PMID- 29368210
TI  - Foot posture in female patients 5 years after breast-conserving surgery: a case
      control study.
AB  - PURPOSE: Along with the improvement in the outcomes of breast cancer treatment
      being observed in the recent years, long-term studies to assess distant adverse
      effects of the treatment have become increasingly important. The objective of
      this study was to assess the foot posture in patients subjected to breast
      conserving therapy. The assessment was made 5 years after the surgical procedure.
      METHODS: 116 female patients (mean age of 58.75 years) were qualified into a case
      control study. Foot posture on the operated breast side (F1) as well as on the
      contralateral side (F2) was evaluated using a computer-based foot analysis tool
      as an extension of projection moire-based podoscopic examination. Comparisons
      were made for the following parameters: limb load, L-foot length, W-foot width,
      L/W-Wejsflog index, ALPHA-hallux valgus angle, BETA-little toe varus angle, GAMMA
      heel angle, KY-Sztriter-Godunov index, CL-Clarke's angle, HW-heel width. RESULTS:
      Five years after BCT, patients placed higher load on the foot on the side of the
      healthy breast (p = 0.0011). No statistically significant differences were
      observed between F1 and F2 with respect to other foot posture parameters (p >
      0.05). No statistically significant differences were observed in foot posture
      parameters in patients having undergone BCT + ALND (axillary lymph node
      dissection) procedure as compared to patients subjected to BCT + SLNB (sentinel
      lymph node biopsy) procedure (p > 0.05). CONCLUSIONS: No changes in foot posture
      were observed in patients 5 years after the BCT procedure. The type of the
      surgical procedure related to the lymph nodes within the axillary fossa has no
      effect on changes in foot posture.

PMID- 29368211
TI  - Validation of a Model Predicting Anti-infective Lung Penetration in the
      Epithelial Lining Fluid of Humans.

PMID- 29368213
TI  - Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid
      barrier in health and disease.
AB  - The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is
      located at the choroid plexuses. At the interface between two circulating fluids,
      these richly vascularized veil-like structures display a peculiar morphology
      explained by their developmental origin, and fulfill several functions essential
      for CNS homeostasis. They form a neuroprotective barrier preventing the
      accumulation of noxious compounds into the CSF and brain, and secrete CSF, which
      participates in the maintenance of a stable CNS internal environment. The CSF
      circulation plays an important role in volume transmission within the developing
      and adult brain, and CSF compartments are key to the immune surveillance of the
      CNS. In these contexts, the choroid plexuses are an important source of
      biologically active molecules involved in brain development, stem cell
      proliferation and differentiation, and brain repair. By sensing both
      physiological changes in brain homeostasis and peripheral or central insults such
      as inflammation, they also act as sentinels for the CNS. Finally, their role in
      the control of immune cell traffic between the blood and the CSF confers on the
      choroid plexuses a function in neuroimmune regulation and implicates them in
      neuroinflammation. The choroid plexuses, therefore, deserve more attention while
      investigating the pathophysiology of CNS diseases and related comorbidities.

PMID- 29368212
TI  - The DNA methylome of DDR genes and benefit from RT or TMZ in IDH mutant low-grade
      glioma treated in EORTC 22033.
AB  - The optimal treatment for patients with low-grade glioma (LGG) WHO grade II
      remains controversial. Overall survival ranges from 2 to over 15 years depending
      on molecular and clinical factors. Hence, risk-adjusted treatments are required
      for optimizing outcome and quality of life. We aim at identifying mechanisms and
      associated molecular markers predictive for benefit from radiotherapy (RT) or
      temozolomide (TMZ) in LGG patients treated in the randomized phase III trial
      EORTC 22033. As candidate biomarkers for these genotoxic treatments, we
      considered the DNA methylome of 410 DNA damage response (DDR) genes. We first
      identified 62 functionally relevant CpG sites located in the promoters of 24 DDR
      genes, using the LGG data from The Cancer Genome Atlas. Then we tested their
      association with outcome [progression-free survival (PFS)] depending on treatment
      in 120 LGG patients of EORTC 22033, whose tumors were mutant for isocitrate
      dehydrogenase 1 or 2 (IDHmt), the molecular hallmark of LGG. The results
      suggested that seven CpGs of four DDR genes may be predictive for longer PFS in
      one of the treatment arms that comprised MGMT, MLH3, RAD21, and SMC4. Most
      interestingly, the two CpGs identified for MGMT are the same, previously selected
      for the MGMT-STP27 score that is used to determine the methylation status of the
      MGMT gene. This score was higher in the LGG with 1p/19q codeletion, in this and
      other independent LGG datasets. It was predictive for PFS in the TMZ, but not in
      the RT arm of EORTC 22033. The results support the hypothesis that a high score
      predicts benefit from TMZ treatment for patients with IDHmt LGG, regardless of
      the 1p/19q status. This MGMT methylation score may identify patients who benefit
      from first-line treatment with TMZ, to defer RT for long-term preservation of
      cognitive function and quality of life.

PMID- 29368214
TI  - The meninges as barriers and facilitators for the movement of fluid, cells and
      pathogens related to the rodent and human CNS.
AB  - Meninges that surround the CNS consist of an outer fibrous sheet of dura mater
      (pachymeninx) that is also the inner periosteum of the skull. Underlying the dura
      are the arachnoid and pia mater (leptomeninges) that form the boundaries of the
      subarachnoid space. In this review we (1) examine the development of
      leptomeninges and their role as barriers and facilitators in the foetal CNS.
      There are two separate CSF systems during early foetal life, inner CSF in the
      ventricles and outer CSF in the subarachnoid space. As the foramina of Magendi
      and Luschka develop, one continuous CSF system evolves. Due to the lack of
      arachnoid granulations during foetal life, it is most likely that CSF is
      eliminated by lymphatic drainage pathways passing through the cribriform plate
      and nasal submucosa. (2) We then review the fine structure of the adult human and
      rodent leptomeninges to establish their roles as barriers and facilitators for
      the movement of fluid, cells and pathogens. Leptomeningeal cells line CSF spaces,
      including arachnoid granulations and lymphatic drainage pathways, and separate
      elements of extracellular matrix from the CSF. The leptomeningeal lining
      facilitates the traffic of inflammatory cells within CSF but also allows
      attachment of bacteria such as Neisseria meningitidis and of tumour cells as CSF
      metastases. Single layers of leptomeningeal cells extend into the brain closely
      associated with the walls of arteries so that there are no perivascular spaces
      around arteries in the cerebral cortex. Perivascular spaces surrounding arteries
      in the white matter and basal ganglia relate to their two encompassing layers of
      leptomeninges. (3) Finally we examine the roles of ligands expressed by
      leptomeningeal cells for the attachment of inflammatory cells, bacteria and
      tumour cells as understanding these roles may aid the design of therapeutic
      strategies to manage developmental, autoimmune, infectious and neoplastic
      diseases relating to the CSF, the leptomeninges and the associated CNS.

PMID- 29368215
TI  - Current state and perspectives in hydrogen production by Escherichia coli: roles
      of hydrogenases in glucose or glycerol metabolism.
AB  - Escherichia coli has been a robust host strain for much biological research, in
      particular, research in metabolic engineering, protein engineering, and
      heterologous gene expression. In this mini review, to understand bacterial
      hydrogen production by E. coli, the effect of glucose and glycerol metabolism on
      hydrogen production is compared, and the current approaches to enhance hydrogen
      production from glycerol as a substrate are reviewed. In addition, the argument
      from past to present on the functions of E. coli hydrogenases, hydrogenase 1,
      hydrogenase 2, hydrogenase 3, and hydrogenase 4 is summarized. Furthermore, based
      on the literature that the E. coli formate-hydrogen lyase is essential for
      bacterial hydrogen production via recombinant hydrogenases, research achievements
      from the past regarding heterologous production of hydrogenase are rethought.

PMID- 29368216
TI  - The role of soil bacterial community during winter fallow period in the incidence
      of tobacco bacterial wilt disease.
AB  - Bacterial wilt, caused by Ralstonia solanacearum, occurs occasionally during
      tobacco planting and potentially brings huge economic losses in affected areas.
      Soil microbes in different management stages play important roles in influencing
      bacterial wilt incidence. Studies have focused on the impacts of species
      diversity and composition during cropping periods on disease morbidity; however,
      the effects of the soil bacterial biomass, species diversity, species succession,
      and population interactions on morbidity remain unclear during non-cropping
      periods. In this study, we explored the soil bacterial communities in the non
      cropping winter fallow (WF) and cropping late growing (LG) periods under
      consecutive monoculture systems using 16S ribosomal RNA gene sequencing and qPCR
      and further analyzed their effects on tobacco bacterial wilt incidence. We found
      that the bacterial communities in the WF period were significantly different from
      those in the LG period based on detrended correspondence analysis and
      dissimilarity tests. Crop morbidity was significantly related to bacterial
      community structure and to the presence of some genera during WF and LG periods.
      These genera, such as Arthrobacter, Pseudomonas, Acidobacteria GP6, and
      Pasteuria, may be potential biological control agents for bacterial wilt. Further
      analysis indicated that low soil bacterial diversity during the WF period,
      decrease of bacterial interactions from the WF to LG periods, and low soil
      biomass during the LG period all have the potential to increase morbidity. In
      conclusion, an increase of soil bacterial diversity and control of some bacterial
      abundances in the WF period might be an effective approach in controlling
      bacterial wilt incidence.

PMID- 29368218
TI  - Articles You May Have Missed.

PMID- 29368217
TI  - Inducer-independent production of pectinases in Aspergillus niger by
      overexpression of the D-galacturonic acid-responsive transcription factor gaaR.
AB  - The transcription factor GaaR is needed for the expression of genes required for
      pectin degradation and transport and catabolism of the main degradation product,
      D-galacturonic acid (GA) in Aspergillus niger. In this study, we used the strong
      constitutive gpdA promoter of Aspergillus nidulans to overexpress gaaR in A.
      niger. Overexpression of gaaR resulted in an increased transcription of the genes
      encoding pectinases, (putative) GA transporters, and catabolic pathway enzymes
      even under non-inducing conditions, i.e., in the absence of GA. Exoproteome
      analysis of a strain overexpressing gaaR showed that this strain secretes highly
      elevated levels of pectinases when grown in fructose. The genes encoding exo
      polygalacturonases were found to be subjected to CreA-mediated carbon catabolite
      repression, even in the presence of fructose. Deletion of creA in the strain
      overexpressing gaaR resulted in a further increase in pectinase production in
      fructose. We showed that GaaR localizes mainly in the nucleus regardless of the
      presence of an inducer, and that overexpression of gaaR leads to an increased
      concentration of GaaR in the nucleus.

PMID- 29368219
TI  - Articles You May Have Missed.

PMID- 29368220
TI  - Understanding and improving decisions in clinical medicine (IV): prospects and
      challenges of nudging in healthcare.

PMID- 29368221
TI  - Successful Treatment of a Keratoacanthoma with Electrochemotherapy: A Case
      Report.
AB  - INTRODUCTION: Few studies have evaluated the efficacy of intralesional bleomycin
      injection combined with electroporation for the treatment of cutaneous tumors.
      However, the phenomenon that electroporation can enhance the cytotoxicity of
      bleomycin in vivo by 300-700 fold has been intensely investigated. CASE
      PRESENTATION: Keratoacanthoma in an 86-year-old patient was treated with
      intralesional bleomycin combined with electroporation. Treatment consisted of
      local application of shorty and intense electric pulses followed by local
      injection of bleomycin. Electroporation was always well tolerated by the patient,
      with no significant complaints, and the tumor had completely regressed by day 71
      of the follow-up. CONCLUSION: The results suggest that intralesional bleomycin
      injection combined with electroporation could represent a valid alternative
      therapeutic approach for the treatment of keratoacanthomas.

PMID- 29368222
TI  - Pressure-driven growth in strongly heterogeneous systems.
AB  - The pressure-driven growth model for advance of a foam front through an oil
      reservoir during foam improved oil recovery is considered: specifically the limit
      of strong heterogeneity in the reservoir permeability is treated, such that
      permeability variation with depth more than outweighs the tendency of the net
      pressure driving the front to decay with depth. This means that the fastest
      moving part of the front is not at the top of the solution domain, but rather
      somewhere in the interior. Moreover the location of the foam front on the top
      boundary of the system can no longer be specified as a boundary condition, but
      instead must be determined as part of the solution of the problem. Numerical
      solutions obtained from the pressure-driven growth model under these
      circumstances are compared with approximate analytic solutions. An early-time
      approximate solution is found to break down remarkably quickly (far more quickly
      than breakdown would occur in the analogous homogeneous system). Numerical
      solutions agree much better with local quasi-static solutions centred about local
      maxima in the front shape, each local maximum corresponding to a depth within the
      reservoir at which a high permeability stratum is found. These individual local
      solutions meet together at sharp concave corners to cover the entire depth of the
      foam front. As time continues to progress however, the system evolves towards a
      long-time, global quasi-static solution, corresponding to the fastest moving of
      the aforementioned local maxima. Additional key features of the predicted front
      shapes are elucidated. The foam front is found to meet the top boundary obliquely
      despite an established convention in pressure-driven growth that the front and
      top boundary should meet at right angles. In addition, at each sharp concave
      corner, discontinuous jumps are predicted in the path length that material points
      travel to reach either side of the corner. Moreover the long-time, global quasi
      static solution is found to admit smooth concavities, as opposed to the
      aforementioned sharp concave corners, which only tend to be prominent earlier on.

PMID- 29368224
TI  - A mild case of molybdenum cofactor deficiency defines an alternative route of
      MOCS1 protein maturation.
AB  - Molybdenum cofactor deficiency is an autosomal recessive inborn error of
      metabolism, which results from mutations in genes involved in Moco biosynthesis.
      Moco serves as a cofactor of several enzymes, including sulfite oxidase. MoCD is
      clinically characterized by intractable seizures and severe, rapidly progressing
      neurodegeneration leading to death in early childhood in the majority of known
      cases. Here we report a patient with an unusual late disease onset and mild
      phenotype, characterized by a lack of seizures, normal early development, a
      decline triggered by febrile illness and a subsequent dystonic movement disorder.
      Genetic analysis revealed a homozygous c.1338delG MOCS1 mutation causing a
      frameshift (p.S442fs) with a premature termination of the MOCS1AB translation
      product at position 477 lacking the entire MOCS1B domain. Surprisingly, urine
      analysis detected trace amounts (1% of control) of the Moco degradation product
      urothione, suggesting a residual Moco synthesis in the patient, which was
      consistent with the mild clinical presentation. Therefore, we performed
      bioinformatic analysis of the patient's mutated MOCS1 transcript and found a
      potential Kozak-sequence downstream of the mutation site providing the
      possibility of an independent expression of a MOCS1B protein. Following the
      expression of the patient's MOCS1 cDNA in HEK293 cells we detected two proteins:
      a truncated MOCS1AB protein and a 22.4 kDa protein representing MOCS1B.
      Functional studies of both proteins confirmed activity of MOCS1B, but not of the
      truncated MOCS1AB. This finding demonstrates an unusual mechanism of translation
      re-initiation in the MOCS1 transcript, which results in trace amounts of
      functional MOCS1B protein being sufficient to partially protect the patient from
      the most severe symptoms of MoCD.

PMID- 29368225
TI  - Sympathetic mechanisms in an animal model of vasovagal syncope.
AB  - PURPOSE: Individuals predisposed to vasovagal syncope may have different
      autonomic nervous system control mechanisms from those without predisposition to
      vasovagal events. To test this hypothesis, we investigated different sympathetic
      responses in a canine model of vasovagal syncope. METHODS: Left thoracotomy was
      performed on 20 mongrel dogs. The heart was exposed and a bolus of veratridine
      (15 MUg/kg), a neurotoxin which prevents the inactivation of sodium ion channels,
      was injected into the left atrium to induce a Bezold-Jarisch reflex-mediated
      vasovagal event, characterized by bradycardia, decreased inotropism, and
      hypotension. Electrocardiogram and blood pressure were continuously monitored.
      Neural activity was recorded from the left stellate ganglion. Plasma
      norepinephrine and acetylcholine levels were measured 30 s before and 30 s after
      veratridine injection. RESULTS: Veratridine resulted in rapid decreases in heart
      rate and blood pressure in all dogs, accompanied by increases in both
      norepinephrine and acetylcholine. Two types of neural activity (high-amplitude
      spike discharge activity and low-amplitude burst discharge activity) were
      recorded from the left stellate ganglion. Veratridine induced high-frequency
      spike discharge activity in some dogs (Group A), whereas spike discharge activity
      was scarce and relatively unresponsive to veratridine in the remaining dogs
      (Group B). Dogs in Group A had higher plasma norepinephrine levels (111.63 +/-
      15.1 vs. 48.11 +/- 33.81 ng/l, p = 0.002) and less intense drops in heart rate (-
      37 +/- 24 vs. - 84 +/- 28 bpm, p = 0.001) and blood pressure (systolic blood
      pressure, - 18 +/- 15 vs. - 37 +/- 13 mmHg, p = 0.009; diastolic blood pressure, 
      26 +/- 13 vs. - 45 +/- 13 mmHg, p = 0.005) compared to dogs in Group B.
      Similarly, heart rate post-veratridine was higher (102 +/- 23 vs. 69 +/- 22 bpm,
      p = 0.004), the veratridine-induced longest RR interval was shorter (0.7 [0.5
      0.8] vs. 1.2 [1.1-3.5] s, p < 0.001) and the diastolic and mean arterial
      pressures post-veratridine were higher (all p < 0.05) in dogs in Group A compared
      to those in Group B. CONCLUSIONS: Distinct sympathetic activation as represented
      by left stellate ganglion high-frequency spike discharge activity protected
      against bradycardia and hypotension in a canine model of vasovagal syncope. Our
      findings may have therapeutic implications.

PMID- 29368226
TI  - Lateral medullary infarction with cardiovascular autonomic dysfunction: an
      unusual presentation with review of the literature.
AB  - PURPOSE: We report an unusual case of lateral medullary infarction presenting
      with orthostatic hypotension with pre-syncope without vertigo or Horner's
      syndrome. METHODS: Case report with review of the literature. RESULTS: A 67-year
      old man presented with pre-syncope and ataxia without vertigo. Initial brain CT
      and MRI were normal. Neurological evaluation revealed right-beating nystagmus
      with left gaze, vertical binocular diplopia, right upper-extremity dysmetria,
      truncal ataxia with right axial lateropulsion, and right-facial and lower
      extremity hypoesthesia. Bedside blood pressure measurements disclosed orthostatic
      hypotension. He had normal sinus rhythm on telemetry and normal ejection fraction
      on echocardiogram. A repeat brain MRI disclosed an acute right dorsolateral
      medullary infarct. Autonomic testing showed reduced heart rate variability during
      paced deep breathing, attenuated late phase II and phase IV overshoot on Valsalva
      maneuver, and a fall of 25 mmHg of blood pressure at the end of a 10-min head-up
      tilt with no significant change in heart rate. These results were consistent with
      impaired sympathetic and parasympathetic cardiovascular reflexes. He was
      discharged to acute rehabilitation a week later with residual right dysmetria and
      ataxia. CONCLUSION: Lateral medullary infarctions are usually reported as partial
      presentations of classical lateral medullary syndrome with accompanying unusual
      symptoms ranging from trigeminal neuralgias to hiccups. Pre-syncope from
      orthostatic hypotension is a rare presentation. In the first 3-4 days, absence of
      early DWI MRI findings is possible in small, dorsolateral medullary infarcts with
      sensory disturbances. Physicians should be aware of this presentation, as early
      diagnosis and optimal therapy are associated with good prognosis.

PMID- 29368227
TI  - Intertwining personal and reward relevance: evidence from the drift-diffusion
      model.
AB  - In their seminal paper 'Is our self nothing but reward', Northoff and Hayes (Biol
      Psychiatry 69(11):1019-1025, Northoff, Hayes, Biological Psychiatry 69(11):1019
      1025, 2011) proposed three models of the relationship between self and reward and
      opened a continuing debate about how these different fields can be linked. To
      date, none of the proposed models received strong empirical support. The present
      study tested common and distinct effects of personal relevance and reward values
      by de-componenting different stages of perceptual decision making using a drift
      diffusion approach. We employed a recently developed associative matching
      paradigm where participants (N = 40) formed mental associations between five
      geometric shapes and five labels referring personal relevance in the personal
      task, or five shape-label pairings with different reward values in the reward
      task and then performed a matching task by indicating whether a displayed shape
      label pairing was correct or incorrect. We found that common effects of personal
      relevance and monetary reward were manifested in the facilitation of behavioural
      performance for high personal relevance and high reward value as socially
      important signals. The differential effects between personal and monetary
      relevance reflected non-decisional time in a perceptual decision process, and
      task-specific prioritization of stimuli. Our findings support the parallel
      processing model (Northoff & Hayes, Biol Psychiatry 69(11):1019-1025, Northoff,
      Hayes, Biological Psychiatry 69(11):1019-1025, 2011) and suggest that self
      specific processing occurs in parallel with high reward processing. Limitations
      and further directions are discussed.

PMID- 29368228
TI  - Do metacognitive judgments alter memory performance beyond the benefits of
      retrieval practice? A comment on and replication attempt of Dougherty, Scheck,
      Nelson, and Narens (2005).
AB  - A central question in the metacognitive literature concerns whether the act of
      making a metacognitive judgment alters one's memory for the information about
      which the judgment was made. Dougherty, Scheck, Nelson, and Narens (2005, Memory
      & Cognition, 33(6), 1096-1115) attempted to address this question by having
      participants make either retrospective confidence judgments (RCJs; i.e.,
      evaluations of past retrieval success), judgments of learning (JOLs; i.e.,
      predictions of future retrieval success), or no explicit judgments. When
      comparing final retrieval accuracy they found that accuracy was greater for items
      where participants had made JOLs compared with items that received RCJs or no
      judgment, suggesting that simply making a JOL can improve later memory
      performance. The present article presents results from four separate replication
      attempts that fail to duplicate this finding. Combined results provide compelling
      evidence that making a metacognitive judgment, regardless of the type, has no
      impact on later memory performance above and beyond retrieval practice.

PMID- 29368229
TI  - Viability and biocompatibility of an adhesive system for intrarenal embedding and
      endoscopic removal of small residual fragments in minimally-invasive stone
      treatment in an in vivo pig model.
AB  - PURPOSE: To evaluate the viability and biocompatibility of a novel, patented
      bioadhesive system for intrarenal embedding and retrieval of residual fragments
      after endoscopic lithotripsy. Complete stone clearance via active removal of
      residual fragments (RF) after intracorporeal laser lithotripsy may be time
      consuming and fail in many cases. Therefore, the novel adhesive has been
      developed and evaluated for the first time in an in vivo pig model in the present
      work. METHODS: Four female domestic pigs underwent flexible ureteroscopy (RIRS)
      or percutaneous nephrolithotomy (PNL) under general anesthesia (8 kidneys, 4 *
      RIRS, 4 * PNL) evaluating the bioadhesive system. INTERVENTIONS: RIRS without
      adhesive system (sham procedure, kidney I); 3 * RIRS using the bioadhesive system
      (kidneys II-IV); and 4 * PNL using the bioadhesive system (V-VIII). We
      endoscopically inserted standardized human stone probes followed by comminution
      using Ho:YAG lithotripsy. The bioadhesive (kidney II-VIII) was then applied and
      the adhesive-stone fragment complex extracted. After nephrectomy, all kidneys
      were evaluated by two independent, blinded pathologists. Endpoints were the
      procedure's safety and adhesive system's biocompatibility. RESULTS: We observed
      no substantial toxic effects. We were able to embed and remove 80-90% of
      fragments. However, because of the pig's hampering pyelocaliceal anatomy, a
      quantified, proportional assessment of the embedded fragments was compromised.
      CONCLUSIONS: For the first time, we demonstrated the proven feasibility and
      safety of this novel bioadhesive system for embedding and endoscopically removing
      small RF in conjunction with a lack of organ toxicity in vivo.

PMID- 29368230
TI  - Multiparametric ultrasound-targeted biopsy compares favorably to multiparametric
      MRI-transrectal ultrasound fusion-targeted biopsy on initial biopsy of men at
      risk for prostate cancer.
AB  - PURPOSE: The purpose this study is to evaluate the efficacy of multiparametric
      ultrasound-targeted biopsies in patients undergoing initial biopsy of the
      prostate for the suspicion of prostate cancer. MATERIALS AND METHODS: A total of
      167 patients who are biopsy naive underwent multiparametric ultrasound-targeted
      biopsy of the prostate. All patients had a transrectal ultrasound which included
      gray-scale evaluation and color Doppler evaluation. 12-core biopsies were
      performed on all patients, based on sextant anatomy; however, all cores were
      directed toward visually abnormal areas of the prostate as identified by
      multiparametric ultrasound, when such areas were present. RESULTS: Of 167
      patients undergoing biopsy, a total of 111 (66.5%) were positive for cancer. Of
      these, 78 (70.3%) had a Gleason grade >= 7 and 33 (29.7%) had a Gleason grade <=
      6. Of those undergoing radical prostatectomy 29 of 38 (76.3%) had biopsy Gleason
      grade >= 7, while nine of 38 (23.7%) had a Gleason grade <= 6. Only four of 38
      (10.5%) patients who had final pathologic staging underwent surgical therapy for
      disease of low-malignant potential (Gleason <= 6). CONCLUSION: On initial biopsy
      for prostate cancer, multiparametric ultrasound-targeted biopsy compares
      favorably to the published performance of multiparametric MRI-TRUS fusion
      targeted biopsy in terms of positive biopsy rate and the detection of disease of
      low-malignant potential.

PMID- 29368231
TI  - Surgical treatment for clinical node-positive bladder cancer patients treated
      with radical cystectomy without neoadjuvant chemotherapy.
AB  - OBJECTIVE: Growing literature supports good survival expectancies in bladder
      cancer (BCa) patients affected by clinical node metastases (cN+) treated with
      multimodal therapy. We evaluated the role of adjuvant chemotherapy in cN+BCa
      patients treated with radical cystectomy (RC) and pelvic lymph node dissection
      (PLND) without neoadjuvant chemotherapy (NAC). METHODS: We evaluated a total of
      192 patients with BCa and cN+. All patients were treated with RC and PLND without
      NAC between 2001 and 2013. Kaplan-Meier analyses and Cox regression analyses were
      used to assess the impact of adjuvant chemotherapy (ACT) on recurrence, cancer
      specific mortality (CSM) and overall mortality (OM) after surgery. RESULTS:
      Overall, 99 patients (51.6%) were found without node metastases at RC, while 18
      (9.4%), 58 (30.2%) and 17 (8.9%) patients were found pN1, pN2 and pN3,
      respectively. With a median follow-up of 48 months, in cN+ patients we recorded 5
      year recurrence, CSM and OM of 55, 53 and 51%, respectively. Overall, 36 (18.8%)
      patients were treated with adjuvant chemotherapy. At univariable analyses, ACT
      was associated with improved overall survival [Hazard ratio (HR): 0.42,
      confidence interval (CI) 0.20-0.86, p = 0.02) in pN+ subgroup only. These results
      were confirmed at multivariable analyses, where ACT was associated with improved
      CSS (HR: 0.45, CI 0.21-0.89, p = 0.03) and OS (HR: 0.37, CI 0.17-0.81, p = 0.01).
      CONCLUSIONS: We report good survival outcomes in cN+ patients treated with RC.
      The use of ACT after surgery increases survival expectancies, especially in those
      patients with pathological node disease. Our data need to be further evaluated in
      prospective setting.

PMID- 29368232
TI  - Comparison between open simple prostatectomy and green laser enucleation of the
      prostate for treating large benign prostatic hyperplasia: a single-centre
      experience.
AB  - PURPOSE: This study sought to compare perioperative outcomes and morbidities for
      open simple prostatectomy (OSP) and endoscopic green laser enucleation of the
      prostate (GreenLEP). METHODS: In a single department, all consecutive patients
      who underwent OSP between January 2005 and December 2010 were retrospectively
      reviewed, and all consecutive patients undergoing GreenLEP between July 2013 and
      January 2017 were prospectively enrolled. Perioperative data, information
      regarding early postoperative complications for up to 6 months and outcomes were
      collected and retrospectively compared. RESULTS: Overall, 204 patients were
      enrolled in each group. The baseline characteristics of patients in both groups
      were comparable. Intraoperative time was significantly longer for the OSP group
      than for the GreenLEP group (67 versus 60 min; p < 0.0001). The OSP group had
      significantly longer catheterisation (5 versus 2 days; p < 0.0001) and
      hospitalisation times (7 versus 2 days; p < 0.0001) than the GreenLEP group. The
      overall rate of complications was significantly higher after OSP than after
      GreenLEP (37.2 versus 20.6%; p = 0.0003); both Clavien-Dindo grade 3a
      complications (8.8 versus 0.98%) and Clavien-Dindo grade 3b complications (2.4
      versus 3.4%) were observed. The transfusion rate was higher after OSP than after
      GreenLEP (8.3 versus 0.5%; p = 0.0001). The rehospitalisation rate was similar
      for both groups (7.8 versus 8.3%; p = 0.99). CONCLUSIONS: The results of this
      single-centre cohort study confirm those of similar prior investigations
      addressing endoscopic enucleation of the prostate. Compared with OSP, GreenLEP
      may have a more desirable perioperative profile with lower morbidity. In
      contrast, GreenLEP and OSP were associated with similar 6-month rehospitalisation
      rates.

PMID- 29368234
TI  - Childhood Caregiving Roles, Perceptions of Benefits, and Future Caregiving
      Intentions Among Typically Developing Adult Siblings of Individuals with Autism
      Spectrum Disorder.
AB  - Typically developing siblings (TDS) of individuals with Autism Spectrum Disorder
      (ASD) frequently serve as caregivers during childhood, known as parentification,
      and primary caregivers for siblings in adulthood. In order to evaluate mechanisms
      linking these roles, we surveyed emerging-adult TDS (N = 108) about childhood
      parentification roles caring for parents and siblings, current perceptions of
      benefits associated with ASD and with engaging in parentification, and intention
      to provide future caregiving. We hypothesized that parent-focused parentification
      would negatively impact caregiving intention via perception of decreased benefits
      whereas sibling-focused parentification would positively impact intention via
      perception of increased benefits. Results indicate that parent-focused
      parentification is common and associated with fewer perceived benefits of
      caregiving and less intention to provide future caregiving. Prevention
      implications are discussed.

PMID- 29368233
TI  - Risk Factors for Self-injurious Behavior in an Inpatient Psychiatric Sample of
      Children with Autism Spectrum Disorder: A Naturalistic Observation Study.
AB  - Limited information about self-injurious behavior (SIB) is known for children and
      adolescents with Autism Spectrum Disorder (ASD) who require intensive behavioral
      health interventions. We examined risk-factors for SIB in 302 individuals with
      ASD (ages 4-20) admitted to six specialized psychiatric inpatient units. Seventy
      four percent were reported by a caregiver to display SIB, however, only 25% were
      observed to engage in daily SIB during hospitalization. Those exhibiting SIB
      across environments had significantly higher ratings on caregiver questionnaires
      of SIB severity. Tree-structured classification was used to develop and validate
      two predictive models, one indicating which inpatient youth with ASD are likely
      to have SIB and a second indicating which individuals with SIB at home are likely
      to continue in an inpatient setting.

PMID- 29368235
TI  - Dual Effect of Histidine on Polysorbate 20 Stability: Mechanistic Studies.
AB  - PURPOSE: L-Histidine (L-His) and polysorbate 20 (PS20) are two excipients
      frequently included in parenteral products to stabilize biotherapeutics. The
      objective of the current work was to investigate the impact of L-His on PS20
      stability in aqueous solutions when subjected to forced oxidation and accelerated
      stability testing. METHODS: The stability of PS20 in L-His buffer was compared
      with that in acetate buffer. Forced oxidation of PS20 in these two buffer systems
      was initiated by a free radical generator, 2,2'-azobis (2-amidinopropane)
      hydrochloride (AAPH), while accelerated stability tests were carried out at 40
      degrees C. Ultra-performance liquid chromatography mass spectrometry was utilized
      to monitor intact PS20 and to analyze degradation products. RESULTS: Our results
      demonstrate a dual effect of L-His on PS20 stability. During exposure to AAPH, L
      His protects PS20 from oxidation. Stable isotope labeling of L-His with 13C was
      employed for mechanistic investigations. The protection of L-His was abrogated
      when acetate was added to L-His buffer, implying that the anti-oxidative activity
      of L-His may be compromised by specific counter ions. The replacement of L-His by
      various His derivatives led to significant changes in the protection of PS20
      against AAPH-induced degradation. In contrast to forced degradation, the addition
      of L-His promoted oxidative PS20 degradation during accelerated storage at 40
      degrees C in solution, generating mainly short chain POE-laurates. CONCLUSION: L
      His exhibits a dual effect on the stability profile of PS20, protecting against
      AAPH-induced oxidation but promoting oxidative degradation during accelerated
      stability testing.

PMID- 29368236
TI  - Experimental study of sector and linear array ultrasound accuracy and the
      influence of navigated 3D-reconstruction as compared to MRI in a brain tumor
      model.
AB  - PURPOSE: Currently, intraoperative ultrasound in brain tumor surgery is a rapidly
      propagating option in imaging technology. We examined the accuracy and resolution
      limits of different ultrasound probes and the influence of 3D-reconstruction in a
      phantom and compared these results to MRI in an intraoperative setting (iMRI).
      METHODS: An agarose gel phantom with predefined gel targets was examined with
      iMRI, a sector (SUS) and a linear (LUS) array probe with two-dimensional images.
      Additionally, 3D-reconstructed sweeps in perpendicular directions were made of
      every target with both probes, resulting in 392 measurements. Statistical
      calculations were performed, and comparative boxplots were generated. RESULTS:
      Every measurement of iMRI and LUS was more precise than SUS, while there was no
      apparent difference in height of iMRI and 3D-reconstructed LUS. Measurements with
      3D-reconstructed LUS were always more accurate than in 2D-LUS, while 3D
      reconstruction of SUS showed nearly no differences to 2D-SUS in some
      measurements. We found correlations of 3D-reconstructed SUS and LUS length and
      width measurements with 2D results in the same image orientation. CONCLUSIONS:
      LUS provides an accuracy and resolution comparable to iMRI, while SUS is less
      exact than LUS and iMRI. 3D-reconstruction showed the potential to distinctly
      improve accuracy and resolution of ultrasound images, although there is a strong
      correlation with the sweep direction during data acquisition.

PMID- 29368237
TI  - The minimally invasive flexor carpi radialis approach: a new perspective for
      distal radius fractures.
AB  - The minimally invasive flexor carpi radialis approach can be used for volar
      locking plate fixation of distal radius fractures. After 15-mm incision on the
      lateral aspect of the FCR tendon and all structures but the radial artery are
      reclined ulnarly, a plate is inserted under the pronator quadratus just proximal
      to the "watershed line." The distal epiphyseal screws are put in place, and the
      proximal part of the plate is exposed by flexion of the wrist to put in place the
      proximal screws. No drainage or postoperative immobilization is used. It offers
      the advantage of preserving ligamentotaxis which facilitates the reduction, and
      the small size of the scar improves the esthetic result of the procedure. It is
      indicated for extra-articular fractures of the distal radius. In the case of an
      intraarticular fracture, an arthroscopy may be associated. In the case of a
      proximal diaphyseal extension of the fracture, a second proximal approach can be
      added in order to use a longer plate. Relative contraindications are comminuted
      articular fractures in elderly osteoporotic patients. Functional and radiological
      results are comparable to those obtained with the extented flexor carpi radialis
      approach. A conversion of the procedure for a larger incision is always possible
      in the case of a difficult reduction.

PMID- 29368238
TI  - Use of modular megaprosthesis in managing chronic end-stage periprosthetic hip
      and knee infections: Is there an increase in relapse rate?
AB  - BACKGROUND: Bone loss is a common problem in periprosthetic joint infection (PJI)
      scenarios. Modular megaprosthesis (MP) could offer a limb salvage solution in
      such situations. Concerns about risk of infection relapse, reinfection and
      implant longevity exist regarding MP use in cases of chronic PJI, rather than
      standard implants. We therefore sought to analyze our results with MP use in
      chronic PJI cases. METHODS: We performed a retrospective analysis of 29 MP
      patients. Inclusion criteria were the use of this type of modular megaimplant for
      reconstruction of segmental bone defects in chronically infected lower-extremity
      arthroplasties (hip or knee) and a minimum follow-up of 18 months. We evaluated
      the primary outcome of infection control or recurrence. The MPs were classified
      into 3 groups, according the bone segment replaced (proximal femur, distal femur
      or total femur). We further analyzed complications, pain, patient satisfaction
      and functional results. RESULTS: Mean age was 75 years; mean follow-up was 48
      months (range 18-82). The most frequently involved pathogens were coagulase
      negative staphylococci (62%). Polymicrobial infection was detected in 7 patients.
      Twenty-eight patients were managed with a two-stage approach. The infection-free
      rate at the end of follow-up was 82.8% (24 of 29 patients). Aside from infection
      relapse, the most frequent complication was dislocation. Final-point survival
      rate was 91.2% (CI 68.1-97.8). Clinical outcome data and satisfaction results
      were acceptable. CONCLUSION: According our data, MP is a useful tool in treating
      end-stage PJI cases, achieving acceptable eradication, satisfaction and implant
      survivorship rates.

PMID- 29368239
TI  - Ethical, Legal and Forensic Issues in Geriatric Psychiatry.
AB  - PURPOSE OF THE REVIEW: To evaluate the ethical, legal and forensic issues that is
      faced by the older adult population. RECENT FINDINGS: Many older individuals will
      face a host of ethical, medical and legal issues associated with their care. Most
      prominent among these issues are the maintenance of autonomy while ensuring their
      safety and the safety of individuals who care for them. Decisions regarding end
      of life including the formulation of advance directives add to the complexity of
      care for these older adults. A significant portion of individuals in the criminal
      justice system are aging and many of these individuals have psychiatric
      disorders. Their care is compromised due to the lack of appropriate services
      within criminal justice system for providing care for these individuals.
      CONCLUSIONS: Ethical, legal and forensic issues among older are not uncommon and
      complicate the care of these vulnerable individuals.

PMID- 29368240
TI  - Prevalence of mental diseases in Austria : Systematic review of the published
      evidence.
AB  - BACKGROUND: Addressing the growing burden of mental diseases is a public health
      priority. Nevertheless, many countries lack reliable estimates of the proportion
      of the population affected, which are crucial for health and social policy
      planning. This study aimed to collect existing evidence on the prevalence of
      mental diseases in Austria. METHODS: A systematic review was conducted using
      MeSH, EMTREE and free-text terms in seven bibliographic databases. In addition,
      the references of included papers and relevant Austria-specific websites were
      searched. Articles published after 1996 pertaining to the Austrian adult
      population and presenting prevalence data for mental diseases were included in
      the analysis. RESULTS: A total of 2612 records were identified in the database
      search, 19 of which were included in the analysis, 13 were community-based
      studies and 6 examined institutionalized populations. Sample sizes ranged from
      200 to 15,474. The evidence was centered around depression (n = 6, 32%), eating
      disorders (n = 4, 21%) and alcohol dependence (n = 3, 16%). While most studies (n
      = 10, 53%) used questionnaires and scales to identify mental diseases, seven
      studies used structured clinical interviews, and two studies examined use of
      psychotropic drugs. Due to the diversity of methodologies, no statistical pooling
      of prevalence estimates was possible. CONCLUSION: Information on the prevalence
      of mental diseases in Austria is limited and comparability between studies is
      restricted. A variety of diagnostic instruments, targeted populations and
      investigated diseases contribute to discrepancies in the prevalence rates. A
      systematic, large-scale study on the prevalence of mental diseases in Austria is
      needed for comprehensive and robust epidemiological evidence.

PMID- 29368241
TI  - Femoral access site closure without prior femoral angiography : A retrospective
      analysis.
AB  - AIMS AND BACKGROUND: Although guideline recommendations have shifted towards a
      transradial route, femoral puncture is still an established vascular access,
      especially for complex coronary interventions. The FemoSealTM vascular closure
      device (FVCD) helps to reduce femoral compression time and access site
      complications after removal of the catheter sheath. To ensure safe use, an
      angiography of the femoral artery prior to FVCD deployment is recommended by the
      manufacturer. We postulate that omitting this angiography does not relevantly
      increase the risk for vascular complications. METHODS AND RESULTS: In this
      retrospective analysis of an all-comers population (n = 1923) including patients
      receiving a percutaneous coronary intervention (PCI), we could show that combined
      vascular complication rates without femoral angiography were low (primary
      endpoint 4.6%) and comparable to a randomized clinical trial that did perform
      angiography of the vascular access site in a cohort of patients receiving
      diagnostic coronary angiography only. In addition to this analysis, we could
      demonstrate that patients with an acute coronary syndrome, receiving
      periprocedural anticoagulation or anti-platelet therapy had an increased risk for
      the formation of arterial pseudoaneurysms; however, we did not observe any
      ischemic vascular event after FVCD deployment. CONCLUSION: Closure of the femoral
      access site after coronary angiography using the FVCD can be safely performed
      without femoral angiography; however, due to an increased risk for the formation
      of pseudoaneurysms we recommend the transradial access in situations with
      increased bleeding risk.

PMID- 29368242
TI  - Serum proteomic profiling for autism using magnetic bead-assisted matrix-assisted
      laser desorption ionization time-of-flight mass spectrometry: a pilot study.
AB  - BACKGROUND: The pathogenesis of autism spectrum disorders remains elusive and
      currently there are no diagnostic or predictive biomarkers in autism available.
      Proteomic profiling has been used in a wide range of neurodevelopmental disorder
      studies, which could produce deeper perceptions of the molecular bases behind
      certain disease and potentially becomes useful in discovering biomarkers in
      autism spectrum disorders. METHODS: Serum samples were collected from autistic
      children about 3 years old in age (n = 32) and healthy controls (n = 20) in
      similar age and gender. The samples were identified specific proteins that are
      differentially expressed by magnetic bead-based pre-fractionation and matrix
      assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF
      MS). RESULTS: Eight protein peaks were significantly different in autistic
      children from the healthy controls (P < 0.0001). The two peaks with the most
      significant differences were 6428 and 7758 Da in size. CONCLUSION: According to
      differences in serum protein profiles between the autistic children and healthy
      controls, this study identified a set of differentially expressed proteins those
      are significant for further evaluation and might function as biomarkers in
      autism.

PMID- 29368243
TI  - Influence of culture media, pH and temperature on growth and bacteriocin
      production of bacteriocinogenic lactic acid bacteria.
AB  - There has been continued interest in bacteriocins research from an applied
      perspective as bacteriocins have potential to be used as natural preservative.
      Four bacteriocinogenic lactic acid bacteria (LAB) strains of Lactobacillus
      curvatus (Arla-10), Enterococcus faecium (JFR-1), Lactobacillus paracasei subsp.
      paracasei (JFR-5) and Streptococcus thermophilus (TSB-8) were previously isolated
      and identified in our lab. The objective of this study was to determine the
      optimal growth conditions for both LAB growth and bacteriocins production. In
      this study, various growth conditions including culture media (MRS and BHI),
      initial pH of culture media (4.5, 5.5, 6.2, 7.4 and 8.5), and incubation
      temperatures (20, 37 and 44  degrees C) were investigated for LAB growth measured
      as optical density (OD), bacteriocin activity determined as arbitrary unit and
      viability of LAB expressed as log CFU ml-1. Growth curves of the
      bacteriocinogenic LAB were generated using a Bioscreen C. Our results indicated
      that Arla-10, JFR-1, and JFR-5 strains grew well on both MRS and BHI media at
      growth temperature tested whereas TSB-8 strain, unable to grow at 20  degrees C.
      LAB growth was significantly affected by the initial pH of culture media (p <
      0.001) and the optimal pH was found ranging from 6.2 to 8.5. Bacteriocin activity
      was significantly different in MRS versus BHI (p < 0.001), and the optimal
      condition for LAB to produce bacteriocins was determined in MRS broth, pH 6.2 at
      37  degrees C. This study provides useful information on potential application of
      bacteriocinogenic LAB in food fermentation processes.

PMID- 29368244
TI  - Texture analysis as a predictor of radiation-induced xerostomia in head and neck
      patients undergoing IMRT.
AB  - PURPOSE: Image texture analysis (TA) is a heterogeneity quantifying approach that
      cannot be appreciated by the naked eye, and early evidence suggests that TA has
      great potential in the field of oncology. The aim of this study is to evaluate
      parotid gland texture analysis (TA) combined with formal dosimetry as a factor
      for predicting severe late xerostomia in patients undergoing radiation therapy
      for head and neck cancers. METHODS: We performed a retrospective analysis of
      patients treated at our Radiation Oncology Unit between January 2010 and December
      2015, and selected the patients whose normal dose constraints for the parotid
      gland (mean dose < 26 Gy for the bilateral gland) could not be satisfied due to
      the presence of positive nodes close to the parotid glands. The parotid gland
      that showed the higher V30 was contoured on CT simulation and analysed with LifeX
      Software(c). TA parameters included features of grey-level co-occurrence matrix
      (GLCM), neighbourhood grey-level dependence matrix (NGLDM), grey-level run length
      matrix (GLRLM), grey-level zone length matrix (GLZLM), sphericity, and indices
      from the grey-level histogram. We performed a univariate and multivariate
      analysis between all the texture parameters, the volume of the gland, the normal
      dose parameters (V30 and Mean Dose), and the development of severe chronic
      xerostomia. RESULTS: Seventy-eight patients were included and 25 (31%) developed
      chronic xerostomia. The TA parameters correlated with severe chronic xerostomia
      included V30 (OR 5.63), Dmean (OR 5.71), Kurtosis (OR 0.78), GLCM Correlation (OR
      1.34), and RLNU (OR 2.12). The multivariate logistic regression showed a
      significant correlation between V30 (0.001), GLCM correlation (p: 0.026), RLNU
      (p: 0.011), and chronic xerostomia (p < 0.001, R2:0.664). CONCLUSIONS: Xerostomia
      represents an important cause of morbidity for head and neck cancer survivors
      after radiation therapy, and in certain cases normal dose constraints cannot be
      satisfied. Our results seem promising as texture analysis could enhance the
      normal dose constraints for the prediction of xerostomia.

PMID- 29368245
TI  - Knocking down Cabin1 induces glomerular podocyte injury.
AB  - BACKGROUND: Podocyte damage exerts a key role in proteinuria. We have
      demonstrated that calcineurin-binding protein 1 (Cabin1) upregulated during
      podocyte injury, yet its function in podocyte is still unclear. METHODS: We
      established 5/6 nephrectomized rats and angiotensin II (AngII)-injured podocyte,
      as well as knocked down Cabin1 with siRNA in cultured podocytes. Rats were killed
      at 4 or 8 weeks after 5/6 nephrectomy. The localization of podocyte cytoskeleton
      was detected after immunofluorescence staining. Podocyte mitochondrial morphology
      was observed under electron microscopy. Podocyte mitochondrial transmembrane
      potential (MMP) was measured with MitoCapture kit. Cabin1 and cytochrome c
      protein expression were detected by western blot. RESULTS: Massive proteinuria,
      as well as obvious segmental glomerular sclerosis, was found in rats at 8 weeks
      after nephrectomy, accompanied with the disruption of synaptopodin. Moreover,
      mitochondria changed from large and ellipsoid shape to the small, long, and
      irregular shape in rats at 4 weeks after operation. At 8 weeks, mitochondria were
      swollen and cristae were remarkably dissolved. Compared to sham-operated rats,
      Cabin1 protein expression was obviously upregulated in rats at 8 weeks. AngII
      induced the decrease in MMP, as well as the overexpression of Cabin1 and
      cytochrome c protein in podocytes. Knocking down Cabin1 induced the disruption of
      F-actin and overexpression of cytochrome c (1.81 +/- 0.21 in siRNA group vs. 0.86
      +/- 0.11 in negative control group). CONCLUSIONS: Knocking down Cabin1 induces
      the disruption of cytoskeleton and mitochondrial dysfunction in podocyte. Cabin1
      could be a crucial factor in podocyte damage.

PMID- 29368246
TI  - Concomitant alteration in number and affinity of P2X and muscarinic receptors are
      associated with bladder dysfunction in early stage of diabetic rats.
AB  - OBJECTIVES: To investigate time course of bladder dysfunction and concurrent
      changes in number and affinity of the muscarinic and P2X receptor in the early
      stage of streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS:
      Diabetic rats were prepared by the intraperitoneal injection of 50 mg/kg of STZ
      to 7-week-old female Wistar rats. We performed recording of 24-h voiding behavior
      and cystometry at 1, 4, 8, and 12 weeks after the induction of diabetes. A muscle
      strip experiments with electrical field stimulation (EFS), carbachol, and
      alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP) were also
      performed at the same time-points. Additionally, concurrent changes in number and
      affinity of bladder muscarinic and P2X receptor were measured by a radioreceptor
      assay using [N-methyl-3H] scopolamine methyl chloride ([3H]NMS) and alpha,beta
      methylene-ATP (2,8-3H) tetrasodium salt ([3H]alpha,beta-MeATP). RESULTS: In STZ
      induced diabetic rats, polydipsic polyuric pollakiuria were noted on recording of
      24-h voiding behavior from early stage. Also, the residual urine volume markedly
      increased in diabetic rats on cystometry. In the muscle strip experiment, the
      detrusor contractions induced by EFS, carbachol, and alpha,beta-MeATP were
      enhanced in STZ-induced diabetic rats. Based on the radioreceptor assay, the
      maximum number of sites (Bmax) for the specific binding of [3H]NMS and
      [3H]alpha,beta-MeATP was concurrently increased in the bladder from diabetic
      rats. CONCLUSION: Increased bladder contractility is found in early stage of
      diabetic rats. Then, bladder dysfunction is associated with increased number of
      muscarinic and P2X receptors in STZ-induced diabetic rats.

PMID- 29368247
TI  - Astaxanthin attenuates contrast agent-induced acute kidney injury in vitro and in
      vivo via the regulation of SIRT1/FOXO3a expression.
AB  - PURPOSE: The study was processed to investigate the effect of astaxanthin (AST;
      3,3-dihydroxybeta, beta-carotene-4,4-dione) on the acute kidney injury induced by
      iohexol and the relationship with SIRT1/FOXO3a signal pathway. METHODS: Thirty
      male Sprague Dawley rats were randomly divided into five groups as follows:
      control group (CON; olive oil only), contrast media group, astaxanthin control
      group (100 mg/kg), low astaxanthin dose group (LAG, 50 mg/kg) and high
      astaxanthin dose group (HAG, 100 mg/kg). As followed, serum creatinine (SCr),
      blood urea nitrogen (BUN), the oxidative stress markers and apoptosis-related
      proteins were detected. Human proximal tubular epithelial cells (HK-2) were
      cultured in DMEM/F12 medium in vitro and then randomly divided into appropriate
      experimental groups: normal group (N), dimethyl sulfoxide (DMSO), iohexol group
      (I), iohexol + (1.0, 10.0 MUmol/L) astaxanthin group (I + LAST; I + HAST),
      iohexol + SIRT1 inhibitors (nicotinamide) group (NA) and iohexol + si-RNA FOXO3a
      group (si-RNA FOXO3a); when cultured for 24 h, cell proliferation ability was
      tested by cell counting kit (CCK-8), reactive oxygen species (ROS) were detected
      by flow cytometry and the expression of SIRT1 and FOXO3a were observed using
      western blot. RESULTS: At the end of the experiment, the levels of SCr, BUN and
      malondialdehyde (MDA) were all increased in the CM group. The LAG and HAG reduce
      superoxide anion (SOD) activity, catalase (CAT) activity, glutathione peroxidase
      (GPx) activity and glutathione (GSH) content, as well as SCr and BUN level.
      Moreover, apoptosis-associated proteins, caspase 3 p17, bax and bcl-2 were
      upregulated. In HK-2 cells, after adding iohexol, proliferation and intracellular
      ROS levels were significantly increased. Using astaxanthin in advance after the
      intervention, the result is opposite. SIRTl inhibitors NA can reduce the
      expression of SIRTl and decrease the expression of FOXO3a protein. Si-RNA FOXO3a
      reduces the expression of FOXO3a but had no significant effect on the expression
      of SIRT1. CONCLUSIONS: Our study demonstrates that the intervention of
      astaxanthin could attenuate the oxidative stress and apoptosis in contrast
      induced acute kidney injury (CI-AKI), and the SIRT1/FOXO3a pathway participates
      in the contrast-induced apoptosis of HK-2 cells. Finally, astaxanthin reduces CI
      AKI by suppression of apoptosis, which may be through inhibition of SIRT1/FOXO3a
      pathways.

PMID- 29368249
TI  - Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol)
      diacrylate Implants for Sustained Ocular Drug Delivery.
AB  - PURPOSE: To investigate the sustained ocular delivery of small and large drug
      molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants
      with varying pore forming agents. METHODS: Triamcinolone acetonide and ovalbumin
      loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were
      fabricated and characterised for chemical, mechanical, swelling, network
      parameters, as well as drug release and biocompatibility. HPLC-based analytical
      methods were employed for analysis of two molecules; ELISA was used to
      demonstrate bioactivity of ovalbumin. RESULTS: Regardless of PEGDA molecular
      weight or pore former composition all implants loaded with triamcinolone
      acetonide released significantly faster than those loaded with ovalbumin. Higher
      molecular weight PEGDA systems (700 Da) resulted in faster drug release of
      triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released
      over the 56-day time period was found to be bioactive. Increasing PEGDA molecular
      weight resulted in increased system swelling, decreased crosslink density (Ve),
      increased polymer-water interaction parameter (chi), increased average molecular
      weight between crosslinks (Mc) and increased mesh size (epsilon). SEM studies
      showed the porosity of implants increased with increasing PEGDA molecular weight.
      Biocompatibility showed both PEGDA molecular weight implants were non-toxic when
      exposed to retinal epithelial cells over a 7-day period. CONCLUSION:
      Photocrosslinked PEGDA implant based systems are capable of controlled drug
      release of both small and large drug molecules through adaptations in the polymer
      system network. We are currently continuing evaluation of these systems as
      potential sustained drug delivery devices.

PMID- 29368250
TI  - Prevention of Invasive Pneumococcal Disease: Problems Emerged After Some Years of
      the 13-Valent Pneumococcal Conjugate Vaccine Use.
AB  - Starting from 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) was
      introduced in several countries. This paper discusses some of the problems
      recently emerged after PCV13 use and their clinical impact. The impact of PCV13
      has been relevant and has saved millions of children and adults by severe
      infectious diseases. However, it seems likely that in the future, effectiveness
      of the vaccine might be even higher than that presently evidenced. This is
      because long-term administration of PCV13 to the pediatric population can favor a
      more extensive reduction of nasopharyngeal colonization with vaccine serotypes of
      both vaccinated and unvaccinated subjects and further reduce invasive
      pneumococcal disease in all the individuals (herd immunity). While waiting for
      new vaccines to be able to overcome the problem of a limited number of
      pneumococcal strains included in PCV13, it is recommended to increase
      pneumococcal vaccination coverage in the entire pediatric population.

PMID- 29368251
TI  - Imaging and anatomical features of ethmomaxillary sinus and its differentiation
      from surrounding air cells.
AB  - OBJECTIVE: The aim of this study was to investigate the imaging anatomical
      characteristics and clinical significance of the ethmomaxillary sinus (EMS).
      METHODS: The study included a total of 280 ENT Outpatient Department patients
      with nasal symptoms whose paranasal sinus CT scans were analyzed from January
      2012 to December 2016. The anatomical imaging characteristics of EMS were
      observed. RESULTS: EMS was observed in 23 of 280 patients, with an incidence of
      8.2%. Bilateral EMS appearance in 17 cases (73.9%) was significantly higher than
      that of unilateral EMS in 6 cases (26.1%) (P < 0.01). EMS occurs when there are
      anterior or anterior-inferior cells of the posterior ethmoidal sinus (PEs)
      extending toward the maxillary sinus (MS) and entering the MS through the
      maxillary hiatus rather than spreading from outside of the MS. EMS is surrounded
      by five walls, and the main position of EMS was invariably located in the
      posterior-superior corner of the MS and draining to the superior nasal meatus
      (SNM). EMS must be differentiated from SNM, sphenoid sinus, and retromaxillary
      pneumatization of PEs, because they may appear between the MS and the orbital
      floor. CONCLUSION: EMS was not a rare variation that should be careful
      identification during endoscopic sinus surgery. Accurately confirming EMS is the
      key to completely opening and removing lesions in the MS and EMS.

PMID- 29368252
TI  - Bilateral muscular slips between superior and inferior rectus muscles: case
      report with discussion on classification of accessory rectus muscles within the
      orbit.
AB  - Accessory rectus muscles have rarely been reported as muscular 'bands' or 'slips'
      originating from the common tendinous ring (annulus of Zinn) and inserting in
      atypical location. This group of muscles is innervated by the inferior branch of
      the oculomotor nerve, lies on lateral side of the optic nerve and inserts in
      rectus muscles. Since there are only few descriptions of such unusual findings in
      the medical literature, the anatomical data on accessory rectus muscles is
      limited. Furthermore, existing reports vary in terms of studied objects (cadavers
      or living subjects), medical history (absence or presence of ocular movement
      disorders or eye movement abnormalities) and details of anatomical description.
      This report complements earlier publications and provides complete anatomical
      description of the accessory rectus muscle observed bilaterally during the
      dissection of a 68-year-old male cadaver with no eye movement abnormalities
      reported in the medical history. The accessory rectus muscle was divided into two
      'slips' or 'heads'-superior and inferior-running in the sagittal plane (laterally
      to the optic nerve and the main trunk of the ophthalmic artery) and attached to
      the superior and inferior rectus muscles. Noticeable thickening of both superior
      and inferior rectus muscles at the insertion point of the accessory muscle heads
      was observed only in the sagittal plane. On both sides, the inferior head of the
      accessory rectus muscle was innervated by one of sub-branches derived from the
      inferior branch of the oculomotor nerve. No sub-branches to the superior head
      were macroscopically observed during the dissection. The classification,
      embryological background and clinical relevance of this variation have been
      discussed.

PMID- 29368253
TI  - The interface between child/adolescent and adult mental health services: results
      from a European 28-country survey.
AB  - Transition-related discontinuity of care is a major socioeconomic and societal
      challenge for the EU. The current service configuration, with distinct Child and
      Adolescent Mental Health (CAMHS) and Adult Mental Health Services (AMHS), is
      considered a weak link where the care pathway needs to be most robust. Our aim
      was to delineate transitional policies and care across Europe and to highlight
      current gaps in care provision at the service interface. An online mapping survey
      was conducted across all 28 European Countries using a bespoke instrument: The
      Standardized Assessment Tool for Mental Health Transition (SATMEHT). The survey
      was directed at expert(s) in each of the 28 EU countries. The response rate was
      100%. Country experts commonly (12/28) reported that between 25 and 49% of CAMHS
      service users will need transitioning to AMHS. Estimates of the percentage of
      AMHS users aged under 30 years who had has previous contact with CAMHS were most
      commonly in the region 20-30% (33% on average).Written policies for managing the
      interface were available in only four countries and half (14/28) indicated that
      no transition support services were available. This is the first survey of CAMHS
      transitional policies and care carried out at a European level. Policymaking on
      transitional care clearly needs special attention and further elaboration. The
      Milestone Study on transition should provide much needed data on transition
      processes and outcomes that could form the basis for improving policy and
      practice in transitional care.

PMID- 29368254
TI  - When addiction symptoms and life problems diverge: a latent class analysis of
      problematic gaming in a representative multinational sample of European
      adolescents.
AB  - The proposed diagnosis of Internet gaming disorder (IGD) in DSM-5 has been
      criticized for "borrowing" criteria related to substance addiction, as this might
      result in misclassifying highly involved gamers as having a disorder. In this
      paper, we took a person-centered statistical approach to group adolescent gamers
      by levels of addiction-related symptoms and gaming-related problems, compared
      these groups to traditional scale scores for IGD, and checked how groups were
      related to psychosocial well-being using a preregistered analysis plan. We
      performed latent class analysis and regression with items from IGD and
      psychosocial well-being scales in a representative sample of 7865 adolescent
      European gamers. Symptoms and problems matched in only two groups: an IGD class
      (2.2%) having a high level of symptoms and problems and a Normative class (63.5%)
      having low levels of symptoms and problems. We also identified two classes
      comprising 30.9% of our sample that would be misclassified based on their report
      of gaming-related problems: an Engaged class (7.3%) that seemed to correspond to
      the engaged gamers described in previous literature, and a Concerned class
      (23.6%) reporting few symptoms but moderate to high levels of problems. Our
      findings suggest that a reformulation of IGD is needed. Treating Engaged gamers
      as having IGD when their poor well-being might not be gaming related may delay
      appropriate treatment, while Concerned gamers may need help to reduce gaming but
      would not be identified as such. Additional work to describe the phenomenology of
      these two groups would help refine diagnosis, prevention and treatment for IGD.

PMID- 29368255
TI  - Reply to: "Letter to the Editor for the Manuscript the complex interplay of
      physical fitness, protein intake and vitamin D supplementation after bariatric
      surgery".

PMID- 29368257
TI  - Oxygen sensing and stem cell activation in the hypoxic carotid body.
AB  - The carotid body (CB) is the major arterial chemoreceptor responsible for the
      detection of acute decreases in O2 tension (hypoxia) in arterial blood that
      trigger hyperventilation and sympathetic activation. The CB contains O2-sensitive
      glomus (chief) cells, which respond to hypoxia with the release of transmitters
      to activate sensory nerve fibers impinging upon the brain respiratory and
      autonomic centers. During exposure to sustained hypoxia (for weeks or months),
      the CB grows several-fold in size, a response associated with acclimatization to
      high altitude or to medical conditions presenting hypoxemia. Here, I briefly
      present recent advances on the mechanisms underlying glomus cell sensitivity to
      hypoxia, in particular the role of mitochondrial complex I in acute oxygen
      sensing. I also summarize the properties of adult CB stem cells and of glomus
      cell-stem cell synapses, which contribute to CB hypertrophy in chronic hypoxia. A
      note on the relationship between hypoxic CB growth and tumorigenesis is included.
      Finally, the medical implications of CB pathophysiology are discussed.

PMID- 29368258
TI  - Tissue-derived scaffolds and cells for articular cartilage tissue engineering:
      characteristics, applications and progress.
AB  - There are many factors to consider in the field of tissue engineering. For
      articular cartilage repair, this includes seed cells, scaffolds and
      chondrotrophic hormones. This review primarily focuses on the seed cells and
      scaffolds. Extracellular matrix proteins provide a natural scaffold for cell
      attachment, proliferation and differentiation. The structure and composition of
      tissue-derived scaffolds and native tissue are almost identical. As such, tissue
      derived scaffolds hold great promise for biomedical applications. However,
      autologous tissue-derived scaffolds also have many drawbacks for transplantation,
      as harvesting autografts is limited to available donor sites and requires
      secondary surgery, therefore imparting additional damage to the body. This review
      summarizes and analyzes various cell sources and tissue-derived scaffolds applied
      in orthopedic tissue engineering.

PMID- 29368256
TI  - Immunopathogenesis and immunotherapy of multiple myeloma.
AB  - Despite the advent of novel therapies and improvements in survival, multiple
      myeloma (MM) remains an incurable disease. Thus, new treatment strategies
      including immunotherapies are needed for MM patients with stable disease after
      induction chemotherapy as well as for disease control in patients with advanced
      disease. However, profound immune dysregulation not only of B cells, but also of
      other immune cells such as natural killer cells, T cells, and dendritic cells and
      increase in the number of immunosuppressive cells, i.e., regulatory T and B cells
      and myeloid-derived suppressor cells, have been demonstrated in advanced MM
      patients, which may be involved in disease progression. Because of immune
      dysfunction, immunotherapies have not shown clinical efficacy in MM patients. It
      is therefore crucial to resolve immunosuppressive mechanisms and improve immune
      responses, especially in advanced MM patients. Recently, excellent clinical
      efficacy of new immunotherapeutic strategies such as immunomodulatory drug
      intensified monoclonal antibody treatment, immune checkpoint inhibitors, and
      chimeric antigen receptor T-cell therapy targeting B cell maturation antigen has
      been reported in advanced-stage MM patients. Those new treatments or their
      combination will improve prognosis and possibly point toward a cure for myeloma.

PMID- 29368259
TI  - Computational Fluid Dynamics Modeling of the Burr Orbital Motion in Rotational
      Atherectomy with Particle Image Velocimetry Validation.
AB  - Rotational atherectomy (RA) uses a high-speed rotating burr introduced via a
      catheter through the artery to remove hardened atherosclerotic plaque. Current
      clinical RA technique lacks consensus on burr size and rotational speed. The
      rotating burr orbits inside the artery due to the fluid force of the blood.
      Different from a common RA technique of upsizing burrs for larger luminal gain, a
      small burr can orbit to treat a large lumen. A 3D computational fluid dynamics
      (CFD) model was developed to simulate the burr motion and study the fluid flow
      and force in RA. A particle image velocimetry experiment was conducted to measure
      and validate the flow field including the radial and axial velocities and a pair
      of counter-rotating vortices near the burr equator in CFD. The hydraulic force on
      the burr and the contact force between the burr and the arterial wall were
      estimated by CFD. The contact force can be reduced by using smaller burr and
      lower rotational speed. Utilizing the small burr orbital motion has the potential
      to be an improved RA technique.

PMID- 29368260
TI  - Risk management adherence following genetic testing for hereditary cancer
      syndromes: a Singaporean experience.
AB  - Assessing adherence behavior among mutation carriers to cancer risk management
      guidelines is important for both service improvement and cost-effectiveness
      analyses, but such real-world data is often lacking. The present study aims to
      report adherence rates among mutation carriers in a recently established cancer
      genetics program in Singapore. We conducted a medical chart review of mutation
      carriers who had attended for genetic counseling and gathered data regarding risk
      management behavior, including cancer surveillance and/or risk-reducing surgery,
      and cancers subsequently detected. Of the 52 subjects included in the study, the
      majority were affected prior to genetic testing (78.8%) and had family history
      suggestive of a germline mutation (88.5%). The overall adherence rate was 96.2%,
      including 37 (74.0%) fully-adherent and 13 (26.0%) partially-adherent subjects,
      with five cancers subsequently detected. Among the 28 BRCA1/2 mutation carriers,
      adherence to breast cancer risk management was also high (89.3%), although uptake
      of risk-reducing bilateral salpingo-oophorectomy was not as common (60%). Whilst
      overall adherence in this cohort was high, BRCA1/2 mutation carriers may require
      targeted interventions to improve ovarian cancer risk management uptake.
      Additionally, further education among health professionals and the wider
      community regarding cancer genetics is needed to ensure the early identification
      of mutation carriers.

PMID- 29368261
TI  - APC mosaicism in a young woman with desmoid type fibromatosis and familial
      adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP) is usually caused by germline mutations in
      the adenomatous polyposis coli (APC) gene. The classic form is characterized by
      hundreds to thousands of adenomas in the colorectum and early onset colorectal
      cancer (CRC) if left untreated. FAP is also associated with multiple extra
      colonic manifestations such as gastroduodenal polyps, osteomas, epidermoid cysts,
      fibromas and desmoids. Most desmoid tumours in FAP patients occur intra
      abdominally. Approximately 15-20% of the APC mutations are de novo mutations.
      Somatic mosaicism has been reported in some sporadic cases of polyposis but is
      probably an underestimated cause of the disease. This case report presents the
      detection of a mosaic APC mutation in a 26-year-old woman who as a child had been
      diagnosed with desmoid type fibromatosis. FAP was suggested when she presented
      with extensive extra abdominal fibromatosis. Our findings indicate that APC
      mutations may be suspected in patients presenting with a desmoid regardless of
      its location. If there is clinical evidence that the patient has FAP, adenomas
      and colonic mucosa in addition to leukocyte DNA should be included in the
      screening, preferably using methods that are more sensitive than Sanger
      sequencing.

PMID- 29368262
TI  - Progression to polythythemia vera from familial thrombocytosis with germline JAK2
      R867Q mutation.

PMID- 29368263
TI  - Conformational determinants necessary for secretion of Paecilomyces thermophila
      beta-1,4-xylosidase that lacks a signal peptide.
AB  - In this study, we investigated the secretion mechanism of the hyper-secretion
      signal peptide-lacking beta-xylosidase PtXyl43, a non-classically secreted
      protein, from the fungus Paecilomyces thermophila in Escherichia coli BL21(DE3).
      PtXyl43 secretion is a two-step process, and the second step is accompanied by
      cell periplasmic leakage, indicating that PtXyl43 secretion is the result of semi
      specific secretion. Homology modeling of PtXyl43 suggested that PtXyl43 had a
      canonical GH43 family beta-xylosidase structure containing five blades. Seventeen
      blade deletions or circular mutants were designed to identify the conformational
      motif(s) involved in secretion. These mutants were expressed as recombinant,
      codon-optimized proteins in E. coli. Notably, only mutants containing blades 2-4
      were effectively secreted. Blades 2-4 are necessary for secretion, but it appears
      that blade 1 or 5 must be present to maintain the structure of blades 2-4.
      Simultaneous deletion of blades 1 and 5 dramatically reduces excretion. The
      covalent and sequential linking of blades of 2, 3 and 4 are important for the
      excretion of mutants, as separate blades of 2 and 3 or 3 and 4 abolishes
      excretion. Fusion with PtXyl43 promotes the excretion of GFP from the periplasm
      to the extracellular milieu, which suggested that PtXyl43 had the potential to
      carry proteins. This study provides new insights into secretory mechanism of
      secretable signal peptide-lacking proteins in E. coli. To our knowledge, this is
      the first to definitively identify the conformational determinants for secretion
      of a signal peptide-lacking GH43 family beta-xylosidase. This finding also has
      application potential for the secretion of recombinant proteins.

PMID- 29368264
TI  - Classification of micro-calcification in mammograms using scalable linear Fisher
      discriminant analysis.
AB  - Breast cancer is one of the major causes of death in women. Computer Aided
      Diagnosis (CAD) systems are being developed to assist radiologists in early
      diagnosis. Micro-calcifications can be an early symptom of breast cancer. Besides
      detection, classification of micro-calcification as benign or malignant is
      essential in a complete CAD system. We have developed a novel method for the
      classification of benign and malignant micro-calcification using an improved
      Fisher Linear Discriminant Analysis (LDA) approach for the linear transformation
      of segmented micro-calcification data in combination with a Support Vector
      Machine (SVM) variant to classify between the two classes. The results indicate
      an average accuracy equal to 96% which is comparable to state-of-the art methods
      in the literature. Graphical Abstract Classification of Micro-calcification in
      Mammograms using Scalable Linear Fisher Discriminant Analysis.

PMID- 29368265
TI  - Caste-fate determination primarily occurs after adult emergence in a primitively
      eusocial paper wasp: significance of the photoperiod during the adult stage.
AB  - Independent-founding paper wasps constitute a major group of primitively eusocial
      insects, and when caste-fate determination occurs in temperate species of these
      wasps, particularly regarding whether it occurs before or after emergence,
      remains unclear. No critical morphological differences occur between potential
      queens of the next generation (often called gynes) and workers in primitively
      eusocial insects. The gynes of temperate species are characterized by diapausing,
      and the nutrients available during the larval stage have often been believed to
      determine caste fate. Short days usually induce diapause in temperate nonsocial
      insects, although few investigations of the effects of day length on caste-fate
      determination in paper wasps have been conducted. By exposing individuals to
      different combinations of short and long days during the immature and adult
      stages, we show for the first time that short days during the adult stage (but
      not during the immature stage) facilitated caste-fate determination toward gynes
      in a paper wasp. Moreover, the decision to diapause partly depended on changes in
      the photoperiod during the pupal and adult stages. The size of the adult also
      affected caste-fate determination, with diapause more likely to occur in large
      adults, but this size effect did not occur when individuals were exposed to many
      short days during the pupal stage. In addition, all adults except for a small
      proportion of smaller individuals prepared for diapause under short days. These
      findings suggest that the photoperiod is a higher priority cue than adult size.

PMID- 29368267
TI  - [Prophylactic use of tranexamic acid in noncardiac surgery : Update 2017].
AB  - BACKGROUND: Minimising perioperative bleeding is a key goal of "patient blood
      management" programs. One component of respective strategies includes preventive
      inhibition of fibrinolysis using protease inhibitors, such as tranexamic acid
      (TXA). TXA inhibits plasminogen activation and plasmin-induced fibrin
      degradation. OBJECTIVES: The present article provides an overview of the existing
      literature and TXA applications in the prophylaxis of perioperative bleeding.
      METHODS: Literature search in PubMed/MEDLINE (U.S. National Library of
      Medicine(r), Bethesda, MD, USA). RESULTS: TXA reduces perioperative blood loss
      and transfusion requirements in several randomized controlled trials (RCTs) and
      meta-analyses in the field of hip and knee arthroplasty for both intravenous and
      topical use. Moreover, evidence favours use of TXA in complex spine surgery and
      reconstructive surgery (e. g. craniosynostosis in children). Single RCTs showed
      benefits of TXA in abdominal hysterectomy, open prostatectomy, liver surgery and
      actively bleeding trauma patients. For prophylaxis of peripartum haemorrhage
      (PPH) following vaginal delivery or Caesarean section, TXA cannot be routinely
      recommended, although evidence points to benefits in actively bleeding patients.
      A recommendation exists for the treatment of (active) PPH. For prophylactic
      perioperative administration, different dosage regimens exist for adults. Most
      often an initial i. v. bolus of 1 g or 10-15 mg/kg body weight with/without
      repetition after 6 h or continuous infusions over 8 h is administered. Increased
      rates of thromboembolic events were not noted. CONCLUSION: Protease inhibitors
      such as TXA reduce perioperative blood loss and transfusion requirements in
      selected surgical fields.

PMID- 29368268
TI  - A distributed delay approach for modeling delayed outcomes in pharmacokinetics
      and pharmacodynamics studies.
AB  - A distributed delay approach was proposed in this paper to model delayed outcomes
      in pharmacokinetics and pharmacodynamics studies. This approach was shown to be
      general enough to incorporate a wide array of pharmacokinetic and pharmacodynamic
      models as special cases including transit compartment models, effect compartment
      models, typical absorption models (either zero-order or first-order absorption),
      and a number of atypical (or irregular) absorption models (e.g., parallel first
      order, mixed first-order and zero-order, inverse Gaussian, and Weibull absorption
      models). Real-life examples were given to demonstrate how to implement
      distributed delays in Phoenix(r) NLMETM 8.0, and to numerically show the
      advantages of the distributed delay approach over the traditional methods.

PMID- 29368269
TI  - Out with the new, in with the old: Exogenous orienting to locations with
      physically constant stimulation.
AB  - Dominant methods of investigating exogenous orienting presume that attention is
      captured most effectively at locations containing new events. This is evidenced
      by the ubiquitous use of transient stimuli as cues in the literature on exogenous
      orienting. In the present study, we showed that attention can be oriented
      exogenously toward a location containing a completely unchanging stimulus by
      modifying Posner's landmark exogenous spatial-cueing paradigm. Observers searched
      a six-element array of placeholder stimuli for an onset target. The target was
      preceded by a decrement in luminance to five of the six placeholders, such that
      one location remained physically constant. This "nonset" stimulus (so named to
      distinguish it from a traditional onsetting transient) acted as an exogenous cue,
      eliciting patterns of facilitation and inhibition at the nonset location and
      demonstrating that exogenous orienting is not always evident at the location of a
      visual transient. This method eliminates the decades-long confounding of
      orienting to a location with the processing of new events at that location,
      permitting alternative considerations of the nature of attentional selection.

PMID- 29368266
TI  - Landscape of emerging and re-emerging infectious diseases in China: impact of
      ecology, climate, and behavior.
AB  - For the past several decades, the infectious disease profile in China has been
      shifting with rapid developments in social and economic aspects, environment,
      quality of food, water, housing, and public health infrastructure. Notably, 5
      notifiable infectious diseases have been almost eradicated, and the incidence of
      18 additional notifiable infectious diseases has been significantly reduced.
      Unexpectedly, the incidence of over 10 notifiable infectious diseases, including
      HIV, brucellosis, syphilis, and dengue fever, has been increasing. Nevertheless,
      frequent infectious disease outbreaks/events have been reported almost every
      year, and imported infectious diseases have increased since 2015. New pathogens
      and over 100 new genotypes or serotypes of known pathogens have been identified.
      Some infectious diseases seem to be exacerbated by various factors, including
      rapid urbanization, large numbers of migrant workers, changes in climate,
      ecology, and policies, such as returning farmland to forests. This review
      summarizes the current experiences and lessons from China in managing emerging
      and re-emerging infectious diseases, especially the effects of ecology, climate,
      and behavior, which should have merits in helping other countries to control and
      prevent infectious diseases.

PMID- 29368270
TI  - Vascularization of pancreatic decellularized scaffold with endothelial progenitor
      cells.
AB  - Vascularization remains a large obstacle for creating a functional pancreas
      tissue equivalent for transplantation. In this study, a pre-vascularized
      pancreatic decellularized scaffold was prepared through endothelializing with
      endothelial progenitor cells (EPCs) in a bioreactor, and the ability to
      regenerate new blood vessels was detected in vivo. Initially, pancreases of
      Sprague-Dawley (SD) rats were perfused with 1% Triton X-100 and 0.1% ammonium
      hydroxide to remove the cellular components while the intact vascular network was
      preserved. Then, the decellularized scaffold was reseed with EPCs, which were
      primarily characterized by dual staining for dil-labeled acetylated low-density
      lipoprotein (Dil-acLDL) and fluorescein isothiocyanate labeled ulex europaeus
      agglutinin 1 (FITC-UEA-1), to reconstruct the vascular network. Thus, a scaffold
      covered with EPCs in the vessel structure was created. After that, the scaffold
      was transplanted into the rat in vivo to observe the anastomosis with the host
      vascular network. The results showed that EPCs can be located around the blood
      vessel wall, and re-endothelialized scaffold connected with the host through new
      blood vessel formation earlier than the control group (p < 0.05). These findings
      all indicated that the pancreatic decellularized scaffold endothelialized with
      EPCs may be further applied to solve the problem of blood supply and support the
      function of insulin-secreting cells after in vivo transplantation.

PMID- 29368271
TI  - Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody
      Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings
      from a US Observational Cohort.
AB  - INTRODUCTION: To assess the relationship between low bone mineral density (BMD),
      anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity
      in patients with established rheumatoid arthritis (RA). METHODS: Patients
      enrolled in a single-center, observational cohort registry of patients with RA.
      Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR
      BMD), and anti-CCP2 antibody measurements at the same time point or within 6
      months. Anti-CCP2-immunoglobulin (Ig)G-positive (+) patients (>= 20 U/mL) were
      distributed into three equal groups (Gp1-3), representing increasing anti-CCP2
      antibody concentrations. Associations between BMD and anti-CCP2 antibody status
      and titer were explored in multivariate regression analyses controlling for
      covariates (including age, duration of RA, use of steroids, use of osteoporosis
      medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone
      loss was also explored. RESULTS: A total of 149 patients (all women) were
      included (47 anti-CCP2 antibody negative [-], 102 anti-CCP2+ [34?titer group]).
      Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti
      CCP2- group. DXR-BMD was lower in the anti-CCP2+ vs. the anti-CCP2- groups (Gp1-3
      vs. anti-CCP2-: P < 0.0001 for left and right hands). DXR-BMD decreased with
      increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with
      low DXR-BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).
      CONCLUSION: Among patients with established RA, data suggest that anti-CCP2+
      patients, particularly those with high anti-CCP2 antibody titers, have lower hand
      BMD, and patients with lower hand BMD are less likely to have low disease
      activity. FUNDING: Bristol-Myers Squibb. TRIAL REGISTRATION: Clinicaltrials.gov
      identifier, NCT01793103.

PMID- 29368273
TI  - Modeling of the contrast-enhanced perfusion test in liver based on the multi
      compartment flow in porous media.
AB  - The paper deals with modeling the liver perfusion intended to improve
      quantitative analysis of the tissue scans provided by the contrast-enhanced
      computed tomography (CT). For this purpose, we developed a model of dynamic
      transport of the contrast fluid through the hierarchies of the perfusion trees.
      Conceptually, computed time-space distributions of the so-called tissue density
      can be compared with the measured data obtained from CT; such a modeling feedback
      can be used for model parameter identification. The blood flow is characterized
      at several scales for which different models are used. Flows in upper hierarchies
      represented by larger branching vessels are described using simple 1D models
      based on the Bernoulli equation extended by correction terms to respect the local
      pressure losses. To describe flows in smaller vessels and in the tissue
      parenchyma, we propose a 3D continuum model of porous medium defined in terms of
      hierarchically matched compartments characterized by hydraulic permeabilities.
      The 1D models corresponding to the portal and hepatic veins are coupled with the
      3D model through point sources, or sinks. The contrast fluid saturation is
      governed by transport equations adapted for the 1D and 3D flow models. The
      complex perfusion model has been implemented using the finite element and finite
      volume methods. We report numerical examples computed for anatomically relevant
      geometries of the liver organ and of the principal vascular trees. The simulated
      tissue density corresponding to the CT examination output reflects a pathology
      modeled as a localized permeability deficiency.

PMID- 29368272
TI  - Concomitant high expression of ERalpha36, GRP78 and GRP94 is associated with
      aggressive papillary thyroid cancer behavior.
AB  - PURPOSE: Papillary thyroid cancer (PTC) is more common in women than in men. It
      has been suggested that estrogen may be involved in its development, as has
      previously been shown for breast, endometrial and ovarian cancer. The purpose of
      this study was to assess correlations between the expression of the estrogen
      receptor alpha36 (ERalpha36) and the glucose regulated proteins GRP78 and GRP94
      (chaperones involved in glycoprotein folding) and various PTC clinicopathological
      features, as well as to evaluate the potential usefulness of these three
      potential oncogenic proteins in the prediction of aggressive PTC behavior.
      METHODS: ERalpha36, GRP78 and GRP94 protein expression in 218 primary PTC tissues
      and PTC-derived BCPAP cells was examined using immunohistochemistry, Western
      blotting and immunocytochemistry. The proliferative, invasive and migrative
      capacities of BCPAP cells in which the respective genes were either exogenously
      over-expressed or silenced were assessed using BrdU incorporation and Transwell
      assays, respectively. RESULTS: We found that ERalpha36, GRP78 and GRP94 protein
      expression was upregulated in the primary PTC tissues tested. We also found that
      ERalpha36, GRP78 and GRP94 expression modulation affected the proliferation,
      invasion and migration of PTC-derived BCPAP cells. A positive correlation and a
      positive feedback loop were noted between ERalpha36, GRP78 and GRP94 protein
      expression in the primary PTC tissues and in BCPAP cells, respectively. High
      ERalpha36 expression in combination with a high GRP78/ GRP94 expression was found
      to have a stronger correlation with extrathyroid extension (ETE), lymph node
      metastasis (LNM), distant metastasis (DM) and high TNM stage than high ERalpha36
      expression in combination with either high GRP78 or high GRP94 expression (p =
      0.028 for ETE, p = 0.002 for DM and p <= 0.001 for LNM and high TNM stage) or
      high ERalpha36 expression alone (p < 0.001 for ETE, LNM, DM and high TNM stage).
      CONCLUSIONS: From our data we conclude that a concomitant high expression of
      ERalpha36, GRP78 and GRP94 is strongly associated with aggressive PTC behavior
      and may be used as a predictor for ETE, LNM, DM and high TNM stage.

PMID- 29368274
TI  - The association of AKNA gene polymorphisms with knee osteoarthritis suggests the
      relevance of this immune response regulator in the disease genetic
      susceptibility.
AB  - Recent studies have identified AKNA as a potential susceptibility gene for
      several inflammatory diseases. Here, we aimed to assess the potential association
      of AKNA polymorphisms with knee osteoarthritis (KOA) susceptibility in a Mexican
      population, following STREGA recommendations. From a DNA bank of 181 KOA patients
      and 140 healthy controls, two AKNA SNPs were genotyped using TaqMan probes. The
      association between KOA susceptibility and AKNA polymorphisms genotypes was
      evaluated by multivariated logistic regression analysis. Information regarding
      patients' inflammatory biomarkers levels was obtained and their association with
      AKNA polymorphisms genotypes was assessed by lineal regression. We found a
      positive association with the recessive inheritance model of both AKNA
      polymorphisms (A/A genotype for both) and KOA susceptibility adjusting by age,
      body mass index (BMI), gender and place of birth (OR = 2.48, 95% CI 1.09-5.65 for
      rs10817595 polymorphism; and OR = 4.96; 95% CI 2.421-10.2 for rs3748176
      polymorphism). Additionally these associations were also seen after stratifying
      patients by KOA severity and age. Furthermore the total leukocyte count was
      positively associated with rs10817595 AKNA polymorphism (beta = 1.39; 95% CI 0.44
      2.34) adjusting by age, BMI, gender, place of birth and disease severity. We
      suggest that regulatory and coding polymorphisms of the inflammatory modulator
      gene AKNA can influence the development of KOA. Further structural and functional
      studies might reveal the role of AKNA in OA and other rheumatic diseases.

PMID- 29368276
TI  - Investigating Pregnancy Outcomes After Abnormal Cell-Free DNA Test Results.
AB  - Cell-free DNA (cfDNA) testing has increased sensitivity and specificity compared
      to other prenatal screening methods, but invasive diagnostic testing (IDT) is
      recommended for confirmation. We performed a retrospective chart review of 39
      women with abnormal cfDNA results between March 2012 and September 2015 at an
      urban academic hospital to evaluate patient choice and pregnancy outcomes. We
      analyzed data using descriptive statistics, Fisher's exact tests, and Wilcoxon
      rank-sum tests. Median maternal age was 36.0 years [interquartile range (IQR) 31,
      39]; 64.1% of women (25/39) were advanced maternal age and 69.2% (27/39) had
      abnormal ultrasounds. Median gestational age at time of cfDNA testing was 18 3/7
      weeks [IQR 12 2/7, 20 5/7]. cfDNA results included trisomy 21 (89.7%, 35/39),
      trisomy 18 (7.7%, 3/39), and both trisomy 21/monosomy X (2.6%, 1/39). Of 39
      women, 22 (56.4%) continued and 10 (25.6%) terminated the pregnancy; six (15.4%)
      had fetal demises, and one was lost to follow-up. Of women continuing their
      pregnancies, 54.6% (12/22) declined further genetic counseling, and 77.3% (17/22)
      declined IDT. Only 14 women pursued IDT; not pursuing IDT was associated with
      continuing the pregnancy (Fisher's exact test, p = .001). All women terminating
      their pregnancy (90.0%, 9/10) pursued IDT or had major anomalies on ultrasound,
      suggesting that women considering termination undergo more confirmatory tests or
      already have high suspicion for an abnormal pregnancy.

PMID- 29368275
TI  - Genetic Counseling in the Era of Genomics: What's all the Fuss about?
AB  - As genomic sequencing becomes more widely available in clinical settings for
      diagnostic purposes, a number of genetic counseling issues are gaining
      precedence. The ability to manage these issues will be paramount as genetic and
      non-genetic healthcare professionals navigate the complexities of using genomic
      technologies to facilitate diagnosis and inform patient management. Counseling
      issues arising when counseling for diagnostic genomic sequencing were identified
      by four genetic counselors with 10 years of collective experience providing
      genetic counseling in this setting. These issues were discussed and refined at a
      meeting of genetic counselors working in clinical genomics settings in Melbourne,
      Australia. Emerging counseling issues, or variations of established counseling
      issues, were identified from the issues raised. Illustrative cases were selected
      where pre- and post-test genetic counseling was provided in clinical settings to
      individuals who received singleton or trio WES with targeted analysis. Counseling
      issues discussed in this paper include a reappraisal of how genetic counselors
      manage hope in the genomic era, informed consent for secondary use of genomic
      data, clinical reanalysis of genomic data, unexpected or unsolicited secondary
      findings, and trio sequencing. The authors seek to contribute to the evolving
      understanding of genetic counseling for diagnostic genomic sequencing through
      considering the applicability of existing genetic counseling competencies to
      managing emerging counseling issues and discussing genetic counseling practice
      implications.

PMID- 29368277
TI  - Utilization of the Tablet Application Proband in Pedigree Construction and
      Assessment.
AB  - Many medical institutions have converted to a digital model for record keeping
      due to the Health Information Technology for Economic and Clinical Health Act.
      This Act provides incentives to health care systems to accelerate and encourage
      the adoption of electronic health record (EHR) systems. The pedigree as a tool in
      medicine provides an efficient method to assess and represent an individual's
      health and family health risks that may otherwise not be apparent in the medical
      record in a clearly identifiable way (Schuette, J. L., & Bennett 2009). Many
      clinicians continue to construct pedigrees using pen and paper method despite
      findings of improved identification of at risk patients with similar electronic
      intake tools (Arar et al. in Personalized Medicine 2011 8:523-32). The goal of
      this study was to explore the patient and practitioner experience with electronic
      pedigree programs using Proband, an application developed at The Children's
      Hospital of Philadelphia for genetic counselors to construct pedigrees during
      genetic counseling sessions directly on iPads. The first part of this study
      looked at the patient experience and assessed time to take the pedigree and the
      impact of using an electronic pedigree tool on the relationship between
      participant and genetic counselor. This involved 50 participants and was compared
      with the traditional paper method of taking a pedigree. There was no statistical
      significance found between the two different mediums in accuracy, speed, and
      rapport with provider. The second part of the study assessed the usability of
      Proband by ten genetic counselors. Overall, the application received a system
      usability score of 90/100 with a majority (7/10) of counselors agreeing that they
      would use this application in their clinic. The positive outcome of this study
      encourages future work to assess the impact and usability of programs on a larger
      scale as they continue to integrate into current electronic health records.

PMID- 29368278
TI  - Peptide and Recombinant Allergen Vaccines for Food Allergy.
AB  - Food allergy is a significant public health problem, with no suitable treatments
      available for patients. Currently, patients are limited to avoidance and the use
      of readily available emergency medications. Immunotherapy is an appealing
      therapeutic strategy for inducing tolerance. Studies with whole native allergens
      have demonstrated the efficacy of immunotherapy for food allergy; however, the
      risk of IgE-mediated reactions with such treatment is significant. Advances in
      molecular biology techniques, including purification, sequencing, and cloning,
      have allowed researchers to identify specific allergen components and T cell
      binding epitopes. Support for the use of recombinant and peptide vaccines for
      food allergy comes from prior studies involving aeroallergens and hymenoptera
      venom. By manipulating allergen structure and IgE binding, allergenicity can be
      reduced, thereby reducing systemic reactions, making recombinant and peptide
      vaccines a safe and effective form of immunotherapy. Pre-clinical studies using
      in vitro and murine models demonstrated a more tolerant state following the use
      of these therapies. Studies with human subjects will be necessary to characterize
      the effects of recombinant and peptide food allergy vaccines and to demonstrate a
      safe treatment option for patients.

PMID- 29368280
TI  - In recognition of Ireland's clinical medical researchers: Noel G McElvaney, T
      Joseph McKenna, Noel Caplice and Bryan Hennessy.

PMID- 29368279
TI  - The clinical utility of pre-operative neutrophil-to-lymphocyte ratio as a
      predictor of outcomes in patients undergoing elective laparoscopic
      cholecystectomy.
AB  - BACKGROUND: In recent years, there has been an increasing trend towards day-case
      surgery for patients undergoing laparoscopic cholecystectomy (LC). We
      investigated the predictive value that pre-operative neutrophil-to-lymphocyte
      ratio (PNLR) had on surgical outcomes. METHODS: A review of all patients who
      underwent LC during a 6-year period in a single institution was performed and
      PNLR recorded. A PNLR cutoff value of 3 was utilised. We compared operation time,
      length of stay (LOS), and conversion to open between those with PNLR less and
      greater than 3. RESULTS: A total of 567 patients underwent elective LC. Those
      with PNLR>3 had associated prolonged operation time (p < 0.005), prolonged LOS (p
      < 0.005), and higher rates of conversion to open surgery (p < 0.005).
      CONCLUSIONS: PNLR correlates with outcomes following LC. It is useful in
      delineating patients that have higher risk of conversion or prolonged length of
      hospital stay and is helpful in assessing suitability of day-case surgery.

PMID- 29368281
TI  - Assessment of patient concerns: a review.
AB  - BACKGROUND: Patient-centred communication is the mainstay of the medical
      consultation. It includes the assessment of patient concerns and is important in
      building the doctor-patient therapeutic relationship. Our aim was to perform a
      literature review to identify relevance of patient concern assessment, to
      identify what concerns are encountered in various clinical settings and to
      explore the different methodologies used to obtain them. METHODS: A narrative
      review was performed. RESULTS: Addressing patient concerns is associated with
      increased patient satisfaction. Unvoiced concerns are associated with unresolved
      health issues and poor doctor-patient relationships. Different specialities have
      focused on different aspects of concern assessment. Patient concern assessment
      studies are mostly qualitative in nature. Not all qualitative methods give
      similar results. Interviews are more reliable sources of information than
      questionnaires as no one questionnaire captures all patient concerns. The
      location where interviews take place is also relevant. CONCLUSIONS: Assessing
      patient concerns is associated with positive outcomes. Patient concerns are
      handled differently by different clinical specialties. Various methodologies have
      been used for concern assessment. Interviews and questionnaires can often yield
      different results.

PMID- 29368282
TI  - Suboptimal lipid management before and after ischaemic stroke and TIA-the North
      Dublin Population Stroke Study.
AB  - BACKGROUND: Few population-based studies have assessed lipid adherence to
      international guidelines for primary and secondary prevention in stroke/transient
      ischaemic attack (TIA) patients. AIMS: This study aims to evaluate adherence to
      lipid-lowering therapy (LLT) guidelines amongst patients with ischaemic
      stroke/TIA. METHODS: Using hot and cold pursuit methods from multiple
      hospital/community sources, all stroke and TIA cases in North Dublin City were
      prospectively ascertained over a 1-year period. Adherence to National Cholesterol
      Education Programme (NCEP) III guidelines, before and after index ischaemic
      stroke/TIA, was assessed. RESULTS: Amongst 616 patients (428 ischaemic stroke,
      188 TIA), total cholesterol was measured following the qualifying event in 76.5%
      (471/616) and low-density lipoprotein (LDL) in 60.1% (370/616). At initial
      stroke/TIA presentation, 54.1% (200/370) met NCEP III LDL goals. Compliance was
      associated with prior stroke (odds ratio [OR] 2.19, p = 0.02), diabetes (OR 1.91,
      p = 0.04), hypertension (OR 1.57, p = 0.03), atrial fibrillation (OR 1.78, p =
      0.01), pre-event LLT (OR 2.85, p < 0.001) and higher individual LDL goal (p =
      0.001). At stroke/TIA onset, 32.7% (195/596) was on LLT. Nonetheless, LDL
      exceeded individual NCEP goal in 29.2% (56/192); 21.6% (53/245) warranting LLT
      was not on treatment prior to stroke/TIA onset. After index stroke/TIA, 75.9%
      (422/556) was on LLT; 15.3% (30/196) meeting NCEP III criteria was not prescribed
      a statin as recommended. By 2 years, actuarial survival was 72.8% and 11.9%
      (59/497) experienced stroke recurrence. No association was observed between
      initial post-event target adherence and 2-year outcomes. CONCLUSIONS: In this
      population-based study, LLT recommended by international guidelines was under
      used, before and after index stroke/TIA. Strategies to improve adherence are
      needed.

PMID- 29368283
TI  - Cumulative sum analysis of the learning curve for endoscopic resection of
      juvenile nasopharyngeal angiofibroma.
AB  - BACKGROUND: To determine the learning curve with cumulative sum analysis for
      endoscopic resection of juvenile nasopharyngeal angiofibroma (JNA) and
      investigate whether the surgeon's expertise is a risk factor for recurrence.
      MATERIALS AND METHODS: We reviewed the medical records of patients with JNA who
      underwent endoscopic or endoscopic-assisted surgery between 2006 and 2015. We
      used cumulative sum (Cusum) analysis to plot the learning curve for operation
      time versus chronological sequence, and verified the Cusum curve by risk-adjusted
      Cusum (RA-Cusum) analysis. We identified three phases of expertise. The
      recurrence rate was analyzed using the Kaplan-Meier method and log-rank tests. A
      multivariable Cox regression analysis was performed to identify the independent
      risk factors for recurrence. RESULTS: We included 154 JNA patients with a median
      age of 16 years. The surgeon overcame the learning curve after case 80 with
      increasing surgical efficiency and competence. The learning curve plotted by
      Cusum analysis divided the cases into three phases: phase 1, accumulation of
      initial experience (cases 1-41); phase 2, further accumulation of experience
      (cases 42-117); and phase 3, mastering the procedure (cases 118-154). Pearson's
      chi2 tests showed that tumor stage (P = 0.021), blood loss (P = 0.001), operation
      time (P < 0.001), and phase (P < 0.001) were associated with recurrence. The log
      rank test showed that time to recurrence was significantly shorter in phase 1
      than in phases 2 and 3. Blood loss and phase were independently prognostic
      factors for time to recurrence, with P values of 0.023 and 0.009, respectively.
      The RA-Cusum analysis identified two inflection points of the curve at case 44
      and 83, and verified the results of Cusum analysis. CONCLUSION: Surgical
      experience and competence with endoscopic resection affect the recurrence rate in
      JNA patients. LEVEL OF EVIDENCE: 4.

PMID- 29368284
TI  - Endoscopic gastrojejunostomy revision is more effective than medical management
      alone to address weight regain after RYGB.
AB  - BACKGROUND: Weight regain after bariatric roux-en-y gastric bypass affects up to
      30% of individuals. Revisional surgery is risky, and is typically avoided in
      favor of dietary and psychological management. Endoscopic gastrojejunostomy
      revision is a low-morbidity, outpatient procedure that may be more effective than
      medical management alone for regain after gastric bypass. METHODS: Two patient
      cohorts were retrospectively assembled. Both groups had gastric bypass, regained
      weight, and were cleared for revision by their surgeon, dietician, and
      psychologist. The revision group underwent the procedure, and the no-revision
      group did not, typically due to insurance issues. Weights from pre-bypass to 2
      years post-revision, obesity-related comorbidities, and intraoperative factors
      were collected and analyzed. RESULTS: There were 41 patients included in the
      revision group and 14 in the no-revision group. Up to the time of revision
      procedure, body mass index, and % excess weight loss between groups were similar.
      After revision, the groups diverged over a 2-year period, with improvement seen
      in the revision group and worsening in the no-revision group. The revision group
      showed overall improvement in comorbidities compared to the no-revision group.
      Analysis of intraoperative factors suggests that gastric pouch restriction in
      addition to stoma diameter reduction may promote weight loss. CONCLUSIONS: In
      this retrospective study, endoscopic revision provided significantly greater
      weight loss compared to medical management alone. Results show that revision can
      help resolve obesity-related comorbidities. Analysis of intraoperative factors
      suggests that pouch reduction at time of stoma revision may improve weight loss.

PMID- 29368285
TI  - Variation in laparoscopic anti-reflux surgery across England: a 5-year review.
AB  - BACKGROUND: Laparoscopic anti-reflux surgery (LARS) remains central to the
      management of gastro-oesophageal reflux disease but the scale and variation in
      provision in England is unknown. The aims of this study were firstly to examine
      the processes and outcomes of anti-reflux surgery in England and compare them to
      national guidelines and secondly to explore potential variations in practice
      nationally and establish peer benchmarks. METHODS: All adult patients who
      underwent LARSin England during the Financial years FY 2011/2012-FY 2016/2017
      were identified in the Surgeon's Workload Outcomes and Research Database (SWORD),
      which is based on the Hospital Episode Statistics (HES) data warehouse. Outcomes
      included activity volume, day-case rate, short-stay rate, 2- and 30-day
      readmission rates and 30-day re-operation rates. Funnel plots were used to
      identify national variation in practice. RESULTS: In total, 12,086 patients
      underwent LARS in England during the study period. The operation rate decreased
      slightly over the study period from 5.2 to 4.6 per 100,000 people. Most outcomes
      were in line with national guidelines including the conversion rate (0.76%), 30
      day re-operation rate (1.43%) and 2- and 30-day readmission rates (1.65 and
      8.54%, respectively). The day-case rate was low but increased from 7.4 to 15.1%
      during the 5-year period. Significant variation was found, particularly in terms
      of hospital volume, and day-case, short-stay and conversion rates. CONCLUSION:
      Although overall outcomes are comparable to studies from other countries, there
      is significant variation in anti-reflux surgery activity and outcomes in England.
      We recommend that units use these data to drive local quality improvement
      efforts.

PMID- 29368286
TI  - Why laparoscopists may opt for three-dimensional view: a summary of the full HTA
      report on 3D versus 2D laparoscopy by S.I.C.E. (Societa Italiana di Chirurgia
      Endoscopica e Nuove Tecnologie).
AB  - BACKGROUND: Three-dimensional view in laparoscopic general, gynaecologic and
      urologic surgery is an efficient, safe and sustainable innovation. The present
      paper is an extract taken from a full health technology assessment report on
      three-dimensional vision technology compared with standard two-dimensional
      laparoscopic systems. METHODS: A health technology assessment approach was
      implemented in order to investigate all the economic, social, ethical and
      organisational implications related to the adoption of the innovative three
      dimensional view. With the support of a multi-disciplinary team, composed of
      eight experts working in Italian hospitals and Universities, qualitative and
      quantitative data were collected, by means of literature evidence, validated
      questionnaire and self-reported interviews, applying a final MCDA quantitative
      approach, and considering the dimensions resulting from the EUnetHTA Core Model.
      RESULTS: From systematic search of literature, we retrieved the following
      studies: 9 on general surgery, 35 on gynaecology and urology, both concerning
      clinical setting. Considering simulated setting we included: 8 studies regarding
      pitfalls and drawbacks, 44 on teaching, 12 on surgeons' confidence and comfort
      and 34 on surgeons' performances. Three-dimensional laparoscopy was shown to have
      advantages for both the patients and the surgeons, and is confirmed to be a safe,
      efficacious and sustainable vision technology. CONCLUSIONS: The objective of the
      present paper, under the patronage of Italian Society of Endoscopic Surgery, was
      achieved in that there has now been produced a scientific report, based on a HTA
      approach, that may be placed in the hands of surgeons and used to support the
      decision-making process of the health providers.

PMID- 29368287
TI  - Gestural acquisition in great apes: the Social Negotiation Hypothesis.
AB  - Scientific interest in the acquisition of gestural signalling dates back to the
      heroic figure of Charles Darwin. More than a hundred years later, we still know
      relatively little about the underlying evolutionary and developmental pathways
      involved. Here, we shed new light on this topic by providing the first
      systematic, quantitative comparison of gestural development in two different
      chimpanzee (Pan troglodytes verus and Pan troglodytes schweinfurthii) subspecies
      and communities living in their natural environments. We conclude that the three
      most predominant perspectives on gestural acquisition-Phylogenetic Ritualization,
      Social Transmission via Imitation, and Ontogenetic Ritualization-do not
      satisfactorily explain our current findings on gestural interactions in
      chimpanzees in the wild. In contrast, we argue that the role of interactional
      experience and social exposure on gestural acquisition and communicative
      development has been strongly underestimated. We introduce the revised Social
      Negotiation Hypothesis and conclude with a brief set of empirical desiderata for
      instigating more research into this intriguing research domain.

PMID- 29368288
TI  - LY2963016 Insulin Glargine: A Review in Type 1 and 2 Diabetes.
AB  - Subcutaneous once-daily LY2963016 insulin glargine (LY insulin glargine)
      [Abasaglar(r) (EU); Basaglar(r) (USA)] has been approved in the EU as a
      biosimilar to reference insulin glargine (Lantus(r)), and in the USA as a follow
      on biologic to reference insulin glargine, for use in patients with type 1 or 2
      diabetes. Structural and functional characterization of LY insulin glargine in
      preclinical studies showed that it is similar to reference insulin glargine. In
      phase I euglycaemic clamp studies, LY insulin glargine demonstrated similar
      pharmacodynamic (including duration of action) and pharmacokinetic parameters to
      reference insulin glargine. In the phase III ELEMENT trials, LY insulin glargine
      and reference insulin glargine were noninferior to each other with respect to
      glycaemic control, indicating their equivalent efficacy, when administered with
      mealtime insulin in adults with type 1 diabetes or with oral antiglycaemic
      medications in adults with type 2 diabetes. LY insulin glargine was generally
      well tolerated, with a safety profile (including the risk of hypoglycaemia and
      immunogenicity) similar to that of reference insulin glargine and without any
      additional safety concerns identified. Basal insulin treatment status at baseline
      did not impact the relative efficacy, safety and immunogenicity of LY insulin
      glargine versus reference insulin glargine in the ELEMENT 1 and 2 trials. In
      conclusion, LY insulin glargine offers an additional basal insulin option for
      patients with type 1 or 2 diabetes, potentially at a lower cost.

PMID- 29368289
TI  - Liposomal Irinotecan Accumulates in Metastatic Lesions, Crosses the Blood-Tumor
      Barrier (BTB), and Prolongs Survival in an Experimental Model of Brain Metastases
      of Triple Negative Breast Cancer.
AB  - PURPOSE: The blood-tumor barrier (BTB) limits irinotecan distribution in tumors
      of the central nervous system. However, given that the BTB has increased passive
      permeability we hypothesize that liposomal irinotecan would improve local
      exposure of irinotecan and its active metabolite SN-38 in brain metastases
      relative to conventional irinotecan due to enhanced-permeation and retention
      (EPR) effect. METHODS: Female nude mice were intracardially or intracranially
      implanted with human brain seeking breast cancer cells (brain metastases of
      breast cancer model). Mice were administered vehicle, non-liposomal irinotecan
      (50 mg/kg), liposomal irinotecan (10 mg/kg and 50 mg/kg) intravenously starting
      on day 21. Drug accumulation, tumor burden, and survival were evaluated. RESULTS:
      Liposomal irinotecan showed prolonged plasma drug exposure with mean residence
      time (MRT) of 17.7 +/- 3.8 h for SN-38, whereas MRT was 3.67 +/- 1.2 for non
      liposomal irinotecan. Further, liposomal irinotecan accumulated in metastatic
      lesions and demonstrated prolonged exposure of SN-38 compared to non-liposomal
      irinotecan. Liposomal irinotecan achieved AUC values of 6883 +/- 4149 ng-h/g for
      SN-38, whereas non-liposomal irinotecan showed significantly lower AUC values of
      982 +/- 256 ng-h/g for SN-38. Median survival for liposomal irinotecan was 50
      days, increased from 37 days (p<0.05) for vehicle. CONCLUSIONS: Liposomal
      irinotecan accumulates in brain metastases, acts as depot for sustained release
      of irinotecan and SN-38, which results in prolonged survival in preclinical model
      of breast cancer brain metastasis.

PMID- 29368290
TI  - The clinical impairment assessment questionnaire: validation in Italian patients
      with eating disorders.
AB  - BACKGROUND: The Clinical Impairment Assessment (CIA) is a measure of functional
      impairment secondary to eating disorder symptoms. AIM: The aim of this study was
      to examine the psychometric proprieties of the Italian-language version of the
      CIA. METHODS: The tool was translated into Italian and administered to 259
      Italian-speaking in- and outpatients with eating disorders and 102 healthy
      controls. The clinical group also completed the Eating Disorder Examination
      Questionnaire (EDE-Q) and the Brief Symptom Inventory (BSI). RESULTS:
      Confirmatory factor analysis revealed a good fit for the original three-factor
      structure. Internal consistency was high for both the global CIA and all subscale
      scores, and test-retest reliability was acceptable. The high correlation between
      CIA and EDE-Q and BSI confirmed the convergent validity of the instrument. T test
      indicated higher raw scores on CIA in patients with eating disorders than healthy
      controls, and a cut-off score of 16 on the CIA discriminated between eating
      disorder and general psychopathology scores. Finally, global CIA and subscale
      scores were significantly higher in patients who reported objective bulimic
      episodes, purging behaviours, and excessive exercising than in those who did not;
      in underweight than in not-underweight patients, and in inpatients than
      outpatients, confirming the good known-groups validity of the tool. CONCLUSIONS:
      Overall, the study showed the good psychometric properties of the Italian version
      of the CIA, and validated its use in Italian-speaking eating disorder patients.
      LEVEL OF EVIDENCE: Level V, Descriptive study.

PMID- 29368292
TI  - Living with someone with an eating disorder: factors affecting the caregivers'
      burden.
AB  - We focused on carers of subjects suffering from eating disorders (ED), and
      studied the characteristics that mostly expose them to high levels of stress,
      anxiety, depression and expressed emotion, favoring the accommodation of the
      family system to the cared person. We administered the accommodation and enabling
      scale for eating disorders (AESED) questionnaire, the family questionnaire (FQ)
      and the depression, anxiety and stress scale (DASS-21) questionnaire to 97 carers
      of 62 ED patients, and investigated the carer's characteristics associated with
      the scores in the three questionnaires. A personal history of ED, being the
      primary carer, and caring for a person with a diagnosis of anorexia nervosa are
      the characteristics that contribute most to aggravate the carers' burden in terms
      of stress, anxiety, depression, accommodation and enabling. Our findings may help
      doctors to provide effective support to caregivers and eventually improve the
      treatment of subjects with ED.

PMID- 29368291
TI  - Expected benefits and motivation to weight loss in relation to treatment outcomes
      in group-based cognitive-behavior therapy of obesity.
AB  - PURPOSE: We aimed to determine cognitive drivers, expected to play a role in
      target reach and/or attrition in obesity programs. METHODS: We recorded the
      expected benefits of weight loss, weight targets, primary motivation for weight
      loss, perceived treatment needs, readiness and self-confidence to be successful
      and a battery of psychopathology questionnaires in 793 subjects with obesity (68%
      women; mean age 48.7; 46% obesity class III) enrolled into a group-based
      cognitive-behavioral treatment program. Their relevance on attrition and
      successful weight loss outcome were tested by logistic regression analysis.
      RESULTS: The expected benefits of weight loss scored very high in all physical,
      psychological and social areas, with differences between genders. Attrition rate
      was 24, 41 and 65% at 6-, 12-, and 24-month follow-up. Average weight loss was
      5.8 +/- 7.1 kg (- 4.8%) at 6 months, with 17% of cases (32% of continuers)
      maintaining weight loss > 10% at 24 months. After adjustment for confounders,
      attrition was reduced by concern for present health, motivation/consciousness of
      the importance of physical activity and need for support; treatment
      discontinuation was favored by concern for body image, by expectations for drug
      treatment or bariatric surgery, and by high-challenging weight loss targets. Male
      gender, higher BMI and concern for present health predicted weight loss > 10%,
      whereas concern for body appearance was associated with lower probability of
      attaining the desired weight loss targets. CONCLUSION: A more precise definition
      of needs and expectations might help tailor treatment to individual patients, but
      attrition rates and target reach remain difficult to predict. LEVEL OF EVIDENCE:
      Level V, descriptive studies.

PMID- 29368294
TI  - Application of Strict Criteria for Noninvasive Follicular Thyroid Neoplasm with
      Papillary-Like Nuclear Features and Encapsulated Follicular Variant Papillary
      Thyroid Carcinoma: a Retrospective Study of 50 Tumors Previously Diagnosed as
      Follicular Variant PTC.
AB  - Noninvasive follicular thyroid neoplasm with papillary-like nuclear features
      (NIFTP) was recently proposed as a designation for a subset of follicular variant
      papillary thyroid carcinoma (FVPTC). Encapsulated FVPTC has been shown to be a
      fairly indolent tumor, and NIFTP are expected to represent the most indolent
      subset of these tumors. Many of the exclusion criteria for NIFTP related to
      architecture and a lack of psammoma bodies are designed to preclude the inclusion
      of more aggressive non-FVPTC tumors in this indolent group and also exclude the
      diagnosis of FVPTC. In addition to strict application of histologic features to
      ensure that NIFTP represents a subset of encapsulated FVPTC without invasion,
      other exclusion criteria including high mitotic activity and necrosis may also
      lead to a lack of one-to-one correlation between the diagnosis of NIFTP and
      encapsulated FVPTC without invasion. In this series, 50 cases previously
      diagnosed as FVPTC over a 2-year period from a large academic center are
      retrospectively reviewed for reclassification as NIFTP. Additionally, cases not
      meeting criteria for NIFTP are more accurately classified using the most up to
      date WHO criteria. Prior BRAF V600E mutation testing was examined for these
      tumors when available. Seventeen of 50 (34%) tumors met criteria for
      classification as NIFTP and, 17 (34%) were classified as encapsulated FVPTC with
      invasion. Strict application of architectural features led to classification of
      12 (24%) tumors as non-FVPTC with a variety of more aggressive designations.
      Tumors classified as NIFTP and encapsulated FVPTC with invasion lacked lymph node
      metastases (0/4; 0/7, respectively) and BRAF mutations (0/12; 0/13,
      respectively). In contrast, infiltrative FVPTC, encapsulated PTC with or without
      invasion, and conventional PTC showed more aggressive features with lymph node
      metastases and BRAF V600E mutations. One case not meeting criteria for NIFTP
      maintained the diagnosis of encapsulated FVPTC without invasion but demonstrated
      significant mitotic activity (three mitoses/ten HPF) and lacked lymph node
      metastases and BRAF V600E mutation. These findings demonstrate the importance of
      using strict criteria, especially the lack of true papillary architecture, for
      the diagnosis of NIFTP and encapsulated FVPTC to ensure that only truly indolent
      tumors will be included in these diagnoses and to allow tumors with potential for
      more aggressive behavior to be appropriately treated.

PMID- 29368295
TI  - Does Foraging Experience Affect the Responses of the Predator Dicyphus hesperus
      Knight to Prey-Induced Volatiles?
AB  - The predatory mirid bug Dicyphus hesperus Knight (Hemiptera: Miridae) is a native
      North America species with high potential as biological control agent of the
      potato psyllid, Bactericera cockerelli Sulcer (Hemiptera: Triozidae), which is a
      major solanaceous pest. Olfactory responses of D. hesperus to volatiles from
      plants infested with the potato psyllid and the effect of foraging experience on
      search efficacy were studied. Using a Y-tube olfactometer, we found that naive
      females had no preference in choice tests between either uninfested tomato
      plants, or Ephestia kuehniella Zeller (Lepidoptera: Pyralidae) eggs-infested
      plants, and clean air. Naive females showed an innate positive response to B.
      cockerelli-infested plants, but no preference when given a choice between
      uninfested tomato plants and E. kuehniella eggs-infested plants. However, females
      with experience of foraging on B. cockerelli-infested plants showed a strong
      preference for B. cockerelli-infested plants (78% response) in choice tests with
      uninfested tomato plants and E. kuehniella eggs-infested plants. Implications of
      learning for augmentative biological control are discussed.

PMID- 29368293
TI  - Epidemiology, clinical presentation and diagnosis of non-functioning pituitary
      adenomas.
AB  - PURPOSE: Non-functioning pituitary adenomas (NFPAs) are benign pituitary
      neoplasms that do not cause a hormonal hypersecretory syndrome. An improved
      understanding of their epidemiology, clinical presentation and diagnosis is
      needed. METHOD: A literature review was performed using Pubmed to identify
      research reports and clinical case series on NFPAs. RESULTS: They account for 14
      54% of pituitary adenomas and have a prevalence of 7-41.3/100,000 population.
      Their standardized incidence rate is 0.65-2.34/100,000 and the peak occurence is
      from the fourth to the eighth decade. The clinical spectrum of NFPAs varies from
      being completely asymptomatic to causing significant hypothalamic/pituitary
      dysfunction and visual field compromise due to their large size. Most patients
      present with symptoms of mass effect, such as headaches, visual field defects,
      ophthalmoplegias, and hypopituitarism but also hyperprolactinaemia due to
      pituitary stalk deviation and less frequently pituitary apoplexy. Non-functioning
      pituitary incidentalomas are found on brain imaging performed for an unrelated
      reason. Diagnostic approach includes magnetic resonance imaging of the sellar
      region, laboratory evaluations, screening for hormone hypersecretion and for
      hypopituitarism, and a visual field examination if the lesion abuts the optic
      nerves or chiasm. CONCLUSION: This article reviews the epidemiology, clinical
      behaviour and diagnostic approach of non-functioning pituitary adenomas.

PMID- 29368296
TI  - Programs for Preventing Depression in Adolescence: Who Benefits and Who Does Not?
      An Introduction to the Supplemental Issue.
AB  - We introduce this supplemental issue of Prevention Science, which brings together
      a set of papers from leading investigators who have conducted trials testing
      whether intervention programs prevent adolescent depression. Using data from
      these trials, these papers explore a series of factors that might account for
      variation in intervention benefit, employing several novel methods for assessing
      effect heterogeneity. These studies follow two general paradigms: three papers
      report findings from single randomized preventive intervention trials, while the
      remaining papers develop and apply new methods for combining data from multiple
      studies to evaluate effect heterogeneity more broadly. Colleagues from NIMH and
      SAMHSA also provide commentaries on these studies. They conclude that synthesis
      of findings from multiple trials holds great promise for advancing the field, and
      progress will be accelerated if collaborative data sharing becomes the norm
      rather than the exception.

PMID- 29368297
TI  - Correction to: Knowing Every Child: Validation of the Holistic Student Assessment
      (HSA) as a Measure of Social-Emotional Development.
AB  - The Holistic Student Report was reported online as open source. It is not. Any
      use in part or in whole in any form or version has to be approved in writing.

PMID- 29368298
TI  - A web-based multidomain lifestyle intervention with connected devices for older
      adults: research protocol of the eMIND pilot randomized controlled trial.
AB  - BACKGROUND: Multidomain interventions composed of nutritional counseling,
      exercise and cognitive trainings have shown encouraging results as effective
      preventive strategies delaying age-related declines. However, these interventions
      are time- and resource-consuming. The use of Information and Communication
      Technologies (ICT) might facilitate the translation from research into real-world
      practice and reach a massive number of people. AIM: This article describes the
      protocol of the eMIND study, a randomized controlled trial (RCT) using a web
      based multidomain intervention for older adults. METHODS: One hundred and twenty
      older adults (>= 65 years), with a spontaneous memory complaint, will be randomly
      assigned to a six-month web-based multidomain (nutritional counseling, physical
      and cognitive trainings) intervention group with a connected accelerometer
      (number of steps, energy expenditure), or to a control group with access to
      general information on healthy aging plus the accelerometer, but no access to the
      multidomain intervention. The main outcome is the feasibility/acceptability of
      the web-based intervention. Secondary clinical outcomes include: cognitive
      functions, physical performance, nutritional status and cost-effectiveness.
      RESULTS: We expect a high amount of adherers (ie, > 75% compliance to the
      protocol) to reflect the feasibility. Acceptability, assessed through interviews,
      should allow us to understand motivators and barriers to this ICT intervention.
      We also expect to provide data on its effects on various clinical outcomes and
      efficiency. CONCLUSION AND DISCUSSION: The eMIND study will provide crucial
      information to help developing a future and larger web-based multidomain
      lifestyle RCT, which should facilitate the translation of this ICT intervention
      from the research world into real-life clinical practice for the healthcare of
      older adults.

PMID- 29368299
TI  - Autophagic flux is essential for the downregulation of D-dopachrome tautomerase
      by atractylenolide I to ameliorate intestinal adenoma formation.
AB  - Colorectal cancer is generally believed to progress through an adenoma -
      carcinoma sequence. Adenomatous polyposis coli (APC) mutations serve as the
      initiating event in adenoma formation. The ApcMin/+ mouse harbors a mutation in
      the APC gene, which is similar or identical to the mutation found in individuals
      with familial adenomatous polyposis and 70% of all sporadic CRC cases. Autophagy
      is a constitutive process required for proper cellular homeostasis. However, its
      role in intestinal adenoma formation is still controversial. Atractylenolide I
      (AT1) is a sesquiterpenoid that possesses various clinically relevant properties
      such as anti-tumor and anti-inflammatory activities. The role of AT1 on adenoma
      formation was tested in ApcMin/+ mice and its underlying mechanism in regulating
      autophagy was documented. D-dopachrome tautomerase (D-DT) was identified as a
      potential target of AT1 by an proteomics-based approach. The effects of p53
      modification on autophgic flux was monitored in p53-/- and p53+/+ HCT116 cells.
      Small interfering RNA was used to investigate the function of Atg7 and D-DT on
      autophagy programme induce by AT1. AT1 effectively reduced the formation of
      adenoma and downregulated the tumorigenic proteins in ApcMin/+ mice. Importantly,
      AT1 stimulated autophagic flux through downregulating acetylation of p53.
      Activation of Sirt1 by AT1 was essential for the deacetylation of p53 and
      downregulation of D-DT. The lowered expression of COX-2 and beta-catenin by AT1
      were partly recovered by Atg7 knockdown. AT1 activates autophagy machinery to
      downregulate D-DT and reduce intestinal adenoma formation. This discovery
      provides evidence in vivo and in vitro that inducing autophagy by natural
      products maybe a potential therapy to ameliorate colorectal adenoma formation.

PMID- 29368300
TI  - Hyperuricosuric calcium urolithiasis.
AB  - Hyperuricosuric calcium urolithiasis is a condition of mixed calcium oxalate
      stones characterized by hyperuricosuria either in isolation or in conjunction
      with other risk factors for calcium oxalate stones such as hypercalciuria,
      hyperoxaluria, and hypocitraturia. There are three proposed physicochemical
      models of pathogenesis where urate in its crystalline phase via heterogeneous
      nucleation, in its colloidal phase via removal of crystallization inhibitors, and
      in solution via precipitation crystallization, can all increase propensity to
      calcium oxalate precipitation. Regardless of the model, the phenomenologic
      observation of urate increasing calcium oxalate precipitation appears solid.
      Another supporting factor are retrospective data analysis and prospective trials
      showing uric acid lowering reduces stones events in hyperuricosuric calcium stone
      formers. Due to the heterogeneity of pathogenesis of calcium oxalate stones in
      the unselected stone-formers, association cannot be demonstrated between uric
      acid excretion rate and risk of kidney stone the general population. In calcium
      oxalate stoners with isolated hyperuricosuria or hyperuricosuria in combination
      with other calcium stone risks where treatment of these traditional risks fails
      to reduce stone formation, urate acid lowering should be cautiously attempted.
      More refinement of pathogenic models and prospective controlled trials in
      phenotypically defined subgroups of subjects with calcium oxalate urolithiasis
      will be informative.

PMID- 29368301
TI  - Comparison of Some Soil Fungi in Bioremediation of Herbicide Acetochlor Under
      Agitated Culture Media.
AB  - In this study, we aimed to find out the biodegradation efficiency of some soil
      fungi types on herbicide acetochlor with acetochlor active material, chemical
      oxygen demand (COD), biochemical oxygen demand (BOD5) and total organic carbon
      (TOC) parameters. We also try to determine the population dynamics of these fungi
      via turbidity. The fungi cultures were isolated from agricultural field in in
      Thrace region of Turkey. Each fungi enriched in malt extract broth media and 1 mL
      of these enriched media was inoculated into 100 mL of acetochlor solutions that
      suggested for using application concantrations in agricultural field for farmers
      (11000 mg L-1) for sunflower and corn agriculture. Bioremediation results of
      acetochlor have shown different results according to the types of fungi. Our
      results indicate that Tolypocladium geodes and Cordyceps cicadae might be used in
      acetochlor bioremediation with a significant acetochlor, COD, TOC and BOD5
      reduction and can be used for rehabilitation of agricultural fields or receiving
      environments for removal the opposite effects of acetochlor or other herbicides.

PMID- 29368302
TI  - The Influence of Six Pesticides on Physiological Indices of Pelophylax Ridibundus
      (Pallas, 1771).
AB  - The objective of the study is to screen for morphological, biochemical and
      histological changes induced by six widely used pesticides (Reldan 40EC, Actara
      25WG, Tilt 250EC, Champion 50WG, Fusilade Forte, Dual Gold 960EC) in the
      amphibian species Pelophylax ridibundus (Pallas, 1771). Highly degenerative
      changes were observed in animals cultured at 22-24 degrees C, compared to those
      cultured at 4-6 degrees C. The hepatosomatic index increased upon exposure to
      almost all of the pesticides, the erythrocyte number decreased upon exposure to
      all pesticides except Reldan 40EC, while leucopenia was observed only for Reldan
      40EC and Actara 25WG. Hyperglycemia was observed upon administration of
      pesticides (except Champion 50WG and Fusilade Forte, for which hypoglycemia is
      registered), while a decrease in cholesterol levels was induced by nearly all
      pesticides. Triglycerides varied only slightly. The results suggest that chronic
      pesticides exposure can lead to alteration of various indices, as well as to
      hepatic lesions in amphibians.

PMID- 29368303
TI  - Determination of Domoic Acid in Plankton Net Samples from Golden Horn Estuary,
      Turkey, Using HPLC with Fluorescence Detection.
AB  - This study focused on the fluctuations of domoic acid (DA) levels in plankton net
      samples collected from the Golden Horn Estuary (GHE), Turkey, between August 2011
      and July 2012. DA concentrations were determined by high-performance liquid
      chromatography (HPLC), using a fluorenylmethoxycarbonyl (FMOC) derivatization
      technique. Monthly and biweekly data were evaluated with environmental variables,
      and their influence on DA production is discussed. DA levels in plankton net
      samples varied between 0.36 and 94.34 ug L- 1. DA levels showed remarkable
      seasonal variation and they were generally higher in May, 2012, but no DA was
      detected between February and April, 2012. DA production was mostly controlled by
      temperature, with nitrate and silicate limitations being secondary factors that
      influenced DA concentrations.

PMID- 29368304
TI  - Levels of PCDD/Fs, PBDEs, and PBDD/Fs in Breast Milk from Southern Taiwan.
AB  - This study investigates the congener-specific concentrations of polychlorinated
      dibenzo-p-dioxins/furans (PCDD/Fs), polybrominated dibenzo-p-dioxins/furans
      (PBDD/Fs), and polybrominated diphenyl ethers (PBDEs) in 25 breast milk samples
      from southern Taiwan. Most investigated congeners in Taiwanese breast milk are
      detectable except for PBDD/Fs. The geometric means of PCDD/Fs and PBDEs in the
      breast milk are 2.44 pg WHO2005-TEQ/g lipid and 2810 pg/g lipid. Several PCDD/F
      and PBDE congeners were highly correlated to each other like 1,2,3,7,8-PeCDD and
      2,3,4,7,8-PeCDF (r = 0.919, p < 0.001). The longest duration of menstruation
      could be predicted by BDE-153 (beta = 0.252) and 1,2,3,4,6,7,8-HpCDF (beta =
      0.345) with adjustment of confounders using a multiple stepwise linear regression
      model (r = 0.963, p < 0.001).

PMID- 29368305
TI  - Theodor Kerckring (1638-1693) and his contributions to describing fetal
      development and craniospinal malformations.

PMID- 29368306
TI  - Surgical treatment of a type IV cystic sacrococcygeal teratoma with intraspinal
      extension utilizing a posterior-anterior-posterior approach: a case report.
AB  - Type IV sacrococcygeal teratoma with intraspinal involvement is rare and to our
      knowledge has not been reported previously in the literature. The authors present
      the case of a 2-month-old infant with a type IV sacrococcygeal teratoma diagnosed
      on prenatal ultrasound. Postnatal MRI revealed intraspinal extension through an
      enlarged sacral neuroforamina on the right side. On surgical exploration, the
      authors discovered a dorsal cystic tumor involving the sacral spine that extended
      through an enlarged S4 foramen to a large presacral component. The tumor was
      successfully removed to achieve a complete en bloc surgical resection. The
      authors review the epidemiology, pathophysiology, and treatment of sacrococcygeal
      teratomas with intraspinal extension.

PMID- 29368307
TI  - Hashimoto's encephalopathy presenting as pseudobulbar palsy.
AB  - INTRODUCTION: Hashimoto's encephalopathy (HE) is an autoimmune condition with
      varied neurological and psychiatric features. HE is very unusual as a cause of
      pseudobulbar palsy (PSP). CASE PRESENTATION: A 14-year-old male was admitted with
      right-sided weakness, dysphagia, speech disorder, and aggressiveness. Brain
      magnetic resonance imaging showed increased intensity in bilateral temporal,
      insular cortex, amygdala, and parahippocampal area on T2-weighted and fluid
      attenuated inversion recovery images. Autoimmune encephalitis was considered as
      the patient had subacute onset of psychiatric and motor disturbances with normal
      findings for cerebrospinal fluid. N-methyl-D-aspartate receptor, anti-glutamate
      type alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1 and 2, anti
      contactin-associated protein-like 2, anti-gamma-aminobutyric acid receptor, anti
      Leucine-rich, and glioma-inactivated 1 antibodies were negative but the anti
      thyroperoxidase (antiTPO) level was greater than 998 IU/ML (n:0-9). Steroid
      therapy was initiated as pulse therapy and maintained with 2-mg/kg/day dose with
      the diagnosis of HE. He was symptom free for 6 months. In the follow-up period,
      he had two recurrences which responded to steroid therapy. CONCLUSION: The common
      causes of PSP are demyelinating, vascular, and motor neuron diseases and
      congenital malformations of the opercular or insular cortex. However, there are
      no cases of PSP developing after any autoimmune encephalitis. This case
      highlights the importance of early detection of antiTPO antibodies with the
      findings of PSP due to autoimmune encephalitis.

PMID- 29368309
TI  - Are we treating osteoporotic fractures of the hip adequately? A Middle Eastern
      cohort study.
AB  - : Fragility hip fractures treated in a center in the Middle East were
      retrospectively studied for adequacy of osteoporosis management. Of the 318
      patients treated, over 70% did not have a structured investigation and about 30%
      did not receive any therapeutic supplements. Our series showed a preventable 8.8%
      secondary fracture rate. PURPOSE: To study the adequacy of evaluation and
      treatment of osteoporosis after fragility fractures of the hip. The study also
      attempts to estimate the prevalence of secondary fractures after the original
      injury. METHODS: This is a retrospective evaluation of the electronic database to
      search all the admissions for fractures of the hip in patients over 50 years at a
      tertiary care Trauma and Orthopaedic center in the Sultanate of Oman. The study
      period was defined as October 2010 to December 2015. Their case records, BMD
      reports, and laboratory data were analyzed. Pharmacological interventions and the
      documented compliance with such therapy were also recorded. RESULTS: Over the
      study period, 318 fragility fractures of the hip were treated. Of these, 233
      (73.3%) did not receive a DEXA scan and 94% did not have their vitamin D3 (vit D)
      tested. About 29.9% percent cases did not receive any nutritional supplement or
      therapeutic intervention though diagnosed as fragility fracture. Twenty-eight
      patients (8.8%) reported for secondary fractures of the hip. Of these, 86% was
      initiated on supplement after their index fracture though 78.6% had not had a BMD
      study. CONCLUSIONS: Less than 27% patients receive BMD test following fragility
      fracture of the hip and only 6% a vit D3 assay. Secondary fractures of the hip
      tend to occur in approximately 9% of the cases in Oman; this seems to occur
      equally in patients who have had as well as not had any calcium and vit D
      supplements after the index injury.

PMID- 29368310
TI  - Trajectories of quality of life following breast cancer diagnosis.
AB  - PURPOSE: Although quality of life (QoL) improves over time for most breast cancer
      survivors (BCS), BCS may show different patterns of QoL. This study sought to
      identify distinct QoL trajectories among BCS and to examine characteristics
      associated with trajectory group membership. METHODS: BCS (N = 653) completed
      baseline assessments within 8 months of diagnosis. QoL was assessed by the
      Functional Assessment of Cancer Therapy-Breast (FACT-B) at baseline and 6, 12,
      and 18 months later. Finite mixture modeling was used to determine QoL
      trajectories of the trial outcome index (TOI; a composite of physical well-being,
      functional well-being, and breast cancer-specific subscales) and emotional and
      social/family well-being subscales. Chi-square tests and F tests were used to
      examine group differences in demographic, cancer-related, and psychosocial
      variables. RESULTS: Unique trajectories were identified for all three subscales.
      Within each subscale, the majority of BCS had consistently medium or high QoL.
      The TOI analysis revealed only stable or improving groups, but the emotional and
      social/family subscales had groups that were stable, improved, or declined.
      Across all subscales, women in "consistently high" groups had the most favorable
      psychosocial characteristics. For the TOI and emotional subscales, psychosocial
      variables also differed significantly between women who started similarly but had
      differing trajectories. CONCLUSIONS: The majority of BCS report good QoL as they
      transition from treatment to survivorship. However, some women have persistently
      low QoL in each domain and some experience declines in emotional and/or
      social/family well-being. Psychosocial variables are consistently associated with
      improving and/or declining trajectories of physical/functional and emotional well
      being.

PMID- 29368312
TI  - The Role of Bundle Size for Preventing Surgical Site Infections after Colorectal
      Surgery: Is More Better?

PMID- 29368311
TI  - Impact of chemotherapy relative dose intensity on cause-specific and overall
      survival for stage I-III breast cancer: ER+/PR+, HER2- vs. triple-negative.
AB  - PURPOSE: To investigate the impact of chemotherapy relative dose intensity (RDI)
      on cause-specific and overall survival for stage I-III breast cancer: estrogen
      receptor or progesterone receptor positive, human epidermal-growth factor
      receptor negative (ER+/PR+ and HER2-) vs. triple-negative (TNBC) and to identify
      the optimal RDI cut-off points in these two patient populations. METHODS: Data
      were collected by the Louisiana Tumor Registry for two CDC-funded projects. Women
      diagnosed with stage I-III ER+/PR+, HER2- breast cancer, or TNBC in 2011 with
      complete information on RDI were included. Five RDI cut-off points (95, 90, 85,
      80, and 75%) were evaluated on cause-specific and overall survival, adjusting for
      multiple demographic variables, tumor characteristics, comorbidity, use of
      granulocyte-growth factor/cytokines, chemotherapy delay, chemotherapy regimens,
      and use of hormone therapy. Cox proportional hazards models and Kaplan-Meier
      survival curves were estimated and adjusted by stabilized inverse probability
      treatment weighting (IPTW) of propensity score. RESULTS: Of 494 ER+/PR+, HER2-
      patients and 180 TNBC patients, RDI < 85% accounted for 30.4 and 27.8%,
      respectively. Among ER+/PR+, HER2- patients, 85% was the only cut-off point at
      which the low RDI was significantly associated with worse overall survival (HR =
      1.93; 95% CI 1.09-3.40). Among TNBC patients, 75% was the cut-off point at which
      the high RDI was associated with better cause-specific (HR = 2.64; 95% CI 1.09,
      6.38) and overall survival (HR = 2.39; 95% CI 1.04-5.51). CONCLUSIONS: Higher RDI
      of chemotherapy is associated with better survival for ER+/PR+, HER2- patients
      and TNBC patients. To optimize survival benefits, RDI should be maintained >= 85%
      in ER+/PR+, HER2- patients, and >= 75% in TNBC patients.

PMID- 29368313
TI  - The use of point-of-care ultrasound to diagnose patent foramen ovale in elective
      hip and knee arthroplasty patients and its association with postoperative
      delirium.
AB  - PURPOSE: Hip and knee arthroplasty surgeries are associated with embolism of
      materials such as air, cement, and fat. Patent foramen ovale (PFO) is a common
      congenital cardiac condition that has been reported to lead to paradoxical
      embolism. This observational study aimed to investigate if the presence of a PFO
      was associated with an increased risk of postoperative delirium in patients
      undergoing primary elective hip or knee arthroplasties. METHOD: This was a
      prospective cohort study at a tertiary teaching hospital. We enrolled patients
      undergoing primary elective hip or knee arthroplasty who did not have any risk
      factors for embolism or delirium. Bedside transthoracic echocardiography (TTE)
      with a bubble study was performed on all patients to detect the presence of PFO.
      The primary outcome was postoperative delirium as assessed by the standardized
      Confusion Assessment Method. Secondary outcomes included the ease of performing a
      TTE bubble study in the perioperative setting, the quality of the TTE images,
      length of stay, major cardiovascular and neurologic complications, and effects of
      anesthetic or analgesic management techniques on delirium. RESULTS: Two hundred
      two patients completed the study. The median [interquartile range] duration of
      stay was 2 [2-3] days. Only 16 patients (8%) had a positive bubble study.
      Postoperative delirium was observed in only one patient. Major adverse events
      were not seen. The inter-rater reliability for the TTE image quality scores was
      fair (kappa statistic = 0.22). CONCLUSION: Given the very low incidence of PFO
      and postoperative delirium in this study, we could not form any conclusions
      regarding the impact of a PFO on important outcomes including delirium or other
      major adverse events. No recommendation can be made regarding screening for PFO
      in patients scheduled for lower extremity arthroplasty surgery. TRIAL
      REGISTRATION: ClinicalTrials.gov (NCT02400892). Registered 27 March 2015.

PMID- 29368314
TI  - Avoidable tracheal injury using a double-lumen endotracheal tube: a case report.

PMID- 29368315
TI  - Intraoperative Valsalva maneuver: a narrative review.
AB  - The Valsalva maneuver (VM) involves expiratory effort against a closed mouth
      and/or glottis in the sitting or supine position with the increased intraoral and
      intrathoracic pressure raised to 40 mmHg for 15-20 sec after which the pressure
      is suddenly released and the breathing restored to normal. Complex cardiovascular
      and other physiologic changes occur during the VM. The VM has been used for
      diagnostic and therapeutic reasons as well as intraoperatively during specific
      surgical procedures. Although the VM is usually safe, rare complications have
      been reported. This review examines the published literature surrounding the VM
      and explores the physiologic changes that occur during its performance. Attempts
      have been made to understand its intraoperative uses and complications and how
      these can be prevented.

PMID- 29368316
TI  - Comparison of Sinonasal Complications of Microscopic and Endoscopic Approaches
      for Transsphenoidal Hypophyseal Surgery: Prospective Study.
AB  - AIM: To compare sinonasal complications after microscopic and endoscopic
      approaches for pituitary adenomas. MATERIAL AND METHODS: At our clinic, sinonasal
      complications occurred in 31 patients who underwent microscopic transsphenoidal
      surgery between 2007 and 2014 and in 32 patients who underwent endoscopic
      transsphenoidal surgery between 2014 and 2016. We statistically compared the
      complications observed during endoscopic sinonasal examination performed by an
      otorhinolaryngologist. RESULTS: Sinonasal pathology occurred in 22 of the 31
      patients (70.9%) in the microscopy group (Group 1) and 19 of the 32 (59.3%) in
      the endoscopy group (Group 2). Of the 31 patients in Group 1, 13 had nasal septal
      perforation, 13 had nasal synechiae, three had anosmia, two had hyposmia and one
      had saddle nose deformity. In Group 2, no patient had nasal septal perforation,
      whereas eight had nasal synechiae, one had anosmia, 11 had hyposmia, and 4 had
      infection. CONCLUSION: There were no statistically significant differences in
      sinonasal complications (e.g. synechiae, anosmia, deformity, and sinusitis)
      between the two groups. Although the perforation rate (especially for
      perforations in the middle portion of the septum) was statistically greater in
      Group 1 than in Group 2, the hyposmia rate was statistically greater in Group 2
      than in Group 1.

PMID- 29368317
TI  - Modified Frailty Index and Body Mass Index as Predictors of Adverse Surgical
      Outcomes in Degenerative Spinal Disease.
AB  - AIM: To reveal the potential relationships and interactive effects between
      frailty and body weight and adverse surgical outcomes for degenerative spinal
      disease. MATERIAL AND METHODS: Patients who underwent open surgery for
      degenerative spinal disease in our hospital were included. Data on the patients
      and disease variables was obtained. The primary independent variables included
      body mass index (BMI) and modified Frailty Index (mFI). The primary outcome was
      the Clavien-Dindo complications classification. After univariate analyses,
      multinomial and ordinal regression analyses were applied with the Clavien-Dindo
      complications grade as the dependent variable and the potential risk factors for
      complications as independent variables, respectively, to determine the potential
      interactive relationship between the two primary risk factors and their impact on
      postoperative complications grading. RESULTS: A total of 1970 patients were
      included in the study. The results showed that "underweight" could significantly
      increase the odds ratios of "prefrail" and "frail" at the same time; however,
      "obese" could only increase the odds ratio of "frail". The "underweight",
      "obese", "prefrail" and "frail" subgroups could significantly increase the
      grading of postoperative complications, respectively. If mFI and BMI were
      combined as an interactive variable, the results showed that in the "underweight"
      and "normal weight" subgroups, both "prefrail" and "frail" could significantly
      increase the grading of postoperative complications; however, in the "overweight"
      and "obese" subgroups, only the "overweight/frail", "obese/non-frail" and
      "obese/frail" subgroups displayed significantly increased grading of
      postoperative complications. CONCLUSION: The present results serve to stratify
      susceptible patients with easily identified risk factors preoperatively.

PMID- 29368318
TI  - Effects of Resveratrol on Inflammation and Apoptosis After Experimental Spinal
      Cord Injury.
AB  - AIM: To determine the effects of resveratrol on inflammation and apoptosis after
      experimental spinal cord injury (SCI). MATERIAL AND METHODS: Eighteen Sprague
      Dawley rats were randomly divided into three groups. All groups underwent
      thoracic laminectomy. The first group received no other intervention. The second
      and third groups suffered SCI via the aneurysm clip compression method, and
      additionally the third group received resveratrol. After euthanizing the rats,
      immunohistochemical analysis and biochemical parameters of tumor necrosis factor
      alpha (TNF-?) and interleukin (IL)-1? were measured. RESULTS: The resveratrol
      group had statistically significant lower levels of TNF-?, IL -1?, and terminal
      deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) positive
      cells and higher number of glial and motor neuron cells. CONCLUSION: Resveratrol
      proves to have remarkable neuroprotective effects on SCI in an experimental model
      in addition to its proven cardioprotective effects.

PMID- 29368319
TI  - Is Implant Washing and Wound Irrigation with Rifampicin Effective for Preventing
      Surgical Site Infections in Lumbar Instrumentation?
AB  - AIM: To determine whether the washing of implants and autogenous bone grafts with
      rifampicin, and the irrigation of the surgical field using diluted rifampicin,
      have any significant effect on the prevention of spinal implant infections.
      MATERIAL AND METHODS: A total of 166 consecutive lumbar stenosis and
      spondylolisthesis patients undergoing lumbar instrumentation between 2012 and
      2016 were analyzed retrospectively. The patients were divided into two groups.
      Group I (n=85) included patients whose implants were washed with rifampicin
      immediately before insertion and whose surgical fields were irrigated with
      diluted rifampicin immediately after insertion. Group II (n=81) included the
      cases without rifampicin application. Both groups were matched for age, sex, body
      mass index, and surgical indication. The infection rates of the groups were
      compared during the first 2 postoperative years. RESULTS: No significant
      difference was found between the infection rate in Group I and Group II. Only 1
      case had surgical site infection (SSI) in Group I, a rate of 1.17% (1 of 85
      patients), whereas 2 patients had SSI in Group II, a rate of 2.46% (2 of 81
      patients). CONCLUSION: Peroperative washing of implants with rifampicin and
      irrigation of the surgical field using diluted rifampicin have not been found to
      be significantly effective in preventing or reducing spinal implant infections.
      However, further studies with larger series need to be carried out to verify
      these results.

PMID- 29368320
TI  - Expression of Nestin, CD133 and Sox2 in Meningiomas.
AB  - AIM: To investigate the expression of cancer stem cell markers in meningiomas.
      MATERIAL AND METHODS: CD133, Nestin and Sox2 expression levels in 35 paraffin
      embedded meningioma tissue samples were assessed using immunohistochemistry.
      RESULTS: In this study, five cases were atypical (WHO Grade II), two were
      anaplastic (WHO Grade III), and 28 were benign (WHO Grade I). Among atypical and
      anaplastic meningiomas, all were positive for Nestin and CD133, and 4 were
      positive for Sox2. Of the 28 benign meningiomas, 23 were positive for Nestin, 11
      were positive for CD133, and none were positive for Sox2. In addition, Nestin and
      CD133 were expressed at significantly higher levels in the non-benign group than
      in the benign group. CONCLUSION: Nestin, CD133 and Sox2 expression levels may be
      correlated with the WHO pathological grade. Specifically, more aggressive
      meningiomas are characterized by higher positivity rates and higher levels of
      Nestin, CD133 and Sox2 expression in positive cells.

PMID- 29368321
TI  - Radiation-Induced Meningiomas: A Series of Consecutive Four Patients and Review
      of the Literature.
AB  - AIM: To assess the clinical outcomes of treatment for radiation-induced
      meningiomas. MATERIAL AND METHODS: Medical records of all cranial meningioma
      cases which diagnosed or/and underwent surgery in our hospital, during a 7-year
      period from 2009 to 2016 were retrospectively reviewed. All radiation-associated
      meningiomas were selected as the core sample used for this study. RESULTS: This
      series included one female and three male patients with mean age 47.3+/-16.3
      years on average. The mean preoperative course was less than three months. The
      most common presenting symptom was headache (100%). Three patients had alopecia
      and thin scalp skin. The mean age when received radiotherapy was 18.5+/-13.7. The
      mean latency period was 19.2+/-7.4 years. The first malignancies were two
      desmoplastic medulloblastomas (13-year-old female, 65Gy), (11-year-old male,
      54Gy) and one oligodendroglioma-gradeII (39-year-old male, 30Gy). One patient
      received radiotherapy for chronic otitis (10-year-old male, Low-dose). The
      histopathological examinations were revealed (fibroblastic-gradeI, Ki-67 was 2
      3%, 25.5years, cerebellopontine angle), (atypical meningioma-gradeII, ki-67 was
      8%, 21years, frontal) and (transitional-gradeI, ki-67 was 3-4%, 11years,
      frontal), respectively. Fourth patient had three radiation-induced meningiomas
      and 27 radiation-induced cavernomas. This patient had treated using gamma knife.
      The mean follow-up period was 34.8+/-39.4 months. One patient had rhinorrhea,
      another one was experienced CSF fistula. Both of them were re-operated. The
      former was lost after involved with meningitis on postoperative 31st day.
      CONCLUSION: Most radiation-induced meningiomas are low-grade, but they have high
      trend to recurrence. Close follow-up and yearly MRI would minimize their
      morbidity rate. To reduce fatal complications, surgery has to plan with plastic
      surgeons.

PMID- 29368322
TI  - Variation and Anomalies of the Posterior Cerebral Artery: Review and Pilot Study.
AB  - Variations and anomalies of the posterior cerebral artery (PCA) have several
      clinical implications, including assisting in understanding the clinical signs of
      a stroke. Anomalies have been described previously; however, few reports mention
      the origins, absence, duplication and triplication of the cortical branches.
      Furthermore, the PCA branching pattern has not been adequately described. The aim
      of this study is to describe the anatomy and anomalies of the PCA. Results of a
      pilot study were additionally included. The quantity, origin, diameter and length
      of the PCA cortical branches were described in this review, as well as the
      branching pattern and the anomalies. Accordingly, the pilot study reported on
      these aspects. In the pilot study it was evident that the description of the
      branching pattern is not the "normal" pattern, since it was only observed in one
      case. This pattern was re-evaluated and three groups were described;
      monofurcation, bifurcation and trifurcation. Furthermore, one case of a
      fenestration was observed. Aneurysms tend to form at branching points, thus
      knowledge of the branching pattern can aid in detection of ruptured and un
      ruptured aneurysms in this region. This review outlined several gaps in the
      literature, and a pilot study was included to fill some of these gaps. Future
      research should especially focus on the branching pattern of the PCA. Possible
      sex, age and population differences may also exist.

PMID- 29368323
TI  - Development of a giant cornu cutaneum in a patient with a coincidental foreknown
      intracranial meningioma.
AB  - The diagnostic spectrum for scalp lesions is extensive and comprises either
      benign or malignant features. Cornu cutaneum (CC) is a well-recognized condition;
      however, its origin and natural course are not always obvious. We present the
      case of a 78-year-old patient who was diagnosed with intracranial meningioma in
      2014 and who subsequently refused treatment. He presented a new scalp lesion,
      resembling a horn, in the vertex region 1.5 years after his last follow-up. The
      lesion was excised, and the patient was histopathologically diagnosed as having
      CC caused by squamous cell carcinoma. CC can be easily recognized when it
      resembles animal horn; however, it can assume different shapes that require a
      physician to be vigilant. Moreover, a lesion's benign or malignant nature is not
      obvious in all cases. Hard, protruding scalp lesions should be examined for CC,
      and a histopathological evaluation should be performed to make a definitive
      diagnosis.

PMID- 29368324
TI  - How to Reduce Stress on the Pedicle Screws In Thoracic Spine? Importance of Screw
      Trajectory: A Finite Element Analysis.
AB  - AIM: With wide application of the pedicle screw, clinical concerns have focused
      on accurate placement of the screws. Anatomic trajectory (AT) and straightforward
      trajectory (ST) are two popular techniques of pedicle screw insertion. Herein, we
      investigated the biomechanical comparison of thoracic transpedicular screw
      trajectories on the sagittal plane. To the best of our knowledge, this is the
      first comparative finite element analysis (FEA) on the different insertion
      trajectories of the pedicle screws in the thoracic spine. MATERIAL AND METHODS: A
      three-dimensional, nonlinear FEA model of T8 through T9 was used. AT and ST
      models of the transpedicular screws were used in the intact FEA model. The von
      Mises stress and range of motion (ROM) of the transpedicular screws were
      evaluated. RESULTS: The difference in ROM between both techniques was negligible.
      In lateral bending and axial rotation, FEA showed decrease in stress by 25% and
      8%, respectively, when pedicle screws were placed using AT. CONCLUSION: AT
      decreased the von-Mises stress of the pedicle screws, thereby reducing the rates
      of screw breakage and fatigue risks. In addition, we believe that AT could
      protect against screw loosening because the von-Mises stress of the internal
      fixation was scattered.

PMID- 29368325
TI  - [Effectiveness of virtual immersion programmes in patients with Parkinson's
      disease. A systematic review].
AB  - INTRODUCTION: Parkinson disease (PD) is the second most common neurodegenerative
      disease. Virtual reality (VR) is being used in rehabilitation of neurological
      patients. To analyze the VR systems' therapeutically effectiveness through PD
      diagnosed subjects with variables of motor, quality of life and cognition.
      PATIENTS AND METHODS: Electronics database were used to look for articles:
      Medline, EMBASE, PEDro, CINAHL and Cochrane. The inclusion criteria were:
      randomized control trial (RCT) performed in PD with at least one VR variable
      included in the therapeutically treatment and diagnosed PD subjects. Four RCT
      were chosen showing all good methodology quality. Concordance between evaluators
      was moderate-high. VR was the main treatment in all of them. RESULTS: VR was more
      effective in balance improvement in PD subjects than conventional physiotherapy
      in two RCT. VR was not more effective in balance improvement in PD subjects than
      conventional physiotherapy in two RCT. Contradictory evidences where showed
      between the effectiveness of the VR programs versus conventional programs in the
      effectiveness of balance treatment with PD subjects. Non-motor variables
      improvement was not greater in subjects with VR treatments versus the ones with
      conventional physiotherapy in the four RCT. CONCLUSIONS: The treatments with VR
      cannot be assumed as more effectives than conventional physiotherapy through PD
      subjects in motor and psychosocial variables.

PMID- 29368326
TI  - [Spanish translation and validation of the neuromuscular module of the Pediatric
      Quality of Life Inventory (PedsQL): evaluation of the quality of life perceived
      by the parents of 2-4-year-old children with neuromuscular diseases].
AB  - INTRODUCTION: Paediatric neuromuscular disorders, which negatively impact on
      children's health-related quality of life (HRQoL), are a frequent cause of
      parental consultation with a physiotherapist. Parents' stress overload triggers a
      poor perception of their children's HRQoL. For this reason, it is essential to
      have psychometrically sound instrument to measure parent's perceptions such as
      the Pediatric Quality of Life Inventory (PedsQL) Neuromuscular Module. AIM: To
      assess the validity and reliability of the Spanish version of PedsQL
      Neuromuscular Module for parent perceived quality of life of children aged 2-4
      with neuromuscular disorders. SUBJECTS AND METHODS: The cognitive validity of the
      Spanish version of PedsQL was carried out with Mapi Research Trust permission.
      Subsequently, a test-retest was performed with 42 parent volunteers of children
      aged 2-4 with paediatric neuromuscular disorders. This allowed an evaluation of
      PedsQL intra-observer concordance and internal consistency. Finally, construct
      validity was evaluated through factor analysis. RESULTS: The Cronbach alpha and
      all correlation intra-observer coefficients were higher than 0.8, indicating
      excellent validity and reliability. The construct validity analysis presented
      63.5% variability and such analysis suggested that a seven-dimension construct
      might be a better fit than three. CONCLUSIONS: The Spanish version of PedsQL
      Neuromuscular Module for parent perceived quality of life of children aged 2-4
      presented excellent validity and reliability.

PMID- 29368327
TI  - [Neuropsychological alterations in narcolepsy with cataplexy: a review].
AB  - AIM: To describe the current state of the art about the main cognitive deficits
      that appear in patients affected with narcolepsy with cataplexy (NT1).
      DEVELOPMENT: The majority of the studies have found that the most impaired
      cognitive functions are attention (especially maintenance of attention or
      sustained attention), speed of information processing and executive functions (in
      particular, verbal fluency and resistance to the stimuli interference). These
      data indicate the difficulty to use the available cognitive resources of the
      patient. These alterations are similar to those present in other hypersomnias,
      although they might differ in intensity. Moreover, most of the studies emphasize
      a high prevalence of different depressive and anxious disorders. It has been
      suggested that predisposition to anxiety could be part of the characteristic
      phenotype of these patients. Anxiety could act either as a trigger for the
      disease or a consequence of the disease. CONCLUSIONS: Cognitive deficits in
      patients with NT1 appear in long lasting and/or monotonous tasks and in high
      cognitive demanding tasks. The presence of depressive symptomatology, together
      with excessive daytime sleepiness in these patients could affect their
      performance in neuropsychological test, and it might be related to their
      subjective perception of the cognitive deficits.

PMID- 29368328
TI  - ['The man with the withered hand': iconography of the saturnine palsy?]
AB  - INTRODUCTION: The synoptic gospels tell about a man who cannot extend his hand,
      that appeared dried. The description is consistent with radial palsy. Christian
      artists depicted this gospel story producing a rich material, unexplored from the
      medical point of view. AIM: To analyze the mentioned iconography verifying the
      depicted lesions and their possible causes. DEVELOPMENT: Six representations of
      the evangelical text pertaining to the period comprehended between 10th and 17th
      centuries were selected. Four belong to illuminated gospels, one is a mosaic and
      the other one is a fresco. In three of them the figure with the palsy hand
      appeared holding the affected member with the opposite hand; another one has a
      foot drop. The description of postures that are characteristic of extensor
      palsies points out that these artists must have known real patients. Saturnism,
      frequent in Europe during the period in which these works were created, was
      probably the cause of the paralysis in these cases. Another hypothesis was that
      the artists could have suffered themselves saturnism, caused by manipulating
      paints with high lead content; this could not be confirmed. CONCLUSIONS: The
      iconographies of 'the man with the withered hand' are realistic representations
      of motor paralysis consistent with saturnine neuropathy. These works preceded for
      a long time the best medical descriptions of such condition.

PMID- 29368329
TI  - [Hereditary primary microcephaly type 5. Not everything is Zika virus].

PMID- 29368330
TI  - Mortality Risk Along the Frailty Spectrum: Data from the National Health and
      Nutrition Examination Survey 1999 to 2004.
AB  - OBJECTIVES: To determine the relationship between frailty and overall and
      cardiovascular mortality. DESIGN: Longitudinal mortality analysis. SETTING:
      National Health and Nutrition Examination Survey (NHANES) 1999-2004.
      PARTICIPANTS: Community-dwelling older adults aged 60 and older (N = 4,984; mean
      age 71.1 +/- 0.19, 56% female). MEASUREMENTS: We used data from 1999-2004 cross
      sectional NHANES and mortality data from the National Death Index, updated
      through December 2011. An adapted version of Fried's frailty criteria was used
      (low body mass index, slow walking speed, weakness, exhaustion, low physical
      activity). Frailty was defined as persons meeting 3 or more criteria, prefrailty
      as meeting 1 or 2 criteria, and robust (reference) as not meeting any criteria.
      The primary outcome was to evaluate the association between frailty and overall
      and cardiovascular mortality. Cox proportional hazard models were used to
      evaluate the association between risk of death and frailty category adjusted for
      age, sex, race, smoking, education, coronary artery disease, heart failure,
      nonskin cancer, diabetes, and arthritis. RESULTS: Half (50.4%) of participants
      were classified as robust, 40.3% as prefrail, and 9.2% as frail. Fully adjusted
      models demonstrated that prefrail (hazard ratio (HR) = 1.64, 95% confidence
      interval (CI) = 1.45-1.85) and frail (HR = 2.79, 95% CI = 2.35-3.30) participants
      had a greater risk of death and of cardiovascular death (prefrail: HR = 1.84, 95%
      CI = 1.45-2.34; frail: HR = 3.39, 95% CI = 2.45-4.70). CONCLUSION: Frailty and
      prefrailty are associated with increased risk of death. Demonstrating the
      association between prefrail status and mortality is the first step to
      identifying potential targets of intervention in future studies.

PMID- 29368331
TI  - Intellectual developmental disorder with cardiac arrhythmia syndrome in a child
      with compound heterozygous GNB5 variants.
AB  - Identification of a novel compound heterozygous of GNB5 in a patient with
      intellectual developmental disorder with cardiac arrhytmia (IDDCA), from non
      consaguineous family. Three-dimensional modelling and in silico predictions
      suggest that GNB5 variants are causative of the phenotype, extending the number
      of IDDCA patients so far identified.

PMID- 29368332
TI  - Head and neck cancers associated with exposure to the September 11, 2001 World
      Trade Center terrorist attacks.
AB  - Exposure at the World Trade Center (WTC) terrorist collapse site on September 11,
      2001 has been associated with increased cancer risk, though observational studies
      have identified very few cases of head and neck cancer (HNC) in exposed
      individuals. Eighty seven patients were identified who presented to our
      institution with HNC diagnosed from 2002 to 2017 who reported WTC exposure. The
      annual number and proportion of WTC-exposed HNC patients has been steadily
      increasing since 2002, with most cancers developing >10 years following the
      event. Furthermore, WTC-exposed patients with human papillomavirus (HPV)-positive
      OPC experienced significantly inferior outcomes compared with non-WTC exposed
      patients with HPV+ OPC (disease free survival 80.1% vs. 65.6% at 4 years, p =
      0.04). This single institution study cannot establish evidence of exposure
      mediated causation but higher recurrence rates in the WTC-exposed HPV+ OPC
      population suggest a treatment refractory tumor biology and possible exposure
      synergism with HPV-mediated oncogenesis.

PMID- 29368333
TI  - Corrigendum.

PMID- 29368334
TI  - Medical Schools in Fragile States: Implications for Delivery of Care.
AB  - OBJECTIVE: To report on medical schools in fragile states, countries with severe
      development challenges, and the impact on the workforce for health care delivery.
      DATA SOURCES: 2007 and 2012 World Bank Harmonized List of Fragile Situations;
      1998-2012 WHO Global Health Observatory; 2014 World Directory of Medical Schools.
      DATA EXTRACTION: Fragile classification established from 2007 and 2012 World Bank
      status. Population, gross national income, health expenditure, and life
      expectancy were 2007 figures. Physician density was most recently available from
      WHO Global Health Observatory (1998-2012), with number of medical schools from
      2014 World Directory of Medical Schools. STUDY DESIGN: Regression analyses
      assessed impact of fragile state status in 2012 on the number of medical schools
      in 2014. PRINCIPAL FINDINGS: Fragile states were 1.76 (95 percent CI 1.07-2.45)
      to 2.37 (95 percent CI 1.44-3.30) times more likely to have fewer than two
      medical schools than nonfragile states. CONCLUSIONS: Fragile states lack the
      infrastructure to train sufficient numbers of medical professionals to meet their
      population health needs.

PMID- 29368335
TI  - Morphine and pholcodine-specific IgE have limited utility in the diagnosis of
      anaphylaxis to benzylisoquinolines.
AB  - BACKGROUND: Investigation of immediate hypersensitivity reactions in the
      perioperative setting involves skin testing and measurement of specific IgE
      (sIgE) as standard practice. In the case of the neuromuscular blocking agents
      (NMBAs), the main allergenic epitopes have been shown to be substituted ammonium
      groups. Commercial assays are available for detection of sIgE to these epitopes
      using morphine and pholcodine substrates but questions have been raised about the
      effectiveness of these assays in the diagnosis of benzylisoquinoline anaphylaxis.
      This study was therefore undertaken to assess the effectiveness of these assays
      in the diagnosis of hypersensitivity reactions to this group of NMBAs. METHODS:
      Analysis was carried out on all available results for patients assessed at the
      Royal North Shore Hospital Anaesthetic Allergy Clinic during the period June 2009
      to June 2016. Standardised intradermal skin tests were performed with a panel of
      NMBAs. Measurement of sIgE to morphine and pholcodine was performed via the
      Phadia ImmunoCAP(r) system. RESULTS: For all patients with positive skin test
      results to NMBAs which included a benzylisoquinoline NMBA (n = 24), 75% exhibited
      negative sIgE to both morphine and pholcodine. Where patients were reactive to
      benzylisoquinoline NMBAs alone (n = 12), 100% exhibited negative sIgE results,
      indicating 0% sensitivity of the assays relative to skin testing, in this
      subgroup. CONCLUSION: Use of sIgE testing to morphine and pholcodine in the
      assessment of NMBA immediate hypersensitivity is a valuable tool particularly in
      the case of reactions to the aminosteroid NMBAs. However, these assays are
      unreliable in detecting sensitisation to benzylisoquinoline NMBAs.

PMID- 29368336
TI  - Pulsed-dye laser therapy for carcinoma in situ of the penis.

PMID- 29368337
TI  - A profile of Propionibacterium acnes resistance and sensitivity at a tertiary
      dermatological centre in Singapore.

PMID- 29368338
TI  - Quantitative proteomics reveals that miR-222 inhibits erythroid differentiation
      by targeting BLVRA and CRKL.
AB  - miR-222 plays an important role in erythroid differentiation, but the potential
      targets of miR-222 in the regulation of erythroid differentiation remain to be
      determined. The target genes of miR-222 were identified by proteomics combined
      with bioinformatics analysis in this study. Thirteen proteins were upregulated,
      and 13 were downregulated in K562 cells following transfection with miR-222
      inhibitor for 24 and 48 hours. Among these proteins, BLVRA and CRKL were
      upregulated after transfection of miR-222 inhibitor in K562 cells and human CD34+
      HPCs. Moreover, miR-222 mimics reduced and miR-222 inhibitor enhanced the mRNA
      and protein levels of both BLVRA and CRKL. Luciferase assay showed that miR-222
      directly targeted 3'-UTR of BLVRA and CRKL. In addition, overexpression of either
      BLVRA or CRKL or both increased the erythroid differentiation of K562 cells,
      while silencing of either BLVRA or CRKL or both by siRNA significantly attenuated
      hemin-induced erythroid differentiation of K562 cells. Our results indicated that
      BLVRA and CRKL are targets of miR-222.

PMID- 29368340
TI  - Serum irisin concentrations in lean adolescents with polycystic ovary syndrome.
AB  - OBJECTIVE: To explore differences in irisin concentrations between lean
      adolescents with PCOS and age- and body mass index (BMI)-matched controls and
      examine the associations of irisin with core features of the syndrome. DESIGN:
      Cross-sectional study. PATIENTS: Lean females with PCOS, aged 13-21 years.
      MEASUREMENTS: Physical, hormonal and sonographic assessment. Irisin
      concentrations were measured with ELISA. RESULTS: Participants included in total
      39 sedentary females (mean +/- SD; age 17.3 +/- 2.1 years, BMI 20.7 +/- 1.3 Kg/m2
      ), 23 adolescents with PCOS and 16 controls. Adolescents with PCOS compared to
      controls had significantly elevated concentrations of fasting serum irisin (mean
      +/- SD; PCOS, 1.7 +/- 1.0 MUg/mL vs controls, 1.0 +/- 0.4 MUg/mL; P = .007),
      luteinizing hormone (LH), oestradiol, testosterone, Delta4-androstenedione, 17
      hydroxyprogesterone, glucose, as well as free androgen index, Ferriman-Gallwey
      score and mean ovarian volume (MOV). For the total sample, circulating irisin was
      positively correlated with MOV (r = .332, P = .041), glucose (r = .428, P =
      .007), insulin (rs  = .369, P = .021) and HOMA-IR (rs  = .422, P = .007) and
      negatively correlated with QUICKI (r = -.329, P = .041). Follicle-stimulating
      hormone (B = 0.295, Beta = .342, P = .042) and MOV (B = 0.182, Beta = 0.821, P =
      .001) were positive predictors, and LH (B = -0.108, Beta = -0.523, P = .010) and
      testosterone (B = -0.431, Beta = -0.457, P = .032) were negative predictors of
      irisin concentrations, whereas irisin positively predicted fasting glucose (B =
      0.262, Beta = 0.428, P = .007). In the PCOS group, irisin concentrations were
      positively correlated with HOMA-IR (rs  = .416, P = .048) but negatively
      correlated with LH (rs  = -.499, P = .015), testosterone (r = -.585, P = .003),
      free androgen index (r = -.426, P = .048) and Ferriman-Gallwey score (r = -.533,
      P = .015). CONCLUSIONS: Irisin was associated with the adolescents' metabolic and
      reproductive characteristics and the hyperandrogenic phenotype of the syndrome.
      Much research is needed to ascertain mechanisms of elevated serum irisin in
      adolescent PCOS.

PMID- 29368339
TI  - Anatomical localization and clinical impact of sentinel lymph nodes based on
      patterns of pelvic lymphatic drainage in clinically localized prostate cancer.
AB  - BACKGROUND: Although sentinel lymph node in prostate has been generating renewed
      interest, its significance remains controversial due to inadequate evidence.
      METHODS: We reviewed a prospective cohort of 50 consecutive patients with
      intermediate- to high-risk localized prostate cancer who had undergone
      laparoscopic radical prostatectomy. Sentinel lymph node biopsy by fluorescence
      detection using intraoperative imaging with indocyanine green and backup extended
      pelvic lymph node dissection were conducted prior to prostatectomy.
      Intraoperative and pathological findings were elaborated and compared for
      confirmation. RESULTS: Sentinel lymph nodes were successfully identified in 47
      patients (94%). A median of four sentinel lymph nodes was detected per patient.
      Lymph node metastasis was confirmed in six patients (12%), all of whom had
      positive sentinel lymph nodes. Three typical pathways of lymphatic drainage
      related to sentinel lymph nodes from the prostate were recognized. Ninety-one
      percent of the positive sentinel lymph nodes (10/11) were located at two
      predominant sites along these characteristic lymphatic pathways. One site was the
      junctional nodes, located at the junction between internal and external iliac
      vessels. The other was the distal internal iliac nodes, located along the
      inferior vesical artery. CONCLUSIONS: Over 90% of positive sentinel lymph nodes
      were identified at two predominant sites. Priority should be given to the removal
      of these sentinel lymph nodes, which are located closer to the prostate, in
      pelvic lymph node dissection. Particular attention should be paid to identifying
      these nodes to reduce the possibility of overlooking lymph node metastasis.

PMID- 29368341
TI  - Intraductal/ductal histology and lymphovascular invasion are associated with
      germline DNA-repair gene mutations in prostate cancer.
AB  - BACKGROUND: Germline mutations in genes mediating DNA repair are common in men
      with recurrent and advanced prostate cancer, and their presence may alter
      prognosis and management. We aimed to define pathological and clinical
      characteristics associated with germline DNA-repair gene mutations, to facilitate
      selection of patients for germline testing. METHODS: We retrospectively evaluated
      150 unselected patients with recurrent or metastatic prostate cancer who were
      offered germline genetic testing by a single oncologist using a clinical-grade
      assay (Color Genomics). This platform utilizes next-generation sequencing from
      saliva to interrogate 30 cancer-susceptibility genes. Presence or absence of a
      deleterious germline mutation was correlated with histological and clinical
      characteristics, and with family history of cancer. All patients with DNA
      sequence alterations (pathogenic or variants) were offered genetic counseling.
      RESULTS: Between July 2016 and July 2017, 150 consecutive patients underwent
      germline testing; pathogenic mutations were identified in 21 men (14%). Among
      those with germline mutations, 9 (43%) were in BRCA2, 3 (14%) were in ATM, 3
      (14%) were in CHEK2, and 2 (9%) were in BRCA1. While there were no associations
      between germline mutations and age, tumor stage, Gleason sum or family history;
      mutation-positive patients had lower median PSA levels at diagnosis (5.5 vs 8.6
      ng/mL, P = 0.01) and unique pathologic features. Namely, men with germline
      mutations were more likely to harbor intraductal/ductal histology (48% vs 12%, P
      < 0.01) and lymphovascular invasion (52% vs 14%, P < 0.01). Finally, 44% of
      patients with a positive germline test would not have been offered genetic
      screening according to current National Comprehensive Cancer Network (NCCN)
      guidelines. CONCLUSIONS: Presence of intraductal/ductal histology and
      lymphovascular invasion appear to be associated with pathogenic germline DNA
      repair gene mutations in men with prostate cancer, and identification of these
      features may help to select patients for germline testing. NCCN guidelines may be
      inadequate in predicting which prostate cancer patients should undergo genetic
      screening.

PMID- 29368342
TI  - Long-term effect of medical treatment of diarrhoea in 377 patients with SeHCAT
      scan diagnosed bile acid malabsorption from 2003 to 2016; a retrospective study.
AB  - BACKGROUND: Excessive amounts of bile acids entering the colon due to bile acid
      malabsorption cause chronic bile acid diarrhoea. Diagnosis is possible by
      measuring the retention fraction of orally ingested 75 Selenium homotaurocholic
      acid (SeHCAT). The knowledge of long-term effects of medical treatment is sparse.
      AIM: To describe diarrhoea, adherence to treatment, treatment effects and quality
      of life in a large, well-defined cohort of patients with bile acid diarrhoea.
      METHODS: A retrospective survey was performed among 594 patients with bile acid
      malabsorption verified by SeHCAT scans at our unit between 2003 and 2016.
      Questionnaires about medical history, diarrhoea, use of medication, and quality
      of life scores were mailed to all patients. RESULTS: Among 594 patients 377 (69%)
      responded. Among respondents, 121 (32%) had bile acid diarrhoea due to ileal
      disease or resection (type 1), 198 (52%) idiopathic bile acid diarrhoea (type 2)
      and 58 (16%) bile acid diarrhoea due to other non-ileal disease, mainly
      cholecystectomy (type 3). At follow-up, half of the patients, 184 (50%), reported
      improvement of diarrhoea. However, 273 patients (74%) still reported diarrhoea
      and 234 (62%) regularly used anti-diarrhoeal medication. In spite of treatment,
      235 (64%) considered reduced quality of life by diarrhoea and 184 (50%) reported
      that diarrhoea was unaltered or worse than before established diagnosis.
      CONCLUSION: Many patients with bile acid diarrhoea continue to have bothersome
      diarrhoea in spite of correct diagnosis and treatment.

PMID- 29368343
TI  - Ecological characterization of a tick community across a landscape gradient
      exhibiting differential anthropogenic disturbance in the Atlantic Forest
      ecoregion in Argentina.
AB  - An ecological analysis of a tick (Ixodida: Ixodidae) community across a landscape
      gradient presenting differential anthropogenic disturbance in the Atlantic Forest
      ecoregion in Argentina was performed. Ticks were collected from vegetation and
      hosts between September 2014 and August 2016. A total of 12 697 free-living ticks
      and 3347 specimens from hosts were collected, including 317 ticks infesting
      humans. The values obtained show considerable species diversity in the forest
      environment accompanied by low equitability. The similarity index derived from a
      comparison of forest and agricultural environments was higher than that
      calculated by comparing forest and urban environments. The data suggest that
      although a cycle of one generation per year is apparent in some species, more
      than one cohort may co-exist within the populations of some of these species.
      Well-marked patterns of the seasonal distribution of free-living tick species
      emerged in environments with no anthropic modification. The results indicate that
      forest environments are more suitable habitats than agricultural and urban
      environments for many species of native tick, but are unsuitable for exotic
      species that have successfully established in environments that have been
      modified by man.

PMID- 29368344
TI  - Association of toothbrushing and proximal cleaning with periodontal health among
      Korean adults: Results from Korea National Health and Nutrition Examination
      Survey in year 2010 and 2012.
AB  - AIM: Toothbrushing (TB), dental flossing (DF) and inter-dental brushing (IDB) are
      regarded as fundamental self-care methods for periodontal health. Few evidences
      on its effectiveness on periodontal health are available. Hence, this study aimed
      to evaluate the association of TB, DF, IDB and interaction effect with
      periodontal health. MATERIALS AND METHODS: The nationally representative 4,766
      Korean adults aged 19 years and older were cross-sectionally surveyed in 2010 and
      2012. Periodontal health was defined as Community Periodontal Index 1-2 for
      gingivitis and 3-4 for periodontitis. The information about variables was from
      interview and blood analyses. Multivariable logistic regression analyses and the
      interaction effect between TB and proximal cleaning (PC: DF and/or IDB) were
      applied. RESULTS: Toothbrushing thrice or more per day and DF were associated
      with a lower prevalence of periodontitis by both 44%, while the preventive
      fraction of DF on gingivitis was 30%. The preventive fraction of interaction
      effects between TB thrice or more and PC were 78% for periodontitis and 68% for
      gingivitis among 40-59 year age group. CONCLUSIONS: Toothbrushing and PC are
      independently associated with periodontal health. Hence, periodontists should
      recommend TB thrice or more per day and PC such as DF and IDB to promote
      periodontal health.

PMID- 29368345
TI  - Soil temperature effects on the structure and diversity of plant and invertebrate
      communities in a natural warming experiment.
AB  - Global warming is predicted to significantly alter species physiology, biotic
      interactions and thus ecosystem functioning, as a consequence of coexisting
      species exhibiting a wide range of thermal sensitivities. There is, however, a
      dearth of research examining warming impacts on natural communities. Here, we
      used a natural warming experiment in Iceland to investigate the changes in above
      ground terrestrial plant and invertebrate communities along a soil temperature
      gradient (10 degrees C-30 degrees C). The alpha-diversity of plants and
      invertebrates decreased with increasing soil temperature, driven by decreasing
      plant species richness and increasing dominance of certain invertebrate species
      in warmer habitats. There was also greater species turnover in both plant and
      invertebrate communities with increasing pairwise temperature difference between
      sites. There was no effect of temperature on percentage cover of vegetation at
      the community level, driven by contrasting effects at the population level. There
      was a reduction in the mean body mass and an increase in the total abundance of
      the invertebrate community, resulting in no overall change in community biomass.
      There were contrasting effects of temperature on the population abundance of
      various invertebrate species, which could be explained by differential thermal
      tolerances and metabolic requirements, or may have been mediated by changes in
      plant community composition. Our study provides an important baseline from which
      the effect of changing environmental conditions on terrestrial communities can be
      tracked. It also contributes to our understanding of why community-level studies
      of warming impacts are imperative if we are to disentangle the contrasting
      thermal responses of individual populations.

PMID- 29368346
TI  - Early risk pathways to physical versus relational peer aggression: The interplay
      of externalizing behavior and corporal punishment varies by child sex.
AB  - Children who aggress against their peers may use physical or relational forms,
      yet little research has looked at early childhood risk factors and
      characteristics that uniquely predict high levels of relational versus physical
      aggression in preadolescence. Accordingly, the main aim of our study was to link
      early corporal punishment and externalizing behavior to children's physical and
      relational peer aggression during preadolescence and to examine how these
      pathways differed by sex. Participants were 193, 3-year-old boys (39%) and girls
      who were reassessed following the transition to kindergarten (5.5 years) and
      preadolescence (10.5 years). A series of autoregressive, cross-lagged path
      analyses were conducted to examine the relationships between child externalizing
      problems and corporal punishment at ages 3 and 5.5 years, and their association
      with physical and relational aggression at age 10.5. Multiple group analysis was
      used to determine whether pathways differed by sex. Three developmental pathways
      were identified: (i) direct associations between stable childhood externalizing
      problems and later physical aggression; (ii) a direct pathway from early corporal
      punishment to preadolescent relational and physical peer aggression; and (iii) an
      indirect pathway from early corporal punishment to later physical aggression via
      continuing externalizing problems in middle childhood. Child sex moderated the
      nature of these pathways, as well as the direction of association between risk
      and outcome variables. These data advance our understanding of the etiology of
      distinct forms of peer aggression and highlight the potential for more
      efficacious prevention and intervention efforts in the early childhood years.

PMID- 29368347
TI  - RNA sequencing reveals distinct gene expression patterns during the development
      of parasitic larval stages of the salmon louse (Lepeophtheirus salmonis).
AB  - The salmon louse (Lepeophtheirus salmonis), an ectoparasitic copepod on
      salmonids, has become a major threat for the aquaculture industry. In search for
      new drugs and vaccines, transcriptome analysis is increasingly used to find
      differently regulated genes and pathways in response to treatment. However, the
      underlying gene expression changes going along with developmental processes could
      confound such analyses. The life cycle of L. salmonis consists of eight stages
      divided by moults. The developmental rate of salmon lice on the host is not
      uniform. Individual- and sex-related differences are found leading to individuals
      of unlike developmental status at same sampling time point after infection. In
      this study, we analyse L. salmonis from a time series by RNA sequencing applying
      a method of separating individuals of different instar age independent of
      sampling time point. Lice of four stages divided into up to four age groups
      within the stage were analysed in triplicate (total of 66 samples). Gene
      expression analysis shows that the method for sorting individuals was successful.
      Many genes show cyclic expression patterns over the moulting cycles. Overall gene
      expression differs more between lice of different age within the same stage than
      between lice of different stage but same instar age.

PMID- 29368349
TI  - Wrinkle and roughness measurement by the Antera 3D and its application for
      evaluation of cosmetic products.
AB  - BACKGROUND: Skin topographic measurements are of paramount importance in the
      field of dermo-cosmetic evaluation. The aim of this study was to investigate how
      the Antera 3D, a multi-purpose handheld camera, correlates with other topographic
      techniques and changes in skin topography following the use of a cosmetic
      product. METHODS: Skin topographic measurements were collected on 26 female
      volunteers aged 45-70 years with the Antera 3D, the DermaTOP and image analysis
      on parallel-polarized pictures. Different filters for analysis from the Antera 3D
      were investigated for repeatability, correlations with other imaging techniques
      and ability to detect improvements of skin topography following application of a
      serum. RESULTS: Most of Antera 3D parameters were found to be strongly correlated
      with the DermaTOP parameters. No association was found between the Antera 3D
      parameters and measurements on parallel-polarized photographs. The measurements
      repeatability was comparable among the different filters for analysis, with the
      exception of wrinkle max depth and roughness Rt. Following a single application
      of a tightening serum, both Antera 3D wrinkles and texture parameters were able
      to record significant improvements, with the best improvements observed with the
      large filter. CONCLUSION: The Antera 3D demonstrated its relevance for cosmetic
      product evaluation. We also provide recommendations for the analysis based on our
      findings.

PMID- 29368348
TI  - A calcium optimum for cytotoxic T lymphocyte and natural killer cell
      cytotoxicity.
AB  - KEY POINTS: Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are
      required to eliminate cancer cells. We analysed the Ca2+ dependence of CTL and NK
      cell cytotoxicity and found that in particular CTLs have a very low optimum of
      [Ca2+ ]i (between 122 and 334 nm) and [Ca2+ ]o (between 23 and 625 MUm) for
      efficient cancer cell elimination, well below blood plasma Ca2+ levels. As
      predicted from these results, partial down-regulation of the Ca2+ channel Orai1
      in CTLs paradoxically increases perforin-dependent cancer cell killing. Lytic
      granule release at the immune synapse between CTLs and cancer cells has a Ca2+
      optimum compatible with this low Ca2+ optimum for efficient cancer cell killing,
      whereas the Ca2+ optimum for CTL migration is slightly higher and proliferation
      increases monotonously with increasing [Ca2+ ]o . We propose that a partial
      inhibition of Ca2+ signals by specific Orai1 blockers at submaximal
      concentrations could contribute to tumour elimination. ABSTRACT: Cytotoxic T
      lymphocytes (CTLs) and natural killer (NK) cells are required to protect the
      human body against cancer. Ca2+ is a key metabolic factor for lymphocyte function
      and cancer homeostasis. We analysed the Ca2+ dependence of CTL and NK cell
      cytotoxicity against cancer cells and found that CTLs have a bell-shaped Ca2+
      dependence with an optimum for cancer cell elimination at rather low [Ca2+ ]o (23
      625 MUm) and [Ca2+ ]i (122-334 nm). This finding predicts that a partial
      inhibition of Orai1 should increase (rather than decrease) cytotoxicity of CTLs
      at [Ca2+ ]o higher than 625 MUm. We tested this hypothesis in CTLs and indeed
      found that partial down-regulation of Orai1 by siRNA increases the efficiency of
      cancer cell killing. We found two mechanisms that may account for the Ca2+
      optimum of cancer cell killing: (1) migration velocity and persistence have a
      moderate optimum between 500 and 1000 MUm [Ca2+ ]o in CTLs, and (2) lytic granule
      release at the immune synapse between CTLs and cancer cells is increased at 146
      MUm compared to 3 or 800 MUm, compatible with the Ca2+ optimum for cancer cell
      killing. It has been demonstrated in many cancer cell types that Orai1-dependent
      Ca2+ signals enhance proliferation. We propose that a decrease of [Ca2+ ]o or
      partial inhibition of Orai1 activity by selective blockers in the tumour
      microenvironment could efficiently reduce cancer growth by simultaneously
      increasing CTL and NK cell cytotoxicity and decreasing cancer cell proliferation.

PMID- 29368351
TI  - Visualization of viscoelastic behavior in skin equivalent using optical coherence
      tomography-based straingraphy.
AB  - BACKGROUND/PURPOSE: The relationships between the skin components and these
      mechanical roles are still unclear. To clarify these relationships, we
      investigated spatial mapping of the mechanical behavior of cultured skin
      equivalents (SEs) using optical coherence tomography (OCT)-based straingraphy.
      METHODS: We built a strain relaxation test system combined with OCT and developed
      an algorithm that could visualize a time-dependent strain distribution, named
      dynamic-optical coherence straingraphy (D-OCSA). Using this system, we analyzed
      how the spatial mechanical changes in the SEs depended on the culture duration.
      For quantitative analysis of viscoelastic behavior, we defined a relaxation
      attenuation coefficient of strain rate, which indicates the ratio of viscosity
      and elasticity in the Klevin-Voight model. RESULTS: By culturing for 4 days in
      comparison to culturing for 1 day, the strain relaxation attenuation coefficient
      of the whole skin, especially at the region of the dermal-epidermal junction
      (DEJ), significantly increased in the negative direction. In tissue slices taken
      for microscopy, several cracks were observed in the SEs cultured for 4 days.
      CONCLUSION: This study is the first to provide quantified evidence that the DEJ
      is a dynamically specialized region. An OCT-based straingraphy system (D-OCSA)
      would be beneficial for evaluating the quality of SEs, as well as functional
      analysis of their mechanics.

PMID- 29368350
TI  - Genotoxicity of fine and coarse fraction ambient particulate matter in
      immortalised normal (TT1) and cancer-derived (A549) alveolar epithelial cells.
AB  - Human exposure to airborne particulate matter (PM) is associated with adverse
      cardiopulmonary health effects, including lung cancer. Ambient PM represents a
      heterogeneous mixture of chemical classes including transition metals, polycyclic
      aromatic hydrocarbons (PAHs) and their derivatives such as nitro-PAHs, many of
      which are classified as putative carcinogens. As the primary site of human
      exposure to PM is the lungs, we investigated the response of two alveolar
      epithelial cell lines, the tumour-derived A549 and newly described TT1 cells, to
      fine and coarse PM collected from background and roadside locations. We show that
      coarse PM elicits a genotoxic response in the TT1 cells, with the strongest
      signal associated with the background sample. This response could be
      recapitulated using the organic extract derived from this sample. No responses
      were observed in PM-challenged A549 cells. Fine PM failed to elicit a genotoxic
      response in either cell line despite the higher PAH concentrations within this
      fraction. Consistent with the lack of a simplistic association between PM PAH
      content and the observed genotoxic response, TT1 cells treated with
      benzo[a]pyrene (BaP) demonstrated no increase in the selected markers. In
      contrast, a pattern of response was observed in TT1 cells challenged with 3
      nitrobenzanthrone (3-NBA) similar to that with coarse PM. Together, these data
      illustrated the suitability of the TT1 cell line for assessing PM-induced
      genotoxicity and challenge the contention that fine roadside PM poses the higher
      cancer risk. Furthermore, the response to 3-NBA and not BaP suggests a major
      contribution of nitro-PAHs to the overall toxicity of PM. Environ. Mol. Mutagen.
      59:290-301, 2018. (c) 2018 The Authors Environmental and Molecular Mutagenesis
      published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

PMID- 29368352
TI  - Robotic-assisted deep inferior epigastric artery perforator flap abdominal
      harvest for breast reconstruction: A case report.
AB  - The deep inferior epigastric perforator (DIEP) flap is a mainstay of autologous
      breast reconstruction. The da Vinci robot has recently been adapted for an
      increasing number of reconstructive surgeries. The literature has yet to describe
      its use for the intra-abdominal harvest of the deep inferior epigastric vessels
      (DIEV) during DIEP flap breast reconstruction. We show the use of the da Vinci
      robotic surgical system for the intra-abdominal dissection of DIEV during delayed
      breast reconstruction with a DIEP flap in a 51-year-old female who had undergone
      a right modified radical mastectomy. After dissecting the flap from the anterior
      abdominal wall leaving only the targeted perforating vessels intact, a 1.5 cm
      fascial incision was made adjacent to the perforator and the vessels were
      dissected to below the level of the fascia. The intra-abdominal robotic-assisted
      dissection of the DIEV up to the perforator was then completed. The DIEV were
      divided at their origin using the robot and the flap removed from the abdomen for
      subsequent reconstruction. This technique enabled improved precision of flap
      harvest while also decreasing the donor-site morbidity by minimizing the incision
      length of the anterior rectus sheath. The patient had an uneventful postoperative
      course and, at 9-month follow-up, exhibited no evidence of flap or donor-site
      complications, specifically hernia or bulge. This novel approach for the harvest
      of a DIEP flap introduces an alternative technique to the conventional DIEP flap
      procedure in the appropriate patient population. Risks inherent to this technique
      as well as additional costs must be considered.

PMID- 29368353
TI  - Effect of membrane exposure on guided bone regeneration: A systematic review and
      meta-analysis.
AB  - AIMS: This review aimed at investigating the effect of membrane exposure on
      guided bone regeneration (GBR) outcomes at peri-implant sites and edentulous
      ridges. MATERIAL AND METHODS: Electronic and manual literature searches were
      conducted by two independent reviewers using four databases, including MEDLINE,
      EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, for
      articles up to February 2017. Articles were included if they were human clinical
      trials or case series reporting outcomes of GBR procedures with and without
      membrane exposure. A random-effects meta-analysis was conducted, and the weighted
      mean difference (WMD) between the two groups and 95% confidence interval (CI)
      were reported. RESULTS: Overall, eight articles were included in the quantitative
      analysis. The WMD of the horizontal bone gain at edentulous ridges was -76.24%
      (95% CI = -137.52% to -14.97%, p = .01) between sites with membrane exposure and
      without exposure. In addition, the WMD of the dehiscence reduction at peri
      implant sites was -27.27% (95% CI of -45.87% to -8.68%, p = .004). Both analyses
      showed significantly favorable outcomes at the sites without membrane exposure.
      CONCLUSION: Based on the findings of this study, membrane exposure after GBR
      procedures has a significant detrimental influence on the outcome of bone
      augmentation. For the edentulous ridges, the sites without membrane exposure
      achieved 74% more horizontal bone gain than the sites with exposure. For peri
      implant dehiscence defects, the sites without membrane exposure had 27% more
      defect reduction than the sites with exposure.

PMID- 29368354
TI  - The evaluation of public health nursing students' skill achievement levels by
      educational improvement.
AB  - OBJECTIVE: This study aimed to evaluate the educational improvement outcomes
      after introducing undergraduate public health nursing electives from the
      perspective of students, teachers, and public health nurses. DESIGN AND SAMPLE:
      Post-test design with control group was used. We surveyed three groups of
      participants on the relevance of achieved skill items. These groups were as
      follows: fourth-year students, teaching staff from seven universities, and public
      health nurses from special districts of Tokyo who had pioneered the introduction
      of public health nursing electives. MEASURES: The three participant groups were
      surveyed in 2013 and 2014 to compare the students' levels of achievement in the
      98 skill items presented by the Japanese Ministry of Health, Labour, and Welfare.
      Practical training introduced educational reform in 2014. Anonymous self
      administrated questionnaires were used. RESULTS: The mean achievement rates of
      the 98 items in 2013 and 2014 were 67.9% and 72.6%, respectively, for students;
      40.9% and 59.7% for teachers; and 44.4% and 59.4% for PHNs. A significant
      difference was observed between ratios of 2013 and 2014 in all three groups.
      CONCLUSIONS: The results demonstrated that the introduction of educational reform
      increased the achievement rates of students through the electives.

PMID- 29368355
TI  - Artificial intelligence in diabetes care.

PMID- 29368356
TI  - Superior anticancer activity is demonstrated by total extract of Curcuma longa L.
      as opposed to individual curcuminoids separated by centrifugal partition
      chromatography.
AB  - Three curcuminoids: bisdemethoxycurcumin, demethoxycurcumin, and curcumin from
      turmeric were successfully separated by a high capacity solvent system composed
      of heptane: chloroform: methanol: water mixture (5: 6: 3: 2 v/v/v/v) tailored for
      centrifugal partition chromatographs at K-values of 0.504, 1.057, 1.644,
      respectively. These three ferulic acid derivatives obtained at a purity rate
      exceeding 95% were analysed by an HPLC-MS spectrometer. Turmeric extract
      inhibited the proliferation/viability of A549 human lung cancer, HT29 colon
      cancer, and T98G glioblastoma cell lines in (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide) tetrazolium reduction assay (MTT). Single
      curcuminoids significantly decreased the viability/proliferation of lung cancer
      cells in a dose-dependent manner. However, total extract displayed the superior
      anticancer activity in the investigated cell lines. Crude extract in combination
      with cisplatin augmented the decrease in the viability of cancer cells compared
      with single compound treatment in A549 lung cancer cells. Total extract of
      Curcuma longa could be regarded as being more effective against lung cancer cells
      in vitro than its separated compounds.

PMID- 29368357
TI  - Puerarin inhibits TRPM3/miR-204 to promote MC3T3-E1 cells proliferation,
      differentiation and mineralization.
AB  - Puerarin is an isoflavonoid phytoestrogen extracted from the root of Radix
      Pueraria, has attracted increasing attention because of its beneficial effects on
      anti-osteoporosis, but the molecular mechanisms underlying its actions on
      osteoblasts are not fully understood. The current study aimed to investigate the
      effect of puerarin on MC3T3-E1 osteoblastic cells proliferation, differentiation
      and mineralization, in vitro and its underlying mechanisms. The results indicated
      that puerarin significantly promoted the osteoblasts proliferation, enhanced
      alkaline phosphatase activity and increased the formation of mineralized nodules.
      Following treatment with puerarin, the expression levels of transient receptor
      potential Melastatin 3 (TRPM3) and microRNA-204 (miR-204) were decreased, whereas
      that of Runt-related transcription Factor 2 (Runx2) increased. TRPM3-small
      interfering RNA and 2-aminoethoxydiphenyl borate (2-APB, inhibitor of TRPM3)
      promoted the expression of Runx2 and thus improved the development of
      osteoblasts, but pregnenolone sulfate, which is the agonist of TRPM3, inhibited
      the effects. In addition, puerarin induced the changes of intracellular Ca2+
      concentration ([Ca2+ ]i ) and extracellular Ca2+ concentration ([Ca2+ ]0 )
      through TRPM3 might be involved in the biological process of MC3T3-E1 cells.
      These results suggested that puerarin may promote MC3T3-E1 cell proliferation,
      differentiation and mineralization, which may be related to the downregulation of
      TRPM3/miR-204 and following regulating [Ca2+ ]i and [Ca2+ ]0 , and activation of
      Runx2.

PMID- 29368358
TI  - Birth order and paediatric allergic disease: A nationwide longitudinal survey.
AB  - BACKGROUND: Environmental factors seem to be related to the incidence of allergic
      disease. Children with a later birth order are often exposed to environments,
      where pathogens and endotoxins can be found, and thus have a higher risk of
      developing infectious diseases. Therefore, birth order is regarded as an
      indicator that reflects post-natal environment. However, longitudinal studies are
      limited on this subject. This study sought to elucidate the relationships between
      birth order and allergic disease. METHODS: From a nationwide longitudinal study
      that followed children born in 2001 (n = 47 015), we selected doctors' visits for
      3 types of allergic disease-bronchial asthma, food allergy and atopic dermatitis
      from infancy to 12 years of age and conducted binomial log-linear regression
      analysis to evaluate the associations between birth order and these diseases. We
      adjusted for the child and parental factors and estimated risk ratio (RR) and 95%
      confidence interval (CI) for each outcome. RESULTS: The associations between
      birth order and bronchial asthma were diverse; later birth order increased the
      risk in early childhood, but decreased the risks during school age. For example,
      the adjusted RR comparing third-born or higher and first-born children was 1.19
      (95% CI, 1.05-1.35) between 30 and 42 months of age, but was 0.76 (95% CI, 0.65
      0.89) between 10 and 11 years. Later birth order was generally protective for
      food allergy but increased the risk of atopic dermatitis. CONCLUSION: The
      influence of birth order depended on the type of allergic disease and the
      childhood period. Childhood is unique in terms of physical and immunological
      development, and the immune response to the post-natal environment in childhood
      appears to be heterogeneous.

PMID- 29368359
TI  - Norwegian standard for the safe practice of anaesthesia.

PMID- 29368360
TI  - International medical graduates and unfilled positions in abdominal transplant
      surgery fellowships in the United States.

PMID- 29368361
TI  - Impact of cold ischemia time on the outcomes of kidneys with Kidney Donor Profile
      Index >=85%: mate kidney analysis - a retrospective study.
AB  - The new kidney allocation system recommends local and regional sharing of
      deceased donor kidneys (DDK) with 86-100% Kidney Donor Profile Index (KDPI) to
      minimize discard. Regional sharing can increase cold ischemia time (CIT) which
      may negatively impact transplant outcomes. Using a same donor mate kidney model,
      we aimed to define a CIT that should be targeted to optimize outcomes. Using
      Organ Procurement and Transplant Network/United Network for Organ Sharing
      database, we identified recipients of DDK from 2000 to 2013 with >=85% KDPI. From
      this cohort, three groups of mate kidney recipients were identified based on CIT:
      group 1 (>=24 vs. >=12 to <24 h), group 2 (>=24 vs. <12 h), and group 3 (>=12 to
      <24 vs. <12 h). Adjusted delayed graft function (DGF), and graft and patient
      survivals were compared for mate kidneys. DGF risk was significantly lower for
      patients with CIT <12 vs. >=24 h in group 2 (adjusted OR: 0.25, 95% CI: 0.12
      0.57, P < 0.001) while trending lower for CIT >=12 to <24 vs. >=24 h in group 1
      (adjusted OR: 0.78, 95% CI: 0.59-1.03, P = 0.08) and CIT <12 vs. >=12 to <24 h in
      group 3 (adjusted OR: 0.74, 95% CI: 0.55-1.0, P = 0.05). Adjusted graft and
      patient survivals were similar between mate kidneys in all groups. Minimizing CIT
      improves outcomes with regional sharing of marginal kidneys.

PMID- 29368362
TI  - Non-alcoholic fatty liver disease: an emerging predictor of stroke risk, severity
      and outcome.

PMID- 29368364
TI  - Seed-dispersal interactions in fragmented landscapes - a metanetwork approach.
AB  - Mutualistic interactions repeatedly preserved across fragmented landscapes can
      scale-up to form a spatial metanetwork describing the distribution of
      interactions across patches. We explored the structure of a bird seed-dispersal
      (BSD) metanetwork in 16 Neotropical forest fragments to test whether a distinct
      subset of BSD-interactions may mediate landscape functional connectivity. The
      metanetwork is interaction-rich, modular and poorly connected, showing high beta
      diversity and turnover of species and interactions. Interactions involving large
      sized species were lost in fragments < 10 000 ha, indicating a strong filtering
      by habitat fragmentation on the functional diversity of BSD-interactions.
      Persistent interactions were performed by small-seeded, fast growing plant
      species and by generalist, small-bodied bird species able to cross the fragmented
      landscape. This reduced subset of interactions forms the metanetwork components
      persisting to defaunation and fragmentation, and may generate long-term deficits
      of carbon storage while delaying forest regeneration at the landscape level.

PMID- 29368363
TI  - Cost-effectiveness of possible future smoking cessation strategies in Hungary:
      results from the EQUIPTMOD.
AB  - AIMS: To evaluate potential health and economic returns from implementing smoking
      cessation interventions in Hungary. METHODS: The EQUIPTMOD, a Markov-based
      economic model, was used to assess the cost-effectiveness of three implementation
      scenarios: (a) introducing a social marketing campaign; (b) doubling the reach of
      existing group-based behavioural support therapies and proactive telephone
      support; and (c) a combination of the two scenarios. All three scenarios were
      compared with current practice. The scenarios were chosen as feasible options
      available for Hungary based on the outcome of interviews with local stakeholders.
      Life-time costs and quality-adjusted life years (QALYs) were calculated from a
      health-care perspective. The analyses used various return on investment (ROI)
      estimates, including incremental cost-effectiveness ratios (ICERs), to compare
      the scenarios. Probabilistic sensitivity analyses assessed the extent to which
      the estimated mean ICERs were sensitive to the model input values. RESULTS:
      Introducing a social marketing campaign resulted in an increase of 0.3014
      additional quitters per 1 000 smokers, translating to health-care cost-savings of
      ?0.6495 per smoker compared with current practice. When the value of QALY gains
      was considered, cost-savings increased to ?14.1598 per smoker. Doubling the reach
      of existing group-based behavioural support therapies and proactive telephone
      support resulted in health-care savings of ?0.2539 per smoker (?3.9620 with the
      value of QALY gains), compared with current practice. The respective figures for
      the combined scenario were ?0.8960 and ?18.0062. Results were sensitive to model
      input values. CONCLUSIONS: According to the EQUIPTMOD modelling tool, it would be
      cost-effective for the Hungarian authorities introduce a social marketing
      campaign and double the reach of existing group-based behavioural support
      therapies and proactive telephone support. Such policies would more than pay for
      themselves in the long term.

PMID- 29368365
TI  - Phlorotannin supplement decreases wake after sleep onset in adults with self
      reported sleep disturbance: A randomized, controlled, double-blind clinical and
      polysomnographic study.
AB  - Our previous study demonstrated that phlorotannin supplement had a sleep
      promoting effect in rodents. In the present study, we investigated whether the
      phlorotannin supplement could improve sleep in subjects with self-reported sleep
      disturbances. In a randomized, double-blind, placebo-controlled trial, 24
      subjects consumed either a placebo or phlorotannin supplement (500 mg/day) for 1
      week, 30-60 min prior to bedtime. Sleep parameters were assessed at baseline and
      at 1 week with sleep questionnaires and polysomnography. At the end of the
      treatment period, the complete sets of sleep parameters from 20 subjects.
      Phlorotannin resulted in a significant increase in "Sleep duration" scores
      compared to the placebo (p = .044), although there were no significant
      differences on the total PSQI scores. Polysomnography revealed that wakefulness
      after sleep onset was significantly lower in the phlorotannin group compared to
      the placebo group (phlorotannin vs. placebo, -25.5 +/- 30.5 vs. -1.7 +/- 14.9; p
      = .045) as well as total wake time (phlorotannin vs. placebo, -0.9 +/- 3.0 vs. 
      6.1 +/- 6.8; p = .048). Additionally, the respiratory disturbance index during
      supine rapid eye movement sleep was significantly lower in the phlorotannin group
      (p = .035). There were no serious adverse effects in either group. Our data
      suggest that the phlorotannin supplement improved sleep maintenance (WHO ICTRP:
      KCT0001892).

PMID- 29368366
TI  - In ineffective esophageal motility, failed swallows are more functionally
      relevant than weak swallows.
AB  - BACKGROUND: Esophageal pressure topography (EPT) diagnosis of ineffective
      esophageal motility (IEM) can be non-specific with unclear clinical significance.
      AIMS: To determine whether peristaltic vigor or lower esophageal sphincter (LES)
      integrity is associated with poor clearance and acid reflux in IEM. METHODS:
      Bolus clearance on high-resolution impedance manometry (HRIM) and available
      reflux studies in patients with IEM were retrospectively reviewed. Bolus
      clearance was assessed using both line tracing and colored contour methods on
      HRIM. EPT parameters, bolus clearance, and acid reflux variables were explored.
      KEY RESULTS: Eighty-eight patients with IEM were included. Bolus clearance
      occurred in 71% of all swallows, and 55.7% of patients had complete bolus transit
      (CBT, bolus clearance in >=80% of swallows). Bolus clearance was impaired in
      swallows with distal contractile integral (DCI) <100 mmHg*cm*s compared to DCI
      100-450 (0.43 vs 0.79, P < .0001). A cutoff at DCI 100 mmHg*cm*s was associated
      with clearance with an accuracy of 76% compared to 49% at DCI 450 (P = .0001 for
      both). A median DCI <100 was associated with a higher Eckardt score (9 vs 3, P =
      .03), and on reflux testing available in 47 patients, with abnormal acid exposure
      time (P = .002). Peristaltic reserve (PR) defined as (DCI of multiple rapid
      swallow/median DCI of wet swallows), integrated relaxation pressure, and resting
      lower esophageal sphincter pressure were not associated with clearance or acid
      exposure. CONCLUSIONS & INFERENCES: Failed peristalsis, as defined by DCI <100
      mmHg*cm*s, is associated with impaired bolus clearance and more severe dysphagia
      in IEM, and likely abnormal acid exposure.

PMID- 29368367
TI  - The effects of dietary calcium iodate on productive performance, egg quality and
      iodine accumulation in eggs of laying hens.
AB  - The aim of this study was to examine the effects of various levels of
      supplemental calcium iodate (CI) on productive performance, egg quality, blood
      indices and iodine (I) accumulation in the eggs in commercial laying hens. A
      total of 240 White Leghorn layers (Hy-line W36) were divided through a completely
      randomized design into six treatments with five replicates and eight hens per
      each at 32 weeks of age. This experiment lasted for 12 weeks. Concentrations of I
      in the mash diets were 0.74, 3.13, 5.57, 8.11, 10.65 and 12.94 mg I/kg of feed in
      treatments 1-6 respectively. The added doses of CI were included 0.0 (control),
      2.5, 5.0, 7.5, 10.0 and 12.5 mg/kg of diet for treatments 1-6 respectively. There
      were no significant differences in productive performance among the treatments.
      The highest eggshell strength was observed in group fed diet containing 3.13 mg
      I/kg (p = .014). The highest percentage of calcium and lowest percentage of
      phosphorus in eggshell were observed in group fed diet containing 12.94 mg I/kg
      (p = .0001). Feeding hens with diet containing 12.94 mg I/kg increased serum
      triiodothyronine-to-thyroxine ratio (p = .0001). Serum alanine aminotransferase
      activity in hens fed diet containing 12.94 mg I/kg was significantly more than
      control (p = .041). Blood Serum triglycerides in hens fed diet containing 8.11 mg
      I/kg were significantly higher than control (p = .0001). Edible fraction of the
      eggs of birds fed diet containing 12.94 mg I/kg was enriched by I almost 3 times
      more than those fed diet containing 0.74 mg I/kg. The results suggested that egg
      production, egg mass, feed intake and feed conversion ratio were not
      significantly affected by dietary I levels. Iodine accumulation in the eggs were
      increased by increasing dietary I levels and the level of 10 mg/kg CI could
      supply I enrichment of the eggs.

PMID- 29368368
TI  - FOXK2 suppresses the malignant phenotype and induces apoptosis through inhibition
      of EGFR in clear-cell renal cell carcinoma.
AB  - Forkhead box K2 (FOXK2) belongs to the forkhead box transcription factor family.
      Recent studies have revealed that FOXK2 plays essential roles in cancer cell
      proliferation and survival. However, the biological function of FOXK2 in renal
      cell carcinoma remains unexplored. In our study, we demonstrated that FOXK2 mRNA
      and protein levels were decreased in clear-cell renal cell carcinoma (ccRCC)
      tissues compared to those in corresponding non-tumor renal tissues, and decreased
      FOXK2 levels were associated with poor prognosis in ccRCC patients after
      nephrectomy. FOXK2 suppressed proliferation, migration and invasion capabilities
      of ccRCC cells and induced cellular apoptosis in vitro. Moreover, we found that
      FOXK2 overexpression inhibited xenograft tumor growth and promoted apoptosis in
      vivo. Genome-wide transcriptome profiling using FOXK2 overexpressed 769-P cells
      revealed that the epidermal growth factor receptor (EGFR) was a potential
      downstream gene of FOXK2. Overexpression of EGFR is able to rescue the inhibited
      proliferation capacity and the enhanced apoptosis capacity due to the
      overexpression of FOXK2 in 769-P cells. Collectively, our results indicate that
      FOXK2 inhibits the malignant phenotype of ccRCC and acts as a tumor suppressor
      possibly through the inhibition of EGFR.

PMID- 29368369
TI  - Recent developments and controversies in transcatheter aortic valve implantation.
AB  - Interventional cardiology has been revolutionised by transcatheter aortic valve
      implantation (TAVI), which has become established as the benchmark treatment for
      severe aortic stenosis in patients at high risk for surgical aortic valve
      replacement (AVR). Increased procedural familiarity and progression in device
      technology has enabled improvements to be made in complication rates, which have
      led to a commensurate expansion in the use of TAVI; it is now a viable
      alternative to AVR in patients at intermediate surgical risk, and has been used
      in cohorts such as those with bicuspid aortic valves or pure, severe aortic
      regurgitation. Given the rapid expansion in the use of TAVI, including cohorts of
      younger patients with fewer co-morbidities, attention must be paid to further
      reducing remaining complications, such as cardiac tamponade or stroke. To this
      end, novel techniques and devices have been devised and trialled, with varying
      levels of success. Furthermore, significant work has gone into refining the
      technique with exploration of alternative imaging modalities, as well as
      alternative access routes to provide greater options for patients with
      challenging vascular anatomy. Whilst significant progress has been made with
      TAVI, areas of uncertainty remain such as the management of concomitant coronary
      artery disease and the optimum post-procedure antiplatelet regimen. As such,
      research in this field continues apace, and is likely to continue as use of TAVI
      becomes more widespread. This review provides a summary of the existing evidence,
      as well as an overview of recent developments and contentious issues in the field
      of TAVI.

PMID- 29368370
TI  - Epoxides as Alkylating Reagents for the Catellani Reaction.
AB  - We report a cooperative catalytic system comprising a PdII complex, XPhos, and
      the potassium salt of 5-norbornene-2-carboxylic acid that enables the use of
      epoxides as alkylating reagents in the Catellani reaction, thereby expanding the
      existing paradigm of this powerful transformation. The potassium salt of
      inexpensive 5-norbornene-2-carboxylic acid acts as both mediator and base in the
      process. This mild, chemoselective, scalable, and atom-economical protocol is
      compatible with a wide variety of readily available functionalized aryl iodides
      and epoxides, as well as terminating olefins. The resulting products undergo
      facile oxa-Michael addition to furnish ubiquitous isochroman scaffolds.

PMID- 29368371
TI  - The association of nursing care perception with coping skills and posttraumatic
      growth in mental disorders.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Although it is well known that coping with
      mental disorder is a traumatic experience, studies of the relationships between
      posttraumatic growth and the variables that can affect it are rarely found in the
      literature. The studies that do exist usually focus on posttraumatic growth after
      posttraumatic stress disorder has developed as a result of traumatic life events
      such as earthquakes, wars, accidents or physical disease. In the literature,
      there exist few studies of patients diagnosed with psychosis. WHAT DOES THIS
      PAPER ADD TO EXISTING KNOWLEDGE?: This study shows that posttraumatic growth can
      be seen in patients after the diagnosis of mental disorders. Patients who use
      effective coping methods show more posttraumatic growth. In addition, patients
      who are satisfied with the nursing care received in the clinic show more
      posttraumatic growth. This indicates that care delivered by psychiatric nurses
      contributes to the posttraumatic growth of the patients. WHAT ARE THE
      IMPLICATIONS FOR PRACTICE?: Psychiatric nurses who recognize that suffering a
      mental disorder is a traumatic experience and that patients can grow from this
      experience can contribute to the posttraumatic growth of those in their care.
      When they see signs of posttraumatic growth, nurses can teach patients how to
      cope with that stress effectively and how to share their feelings, thoughts and
      experiences related to the situation. In addition, psychosocial interventions
      such as trauma-focused cognitive behavioural therapy and eye movement
      desensitization can be used to aid posttraumatic growth. ABSTRACT: Introduction
      Although it is recognized that suffering a mental illness is a traumatic
      experience, the fact that this can lead to posttraumatic growth and the variables
      that may affect the situation are rarely discussed in the literature. Aim This
      study was conducted to determine the effects of coping styles and nursing care
      perceptions on posttraumatic growth in mental disorders. Method The descriptive
      study was conducted at a psychiatric clinic with a personal information form and
      three-scale test. Results In the study, completed with 122 psychiatric
      inpatients, it was found that patients were using effective methods to cope with
      stress, were satisfied with nursing care and had high posttraumatic growth.
      Moreover, it was found that effective coping styles and satisfaction with nursing
      care positively affected the posttraumatic growth level of patients. Discussion
      The results support the proposition that using effective coping styles and
      seeking professional support after traumatic life events influence posttraumatic
      growth levels. Implications for practice Psychiatric nurses should be aware of
      the fact that developing a mental disorder is a traumatic life event after which
      posttraumatic growth can occur. They should encourage posttraumatic growth by
      teaching effective coping methods, providing psychiatric care and using
      psychosocial interventions such as trauma-focused cognitive behavioural therapy
      and eye movement desensitization.

PMID- 29368372
TI  - Age-related changes in fiber tracts in healthy adult brains: A generalized q
      sampling and connectometry study.
AB  - BACKGROUND: Generalized q-sampling (GQI) and connectometry analysis provide new
      indices, i.e., quantitative anisotropy (QA) and spin distribution function (SDF)
      in comparison with diffusion tensor imaging (DTI). They may provide more age
      related changes in white matter (WM) in aging. PURPOSE: To investigate the
      feasibility of using GQI and connectometry analysis to determine WM properties
      changes in aging. STUDY TYPE: Cross-cohort research. POPULATION: Fifty normal
      adults (27 females) aged 21-71 years. FIELD STRENGTH/SEQUENCE: T1 -weighted
      images (T1 WI) and high angular resolution diffusion imaging (HARDI) images were
      acquired at 1.5T. ASSESSMENT: HARDI data were analyzed using DTI and GQI to
      obtain fractional anisotropy (FA), QA, fiber numbers, and fiber lengths for tract
      analysis and using q-space diffeomorphic reconstruction (QSDR) for the
      connectometry analysis. We compared differences of DTI, GQI, and connectometry
      analysis to reflect WM changes in aging. STATISTICAL TESTS: Associations between
      FA, QA, and fiber numbers and lengths and age were analyzed using Pearson's
      correlation coefficients. The connectometry analysis was conducted using a
      multiple linear regression analysis, including age and gender as factors.
      Uncorrected P-value/false discovery rate (FDR) (corrected for multiple
      comparisons) < 0.05 was considered statistically significant. RESULTS: More
      regional changes were detected in FA related to age than changes in QA (17 > 6
      regions, P < 0.05). Fewer regional changes in fiber numbers and more changes of
      fiber lengths were observed for DTI than for GQI (5 < 8/10 > 7 regions, P <
      0.05). However, DTI and GQI analyses revealed consistent results in some regions,
      including the genu of the corpus callosum (GCC), body of the corpus callosum
      (BCC), fornix (Fx), and anterior coronal radiation (ACR) (P < 0.05). The
      connectometry analysis showed more tract changes associated with age at an FDR of
      0.05, which partially overlapped with the FA and QA. DATA CONCLUSION: GQI and
      connectometry provide more information about age-related tracts and complement
      the DTI findings. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN.
      RESON. IMAGING 2018;48:369-381.

PMID- 29368374
TI  - The promise of patient-reported outcomes: one step closer to routine care.

PMID- 29368373
TI  - Purple corn-associated rhizobacteria with potential for plant growth promotion.
AB  - AIMS: Purple corn (Zea mays var. purple amylaceum) is a native variety of the
      Peruvian Andes, cultivated at 3000 m since the pre-Inca times without N
      fertilization. We aimed to isolate and identify native plant growth-promoting
      rhizobacteria (PGPR) for future microbial-based inoculants. METHODS AND RESULTS:
      Eighteen strains were isolated from the rhizosphere of purple corn plants grown
      without N fertilization in Ayacucho (Peru). The 16S rRNA gene clustered the 18
      strains into nine groups that contained species of Bacillus, Stenotrophomonas,
      Achromobacter, Paenibacillus, Pseudomonas and Lysinibacillus. A representative
      strain from each group was selected and assayed for N2 fixation, phosphate
      solubilization, indole acetic and siderophore production, 1-aminocyclopropane-1
      carboxylic acid deaminase activity and biocontrol abilities. Inoculation of
      purple corn plants with single and combined strains selected after a principal
      component analysis caused significant increases in root and shoot dry weight,
      total C and N contents of the plants. CONCLUSIONS: PGPRs can support growth and
      crop production of purple corn in the Peruvian Andes and constitute the base for
      microbial-based inoculants. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      enlarges our knowledge on plant-microbial interactions in high altitude mountains
      and provides new applications for PGPR inoculation in purple amylaceum corn,
      which is part of the staple diet for the native Quechua communities.

PMID- 29368375
TI  - Fracture resistance of prepared premolars restored with bonded new lab composite
      and all-ceramic inlay/onlay restorations: Laboratory study.
AB  - OBJECTIVES: To assess the influence of new light curing lab composite, lithium
      disilicate glass-ceramic and yttrium-stabilized zirconia-based ceramic on the
      fracture resistance of maxillary premolars with class II inlay and onlay
      preparations. METHODS: Seventy sound maxillary premolars were divided randomly
      into seven main groups. The first group was left intact (control group). The
      remaining six groups were prepared with inlay and onlay cavities and restored
      with lab composite (SR Nexco), lithium-disilicate glass-ceramic (IPS e.max Press)
      and yttrium-stabilized zirconia-based ceramic (ICE Zirkon). The restorations were
      cemented with luting resin composite (Variolink N). All specimens were
      thermocycled 5000 cycles between 5 degrees C +/- 2 degrees C and 55 degrees C +/-
      2 degrees C and were then cyclic loaded for 500 000 cycles. The specimens were
      subjected to a compressive load in a universal testing machine using a metal
      sphere until fracture occurred. The results were analyzed by 2-way ANOVA and
      Tukey HSD post hoc tests. The level of significance was set at P < .05. RESULTS:
      There were no statistically significant differences among the means of control
      group and the groups restored with zirconia ceramic inlays and onlays (P > .05).
      However, statistically significant differences were found among the means of
      control group and the groups restored with lab composite inlays, lab composite
      onlays, pressable glass ceramic inlays and pressable glass ceramic onlays (P <
      .05). CONCLUSIONS: The fracture resistance of prepared teeth for inlay and onlay
      restorations is inferior to the intact teeth when lab composite is used.
      Conversely, when a ceramic material being used, the prepared teeth for inlay and
      onlay restorations showed a comparable strength to the intact teeth especially
      zirconia ceramic. CLINICAL SIGNIFICANCE: Premolar teeth restored with zirconia
      ceramic inlays and onlays exhibited fracture resistance comparable to intact
      teeth.

PMID- 29368376
TI  - Using cadaveric simulation to introduce the concept and skills required to start
      performing transanal total mesorectal excision.
AB  - AIM: The aim was to document the outcomes of surgeons attending a cadaveric
      simulation course designed to provide an introduction to transanal total
      mesorectal excision (TaTME). METHOD: This was a prospective observational study
      documenting the outcomes from classroom and wet lab activities. Follow-up
      questionnaires were used to monitor clinical activity after the course. RESULTS:
      Outcomes of 65 delegates from 12 different countries attending seven cadaveric
      simulation courses are described. Median time to insert and close the rectal
      purse-string was 15 min (range 7-50 min) and median time to complete the
      transanal mesorectal dissection was 105 min (range 60-260 min). Objective
      assessment of specimen quality showed that 42% of specimens were complete, 47%
      nearly complete and 11% were incomplete. Failure of the intraluminal rectal purse
      string was the most common difficulty encountered. Within 6 months of attending
      the course, nearly half (26/55; 47%) of the surgeons who responded had performed
      between 1 and 13 TaTMEs. Only 8/26 (31%) of the surgeons had arranged mentoring
      for their first case. CONCLUSION: This training model provides high levels of
      trainee satisfaction and the knowledge and technical skills to enable them to
      start performing TaTME. There is still work to do to provide adequate supervision
      and mentorship for surgeons early on their learning curve that is essential for
      the safe introduction of this new technique.

PMID- 29368377
TI  - Omalizumab updosing allows disease activity control in patients with refractory
      chronic spontaneous urticaria.

PMID- 29368379
TI  - Pancytopenia and megaloblastic erythropoiesis reveal a novel GIF mutation.

PMID- 29368378
TI  - Placental basement membrane proteins are required for effective cytotrophoblast
      invasion in a three-dimensional bioprinted placenta model.
AB  - Fetal cytotrophoblast invasion of maternal decidual vasculature is necessary to
      normal pregnancy. In preeclampsia, there is shallow invasion and abnormal
      remodeling of the uterine vasculature that lead to significant maternal and
      perinatal morbidity and mortality. The placental basement membrane (BM) proteins
      (e.g., laminin and collagen) has been implicated in the development of placenta
      while the level of laminin is significantly lower in preeclampsia. However, there
      are very limited studies, if any, on the effect of extracellular matrix (ECM)
      microenvironment on the invasion of cytotrophoblast. In this study, we
      hypothesized that placental BM proteins are required for effective
      cytotrophoblast invasion. Using proteomics, we found that more than 80% of ECM
      proteins in placental basal plate (pECM) were BM proteins. In addition to
      upregulating expressions of MMP2 (1.5-fold) and MMP9 (6.3-fold), pECM
      significantly increased the motility rates of cytotrophoblasts by 13-fold (from
      5.60 +/- 0.95 to 75.5 +/- 21.8 um/day) to achieve an effective invasion rate that
      was comparable to in vivo results. Treatments with PI3K inhibitors completely
      removed the pECM-enhanced invasive phenotypes and genotypes of cytotrophoblasts,
      suggesting its dominant role in cytotrophoblast-ECM interactions. Our results
      described, for the first time, the substantial effects of the ECM
      microenvironment on regulating cytotrophoblast invasion, an area that is less
      investigated but appear to be critical in the pathogenesis of preeclampsia.
      Moreover, the approach presented in this work that fabricates organ models with
      organ-specific ECM can be an attractive option to screen and develop novel
      therapeutics and biomarkers not only in preeclampsia but also other diseases such
      as cancer metastasis. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A:
      106A: 1476-1487, 2018.

PMID- 29368381
TI  - Development and internal validation of the Simplified Mortality Score for the
      Intensive Care Unit (SMS-ICU).

PMID- 29368380
TI  - Risk of rhabdomyolysis from 5-alpha reductase inhibitors.
AB  - PURPOSE: A recent regulatory warning and case reports have described the
      development of muscle complications with the use of 5-alpha reductase inhibitors
      (5ARIs). We wished to determine if there was a link between rhabdomyolysis and
      5ARI usage. METHODS: We used a matched cohort design and linked administrative
      data from the province of Ontario, Canada, to investigate the risk of
      rhabdomyolysis in men using either finasteride or dutasteride. A total of 99
      covariates were measured. We identified 93 197 men >=66 years of age who
      initiated a new prescription for a 5ARI, and they were matched using a propensity
      score to an equal number of men not prescribed a 5ARI. RESULTS: New initiation of
      5ARIs was not associated with a significantly increased risk of rhabdomyolysis
      (hazard ratio [HR] 1.21, 95% confidence interval [CI], 1.00-1.48, P = .06). When
      we examined the risk of rhabdomyolysis in the year prior to the initiation of a
      5ARI, we found that men who would go on to use a 5ARI in the future had an
      elevated risk of rhabdomyolysis even prior to starting the medication (HR 1.31,
      95% CI, 1.05-1.64, P = .01). Our secondary outcome of myositis and myopathy was
      significantly higher among 5ARI users (HR 1.63, 95% CI, 1.48-1.80, P < .01), and
      this risk was not present prior to 5ARI usage. CONCLUSION: 5-alpha reductase
      inhibitors do not appear to be associated with the development of rhabdomyolysis;
      however, they may be associated with an increased risk of myopathy and myositis.

PMID- 29368382
TI  - Translucency and masking properties of two ceramic materials for heat-press
      technology.
AB  - OBJECTIVES: To assess the translucency of two pressable ceramics and to analyze
      their masking property when placed on different tooth-shaded backgrounds.
      MATERIALS AND METHODS: Thirty discs (1-mm thickness) were fabricated using two
      pressable ceramics (shade/translucency): 1M1T/HT, 1M2T/HT, 2M2T (VITA PM9), and
      A1LT/HT, B1LT/HT, A2LT (e.max Press). Color measurements of discs were performed
      with a dental spectrophotometer on tooth-colored backgrounds (A1/A2/A3/A3.5/A4),
      and black and white backings. The masking property was calculated as the color
      difference (CIEDE2000) between parameters of discs on control (A1, A2) and test
      backgrounds (A3, A3.5, A4). One-way ANOVA was used for assessing differences in
      translucency parameter (TP) between ceramics. Two-way ANOVA was used for
      detecting differences among groups when measured over tooth-shaded backgrounds
      (alpha = 0.05, Bonferroni correction). RESULTS: TP ranged between 14.96 (B1LT)
      and 25.18 (1M1HT). A significant difference in TP was found between tested
      ceramics (F = 949.949, P < .001). However, TP did not vary significantly between
      1M1HT and 1M2HT (P > .05), 1M1T, A1HT and B1HT (P > .05), 1M2T, 2M2T, and A2HT (P
      > .05). A significant interaction effect of underlying background on color of
      ceramic discs was found (F = 107.994, P < .001). CONCLUSION: VITA PM9
      demonstrated higher translucency than e.max Press ceramics. Except A1LT, all
      ceramic materials evaluated showed poor masking properties on A4 background.
      CLINICAL SIGNIFICANCE: Highly translucent ceramics should be wisely used for
      restoring the appearance of dental structures since background color has a large
      effect upon these materials. The more recently introduced pressable ceramics
      showed high levels of translucency.

PMID- 29368383
TI  - Clinical and cytogenomic findings in OAV spectrum.
AB  - The oculoauriculovertebral spectrum (OAVS) is characterized by anomalies
      involving the development of the first and second pharyngeal arches during the
      embryonic period. The phenotype is highly heterogeneous, involving ears, eyes,
      face, neck, and other systems and organs. There is no agreement in the literature
      for the minimum phenotypic inclusion criteria, but the primary phenotype involves
      hemifacial microsomia with facial asymmetry and microtia. Most cases are sporadic
      and the etiology of this syndrome is not well known. Environmental factors,
      family cases that demonstrate Mendelian inheritance, such as preauricular
      appendages, microtia, mandibular hypoplasia, and facial asymmetry; chromosomal
      abnormalities and some candidate genes suggest a multifactorial inheritance
      model. We evaluated clinical, cytogenomic and molecularly 72 patients with OAVS,
      and compared our findings with patients from the literature. We found 15 CNVs
      (copy number variations) considered pathogenic or possibly pathogenic in 13 out
      of 72 patients. Our results did not indicated a single candidate genomic region,
      but recurrent chromosomal imbalances were observed in chromosome 4 and 22, in
      regions containing genes relevant to the OAVS phenotype or related to known OMIM
      diseases suggesting different pathogenic mechanisms involved in this genetically
      and phenotypic heterogeneous spectrum.

PMID- 29368384
TI  - Relationship between meaningful work and job performance in nurses.
AB  - AIMS: The present study was designed to determine the relationship between
      meaningful work and job performance, and the impact of meaningful work on nursing
      care quality. BACKGROUND: Meaningful work has been suggested as a significant
      factor affecting job performance, but the relationship has never been studied in
      nurses in China. DESIGN: A descriptive correlational study was designed to assess
      the level of meaningful work, tasks, and contextual performance as well as their
      relationships. METHODS: We used a stratified random-sampling approach to enrol
      nurses from hospitals. Multivariate regression analysis was applied to determine
      the relationship between meaningful work and their demographic data. RESULTS:
      There were significant, positive relationships between meaningful work and task
      performance and contextual performance. Education level, work unit, and
      employment type influenced meaningful work. The work motivation score of the
      nurses was lower than that of the other 2 dimensions, and a negative work
      motivation score negatively influenced job performance. CONCLUSION: Improving
      meaningful work and providing more support and assistance could improve nurse
      performance, thereby improving the quality of nursing care.

PMID- 29368385
TI  - Erectile dysfunction in cirrhosis is impacted by liver dysfunction, portal
      hypertension, diabetes and arterial hypertension.
AB  - BACKGROUND: Although several risk factors for erectile dysfunction may be present
      in patients with cirrhosis, data on the actual prevalence and cause of erectile
      dysfunction is limited. The International Index of Erectile Function-5 (IIEF-5)
      is a well-validated survey to determine the presence and severity of erectile
      dysfunction in men. We assessed (i) the prevalence and severity of erectile
      dysfunction, and (ii) risk factors for erectile dysfunction in patients with
      cirrhosis. METHODS: In this prospective study, erectile dysfunction was defined
      as: absent (>21 IIEF-5-points), mild (12-21) and severe (5-11). Patients with
      overt hepatic encephalopathy, active alcohol abuse, extrahepatic malignancy,
      previous urologic surgery, previous liver transplantation and severe cardiac
      conditions were excluded. RESULTS: Among n = 151 screened patients, n = 41 met
      exclusion criteria and n = 30 were sexually inactive. Thus, a final number of n =
      80 male patients with cirrhosis were included. Patient characteristics: age: 53
      +/- 9 years; model for end-stage liver disease score (MELD): 12.7 +/- 3.9; Child
      Pugh score (CPS) A: 30 (37.5%), B: 35 (43.8%), C: 15 (18.7%); alcohol: 38
      (47.5%), viral: 25 (31.3%), alcohol/viral: 7 (8.8%) and others: 10 (12.5%). The
      presence of erectile dysfunction was found in 51 (63.8%) patients with 44 (55%)
      and 7 (8.8%) suffering from mild-to-moderate and moderate-to-severe erectile
      dysfunction. Mean MELD and hepatic venous pressure gradient (HVPG) were
      significantly higher in patients with erectile dysfunction (P = .021; P = .028).
      Child-Pugh score C, MELD, creatinine, age, arterial hypertension, diabetes, low
      libido, low testosterone and high HVPG were associated with the presence of
      erectile dysfunction. Interestingly, beta-blocker therapy was not associated with
      an increased risk. In multivariate models, arterial hypertension (OR: 6.36 [1.16
      34.85]; P = .033), diabetes (OR: 7.40 [1.31-41.75]; P = .023), MELD (OR: 1.19
      [1.03-1.36]; P = .015) and increasing HVPG (n = 48; OR: 1.11 [1.002-1.23]; P =
      .045) were independent risk factors for the presence of erectile dysfunction.
      CONCLUSION: About two-thirds of male patients with cirrhosis show erectile
      dysfunction. Severity of liver dysfunction, portal hypertension, arterial
      hypertension and diabetes were identified as risk factors for erectile
      dysfunction.

PMID- 29368386
TI  - Extreme environments and the origins of biodiversity: Adaptation and speciation
      in sulphide spring fishes.
AB  - Organisms adapted to physiochemical stressors provide ideal systems to study
      evolutionary mechanisms that drive adaptation and speciation. This review study
      focuses on livebearing fishes of the Poecilia mexicana species complex
      (Poeciliidae), members of which have repeatedly colonized hydrogen sulphide (H2
      S)-rich springs. H2 S is a potent respiratory toxicant that creates extreme
      environmental conditions in aquatic ecosystems. There is also a rich history of
      research on H2 S in toxicology and biomedicine, which has facilitated the
      generation of a priori hypotheses about the proximate mechanisms of adaptation.
      Testing these hypotheses through the application of high-throughput genomic and
      transcriptomic analyses has led to the identification of the physiological
      underpinnings mediating adaptation to H2 S-rich environments. In addition,
      systematic natural history studies have provided a nuanced understanding of how
      the presence of a physiochemical stressor interacts with other sources of
      selection to drive evolutionary change in a variety of organismal traits,
      including physiology, morphology, behaviour and life history. Adaptation to
      extreme environments in P. mexicana also coincides with ecological speciation,
      and evolutionarily independent lineages span almost the full range of the
      speciation continuum from panmixia to complete reproductive isolation. Multiple
      mechanisms of reproductive isolation are involved in reducing gene flow between
      adjacent populations that are adapted to contrasting environmental conditions.
      Comparative studies among evolutionarily independent lineages within the P.
      mexicana species complex and, more recently, other members of the family
      Poeciliidae that have colonized H2 S-rich environments will provide insights into
      the factors facilitating or impeding convergent evolution, providing tangible
      links between micro-evolutionary processes and macro-evolutionary patterns.

PMID- 29368387
TI  - The impact of acquired thrombocytopenia on long-term outcomes of patients
      undergoing elective percutaneous coronary intervention: An analysis of 8,271
      consecutive patients.
AB  - BACKGROUND: Acquired thrombocytopenia is associated with an increased risk of
      adverse events of patients with acute coronary syndrome. However, data on its
      long-term prognostic significance are limited. The aim of our study was to
      investigate the association between acquired thrombocytopenia and long-term
      clinical outcomes. METHODS: We examined 8,271 consecutive patients who underwent
      elective percutaneous coronary intervention (PCI) at Fuwai Hospital from January
      2013 to December 2013. Acquired thrombocytopenia was defined as a platelet count
      of <150 * 109 /L after PCI with a normal baseline value. The primary outcomes
      were death and major adverse cardiovascular events (MACEs) during a 30-month
      follow-up. Logistic regression was performed to identify independent predictors
      of acquired thrombocytopenia post-PCI. RESULTS: At the 30-month follow-up,
      acquired thrombocytopenia developed in 654 (7.91%) patients (634 [7.67%] patients
      had mild thrombocytopenia, 20 [0.24%] patients had moderate or severe
      thrombocytopenia). Patients who developed thrombocytopenia had a higher 30-month
      rate of all-cause death (2.3% vs. 1%, P = 0.0086) and cardiogenic death (1.2% vs.
      0.5%, P = 0.0261) than patients who did not develop thrombocytopenia. Moderate or
      severe thrombocytopenia was associated with a 13-fold increased risk for
      cardiogenic death (adjusted HR: 13.578; 95% CI: 1.812-101.75) and 11-fold
      increased risk for myocardial infarction (adjusted HR: 11.309; 95% CI: 2.749
      46.53) compared with patients without thrombocytopenia. Baseline creatinine
      clearance (odds ratio [OR]: 0.993; 95% CI: 0.989-0.996), baseline platelet count
      (OR: 0.924; 95% CI: 0.918-0.93) and diabetes mellitus history (OR: 1.283, 95% CI:
      1.056-1.558) independently predicted acquired thrombocytopenia. CONCLUSIONS:
      Acquired thrombocytopenia was independently associated with long-term adverse
      outcomes. Predictors of thrombocytopenia were baseline creatinine clearance,
      baseline platelet count, and diabetes mellitus history.

PMID- 29368388
TI  - The world-wide incidence of Kaposi's sarcoma in the HIV/AIDS era.
AB  - OBJECTIVES: Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of
      endothelial origin typically occurring in the context of immunosuppression or
      immunodeficiency. Consequently, KS is one of the most common cancers in HIV
      infected individuals and frequently occurs among transplant recipients.
      Nevertheless, its incidence in different populations is not well understood.
      METHODS: We searched online databases for publications on KS incidence. A random
      effect meta-analysis was performed to combine the KS incidences and incidence
      rate ratios (IRRs) for associated risk factors. RESULTS: Seventy-six eligible
      studies representing 71 time periods were included. For HIV-infected people, the
      overall KS incidence was 481.54 per 100 000 person-years with a 95% confidential
      interval (CI) of 342.36-677.32 per 100 000 person-years. HIV-infected men who
      have sex with men (MSM) had the highest incidence of KS (1397.11 per 100 000
      person-years; 95% CI 870.55-2242.18 per 100 000 person-years). The incidence of
      KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI
      1.70-5.62). People receiving highly active antiretroviral therapy (HAART) had a
      lower incidence compared with people who had never received HAART (IRR 6.57; 95%
      CI 1.91-24.69). The incidence of KS was 68.59 (95% CI 31.39-149.86) per 100 000
      person-years in transplant recipients, 52.94 (95% CI 39.90-70.20) per 100 000
      person-years in children with HIV infection, and 1.53 (95% CI 0.33-7.08) per 100
      000 person-years in the general population. CONCLUSIONS: Globally, a relatively
      high incidence of KS was found among HIV-seropositive people and, in particular,
      in HIV-infected MSM. The introduction of HAART has largely prevented the
      development of KS, but it has not entirely removed the challenge of KS. In
      Africa, in particular, KS imposes a very heavy disease burden, which can mainly
      be attributed to the high prevalence of KS-associated herpesvirus and poor access
      to HAART.

PMID- 29368390
TI  - Dermoscopic features of pilar leiomyomas.

PMID- 29368389
TI  - Volumetric modulated arc therapy for total body irradiation: A feasibility study
      using Pinnacle3 treatment planning system and Elekta AgilityTM linac.
AB  - A study was undertaken to explore the use of volumetric modulated arc therapy
      (VMAT) for total body irradiation (TBI). Five patient plans were created in
      Pinnacle3 using nine 6 MV photon dynamic arcs. A dose of 12 Gy in six fractions
      was prescribed. The planning target volume (PTV) was split into four subsections
      for the head, chest, abdomen, and pelvis. The head and chest beams were optimized
      together, followed by the abdomen and pelvis beams. The last stage of the
      planning process involved turning all beams on and performing a final
      optimization to achieve a clinically acceptable plan. Beam isocenters were
      shifted by 3 or 5 mm in the left-right, anterior-posterior, and superior-inferior
      directions to simulate the effect of setup errors on the dose distribution.
      Treatment plan verification consisted of ArcCheck measurements compared to
      calculated doses using a global 3%/3 mm gamma analysis. All five patient plans
      achieved the planning aim of delivering 12 Gy to at least 90% of the target. The
      mean dose in the PTV was 12.7 Gy. Mean lung dose was restricted to 8 Gy, and a
      dose reduction of up to 40% for organs such as the liver and kidneys proved
      feasible. The VMAT technique was found to be sensitive to patient setup errors
      particularly in the superior-inferior direction. The dose predicted by the
      planning system agreed with measured doses and had an average pass rate of 99.2%
      for all arcs. VMAT was found to be a viable treatment technique for total body
      irradiation.

PMID- 29368392
TI  - Response to phenotypic hetergeneity of POMT2 variants.

PMID- 29368393
TI  - Resistance exercise and episodic memory function: a systematic review.
AB  - OBJECTIVE: Emerging research demonstrates that aerobic-based physical activity is
      favourably associated with episodic memory function. Despite resistance exercises
      being associated with a multitude of health outcomes, independent of aerobic
      physical activity, less research has examined the effects of resistance exercise
      on episodic memory function. The purpose of this study was to conduct a
      systematic review to examine the extent to which resistance exercise may be
      associated with episodic memory function. METHODS: Computerized searches were
      performed in PubMed, PsychInfo and Sports Discuss. Studies were included if they
      employed an experimental, cross-sectional or prospective study design, and
      included acute or chronic resistance exercise as the independent variable, with
      episodic memory function as the outcome variable. RESULTS: Eight experimental
      (one acute and seven chronic training studies) studies met the study inclusionary
      criteria. Seven of these studies were published in the last 5 years, highlighting
      the infancy of this line of research. Only three of the eight evaluated studies
      provided evidence of a positive effect of resistance exercise on memory function;
      within each of these three studies, there was also some indication of null (or
      unfavourable) effects. CONCLUSION: The findings of this systematic review do not
      provide compelling evidence for a beneficial effect of acute or chronic
      resistance exercise on episodic memory function. Additional research in this
      under-investigated field is warranted.

PMID- 29368391
TI  - Motivation to reduce alcohol consumption and subsequent attempts at reduction and
      changes in consumption in increasing and higher-risk drinkers in England: a
      prospective population survey.
AB  - AIMS: To assess how far motivation to reduce alcohol consumption in increasing
      and higher-risk drinkers in England predicts self-reported attempts to reduce
      alcohol consumption and changes in alcohol intake during the following 6 months.
      METHODS: This study used self-reported data from 2928 higher-risk drinkers in the
      Alcohol Toolkit Study (ATS): a series of monthly cross-sectional household
      surveys of adults aged 16+ years of age in England. Alcohol consumption was
      measured in an initial survey and in a 6-month telephone follow-up interview
      using the Alcohol Use Disorders Identification Test (AUDIT)-C questionnaire.
      Motivation was measured in the initial survey using the Motivation to Reduce
      Alcohol Consumption (MRAC) scale. Attempts to reduce alcohol consumption during
      the past 6 months were recorded at follow-up. Data were analysed using repeated
      measures difference-in-differences and logistic regression models. RESULTS:
      Participants with higher initial motivation to reduce alcohol consumption were
      more likely to report that they had made an attempt to reduce consumption at
      follow-up [adjusted odds ratio (ORadj ) = 2.39, 95% confidence interval (CI) =
      1.75-3.29]. There was an overall reduction in alcohol consumption between initial
      survey and follow-up (ORadj  = 0.72, 95% CI = 0.65-0.79), but there was
      insufficient evidence of an additional effect of motivation to reduce consumption
      on subsequent changes in alcohol consumption, with the difference-in-differences
      effect instead suggesting an average increase (ORadj  = 1.37, 95% CI = 1.00
      1.88). CONCLUSIONS: Increasing and higher-risk drinkers in England who report
      greater motivation to reduce their consumption are more likely to report making
      an attempt to reduce during the next 6 months, but this may not be associated
      with a reduction in alcohol consumption.

PMID- 29368394
TI  - Complex coronary bifurcation treatment by a novel stenting technique: Bench test,
      fluid dynamic study and clinical outcomes.
AB  - OBJECTIVES: We assess the mid-term outcomes of ultrathin biodegradable polymer
      double stenting using a very minimal crushing (Nano-Crush) technique in large
      complex coronary bifurcation. BACKGROUND: Complex bifurcations have been
      suggested to be better approached by a planned double stent technique. METHODS:
      Two hundred and five consecutive patients (107 males and 98 females) referred for
      large complex coronary bifurcation percutaneous coronary interventions were
      enrolled. The technique was also evaluated by both a bench test with a silicon
      tubes phantom resembling a coronary bifurcation and a computed fluid dynamic
      (CFD) analysis. RESULTS: Left main bifurcation accounted for 40.9% of cases (84
      patients). Mean angles between main branch (MB) and side branch (SB) were 63.6 +/
      21.3 degrees . SB intravascular ultrasound-calculated MSA was 5.6 +/- 1.5 mm2 .
      Clinical follow-up was available for 100% of patients and at a mean follow-up of
      16.2 +/- 6.7 months 8 deaths, all due to cardiovascular reason, (3.9%, 4 patients
      for stroke, two for heart failure, one after surgical aortic valve substitution,
      and one after acute massive pulmonary embolism) and no presumptive stent
      thrombosis or target vessel induced ischemia were observed. Angiographic follow
      up was available in 108 patients (52.7%) and showed a very low significant
      restenosis (5 patients, 4.6%). Bench study and CFD evaluation suggested a
      complete coverage of the SB ostium with a very high strut-free area at the SB.
      CONCLUSIONS: The revascularization of complex large coronary bifurcation disease
      using the Nano-crush technique appeared promising thanks to the favorable fluid
      dynamic profile, complete coverage of the SD ostium, and very small metal amount
      at the carina.

PMID- 29368395
TI  - The role of aggression-related early maladaptive schemas and schema modes in
      aggression in a prisoner sample.
AB  - Contemporary social-cognitive aggression theory and extant empirical research
      highlights the relationship between certain Early Maladaptive Schemas (EMSs) and
      aggression in offenders. To date, the related construct of schema modes, which
      presents a comprehensive and integrated schema unit, has received scant empirical
      attention. Furthermore, EMSs and schema modes have yet to be examined
      concurrently with respect to aggressive behavior. This study examined
      associations between EMSs, schema modes, and aggression in an offender sample.
      Two hundred and eight adult male prisoners completed self-report psychological
      tests measuring their histories of aggression, EMSs, and schema modes. Regression
      analyses revealed that EMSs were significantly associated with aggression but did
      not account for a unique portion of variance once the effects of schema modes
      were taken into account. Three schema modes, Enraged Child, Impulsive Child, and
      Bully and Attack, significantly predicted aggression. These findings support the
      proposition that schema modes characterized by escalating states of anger, rage,
      and impulsivity characterize aggressive offenders. In this regard, we call
      attention to the need to include schema modes in contemporary social-cognitive
      aggression theories, and suggest that systematic assessment and treatment of
      schema modes has the potential to enhance outcomes with violent offenders.

PMID- 29368396
TI  - Elytra Absorb Ultraviolet Radiation but Transmit Infrared Radiation in
      Neotropical Canthon Species (Coleoptera, Scarabaeinae).
AB  - Strategies to deal with global radiation may be related to important aspects of
      species biology and ecology by reflecting, transmitting or absorbing the
      radiation of varying wavelengths differently. The elytra capacity to manage
      infrared, visible and ultraviolet radiations (from 185 to 1400 nm) was assessed
      with a spectrophotometric analysis in five Canthon species of dung beetles; we
      calculated the reflectance, transmittance and absorbance capacity of the elytra
      of these species. These species have different ecologies: two species
      preferentially inhabit forest areas (Canthon angularis and Canthon lividus
      lividus), two species preferentially inhabit open areas (Canthon chalybaeus and
      Canthon tetraodon) including agricultural crops, and one species does not present
      a clear habitat preference and can be found in both habitats (Canthon
      quinquemaculatus). All the species show a similar pattern in which the light from
      shorter wavelengths and higher frequencies is almost entirely absorbed by the
      elytra, while radiation from longer wavelengths and lower frequencies can mostly
      pass through the elytra. However, C. quinquemaculatus seems to have significantly
      higher rates of reflectance and transmittance in the visible- and near-infrared
      spectrum. This different pattern found in C. quinquemaculatus may be associated
      with its capacity to establish populations both in agricultural and forest areas.

PMID- 29368398
TI  - 'Get an early check - Chrysanthemum tea': An outcome evaluation of a multimedia
      campaign promoting HIV testing among men who have sex with men in Hong Kong.
AB  - OBJECTIVES: 'Get an early check - chrysanthemum tea' was a multimedia campaign
      promoting HIV testing targeting Chinese-speaking men who have sex with men (MSM)
      in Hong Kong, China. It ran from October to December 2015. This study was carried
      out to investigate the level of campaign exposure among Chinese-speaking MSM in
      Hong Kong and the association between uptake of HIV testing in the last 6 months
      and campaign exposure. METHODS: A cross-sectional survey was conducted 6 months
      after the campaign was launched. Participants were Hong Kong Chinese-speaking men
      aged >=18 years who had had anal or oral sex with at least one man in their
      lifetime. A total of 153 eligible participants completed the anonymous self
      administered questionnaire. RESULTS: Among the participants, 45.8% had been
      exposed to the campaign and 43.1% had taken up HIV testing in the last 6 months.
      In multivariate logistic regression analysis, exposure to the campaign
      [multivariate odds ratio (ORm) 2.55; 95% confidence interval (CI) 1.25, 5.19] and
      having had anal intercourse with a nonregular sex partner (ORm 2.36; 95% CI 1.05,
      5.31) in the last 6 months were significantly associated with uptake of HIV
      testing in the last 6 months. CONCLUSIONS: The campaign had relatively good reach
      in the target population and may have been useful to encourage them to take up
      HIV testing. Future campaigns promoting HIV testing among MSM in Hong Kong are
      still needed. Such programmes should consider making use of viral videos, having
      a longer project duration and developing culturally sensitive materials for non
      Chinese-speaking MSM.

PMID- 29368397
TI  - l-arginine ingestion inhibits eccentric contraction-induced proteolysis and force
      deficit via S-nitrosylation of calpain.
AB  - It has been shown that calpains are involved in the proteolysis of muscle
      proteins that occurs with eccentric contraction (ECC) and that exogenously
      applied nitric oxide decreases the calpain-mediated proteolysis. The aim of this
      study was to examine the effects of ingestion of l-arginine (ARG), a nitric oxide
      precursor, on ECC-related calpain activation. In the first and second
      experiments, male Wistar rats were given ARG in water for 7 days starting from 3
      days before the ECC protocol (average ingestion, ~600 mg kg-body wt-1  day-1 ).
      Tibialis anterior muscles underwent 200 repeated ECCs and, subsequently, were
      excised 3 days later. Whole muscle analyses (the first experiment) revealed that
      ARG attenuated ECC-induced force deficit and autolysis of calpain-1, and
      increased the amounts of S-nitrosylated calpain-1. Regarding ryanodine receptor
      (RyR) and dihydropyridine receptor (DHPR), ECC-induced proteolysis was completely
      inhibited by ARG, whereas the inhibition was partial for junctophilin-1 (JP1).
      Skinned fiber analyses (the second experiment) showed that ARG also inhibited ECC
      elicited reductions in the ratio of depolarization-induced to maximum Ca2+ 
      activated force. In the third experiment, homogenates of rested muscles were
      treated with S-nitrosylating agent, S-nitrosoglutathione (GSNO), and/or high Ca2+
      concentration ([Ca2+ ]). Treatment with high [Ca2+ ] and without GSNO produced
      proteolysis of RyR, DHPR, and JP1. On the other hand, treatment with high [Ca2+ ]
      and GSNO caused complete inhibition of RyR and DHPR proteolysis and partial
      inhibition of JP1 proteolysis. These results indicate that ARG ingestion can
      attenuate ECC-induced proteolysis of Ca2+ regulatory proteins and force deficit
      by decreasing calpain activation via S-nitrosylation.

PMID- 29368399
TI  - Do interindividual differences in cardiac output during submaximal exercise
      explain differences in exercising muscle oxygenation and ratings of perceived
      exertion?
AB  - Considerable interindividual differences in the Q-VO2 relationship during
      exercise have been documented but implications for submaximal exercise tolerance
      have not been considered. We tested the hypothesis that these interindividual
      differences were associated with differences in exercising muscle deoxygenation
      and ratings of perceived exertion (RPE) across a range of submaximal exercise
      intensities. A total of 31 (21 +/- 3 years) healthy recreationally active males
      performed an incremental exercise test to exhaustion 24 h following a resting
      muscle biopsy. Cardiac output (Q L/min; inert gas rebreathe), oxygen uptake (VO2
      L/min; breath-by-breath pulmonary gas exchange), quadriceps saturation (near
      infrared spectroscopy) and exercise tolerance (6-20; Borg Scale RPE) were
      measured. The Q-VO2 relationship from 40 to 160 W was used to partition
      individuals post hoc into higher (n = 10; 6.3 +/- 0.4) versus lower (n = 10; 3.7
      +/- 0.4, P < 0.001) responders. The Q-VO2 difference between responder types was
      not explained by arterial oxygen content differences (P = 0.5) or peripheral
      skeletal muscle characteristics (P from 0.1 to 0.8) but was strongly associated
      with stroke volume (P < 0.05). Despite considerable Q-VO2 difference between
      groups, no difference in quadriceps deoxygenation was observed during exercise
      (all P > 0.4). Lower cardiac responders had greater leg (P = 0.027) and whole
      body (P = 0.03) RPE only at 185 W, but this represented a higher %peak VO2 in
      lower cardiac responders (87 +/- 15% vs. 66 +/- 12%, P = 0.005). Substantially
      lower Q-VO2 in the lower responder group did not result in altered RPE or
      exercising muscle deoxygenation. This suggests substantial recruitment of blood
      flow redistribution in the lower responder group as part of protecting matching
      of exercising muscle oxygen delivery to demand.

PMID- 29368400
TI  - Cerebrospinal fluid HIV RNA in persons living with HIV.
AB  - OBJECTIVES: Despite adequate suppression of plasma HIV RNA, viral escape in
      cerebrospinal fluid (CSF) is widely reported. Rates of CSF HIV RNA escape vary in
      the literature. In persons living with HIV (PLWH) undergoing lumbar puncture
      examination for clinical reasons, we assessed rates of CSF HIV RNA escape.
      METHODS: Persons living with HIV attending a designated HIV neurology service
      undergoing CSF assessment for clinical reasons between January 2015 and April
      2017 were included in the study. CSF HIV RNA escape was defined as HIV RNA >= 0.5
      log10 HIV-1 RNA copies/mL higher than plasma HIV RNA or detectable CSF HIV RNA
      when plasma HIV RNA was < 20 copies/mL. Clinical factors associated with CSF HIV
      RNA were assessed using logistic regression modelling. RESULTS: Of 38
      individuals, 35 were receiving antiretroviral therapy, 30 were male and their
      mean age was 51 years. Clinical reasons for CSF assessment included investigation
      for cognitive decline (n = 25), early syphilis (n = 4) and other central nervous
      system (CNS) conditions (n = 9). HIV RNA was detectable in plasma and CSF in
      seven and six individuals, respectively, with two individuals (5.3%) meeting the
      definition of CSF escape. Detectable CSF HIV RNA was associated with a detectable
      plasma HIV RNA (P < 0.001) and a history of known antiretroviral drug resistance
      mutations (P = 0.021). CONCLUSIONS: The prevalence of CSF viral escape in PLWH
      undergoing lumbar puncture examination for clinical reasons is lower than
      previously reported.

PMID- 29368401
TI  - Patient perspectives on de-simplifying their single-tablet co-formulated
      antiretroviral therapy for societal cost savings.
AB  - OBJECTIVES: The incremental costs of expanding antiretroviral (ARV) drug
      treatment to all HIV-infected patients are substantial, so cost-saving
      initiatives are important. Our objectives were to determine the acceptability and
      financial impact of de-simplifying (i.e. switching) more expensive single-tablet
      formulations (STFs) to less expensive generic-based multi-tablet components. We
      determined physician and patient perceptions and acceptance of STF de
      simplification within the context of a publicly funded ARV budget. METHODS:
      Programme costs were calculated for patients on ARVs followed at the Southern
      Alberta Clinic, Canada during 2016 (Cdn$). We focused on patients receiving
      Triumeq(r) and determined the savings if patients de-simplified to eligible
      generic co-formulations. We surveyed all prescribing physicians and a convenience
      sample of patients taking Triumeq(r) to see if, for budgetary purposes, they felt
      that de-simplification would be acceptable. RESULTS: Of 1780 patients receiving
      ARVs, 62% (n = 1038) were on STF; 58% (n = 607) of patients on STF were on
      Triumeq(r). The total annual cost of ARVs was $26 222 760. The cost for
      Triumeq(r) was $8 292 600. If every patient on Triumeq(r) switched to generic
      abacavir/lamivudine and Tivicay(r) (dolutegravir), total costs would decrease by
      $4 325 040. All physicians (n = 13) felt that de-simplifying could be safely
      achieved. Forty-eight per cent of 221 patients surveyed were agreeable to de
      simplifying for altruistic reasons, 27% said no, and 25% said maybe. CONCLUSIONS:
      De-simplifying Triumeq(r) generates large cost savings. Additional savings could
      be achieved by de-simplifying other STFs. Both physicians and patients agreed
      that selective de-simplification was acceptable; however, it may not be
      acceptable to every patient. Monitoring the medical and cost impacts of de
      simplification strategies seems warranted.

PMID- 29368402
TI  - Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex
      Drug-Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects.
AB  - This study aimed to construct a physiologically based pharmacokinetic (PBPK)
      model of rifampicin that can accurately and quantitatively predict complex drug
      drug interactions (DDIs) involving its saturable hepatic uptake and auto
      induction. Using in silico and in vitro parameters, and reported clinical
      pharmacokinetic data, rifampicin PBPK model was built and relevant parameters for
      saturable hepatic uptake and UDP-glucuronosyltransferase (UGT) auto-induction
      were optimized by fitting. The parameters for cytochrome P450 (CYP) 3A and CYP2C9
      induction by rifampicin were similarly optimized using clinical DDI data with
      midazolam and tolbutamide as probe substrates, respectively. For validation, our
      current PBPK model was applied to simulate complex DDIs with glibenclamide (a
      substrate of CYP3A/2C9 and hepatic organic anion transporting polypeptides
      (OATPs)). Simulated results were in quite good accordance with the observed data.
      Altogether, our constructed PBPK model of rifampicin demonstrates the robustness
      and utility in quantitatively predicting CYP3A/2C9 induction-mediated and/or OATP
      inhibition-mediated DDIs with victim drugs.

PMID- 29368403
TI  - Cortical contributions to anticipatory postural adjustments in the trunk.
AB  - KEY POINTS: Increases in activity of trunk muscles that occur prior to, or
      concurrent with, a voluntary limb movement are termed anticipatory postural
      adjustments (APAs). APAs are important for maintaining postural stability in
      response to perturbations but the neural mechanisms underlying APAs remain
      unclear. Our results showed that corticospinal excitability of erector spinae
      (ES) muscle increased at 40 ms prior to rapid shoulder flexion, with a reduction
      in intracortical inhibition and no change in spinal excitability. Changes in
      corticospinal excitability were observed in ES, with similar excitability
      profiles between standing and lying positions, but were not observed in rectus
      abdominis. We suggest that the neural control of postural adjustments involves
      changes at a cortical level, which in part are due to reduced inhibition.
      ABSTRACT: Voluntary limb movements are associated with increases in trunk muscle
      activity, some of which occur within a time window considered too fast to be
      induced by sensory feedback; these increases are termed anticipatory postural
      adjustments (APAs). Although it is known that the function of APAs is to maintain
      postural stability in response to perturbations, excitability of the
      corticospinal projections to the trunk muscles during the APAs remains unclear.
      Thirty-four healthy subjects performed rapid shoulder flexion in response to a
      visual cue in standing and lying positions. Transcranial magnetic stimulation
      (TMS) was delivered over the trunk motor cortex to examine motor evoked
      potentials (MEPs) in erector spinae (ES) and in rectus abdominis (RA) muscles at
      several time points prior to the rise in electromyographic activity (EMG) of
      anterior deltoid (AD) muscle. TMS was also used to assess short-interval
      intracortical inhibition (SICI) and cervicomedullary MEPs (CMEPs) in ES in the
      standing position. MEPs in ES were larger at time points closer to the rise in AD
      EMG in both standing and lying positions, whereas MEPs in RA did not differ over
      the time course examined. Notably, SICI was reduced at time points closer to the
      rise in AD EMG, with no change in CMEPs. Our results demonstrate that increasing
      excitability of corticospinal projections to the trunk muscles prior to a
      voluntary limb movement is likely to be cortical in origin and is muscle
      specific.

PMID- 29368404
TI  - Effects of a Peganum harmala (Zygophyllaceae) preparation for root canal
      disinfection.
AB  - The aim of this study was to determine the antimicrobial capacity, minimum
      inhibitory concentration (MIC), and cytotoxic effects of a Peganum harmala seed
      extract in comparison to 5.25% sodium hypochlorite (NaOCl). The oral pathogen
      Enterococcus faecalis was used to evaluate the antimicrobial capacity, and the
      MIC values were determined through serial dilution. Inhibition zones were
      measured in millimeter, and the data were analyzed statistically by analysis of
      variance and the Tukey HSD test. For cytotoxicity testing, P. harmala seed
      extract and 5.25% NaOCl solution were incubated with L929 fibroblast cells. After
      1, 24, and 72 hr of incubation, cells were stained and the optical density
      determined with an enzyme-linked immunosorbent assay (ELISA) reader. Data were
      analyzed with Chi-Square statistical test. The significance level was set at p <
      .05. There was no significant difference between the antimicrobial capacity of
      5.25% NaOCl and the P. harmala extract (p > .05; MIC 4 MUg/ml). The Microculture
      Tetrazolium (MTT) assay test showed that the cytotoxic effects of the P. harmala
      extract were significantly lower than 5.25% NaOCl (p < .05). The results show
      that 5.25% NaOCl and P. harmala seed extract have similar antimicrobial activity
      against Enterococcus faecalis; but P. harmala, which shows reduced cytotoxicity,
      should be considered for further investigation as a safe, phytotherapeutic,
      intracanal irrigant.

PMID- 29368405
TI  - Effects of seed mixture sowing with transgenic Bt rice and its parental line on
      the population dynamics of target stemborers and leafrollers, and non-target
      planthoppers.
AB  - The widespread planting of insect-resistant crops has caused a dramatic shift in
      agricultural landscapes, thus raising concerns about the potential impacts on
      both target and non-target pests. In this study, we examined the potential
      effects of intra-specific seed mixture sowing with transgenic Bt rice (Bt) and
      its parental non-transgenic line (Nt) (100% Bt rice [Bt100 ], 5% Nt+95% Bt [Nt05
      Bt95 ], 10% Nt+90% Bt [Nt10 Bt90 ], 20% Nt+80% Bt [Nt20 Bt80 ], 40% Nt+60% Bt
      [Nt40 Bt60 ] and 100% Nt rice [Nt100 ]) on target and non-target pests in a 2
      year field trial in southern China. The occurrence of target pests, Sesamia
      inferens, Chilo suppressalis and Cnaphalocrocis medinalis, decreased with the
      increased ratio of Bt rice, and the mixture ratios with more than 90% Bt rice
      (Bt100 and Nt05 Bt95 ) significantly increased the pest suppression efficiency,
      with the lowest occurrences of non-target planthoppers, Nilaparvata lugens and
      Sogatella furcifera in Nt100 and Nt05 Bt95 . Furthermore, there were no
      significant differences in 1000-grain dry weight and grain dry weight per 100
      plants between Bt100 and Nt05 Bt95 . Seed mixture sowing of Bt rice with <=10%
      (especially 5%) of its parent line was sufficient to overcome potential
      compliance issues that exist with the use of block or structured refuge to
      provide most effective control of both target and non-target pests without
      compromising the grain yield. It is also expected that the strategy of seed
      mixture sowing with transgenic Bt rice and the non-transgenic parental line would
      provide rice yield stability while decreasing the insecticide use frequency in
      rice production.

PMID- 29368406
TI  - Cultivation of seaweed Gracilaria lemaneiformis enhanced biodiversity in a
      eukaryotic plankton community as revealed via metagenomic analyses.
AB  - Plankton diversity reflects the quality and health of waters and should be
      monitored as a critical feature of marine ecosystems. This study applied a pair
      of 28S rRNA gene-specific primers and pyrosequencing to assess the effects of
      large-scale cultivation of the seaweed Gracilaria lemaneiformis on the
      biodiversity of eukaryotic plankton community in the coastal water of Guangdong,
      China. With 1 million sequences (2,221 operational taxonomic units [OTUs])
      obtained from 51 samples, we found that the biodiversity of eukaryotic plankton
      community was significantly higher in the seaweed cultivation area than that in
      the nearby control area as reflected in OTU richness, evenness (Shannon-Wiener
      index) and dominance (Simpson index) for total plankton community and its four
      subcategories when Gracilaria biomass reached the maximum, while no such a
      significant difference was observed before seaweed inoculation. Our laboratory
      experiment using an artificial phytoplankton community of nine species observed
      the same effects of Gracilaria exposure. Principal component analysis and
      principal coordinates analysis showed the plankton community structure in
      cultivation area markedly differed from the control area when Gracilaria biomass
      reached its maximum. Redundancy analysis showed that G. lemaneiformis was the
      critical factor in controlling the dynamics of eukaryotic plankton communities in
      the studied coastal ecosystem. Our results explicitly demonstrated G.
      lemaneiformis cultivation could enhance biodiversity of plankton community via
      allelopathy, which prevents one or several plankton species from blooming and
      consequently maintains a relatively higher biodiversity. Our study provided
      further support for using large-scale G. lemaneiformis cultivation as an
      effective approach for improving costal ecosystem health.

PMID- 29368407
TI  - The new therapeutic herbal drug HM0601 and its bioactive compound rutin exert
      potent antiproliferative activities in mast cells.
AB  - HM0601 consists of Allium hookeri and Lycium chinense fruit and contains a lot of
      rutin. Here, we ascertained whether HM0601 and its major compound rutin reduce
      proliferation of human mast cell line, HMC-1, under thymic stromal lymphopoietin
      (TSLP) stimulation. Therapeutic rutin or HM0601 treatment considerably reduced
      proliferation of mast cells without exposing activated HMC-1 cells to any
      cytotoxicity. Reduced levels of mouse double minute 2 and phosphorylated signal
      transducers and activators of transcription 6 were accompanied by treatment with
      rutin or HM0601. In TSLP-stimulated cells, rutin or HM0601 treatment
      significantly impaired levels of interleukin (IL)-13 and Bcl2 expression.
      Notably, rutin or HM0601 treatment returned Bax and phosphorylated p53 protein
      levels and caspase-3 activities impaired by TSLP. In addition, levels of
      inflammatory cytokine were considerably reduced by treatment with rutin or HM0601
      on TSLP-stimulated cells. In conclusion, these results indicate that HM0601 can
      be used as a new therapeutic herbal drug for prevention and therapeutic
      intervention of allergic inflammatory diseases.

PMID- 29368408
TI  - Cytotoxicity of Tanshinone IIA combined with Taxol on drug-resist breast cancer
      cells MCF-7 through inhibition of Tau.
AB  - Drug resistance represents a major obstacle to improving the overall response and
      survival of cancer patients. Taxol is one of the most commonly used chemotherapy
      agents in breast cancer. As with many cancer therapeutic agents, resistance
      remains a significant problem when using Taxol to treat malignancies. In this
      study, estrogen receptor positive breast cancer cells MCF-7 were induced Taxol
      resistance. And Tanshinone IIA combined with Taxol was chosen to treat it. The
      drugs combination showed additive effect in most drug concentrations. Drug
      resistance cancer cells showed a higher microtubule associated protein (Tau)
      expression, which was considered as one of the reasons for Taxol resistance.
      Tanshinone IIA inhibited the expression of Tau in MCF-7 cells and resulted in
      higher sensibility of Taxol. Moreover, Tanshinone IIA also showed cytotoxicity to
      MCF-7, which might be related to its estrogenicity effect. In conclusion, the
      combination of Tanshinone IIA and Taxol showed higher cytotoxicity to Taxol
      resistant MCF-7 cells, which might be related to the inhibition of Tau.

PMID- 29368409
TI  - The effect of Banisteriopsis caapi (B. caapi) on the motor deficits in the MPTP
      treated common marmoset model of Parkinson's disease.
AB  - Banisteriopsis caapi (B. caapi) contains harmine, harmaline, and
      tetrahydroharmine, has monoamine oxidase inhibitory activity, and has reported
      antiparkinsonian activity in humans when imbibed as a tea; however, its effects
      are poorly documented. For this reason, motor function was assessed in 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets following
      administration of B. caapi extract (28.4-113.6 mg/kg; po), harmine (0.1 and 0.3
      mg/kg; sc), and selegiline (10 mg/kg; sc), alone or with a submaximal dose of L
      3,4-dihydroxyphenylalanine (L-DOPA; 4-7 mg/kg). L-DOPA reversed motor disability,
      increased locomotor activity, and induced moderate dyskinesia. B. caapi did not
      increase locomotor activity or induce dyskinesia but at 56.8 and 113.6 mg/kg
      improved motor disability. The L-DOPA response was unaltered by co-administration
      of B. caapi. Harmine (0.1 and 0.3 mg/kg) produced a mild improvement in motor
      disability without affecting locomotor activity or dyskinesia but had no effect
      on the L-DOPA-induced antiparkinsonian response. Selegiline (10 mg/kg) alone
      improved motor function to the same extent as L-DOPA, but with only mild
      dyskinesia, and did not alter the response to L-DOPA, although dyskinesia was
      reduced. The findings suggest that B. caapi alone has a mild antiparkinsonian
      effect but does not enhance the L-DOPA response or reduce dyskinesia.

PMID- 29368410
TI  - Recognition of clinical characteristics for population-based surveillance of
      fetal alcohol syndrome.
AB  - BACKGROUND: The diagnosis of fetal alcohol syndrome (FAS) rests on identification
      of characteristic facial, growth, and central nervous system (CNS) features.
      Public health surveillance of FAS depends on documentation of these
      characteristics. We evaluated if reporting of FAS characteristics is associated
      with the type of provider examining the child. METHODS: We analyzed cases aged 7
      9 years from the Fetal Alcohol Syndrome Surveillance Network II (FASSNetII). We
      included cases whose surveillance records included the type of provider
      (qualifying provider: developmental pediatrician, geneticist, neonatologist;
      other physician; or other provider) who evaluated the child as well as the FAS
      diagnostic characteristics (facial dysmorphology, CNS impairment, and/or growth
      deficiency) reported by the provider. RESULTS: A total of 345 cases were eligible
      for this analysis. Of these, 188 (54.5%) had adequate information on type of
      provider. Qualifying physicians averaged more than six reported FAS
      characteristics while other providers averaged less than five. Qualifying
      physicians reported on facial characteristics and developmental delay more
      frequently than other providers. Also, qualifying physicians reported on all
      three domains of characteristics (facial, CNS, and growth) in 97% of cases while
      others reported all three characteristics on two thirds of cases. CONCLUSIONS:
      Documentation in medical records during clinical evaluations for FAS is lower
      than optimal for cross-provider communication and surveillance purposes. Lack of
      documentation limits the quality and quantity of information in records that
      serve as a major source of data for public health surveillance systems.

PMID- 29368411
TI  - Dual regulation of decorin by androgen and Hedgehog signaling during prostate
      morphogenesis.
AB  - BACKGROUND: Prostate ductal branching morphogenesis involves a complex
      spatiotemporal regulation of cellular proliferation and remodeling of the
      extracellular matrix (ECM) around the developing ducts. Decorin (Dcn) is a small
      leucine-rich proteoglycan known to sequester several growth factors and to act as
      a tumor suppressor in prostate cancer. RESULTS: Dcn expression in the developing
      prostate paralleled branching morphogenesis and was dynamically regulated by
      androgen and Hedgehog (Hh) signaling. DCN colocalized with collagen in the
      periductal stroma and acellular interstitium. Exogenous DCN decreased epithelial
      proliferation in ex vivo organ cultures of developing prostate, whereas genetic
      ablation of Dcn resulted in increased epithelial proliferation in the developing
      prostate. CONCLUSIONS: Dcn expression and localization in the developing prostate
      is consistent with a primary role in organizing collagen around the developing
      ducts. Regulation of Dcn expression appears to be complex, involving both
      androgen and Hh signaling. The growth inhibitory effect of Dcn suggests a unique
      linkage between a structural proteoglycan and epithelial growth regulation. This
      may serve to coordinate two elements of the morphogenetic process: ductal growth
      and organization of the collagen matrix around the nascent duct. Developmental
      Dynamics 247:679-685, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29368412
TI  - Tuning the Surface Composition of Ni/meso-CeO2 with Iridium as an Efficient
      Catalyst for Hydrogen Generation from Hydrous Hydrazine.
AB  - Selective decomposition of hydrous hydrazine (N2 H4 ?H2 O) over metal catalysts
      provides a promising means for onboard or portable hydrogen source applications.
      Studies on N2 H4 ?H2 O decomposition catalysts mainly focus on the effects of
      bulk composition and structure on their performances, instead of the surface
      composition-dependent properties. Herein, the synthesis of an Ir-modified Ni/meso
      CeO2 catalyst is reported by using a combination of colloidal solution combustion
      synthesis and galvanic replacement methods. A combination of structural
      characterization, control experiments, and DFT calculations reveals that the Ni
      Ir alloy resulting from calcination treatment exerts a profound effect on the
      catalytic properties. The resulting Ni@Ni-Ir/meso-CeO2 catalyst shows excellent
      catalytic performance towards hydrogen generation from N2 H4 ?H2 O, which
      compares favorably with the Ni-Ir bimetallic catalysts reported to date.

PMID- 29368413
TI  - Real-life adaptations in walking patterns in patients with established peripheral
      arterial disease assessed using a global positioning system in the community: a
      cohort study.
AB  - OBJECTIVE: Lower extremity peripheral arterial disease (PAD) is a chronic
      condition most commonly presenting with intermittent claudication (IC).
      Intermittent claudication limits walking ability and may negatively affect health
      related quality of life. Treadmill assessment of maximal walking distance (MWD)
      is the gold standard to assess PAD symptom severity. Despite being a well
      established and reproducible tool, it may be inappropriate (due to frailty or
      fear) for some patients and only describes maximal abilities for a single walk
      test. Global positioning systems (GPS) have been proposed as reliable and
      reproducible tool to measure total, mean and maximal walking distances in
      patients with PAD, in the community setting. Using GPS, our study attempted to
      explore what happens to the walking ability of patients with IC following no
      intervention under 'real-life' conditions. DESIGN AND METHODS: Using the
      GlobalSat DG100 GPS, forty-three patients (69 +/- 9 years; nine female; no
      invasive interventions or rehabilitation) undertook two 60-min walking
      assessments, 6 months apart. Assessments took place in community spaces that had
      even terrain, no tall trees or buildings and were free from motorized vehicles.
      Global positioning systems-measured maximum walking distance was the main study
      outcome measure. RESULTS: Over the 6-month period, patients demonstrated
      significantly shorter GPS-measured, mean (552 m versus 334 m; P = 0.02) and
      maximum (714 m versus 545 m; P = 0.04) walking distances, stopping also more
      frequently (nine versus five times; P = 0.03). CONCLUSIONS: Given the reported
      symptom progression, we advocate early intervention (e.g. exercise interventions)
      combined with frequent patient monitoring in attempts to maintain or improve
      walking ability.

PMID- 29368414
TI  - Stromal tiny black dots, like "sugar-coated", of von Kossa stain is a diagnostic
      clue to hyalinizing trabecular tumor of the thyroid gland.
AB  - Hyalinizing trabecular tumor (HTT) is a rare low-grade tumor, and a prominent
      feature is the basement membranous stroma. We assume that such characteristic
      stromal findings of HTT are related to calcium deposition, and examined HTT
      samples by von Kossa special staining. There has been no report describing von
      Kossa special staining for such stroma. We collected 12 cases of HTT and 30 cases
      of papillary thyroid carcinoma (PTC) that had matched age, gender, tumor size,
      and surgical procedure characteristics as a control group. We compared the
      staining pattern and degree of von Kossa positivity between HTT and PTC, and a
      grading system of von Kossa stain was adopted to highlight differences between
      them. On von Kossa staining, all HTT revealed many tiny black dots around vessels
      in the hyalinized stroma, like "sugar-coated", and a high degree of calcium
      deposition in most cases, whereas PTC showed sparse stromal calcification in some
      cases. The degree of von Kossa staining was significantly different between the
      two groups. This is the first report describing abundant tiny black dots, like a
      "sugar-coated" appearance, of von Kossa stain in HTT. Here, we propose this
      finding can be a useful diagnostic clue to HTT.

PMID- 29368415
TI  - Sleep-disordered breathing in hypertensive disorders of pregnancy: a BMI-matched
      study.
AB  - Sleep-disordered breathing is more common in hypertensive disorders during
      pregnancy; however, most studies have not adequately accounted for the potential
      confounding impact of obesity. This study evaluated the frequency of sleep
      disordered breathing in women with gestational hypertension and pre-eclampsia
      compared with body mass index- and gestation-matched normotensive pregnant women.
      Women diagnosed with gestational hypertension or pre-eclampsia underwent
      polysomnography shortly after diagnosis. Normotensive controls body mass index
      matched within +/-4 kg m-2 underwent polysomnography within +/-4 weeks of
      gestational age of their matched case. The mean body mass index and gestational
      age at polysomnography were successfully matched for 40 women with gestational
      hypertension/pre-eclampsia and 40 controls. The frequency of sleep-disordered
      breathing in the cases was 52.5% compared with 37.5% in the control group (P =
      0.18), and the respiratory disturbance index overall did not differ (P = 0.20).
      However, more severe sleep-disordered breathing was more than twice as common in
      women with gestational hypertension or pre-eclampsia (35% versus 15%, P = 0.039).
      While more than half of women with a hypertensive disorder of pregnancy meet the
      clinical criteria for sleep-disordered breathing, it is also very common in
      normotensive women of similar body mass index. This underscores the importance of
      adjusting for obesity when exploring the relationship between sleep-disordered
      breathing and hypertension in pregnancy. More severe degrees of sleep-disordered
      breathing are significantly associated with gestational hypertension and pre
      eclampsia, and sleep-disordered breathing may plausibly play a role in the
      pathophysiology of pregnancy hypertension in these women. This suggests that more
      severe sleep-disordered breathing is a potential therapeutic target for reducing
      the prevalence or severity of hypertensive disorders in pregnancy.

PMID- 29368416
TI  - Presymptomatic screening for autoimmune beta-cell disorder: Baby steps toward
      prevention?

PMID- 29368417
TI  - Continuing education: online monitoring of haemodialysis dose.
AB  - BACKGROUND: Kt/Vurea reflects the efficacy of haemodialysis scaled to patient
      size (urea distribution volume). The guidelines recommend monthly Kt/V
      measurements based on blood samples. Modern haemodialysis machines are equipped
      with accessories monitoring the dose online at every session without extra costs,
      blood samples and computers. OBJECTIVE: To describe the principles, devices,
      benefits and shortcomings of online monitoring of haemodialysis dose. DESIGN: A
      critical literature overview and discussion. RESULTS: UV absorbance methods
      measure Kt/V, ionic dialysance Kt (product of clearance and treatment time;
      cleared volume without scaling). Both are easy and useful methods, but comparison
      is difficult due to problems in scaling of the dialysis dose to the patient's
      size. CONCLUSIONS: The best dose estimation method is the one which predicts the
      quality of life and survival most accurately. There is some evidence on the
      predictive value of ionic dialysance Kt, but more documentation is required on
      the UV method. Online monitoring is a useful tool in everyday quality assurance,
      but blood samples are still required for more accurate kinetic modelling.
      LEARNING OUTCOMES: After reading this article the reader should be able to:
      Understand the elements of the Kt/V equation for dialysis dose. Compare and
      contrast different methods of measurement of dialysis dose. Reflect on the
      importance of adequate dialysis dose for patient survival and life quality.

PMID- 29368418
TI  - Ileocolonic neuroendocrine tumours identified in the English bowel cancer
      screening programme.
AB  - AIM: Ileocolonic neuroendocrine tumours (NETs) are diagnosed as part of bowel
      cancer screening programmes (BCSPs). The aim of this study was to identify and
      characterize NETs diagnosed within the English BCSP, a double-screen programme
      that uses guaic faecal occult blood test (gFOBT) screening and colonoscopy, by
      interrogating the national colorectal screening database and validating the
      findings with individual BCSP centres. METHOD: The Exeter database was
      interrogated by running queries to identify participants with coded NETs (from
      the start of the programme in July 2006 - 1 December 2014). A written proforma
      was sent to the responsible BCSP clinician for validation and characterization.
      RESULTS: During this period, 13 061 716 participants were adequately screened
      using gFOBTs, and 259 765 participants had definitively abnormal results. There
      were 146 unique participants with NET-related codes from 216 707 BCSP
      colonoscopies. The diagnosis rates per 100 000 colonoscopies were 29 rectal, 18
      colonic and 11 ileal NETs. The majority of rectal NETs had Grade 1 (80%) and
      Stage T1 (85.1%) disease. Over half of ileal NETs (53.6%) in this study had
      invasive disease, with 85.2% having nodal and 36.1% having metastastatic disease.
      CONCLUSION: The current study highlights the rate of colorectal NETs diagnosed in
      the English BCSP. These data highlight a higher-than-anticipated incidence, and
      the potential additional benefit of BCSPs in identifying occult NETs.

PMID- 29368419
TI  - Utility of single versus multiple breath washout in adult asthma.
AB  - Nitrogen multiple breath washout (N2 MBW) is a sensitive method to identify
      peripheral airway involvement in asthma, but is a time-consuming test. The N2
      vital capacity single breath (VC SBW) test offers greater time efficiency, but
      concordance with N2 MBW is poorly understood. The prevalence of peripheral airway
      abnormality was determined by N2 MBW and N2 SBW tests in 194 asthmatic subjects
      aged 18-1 years. N2 MBW data were related to findings in 400 healthy controls,
      aged 17-71 years, while N2 SBW data were compared to findings in 224 healthy
      controls, aged 15-65 years, to derive equipment-specific reference values.
      Amongst asthmatic subjects, relationships between N2 SBW and N2 MBW outcomes were
      studied. N2 SBW relationship with clinical history, spirometry, blood eosinophils
      and fraction exhaled nitric oxide (FENO) data was also explored. The prevalence
      of peripheral airway involvement (i.e. abnormal ventilation distribution)
      determined by N2 SBW-derived phase III slope (N2 SIII ) was 24.7%, compared to
      44% determined by N2 MBW-derived lung clearance index (LCI) (P<0.001). Predictors
      of abnormal N2 SIII were older age, smoking history and lower FEV1. N2 SBW offers
      lower sensitivity than N2 MBW to detect small airway dysfunction in adult asthma,
      but may be a marker of more severe disease.

PMID- 29368420
TI  - Minimizing dose variation from the interplay effect in stereotactic radiation
      therapy using volumetric modulated arc therapy for lung cancer.
AB  - It is important to improve the magnitude of dose variation that is caused by the
      interplay effect. The aim of this study was to investigate the impact of the
      number of breaths (NBs) to the dose variation for VMAT-SBRT to lung cancer. Data
      on respiratory motion and multileaf collimator (MLC) sequence were collected from
      the cases of 30 patients who underwent radiotherapy with VMAT-SBRT for lung
      cancer. The NBs in the total irradiation time with VMAT and the maximum
      craniocaudal amplitude of the target were calculated. The MLC sequence complexity
      was evaluated using the modulation complexity score for VMAT (MCSv). Static and
      dynamic measurements were performed using a cylindrical respiratory motion
      phantom and a micro ionization chamber. The 1 standard deviation which were
      obtained from 10 dynamic measurements for each patient were defined as dose
      variation caused by the interplay effect. The dose distributions were also
      verified with radiochromic film to detect undesired hot and cold dose spot. Dose
      measurements were also performed with different NBs in the same plan for 16
      patients in 30 patients. The correlations between dose variations and parameters
      assessed for each treatment plan including NBs, MCSv, the MCSv/amplitude quotient
      (TMMCSv), and the MCSv/amplitude quotient * NBs product (IVS) were evaluated.
      Dose variation was decreased with increasing NBs, and NBs of >40 times maintained
      the dose variation within 3% in 15 cases. The correlation between dose variation
      and IVS which were considered NBs was shown stronger (R2  = 0.43, P < 0.05) than
      TMMCSv (R2  = 0.32, P < 0.05). The NBs is an important factor to reduce the dose
      variation. The patient who breathes >40 times during irradiation of two partial
      arcs VMAT (i.e., NBs = 16 breaths per minute) may be suitable for VMAT-SBRT for
      lung cancer.

PMID- 29368421
TI  - Incapacity to control emotion in major depression may arise from disrupted white
      matter integrity and OFC-amygdala inhibition.
AB  - BACKGROUND: Disturbances in emotion regulation are the hallmarks of major
      depressive disorder (MDD). The incapacity to control negative emotion in patients
      has been associated with abnormal hyperactivation of the limbic system and
      hypoactivation of the frontal cortex. The amygdala and orbital frontal cortex
      (OFC) are two critical regions of the emotion regulation neural systems. METHODS:
      This study investigated the anatomical basis of abnormal emotion regulation by
      tracking the fiber tracts connecting the amygdala and OFC. In addition, using
      dynamic casual modeling on resting-state fMRI data of 20 MDD patients and
      equivalent controls, we investigated the exact neural mechanism through which
      abnormal communications between these two nodes were mediated in MDD. KEY
      RESULTS: The results revealed disrupted white matter integrity of fiber tracts in
      MDD, suggesting that functional abnormalities were accompanied by underlying
      anatomical basis. We also detected a failure of inhibition of the OFC on the
      activity of the amygdala in MDD, suggesting dysconnectivity was mediated through
      "top-down" influences from the frontal cortex to the amygdala. Following 8 weeks
      of antidepressant treatment, the patients showed significant clinical improvement
      and normalization of the abnormal OFC-amygdala structural and effective
      connectivity in the left hemisphere. CONCLUSIONS & INFERENCES: Our findings
      suggest that pathways connecting these two nodes may be core targets of the
      antidepressant treatment. In particular, it raised the intriguing question: Does
      the reversal of structural markers of connectivity reflect a response to
      antidepressant medication or activity-dependent myelination following a
      therapeutic restoration of effective connectivity?

PMID- 29368423
TI  - Editorial.

PMID- 29368425
TI  - Genetic assessment wait time indicators in the High Risk Ontario Breast Screening
      Program.
AB  - BACKGROUND: The Ontario Breast Screening Program (OBSP) expanded in July 2011 to
      screen high-risk women aged 30-69 with annual MRI and mammography. This study
      evaluated wait time (WT) indicators along the genetic assessment (GA) pathway for
      women referred to the High Risk OBSP. METHODS: Information was collected for
      27,170 women referred to the High Risk OBSP from July 2011 to June 2015 and
      followed for GA until June 2016. Median duration (days), interquartile range
      (IQR) were measured for each WT indicator by program year, age, prior breast
      cancer, and risk criteria. RESULTS: Among 24,811 women who completed GA, 16,367
      (66.0%) had genetic counseling only, 8,444 (34.0%) had counseling and testing and
      8,027 (32.4%) met the high risk criteria. Median WT from physician visit to first
      screen was longer for women having genetic counseling only compared to those
      having counseling and testing (244 vs. 197 days). Women having counseling only
      also experienced the longest WT from physician visit to genetic counseling (88
      days; IQR = 10-174), which increased by year from 71 to 100 days (p < .0001).
      Among women having counseling and testing, WT from physician visit to counseling
      was shortest for mutation carriers (39 days; IQR = 4-100). Median WT from testing
      to laboratory report issue was 41 days (IQR = 22-70) and 17 days to disclosure of
      test results (IQR = 7-33). Both WTs decreased with year and were shorter for
      mutation carriers (33 days, IQR = 19-58; 15 days, IQR = 7-28, respectively).
      CONCLUSIONS: After implementation of the High Risk OBSP, women received timely
      genetic counseling, in particular those having counseling and testing. Effective
      triage models for physicians could reduce WT to GA after physician referral.

PMID- 29368426
TI  - Serum Endocan Levels are Associated With Paraoxonase 1 Concentration in Patients
      With Chronic Kidney Disease.
AB  - Endocan is a soluble proteoglycan released by the vascular endothelium. The
      increase of its serum levels is associated with inflammation, endothelial
      dysfunction and cardiovascular events in patients with chronic kidney disease
      (CKD). We studied the association of serum endocan with the lipid profile of 105
      CKD patients with dyslipidemia, divided in two groups, non-dialyzed (CKD, N = 57)
      and hemodialysis (HD, N = 48) in comparison with 30 normal controls (NC). We also
      analyzed endocan in relation with the concentration of two serum HDL-linked
      members of the paraoxonase (PON) family, PON1 and PON3, which have been
      previously found to have antiatherogenic properties. The results showed that
      endocan levels were significantly higher in HD patients than in CKD patients (P <
      0.001) and NC (P < 0.001). PON1 was significantly decreased only in HD patients
      compared to NC (P < 0.001), whereas PON3 was significantly increased in both
      patient groups (P < 0.001). Endocan levels were significantly and positively
      correlated with total cholesterol and LDL-C in CKD and additionally were
      negatively correlated with HDL-C in HD group. PON1 levels were significantly
      correlated with endocan in both groups, while no correlation was observed for
      PON3 in either group. Multiple regression analysis between endocan and the above
      lipid parameters in the total of patients revealed that endocan was independently
      associated only with PON1 (beta = -0.513, P = 0.002). It is concluded that the
      increase of serum endocan levels in patients with CKD may be associated with the
      decrease of PON1 concentration, irrespective of lipid alterations produced by
      atherosclerosis development.

PMID- 29368422
TI  - Clinical and Vitamin Response to a Short-Term Multi-Micronutrient Intervention in
      Brazilian Children and Teens: From Population Data to Interindividual Responses.
AB  - SCOPE: Micronutrients are in small amounts in foods, act in concert, and require
      variable amounts of time to see changes in health and risk for disease. These
      first principles are incorporated into an intervention study designed to develop
      new experimental strategies for setting target recommendations for food
      bioactives for populations and individuals. METHODS AND RESULTS: A 6-week
      multivitamin/mineral intervention is conducted in 9-13 year olds. Participants
      (136) are (i) their own control (n-of-1); (ii) monitored for compliance; (iii)
      measured for 36 circulating vitamin forms, 30 clinical, anthropometric, and food
      intake parameters at baseline, post intervention, and following a 6-week washout;
      and (iv) had their ancestry accounted for as modifier of vitamin baseline or
      response. The same intervention is repeated the following year (135
      participants). Most vitamins respond positively and many clinical parameters
      change in directions consistent with improved metabolic health to the
      intervention. Baseline levels of any metabolite predict its own response to the
      intervention. Elastic net penalized regression models are identified, and
      significantly predict response to intervention on the basis of multiple
      vitamin/clinical baseline measures. CONCLUSIONS: The study design, computational
      methods, and results are a step toward developing recommendations for optimizing
      vitamin levels and health parameters for individuals.

PMID- 29368427
TI  - Physical activity unveils the relationship between mitochondrial energetics,
      muscle quality, and physical function in older adults.
AB  - BACKGROUND: The concept of mitochondrial dysfunction in ageing muscle is highly
      controversial. In addition, emerging evidence suggests that reduced muscle
      oxidative capacity and efficiency underlie the aetiology of mobility loss in
      older adults. Here, we hypothesized that studying well-phenotyped older cohorts
      across a wide range of physical activity would unveil a range of mitochondrial
      function in skeletal muscle and in turn allow us to more clearly examine the
      impact of age per se on mitochondrial energetics. This also enabled us to more
      clearly define the relationships between mitochondrial energetics and muscle
      lipid content with clinically relevant assessments of muscle and physical
      function. METHODS: Thirty-nine volunteers were recruited to the following study
      groups: young active (YA, n = 2 women/8 men, age = 31.2 +/- 5.4 years), older
      active (OA, n = 2 women/8 men, age = 67.5 +/- 2.7 years), and older sedentary
      (OS, n = 8 women/11 men, age = 70.7 +/- 4.7 years). Participants completed a
      graded exercise test to determine fitness (VO2 peak), a submaximal exercise test
      to determine exercise efficiency, and daily physical activity was recorded using
      a tri-axial armband accelerometer. Mitochondrial energetics were determined by
      (i) 31 P magnetic resonance spectroscopy and (ii) respirometry of fibre bundles
      from vastus lateralis biopsies. Quadriceps function was assessed by isokinetic
      dynamometry and physical function by the short physical performance battery and
      stair climb test. RESULTS: Daily physical activity energy expenditure was
      significantly lower in OS, compared with YA and OA groups. Despite fitness being
      higher in YA compared with OA and OS, mitochondrial respiration, maximum
      mitochondrial capacity, Maximal ATP production/Oxygen consumption (P/O) ratio,
      and exercise efficiency were similar in YA and OA groups and were significantly
      lower in OS. P/O ratio was correlated with exercise efficiency. Time to complete
      the stair climb and repeated chair stand tests were significantly greater for OS.
      Interestingly, maximum mitochondrial capacity was related to muscle contractile
      performance and physical function. CONCLUSIONS: Older adults who maintain a high
      amount of physical activity have better mitochondrial capacity, similar to highly
      active younger adults, and this is related to their better muscle quality,
      exercise efficiency, and physical performance. This suggests that mitochondria
      could be an important therapeutic target for sedentary ageing associated
      conditions including sarcopenia, dynapenia, and loss of physical function.

PMID- 29368428
TI  - An analysis of effects of heterozygosity in dairy cattle for bovine tuberculosis
      resistance.
AB  - Genetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer
      a complementary control strategy. Hypothesising underlying non-additive genetic
      variation, we present an approach using genome-wide high density markers to
      identify genomic loci with dominance effects on bTB resistance and to test
      previously published regions with heterozygote advantage in bTB. Our data
      comprised 1151 Holstein-Friesian cows from Northern Ireland, confirmed bTB cases
      and controls, genotyped with the 700K Illumina BeadChip. Genome-wide markers were
      tested for associations between heterozygosity and bTB status using marker-based
      relationships. Results were tested for robustness against genetic structure, and
      the genotypic frequencies of a significant locus were tested for departures from
      Hardy-Weinberg equilibrium. Genomic regions identified in our study and in
      previous publications were tested for dominance effects. Genotypic effects were
      estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was
      significant at the chromosome-wide level, explaining 1.7% of the phenotypic
      variance. In the controls, there were fewer heterozygotes for rs43032684 (P <
      0.01) with the genotypic values suggesting that heterozygosity confers a
      heterozygote disadvantage. The region surrounding rs43032684 had a significant
      dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a
      parental gene involved in macrophage response to infection and within a copy
      number-variation region previously associated with nematode resistance. No
      dominance effect was found for the region on chromosome 11, as indicated by a
      previous candidate region bTB study. These findings require further validation
      with large-scale data.

PMID- 29368429
TI  - Accuracy of standardized 12-core template biopsies versus non-standardized
      biopsies for detection of Epstein Grade 5 prostate cancer regarding the histology
      of the prostatectomy specimen.
AB  - OBJECTIVE: To evaluate the effectiveness of EAU Guideline compliant transrectal
      ultrasound-guided 12-core prostate biopsies for detection of highly aggressive
      Epstein Grade 5 (Gleason Score 9-10) prostate cancer. METHODS: Two hundred ninety
      nine patients, treated by radical prostatectomy for prostate cancer, have been
      prospectively recorded in a database and were evaluated for this study. Pre
      operatively, all patients received transrectal ultrasound-guided biopsies
      according to inhomogeneous templates chosen by the referring urologist. We
      evaluated the outcomes according to a stratified group-analysis: Group 1 received
      less than 12 biopsies, Group 2 received more than 12 biopsies, and Group 3
      received exactly 12 biopsies, according to the EAU Guidelines template. After
      surgical removal of the prostate, 12 EAU Guideline-templated biopsies were
      performed in all prostatectomy specimens, directly after the surgery. Pre
      operative and post-operative Epstein Grade 5 biopsy detection rates were
      thereafter correlated with these prostatectomy specimens. RESULTS: In
      prostatectomy specimens, the histology of 12 patients (4.0%) were Epstein Grade
      1, 31 patients (10.5%) were Epstein Grade 2, 190 patients (63.5%) were Epstein
      Grade 3, 27 patients (9%) were Epstein Grade 4, and 39 patients (13%) were
      Epstein Grade 5. The detection rate of Epstein Grade 5 compared to the radical
      prostatectomy specimen was: Group 1: 23.0% pre-operatively and 61.5% post
      operatively, Group 2: 33.3% pre-operatively and 58.3% post-operatively; and Group
      3: 57.1% pre-operatively and 64.2% post-operatively. CONCLUSION: Detection rates
      of highly aggressive Epstein Grade 5 prostate cancer vary considerably according
      to the biopsy technique. EAU Guideline compliant 12-core template biopsies
      increase the detection rates of Epstein Grade 5 prostate cancer.

PMID- 29368430
TI  - Fetal heart size measurements as new predictors of homozygous alpha-thalassemia-1
      in mid-pregnancy.
AB  - OBJECTIVE: To evaluate the efficacy of using fetal heart size measurements
      derived from axial echocardiography to predict homozygous alpha-thalassemia-1.
      DESIGN: Prospective diagnostic study. SETTING: The carrier rate of alpha
      thalassemia-1 (-/alphaalpha) in China's Guangxi Zhuang Autonomous Region is
      approximately 15%. If both parents are carriers, the risk of homozygous alpha
      thalassemia-1 in one pregnancy is 25%. PATIENTS: Singleton mid-pregnancies at
      risk of homozygous alpha-thalassemia-1 were enrolled. OUTCOME MEASURES: Fetal
      heart measurements, including heart diameter (HD), heart length (HL), heart
      circumference (HC), and heart area (HA), were measured. The z-scores for these
      heart parameters were then calculated separately based on previously constructed
      z-score models. Finally, the accuracy of these predictive variables was analyzed
      and compared to that achieved by cardiothoracic ratio (CTR) using a receiver
      operating characteristic (ROC) curves analysis. RESULTS: A total of 214 singleton
      pregnancies were recruited. The discriminatory power of HA and HD z-scores was
      better (z-test P< .01) while that of HC and HL z-scores was comparable to (z-test
      P>.05) that of CTR. HD combined with HA z-scores had the highest sensitivity
      (100%), and the specificity of HD and/or HA z-scores was 100%. CONCLUSION: Fetal
      heart size measurements are novel, effective and noninvasive predictors of
      homozygosity for alpha-thalassemia-1 in mid-pregnancy. The discriminatory power
      of HD and HA z-scores was better than while that of HC and HL z-scores was
      comparable to that of CTR. Further investigation is needed to understand the
      effectiveness of these predictors.

PMID- 29368433
TI  - Non-invasive assessment of cellulitis from snapshot hyperspectral imaging - A
      primary study.

PMID- 29368431
TI  - Experience with genomic sequencing in pediatric patients with congenital cardiac
      defects in a large community hospital.
AB  - BACKGROUND: Congenital cardiac defects, whether isolated or as part of a larger
      syndrome, are the most common type of human birth defect occurring on average in
      about 1% of live births depending on the malformation. As there is an expanding
      understanding of the underlying molecular mechanisms by which a cardiac defect
      may occur, there is a need to assess the current rates of diagnosis of cardiac
      defects by molecular sequencing in a clinical setting. METHODS AND RESULTS: In
      this report, we evaluated 34 neonatal and pediatric patients born with a cardiac
      defect and their parents using exomized preexisting whole genome sequencing (WGS)
      data to model clinically available exon-based tests. Overall, we identified
      candidate variants in previously reported cardiac-related genes in 35% (12/34) of
      the probands. These include clearly pathogenic variants in two of 34 patients
      (6%) and variants of uncertain significance in relevant genes in 10 patients
      (26%), of these latter 10, 2 segregated with clinically apparent findings in the
      family trios. CONCLUSIONS: These findings suggest that with current knowledge of
      the proteins underlying CHD, genomic sequencing can identify the underlying
      genetic etiology in certain patients; however, this technology currently does not
      have a high enough yield to be of routine clinical use in the screening of
      pediatric congenital cardiac defects.

PMID- 29368432
TI  - Study of platelet-rich fibrin combined with rat periodontal ligament stem cells
      in periodontal tissue regeneration.
AB  - The objective of this study was to investigate the advantages and feasibility of
      periodontal tissue regeneration using platelet-rich fibrin (PRF) combined with
      rat periodontal ligament stem cells (PDLSCs) for the first time. We first
      determined the effect of PRF on rat PDLSCs in vitro. We next conducted an in vivo
      study, in which a tissue engineering technique was performed to repair
      periodontal defects in five groups: a blank group, collagen group (implanted
      collagen membrane), collagen + cells group (implanted collagen membrane and rat
      PDLSCs), PRF group (implanted PRF membrane) and PRF + cells group (implanted PRF
      membrane and rat PDLSCs). PRF greatly enhanced cell proliferation, mRNA and
      protein expression levels of bone sialoprotein (BSP), osteocalcin (OC), and runt
      related transcription factor 2 (RUNX2) and activity of alkaline phosphatase (ALP)
      in vitro. Transplantation of PRF combined with rat PDLSCs resulted in higher
      expression of osteopontin (Opn), collagen I (COL1A) and RUNX2 at both 12 and 24
      days after surgery. Micro-computed tomography and histological analysis showed
      substantially more new bone formation in the PRF + cells group at 24 days after
      surgery. Based on these results, we discuss the role of PRF in the proliferation
      and differentiation of rat PDLSCs and suggest that PRF combined with rat PDLSCs
      provides a valuable tool for periodontal tissue engineering.

PMID- 29368434
TI  - The Virtual Anemia Trial: An Assessment of Model-Based In Silico Clinical Trials
      of Anemia Treatment Algorithms in Patients With Hemodialysis.
AB  - In silico approaches have been proposed as a novel strategy to increase the
      repertoire of clinical trial designs. Realistic simulations of clinical trials
      can provide valuable information regarding safety and limitations of treatment
      protocols and have been shown to assist in the cost-effective planning of
      clinical studies. In this report, we present a blueprint for the stepwise
      integration of internal, external, and ecological validity considerations in
      virtual clinical trials (VCTs). We exemplify this approach in the context of a
      model-based in silico clinical trial aimed at anemia treatment in patients
      undergoing hemodialysis (HD). Hemoglobin levels and subsequent anemia treatment
      were simulated on a per patient level over the course of a year and compared to
      real-life clinical data of 79,426 patients undergoing HD. The novel strategies
      presented here, aimed to improve external and ecological validity of a VCT,
      significantly increased the predictive power of the discussed in silico trial.

PMID- 29368435
TI  - p62 as a therapeutic target for inhibition of autophagy in prostate cancer.
AB  - BACKGROUND: To test the hypothesis that p62 is an optimal target for autophagy
      inhibition and Verteporfin, a clinically available drug approved by FDA to treat
      macular degeneration that inhibits autophagy by targeting p62 protein, can be
      developed clinically to improve therapy for advanced prostate cancer. METHODS:
      Forced expression of p62 in PC-3 cells and normal prostate epithelial cells, RWPE
      1 and PZ-HPV7, were carried out by transfection of these cells with pcDNA3.1/p62
      or p62 shRNA plasmid. Autophagosomes and autophagic flux were measured by
      transfection of tandem fluorescence protein mCherry-GFP-LC3 construct. Apoptosis
      was measured by Annexin V/PI staining. Tumorigenesis was measured by a xenograft
      tumor growth model. RESULTS: Verteporfin inhibited cell growth and colony
      formation in PC-3 cells. Verteporfin generated crosslinked p62 oligomers,
      resulting in inhibition of autophagy and constitutive activation of Nrf2 as well
      as its target genes, Bcl-2 and TNF-alpha. In normal prostate epithelial cells,
      forced expression of p62 caused constitutive Nrf2 activation, development of
      apoptosis resistance, and Verteporfin treatment exhibited inhibitory effects.
      Verteporfin treatment also inhibited starvation-induced autophagic flux of these
      cells. Verteporfin inhibited tumorigenesis of both normal prostate epithelial
      cells with p62 expression and prostate cancer cells and decreased p62,
      constitutive Nrf2, and Bcl-xL in xenograft tumor tissues, indicating that p62 can
      be developed as a drug target against prostate cancer. CONCLUSIONS: p62 has a
      high potential to be developed as a therapeutic target. Verteporfin represents a
      prototypical agent with therapeutic potential against prostate cancer through
      inhibition of autophagy by a novel mechanism of p62 inhibition.

PMID- 29368436
TI  - Do women with complex alcohol and other drug use histories want women-only
      residential treatment?
AB  - BACKGROUND: Women-only addiction services tend to be provided on a poorly
      evidenced assumption that women want single-sex treatment. We draw upon women's
      expectations and experiences of women-only residential rehabilitation to
      stimulate debate on this issue. METHODS: Semi-structured interviews were
      undertaken with 19 women aged 25-44 years [currently in treatment (n = 9),
      successfully completed treatment (n = 5), left treatment prematurely (n = 5)].
      All had histories of physical or sexual abuse, and relapses linked to
      relationships with men. Interviews were audio-recorded, transcribed verbatim,
      coded and analysed inductively following Iterative Categorization. FINDINGS:
      Women reported routinely that they had been concerned, anxious or scared about
      entering women-only treatment. They attributed these feelings to previous poor
      relationships with women, being more accustomed to male company and negative
      experiences of other women-only residential settings. Few women said that they
      had wanted women-only treatment, although many became more positive after
      entering the women-only service. Once in treatment, women often explained that
      they felt safe, supported, relaxed, understood and able to open up and develop
      relationships with other female residents. However, they also described tensions,
      conflicts, mistrust and social distancing that undermined their treatment
      experiences. CONCLUSIONS: Women who have complex histories of alcohol and other
      drug use do not necessarily want or perceive benefit in women-only residential
      treatment.

PMID- 29368437
TI  - A Reconfigurable DNA Accordion Rack.
AB  - DNA nanostructure-based mechanical systems that control the distance between
      elements of interest have demonstrated great potential for various applications,
      including nanoplasmonic systems, molecular reactors, and other nanotechnology
      platforms. However, previously reported systems could not collectively manipulate
      a 2D or 3D nanoscale network of elements to various forms in multiple stages. A
      reconfigurable DNA accordion rack structure is introduced that is a DNA beam
      lattice that changes its conformation with a small amount of short-length DNA
      locks as the controlling input. The lattice shape of the 2D DNA accordion rack
      and the diameter and the height of the 3D DNA nanotubular structure made of the
      DNA accordion rack could be controlled. Furthermore, by sequentially repeating
      the detachment and the attachment of the different DNA locks using strand
      displacement, the shape reconfiguration was repeatedly carried out.

PMID- 29368438
TI  - Xom, a ventralizing factor, regulates beta-catenin levels and cell fate.

PMID- 29368439
TI  - In vivo skin reactions from pulsed-type, bipolar, alternating current
      radiofrequency treatment using invasive noninsulated electrodes.
AB  - BACKGROUND: Bipolar, alternating current radiofrequency (RF) conduction using
      invasive noninsulated electrodes consecutively generates independent tissue
      coagulation around each electrode and then, the converged coagulation columns.
      METHODS: Two pulsed-type RF models at the on-time pulse width/pulse pack of 30
      and 40 milliseconds were designed to amplify the early stage of RF-induced tissue
      reaction using hairless mouse skin in vivo. Then, structural and ultrastructural
      changes were evaluated in hairless mouse skin samples at baseline and immediately
      1 day, 3 days, 7 days, and 14 days after treatment. RESULTS: Immediately after
      pulsed-RF treatment, a few chrysanthemum-like zones of electrothermal coagulation
      and hypereosinophilic collagen fibers were found in the dermis and dermo
      subcutaneous fat junction. Histochemical staining for periodic acid-Schiff and
      immunohistochemical staining for type IV collagen revealed marked thickening of
      basement membranes. Transmission electron microscopy demonstrated that pulsed-RF
      treatment resulted in higher electron-dense and remarkably thicker lamina densa,
      as well as increases in anchoring fibrils, compared with untreated control
      specimens. Furthermore, CD31-positive blood vessels were smaller in size with a
      slit-like luminal appearance, without excessive damage to endothelial cells.
      CONCLUSION: Our data indicated that pulse-type, bipolar RF energy induces
      structural and ultrastructural changes in basement membranes and vascular
      components in hairless mouse skin.

PMID- 29368441
TI  - Advancing understanding and prediction in multiple stressor research through a
      mechanistic basis for null models.
AB  - Global environmental change is driven by multiple anthropogenic stressors.
      Conservation and restoration require understanding the individual and joint
      action of these stressors to evaluate and prioritize management measures. To
      date, most studies on multiple stressor effects have sought to identify potential
      stressor interactions, defined as deviations from null models, and related meta
      analyses have focused on quantifying the relative proportion of stressor
      interactions across studies. These studies have provided valuable insights about
      the complexity of multiple stressor effects, but remain largely devoid of a
      theoretical framework for null model selection and prediction of effects. We
      suggest that multiple stressor research would benefit by (1) integrating and
      developing additional null models and (2) selecting null models based on their
      mechanistic assumptions of the stressor mode of action and organism sensitivities
      as well as stressor-effect relationships for individuals and populations. We
      present a range of null models and outline their underlying assumptions and
      application in multiple stressor research. Moving beyond mere description
      requires multiple stressor research to shift its focus from identifying
      statistically significant interactions to the use and development of mechanistic
      (null) models. Justified selection of the appropriate null model is a first step
      to achieve this.

PMID- 29368442
TI  - Improved insulin sensitivity and secretion in prediabetic patients with adrenal
      insufficiency on dual-release hydrocortisone treatment: a 36-month retrospective
      analysis.
AB  - OBJECTIVE: Dual-release hydrocortisone (DR-HC) provides physiological cortisol
      exposure, leading to an improvement of anthropometric and metabolic parameters.
      The aim of the study was to evaluate the effects of DR-HC on insulin secretion
      and sensitivity and cardiometabolic risk, indirectly expressed by the visceral
      adiposity index (VAI). DESIGN AND PATIENTS: Retrospective analysis of 49
      patients, 13 with primary and 36 with secondary adrenal insufficiency (AI),
      respectively, on conventional glucocorticoid treatment at baseline and switched
      to DR-HC for 36 months. Overall, 24 patients had AI-pre-diabetes (impaired
      fasting glucose, impaired glucose tolerance and the combination), and 25 had AI
      normal glucose tolerance (NGT). MEASUREMENTS: Clinical and metabolic parameters,
      including VAI, insulin secretion and sensitivity indexes (fasting insulinaemia,
      AUC2 h insulinaemia , oral disposition index [Dio] and ISI-Matsuda), were
      evaluated. RESULTS: In patients with AI-NGT and AI-prediabetes, a significant
      decrease in BMI (P = .017 and P < .001), waist circumference (P = .008 and P <
      .001), HbA1c (P = .034 and P = .001) and a significant increase in HDL-C (P =
      .036 and P = .043) was, respectively, observed. In addition, in prediabetic
      patients, only we found a significant decrease in insulinaemia (P = .014), AUC2 h
      insulinaemia (P = .038) and VAI (P = .001), in concomitance with a significant
      increase in DIo (P = .041) and ISI-Matsuda (P = .038). CONCLUSIONS: Long-term DR
      HC therapy is associated with an improvement in insulin secretion and sensitivity
      in patients with prediabetes. However, all patients appear to benefit from the
      treatment in terms of improvement of metabolic and anthropometric parameters.
      Larger studies are required to confirm our preliminary data.

PMID- 29368440
TI  - Sexualized drug use ('chemsex') and high-risk sexual behaviours in HIV-positive
      men who have sex with men.
AB  - OBJECTIVES: The incidence of sexually transmitted infections (STIs) and HIV
      infection remains high in gay, bisexual, and other men who have sex with men
      (MSM) in the UK, and sexualized drug use ("chemsex") and injecting drug use
      ("slamsex") may play a part in this. We aimed to characterize HIV-positive MSM
      engaging in chemsex/slamsex and to assess the associations with self-reported STI
      diagnoses and sexual behaviours. METHODS: Data from a 2014 survey of people
      attending HIV clinics in England and Wales were linked to clinical data from
      national HIV surveillance records and weighted to be nationally representative.
      Multivariable logistic regression assessed the associations of chemsex and
      slamsex with self-reported unprotected anal intercourse (UAI), serodiscordant UAI
      (sdUAI) (i.e. UAI with an HIV-negative or unknown HIV status partner), sdUAI with
      a detectable viral load (>50 HIV-1 RNA copies/mL), hepatitis C, and bacterial
      STIs. RESULTS: In the previous year, 29.5% of 392 sexually active participants
      engaged in chemsex, and 10.1% in slamsex. Chemsex was significantly associated
      with increased odds of UAI [adjusted odds ratio (AOR) 5.73; P < 0.001], sdUAI
      (AOR 2.34; P < 0.05), sdUAI with a detectable viral load (AOR 3.86; P < 0.01),
      hepatitis C (AOR 6.58; P < 0.01), and bacterial STI diagnosis (AOR 2.65; P <
      0.01). Slamsex was associated with increased odds of UAI (AOR 6.11; P < 0.05),
      hepatitis C (AOR 9.39; P < 0.001), and bacterial STI diagnosis (AOR 6.11; P <
      0.001). CONCLUSIONS: Three in ten sexually active HIV-positive MSM engaged in
      chemsex in the past year, which was positively associated with self-reported
      depression/anxiety, smoking, nonsexual drug use, risky sexual behaviours, STIs,
      and hepatitis C. Chemsex may therefore play a role in the ongoing HIV and STI
      epidemics in the UK.

PMID- 29368443
TI  - Barbigerone reverses multidrug resistance in breast MCF-7/ADR cells.
AB  - Development of agents to overcome multidrug resistance (MDR) is one of the
      important strategies in cancer chemotherapy, and P-glycoprotein (P-gp) correlates
      with the degree of resistance. As a naturally occurring isoflavone, whether
      barbigerone (BA) could reverse MDR, is unknown. In this paper, we evaluated
      effects of BA on reversing P-gp mediated MDR of adriamycin (ADR)-resistant human
      breast carcinoma (MCF-7/ADR) cells. BA (0.5 MUM) treatment showed strong potency
      to increase ADR cytotoxicity toward MCF-7/ADR cells. It was also demonstrated
      that BA time- and dose-dependently increased accumulations of ADR and reduced the
      efflux in MCF-7/ADR cells, pretreatment of these cells with BA might relocalized
      ADR to the nuclei. Furthermore, the results also revealed that BA did not affect
      P-gp, but alter P-gp ATPase activity. Intravenous administration of BA
      significantly increased anticancer efficacy of ADR to MCF-7/ADR xenograft model
      in nude mice. These results revealed that BA might reverse P-gp mediated MDR
      through inhibition of ATPase activity, which indicated a novel use of BA as a
      potent candidate for cancer chemotherapy.

PMID- 29368444
TI  - Fabrication of an ionic-liquid-based polymer monolithic column and its
      application in the fractionation of proteins from complex biosamples.
AB  - An ionic-liquid-based polymer monolithic column was synthesized by free radical
      polymerization within the confines of a stainless-steel column (50 mm * 4.6 mm
      id). In the processes, ionic liquid and stearyl methacrylate were used as dual
      monomers, ethylene glycol dimethacrylate as the cross-linking agent, and
      polyethylene glycol 200 and isopropanol as co-porogens. Effects of the
      prepolymerization solution components on the properties of the resulting
      monoliths were studied in detail. Scanning electron microscopy, nitrogen
      adsorption-desorption measurements, and mercury intrusion porosimetry were used
      to investigate the morphology and pore size distribution of the prepared
      monoliths, which showed that the homemade ionic-liquid-based monolith column
      possessed a relatively uniform macropore structure with a total macropore
      specific surface area of 44.72 m2 /g. Compared to a non-ionic-liquid-based
      monolith prepared under the same conditions, the ionic-liquid-based monolith
      exhibited excellent selectivity and high performance for separating proteins from
      complex biosamples, such as egg white, snailase, bovine serum albumin digest
      solution, human plasma, etc., indicating promising applications in the
      fractionation and analysis of proteins from the complex biosamples in proteomics
      research.

PMID- 29368446
TI  - Optical coherence tomography image processing for in vivo 3-dimensional
      visualization of basal cell carcinoma.

PMID- 29368445
TI  - Lactobacillus reuteri strains protect epithelial barrier integrity of IPEC-J2
      monolayers from the detrimental effect of enterotoxigenic Escherichia coli.
AB  - Lactobacillus reuteri is an inhabitant of the gastrointestinal (GI) tract of
      mammals and birds and several strains of this species are known to be effective
      probiotics. The mechanisms by which L. reuteri confers its health-promoting
      effects are far from being fully understood, but protection of the mucosal
      barrier is thought to be important. Leaky gut is a state of abnormal intestinal
      permeability with implications for the pathophysiology of various
      gastrointestinal disorders. Enterotoxigenic Escherichia coli (ETEC) can invade
      the intestinal mucosa and induce changes in barrier function by producing
      enterotoxin or by direct invasion of the intestinal epithelium. Our hypothesis
      was that L. reuteri can protect the mucosal barrier, and the goal of the study
      was to challenge this hypothesis by monitoring the protective effect of L.
      reuteri strains on epithelial dysfunction caused by ETEC. Using an infection
      model based on the porcine intestinal cell line IPEC-J2, it was demonstrated that
      pretreatment of the cells with human-derived L. reuteri strains (ATCC PTA 6475,
      DSM 17938 and 1563F) and a rat strain (R2LC) reduced the detrimental effect of
      ETEC in a dose-dependent manner, as monitored by permeability of FITC-dextran and
      transepithelial electrical resistance (TEER). Moreover, the results revealed that
      ETEC upregulated proinflammatory cytokines IL-6 and TNFalpha and decreased
      expression of the shorter isoform of ZO-1 (187 kDa) and E-cadherin. In contrast,
      pretreatment with L. reuteri DSM 17938 and 1563F downregulated expression of IL-6
      and TNFalpha, and led to an increase in production of the longer isoform of ZO-1
      (195 kDa) and maintained E-cadherin expression. Interestingly, expression of ZO-1
      (187 kDa) was preserved only when the infected cells were pretreated with strain
      1563F. These findings demonstrate that L. reuteri strains exert a protective
      effect against ETEC-induced mucosal integrity disruption.

PMID- 29368447
TI  - Supramolecular Modulation of Structural Polymorphism in Pathogenic alpha
      Synuclein Fibrils Using Copper(II) Coordination.
AB  - Structural variation of alpha-synuclein (alphaSyn) fibrils has been linked to the
      diverse etiologies of synucleinopathies. However, little is known about what
      specific mechanism provides alphaSyn fibrils with pathologic features. Herein, we
      demonstrate Cu(II)-based supramolecular approach for unraveling the formation
      process of pathogenic alphaSyn fibrils and its application in a neurotoxic
      mechanism study. The conformation of alphaSyn monomer was strained by
      macrochelation with Cu(II), thereby disrupting the fibril elongation while
      promoting its nucleation. This non-canonical process formed shortened, beta-sheet
      enriched alphaSyn fibrils (<0.2 MUm) that were rapidly transmitted and
      accumulated to neuronal cells, causing neuronal cell death, in sharp contrast to
      typical alphaSyn fibrils (ca. 1 MUm). Our approach provided the supramolecular
      basis for the formation of pathogenic fibrils through physiological factors, such
      as brain Cu(II).

PMID- 29368448
TI  - Low carbohydrate diets may increase risk of neural tube defects.
AB  - BACKGROUND: Folic acid fortification significantly reduced the prevalence of
      neural tube defects (NTDs) in the United States. The popularity of "low carb"
      diets raises concern that women who intentionally avoid carbohydrates, thereby
      consuming fewer fortified foods, may not have adequate dietary intake of folic
      acid. METHODS: To assess the association between carbohydrate intake and NTDs, we
      analyzed data from the National Birth Defects Prevention Study from 1,740 mothers
      of infants, stillbirths, and terminations with anencephaly or spina bifida
      (cases), and 9,545 mothers of live born infants without a birth defect (controls)
      conceived between 1998 and 2011. Carbohydrate and folic acid intake before
      conception were estimated from food frequency questionnaire responses. Restricted
      carbohydrate intake was defined as <=5th percentile among controls. Odds ratios
      were estimated with logistic regression and adjusted for maternal race/ethnicity,
      education, alcohol use, folic acid supplement use, study center, and caloric
      intake. RESULTS: Mean dietary intake of folic acid among women with restricted
      carbohydrate intake was less than half that of other women (p < .01), and women
      with restricted carbohydrate intake were slightly more likely to have an infant
      with an NTD (AOR = 1.30, 95% CI: 1.02, 1.67). CONCLUSIONS: This is the first
      study to examine the association between carbohydrate intake and NTDs among
      pregnancies conceived postfortification. We found that women with restricted
      carbohydrate intake were 30% more likely to have an infant with anencephaly or
      spina bifida. However, more research is needed to understand the pathways by
      which restricted carbohydrate intake might increase the risk of NTDs.

PMID- 29368449
TI  - Geographical and experimental contexts modulate the effect of warming on top-down
      control: a meta-analysis.
AB  - Ecologists have extensively investigated the effect of warming on consumer
      resource interactions, with experiments revealing that warming can strengthen,
      weaken or have no net effect on top-down control of resources. These experiments
      have inspired a body of theoretical work to explain the variation in the effect
      of warming on top-down control. However, there has been no quantitative attempt
      to reconcile theory with outcomes from empirical studies. To address the gap
      between theory and experiment, we performed a meta-analysis to examine the
      combined effect of experimental warming and top-down control on resource biomass
      and determined potential sources of variation across experiments. We show that
      differences in experimental outcomes are related to systematic variation in the
      geographical distribution of studies. Specifically, warming strengthened top-down
      control when experiments were conducted in colder regions, but had the opposite
      effect in warmer regions. Furthermore, we found that differences in the
      thermoregulation strategy of the consumer and openness of experimental arenas to
      dispersal can contribute to some deviation from the overall geographical pattern.
      These results reconcile empirical findings and support the expectation of
      geographical variation in the response of consumer-resource interactions to
      warming.

PMID- 29368452
TI  - Aetiology of hepatocellular carcinoma in South America.

PMID- 29368450
TI  - Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and
      allergic inflammation.
AB  - Asthma and chronic obstructive pulmonary disease (COPD), chronic airway
      inflammatory diseases characterized by airflow limitation, have different
      etiologies and pathophysiologies. Asthma-COPD Overlap (ACO) has recently been
      used for patients with mixed asthma and COPD. The pathophysiological mechanisms
      of ACO have not been clearly understood due to the lack of an appropriate murine
      model. To investigate its pathophysiology, we examined a murine model by allergen
      challenge in surfactant protein-D (SP-D)-deficient mice that spontaneously
      developed pulmonary emphysema. SP-D-deficient mice were sensitized and challenged
      by ovalbumin (OVA). Lungs and bronchoalveolar lavage fluid (BALF) were collected
      for analysis, and static lung compliance and airway hyperresponsiveness (AHR)
      were measured 48 h after the last OVA challenge. In SP-D-deficient, naive, or OVA
      challenged mice, the mean linear intercept and static lung compliance were
      increased compared with wild-type (WT) mice. There was no significant difference
      in goblet cell hyperplasia and the gene expression of Mucin 5AC (MUC5AC) between
      SP-D-deficient and WT OVA-challenged mice. In SP-D-deficient OVA-challenged mice,
      airway hyperresponsiveness was significantly enhanced despite the lower
      eosinophil count and the concentration of interleukin (IL)-5 and IL-13 in BALF
      compared with WT OVA-challenged mice at 120 ventilations per minute. When mice
      were ventilated at a lower ventilation frequency of 100 ventilations per minute,
      elevated airway hyperresponsiveness in SP-D-deficient OVA-challenged mice was
      diminished. This model of emphysematous change with allergic airway inflammation
      raises the possibility that frequency-dependent airway hyperresponsiveness may be
      involved in the pathophysiology of ACO.

PMID- 29368451
TI  - Regulation of skeletal myotube formation and alignment by nanotopographically
      controlled cell-secreted extracellular matrix.
AB  - Skeletal muscle has a well-organized tissue structure comprised of aligned
      myofibers and an encasing extracellular matrix (ECM) sheath or lamina, within
      which reside satellite cells. We hypothesize that the organization of skeletal
      muscle tissues in culture can affect both the structure of the deposited ECM and
      the differentiation potential of developing myotubes. Furthermore, we posit that
      cellular and ECM cues can be a strong determinant of myoblast fusion and
      morphology in 3D tissue culture environments. To test these, we utilized a
      thermoresponsive nanofabricated substratum to engineer anisotropic sheets of
      myoblasts which could then be transferred and stacked into multilayered tissues.
      Within such engineered tissues, we found that myoblasts rapidly sense topography
      and deposit structurally organized ECM proteins. Furthermore, the initial tissue
      structure was found to exert significant control over myoblast fusion and
      eventual myotube organization. These results highlight the importance of ECM
      structure on myoblast fusion and organization, and provide insights into
      substrate-mediated control of myotube formation in the development of novel, more
      effective, engineered skeletal muscle tissues. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part A: 106A: 1543-1551, 2018.

PMID- 29368453
TI  - The role of HLA-G in parasitic diseases.
AB  - Little attention has been devoted to the role of HLA-G gene and molecule on
      parasitic disorders, and the available studies have focused on malaria, African
      and American trypanosomiasis, leishmaniosis, toxoplasmosis and echinococcosis.
      After reporting a brief description regarding the role of the cells of innate and
      adaptive immune system against parasites, we reviewed the major features of the
      HLA-G gene and molecule and the role of HLA-G on the major cells of immune
      system. Increased levels of soluble HLA-G (sHLA-G) have been observed in patients
      presenting toxoplasmosis and in the active phase of echinococcosis. In addition,
      increased sHLA-G has also been associated with increased susceptibility to
      malaria and increased susceptibility to develop human African trypanosomiasis
      (HAT). In contrast, decreased membrane-bound HLA-G has been reported in placenta
      of patients infected with Plasmodium falciparum and in heart and colon of
      patients presenting Chagas disease. The 3' untranslated region of the HLA-G gene
      has been the main focus of studies on malaria, HAT and Chagas disease, exhibiting
      distinct patterns of associations. Considering that HLA-G is an immune checkpoint
      molecule, inhibiting the activity of several cells of the immune system, the
      excessive neoexpression and the increased sHLA-G levels together with the
      decreased constitutive tissue expression of membrane-bound HLA-G may be
      detrimental to the host infected with parasite agents.

PMID- 29368454
TI  - Motion-Induced Changes in Emission as an Effective Strategy for the Ratiometric
      Probing of Human Serum Albumin and Trypsin in Biological Fluids.
AB  - Herein, we report the formation of a highly luminescent, pH-sensitive,
      thermoreversible nanoaggregate in pure aqueous medium through the self
      agglomeration of carbazole-based amphiphiles. The self-assembly process
      restricted the intramolecular motion of the molecules and induced a change in its
      emission signal from blue to cyan, owing to an aggregation-induced emission (AIE)
      effect. A similar type of ratiometric response was also observed in the presence
      of human serum albumin (HSA). However, in this case, the molecular motion of the
      flexible fluorescent probe was restricted by its embedded microenvironment, owing
      to a motion-induced change in emission (MICE) effect, not by aggregation.
      Moreover, the probe showed quite high selectivity for HSA over other serum
      albumin proteins. Our carbazole-based fluorescent probes are a unique example of
      the ratiometric sensing of HSA through the sole involvement of reversible
      noncovalent interactions. Considering the important of HSA in clinical diagnosis,
      a wide range of biological fluids, such as human urine, saliva, and plasma, were
      screened to analyze their HSA content. In addition, this system was also employed
      for the detection of trypsin at subnanomolar concentrations through the digestion
      of HSA.

PMID- 29368455
TI  - Effect of preoperative immunonutrition on postoperative short-term outcomes of
      patients with head and neck squamous cell carcinoma.
AB  - BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) often
      acquire an impaired nutritional status resulting in compromised outcomes.
      Perioperative immunonutrition may have a positive effect on outcomes after
      elective surgery. METHODS: Short-term outcomes before and after implementation of
      preoperative immunonutrition were retrospectively assessed. Regression models
      adjusted for outcome predictors were used to compare the length of stay (LOS) in
      the hospital, local infections, and general complications. RESULTS: Four hundred
      eleven patients were included (control group = 209 and the intervention group =
      202). With immunonutrition, hospital LOS was significantly lower (median 6 vs 8
      days; adjusted mean difference of -5.65 days; P < .001) and local infections were
      significantly reduced (7.4% vs 15.3%; adjusted odds ratio [OR] 0.30; P = .006).
      Subgroup analysis showed more pronounced effects in patients with previous
      radiotherapy and extensive surgery. CONCLUSION: Patients receiving preoperative
      immunonutrition had a shorter hospital LOS and a lower rate for wound infections
      and local complications. These effects remained robust after a multivariate
      adjustment.

PMID- 29368456
TI  - Rates of sustained virological response 12 weeks after the scheduled end of
      direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the
      National German HCV registry: does HIV coinfection impair the response to DAA
      combination therapy?
AB  - OBJECTIVES: The European Association for the Study of the Liver (EASL) treatment
      recommendations for hepatitis C no longer discriminate between HIV/hepatitis C
      virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from
      Spain are questioning these recommendations on the basis of the findings of
      higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim
      of our study was to compare HCV cure rates in monoinfected and coinfected
      patients from Germany. METHODS: Data acquired from the Deutsches Hepatitis C
      Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV
      coinfected patients were included in the study. Rates of sustained virological
      response 12 weeks after the scheduled end of therapy (SVR12) were collected in
      both subgroups and in cirrhotic and noncirrhotic patients. RESULTS: HIV/HCV
      coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P <
      0.001) and younger than HCV-monoinfected subjects (46.5 +/- 9 vs. 53.8 +/- 12.5
      years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/MUL in
      63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12
      rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of
      488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657
      (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected
      patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV
      coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P =
      0.864). A treatment duration of 8 weeks did not reduce the percentage of patients
      with SVR12 in either subgroup (93.7% in both groups). CONCLUSIONS: We found high
      SVR12 rates in monoinfected as well as coinfected individuals. No differences
      were detected between the two subgroups regardless of whether there was
      accompanying liver cirrhosis or a shortened treatment duration.

PMID- 29368457
TI  - Performance comparison of the MOXY and PortaMon near-infrared spectroscopy muscle
      oximeters at rest and during exercise.
AB  - The purpose of the study was to compare muscle oxygenation as measured by two
      portable, wireless near-infrared spectroscopy (NIRS) devices under resting and
      dynamic conditions. A recently developed low-cost NIRS device (MOXY) was compared
      against an established PortaMon system that makes use of the spatially resolved
      spectroscopy algorithm. The influence of increasing external pressure on tissue
      oxygen saturation index (TSI) indicated that both devices are stable between 2
      and 20 mmHg. However, above this pressure, MOXY reports declining TSI values.
      Analysis of adipose tissue thickness (ATT) and TSI shows a significant, nonlinear
      difference between devices at rest. The devices report similar TSI (%) values at
      a low ATT (<7  mm) (PortaMon minus MOXY difference is +1.1+/-2.8%) with the major
      subsequent change between the devices occurring between 7 and 10 mm; at ATT
      values >10  mm the difference remains constant (-14.7+/-2.8%). The most likely
      explanation for this difference is the small source-detector separation (2.5 cm)
      in the MOXY resulting in lower tissue penetration into muscle in subjects with
      higher ATT. Interday test-retest reliability of resting TSI was evaluated on five
      separate occasions, with the PortaMon reporting a lower coefficient of variation
      (1.8% to 2.5% versus 5.7% to 6.2%). In studies on male subjects with low ATT,
      decreases in the TSI were strongly correlated during isometric exercise, arterial
      occlusion, and incremental arm crank exercise. However, the MOXY reports a
      greater dynamic range, particularly during ischemia induced by isometric
      contraction or occlusion (Delta74.3% versus Delta43.7%; hyperemia MAX-occlusion
      MIN). This study shows that in this subject group both MOXY and PortaMon produce
      physiologically credible TSI measures during rest and exercise. However, the
      absolute values obtained during exercise are generally not comparable between
      devices unless corrected by physiological calibration following an arterial
      occlusion.

PMID- 29368458
TI  - Learnable despeckling framework for optical coherence tomography images.
AB  - Optical coherence tomography (OCT) is a prevalent, interferometric, high
      resolution imaging method with broad biomedical applications. Nonetheless, OCT
      images suffer from an artifact called speckle, which degrades the image quality.
      Digital filters offer an opportunity for image improvement in clinical OCT
      devices, where hardware modification to enhance images is expensive. To reduce
      speckle, a wide variety of digital filters have been proposed; selecting the most
      appropriate filter for an OCT image/image set is a challenging decision,
      especially in dermatology applications of OCT where a different variety of
      tissues are imaged. To tackle this challenge, we propose an expandable learnable
      despeckling framework, we call LDF. LDF decides which speckle reduction algorithm
      is most effective on a given image by learning a figure of merit (FOM) as a
      single quantitative image assessment measure. LDF is learnable, which means when
      implemented on an OCT machine, each given image/image set is retrained and its
      performance is improved. Also, LDF is expandable, meaning that any despeckling
      algorithm can easily be added to it. The architecture of LDF includes two main
      parts: (i) an autoencoder neural network and (ii) filter classifier. The
      autoencoder learns the FOM based on several quality assessment measures obtained
      from the OCT image including signal-to-noise ratio, contrast-to-noise ratio,
      equivalent number of looks, edge preservation index, and mean structural
      similarity index. Subsequently, the filter classifier identifies the most
      efficient filter from the following categories: (a) sliding window filters
      including median, mean, and symmetric nearest neighborhood, (b) adaptive
      statistical-based filters including Wiener, homomorphic Lee, and Kuwahara, and
      (c) edge preserved patch or pixel correlation-based filters including nonlocal
      mean, total variation, and block matching three-dimensional filtering.

PMID- 29368459
TI  - The Hermphrodite of Charing Cross.

PMID- 29368460
TI  - Galvanic Humans.

PMID- 29368461
TI  - The Subject as Instrument: Galvanic Experiments, Organic Apparatus and Problems
      of Calibration.

PMID- 29368462
TI  - Shocking Subjects: Human Experiments and the Material Culture of Medical
      Electricity in Eighteenth-Century England.

PMID- 29368463
TI  - Pneumatic Chemistry, Self-Experimentation and the Burden of Revolution.

PMID- 29368464
TI  - Food Fights: Human Experiments in Late Nineteenth-Century Nutrition Physiology.

PMID- 29368465
TI  - Experimenting with Radium Therapy: In the Laboratory & the Clinic.

PMID- 29368466
TI  - Anthropometry, Race, and Eugenic Research: "Measurements of Growing Negro
      Children" at the Tuskegee Institute, 1932-1944.

PMID- 29368467
TI  - Nazi Human Experiments: The Victims' Perspective and the Post-Second World War
      Discourse.

PMID- 29368468
TI  - A Eugenics Experiment: Sterilization, Hyperactivity and Degeneration.

PMID- 29368469
TI  - [Genomic architecture of human chromosomal diseases].
AB  - The genomic architecture predisposed to the emergence of DNA copy number
      variation causing a new class of human chromosomal diseases-reciprocal
      microdeletion and microduplication syndromes- is reviewed in the paper. The
      molecular mechanisms of such chromosomal abnormalities are described. The
      problems of the interpretation of their clinical significance and genotype
      phenotype correlations are discussed. The classification of phenotypes due to
      reciprocal chromosomal microdeletions and microduplications is shown. Published
      by 2015, reciprocal mutations associated with inherited and congenital human
      pathology and involving 58 chromosomal regions are summarized.

PMID- 29368470
TI  - [The role of ATP-dependent chromatin remodeling complexes in regulation of
      genetic processes].
AB  - Compaction of the genomic DNA into the chromatin structure reduces the
      accessibility of DNAbinding protein sites and complicates the realization of
      replication and transcription. In the cell, the negative effects of DNA
      condensation into chromatin are overcome by recruiting the complexes that change
      the chromatin structure and are involved in the regulation of transcription and
      replication. The chromatin remodeling process includes the alteration of
      nucleosome position and chromatin density and changes in the histone composition
      of the nucleosomes. ATP-dependent chromatin remodeling is performed by enzymes
      chromatin remodeling complexes. The united activity of these enzymes forms the
      dynamic properties of chromatin during different nuclear processes such as
      transcription, replication, DNA repair, homological recombination, and chromatin
      assembly. In this review, we summarize the currently available data on the
      structure of chromatin remodeling complexes of different families, the pathways
      of their recruitment to certain chromatin sites, and their functional activity.

PMID- 29368471
TI  - The scope, purpose, and reasoning behind Senate Bill 602.

PMID- 29368472
TI  - The State Innovation Model (SIM) Plan: A Practical Guide for Practitioners.

PMID- 29368473
TI  - Legal Aspects of Neonatal Abstinence Syndrome.

PMID- 29368474
TI  - Building Resilient Communities: Preparedness and Response for Health Care and
      Public Health Professionals.

PMID- 29368475
TI  - Nonopiate Methods for Treatment of Opiate Dependence.

PMID- 29368476
TI  - [Inverted meiosis and its place in the evolution of sexual reproduction
      pathways].
AB  - Inverted meiosis is observed in plants (Cyperaceae and Juncaceae) and insects
      (Coccoidea, Aphididae) with holocentric chromosomes, the centromeres of which
      occupy from 70 to 90% of the metaphase chromosome length. In the first meiotic
      division (meiosis I), chiasmata are formed and rodlike bivalents orient
      equationally, and in anaphase I, sister chromatids segregate to the poles; the
      diploid chromosome number is maintained. Non-sister chromatids of homologous
      chromosomes remain in contact during interkinesis and prophase II and segregate
      in anaphase II, forming haploid chromosome sets. The segregation of sister
      chromatids in meiosis I was demonstrated by example of three plant species that
      were heterozygous for chromosomal rearrangements. In these species, sister
      chromatids, marked with rearrangement, segregated in anaphase I. Using
      fluorescent antibodies, it was demonstrated that meiotic recombination enzymes
      Spo11 and Rad5l, typical of canonical meiosis, functioned at the meiotic prophase
      I of pollen mother cells of Luzula elegance and Rhynchospora pubera. Moreover,
      antibodies to synaptonemal complexes proteins ASY1 and ZYP1 were visualized as
      filamentous structures, pointing to probable formation of synaptonemal complexes.
      In L. elegance, chiasmata are formed by means of chromatin threads containing
      satellite DNA. According to the hypothesis of the author of this review,
      equational division of sister chromatids at meiosis I in the organisms with
      inverted meiosis can be explained by the absence of specific meiotic proteins
      (shugoshins). These proteins are able to protect cohesins of holocentric
      centromeres from hydrolysis by separases at meiosis I, as occurs in the organisms
      with monocentric chromosomes and canonical meiosis. The basic type of inverted
      meiosis was described in Coccoidea and Aphididae males. In their females, the
      variants of parthenogenesis were also observed. Until now, the methods of
      molecular cytogenetics were not applied for the analysis of inverted meiosis in
      Coccoidea and Aphididae. Evolutionary, inverted meiosis is thought to have
      appeared secondarily as an adaptation of the molecular mechanisms of canonical
      meiosis to chromosome holocentrism.

PMID- 29368477
TI  - Endobronchial Hamartoma Causing Postobstructive Pneumonia.
AB  - The current case highlights an uncommon cause of recurrent pneumonia. A 76 year
      old female presented to her primary care physician multiple times with recurrent
      left lower lobe pneumonia. After multiple chest radiographs continued to show no
      improvement despite antibiotics, a CT of the chest was performed and showed an
      intraluminal lesion in the left lower lobe bronchus. An endoscopic biopsy was
      performed and showed the lesionto be a hamartoma. The patient subsequently
      underwent resection of the lesion and her symptoms resolved.  This case
      illustrates the need for further diagnostic testing when recurrent pneumonia
      presents with the same lobar distribution.

PMID- 29368478
TI  - Persistent Distress after Water Contamination.
AB  - Background: A chemical spill contaminated the public water supply of Charleston,
      West Virginia in January 2014 for at least a week. Psychological distress is
      common after disasters. Methods: We surveyed the exposed population to assess
      psychological distress during and three months after the incident. We inquired
      about stressors that might predict distress, adequacy of communication from
      public officials, and use of the water supply and perceptions of its safety three
      months after the incident. Results: Twenty six percent of interviewees had
      persistent symptoms of distress. Female sex, negative household experiences
      during the episode (especially having someone sick), and poor perception of
      communication increased odds of persistent distress. Households of respondents
      without persistent distress were significantly more likely to report drinking tap
      water (RR=1.95) than those with persistent distress. Conclusions: Distress in
      Charleston area residents persisted and may have resulted in continuing mistrust
      of the water supply.

PMID- 29368479
TI  - [Genotoxic effects of pesticide fipronil in somatic and generative cells of
      mice].
AB  - The pronounced genotoxic effect of fipronil in all used doses (4.75, 9.50, 19.00,
      and 31.70 mg/kg) at a single exposure in the liver, lungs and spleen was
      ascertained by the Comet assay. Organ specificity of genotoxic effects of the
      pesticide was revealed. The liver was the most sensitive to fipronil. Fipronil at
      a dose of 9.50 mg/kg in a single and repeated exposure (within 10 days) induced
      aberrations in mouse bone marrow cells with the frequency exceeding the
      spontaneous mutation rate (p < 0.01 and p < 0.001, respectively). Fipronil also
      showed genotoxic activity in the germ cells of the experimental animals, causing
      abnormalities of the structure of synaptonemal complexes in the spermatocytes.

PMID- 29368480
TI  - Hip Pain in the Pre-Arthritic Patient: A Guide for the Primary Care Physician.
AB  - Adolescents and young adults (less than 30 years of age) with pre-arthritic hip
      pain constitute a diagnostic dilemma for the primary care physician. The most
      common underlying diagnoses range from benign muscle strains/joint sprains to
      stress reactions, insufficiency fractures, and tears involving the articular
      cartilage/labrum in the setting of femoroacetabular impingement, a hip shape
      abnormality that is present in up to 90% of this age group. Undetected or left
      untreated these seemingly innocuous disorders can result in significant loss of
      function and, in some cases, irreversible joint damage. Despite sharing common
      predisposing factors, many of the above diagnoses can be identified with a
      focused history and physical examination. Conservative management may be safely
      initiated without advanced imaging, reserving orthopaedic consultation for
      refractorycases or more serious diagnoses. The presented focused hip clinical
      examination has 98% sensitivity in localizing intra-articular hip pathologyand
      will be helpful to direct appropriate referrals. This article will serve as a
      guide for primary care physicians undertaking the difficult task of evaluating
      and treating a young patient with hip pain.

PMID- 29368481
TI  - [Determination of the composition and the allelic state of disease and pest
      resistance genes in potato parental lines using DNA markers].
AB  - The allelic dosage of disease and pest resistance genes was determined in 11
      prospective potato varieties and hybrids by means of detecting the corresponding
      PCR DNA markers in their progeny from crosses with specially selected testers. It
      was revealed that most (65%) resistance genes in the analyzed parental lines were
      present as a single dominant allele (simplex). Nevertheless, we were able to find
      some multiplex lines valuable for breeding. The Yanka variety and the clone 52-03
      16 had one triplex and one duplex of resistance genes, the Lilea and Charaunik
      varieties and the clone 106-04-17 had two resistance genes in duplex, and the
      Uladar and Falvarak varieties and the clone 45-04-24 were duplex for some single
      genes. The highest number of multiplex lines was detected for the genes Ry sto ,
      H1, and Sen1. Only simplex genotypes were revealed for the Gro-1-4 and PLRV1
      genes.

PMID- 29368482
TI  - [Species divergence in Iris series Lacteae (Iridaceae) in Russia and adjacent
      countries based on chloroplast DNA sequence data].
AB  - In Russia, the species of the genus Iris L., series Lacteae Doronkin, the
      taxonomic structure of which still remains controversial, are found in the south
      of Siberia and the Russian Far East, as well as in other regions of Asia.
      Sequence analysis of three chloroplast DNA regions (rps4, trnL-trnF, and trnS
      trnG) shows that, in Russia and adjacent countries, there are two genetically and
      geographically isolated Lacteae species. I. oxypetala Bunge grows in the south of
      the Russian Far East, and I. lactea Pall. grows in Siberia, Mongolia, and
      Kazakhstan. Genetic differentiation between the populations of I. lactea is
      extremely low and statistically insignificant (the fixation index PhiST = 0.057,
      P > 0.05), pointing to the unity of the gene pool and the absence of other
      Lacteae species in this area.

PMID- 29368483
TI  - Using Capsule Endoscopy at an Academic Teaching Hospital in West Virginia: A
      Descriptive Analysis of our 7 year Experience and Determination of Diagnostic
      Yield for Obscure Gastrointestinal Bleeding.
AB  - Background: The aim of our study was to describe, analyze, and evaluate results
      of wireless capsule endoscopy (CE) as an imaging modality for various
      indications. Methods: We conducted a retrospective chart review study of all CE
      studies performed between January 1, 2007 and June 30, 2014 at Marshall
      University. The study included 272 patients between the ages of 21-85 years old.
      Results: The most common finding in our study was a normal study (57.7%) followed
      by small bowel erosions (14.3%),neoplasms (11.4%), Arteriovenous malformations
      (10.7%), inflammatory bowel disease (2.6%), and nonspecific findings (3.3%).
      Discussion: 90/209 patients who had indications for IDA, melena, or heme-positive
      stools demonstrated positive findings by CE; our diagnostic yield for obscure GI
      bleeding was therefore 43.1%.

PMID- 29368484
TI  - [Microsatellite markers polymorphism in the breeding nutria (Myocastor coypus)
      population in Poland].
AB  - The aim of the research was to establish a microsatellite panel to determine the
      genetic diversity within the breeding nutria population in Poland. In the study,
      92 animals representing six color forms were used. Ten fluorescently labeled
      microsatellite markers were investigated by multicolored capillary
      electrophoresis. All the microsatellites were polymorphic. The average
      heterozygosity observed among the population was 41%. The mean number of alleles
      per locus was 9.2. The average heterozygosity observed in the whole population
      was lower than expected. This implies that the nutria population deviates from
      the Hardy-Weinberg equilibrium. Low M values (from 0.078 to 0.545) of the Garza
      Williamson index reveal a reduction of genetic variation in the investigated
      population and suggest that the breeding nutria population is remnant.

PMID- 29368485
TI  - Subclavian Vein Central Line Catheter Mistakenly Placed in the Aorta: A Case
      Report and How to Avoid Complications.
AB  - An 85-year-old female with multiple medical problems presented with a sigmoid
      volvulus. While in the ICU, the patient required a central line because of poor
      peripheral access. The central line was mistakenly placed in the aorta while
      attempting to use the subclavian approach. In this manuscript we discussed ways
      of reducing complications and successfully placing subclavian vein catheters.

PMID- 29368486
TI  - [The haplomatch program for comparing Y-chromosome STR-haplotypes and its
      application to the analysis of the origin of Don Cossacks].
AB  - STR haplotypes of the Y chromosome are widely used as effective genetic markers
      in studies of human populations and in forensic DNA analysis. The task often
      arises to compare the spectrum of haplotypes in individuals or entire
      populations. Performing this task manually is too laborious and thus unrealistic.
      We propose an algorithm for counting similarity between STR haplotypes. This
      algorithm is suitable for massive analyses of samples. It is implemented in the
      computer program Haplomatch, which makes it possible to find haplotypes that
      differ from the target haplotype by 0, 1, 2, 3, or more mutational steps. The
      program may operate in two modes: comparison of individuals and comparison of
      populations. Flexibility of the program (the possibility of using any external
      database), its usability (MS Excel spreadsheets are used), and the capability of
      being applied to other chromosomes and other species could make this software a
      new useful tool in population genetics and forensic and genealogical studies. The
      Haplomatch software is freely available on our website www.genofond.ru. The
      program is applied to studying the gene pool of Cossacks. Experimental analysis
      of Y-chromosomal diversity in a representative set (N = 131) of Upper Don
      Cossacks is performed. Analysis of the STR haplotypes detects genetic proximity
      of Cossacks to East Slavic populations (in particular, to Southern and Central
      Russians, as well as to Ukrainians), which confirms the hypothesis of the origin
      of the Cossacks mainly due to immigration from Russia and Ukraine. Also, a small
      genetic influence of Turkicspeaking Nogais is found, probably caused by their
      occurrence in the Don Voisko as part of the Tatar layer. No similarities between
      haplotype spectra of Cossacks and Caucasus populations are found. This case study
      demonstrates the effectiveness of the Haplomatch software in analyzing large sets
      of STR haplotypes.

PMID- 29368487
TI  - [Analysis of the ITS1/ITS2 nuclear spacers and the secondary structure of 5.8S
      rRNA gene in endemic species Bellevalia sarmatica (Pall. ex Georgi) Woronow and
      related species of the subfamily scilloideae].
AB  - Sequence variability of the ITS spacers and 5.8S rRNA gene was examined in 11
      accessions of the subfamily Scilloideae, including seven accessions of rare and
      endangered species Bellevalia sarmatica from Volgograd region. The intraspecific
      polymorphism level of the examined ITS1-5.8S-ITS2 sequence of B. sarmatica
      accessions constituted 1.3%. The phylogenetic position of B. sarmatica within the
      genus Bellevalia was determined. It was demonstrated that B. sarmatica belonged
      to the section Nutantes, and the most closely related species were B. webbiana
      and B. dubia. Nucleotide substitutions in the 5.8S rRNA gene sequence of the
      analyzed Scilloideae accessions were identified and studied. The predicted
      secondary structure of 5.8S rRNA gene was constructed. It was demonstrated that
      in the examined accessions, mutations in the 5.8S rRNA gene were mainly localized
      in the third hairpin region and had no effect on the secondary structure of the
      5.8S rRNA molecule.

PMID- 29368488
TI  - [Identification and polymorphism of pectinase genes PGU in the Saccharomyces
      bayanus complex].
AB  - Pectinase (endo-polygalacturonase) is the key enzyme splitting plant pectin. The
      corresponding single gene PGU1 is documented for the yeast S. cerevisiae. On the
      basis of phylogenetic analysis of the PGU nucleotide sequence available in the
      GenBank, a family of divergent PGU genes is found in the species complex S.
      bayanus: S. bayanus var. uvarum, S. eubayanus, and hybrid taxon S. pastorianus.
      The PGU genes have different chromosome localization.

PMID- 29368491
TI  - [Gene therapy of arthritis].
AB  - Gene therapy can offer a new approach to arthritis treatment which acts at an
      inflammation site. Numerous studies show high efficacy of gene therapy in
      different models of arthritis in humans. Even a single injection of a recombinant
      vector results in a stable prolonged expression of a therapeutic gene and a
      longterm therapeutic effect. In contrast to biologic therapy involving numerous
      systemic injections of recombinant anti-inflammatory proteins, gene therapy does
      not produce systemic side effects. Vectors based on retroviruses, adenoviruses,
      adeno-associated viruses, and recombinant plasmids could provide delivery of
      target genes. Of significant importance is the development of noninvasive methods
      of gene therapy: intranasal and peroral. The current state of research in
      arthritis gene therapy is discussed in this review.

PMID- 29368490
TI  - Catechol-oxide-methyltransferase (COMT rs4680:G>A) gene polymorphism does not
      affect analgesics' demand after elective hip replaceme.
AB  - Pain in patients with hip osteoarthritis appears long before surgery, and
      requires effective management as it affects patient comfort and daily activities.
      Therefore, the search for factors influencing response rate to analgesics is
      mandatory. In recent years, increasing attention has been paid to genetic factors
      underlying pain threshold and treatment efficacy. Polymorphic gene of catechol
      oxide-methyltransferase (COMT) is a candidate gene associated with pain pathology
      and treatment response. The aim of the study was to evaluate association between
      the COMT rs4680:G>A polymorphism and demand for analgesics in patients subjected
      to elective hip replacement. The study included 196 patients after hip
      replacement surgery. Opioid demand was recorded and analgesic efficacy was scored
      using a four-level verbal pain intensity scale. COMT rs4680:G>A polymorphism was
      analysed by PCR-RFLP method. The studied COMT genotypes did not influence opioid
      administration in the studied patients from the day of surgery till day 6
      afterwards. The distribution of the COMT rs4680:G>A in the studied subjects was
      as follows: GA-52.04%, AA-23.98% and GG-23.98%. It can be concluded that the COMT
      rs4680:G>A polymorphism is not associated with opioid demand in patients after
      elective hip replacement.

PMID- 29368489
TI  - Tobacco-use Cessation Counseling Service Usage.
AB  - Objectives: Tobacco-use is common among elderly lung cancer patients and
      continued tobacco-use can impact prognosis. This study evaluates patterns of
      receipt of Tobacco-use Cessation Counseling (TCC) services among these patients.
      Methods: Using West Virginia Cancer Registry-Medicare linked database (2004
      2007), we identified elderly patients with lung cancer (n = 922) and categorized
      them by receipt of TCC services. Hierarchical generalized logistic model was
      constructed and survival outcomes were analyzed by Kaplan-Meier analysis, Log
      Rank test, and Cox proportional hazards modeling. Results: Majority of patients
      (76.7%) received TCC services. Unadjusted analysis showed favorable survival
      outcomes in patients who received TCC services. However, adjusted lung cancer
      mortality risk was no different between the groups (HR (95% CI) = 1.78 (0.87
      3.64)). Conclusion: This study highlights the critical need to address
      disparities in receipt of TCC services among elderly. Although lung cancer
      preventive services are covered under the Medicare program, underutilization of
      these services is a concern.

PMID- 29368492
TI  - [Hybridological analysis of inheritance of mosaic nptII gene expression in
      transgenic tobacco plants].
AB  - On the basis of the results of hybridological analysis, it was established that
      significant differences in the stability of manifestation of the nptII gene
      expression are observed between the Nu5 and Nu6 lines obtained from the same
      initial Nu21 transformant (in spite of the identical genetic environment).
      Relatively stable expression of the marker gene is registered in the Nu5 line;
      the frequencies of detection of mosaic descendants are not high. The Nu6 line is
      characterized by a high frequency of the appearance of mosaic plants (up to
      100%), indicating an increase in the marker gene inactivation in this line. When
      combining the nptII gene alleles in the hybrid genome, the allele coming from the
      Nu6 line was manifested as semidominant and had a suppressing effect on the
      allele coming from the Nu5 line. No transinactivation phenomena at the level of
      phenotype were detected during the interaction of the nptII gene alleles from the
      Nu5 and Nu6 lines in diheterozygote with the alleles of homologous genes
      inactivated at the transcriptional or post-transcriptional levels. During
      segregation to F2, separation of the Nu21 line progeny into two independent
      groups with preservation of the different character of the marker gene expression
      (with a moderate level of appearance of mosaic plants for the Nu5 line and with
      high level for the Nu6 line) was again registered. Further studies are directed
      to detection of the mechanisms leading to the mosaic type of the studied gene
      manifestation in transgenic plants of the Nu5 and Nu6 lines.

PMID- 29368493
TI  - [Current state of the genetic polymorphism in spring barley (Hordeum vulgare L.)
      from Russia assessed by the alleles of hordein-coding loci].
AB  - Starch gel electrophoresis was performed to study the polymorphism of hordeins
      encoded by the Hrd A, Hrd B, and Hrd F loci in 211 varieties of spring barley.
      For 41 of these varieties, the genetic formulas were established for the first
      time. In the two samples of varieties, the comparative analysis of allelic
      diversity and allele frequencies of hordein-coding loci was carried out. The
      first sample consisted of 101 spring barley varieties approved for the use on the
      territory of the Russian Federation in 1999, while the second sample included 160
      spring barley varieties that were approved in 2014; 49 of these varieties were
      common for both samples. It is demonstrated that the current tendency to
      reduction of the proportion of heterogeneous spring barley varieties is mainly
      due to the introduction of foreign varieties homogeneous for the hordein-coding
      loci. At the same time, there is an increase in polymorphism of hordein-coding
      loci in modern spring barley varieties. The number of alleles for the Hrd A locus
      increased by five alleles, and for the Hrd B locus, by nine alleles. Along with
      the alleles recorded earlier in barley landrace populations and varieties bred in
      20th century, three novel alleles of the Hrd A locus and four alleles of the Hrd
      B locus were identified. The number of alleles of the Hrd F locus remained
      unchanged (four), and the changes in their frequencies were small. At the same
      time, the changes in frequency observed for some alleles of the Hrd A and Hrd B
      loci were statistically significant. All newly identified alleles of hordein
      coding loci were found with low frequencies (from 0.003 to 0.006), so despite the
      increased number of alleles, no statistically significant increase in genetic
      diversity in terms of MU and PIC indices was observed.

PMID- 29368494
TI  - [Spatial and temporal variations of the chromosomal inversion frequencies across
      the range of malaria mosquito Anopheles messeae Fall. (Culicidae) during the 40
      year monitoring period].
AB  - The analysis of personal and published data on the frequency dynamics of
      chromosomal inversions within the range of Anopheles messeae obtained during the
      period from 1974 through 2014 is presented. The results showed that, in general,
      across the species range, during the 40 years of genetic monitoring, there was a
      steady (stationary) clinal distribution of inversions in the first decade (1974
      1985). Then, over the period of five years (1986-1990), there was a considerable
      change in the inversion frequencies in favor of southwestern chromosomal variants
      (particularly strongly fixed in the Tomsk population), and from 1992 to the
      present time, these changes remained and were relatively stably reproduced in
      most parts of the range. It was noted that the jump in warming during the winter
      of 1981-1982 led to a correlated jump of the southwestern chromosomes in the
      Tomsk population. In connection with the general tendency toward the increase in
      average winter temperatures, a sharp decrease in the 2R1 chromosome frequency in
      the Siberian region and Syktyvkar in the period from 1992 to the present time was
      observed. There is reason to assume that, over the past decade, the northern
      boundary of the An. messeae range moved northward to the tundra zone.

PMID- 29368495
TI  - Rationally addressing the opiate drug problem.

PMID- 29368496
TI  - [Genetic polymorphism, haplotype distribution, and phylogeny of Daphnia
      (Cladocera: Anomopoda) species from the water bodies of russia as inferred from
      the 16S mtDNA gene sequencing].
AB  - The data on the genetic polymorphism of the most widespread Daphnia species
      occupying different water bodies of Russia are presented. The phylogenetic
      relationships between the examined species were established, and the haplotype
      networks were constructed. A fragment of the 16S mitochondrial DNA gene was used
      as a genetic marker. The results of molecular phylogenetic analysis generally
      coincided with modern concepts in the systematics of the genus Daphnia. The
      representatives of the divergent mitochondrial lineages within the D. longispina,
      D. pulex, and D. magna complex remain poorly investigated morphologically. For D.
      dentifera, a new habitat on the territory of Russia, namely, the water bodies of
      the Lake Baikal basin, was identified. A conclusion was made that the 16S mtDNA
      gene could be successfully used in phylogeographic analysis of the genus Daphnia.

PMID- 29368497
TI  - Choosing Wisely.

PMID- 29368498
TI  - [Chromosomal polymorphism in the populations of malaria mosquito Anopheles
      messeae (Diptera, Culicidae) in the Volga region].
AB  - We studied the species composition and chromosomal variability of malaria
      mosquitoes in the Volga Basin (Upper, Middle, and Lower Volga regions). We
      investigated larvae karyotypes of sibling species of the Anopheles maculipennis
      group. We calculated the frequencies of chromosomal inversions in the local
      populations of the dominant species An. messeae. We discovered that karyotypic
      structure of An. messeae populations depends on landscape-climatic zones.
      Populations of the Upper, Middle and Lower Volga differ in frequency of
      chromosome inversions XL, 2R, 3R, and 3L.

PMID- 29368499
TI  - [1,2,4]Triazolo[1,5-a]pyridine as Building Blocks for Universal Host Materials
      for High-Performance Red, Green, Blue and White Phosphorescent Organic Light
      Emitting Devices.
AB  - The electron-accepting [1,2,4]triazolo[1,5-a]pyridine (TP) moiety was introduced
      to build bipolar host materials for the first time, and two host materials based
      on this TP acceptor and carbazole donor, namely, 9,9'-(2-([1,2,4]triazolo[1,5
      a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (o-CzTP) and 9,9'-(5
      ([1,2,4]triazolo[1,5-a]pyridin-2-yl)-1,3-phenylene)bis(9H-carbazole) (m-CzTP),
      were designed and synthesized. These two TP-based host materials possess a high
      triplet energy (>2.9 eV) and appropriate highest occupied molecular
      orbital/lowest unoccupied molecular orbital levels as well as the bipolar
      transporting feature, which permits their applicability as universal host
      materials in multicolor phosphorescent organic light-emitting devices (PhOLEDs).
      Blue, green, and red PhOLEDs based on o-CzTP and m-CzTP with the same device
      configuration all show high efficiencies and low efficiency roll-off. The devices
      hosted by o-CzTP exhibit maximum external quantum efficiencies (etaext) of 27.1,
      25.0, and 15.8% for blue, green, and red light emitting, respectively, which are
      comparable with the best electroluminescene performance reported for FIrpic-based
      blue, Ir(ppy)3-based green, and Ir(pq)2(acac)-based red PhOLEDs equipped with a
      single-component host. The white PhOLEDs based on the o-CzTP host and three
      lumophors containing red, green, and blue emitting layers were fabricated with
      the same device structure, which exhibit a maximum current efficiency and etac of
      40.4 cd/A and 17.8%, respectively, with the color rendering index value of 75.

PMID- 29368500
TI  - Formaldehyde Detoxification Creates a New Wheel for the Folate-Driven One-Carbon
      "Bi"-cycle.

PMID- 29368501
TI  - Colloidal Quantum Dot Inks for Single-Step-Fabricated Field-Effect Transistors:
      The Importance of Postdeposition Ligand Removal.
AB  - Colloidal quantum dots are a class of solution-processed semiconductors with good
      prospects for photovoltaic and optoelectronic applications. Removal of the
      surfactant, so-called ligand exchange, is a crucial step in making the solid
      films conductive, but performing it in solid state introduces surface defects and
      cracks in the films. Hence, the formation of thick, device-grade films have only
      been possible through layer-by-layer processing, limiting the technological
      interest for quantum dot solids. Solution-phase ligand exchange before the
      deposition allows for the direct deposition of thick, homogeneous films suitable
      for device applications. In this work, fabrication of field-effect transistors in
      a single step is reported using blade-coating, an upscalable, industrially
      relevant technique. Most importantly, a postdeposition washing step results in
      device properties comparable to the best layer-by-layer processed devices,
      opening the way for large-scale fabrication and further interest from the
      research community.

PMID- 29368502
TI  - Nondestructive Readout Complementary Resistive Switches Based on Ferroelectric
      Tunnel Junctions.
AB  - Recently, complementary resistive switches (CRSs) have attracted considerable
      attention because of the effective suppression of the sneak leakage that is an
      inherent problem of crossbar memory arrays. In this work, we propose a new CRS
      device enabling nondestructive readout based on back-to-back in-series
      Pt/BaTiO3/Nb:SrTiO3 ferroelectric tunnel junctions (FTJs). The FTJ elements
      exhibit not only a nonvolatile resistance switching but also a typical diode-like
      transport in the high-resistance state (HRS) because of the ferroelectric
      enhancement on the Schottky barrier of the BaTiO3/Nb:SrTiO3 interface. With the
      rectifying characteristic, the complementary HRS + LRS (low-resistance state) and
      LRS + HRS states can be well-distinguished and nondestructively read out by a
      subthreshold voltage. In addition, the sneak current is significantly suppressed
      in the Pt/BaTiO3/Nb:SrTiO3 CRS crossbar array, and the maximum scaling size is
      increased by about 50 times, in comparison to the array constituted by only the
      single-FTJ devices. These results facilitate the design of high-performance
      resistive memories based on the crossbar architecture.

PMID- 29368503
TI  - Water on Graphene-Coated TiO2: Role of Atomic Vacancies.
AB  - Beyond two-dimensional (2D) materials, interfaces between 2D materials and
      underlying supports or 2D-coated metal or metal oxide nanoparticles exhibit
      excellent properties and promising applications. The hybrid interface between
      graphene and anatase TiO2 shows great importance in photocatalytic, catalytic,
      and nanomedical applications due to the excellent and complementary properties of
      the two materials. Water, as a ubiquitous and essential element in practical
      conditions and in the human body, plays a significant role in the applications of
      graphene/TiO2 composites for both electronic devices and nanomedicine. Carbon
      vacancies, as common defects in chemically prepared graphene, also need to be
      considered for the application of graphene-based materials. Therefore, the
      behavior of water on top and at the interface of defective graphene on anatase
      TiO2 surface was systematically investigated by dispersion-corrected hybrid
      density functional calculations. The presence of the substrate only slightly
      enhances the on-top adsorption and reduces the on-top dissociation of water on
      defective graphene. However, at the interface, dissociated water is largely
      preferred compared with undissociated water on bare TiO2 surface, showing a
      prominent cover effect. Reduced TiO2 may further induce oxygen diffusion into the
      bulk. Our results are helpful to understand how the presence of water in the
      surrounding environment affects structural and electronic properties of the
      graphene/TiO2 interface and thus its application in photocatalysis, electronic
      devices, and nanomedicine.

PMID- 29368504
TI  - Single-Crystal BiFeO3 Nanoplates with Robust Antiferromagnetism.
AB  - Freestanding and single-crystal BiFeO3 (BFO) nanoplates have been successfully
      synthesized by a fluoride ion-assisted hydrothermal method, and the thickness of
      the nanoplates can be effectively tailored from 80 to 380 nm by the concentration
      of fluoride ions. It is revealed that BFO nanoplates grew via an oriented
      attachment of layer by layer, giving rise to the formation of the inner interface
      within the nanoplates. In particular, antiferromagnetic (AFM) phase-transition
      temperature (Neel temperature, TN) of the BFO nanoplates is significantly
      enhanced from typical 370 to ~512  degrees C, whereas the Curie temperature (TC)
      of the BFO nanoplates is determined to be ~830  degrees C, in good agreement with
      a bulk value. The combination of scanning transmission electron microscopy,
      electron energy loss spectroscopy, and the first-principle calculations reveals
      that the interfacial tensile strain remarkably improves the stability of AFM
      ordering, accounting for the significant enhancement in TN of BFO plates.
      Correspondingly, the tensile strain induced the polarization and oxygen
      octahedral tilting has been observed near the interface. The findings presented
      here suggest that single-crystal BFO nanoplate is an ideal system for exploring
      an intrinsic magnetoelectric property, where a tensile strain can be a very
      promising approach to tailor AFM ordering and polarization rotation for an
      enhanced coupling effect.

PMID- 29368505
TI  - CoHPi Nanoflakes for Enhanced Oxygen Evolution Reaction.
AB  - Electrochemical splitting of water to produce hydrogen and oxygen is an important
      process for many energy storage and conversion devices. Developing efficient,
      robust, low-cost, and earth-abundant electrocatalysts for the oxygen evolution
      reaction (OER) is therefore of great importance. Herein, we report a novel method
      to prepare two-dimensional cobalt hydrogen phosphate (CoHPi) through chemical
      conversion of alpha-Co(OH)2 precursor at room temperature. The CoHPi nanoflakes
      with the thickness of 3 nm contain HPO42- anions, which have been demonstrated to
      serve as a proton acceptor in proton-coupled electron-transfer (PCET) process of
      OER. Due to their ultrathin structure and the PCET merit of anions, the CoHPi
      nanoflakes show enhanced OER activity as well as excellent stability in prolonged
      OER operation. Through further mechanism study, the observed performances can be
      ascribed to enriched active sites, surface superhydrophilicity, and rapid
      electron/proton and mass transfers.

PMID- 29368506
TI  - Panitumumab-Conjugated and Platinum-Cored pH-Sensitive Apoferritin Nanocages for
      Colorectal Cancer-Targeted Therapy.
AB  - Apoferritin (AF) is a natural nontoxic iron carrier and has a natural hollow
      structure that can be used to deliver small molecules. The surface of AF has many
      amine functional groups that can be modified to create targeted ligands. We
      loaded oxaliplatin onto AF, which was then used as a template to conjugate with
      panitumumab via a polyethylene glycol linker. The oxaliplatin-loaded AF
      conjugated with panitumumab (AFPO) was designed to specifically target cell lines
      expressing epidermal growth factor receptor (EGFR). AFPO efficiently released
      oxaliplatin and suppressed tumor cell growth. Furthermore, the novel AFPO
      nanocages showed significant inhibition and greater accumulation in tumor models
      with high EGFR expression in vivo. Our study revealed that combining panitumumab
      and oxaliplatin into one formulation (AFPO nanocage) could be a promising
      shortcut in clinical applications.

PMID- 29368507
TI  - Solid-State Synapse Based on Magnetoelectrically Coupled Memristor.
AB  - Brain-inspired computing architectures attempt to emulate the computations
      performed in the neurons and the synapses in the human brain. Memristors with
      continuously tunable resistances are ideal building blocks for artificial
      synapses. Through investigating the memristor behaviors in a
      La0.7Sr0.3MnO3/BaTiO3/La0.7Sr0.3MnO3 multiferroic tunnel junction, it was found
      that the ferroelectric domain dynamics characteristics are influenced by the
      relative magnetization alignment of the electrodes, and the interfacial spin
      polarization is manipulated continuously by ferroelectric domain reversal,
      enriching our understanding of the magnetoelectric coupling fundamentally. This
      creates a functionality that not only the resistance of the memristor but also
      the synaptic plasticity form can be further manipulated, as demonstrated by the
      spike-timing-dependent plasticity investigations. Density functional theory
      calculations are carried out to describe the obtained magnetoelectric coupling,
      which is probably related to the Mn-Ti intermixing at the interfaces. The
      multiple and controllable plasticity characteristic in a single artificial
      synapse, to resemble the synaptic morphological alteration property in a
      biological synapse, will be conducive to the development of artificial
      intelligence.

PMID- 29368508
TI  - Thermal Stability of Particle-Phase Monoethanolamine Salts.
AB  - The use of monoethanolamine (MEA, 2-hydroxyethanamine) for scrubbing of carbon
      dioxide from combustion flue gases may become the dominant technology for carbon
      capture in the near future. The widespread implementation of this technology will
      result in elevated emissions of MEA to the environment that may increase the
      loading and modify the properties of atmospheric aerosols. We have utilized
      experimental measurements together with aerosol microphysics calculations to
      derive thermodynamic properties of several MEA salts, potentially the dominant
      forms of MEA in atmospheric particles. The stability of the salts was found to
      depend strongly on the chemical nature of the acid counterpart. The saturation
      vapor pressures and vaporization enthalpies obtained in this study can be used to
      evaluate the role of MEA in the aerosol and haze formation, helping to assess
      impacts of the MEA-based carbon capture technology on air quality and climate
      change.

PMID- 29368509
TI  - Zearalenone Uptake and Biotransformation in Micropropagated Triticum durum Desf.
      Plants: A Xenobolomic Approach.
AB  - A model was set up to elucidate the uptake, translocation, and metabolic fate of
      zearalenone (ZEN) in durum wheat. After treatment with ZEN, roots and shoots were
      profiled with LC-HRMS. A comprehensive description of in planta ZEN
      biotransformation and a biotechnological evaluation of the model were obtained.
      Up to 200 MUg ZEN were removed by each plantlet after 14 days. Most ZEN and its
      masked forms were retained in roots, while minimal amounts were detected in
      leaves. Sixty-two chromatographic peaks were obtained, resulting in 7 putative
      phase I and 18 putative phase II metabolites. ZEN16Glc and ZEN14Glc were most
      abundant in roots, sulfo-conjugates and zearalenol derivatives were unable to
      gain systemic distribution, while distinct isomers of malonyl conjugates were
      found in leaves and roots. This study underlines the potential ZEN occurrence in
      plants without an ongoing Fusarium infection. Micropropagation may represent a
      tool to investigate the interplay between mycotoxins and wheat.

PMID- 29368510
TI  - Lead-Catalyzed Aqueous Benzoylation of Carbohydrates with an Acyl Phosphate
      Ester.
AB  - Biochemical systems utilize adenylates of amino acids to aminoacylate the 3'
      terminal diols of tRNAs. The reactive acyl group of the biological acylation
      agent is a subset of the general class of acyl phosphate monoesters. Those
      compounds are relatively stable in aqueous solutions, and their alkyl esters are
      conveniently prepared. It has previously been shown that biomimetic reactions of
      acyl phosphate monoesters with diols and carbohydrates are promoted by lanthanide
      salts. However, they also promote hydrolysis of acyl phosphate reagents, and the
      overall yields are modest. An assessment of the catalytic potential of
      alternative Lewis acids reveals that lead ions may be more effective as catalysts
      than lanthanides. Treatment of carbohydrates with benzoyl methyl phosphate (BMP)
      and triethylamine in water with added lead nitrate produces monobenzoyl esters in
      up to 75% yield. This provides a water-compatible pathway for novel patterns of
      benzoylation of polyhydroxylic compounds.

PMID- 29368511
TI  - Peptidoglycan Compositional Analysis of Enterococcus faecalis Biofilm by Stable
      Isotope Labeling by Amino Acids in a Bacterial Culture.
AB  - Peptidoglycan (PG) is a major component of the cell wall in Enterococcus
      faecalis. Accurate analysis of PG composition provides crucial insights into the
      bacterium's cellular functions and responses to external stimuli, but this
      analysis remains challenging because of various chemical modifications to PG
      repeat subunits. We characterized changes to the PG composition of E. faecalis
      grown as planktonic bacteria and biofilm by developing "stable isotope labeling
      by amino acids in bacterial culture" (SILAB), optimized for bacterial cultures
      with incomplete amino acid labeling. This comparative analysis by mass
      spectrometry was performed by labeling E. faecalis in biofilm with heavy Lys (l
      [13C6,2D9,15N2]Lys) and planktonic bacteria with natural abundance l-Lys, then
      mixing equal amounts of bacteria from each condition, and performing cell wall
      isolation and mutanolysin digestion necessary for liquid chromatography and mass
      spectrometry. An analytical method was developed to determine muropeptide
      abundances using correction factors to compensate for incomplete heavy Lys
      isotopic enrichment (98.33 +/- 0.05%) and incorporation (83.23 +/- 1.16%). Forty
      seven pairs of PG fragment ions from isolated cell walls of planktonic and
      biofilm samples were selected for SILAB analysis. We found that the PG in biofilm
      showed an increased level of PG cross-linking, an increased level of N
      deacetylation of GlcNAc, a decreased level of O-acetylation of MurNAc, and an
      increased number of stem modifications by d,d- and l,d-carboxypeptidases.

PMID- 29368513
TI  - Highly Localized Charge Transfer Excitons in Metal Oxide Semiconductors.
AB  - The ability to observe charge localization in photocatalytic materials on the
      ultrafast time scale promises to reveal important correlations between excited
      state electronic structure and photochemical energy conversion. Of particular
      interest is the ability to determine hole localization in the hybridized valence
      band of transition metal oxide semiconductors. Using femtosecond extreme
      ultraviolet reflection absorption (XUV-RA) spectroscopy we directly observe the
      formation of photoexcited electrons and holes in Fe2O3, Co3O4, and NiO occurring
      within the 100 fs instrument response. In each material, holes localize to the O
      2p valence band states as probed at the O L1-edge, while electrons localize to
      metal 3d conduction band states on this same time scale as probed at the metal
      M2,3-edge. Chemical shifts at the O L1-edge enable unambiguous comparison of
      metal-oxygen (M-O) bond covalency. Pump flux dependent measurements show that the
      exciton radius is on the order of a single M-O bond length, revealing a highly
      localized nature of exciton in each metal oxide studied.

PMID- 29368512
TI  - Facilitated Unbinding via Multivalency-Enabled Ternary Complexes: New Paradigm
      for Protein-DNA Interactions.
AB  - Dynamic protein-DNA interactions constitute highly robust cellular machineries to
      fulfill cellular functions. A vast number of studies have focused on how DNA
      binding proteins search for and interact with their target DNA segments and on
      what cellular cues can regulate protein binding, for which protein concentration
      is a most obvious one. In contrast, how protein unbinding could be regulated by
      protein concentration has evaded attention because protein unbinding from DNA is
      typically a unimolecular reaction and thus concentration independent. Recent
      single-molecule studies from multiple research groups have uncovered that protein
      concentration can facilitate the unbinding of DNA-bound proteins, revealing
      regulation of protein unbinding as another mechanistic paradigm for gene
      regulation. In this Account, we review these recent in vitro and in vivo single
      molecule experiments that uncovered the concentration-facilitated protein
      unbinding by multiple types of DNA-binding proteins, including sequence
      nonspecific DNA-binding proteins (e.g., nucleoid-associated proteins, NAP),
      sequence-specific DNA-binding proteins (e.g., metal-responsive transcription
      regulators CueR and ZntR), sequence-neutral single-stranded DNA-binding proteins
      (e.g., Replication protein A, RPA), and DNA polymerases. For the in vitro
      experiments, Marko's group investigated the exchange of GFP-tagged DNA-bound NAPs
      with nontagged NAPs in solution of increasing concentration using single-molecule
      magnetic-tweezers fluorescence microscopy. The faster fluorescence intensity
      decrease with higher nontagged NAP concentrations suggests that DNA-bound NAPs
      undergo faster exchange with higher free NAP concentrations. Chen's group used
      single-molecule fluorescence resonance energy transfer measurements to study the
      unbinding of CueR from its cognate oligomeric DNA. The average microscopic dwell
      times of DNA-bound states become shorter with increasing CueR concentrations in
      the surroundings, demonstrating that free CueR proteins can facilitate the
      unbinding of the incumbent one on DNA through either assisted dissociation or
      direct substitution. Greene's group studied the unbinding of RPAs from single
      stranded DNA using total internal reflection fluorescence microscopy and DNA
      curtain techniques. The fluorescence intensity versus time traces show faster
      decay with higher wild-type RPA concentrations, indicating that DNA-bound RPAs
      can undergo a concentration-facilitated exchange when encountering excess free
      RPA. van Oijen's group investigated the leading/lagging-strand polymerase
      exchange events in the bacteriophage T7 and E. coli replication systems using a
      combination of single-molecule fluorescence microscopy and DNA-flow-stretching
      assay. The processivity was observed to have larger decrease when the
      concentration of the Y526F polymerase mutant increases, indicating that the
      unbinding of the polymerase is also concentration-dependent. Using stroboscopic
      imaging and single-molecule tracking, Chen's group further advanced their study
      into living bacterial cells. They found CueR, as well as its homologue ZntR,
      shows concentration-enhanced unbinding from its DNA-binding site in vivo.
      Mechanistic consensus has emerged from these in vitro and in vivo single-molecule
      studies that encompass a range of proteins with distinct biological functions. It
      involves multivalent contacts between protein and DNA. The multivalency enables
      the formation of ternary complexes as intermediates, which subsequently give rise
      to concentration-enhanced protein unbinding. As multivalent contacts are
      ubiquitous among DNA-interacting proteins, this multivalency-enabled facilitated
      unbinding mechanism thus provides a potentially general mechanistic paradigm in
      regulating protein-DNA interactions.

PMID- 29368514
TI  - Ratiometric Phosphorescent Probe for Thallium in Serum, Water, and Soil Samples
      Based on Long-Lived, Spectrally Resolved, Mn-Doped ZnSe Quantum Dots and Carbon
      Dots.
AB  - Thallium (Tl) is an extremely toxic heavy metal and exists in very low
      concentrations in the environment, but its sensing is largely underexplored as
      compared to its neighboring elements in the periodic table (especially mercury
      and lead). In this work, we developed a ratiometric phosphorescent nanoprobe for
      thallium detection based on Mn-doped ZnSe quantum dots (QDs) and water-soluble
      carbon dots (C-dots). Upon excitation with 360 nm, Mn-doped ZnSe QDs and C-dots
      can emit long-lived and spectrally resolved phosphorescence at 580 and 440 nm,
      respectively. In the presence of thallium, the phosphorescence emission from Mn
      doped ZnSe QDs could be selectively quenched, while that from C-dots retained
      unchanged. Therefore, a ratiometric phosphorescent probe was thus developed,
      which can eliminate the potential influence from both background fluorescence and
      other analyte-independent external environment factors. Several other heavy metal
      ions caused interferences to thallium detection but could be efficiently masked
      with EDTA. The proposed method offered a detection limit of 1 MUg/L, which is
      among the most sensitive probes ever reported. Successful application of this
      method for thallium detection in biological serum as well as in environmental
      water and soil samples was demonstrated.

PMID- 29368515
TI  - Single-Crystal Graphene-Directed van der Waals Epitaxial Resistive Switching.
AB  - Graphene has been broadcasted as a promising choice of electrode and substrate
      for flexible electronics. To be truly useful in this regime, graphene has to
      prove its capability in ordering the growth of overlayers at an atomic scale,
      commonly known as epitaxy. Meanwhile, graphene as a diffusion barrier against
      atoms and ions has been shown in some metal-graphene-dielectric configurations
      for integrated circuits. Guided by these two points, this work explores a new
      direction of using graphene as a bifunctional material in an electrochemical
      metallization memory, where graphene is shown to (i) order the growth of a low
      ionicity semiconductor ZnS single-crystalline film and (ii) regulate the ion
      migration in the resistive switching device made of Cu/ZnS/graphene/Cu
      structures. The ZnS film is confirmed to be van der Waals epitaxially grown on
      single-crystal graphene with X-ray structural analysis and Raman spectroscopy.
      Charge transport studies with controlled kinetic parameters reveal superior ion
      regulating characteristic of graphene in this ZnS-based resistive switching
      device. The demonstration of the first graphene-directed epitaxial wide band gap
      semiconductor resistive switching suggests a possible and promising route toward
      flexible memristors.

PMID- 29368516
TI  - A Switchable Helical Capsule for Encapsulation and Release of Potassium Ion.
AB  - A type of aromatic helical capsules was synthesized. The crystal structure proved
      an inner cavity that could perform switchable encapsulation and release of
      potassium ion through protonation/deprotonation-mediated extension and
      contraction of molecular motion.

PMID- 29368517
TI  - Exploring Microbial Peptidases for Cheese Production: A Viewpoint on the Current
      Conjecture.

PMID- 29368518
TI  - Activating TiO2 Nanoparticles: Gallium-68 Serves as a High-Yield Photon Emitter
      for Cerenkov-Induced Photodynamic Therapy.
AB  - The classical photodynamic therapy (PDT) requires external light to activate
      photosensitizers for cancer treatment. However, limited tissue penetration of
      light has been a long-standing challenge for PDT to cure malignant tumors in deep
      tissues. Recently, Cerenkov radiation (CR) emitted by radiotracers such as 18F
      fluorodeoxyglucose (18F-FDG) has become an alternative and promising internal
      light source. Nevertheless, fluorine-18 (F-18) only releases 1.3 photons per
      decay in average; consequently, injection dose of F-18 goes beyond 10-30 times
      more than usual to acquire therapeutic efficacy because of its low Cerenkov
      productivity. Gallium-68 (Ga-68) is a favorable CR source owing to its ready
      availability from generator and 30-time higher Cerenkov productivity. Herein, we
      report, for the first time, the use of Ga-68 as a CR source to activate dextran
      modified TiO2 nanoparticles (D-TiO2 NPs) for CR-induced PDT. Compared with 18F
      FDG, 68Ga-labeled bovine serum albumin (68Ga-BSA) inhibited the growth of 4T1
      cells and exhibited significantly stronger DNA damage to tumor cells. In vivo
      studies showed that the tumor growth was almost completely inhibited when tumor
      bearing mice were treated with a combination of D-TiO2 NPs and 68Ga-BSA. This
      study proved that Ga-68 is a more potent radionuclide for PDT than F-18 both in
      vitro and in vivo offered a promising strategy of using a diagnostic dose of
      radioactivity to achieve depth-independent cancer therapy without using any
      external light source.

PMID- 29368519
TI  - Metallic Ti3C2Tx MXene Gas Sensors with Ultrahigh Signal-to-Noise Ratio.
AB  - Achieving high sensitivity in solid-state gas sensors can allow the precise
      detection of chemical agents. In particular, detection of volatile organic
      compounds (VOCs) at the parts per billion (ppb) level is critical for the early
      diagnosis of diseases. To obtain high sensitivity, two requirements need to be
      simultaneously satisfied: (i) low electrical noise and (ii) strong signal, which
      existing sensor materials cannot meet. Here, we demonstrate that 2D metal carbide
      MXenes, which possess high metallic conductivity for low noise and a fully
      functionalized surface for a strong signal, greatly outperform the sensitivity of
      conventional semiconductor channel materials. Ti3C2Tx MXene gas sensors exhibited
      a very low limit of detection of 50-100 ppb for VOC gases at room temperature.
      Also, the extremely low noise led to a signal-to-noise ratio 2 orders of
      magnitude higher than that of other 2D materials, surpassing the best sensors
      known. Our results provide insight in utilizing highly functionalized metallic
      sensing channels for developing highly sensitive sensors.

PMID- 29368520
TI  - Sensitive Detection of RNase A Activity and Collaborative Drug Screening Based on
      rGO and Fluorescence Probe.
AB  - In addition to being an important object in theoretical and experimental studies
      in enzymology, RNase A also plays an important role in the development of many
      kinds of diseases by regulating various physiological or pathological processes,
      including cell growth, proliferation, differentiation, and invasion. Thus, it can
      be used as a useful biomarker for disease theranostics. Here, a simple,
      sensitive, and low-cost assay for RNase A was constructed by combining a
      fluorogenic substrate with reduced graphene oxide (rGO). The method with
      detection limit of 0.05 ng/mL was first applied for RNase A targeted drug
      screening, and 14 natural compounds were identified as activators of this enzyme.
      Then, it was applied to detect the effect of drug treatment and Hepatitis B virus
      (HBV) infection on RNase A activity. The results indicated that RNase A level in
      tumor cells was upregulated by G-10 and Chikusetsusaponin V in a concentration
      dependent manner, while the average level of RNase A in the HBV infection group
      was significantly inhibited compared with that in the control group. Furthermore,
      the concentration-dependent inhibitory effect of heavy metal ions on RNase A was
      observed using the method and the results indicated that Ba2+, Co2+, Pb2+, As3+,
      and Cu2+ inhibited RNase A activity with IC50 values of 93.7 MUM (Ba2+), 90.9 MUM
      (Co2+), 110.6 MUM (Pb2+), 171.5 MUM (As3+), and 165.1 MUM (Cu2+), respectively.
      In summary, considering the benefits of rapidity and high sensitivity, the method
      is practicable for RNase A assay in biosamples and natural compounds screening in
      vitro and in vivo.

PMID- 29368521
TI  - Deciphering Functions of Intracellular Formaldehyde: Linking Cancer and Aldehyde
      Metabolism.

PMID- 29368522
TI  - Metal-Phosphate Bilayers for Anatase Surface Modification.
AB  - Compared to many other metal oxides, anatase TiO2 shows relatively lower
      reactivity toward carboxylic acid anchor groups. The latter is crucial for
      applications, for example, in dye-sensitized solar cells (DSSCs), where the most
      used dyes bind to the metal oxide surface through carboxylic acid terminations.
      To improve the surface reactivity, metal-phosphate bilayers of Ni or Co were
      synthesized on anatase TiO2 compact oxide and nanotubes. In both cases, time-of
      flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron
      spectroscopy (XPS) results showed that the bilayers were successfully formed and
      that the phosphate layer works as an intermediate between TiO2 and the other
      species. ToF-SIMS depth profiles of modified nanotubes showed that Ni and Co are
      present through the whole tube length and reduce in content after heat treatment,
      in agreement with XPS results. Phosphate groups, on the other hand, are more
      present in the tubes' depth, and their content on the surface is reduced upon
      exposure to temperature. The reactivity of the modified surfaces toward
      carboxylic acid-terminated molecules, as stearic acid and Ru-based N719 dye, was
      evaluated. Contact angle measurements together with dye desorption experiments
      demonstrated that the Co-phosphate bilayers heat-treated at 300  degrees C
      resulted in the largest enhancement compared to the reference. Bilayer-modified
      compact anatase TiO2 and anatase TiO2 nanotubes were utilized as photoanodes in
      DSSCs. An increase in efficiency was observed for all modified electrodes with
      phosphate-Co treatment, leading to the highest JSC values and an efficiency
      improvement of 48%.

PMID- 29368523
TI  - [Changes in pathology since the times of Purkinje].
AB  - The discipline of pathology was founded in the Purkinje era on the principles of
      building scientific knowledge of diseases through co-operation among clinical
      specialists. During the 20th century the focus of pathologists work has
      progressed from autopsies to biopsy diagnostics. The discipline of
      histopathological and cytopathological biopsy took form and continuously
      incorporates new methodologies and new standards. Its future course compels us to
      reflect on the changing requirements of clinical medicine. Current undergraduate
      education programs are directed toward forming a basis of expertise for both
      clinicians and non-medical healthcare professionals. At the postgraduate level
      and in research we are seeing an ever-closer interdisciplinary link, especially
      within the fields of genetics. This approach brings pathological processes to a
      new level, but also demands new levels of knowledge. Through comprehensive
      diagnostic experience, both prognostic and predictive, a pathologist is an
      indispensable member of the diagnostic and therapeutic team.

PMID- 29368524
TI  - [The contemporary view of the cardiac conduction system].
AB  - Cardiac conduction system was described in its complete form in homeotherm
      vertebrates 110 years ago. Despite this fact, many new findings concerning its
      specification and development that have an impact on its pacemaking and
      conducting function appeared in the past decade. Conduction system disorders are
      associated with arrhythmias, and some of which have a developmental origin.
      Evolutionary view on this area is particularly useful for better understanding of
      the atrioventricular canal remodelling.

PMID- 29368525
TI  - [Data analysis: challenges and specifics in neuroscience and psychiatry].
AB  - The amount of available data relevant for clinical decision support is rising not
      only rapidly but at the same time much faster than our ability to analyze and
      interpret them. Thus, the potential of the data to contribute to determining the
      diagnosis, therapy and prognosis of an individual patient is not appropriately
      exploited. The hopes to obtain benefit from the data for an individual patient
      must be accompanied by a reliable and diligent biostatistical analysis which
      faces serious challenges not always clear to non-statisticians. The aim of this
      paper is to discuss principles of statistical analysis of big data in research
      and routine applications in clinical medicine, focusing on particular aspects of
      psychiatry. The paper brings arguments in favor of the idea that the
      biostatistical analysis of data in a specialty field requires different
      approaches and different experience compared to other clinical fields. This is
      illustrated by a description of common complications of the analysis of
      psychiatric data. Challenges of the analysis of big data in both psychiatric
      research and routine practice are explained, which are far from a routine service
      activity exploiting standard methods of multivariate statistics and/or machine
      learning. Important research questions, which are important in the current
      psychiatric research, are presented and discussed from the biostatistical point
      of view.

PMID- 29368526
TI  - [Secondary symptoms of disability in international studies].
AB  - The overview study deals with the secondary conditions in individuals with
      disability. In the framework of the overview study 24 researches (1984-2016) were
      analyzed. According to the researches, individuals with disabilities are exposed
      to several secondary conditions such as obesity, pressure sores, metabolic
      imbalance, pain, fatigue, depression and others. Secondary conditions have been
      observed mainly in individuals with physical disability. The most frequently used
      research approach was a quantitative research strategy based on the form of a
      questionnaire. The range of research sample differs among selected studies.
      Smallest research sample consisted of 71 respondents, the largest of 3076
      respondents. Secondary symptoms of disability may be perceived as less serious
      problems, however their presence and cumulation can significantly decrease the
      quality of life of people with disabilities.

PMID- 29368527
TI  - [New ways towards the improvement of the seniors health literacy].
AB  - The elderly population is one of the vulnerable groups due to their low health
      literacy. Health literacy represents a way of effective ensuring, comprehension
      and utilization of health information to be able to make the best possible
      decisions in the care of one's health. The presented systematic overview study
      was compiled using the analysis of 38 database publications. The goal was to find
      relevant resources concerning the relation between health literacy and compliance
      in the treatment of adult and elderly individuals. Another goal was to describe
      the influence of tools and the possibility of using e-health to improve the
      seniors' health literacy. The source analysis proves that limited health literacy
      correlates with the decrease of cognitive functions. Some studies show that
      health literacy directly correlates with the level of education and age. The
      elderly individuals who show higher health literacy observe their doctors' advice
      more frequently and are, moreover, active recipients of health care. One of the
      tools of how to improve health literacy is e-health technology using internet,
      mobile phones, tablets or other information media.Key words: health literacy,
      health care, patient, senior, compliance, e-health.

PMID- 29368528
TI  - [Traditional medicine and the present: the therapy of gout].
AB  - The authors describe the history of treatment of gout by using colchicine
      (colchicum; the active substance of Colchicum autumnale). The references to this
      plant and its effects (incl. several recipes for the preparation of remedies) in
      the gout treatment date back already from the antiquity, but the indisputable
      evidence of its use in the therapy of the disease in question comes only from the
      6th century AD, by Alexander of Tralles. At present, colchicine became an
      officially preferred drug. Some other examples of medicines of plant origin (e.g.
      verbena), which were used already by ancient civilizations and are often chosen
      for therapy even today. The potential of medicinal drugs hasnt been completely
      exhausted yet.

PMID- 29368529
TI  - Value of two-cycle docetaxel, cisplatin, and 5-fluorouracil induction
      chemotherapy in hypopharyngeal carcinoma.
AB  - Various studies have investigated laryngeal function and survival after induction
      chemotherapy in hypopharyngeal carcinoma, but potential factors to help predict
      response rates after induction chemotherapy remain unknown. This retro- spective
      study evaluated which factors are related to an ineffective response to two-cycle
      docetaxel, cisplatin, and 5-fluoro- uracil (TPF) induction chemotherapy in
      hypopharyngeal carcinoma to determine potential candidates for this treatment in
      clinical practice. From Jan 2005 to Dec 2015, 81 patients diagnosed with
      hypopharyngeal squamous cell carcinoma based on a pathological examination were
      analyzed. They were administered two-cycle TPF induction chemotherapy, and
      magnetic resonance imaging was performed before and after induction chemotherapy.
      The mean survival time was 5.7 years (95% confidence interval, 5.1-6.2 years).
      The 1, 3, 5 and 6-year survival rates were 98.8%, 80.1%, 64.5%, and 54.2%,
      respectively. TPF induction chemotherapy was well tolerated; the main adverse
      effects resolved with symptomatic treatment. A response to TPF induction
      chemotherapy was associated with lymph node size, tumor grade, invasion region, T
      stage, and primary tumor. The following issues were significantly associated with
      an increasing non-response rate to two-cycle induction chemotherapy: increasing
      lymph node size, moderately differentiated squamous cell carcinoma, invasion of
      the esophagus along with the thyroid cartilage, and primary tumor in the piriform
      sinus. Lymph nodes of >=2.15 cm, moderately differenti- ated tumor grade, or
      thyroid cartilage invasion were the best cutoff values for patients who did not
      respond to induction chemotherapy. However, the initial cancer site, cancer
      stage, and degree of cancer differentiation were not closely related to the
      efficacy of induction chemotherapy.

PMID- 29368530
TI  - Physiological, Perceptual, and Affective Responses to Six High-Intensity Interval
      Training Protocols.
AB  - This study examined the extent to which different high-intensity interval
      training (HIIT) and sprint interval training (SIT) protocols could influence
      psychophysiological responses in moderately active young men. Fourteen
      participants completed, in a randomized order, three cycling protocols (SIT: 4 *
      30-second all-out sprints; Tabata: 7 * 20 seconds at 170% ?O2max; and HIIT: 10 *
      60 seconds at 90% HRmax) and three running HIIT protocols (4 * 4 minutes at 90%
      95% HRmax, 5 * at v?O2max, and 4 * 1,000 meters at a rating of perceived exertion
      (RPE) of 8, from the OMNI-Walk/Run scale). Oxygen uptake (?O2), heart rate, and
      RPE were recorded during each interval. Affective responses were assessed before
      and after each trial. The Tabata protocol elicited the highest ?O2 and RPE
      responses, and the least pleasant session-affect among the cycling trials. The
      v?O2max elicited the highest ?O2 and RPE responses and the lowest mean session
      affect among the running trials. Findings highlight the limited application of
      SIT and some HIIT protocols to individuals with low fitness levels.

PMID- 29368531
TI  - Exploratory study of the dispensing patterns of vaccines by a sample of community
      pharmacies in Southern Africa.
AB  - INTRODUCTION: Vaccination is one of the most cost-effective healthcare
      interventions. Pharmacies in South Africa provide a vaccination service where
      childhood immunizations, some travel vaccines and vaccines for specific
      populations are dispensed and administered, but little has been published on
      which vaccines are dispensed and at what cost. Areas covered: This retrospective
      drug utilization study determined the dispensing patterns of vaccines in
      community pharmacies during 2015 with the focus on the types and cost of vaccines
      dispensed in ATC group J07. Expert commentary: Of the 140 902 vaccines dispensed
      to 79 415 patients, viral vaccines (J07B) accounted for most of the prescriptions
      (82.7% of volume; 62.3% of cost), followed by bacterial vaccines (J07A) (17.1% of
      volume; 37.5% of cost), and bacterial and viral vaccines combined (0.2% of
      volume; 0.3% of cost). There was an increase in the dispensing patterns of viral
      vaccines (J07B) in the period just before the winter months. Half of all vaccines
      (50.4%) were for the influenza vaccine (J07BB01). This vaccine accounted for only
      15.6% of the total cost of vaccines. The most expensive vaccines were
      pneumococcal polysaccharide conjugate vaccine (13-valent adsorbed, pre-filled
      syringe) (J07AL01), followed by human papillomavirus bivalent vaccine (J07BM02).

PMID- 29368533
TI  - Keys to person-centred care to persons living with dementia - Experiences from an
      educational program in Sweden.
AB  - Growing old entails an increased risk of disabilities and illnesses such as
      dementia. The orientation in Sweden on national level is that individuals remain
      in their own homes if desired and receive person-centred home care. The aim of
      this study was to describe the experience of an educational program and its
      influence on daily provision of care to persons with dementia. A life-world
      approach was used. Data were collected through group interviews with care
      providers in the context of home. The findings are presented in five themes:
      Increased knowledge about dementia and treatment, Relationship-building in order
      to provide good care, Open and flexible approach conveys calm, Continuity and
      flexibility are cornerstones in the care and Perceived improvements. This person
      centred educational intervention resulted in a care that was based on each
      individual's personality, preferences and priorities in life. Education given
      with continuity over time is key to improving provision of care to person with
      dementia.

PMID- 29368534
TI  - Patient-satisfaction in an outpatient vein surgery office: A comparison of
      English- and Spanish-speaking patients.
AB  - BACKGROUND: In spite of an increasing Latino population and accompanying rise in
      demand for health care, not much is known about patient-satisfaction in Spanish
      speaking patients and how to improve patient-satisfaction when using
      interpreters. We sought to compare patient-satisfaction with vein surgery office
      visits between English-speaking and Spanish-speaking patients. METHODS: Directly
      before and after the office visit, 126 patients completed a socio-demographic
      survey, a five-point ordinal rating survey of physician and interpreter
      satisfaction with the encounter. Measures were satisfaction with the provider's
      friendliness, respectfulness, concern, ability to make the patient comfortable,
      and time spent for the exam. RESULTS: When the provider was fluent in the
      language that the patient spoke, patients ( M = 4.954, SD = 0.21) were
      significantly more satisfied with their visit at VVHC than patients who required
      an interpreter ( M = 4.762, SD = 0.71), z = 2.230, p = 0.012. Spanish speaking
      patients were more likely to be satisfied with the visit when they felt their
      interpreter was friendly ( n = 58, p = 0.049). There was no difference found with
      regard to the provider being thoughtful and comforting. CONCLUSION: Spanish
      speaking patients are less satisfied with the care provided in a vein surgery
      office. Patients who communicated through an interpreter were less satisfied with
      the patient-provider relationship. In light of the growing diversity of the US
      population and the fact that patient-satisfaction is increasingly tied to
      reimbursement, additional research might identify potential areas of improvement
      for the surgeon, interpreter, and patient perspectives.

PMID- 29368532
TI  - Image-enhanced endoscopy is specific for the diagnosis of non-erosive
      gastroesophageal reflux disease.
AB  - OBJECTIVES: We assessed the performance characteristics of image-enhanced
      endoscopy with i-Scan or narrow band imaging (NBI) in patients with non-erosive
      gastroesophageal reflux disease (GERD) compared to controls without heartburn.
      MATERIAL AND METHODS: Image-enhanced endoscopic findings of vascularity at the
      squamocolumnar junction, distal esophageal micro-erosions, and non-round pit
      pattern at the squamocolumnar junction were assessed in cases (heartburn not
      responsive to PPIs, positive results on validated GERD questionnaire, no
      esophageal erosions, esophageal biopsies with histologic evidence of GERD (basal
      cell hyperplasia, elongation of papillae and dilation of intercellular spaces all
      required)) and in controls (no GERD symptoms or esophageal erosions). RESULTS:
      Twenty cases and 60 controls were compared. The pre-defined features were more
      common in cases vs. CONTROLS: vascularity RR = 4.9 (95% CI: 2.4-10.0),
      specificity = 86.7%; micro-erosions RR = 9.7 (3.6-26.5), specificity = 93.3%; non
      round pit pattern RR = 2.4 (1.7-3.3), specificity = 60.0%; combination of
      vascularity and micro-erosions RR = 30.0 (4.1-220), specificity = 98.3%. These
      differences were consistent with both i-Scan and NBI. CONCLUSIONS: Image-enhanced
      endoscopic findings of vascularity and micro-erosions were very specific for non
      erosive GERD. Image-enhanced endoscopy may be useful in real-time diagnosis of
      non-erosive GERD when patients undergo upper endoscopy for heartburn. The
      relative utility of image-enhanced endoscopy vs. pH-impedance monitoring, based
      on efficacy, cost and patient acceptance, requires additional study.

PMID- 29368535
TI  - Retroperitoneal fibrosis as extramedullary hematopoiesis of a chronic
      myelomonocytic leukemia.

PMID- 29368536
TI  - Delayed migration of Squid 18 following embolisation of a direct carotico
      cavernous fistula.
AB  - We report a case of delayed migration of Squid 18 following treatment of a direct
      carotico-cavernous fistula.

PMID- 29368537
TI  - Superior Efficacy and Improved Renal and Bone Safety After Switching from a
      Tenofovir Disoproxil Fumarate- to a Tenofovir Alafenamide-Based Regimen Through
      96 Weeks of Treatment.
AB  - We previously demonstrated superior efficacy and safety advantages in HIV
      infected, virologically suppressed adults switched to a regimen containing
      tenofovir alafenamide (TAF) as compared with those remaining on a tenofovir
      disoproxil fumarate (TDF) regimen through week 48. We now report long-term data
      through week 96. In this randomized, active-controlled, multicenter, open-label,
      noninferiority trial (ClinicalTrials.gov No. NCT01815736), we randomized
      virologically suppressed (HIV-1 RNA <50 copies/ml) adults (2:1) to receive a once
      daily, single-tablet regimen containing elvitegravir (EVG), cobicistat (COBI),
      emtricitabine (FTC), and TAF group or to continue one of four TDF-containing
      regimens (TDF group) for 96 weeks. We evaluated efficacy (HIV-1 RNA <50 copies/ml
      using the FDA snapshot algorithm) and prespecified bone and renal endpoints at
      week 96. We randomized and treated 1,436 participants in this study (TAF n = 959,
      TDF n = 477). At week 96, TAF was superior to TDF in virologic efficacy, with 93%
      on TAF and 89% on TDF having HIV-1 RNA <50 copies/ml (difference 3.7%, 95%
      confidence interval: 0.4%-7.0%). Improvements in hip and spine bone mineral
      density for those assigned to TAF versus TDF continued through week 96 (p <
      .001). Significant improvements in urine protein or albumin to creatinine ratios
      were also seen among those in the TAF group versus TDF through week 96 (p <
      .001). There were no cases of investigator-reported proximal renal tubulopathy in
      the TAF group as compared with one case in the TDF group. Switching to
      EVG/COBI/FTC/TAF (E/C/F/TAF) was associated with statistically significant
      efficacy and safety advantages over remaining on a standard-of-care TDF-based
      regimen.

PMID- 29368538
TI  - The bone remodelling cycle.
AB  - The bone remodelling cycle replaces old and damaged bone and is a highly
      regulated, lifelong process essential for preserving bone integrity and
      maintaining mineral homeostasis. During the bone remodelling cycle, osteoclastic
      resorption is tightly coupled to osteoblastic bone formation. The remodelling
      cycle occurs within the basic multicellular unit and comprises five co-ordinated
      steps; activation, resorption, reversal, formation and termination. These steps
      occur simultaneously but asynchronously at multiple different locations within
      the skeleton. Study of rare human bone disease and animal models have helped to
      elucidate the cellular and molecular mechanisms that regulate the bone
      remodelling cycle. The key signalling pathways controlling osteoclastic bone
      resorption and osteoblastic bone formation are receptor activator of nuclear
      factor-kappaB (RANK)/RANK ligand/osteoprotegerin and canonical Wnt signalling.
      Cytokines, growth factors and prostaglandins act as paracrine regulators of the
      cycle, whereas endocrine regulators include parathyroid hormone, vitamin D,
      calcitonin, growth hormone, glucocorticoids, sex hormones, and thyroid hormone.
      Disruption of the bone remodelling cycle and any resulting imbalance between bone
      resorption and formation leads to metabolic bone disease, most commonly
      osteoporosis. The advances in understanding the cellular and molecular mechanisms
      underlying bone remodelling have also provided targets for pharmacological
      interventions which include antiresorptive and anabolic therapies. This review
      will describe the remodelling process and its regulation, discuss osteoporosis
      and summarize the commonest pharmacological interventions used in its management.

PMID- 29368539
TI  - Safety and efficacy of ADS-5102 (amantadine) extended release capsules to improve
      walking in multiple sclerosis: A randomized, placebo-controlled, phase 2 trial.
AB  - BACKGROUND: Walking impairment causes disability and reduced quality of life in
      patients with multiple sclerosis (MS). OBJECTIVE: Characterize the safety and
      efficacy of ADS-5102 (amantadine) extended release capsules, 274 mg administered
      once daily at bedtime in patients with MS with walking impairment. METHODS: This
      randomized, double-blind, placebo-controlled, 4-week study was conducted at 14
      trial sites in the United States. Study objectives included safety and
      tolerability of ADS-5102, and efficacy assessments (Timed 25-Foot Walk (T25FW),
      Timed Up and Go (TUG), 2-Minute Walk Test, and Multiple Sclerosis Walking Scale
      12). Fatigue, depression, and cognition also were assessed. RESULTS: A total of
      60 patients were randomized (30 to ADS-5102 and 30 to placebo); 59 of whom were
      treated. The most frequent adverse events (AEs) were dry mouth, constipation, and
      insomnia. Five ADS-5102 patients and no placebo patients discontinued treatment
      due to AEs. One patient in the ADS-5102 group experienced a serious AE-suspected
      serotonin syndrome. A 16.6% placebo-adjusted improvement was seen in the T25FW
      test ( p < 0.05). A 10% placebo-adjusted improvement in TUG was also observed. No
      changes in fatigue, depression, or cognition were observed. CONCLUSION: ADS-5102
      was generally well tolerated. These data demonstrate an effect of ADS-5102 on
      walking speed. Further studies are warranted to confirm these observations.

PMID- 29368540
TI  - High-quality low-dose cardiovascular computed tomography (CCT) in pediatric
      patients using a 64-slice scanner.
AB  - Background Cardiovascular computed tomography (CCT) technology is rapidly
      advancing allowing to perform good quality examinations with a radiation dose as
      low as 1.2 mSv. However, latest generation scanners are not available in all
      centers. Purpose To estimate radiation dose and image quality in pediatric CCT
      using a standard 64-slice scanner. Material and Methods A total of 100 patients
      aged 6.9 +/- 5.4 years (mean +/- standard deviation) who underwent a 64-slice CCT
      scan using 80, 100, or 120 kVp, were retrospectively evaluated. Radiation
      effective dose was calculated on the basis of the dose length product. Two
      independent readers assessed the image quality through signal-to-noise ratio
      (SNR), contrast-to-noise ratio (CNR), and a qualitative score (3 = very good, 2 =
      good, 1 = poor). Non-parametric tests were used. Results Fifty-five exams were
      not electrocardiographically (ECG) triggered, 20 had a prospective ECG
      triggering, and 25 had retrospective ECG triggering. The median effective dose
      was 1.3 mSv (interquartile range [IQR] = 0.8-2.7 mSv). Median SNR was 30.6 (IQR =
      23.4-33.6) at 120 kVp, 29.4 (IQR = 23.7-34.8) at 100 kVp, and 24.7 (IQR = 19.4
      34.3) at 80 kVp. Median CNR was 21.0 (IQR = 14.8-24.4), 19.1 (IQR = 15.6-23.9),
      and 25.3 (IQR = 19.4-33.4), respectively. Image quality was very good, good, and
      poor in 56, 39, and 5 patients, respectively. No significant differences were
      found among voltage groups for SNR ( P = 0.486), CNR ( P = 0.336), and subjective
      image quality ( P = 0.296). The inter-observer reproducibility was almost perfect
      (kappa = 0.880). Conclusion High-quality pediatric CCT can be performed using a
      64-slice scanner, with a radiation effective dose close to 2 mSv in about 50% of
      the cases.

PMID- 29368541
TI  - Double hit lymphoma: do we need a 'double hit' of intensive therapy?

PMID- 29368543
TI  - Development of novel biofunctionalized chitosan decorated nanocochleates as a
      cancer targeted drug delivery platform.
AB  - A new family of biofunctionalized chitosan decorated nanocochleates-mediated drug
      delivery system was developed that involves uniquely combining nanocochleates
      with anticancer drug for controlled drug release, targeted delivery, improved
      bioavailability with reduced toxicity. This system was developed by loading of
      doxorubicin (DOX) to nanocochleates (DOX-NC) through conversion of negatively
      charged dimyristoylphosphatidylcholine (DMPC) phospholipid and cholesterol
      bearing vesicles on addition of calcium ions, followed by encapsulation DOX-NC
      with folic acid conjugated chitosan (FA-CHI-DOX-NC). The release of DOX indicated
      strong pH dependence and implies hydrogen-bonding interaction between
      nanocochleates and DOX. Formulated FA-CHI-DOX-NC demonstrated higher in-vitro
      anticancer activity in folate overexpressed human breast cancer MCF-7 cells. The
      targeting effect for the FA-CHI-DOX-NC was also demonstrated. The concentration
      of the drug needed for growth inhibition of 50% of cells in a designed time
      period (GI50) was 9.1 ug/ml for DOX while it was decreased by 31.68% for the DOX
      NC (6.2 ug/ml). Furthermore, the GI50 value of FA-CHI-DOX-NC was 4.4 ug/ml, i.e.
      a 51.64% decrease was observed as compared to DOX solution. Moreover,
      bioavailability of DOX from FA-CHI-DOX-NC increased by 4-fold with long
      circulation time, slower plasma elimination and no sign of tissue toxicity as
      compared to DOX solution. The proposed strategy is advantageous in terms of
      targeted drug delivery and has high potential to address the current challenges
      in drug delivery. Thus, the prepared new carrier offers a novel formulation that
      combines the unique properties of a biodegradable material, chitosan and
      nanocochleates for biomedical applications.

PMID- 29368542
TI  - miR-448 inhibits the epithelial-mesenchymal transition in breast cancer cells by
      directly targeting the E-cadherin repressor ZEB1/2.
AB  - Recently, accumulating evidence provides that dysregulation of microRNAs (miRNAs)
      is considered to play vital roles in tumor progression. Based on microRNA arrays,
      we found that microRNA-448 (miR-448) was significantly downregulated in breast
      cancer tissue specimens. In our study, we were in an effort to clarify the
      function, the direct target gene, and the molecular mechanisms of miR-448 in
      breast cancer. By quantitative RT-PCR, we analyzed the expression of miR-448 in
      16 patients with BC. Overexpression of miR-448 was established by transfecting
      miR-448-mimics into MDA-MB-231 and MCF-7 cells, methyl thiazolyl- tetrazolium and
      colony formation assays were performed to evaluate its effects on cell
      proliferation. We also performed cell migration and invasion assays in breast
      cells overexpressing miRNA-448. All the results indicated that overexpression of
      miR-448 in breast cancer cells markedly suppressed cell proliferation, migration,
      and invasion. Through the quantitative RT-PCR and Western Blots, we also
      evaluated epithelial-mesenchymal transition. We found that overexpression of miR
      448 also downregulated the expression of vimentin, a well-known mesenchymal
      marker. Meanwhile, the epithelial marker E-cadherin was unregulated, suggesting
      that miR-448 inhibited epithelial-mesenchymal transition . Bioinformatics assay
      coupled with Western Blot and luciferase assays revealed that miR-448 directly
      binds to the 3'UTR of E-cadherin repressor ZEB1/2, resulting in suppression of
      epithelial-mesenchymal transition in breast cancer cells. Impact statement In our
      study, we revealed that miR-448 played a vital role in breast cancer development
      and we also uncovered the mechanisms of it. Following is the short description of
      the main findings: miR-448 is downregulated in BC. miR-448 regulates cell
      proliferation, migration, and invasion in BC. miR-448 specifically regulates
      ZEB1/2  through binding to the 3'UTR in BC cells. miR-448 inhibits cell
      migration, invasion,  and EMT by targeting to the 3'UTR of  ZEB1/2.

PMID- 29368545
TI  - Affective Responses to Acute Bouts of Aerobic Exercise, Mindfulness Meditation,
      and Combinations of Exercise and Meditation: A Randomized Controlled
      Intervention.
AB  - Single bouts of aerobic exercise and meditation have been shown to induce
      positive affect. In a novel experimental paradigm, we sought to examine the
      effects of an acute bout of aerobic exercise and meditation, as well as exercise
      and meditation combined on affect among young adults. Participants ( N = 110,
      mean age = 21.4 years) were randomly assigned to walk, meditate, walk then
      meditate, meditate then walk, or to sit (inactive control). All walking and
      meditation bouts were 10 minutes in duration. Participants' affect was monitored
      before and after the intervention using the Exercise Induced Feelings Inventory.
      Significant group * time interaction effects were observed for three Exercise
      Induced Feelings Inventory subscales, including revitalization ( p < .001),
      tranquility ( p = .02), and exhaustion ( p = .03); the group * time interaction
      for Exercise Induced Feelings Inventory positive engagement was nonsignificant (
      p = .16). A single bout of brisk walking or meditation, as well as a combination
      of walking and meditation, may positively influence affect. There is some
      evidence to suggest that affective benefits may be greater following meditation
      or a combination of meditation and walking, when compared with walking alone.

PMID- 29368544
TI  - Feasibility of endoscopic submucosal dissection for cecal lesions.
AB  - BACKGROUND: The treatment results of endoscopic submucosal dissection (ESD) for
      colorectal lesions have improved markedly, but some lesions remain difficult to
      treat. Hence the cecum is considered a technically challenging site for ESD. We
      examined the feasibility of ESD for cecal lesions. METHODS: Among a total of 708
      colorectal ESD performed in our hospital between March 2006 and December 2016,
      549 procedures performed after April 2012 were studied, at a time when the
      techniques of ESD had stabilized and the procedure was covered by health
      insurance in Japan. Among 549 cases, 61 were cecal lesions and 488 were noncecal
      lesions. The treatment outcomes were analyzed. RESULTS: For cecal lesions, the en
      bloc resection rate was 95.1%, R0 resection rate was 91.8%, perforation rate was
      0%, delayed bleeding rate was 6.6%, median diameter of resected specimen was 32
      mm (16-65 mm), median time of the procedure was 44 minutes (8-140 min). The
      corresponding results for noncecal lesions were 97.3%, 95.5%, 0.4%, 2.7%, 30 mm
      (10-109 mm), and 37 min (7-225 min). No significant differences were observed and
      the good treatment results were seen. When the outcomes were analyzed for cecal
      sites considered to be particularly challenging; proximity to appendiceal
      orifice, the ileocecal valve, and the bottom of cecum, the treatment results were
      not inferior to other sites. CONCLUSIONS: ESD is safe and effective even for
      cecal lesions considered challenging to treat. ESD is feasible for cecal lesions.

PMID- 29368546
TI  - Inaugural Editorial.

PMID- 29368548
TI  - Dietary omega-6, but not omega-3, polyunsaturated or saturated fatty acids
      increase inflammation in primary lung mesenchymal cells.
AB  - Obesity is an important risk factor for developing severe asthma. Dietary fatty
      acids, which are increased in sera of obese individuals and after high-fat meals,
      activate the innate immune system and induce inflammation. This study
      investigated whether dietary fatty acids directly cause inflammation and/or
      synergize with obesity-induced cytokines in primary human pulmonary fibroblasts
      in vitro. Fibroblasts were challenged with BSA-conjugated fatty acids [omega-6
      polyunsaturated fatty acids (PUFAs) and omega-3 PUFAs or saturated fatty acids
      (SFAs)], with or without TNF-alpha, and release of the proinflammatory cytokines,
      IL-6 and CXCL8, was measured. We found that the omega-6 PUFA arachidonic acid
      (AA), but not omega-3 PUFAs or SFAs, upregulates IL-6 and CXCL8 release. Combined
      AA and TNF-alpha challenge resulted in substantially greater cytokine release
      than either alone, demonstrating synergy. Synergistic upregulation of IL-6, but
      not CXCL8, was mainly mediated via cyclooxygenase (COX). Inhibition of p38 MAPK
      reduced CXCL8 release, induced by AA and TNF-alpha alone, but not in combination.
      Synergistic CXCL8 release, following AA and TNF-alpha challenge, was not
      medicated via a single signaling pathway (MEK1, JNK, phosphoinositide 3-kinase,
      and NF-kappaB) nor by hyperactivation of NF-kappaB or p38. To investigate if
      these findings occur in other airway cells, effects of AA in primary human airway
      smooth muscle (ASM) cells and human bronchial epithelial cells were also
      investigated. We found proinflammatory effects in ASM cells but not epithelial
      cells. This study suggests that diets rich in omega-6 PUFAs might promote airway
      inflammation via multiple pathways, including COX-dependent and -independent
      pathways, and in an obese person, may lead to more severe airway inflammation.

PMID- 29368547
TI  - Blocking CXCL1-dependent neutrophil recruitment prevents immune damage and
      reduces pulmonary bacterial infection after inhalation injury.
AB  - Smoke inhalation associated with structural fires, wildfires, or explosions leads
      to lung injury, for which innovative and clinically relevant animal models are
      needed to develop effective therapeutics. We have previously reported that damage
      associated molecular patterns (DAMPs) and anti-inflammatory cytokines correlate
      with infectious complications in patients diagnosed with inhalational injury. In
      this study, we describe a novel and translational murine model of acute
      inhalational injury characterized by an accumulation of protein and neutrophils
      in the bronchoalveolar space, as well as histological evidence of tissue damage.
      Mice were anesthetized, and a cannula was placed in the trachea and exposed to
      smoldering plywood smoke three times for 2-min intervals in a smoke chamber. Here
      we demonstrate that this model recapitulates clinically relevant phenotypes,
      including early release of double-stranded DNA (dsDNA), IL-10, monocyte
      chemoattractant protein (MCP)-1, and CXCL1 along with neutrophilia early after
      injury, accompanied by subsequent susceptibility to opportunistic infection with
      Pseudomonas aeruginosa. Further investigation of the model, and in turn a
      reanalysis of patient samples, revealed a late release of the DAMP hyaluronic
      acid (HA) from the lung. Using nitric oxide synthase-deficient mice, we found
      that Nos2 was required for increases in IL-10, MCP-1, and HA following injury but
      not release of dsDNA, CXCL1 expression, early neutrophilia, or susceptibility to
      opportunistic infection. Depletion of CXCL1 attenuated early neutrophil
      recruitment, leading to decreased histopathology scores and improved bacterial
      clearance in this model of smoke inhalation. Together, these data highlight the
      potential therapeutic benefit of attenuating neutrophil recruitment in the first
      24 h after injury in patients.

PMID- 29368549
TI  - Instillation of hyaluronan reverses acid instillation injury to the mammalian
      blood gas barrier.
AB  - Acid (HCl) aspiration during anesthesia may lead to acute lung injury. There is
      no effective therapy. We hypothesized that HCl instilled intratracheally in
      C57BL/6 mice results in the formation of low-molecular weight hyaluronan (L-HA),
      which activates RhoA and Rho kinase (ROCK), causing airway hyperresponsiveness
      (AHR) and increased permeability. Furthermore, instillation of high-molecular
      weight hyaluronan (H-HA; Yabro) will reverse lung injury. We instilled HCl in
      C57BL/6 wild-type (WT), myeloperoxidase gene-deficient (MPO-/-) mice, and CD44
      gene-deficient (CD44-/-) mice. WT mice were also instilled intranasally with H-HA
      (Yabro) at 1 and 23 h post-HCl. All measurements were performed at 1, 5, or 24 h
      post-HCl. Instillation of HCl in WT but not in CD44-/- resulted in increased
      inflammation, AHR, lung injury, and L-HA in the bronchoalveolar lavage fluid
      (BALF) 24 h post-HCl; L-HA levels and lung injury were significantly lower in HCl
      instilled MPO-/- mice. Isolated perfused lungs of HCl instilled WT but not of
      CD44-/- mice had elevated values of the filtration coefficient ( Kf). Addition of
      L-HA on the apical surface of human primary bronchial epithelial cell monolayer
      decreased barrier resistance ( RT). H-HA significantly mitigated inflammation,
      AHR, and pulmonary vascular leakage at 24 h after HCl instillation and mitigated
      the increase of Kf and RT, as well as ROCK2 phosphorylation. Increased H- and L
      HA levels were found in the BALF of mechanically ventilated patients but not in
      healthy volunteers. HCl instillation-induced lung injury is mediated by the L-HA
      CD44-RhoA-ROCK2 signaling pathway, and H-HA is a potential novel therapeutic
      agent for acid aspiration-induced lung injury.

PMID- 29368551
TI  - The development of a 'wet leg' pathway for chronic oedema.
AB  - Chronic oedema and leaking lymphorrhoea can be distressing and challenging for
      patients to live with. This article introduces the Chronic Oedema 'Wet Leg'
      Pathway, which became an output from the Lymphoedema Network Wales 'On the Ground
      Education Project' ( Thomas et al, 2017 ). The evidence-based pathway provides
      nurses and therapists with clear guidelines to support prompt, efficient and
      effective management of all patients with chronic oedema and wet legs. This
      article presents the evidence and demonstrates the benefits of timely active
      treatment for all patients with leaking lymphorrhoea, which includes decreasing
      pain and improving mobility and daily activities. Other benefits include reducing
      the risk of cellulitis and the development of chronic wounds. The pathway also
      demonstrates opportunities for the NHS by decreasing both the number of community
      nursing visits and the number of wound dressings used. By actively treating
      symptoms-rather than simply mopping up the leaking lymphorrhoea-this pathway
      demonstrates value-based health care by reducing waste, harm and variation within
      the NHS.

PMID- 29368550
TI  - Aurothioglucose does not improve alveolarization or elicit sustained Nrf2
      activation in C57BL/6 models of bronchopulmonary dysplasia.
AB  - We previously showed that the thioredoxin reductase-1 (TrxR1) inhibitor
      aurothioglucose (ATG) improves alveolarization in hyperoxia-exposed newborn
      C3H/HeN mice. Our data supported a mechanism by which the protective effects of
      ATG are mediated via sustained nuclear factor E2-related factor 2 (Nrf2)
      activation in hyperoxia-exposed C3H/HeN mice 72 h after ATG administration. Given
      that inbred mouse strains have differential sensitivity and endogenous Nrf2
      activation by hyperoxia, the present studies utilized two C57BL/6 exposure models
      to evaluate the effects of ATG on lung development and Nrf2 activation. The first
      model (0-14 days) was used in our C3H/HeN studies and the 2nd model (4-14 days)
      is well characterized in C57BL/6 mice. ATG significantly inhibited lung TrxR1
      activity in both models; however, there was no effect on parameters of
      alveolarization in C57BL/6 mice. In sharp contrast to C3H/HeN mice, there was no
      effect of ATG on pulmonary NADPH quinone oxidoreductase-1 ( Nqo1) and heme
      oxygenase-1 ( Hmox1) at 72 h in either C57BL/6 model. In conclusion, although ATG
      inhibited TrxR1 activity in the lungs of newborn C57BL/6 mice, effects on lung
      development and sustained Nrf2-dependent pulmonary responses were blunted. These
      findings also highlight the importance of strain-dependent hyperoxic sensitivity
      in evaluation of potential novel therapies.

PMID- 29368552
TI  - Politics and palliative care: Gabon.
AB  - Dion Smyth's review of palliative nursing on the internet.

PMID- 29368553
TI  - Examining self-care, self-compassion and compassion for others: a cross-sectional
      survey of palliative care nurses and doctors.
AB  - : This study examined levels of, and relationships between, self-care ability,
      self-compassion, and compassion among palliative care nurses and doctors.
      METHODS: A total of 369 participants across Australia completed a cross-sectional
      survey comprising a demographic questionnaire and outcome measures for each
      variable. Descriptive and inferential statistics were analysed, controlling for
      potential social-desirability bias. RESULTS: Levels of compassion, self
      compassion and self-care ability varied, with some individuals scoring high or
      low in each. Self-compassion and self-care ability were positively correlated (r
      = .412, p<.001), whereas a negative correlation was observed between compassion
      and self-compassion (r = -.122, p<.05). Linear regression further indicated that:
      increased compassion was associated with a decrease in self-compassion, and
      increased self-care ability was associated with an increase in self-compassion.
      CONCLUSION: These results suggest important implications for self-care in the
      palliative care workforce. Moreover, this study contributes an empirical basis to
      inform future research and education to promote balanced compassion and
      compassion literacy in palliative care practice.

PMID- 29368554
TI  - Politics and palliative nursing.

PMID- 29368555
TI  - Research roundup.
AB  - Synopses of a selection of recently published research articles of relevance to
      palliative care.

PMID- 29368556
TI  - Complex contradictions in conceptualisations of 'dignity' in palliative care.
AB  - BACKGROUND: Internationally, increasing attention is being paid to understanding
      patient experiences of health care. Within palliative care, the Views of Informal
      Carers - Evaluation of Services (VOICES) questionnaire is commonly used for this
      purpose. Among its objectives is to ask family members if their relatives were
      treated with dignity at the end of life. This is regarded as useful for
      understanding the quality of the health care received. AIM: To highlight the
      differences between family members' reports of dignity in the care provided to
      their relatives at the end of life, as reported in the VOICES questionnaire, and
      their narratives about the care their relatives received. METHODS: A total of 21
      cognitive interviews were conducted during a New Zealand pilot of the VOICES
      questionnaire. RESULTS: Discrepancies between ratings of dignity and the lived
      experience of care suggest that lay understandings of dignity may not be
      congruent with that of health care providers. CONCLUSIONS: Bereaved family
      members' self-reports of dignity in end-of-life care captured using survey
      methods alone are inadequate to understand the complex ways in which individuals
      conceptualise and experience dignity within a health care context. The authors
      advocate consideration of multiple, complementary approaches to gathering
      consumer experiences of end-of-life care, as well as research which enables
      service users to interrogate what dignity in care means in an end-of-life
      context.

PMID- 29368557
TI  - Patient perceptions of specialised hospital-based palliative home care: a
      qualitative study using a phenomenographical approach.
AB  - BACKGROUND: Specialised palliative care is given around the clock to palliative
      patients who have severe symptoms or special needs. AIM: The aim of this study
      was to describe patients' perceptions of what it is like to be cared for by a
      specialised palliative care team within hospital-based palliative home care
      (HPHC). METHOD: A qualitative method with semi-structured interviews was used.
      Fourteen patients enrolled in HPHC at a unit for specialised palliative care
      linked to the hospital in the southeast of Sweden participated. The analysis was
      performed with a phenomenographical approach. RESULTS: Four description
      categories were identified: 'it is safe to receive care at home,' 'support and
      commitment', 'having access to a multiprofessional team', and 'how HPHC changes
      everyday life'. To be cared for by HPHC was perceived as safe, and the patients
      thought that having access to competent staff who supported them around the clock
      had improved their care and daily life. CONCLUSION: The need for specialised
      palliative care will likely grow with an ageing population and this form of care
      was perceived as functioning well.

PMID- 29368559
TI  - BJN Award Runner up 2017: Continence Nurse of the Year.
AB  - Continence Promotion Service Team, Liverpool Community Health NHS Trust.

PMID- 29368560
TI  - A unique perspective.

PMID- 29368558
TI  - Clinical nurses' attitudes towards death and caring for dying patients in China.
AB  - OBJECTIVE: To examine Chinese clinical nurses' attitudes towards death and caring
      for dying patients, and to examine the relationships between clinical nurses'
      attitudes towards death and caring for dying patients. METHODS: A convenience
      sample of 770 clinical nurses from 15 hospitals in China. All participants
      completed the Chinese version of the Frommelt Attitude Toward Care of the Dying
      Scale, Form B (FATCOD-B-C), the Chinese version of the Death Attitude Profile
      Revised (DAP-R-C), and a demographic questionnaire. RESULTS: The mean score of
      the FATCOD-B-C items was 95.62 (SD = 7.45). The majority of Chinese clinical
      nurses were likely to provide care for the dying person's family (mean = 3.77),
      but did not have a positive attitude towards communication with the dying
      person(mean = 2.62). The majority of Chinese clinical nurses showed low scores on
      death avoidance (mean=1.96) and natural acceptance (mean = 1.61), and most of
      them viewed death as a passageway to a happy afterlife (mean = 4.33). Attitudes
      towards caring for dying patients were significantly negatively correlated with
      fear of death (r = -0.120) and positively correlated with approach acceptance (r
      = 0.127) and natural acceptance (r = 0.117). Factors that predicted clinical
      nurses' attitudes towards the care of dying patients included education level,
      fear of death, approach acceptance, religious beliefs, previous education on
      death and dying, natural acceptance, professional title, and experience with
      death or dying patients, which accounted for 18.7% of the variance. CONCLUSION:
      Nurses' personal attitudes towards death were associated with their attitudes
      towards the care of dying patients. Training and educational programmes for
      clinical nurses should take into consideration nurses' personal attitudes towards
      death as well as their cultural backgrounds and religious beliefs.

PMID- 29368561
TI  - Source isolation and patient wellbeing in healthcare settings.
AB  - Multi-resistant bacteria pose an increasing and significant challenge to public
      health. Isolation precautions in patients with multi-drug-resistant bacteria and
      other communicable infectious agents can be associated with adverse effects.
      Although few would dispute the need for such practices in preventing the spread
      of transmissible infections, patients' perspectives of isolation suggest that the
      imposed environment creates barriers to their physical, social and emotional
      needs. This article reviews the literature to uncover any reliable evidence
      supporting the assertion that the experience of isolation in healthcare settings
      impacts adversely on patient wellbeing. Database searches identified 25 relevant
      papers published between 1990 and 2017. A number of studies claimed to have
      uncovered an association between negative patient experiences and isolation.

PMID- 29368562
TI  - What's your proof?

PMID- 29368563
TI  - Preventing skin damage and incontinence-associated dermatitis in older people.

PMID- 29368564
TI  - A call to action to improve the visibility of research by nursing, midwifery and
      care staff.

PMID- 29368565
TI  - Developing a digital learning version of a mentorship training programme.
AB  - This article describes the experience of one university team in developing,
      delivering and evaluating an online Nursing and Midwifery Council-approved
      mentorship programme for nurses and midwives who support pre-registration
      students in practice. Although the authors are confident of the quality of the
      educational provision, this article does not discuss this programme as an
      exemplar of best practice, but aims to share the learning gained from the
      experience of introducing a digital learning version of a mentorship course.

PMID- 29368566
TI  - Ward staff perceptions of the role of the advanced nurse practitioner in a
      'hospital at day' setting.
AB  - AIM: to examine ward staff perceptions on the role of the 'hospital at day'
      advanced nurse practitioner (ANP). This term is used locally to refer to a model
      first introduced into 'hospital at night' teams, in response to changes in
      working patterns of junior doctors, where an advanced nurse practitioner is based
      on the ward-the model was subsequently rolled out to daytime teams. METHODS: a
      qualitative descriptive phenomenological approach was adopted to carry out this
      study with a purposive sample of ten participants. Participants were interviewed
      individually using semi-structured interviews to gain insights into their
      perceptions on the role of the ANP, following Colaizzi's analytical model of data
      analysis. FINDINGS: four major themes were identified. The first overarching
      theme was effectiveness of the ANP role. There was evidence that the role was not
      only clinically effective in the ward but also in relation to organisational
      priorities such as impact on patient flow. Secondly it was acknowledged that
      having an ANP based on the ward and as a 'constant' in the ward area, when
      medical teams rotate, provides team stability and improves the functioning of the
      ward area. Despite the positivity recognised, the third theme identified that
      having a ward-based ANP may affect skill acquisition and development and may lead
      to the 'de-skilling' of staff. Lastly it was acknowledged that there remains an
      overall confusion about the role of the ANP. CONCLUSION: the themes identified
      reflect what is already known about the wider perceived role of the ANP.
      Moreover, this study adds to the limited literature available specifically on the
      benefits of the ANP within 'hospital at day' roles.

PMID- 29368567
TI  - Transgender prisoners.

PMID- 29368568
TI  - Will the introduction of an 'opt-out' system increase organ donations?
AB  - Emeritus Professor Alan Glasper, University of Southampton, discusses the
      government initiative to improve the rates of organ donation by members of the
      public.

PMID- 29368570
TI  - Royal College of Nursing's Standards for Infusion Therapy: an overview.

PMID- 29368569
TI  - Managing the costs of clinical negligence within hospital trusts.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses the House of Commons Committee of Public Accounts Report on
      the escalating costs of clinical negligence in hospital trusts.

PMID- 29368571
TI  - Communicating effectively with a person living with dementia.

PMID- 29368572
TI  - Managing dysfunctional central venous access devices: a practical approach to
      urokinase thrombolysis.
AB  - Tunnelled central venous access devices (CVADs) are defined as any intravenous
      multipurpose catheters placed within the central veins for use in haemodialysis
      and administration of blood products or chemotherapy in oncology and
      haematological conditions. Frequent complications include thrombosis and catheter
      related infection, which may lead to significant adverse patient outcomes. Once
      thrombosis is suspected correction should be attempted empirically with
      thrombolytic agents. Commonly available thrombolytic agents in the UK include
      urokinase (Syner-Kinase) and alteplase (Cathflo). It is well recognised that
      urokinase usage differs widely and concerns were raised by clinicians about the
      variation of dose regimens nationally. The objective of the CVAD Focus Group was
      to address this issue and offer guidance in the management of suspected
      thrombosis of CVAD with urokinase using two algorithms for renal and non-renal
      dysfunctional CVAD and to audit prospectively the outcomes of intervention.

PMID- 29368574
TI  - Making all routes into nursing attractive.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, discusses recent
      developments in technical qualifications and how to encourage more young people
      to consider a career in nursing.

PMID- 29368573
TI  - The risk of microbial contamination associated with six different needle-free
      connectors.
AB  - BACKGROUND: needle-free connectors are widely used in clinical practice. The aim
      of this study was to identify any differences between microbial ingress into six
      different connectors (three neutral-displacement, one negative-displacement and
      two anti-reflux connectors). METHODS: each connector underwent a 7-day clinical
      simulation involving repeated microbial contamination of the connector's
      injection ports with Staphylococcus aureus followed by decontamination and then
      saline flushes through each connector. The simulation was designed to be a
      surrogate marker for the potential risk of contamination in clinical practice.
      RESULTS: increasing numbers of S. aureus were detected in the flushes over the 7
      days of sampling despite adherence to a rigorous decontamination programme.
      Significant differences in the number of S. aureus recovered from the saline
      flush of some types of connectors were also detected. Two different durations (5-
      and 15-second) of decontamination of the injection ports with 70% isopropyl
      alcohol (IPA) wipes were also investigated. There was no significant difference
      between the median number of S. aureus recovered in the saline flushes following
      a 5-second (165.5, 95% CI=93-260) or a 15-second decontamination regimen (75, 10
      190). CONCLUSIONS: The findings suggest that there may be differences in the risk
      of internal microbial contamination with different types of connectors and that
      even 15 seconds of decontamination may not fully eradicate microorganisms from
      the injection ports of some devices.

PMID- 29368575
TI  - From staff nurse to nurse consultant: Spiritual care part 10: Shinto.
AB  - John Fowler, Educational Consultant, explores spiritual care for clinically based
      nurses, focusing on patients who follow the Shinto religion.

PMID- 29368576
TI  - Designing and evaluating vascular access training using educational theory.
AB  - Clinical skills learning is commonplace for all health professionals, with many
      training programmes incorporating multiple modes of facilitation, aligned to
      clinical standards and evidence-based research. There is often variance, however,
      in the facilitation of training programmes across healthcare settings and
      disciplines, highlighting differing levels of knowledge and clinical competence
      and illustrating a need for standardisation of training. Evidence illustrates
      many different approaches to learning from the traditional 'see one, do one,
      teach one', to academic facilitation by clinical skills tutors, to in-house
      expert facilitation. There has been a significant change in the medical education
      paradigm towards a more structured work-based competency assessed approach to
      learning. This paper explores the theoretical aspects of clinical skills learning
      and leadership theory in healthcare practice, placing emphasis on
      interprofessional and collaborative working and learning partnerships.

PMID- 29368577
TI  - Current thinking on catheter securement and infection prevention.
AB  - Janice Gabriel, Clinical Network Manager, NHS England (Wessex), Southampton,
      janice.gabriel@nhs.net , explains the importance of catheter securement in
      preventing complications of infusion therapy.

PMID- 29368578
TI  - Human rights and political crisis in Brazil: Public health impacts and
      challenges.
AB  - : In 31 August 2016, Brazilian president Dilma Rousseff was impeached and
      replaced by her vice president Michel Temer. Herein, we examine how the
      conservative agenda of Mr Temer and his supporters is influencing key decisions
      in the human rights and public health arena in Brazil. The government's austerity
      agenda includes severe cuts in critical areas such as health, education and
      science, jeopardising well-known strategies such as the Brazilian Public Health
      System (SUS) and nationwide cash transfer program, 'Bolsa Familia' - both
      benefited millions and were the largest of their kind in the world. Mr Temer's
      decisions show not only severe cuts in critical areas but also a political agenda
      that clearly demonstrates a broad shift away from the progressivism and social
      agenda presented and supported by its predecessors. Most vulnerable groups such
      as the LGBTQ community, women, people who use drugs and disenfranchised
      communities have been severely affected. Mr Temer's administration is putting
      Brazil far from its once nationwide goal to foster free and universal health care
      access and social equity for all its citizens. The near future for Brazil is
      unknown, but both national and international communities anticipate severe
      problems within the national human rights arena, if nothing changes.
      ABBREVIATIONS: CCT: Conditional Cash Transfer; LGBTQ: Lesbian, Gay, Bisexual,
      Transgender and Queer (and/or Questioning); SUS: Brazilian Public Health System.

PMID- 29368579
TI  - Male circumcision for HIV prevention: Awareness, risk compensation, and risk
      perceptions among South African women.
AB  - Medical male circumcision (MMC) is a proven method of HIV risk reduction for men
      in southern Africa. MMC promotion campaigns and scale-up programmes are widely
      implemented throughout the Republic of South Africa. However, the impact of
      promoting MMC on women's awareness, beliefs, and behaviours has been
      understudied. We conducted a self-administered anonymous survey of 279 women
      receiving health services in an impoverished township located in Cape Town, South
      Africa. Results showed that two in three women were unaware that male
      circumcision partially protects men from contracting HIV. Women who were aware of
      MMC for HIV prevention also endorsed beliefs that male circumcision reduces the
      need for men to worry about HIV and reduces the need for men to use condoms. Male
      circumcision awareness was also related to reduced perceptions of HIV risk among
      women. Multivariable models showed that women's MMC awareness, circumcision risk
      compensation beliefs, and risk perceptions were associated with decreased condom
      use and higher HIV risk index scores defined as number of condomless vaginal
      intercourse X number of sex partners. These results suggest a need for MMC
      education efforts tailored for women living in communities with high-HIV
      prevalence where men are targeted for MMC.

PMID- 29368580
TI  - Patient characteristics and the therapist as predictors of depressed patients'
      outcome expectation over time: A multilevel analysis.
AB  - OBJECTIVE: Although there is an established link between patients' early positive
      outcome expectation for and their actual improvement from therapy, there is
      little research on patients' change in outcome expectation across therapy and
      both patient and therapist correlates of early outcome expectation level and
      change. The present study examined: (i) the overall trajectory of change in
      patients' outcome expectation through cognitive-behavioral therapy (CBT) for
      depression; (ii) patient characteristics as predictors of both initial outcome
      expectation and change in outcome expectation; and (iii) between-therapist
      effects in outcome expectation change. METHOD: Depressed patients (N = 143)
      received a brief course of CBT. Outcome expectation was measured at screening,
      pretreatment, session 7, and session 14. RESULTS: Outcome expectation linearly
      increased from screening to session 14. When controlling for other patient
      characteristics at intake, having previous depressive episodes was negatively
      associated with initial outcome expectation and higher well-being was positively
      associated with initial outcome expectation. When controlling for early alliance
      and early symptom change, outcome expectation change was predicted by previous
      depressive episodes. Finally, therapist effects emerged in outcome expectation
      over time. CONCLUSIONS: Various depressed patients' characteristics predict
      initial outcome expectation level and change, with significant between
      therapists' differences related to outcome expectation change. Clinical or
      methodological significance of this article: The present study contributed much
      needed information on the pattern of change in outcome expectations, as well as
      on correlates of both early outcome expectation and outcome expectancy growth
      (for which almost no prior data exist). Having this information, clinicians may
      respond more appropriately to low or decreasing levels of outcome expectation and
      capitalize on its changeability. Moreover, the study revealed a therapist effect
      on outcome expectation, which pushes the field to a vital next wave of process
      outcome research-i.e., moving beyond total correlations to parsing between
      patient and between-therapist variability in clinical constructs and construct
      outcome associations.

PMID- 29368581
TI  - Purple urine bag syndrome: a truly harmless sign?
AB  - Purple urine bag syndrome is an uncommon condition that describes the purple
      discolouration of a catheter bag and tubing. It mainly affects patients with
      limited mobility who have long-term catheters. Although benign in nature per se,
      its presence can alarm both patient and practitioner unfamiliar with the
      syndrome. Here, we describe two cases of asymptomatic patients who both presented
      to outpatient clinic with the characteristic purple discolouration of their long
      term catheters and tubing. The report discusses the pathophysiology of the
      syndrome and initial investigation and management. Although the syndrome is
      considered benign, it may signify occult urine tract infection. This should not
      be ignored even if the patient is asymptomatic, given the likely co-morbidities
      of the patients affected. Healthcare professionals - particularly urologists and
      geriatricians - need to be aware of this unusual syndrome so as to initiate
      appropriate investigation and possible treatment as soon as possible.

PMID- 29368582
TI  - Mineralized Biomaterials Mediated Repair of Bone Defects Through Endogenous
      Cells.
AB  - Synthetic biomaterials that create a dynamic calcium (Ca2+)-, phosphate (PO43-)
      ion-, and calcium phosphate (CaP)-rich microenvironment, similar to that found in
      native bone tissue, have been shown to promote osteogenic commitment of stem
      cells in vitro and in vivo. The intrinsic osteoconductivity and osteoinductivity
      of such biomaterials make them promising bone grafts for the treatment of bone
      defects. We thus aimed to evaluate the potential of mineralized biomaterials to
      induce bone repair of a critical-sized cranial defect in the absence of exogenous
      cells and growth factors. Our results demonstrate that the mineralized
      biomaterial alone can support complete bone formation within critical-sized bone
      defects through recruitment of endogenous cells and neo-bone tissue formation in
      mice. The newly formed bone tissue recapitulated many key characteristics of
      native bone such as formation of bone minerals reaching similar bone mineral
      density, presence of bone-forming osteoblasts and tartrate-resistant acid
      phosphatase-expressing osteoclasts, as well as vascular networks. Biomaterials
      that recruit endogenous cells and provide a tissue-specific microenvironment to
      modulate cellular behavior and support generation of functional tissues are a key
      step forward in moving bench-side tissue engineering approaches to the bedside.
      Such tissue engineering strategies could eventually pave the path toward readily
      available therapies that significantly reduce patient cost of care and improve
      overall clinical outcomes.

PMID- 29368583
TI  - Determination of quinolone residues in raw cow milk. Application of polar stir
      bars and ultra-high performance liquid chromatography-tandem mass spectrometry.
AB  - Seventeen quinolone antibiotics were determined in cows' milk. A method of high
      sensitivity, selectivity and accuracy was developed. Accuracy (trueness and
      precision), linearity, sensitivity, selectivity, decision limit and detection
      capability were established following the recommendations of the Commission
      Decision 2002/657/EC and the Food and Drug Administration (FDA) guideline. The
      use of polar stir-bar sorptive extraction (SBSE) prior to UHPLC-MS/MS analysis is
      proposed. The variables that affect SBSE were optimised using multivariate
      optimisation strategies. The ionic strength, the extraction time and the sample
      volume were studied. pH and stir-bar coating (polydimethylsiloxane, PDMS, and
      polyethyleneglycol modified silicone, PEG) were studied. PEG showed the best
      extraction yield at pH 6. For validation, a matrix-matched calibration and a
      recovery assay were carried out. Limits of quantification from 0.5 MUg kg-1 for
      nalidixic acid, flumequine and piromidic acid, to 4.0 MUg kg-1 for sarafloxacin
      were calculated. The precision (%, RSD) was lower than 15% for all antibiotics.
      Recoveries in fortified samples were between 88 and 114%.

PMID- 29368585
TI  - The Mini-International Neuropsychiatric Interview is useful and well accepted as
      part of the clinical assessment for depression and anxiety in primary care: a
      mixed-methods study.
AB  - BACKGROUND: Psychiatric complaints are common among primary care patients, with
      depression and anxiety being the most frequent. Diagnosis of anxiety and
      depression can be difficult, potentially leading to over- as well as under
      diagnosis. The diagnostic process can be facilitated by incorporating structured
      interviews as part of the assessment. One such instrument, the Mini-International
      Neuropsychiatric Interview (MINI), has been established and accepted in
      psychiatric care. The purpose of this study was to explore the experiences and
      perceptions of the paper-and-pen version of MINI version 6.0 among patients and
      staff in primary care centers in Sweden. METHODS: The MINI was introduced at
      three primary care centers and was conducted by either therapists or general
      practitioners. Patients presented with symptoms that could suggest depression or
      anxiety disorders. The duration of the interview was recorded. The experiences
      and perceptions of 125 patients and their interviewers were collected using a
      structured questionnaire. Global satisfaction was measured with a visual-analog
      scale (0-100). Semi-structured interviews were conducted with 24 patients and
      three therapists, and focus groups were held with 17 general practitioners.
      Qualitative content analysis was used for the interviews and focus groups. The
      findings across the groups were triangulated with results from the
      questionnaires. RESULTS: The median global satisfaction with the MINI was 80 for
      patients and 86 for interviewers. General practitioners appreciated that the MINI
      identified comorbidities, as one-third of the patients had at least two
      psychiatric diagnoses. The MINI helped general practitioners attain a more
      accurate diagnosis. Patients appreciated that the MINI helped them recognize and
      verbalize their problems and did not find it intrusive. Patients and interviewers
      had mixed experiences with the yes-no format of the MINI, and the risk of
      subjective interpretations was acknowledged. Patients, general practitioners and
      therapists stated that the MINI contributed to appropriate treatment. The MINI
      assessment lasted 26 min on average (range 12 to 60 min). CONCLUSIONS: The paper
      and-pen version of the MINI could be useful in primary care as part of the
      clinical assessment of patients with problems suggestive of depression or anxiety
      disorders. The MINI was well accepted by patients, general practitioners and
      therapists.

PMID- 29368586
TI  - Building flexibility and managing complexity in community mental health: lessons
      learned in a large urban centre.
AB  - BACKGROUND: Across many jurisdictions, adults with complex mental health and
      social needs face challenges accessing appropriate supports due to system
      fragmentation and strict eligibility criteria of existing services. To support
      this underserviced population, Toronto's local health authority launched two
      novel community mental health models in 2014, inspired by Flexible Assertive
      Community Team principles. This study explores service user and provider
      perspectives on the acceptability of these services, and lessons learned during
      early implementation. METHODS: We purposively sampled 49 stakeholders (staff,
      physicians, service users, health systems stakeholders) and conducted 17 semi
      structured qualitative interviews and 5 focus groups between October 23, 2014 and
      March 2, 2015, exploring stakeholder perspectives on the newly launched team
      based models, as well as activities and strategies employed to support early
      implementation. Interviews and focus groups were audio recorded, transcribed
      verbatim and analyzed using thematic analysis. RESULTS: Findings revealed wide
      ranging endorsement for the two team-based models' success in engaging the target
      population of adults with complex service needs. Implementation strengths
      included the broad recognition of existing service gaps, the use of
      interdisciplinary teams and experienced service providers, broad partnerships and
      collaboration among various service sectors, training and team building
      activities. Emerging challenges included lack of complementary support services
      such as suitable housing, organizational contexts reluctant to embrace change and
      risk associated with complexity, as well as limited service provider and
      organizational capacity to deliver evidence-based interventions. CONCLUSIONS:
      Findings identified implementation drivers at the practitioner, program, and
      system levels, specific to the implementation of community mental health
      interventions for adults with complex health and social needs. These can inform
      future efforts to address the health and support needs of this vulnerable
      population.

PMID- 29368587
TI  - Widespread signatures of selection for secreted peptidases in a fungal plant
      pathogen.
AB  - BACKGROUND: Fungal plant pathogens secrete a large arsenal of hydrolytic enzymes
      during the course of infection, including peptidases. Secreted peptidases have
      been extensively studied for their role as effectors. In this study, we combined
      transcriptomics, comparative genomics and evolutionary analyses to investigate
      all 39 secreted peptidases in the fungal wheat pathogen Zymoseptoria tritici and
      its close relatives Z. pseudotritici and Z. ardabiliae. RESULTS: RNA-seq data
      revealed that a majority of the secreted peptidases displayed differential
      transcription during the course of Z. tritici infection, indicative of
      specialization for different stages in the life cycle. Evolutionary analyses
      detected widespread evidence of adaptive evolution acting on at least 28 of the
      peptidases. A few peptidases displayed lineage-specific rates of molecular
      evolution, suggesting altered selection pressure in Z. tritici following host
      specialization on domesticated wheat. The peptidases belonging to MEROPS families
      A1 and G1 emerged as a particularly interesting group that may play key roles in
      host-pathogen co-evolution, host adaptation and pathogenicity. Sister genes in
      the A1 and G1 families showed accelerated substitution rates after gene
      duplications. CONCLUSIONS: These results suggest widespread evolution of secreted
      peptidases leading to novel gene functions, consistent with predicted models of
      "escape from adaptive conflict" and "neo-functionalization". Our analyses
      identified candidate genes worthy of functional analyses that may encode effector
      functions, for example by suppressing plant defenses during the biotrophic phase
      of infection.

PMID- 29368588
TI  - Vitamin D in children with growth hormone deficiency due to pituitary stalk
      interruption syndrome.
AB  - BACKGROUND: Recent studies have shown a relationship between vitamin D status and
      growth hormone (GH) and insulin-like growth factor 1 (IGF1). The objective of
      this study was to assess vitamin D status in children with GH deficiency due to
      pituitary stalk interruption syndrome (PSIS) and to investigate the relationship
      between 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25 (OH) 2D)
      serum levels and patient characteristics. METHODS: A retrospective single-center
      study of 25OHD and 1,25(OH)2D serum concentrations in 50 children with PSIS at
      the initial evaluation before treatment. RESULTS: Mean concentrations of 33.2 +/-
      18.0 ng/mL for 25OHD and 74.5 +/- 40.7 ng/L for 1,25(OH)2D were measured.
      Additionally, 25OHD concentrations were significantly higher in boys than in
      girls (p = 0.04) and lower in the cold season than in the sunny season (p =
      0.03). Significant positive correlations were observed between the GH peak and
      serum 1,25 (OH) 2D concentrations (Rho = 0.35; p = 0.015) and the
      1,25(OH)2D/25OHD ratio (Rho = 0.29; p < 0.05). No correlation was found for other
      characteristics, including IGF1. CONCLUSIONS: Vitamin D status in children with
      hypothalamic-pituitary deficiency due to PSIS was similar to that reported in
      national and European studies in healthy children. The positive significant
      correlations between the GH peak and the 1,25 (OH)2D concentration as well as
      with the 1,25 (OH)2D/25OHD ratio suggest that even in these patients who had
      severely impaired GH secretion and low IGF1 levels, an interplay between the
      GH/IGF1 axis and the vitamin D system still exists.

PMID- 29368589
TI  - Expanded carrier screening and preimplantation genetic diagnosis in a couple who
      delivered a baby affected with congenital factor VII deficiency.
AB  - BACKGROUND: Preimplantation genetic diagnosis (PGD) is a powerful tool for
      preventing the transmission of Mendelian disorders from generation to generation.
      However, PGD only can identify monogenically inherited diseases, but not other
      potential monogenic pathologies. We aimed to use PGD to deliver a healthy baby
      without congenital FVII deficiency or other common Mendelian diseases in a couple
      in which both individuals carried a deleterious mutation in the F7 gene. METHODS:
      After both members of the couple were confirmed to be carriers of the F7 gene
      mutation by Sanger sequencing, expanded carrier screening (ECS) for 623 recessive
      inheritance diseases was performed to detect pathological mutations in other
      genes. PGD and preimplantational genetic screening (PGS) were employed to exclude
      monogenic disorders and aneuploidy for their embryos. RESULTS: ECS using targeted
      capture sequencing technology revealed that the couple carried the heterozygous
      disease-causative mutations c.3659C > T (p.Thr1220Ile) and c.3209G > A
      (p.Arg1070Gln) in the CFTR gene. After PGD and PGS, one of their embryos that was
      free of congenital FVII deficiency, cystic fibrosis (CF) and aneuploidy was
      transferred, resulting in the birth of a healthy 3200 g male infant. CONCLUSION:
      We successfully implemented PGD for congenital FVII deficiency and PGD after ECS
      to exclude CF for the first time to the best of our knowledge. Our work
      significantly improved the reproductive outcome for the couple and provides a
      clear example of the use of ECS combined with PGD to avoid the delivery of
      offspring affected not only by identified monogenically inherited diseases but
      also by other potential monogenic pathologies and aneuploidy.

PMID- 29368591
TI  - RNA gene profile variation in peripheral blood mononuclear cells from rhesus
      macaques immunized with Hib conjugate vaccine, Hib capsular polysaccharide and TT
      carrier protein.
AB  - BACKGROUND: The Haemophilus influenzae type b (Hib) conjugate vaccine has been
      widely used in children to prevent invasive Hib disease because of its strong
      immunogenicity and antibody response induction relative to the capsular
      polysaccharide (CPS) antigen. The data from vaccine studies suggest that the
      conjugate vaccine contains carrier proteins that enhance and/or regulate the
      antigen's immunogenicity, but the mechanism of this enhancement remains unclear.
      METHODS: To explore the immunological role of the conjugate vaccine, we compared
      the immune responses and gene profiles of rhesus macaques after immunization with
      CPS, carrier protein tetanus toxoid (TT) or conjugate vaccine. RESULTS: A
      distinct immune response was induced by the Hib conjugate vaccine but not by CPS
      or carrier protein TT. The genes that were dynamically regulated in conjunction
      with the macaque immune responses to the conjugate vaccine were investigated.
      CONCLUSIONS: We propose that these genes are involved in the induction of
      specific immunity that is characterized by the appearance and maintenance of
      antibodies against Hib.

PMID- 29368590
TI  - Identification of AUXIN RESPONSE FACTOR gene family from Prunus sibirica and its
      expression analysis during mesocarp and kernel development.
AB  - BACKGROUND: Auxin response factors (ARFs) in auxin signaling pathway are an
      important component that can regulate the transcription of auxin-responsive genes
      involved in almost all aspects of plant growth and development. To our knowledge,
      the comprehensive and systematic characterization of ARF genes has never been
      reported in Prunus sibirica, a novel woody biodiesel feedstock in China. RESULTS:
      In this study, we identified 14 PsARF genes with a perfect open reading frame
      (ORF) in P. sibirica by using its previous transcriptomic data. Conserved motif
      analysis showed that all identified PsARF proteins had typical DNA-binding and
      ARF domain, but 5 members (PsARF3, 8 10, 16 and 17) lacked the dimerization
      domain. Phylogenetic analysis of the ARF proteins generated from various plant
      species indicated that ARFs could be categorized into 4 major groups (Class I,
      II, III and IV), in which all identified ARFs from P. sibirica showed a closest
      relationship with those from P. mume. Comparison of the expression profiles of 14
      PsARF genes in different developmental stages of Siberian apricot mesocarp (SAM)
      and kernel (SAK) reflected distinct temporal or spatial expression patterns for
      PsARF genes. Additionally, based on the expressed data from fruit and seed
      development of multiple plant species, we identified 1514 ARF-correlated genes
      using weighted gene co-expression network analysis (WGCNA). And the major portion
      of ARF-correlated gene was characterized to be involved in protein, nucleic acid
      and carbohydrate metabolic, transport and regulatory processes. CONCLUSIONS: In
      summary, we systematically and comprehensively analyzed the structure, expression
      pattern and co-expression network of ARF gene family in P. sibirica. All our
      findings provide theoretical foundation for the PsARF gene family and will pave
      the way for elucidating the precise role of PsARF genes in SAM and SAK
      development.

PMID- 29368592
TI  - Genome-wide protein phylogenies for four African cichlid species.
AB  - BACKGROUND: The thousands of species of closely related cichlid fishes in the
      great lakes of East Africa are a powerful model for understanding speciation and
      the genetic basis of trait variation. Recently, the genomes of five species of
      African cichlids representing five distinct lineages were sequenced and used to
      predict protein products at a genome-wide level. Here we characterize the
      evolutionary relationship of each cichlid protein to previously sequenced animal
      species. RESULTS: We used the Treefam database, a set of preexisting protein
      phylogenies built using 109 previously sequenced genomes, to identify Treefam
      families for each protein annotated from four cichlid species: Metriaclima zebra,
      Astatotilapia burtoni, Pundamilia nyererei and Neolamporologus brichardi. For
      each of these Treefam families, we built new protein phylogenies containing each
      of the cichlid protein hits. Using these new phylogenies we identified the
      evolutionary relationship of each cichlid protein to its nearest human and
      zebrafish protein. This data is available either through download or through a
      webserver we have implemented. CONCLUSION: These phylogenies will be useful for
      any cichlid researchers trying to predict biological and protein function for a
      given cichlid gene, understanding the evolutionary history of a given cichlid
      gene, identifying recently duplicated cichlid genes, or performing genome-wide
      analysis in cichlids that relies on using databases generated from other species.

PMID- 29368593
TI  - Better clinical outcome with direct oral anticoagulants in hospitalized heart
      failure patients with atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure and
      is associated with higher mortality. Although previous studies have reported that
      direct oral anticoagulants (DOACs) reduce the risk of cardiovascular events in
      out-patients with AF, it remains unclear whether DOACs reduce mortality in
      hospitalized heart failure (HHF) patients with AF. Therefore, we examined the
      impact of DOACs on mortality in this group of patients. METHODS: Consecutive 497
      HHF patients with AF were retrospectively registered and divided into three
      groups on the basis of the presence of anticoagulant therapy: non-anticoagulant
      group (Non, n = 90), Vit K antagonists (VKAs) group (n = 257) and DOACs group (n
      = 150). We followed up all the patients for mortality. RESULTS: In the Kaplan
      Meier analysis (mean follow-up of 1093 days), all-cause mortality was
      significantly lower in the VKAs and DOACs groups than in the Non group (31.1% and
      15.3% vs. 43.3%, log-rank P < 0.001). In the multivariable Cox proportional
      hazard analysis after adjusting for other potential confounding factors, usage of
      DOACs and VKAs were independently associated with lower mortality in HHF patients
      AF (DOACs, HR 0.356, P = 0.001; VKAs, HR 0.472, P = 0.002). Furthermore, the
      propensity-matched 1:1 cohort was assessed based on the propensity score (DOACs,
      n = 114 and VKAs, n = 114). All-cause mortality was significantly lower in the
      DOACs group than in the VKAs group in the post-matched cohort (12.3% vs. 35.1%,
      log-rank P = 0.038). In the Cox proportional hazard analysis, the use of DOACs
      was associated with lower mortality in the post-matched cohort (HR 0.526, P =
      0.041). CONCLUSION: Appropriate use of anticoagulants in HHF patients with AF is
      important, and DOACs potentially improve all-cause mortality in such patients.

PMID- 29368594
TI  - Comparison of a loading dose of dexmedetomidine combined with propofol or
      sevoflurane for hemodynamic changes during anesthesia maintenance: a prospective,
      randomized, double-blind, controlled clinical trial.
AB  - BACKGROUND: There may be great individual variability in the hemodynamic effects
      of this dexmedetomidine. For this reason, the dose must be carefully adjusted to
      achieve the desired clinical effect. Whether a loading dose of dexmedetomidine
      produces hemodynamic side effects during the anesthesia maintenance is unknown.
      The aim of this study was to compare the effects of a loading dose of
      dexmedetomidine combined with propofol or sevoflurane on hemodynamics during
      anesthesia maintenance. METHODS: Eighty-four patients who were scheduled for
      general surgery under balanced general anesthesia were randomly allocated into 4
      groups (n = 21): the propofol and dexmedetomidine group, the sevoflurane and
      dexmedetomidine group, the propofol and normal saline group, or the sevoflurane
      and normal saline group. The hemodynamic indexes at the time of just before, 5
      min after and the end of study drug infusion (dexmedetomidine or normal saline)
      were recorded. The incidence rates of increasing blood pressure at the end of
      study drug infusion (greater than 20% compared to baseline or before study drug
      infusion) were evaluated. RESULTS: Mean arterial pressure increased significantly
      (P < 0.01) only in the propofol and dexmedetomidine group after intravenous
      dexmedetomidine compared administration. 80% of cases with propofol and
      dexmedetomidine had increased mean arterial blood pressure compared to only 5% of
      cases in the sevoflurane and dexmedetomidine group (P < 0.05). Heart rates in the
      propofol and dexmedetomidine and the sevoflurane and dexmedetomidine groups
      decreased significantly after dexmedetomidine infusion (P < 0.01). CONCLUSIONS:
      Intraoperative administration of a loading dose of dexmedetomidine combined with
      propofol in anesthesia maintenance proceeded a significant increase in blood
      pressure. In contrast, it combines with sevoflurane didn't produce increased
      blood pressure. Meanwhile it is not unexpected that dexmedetomidine combined with
      propofol or sevofurance decreased heart rate, due to the known side effects of
      DEX. Therefore, dexmedetomidine should be used cautiously during the entire
      intravenous anesthesia maintenance period, especially during maintenance with
      propofol. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IOR
      17010423 , registered on 13 January 2017.

PMID- 29368595
TI  - Short-term effects and safety of an acute increase of intraocular pressure after
      intravitreal bevacizumab injection on corneal endothelial cells.
AB  - BACKGROUND: The purpose of this study is to evaluate short-term effects and
      safety of an acute increase of intraocular pressure (IOP) after single-dose
      intravitreal bevacizumab injection on corneal endothelial cells and central
      corneal thickness. METHODS: Forty-two patients who underwent intravitreal
      injection of 2.5 mg/0.1 ml bevacizumab because of central serous
      chorioretinopathy or diabetic macular edema were included in this study. The
      changes of IOP, corneal endothelial cells, and corneal thickness at baseline, 2
      min, 5 min, and 30 min after injection were analyzed prospectively with a
      specular microscope. RESULTS: In all patients, the mean IOPs at baseline, 2 min,
      5 min, and 30 min after injection were 11.48 +/- 2.22 mmHg, 49.71 +/- 10.73 mmHg,
      37.64 +/- 11.68 mmHg, and 14.88 +/- 4.77 mmHg, respectively. These changes were
      significant (p < 0.01). In only one eye, IOP did not decrease to <=30 mmHg even
      at 30 min after injection. According to changes in IOP with time, the coefficient
      of variation of the corneal endothelium significantly increased (p = 0.03), but
      cell density, hexagonality of the corneal endothelium, and central corneal
      thickness did not change (p = 0.79, 0.21, and 0.08, prospectively). One week
      after injection, there was no sign of inflammation or any other complications in
      all 42 eyes. CONCLUSIONS: After intravitreal injection, IOP rapidly increases,
      then decreases to the normal range in most eyes 30 min after injection and it is
      tolerable to corneal endothelium. TRIAL REGISTRATION: Clinical Research
      Information Service (CRiS), Republic of Korea, KCT0002645 . Retrospectively
      registered 9 January 2018.

PMID- 29368596
TI  - Infant formula feeding practices and the role of advice and support: an
      exploratory qualitative study.
AB  - BACKGROUND: Infant formula feeding practices are an important consideration for
      obesity prevention. An infant's diet is influential on their later risk of
      developing overweight or obesity, yet very little is known about infant formula
      feeding practices. It is plausible that certain modifiable practices may put
      children at higher risk of developing overweight or obesity, for example how much
      and how often a baby is fed. Understanding how parents use infant formula and
      what factors may influence this practice is therefore important. Moreover,
      parents who feed their infants formula have identified a lack of support and
      access to resources to guide them. Therefore this study aimed to explore parents'
      infant formula feeding practices to understand how parents use infant formula and
      what factors may influence this practice. METHODS: Using an explorative
      qualitative design, data were collected using semi-structured telephone
      interviews and analysed using a pragmatic inductive approach to thematic
      analysis. RESULTS: A total of 24 mothers from across Australia were interviewed.
      Mothers are influenced by a number of factors in relation to their infant formula
      feeding practice. These factors include information on the formula tin and
      marketing from formula manufacturers, particularly in relation to choosing the
      type of formula. Their formula feeding practices are also influenced by their
      interpretation of infant cues, and the amount of formula in the bottle. Many
      mothers would like more information to aid their practices but barriers exist to
      accessing health professional advice and support, so mothers may rely on informal
      sources. Some women reported that the social environment surrounding infant
      feeding wherein breastfeeding is promoted as the best option leads a feeling of
      stigma when formula feeding. CONCLUSIONS: Additional support for parents' feeding
      their infants with formula is necessary. Health professionals and policy around
      infant formula use should include how formula information may be provided to
      parents who use formula in ways that do not undermine breastfeeding promotion.
      Further observational research should seek to understand the interaction between
      advice, interpretation of cues and the amount formula fed to infants.

PMID- 29368597
TI  - Deep learning of mutation-gene-drug relations from the literature.
AB  - BACKGROUND: Molecular biomarkers that can predict drug efficacy in cancer
      patients are crucial components for the advancement of precision medicine.
      However, identifying these molecular biomarkers remains a laborious and
      challenging task. Next-generation sequencing of patients and preclinical models
      have increasingly led to the identification of novel gene-mutation-drug
      relations, and these results have been reported and published in the scientific
      literature. RESULTS: Here, we present two new computational methods that utilize
      all the PubMed articles as domain specific background knowledge to assist in the
      extraction and curation of gene-mutation-drug relations from the literature. The
      first method uses the Biomedical Entity Search Tool (BEST) scoring results as
      some of the features to train the machine learning classifiers. The second method
      uses not only the BEST scoring results, but also word vectors in a deep
      convolutional neural network model that are constructed from and trained on
      numerous documents such as PubMed abstracts and Google News articles. Using the
      features obtained from both the BEST search engine scores and word vectors, we
      extract mutation-gene and mutation-drug relations from the literature using
      machine learning classifiers such as random forest and deep convolutional neural
      networks. Our methods achieved better results compared with the state-of-the-art
      methods. We used our proposed features in a simple machine learning model, and
      obtained F1-scores of 0.96 and 0.82 for mutation-gene and mutation-drug relation
      classification, respectively. We also developed a deep learning classification
      model using convolutional neural networks, BEST scores, and the word embeddings
      that are pre-trained on PubMed or Google News data. Using deep learning, the
      classification accuracy improved, and F1-scores of 0.96 and 0.86 were obtained
      for the mutation-gene and mutation-drug relations, respectively. CONCLUSION: We
      believe that our computational methods described in this research could be used
      as an important tool in identifying molecular biomarkers that predict drug
      responses in cancer patients. We also built a database of these mutation-gene
      drug relations that were extracted from all the PubMed abstracts. We believe that
      our database can prove to be a valuable resource for precision medicine
      researchers.

PMID- 29368598
TI  - Study protocol: a randomised controlled trial of supervised resistance training
      versus aerobic training in Sri Lankan adults with type 2 diabetes mellitus: SL
      DART study.
AB  - BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and cardiovascular
      diseases (CVD) is rising globally. T2DM is particularly problematic in South Asia
      with an estimated 10-15% of Sri Lankans diagnosed with the disease. Exercise is
      known to improve blood glucose, lipid profiles, blood pressure and adiposity, key
      goals in the management of T2DM. However, much of the evidence to date has been
      gained from white Caucasians who have a different body composition and disease
      profile compared to South Asians. Similarly, the recreational exercise culture is
      new to Sri Lankans and the effects of exercise on T2DM has not been studied in
      this population. METHODS: The Sri Lanka Diabetes Aerobic and Resistance Training
      (SL-DART) Study will be comprised of 2 components. Component 1 is a 12-week
      randomized controlled trial (RCT) to compare the effects of a supervised
      progressive resistance exercise program (RT) and aerobic exercise program (AT)
      with standard treatment/control (CN). Sedentary Sri Lankan adults with T2DM (aged
      35-65 years) and with no contraindications to exercise will be randomized into
      one of 3 groups (AT, RT, CN). Exercise sessions will be conducted 2 days/week for
      3 months. Baseline and post-intervention biochemical (glycemic control, lipid and
      liver profiles, inflammatory markers), anthropometric (height, weight, body
      circumferences), body composition, physical fitness, food preference (liking and
      wanting food) and quality of life parameters will be measured and compared
      between groups. Component 2 will be a qualitative study conducted immediately
      post-intervention via in-depth interviews to assess the barriers and facilitators
      for adherence to each exercise program. DISCUSSION: SL-DART Study represents one
      of the first adequately powered methodologically sound RCTs conducted in South
      Asia to assess the effects of resistance and aerobic exercise in participants
      with T2DM. Triangulation of quantitative and qualitative outcomes will enable the
      design of a culturally appropriate therapeutic physical activity intervention for
      Sri Lankans with T2DM, and the initiation of a professionally driven and
      specialized clinical exercise prescription service. TRIAL REGISTRATION: Sri Lanka
      Clinical Trials Registry; SLCTR/2016/017 . Date registered 17.06.2016. Universal
      trial number U1111-1181-7561.

PMID- 29368599
TI  - Effectiveness of nasal highflow in hypercapnic COPD patients is flow and leakage
      dependent.
AB  - BACKGROUND: Nasal Highflow (NHF) delivers a humidified and heated airflow via
      nasal prongs. Current data provide evidence for efficacy of NHF in patients with
      hypoxemic respiratory failure. Preliminary data suggest that NHF may decrease
      hypercapnia in hypercapnic respiratory failure. The aim of this study was to
      evaluate the mechanism of NHF mediated PCO2 reduction in patients with chronic
      obstructive pulmonary disease (COPD). METHODS: In 36 hypercapnic COPD patients
      (PCO2 > 45 mmHg), hypercapnia was evaluated by capillary gas sampling 1 h after
      NHF breathing under four conditions A to D with different flow rates and
      different degrees of leakage (A = 20 L/min, low leakage, two prongs, both inside;
      B = 40 L/min, low leakage, two prongs, both inside; C = 40 L/min, high leakage,
      two prongs, one outside and open; D = 40 L/min, high leakage, two prongs, one
      outside and closed). Under identical conditions, mean airway pressure was
      measured in the hypopharynx of 10 COPD patients. RESULTS: Hypercapnia
      significantly decreased in all patients. In patients with capillary PCO2 > 55
      mmHg (n = 26), PCO2 additionally decreased significantly by increased leakage
      and/or flow rate in comparison to lower leakage/ flow rate conditions (A = 94.2
      +/- 8.2%; B = 93.5 +/- 4.4%; C = 90.5 +/- 7.2%; D = 86.8 +/- 3.8%). The highest
      mean airway pressure was observed in patients breathing under condition B (2.3 +/
      1.6 mbar; p < 0.05). CONCLUSIONS: This study demonstrates effective PCO2
      reduction with NHF therapy in stable hypercapnic COPD patients. This effect does
      not correlate with an increase in mean airway pressure but with increased leakage
      and airflow, indicating airway wash out and reduction of functional dead space as
      important mechanisms of NHF therapy. These results may be useful when considering
      NHF treatment in hypercapnic COPD patients. TRIAL REGISTRATION: Clinical Trials:
      NCT02504814; First posted July 22, 2015.

PMID- 29368600
TI  - Correction to: electronic cigarette use behaviors and motivations among smokers
      and non-smokers.
AB  - After publication of the article [1], it has been brought to our attention that
      there is a funding acknowledgement missing. The authors would also like to
      include "Dr. Michael Joseph Blaha is funded by the American Heart Association
      Tobacco Regulatory Center, funding number: 1P50HL120163".

PMID- 29368601
TI  - Factors influencing the capacity of women to voice their concerns about maternal
      health services in the Muanda and Bolenge Health Zones, Democratic Republic of
      the Congo: a multi-method study.
AB  - BACKGROUND: This paper aims to identify factors that influence the capacity of
      women to voice their concerns regarding maternal health services at the local
      level. METHODS: A secondary analysis was conducted of the data from three studies
      carried out between 2013 and 2015 in the Democratic Republic of the Congo (DRC)
      in the context of a WOTRO initiative to improve maternal health services through
      social accountability mechanisms in the DRC. The data processing and analysis
      focused on data related to factors that influence the capacity of women to voice
      their concerns and on the characteristics of women that influence their ability
      to identify, and address specific problems. Data from 21 interviews and 12 focus
      group discussions (n = 92) were analysed using an inductive content analysis, and
      those from one household survey (n = 517) were summarized. RESULTS: The women
      living in the rural setting were mostly farmers/fisher-women (39.7%) or worked at
      odd jobs (20.3%). They had not completed secondary school (94.6%). Around one
      fifth was younger than 20 years old (21.9%). The majority of women could describe
      the health service they received but were not able to describe what they should
      receive as care. They had insufficient knowledge of the health services before
      their first visit. They were not able to explain the mandate of the health
      providers. The information they received concerned the types of healthcare they
      could receive but not the real content of those services, nor their rights and
      entitlements. They were unaware of their entitlements and rights. They believed
      that they were laypersons and therefore unable to judge health providers, but
      when provided with some tools such as a checklist, they reported some abusive and
      disrespectful treatments. However, community members asserted that the reported
      actions were not reprehensible acts but actions to encourage a woman and to make
      her understand the risk of delivery. CONCLUSIONS: Factors influencing the
      capacity of women to voice their concerns in DRC rural settings are mainly
      associated with insufficient knowledge and socio-cultural context. These findings
      suggest that initiatives to implement social accountability have to address
      community capacity-building, health providers' responsiveness and the socio
      cultural norms issues.

PMID- 29368603
TI  - Defining the normal appearance of the temporomandibular joints by magnetic
      resonance imaging with contrast: a comparative study of children with and without
      juvenile idiopathic arthritis.
AB  - BACKGROUND: Up to 80% of children with juvenile idiopathic arthritis (JIA)
      develop arthritis involving their temporomandibular joint (TMJ). Recent studies
      have questioned the sensitivity of an abnormal MRI in the diagnosis of active
      arthritis. METHODS: 122 children without arthritis undergoing contrast MRI of the
      head were prospectively consented to undergo a simultaneous contrast MRI of their
      TMJs. As a comparison point, the initial MRI of the TMJ of 35 newly diagnosed
      children with JIA were retrospectively scored. The presence and size of effusion
      and contrast enhancement were measured in the left TMJ in all subjects. RESULTS:
      62/122 (51%) controls compared to only 10/35 JIA (29%) patients had an effusion
      (p = 0.022). Contrast enhancement was present in >=97% of both groups, although
      the size of the enhancement was, on average, 0.2 mm larger in controls (1.1 +/-
      0.24 vs 0.88 +/- 0.27 mm, p <  0.001). Among JIA patients, the size of the
      enhancement correlated inversely with disease duration (r = - 0.475, p = 0.005).
      Chronic changes were present in none of the controls versus 2/35 (5.5%) of the
      JIA patients (p = 0.049). CONCLUSION: Findings consistent with minimally active
      TMJ arthritis appear to be equally likely in children with JIA as compared to non
      inflamed controls, while this and other studies confirm that chronic changes are
      specific to JIA. Thus, small amounts of effusion or contrast enhancement, in the
      absence of chronic changes, should be interpreted with caution.

PMID- 29368602
TI  - Long non-coding RNA implicated in the invasion and metastasis of head and neck
      cancer: possible function and mechanisms.
AB  - Head and neck cancer (HNC) ranks as the 6th most common malignancy across the
      world. Metastasis is a hallmark of cancer, primarily contributing to the relapse
      and poor prognosis of HNC. Recently, long noncoding RNAs (lncRNAs), previously
      considered as non-functional, are increasingly appreciated by scholars to play
      crucial roles in mediating HNC metastasis. LncRNAs, which are located in the
      nucleus and cytoplasm, mainly exert their function via epigenetic modification,
      transcriptional control and translational regulation. As several lncRNAs are
      presently demonstrated to participate in HNC metastasis, we make a summary of the
      functions and mechanisms regarding these lncRNAs. As shown in the literature,
      most lncRNAs appear to promote the metastasis of HNC. Hence, we primarily discuss
      the lncRNAs involved in enhancing metastasis. Additionally, more studies are
      needed to understand those lncRNAs without clear mechanisms. Furthermore, we
      introduced the upstream regulator for the aberrant expression of lncRNAs in HNC.
      Finally, we concisely addressed future research prospects of lncRNAs,
      particularly the interplay between lncRNAs and tumor immunity as well as lncRNA
      targeted therapeutic techniques, and we introduced clustered regularly
      interspaced short palindromic repeats (CRISPR)-Display as a possibly
      transformative tool to study lncRNAs. Although lncRNA research is still in the
      initial stage, it holds great promise to be applied as a prognosticator of HNC
      and a therapeutic target to inhibit HNC metastasis, which could significantly
      enhance the outcome of HNC patients.

PMID- 29368604
TI  - Long-acting bronchodilators improve exercise capacity in COPD patients: a
      systematic review and meta-analysis.
AB  - Background: We carried out a systematic review and meta-analysis with the aim to
      evaluate the efficacy of longactingbronchodilators on exercise capacity in COPD
      patients. Methods: The endpoints were the efficacy of long-acting bronchodilators
      (altogether, and by single classes)vs. placebo in modifying endurance time (ET),
      inspiratory capacity (IC) and dyspnea during exercise, taking into consideration
      the outcomes according to different patients' inclusion criteria and exercise
      methodology. Results: Twenty-two studies were deemed eligible for analysis.
      Weighted mean increase in ET resulted of 67 s(95% CI ranges from 55 to 79). For
      isotime IC and dyspnea during exercise, weighted improvements were 195 ml (162
      229), and - 0.41 units (- 0.56 to - 0.27), respectively. The increase in trough
      IC was 157 ml (138-175). We found a trend in favour of LAMA compared to LABA in
      terms of ET. In the 11 studies which reported a value of functional residual
      capacity > 120% as inclusion criterion, weighted mean increase in endurance time
      was 94 s (65 to 123); however we did not find any significant correlation between
      ET and mean trough IC (P: 0.593). The improvement of ET in the 5 studies using
      walking as exercise methodology resulted of 58 s (- 4 to 121). Conclusions: Long
      acting bronchodilators improve exercise capacity in COPD. The main effect of long
      acting bronchodilators seems to be a increase of basal IC rather than a
      modification of dynamic hyperinflation during exercise. The efficacy in terms of
      endurance time seems higher in studies which enrolled patients with
      hyperinflation, with a similar efficacy on walking or cycling.

PMID- 29368605
TI  - The influence of prenatal exposure to trans-fatty acids for development of
      childhood haematopoietic neoplasms (EnTrance): a natural societal experiment and
      a case-control study.
AB  - BACKGROUND: Little is known about the causes of childhood cancer, partly as not
      many children develop cancer, although childhood cancer is a leading cause of
      death by disease in the young. The young age of the children suggests that risk
      factors for childhood cancer may be present during pregnancy. Previous studies
      have shown that exposure to trans-fat, a type of unsaturated fat common in
      industrially produced foods (iTFA), has adverse health effects in adults,
      including the risk of developing cancer. Haematopoietic neoplasms are the most
      common cancer types among European children under the age of 15 years. This study
      will bring new knowledge as to whether trans-fat and other fatty acids may also
      increase the risk of developing haematopoietic neoplasms during childhood.
      METHODS: We will investigate if the Danish iTFA legislation ban, which radically
      reduced the use of iTFA in foodstuffs, influenced the risk of childhood
      haematopoietic neoplasms in children born either before or after the change in
      legislation, adjusting for relevant secular trends. Further, in a case-control
      study, we will examine if levels of fatty acids in dried blood spots from
      newborns can predict the risk of developing childhood haematopoietic neoplasms.
      Permission from the Danish Data Protection Agency and the Ethical Committee has
      been granted. DISCUSSION: The results from this study will provide important
      information about fatty acids in the mother's diet as a contributor to
      development of haematopoietic neoplasms during childhood, which may result in
      relevant preventive action. TRIAL REGISTRATION: Not relevant.

PMID- 29368606
TI  - PKN2 in colon cancer cells inhibits M2 phenotype polarization of tumor-associated
      macrophages via regulating DUSP6-Erk1/2 pathway.
AB  - BACKGROUND: Protein kinase N2 (PKN2) is a PKC-related serine/threonine-protein
      kinase. PKN2 is required for tumor cell migration, invasion and apoptosis.
      However, the functional role of PKN2 in regulating tumor associated macrophages
      (TAMs) polarization in colon cancer has never been reported. METHODS: PKN2
      expression in human colon cancer tissues was examined with immunohistochemistry
      (IHC). M1/M2 macrophage signatures were evaluated by RT-PCR, IHC and flow
      cytometry. The effects of PKN2 on tumor growth and TAM polarization were
      investigated both in vitro and in vivo. PKN2 targeted cytokines/pathway were
      analyzed by gene expression analysis and further confirmed by PCR, luciferase
      assay or western blot. Correlations between PKN2 and transcriptional factors for
      IL4 and IL10 were confirmed by ChIP-qPCR. The catalytic activities of PKN2 and
      DUSP6 were determined by kinase activity assay. Interactions between PKN2 and
      DUSP6 were confirmed by Co-IP. RESULTS: The expression of PKN2 in colon cancer
      cells predicted a favorable prognosis and was associated with low M2 macrophage
      content in human colon cancer tissues. PKN2 inhibited tumor growth in mice
      xenograft model and inhibited M2 phenotype polarization both in vitro and in
      vivo. Mechanistically, PKN2 suppresses the expression of IL4 and IL10 from colon
      cancer cells by inhibiting Erk1/2 phosphorylation, which is required for
      phosphorylation and binding of CREB and Elk-1 to the promoters of IL4 and IL10.
      DUSP6, which is phosphorylated and activated through direct association with
      PKN2, suppresses Erk1/2 activation. CONCLUSIONS: The expression of PKN2 in colon
      cancer cells suppresses tumor associated M2 macrophage polarization and tumor
      growth. Targeting PKN2 signaling pathway may provide a potential therapeutic
      strategy for colon cancer.

PMID- 29368607
TI  - Predictors of abnormal cytology among HPV-infected women in remote territories of
      French Guiana.
AB  - BACKGROUND: Cervical cancer prevention using cervical cytology is insufficiently
      sensitive, a significant proportion of HPV-infected women having normal cytology.
      The objective of the present study was to try to identify factors associated with
      abnormal cytology in HPV-infected women living in remote areas of French Guiana.
      METHODS: A study was conducted in women aged 20-65 years having HPV infections
      confirmed by HPV DNA detection using the GREINER-BIO-ONE kit. In addition to HPV
      testing, cytology was performed and classified as normal or abnormal. Demographic
      and life history variables, and infecting genotypes were compared between the
      normal and abnormal cytology groups. RESULTS: None of the demographic and life
      history variables were associated with cytology results. HPV genotype 53 was
      significantly associated with absence of cytological abnormalities whereas HPV
      52, 58, 16 and perhaps 33 and 66 were independently associated with a greater
      risk of cytological abnormalities. When grouping HPV genotypes in different
      species, only species 9 (HPV 16, 31, 33, 35, 52, 58, 67) was significantly
      associated with abnormal cytology AOR = 5.1 (95% CI = 2.3-11.2), P < 0.001.
      CONCLUSIONS: It was not possible to predict which HPV-infected women will have
      cytological abnormalities or notfrom anamnesis. In this study HPV 53 seemed more
      benign than other HPV genotypes. On the contrary, species n degrees 9, containing
      5 of the genotypes contained in the nonavalent HPV vaccine, was significantly
      associated with more cytological abnormalities. HPV testing and vaccination with
      the nonavalent vaccine should be implemented in these remote parts of French
      Guiana.

PMID- 29368608
TI  - Burden of asthma and COPD overlap (ACO) in Taiwan: a nationwide population-based
      study.
AB  - BACKGROUND: Patients with symptoms of both asthma and chronic obstructive
      pulmonary disease (COPD) may be classified with the term asthma-COPD overlap
      (ACO). ACO is of considerable interest as it is currently poorly characterised
      and has been associated with worse health outcomes and higher healthcare costs
      compared with COPD or asthma alone. Patients with ACO in Asia remain poorly
      described, and there is limited information regarding their resource utilisation
      compared with patients with asthma or COPD only. This study investigated the
      characteristics, disease burden and medical resource utilisation of patients with
      ACO in Taiwan. METHODS: This was a retrospective cohort study of patients
      identified from National Health Insurance (NHI) claims data in Taiwan in 2009
      2011. Patients were classified into incident ACO, COPD or asthma cohorts
      according to International Classification of Disease, ninth revision, clinical
      modification codes in claims. Eligible patients were >=40 years of age with 12
      months' continuous enrolment in the NHI programme pre- and post-index date (date
      of the first relevant medical claim). RESULTS: Patients with ACO (N = 22,328) and
      COPD (N = 69,648) were older and more likely to be male than those with asthma (N
      = 50,293). Patients with ACO had more comorbidities and exacerbations, with
      higher medication use: short-acting beta2-agonist prescriptions ranged from 30.4%
      of patients (asthma cohort) to 43.6% (ACO cohort), and inhaled
      corticosteroid/long-acting beta2-agonist combination prescriptions ranged from
      11.1% (COPD cohort) to 35.0% (ACO cohort) in the 12 months following index.
      Patients with ACO generally had the highest medication costs of any cohort (long
      acting muscarinic antagonist costs ranged from $227/patient [asthma cohort] to
      $349/patient [ACO cohort]); they also experienced more respiratory-related
      hospital visits than patients with asthma or COPD (mean outpatient/inpatient
      visits per patient post-index: 9.1/1.9 [ACO cohort] vs 5.7/1.4 [asthma cohort]
      and 6.4/1.7 [COPD cohort]). CONCLUSIONS: Patients with ACO in Taiwan experience a
      greater disease burden with greater healthcare resource utilisation, and higher
      costs, than patients with asthma or COPD alone.

PMID- 29368609
TI  - Combining information from a clinical data warehouse and a pharmaceutical
      database to generate a framework to detect comorbidities in electronic health
      records.
AB  - BACKGROUND: Medical coding is used for a variety of activities, from
      observational studies to hospital billing. However, comorbidities tend to be
      under-reported by medical coders. The aim of this study was to develop an
      algorithm to detect comorbidities in electronic health records (EHR) by using a
      clinical data warehouse (CDW) and a knowledge database. METHODS: We enriched the
      Theriaque pharmaceutical database with the French national Comorbidities List to
      identify drugs associated with at least one major comorbid condition and
      diagnoses associated with a drug indication. Then, we compared the drug
      indications in the Theriaque database with the ICD-10 billing codes in EHR to
      detect potentially missing comorbidities based on drug prescriptions. Finally, we
      improved comorbidity detection by matching drug prescriptions and laboratory test
      results. We tested the obtained algorithm by using two retrospective datasets
      extracted from the Rennes University Hospital (RUH) CDW. The first dataset
      included all adult patients hospitalized in the ear, nose, throat (ENT) surgical
      ward between October and December 2014 (ENT dataset). The second included all
      adult patients hospitalized at RUH between January and February 2015 (general
      dataset). We reviewed medical records to find written evidence of the suggested
      comorbidities in current or past stays. RESULTS: Among the 22,132 Common Units of
      Dispensation (CUD) codes present in the Theriaque database, 19,970 drugs (90.2%)
      were associated with one or several ICD-10 diagnoses, based on their indication,
      and 11,162 (50.4%) with at least one of the 4878 comorbidities from the
      comorbidity list. Among the 122 patients of the ENT dataset, 75.4% had at least
      one drug prescription without corresponding ICD-10 code. The comorbidity
      diagnoses suggested by the algorithm were confirmed in 44.6% of the cases. Among
      the 4312 patients of the general dataset, 68.4% had at least one drug
      prescription without corresponding ICD-10 code. The comorbidity diagnoses
      suggested by the algorithm were confirmed in 20.3% of reviewed cases.
      CONCLUSIONS: This simple algorithm based on combining accessible and immediately
      reusable data from knowledge databases, drug prescriptions and laboratory test
      results can detect comorbidities.

PMID- 29368610
TI  - The REVAMP natural experiment study: the impact of a play-scape installation on
      park visitation and park-based physical activity.
AB  - BACKGROUND: Designing parks that optimise visitation and support visitors to be
      active is important for public health. Yet there is very little evidence about
      whether playground refurbishment achieves these objectives. This study examined
      the impact of the installation of a play-scape in a large metropolitan park in
      Melbourne, Australia. METHODS: Natural experiment study (intervention vs
      control). At both parks, park visitation and physical activity were assessed
      before (T1, 2013) and after the intervention at 12 (T2, 2014) and 24 months (T3,
      2015). At each time point, measures included: observations of park visitors using
      the System for Observing Play and Recreation in Communities on four weekdays and
      four weekend days, objective monitors to record usage of the walking paths and
      the number of cars entering the park; and intercept surveys with adult park
      visitors. Cross-sectional surveys were conducted with local residents at T1 and
      T3. RESULTS: The observational data showed a 176% increase in park visitor counts
      from T1 to T2 (Incidence Rate Ratio (IRR) = 2.76, 95% CI = 1.04-7.33), at the
      intervention park relative to the control park. The intervention park had a 119%
      increase in counts of visitors observed engaging in MVPA from T1 to T2 (IRR =
      2.19, 95% CI = 1.14-4.20), and a 128% increase from T1 to T3 (IRR = 2.28, 95% CI
      = 1.19-4.38), relative to the control park. The relative increases in visitation 
      at the intervention park play-scape compared with the control park playground
      were highly statistically significant from both T1 to T2 (IRR = 18.12, 95% CI =
      5.51-59.59) and T1 to T3 (IRR = 15.05, 95% CI = 4.61-49.16). Similarly, there was
      a significant interaction between time and park with regard to the number of
      visitors observed engaging in MVPA in the play-scape/playground areas. The
      intercept survey data showed an increased odds of children's regular visitation
      to the intervention park at T2 (OR = 2.67, 95% CI = 1.08, 6.64), compared with
      T1, relative to the control park. The remaining results from the intercept
      survey, objective monitors and resident surveys showed no significant differences
      in visitation between the two parks. CONCLUSIONS: These findings confirm that a
      well-designed play-scape installation has the potential to increase park
      visitation and encourage visitors to be physically active. TRIAL REGISTRATION:
      Current controlled trial ISRCTN50745547 .

PMID- 29368611
TI  - Correction to: Use of autogenous onlay bone graft for uncontained tibial bone
      defects in primary total knee arthroplasty.
AB  - After the publication of this article [1] it came to the attention of the authors
      that there were 2 errors in the results section: 0.0.856 should be 0.856 and
      "this this difference" should have been "this difference".

PMID- 29368612
TI  - Enhanced clinical-scale manufacturing of TCR transduced T-cells using closed
      culture system modules.
AB  - BACKGROUND: Genetic engineering of T-cells to express specific T cell receptors
      (TCR) has emerged as a novel strategy to treat various malignancies. More
      widespread utilization of these types of therapies has been somewhat constrained
      by the lack of closed culture processes capable of expanding sufficient numbers
      of T-cells for clinical application. Here, we evaluate a process for robust
      clinical grade manufacturing of TCR gene engineered T-cells. METHODS: TCRs that
      target human papillomavirus E6 and E7 were independently tested. A 21 day process
      was divided into a transduction phase (7 days) and a rapid expansion phase (14
      days). This process was evaluated using two healthy donor samples and four
      samples obtained from patients with epithelial cancers. RESULTS: The process
      resulted in ~ 2000-fold increase in viable nucleated cells and high transduction
      efficiencies (64-92%). At the end of culture, functional assays demonstrated that
      these cells were potent and specific in their ability to kill tumor cells bearing
      target and secrete large quantities of interferon and tumor necrosis factor. Both
      phases of culture were contained within closed or semi-closed modules, which
      include automated density gradient separation and cell culture bags for the first
      phase and closed GREX culture devices and wash/concentrate systems for the second
      phase. CONCLUSION: Large-scale manufacturing using modular systems and semi
      automated devices resulted in highly functional clinical-grade TCR transduced T
      cells. This process is now in use in actively accruing clinical trials and the
      NIH Clinical Center and can be utilized at other cell therapy manufacturing sites
      that wish to scale-up and optimize their processing using closed systems.

PMID- 29368613
TI  - Comparison among perfect-C(r), zero-P(r), and plates with a cage in single-level
      cervical degenerative disc disease.
AB  - BACKGROUND: We intended to analyze the efficacy of a new integrated cage and
      plate device called Perfect-C for anterior cervical discectomy and fusion (ACDF)
      to cure single-level cervical degenerative disc disease. METHODS: We enrolled 148
      patients who were subjected to single-level ACDF with one of the following three
      surgical devices: a Perfect-C implant (41 patients), a Zero-P implant (36
      patients), or a titanium plate with a polyetheretherketone (PEEK) cage (71
      patients). We conducted a retrospective study to compare the clinical and
      radiological results among the three groups. RESULTS: The length of the
      operation, intraoperative blood loss, and duration of hospitalization were
      significantly lower in the Perfect-C group than in the Zero-P and plate-with-cage
      groups (P < 0.05). At the last follow-up visit, heterotopic ossification (HO) was
      not observed in any cases (0%) in the Perfect-C and Zero-P groups but was noted
      in 21 cases (30%) in the plate-with-cage group. The cephalad and caudal plate-to
      disc distance (PDD) and the cephalad and caudal PDD/anterior body height (ABH)
      were significantly greater in the Perfect-C and Zero-P groups than in the plate
      with-cage group (P < 0.05). Subsidence occurred in five cases (14%) in the
      Perfect-C group, in nine cases (25%) in the Zero-P group, and in 15 cases (21%)
      in the plate-with-cage group. Fusion occurred in 37 cases (90%) in the Perfect-C
      group, in 31 cases (86%) in the Zero-P group, and in 68 cases (95%) in the plate
      with-cage group. CONCLUSIONS: The Perfect-C, Zero-P, and plate-with-cage devices
      are effective for treating single-level cervical degenerative disc disease.
      However, the Perfect-C implant has many advantages over both the Zero-P implant
      and conventional plate-cage treatments. The Perfect-C implant was associated with
      shorter operation times and hospitalization durations, less blood loss, and lower
      subsidence rates compared with the Zero-P implant or the titanium plate with a
      PEEK cage.

PMID- 29368614
TI  - Molecular imaging of pulmonary diseases.
AB  - Imaging holds an important role in the diagnosis of lung diseases. Along with
      clinical tests, noninvasive imaging techniques provide complementary and valuable
      information that enables a complete differential diagnosis. Various novel
      molecular imaging tools are currently under investigation aimed toward achieving
      a better understanding of lung disease physiopathology as well as early detection
      and accurate diagnosis leading to targeted treatment. Recent research on
      molecular imaging methods that may permit differentiation of the cellular and
      molecular components of pulmonary disease and monitoring of immune activation are
      detailed in this review. The application of molecular imaging to lung disease is
      currently in its early stage, especially compared to other organs or tissues, but
      future studies will undoubtedly reveal useful pulmonary imaging probes and
      imaging modalities.

PMID- 29368615
TI  - Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic
      agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients:
      a nationwide cohort observational study.
AB  - OBJECTIVE: Metformin is the standard first-line drug for patients with Type 2
      diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA)
      remains unclear. We investigated the cardiovascular risk of various ADAs used as
      add-on medication to metformin in T2DM patients from a nationwide cohort.
      METHODS: T2DM patients using different add-on oral ADAs after an initial
      metformin therapy of > 90 days were identified from the Taiwan National Health
      Insurance Database. Five classes of ADAs, including sulphonylureas (SU),
      glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and
      dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The
      reference group was the SU added to metformin. Patients were excluded if aged <
      20 years, had a history of stroke or acute coronary syndrome (ACS), or were
      receiving insulin treatment. The primary outcomes included any major adverse
      cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and
      death. A Cox regression model was used to estimate the hazard ratio (HR) for
      MACE. RESULTS: A total of 26,742 patients receiving their add-on drug to
      metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n =
      808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6
      +/- 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin
      group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p =
      0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups
      showed a significantly lower risk of MACE. CONCLUSION: Both TZD and AGI, when
      used as an add-on drug to metformin were associated with lower MACE risk when
      compared with SU added to metformin in this retrospective cohort study. Trial
      registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered.

PMID- 29368616
TI  - Undetected dysglycaemia common in primary care patients treated for hypertension
      and/or dyslipidaemia: on the need for a screening strategy in clinical practice.
      A report from EUROASPIRE IV a registry from the EuroObservational Research
      Programme of the European Society of Cardiology.
AB  - BACKGROUND: Dysglycaemia defined as type 2 diabetes (T2DM) and impaired glucose
      tolerance (IGT), increases the risk of cardiovascular disease (CVD). The negative
      impact is more apparent in the presence of hypertension and/or dyslipidaemia.
      Thus, it seems reasonable to screen for dysglycaemia in patients treated for
      hypertension and/or dyslipidaemia. A simple screening algorithm would enhance the
      adoption of such strategy in clinical practice. OBJECTIVES: To test the
      hypotheses (1) that dysglycaemia is common in patients with hypertension and/or
      dyslipidaemia and (2) that initial screening with the Finnish Diabetes Risk Score
      (FINDRISC) will decrease the need for laboratory based tests. METHODS: 2395
      patients (age 18-80 years) without (i) a history of CVD or TDM2, (ii) prescribed
      blood pressure and/or lipid lowering drugs answered the FINDRISC questionnaire
      and had an oral glucose tolerance test (OGTT) and HbA1c measured. RESULTS:
      According to the OGTT 934 (39%) had previously undetected dysglycaemia (T2DM 19%,
      IGT 20%). Of patients, who according to FINDRISC had a low, moderate or slightly
      elevated risk 20, 34 and 41% and of those in the high and very high-risk category
      49 and 71% had IGT or T2DM respectively. The OGTT identified 92% of patients with
      T2DM, FPG + HbA1c 90%, FPG 80%, 2hPG 29% and HbA1c 22%. CONCLUSIONS: (1) The
      prevalence of dysglycaemia was high in patients treated for hypertension and/or
      dyslipidaemia. (2) Due to the high proportion of dysglycaemia in patients with
      low to moderate FINDRISC risk scores its initial use did not decrease the need
      for subsequent glucose tests. (3) FPG was the best test for detecting T2DM. Its
      isolated use is limited by the inability to disclose IGT. A pragmatic strategy,
      decreasing the demand for an OGTT, would be to screen all patients with FPG
      followed by OGTT in patients with IFG.

PMID- 29368618
TI  - Psychotropic drugs in Nepal: perceptions on use and supply chain management.
AB  - BACKGROUND: Psychotropic drugs play an important role in the treatment of mental,
      neurological and substance use disorders. Despite the advancement of the use of
      psycho-pharmaceuticals in the developed countries, the psychotropic drug
      production and supply chain management in low- and middle- income countries are
      still poorly developed. This study aims to explore the perceptions of
      stakeholders involved in all stages of the psychotropic drug supply chain about
      the need, quality, availability and effectiveness of psychotropic drugs, as well
      as barriers to their supply chain management. The study was conducted among 65
      respondents from the Kathmandu, Chitwan and Pyuthan districts, grouped into four
      categories: producers, promoters and distributors (N = 22), policy makers and
      government actors (N = 8), service providers (N = 21) and service users/family
      members (N = 14). RESULTS: The respondents reported that psychotropic drugs,
      despite having side effects, are 1) needed, 2) available in major regional
      centers and 3) are effective for treating mental health problems. The stigma
      associated with mental illness, however, forces patients and family members to
      hide their use of psychotropic drugs. The study found that the process of
      psychotropic drug supply chain management is similar to other general drugs, with
      the exceptions of strict pre-approval process, quantity restriction (for
      production and import), and mandatory record keeping. Despite these regulatory
      provisions, respondents believed that the misuse of psychotropic drugs is
      widespread and companies are providing incentives to prescribers and retailers to
      retain their brand in the market. CONCLUSIONS: The production and supply chain
      management of psychotropic drugs is influenced by the vested interests of
      pharmaceutical companies, prescribers and pharmacists. In the context of the
      government of Nepal's policy of integrating mental health into primary health
      care and increased consumption of psychotropic drugs in Nepal, there is a need
      for massive education and awareness as well as strict monitoring and supervision
      to avoid the misuse of psychotropic drugs.

PMID- 29368617
TI  - Ubiquitous giants: a plethora of giant viruses found in Brazil and Antarctica.
AB  - BACKGROUND: Since the discovery of giant viruses infecting amoebae in 2003, many
      dogmas of virology have been revised and the search for these viruses has been
      intensified. Over the last few years, several new groups of these viruses have
      been discovered in various types of samples and environments.In this work, we
      describe the isolation of 68 giant viruses of amoeba obtained from environmental
      samples from Brazil and Antarctica. METHODS: Isolated viruses were identified by
      hemacolor staining, PCR assays and electron microscopy (scanning and/or
      transmission). RESULTS: A total of 64 viruses belonging to the Mimiviridae family
      were isolated (26 from lineage A, 13 from lineage B, 2 from lineage C and 23 from
      unidentified lineages) from different types of samples, including marine water
      from Antarctica, thus being the first mimiviruses isolated in this extreme
      environment to date. Furthermore, a marseillevirus was isolated from sewage
      samples along with two pandoraviruses and a cedratvirus (the third to be isolated
      in the world so far). CONCLUSIONS: Considering the different type of samples, we
      found a higher number of viral groups in sewage samples. Our results reinforce
      the importance of prospective studies in different environmental samples,
      therefore improving our comprehension about the circulation anddiversity of these
      viruses in nature.

PMID- 29368619
TI  - Geographic patterns of poor HIV/AIDS care continuum in District of Columbia.
AB  - BACKGROUND: Concurrent with the UNAIDS 90-90-90 and NHAS plans, the District of
      Columbia (DC) launched its 90/90/90/50 plan (Plan) in 2015. The Plan proposes
      that by 2020, 90% of all DC residents will know their HIV status; 90% of
      residents living with HIV will be in sustained treatment; 90% of those in
      treatment will reach "Viral Suppression" and DC will achieve 50% reduction of new
      HIV cases. To achieve these goals targeted prevention strategies are imperative
      for areas where the relative risk (RR) of not being linked to care (NL), not
      retained in any care (NRC) and low viral suppression (NVSP) are highest in the
      District. These outcomes are denoted in this study as poor outcomes of HIV care
      continuum. This study applies the Bayesian model for RR for area specific random
      effects to identify the census tracts with poor HIV care continuum outcomes for
      DC. METHODS: This analysis was conducted using cases diagnosed from 2010 to 2015
      and reported to the surveillance system from the District of Columbia Department
      of Health (DC DOH), HIV/AIDS, Hepatitis, STD and TB Administration. The
      jurisdictions of the District of Columbia is divided into 179 census tracts. It
      is challenging to plot sparse data in 'small' local administrative areas,
      characteristically which may have a single-count datum for each geographic area.
      Bayesian methods overcome this problem by assimilating prior information to the
      underlying RR, making the predicted RR estimates robust. RESULTS: The RR of NL is
      higher in 59 (33%) out of 179 census tracts in DC. The RR of NRC was high in 46
      (26%) of the census tracts while 52 census tracts (29%) show a high risk of
      having NVSP among its residents. This study also identifies clear correlated
      heterogeneity or clustering is evident in the northern tracts of the district.
      CONCLUSION: The study finds census tracts with higher RR of poor linkage to care
      outcomes in the District. These results will inform the Plan which aims to
      increase targeted testing leading to early initiation of antiretroviral therapy.
      The uniqueness of this study lies in its translational scope where surveillance
      data can be used to inform local public health programs and enhance the quality
      of health for the people with HIV.

PMID- 29368620
TI  - Molecular profiling of lung cancer specimens and liquid biopsies using MALDI-TOF
      mass spectrometry.
AB  - BACKGROUND: Identification of predictive molecular alterations in lung
      adenocarcinoma is essential for accurate therapeutic decisions. Although several
      molecular approaches are available, a number of issues, including tumor
      heterogeneity, frequent material scarcity, and the large number of loci to be
      investigated, must be taken into account in selecting the most appropriate
      technique. MALDI-TOF mass spectrometry (MS), which allows multiplexed genotyping,
      has been adopted in routine diagnostics as a sensitive, reliable, fast, and cost
      effective method. Our aim was to test the reliability of this approach in
      detecting targetable mutations in non-small cell lung cancer (NSCLC). In
      addition, we also analyzed low-quality samples, such as cytologic specimens, that
      often, are the unique source of starting material in lung cancer cases, to test
      the sensitivity of the system. METHODS: We designed a MS-based assay for testing
      158 mutations in the EGFR, KRAS, BRAF, ALK, PIK3CA, ERBB2, DDR2, AKT, and MEK1
      genes and applied it to 92 NSCLC specimens and 13 liquid biopsies from another
      subset of NSCLC patients. We also tested the sensitivity of the method to
      distinguish low represented mutations using serial dilutions of mutated DNA.
      RESULTS: Our panel is able to detect the most common NSCLC mutations and the
      frequency of the mutations observed in our cohort was comparable to literature
      data. The assay identifies mutated alleles at frequencies of 2.5-10%. In
      addition, we found that the amount of DNA template was irrelevant to efficiently
      uncover mutated alleles present at high frequency. However, when using less than
      10 ng of DNA, the assay can detect mutations present in at least 10% of the
      alleles. Finally, using MS and a commercial kit for RT-PCR we tested liquid
      biopsy from 13 patients with identified mutations in cancers and detected the
      mutations in 4 (MS) and in 5 samples (RT-PCR). CONCLUSIONS: MS is a powerful
      method for the routine predictive tests of lung cancer also using low quality and
      scant tissues. Finally, after appropriate validation and improvement, MS could
      represent a promising and cost-effective strategy for monitoring the presence and
      percentage of the mutations also in non-invasive sampling.

PMID- 29368621
TI  - The CSF neurofilament light signature in rapidly progressive neurodegenerative
      dementias.
AB  - BACKGROUND: Neurofilament light chain protein (NfL) is a surrogate biomarker of
      neurodegeneration that has never been systematically tested, either alone or in
      combination with other biomarkers, in atypical/rapidly progressive
      neurodegenerative dementias (NDs). METHODS: Using validated, commercially
      available enzyme-linked immunosorbent assay kits, we measured cerebrospinal fluid
      (CSF) NfL, total tau (t-tau), phosphorylated tau, and beta-amyloid 42 in subjects
      with a neuropathological or clinical diagnosis of prion disease (n = 141),
      Alzheimer's disease (AD) (n = 73), dementia with Lewy bodies (DLB) (n = 35), or
      frontotemporal lobar degeneration (FTLD) (n = 44). Several cases with an
      atypical/rapidly progressive course were included in each group. We evaluated the
      diagnostic accuracy of every CSF biomarker and their combinations by ROC curve
      analyses. RESULTS: In each patient group CSF NfL showed higher levels than in
      control subjects, reaching the highest values in those with Creutzfeldt-Jakob
      disease (CJD). In the latter, NfL showed a divergent, subtype-specific
      correlation with t-tau, depending on the degree of subcortical involvement and
      disease duration. Most significantly, patients with classic sporadic CJD (sCJD)
      MM1 showed a significantly lower concentration of CSF NfL than those with sCJD
      MV2, despite the much higher t-tau levels and the more rapid clinical course.
      High NfL levels were also detected in most atypical CJD cases, showing a disease
      duration longer than 2 years and/or borderline/negative results in other CSF
      assays (e.g., 14-3-3, t-tau, and prion real-time quaking-induced conversion).
      Rapidly progressive/atypical cases showed higher NfL levels than typical patients
      in FTLD, but not in AD or DLB. NfL showed accuracy similar to that of t-tau in
      discriminating CJD from other NDs, but it had higher efficacy in differentiating
      atypical forms, especially in regard to Alzheimer's disease. CONCLUSIONS: The
      present data indicate that CSF NfL and t-tau levels reflect distinct
      pathophysiological mechanisms of neurodegeneration and support the clinical use
      of NfL as a fast screening biomarker for the differential diagnosis of
      atypical/rapidly progressive NDs.

PMID- 29368622
TI  - Evaluation of the Preschool Situational Self-Regulation Toolkit (PRSIST) Program
      for Supporting children's early self-regulation development: study protocol for a
      cluster randomized controlled trial.
AB  - BACKGROUND: For children with low self-regulation in the preschool years, the
      likelihood of poorer intellectual, health, wealth and anti-social outcomes in
      adulthood is overwhelming. Yet this knowledge has not yielded a framework for
      understanding self-regulatory change, nor generated particularly successful
      methods for enacting this change. Reconciling insights from cross-disciplinary
      theory, research and practice, this study seeks to implement a newly developed
      program of low-cost and routine practices and activities for supporting early
      self-regulatory development within preschool contexts and to evaluate its effect
      on children's self-regulation, executive function and school readiness; and
      educator perceived knowledge, attitudes and self-efficacy related to self
      regulation. METHODS/DESIGN: The Early Start to Self-Regulation study is a cluster
      randomized, controlled trial for evaluating benefits of the Preschool Situational
      Self-Regulation Toolkit (PRSIST) program, when implemented by early childhood
      educators, compared with routine practice. The PRSIST program combines
      professional learning, adult practices, child activities and connections to the
      home to support children's self-regulation development. Fifty preschool centers
      in New South Wales, Australia, will be selected to ensure a range of
      characteristics, namely: National Quality Standards (NQS) ratings, geographic
      location and socioeconomic status. After collection of baseline child and
      educator data, participating centers will then be randomly allocated to one of
      two groups, stratified by NQS rating: (1) an intervention group (25 centers) that
      will implement the PRSIST program; or (2) a control group (25 centers) that will
      continue to engage in practice as usual. Primary outcomes at the child level will
      be two measures of self-regulation: Head-Toes-Knees-Shoulders task and the PRSIST
      observational assessment. Secondary outcomes at the child level will be adult
      reported measures of child self-regulation, executive function and school
      readiness. Outcomes at the educator level will involve a survey of their
      perceived knowledge, attitudes and self-efficacy for supporting children's self
      regulatory development. In all cases, data collectors will be blinded to group
      allocation. DISCUSSION: This is the first randomized controlled trial of a new
      program to foster early self-regulation, using low-cost practices and activities
      that are aligned with early-years contexts, routines and practices. Results will
      provide important information about the efficacy of this approach and evaluate
      its underlying model of self-regulatory change. TRIAL REGISTRATION: Australian
      New Zealand Clinical Trials Registry, ACTRN12617001568303 . Registered on 21
      November 2017.

PMID- 29368624
TI  - Efficacy of ursolic acid against Echinococcus granulosus in vitro and in a murine
      infection model.
AB  - BACKGROUND: Cystic echinococcosis is a global public health problem; however, the
      drugs (albendazole and mebendazole) currently recommended by WHO for its
      treatment, have limited efficacy. Therefore, novel drugs are required to provide
      more choices for the treatment of this disease. METHODS: The anthelmintic effects
      of ursolic acid (UA) were tested on Echinococcus granulosus protoscoleces,
      germinal cells and metacestodes in vitro. The in vivo efficacy of UA was
      investigated in mice following secondary infection with E. granulosus.
      Furthermore, the corresponding ultrastructural damage induced by UA was evaluated
      by electron microscopy. RESULTS: In vitro, 45.95 +/- 5.30% of protoscoleces were
      killed by UA at 40 MUg/ml, while the growth of more than 90% of germinal cells
      was inhibited by UA at 10 to 40 MUg/ml. The same effect was observed in
      metacestodes 7 days after treatment with UA at 10, 20 and 40 MUg/ml, and more
      than 50% of metacestodes showed loss of integrity at the end of the experiment.
      In vivo, metacestode weight was significantly reduced following oral
      administration of UA at 200 and 100 mg/kg (39.5 and 38.3%, respectively).
      Additionally, ultrastructural damage, such as alternations in germinal cell
      morphology and formation of vacuoles and lipid granules were observed in
      parasites treated with UA in vitro, while detachment of the germinal layer from
      the laminated layer was also seen in metacestodes in vivo. CONCLUSIONS: UA was
      demonstrated to exert parasiticidal activity against E. granulosus in vitro and
      in vivo, thus implicating UA as a potential anti-echinococcosis agent.

PMID- 29368623
TI  - ISD3: a particokinetic model for predicting the combined effects of particle
      sedimentation, diffusion and dissolution on cellular dosimetry for in vitro
      systems.
AB  - BACKGROUND: The development of particokinetic models describing the delivery of
      insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems
      has improved the basis for dose-response analysis, hazard ranking from high
      throughput systems, and now allows for translation of exposures across in vitro
      and in vivo test systems. Complimentary particokinetic models that address
      processes controlling delivery of both particles and released ions to cells, and
      the influence of particle size changes from dissolution on particle delivery for
      cell-culture systems would help advance our understanding of the role of
      particles and ion dosimetry on cellular toxicology. We developed ISD3, an
      extension of our previously published model for insoluble particles, by deriving
      a specific formulation of the Population Balance Equation for soluble particles.
      RESULTS: ISD3 describes the time, concentration and particle size dependent
      dissolution of particles, their delivery to cells, and the delivery and uptake of
      ions to cells in in vitro liquid test systems. We applied the model to calculate
      the particle and ion dosimetry of nanosilver and silver ions in vitro after
      calibration of two empirical models, one for particle dissolution and one for ion
      uptake. Total media ion concentration, particle concentration and total cell
      associated silver time-courses were well described by the model, across 2
      concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution
      data for 20 nm particles as a function of serum protein concentration, but
      successfully described the media and cell dosimetry time-course for both
      particles at all concentrations and time points. We also report the finding that
      protein content in media affects the initial rate of dissolution and the
      resulting near-steady state ion concentration in solution for the systems we have
      studied. CONCLUSIONS: By combining experiments and modeling, we were able to
      quantify the influence of proteins on silver particle solubility, determine the
      relative amounts of silver ions and particles in exposed cells, and demonstrate
      the influence of particle size changes resulting from dissolution on particle
      delivery to cells in culture. ISD3 is modular and can be adapted to new
      applications by replacing descriptions of dissolution, sedimentation and boundary
      conditions with those appropriate for particles other than silver.

PMID- 29368625
TI  - Perioperative fluid management in kidney transplantation: a black box.
AB  - The incidence of delayed graft function in patients undergoing kidney
      transplantation remains significant. Optimal fluid therapy has been shown to
      decrease delayed graft function after renal transplantation. Traditionally, the
      perioperative volume infusion regimen in this patient population has been guided
      by central venous pressure as an estimation of the patient's volume status and
      mean arterial pressure, but this is based on sparse evidence from mostly
      retrospective observational studies. Excessive volume infusion to the point of no
      further fluid responsiveness can damage the endothelial glycocalyx and is no
      longer considered to be the best approach. However, achievement of adequate flow
      to maintain sufficient tissue perfusion without maximization of cardiac filling
      remains a challenge. Novel minimally invasive technologies seem to reliably
      assess volume responsiveness, heart function and perfusion adequacy. Prospective
      comparative clinical studies are required to better understand the use of dynamic
      analyses of flow parameters for adequate fluid management in kidney transplant
      recipients. We review perioperative fluid assessment techniques and discuss
      conventional and novel monitoring strategies in the kidney transplant recipient.

PMID- 29368626
TI  - BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer,
      but not familial breast cancer.
AB  - BACKGROUND: Germline mutations in the BRIP1 gene have been described as
      conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in
      breast cancer (BC) pathogenesis remains controversial. METHODS: To assess the
      role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well
      characterized index patients with BC, 706 index patients with OC, and 2189
      geographically matched female controls were screened for loss-of-function (LoF)
      mutations and potentially damaging missense variants. All index patients met the
      inclusion criteria of the German Consortium for Hereditary Breast and Ovarian
      Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants.
      RESULTS: BRIP1 LoF mutations confer a high OC risk in familial index patients
      (odds ratio (OR) = 20.97, 95% confidence interval (CI) = 12.02-36.57, P < 0.0001)
      and in the subgroup of index patients with late-onset OC (OR = 29.91, 95% CI =
      14.99-59.66, P < 0.0001). No significant association of BRIP1 LoF mutations with
      familial BC was observed (OR = 1.81 95% CI = 1.00-3.30, P = 0.0623). In the
      subgroup of familial BC index patients without a family history of OC there was
      also no apparent association (OR = 1.42, 95% CI = 0.70-2.90, P = 0.3030). In 1027
      familial BC index patients with a family history of OC, the BRIP1 mutation
      prevalence was significantly higher than that observed in controls (OR = 3.59,
      95% CI = 1.43-9.01; P = 0.0168). Based on the negative association between BRIP1
      LoF mutations and familial BC in the absence of an OC family history, we conclude
      that the elevated mutation prevalence in the latter cohort was driven by the
      occurrence of OC in these families. Compared with controls, predicted damaging
      rare missense variants were significantly more prevalent in OC (P = 0.0014) but
      not in BC (P = 0.0693) patients. CONCLUSIONS: To avoid ambiguous results, studies
      aimed at assessing the impact of candidate predisposition gene mutations on BC
      risk might differentiate between BC index patients with an OC family history and
      those without. In familial cases, we suggest that BRIP1 is a high-risk gene for
      late-onset OC but not a BC predisposition gene, though minor effects cannot be
      excluded.

PMID- 29368627
TI  - Identification of membrane-associated proteins with pathogenic potential
      expressed by Corynebacterium pseudotuberculosis grown in animal serum.
AB  - OBJECTIVE: Previous works defining antigens that might be used as vaccine targets
      against Corynebacterium pseudotuberculosis, which is the causative agent of sheep
      and goat caseous lymphadenitis, have focused on secreted proteins produced in a
      chemically defined culture media. Considering that such antigens might not
      reflect the repertoire of proteins expressed during infection conditions, this
      experiment aimed to investigate the membrane-associated proteins with pathogenic
      potential expressed by C. pseudotuberculosis grown directly in animal serum.
      RESULTS: Its membrane-associated proteins have been extracted using an organic
      solvent enrichment methodology, followed by LC-MS/MS and bioinformatics analysis
      for protein identification and classification. The results revealed 22 membrane
      associated proteins characterized as potentially pathogenic. An interaction
      network analysis indicated that the four potentially pathogenic proteins ciuA,
      fagA, OppA4 and OppCD were biologically connected within two distinct network
      pathways, which were both associated with the ABC Transporters KEGG pathway.
      These results suggest that C. pseudotuberculosis pathogenesis might be associated
      with the transport and uptake of nutrients; other seven identified potentially
      pathogenic membrane proteins also suggest that pathogenesis might involve events
      of bacterial resistance and adhesion. The proteins herein reported potentially
      reflect part of the protein repertoire expressed during real infection conditions
      and might be tested as vaccine antigens.

PMID- 29368628
TI  - Extramammary Paget disease of the vulva: immunohistochemical analysis of
      neoangiogenesis and epithelial-mesenchymal transition markers expression.
AB  - BACKGROUND: Extra-mammary Paget's disease of the vulva (EMPDV) is an infrequent
      chronic disease that often recurs. The aim of the study was to assess the
      presence of neoangiogenesis and the expression of epithelial-mesenchymal
      transition (EMT) markers in EMPDV, and their potential correlation with stromal
      invasion. METHODS: All the women consecutively treated for EMPDV at our
      Institute, between January 2011 and December 2014, were studied for
      neoangiogenesis, analysed by microvessel density (MVD) using antibodies against
      CD31 and CD34. Immunohistochemical expression of E- / N-cadherin, beta-catenin
      and SLUG was also evaluated. In each slide, three fields with the highest number
      of capillaries and small venules were identified at low power. In these three
      fields, the highest vessel density (HVD) and the average vessel density (AVD) at
      200* and 400* magnification were counted. Immunohistochemical reactions for non
      vascular markers were semiquantitatively scored by two pathologists, using a
      three-tier scale. RESULTS: Seventeen cases of EMPDV (including 10 cases of
      invasive disease) were included. The AVD at 200* and 400* and the HVD at 400*
      magnification were significantly associated with invasive EMPDV (p = 0.02, 0.03,
      0.03 respectively). No significant correlation between MVD, EMT-markers
      expression and risk of recurrence was detected. CONCLUSION: These results
      indicate that MVD, as a measure of neoangiogenesis, may be associated with
      histological progression of EMPDV. EMT could also be linked to an invasive
      potential of EMPDV but larger series are required to confirm this hypothesis.

PMID- 29368630
TI  - Applying the ROBINS-I tool to natural experiments: an example from public health.
AB  - BACKGROUND: A new tool to assess Risk of Bias In Non-randomised Studies of
      Interventions (ROBINS-I) was published in Autumn 2016. ROBINS-I uses the Cochrane
      approved risk of bias (RoB) approach and focusses on internal validity. As such,
      ROBINS-I represents an important development for those conducting systematic
      reviews which include non-randomised studies (NRS), including public health
      researchers. We aimed to establish the applicability of ROBINS-I using a group of
      NRS which have evaluated non-clinical public health natural experiments. METHODS:
      Five researchers, all experienced in critical appraisal of non-randomised
      studies, used ROBINS-I to independently assess risk of bias in five studies which
      had assessed the health impacts of a domestic energy efficiency intervention.
      ROBINS-I assessments for each study were entered into a database and checked for
      consensus across the group. Group discussions were used to identify reasons
      underpinning lack of consensus for specific questions and bias domains. RESULTS:
      ROBINS-I helped to systematically articulate sources of bias in NRS. However, the
      lack of consensus in assessments for all seven bias domains raised questions
      about ROBINS-I's reliability and applicability for natural experiment studies.
      The two RoB domains with least consensus were selection (Domain 2) and
      performance (Domain 4). Underlying the lack of consensus were difficulties in
      applying an intention to treat or per protocol effect of interest to the studies.
      This was linked to difficulties in determining whether the intervention status
      was classified retrospectively at follow-up, i.e. post hoc. The overall risk of
      bias ranged from moderate to critical; this was most closely linked to the
      assessment of confounders. CONCLUSION: The ROBINS-I tool is a conceptually
      rigorous tool which focusses on risk of bias due to the counterfactual.
      Difficulties in applying ROBINS-I may be due to poor design and reporting of
      evaluations of natural experiments. While the quality of reporting may improve in
      the future, improved guidance on applying ROBINS-I is needed to enable existing
      evidence from natural experiments to be assessed appropriately and consistently.
      We hope future refinements to ROBINS-I will address some of the issues raised
      here to allow wider use of the tool.

PMID- 29368629
TI  - Evidence of porcine epidemic diarrhea virus (PEDV) shedding in semen from
      infected specific pathogen-free boars.
AB  - In 2013, PED emerged for the first time in the United States (US). The porcine
      epidemic diarrhea virus (PEDV) spread quickly throughout North America. Infection
      with PEDV causes watery diarrhea and up to 100% mortality in piglets,
      particularly for highly pathogenic non-InDel strains circulating in the US. PEDV
      is mainly transmitted by the fecal-oral route. Transmission via the venereal
      route has been suspected but not previously investigated. The aim of the study
      was to determine if PEDV could be detected in semen from infected specific
      pathogen-free (SPF) boars inoculated with a PEDV US non-InDel strain suggesting
      venereal transmission may occur. Two boars orally inoculated with PEDV showed
      clinical signs and virus shedding in feces. Transient presence of the PEDV genome
      was detected by RT-qPCR in the seminal (5.06 * 102 to 2.44 * 103 genomic
      copies/mL) and sperm-rich fraction of semen (5.64 * 102 to 3.40 * 104 genomic
      copies/mL) and a longer duration of viral shedding was observed in the sperm-rich
      fraction. The evidence of PEDV shedding in semen raises new questions in term of
      disease spread within the pig population with the use of potentially contaminated
      semen.

PMID- 29368631
TI  - Response to 'Increasing value and reducing waste in data extraction for
      systematic reviews: tracking data in data extraction forms'.
AB  - ?: This is a response to a Letter. Data abstraction is a time-consuming and error
      prone systematic review task. Shokraneh and Adams categorize available techniques
      for tracking data during data abstraction into three methods: simple annotation,
      descriptive addressing, and Cartesian coordinate system. While we agree with the
      categorization of the techniques, we disagree with the authors' statement that
      descriptive addressing is a PDF-independent method, i.e., any sort of descriptive
      addressing must reference a specific version of PDF file and not just any PDF of
      said report. Different versions of PDFs of the same report might place text and
      tables on different locations of the same page and/or on different pages.
      Consequently, it is our opinion that any kind of source location information
      should be accompanied by the source or linked by an intermediary service such as
      the Data Abstraction Assistant (DAA).

PMID- 29368632
TI  - Serum suPAR and syndecan-4 levels predict severity of community-acquired
      pneumonia: a prospective, multi-centre study.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of death
      worldwide and occurs with variable severity. There are few studies focused on the
      expression of soluble urokinase-type plasminogen activator receptor (suPAR) and
      syndecan-4 in patients with CAP. METHODS: A prospective, multi-centre study was
      conducted between January 2014 and December 2016. A total of 103 patients with
      severe CAP (SCAP), 149 patients with non-SCAP, and 30 healthy individuals were
      enrolled. Clinical data were recorded for all enrolled patients. Serum suPAR and
      syndecan-4 levels were determined by quantitative enzyme-linked immunosorbent
      assay. The t test and Mann-Whitney U test were used to compare between two
      groups; one-way analysis of variance and the Kruskal-Wallis test were used to
      compare multiple groups. Correlations were assessed using Pearson and Spearman
      tests. Area under the curve (AUCs), optimal threshold values, sensitivity, and
      specificity were calculated. Survival curves were constructed and compared by log
      rank test. Regression analyses assessed the effect of multiple variables on 30
      day survival. RESULTS: suPAR levels increased in all patients with CAP,
      especially in severe cases. Syndecan-4 levels decreased in patients with CAP,
      especially in non-survivors. suPAR and syndecan-4 levels were positively and
      negatively correlated with severity scores, respectively. suPAR exhibited high
      accuracy in predicting SCAP among patients with CAP with an AUC of 0.835 (p <
      0.001). In contrast, syndecan-4 exhibited poor diagnostic value for predicting
      SCAP (AUC 0.550, p = 0.187). The AUC for predicting mortality in patients with
      SCAP was 0.772 and 0.744 for suPAR and syndecan-4, respectively; the respective
      prediction threshold values were 10.22 ng/mL and 6.68 ng/mL. Addition of both
      suPAR and syndecan-4 to the Pneumonia Severity Index significantly improved their
      prognostic accuracy, with an AUC of 0.885. Regression analysis showed that suPAR
      >=10.22 ng/mL and syndecan-4 <= 6.68 ng/mL were reliable independent markers for
      prediction of 30-day survival. CONCLUSION: suPAR exhibits high accuracy for both
      diagnosis and prognosis of SCAP. Syndecan-4 can reliably predict mortality in
      patients with SCAP. Addition of both suPAR and syndecan-4 to a clinical scoring
      method could improve prognostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT03093220 . Registered on 28 March 2017 (retrospectively registered).

PMID- 29368633
TI  - Implementing a larviciding efficacy or effectiveness control intervention against
      malaria vectors: key parameters for success.
AB  - During the last decade, scale-up of vector control tools such as long-lasting
      insecticidal nets (LLINs) and indoor residual spraying (IRS) contributed to the
      reduction of malaria morbidity and mortality across the continent. Because these
      first line interventions are now affected by many challenges such as insecticide
      resistance, change in vector feeding and biting behaviour, outdoor malaria
      transmission and adaptation of mosquito to polluted environments, the World
      Health Organization recommends the use of integrated control approaches to
      improve, control and elimination of malaria. Larviciding is one of these
      approaches which, if well implemented, could help control malaria in areas where
      this intervention is suitable. Unfortunately, important knowledge gaps remain in
      its successful application. The present review summarises key parameters that
      should be considered when implementing larviciding efficacy or effectiveness
      trials.

PMID- 29368634
TI  - Binding and entry of peste des petits ruminants virus into caprine endometrial
      epithelial cells profoundly affect early cellular gene expression.
AB  - Peste des petits ruminants virus (PPRV), the etiological agent of peste des
      petits ruminants (PPR), causes an acute or subacute disease in small ruminants.
      Although abortion is observed in an unusually large proportion of pregnant goats
      during outbreaks of PPR, the pathogenic mechanism underlying remains unclear.
      Here, the gene expression profile of caprine endometrial epithelial cells (EECs)
      infected with PPRV Nigeria 75/1 was determined by DNA microarray to investigate
      the cellular response immediately after viral entry. The microarray analysis
      revealed that a total of 146 genes were significantly dysregulated by PPRV
      internalization within 1 h post-infection (hpi). Of these, 85 genes were
      upregulated and 61 genes were downregulated. Most of these genes, including
      NFKB1A, JUNB, and IL1A, have not previously been reported in association with
      PPRV infection in goats. Following viral replication (24 hpi), the expression of
      307 genes were significantly upregulated and that of 261 genes were
      downregulated. The data for the genes differentially expressed in EECs were
      subjected to a time sequence profile analysis, gene network analysis and pathway
      analysis. The gene network analysis showed that 13 genes (EIF2AK3, IL10, TLR4,
      ZO3, NFKBIB, RAC1, HSP90AA1, SMAD7, ARG2, JUNB, ZFP36, APP, and IL1A) were
      located in the core of the network. We clearly demonstrate that PPRV infection
      upregulates the expression of nectin-4 after 1 hpi, which peaked at 24 hpi in
      EECs. In conclusion, this study demonstrates the early cellular gene expression
      in the caprine endometrial epithelial cells after the binding and entry of PPRV.

PMID- 29368635
TI  - Cerebral metabolic effects of strict versus conventional glycaemic targets
      following severe traumatic brain injury.
AB  - BACKGROUND: Optimal glycaemic targets for patients with severe traumatic brain
      injury remain unclear. The primary objective of this microdialysis study was to
      compare cerebral metabolism with strict versus conventional glycaemic control.
      METHODS: We performed a prospective single-centre randomised controlled within
      subject crossover study of 20 adult patients admitted to an academic
      neurointensive care unit with severe traumatic brain injury. Patients underwent
      randomised, consecutive 24-h periods of strict (4-7 mmol/L; 72-126 mg/dl) and
      conventional (<10 mmol/L; 180 mg/dl) glycaemic control with microdialysis
      measurements performed hourly. The first 12 h of each study period was designated
      as a 'washout' period, with the subsequent 12 h being the period of interest.
      RESULTS: Cerebral glucose was lower during strict glycaemia than with
      conventional control (mean 1.05 [95% CI 0.58-1.51] mmol/L versus 1.28 [0.81-1.74]
      mmol/L; P = 0.03), as was lactate (3.07 [2.44-3.70] versus 3.56 [2.81-4.30]; P <
      0.001). There were no significant differences in pyruvate or the lactate/pyruvate
      ratio between treatment phases. Strict glycaemia increased the frequency of low
      cerebral glucose (< 0.8 mmol/L; OR 1.91 [95% CI 1.01-3.65]; P < 0.05); however,
      there were no differences in the frequency of critically low glucose (< 0.2
      mmol/L) or critically elevated lactate/pyruvate ratio between phases.
      CONCLUSIONS: Compared with conventional glycaemic targets, strict blood glucose
      control was associated with lower mean levels of cerebral glucose and an
      increased frequency of abnormally low glucose levels. These data support
      conventional glycaemic targets following traumatic brain injury. TRIAL
      REGISTRATION: ISRCTN, ISRCTN19146279 . Retrospectively registered on 2 May 2014.

PMID- 29368636
TI  - A multi-center, randomized controlled clinical trial, cost-effectiveness and
      qualitative research of electroacupuncture with usual care for patients with non
      acute pain after back surgery: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Although pain after back surgery is known to be difficult to control,
      various treatment options are available to patients and physicians. A protocol
      for a confirmatory randomized controlled trial (RCT) on pain and function after
      back surgery was designed based on the results of a pilot trial. The aim of this
      study is to compare the effectiveness and safety of electroacupuncture (EA) with
      usual care (UC) versus UC alone on pain control and functional improvement after
      back surgery. METHODS/DESIGN: This study is a multi-center, randomized, assessor
      blinded trial with an active control conducted in conjunction with a cost
      effectiveness analysis and qualitative research. Participants with non-acute low
      back pain with or without leg pain after back surgery who have a Visual Analogue
      Scale (VAS) pain intensity score >= 50 mm will be randomly assigned to either the
      EA with UC group (n = 54) or the UC group (n = 54). Following randomization,
      participants in both groups will receive the same UC treatment twice a week for a
      four-week treatment period. Participants assigned to the EA with UC group will
      additionally receive EA twice a week for the same four-week period. The primary
      outcome measure will be assessed using a VAS pain intensity score for low back
      pain. The secondary outcomes will include the Oswestry Disability Index, EuroQol
      5-Dimension score, and drug intake. The primary and secondary outcomes will be
      measured at one, four, and eight weeks post randomization. DISCUSSION: The
      results of this study will provide evidence of the effectiveness and cost
      effectiveness of EA in managing postoperative pain following back surgery. In
      addition, the qualitative research results will help improve the quality of
      integrative medical interventions. TRIAL REGISTRATION: Clinical Research
      Information Service (CRIS), Republic of Korea, KCT0001939 . Registered on 8 June
      2016.

PMID- 29368637
TI  - Global avian influenza outbreaks 2010-2016: a systematic review of their
      distribution, avian species and virus subtype.
AB  - BACKGROUND: We conducted a systematic review to investigate avian influenza
      outbreaks and to explore their distribution, upon avian influenza subtype,
      country, avian species and other relating details as no comprehensive
      epidemiological analysis of global avian influenza outbreaks from 2010 to 2016
      exists. METHODS: Data was collated from four databases (Scopus, Web of Science
      Core Correlation, PubMed and SpringerLink electronic journal) and a global
      electronic reporting system (ProMED mail), using PRISMA and ORION systematic
      approaches. One hundred seventy three avian influenza virus outbreaks were
      identified and included in this review, alongside 198 ProMED mail reports.
      RESULTS: Our research identified that the majority of the reported outbreaks
      occurred in 2016 (22.2%). These outbreaks were located in China (13.6%) and
      referred to commercial poultry farms (56.1%). The most common subtype reported in
      these outbreaks was H5N1 (38.2%), while almost 82.5% of the subtypes were highly
      pathogenic avian influenza viruses. There were differences noticed between ProMED
      mail and the scientific literature screened. CONCLUSIONS: Avian influenza virus
      has been proved to be able to contaminate all types of avian species, including
      commercial poultry farms, wild birds, backyard domestic animals, live poultry,
      game birds and mixed poultry. The study focused on wet markets, slaughterhouses,
      wild habitats, zoos and natural parks, in both developed and developing
      countries. The impact of avian influenza virus seems disproportionate and could
      potentially burden the already existing disparities in the public health domain.
      Therefore, a collaboration between all the involved health sectors is considered
      to be more than necessary.

PMID- 29368638
TI  - Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor
      mutational burden, and beyond.
AB  - Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed
      clinical management of metastatic urothelial carcinoma and metastatic renal cell
      carcinoma. However, response rates are low, and biomarkers are needed to predict
      for treatment response. Immunohistochemical quantification of PD-L1 was developed
      as a promising biomarker in early clinical trials, but many shortcomings of the
      four different assays (different antibodies, disparate cellular populations, and
      different thresholds of positivity) have limited its clinical utility. Further
      limitations include the use of archival specimens to measure this dynamic
      biomarker. Indeed, until PD-L1 testing is standardized and can consistently
      predict treatment outcome, the currently available PD-L1 assays are not
      clinically useful in urothelial and renal cell carcinoma. Other more promising
      biomarkers include tumor mutational burden, profiles of tumor infiltrating
      lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker
      may be best but will need prospective testing to validate such a biomarker.

PMID- 29368640
TI  - Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and
      lacrimal duct-associated lymphoid tissue (LDALT) of mice.
AB  - BACKGROUND: The lymphatic vascular pattern in the head of mice has rarely been
      studied, due to problems of sectioning and immunostaining of complex bony
      structures. Therefore, the association of head lymphoid tissues with the
      lymphatics has remained unknown although the mouse is the most often used species
      in immunology. RESULTS: Here, we studied the association of nasal and
      nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month
      old mice. We performed paraffin sectioning of whole, decalcified heads, and
      immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and
      Podoplanin. Most parts of the nasal mucous membrane do not contain any
      lymphatics. Only the region of the inferior turbinates contains lymphatic
      networks, which are connected to those of the palatine. Nose-associated lymphoid
      tissue (NALT) is restricted to the basal parts of the nose, which contain
      lymphatics. NALT is continued occipitally and can be found at both sides along
      the sphenoidal sinus, again in close association with lymphatic networks. Nasal
      lymphatics are connected to those of the ocular region via a lymphatic network
      along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated
      lymphoid tissue (LDALT) has a dense supply with lymphatics. CONCLUSIONS: NALT and
      LDALT play a key role in the immune system of the mouse head, where they function
      as primary recognition sites for antigens. Using the dense lymphatic networks
      along the NLD described in this study, these antigens reach lymphatics near the
      palatine and are further drained to lymph nodes of the head and neck region. NALT
      and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we
      suggest a causative connection of lymphatic vessels and the development of
      lymphoid tissues.

PMID- 29368639
TI  - Role of HIV in the desire of procreation and motherhood in women living with HIV
      in Spain: a qualitative approach.
AB  - BACKGROUND: Improved antiretroviral treatments and decrease in vertical
      transmission of HIV have led to a higher number of women living with HIV to
      consider childbearing. However, stigma and social rejection result in specific
      challenges that HIV positive women with procreation intentions have to face with.
      Our objective was to in depth analyse elements shaping their desire for
      procreation and specifically investigate the impact of HIV. METHODS: A
      qualitative study was conducted through open interviews with 20 women living with
      HIV between 18 and 45 years of age, from the Spanish AIDS Research Network Cohort
      (CoRIS). Interviews were audio-recorded and transcribed. A content analysis was
      performed. RESULTS: HIV diagnosis is a turning point in women's sexual and
      emotional life that is experienced traumatically. HIV diagnosis is usually
      associated with the fear of an immediate death and the idea of social isolation.
      At this moment, women temporarily reject future motherhood or having a sexual
      life. HIV status is only disclosed to the closed social circle and partner
      support is essential in HIV diagnosis assimilation process. Health professionals
      provide information on assisted reproductive technology and on how to minimize
      risk of partner HIV transmission. Most of barriers for procreation acknowledged
      by women are not related to HIV. However, women fear vertical transmission and
      experience other barriers derived from HIV infection. In this context, pregnancy
      makes women feel themselves as "normal women" despite HIV. Motherhood is
      considered an element of compensation that helps them to cope with HIV diagnosis.
      All these elements make health professionals key actors: they provide information
      and support after HIV diagnosis. CONCLUSIONS: Barriers and drivers for
      procreation are similar among HIV positive women and general population. However,
      stigma and discrimination linked with HIV weigh in HIV positive women decision of
      motherhood. In this context, it is necessary to provide these women with the
      necessary counselling, guidance and resources to take decisions about procreation
      properly informed.

PMID- 29368641
TI  - Factors associated with the use of dietary supplements and over-the-counter
      medications in Japanese elderly patients.
AB  - BACKGROUND: The use of dietary supplements and over-the-counter (OTC) drugs is
      increasing, and there is adequate concern about potential harmful effects.
      However, there are limited reports on the concurrent use of nonprescription
      medications with prescription medications in elderly patients. Therefore, this
      study was conducted to describe the use of dietary supplements and OTC drugs, and
      to identify predictors for their use in elderly patients using medications
      prescribed for chronic diseases. METHODS: This was a cross-sectional study that
      enrolled 729 patients aged >=65 years with chronic diseases, between January and
      March 2016. Data regarding socio-demographic status, medical condition, number of
      prescriptions, use of nonprescription medications, and psychological status were
      collected using a self-administered questionnaire and by review of medical
      records. Data regarding use of dietary supplements and OTC drugs were analyzed
      using descriptive statistics. Logistic regression analysis was applied to
      investigate factors associated with the use of dietary supplements and OTC drugs.
      RESULTS: The regular use of nonprescription drugs was reported by 32.5% of
      patients. Vitamins were the most commonly used dietary supplements in elderly
      patients. Female sex, higher educational qualifications, and good economic status
      were identified as predictors for the use of nonprescription medications.
      Concurrent use of nonprescription medications with more than 5 prescription
      medications was detected in 12.2% of participants. The disclosure rate of the use
      of nonprescription medications by patients to the physician was 30.3%.
      CONCLUSION: The use of dietary supplements and OTC drugs was common in elderly
      patients with chronic diseases, and its use is associated with sex, education,
      and economic status. General practitioners (GPs) need to recognize the potential
      use of nonprescription medications, considering that polypharmacy was common and
      disclosure rate was low in this study.

PMID- 29368642
TI  - Systematic reporting to improve the emergency medical response to major
      incidents: a pilot study.
AB  - BACKGROUND: Major incidents affect us globally, and are occurring with increasing
      frequency. There is still no evidence-based standard regarding the best medical
      emergency response to major incidents. Currently, reports on major incidents are
      non-standardised and variable in quality. This pilot study examines the first
      systematic reports from a consensus-based, freely accessible database, aiming to
      identify how descriptive analysis of reports submitted to this database can be
      used to improve the major incident response. METHODS: Majorincidentreporting.net
      is a website collecting reports on major incidents using a standardised template.
      Data from these reports were analysed to compare the emergency response to each
      incident. RESULTS: Data from eight reports showed that effective triage by
      experienced individuals and the use of volunteers for transport were notable
      successes of the major incident response. Inadequate resources, lack of a common
      triage system, confusion over command and control and failure of communication
      were reported failures. The following trends were identified: Fires had the
      slowest times for several aspects of the response and the only three countries to
      have a single dialling number for all three emergency services had faster
      response times. Helicopter Emergency Medical services (HEMS) were used for
      transport and treatment in rural locations and for triage and treatment in urban
      locations. In two incidents, a major incident was declared before the arrival of
      the first Emergency Medical Services (EMS) personnel. CONCLUSION: This study
      shows that we can obtain relevant data from major incidents by using systematic
      reporting. Though the sample size from this pilot study is not large enough to
      draw any specific conclusions it illustrates the potential for future analyses.
      Identified lessons could be used to improve the emergency medical response to
      major incidents.

PMID- 29368643
TI  - Claudin expression during early postnatal development of the murine cochlea.
AB  - BACKGROUND: Claudins are major components of tight junctions, which form the
      paracellular barrier between the cochlear luminal and abluminal fluid
      compartments that supports the large transepithelial voltage difference and the
      large concentration differences of K+, Na+ and Ca2+ needed for normal cochlear
      function. Claudins are a family of more than 20 subtypes, but our knowledge about
      expression and localization of each subtype in the cochlea is limited. RESULTS:
      We examined by quantitative RT-PCR the expression of the mRNA of 24 claudin
      isoforms in mouse cochlea during postnatal development and localized the
      expression in separated fractions of the cochlea. Transcripts of 21 claudin
      isoforms were detected at all ages, while 3 isoforms (Cldn-16, - 17 and - 18)
      were not detected. Claudins that increased expression during development include
      Cldn-9, - 13, - 14, - 15, and -19v2, while Cldn-6 decreased. Those that do not
      change expression level during postnatal development include Cldn-1, - 2, - 3, -
      4, - 5, - 7, - 8, -10v1, -10v2, - 11, - 12, -19v1, - 20, - 22, and - 23. Our
      investigation revealed unique localization of some claudins. In particular, Cldn
      13 expression rapidly increases during early development and is mainly expressed
      in bone but only minimally in the lateral wall (including stria vascularis) and
      in the medial region (including the organ of Corti). No statistically significant
      changes in expression of Cldn-11, - 13, or - 14 were found in the cochlea of
      Slc26a4 -/- mice compared to Slc26a4 +/- mice. CONCLUSIONS: We demonstrated
      developmental patterns of claudin isoform transcript expression in the murine
      cochlea. Most of the claudins were associated with stria vascularis and organ of
      Corti, tissue fractions rich in tight junctions. However, this study suggests a
      novel function of Cldn-13 in the cochlea, which may be linked to cochlear bone
      marrow maturation.

PMID- 29368644
TI  - Differences in do-not-resuscitate orders, hospice care utilization, and late
      referral to hospice care between cancer and non-cancer decedents in a tertiary
      Hospital in Taiwan between 2010 and 2015: a hospital-based observational study.
AB  - BACKGROUND: In 2009, the Taiwanese national health insurance system substantially
      expanded hospice coverage for terminal cancer patients to include patients with
      end-stage brain, dementia, heart, lung, liver, and kidney diseases. This study
      aimed to evaluate differences in do-not-resuscitate (DNR) status and hospice care
      utilization between terminal cancer patients and advanced non-cancer patients
      after the policy change. METHODS: Data were obtained from the Death and Hospice
      Palliative Care Database of Taipei Veterans General Hospital in Taiwan. The
      differences between cancer and non-cancer patients who died in this hospital
      between 2010 and 2015 were analyzed in terms of patient characteristics, rates of
      DNR orders, hospice care utilization, number of living days after DNR order,
      duration of survival (DOS) after hospice care enrollment, and the rate of late
      referral to hospice care. RESULTS: Data for 8459 patients who died of cancer and
      major non-cancer terminal diseases were included. DNR order rate, hospice care
      utilization rate, and DOS were significantly higher for cancer patients than for
      non-cancer patients (p < 0.001, p < 0.001, and p < 0.001, respectively). The
      number of living days after DNR order and the late referral rate were
      significantly higher for non-cancer decedents than for cancer decedents (p <
      0.001 and p < 0.001, respectively). From 2010 to 2015, there were significantly
      increasing trends in the hospice utilization rate, number of living days after
      DNR order, and rate of late referral for the cancer group (p < 0.001, p = 0.001,
      and p < 0.001, respectively). For the non-cancer group, there were significantly
      increasing trends in the rate of DNR order, hospice utilization rate, and number
      of living days after DNR order (p < 0.001, p < 0.001, and p = 0.029,
      respectively). CONCLUSIONS: Further guidelines should be developed to help
      clinicians to promptly refer terminal cancer and non-cancer patients to hospice
      care. Considering the lower hospice utilization rate and the growing need for
      hospice care among terminal non-cancer patients, policymakers should consider how
      to improve the relevant levels of professional care to enhance the accessibility
      and availability of hospice care in Taiwan.

PMID- 29368645
TI  - Patients admitted to hospital after suicide attempt with violent methods compared
      to patients with deliberate self-poisoning -a study of background variables,
      somatic and psychiatric health and suicidal behavior.
AB  - BACKGROUND: In Norway, there are about 550 suicides recorded each year. The
      number of suicide attempts is 10-15 times higher. Suicide attempt is a major risk
      factor for suicide, in particular when violent methods are used. Suicide attempts
      with violent methods have hardly been studied in Norway. This study describes
      demographic, psychiatric and somatic health in patients admitted to somatic
      hospitals in Norway after suicide attempt by violent methods compared with
      suicide attempters using deliberate self-poisoning (DSP). METHODS: Patients
      admitted to somatic hospital after suicide attempt aged > 18 years were included
      in a prospective cohort study, enrolled from December 2010 to April 2015.
      Demographics (gender, age, marital and living condition, educational and
      employment status), previous somatic and psychological health were registered.
      Patients who had used violent methods were compared with patients admitted after
      suicide attempt by DSP. RESULTS: The study included 80 patients with violent
      methods and 81 patients with DSP (mean age both groups 42 yrs.). Violent methods
      used were cutting (34%), jumping from heights (32%), hanging (14%), others (10%),
      shooting (7%) and drowning (4%). Patients with violent methods had more often
      psychosis than patients admitted with DSP (14% vs 4%, p <  0.05), less anxiety
      disorders (4% vs 19%, p <  0.01) and less affective disorders (21% vs. 36%, p < 
      0.05). There were no significant differences between the numbers of patients who
      received psychiatric treatment at the time of the suicide attempt (violent 55%
      versus DSP 48%) or reported previous suicide attempt, 58% in patients with
      violent methods and 47% in DSP. Patients with violent methods stayed longer in
      hospital (14.3 (mean 8.3-20.3) vs. 2.3 (mean 1.6-3.1) days, p <  0.001), stayed
      longer in intensive care unit (5 days vs. 0.5 days, p <  0.001) and were in need
      of longer mechanical ventilation (1.4 vs 0.1 days, p <  0.001). CONCLUSIONS:
      Patients with violent methods had more often psychosis, less anxiety disorders
      and affective disorders than patients with DSP. Psychiatric treatment before the
      attempt and previous suicide attempt was not significantly different between the
      groups and about half of the patients in both groups were in psychiatric
      treatment at the time of the suicide attempt.

PMID- 29368646
TI  - PHENOS: a high-throughput and flexible tool for microorganism growth phenotyping
      on solid media.
AB  - BACKGROUND: Microbial arrays, with a large number of different strains on a
      single plate printed with robotic precision, underpin an increasing number of
      genetic and genomic approaches. These include Synthetic Genetic Array analysis,
      high-throughput Quantitative Trait Loci (QTL) analysis and 2-hybrid techniques.
      Measuring the growth of individual colonies within these arrays is an essential
      part of many of these techniques but is useful for any work with arrays.
      Measurement is typically done using intermittent imagery fed into complex image
      analysis software, which is not especially accurate and is challenging to use
      effectively. We have developed a simple and fast alternative technique that uses
      a pinning robot and a commonplace microplate reader to continuously measure the
      thickness of colonies growing on solid agar, complemented by a technique for
      normalizing the amount of cells initially printed to each spot of the array in
      the first place. We have developed software to automate the process of combining
      multiple sets of readings, subtracting agar absorbance, and visualizing colony
      thickness changes in a number of informative ways. RESULTS: The "PHENOS" pipeline
      (PHENotyping On Solid media), optimized for Saccharomyces yeasts, produces highly
      reproducible growth curves and is particularly sensitive to low-level growth. We
      have empirically determined a formula to estimate colony cell count from an
      absorbance measurement, and shown this to be comparable with estimates from
      measurements in liquid. We have also validated the technique by reproducing the
      results of an earlier QTL study done with conventional liquid phenotyping, and
      found PHENOS to be considerably more sensitive. CONCLUSIONS: "PHENOS" is a cost
      effective and reliable high-throughput technique for quantifying growth of yeast
      arrays, and is likely to be equally very useful for a range of other types of
      microbial arrays. A detailed guide to the pipeline and software is provided with
      the installation files at https://github.com/gact/phenos .

PMID- 29368647
TI  - MIR-708 promotes phagocytosis to eradicate T-ALL cells by targeting CD47.
AB  - Immunoevasion is a hallmark of cancer progression, and immune checkpoint blockade
      has emerged as a promising strategy for cancer treatment. microRNAs (miRNAs) are
      important negative regulators of gene expression in the immune system. Here, we
      demonstrate that miR-708 regulates CD47, a transmembrane protein that inhibits
      phagocytosis in T cell acute lymphoblastic leukemia. miR-708 directly targeted
      CD47 through binding to 3'UTR and is inversely correlated with CD47 expression.
      Functional studies showed that restoration of miR-708 expression in the T-ALL
      cell line is sufficient to promote phagocytosis by macrophages in the absence or
      presence of the anti-CD47 antibody to eradicate T-ALL cells, and inhibited tumor
      engraftment in vivo. Together, our findings suggest that miR-708 is a key
      negative regulator of CD47 and may serve as an attractive candidate for
      immunotherapy of T-ALL.

PMID- 29368648
TI  - Food triggers and inherited metabolic disorders: a challenge to the pediatrician.
AB  - Several disorders should be considered in the case of newborns and infants
      experiencing acute or recurrent symptoms after food ingestion. Immune-mediated
      adverse food reactions are the most frequent and always to be considered.
      Nevertheless, in the extensive differential diagnosis, clinicians should also
      include inherited metabolic disorders (IMDs).This review reports clinical
      features and diagnostic aspects of the most common IMDs that may present with
      acute manifestations triggered by food intake. Major focus will be amino acid and
      protein metabolism defects and carbohydrate disorders.Nowadays, for many of these
      disorders the risk of an acute presentation triggered by food has been decreased
      by the introduction of expanded newborn screening (NBS). Nevertheless, clinical
      suspicion remains essential because some IMDs do not have still reliable markers
      for NBS and a false negative screening result may occur.The aim of this review is
      to help pediatricians to take these rare inherited disorders into account in the
      differential diagnosis of acute or recurrent gastrointestinal symptoms related to
      food intake, which may avoid delayed diagnosis and potentially life-threatening
      consequences.

PMID- 29368649
TI  - Secondary pulmonary alveolar proteinosis: a single-center retrospective study (a
      case series and literature review).
AB  - BACKGROUND: Secondary pulmonary alveolar proteinosis (sPAP) is an extremely rare
      disease. The clinical features of sPAP patients remain to be summarizeds.
      METHODS: Patients pathologically diagnosed with PAP and with negative results for
      anti-granulocyte macrophage colony stimulating factor (GM-CSF) autoantibodies
      from Peking Union Medical College Hospital between January 2000 and July 2016
      were retrospectively studied. The PubMed database was also searched for
      literature to collect published cases. RESULTS: In our center, nine patients were
      diagnosed as sPAP with a median age of 37 years. Hematological disorders,
      including myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and
      pulmonary tuberculosis (TB) infection were the underlying diseases. Cases
      secondary to MDS had very poor prognosis as all of them survived less than 2
      years after their diagnosis, while those secondary to TB had favorable prognosis.
      Only 33.3% of cases showed interlobular septal thickening in our sPAP group.
      Through literature review, 164 sPAP cases were collected. The age at diagnosis
      was 45.0 +/- 14.8 years old and the gender radio was 1.20:1 (M:F). 61.9% of cases
      were diagnosed by bronchoscopy. MDS and CML were common underlying diseases in
      34.1% and 15.2% of patients, respectively. Patients with sPAP secondary to
      hematological diseases had a short survival time and half of them died within
      14.95 months after diagnosis. CONCLUSIONS: MDS and TB infection were the most
      frequent underlying causes of sPAP in this single-center research in China, with
      cases secondary to MDS having a poor survival rate. sPAP was more likely to be
      secondary to hematological disorders, especially MDS and CML and had a fairly
      poor prognosis in published cases. sPAP should be suspected in PAP patients whose
      CT scan presents only ground-glass opacities without interlobular septal
      thickening.

PMID- 29368650
TI  - Association of depression with evolution of heart failure in patients with type 2
      diabetes mellitus.
AB  - BACKGROUND: Depression is a prevalent, independent predictor of mortality in
      patients with heart failure (HF). Depression is also common in type 2 diabetes
      mellitus (T2DM), which is itself an important risk factor for HF. However,
      association of depression with incident HF in T2DM is undefined. The aim of the
      present study was to evaluate the predictive value of depression in predicting
      incident HF in a community-based cohort of asymptomatic patients with T2DM.
      METHODS: We prospectively recruited 274 asymptomatic T2DM patients >= 65 years
      (age 71 +/- 4 year, 56% men) with preserved EF and no ischemic heart disease from
      a community-based population. The Patient Health Questionnaire 9 (PHQ-9) was used
      to detect depression, and LV dysfunction was sought with a comprehensive
      echocardiogram, including LV hypertrophy (LVH) and subclinical diastolic function
      (E/e'). Over a median follow-up of 1.5 years (range 0.5-3), 20 patients were lost
      to follow-up and 254 individuals were followed for outcomes. RESULTS: At
      baseline, depression was present in 9.5%, LVH was identified in 26% and reduced
      E/e' in 11%. Over a median follow-up of 1.5 years, 37 of 245 patients developed
      new-onset HF and 3 died, giving an event rate of 107/1000 person-years. In a
      competing-risks regression analysis, depression (adjusted HR 2.54, 95% CI 1.18
      5.46; p = 0.017) was associated with incident HF and had incremental predictive
      power to clinical, biochemical and echocardiographic variables. CONCLUSION:
      Depression is prevalent in asymptomatic elderly patients with T2DM, and
      depression independently and incrementally predicts incident HF.

PMID- 29368651
TI  - Early feeding of larger volumes of formula milk is associated with greater body
      weight or overweight in later infancy.
AB  - BACKGROUND: The relation between infant feeding and growth has been extensively
      evaluated, but studies examining the volume of formula milk consumption on infant
      growth are limited. This study aimed to examine the effects of early feeding of
      larger volumes of formula on growth and risk of overweight in later infancy.
      METHODS: In total, 1093 infants were studied prospectively. Milk records
      collected at 3 mo of age were used to define the following 3 feeding groups:
      breast milk feeding (BM, no formula), lower-volume formula milk feeding (LFM,
      <840 ml formula/d), and higher-volume formula milk feeding (HFM, >=840 ml
      formula/d). Body weight and length were measured at 3 time points of 3, 6 and 12
      mo of age. RESULTS: The results showed that the difference in weight and length
      between the HFM and BM infants was significant at 3 mo of age (P < 0.05) and
      continued until 12 mo of age (P < 0.001). The adjusted mean changes in weight-for
      length z-scores (WLZ) and BMI-for-age z-scores (BAZ) from 3 to 6 mo of age were
      significantly higher in HFM and LFM group than in BM group. Two-way interactions
      between feeding practice and age intervals were significant for WLZ changes (P =
      0.002) and BAZ changes (P = 0.017). Compared with BM-fed infants, infants fed
      with HFM had 1.60-fold (95% CI 1.05-2.44) higher odds of greater body weight (1SD
      < WLZ <=2 SD) at the age of 6 mo and 1.55-fold (95% CI 1.01-2.37) higher odds of
      greater body weight and 2.13-fold (95% CI 1.03-4.38) higher odds of overweight
      (WLZ > 2 SD) at the age of 12 mo. CONCLUSION: Feeding higher volumes of formula
      in early infancy is associated with greater body weight and overweight in later
      infancy.

PMID- 29368652
TI  - Novel GLI3 variant causing overlapped Greig cephalopolysyndactyly syndrome (GCPS)
      and Pallister-Hall syndrome (PHS) phenotype with agenesis of gallbladder and
      pancreas.
AB  - BACKGROUND: A proper balance between the activator and the repressor form of
      GLI3, a zinc-finger transcription factor downstream of hedgehog signaling, is
      essential for proper development of various organs during development. Mutations
      in different domains of the GLI3 gene underlie several congenital diseases
      including Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome
      (PHS). CASE PRESENTATION: Here, we describe the case of an overlapped phenotype
      of these syndromes with agenesis of the gallbladder and the pancreas, bearing a
      c.2155 C > T novel likely pathogenic variant of GLI3 gene by missense point
      mutation causing p.P719S at the proteolytic cleavage site. CONCLUSIONS: Although
      agenesis of the gallbladder and the pancreas is uncommon in GLI3 morphopathy, a
      slight difference in the gradient or the balance between activator and repressor
      in this case may hinder sophisticated spatial and sequential hedgehog signaling
      that is essential for proper development of gallbladder and pancreas from
      endodermal buds.

PMID- 29368653
TI  - New windows into retroviral RNA structures.
AB  - BACKGROUND: The multiple roles of both viral and cellular RNAs have become
      increasingly apparent in recent years, and techniques to model them have become
      significantly more powerful, enabling faster and more accurate visualization of
      RNA structures. MAIN BODY: Techniques such as SHAPE (selective 2'OH acylation
      analysed by primer extension) have revolutionized the field, and have been used
      to examine RNAs belonging to many and diverse retroviruses. Secondary structure
      probing reagents such as these have been aided by the development of faster
      methods of analysis either via capillary or next-generation sequencing, allowing
      the analysis of entire genomes, and of retroviral RNA structures within virions.
      Techniques to model the three-dimensional structures of these large RNAs have
      also recently developed. CONCLUSIONS: The flexibility of retroviral RNAs, both
      structural and functional, is clear from the results of these new experimental
      techniques. Retroviral RNA structures and structural changes control many stages
      of the lifecycle, and both the RNA structures themselves and their interactions
      with ligands are potential new drug targets. In addition, our growing
      understanding of retroviral RNA structures is aiding our knowledge of cellular
      RNA form and function.

PMID- 29368654
TI  - Identifying individual animal factors associated with Mycobacterium avium subsp.
      paratuberculosis (MAP) milk ELISA positivity in dairy cattle in the Midwest
      region of the United States.
AB  - BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP) is a widespread
      chronic disease of ruminants that causes severe economic losses to the dairy
      cattle industry worldwide. The objective of this study was to evaluate the
      association between individual cow MAP-ELISA and relevant milk production
      predictors in dairy cattle using data routinely collected as part of quality and
      disease control programs in the Midwest region of the U.S. Milk ELISA results of
      45,652 animals from 691 herds from November 2014 to August 2016 were analyzed.
      RESULTS: The association between epidemiological and production factors and ELISA
      results for MAP in milk was quantified using four individual-level mixed
      multivariable logistic regression models that accounted for clustering of animals
      at the farm level. The four fitted models were one global model for all the
      animals assessed here, irrespective of age, and one for each of the categories of
      < 4 year-old, 4-8 year-old, and > 8 year-old cattle, respectively. A small
      proportion (4.9%; n = 2222) of the 45,652 tested samples were MAP-seropositive.
      Increasing age of the animals and higher somatic cell count (SCC) were both
      associated with increased odds for MAP positive test result in the model that
      included all animals, while milk production, milk protein and days in milk were
      negatively associated with MAP milk ELISA. Somatic cell count was positively
      associated with an increased risk in the models fitted for < 4 year-old and 4-8
      year-old cattle. Variables describing higher milk production, milk protein
      content and days in milk were associated with significantly lower risk in the
      models for 4-8 year-old cattle and for all cattle. CONCLUSIONS: Our results
      suggest that testing cows with high SCC (> 26 * 1000/ml), low milk production and
      within the first 60 days of lactation may maximize the odds of detecting
      seropositive animals. These results could be useful in helping to design better
      surveillance strategies based in testing of milk.

PMID- 29368655
TI  - Deleterious genetic variants in ciliopathy genes increase risk of ritodrine
      induced cardiac and pulmonary side effects.
AB  - BACKGROUND: Ritodrine is a commonly used tocolytic to prevent preterm labour.
      However, it can cause unexpected serious adverse reactions, such as pulmonary
      oedema, pulmonary congestion, and tachycardia. It is unknown whether such adverse
      reactions are associated with pharmacogenomic variants in patients. METHODS:
      Whole-exome sequencing of 13 subjects with serious ritodrine-induced cardiac and
      pulmonary side-effects was performed to identify causal genes and variants. The
      deleterious impact of nonsynonymous substitutions for all genes was computed and
      compared between cases (n = 13) and controls (n = 30). The significant genes were
      annotated with Gene Ontology (GO), and the associated disease terms were
      categorised into four functional classes for functional enrichment tests. To
      assess the impact of distributed rare variants in cases with side effects, we
      carried out rare variant association tests with a minor allele frequency <= 1%
      using the burden test, the sequence Kernel association test (SKAT), and optimised
      SKAT. RESULTS: We identified 28 genes that showed significantly lower gene-wise
      deleteriousness scores in cases than in controls. Three of the identified genes
      CYP1A1, CYP8B1, and SERPINA7-are pharmacokinetic genes. The significantly
      identified genes were categorized into four functional classes: ion binding, ATP
      binding, Ca2+-related, and ciliopathies-related. These four classes were
      significantly enriched with ciliary genes according to SYSCILIA Gold Standard
      genes (P < 0.01), thus representing ciliary genes. Furthermore, SKAT showed a
      marginal trend toward significance after Bonferroni correction with Joubert
      Syndrome ciliopathy genes (P = 0.05). With respect to the pharmacokinetic genes,
      rs1048943 (CYP1A1) and rs1804495 (SERPINA7) showed a significantly higher
      frequency in cases than controls, as determined by Fisher's exact test (P < 0.05
      and P < 0.01, respectively). CONCLUSIONS: Ritodrine-induced cardiac and pulmonary
      side effects may be associated with deleterious genetic variants in ciliary and
      pharmacokinetic genes.

PMID- 29368657
TI  - Characteristics of Indigenous primary health care service delivery models: a
      systematic scoping review.
AB  - BACKGROUND: Indigenous populations have poorer health outcomes compared to their
      non-Indigenous counterparts. The evolution of Indigenous primary health care
      services arose from mainstream health services being unable to adequately meet
      the needs of Indigenous communities and Indigenous peoples often being excluded
      and marginalised from mainstream health services. Part of the solution has been
      to establish Indigenous specific primary health care services, for and managed by
      Indigenous peoples. There are a number of reasons why Indigenous primary health
      care services are more likely than mainstream services to improve the health of
      Indigenous communities. Their success is partly due to the fact that they often
      provide comprehensive programs that incorporate treatment and management,
      prevention and health promotion, as well as addressing the social determinants of
      health. However, there are gaps in the evidence base including the
      characteristics that contribute to the success of Indigenous primary health care
      services in providing comprehensive primary health care. This systematic scoping
      review aims to identify the characteristics of Indigenous primary health care
      service delivery models. METHOD: This systematic scoping review was led by an
      Aboriginal researcher, using the Joanna Briggs Institute Scoping Review
      Methodology. All published peer-reviewed and grey literature indexed in PubMed,
      EBSCO CINAHL, Embase, Informit, Mednar, and Trove databases from September 1978
      to May 2015 were reviewed for inclusion. Studies were included if they describe
      the characteristics of service delivery models implemented within an Indigenous
      primary health care service. Sixty-two studies met the inclusion criteria. Data
      were extracted and then thematically analysed to identify the characteristics of
      Indigenous PHC service delivery models. RESULTS: Culture was the most prominent
      characteristic underpinning all of the other seven characteristics which were
      identified - accessible health services, community participation, continuous
      quality improvement, culturally appropriate and skilled workforce, flexible
      approach to care, holistic health care, and self-determination and empowerment.
      CONCLUSION: While the eight characteristics were clearly distinguishable within
      the review, the interdependence between each characteristic was also evident.
      These findings were used to develop a new Indigenous PHC Service Delivery Model,
      which clearly demonstrates some of the unique characteristics of Indigenous
      specific models.

PMID- 29368656
TI  - Objective coding of content and techniques in workplace-based supervision of an
      EBT in public mental health.
AB  - BACKGROUND: Workplace-based clinical supervision as an implementation strategy to
      support evidence-based treatment (EBT) in public mental health has received
      limited research attention. A commonly provided infrastructure support, it may
      offer a relatively cost-neutral implementation strategy for organizations.
      However, research has not objectively examined workplace-based supervision of EBT
      and specifically how it might differ from EBT supervision provided in efficacy
      and effectiveness trials. METHODS: Data come from a descriptive study of
      supervision in the context of a state-funded EBT implementation effort. Verbal
      interactions from audio recordings of 438 supervision sessions between 28
      supervisors and 70 clinicians from 17 public mental health organizations (in 23
      offices) were objectively coded for presence and intensity coverage of 29
      supervision strategies (16 content and 13 technique items), duration, and
      temporal focus. Random effects mixed models estimated proportion of variance in
      content and techniques attributable to the supervisor and clinician levels.
      RESULTS: Interrater reliability among coders was excellent. EBT cases averaged
      12.4 min of supervision per session. Intensity of coverage for EBT content
      varied, with some discussed frequently at medium or high intensity (exposure) and
      others infrequently discussed or discussed only at low intensity (behavior
      management; assigning/reviewing client homework). Other than fidelity assessment,
      supervision techniques common in treatment trials (e.g., reviewing actual
      practice, behavioral rehearsal) were used rarely or primarily at low intensity.
      In general, EBT content clustered more at the clinician level; different
      techniques clustered at either the clinician or supervisor level. CONCLUSIONS:
      Workplace-based clinical supervision may be a feasible implementation strategy
      for supporting EBT implementation, yet it differs from supervision in treatment
      trials. Time allotted per case is limited, compressing time for EBT coverage.
      Techniques that involve observation of clinician skills are rarely used.
      Workplace-based supervision content appears to be tailored to individual
      clinicians and driven to some degree by the individual supervisor. Our findings
      point to areas for intervention to enhance the potential of workplace-based
      supervision for implementation effectiveness. TRIAL REGISTRATION: NCT01800266 ,
      Clinical Trials, Retrospectively Registered (for this descriptive study;
      registration prior to any intervention [part of phase II RCT, this manuscript is
      only phase I descriptive results]).

PMID- 29368658
TI  - HEALTH: laparoscopic supracervical hysterectomy versus second-generation
      endometrial ablation for the treatment of heavy menstrual bleeding: study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Heavy menstrual bleeding (HMB) is a common problem affecting
      approximately 1.5 million women in England and Wales with a major impact on their
      physical, emotional, social and material quality of life. It is the fourth most
      common reason why women attend gynaecology outpatient clinics and accounts for
      one-fifth of all gynaecology outpatient referrals. Initial treatment in primary
      care is medical - either by means of oral or injected medication or the
      levonorgestrel-intrauterine system (Mirena(r)). If medical treatment fails then
      surgical treatment can be offered, either endometrial ablation (EA), which
      destroys the lining of the cavity of the uterus (endometrium), or hysterectomy,
      i.e. surgical removal of the uterus. While effective, conventional hysterectomy
      is invasive and carries a risk of complications due to injury to other pelvic
      structures. The procedure can be simplified and complications minimised by
      undertaking a 'supracervical' hysterectomy where the cervix is left in situ and
      only the body of the uterus removed. Recent advances in endoscopic technologies
      have facilitated increased use of laparoscopic supracervical hysterectomy (LASH)
      which can be performed as a day-case procedure and is relatively easy for the
      surgeon to learn. HEALTH (Hysterectomy or Endometrial AbLation Trial for Heavy
      menstrual bleeding) aims to address the question 'Is LASH superior to second
      generation EA for the treatment of HMB in terms of clinical and cost
      effectiveness?' METHODS/DESIGN: Women aged < 50 years, with HMB, in whom medical
      treatment has failed and who are eligible for EA will be considered for trial
      entry. We aim to recruit women from approximately 30 active secondary care
      centres in the UK NHS who carry out both surgical procedures. All women who
      consent will complete a diary of pain symptoms from day 1 to day 14 after
      surgery, postal questionnaires at six weeks and six months after surgery and 15
      months post randomisation. Healthcare utilisation questions will also be
      completed at the six-week, six-month and 15-month time-points. DISCUSSION:
      Measuring the comparative effectiveness of LASH vs EA will provide the robust
      evidence required to determine whether the new technique should be adopted widely
      in the NHS. TRIAL REGISTRATION: International Standard Randomised Controlled
      Trials, ISRCTN49013893 . Registered on 28 January 2014.

PMID- 29368659
TI  - Pleiotropic alterations in gene expression in Latin American Fasciola hepatica
      isolates with different susceptibility to drugs.
AB  - BACKGROUND: Fasciola hepatica is the main agent of fasciolosis, a zoonotic
      disease affecting livestock worldwide, and an emerging food-borne disease in
      humans. Even when effective treatments are available, drugs are costly and can
      result in tolerance, liver damage and normally they do not prevent reinfection.
      Drug-resistant strains in livestock have been reported in various countries and,
      more worryingly, drug resistance in human cases has emerged in South America. The
      present study aims to characterize the transcriptome of two South American
      resistant isolates, the Cajamarca isolate from Peru, resistant to both
      triclabendazole and albendazole (TCBZR/ABZR) and the Rubino isolate from Uruguay,
      resistant to ABZ (TCBZS/ABZR), and compare them to a sensitive strain (Cenapa,
      Mexico, TCBZS/ABZS) to reveal putative molecular mechanisms leading to drug
      resistance. RESULTS: We observed a major reduction in transcription in the
      Cajamarca TCBZR/ABZR isolate in comparison to the other isolates. While most of
      the differentially expressed genes are still unannotated, several trends could be
      detected. Specific reduction in the expression levels of cytoskeleton proteins
      was consistent with a role of tubulins as putative targets of triclabendazole
      (TCBZ). A marked reduction of adenylate cyclase might be underlying pleiotropic
      effects on diverse metabolic pathways of the parasite. Upregulation of GST mu
      isoforms suggests this detoxifying mechanism as one of the strategies associated
      with resistance. CONCLUSIONS: Our results stress the value of transcriptomic
      approaches as a means of providing novel insights to advance the understanding of
      drug mode of action and drug resistance. The results provide evidence for
      pleiotropic variations in drug-resistant isolates consistent with early
      observations of TCBZ and ABZ effects and recent proteomic findings.

PMID- 29368660
TI  - Incidental findings in CT imaging of coronary artery bypass grafts: results from
      a Canadian multicenter prospective cohort.
AB  - OBJECTIVE: To assess the prevalence and clinical significance of incidental
      findings identified during computed tomography imaging of coronary artery bypass
      grafts. RESULTS: This prospective study includes 144 patients undergoing coronary
      graft patency assessment using computed tomography. Incidental findings were
      classified as significant if they were considered to need an immediate action or
      treatment, short-term work-up or follow-up, or minor. A total of 211 incidental
      findings were present in 109 (75.7%) patients. Seventy-one incidental findings
      (33.6%) were cardiac and 140 (66.4%) were extracardiac. Most common cardiac
      incidental findings were atrial dilatation [39 patients, 48 incidental findings
      (67.6%)] and aortic valve calcifications (7 patients, 9.9%). Among the 140
      extracardiac incidental findings, the most common were lung nodules (51 patients,
      54 nodules, 38.6%), and emphysema (21 patients, 15%). Thirty-six (25.7%)
      extracardiac incidental findings were significant and notably, 23 (63.9%) were
      lung nodules. Follow-up was recommended in 37 cases, among which all patients
      with significant lung nodules (23 patients, 62.2%). In conclusion, most common
      computed tomography incidental findings in patients with coronary grafts were
      lung nodules and emphysema.

PMID- 29368661
TI  - Effective practices of international volunteering for health: perspectives from
      partner organizations.
AB  - BACKGROUND: The demand for international volunteer experiences to promote global
      health and nutrition is increasing and numerous studies have documented the
      experiences of the international volunteers who travel abroad; however, little is
      known about effective practices from the perspective of partner organizations.
      This study aims to understand how variables such as the skill-level of
      volunteers, the duration of service, cultural and language training, and other
      key variables affect partner organizations' perceptions of volunteer
      effectiveness at promoting healthcare and nutrition. METHOD: This study used a
      cross-sectional design to survey a convenience sample of 288 volunteer partner
      organizations located in 68 countries. Principle components analyses and manual
      coding of cases resulted in a categorization of five generalized types of
      international volunteering. Differences among these types were compared by the
      duration of service, skill-level of volunteers, and the volunteers' perceived fit
      with organizational needs. In addition, a multivariate ordinary least square
      regression tested associations between nine different characteristics/activities
      and the volunteers' perceived effectiveness at promoting healthcare and
      nutrition. RESULTS: Partner organizations viewed highly-skilled volunteers
      serving for a short-term abroad as the most effective at promoting healthcare and
      nutrition in their organizations, followed by slightly less-skilled long-term
      volunteers. The greatest amount of variance in perceived effectiveness was
      volunteers' ability to speak the local language, followed by their skill level
      and the duration of service abroad. In addition, volunteer training in community
      development principles and practices was significantly related to perceived
      effectiveness. CONCLUSION: The perceptions of effective healthcare promotion
      identified by partner organizations suggest that program and volunteer
      characteristics need to be carefully considered when deciding on methods of
      volunteer preparation and engagement. By better integrating evidence-based
      practices into their program models, international volunteer cooperation
      organizations can greatly strengthen their efforts to promote more effective and
      valuable healthcare and nutrition interventions in partner communities.

PMID- 29368662
TI  - Treatment outcomes in patients with opioid use disorder initiated by
      prescription: a systematic review protocol.
AB  - BACKGROUND: In North America, opioid use has become a public health crisis with
      policy makers declaring it a state of emergency. Opioid substitution therapy
      (OST) is a harm-reduction method used in treating opioid use disorder. While OST
      has shown to be successful in improving treatment outcomes, there is still a
      great degree of variability among patients. This cohort of patients has shifted
      from young males using heroin to a greater number of older people and women using
      prescription opioids. The primary objective of this review is to examine the
      literature on the association between the first exposure to opioids through
      prescription versus illicit use and OST treatment outcomes. METHOD: An electronic
      search will be conducted on the EMBASE, MEDLINE, PsycINFO, and Cumulative Index
      to Nursing and Allied Health Literature (CINAHL) databases. Two independent
      reviewers will conduct the initial title and abstract screenings using
      predetermined criteria for inclusion and exclusion. Reviewers will then conduct
      full-text data extraction using a pilot-tested data extraction form in duplicate.
      A third author will resolve disagreements if consensus cannot be reached. Quality
      and risk of bias assessment will be conducted along with a sensitivity analysis
      for all included studies. Qualitative summary of the evidence will be provided,
      and when possible, a meta-analysis will be conducted, along with heterogeneity
      calculation. The reporting of this protocol follows the PRISMA-P. DISCUSSION: We
      expect that this review will help determine whether patients that were initially
      exposed to opioids through a prescription differ in OST treatment outcomes in
      comparison to people who used opioids through illicit means. We hope that this
      review will provide evidence related to prescription opioids exposure and future
      treatment outcomes, which will aid clinicians in their decisions to prescribe
      opioids or not for specific populations at risk. SYSTEMATIC REVIEW REGISTRATION:
      PROSPERO CRD42017058143.

PMID- 29368663
TI  - Developmental dynamics of gene expression and alternative polyadenylation in the
      Caenorhabditis elegans germline.
AB  - BACKGROUND: The 3' untranslated regions (UTRs) of mRNAs play a major role in post
      transcriptional regulation of gene expression. Selection of transcript cleavage
      and polyadenylation sites is a dynamic process that produces multiple transcript
      isoforms for the same gene within and across different cell types. Using LITE
      Seq, a new quantitative method to capture transcript 3' ends expressed in vivo,
      we have characterized sex- and cell type-specific transcriptome-wide changes in
      gene expression and 3'UTR diversity in Caenorhabditis elegans germline cells
      undergoing proliferation and differentiation. RESULTS: We show that nearly half
      of germline transcripts are alternatively polyadenylated, that differential
      regulation of endogenous 3'UTR variants is common, and that alternative isoforms
      direct distinct spatiotemporal protein expression patterns in vivo. Dynamic
      expression profiling also reveals temporal regulation of X-linked gene
      expression, selective stabilization of transcripts, and strong evidence for a
      novel developmental program that promotes nucleolar dissolution in oocytes. We
      show that the RNA-binding protein NCL-1/Brat is a posttranscriptional regulator
      of numerous ribosome-related transcripts that acts through specific U-rich
      binding motifs to down-regulate mRNAs encoding ribosomal protein subunits, rRNA
      processing factors, and tRNA synthetases. CONCLUSIONS: These results highlight
      the pervasive nature and functional potential of patterned gene and isoform
      expression during early animal development.

PMID- 29368665
TI  - Dismantling cognitive-behaviour therapy for panic disorder: a systematic review
      and component network meta-analysis.
AB  - Cognitive-behaviour therapy (CBT) for panic disorder may consist of different
      combinations of several therapeutic components such as relaxation, breathing
      retraining, cognitive restructuring, interoceptive exposure and/or in vivo
      exposure. It is therefore important both theoretically and clinically to examine
      whether specific components of CBT or their combinations are superior to others
      in the treatment of panic disorder. Component network meta-analysis (NMA) is an
      extension of standard NMA that can be used to disentangle the treatment effects
      of different components included in composite interventions. We searched MEDLINE,
      EMBASE, PsycINFO and Cochrane Central, with supplementary searches of reference
      lists and clinical trial registries, for all randomized controlled trials
      comparing different CBT-based psychological therapies for panic disorder with
      each other or with control interventions. We applied component NMA to disentangle
      the treatment effects of different components included in these interventions.
      After reviewing 2526 references, we included 72 studies with 4064 participants.
      Interoceptive exposure and face-to-face setting were associated with better
      treatment efficacy and acceptability. Muscle relaxation and virtual-reality
      exposure were associated with significantly lower efficacy. Components such as
      breathing retraining and in vivo exposure appeared to improve treatment
      acceptability while having small effects on efficacy. The comparison of the most
      v. the least efficacious combination, both of which may be provided as 'evidence
      based CBT,' yielded an odds ratio for the remission of 7.69 (95% credible
      interval: 1.75 to 33.33). Effective CBT packages for panic disorder would include
      face-to-face and interoceptive exposure components, while excluding muscle
      relaxation and virtual-reality exposure.

PMID- 29368664
TI  - Extensive epigenetic reprogramming during the life cycle of Marchantia
      polymorpha.
AB  - BACKGROUND: In plants, the existence and possible role of epigenetic
      reprogramming has been questioned because of the occurrence of stably inherited
      epialleles. Evidence suggests that epigenetic reprogramming does occur during
      land plant reproduction, but there is little consensus on the generality and
      extent of epigenetic reprogramming in plants. We studied DNA methylation dynamics
      during the life cycle of the liverwort Marchantia polymorpha. We isolated thalli
      and meristems from male and female gametophytes, archegonia, antherozoids, as
      well as sporophytes at early and late developmental stages, and compared their
      DNA methylation profiles. RESULTS: Of all cytosines tested for differential DNA
      methylation, 42% vary significantly in their methylation pattern throughout the
      life cycle. However, the differences are limited to few comparisons between
      specific stages of the life cycle and suggest four major epigenetic states
      specific to sporophytes, vegetative gametophytes, antherozoids, and archegonia.
      Further analyses indicated clear differences in the mechanisms underlying
      reprogramming in the gametophytic and sporophytic generations, which are
      paralleled by differences in the expression of genes involved in DNA methylation.
      Differentially methylated cytosines with a gain in methylation in antherozoids
      and archegonia are enriched in the CG and CHG contexts, as well as in gene bodies
      and gene flanking regions. In contrast, gain of DNA methylation during sporophyte
      development is mostly limited to the CHH context, LTR retrotransposons, DNA
      transposons, and repeats. CONCLUSION: We conclude that epigenetic reprogramming
      occurs at least twice during the life cycle of M. polymorpha and that the
      underlying mechanisms are likely different between the two events.

PMID- 29368666
TI  - Tryptophan supplementation and serotonin function: genetic variations in
      behavioural effects.
AB  - The neurotransmitter serotonin has a role in affective disorders such as
      depression and anxiety, as well as sleep, cognitive function and appetite. This
      review examines the evidence that serotonin-related genotypes may moderate the
      behavioural effects of supplementation with the serotonin precursor amino acid l
      tryptophan (TRP), on which synthesis of serotonin (or 5-hydroxytryptamine; 5-HT)
      depends. However, 95 % of serotonin is synthesised and used in the periphery, and
      TRP is also metabolised via non-5-HT routes such as the kynurenine pathway.
      Moreover, understanding of genotypes involved in regulation of serotonin raises
      questions over the generalisability of TRP effects on behaviour across
      individuals with varied serotonergic genotypes. To date, only differences between
      variants of the 5-HT transporter-linked promoter region (5-HTTLPR) have been
      investigated in relation to behavioural effects of TRP supplementation. Effects
      of 5-HTTLPR genotypes are usually compared between the alleles that are either
      high (L/L') or low (S/S') expressing of mRNA for the 5-HT transporter receptor.
      Yet, another key genetic variable is sex: in women, the S/S' genotype predicts
      sensitivity to improved mood and reduced cortisol by TRP supplementation, during
      stressful challenges, whereas the L/L' genotype protects against stress-induced
      mood deterioration. In men, the L/L' genotype may confer risk of stress-induced
      increases in negative affect; there are insufficient data to assess effects on
      male S/S' genotypes. However, better-powered studies to detect sex by genotype by
      stress by TRP interactions, as well as consideration of more genotypes, are
      needed before strong conclusions and recommendations for behavioural effects of
      TRP treatment can be reached.

PMID- 29368667
TI  - Hypervirulent Clostridium difficile Strain Has Arrived in Brazil.

PMID- 29368668
TI  - The death of expertise (in medicine).

PMID- 29368669
TI  - [La disparition de l'expertise (en medecine)].

PMID- 29368670
TI  - A solution to gender inequity in surgery? Better caregiving policies.
AB  - SUMMARY: Attitudes toward women in surgery appear to be shifting in a positive
      direction. Why, then, do women still represent only 27% of surgeons in Canada?
      The answer may, at least in part, lie in the field's inability to adequately
      accommodate caregiving duties, which are still disproportionately "women's
      responsibilities" in our society. Although most Canadian academic centres now
      have paid maternity leave policies for trainees and faculty, these do not
      necessarily apply to surgeons working in the community, nor do they always
      reflect what occurs in practice. The perceived inability of the field to
      accommodate both personal and professional duties is often a significant
      deterrent to young women considering a career in surgery. In this commentary, we
      explore the need to address the "caregiver problem" as an important step toward
      achieving gender equity in surgery.

PMID- 29368671
TI  - No. 3 Canadian General Hospital (McGill) in the Great War: service and sacrifice.
AB  - SUMMARY: During the Great War, McGill University fielded a full general hospital
      to care for the wounded and sick among the Allied forces fighting in France and
      Belgium. The unit was designated No. 3 Canadian General Hospital (McGill) and
      included some of the best medical minds in Canada. Because the unit had a
      relationship with Sir William Osler, who was a professor at McGill from 1874 to
      1885, the unit received special attention throughout the war, and legendary
      Canadian medical figures, such as John McCrae, Edward Archibald and Francis
      Scrimger, VC, served on its staff. The unit cared for thousands of victims of the
      war, and its trauma care advanced through the clinical innovation and research
      demanded by the nature of its work. Although No. 3 Canadian General Hospital
      suffered tragedies as well, such as the deaths of John McCrae and Osler's only
      son Revere, by the war's end the McGill hospital was known as one of the best
      medical units within the armies in France.

PMID- 29368672
TI  - Process mapping as a framework for performance improvement in emergency general
      surgery.
AB  - BACKGROUND: Emergency general surgery conditions are often thought of as being
      too acute for the development of standardized approaches to quality improvement.
      However, process mapping, a concept that has been applied extensively in
      manufacturing quality improvement, is now being used in health care. The
      objective of this study was to create process maps for small bowel obstruction in
      an effort to identify potential areas for quality improvement. METHODS: We used
      the American College of Surgeons Emergency General Surgery Quality Improvement
      Program pilot database to identify patients who received nonoperative or
      operative management of small bowel obstruction between March 2015 and March
      2016. This database, patient charts and electronic health records were used to
      create process maps from the time of presentation to discharge. RESULTS: Eighty
      eight patients with small bowel obstruction (33 operative; 55 nonoperative) were
      identified. Patients who received surgery had a complication rate of 32%. The
      processes of care from the time of presentation to the time of follow-up were
      highly elaborate and variable in terms of duration; however, the sequences of
      care were found to be consistent. We used data visualization strategies to
      identify bottlenecks in care, and they showed substantial variability in terms of
      operating room access. CONCLUSION: Variability in the operative care of small
      bowel obstruction is high and represents an important improvement opportunity in
      general surgery. Process mapping can identify common themes, even in acute care,
      and suggest specific performance improvement measures.

PMID- 29368673
TI  - Analysis of postdischarge costs following emergent general surgery in elderly
      patients.
AB  - BACKGROUND: As populations age, more elderly patients will undergo surgery.
      Frailty and complications are considered to increase in-hospital cost in older
      adults, but little is known on costs following discharge, particularly those
      borne by the patient. We examined risk factors for increased cost and the type of
      costs accrued following discharge in elderly surgical patients. METHODS: Acute
      abdominal surgery patients aged 65 years and older were prospectively enrolled.
      We assessed baseline clinical characteristics, including Clinical Frailty Scale
      (CFS) scores. We calculated 6-month cost (in Canadian dollars) from patient
      reported use following discharge according to the validated Health Resource
      Utilization Inventory. Primary outcomes were 6-month overall cost and cost for
      health care services, medical products and lost productive hours. Outcomes were
      log-transformed and assessed in multivariable generalized linear and zero
      inflated negative binomial regressions and can be interpreted as adjusted ratios
      (AR). Complications were assessed according to Clavien-Dindo classification.
      RESULTS: We included 150 patients (mean age 75.5 +/- 7.6 yr; 54.1% men) in our
      analysis; 10.8% had major and 43.2% had minor complications postoperatively. The
      median 6-month overall cost was $496 (interquartile range $140-$1948).
      Disaggregated by cost type, frailty independently predicted increasing costs of
      health care services (AR 1.76, 95% confidence interval [CI] 1.43-2.18, p < 0.001)
      and medical products (AR 1.61, 95% CI 1.15-2.25, p = 0.005), but decreasing costs
      in lost productive hours (AR 0.39, p = 0.002). Complications did not predict
      increased cost. CONCLUSION: Frail patients accrued higher health care services
      and product costs, but lower costs from lost productive hours. Interventions in
      elderly surgical patients should consider patient-borne cost in older adults and
      lost productivity in less frail patients. TRIAL REGISTRATION: NCT02233153
      (clinicaltrials.gov).

PMID- 29368674
TI  - Effect of patient decision aid was influenced by presurgical evaluation among
      patients with osteoarthritis of the knee.
AB  - BACKGROUND: Decision aids help patients make total joint arthroplasty decisions,
      but presurgical evaluation might influence the effects of a decision aid. We
      compared the effects of a decision aid among patients considering total knee
      arthroplasty at 2 surgical screening clinics with different evaluation processes.
      METHODS: We performed a subgroup analysis of a randomized controlled trial.
      Patients were recruited from 2 surgical screening clinics: an academic clinic
      providing 20-minute physician consultations and a community clinic providing 45
      minute physiotherapist/nurse consultations with education. We compared the
      effects of decision quality, decisional conflict and surgery rate using Cochran
      Mantel-Haenszel chi2 tests and the Breslow-Day test. RESULTS: We evaluated 242
      patients: 123 from the academic clinic (61 who used the decision aid and 62
      controls) and 119 from the community clinic (59 who used the decision aid and 60
      controls). Results suggested a between-site difference in the effect of the
      decision aid on the patients' decision quality (p = 0.09): at the academic site,
      patients who used the decision aid were more likely to make better-quality
      decisions than controls (54% v. 35%, p = 0.044), but not at the community site
      (47% v. 51%, p = 0.71). Fewer patients who used decision aids at the academic
      site than at the community site experienced decisional conflict (p = 0.007) (33%
      v. 52%, p = 0.05 at the academic site and 40% v. 24%, p = 0.08 at the community
      site). The effect of the decision aid on surgery rates did not differ between
      sites (p = 0.65). CONCLUSION: The decision aid had a greater effect at the
      academic site than at the community site, which provided longer consultations
      with more verbal education. Hence, decision aids might be of greater value when
      more extensive total knee arthroplasty presurgical assessment and counselling are
      either impractical or unavailable.

PMID- 29368675
TI  - Tertiary care centre adherence to unified guidelines for management of
      periprosthetic joint infections: a gap analysis.
AB  - BACKGROUND: The success rate of surgical treatment for periprosthetic joint
      infection (PJI) remains inconsistent in the literature. Variability in PJI
      clinical guidelines and surgeon adherence to guidelines could affect treatment
      success. The objectives of this study were to appraise current recommendations
      for PJI management and develop a unified clinical standard of care, to perform a
      gap analysis of PJI cases in a tertiary institution to determine the rate of
      guideline adherence, and to determine if adherence to unified PJI guidelines
      affected 2-year treatment outcomes. METHODS: We appraised the PJI guidelines from
      3 academic medical societies, and consistent statements were aggregated. We
      retrospectively reviewed all PJI cases in a tertiary care institution. We defined
      PJI based on Musculoskeletal Infection Society PJI criteria. Surgeon adherence to
      preoperative, intraoperative, surgical and medical management guidelines was
      calculated, and we evaluated the association between guideline adherence and 2
      year treatment outcomes. RESULTS: The institutional rate of PJI was 1.13% (38 of
      3368). Treatment success was 57.8% at 2 years. Unified guideline adherence
      percentages varied substantially: 92% of patients had preoperative erythrocyte
      sedimentation rate and C-reactive protein, 97% had intraoperative tissue
      cultures, 42% had appropriate preoperative arthrocentesis, and 74% underwent
      guideline-appropriate surgery. Performing appropriate preoperative arthrocentesis
      significantly correlated with positive treatment outcomes at 2 years (p = 0.028).
      CONCLUSION: Adherence to PJI guidelines varies considerably, indicating that
      clinicians are either unaware of them or do not recognize their value for PJI
      treatment. This study shows the need for institution-based PJI treatment pathways
      that are consistent with published guidelines and the need to monitor adherence.

PMID- 29368676
TI  - Physical performance following acute high-risk abdominal surgery: a prospective
      cohort study.
AB  - BACKGROUND: Acute high-risk abdominal (AHA) surgery is associated with high
      mortality, multiple postoperative complications and prolonged hospital stay.
      Further development of strategies for enhanced recovery programs following AHA
      surgery is needed. The aim of this study was to describe physical performance and
      barriers to independent mobilization among patients who received AHA surgery
      (postoperative days [POD] 1-7). METHODS: Patients undergoing AHA surgery were
      consecutively enrolled from a university hospital in Denmark. In the first
      postoperative week, all patients were evaluated daily with regards to physical
      performance, using the Cumulated Ambulation Score (CAS; 0-6 points) to assess
      basic mobility and the activPAL monitor to assess the 24-hour physical activity
      level. We recorded barriers to independent mobilization. RESULTS: Fifty patients
      undergoing AHA surgery (mean age 61.4 +/- 17.2 years) were included. Seven
      patients died within the first postoperative week, and 15 of 43 (35%) patients
      were still not independently mobilized (CAS < 6) on POD-7, which was associated
      with pulmonary complications developing (53% v. 14% in those with CAS = 6, p =
      0.012). The patients lay or sat for a median of 23.4 hours daily during the first
      week after AHA surgery, and the main barriers to independent mobilization were
      fatigue and abdominal pain. CONCLUSION: Patients who receive AHA surgery have
      very limited physical performance in the first postoperative week. Barriers to
      independent mobilization are primarily fatigue and abdominal pain. Further
      studies investigating strategies for early mobilization and barriers to
      mobilization in the immediate postoperative period after AHA surgery are needed.

PMID- 29368677
TI  - Comparing the anterior, posterior and lateral approach: gait analysis in total
      hip arthroplasty.
AB  - BACKGROUND: The choice of surgical approach for total hip arthroplasty (THA)
      remains a contentious issue with regards to clinical outcome optimization and
      restoring patient function. The purpose of this study was to determine the impact
      of surgical approach for THA on quantitative gait analysis. METHODS: Patients
      undergoing THA for primary osteoarthritis of the hip were assigned to 1 of 3
      surgical approaches: anterior, posterior and lateral. Standardized implants were
      used at the time of surgery. Three-dimensional gait analysis was performed
      preoperatively and at 6 and 12 weeks postoperatively. At each time point, we
      compared temporal parameters, kinematics and kinetics. RESULTS: We included 30
      patients in our analysis (10 anterior, 10 posterior, and 10 lateral). The groups
      were similar with respect to age (p = 0.27), body mass index (p = 0.16), and
      Charlson Comorbidity Index score (p = 0.66). Temporal parameters were similar
      among the groups at all time points. The lateral cohort had higher pelvic tilt
      during stance on the affected leg than the anterior cohort at 6 weeks (p =
      0.041). Affected leg ipsilateral trunk lean during stance was higher in the
      lateral group than in the other cohorts at 6 weeks (p = 0.008) and 12 weeks (p =
      0.040). The anterior and posterior groups showed increased external rotation at 6
      weeks (p = 0.003) and 12 weeks (p = 0.012) compared with the lateral group.
      CONCLUSION: Temporal gait parameters were similar following THA for all
      approaches. Differences in gait kinematics and kinetics exist; however, given the
      small absolute differences, the clinical importance of these changes remains
      undetermined.

PMID- 29368679
TI  - Can surgical site infections be reduced with the adoption of a bundle of
      simultaneous initiatives? The use of NSQIP incidence data to follow multiple
      quality improvement interventions.
AB  - SUMMARY: Surgical site infections (SSI) are a common complication after surgical
      procedures. To reduce the incidence of SSIs, Oakville Trafalgar Memorial Hospital
      decided to institute a bundle of initiatives to change multiple factors
      simultaneously based on best available evidence and the understanding of
      infection pathophysiology. We used National Surgical Quality Improvement Program
      data on the incidence of SSIs in our targeted and essentials, general surgery and
      orthopedic surgery cases before and after the implementation of an SSI reduction
      bundle. This article discusses whether the use of intervention bundles may assist
      in the reduction of a variety of postoperative surgical complications.

PMID- 29368680
TI  - Intraoperative ultrasonic cholangiography for biliary system identification.

PMID- 29368681
TI  - Author response to: Intraoperative ultrasonic cholangiography for biliary system
      identification.

PMID- 29368678
TI  - A systematic review of the factors affecting choice of surgery as a career.
AB  - BACKGROUND: Interest in surgical careers among medical students has declined over
      the past decade. Multiple explanations have been offered for why top students are
      deterred or rejected from surgical programs, though no consensus has emerged.
      METHODS: We conducted a review of the literature to better characterize what
      factors affect the pursuit of a surgical career. We searched PubMed and EMBASE
      and performed additional reference checks. Agency for Healthcare Research and
      Quality (AHRQ) and Newcastle-Ottawa Education scores were used to evaluate the
      included data. RESULTS: Our search identified 122 full-text, primary articles.
      Analysis of this evidence identified 3 core concepts that impact surgical career
      decision-making: gender, features of surgical education, and student "fit" in the
      culture of surgery. CONCLUSION: Real and perceived gender discrimination has
      deterred female medical students from entering surgical careers. In addition,
      limited exposure to surgery during medical school and differences between student
      and surgeon personality traits and values may deter students from entering
      surgical careers. We suggest that deliberate and visible effort to include women
      and early-career medical students in surgical settings may enhance their interest
      in carreers in surgery.

PMID- 29368682
TI  - Correction of place of practice: Brampton, not Brantford.

PMID- 29368683
TI  - Author response to: Correction of place of practice: Brampton, not Brantford.

PMID- 29368684
TI  - ?

PMID- 29368685
TI  - [Masked hypertension during pregnancy].
AB  - Hypertension during pregnancy is one of the leading causes of maternal and foetal
      morbidity and mortality. Monitoring of blood pressure is therefore an essential
      part of prenatal care. Masked hypertension, where blood pressure levels are
      elevated at home despite normal blood pressure levels monitored in a clinical
      setting, may lead to cardiovascular and obstetric complications equal to those of
      sustained hypertension. This article discusses masked hypertension and the need
      for further investigation of blood pressure monitoring during pregnancy.

PMID- 29368686
TI  - [Surgical treatment of lumbar disc herniation].
AB  - The Danish Health Authority has recently published a new guideline on the
      treatment of lumbar disc herniation with radiculopathy. This paper goes through
      the surgical treatment and considers the evidence behind surgical treatment of
      these patients, along with the outcome reported in literature. The new guideline
      recommends referring patients to be assessed by a surgeon within 12 weeks in
      cases, where severe and debilitating pain persists despite non-surgical
      treatment. This is found to be well in line with literature, as many studies have
      shown time to be a predictive factor in surgical treatment of these patients.

PMID- 29368687
TI  - [Meningitis and septic sinus thrombosis in connection with otitis media].
AB  - This is a case report of a 30-year-old female, who presented to the emergency
      department with headache, nausea and neck pain after five days of otitis media.
      After lumbar puncture, CT and MRI the patient was treated for meningitis with
      initial improvement in the clinical state. After four days she developed
      contralateral neurological symptoms, and after five days she had a seizure. MR
      venography showed thrombosis of the lateral dural sinus with venous cerebral
      infarction. The treatment of intravenously administered antibiotics,
      mastoidectomy and anticoagulation is discussed and compared with other cases in
      the literature.

PMID- 29368688
TI  - [Comorbidity in connection with psoriasis is more than psoriatic arthritis].
AB  - Psoriasis is a common chronic inflammatory disease which is associated with
      extensive comorbidity, including psoriatic arthritis, cardiovascular and
      cardiometabolic disease, inflammatory bowel disease, malignancy, chronic kidney
      disease and depression. Clinical guidelines have been developed to target some of
      these comorbid diseases in patients with psoriasis and should be used by the
      treating physician.

PMID- 29368689
TI  - [Melioidosis is a rare diagnosis among returning travellers with fever].
AB  - The causative organism of melioidosis is Burkholderia pseudomallei, a Gram
      negative bacterium endemic to Southeast Asia and Northern Australia. The clinical
      presentation varies, ranging from asymptomatic cases to rapidly progressive
      septicaemia and shock. Abscesses may be found in any internal organ. We describe
      an infrequent presentation of melioidosis with various symptoms, including
      haematuria and rectal pain. Perirectal and prostatic abscesses were found, the
      causative organism was identified and relevant treatment administered, resulting
      in a full recovery.

PMID- 29368692
TI  - Theoretical prediction of sandwiched two-dimensional phosphide binary compound
      sheets with tunable bandgaps and anisotropic physical properties.
AB  - Atomic layers of GaP and InP binary compounds with unique anisotropic structural,
      electronic and mechanical properties have been predicted from first-principle
      molecular dynamics simulations. These new members of the phosphide binary
      compound family stabilize to a sandwiched two-dimensional (2D) crystalline
      structure with orthorhombic lattice symmetry and high buckling of 2.14 A-2.46 A.
      Their vibration modes are similar to those of phosphorene with six Raman active
      modes ranging from ~80 cm-1 to 400 cm-1. The speeds of sound in their phonon
      dispersions reflect anisotropy in their elastic constants, which was further
      confirmed by their strong directional dependence of Young's moduli and effective
      nonlinear elastic moduli. They show wide bandgap semiconductor behavior with
      fundamental bandgaps of 2.89 eV for GaP and 2.59 eV for InP, respectively, even
      wider than their bulk counterparts. Such bandgaps were found to be tunable under
      strain. In particular, a direct-indirect bandgap transition was found under
      certain strains along zigzag or biaxial orientations, reflecting their promising
      applications in strain-induced bandgap engineering in nanoelectronics and
      photovoltaics. Feasible pathways to realize these novel 2D phosphide compounds
      are also proposed.

PMID- 29368691
TI  - Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling
      hub.
AB  - Infection and tissue damage induces assembly of supramolecular organizing centres
      (SMOCs)), such as the Toll-like receptor (TLR) MyDDosome, to co-ordinate
      inflammatory signaling. SMOC assembly is thought to drive digital all-or-none
      responses, yet TLR activation by diverse microbes induces anything from mild to
      severe inflammation. Using single-molecule imaging of TLR4-MyDDosome signaling in
      living macrophages, we find that MyDDosomes assemble within minutes of TLR4
      stimulation. TLR4/MD2 activation leads only to formation of TLR4/MD2
      heterotetramers, but not oligomers, suggesting a stoichiometric mismatch between
      activated receptors and MyDDosomes. The strength of TLR4 signalling depends not
      only on the number and size of MyDDosomes formed but also how quickly these
      structures assemble. Activated TLR4, therefore, acts transiently nucleating
      assembly of MyDDosomes, a process that is uncoupled from receptor activation.
      These data explain how the oncogenic mutation of MyD88 (L265P) assembles
      MyDDosomes in the absence of receptor activation to cause constitutive activation
      of pro-survival NF-kappaB signalling.

PMID- 29368693
TI  - Surface-screening mechanisms in ferroelectric thin films and their effect on
      polarization dynamics and domain structures.
AB  - For over 70 years, ferroelectric materials have been one of the central research
      topics for condensed matter physics and material science, an interest driven both
      by fundamental science and applications. However, ferroelectric surfaces, the key
      component of ferroelectric films and nanostructures, still present a significant
      theoretical and even conceptual challenge. Indeed, stability of ferroelectric
      phase per se necessitates screening of polarization charge. At surfaces, this can
      lead to coupling between ferroelectric and semiconducting properties of material,
      or with surface (electro) chemistry, going well beyond classical models
      applicable for ferroelectric interfaces. In this review, we summarize recent
      studies of surface-screening phenomena in ferroelectrics. We provide a brief
      overview of the historical understanding of the physics of ferroelectric
      surfaces, and existing theoretical models that both introduce screening
      mechanisms and explore the relationship between screening and relevant aspects of
      ferroelectric functionalities starting from phase stability itself. Given that
      the majority of ferroelectrics exist in multiple-domain states, we focus on local
      studies of screening phenomena using scanning probe microscopy techniques. We
      discuss recent studies of static and dynamic phenomena on ferroelectric surfaces,
      as well as phenomena observed under lateral transport, light, chemical, and
      pressure stimuli. We also note that the need for ionic screening renders
      polarization switching a coupled physical-electrochemical process and discuss the
      non-trivial phenomena such as chaotic behavior during domain switching that stem
      from this.

PMID- 29368690
TI  - BAD and KATP channels regulate neuron excitability and epileptiform activity.
AB  - Brain metabolism can profoundly influence neuronal excitability. Mice with
      genetic deletion or alteration of Bad (BCL-2 agonist of cell death) exhibit
      altered brain-cell fuel metabolism, accompanied by resistance to acutely induced
      epileptic seizures; this seizure protection is mediated by ATP-sensitive
      potassium (KATP) channels. Here we investigated the effect of BAD manipulation on
      KATP channel activity and excitability in acute brain slices. We found that BAD's
      influence on neuronal KATP channels was cell-autonomous and directly affected
      dentate granule neuron (DGN) excitability. To investigate the role of neuronal
      KATP channels in the anticonvulsant effects of BAD, we imaged calcium during
      picrotoxin-induced epileptiform activity in entorhinal-hippocampal slices. BAD
      knockout reduced epileptiform activity, and this effect was lost upon knockout or
      pharmacological inhibition of KATP channels. Targeted BAD knockout in DGNs alone
      was sufficient for the antiseizure effect in slices, consistent with a 'dentate
      gate' function that is reinforced by increased KATP channel activity.

PMID- 29368695
TI  - Polymers and biopolymers at interfaces.
AB  - This review updates recent progress in the understanding of the behaviour of
      polymers at surfaces and interfaces, highlighting examples in the areas of
      wetting, dewetting, crystallization, and 'smart' materials. Recent developments
      in analysis tools have yielded a large increase in the study of biological
      systems, and some of these will also be discussed, focussing on areas where
      surfaces are important. These areas include molecular binding events and protein
      adsorption as well as the mapping of the surfaces of cells. Important techniques
      commonly used for the analysis of surfaces and interfaces are discussed
      separately to aid the understanding of their application.

PMID- 29368694
TI  - Quantum plasmon and Rashba-like spin splitting in self-assembled Co x C60
      composites with enhanced Co content (x > 15).
AB  - Driving by interplay between plasmonic and magnetic effects in organic composite
      semiconductors is a challenging task with a huge potential for practical
      applications. Here, we present evidence of a quantum plasmon excited in the self
      assembled Co x C60 nanocomposite films with x > 15 (interval of the Co cluster
      coalescence) and analyse it using the optical absorption (OA) spectra. In the
      case of Co x C60 film with x = 16 (LF sample), the quantum plasmon generated by
      the Co/CoO clusters is found as the 1.5 eV-centred OA peak. This finding is
      supported by the establishment of four specific C60-related OA lines detected at
      the photon energies E p  > 2.5 eV. Increase of the Co content up to x = 29 (HF
      sample) leads to pronounced enhancement of OA intensity in the energy range of E
      p  > 2.5 eV and to plasmonic peak downshift of 0.2 eV with respect to the peak
      position in the LF spectrum. Four pairs of the OA peaks evaluated in the HF
      spectrum at E p  > 2.5 eV reflect splitting of the C60-related lines, suggesting
      great change in the microscopic conditions with increasing x. Analysis of the
      film nanostructure and the plasmon-induced conditions allows us to propose a
      Rashba-like spin splitting effect that suggests valuable sources for spin
      polarization.

PMID- 29368696
TI  - Guggulsterone-releasing microspheres direct the differentiation of human induced
      pluripotent stem cells into neural phenotypes.
AB  - Parkinson's disease (PD), a common neurodegenerative disorder, results from the
      loss of motor function when dopaminergic neurons (DNs) in the brain selectively
      degenerate. While pluripotent stem cells (PSCs) show promise for generating
      replacement neurons, current protocols for generating terminally differentiated
      DNs require a complicated cocktail of factors. Recent work demonstrated that a
      naturally occurring steroid called guggulsterone effectively differentiated PSCs
      into DNs, simplifying this process. In this study, we encapsulated guggulsterone
      into novel poly-epsilon-caprolactone-based microspheres and characterized its
      release profile over 44 d in vitro, demonstrating we can control its release over
      time. These guggulsterone-releasing microspheres were also successfully
      incorporated in human induced pluripotent stem cell-derived cellular aggregates
      under feeder-free and xeno-free conditions and cultured for 20 d to determine
      their effect on differentiation. All cultures stained positive for the early
      neuronal marker TUJ1 and guggulsterone microsphere-incorporated aggregates did
      not adversely affect neurite length and branching. Guggulsterone microsphere
      incorporated aggregates exhibited the highest levels of TUJ1 expression as well
      as high Olig 2 expression, an inhibitor of the STAT3 astrogenesis pathway
      previously known as a target for guggulsterone in cancer treatment. Together,
      this study represents an important first step towards engineered neural tissues
      consisting of guggulsterone microspheres and PSCs for generating DNs that could
      eventually be evaluated in a pre-clinical model of PD.

PMID- 29368697
TI  - How do reference montage and electrodes setup affect the measured scalp EEG
      potentials?
AB  - OBJECTIVE: Human scalp electroencephalogram (EEG) is widely applied in cognitive
      neuroscience and clinical studies due to its non-invasiveness and ultra-high time
      resolution. However, the representativeness of the measured EEG potentials for
      the underneath neural activities is still a problem under debate. This study aims
      to investigate systematically how both reference montage and electrodes setup
      affect the accuracy of EEG potentials. APPROACH: First, the standard EEG
      potentials are generated by the forward calculation with a single dipole in the
      neural source space, for eleven channel numbers (10, 16, 21, 32, 64, 85, 96, 128,
      129, 257, 335). Here, the reference is the ideal infinity implicitly determined
      by forward theory. Then, the standard EEG potentials are transformed to
      recordings with different references including five mono-polar references (Left
      earlobe, Fz, Pz, Oz, Cz), and three re-references (linked mastoids (LM), average
      reference (AR) and reference electrode standardization technique (REST)).
      Finally, the relative errors between the standard EEG potentials and the
      transformed ones are evaluated in terms of channel number, scalp regions,
      electrodes layout, dipole source position and orientation, as well as sensor
      noise and head model. MAIN RESULTS: Mono-polar reference recordings are usually
      of large distortions; thus, a re-reference after online mono-polar recording
      should be adopted in general to mitigate this effect. Among the three re
      references, REST is generally superior to AR for all factors compared, and LM
      performs worst. REST is insensitive to head model perturbation. AR is subject to
      electrodes coverage and dipole orientation but no close relation with channel
      number. SIGNIFICANCE: These results indicate that REST would be the first choice
      of re-reference and AR may be an alternative option for high level sensor noise
      case. Our findings may provide the helpful suggestions on how to obtain the EEG
      potentials as accurately as possible for cognitive neuroscientists and
      clinicians.

PMID- 29368699
TI  - Antiphospholipid syndrome.
AB  - This corrects the article DOI: 10.1038/nrdp.2017.103.

PMID- 29368698
TI  - Ingenol-3-Angelate Suppresses Growth of Melanoma Cells and Skin Tumor Development
      by Downregulation of NF-kappaB-Cox2 Signaling.
AB  - BACKGROUND A recent focus in skin cancer prevention intervenes though modulating
      molecular links between inflammation and cell growth signaling, such as NF
      kappaB. This study elucidates the effect of a non-tumor promoting phorbol ester,
      ingenol-3-angelate (I3A), on the growth of human melanoma cells and on the 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation and 7,12
      Dimethylbenz(a)anthracene (DMBA)-induced skin carcinoma in mice. MATERIAL AND
      METHODS Cell viability was assessed by MTT assay, cell proliferation by
      clonogenic assay, apoptosis and cell cycle arrest was analyzed by flow cytometry,
      protein expression was studied by IHC and Western blotting, and gene expression
      by qPCR. RESULTS I3A suppressed the survival and proliferation of human melanoma
      cells with estimated IC50 values around 38 and 46 MUM for A2058 and HT144 cell,
      respectively. I3A activated the protein levels of PKCdelta and PKCepsilon, which
      induced apoptosis by activating caspase-9 and caspace-3 followed by lowering of
      mitochondrial membrane potential and enhancing DNA fragmentation. I3A induced G1
      phase cell cycle arrest as well as G2/M phase arrest in both cell lines. I3A
      inhibited the levels of NFkappaB p65 protein as well as phosphorylation of p65
      and its nuclear translocation. I3A suppressed the gene expression of NF-kappaB,
      COX-2 and iNOS. I3A inhibited TPA-induced inflammation and epidermal hyperplasia
      in female ICR mice by downregulating NF-kappaB and iNOS. I3A suppressed the
      growth of skin tumor in DMBA-induced mice in dose-dependent manner. CONCLUSIONS
      The mechanism of I3A induces apoptosis in human melanoma cells and suppresses
      skin inflammation and carcinoma via downregulation of NF-kappaB-iNOS-COX-2
      signaling.

PMID- 29368700
TI  - Arrhythmias: Noninvasive radioablation for VT.

PMID- 29368702
TI  - Acute coronary syndromes: Silent myocardial infarction increases the risk of
      heart failure.

PMID- 29368701
TI  - Effect of glucose-lowering therapies on heart failure.
AB  - Heart failure is one of the most common comorbidities of diabetes mellitus.
      Glucose-lowering therapies that can prevent heart failure or improve outcomes in
      patients with established heart failure are of critical importance among those
      with type 2 diabetes. Several types of glucose-lowering drugs have been assessed
      in this setting. Metformin has been shown to modestly improve the outcomes of
      patients with heart failure, whereas the effect of insulin in those with
      established heart failure is less clear. The effect of sulfonylureas on improving
      heart failure is controversial; observational reports have suggested that they
      are harmful in these patients, but these data have not been confirmed in
      randomized, controlled trials. Thiazolidinediones are contraindicated in patients
      with established heart failure and have also been known to cause heart failure.
      Furthermore, certain dipeptidyl peptidase 4 inhibitors seem to increase heart
      failure hospitalization. The effects of glucagon-like peptide 1 receptor agonists
      might differ in patients with or without established heart failure, particularly
      those with decompensated heart failure with a reduced ejection fraction. However,
      perhaps the most important finding has been that sodium/glucose cotransporter 2
      (SGLT2; also known as SLC5A2) inhibitors reduce heart failure hospitalizations
      and, in the case of empagliflozin, markedly reduce the rate of cardiovascular
      death. Given the known neutral (or even harmful) effects of other glucose
      lowering drugs on heart failure outcomes, SGLT2 inhibitors might well be
      considered the drug class of choice in patients with diabetes and heart failure,
      or in those at high risk of developing heart failure.

PMID- 29368703
TI  - Enhancement and sign change of magnetic correlations in a driven quantum many
      body system.
AB  - Periodic driving can be used to control the properties of a many-body state
      coherently and to realize phases that are not accessible in static systems. For
      example, exposing materials to intense laser pulses makes it possible to induce
      metal-insulator transitions, to control magnetic order and to generate transient
      superconducting behaviour well above the static transition temperature. However,
      pinning down the mechanisms underlying these phenomena is often difficult because
      the response of a material to irradiation is governed by complex, many-body
      dynamics. For static systems, extensive calculations have been performed to
      explain phenomena such as high-temperature superconductivity. Theoretical
      analyses of driven many-body Hamiltonians are more challenging, but approaches
      have now been developed, motivated by recent observations. Here we report an
      experimental quantum simulation in a periodically modulated hexagonal lattice and
      show that antiferromagnetic correlations in a fermionic many-body system can be
      reduced, enhanced or even switched to ferromagnetic correlations (sign reversal).
      We demonstrate that the description of the many-body system using an effective
      Floquet-Hamiltonian with a renormalized tunnelling energy remains valid in the
      high-frequency regime by comparing the results to measurements in an equivalent
      static lattice. For near-resonant driving, the enhancement and sign reversal of
      correlations is explained by a microscopic model of the system in which the
      particle tunnelling and magnetic exchange energies can be controlled
      independently. In combination with the observed sufficiently long lifetimes of
      the correlations in this system, periodic driving thus provides an alternative
      way of investigating unconventional pairing in strongly correlated systems
      experimentally.

PMID- 29368704
TI  - A photophoretic-trap volumetric display.
AB  - Free-space volumetric displays, or displays that create luminous image points in
      space, are the technology that most closely resembles the three-dimensional
      displays of popular fiction. Such displays are capable of producing images in
      'thin air' that are visible from almost any direction and are not subject to
      clipping. Clipping restricts the utility of all three-dimensional displays that
      modulate light at a two-dimensional surface with an edge boundary; these include
      holographic displays, nanophotonic arrays, plasmonic displays, lenticular or
      lenslet displays and all technologies in which the light scattering surface and
      the image point are physically separate. Here we present a free-space volumetric
      display based on photophoretic optical trapping that produces full-colour
      graphics in free space with ten-micrometre image points using persistence of
      vision. This display works by first isolating a cellulose particle in a
      photophoretic trap created by spherical and astigmatic aberrations. The trap and
      particle are then scanned through a display volume while being illuminated with
      red, green and blue light. The result is a three-dimensional image in free space
      with a large colour gamut, fine detail and low apparent speckle. This platform,
      named the Optical Trap Display, is capable of producing image geometries that are
      currently unobtainable with holographic and light-field technologies, such as
      long-throw projections, tall sandtables and 'wrap-around' displays.

PMID- 29368706
TI  - Kiss-and-tell way to track cell contacts.

PMID- 29368705
TI  - Early episodes of high-pressure core formation preserved in plume mantle.
AB  - The decay of short-lived iodine (I) and plutonium (Pu) results in xenon (Xe)
      isotopic anomalies in the mantle that record Earth's earliest stages of
      formation. Xe isotopic anomalies have been linked to degassing during accretion,
      but degassing alone cannot account for the co-occurrence of Xe and tungsten (W)
      isotopic heterogeneity in plume-derived basalts and their long-term preservation
      in the mantle. Here we describe measurements of I partitioning between liquid Fe
      alloys and liquid silicates at high pressure and temperature and propose that Xe
      isotopic anomalies found in modern plume rocks (that is, rocks with elevated
      3He/4He ratios) result from I/Pu fractionations during early, high-pressure
      episodes of core formation. Our measurements demonstrate that I becomes
      progressively more siderophile as pressure increases, so that portions of mantle
      that experienced high-pressure core formation will have large I/Pu depletions not
      related to volatility. These portions of mantle could be the source of Xe and W
      anomalies observed in modern plume-derived basalts. Portions of mantle involved
      in early high-pressure core formation would also be rich in FeO, and hence denser
      than ambient mantle. This would aid the long-term preservation of these mantle
      portions, and potentially points to their modern manifestation within seismically
      slow, deep mantle reservoirs with high 3He/4He ratios.

PMID- 29368708
TI  - Bashing holes in the tale of Earth's troubled youth.

PMID- 29368710
TI  - Science after a year of President Trump.

PMID- 29368712
TI  - A beacon at the dawn of the Universe.

PMID- 29368711
TI  - Most popular public searches on gene names.

PMID- 29368714
TI  - Gene names can confound most-searched listings.

PMID- 29368713
TI  - Controversial femur could belong to ancient human relative.

PMID- 29368715
TI  - Frontiers in biology.

PMID- 29368716
TI  - Science must get ready for the next global flu crisis.

PMID- 29368717
TI  - Meet the street animals that stole scientists' hearts.

PMID- 29368718
TI  - Don't attack science agencies for political gain.

PMID- 29368719
TI  - Test proxy carbon prices as decision-making tools.

PMID- 29368720
TI  - First monkeys cloned with technique that made Dolly the sheep.

PMID- 29368721
TI  - Robust research needs many lines of evidence.

PMID- 29368722
TI  - Satellite images show China going green.

PMID- 29368723
TI  - Science has a gambling problem.

PMID- 29368724
TI  - China declared world's largest producer of scientific articles.

PMID- 29368727
TI  - Brief US shutdown, harassment data and electric fishing.

PMID- 29368725
TI  - Undergraduate physics labs don't improve US students' exam scores.

PMID- 29368728
TI  - Eighty years of superfluidity.

PMID- 29368729
TI  - US ecologists earn more in government than in academia.

PMID- 29368730
TI  - Regulate prescription of Chinese medicines.

PMID- 29368731
TI  - The lost art of looking at plants.

PMID- 29368733
TI  - US researchers relieved as government shutdown ends.

PMID- 29368732
TI  - Technology to watch in 2018.

PMID- 29368734
TI  - German scientists hope for windfall from incoming government.

PMID- 29368736
TI  - Vaccine boosters.

PMID- 29368737
TI  - China's ban on imported plastic waste could be a game changer.

PMID- 29368738
TI  - Ageing-related receptors resolved.

PMID- 29368740
TI  - Calestous Juma (1953-2017).

PMID- 29368739
TI  - Trapped particle makes 3D images.

PMID- 29368741
TI  - Tumour metabolism: The promoter becomes the suppressor.

PMID- 29368742
TI  - Oncogenes: Driving immune evasion.

PMID- 29368743
TI  - Gastric cancer: Risk analysis.

PMID- 29368744
TI  - Tumour microenvironment: Radical changes.

PMID- 29368745
TI  - Immunotherapy: Bad B cells.

PMID- 29368746
TI  - Corrigendum: Ribosome biogenesis in cancer: new players and therapeutic avenues.
AB  - This corrects the article DOI: 10.1038/nrc.2017.104.

PMID- 29368747
TI  - Metabolism: Fusion power.

PMID- 29368748
TI  - Streams as Entanglement of Nature and Culture: European Upper Paleolithic River
      Systems and Their Role as Features of Spatial Organization.
AB  - Large river valleys have long been seen as important factors to shape the
      mobility, communication, and exchange of Pleistocene hunter-gatherers. However,
      rivers have been debated as either natural entities people adapt and react to or
      as cultural and meaningful entities people experience and interpret in different
      ways. Here, we attempt to integrate both perspectives. Building on theoretical
      work from various disciplines, we discuss the relationship between biophysical
      river properties and sociocultural river semantics and suggest that understanding
      a river's persona is central to evaluating its role in spatial organization. By
      reviewing the literature and analyzing European Upper Paleolithic site
      distribution and raw material transfer patterns in relation to river catchments,
      we show that the role of prominent rivers varies considerably over time. Both
      ecological and cultural factors are crucial to explaining these patterns. Whereas
      the Earlier Upper Paleolithic record displays a general tendency toward
      conceiving rivers as mobility guidelines, the spatial consolidation process after
      the colonization of the European mainland is paralleled by a trend of
      conceptualizing river regimes as frontiers, separating archaeological entities,
      regional groups, or local networks. The Late Upper Paleolithic Magdalenian,
      however, is characterized again by a role of rivers as mobility and communication
      vectors. Tracing changing patterns in the role of certain river regimes through
      time thus contributes to our growing knowledge of human spatial behavior and
      helps to improve our understanding of dynamic and mutually informed human
      environment interactions in the Paleolithic.

PMID- 29368749
TI  - On Textual Analysis and Machine Learning for Cyberstalking Detection.
AB  - Cyber security has become a major concern for users and businesses alike.
      Cyberstalking and harassment have been identified as a growing anti-social
      problem. Besides detecting cyberstalking and harassment, there is the need to
      gather digital evidence, often by the victim. To this end, we provide an overview
      of and discuss relevant technological means, in particular coming from text
      analytics as well as machine learning, that are capable to address the above
      challenges. We present a framework for the detection of text-based cyberstalking
      and the role and challenges of some core techniques such as author
      identification, text classification and personalisation. We then discuss PAN, a
      network and evaluation initiative that focusses on digital text forensics, in
      particular author identification.

PMID- 29368750
TI  - From Environment to Landscape. Reconstructing Environment Perception Using
      Numerical Data.
AB  - The paper introduces a method that links environment to landscape. The
      environment-landscape divide appears because of epistemological differences:
      since studying the landscape involves describing the world as it was perceived by
      humans, it is difficult to access this dimension through the numerical data that
      we employ when studying the environment. We approach the issue of non
      correspondence between environment and landscape knowledge using fuzzy logic. The
      numerical data describing two geomorphometric parameters, slope and modified
      topographic index, are split each into three classes with overlapping borders.
      The classes are then fused into four qualitative categories: flat wet, steep dry,
      flat dry, and gradual moist. These four categories have direct correspondence in
      the real world and can be observed by people through simple perception. The
      correspondence of such categories to peoples' perception is checked against
      evidence of past human settlement in three areas coming from Turkey, Serbia, and
      Syria. The identified qualitative categories resemble the way people categorized
      their landscape in all but the second case study. Humans were able to perceive
      and choose areas which correspond to gradual moist in Turkey and broadly to flat
      wet in Syria. However, for the Serbian example, the results are inconclusive.

PMID- 29368751
TI  - The Contextual Cat: Human-Animal Relations and Social Meaning in Anglo-Saxon
      England.
AB  - The growing popularity of relational approaches to agency amongst archaeologists
      has led to increased attention on the specific contexts of interaction between
      humans and their material worlds. Within such viewpoints, non-humans are
      perceived as agents in their own right and placed on an equal footing with
      humans, with both acting to generate social categories in past cultures. However,
      to date, the focus of these interpretative models has been overwhelmingly
      directed towards inanimate objects. Animals are generally absent from these
      discussions, despite their ubiquity in past societies and the frequently central
      roles they held within daily lives and social relations. Moreover, living animals
      are set apart from material culture because, like humans, they are usually aware
      of their environs and are capable of physically responding to them. This ability
      to 'act back' would have made human-animal interactions extremely dynamic and
      thus offers different conceptual challenges to archaeologists than when faced
      with objects. This paper demonstrates that the notion of performativity, combined
      with understanding of animals themselves, can help to comprehend these relations.
      It does so by focusing on one particular species, the domestic cat, in relation
      to Anglo-Saxon England. The characteristics and behaviour of these animals
      affected the ways in which humans perceived and interacted with them, so that
      just one individual cat could be categorised in a range of different ways. The
      classification of animals was thus just as fluid, if not more so, as that of
      objects and highlights the need to incorporate the former into reconstructions of
      the social in archaeological research.

PMID- 29368753
TI  - The difference between LSMC and replicating portfolio in insurance liability
      modeling.
AB  - Solvency II requires insurers to calculate the 1-year value at risk of their
      balance sheet. This involves the valuation of the balance sheet in 1 year's time.
      As for insurance liabilities, closed-form solutions to their value are generally
      not available, insurers turn to estimation procedures. While pure Monte Carlo
      simulation set-ups are theoretically sound, they are often infeasible in
      practice. Therefore, approximation methods are exploited. Among these, least
      squares Monte Carlo (LSMC) and portfolio replication are prominent and widely
      applied in practice. In this paper, we show that, while both are variants of
      regression-based Monte Carlo methods, they differ in one significant aspect.
      While the replicating portfolio approach only contains an approximation error,
      which converges to zero in the limit, in LSMC a projection error is additionally
      present, which cannot be eliminated. It is revealed that the replicating
      portfolio technique enjoys numerous advantages and is therefore an attractive
      model choice.

PMID- 29368752
TI  - Predictors and short-term outcomes of recurrent pulmonary tuberculosis, Uganda: a
      cohort study.
AB  - Introduction: Recurrent tuberculosis (TB) occurring >2 years after completing
      treatment for a prior TB episode is most often due to reinfection with a new
      strain of M. tuberculosis. Objectives: We determined the prevalence and outcome
      of late recurrent TB among hospitalized patients in Kampala, Uganda. Methods: We
      conducted a retrospective analysis of patients admitted to Mulago Hospital who
      had cough of >2 weeks' duration and completed TB treatment >2 years prior to
      admission. All patients had mycobacterial culture performed on two sputum
      specimens and vital status ascertained 2-months post-enrollment. We performed
      modeling to identify predictors of recurrent TB and of survival. Results: Among
      234 patients, 84 (36%) had recurrent TB. Independent predictors included younger
      age (aOR=0.64, 95% CI=0.42-0.97, p=0.04), chest pain >2 weeks (aOR=3.32, 95%
      CI=1.38-8.02, p=0.007), severe weight loss >=5 kilograms (aOR=4.88, 95% CI=1.66
      14.29, p=0.004) and presence of >=1 WHO danger sign of severe illness (aOR=3.55,
      95% CI=1.36-9.29, p=0.01). Two-month mortality was 17.8% (95% CI=10.5-29.2%), and
      was higher among patients not initiated on TB treatment (aHR=16.67, 95% CI=1.18
      200, p=0.04), not on ART if HIV-positive (aHR=16.99, 95% CI=1.17-246.47, p=0.04)
      and with a history of smoking (aHR=1.20, 95% CI=1.03-1.40, p=0.02). Conclusion:
      The high prevalence of late recurrent TB likely reflects high levels of TB
      transmission in Kampala. Increased use of empiric TB treatment and early ART
      treatment initiation if HIV-positive should be considered in patients with a
      prior history of TB, particularly if young, with weight loss >=5kgs, chest pain
      >2 weeks or >=1 WHO danger sign of severe illness.

PMID- 29368754
TI  - Settlement Dynamics and Hierarchy from Agent Decision-Making: a Method Derived
      from Entropy Maximization.
AB  - This paper presents an agent-based complex system simulation of settlement
      structure change using methods derived from entropy maximization modeling. The
      approach is applied to model the movement of people and goods in urban settings
      to study how settlement size hierarchy develops. While entropy maximization is
      well known for assessing settlement structure change over different
      spatiotemporal settings, approaches have rarely attempted to develop and apply
      this methodology to understand how individual and household decisions may affect
      settlement size distributions. A new method developed in this paper allows
      individual decision-makers to chose where to settle based on social-environmental
      factors, evaluate settlements based on geography and relative benefits, while
      retaining concepts derived from entropy maximization with settlement size
      affected by movement ability and site attractiveness feedbacks. To demonstrate
      the applicability of the theoretical and methodological approach, case study
      settlement patterns from the Middle Bronze (MBA) and Iron Ages (IA) in the Iraqi
      North Jazirah Survey (NJS) are used. Results indicate clear differences in
      settlement factors and household choices in simulations that lead to settlement
      size hierarchies comparable to the two evaluated periods. Conflict and socio
      political cohesion, both their presence and absence, are suggested to have major
      roles in affecting the observed settlement hierarchy. More broadly, the model is
      made applicable for different empirically based settings, while being generalized
      to incorporate data uncertainty, making the model useful for understanding
      urbanism from top-down and bottom-up perspectives.

PMID- 29368755
TI  - LIVIVO - the Vertical Search Engine for Life Sciences.
AB  - The explosive growth of literature and data in the life sciences challenges
      researchers to keep track of current advancements in their disciplines. Novel
      approaches in the life science like the One Health paradigm require integrated
      methodologies in order to link and connect heterogeneous information from
      databases and literature resources. Current publications in the life sciences are
      increasingly characterized by the employment of trans-disciplinary methodologies
      comprising molecular and cell biology, genetics, genomic, epigenomic,
      transcriptional and proteomic high throughput technologies with data from humans,
      plants, and animals. The literature search engine LIVIVO empowers retrieval
      functionality by incorporating various literature resources from medicine,
      health, environment, agriculture and nutrition. LIVIVO is developed in-house by
      ZB MED - Information Centre for Life Sciences. It provides a user-friendly and
      usability-tested search interface with a corpus of 55 Million citations derived
      from 50 databases. Standardized application programming interfaces are available
      for data export and high throughput retrieval. The search functions allow for
      semantic retrieval with filtering options based on life science entities. The
      service oriented architecture of LIVIVO uses four different implementation layers
      to deliver search services. A Knowledge Environment is developed by ZB MED to
      deal with the heterogeneity of data as an integrative approach to model, store,
      and link semantic concepts within literature resources and databases. Future work
      will focus on the exploitation of life science ontologies and on the employment
      of NLP technologies in order to improve query expansion, filters in faceted
      search, and concept based relevancy rankings in LIVIVO.

PMID- 29368756
TI  - Rank-based methods for modeling dependence between loss triangles.
AB  - In order to determine the risk capital for their aggregate portfolio, property
      and casualty insurance companies must fit a multivariate model to the loss
      triangle data relating to each of their lines of business. As an inadequate
      choice of dependence structure may have an undesirable effect on reserve
      estimation, a two-stage inference strategy is proposed in this paper to assist
      with model selection and validation. Generalized linear models are first fitted
      to the margins. Standardized residuals from these models are then linked through
      a copula selected and validated using rank-based methods. The approach is
      illustrated with data from six lines of business of a large Canadian insurance
      company for which two hierarchical dependence models are considered, i.e., a
      fully nested Archimedean copula structure and a copula-based risk aggregation
      model.

PMID- 29368757
TI  - Personal, Political, Pedagogic: Challenging the Binary Bind in Archaeological
      Teaching, Learning and Fieldwork.
AB  - In this paper, we consider how we can undercut the various binaries of gender and
      sexuality in archaeological practice and particularly in our teaching. We argue
      that taking an assemblage theory approach enables us to look at the multiplicity
      of identities of those practicing archaeology as different and intersecting
      assemblages that bring one another into being through their connections at
      different scales. In particular, we examine how this approach can be applied to
      archaeological pedagogy and how this in turn enables us to move away from modern
      binary distinctions about sex and gender identities from the 'bottom up',
      fostering an approach in our students that will then go on to be developed in
      professional practice.

PMID- 29368758
TI  - Modelling the effect of religion on human empathy based on an adaptive temporal
      causal network model.
AB  - Background: Religion is a central aspect of many individuals' lives around the
      world, and its influence on human behaviour has been extensively studied from
      many different perspectives. Methods: The current study integrates a number of
      these perspectives into one adaptive temporal-causal network model describing the
      mental states involved, their mutual relations, and the adaptation of some of
      these relations over time due to learning. Results: By first developing a
      conceptual representation of a network model based on the literature, and then
      formalizing this model into a numerical representation, simulations can be done
      for almost any kind of religion and person, showing different behaviours for
      persons with different religious backgrounds and characters. The focus was mainly
      on the influence of religion on human empathy and dis-empathy, a topic very
      relevant today. Conclusions: The developed model could be valuable for many uses,
      involving support for a better understanding, and even prediction, of the
      behaviour of religious individuals. It is illustrated for a number of different
      scenarios based on different characteristics of the persons and of the religion.

PMID- 29368759
TI  - Ischemic preconditioning treatment of astrocytes transfers ischemic tolerance to
      neurons.
AB  - Ischemic preconditioning (IPC) represents a potential therapy against cerebral
      ischemia. While our group has previously shown IPC to induce neuroprotection
      through various pathways, the role of astrocytes in supporting IPC-induced
      neuroprotection has not been extensively studied. Astrocyte-derived lactate has
      gained attention as a potential soluble mediator through which astrocytes could
      impart ischemic tolerance to neurons. Therefore, the goal of this study was to
      determine if i) IPC-treatment of astrocytes alone could transfer ischemic
      tolerance to neurons; ii) if IPC-treatment of astrocytes increases lactate
      production; and if iii) exogenous lactate administration to neurons could induce
      neuroprotection against lethal ischemia in vitro. For this purpose, a co-culture
      system was used and modified from a previous method. This system allows
      astrocytes and neurons to be separated by a physical barrier, while allowing
      secreted substances from either cell type to interact with each other. Oxygen
      glucose deprivation was used as a model of cerebral ischemia and IPC in cultured
      rodent astrocytes and neurons. Neurons incubated with IPC-treated astrocytes were
      significantly protected against lethal ischemic injury compared to neurons
      incubated with sham-treated astrocytes. In addition, IPC-treatment of astrocytes
      significantly increased lactate secretion into the extracellular media. Finally,
      exogenous lactate administration can significantly attenuate cell death in
      neuronal cultures following exposure to lethal OGD. Our results suggest that IPC
      treatment of astrocytes alone can transfer ischemic tolerance to neurons. In
      addition, the ability of IPC to increase lactate production in astrocytes suggest
      that lactate could represent a neuroprotective agent to protect neurons against
      lethal ischemic injury.

PMID- 29368760
TI  - Scalable DB+IR Technology: Processing Probabilistic Datalog with HySpirit.
AB  - Probabilistic Datalog (PDatalog, proposed in 1995) is a probabilistic variant of
      Datalog and a nice conceptual idea to model Information Retrieval in a logical,
      rule-based programming paradigm. Making PDatalog work in real-world applications
      requires more than probabilistic facts and rules, and the semantics associated
      with the evaluation of the programs. We report in this paper some of the key
      features of the HySpirit system required to scale the execution of PDatalog
      programs. Firstly, there is the requirement to express probability estimation in
      PDatalog. Secondly, fuzzy-like predicates are required to model vague predicates
      (e.g. vague match of attributes such as age or price). Thirdly, to handle large
      data sets there are scalability issues to be addressed, and therefore, HySpirit
      provides probabilistic relational indexes and parallel and distributed
      processing. The main contribution of this paper is a consolidated view on the
      methods of the HySpirit system to make PDatalog applicable in real-scale
      applications that involve a wide range of requirements typical for data
      (information) management and analysis.

PMID- 29368761
TI  - Chiral effects on the final step of an octahedron-shaped coordination capsule
      self-assembly.
AB  - The final step of the self-assembly of an octahedron-shaped coordination capsule
      was investigated by a novel theoretical method. Two different reaction pathways
      were detected and classified by the chiral types of constituents, which addressed
      the possibility of chiral effects on the self-assembly process.

PMID- 29368762
TI  - Effects of structures of bidentate Schiff base type bonded-ligands derived from
      benzaldehyde on the photoluminescence performance of polymer-rare earth
      complexes.
AB  - Two kinds of bidentate Schiff base ligands derived from benzaldehyde,
      benzaldehyde/m-aminophenol (BAMA) type and benzaldehyde/glutamic acid (BAGL) type
      ligands, were synchronously synthesized and bonded on the backbone of polysulfone
      (PSF) through molecular design and by polymer reactions, and two functional
      polymers, PSF-BAMA and PSF-BAGL, were obtained. Then two series of novel
      luminescent Schiff base-type polymer-rare earth complexes were prepared via
      coordination reactions. In this work, the effects of the structures of the bonded
      ligands on the photoluminescence performance of the complexes were investigated
      in detail, and for the different photophysical properties of the prepared
      complexes, relevant theoretical explanations were given. The experimental results
      show that the bonded ligand BAMA can strongly sensitize the fluorescence emission
      of Eu(iii) ions, and the binary complex PSF-(BAMA)3-Eu(iii) emits strong red
      fluorescence under UV light. The reason for this lies in the fact that a larger
      conjugate pi-bond system is contained in the structure of BAMA, and so the
      triplet state of BAMA can be matched with the resonant energy level of the
      Eu(iii) ion. While the bonded ligand BAGL can effectively sensitize the
      fluorescence emission of Tb(iii) ions, the binary complex PSF-(BAGL)3-Tb(iii)
      exhibits very strong green fluorescence under UV light. The reason is that a
      smaller conjugate pi-bond system is contained in the structure of BAGL and there
      is a good energy level matching between the triplet state of BAGL and the
      resonant energy level of the Tb(iii) ion. The fluorescence intensities of the two
      ternary complexes, PSF-(BAMA)3-Eu(iii)-(Phen)1 (phenanthroline, Phen) and PSF
      (BAGL)3-Tb(iii)-(Phen)1, are much stronger than that of the corresponding binary
      complex because Phen as the second ligand has two effects, the effect of
      synergistic coordination with the first ligand and the effect of replacing the
      coordinated water around the central ion, and it has been confirmed by
      fluorescence spectroscopy and thermogravimetric analysis.

PMID- 29368763
TI  - Physical and compositional analysis of differently cultured 3D human skin
      equivalents by confocal Raman spectroscopy.
AB  - Three-dimensional skin equivalents are increasingly gaining acceptance as non
      animal based experimental models of human skin. They are particularly suited to
      studying differences in physical and compositional properties of normal and
      diseased skin and their impact on the skin's barrier function. Typically, a
      culture protocol yielding a model of normal skin is modified to create a model
      simulating a pathology. Skin layer thicknesses and lipid/protein contents are
      compared using methods that are invasive, precluding further experiments on the
      same replicates, and which may be prone to artefacts. We show here that confocal
      Raman spectroscopy (CRS) is a valuable method for non-invasive discrimination of
      skin equivalents grown under different culture conditions. Using 3D full
      thickness skin equivalents developed in-house, we measure significant differences
      in stratum corneum and viable epidermis apparent thicknesses resulting from a 7
      day difference in the cultures' air-lift phase and from supplementation of the
      culture medium with interleukin 4. Furthermore, stratum corneum thicknesses
      obtained by CRS are up to 2.6-fold higher than values measured from histological
      photomicrographs. Regarding composition, CRS reveals the differential effects of
      the culture protocol modifications on ceramide, cholesterol and protein
      composition as a function of depth in the stratum corneum.

PMID- 29368764
TI  - Raman spectroscopy of graphene-based materials and its applications in related
      devices.
AB  - Graphene-based materials exhibit remarkable electronic, optical, and mechanical
      properties, which has resulted in both high scientific interest and huge
      potential for a variety of applications. Furthermore, the family of graphene
      based materials is growing because of developments in preparation methods. Raman
      spectroscopy is a versatile tool to identify and characterize the chemical and
      physical properties of these materials, both at the laboratory and mass
      production scale. This technique is so important that most of the papers
      published concerning these materials contain at least one Raman spectrum. Thus,
      here, we systematically review the developments in Raman spectroscopy of graphene
      based materials from both fundamental research and practical (i.e., device
      applications) perspectives. We describe the essential Raman scattering processes
      of the entire first- and second-order modes in intrinsic graphene. Furthermore,
      the shear, layer-breathing, G and 2D modes of multilayer graphene with different
      stacking orders are discussed. Techniques to determine the number of graphene
      layers, to probe resonance Raman spectra of monolayer and multilayer graphenes
      and to obtain Raman images of graphene-based materials are also presented. The
      extensive capabilities of Raman spectroscopy for the investigation of the
      fundamental properties of graphene under external perturbations are described,
      which have also been extended to other graphene-based materials, such as graphene
      quantum dots, carbon dots, graphene oxide, nanoribbons, chemical vapor deposition
      grown and SiC epitaxially grown graphene flakes, composites, and graphene-based
      van der Waals heterostructures. These fundamental properties have been used to
      probe the states, effects, and mechanisms of graphene materials present in the
      related heterostructures and devices. We hope that this review will be beneficial
      in all the aspects of graphene investigations, from basic research to material
      synthesis and device applications.

PMID- 29368765
TI  - A self-assembled peroxidase from 5'-GMP and heme.
AB  - Guanosine 5'-monophosphate (5'-GMP) and Fe(iii)-heme form a supramolecular
      catalyst with peroxidase activity. Catalysis, which depends on self-assembly of
      5'-GMP into a G-quadruplex that binds hemin, can be modulated by nucleotide
      concentration, temperature and the identity of the nucleotide's sugar.

PMID- 29368766
TI  - Facile synthesis of pyrroloindoles via a rhodium(ii)-catalyzed annulation of 3
      benzylidene-indolin-2-ones and alpha-imino carbenes.
AB  - The annulation of 3-benzylidene-indolin-2-ones with alpha-imino rhodium carbenes
      generated in situ from N-sulfonyl-1,2,3-triazoles is presented. Through the
      appropriate choice of catalyst, the reactions can be reasonably modulated, and
      consequently, a number of pyrroloindole derivatives were constructed in moderate
      to excellent yields.

PMID- 29368767
TI  - Task-specific design of a hierarchical porous aromatic framework as an
      ultrastable platform for large-sized catalytic active site binding.
AB  - An amine-tagged hierarchical porous aromatic framework PAF70-NH2 with ultra
      stability and narrowly distributed mesopores was synthesized. PAF70-NH2 has high
      potential for covalently immobilizing a relatively large-sized catalyst inside
      its pores. This work gave a perfect example of using PAF70-NH2 as a platform for
      completely recyclable heterogeneous organocatalysis.

PMID- 29368768
TI  - Designing anisotropic cyanometallate coordination polymers with unidirectional
      thermal expansion (TE): 2D zero and 1D colossal positive TE.
AB  - Oxidative addition of halogens to tetracyanoplatinate results in the formation of
      a Pt(iv)-building block that, combined with Cu(ii), forms coordination polymers
      Cu(H2O)2[PtX2(CN)4] (X = Br, Cl). These materials exhibit directional anisotropic
      thermal expansion: nearly zero expansion within the cyanometallate sheets and
      positive thermal expansion in the third dimension.

PMID- 29368770
TI  - Co2P quantum dot embedded N, P dual-doped carbon self-supported electrodes with
      flexible and binder-free properties for efficient hydrogen evolution reactions.
AB  - Transition metal phosphides (TMPs) are considered to be superb catalysts for
      water splitting. In this work, we introduce an efficient strategy to fabricate
      dicobalt phosphide (Co2P) quantum dots embedded in N, P dual-doped carbon
      (Co2P@NPC) on carbon cloth (Co2P@NPC/CC) by in situ carbonization of cobalt ion
      induced phytic acid (PA) and polyaniline (PANI) macromolecule precursors. As a
      highly efficient self-supported electrode, it has a low onset overpotential (74
      mV at 1 mA cm-2) approaching that of the commercial Pt/C catalyst for the
      hydrogen evolution reaction (HER) in acidic media. Meanwhile, it also shows very
      low overpotentials of only 116 and 129 mV at 10 mA cm-2 with robust stability in
      acidic and alkaline media, respectively.

PMID- 29368769
TI  - Robust light harvesting by a noisy antenna.
AB  - Photosynthetic light harvesting can be very efficient in solar energy conversion
      while taking place in a highly disordered and noisy physiological environment.
      This efficiency is achieved by the ultrafast speed of the primary photosynthetic
      processes, which is enabled by a delicate interplay of quantum effects,
      thermodynamics and environmental noise. The primary processes take place in light
      harvesting antennas built from pigments bound to a fluctuating protein scaffold.
      Here, we employ ultrafast single-molecule spectroscopy to follow fluctuations of
      the femtosecond energy transfer times in individual LH2 antenna complexes of
      purple bacteria. By combining single molecule results with ensemble spectroscopy
      through a unified theoretical description of both, we show how the protein
      fluctuations alter the excitation energy transfer dynamics. We find that from the
      thirteen orders of magnitude of possible timescales from picoseconds to minutes,
      the relevant fluctuations occur predominantly on a biological timescale of
      seconds, i.e. in the domain of slow protein motion. The measured spectra and
      dynamics can be explained by the protein modulating pigment excitation energies
      only. Moreover, we find that the small spread of pigment mean energies allows for
      excitation delocalization between the coupled pigments to survive. These unique
      features provide fast energy transport even in the presence of disorder. We
      conclude that this is the mechanism that enables LH2 to operate as a robust light
      harvester, in spite of its intrinsically noisy biological environment.

PMID- 29368771
TI  - Label-free and ultrasensitive detection of polynucleotide kinase activity at the
      single-cell level.
AB  - We develop a simple and label-free fluorescence method for the polynucleotide
      kinase (PNK) assay based on phosphorylation-triggered isothermal exponential
      amplification. This method exhibits ultrahigh sensitivity superior to most
      existing PNK assays. Importantly, this method enables sensitive detection of
      endogenous PNK activity at the single-cell level, holding great potential in
      clinical diagnosis and biomedical research.

PMID- 29368772
TI  - Transformative piezoelectric enhancement of P(VDF-TrFE) synergistically driven by
      nanoscale dimensional reduction and thermal treatment.
AB  - Despite the significant potential of organic piezoelectric materials in the
      electro-mechanical or mechano-electrical applications that require light and
      flexible material properties, the intrinsically low piezoelectric performance as
      compared to traditional inorganic materials has limited their full utilization.
      In this study, we demonstrate that dimensional reduction of poly(vinylidene
      fluoride trifluoroethylene) (P(VDF-TrFE)) at the nanoscale by electrospinning,
      combined with an appropriate thermal treatment, induces a transformative
      enhancement in piezoelectric performance. Specifically, the piezoelectric
      coefficient (d33) reached up to -108 pm V-1, approaching that of inorganic
      counterparts. Electrospun mats composed of thermo-treated 30 nm nanofibers with a
      thickness of 15 MUm produced a consistent peak-to-peak voltage of 38.5 V and a
      power output of 74.1 MUW at a strain of 0.26% while sustaining energy production
      over 10k repeated actuations. The exceptional piezoelectric performance was
      realized by the enhancement of piezoelectric dipole alignment and the
      materialization of flexoelectricity, both from the synergistic effects of
      dimensional reduction and thermal treatment. Our findings suggest that
      dimensionally controlled and thermally treated electrospun P(VDF-TrFE) nanofibers
      provide an opportunity to exploit their flexibility and durability for
      mechanically challenging applications while matching the piezoelectric
      performance of brittle, inorganic piezoelectric materials.

PMID- 29368773
TI  - Vacancy engineering of Cu2-xSe nanoparticles with tunable LSPR and magnetism for
      dual-modal imaging guided photothermal therapy of cancer.
AB  - The vacancies in the semiconductor nanocrystals not only induce unique
      properties, but also provide spaces for engineering them with multifunctions by
      the introduction of other elements. Herein, the vacancy of Cu2-xSe nanoparticles
      was tuned by doping with magnetic ferric ions (Fe3+) at room temperature, and the
      position and intensity of the near-infrared localized surface plasmon resonance
      (LSPR) in the resultant nanostructure can be finely controlled by altering the
      feeding amount of Fe3+ ions. The results of the density-functional theory (DFT)
      calculations show that both doping and replacement reactions are favourable.
      Owing to its tunable near-infrared absorption and magnetic property, the obtained
      hybrid nanostructure was demonstrated to be a novel nanotheranostic agent for
      effective deep-tissue photoacoustic imaging, magnetic resonance imaging, and
      photothermal therapy of cancer.

PMID- 29368774
TI  - Modular design of optically controlled protein affinity reagents.
AB  - Photopharmaceuticals can, in principle, be created by linking photoswitchable
      moieties to bioactive molecules. However, a general strategy for converting a
      therapeutic agent into its photoswitchable version is not currently available.
      Herein we propose a generalizable, modular approach for obtaining light
      controllable bioactive agents by modifying the scaffold of a protein affinity
      reagent using an azobenzene photoswitch.

PMID- 29368775
TI  - Evaluation of RGD functionalization in hybrid hydrogels as 3D neural stem cell
      culture systems.
AB  - The use of neural stem cells (NSCs) in cell therapy has become a powerful tool
      used for the treatment of central nervous system diseases, including traumatic
      brain and spinal cord injuries. However, a significant drawback is related to the
      limited viability after transplantation in situ. The design of three-dimensional
      (3D) scaffolds that are capable of resembling the architecture and physico
      chemical features of an extracellular environment could be a suitable approach to
      improve cell survival and preserve their cellular active phase over time. In this
      study, we investigated NSC adhesion and proliferation in hydrogel systems. In
      particular, we evaluated the effect of RGD binding domains on cell fate within
      the polymeric scaffold. The introduction of a tripeptide via hydrogel chemical
      functionalization improved the percentage of proliferating cells until 8 days
      after seeding when compared to the unmodified scaffold. The beneficial effects of
      this 3D culture system was further evident when compared to a NSC monolayer (2D)
      culture, resulting in an approximately 40% increase in cells in the active phases
      at 4 and 8 days, and maintained a difference of 25% until 21 days after seeding.

PMID- 29368776
TI  - Thermodynamic evidence of flexibility in H2O and CO2 absorption of transition
      metal ion exchanged zeolite LTA.
AB  - Gas absorption calorimetry has been employed to probe the intercation of water
      and carbon dioxide with transition metal ion (TM = Mn2+, Fe2+, Co2+, Cu2+, and
      Zn2+) exchanged zeolite A samples. There appears to be a two-phase region,
      indicative of a guest-induced flexibility transition, separating hydrated zeolite
      A and its dehydrated form, both of which have variable water content in the
      single phase region. The differential enthalpy of absorption as a function of
      water loading directly identifies different strengths of multiple interactions
      along with possible binding mechanisms of Zn-A and Mn-A exhibiting the highest
      water absorption with most exothermic initial enthalpies of -125.28 +/- 4.82 and 
      115.30 +/- 2.56 kJ mol-1. Zn-A and Mn-A also show moderately good capture ability
      for CO2 with zero-coverage negative enthalpies of -55.59 +/- 2.48 and -44.07 +/-
      1.53 kJ mol-1. The thermodynamic information derived from differential enthalpy,
      chemical potential and differential entropy elucidated the multistage interactive
      behavior of small guest molecules (H2O/CO2) and ion-exchanged frameworks.

PMID- 29368782
TI  - Dynamics of a colloidal particle near a thermoosmotic wall under illumination.
AB  - The effects of light on colloidal particles in solution are multiple, including
      transfer of photonic linear/angular momentum and heating of the particles or
      their surroundings. The temperature increase around colloidal particles due to
      light heating can drive a thermoosmotic flow along a nearby boundary wall, which
      significantly influences the motion of the particles. Here we perform mesoscopic
      dynamics simulations to study two typical scenarios, where thermoosmosis is
      critical. In the first scenario, we consider a light-absorbing colloidal particle
      heated by uniform illumination. Depending on the fluid-wall interactions, the
      thermoosmotic flow generated by the wall can exert a long-ranged hydrodynamic
      attraction or repulsion on the "hot" Brownian particle, which leads to a strong
      accumulation/depletion of the particle to/from the boundary. In the second
      scenario, we investigate the motion of a colloidal particle confined by an
      optical tweezer in a light-absorbing solution. In this case, thermoosmosis can
      induce a unidirectional rotation of the trapped particle, whose direction is
      determined by thermoosmotic properties of the wall. We show that colloidal
      particles near a thermoosmotic wall exhibit rich dynamics. Our results can be
      applied for the manipulation of colloidal particles in microfluidics.

PMID- 29368784
TI  - Oxygen vacancy regulation on tungsten oxides with specific exposed facets for
      enhanced visible-light-driven photocatalytic oxidation.
AB  - Introduced oxygen vacancy on WO3 with specific exposed facets was prepared
      through facile solvothermal treatment and different cooling methods. We
      demonstrated that the density of oxygen defects could be regulated by different
      cooling methods and speculated that oxygen vacancy with appropriate concentration
      range could promote photocatalytic activity through suppressing the recombination
      of photo-induced carriers. The specific exposed facets with higher oxidation
      efficiency were prepared by solvothermal reaction. WO3-A treated by air cooling
      exhibits the best photocatalytic oxygen evolution rate at 500 MUmol g-1 h-1 using
      AgNO3 as sacrifice agent under visible light (lambda > 400 nm) without any co
      catalysts, which is about 2 times higher than WO3-N without oxygen defects. This
      strategy, using different cooling methods to regulate oxygen vacancy
      concentration on tungsten oxides, could contribute to the design of other high
      efficiency photocatalysts.

PMID- 29368785
TI  - Electrophilic fluorination of stereodefined disubstituted silyl ketene
      hemiaminals en route to tertiary alpha-fluorinated carbonyl derivatives.
AB  - A highly diastereoselective synthesis of tertiary alpha-fluoro carbonyl compounds
      is reported in only two chemical steps from a simple alkyne through the reaction
      of stereodefined fully substituted silyl ketene hemiaminal derivatives with
      Selectfluor.

PMID- 29368787
TI  - Correction: Geometric frustration and compatibility conditions for two
      dimensional director fields.
AB  - Correction for 'Geometric frustration and compatibility conditions for two
      dimensional director fields' by Idan Niv et al., Soft Matter, 2018, DOI: .

PMID- 29368788
TI  - New insights into the nature of semi-soft elasticity and "mechanical-Freedericksz
      transitions" in liquid crystal elastomers.
AB  - The mechanical properties of an all-acrylate liquid crystal elastomer (LCE) with
      a glass transition of 14 +/- 1  degrees C are reported. The highly nonlinear load
      curve has a characteristic shape associated with semi-soft elasticity (SSE).
      Conversely, measurements of the director orientation throughout tensile loading
      instead indicate a "mechanical-Freedericksz" transition (MFT). Values of the step
      length anisotropy, r, are independently calculated from the theories of SSE (r =
      3.2 +/- 0.4), MFT (9.3 < r < 30.0) and thermally-induced length change (r = 3.8
      +/- 0.5). From simultaneously recorded polarising microscopy textures, the
      consequences of the above discrepancies are considered. Further, a mechanically
      induced negative order parameter is observed. Results show the tensile load curve
      shape cannot solely be used to determine the underlying physics. Consequently,
      the LCE properties cannot be fully described by theories of SSE or MFTs alone.
      This suggests that the theory of LCEs is not yet complete. The conclusions
      suggest that both the LC order parameter and r must be functions of the
      mechanical deformation.

PMID- 29368789
TI  - Techniques for Repair of Obstetric Anal Sphincter Injuries.
AB  - Importance: Obstetric anal sphincter injuries (OASISs) complicate up to 11% of
      vaginal deliveries; obstetricians must be able to recognize and manage these
      technically challenging injuries. Objective: The aim of this study was to share
      our approach for management of these challenging complications of childbirth
      based on a multidisciplinary collaboration between general obstetrician
      gynecologists, maternal fetal medicine specialists, and female pelvic medicine
      and reconstructive surgeons established at our institution. Evidence Acquisition:
      A systematic literature search was performed in 3 search engines: PubMed 1946-,
      EMBASE 1947-, and the Cochrane Database of Systematic Reviews using keywords
      obstetric anal sphincter injuries and episiotomy repair. Results: Identification
      should begin with an assessment of risk factors, notably nulliparity and
      operative vaginal delivery, consistently associated with the highest risk of
      OASISs, and proceed with a thorough examination to grade the degree of
      laceration. Repair should be performed or supervised by an experienced clinician
      in an operating room with either regional or general anesthesia. The external
      anal sphincter may be repaired using either an overlapping or end-to-end
      anastomosis. Providers should be comfortable with both approaches as the degree
      of laceration may necessitate one approach over the other. We advocate for use of
      monofilament suture on all layers to decrease risk of bacterial seeding, as well
      as preoperative antibiotics and postoperative bowel regimen, which are associated
      with improved outcomes. Conclusions and Relevance: Long-term sequelae, including
      pain, dyspareunia, and fecal incontinence, significantly impact quality of life
      for many patients who suffer OASISs and may be avoided if evidence-based
      guidelines for recognition and repair are utilized.

PMID- 29368790
TI  - Pravastatin for Preventing and Treating Preeclampsia: A Systematic Review.
AB  - Importance: We have performed a systematic search to summarize the role of
      statins for preventing and treating severe preeclampsia. Objective: The aim of
      this study was to examine whether pravastatin is a useful and safe alternative
      for treating preeclampsia during pregnancy. Evidence Acquisition: A systematic
      MEDLINE (PubMed) search was performed (1979 to June 2017), which was restricted
      to articles published in English, using the relevant key words of "statins,"
      "pregnancy," "preeclampsia," "obstetrical antiphospholipid syndrome," and
      "teratogenicity." Results: The initial search provided 296 articles. Finally, 146
      articles were related to the use of statins during pregnancy, regarding their
      effect on the fetus and the treatment of preeclampsia. Ten studies were related
      to in vitro studies, 25 in animals, and 24 in humans (13 case report series and
      11 cohort studies). We found 84 studies on reviews of such guidelines on
      cardiovascular disease (35 studies), use of statins in the antiphospholipid
      syndrome (25 studies), statin's specific use during pregnancy (13 studies), or
      preeclampsia treatment (11 studies). Conclusions: Although the studies are of
      poor quality, the rate of major congenital abnormalities in the newborn exposed
      to statins during pregnancy is no higher than the expected when compared with
      overall risk population. The review shows a potential beneficial role of statins
      in preventing and treating severe preeclampsia that needs to be evaluated through
      well-designed clinical trials. Relevance: This update could influence positively
      the clinical practice, giving an alternative therapy for clinicians who treat
      preeclampsia, particularly in severe cases.

PMID- 29368791
TI  - Contraceptive Care of Obese Women.
AB  - Importance: In the United States, 27% of reproductive-aged women are overweight,
      and 35% are obese. Until recently, contraceptive research excluded women greater
      than 130% of their ideal body weight. Gaps in data limit evidence-based decision
      making for effective contraceptive counseling and management in this rapidly
      growing population. Objectives: The aims of this summary are to review the
      benefits, adverse effects, and risk factors associated with contraceptive methods
      in obese women, with special attention to effectiveness, and provide
      contraceptive management and counseling recommendations for best clinical
      practice. Evidence Acquisition: We performed a thorough search of PubMed for
      current literature, including original research articles, review articles, and
      guidelines on contraceptive counseling and management in obese women in the
      United States. We reviewed the body of evidence with special attention to studies
      published since recent Cochrane and systematic reviews on this topic.
      Conclusions: Contraceptive use is safer than pregnancy, especially for obese
      women who have increased pregnancy risks. Baseline health is compromised by
      obesity, but contraceptive risks remain low. Long-acting, reversible
      contraceptive methods offer superior effectiveness, minimal risk, and numerous
      noncontraceptive benefits across body mass index groups. No substantial evidence
      supports ineffectiveness of any method in obese women except oral emergency
      contraception and the patch. Pharmacokinetic changes of obesity associated with
      other oral methods do not seem to result in clinically significant declines in
      effectiveness. Future contraceptive efficacy studies should include obese women
      to better discuss their contraceptive needs. Relevance: This review is beneficial
      for all providers caring for reproductive-aged women wanting to avoid unintended
      pregnancy.

PMID- 29368792
TI  - Deformation behaviour of aged coronal dentin.
AB  - OBJECTIVE: This study aimed to identify the changes in the time-dependent
      deformation response of coronal dentin with ageing and its relationship with
      changes in chemical composition. BACKGROUND: The structural behaviour of dentin
      with ageing is affected by changes in the density and diameter of its dentinal
      tubules (ie porosity), as well as changes in chemical composition throughout the
      tooth. However, little is known about the time-dependent deformation behaviour of
      aged dentin and the importance of its hierarchical structure and variations in
      chemical composition. MATERIALS AND METHODS: The spherical indentation response
      of aged coronal dentin was analysed in the outer, middle and inner regions, and
      its time-dependent deformation response was modelled in terms of its
      microstructure and chemical composition using a model recently proposed for young
      dentin. RESULTS: The viscous deformation behaviour of aged dentin followed a
      power-law response with a decrease in the stress exponent when compared to young
      dentin. These results can be explained by cross-linking of the collagen present
      in the tissue. CONCLUSION: A decrease in the deformation ability of aged dentin
      was found. This behaviour could be a result of a dissolution process and
      reprecipitation of the minerals present in intertubular dentin into the dentinal
      tubules.

PMID- 29368793
TI  - Different aberrant expression pattern of immune checkpoint receptors in patients
      with PTCL and NK/T-CL.
AB  - AIM: To better understand the T-cell immunodeficiency status in patients with
      peripheral T-cell lymphomas (PTCLs) and NK/T-cell lymphomas (NK/T-CLs), the T
      cell inhibitory receptors expression pattern was investigated. METHODS: The
      expression levels of programmed death 1 (PD-1), cytotoxic T lymphocyte-associated
      antigen 4 (CTLA-4), B/T lymphocyte attenuator (BTLA), lymphocyte-activation gene
      3 (LAG-3), T-cell immunoglobulin-3 (TIM-3), T-cell immunoglobulin and ITIM domain
      (TIGIT) genes were detected in peripheral blood mononuclear cells (PBMCs) from
      patients and healthy volunteers by quantitative real-time-PCR, the correlation
      between different gene expression levels was analyzed. RESULTS: Significantly
      higher expression of PD-1, CTLA-4, BTLA, LAG-3, TIM-3 and TIGIT can be observed
      as a common characteristic in patients with PTCL or NK/T-CL. However, the
      coexpression pattern seemed different between subtypes. Their overexpression is
      also related to disease progression stage. CONCLUSION: We first characterized the
      expression pattern of six T-cell inhibitory receptor genes in PTCL and NK/T-CL,
      which might work as immune biomarkers for evaluation the immunosuppression status
      and help to establish the precision targets of immunotherapy.

PMID- 29368794
TI  - Amplification of FRS2 in atypical lipomatous tumour/well-differentiated
      liposarcoma and de-differentiated liposarcoma: a clinicopathological and genetic
      study of 146 cases.
AB  - AIMS: The aim of this study was to evaluate the frequency of FRS2 amplification
      and its relationship with the clinicopathological features of atypical lipomatous
      tumour (ALT)/well-differentiated liposarcoma (WDL)/de-differentiated liposarcoma
      (DDL). METHODS AND RESULTS: FRS2 and MDM2 fluorescence in-situ hybridisation
      (FISH) was performed on 146 tumours (70 ALT/WDLs and 76 DDLs). One hundred and
      eight control samples were included for FRS2 analysis. FRS2 amplification was
      detected in 136 of 146 (93.2%) ALT/WDL/DDLs, including 63 ALT/WDLs and 73 DDLs. A
      higher FRS2/CEP12 ratio was observed in DDLs than in ALT/WDLs (P = 0.0005). The
      FRS2/CEP12 ratio of peripheral tumours was lower than that of central tumours (P
      = 0.00004). All the ALT/WDL/DDLs showed MDM2 amplification (100%). The MDM2+
      /FRS2- series included seven ALT/WDLs and three DDLs. Four of seven (57.1%) MDM2+
      /FRS2- ALT/WDLs occurred in peripheral sites, slightly higher than the percentage
      of MDM2+ /FRS2+ ALT/WDLs (28 of 63, 44.4%). All the three MDM2+ /FRS2- DDLs
      (100%) were peripheral tumours, a much higher proportion than that of MDM2+
      /FRS2+ DDLs (10 of 73, 13.7%). A high percentage of homologous pleomorphic
      liposarcoma-like DDLs (two of three) were observed in the MDM2+ /FRS2- group. In
      the control group all the parosteal osteosarcomas (five of five, 100%) were FRS2
      amplified, whereas the remaining 103 samples were FRS2 non-amplified.
      CONCLUSIONS: These findings suggest that FRS2 is amplified consistently in
      ALT/WDL/DDLs and offer another avenue for the investigation of the biology of
      this tumour group. MDM2+ /FRS2- cases seem to be associated with certain
      clinicopathological features, and further investigation is needed.

PMID- 29368795
TI  - Intrauterine insemination versus intracervical insemination in donor sperm
      treatment.
AB  - BACKGROUND: The first-line treatment in donor sperm treatment consists of
      inseminations that can be done by intrauterine insemination (IUI) or by
      intracervical insemination (ICI). OBJECTIVES: To compare the effectiveness and
      safety of intrauterine insemination (IUI) and intracervical insemination (ICI) in
      women who start donor sperm treatment. SEARCH METHODS: We searched the Cochrane
      Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase,
      PsycINFO, CINAHL in October 2016, checked references of relevant studies, and
      contacted study authors and experts in the field to identify additional studies.
      We searched PubMed, Google Scholar, the Grey literature, and five trials
      registers on 15 December 2017. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) reporting on IUI versus ICI in natural cycles or with
      ovarian stimulation, and RCTs comparing different cointerventions in IUI and ICI.
      We included cross-over studies if pre-cross-over data were available. DATA
      COLLECTION AND ANALYSIS: We used standard methodological procedures recommended
      by Cochrane. We collected data on primary outcomes of live birth and multiple
      pregnancy rates, and on secondary outcomes of clinical pregnancy, miscarriage,
      and cancellation rates. MAIN RESULTS: We included six RCTs (708 women analysed)
      on ICI and IUI in donor sperm treatment. Two studies compared IUI and ICI in
      natural cycles, two studies compared IUI and ICI in gonadotrophin-stimulated
      cycles, and two studies compared timing of IUI and ICI. There was very low
      quality evidence; the main limitations were risk of bias due to poor reporting of
      study methods, and serious imprecision.IUI versus ICI in natural cyclesThere was
      insufficient evidence to determine whether there was any clear difference in live
      birth rate between IUI and ICI in natural cycles (odds ratio (OR) 3.24, 95%
      confidence interval (CI) 0.12 to 87.13; 1 RCT, 26 women; very low-quality
      evidence). There was only one live birth in this study (in the IUI group). IUI
      resulted in higher clinical pregnancy rates (OR 6.18, 95% CI 1.91 to 20.03; 2
      RCTs, 76 women; I2 = 48%; very low-quality evidence).No multiple pregnancies or
      miscarriages occurred in this study.IUI versus ICI in gonadotrophin-stimulated
      cyclesThere was insufficient evidence to determine whether there was any clear
      difference in live birth rate between IUI and ICI in gonadotrophin-stimulated
      cycles (OR 2.55, 95% CI 0.72 to 8.96; 1 RCT, 43 women; very low-quality
      evidence). This suggested that if the chance of a live birth following ICI in
      gonadotrophin-stimulated cycles was assumed to be 30%, the chance following IUI
      in gonadotrophin-stimulated cycles would be between 24% and 80%. IUI may result
      in higher clinical pregnancy rates than ICI (OR 2.83, 95% CI 1.38 to 5.78; 2
      RCTs, 131 women; I2 = 0%; very low-quality evidence). IUI may be associated with
      higher multiple pregnancy rates than ICI (OR 2.77, 95% CI 1.00 to 7.69; 2 RCTs,
      131 women; I2 = 0%; very low-quality evidence). This suggested that if the risk
      of multiple pregnancy following ICI in gonadotrophin-stimulated cycles was
      assumed to be 10%, the risk following IUI would be between 10% and 46%.We found
      insufficient evidence to determine whether there was any clear difference between
      the groups in miscarriage rates in gonadotrophin-stimulated cycles (OR 1.97, 95%
      CI 0.43 to 9.04; 2 RCTs, overall 67 pregnancies; I2 = 50%; very low-quality
      evidence).Timing of IUI and ICIWe found no studies that reported on live birth
      rates.We found a higher clinical pregnancy rate when IUI was timed one day after
      a rise in blood levels of luteinising hormone (LH) compared to IUI two days after
      a rise in blood levels of LH (OR 2.00, 95% CI 1.14 to 3.53; 1 RCT, 351 women; low
      quality evidence). We found insufficient evidence to determine whether there was
      any clear difference in clinical pregnancy rates between ICI timed after a rise
      in urinary levels of LH versus a rise in basal temperature plus cervical mucus
      scores (OR 1.31, 95% CI 0.42 to 4.11; 1 RCT, 56 women; very low-quality
      evidence).Neither of these studies reported multiple pregnancy or miscarriage
      rates as outcomes. AUTHORS' CONCLUSIONS: There was insufficient evidence to
      determine whether there was a clear difference in live birth rates between IUI
      and ICI in natural or gonadotrophin-stimulated cycles in women who started with
      donor sperm treatment. There was insufficient evidence available for the effect
      of timing of IUI or ICI on live birth rates. Very low-quality data suggested that
      in gonadotrophin-stimulated cycles, ICI may be associated with a higher clinical
      pregnancy rate than IUI, but also with a higher risk of multiple pregnancy rate.
      We concluded that the current evidence was too limited to choose between IUI or
      ICI, in natural cycles or with ovarian stimulation, in donor sperm treatment.

PMID- 29368797
TI  - A two-path model of auditory modulation detection using temporal fine structure
      and envelope cues.
AB  - A model using temporal-envelope cues was previously developed to explain
      perceptual interference effects between amplitude modulation and frequency
      modulation (FM). As that model could not accurately predict FM sensitivity and
      the interference effects, temporal fine structure (TFS) cues were added to the
      model. Thus, following the initial stage of the model consisting of a linear
      filter bank simulating cochlear filtering, processing was split into an 'envelope
      path' based on envelope power cues and a 'TFS path' based on a measure of the
      distribution of time intervals between successive zero-crossings. This yielded
      independent detectability indices for envelope and TFS cues, which were optimally
      combined to produce a single decision statistic. Independent internal noises in
      the envelope and TFS paths were adjusted to match the data. Simulations indicate
      that TFS cues are required to account for FM data for young normal-hearing
      listeners and that TFS processing is impaired for both older normal-hearing and
      hearing-impaired listeners. The role of TFS was further assessed by relating the
      monaural FM sensitivity to measures of interaural phase difference, commonly
      assumed to rely on binaural TFS sensitivity. The model demonstrates that binaural
      TFS sensitivity is considerably lower than monaural TFS sensitivity. Similar to
      FM thresholds, interaural phase difference sensitivity declined with age and
      hearing loss, although higher degradations were observed in binaural temporal
      processing compared to monaural processing. Overall, this model provides a novel
      tool to explore the mechanisms involved in FM processing in the normal auditory
      system and the degradations in FM sensitivity with ageing and hearing loss.

PMID- 29368796
TI  - Survey of 5 mm small-field output factor measurements in Australia.
AB  - The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) held a
      comparison exercise in April 2016 where participants came to ARPANSA and measured
      the output factor of a nominal 5 mm cone attached to the ARPANSA Elekta Synergy
      (Elekta, Crawley, UK) linear accelerator. The goal of the exercise was to compare
      the consistency and methods used by independent medical physicists in measuring
      small-field output factors. ARPANSA provided a three-dimensional scanning tank
      for detector setup and positioning, but the participants were required to measure
      the output factor with their own detectors. No information regarding output
      factors previously measured was supplied to participants to make each result as
      independent as possible. Fifteen groups travelled to ARPANSA bringing a wide
      range of detectors and methods. A total of 30 measurements of the output factor
      were made. The standard deviation of the measurements (excluding one expected
      outlier from an uncorrected ionization chamber measurement) was 3.6%. The results
      provide an insight into the consistency of small-field dosimetry being performed
      in Australia and New Zealand at the present time.

PMID- 29368798
TI  - Chloride intracellular channel 1 (CLIC1) contributes to modulation of cyclic AMP
      activated whole-cell chloride currents in human bronchial epithelial cells.
AB  - Chloride channels are known to play critical physiological roles in many cell
      types. Here, we describe the expression of anion channels using RNA Seq in
      primary cultures of human bronchial epithelial cells (hBECs). Chloride
      intracellular channel (CLIC) family members were the most abundant chloride
      channel transcripts, and CLIC1 showed the highest level of expression. In
      addition, we characterize the chloride currents in hBECs and determine how
      inhibition of CLIC1 via pharmacological and molecular approaches impacts these.
      We demonstrate that CLIC1 is able to modulate cyclic AMP-induced chloride
      currents and suggest that CLIC1 modulation could be important for chloride
      homeostasis in this cell type.

PMID- 29368799
TI  - The influence of pulmonary vascular pressures on lung diffusing capacity during
      incremental exercise in healthy aging.
AB  - Alveolar-capillary surface area for pulmonary gas exchange falls with aging,
      causing a reduction in lung diffusing capacity for carbon monoxide (DLCO).
      However, during exercise additional factors may influence DLCO, including
      pulmonary blood flow and pulmonary vascular pressures. First, we sought to
      determine the age-dependent effect of incremental exercise on pulmonary vascular
      pressures and DLCO. We also aimed to investigate the dependence of DLCO on
      pulmonary vascular pressures during exercise via sildenafil administration to
      reduce pulmonary smooth muscle tone. Nine younger (27 +/- 4 years) and nine older
      (70 +/- 3 years) healthy subjects performed seven 5-min exercise stages at rest,
      0 (unloaded), 10, 15, 30, 50, and 70% of peak workload before and after
      sildenafil. DLCO, cardiac output (Q), and pulmonary artery and wedge pressure
      (mPAP and mPCWP; subset of participants) were collected at each stage. mPAP was
      higher (P = 0.029) and DLCO was lower (P = 0.009) throughout exercise in older
      adults; however, the rate of rise in mPAP and DLCO with increasing Q was not
      different. A reduction in pulmonary smooth muscle tone via sildenafil
      administration reduced mPAP, mPCWP, and the transpulmonary gradient (TPG = mPAP
      mPCWP) in younger and older subjects (P < 0.001). DLCO was reduced following the
      reduction in mPAP and TPG, regardless of age (P < 0.001). In conclusion, older
      adults successfully adapt to age-dependent alterations in mPAP and DLCO.
      Furthermore, DLCO is dependent on pulmonary vascular pressures, likely to
      maintain adequate pulmonary capillary recruitment. The rise in pulmonary artery
      pressure with aging may be required to combat pulmonary vascular remodeling and
      maintain lung diffusing capacity, particularly during exercise.

PMID- 29368800
TI  - Food addiction and associations with mental health symptoms: a systematic review
      with meta-analysis.
AB  - BACKGROUND: The present study systematically reviewed the literature aiming to
      determine the relationships between food addiction, as measured by the Yale Food
      Addiction Scale (YFAS), and mental health symptoms. METHODS: Nine databases were
      searched using keywords. Studies were included if they reported: (i) YFAS
      diagnosis or symptom score and (ii) a mental health outcome, as well as the
      association between (i) and (ii). In total, 51 studies were included. RESULTS:
      Through meta-analysis, the mean prevalence of food addiction diagnosis was 16.2%,
      with an average of 3.3 (range 2.85-3.92) food addiction symptoms being reported.
      Subanalyses revealed that the mean number of food addiction symptoms in
      populations seeking treatment for weight loss was 3.01 (range 2.65-3.37) and this
      was higher in groups with disordered eating (mean 5.2 3.6-6.7). Significant
      positive correlations were found between food addiction and binge eating [mean r
      = 0.602 (0.557-0.643), P < 0.05], depression, anxiety and food addiction [mean r
      = 0.459 (0.358-0.550), r = 0.483 (0.228-0.676), P < 0.05, respectively].
      CONCLUSIONS: A significant, positive relationship exists between food addiction
      and mental health symptoms, although the results of the present study highlight
      the complexity of this relationship.

PMID- 29368801
TI  - Adaptive immune responses are altered in adult mice following neonatal hyperoxia.
AB  - Premature infants with bronchopulmonary dysplasia (BPD), are at risk for frequent
      respiratory infections and reduced pulmonary function. We studied whether
      neonatal hyperoxia disrupts adaptive immune responses in adult mice, contributing
      to higher respiratory-related morbidities seen in these infants. Newborn mice
      litters were randomized at 3 days to 85% O2 or room air (RA) for 12 days. Whole
      lung mRNA was isolated in both the groups at 2 weeks and 3 months. Gene
      expression for T-cell and B-cell adaptive immune response was performed by real
      time PCR and qRT-PCR; protein expression (p21, IL4, IL10, IL27, cd4) was
      performed by enzyme immunoassay along with p21 immunohistochemistry. Hyperoxia
      increased expression of p21 and decreased expression of 19 genes representing T/B
      cell activation by >= fourfold; three of them significantly (Rag1, Cd1d1, Cd28)
      compared to the RA group at 2 weeks. Despite RA recovery, the expression of
      IFNgamma, IL27, and CD40 was significantly reduced at 3 months in the hyperoxia
      group. Expression of p21 was significantly higher and IL27 protein lower at 2
      weeks following hyperoxia. Adult mice exposed to neonatal hyperoxia had lower IL4
      and IL10 in the lung at 3 months. Adaptive immune responses are developmentally
      regulated and neonatal hyperoxia suppresses expression of genes involved in T-/B
      cell activation with continued alterations in gene expression at 3 months.
      Dysfunction of adaptive immune responses increases the risk for susceptibility to
      infection in premature infants.

PMID- 29368802
TI  - Dietary nitrate-induced increases in human muscle power: high versus low
      responders.
AB  - Maximal neuromuscular power is an important determinant of athletic performance
      and also quality of life, independence, and perhaps even mortality in patient
      populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide
      (NO), improves muscle power in some, but not all, subjects. The present
      investigation was designed to identify factors contributing to this
      interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of
      age and weighing 52.1-114.9 kg were studied using a randomized, double-blind,
      placebo-controlled, crossover design. Subjects were tested 2 h after ingesting
      beetroot juice (BRJ) either containing or devoid of 12.3 +/- 0.8 mmol of NO3- .
      Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability
      and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were
      determined via isokinetic dynamometry. On average, dietary NO3- increased (P <
      0.05) Pmax by 4.4 +/- 8.1%. Individual changes, however, ranged from -9.6 to
      +26.8%. This interindividual variability was not significantly correlated with
      age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body
      composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle
      fiber type distribution). In contrast, the relative increase in Pmax was
      significantly correlated (r = 0.60; P < 0.01) with the relative increase in
      plasma NO2- concentration. In multivariable analysis female sex also tended (P =
      0.08) to be associated with a greater increase in Pmax. We conclude that the
      magnitude of the dietary NO3- -induced increase in muscle power is dependent upon
      the magnitude of the resulting increase in plasma NO2- and possibly female sex.

PMID- 29368803
TI  - Early time course of variation in coelomic fluid ionic concentrations in sea
      urchins abruptly exposed to hypo- and hyper-osmotic salinity challenges: Role of
      size and cross-section area of test holes.
AB  - Echinoderms are restricted to the marine environment and are osmoconformer
      invertebrates. However, some species live in unstable environments. Especially
      those species, and those of larger body size, tend to show variable, albeit
      transient, ionic gradients between their coelomic fluid and external seawater. In
      order to further examine how sea urchin size relates to apparent ionic
      permeability of their body wall/epithelia, specimens of Echinometra lucunter,
      Lytechinus variegatus, Paracentrotus gaimardi, and Arbacia lixula-A. lixula of
      two distinct populations, Rio de Janeiro and Santa Catarina-were abruptly
      transferred from 35 psu to either 25 or 45 psu. Sodium, chloride, magnesium, and
      potassium concentrations were assayed in their coelomic fluids after 0, 1, 2, and
      3 hr of exposure. Relative area of putative permeable (i.e., cross section areas
      of soft tissues, or test holes) surfaces (PPS) was estimated in empty tests as
      the sum of the peristomial area (oral hole in the empty test) and the total cross
      section area of ambulacral holes, divided by the total volume (TV) of the test.
      L. variegatus and E. lucunter, the largest species, had PPS/TV values similar to
      that of the much smaller P. gaimardi. A. lixula was the "most putatively
      permeable and conformer" among them all, especially urchins from the Santa
      Catarina population. Internal ionic levels equilibrated faster with external
      water in 45 than in 25, and differences among ions were observed. Body size is
      relevant, among many other factors, to aid conformers such as sea urchins to
      dwell in intertidal unstable habitats.

PMID- 29368804
TI  - Endomycorrhizae and rhizobial Nod factors both require SYM8 to induce the
      expression of the early nodulin genes PsENOD5 and PsENOD12A.
AB  - We report here that the pea early nodulin genes PsENOD5 and PsENOD12A are induced
      during the interaction of pea roots and the endomycorrhizal fungus Gigaspora
      margarita. Using the pea nodulation mutant Sparkle-R25, which is mutated in SYM8,
      it is shown that SYM8 is essential for the induction of PsENOD5 and PsENOD12Ain
      pea roots interacting either with Rhizobium or the endomycorrhizal fungus
      Gigaspora margarita. Our results suggest that mycorrhizal signals activate a
      signal transduction cascade sharing at least one common step with the Nod factor
      activated signal transduction cascade.

PMID- 29368805
TI  - Post-transcriptional silencing of chalcone synthase in petunia using a
      geminivirus-based episomal vector.
AB  - A vector that produces DNA replicons (multicopy plant episomes) was constructed
      using elements of the geminivirus tobacco yellow dwarf virus (TYDV). All plant
      cells contain an integrated chromosomal T-DNA copy of the TYDV elements that
      provides a template for the production of episomes in the cell nucleus.
      Transgenic Petunia hybrida plants containing a CaMV 35S promoter-driven chalcone
      synthase A (ChsA) gene cloned into the episomal vector produced flowers with a
      white-spotted phenotype at high frequency. The spots were found at random
      locations in the petals and occurred in corresponding positions in both the upper
      and lower epidermis, indicating that the spots were non-clonal. The spotted
      phenotype was somatically stable and was inherited through meiosis. In white
      spotted flower tissue, steady-state ChsA mRNA levels were downregulated but rates
      of RNA transcription were unaffected, suggesting that the phenotype resulted from
      post-transcriptional gene silencing of the endogenous and episomal ChsA genes.
      Increases in both the frequency and extent of gene silencing in flowers
      correlated with increases in episome copy number in mature flowers, flower buds
      and young and fully expanded leaves. Relatively small increases in episome copy
      number (less than threefold) appeared sufficient to trigger the gene-silenced
      phenotype.

PMID- 29368806
TI  - Immediate early induction of mRNAs for ethylene-responsive transcription factors
      in tobacco leaf strips after cutting.
AB  - To investigate the functional relationship between the expression of genes for
      ethylene-responsive transcription factors (ERFs) and the expression of ethylene
      responsive genes, we examined the expression of genes for ERFs and the expression
      of a reporter gene in transgenic tobacco that carried a gene for beta
      glucuronidase (GUS) under the control of the ethylene-responsive element, which
      includes four copies of the 11-bp consensus sequence (designated the GCC-box,
      TAAGAGCCGCC). In strips of leaves of transgenic tobacco, the GCC-box-mediated
      expression of the reporter gene was induced in response to treatment with
      ethylene. We also observed the ethylene-independent immediate early induction of
      the synthesis of mRNAs for ERFs in wounded leaves and the enhancement of this
      induction by cycloheximide (CHX). Since CHX suppressed the induction of mRNAs for
      chitinase and GUS by ethylene, protein synthesis de novo was required for
      induction of the ethylene-dependent GCC-box-mediated transcription of genes. In
      contrast, the enhancement by CHX of the wound-induced expression of ERFs
      suggested that no synthesis of new proteins was required for the wounding signal
      transduction leading to rapid expression of ERFs. Methyl jasmonate did not
      stimulate the wounding-responsive accumulation of ERF mRNAs, but it reduced such
      accumulation of mRNAs for ERF1, ERF2, ERF4 and the ethylene-dependent GCC-box
      mediated transcription of the reporter gene. Thus, the immediate early induction
      of the expression of genes for ERFs in strips of tobacco leaves appears to be a
      novel type of wound-responsive activation of transcription. These results
      suggested that the expression of ERFs was not sufficient for activation of the
      GCC-box-mediated transcription but the expression of ERF1, ERF2 and ERF4, and
      that conversion of these ERFs by ethylene to their active form might be crucial
      for the GCC-box-mediated activation of the transcription of defense genes.

PMID- 29368807
TI  - The control of source to sink carbon flux during tuber development in potato.
AB  - We have used top-down metabolic control analysis to investigate the control of
      carbon flux through potato (Solanum tuberosum) plants during tuberisation. The
      metabolism of the potato plant was divided into two blocks of reactions (the
      source and sink blocks) that communicate through the leaf apoplastic sucrose
      pool. Flux was measured as the transfer of 14 C from CO2 to the tuber. Flux and
      apoplastic sucrose concentration were varied either by changing the light
      intensity or using transgenic manipulations that specifically affect the source
      or sink blocks, and elasticity coefficients were measured. We have provided
      evidence in support of our assumption that apoplastic sucrose is the only
      communicating metabolite between the source and sink blocks. The elasticity
      coefficients were used to calculate the flux control coefficients of the source
      and sink blocks, which were 0.8 and 0.2, respectively. This work suggests that
      the best strategy for the manipulation of tuber yield in potato will involve
      increases in photosynthetic capacity, rather than sink metabolism.

PMID- 29368808
TI  - A mutant in Lycopersicon esculentum Mill. with highly reduced VA mycorrhizal
      colonization: isolation and preliminary characterisation.
AB  - This paper reports the successful isolation and preliminary characterisation of a
      mutant of Lycopersicon esculentum Mill. with highly reduced vesicular-arbuscular
      (VA) mycorrhizal colonization. The mutation is recessive and has been designated
      rmc . Colonization by G. mosseae is characterised by poor development of external
      mycelium and a few abnormal appressoria. Vesicles were never formed by this
      fungus in association with the mutant. Gi. margarita formed large amounts of
      external mycelium, complex branched structures and occasional auxiliary cells.
      Small amounts of internal colonization also occurred. Laser scanning confocal
      microscopy (LSCM) gave a clear picture of the differences in development of G.
      intraradices and Gi. margarita in mutant and wild-type roots and confirmed that
      the fungus is restricted to the root surface of the mutants. The amenability of
      tomato for molecular genetic characterisation should enable us to map and clone
      the mutated gene, and thus identify one of the biochemical bases for inability to
      establish a normal mycorrhizal symbiosis. The mutant represents a key advance in
      molecular research on VA mycorrhizal symbiosis.

PMID- 29368809
TI  - Transcriptional and post-transcriptional processes regulate gene expression in
      oxygen-deprived roots of maize.
AB  - To investigate the regulation of gene expression in maize ( Zea mays L.) in
      response to oxygen deprivation (flooding), we quantitated run-on transcription in
      isolated nuclei, steady-state mRNA accumulation and mRNA loading with ribosomes
      for seven genes that encode proteins synthesized predominantly in oxygen-deprived
      roots (anaerobic polypeptides) and seven genes that encode proteins synthesized
      in aerobic roots (aerobic polypeptides). Run-on transcription of anaerobic
      polypeptide genes was induced in response to oxygen deprivation and run-on
      transcription of the aerobic polypeptide genes continued during the stress
      treatment. The increased accumulation of mRNAs that encode anaerobic polypeptides
      occurred concomitant with the induction of gene transcription and efficient
      association of these mRNAs with large polysomes. The steady-state accumulation of
      aerobic polypeptide mRNAs was within twofold of aerobic levels and in a number of
      cases fewer ribosomes were loaded per transcript. These results demonstrate that
      selected synthesis of anaerobic polypeptides involves transcriptional as well as
      significant post-transcriptional regulation of gene expression. The repression of
      synthesis of many aerobic polypeptides occurs without interruption of gene
      transcription and is due to translational regulation and possibly the
      sequestration of mRNAs on mRNPs. Ribosome loading patterns indicated that this
      translational control occurs at both initiation and post-initiation phases in a
      message-specific manner.

PMID- 29368810
TI  - A transgene with repeated DNA causes high frequency, post-transcriptional
      suppression of ACC-oxidase gene expression in tomato.
AB  - Gene silencing with sense genes is an important method for down-regulating the
      expression of endogenous plant genes, but the frequency of silencing is
      unpredictable. Fifteen per cent of tomato plants transformed with a 35S-ACC
      oxidase ( ACO 1) sense gene had reduced ACC-oxidase activity. However, 96% of
      plants transformed with an ACC-oxidase sense gene, containing two additional
      upstream inverted copies of its 5' untranslated region, exhibited reduced ACC
      oxidase activity compared to wild-type plants. In the three plants chosen for
      analysis, there were substantially reduced amounts of both endogenous and
      transgenic ACO RNA, indicating that this was an example of co-suppression.
      Ribonuclease protection assays using probes spanning intron-exon borders showed
      that the reduced accumulation of endogenous ACO mRNA occurred post
      transcriptionally since the abundance of unprocessed transcripts was not
      affected. The ACO1 transgene with the repeated 5'UTR also strongly inhibited the
      accumulation of RNA from the related ACO 2 gene in flowers, although there is
      little homology between the 5'UTRs of ACO 1 and ACO 2. These results indicate
      that although repeated DNA in a transgene greatly enhances the probability of
      gene silencing of an endogenous gene, it also involves generation of a trans 
      acting silencing signal produced, at least partly, from sequences external to the
      repeat.

PMID- 29368812
TI  - Distribution of TMV movement protein in single living protoplasts immobilized in
      agarose.
AB  - Recent studies of the tobacco mosaic virus (TMV) P30 movement protein (MP) fused
      with green fluorescent protein (GFP) during TMV infection described the
      involvement of elements of the cytoskeleton and components of the endoplasmic
      reticulum (ER) in the intracellular trafficking of MP:GFP from the sites of
      synthesis in the cytoplasm to plasmodesmata. To examine in real-time the pattern
      of synthesis, accumulation and degradation of MP:GFP, we developed a method to
      immobilize protoplasts in agarose such that they are maintained alive for
      extended periods of time. The pattern of MP:GFP accumulation in single living
      protoplasts visualized by confocal laser scanning microscopy (CLSM) was parallel
      to that previously described in a population of protoplasts harvested at
      different times post-infection. Additionally, a network of weakly fluorescent
      filaments, which are apparently different from microtubules, was observed to
      surround the nucleus and these filaments were associated with fluorescent bodies
      (previously identified as ER-derived structures). Later in infection, the
      fluorescent bodies increased in size and coalesced to form larger structures that
      accumulated near the periphery of the cells while highly fluorescent non-cortical
      filaments were observed distributed in the cytoplasm. The putative involvement of
      these filaments in targeting the fluorescent bodies to the periphery of the cell
      is discussed. Studies of single, embedded protoplasts make it possible to observe
      changes in amount and subcellular localization of viral and other proteins.

PMID- 29368813
TI  - Selective noradrenaline reuptake inhibitors for schizophrenia.
AB  - BACKGROUND: Schizophrenia is frequently a chronic and disabling illness with a
      heterogeneous range of symptoms. The positive symptoms usually respond to
      antipsychotics but the cognitive and negative symptoms of schizophrenia are
      difficult to treat with conventional antipsychotics and significantly impact on
      quality of life and social outcomes. Selective noradrenaline reuptake inhibitors
      (NRIs) increase prefrontal dopamine and noradrenaline levels without
      significantly affecting subcortical dopamine levels, making them an attractive
      candidate for treating cognitive and negative symptoms. OBJECTIVES: To
      investigate the effects of selective noradrenaline reuptake inhibitors (NRIs),
      compared with a placebo or control treatment, for people with schizophrenia.
      SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register
      (up to 7 February 2017) which is based on regular searches of MEDLINE, Embase,
      CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. There
      are no language, date, document type, or publication status limitation for
      inclusion of records into the register. We inspected references of all included
      studies for further relevant studies. SELECTION CRITERIA: We included randomised
      controlled trials (RCTs) comparing NRIs with either a control treatment or
      placebo for people with schizophrenia or related disorders (such as
      schizoaffective disorder) by any means of diagnosis. We included trials that met
      our selection criteria and provided useable information. DATA COLLECTION AND
      ANALYSIS: We independently inspected all citations from searches, identified
      relevant abstracts, and independently extracted data from all included studies.
      For binary data we calculated risk ratio (RR), for continuous data we calculated
      mean difference (MD), and for cognitive outcomes we derived standardised mean
      difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a
      random-effects model. We assessed risk of bias for the included studies and used
      the GRADE approach to produce a 'Summary of findings' table which included our
      prespecified main outcomes of interest. MAIN RESULTS: Searching identified 113
      records. We obtained the full text of 48 of these records for closer inspection.
      Sixteen trials, randomising a total of 919 participants are included. The
      majority of trials included adults with schizophrenia or similar illness who were
      inpatients, and while they were poorly characterised, most appeared to include
      patients with a chronic presentation. The intervention NRI in nine of the 16
      trials was reboxetine, with atomoxetine and viloxazine used in the remaining
      trials. 14 trials compared NRIs with placebo. Only two trials provided data to
      compare NRIs against an active control and both compared reboxetine to citalopram
      but at 4 weeks and 24 weeks respectively so they could not be combined in a meta
      analysis.One trial was described as 'open' and we considered it to be at high
      risk of bias for randomisation and blinding, three trials were at high risk of
      bias for attrition, six for reporting, and two for other sources of bias. Our
      main outcomes of interest were significant response or improvement in
      positive/negative mental state, global state and cognitive functioning, average
      cognitive functioning scores, significant response or improvement in quality of
      life and incidence of nausea. All data for main outcomes were short term.NRIs
      versus placeboMental state results showed significantly greater rates of
      improvement in negative symptoms scores (1 RCT, n = 50; RR 3.17, 95% CI 1.52 to
      6.58; very low quality evidence) with NRIs on the PANSS negative. No data were
      reported for significant response or improvement in positive symptoms, but
      average endpoint PANSS positive scores were available and showed no difference
      between NRIs and placebo (5 RCTs, n = 294; MD -0.16, 95% CI -0.96 to 0.63; low
      quality evidence). Improvement in clinical global status was similar between
      groups (1 RCT, n = 28; RR 0.99, 95% CI 0.45 to 2.20; very low quality evidence).
      Significant response or improvement in cognitive functioning data were not
      reported. Average composite cognitive scores showed no difference between NRIs
      and placebo (4 RCTs, n = 180; SMD 0.04, 95% CI -0.28 to 0.36; low-quality
      evidence). Significant response or improvement in quality of life data were not
      reported, however average endpoint scores from the GQOLI-74 were reported. Those
      receiving NRIs had better quality of life scores compared to placebo (1 RCT, n =
      114; MD 9.36, 95% CI 7.89 to 10.83; very low quality evidence). All-cause
      withdrawals did not differ between the treatment groups (8 RCTs, n = 401, RR 0.94
      95% CI 0.63 to 1.39; moderate-quality evidence). Rates of nausea were not greater
      with NRIs (3 RCTs, n = 176; RR 0.49, 95% CI 0.10 to 2.41; low-quality evidence).
      AUTHORS' CONCLUSIONS: Our results provide tentative very low quality evidence
      that compared to placebo, NRIs (specifically reboxetine) may have a benefit on
      the negative symptoms of schizophrenia. Limited evidence also suggests that NRIs
      have no effect on the positive symptoms of schizophrenia or cognitive
      functioning. NRIs appear generally well tolerated with no real differences in
      adverse effects such as nausea noted between NRIs and placebo. However, these
      results are based on short-term follow-up and are poor quality - there is need
      for more good-quality evidence. A large RCT of reboxetine over a longer period of
      time, focusing specifically on negative and cognitive symptoms as well as more
      detailed and comprehensive reporting of outcomes, including adverse events, is
      required.

PMID- 29368815
TI  - Telomere erosion varies with sex and age at immune challenge but not with
      maternal antibodies in pigeons.
AB  - Conditions experienced early in life have profound impact on adult fitness, and
      telomere erosion could be a key mechanism in this process. In particular, early
      exposure to parasites is a frequent phenomenon in young vertebrates, which is
      associated with several short- and long-term costs such as telomere erosion.
      However, the timing of exposure to parasites during ontogeny and maternal
      antibodies can strongly modulate the costs of immunity, and could differentially
      affect telomere erosion. Here, we compared the effects of an early or late immune
      challenge on telomere erosion rate in male and female young feral pigeons
      (Columba livia) having received or not maternal antibodies. More specifically, we
      tested whether (i) early or late injections of antigens had different effects on
      nestling telomere erosion rate, (ii) whether this effect was different between
      male and female nestlings, and (iii) whether maternal antibodies could modulate
      telomere erosion rate. Our results show an interaction between sex and age at
      injection. Late-injected nestlings (injected at 14 days of age) had an
      accelerated erosion rate compared with the early-injected nestlings (injected at
      3 days of age), and this effect was higher in females compared with the males.
      However, we did not find any effect of maternal antibodies on telomere erosion
      rate. These results suggest that the age at which an immune challenge occurs is
      important for telomere erosion and that sex-specific approaches are needed to
      better understand the short-term and long-term costs of parasite exposure in
      young vertebrates.

PMID- 29368814
TI  - Synchronization of intrinsic 0.1-Hz blood-oxygen-level-dependent oscillations in
      amygdala and prefrontal cortex in subjects with increased state anxiety.
AB  - Low-frequency oscillations with a dominant frequency at 0.1 Hz are one of the
      most influential intrinsic blood-oxygen-level-dependent (BOLD) signals. This
      raises the question if vascular BOLD oscillations (originating from blood flow in
      the brain) and intrinsic slow neural activity fluctuations (neural BOLD
      oscillations) can be differentiated. In this study, we report on two different
      approaches: first, on computing the phase-locking value in the frequency band
      0.07-0.13 Hz between heart beat-to-beat interval (RRI) and BOLD oscillations and
      second, between multiple BOLD oscillations (functional connectivity) in four
      resting states in 23 scanner-naive, anxious healthy subjects. The first method
      revealed that vascular 0.1-Hz BOLD oscillations preceded those in RRI signals by
      1.7 +/- 0.6 s and neural BOLD oscillations lagged RRI oscillations by 0.8 +/- 0.5
      s. Together, vascular BOLD oscillations preceded neural BOLD oscillations by ~90
      degrees  or ~2.5 s. To verify this discrimination, connectivity patterns of
      neural and vascular 0.1-Hz BOLD oscillations were compared in 26 regions involved
      in processing of emotions. Neural BOLD oscillations revealed significant phase
      coupling between amygdala and medial frontal cortex, while vascular BOLD
      oscillations showed highly significant phase-coupling between amygdala and
      multiple regions in the supply areas of the anterior and medial cerebral
      arteries. This suggests that not only slow neural and vascular BOLD oscillations
      can be dissociated but also that two strategies may exist to optimize regulation
      of anxiety, that is increased functional connectivity between amygdala and medial
      frontal cortex, and increased cerebral blood flow in amygdala and related
      structures.

PMID- 29368816
TI  - Erratum: Synthesis and in vitro evaluation of melatonin entrapped PLA
      nanoparticles: An oxidative stress and T-cell response using golden hamster. (J
      Biomed Mater Res Part A 2015:103A:3034-3044).

PMID- 29368817
TI  - Plant pathogen effector proteins as manipulators of host microbiomes?

PMID- 29368818
TI  - Staff experiences of double-duty caring: at home and at work.
AB  - Many healthcare, social care and voluntary agency employees are carers at work
      and at home, a phenomenon referred to as double-duty caregiving. Using meta
      ethnography, this article provides a synthesis of qualitative research by
      analysing the original words of the interviewees. A linguistic and metaphoric
      overview provides a deeper, richer picture of the experience of double-duty
      caring, revealing the sacrifices associated with being a carer at home while
      employed in a healthcare system, and the paradoxical effects of holding a
      position in both worlds simultaneously.

PMID- 29368819
TI  - Virtual inpatient surgical service.
AB  - An increased number of emergency secondary care surgical admissions has
      intensified the challenge of meeting acute care patients' needs, while not
      interrupting elective admissions. Aneurin Bevan University Health Board is
      striving to work differently, with the introduction of an innovative nurse
      practitioner-led virtual inpatient (VIP) surgical service. VIP is designed to
      manage emergency patients safely, effectively and in a timely manner, enabling
      them to return home while waiting for investigations. This article describes the
      service and outlines the main outcomes, which include increasing the number of
      surgical emergency patients managed as VIPs, shortening VIP stays, providing more
      timely access to investigations and saving money for the health board.

PMID- 29368820
TI  - Simulation using 'live' adult service users and moulage in a variety of settings.
AB  - This article shows how simulation can be modified and adapted to benefit higher
      education institutions (HEIs) in a variety of situations. These situations can
      involve the engagement of service users (SUs) and moulage, or application of make
      up to simulate clinical presentations, to ensure skill enhancement, ultimately to
      support and empower students so they can achieve their potential. This article
      describes a unique collaboration between staff at an HEI and SUs, who have worked
      together in simulation activities. The development of simulation using SUs is at
      the heart of developing nursing student education and recruitment. It has created
      communities of practice working across traditional departmental boundaries to
      provide innovative learning opportunities for students. This collaboration links
      to the political imperative to improve education in the health and social care
      sector, highlights the integration of skills development into theory, focuses on
      person-centred care and demonstrates how the HEI produces a compassionate and
      caring workforce.

PMID- 29368821
TI  - ?

PMID- 29368822
TI  - ?

PMID- 29368823
TI  - Aprepitant: A Novel Medicaton in the Prevention of Postoperative Nausea and
      Vomiting.

PMID- 29368824
TI  - Screening Mammography: Controversy and Recommendations.

PMID- 29368825
TI  - USPSTF Breast Cancer Screening Guidelines.

PMID- 29368826
TI  - Baylisascaris Procyonis Exposure Case Study.
AB  - We report a case of exposure to raccoon feces found to be contaminated with
      baylisascaris procyonis.  The exposure was recognized early enough by the family
      to allow prophylaxis with albendazole.  Because of the potential fatal or
      neurologically catastrophic effects of this disease immediate treatment is
      indicated.  This is started in advance of environmental studies that are done to
      determine if the feces is indeed contaminated.

PMID- 29368828
TI  - [Two novel mutations in gene SPG4 in patients with autosomal dominant spastic
      paraplegia].
AB  - Hereditary spastik paraplegias (HSP) are a group of neurodegenerative disorders
      with primary lesion of the pyramidal tract. The most frequent autosomal dominant
      form of the disease in Europeans is HSP associated with mutations in the spastin
      gene (SPG4). Analysis of the gene SPG4 was carried out in 52 unrelated families
      with HSP from Bashkortostan by SSCP and following sequencing. Previously
      undescribed frameshift mutations c.322del29 (p.Val108SerfsX18) and c.885del10
      (p.Thr295ThrfsX16) were detected in two unrelated families. Clinical studies have
      shown that, in both families, the disease corresponds to an uncomplicated form of
      hereditary spastic paraplegia, a main feature of which is the lower spastic
      paraparesis without any other symptoms.

PMID- 29368827
TI  - Review of Hyperkalemia in End Stage Renal Disease.
AB  - Potassium balance is maintained in the body by balancing the intake with the
      excretion and the transcellular shifts of potassium.  Excretion of potassium is
      mainly renal as the contribution of the colon to the net potassium secretion of
      the colon to the net potassium secretion is trivial in patients with normal renal
      function.  As the majority of potassium excretion is renal, it is not surprising
      to note that patients with end stage renal disease (ESRD) are at an increased
      risk of developing hyperkalemia in ESRD patients has been estimated to be 3-5%. 
      Maintenance of a stable serum potassium level in patients with ESRD is crucial. 
      We will review the various measures for the management and prevention of
      hyperkalemia in ESRD patients such as dietary restrictions, dialysis and drugs
      enhancing extra renal elimination of potassium.

PMID- 29368829
TI  - [Polymorphism of CD209 and TLR3 genes in populations of North Eurasia].
AB  - The DC-SIGN (dendritic cell-specific intercellular adhesion molecule (ICAM)-3
      grabbing non-integrin) and TLR3 (toll-like receptor 3) proteins are key effectors
      of the innate immunity and particularly play an important role in the organism's
      antiviral defense as pattern-recognition receptors. Previously, we demonstrated
      that certain genotypes and alleles of single nucleotide polymorphisms (SNPs)
      rs2287886 (G/A) in the promoter region of the CD209 gene (encoding DC-SIGN) and
      rs3775291 (G/A, Leu412Phe) in the exon 4 of the TLR3 gene are associated with
      human predisposition to tick-borne encephalitis in the Russian population. In the
      present work, the distribution of genotype and allele frequencies for these SNPs
      was studied in seven populations of North Eurasia, including Caucasians (Russians
      and Germans (from Altai region)), Central Asian Mongoloids (Altaians, Khakass,
      Tuvinians, and Shorians), and Arctic Mongoloids (Chukchi). It was found that the
      CD209 gene rs2287886 SNP A/A genotype and A allele, as well as the TLR3 gene
      rs3775291 SNP G/G genotype and G allele (the frequencies of which in our previous
      studies were increased in tick-borne encephalitis patients as compared with the
      population control (Russian citizens of Novosibirsk)), are preserved with a high
      frequency in Central Asian Mongoloids (who for a long time regularly came in
      contact with tick-borne encephalitis virus in places of their habitation). We
      suggested that predisposition to tick-borne encephalitis in Central Asian
      Mongoloid populations can be predetermined by a different set of genes and their
      polymorphisms than in the Russian population.

PMID- 29368831
TI  - [Aggression and empathy as genetic differentiation factors of urban population].
AB  - Permanent residents of Kharkiv (637 men and 856 women at the age of 45-65 years)
      are tested on the level of aggression and empathy. The average aggression level
      (41.7 points) is higher in migrants (born outside Kharkiv) than in indigenous
      people (36.3 points); the average empathy level is lower in migrants (3.2 points)
      than in indigenous people (5.5 points). The average values of the aggression and
      empathy indices are not associated with ethnicity and degree of miscegenation.
      The correlation between spouses (r) by these personal features is within 0.20
      0.31; the marriage conjugation index (K) is 0.13-0.18. Genotyping of the married
      couples for the rs2235186 SNP of X-linked monoaminooxidase (MAO-A) gene detected
      a positive marriage assortativeness: the C * CC and T * TT pairs are developed
      more frequently than during panmixia; the C * TT and T * CC pairs, less
      frequently. The T allele is coupled with increased aggression level and decreased
      empathy level. The phenotypes of heterozygous women indicate the intermediate
      inheritance of these traits.

PMID- 29368830
TI  - Cellular Angiofibroma Presenting as an Inguinal Subcutaneous Mass: a Case Report
      and Review of the Literature.
AB  - Backgfound: Cellular angiofibroma is a rare benign mesenchymal tumor that occurs
      in the inguinal and vulvovaginal region. We report a case of the tumor occurring
      in the right inguinal region of a 64 old male and a review of the current
      literature. Case: A 64 year old male veteran was referred to our general surgery
      service with an incidentally discovered right inguinal mass on a computerized
      tomography scan.  The scan was performed to follow a history of prostate cancer
      that had been treated with brachytherapy.  Magnetic resonance imaging of the
      lesion helped confirm that the mass did not represent a hernia or an undescended
      testicle.  Surgical resection revealed encapsulated, yellowish, pink tissue
      measuring 6.5 x 5 x 3.5 cm.  Microscopically, the sections showed densely fibrous
      to loose and focally fibromyxoid background of oval to spindle-shaped cells with
      a few scattered plasma cells and mast cells.  Based upon the clinical,
      histologic, and immunohistochemical findings, the lesion was classified as a
      cellular angiofibroma. Conclusion: Cellular angiofibroma of the inguinal region
      is a rare benign encapsulated tumor.It should be considered in the differential
      diagnosis of a male with an inguinal mass proven not to be a hernia or
      undescended testicle.

PMID- 29368832
TI  - [Polymorphism C366G of gene GRIN2B and verbal episodic memory: No association
      with schizophrenia].
AB  - The present study searched for associations between gene GRIN2B (glutamate
      receptor, ionotropic, N-methyl-D-aspartate, subunit 2B) and component processes
      of verbal episodic memory in schizophrenic patients. The Rey Auditory Verbal
      Learning Test (RAVLT) as a part of a large neuropsychological battery was
      administered to 302 patients with schizophrenic spectrum disorders (sample PI).
      Also, 285 patients (sample P2) and 243 healthy controls (sample C2) performed the
      "10 words" test that measures short-term memory. The GRIN2B rs7301328 (C366G)
      polymorphism was genotyped for each subject. There were no associations between
      the polymorphism and any measure of the RAVLT either in the whole PI sample or in
      a subsample of patients with a severe cognitive deficit. The GRIN2B influenced
      immediate recall and proactive interference in the "10 words" test in the control
      group: homozygotes CC recalled fewer words and showed a lower effect of proactive
      interference than carriers of other genotypes. The results suggest that the C366G
      polymorphism could influence verbal episodic memory in the general population,
      but this influence is absent in schizophrenic patients.

PMID- 29368833
TI  - [Gene dilp6 regulates octopamine metabolism in Drosophila melanogaster].
AB  - The effect of strong hypomorphic mutation of the insulin-like protein gene
      (dilp6) on metabolism of octopamine (one of the main biogenic amines in insects)
      was studied in Drosophila melanogaster males and females. The activity of
      tyrosine decarboxylase (the key enzyme of octopamine synthesis) and the activity
      of octopamine-dependent N-acetyltransferase (the enzyme of its degradation) were
      measured. It was demonstrated that the activity of both studied enzymes is
      decreased under normal conditions in the dilp6 41  mutants (as we previously
      demonstrated, this is correlated with an increased level of octopamine). It was
      also found that hypomorphic mutation of the dilp6 gene decreases the intensity of
      tyrosine decarboxylase response to heat stress. Thus, it was demonstrated for the
      first time that insulin-like DILP6 protein in drosophila influences the level of
      octopamine (regulating the activity of the enzyme degrading octopamine).

PMID- 29368834
TI  - [Sequencing and analysis of the resistome of Streptomyces fradiae ATCC19609 in
      order to develop a test system for screening of new antimicrobial agents].
AB  - The paper provides the annotation and data on sequencing the antibiotic
      resistance genes in Streptomyces fradiae strain ATCC19609, highly sensitive to
      different antibiotics. Genome analysis revealed four groups of genes that
      determined the resistome of the tested strain. These included classical
      antibiotic resistance genes (nine aminoglycoside phosphotransferase genes, two
      beta-lactamase genes, and the genes of puromycin N-acetyltransferase,
      phosphinothricin N-acetyltransferase, and aminoglycoside acetyltransferase); the
      genes of ATP-dependent ABC transporters, involved in the efflux of antibiotics
      from the cell (MacB-2, BcrA, two-subunit MDR1); the genes of positive and
      negative regulation of transcription (whiB and padR families); and the genes of
      post-translational modification (serine-threonine protein kinases). A comparative
      characteristic of aminoglycoside phosphotransferase genes in S. fradiae
      ATCC19609, S. lividans TK24, and S. albus J1074, the causative agent of
      actinomycosis, is provided. The possibility of using the S. fradiae strain
      ATCC19609 as the test system for selection of the macrolide antibiotic oligomycin
      A derivatives with different levels of activity is demonstrated. Analysis of more
      than 20 semisynthetic oligomycin A derivatives made it possible to divide them
      into three groups according to the level of activity: inactive (>1 nmol/disk), 10
      substances; with medium activity level (0.05-1 nmol/disk), 12 substances; and
      more active (0.01-0.05 nmol/disk), 2 substances. Important for the activity of
      semisynthetic derivatives is the change in the position of the 33rd carbon atom
      in the oligomycin A molecule.

PMID- 29368835
TI  - [Microsatellite analysis of clonality and individual heterozygosity in natural
      populations of aspen Populus tremula L.: Identification of highly heterozygous
      clone].
AB  - Aspen Populus tremula L. (Salicaceae) is the fast-growing tree species of
      environmental and economic value. Aspen is capable of reproduction by both seeds
      and vegetative means, forming root sprouts. In an adult stand, identification of
      ramets of one clone among the trees of seed origin based on their morphology is
      difficult. A panel of 14 microsatellite loci developed for individual
      identification of aspen was applied for the clonal structure analysis in four
      natural aspen stands of the European part of Russia: Moscow and Voronezh oblasts,
      the Mari-El Republic, and the Republic of Tatarstan. In 52 trees from the Moscow
      sample, 41 multilocus genotypes were identified; in the Voronezh sample, among 30
      individuals, 25 different genotypes were detected; and in the sample from Mari
      El, 32 trees were represented by 13 genotypes. In the stand from Sabinsky
      Forestry, Tatarstan, all of the examined 29 trees were represented by a single
      genotype. The ancestral tree carrier of this genotype which was the most
      heterozygous (0.929) among all studied aspen individuals (sample mean, 0.598)
      obviously has spread over a large territory during several cutting and
      reproduction cycles, currently occupying the area of 2.2 ha. For aspen, usually
      suffering from Aspen trunk rot, such high viability is evidence of resistance to
      the main pathogens. The revealed superclone deserves further study with
      karyological methods and flow cytometry to determine ploidy level and analysis of
      the growth rate and the quality of wood for possible use in plantation forest
      production.

PMID- 29368836
TI  - [Analysis on the ambulatory usage of antibiotics at general hospitals in Asturias
      (2006-2015)].
AB  - OBJECTIVE: The Organization for Economic Co-operation and Development (OECD)
      emphasize, in its report on health policies from 2017 that, Spain is one of the
      countries with largest consumption of antibiotics, 21.6 DHD (defined daily dose
      per 1000 inhibitants per day) in 2014 greater than the average 20.5 DHD in their
      countries, ranking according to the European Center for Disease Prevention and
      Control (ECDC) in the 11th place out of 30 European countries in 2016. The
      outpatient prescription of specialized care is analyzed less frequently, due to
      the greater contribution in consumption and expenditure of primary care. METHODS:
      A descriptive, observational, and retrospective study of the consumption and
      expenditure of the J01 group derived from outpatient prescription (outpatient and
      urgent care) of public hospitals in Asturias, in a period of ten years (2006
      2015). Consumption data were obtained using the database of prescription billing
      of the Health Service of the Principality of Asturias, demographic data were
      provided by the National Institute of Statistics. Consumption was expressed in
      DHD and antibiotics expenditure in: expenditure per capita and expenditure in
      euros per defined daily dose. RESULTS: The average global ambulatory consumption
      for the period was 23.4 DHD, corresponding 11.5% (2.7 DHD) to the ambulatory
      specialty care prescription. In terms of expenditure, it accounted for 13.6% of
      overall outpatient spending on antibiotics. CONCLUSIONS: Outlay and consumption
      had opposite tendencies, the expenditure control measures did not have or had
      little impact on consumption, therefore, independent and spe-cific
      rationalization measures are required in this area.

PMID- 29368837
TI  - Redox-Responsive Amphipathic Dextran Nanomicelles for Solid Tumor Therapy.
AB  - A disulfide bond containing deoxycholic acid-grafted dextran (Dex-SSDCA) was
      successfully prepared for drug delivery. The Dex-SSDCA polymers can self-assemble
      into nanomicelles at concentrations below 56 g/mL and encapsulate doxorubicin
      (DOX) effectively. When exposed to 10 mM Dithiothreitol (DTT), the nanomicelles
      disassembled rapidly and released DOX immediately. The DOX-loaded Dex-SSDCA
      nanomicelles were able to reverse the drug resistance of MCF-7/Adr cells and
      inhibit their growth in vitro. Moreover, DOX-loaded Dex-SSDCA nanomicelles could
      significantly suppress the growth of subcutaneous SKOV-3 ovarian cancer in vivo,
      exerting stronger efficiency on inhibiting tumor angiogenesis and proliferation
      while aggravating apoptosis of tumor cells, in comparison with the negative
      control and free DOX. The in vivo toxicity evaluation demonstrated that the Dex
      SSDCA micelles reduced DOX-induced side effects. This redoxresponsive amphipathic
      dextran is able to enhance the antitumor efficiency and reduce the toxicity of
      doxorubicin, thus has a potential as a drug carrier for cancer therapy.

PMID- 29368838
TI  - [Fundamentally low reproducibility in molecular genetic cancer research].
AB  - The review discusses the causes of multiple failures in cancer treatment, which
      might primarily result from the excessive variability of cancer genomes. They are
      capable of changing their spatial and temporal architecture during tumor
      development. The key reasons of irreproducibility of biomedical data and the
      presumable means for improvement of therapeutic results aiming at targeting the
      most stable tumor traits are suggested.

PMID- 29368839
TI  - [Genetic mechanisms of adaptive immunity emergence in vertebrates].
AB  - The adaptive immune system in vertebrates emerged in a multistep process that can
      be reconstructed on the basis of the data concerning the structure of immune
      systems of modern cartilaginous and bony fishes, as well as of cyclostomes. The
      most probable evolutionary scenario is likely to be as follows: the T cell
      receptor loci emerged on the basis of NK cell-like receptor genes; the antibody
      loci evolved on the basis of T cell receptor loci; the MHC locus arose on the
      basis of the locus responsible for innate immunity of early chordates. The
      ancestral MHC molecules likely participated in the transplantation immunity
      before they acquired the ability of antigen peptide presentation.

PMID- 29368840
TI  - [Prospects for application of breakthrough technologies in breeding: The
      CRISPR/Cas9 system for plant genome editing].
AB  - Integration of the methods of contemporary genetics and biotechnology into the
      breeding process is assessed, and the potential role and efficacy of genome
      editing as a novel approach is discussed. Use of molecular (DNA) markers for
      breeding was proposed more than 30 years ago. Nowadays, they are widely used as
      an accessory tool in order to select plants by mono- and olygogenic traits.
      Presently, the genomic approaches are actively introduced into the breeding
      processes owing to automatization of DNA polymorphism analyses and development of
      comparatively cheap methods of DNA sequencing. These approaches provide effective
      selection by complex quantitative traits, and are based on the full-genome
      genotyping of the breeding material. Moreover, biotechnological tools, such as
      doubled haploids production, which provides fast obtainment of homozygotes, are
      widely used in plant breeding. Use of genomic and biotechnological approaches
      makes the development of varieties less time consuming. It also decreases the
      cultivated areas and financial expenditures required for accomplishment of the
      breeding process. However, the capacities of modern breeding are not limited to
      only these advantages. Experiments carried out on plants about 10 years ago
      provided the first data on genome editing. In the last two years, we have
      observed a sharp increase in the number of publications that report about
      successful experiments aimed at plant genome editing owing to the use of the
      relatively simple and convenient CRISPR/Cas9 system. The goal of some of these
      experiments was to modify agriculturally valuable genes of cultivated plants,
      such as potato, cabbage, tomato, maize, rice, wheat, barley, soybean and sorghum.
      These studies show that it is possible to obtain nontransgenic plants carrying
      stably inherited, specifically determined mutations using the CRISPR/Cas9 system.
      This possibility offers the challenge to obtain varieties with predetermined mono
      and olygogenic traits.

PMID- 29368841
TI  - Multiple erythema migrans due to borreliosis.

PMID- 29368842
TI  - Cicatricial alopecia.
AB  - Cicatricial alopecias (CAs) are clinical pathological conditions that result in
      the complete destruction of hair follicles, which are replaced by fibrotic
      structures. Clinically they are characterized by different inflammatory
      conditions resulting in the end stage in the complete disappearance of hair
      follicle and follicular ostia. CAs are classified in primary cicatricial alopecia
      (PCA) and secondary cicatricial alopecia (SCA). PCA include multiple inflammatory
      diseases with distinctive clinical and histopathologic features that primarily
      affect and destroy the hair follicle. On the other way, diseases classified as
      SCA include inflammatory and neoplastic conditions and physical traumas usually
      primarily affecting the dermis and causing secondary follicular destruction.

PMID- 29368843
TI  - Evidence-based treatment of atopic dermatitis with topical moisturizers.
AB  - Skin barrier restoration represents the mainstay of the treatment of atopic
      dermatitis and the use of moisturizers is recommended by several international
      guidelines. The aim of the study was to investigate through an evidence-based
      medicine analysis the effectiveness and safety of different moisturizing products
      available for a non-pharmacological treatment of atopic dermatitis. A total of 92
      randomized controlled trials (RCTs) have been identified and analyzed. The
      results confirm the presence of a reasonable number of studies highlighting
      moisturizers safety and effectiveness in the treatment of atopic dermatitis by
      improving disease severity, increasing the time of relapse and reducing the time
      of flares. Moisturizers containing urea, glycerin or glycyrrhetinic acid seem to
      show the greater evidence of efficacy being supported by more clinical trials.
      Among the existing moisturizers, those containing a single agent generally work
      although the heterogeneity of RCTs does not allow reaching more definitive
      conclusions. Moisturizers made of a mixture of substances seem to be more
      effective thanks to the presence of different active substances that may exert a
      synergistic effect. A meta-analysis of 4 RCTs confirms the efficacy of a medical
      device containing glycyrrhetinic acid, hyaluronic acid, shea butter, telmesteine,
      and vitis vinifera in the treatment of atopic dermatitis.

PMID- 29368844
TI  - Scleroderma with an update about clinico-pathological correlation.
AB  - Scleroderma is divided into a systemic form called systemic sclerosis and a
      localized form also called morphea. According to 2013 ACR/EULAR Classification
      Criteria for Systemic Sclerosis, developed by the American College of
      Rheumatology (ACR) and the European League Against Rheumatism (EULAR), skin
      thickening of the fingers extending proximal to the metacarpophalangeal joints is
      sufficient for a patient to be classified as having scleroderma. Histological
      examination is not included in the diagnostic criteria and is not routinely
      performed. Skin biopsy is recommended only in the case of diagnostic doubt with
      other scleroderma like disorders (scleromyxedema, scleredema, nephrogenic
      systemic fibrosis). Alternatively, skin biopsy is also often performed for
      research purposes. Indeed, the first step analysis of new cytokines or pathways
      that may contribute to the pathogenesis of the disease requires the evaluation of
      their expression or activation in the skin of scleroderma patients compared to
      healthy controls. The histological picture of the skin in bot localized and
      systemic scleroder shows initially microvascular alterations and chronic
      inflammation while in the more advanced stages skin fibrosis prevails. Localized
      scleroderma (LS) or morphea includes a number of subtypes which are classified
      more according to their clinical presentation rather than histopathological
      pictures. However, some histopathologic changes may be useful in differentiating
      each entity from the others and from other sclerodermoid disorders.

PMID- 29368845
TI  - Cutaneous lupus erythematosus: clinico-pathologic correlation.
AB  - Cutaneous lupus erythematosus (CLE) is a chronic-relapsing disease. It is defined
      as a LE localized to the skin without any significant systemic symptoms. Its
      annual incidence is of 4 cases per 100,000 persons with a prevalence of 73 cases
      per 100,000 persons. The etiology is unknown but it is considered as a prototype
      of autoimmune disease in which genetic factors (HLA), environmental factors
      (photo exposure and cigarette smoking) and pharmacological agents play an
      important role. The most accepted classification includes three clinical
      variants: acute (ACLE), subacute (SCLE) and chronic (CCLE). A fourth variety is
      the intermittent form (ICLE) also called "lupus tumidus" (LET) which is
      considered by some authors a distinct form from CCLE. The skin lesions are
      subdivided into LE specific and LE non-specific. The latter have a considerable
      importance as a symptom of evolution of the disease towards a systemic form of
      lupus (SLE). The histopathology of CLE is characterized by an interface
      dermatitis with vacuolization of the basal layer, a predominantly lymphocytic,
      perivascular and periadnexal infiltrate, epidermal and follicular hyperkeratosis,
      deposit of positive PAS material at the dermo-epidermal junction leading to
      atrophic-cicatricial evolution. Depending on the clinical variants, these
      microscopic features are more or less evident and are associated with
      peculiarities such as deposits of mucin (SCLE and LET), involvement of the
      panniculus in LE panniculitis, disappearance of the adnexa (cicatricial
      alopecia). The relationship between SLE/CLE is still under study: the progression
      of CLE in SLE is reported in a variable percentage of cases ranging from 12 to
      18%. CLE therapy is aimed at preventing recurrences and scarring outcomes.
      Photoprotection with clothing, chemical and physical sunscreens active on UVA and
      UVB radiations is very important. Topical therapy is based on the use of steroids
      and calcineurin inhibitors, while the systemic therapy includes
      hydroxychloroquine as the first drug of choice.

PMID- 29368846
TI  - Cyclosporine in clinical practice: a retrospective study comparing fixed dose and
      body weight-based dose regimens in psoriatic patients.
AB  - BACKGROUND: In the treatment of various diseases, such as diabetes and arterial
      hypertension, fixed dose therapies have been reported to offer a method to
      simplify complex treatment regimens. There are numerous clinical trials proving
      the efficacy of cyclosporine in psoriasis in inducing remission and maintaining
      results, although there are few studies about the treatment optimization of
      cyclosporine. METHODS: We performed a 15-year retrospective observational study
      comparing two groups of psoriatic patients matched for age and sex. We assessed
      the clinical response, the safety and the compliance who took fixed dose of 200
      mg cyclosporine (range 2.2-3.3 mg/kg) compared with a group of patients who took
      body weight-based dosage. Student's t-test was used to assess the difference in
      terms of PASI 75 achievement, patient-reported compliance on a five-point scale,
      DLQI questionnaire, laboratory values and blood pressure. RESULTS: PASI 75
      achievement was not statistically different between the two groups. Compliance
      was good in both groups, and DLQI was also comparable. Laboratory values and
      blood pressure were not significantly different. CONCLUSIONS: Our study showed no
      statistically significant difference between the two groups in PASI reduction and
      PASI 75 achievement, even though the fixed dose was often lower (range 2.2-3.3
      mg/kg) than the dosage administered depending on weight. Fixed dose cyclosporine
      is simple and practical to use in specific clinical settings, in particular when
      the patient's weight ranges from 60 to 90 kg. This approach can result in
      improved clinical outcomes and a better quality of life for psoriatic patients.

PMID- 29368847
TI  - A case of pyoderma gangrenosum, acne, hidradenitis suppurativa (PASH) syndrome
      associated with diabetes mellitus type 1 treated with adalimumab.

PMID- 29368848
TI  - Shagreen-patch in a NF1 patient with a new missense mutation.

PMID- 29368849
TI  - Pyoderma gangrenosum successfully treated with topical tacrolimus.

PMID- 29368850
TI  - Psoriasiform sarcoidosis: an unusual variety.

PMID- 29368851
TI  - A new distal phenotype of Madelung's disease.

PMID- 29368852
TI  - A case of aquagenic wrinkling of the palms.

PMID- 29368853
TI  - When it rains it pours: coexistence of autoimmune bullous disease and plaque
      psoriasis in 8 Caucasian patients.

PMID- 29368854
TI  - Pemphigus herpetiformis resistant to first line therapy: a rare case in
      childhood.

PMID- 29368855
TI  - Gender differences in genital lichen sclerosus.
AB  - BACKGROUND: Studies specifically conducted to assess gender differences in
      genital lichen sclerosus (GLS) are not available. This multicenter study aimed to
      identify possible gender-related differences on GLS clinical features, history
      and course, through collecting data from a large mixed-sex sample of patients.
      METHODS: This was a cross-sectional study on 729 subjects (53.8% females, 46.2%
      males) affected with GLS, consecutively observed within a network of 15 Italian
      dermatology units. The following information was specifically collected: clinical
      features and severity of symptoms related to GLS, extragenital involvement,
      previous therapies, diagnostic suspicion at referral, type of referring
      physicians, development of genital squamous-cell carcinoma (SCC). RESULTS:
      Females complained of symptoms more frequent and severe than men; pallor and
      scarring-sclerosis-atrophy were the most frequent features without gender
      differences; itching- related signs were more frequent in females than in males
      as well as extragenital involvement; prior to receiving a definitive diagnosis,
      females received treatment more frequently than males; 40% of patients were
      referred with a misdiagnosis; the highest rate of correct suspected diagnosis at
      referral came from dermatologists than from other physicians; duration of the
      disease was found to predispose to SCC development. CONCLUSIONS: Our findings
      highlighted several gender differences on clinical presentation and symptom
      profile of GLS. In spite of some characteristic features, misdiagnosis at
      referrals was frequent.

PMID- 29368856
TI  - Dermatomyositis: clinicopathological correlations.
AB  - Dermatomyositis (DM) is a chronic autoimmune disease affecting primarily the
      skeletal muscle and the skin. Although the diagnosis is usually based upon
      clinical and laboratory findings, histopathology is helpful for confirmation
      purposes and is mandatory in amiopathic DM where there is only skin involvement.
      Histologically, the typical cases are characterized by subtle vacuolar interface
      alterations with epidermal atrophy, mild capillary ectasia and sparse
      perivascular lymphocytic infiltrate; these findings are similar to those seen in
      other connective tissue diseases, especially lupus erythematosus. This review
      deals with the specific histological findings that can be found in the different
      presentations of the disease and discuss the most common differential diagnoses.
      As for many other inflammatory skin diseases, the diagnosis of DM is based on a
      strict interaction between the dermatologist and the dermatopathologist.

PMID- 29368857
TI  - Neutrophilic dermatoses: a broad spectrum of disease.
AB  - The neutrophilic dermatoses (NDs) comprise a group of heterogeneous disorders
      characterized by inflammatory skin lesions that histologically show an intense
      inflammatory infiltrate composed primarily by neutrophils, with no evidence of
      infection or vasculitis. Although there are distinct clinical differences in the
      classical lesions of these disorders, many patients have overlapping features. In
      this review, we describe the clinical aspects of the main NDs, including: Sweet
      Syndrome, ND of the dorsal hands, pyoderma gangrenosum, erythema elevatum
      diutinum, subcorneal pustular dermatosis, neutrophilic eccrine hidradenitis,
      rheumatoid neutrophilic dermatitis, neutrophilic panniculitis, and aseptic
      abscesses including their association with underlying diseases and the
      differential diagnoses.

PMID- 29368858
TI  - A case of Axillary Hidradenitis suppurativa treated with topical tacrolimus.

PMID- 29368859
TI  - Incidence of supernumerary nipples in a large population, with relative
      dermoscopic and clinic-pathologic features: an update and a fast approach.

PMID- 29368860
TI  - Reflectance confocal microscopy features of thin versus thick melanomas.
AB  - BACKGROUND: In vivo reflectance confocal microscopy (RCM) plays an increasingly
      important role in differential diagnosis of melanoma. The aim of the study was to
      assess typical confocal features of thin (<=1mm according to Breslow index)
      versus thick (>1mm) melanomas. METHODS: 30 patients with histopathologically
      confirmed cutaneous melanoma were included in the study. Reflectance confocal
      microscopy was performed with Vivascope equipment prior to excision. Fifteen
      melanomas were thin (Breslow thickness <= 1mm) and 15 were thick melanomas
      (Breslow thickness >1mm). RESULTS: In the RCM examination, the following features
      were more frequently observed in thin compared to thick melanomas: edged papillae
      (26.7% vs 0%, p=0.032) and areas with honeycomb or cobblestone pattern (33.3% vs
      6.7%, p=0.068). Both features are present in benign melanocytic lesions, so in
      melanoma are good prognostic factors. The group of thick melanomas compared to
      the group of thin melanomas in the RCM images presented with greater frequency of
      roundish cells (100% vs 40%, p=0.001), non-edged papillae (100% vs 60%, p=0.006),
      numerous pagetoid cells (73.3% vs 33.3%, p=0.028), numerous atypical cells at
      dermal-epidermal junction (53.3% vs 20%, p=0.058) and epidermal disarray (93.3%
      vs 66.7%, p=0.068). CONCLUSIONS: Non-invasive imaging methods helps in deepening
      of knowledge about the evolution and biology of melanoma. The most characteristic
      features for thin melanomas in confocal examination are: fragments of cobblestone
      or honeycomb pattern and edged papillae (as good prognostic factors). The
      features of thick melanomas in RCM examination are: roundish cells, non-edged
      papillae, numerous pagetoid cells at dermal-epidermal junction and epidermal
      disarray.

PMID- 29368861
TI  - A NGFR+ S100- myxoid neurothekeoma: a never described immunohistochemical
      phenotype.

PMID- 29368862
TI  - Clinical and histological evaluation in patients with mycosis fungoides treated
      with UVA1.
AB  - BACKGROUND: UVA1 phototherapy is a valid therapeutic alternative for skin
      lymphoproliferative disorders, although there are few studies concerning its role
      in mycosis fungoides (MF). Our aim was to evaluate and confirm the effectiveness
      of UVA1 phototherapy in patients in early stage Mycosis Fungoides (MF). METHODS:
      We enrolled 12 patients, 9 males and 3 females (mean age 54.83 +/- 9.99, range 36
      74) with a histological diagnosis of mycosis fungoides at early stage. All
      patients were treated with UVA1 for 22 sessions with two different protocols (3
      times or 5 times per week) at the dose of 45 J/cm2. A punch biopsy was performed
      before and after the treatment, to evaluate the variation of histological
      features and of the proliferation index (Ki67/MIB1). RESULTS: At the end of the
      study, we found a marked clinical improvement in all patients, associated to a
      statistically significant reduction of the proliferation index Ki67 / MIB1. Five
      patients achieved a complete clinical and histological response, while six a
      partial one and only one a minimal response. CONCLUSIONS: Although in recent
      years the number of the therapeutic options available for all types of skin
      lymphoproliferative disorders, in particular mycosis fungoides, has increased
      considerably, there are few studies concerning UVA1 phototherapy. Our results
      represent a starting point for further studies, in order to investigate the role
      that these UV-rays can play either alone or in combination with other therapeutic
      regimens.

PMID- 29368863
TI  - Antihypertensive drugs and risk of skin cancer.
AB  - The potential carcinogenic risk of antihypertensive drugs has been examined in
      several studies that reported controversial results. The association between
      treatment with antihypertensives and risk of skin cancer has also been
      questioned, considering the long-term administration of such drugs and the
      ability of some agents to cause photosensitive reactions. In fact, experimental
      and epidemiologic findings suggest a link between drug-induced photosensitivity
      and skin cancer, possibly through the induction of DNA damage in predisposed
      individuals. Antihypertensive medications might influence skin homeostasis
      through additional mechanisms. For instance, some antihypertensive drugs can
      affect epidermal differentiation by interfering with calcium or sodium channels
      in the skin. Mediators in the renin-angiotensin system (RAS) are also involved in
      the modulation of cellular proliferation and angiogenesis. Of note, the existence
      of RAS has been recognized in many organs and tissues, including the skin. The
      available data regarding the relationship between use of different types of
      antihypertensives and skin cancer risk do not allow to draw definite conclusions
      at present. The aim of this article is to summarize the current evidence about
      the association of antihypertensive use with risk of non-melanoma skin cancer,
      melanoma, lip cancer and cutaneous lymphoma. A brief mention of the role of beta
      blockers in melanoma progression has also been added.

PMID- 29368864
TI  - Skin manifestations of rheumatoid arthritis.
AB  - Rheumatoid arthritis is a chronic systemic disease that, in addition to articular
      involvement, may exhibit a variety of extraarticular manifestations. The skin is
      frequently involved mainly in the most severe forms of the disease. Rheumatoid
      nodules, accelerated rheumatoid nodulosis, rheumatoid nodulosis, Felty syndrome,
      rheumatoid vasculitis, pyoderma gangrenosum, rheumatoid neutrophilic dermatosis,
      interstitial granulomatous dermatitis, and palisaded neutrophilic granulomatous
      dermatitis are reviewed both clinically and histologically. Moreover, cutaneous
      reactions related to treatments of rheumatoid arthritis, in particular to
      biologic agents, are described. Early recognition of these entities through a
      clinical and histological correlation permit to optimize the management of
      patients.

PMID- 29368865
TI  - Daylight photodynamic therapy: experience in the treatment of actinic keratosis
      in San Gallicano Institute of Rome and a review of literature.
AB  - BACKGROUND: Actinic keratosis (AK) is a photo-induced skin lesion. It has been
      considered by several authors as in situ squamous cell carcinoma (SCC), that can
      evolve to invasive SCC (iSCC). Given the malignant potential and because it's
      impossible predict which AK will evolve in iSCC, it's necessary to treat each
      lesion. Multiple therapeutic approaches have been described to treat AKs. In
      addition to the topical drugs, photodynamic therapy (PDT) has become an
      established therapeutic modality for grade I and II of AKs of face and scalp.
      Recently the daylight photo-dynamic therapy (DL-PDT) has found extensive use in
      the care of the AK and in the field cancerization. METHODS: 101 patients, 90
      males and 11 females, mean age 71, phototype I-II, with multiple AK I and II of
      the face and the scalp, treated with DL-PDT were retrospectively studied.
      Patients were clinically evaluated for 3 months. RESULTS: The efficacy was
      complete in 16 patients (15,8%), in 71 patients (70,3%) was much improved or
      improved and only in 14 (13,9%) subjects were minimal, while nobody had worsened
      or changed. The majority of patients (84,2%) patients were satisfied of the
      efficacy as well of the cosmetic results, only 15 (14,9%) were low satisfied and
      one patients was no satisfied. CONCLUSIONS: This study confirms that the DL-PDT
      is a good alternative to c-PDT for the treatment of grade I and II AK of the face
      and scalp and in Rome, as in Southern Europe, it's possible to perform the DL-PDT
      in almost every month of year.

PMID- 29368866
TI  - Cutaneous and systemic vasculitides in dermatology: a histological perspective.
AB  - Cutaneous vasculitides encompass a wide and heterogeneous group of diseases
      affecting skin blood vessels that are clinically characterized by polymorphic
      skin lesions, particularly including palpable purpura as well as urticarial and
      necrotic-ulcerative lesions, with possible, albeit rare, extracutaneous
      involvement. Cutaneous leukocytoclastic angiitis and urticarial vasculitis, which
      are the two prototypic and most common variants of this group, are usually
      idiopathic but may also be induced by different triggers, notably drugs and
      infections, or may manifest in association with systemic disorders, particularly
      lupus erythematosus. Vasculitis skin lesions can also occur during the chronic
      relapsing course of systemic vasculitides, such as granulomatosis with
      polyangiitis and eosinophilic granulomatosis with polyangiitis, with which
      cutaneous vasculitides can share clinical and histological features. In order to
      make the diagnosis of a specific form of vasculitis, the cutaneous picture and
      clinical history of the patient have to be correlated with the histological
      pattern, direct immunofluorescence findings, laboratory data and possible
      presence of extracutaneous manifestations. Histology is pivotal for the diagnosis
      of vasculitis and timing of the biopsy is relevant to correctly evaluate the
      characteristics of the inflammatory infiltrate. In this review, we will focus in
      particular on the histological features of cutaneous vasculitides in order to
      differentiate them from the systemic forms and to avoid misdiagnosis when skin
      involvement is the presenting sign of a multisystem vasculitis.

PMID- 29368867
TI  - [Methods of high-throughput plant phenotyping for large-scale breeding and
      genetic experiments].
AB  - Phenomics is a field of science at the junction of biology and informatics which
      solves the problems of rapid, accurate estimation of the plant phenotype; it was
      rapidly developed because of the need to analyze phenotypic characteristics in
      large scale genetic and breeding experiments in plants. It is based on using the
      methods of computer image analysis and integration of biological data. Owing to
      automation, new approaches make it possible to considerably accelerate the
      process of estimating the characteristics of a phenotype, to increase its
      accuracy, and to remove a subjectivism (inherent to humans). The main
      technologies of high-throughput plant phenotyping in both controlled and field
      conditions, their advantages and disadvantages, and also the prospects of their
      use for the efficient solution of problems of plant genetics and breeding are
      presented in the review.

PMID- 29368868
TI  - [Horizontal gene transfer into the genomes of insects].
AB  - Horizontal gene transfer (HGT) is widespread in the world of prokaryotes, but the
      examples of this phenomenon among multicellular animals, particularly insects,
      are few. This review examines the transfer of genetic material to the nuclear
      genomes of insects from the mitochondrial genome (intracellular HGT), as well as
      from the genomes of viruses, bacteria, fungi, and unrelated insects. In most
      cases, the mechanisms of this transfer are unknown. Many pro- and eukaryotic
      genes that moved through the HGT are expressed in the insect genome and in some
      cases can provide the evolutionary innovations that are considered as
      aromorphoses.

PMID- 29368869
TI  - [Chromosome as a chronicler: Genetic dating, historical events, and DNA
      genealogic temptation].
AB  - Nonrecombinant portions of the genome, Y chromosome and mitochondrial DNA, are
      widely used for research on human population gene pools and reconstruction of
      their history. These systems allow the genetic dating of clusters of emerging
      haplotypes. The main method for age estimations is rho statistics, which is an
      average number of mutations from founder haplotype to all modern-day haplotypes.
      A researcher can estimate the age of the cluster by multiplying this number by
      the mutation rate. The second method of estimation, ASD, is used for STR
      haplotypes of the Y chromosome and is based on the squared difference in the
      number of repeats. In addition to the methods of calculation, methods of Bayesian
      modeling assume a new significance. They have greater computational cost and
      complexity, but they allow obtaining an a posteriori distribution of the value of
      interest that is the most consistent with experimental data. The mutation rate
      must be known for both calculation methods and modeling methods. It can be
      determined either during the analysis of lineages or by providing calibration
      points based on populations with known formation time. These two approaches
      resulted in rate estimations for Y-chromosomal STR haplotypes with threefold
      difference. This contradiction was only recently refuted through the use of
      sequence data for the complete Y chromosome; "whole-genomic" rates of single
      nucleotide mutations obtained by both methods are mutually consistent and mark
      the area of application for different rates of STR markers. An issue even more
      crucial than that of the rates is correlation of the reconstructed history of the
      haplogroup (a cluster of haplotypes) and the history of the population. Although
      the need for distinguishing "lineage history" and "population history" arose in
      the earliest days of phylogeographic research, reconstructing the population
      history using genetic dating requires a number of methods and conditions. It is
      known that population history events leave distinct traces in the history of
      haplogroups only under certain demographic conditions. Direct identification of
      national history with the history of its occurring haplogroups is inappropriate
      and is avoided in population genetic studies, although because of its simplicity
      and attractiveness it is a constant temptation for researchers. An example of DNA
      genealogy, an amateur field that went beyond the borders of even citizen science
      and is consistently using the principle of equating haplogroup with lineage and
      population, which leads to absurd results (e.g., Eurasia as an origin of
      humankind), can serve as a warning against a simplified approach for
      interpretation of genetic dating results.

PMID- 29368870
TI  - [Migration as the main factor of the Russia's urban population dynamics].
AB  - This review summarizes the results of the long-term studies performed at the
      Institute of General Genetics, Russian Academy of Sciences, in the field of
      genetic demography of migration processes in Russia and its capital. The main
      population-genetic parameters of migration and their dynamics in Moscow over a
      hundred years are given. Sociodemographic and population-genetic implications of
      migration processes are considered. A model predicting the population gene pool
      dynamics under migration pressure for genes of different localization (autosomal,
      sex-linked, and mitochondrial), exemplified by predicting the allele frequency
      dynamics in the Moscow population of some gene markers, including genes
      accounting for monogenic pathology and genes associated with resistance to
      socially significant diseases, are presented. The paper discusses the selective
      character of migration processes, in particular, processes of emigration, with
      respect to some genetically significant ethnodemographic traits; the problem of
      adaptation of migrants; and adaptive strategies of consolidation of
      ethnoconfessional groups in the megalopolis (compact settlement over the urban
      territory and positive assortative mating with respect to demographic traits). It
      was shown that, owing to the intense influx of migrants and gene flows between
      ethnic groups, the population of the megalopolis is of mixed origin in terms of
      ethnic, anthropologic, and genetic aspects. The results of the study suggest the
      necessity to develop a specific strategy of genetic database formation for the
      population of megalopolises for the purposes of medical genetics and forensic
      medicine.

PMID- 29368871
TI  - [Evolution of genetic diversity and human diseases].
AB  - The problem of development and dispersion of complex diseases in human
      populations requires new views, approaches, hypotheses, and paradigms.
      Evolutionary medicine provides one of the promising approaches to this problem,
      putting the disease into an evolutionary context. Unlike classic approaches
      oriented to proximate issues on structure and mechanisms of a disease,
      evolutionary considerations are broader. It provides the basis for understanding
      the origin, dispersion, and maintenance of the high frequencies of pathological
      phenotypes in modern human populations. In the current paper, we try to review
      the modern concepts on the evolution of human genetic diversity, to shape the
      outlines of evolutionary medicine, and to illustrate evolutionary medical
      problems using our experimental data. Data on genome-wide search for the signals
      of decanalization and adaptation in the human genome and on related biological
      processes and diseases are presented. Some hypotheses and concepts of
      evolutionary medicine may be productive for revealing the mechanisms of origin
      and dispersion of complex diseases and for pathogenetics of multifactorial
      diseases. One of such concepts is the hypothesis of decanalization of genome
      phenome relationships under natural selection during modern human dispersion.
      Probably, the high frequency of alleles associated with complex diseases (and
      partially the high prevalence of diseases themselves) could be explained in the
      framework of the hypothesis.

PMID- 29368872
TI  - [Genetic risk assessment of the joint effect of several genes: Critical
      appraisal].
AB  - When assessing the combined action of genes on the quantitative or qualitative
      phenotype we encounter a phenomenon that could be named the "paradox of the risk
      score summation." It arises when the search of risk allele and assessment of
      their combined action are performed with the same single dataset. Too often such
      methodological error occurs when calculating the so called genetic risk score
      (GRS), which refers to the total number of alleles associated with the disease.
      Examples from numerous published genetic association studies are considered in
      which the claimed statistically significant effects can be attributed to the
      "risk score summation paradox." In the second section of the review we discuss
      the current modifications of multiple regression analysis addressed to the so
      called "n ? p problem" (the number of points is much smaller than the number of
      possible predictors). Various algorithms for the model selection (searching the
      significant predictor combinations) are considered, beginning from the common
      marginal screening of the "top" predictors to LASSO and other modern algorithms
      of compressed sensing.

PMID- 29368873
TI  - Positive surgical margins are predictors of local recurrence in conservative
      kidney surgery for pT1 tumors.
AB  - OBJECTIVES: The clinical significance of positive surgical margin (PSM) after a
      Nephron Sparing Surgery (NSS) is controversial. The aim of this study is to
      evaluate the association between PSM and the risk of disease recurrence in
      patients with pT1 kidney tumors who underwent NSS. MATERIALS AND METHODS:
      Retrospective cohort study. A total of 314 patients submitted to a NSS due to
      stage pT1 renal tumor between January 2010 and June 2015 were included.
      Recurrence-free survival was estimated. The Cox model was used to adjust the
      tumor size, histological grade, pathological stage, age, surgical margins and
      type of approach. RESULTS: Overall PSM was 6.3% (n=22). Recurrence was evidenced
      in 9.1% (n=2) of patients with PSM and 3.5% (n=10) for the group of negative
      surgical margin (NSM). The estimated local recurrence-free survival rate at 3
      years was 96.4% (95% CI 91.9 to 100) for the NSM group and 87.8% (95% CI 71.9 to
      100) for PSM group (p=0.02) with no difference in metastasis-free survival. The
      PSM and pathological high grade (Fuhrman grade III or IV) were independent
      predictors of local recurrence in the multivariate analysis (HR 12.9, 95%CI 1.8
      94, p=0.011 / HR 38.3, 95%CI 3.1-467, p=0.004 respectively). Fuhrman grade proved
      to be predictor of distant recurrence (HR 8.1, 95%CI 1.6-39.7, p=0.011).
      CONCLUSIONS: The PSM in pT1 renal tumors showed to have higher risk of local
      recurrence and thus, worse oncological prognosis.

PMID- 29368874
TI  - Preoperative care of Polypoid exposed mucosal template in bladder exstrophy: the
      role of high-barrier plastic wraps in reducing inflammation and polyp size.
AB  - OBJECTIVE: To assess the role of high-barrier plastic wrap in reducing the number
      and size of polyps, as well as decreasing the inflammation and allergic reactions
      in exstrophy cases, and to compare the results with the application of low
      barrier wrap. MATERIALS AND METHODS: Eight patients with bladder exstrophy
      epispadias complex (BEEC) that had used a low density polyethylene (LDPE) wrap
      for coverage of the exposed polypoid bladder in preoperative care management were
      referred. The main complaint of their parents was increase in size and number of
      polyps. After a period of 2 months using the same wrap and observing the
      increasing pattern in size of polyps, these patients were recommended to use a
      high-barrier wrap which is made of polyvinylidene chloride (PVdC), until closure.
      Patients were monitored for the number and size of polyps before and after the
      change of barriers. The incidence of para-exstrophy skin infection/inflammation
      and skin allergy were assessed. Biopsies were taken from the polyps to identify
      histopathological characteristics of the exposed polyps. RESULTS: The high
      barrier wrap was applied for a mean +/- SD duration of 12+/-2.1 months. Polyps'
      size and number decreased after 12 months. No allergic reaction was detected in
      patients after the usage of PVdC; three patients suffered from low-grade skin
      allergy when LDPE was applied. Also, pre-malignant changes were observed in none
      of the patients in histopathological examination after the application of PVdC.
      CONCLUSION: Polyps' size and number and skin allergy may significantly decrease
      with the use of a high-barrier wrap. Certain PVdC wraps with more integrity and
      less evaporative permeability may be more "exstrophy-friendly".

PMID- 29368875
TI  - Accidental cystectomy during laparoscopic excision of prostatic utricle cyst - a
      rare complication.
AB  - Prostatic utricle cyst is a rare congenital anomaly. Symptomatic cysts require
      treatment. Surgical excision is the treatment of choice, but is challenging due
      to close proximity to vas deferens, ejaculatory ducts, bladder, prostate, rectum
      and pelvic nerves. Complications include rectal injury, ureteral injury,
      impotence, infertility and faecal incontinence. We here report a rare
      complication in which bladder was accidentally removed during laparoscopic
      excision of prostatic utricle cyst. To best of our knowledge such a complication
      has never been reported previously. We also describe the possible cause of this
      accident and suggest ways to prevent this disastrous complication.

PMID- 29368877
TI  - Transperitoneal laparoscopic pyeloplasty in children: does upper urinary tract
      anomalies affect surgical outcomes?
AB  - OBJECTIVE: To assess the feasibility and outcomes of laparoscopic pyeloplasty in
      children with complex ureteropelvic junction obstruction (UPJO) and compare to
      children with iso-lated UPJO without associated urinary tract abnormalities.
      MATERIAL AND METHODS: Medical records of 82 consecutive children submitted to
      transperitoneal laparoscopic pyeloplasty in a 12-year period were reviewed.
      Eleven cases were con-sidered complex, consisting of atypical anatomy including
      horseshoe kidneys in 6 patients, pelvic kidneys in 3 patients, and a duplex
      collecting system in 2 patients. Patients were di-vided into 2 groups: normal
      anatomy (group 1) and complex cases (group 2). Demographics, perioperative data,
      outcomes and complications were recorded and analyzed. RESULTS: Mean age was 8.9
      years (0.5-17.9) for group 1 and 5.9 years (0.5-17.2) for group 2, p=0.08. The
      median operative time was 200 minutes (180-230) for group 1 and 203 minutes (120
      300) for group 2, p=0.15. Major complications (Clavien >=3) were 4 (5.6%) in
      group 1 and 1 (6.3%) in group 2, p=0.52. No deaths or early postoperative
      complications such as: urinoma or urinary leakage or bleeding, occurred. The
      success rate for radiologic improvement and flank pain improvement was comparable
      between the two groups. Re-garding hydronephrosis, significant improvement was
      present in 62 patients (93.4%) of group 1 and 10 cases (90.9%) of group 2,
      p=0.99. The median hospital stay was 4 days (IQR 3-4) for group 1 and 4.8 days
      (IQR 3-6) for group 2, p=0.27. CONCLUSIONS: Transperitoneal laparoscopic
      pyeloplasty is feasible and effective for the management of UPJO associated with
      renal or urinary tract anomalies.

PMID- 29368876
TI  - Clinical and pathologic factors predicting reclassification in active
      surveillance cohorts.
AB  - The incidence of small, lower risk well-differentiated prostate cancer is
      increasing and almost half of the patients with this diagnosis are candidates for
      initial conservative management in an attempt to avoid overtreatment and
      morbidity associated with surgery or radiation. A proportion of patients labeled
      as low risk, candidates for Active Surveillance (AS), harbor aggressive disease
      and would benefit from definitive treatment. The focus of this review is to
      identify clinicopathologic features that may help identify these less optimal AS
      candidates. A systematic Medline/PubMed Review was performed in January 2017
      according to PRISMA guidelines; 83 articles were selected for full text review
      according to their relevance and after applying limits described. For patients
      meeting AS criteria including Gleason Score 6, several factors can assist in
      predicting those patients that are at higher risk for reclassification including
      higher PSA density, bilateral cancer, African American race, small prostate
      volume and low testosterone. Nomograms combining these features improve risk
      stratification. Clinical and pathologic features provide a significant amount of
      information for risk stratification (>70%) for patients considering active
      surveillance. Higher risk patient subgroups can benefit from further evaluation
      or consideration of treatment. Recommendations will continue to evolve as data
      from longer term AS cohorts matures.

PMID- 29368878
TI  - Risk factors for urinary tract infection in children with urinary urgency.
AB  - PURPOSE: To identify which independent variable would be strong predictor of
      febrile urinary tract infection (UTI) in children and adolescents with overactive
      bladder. MATERIALS AND METHODS: A search was made of the institute's database for
      all patients diagnosed with overactive bladder over the preceding four years.
      Children and adolescents under 18 years of age with overactive bladder and no
      neurological or anatomical alterations of the lower urinary tract were included
      in the study. The independent variables were: sex, age, ethnicity (Brazilians of
      African descendence/others), the presence of urinary urgency, daytime
      incontinence, enuresis, frequent urination, infrequent voiding (<=3 voids/day),
      nocturia, holding maneuvers, straining to void, intermittent urinary flow,
      constipation and encopresis. An analysis was conducted to identify patients with
      febrile UTI and subsequently determine predictors of this condition. Univariate
      and multivariate analyses were performed. RESULTS: Overall, 326 patients (214
      girls/112 boys) were evaluated. The mean age of the patients was 7.7+/-3.19 years
      (+/- standard deviation). The incidence of febrile UTI was 39.2%. Being female
      and infrequent voiding were factors significantly associated with febrile UTI,
      both in the univariate and multivariate analyses. CONCLUSIONS: These results show
      that being female and infrequent voiding constituted significant risk factors for
      a diagnosis of febrile UTI in these children.

PMID- 29368879
TI  - 99mTc-DTPA Diuretic Renography with 3 hours late output fraction in the
      evaluation of hydronephrosis in children.
AB  - OBJECTIVE: Dynamic renal scintigraphy complemented by late gravity assisted
      postvoid images to 60 minutes is a frequently used diagnostic test in the
      evaluation of hydronephrosis. The objective of this study is to evaluate the
      effectiveness in acquiring images at 180 minutes to calculate the late output
      fraction (LOF) of 99mTc-DTPA in the diagnosis of ureteropelvic junction
      obstruction (UPJO). MATERIALS AND METHODS: A retrospective study of 177 patients
      (196 renal units) of suspected cases of clinical UPJO was conducted. The patients
      were submitted to at least two dynamic renal scintigraphies of 99mTc-DTPA, with
      the addition of furosemide (F0), with a mean age of 4.3+/-3.8 years for the first
      study, and a follow-up of 2.7+/-2.5 years. RESULTS: For diagnosis based on renal
      curves, a 100% sensitivity, 82.2% specificity, positive predictive value (PPV) of
      10.4% and negative predictive value (NPV) of 100% were estimated. For diagnosis
      based on LOF, a 100% sensitivity, 96.3% specificity, PPV of 35.7% and NPV of 100%
      were estimated. CONCLUSION: A LOF <10% is indicative of UPJO, and a LOF >=15% is
      indicative of no UPJO. The data demonstrate that LOF presents equivalent
      sensitivity and NPV, and higher specificity and PPV in comparison to diagnosis
      based on renal curves, and is useful in the evaluation and follow-up of suspected
      cases of UPJO.

PMID- 29368880
TI  - The influence of exercise on ulcer healing in patients with chronic venous
      insufficiency.
AB  - BACKGROUND: Venous leg ulcer (VLU) affects millions of people, and yet there have
      been no major advances in its treatment for many decades. Is it the time to
      change our approach, and try a multidisciplinary one that could bring about a
      change? The aim of this study is to evaluate whether a regular, home-based
      exercise could be influential in healing the VLU. METHODS: Eighty subjects (mean
      age: 65.13 years) were recruited for 12 weeks. The participants were randomized
      into a control group (N.=20), a compression therapy group (N.=20), an exercise
      group (N.=20) and a compression and exercise group (N.=20). The exercise
      comprised of 10 dorsiflexions each hour while the patient was awake. The first 2
      groups did not perform any exercise while the other two did. Baseline and 3-month
      measurements were performed. These measurements include skin perfusion assessment
      and ulcer size. RESULTS: All patients showed low tcPO2 in the beginning of the
      study. At the point of 3 months of exercise, Laser Doppler flowmetry and ulcer
      size measurements showed significant decrease, P<0.001 in exercise groups,
      however, no real change was demonstrated in the non-exercise groups. Subjects who
      were performing exercise showed significant increase in tcPO2 readings after 3
      months (P<0.001), whereas the tcPO2 readings remained the same in the non
      exercise groups. CONCLUSIONS: We concluded that exercise had a significant effect
      on the VLU healing and this effect may be enhanced further with the help of the
      compression therapy. The tcPO2 and RF measurements may be seen as useful tools in
      evaluating the microvascular changes, and monitoring healing and follow up of the
      venous leg ulcer.

PMID- 29368881
TI  - Targeting Therapy of Neuropilin-1 Receptors Overexpressed Breast Cancer by
      Paclitaxel-Loaded CK3-Conjugated Polymeric Micelles.
AB  - Chemotherapy for breast cancer is significantly restricted by the tumor's physio
      pathological complexity. Here we have constructed a targeted nano-system based on
      PEGylated poly (D, L-lactide) (PEG-PDLLA) using a novel ligand, CLKADKAKC (CK3)
      peptide, for active targeting to Neuropilin-1-rich breast cancer cells. CK3
      increased the cellular uptake of micelles 4.7-fold compared with the free drug
      and nearly 2.2-fold compared with the unmodified micelles (PM), respectively.
      Furthermore, in vivo imaging revealed that CK3-modified micelles (CK3-PM) had
      excellent specific tumor cells targeting and the drug accumulation was also
      enhanced. When paclitaxel (PTX) was loaded into micelles, CK3-PM-PTX induced the
      strongest inhibition and apoptosis against MDA-MB-231 cells in vitro and in vivo.
      These results demonstrated that CK3-modified PEG-PDLLA micelles developed in this
      study could be a potential targeted vehicle for enhancing the chemotherapy of
      breast cancers.

PMID- 29368882
TI  - [Genetic structure of the Russian populations of Pyrenophora tritici-repentis,
      determined by using microsatellite markers].
AB  - The population genetic structure of plant pathogenic fungus Pyrenophora tritici
      repentis was examined using microsatellite (SSR) markers. According to the
      geographical origin of the pathogen populations, they were designated as North
      Caucasian (S, 33 isolates), northwest (Nw, 39), and Omsk (Om, 43). The
      populations were analyzed at the nine most polymorphic SSR loci, at which 75
      alleles were identified. To characterize the genetic variation within and between
      populations, the AMOVA algorithm as implemented in the Arlequin v. 3.5 software
      program was used. The number of alleles per locus ranged from 5 to 12 and their
      sizes varied within the range from 180 to 400 bp. The mean gene diversity at SSR
      loci was high for all populations (H = 0.58-0.75). The populations were
      considerably different in the frequencies of individual alleles of the SSR loci.
      Most isolates in the populations were represented by unique haplotypes. The
      within-population variation of the isolates at molecular markers was 86.4%; among
      the populations, 13.6%. Substantial interpopulation differences were found
      between the Om and S (F st = 0.16) and between the Om and Nw (F st = 0.20)
      populations, whereas between the S and Nw populations, these differences were
      small (F st = 0.05). Thus, it was demonstrated that the population of P. tritici
      repentis from Omsk oblast had the independent status of the geographical
      population; northwest and North Caucasian populations differed in the allelic
      diversity of SSR loci, and despite the low F st value (0.05), they also belonged
      to independent geographical populations.

PMID- 29368883
TI  - [Phylogenetic relationships of the species of Oxytropis DC. subg. Oxytropis and
      Phacoxytropis (Fabaceae) from Asian Russia inferred from the nucleotide sequence
      analysis of the intergenic spacers of the chloroplast genome].
AB  - The nucleotide sequence analysis of trnH-psbA, trnL-trnF, and trnS-trnG
      intergenic spacer regions of chloroplast DNA performed in the representatives of
      the genus Oxytropis from Asian Russia provided clarification of the phylogenetic
      relationships of some species and sections in the subgenera Oxytropis and
      Phacoxytropis and in the genus Oxytropis as a whole. Only the section Mesogaea
      corresponds to the subgenus Phacoxytropis, while the section Janthina of the same
      subgenus groups together with the sections of the subgenus Oxytropis. The
      sections Chrysantha and Ortholoma of the subgenus Oxytropis are not only closely
      related to each other, but together with the section Mesogaea, they are grouped
      into the subgenus Phacoxytropis. It seems likely that the sections Chrysantha and
      Ortholoma should be assigned to the subgenus Phacoxytropis, and the section
      Janthina should be assigned to the subgenus Oxytropis. The molecular differences
      were identified between O. coerulea and O. mandshurica from the section Janthina
      that were indicative of considerable divergence of their chloroplast genomes and
      the species independence of the taxa. The species independence of O. czukotica
      belonging to the section Arctobia was also confirmed.

PMID- 29368884
TI  - Anther culture as an effective tool in winter wheat (Triticum aestivum L.)
      breeding.
AB  - The aim of this study was to determine the effect of genotype and induction
      medium in anther culture of wheat (Triticum aestivum L.). Ten F1 winter wheat
      genotypes were tested in anther culture (AC) to compare the two most frequently
      applied induction media (W14mf and P4mf). Androgenesis was induced during the
      treatment of each tested genotypes and green plants were produced from them using
      both media. Based on statistical analysis, the genotypes significantly influenced
      (at the 0.001 probability level) the efficiency of AC (embryo-like structures
      (ELS), albinos, green plantlets and transplanted plantlets) and the media also
      had a significant effect on the number of ELS and albino plantlets. Both media
      can be used for AC in wheat doubled haploid (DH) plant production. The production
      of ELS and green plantlets was higher in P4mf medium (48.84 ELS/100 anthers, 4.82
      green plantlets/100 anthers) than in W14mf medium (28.14 ELS/100 anthers, 4.59
      green plantlets/100 anthers). However, the green plant regeneration efficiency of
      the microspore-derived structures was 16.9% when using W14mf medium, while this
      value was 9.6% in the case of ELS induced with P4mf medium. The application of
      W14mf medium thus proved to be time- and labour-saving medium in the large-scale
      production of DH wheat plants. In our experiments, 267 DH plants were produced
      for our winter wheat breeding program. The spontaneous rediploidization rate was
      32.72%.

PMID- 29368886
TI  - Superparamagnetic Iron Oxide-Loaded Cationic Polymersomes for Cellular MR Imaging
      of Therapeutic Stem Cells in Stroke.
AB  - MR imaging (MRI) upon cell labeling is an attractive and clinically translatable
      tool for longitudinally monitoring the survival and migration of stem cells. The
      common intracellular delivery of superparamagnetic iron oxide nanoparticles
      (SPIONs) via poly-L-lysine (PLL) requires a high SPION concentration and a long
      incubation period for appropriate cell labeling, which may negatively affect the
      viability and function of stem cells. In this study, we determined the
      performance of a new class of cationic polymersomes in transferring SPIONs into
      green fluorescence protein-modified mesenchymal stem cells (MSCs) for cellular
      MRI in acute ischemic stroke, compared with PLL-coated SPIONs. The results
      demonstrated that the polymersomes had comparable labeling efficiency and
      biological safety as well as a marginal benefit on post-transplantation cell
      survival; the polymersomes had the advantages of a relatively low SPION
      concentration and a substantially shorter labeling period compared with PLL
      coated SPIONs. After transplantation, MSCs labeled using both methods offered a
      similar therapeutic effect on stroke, and cellular MRI could track the in vivo
      distribution and migration behavior of biologically active MSCs; however, MRI
      overestimated the true size of the cell grafts. SPION-loaded cationic
      polymersomes can be used as an alternative for the efficient, rapid, and safe
      labeling of stem cells for cellular MRI.

PMID- 29368887
TI  - [Molecular phylogenetic analysis of the ant genus Formica L. (Hymenoptera:
      Formicidae) from Palearctic region].
AB  - Sixty-five sequences of the mitochondrial DNA cytochrome b gene fragment (759 bp)
      and 23 sequences of the NADH dehydrogenase subunit 6 gene fragment (224 bp) were
      compared in ants of the genus Formica L. from different regions of the Palearctic
      and in Polyergus rufescens Latr. as outgroup. In total, 28 species of the genus
      Formica were examined. As a result, dated trees with a molecular clock were
      constructed showing the phylogenetic relationships of Formica ants. The topology
      of the obtained tree based on the Cyt-b sequences was found to be not consistent
      with the generally accepted opinion on the Formica rufa and F. rufibarbis groups.
      New data on the formation history of the present-day fauna of Formica ants of the
      Palearctic were obtained. It was demonstrated that a considerable fraction of the
      examined species (about a third) were formed in the Quaternary Period.

PMID- 29368888
TI  - [Communication, knowledge and medicine].
AB  - Knowledge developed by humanity has had profound transcendence concerning its
      communication and preservation. An example of this are the advances in
      explanations regarding health and disease, whose mainly printed circulation is
      rapidly losing its place to digital publications. That is the way it happens with
      the Revista Medica del Instituto Mexicano del Seguro Social, whose aim is the
      same: to disseminate new knowledge.

PMID- 29368889
TI  - [Stunting, overweight and obesity during the nutrition transition in
      schoolchildren of Arandas, Jalisco, Mexico].
AB  - BACKGROUND: Nutrition transition provokes changes in the nutritional status of
      individuals subjected to the interaction of various environmental factors;
      therefore, the aim was to demonstrate that nutrition transition is associated
      with socioeconomic changes, eating habits and physical activity, potentially
      involved in stunting, overweight and obesity of schoolchildren. METHODS: Case
      control study. 102 participants from the Instituto Alteno para el Desarrollo de
      Jalisco (cases) and 194 from the elementary school system (controls), aged 5 to
      12 years, were included. Dependent variables were these indexes weight/age (Z),
      height/age (Z), BMI (Z). Independent variables were the socioeconomic and
      demographic characteristics. Student's t test, chi square, odds ratio (OR) and
      95% confidence intervals (95% CI) were estimated. RESULTS: Family income was low
      (p = 0.031) and unstable job was higher in cases: OR = 4.1, 95% CI = 2.8-6.0. The
      frequency of stunting was higher in cases (9.9% vs. 5.9%). The combination of
      overweight/obesity was higher in controls (27.3% vs. 16.8%), OR = 1.85, 95% CI =
      1.0-3.4. CONCLUSIONS: The nutritional status of children of Arandas, Jalisco, has
      been modified by an accelerate nutrition transition, provoked by socioeconomic,
      educational and demographic factors that might have influence on the persistence
      of stunting and an increasing prevalence of overweight/obesity.

PMID- 29368891
TI  - [Characterization of stroke patients attended at IMSS hospitals in Mexico City].
AB  - BACKGROUND: Cerebrovascular disease (CD) is considered a problem of huge social,
      economic and public health implications worldwide in adults and elderly. In
      Mexico, the information concerning the provision of services to people and their
      characteristics is limited. The objective is to describe the characteristics of
      patients with CV who attended the hospitals of the Instituto Mexicano del Seguro
      Social (IMSS) in Mexico City. METHODS: It was carried out a cohort study of
      patients with ischemic or hemorrhagic CD who arrived to IMSS. Patients were
      recruited from seven IMSS general hospitals in Mexico City from June, 2013, to
      October, 2014. RESULTS: We assigned 430 subjects with CD (78.14% had ischemic
      CD). There were no statistical differences regarding gender. The median age of
      patients was 74 years. During their first 72 hours of hospital stay, it was
      assessed language proficiency in 90%, the ability to walk in 16.3% and the
      ability to move extremities in 94%. The main risk factors were hypertension, 84%;
      diabetes mellitus, 46.3%; history of CD, 25.1%; smoking history, 13.7%. 80% of
      patients reported that their health was regular or poor. CONCLUSIONS: General
      characteristics of patients and vascular risk factors are similar to those
      reported by other studies. Secondary prevention strategies are performed in less
      time than that recommended by international standards. It is urgent to design
      strategies to build better ways of care during the acute phase of patients with
      CD.

PMID- 29368890
TI  - [Diagnostic rentability of close pleural biopsy: Tru-cut vs. Cope].
AB  - BACKGROUND: The prevalence of pleural effusion in Mexico is over 400 per 100 000
      inhabitants. The etiology is infectious in 45.7% and neoplastic in 32.6%. Closed
      pleural biopsy sensibility is 48-70% in cancer and 50-59% in tuberculosis using
      Cope or Abrams needle. In 1989, Tru-cut needle biopsy was described in a small
      study for massive pleural effusions with a sensibility of 86%. Our Institute has
      a wide experience with this infrequently procedure with reliable results than
      using Cope needle. Diagnostic yield should be evaluated. We aimed to evaluate the
      diagnostic yield of Tru-cut vs. standard Cope biopsy in the histopathological
      diagnosis of pleural effusion. METHODS: Experimental, not blinded, analytical,
      cross-sectional study. We studied 44 patients (24 male and 20 female) with
      exudative pleural effusion over a period of 14 months. Every patient underwent
      four Tru-cut and four Cope needle biopsies. The diagnostic yield of both methods
      was compared. RESULTS: The mean age of patients was 61.4 +/- 12.2 years. The
      diagnosis was achieved in 25 (57%) of patients using Tru-cut and 22 (50%) of
      patients using Cope's closed pleural biopsy. The diagnostic value was not
      significantly higher (p = 0.41). The most common diagnoses were adenocarcinoma
      (20.5%), mesothelioma (15.9%) and tuberculosis (15.9%). CONCLUSIONS: The
      diagnostic yield of Tru-cut needle biopsy is slightly higher than Cope pleural
      biopsy, very similar to that reported previously. The experience in this
      procedure is an advantage in our clinical practice.

PMID- 29368892
TI  - [Acute myocardial infarction with ST-segment elevation: Code I].
AB  - Code infarction is a timely strategy for the treatment of acute myocardial
      infarction (AMI) with elevation of the ST segment. This strategy has shown an
      increase in survival and quality of life of patients suffering from this event
      around the world. The processes of management and disposition aimed at the
      reduction of time for effective and timely reperfusion are undoubtedly a
      continuous challenge. In the Instituto Mexicano del Seguro Social (IMSS) the
      mortality due to AMI has been reduced more than 50%, which is a historical
      situation that deserves much attention. Nonetheless, the continuous improvement
      and a wider coverage of this strategy in our country are the key factors that
      will outline a change in the natural history of the leading cause of death in
      Mexico. This review focuses on current strategies for the management of patients
      with acute myocardial infarction.

PMID- 29368893
TI  - [Laryngeal disease. Endoscopic characterization of 1493 procedures based on age].
AB  - BACKGROUND: Based on international epidemiology, some laryngeal diseases could be
      more frequent at certain ages. The objective was to describe endoscopic findings
      in patients through distinct decades of age in a laryngoscopy facility. METHODS:
      retrospective and descriptive study; clinical and endoscopic records were
      collected from 1493 procedures performed between 2009 and 2015, and organized in
      five groups of age for analysis. Differences among them were analyzed by chi
      squared and ANOVA. RESULTS: 70% of patients reported dysphonia as a main symptom;
      24% of subjects were referred with cancer diagnosis and just 7% of them, showed
      findings related to malignancy; on the other hand, cancer suspicion increased in
      direct proportion with age (p < 0.0001); inespecific inflammation and other
      benign endoscopic manifestations (e.g. vocal fold paralysis, subglotic stenosis
      and nodules) represented 80% of the whole findings; 14% of the procedures were
      reported as normal. Glottic and supraglottic structures were the two regions
      affected by malignancy; this finding was directly related to advanced age,
      particularly in patients of 70 years of age or older. Finally, subglottic
      stenosis was observed in patients younger than 50 years of age (p < 0.0001).
      CONCLUSIONS: Causes of laryngeal diseases are different in individuals according
      to their age. Carcinoma was more prevalent in adults of 70 years of age or older.
      Benign causes were secondary to inflammatory and functional conditions.

PMID- 29368895
TI  - [Clinical impact factor: can it be measured?]

PMID- 29368894
TI  - [Airway metaplasia related to smoking and environmental pollution through
      sputum].
AB  - BACKGROUND: Both environmental pollution and smoking affect the respiratory
      epithelium, causing cellular adaptation changes. Therefore, this work explores
      the presence of metaplasia in smokers compared with non-smokers from Mexico City.
      METHODS: A prospective cohort study was performed. The sample was performed
      through a home interview covering the five Mexico City zones delimited to the
      study and monitoring of air quality. We searched metaplastic cells and
      inflammation in sputum cytology stained with Papanicolaou technique, and we
      assessed the air quality in Mexico City. We calculated relative risk (RR) and
      attributable risk (AR) in relation to the presence of metaplasia and smoking.
      RESULTS: We performed 1897 home interviews obtaining a final sample of 30
      participants. There were no significant differences between smokers and non
      smokers with the presence of metaplastic cells (p = 0.269), although the
      association of metaplastic cells and inflammation showed a significant difference
      in the non-smokers group (p = 0.010). The RR in association with the presence of
      metaplasia in sputum cytology and smoking was 1.6, and the RA was 0.2.
      CONCLUSIONS: The air quality in this city has led the population to undergo
      changes of cellular adaptation in the respiratory epithelium by the simple fact
      of being exposed to environmental pollution. Metaplastic changes in non-smokers
      suggest strongly that pollution causes the same effect as smoking.

PMID- 29368896
TI  - [Costs and sick leave due to chikungunya in the Instituto Mexicano del Seguro
      Social in Guerrero, Mexico].
AB  - BACKGROUND: Chikungunya fever (CHIK) generally causes temporary sick leave,
      affecting groups of productive age, which represents a significant economic
      impact from the labor point of view. The objective was to estimate costs of
      disability due to chikungunya in the Instituto Mexicano del Seguro Social (IMSS)
      in Guerrero, Mexico. METHODS: Cost assessment of working population from IMSS in
      Guerrero who met the definition of case for CHIK and took sick leave, which was
      registered in the Original Disability Certificates (OCI, according to its
      initials in Spanish) processed from January to April, 2015. Paid sick days were
      multiplied by the current minimum wage of the municipality of Acapulco
      (geographical area A, general = $ 70.10: seventy pesos with 10 cents per day]).
      RESULTS: Of all the OCIs, 31.5% (38 271/12 062) met the criteria for CHIK with a
      total of 41 197 prescribed days and 14 941 paid sick days with an estimated cost
      of 2 397 393.40 pesos (two million, three hundred and ninety seven thousand,
      three hundred and ninety three dollars and forty cents). CONCLUSIONS: Sick leaves
      increase the costs in health systems. These costs increase as increases the
      number of days granted. The average number of days granted is consistent with the
      information published in different articles.

PMID- 29368898
TI  - [Comment to the article "Hemodynamic regime of asymptomatic heart disease
      patients studied by echocardiogram"].

PMID- 29368897
TI  - [Adverse cutaneous reactions to drugs].
AB  - Adverse cutaneous reactions to drugs are any undesirable change in the structure
      or function of the skin. These are among the adverse side effects to common
      drugs. The most commonly implicated drugs are antibiotics and anticonvulsants.
      Cutaneous clinical manifestations are diverse ranging from mild or moderate
      reactions, such as urticaria and maculopapular rash, to severe cutaneous adverse
      reactions (SCAR), which are known due to their high morbidity and mortality
      (among these: Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and
      drug reaction with eosinophilia and systemic symptoms (DRESS). The clinical
      pattern, etiology, prognosis and treatment differ among these skin reactions,
      which is why it is necessary a clear diagnosis based on a comprehensive clinical
      examination, skin biopsy, and specific laboratory tests. The therapeutic options
      depend on the clinical diagnosis. For all reactions, a symptomatic and adequate
      supportive therapy is necessary; in some cases, a systemic immunomodulatory
      therapy can be useful.

PMID- 29368899
TI  - [Obesity hypoventilation syndrome and pulmonary hypertension. An association
      little-known in Mexico].
AB  - The obesity hypoventilation syndrome (OHS) refers to the combination of obesity,
      daytime hypercapnia and sleep-disordered breathing. Obesity has risen to epidemic
      proportions in the last three decades in the United States, Mexico and Europe.
      The OHS is associated with obstructive sleep apnea syndrome in 30%. Without
      treatment, mortality is 46% at 50 months. So in this paper we analyze the OHS,
      obesity and pulmonary hypertension, the pathophysiology, clinical presentation
      and diagnosis as well as the treatment, which is aimed at the correction of sleep
      disordered breathing and hypoxemia; although there is little experience with the
      use of specific pulmonary vasodilator drugs.

PMID- 29368900
TI  - [Disability leave and sick leave in Spain. 2016 legislative update].
AB  - In Spanish, the concepts of discapacidad (disability leave) and incapacidad (sick
      leave) jointly refer to the impairment of a person due to injuries, diseases or
      deficiencies that limit their activity in a social, personal or occupational
      field. However, this common link does not imply that both concepts are the same.
      Statistical data from INE (Instituto Nacional de Estadistica: Statistic National
      Institute) show that Spain had in 2015 3.85 million persons with a disability
      (59.8% were women). Statistical data from 2015 from INSS (Instituto Nacional de
      Seguridad Social: Social Security National Institute) show high levels in the
      number of processes and in workers affected by temporary sick leave, with social
      costs to the social security system. Both concepts have been updated: about
      disability leave, Law 39/2006 adjusted terminology by avoiding the use of
      concepts with discriminating or pejorative connotation. Regarding sick leave, the
      Ley General de Seguridad Social (General Social Security Law)has been amended and
      came into effect in January, 2016. It is necessary to know and distinguish these
      aspects for a better administrative management, and a more oriented information
      to the affected patient.

PMID- 29368901
TI  - [Unicornuate uterus with cavitary non-communicating rudimentary horn: magnetic
      resonance characterization].
AB  - Mullerian duct or paramesonephric anomalies are a group of congenital
      malformations of the female genital tract that result from the alteration in one
      or more stages of embryonic development. The prevalence has increased, probably
      due to the progress of diagnostic imaging methods and the relevance that it has
      acquired in young women with infertility problems. Magnetic resonance imaging
      (MRI) is currently the method of choice for characterizing the different types of
      Mullerian anomalies, its complications and associated pathology. Unicornuate
      uterus correspond to class II of classification of Mullerian duct anomalies
      developed by the American Society for Reproductive Medicine. According to this,
      four subtypes have been identified, each with different clinical implications. A
      cavitated, non-communicating rudimentary horn in a unicornuate uterus is
      associated with an increased incidence of gynecological problems and obstetric
      complications that sometimes threaten the lives of patients, reason why its
      suspicion, diagnosis and treatment is necessary. We report the case of a patient
      with infertility in which this subtype of congenital malformation was discovered.

PMID- 29368902
TI  - [Action of Calendula officinalis essence on bone preservation after the
      extraction].
AB  - BACKGROUND: Calendula officinalis is a phytodrug used as analgesic, antiseptic
      and wound-healing agent due to its collagenogenic effect, which is why it is a
      convenient and affordable treatment that promotes alveolar bone preservation
      after tooth extraction in vivo. The aim of this study was to use Calendula
      officinalis during and after tooth extraction to determine its ability to
      preserve bone after this procedure. METHODS: We established two groups matched by
      age, gender and position of the third molar. We used with patients on the
      experimental group Calendula officinalis diluted 10% as an irrigant during
      surgical extraction of third molars. We performed the conventional way with the
      control group irrigating with saline solution. Subsequently, both groups
      continued to make mouthwash for a week with the irrigating agent. Every week for
      a month, each patient underwent periapical radiography, out of which we took
      measurements of alveolar ridges and depth of alveolar bone, which were compared.
      CONCLUSIONS: There is statistically significant evidence to state that Calendula
      officinalis favorably affects bone preservation after extraction.

PMID- 29368903
TI  - [Anesthesic management during total organic separation of pygopagus conjoined
      twins].
AB  - BACKGROUND: Conjoined twins are among the most rare and challenging congenital
      malformations. The incidence varies from 1:30 000 to 1:200 000 live births.
      Pygopagus twins account for about 10 to 18% of all conjoined twins. CLINICAL
      CASE: We report the case of male conjoined pygopagus twins. They shared medullary
      canal, anal canal and sacrococcygeal region, without any degree of cross
      circulation. At the moment of the surgery, twin 1 had congenital heart disease
      without medical treatment. Twin 2 presented craniofacial malformations. The total
      organic separation was performed electively, by being driven by two teams of
      anesthesiologists with balanced general anesthesia, intravenous and sequential
      induction intubation. Non-invasive and invasive monitoring was used for both
      twins. During the transanesthetic period, twin 1 presented multiple hypercyanotic
      episodes associated to hypovolemia and hypotension. Twin 2 remained stable.
      During the final separation acute bleeding and hemodynamic instability showed up,
      requiring the use of inotropes, vasopressors and blood components. The twins were
      sent to intensive care where they remained under surveillance for three days.
      They were discharged a month and a half after the surgical event. CONCLUSIONS:
      Each type of siamese has specific characteristics depending on the type of union;
      comprehensive knowledge of the morphology and physiopathology of the twins is
      essential for optimal anesthetic management.

PMID- 29368904
TI  - [Non-Hodgkin lymphoma. Incidental finding in a renal donor, 10 years after the
      evolution in recipient].
AB  - BACKGROUND: The incidence of cancer in transplant recipients is higher than in
      the general population. Cutaneous and lymphoproliferative tumors are the primary
      neoplasms that will develop these patients. Little is known about the
      transmission of cancer in organ and tissue donation; it has been described that
      neoplasms can be transmitted to immunosuppressed patients when donor organs with
      neoplasms are inadvertently transplanted. CASE REPORT: Patient of 29 years of age
      who underwent kidney transplantation 10 years ago. The kidney was donated by his
      father, who was 58 years. An incidental finding in the bench surgery showed a
      tumor of about 1 cm in the donated kidney. The intraoperative histopathological
      study showed no alterations, but two weeks after the surgery it was diagnosed
      follicular non-Hodgkin lymphoma grade II retroperitoneal. Subsequently, the donor
      underwent radiotherapy, since it was documented local growth of lymph. The
      recipient was monitored, given that the complete tumor was removed free of
      neoplasia in all its edges. 10 years after the transplantation, both donor and
      recipient are free of neoplastic disease and the latter has a stable renal
      function. CONCLUSIONS: In the presence of an incidental neoplasm from a renal
      donor, the possibility of donation must be reconsidered in the face of an in situ
      neoplasm. We suggest detailed protocol prior to transplant and a thorough
      exploration in the surgical event in order to detect tumors with intraoperative
      study.

PMID- 29368905
TI  - [The aging of Mexican population].
AB  - No abstract.

PMID- 29368906
TI  - [Molecular genetic analysis of five extant reserves of black honeybee Apis
      melifera melifera in the Urals and the Volga region].
AB  - Local populations of the black honeybee Apis mellifera mellifera from the Urals
      and the Volga region were examined in comparison with local populations of
      southern honeybee subspecies A. m. caucasica and A. m. carpatica from the
      Caucasus and the Carpathians. Genetic analysis was performed on the basis of the
      polymorphism of nine microsatellite loci of nuclear DNA and the mtDNA COI-COII
      locus. On the territory of the Urals and the Volga region, five extant
      populations (reserves) of the black honeybee A. m. mellifera were identified,
      including the Burzyanskaya, Tatyshlinskaya, Yuzhno-Prikamskaya, Visherskaya, and
      Kambarskaya populations. These five populations are the basis of the modern gene
      pool of the black honeybee A. m. mellifera from the Urals and the Volga region.
      The greatest proportion of the remaining indigenous gene pool of A. m. mellifera
      (the core of the gene pool of the population of A. m. mellifera) is distributed
      over the entire territory of Perm krai and the north of the Republic of
      Bashkortostan. For the population of A. m. mellifera from the Urals and the Volga
      region, the genetic standards were calculated, which will be useful for future
      population studies of honeybees.

PMID- 29368907
TI  - Authentication of five Barilius species from Indian waters using DNA barcoding.
AB  - Authentic identification of fish species is essential for conserving them as a
      valuable genetic resource in our environment. DNA barcoding of living beings has
      become an important and ultimate tool for establishing their molecular identity.
      Among cyprinids, Barilius is an important genus having nearly 23 species in
      Indian region whose morphological identification is often difficult due to minute
      differences in their features. Five species collected from Indian waters and
      primarily identified as Opsarius bakeri (syn. Barilius bakeri), B. gatensis, B.
      vagra, B. bendelisis and B. ngawa were authenticated by their DNA barcoding based
      on mitochondrial COI gene sequences. Five individuals of each species were taken
      for barcode preparation by COI gene sequencing which yielded one barcode for B.
      ngawa, two barcodes each for O. bakeri, B. gatensis, B. bendelisis and three
      barcodes for B. vagra. The order of inter and intra-specific variation was
      estimated to know a preliminary status of variation prevailing in these cold
      stream fish species significant for evolution and conservation of these valued
      species of our ichthyofauna. Average variation within genera was found to be
      13.6% with intra-specific variation ranging from 0.0% (B. ngawa) to 0.6% (B.
      gatensis). These distance data are in the same order found by various researchers
      globally using COI barcode sequences in different fish species. Phylogenetic
      relatedness among Barilius species and some other cyprinids validate their status
      of individual species as established by conventional taxonomy.

PMID- 29368908
TI  - 3D Hierarchical, Pyramid-Based Cancer Cell Chip for the Detection of Anticancer
      Drug Effects.
AB  - In this study, we developed a novel three-dimensional (3D) cancer cell chip using
      a three-floor hierarchical 3D pyramid structure (3D pyramid) to simulate 3D tumor
      cell growth in vitro and to detect anticancer drugs. The proposed 3D pyramidbased
      cancer cell chip offered substantial advantages for the agglomerate formation of
      tumor cells, in which cells could be maintained as tumor spheroids for up to 3
      weeks. Soon after HeLa tumor cells adhered to the micropatterned pillar
      sidewalls, they were suspended between the pillars based on scanning electron
      microscopy images. Treatment with the anticancer drug oleanolic acid resulted in
      46.33% and 5.86% apoptotic cells on the 2D plate and 3D pyramid-based cell chip,
      respectively, compared with only 0.06% apoptotic cells in the control. The
      increase in chemoresistance to anticancer drugs in the 3D pyramid-based cell chip
      might be a result of cell confluence and hypoxia due to the spheroid formation of
      tumor cells in the 3D pyramid structure. These results indicated that the
      proposed cell chip could potentially be used for anticancer drug screening or can
      be incorporated into other models aimed at prolonging various cell functions in
      culture.

PMID- 29368909
TI  - Withdrawal statement.
AB  - [This retracts the article .].

PMID- 29368910
TI  - [The heteroplasmy level of some mutations in gene MT-CYB among women with
      asymptomatic atherosclerosis].
AB  - Atherosclerosis is a polygenic socially significant disease whose risk factors
      include coronary heart disease, diabetes, hypertension, and myocardial
      infarction. According to the literature, mutations m.14846G>A (G34S), m.15762G>A
      (G339Q), m.15084G>A (W113Ter), and m.15059G>A (G190Ter) of cytochrome B gene (MT
      CYB) are associated with mitochondrial myopathies, myoglobinuria, and exercise
      intolerance. Preliminary studies carried out by the authors made it possible to
      discover an association of certain mitochondrial genome mutations with
      atherosclerotic lesions of aortic intima in people who died as a result of an
      accident or sudden death. The most interesting seemed to be the data on the
      association of mutations m.14846G>A and m.15059G>A of the cytochrome B gene with
      lipofibrous aortic plaques, because these mutations affect the mitochondrial
      respiratory chain enzyme. Defects in the given chain may be the reason for the
      launch of pathogenic mechanisms in the human body. Owing to the fact that
      mutations in the mitochondrial genome are inherited by the maternal type, it was
      decided to analyze cytochrome B gene mutations in a sample of female volunteers
      from Moscow oblast. According to the findings, mutations m.14846G>A and
      m.15059G>A are highly significantly associated with atherosclerotic lesions of
      the carotid arteries: m.14846G>A is antiatherogenic and m.15059G>A is
      proatherogenic.

PMID- 29368912
TI  - Renaissance of Sandmeyer-Type Reactions: Conversion of Aromatic C-N Bonds into C
      X Bonds (X = B, Sn, P, or CF3).
AB  - The Sandmeyer reaction represents an important organic transformation that
      converts an arylamine to an aryl halide using Cu(I) halide via a diazonium salt
      intermediate. The reaction was first reported by Sandmeyer in 1884, and a number
      of named reactions closely related to it have been developed and widely applied
      in organic synthesis throughout the 20th century. These include the Pschorr
      reaction for the synthesis of biaryl tricycles, the Gomberg-Bachmann reaction for
      biaryl formations, the Balz-Schiemann reaction for C-F bond formations, and the
      Meerwein reaction for arylation of alpha,beta-unsaturated carbonyl compounds.
      However, all these reactions were discovered before 1940. In 1977, Doyle and co
      workers reported an organic phase diazotization process, and Kikukawa and Matsuda
      used aryldiazonium salts in transition metal-catalyzed cross-coupling reactions.
      However, completely new processes involving diazonium salts have been seldom
      reported since then, although aryldiazonium salts are widely utilized in modern
      organic synthesis. In the past few years, diazonium salt chemistry has been
      revisited and become a fast-growing research topic. Several novel transformations
      based on diazonium salts have been developed and have been practiced in organic
      synthesis. In 2010, we reported a direct conversion of arylamines to pinacol
      boronates through the reaction of in situ generated aryl diazonium salts with
      B2pin2. This new strategy is under metal-free conditions and thus completely
      avoids contamination by transition metals in the boron products. From readily
      available arylamines various functionalized arylboronates, some of which are
      difficult to access by other methods, can be easily obtained with this reaction.
      Mechanistic investigations indicate the reaction likely follows a radical
      mechanism, which is similar to traditional Sandmeyer-type reactions.
      Subsequently, modified reaction conditions for this transformation appeared in
      the literature, which include light-induced reactions, aqueous-phase
      diazotization methods, and reactions with aryltriazenes as the arene diazonium
      salt surrogates. In addition to the borylation, we have also demonstrated the
      corresponding stannylation and phosphorylation of arylamines with similar
      Sandmeyer-type approaches. The stannylation of arylamines was achieved by the
      reaction of in situ generated diazonium salts with a distannane reagent, while
      phosphorylation is the reaction of arylamines with trimethyl phosphite in the
      presence of tert-butyl nitrite (t-BuONO). With the sequential borylation and
      stannylation approaches, the aromatic compounds bearing two amino groups are
      easily converted into trimethylstannyl arylboronates, which can be further used
      in consecutive Stille and Suzuki-Miyaura cross-couplings. Finally, direct
      conversion of the amino group of arylamines to the trifluoromethyl group has been
      developed through aryl diazonium salts almost simultaneously by several groups.
      These reactions represent a novel strategy to achieve trifluoromethylation of
      aromatic compounds. These developments show the revivification of this age-old
      chemistry, and this Account will summarize the Sandmeyer reaction-related
      transformations that have been developed since 2010.

PMID- 29368913
TI  - Synthesis of Mesoporous gamma-Alumina-Supported Co-Based Catalysts and Their
      Catalytic Performance for Chemoselective Reduction of Nitroarenes.
AB  - Mesoporous gamma-alumina (gamma-MA)-supported cobalt oxides (Co3O4) with large
      surface areas and narrow pore size distributions were first prepared through one
      pot hydrolysis of metal nitrates. The obtained Co3O4/gamma-MA materials were
      impregnated with a water-ethanol solution of 1,10-phenanthroline, followed by
      treatment at 700  degrees C in N2 atmosphere, generating Co-NC/gamma-MA catalysts
      containing N-doped graphitic carbon (NC). The Co-NC/gamma-MA catalysts maintained
      the mesoporous structure of gamma-MA, and Co3O4 was reduced to metallic Co
      nanoparticles highly dispersed in the gamma-MA frameworks. Metallic Co species
      had a strong interaction with NC in the matrices, avoiding the surface oxidation
      of Co particles. The Co-NC/gamma-MA catalysts exhibited superior catalytic
      activity and quantitatively reduced a variety of functionalized nitroarenes to
      the corresponding arylamines with hydrazine hydrate in ethanol at near room
      temperature, affording yields of >99%. The recycling test of 2-chloronitrobenzene
      as a model reaction showed no detectable change in catalyst performance after 10
      cycle reactions.

PMID- 29368911
TI  - Decreased Uptake and Enhanced Mitochondrial Protection Underlie Reduced Toxicity
      of Nanoceria in Human Monocyte-Derived Macrophages.
AB  - Cerium dioxide nanoparticles (nanoceria), currently used as catalysts including
      additives to diesel fuel, also present potential as a novel therapeutic agent for
      disorders involving oxidative stress. However, little is known about the effects
      of nanoceria on primary human cells involved in the innate immune response. Here,
      we evaluate nanoceria effects on monocyte derived macrophages (MDMs) from healthy
      human subjects. Peripheral blood monocytes were isolated from healthy human
      volunteers. MDMs were obtained by maturing monocytes over a five-day period. MDMs
      were exposed to well-characterized nanoceria suspensions (0, 5, 10, 20 MUg/mL)
      for 24 or 48 hours. We evaluated particle uptake, ultrastructural changes,
      cytotoxicity, and mitochondrial damage in MDMs through transmission electron
      microscopy (TEM), confocal imaging, flow cytometry, spectrometry, western blots,
      and immunofluorescence techniques. The role that intracellular concentration of
      nanoceria plays in the toxicity of MDMs was evaluated by 3D image analysis and
      compared to monocytes as a nanoceria sensitive cell model. Nanoceria failed to
      induce cytotoxicity in MDMs at the tested doses. Nanoceria-exposed MDMs showed no
      mitochondrial damage and displayed significant accumulation of anti-apoptotic
      proteins (Mcl-1 and Bcl-2) during the maturation process. TEM and confocal
      analyses revealed efficient uptake of nanoceria by MDMs, however 3D image
      analyses revealed lower nanoceria accumulation per unit cell volume in MDMs
      compared to monocytes. Taken together, our results suggest that mitochondrial
      protection and reduced volume-corrected intracellular nanoparticle concentration
      account for the lower sensitivity of human MDMs to nanoceria.

PMID- 29368914
TI  - Structural and Solar Cell Properties of a Ag-Containing Cu2ZnSnS4 Thin Film
      Derived from Spray Pyrolysis.
AB  - A silver (Ag)-incorporated kesterite Cu2ZnSnS4 (CZTS) thin film was fabricated by
      a facile spray pyrolysis method. Crystallographic analyses indicated successful
      incorporation of various amounts of Ag up to a Ag/(Ag + Cu) ratio of ca. 0.1 into
      the crystal lattice of CZTS in a homogeneous manner without formation of other
      impurity compounds. From the results of morphological investigations, Ag
      incorporated films had larger crystal grains than the CZTS film. The sample with
      a relatively low Ag content (Ag/(Ag + Cu) of ca. 0.02) had a compact morphology
      without appreciable voids and pinholes. However, an increase in the Ag content in
      the CZTS film (Ag/(Ag + Cu) ca. 0.10) induced the formation of a large number of
      pinholes. As can be expected from these morphological properties, the best
      sunlight conversion efficiency was obtained by the solar cell based on the film
      with Ag/(Ag + Cu) of ca. 0.02. Electrostructural analyses of the devices
      suggested that the Ag-incorporated film in the device achieved reduction in the
      amounts of unfavorable copper on zinc antisite defects compared to the bare CZTS
      film. Moreover, the use of a Ag-incorporated film improved band alignment at the
      CdS(buffer)-CZTS interface. These alterations should also contribute to
      enhancement of device properties.

PMID- 29368915
TI  - Correction to Mechanism of Shiga Toxin Clustering on Membranes.

PMID- 29368916
TI  - Design and Development of Graphene Oxide Nanoparticle/Chitosan Hybrids Showing pH
      Sensitive Surface Charge-Reversible Ability for Efficient Intracellular
      Doxorubicin Delivery.
AB  - A novel graphene oxide nanoparticle (GON)-based drug delivery system containing
      GONs as carriers of anticancer drugs and chitosan/dimethylmaleic anhydride
      modified chitosan (CS/CS-DMMA) as surface charge-reversible shells is fabricated
      via the classic self-assembly of the deprotonated carboxyl of GONs and the
      protonated amine of the CS backbone by electrostatic interaction, and CS-DMMA
      serves as the outmost layer. In this GON-based drug delivery system, the GON
      cores as desired carriers might adsorb doxorubicin hydrochloride (DOX) via the pi
      pi stacking interaction between the large pi conjugated structures of GO and the
      aromatic structure of DOX. Meanwhile, the chitosan-based polyelectrolyte shells
      served as a smart protection screen to evade the premature release of the as
      loaded DOX in normal extracellular condition, and then, the release of DOX was
      accelerated because of the detachment of chitosan coating at low pH. Furthermore,
      the re-exposure of amino groups after hydrolysis of CS-DMMA endowed the drug
      delivery system with positive surface charge by taking advantage of the pH
      difference between physiological conditions and the tumor microenvironment to
      enhance the cellular uptake. Then, the pH-dependent site-specific drug release
      was realized. The in vitro investigations confirmed that these promising
      GON/CS/CS-DMMA hybrids with the charge-reversible character possessed various
      merits including excellent encapsulation efficiency, high stability under
      physiological conditions, enhanced cellular uptake by HepG2 cells, and tunable
      intracellular chemotherapeutic agent release profiles, proving its capability as
      an intelligent anticancer agent nanocarrier with enhanced therapeutic effects.
      This smart GON/CS/CS-DMMA vehicle with the surface charge-reversible character
      may be used as a significant drug delivery system for cancer treatment.

PMID- 29368917
TI  - Triple Halide Bridges in Chiral MnII2MnIII6NaI2 Cages: Structural and Magnetic
      Characterization.
AB  - A family of decanuclear chiral clusters with a MnII2MnIII6NaI2 core have been
      synthesized from enantiomerically pure Schiff bases. The new systems consist of
      two MnIIMnIII3NaI units linked by rare triple chloro or bromo bridges between the
      divalent Mn cations. Susceptibility measurements point out the weak
      antiferromagnetic interaction mediated by these kinds of bridges and afford the
      first magnetic measurements for the (MU-Br)3 case.

PMID- 29368918
TI  - New Opportunities Created by Single-Particle Cryo-EM: The Mapping of
      Conformational Space.

PMID- 29368919
TI  - Conjugated Polymer-Based Photoelectrochemical Cytosensor with Turn-On Enable
      Signal for Sensitive Cell Detection.
AB  - In this work, a new photoelectrochemical (PEC) cytosensor was constructed by
      using cationic polyfluorene derivative, poly(9,9-bis(6'-(N,N,N,
      trimethylammonium)hexyl)fluorene-co-alt-1,4-phenylene)bromide (PFP) as the
      photoelectric-responsive material for sensitive cell detection. Positive-charged
      PFP with high photoelectric conversion efficiency can generate robust
      photocurrent under light illumination. In the PEC cytosensor, 3
      phosphonopropionic acid was linked to the indium tin oxide electrode, followed by
      modification with antiepithelial-cell-adhesion-molecule (EpCAM) antibody via
      amide condensation reaction. Thus, target SKBR-3 cells with overexpressed EpCAM
      antigen could be captured onto the electrode via the specific antibody-antigen
      interactions. Upon adding cationic PFP, a favorable electrostatic interaction
      between cationic PFP and negatively charged cell membrane led to a turn-on
      detection signal for target SKBR-3 cells. This new cytosensor not only exhibits
      good sensitivity because of the good photoelectric performance of conjugated
      polymers, but also offers decent selectivity to target cells by taking advantage
      of the specific antibody-antigen recognition.

PMID- 29368920
TI  - Piezoelectric-Induced Triboelectric Hybrid Nanogenerators Based on the ZnO
      Nanowire Layer Decorated on the Au/polydimethylsiloxane-Al Structure for Enhanced
      Triboelectric Performance.
AB  - Here, we demonstrate a novel device structure design to enhance the electrical
      conversion output of a triboelectric device through the piezoelectric effect
      called as the piezo-induced triboelectric (PIT) device. By utilizing the
      piezopotential of ZnO nanowires embedded into the polydimethylsiloxane (PDMS)
      layer attached on the top electrode of the conventional triboelectric device
      (Au/PDMS-Al), the PIT device exhibits an output power density of 50 MUW/cm2,
      which is larger than that of the conventional triboelectric device by up to 100
      folds under the external applied force of 8.5 N. We found that the effect of the
      external piezopotential on the top Au electrode of the triboelectric device not
      only enhances the electron transfer from the Al electrode to PDMS but also boosts
      the internal built-in potential of the triboelectric device through an external
      electric field of the piezoelectric layer. Furthermore, 100 light-emitting diodes
      (LEDs) could be lighted up via the PIT device, whereas the conventional device
      could illuminate less than 20 LED bulbs. Thus, our results highlight that the
      enhancement of the triboelectric output can be achieved by using a PIT device
      structure, which enables us to develop hybrid nanogenerators for various self
      power electronics such as wearable and mobile devices.

PMID- 29368921
TI  - Synergistic Effects of an Irreversible DNA Polymerase Inhibitor and DNA Damaging
      Agents on HeLa Cells.

PMID- 29368922
TI  - Photocaged Nanoparticle Sensor for Sensitive MicroRNA Imaging in Living Cancer
      Cells with Temporal Control.
AB  - Sensitive imaging of microRNA in living cells is of great value for disease
      diagnostics and prognostics. While signal amplification-based strategies have
      been developed for imaging low-abundance disease-relevant microRNA molecules,
      precise temporal control over sensor activity in living cells still remains a
      challenge, and limits their applications for sensing microRNA concentration
      dynamics. Herein, we report a class of photocaged nanoparticle sensors for highly
      sensitive imaging of microRNA in living cells with temporal control. The sensor
      features a DNA-templated gold nanoparticle-quantum dot satellite nanostructure
      which is temporarily inactivated by a photocaged DNA mask. Upon UV light
      irradiation, the sensor restores its activity for catalytic sensing of microRNA
      in living cells via entropy-driven two-step toehold-mediated strand displacement
      reactions. We show that the sensor exhibits quick response to UV light, robust
      intracellular stability, and high specificity and sensitivity for the microRNA
      target. On the basis of this strategy, precise control over sensor activity is
      achieved using an external light trigger, where on-demand sensing could be
      potentially performed with spatiotemporal control.

PMID- 29368923
TI  - Correction to "Photochemically Promoted Aza-Diels-Alder-Type Reaction: High
      Catalytic Activity of the Cr(III)/Bipyridine Complex Enhanced by Visible Light
      Irradiation".

PMID- 29368924
TI  - Scoring of Side-Chain Packings: An Analysis of Weight Factors and Molecular
      Dynamics Structures.
AB  - The protein side-chain packing problem (PSCPP) is a central task in computational
      protein design. The problem is usually modeled as a combinatorial optimization
      problem, which consists of searching for a set of rotamers, from a given rotamer
      library, that minimizes a scoring function (SF). The SF is a weighted sum of
      terms, that can be decomposed in physics-based and knowledge-based terms.
      Although there are many methods to obtain approximate solutions for this problem,
      all of them have similar performances and there has not been a significant
      improvement in recent years. Studies on protein structure prediction and protein
      design revealed the limitations of current SFs to achieve further improvements
      for these two problems. In the same line, a recent work reported a similar result
      for the PSCPP. In this work, we ask whether or not this negative result regarding
      further improvements in performance is due to (i) an incorrect weighting of the
      SFs terms or (ii) the constrained conformation resulting from the protein
      crystallization process. To analyze these questions, we (i) model the PSCPP as a
      bi-objective combinatorial optimization problem, optimizing, at the same time,
      the two most important terms of two SFs of state-of-the-art algorithms and (ii)
      performed a preprocessing relaxation of the crystal structure through molecular
      dynamics to simulate the protein in the solvent and evaluated the performance of
      these two state-of-the-art SFs under these conditions. Our results indicate that
      (i) no matter what combination of weight factors we use the current SFs will not
      lead to better performances and (ii) the evaluated SFs will not be able to
      improve performance on relaxed structures. Furthermore, the experiments revealed
      that the SFs and the methods are biased toward crystallized structures.

PMID- 29368925
TI  - Establishment of Molecular Design Strategy To Obtain Activatable Fluorescent
      Probes for Carboxypeptidases.
AB  - Carboxypeptidases (CPs) are a family of hydrolases that cleave one or more amino
      acids from the C-terminal of peptides or proteins. However, methodology to
      monitor the activities of CPs is poorly developed. Here, we present the first
      versatile design strategy to obtain activatable fluorescent probes for CPs by
      utilizing intramolecular spirocyclization of rhodamine to translate the
      "aliphatic carboxamide to aliphatic carboxylate" structural conversion catalyzed
      by CPs into dynamic fluorescence activation. Based on this novel strategy, we
      developed probes for carboxypeptidases A and B. One of these probes was able to
      detect pancreatic juice leakage in mice ex vivo, suggesting that its suitability
      for intraoperative diagnosis of pancreatic fistula. This design strategy should
      be broadly applicable to CPs, as well as other previously untargetable enzymes,
      enabling development of fluorescent probes to study various pathological and
      biological processes.

PMID- 29368926
TI  - Light-Induced H2 Evolution with a Macrocyclic Cobalt Diketo-Pyrphyrin as a Proton
      Reducing Catalyst.
AB  - Cobalt complexes are well-known catalysts for photocatalytic proton reduction in
      water. Macrocyclic tetrapyridyl ligands (pyrphyrins) and their CoII complexes
      emerged in this context as a highly efficient class of H2 evolution catalysts. On
      the basis of this framework, a new macrocyclic CoII complex consisting of two
      keto-bridged bipyridyl units (Co diketo-pyrphyrin) is presented. The complex is
      synthesized along a convenient route, is well soluble in water, and shows high
      activity as a water reduction catalyst (WRC). In an aqueous system containing
      [Ru(bpy)3]Cl2 as a photosensitizer and NaAscO as a sacrificial electron donor,
      turnover numbers (TONs) of 2500 H2/Co were achieved. Catalysis is terminated by a
      limited electron supply and decomposition of the photosensitizer but not of the
      WRC, highlighting the distinct stability of Co diketo-pyrphyrin.

PMID- 29368927
TI  - Molecular Sieving and Current Rectification Properties of Thin Organic Films.
AB  - For the purpose of preparing well-organized functional surfaces, carbon and gold
      substrates were modified using electroreduction of a tetrahedral-shape
      preorganized tetra-aryldiazonium salt, leading to the deposition of ultrathin
      organic films. Characterization of the modified surfaces has been performed using
      cyclic voltammetry, X-ray photoelectron spectroscopy, infrared absorption
      spectroscopy, ellipsometry, atomic force microscopy, and contact angle
      measurements. The specific design of the tetra-aryldiazonium salts leads to an
      intrinsic structuring of the resulting organic films, allowing molecular sieving
      and current rectification properties toward redox probes in solution.

PMID- 29368928
TI  - Cascade One-Pot Method To Synthesize Isoquinolin-1(2H)-ones with alpha-Bromo
      Ketones and Benzamides via Pd-catalyzed C-H Activation.
AB  - A cross-coupling strategy of palladium-catalyzed ortho-C-H bond activation and
      intramolecular addition of N-C annulation to synthesize isoquinolin-1(2H)-ones
      has been developed. A wide range of alpha-bromo ketones with different
      substituents proceeded smoothly in this reaction, and varieties of isoquinolin
      1(2H)-one derivatives were obtained in moderate to good yields.

PMID- 29368929
TI  - Alternative Sm(II) Species-Mediated Cascade Coupling/Cyclization for the
      Synthesis of Oxobicyclo[3.1.0]hexane-1-ols.
AB  - The allylSmBr/HMPA/MsOH system has been found to be an efficient reagent for the
      "ester-alkene" coupling/cyclization cascade of readily available alpha-allyloxy
      esters. Oxobicyclo[3.1.0]hexane-1-ols were thus prepared in good to excellent
      yields and diastereoselectivities. Investigation on the mechanism suggested the
      possible existence of a new Sm(II) species, namely, CH3SO3SmBr, which resulted
      from the reaction between allylSmBr and MsOH and may be the actual SET reagent.

PMID- 29368930
TI  - Directed Self-Assembly of Topological Defects of Liquid Crystals.
AB  - One of the alluring aspects of liquid crystals (LCs) is their readily
      controllable self-assembly behavior, leading to comprehension of complex
      topological structures and practical patterning applications. Here, we report on
      manipulating various kinds of topological defects by adopting an imprinted
      polymer-based soft microchannel that simultaneously imposes adjustable surface
      anchoring, confinement, and uniaxial alignment. Distinctive molecular orientation
      could be achieved by varying the surface anchoring conditions at the sidewall
      polymer and the rubbing directions on the bottom layer. On this pioneering
      platform, a common LC material, 8CB (4'-n-octyl-4-cyano-biphenyl), was placed
      where various topological defect domains were generated in a periodic
      arrangement. The experimental results showed that our platform can change the
      packing behavior and even the shape of topological defects by varying the rubbing
      condition. We believe that this facile tool to modulate surface boundary
      conditions combined with topographic confinement can open a way to use LC
      materials in potential optical and patterning applications.

PMID- 29368931
TI  - Stereocontrolled Synthesis of 19'-Deoxyperidinin.
AB  - The stereocontrolled convergent synthesis of 19'-deoxyperidinin, 2, which might
      be a useful peridinin analog to understand the ICT characteristics, was
      efficiently achieved by sequential Pd-catalyzed cross-coupling reactions using
      bidirectionally extensible conjugated C5 olefin segments. The crucial 5(2H)
      ylidenedihydrofuran function of 2 was successfully constructed by the Au
      catalyzed regio- and stereoselective 5-exo-dig etherification.

PMID- 29368932
TI  - Pd-Catalyzed Three-Component Reaction of Anilines, Ethyl Vinyl Ether, and Nitro
      Paraffin: Assembly of beta-Nitroamines.
AB  - A novel palladium-catalyzed amination and nitration of ethyl vinyl ether for the
      construction of beta-nitroamine derivatives under mild conditions has been
      developed. This transformation provides a new strategy for the installation of
      amino and nitro from aromatic amines and nitro-paraffin into alkenes. Morpholine
      resulted in the aza-Henry reaction, while DABCO led to the unexpected
      rearrangement.

PMID- 29368933
TI  - Palladium(0)-Catalyzed Intermolecular Asymmetric Allylic Dearomatization of
      Polycyclic Indoles.
AB  - An intermolecular Pd-catalyzed allylic dearomatization reaction of polycyclic
      indoles with substituted allylic carbonates was realized in the presence of a
      newly synthesized chiral phosphoramidite ligand. Various polycyclic indoline and
      indolenine derivatives were successfully synthesized in excellent yields (up to
      99%) with excellent enantioselectivity (up to 98% ee). The obtained products
      could undergo versatile transformations, increasing the application potential of
      the method in organic synthesis.

PMID- 29368934
TI  - Superatomic Two-Dimensional Semiconductor.
AB  - Structural complexity is of fundamental interest in materials science because it
      often results in unique physical properties and functions. Founded on this idea,
      the field of solid state chemistry has a long history and continues to be highly
      active, with new compounds discovered daily. By contrast, the area of two
      dimensional (2D) materials is young, but its expansion, although rapid, is
      limited by a severe lack of structural diversity and complexity. Here, we report
      a novel 2D semiconductor with a hierarchical structure composed of covalently
      linked Re6Se8 clusters. The material, a 2D structural analogue of the Chevrel
      phase, is prepared via mechanical exfoliation of the van der Waals solid
      Re6Se8Cl2. Using scanning tunneling spectroscopy, photoluminescence and
      ultraviolet photoelectron spectroscopy, and first-principles calculations, we
      determine the electronic bandgap (1.58 eV), optical bandgap (indirect, 1.48 eV),
      and exciton binding energy (100 meV) of the material. The latter is consistent
      with the partially 2D nature of the exciton. Re6Se8Cl2 is the first member of a
      new family of 2D semiconductors whose structure is built from superatomic
      building blocks instead of simply atoms; such structures will expand the
      conceptual design space for 2D materials research.

PMID- 29368935
TI  - One-Step Synthesis of Ultrasmall and Ultrabright Organosilica Nanodots with 100%
      Photoluminescence Quantum Yield: Long-Term Lysosome Imaging in Living, Fixed, and
      Permeabilized Cells.
AB  - Water-dispersible nanomaterials with superbright photoluminescence (PL) emissions
      and narrow PL bandwidths are urgently desired for various imaging applications.
      Herein, for the first time, we prepared ultrasmall organosilica nanodots (OSiNDs)
      with an average size of ~2.0 nm and ~100% green-emitting PL quantum efficiency
      via a one-step hydrothermal treatment of two commercial reagents (a silane
      molecule and rose bengal). In particular, the structural reorganization and
      halide loss of rose bengal during the hydrothermal treatment contribute to the
      ultrahigh quantum yield and low phototoxicity of OSiNDs. Owing to their low pH
      induced precipitation/aggregation property, the as-prepared OSiNDs can be used as
      excellent lysosomal trackers with many advantages: (1) They have superior
      lysosomal targeting ability with a Pearson's coefficient of 0.98; (2) The
      lysosomal monitoring time of OSiNDs is up to 48 h, which is much longer than
      those of commercial lysosomal trackers (<2 h); (3) They do not disturb the pH
      environment of lysosomes and can be used to visualize lysosomes in living, fixed,
      and permeabilized cells; (4) They exhibit intrinsic lysosomal tracking ability
      without the introduction of lysosome-targeting ligands (such as morpholine) and
      superior photostability; (5) The easy, cost-effective, and scalable synthetic
      method further ensures that these OSiNDs can be readily used as exceptional
      lysosomal trackers. We expect that the ultrasmall OSiNDs with superior
      fluorescence properties and easily modifiable surfaces could be applied as
      fluorescent nanoprobes, light-emitting diode phosphor, and anticounterfeiting
      material, which should be able to promote the preparation and application of
      silicon-containing nanomaterials.

PMID- 29368936
TI  - Transformation of Alkynes into Chiral Alcohols via TfOH-Catalyzed Hydration and
      Ru-Catalyzed Tandem Asymmetric Hydrogenation.
AB  - A novel full atom-economic process for the transformation of alkynes into chiral
      alcohols by TfOH-catalyzed hydration coupled with Ru-catalyzed tandem asymmetric
      hydrogenation in TFE under simple conditions has been developed. A range of
      chiral alcohols was obtained with broad functional group tolerance, good yields,
      and excellent stereoselectivities.

PMID- 29368937
TI  - Acute appendicitis after a colonic endoscopic submucosal resection.
AB  - We present a case of acute appendicitis as a complication after an Endoscopic
      Submucosal Resection of a colonic polyp.

PMID- 29368938
TI  - Severe obscure gastrointestinal bleeding successfully treated with idarucizumab.
AB  - Idarucizumab is a monoclonal antibody that rapidly reverses the anticoagulant
      effect of dabigatran. The experience with this drug in the setting of
      gastrointestinal bleeding is scarce. We present the case of an 84-year-old male
      with known history of non-valvular atrial fibrillation anticoagulated with
      dabigatran who presented to the emergency room with melena. During his stay in
      the emergency department he suddenly worsened with hemodynamic derangement and
      massive melena so idarucizumab was administered. Gastroscopy and colonoscopy were
      performed without identifying a bleeding source. After the administration of
      idarucizumab, the patient did not presented signs of ongoing bleeding.
      Anticoagulation was resumed on the sixth day and no rebleeding or thromboembolic
      events have been recorded after six months of follow-up. This case and the
      limited information available in the literature suggest that idarucizumab can be
      useful and safe in cases of severe gastrointestinal bleeding with recent intake
      of dabigatran.

PMID- 29368939
TI  - Dysphagia lusoria: a little-known cause of dysphagia.
AB  - It is referred the case report of an 82-year-old female was referred for the
      evaluation of progressive esophageal dysphagia of a six month duration, with a
      recent weight loss of 10% of the normal corporal weight over a six month period.
      The patient reported solid food dysphagia that required liquids to facilitate
      food progression and denied food impaction.

PMID- 29368940
TI  - Inverted Meckel's diverticulum in an adult patient diagnosed via capsule
      endoscopy.
AB  - Meckel's diverticulum is present in 2% of the general population and its inverted
      presentation is rare. The most frequent complications are gastrointestinal
      hemorrhage, obstruction, intussusception and perforation. In general, these
      complications occur in the first two decades of life, and mostly before the
      fourth decade. We present a case of inverted MD that started as a digestive
      hemorrhage of obscure origin in a 77-year-old man who was diagnosed by endoscopic
      capsule.

PMID- 29368941
TI  - Regenerative nodular hyperplasia, portal vein thrombosis and primary
      myelofibrosis: an unusual triple association.
AB  - We report a case of a regenerative nodular hyperplasia with a portal vein
      cavernomatosis with a subsequent progression to symptomatic, occlusive thrombosis
      of the superior mesenteric vein. A thorough investigation resulted in a final
      diagnosis of primary myelofibrosis associated with the V617F mutation in the JAK2
      gene.

PMID- 29368942
TI  - Autoimmune hepatitis as a complication of common variable immunodeficiency.
AB  - In common variable immunodeficiency (CVID) there is a deregulation of the immune
      system, which frequently leads to an increased risk of infections, but also to
      autoimmunity phenomena. Autoimmune hepatitis may develop at any time of CVID's
      evolution, but it is difficult to diagnose due to the frequent absence of
      autoantibodies and low levels of IgG. Early diagnosis is important because
      targeted treatment may allow disease improvement. We present a case of autoimmune
      hepatitis in a patient with CVID.

PMID- 29368943
TI  - A rare mass in the duodenal bulb: Brunner's glands cystadenoma.
AB  - A 56-year-old man referred to our department for treatment of a mass in the
      duodenal bulb. Esophagogastroduodenoscopy(EGD) showed a large spherical mass
      extending from the pyloric canal to the anterior wall of the duodenal bulb.The
      patient received endoscopic submucosal dissection uneventfully.Histology
      demonstrated Brunner's glands csytadenoma finally.

PMID- 29368944
TI  - A specific amino acid formula prevents alcoholic liver disease in rodents.
AB  - Chronic alcohol consumption promotes mitochondrial dysfunction, oxidative stress,
      defective protein metabolism, and fat accumulation in hepatocytes (liver
      steatosis). Inadequate amino acid metabolism is worsened by protein malnutrition,
      frequently present in alcohol-consuming patients, with reduced circulating
      branched-chain amino acids (BCAAs). Here we asked whether dietary supplementation
      with a specific amino acid mixture, enriched in BCAAs (BCAAem) and able to
      promote mitochondrial function in muscle of middle-aged rodents, would prevent
      mitochondrial dysfunction and liver steatosis in Wistar rats fed on a Lieber
      DeCarli ethanol (EtOH)-containing liquid diet. Supplementation of BCAAem, unlike
      a mixture based on the amino acid profile of casein, abrogated the EtOH-induced
      fat accumulation, mitochondrial impairment, and oxidative stress in liver. These
      effects of BCAAem were accompanied by normalization of leucine, arginine, and
      tryptophan levels, which were reduced in liver of EtOH-consuming rats. Moreover,
      although the EtOH exposure of HepG2 cells reduced mitochondrial DNA,
      mitochondrial transcription factors, and respiratory chain proteins, the BCAAem
      but not casein-derived amino acid supplementation halted this mitochondrial
      toxicity. Nicotinamide adenine dinucleotide levels and sirtuin 1 (Sirt1)
      expression, as well as endothelial nitric oxide (eNOS) and mammalian/mechanistic
      target of rapamycin (mTOR) signaling pathways, were downregulated in the EtOH
      exposed HepG2 cells. BCAAem reverted these molecular defects and the
      mitochondrial dysfunction, suggesting that the mitochondrial integrity obtained
      with the amino acid supplementation could be mediated through a Sirt1-eNOS-mTOR
      pathway. Thus a dietary activation of the mitochondrial biogenesis and function
      by a specific amino acid supplement protects against the EtOH toxicity and
      preserves the liver integrity in mammals. NEW & NOTEWORTHY Dietary
      supplementation of a specific amino acid formula prevents both fat accumulation
      and mitochondrial dysfunction in hepatocytes of alcohol-consuming rats. These
      effects are accompanied also by increased expression of anti-reactive oxygen
      species genes. The amino acid-protective effects likely reflect activation of
      sirtuin 1-endothelial nitric oxide synthase-mammalian target of rapamycin pathway
      able to regulate the cellular energy balance of hepatocytes exposed to chronic,
      alcoholic damage.

PMID- 29368946
TI  - Socio-economic predictors of depressive symptoms around old age retirement in
      Swedish women and men.
AB  - OBJECTIVES: To estimate trajectories of depression around old age retirement in
      Swedish women and men and examine if socio-economic status predicted the
      trajectories Methods: The analytic sample comprised 907 women and 806 men from
      the Swedish Longitudinal Occupational Survey of Health. B-spline smoothers and
      group-based trajectory modelling were used to identify groups of individuals with
      similar trajectories of depressive symptoms around retirement. Multinomial
      regression analyses were conducted to investigate if socio-economic factors were
      associated with odds of belonging to trajectory groups with higher depression
      scores. RESULTS: Four depressive symptoms trajectories were identified in both
      genders, all showing similar symptom levels across the retirement transition. Low
      levels of depressive symptoms were observed in the three largest groups. In the
      last trajectory group among women (2.5%) depression scores were moderate to
      severe and among men (3.3%) depression scores were persistent moderate. Higher
      educational level and lower subjectively rated social status were associated with
      higher odds of belonging to trajectory groups with higher levels of depressive
      symptoms in both genders. CONCLUSION: Retirement transition was not associated
      with symptoms of depression. Higher educational level and lower subjective social
      status may predict higher depressive symptom levels the years around old age
      retirement.

PMID- 29368945
TI  - Acute high-fat diet upregulates glutamatergic signaling in the dorsal motor
      nucleus of the vagus.
AB  - Obesity is associated with dysregulation of vagal neurocircuits controlling
      gastric functions, including food intake and energy balance. In the short term,
      however, caloric intake is regulated homeostatically although the precise
      mechanisms responsible are unknown. The present study examined the effects of
      acute high-fat diet (HFD) on glutamatergic neurotransmission within central vagal
      neurocircuits and its effects on gastric motility. Sprague-Dawley rats were fed a
      control or HFD diet (14% or 60% kcal from fat, respectively) for 3-5 days. Whole
      cell patch-clamp recordings and brainstem application of antagonists were used to
      assess the effects of acute HFD on glutamatergic transmission to dorsal motor
      nucleus of the vagus (DMV) neurons and subsequent alterations in gastric tone and
      motility. After becoming hyperphagic initially, caloric balance was restored
      after 3 days following HFD exposure. In control rats, the non- N-methyl-d
      aspartate (NMDA) receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX),
      but not the NMDA receptor antagonist, amino-5-phosphonopentanoate (AP5),
      significantly decreased excitatory synaptic currents and action potential firing
      rate in gastric-projecting DMV neurons. In contrast, both AP5 and DNQX decreased
      excitatory synaptic transmission and action potential firing in acute HFD
      neurons. When microinjected into the brainstem, AP5, but not DNQX, decreased
      gastric motility and tone in acute HFD rats only. These results suggest that
      acute HFD upregulates NMDA receptor-mediated currents, increasing DMV neuronal
      excitability and activating the vagal efferent cholinergic pathway, thus
      increasing gastric tone and motility. Although such neuroplasticity may be a
      persistent adaptation to the initial exposure to HFD, it may also be an important
      mechanism in homeostatic regulation of energy balance. NEW & NOTEWORTHY Vagal
      neurocircuits are critical to the regulation of gastric functions, including
      satiation and food intake. Acute high-fat diet upregulates glutamatergic
      signaling within central vagal neurocircuits via activation of N-methyl-d
      aspartate receptors, increasing vagal efferent drive to the stomach. Although it
      is possible that such neuroplasticity is a persistent adaptation to initial
      exposure to the high-fat diet, it may also play a role in the homeostatic control
      of feeding.

PMID- 29368947
TI  - Development of a Multidimensional Attitude Scale for Organ Donation Research: An
      Example from China.
AB  - This research refined the notion of attitude based on the reasoned action
      perspective of organ donation research at both the conceptual and the operational
      levels in the Chinese context. In Study 1, a multidimensional attitude scale was
      developed based on the salient beliefs of the Chinese toward registering to
      become an organ donor, and the scale's reliability, convergent validity, and
      discriminant validity were established. The results of Study 1 indicated that the
      attitudes toward registering to become an organ donor consisted of two
      statistically independent dimensions, namely, positive and negative attitudes. In
      Study 2, the predictive validity of the multidimensional attitude scale was
      confirmed, and the results indicated that negative attitudes, positive attitudes,
      and subjective norms significantly impacted behavioral intention, which, in turn,
      predicted organ donor registration behavior.

PMID- 29368949
TI  - Headache Classification Committee of the International Headache Society (IHS) The
      International Classification of Headache Disorders, 3rd edition.

PMID- 29368948
TI  - Health economic evaluation in idiopathic pulmonary fibrosis in France.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic,
      progressive, fibrosing interstitial pneumonia of unknown cause. To date, there is
      no specific cure for IPF, and only two treatments (pirfenidone and nintedanib)
      have marketing authorizations and recommendations in international and French
      guidelines. OBJECTIVES: A cost-utility analysis (CUA) has been conducted to
      evaluate the efficiency of nintedanib, in comparison to all available
      alternatives, in a French setting using the official methodological guidelines.
      METHODS: A previously developed lifetime Markov model was adapted to the French
      setting by simulating the progression of IPF patients in terms of lung function
      decline, incidence of acute exacerbations, and death. Considering the effect of
      IPF on patients' quality-of-life, a CUA integrating quality adjusted life years
      (QALY) was chosen as the primary outcome measure in the main analysis. One-way,
      probabilistic, and scenario sensitivity analyses were performed to evaluate the
      robustness of the model. RESULTS: Treatment with nintedanib resulted in an
      estimated total cost of ?76,414 (vs ?82,665 for pirfenidone). In comparison with
      all other available options, nintedanib was predicted to provide the most QALY
      gained (3.34 vs 3.29). This analysis suggests that nintedanib has a 59.0% chance
      of being more effective than pirfenidone and s 77.3% chance of being cheaper than
      pirfenidone. Sensitivity analyses showed the results of the CUA to be robust.
      CONCLUSIONS: In conclusion, this CUA has found that nintedanib appears to be a
      more cost-effective therapeutic option than pirfenidone in a French setting, due
      to fewer acute exacerbations and a better tolerability profile.

PMID- 29368950
TI  - High-concentration topical capsaicin in the management of refractory neuropathic
      pain in patients with neurofibromatosis type 1: a case series.
AB  - AIM: The aim of this case series was to report the use of 8% topical capsaicin
      patch (marketed under the trade name Qutenza(r)) a in the management of
      refractory neuropathic pain (NP) in adult patients with type 1 neurofibromatosis
      (NF1). METHODS: Capsaicin has been suggested for NF1 patients suffering from
      refractory peripheral NP despite several years of analgesic treatments. The patch
      was applied for 60 minutes on the painful area, with tolerability control (blood
      pressure, intensity of pain and dermal reaction). The evaluation was done at the
      beginning of treatment and during the 2 months following the first treatment
      (phone calls at weeks 1, 2, 4 and 8). The primary efficacy criterion was the
      response rate: a patient was considered to be responding if he or she reported an
      average relief >=30% at the time of the follow-up calls. The secondary criteria
      were: interference scores (QCD), Patient Global Impression of Change (PGIC) and
      overall treatment satisfaction, self-reported by the patient. RESULTS: Eight
      patients (5 females/3 males, 41.8 +/- 8.2 years of age) received a first
      treatment with capsaicin. Patients had pre-existing pain for 6.6 years (+/-6.0)
      and were currently receiving an average of 6.1 (+/-3.9) different analgesics. The
      response rate was 37.5%. The three responders felt globally improved and
      satisfied, with the improvement in overall condition as interference scores
      decreased. Apart from the expected local reactions, the treatment was not
      accompanied by systemic side effects. CONCLUSIONS: As suggested in this case
      series, capsaicin provided pain relief in certain NF1 patients with resistant NP.
      The response rate is that expected in multi-line refractory NP. A significant
      benefit on the overall condition of some patients was observed. In addition, this
      topical treatment is administered every 3 months without systemic effects. This
      study is limited by the small number of patients, but was intended to describe a
      new and well tolerated alternative treatment.

PMID- 29368951
TI  - A new phenanthrene dimer from Dendrobium palpebrae.
AB  - A new phenanthrene dimer, namely dendropalpebrone (1), was isolated from the
      whole plant of Dendrobium palpebre, along with nine known compounds (2-10). All
      of the isolates were evaluated for their hydroxyl radical scavenging effects
      using a deoxyribose assay. Dendroflorin (10) showed an appreciable activity, and
      therefore was selected for further studied in RAW264.7 cells. Compound 10
      significantly decreased ROS in H2O2-stimulated RAW264.7 cells in a dose-dependent
      manner, and improved activity of SOD, GPx, and CAT enzymes.

PMID- 29368952
TI  - A new limonoid from stem bark of Chisocheton pentandrus (Meliaceae).
AB  - A new limonoid, pentandricine (1), along with three known limonoids, ceramicine B
      (2), 6-de(acetyloxy)-23-oxochisocheton (3), 6-de(acetyloxy)-23-oxo-7-O
      deacetylchisocheton (4), have been isolated from the stembark of Chisocheton
      pentandrus. The chemical structures of the new compound were elucidated on the
      basis of spectroscopic evidence. All of the compounds were tested for their
      cytotoxic effects against MCF-7 breast cancer cells. Compounds 1-4 showed weak
      and no cytotoxicity against MCF-7 breast cancer cells with IC50 values of 369.84,
      150.86, 208.93 and 120.09 MUM, respectively.

PMID- 29368953
TI  - A novel sesquiterpene derivative with a seven-membered B ring from Illigera
      aromatica.
AB  - A novel sesquiterpene derivative with a seven-membered B ring, illigerine (1),
      along with four known compounds, 1-epi-chiliophyllin (2), 3,4-dihydroxyphenethyl
      alcohol (3), coniferyl alcohol (4) and phenylpropionic acid (5), were isolated
      from Illigera aromatica S. Z. Huang et S. L. Mo. Their structures were identified
      by 1D/2D NMR, HRESIMS and electronic circular dichroism spectra and the cytotoxic
      activity and inhibitory effect of NO production in LPS-stimulated RAW264.7 were
      also evaluated. This is the first report of sesquiterpene isolated from the genus
      Illigera.

PMID- 29368954
TI  - The Effect of Cognitive Activity on Sleep Maintenance in a Subsequent Daytime
      Nap.
AB  - BACKGROUND/OBJECTIVE: The aim of this study is to assess the effects of a
      learning task on the characteristics of a subsequent daytime nap. PARTICIPANTS
      AND METHODS: Thirty-eight subjects were administered a control nap (C) and one
      preceded by a cognitive training session (TR). RESULTS: Relative to C, TR naps
      showed significantly increased sleep duration with decreased sleep latency, as
      well as significantly increased sleep efficiency due to reduced awakening
      frequency. Meaningful trends were also found toward an increase of Stage 2 sleep
      proportion and a reduction of Stage 1 sleep, percentage of wake after sleep onset
      (WASO), and frequency of state transitions. CONCLUSIONS: Our results indicate
      that presleep learning favors sleep propensity and maintenance, offering the
      possibility to explore planned cognitive training as a low-cost treatment for
      sleep impairments.

PMID- 29368956
TI  - Chemical constituents and biological activities of Viburnum macrocephalum f.
      keteleeri.
AB  - Three new compounds (1-3) and seven known compounds (4-10) have been isolated
      from the ethanolic extract of Viburnum macrocephalum f. keteleeri using
      bioactivity-guided fractionation and identified as methyl (2-alpha-L
      rhamnopyranosyloxy)acetate (1), methyl (2R-3-alpha-L-rhamnopyranosyloxy)glycerate
      (2), methyl (3R-4-alpha-L-rhamnopyranosyloxy-3-hydroxy)butanoate (3),
      bridelionoside B (4), (6S,7E,9R)-roseoside (5), linarionoside A (6), 3,7,11
      trimethyl-1,6-dodecadien-3,10,11-triol (7), (+)-8-hydroxylinalool (8), beta
      sitosterol (9) and daucosterol (10). The structures of 1-3, including absolute
      configurations, were determined by spectroscopic data (1H and 13C NMR, HSQC, HMBC
      and ORD) and chemical methods. In addition, compounds 1-8 were assayed for their
      insecticidal and antimicrobial activities. Compounds 7 and 8 exhibited moderately
      insecticidal effects against Mythimna separata with LD50 values of 180 and 230
      MUg g-1, respectively. Compounds 2, 3, 7 and 8 showed varying antimicrobial
      activities with IC50 values ranging from 125 to 529 MUM.

PMID- 29368955
TI  - Translating Cognitive Vulnerability Theory Into Improved Adolescent Depression
      Screening: A Receiver Operating Characteristic Approach.
AB  - Traditionally, screening research tests how well a given symptom inventory can
      identify a concurrent depressive episode. Although developmental psychopathology
      could inform screening protocols for a myriad of depression outcomes (e.g.,
      prospective depressive episodes), approaches typically used in research make it
      difficult to translate these findings. Using a translational analytic approach
      and multiwave longitudinal study design, we examined how screening for cognitive
      vulnerabilities (rumination, dysfunctional attitudes, and attributional style)
      may improve our ability to identify concurrent depressive episodes, prospective
      depressive episodes, first lifetime episodes of depression, and recurrent major
      depressive episodes. There were 473 sixth-grade (early adolescents) and ninth
      grade (middle adolescents; AgeM = 13.15, AgeSD = 1.62) students who completed
      baseline self-report cognitive vulnerability and depressive symptom measures. At
      baseline and every 6 months for 3 years, pediatric depression interviews were
      completed by the caregiver and youth. A receiver operating characteristic (ROC)
      approach was utilized to test our aims. Distinct algorithms best forecasted our
      depression outcomes. Rumination and attributional style emerged as unique and
      incrementally valid predictors for prospective episodes after controlling for
      baseline depressive symptoms. Rumination was the only unique predictor for first
      lifetime depressive episodes. For recurrent major depression, rumination in early
      adolescence and attributional style in middle adolescence served as incremental
      predictors beyond baseline depressive symptoms. Proposed cutoffs and diagnostic
      likelihood ratios are offered for algorithms for each depression outcome.
      Assessing cognitive vulnerability represents a feasible method to improve
      depression screening initiatives. Using an ROC-informed approach can help
      prevention initiatives better leverage the considerable gains made within
      developmental psychopathology research.

PMID- 29368958
TI  - The prevalence of hyperkalemia in the United States.
AB  - OBJECTIVE: The retrospective study aimed to estimate prevalence of hyperkalemia
      using a large US commercial claims database. METHODS: Adults with serum potassium
      lab data (2010 to 2014) and >=1 calendar year of data were included from a large
      US commercial claims database. Hyperkalemia was defined as >=2 serum potassium
      measurements >5.0 mEq/L or one hyperkalemia diagnosis code (ICD-9-CM, 276.7) or
      one sodium polystyrene sulfonate fill. Hyperkalemia prevalence was estimated for
      the overall population and subgroups with hyperkalemia-related comorbidities by
      calendar year. Hyperkalemia prevalence was also standardized to the US population
      to estimate the number of US adults with hyperkalemia. RESULTS: The analysis
      included 2,270,635 patients (2010-2014). The annual prevalence of hyperkalemia in
      the overall population was 1.57% in 2014, with higher rates observed in patients
      with chronic kidney disease (CKD), heart failure, diabetes and hypertension.
      Among patients with CKD and/or heart failure, the 2014 annual prevalence was
      6.35%. Among patients with hyperkalemia, 48.43% had CKD and/or heart failure in
      2014. The prevalence of hyperkalemia was higher in patients with more severe CKD,
      as well as older patients and men. Extrapolating those results to the US
      population supports that 1.55% or 3.7 million US adults had hyperkalemia in 2014.
      CONCLUSIONS: An estimated 3.7 million US adults had hyperkalemia in 2014, and
      this prevalence rate has increased since 2010. In patients with CKD and/or heart
      failure, the annual prevalence of hyperkalemia was 6.35% in 2014, and about half
      of all patients with hyperkalemia have either CKD and/or heart failure.

PMID- 29368957
TI  - Sleep, Circadian Rhythms, and Risk Across Health Domains in Adolescents With an
      Evening Circadian Preference.
AB  - Sleep and circadian rhythm changes during adolescence contribute to increased
      risk across emotional, behavioral, cognitive, social, and physical health
      domains. This study examines if sleep and dim light melatonin onset (DLMO) are
      related to greater risk in these 5 health domains. Participants were 163 (93
      female, age = 14.7 years) adolescents with an evening circadian preference from a
      study funded by the Eunice Kennedy Shriver National Institute of Child Health and
      Human Development. Sleep and circadian measures included weekday total sleep time
      (TST), bedtime, and shut-eye time assessed via sleep diary, the Children's
      Morningness-Eveningness Preferences scale, and DLMO. Health domains included self
      reported emotional, cognitive, behavioral, social, and physical health. Later
      DLMO was significantly associated with shorter weekday TST, later weekday
      bedtime, and later weekday shut-eye time, as well as lower risk in the behavioral
      domain. At the trend level, later DLMO was related to fewer physical health
      problems. Earlier DLMO combined with a later bedtime, later shut-eye time, or
      shorter TST predicted greater risk in the cognitive domain. Later DLMO and
      shorter TST or a later bedtime predicted worse physical health. DLMO timing was
      not related to the emotional or social domain. There is evidence that a
      discrepancy between sleep behaviors and the endogenous circadian rhythm may be
      related to risk in the cognitive domain for adolescents with an evening circadian
      preference. Preliminary evidence also indicated that a delayed DLMO and shorter
      TST or a later bedtime may be related to vulnerability to physical health risk.

PMID- 29368959
TI  - The dynamics of success and failure: how post-behaviour evaluations relate to
      subsequent exercise intentions and behaviour.
AB  - OBJECTIVE: Exercise behaviour change involves multiple experiences with success
      and failure. The Model of Action Phases (MAP) offers a dynamic account of how
      success and failure influence both immediate evaluations and future decisions and
      actions. However, predictions from the MAP have not been formally tested. DESIGN:
      A longitudinal daily diary study was used to examine how post-behaviour
      evaluations of exercise success and failure influence subsequent exercise
      intentions and behaviour. Participants (N = 104) set exercise goals, and then
      kept a daily online exercise diary for four weeks. MAIN OUTCOME MEASURES:
      Participants self-reported exercise behaviour, affective response to exercise,
      self-evaluations after success or failure at following through on intentions to
      exercise, and intentions to exercise in the next week. RESULTS: Multilevel
      modelling revealed significant within- and between-participant relationships
      among post-behaviour evaluations, intentions and subsequent behaviour. Findings
      supported MAP-derived predictions about how success and failure at exercise are
      associated with feelings about exercise and the self, and inform subsequent
      exercise intentions and behaviour. CONCLUSION: Positive post-behaviour
      evaluations of success or failure may stabilise positive intentions and aid
      maintenance of exercise behaviour. Implications of these MAP-based findings for
      intervention design are discussed.

PMID- 29368960
TI  - Dementia: beyond disorders of mood.

PMID- 29368961
TI  - Human abuse potential studies of abuse-deterrent opioids: lessons from oral and
      intranasal studies with morphine abuse-deterrent, extended-release, injection
      molded tablets.
AB  - BACKGROUND: The development and use of abuse-deterrent (AD) opioids is part of a
      multifaceted strategy to reduce misuse, abuse, and diversion, while maintaining
      access for patients with severe pain who may benefit from their analgesic
      efficacy. Morphine AD, extended-release (ER), injection-molded tablets (morphine
      ADER-IMT; ARYMO ER; Egalet US Inc., Wayne, PA) is approved by the FDA as an AD
      opioid. As part of the characterization of AD opioids, assessments of their human
      abuse potential (HAP) are required. Evidence from HAP studies can guide
      clinicians on the use of AD opioids in clinical practice. Herein, we describe HAP
      study design, and how specific AD features can impact the conduct of a study and
      interpretation of its results. OBJECTIVES: To review the design features and
      results of the oral and intranasal HAP studies with morphine-ADER-IMT in order to
      improve the understanding of key elements of HAP studies of AD opioids.
      CONCLUSIONS: Results from HAP studies with morphine-ADER-IMT and other AD opioids
      suggest that key study design features include the release profile (immediate
      release vs extended-release) of the positive control, study drug doses, and the
      way the products are manipulated. These elements can directly impact the outcomes
      of the pharmacokinetic and pharmacodynamic (e.g. Maximum Drug Liking, Overall
      Drug Liking, and Take Drug Again) results. When evaluating HAP studies, it is
      important to understand study design features to assist in the interpretation of
      the results and understand the clinical relevance of the data to help guide
      clinical decision-making about the use of AD opioids.

PMID- 29368963
TI  - COMMENTARY ON MEASUREMENTS OF GLYCEMIC CONTROL.

PMID- 29368964
TI  - 15TH ANNUAL WORLD CONGRESS ON INSULIN RESISTANCE, DIABETES & CARDIOVASCULAR
      DISEASE (WCIRDC).

PMID- 29368966
TI  - PREDICTING RECOVERY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AFTER PROLONGED
      GLUCOCORTICOID USE.
AB  - OBJECTIVE: Prolonged exposure to glucocorticoids lead to hypothalamic-pituitary
      adrenal (HPA) axis suppression that recovers after cessation of treatment. We
      aimed to identify the predictive factors for HPA axis recovery after prolonged
      glucocorticoid use. METHODS: Retrospective review of patients who had undergone
      first short Synacthen test (SST) to assess HPA axis recovery after prolonged use
      of glucocorticoids. RESULTS: A total of 61% (20/33) of patients had adequate SST
      response at a median time of 2 years after diagnosis of adrenal insufficiency.
      Those who had adequate response during SST had higher ambulatory early morning
      cortisol ( P<.01), shorter duration of exposure to glucocorticoids ( P = .01),
      and lower final cumulative hydrocortisone replacement dose ( P = .03). Age,
      gender, body mass index, indications for glucocorticoid use, and basal
      adrenocorticotropic hormone levels were not predictive of HPA axis recovery. On
      multivariate analysis, ambulatory early morning cortisol was the only independent
      predictor of adequate SST response (odds ratio, 1.02; 95% confidence interval,
      1.01 to 1.04; P = .02). Using receiver operating characteristic curve analysis,
      ambulatory early morning cortisol of 8.8 MUg/dL predicted a positive SST response
      with a sensitivity of 70% and specificity of 93%. CONCLUSION: Early morning
      ambulatory cortisol could be used to decide on timely SST in order to prevent
      complications from unnecessary replacement with glucocorticoids. ABBREVIATIONS:
      ACTH = adrenocorticotropic hormone; BMI = body mass index; CV = coefficient of
      variation; HPA = hypothalamic-pituitary-adrenal; SST = short Synacthen test.

PMID- 29368965
TI  - CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND
      AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT
      ALGORITHM - 2018 EXECUTIVE SUMMARY.
AB  - ABBREVIATIONS: A1C = hemoglobin A1C; AACE = American Association of Clinical
      Endocrinologists; ACCORD = Action to Control Cardiovascular Risk in Diabetes;
      ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure;
      ACEI = angiotensin-converting enzyme inhibitor; ADVANCE = Action in Diabetes and
      Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; AGI = alpha
      glucosidase inhibitor; apo B = apolipoprotein B; ASCVD = atherosclerotic
      cardiovascular disease; BAS = bile acid sequestrant; BCR-QR = bromocriptine quick
      release; BMI = body mass index; BP = blood pressure; CCB = calcium channel
      blocker; CHD = coronary heart disease; CKD = chronic kidney disease; CVD =
      cardiovascular disease; DASH = Dietary Approaches to Stop Hypertension; DPP4 =
      dipeptidyl peptidase 4; eGFR = estimated glomerular filtration rate; ER =
      extended release; FDA = Food and Drug Administration; GLP1 = glucagon-like
      peptide 1; HDL-C = high-density lipoprotein cholesterol; IMPROVE-IT = Improved
      Reduction of Outcomes: Vytorin Efficacy International Trial; LDL-C = low-density
      lipoprotein cholesterol; LDL-P = low-density lipoprotein particle; Look AHEAD =
      Look Action for Health in Diabetes; NPH = neutral protamine Hagedorn; OSA =
      obstructive sleep apnea; RCT = randomized controlled trial; SU = sulfonylurea;
      SGLT2 = sodium glucose cotransporter-2; SMBG = self-monitoring of blood glucose;
      T2D = type 2 diabetes; TZD = thiazolidinedione; VADT = Veterans Affairs Diabetes
      Trial.

PMID- 29368967
TI  - ENDO ECHO IMPROVES PRIMARY CARE PROVIDER AND COMMUNITY HEALTH WORKER SELF
      EFFICACY IN COMPLEX DIABETES MANAGEMENT IN MEDICALLY UNDERSERVED COMMUNITIES.
AB  - OBJECTIVE: To determine whether participation in a multidisciplinary
      telementorship model of healthcare delivery improves primary care provider (PCP)
      and community health worker (CHW) confidence in managing patients with complex
      diabetes in medically underserved regions. METHODS: We applied a well-established
      healthcare delivery model, Project ECHO (Extension for Community Healthcare
      Outcomes), to the management of complex diabetes (Endo ECHO) in medically
      underserved communities. A multidisciplinary team at Project ECHO connected with
      PCPs and CHWs at 10 health centers across New Mexico for weekly videoconferencing
      virtual clinics. Participating PCPs and CHWs presented de-identified patients and
      received best practice guidance and mentor-ship from Project ECHO specialists and
      network peers. A robust curriculum was developed around clinical practice
      guidelines and presented by weekly didactics over the ECHO network. After 2 years
      of participation in Endo ECHO, PCPs and CHWs completed self-efficacy surveys
      comparing confidence in complex diabetes management to baseline. RESULTS: PCPs
      and CHWs in rural New Mexico reported significant improvement in self-efficacy in
      all measures of complex diabetes management, including PCP ability to serve as a
      local resource for other healthcare providers seeking assistance in diabetes
      care. Overall self-efficacy improved by 130% in CHWs ( P<.0001) and by 60% in
      PCPs ( P<.0001), with an overall large Cohen's effect size. CONCLUSION: Among
      PCPs and CHWS in rural, medically underserved communities, participation in Endo
      ECHO for 2 years significantly improved confidence in complex diabetes
      management. Application of the ECHO model to complex diabetes care may be useful
      in resource-poor communities with limited access to diabetes specialist services.
      ABBREVIATIONS: CHW = community health worker; CME = Continuing Medical Education;
      ECHO = Extension for Community Healthcare Outcomes; FQHC = federally qualified
      health center; PCP = primary care provider.

PMID- 29368968
TI  - A MESSAGE FROM THE EDITOR-IN-CHIEF.

PMID- 29368969
TI  - RESPONSE LETTER.

PMID- 29368970
TI  - RE: DIABETIC KETOACIDOSIS IN PATIENTS WITH TYPE 2 DIABETES ON SGLT-2 INHIBITORS:
      AN ONGOING CONCERN.

PMID- 29368971
TI  - Ligand-dependent transcriptional induction of lethal autophagy: A new perspective
      for cancer treatment.
AB  - Dendrogenin A (DDA) is a mammalian metabolite that displays anticancer and
      chemopreventive properties in mice. At the cancer cell level, DDA induces
      differentiation and death. We investigated herein the nature of DDA cytoxicity in
      cancer cells. We showed that DDA triggers biochemical and cellular features of
      macroautophagy/autophagy and that autophagy is cytotoxic. DDA induces both the
      accumulation of pro-lysosomal sterols and stimulates the expression of regulators
      of autophagy such as NR4A, LC3 and TFEB through binding to the liver X receptor
      (LXR), a ligand-dependent transcription factor consisting of 2 isoforms, NR1H2
      and NR1H3. These effects are not observed with canonical LXR agonists such as the
      oxysterol 22(R)-hydroxycholesterol or the synthetic molecules T0901317 and
      GW3965. DDA effects were measured on melanoma and acute myeloid leukemia cells
      including patient-derived leukemia cells in vitro and in vivo. Importantly the
      induction of lethal autophagy kills cells independently of their cytogenetic
      subgroups and does not differentiate bulk cancer cells from cancer cell
      progenitors. Together these data show that DDA drives LXR to induce the
      expression of autophagic genes leading to cancer cells death. This opens up new
      perspectives for cancer treatment.

PMID- 29368972
TI  - Propensity for movement specific reinvestment by physiotherapists: Implications
      for education.
AB  - Previous studies have shown that the propensity for conscious monitoring and
      control of movement (i.e. movement specific reinvestment) influences the
      acquisition of movement skills. Physiotherapists, whose primary function is to
      promote effective human movement, also develop specialized movement skills that
      are necessary to perform diagnostic and therapeutic procedures. To explore the
      implications for promoting expertise, this current study examined
      physiotherapists' propensity for movement-specific reinvestment. Practitioners
      and students in physiotherapy, and other rehabilitation, and non-health
      professionals, completed the Movement Specific Reinvestment Scale, which measures
      two dimensions of reinvestment: 1) conscious motor processing (CMP); and 2)
      movement self-consciousness (MS-C). Physiotherapists scored significantly higher
      than other professionals on both CMP and MS-C. Specifically among
      physiotherapists, those with relatively fewer years of practice tended to have
      higher MS-C scores. Movement-specific reinvestment appears to be a characteristic
      of physiotherapists that could be relevant for understanding the ways in which
      novices think and act as they progress to expertise. Further research is
      recommended to examine the role of reinvestment in performance of different tasks
      of varying complexity by novice physiotherapists.

PMID- 29368974
TI  - Formulation development and process analysis of drug-loaded filaments
      manufactured via hot-melt extrusion for 3D-printing of medicines.
AB  - Three dimensional(3D)-printing via fused deposition modeling (FDM) allows the
      production of individualized solid dosage forms. However, for bringing this
      benefit to the patient, active pharmaceutical ingredient (API)-loaded filaments
      of pharmaceutical grade excipients are necessary as feedstock and have to be
      produced industrially. As large-scale production of API-loaded filaments has not
      been described in literature, this study presents a development of 3D-printable
      filaments, which can continuously be produced via hot-melt extrusion. Further, a
      combination of testing methods for mechanical resilience of filaments was applied
      to improve the prediction of their printability. Eudragit RL was chosen as a
      sustained release polymer and theophylline (30%) as thermally stable model drug.
      Stearic acid (7%) and polyethylene glycol 4000 (10%), were evaluated as suitable
      plasticizers for producing 3D-printable filaments. The two formulations were
      printed into solid dosage forms and analyzed regarding their dissolution
      profiles. This revealed that stearic acid maintained sustained release properties
      of the matrix whereas polyethylene glycol 4000 did not. Analysis of the
      continuous extrusion process was done using a design of experiments. It showed
      that powder feed rate and speed of the stretching device used after extrusion
      predominantly determine the diameter of the filament and thereby the mechanical
      resilience of a filament.

PMID- 29368973
TI  - Extending conceptual understanding: How interprofessional education influences
      affective domain development.
AB  - Interprofessional learning (IPL) can influence affective domain development of
      students through teaching activities that facilitate learning with, from, and
      about other professions. Current quantitative evidence offers limited explanation
      of how this learning is achieved within IPL programmes. This article tests a
      conceptual framework drawn from theories on IPL and affective domain development
      (attitudes, values, and behaviours) to explain what works for whom, when, and in
      what circumstances. The objectives of the study were twofold: to evaluate the
      impact of the IPL programme on the student's attitudes and values, and to
      identify behaviour changes in clinical practice towards interprofessional
      working. Using an action research approach, based in practice, an IPL programme
      was delivered over 6 weeks. Students from five professions, nursing, radiography,
      physiotherapy, social work, and podiatry (n = 63), participated over the two
      action research cycles and in semi-structured focus groups (n = 37). The recorded
      personal experiences of the IPL activities on the students were examined in
      relation to the type of activity; impact on the affective domain of learning
      (attitude, value, or behaviour) and self-reported outcome on application to their
      practice. Modification in affective domain development was measured to
      identification or internalisation stage for 30 of the students. Self-reported
      outcomes on application to practice included direct impact on patient care,
      personal resilience building, improved communication, and ability to challenge
      practice. This article presents a conceptual framework not evident in current
      research, in regard to what IPL works for whom, in what circumstances, and when.
      IPL activities that address a personal reward or incentive and are delivered over
      four weeks, imitating 'circles of care,' that explore self-assessment, team
      building, and reflection can lead to sustained change in values, attitudes, and
      behaviours.

PMID- 29368975
TI  - Effects of 1800 MHz RF-EMF exposure on DNA damage and cellular functions in
      primary cultured neurogenic cells.
AB  - PURPOSE: To systematically evaluate the effects of 1800 MHz radiofrequency
      electromagnetic fields (RF-EMF) exposure on DNA damage and cellular functions in
      primary cultured neurogenic cells. MATERIALS AND METHODS: The primary cultured
      astrocytes, microglia and cortical neurons were exposed to RF-EMF at a SAR of 4.0
      W/kg. The DNA damage was evaluated by gammaH2AX foci formation assay. The
      secretions of pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) in
      astrocytes and microglia, microglial phagocytic activity and neuronal development
      were examined by enzyme-linked immunosorbent assay, phagocytosis assay and
      immunofluorescent staining on microtubule-associated protein tau, microtubule
      associated protein 2, postsynaptic density 95 and gephyrin, respectively.
      RESULTS: RF-EMF exposure did not significantly induce gammaH2AX foci formation in
      three primary cultured neurogenic cells. Furthermore, RF-EMF exposure did not
      significantly affect the secretion of cytokines in astrocytes and microglia, and
      the morphological indicators of dendrites or synapses of cortical neurons.
      However, the exposure significantly reduced the phagocytic activity of microglia
      and inhibited the axon branch length and branch number of cortical neurons.
      CONCLUSIONS: Our data demonstrated that exposure to RF-EMF did not elicit DNA
      damage but inhibited the phagocytic ability of microglia and the axon branch
      length and branch number of cortical neurons.

PMID- 29368976
TI  - Effects of EphB4 receptor expression on colorectal cancer cells, tumor growth,
      vascularization and composition.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common causes of cancer
      related deaths worldwide. Increased expression of the molecular target, EphB4
      receptor, has been observed in several cancer types. However, studies on the role
      of EphB4 receptor in CRC have yielded contradictory results. The aim of this
      study was to investigate the influence of EphB4 expression levels on CRC cell
      behavior and its contribution to tumor growth and vascularization. METHODS:
      SW480, LIM2405 and CT26 CRC cell lines were transfected with EphB4 expression
      vector. High EphB4 expressing cells were compared to low EphB4 expressing empty
      vector controls. Proliferation and migration assays as well as EphrinB2-Fc cell
      stimulations were conducted in vitro and subcutaneous xenografts of CRC were
      analyzed in vivo. RESULTS: High EphB4 expression enhanced migratory ability of
      these CRC cell lines in vitro and contributed to a significant increase in tumor
      growth and vascularization in vivo. Tumours induced with high EphB4 expressing
      SW480 and LIM2405 cells yielded homogenous masses densely packed with cancer
      cells. EphrinB2-Fc cell stimulations induced cell clustering of high EphB4
      expressing SW480 and LIM2405 in vitro. CONCLUSION: These results suggest that
      with enhanced vascularization and an increase in migratory abilities, the high
      EphB4 expressing cells may be able to metastasize more readily.

PMID- 29368977
TI  - Quinazoline and quinazolinone as important medicinal scaffolds: a comparative
      patent review (2011-2016).
AB  - INTRODUCTION: Quinazoline and quinazolinone scaffolds represent an important
      class of biologically active nitrogen heterocyclic compounds. A variety of
      marketed drugs are based on these moieties. A diverse range of molecules with
      quinazoline/quinazolinone moieties have been reported to exhibit broad spectrum
      of biological activities. Area covered: This review covers recent efforts in the
      synthesis and biological screening of quinazoline/quinazolinone based compounds
      from 2011-2016. Expert opinion: Quinazoline and quinazolinones represent a
      diverse class of biologically active nitrogen heterocyclic compounds with immense
      therapeutic potential. Their ease of synthetic accessibility, and flexibility in
      structural modifications and functionalization further adds to their appeal in
      medicinal chemistry. A number of currently available drugs are based on
      quinazoline/quinazolinone scaffold. It is interesting to note that, among the
      recent patents available, a lot of them focus on the promising anticancer
      activity of quinazoline and quinazolinone containing compounds. However their
      biological activity is certainly not limited to anticancer only, they are also
      known to elicit a number of other biological and physiological effects in vitro
      and in vivo respectively. The interest in quinazolines and quinazolinones is ever
      growing, since they offer a fairly diverse chemical space for exploration of
      medicinal potential.

PMID- 29368979
TI  - Beyond static measures: A review of functional magnetic resonance spectroscopy
      and its potential to investigate dynamic glutamatergic abnormalities in
      schizophrenia.
AB  - Abnormalities of the glutamate system are increasingly implicated in
      schizophrenia but their exact nature remains unknown. Proton magnetic resonance
      spectroscopy (1H-MRS), while fundamental in revealing glutamatergic alterations
      in schizophrenia, has, until recently, been significantly limited and thought to
      only provide static measures. Functional magnetic resonance spectroscopy (fMRS),
      which uses sequential scans for dynamic measurement of a range of brain
      metabolites in activated brain areas, has lately been applied to a variety of
      task or stimulus conditions, producing interesting insights into neurometabolite
      responses to neural activation. Here, we summarise the existing 1H-MRS studies of
      brain glutamate in schizophrenia. We then present a comprehensive review of
      research studies that have utilised fMRS, and lastly consider how fMRS methods
      might further the understanding of glutamatergic abnormalities in schizophrenia.

PMID- 29368978
TI  - Experiences of a student-run clinic in primary care: a mixed-method study with
      students, patients and supervisors.
AB  - OBJECTIVE: To explore how a student-run clinic (SRC) in primary health care (PHC)
      was perceived by students, patients and supervisors. DESIGN: A mixed methods
      study. Clinical learning environment, supervision and nurse teacher evaluation
      scale (CLES + T) assessed student satisfaction. Client satisfaction questionnaire
      8 (CSQ-8) assessed patient satisfaction. Semi-structured interviews were
      conducted with supervisors. SETTING: Gustavsberg PHC Center, Stockholm County,
      Sweden. SUBJECTS: Students in medicine, nursing, physiotherapy, occupational
      therapy and psychology and their patients filled in questionnaires. Supervisors
      in medicine, nursing and physiotherapy were interviewed. MAIN OUTCOME MEASURES:
      Mean values and medians of CLES + T and CSQ-8 were calculated. Interviews were
      analyzed using content analysis. RESULTS: A majority of 199 out of 227 student
      respondents reported satisfaction with the pedagogical atmosphere and the
      supervisory relationship. Most of the 938 patient respondents reported
      satisfaction with the care given. Interviews with 35 supervisors showed that the
      organization of the SRC provided time and support to focus on the tutorial
      assignment. Also, the pedagogical role became more visible and targeted toward
      the student's individual needs. However, balancing the student's level of
      autonomy and the own control over care was described as a challenge. Many
      expressed the need for further pedagogical education. CONCLUSIONS: High student
      and patient satisfaction reported from five disciplines indicate that a SRC in
      PHC can be adapted for heterogeneous student groups. Supervisors experienced that
      the SRC facilitated and clarified their pedagogical role. Simultaneously their
      need for continuous pedagogical education was highlighted. The SRC model has the
      potential to enhance student-centered tuition in PHC. Key Points Knowledge of
      student-run clinics (SRCs) as learning environments within standard primary
      health care (PHC) is limited. We report experiences from the perspectives of
      students, their patients and supervisors, representing five healthcare
      disciplines. Students particularly valued the pedagogical atmosphere and the
      supervisory relationship. Patients expressed high satisfaction with the care
      provided. Supervisors expressed that the structure of the SRC supported the
      pedagogical assignment and facilitated student-centered tuition - simultaneously
      the altered learning environment highlighted the need for further pedagogical
      education. Student-run clinics in primary health care have great potential for
      student-regulated learning.

PMID- 29368981
TI  - Targeting autophagy blocks melanoma growth by bringing natural killer cells to
      the tumor battlefield.
AB  - Solid tumors are able to establish and sustain an immune suppressive
      microenvironment, which prevents the infiltration of cytotoxic effector immune
      cells into the tumor bed. We showed that genetic targeting of the
      macroautophagy/autophagy gene Becn1/Beclin1 in B16-F10 tumors inhibits their
      growth by inducing a massive infiltration of functional natural killer (NK) cells
      into the tumor bed. Such infiltration is primarily due to the ability of BECN1
      defective tumor cells to overexpress and release CCL5 cytokine in the tumor
      microenvironment by a mechanism involving the activation of the MAPK8/JNK-JUN/c
      Jun signaling pathway. Clinically, we reported a strong positive correlation
      between the expression of NK cell marker and CCL5 in human melanoma tumors and
      more importantly, a significant increased survival is found in melanoma patients
      expressing a high level of CCL5. Overall, these findings highlight the impact of
      targeting autophagy in breaking the immunosuppressive tumor microenvironment
      barrier, thus allowing the trafficking of cytotoxic NK cells into the tumor bed.
      This study underscore the importance of autophagy inhibition in tumors as a novel
      therapeutic strategy to fully exploit NK cells antitumor properties in clinical
      settings.

PMID- 29368982
TI  - RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are
      required for autophagy in murine ovarian cancer cells.
AB  - Among the 3 GTPases in the DIRAS family, DIRAS3/ARHI is the best characterized.
      DIRAS3 is an imprinted tumor suppressor gene that encodes a 26-kDa GTPase that
      shares 60% homology to RAS and RAP. DIRAS3 is downregulated in many tumor types,
      including ovarian cancer, where re-expression inhibits cancer cell growth,
      reduces motility, promotes tumor dormancy and induces macroautophagy/autophagy.
      Previously, we demonstrated that DIRAS3 is required for autophagy in human cells.
      Diras3 has been lost from the mouse genome during evolutionary re-arrangement,
      but murine cells can still undergo autophagy. We have tested whether DIRAS1 and
      DIRAS2, which are homologs found in both human and murine cells, could serve as
      surrogates to DIRAS3 in the murine genome affecting autophagy and cancer cell
      growth. Similar to DIRAS3, these 2 GTPases share 40-50% homology to RAS and RAP,
      but differ from DIRAS3 primarily in the lengths of their N-terminal extensions.
      We found that DIRAS1 and DIRAS2 are downregulated in ovarian cancer and are
      associated with decreased disease-free and overall survival. Re-expression of
      these genes suppressed growth of human and murine ovarian cancer cells by
      inducing autophagy-mediated cell death. Mechanistically, DIRAS1 and DIRAS2 induce
      and regulate autophagy by inhibition of the AKT1-MTOR and RAS-MAPK signaling
      pathways and modulating nuclear localization of the autophagy-related
      transcription factors FOXO3/FOXO3A and TFEB. Taken together, these data suggest
      that DIRAS1 and DIRAS2 likely serve as surrogates in the murine genome for
      DIRAS3, and may function as a backup system to fine-tune autophagy in humans.

PMID- 29368980
TI  - TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine
      kinase 1 inhibition.
AB  - The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the
      enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes
      important for the etiology of cancer. It has been suggested that SPHK1 levels are
      regulated by the tumor suppressor protein TP53, a key regulator of cell cycle
      arrest, apoptosis, and macroautophagy/autophagy. However, little is still known
      of the relationship between TP53 and SPHK1 activity in the regulation of these
      processes. To explore this link, we examined the effects of inhibiting SPHK1 in
      wild-type and TP53 null cancer cell lines. SK1-I, an analog of sphingosine and
      isozyme-specific SPHK1 inhibitor, suppressed cancer cell growth and clonogenic
      survival in a TP53-dependent manner. It also more strongly enhanced intrinsic
      apoptosis in wild-type TP53 cells than in isogenic TP53 null cells. Intriguingly,
      SK1-I induced phosphorylation of TP53 on Ser15, which increases its
      transcriptional activity. Consequently, levels of TP53 downstream targets such as
      pro-apoptotic members of the BCL2 family, including BAX, BAK1, and BID were
      increased in wild-type but not in TP53 null cells. Inhibition of SPHK1 also
      increased the formation of autophagic and multivesicular bodies, and increased
      processing of LC3 and its localization within acidic compartments in a TP53
      dependent manner. SK1-I also induced massive accumulation of vacuoles, enhanced
      autophagy, and increased cell death in an SPHK1-dependent manner that also
      required TP53 expression. Importantly, downregulation of the key regulators of
      autophagic flux, BECN1 and ATG5, dramatically decreased the cytotoxicity of SK1-I
      only in cells with TP53 expression. Hence, our results reveal that TP53 plays an
      important role in vacuole-associated cell death induced by SPHK1 inhibition in
      cancer cells.

PMID- 29368983
TI  - Endomembrane remodeling in autophagic membrane formation.
AB  - Autophagosomal membrane sources generate autophagic membrane precursors, which
      later assemble into the double-membrane autophagosome. The key events happening
      on the membrane sources during autophagic membrane generation remain poorly
      characterized. Our previous work found the ER-Golgi intermediate compartment
      (ERGIC) as a membrane source for the phagophore, the precursor to the
      autophagosome. A relocation of the COPII machinery from the ER-exit sites (ERES)
      to the ERGIC generates vesicles for LC3 lipidation. In recent work, we made a
      further step by showing that a starvation-induced remodeling of ERES facilitates
      the relocation of COPII to the ERGIC and the generation of the autophagic
      membrane.

PMID- 29368984
TI  - The reliability and validity of a designed setup for the assessment of static
      back extensor force and endurance in older women with and without hyperkyphosis.
AB  - OBJECTIVE: The purpose of this study was to investigate the intra-rater
      reliability and validity of a designed load cell setup for the measurement of
      back extensor muscle force and endurance. PARTICIPANTS: The study sample included
      19 older women with hyperkyphosis, mean age 67.0 +/- 5.0 years, and 14 older
      women without hyperkyphosis, mean age 63.0 +/- 6.0 years. METHODS: Maximum back
      extensor force and endurance were measured in a sitting position with a designed
      load cell setup. Tests were performed by the same examiner on two separate days
      within a 72-hour interval. The intra-rater reliability of the measurements was
      analyzed using intraclass correlation coefficient (ICC), standard errors of
      measurement (SEM), and minimal detectable change (MDC). The validity of the setup
      was determined using Pearson correlation analysis and independent t-test.
      RESULTS: Using our designed load cell, the values of ICC indicated very high
      reliability of force measurement (hyperkyphosis group: 0.96, normal group: 0.97)
      and high reliability of endurance measurement (hyperkyphosis group: 0.82, normal
      group: 0.89). For all tests, the values of SEM and MDC were low in both groups. A
      significant correlation between two documented forces (load cell force and target
      force) and significant differences in the muscle force and endurance among the
      two groups were found. CONCLUSION: The measurements of static back muscle force
      and endurance are reliable and valid with our designed setup in older women with
      and without hyperkyphosis.

PMID- 29368985
TI  - Noncanonical autophagy in dendritic cells triggers CNS autoimmunity.
AB  - Reactivation and expansion of myelin-reactive CD4+ T cells within the central
      nervous system (CNS) are considered to play a key role in the pathogenesis of
      multiple sclerosis (MS) and its animal model, experimental autoimmune
      encephalomyelitis (EAE). We demonstrated that accumulation of myelin-specific
      CD4+ T cells within the CNS and subsequent clinical disease development require
      autophagy related (ATG) protein-dependent phagocytosis in dendritic cells (DCs).
      Genetic ablation of this pathway impairs presentation of myelin-associated
      antigen following phagocytosis of injured, phosphatidylserine-exposing
      oligodendroglial cells. Thus, DCs use ATG-dependent phagocytosis for enhanced
      presentation of myelin antigen, thereby linking oligodendrocyte injury with
      antigen processing and T cell-pathogenicity during autoimmune CNS inflammation.

PMID- 29368986
TI  - Cholesterol and multilamellar bodies: Lysosomal dysfunction in GBA-Parkinson
      disease.
AB  - Lipid and cholesterol metabolism might play a role in the pathogenesis of
      Parkinson disease (PD). However, the association between cholesterol and PD is
      not clearly established. Cholesterol accumulation is closely related to the
      expression of multilamellar bodies (MLBs). Also, cholesterol controls
      autophagosome transport. Thus, impaired cholesterol and autophagosome trafficking
      might lead to robust autophagic vacuole accumulation. Our recent work provides
      the first evidence that the presence of the N370S GBA mutation produces an
      accumulation of cholesterol, which alters autophagy-lysosome function with the
      appearance of MLBs, rendering the cell more vulnerable and sensitive to
      apoptosis.

PMID- 29368987
TI  - Early Palliative Care and Its Impact on End-of-Life Care for Cancer Patients in
      Brazil.
AB  - BACKGROUND: Integrating palliative care into standard oncology care has been
      recommended for cancer patients. Early palliative care is associated with less
      aggressive treatment at the end of life. OBJECTIVE: To describe cancer patients
      receiving palliative care in Brazil, determining the time from entry into
      palliative care to death, and investigating whether late referral to palliative
      care is associated with aggressive end-of-life treatment. DESIGN: This was a
      cross-sectional study of cancer patients receiving palliative care in Brazil.
      SETTING/SUBJECTS: Subjects were 2985 cancer patients >=18 years of age who
      received at least two palliative care visits at the Sao Paulo State Cancer
      Institute, in the city of Sao Paulo, Brazil, and died between 2010 and 2013.
      MEASUREMENTS: We evaluated the time from the first palliative care consult to
      death, stratifying cases by the timing of entry into palliative care (>=3 or <3
      months before death). The associations between early palliative care and
      indicators of aggressive treatment were assessed by Pearson's chi-square test and
      Fisher's exact test. RESULTS: The overall median time between entry into
      palliative care and death was 34 days (mean, 72 days) and was significantly
      shorter in 2013 than in 2010 (p < 0.001). The number of emergency department
      visits was significantly lower among the patients who entered palliative care
      earlier (p < 0.001). CONCLUSIONS: Among cancer patients in Brazil, late referral
      to palliative care is common. Patients who enter palliative care earlier appear
      to receive less aggressive end-of-life treatment.

PMID- 29368988
TI  - Activities of Dual Combinations of Antibiotics Against Multidrug-Resistant
      Nontuberculous Mycobacteria Recovered from Patients with Cystic Fibrosis.
AB  - Patients with cystic fibrosis (CF) are at risk for recurrent pulmonary infections
      due to increased viscosity of airway secretions, leading to persistent
      colonization with pathogenic bacteria, including nontuberculous mycobacteria
      (NTM). Extensive antibiotic use for treatment of infections has led to increasing
      antimicrobial resistance, which is a significant barrier to the treatment of
      NTMs. We examined the in vitro activity of several antibiotics against a
      selection of the most drug-resistant clinical isolates of Mycobacterium
      abscessus, Mycobacterium chelonae, and Mycobacterium avium complex recovered from
      CF patients at our institution, as well as paired combinations of antibiotics
      against a subset of M. abscessus strains, to determine whether they exhibit
      synergy in inhibiting bacterial growth. Most isolates displayed resistance to at
      least six of the nine antibiotics tested for which phenotypic interpretation is
      available, and elevated minimum inhibitory concentrations (MICs) were observed
      for many of the other drugs. The major exception was clofazimine, which had
      relatively low MICs for most isolates across all species. When synergy testing
      was performed by using paired combinations of drugs, clofazamine and
      clarithromycin exhibited 100% synergy for all combinations tested, as did
      amikacin, with the exception of one isolate. These results suggest that
      synergistic antibiotic combinations are capable of overcoming drug resistance in
      vitro, and laboratories might consider implementation of synergy testing in
      multidrug-resistant (MDR)-NTM organisms to guide treatment decisions in the
      setting of extensive antimicrobial resistance.

PMID- 29368989
TI  - Attachment representations in sexually abused preschoolers: a comparative study.
AB  - Attachment theory provides a relevant framework for understanding the
      psychosocial adjustment of victims of child sexual abuse (CSA). However, most
      studies have been conducted among adult populations and none have focused on the
      impact of both preschoolers' and mothers' experience of sexual abuse on
      attachment security. The aim of this study was to compare attachment
      representations in sexually abused (n = 258) and non-abused preschoolers (n =
      133), and to explore the relation between maternal history of CSA and children's
      attachment representations. A story completion task assessing attachment
      representations was administered to children (Bretherton, Ridgeway, & Cassidy,
      1990). The results revealed that CSA preschoolers presented significantly higher
      levels of attachment disorganization compared to non-abused children, and that
      abused boys were at particular risk for hyperactivation and disorganization.
      Associations between mothers' history of CSA and children's attachment
      representations were non-significant. These findings support the need to consider
      victims' attachment representations in the implementation of efficient treatment
      programs. Targeting parent-child relationships in interventions could help
      promote attachment security in a vulnerable population of preschool victims.

PMID- 29368990
TI  - 'On December 1, 2015, sex changes. Forever': Pre-exposure prophylaxis and the
      pharmaceuticalisation of the neoliberal sexual subject.
AB  - The global scale-up of AIDS treatment initiatives during the first decade of the
      twenty-first century has been referred to as a kind of 'pharmaceuticalisation' of
      public health, a trend that is now building in the area of HIV prevention. This
      paper traces the emergence and increased uptake of pre-exposure prophylaxis
      (PrEP), antiretroviral medications that can keep HIV negative individuals from
      becoming infected, placing it within the broader (re)casting of HIV prevention as
      a medical and technological problem that has been central to the recent 'end of
      AIDS' discourse. While HIV prevention discourses have been grounded in a
      neoliberal calculus of individual responsibility since the late 1990s, PrEP
      constitutes a pharmaceutical extension of the responsibilised sexual subject.
      Central to this extension are the acknowledgment of one's risk and a willingness
      to take pre-emptive medical action to secure a future without HIV. For men who
      have sex with men, a population heavily targeted for biomedical interventions in
      the United States, PrEP marks a shift in moral discourses of what it means to be
      a responsible sexual subject. Characteristics of the pharmaceutical extension of
      the neoliberal sexual subject are explored through an examination of a New York
      City-based PrEP promotional campaign.

PMID- 29368991
TI  - Touching the dead: Autoethnographical reflections about the researcher's body in
      the field of death, dying, and bereavement.
AB  - This essay presents an account of the influence of the researcher's body within
      qualitative death research. It suggests that appropriate reflection on the
      researcher's subjectivity should consider his or her own bodily performances and
      experiences. At the beginning I offer some introductory thoughts in this regard,
      referring to Plessner's distinction between 'being a body' (Korper-haben) and
      'having a body' (Leib-sein). Here, I highlight the importance of autoethnographic
      approaches for the understanding of bodily experiences, such as sensations,
      perceptions and their aesthetics. To demonstrate the importance of considering
      the researcher's body within the research process, I then draw on my own
      autoethnographic material, discussing how I experienced in my body frightening
      and disturbing feelings while dealing with the dead. This material was collected
      during a six-month internship from April to September 2016 at a small funeral
      home in Thuringia, Germany. I explain how I was socialised regarding my bodily
      behaviour towards the dead years ago and how I acquired the knowledge that
      touching a corpse is often taboo; describe my bodily reactions when I saw a dead
      body for the first time during my internship and how these reactions influenced
      my fieldwork; relate how my senses and perceptions when first touching a corpse
      led to extreme responses that drew most of my attention to the haptic and sensual
      dimension, making me unable to notice other information in the field; and show
      how these bodily experiences crossed borders and influenced my life beyond my
      field research.

PMID- 29368993
TI  - An unusual case of noma caused by Klebsiella pnuemoniae and its management.
AB  - Noma or cancrum oris is an orofacial gangrene causing progressive mutilating
      destruction of the infected tissues. It mainly affects malnourished children with
      poor oral hygiene and concurrent debilitating systemic illnesses. It is a
      polymicrobial infection and borrelia vincentii and fusobacterium are the most
      important pathogens known. We present a case of a boy aged 2.5 years with noma
      where klebsiella was grown and was the initial cause of failure of empiric
      therapy.

PMID- 29368992
TI  - Characterization of an Outbreak of Extended-Spectrum beta-Lactamase-Producing
      Klebsiella pneumoniae in a Neonatal Intensive Care Unit in Italy.
AB  - Here we report an outbreak of extended spectrum beta-lactamase-producing
      Klebsiella pneumoniae that occurred in a neonatal intensive care unit in Northern
      Italy and involved 97 patients. Progressively tightened sets of containment
      measures were implemented but the epidemic event was stopped only 9 months later.
      The final, effective, containment strategy consisted of the application of strict
      geographic cohorting of colonized infants and their nursing staff, the suspension
      of any new admission and a rigorous daily sterilization protocol for all surfaces
      and fomites in the ward. A posteriori characterization of the outbreak strain was
      performed using both traditional microbiology and molecular biology techniques,
      and whole genome sequencing, allowing to compare outbreak isolates with other
      strains collected in the previous two years. The results allowed to determine
      that the outbreak strain had been circulating inside the ward since the year
      before. Genomic characterization revealed that the strain carried a wide array of
      virulence and antibiotic resistance determinants, including gene blaTEM-206,
      which had never been reported in a clinical isolate of K. pneumoniae before. The
      presence of such a high number of determinants for antibiotic resistance imposes
      significant therapeutic limitations on the treatment of infections, thus, further
      epidemiological investigations are needed to evaluate the prevalence of the newly
      described variant.

PMID- 29368994
TI  - Nurses' Intentions to Initiate an Antipsychotic or Behavioral Intervention with
      Nursing Home Residents: The Role of Norms and Being Evaluated.
AB  - OBJECTIVES: To examine whether exposure to a message to avoid antipsychotic
      medications and a salient sense of managerial oversight influenced nurses'
      treatment intentions. METHODS: 158 nurses from 28 long-term care facilities were
      randomized to one of four conditions within a 2 * 2 between-participants design.
      The nurses responded to a case study depicting a resident with dementia-related
      behavioral problems with their intent to initiate an antipsychotic or a
      psychosocial intervention. Self-efficacy, descriptive norms, and attitudes were
      measured via self-report. RESULTS: Perceived local antipsychotic prevalence was
      related to the nurses' treatment intentions. There were no main or interactive
      effects of the avoid antipsychotic or manager oversight conditions on the nurses'
      treatment intentions. However, there was a significant interaction of actual
      facility antipsychotic prevalence and the avoid antipsychotics message on
      intentions to initiate an antipsychotic. CONCLUSIONS: Nurses' perceptions of
      local antipsychotic prevalence were positively associated with intentions to
      initiate an antipsychotic and negatively associated with intentions to initiate a
      psychosocial intervention. However, a salient message to avoid antipsychotics had
      limited influence on nurses' treatment intentions and was associated with
      increased intentions to initiate antipsychotics in facilities with higher rates
      of antipsychotic use. The oversight condition did not demonstrate adequate
      internal validity, which may have caused its lack of effect on treatment
      intentions. CLINICAL IMPLICATIONS: Nurses' perceptions of the local prevalence of
      antipsychotic use is associated with their treatment intentions. However,
      increasing the visibility of a message discouraging antipsychotic use may have
      limited utility in influencing nurses' intentions to initiate an antipsychotic or
      psychosocial intervention.

PMID- 29368995
TI  - Rab GTPases, master controllers of eukaryotic trafficking.

PMID- 29368996
TI  - Iranian mothers' experiences of the outcomes of early motherhood: A qualitative
      study.
AB  - Early motherhood is a major health challenge in most developing countries. The
      aim of this study was to explore Iranian mothers' experiences of the outcomes of
      early motherhood. This qualitative study was done using the conventional
      inductive content analysis approach. A purposive sample of 18 Iranian mothers,
      with the experience of early motherhood, was recruited with maximum variation in
      terms of their age at their first pregnancy, their children's age, place of
      residence, and financial status. Data collection was done via in-depth
      semistructured interviews and continued up to data saturation. The MAXQDA
      software (v. 10.0) was employed for handling the data. Iranian mothers'
      experiences of the outcomes of early motherhood came into two main categories
      that were named "realization of the childhood dream of adulthood" and "heavy
      burden of adulthood on the small shoulders of childhood," The four subcategories
      of the first category were the acceleration of intellectual and mental
      maturation, strengthening of family relationships, developing a strong identity,
      and closer companionship with the child. The second main category also included
      four subcategories, namely, experiencing numerous difficulties, threats to
      mothers' physical and mental health, threats to children's health, and missing
      opportunities. Early motherhood is not merely a negative experience; rather it is
      also associated with different positive outcomes. Healthcare providers need to
      provide high-quality prenatal, perinatal, and postnatal care services to
      adolescent mothers and use available opportunities to strongly support them and
      their children.

PMID- 29368997
TI  - Suicide among men in Ghana: The burden of masculinity.
AB  - In Ghana, some studies have reported a high rate for both fatal and non-fatal
      suicidal behaviors among men. The current study aimed at understanding the
      psychosocial circumstances involved in male suicides. We interviewed between two
      to seven close relations of each of 12 men who died by suicide. Interpretative
      phenomenological analysis of data indicates that experiences of shame related to
      loss of economic control, breach of patriarchal norms, and threats to sexual
      competence contributed to the suicides. Addressing socioeconomic issues, creating
      opportunities for men to disclose their emotions, and identifying sources of
      these emotions may help prevent suicide among men.

PMID- 29368999
TI  - Corrigendum.

PMID- 29368998
TI  - A paradigm for understanding trust and mistrust in medical research: The
      Community VOICES study.
AB  - BACKGROUND: To promote justice in research practice and rectify health
      disparities, greater diversity in research participation is needed. Lack of trust
      in medical research is one of the most significant obstacles to research
      participation. Multiple variables have been identified as factors associated with
      research participant trust/mistrust. A conceptual model that provides meaningful
      insight into the interplay of factors impacting trust may promote more ethical
      research practice and provide an enhanced, actionable understanding of
      participant mistrust. METHODS: A structured survey was developed to capture
      attitudes toward research conducted in emergency situations; this article focuses
      on items designed to assess respondents' level of trust or mistrust in medical
      research in general. Community-based interviews were conducted in English or
      Spanish with 355 New York City residents (white 42%, African American 29%, Latino
      22%). RESULTS: Generally favorable attitudes toward research were expressed by a
      majority (85.3%), but many respondents expressed mistrust. Factor analysis
      yielded four specific domains of trust/mistrust, each of which was associated
      with different demographic variables: general trustworthiness (older age, not
      disabled); perceptions of discrimination (African American, Latino, Spanish
      language preference); perceptions of deception (prior research experience,
      African American); and perceptions of exploitation (less education). CONCLUSIONS:
      The four domains identified in the analysis provide a framework for understanding
      specific areas of research trust/mistrust among disparate study populations. This
      model offers a conceptual basis for the design of tailored interventions that
      target specific groups to promote trust of individual researchers and research
      institutions as well as to facilitate broader research participation.

PMID- 29369000
TI  - Cardiorespiratory repercussions according to the abdominal circumference
      measurement of men with obstructive respiratory disorder submitted to respiratory
      physiotherapy.
AB  - PURPOSE: To examine the effect of respiratory physiotherapy among men with
      obstructive respiratory disorder, in relation to abdominal circumference (AC).
      METHODS: Quasi-experimental study including 26 men split into two groups
      according to AC(cm): 1) < 102 (ACrisk-free); and 2) >= 102 (ACrisk). Heart rate
      variability (HRV), diastolic blood pressure (DBP), oxygen saturation (SpO2),
      FEV1/FVC, slow vital capacity (SVC), inspiratory capacity (IC), maximal
      inspiratory pressure (PImax), thoracoabdominal amplitude (AI) were measured:
      before (M1); 5 min after the physiotherapy (i.e. breathing exercises for airway
      clearance and active kinesiotherapy) (M2); and at follow-up, 30 min after
      physiotherapy (M3). RESULTS: The groups differed in age, body mass index and body
      fat %. At M2 IC was different between groups (ACrisk-free< ACrisk). There was an
      increase in HRV indexes, PImax, SpO2, axillary AI, FEV1/FVC, and reduction in HR
      for ACrisk-free. There was a decrease in AI and an increase in DBP for ACrisk.
      CONCLUSION: In men with obstructive respiratory disorder, increased AC
      measurement limited the thoracoabdominal expansibility and induced a rise of the
      DBP. Respiratory physiotherapy promotes an increase of cardiac modulation and
      inspiratory capacity for men with obstructive respiratory disorder.

PMID- 29369002
TI  - Reliability of sternal instability scale (SIS) for transverse sternotomy in lung
      transplantation (LTX).
AB  - : A surgical incision for bilateral sequential lung transplantation (BSLTX) is
      the "clam shell" (CSI) approach via bilateral anterior thoracotomies and a
      transverse sternotomy to allow for sequential replacement of the lungs. This can
      be associated with significant post-operative pain, bony overriding or sternal
      instability. The sternal instability scale (SIS) is a non-invasive manual
      assessment tool that can be used to detect early bony non-union or instability
      following CSI; however, its reliability is unknown. OBJECTIVE: This prospective
      blinded reliability study aimed to assess intra-rater and inter-rater reliability
      of the SIS following lung transplantation. METHOD: Participants post BSLTX aged
      older than 18 years underwent sternal assessment utilizing the SIS. Two assessors
      examined the sternum using a standardized protocol at two separate time points
      with a test-re-test time of 48 hours. The outcome measure was SIS tool using four
      categories from 0 (clinically stable) to 3 (separated sternum with overriding).
      RESULTS: In total, 20 participants (75% female) with a mean age of 48 years (SD
      17) and mean pain score of 3 out of 10 were included, 60% having well healed
      wounds and 25% reporting symptoms of sternal clicking. The most painful self
      reported painful activity was coughing. The SIS demonstrated excellent
      reliability with a kappa = 0.91 by different assessors on the same day, and kappa
      = 0.83 for assessments by the same assessor on different days. CONCLUSION: The
      SIS is a reliable manual assessment tool for evaluation of sternal instability
      after CSI following BSLTX and may facilitate the timely detection and management
      of sternal instability.

PMID- 29369001
TI  - iTRAQ-based proteomics analysis of autophagy-mediated immune responses against
      the vascular fungal pathogen Verticillium dahliae in Arabidopsis.
AB  - The mechanisms underlying the functional link between autophagy and plant innate
      immunity remain largely unknown. In this study, we investigated the autophagy
      mediated plant defense responses against Verticillium dahliae (V. dahliae)
      infection by comparative proteomics and cellular analyses. An assessment of the
      autophagy activity and disease development showed that autophagic processes were
      tightly related to the tolerance of Arabidopsis plant to Verticillium wilt. An
      isobaric tags for relative and absolute quantification (iTRAQ)-based proteomics
      analysis was performed, and we identified a total of 780 differentially
      accumulated proteins (DAPs) between wild-type and mutant atg10-1 Arabidopsis
      plants upon V. dahliae infection, of which, 193 ATG8-family-interacting proteins
      were identified in silico and their associations with autophagy were verified for
      several selected proteins. Three important aspects of autophagy-mediated defense
      against V. dahliae infection were revealed: 1) autophagy is required for the
      activation of upstream defense responses; 2) autophagy-mediated mitochondrial
      degradation (mitophagy) occurs and is an important player in the defense process;
      and 3) autophagy promotes the transdifferentiation of perivascular cells and the
      formation of xylem hyperplasia, which are crucial for protection against this
      vascular disease. Together, our results provide several novel insights for
      understanding the functional association between autophagy and plant immune
      responses.

PMID- 29369003
TI  - Clinical characteristics and prognosis in patients with a first acute heart
      failure hospitalization according to admission hyponatremia.
AB  - Objective Admission hyponatremia is related to poor outcomes in patients with
      heart failure (HF). Few studies have examined the influence of hyponatremia in
      the prognosis of HF patients without previous admissions. Our aim is to determine
      whether baseline hyponatremia predicts worse outcomes in a cohort of real-world
      HF patients admitted because of a first episode of acute HF. Methods We reviewed
      the medical records of 985 patients >50 years of age admitted within a two-year
      period for a first episode of decompensation of HF. We divided the sample
      according to the presence of hyponatremia, defined as serum sodium <135 mEq/L. We
      compared one-year all-cause mortality rates between groups, using Cox regression
      analyses. Results The patients' mean serum sodium at admission was 138 +/- 4; 150
      (15.2%) patients had hyponatremia. Hyponatremic patients had lower hematocrit
      values compared with the rest. Global mortality rates were higher across all
      evaluations (one, three, and 12 months) in the hyponatremia group, although
      statistical significance was not reached. After one year of follow-up no
      differences in patients' baseline sodium values were found between those who died
      and survivors (137.9 vs.138.6; p = 0.05). Natremia at admission considered as a
      continuous variable (HR 0.971; IC 95% 0.945-0.997) was associated with mortality;
      however, multivariate Cox regression analysis did not confirm this association.
      Conclusions Admission hyponatremia is not uncommon even in patients admitted for
      the first time because of acute HF. However, hyponatremia in this cohort of
      patients does not seem to influence significantly in short- to mid-term
      mortality.

PMID- 29369004
TI  - A modified Essen Stroke Risk Score for predicting recurrent ischemic stroke at
      one year.
AB  - Objective The Essen Stroke Risk Score (ESRS) is widely used to predict the risk
      of recurrent ischemic stroke but may not have sufficient discriminatory ability
      for predicting early recurrence. In this study, we developed a modified ESRS for
      predicting recurrent ischemic stroke at one year based on Chinese population.
      Methods Eight hundred and three consecutive patients were included in the study.
      We performed a univariate analysis to investigate the effect of previously
      identified risk factors on recurrent stroke at one year. The candidate predictors
      were included in a forward stepwise logistic regression model. Prediction scores
      were assigned based on beta coefficient and a modified ESRS system was
      constructed. We used receiver operating characteristic (ROC) curves to compare
      the predictive ability of the modified and original ESRS. Results Recurrent
      ischemic stroke occurred in 85 (11.00%) patients and death occurred in 68 (8.80%)
      patients within one year. Hypertension over 15 years, diabetes over 10 years,
      large artery atherosclerosis cerebral infarction by TOAST criteria and a history
      of transient ischemic attack (TIA) or ischemic stroke (IS) were identified as
      independent risk factors for recurrent stroke (all P < 0.05). The areas under the
      ROC curves of ESRS and modified ESRS were 0.58 (P < 0.05, 95%CI: 0.51-0.64) and
      0.70 (P < 0.05, 95% CI: 0.63-0.76), respectively. The modified ESRS appears to be
      superior to the original ESRS for predicting recurrent ischemic stroke at one
      year (P < 0.05). Conclusions The modified ESRS increased the ability of the
      original ESRS to predict recurrent stroke at one year among the Chinese
      population.

PMID- 29369005
TI  - Remote ischemic postconditioning protects the brain from focal
      ischemia/reperfusion injury by inhibiting autophagy through the mTOR/p70S6K
      pathway.
AB  - OBJECTIVE: Remote ischemic postconditioning (RIPostC) has been recognized as an
      applicable strategy for protecting against cerebral ischemia/reperfusion (I/R)
      injury. This study was performed to examine the effect of RIPostC on cerebral I/R
      and to explore its underlying mechanism. METHODS: Healthy male SD rats (N = 36)
      were assigned randomly into 3 groups of 12 each: sham group, I/R model group and
      RIPostC group. Animal models were performed by filament insertion for 2 h with
      middle cerebral artery occlusion(MCAO) followed by 24 h of reperfusion. RIPostC
      was induced by 15 min occlusion of femoral arteries followed by 15 min of
      reperfusion for 3 cycles at the beginning of middle cerebral artery reperfusion.
      The neurological deficits, infarct size and brain edema were determined.
      Autophagy was examined by transmission electron microscopy (TEM). The protein
      levels of microtubule-associated protein light chain 3 (LC3-II), mammalian target
      of rapamycin (mTOR), serine/threonine kinase p70S6 kinase (p70S6K), and their
      phosphorylation (p-mTOR and p-p70S6K) in the brain tissue of the rats were
      determined by western blotting. RESULTS: Our results suggested that RIPostC
      significantly reduced I/R-induced brain injury, as exhibited by a significantly
      decreased infarct size, mitigated brain edema and improved neurological deficits.
      RIPostC also significantly reduced the LC3-II/LC3-I ratio and protein expression
      of Beclin 1. Much less severe neuronal injury and fewer autophagosomes were
      observed by TEM in the RIPostC group. CONCLUSIONS: These results suggest that
      RIPostC attenuates cerebral I/R injury by inhibiting autophagy through the
      activation of the mTOR/p70S6K signaling pathway.

PMID- 29369006
TI  - Linear Energy Transfer Modulates Radiation-Induced NF-kappa B Activation and
      Expression of its Downstream Target Genes.
AB  - Nuclear factor kappaB (NF-kappaB) is a central transcription factor in the immune
      system and modulates cell survival in response to radiotherapy. Activation of NF
      kappaB was shown to be an early step in the cellular response to ultraviolet A
      (UVA) and ionizing radiation exposure in human cells. NF-kappaB activation by the
      genotoxic stress-dependent sub-pathway after exposure to different radiation
      qualities had been evaluated to a very limited extent. In addition, the resulting
      gene expression profile, which shapes the cellular and tissue response, is
      unknown. Therefore, in this study the activation of NF-kappaB after exposure to
      low- and high-linear energy transfer (LET) radiation and the expression of its
      target genes were analyzed in human embryonic kidney (HEK) cells. The activation
      of NF-kappaB via canonical and genotoxic stress-induced pathways was visualized
      by the cell line HEK-pNF-kappaB-d2EGFP/Neo L2 carrying the destabilized enhanced
      green fluorescent protein (d2EGFP) as reporter. The NF-kappaB-dependent d2EGFP
      expression after irradiation with X rays and heavy ions was evaluated by flow
      cytometry. Because of differences in the extent of NF-kappaB activation after
      irradiation with X rays (significant NF-kappaB activation for doses >4 Gy) and
      heavy ions (significant NF-kappaB activation at doses as low as 1 Gy), it was
      expected that radiation quality (LET) played an important role in the cellular
      radiation response. In addition, the relative biological effectiveness (RBE) of
      NF-kappaB activation and reduction of cellular survival were compared for heavy
      ions having a broad LET range (~0.3-9,674 keV/MUm). Furthermore, the effect of
      LET on NF-kappaB target gene expression was analyzed by real-time reverse
      transcriptase quantitative PCR (RT-qPCR). The maximal RBE for NF-kappaB
      activation and cell killing occurred at an LET value of 80 and 175 keV/MUm,
      respectively. There was a dose-dependent increase in expression of NF-kappaB
      target genes NF-kappaB1A and CXCL8. A qPCR array of 84 NF-kappaB target genes
      revealed that TNF and a set of CXCL genes (CXCL1, CXCL2, CXCL8, CXCL10), CCL2,
      VCAM1, CD83, NF-kappaB1, NF-kappaB2 and NF-kappaBIA were strongly upregulated
      after exposure to X rays and neon ions (LET 92 keV/MUm). After heavy-ion
      irradiations, it was noted that the expression of NF-kappaB target genes such as
      chemokines and CD83 was highest at an LET value that coincided with the LET
      resulting in maximal NF-kappaB activation, whereas expression of the NF-kappaB
      inhibitory gene NFKBIA was induced transiently by all radiation qualities
      investigated. Taken together, these findings clearly demonstrate that NF-kappaB
      activation and NF-kappaB-dependent gene expression by heavy ions are highest in
      the LET range of ~50-200 keV/MUm. The upregulated chemokines and cytokines
      (CXCL1, CXCL2, CXCL10, CXCL8/IL-8 and TNF) could be important for cell-cell
      communication among hit as well as nonhit cells (bystander effect).

PMID- 29369007
TI  - Combination therapy Eve and Pac to induce apoptosis in cervical cancer cells by
      targeting PI3K/AKT/mTOR pathways.
AB  - This study aimed to investigate the anti-cervical cancer effects of everolimus
      (Eve) and paclitaxel (Pac) when used alone or in combination. Human cervical
      cancer cells HeLa and SiHa were divided into four group: Blank control group
      (control), everolimus group (Eve), paclitaxel group (Pac) and combined therapy
      group (Eve + Pac). The cell viability was detected by CCK-8 assay and the cell
      cloning ability was detected by clonegenic assay. Flow cytometry was used to
      detect cell apoptosis. Meanwhile, the expression of phosphatidylinositol 3-kinase
      (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR) and their
      phosphorylated proteins were studied by western blot. The HeLa and SiHa cells
      proliferation and cloning ability were significantly inhibited in drug treatment
      groups compared with control group (p < .05), and the Eve + Pac combinatorial
      therapy showed the better results than single treatment with Eve or Pac.
      Combination of Eve and Pac has synergistic effect on the induction of apoptosis
      in cervical cancer cells. In addition, the protein ratios in HeLa and SiHa cell
      treated with the Eve + Pac combination were significantly lower than that of
      cervical cancer cells treated with either Eve or Pac cell alone. Our study
      suggested that Eve + Pac provide a novel therapeutic strategy for cervical
      cancer.

PMID- 29369008
TI  - Computational screening, ensemble docking and pharmacophore analysis of potential
      gefitinib analogues against epidermal growth factor receptor.
AB  - The observable mutated isoforms of epidermal growth factor receptor (EGFR) are
      important considerable therapeutic benchmarks in moderating the non-small cell
      lung cancer (NSCLC). Recently, quinazoline-based ATP competitive inhibitors have
      been developed against the EGFR; however, these imply the mutation probabilities,
      which contribute to the discovery of high probable novel inhibitors for EGFR
      mutants. Therefore, SAR-based bioactivity analysis, molecular docking and
      computational toxicogenomics approaches were performed to identify and evaluate
      new analogs of gefitinib against the ligand-binding domain of the EGFR double
      mutated model. From the diverse groups of molecular clustering and molecular
      screening strategies, top high-binding gefitinib-analogues were identified and
      studied against EGFR core cavity through three-phase ensemble docking approach.
      Resulted high possible leads showed good binding orientations than gefitinib
      (positive control) thus they were subjected to pharmacophore analysis that
      possesses possible molecular assets to tight binding with EGFR domain. Residues
      Ser720, Arg841 and Trp880 were observed as novel hot spots and involved in H
      bonds, pi-stacking and pi-cation interactions that contribute additional
      electrostatic potency to sustain stability and complexity of protein-ligand
      complexes, thus they have ability to profoundly adopted by pharmacophoric
      features. Furthermore, lead molecules have an inhibition percent probability,
      anticancer potency, toxic impacts, flexible pharmacokinetics, potential gene
      chemical interactions towards EGFR were revealed by computational systems biology
      tools. Our multiple screening strategies confirmed that the druggable sub-pocket
      was crucial to strong EGFR-ligand binding. The essential pharmacophoric features
      of ligands provided viewpoints for new inhibitors envisaging, and predicted
      scaffolds could used as anticancer agents against selected EGFR mutated isoforms.

PMID- 29369009
TI  - Characterization of free fatty acid receptors expression in an obesity rat model
      with high sucrose diet.
AB  - INTRODUCTION/AIMS: In recent years, it has been shown that free fatty acids
      receptors (FFAR) of whose function in the cell surface plays a significant role
      in the regulation of cell function and nutrition as well are activated by various
      endogenous ligands, but mainly by fatty acids. Within FFAR of our interest are
      GPR 41, 43 and 120. The functions of these receptors are varied and dependent on
      the tissue where they are. The activation and signaling of these receptors, FFAR,
      are involved in many physiological processes, and currently the target of many
      drugs in metabolic disorders like obesity, diabetes and atherosclerosis. MATERIAL
      AND METHODS: Obesity was induced with hypercaloric diet (HD) in male Wistar rats
      for 20 weeks (n = 10). At the end, adipose tissue (abdominal and subcutaneous)
      was taken to perform assays for relative quantification mRNA expression by end
      point RT-PCR and protein level expression by Western blot. RESULTS: These present
      data have shown for the first time that total mRNA isolation and protein
      expression from both adipose tissues (abdominal and subcutaneous) of rat in
      obesity condition yield significative statistical difference among the control
      versus obese groups, showing that the diet high in carbohydrates modifies the
      total presence of mRNA and protein level expression of the receptors GPR41, 43
      and 120. CONCLUSIONS: Further comparative methods are in process to clarify
      whether or not the obesity changes the functional receptors in these two tissues
      for new pharmacological approaches.

PMID- 29369010
TI  - Effects of LPA1 and LPA6 on the regulation of colony formation activity in colon
      cancer cells treated with anticancer drugs.
AB  - Lysophosphatidic acid (LPA) is a simple physiological lipid and exhibits a
      variety of cellular responses via the activation of G protein-coupled
      transmembrane LPA receptors (LPA receptor-1 (LPA1) to LPA6). The aim of our study
      was to investigate effects of LPA receptors on soft agar colony formation in
      colon cancer cells treated with anticancer drugs. DLD1 cells were treated with
      fluorouracil (5-FU) or cisplatin (CDDP) for at least six months (DLD-5FU and DLD
      CDDP cells, respectively). LPAR1 gene expression was markedly elevated in DLD-5FU
      cells. In contrast, DLD-CDDP cells showed the high expression of LPAR6 gene. In
      colony formation assay, DLD-5FU cells formed markedly large-sized colonies, while
      no colony formation was observed in DLD1 and DLD-CDDP cells. The large-sized
      colonies formed in DLD-5FU cells were suppressed by LPA1 knockdown. In contrast,
      LPA6 knockdown increased the size of colonies. In addition, DLD-5FU cells were
      further treated with CDDP for three months (DLD-C-F cells). DLD-CDDP cells were
      also treated with 5-FU (DLD-F-C cells). DLD-C-F cells formed large-sized
      colonies, but not DLD-F-C cells, correlating with LPAR1 and LPAR6 gene expression
      levels. These results suggest that LPA1 and LPA6 may regulate the colony
      formation activity in DLD1 cells treated with anticancer drugs.

PMID- 29369011
TI  - Structural insights of Staphylococcus aureus FtsZ inhibitors through molecular
      docking, 3D-QSAR and molecular dynamics simulations.
AB  - Filamentous temperature-sensitive protein Z (FtsZ) is a protein encoded by the
      FtsZ gene that assembles into a Z-ring at the future site of the septum of
      bacterial cell division. Structurally, FtsZ is a homolog of eukaryotic tubulin
      but has low sequence similarity; this makes it possible to obtain FtsZ inhibitors
      without affecting the eukaryotic cell division. Computational studies were
      performed on a series of substituted 3-arylalkoxybenzamide derivatives reported
      as inhibitors of FtsZ activity in Staphylococcus aureus. Quantitative structure
      activity relationship models (QSAR) models generated showed good statistical
      reliability, which is evident from r2ncv and r2loo values. The predictive ability
      of these models was determined and an acceptable predictive correlation (r2Pred)
      values were obtained. Finally, we performed molecular dynamics simulations in
      order to examine the stability of protein-ligand interactions. This facilitated
      us to compare free binding energies of cocrystal ligand and newly designed
      molecule B1. The good concordance between the docking results and comparative
      molecular field analysis (CoMFA)/comparative molecular similarity indices
      analysis (CoMSIA) contour maps afforded obliging clues for the rational
      modification of molecules to design more potent FtsZ inhibitors.

PMID- 29369012
TI  - Executive functioning and processing speed in age-related differences in time
      estimation: a comparison of young, old, and very old adults.
AB  - Age-related differences in time estimation were examined by comparing the
      temporal performance of young, young-old, and old-old adults, in relation to two
      major theories of cognitive aging: executive decline and cognitive slowing. We
      tested the hypothesis that processing speed and executive function are
      differentially involved in timing depending on the temporal task used. We also
      tested the assumption of greater age-related effects in time estimation in old
      old participants. Participants performed two standard temporal tasks: duration
      production and duration reproduction. They also completed tests measuring
      executive function and processing speed. Findings supported the view that
      executive function is the best mediator of reproduction performance and inversely
      that processing speed is the best mediator of production performance. They also
      showed that young-old participants provide relatively accurate temporal judgments
      compared to old-old participants. These findings are discussed in terms of
      compensation mechanisms in aging.

PMID- 29369013
TI  - Children's perspectives on the benefits and burdens of research participation.
AB  - BACKGROUND: Participation in research is associated with benefits and burdens for
      individual research participants. Children living with a chronic illness are
      considered particularly vulnerable as they are already burdened with symptoms of
      their illness. In particular contexts, such as learning health care systems
      (LHS), where research and clinical care are integrated, children with chronic
      illnesses may be asked to participate in research related to their illness. A
      growing body of literature has focused on children's perspectives as research
      subjects; however, a relatively understudied aspect concerns children's
      experiences of research in clinics where they are also patients. METHODS: We
      interviewed 25 Canadian children and adolescents living with inflammatory bowel
      disease (IBD) about their experiences of research participation. RESULTS: Our
      participants described aspects of the research process and particular experiences
      as benefits and others as burdens. Benefits included helping others, receiving
      incentives, receiving the results of previous studies, and participating in fun
      activities. Burdens included the time required for particular types of research,
      physical and psychological discomfort, and feelings of obligation. CONCLUSIONS:
      Our study describes the experiences of children participating in research at a
      site that integrates research and clinical care. Our participants described
      experiences that often go unreported (such as feelings of obligation); we mention
      these as important considerations to be mindful of when interacting with children
      as (potential) research participants in an LHS and when thinking about research
      ethics protocols or the assent/consent process.

PMID- 29369014
TI  - The categorization of amateur cyclists as research participants: findings from an
      observational study.
AB  - Sampling bias is an issue for research involving cyclists. The heterogeneity of
      cyclist populations, on the basis of skill level and riding purpose, can generate
      incorrect inferences about one specific segment of the population of interest. In
      addition, a more accurate categorization would be helpful when physiological
      parameters are not available. This study proposes using self-reported data to
      categorize amateur cyclist types by varying skill levels and riding purposes,
      therefore improving sample selection in experimental studies. A total of 986
      cyclists completed an online questionnaire between February and October 2016. Two
      step cluster analyses were performed to generate distinct groups, and dependent
      variables of these groups were compared (demographics and characteristics of
      cycling practice). The cluster analysis relied on 4 descriptors (cycling weekly
      volume, average cycling speed, riding purpose, and cycling discipline) and
      yielded five distinct groups: competitive road, recreational road, competitive
      mountain bike (MTB), recreational MTB and competitive triathlon. Among these
      groups, averages and distributions for age, height, body mass, body mass index,
      training volume and intensity, and years of experience varied. This
      categorization can potentially help researchers recruit specific groups of
      cyclists based upon self-reported data and therefore better align the sample
      characteristic with the research aims.

PMID- 29369015
TI  - Developmental biology in bioartificial tissue design: manufacturing and
      regulatory considerations.

PMID- 29369016
TI  - Use of quantitative ultrasound as bone mineral density evaluation in an Italian
      female population living with HIV: A real-life experience.
AB  - This is a multicenter cross-sectional study where we aimed to detect the rate of
      osteopenia/osteoporosis in an HIV female population (WLWHIV) by means of "heel
      quantitative ultrasound" (QUS) measurement. We enrolled 273 patients, mean age
      48.1 years, 36% menopausal, 96% on combination antiretroviral therapy (cART).
      Calcaneal measure of bone mass index by QUS revealed osteopenia and osteoporosis
      in 76 (27.8%) and 16 (5.9%) WLWHIV. Our data underline the correlation between
      low QUS parameters and traditional risk factors for osteoporosis rather than with
      cART exposure, thus suggesting the crucial importance of detection and correction
      of traditional risk factors for osteoporosis in WLWHIV.

PMID- 29369017
TI  - Quantitative Analysis of Aedes albopictus Movement Behavior Following Sublethal
      Exposure To Prallethrin.
AB  - The pyrethroid prallethrin, an AI in DUETTM (Clarke Mosquito Control, St.
      Charles, IL), is widely marketed ultra-low volume (ULV) mosquito adulticide.
      Volatilized prallethrin is intended to stimulate mosquito flight, increasing its
      adulticide effectiveness. However, field tests using volatilized prallethrin have
      not produced significant differences in mosquito trap catches, leading to
      questions regarding prallethrin's behavioral impact efficacy. Thus, we conducted
      laboratory tests of prallethrin's effect on flight behavior of adult female Asian
      tiger mosquitoes, Aedes albopictus. Mosquitoes were divided into 3 groups:
      untreated control, exposed to volatilized prallethrin, and exposed to a liquid
      spray calibrated to simulate a ULV application at label rates. After exposure,
      mosquito behavior in an airstream of 0.5 m/sec was recorded and analyzed using
      motion-tracking software. No significant differences in flight behavior were
      found between the control and treated mosquitoes exposed to volatilized
      prallethrin. The ULV-sprayed mosquitoes exhibited a significant increase in the
      number of flight events, the turning frequency, overall movement speed, and
      flight speed compared to the control-a significant difference in locomotor
      stimulation response that would increase exposure to a ULV spray cloud. However,
      our results showed that volatilization alone was insufficient to increase ULV
      efficacy in the field and suggested that incorporating a more volatile flight
      stimulant into ULV adulticides would provide a measurable improvement in mosquito
      control.

PMID- 29369018
TI  - Vector Competence of Some Mosquito Species From Canada For Zika Virus.
AB  - The recent introduction of Zika virus (ZIKV) into the Americas and the occurrence
      of birth defects associated with infection during pregnancy have created a
      concern about the spread of this virus into more northern countries in the
      Americas. Therefore, we examined several species of mosquitoes found in southern
      Manitoba, Canada, for their susceptibility to infection and their ability to
      transmit ZIKV. Aedes cinereus, Ae. euedes, Ae. fitchii, Ae. sticticus, Ae.
      vexans, Coquillettidia perturbans, Culex restuans, and Cx. tarsalis were captured
      in the vicinity of Winnipeg, Manitoba; brought to the laboratory; and allowed to
      feed on a ZIKV-sheep blood suspension to determine oral susceptibility. In
      addition, some of the nonfed individuals were inoculated intrathoracically to
      examine for the presence of a salivary gland barrier. Despite ingesting blood
      containing 105.4 plaque-forming units/ml, infection rates were very low, and
      infected individuals were only detected for Ae. vexans. Transmission was observed
      for Ae. vexans, Cq. perturbans, and Cx. restuans that had been inoculated with
      ZIKV, although rates were low. Based on the extremely low vector competence found
      in this study and the lack of a preferential feeding on humans, it is unlikely
      than any of the mosquito species tested in this study would be involved in any
      large-scale transmission of ZIKV in Canada.

PMID- 29369019
TI  - Effectiveness of Five Products To Control Culex pipiens Larvae In Urban
      Stormwater Catch Basins.
AB  - Effectiveness in controlling mosquito larvae in stormwater catch basins in the
      North Shore Mosquito Abatement District (northeastern Cook County, IL) was
      determined for 2 extended-duration larvicides indicating up to 180 days of
      control on their labels (NatularTM XRT, FourStar(r) Briquet) and 3 larvicides
      indicating up to 30 days of control (NatularTM T30, NatularTM G30, and
      VectoLex(r) FG). Over the course of the 26-wk study, catch basins receiving the
      extended-release products were treated twice (an initial treatment in early April
      followed by a re-treatment after 16 wk), and catch basins receiving the shorter
      duration products were treated every 28 days, with the 1st treatment occurring
      during the 1st week in April. Control in an individual catch basin was considered
      to have failed if late-stage larvae or pupae were found in 2-dip samples taken
      from the catch basin. Control for a treatment was considered to have failed if
      >25% of catch basins treated with the product failed at a given time period
      posttreatment. All of the products evaluated in the study demonstrated some
      degree of control; however, the Natular XRT-, FourStar Briquet-, and Natular T30
      treated basins rarely achieved the effectiveness threshold of <=25% of catch
      basins failing. By comparison, basins treated with Natular G30 were below that
      threshold for 3 of 4 wk every treatment round and VectoLex(r) FG was consistently
      below that threshold for all 4 wk posttreatment for every treatment round.
      Compared with untreated catch basins, the total season pupal production was
      reduced by approximately 48% in the Natular XRT-, FourStar Briquet-, and Natular
      T30-treated basins, and by 87% and 99% in the Natular G30- and VectoLex FG
      treated basins, respectively. Operational quality control observations indicated
      that effective control (i.e., <=25% of catch basins failing) ranged from 3 to 12
      wk posttreatment for catch basins treated with Natular XRT and from 5 to 9 wk
      with VectoLex FG, and that there was considerable geographic variation in the
      duration of effectiveness. The results indicate that 30-day re-treatments with
      granular formulations in difficult-to-control areas may provide a more cost
      effective outcome than using 1 or 2 applications of extended-duration larvicides.

PMID- 29369020
TI  - Relative Insecticidal Efficacy of Three Spatial Repellent Integrated Light
      Sources Against Aedes aegypti.
AB  - Three repellent products, OFF! Mosquito Lamp, Insecticandel, and Rescue
      DecoShield, were comparatively evaluated against Aedes aegypti in 130-m2 enclosed
      areas with a 317-m3 air volume. The results showed that the OFF! Mosquito Lamp
      with metofluthrin had a greater effect than the Insecticandel with transfluthrin,
      which had greater effect than the DecoShield with lemongrass oil and several
      other plant oils against Ae. aegypti. The OFF! Mosquito Lamp was the only product
      to exceed 50% mortality. An outdoor semi-field evaluation was conducted to
      determine the effect by distance of the product. Mosquitoes were stationed in
      cages at 3, 6, 9, 12, and 15 m away from the treatment in a downwind linear array
      and exposed for 10 min. They were recorded for knockdown after treatment and at
      24 h for mortality. The OFF! Mosquito Lamp produced 100% mortality indoors and
      >80% knockdown and 90% mortality within 6 m while outdoors against Ae. aegypti.

PMID- 29369021
TI  - First Record of Aedes japonicus In Florida.
AB  - The presence of Aedes j. japonicus in Florida is reported for the first time.
      Four adult females were collected by a Mosquito Magnet(r) X trap baited with
      pressurized CO2 in Okaloosa County, FL, in August 2012 and later identified as
      Ae. japonicus in 2014. Additional adult and larval specimens were collected
      during 2014-17 from Bay, Leon, Okaloosa, Santa Rosa, or Walton counties, Florida.
      Notes are provided on the location, general habitats, and mosquito associates
      that may be found with Ae. japonicus in northwestern Florida. The role of Ae.
      japonicus in arbovirus transmission within Florida is currently unknown and
      should be further explored.

PMID- 29369022
TI  - First Record of Culex coronator In Shelby County, Tennessee.
AB  - Culex coronator has been identified in Shelby County, TN, for the first time as
      an established species. This is an important discovery since the range of Cx.
      coronator is unknown in Tennessee and it has been found positive for West Nile
      virus. Larvae and an adult were discovered during routine surveillance. Larvae
      were collected at 9 different locations, while the 1 adult captured was at the
      10th isolated location.

PMID- 29369023
TI  - Field Trial To Evaluate Two Different Procedures For Monitoring the Efficacy of
      Aquatain(r) Against Culex pipiens and Aedes albopictus IN CATCH BASINS.
AB  - Aedes albopictus and Culex pipiens are commonly distributed in Italy and
      represent the main species found in catch basins. The application of a silicone
      based film (e.g., Aquatain(r)) is a new tool recently introduced for treating
      catch basins. While the efficacy of Aquatain has been experimentally
      demonstrated, its use is still lacking an appropriate monitoring procedure. The
      present study compared the differences in the efficacy of treatment assessment
      between a newly developed floating system (FS), which was designed to collect
      emerging adults, with the standard dipper procedure, used for estimating the
      abundance of mosquito larvae. Forty catch basins, half treated with Aquatain and
      half untreated (control basins), were monitored weekly using dipper (10 treated +
      10 control basins) or FS (10 + 10) 5 times after 2 subsequent treatments. Both
      monitoring procedures recorded high percentages of larvae and adult reduction for
      the 1st 1-3 wk after treatments, confirming the simultaneous activity of Aquatain
      against all stages of mosquitoes. Differences in adult emergence were recorded
      also when monitoring of larvae was ineffective, suggesting that the newly
      developed FS is a promising method for assessing the efficacy of monomolecular
      films in catch basins.

PMID- 29369024
TI  - Diversity of Mosquitoes At the Itatiaia National Park, State of Rio De Janeiro,
      Brazil.
AB  - A temporal observational study was conducted with the aim of characterizing
      Culicidae richness, diversity, abundance, and species similarity in fragments of
      Atlantic Forest within the Itatiaia National Park, state of Rio de Janeiro,
      Brazil. A total of 31 mosquito species were collected in 2 sampling stations,
      during the day and night, and the abundance index and dominance coefficient for
      each species were calculated. The results showed that the culicid density was
      higher during the day, and the time preference was directly influenced by the
      climate variables analyzed, which acted as limiting factors for mosquito
      occurrence. The mosquito fauna at the Itatiaia National Park presented high
      richness, including some epidemiologically important species: Anopheles cruzii,
      Haemagogus leucocelaenus, Aedes scapularis, and Sabethes identicus. Studies of
      this region supply information on biodiversity, and consequently help to
      understand epidemiological aspects of potential pathogen vector species.

PMID- 29369028
TI  - Laboratory Evaluation of Synthetic Blends of l-(+)-Lactic Acid, Ammonia, and
      Ketones As Potential Attractants For Aedes aegypti.
AB  - Attraction of Aedes aegypti to various binary, trinary, and quaternary blends of
      lactic acid and ketones with or without ammonia was studied using a dual choice
      olfactometer. A dose dependent attraction was observed in cases of single
      compounds where cyclopentanone attracted the highest percentage (36.9 +/- 1.8%)
      of Ae. aegypti when tested alone. No significant difference was observed between
      the attraction levels of trinary and binary blends of lactic acid and acetone or
      butanone when tested against clear air. However, in competitive bioassays, the
      trinary blend of lactic acid, acetone, and butanone was significantly preferred
      over binary blends of individual compounds ( P < 0.05). Acetylacetone was weakly
      attractive when tested alone but showed additive attraction when blended with
      lactic acid. However, acetylacetone acted as an attraction inhibitor when blended
      with other compounds. Cyclopentanone was attractive, but enhancement of
      attraction was not observed when blended with other components. Addition of
      ammonia to binary or trinary blends of lactic acid, acetone, and/or butanone did
      not increase the attraction significantly. In competitive bioassays, the blends
      containing ammonia were significantly preferred over the blends lacking ammonia (
      P < 0.05). This highlights ammonia as an essential component of synthetic blends.
      A quaternary blend of lactic acid, ammonia, acetone, and butanone was most
      attractive (65 +/- 1.5%) and preferred blend of all other combinations.

PMID- 29369029
TI  - BG-SentinelTM Trap Efficacy As A Component of Proof-Of-Concept For Push-Pull
      Control Strategy For Dengue Vector Mosquitoes.
AB  - The efficacy of the BG-SentinelTM (BGS) trap as a "pull" component of a "push
      pull" system (PPS) for management of the dengue vector, Aedes aegypti, was
      evaluated using local households in Pu Tuey, Kanchanaburi, Thailand. The pull
      component was the concluding phase of a 3-part investigation using a PPS
      combination spatial repellent (SR) and BGS trap to capture adult vector
      mosquitoes. Two sentinel households were selected for evaluation of BGS trap
      efficacy based on the highest pretrial indoor resting densities of Ae. aegypti
      using Centers for Disease Control and Prevention (CDC) mechanical backpack
      collections. Potential Ae. aegypti resting sites around the selected houses were
      identified as possible competing sites that might influence the BGS trap capture
      efficiency. Results showed that BGS traps were productive in capturing Ae.
      aegypti females (93.4% of all Aedes collected) in the presence of competing man
      made, artificial resting sites. The CDC backpack aspirator collections provided
      an indirect measure of local Aedes population, although technically not
      comparable for supporting productivity of BGS traps due to different collection
      days and households sampled. The predominant competing resting sites were water
      containers found within 3 m around the outside of sentinel households. The most
      productive BGS collections between houses differed by location. The most
      productive period of operation for Ae. aegypti BGS trapping was between 1330 and
      1730 h. The BGS trap appears an effective "pull" device in the PPS strategy in
      natural settings.

PMID- 29369031
TI  - Comparison of Adult Mosquito Abundance From Biogents-2 Sentinel and Biogents
      Gravid Aedes Traps In Northeastern Florida.
AB  - We compared the efficacy of the Biogents Gravid Aedes Trap (BG-GAT) and Biogents
      2 Sentinel (BG2S) trap to assess differences in adult mosquito collection rates
      between these 2 mosquito surveillance methods in northeastern Florida. Species
      diversity of trap collections was significantly greater for BG2S than for BG-GAT,
      with 14 mosquito species collected from the former trap and 4 species from the
      latter. Aedes aegypti and Culex quinquefasciatus were the 2 predominant species
      collected in both traps. Overall, BG2S traps collected significantly more
      mosquitoes (in some instances nearly 5 times) than the BG-GAT, regardless of
      species. There was no significant difference between the 2 traps with respect to
      gravid status when total species and number of mosquitoes collected were
      compared. However, at the species level, 8% of Ae. aegypti were gravid from the
      BG-GAT collections compared with 1% from the BG2S. The number of gravid Cx.
      quinquefasciatus was also considerably greater (59%) for the BG-GATs than for
      BG2S traps (2%), but these relationships were not statistically significant due
      to high variability in collections between traps.

PMID- 29369032
TI  - A Small-Scale Investigation Into the Effect of A Larvicidal Oil On Oviposition
      Site Preference By Aedes aegypti.
AB  - Larvicidal oils can be used to control immature Aedes aegypti and other
      pestiferous mosquitoes. To test whether oil-based larvicides also act as
      oviposition deterrents, indoor and semi-field trials were conducted at the Navy
      Entomology Center of Excellence in Jacksonville, FL. In both studies, treatment
      cages consisted of oviposition cups lined with seed germination paper as an
      oviposition substrate and filled with 1-wk-old southern live oak ( Quercus
      virginiana) leaf litter-infused water. Treatment cages consisted of 2 cups
      treated with CocoBearTM Mosquito Larvicidal Oil, while 2 cups were untreated.
      Control cages contained oviposition cups with only oak leaf litter-infused water.
      Gravid Ae. aegypti were released into cages and allowed to oviposit for 24 h,
      after which eggs were counted. The number of eggs deposited in treatment and
      control cages was not significantly different (indoor P = 0.0865; outdoor P =
      0.9765). However, the number of eggs deposited in untreated cups was
      significantly greater than that deposited in treated cups within treatment cages
      (indoor P < 0.0001; outdoor P = 0.0050). These results suggest that the presence
      of the larvicidal oil CocoBear may cause gravid female Ae. aegypti to seek
      alternative oviposition sites.

PMID- 29369033
TI  - Preliminary Results On the Efficacy of Macroalgal Extracts Against Larvae of
      Aedes albopictus.
AB  - Activity of ethanolic extracts of the algae Ulva rigida, Asparagopsis taxiformis,
      Dictyota dichotoma, and Cystoseira barbata, collected along Italian coasts, was
      tested against larvae of the Asian tiger mosquito ( Aedes albopictus), a vector
      of pathogens for animals and humans. Tests were carried out using 10 specimens of
      3rd-stage larvae per test, following the World Health Organization standard
      protocol with minor modifications. Among algal extracts, only D. dichotoma was
      active against the larvae of Ae. albopictus. Ethanolic extracts of that species
      showed LC90 (the concentration that kills 90% of larvae) and LC50 (the
      concentration that kills 50% of larvae) values at 44.32 and 85.92 mg/liter,
      respectively. Based on the data obtained, D. dichotoma biometabolic extracts
      could be potential candidates as larvicide compounds to control Ae. albopictus,
      encouraging the use of macroalgae as natural resources in integrated vector
      management strategies.

PMID- 29369034
TI  - Regional Survey of Mosquito Control Knowledge and Usage In North Carolina.
AB  - Mosquitoes are a nuisance and can transmit pathogens to humans and other animals,
      resulting in notable morbidity and mortality. Organized mosquito control programs
      conduct surveillance, source reduction, treatment of mosquito oviposition sites,
      and adulticiding to protect public health. However, in some regions, there has
      been a decline in county and municipal mosquito control programs, and homeowners
      increasingly contract with private mosquito control companies or address mosquito
      related issues themselves at the household level. The extent to which these
      services are being used, the potential for mosquito and/or insecticide exposure
      around the home, and the access to these services by individuals of different
      socioeconomic categories are not known. We conducted regional (western, central,
      eastern) assessments of public perception and knowledge of mosquito control
      services in a variety of communities of different socioeconomic categories (low,
      moderate, high) and types (urban, suburban, rural) in 3 North Carolina counties.
      We also assessed the respondents' basic knowledge of mosquito-borne diseases.
      Most respondents thought mosquito control was important to protect against both
      nuisance mosquitoes and mosquito-borne disease. The majority of people would pay
      <=$50/year for mosquito control and most thought this should be covered by
      municipal/county taxes. Many respondents (31%, 95% confidence interval [CI] 26
      35%) personally undertake mosquito control on their properties, but only 5.3%
      (95% CI 3.1-7.5%) contract with professional mosquito control services, with no
      significant differences between region, community type, or socioeconomic category
      in the proportion using private mosquito control services. While there were
      significant differences between factor levels (3 regions, 3 community types, 3
      socioeconomic categories) in some responses, there were no significant
      differences observed between respondents, regardless of factor level, in the
      willingness to contribute funds to a community-based mosquito control program.

PMID- 29369035
TI  - Identification of Differentially Expressed Genes In Deltamethrin-Resistant Culex
      pipiens quinquefasciatus.
AB  - Culex quinquefasciatus is one of China's major house-dwelling mosquito species
      and an important vector of filariasis and encephalitis. Chemical treatments
      represent one of the most successful approaches for comprehensive mosquito
      prevention and control. However, the widespread use of chemical pesticides has
      led to the occurrence and development of insecticide resistance. Therefore, in
      depth studies of resistance to insecticides are of vital importance. In this
      study, we performed a gene expression analysis to investigate genes from Cx.
      quinquefasciatus that may confer pyrethroid resistance. We aimed to understand
      the mechanisms of Cx. quinquefasciatus resistance to pyrethroid insecticides and
      provide insights into insect resistance management. Using a resistance bioassay,
      we determined the deltamethrin LC50 values (lethal concentration required to kill
      50% of the population) for Cx. quinquefasciatus larvae in the F21, F23, F24, F26,
      F27, and F30 generations. The 7 tested strains exhibited pesticide resistance
      that was 25.25 to 87.83 times higher than that of the SanYa strain. Moreover, the
      expression of the OBPjj7a (odorant-binding protein OBPjj7a), OBP28 (odorant
      binding protein OBP28), and E2 (ubiquitin-conjugating enzyme) genes was
      positively correlated with deltamethrin resistance ( R2 = 0.836, P = 0.011; R2 =
      0.788, P = 0.018; and R2 = 0.850, P = 0.009, respectively) in Cx.
      quinquefasciatus. The expression of 4 additional genes, H/ACA, S19, SAR2, and
      PGRP, was not correlated with deltamethrin resistance. In summary, this study
      identified 3 Cx. quinquefasciatus genes with potential involvement in
      deltamethrin resistance, and these results may provide a theoretical basis for
      the control of mosquito resistance and insights into resistance detection.

PMID- 29369036
TI  - Molecular Identification of Four Members of the Anopheles dirus Complex Using the
      Mitochondrial Cytochrome C Oxidase Subunit I Gene.
AB  - Precise mosquito species identification is an essential step for proper
      management and control of malaria vectors. Misidentification of members in the
      Anopheles dirus complex, some which are primary malaria vectors in Thailand and
      mainland Southeast Asia, remains problematic because of indistinguishable or
      overlapping morphological characters between sibling species. Moreover, there is
      a need for alternative methods, since the existing molecular techniques in the
      literature are not entirely satisfactory in differentiating all members in the
      An. dirus complex. The nucleotide polymorphisms in the mitochondrial cytochrome c
      oxidase subunit I (COI) sequences were developed to identify the 4 species within
      the An. dirus complex using an allele-specific (AS) multiplex polymerase chain
      reaction (PCR). The identified primers amplified and clearly differentiated the 4
      members of the complex found in Thailand, Anopheles dirus, An. cracens, An.
      scanloni, and An. baimaii with PCR products 428/104, 236, 625, and 428 bp,
      respectively. These results demonstrate that an AS-PCR based on the COI region
      can accurately identify 4 members of An. dirus complex and would be useful as an
      alternative PCR-based method for accurate species identification.

PMID- 29369037
TI  - Correction notice to: Position preference and position change of hiders in the
      game of hide-and-seek.
AB  - Sanderson YB (2018). Position preference and position change of hiders in the
      game of hide-and-seek. Quarterly Journal of Experimental Psychology. 71(5): 1172
      1187. doi: 10.1080/17470218.2017.1322110. The following errors were present in
      the Online First version of this article: Permissions acknowledgements were
      missing from legends to Figures 1, 2 and 3. Figure 2 has been replaced with an
      updated version. The Online First version of the article has been updated with
      these changes and subsequent versions of the article will be corrected.

PMID- 29369038
TI  - Causality and Pleiotropy in the Association Between Bullying Victimization in
      Adolescence and Depressive Episodes in Adulthood.
AB  - Children and adolescents who are victims or perpetrators of bullying
      victimization are at elevated risk for maladjustment problems, concurrently and
      in the long run. Previous studies suggest that this correlation is partly
      explained by genetic influence. However, whether the genetic correlation is
      independent of a causal effect of victimization on maladjustment remains unclear.
      Using data from 2,510 females from the TwinsUK registry, we applied an innovative
      extension of the Cholesky decomposition to investigate to what extent the
      association between victimization in adolescence and self-reported depressive
      episodes in adulthood is caused by shared genetic effects (pleiotropy), and to
      what extent it is due to a phenotypic causal relationship. We find that around
      60% of the association between victimization and self-reported depressive
      episodes is due to a causal effect of victimization on depressive episodes, and
      40% is due to pleiotropic effects. These findings underline the importance of
      integrating genetic information into social science research and demonstrate a
      neat strategy to elucidate causal mechanisms in the absence of experimental
      designs.

PMID- 29369039
TI  - Genetic and Environmental Contributions of Negative Valence Systems to
      Internalizing Pathways.
AB  - The genetic and environmental contributions of negative valence systems (NVS) to
      internalizing pathways study (also referred to as the Adolescent and Young Adult
      Twin Study) was designed to examine varying constructs of the NVS as they relate
      to the development of internalizing disorders from a genetically informed
      perspective. The goal of this study was to evaluate genetic and environmental
      contributions to potential psychiatric endophenotypes that contribute to
      internalizing psychopathology by studying adolescent and young adult twins
      longitudinally over a 2-year period. This report details the sample
      characteristics, study design, and methodology of this study. The first wave of
      data collection (i.e., time 1) is complete; the 2-year follow-up (i.e., time 2)
      is currently underway. A total of 430 twin pairs (N = 860 individual twins; 166
      monozygotic pairs; 57.2% female) and 422 parents or legal guardians participated
      at time 1. Twin participants completed self-report surveys and participated in
      experimental paradigms to assess processes within the NVS. Additionally, parents
      completed surveys to report on themselves and their twin children. Findings from
      this study will help clarify the genetic and environmental influences of the NVS
      and their association with internalizing risk. The goal of this line of research
      is to develop methods for early internalizing disorder risk detection.

PMID- 29369043
TI  - Evaluation of <sup>209</sup>At as a theranostic isotope for <sup>211</sup>At
      radiopharmaceutical development using high-energy SPECT.
AB  - The development of alpha-emitting radiopharmaceuticals using <sup>211</sup>At
      requires quantitative determination of the time-dependent nature of the
      <sup>211</sup>At biodistribution. However, imaging-based methods for acquiring
      this information with <sup>211</sup>At have not found wide-spread use because of
      its low abundance of decay emissions suitable for external detection. In this
      publication we demonstrate the theranostic abilities of the
      <sup>211</sup>At/<sup>209</sup>At isotope pair and present the first-ever
      <sup>209</sup>At SPECT Images. <b>Methods:</b> The VECTor microSPECT/PET/CT
      scanner was used to image <sup>209</sup>At with a collimator suitable for the 511
      keV annihilation photons of PET isotopes. Data from distinct photopeaks of the
      <sup>209</sup>At energy spectrum (195 keV (22.6%), 239 keV (12.4%), 545 keV
      (91.0%), a combined 782/790 keV peak (147%), and <sup>209</sup>Po x-rays
      (139.0%)) were independently evaluated for use in image reconstructions using
      Monte Carlo (GATE) simulations and phantom studies. <sup>209</sup>At-imaging
      <i>in vivo</i> was demonstrated in a healthy mouse injected with 10 MBq of free
      [<sup>209</sup>At]astatide. Image-based measurements of <sup>209</sup>At uptake
      in organs of interest - acquired in 5-minute intervals - were compared to <i>ex
      vivo</i> gamma counter measurements of the same organs. <b>Results:</b> Simulated
      and measured data indicated that - due to the large amount of scatter from high
      energy (>750 keV) gammas - reconstructed images using the x-ray peak outperformed
      those obtained from other peaks in terms of uniformity and spatial resolution,
      determined to be <0.85 mm. <sup>209</sup>At imaging using the x-ray peak revealed
      a biodistribution that matched the known distribution of free astatide, and <i>in
      vivo</i> image-based measurements of <sup>209</sup>At uptake in organs of
      interest matched <i>ex vivo</i> measurements within 10%. <b>Conclusion:</b> We
      have acquired the first <sup> 209</sup>At SPECT images and demonstrated the
      ability of quantitative SPECT imaging with <sup>209</sup>At to accurately
      determine astatine biodistributions with high spatial and temporal resolution.

PMID- 29369044
TI  - A robust deep convolutional neural network for the classification of abnormal
      cardiac rhythm using single lead electrocardiograms of variable length.
AB  - OBJECTIVE: Atrial fibrillation (AF) is a major cause of hospitalization and death
      in the United States. Moreover, as the average age of individuals increases
      around the world, early detection and diagnosis of AF become even more pressing.
      In this paper, we introduce a novel deep learning architecture for the detection
      of normal sinus rhythm, AF, other abnormal rhythms, and noise. APPROACH: We have
      demonstrated through a systematic approach many hyperparameters, input sets, and
      optimization methods that yielded influence in both training time and performance
      accuracy. We have focused on these properties to identify an optimal 13-layer
      convolutional neural network (CNN) model which was trained on 8528 short single
      lead ECG recordings and evaluated on a test dataset of 3658 recordings. MAIN
      RESULTS: The proposed CNN architecture achieved a state-of-the-art performance in
      identifying normal, AF and other rhythms with an average F 1-score of 0.83.
      SIGNIFICANCE: We have presented a robust deep learning-based architecture that
      can identify abnormal cardiac rhythms using short single-lead ECG recordings. The
      proposed architecture is computationally fast and can also be used in real-time
      cardiac arrhythmia detection applications.

PMID- 29369040
TI  - Testing Genetic and Environmental Associations Between Personality Disorders and
      Cocaine Use: A Population-Based Twin Study.
AB  - Until now, data have not been available to elucidate the genetic and
      environmental sources of comorbidity between all 10 DSM-IV personality disorders
      (PDs) and cocaine use. Our aim was to determine which PD traits are linked
      phenotypically and genetically to cocaine use. Cross-sectional data were obtained
      in a face-to-face interview between 1999 and 2004. Subjects were 1,419 twins
      (uage = 28.2 years, range = 19-36) from the Norwegian Institute of Public Health
      Twin Panel, with complete lifetime cocaine use and criteria for all 10 DSM-IV
      PDs. Stepwise multiple and Least Absolute Shrinkage and Selection Operator
      (LASSO) regressions were used to identify PDs related to cocaine use. Twin models
      were fitted to estimate genetic and environmental associations between the PD
      traits and cocaine use. In the multiple regression, antisocial (OR = 4.24, 95% CI
      [2.66, 6.86]) and borderline (OR = 2.19, 95% CI [1.35, 3.57]) PD traits were
      significant predictors of cocaine use. In the LASSO regression, antisocial,
      borderline, and histrionic were significant predictors of cocaine use. Antisocial
      and borderline PD traits each explained 72% and 25% of the total genetic risks in
      cocaine use, respectively. Genetic risks in histrionic PD were not significantly
      related to cocaine use. Importantly, after removing criteria referencing
      substance use, antisocial PD explained 65% of the total genetic variance in
      cocaine use, whereas borderline explained only 4%. Among PD traits, antisocial is
      the strongest correlate of cocaine use, for which the association is driven
      largely by common genetic risks.

PMID- 29369045
TI  - Spine morphology and energetics: how principles from nature apply to robotics.
AB  - Inspired by the locomotive advantages that an articulated spine enables in
      quadrupedal animals, we explore and quantify the energetic effect that an
      articulated spine has in legged robots. We compare two model instances of a
      conceptual planar quadruped: one with a traditional rigid main body and one with
      an articulated main body with an actuated spinal joint. Both models feature four
      distinct legs, series elastic actuation, distributed mass in all body segments,
      and limits on actuator torque and speed. Using optimal control to find the
      energetically optimal joint trajectories, actuator inputs, and footfall timing,
      we examine and compare the positive mechanical work cost of transport of both
      models across multiple gaits and speeds. Our results show that an articulated
      spine increases the maximum possible speed and improves the locomotor economy at
      higher velocities, especially for asymmetrical gaits. The driving factors for
      these improvements are the same mechanistic effects that facilitate asymmetrical
      gaits in nature: improved leg recirculation, elastic energy storage in the spine,
      and enlarged stride lengths.

PMID- 29369046
TI  - Superconductivity in tantalum self-intercalated 4<i>Ha</i>
      Ta<sub>1.03</sub>Se<sub>2</sub>.
AB  - TaSe$_2$ has several different polytypes and abundant physical properties such as
      superconductivity and charge density waves (CDW), which had been investigated in
      the past few decades. However, there is no report on the physical properties of
      4$Ha$&#13; polytype up to now. Here we report the crystal growth and discovery of
      superconductivity in tantalum self-intercalated&#13; 4$Ha$-Ta$_{1.03}$Se$_2$
      single crystal with a superconducting transition onset temperature $T_{?rm c}$
      $?approx$ 2.7 K, which&#13; is the first observation of superconductivity in
      4$Ha$ polytype of TaSe$_2$. A slightly suppressed CDW transition is found around
      106&#13; K. A large $?mu_0H_{?rm c2}/T_{?rm c}$ value of about 4.48 is found when
      magnetic field is applied in the $ab$ plane, which probably results from the
      enhanced spin-orbit coupling(SOC). Special stacking faults are observed, which
      further enhance the anisotropy. Although the density of states at the Fermi level
      is lower than that of other polytypes, $T_{?rm c}$ remains the same, indicating
      the stack mode of 4$Ha$ polytype may be beneficial to superconductivity in
      TaSe$_2$.

PMID- 29369047
TI  - Monte Carlo evaluation of magnetically focused proton beams for radiosurgery.
AB  - The purpose of this project is to investigate the advantages in dose distribution
      and delivery of proton beams focused by a triplet of quadrupole magnets in the
      context of potential radiosurgery treatments. Monte Carlo simulations were
      performed using various configurations of three quadrupole magnets located
      immediately upstream of a water phantom. Magnet parameters were selected to match
      what can be commercially manufactured as assemblies of rare-earth permanent
      magnetic materials. Focused unmodulated proton beams with a range of ~10 cm in
      water were target matched with passive collimated beams (the current beam
      delivery method for proton radiosurgery) and properties of transverse dose, depth
      dose and volumetric dose distributions were compared. Magnetically focused beams
      delivered beam spots of low eccentricity to Bragg peak depth with full widths at
      the 90% reference dose contour from ~2.5 to 5 mm. When focused initial beam
      diameters were larger than matching unfocused beams (10 of 11 cases) the focused
      beams showed 16%-83% larger peak-to-entrance dose ratios and 1.3 to 3.4-fold
      increases in dose delivery efficiency. Peak-to-entrance and efficiency benefits
      tended to increase with larger magnet gradients and larger initial diameter
      focused beams. Finally, it was observed that focusing tended to shift dose in the
      water phantom volume from the 80%-20% dose range to below 20% of reference dose,
      compared to unfocused beams. We conclude that focusing proton beams immediately
      upstream from tissue entry using permanent magnet assemblies can produce beams
      with larger peak-to-entrance dose ratios and increased dose delivery
      efficiencies. Such beams could potentially be used in the clinic to irradiate
      small-field radiosurgical targets with fewer beams, lower entrance dose and
      shorter treatment times.

PMID- 29369048
TI  - Reaction paths of alane dissociation on the Si(0 0 1) surface.
AB  - Building on our earlier study, we examine the kinetic barriers to decomposition
      of alane, AlH3, on the Si(0 0 1) surface, using the nudged elastic band approach
      within density functional theory. We find that the initial decomposition to AlH
      with two H atoms on the surface proceeds without a significant barrier. There are
      several pathways available to lose the final hydrogen, though these present
      barriers of up to 1 eV. Incorporation is more challenging, with the initial
      structures less stable in several cases than the starting structures, just as was
      found for phosphorus. We identify a stable route for Al incorporation following
      selective surface hydrogen desorption (e.g. by scanning tunneling microscope
      tip). The overall process parallels PH3, and indicates that atomically precise
      acceptor doping should be possible.

PMID- 29369049
TI  - Comparison of <i>k</i><sub>Q</sub> factors measured with a water calorimeter in
      flattening filter free (FFF) and conventional flattening filter (cFF) photon
      beams.
AB  - Recently flattening filter free (FFF) beams became available for application in
      modern radiotherapy. There are several advantages of FFF beams over conventional
      flattening filtered (cFF) beams, however differences in beam spectra at the point
      of interest in a phantom potentially affect the ion chamber response. Beams are
      also non-uniform over the length of a typical reference ion chamber and
      recombination is usually larger. Despite several studies describing FFF beam
      characteristics, only a limited number of studies investigated their effect on
      <i>k</i><sub>Q</sub> factors. Some of those studies predicted significant
      discrepancies in <i>k</i><sub>Q</sub> factors (0.4 % up to 1.0 %) if
      TPR<sub>20,10</sub> based codes of practice (CoPs) would be used. This study
      addresses the question to which extent <i>k</i><sub>Q</sub> factors, based on a
      TPR<sub>20,10</sub> CoP, can be applied in clinical reference dosimetry. It is
      the first study that compares <i>k</i><sub>Q</sub> factors measured directly with
      an absorbed dose to water primary standard in FFF-cFF pairs of clinical photon
      beams. This was done with a transportable water calorimeter described elsewhere.
      The measurements corrected for recombination and beam radial non-uniformity were
      performed in FFF-cFF beam pairs at 6 MV and 10 MV of an Elekta Versa HD for a
      selection of three different Farmer-type ion chambers (8 serial numbers). The
      ratio of measured <i>k</i><sub>Q</sub> factors of the FFF-cFF beam pairs were
      compared with the TPR<sub>20,10</sub> CoPs of the NCS and IAEA and the
      <i>%dd</i>(10)<sub>x</sub> CoP of the AAPM. For the TPR<sub>20,10</sub> based
      CoPs differences less than 0.23 % were found in <i>k</i><sub>Q</sub> factors
      between the corresponding FFF-cFF beams with standard uncertainties smaller than
      0.35 %, while for the <i>%dd</i>(10)<sub>x</sub> these differences were smaller
      than 0.46 % and within the expanded uncertainty of the measurements. Based on the
      measurements made with the equipment described in this study the authors conclude
      that the <i>k</i><sub>Q</sub> factors provided by the NCS-18 and IAEA TRS-398
      codes of practice can be applied for flattening filter free beams without
      additional correction. However, existing codes of practice cannot be applied
      ignoring the significant volume averaging effect of the FFF beams over the ion
      chamber cavity. For this a corresponding volume averaging correction must be
      applied.

PMID- 29369050
TI  - Endocardial center motion for quantification of left ventricular discoordination
      in heart failure using cine MRI.
AB  - OBJECTIVE: To compare a novel cardiovascular magnetic resonance technique for the
      assessment of left ventricular (LV) mechanical discoordination by characterizing
      the endocardial center motion (ECM) in short-axis cine MRI in healthy volunteers
      and heart failure patients with left bundle branch block (HF-LBBB). APPROACH: To
      evaluate ECM analysis as mechanical discoordination measure, we retrospectively
      compared spatial and temporal features of the ECM between a group of healthy
      volunteers (n  =  14) and conduction defect patients (HF-LBBB, n  =  31). We
      tracked the center of the endocardial borders on short-axis view MRI cine loops
      during the cardiac cycle. From the ECM trajectory we calculated the overall
      traveled distance, the enclosed area, the eccentricity of the trajectory, and the
      maximum traveled distance. The ECM can be visualized in spatial coordinates as
      well as by its temporal behavior. We evaluated the classification performance of
      these measures for LBBB detection. We also quantified the coherence of the ECM on
      the longitudinal direction by considering the variability of the ECM measures
      between different short-axis slices. MAIN RESULTS: Patients with LBBB showed
      significantly higher traveled distance (p  <  0.0001), enclosed area (p  < 
      0.002), eccentricity (p  <  0.02), and peak displacement (p  <  0.02) of the
      endocardial center. Patients with positive late gadolinium enhancement showed a
      higher variability of ECM measures across different slices (p  <  0.05).
      SIGNIFICANCE: ECM analysis is feasible and it allows the assessment of left
      ventricular mechanical discoordination. Differences in ECM measures permit one to
      distinguish between LBBB and healthy volunteers.

PMID- 29369051
TI  - First Description of QTc Prolongation Associated With Clonazepam Overdose in a
      Pediatric Patient.

PMID- 29369052
TI  - Iodine-Associated Sialadenitis: An Inflammatory Condition.

PMID- 29369053
TI  - Acute Phase Predictors of 6-Month Functional Outcome in Italian Stroke Patients
      Eligible for In-Hospital Rehabilitation.
AB  - PURPOSE: The aim of the study was to assess early poststroke prognostic factors
      in patients admitted for postacute phase rehabilitation. METHODS: A 1-yr
      multicenter prospective project was conducted in four Italian regions on 352
      patients who were hospitalized after a first stroke and were eligible for
      postacute rehabilitation. Clinical data were collected in the stroke or acute
      care units (acute phase), then in rehabilitation units (postacute phase), and,
      subsequently, after a 6-mo poststroke period (follow-up). Clinical outcome
      measures were represented using the Barthel Index and the modified Rankin Scale.
      Univariate and multivariate analyses were performed to identify the most
      important prognostic index. RESULTS: Modified Rankin Scale score, minor
      neurologic impairment, and early out-of-bed mobilization (within 2 days after the
      stroke) proved to be important factors related to a better recovery according to
      Barthel Index (power of prediction = 37%). Similarly, age, premorbid modified
      Rankin Scale score, and early out-of-bed mobilization were seen to be significant
      factors in achieving better overall participation and activity according to the
      modified Rankin Scale (power of prediction = 48%). Barthel Index at admission and
      certain co-morbidities were also significant prognostic factors correlated with a
      better outcome. CONCLUSIONS: According to the Barthel Index and modified Rankin
      Scale, early mobilization is an early predictor of favorable outcome. TO CLAIM
      CME CREDITS: Complete the self-assessment activity and evaluation online at
      http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this
      article, the reader should be able to: (1) Incorporate prognostic factors of good
      clinical outcomes after stroke in developing treatment plans for patients
      admitted to rehabilitation; (2) Identify acute phase indicators associated with
      favorable 6-mo outcome after stroke; and (3) Recognize the cut-off for early
      mobilization linked to better outcome in stroke survivors admitted to
      rehabilitation. LEVEL: Advanced ACCREDITATION: The Association of Academic
      Physiatrists is accredited by the Accreditation Council for Continuing Medical
      Education to provide continuing medical education for physicians.The Association
      of Academic Physiatrists designates this Journal-based CME activity for a maximum
      of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit
      commensurate with the extent of their participation in the activity.

PMID- 29369054
TI  - Lack of paclitaxel effects on intracranial self-stimulation in male and female
      rats: comparison to mechanical sensitivity.
AB  - Paclitaxel is a cancer chemotherapy with adverse effects that include peripheral
      neuropathy, neuropathic pain, and depression of behavior and mood. In rodents,
      hypersensitive paw-withdrawal reflexes from mechanical stimuli serve as one
      common measure of paclitaxel-induced pain-related behavior. This study tested the
      hypothesis that paclitaxel would also depress rates of positively reinforced
      operant responding as a measure of pain-related behavioral depression. Male and
      female Sprague-Dawley rats were equipped with electrodes targeting the medial
      forebrain bundle, trained to lever press for electrical brain stimulation in an
      assay of intracranial self-stimulation (ICSS), and treated with four injections
      of varying paclitaxel doses (0.67, 2.0, or 6.0 mg/kg/injection*4 injections on
      alternate days). Mechanical sensitivity, body weight, and ICSS were evaluated
      before, during, and for 3 weeks after paclitaxel treatment. Paclitaxel doses
      sufficient to produce mechanical hypersensitivity did not reliably depress ICSS
      in male or female rats. Moreover, the degree of behavioral suppression in
      individual rats did not correlate with mechanical sensitivity. Paclitaxel
      treatment regimens commonly used to model chemotherapy-induced neuropathic pain
      in rats are not sufficient to depress ICSS.

PMID- 29369055
TI  - Corticosteroids in Pediatric Septic Shock Are Not Helpful.

PMID- 29369056
TI  - Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A
      Murine Trial.
AB  - OBJECTIVES: Sepsis, the acute organ dysfunction caused by a dysregulated host
      response to infection, poses a serious public health burden. Current management
      includes early detection, initiation of antibiotics and fluids, and source
      control as necessary. Although observational data suggest that delays of even a
      few hours in the initiation of antibiotics or IV fluids is associated with
      survival, these findings are controversial. There are no randomized data in
      humans, and prior animal studies studied time from experimental manipulation, not
      from the onset of clinical features of sepsis. Using a recently developed murine
      cecal ligation and puncture model that precisely monitors physiologic
      deterioration, we hypothesize that incremental hourly delays in the first dose of
      antibiotics, in the first bolus of fluid resuscitation, or a combination of the
      two at a clinically relevant point of physiologic deterioration during
      polymicrobial sepsis will shorten survival. DESIGN: Randomized laboratory animal
      experimental trial. SETTING: University basic science laboratory. SUBJECTS: Male
      C57BL/6J, female C57BL/6J, aged (40-50 wk old) male C57BL/6J, and BALB/C mice.
      INTERVENTIONS: Mice (n = 200) underwent biotelemetry-enhanced cecal ligation and
      puncture and were randomized after meeting validated criteria for acute
      physiologic deterioration. Treatment groups consisted of a single dose of
      imipenem/cilastatin, a single bolus of 30 mL/kg fluid resuscitation, or a
      combination of the two. Mice were allocated to receive treatment at the time of
      meeting deterioration criteria, after a 2-hour delay or after a 4-hour delay.
      MEASUREMENTS AND MAIN RESULTS: Hourly delays in the initiation of antibiotic
      therapy led to progressively shortened survival in our model (p < 0.001). The
      addition of fluid resuscitation was unable to rescue animals, which received
      treatment 4 hours after meeting enrollment criteria. Systemic inflammation was
      increased, and host physiology was increasingly deranged with hourly delays to
      antibiotics. CONCLUSIONS: We conclude that antibiotic therapy is highly time
      sensitive, and efforts should be made to deliver this critical therapy as early
      as possible in sepsis, perhaps extending into the first point of medical contact
      outside the hospital.

PMID- 29369058
TI  - Delayed Presentation of Compartment Syndrome of the Thigh in a Previously
      Undiagnosed Factor VII-Deficient High School Football Athlete: A Case Report.
AB  - CASE: We describe a case of delayed presentation of compartment syndrome in the
      anterior aspect of the thigh in a high school athlete. The patient had sustained
      a blow to the thigh 8 days prior to presentation, and had continued to practice
      football in the setting of undiagnosed coagulopathy. He presented with severe
      thigh pain and the inability to contract the thigh muscles. CONCLUSION: A high
      index of suspicion for compartment syndrome is indicated for patients with
      disproportionate pain, especially in the setting of relatively minor trauma.
      Underlying coagulopathy should be investigated in patients with compartment
      syndrome because there is a high incidence of bleeding disorders in this
      population.

PMID- 29369057
TI  - Clinical Epidemiology of Adults With Moderate Traumatic Brain Injury.
AB  - OBJECTIVES: To characterize admission patterns, treatments, and outcomes among
      patients with moderate traumatic brain injury. DESIGN: Retrospective cohort
      study. SETTING: National Trauma Data Bank. PATIENTS: Adults (age > 18 yr) with
      moderate traumatic brain injury (International Classification of Diseases, Ninth
      revision codes and admission Glasgow Coma Scale score of 9-13) in the National
      Trauma Data Bank between 2007 and 2014. INTERVENTIONS: None. MEASUREMENT AND MAIN
      RESULTS: Demographics, mechanism of injury, hospital course, and facility
      characteristics were examined. Admission characteristics associated with
      discharge outcomes were analyzed using multivariable Poisson regression models.
      Of 114,066 patients, most were white (62%), male (69%), and had median admission
      Glasgow Coma Scale score of 12 (interquartile range, 10-13). Seventy-seven
      percent had isolated traumatic brain injury. Concussion, which accounted for 25%
      of moderate traumatic brain injury, was the most frequent traumatic brain injury
      diagnosis. Fourteen percent received mechanical ventilation, and 66% were
      admitted to ICU. Over 50% received care at a community hospital. Seven percent
      died, and 32% had a poor outcome, including those with Glasgow Coma Scale score
      of 13. Compared with patients 18-44 years, patients 45-64 years were twice as
      likely (adjusted relative risk, 1.97; 95% CI, 1.92-2.02) and patients over 80
      years were five times as likely (adjusted relative risk, 4.66; 95% CI, 4.55-4.76)
      to have a poor outcome. Patients with a poor discharge outcome were more likely
      to have had hypotension at admission (adjusted relative risk, 1.10; 95% CI, 1.06
      1.14), lower admission Glasgow Coma Scale (adjusted relative risk, 1.37; 95% CI,
      1.34-1.40), higher Injury Severity Score (adjusted relative risk, 2.97; 95% CI,
      2.86-3.09), and polytrauma (adjusted relative risk, 1.05; 95% CI, 1.02-1.07),
      compared with those without poor discharge outcomes. CONCLUSIONS: Many patients
      with moderate traumatic brain injury deteriorate, require neurocritical care, and
      experience poor outcomes. Optimization of care and outcomes for this vulnerable
      group of patients are urgently needed.

PMID- 29369059
TI  - Use of an Ultrasonic Bone Curet for the Extraction of a Cervical Artificial Disc:
      A Novel Application: A Case Report.
AB  - CASE: Eighteen months after implantation of a C6-C7 cervical artificial disc
      (ProDisc-C; DePuy Synthes), a 44-year-old woman presented with right-sided C7
      radiculopathy. Imaging revealed posterior subsidence of the prosthesis, with C7
      foraminal stenosis. An ultrasonic curet was used to safely and effectively
      extract the prosthesis without neurologic complication; safe access for the
      insertion of an intervertebral cage was facilitated. CONCLUSION: The ultrasonic
      curet was a safe and effective adjunct for revision artificial cervical disc
      replacement surgery; this technique may help to reduce potential injury to neural
      structures in a procedure with a traditionally high complication rate.

PMID- 29369060
TI  - Tendon Transfers to Restore Ankle Dorsiflexion After Anterior Compartment
      Myonecrosis: A Case Report.
AB  - CASE: A 47-year-old Caucasian woman spontaneously developed an isolated anterior
      compartment pressure of >100 mm Hg in the left leg. Despite fasciotomies, the
      musculature was nonviable and required debridement. Following Achilles tendon
      lengthening, a posterior tibial tendon (PTT) to anterior tibial tendon (ATT)
      transfer was supplemented with a flexor digitorum longus tendon transfer to the
      remaining PTT in order to prevent a flatfoot deformity while restoring active
      dorsiflexion. CONCLUSION: Preservation of the tendinous portion of the ATT during
      debridement allowed for transfer of the PTT to the ATT using a modified
      Pulvertaft transfer. This technique allowed early ambulation and restoration of
      active dorsiflexion, obviating the ongoing use of an ankle-foot orthosis.

PMID- 29369061
TI  - Reduced H3K27me3 Expression is Common in Nodular Melanomas of Childhood
      Associated With Congenital Melanocytic Nevi But Not in Proliferative Nodules.

PMID- 29369062
TI  - Simulation-based Assessment to Reliably Identify Key Resident Performance
      Attributes.
AB  - BACKGROUND: Obtaining reliable and valid information on resident performance is
      critical to patient safety and training program improvement. The goals were to
      characterize important anesthesia resident performance gaps that are not
      typically evaluated, and to further validate scores from a multiscenario
      simulation-based assessment. METHODS: Seven high-fidelity scenarios reflecting
      core anesthesiology skills were administered to 51 first-year residents (CA-1s)
      and 16 third-year residents (CA-3s) from three residency programs. Twenty trained
      attending anesthesiologists rated resident performances using a seven-point
      behaviorally anchored rating scale for five domains: (1) formulate a clear plan,
      (2) modify the plan under changing conditions, (3) communicate effectively, (4)
      identify performance improvement opportunities, and (5) recognize limits. A
      second rater assessed 10% of encounters. Scores and variances for each domain,
      each scenario, and the total were compared. Low domain ratings (1, 2) were
      examined in detail. RESULTS: Interrater agreement was 0.76; reliability of the
      seven-scenario assessment was r = 0.70. CA-3s had a significantly higher average
      total score (4.9 +/- 1.1 vs. 4.6 +/- 1.1, P = 0.01, effect size = 0.33). CA-3s
      significantly outscored CA-1s for five of seven scenarios and domains 1, 2, and
      3. CA-1s had a significantly higher proportion of worrisome ratings than CA-3s
      (chi-square = 24.1, P < 0.01, effect size = 1.50). Ninety-eight percent of
      residents rated the simulations more educational than an average day in the
      operating room. CONCLUSIONS: Sensitivity of the assessment to CA-1 versus CA-3
      performance differences for most scenarios and domains supports validity. No
      differences, by experience level, were detected for two domains associated with
      reflective practice. Smaller score variances for CA-3s likely reflect a training
      effect; however, worrisome performance scores for both CA-1s and CA-3s suggest
      room for improvement.

PMID- 29369063
TI  - Long-term outcome following decompressive craniectomy: an inconvenient truth?
AB  - PURPOSE OF REVIEW: There is little doubt that decompressive craniectomy can
      reduce mortality following malignant middle cerebral infarction or severe
      traumatic brain injury. However, the concern has always been that the reduction
      in mortality comes at the cost of an increase in the number of survivors with
      severe neurological disability. RECENT FINDINGS: There has been a number of large
      multicentre randomized trials investigating surgical efficacy of the procedure.
      These trials have clearly demonstrated a survival benefit in those patients
      randomized to surgical decompression. However, it is only possible to demonstrate
      an improvement in outcome if the definition of favourable is changed such that it
      includes patients with either a modified Rankin score of 4 or upper severe
      disability. Without this recategorization, the results of these trials have
      confirmed the 'Inconvenient truth' that surgery reduces mortality at the expense
      of survival with severe disability. SUMMARY: Given these results, the time may
      have come for a nuanced examination of the value society places on an individual
      life, and the acceptability or otherwise of performing a procedure that converts
      death into survival with severe disability.

PMID- 29369064
TI  - Neuro-ICU patient disposition: optimal venue for acute needs.
AB  - PURPOSE OF REVIEW: This article revises the recent evidence on ICU admission
      criteria for acute neurological patients [traumatic brain injury (TBI) patients,
      postoperative neurosurgical procedures and stroke]. RECENT FINDINGS: The
      appropriate utilization of ICU beds is essential, but it is complex and a
      challenge to attain. To date there are no widely accepted international
      guidelines for managing these acute brain-injured patients (stroke, TBI,
      postneurosurgery) in the ICU. The criteria for ICU admission after neurological
      acute injury, high-dependency unit or a specialized neurosurgical ward vary from
      institution to institution depending on local structures and characteristics of
      the available resources. Better evidence to standardize the treatment and the
      degree of monitoring is needed during neurological acute injury. It is highly
      recommended to implement clinical vigilance in these patients regardless of their
      destination (ICU, stroke unit or ward). SUMMARY: Currently evidence do not allow
      to define standardized protocol to guide ICU admission for acute neurological
      patients (TBI patients, postoperative neurosurgical procedures and stroke).

PMID- 29369065
TI  - Spirituality at the end of life.
AB  - PURPOSE OF REVIEW: There is increasing emphasis on medical care of the whole
      patient. This holistic approach encompasses supporting the spiritual or religious
      needs of the patient. Particularly at the end of life, spiritual concerns may
      come to the fore as patients recognize and accept their impending death.
      Physicians may also recognize this spiritual distress but may not be clear on how
      to provide spiritual support. RECENT FINDINGS: Tools to screen for spiritual
      concerns are available for physicians to use. Some physicians wish to go further,
      supporting patients at the end of life in their spiritual quest. Other physicians
      express concern about causing more distress to patients in a time of significant
      need. Descriptions of educational tools, as well as the difference between
      spiritual generalists and spiritual specialists have emerged. Integration of
      chaplains into the medical team caring for patients at the end of life will also
      enhance care of the whole patient. SUMMARY: The increasing emphasis on whole
      patient care is leading to increasing focus on spiritual concerns of patients.
      Although not every patient has an interest in spiritual conversation, most do and
      medical teams will need to become more educated about appropriate spiritual
      engagement.

PMID- 29369068
TI  - Applications of near infrared spectroscopy in the neonate.
AB  - PURPOSE OF REVIEW: There has been a significant increase in the utilization of
      NIRS in neonatal care over the last few years, with some centers now routinely
      utilizing this monitoring technique for direct intervention at the bedside. In
      this review, we provide a summary of the most up-to-date evidence on near
      infrared spectroscopy utilization, with particular emphasis on measurement of
      cerebral oxygenation in preterm infants. RECENT FINDINGS: There have been
      significant advances in the technology, leading to an increase in the number of
      available devices and in the use of this monitoring tool to reduce cerebral
      injury in preterm infants. The role of NIRS in assessing cerebral autoregulation
      in preterm and term infants, in evaluating somatic oxygenation, and in the
      management of newborns with hypoxic ischaemic encephalopathy is discussed.
      SUMMARY: Two recent pilot randomized controlled trials highlight the potential of
      cerebral oxygenation monitoring to direct management in the delivery room and the
      neonatal intensive care unit. However, we urge caution against routine use and
      await the results of further studies in this area before considering this type of
      monitoring as standard of care.

PMID- 29369066
TI  - Transfusion practices in traumatic brain injury.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize the recent studies
      looking at the effects of anemia and red blood cell transfusion in critically-ill
      patients with traumatic brain injury (TBI), describe the transfusion practice
      variations observed worldwide, and outline the ongoing trials evaluating
      restrictive versus liberal transfusion strategies for TBI. RECENT FINDINGS:
      Anemia is common among critically-ill patients with TBI, it is also thought to
      exacerbate secondary brain injury, and is associated with an increased risk of
      poor outcome. Conversely, allogenic red blood cell transfusion carries its own
      risks and complications, and has been associated with worse outcomes. Globally,
      there are large reported differences in the hemoglobin threshold used for
      transfusion after TBI. Observational studies have shown differential results for
      improvements in cerebral oxygenation and metabolism after red blood cell
      transfusion in TBI. SUMMARY: Currently, there is insufficient evidence to make
      strong recommendations regarding which hemoglobin threshold to use as a
      transfusion trigger in critically-ill patients with TBI. There is also
      uncertainty whether the restrictive transfusion strategy used in general critical
      care can be extrapolated to acutely brain injured patients. Ultimately, the
      consequences of anemia-induced cerebral injury need to be weighed up against the
      risks and complications associated with red blood cell transfusion.

PMID- 29369069
TI  - Innovative Practice in Advancement of Academic Nurse Educator Careers: Developing
      Scholarship From Program Grants.
AB  - We describe an innovative practice in advancing careers of academic nurse
      educators: demonstrating scholarly productivity from program grants. Scholarly
      productivity is often narrowly defined, especially in research-intensive
      institutions. The expectation may be a career trajectory based on the traditional
      scholarship of discovery. However, nurse educators, especially at the associate
      and full professor ranks, are often involved in leadership activities that
      include writing and managing program grants. We encourage the academy to value
      and support the development of program grants that include significant scholarly
      components, and we offer exemplars of associate and full professor scholarship
      derived from these projects.

PMID- 29369067
TI  - Evidence establishing a link between prenatal and early-life stress and asthma
      development.
AB  - PURPOSE OF REVIEW: The objective of this review is to provide an update on our
      evolving understanding of the effects of stress in pregnancy and during early
      development on the onset of asthma-related phenotypes across childhood,
      adolescence, and into early adulthood. RECENT FINDINGS: Accumulating evidence
      over the past 2 decades has established that prenatal and early-life
      psychological stress and stress correlates (e.g., maternal anxiety or depression)
      increase the risk for childhood respiratory disorders. Recent systematic reviews
      and meta-analyses including numerous prospective epidemiological and case-control
      studies substantiate a significant effect of prenatal stress and stress in early
      childhood on the development of wheeze, asthma, and other atopic-related
      disorders (eczema and allergic rhinitis), with many studies showing an exposure
      response relationship. Offspring of both sexes are susceptible to perinatal
      stress, but effects differ. The impact of stress on child wheeze/asthma can also
      be modified by exposure timing. Moreover, coexposure to prenatal stress can
      enhance the effect of chemical stressors, such as prenatal traffic-related air
      pollution, on childhood respiratory disease risk. Understanding complex
      interactions among exposure dose, timing, child sex, and concurrent environmental
      exposures promises to more fully characterize stress effects and identify
      susceptible subgroups. Although the link between perinatal stress and childhood
      asthma-related phenotypes is now well established, pathways by which stress
      predisposes children to chronic respiratory disorders are not as well delineated.
      Mechanisms central to the pathophysiology of wheeze/asthma and lung growth and
      development overlap and involve a cascade of events that include disrupted
      immune, neuroendocrine, and autonomic function as well as oxidative stress.
      Altered homeostatic functioning of these integrated systems during development
      can enhance vulnerability to asthma and altered lung development. SUMMARY:
      Mechanistic studies that more comprehensively assess biomarkers reflecting
      alterations across interrelated stress response systems and associated regulatory
      processes, in both pregnant women and young children, could be highly
      informative. Leveraging high-throughput systems-wide technologies to include
      epigenomics (e.g., DNA methylation, microRNAs), transcriptomics, and microbiomics
      as well as integrated multiomics are needed to advance this field of science.
      Understanding stress-induced physiological changes occurring during vulnerable
      life periods that contribute to chronic respiratory disease risk could lead to
      the development of preventive strategies and novel therapeutic interventions.

PMID- 29369070
TI  - An Examination of How Gender May Relate to Communication Styles of Introversion
      and Extroversion in Nursing Students.
AB  - This research brief explores the relationship between introversion and
      extroversion communication styles and gender in nursing students. Although
      communication is integral for delivering safe patient care, teaching about
      individual communication styles is rare in nursing curricula. The Myers-Briggs
      Type Indicator (MBTI) was administered to 47 nursing students. Chi-square was
      used to analyze relationships between introversion/extroversion and gender. The
      data reported no significance relationships between introverts and extroverts and
      gender. The findings contribute to nursing education by bringing awareness of
      communication preference tools like the MBTI.

PMID- 29369071
TI  - Using System Inflammatory Response Syndrome as an Easy-to-Implement, Sustainable,
      and Automated Tool for All-Cause Deterioration Among Medical Inpatients.
AB  - OBJECTIVES: Clinical deterioration detection among adult inpatients is known to
      be suboptimal, and many electronic health record tools have been developed to
      help identify these patients. Many of these tools are focused on sepsis spectrum
      disorders, but the evolution of the definition of sepsis is moving toward
      increased specificity, which may make automated detection of clinical
      deterioration from nonsepsis-related conditions less likely. The objectives of
      this study were to develop and to examine the use of a low-cost, highly
      sustainable deterioration detection tool based on systemic inflammatory response
      syndrome (SIRS) criteria. METHODS: Using existing resources, a SIRS-based
      electronic health record monitoring and intervention tool was developed with a
      focus on ease of implementation and high sustainability. This tool was used to
      monitor 15,739 adult inpatients in real time during their admission. RESULTS: The
      SIRS-based tool, created with focus on ease of implementation and high
      sustainability, identified patients with higher risk of clinical deterioration.
      The project was rapidly deployed for a 4-month period at a 900-bed campus of an
      academic medical center with minimal additional resources required. CONCLUSIONS:
      Whereas the definition of sepsis moves away from SIRS, SIRS-based criteria may
      still have clinical benefit as an easy-to-automate detection tool for all-cause
      clinical deterioration among medical inpatients.

PMID- 29369072
TI  - Patient-Reported Dental Safety Events: A South African Perspective.
AB  - OBJECTIVES: In recent years, there has been an increase in research studies
      highlighting patients' experiences of adverse events (AEs) as well as the role of
      patients in promoting safety. The primary goal of the study was to assess the
      prevalence of dental AEs (DAEs) among dental patients in South Africa and its
      associated factors. The integration of the patient perspective into dental
      patient safety research will enhance our collective understanding of DAEs.
      METHODS: We conducted a cross-sectional study of adult patients at a large dental
      academic institution in South Africa from May to June 2015, evaluating their
      previous experiences of DAEs at any dental clinic in South Africa. Descriptive
      statistics and bivariate and multivariate analyses were performed to identify the
      factors associated with an increased likelihood of experiencing a DAE. RESULTS: A
      total of 440 questionnaires were returned during the 6-week study period
      (response rate = 97.8%). Overall, 45.5% of participants reported experiencing one
      or more DAEs. Two hundred participants reported a total of 717 DAEs giving us a
      lifetime prevalence of 1.6 DAEs per respondent. Our results suggest that
      respondents who were younger (18-24 y), from high-income families (>R150,000 or
      US $9200), dissatisfied with their last dental visit and oral health had an
      increased likelihood of reporting a previous experience of a DAE. CONCLUSIONS:
      This study provides an insight into the nature of information that can be gleaned
      from dental patients regarding safety and helps lay the foundation for patient
      involvement in patient safety reporting.

PMID- 29369073
TI  - Effects of a Kundalini Yoga Program on Elementary and Middle School Students'
      Stress, Affect, and Resilience.
AB  - OBJECTIVE: The Your Own Greatness Affirmed (YOGA) for Youth program delivers yoga
      to urban inner-city schools with the goal of providing practical benefits that
      support underserved children at high risk of behavioral and emotional problems. A
      10-week YOGA for Youth program delivered 1 to 2 times per week was implemented in
      3 schools in urban neighborhoods to examine the effect of the program on student
      stress, affect, and resilience. METHODS: Thirty children were administered the
      Perceived Stress Scale, the Positive and Negative Affect Schedule, and the
      Resilience Scale before and after the yoga program. After the program, informal
      qualitative interviews were conducted with school teachers, yoga teachers, and
      students to determine the overall impact of the yoga program. RESULTS: The
      quantitative results of this study indicated that the yoga program significantly
      improved students stress (p < 0.05), positive affect (p < 0.05), and resilience
      (p < 0.001). The qualitative results indicated that students, school teachers,
      and yoga teachers all found the program to be beneficial for students' well
      being. CONCLUSION: Taken together, these data suggest that the YOGA for Youth
      program may provide students in low-income urban schools with behavioral skills
      that will protect against risk factors associated with the development of
      behavioral and emotional problems.

PMID- 29369074
TI  - Concomitant Transcranial Direct Current Stimulation With Ultrabrief
      Electroconvulsive Therapy: A 2-Week Double-Blind Randomized Sham-Controlled
      Trial.
AB  - OBJECTIVE: The feasibility and effectiveness of concomitant use of transcranial
      direct current stimulation (tDCS) with electroconvulsive therapy (ECT) has not
      been investigated. The study principally aimed at determining whether tDCS when
      combined with ECT improved the speed of antidepressant response. Secondarily, the
      ease of generation of seizures during electroconvulsive therapy and cognitive
      outcomes were investigated. METHODS: Consecutive patients referred for ECT to
      treat major depression were randomized to tDCS with dorsolateral prefrontal
      electrode placements (n = 8) or sham (n = 8) used daily and just before thrice
      weekly, 6 times threshold, right unilateral ultrabrief (0.3 ms) pulse width ECT.
      Change of depression severity was determined using the Montgomery Asberg
      Depression Rating Scale along with cognitive assessments using Montreal Cognitive
      Assessment and visual memory testing at weeks 1 and 2, which were compared with
      baseline. RESULTS: Change of depression severity from baseline was similar in
      tDCS and ECT compared with sham tDCS and ECT at week1 (mean [standard deviation
      {SD}] = 16.00 [6.78]; 13.75 [7.83]; P = 0.89) and at week 2 (mean [SD] = 23.00
      [4.96]; 19.75 [9.85], P = 0.08). No between-group differences were obtained in
      the cognitive tests at weeks 1 and 2. Combining tDCS with ECT resulted in higher
      restimulation: 62.5% requiring 3 stimulations to achieve threshold in contrast to
      12.5% with sham tDCS and ECT (P = 0.04). The mean suprathreshold dose was higher
      in the tDCS and ECT group compared with sham tDCS and ECT: mean [SD] = 144.0
      [43.54] and mean [SD] = 122.4 [20.36], P = 0.04, respectively. CONCLUSIONS:
      Concomitant use of tDCS with ultrabrief right unilateral ECT is feasible and safe
      albeit with higher rates of restimulation when tDCS was combined with ECT.
      However, there were no statistically significant differences in the speed of
      antidepressant response or cognitive outcomes at weeks 1 and 2 after the
      commencement of treatments.

PMID- 29369075
TI  - Reporting guideline and clinical trial registration requirements in
      gastroenterology and hepatology journals.
AB  - AIM: The objective of this study was to evaluate the current recommendations and
      requirements of gastroenterology and hepatology journals concerning reporting
      guidelines and clinical trial registration. Current research on the topic is
      sparse and in need of further research in both clinical trial registration and
      guideline adherence. METHODS: The authors performed a review of journal protocols
      and 'Instructions for Authors' regarding guideline adherence and trial
      registration requirements within 30 gastroenterology and hepatology journals. We
      searched the Expanded Science Citation Index of the 2015 Journal Citation Reports
      to determine if each journal required, recommended, or made no mention of 17
      guidelines and clinical trial registration. RESULTS: A majority (23/30; 76.7%) of
      the journals either required or recommended reporting guideline usage, whereas
      the remainder (7/30; 23.3%) had no such policy. In addition, 14 (14/30; 46.7%)
      require or recommend trial registration. Journals with a higher impact factor
      were associated with greater reporting guideline adherence (rpb = 0.43, P <
      0.05). There was not a significant relationship between journal impact factor and
      trial registration requirements (rpb = 0.16, P > 0.05). Consolidated Standards of
      Reporting Trials was the most often required guideline (9/30; 30%), whereas
      Animal Research: Reporting of In Vivo Experiments and Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses were tied for second most often required
      (6/30 each; 20% each). Clinical trial registration was most common via
      ClinicalTrials.gov (9/30; 30%). CONCLUSION: A majority of gastroenterology or
      hepatology journals either require or recommend reporting guideline usage, but
      just less than one-half of the journals did the same for trial registration.

PMID- 29369077
TI  - Is There an Optimum Duration of Fluid Bolus in Pediatric Septic Shock? A Critical
      Appraisal of "Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour
      of Resuscitation in Children With Septic Shock: A Randomized Controlled Trial" by
      Sankar et al (Pediatr Crit Care Med 2017; 18:e435-e445).
AB  - OBJECTIVES: To review the findings and discuss the implications of a longer
      duration for fluid boluses in the resuscitation of children with septic shock.
      DATA SOURCES: We performed a PubMed.gov search using the criteria "Fluid Bolus"
      and "Children" and "Septic Shock," which yielded 29 references. STUDY SELECTION:
      One trial compared different durations of fluid boluses in pediatric septic shock
      and was therefore selected for critical appraisal. (Sankar J, Ismail J, Sankar
      MJ, et al: Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour of
      Resuscitation in Children with Septic Shock: A Randomized Controlled Trial.
      Pediatr Crit Care Med 2017; 18:e435-e445.) DATA EXTRACTION:: This trial compared
      the effectiveness of 20 mL/kg fluid boluses, in children with septic shock, given
      over 15-20 versus 5-10 minutes in terms of need for invasive ventilation and/or
      increase in oxygenation index by 5 from baseline at 6 and 24 hours post initial
      fluid resuscitation. The relative risk of the primary outcome was 0.62 (p = 0.04;
      95% CI, 0.39-0.99) at 6 hours and 0.63 (p = 0.02; 95% CI, 0.42-0.93) at 24 hours.
      DATA SYNTHESIS: Fragility Index calculations for the primary outcomes of this
      trial were 1 and 2. Therefore, only one and two children would have needed
      different outcomes to have given nonsignificant p values greater than 0.05.
      Analysis of the results did not support the early stopping of this trial at the
      interim period. CONCLUSIONS: The article reviewed does not support a change in
      practice to a longer duration of fluid bolus. The "push" technique for titration
      of fluid boluses in pediatric septic shock should continue to be the method of
      choice. Critical Care trials using binary outcomes as endpoints should publish
      Fragility Index results to aid interpretation and generate stronger conclusions.

PMID- 29369076
TI  - Analysis of Pediatric Trauma in Combat Zone to Inform High-Fidelity Simulation
      Predeployment Training.
AB  - OBJECTIVES: The military uses "just-in-time" training to refresh deploying
      medical personnel on skills necessary for medical and surgical care in the
      theater of operations. The burden of pediatric care at Role 2 facilities has yet
      to be characterized; pediatric predeployment training has been extremely limited
      and primarily informed by anecdotal experience. The goal of this analysis was to
      describe pediatric care at Role 2 facilities to enable data-driven development of
      high-fidelity simulation training and core knowledge concepts specific to the
      combat zone. SETTING AND PATIENTS: A retrospective review of the Role 2 Database
      was conducted on all pediatric patients (< 18 yr) admitted to Role 2 in
      Afghanistan from 2008-2014. INTERVENTIONS: Three cohorts were determined based on
      commercially available simulation models: Group 1: less than 1 year, Group 2: 1-8
      years, Group 3: more than 8 years. The groups were sub-stratified by point of
      injury care, pre-hospital management, and Role 2 facility medical/surgical
      management. MEASUREMENTS AND MAIN RESULTS: Appropriate descriptive statistics
      (chi square and Student t test) were utilized to define demographic and
      epidemiologic characteristics of this population. Of 15,404 patients in the Role
      2 Database, 1,318 pediatric subjects (8.5%) were identified. The majority of
      patients were male (80.0%) with a mean age of 9.5 years (+/- SD, 4.5). Injury
      types included: penetrating (56%), blunt (33%), and burns (7%). Mean transport
      time from point of injury to Role 2 was 198 minutes (+/-24.5 min). Mean Glasgow
      Coma Scale and Revised Trauma Score were 14 (+/- 0.1) and 7.0 (+/- 1.4),
      respectively. Role 2 surgical procedures occurred for 424 patients (32%). Overall
      mortality was 4% (n = 58). CONCLUSIONS: We have described the epidemiology of
      pediatric trauma admitted to Role 2 facilities, characterizing the spectrum of
      pediatric injuries that deploying providers should be equipped to manage. This
      analysis will function as a needs assessment to facilitate high-fidelity
      simulation training and the development of "pediatric trauma core knowledge
      concepts" for deploying providers.

PMID- 29369078
TI  - Thromboelastographic study of the snakebite-related coagulopathy in Djibouti.
AB  - : Hemostasis disorders are one of the major clinical conditions of snakebites and
      are because of mechanisms which may disrupt vessels, platelets, clotting factors
      and fibrinolysis. Thromboelastography (TEG) could help to understand these
      effects in the clinical practice. A retrospective study reports a series of
      patients presenting a snakebite-related coagulopathy, treated with antivenom and
      monitored with conventional tests and TEG in a French military treatment facility
      (Republic of Djibouti, East Africa) between August 2011 and September 2013.
      Conventional coagulation assays (platelets, prothrombin time, activated partial
      thromboplastin time, fibrinogen) and TEG measurements were taken on arrival and
      at various times during the first 72 h of hospitalization, at the discretion of
      the physician. The study included 14 patients (median age 28 years). Bleedings
      were present in five patients. All patients received antivenom. A coagulopathy
      was present in all patients and was detected by both conventional assays and TEG.
      None exhibited thrombocytopenia. Prothrombin time and fibrinogen remained
      abnormal for most of patients during the first 72 h. The TEG profiles of 11
      patients (79%) showed incoagulability at admission (R-time > 60 min). TEG
      distinguished 10 patients with a generalized clotting factor deficiency and 4
      patients with an isolated fibrinogen deficiency after an initial profile of
      incoagulability. Hyperfibrinolysis was evident for 12 patients (86%) after Hour
      6. Snake envenomations in Djibouti involve a consumption coagulopathy in
      conjunction with delayed hyperfibrinolysis. TEG could improve medical management
      of the condition and assessment of additional therapeutics associated with the
      antivenom.

PMID- 29369079
TI  - Safety and effectiveness of high-dose, weight-based factor VIII inhibitor
      bypassing activity for warfarin-induced life-threatening bleeding.
AB  - : Previous studies suggest low, fixed-dose regimens of activated prothrombin
      complex concentrate [factor VIII inhibitor bypassing activity (FEIBA); 500 U for
      international normalized ratio (INR) < 5; 1000 U for INR > 5] is effective for
      reversal of warfarin-induced life-threatening bleeds. Little data are available
      on the use of high-dose, weight-based FEIBA for this indication. The objective of
      this study was to evaluate effectiveness and safety of high-dose, weight-based
      FEIBA (50 U/kg) vs. frozen plasma alone in this population. This was a matched
      case-control, multicenter retrospective study including patients who received
      high-dose, weight-based FEIBA or frozen plasma alone for warfarin-induced life
      threatening bleeds matched (1 : 1) based on age and bleed location. Forty-eight
      patients were included in the analysis (24 FEIBA, 24 frozen plasma). The primary
      endpoint was time to INR less than 1.5 after administration of FEIBA or frozen
      plasma. Secondary endpoints include rates of thromboembolic events and mortality.
      Median baseline INR was 3.7 (interquartile range 2.7, 7.30) and 2.9 (2.3, 6.61)
      in the FEIBA and frozen plasma groups, respectively (P = 0.13). Median FEIBA dose
      was 4530 (3672, 5028) U. Use of FEIBA resulted in faster time to INR less than
      1.5 with a median of 2.5 (1.25, 4.15) vs. 12 (5.6, 28.35) h; (P < 0.0001).
      Thromboembolic events occurred in nine (16.7%) patients (FEIBA n = 5; plasma n =
      4); (P = 1.0). Mortality was similar in both groups (FEIBA 33% vs. frozen plasma
      15%; P = 0.2). The use of high-dose, weight-based FEIBA resulted in faster time
      to reversal of warfarin-induced coagulopathy compared with frozen plasma alone
      and showed a similar safety profile.

PMID- 29369080
TI  - Coagulation assays in a case of apixaban overdose.
AB  - : Intentional overdose of apixaban is rare and minimal data exist regarding the
      usefulness of routinely available laboratory tests to predict drug levels. A 50
      year-old man was admitted after ingestion of 200-mg apixaban. Serial blood
      samples were obtained over a 54-h period for assessment of the fall-off in drug
      levels using the prothrombin time/international normalized ratio and anti-Xa
      assays and compared with an apixaban-specific chromogenic assay. The prothrombin
      time/international normalized ratio and anti-Xa assays correlated with the
      apixaban level when the drug was in the supratherapeutic range (>130 ng/ml) but
      not in the typical therapeutic trough to peak levels. Apixaban levels are best
      assessed by a specific anti-Xa test using optimized chromogenic substrates and
      specific calibrators. A standard anti-Xa test can be a useful surrogate when drug
      levels are high but use of a specific threshold level for discharge purposes
      requires caution.

PMID- 29369081
TI  - A retrospective evaluation of the age-adjusted D-dimer versus the conventional D
      dimer for pulmonary embolism.
AB  - : The conventional D-dimer cut-off value of at least 500 MUg FEU/l has good
      sensitivity but poor specificity for identifying pulmonary embolism. An elevated
      age-adjusted D-dimer value (age in years * 10 MUg FEU/l) for patients at least 50
      years old has been recommended as a better cut-off with adequate sensitivity and
      improved specificity for identifying pulmonary embolism compared with the
      conventional value. We retrospectively reviewed 3117 patient encounters in which
      a D-dimer was ordered. The D-dimer value, age of the patient, and the computed
      tomography radiology report was evaluated. The sensitivity and specificity of the
      age-adjusted D-dimer was calculated using bootstrapping. With an assumed 99%
      sensitivity for the conventional D-dimer cut-off the specificity was 39.2% [95%
      confidence interval (CI): 37.5-41.0%]. The sensitivity of the age-adjusted D
      dimer was 91.8% (95% CI: 83.8-97.2%) with a specificity of 51.0% (95% CI: 49.1
      53.1%). The sensitivity of the age-adjusted D-dimer was unacceptably low compared
      with the conventional D-dimer cut-off.

PMID- 29369082
TI  - Compliance with the 2009 Royal College of Obstetricians and Gynaecologists
      guidelines for venous thromboembolic disease prophylaxis in pregnancy and
      postpartum period in Uruguay.
AB  - : Venous thromboembolism remains as one of the leading causes of maternal death.
      Prevention of venous thromboembolism in the obstetric population is challenging
      as recommendations for prophylaxis have low grade of evidence. Risk factors and
      prophylaxis guidelines have been highlighted by Royal College of Obstetricians
      and Gynaecologists. In 2014, we developed a written alert following this
      guidelines to guide thromboprophylaxis. The aim of this study is to assess
      recommendations compliance. This study was conducted at University-Hospital in
      Uruguay from January 2014 to December 2016. A total of 1035 women were enrolled
      and stratified in high, intermediate or low risk based on Royal College of
      Obstetricians and Gynaecologists guidelines. Thromboprophylaxis was recommended
      for women at intermediate and high risk. Women were followed up to assess
      symptomatic thromboembolism or haemorrhagic complications. A total of 309 were
      pregnant and 731 puerperal. Median age was 24 (19-29) years old. Of them, 3.0% (n
      = 31) were at high risk and 35.4% (n = 366) at intermediate risk. All high-risk
      women received prophylaxis with low-molecular-weight heparin. Of the 366
      intermediate-risk women, 52.7% received prophylaxis. Venous thromboembolism was
      developed in only one woman of the intermediate group, who had received
      prophylaxis. Bleeding complications were not observed. Awareness of the
      thrombotic risk, as conferred by an easy and suitable risk assessment, has the
      potential to improve venous thromboembolism prophylaxis in pregnant and puerperal
      women. We have a good guidelines compliance with the written alert in the high
      risk women group. However, we have to improve low-molecular-weight heparin
      indication in intermediate-risk group, especially in postcaesarean women.

PMID- 29369083
TI  - Influence of ABO blood group on von Willebrand factor tests in healthy Saudi
      blood donors.
AB  - : Von Willebrand disease is a common bleeding disorder. The wide variation in von
      Willebrand factor (VWF) levels between and within normal individuals highlights
      the clinical challenge of defining its cutoff value. Although studies on the
      influence of ethnicity on ABO phenotypes and the levels of VWF have been carried
      out on different ethnicities, there is a lack of such data among Arab population.
      We aimed to evaluate the correlation of ABO phenotypes with all the parameters of
      the minimal test panel of VWF including VWF antigen, VWF activity using the
      ristocetin cofactor and the collagen binding activity assays, and factor VIII
      coagulant activity (VWF:Ag, VWF:RCo, VWF:CB and FVIII:C) tested in a normal Arab
      population, and to estimate ABO-specific normal reference range. Blood samples
      were collected from 87 healthy donors in Riyadh to determine levels of factor
      VIII and VWF panel between the various ABO phenotypes. The highest mean values of
      factor VIII : C (128 U/dl), VWF : Ag (125 U/dl), VWF : RCo (109 U/dl) and VWF :
      CB (91 U/dl) were observed with type AB and the lowest mean values of factor VIII
      : C (81 U/dl), VWF : Ag (85 U/dl), VWF : RCo (73 U/dl) and VWF : CB (70 U/dl)
      corresponded to type O. ABO phenotypes significantly influence plasma levels of
      VWF parameters in Arab nations as seen with other ethnicity. Hence, ABO-specific
      normal ranges of the minimal test panel of VWF and factor VIII : C are essential
      for the appropriate prediction of mild von Willebrand disease. Further study
      including a larger categorized sample size is required to generalize the test
      panel on the Arab population.

PMID- 29369084
TI  - DIRECTIONAL VARIABILITY OF FUNDUS REFLECTANCE IN ACUTE MACULAR NEURORETINOPATHY:
      EVIDENCE FOR A CONTRIBUTION OF THE STILES-CRAWFORD EFFECT.
AB  - PURPOSE: To document directional reflectivity of fundus lesions in a case of
      acute macular neuroretinopathy. METHODS: Case report. Clinical and imaging data
      from a patient with acute macular neuroretinopathy were reviewed. Imaging
      comprised infrared scanning laser ophthalmoscopy, optical coherence tomography
      and flood-illumination adaptive optics images acquired through different entry
      pupils in the cardinal directions (approximately 2 degrees  eccentricity).
      RESULTS: The patient reported acute bilateral paracentral scotoma revealing dark,
      wedge-shaped macular plaques which by optical coherence tomography were
      associated with focal loss of the visibility of the cone outer segment tip and
      inner/outer segment lines. Comparing scanning laser ophthalmoscopy images taken
      at different entry points in the pupil showed that macular plaques varied from
      hyporeflectance to isoreflectance. Cone counts by flood-illumination adaptive
      optics within plaques and optical coherence tomography features of the cone outer
      segment tip showed also a strong directional variability, peaking at near-normal
      values. Within each modality, fusion images showed that directional variability
      covered most of macular plaques. CONCLUSION: The characteristic fundus
      abnormalities of acute macular neuroretinopathy may show a strong directional
      variability. Our findings suggest that the Stiles-Crawford effect may be an
      important factor in signs and symptoms of acute macular neuroretinopathy.

PMID- 29369085
TI  - A Qualitative Study of the Influences on Clinical Academic Physicians'
      Postdoctoral Career Decision Making.
AB  - PURPOSE: To describe the influences on clinical academic physicians' postdoctoral
      career decision making. METHOD: Thirty-five doctoral trainee physicians from
      University College London took part in semistructured interviews in 2015 and
      2016. Participants were asked open-ended questions about their career to date,
      their experiences undertaking a PhD, and their career plans post PhD. The
      interviews were audio-recorded and transcribed. Thematic analysis was used to
      generate, review, and define themes from the transcripts. Emerging differences
      and similarities in participants' reasons for pursuing a PhD were then grouped to
      produce typologies to explore how their experiences influenced their career
      decision making. RESULTS: Participants described four key reasons for undertaking
      a PhD, which formed the basis of the four typologies identified. These reasons
      included the following: to pursue a clinical academic career; to complete an
      extensive period of research to understand whether a clinical academic career was
      the desired path forward; to improve clinical career prospects; and to take a
      break from clinical training. CONCLUSIONS: These findings highlight the need to
      target efforts at retaining clinical academic physicians according to their
      reasons for pursuing a PhD and their subsequent experiences with the process.
      Those responsible for overseeing clinical training must be well informed of the
      long-term benefits of training academically qualified physicians. In light of
      current political uncertainty, universities, hospitals, and external agencies
      alike must increase their efforts to inspire and assuage early-career clinical
      academic physicians' fears regarding their academic future.

PMID- 29369086
TI  - Drawing Boundaries: The Difficulty in Defining Clinical Reasoning.
AB  - Clinical reasoning is an essential component of a health professional's practice.
      Yet clinical reasoning research has produced a notably fragmented body of
      literature. In this article, the authors describe the pause-and-reflect exercise
      they undertook during the execution of a synthesis of the literature on clinical
      reasoning in the health professions. Confronted with the challenge of
      establishing a shared understanding of the nature and relevant components of
      clinical reasoning, members of the review team paused to independently generate
      their own personal definitions and conceptualizations of the construct. Here, the
      authors describe the variability of definitions and conceptualizations of
      clinical reasoning present within their own team. Drawing on an analogy from
      mathematics, they hypothesize that the presence of differing "boundary
      conditions" could help explain individuals' differing conceptualizations of
      clinical reasoning and the fragmentation at play in the wider sphere of research
      on clinical reasoning. Specifically, boundary conditions refer to the practice of
      describing the conditions under which a given theory is expected to hold, or
      expected to have explanatory power. Given multiple theoretical frameworks,
      research methodologies, and assessment approaches contained within the clinical
      reasoning literature, different boundary conditions are likely at play. Open
      acknowledgment of different boundary conditions and explicit description of the
      conceptualization of clinical reasoning being adopted within a given study would
      improve research communication, support comprehensive approaches to teaching and
      assessing clinical reasoning, and perhaps encourage new collaborative
      partnerships among researchers who adopt different boundary conditions.

PMID- 29369087
TI  - Evaluation Apprehension and Impression Management in Clinical Medical Education.
AB  - Historically, clinical medical education has relied on subjective evaluations of
      students and residents to judge their clinical competence. The uncertainty
      associated with these subjective clinical evaluations has produced evaluation
      apprehension among learners and attempts to manage one's professional persona
      (impression management) among peers and supervisors. Such behavior has been
      documented from antiquity through the Middle Ages to the present, including in
      two new qualitative studies in this issue of Academic Medicine on the social
      psychology of clinical medical education. New approaches to medical education,
      including competency-based education, mastery learning, and assessment methods
      that unite evaluation and education, are slowly changing the culture of clinical
      medical education. The author of this Invited Commentary argues that this shift
      will bring greater transparency and accountability to clinical medical education
      and gradually reduce evaluation apprehension and the impression management
      motives it produces.

PMID- 29369088
TI  - Free flaps for head and neck cancer in paediatric and neonatal patients.
AB  - PURPOSE OF REVIEW: To review recent literature on the subject of free tissue
      transfer options in paediatric head and neck surgery, with a particular emphasis
      on highlighting the advantages and disadvantages of different reconstructions in
      the paediatric patient. RECENT FINDINGS: Free tissue transfer in paediatric
      patients is predictable and applicable for a wide range of congenital and
      acquired defects in the head and neck. The free fibula flap is a mainstay of
      mandibular reconstruction and allows excellent implant-supported prosthodontic
      rehabilitation and growth potential at the recipient site with little or no donor
      site morbidity. Other less commonly explored options include the deep circumflex
      iliac artery flap, scapula flap and medial femoral condyle flap. The gracilis
      mucle remains the mainstay for facial reanimation with other options including
      pectoralis minor, rectus abdominis, extensor digitorum brevis and latissimus
      dorsi. There are compelling arguments for centralization of services and creative
      strategies in postoperative rehabilitation (e.g. play therapy). SUMMARY: Free
      flaps in paediatric patients are a viable option and may even have advantages
      relative to adults because of the absence of atherosclerosis, purported lower
      risk of vasospasm and proportionally larger vessel size. Transfer earlier in life
      maximizes functional potential and 'normalizes' treatment.

PMID- 29369089
TI  - Using technology to support clinical care and research in rheumatoid arthritis.
AB  - PURPOSE OF REVIEW: As digital technology becomes more ubiquitous, understanding
      the current state-of-the-art in digital information use for clinical care and
      research for patients with rheumatoid arthritis (RA) is timely and relevant.
      RECENT FINDINGS: The opportunities for recording and utilizing high-quality data
      from rheumatologists are reviewed, as well as opportunities from collecting,
      integrating and analysing patient-generated data to deliver a step-change in the
      support and management of RA. SUMMARY: Once greater adoption, standardization and
      implementation of relevant RA measures are in place within electronic health
      records (EHRs), patient care will improve and the ability to learn from aggregate
      experiences increases dramatically. Incorporating passive and patient-reported
      outcomes into self-management apps and integrating such data into the patient's
      health record will provide more responsive and better treatment results.

PMID- 29369090
TI  - EASY-An Instrument for Surveillance of Physical Activity in Youth.
AB  - PURPOSE: Physical activity (PA) promotion among youth is a public health
      priority, and there is a need for robust surveillance systems to help support
      such initiatives. Existing youth PA self-report instruments that are used for
      surveillance lack information regarding the types and contexts of activity.
      Further, these instruments have limited validity with accelerometry. The purpose
      of the present study was to develop a self-report instrument, with sound
      psychometric properties, for monitoring compliance with PA guidelines in youth.
      METHODS: In focus groups, 162 middle school students identified 30 forms of PA
      that are highly prevalent in that age-group. We incorporated these activities
      into three preliminary forms of a self-report instrument. An independent sample
      of middle school students (n = 537) was randomly assigned to complete one of the
      three preliminary versions of the instrument. Rasch analysis was applied to the
      responses to the three formats, and a yes/no plus frequency format emerged as the
      preferred method. A third sample of 342 middle school students then completed the
      yes/no plus frequency instrument twice after a 7-d period during which they wore
      an accelerometer. Using both Rasch analysis and traditional correlational
      methods, validity and reliability of a 14-item instrument were established. Data
      were collected during 2012-2015. RESULTS: Spearman correlation coefficient for
      the association between the cumulative score for the 14 items and minutes per day
      of accelerometry-derived moderate-to-vigorous physical activity was 0.33 (95%
      confidence interval = 0.22-0.43, P < 0.001). The sensitivity and specificity
      values of the 14-item instrument were 0.90 and 0.44, respectively. CONCLUSIONS:
      The study produced a PA self-report instrument for youth that was found to be
      reliable (r = 0.91), valid versus accelerometry (r = 0.33), and with acceptable
      specificity and sensitivity in detecting compliance with PA guidelines.

PMID- 29369091
TI  - Comparison of Intranasal Dexmedetomidine and Oral Pentobarbital Sedation for
      Transthoracic Echocardiography in Infants and Toddlers: A Prospective,
      Randomized, Double-Blind Trial.
AB  - BACKGROUND: Acquisition of transthoracic echocardiographic (TTEcho) images in
      children often requires sedation. The optimal sedative for TTEcho has not been
      determined. Children with congenital heart disease are repeatedly exposed to
      sedatives and anesthetics that may affect brain development. Dexmedetomidine,
      which in animals alters brain structure to a lesser degree, may offer advantages
      in this vulnerable population. METHODS: A prospective, randomized, double-blind
      trial enrolled 280 children 3-24 months of age undergoing outpatient TTEcho,
      comparing 2.5 ug.kg intranasal dexmedetomidine to 5 mg.kg oral pentobarbital.
      Rescue sedation, for both groups, was intranasal dexmedetomidine 1 ug.kg. The
      primary outcome was adequate sedation within 30 minutes without rescue sedation,
      assessed by blinded personnel. Secondary outcomes included number of sonographer
      pauses, image quality in relation to motion artifacts, and parental satisfaction.
      RESULTS: Success rates with a single dose were not different between sedation
      techniques; 85% in the pentobarbital group and 84% in the dexmedetomidine group
      (P = .8697). Median onset of adequate sedation was marginally faster with
      pentobarbital (16.5 [interquartile range, 13-21] vs 18 [16-23] minutes for
      dexmedetomidine [P = .0095]). Time from drug administration to discharge was not
      different (P = .8238) at 70.5 (64-83) minutes with pentobarbital and 70 (63-82)
      minutes with dexmedetomidine. Ninety-five percent of sedation failures with
      pentobarbital and 100% of dexmedetomidine failures had successful rescue sedation
      with intranasal dexmedetomidine. CONCLUSIONS: Intranasal dexmedetomidine was
      comparable to oral pentobarbital sedation for TTEcho sedation in infants and did
      not increase the risk of clinically important adverse events. Intranasal
      dexmedetomidine appears to be an effective "rescue" sedative for both failed
      pentobarbital and dexmedetomidine sedation. Dexmedetomidine could be a safer
      option for repeated sedation in children, but further studies are needed to
      assess long-term consequence of repeated sedation in this high-risk population.

PMID- 29369092
TI  - American Society for Enhanced Recovery and Perioperative Quality Initiative Joint
      Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced
      Recovery Pathway.
AB  - Perioperative malnutrition has proven to be challenging to define, diagnose, and
      treat. Despite these challenges, it is well known that suboptimal nutritional
      status is a strong independent predictor of poor postoperative outcomes. Although
      perioperative caregivers consistently express recognition of the importance of
      nutrition screening and optimization in the perioperative period, implementation
      of evidence-based perioperative nutrition guidelines and pathways in the United
      States has been quite limited and needs to be addressed in surgery-focused
      recommendations. The second Perioperative Quality Initiative brought together a
      group of international experts with the objective of providing consensus
      recommendations on this important topic with the goal of (1) developing
      guidelines for screening of nutritional status to identify patients at risk for
      adverse outcomes due to malnutrition; (2) address optimal methods of providing
      nutritional support and optimizing nutrition status preoperatively; and (3)
      identifying when and how to optimize nutrition delivery in the postoperative
      period. Discussion led to strong recommendations for implementation of routine
      preoperative nutrition screening to identify patients in need of preoperative
      nutrition optimization. Postoperatively, nutrition delivery should be restarted
      immediately after surgery. The key role of oral nutrition supplements, enteral
      nutrition, and parenteral nutrition (implemented in that order) in most
      perioperative patients was advocated for with protein delivery being more
      important than total calorie delivery. Finally, the role of often-inadequate
      nutrition intake in the posthospital setting was discussed, and the role of
      postdischarge oral nutrition supplements was emphasized.

PMID- 29369094
TI  - Using the Ventrain With a Small-Bore Catheter: Ventilation or Just Oxygenation?

PMID- 29369093
TI  - Age Does Not Affect Metoprolol's Effect on Perioperative Outcomes (From the POISE
      Database).
AB  - BACKGROUND: Perioperative beta-blockade reduces the incidence of myocardial
      infarction but increases that of death, stroke, and hypotension. The elderly may
      experience few benefits but more harms associated with beta-blockade due to a
      normal effect of aging, that of a reduced resting heart rate. The tested
      hypothesis was that the effect of perioperative beta-blockade is more significant
      with increasing age. METHODS: To determine whether the effect of perioperative
      beta-blockade on the primary composite event, clinically significant hypotension,
      myocardial infarction, stroke, and death varies with age, we interrogated data
      from the perioperative ischemia evaluation (POISE) study. The POISE study
      randomly assigned 8351 patients, aged >=45 years, in 23 countries, undergoing
      major noncardiac surgery to either 200 mg metoprolol CR daily or placebo for 30
      days. Odds ratios or hazard ratios for time to events, when available, for each
      of the adverse effects were measured according to decile of age, and interaction
      term between age and treatment was calculated. No adjustment was made for
      multiple outcomes. RESULTS: Age was associated with higher incidences of the
      major outcomes of clinically significant hypotension, myocardial infarction, and
      death. Age was associated with a minimal reduction in resting heart rate from
      84.2 (standard error, 0.63; ages 45-54 years) to 80.9 (standard error, 0.70; ages
      >85 years; P < .0001). We found no evidence of any interaction between age and
      study group regarding any of the major outcomes, although the limited sample size
      does not exclude any but large interactions. CONCLUSIONS: The effect of
      perioperative beta-blockade on the major outcomes studied did not vary with age.
      Resting heart rate decreases slightly with age. Our data do not support a
      recommendation for the use of perioperative beta-blockade in any age subgroup to
      achieve benefits but avoid harms. Therefore, current recommendations against the
      use of beta-blockers in high-risk patients undergoing noncardiac surgery apply
      across all age groups.

PMID- 29369095
TI  - The Effects of Agrin Isoforms on Diabetic Neuropathic Pain in a Rat
      Streptozotocin Model.
AB  - BACKGROUND: Diabetes mellitus affects 9.3% of the US population and increases
      risks of surgery and complications. Diabetic neuropathic pain (DNP), one of the
      main consequences of diabetes mellitus, is extremely difficult to treat. Current
      medications yield limited benefits and/or have severe adverse effects. Therefore,
      new, effective treatment is needed. METHODS: Streptozotocin at 55 mg/kg was
      injected intraperitoneally in rats to induce diabetes mellitus. Diabetic rats
      exhibiting neuropathic pain underwent intrathecal injection of purified agrin
      proteins at various doses and were then tested for tactile allodynia to evaluate
      whether DNP was inhibited. The agrin effects were also analyzed with patch-clamp
      recording on spinal cord slices. RESULTS: Fifty-kilo Dalton agrin (Agr50) at 0.2
      and 2 ng suppressed DNP when given intrathecally, while 25- and 75-kDa agrin
      (Agr25, Agr75) had little effect. The suppressive effect of Agr50 lasted 4 hours
      after a single bolus injection. The difference in effects of Agr50 on mean
      withdrawal threshold (4.6 +/- 2.2 g before treatment to 26 +/- 0 g after
      treatment) compared with that of Agr25 (4.9 +/- 2.0 g to 4.9 +/- 2.0 g) and Agr75
      (5.3 +/- 2.3 g to 9.2 +/- 2.5 g) was highly significant (P < .01). On spinal cord
      slices, Agr50 increased spontaneous GABAergic current activities, suggesting
      increased spontaneous inhibitory postsynaptic currents and action potential
      firing rate from GABA neurons, whereas Agr25 and Agr75 had no such effect.
      CONCLUSIONS: Agr50 had a potent suppressive effect on DNP and increased
      spontaneous inhibitory postsynaptic currents and action potential firing rate
      from GABA neurons. Therefore, Agr50 may provide a potential therapy for DNP.

PMID- 29369096
TI  - Electroencephalography and Brain Oxygenation Monitoring in the Perioperative
      Period.
AB  - Maintaining brain function and integrity is a pivotal part of anesthesiological
      practice. The present overview aims to describe the current role of the 2 most
      frequently used monitoring methods for evaluation brain function in the
      perioperative period, ie, electroencephalography (EEG) and brain oxygenation
      monitoring. Available evidence suggests that EEG-derived parameters give
      additional information about depth of anesthesia for optimizing anesthetic
      titration. The effects on reduction of drug consumption or recovery time are
      heterogeneous, but most studies show a reduction of recovery times if anesthesia
      is titrated along processed EEG. It has been hypothesized that future EEG-derived
      indices will allow a better understanding of the neurophysiological principles of
      anesthetic-induced alteration of consciousness instead of the probabilistic
      approach most often used nowadays.Brain oxygenation can be either measured
      directly in brain parenchyma via a surgical burr hole, estimated from the venous
      outflow of the brain via a catheter in the jugular bulb, or assessed
      noninvasively by near-infrared spectroscopy. The latter method has increasingly
      been accepted clinically due to its ease of use and increasing evidence that near
      infrared spectroscopy-derived cerebral oxygen saturation levels are associated
      with neurological and/or general perioperative complications and increased
      mortality. Furthermore, a goal-directed strategy aiming to avoid cerebral
      desaturations might help to reduce these complications. Recent evidence points
      out that this technology may additionally be used to assess autoregulation of
      cerebral blood flow and thereby help to titrate arterial blood pressure to the
      individual needs and for bedside diagnosis of disturbed autoregulation.

PMID- 29369097
TI  - In Response.

PMID- 29369098
TI  - Intraoperative Assessment of the Relationship Between Nipple Circulation and
      Incision Site in Nipple-Sparing Mastectomy With Implant Breast Reconstruction
      Using the SPY Imaging System.
AB  - INTRODUCTION: Nipple-sparing mastectomy (NSM) and immediate breast reconstruction
      with gel implants have grown in popularity because of superior aesthetic
      outcomes. One risk of this procedure is overexcision of the flap leading to
      inadequate circulation in the breast envelope. METHODS: We investigated 17 cases
      of NSM and gel implant breast reconstruction. Patients were divided into an infra
      areolar incision group and a supra-areolar incision group. Nipple-areolar complex
      perfusion was evaluated using the SPY imaging system after NSM and gel implant
      breast reconstruction. We aimed to discover any relationships between the
      incision method and nipple-areolar complex (NAC) circulation in NSM and gel
      implant breast reconstruction. RESULTS: For successful breast surgery, awareness
      of the blood supply to the breast, especially the NAC, is very important. In our
      study, with the indocyanine green SPY imaging system, most ingress (arterial
      inflow) and egress (venous outflow) rates in the infra-areolar incision group
      were better than those in the supra-areolar incision group (P < 0.005).
      CONCLUSIONS: We have shown that an infra-areolar incision provides better blood
      flow following NSM and gel implant breast reconstruction. In our experience, in
      order to prevent the possible ischemia of NAC, we used the smaller gel implants,
      which is approximately 10 to 20 mL smaller than the original implant size
      measured by the sizer, if the egress rate of NAC is lower than 0.2. These
      findings have implications in the clinical setting as surgeons have a choice to
      provide a better outcome for patients.

PMID- 29369099
TI  - Lymphangiomatous Tumors of the Neck: Tips to Avoid Iatrogenic Nerve Injuries in
      the Brachial Plexus Region.
AB  - Lymphangiomas are rare malformations of the lymphatic system and can often be
      found in the neck region, where its proximity to the brachial plexus may cause
      compressive neuropathy and possible iatrogenic injuries during dissection. We
      report 4 cases of lymphangiomas with compression of the brachial plexus that were
      successfully removed without permanent nerve injuries and present a literature
      review of the preoperative approach and surgical techniques. A preoperative
      multidisciplinary approach can help surgeons predict what they may encounter
      during the surgery. A careful and stepwise dissection of the vital structures
      surrounding the tumor, especially the brachial plexus anatomy, is critical to
      avoiding severe complications. Incomplete resection or leakage of the lymph could
      result in higher rate of recurrence.

PMID- 29369100
TI  - Successful Treatment of Plantar Hyperkeratosis in the Form of Recurrent Corns
      With Split-Thickness Sole Skin Graft.
AB  - INTRODUCTION: Plantar hyperkeratosis, such as corns and calluses, is common in
      older people and associated with pain, mobility impairment, and functional
      limitations. It usually develops on the palms, knees, or soles of feet,
      especially under the heels or balls. There are several treatment methods for
      plantar hyperkeratosis, such as salicylic acid plaster and scalpel debridement,
      and conservative modalities, such as using a shoe insert and properly fitting
      shoes. METHODS: We present an effective method of reconstructing the wound after
      corn excision using a split-thickness sole skin graft (STSSG). We harvested the
      skin graft from the arch of the sole using the dermatome with a skin thickness of
      14/1000th inches. RESULTS: Because the split-thickness skin graft, harvested from
      the sole arch near the distal sole, is much thicker than the split-thickness skin
      graft from the thigh, it is more resistant to weight and friction. The healed
      wound with STSSG coverage over the distal sole was intact, and the donor site
      over the sole arch had healed without complication during the outpatient follow
      up, 3 months after surgery. CONCLUSIONS: The recovery time of STSSG for corn
      excision is shorter than that with traditional treatment. Therefore, STSSG can be
      a reliable alternative treatment for recurrent palmoplantar hyperkeratosis.

PMID- 29369101
TI  - Course Review: Plastic Surgery for Surgical Trainees.
AB  - Early in their careers, trainees contemplating a career in plastic surgery may
      have limited specialty experience. Courses can provide valuable insight into
      specialty training and help develop necessary basic skills. However, this is not
      without a significant financial burden.Plastic Surgery for Surgical Trainees is a
      1-day course that only costs L50 GBP (US $65). Accredited by the Royal College of
      Surgeons, this course held in Bristol, United Kingdom, offers an inexpensive
      practical introduction toward plastic surgical techniques for trainees interested
      in plastic surgery and those in other surgical specialties. In this review, we
      provide an evaluation of the course.

PMID- 29369102
TI  - Does Brow Lift Add Risk to Blepharoplasty? Answers From a Multicenter Analysis of
      6126 Patients Undergoing Aesthetic Eye Surgery.
AB  - BACKGROUND: Brow lift is frequently combined with blepharoplasty; however, the
      literature is lacking on their combined effect on complication rates. OBJECTIVES:
      This study aims to evaluate major complication rates after blepharoplasty and
      brow lift and to determine if complication rates increase when blepharoplasty and
      brow lift were performed simultaneously. METHODS: A prospective cohort of
      patients who underwent cosmetic blepharoplasty, brow lift, or a combination of
      the 2 procedures between 2008 and 2013 was identified from the CosmetAssure
      Insurance database. The primary outcome was a postoperative major complication
      requiring emergency room evaluation, hospital admission, or reoperation within 30
      days. Groups were compared with univariate analysis (significance, P < 0.05).
      RESULTS: A total of 6126 patients underwent aesthetic eye surgery, of which, 4879
      (79.6%) underwent blepharoplasty, 441 (7.2%) brow lift, and 806 (13.2%) a
      combination the 2 procedures. Patients who underwent a combined procedure were
      older than patients who underwent isolated blepharoplasty or brow lift (55.5 +/-
      9.4 vs 54.6 +/- 11.1 vs 53.3 +/- 12.0 years; P < 0.01). In males, blepharoplasty
      was the most commonly performed procedure, followed by a combined procedure and
      brow lift (17.6% vs 12.9% vs 10.7%; P < 0.01). There were similar rates of
      smokers between the 3 groups (5.7% vs 8.0% vs 6.6%; P = 0.06). Between combined
      procedures, blepharoplasty, and brow lift there, were similar rates of major
      complications (0.4% vs 0.4% vs 0.7%; P = 0.65) and hematoma (0.2% vs 0.2% vs
      0.5%; P = 0.49), which was the most common complication. CONCLUSIONS: Aesthetic
      eye surgery has a very low overall major complication rate (0.4%). When brow lift
      is combined with blepharoplasty, it poses no additional risk of major
      complications compared with either procedure alone.

PMID- 29369103
TI  - Antegrade Intramedullary Pinning in Subacute Fifth Metacarpal Neck Fracture After
      Failed Conservative Treatment: A Prospective Comparative Study With Acute
      Fracture.
AB  - PURPOSE: The purposes of this study were to evaluate the efficacy of antegrade
      intramedullary pinning performed for neck fractures with angulations of over 30
      degrees after failed conservative treatment during the subacute phase and to
      compare the radiologic and clinical results with those of acute fractures with
      angulations of over 30 degrees treated via the same procedure. METHODS: Seventy
      three patients with a fifth metacarpal neck fracture were admitted to our
      institute between January 2010 and April 2015. Among them, 26 patients with an
      acute fracture (group 1) and 27 patients with a subacute fracture after failed
      conservative treatment who met the inclusion/exclusion criteria were
      investigated. After surgery, improvements in angulation and shortening, visual
      analog scale score for postoperative pain, Disabilities of the Arm, Shoulder, and
      Hand score, active range of motion, and grip strength were evaluated and
      compared. RESULTS: The mean durations of surgery from injury were 4.92 and 32.74
      days in groups 1 and 2, respectively, with a significant difference (P < 0.001).
      The preoperative amounts of angulation were 44.91 and 45.89 degrees, and the
      amounts of preoperative shortening were 3.31 and 3.44 mm, respectively, with no
      significant difference (P > 0.05). At the final follow-up, the angulation had
      definitively improved compared with before surgery in both groups (P < 0.001,
      both). However, there was a slight significant difference in terms of the
      residual angulation of 3.35 and 5.56 degrees in groups 1 and 2, respectively (P =
      0.02). Preoperative shortening was restored in both groups (P < 0.001, both) and
      the final state of residual shortening were similar (P = 0.06). The final visual
      analog scale scores, Disabilities of the Arm, Shoulder, and Hand scores, range of
      motion, and grip strength were all satisfactory in both groups without any
      significant difference. CONCLUSIONS: The failed treatment group, which had been
      predicted to obtain proper union through the initial use of conservative
      treatment, provided an adequate indication for noninvasive antegrade pinning. In
      addition, the current study suggested that closed reduction/immobilization
      remains a primary recommendation for angulated metacarpal neck fracture as long
      as careful observation is conducted if progression of the reduced fracture toward
      dorsal angulation is suspected.

PMID- 29369104
TI  - Three-Dimensional Analysis of Airway Change After LeFort III Midface Advancement
      With Distraction.
AB  - INTRODUCTION: LeFort III midface advancement using the distraction technique
      became the standard method for the correction of various craniofacial syndromes
      accompanied by the midface retrusion. Midface hypoplasia is known to be related
      to the imbalance in facial aesthetics, malocclusion, and the airway problem. This
      study aimed to evaluate the change in airway volume after performing a LeFort III
      midface advancement with the distraction techniques. PATIENTS AND METHODS:
      Between April 2008 and February 2013, 7 patients aged 5 to 7 years underwent
      standard LeFort III osteotomy, followed by distraction with a rigid external
      distractor with or without internal distractor. The degree of advancement of the
      midface and the airway volume were evaluated with 3-dimensional computed
      tomography scans and the 3-dimensional software. RESULTS: The average latent
      period was 3.57 days. The average manual distraction distance was 17.55 mm for
      3.82 weeks. The consolidation period ranged from 3 to 7 months. Changes between
      the preoperative and postoperative airway volumes were remarkable. The average
      preoperative postpharyngeal airway volume was 5649.33 mm compared with an average
      postoperative airway volume of 7403.44 mm. Therefore, the average postpharyngeal
      airway space increased by a remarkable 32.78%. CONCLUSIONS: This investigation
      revealed that the LeFort III midface advancement using distraction could increase
      postpharyngeal airway space by approximately 33% when the midface is advanced by
      approximately 18 mm. This method could be used as a future reference for LeFort
      III midface advancement with distraction.

PMID- 29369105
TI  - Monitoring of Myocutaneous Flaps by Measuring Capillary Glucose and Lactate
      Levels: Experimental Study.
AB  - INTRODUCTION: In surgery, certain defects require reconstruction with a
      microsurgical flap. The free flap failure rate varies between 2% and 5%. Vascular
      thrombosis is the most frequent complication and represents 15% to 73% of
      failures. The success rate of salvage therapy is greater when salvage surgery is
      early. Currently, clinical monitoring is the criterion standard but many
      noninvasive or minimally invasive techniques have been developed to improve early
      diagnosis of complications of vascular thrombosis. The aim of our experimental
      study was to compare clinical assessments with measurements of capillary glycemia
      and lactatemia during the monitoring of free flaps. MATERIALS AND METHODS:
      Myocutaneous latissimus dorsi flaps with skin paddles were created in pigs under
      general anesthesia. For each animal, 2 flaps were created (right and left) using
      the same technique. Four groups were made: group 1 (no flap ligation: control
      group), group 2 (flap with permanent ligation of the artery), group 3 (flap with
      permanent ligation of the two veins), group 4 (flap with transient ligation of
      the artery and 2 veins for 1 hour). The postoperative monitoring protocol
      consisted of monitoring the clinical, biological (glucose and lactate), and
      histological parameters. RESULTS: Eight animals were operated on and sixteen
      flaps were created. Each flap was clinically and biologically tested 25 times.
      Clinical, biological, and histological monitoring showed significant variations
      between the groups. The analysis of variance of capillary glycemia and lactatemia
      showed statistically significant difference between control group and group 2 (P
      < 0,0001), group 3 (P < 0,0001), or group 4 (P < 0,0001). There were no
      histological abnormalities after transient ligature at different times contrary
      to permanent ligature. DISCUSSION-CONCLUSION: Measuring capillary levels of
      lactate and glucose associated with clinical monitoring may shorten the time to
      diagnosis of flap failure. Ultimately, this will save lives and achieve better
      functional and aesthetic results.

PMID- 29369106
TI  - Evidence-Based Practice in Liposuction.
AB  - BACKGROUND: The goal of this study is to examine the existing peer reviewed
      literature comparing modern adjunctive techniques in liposuction including laser
      assisted liposuction (LAL) and ultrasound-assisted liposuction (UAL) to standard
      suction-assisted liposuction (SAL). We intend to interpret these findings into a
      literature-based clinical application to influence practice patterns. METHODS: A
      literature review was conducted using a keyword search in PubMed. Keyword search
      items included liposuction, lipoplasty, suction assisted liposuction, ultrasound
      assisted liposuction, laser assisted liposuction, tumescent, liposuction
      comparison, liposuction review, and combinations therein. Exclusion criteria
      included articles with a primary focus on histologic effects of energy devices,
      primary animal models, primary opinion papers with no reference to available
      data, and industry-sponsored publications. Inclusion criteria included articles
      with direct comparison of liposuction modalities, randomized or blinded studies,
      and studies with objective outcomes. RESULTS: Twenty-five articles that met the
      inclusion criteria comparing SAL to UAL or LAL out of 9972 articles identified
      were obtained. The selected literature was assigned into 3 categories: evidence
      demonstrating an advantage of 1 modality (SAL, UAL, or LAL) over another,
      evidence that showed no benefit of 1 modality over another, and evidence that
      demonstrated risks of complications of 1 modality over another. CONCLUSIONS: The
      benefits of UAL and LAL over SAL include the following: (1) UAL over SAL in the
      treatment of gynecomastia, (2) LAL and UAL over SAL with decreased
      hemoglobin/hematocrit in high-volume lipoaspirates, and (3) LAL over SAL with
      skin tightening in select areas specifically the submental area. Otherwise, the
      literature demonstrates equivocal results among the described techniques with no
      clear benefit to set one apart from the other. There appears to be no
      demonstrable added benefit to the addition of either UAL or LAL that would urge a
      change in practice patterns outside the exceptions listed.

PMID- 29369107
TI  - Facelift Practice Evolution: Objective Implementation of New Surgical Techniques.
AB  - BACKGROUND: Facial rejuvenation is an elective procedure commonly performed to
      combat the consequences of normal aging. The senior author's practice initially
      consisted of traditional facelifts with superficial muscular apopneurotic system
      plication and/or superficial muscular apopneurotic system flap. After the
      development of the minimal access cranial suspension (MACS) technique by Tonnard
      et al., the senior author transitioned to an almost exclusive MACS facelift
      practice. The purpose of this study was to determine the efficacy of the MACS
      technique versus the traditional facelift approach and objectively incorporate
      these results into practice. METHODS: A retrospective cohort study design was
      performed to identify all patients who underwent a facelift by the senior author
      between January 1, 2013, and December 31, 2015. Patient demographics,
      comorbidities, type of procedure, complications, revision surgery, and objective
      surgeon satisfaction were among the parameters recorded. This was compared with
      an historical cohort of the senior author's earlier experience. RESULTS: There
      was a statistically significant decrease in the use of the MACS facelift
      procedure between this study and the senior authors' seminal study. Within this
      study cohort, compared with conventional facelift, the MACS technique was done on
      younger patients, proved to have significantly shorter operative time, mean
      follow up, and allowed for additional concurrent non-facial procedures when
      compared with the traditional approach (all comparisons significant at P < 0.05).
      However, continued postoperative neck laxity, submental pleating, and periocular
      pleating were seen with the MACS technique. CONCLUSIONS: The current study shows
      that the MACS technique is better suited for young patients with lesser cervical
      bulk or laxity and provides an opportunity for concurrent nonfacial procedures.
      Objective assessment with recognition of the limitations of the MACS technique
      versus the traditional facelift approach has led to a change in the senior
      author's practice. Although the MACS lift incurs shorter procedure time and
      quicker recovery, it does demonstrate limitations when it comes to marked skin
      laxity and bulky necks/platysmal banding. Both techniques are used with in line
      with the respective limitations and advantages.

PMID- 29369108
TI  - Safety of Microsurgery Under Loupes Versus Microscope: A Head-to-Head Comparison
      of 2 Surgeons With Similar Experiences.
AB  - BACKGROUND: Microsurgery is performed using either the operating microscope or
      loupe magnification. Use of the operating microscope is considered the "criterion
      standard"; however, loupes are emerging as a safe and reliable technique to
      perform microsurgery. The purpose of this study was to analyze the safety of
      microsurgery under loupe magnification compared with the microscope. Previous
      studies discussing the safety of loupe magnification during microsurgery have
      been published; however, this is the first study to compare free flap outcomes
      from 2 surgeons at the same institution, each using their respective technique.
      METHODS: The outcomes were compared by retrospective chart review of 116
      patients, and 148 microvascular free tissue transfers were performed between
      January 1, 2013, and July 15, 2016, by 2 surgeons (D.S.) and (M.L.). Patients'
      demographics, free flap failure rate, and other surgical complications were
      analyzed. Statistical significance was determined by unpaired t test, and chi
      analysis was used to determine statistical significance in proportions between
      groups. RESULTS: Thirty-eight percent of flaps were performed under *3.5 loupe
      magnification and 62% under the operating microscope. Most free flaps used were
      deep inferior epigastric perforator or muscle sparing transverse rectus abdominis
      flaps (52%) for breast reconstruction, remainder of free flaps included ALT,
      radial forearm, and latissimus dorsi for a variety of reconstructive
      applications. There was no significant difference between the loupes and
      microscope groups in intraoperative anastomotic revision rate (27% vs 17%),
      postoperative arterial or venous thrombosis (4.4% vs 2.6%, 5.4% vs 2.2%), flap
      loss (3.6% vs 2.2%), or median length of stay (6 days vs 6.5 days). The loupe
      magnification group had statistically significant shorter setup time (20 minutes,
      P < 0.01). CONCLUSIONS: Consistent with previously reported studies, we found no
      statistical difference in free flap outcomes and safety under loupe magnification
      compared with the operating microscope. This is the first study to demonstrate
      these findings with 2 microsurgeons both in their first 3 years in practice, with
      similar training and experience, operating at the same institution and given the
      same resources, each using either microscopes or loupes for microsurgery.

PMID- 29369109
TI  - Is Unipedicled Transverse Rectus Abdominis Myocutaneous Flap Obsolete Owing to
      Superiority of DIEP Flap?
AB  - BACKGROUND: Pedicled transverse rectus abdominis myocutaneous (TRAM) flap was
      developed by Hartrampf in 1982 for breast reconstruction. Since deep inferior
      epigastric perforator (DIEP) flap was popularized, it has become the criterion
      standard for abdominally based breast reconstruction owing to its low donor site
      morbidity, excellent cosmetic outcomes, and high success rates. The purpose of
      this review is to determine if a unilateral pedicle TRAM flap has become obsolete
      to DIEP flap. METHODS: Literature review was performed with key words DIEP flap,
      pedicled TRAM flap, and comparison of DIEP flap to unilateral pedicled TRAM flap.
      Specific journals reviewed were Plastic and Reconstructive Surgery and Annals of
      Plastic Surgery. Flaps were compared in the studies with respect to donor site
      morbidity, flap-related complications, operative time, length of hospital stay,
      patient satisfaction, and cost. RESULTS: Abdominal bulge and/or hernia were found
      to be statistically higher in pedicled TRAM patients in most of the studies
      reviewed. Also, uniformly flap fat necrosis rate was lower in DIEP patients. Rate
      of partial flap necrosis, total flap loss, hematoma, seroma, delayed healing, and
      infection varied in the studies with respect to both flaps without definitive
      trend towards specific flap technique. Overall patient satisfaction appeared to
      be higher in DIEP group in several studies. No significant differences between
      length of hospital stay, overall complication rates, and operative times between
      DIEP and unilateral pedicled TRAM patients were noted, and the results varied
      across different studies. Deep inferior epigastric perforator flap
      reconstructions were associated with higher overall cost in one study.
      CONCLUSIONS: In a carefully selected patient and circumstances where microsurgery
      is suboptimal, unipedicled TRAM flap can be a safe and viable option with
      satisfactory outcomes. It should continue to remain as part of core plastic
      surgery training and armamentarium of plastic surgeons in autologous breast
      reconstruction.

PMID- 29369110
TI  - Moffitt Cancer Center Experience of Tissue Expander Breast Reconstruction: Does
      Acellular Dermal Matrix Increase Return to the Operating Room?
AB  - BACKGROUND: Tissue expander and implant remains the most common technique for
      breast reconstruction. A controversial topic within this method is routine use of
      acellular dermal matrix (ADM). Acellular dermal matrices have increased risks of
      infection, seroma, hematoma, skin flap necrosis, and total complications.
      METHODS: After an institutional review board approval, a retrospective chart
      review was conducted of 756 tissue expander with implant cases from November 2010
      to November 2016 at Moffitt Cancer Center with 2 breast reconstruction surgeons.
      Patients were grouped in 2 groups: tissue expander alone reconstruction (TE) and
      tissue expander with ADM (TE + ADM). Complications were defined by return visits
      to the operating room for irrigation and debridement as well as for subsequent
      tissue expander placement. RESULTS: There were 703 patients in the TE group and
      53 in the TE + ADM group. Patients undergoing TE + ADM reconstruction were 3
      times more likely to experience return to operating room compared with patients
      undergoing TE alone (7.5% vs 2.4%). Patients were significantly more likely to
      undergo 3 or more subsequent tissue expander placement procedures with TE + ADM
      (54.7%) compared with TE alone (4.8%) (P < 0.0001). CONCLUSIONS: Although ADM may
      be appropriate for specific patients, its use in tissue expander breast
      reconstruction should be judiciously selected, because there is an observed
      increase in complications needing return to the operating room.

PMID- 29369111
TI  - The Impact of Perioperative Hormonal Therapy for Breast Cancer on Transverse
      Rectus Abdominis Myocutaneous Flap Abdominal Complications.
AB  - BACKGROUND: The pedicled transverse rectus abdominis myocutaneous (TRAM) flap is
      a reliable reconstructive option in breast cancer patients; however, it carries
      known risk of donor site hernia formation. Some hormonal therapy drugs have been
      associated with hernia formation in animal models. Minimal data exist concerning
      impact of hormonal therapy for breast cancer on abdominal donor site
      complications after breast reconstruction. METHODS: Patients who underwent TRAM
      flap for breast cancer or high-risk status at a single institution by the senior
      author from 2003 to 2015 were identified. Charts were reviewed. Patient
      demographics, comorbidities, treatments, and abdominal complications were
      recorded. Patients were divided into groups based on use of hormonal therapy as
      well as exposure to specific drugs. Statistical analyses were performed. RESULTS:
      A total of 358 patients were included. Overall hernia rate was 5.9%. About 231
      (64.5%) patients had hormonal therapy, whereas 127 (35.5%) did not. Difference in
      hernia formation was not statistically significant between the hormonal therapy
      group (6.9%) and the no hormonal therapy group (3.9%; P = 0.359). Patients
      exposed to tamoxifen and those exposed to anastrozole had no significant
      difference in complication rates compared with the no hormonal therapy group,
      whereas patients exposed to letrozole had increased rate of hernia (13.5%; P =
      0.037) and infection (21.6%; P = 0.013) compared with the no hormonal therapy
      group (3.9% and 7.1%, respectively). CONCLUSIONS: Hormonal therapy is a useful
      adjunct for chemoprevention in breast cancer; however, use of letrozole in
      patients undergoing reconstruction with pedicled TRAM can lead to increase in
      certain complication rates.

PMID- 29369112
TI  - Anisocytosis and leukocytosis are independently related to survival after
      transcatheter aortic valve replacement.

PMID- 29369113
TI  - The Influence of Presurgical Factors on the Rehabilitation Outcome of Patients
      Following Hip Arthroplasty.
AB  - PURPOSE: The aims of this study were to evaluate the relationship between
      sociodemographic information, anthropometric values, clinical and presurgery
      factors, and length of stay (LOS) in older adult patients undergoing total hip
      arthroplasty (THA) and to predict which factors can delay the start of the
      rehabilitation program and increase the corresponding LOS. METHODS: A prospective
      cohort study was conducted in an orthopedic inpatient unit with 40 patients
      undergoing THA. FINDINGS: The Morse Fall Scale scores and pain intensity scores
      delayed the commencement of the rehabilitation program. Gender and social support
      were important determinants of LOS and rehabilitation outcome following THA. The
      weight of the lower limb without osteoarthritis followed by pain intensity and
      overweight patients also influenced LOS. CONCLUSIONS/CLINICAL RELEVANCE:
      Functional outcomes after THA are variable, and the rehabilitation process is an
      important factor to regain their normal level of physical functioning. This
      factor can have an impact in the discharge of patients, in resource allocation
      and in health care of older adult patients.

PMID- 29369114
TI  - Resting energy metabolism and anticancer treatments.
AB  - PURPOSE OF REVIEW: Cachexia is a multifactorial syndrome associated with
      morbidity and mortality in cancer patients and represents a major challenge in
      cancer management. Elevated energy expenditure is supposed to contribute to
      cachexia. The current article presents the recent findings on the resting energy
      expenditure (REE) in cancer and the clinical implications for anticancer
      treatments. RECENT FINDINGS: Half of cancer patients present with hypermetabolism
      (measured REE >110% of predicted REE). Hypermetabolism is associated with
      clinical and biological features of cachexia. Hypermetabolic patients - even
      those with normal nutritional status - have a high risk of severe acute toxicity
      and a poor prognosis. SUMMARY: Recent discoveries have highlighted the REE as an
      essential component of nutritional assessment in cancer patients. Multimodal care
      for cachexia should include REE measurements and dedicated pharmacologic
      interventions such as adrenoreceptor blockade in case of hypermetabolism.

PMID- 29369115
TI  - Are the days of counting seizures numbered?
AB  - PURPOSE OF REVIEW: The estimation of seizure frequency is a cornerstone of
      clinical management of epilepsy and the evaluation of new therapies. Current
      estimation approaches are significantly limited by several factors. Comparing
      patient diaries and objective estimates (through both inpatient video-EEG
      monitoring of and long-term ambulatory EEG studies) reveal that patients document
      seizures inaccurately. So far, few practical alternative methods of estimation
      have been available. RECENT FINDINGS: We review the systems of counting currently
      utilized and their limitations, as well as the limitations imposed by problems
      defining clinical events. Alternative methodologies that permit the volatility of
      seizure rates to be accommodated, and possible alternative measures of brain
      excitability will be outlined. Recent developments in technologies around data
      capture, such as wearable and implantable devices, as well as significant
      advances in the ability to analyse the large data-sets supplied by these systems
      have provided a wealth of information. SUMMARY: There are now unprecedented
      opportunities to utilize and apply these insights in routine clinical management
      and assessment of therapies. The rapid adoption of long-term, wearable monitoring
      systems will permit major advances in our understanding of the natural history of
      epilepsy, and lead to more effective therapies and improved patient safety.

PMID- 29369116
TI  - Imaging Findings in Purtscher-Like Retinopathy Associated With Leukemia.

PMID- 29369117
TI  - Does goal-directed haemodynamic and fluid therapy improve peri-operative
      outcomes?: A systematic review and meta-analysis.
AB  - BACKGROUND: Much uncertainty exists as to whether peri-operative goal-directed
      therapy is of benefit. OBJECTIVES: To discover if peri-operative goal-directed
      therapy decreases mortality and morbidity in adult surgical patients. DESIGN: An
      updated systematic review and random effects meta-analysis of randomised
      controlled trials. DATA SOURCES: Medline, Embase and the Cochrane Library were
      searched up to 31 December 2016. ELIGIBILITY CRITERIA: Randomised controlled
      trials enrolling adult surgical patients allocated to receive goal-directed
      therapy or standard care were eligible for inclusion. Trauma patients and
      parturients were excluded. Goal-directed therapy was defined as fluid and/or
      vasopressor therapy titrated to haemodynamic goals [e.g. cardiac output (CO)].
      Outcomes included mortality, morbidity and hospital length of stay. Risk of bias
      was assessed using Cochrane methodology. RESULTS: Ninety-five randomised trials
      (11 659 patients) were included. Only four studies were at low risk of bias.
      Modern goal-directed therapy reduced mortality compared with standard care [odds
      ratio (OR) 0.66; 95% confidence interval (CI) 0.50 to 0.87; number needed to
      treat = 59; N = 52; I = 0.0%]. In subgroup analysis, there was no mortality
      benefit for fluid-only goal-directed therapy, cardiac surgery patients or
      nonelective surgery. Contemporary goal-directed therapy also reduced pneumonia
      (OR 0.69; 95% CI, 0.51 to 0. 92; number needed to treat = 38), acute kidney
      injury (OR 0. 73; 95% CI, 0.58 to 0.92; number needed to treat = 29), wound
      infection (OR 0.48; 95% CI, 0.37 to 0.63; number needed to treat = 19) and
      hospital length of stay (days) (-0.90; 95% CI, -1.32 to -0.48; I = 81. 2%). No
      important differences in outcomes were found for the pulmonary artery catheter
      studies, after accounting for advances in the standard of care. CONCLUSION: Peri
      operative modern goal-directed therapy reduces morbidity and mortality.
      Importantly, the quality of evidence was low to very low (e.g. Grading of
      Recommendations, Assessment, Development and Evaluation scoring), and there was
      much clinical heterogeneity among the goal-directed therapy devices and
      protocols. Additional well designed and adequately powered trials on peri
      operative goal-directed therapy are necessary.

PMID- 29369118
TI  - Administration of Cabergoline Contributes to Preserving Fertility in Young
      Hyperprolactinemic Patients With Endometrial Cancer Treated With
      Medroxyprogesterone Acetate.
AB  - BACKGROUND: An association between high levels of serum prolactin and endometrial
      cancer (EC) has been reported. However, the effect of antiprolactin drugs on
      hyperprolactinemic patients with EC has not been determined. The aim of this
      study was to confirm the effect of cabergoline on young hyperprolactinemic
      patients treated with medroxyprogesterone acetate (MPA) for the preservation of
      fertility. METHODS: A retrospective observational study was conducted to identify
      patients with atypical endometrial hyperplasia or early-stage EC aged 40 years or
      younger who were treated with oral MPA in Kumamoto University Hospital between
      1998 and 2016. RESULTS: Thirty-four patients were identified and divided into two
      groups of 17 patients each, including a nonadministration of cabergoline group
      (noncabergoline group) and an administration of cabergoline group (cabergoline
      group). The ratio of pathological diagnoses of EC in the noncabergoline group was
      significantly lower than that in the cabergoline group (29.4% vs 70.6%, P =
      0.016). The mean serum prolactin levels showed a significant decrease after the
      administration of cabergoline in the cabergoline group (25.2 [24.0] vs 5.2 [4.2]
      ng/mL, P = 0.003), and this decreased level was also significantly lower than
      that in the noncabergoline group (5.2 [4.2] vs 12.0 [5.0] ng/mL, P < 0.001).
      Kaplan-Meier analysis conducted for 150 months revealed that the estimated mean
      period until hysterectomy in the noncabergoline group was significantly shorter
      than that in the cabergoline group (83.5 vs 140.8 months, P = 0.007). Significant
      differences were observed in EC but not atypical endometrial hyperplasia based on
      histological classification (25.6 vs 138.0 months, P = 0.001). CONCLUSIONS: The
      administration of cabergoline may contribute to preserving fertility in young
      hyperprolactinemic patients with EC who were treated with MPA.

PMID- 29369119
TI  - Disease-Free and Survival Outcomes for Total Laparoscopic Hysterectomy Compared
      With Total Abdominal Hysterectomy in Early-Stage Endometrial Carcinoma: A Meta
      analysis.
AB  - OBJECTIVES: Laparoscopic hysterectomy is currently offered to a large number of
      patients, and assessing the noninferiority to abdominal hysterectomy with respect
      to clinical outcomes is key. We examine rates of recurrence, disease-free
      survival (DFS), and overall survival, and surgical complications of laparoscopic
      compared with abdominal hysterectomy for the treatment of early-stage endometrial
      cancer. METHODS: Electronic databases were systematically searched to identify
      relevant studies, and patient characteristics and clinical outcomes extracted.
      The primary outcome was 3-year DFS, and estimates were pooled using an inverse
      variance weighted meta-analysis. RESULTS: Nine studies (4405 patients) were
      identified in which DFS was reported in 5 studies. The difference in 3-year DFS
      was 1.44% (95% confidence interval [CI], -0.65% to 3.53%) in favor of total
      abdominal hysterectomy, consistent with a noninferiority margin of 5%.
      Differences in DFS (hazard ratio, 1.10; 95% CI, 0.92-1.32), overall survival
      (hazard ratio, 1.16; 95% CI, 0.81-1.66), and local recurrence (difference, 0.42%;
      95% CI, -0.41% to 1.25%) were not significant. Rates of intraoperative
      complications showed no difference (0.5%; 95% CI, -1.1% to 2.0%) based on 7
      studies. There was a significant reduction in postoperative complications with
      the laparoscopic procedure (-6.83%; 95% CI, -9.19% to -4.47%). CONCLUSIONS:
      Noninferiority of laparoscopy was demonstrated on clinical outcomes and was
      associated with a reduction in postoperative complications. These results support
      continued treatment by laparoscopic hysterectomy for early-stage endometrial
      cancer.

PMID- 29369120
TI  - Activity Behaviors and Physiological Characteristics of Women With Advanced-Stage
      Ovarian Cancer: A Preliminary Cross-sectional Investigation.
AB  - OBJECTIVES: Ovarian cancer (OC) survivors experience many disease and treatment
      adverse effects. However, the impact of OC and its treatment on objective
      activity behaviors and physiological status have not been examined. The purpose
      of this study was to compare objectively measured activity behaviors and
      physiological characteristics of advanced-stage OC survivors to age-matched
      controls. METHODS: Twenty stage III-IV OC survivors and 20 controls completed
      assessments of activity behaviors (7-day accelerometry), physical function (400
      meter walk as indicator of cardiorespiratory fitness, repeated chair rise, 6
      meter walking tests), muscle strength (1-repetition maximum and handgrip), body
      composition (dual-energy x-ray absorptiometry), and musculoskeletal morphology
      (peripheral quantitative computed tomography). RESULTS: Compared with controls,
      OC survivors spent more time/day in prolonged sedentary bouts (P = 0.039, r =
      0.32), had lower cardiorespiratory fitness (P = 0.041, r = 0.33) and upper body
      strength (P = 0.023, r = 0.37), had higher areal bone mineral content (P = 0.047,
      r = 0.33) and volumetric trabecular density (P = 0.048, r = 0.31), but were not
      different in other measures of body composition nor in muscle morphology (P >
      0.050). Only 20% (n = 4) of OC survivors accrued 150 minutes/week or greater
      moderate and vigorous physical activity (MVPA) time in 10-minute bouts or
      greater. Moderate and vigorous physical activity time/day in 10-minute bouts or
      greater was strongly associated with cardiorespiratory fitness (P = 0.001, rho = 
      0.702) and lower extremity function (P = 0.019, rho = -0.519) and moderately
      associated with muscle cross-sectional area (P = 0.035, rho = 0.473).
      CONCLUSIONS: Posttreatment OC survivors spent more time in prolonged sedentary
      bouts and had lower cardiorespiratory fitness and upper body strength compared
      with controls. Moderate and vigorous physical activity was associated with
      physical function and muscle cross-sectional area. Future studies should test the
      efficacy of exercise interventions to increase MVPA, reduce sedentary behavior,
      and increase cardiorespiratory fitness and muscle strength in OC survivors.

PMID- 29369121
TI  - Quality and Cultural Sensitivity of Linguistically Appropriate Cardiovascular
      Disease Information for Chinese Immigrants: A Review of Online Resources From
      Heart Foundations.
AB  - BACKGROUND: Chinese immigrants are at an increased risk for cardiovascular
      diseases (CVDs) compared with Chinese nationals partly because of lifestyle
      changes and knowledge deficits. Translated patient resources are available on the
      Internet and are often provided by health professionals; however, the quality and
      cultural sensitivity of these resources have not been reported. OBJECTIVE: The
      aim of this study was to assess the availability, quality, and cultural
      sensitivity of Chinese-language information available from national "Heart
      Foundations" (cardiac research bodies, nongovernmental organisations) of the 5
      most popular destinations of Chinese immigration. METHODS: This study is a
      descriptive research in which national "Heart Foundation" websites were
      systematically searched for Chinese-language CVD patient education resources.
      Quality (content, identification, structure) was assessed using the Ensuring
      Quality Information for Patients instrument. Cultural sensitivity was evaluated
      using the Cultural Sensitivity Assessment Tool. RESULTS: From 107 identified
      resources, 33 were CVD specific: coronary heart disease (n = 20), arrhythmias (n
      = 7), and heart failure (n = 6). Quality of resources was adequate (mean Ensuring
      Quality Information for Patients score, 69%), but scores varied significantly
      (min, 60%; max, 85%). Although all resources were classified as culturally
      sensitive (Cultural Sensitivity Assessment Tool score >= 2.5), 2 resources scored
      low (<=2.5) for visual impact, and across all resources, written and visual
      domains were assessed as least culturally sensitive. Most resources lacked
      culturally specific references. CONCLUSIONS: Chinese-language CVD resources were
      inconsistent in the supply of key information. Quality and level of cultural
      sensitivity were adequate, but most resources lacked culturally specific
      references. Comprehensive, high-quality CVD resources powered by Editorial
      Manager and ProduXion Manager from Aries Systems Corporation tailored for Chinese
      immigrants are urgently needed for healthcare providers to support CVD education
      and care of patients belonging to this population.

PMID- 29369122
TI  - Effects of Static Stretching Exercise on Lumbar Flexibility and Central Arterial
      Stiffness.
AB  - BACKGROUND: Previous studies have demonstrated that arterial stiffness is
      associated with lumbar flexibility (LF). Stretching exercise targeted to improve
      LF may have a beneficial effect on reducing arterial stiffness. OBJECTIVES: We
      examined the effects of a single bout of a structured, static stretching exercise
      on arterial stiffness, LF, peripheral and central blood pressure (BP), and heart
      rate (HR) and tested the association between LF and central arterial stiffness.
      METHOD: The study had a pretest-posttest design without a control group. Thirty
      healthy women followed a video demonstration of a 30-minute whole-body stretching
      exercise. Carotid-femoral pulse wave velocity (cf-PWV), augmentation index, LF,
      peripheral and central BP, and HR were measured before and after the stretching
      exercise. RESULTS: One bout of a static stretching exercise significantly reduced
      cf-PWV (t29 = 2.708, P = .011) and HR (t29 = 7.160, P = .000) and increased LF
      (t29 = 12.248, P < .000). Augmentation index and peripheral and central BP also
      decreased but did not reach statistical significance. Despite no association
      found between cf-PWV and LF, the larger increase in LF the subjects had, the
      larger decrease in cf-PWV they had after exercise (r = 0.500, P = .005).
      CONCLUSIONS: Study findings highlight the potential benefit of a static
      stretching exercise on central arterial stiffness, an independent predictor of
      cardiovascular morbidity. Static stretching exercise conducted in the sitting
      position may be used as an effective intervention to reduce cardiovascular risk
      after a cardiac event or for patients whose sympathetic function should not be
      overly activated or whose gaits are not stable.

PMID- 29369123
TI  - Effects of a Tablet Computer on Self-care, Quality of Life, and Knowledge: A
      Randomized Clinical Trial.
AB  - BACKGROUND: Conflicting results have been reported for telemonitoring in patients
      with heart failure (HF). We wanted to evaluate whether patients using a tablet
      computer aimed at improving self-care behavior could do so and also whether it
      affects quality of life and health-related quality of life, disease knowledge,
      and in-hospital days. METHODS AND RESULTS: Patients with HF (n = 82) were
      randomized to the intervention group (IG) with a tablet computer (giving
      information and advice) or the control group (CG) that was subject to standard
      care. Study was completed by 72 patients, with a mean (SD) age of 75 (8) years,
      68% male, and 74% NYHA class III. Self-care behavior measured with the 9-item
      European Heart Failure Self-Care Behaviour Scale, health related quality of life
      measured by the Kansas City Cardiomyopathy Questionnaire, quality of life
      measured by the Swedish version of the Health Survey, knowledge measured by the
      Dutch Heart Failure Knowledge Scale, days in hospital, and adherence were
      analyzed. The IG displayed better 9-item European Heart Failure Self-Care
      Behaviour Scale score (median IG, 16.5 [interquartile range {IQR}, 12-22], vs
      median CG, 23.5 [IQR, 18.8-30.0]; P < .05) and improved health related quality of
      life (median IG, 72.7 [IQR, 50.8-87.9], vs median CG, 51.8 [IQR, 40.9-62.8]; P <
      .05). A significant difference in knowledge was seen, with an 11% increase in IG
      and a 1% decrease in CG (P < .05), as well as a reduction in hospital days in IG
      by 2.7 days per patient (relative risk, 0.72; 95% confidence interval, 0.61-0.84;
      P < .05). CONCLUSION: The tablet computer significantly improved self-care
      behavior and health related quality of life, increased HF knowledge, and reduced
      hospital days.

PMID- 29369124
TI  - Are We Too Quick to Alter Our Practice Patterns Because of the Results of a
      Randomized Controlled Trial?

PMID- 29369125
TI  - Derotational Pronation-producing Osteotomy of the Radius and Biceps Tendon
      Rerouting for Supination Contractures in Neonatal Brachial Plexus Palsy Patients.
AB  - Forearm supination contractures can occur as a result of neurological derangement
      of the upper extremity. Primarily, this is observed in patients with neonatal
      brachial plexus birth palsy. The contractures develop slowly over time and become
      problematic in childhood as the patients begin requiring forearm pronation for
      activities of daily living including typing on a keyboard and writing. Although
      supination contracture is a well-described sequelae of neonatal brachial plexus
      birth palsy, there is a paucity of literature describing techniques and outcomes
      for reconstruction and restoration of forearm pronation. The initially described
      technique included release of the interosseous membrane for flexibility combined
      with rerouting of part of the biceps tendon to change its biomechanical pull from
      supination to pronation. More recently, bone and soft tissue procedures have been
      combined with various forearm osteotomies. We present a combined derotational
      radial osteotomy and biceps rerouting to realign the forearm in resting pronation
      and convert the biceps from a supinator to a pronator. This novel surgical
      technique has not been described as a solution for supination contracture to
      restore pronation and provide biomechanical advantage of the biceps insertion.

PMID- 29369126
TI  - New Beginnings.

PMID- 29369127
TI  - Caring for the Caregiver.

PMID- 29369129
TI  - MACRA and the Quality Payment Program: How Does It Relate to Orthopaedic Nursing?

PMID- 29369128
TI  - MACRA and the Quality Payment Program: How Does It Relate to Orthopaedic Nursing?
AB  - The introduction of 2017 also brought with it the beginning of the Medicare
      Access and CHIP Reauthorization Act of 2015 (MACRA) legislation related to the
      Quality Payment Program (QPP), in addition to alternative payment models and the
      merit-based incentive payment system. The successful implementation of the QPP
      within the specialty of orthopaedics will rely heavily on the active involvement
      of orthopaedic nurses when it comes to improving quality, lowering costs, and
      incorporating value. It is important for orthopaedic nurses to understand the QPP
      and the role it plays in determining value-based payment of orthopaedic care
      delivery, in addition to how the structure of the QPP correlates with nursing
      diagnoses and respective plans of care delivery.

PMID- 29369131
TI  - The Diabetic Foot Assessment.

PMID- 29369130
TI  - The Diabetic Foot Assessment.
AB  - The diabetic foot assessment is a key component in the care of a patient with
      diabetes. The assessment includes risk factor identification in both the diabetic
      patient's history and physical examination, foot care education, treatment, and
      referrals as needed. The foot complications related to diabetes such as
      peripheral neuropathy, foot ulceration, and amputation can be life altering. The
      American Diabetes Association recommends a diabetic foot examination annually for
      patients with diabetes with foot care education. Diabetic foot assessment may be
      recommended more frequently for individuals with risk factors contributing to
      ulceration, peripheral arterial disease, and peripheral neuropathy. This article
      reviews the diabetic foot assessment that nurses in healthcare settings and other
      healthcare professionals should use when caring for a diabetic patient.

PMID- 29369132
TI  - Development and Validity Testing of an Arthritis Self-Management Assessment Tool.
AB  - BACKGROUND: Because of the chronic, progressive nature of arthritis and the
      substantial effects it has on quality of life, patients may benefit from self
      management. However, no valid, reliable self-management assessment tool has been
      devised for patients with arthritis. PURPOSE: This study was conducted to develop
      a comprehensive self-management assessment tool for patients with arthritis, that
      is, the Arthritis Self-Management Assessment Tool (ASMAT). METHODS: To develop a
      list of qualified items corresponding to the conceptual definitions and
      attributes of arthritis self-management, a measurement model was established on
      the basis of theoretical and empirical foundations. Content validity testing was
      conducted to evaluate whether listed items were suitable for assessing arthritis
      self-management. Construct validity and reliability of the ASMAT were tested.
      Construct validity was examined using confirmatory factor analysis and
      nomological validity. RESULTS: The 32-item ASMAT was developed with a sample
      composed of patients in a clinic in South Korea. Content validity testing
      validated the 32 items, which comprised medical (10 items), behavioral (13
      items), and psychoemotional (9 items) management subscales. Construct validity
      testing of the ASMAT showed that the 32 items properly corresponded with
      conceptual constructs of arthritis self-management, and were suitable for
      assessing self-management ability in patients with arthritis. Reliability was
      also well supported. CONCLUSION: The ASMAT devised in the present study may aid
      the evaluation of patient self-management ability and the effectiveness of self
      management interventions. The authors believe the developed tool may also aid the
      identification of problems associated with the adoption of self-management
      practice, and thus improve symptom management, independence, and quality of life
      of patients with arthritis.

PMID- 29369133
TI  - A Systematic Integrative Review of Pin Site Crusts.
AB  - There continues to be a lack of knowledge in the overall management of pin site
      crusts for orthopaedic clinicians to make evidence-based decisions on their
      retention or removal. The goal of pin site care is to reduce, or where possible,
      prevent pin site infection. Understanding the role of pin site crusts in the
      management of the pin site and prevention of pin site infection is important. The
      aim of this systematic integrative review is to explore the effectiveness of pin
      site crusts as a biological dressing versus the removal of pin site crusts in pin
      site care and prevention of pin site infection. Three electronic databases were
      used to conduct a systematic search. The methodologies of five studies that met
      inclusion criteria were appraised using the Mixed Method appraisal Tool. Findings
      reveal that pin site crusts have similar properties to that of a dressing, as the
      crusts are able to act as a barrier between the insertion site of the pin and
      external environment, which can reduce infection. Additional high-quality
      evidence is required to solidify the effectiveness of pin site crusts as a
      biological dressing.

PMID- 29369134
TI  - Posttraumatic Stress, Depressive Emotions, and Satisfaction With Life After a
      Road Traffic Accident.
AB  - BACKGROUND: The psychological response of injured people after traffic accidents
      includes stress and depression. PURPOSE: To assess orthopaedic patients' stress,
      depression, and satisfaction with life after traffic accidents in Greece.
      METHODS: Descriptive, longitudinal, correlational study. Patients' background
      factors, injury severity, scores on the Impact of Events Scale-Revised (IES-R),
      the Center for Epidemiologic Studies Depression (CES-D) Scale, and the
      Satisfaction With Life Quality (SWLQ) Scale were recorded. The principles of the
      Declaration of Helsinki were applied. RESULTS: In total, 60 patients participated
      in this study during hospitalization following a road traffic accident and 40
      patients at 6 months after. Participants were mostly men (75%) with severe
      injuries (50%). The IES-R score at 6 months was significantly lower than during
      hospitalization. One out of 3 people had a CES-D score, which is considered of
      clinical significance. The SWLQ scores were considered high. CONCLUSION: As
      posttraumatic stress and depression seem to affect a considerable percentage of
      people involved in road traffic accidents in Greece, these individuals should be
      assessed for posttraumatic stress and depression while still hospitalized.

PMID- 29369136
TI  - Health Literacy, Health Disparities, and Sources of Health Information in U.S.
      Older Adults.

PMID- 29369135
TI  - Health Literacy, Health Disparities, and Sources of Health Information in U.S.
      Older Adults.
AB  - BACKGROUND: Low health literacy in older adults has been associated with poor
      health outcomes (i.e., mortality, decreased physical and cognitive functioning,
      and less preventive care utilization). Many factors associated with low health
      literacy are also associated with health disparities. Interaction with healthcare
      providers and sources of health information are influenced by an individual's
      health literacy and can impact health outcomes. PURPOSE: This study examined the
      relationships between health literacy, sources of health information, and
      demographic/background characteristics in older adults (aged 65 years and older)
      related to health literacy and disparities. METHODS: This descriptive,
      correlational study is a secondary analysis of the 2003 National Assessment of
      Adult Literacy, a large-scale national assessment. RESULTS: Older adults with
      lower health literacy have less income and education, rate their health as poor
      or fair, have visual or auditory difficulties, need help filling out forms,
      reading newspaper, or writing notes, and use each source of health information
      less (print and nonprint). Many of these characteristics and skills are
      predictive of health literacy and associated with health disparities. CONCLUSION:
      The results expand our knowledge of characteristics associated with health
      literacy and sources of health information used by older adults. Interventions to
      improve health outcomes including health disparities can focus on recognizing and
      meeting the health literacy demands of older adults.

PMID- 29369137
TI  - Lumbar Degenerative Disease With Intervertebral Disk Herniation.

PMID- 29369138
TI  - Lumbar Degenerative Disease With Intervertebral Disk Herniation.

PMID- 29369139
TI  - Simple Sling and Sling With Abductor Pillow: What's Wrong With These Pictures?

PMID- 29369140
TI  - New Certificants April 1-June 30, 2017.

PMID- 29369143
TI  - NAON Congress Program.

PMID- 29369142
TI  - New Certificants July 1-September 30, 2017.

PMID- 29369144
TI  - Familial clustering of hypertensive target organ damage in the community.
AB  - OBJECTIVES: Prior studies suggest that hypertensive target organ damage (TOD) is
      a heritable trait. However, the risk that parental TOD confers on propensity for
      TOD in their offspring, and how hypertensive TOD clusters in the context of
      parental versus offspring hypertension status remain unclear. METHODS: We studied
      3238 Framingham Heart Study participants (mean age 39 +/- 8 years, 53% women)
      with available parental data on TOD. Parents and offspring underwent measurements
      for left ventricular hypertrophy, increased relative wall thickness, albuminuria
      and conventional risk factors. RESULTS: Prevalence of any TOD (left ventricular
      hypertrophy or albuminuria) in participants with zero and at least one parents
      with any TOD was 7 and 13%, respectively (P < 0.001 for difference). Having at
      least one parent with TOD was associated with greater odds of TOD in offspring
      than individuals without parental TOD [multivariable-adjusted odds ratio (OR),
      1.65; 95% confidence interval (95% CI), 1.27-2.14]. Similarly, parental left
      ventricular hypertrophy was associated with offspring left ventricular
      hypertrophy (OR, 2.73; 95% CI 1.92-3.89), parental increased relative wall
      thickness conferred increased odds of increased relative wall thickness in the
      offspring (OR, 1.54; 95% CI 1.16-2.04) and parental albuminuria was related to
      offspring albuminuria (OR, 1.49; 95% CI 1.03-2.16). These associations remained
      significant upon adjustment for other risk factors, including blood pressure, and
      in analyses of subgroups defined according to parental or offspring hypertension
      status. CONCLUSION: Overall, our data suggest that familial clustering of TOD in
      the community is independent of blood pressure. Additional studies are warranted
      to confirm our observations.

PMID- 29369145
TI  - A system view and analysis of essential hypertension.
AB  - OBJECTIVES: The goal of this study was to investigate genes associated with
      essential hypertension from a system perspective, making use of bioinformatic
      tools to gain insights that are not evident when focusing at a detail-based
      resolution. METHODS: Using various databases (pathways, Genome Wide Association
      Studies, knockouts etc.), we compiled a set of about 200 genes that play a major
      role in hypertension and identified the interactions between them. This enabled
      us to create a protein-protein interaction network graph, from which we
      identified key elements, based on graph centrality analysis. Enriched gene
      regulatory elements (transcription factors and microRNAs) were extracted by motif
      finding techniques and knowledge-based tools. RESULTS: We found that the network
      is composed of modules associated with functions such as water retention,
      endothelial vasoconstriction, sympathetic activity and others. We identified the
      transcription factor SP1 and the two microRNAs miR27 (a and b) and miR548c-3p
      that seem to play a major role in regulating the network as they exert their
      control over several modules and are not restricted to specific functions. We
      also noticed that genes involved in metabolic diseases (e.g. insulin) are central
      to the network. CONCLUSION: We view the blood-pressure regulation mechanism as a
      system-of-systems, composed of several contributing subsystems and pathways
      rather than a single module. The system is regulated by distributed elements.
      Understanding this mode of action can lead to a more precise treatment and drug
      target discovery. Our analysis suggests that insulin plays a primary role in
      hypertension, highlighting the tight link between essential hypertension and
      diseases associated with the metabolic syndrome.

PMID- 29369146
TI  - Interaction between physical activity and television time on blood pressure
      level: cross-sectional data from 45 000 individuals.
AB  - OBJECTIVES: The aim was to investigate if there is an interaction between sitting
      time and leisure time physical activity on blood pressure and if there are age
      differences and sex differences in this respect. METHODS: Linear regression
      analysis on cross-sectional data was performed in more than 45 000 men and women
      from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45
      years). Self-reported leisure time physical activity was given in five levels
      from low (level 1) to vigorous physical activity (level 5) and television time
      was used as a proxy measure of sitting time. RESULTS: High physical activity was
      associated with lower DBP (P = 0.001), but not SBP. Active middle-aged men had
      lower DBP (-1.1 mmHg; 95% CI -1.7 to -0.4) compared with inactive participants.
      Prolonged television time was associated with higher SBP (P < 0.001) and DBP (P =
      0.011) in both sexes and in most age groups. Watching 3 h instead of 1 h
      television per day was associated with higher SBP in middle-aged women (SBP: 1.1
      mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2 mmHg; 95% CI 0.8-1.6). Only in young men,
      a high physical activity (level 4 instead of level 1) could compensate for a
      prolonged television time (3 h per day) in terms of DBP. CONCLUSION: Prolonged
      television time was associated with higher SBP and DBP in both sexes and at most
      ages, whereas an increased physical activity was mainly associated with a lower
      DBP. Only in young men, a high physical activity could compensate for prolonged
      television time regarding DBP.

PMID- 29369147
TI  - Target home morning SBP be below 125 mmHg in type 2 diabetes patients.
AB  - BACKGROUND: It is not established to what extent self-monitoring of home BP be
      lowered in patients with type 2 diabetes. We tested the hypothesis that the
      appropriate home morning SBP cutoff value is 125 mmHg in our stratification of
      cardiovascular risk in type 2 diabetes. METHOD: Clinic and home BP monitoring
      were performed in 4308 individuals (1057 people with diabetes and 3251,
      nondiabetes), and we tested two cutoff values of home morning SBP (MSBP): 135 and
      125 mmHg. Multivariable Cox regression analyses adjusting for age, sex, body mass
      index, history of cardiovascular events, presence of chronic kidney disease, and
      atrial fibrillation were used for incident cardiovascular events. Main outcomes
      included stroke, myocardial infarction, sudden death, and acute aortic
      dissection. RESULTS: A Kaplan-Meyer analysis revealed that MSBP at least 135 mmHg
      was significantly associated with cardiovascular events in both diabetes and
      nondiabetes groups (log-rank test, both P < 0.01), whereas MSBP at least 125 mmHg
      was significantly associated with cardiovascular events in the diabetes group (P
      = 0.012) but not nondiabetes group. In a multivariable analysis, home MSBP at
      least 135 mmHg was significantly associated with cardiovascular events in the
      diabetes group [hazard ratio 2.45, 95% confidence interval (CI) 1.17-5.14, P =
      0.017) and nondiabetes group (hazard ratio 1.79, 95% CI 1.08-2.97, P = 0.024).
      Home MSBP at least 125 mmHg was an independent predictor of cardiovascular events
      in the diabetes group (hazard ratio 4.35, 95% CI 1.04-18.25, P = 0.045) but not
      in the nondiabetes group. CONCLUSION: In patients with type 2 diabetes, the 125
      mmHg cutoff value for home MSBP would be the appropriate cutoff value in
      predicting combined cardiovascular outcomes.

PMID- 29369148
TI  - Focus on diagnostic and therapeutic aspects of hypertension.

PMID- 29369149
TI  - Age of Infection with Kaposi Sarcoma-Associated Herpesvirus and Subsequent
      Antibody Values Among Children in Uganda.
AB  - We investigated associations between Kaposi sarcoma-associated herpesvirus (KSHV)
      seroconversion age and KSHV antibody values in Ugandan children. Every annual
      delay in KSHV seroconversion age was associated with a reduction of 19% (P <
      0.0001) in K8.1 and 27% (P < 0.0001) in ORF73 antibody values at 6 years of age.
      Early infection may be an important risk factor for KSHV pathogenesis and viral
      shedding in saliva, leading to transmission.

PMID- 29369150
TI  - Improving Outcomes of Posterior Approach Levatorpexy for Congenital Ptosis With
      Reduced Levator Function.
AB  - PURPOSE: The authors present a new series of our experience using posterior
      approach levatorpexy for congenital ptosis with poorer levator function (LF) in
      comparison with our first published report. This technique avoids a skin incision
      or any resection in addition to no excision of tissue. METHODS: A consecutive
      series of 16 patients. Retrospective review of levatorpexy for congenital ptosis.
      Data included eyelid margin reflex distance 1, pretarsal show, contour, and
      complications, including nocturnal lagophthalmos, eyelid lag on downgaze, and dry
      eye. Surgery was considered successful if the following 4 criteria were
      simultaneously met: a postoperative margin reflex distance 1 of >=2 mm and <=4.5
      mm, intereyelid height asymmetry of <=1 mm, no overcorrection compare to opposite
      eye, and satisfactory eyelid contour. RESULTS: Mean age was 10.3 years (range 1
      26 years). Mean LF was 7.3 mm (2-14 mm), while 66% (12) had LF <=7 mm.
      Preoperative phenylephrine test was positive in 87.5% of patients. Mean
      preoperative and postoperative margin reflex distance 1 was 1.34 mm and 3.2 mm,
      respectively. Fourteen patients (87%) achieved the desired eyelid height and
      fulfilled our criteria set of success. Among 10 patients with LF <=7 mm, 9 (90%)
      achieved the desired eyelid height and fulfilled our criteria set of success.
      Ninety-four percent did not report nocturnal lagophthalmos. Three patients needed
      a further levatorpexy procedure due to undercorrection. Mean postoperative follow
      up was up 11.2 (range 6-36) months. CONCLUSIONS: Posterior approach levatorpexy
      is an useful first-line choice for congenital ptosis for all ranges of LF. It is
      popular among parents due to its avoidance of a skin incision or any resection or
      excision of tissue.

PMID- 29369151
TI  - Autologous Fat Graft for the Treatment of Sighted Posttraumatic Enophthalmos and
      Sunken Upper Eyelid.
AB  - PURPOSE: The treatment of enophthalmos and sunken upper eyelid is challenging.
      Although autologous fat graft has been widely used in breast augmentation,
      buttock contouring, and facial rejuvenation, its application in enophthalmos and
      sunken upper eyelid is not yet widely utilized. The clinical safety and value of
      autologous fat graft in sighted patients with enophthalmos and sunken upper
      eyelid are unclear. This study retrospectively analyzed the cosmetic results and
      safety of autologous fat graft in the correction of sighted traumatic
      enophthalmos and sunken upper eyelid. METHODS: Autologous fat graft was performed
      in 9 patients with posttraumatic enophthalmos and sunken upper eyelid. The visual
      acuity, orbital swelling, eye movement, enophthalmos, and sunken upper eyelid
      were observed. RESULTS: Eight to 24 months after autologous fat graft,
      enophthalmos and sunken upper eyelid in 9 patients improved significantly.
      Although orbital swelling occurred in the early postoperative period, no vision
      loss, eye movement limitation, or fat embolism had occurred. CONCLUSION:
      Autologous fat graft is an effective, predictable, scarless, and minimally
      invasive surgery for the correction of the sighted posttraumatic enophthalmos and
      sunken upper eyelid. The possible risk of fat embolization and blindness from the
      compression of the optic nerve should not be neglected. Further studies and more
      cases must be performed.

PMID- 29369152
TI  - Paracanthal "One-Snip" Decompression in a Cadaver Model of Retrobulbar
      Hemorrhage.
AB  - PURPOSE: The authors assess the effectiveness of a modified paracanthal or "one
      snip" procedure compared with the traditional lateral canthotomy and inferior
      cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a
      human cadaveric model of retrobulbar hemorrhage. METHODS: This study comprised a
      comparative interventional study in a cadaveric model of retrobulbar hemorrhage.
      Six orbits of 3 fresh cadavers were included in the study. Baseline measurements
      of IOP and proptosis were recorded for all 6 orbits before and after simulation
      of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent
      traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3)
      underwent modified paracanthal or "one-snip" procedure. The primary outcome
      measures were reduction in IOP and proptosis between the 2 techniques. RESULTS:
      Following lateral canthotomy and inferior cantholysis of each right orbit, the
      average IOP dropped to 14 mm Hg (range of 11-18 mm Hg), corresponding to a mean
      decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the
      average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to
      a mean decrease of 22 mm Hg. There was no statistically significant difference in
      IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2
      treatment groups. CONCLUSIONS: Compared with traditional lateral canthotomy xand
      inferior cantholysis, the modified paracanthal or "one-snip" procedure is
      effective for IOP reduction and led to mild improvement of proptosis in a
      cadaveric model of retrobulbar hemorrhage. The authors hope this study helps
      improve orbital compartment syndrome outcomes by providing an option that more
      providers will feel comfortable performing and therefore decreasing time to
      surgical decompression.

PMID- 29369153
TI  - Deep Orbital Sub-Q Hyaluronic Acid Filler Injection for Enophthalmic Sighted Eyes
      in Parry-Romberg Syndrome.
AB  - PURPOSE: The authors present a consecutive series of deep orbital Sub-Q
      injections to treat enophthalmic sighted eyes in Parry-Romberg syndrome patients.
      METHODS: Retrospective, interventional case series in 2 centers. Data were
      collected on patient demographics, Parry-Romberg syndrome onset age, previous
      orbital and eyelid surgeries, diplopia, ocular movement restriction before and
      after the injection, number of injections, interval between injections,
      indication for any top-up or dissolution of filler, and any other complications.
      In all cases, the hyaluronic acid gel used was Restylane Sub-Q + Lidocaine.
      RESULTS: A total of 8 injections on 3 patients with Parry-Romberg syndrome, and
      significant enophthalmos is reported. All injections were with deep orbital Sub-Q
      filler. All patients were females, aged 32, 24, and 52 years old while their
      symptoms started at 15, 16, and 30 years old, respectively. None had orbital
      surgery prior to the injection. Follow up period was 2, 7, and 5 years
      respectively. All presented a significant enophthalmos of 4 mm which reduced to 1
      mm after the injection, and duration effect was 18, 24, and 20 months,
      respectively. We observed a significant improvement in enophthalmos,
      lagophthalmos, exposure keratopathy, and even ocular motility. Lagophthalmos
      improved from 1, 4, and 7 mm to 0, 1, and 2 mm post injection. Ocular motility
      improved with no onset of new limitation or diplopia. Lower eyelid retraction
      increased in 1 patient after orbital injection. No other complications occurred.
      CONCLUSIONS: Deep orbital Sub-Q hyaluronic injection for treatment of
      enophthalmos in Parry-Romberg syndrome is an useful option in sighted eyes.

PMID- 29369154
TI  - Combining Bilateral Magnetically Controlled Implants Inserted Parallel to the
      Spine With Rib to Pelvis Fixation: Surgical Technique and Early Results.
AB  - Spine-based fixation of magnetically controlled lengthening devices has been
      successfully performed for children with early-onset scoliosis. However, spinal
      manipulation may lead to ossifications, stiffness, and autofusion as previously
      described. To avoid these problems, a surgical technique combining bilateral
      externally controlled magnetic device implantation with a rib cradle and pelvic
      hook fixation was introduced by us in 2011. By using a bilateral single-rib or
      double-rib cradle fixation and a pelvic hook, the magnetic device is
      percutaneously inserted. The spine corrects indirectly without further
      manipulation. In small rib diameter or severe osteoporosis, double-rib cradles
      are used. Our introduced technique enables modification of the rib vertebral
      angle, which may be beneficial in children with spinal muscular atrophy and rib
      cage deformity. This nonrandomized prospective study describes 18 children with
      neuromuscular scoliosis treated first by this method. All patients followed the
      same protocol, with expansion procedures being performed 5 months after surgery
      and every 3 months thereafter. Clinical, radiologic, and complication data were
      analyzed, showing a significant reduction in scoliosis and pelvic obliquity and
      an increase in spinal length, which could be maintained over a follow-up period
      of 1.2 years. The overall complication rate was lower than previously described,
      with 8%, 2 of them requiring surgery.

PMID- 29369155
TI  - Distribution and Determinants of 90-Day Payments for Multilevel Posterior Lumbar
      Fusion: A Medicare Analysis.
AB  - STUDY DESIGN: A retrospective, economic analysis. OBJECTIVE: The objective of
      this article is to analyze the distribution of 90-day payments, sources of
      variation, and reimbursement for complications and readmissions for primary >=3
      level posterior lumbar fusion (PLF) from Medicare data. A secondary objective was
      to identify risk factors for complications. SUMMARY OF BACKGROUND DATA: Bundled
      payments represent a single payment system to cover all costs associated with a
      single episode of care, typically over 90 days. The dollar amount spent on
      different health service providers and the variation in payments for >=3-level
      PLF have not been analyzed from a bundled perspective. MATERIALS AND METHODS:
      Administrative claims data were used to study 90-day Medicare (2005-2012)
      reimbursements for primary >=3-level PLF for deformity and degenerative
      conditions of the lumbar spine. Distribution of payments, sources of variation,
      and reimbursements for managing complications were studied using linear
      regression models. Risk factors for complications were studied by stepwise
      multiple-variable logistic regression analysis. RESULTS: Hospital payments
      comprised 73.8% share of total 90-day payment. Adjusted analysis identified
      several factors for variation in index hospital payments. The average 90-day
      Medicare payment for all multilevel PLFs without complications was $35,878 per
      patient. The additional average cost of treating complications with/without
      revision surgery within 90 days period ranged from $17,284 to $68,963. A 90-day
      bundle for >=3-level PLF with readmission ranges from $88,648 (3 levels) to
      $117,215 (8+ levels). Rates and risk factors for complications were also
      identified. CONCLUSIONS: The average 90-day payment per patient from Medicare was
      $35,878 with several factors such as levels of surgery, comorbidities, and
      development of complications influencing the cost. The study also identifies the
      risks and costs associated with complications and readmissions and emphasize the
      significant effect these would have on bundled payments (additional burden of up
      to 192% the cost of an average uncomplicated procedure over 90 days). LEVEL OF
      EVIDENCE: Level 3.

PMID- 29369156
TI  - Hepatitis C virus cure does not impact kidney function decline in HIV co-infected
      patients.
AB  - OBJECTIVE: To examine the impact of sustained virologic response (SVR) and
      illicit (injection and noninjection) drug use on kidney function among hepatitis
      C virus (HCV) and HIV co-infected individuals. DESIGN: Longitudinal observational
      cohort study of HCV-HIV co-infected patients. METHODS: Data from 1631 patients
      enrolled in the Canadian Co-Infection Cohort between 2003 and 2016 were analyzed.
      Patients who achieved SVR were matched 1 : 2 with chronically infected patients
      using time-dependent propensity scores. Linear regression with generalized
      estimating equations was used to model differences in estimated glomerular
      filtration rates (eGFR) between chronic HCV-infected patients and those achieving
      SVR. The relationship between illicit drug use and eGFR was explored in patients
      who achieved SVR. RESULTS: We identified 384 co-infected patients who achieved
      SVR (53% treated with interferon-free antiviral regimens) and 768 propensity
      score matched patients with chronic HCV infection. Most patients were men (78%)
      and white (87%), with a median age of 51 years (interquartile range: 45-56).
      During 1767 person-years of follow-up, 4041 eGFR measurements were available for
      analysis. Annual rates of decline in eGFR were similar between patients with SVR
      [-1.32 (ml/min per 1.73 m)/year, 95% confidence interval (CI) -1.75 to -0.90] and
      chronic infection [-1.19 (ml/min per 1.73 m) per year, 95% CI -1.55 to -0.84].
      Among SVR patients, recent injection cocaine use was associated with rapid eGFR
      decline [-2.16 (ml/min per 1.73 m)/year, 95% CI -4.17 to -0.16]. CONCLUSION: SVR
      did not reduce the rate of kidney function decline among HCV-HIV co-infected
      patients. Increased risk of chronic kidney disease in co-infection may not be
      related to persistent HCV replication but to ongoing injection cocaine use.

PMID- 29369157
TI  - HIV reservoir dynamics in HAART-treated poor immunological responder patients
      under IL-7 therapy.
AB  - OBJECTIVES: Recombinant Human IL-7 (rhIL-7) therapy allows reconstituting
      systemic and tissue-associated CD4 T-cell populations in HIV-infected poor
      immunological responder (PIR) patients. However, in-vitro studies suggest that
      the impact of rhIL-7 treatment on HIV-DNA loads in vivo remains questionable.
      DESIGN: We assessed the dynamics of circulating HIV-DNA loads in IL-7-treated HIV
      infected PIR individuals. METHODS: Forty-one rhIL-7-treated and 16 control
      participants from the INSPIRE-3 clinical trial were included. Participants
      received three weekly subcutaneous injections of rhIL-7. HIV-DNA was quantified
      by nested quantitative PCR in white blood cells sampled at D0, D28 and M3 and
      expressed as per milliliters and per CD4 T-cell. Changes in HIV-DNA loads in the
      CD4 compartment at M3 were confirmed on sorted CD4 cells. RESULTS: Together with
      rhIL-7-induced T-cell expansion, we observed a significant raise in both infected
      cell frequencies and counts during the first 28 days of follow-up. During this
      period, HIV-DNA load per CD4 T-cell also increased, to a lower extent. Three
      months post-therapy, both the frequencies and counts of infected cells diminished
      in blood as compared with D28 but remained significantly higher than before IL-7
      therapy. In contrast, infection frequencies strongly diminished within CD4 cells,
      reaching slightly but significantly lower levels than at baseline. CONCLUSION:
      rhIL-7 treatment initially drives an expansion of HIV reservoir in PIR patients
      by D28. This expansion is probably not only because of infected cell
      proliferation, but also to possible enhanced neoinfection, despite highly active
      antiretroviral therapy. In contrast, subsequent reduction in HIV-DNA load per CD4
      T-cell argues for partial elimination of infected cells between D28 and M3.

PMID- 29369158
TI  - The growing burden of noncommunicable disease among persons living with HIV in
      Zimbabwe.
AB  - OBJECTIVES: We aim to characterize the future noncommunicable disease (NCD)
      burden in Zimbabwe to identify future health system priorities. METHODS: We
      developed an individual-based multidisease model for Zimbabwe, simulating births,
      deaths, infection with HIV and progression and key NCD [asthma, chronic kidney
      disease (CKD), depression, diabetes, hypertension, stroke, breast, cervical,
      colorectal, liver, oesophageal, prostate and all other cancers]. The model was
      parameterized using national and regional surveillance and epidemiological data.
      Demographic and NCD burden projections were generated for 2015 to 2035. RESULTS:
      The model predicts that mean age of PLHIV will increase from 31 to 45 years
      between 2015 and 2035 (compared with 20-26 in uninfected individuals).
      Consequently, the proportion suffering from at least one key NCD in 2035 will
      increase by 26% in PLHIV and 6% in uninfected. Adult PLHIV will be twice as
      likely to suffer from at least one key NCD in 2035 compared with uninfected
      adults; with 15.2% of all key NCDs diagnosed in adult PLHIV, whereas contributing
      only 5% of the Zimbabwean population. The most prevalent NCDs will be
      hypertension, CKD, depression and cancers. This demographic and disease shift in
      PLHIV is mainly because of reductions in incidence and the success of ART scale
      up leading to longer life expectancy, and to a lesser extent, the cumulative
      exposure to HIV and ART. CONCLUSION: NCD services will need to be expanded in
      Zimbabwe. They will need to be integrated into HIV care programmes, although the
      growing NCD burden amongst uninfected individuals presenting opportunities for
      additional services developed within HIV care to benefit HIV-negative persons.

PMID- 29369159
TI  - Substance-associated elevations in monocyte activation among methamphetamine
      users with treated HIV infection.
AB  - OBJECTIVE: Microbial translocation and monocyte activation predict mortality in
      treated HIV. We examined whether substance use independently contributes to these
      pathophysiologic processes. DESIGN: Cross-sectional study at baseline for a
      randomized controlled trial. METHODS: HIV-positive, methamphetamine-using MSM
      with undetectable HIV viral load (less than 40 copies/ml) were enrolled. We
      examined if plasma biomarkers of monocyte activation and intestinal barrier
      integrity were associated with the following: reactive urine toxicology results
      (Tox+) for stimulants (i.e., methamphetamine or cocaine) and substance use
      severity measured by the Addiction Severity Index. Multiple linear regression
      models adjusted for age, antiretroviral therapy regimen, CD4 T-cell count,
      interleukin-6, and alcohol use severity. RESULTS: The sample of 84 virally
      suppressed MSM had a median CD4 T-cell count of 645 cells/MUl. Those who were
      Tox+ for stimulants displayed higher soluble CD14 (sCD14) levels (2087 versus
      1801 ng/ml; P = 0.009), and this difference remained significant after adjusting
      for covariates (standardized beta = 0.23, P = 0.026). Greater substance use
      severity was also independently associated with higher sCD14 after adjusting for
      covariates (standardized beta = 0.29, P = 0.013). Being Tox+ for stimulants and
      substance use severity were not associated with soluble CD163 (sCD163) or
      intestinal fatty acid binding protein (iFABP) levels (P > 0.05). CONCLUSIONS:
      Monocyte activation is one plausible mechanism by which stimulant use may
      increase clinical HIV progression.

PMID- 29369160
TI  - HLA-associated polymorphisms in the HIV-2 capsid highlight key differences
      between HIV-1 and HIV-2 immune adaptation.
AB  - OBJECTIVE: HIV-1 frequently adapts in response to immune pressure from cytotoxic
      T-lymphocytes (CTL). Many HIV-2 infected individuals have robust capsid-specific
      CTL responses associated with viral control. Despite this CTL pressure, adaptive
      changes in this key immunogenic HIV-2 protein have not previously been described.
      We sought to compare selective pressure on HIV-1 and HIV-2 capsids and identify
      HLA-associated viral polymorphisms in HIV-2. DESIGN AND METHODS: Bioinformatic
      algorithms to identify sites under positive and negative selective pressure and a
      statistical model of evolution to identify HLA-associated polymorphisms in HIV-2
      was applied to sequences from a community cohort in Guinea-Bissau. IFN-gamma
      ELISpots were used to compare T-cell responses to wild-type and variant epitopes.
      RESULTS: We identified greater purifying selection and less sites under positive
      selective pressure in HIV-2 compared with HIV-1. Five HIV-2 codons with HLA
      associated polymorphisms were detected all within or around known or predicted
      CTL epitopes. One site was within the HLA-B58 SuperType (ST)-restricted epitope
      (TSTVEEQIQW), the HIV-2 equivalent of the HIV-1 TW10 epitope. In contrast to HIV
      1, where a T->N mutation at position 3 is associated with resulting loss of CTL
      control, an E->D mutation at position 5 was observed in HIV-2. Robust CTL
      responses to the variant HIV-2 epitope were seen, suggesting that HIV-2
      adaptation may be at the level of T-cell receptor recognition. CONCLUSION:
      Greater constraints on evolution may exist in HIV-2, resulting in more purifying
      selection and different immune adaptation pathways in HIV-1 and HIV-2 capsids.
      This may allow CTL responses to persist in HIV-2.

PMID- 29369162
TI  - Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV.
AB  - OBJECTIVE: To evaluate dolutegravir pharmacokinetics during pregnancy compared
      with postpartum and in infant washout samples after delivery. DESIGN: Ongoing,
      nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study
      of antiretroviral pharmacokinetics in HIV-infected pregnant women and infants.
      METHODS: Intensive steady-state 24 h pharmacokinetic profiles after dolutegravir
      50 mg once-daily were performed during the second trimester (2T), third trimester
      (3T) and postpartum. Maternal delivery and postnatal infant samples were
      collected after birth. Dolutegravir was measured by validated LC-MS/MS;
      quantitation limit was 0.005 MUg/ml. A two-tailed Wilcoxon signed-rank test
      (alpha = 0.10) was employed for paired within-subject comparisons. RESULTS:
      Twenty-nine enrolled participants had a median age of 32 years (range 21-42).
      Pharmacokinetic data were available for 15 (2T), 28 (3T) and 23 (postpartum)
      women. Median dolutegravir AUC0-24,Cmax and C24 were 25-51% lower in the 2T and
      3T compared with postpartum. The median cord blood/maternal plasma concentration
      ratio was 1.25 (n = 18). In 21 infants, median elimination half-life was 32.8 h
      after in utero exposure. Viral load at delivery was less than 50 copies/ml for
      27/29 women (93%). Twenty-nine infants were HIV-negative. Renal abnormalities
      noted on ultrasound in two infants were deemed possibly related to dolutegravir.
      CONCLUSION: Dolutegravir exposure is lower in pregnancy compared with postpartum
      in the same women on once-daily dosing. Median AUC0-24 during pregnancy was
      similar to, whereas trough concentrations were lower than, those seen in
      nonpregnant adults. Trough concentrations in pregnancy were well above
      dolutegravir EC90 (0.064 MUg/ml). Dolutegravir readily crosses the placenta.
      Infant elimination is prolonged, with half-life over twice that of historical
      adult controls.

PMID- 29369163
TI  - The influence of human leukocyte antigen-types on disease progression among HIV-2
      infected patients in Guinea-Bissau.
AB  - OBJECTIVES: HIV-2 is endemic in West Africa and is characterized by lower
      transmissibility because of lower viral load, and HIV-2-infected persons usually
      have a slower progression to AIDS. The mechanisms behind the slower disease
      progression are unknown. The main objective was to identify specific HLA class I
      and II alleles that may influence the disease progression of HIV-2 infection.
      DESIGN: Cohort follow-up study. METHODS: We used high-resolution HLA typing of
      DNA from 437 antiretroviral naive HIV-2-infected patients from the Bissau HIV
      Cohort, Guinea-Bissau, to identify HLA alleles with an influence on HIV-2 disease
      progression. The effect of HLA-type on viral load and CD4 cell count was assessed
      initially by ranksum-test and t-test, followed by adjusted logistic regression
      and multivariable linear regression analysis, respectively. RESULTS: Three
      alleles (HLA-B58:01, HLA-DPB110:01 and HLA-DRB111:01) were associated with lower
      possibility of detectable baseline plasma viral load (P = 0.002, P = 0.044 and P
      = 0.033, respectively), and no alleles were associated with higher possibility of
      detectable plasma viral load. HLA-DPB110:01 and HLA-DRB111:01 were in linkage
      disequilibrium (P = 0.047). Patients with heterozygous HLA types in all their HLA
      class I loci or in one or two loci were not more likely to have undetectable
      viral load compared with patients that were homozygous in all their class I loci
      after adjusting for sex and CD4 cell count (P = 0.93 and P = 0.88, respectively).
      CONCLUSION: The three alleles HLA-B58:01, HLA-DPB110:01 and HLA-DRB111:01 may
      protect against HIV-2 disease progression towards AIDS.

PMID- 29369164
TI  - Individual and community-level risk factors for HIV stigma in 21 Zambian and
      South African communities: analysis of data from the HPTN071 (PopART) study.
AB  - OBJECTIVE: To describe the prevalence and determinants of HIV stigma in 21
      communities in Zambia and South Africa. DESIGN: Analysis of baseline data from
      the HPTN 071 (PopART) cluster-randomized trial. HIV stigma data came from a
      random sample of 3859 people living with HIV. Community-level exposures
      reflecting HIV fears and judgements and perceptions of HIV stigma came from a
      random sample of community members not living with HIV (n = 5088), and from
      health workers (HW) (n = 851). METHODS: We calculated the prevalence of
      internalized stigma, and stigma experienced in the community or in a healthcare
      setting in the past year. We conducted risk-factor analyses using logistic
      regression, adjusting for clustering. RESULTS: Internalized stigma (868/3859,
      prevalence 22.5%) was not associated with sociodemographic characteristics but
      was less common among those with a longer period since diagnosis (P = 0.043).
      Stigma experienced in the community (853/3859, 22.1%) was more common among women
      (P = 0.016), older (P = 0.011) and unmarried (P = 0.009) individuals, those who
      had disclosed to others (P < 0.001), and those with more lifetime sexual partners
      (P < 0.001). Stigma experienced in a healthcare setting (280/3859, 7.3%) was more
      common among women (P = 0.019) and those reporting more lifetime sexual partners
      (P = 0.001) and higher wealth (P = 0.003). Experienced stigma was more common in
      clusters wherever community members perceived higher levels of stigma, but was
      not associated with the beliefs of community members or HW. CONCLUSION: HIV
      stigma remains unacceptably high in South Africa and Zambia and may act as
      barrier to HIV prevention and treatment. Further research is needed to understand
      its determinants.

PMID- 29369165
TI  - IL-7 treatment supports CD8+ MAIT cell restoration in HIV-1 infected patients on
      ART.
AB  - : Chronic HIV-1 infection is associated with lower frequencies and functional
      impairment of mucosa-associated invariant T (MAIT) cells. We evaluated IL-7
      treatment to restore MAIT cells in peripheral blood of chronically HIV-1 infected
      individuals on ART. IL-7 led to increased relative and absolute levels of MAIT
      cells and this expansion occurred primarily in the CD8+ subset. These results
      suggest that IL-7 may represent a therapeutic intervention for the restoration of
      MAIT cells in chronic HIV-1 infection.

PMID- 29369166
TI  - Novel mediators of statin effects on plaque in HIV: a proteomics approach.
AB  - OBJECTIVE: HIV patients have increased atherosclerotic coronary vascular disease
      (ASCVD), thought to be mediated through inflammatory mechanisms. We hypothesized
      that among asymptomatic HIV-infected patients with subclinical coronary plaque,
      statin therapy would modulate unique inflammatory and cardiovascular proteins in
      relation to change in subclinical coronary plaque volume. We tested this
      hypothesis using a novel proteomics approach. DESIGN: Forty HIV-infected
      participants were randomized to atorvastatin (40 mg/day) versus placebo, and
      underwent computed tomography coronary angiography to quantify plaque volume at
      baseline and 1 year. METHODS: We used Olink Cardiovascular III and
      Cardiometabolic panels based on dual antibody epitope recognition with linked DNA
      amplification to compare change over time in 184 proteins in treatment versus
      placebo and in relation to change in coronary plaque volume. RESULTS: Six
      proteins (TFPI, CCL24, NT-Pro BNP, MBL2, LTBR, PCOLCE) changed significantly in
      the atorvastatin versus placebo group, many in innate immune and other novel
      inflammatory pathways. Twenty-six proteins changed significantly in relationship
      to total coronary plaque volume over 1 year. Notably, many of these proteins
      changed only weakly in relationship to change in low-density lipoprotein (LDL).
      Overlapping these two broad discovery approaches, proteins involved in myocardial
      fibrosis/collagen formation and monocyte chemoattraction changed with statin
      treatment, in relationship to plaque volume, but not LDL. CONCLUSION: This proof
      of-concept study employing a proteomic discovery platform offers insight into
      statin effects on novel immune pathways relevant to ASCVD progression in HIV.
      Novel biomarker discovery may enhance precision medicine strategies to estimate
      the efficacy of targeted therapies to reduce ASCVD progression and events in HIV.

PMID- 29369168
TI  - A case report of metastatic hepatocellular carcinoma in the mandible and coracoid
      process: A rare presentation.
AB  - RATIONALE: We report a rare case of hepatocellular carcinoma (HCC) with
      metastases to the mandible and coracoid process of scapula without evidence of
      lung involvement. PATIENTS CONCERNS: The patient was diagnosed with HCC,
      presented 5 months later with right lower tooth pain, swelling over the right
      mandible area and right shoulder pain. DIAGNOSES: Histopathological examination
      of mandible showed findings suggestive of metastatic HCC. Magnetic resonance
      imaging (MRI) of the right shoulder revealed findings of irregular enhancing
      lesion at the right coracoid process causing erosion of the coracoid process.
      INTERVENTIONS: Patient was subsequently referred for palliative medicine care.
      OUTCOMES: He received adequate analgesia. LESSONS: Oral cavity and scapula
      metastases from HCC are very rare. Most oral metastases are associated with lung
      metastases, and they possibly occur by hematogenous route. In our case, the
      possible pathway of metastasis is an anastomotic network of paravertebral veins
      that bypasses the pulmonary, inferior caval, and portal venous circulations.

PMID- 29369167
TI  - HIV viral suppression and geospatial patterns of HIV antiretroviral therapy
      treatment facility use in Rakai, Uganda.
AB  - OBJECTIVE: To assess geospatial patterns of HIV antiretroviral therapy (ART)
      treatment facility use and whether they were impacted by viral load suppression.
      METHODS: We extracted data on the location and type of care services utilized by
      HIV-positive persons accessing ART between February 2015 and September 2016 from
      the Rakai Community Cohort Study in Uganda. The distance from Rakai Community
      Cohort Study households to facilities offering ART was calculated using the open
      street map road network. Modified Poisson regression was used to identify
      predictors of distance traveled and, for those traveling beyond their nearest
      facility, the probability of accessing services from a tertiary care facility.
      RESULTS: In total, 1554 HIV-positive participants were identified, of whom 68%
      had initiated ART. The median distance from households to the nearest ART
      facility was 3.10 km (interquartile range, 1.65-5.05), but the median distance
      traveled was 5.26 km (interquartile range, 3.00-10.03, P < 0.001) and 57% of
      individuals travelled further than their nearest facility for ART. Those with
      higher education and wealth were more likely to travel further. In total, 93% of
      persons on ART were virally suppressed, and there was no difference in the
      distance traveled to an ART facility between those with suppressed and
      unsuppressed viral loads (5.26 vs. 5.27 km, P = 0.650). CONCLUSION: Distance
      traveled to HIV clinics was increased with higher socioeconomic status,
      suggesting that wealthier individuals exercise greater choice. However, distance
      traveled did not vary by those who were or were not virally suppressed.

PMID- 29369169
TI  - Primary spinal mucosa-associated lymphoid tissue lymphoma: A case report.
AB  - RATIONALE: Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent B
      cell lymphoma which occurs mainly in the organs having mucosal layer and owns a
      fairly good prognosis. To date, 7 cases of spinal primary MALT has been reported
      before. However, there is no consensus on the optimal adjuvant treatment
      modalities for primary spinal MALT. The aim of this study was to add a new case
      of MALT which responded well to systemic therapy to the literature and to review
      the current literature. PATIENT CONCERNS: A 68-year-old woman visited to our
      hospital due to back pain and progressive bilateral lower extremity weakness for
      2 months. Magnetic resonance imaging (MRI) of the spine revealed a diffusely
      contrast-enhancing epidural mass extending from vertebral body T6 to T8 with
      compression of the spinal cord. Due to the spinal cord compression, patient
      underwent surgical resection. Histological examination indicated monocytoid small
      B-cells. Immunochemical study demonstrates that most tumor cells were positive
      for CD20, CD21, CD45, CD79a, CD43, bcl-2 with Ki-67 labing index was 15%, but
      were negative for CD3, CD5 cyclin D1, BCL6, and CD23. The positron emission
      tomography/computer tomography (PET/CT) revealed that right iliac wing and right
      liver were metastases for the standard uptake value (SUV) were 9.05 and 8.35,
      respectively. DIAGNOSES: Based on these findings, final diagnosis of spinal MALT
      lymphoma was made. INTERVENTIONS: After the diagnosis, the patient received 6
      cycles of immuno-chemotherapy and repeated intrathecal methotrexate and
      intrathecal cytarabine. OUTCOMES: At 1 year follow up, no recurrence or other
      dissemination was detected. LESSONS: Chemotherapy and/or radiation have been
      employed in larger case series. While there is no defined treatment guideline for
      this rare disease entity, our reported case suggests a favorable prognosis when
      combining both surgical and adjuvant systemic approach.

PMID- 29369170
TI  - Five-year serial follow-up of muscle MRI in adult onset myotonic dystrophy type
      1: A case report.
AB  - RATIONALE: Although several studies have described the involvement pattern of
      myotonic dystrophy type 1 (DM1) using muscle MRI, most of these studies have
      limitations as cross-sectional studies. To the best of our knowledge, there have
      been no reports of longitudinal studies describing muscle involvement patterns in
      patients with DM1 via serial MRI. PATIENT CONCERNS: Progressive weakness of both
      lower extremities. DIAGNOSIS: Two patients with DM1. INTERVENTION: The serial
      muscle MRI performed in the 2 patients with DM1. OUTCOMES: The serial muscle MRI
      showed early involvement of proximal (tensor fascia latae) and truncal muscles
      (spine extensor muscles), and these longitudinal imaging may be helpful to reveal
      the pattern of muscle involvement in patients with DM1. LESSONS: Since most
      previous studies on muscle involvement patterns in DM1 patients were cross
      sectional studies, this case series of studying muscle involvement patterns
      through serial MRI in patients with DM1 may have significant clinical
      significance.

PMID- 29369171
TI  - Microdissected thin anterolateral thigh perforator flaps with multiple
      perforators: A series of case reports.
AB  - INTRODUCTION: The study aimed to explore the effect of microdissected thin
      anterolateral thigh (MTALT) perforator flap with multiple perforators on patients
      with complex defects on the hand, elbow, heel, or knee. METHODS: From March 2012
      to February 2013, 5 patients with complex defects on the hand, elbow, heel, or
      knee were included. During the flap preparation, 2 to 3 perforators penetrating
      the fascia of the anterolateral femoral area were initially detected, and the
      deep fascia was incised. The superficial fascia layer of the flap and the deep
      adipose were then dissected, and removed after verifying the distribution of the
      blood vessels using an operating microscope. The whole flap was then elevated,
      and transposed to the recipient areas for microsurgical reparation. RESULTS: Two
      cases of post-burn scar contracture and 3 cases of traumatic tissue defects were
      successfully reconstructed with these multiple-perforator MTALT flaps. No
      complication was reported, and secondary operative procedure was not needed in
      any patient in the follow-up. CONCLUSION: MTALT perforator flap with multiple
      perforators is safe and reliable for patients with complex defects on the hand,
      elbow, heel, or knee.

PMID- 29369172
TI  - Long noncoding RNA hypoxia-inducible factor 1 alpha-antisense RNA 1 promotes
      tumor necrosis factor-alpha-induced apoptosis through caspase 3 in Kupffer cells.
AB  - Kupffer cells (KCs) play a crucial role in the pathogenesis of acute-on-chronic
      liver failure (ACLF) which is characterized by acute and severe disease in
      patients with preexisting liver disease and shows high mortality. Long noncoding
      RNAs (lncRNAs) are recently found to be involved in gene regulation. However, the
      mechanisms of how KCs are regulated by inflammatory factors, tumor necrosis
      factor-alpha (TNF-alpha), and whether lncRNAs are involved in the process remain
      largely unknown. Hence, we investigated the role of lncRNAs in the cytotoxicity
      of TNF-alpha on KCs.lncRNA array (The lncRNAs in the array are apoptosis-related
      lncRNAs reported in some research papers.) was used to identify lncRNAs related
      with liver fibrosis. Annexin V/protease inhibitor (PI) staining was used for
      detection of cell apoptosis. Real time-polymerase chain reaction was utilized for
      analysis of mRNA levels of lncRNA hypoxia-inducible factor 1 alpha-antisense RNA
      1 (HIF1A-AS1) and apoptosis-related genes. Western blot was implied to the
      determination of lymphoid enhancer factor-1 (LEF-1).In this study, we found that
      HIF1A-AS1 could be upregulated by TNF-alpha by lncRNA array analysis and
      knockdown of HIF1A-AS1 significantly rescued cell apoptosis induced by TNF-alpha.
      Moreover, inhibition of HIF1A-AS1 markedly reduced mRNA level of caspase 3 which
      can be significantly enhanced by TNF-alpha. Furthermore, HIF1A-AS1 showed binding
      sites for LEF-1 and siRNA-mediated downregulation of LEF-1 decreased HIF1A-AS1
      level in KCs treated with TNF-alpha.This study elucidates a new role of HIF1A-AS1
      in TNF-alpha-induced cell apoptosis and provides potential therapeutic targets
      for ACLF.

PMID- 29369173
TI  - Restoration of the corticoreticular pathway following shunt operation for
      hydrocephalus in a stroke patient.
AB  - RATIONALE: We report on a stroke patient who showed restoration of discontinued
      corticoreticular pathways (CRPs) on serial diffusion tensor tractography (DTT)
      concurrent with recovery of gait disturbance following shunt operation for
      hydrocephalus. PATIENT CONCERNS: A 67-year-old female patient underwent
      stereotactic drainage for management of intraventricular hemorrhage due to a
      rupture of the left posterior communicating artery. DIAGNOSES: After 4 weeks from
      onset, the patient exhibited quadriparesis with more severe weakness in the
      proximal muscles and could not even stand or walk. She underwent comprehensive
      rehabilitation for 3 weeks. Her quadriparesis, as a result of hydrocephalus, did
      not improve significantly. INTERVENTIONS: On the pre-op DTT, discontinuations
      (the right CRP: at subcortical white matter level, and the left CRP: at the
      midbrain level) of the CRP fibers from the premotor cortex were observed in both
      hemispheres. OUTCOMES: She underwent a ventriculo-peritoneal shunt operation and
      her quadriparesis improved, especially the proximal muscles. Consequently, she
      could walk with mild assistance on an even floor at 5 days and walk on stairs at
      4 weeks after the shunt operation. On the post-op DTT, the discontinued CRP
      fibers were elongated to the premotor cortex in both hemispheres. LESSONS:
      Restoration of discontinued CRPs concurrent with recovery of gait disturbance
      following shunt operation for hydrocephalus was demonstrated in a stroke patient.

PMID- 29369174
TI  - A case report and literature review on fabella syndrome after high tibial
      osteotomy.
AB  - RATIONALE: The fabella is a normal structure, but is occasionally reported to
      cause posterior knee pain. The aim of this study was to present fabella syndrome
      after high tibial osteotomy. PATIENT CONCERNS: A 55-year-old female patient was
      admitted to the hospital due to about 1 year and 8 months of left knee pain.
      Sclerosis was observed in the anterior margin of the fabella in the preoperative
      magnetic resonance (MR) T2 image, and reactive bone marrow was found and was
      considered to be due to degeneration of the distal femur. Degenerative change
      (Kellgren and Lawrence-KL grade 2) of the left knee was observed, along with
      cartilage delamination corresponding to International Cartilage Repair Society
      (ICRS) grade 4 in the patellofemoral joint. DIAGNOSES: We present the first
      reported case of fabella syndrome in Korea, after high tibial osteotomy due to
      degenerative arthritis and varus deformity, rather than artificial joint surgery.
      INTERVENTIONS: We excised the fabella from the patient's knee. OUTCOMES: There
      was no evidence of recurrence during 5 months of postoperative follow-up.
      Posterolateral Corner including the fabella might have sustained increased
      tensile force causing symptoms due to compression of the fabella by the posterior
      joint of the posterior femoral condyle. LESSONS: We present the first reported
      case of fabella syndrome in Korea, after high tibial osteotomy due to
      degenerative arthritis and varus deformity, rather than artificial joint surgery.
      Collision syndrome caused by a fabella has previously been attributed to
      inconsistency of the joint surface due to excessive exercise and degenerative
      changes due to knee instability. We report this case since it appeared to involve
      collision syndrome due to mechanical change of an angular deformity.

PMID- 29369175
TI  - The relationship between cognitive function and arterial partial pressure O2 in
      patients with COPD: A meta-analysis.
AB  - BACKGROUND: The high incidence of cognition disorders in chronic obstructive
      pulmonary disease (COPD) patients represents a main focus in public health field
      recently. Thus, we tried to explore relationship between cognitive function and
      arterial partial pressure O2 (PaO2) in patients with COPD as assessed by Mini
      mental State Examination (MMSE) and/or Montreal Cognitive Assessment (MoCA).
      MATERIALS AND METHODS: Medical and scientific literature databases, such as Web
      of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure,
      and Wanfang Database, were searched independently by 2 reviewers until February
      2016. Correlation coefficient (r or rs) values were obtained from each study, and
      95% confidence intervals (CIs) were calculated using STATA12.0 software. RESULTS:
      A total of 2049 studies were produced, and 9 of which were analyzed (714
      participants) in the meta-analysis. The pooled r observed medium relationship for
      all selected studies (r = 0.405, 95% CI 0.31-0.55), and notable heterogeneity was
      also tested between studies (chi = 17.72, P = .023; I = 54.9%). After the
      sensitivity and subgroup analysis, the heterogeneity significantly decreased.
      Subgroup analysis showed that MMSE score was stronger correlation between PaO2
      and cognitive function than MoCA score in the COPD patients. Begg test did not
      indicate potential risk of publication bias. CONCLUSIONS: There was a negative
      correlation between cognitive function and anoxia in patients with COPD, so it
      may be extremely essential to predict and improve the status of hypoxia in COPD
      patients.

PMID- 29369176
TI  - Effect of platinum-based chemotherapy on EGFR gene mutation status in lung
      adenocarcinoma.
AB  - The aim of this study was to detect the epidermal growth factor receptor (EGFR)
      gene type at pre- and postchemotherapy to evaluate the impact of platinum-based
      chemotherapy on EGFR gene mutations and provide a theoretical foundation for
      clinical treatment.Around 40 serum DNA samples were collected from advanced
      nonsmall cell lung cancer patients who received platinum-based chemotherapy as
      first-line treatment in our hospital from August 1, 2014 to June 1, 2015. The
      EGFR gene exons 19 and 21 were amplified by polymerase chain reaction (PCR) and
      detected by direct sequencing. The outcomes were analyzed with SPSS 17.0.Of 40
      patients, 38 were included in the analysis. An EGFR gene mutation was detected in
      17 cases (44.7%) at prechemotherapy compared with 19 cases (50.0%) at
      postchemotherapy. The EGFR gene mutation differences were not statistically
      significantly (P = .165) during pre- and postchemotherapy. The EGFR gene type was
      consistent in 26 cases (68.4%). Among the 12 discordant cases, 5 cases changed
      from mutant type to wild type, while 7 cases changed from wild type to mutant
      type. EGFR mutation positive patients had a disease control rate (DCR) of 88.2%
      (15/17), whereas it was only 57.1% in EGFR mutation negative patients, which was
      statistically significant (P = 0.01) indicating a better curative effect in EGFR
      mutation positive patients.Platinum-based chemotherapy may change the serum EGFR
      gene type in advanced lung adenocarcinoma.

PMID- 29369177
TI  - Functional performance comparison between real and virtual tasks in older adults:
      A cross-sectional study.
AB  - INTRODUCTION: Ageing is usually accompanied by deterioration of physical
      abilities, such as muscular strength, sensory sensitivity, and functional
      capacity, making chronic diseases, and the well-being of older adults new
      challenges to global public health. OBJECTIVE: The purpose of this study was to
      evaluate whether a task practiced in a virtual environment could promote better
      performance and enable transfer to the same task in a real environment. METHOD:
      The study evaluated 65 older adults of both genders, aged 60 to 82 years (M =
      69.6, SD = 6.3). A timing coincident task was applied to measure the perceptual
      motor ability to perform a motor response. The participants were divided into 2
      groups: started in a real interface and started in a virtual interface. RESULTS:
      All subjects improved their performance during the practice, but improvement was
      not observed for the real interface, as the participants were near maximum
      performance from the beginning of the task. However, there was no transfer of
      performance from the virtual to real environment or vice versa. CONCLUSIONS: The
      virtual environment was shown to provide improvement of performance with a short
      term motor learning protocol in a timing coincident task. This result suggests
      that the practice of tasks in a virtual environment seems to be a promising tool
      for the assessment and training of healthy older adults, even though there was no
      transfer of performance to a real environment. TRIAL REGISTRATION:
      ISRCTN02960165. Registered 8 November 2016.

PMID- 29369178
TI  - Home-based cardiac rehabilitation improves quality of life, aerobic capacity, and
      readmission rates in patients with chronic heart failure.
AB  - BACKGROUND: Exercise tolerance and cardiac output have a major impact on the
      quality of life (QOL) of patients experiencing heart failure (HF). Home-based
      cardiac rehabilitation can significantly improve not only exercise tolerance but
      also peak oxygen uptake ((Equation is included in full-text article.)peak), and
      the QOL in patients with HF. The aim of this prospective study was to evaluate
      the beneficial effects of home-based cardiac rehabilitation on the quality of
      medical care in patients with chronic HF. METHODS: This study was a randomized
      prospective trial. HF patients with a left ventricular ejection fraction (LVEF)
      of less than 50% were included in this study. We randomly assigned patients to
      the control group (n = 18) and the interventional group (n = 19). Within the
      interventional group, we arranged individualized rehabilitation programs,
      including home-based cardiac rehabilitation, diet education, and management of
      daily activity over a 3-month period. Information such as general data,
      laboratory data, Cardiopulmonary Exercise Test (CPET) results, Six-minute Walk
      Test (6MWT) results, and the scores for the Minnesota Living with Heart Failure
      Questionnaire (MLHFQ) before and after the intervention, was collected from all
      patients in this study. RESULTS: Patients enrolled in the home-based cardiac
      rehabilitation programs displayed statistically significant improvement in
      (Equation is included in full-text article.)peak (18.2 +/- 4.1 vs 20.9 +/- 6.6
      mL/kg/min, P = .02), maximal 6-Minute Walking Distance (6MWD) (421 +/- 90 vs 462
      +/- 74 m, P = .03), anaerobic threshold (12.4 +/- 2.5 vs 13.4 +/- 2.6 mL/kg/min,
      P = .005), and QOL. In summary, patients receiving home-based cardiac
      rehabilitation experienced a 14.2% increase in (Equation is included in full-text
      article.)peak, a 37% increase in QOL score, and an improvement of 41 m on the
      6MWD test. The 90-day readmission rate for patients reduced to 5% from 14% after
      receiving cardiac rehabilitation. CONCLUSION: Home-based cardiac rehabilitation
      offered the most improved results in functional capacity, QOL, and a reduced the
      rate of readmission within 90 days.

PMID- 29369179
TI  - Targeted next-generation sequencing of malignant peripheral nerve sheath tumor of
      the pterygopalatine fossa with intracranial metastatic recurrence.
AB  - Malignant peripheral nerve sheath tumor (MPNST) is an uncommon neoplasm that
      rarely involves the head and neck region. Intracranial MPNSTs unrelated to
      cranial nerves are highly malignant tumors with poor overall survival, probably
      because of infiltrating growth into surrounding brain tissue. The pathogenesis of
      MPNST remains unclear. There are no conclusive explanations for the mechanisms
      underlying the initiation, progression, and metastasis of MPNST. In this paper,
      we describe a case of MPNST in the pterygopalatine fossa with intracranial
      metastatic recurrence and review related literatures. Meanwhile, targeted next
      generation sequencing (NGS) revealed the presence of both a beta-catenin (CTNNB1)
      missense mutation p.Ser33Phe and a mediator complex subunit 12 (MED12) frameshift
      mutation p.Tyr1278fs in the recurrent intracranial tumor. Therapies that target
      CTNNB1 mutation, MED12 mutation, CTNNB1 activation, or Wnt pathway activation are
      worth future studying.

PMID- 29369180
TI  - Primary cutaneous anaplastic large-cell lymphoma: A case report.
AB  - RATIONALE: Primary cutaneous anaplastic large-cell lymphoma (C-ALCL) is a rare
      cancer belonging to the group of primary T-cell lymphoproliferative diseases. C
      ALCL is characterized by the presence of single or multiple ulcerated lesions on
      the skin's surface. PATIENT CONCERNS: This is the case of a 73-year-old man who
      reported to the Clinic of Cranio-Maxillofacial and Oral Surgery and Implantology,
      Medical University of Warsaw, owing to a skin tumor in the right
      parotideomasseteric region, initially diagnosed as discoid lupus erythematosus.
      During treatment for discoid lupus erythematosus, biopsy was repeated because of
      significant disease progression and dynamic tumor growth. Histopathological
      examination revealed the presence of pilomatrix carcinoma (trichilemmal
      carcinoma). Because of the discrepancy between clinical and histopathological
      findings, the tumor specimen was submitted to another facility, wherein lymphoma
      infiltration by anaplastic large cells was found in the dermis and subcutaneous
      tissue. DIAGNOSIS: C-ALCL. INTERVENTIONS: The patient was transferred to the
      Lymphoid Tumours Clinic of the Maria Sklodowska Curie Memorial Cancer Centre and
      Institute of Oncology in Warsaw, where chemotherapy was initiated. OUTCOMES:
      After 4 cycles of chemotherapy, a complete remission of skin lesions was
      achieved. During the 5-year follow-up, no recurrence occurred. LESSONS: C-ALCL is
      a rare type of cancer. Misdiagnosis can lead to inappropriate therapy and result
      in disease progression or unnecessary harm to the patient.

PMID- 29369182
TI  - Association between social capital and quality of life among urban residents in
      less developed cities of western China: A cross-sectional study.
AB  - China has experienced rapid urbanization over the past several decades. Social
      capital is considered a vital human resource, and quality of life (QoL) is an
      important measure of human health embedded in a physical, mental, and social
      context. No studies have reported on the association between social capital and
      QoL in Chinese urban residents. We performed a cross-sectional study to
      investigate social capital in urban community residents of West China, and its
      relationship with QoL.Our study was carried out between June and July of 2015. A
      total of 1136 households were surveyed. The Chinese-translated version of the
      Short-Form Health Survey (SF-12) and social capital questionnaire were used to
      evaluate people's QoL and social capital. Associations between QoL and social
      capital were evaluated by 3 logistic regression analyses.A total of 1136 adult
      participants aged 18 years and older completed the questionnaire. Young residents
      were more likely to have lower second (SC2), third (SC3), and fourth (SC4)
      dimensions of social capital. Migrants and residents with higher education levels
      and high incomes showed lower SC1 and SC2 relative to other participants, and
      employed residents had relatively low SC1. Unmarried residents had lower SC2 and
      SC3. Without adjustment for potential confounding factors, participants with
      higher SC2 had higher average scores for mental components (MCS) of QoL [odds
      ratio (OR) = 1.48, 95% confidence interval (95% CI): 1.09-2.02], and the same was
      seen for SC3 (OR = 1.70, 95% CI: 1.24-2.34). After adjusting for socioeconomic
      status (SES) and risk factors, SC2 and SC3 were still significantly associated
      with MCS. Social capital was not significantly associated with physical
      components of QoL in any of the 3 logistic regression models.In conclusion,
      social capital is related to MCS of QoL, and increasing it may be an effective
      way to promote health.

PMID- 29369181
TI  - Revealing the action mechanisms of dexamethasone on the birth weight of infant
      using RNA-sequencing data of trophoblast cells.
AB  - Dexamethasone (DEX) could induce low birth weight of infant, and low birth weight
      has close associations with glucocorticoid levels, insulin resistance,
      hypertension, and metabolic syndrome in adulthood. This study was designed to
      reveal the action mechanisms of DEX on the birth weight of infant.Using
      quantitative real-time polymerase chain reaction (qRT-PCR), trophoblast cells of
      human placenta were identified and the optimum treatment time of DEX were
      determined. Trophoblast cells were treated by DEX (DEX group) or ethanol (control
      group) (each group had 3 samples), and then were performed with RNA-sequencing.
      Afterward, the differentially expressed genes (DEGs) were identified by R
      package, and their potential functions were successively enriched using DAVID
      database and Enrichr method. Followed by protein-protein interaction (PPI)
      network was constructed using Cytoscape software. Using Enrichr method and
      TargetScan software, the transcription factors (TFs) and micorRNAs (miRNAs)
      targeted the DEGs separately were predicted. Based on MsigDB database, gene set
      enrichment analysis (GSEA) was performed.There were 391 DEGs screened from the
      DEX group. Upregulated SRR and potassium voltage-gated channel subfamily J member
      4 (KCNJ4) and downregulated GALNT1 separately were enriched in PDZ (an acronym of
      PSD-95, Dlg, and ZO-1) domain binding and Mucin type O-glycan biosynthesis. In
      the PPI network, CDK2 and CDK4 had higher degrees. TFs ATF2 and E2F4 and miRNA
      miR-16 were predicted for the DEGs. Moreover, qRT-PCR analysis confirmed that SRR
      and KCNJ4 were significantly upregulated.These genes might affect the roles of
      DEX in the birth weight of infant, and might be promising therapeutic targets for
      reducing the side effects of DEX.

PMID- 29369183
TI  - Retrospective analysis of the utility of multiparametric MRI for differentiating
      between benign and malignant breast lesions in women in China.
AB  - We explored the utility of time-resolved angiography with interleaved stochastic
      trajectories dynamic contrast-enhanced magnetic resonance imaging (TWIST DCE
      MRI), readout segmentation of long variable echo-trains diffusion-weighted
      magnetic resonance imaging- diffusion-weighted magnetic resonance imaging
      (RESOLVE-DWI), and echo-planar imaging- diffusion-weighted magnetic resonance
      imaging (EPI-DWI) for distinguishing between malignant and benign breast
      lesions.This retrospective analysis included female patients with breast lesions
      seen at a single center in China between January 2016 and April 2016. Patients
      were allocated to a benign or malignant group based on pathologic diagnosis. All
      patients received routine MRI, RESOLVE-DWI, EPI-DWI, and TWIST DCE-T1WI.
      Variables measured included quantitative parameters (K, Kep, and Ve),
      semiquantitative parameters (rate of contrast enhancement for contrast agent
      inflow [W-in], rate of contrast decay for contrast agent outflow [W-out], and
      time-to-peak enhancement after contrast agent injection [TTP]) and apparent
      diffusion coefficient (ADC) values for RESOLVE-DWI (ADCr) and EPI-DWI (ADCe).
      Receiver-operating characteristic (ROC) curve analysis was used to evaluate the
      diagnostic utility of each parameter for differentiating malignant from benign
      breast lesions.A total of 87 patients were included (benign, n = 20; malignant, n
      = 67). Compared with the benign group, the malignant group had significantly
      higher K, Kep and W-in and significantly lower W-out, TTP, ADCe, and ADCr (all P
      < .05); Ve was not significantly different between groups. RESOLVE-DWI was
      superior to conventional EPI-DWI at illustrating lesion boundary and morphology,
      while ADCr was significantly lower than ADCe in all patients. Kep, W-out, ADCr,
      and ADCe showed the highest diagnostic efficiency (based on AUC value) for
      differentiating between benign and malignant lesions. Combining 3 parameters
      (Kep, W-out, and ADCr) had a higher diagnostic efficiency (AUC, 0.965) than any
      individual parameter and distinguished between benign and malignant lesions with
      high sensitivity (91.0%), specificity (95.0%), and accuracy (91.9%).An index
      combining Kep, W-out, and ADCr could potentially be used for the differential
      diagnosis of breast lesions.

PMID- 29369184
TI  - The effect of tourniquet usage on cement penetration in total knee arthroplasty:
      A prospective randomized study of 3 methods.
AB  - BACKGROUND: It is a randomized study to compare cement penetration on x-rays
      after total knee arthroplasty (TKA) among 3 different ways to use tourniquets;
      application during the surgery, application only with implantation prosthesis and
      with no tourniquet use. METHODS: A total 69 knees of 59 patients were included in
      the study in a quasirandom manner. Each patient had physical exams and standard
      radiographic evaluations at 6 weeks after the TKA procedure. Outcome evaluations
      included visual analog scale (VAS) scores, Knee Society Scores (KSS), blood
      transfusion, and drainage status after surgery for all groups. For radiographic
      review, the tibial plateau was divided into zones in the anterior-posterior and
      lateral views, according to the Knee Society Scoring System. RESULTS: The average
      age of the patients who were eligible for the study was 65.05 (range 46-81)
      years. All 59 patients included in the study were female patients. Group 1
      consisted of 24 patients who had TKA with use of a tourniquet during the entire
      operation. Group 2 consisted of 20 patients who had TKA with use of tourniquet
      only at the time of cementing and group 3 consisted of 25 patients with no use
      tourniquet. There is no significant difference in early cement penetration among
      the groups (group 1 2.50 mm, group 2 2.28 mm, group 3 2.27 mm; group 1 vs 2 P =
      .083, group 1 vs 3 P = .091, group 2 vs 3 P = .073). There is no significant
      difference for postoperative drainage among the 3 groups (group 1 245 mL, group 2
      258.76 mL, group 3 175.88 mL; group 1 vs 2 P = .081, group 1 vs 3 P = .072, group
      2 vs 3 P = .054). There was no need to transfuse more than 1 unit in any patient.
      The VAS score was significantly higher (group 1 3.58, group 2 1.55, group 3 1.52;
      group 1 vs 2 P = .022, group 1 vs 3 P = .018, group 2 vs 3 P = .062) and KSS was
      significantly lower in the tourniquet group (group 1 63, group 2 79, group 3 82;
      group 1 vs 2 P = .017, group 1 vs 3 P = .02, group 2 vs 3 P = .082). CONCLUSION:
      We do not suggest long-duration tourniquet use, which can lead higher pain scores
      and reduce functional recovery after total knee arthroplasty.

PMID- 29369185
TI  - Daily 10 mg rivaroxaban as a therapy for ventricular thrombus related to left
      ventricular non-compaction cardiomyopathy: A case report.
AB  - RATIONALE: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart
      disorder related to thrombosis. Anticoagulant therapy is suggested for the
      treatment of this disease. The success of the novel oral anticoagulant
      rivaroxaban as a treatment option for this disorder is unclear. PATIENT CONCERNS:
      A 43-year-old man who felt dizzy at rest was found to have an intraventricular
      thrombus. DIAGNOSES: The thrombus was confirmed by echocardiography. And LVNC was
      diagnosed by cardiac magnetic resonance (CMR) and echocardiography.
      INTERVENTIONS: He was prescribed a low dose (10 mg daily) of rivaroxaban as
      treatment. OUTCOMES: After 3 months, the thrombus diminished, and the
      manifestation disappeared. LESSONS: Low dose of rivaroxaban may serve as a viable
      option for anticoagulation therapy in LVNC patients, with large clinical trials
      needed to determine the best course of treatment.

PMID- 29369186
TI  - Cervical disc arthroplasty with Prestige-LP for the treatment of contiguous 2
      level cervical degenerative disc disease: 5-year follow-up results.
AB  - The objective of this study is to present the long-term results and to evaluate
      the safety and effectiveness of the Prestige-LP cervical disc replacement in
      treatment of patients with symptomatic 2-level cervical degenerative disc
      disease.Twenty-four patients with 48 Prestige-LP disc were analyzed before
      surgery and at 1 week, 3 months, 6 months, 12 months, 24 months, and 60 months
      after surgery. Clinical assessments included 36-Short Form (SF-36), Japanese
      Orthopedic Assessment (JOA), visual analog scale (VAS), and Neck Disability Index
      (NDI) scores. Radiographic assessments included cervical lordosis (CL), disc
      height (DH), range of motion (ROM) of the total cervical spine, functional spinal
      unit (FSU) as well as upper and lower operated segment. Complications at the 5
      year follow-up were collected as well.Mean follow-up period was 64.22 months.
      There was clinical improvement in terms of SF-36, JOA, NDI, and VAS from the
      preoperative to the final follow-up (P < .05). Overall, ROM of the total cervical
      spine, FSU, and upper and lower operated segment were maintained during the
      follow-up. Statistically significant (P < .05) improvements in the trend of CL
      and DH were noted at the follow-up. Eight patients were observed an appearance of
      heterotopic ossification at the 5-year follow-up, with 6 patients appeared at
      Class II and 2 patients at Class III. Adjacent segment degeneration assessed by
      radiographic evidence was found in 2 patients.Two-level cervical disc
      arthroplasty with Prestige-LP showed significant improvement in clinical outcomes
      at 5 years. It not only effectively preserves the motion of both total cervical
      spine and operated segments, but also restores normal CL and DH up to 5 years
      postoperation.

PMID- 29369187
TI  - Clinical application of MRI-respiratory gating technology in the evaluation of
      children with obstructive sleep apnea hypopnea syndrome.
AB  - The objective of the present study was to investigate the clinical application of
      magnetic resonance imaging (MRI)-respiratory gating technology for assessing
      illness severity in children with obstructive sleep apnea hypopnea syndrome
      (OSAHS).MRI-respiratory gating technology was used to scan the nasopharyngeal
      cavities of 51 children diagnosed with OSAHS during 6 respiratory phases.
      Correlations between the ratio of the area of the adenoid to the area of the
      nasopalatine pharyngeal cavity (Sa/Snp), with the main indexes of polysomnography
      (PSG), were analyzed. Receiver operator characteristic (ROC) curve and Kappa
      analysis were used to determine the diagnostic accuracy of Sa/Snp in pediatric
      OSAHS.The Sa/Snp was positively correlated with the apnea hypopnea index (AHI) (P
      < .001) and negatively correlated with the lowest oxygen saturation of blood
      during sleep (LaSO2) (P < .001). ROC analysis in the 6 respiratory phases showed
      that the area under the curve (AUC) of the Sa/Snp in the end-expiratory phase was
      the largest (0.992, P < .001), providing a threshold of 69.5% for the diagnosis
      of severe versus slight-moderate OSAHS in children. Consistency analysis with the
      AHI showed a diagnosis accordance rate of 96.0% in severe pediatric OSAHS and
      96.2% in slight-moderate pediatric OSAHS (Kappa = 0.922, P < .001).Stenosis of
      the nasopalatine pharyngeal cavity in children with adenoidal hypertrophy was
      greatest at the end-expiration phase during sleep. The end-expiratory Sa/Snp
      obtained by a combination of MRI and respiratory gating technology has potential
      as an important imaging index for diagnosing and evaluating severity in pediatric
      OSAHS.

PMID- 29369188
TI  - Human cytomegalovirus in high grade serous ovarian cancer possible implications
      for patients survival.
AB  - Patients diagnosed with high grade serous ovarian adenocarcinoma have a poor
      prognosis. Recently human cytomegalovirus (HCMV) has been detected in several
      tumors. Here, we evaluated HCMV in ovarian cancer tissue specimens obtained at
      pre- and postchemotherapy tumor resection.Available paraffin embedded ovarian
      cancer tissues from matched pre- and postchemotherapy tumor resection specimens
      (i.e., diagnostic excisional biopsy prechemotherapy; DEBPC) and neoadjuvant
      chemotherapy followed by interval debulking surgery (NACT + IDS) from 10 patients
      with stage IIIC-IV high grade serous ovarian carcinoma (HGS) diagnosed between
      years 2007 and 2008 at Karolinska University Hospital were examined for HCMV
      immediate-early protein (HCMV-IE), tegument protein pp65, and nucleic acid
      (beta2.7) by immunohistochemistry and in situ hybridization.HCMV-IE and pp65 were
      detected in 8/10 (80%), 4/9 (44%) and in 4/10 (40%), 5/8 in ovarian cancer tissue
      specimens from DEBPC and NACT + IDS, respectively. HCMV-beta2.7 was detected in
      all available tissue sections obtained from DEBPC and NACT + IDS. Patients with
      HCMV-IE or pp65 positive cells in their ovarian tumors at IDS after NACT had a
      median overall survival of 23.4 and 18.2 months, respectively, compared to 29.6
      and 54 months, respectively, in those who did not express HCMV proteins in their
      tumors.In conclusion, HCMV proteins and nucleic acids are frequently detected at
      different levels in HGS ovarian carcinoma. Despite the limitation of our study,
      shorter median overall survival of patients with HCMV-IE and pp65 in their tumor
      highlights the need to further investigate the role of HCMV in ovarian cancer
      patients.

PMID- 29369189
TI  - Drug-induced eosinophilic pneumonia: A review of 196 case reports.
AB  - BACKGROUND AND OBJECTIVE: Eosinophilic pneumonia (EP) is an important subset of
      patients who present with pulmonary infiltrates and eosinophilia (PIE). EP is
      classified by chronicity and etiology and drug-induced EP is the main cause of
      secondary EP. The primary goal of this review was to examine all the case reports
      published since the syndrome was defined in 1990. It remains unclear whether
      acute or chronic EP (AEP or CEP) represent different diseases, and the secondary
      goal of this review is to determine if there are factors that may help
      distinguish these 2 entities. METHODS: PubMed (MEDLINE and Medical Subject
      Headings) was searched for case reports of drug-induced EP or PIE syndrome
      published between 1990 and 2017. Case reports were only included if the
      diagnostic criteria for AEP or CEP were fulfilled. For each case, data were
      extracted pertaining to age, sex, type of medication associated with the disease,
      time from the onset of symptoms to diagnosis, eosinophil counts in the blood,
      eosinophil fractions in bronchoalveolar lavage (BAL) fluid, initial chest
      radiograph and computed tomography results, use of mechanical ventilation, and
      use of steroid treatment and recurrence. RESULTS: We found 196 case reports
      describing drug-induced EP. The leading cause was daptomycin. From our review, we
      found that AEP is more common in younger patients with no gender preference.
      Eosinophilia in the blood at the time of diagnosis characterized only the CEP
      patients (80% in CEP vs. 20% in AEP). Abnormal findings on radiographic imagine
      was similar in both syndromes. A significant portion of AEP patients (20%)
      presented with acute respiratory failure requiring mechanical ventilation. Most
      patients with EP were treated with steroids with a higher rate of relapse
      observed in patients with CEP. CONCLUSION: AEP is a much more fulminant and
      severe disease than the gradual onset and slowly progressive nature of CEP. The
      pathogenesis of AEP and CEP remains unclear. However, there is significant
      clinical overlap among AEP and CEP that are associated with drug toxicity,
      suggesting the possibility that AEP and CEP are distinct clinical presentations
      that share a common pathogenic pathway.

PMID- 29369190
TI  - Endometrial thickness as a predictor of the reproductive outcomes in fresh and
      frozen embryo transfer cycles: A retrospective cohort study of 1512 IVF cycles
      with morphologically good-quality blastocyst.
AB  - To evaluate the relationship between endometrial thickness during fresh in vitro
      fertilization (IVF) cycles and the clinical outcomes of subsequent frozen embryo
      transfer (FET) cycles.FET cycles using at least one morphological good-quality
      blastocyst conducted between 2012 and 2013 at a university-based reproductive
      center were reviewed retrospectively. Endometrial ultrasonographic
      characteristics were recorded both on the oocyte retrieval day and on the day of
      progesterone supplementation in FET cycles. Clinical pregnancy rate, spontaneous
      abortion rate, and live birth rate were analyzed.One thousand five hundred twelve
      FET cycles was included. The results showed that significant difference in
      endometrial thickness on day of oocyte retrieval (P = .03) was observed between
      the live birth group (n = 844) and no live birth group (n = 668), while no
      significant difference in FET endometrial thickness was found (P = .261) between
      the live birth group and no live birth group. For endometrial thickness on oocyte
      retrieval day, clinical pregnancy rate ranged from 50.0% among patients with an
      endometrial thickness of <=6 mm to 84.2% among patients with an endometrial
      thickness of >16 mm, with live birth rate from 33.3% to 63.2%. Multiple logistic
      regression analysis of factors related to live birth indicated endometrial
      thickness on oocyte retrieval day was associated with improved live birth rate
      (OR was 1.069, 95% CI: 1.011-1.130, P = .019), while FET endometrial thickness
      did not contribute significantly to pregnancy outcomes following FET cycles. The
      ROC curves revealed the cut-off points of endometrial thickness on oocyte
      retrieval day was 8.75 mm for live birth.Endometrial thickness during fresh IVF
      cycles was a better predictor of endometrial receptivity in subsequent FET cycles
      than FET cycle endometrial thickness. For those females with thin endometrium in
      fresh cycles, additional estradiol stimulation might be helpful for adequate
      endometrial development.

PMID- 29369191
TI  - Comparison of surgical and conservative treatment of Rockwood type-III
      acromioclavicular dislocation: A meta-analysis.
AB  - BACKGROUND: There is no consensus on the effects of surgical versus conservative
      treatment on Rockwood type-III dislocation of the acromioclavicular joint in
      general orthopedic practice. The objective of this meta-analysis was to compare
      the clinical outcomes of patients managed surgically and conservatively following
      type-III acromioclavicular (AC) dislocation. METHODS: The Cochrane Library,
      EMBASE, MEDLINE via Ovid SP, and PubMed databases were searched for randomized
      controlled trials and observational studies. Patient data were pooled using
      standard meta-analytic approaches. For continuous variables, the weighted mean
      difference was used. For dichotomous data, the odds ratio was calculated.
      RESULTS: The current analysis included 10 trials on this topic, and the results
      demonstrated that there were no significant differences between surgical and
      conservative treatment in terms of pain, weakness, tenderness, post-traumatic
      arthritis, restriction of strength, unsatisfactory function, and scores
      (Constant, UCLA, Imatani, SST, DASH, Larsen). Analyses of ossification of the
      coracoclavicular ligament (OR = 1.62, 95% CI = 1.01-2.61) and osteolysis of the
      lateral clavicle (OR = 2.87, 95% CI = 1.27-6.52) suggested better function with
      conservative treatment versus surgical treatment, but the latter was superior to
      conservative treatment with regard to loss of anatomic reduction. Only 1 study
      showed a higher acromioclavicular joint instability score for surgical management
      compared with conservative management (P < .00001). CONCLUSION: In the management
      of Rockwood type-III AC dislocation, conservative treatment is superior to
      surgical treatment. Nonoperative treatment results in a lower incidence of
      ossification of the coracoclavicular ligament and osteolysis of the lateral
      clavicle compared with operative treatment. However, there was no statistical
      difference between operative and nonoperative treatment in terms of clinical
      outcomes.

PMID- 29369192
TI  - Current trends in the management of Mirizzi Syndrome: A review of literature.
AB  - Mirizzi Syndrome is a rare and challenging clinical entity to manage. However,
      recent advances in technology have provided surgeons with new options for more
      effective diagnosis and treatment of this condition. This paper reviews these new
      diagnostic modalities and treatment approaches for the management of Mirizzi
      Syndrome.An online search language was performed using PubMed and Web of Science
      for literature published in English between 2012 and 2017 using the search terms
      "Mirizzi Syndrome" and "Mirizzi." In total, 16 case series and 11 case reports
      were identified and analyzed.The most frequently used diagnostic modalities were
      ultrasound, computed tomography (CT); magnetic resonance
      cholangiopancreaticography (MRCP); endoscopic retrograde
      cholangiopancreaticography (ERCP). A combination of >=2 diagnostic modalities was
      frequently used to detect Mirizzi Syndrome. Literature shows that the specific
      type of Mirizzi Syndrome determined the type of treatment chosen. Open surgery
      was the preferred option, although there are documented cases of the use of
      minimally-invasive techniques, even in advanced cases. Laparoscopic, endoscopic
      or robot-assisted surgery, used individually or in combination with lithotripsy,
      were all associated with a favorable outcome.As yet, there are no internationally
      accepted guidelines for the management of Mirizzi Syndrome. Laparotomy is the
      preferred surgical technique of choice, although an increasing number of surgeons
      are beginning to opt for minimally-invasive techniques. The number of papers in
      the existing literature describing diagnostic and treatment procedures is
      relatively small at present, thus making it difficult to reasonably propose an
      evidence-based standard of care for Mirizzi Syndrome.

PMID- 29369193
TI  - Fibrosing mediastinitis with pulmonary hypertension as a complication of
      pulmonary vein stenosis: A case report and review of the literature.
AB  - INTRODUCTION: Fibrosingmediastinitis (FM) is caused by a proliferation of fibrous
      tissue in the mediastinum encasing the mediastinal viscera that results in
      compression of mediastinal bronchovascular structures. Pulmonary hypertension
      (PH) is a severe complication of FM caused by extrinsic compression of pulmonary
      blood vessels. CASE PRESENTATION: Here, we present the case of a 47-year-old man
      who presented with a 10-year history of progressive hemoptysis and a 2-year
      history of shortness of breath, in whom a diagnosis of FM was made. Occlusion of
      the superior pulmonary veins was noted, with stenosis of the inferior pulmonary
      veins, leading to PH. Because the patient was a poor candidate for interventional
      catheterization, the preferred treatment for FM, his PH has been managed with
      diuretics, and he remains stable. CONCLUSIONS: FM is a serious, potentially life
      threatening condition that is best managed in specialized centers.

PMID- 29369194
TI  - Rapid improvement of angiostenosis due to isolated middle cerebral artery
      dissection: A case report.
AB  - RATIONALE: Intracranial arterial dissection is a rare cause of ischemic stroke,
      and isolated middle cerebral artery dissection (MCAD) is extremely rare, having
      been described only in sparse case reports. The etiology, clinicoradiological
      features, and treatment strategies are not yet well understood. PATIENT CONCERNS:
      A 49-year-old man presented with rapidly progressive aphasia and motor
      disturbance of the right limbs. DIAGNOSES: Neuroimaging evaluation confirmed a
      diagnosis of MCAD and cerebral infarction. INTERVENTIONS: The patient underwent
      oral anti-platelet therapy (100 mg aspirin daily). OUTCOMES: The patient
      recovered to normal status within 2 weeks following antiplatelet treatment.
      During a follow-up period of 2 years, he remained neurologically asymptomatic and
      led a virtually normal life. LESSONS: It is crucial for clinicians to be aware of
      this entity, as the diagnosis of MCAD is quite challenging. Antiplatelet therapy
      is effective for treating this condition, and the prognosis can be favorable.

PMID- 29369195
TI  - The effectiveness of Korean medicine treatment in male patients with infertility:
      a study protocol for a prospective observational pilot study.
AB  - : Male factor subfertility has increasingly been considered the cause of
      infertility in couples. Many men with male infertility have sperm problems such
      as oligozoospermia, asthenozoospermia, or teratozoospermia. Because abnormal
      semen parameters are idiopathic to some extent, no standard therapy has been
      established to date. Herbal medicine has been reported to have beneficial
      properties in the treatment of subfertility, especially in improving semen
      quality both in vivo and in human studies. Therefore, we intend to investigate
      the effectiveness and safety of treatment using Korean medicine (KM) for
      infertile male patients with poor semen quality.This will be a single-center,
      prospective, case-only observational pilot study. About 20 male patients with
      infertility who visit Conmaul Hospital of Korean Medicine will be recruited. We
      will follow the standard treatment protocol, which has shown good results in the
      treatment of male infertility. The protocol is composed mainly of a 10-week
      herbal decoction treatment; acupuncture and/or pharmacopuncture are added when
      needed. Semen samples, quality of life, and the scrotal temperatures of infertile
      men will be observed before and after the 10-week treatment with KM.The study has
      received ethical approval from the Public Institutional Review Board (approval
      number: P01-201708-21-008). The findings will be disseminated to appropriate
      audiences via peer-reviewed publication and conference presentations. TRIAL
      REGISTRATION: Korean Clinical Trial Registry (CRIS), Republic of Korea:
      KCT0002611.

PMID- 29369196
TI  - Tuina for children with cerebral palsy: A protocol for a systematic review.
AB  - BACKGROUND: Cerebral palsy (CP) describes a group of permanent disorders of
      movement and posture causing activity limitations, leading the most common
      movement disorder to children. On recovery of various aspects of CP, massotherapy
      has a good effect in a great many of Chinese clinical trials. Therefore, we plan
      to conduct a protocol of systematic review aimed at systematically reviewing all
      the clinical evidence on the effectiveness of massotherapy for treating CP in
      children. METHODS: The following electronic databases will be searched from
      inception to October 1, 2017: Cochrane Library, Web of Science, EBASE, Springer,
      World Health Organization International Clinical Trials Registry Platform, China
      National Knowledge Infrastructure, Wan-fang database, Chinese Biomedical
      Literature Database, Chinese Scientific Journal Database, and other sources. All
      published English and Chinese articles randomized controlled trials (RTCs) will
      be included. All types of CP of children in the trials will be included in this
      study and these individuals will be involved as coresearchers to evaluate the
      efficacy of massothreapy. RevMan V.5.3.5 software will be implemented for the
      assessment of bias risk, data synthesis, subgroup analysis, and meta-analyses if
      inclusion conditions are met. Continuous outcomes will be presented as mean
      difference (MD) or standard mean difference (SMD), while dichotomous data will be
      expressed as a relative risk. RESULTS: A high-quality synthesis of current
      evidence of massothreapy for children with CP will be provided from several
      aspects, including motor function improvement, intellectual development,
      improvement of self-care ability, and daily living. CONCLUSION: This protocol
      will present the evidence of whether Tuina threapy is an effective intervention
      for children with CP. ETHICS AND DISSEMINATION: There is no requirement of
      ethical approval and it will be in print or disseminated by electronic copies.
      PROSPERO REGISTRATION NUMBER: CRD42017080342.

PMID- 29369197
TI  - Different surgical approaches in laparoscopic sleeve gastrectomy and their
      influence on metabolic syndrome: A retrospective study.
AB  - Obesity is a growing health, social, and economic issue and became an epidemic,
      according to recent report of World Health Organization.The only method with
      scientifically proved efficiency of body mass loss is a surgical treatment.
      Laparoscopic sleeve gastrectomy (LSG) is recently a leading method in metabolic
      surgery. There are no standards of operative technique for LSG so far. The
      influence of technique modification on metabolic effect has not been described
      clearly.The aim of this study was to evaluate metabolic effects in patients with
      morbid obesity who underwent various surgical approaches of LSG.The study
      included 120 patients who were randomly divided into 3 groups: Group I, where
      bougie size was 32 French (Fr), Group II-36 Fr and Group III-40 Fr. Each group
      was divided into 2 subgroups, based on the distance of resection beginning from
      the pylorus-2 or 6 cm. Statistical analysis of: body mass index (BMI), the
      Percentage of Excess Weight Loss (%EWL), the Percentage of Excess BMI Loss
      (%EBMIL), levels of glucose and insulin on an empty stomach, glycated hemoglobin
      (HbA1c), insulin resistance (Homeostatic Model Assessment of Insulin Resistance
      Index-HOMA-IR), aspartate transaminase (AST), alanine transaminase (ALT), total
      cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL),
      triglycerides (TG), and C-reactive protein (CRP) were under
      investigation.Statistically significant decrease in body mass, BMI, %EWL, %EBL,
      glucose, and insulin concentrations has been observed in all studied groups. It
      was the highest when the smallest calibration tube has been used (32 Fr). Similar
      results were observed in HOMA-IR and HbA1c levels. Statistically significant
      decrease of total cholesterol, LDL, and TG concentrations have been observed.
      Significant increase of HDL in every group has been also noted. Postoperative CRP
      values were the lowest when the smallest bougie was used.LSG is effective method
      of obesity treatment. Metabolic effects of LSG are the most noticeable when a
      small bougie size is used.

PMID- 29369198
TI  - Prognostic significance of glypican-3 expression in hepatocellular carcinoma: A
      meta-analysis.
AB  - BACKGROUND: In recent years, an increasing number of studies has been published
      analyzing the possible prognostic utility of glypican-3 (GPC3) in hepatocellular
      carcinoma (HCC), but the results are still controversial. The aim of this meta
      analysis was to evaluate possible association between GPC3 expression and
      patients' survival. METHODS: Relevant publications which assessed GPC3 expression
      with survival outcome in HCC patients were searched from Pubmed, Embase, Web of
      Science, and the Cochrane library. Survival outcome (odds ratios or hazard
      ratios) was synthesized with a fixed or random effects meta-analysis. Publication
      bias and sensitivity analyses were also conducted. Statistical analysis was
      performed by STATA 12.0 and Review Manager software 5.3. RESULTS: Fifteen studies
      including 2336 HCC cases were analyzed systematically in our meta-analysis. The
      main results showed that GPC3 high expression was significantly associated with
      later tumor stage, higher tumor grade, presence of vascular invasion, shortened
      overall survival, and disease-free survival. Subgroup analyses for GPC3 on HCC
      overall survival according to the studies categorized by sample size, follow-up
      period, and cut-offs were also conducted. CONCLUSION: Our findings suggested that
      GPC3 may play a role in cancer invasion and progression and may be related to
      poor prognosis of HCC. Further mechanical research or multicenter cohort studies
      are needed to confirm these findings.

PMID- 29369199
TI  - Combined pretreatment serum CA19-9 and neutrophil-to-lymphocyte ratio as a
      potential prognostic factor in metastatic pancreatic cancer patients.
AB  - The aim of this study was to explore the role of combined pretreatment serum
      carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) as
      potential prognostic factors in metastatic pancreatic cancer patients.We
      investigated pretreatment serum CA19-9 and NLR in 59 metastatic pancreatic cancer
      patients, determined the patients' thresholds by receiver operating
      characteristic curve analysis, and assessed their prognostic values by Kaplan
      Meier curve and Cox regression models.Results of multivariate analysis showed
      high CA19-9, high NLR, and high score (the scoring system of CA19-9 and NLR) were
      significantly correlated with overall survival. Area under the curve of the
      scoring system was higher than that of CA19-9 or NLR.Combined pretreatment serum
      CA19-9 and NLR is a better prognostic biomarker of metastatic pancreatic cancer
      patients than CA19-9 or NLR alone.

PMID- 29369200
TI  - Effectiveness and confounding factors of penetrating astigmatic keratotomy in
      clinical practice: Case report.
AB  - RATIONALE: Penetrating astigmatic keratotomy (penetrating AK) is a well-known
      method to correct corneal astigmatism but rarely be performed nowadays. This
      article reevaluated the clinical effectiveness and confounding factors of
      penetrating AK. PATIENT CONCERNS: Penetrating AK has been introduced to serve as
      one alternative operation for astigmatism correction, and is thought to have the
      potential advantage of being more affordable and easy to perform. The purpose of
      our study is to evaluate the effectiveness and confounding factors of penetrating
      AK. DIAGNOSES: The chart of 95 patients with corneal astigmatism (range: 0.75
      3.25 diopters [D]) who received penetrating AK from January 2014 to December 2016
      was collected. The corneal astigmatism were measured by an autokeratometer
      (Topcon KR8100PA topographer-autorefractor), and repeated with manual keratometer
      in low reproducibility cases. INTERVENTIONS: All patients received penetrating AK
      by an experienced ophthalmologist (Dr. Gow-Lieng Tseng, MD, PHD) in the operation
      room. Among which, 66 patients received penetrating AK with phacoemulsification
      simultaneously (group A), whereas 29 patients received penetrating AK at least 3
      months after phacoemulsification (group B). After excluding the patients combined
      with other procedures or lost followed up, 79 patients are remaining for
      analysis. The outcome was evaluated by net correction, the difference between
      preoperative corneal astigmatism (PCA) and residual corneal astigmatism (RCA).
      Two sample t tests and Pearson test were used for effectiveness evaluation. For
      confounding factors, multivariate linear regression was used for statistical
      analysis. OUTCOMES: The mean preoperative and postoperative refractive cylinders
      were 1.97 +/- 0.77 and 1.08 +/- 0.64 D, respectively, in group A and 2.62 +/-
      1.05 and 1.51 +/- 0.89 D in group B. There were no statistically significant
      differences in net correction between these two groups (0.9 +/- 0.66 vs. 1.1 +/-
      0.69, P = .214). Higher PCA were associated with higher net correction in both
      group A (P = .002) and group B (P = .019). Compound myopic astigmatism caused
      less net correction than others only in group A (P = 0.031). LESSONS: Penetrating
      AK is an accessible, affordable, and effective way to correct corneal
      astigmatism. The results of this procedure are comparable to modern methods in
      patients with low to moderate corneal astigmatism.

PMID- 29369201
TI  - Avoiding excessive pregnancy weight gain to obtain better pregnancy outcomes in
      Taiwan.
AB  - Pregnancy weight gain may be associated with adverse pregnancy outcomes. The
      article aims to explore the relationship between weight change and pregnancy
      outcome in the Taiwanese pregnant women.The retrospective cohort study enrolled
      women with vertex singleton pregnancy at University-associated Hospital between
      2011 and 2014. Pregnancy weight change was separated into 3 groups, based on the
      Institute of Medicine (IOM) guidelines: below (n = 221); within (n = 544); and
      above (n = 382). Analysis of variance, chi tests, generalized linear models, and
      logistic regression models were used for statistical comparisons.Pregnant women
      with weight change above IOM guidelines had a significant increase in both
      maternal and perinatal complications compared with normal controls (odds ratio
      [OR] 1.65, 95% confidence interval [CI] 1.03-1.98; P = .043; OR 1.45, 95% CI 1.01
      1.87; P = .049, respectively). This finding was not found in pregnant women with
      weight gain below IOM guidelines. Moreover, age (OR 1.08, 95% CI 1.02-1.15; P =
      .0011), pre-pregnancy weight (OR 1.04, 95% CI 1.01-1.09; P = .0008), pre
      pregnancy body mass index (BMI; OR 1.15, 95% CI 1.06-1.30; P < .0001), weight at
      the time of delivery (OR 1.05, 95% CI 1.02-1.13; P < .0001) and BMI at the time
      of delivery (OR 1.15, 95% CI 1.06-1.39; P < .0001), all contributed to increased
      maternal complications but not perinatal complications, whereas parity (OR 0.23,
      95% CI 0.12-0.41; P < .0001) and gestational age (OR 0.50, 95% CI 0.35-0.62; P <
      .001) were associated with fewer maternal complications.Our study reconfirmed
      that for Taiwanese pregnant women, the approximate pregnancy weight gain
      recommended by IOM in 2009 was associated with the fewest maternal and perinatal
      complications. If approximate pregnancy weight gain cannot be attained, even less
      weight gain during pregnancy is still reasonable without significantly and
      adversely affecting maternal and perinatal outcomes in Taiwan.

PMID- 29369202
TI  - Palliative care with cervical intrathecal infusion and external pump for a late
      stage cancer patient with refractory pain: A case report.
AB  - RATIONALE: Intrathecal therapy, with a low complication rate, has become an
      alternative to standard pain management for treatment of neuropathic cancer pain.
      PATIENT CONCERNS: Here, we reported a late-stage cancer patient with intractable
      neuropathic pain in his right neck, shoulder, and upper limb. DIAGNOSES: The pain
      started 2 years ago when the patient was diagnosed as squamous cell carcinoma
      with metastasis to right supraclavicular lymph nodes. INTERVENTIONS: Cervical
      intrathecal infusion of morphine and bupivacaine with patient control analgesia
      by external pump was performed. The intrathecal catheter was located at the level
      of C6 vertebra. The initial concentration of bupivacaine and morphine were both 1
      mg/mL with infusion rate of 0.3 mL/h and bolus of 0.3 mL. Subsequently, the
      concentrations increased to 2 mg/mL (bupivacaine) and 1.33 mg/mL (morphine), with
      infusion rate to 0.6 mL/h and bolus to 0.5 ml. OUTCOMES: The pain intensity
      decreased from numerical rating scale 6 to 7 to 2 to 3 at rest, and from 10 to 5
      to 6 of breakthrough pain. LESSONS: In conclusion, cervical intrathecal infusion
      requires low concentration but high doses of bupivacaine and morphine, which is
      safe and effective in cancer patients with refractory pain and short life
      expectancy.

PMID- 29369203
TI  - Bilateral decompression and intervertebral fusion via unilateral fenestration for
      complex lumbar spinal stenosis with a mobile microendoscopic technique.
AB  - For complex lumbar spinal stenosis, using of endoscopy technique may provide
      clear vision with less invasive dissection of paravertebral muscle. The objective
      of this study was to evaluate the feasibility and clinical efficacy of bilateral
      decompression and intervertebral fusion via unilateral fenestration for complex
      lumbar spinal stenosis using mobile microendoscopic discectomy (MMED) technique.A
      total of 61 patients with complex lumbar spinal stenosis (lumbar canal stenosis
      combined with degenerative spondylolisthesis, instability, and scoliosis) were
      treated with this procedure. Patients with isolated lumbar spinal stenosis or
      spondylolisthesis greater than grade II were excluded. The index levels included
      L4/5 in 52 patients, L5/S1 in 6 patients, L3-L5 in 2 patients and L4-S1 in 1
      patient. The preoperative Oswestry Disability Index (ODI) score was 42.6 +/-
      10.2, lumbar visual analog scale (VAS) score was 6.1 +/- 4.2, and leg VAS score
      was 7.1 +/- 5.1. During the operation, ipsilateral enlarged fenestration was made
      using the MMED technique. The disc and cartilage endplate were thoroughly
      removed, and the contralateral ligamentum flavum and the inner layer of lamina
      were undercut to release the contralateral nerve root. The intervertebral space
      was released and prepared, followed by bone grafting and cage insertion.
      Percutaneous pedicle system was used for reduction and fixation. The operative
      time and blood loss were recorded, and patients were followed-up for at least 3
      years (36-48 months, average 41 months) to evaluate the clinical efficacy.The
      procedure was successful in all patients, with no nerve injury or conversion to
      open operation. The mean operative time was 120 minutes (range, 100-180 minutes),
      with a mean blood loss of 100 mL (range, 50-200 mL). Postoperative x-ray and CT
      showed sufficient decompression and improvement of spinal alignment. At 3 years
      after surgery, the ODI scores, lumbar and leg VAS scores decreased from
      preoperative 42.6 +/- 10.2, 6.1 +/- 4.2, and 7.1 +/- 5.1 to 8.6 +/- 7.0, 1.8 +/-
      1.3, and 0.9 +/- 0.6, respectively (P = .00 for each comparison). The clinical
      results were excellent in 36 cases, good in 23, and fair in 2, according to the
      MacNab scale.The procedure of bilateral decompression and intervertebral fusion
      via unilateral fenestration using the MMED technique can provide satisfactory
      clinical results for complex lumbar spinal stenosis.

PMID- 29369204
TI  - Chronic fatigue syndrome in Chinese middle-school students.
AB  - The objective of the present study was to determine the prevalence of chronic
      fatigue syndrome (CFS) and its associated factors in middle-school students in
      Suzhou, China. From September 2010 to January 2011, across-sectional study was
      conducted in junior- and senior middle-school students aged 10 to 18 years using
      a battery of confidential questionnaires. Our results indicate that 18,139
      completed the questionnaires effectively, of whom 163 (0.9%) met the definition
      of CFS, with senior high-school students and male students predominating. The
      prevalence of CFS in the middle-school students increased steadily with age. The
      main symptoms of CFS in these students included being afraid of going to school,
      despondency, and irritability in addition to those specified in the Centers for
      Disease Control and Prevention (CDC). Our study shows that CFS is prevalent among
      Chinese teenagers, and requiring proper intervention and treatment.

PMID- 29369205
TI  - Low recurrence rate of high-grade cervical intraepithelial neoplasia after
      successful excision and routine colposcopy during follow-up.
AB  - The aim of the present cohort study was to assess the long-term (follow-up period
      up to 22 years) recurrence rate of preinvasive disease and the newly detected
      invasive disease rate in a cohort of women treated with excisional methods for
      high-grade cervical intraepithelial neoplasia (CIN).Women treated with large loop
      excision of the transformation zone (LLETZ) and cold knife conization (CKC) for
      histologically proven high-grade CIN were followed up for up to 22 years.
      Surgical specimens underwent histological examination and the status of
      endocervical as well as ectocervical margins was recorded. Follow-up protocol
      included conventional Pap test, colposcopy and pelvic examination at 3, 6, and 12
      months after the initial treatment, and every 12 months thereafter, provided that
      the results were normal. In case of high-grade cytological findings and/or
      atypical colposcopic impression, multiple punch biopsies were taken in order to
      verify or exclude recurrent disease.In total, 804 women were followed for a mean
      time of 77.1 months (range: 6-266). LLETZ was used in 569 (70.7%) and CKC in 235
      cases (29.2%). No woman developed invasive cervical cancer. Recurrent high-grade
      disease, developed in 9 women (1.1%, 95% confidence interval 0.5-2.2). Median
      treatment-to-recurrence time was 46.5 months (range: 6-235.3). One woman treated
      for squamous CIN2 on clear margins developed adenocarcinoma in situ 59.2 months
      post-treatment.Women having undergone excisional treatment for high-grade CIN
      indicate a very low risk for recurrent disease and potentially negligible risk
      for invasive cancer, provided that a strict and vigorous follow-up is offered
      after treatment.

PMID- 29369206
TI  - Low-grade myofibroblastic sarcoma of gastric cardia on 18F-FDG positron emission
      tomography/computed tomography: An extremely rare case report.
AB  - RATIONALE: Low-grade myofibroblastic sarcoma (LGMS) is a rare mesenchyme-derived
      tumor, which usually occurs in head, neck (especially tongue and mouth), and
      limbs. In this report, we described a case of gastric LGMS by F-fluoro-2-deoxy-d
      glucose (FDG) positron emission tomography/computed tomography (PET/CT), which
      has not been reported previously. PATIENT CONCERNS: A 51-year-old female patient
      was admitted to our hospital with upper abdominal discomfort for 1 year and
      gradually increased eating difficulties over the last 3 months. From gastroscopy,
      an ulcer of 1.0 cm * 1.2 cm at the entrance of cardia and stiffness of peripheral
      mucosa were found, leading to suspicion of cardia cancer. F-FDG PET/CT was
      performed for further diagnosis and staging. DIAGNOSES: According to pathological
      findings in combination with immunohistochemical features, diagnosis of gastric
      LGMS was made. INTERVENTIONS: To relieve symptoms of upper gastrointestinal
      obstruction in the patient, proximal gastrectomy was carried out 1 week after the
      F-FDG PET/CT scan. OUTCOMES: The patient died due to advanced tumor. LESSONS: F
      FDG PET/CT scan showed local thickening of the gastric wall, invasion of adjacent
      soft tissue, diaphragmatic and peritoneal metastasis at early stage, absence of
      regional lymph node metastasis, and increased F-FDG metabolism in primary tumor
      and metastatic tumor.

PMID- 29369207
TI  - Prevalence of fear of falling and associated factors among Japanese community
      dwelling older adults.
AB  - To determine the prevalence of fear of falling and associated factors among
      Japanese community-dwelling older adults.Cross-sectional study between 2011 and
      2013.Community in which residents voluntarily attended a health examination.We
      recruited 844 older adults (male, n = 350; female, n = 494) aged 60 to 92 years
      from among those who presented at the health examination.We assessed fear of
      falling, falls in the previous year, pain, comorbidity, and cataracts. Five times
      chair stand time was applied as an indicator of physical performance.The
      prevalence of fear of falling was 26.9% and 43.3% among the men and women,
      respectively. Men and women who feared falling were older (P < .01), had longer 5
      times chair stand time (P < .01), and more falls in the previous year (P < .05),
      pain (P < .01), and comorbidity (P < .05). Multivariate logistic regression
      analysis identified advanced age (odds ratios [OR], 1.57; 95% confidence interval
      [CI], 1.03-2.39), falls in the previous year (OR, 2.44; 95%CI, 1.29-4.64), and
      pain (OR, 1.82; 95%CI, 1.03-3.22) in men, and advanced age (OR, 1.59; 95%CI, 1.13
      2.24), longer 5 times chair stand times (OR, 1.28; 95%CI, 1.04-1.59), falls in
      the previous year (OR, 2.59; 95%CI, 1.54-4.34), and pain (OR, 1.65; 95%CI, 1.06
      2.55) in women as being independently associated with fear of falling.The
      prevalence of fear of falling was similar to previous reports. Advanced age,
      falls in previous year, and pain were associated with fear of falling in men. A
      longer 5 times chair stand time was also associated with fear of falling among
      older adult women. Maintenance of physical function and pain management might be
      important for older adults with fear of falling.

PMID- 29369208
TI  - An alternative strategy treated giant congenital melanocytic nevi with epidermis
      and superficial dermis of the lesions.
AB  - Giant congenital melanocytic nevi (GCMN) are defined as rare pigmented lesions
      that are believed to form between weeks 9 and 20 of gestation. It is difficult to
      reconstruct large defects after the removal of the lesions and it has posed a
      great challenge to the plastic surgeon and dermatologist.Given all those
      difficulty reconstructing the defects, we try to explore an alternative way to
      resurfacing the defect after removal of GCMN.Patients with GCMN received single
      stage excision. Following the subcutaneous tissue and deep dermis were discarded,
      epidermis and superficial dermis were harvested as graft substitutes to
      reconstruct the defects in situ.All of the grafted tissue survived well and skin
      color in the surgical area gradually became lighter. During the periodicity of
      follow-up, neither hypertrophic scars nor recurrence were observed. Furthermore,
      histopathology examination demonstrated that there are no distinct melanocytes
      gathered in the postoperation lesions.For those GCMN which is difficult to
      reconstruct with traditional methods, resection of the lesion followed by
      reconstruction with epidermis skin and superficial dermis from the lesions in
      situ may be a feasible and alternative therapy method.

PMID- 29369211
TI  - Preoperative intravenous glucocorticoids can decrease acute pain and
      postoperative nausea and vomiting after total hip arthroplasty: A PRISMA
      compliant meta-analysis: Erratum.

PMID- 29369209
TI  - Bone marrow granulomas in a high tuberculosis prevalence setting: A
      clinicopathological study of 110 cases.
AB  - Granulomas were reported in 0.3% to 3% of bone marrow biopsies. The aim of the
      study was to evaluate the incidence and etiology of bone marrow granulomas (BMGs)
      in the West China Hospital, which located at a high tuberculosis (TB) prevalence
      area in China.A retrospective case review was performed on 11,339 bone marrow
      biopsies at the West China Hospital of Sichuan University between January 2011
      and December 2015. Cases with BMGs were retrieved and their clinical data and
      histopathological features were collected, examined, and analyzed.Out of 11,339,
      110 cases showed granulomatous lesions in the bone marrow biopsies (0.97%).
      Etiologies were indentified in 80 cases (72.8%), with infections being the most
      common (64.5%), following by malignancies (4.5%) and autoimmune diseases (3.6%).
      Among infectious cases, 87.32% (62/71) cases were diagnosed as TB, a positive
      acid-fast stain or/and polymerase chain reaction (PCR) result for mycobacterium
      TB DNA fragment amplification was obtained for 35 cases. In 30 cases (27.27%), a
      definite diagnosis could not be established.In a TB high prevalence region in
      China, with a combined histological, clinical, serological, and molecular
      approach, we were able to clarify the cause in 72.73% of the bone marrow
      granulomatous cases. TB is the most common underlying etiologies. Therefore, acid
      fast stain and quantitative PCR for mycobacterium TB DNA amplification are
      recommended as a routine for bone marrow biopsies in TB high prevalence regions.

PMID- 29369210
TI  - Prognostic role of pretreatment neutrophil to lymphocyte ratio in breast cancer
      patients: A meta-analysis: Erratum.

PMID- 29369212
TI  - Nonsurgical management of an extensive spontaneous spinal epidural hematoma
      causing quadriplegia and respiratory distress in a choledocholithiasis patient: A
      case report: Erratum.

PMID- 29369213
TI  - Efficacy of Lactobacillus reuteri DSM 17938 for infantile colic: Systematic
      review with network meta-analysis: Erratum.

PMID- 29369214
TI  - Ginseng for improving semen quality parameters: A protocol of systematic review.
AB  - BACKGROUND: The aim of this systematic review is to determine whether ginseng is
      effective in improving sperm quality. METHODS AND ANALYSIS: Twelve databases will
      be searched from their inception to the present date: PubMed, EMBASE, AMED, the
      Cochrane Library, 5 Korean medical databases (KoreaMed, DBpia, OASIS, the
      Research Information Service System [RISS], and the Korean Studies Information
      Service System [KISS]), and 3 Chinese medical databases (China National Knowledge
      Infrastructure [CNKI], the Wanfang Database, and the Chinese Scientific Journals
      Database [VIP]). We will include all prospective clinical trials including
      randomized controlled trials (RCTs), controlled trials, and uncontrolled
      observational studies. We will exclude case study and case series, and
      retrospective studies in which healthy men or men with subfertility are treated
      with any type of ginseng. We will exclude studies comparing the 2 different forms
      of ginseng. The selection of the studies, data abstraction, and validations will
      be performed independently by 2 researchers. The risk of bias of the RCTs will be
      evaluated using the Cochrane's risk of bias assessment tool. ETHICS AND
      DISSEMINATION: The findings will be disseminated to appropriate audiences via
      peer-reviewed publications and conference presentations. Our review will provide
      readers the opportunity to access studies originally published in East Asian
      languages that they would otherwise be unable to read. TRIAL REGISTRATION NUMBER:
      PROSPERO 2017 CRD42017078797.

PMID- 29369215
TI  - Association between daily life experience and psychological well-being in people
      living with nonpsychotic mental disorders: Protocol for a systematic review and
      meta-analysis.
AB  - BACKGROUND: Evidence has shown that people living with nonpsychotic mental
      disorders experience difficulties in maintaining their daily living, consequently
      impacting on psychological well-being. However, the role of daily life experience
      remains unclear. This systematic review and meta-analysis aims to determine the
      association between daily life experience and psychological well-being in people
      living with nonpsychotic mental disorders, and evaluate daily life experience as
      a moderator of psychological well-being in this population. METHODS: Literature
      search will be performed using a combination of title/abstract words and subject
      headings on 7 electronic databases according to predefined inclusion and
      exclusion criteria. Data will be extracted by 4 independent reviewers (JH, SPCN,
      WKKW, and WKH). Disagreement will be resolved by discussion with senior
      reviewers. Observational studies involving subjects with unipolar depression,
      bipolar disorder, anxiety disorder, acute stress disorder, as post-traumatic
      stress disorder as distinct groups with quantitative measurement of daily life
      experience and psychological well-being will be included. RESULTS: Effect sizes
      will be pooled by random effects model. The quality of the studies will be
      assessed using Newcastle-Ottawa scale. Heterogeneity between studies will be
      quantified using I index. This review is registered in PROSPERO. CONCLUSIONS:
      While symptoms and existing treatments of nonpsychotic mental disorders could be
      long term and dependent upon medical regimens, sustaining daily life experience
      will be a potentially important and concrete pathway that empowers patients to
      recover from the disorders, maintain or enhance psychological well-being, and be
      reintegrated into society. Findings of this review will inform prospective
      interventional trials of enhancing daily life experience in prevention of
      recurrence and enhancing psychological well-being in people living with
      nonpsychotic mental disorders.

PMID- 29369216
TI  - Helicobacter pylori eradication may influence timing of endoscopic surveillance
      for gastric cancer in patients with gastric precancerous lesions: A retrospective
      study.
AB  - Chronic atrophic gastritis and intestinal metaplasia related to Helicobacter
      pylori infection, are major risk factors for gastric adenocarcinoma. Eradication
      of H pylori and endoscopy surveillance of precancerous lesions may reduce the
      risk and/or lead to early detection of gastric cancer improving survival. In this
      study, the progression of precancerous lesions after H pylori treatment was
      evaluated.Patients with incomplete or complete intestinal metaplasia and/or
      gastric atrophy at the index endoscopy, were examined for the
      extension/histological worsening of precancerous lesions at the endoscopy
      surveillance for gastric cancer. Progression of lesions was evaluated according
      to H pylori status, age, and sex. Cox proportional hazard regression model and
      Kaplan-Meier curves were used to evaluate the strength of predictors for lesions
      progression.Among 105 patients (61 women) H pylori negative patients showed a
      milder worsening of gastric lesions between index and surveillance endoscopy
      compared with patients positive for the infection (log-rank test: P < .0001, P =
      .012, and P = .032 for antrum, angulus, and corpus, respectively). The Cox
      regression model showed persistence of H pylori infection (hazard ratio = 4.436;
      P < .0001) as the only relevant factor for lesion progression, whereas age >65
      years and sex were not significant predictors.According to literature our results
      demonstrate that H pylori eradication is the major factor able to delay gastric
      precancerous lesions progression. Time interval for endoscopic surveillance in
      patients negative for H pylori infection and with gastric precancerous lesions
      may be extended.

PMID- 29369217
TI  - Herbal medicine (Danggui Liuhuang decoction) for managing menopausal symptoms: A
      protocol of systematic review of randomized clinical trials.
AB  - BACKGROUND: Danggui Liuhuang (DLH) decoction is a traditional herbal medicine
      that is widely used in East Asia to treat menopausal symptoms. Most of the
      available clinical trials that investigated DLH decoction have been included in
      this review. The objectives of this protocol are to provide the information of
      how to evaluate the effectiveness and safety of DLH decoction for the treatment
      of menopausal symptoms. METHODS AND ANALYSIS: Fourteen databases will be searched
      from inception until February 2018. We will include randomized controlled trials
      (RCTs) testing any type of DLH decoction. All RCTs investigating DLH decoction or
      modified DLH decoction will be included. The methodological quality of the RCTs
      will be evaluated using the Cochrane's risk of bias assessment tool. ETHICS AND
      DISSEMINATION: The full systematic review will be published in a peer-reviewed
      journal. The review will also be disseminated electronically and in print.
      Updates of the review will be conducted to inform and guide healthcare practice
      and policy. TRIAL REGISTRATION NUMBER: PROSPERO 2017 CRD42017079189.

PMID- 29369218
TI  - The association of hypernatremia and hypertonic saline irrigation in hepatic
      hydatid cysts: A case report and retrospective study: Erratum.

PMID- 29369220
TI  - Insulin autoimmune syndrome in a pregnant female: A rare case report: Erratum.

PMID- 29369219
TI  - A primary gastric synovial sarcoma: A case report and literature review: Erratum.

PMID- 29369221
TI  - The association of single nucleotide polymorphism rs189037C>T in ATM gene with
      coronary artery disease in Chinese Han populations: A case control study.
AB  - Accumulated evidence has indicated that ataxia telangiectasia mutated (ATM) is
      closely related to atherosclerosis and cardiovascular diseases. So we aimed to
      examine potential association between a gene variant [single nucleotide
      polymorphisms (SNPs), i.e., rs189037C>T] in the promoter of ATM gene and coronary
      artery disease (CAD) in Chinese Han populations.In this hospital-based case
      control study, a total of 1308 participants were divided into CAD group (652
      patients) and control group (656 subjects) after performing coronary angiography.
      The SNP rs189037 was genotyped by using polymerase chain reaction-restriction
      fragment length polymorphism.The distribution of rs189037 genotypes and alleles
      showed a significant difference between CAD and control subjects (genotypes: P =
      .032; alleles: P = .028). The percentage of the TT genotype is much higher in
      control group than that in CAD group (22.0% vs 16.3%, P = .009). After adjustment
      of the major confounding factors, such difference remained significant (OR =
      0.62, 95% CI = 0.43-0.89, P = .010). After analyzing data from different groups
      divided by genders and smoking status respectively, we found that the protective
      effect of TT genotype on CAD was significant in males (P = .007) and smokers (P =
      .031). The difference remained statistically significant after multivariate
      adjustment (adjusted in males: OR = 0.60, 95% CI = 0.38-0.93, P = .022; adjusted
      in smokers: OR = 0.47, 95% CI = 0.27-0.81, P = .006).Our study suggests that ATM
      rs189037 polymorphism is associated with CAD in Chinese Han populations. The TT
      genotype of rs189037 seems to be associated with a lower risk of CAD and a
      protective genetic marker of CAD, especially in males and smokers.

PMID- 29369222
TI  - Prognostic impact of left ventricular mass change in patients with ST-elevation
      myocardial infarction.
AB  - Prognostic significance between progression of left ventricular hypertrophy (LVH)
      and clinical outcomes in patients with ST-elevation myocardial infarction (STEMI)
      is uncertain. The objective of this study was to investigate prognostic impact of
      progression of LV mass index (LVMI) in patients with STEMI.We analyzed the data
      and clinical outcomes of patients with STEMI who received successful coronary
      intervention. A total of 200 patients who had echocardiographic follow-up between
      12 and 36 months were finally enrolled. According to change in LVMI compared to
      baseline LVMI, patients were classified into progression group and nonprogression
      group. Progression of LVMI was defined when increment of LMVI was greater than
      10% compared to baseline LVMI. End points were major adverse cardiac events
      within 5 years, including death, recurrent MI, target vessel revascularization,
      and hospitalization due to heart failure.Progression of LVMI occurred in 55
      patients. In the progression group, rate of recurrent MI was higher (13 vs 2%, P
      = .026) and the event-free survival of recurrent MI was significantly worse (log
      rank P < .001) than that in the nonprogression group. Adjusted hazard ratio of
      progression of LVMI for recurrent MI was 10.253 (95% confidence intervals 2.019
      52.061, P = .005).Increased LVMI was an independent predictor for adverse events,
      especially for recurrent MI, in patients with STEMI.

PMID- 29369223
TI  - Intramedullary fixation versus plate fixation for displaced mid-shaft clavicle
      fractures: A systematic review of overlapping meta-analyses.
AB  - BACKGROUND: Displaced mid-shaft clavicle fractures (DMCFs) are common injuries.
      Both intramedullary fixation (IMF) and plate fixation (PF) have been described
      and routinely used. Multiple trials have been conducted to compare these
      treatments. Multiple meta-analyses have been published to compare IMF and PF
      treatment for DMCFs; however, the results remain controversial. The purposes of
      this study were to perform a systematic review of overlapping meta-analyses
      comparing IMF and PF treatment for DMCFs, to help decision makers critically
      evaluate the current meta-analyses, and to propose a guide through the best
      available evidence. METHOD: We searched the Cochrane library, PubMed, and EMBASE
      data bases. Two authors independently scanned titles and abstracts to exclude
      irrelevant articles and identify meta-analyses that met the eligibility criteria.
      The methodological quality of the meta-analysis was independently assessed by the
      2 authors using the Oxford Centre for Evidence-based Medicine Levels of Evidence
      and the Assessment of Multiple Systematic Reviews (AMSTAR) tool. Heterogeneity
      information of each variable was extracted from the included studies. An I of
      <60% is accepted in this systematic review. The Jadad algorithm was then applied
      to determine which of the meta-analyses provided the best evidence. RESULTS:
      Eight meta-analysis met the inclusion criteria in this study. AMSTAR scores
      varied from 7 to 9. Heterogeneity of each outcome was acceptable. Four authors
      independently selected the same meta-analysis as providing the highest quality of
      evidence using the Jadad decision algorithm. CONCLUSION: This systematic review
      of overlapping meta-analyses suggests that compared with PF, major reintervention
      and refracture after implant removal occurred more frequently after PF of DMCFs.
      No differences in terms of function and non-union between PF and IMF were
      observed. Future research should focus on fracture selection for IMF and further
      improvement of plates and IM devices.

PMID- 29369225
TI  - Serum 25-hydroxyvitamin D and risk of type 2 diabetes in older adults: A dose
      response meta-analysis of prospective cohort studies: Retraction.

PMID- 29369224
TI  - Sorafenib prescribed by gastroenterologists and hepatologists for hepatocellular
      carcinoma: A retrospective, multi-institutional cohort study.
AB  - Sorafenib is the only Food and Drug Administration (FDA)-approved first-line
      therapy shown to have survival benefit for patients with advanced hepatocellular
      carcinoma (HCC). Patients with advanced HCC are often but not exclusively
      transferred from non-oncologists to oncologists to initiate systemic therapy. The
      objective of this study was to assess whether sorafenib prescribing by non
      oncologists has any impact on utilization, adverse effects, cost or outcome.This
      was a retrospective cohort study utilizing data from patients prescribed
      sorafenib for HCC within Veterans Health Administration hospitals with 100% chart
      abstraction to confirm HCC diagnosis, identify prescribing provider specialty
      (oncology versus gastroenterology/hepatology), and obtain data required for
      cancer staging by the Barcelona Clinic Liver Cancer (BCLC) system. The primary
      outcome was overall survival from the time of sorafenib prescription.A total of
      4903 patients who prescribed sorafenib for HCC were identified, for whom 340
      patients (6.9%) were prescribed drug by a non-oncologist (Onc). BCLC Stage, age,
      Child-Turcotte-Pugh score, and comorbidity indices were similar between patients
      prescribed sorafenib by oncologists and non-oncologists. Oncologists more often
      discontinued sorafenib due to progression, whereas non-oncologists were more
      likely to continue sorafenib until death resulting in greater pill utilization
      and cost. Overall survival in both unadjusted and multivariable models showed no
      significant impact of prescriber type on survival (222 vs 217 days, P = .96),
      confirmed with propensity-matched subcohorts.Similar survival outcomes were
      observed for patients with HCC prescribed sorafenib by non-oncologists and
      oncologists, suggesting that non-oncologists with expertise in the management of
      HCC can safely and effectively administer sorafenib.

PMID- 29369226
TI  - The efficiency and safety of tranexamic acid for reducing blood loss in open
      myomectomy: A meta-analysis of randomized controlled trials: Retraction.

PMID- 29369227
TI  - Silicone Hydrogel and Rigid Gas-Permeable Scleral Lens Tear Exchange.
AB  - OBJECTIVES: To quantify tear elimination rate (ER) underneath silicone hydrogel
      (Si-Hy) and scleral gas permeable (GP) contact lenses (CLs). METHODS: Subjects
      successfully using either well-fitting soft Si-Hy CLs or scleral GP CLs were
      recruited. Most scleral GP CL wearers had irregular corneas (e.g., keratoconus).
      An objective fluorometer measured decay of fluorescein isothiocyanate dextran dye
      signal (70 kD MW) from which the tear ER in %/min was calculated. For GP scleral
      lenses, the ER was determined for both the initial settling period and the 30- to
      60-min period, and without lenses. All ERs were calculated from 5 to 30 min to
      avoid reflex tearing effects. RESULTS: Fourteen soft Si-Hy CL and 12 scleral GP
      CL wearers completed the study. The ER for the scleral GP CL wearers averaged
      0.57 (+/-0.6) %/min for the 0- to 30-min and 0.42 (+/-0.5) %/min for the 30- to
      60-min period (P=0.515). Non-CL wear tear ER in these same subjects averaged
      34.17 (+/-15.9) %/min and was significantly different versus both scleral GP wear
      periods (both P values <0.001). The ER for the soft Si-Hy CL wearers, 5 to 30
      min, averaged 6.09 (+/-2.8) %/min. CONCLUSIONS: Our data demonstrate
      significantly less ER in well-fit scleral GP CL wearers compared with soft Si-Hy
      CL wearers for both the settling and longer wear periods (both P values <0.001).
      Moreover, slightly greater tear exchange was observed during the scleral GP CL
      settling period than later, which may reflect a change over time in tear vault
      thickness.

PMID- 29369228
TI  - Consequences of Preservative Uptake and Release by Contact Lenses.
AB  - OBJECTIVES: To assess contact lens preservative uptake and release from
      multipurpose solutions (MPS) and subsequent acquisition of lens antibacterial
      activity. METHODS: Kinetics of uptake and release of poly (hexamethylene
      biguanide hydrochloride) (PHMB) or polyquaternium-1 (PQ-1) from various contact
      lenses were studied initially with the pure compounds and then after soaking in
      MPS containing these compounds. Lenses soaked in MPS were tested for
      antibacterial activity. RESULTS: Only lenses with a negatively charged component
      absorbed these preservatives. For lenses containing methacrylic acid (MA), uptake
      of PHMB from preservative-only solution was fast, yet little was released, in
      contrast to its rapid release from lenses containing other anionic groups. This
      trend persisted with PHMB-containing MPS. PQ-1 from preservative-only solution
      was only absorbed by lenses containing MA and was released from MA-containing
      hydrogels, but not significantly from an MA-containing silicone hydrogel. Lens
      uptake of PQ-1 was much lower from MPS and release was essentially undetectable
      from all lenses evaluated. Antibacterial lens activity was acquired by lenses
      containing MA after an overnight soak in MPS containing PQ-1, and for balafilcon
      A and omafilcon A after 5 exchanges in PHMB-containing MPS. Acquired activity was
      maintained during cycling between artificial tear protein solution and MPS.
      CONCLUSIONS: Lens preservative uptake and its subsequent release are dependent on
      lens chemistry, preservative nature, and other MPS components. A few
      lens/solution combinations acquired antibacterial activity after one or more
      overnight soaks in MPS, depending on the nature of the anionic lens component and
      the preservative. Uncharged lenses did not acquire antibacterial activity.

PMID- 29369229
TI  - Stenotrophomonas maltophilia-A Case Series of a Rare Keratitis Affecting Patients
      With Bandage Contact Lens.
AB  - OBJECTIVES: Stenotrophomonas maltophilia is an opportunistic pathogen known to
      form biofilms on contact lens and case surfaces that may result in permanent
      visual loss in cases of microbial keratitis. Because of its multiple drug
      resistance and extremely low incidence, there is little consensus on treatment.
      We investigated the predisposing factors, management, and visual outcomes in a
      small case series of patients to better inform the management of this rarely
      reported keratitis. METHODS: Retrospective analysis of medical records was
      performed at a single tertiary referral center between 2011 and 2017. The case
      notes of each microbiology confirmed S. maltophilia keratitis were examined.
      RESULTS: Six cases were identified (four men) with a median age of 62 years
      (range 1 month-90 years) and pre-existing ocular surface disease in all cases. At
      presentation, four patients were using bandage contact lenses and three were on
      topical antibiotic and steroid medications. Initial antibiotic treatment was
      intensive topical 0.3% ofloxacin and 5% cefuroxime, which was modified based on
      corneal scrape culture and sensitivity and clinical findings. One patient chose
      not to complete the treatment course. The 5 remaining patients had complete
      resolution of ulceration over a mean of 2.9 months (SD 0.8 months). CONCLUSIONS:
      Contact lens in the context of ocular surface problems, prolonged topical
      antibiotic and steroid treatments may predispose to S. maltophilia, a rare cause
      of keratitis. We report successful treatment with case-specific combinations of
      topical antibiotics such as fluoroquinolone, cotrimoxazole, and/or cephalosporin
      agents, although visual outcomes remain poor due to corneal scar.

PMID- 29369230
TI  - Longitudinal Changes in Disc and Retinal Lesions Among Highly Myopic Adolescents
      in Singapore Over a 10-Year Period.
AB  - OBJECTIVES: To examine the progression pattern of disc and retinal lesions in
      highly myopic Chinese adolescents over a 10-year period in Singapore. METHODS:
      This longitudinal study included Chinese participants who showed high myopia
      (spherical equivalent [SE] worse than or equal to -5 diopters [D]), no history of
      refractive surgery, and available fundus photographs at both 2006 (baseline) and
      2016 (10-year follow-up) visits. Forty-four adolescents (aged 12-16 years at
      baseline) who were re-examined later at follow-up were included. Cycloplegic
      refraction, biometry, and fundus photography were performed at both visits. A
      trained grader classified myopic macular degeneration (MMD) based on the Meta
      pathologic myopia classification and disc lesions from fundus photographs.
      Choroidal thickness (CT) measurements were performed at 10-year follow-up using
      swept-source optical coherence tomography. The ocular parameters and lesions were
      compared between baseline and follow-up. RESULTS: There was a significant
      worsening of high myopia at follow-up to -7.5+/-1.8 D (mean SE+/-SD) in 2016
      versus -6.2+/-1.3 D in 2006; (P<0.001). The 10-year changes included increased
      degree of tessellation (26 eyes, 29.5%), development of new tessellated fundus
      (19 eyes, 21.6%), disc tilt (7 eyes, 8.0%), and expansion of peripapillary
      atrophy size (33 eyes, 37.5%). Eyes with early-onset tessellation (present at
      baseline, 48 eyes) showed significantly thinner CT (P<0.05), compared with eyes
      with late-onset tessellation (incident at 10-year follow-up, 19 eyes). No cases
      of MMD were recorded at baseline or 10-year follow-up. CONCLUSIONS: Although
      there was no incident MMD, the retinal and disc lesions worsened over the follow
      up period. Early-onset fundus tessellation was associated with thinner CT.

PMID- 29369231
TI  - Does Occupation Influence Selection of Contact Lens Material?
AB  - OBJECTIVE: Long-term follow-up of contact lens (CL) wearers leads to better
      understanding of the factors leading to changes in CL trends. This study is an
      attempt to ascertain these factors in an emerging market like India. Factors like
      occupation were analyzed to determine if these contributed to changes in
      selection of CL materials in this article. METHODS: Occupations were categorized
      as per the norms of International Standard Classification of Occupations-2008
      (International Labor Organization, United Nations organization). RESULTS: A
      majority of lens wearers were professionals and hydrogel lens materials were the
      lenses of choice among most of the lens wearers. There was a significant
      variation in CL material with different occupations (chi=19.29, P=0.037).
      CONCLUSION: To conclude, employment and affordability influenced the selection of
      lens materials.

PMID- 29369233
TI  - Relationship Between Race, Insurance Coverage, and Visual Acuity at the Time of
      Cataract Surgery.
AB  - OBJECTIVE: To assess the relationship between sociodemographic variables
      (including race, age, and insurance coverage) and preoperative best-corrected
      visual acuity (BCVA) at the time of first-eye cataract surgery. METHODS: Single
      center retrospective chart review study at Shiley Eye Institute, University of
      California, San Diego (UCSD). Medical record data from 600 patients were
      collected from the appointment immediately preceding cataract surgery, including
      BCVA in the operated eye converted to the logarithmic minimal angle of resolution
      (logMAR), insurance coverage, race, sex, age, body mass index, smoking status
      (including pack years), systemic and ocular comorbidities, and ocular surgical
      history. Preoperative BCVA in the operated eye was the main outcome measure.
      RESULTS: Univariate analysis revealed significant differences in BCVA between
      groups by insurance type (public, private, and uninsured), race (Asian, black,
      Hispanic, white, and other), and sex (male and female) (P<0.001, P<0.001, and
      P=0.019, respectively). Further multivariate analysis revealed significant
      pairwise differences, with better BCVA associated with white race (0.85, logMAR
      [Snellen 20/140]) than Hispanic race (1.06, [20/230], P=0.017), and better BCVA
      associated with private insurance (0.79, [20/125]) versus public insurance (0.96,
      [20/180], P=0.0002). CONCLUSION: Hispanic race and public insurance coverage were
      each associated with worse preoperative BCVA compared with white race and private
      insurance, respectively. This suggests that Hispanic race and public insurance
      may predispose patients to decreased access to cataract surgery. Additional
      large, prospective studies are required to rigorously test and elaborate on this
      finding.

PMID- 29369232
TI  - Survey of Ophthalmologists Regarding Practice Patterns for Dry Eye and Sjogren
      Syndrome.
AB  - OBJECTIVE: To survey ophthalmologists about current practice patterns regarding
      the evaluation of dry eye patients and referrals for a Sjogren syndrome (SS)
      workup. METHODS: An online survey was sent to ophthalmologists affiliated with
      the Scheie Eye Institute or Wills Eye Hospital using REDCap in August 2015.
      Descriptive statistics were used to summarize the data. RESULTS: Four hundred
      seventy-four survey invitations were sent out and 101 (21%) ophthalmologists
      completed the survey. The common traditional dry eye test performed was corneal
      fluorescein staining (62%) and the most common newer dry eye test performed was
      tear osmolarity (18%). Half of respondents (51%) refer fewer than 5% of their dry
      eye patients for SS workups, with 18% reporting that they never refer any
      patients. The most common reasons for referrals included positive review of
      systems (60%), severe dry eye symptoms (51%) or ocular signs (47%), or dry eye
      that is refractory to treatment (42%). The majority (83%) felt that there is a
      need for an evidence-based standardized screening tool for dry eye patients to
      decide who should be referred for evaluation for SS. CONCLUSIONS:
      Ophthalmologists continue to prefer the use of traditional dry eye tests in
      practice, with the most common test being corneal fluorescein staining. There is
      an underreferral of dry eye patients for SS workups, which is contributing to the
      continued underdiagnosis of the disease. Most respondents felt that there was a
      need for an evidence-based standardized screening tool to decide which dry eye
      patients should be referred for SS evaluations.

PMID- 29369234
TI  - In Vitro Evaluation of a Hypochlorous Acid Hygiene Solution on Established
      Biofilms.
AB  - OBJECTIVES: The purpose of this study was to determine whether a commercial
      formulation of hypochlorous acid hygiene solution (0.01%), Avenova, can destroy
      existing biofilms formed by ocular clinical bacterial isolates, including
      blepharitis isolates of Staphylococcus aureus and coagulase-negative
      staphylococci, and a keratitis isolate of Pseudomonas aeruginosa. METHODS:
      Biofilms grown in bacterial growth media on disposable contact lens cases were
      challenged with hypochlorous acid hygiene solution. At various time points,
      surviving bacteria were quantified by serial dilution and colony counts.
      Staphylococcus aureus biofilms formed on glass were challenged using a
      hypochlorous acid hygiene solution and imaged using vital staining and confocal
      laser scanning microscopy. RESULTS: Bactericidal activity (>=3 Log10; 99.9%) was
      observed for all tested bacterial species after a 30-min exposure. Staphylococcus
      aureus biofilms had a bactericidal level of killing by 10 min (P<0.01),
      Staphylococcus capitis by 5 min (P<0.001), Staphylococcus epidermidis by 30 min
      (P<0.001), and P. aeruginosa by 10 min (P<0.01). Confocal microscopy and crystal
      violet staining analysis of bacterial biofilms treated with hypochlorous acid
      solution both demonstrated that biofilm bacteria were readily killed, but biofilm
      structure was largely maintained. CONCLUSIONS: Hypochlorous acid (0.01%) hygiene
      solution was able to achieve bactericidal levels of killing of bacteria in
      biofilms but did not disrupt biofilm structures. Susceptibility of tested
      staphylococcal blepharitis isolates varied by species, with S. capitis being the
      most susceptible and S. epidermidis being the least susceptible.

PMID- 29369235
TI  - Global Practice Patterns in the Management of Infantile Cataracts.
AB  - OBJECTIVES: Surveys are an important tool to assess the impact of research on
      physicians' approach to patient care. This survey was conducted to assess current
      practice patterns in the management of infantile cataracts in light of the
      findings of the Infant Aphakia Treatment Study. METHODS: Pediatric
      ophthalmologists were emailed a link to the survey using newsletters from
      American Association of Pediatric Ophthalmology and Strabismus, World Society of
      Pediatric Ophthalmology and Strabismus, and the Pediatric Listserv. The 17
      question survey was anonymous and active during July to August 2016. RESULTS: One
      hundred twenty-five respondents (North America, 65%; Asia, 12%; Europe, 9%; and
      other, 14%) reported operating on pediatric cataracts. Most practice in a
      university setting (55%). There was a strong consensus that unilateral cataract
      surgery should be performed between ages 4 to 6 weeks and aphakic contact lenses
      should be used to optically correct their eyes, particularly in children <=6
      months of age. For bilateral cataracts, there was a trend for surgeons to perform
      cataract surgery at an older age than unilateral cataract surgery. Surgeons who
      performed less than 5 versus greater than 20 pediatric cataract surgeries/year
      were more likely to use aphakic contact lenses in children undergoing cataract
      surgery more than 6 months of age (62% vs. 35%, P=0.04). Most respondents (73%)
      indicated that the Infant Aphakia Treatment Study had changed how they manage
      unilateral congenital cataracts. CONCLUSION: Most pediatric cataract surgeons
      perform congenital cataract surgery between ages 4 to 6 weeks and use aphakic
      contact lenses for initial optical correction in infants less than 6 months.
      Surgeons have equal preference for intraocular lenses and contact lenses in
      infants more than 6 months of age.

PMID- 29369236
TI  - The Impact of Clostridium difficile Infection on Mortality in Patients With
      Inflammatory Bowel Disease.

PMID- 29369238
TI  - To Pull or to Scope: A Prospective Safety and Cost-effectiveness of Percutaneous
      Endoscopic Gastrostomy Tube Replacement Methods.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) tubes are routinely used as
      an effective method for providing enteral nutrition. The need for their exchange
      is common. GOALS: We aimed to examine the comparative safety and cost
      effectiveness of PEG percutaneous counter-traction "pulling" approach or by
      endoscopically guided retrieval. STUDY: A prospective 215 consecutive patients
      undergoing PEG tube insertion were included. Fifty patients in total were
      excluded. The patients were examined for demographics, indications for PEG
      replacement, as well as procedure-related complications and procedural costs.
      RESULTS: Group A included 70 patients (42%) with PEG tubes replaced
      endoscopically, whereas group B included 95 patients (58%) with PEG tubes
      replaced percutaneously. Baselines characteristics were similar between the 2
      groups (P=NS). Group A and group B had similar immediate complication rates
      including 4 patients in group B (4.2%), and 2 patients in group A (2.8%)
      (P=0.24). Complications included a conservatively managed esophageal perforation,
      and self-limited mild bleeding groups A and group B, respectively. The mean
      procedure cost was significantly higher in the endoscopic PEG replacement group
      compared with the percutaneous PEG replacement group ($650 vs. $350,
      respectively). CONCLUSION: Percutaneous PEG replacement appears as safe as
      endoscopic PEG replacement, however, percutaneous tube exchange is less costly.

PMID- 29369237
TI  - Comparative Assessment of Patient Preferences and Tolerability in Barrett
      Esophagus Screening: Results From a Randomized Trial.
AB  - GOALS: To determine patient preference for the Barrett esophagus (BE) screening
      techniques. BACKGROUND: Sedated esophagogastroduodenoscopy (sEGD) and unsedated
      transnasal endoscopy (uTNE) are both potential techniques for BE screening.
      However, systematic assessment of patient preference for these 2 techniques is
      lacking. As part of a comparative effectiveness randomized trial of BE screening
      modalities, we measured short-term patient preferences for the following
      approaches: in-clinic uTNE (huTNE), mobile-based uTNE (muTNE), and sEGD using a
      novel assessment instrument. STUDY: Consenting community patients without known
      BE were randomly assigned to receive huTNE, muTNE, or sEGD, followed by a
      telephone administered preference and tolerability assessment instrument 24 hours
      after study procedures. Patient preference was measured by the waiting trade-off
      method. RESULTS: In total, 201 patients completed screening with huTNE (n=71),
      muTNE (n=71), or sEGD (n=59), and a telephone interview. Patients' preferences
      for sEGD and uTNE using the waiting trade-off method were comparable (P=0.51).
      Although tolerability scores were superior for sEGD (P<0.001) compared with uTNE,
      scores for uTNE examinations were acceptable. CONCLUSIONS: Patient preference is
      comparable between sEGD and uTNE for diagnostic examinations conducted in an
      endoscopy suite or in a mobile setting. Given acceptable tolerability, uTNE may
      be a viable alternative to sEGD for BE screening.

PMID- 29369239
TI  - Rising Events and Improved Outcomes of Gastrointestinal Bleed With Shock in USA:
      A 12-year National Analysis.
AB  - OBJECTIVE: Limited information is available based on single-center studies on
      trends of incidence and outcomes in gastrointestinal (GI) bleed with shock.
      METHODS: We analyzed data from 2002 to 2013 National Inpatient Sample. Using ICD
      9 codes we identified 6.4 million hospital discharges of GI bleed from National
      Inpatient Sample database. Events were analyzed based on type of GI bleed, in
      hospital mortality, hemodynamic status, and use of blood products. RESULTS: GI
      bleed with shock results in higher hospital mortality (20.77% with shock vs. 2.6%
      without shock). Between 2002 and 2013, there has been an increase in the
      percentage of upper and lower GI bleed with shock (1.35% to 4.92% and 1.49% to
      3.06%) along with a reduction in mortality in both upper GI bleed with shock
      (26.9% to 13.8%) and lower GI bleed with shock (54.7% to 19.7%). Consistent with
      the rise in GI bleed with shock was an increase in blood product utilization.
      Packed red blood cell (pRBC) transfusion was associated with reduction in
      mortality in both nonvariceal upper GI bleed with shock (18.3% without pRBC vs.
      13.9% receiving pRBC) and lower GI bleed with shock (36.05% without pRBC vs.
      22.13% receiving pRBC), but did not affect mortality in variceal upper GI bleed
      with shock (31.79% vs. 32.22%). CONCLUSIONS: GI bleed with shock carries a higher
      mortality and have been steadily increasing from 2002 to 2013. pRBC transfusion
      was associated in improved mortality in GI bleed with shock except variceal
      bleed.

PMID- 29369240
TI  - CapsoCam SV-1 Versus PillCam SB 3 in the Detection of Obscure Gastrointestinal
      Bleeding: Results of a Prospective Randomized Comparative Multicenter Study.
AB  - BACKGROUND AND STUDY AIM: Newer capsule with a panoramic viewing mode is
      available and might increase the detection rate of bleeding lesions in patients
      with obscure gastrointestinal bleeding (OGIB). Furthermore, an improved patient
      acceptance rate is expected. MATERIALS AND METHODS: In a randomized prospective
      comparative multicenter study, patients with OGIB were included and examined
      either with CapsoCam SV-1 or with PillCam SB 3. Detection of bleeding lesions,
      transit, and evaluation time and adverse events were evaluated. Physicians were
      interviewed about their experience with both capsules and the evaluation
      software. A detailed subject questionnaire analyzed acceptance of each capsule.
      Follow-up was 3 months. RESULTS: In total, 181 patients with OGIB were recruited
      into the study. After exclusion of 28 patients 153 patients were randomized and
      CapsoCam SV-1 (n=78) or PillCam SB 3 (n=75) was administered. CapsoCam SV-1
      detected more cases of bleeding (31/79, diagnostic yield 39.7%) compared with
      PillCam SB 3 (26/75, diagnostic yield 34.6%, NS). Transit time of both capsules
      was not different. Evaluation time with PillCam SB 3 was superior to CapsoCam SV
      1 (27 vs. 40 min, P=0.01). In total, 95% of the physicians were satisfied with
      each capsule system and evaluation software. The acceptance rate of the patients
      to retrieve the CapsoCam SV-1 was high. Adverse events/serious adverse events
      were 17.9%/1.3% with CapsoCam SV-1 and 16%/0% with PillCam SB 3. Rebleeding rate
      was 28.75% within 3 months. CONCLUSIONS: CapsoCam SV-1 detected more lesions;
      however, relevant bleeding sources were visualized by both capsules. Physician's
      satisfaction was high with both capsule systems and evaluation software.
      Patient's acceptance with CapsoCam SV-1 was unexpectedly high. Serious adverse
      events were 0% with PillCam SB 3 and 1.3% with CapsoCam SV-1.

PMID- 29369241
TI  - Serum Pepsinogen as a Predictor for Gastric Cancer Death: A 16-Year Community
      based Cohort Study.
AB  - GOALS: The purpose of this article is to validate the long-term association
      between initial serum pepsinogen (PG) measurements and subsequent gastric cancer
      specific deaths from a long-term longitudinal cohort. BACKGROUND: Endoscopic
      surveillance can be effective and efficient in reducing gastric cancer mortality
      if a biomarker such as serum PG is available to identify high-risk individuals
      and if the biomarker also is specific to gastric cancer risk. STUDY: Between 1995
      and 1998, a gastric cancer-screening program was conducted in a high-risk
      population: The first stage involved PG testing, and the second stage involved
      upper endoscopy. The outcome was gastric cancer death, which was monitored until
      December 31, 2010; results were expressed as the hazard ratio (HR) and
      corresponding 95% confidence interval (CI) using the Cox proportional hazards
      regression model. Other causes of death were used as comparators. RESULTS: Among
      participants (n=3514) aged >=30 years, 1682 (47.9%) were screened to determine
      serum PG levels. After 16 years of follow-up, 14 deaths from gastric cancer were
      documented. Multivariate analyses adjusted for age, sex, and Helicobacter pylori
      serological positivity showed that PG-I <30 MUg/L and PG-I <30 MUg/L or PG-I/II
      ratio <3 were significantly associated with the risk of gastric cancer death (HR,
      3.27; 95% CI, 1.11-9.61 and HR, 3.45; 95% CI, 1.18-10.12, respectively). In
      contrast, there were no significant associations between PG and other causes of
      death, including neoplastic and non-neoplastic diseases. CONCLUSION: This long
      term cohort study shows the usefulness of PG measurement as a biomarker that is
      specific to the risk of gastric cancer death.

PMID- 29369242
TI  - Long-term Prognosis of Acute-on-Chronic Liver Failure Survivors.
AB  - GOALS: We aimed to investigate significant factors influencing the long-term
      prognosis of patients who survived acute-on-chronic liver failure (ACLF).
      BACKGROUND: The mortality of ACLF is predominantly affected by the organ failure
      severity. However, long-term outcomes of patients who survive ACLF are not known.
      STUDY: A cohort of 1084 cirrhotic patients who survived for more than 3 months
      following acute deterioration of liver function was prospectively followed. ACLF
      was defined by the European Association for the Study of the Liver Chronic Liver
      Failure Consortium definition. RESULTS: The mean follow-up duration was 19.4+/
      9.9 months. In the subgroup of patients without previous acute decompensation
      (AD), ACLF occurrence did not affect long-term outcomes. However, in patients
      with previous AD, ACLF negatively affected long-term transplant-free survival
      even after overcoming ACLF (hazard ratio, 2.00, P=0.012). Previous AD was the
      significant predictive factor of long-term mortality and was independent of the
      Model for End-stage Liver Disease score in these ACLF-surviving patients. Organ
      failure severity did not affect transplant-free survival in patients who survived
      an ACLF episode. CONCLUSIONS: A prior history of AD is the most important factor
      affecting long-term outcomes following an ACLF episode regardless of Model for
      End-stage Liver Disease score. Prevention of a first AD episode may improve the
      long-term transplant-free survival of liver cirrhosis patients.This is an open
      access article distributed under the terms of the Creative Commons Attribution
      Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible
      to download and share the work provided it is properly cited. The work cannot be
      changed in any way or used commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 29369243
TI  - Percutaneous Ultrasound-Guided Musculoskeletal Applications of Autologous Bone
      Marrow Aspirate Concentrate: Preliminary Experience From a Single Institution.
AB  - Emerging musculoskeletal applications for local administration of autologous bone
      marrow aspirate concentrate (BMAC) include treatment of fractures, osteonecrosis,
      osteochondral injuries, osteoarthritis, ligament injury, tendon injury, and
      tendonopathies. Ultrasound-guided technique for various BMAC injection sites is
      detailed in this technical report and our preliminary clinical experience
      outlined.Five patients, 1 woman and 4 men, were treated with 6
      peri/intratendinous (n = 4) or intraarticular (n = 2) BMAC injections between
      July 5, 2015 and December 31, 2016 for the clinical indications of common
      hamstrings origin tendinosis (n = 4), hip labral tear (n = 1), and osteochondral
      lesion of the talus (n = 1).All procedures were technically successful, with BMAC
      locally administered to the therapeutic target and no procedural complications
      observed. Clinical follow-up was available for 5 of 6 procedures. Four of 5
      injections resulted in self-reported symptomatic improvement (clinical follow-up
      range, 2-12 months). One 72-year-old man with right common hamstrings origin
      tendinosis reported no improvement after BMAC injection.The technology is now
      available to support ultrasound-guided, autologous BMAC administration by the
      musculoskeletal interventionalist for common indications. Our initial clinical
      experience is consistent with early reports in the literature. This technique is
      well tolerated by symptomatic patients on an outpatient basis, and rates of self
      reported symptomatic relief are high. Mechanism of action, long-term safety, and
      long-term clinical efficacy remain largely undefined.

PMID- 29369244
TI  - Gastric Lipoma: A Review of the Literature.
AB  - Gastric lipoma is a rare benign tumor of the stomach. The imaging characteristics
      are diagnostic because the lesion has fat attenuation on computed tomography and
      demonstrates characteristics of fat on magnetic resonance images. On ultrasound,
      the lesion can be identified as a lesion hypoechoic to the gastric mucosa that is
      soft, but the mass cannot be displaced with compression. Identifying these
      imaging characteristics can prevent biopsy or surgery in asymptomatic patients.
      Although this lesion is benign, it can cause gastric obstruction.

PMID- 29369245
TI  - Literature Reviews.

PMID- 29369246
TI  - Bowel Ultrasound for the Diagnosis of Necrotizing Enterocolitis: A Meta-analysis.
AB  - Radiographic evaluation for necrotizing enterocolitis (NEC) often yields
      nonspecific findings. Bowel ultrasound (BUS) provides additional information
      beyond that of abdominal radiographs and may be helpful in the diagnosis of NEC
      in neonates. We systematically reviewed and aggregated existing literature to get
      a better estimate of diagnostic accuracy of BUS in the diagnosis of NEC. A
      literature search was performed using PubMed, Embase, and Cumulative Index to
      Nursing and Allied Health Literature to identify studies in which infants with
      clinically suspected NEC were evaluated using BUS. Studies that used modified
      Bell staging criteria as the reference standard were included. Study quality was
      assessed, and pooled sensitivity and specificity of various BUS findings for
      diagnosing NEC were determined. Six articles with a total of 462 patients met
      eligibility and inclusion criteria. There was heterogeneity in BUS findings
      evaluated across studies. Ultrasound detection of classic signs of NEC (portal
      venous gas, pneumatosis, and free air) had pooled sensitivities ranging from 0.27
      to 0.48 and pooled specificities ranging from 0.91 to 0.99. Bowel wall thinning
      and absent peristalsis had overall low sensitivity (0.22 and 0.30) but high
      specificity (0.96 and 0.96) for NEC. Assessment of abdominal fluid, which
      included ascites and focal fluid collection, also had overall low sensitivity and
      high specificity (simple ascites: 0.45 and 0.92; focal fluid collection: 0.19 and
      0.98). In summary, individual BUS findings have low sensitivity and high
      specificity for diagnosis of NEC. Bowel ultrasound may be a useful adjunct to
      plain abdominal radiographs in the evaluation of infants with clinical suspicion
      of NEC.

PMID- 29369247
TI  - Literature Reviews.

PMID- 29369248
TI  - Experience of Using Shear Wave Elastography Imaging in Evaluation of Undescended
      Testes in Children: Feasibility, Reproducibility, and Clinical Potential.
AB  - We aimed to determine the difference in tissue stiffness, which might reflect
      histologic damage, by comparing the potential of the shear wave elastography
      (SWE) values of operated undescended testes (OUT) with those of undescended
      testes (UT) and normal testes. A total of 120 patients (235 testes) were enrolled
      in the current study. Quantitative SWE values were measured by manually drawing
      contours of the entire testis structure with a free region of interest. A group
      of 66 OUT were classified as group A. Operation age and the period passed over
      the operation time and SWE values were compared among the testes assigned to
      group A. The 50 testes having inguinal canal placement were classified as group
      B, and the 119 testes whose sonography findings were normal were classified as
      group C. These 3 groups were compared in terms of the SWE values and volume. The
      SWE values of group A were significantly higher than those of groups B and C (P <
      0.001). The SWE values of group B were significantly higher than those of group C
      (P < 0.001). The SWE values of OUT were significantly higher than those of the
      contralateral normal testes and UT (P < 0.001). There were no significant
      differences among operation age and period passed over the operation time and SWE
      values in the OUT (P > 0.05). There was no significant correlation between SWE
      values and testes' volume (P > 0.05). The SWE technique can be used effectively
      as a new parameter to assess stiffness of the OUT and UT to predict interstitial
      fibrosis and the severity of histologic damage.

PMID- 29369249
TI  - Durable Clinical and Immunologic Advantage of Living Donor Liver Transplantation
      in Children.
AB  - BACKGROUND: Despite high survival in pediatric living donor liver transplantation
      (LDLT), only 10% of liver transplants in children in the United States are from
      living donors, reflecting reluctance to embrace this approach. In addition to
      optimal timing and graft quality, LDLT may offer immunologic benefit because most
      donors are haploidentical parents. We sought to quantify the benefit of LDLT
      compared to deceased donor liver transplantation (DDLT) using granular clinical
      and immunologic outcomes over the long term. METHODS: A retrospective cohort of
      children (age <18 years) surviving 1 year or longer posttransplant was evaluated
      to determine the impact of donor type on graft survival and immunologic outcomes.
      RESULTS: Two hundred forty-one children (177 DDLT and 64 LDLT) were assessed. In
      multivariable analysis, LDLT was associated with a lower rate of acute cellular
      rejection (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.29-0.98; P =
      0.04), a lower rate of chronic rejection (HR, 0.12; 95% CI, 0.03-0.56; P =
      0.007), better graft survival on monotherapy immunosuppression at 3 years
      posttransplant (87.7% vs 46.7%; odds ratio, 7.41; 95% CI, 2.80-19.66; P < 0.001),
      and a lower rate of graft loss (HR, 0.29; 95% CI, 0.10-0.88; P = 0.03). Graft
      type was not an independent predictor of posttransplant mortality (LDLT HR, 0.57;
      95% CI, 0.16-2.01; P = 0.38). Maternal graft LDLT was associated with a lower
      rate of acute cellular rejection (HR, 0.13; 95% CI, 0.03-0.64; P = 0.01) and
      posttransplant lymphoproliferative disorder (HR, 0.04; 95% CI, 0.004-0.44; P =
      0.008) compared with paternal grafts. CONCLUSIONS: This study demonstrates the
      potential benefit of LDLT, particularly with maternal grafts, for pediatric liver
      transplant recipients on multiple clinical parameters over long-term follow-up.

PMID- 29369250
TI  - Public Health in Transitional Vietnam: Achievements and Challenges.

PMID- 29369251
TI  - Community-Based Screening for Cervical Cancer Using Visual Inspection With Acetic
      Acid: Results and Lessons Learned From a Pilot Study in Vietnam.
AB  - CONTEXT: Vietnam still applies the opportunistic cytology-based screening model,
      which failed to have an impact on the increasing burden of cervical cancer in
      Vietnam. OBJECTIVES: To pilot a community-based screening model for cervical
      cancer using visual inspection with acetic acid (VIA) in Vietnam by training
      midwife and assistant physician working at grassroots level of health care
      system. DESIGN: The study employed a pre-experimental design. SETTING: Cases from
      2 provinces of Vietnam. PARTICIPANTS: The study trained 36 assistant
      physicians/midwives working at commune health centers to do VIA screening for
      cervical cancer and provided screening services for 1945 women 30 to 65 years of
      age. INTERVENTION: The pilot intervention had 2 aims: train health care workers
      to do VIA screening and assess the quality of screening services provided by the
      trained staffs by examining the diagnostics value of VIA. RESULTS: All selected
      health care workers were able to perform VIA screening method after training.
      Their VIA services had high diagnostic value: positive predicted value of 11.5%
      and negative predicted value of 99%; for the detection of cervical
      intraepithelial neoplasia (CIN) 2, the sensitivity of VIA is 100%, specificity of
      67.0%, positive predicted value of 5.7%, and negative predicted value of 100%;
      for the detection of CIN 3, the sensitivity of VIA is 100%, specificity of 66.5%,
      positive predicted value of 3.8%, and negative predicted value of 100%. The
      diagnostic value of VIA is comparable with Papanicolaou test but requires far
      fewer resources and suitable with community-based setting. CONCLUSION: Local
      midwives and assistant physicians who currently work at commune health centers
      and district health centers can be trained to do VIA efficiently. Regarding to
      implications for policy and practice, VIA can offer significant advantages over
      Papanicolaou test in low-resource settings like Vietnam, particularly in terms of
      increased screening coverage, improved follow-up care, and overall program
      quality.

PMID- 29369252
TI  - Utilization of Services Provided by Village-Based Ethnic Minority Midwives in
      Vietnam: Lessons From Implementation Research.
AB  - BACKGROUND: Global progress in reducing maternal mortality requires improving
      access to maternal and child health services for the most vulnerable groups. This
      article reports results of implementation research that aimed to increase the
      acceptability of village-based ethnic minority midwives (EMMs) by local
      communities in Vietnam through implementing an integrated interventions package.
      METHODS: The study was carried out in 2 provinces in Vietnam, Dien Bien and Kon
      Tum. A quasi-experimental survey with pretest/posttest design was adopted, which
      included 6 months of intervention implementation. The interventions package
      included introductory "launch" meetings, monthly review meetings at community
      health centers, and 5-day refresher training for EMMs. A mixed-methods approach
      was used involving both quantitative and qualitative data. A structured
      questionnaire was used in the pre- and posttest surveys, complemented by in-depth
      interviews and focus group discussions with EMMs, relatives of pregnant women,
      community representatives, and health managers. RESULTS: Introductions of EMMs to
      their local communities by local authorities and supervision of performance of
      EMMs contributed to significant increases in utilization of services provided by
      EMMs, from 58.6% to 87.7%. Key facilitators included information on how to
      contact EMMs, awareness of services provided by EMMs, and trust in services
      provided by EMMs. The main barriers to utilization of EMM services, which may
      affect sustainability of the EMM scheme, were low self-esteem of EMMs and small
      allowances to EMMs, which also affected the recognition of EMMs in the community.
      CONCLUSIONS: Providing continuous support and integration of EMMs within
      frontline service provision and ensuring adequate local budget for monthly
      allowances are the key factors that should allow sustainability of the EMM scheme
      and continued improvement of access to maternal and child health care among poor
      ethnic minority people living in mountainous areas in Vietnam.

PMID- 29369253
TI  - The Association Between Gender Inequalities and Women's Utilization of Maternal
      Health Services: A Cross-Sectional Survey in Eight South Central Coast Provinces,
      Vietnam.
AB  - BACKGROUND: Gender inequalities influence the utilization of maternal health
      services in Vietnam, but little research has been published. This study,
      therefore, aimed to explore the association between gender inequalities and
      women's utilization of maternal health services in Vietnam. METHODS: The study
      was conducted in 8 provinces in the South Central Coast region of Vietnam during
      August 2013 to May 2014. A total of 907 women who delivered a year prior to the
      date of interview participated in the study. A multiple logistic regression model
      was used to examine the association between gender inequalities (including
      sociodemographic determinants of health) and utilization of 4 or more antenatal
      care (ANC4+) services, institutional delivery, and ever used contraceptive
      methods. RESULTS: The utilization rate of maternal health services was varied,
      from 53.9% for ANC4+ to 87.7% for ever used a contraceptive method and 97% for
      institutional delivery. Ethnicity was identified as the most influential variable
      out of all sociodemographic determinants of health. Regarding gender
      inequalities, couple communication was the only variable having significant
      association with women's utilization of maternal health services. CONCLUSION:
      Women's equal role within context of their daily life and relations with their
      husbands (discussing maternal care with husband and having equal income to
      husband) supported their use of maternal health services. Therefore, there should
      be concerted efforts from all relevant stakeholders including the health system
      to focus on disadvantaged women in planning and delivery of maternal health
      services, especially to ethnic minority women. Male involvement strategy should
      be implemented to promote maternal health care, especially during the prenatal
      and postpartum period. To provide more culturally sensitive and right-based
      approaches in delivery of maternal health services to disadvantaged women in
      Vietnam, interventions are recommended that promote male involvement, that is, to
      engage men in service delivery to adapt and ensure the most appropriate and
      effective maternal health care.

PMID- 29369254
TI  - Community Participatory Interventions to Improve Farmer Knowledge and Practices
      of Household Biogas Unit Operation in Ha Nam Province, Vietnam.
AB  - CONTEXT: The use of biogas systems to treat livestock waste is a common practice
      in Vietnam. However, farmers' knowledge and practices of the safe and appropriate
      use of household biogas units (HBUs) are still limited and could negatively
      impact human, animal, and environmental health. OBJECTIVE: To assess the
      effectiveness of an intervention to improve knowledge and practices of biogas
      operation among farmers in 2 communes of Ha Nam Province, Vietnam. DESIGN: A
      community-based intervention approach. SETTING: This study was conducted from
      2015 to 2016 in 2 communes of Ha Nam Province, Vietnam. PARTICIPANTS: Only
      farmers with HBUs (N = 399) participated in this research. Farmers were assigned
      to either an intervention group or a control group at a ratio of 1:2.
      INTERVENTION: Two intervention steps were implemented over a 6-month period as
      follows: (i) the core farmer group trained in 6 steps of HBU safe handling
      practice; and (ii) the core farmer group conducted peer-to-peer communication
      with its neighbors in the commune using the provided material. MAIN OUTCOME
      MEASURE(S): Farmers' knowledge and practices in biogas operation were assessed by
      a structured questionnaire. The questionnaire was administered before (baseline)
      and after the intervention (follow-up) to both the control and intervention
      groups. RESULTS: There was a significant difference in the knowledge and
      practices of biogas operation between the 2 groups, in which farmers in the
      intervention group demonstrated better understanding of the related topic than
      the control group (P < .05, t test). A linear regression model indicated that
      baseline and follow-up scores in both knowledge and practices of the intervention
      group were higher than those of the control group. After the intervention, the
      mean difference score in knowledge and practices between the intervention and
      control groups was 5.0 and 2.0 points, respectively (P < .01). CONCLUSION: A
      community-based intervention approach could be applied to improve knowledge and
      practices among farmers in using biogas systems. However, further studies should
      be conducted to assess the sustainability and effectiveness of this model.

PMID- 29369255
TI  - Evaluation of an Ecohealth Approach to Public Health Intervention in Ha Nam,
      Vietnam.
AB  - CONTEXT: Ecohealth is a transdisciplinary research approach that considers socio
      economic, cultural, and environmental factors. Ecohealth program assessment is
      sometimes unable to capture the process of change, especially when the evidence
      is not well documented. As such, there is a need to better understand how
      ecohealth approaches are understood, integrated, and adapted in practice to
      support the sustainability of the approach. OBJECTIVE: To evaluate the use of an
      ecohealth approach to a community-based intervention to improve environmental
      sanitation and draw lessons learned for similar public health initiatives.
      DESIGN: An iterative evaluation approach involving 27 in-depth interviews and 9
      focus group discussions was used to gather feedback on the intervention
      activities and outcomes from all participants. SETTING AND PARTICIPANTS: The
      study site was Hoang Tay commune, Kim Bang district, Ha Nam province. The
      participants included 12 farmers, 4 local policy makers, and 7 researchers from
      Hanoi University of Public Health. RESULTS: The farmers provided specific
      shortcomings of the biogas procedure steps, while the local authorities
      identified new and more effective ways to promote sanitation guidelines.
      Outcomes, as behavior changes, in 3 participant groups were captured. CONCLUSION:
      Participation in ecohealth interventions should be collegial to give
      opportunities for all related stakeholders to build capacity, support, and
      achieve the transdisciplinary principle. This also helps ensure that the
      community-based solutions are incorporated in public health interventions.
      Participatory monitoring and evaluation should support the understanding of the
      implementation process to capture intervention outcomes.

PMID- 29369256
TI  - Injury Mortality in Vietnam: Patterns and Trends, 2005-2013.
AB  - CONTEXT: Injury is a growing public health problem worldwide. Deaths due to
      injuries account for 10% of the world's mortality. More than 90% of the world's
      injury-related deaths occur in low- and middle-income countries such as Vietnam.
      The public health burden has been recognized by government; however, there is a
      need to study and better understand the epidemiology and trends for injuries and
      injury-related mortality to be able to better address this burden. OBJECTIVES: In
      this article, we analyze the patterns and trends in injury mortality from 2005 to
      2013 in Vietnam. DESIGN: All registered deaths from injuries from January 2005 to
      December 2013 were extracted from the Ministry of Health death recording system
      (A6). Mortality rates per 100 000 population per year were calculated. A linear
      regression model was used to estimate the injury mortality trends. RESULTS: In
      the 9-year period, 313 101 deaths due to injuries were recorded in the A6 system;
      this accounts for about 10% of all deaths. The leading causes of injury-related
      death were road traffic injuries among the entire population, while drowning was
      the leading cause of death among children. Other unintentional injuries including
      occupational, fall, poisoning, and exposure to electric current also accounted
      for a substantial proportion of the burden of injury. There is a significant
      reduction trend found in drowning among children 0 to 18 years of age and
      significant increasing trends in intentional injury causes. CONCLUSIONS: While
      injuries have been recognized as a public health problem in Vietnam in the last
      decade, as seen by our analysis, there is a need for concerted action to reduce
      their burden. Of particular concern is the increasing prominence of intentional
      injuries. Improved data systems, increasing the awareness in the community, and
      making appropriate policies and implementing them, as well as implementing
      effective, evidence-based interventions are all key to decreasing this burden.
      This is an important study describing injury mortality in Vietnam for the period
      2005-2013. The results of the study show that injury death remains an important
      public health issue that needs more attention from government and relevant
      agencies.

PMID- 29369257
TI  - Universal Health Insurance Coverage in Vietnam: A Stakeholder Analysis From
      Policy Proposal (1989) to Implementation (2014).
AB  - CONTEXT: In 1989, health insurance (HI) was introduced in Vietnam and began to be
      implemented in 1992. There was limited progress until the 2014 Law on HI that was
      revised with the aim of universal health insurance coverage (UHIC) by 2020. This
      article explores stakeholder roles and positions from the initial introduction of
      HI to the implementation of the Master Plan accelerating UHIC. OBJECTIVE: To
      better understand the influence of stakeholders in accelerating UHIC to achieve
      equity in health care. DESIGN: Using a qualitative study design, we conducted
      content analysis of HI-related documents and interviewed social security and
      health system key informants, government representatives, and community
      stakeholders to determine their positions and influence on UHIC. RESULTS: Our
      findings demonstrate different levels of support of stakeholders that influence
      in the HI formulation and implementation, from opposition when HI was first
      introduced in 1989 to collaboration of stakeholders from 2013 when the Master
      Plan for UHIC was implemented. Despite an initial failure to secure the support
      of the Parliament for a Law on HI, a subsequent series of alternative legislative
      strategies brought limited increases in HI coverage. With government financial
      subsidization, the involvement of multiple stakeholders, political commitment,
      and flexible working mechanisms among stakeholders have remained important, with
      an increasing recognition that HI is not only a technical aspect of the health
      system but also a broader socioeconomic and governance issue. The different
      levels of power and influence among stakeholders, together with their commercial
      and political interests and their different perceptions of HI, have influenced
      stakeholders' support or opposition to HI policies. CONCLUSIONS: Despite high
      level policy support, stakeholders' positions may vary, depending on their
      perceptions of the policy implications. A shift in government stakeholder
      positions, especially at the provincial level, has been necessary to accelerate
      UHIC progress and build institutional capacity.

PMID- 29369258
TI  - Health Service Utilization Among People With Noncommunicable Diseases in Rural
      Vietnam.
AB  - CONTEXT: Chronic noncommunicable diseases (NCDs) have been shown to be major
      causes of morbidity and mortality in hospitals for the whole country. OBJECTIVE:
      This study aims to describe the situation of health service utilization among
      people with NCDs in a rural area and identify association between the situation
      of health service utilization among people with chronic diseases and their
      socioeconomic status. DESIGN: This was a cross-sectional study. SETTING: A rural
      district located in the North of Vietnam. PARTICIPANTS: People 15 years of age
      and older. Health service utilization was analyzed only among people who reported
      having NCD. MAIN OUTCOME MEASURES: Data were collected through a personal
      household interview conducted by 12 trained field workers. The dependent variable
      is health care service utilization among people with chronic NCDs. The
      explanatory variables include both household attributes such as household
      economic conditions, and so forth, and individual characteristics. RESULTS:
      Eighteen percent of the adults and 51% of the elderly respondents reported having
      at least 1 of the NCDs. The proportions of people with NCDs who used at least 1
      outpatient service and used at least 1 inpatient health service during the last
      12 months were 68.1% and 10.7%, respectively (the nonutilization rates of 31.9%
      and 89.3%, respectively). The statistically significant correlates of health care
      service utilization among people with NCDs were ethnicity (ethnic minority was
      significantly associated with a lower odds of health care service utilization)
      and health insurance (no health insurance was significantly associated with lower
      odds of health care service utilization). CONCLUSION: Given the evidence from
      this study, actions to improve access to health care services among people with
      NCDs are clearly needed. The capacity of primary health care system for the
      prevention and control of NCDs should be ranked a top priority.

PMID- 29369259
TI  - Alcohol Consumption and Binge Drinking Among Adult Population: Evidence From the
      CHILILAB Health and Demographic Surveillance System in Vietnam.
AB  - CONTEXT: Alcohol contributes to severe social and health problems and is a major
      risk factor for noncommunicable diseases in Vietnam. Over the years, there has
      been an increase in consumption per capita as well as a rapid expansion of
      commercially prepared alcohol. OBJECTIVE: To describe the prevalence of alcohol
      consumption and binge drinking in a random sample of people 15 years of age and
      older living in Chi Linh who were also a part of the Chi Linh Health and
      Demographic Surveillance System (CHILILAB HDSS) and to determine the association
      between alcohol use and sociodemographic characteristics. DESIGN: Data on alcohol
      consumption of 5438 people 15 years of age and older were extracted from the
      CHILILAB HDSS information collected in 2016. Descriptive statistics and multiple
      logistic regression were utilized to assess the association between current
      drinkers and binge drinkers with socioeconomic groups. RESULTS: The overall
      prevalence of alcohol use 1 month prior to interview was 41.1%, which is composed
      of 75.1% males and 17.3% females. Among the 41% of alcohol drinkers, 31.7%
      reported binge drinking over the last 30 days. The proportion of binge drinking
      was also found to be higher among males than among females. The association
      between current drinkers, binge drinkers and gender, area of residence,
      education, and family income level was statistically significant. CONCLUSIONS:
      This study confirms that alcohol use among current and binge drinkers is common
      among males in Vietnam and that it is also a rising issue among females. Alcohol
      use is also associated with sociodemographic factors and income level. The
      results of this study provide evidence of harmful alcohol use among the
      Vietnamese population, which could help policy makers further advocate for the
      approval of the Vietnamese alcohol harm reduction law in the coming years. The
      results of this study reaffirm the need for public health strategies, including
      the formulation of laws and policies to reduce the harmful effects of alcohol
      consumption in Vietnam.

PMID- 29369260
TI  - Strengthening Public Health Management Capacity in Vietnam: Preparing Local
      Public Health Workers for New Roles in a Decentralized Health System.
AB  - Health sector decentralization has created an urgent need to strengthen public
      health management capacity in many countries throughout the developing world.
      This article describes the establishment of a national management training
      network in Vietnam that used Project-Based Learning to strengthen management
      competencies of HIV program workers and linked training to measurable improvement
      in HIV/AIDS public health program outcomes. Skills were taught using a
      combination of classroom learning and mentored fieldwork. From 2005 to 2015, 827
      HIV/AIDS program managers were trained with this method throughout Vietnam by
      trainers in 3 regional training centers. A total of 218 applied learning projects
      were carried out by trainees during this period; 132 resulted in measurable
      improvements in HIV/AIDS program outputs, and 86 produced well-organized plans
      for implementing, monitoring, and evaluating HIV/AIDS intervention strategies.
      Vietnam's management training network represents an important advancement in
      public health workforce development that helps prepare workers for new roles and
      responsibilities in a decentralized health system.

PMID- 29369261
TI  - Screening of Pediatric Facial Fractures by Brain Computed Tomography: Diagnostic
      Performance Comparison With Facial Computed Tomography.
AB  - OBJECTIVES: Facial bone fractures secondary to head trauma are more common in
      children than in adults. Recently, multidetector row computed tomography (CT) has
      been considered superior to conventional radiography. Some studies have reported
      that facial soft tissue injuries require both facial and brain CT and that brain
      CT is helpful in screening facial bone fractures. However, these studies included
      only adult patients. The aim of this study was to evaluate the diagnostic
      performance of brain CT and the need for additional facial CT to detect facial
      bone fractures in emergency pediatrics. METHODS: This multicenter study was
      conducted retrospectively in 2 tertiary hospitals in Seoul, Republic of Korea.
      The data were collected from the medical records of pediatric patients younger
      than 8 years who had undergone both brain and facial CT on the same day in the
      emergency department. All CT scans were retrospectively and independently
      evaluated by 1 board-certified radiologist and 1 board-certified emergency
      medicine physician. A P value of <0.05 was considered statistically significant.
      RESULTS: Sensitivity was 92.31%, specificity was 100%, positive predictive value
      was 100%, negative predictive value was 99.31%, and accuracy was 99.36% for the
      emergency physician; all parameters were 100% for the radiologist. CONCLUSIONS:
      Brain CT showed high diagnostic performance to detect facial bone fractures with
      high accuracy in pediatric patients. As emergency physicians, we should consider
      facial bone fractures when reviewing brain CT images of pediatric patients with
      blunt head and face trauma.

PMID- 29369263
TI  - Do You C What I C: Emergency Department Evaluation and Diagnosis of Pediatric
      Scurvy in an Autistic Child With a Restricted Diet.
AB  - Scurvy in modern times may not be as rare as previously thought. The link between
      adequate intake of vitamin C and scurvy has been known since ancient times and is
      recorded in Ebers Papyrus. Recent reports indicate that, with restricted diets,
      vitamin C deficiency is being seen in infants exclusively fed plant-based formula
      and children with oral aversion, autism, restricted diets, and cerebral palsy.
      Additional at-risk groups include the older adults and patients having
      alcoholism. Often costly, emergency department visits and elaborate diagnostic
      studies lead to fruitless results when a simple diet history is often overlooked.
      Here, we report a case of pediatric scurvy in an 11-year-old autistic child with
      a restricted diet who presented with refusal to walk, fatigue, a purpuric rash,
      and gingival bleeding. The diagnosis was made based on diet history, physical
      examination findings, and symptom resolution with vitamin C supplementation. Our
      case report reaffirms that vitamin C deficiency still occurs and should be
      considered in children with restrictive diets. Early recognition of this disease
      by physicians provides early diagnosis, avoids costly diagnostic workup and
      hospitalization, and expedites effective treatment.

PMID- 29369262
TI  - Analysis of Complications After Button Battery Ingestion in Children.
AB  - AIM: Button battery ingestion (BBI) in children may cause severe complications.
      This analysis is a literature review of complications after pediatric BBI.
      METHODS: Literature was searched on PubMed (1995-2015) using the terms "button
      battery," "ingestion," and "children." End points were age, type and diameter of
      battery, complications, affected organ, and fatality. RESULTS: A total of 31
      publications were analyzed. Patients from 4 months to 19 years old were included
      (n = 136,191, with n = 102,143 or 75% aged <6 y). In 6262, the diameter of the
      battery was documented. Batteries of 20 mm or greater in size were more prone to
      complications (n = 226). With regard to the anatomy, BBI caused complications
      mainly in the esophagus (n = 88, 38.94%). Sixty-one fatal outcomes were reported.
      CONCLUSIONS: Children younger than 6 years are the most prone to BBI, with
      lithium batteries of 20 mm or greater in size associated with complications.
      Complications have been estimated at 0.165%, with lethality of 0.04%. The
      esophagus is the most affected organ, but vascular involvement is often fatal.

PMID- 29369264
TI  - Endoscopic Findings Associated With Button Battery Ingestion in Children: Do We
      Need to Change the Protocol for Managing Gastric Location?
AB  - BACKGROUND: Ingested button batteries (BB) can cause corrosive damage of
      digestive mucosa within minutes. Immediate endoscopic removal of esophageal BB
      has been clearly established, but the management of BB located in the stomach is
      still controversial. AIM: To describe demographic, clinical, radiologic, and
      endoscopic characteristics of a series of pediatric patients evaluated for BB
      ingestion. METHODS: Retrospective analysis of clinical charts belonging to
      children younger than 15 years, who underwent endoscopic removal of BB at Clinica
      Alemana of Santiago, between November 2007 and November 2011. RESULTS: Twenty
      five patients subjected to upper endoscopy were analyzed; median age, 31 months;
      15 were male (60%), and 11 patients (46%) were symptomatic after ingestion. The
      BB ingestion was confirmed by radiograph. Endoscopy revealed 10 patients with BB
      in the esophagus, 12 patients in the stomach and 3 distal to duodenum. Range time
      between ingestion and endoscopy was 2 to 10 hours for esophageal BB and 2 hours
      to 3 days for gastric BB. Eight of the 22 BBs removed had a diameter of 20 mm or
      greater, 6 of them were located in the esophagus and 2 in stomach. The BB color
      changes were observed in 14 of the 22 BBs. Breakage of battery edges was present
      in 11 of the 22 batteries. All patients with esophageal BB and 6 of those 12 with
      gastric BB presented mucosal damage. CONCLUSION: Esophageal BB cause damage
      within hours. The BB located in the stomach may also cause damage early.
      Extraction of gastric BB before 48 hours should be considered.

PMID- 29369265
TI  - A Provider-Focused Intervention to Promote Optimal Care of Pediatric Patients
      With Suspected Elbow Fracture.
AB  - OBJECTIVE: Emergency department (ED) and urgent care (UC) physicians' accurate
      assessment of the neurovascular and musculoskeletal (NV/MSK) examination in
      pediatric patients with suspected elbow fracture is crucial to the early
      recognition of neurovascular compromise. Our objective was to determine the
      impact of computer-based simulation (CBS) and computerized clinical decision
      support systems (CCDSS) on ED and UC physicians' assessment of the NV/MSK
      examination of pediatric patients with elbow fracture as noted in their
      documentation. METHODS: All ED UC physician participants received CBS training
      about management of pediatric patients with suspected elbow fracture.
      Participants were then randomized to receive CCDSS (intervention arm) when an
      eligible patient was seen or no further intervention (comparison arm.)
      Participants received feedback on the proportion of patients with discharge
      diagnosis of elbow fracture with proper examination elements documented. RESULTS:
      Twenty-eight ED and UC physicians were enrolled - 14 in each arm. Over the span
      of 16 weeks, 50 patients with a discharge diagnosis of elbow fracture were seen -
      25 in each arm. Twenty-two of 25 (88%) patients seen by intervention arm
      participants had a complete NV/MSK examination documented. Six of 25 (24%)
      patients seen by comparison arm participants had a complete NV/MSK examination
      documented. Elements most commonly missed in the comparison arm included
      documentation of ulnar pulse as well as radial, median, and ulnar nerve motor
      functions. CONCLUSIONS: Compared with single CBS training alone, repeated
      exposure to CCDSS after CBS training resulted in improved documentation of the
      NV/MSK status of pediatric patients with elbow fracture.

PMID- 29369266
TI  - Pain Intensity and Risk of Bone Fracture in Children With Minor Extremity
      Injuries.
AB  - OBJECTIVES: Injuries are one of the most common causes of pediatric emergency
      department (ED) visit. The aim of this study was to investigate the relationship
      between the intensity of pain at the ED visit of children presenting with an
      extremity injury and the risk of fracture. METHODS: We conducted a retrospective
      study, considering all patients presenting to the ED of a children's hospital in
      Italy, with an accidental extremity injury, between May and December 2015. We
      selected all children aged 8 to 17 years who underwent an x-ray. Children with
      major, multiple, or nonextremity injuries were excluded. Age, sex, spontaneous
      and palpation pain, local swelling, time between injury, and medical evaluation
      were recorded. Sensibility and specificity of spontaneous and palpation pain in
      detecting a fracture were calculated. RESULTS: We reviewed 994 medical records;
      of these, 344 (34.6%) reported a fracture. Children's median age was 12 years
      (interquartile range [IQR], 10-14). Median spontaneous pain at the ED visit was
      not significantly different between children with and without a fracture: 4.0
      (1.0-6.0) and 5 (1.0-6.0), respectively (P = 0.129). Children with mild palpation
      pain and children without an increase of pain of at least 2 points between
      spontaneous and palpation pain were fractured in 3.2% and 0.97% of cases,
      respectively. CONCLUSIONS: In this series, pain intensity in children with a
      minor extremity injury was not a good marker of fracture. Nevertheless, children
      with mild palpation pain or with a mild increase of pain between spontaneous and
      palpation pain had a low risk of fracture.

PMID- 29369267
TI  - Advancing Professional Development Through a Community of Practice: the New
      England Network for Faculty Affairs.
AB  - INTRODUCTION: In an era of competing priorities, funding is increasingly
      restricted for offices of faculty affairs and development. Opportunities for
      professional staff to grow and network through attendance at national meetings
      and to share best practices are limited. We sought to describe a community of
      practice established to enhance the professional development of faculty affairs
      professionals and to document its impact. METHODS: We outlined the process of
      formation of the New England Network for Faculty Affairs (NENFA), reviewed the
      pedagogical approaches to professional development, and surveyed members to
      evaluate the impact of NENFA on their activities, professional network and their
      institutions. RESULTS: After a successful 2011 initial meeting, NENFA created an
      organizing committee and conducted a needs assessment among potential members.
      NENFA's charter, mission, goals, and structure were based on survey results.
      NENFA's regional community of practice grew to 31 institutions and held 10
      meetings over 5 years. Meetings have examined a faculty development topic in
      depth using multiple learning formats to engage participants from academic
      medical centers and allied professions. Results from a 2015 member survey
      confirmed the value of NENFA. Multiple members documented changes in practice as
      a result of participating. DISCUSSION: NENFA has been sustained by volunteer
      leadership, collaboration, and the value that the group has brought to its
      members. We propose that a "community of practice" offers an effective model for
      collaborative learning among individuals at different institutions within a
      competitive health care environment. We recommend that the approach be replicated
      in other regions.

PMID- 29369268
TI  - Innovative Multimodal Training Program for Family Physicians Leads to Positive
      Outcomes Among Their HIV-Positive Patients.
AB  - CME programs can increase physicians' uptake and adherence to clinical guidelines
      for chronic diseases. We developed an intensive multimodal training program for
      family physicians to increase their competency in the management and treatment of
      HIV, through group learning and via close interactions with expert clinicians in
      HIV. We trained 51 physicians from September 2010 to June 2015 and compared their
      adherence to clinical guidelines 1 year before and 1 year after the program. We
      observed significant increases in the physicians' HIV-related clinical
      competencies, in accordance with clinical guidelines, and an increase in the
      number of HIV-positive patients seen by these physicians and the number of
      combination antiretroviral therapies prescribed by these physicians. By combining
      various pedagogical approaches, as well as creating and encouraging communities
      of practice, we were able to make a durable impact on physician performance and
      patient-specific outcomes.

PMID- 29369269
TI  - Developing a Web Platform to Support a Community of Practice: A Mixed Methods
      Study in Pediatric Physiotherapy.
AB  - INTRODUCTION: Web platforms are increasingly used to support virtual interactions
      between members of communities of practice (CoP). However, little is known about
      how to develop these platforms to support the implementation of best practices
      for health care professionals. The aim of this article is to explore pediatric
      physiotherapists' (PTs) perspectives regarding the utility and usability of the
      characteristic of a web platform developed to support virtual communities of
      practice (vCoP). METHODS: This study adopted an explanatory sequential mixed
      methods design. A web platform supporting the interactions of vCoP members was
      developed for PTs working with children with developmental coordination disorder.
      Specific strategies and features were created to support the effectiveness of the
      platform across three domains: social, information-quality, and system-quality
      factors. Quantitative data were collected from a cross-sectional survey (n = 41)
      after 5 months of access to the web platform. Descriptive statistics were
      calculated. Qualitative data were also collected from semistructured interviews
      (n = 9), which were coded, interpreted, and analyzed by using Boucher's Web
      Ergonomics Conceptual Framework. RESULTS: The utility of web platform
      characteristics targeting the three key domain factors were generally perceived
      positively by PTs. However, web platform usability issues were noted by PTs,
      including problems with navigation and information retrieval. DISCUSSION: Web
      platform aiming to support vCoP should be carefully developed to target potential
      users' needs. Whenever possible, users should co-construct the web platform with
      vCoP developers. Moreover, each of the developed characteristics (eg, newsletter,
      search function) should be evaluated in terms of utility and usability for the
      users.

PMID- 29369270
TI  - Letters.

PMID- 29369272
TI  - Care coordination at end of life: The nurse's role.

PMID- 29369273
TI  - Global convergence of emerging infectious diseases: Only a plane ride away.

PMID- 29369274
TI  - Motivational interviewing for patients with mood disorders.

PMID- 29369275
TI  - Practical tips for novice nurse educators.

PMID- 29369279
TI  - Handle with care: Caring for children with autism spectrum disorder in the ED.

PMID- 29369280
TI  - Protect older adults from polypharmacy hazards.

PMID- 29369281
TI  - A pilot study exploring rehabilitation nurses' perceptions of 12-hour shifts.

PMID- 29369282
TI  - Why your facility needs a full-time certified wound care nurse.

PMID- 29369283
TI  - Early pushing urge in the laboring patient.

PMID- 29369284
TI  - Apps for nurses.

PMID- 29369286
TI  - One hospital's journey to create a sustainable sepsis program.

PMID- 29369287
TI  - Guest Editorial: Background and Rationale for Clinical Trial Registration.

PMID- 29369288
TI  - Developmental Effects in Masking Release for Speech-in-Speech Perception Due to a
      Target/Masker Sex Mismatch.
AB  - OBJECTIVES: The purpose of this study was to evaluate the extent to which
      infants, school-age children, and adults benefit from a target/masker sex
      mismatch in the context of speech detection or recognition in a background of 2
      competing talkers. It was hypothesized that the ability to benefit from a
      target/masker sex mismatch develops between infancy and the early school-age
      years, as children gain listening experience in multi-talker environments.
      DESIGN: Listeners were infants (7 to 13 months), children (5 to 10 years), and
      adults (18 to 33 years) with normal hearing. A series of five experiments
      compared speech detection or recognition in continuous two-talker speech across
      target/masker conditions that were sex matched or sex mismatched. In experiments
      1 and 2, an observer-based, single-interval procedure was used to estimate speech
      detection thresholds for a spondaic word in a two-talker speech masker. In
      experiments 3 and 4, speech recognition thresholds were estimated in continuous
      two-talker speech using a four-alternative, forced-choice procedure. In
      experiment 5, speech reception thresholds (SRTs) were estimated for adults using
      the forced-choice recognition procedure after ideal time-frequency segregation
      processing was applied to the stimuli. RESULTS: Speech detection thresholds for
      adults tested in experiments 1 and 2 were significantly higher when the target
      word and speech masker were matched in sex than when they were mismatched, but
      thresholds for infants were similar across sex-matched and sex-mismatched
      conditions. Results for experiments 3 and 4 showed that school-age children and
      adults benefit from a target/masker sex mismatch for a forced-choice word
      recognition task. Children, however, obtained greater benefit than adults in 1
      condition, perhaps due to greater susceptibility to masking overall. In
      experiment 5, adults had substantial threshold reductions and more uniform
      performance across the 4 conditions evaluated in experiments 3 and 4 after the
      application of ideal time-frequency segregation to the stimuli. CONCLUSIONS: The
      pattern of results observed across experiments suggests that the ability to take
      advantage of differences in vocal characteristics typically found between speech
      produced by male and female talkers develops between infancy and the school-age
      years. Considerable child-adult differences in susceptibility to speech-in-speech
      masking were observed for school-age children as old as 11 years of age in both
      sex-matched and sex-mismatched conditions.

PMID- 29369289
TI  - Celebrating 45 Years of American Audiology Society Excellence: Memoirs of a
      Founder.

PMID- 29369291
TI  - Editorial: Clinical Trial Registration-Ear and Hearing Policy.

PMID- 29369290
TI  - Longitudinal Development of Distortion Product Otoacoustic Emissions in Infants
      With Normal Hearing.
AB  - OBJECTIVES: The purpose of this study was to describe normal characteristics of
      distortion product otoacoustic emission (DPOAE) signal and noise level in a group
      of newborns and infants with normal hearing followed longitudinally from birth to
      15 months of age. DESIGN: This is a prospective, longitudinal study of 231
      infants who passed newborn hearing screening and were verified to have normal
      hearing. Infants were enrolled from a well-baby nursery and two neonatal
      intensive care units (NICUs) in Cincinnati, OH. Normal hearing was confirmed with
      threshold auditory brainstem response and visual reinforcement audiometry. DPOAEs
      were measured in up to four study visits over the first year after birth.
      Stimulus frequencies f1 and f2 were used with f2/f1 = 1.22, and the DPOAE was
      recorded at frequency 2f1-f2. A longitudinal repeated-measure linear mixed model
      design was used to study changes in DPOAE level and noise level as related to
      age, middle ear transfer, race, and NICU history. RESULTS: Significant changes in
      the DPOAE and noise levels occurred from birth to 12 months of age. DPOAE levels
      were the highest at 1 month of age. The largest decrease in DPOAE level occurred
      between 1 and 5 months of age in the mid to high frequencies (2 to 8 kHz) with
      minimal changes occurring between 6, 9, and 12 months of age. The decrease in
      DPOAE level was significantly related to a decrease in wideband absorbance at the
      same f2 frequencies. DPOAE noise level increased only slightly with age over the
      first year with the highest noise levels in the 12-month-old age range. Minor,
      nonsystematic effects for NICU history, race, and gestational age at birth were
      found, thus these results were generalizable to commonly seen clinical
      populations. CONCLUSIONS: DPOAE levels were related to wideband middle ear
      absorbance changes in this large sample of infants confirmed to have normal
      hearing at auditory brainstem response and visual reinforcement audiometry
      testing. This normative database can be used to evaluate clinical results from
      birth to 1 year of age. The distributions of DPOAE level and signal to noise
      ratio data reported herein across frequency and age in normal-hearing infants who
      were healthy or had NICU histories may be helpful to detect the presence of
      hearing loss in infants.

PMID- 29369292
TI  - The contribution of family history to the burden of diagnosed diabetes,
      undiagnosed diabetes, and prediabetes in the United States: analysis of the
      National Health and Nutrition Examination Survey, 2009-2014.
AB  - PURPOSE: Given the importance of family history in the early detection and
      prevention of type 2 diabetes, we quantified the public health impact of reported
      family health history on diagnosed diabetes (DD), undiagnosed diabetes (UD), and
      prediabetes (PD) in the United States. METHODS: We used population data from the
      National Health and Nutrition Examination Survey 2009-2014 to measure the
      association of reported family history of diabetes with DD, UD, and PD. RESULTS:
      Using polytomous logistic regression and multivariable adjustment, family history
      prevalence ratios were 4.27 (confidence interval (CI): 3.57, 5.12) for DD, 2.03
      (CI: 1.56, 2.63) for UD, and 1.26 (CI: 1.09, 1.44) for PD. In the United States,
      we estimate that 10.1 million DD cases, 1.4 million UD cases, and 3.9 million PD
      cases can be attributed to having a family history of diabetes. CONCLUSION: These
      findings confirm that family history of diabetes has a major public health impact
      on diabetes in the United States. In spite of the recent interest and focus on
      genomics and precision medicine, family health history continues to be an
      integral component of public health campaigns to identify persons at high risk
      for developing type 2 diabetes and early detection of diabetes to prevent or
      delay complications.

PMID- 29369293
TI  - CardioClassifier: disease- and gene-specific computational decision support for
      clinical genome interpretation.
AB  - PURPOSE: Internationally adopted variant interpretation guidelines from the
      American College of Medical Genetics and Genomics (ACMG) are generic and require
      disease-specific refinement. Here we developed CardioClassifier (
      http://www.cardioclassifier.org ), a semiautomated decision-support tool for
      inherited cardiac conditions (ICCs). METHODS: CardioClassifier integrates data
      retrieved from multiple sources with user-input case-specific information,
      through an interactive interface, to support variant interpretation. Combining
      disease- and gene-specific knowledge with variant observations in large cohorts
      of cases and controls, we refined 14 computational ACMG criteria and created
      three ICC-specific rules. RESULTS: We benchmarked CardioClassifier on 57 expertly
      curated variants and show full retrieval of all computational data, concordantly
      activating 87.3% of rules. A generic annotation tool identified fewer than half
      as many clinically actionable variants (64/219 vs. 156/219, Fisher's P = 1.1  * 
      10-18), with important false positives, illustrating the critical importance of
      disease and gene-specific annotations. CardioClassifier identified putatively
      disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with
      leading ICC laboratories. Through addition of manually curated data, variants
      found in over 40% of cardiomyopathy cases are fully annotated, without requiring
      additional user-input data. CONCLUSION: CardioClassifier is an ICC-specific
      decision-support tool that integrates expertly curated computational annotations
      with case-specific data to generate fast, reproducible, and interactive variant
      pathogenicity reports, according to best practice guidelines.

PMID- 29369294
TI  - Developmental neurotoxicants and the vulnerable male brain: a systematic review
      of suspected neurotoxicants that disproportionally affect males.
AB  - The prevalence of neurodevelopmental disorders (NDs), including autism spectrum
      disorder, attention-deficit/hyperactivity disorder, tic disorder, obsessive
      compulsive disorder, and emotional disturbances, has increased notably in the
      past few decades. To date, debate continues as to the origins of NDs. Increases
      in widespread exposure to and bioaccumulation of chemical neurotoxicants have
      paralleled the upsurge in NDs, and are suggested to be causal agents for NDs. One
      consistent aspect of NDs is the male preponderance. This review considers the
      issue of male preponderance by reviewing the gender-specific neurotoxic effects
      of recognized neurotoxicant chemicals to assess their possible etiology in NDs.
      This investigation consisted of a systematic literature review of original
      studies published from 1970-2016 on suspected neurotoxicants, to examine whether
      they have a disproportionate adverse effect based on gender. Based on that
      review, the neurotoxicants exhibiting consistent gender-specific effects, with
      exposed males being more affected (than similarly exposed females), were: lead,
      Thimerosal/ethylmercury, some organochlorine pesticides (e.g., dieldrin,
      endosulfan, and heptachlor), and air pollution. The next group identified were
      neurotoxicants exhibiting gender-specific neurotoxic effects, with males being
      somewhat (but not consistently) more affected than females: mercury vapor,
      polychlorinated biphenyls (PCBs), and organophosphate pesticides. Finally, there
      was a group of studies in which the neurotoxicants exhibited apparent gender
      related neurotoxic effects but failed to show whether exposed males were
      consistently more affected than females: inorganic mercury salts, methylmercury
      species, and certain endocrine disruptors (e.g., phthalates and BPA). The overall
      conclusion from the studies reviewed was that the brain in males is more
      vulnerable to many toxic exposures than it is in females. Evidence suggests that
      the reasons for the male brain being more vulnerable include: (1) greater
      glutathione availability in females; (2) greater sulfate-based detoxification
      capacity in females; (3) potentiating effects of co-exposure to neurotoxicants
      and testosterone; (4) greater neuroinflammatory response in males; (5) reduced
      vulnerability to oxidative stress in females; and (6) neuroprotective effects of
      female hormones (estrogen and progesterone), especially in the reduction of
      inflammation and oxidative stress.

PMID- 29369295
TI  - Omitted Stimulus Potential Depends on the Sensory Modality.
AB  - Determining the characteristics of Omitted Stimulus Potential (OSP) parameters
      using different sensory modalities is important because they reflect timing
      processes and have a substantial influence on time perception. At the same time,
      the central mechanisms of time perception associated with sensory processing can
      modulate cortical brain waves related to cognition. This experiment tested the
      relationship between parameters of the whole OSP brain wave when trains of
      auditory, visual or somatosensory stimuli were applied. Twenty healthy young
      college volunteers completed within-subjects trials with sensory stimuli at a
      fixed frequency of 0.5 Hz that ceased unpredictably. These passive trials
      required no behavioural response and were administered to measure the complete
      set of OSP (i.e., the rate of rise, amplitude and peak latency). OSPs showed a
      faster rate of rise for auditory stimuli compared to visual or somatosensory
      stimuli. Auditory stimuli also produced a shorter time to peak and higher
      amplitude waves. No significant differences were obtained between visual and
      somatosensory waves. The results suggest that the brain handles interval timing
      and expectation with greater efficiency for the auditory system compared to other
      sensory modalities. This auditory supremacy is congruent with previous
      behavioural studies using missing stimulus tasks and could be useful for clinical
      purposes, for example, designing auditory-based brain-computer interfaces for
      patients with motor disabilities and visual impairment. The rate of rise is a
      dynamic measure that should be included in the ERPs analysis.

PMID- 29369296
TI  - Top-down and bottom-up competition in visual stimuli processing.
AB  - Limited attention capacity results that not all the stimuli present in the visual
      field are equally processed. While processing of salient stimuli is automatically
      boosted by bottom-up attention, processing of task-relevant stimuli can be
      boosted volitionally by top-down attention. Usually, both top-down and bottom-up
      influences are present simultaneously, which creates a competition between these
      two types of attention. We examined this competition using both behavioral and
      electrophysiological measures. Participants responded to letters superimposed on
      background pictures. We assumed that responding to different conditions of the
      letter task engages top-down attention to different extent, whereas processing of
      background pictures of varying salience engages bottom-up attention to different
      extent. To check how manipulation of top-down attention influences bottom-up
      processing, we measured evoked response potentials (ERPs) in response to pictures
      (engaging mostly bottom-up attention) during three conditions of a letter task
      (different levels of top-down engagement). Conversely, to check how manipulation
      of bottom-up attention influences top-down processing, we measured ERP responses
      for letters (engaging mostly top-down attention) while manipulating the salience
      of background pictures (different levels of bottom-up engagement). The
      correctness and reaction times in response to letters were also analyzed. As
      expected, most of the ERPs and behavioral measures revealed a trade-off between
      both types of processing: a decrease of bottom-up processing was associated with
      an increase of top-down processing and, similarly, a decrease of top-down
      processing was associated with an increase in bottom-up processing. Results
      proved competition between the two types of attentions.

PMID- 29369297
TI  - Antiallodynic effect of intrathecal resiniferatoxin on neuropathic pain model of
      chronic constriction injury.
AB  - INTRODUCTION: Injuries and/or dysfunctions in the somatosensory system can lead
      to neuropathic pain. Transient receptor potential vanilloid sub-type 1 (TRPV1)
      play an important role in the development of allodynia and hyperalgesia following
      injury and the ensuing inflammatory conditions. Resiniferatoxin (RTX) is an
      ultrapotent synthetic TRPV1 agonist and many different administration routes are
      available for different mechanisms and different effects. RTX is used
      intraperitonially as a model of neuropathic pain or epidurally and topically to
      produce prolonged analgesic effects. However, the use of RTX is controversial
      because its neurotoxicity and margin of safety have not been addressed
      adequately. The present study evaluates the effect of intrathecal RTX on the
      induction and allodynia behavior of animals submitted to neuropathic pain by
      chronic constriction injury (CCI). METHODS: 160 Swiss mice were randomly
      distributed into two groups: intrathecal pre-treatment group (PRE) aiming the
      effect in induction of allodynia and late intrathecal treatment group (POST) to
      evaluate the antiallodynic effect of the RTX on mechanical nociceptive threshold
      evaluated by the Von Frey hair filaments. Additionally, we evaluated the
      expression of TRPV1 in dorsal root ganglia (DRG) by western blotting after PRE-
      and POST-treatment with RTX. RESULTS: Our results showed that the CCI mice
      developed prolonged mechanical allodynia-like behavior in ipsilateral paw after
      surgery up to 24 hours. The PRE- and POST-treatment groups presented significant
      antiallodynic effects in ipsilateral paw for 24 hours. Only the POST-treatment
      group showed a significant reduction of expression of the TRPV1 receptor after
      CCI. CONCLUSION: The presented data demonstrated that both PRE- and POST
      treatment with RTX given intrathecally produced potent antiallodynic activities
      in CCI mice and that POST-treatment can reduce TRPV1 expression in DRG,
      suggesting that POST-treatment RTX can revert central sensitization and its
      associated allodynia.

PMID- 29369298
TI  - Effects of different delayed exercise regimens on cognitive performance in
      fimbria-fornix transected rats.
AB  - Studies have shown that exercise can positively influence cognitive performance
      after brain injury. This study investigated the effects of different exercise
      regimens on allocentric place learning after fimbria-fornix (FF) transection. One
      hundred and sixteen pre-shaped rats were subjected either to a mechanical
      transection of the FF or control sham surgery and divided into following groups:
      i) no exercise (NE), ii) voluntary exercise in a running wheel (RW), iii) forced
      swimming exercise administered as interval training of short (3x5 min) duration
      (FS-SI), iv) forced swimming exercise administered as interval training of long
      (3x15 min) duration (FS-LI), v) forced swimming exercise administered as one
      session of short (5 min) duration (FS-SS), and vi) forced swimming exercise
      administered as one session of long (15 min) duration (FS-LS). The exercise was
      initiated 21 days post-surgery. Subsequently, all animals were administered 28
      acquisition sessions in an 8-arm radial maze. Both sham operated and lesioned
      animals showed a significant learning response, however, the lesion induced a
      marked and lasting impairment, which was not alleviated neither by voluntary nor
      forced (spaced or one-session only) exercise regimens. Exercise regimens had no
      effect on the place learning of control sham animals. We conclude that the lesion
      location as well as factors related to the exercise- and cognitive testing
      protocols can profoundly influence the potential of exercise as a general
      recovery-promoting method.

PMID- 29369299
TI  - Axonal outgrowth stimulation after alginate/mesenchymal stem cell therapy in
      injured rat spinal cord.
AB  - Despite strong efforts in the field, spinal cord trauma still belongs among the
      untreatable neurological conditions at present. Given the complexity of the
      nervous system, an effective therapy leading to complete recovery has still not
      been found. One of the potential tools for supporting tissue regeneration may be
      found in mesenchymal stem cells, which possess anti-inflammatory and trophic
      factor-producing properties. In the context of transplantations, application of
      degradable biomaterials which could form a supportive environment and scaffold to
      bridge the lesion area represents another attractive strategy. In the present
      study, through a combination of these two approaches we applied both alginate
      hydrogel biomaterial alone or allogenic transplants of MSCs isolated from bone
      marrow seeded in alginate biomaterial into injured rat spinal cord at three weeks
      after spinal cord compression performed at Th8-9 level. Following three-week
      survival, using immunohistochemistry we studied axonal growth (GAP-43 expression)
      and both microglia (Iba-1) and astrocyte (GFAP) reactions at the lesion site and
      in the segments below and above the lesion. To detect functional improvement,
      during whole survival period we performed behavioral analyses of locomotor
      abilities using a classical open field test (BBB score) and a Catwalk automated
      gait analyzing device (Noldus). We found that despite the absence of locomotor
      improvement, application of both alginate and MSCs caused significant increase in
      the number of GAP-43 positive axons.

PMID- 29369300
TI  - Interaction between the serotoninergic and GABAergic systems in frog retina as
      revealed by electroretinogram.
AB  - Functional interactions between serotoninergic and GABAergic systems in the
      vertebrate retina are largely unknown. In this study, the effects of isolated or
      combined stimulation of the serotonin receptors (with 100 MUM serotonin) and
      ionotropic GABAA and GABAC receptors (with 5 mM TACA) on the electroretinographic
      (ERG) ON (b-wave) and OFF (d-wave) responses were investigated in frog eyecup
      preparations. It was found that serotonin alone produced a significant
      enhancement of the b- and d-wave amplitude, while TACA alone caused its marked
      diminution. The relative amplitude diminution, caused by the TACA treatment, was
      significantly smaller when TACA was applied on the background of the fully
      developed serotonin effect. This result suggests that the retinal serotoninergic
      system could diminish the effects of ionotropic GABA receptor activation on the
      ERG wave generator mechanisms. In order to separately evaluate the effects of the
      GABAC receptor activation, in a subset of experiments the effects of TACA or TACA
      + serotonin were tested during GABAA receptor blockade with 100 MUM bicuculline.
      Bicuculline alone caused a marked increase of the b- and d-wave amplitude. The
      stimulation of GABAC receptors (with TACA) during bicuculline action produced a
      strong diminution of the b- and d-wave amplitudes. Similar relative decrease of
      the b-wave amplitude was produced when TACA was applied in combination with
      serotonin, while the relative decrease of the d-wave amplitude was less
      pronounced during treatment with serotonin + TACA than TACA alone. Our results
      demonstrate that there is an ON/OFF asymmetry in the receptors involved in the
      presumed interactions between serotoninergic and GABAergic systems. Serotonin may
      decrease the effects of GABAA receptor activation in the ON pathway, while it may
      decrease the effects of both GABAA and GABAC receptor activation in the OFF
      pathway.

PMID- 29369301
TI  - Effects of ascorbic acid on anxiety state and affect in a non-clinical sample.
AB  - : Objective Given that the literature data indicates that ascorbic acid may have
      an anxiolytic effect, we hypothesized that a single oral administration of
      ascorbic acid could acutely affect emotional states. Methods The effects of acid
      ascorbic supplementation on anxiety and other emotional states were evaluated by
      the State-Trait Anxiety Inventory (STAI), and Visual Analogue Mood Scale (VAMS).
      Immediately before, and 2 hours after receiving a single ascorbic acid dose (1000
      mg) or placebo, 142 graduate students were evaluated by the STAI and VAMS in a
      randomized, double-blind, placebo-controlled trial. Results No changes from basal
      levels were observed in the STAI state-anxiety or VAMS scores. However, the
      ingestion of ascorbic acid by the 25% more anxious healthy subjects (women; 14
      control and 23 ascorbic acid), as defined by the STAI trait-anxiety scale,
      produced a significant reduction from baseline anxiety scores in the STAI state
      anxiety scale and VAMS anxiety subscale. The study evaluated a small sample with
      narrow sociodemographic characteristics, composed mainly of healthy young females
      (> 94%) enrolled in post-graduation courses, without controlling diet, physical
      activity, and formal psychiatric diagnosis. CONCLUSIONS: Despite the sample size
      limitation, this study provides the first evidence of an acute anxiolytic effect
      of ascorbic acid. Broader population studies are required to evaluate the
      clinical relevance of presented data.

PMID- 29369302
TI  - Antimuscarinic-induced convulsions in fasted mice after food intake: No evidence
      of spontaneous seizures, behavioral changes or neuronal damage.
AB  - Prolonged or repeated seizures have been shown to cause spontaneous recurrent
      seizures, increased anxiety-related behavior, locomotor hyperactivity, impaired
      functions of learning and memory, and neuronal damage in the hippocampus and
      other brain regions in animals. Mice and rats treated with antimuscarinic drugs
      after fasting for two days or less develop convulsions after being allowed to eat
      ad libitum. To address whether such behavioral and neuroanatomic changes occur
      following these convulsions, mice treated i.p. with saline (control) or 2.4 mg/kg
      atropine and given food after 24 h of fasting were grouped according to seizure
      scores for behavioral and histological analysis. Following convulsions, the
      occurrence of spontaneous recurrent seizures was observed for 30 days. Motor
      activity and grooming behavior were assessed in the open field, and memory was
      assessed using the novel object recognition test 4 and 7 days after onset of
      convulsions, respectively. Animals allocated for the histological analysis were
      decapitated 7 days after onset of convulsions and hippocampal slices were
      evaluated for the percentage of degenerating neurons stained with Fluoro-Jade C.
      Spontaneous recurrent seizures, locomotor alterations, anxiety-related behavior,
      memory impairment, and neuronal loss in the granular layer of the dentate gyrus
      were not detected in the animals with seizure score 1-2 or 3-5. These results are
      in accordance with those related to the absence of behavioral changes, cognitive
      deficits, and hippocampal neuronal damage after single brief seizures in animals
      and patients with epilepsy.

PMID- 29369303
TI  - Report from the International Conference on Viral Hepatitis - 2017.
AB  - The International Conference on Viral Hepatitis 2017 brought exciting news on the
      treatment of viral hepatitis. The most recent estimates of the burden for
      hepatitis B virus and hepatitis C virus (HCV) infections were presented. The
      current gaps and prospects for regional and global eradication of viral hepatitis
      were discussed on the light of the WHO roadmap until 2030. Debates focused on
      hepatitis C and expectations using the new approved HCV pan-genotypic, once
      daily, oral direct-acting antivirals (DAAs), glecaprevir-pibrentasvir, and
      sofosbuvir-velpatasvir-voxilaprevir. The management of difficult-to-cure HCV
      patients included individuals who had failed prior DAAs, people who inject drugs,
      patients with decompensated cirrhosis, or renal insufficiency. Special patient
      populations such as children, pregnant women, persons with acute hepatitis C, or
      HIV coinfection were addressed separately. The use of HCV treatment as prevention
      was subject to debate, balancing the benefits on halting transmission and the
      risk for HCV reinfections and high medication costs. Complementary efforts on
      behavioral interventions and harm reduction programs were highlighted. Data from
      both clinical trials and real-world experience (i.e., from the US Veterans) were
      compared. Further debates addressed hepatic conditions that may alter the
      management and outcome of viral hepatitis, such as hepatitis B reactivation, non
      alcoholic fatty liver disease, liver transplantation, and hepatocellular
      carcinoma. Finally, the recent data on often neglected hepatitis D and E virus
      infections were reviewed.

PMID- 29369304
TI  - Antiretroviral Therapy in Advanced HIV Disease: Which is the Best Regimen?
AB  - Advanced HIV disease, defined as a CD4 cell count below 200 cells/MUl or the
      presence of an AIDS-defining illness, remains common among HIV-infected
      individuals who first present for medical care. In developed countries, nearly
      30% of new HIV diagnoses occurred at advanced stages of the disease, and it is
      important because advanced HIV disease has been associated with worse clinical
      outcomes, including lower rates of virological response, higher morbidity, and
      higher mortality. However, there are scarce data regarding which is the best
      antiretroviral regimen in these patients. Nowadays, integrase inhibitor-based
      regimens are widely recommended as the best initial therapy for treatment-naive
      HIV-infected patients by all international guidelines. However, these guidelines
      hardly mention the recommended regimens in individuals with advanced HIV disease.
      Otherwise, recent data indicating a higher risk of immune reconstitution
      inflammatory syndrome associated to the use of integrase inhibitors have raised
      concerns on the use of these drugs in patients with advanced HIV disease. The aim
      of this article is to review the available evidence from randomized clinical
      trials for the best treatment in patients with advanced HIV disease.

PMID- 29369305
TI  - Nucleostemin regulates proliferation and migration of gastric cancer and
      correlates with its malignancy [Retraction].
AB  - [This retracts the article on p. 17634 in vol. 8, PMID: 26770353.].

PMID- 29369306
TI  - A comparison study of immune-inflammatory response in electroacupuncture and
      transcutaneous electrical nerve stimulation for patients undergoing
      supratentorial craniotomy [Retraction].
AB  - [This retracts the article on p. 2662 in vol. 8, PMID: 25932216.].

PMID- 29369307
TI  - Formal recognition of the species of Oreosaurus (Reptilia, Squamata,
      Gymnophthalmidae) from the Sierra Nevada de Santa Marta, Colombia.
AB  - Oreosaurus is one of the two genera extracted from the former Riamasensu lato,
      which was recently recognized as polyphyletic. Oreosaurus is a small clade (five
      named and two undescribed species) of montane gymnophthalmid lizards and exhibits
      an exceptional distributional pattern. Its nominal and undescribed species are
      discontinuously distributed on the Cordillera de la Costa of Venezuela, the
      tepuis from the Chimanta massif in Venezuela, the highlands of the island of
      Trinidad, and the Sierra Nevada de Santa Marta in Colombia (SNSM). Herein, we
      describe the species of Oreosaurus that is endemic to the SNSM. Historically,
      this species associates with two names that are currently nomina nuda:
      Proctoporus serranus and P. specularis. Formal nomenclatural recognition of
      Oreosaurus serranussp. n. renders specularis a permanently unavailable name for
      this taxon. Oreosaurus serranussp. n. is the sister of all remaining congeners,
      and differs primarily from them in having only one pair of genial scales, as well
      as a unique pattern of scutellation. We provide an identification key to the
      species of Oreosaurus.

PMID- 29369308
TI  - Photo-triggered micelles: simultaneous activation and release of microtubule
      inhibitors for on-demand chemotherapy.
AB  - The nonspecific biodistribution of cytotoxic drugs and associated adverse effects
      greatly limit the efficacy and patient compliance of chemotherapy. To address
      this, we employed a photoswitchable microtubule inhibitor (Azo-CA4) that was
      physically loaded in cyclodextrin-bearing micellar nanocarriers through the host
      guest interaction. Azo-CA4 was only activated upon ultraviolet (UV) light
      irradiation to trigger the transition from the "trans" (inactive) to "cis"
      (active) state. Such conformation change could then induce rapid Azo-CA4 release
      from micelles without the delay of the onset of therapeutic action. This
      nanoscale delivery system produced photo-triggered antimitotic and pro-apoptotic
      effects in MDA-MB-231 cells via a triggered control of microtubule dynamics. The
      anticancer efficacy of Azo-CA4-loaded micelles was further proved in vivo using a
      4T1 tumor-bearing mice model coupled with multiple topical administrations to
      avoid the penetration problem of UV light. This work provides a new delivery
      vehicle to aid the application and potential translation of Azo-CA4 as biomedical
      tools and precision chemotherapeutics.

PMID- 29369309
TI  - Enhanced bone defect repairing effects in glucocorticoid-induced osteonecrosis of
      the femoral head using a porous nano-lithium-hydroxyapatite/gelatin
      microsphere/erythropoietin composite scaffold.
AB  - Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a common
      debilitating disease that occurs in young and middle-aged adults. To treat early
      GIONFH, core decompression and bone graft are regarded as effective measures.
      However, the ideal bone graft should possess bioactivity as well as biomechanical
      properties. The most commonly used bone graft materials are currently
      unsatisfactory. In this study, we fabricated a composited scaffold using lithium
      (Li) to activate the Wnt signal pathway and erythrogenin (EPO) to upregulate the
      HIF-1/VEGF pathway to improve the osteogenic and angiogenic effects of the
      scaffold. We obtained the porous gelatin/nano-lithium-hydroxyapatite/gelatin
      microsphere/rhEPO (Li-nHA/GMs/rhEPO) composited scaffold and assessed its
      mechanical properties, release properties, and in vitro bioactivity. Then, we
      implanted the scaffold into the femoral heads of GIONFH rabbits after core
      decompression surgery and evaluated the osteogenic and angiogenic abilities of
      the scaffold in vivo as well as its bone defect repair efficacy. As the results
      show, the Li-nHA/GM/rhEPO scaffold possessed good mechanical compression strength
      and enabled continuous release of Li and rhEPO. Moreover, the scaffold improved
      the viability of glucocorticoid-treated BMMSCs and vascular endothelial cells and
      increased the expression of osteogenic and angiogenic factors. In the in vivo
      study, the composited scaffold improved new bone formation and exerted effects on
      repairing femoral head defects in GIONFH rabbits. Additionally, the osteogenic
      and angiogenic factors were increased along with the activation of factors in the
      Wnt signal pathway and the HIF-1/VEGF pathway. In conclusion, the Li-nHA/GM/rhEPO
      scaffold can upregulate the Wnt and HIF-1/VEGF pathways at same time and has
      effects on improving osteogenesis and angiogenesis, which benefits the repair of
      GIONFH.

PMID- 29369310
TI  - A peptide-based synthetic transcription factor selectively activates
      transcription in a mammalian cell.
AB  - A peptide-based cell permeable synthetic transcription factor is reported, which
      binds to its target site with high affinity and specificity. When linked to a HAT
      binding peptide, it causes significant upregulation of gene expression in a
      mammalian cell. Such molecules may be developed for selectively activating
      repressed genes in mammalian cells.

PMID- 29369311
TI  - The Janus-faced chromophore: a donor-acceptor dyad with dual performance in
      photon up-conversion.
AB  - An electron donor-acceptor dyad based on BODIPY (acceptor) and anthracene (donor)
      plays either the role of sensitizer or emitter in triplet-triplet annihilation
      photon up-conversion (TTA-UC). This Janus-like behavior was achieved via altering
      the relative ordering of charge-transfer and local excited state energies in the
      dyad through the polarity of TTA-UC media.

PMID- 29369312
TI  - Direct thermal desorption gas chromatographic determination of toxicologically
      relevant concentrations of ethylene glycol in whole blood.
AB  - A simple and rapid method involving thermal desorption gas chromatography (TD-GC)
      with flame ionisation detection has been successfully developed for the
      determination of ethylene glycol in whole blood. No sample extraction or
      derivatization steps were required. The conditions required for the direct
      determination of ethylene glycol in whole blood were optimised and require only
      the addition of the internal standard, 1,2-butanediol, to the sample. A 1 MUL
      aliquot of the sample was then introduced to the thermal desorption unit, dried,
      and thermally desorbed directly to the gas chromatograph. A calibration curve was
      constructed over the concentration range of 1.0 to 200 mM and was found to be
      linear over the range investigated with an R2 value of 0.9997. The theoretical
      limit of detection based on 3sigma was calculated to be 50.2 MUM (3.11 mg L-1).
      No issues with carryover were recorded. No interferences were recorded from
      endogenous blood components or a number of commonly occurring alcohols. The
      proposed method was evaluated by carrying out replicate ethylene glycol
      determinations on fortified whole blood samples at the levels of 12.5 mM, 20.0
      mM, 31.2 mM, 100 mM and 200 mM comparable to commonly reported blood levels in
      intoxications. Mean recoveries of between 84.8% and 107% were obtained with
      coefficients of variation of between 1.7% and 5.8%. These data suggest that the
      method holds promise for applications in toxicology, where a rapid, reliable
      method to confirm ethylene glycol poisoning is required.

PMID- 29369313
TI  - Through bond and through space interactions in dehydro-diazine radicals: a case
      study of 3c-5e interactions.
AB  - Owing to the 3c-5e (3-centred-5-electrons) interactions between two nitrogen lone
      pairs and a radical electron, the dehydrodiazine radical isomers are very
      interesting from the fundamental point of view. Among them, pyrimidine has three
      (1a-1c), pyridazine has two (2a and 2b) and pyrazine has only one (3a) radical
      isomer. Based on quantum chemical calculations at the (U)B3LYP, (U)M06-2X,
      (U)BLYP, CBS-QB3 and (U)CCSD(T) levels with cc-pVTZ as the basis set, we found
      the 4-dehydropyrimidine (1b) radical to be the most stable isomer among the three
      pyrimidine radicals, followed by the 2-dehydropyrimidine (1a) and 5
      dehydropyrimidine (1c) radical isomers. In the case of pyridazine, 3-dehydro
      radical isomer (2a) is more stable than 4-dehydropyridazine (2b). Bond
      dissociation energy (BDE) calculations and estimation of radical stabilization
      energies (RSE) using isodesmic reactions revealed the stability order among the
      six isomeric diazine radicals as 1c < 2b < 2a < 1a < 3a < 1b. Spin densities at
      each radical centre and non-zero values at nitrogen centres provided information
      about the extent of delocalization of radical electrons, which was consistent
      with the relative stability order of all the isomers. The multiconfigurational
      CASSCF and natural bond orbital (NBO) calculations suggested the presence of
      direct through space interactions (between lone pairs and a radical, TS) that
      play a dominant role over the through bond (through intervening bonds, TB)
      interactions in deciding the stability order. To confirm these results, we have
      also estimated the proton affinities (PAs) for each nitrogen atom and compared
      them with their respective parent diazines, where lowering of the PA values
      convincingly envisaged the extent and strength of interactions between the
      nitrogen and radical centre. Atoms-in-molecules (AIM) analysis and estimation of
      hyperfine coupling constants have also been performed to verify these results.
      All these results showed that the through space interaction between the lone pair
      and the radical electron is very important for the electronic structural and
      stability aspects in dehydrodiazine radicals.

PMID- 29369314
TI  - Synthesis, functionalization, and applications of metal-organic frameworks in
      biomedicine.
AB  - Metal-organic frameworks (MOFs), also known as coordination polymers, have
      attracted extensive research interest in the past few decades due to their unique
      physical structures and potentially vast applications. In this review, we outline
      the recent progress in the synthesis, functionalization and applications of MOFs
      in biomedicine, mainly focusing on two promising, yet challenging areas, i.e.,
      drug delivery and biosensing applications. A major challenge is the proper
      functionalization of MOFs with demanding properties suitable for biomedical
      applications. Extensive studies on MOFs in biomedicine have led to substantial
      progress in the control of key properties of MOFs such as toxicity, size and
      shape, and biological stability. Due to their flexible composition, pore size and
      easy functionalization properties, MOFs can be utilized as key components for the
      development of various functional systems, and their applications in drug
      delivery and biosensing are reviewed. Future trends and perspectives in these
      research areas are also outlined.

PMID- 29369315
TI  - Band gap modification and photoluminescence enhancement of graphene nanoribbon
      filled single-walled carbon nanotubes.
AB  - Molecule encapsulation inside the single-walled carbon nanotube (SWCNT) core has
      been demonstrated to be a successful route for the modification of nanotube
      properties. SWCNT diameter-dependent filling results in band gap modification
      together with the enhancement of photoluminescence quantum yield. However, the
      interaction between the inner structure and the outer shell is complex. It
      depends on the orientation of the molecules inside, the geometry of the host
      nanotube and on several other mechanisms determining the resulting properties of
      the hybrid nanosystem. In this work we study the influence of encapsulated
      graphene nanoribbons on the optical properties of the host single-walled carbon
      nanotubes. The interplay of strain and dielectric screening caused by the
      internal environment of the nanotube affects its band gap. The photoluminescence
      of the filled nanotubes becomes enhanced when the graphene nanoribbons are
      polymerized inside the SWCNTs at low temperatures. We show a gradual
      photoluminescence quenching together with a selective signal enhancement for
      exact nanotube geometries, specifically (14,6) and (13,8) species. A precise
      adjustment of the optical properties and an enhancement of the photoluminescence
      quantum yield upon filling for nanotubes with specific diameters were assigned to
      optimal organization of the inner structures.

PMID- 29369316
TI  - Photoactivated proton coupled electron transfer in DNA: insights from quantum
      mechanical calculations.
AB  - The energetics of the two main proton coupled electron transfer processes that
      could occur in DNA are determined by means of time dependent-DFT calculations,
      using the M052X functional and the polarizable continuum model to include solvent
      effect. This approach has been applied to fragments of GC and AT alternated
      duplexes containing up to 4 base pairs. In GC DNA, intra-strand G -> C charge
      transfer (CT) can trigger inter-strand Proton Transfer (PT) involving the C
      anion, since the reaction is exothermic and the related energy barrier is <0.3
      eV. In AT DNA, the minimum resulting from intra-strand A -> T CT is not predicted
      to undergo inter-strand PT. These conclusions are in full agreement with the
      indication of time-resolved IR spectra. In both systems, inter-strand CT can be
      coupled to inter-strand PT, and the resulting minimum, reached after overcoming a
      moderate energy barrier (<0.4 eV), is close to a crossing region with the ground
      electronic state, providing a relatively fast non-radiative deactivation route.

PMID- 29369317
TI  - Diacylhydrazone-assembled {Ln11} nanoclusters featuring a "double-boats
      conformation" topology: synthesis, structures and magnetism.
AB  - A family of novel Ln nanoclusters, namely, [Ln11(ovpho)4(MU-CH3O)2(MU-H2O)2(MU3
      OH)6(CH3OH)4(H2O)2(NO3)8](OH).xH2O.yCH3OH [Ln = Gd (1), x = 1, y = 3; Ln = Tb
      (2), x = 1, y = 3; Ln = Dy (3), x = 0, y = 3], was obtained via solvothermal
      reactions of Ln(NO3)3 with a diacylhydrazone ligand N,N'-bis(o
      vanillidene)pyridine-2,6-dicarbohydrazide N-oxide (H4ovpho). Their isostructural
      molecular structures are composed of two crystallographically symmetric {Ln6}
      rings sharing a Ln3+ ion, and display an unprecedented "double boat conformation"
      topology that, to our knowledge, has not yet been reported. Ophenol, Oenol and
      Ooxynitride from ovpho4- ligands, as well as Omethanol, Owater and Ohydroxyl help
      to bridge the Ln3+ ions. The structural variation between these {Ln11} clusters
      and a previously reported {Gd18} nanowheel, both of which are assembled by
      H4ovpho under the same synthetic method and reaction conditions, is caused only
      by changing the anions of Ln salts. Magnetic investigations revealed a large
      magnetocaloric effect (MCE) of 1, whose maximum -DeltaSm value reaches 30.1 J kg
      1 K-1 for DeltaH = 50 kOe at 2.0 K. Additionally, it was found that 3 shows
      single-molecule magnets (SMMs) behavior, with an approximated energy barrier Ueff
      = 6.13 K and pre-exponential factor tau0 = 1.70 * 10-6 s.

PMID- 29369318
TI  - In situ probing behaviors of single LiNiO2 nanoparticles by merging CAFM and AM
      FM techniques.
AB  - Probing single active nanoparticles of Li-ion battery electrodes is challenging
      but important to reveal their behaviors including morphology, mechanical
      properties and electrochemical reactions with an electrolyte. In this work, we in
      situ investigated voltage-induced behaviors of single LiNiO2 nanoparticles by
      merging conductive atomic force microscopy (CAFM) and amplitude modulation
      frequency modulation (AM-FM) techniques. The former was used to apply a voltage
      between a selected single nanoparticle and a substrate through its tip, while the
      latter was done for imaging. Evolution in the morphology and stiffness of the
      nanoparticles induced by different voltages under air and dried argon atmospheres
      was tracked, respectively. The evolution mechanisms related to electrochemical
      reactions were discussed in detail. These results suggest that the merged
      techniques would provide an indirect and effective approach to study the
      behaviors and electrochemical reactions of electrode materials on the nanometer
      scale and even single nanoparticles.

PMID- 29369319
TI  - Endogenous sialic acid-engineered micelles: a multifunctional platform for on
      demand methotrexate delivery and bone repair of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) patients have suffered from the current drug
      therapeutic regimen because of its high toxicity and the absence of bone
      regeneration for existing erosion, seriously affecting the quality of life.
      Herein, a sialic acid-dextran-octadecanoic acid (SA-Dex-OA) conjugate was
      synthesized to form micelles with a 55.06 MUg mL-1 critical micelle
      concentration. The obtained micelles can encapsulate a disease-modifying anti
      rheumatic drug, methotrexate (MTX), with 4.28% (w/w) drug content, featuring
      sustained drug release behavior over 48 h. In vitro and in vivo studies showed
      that SA-Dex-OA micelles significantly improved accumulation and transportation
      through a combination of SA and E-selectin receptors in inflamed cells and
      arthritic paws highly expressing E-selectin. MTX-loaded SA-Dex-OA micelles not
      only significantly inhibited the inflammatory response, but also diminished the
      adverse effects of MTX, as reflected by the reduced alanine aminotransferase,
      aspartate aminotransferase, creatinine, and urea nitrogen levels. Most
      importantly, the bone mineral density in rats treated with MTX-loaded SA-Dex-OA
      micelles was significantly higher as compared to in those treated with free MTX
      and Dex-OA/MTX micelles (increasing from 391.4 to 417.4 to 492.7 mg cc-1),
      benefiting from the effects of endogenous sialic acid in promoting MC3T3-E1 cell
      differentiation and mineralization. It is anticipated that SA-based micelles with
      bone repair activities have great potential for RA treatment and other metabolic
      bone diseases with serious bone erosion.

PMID- 29369320
TI  - Efficient construction of bioactive trans-5A5B6C spirolactones via bicyclo[4.3.0]
      alpha-hydroxy ketones.
AB  - An efficient, convenient short synthetic procedure for the synthesis of the
      intricate 5A5B6C-ring fusion topologies of tricyclic spiranoid beta
      hydroxybutyrolactones through lactonization of the key intermediate trans-alpha
      hydroxyindenones with malonates is described. All the compounds synthesized
      exhibited environmentally benign characteristics, moderate fungicidal,
      nematocidal, and anti-TMV activities.

PMID- 29369331
TI  - Alterations in local stability and dynamics of A4V SOD1 in the presence of
      trifluoroethanol.
AB  - Alterations in the local dynamics of Cu/Zn Superoxide dismutase (SOD1) due to
      mutations affect the protein folding, stability, and function leading to
      misfolding and aggregation seen in amyotrophic lateral sclerosis (ALS). Here, we
      study the structure and dynamics of the most devastating ALS mutation, A4V SOD1
      in aqueous trifluoroethanol (TFE) through experiments and simulation. Far-UV
      circular dichroism (CD) studies shows that TFE at intermediate concentrations
      (~15% - 30%) induce partially unfolded beta-sheet-rich extended conformations in
      A4V SOD1 which subsequently aggregates. Molecular dynamics (MD) simulation
      results shows that A4V SOD1 increases local dynamics in the active site loops
      that leads to the destabilization of the beta-barrel and loss of hydrophobic
      contacts, thus stipulating a basis for aggregation. Free energy landscape (FEL)
      and essential dynamics (ED) analysis demonstrates the conformational
      heterogeneity in A4V SOD1. Our results thus shed light on the role of local
      unfolding and conformational dynamics in aggregation of SOD1.

PMID- 29369332
TI  - Morphometric panel regression equations for predicting body mass in immature
      humans.
AB  - OBJECTIVES: Predicting body mass is a frequent objective of several
      anthropological subdisciplines, but there are few published methods for
      predicting body mass in immature humans. Because most reference samples are
      composed of adults, predicting body mass outside the range of adults requires
      extrapolation, which may reduce the accuracy of predictions. Prediction equations
      developed from a sample of immature humans would reduce extrapolation for
      application to small-bodied target individuals, and should have utility in
      multiple predictive contexts. MATERIALS AND METHODS: Here, we present two novel
      body mass prediction equations derived from 3468 observations of stature and bi
      iliac breadth from a large sample of immature humans (n = 173) collected in the
      Harpenden Growth Study. Prediction equations were generated using raw and natural
      log-transformed data and modeled using panel regression, which accounts for
      serial autocorrelation of longitudinal observations. Predictive accuracy was
      gauged with a global sample of human juveniles (n = 530 age- and sex-specific
      annual means) and compared to the performance of the adult morphometric
      prediction equation previously identified as most accurate for human juveniles.
      RESULTS: While the raw data panel equation is only slightly more accurate than
      the adult equation, the logged data panel equation generates very accurate body
      mass predictions across both sexes and all age classes of the test sample (mean
      absolute percentage prediction error = 2.47). DISCUSSION: The logged data panel
      equation should prove useful in archaeological, forensic, and paleontological
      contexts when predictor variables can be measured with confidence and are outside
      the range of modern adult humans.

PMID- 29369333
TI  - Confocal microscopy in adult women with acne.
AB  - BACKGROUND: Acne is an inflammatory disease of the pilosebaceous follicle,
      affecting 41-54% of adult women, with a particular form that involves the
      mandible. METHODS: We characterized infundibulum morphology in two groups of
      adult women using reflectance confocal microscopy. First, we investigated acne
      visually "healthy zones" on the forehead in 15 adult women with diffuse acne and
      compared with acne-free controls. We then compared healthy forehead and affected
      mandibular zone in 15 acne patients with mandibular involvement. Exposed results
      had a P < 0.05. RESULTS: Seven hundred and ninety-one follicles were observed on
      apparently healthy skin of 15 adult women with acne, with a larger diameter,
      thicker (68%), and hyper keratinized (65%) follicle border, and more keratin
      plugs (44%) than in controls. In the second group of 15 adult women with
      mandibular acne, we compared 569 follicles in the mandibular zone and 475 on
      forehead. In the mandibular area, follicles were significantly larger, thicker
      (76%), more hyper keratinized (72%), with more keratin plugs (47%) and increased
      inflammation (23%) compared with the forehead area. In the mandibular area, 0.2%
      of follicles showed isolated inflammation without hyper keratinization, and 15.3%
      had both thickened borders with an onion-like appearance and keratin plugs
      associated with inflammation. CONCLUSIONS: Hyper keratinization was higher in
      healthy skin of adult women with acne compared with controls, confirming that
      microcomedo is crucial in the development of acne lesions. We also demonstrate
      that the repartition of comedones and microcomedones is inhomogeneous with a
      great number in the mandibular area where acne lesions are located.

PMID- 29369334
TI  - The incidental thyroid nodule.
AB  - Incidental thyroid nodules that are found on an imaging study performed for
      reasons other than thyroid pathology represent a common scenario encountered by
      health care providers. The initial workup for these nodules comprises a thorough
      history and physical examination, thyroid function tests, a dedicated thyroid
      ultrasound, and fine-needle aspiration of any suspicious lesions. Management
      ranges from observation and reassurance to surgical resection and depends on the
      cytologic diagnosis. In cases of cytologically indeterminate or discordant
      nodules, surgical excision (lobectomy) offers a definitive diagnosis, although
      molecular testing or a reasonable period of observation may be useful as less
      invasive adjuncts. CA Cancer J Clin 2018;68:97-105. (c) 2018 American Cancer
      Society.

PMID- 29369335
TI  - The effect of music therapy on infants born preterm.

PMID- 29369336
TI  - Economic consequences of over-diagnosis of threatened preterm labor.
AB  - OBJECTIVE: To investigate whether adherence to a cervical length-based protocol
      can reduce both unnecessary admissions and the socioeconomic costs associated
      with inappropriately admitted patients. METHODS: The present retrospective
      observational study included women admitted for threatened preterm labor (TPL) at
      24-34 weeks of pregnancy to a tertiary hospital in the Canary Islands, 2009-2014.
      Data were reviewed from all patients admitted for TPL. Those with a long cervix
      (>25 mm) were classified as "inappropriate admissions", and both the economic
      burden based on diagnosis-related group (DRG) and the social costs associated
      with sick leave for these women were calculated. RESULTS: During the 6-year study
      period, 430 women were admitted for TPL. The rate of inappropriate hospital
      admissions was 45% in the first year, but was reduced to 23% in the final year
      (P<0.001); the premature delivery rates in these years did not differ (P=0.224).
      The mean DRG-based cost of the admission per patient with a long cervix was EU
      euros ?2099. The total annual costs from inappropriate admission (both social
      security sick leave costs and hospital costs) were estimated to be up to ?571
      047.37 during the 6-year study period, and reduced from ?60 420.76 in 2009 to ?29
      998.04 in 2014. CONCLUSION: Reductions in inappropriate admissions from applying
      cervical length-based management protocol could reduce healthcare costs without
      increasing the incidence of premature delivery.

PMID- 29369337
TI  - Improving the integrity of published science: An expanded taxonomy of retractions
      and corrections.

PMID- 29369338
TI  - Monocle tumor as tonsillar squamous cell carcinoma metastasis: resolution after
      chemotherapy treatment.

PMID- 29369339
TI  - Prevalence and predictors of depressive symptoms among attendees of a tertiary
      care dermatology clinic in Muscat, Oman.
AB  - BACKGROUND: Various studies have suggested that depression is more prevalent
      among patients with skin disorders than in the general population. Most of the
      studies addressing this subject involve Euro-American populations. OBJECTIVES:
      The present study aimed to estimate the prevalence of depressive symptoms among
      patients with dermatological disorders and, then, to decipher the clinical
      demographic factors associated with depressive symptoms. METHODS: A cross
      sectional analytical study was conducted among a random sample of patients
      attending a dermatology clinic in Muscat. The Patient Health Questionnaire-9 (PHQ
      9) was used to screen for depressive symptoms. A logistic regression model was
      used to find the adjusted and unadjusted odds ratios (ORs). RESULTS: A total of
      260 patients participated in this study, with a response rate of 81%. The
      prevalence of depression symptoms was 24%. According to regression analysis,
      family history of depression, comorbid medical disorders, and treatment with
      topicals or isotretinoin were significant predictors of depression (OR = 9.41,
      95% confidence interval [CI]: 2.27-39.05, P = 0.002; OR = 2.0, 95% CI: 1.2-3.21,
      P = 0.05; OR = 2.28, 95% CI: 1.09-4.76, P = 0.028; and OR = 2.78; 95% CI: 1.08
      7.19, P = 0.035, respectively). CONCLUSION: This study indicates that depressive
      symptoms are common among patients with dermatological disorders in Oman,
      particularly in those with a family history of depression and medical
      comorbidities, and those who use a specific dermatological medication. Screening
      for depression in patients attending dermatology clinics is essential in order to
      detect and promptly treat patients suffering from depression.

PMID- 29369340
TI  - Filaggrin gene mutations may influence the persistence of food allergies in
      Japanese primary school children.

PMID- 29369341
TI  - Monitoring dynamic spatio-temporal ecological processes optimally.
AB  - Population dynamics vary in space and time. Survey designs that ignore these
      dynamics may be inefficient and fail to capture essential spatio-temporal
      variability of a process. Alternatively, dynamic survey designs explicitly
      incorporate knowledge of ecological processes, the associated uncertainty in
      those processes, and can be optimized with respect to monitoring objectives. We
      describe a cohesive framework for monitoring a spreading population that
      explicitly links animal movement models with survey design and monitoring
      objectives. We apply the framework to develop an optimal survey design for sea
      otters in Glacier Bay. Sea otters were first detected in Glacier Bay in 1988 and
      have since increased in both abundance and distribution; abundance estimates
      increased from 5 otters to >5,000 otters, and they have spread faster than 2.7
      km/yr. By explicitly linking animal movement models and survey design, we are
      able to reduce uncertainty associated with forecasting occupancy, abundance, and
      distribution compared to other potential random designs. The framework we
      describe is general, and we outline steps to applying it to novel systems and
      taxa.

PMID- 29369342
TI  - Case report of endometrial cancer with a microcytic, elongated, and fragmented
      pattern of invasion and DNA mismatch repair deficiency.

PMID- 29369343
TI  - Health insurance coverage and access to skilled birth attendance in Togo.
AB  - OBJECTIVE: To examine the effect of the newly introduced national health
      insurance plan on access to skilled birth attendance (SBA). METHODS: The present
      secondary analysis used data from the 2014 Togo Demographic and Health Survey.
      The study sample comprised women aged 15-49 years who had at least one delivery
      in the 5 years preceding the survey. Multivariate logistic regression analyses
      were conducted. RESULTS: The adjusted sample included 4826 women. Overall, 195
      (4.0%) of 4826 pregnant women had health insurance. The coverage rate varied by
      wealth, with poor women having the lowest coverage rate (22/931 [1.1%]).
      Approximately one-third of the women had no SBA at delivery. Women with health
      insurance were almost three times as likely to be assisted by skilled healthcare
      personnel at delivery as were those without health insurance (adjusted odds ratio
      2.74, 95% confidence interval 1.63-4.59). Other factors associated with SBA
      included education, household wealth, and age. CONCLUSION: The study highlights
      the positive impact health insurance coverage could have on access to SBA and
      provides evidence that SBA use could be improved through improved access to
      health insurance. An accessible health insurance scheme will offer a pathway to
      achieving health equity and Sustainable Development Goal 3 in Togo.

PMID- 29369346
TI  - Morphology, diet, and stable carbon isotopes: On the diet of Theropithecus and
      some limits of uniformitarianism in paleoecology.
AB  - Geladas were long supposed to be the only living primates feeding almost entirely
      on graminoids and accordingly display dramatic dental and manual adaptive traits.
      A recent study of Theropithecus gelada, the first in a relatively undisturbed
      habitat, revealed a more diverse diet, also incorporating large quantities of
      forbs. The peculiar adaptive traits of T. gelada are also observed in extinct
      Theropithecus as early as 3.7 Ma. Stable carbon isotopic data of extinct
      Theropithecus from eastern Africa indicate that specimens older than 3 Ma
      consumed a significant proportion of C3 plants (on average ca. 40% of total food
      intake) whereas specimens younger than 2 Ma consumed more C4 plants (on average
      ca. 80%). Recent paleobotanical evidence suggests that C3 herbaceous plants were
      still present in non-negligible proportions in Plio-Pleistocene lowland tropical
      ecosystems. Together, the shared morphological adaptive traits of extant and
      extinct Theropithecus and the varied diets of extant T. gelada suggest that the
      paleodiets of Theropithecus may have been dominated by herbaceous plants,
      comprising both C3 forbs and graminoids and C4 graminoids. The changes in stable
      carbon isotopes could correspond to a replacement of C3 plants by C4 plants
      within the herbaceous strata rather than a shift from C3 woody vegetation to C4
      graminoids. This synthesis highlights the need for a more exhaustive knowledge of
      the ecology of extant species to achieve meaningful paleodietary and
      paleoenvironmental reconstructions. A strong selectivity for food resources that
      are rare in the landscapes (as in T. gelada) should also be considered when
      interpreting stable carbon isotopes of extinct African mammals (and notably
      hominids).

PMID- 29369345
TI  - Circulating plasmablasts are elevated and produce pathogenic anti-endothelial
      cell autoantibodies in idiopathic pulmonary arterial hypertension.
AB  - Idiopathic pulmonary arterial hypertension (IPAH) is a devastating pulmonary
      vascular disease in which autoimmune and inflammatory phenomena are implicated. B
      cells and autoantibodies have been associated with IPAH and identified as
      potential therapeutic targets. However, the specific populations of B cells
      involved and their roles in disease pathogenesis are not clearly defined. We
      aimed to assess the levels of activated B cells (plasmablasts) in IPAH, and to
      characterize recombinant antibodies derived from these plasmablasts. Blood
      plasmablasts are elevated in IPAH, remain elevated over time, and produce IgA
      autoantibodies. Single-cell sequencing of plasmablasts in IPAH revealed
      repertoires of affinity-matured antibodies with small clonal expansions,
      consistent with an ongoing autoimmune response. Recombinant antibodies
      representative of these clonal lineages bound known autoantigen targets and
      displayed an unexpectedly high degree of polyreactivity. Representative IPAH
      plasmablast recombinant antibodies stimulated human umbilical vein endothelial
      cells to produce cytokines and overexpress the adhesion molecule ICAM-1.
      Together, our results demonstrate an ongoing adaptive autoimmune response
      involving IgA plasmablasts that produce anti-endothelial cell autoantibodies in
      IPAH. These antibodies stimulate endothelial cell production of cytokines and
      adhesion molecules, which may contribute to disease pathogenesis. These findings
      suggest a role for mucosally-driven autoimmunity and autoimmune injury in the
      pathogenesis of IPAH.

PMID- 29369347
TI  - Long-term pediatric skin eruption-related hospitalizations in offspring conceived
      via fertility treatment.
AB  - BACKGROUND: Although concerns have been raised regarding the long-term health
      risks of offspring conceived following fertility treatments, limited information
      is available regarding their health status beyond the neonatal period. We aimed
      to evaluate the risk of long-term eruptive dermatological morbidity among
      children born following fertility treatments as compared to those conceived
      spontaneously. METHODS: A population-based cohort study was conducted, including
      all singleton deliveries occurring between the years 1991 and 2014 at a single
      tertiary medical center. Fetuses with congenital malformations and multiple
      gestations were excluded. Children delivered following fertility treatment
      pregnancies and spontaneous pregnancies were compared. Hospitalizations of the
      offspring up to the age of 18 years involving cutaneous eruptions were evaluated.
      A Kaplan-Meier survival curve was used to compare cumulative morbidity incidence
      and a Cox regression model to control for confounders. RESULTS: During the study
      period, 242,187 singleton deliveries met the inclusion criteria, 1.8% of which
      were following fertility treatments (n = 4324). Eruptive dermatological morbidity
      of the offspring up to the age of 18 years was significantly more common in the
      fertility treatment group (1.5%) as compared to spontaneous pregnancies (1.1%; P
      = 0.023). The Kaplan-Meier survival curve demonstrated a significantly higher
      cumulative incidence of eruptive dermatological morbidity following fertility
      treatments (log-rank P = 0.007). Using the Cox regression model, while
      controlling for multiple confounders, fertility treatment was noted as an
      independent risk factor for long-term pediatric eruptive dermatological morbidity
      (adjusted HR = 1.43, CI 1.12-1.83, P = 0.004). CONCLUSION: Singletons conceived
      via fertility treatments appear to be at an increased risk for long-term eruptive
      dermatological morbidity.

PMID- 29369349
TI  - The apelin receptor influences biomechanical and morphological properties of
      endothelial cells.
AB  - The adaption of endothelial cells to local flow conditions is a multifunctional
      process which leads to distinct alterations in cell shape, the subcellular
      distribution of structural proteins, and cellular function. G-protein-coupled
      receptors (GPCRs) have been identified to be fundamentally involved in such
      processes. Recently, we and others have shown that the expression of the
      endothelial GPCR apelin receptor (APJ) is regulated by fluid flow and that
      activation of APJ participates in signaling pathways which are related to
      processes of mechanotransduction. The present study aims to illuminate these
      findings by further visualization of APJ function. We show that APJ is located to
      the cellular junctions and might thus be associated with platelet endothelial
      cell adhesion molecule-1 (PECAM-1) in human umbilical vein endothelial cells
      (HUVEC). Furthermore, siRNA-mediated silencing of APJ expression influences the
      shear-induced adaption of HUVEC in terms of cytoskeletal remodeling, cellular
      elasticity, cellular motility, attachment, and distribution of adhesion
      complexes. Taken together, our results demonstrate that APJ is crucial for
      complemented endothelial adaption to local flow conditions.

PMID- 29369348
TI  - Efficacy and safety of eslicarbazepine acetate versus controlled-release
      carbamazepine monotherapy in newly diagnosed epilepsy: A phase III double-blind,
      randomized, parallel-group, multicenter study.
AB  - OBJECTIVE: We assessed the efficacy and safety of once-daily eslicarbazepine
      acetate in comparison with twice-daily (BID) controlled-release carbamazepine
      (carbamazepine-CR) monotherapy in newly diagnosed focal epilepsy patients.
      METHODS: This randomized, double-blind, noninferiority trial (NCT01162460)
      utilized a stepwise design with 3 dose levels. Patients who remained seizure-free
      for the 26-week evaluation period (level A: eslicarbazepine acetate 800
      mg/carbamazepine-CR 200 mg BID) entered a 6-month maintenance period. If a
      seizure occurred during the evaluation period, patients were titrated to the next
      target level (level B: eslicarbazepine acetate 1200 mg/carbamazepine-CR 400 mg
      BID, level C: eslicarbazepine acetate 1600 mg/carbamazepine-CR 600 mg BID) and
      the evaluation period began again. The primary endpoint was the proportion of
      seizure-free patients for 6 months after stabilization in the per protocol set.
      The predefined noninferiority criteria were -12% absolute and -20% relative
      difference between treatment groups. RESULTS: Eight hundred fifteen patients were
      randomly assigned; 785 (388 in the eslicarbazepine acetate group and 397 in the
      carbamazepine-CR group) were included in the per protocol set, and 813 (401 in
      the eslicarbazepine acetate group and 412 in the carbamazepine-CR group) were
      included in the full analysis set for the primary analysis. Overall, 71.1% of
      eslicarbazepine acetate-treated patients and 75.6% of carbamazepine-CR-treated
      patients were seizure-free for >=6 months at the last evaluated dose (average
      risk difference = -4.28%, 95% confidence interval [CI] = -10.30 to 1.74; relative
      risk difference = -5.87%, 95% CI = -13.50 to 2.44) in the per protocol set. Rates
      of treatment-emergent adverse events were similar between groups for patients in
      the safety set. Noninferiority was also demonstrated in the full analysis set, as
      70.8% of patients with eslicarbazepine acetate and 74.0% with carbamazepine-CR
      were seizure-free at the last evaluated dose (average risk difference = -3.07,
      95% CI = -9.04 to 2.89). SIGNIFICANCE: Treatment with eslicarbazepine acetate was
      noninferior to BID carbamazepine-CR. With its once-daily formulation,
      eslicarbazepine acetate provides a useful option for first-line monotherapy for
      adults with newly diagnosed epilepsy and focal onset seizures.

PMID- 29369350
TI  - Identification and molecular docking study of novel angiotensin-converting enzyme
      inhibitory peptides from Salmo salar using in silico methods.
AB  - BACKGROUND: In order to circumvent some challenges of the classical approach, the
      in silico method has been applied to the discovery of angiotensin-converting
      enzyme (ACE) inhibitory peptides from food proteins. In this study, some
      convenient and efficient in silico tools were utilized to identify novel ACE
      inhibitory peptides from Salmo salar. RESULTS: Collagen from Salmo salar was
      digested in silico into hundreds of peptides. Results revealed that tetrapeptides
      PGAR and IGPR showed potent ACE inhibitory activity, with IC50 values of 0.598 +/
      0.12 and 0.43 +/- 0.09 mmol L-1 , respectively. The molecular docking result
      showed that PGAR and IGPR interact with ACE mostly via hydrogen bonds and
      attractive charge. Peptide IGPR interacts with Zn+ at the ACE active site,
      showing high inhibitory activity. CONCLUSION: Interaction with Zn+ in ACE may
      lead to higher inhibitory activity of peptides, and Pi interactions may promote
      the effect of peptides on ACE. The in silico method can be an effective method to
      predict potent ACE inhibitory peptides from food proteins. (c) 2018 Society of
      Chemical Industry.

PMID- 29369351
TI  - The role of plant mycorrhizal type and status in modulating the relationship
      between plant and arbuscular mycorrhizal fungal communities.
AB  - Interactions between communities of plants and arbuscular mycorrhizal (AM) fungi
      shape fundamental ecosystem properties. Experimental evidence suggests that
      compositional changes in plant and AM fungal communities should be correlated,
      but empirical data from natural ecosystems are scarce. We investigated the
      dynamics of covariation between plant and AM fungal communities during three
      stages of grassland succession, and the biotic and abiotic factors shaping these
      dynamics. Plant communities were characterised using vegetation surveys. AM
      fungal communities were characterised by 454-sequencing of the small subunit rRNA
      gene and identification against the AM fungal reference database MaarjAM. AM
      fungal abundance was estimated using neutral-lipid fatty acids (NLFAs).
      Multivariate correlation analysis (Procrustes) revealed a significant
      relationship between plant and AM fungal community composition. The strength of
      plant-AM fungal correlation weakened during succession following cessation of
      grassland management, reflecting changes in the proportion of plants exhibiting
      different AM status. Plant-AM fungal correlation was strong when the abundance of
      obligate AM plants was high, and declined as the proportion of facultative AM
      plants increased. We conclude that the extent to which plants rely on AM
      symbiosis can determine how tightly communities of plants and AM fungi are
      interlinked, regulating community assembly of both symbiotic partners.

PMID- 29369352
TI  - Monitoring Shelf Life of Pasteurized Whole Milk Under Refrigerated Storage
      Conditions: Predictive Models for Quality Loss.
AB  - : The shelf life of pasteurized milk is generally determined through
      microbiological analysis. The objective of this study was to correlate microbial
      quality parameters then to design predictive models for shelf life of pasteurized
      milk. We analyzed pasteurized milk (3.9% fat) for aerobic plate counts (APCs),
      psychrotrophic bacteria counts (PBCs), and Bacillus spp. counts at 5, 7, 10, 13,
      15, and 19 (+/-1  degrees C) to the end of storage time. We also monitored
      titratable acidity, pH, and, lipase, and protease activity and correlated this
      with APC, which is the principal index defining shelf life. Results indicate that
      the shelf life of pasteurized milk was 24, 36, and 72 h at 19, 15, and 13 
      degrees C respectively, as determined by APC and acidity indicators. However,
      milk stored at lower temperatures of 5, 7, and 10  degrees C had longer shelf
      life of 30, 24, and 12 d, respectively. A sharp increase in titratable acidity,
      while decrease pH were observed when APCs reached 5.0 log10 CFU/mL at all storage
      temperatures. Lipase and protease activities increased with storage temperature.
      At 5 and 7  degrees C, however, protease activity was very low. Therefore, we
      eliminated this parameter from our quality parameters as a potential spoilage
      indicator. PRACTICAL APPLICATION: Findings of this research are useful for
      monitoring the quality of commercial pasteurized milk, particularly in locations
      where environmental conditions make longer storage difficult. The study also
      provides valuable information for development of colorimetric shelf life
      indicators.

PMID- 29369353
TI  - Spin-coated epoxy resin embedding technique enables facile SEM/FIB thickness
      determination of porous metal oxide ultra-thin films.
AB  - A facile nonsubjective method was designed to measure porous nonconductive iron
      oxide film thickness using a combination of a focused ion beam (FIB) and scanning
      electron microscopy. Iron oxide films are inherently nonconductive and porous,
      therefore the objective of this investigation was to optimize a methodology that
      would increase the conductivity of the film to facilitate high resolution imaging
      with a scanning electron microscopy and to preserve the porous nature of the film
      that could potentially be damaged by the energy of the FIB. Sputter coating the
      sample with a thin layer of iridium before creating the cross section with the
      FIB decreased sample charging and drifting, but differentiating the iron layer
      from the iridium coating with backscattered electron imaging was not definitive,
      making accurate assumptions of the delineation between the two metals difficult.
      Moreover, the porous nature of the film was lost due to beam damage following the
      FIB process. A thin layer plastication technique was therefore used to embed the
      porous film in epoxy resin that would provide support for the film during the FIB
      process. However, the thickness of the resin created using conventional thin
      layer plastication processing varied across the sample, making the measuring
      process only possible in areas where the resin layer was at its thinnest. Such
      variation required navigating the area for ideal milling areas, which increased
      the subjectivity of the process. We present a method to create uniform thin resin
      layers, of controlled thickness, that are ideal for quantifying the thickness of
      porous nonconductive films with FIB/scanning electron microscopy.

PMID- 29369354
TI  - The role of nitric oxide in the cardiopulmonary response to hypoxia in highland
      and lowland newborn llamas.
AB  - KEY POINTS: Perinatal hypoxia causes pulmonary hypertension in neonates,
      including humans. However, in species adapted to hypoxia, such as the llama,
      there is protection against pulmonary hypertension. Nitric oxide (NO) is a
      vasodilatator with an established role in the cardiopulmonary system of many
      species, but its function in the hypoxic pulmonary vasoconstrictor response in
      the newborn llama is unknown. Therefore, we studied the role of NO in the
      cardiopulmonary responses to acute hypoxia in high- and lowland newborn llamas.
      We show that high- compared to lowland newborn llamas have a reduced pulmonary
      vasoconstrictor response to acute hypoxia. Protection against excessive pulmonary
      vasoconstriction in the highland llama is mediated via enhancement of NO
      pathways, including increased MYPT1 and reduced ROCK expression as well as Ca2+
      desensitization. Blunting of pulmonary hypertensive responses to hypoxia through
      enhanced NO pathways may be an adaptive mechanism to withstand life at high
      altitude in the newborn llama. ABSTRACT: Llamas are born in the Alto Andino with
      protection against pulmonary hypertension. The physiology underlying protection
      against pulmonary vasoconstrictor responses to acute hypoxia in highland species
      is unknown. We determined the role of nitric oxide (NO) in the cardiopulmonary
      responses to acute hypoxia in high- and lowland newborn llamas. The
      cardiopulmonary function of newborn llamas born at low (580 m) or high altitude
      (3600 m) was studied under acute hypoxia, with and without NO blockade. In
      pulmonary arteries, we measured the reactivity to potassium and sodium
      nitroprusside (SNP), and in lung we determined the content of cGMP and the
      expression of the NO-related proteins: BKCa, PDE5, PSer92-PDE5, PKG-1, ROCK1 and
      2, MYPT1, PSer695-MYPT1, PThr696-MYPT1, MLC20 and PSer19-MLC20. Pulmonary
      vascular remodelling was evaluated by morphometry and based on alpha-actin
      expression. High- compared to lowland newborn llamas showed lower in vivo
      pulmonary arterial pressor responses to acute hypoxia. This protection involved
      enhanced NO function, as NO blockade reverted the effect and the pulmonary
      arterial dilatator response to SNP was significantly enhanced in highland
      neonates. The pulmonary expression of ROCK2 and the phosphorylation of MLC20 were
      lower in high-altitude llamas. Conversely, MYPT1 was up-regulated whilst PSer695
      MYPT1 and PThr695-MYPT1 did not change. Enhanced NO-dependent mechanisms were
      insufficient to prevent pulmonary arterial remodelling. Combined, the data
      strongly support that in the highland newborn llama reduced ROCK, increased MYPT1
      expression and Ca2+ desensitization in pulmonary tissue allow an enhanced NO
      biology to limit hypoxic pulmonary constrictor responses. Blunting of hypoxic
      pulmonary hypertensive responses may be an adaptive mechanism to life at high
      altitude.

PMID- 29369355
TI  - Recent advances in postharvest technology of the wine grape to improve the wine
      aroma.
AB  - Postharvest techniques are widely used for the handling and storage of fresh
      horticultural crops. Some of these techniques are interesting for use with wine
      grapes to improve the quality of wine. In this review, we consider the
      postharvest techniques that are already commercially used in the wine sector and
      others that may be significant in inducing or extracting the aroma from grapes to
      produce high-quality wines. Precooling consists of rapidly lowering the grape
      temperature, which allows the preservation/increase of volatile organic compounds
      (VOCs). We also discuss sustainability. Partial dehydration consists of the
      partial removal of water from grapes, and if a suitable environment is adopted it
      can be used to produce and extract berry VOCs. As a solid, carbon dioxide is used
      in wine processing for the rapid cooling of grapes and, as a gas, it is used for
      carbonic maceration. Ozone has been used for sanitation purposes in wineries for
      a long time, but more recently it has been used to produce wine without sulfite
      addition and to increase the aromatic quality of wine grapes. Ethylene
      application is not used commercially for wine grapes, but promising results in
      terms of phenolic extraction and aromatic changes in grapes are discussed. A
      comparison among the proposed techniques is reported in terms of grape aromatic
      quality and process features. The proposed techniques could help a winemaker to
      maintain or induce aromatic compounds in grape berries before the vinification
      process. The choice depends on the desired wine and economic consistency. (c)
      2018 Society of Chemical Industry.

PMID- 29369356
TI  - Hypertonicity-induced cation channels in HepG2 cells: architecture and role in
      proliferation vs. apoptosis.
AB  - KEY POINTS: Na+ conducting hypertonicity-induced cation channels (HICCs) are key
      players in the volume restoration of osmotically shrunken cells and, under
      isotonic conditions, considered as mediators of proliferation - thereby opposing
      apoptosis. In an siRNA screen of ion channels and transporters in HepG2 cells,
      with the regulatory volume increase (RVI) as read-out, deltaENaC, TRPM2 and TRPM5
      were identified as HICCs. Subsequently, all permutations of these channels were
      tested in RVI and patch-clamp recordings and, at first sight, HICCs were found to
      operate in an independent mode. However, there was synergy in the siRNA
      perturbations of HICC currents. Accordingly, proximity ligation assays showed
      that deltaENaC was located in proximity to TRPM2 and TRPM5 suggesting a physical
      interaction. Furthermore, deltaENaC, TRPM2 and TRPM5 were identified as mediators
      of HepG2 proliferation - their silencing enhanced apoptosis. Our study defines
      the architecture of HICCs in human hepatocytes as well as their molecular
      functions. ABSTRACT: Hypertonicity-induced cation channels (HICCs) are a
      substantial element in the regulatory volume increase (RVI) of osmotically
      shrunken cells. Under isotonic conditions, they are key effectors in the volume
      gain preceding proliferation; HICC repression, in turn, significantly increases
      apoptosis rates. Despite these fundamental roles of HICCs in cell physiology,
      very little is known concerning the actual molecular architecture of these
      channels. Here, an siRNA screening of putative ion channels and transporters was
      performed, in HepG2 cells, with the velocity of RVI as the read-out; in this
      first run, deltaENaC, TRPM2 and TRPM5 could be identified as HICCs. In the second
      run, all permutations of these channels were tested in RVI and patch-clamp
      recordings, with special emphasis on the non-additivity and additivity of siRNAs 
      which would indicate molecular interactions or independent ways of channel
      functioning. At first sight, the HICCs in HepG2 cells appeared to operate rather
      independently. However, a proximity ligation assay revealed that deltaENaC was
      located in proximity to both TRPM2 and TRPM5. Furthermore, a clear synergy of
      HICC current knock-downs (KDs) was observed. deltaENaC, TRPM2 and TRPM5 were
      defined as mediators of HepG2 cell proliferation and their silencing increased
      the rates of apoptosis. This study provides a molecular characterization of the
      HICCs in human hepatocytes and of their role in RVI, cell proliferation and
      apoptosis.

PMID- 29369357
TI  - Development of an automated flow injection analysis system for determination of
      phosphate in nutrient solutions.
AB  - BACKGROUND: A fully automated flow injection analysis (FIA) system was developed
      for determination of phosphate ion in nutrient solutions. This newly developed
      FIA system is a portable, rapid and sensitive measuring instrument that allows on
      line analysis and monitoring of phosphate ion concentration in nutrient
      solutions. The molybdenum blue method, which is widely used in FIA phosphate
      analysis, was adapted to the developed FIA system. The method is based on the
      formation of ammonium Mo(VI) ion by reaction of ammonium molybdate with the
      phosphate ion present in the medium. The Mo(VI) ion then reacts with ascorbic
      acid and is reduced to the spectrometrically measurable Mo(V) ion. New software
      specific for flow analysis was developed in the LabVIEW development environment
      to control all the components of the FIA system. The important factors affecting
      the analytical signal were identified as reagent flow rate, injection volume and
      post-injection flow path length, and they were optimized using Box-Behnken
      experimental design and response surface methodology. RESULTS: The optimum point
      for the maximum analytical signal was calculated as 0.50 mL min-1 reagent flow
      rate, 100 uL sample injection volume and 60 cm post-injection flow path length.
      The proposed FIA system had a sampling frequency of 100 samples per hour over a
      linear working range of 3-100 mg L-1 (R2  = 0.9995). The relative standard
      deviation (RSD) was 1.09% and the limit of detection (LOD) was 0.34 mg L-1 .
      CONCLUSION: Various nutrient solutions from a tomato-growing hydroponic
      greenhouse were analyzed with the developed FIA system and the results were found
      to be in good agreement with vanadomolybdate chemical method findings. (c) 2018
      Society of Chemical Industry.

PMID- 29369358
TI  - The association between weight gain during pregnancy and intertwin delivery
      weight discordance using 2011-2015 birth registration data from the USA.
AB  - OBJECTIVE: To assess the effect of weight gain during pregnancy on intertwin
      delivery weight discordance. METHODS: In the present retrospective cohort study
      using twin delivery records, data were extracted from the 2011-2015 USA birth
      registration dataset created by the Centers for Disease Control and Prevention.
      The outcome variable was delivery weight discordance. The nonlinear association
      of weight gain during pregnancy with delivery weight discordance was examined
      using a generalized additive model, adjusting for potential confounders. RESULTS:
      A total of 255 627 twin pairs were included in this analysis. Weight gain during
      pregnancy showed an inverse, yet nonlinear, association with intertwin delivery
      weight discordance. Women with weight gain of approximately 25 kg exhibited the
      lowest level of discordance. When stratified by pre-pregnancy body mass index,
      the association of weight gain with discordance became insignificant among obese
      women. When categorizing weight gain according to recommendations from the
      Institute of Medicine, inadequate weight gain was associated with increased risk
      of discordance among women of any pre-pregnancy body mass index. CONCLUSION: Twin
      pregnancies with maternal weight gain of approximately 25 kg demonstrated the
      lowest risk of developing intertwin delivery weight discordance, while inadequate
      weight gain was a risk factor for delivery weight discordance in all pre
      pregnancy body mass index categories.

PMID- 29369359
TI  - Fruit flesh volatile and carotenoid profile analysis within the Cucumis melo L.
      species reveals unexploited variability for future genetic breeding.
AB  - BACKGROUND: Aroma profile and carotenoids content of melon flesh are two
      important aspects influencing the quality of this fruit that have been
      characterized using only selected genotypes. However, the extant variability of
      the whole species remains unknown. RESULTS: A complete view of the
      volatile/carotenoid profiles of melon flesh was obtained analyzing 71 accessions,
      representing the whole diversity of the species. Gas chromatography-mass
      spectrometry and high-performance liquid chromatography were used to analyze 200
      volatile compounds and five carotenoids. Genotypes were classified into two main
      clusters (high/low aroma), but with a large diversity of differential profiles
      within each cluster, consistent with the ripening behavior, flesh color and
      proposed evolutionary and breeding history of the different horticultural groups.
      CONCLUSION: Our results highlight the huge amount of untapped aroma diversity of
      melon germplasm, especially of non-commercial types. Also, landraces with high
      nutritional value with regard to carotenoids have been identified. All this
      knowledge will encourage melon breeding, facilitating the selection of the
      genetic resources more appropriate to develop cultivars with new aromatic
      profiles or to minimize the impact of breeding on melon quality. The newly
      characterized sources provide the basis for further investigations into specific
      genes/alleles contributing to melon flesh quality. (c) 2018 Society of Chemical
      Industry.

PMID- 29369360
TI  - Efficacy of Peracetic Acid in Inactivating Foodborne Pathogens on Fresh Produce
      Surface.
AB  - : Washing treatment with effective sanitizer is one of the critical steps in
      ensuring fresh produce safety. This study was to evaluate the efficacy of
      peracetic acid (PAA; VigorOx(r) 15 F&V), chlorine-based sanitizers (acidic
      electrolyzed water [AEO], near neutral electrolyzed water and bleach), lactic
      acid, and deionized (DI) water to reduce Escherichia coli O157:H7, Listeria
      monocytogenes, and Salmonella Typhimurium DT104 from fresh produce surfaces. A 5
      strain cocktail of E. coli O157:H7, L. monocytogenes, and S. Typhimurium DT104
      was separately prepared and used for surface inoculation on produce samples (E.
      coli O157:H7 on romaine lettuce, lemons, tomatoes, and blueberries; L.
      monocytogenes on romaine lettuce and cantaloupe; S. Typhimurium DT104 on lemons,
      tomatoes, cantaloupe, and blueberries). PAA at 45, 85, and 100 mg/L; AEO, NNEO,
      and bleach at 100 mg/L of free chlorine; lactic acid at 2%; and DI water were
      used for washing inoculated produce in an automated produce washer for 5 min. In
      general, PAA at 100 mg/L achieved the highest microbial inactivation of E. coli
      O157:H7 (lettuce, lemon, tomato, and blueberry at 2.2, 5.7, 5.5, and 6.7 log
      CFU/g, respectively), S. Typhimurium DT104 (lemon, tomato, cantaloupe, blueberry
      at 5.4, 6.8, 4.5, and 5.9 log CFU/g, respectively), and L. monocytogenes (lettuce
      and cantaloupe at 2.4 and 4.4 log CFU/g, respectively). Efficacy of sanitizers on
      produce with coarse surface (for example, lettuce and cantaloupe) was lower than
      produce with smooth texture (lemon, tomato, and blueberry). Cross-contamination
      of E. coli O157:H7 among romaine lettuce heads during simulated retail crisping
      process was greatly reduced by the application of PAA and NNEO. PRACTICAL
      APPLICATION: NNEO and PAA showed high efficacy in foodborne pathogen removal from
      fresh produce. Produce surface texture plays an important role in pathogen
      removal. NNEO and PAA effectively prevented cross-contamination during the
      crisping process.

PMID- 29369361
TI  - Influence of Food with High Moisture Content on Oxygen Barrier Property of
      Polyvinyl Alcohol (PVA)/Vermiculite Nanocomposite Coated Multilayer Packaging
      Film.
AB  - : This study investigates the potential complications in applying nanoclay-based
      waterborne coating to packaging films for food with high moisture content.
      Multilayer packaging films were prepared by dry laminating commercially available
      polyvinyl alcohol (PVA)/vermiculite nanocomposite coating films and linear low
      density polyethylene film, and the changes in oxygen barrier properties were
      investigated according to different relative humidity using 3 types of food
      simulants. When the relative humidity was above 60%, the oxygen permeability
      increased sharply, but this was reversible. Deionized water and 3% acetic acid
      did not cause any large structural change in the PVA/vermiculite nanocomposite
      but caused a reversible deterioration of the oxygen barrier properties. In
      contrast, 50% ethanol, a simulant for the semifatty food, induced irreversible
      structural changes with deterioration of the oxygen barrier property. These
      changes are due to the characteristics of PVA rather than vermiculite. PRACTICAL
      APPLICATION: We believe this manuscript would be of interest to the wide group of
      researchers, organizations, and companies in the field of developing nanoclay
      based gas barrier packaging for foods with high moisture content. Hence, we wish
      to diffuse our knowledge to the scientific community.

PMID- 29369362
TI  - Influence of Selected Saccharomyces and Schizosaccharomyces Strains and Their
      Mixed Cultures on Chemical Composition of Apple Wines.
AB  - : Currently in apple winemaking, pure cultures of Saccharomyces cerevisiae and S.
      bayanus strains are mainly used. The aim of this study was to determine the
      influence of Saccharomyces cerevisiae (Johannisberg Riesling - LOCK 105), S.
      bayanus (DSMZ 3774), S. paradoxus (CBS 7302), and Schizosaccharomyces pombe (DSMZ
      70576) applied in pure and mixed cultures on the chemical composition and sensory
      profile of apple wines. Pasteurized Gloster apple musts with addition of sucrose
      (up to 22 degrees Blg) were inoculated with specific volume (0.6 g dry weight per
      liter) of yeast pure or mixed cultures (in a ratio of 1:1, 1:1:1, or 1:1:1:1) and
      fermented for 28 d at 22  degrees C. The influence of pure/mixed culture on the
      chemical composition, volatile profile, and sensory properties of apple wines was
      determined using high-performance liquid chromatography (HPLC) and gas
      chromatography (GC) methods. All pure culture of yeasts used for the apple wines
      production are characterized by good enological profiles. S. bayanus and Sch.
      pombe are the most distinct to S. cerevisiae. S. bayanus strain increases the
      level of malic acid and carbonyl compounds in apple wines, whereas Sch. pombe
      highly deacidifies it and produces the most of glycerol, esters, and acetic acid.
      The wines obtained with these 2 species gained also, respectively, the best and
      the worse notes during sensory analysis. Mixed cultures (in most cases) produce
      greater amounts of ethanol, methanol, and volatile esters compared to pure
      cultures. The presence of S. bayanus in the mixed culture is beneficial for the
      quality of apple wines. PRACTICAL APPLICATION: Good understanding of the
      properties of yeasts and the procedures for their selection will make it easier
      to find strains that could improve the quality of wine. Since wine is formed by
      the action of a number of species and strains of yeasts, many authors have
      studied the effect of mixed cultures on the final quality of the product. Most of
      this research was focused on the effect of the inoculation of Saccharomyces yeast
      with other species on the aroma of wine. However, there is a little data on the
      fermentation using simultaneous inoculation of different strains of S.
      cerevisiae.

PMID- 29369363
TI  - Comparison of Cinnamon Essential Oils from Leaf and Bark with Respect to
      Antimicrobial Activity and Sensory Acceptability in Strawberry Shake.
AB  - : Cinnamon leaf and bark essential oils have long been used as natural
      preservatives and flavoring agents in foods. This study determined antimicrobial
      effects of leaf and bark of cinnamon essential oils (CEOs) against 2 foodborne
      pathogens, Salmonella Typhimurium (S.T.) and Listeria monocytogenes (L.m.), at 2
      initial bacterial levels (4- and 9-log CFU/mL) in strawberry shakes. The
      antimicrobial study of CEOs at 0.1% and 0.5% in strawberry shakes against S.T.
      and L.M. showed a significant difference (P < 0.05) in log reductions of both
      bacterial growth at low (4-log CFU/mL) and high (9-log CFU/mL) initial bacterial
      levels. Addition of 0.5% CEOs into strawberry shakes at 4  degrees C completely
      inhibited both bacteria after a period of 8 d storage. Shelf-life study showed
      that acidity and total solid content were not affected during storage. The
      strawberry shakes containing bark CEO had higher ratings of sensory acceptability
      compared to leaf CEO, with or without the addition of 1% masking agent. In
      conclusion, this study demonstrated that CEO derived from bark was better than
      that from leaf in terms of their antimicrobial activity and sensory aspect.
      PRACTICAL APPLICATION: This study demonstrates that essential oils derived from
      cinnamon bark and leaf have the potential to be used as natural antimicrobial
      ingredient in milk beverages with respect to sensory aspect. This finding
      promotes the acceptance of natural antimicrobials among consumers, while
      providing enhanced safer products to the food industry application.

PMID- 29369364
TI  - Explorative analysis of IPA-SPECT data through statistical inference for an
      automated diagnosis of glioma tumor.
AB  - PURPOSE: The identification of a brain tumor imaged with PET or SPECT is usually
      performed with visual inspection of an expert medical clinician. However an
      automated diagnostic of such images hasn't been established or applied. In this
      study, we explored the possibility of establishing an automated statistical
      analysis for the diagnosis of glioma by means of IPA-SPECT data. METHODS: On the
      basis of a dataset of 100 patients that have undergone MRI and IPA-SPECT
      acquisition, in this work, we identify an automated workflow. Three different
      approaches were explored: I. statistical non-parametric mapping analysis (SnPM),
      II. statistical non-parametric analysis with an increased number of permutations
      due to sign-flipping function (PALM) and III. statistical parametric analysis
      (SPM). The automated methods were compared with the visual inspection. RESULTS:
      The study proved PALM and SPM approaches to have a high diagnostic power.
      Compared to the parametric methods, the non-parametric method is the
      mathematically correct approach for the problem in question. If we take the high
      resolution structural MRI information into account, the diagnostic power of PALM
      was not significantly inferior to the visual inspection (P = 0.5150), showing an
      area under the ROC curve (AUC) smaller only by less than 3%. CONCLUSIONS: The
      automated diagnostic method based on statistical inference, here applied to
      diagnose glioma tumors in IPA-SPECT data, seems to be a promising tool that can
      support the visual investigation in nuclear medicine. Moreover in the foreseeable
      future, the presented methodology has a big potential in various application like
      localization of active tumor tissues in surgical resection or stereotactic
      radiosurgery.

PMID- 29369365
TI  - Spectroscopic identification of individual fluorophores using photoluminescence
      excitation spectra.
AB  - The identity of a fluorophore can be ambiguous if other fluorophores or
      nonspecific fluorescent impurities have overlapping emission spectra. The
      presence of overlapping spectra makes it difficult to differentiate fluorescent
      species using discrete detection channels and unmixing of spectra. The unique
      absorption and emission signatures of fluorophores provide an opportunity for
      spectroscopic identification. However, absorption spectroscopy may be affected by
      scattering, whereas fluorescence emission spectroscopy suffers from signal loss
      by gratings or other dispersive optics. Photoluminescence excitation spectra,
      where excitation is varied and emission is detected at a fixed wavelength, allows
      hyperspectral imaging with a single emission filter for high signal-to-background
      ratio without any moving optics on the emission side. We report a high throughput
      method for measuring the photoluminescence excitation spectra of individual
      fluorophores using a tunable supercontinuum laser and prism-type total internal
      reflection fluorescence microscope. We used the system to measure and sort the
      photoluminescence excitation spectra of individual Alexa dyes, fluorescent
      nanodiamonds (FNDs), and fluorescent polystyrene beads. We used a Gaussian
      mixture model with maximum likelihood estimation to objectively separate the
      spectra. Finally, we spectroscopically identified different species of
      fluorescent nanodiamonds with overlapping spectra and characterized the
      heterogeneity of fluorescent nanodiamonds of varying size.

PMID- 29369366
TI  - Electrophysiological characteristics and catheter ablation of symptomatic focal
      premature atrial contractions originating from pulmonary veins and non-pulmonary
      veins.
AB  - BACKGROUND: We aimed to explore electrophysiological characteristics of premature
      atrial contractions (PACs) originating from pulmonary veins (PVs) and non-PVs and
      to evaluate the effectiveness and safety of catheter ablation for PACs.
      HYPOTHESIS: Symptomatic PACs originated from different positions and whether
      could be ablated. METHODS: Symptomatic, frequent, and drug-refractory PAC
      patients were enrolled in this study. All patients underwent electrophysiological
      study and catheter ablation. RESULTS: A total of 81 patients were enrolled: 45
      patients with PACs originating from PVs (group A), 24 patients with PACs
      originating from non-PVs (group B), and 12 patients with PACs arising from both
      PVs and non-PVs (group C). Twenty (44.4%) patients in group A, 6 (50.0%) patients
      in group C, and 3 (12.5%) patients in group B presented paroxysmal atrial
      fibrillation (P < 0.05). PV isolation was performed in groups A and C. Focal
      ablation or superior vena cava isolation was performed in groups B and C,
      depending on patient condition. PACs were abolished in all patients except one
      patient in group B. During a median follow-up period of 21.3 +/- 14.3 months, 40
      (88.9%) patients in group A, 10 (83.3%) patients in group C, and 21 (87.5%)
      patients in group B were free of recurrence after initial ablation. CONCLUSIONS:
      Frequent PACs originating from PVs were associated with increased incidence of
      atrial fibrillation compared with PACs originating from non-PVs. Catheter
      ablation yields a satisfactory success rate and could be a good choice for
      eliminating symptomatic, frequent, and drug-refractory PACs.

PMID- 29369367
TI  - Development of a stiffness-angle law for simplifying the measurement of human
      hair stiffness.
AB  - OBJECTIVE: This research examines the benefits of caffeine absorption on hair
      stiffness. To test hair stiffness, we have developed an evaluation method that is
      not only accurate, but also inexpensive. Our evaluation method for measuring hair
      stiffness culminated in a model, called the Stiffness-Angle Law, which describes
      the elastic properties of hair and can be widely applied to the development of
      hair care products. METHODS: Small molecules (<=500 g mol-1 ) such as caffeine
      can be absorbed into hair. A common shampoo containing 4% caffeine was formulated
      and applied to hair 10 times, after which the hair stiffness was measured. The
      caffeine absorption of the treated hair was observed using Fourier-transform
      infrared spectroscopy (FTIR) with a focal plane array (FPA) detector. Our
      evaluation method for measuring hair stiffness consists of a regular camera and a
      support for single strands of hair. After attaching the hair to the support, the
      bending angle of the hair was observed with a camera and measured. Then, the hair
      strand was weighed. The stiffness of the hair was calculated based on our
      proposed Stiffness-Angle Law using three variables: angle, weight of hair and the
      distance the hair was pulled across the support. RESULTS: The caffeine absorption
      was confirmed by FTIR analysis. The concentration of amide bond in the hair
      certainly increased due to caffeine absorption. After caffeine was absorbed into
      the hair, the bending angle and weight of the hair changed. Applying these
      measured changes to the Stiffness-Angle Law, it was confirmed that the hair
      stiffness increased by 13.2% due to caffeine absorption. CONCLUSION: The
      theoretical results using the Stiffness-Angle Law agree with the visual
      examinations of hair exposed to caffeine and also the known results of hair
      stiffness from a previous report. Our evaluation method combined with our
      proposed Stiffness-Angle Law effectively provides an accurate and inexpensive
      evaluation technique for measuring bending stiffness of human hair.

PMID- 29369368
TI  - Khat chewing increases the risk for developing chronic liver disease: A hospital
      based case-control study.
AB  - : The chewing of the leaves of Catha edulis (khat) has been implicated in the
      development of liver disease, but no controlled observations have been
      undertaken. The objective of the present study was to determine whether khat
      chewing is associated with development of chronic liver disease (CLD). A case
      control study was conducted at two public hospitals in Harar, Ethiopia, between
      April 2015 and April 2016. A consecutive sample of 150 adult hospital attendees
      with CLD were included as cases, and 300 adult hospital attendees without
      clinical or laboratory evidence of CLD were included as controls. Khat
      consumption was quantified in "khat years"; 1 khat year was defined as daily use
      of 200 g of fresh khat for 1 year. A logistic regression model was used to
      control for confounders. There was a significant association between chewing khat
      and the risk for developing CLD (crude odds ratio, 2.64; 95% confidence interval
      [CI], 1.56-4.58). In men, this risk, following adjustment for age, alcohol use,
      and chronic hepatitis B/C infection, increased with increasing khat exposure;
      thus, compared to never users the adjusted odds ratios were for low khat exposure
      3.58 (95% CI 1.05-12.21), moderate khat exposure 5.90 (95% CI 1.79-19.44), and
      high khat exposure 13.03 (95% CI 3.61-47.02). The findings were robust in a post
      hoc sensitivity analysis in which individuals with identifiable risk factors for
      CLD were excluded. CONCLUSION: A significant association was observed between
      chewing khat and the risk for developing CLD, and in men the association was
      strong and dose-dependent, suggesting a causal relationship; as the prevalence of
      khat chewing is increasing worldwide, these findings have major public health
      implications. (Hepatology 2018;68:248-257).

PMID- 29369369
TI  - Health behaviours and quality of life in independently living South Australians
      aged 75 years or older.
AB  - BACKGROUND: This study evaluated the associations between oral and general health
      behaviours, self-reported health and quality of life of adults aged 75 years or
      older living independently in South Australia. METHODS: A cross sectional study
      based on a self-report mailed questionnaire was conducted in 590 independently
      living adults aged 75 years or older. Self-ratings of oral health and general
      health were assessed using single-item global ratings. Quality of life was
      measured using the Oral Health Impact Profile and the EuroQol instrument for
      health utility. RESULTS: The overall response rate was 78%. The current analyses
      were restricted to 354 dentate older adults. Increasing age and being female were
      negatively associated with EuroQol scores. Good self-rated oral and general
      health were more prevalent in participants with higher social status who also had
      lower oral health impact and higher EuroQol scores. Good self-rated oral and
      general health were less prevalent while oral health impact was greater in
      participants who ate few fruits, vegetables or dairy products. CONCLUSIONS: Self
      rated health and quality of life were poor in older adults with inadequate
      fruit/vegetables/dairy intake and lower social status. These findings suggest
      that nutrition and socioeconomic factors may be important to the oral and general
      health of adults aged 75 years or older.

PMID- 29369370
TI  - Evaluation of QT dispersion and Tp-e interval in children with subclinical
      hypothyroidism.
AB  - BACKGROUND: Studies on adults have shown increased dispersion of QT and corrected
      QT (QTc), peak-to-end interval of the T wave (Tp-e), Tp-e/QT ratio, and Tp-e/QTc
      ratio in subclinical hypothyroidism (SH), but there have been no pediatric
      studies. MATERIALS AND METHODS: A total of 40 SH patients were compared with 40
      healthy children in respect to serum thyroid-stimulating hormone (TSH), serum
      free level of triiodothyronine, and free level of thyroxine (fT4). SH diagnosis
      was accepted as TSH above the laboratory accepted upper limit (>4.2 mU/L) and
      normal fT4 values. The patient and control group data were compared by
      calculating the QT interval, QTc, QT dispersion (QTd), QTc dispersion (QTcd), Tp
      e, Tp-e/QT ratio, and Tp-e/QTc ratio on 12-lead surface electrocardiogram.
      RESULTS: The mean age was 7.91 +/- 3.6 years in the SH group and 8.8 +/- 2.4
      years in the control group. In the SH group, the minimum QT (QTmin) was
      determined to be statistically significantly lower (P < 0.001) and maximum QT
      (QTmax), QTd, QTcd, Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio were statistically
      significantly higher (P = 0.028, P < 0.001, P = 0.003, P < 0.001, P = 0.001, P <
      0.001, respectively). A positive correlation was determined between TSH and QTmax
      (r: +0.331, P = 0.037). CONCLUSIONS: The current study is the first to have shown
      significantly increased QTd, QTcd, Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio in
      children diagnosed with SH. A positive correlation was determined between TSH and
      maximum QT values, Tp-e, Tp-e/QT ratio, and Tp-e/QTc ratio. These results suggest
      the need to further assess the long-term risks of prolonged QT dispersion in the
      setting of subclinical hypothyroidism.

PMID- 29369371
TI  - Clinical outcomes after upgrading from pacemakers to cardiac resynchronization
      therapy.
AB  - BACKGROUND AND AIMS: Right ventricular pacing may lead to heart failure (HF).
      Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded
      from most randomized, controlled trials. We sought to determine the long-term
      outcomes of upgrading from pacemakers to CRT with (CRT-D) or without (CRT-P)
      defibrillation in patients with no history of sustained ventricular arrhythmias.
      METHODS AND RESULTS: In this observational study, clinical events were quantified
      in relation to the type of implant (de novo or upgrade) and device type at
      upgrade (CRT-P or CRT-D). Patients underwent CRT implantation (n = 1,545; 1,314
      [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years
      [interquartile range: 2.4-7.0]. In analyses of crude event rates, upgrades had a
      higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence
      interval [CI] 0.10-1.61), a higher total mortality or HF hospitalization (aHR:
      1.26; 95% CI 1.05-1.51), but similar mortality or hospitalization for major
      adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96-1.38). No group differences
      emerged in any of these endpoints after propensity score matching. After inverse
      probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36-0.73),
      total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34-0.79), and total
      mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40-0.82) were lower
      after CRT-D than after CRT-P. CONCLUSION: Upgrading from pacemakers to CRT was
      associated with a similar long-term risk of mortality and morbidity to de novo
      CRT. After upgrade, CRT-D was associated with a lower mortality than CRT-P.

PMID- 29369372
TI  - Effects of the dopamine D3 receptor agonist 7-hydroxy-2-(di-N-propylamino)
      tetralin in hyperthyroidism-induced premature ejaculation rat model.
AB  - Various factors are involved in the aetiology of premature ejaculation (PE).
      Hyperthyroidism is one of the causes of acquired PE, but the exact mechanism by
      which it causes the disorder is not yet understood. The aim of this study was to
      evaluate the role of the dopaminergic system in hyperthyroidism-induced PE by the
      intracerebroventricular microinjection of the preferentially active dopamine
      receptor agonist 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT) in a rat
      model of this disorder. Wistar rats were randomly divided into hyperthyroid and
      control groups, and ejaculation was induced by the ICV administration of 7-OH
      DPAT. To evaluate the emission and expulsion phases of ejaculation, measurements
      of seminal vesicle pressure (SVP) and electromyographic recordings of the
      bulbospongiosus muscle were taken. The interval between the 7-OH-DPAT
      administration and the first ejaculation was significantly less in the
      hyperthyroid group (p < .01) than in the control group, and the maximum amplitude
      of the SVP values revealed a statistically significant difference between the
      groups (p < .01). The intervals between contractions of the seminal vesicle and
      bulbospongiosus muscles were also significantly less in the hyperthyroid group (p
      = .0187) than in the control group. No other results differed significantly
      between the groups. This study determined that hyperthyroidism altered only the
      emission phase of ejaculation.

PMID- 29369373
TI  - Preclinical approaches to assess potential kinase inhibitor-induced cardiac
      toxicity: Past, present and future.
AB  - Over a decade ago, use of tyrosine kinase inhibitors (TKIs) for the treatment of
      malignancies was found to cause left ventricular dysfunction, a finding that was
      unexpected and not well predicted by standard preclinical studies. Subsequently,
      several preclinical approaches were proposed to address this issue. Over the last
      5 years, several approaches for preclinical evaluation of cardiac function using
      isolated perfused hearts, engineered heart tissue and human-induced pluripotent
      stem cell-derived cardiac myocytes have been shown to be relatively predictive of
      the cardiotoxic potential of TKIs. Further, preclinical studies submitted for
      regulatory review for recently approved KIs have demonstrated various forms of KI
      induced cardiotoxicity. Thus, early identification and assessment of
      cardiotoxicity in the preclinical setting is now possible. Given that kinases are
      involved in diverse cellular processes common to both normal and tumor cells, KI
      induced toxicity, particularly in the heart, appears difficult to avoid. To
      develop drugs with fewer adverse effects, better efficacy and safety assessments,
      such as pharmacological separation of targets for cancer from heart, and/or wider
      separation of the drug concentrations for antitumor activity from cardiac
      toxicity, may be helpful. Additional preclinical approaches for assessing drug
      efficacy and toxicity in parallel may include use of animal cancer models and a
      3D integrated in vitro model of perfused tumor and heart tissues. Minimizing and
      predicting potential KI-induced cardiotoxicity is still an important regulatory
      challenge, and better preclinical approaches may help achieve this goal.

PMID- 29369374
TI  - Fragile lives with fragile rights: Justice for babies born at the limit of
      viability.
AB  - There is an inconsistency in the ways that doctors make clinical decisions
      regarding the treatment of babies born extremely prematurely. Many experts now
      recommend that clinical decisions about the treatment of such babies be
      individualized and consider many different factors. Nevertheless, many policies
      and practices throughout Europe and North America still appear to base decisions
      on gestational age alone or on gestational age as the primary factor that
      determines whether doctors recommend or even offer life-sustaining neonatal
      intensive care treatment. These policies are well intentioned. They aim to guide
      doctors and parents to make decisions that are best for the baby. That is an
      ethically appropriate goal. But in relying so heavily on gestational age, such
      policies may actually do the babies a disservice by denying some babies treatment
      that might be beneficial and lead to intact survival. In this paper, we argue
      that such policies are unjust to premature babies and ought to be abolished. In
      their place, we propose individualized treatment decisions for premature babies.
      This would treat premature babies as we treat all other patients, with clinical
      decisions based on an individualized estimation of likelihood that treatment
      would be beneficial.

PMID- 29369375
TI  - Safety and efficacy of second-generation drug-eluting stents compared with bare
      metal stents: An updated meta-analysis and regression of 9 randomized clinical
      trials.
AB  - The efficacy of second-generation drug-eluting stents (DES; eg, everolimus and
      zotarolimus) compared with bare-metal stents (BMS) in patients undergoing
      percutaneous coronary intervention was challenged recently by new evidence from
      large clinical trials. Thus, we aimed to conduct an updated systematic review and
      meta-analysis of randomized clinical trials (RCTs) evaluating the efficacy and
      safety of second-generation DES compared with BMS. Electronic databases were
      systematically searched for all RCTs comparing second-generation DES with BMS and
      reporting clinical outcomes. The primary efficacy outcome was major adverse
      cardiac events (MACE); the primary safety outcome was definite stent thrombosis.
      The DerSimonian and Laird method was used for estimation of summary risk ratios
      (RR). A total of 9 trials involving 17 682 patients were included in the final
      analysis. Compared with BMS, second-generation DES were associated with decreased
      incidence of MACE (RR: 0.78, 95% confidence interval [CI]: 0.69-0.88), driven by
      the decreased incidence of myocardial infarction (MI) (RR: 0.67, 95% CI: 0.48
      0.95), target-lesion revascularization (RR: 0.47, 95% CI: 0.42-0.53), definite
      stent thrombosis (RR: 0.57, 95% CI: 0.41-0.78), and definite/probable stent
      thrombosis (RR: 0.54, 95% CI: 0.38-0.80). The incidence of all-cause mortality
      was similar between groups (RR: 0.94, 95% CI: 0.79-1.10). Meta-regression showed
      lower incidences of MI with DES implantation in elderly and diabetic patients (P
      = 0.026 and P < 0.0001, respectively). Compared with BMS, second-generation DES
      appear to be associated with a lower incidence of MACE, mainly driven by lower
      rates of target-lesion revascularization, MI, and stent thrombosis. However, all
      cause mortality appears similar between groups.

PMID- 29369376
TI  - Influencing relatives to respect donor autonomy: Should we nudge families to
      consent to organ donation?
AB  - Refusing consent to organ donation remains unacceptably high, and improving
      consent rates from family or next-of-kin is an important step to procuring more
      organs for solid organ transplantation in countries where this approval is
      sought. We have thus far failed to translate fully our limited understanding of
      why families refuse permission into successful strategies targeting consent in
      the setting of deceased organ donation, primarily because our interventions fail
      to target underlying cognitive obstacles. Novel interventions to overcome these
      hurdles, incorporating an understanding of cognitive psychology and behavioral
      change therapy, may be beneficial. One potential intervention is to use the
      concept of nudge theory, where decision-making is influenced by encouraging
      positive reinforcement and indirect suggestion. Purposefully nudging families to
      given consent for organ donation by understanding, and then overcoming, their
      inherent cognitive biases is novel but also controversial. This article explores
      the roles of relatives in decisions about organ donation, how nudge theory
      translates to organ donation and discusses the arguments for and against its
      application.

PMID- 29369377
TI  - Relational autonomy, care, and Jehovah's Witnesses in Germany.
AB  - Drawing from an ethics of care, relational approaches to autonomy have recently
      emerged in bioethics. Unlike individual autonomy with its emphasis on patients'
      rights, choice, and self-determination which has been the hallmark of bioethics
      consistent with the ideology of individualism in neoliberal democracies in
      Western countries, relational autonomy highlights the relatedness,
      interdependency, and social embeddedness of patients. By examining the mediating
      role that male Hospital Liaison Committee members in Germany play in facilitating
      care that supports Jehovah's Witnesses' refusal of blood transfusions, this
      article moves beyond 'dyadic relations' and contexts of caregiving. It also
      contributes to a deeper understanding of care and relational conceptualizations
      of Witness patients' autonomy globally.

PMID- 29369378
TI  - Heat transfer analysis and resolution quantification of active dynamic
      thermography through human skin.
AB  - OBJECTIVES: Active dynamic thermography (ADT) is a non-contact imaging technique
      that characterizes non-homogeneities in thermal conductance through objects as a
      response to applied energy stimulus. The aim of this study was to (i) develop a
      heat transfer model to define the relationship between thermal stimulation and
      resolution and (ii) empirically quantify the resolution an ADT imaging system can
      detect through a range of depths of human skin. MATERIALS AND METHODS: A heat
      transfer model was developed to describe a thermally non-conductive object below
      a sheet of skin. The size and depth of the object were varied to simulate wound
      conditions, while the intensity and duration of thermal stimulation were varied
      to define stimulation parameters. The model was solved by numerical analysis. For
      ex vivo experimentation, freshly excised human pannus tissue was cut into sheets
      of thickness 2.54-6.35 * 10-4  m (0.010-0.025vinches) for a total of 48 grafts
      from 12 patients. Grafts were placed over a 3D printed resolution target with
      objects ranging from 0.445-0.125 LP/mm. Stimulation from a 300 W halogen lamp
      array was applied for 0.5-14 seconds for a total of 480 experiments. RESULTS: ADT
      resolved a peak of 0.428 +/- 0.025 LP/mm for 2.54 * 10-4  m (0.010 inches) skin
      thickness, 0.384 +/- 0.030 LP/mm for 3.81 * 10-4  m (0.015 inches), 0.325 +/-
      0.042 LP/mm for 5.08 * 10-4  m (0.020 inches) and 0.249 +/- 0.057 LP/mm for 6.35
      * 10-4  m (0.025 inches) skin thickness. Additionally, it was determined that the
      ideal duration of stimulation energy with a 300 W stimulation system was 4
      seconds for 2.54 * 10-4  m, 6 seconds for 3.81 * 10-4  m, 8 seconds for 5.08 * 10
      4  m, and 14 seconds for 6.35 * 10-4  m skin thickness. CONCLUSIONS: This study
      has characterized the correlation between thermal stimulus input and resolvable
      object size and depth for ADT. Through ex vivo experimentation it has also
      quantified the functional imaging depth to below the sub-cutis, beyond that of
      conventional imaging techniques. Lasers Surg. Med. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29369379
TI  - Melanoma in the shopping mall: A utilitarian argument for offering unsolicited
      medical opinions in informal settings.
AB  - Doctors occasionally make diagnoses in strangers outside of formal medical
      settings by using the medical skill of visual inspection, such as noticing signs
      of melanoma or the symptoms of hyperthyroidism. This may cause considerable moral
      unease and doubts on the side of the diagnosing physician. Such encounters force
      physicians to consider whether or not to intervene by introducing themselves to
      the stranger and offering an unsolicited medical opinion despite the absence of a
      formal doctor-patient relationship. A small body of literature has addressed the
      topic of the unsolicited medical opinion, often with a primary focus on practical
      advice. This article seeks to establish an ethical-theoretical basis for
      physicians' ethical obligation to offer an unsolicited medical opinion when they
      make a diagnosis by visual inspection in a stranger outside of the formal medical
      context. Using a utilitarian approach, it is argued that, if it is in the
      physicians' power to prevent a possible loss of well-being, without thereby
      sacrificing anything of equal value, physicians have an ethical obligation to
      intervene.

PMID- 29369380
TI  - Mothers' informational needs when deciding to have their newborn infant
      vaccinated with BCG. A Mixed-methods design.
AB  - OBJECTIVE: To explore the informational needs of mothers with different levels of
      education in order to improve counselling about vaccination. METHODS: In the
      setting of a large vaccination trial, mothers' assessments and yield of written
      information in combination with telephone consultations were evaluated in a
      survey. Furthermore, searching strategies for additional information were
      investigated. Mothers' perspectives on informational needs were explored in focus
      group discussions. RESULTS: Out of 2025 mothers, 95% felt well-informed. Of the
      4% not feeling well-informed, there were significantly more mothers with basic
      schooling and nontheoretical education. There was no correlation between
      searching for additional information and feeling well-informed. The telephone
      consultation was found to be very supportive for the decision. CONCLUSION: The
      written information was digestible over time. The telephone consultation ensured
      the mothers' understanding by tailoring and deriving meaning from the information
      to her special needs. Moreover, it helped the mothers gain an overview of risks
      and benefits and inspired confidence. These findings indicate that the telephone
      consultation improved health literacy. PRACTICE IMPLICATIONS: Individual
      counselling about vaccines is required in addition to information about side
      effects and accurate instructions on how to react upon them.

PMID- 29369381
TI  - Why arguments against infanticide remain convincing: A reply to Rasanen.
AB  - In 'Pro-life arguments against infanticide and why they are not convincing' Joona
      Rasanen argues that Christopher Kaczor's objections to Giubilini and Minerva's
      position on infanticide are not persuasive. We argue that Rasanen's criticism is
      largely misplaced, and that he has not engaged with Kaczor's strongest arguments
      against infanticide. We reply to each of Rasanen's criticisms, drawing on the
      full range of Kaczor's arguments, as well as adding some of our own.

PMID- 29369382
TI  - Rituximab in myasthenia gravis: a "to be or not to be" inhibitor of T cell
      function.
AB  - In recent years, rituximab (RTX), a monoclonal antibody that binds the B
      lymphocyte membrane protein CD20, has been increasingly used for the treatment of
      autoimmune diseases, with the rationale of destroying pathogenic B lymphocytes
      and decreasing autoantibody formation. Surprisingly, RTX has also proven
      effective in predominantly T cell-mediated diseases, raising the question whether
      additional mechanisms may play roles in determining the therapeutic response.
      Here, we review the current literature on the effects of RTX in autoimmune
      diseases, with special emphasis on myasthenia gravis (MG). To elicit a complete
      and effective immune response, B and T lymphocytes cooperate in a loop in which
      they affect each other. Disruption of this cross talk has profound effects on the
      immune system. RTX is likely to affect the whole spectrum of B cell function,
      including antigen presentation, cytokine production, and T cell stimulation. In
      addition, as a small subset of T lymphocytes expresses CD20, its direct targeting
      by RTX may contribute to the therapeutic effect. Owing to its distinctive immune
      characteristics, MG proved to be a useful model to investigate the multifaceted
      implications of B cell depletion.

PMID- 29369383
TI  - Effective altruists ought to be allowed to sell their kidneys.
AB  - Effective altruists aim to do the most good that they can do with the resources
      available to them, without causing themselves or their dependents significant
      harm thereby. The argument presented in this paper demonstrates that there are no
      morally relevant dissimilarities between living kidney donation and living kidney
      selling for effective altruistic reasons. Thus, since the former is allowed, the
      latter ought to be allowed as well. And, there are important moral differences
      between living kidney selling for effective altruistic reasons and other reasons
      for kidney vending (e.g., for personal financial gain), such that standard
      objections against markets in human kidneys do not attach to those markets
      designed around principles of effective altruism. The reasonable conclusion to
      draw from this is that eligible effective altruist kidney donors ought to be
      allowed to sell (one of) their kidneys to others in need, if they so desire.
      Because of this, law and policy ought to be changed to allow for this exceptional
      case: current laws that ban kidney selling for everyone, irrespective of their
      reason for selling, are unjustified.

PMID- 29369384
TI  - Ecological causes and consequences of flower color polymorphism in a self
      pollinating plant (Boechera stricta).
AB  - Intraspecific variation in flower color is often attributed to pollinator
      mediated selection, yet this mechanism cannot explain flower color polymorphisms
      in self-pollinating species. Indirect selection mediated via biotic and abiotic
      stresses could maintain flower color variation in these systems. The selfing
      forb, Boechera stricta, typically displays white flowers, but some individuals
      produce purple flowers. We quantified environmental correlates of flower color in
      natural populations. To disentangle plasticity from genotypic variation, we
      performed a multiyear field experiment in five gardens. In controlled conditions,
      we evaluated herbivore preferences and the effects of drought stress and soil pH
      on flower color expression. In natural populations, purple-flowered individuals
      experienced lower foliar herbivory than did their white-flowered counterparts.
      This pattern also held in the common gardens. Additionally, low-elevation
      environments induced pigmented flowers (plasticity), and the likelihood of floral
      pigmentation decreased with source elevation of maternal families (genetic
      cline). Viability selection favored families with pigmented flowers. In the
      laboratory, herbivores exerted greater damage on tissue derived from white- vs
      purple-flowered individuals. Furthermore, drought induced pigmentation in white
      flowered lineages, and white-flowered plants had a fecundity advantage in the
      well-watered control. Flower color variation in selfing species is probably
      maintained by herbivory, drought stress, and other abiotic factors that vary
      spatially.

PMID- 29369385
TI  - Maximization of regional probabilities using Optimal Surface Graphs: Application
      to carotid artery segmentation in MRI.
AB  - PURPOSE: We present a segmentation method that maximizes regional probabilities
      enclosed by coupled surfaces using an Optimal Surface Graph (OSG) cut approach.
      This OSG cut determines the globally optimal solution given a graph constructed
      around an initial surface. While most methods for vessel wall segmentation only
      use edge information, we show that maximizing regional probabilities using an OSG
      improves the segmentation results. We applied this to automatically segment the
      vessel wall of the carotid artery in magnetic resonance images. METHODS: First,
      voxel-wise regional probability maps were obtained using a Support Vector Machine
      classifier trained on local image features. Then, the OSG segments the regions
      which maximizes the regional probabilities considering smoothness and topological
      constraints. RESULTS: The method was evaluated on 49 carotid arteries from 30
      subjects. The proposed method shows good accuracy with a Dice wall overlap of
      74.1 +/- 4.3%, and significantly outperforms a published method based on an OSG
      using only surface information, the obtained segmentations using voxel-wise
      classification alone, and another published artery wall segmentation method based
      on a deformable surface model. Intraclass correlations (ICC) with manually
      measured lumen and wall volumes were similar to those obtained between observers.
      Finally, we show a good reproducibility of the method with ICC = 0.86 between the
      volumes measured in scans repeated within a short time interval. CONCLUSIONS: In
      this work, a new segmentation method that uses both an OSG and regional
      probabilities is presented. The method shows good segmentations of the carotid
      artery in MRI and outperformed another segmentation method that uses OSG and edge
      information and the voxel-wise segmentation using the probability maps.

PMID- 29369386
TI  - Epigenetic Modifications of Cytosine: Biophysical Properties, Regulation, and
      Function in Mammalian DNA.
AB  - To decode the function and molecular recognition of several recently discovered
      cytosine derivatives in the human genome - 5-hydroxymethylcytosine, 5
      formylcytosine, and 5-carboxylcytosine - a detailed understanding of their
      effects on the structural, chemical, and biophysical properties of DNA is
      essential. Here, we review recent literature in this area, with particular
      emphasis on features that have been proposed to enable the specific recognition
      of modified cytosine bases by DNA-binding proteins. These include electronic
      factors, modulation of base-pair stability, flexibility, and radical changes in
      duplex conformation. We explore these proposals and assess whether or not they
      are supported by current biophysical data. This analysis is focused primarily on
      the properties of epigenetically modified DNA itself, which provides a basis for
      discussion of the mechanisms of recognition by different proteins.

PMID- 29369387
TI  - Phenotype and natural history of elderly onset inflammatory bowel disease: a
      multicentre, case-control study.
AB  - BACKGROUND: Onset during old age has been reported in upto 10% of total cases of
      inflammatory bowel disease (IBD). AIM: To evaluate phenotypic characteristics and
      the use of therapeutic resources in patients with elderly onset IBD. METHODS:
      Case-control study including all those patients diagnosed with IBD over the age
      of 60 years since 2000 who were followed-up for >12 months, identified from the
      IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40
      years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult
      onset). RESULTS: One thousand three hundred and seventy-four elderly onset and
      1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's
      disease (CD)). Among UC patients, elderly onset cases had a lower proportion of
      extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an
      increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive
      colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs
      19%; P < 0.0001) was significantly less frequent. Regarding the use of
      therapeutic resources, there was a significantly lower use of corticosteroids (P
      < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in
      elderly onset cases. Regarding surgery, we found a significantly higher surgery
      rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly
      onset cases were characterised by a higher rate of hospitalisations (66% vs 49%;
      P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). CONCLUSIONS: Elderly onset
      IBD shows specific characteristics and they are managed differently, with a lower
      use of immunosuppressants and a higher rate of surgery in UC.

PMID- 29369388
TI  - Targeted metabolomic analysis of 33 amino acids and biogenic amines in human
      urine by ion-pairing HPLC-MS/MS: Biomarkers for tacrolimus nephrotoxicity after
      renal transplantation.
AB  - Calcineurin inhibitor nephrotoxicity, especially for the widely used tacrolimus,
      has become a major concern in post-transplant immunosuppression. Multiparametric
      amino acid metabolomics is useful for biomarker identification of tacrolimus
      nephrotoxicity, for which specific quantitative methods are highlighted as a
      premise. This article presents a targeted metabolomic assay to quantify 33 amino
      acids and biogenic amines in human urine by high-performance liquid
      chromatography coupled with tandem mass spectrometry. Chromatographic separation
      was carried out on an Agilent Zorbax SB-C18 column (3.0 * 150 mm, 5 MUm) with
      addition of an ion-pairing agent in the mobile phase, and MS/MS detection was
      achieved in both the positive and negative multiple reaction monitoring modes.
      Good correlation coefficients (r2 > 0.98) were obtained for most analytes. Intra-
      and inter-day precision, stability, carryover and incurred sample reanalysis met
      with the acceptance criteria of the guidance of the US Food and Drug
      Administration. Analysis on urine from healthy volunteers and renal
      transplantation patients with tacrolimus nephrotoxicity confirmed symmetric
      dimethylarginine and serine as biomarkers for kidney injury, with AUC values of
      0.95 and 0.81 in receiver operating characteristic analysis, respectively.
      Additionally, symmetric dimethylarginine exhibited a tight correlation with serum
      creatinine, and was therefore indicative of renal function. The targeted
      metabolomic assay was time and cost prohibitive for amino acid analysis in human
      urine, facilitating the biomarker identification of tacrolimus nephrotoxicity.

PMID- 29369389
TI  - The future-like-ours argument, animalism, and mereological universalism.
AB  - Which metaphysical theories are involved-whether presupposed or implied-in
      Marquis' future-like-ours (FLO) argument against abortion? Vogelstein has
      recently argued that the supporter of the FLO argument faces a problematic
      dilemma; in particular, Marquis, the main supporter of the argument, seems to
      have to either (a) abandon diachronic universalism (DU) or (b) acquiesce and
      declare that contraception is morally wrong. I argue that the premises of
      Marquis' argument can be reasonably combined with a form of unrestricted
      composition and that the FLO argument is better viewed as including animalism,
      i.e., the thesis that we are animals.

PMID- 29369390
TI  - CDX2 and LEF-1 expression in pilomatrical tumors and their utility in the
      diagnosis of pilomatrical carcinoma.
AB  - BACKGROUND: The Wnt signaling pathway has been implicated in the pathogenesis of
      pilomatrical tumors. Lymphoid enhancer-binding factor 1 (LEF-1) is a downstream
      component of this pathway, and Caudal-related homeobox transcription factor 2
      (CDX2) has been postulated to regulate it, but little is known about expression
      of these transcription factors in pilomatrical tumors. METHODS:
      Immunohistochemistry for CDX2, beta-catenin, LEF-1, CK19, CK5, Special AT-rich
      sequence- binding protein 2 (SATB2), cadherin 17 and androgen receptor was
      performed on pilomatricomas (PMs) (N = 12), pilomatrical carcinomas (PMCAs) (N =
      12) and non-pilomatrical cutaneous tumors (N = 18). RESULTS: PMs and PMCAs were
      positive for CDX2 (9/12 PMs, sensitivity = 75%, specificity = 100%; 11/12 PMCAs,
      sensitivity = 92%, specificity = 100%; P < 0.01), beta-catenin (12/12 PMs,
      sensitivity = 100%, specificity = 94%; 10/12 PMCAs, sensitivity = 83%,
      specificity = 94%; P < 0.01) and LEF-1 (12/12 PMs, sensitivity = 100%,
      specificity = 56%; 12/12 PMCAs, sensitivity = 100%, specificity = 56%; P < 0.01).
      CDX2 expression was commonly focal, within a discrete subpopulation of squamoid
      cells. The LEF-1 expression pattern was different and discernable between
      pilomatrical tumors (strong, diffuse) and non-pilomatrical tumors (weak, patchy).
      CONCLUSION: This study reaffirms the importance of the Wnt signaling pathway in
      the tumorigenesis of pilomatrical tumors, and this introduces CDX2 as a possible
      regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at
      least as well as beta-catenin, if not better when taking into account expression
      pattern, as a diagnostic marker for PMCA, and should be considered in the workup
      of ambiguous primitive-appearing cutaneous tumors.

PMID- 29369391
TI  - Review: Somatic mutations in neurodegeneration.
AB  - Somatic mutations are postzygotic mutations which may lead to mosaicism, the
      presence of cells with genetic differences in an organism. Their role in cancer
      is well established, but detailed investigation in health and other diseases has
      only been recently possible. This has been empowered by the improvements of
      sequencing techniques, including single-cell sequencing, which can still be error
      prone but is rapidly improving. Mosaicism appears relatively common in the human
      body, including the normal brain, probably arising in early development, but also
      potentially during ageing. In this review, we first discuss theoretical
      considerations and current evidence relevant to somatic mutations in the brain.
      We present a framework to explain how they may be integrated with current views
      on neurodegeneration, focusing mainly on sporadic late-onset neurodegenerative
      diseases (Parkinson's disease, Alzheimer's disease and amyotrophic lateral
      sclerosis). We review the relevant studies so far, with the first evidence
      emerging in Alzheimer's in particular. We also discuss the role of mosaicism in
      inherited neurodegenerative disorders, particularly somatic instability of tandem
      repeats. We summarize existing views and data to present a model whereby the time
      of origin and spatial distribution of relevant somatic mutations, combined with
      any additional risk factors, may partly determine the development and onset age
      of sporadic neurodegenerative diseases.

PMID- 29369392
TI  - Cutaneous intravascular CD30+ T-cell pseudolymphoma occurring in a regressing
      keratoacanthoma.
AB  - Cutaneous intravascular CD30+ pseudolymphoma is an uncommon incidental finding
      that may mimic intravascular or angiotropic lymphoma. We describe a 78-year-old
      female with a traumatized regressing keratoacanthoma on her left cheek. A shave
      biopsy revealed intravascular staining of atypical lymphocytes positive for CD45,
      CD3 and CD30. Clinical exam revealed no other evidence of lymphoma, the patient
      denied constitutional symptoms, and routine blood work was normal. The patient is
      healthy and doing well 28 months after her first visit. CD30+ pseudolymphoma
      should be distinguished from malignant intravascular lymphoproliferative
      disorders.

PMID- 29369393
TI  - Case of psoriatic arthritis mutilans whose finger dysfunction was successfully
      ameliorated by surgical intervention during infliximab treatment.

PMID- 29369395
TI  - Case with anaphylactic shock induced by heparin-lock flush injection.

PMID- 29369396
TI  - Current developments in phototherapy for psoriasis.
AB  - Phototherapy utilizes the beneficial effects of ultraviolet (UV) wavelengths to
      affect immunoregulatory functions. UV light phototherapy using narrowband UV-B
      (NB-UVB) and bath-psoralen UV-A (bath-PUVA) therapy are well-established
      treatments for psoriasis. Dual-action mechanisms of UV phototherapy have been
      identified: apoptosis and immune suppression. NB-UVB depletes pathogenic T cells
      by inducing apoptosis and regulatory T cells. Other wavelengths are also utilized
      for phototherapy, namely 308-nm excimer light and 312-nm flat-typed NB-UVB.
      Excimer light (308-nm) therapy effectively targets the affected skin without
      unduly exposing other areas and increases the levels of regulatory T cells.
      Phototherapy improves impaired resting regulatory T cells and increases activated
      regulatory T cells in patients with psoriasis. Intensive studies of phototherapy
      effects have led to several improvements in the design, protocols, and light
      sources, such as UV light-emitting diodes, thereby providing several options for
      patients with refractory skin disease, such as psoriasis.

PMID- 29369397
TI  - Metallothioneins are neuroprotective agents in lysosomal storage disorders.
AB  - OBJECTIVE: Lysosomal storage disorders (LSDs) are a broad class of inherited
      metabolic diseases caused by the defective activity of lysosomal enzymes. Central
      nervous system (CNS) manifestations are present in roughly 50% of LSD patients
      and represent an unmet medical need for them. We explored the therapeutic
      potential of metallothioneins (MTs), a newly identified family of proteins with
      reported neuroprotective roles, in the murine models of two LSDs with CNS
      involvement. METHODS: MT-1 overexpressing transgenic mice (MTtg) were crossed
      with the murine models of Batten and Krabbe diseases. Changes in the survival and
      manifestations of the disease in the MTtg setting were assessed. In addition, we
      analyzed the therapeutic effects of MT-1 CNS gene delivery in one of these LSD
      models. RESULTS: Constitutive expression of MT-1 exerted favorable phenotypic
      effects in both LSD models. MT-LSD mice showed a 5% to 10% increase in survival
      and slower disease progression as compared to not-transgenic LSD mice. Rescue of
      Purkinje cells from degeneration and apoptosis was also observed in the MT-LSD
      models. This phenotypic amelioration was accompanied by a modulation of the
      disease-associated activated inflammatory microglia phenotype, and by a reduction
      of oxidative stress. Importantly, for the clinical translation of our findings,
      the very same effects were obtained when MTs were delivered to brains by systemic
      AAV gene transfer. INTERPRETATION: MTs can be considered novel therapeutic agents
      (and targets) in LSDs and potentiate the effects of approaches aiming at
      correction of the disease-causing enzyme deficiency in the CNS. Ann Neurol
      2018;83:418-432 Ann Neurol 2018;83:418-432.

PMID- 29369398
TI  - Neutrophil hyperactivation correlates with Alzheimer's disease progression.
AB  - OBJECTIVE: Recent studies have underlined the effect of systemic inflammation on
      the pathophysiology of Alzheimer's disease (AD). Neutrophils are key components
      of early innate immunity and contribute to uncontrolled systemic inflammation if
      not tightly regulated. The aim of our study was to fully characterize human
      circulating neutrophils at different disease stages in AD. METHODS: We analyzed
      neutrophil phenotypes and functions in 42 patients with AD (16 with mild
      cognitive impairment and 26 with dementia), and compared them to 22 age-matched
      healthy subjects. This study was performed directly in whole blood to avoid
      issues with data interpretation related to cell isolation procedures. RESULTS:
      Blood samples from AD patients with dementia revealed neutrophil hyperactivation
      associated with increased reactive oxygen species production and increased levels
      of intravascular neutrophil extravascular traps. The homeostasis of circulating
      neutrophils in these patients also changed: The ratio between the harmful
      hyperreactive CXCR4high /CD62Llow senescent and the CD16bright /CD62Ldim
      immunosuppressive neutrophil subsets rose in the later stage of the disease.
      These abnormalities were greater in fast-decliner than in slow-decliner patients.
      INTERPRETATION: Our results indicate that the inflammatory properties of
      circulating neutrophils shift as the percentage of aged neutrophils expands in
      patients with AD-changes that may play an instrumental role in establishing
      systemic chronic inflammation. Most important, our data strongly suggest that the
      neutrophil phenotype may be associated with the rate of cognitive decline and may
      thus constitute an innovative and prognostic blood biomarker in patients with AD.
      Ann Neurol 2018;83:387-405.

PMID- 29369400
TI  - Lichen planopilaris and frontal fibrosing alopecia cannot be differentiated by
      histopathology.
AB  - BACKGROUND: Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA)
      represent 2 entities that cause primary cicatricial alopecia. These entities are
      clinically different; nevertheless, the literature suggests that FFA represents a
      form of LPP. The main argument in support of this hypothesis is that previous
      studies comparing the histologic findings have not found obvious differences
      between these diseases. METHODS: Our objective was to more critically compare and
      contrast 20 histologic findings of these diseases in a large number of patients
      in order to determine any significant histologic differences between LPP and FFA.
      RESULTS: We found 3 parameters that were statistically different, namely the
      presence of terminal catagen-telogen hairs (50% FFA vs 23.5% LPP; P = .020); a
      severe perifollicular inflammatory infiltrate (29.4% LPP vs 4.6% FFA; P = .010)
      and a zone of concentric lamellar fibroplasia (85.3% LPP vs 63.6% FFA; P = .041).
      CONCLUSIONS: Although a few histologic features differ between FFA and LPP, we
      believe that these differences are too subtle or non-specific to distinguish
      between them with confidence. Therefore, clinical correlation is essential to
      establish the diagnosis.

PMID- 29369399
TI  - Expression profiling suggests microglial impairment in human immunodeficiency
      virus neuropathogenesis.
AB  - OBJECTIVE: CD16+ /CD163+ macrophages (MPhis) and microglia accumulate in the
      brains of patients with human immunodeficiency virus (HIV) encephalitis (HIVE), a
      neuropathological correlate of the most severe form of HIV-associated
      neurocognitive disorders, HIV-associated dementia. Recently, we found that some
      parenchymal microglia in brain of HIV+ subjects without encephalitis (HIV/noE)
      but with varying degrees of neurocognitive impairment express CD16 and CD163,
      even in the absence of detectable virus production. To further our understanding
      of microglial activation in HIV, we investigated expression of specific genes by
      profiling parenchymal microglia from archival brain tissue of patients with HIVE
      and HIV/noE, and HIV- controls. METHODS: Single-population microarray analyses
      were performed on ~2,500 laser capture microdissected CD163+ , CD16+ , or CD68+
      MPhis/microglia per case, using terminal continuation RNA amplification and a
      custom-designed array platform. RESULTS: Several classes of microglial
      transcripts in HIVE and HIV/noE were altered, relative to HIV- subjects,
      including factors related to cell stress, immune activation, and apoptosis.
      Additionally, several neurotrophic factors were reduced in HIV infection,
      suggesting an additional mechanism of neuropathogenesis. The majority of
      transcripts altered in HIVE displayed intermediate changes in HIV/noE.
      INTERPRETATION: Our results support the notion that microglia contribute to the
      maintenance of brain homeostasis and their potential loss of function in the
      context of chronic inflammation contributes to neuropathogenesis. Furthermore,
      they indicate the utility of profiling MPhis/microglia to increase our
      understanding of microglia function, as well as to ascertain alterations in
      specific pathways, genes, and potentially, encoded proteins that may be amenable
      to targeted treatment modalities in diseases affecting the brain. Ann Neurol
      2018;83:406-417.

PMID- 29369401
TI  - Pallidal deep brain stimulation modulates cortical excitability and plasticity.
AB  - OBJECTIVE: Internal globus pallidus (GPi) deep brain stimulation (DBS) relieves
      symptoms in dystonia patients. However, the physiological effects produced by GPi
      DBS are not fully understood. In particular, how a single-pulse GPi DBS changes
      cortical circuits has never been investigated. We studied the modulation of motor
      cortical excitability and plasticity with single-pulse GPi DBS in dystonia
      patients with bilateral implantation of GPi DBS. METHODS: The cortical evoked
      potentials from DBS were recorded with electroencephalography. Transcranial
      magnetic stimulation with a conditioning test paired-pulse paradigm was used to
      investigate the effect of GPi DBS on the primary motor cortex. How GPi DBS might
      modulate the motor cortical plasticity was tested using a paired associative
      stimulation paradigm with repetitive pairs of GPi DBS and motor cortical
      stimulation at specific time intervals. RESULTS: GPi stimulation produced 2 peaks
      of cortical evoked potentials with latencies of ~10 and ~25 milliseconds in the
      motor cortical area. Cortical facilitation was observed at ~10 milliseconds after
      single-pulse GPi DBS, and cortical inhibition was observed after a ~25
      millisecond interval. Repetitive pairs of GPi stimulation with cortical
      stimulation at these 2 time intervals produced long-term potentiation-like
      effects in the motor cortex. INTERPRETATION: Single-pulse DBS modulates cortical
      excitability and plasticity at specific time intervals. These effects may be
      related to the mechanism of action of DBS. Combination of DBS with cortical
      stimulation with appropriate timing has therapeutic potential and could be
      explored in the future as a method to enhance the effects of neuromodulation for
      neurological and psychiatric diseases. Ann Neurol 2018;83:352-362.

PMID- 29369402
TI  - Impact of a new simplified disability scoring system for adult patients with
      localized scleroderma.
AB  - Localized scleroderma (LoS) involves dermal but not internal inflammation and
      fibrosis. Cosmetic changes often impact quality of life (QOL), however,
      impairment of activities of daily living (ADL) in LoS patients has not been
      investigated. To determine what factor(s) are associated with ADL in adult
      patients with LoS, we performed a retrospective observational study in 177
      Japanese adult LoS patients using a novel LoS disability score based on Barthel's
      indices of ADL: feeding, bathing, grooming, dressing, bowels, bladder, toilet
      use, transfers, mobility and stairs. LoS disability scores increased in
      proportion to the number of affected body parts but were not correlated to age
      and duration of illness. The presence of leg lesions significantly impaired ADL
      of LoS patients compared with lesions on other body parts. Patients treated with
      systemic medications, who tended to have multiple lesions, presented higher LoS
      disability scores than those without systemic treatments. Our study proposes that
      physicians evaluate ADL, not only QOL, in LoS patients. Our findings using LoS
      disability scoring indicate that multiple affected body parts and leg lesions are
      risk factors for ADL impairment.

PMID- 29369403
TI  - #dermpathJC: The first online dermatopathology Twitter journal club.

PMID- 29369404
TI  - A novel mutation in the transmembrane 6 domain of GABBR2 leads to a Rett-like
      phenotype.

PMID- 29369405
TI  - Targeting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in
      metastatic melanoma to increase efficacy of BRAFV600E inhibitors.
AB  - Melanoma is one of the deadliest forms of skin cancer. Although BRAF inhibitors
      significantly enhance survival of metastatic melanoma patients, most patients
      relapse after less than a year of treatment. We previously reported that mRNA
      binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is
      overexpressed in metastatic melanoma and that expression of IGF2BP1 confers
      resistance to chemotherapeutic agents. Here we demonstrate that IGF2BP1 plays an
      important role in the sensitivity of melanoma to targeted therapy. Inhibition of
      IGF2BP1 enhances the effects of BRAF-inhibitor and BRAF-MEK inhibitors in
      BRAFV600E melanoma. Also, knockdown of IGF2BP1 alone is sufficient to reduce
      tumorigenic characteristics in vemurafenib-resistant melanoma. These findings
      suggest that IGF2BP1 can be a novel therapeutic target for melanoma.

PMID- 29369406
TI  - Effect of increased mechanical knee joint loading during running on the serum
      concentration of cartilage oligomeric matrix protein (COMP).
AB  - The purpose of the study was to investigate the effect of an increase in
      mechanical knee joint loading during running on the serum COMP level. On two
      different test days, 20 healthy men ran with knee orthoses for 30 min on a
      treadmill (v = 2.2 m/s). On day 1, the orthoses were passive, whereas on day 2
      they were pneumatically driven (active) and thus increased the external knee
      flexion moments (+30.9 Nm) during stance phase. Lower-limb mechanics and serum
      COMP levels (baseline; 0, 0.5, 1, 2 h post running) were analyzed. COMP levels
      increased immediately after running with passive (+35%; pre: 7.5 U/l, 95%CI: 6.4,
      8.7, post: 9.8 U/l, 95%CI: 8.8, 10.8, p < 0.001) and active orthoses (+45%; pre:
      7.6 U/l; 95%CI: 6.4, 8.8, post: 10.3 U/l, 95%CI: 9.2, 11.5, p < 0.001), but they
      did not differ between interventions. While running with active orthoses, greater
      ankle dorsiflexion angles, knee flexion angles, and moments occurred (p < 0.05).
      Comparing both interventions, the Delta COMP pre-post, meaning the difference
      (Delta) between running with active and passive orthoses in pre to post COMP
      level change (=level after (post) running minus level before (pre) running),
      correlated negatively with Delta COMP baseline (difference between the baseline
      COMP level before running with active and passive orthoses, r = -0.616; p =
      0.004), and with a positive tendence with the Delta maximum knee flexion (r =
      0.388; p = 0.091). Therefore, changes in COMP concentration after physical
      activity seem to be highly influenced by the COMP baseline level. In addition,
      correlation analysis indicates that modifications in knee joint kinematics have a
      greater effect on cartilage metabolism than an increase in joint moments. (c)
      2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop
      Res 36:1937-1946, 2018.

PMID- 29369408
TI  - Exploring the functional impact of mutational drift in LRRK2 gene and
      identification of specific inhibitors for the treatment of Parkinson disease.
AB  - Parkinson's disease (PD) is a disorder of the central nervous system that is
      caused due to the death of the dopaminergic neurons in the region of the brain
      called substantia nigra. Mutations in LRRK2 genes are associated with disease
      condition and it's been reported as crucial factor for drug resistance.
      Identification of deleterious mutations and studying the structural and
      functional impact of such mutations may lead to the identification of potential
      selective inhibitors. In this study, we analyzed 52 PD associated mutations,
      among that 20 were identified as highly deleterious. The deleterious mutations
      G2019S and I2020T in the kinase domain were playing a key role in causing
      resistance to drug levedopa. Molecular docking analyses have been performed to
      understand the binding affinity of levodapa with LRRK2 in wild and mutant
      condition. Molecular docking results show that levedopa binds differentially and
      obtained less number of hydrogen bonds in compared with wild type LRRK2. In
      addition, molecular dynamics simulations were performed to study the efficacy of
      docked complexes and it was observed that the efficacy of the mutant complexes
      (G2019S-Levodopa and I2020T-Levodopa) affected in the presence of mutation.
      Finally, through virtual screening approach specific inhibitors SCHEMBL6473053
      and SCHEMBL1278779 have been identified that could potentially inhibit LLRK2
      mutants G2019S and I2020T respectively. Over all this computational investigation
      correlates the impact of genotypic modulation in structure and function of drug
      target which enhanced in the identification of precision medicine to treat PD.

PMID- 29369407
TI  - Characterization of D-maltose as a T2 -exchange contrast agent for dynamic
      contrast-enhanced MRI.
AB  - PURPOSE: We sought to investigate the potential of D-maltose, D-sorbitol, and D
      mannitol as T2 exchange magnetic resonance imaging (MRI) contrast agents. We also
      sought to compare the in vivo pharmacokinetics of D-maltose with D-glucose with
      dynamic contrast enhancement (DCE) MRI. METHODS: T1 and T2 relaxation time
      constants of the saccharides were measured using eight pH values and nine
      concentrations. The effect of echo spacing in a multiecho acquisition sequence
      used for the T2 measurement was evaluated for all samples. Finally, performances
      of D-maltose and D-glucose during T2 -weighted DCE-MRI were compared in vivo.
      RESULTS: Estimated T2 relaxivities (r2 ) of D-glucose and D-maltose were highly
      and nonlinearly dependent on pH and echo spacing, reaching their maximum at pH =
      7.0 (~0.08 mM-1 s-1 ). The r2 values of D-sorbitol and D-mannitol were estimated
      to be ~0.02 mM-1 s-1 and were invariant to pH and echo spacing for pH <=7.0. The
      change in T2 in tumor and muscle tissues remained constant after administration
      of D-maltose, whereas the change in T2 decreased in tumor and muscle after
      administration of D-glucose. Therefore, D-maltose has a longer time window for T2
      -weighted DCE-MRI in tumors. CONCLUSION: We have demonstrated that D-maltose can
      be used as a T2 exchange MRI contrast agent. The larger, sustained T2 -weighted
      contrast from D-maltose relative to D-glucose has practical advantages for tumor
      diagnoses during T2 -weighted DCE-MRI. Magn Reson Med 80:1158-1164, 2018. (c)
      2018 International Society for Magnetic Resonance in Medicine.

PMID- 29369409
TI  - Parkinson disease and the risk of epileptic seizures.
AB  - OBJECTIVE: To assess the association between incident Parkinson disease (PD) and
      subsequent incident epileptic seizures. METHODS: We conducted a retrospective
      cohort study with a nested case-control analysis using data from the U.K.
      Clinical Practice Research Datalink. We identified patients aged >=40 years with
      an incident diagnosis of PD between 1995 and 2016 and a matched comparison group
      of PD-free individuals. We calculated crude incidence rates (IRs) with 95%
      confidence intervals (CIs) of epileptic seizures in PD patients and the PD-free
      comparison group, and corresponding crude incidence rate ratios (IRRs). In the
      nested case-control analysis, we calculated adjusted odds ratios (adj. ORs) of
      incident PD among cases with incident epileptic seizures and seizure-free
      controls overall and stratified by various seizure-provoking comorbidities.
      RESULTS: Among 23,086 incident PD patients and 92,343 PD-free individuals, we
      identified 898 patients with incident epileptic seizures. The crude IR of
      epileptic seizures in PD patients was 266.7/100,000 person-years (95% CI = 235.6
      297.7), and in PD-free individuals it was 112.4/100,000 person-years (95% CI =
      103.5-121.3; IRR = 2.37, 95% CI = 2.06-2.73). The adj. OR of epileptic seizures
      was 1.68 (95% CI = 1.43-1.98) in PD patients compared with PD-free individuals.
      PD patients with comorbid brain disorders (adj. OR = 12.36, 95% CI = 8.74-17.48)
      or with > 1 seizure-provoking comorbidity (adj. OR = 13.24, 95% CI = 10.15-17.25)
      were at the highest risk of epileptic seizures compared with PD-free individuals
      with no seizure-provoking comorbidities. INTERPRETATION: This study suggests that
      incident PD is associated with an increased risk of incident epileptic seizures.
      Ann Neurol 2018;83:363-374.

PMID- 29369410
TI  - Protective effects of microRNA-330 on amyloid beta-protein production, oxidative
      stress, and mitochondrial dysfunction in Alzheimer's disease by targeting VAV1
      via the MAPK signaling pathway.
AB  - This study aims to explore the effect of miR-330 targeting VAV1 on amyloid beta
      protein (Abeta) production, oxidative stress (OS), and mitochondrial dysfunction
      in Alzheimer's disease (AD) mice through the MAPK signaling pathway. Putative
      targeted gene of miR-330 was performed by a miRNA target prediction website and
      dual-luciferase reporter gene assay. AD mouse model was successfully established.
      Fourteen C57 mice were randomized into AD and control groups. The positive
      protein expression rate of VAV1 was measured by immunohistochemistry. Neuron
      cells were assigned into control, blank, negative control (NC), miR-330 mimics,
      miR-330 inhibitors, siRNA-VAV1, and miR-330 inhibitors + siRNA-VAV1 groups.
      Expression of miR-330, VAV1, ERK1, JNK1, P38MAPK, Abeta, COX, and lipoprotein
      receptor-related protein-1 (LRP-1) were determined using RT-qPCR and Western
      blotting. Colorimetry was applied to measure the levels of OS parameters of
      superoxide dismutase (SOD) and malondialdehyde (MDA). Abeta production in brain
      tissue was detected using ELISA, while that in neuron cell was measured by
      radioimmunoassay. MiR-330 was down-regulated in neuron cells of AD mice and VAV1
      was negatively regulated by miR-330. Compared with the control group, the
      positive protein expression rate of VAV1 was significantly elevated in the AD
      group. Overexpression of miR-330 decreased the expression of VAV1, ERK1, JNK1,
      P38MAPK, and Abeta, but increased the expression of COX and LRP-1. AD mice
      revealed elevated Abeta production and MDA with decreased SOD level. The result
      indicates that overexpressed miR-330 targeting VAV1 through the MAPK signaling
      pathway reduces Abeta production and alleviates OS and mitochondrial dysfunction
      in AD.

PMID- 29369411
TI  - Safety and efficacy of epicutaneous immunotherapy for food allergy.
AB  - Food allergy is increasingly common in children, affecting about 4%-8%. The
      mainstays of management remain allergen avoidance and emergency preparedness to
      treat allergic reactions with emergency medications. Unfortunately, these
      approaches are unsatisfactory for many patients and their families as the
      restrictions, constant vigilance, and unpredictable severity of allergic
      reactions negatively impact quality of life. In recent decades, there has been
      significant interest in developing treatments for food allergy that lead to
      desensitization to increase thresholds for triggering allergic reactions and
      decrease the risk of reacting to allergen-contaminated food products.
      Epicutaneous immunotherapy (EPIT) is a novel therapy that is currently under
      investigation, delivering allergen via repeated applications to the skin and
      targeting antigen-presenting cells in the superficial skin layers. Murine models
      have demonstrated that allergen uptake is an active process by skin dendritic
      cells with subsequent migration to draining lymph nodes. Allergen exposure to the
      non-vascularized epidermis limits systemic absorption, contributing to the high
      safety profile. Results from murine experiments showed that EPIT has comparable
      efficacy as subcutaneous immunotherapy in terms of challenge outcomes, airway
      hyper-responsiveness, and immunologic parameters. Several clinical trials of EPIT
      have recently been completed or are ongoing. Results support the high safety and
      tolerability of this approach. Efficacy data suggest that the change in threshold
      eliciting dose following 1 year of therapy is less than that seen compared to
      high-dose (2-4 g peanut protein) oral immunotherapy, but more prolonged treatment
      with EPIT appears to lead to increasing desensitization. Additional data from
      larger-scale studies should provide a more robust assessment of safety and
      efficacy of EPIT.

PMID- 29369412
TI  - Dilution destabilizes engineered ligand-coated nanoparticles in aqueous
      suspensions.
AB  - It is commonly true that a diluted colloidal suspension is more stable over time
      than a concentrated one because dilution reduces collision rates of the particles
      and therefore delays the formation of aggregates. However, this generalization
      does not apply for some engineered ligand-coated nanoparticles (NPs). We observed
      the opposite relationship between stability and concentration of NPs. We tested 4
      different types of NPs: CdSe-11-mercaptoundecanoic acid, CdTe-polyelectrolytes,
      Ag-citrate, and Ag-polyvinylpyrrolidone. The results showed that dilution alone
      induced aggregation and subsequent sedimentation of the NPs that were originally
      monodispersed at very high concentrations. Increased dilution caused NPs to
      progressively become unstable in the suspensions. The extent of the dilution
      impact on the stability of NPs is different for different types of NPs. We
      hypothesize that the unavoidable decrease in free ligand concentration in the
      aqueous phase following dilution causes detachment of ligands from the suspended
      NP cores. The ligands attached to NP core surfaces must generally approach
      exchange equilibrium with free ligands in the aqueous phase; therefore, ligand
      detachment and destabilization are expected consequences of dilution. More
      studies are necessary to test this hypothesis. Because the stability of NPs
      determines their physicochemical and kinetic behavior including toxicity,
      dilution-induced instability needs to be understood to realistically predict the
      behavior of engineered ligand-coated NPs in aqueous systems. Environ Toxicol Chem
      2018;37:1301-1308. (c) 2018 SETAC.

PMID- 29369413
TI  - Comments on Schocker et al.

PMID- 29369414
TI  - Molecular sensitization patterns and influence of molecular diagnosis in
      immunotherapy prescription in children sensitized to both grass and olive pollen.
AB  - BACKGROUND: The overlapping grass and olive pollen seasons in Spain and the
      phenomenon of cross-reactivity can make it difficult to determine the true
      causative agent of seasonal allergic rhinitis when only skin prick tests with
      whole extracts are used. The aim of the GRAMOLE study was to determine
      sensitization patterns to the major grass and olive pollen allergens detected
      using specific recombinant IgE and to explore how this knowledge affected
      physicians' choice of allergen-specific immunotherapy. METHODS: Epidemiological,
      observational, multicenter, cross-sectional study. Results from children under 18
      years of age diagnosed with seasonal allergic rhinitis by positive skin prick
      tests to olive and grass pollen were analyzed. Specific IgE to Phl p 1+5, Ole e
      1, and Phl p 7+12 was determined. Investigators specified the optimal composition
      of allergen immunotherapy before and after knowing the results of the molecular
      diagnosis. RESULTS: A total of 281 patients with a mean age of 13.4 years were
      included. Double sensitization to both major allergens was found in vitro in 76%
      of children for an IgE cutoff point of 0.35 kU/L. When the molecular diagnosis
      results were known, specialists changed the composition of the prescribed
      immunotherapy in 52.87% of cases. CONCLUSIONS: Double sensitization to grass and
      olive pollen is common in Spain and also occurs in the pediatric population.
      Molecular diagnosis using specific IgE may help improve immunotherapy selection
      in polysensitized patients.

PMID- 29369416
TI  - Complete tear of the lateral meniscus posterior root is associated with meniscal
      extrusion in anterior cruciate ligament deficient knees.
AB  - : This study aimed to evaluate the relationship between preoperative lateral
      meniscal extrusion (LME) and arthroscopic findings of lateral meniscus posterior
      root tear (LMPRT) in knees with anterior cruciate ligament (ACL) tear. Thirty
      five knees that had LMPRTs with concomitant ACL tears on arthroscopy were
      evaluated. Patients were divided into two groups, partial and complete root
      tears, via arthroscopic findings at the time of ACL reconstruction. For
      comparison, we added two groups, using the same database; 20 normal knees (normal
      group) and 20 ACL-injured knees without LM injury (intact LM group). We
      retrospectively measured preoperative LMEs using magnetic resonance imaging
      (MRI). Twenty-three knees had partial LMPRTs. Complete LMPRTs were observed in 12
      knees. The average LME was -0.1 +/- 0.4 mm in the normal group, 0.2 +/- 0.5 mm in
      the intact LM group, 0.4 +/- 0.8 mm in the partial LMPRT group, and 2.0 +/- 0.6
      mm in the complete LMPRT group. A significant difference in preoperative LMEs was
      observed between the complete LMPRT group and the other groups (p < 0.001). The
      receiver operating curve analysis, which distinguishes a partial tear from a
      complete tear, identified an optimal cut-off point of 1.1 mm for preoperative
      LME. This LME cut-off had a sensitivity of 100% and specificity of 83% for
      complete LMPRT. We found that preoperative LMEs were larger in complete LMPRTs
      associated with ACL injuries than in partial LMPRTs. Our results suggest that
      preoperative MRI-detected LME may be a useful indicator for estimating LMPRT
      severity in ACL-injured knees. LEVEL OF EVIDENCE: Retrospective comparative study
      level IV. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals,
      Inc. J Orthop Res 36:1894-1900, 2018.

PMID- 29369415
TI  - Cross-vendor harmonization of T2 -relaxation-under-spin-tagging (TRUST) MRI for
      the assessment of cerebral venous oxygenation.
AB  - PURPOSE: Cerebral venous oxygenation (Yv ) is an important physiological
      parameter and has potential clinical application in many brain diseases. T2 
      relaxation-under-spin-tagging (TRUST) is a commonly used MRI method to measure Yv
      . Harmonization of this technique across MRI vendors is important for
      dissemination and multicenter studies of brain oxygenation and metabolism as a
      disease biomarker. METHODS: TRUST pulse sequence components and imaging
      parameters were carefully matched between two major MRI vendors, Philips and
      Siemens. Each subject (N = 10) was scanned on both scanners within a 2.5-h
      period. On each scanner, the subject was scanned in two sessions to assess
      intersession reproducibility. A hyperoxia challenge was also included in both
      sessions and on both scanners to evaluate the sensitivity of the technique to Yv
      changes. Measured Yv values, confidence interval of Yv estimates ( epsilonYv), as
      well as intrasession and intersession coefficient of variation (CoV) of Yv , were
      compared between the two scanners. RESULTS: Yv measured on the two vendors were
      highly compatible and strongly correlated (R2  = 0.957). Yv changes associated
      with hyperoxia challenge were significant on both scanners (P < 0.001) and were
      also correlated across scanners (P = 0.007). Intrasession and intersession CoV of
      measured Yv were less than 3% and showed no difference between scanners.
      epsilonYv were less than 1% on both scanners and showed no difference between
      scanners when echo times were matched on the two scanners. CONCLUSION: This work
      suggests that harmonized TRUST MRI can yield highly compatible Yv measurements
      across different vendors. Magn Reson Med 80:1125-1131, 2018. (c) 2018
      International Society for Magnetic Resonance in Medicine.

PMID- 29369417
TI  - Characterization of NlHox3, an essential gene for embryonic development in
      Nilaparvata lugens.
AB  - Hox genes encode transcriptional regulatory proteins that control axial
      patterning in all bilaterians. The brown planthopper (BPH), Nilaparvata lugens
      (Hemiptera: Delphacidae), is a destructive insect pest of rice plants in Asian
      countries. During analysis of the N. lugens transcriptome, we identified a Hox3
      like gene (NlHox3) that was highly and specifically expressed in the embryonic
      stage. We performed functional analysis on the gene to identify its roles in
      embryonic development and its potential use as a target in RNA interference
      (RNAi) based pest control. The sequence analysis showed that NlHox3 was
      homologous to the Hox3 gene and was most closely related with zen of Drosophila.
      There were no significant differences in oviposition between the treated and
      control females after injecting double-stranded RNA of NlHox3 (dsNlHox3) into
      newly emerged female adult BPHs; however, there was a significant difference in
      the hatchability of those eggs laid, which no egg from the treated group hatched
      normally. Injecting female adult BPHs with dsNlHox3 led to necrosis of these
      offspring embryos, with eye reversal and undeveloped organs, suggesting that
      NlHox3 was an essential gene for embryonic development and might be a potential
      target for RNAi-based control of this insect pest.

PMID- 29369418
TI  - Next generation programming.

PMID- 29369419
TI  - The association between serum testosterone and mortality among elderly men on
      hemodialysis.
AB  - OBJECTIVES: This study examines the associations between total testosterone
      levels and dialysis mortality. METHODS: Elderly men who initiate hemodialysis in
      Taoyuan General Hospital from January 2012 to June 2017 were enrolled. We
      reviewed clinical characteristics and biochemical data from start of dialysis and
      followed over a 5-year period after dialysis. Body composition parameters were
      assessed 3-6 months after dialysis. Skeletal muscle mass index (SMMI) was defined
      by skeletal muscle mass divided by squared height. We defined those with lowest
      tertile of testosterone values as low testosterone group. Adjusted hazard ratios
      (aHRs) and 95% confidence interval (95% CI) for mortality and cumulative survival
      curves were evaluated by Cox hazards model and Kaplan-Meier method. The
      discriminative power of SMMI and testosterone levels was calculated according to
      the area under the curve and the receiver operating characteristic curve (AUROC).
      RESULTS: From a total of 137 elderly hemodialysis patients, the range of lowest,
      middle, and highest tertile of testosterone values was <6.25 nmol/L, 6.25-10.5
      nmol/L, and >10.5 nmol/L. After multivariate adjustment other than SMMI, total
      testosterone levels at baseline were a significant predictor for mortality
      aHR(95% CI): 0.79 (0.70-0.91). The unadjusted and adjusted c-statistics of SMMI
      vs testosterone values to predict overall were 770 (0.688-0.852) vs 0.779 (0.691
      0.866) and 855 (0.812-0.886) vs 0.812 (0.744-0.856) (Ps < .05), whereas the
      capacity of c-statistics was similar (chi2  = 0.143 and 2.709, Ps > .05).
      CONCLUSIONS: Total testosterone value was a predictor for mortality. It was
      noninferior to SMMI in predicting dialysis mortality.

PMID- 29369420
TI  - ATM and p53 combined analysis predicts survival in glioblastoma multiforme
      patients: A clinicopathologic study.
AB  - Glioblastoma is one of the most malignant cancers, with a distinguishing dismal
      prognosis: surgery followed by chemo- and radiotherapy represents the current
      standard of care, and chemo- and radioresistance underlie disease recurrence and
      short overall survival of patients suffering from this malignancy. ATM is a
      kinase activated by autophosphorylation upon DNA doublestrand breaks arising from
      errors during replication, byproducts of metabolism, chemotherapy or ionizing
      radiations; TP53 is one of the most popular tumor suppressor, with a preeminent
      role in DNA damage response and repair. To study the effects of the
      immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21
      cases were retrospectively examined. In normal brain tissue, p-ATM was expressed
      only in neurons; conversely, in tumors cells, the protein showed a variable
      cytoplasmic expression (score: +,++,+++), with being completely undetectable in
      three cases. Statistical analysis revealed that high p-ATM score (++/+++)
      strongly correlated to shorter survival (P = 0.022). No difference in overall
      survival was registered between p53 normally expressed (NE) and overexpressed
      (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the
      results from combined assessment of the two proteins showed that patients with NE
      p53 /low pATM score had longer overall survival than the NE p53/ high pATM score
      counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% =
      0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of
      p-ATM/p53 in glioblastomas and provided data on their possible
      prognostic/predictive of response role. A "non-oncogene addiction" to ATM for
      NEp53 glioblastoma could be postulated, strengthening the rationale for
      development of ATM inhibiting drugs.

PMID- 29369421
TI  - Genetic variation in IL28B (IFNL3) and response to interferon-alpha treatment in
      myeloproliferative neoplasms.
AB  - OBJECTIVE: In myeloproliferative neoplasms (MPN), interferon-alpha (IFN-alpha) is
      an effective treatment with disease-modifying properties but currently with no
      clear predictors of treatment outcome. Recent genomewide association studies in
      chronic hepatitis C have found a strong influence of genetic polymorphism near
      the IL28B (IFNL3) gene in response to IFN-alpha treatment. In this study, we
      sought to evaluate the prognostic impact of IL28B rs12979860, rs8099917, and
      rs12980275 on IFN-alpha treatment response in myeloproliferative neoplasms.
      METHOD: We retrospectively evaluated 100 patients with MPN treated with IFN
      alpha. The hematologic treatment response on IFN-alpha was compared between
      patients and correlated with host genetic variations in IL28B. The genotypes of
      IL28B were determined by allelic discrimination assays. RESULTS: The CC genotype
      of rs12979860 was found significantly associated with hematologic response in
      polycythemia vera (PV) with a complete response (CR) in 79% (CC) compared to 48%
      (non-CC), (P = .036). No association between the genotypes and treatment response
      on hydroxyurea was found. CONCLUSION: These results imply an effect of IL28B
      genotype on the outcome of IFN-alpha treatment in MPN.

PMID- 29369422
TI  - Cardiac-triggered pseudo-continuous arterial-spin-labeling: A cost-effective
      scheme to further enhance the reliability of arterial-spin-labeling MRI.
AB  - PURPOSE: Arterial-spin-labeling (ASL) magnetic resonance imaging (MRI) is
      intrinsically a low signal-to-noise ratio (SNR) technique. This study aims to
      enhance its sensitivity by quantifying physiological noise attributed to cardiac
      pulsation and devising an improved sequence, cardiac-triggered ASL, to minimize
      this noise. METHODS: A total of 16 healthy subjects were studied on a 3 Tesla MRI
      system. The influence of cardiac pulsation on pseudo-continuous ASL (pCASL)
      signal was first investigated by performing a regular pCASL sequence while the
      cardiac phase of the image acquisition was recorded by a pulse oximeter. We then
      designed a new sequence, cardiac-triggered pCASL, to align the cardiac phases of
      the control and labeled scans. The performance of the new sequence was evaluated
      in the context of single-shot 3D gradient-and-spin-echo acquisition, multishot 3D
      spiral acquisition, and hypercapnia-induced cerebral blood flow (CBF) changes.
      RESULTS: In regular pCASL, the signal intensities of both control and labeled
      images were strongly modulated by the cardiac phase. In single-shot acquisitions,
      this results in signal instability in regions near large vessels. In segmented
      acquisitions, it results in ghosting artifacts in the image and, furthermore, the
      signal fluctuation is smeared along the segmentation direction to affect more
      brain regions. Cardiac-triggered pCASL enhanced the temporal SNR by 94% and 28%
      in single-shot and segmented 3D acquisition, respectively. When applied to detect
      CBF changes, the triggered sequence revealed a greater statistical power in terms
      of both the number of significant voxels and t-score histograms. CONCLUSION:
      Cardiac-triggered pCASL represents a potential scheme to enhance the reliability
      of ASL signal. Magn Reson Med 80:969-975, 2018. (c) 2018 International Society
      for Magnetic Resonance in Medicine.

PMID- 29369423
TI  - Interstitial Mo-Assisted Photovoltaic Effect in Multilayer MoSe2
      Phototransistors.
AB  - Thin-film transistors (TFTs) based on multilayer molybdenum diselenide (MoSe2 )
      synthesized by modified atmospheric pressure chemical vapor deposition (APCVD)
      exhibit outstanding photoresponsivity (103.1 A W-1 ), while it is generally
      believed that optical response of multilayer transition metal dichalcogenides
      (TMDs) is significantly limited due to their indirect bandgap and inefficient
      photoexcitation process. Here, the fundamental origin of such a high
      photoresponsivity in the synthesized multilayer MoSe2 TFTs is sought. A unique
      structural characteristic of the APCVD-grown MoSe2 is observed, in which
      interstitial Mo atoms exist between basal planes, unlike usual 2H phase TMDs.
      Density functional theory calculations and photoinduced transfer characteristics
      reveal that such interstitial Mo atoms form photoreactive electronic states in
      the bandgap. Models indicate that huge photoamplification is attributed to
      trapped holes in subgap states, resulting in a significant photovoltaic effect.
      In this study, the fundamental origin of high responsivity with synthetic MoSe2
      phototransistors is identified, suggesting a novel route to high-performance,
      multifunctional 2D material devices for future wearable sensor applications.

PMID- 29369424
TI  - Non-contrast enhanced 4D intracranial MR angiography based on pseudo-continuous
      arterial spin labeling with the keyhole and view-sharing technique.
AB  - PURPOSE: 4D dynamic MR angiography (4D-MRA) using pseudo-continuous arterial spin
      labeling (pCASL), combined with Keyhole and View-sharing (4D-PACK) for scan
      acceleration, is introduced. Its validity for arterial inflow dynamics
      visualization was investigated through comparison with 4D-pCASL and contrast
      inherent inflow enhanced multiphase angiography (CINEMA). METHODS: Six healthy
      volunteers were included in the study. The arterial transit time (ATT) in 4D-PACK
      was measured at multiple regions in middle cerebral artery (MCA), and Pearson's
      correlation coefficient with ATT in 4D-pCASL was calculated. The contrast-to
      noise ratio (CNR) in 4D-PACK was measured in four MCA segments and compared with
      that in 4D-pCASL and CINEMA. Arterial visualization in 4D-PACK was assessed
      qualitatively in patients with moyamoya disease and arteriovenous malformation by
      comparing with CINEMA. RESULTS: 4D-PACK achieved a 36% scan time reduction
      compared with 4D-pCASL. The correlation coefficient for ATT measured by 4D-pCASL
      and 4D-PACK was greater than 0.96. The CNR was significantly higher using 4D-PACK
      compared with CINEMA in the M4 segment (P < 0.01). In patient examinations, the
      flow in the collateral artery or draining vein was better visualized in 4D-PACK
      compared with CINEMA. CONCLUSION: 4D-PACK accelerates 4D-pCASL, shows similar
      inflow dynamics as 4D-pCASL and shows better peripheral visualization compared
      with CINEMA. Magn Reson Med 80:719-725, 2018. (c) 2018 International Society for
      Magnetic Resonance in Medicine.

PMID- 29369425
TI  - Roles of Amphipathicity and Hydrophobicity in the Micelle-Driven Structural
      Switch of a 14-mer Peptide Core from a Choline-Binding Repeat.
AB  - Choline-binding repeats (CBRs) are ubiquitous sequences with a beta-hairpin core
      that are found in the surface proteins of several microorganisms such as S.
      pneumoniae (pneumococcus). Previous studies on a 14-mer CBR sequence derived from
      the pneumoccal LytA autolysin (LytA239-252 peptide) have demonstrated a switch
      behaviour for this peptide, so that it acquires a stable, native-like beta
      hairpin conformation in aqueous solution but is reversibly transformed into an
      amphipathic alpha-helix in the presence of detergent micelles. With the aim of
      understanding the factors responsible for this unusual beta-hairpin to alpha
      helix transition, and to specifically assess the role of peptide hydrophobicity
      and helical amphipathicity in the process, we designed a series of LytA239-252
      variants affecting these two parameters and studied their interaction with
      dodecylphosphocholine (DPC) micelles by solution NMR, circular dichroism and
      fluorescence spectroscopies. Our results indicate that stabilising cross-strand
      interactions become essential for beta-hairpin stability in the absence of
      optimal turn sequences. Moreover, both amphipathicity and hydrophobicity display
      comparable importance for helix stabilisation of CBR-derived peptides in
      micelles, indicating that these sequences represent a novel class of
      micelle/membrane-interacting peptides.

PMID- 29369426
TI  - Improving the Stability of Metal Halide Perovskite Materials and Light-Emitting
      Diodes.
AB  - Metal halide perovskites (MHPs) have numerous advantages as light emitters such
      as high photoluminescence quantum efficiency with a direct bandgap, very narrow
      emission linewidth, high charge-carrier mobility, low energetic disorder,
      solution processability, simple color tuning, and low material cost. Based on
      these advantages, MHPs have recently shown unprecedented radical progress
      (maximum current efficiency from 0.3 to 42.9 cd A-1 ) in the field of light
      emitting diodes. However, perovskite light-emitting diodes (PeLEDs) suffer from
      intrinsic instability of MHP materials and instability arising from the operation
      of the PeLEDs. Recently, many researchers have devoted efforts to overcome these
      instabilities. Here, the origins of the instability in PeLEDs are reviewed by
      categorizing it into two types: instability of (i) the MHP materials and (ii) the
      constituent layers and interfaces in PeLED devices. Then, the strategies to
      improve the stability of MHP materials and PeLEDs are critically reviewed, such
      as A-site cation engineering, Ruddlesden-Popper phase, suppression of ion
      migration with additives and blocking layers, fabrication of uniform bulk
      polycrystalline MHP layers, and fabrication of stable MHP nanoparticles. Based on
      this review of recent advances, future research directions and an outlook of
      PeLEDs for display applications are suggested.

PMID- 29369427
TI  - Pioglitazone/metformin adduct regulates insulin secretion and inhibits high
      glucose-induced apoptosis via p21-p53-MDM2 signaling in INS-1 cells.
AB  - Pioglitazone/metformin adduct is a novel compound synthesized from pioglitazone
      and metformin combined at a molar mass ratio of 1:1. The aim of this study was to
      investigate the effects of pioglitazone/metformin adduct on high glucose-induced
      insulin secretion and apoptosis in INS-1 cells. Western blot and CCK8 analyses
      showed that the death rate of INS-1 cells increased in response to glucose
      treatment in a concentration-dependent manner. ELISA assays and Western blot
      analyses showed that insulin secretion peaked following treatment with glucose
      concentration at 33.33 mM. Treatment of INS-1 cells with 1 MUM
      pioglitazone/metformin adduct in the presence of 33.33 mM glucose greatly
      improveded the levels of insulin and apoptosis rates compared to those of the
      control group. Analysis of mechanism underlying these effects revealed the
      involvement of the p21-p53-MDM2 signaling pathway. Our results indicate that
      pioglitazone/metformin adduct is superior to pioglitazone and/or metformin in
      regulating high glucose-induced insulin secretion and apoptosis in INS-1 cells.

PMID- 29369428
TI  - Chasing N-acetyl-L-aspartate, a shiny NMR object in the brain.

PMID- 29369429
TI  - Prebiotic Chemistry of HCN Tetramerization by Automated Reaction Search.
AB  - HCN oligomerization is considered to be one of the important pathways in chemical
      evolution. Nucleobases, aminoacids, and many other complex organic molecules can
      evolve through this pathway. We report an explorative study based on an automated
      reaction search method that avoids the cognitive bias present when searching
      chemical reaction space. We discuss the chemical space of the HCN dimer in
      detail, and the important trimers and tetramers are discussed briefly. A
      component-wise molecular-fingerprint-based methodology is proposed to identify
      molecular similarity. We present four different thermal routes to cis/trans-2,3
      diaminomaleonitrile and 4-amino-1H-imidazole-5-carbonitrile, which are important
      intermediates in prebiotic chemistry.

PMID- 29369430
TI  - Papain-treated panels are a simple method for the identification of
      alloantibodies in multiple myeloma patients treated with anti-CD38-based
      therapies.
AB  - OBJECTIVES: To report our 2 years of experience navigating the interference of
      anti-CD38 monoclonal antibodies (MAs) in 33 patients and describe papain-treated
      panels as a complementary method to dithiothreitol (DTT). BACKGROUND: Novel anti
      CD38 MAs are now approved or undergoing clinical trials to evaluate their
      activity in patients with multiple myeloma. A concern with the use of these drugs
      is that they interfere with blood bank tests in a group of patients who often
      require blood transfusions. METHODS: Clinical data and whole blood samples were
      collected from patients receiving daratumumab or isatuximab. Routine blood bank
      serological tests were performed. RESULTS: A total of 9.1% of patients presented
      with alloantibodies prior to treatment. All patients exhibited nonspecific
      reactivity in indirect antiglobulin tests, and 26% had positive direct
      antiglobulin tests after beginning treatment. This interference disappeared in
      all patients after discontinuing treatment. Papain panels avoided this reactivity
      and allowed us to identify alloantibodies. Phenotyped blood units were
      transfused, and no patient suffered any transfusion-related complications.
      CONCLUSION: Anti-CD38 MAs produce nonspecific interference in blood bank tests.
      This interference can be overcome by various methods, including DTT or papain
      treatment as proposed here. These methods have limitations that can be resolved
      using phenotyped blood units.

PMID- 29369432
TI  - Corrigendum for: Do bilinguals automatically activate their native language when
      they are not using it?

PMID- 29369431
TI  - Inhibitor-Directed Spin Labelling-A High Precision and Minimally Invasive
      Technique to Study the Conformation of Proteins in Solution.
AB  - Pulsed electron-electron double resonance spectroscopy (known as PELDOR or DEER)
      has recently become a very popular tool in structural biology. The technique can
      be used to accurately measure distance distributions within macromolecules or
      macromolecular complexes, and has become a standard method to validate structural
      models and to study the conformational flexibility of macromolecules. It can be
      applied in solution, in lipid environments or even in cells. Because most
      biological macromolecules are diamagnetic, they are normally invisible for PELDOR
      spectroscopy. To render a particular target molecule accessible for PELDOR, it
      can be engineered to contain only one or two surface-exposed cysteine residues,
      which can be efficiently spin-labelled using thiol-reactive nitroxide compounds.
      This method has been coined "site-directed spin labelling" (SDSL) and is normally
      straight-forward. But, SDSL can be very challenging for proteins with many native
      cysteines, or even a single functionally or structurally important cysteine
      residue. For such cases, alternative spin labelling techniques are needed. Here
      we describe the concept of "inhibitor-directed spin labelling" (IDSL) as an
      approach to spin label suitable cysteine-rich proteins in a site-directed and
      highly specific manner by employing bespoke spin-labelled inhibitors. Advantages
      and disadvantages of IDSL are discussed.

PMID- 29369433
TI  - Comparing the fragmentation reactions of protonated cyclic indolyl alpha-amino
      esters in quadrupole/orbitrap and quadrupole time-of-flight mass spectrometers.
AB  - RATIONALE: The comparative study of higher-energy collisional dissociation (HCD)
      and collision-induced dissociation (CID) mechanisms for protonated cyclic indolyl
      alpha-amino esters in quadrupole/orbitrap (Q/Orbitrap) and quadrupole time-of
      flight (QTOF) mass spectrometers, respectively, is helpful to study the
      structures and properties of biologically active indole derivatives using tandem
      mass spectrometry (MS/MS) technology. METHODS: HCD and CID experiments were
      carried out using electrospray ionization Q/Orbitrap MS and QTOFMS in positive
      ion mode, respectively. Only the labile hydrogens were exchanged with deuterium
      in hydrogen/deuterium exchange (HDX) experiments and only the aromatic indole C-H
      hydrogens were substituted with deuterium in regiospecific hydrogen-deuterium
      labeling experiments. Theoretical calculations were carried out using the density
      functional theory (DFT) method at the B3LYP level with the 6-311G(d,p) basis set
      in the Gaussian 03 package of programs. RESULTS: In Q/Orbitrap MS/MS, when the
      added proton on the N8 position of protonated cyclic indolyl alpha-amino esters
      migrated in a stepwise fashion to the C3 position via two sequential 1,4-H
      shifts, an ion-neutral complex INC1 of [protonated cyclic N-sulfonyl ketimino
      esters/indoles] was formed by a charge-directed heterolytic cleavage of the C3 
      C10 bond, while an ion-neutral complex INC3 of [cyclic N-sulfonyl ketimino
      esters/protonated indoles] was formed when another labile hydrogen on the N8
      position successively migrated to the C4 position. Direct decomposition of INC1
      and INC3 resulted in protonated cyclic N-sulfonyl ketimino esters and protonated
      indoles, respectively, while proton transfer led to protonated indoles and
      protonated cyclic N-sulfonyl ketimino esters. The HDX reaction with residual
      water in the HCD cell was also observed. In QTOF-MS/MS, protonated cyclic N
      sulfonyl ketimino esters and protonated indoles resulted from direct
      decomposition of INC1 and INC3 , respectively, rather than proton transfer.
      CONCLUSIONS: Due to the specific construction of the Q/Orbitrap and QTOF mass
      spectrometers, different fragmentation mechanisms medicated by ion-neutral
      complexes of protonated cyclic indolyl alpha-amino esters were proposed. This
      study is desirable for qualitative and quantitive investigation of indole
      derivatives using MS/MS technology.

PMID- 29369434
TI  - Lipopolysaccharide-induced maternal inflammation induces direct placental injury
      without alteration in placental blood flow and induces a secondary fetal
      intestinal injury that persists into adulthood.
AB  - PROBLEM: Premature birth complicates 10%-12% of deliveries. Infection and
      inflammation are the most common etiologies and are associated with increased
      offspring morbidity and mortality. We hypothesize that lipopolysaccharide (LPS)
      induced maternal inflammation causes direct placenta injury and subsequent injury
      to the fetal intestine. METHOD OF STUDY: Pregnant C57Bl6 mice were injected
      intraperitoneally on day 15.5 with 100 MUg/kg LPS or saline. Maternal serum,
      amniotic fluid, placental samples, and ileal samples of offspring were obtained
      assessed for inflammation and/or injury. Maternal placental ultrasounds were
      performed. Placental DNA was isolated for microbiome analysis. RESULTS: Maternal
      injection with LPS caused elevated IL-1beta, IL-10, IL-6, KC-GRO, and TNF.
      Placental tissue showed increased IL-1beta, IL-6, and KC-GRO and decreased IL-10,
      but no changes were observed in amniotic fluid. Placental histology demonstrated
      LPS-induced increases in mineralization and necrosis, but no difference in
      placental blood flow. Most placentas had no detectable microbiome. Exposure to
      maternal LPS induced significant injury to the ilea of the offspring. CONCLUSION:
      Lipopolysaccharide causes a maternal inflammatory response that is mirrored in
      the placenta. Placental histology demonstrates structural changes; however,
      placental blood flow is preserved. LPS also induces an indirect intestinal injury
      in the offspring that lasts beyond the neonatal period.

PMID- 29369436
TI  - Sphingomyelin in microdomains of the plasma membrane regulates amino acid
      stimulated mTOR signal activation.
AB  - Sphingomyelin (SM) is required for cells to proliferate, but the reason is not
      fully understood. In order to asses this question, we employed a cell line, ZS,
      which lacks both SMS1 and SMS2, isolated from mouse embryonic fibroblasts in SMS1
      and 2 double knockout mouse, and SMS1 or SMS2 re-expressing cells, ZS/SMS1 or
      ZS/SMS2, respectively. We investigated regulation of SM in activating the
      mammalian target of rapamycin (mTOR) signal induced by essential amino acids
      (EAA), using these cells. EAA-stimulated mTOR signal was more activated in
      ZS/SMS1 and ZS/SMS2 cells than in controls. Treatment with methyl-b-cyclodextrin
      dramatically inhibited the activation. Interestingly, we found that the
      expression of CD98, LAT-1 and ASCT-2, amino acid transporters concerned with mTOR
      activation, was down-regulated in ZS cells. Transporters localized in
      microdomains and formed a functional complex. Our results indicate that SM affect
      proliferation through the transport of amino acids via SM-enriched microdomains.

PMID- 29369435
TI  - Design of Protein-Coated Carbon Nanotubes Loaded with Hydrophobic Drugs through
      Sacrificial Templating of Mesoporous Silica Shells.
AB  - One key challenge in the fields of nanomedicine and tissue engineering is the
      design of theranostic nanoplatforms able to monitor their therapeutic effect by
      imaging. Among current developed nano-objects, carbon nanotubes (CNTs) were found
      suitable to combine imaging, photothermal therapy, and to be loaded with
      hydrophobic drugs. However, a main problem is their resulting low hydrophilicity.
      To face this problem, an innovative method is developed here, which consists in
      loading the surface of carbon nanotubes (CNTs) with drugs followed by a protein
      coating around them. The originality of this method relies on first covering CNTs
      with a sacrificial template mesoporous silica (MS) shell grafted with
      isobutyramide (IBAM) binders on which a protein nanofilm is strongly adhered
      through IBAM-mediated physical cross-linking. This concept is first demonstrated
      without drugs, and is further improved with the suitable loading of hydrophobic
      drugs, curcumin (CUR) and camptothecin (CPT), which are retained between the CNTs
      and human serum albumin (HSA) layer. Such novel nanocomposites with favorable
      photothermal properties are very promising for theranostic systems, drug
      delivery, and phototherapy applications.

PMID- 29369437
TI  - Best practice in critical care: anaemia in acute and critical illness.
AB  - Anaemia is common in critical illness, and standard treatment is red blood cell
      (RBC) transfusion, typically using a restrictive transfusion threshold of 70 g L
      1 . However, there are subgroups of patients in whom it is biologically plausible
      that a higher transfusion threshold may be beneficial, namely, acute sepsis,
      traumatic brain injury and coexisting cardiovascular disease. In this review
      article, we will discuss the pathophysiology of anaemia, as well as its
      prevalence and time course. We will explore the limitations of using haemoglobin
      concentration as a surrogate for oxygen delivery and the concept of the critical
      haemoglobin concentration. We will then discuss transfusion thresholds for the
      general intensive care unit (ICU) population and specific subgroups.

PMID- 29369438
TI  - Asymmetric Catalytic Double Michael Additions for the Synthesis of
      Spirooxindoles.
AB  - Asymmetric cascade double Michael additions to construct 2'-substituted 3,3'
      spirooxindoles by using a chiral guanidine organocatalyst has been developed. A
      series of spirooxindole derivatives containing dihydrofuran or pyrrolidine
      subunits were obtained with good to excellent diastereo- and
      enantioselectivities. The method showed great tolerance of a number of aromatic
      and aliphatic alkynones. The strategy gave access to the asymmetric synthesis of
      (-)-salacin for the first time.

PMID- 29369439
TI  - Cabazitaxel inhibits proliferation and potentiates the radiation response of
      U87MG glioblastoma cells.
AB  - Cabazitaxel is a second-generation semisynthetic taxane. The recognized anti
      neoplastic effect of Cabazitaxel is cell cycle perturbation by inducing arrest at
      G2/M. Since glioblastoma tumors have a relatively high expression of P-gp, it is
      encouraging to find a treatment that is effective against these tumors. This
      study was conducted to examine the radiosensitizing potential of Cabazitaxel
      against U87MG cells. In order to evaluate the effect of Cabazitaxel, cells were
      treated with different concentrations of the drug at different time intervals and
      then cytotoxicity and cell cycle were assessed using MTT and flow cytometry
      assays, respectively. Annexin/PI and real-time polymerase chain reaction (PCR)
      assays were used to evaluate the extent of apoptosis. Cabazitaxel exerted a
      consistent G2/M arrest and resulted in a concentration- and time-dependent
      toxicity. Cabazitaxel enhanced the cytotoxicity response of U87MG cells to
      radiation. Apoptosis increased following Cabazitaxel-IR administration. At the
      same time, these results were further supported by apoptotic genes regulation.
      This study provides the first preclinical evidence supporting that Cabazitaxel
      can render U87MG cells more susceptible to the cytotoxicity of radiation and
      could potentially be administered in combination modalities as a promising cell
      cycle-specific radiosensitizer for the future steps of in vivo evaluation.

PMID- 29369440
TI  - Synthesis and Properties of Triaminocyclopropenium Cation Based Ionic Liquids as
      Hypergolic Fluids.
AB  - A novel family of hydrophobic triaminocyclopropenium cation based ionic liquids
      have been synthesized, and their structures and physicochemical properties
      characterized by NMR and IR spectroscopy, elemental analysis, differential
      scanning calorimetry, and hypergolic tests. The experimental results showed that
      all of these ionic liquids exhibited the expected hypergolic reactivity with the
      oxidizer white fuming nitric acid. Among them, the hypergolic ionic liquid based
      on the cyanoimidazolylborohydride anion showed excellent integrated properties,
      including high decomposition temperature (194  degrees C), high density (0.95 g
      cm-3 ), moderate viscosity (44 MPa s), ultrafast ignition delay time (6 ms), and
      high specific impulse (301.9 s); this demonstrates its potential as an
      environmentally friendly alternative to toxic hydrazine derivatives.

PMID- 29369441
TI  - Repeat ablation or medical management alone for recurrent arrhythmias after
      ablation of persistent atrial fibrillation.
AB  - INTRODUCTION: Management of persistent atrial fibrillation (PersAF) remains
      challenging, and many patients are left on medical therapy after a failed first
      ablation. In patients with recurrent symptomatic arrhythmias after PersAF
      ablation, we aimed to compare outcomes of repeat ablation and medical therapy
      versus medical therapy alone. METHODS AND RESULTS: All 682 consecutive patients
      with recurrent symptomatic arrhythmia after a first ablation for PersAF at our
      institution (2005-2012) were included. Repeat ablation with continuation of
      medical therapy was performed in 364 patients (Group 1) and 318 were only
      medically managed (Group 2). The outcome of interest was freedom from arrhythmia
      recurrence beyond a 3-month blanking period. Separate analyses were performed to
      assess this endpoint totally off antiarrhythmics (primary endpoint) or
      alternatively with/without use of antiarrhythmics (secondary endpoint). Over a
      median follow-up of 26 months, 41.5% of Group 1 patients met the primary endpoint
      and remained free from arrhythmia recurrence off antiarrhythmics (vs. 14.5% in
      Group 2, P < 0.0001). At last follow-up, antiarrhythmics continued to be required
      for rhythm control in 40.1% and 46.2% of patients in Groups 1 and 2, respectively
      (P < 0.0001). The secondary endpoint was met in 60.2% versus 32.1% of patients in
      Groups 1 and 2, respectively (P < 0.0001). In multivariable Cox analyses, repeat
      ablation was associated with significant reduction in arrhythmia recurrences
      compared to medical therapy alone (HR 0.48, 95% CI 0.35-0.65, P < 0.0001).
      CONCLUSION: In patients with recurrent symptomatic arrhythmia after ablation of
      PersAF, repeat ablation was associated with significant reduction in arrhythmia
      recurrences compared to routine medical therapy alone.

PMID- 29369442
TI  - Negative nucleotide ions as sensitive probes for energy specificity in collision
      induced fragmentation in mass spectrometry.
AB  - RATIONALE: The most commonly used fragmentation methods in tandem mass
      spectrometry (MS/MS) are collision-induced dissociation (CID) and higher energy
      collisional dissociation (HCD). While in CID the preselected ions in the trap are
      resonantly (and m/z exclusively) excited, in HCD the entire m/z range experiences
      the dissociative acceleration. The different excitation is reflected in different
      fragment distributions. METHODS: As a test-bed for particularly pronounced
      fragmentation specificity, here MS/MS experiments on several 4-mer
      oligonucleotides were conducted employing both collision methods and the results
      were thoroughly compared. Oligonucleotides are shown to be sensitive probes to
      subtle changes, especially in the negative ion mode. A detailed analysis of these
      differences reveals insight into the dissociation mechanics. RESULTS: The
      differences are represented in heat-maps, which allow for a direct visual
      inspection of large amounts of data. In these false colour representations the,
      sometimes subtle, changes in the individual dissociation product distributions
      become distinct. Another advantage of these graphic plots can be found in the
      formation of systematic patterns. These patterns reflect trends in dissociation
      specificity which allow for the formulation of general rules in fragmentation
      behavior. CONCLUSIONS: Instruments equipped with two different excitation schemes
      for MS/MS are today widely available. Nonetheless, direct comparisons between the
      individual results are scarcely made. Such comparative studies bear a powerful
      analytical potential to elucidate fragmentation reaction mechanism.

PMID- 29369443
TI  - Carbon-Dots-Based Lab-On-a-Nanoparticle Approach for the Detection and
      Differentiation of Antibiotics.
AB  - Fluorescent carbon dots (CDs) have received considerable attention in recent
      years due to their superior optical properties. To take further advantages of
      these unique features, herein, a CDs-based "lab-on-a-nanoparticle" approach for
      the detection and discrimination of antibiotics is developed. The sensing
      platform was designed based on the different channel's fluorescence recoveries or
      further quenching of the full-color emissive CDs (F-CDs) and metal ion ensembles
      upon the addition of antibiotics. The F-CDs exhibited unusually comparable
      emission intensity nearly across the entire visible spectrum even as the
      excitation wavelength is shifted, making it very suitable for the construction of
      multi-channel sensing systems. The sensing platform was fabricated on the basis
      of the competing interaction of metal ions with the F-CDs and antibiotics. Three
      metal ions (i.e., Cu2+ , Ce3+ and Eu3+ ) can efficiently quench the fluorescence
      of the F-CDs. Upon the addition of antibiotics, the fluorescent intensities
      either recovered at different emission wavelengths or were further quenched to
      various degrees. The fluorescence response patterns at different emission
      wavelength were characteristic for each antibiotic and can be quantitatively
      differentiated by standard statistical methods (e.g., hierarchical clustering
      analysis and principal component analysis). Moreover, as an example, the proposed
      method was applied for quantitative detection of oxytetracycline with a limit of
      detection to be 0.06 MUm. Finally, the sensing system was successfully employed
      for residual antibiotics detection and identification in real food samples.

PMID- 29369444
TI  - Exploring the Effect of Polypyridyl Ligands on the Anticancer Activity of
      Phosphorescent Iridium(III) Complexes: From Proteosynthesis Inhibitors to
      Photodynamic Therapy Agents.
AB  - A series of five kinetically inert bis-cyclometalated IrIII complexes of general
      formula [Ir(C^N)2 (N^N)][PF6 ] [C^N=2-phenyl-1-[4-(trifluoromethyl)benzyl]-1H
      benzo[d]imidazol-kappaN,C; N^N=1,10-phenanthroline (phen, 1), dipyrido[3,2
      d:2',3'-f]quinoxaline (dpq, 2), dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3),
      benzo[i]dipyrido[3,2-a:2',3'-c]phenazine (dppn, 4), and dipyrido[3,2-a:2',3'
      c]phenazine-10,11-imidazolone (dppz-izdo, 5)] were designed and synthesized to
      explore the effect of the degree of pi conjugation of the polypyridyl ligand on
      their toxicity in cancer cells. We show that less-lipophilic complexes 1 and 2
      exhibit the highest toxicity [sub-micromolar inhibitory concentration (IC50 )
      values] in A2780, HeLa, and MCF-7 cancer cells, and they are markedly more
      efficient than clinically used platinum drugs. It is noteworthy that the
      investigated Ir agents display the capability to overcome acquired and inherent
      resistance to conventional cisplatin (in A2780cisR and MCF-7 cells,
      respectively). We demonstrate that the Ir complexes, unlike clinically used
      platinum antitumor drugs, do not kill cells through DNA-damage response. Rather,
      they kill cells by inhibiting protein translation by targeting preferentially the
      endoplasmic reticulum. Our findings also reveal that the toxic effect of the Ir
      complexes can be significantly potentiated by irradiation with visible light (by
      more than two orders of magnitude). The photopotentiation of the investigated Ir
      complexes can be attributed to a marked increase (~10-30-fold) in intracellular
      reactive oxygen species. Collectively, these data highlight the functional
      diversity of antitumor metal-based drugs and the usefulness of a mechanism-based
      rationale for selecting candidate agents that are effective against
      chemoresistant tumors for further preclinical testing.

PMID- 29369445
TI  - Selected maternal, fetal and placental trace element and heavy metal and maternal
      vitamin levels in preterm deliveries with or without preterm premature rupture of
      membranes.
AB  - AIM: To compare maternal, fetal and placental trace element (magnesium, zinc and
      copper) and heavy metal (cadmium and lead) and maternal vitamin (retinol, alpha
      [alpha]-tocopherol, vitamin D3 , 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin
      D3 ) levels in preterm deliveries with and without preterm premature rupture of
      membranes (PPROM). METHODS: Sixty-eight patients giving birth preterm were
      grouped into preterm deliveries with PPROM (n = 35) and without PPROM (n = 33).
      Following delivery, maternal and umbilical cord blood sera and placental tissue
      samples were obtained. While magnesium, zinc, copper, cadmium and lead levels
      were measured in all samples, the levels of retinol, alpha-tocopherol, vitamin D3
      , 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 were measured only in
      maternal serum. RESULTS: While magnesium level in maternal serum and zinc levels
      in both maternal and umbilical cord sera were lower, placental magnesium level
      was higher in preterm deliveries with PPROM (P < 0.01). Umbilical cord serum
      magnesium, placental tissue zinc and maternal and umbilical cord sera and
      placental tissue copper, cadmium, and lead levels did not differ between the
      groups (P > 0.05). In preterm deliveries with PPROM, 25-hydroxyvitamin D3 and
      retinol levels were higher, while vitamin D3 and 1,25-dihydroxyvitamin D3 levels
      were lower in maternal serum (P < 0.05). Maternal serum alpha-tocopherol levels
      were similar between the groups. CONCLUSION: Compared to spontaneous preterm
      births, PPROM is associated with low maternal serum together with high placental
      tissue magnesium and low maternal and umbilical cord sera zinc levels. Higher
      retinol and 25-hydroxyvitamin D3 and lower vitamin D3 and 1,25-dihydroxyvitamin
      D3 maternal serum levels are also evident in these patients.

PMID- 29369446
TI  - Objective assessment of induced acute pain in neonatology with the Newborn Infant
      Parasympathetic Evaluation index.
AB  - BACKGROUND: Objective tools are needed to improve pain assessment in newborns.
      The aim of this study was to assess the correlation between the Newborn Infant
      Parasympathetic Evaluation (NIPE) index and two pain scales during a painful
      procedure in premature infants. METHOD: Each baby born at least at 26 weeks of
      gestational age (GA) undergoing a planned painful procedure in the Neonatal
      Intensive Care Unit (NICU) was eligible. NIPE index, heart rate variability (HRV)
      indices and Neonatal Acute Pain scale (DAN) were recorded across three periods:
      the first at rest 5 min before the painful procedure (T1), the second during it
      (T2) and the third 3 min after the end of it (T3). The Premature Infant Pain
      Profile-Revised (PIPP-R) pain scale was recorded at T2. RESULTS: Sixty-four
      recordings were performed in 29 preterm infants (mean GA = 29.9 +/- 4.2 weeks).
      Twenty-eight tachograms were coupled to NIPE for analysis. We did not find a
      correlation between the NIPE index and DAN and PIPP-R at the pain time T2.
      Between T1 and T2, heart rate was higher (159 +/- 16 vs. 169 +/- 12, p < 0.001).
      Considering the linear HRV indices, we did not observe a modification in
      parasympathetic or sympathetic activity, while for the nonlinear HRV indices (H
      exponent, Approximate and conditional Entropy), a significant change towards a
      loss of physiological chaotic cardiac behaviour was detected. CONCLUSIONS: The
      NIPE index seems to be not reliable to assess acute pain in the preterm infant,
      but other HRV indices could be explored as additional tools next to pain scales
      in NICUs. SIGNIFICANCE: The NIPE monitor was developed for objective pain
      assessment in neonates based on HFnu variations, but it does not seem reliable
      enough for assessing acute pain in real time in preterm neonates. Pain assessment
      in preterm babies still relies on pain scales.

PMID- 29369448
TI  - Prevalence of axis II comorbidities in bipolar disorder: relationship to mood
      state.
AB  - OBJECTIVES: A high incidence of Axis II personality disorders is described in
      patients with bipolar disorder; however, their relationship to mood state remains
      uncertain. METHODS: A total of 966 outpatients with bipolar disorder gave
      informed consent and filled out the Personality Disorder Questionnaire, 4th
      edition (PDQ4) and a questionnaire on demographics and course of illness prior to
      Bipolar Treatment Outcome Network entry at average age 41 years. Patients were
      rated at each visit for depression on the Inventory of Depressive Symptoms
      Clinician version (IDS-C) and for mania on the Young Mania Rating Scale (YMRS).
      In a subgroup, the PDQ4 was retaken during periods of depression and euthymia.
      RESULTS: Patients met criteria for most personality disorders at a much higher
      rate when they took the PDQ4 while depressed compared to while euthymic, and
      scores were significantly related to the severity of depression (IDS) and of
      mania (YMRS) assessed within 2 weeks of taking the PDQ. Even when euthymic, more
      than quarter to half of the patients met criteria for a cluster A, B or C
      personality disorder. CONCLUSIONS: A wide range of personality disorders occur in
      bipolar patients, but are highly dependent on filling out the form while
      depressed compared to while euthymic. How this relates to having a personality
      disorder assessed using a structured clinical interview remains to be tested.
      However, higher PDQ4 scores are related to an earlier age of onset of bipolar
      disorder and other factors portending a more difficult course of bipolar
      disorder, and the optimal treatment of these patients remains to be illuminated.

PMID- 29369449
TI  - Biomarkers for acute kidney injury in decompensated cirrhosis: A Prospective
      Study.
AB  - BACKGROUND: Acute kidney injury (AKI) is a frequent complication in cirrhotic
      patients. As serum creatinine is a poor marker of renal function in this
      population, we aimed to study the utility of several biomarkers in this context.
      METHODS: A prospective study was conducted in hospitalized patients with
      decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and
      urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate
      occasions. Renal resistive index (RRI) was obtained. We analyzed the value of
      these biomarkers to determine the presence of AKI, its etiology [prerenal, acute
      tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite
      clinical outcome at 30 days (death, dialysis and intensive care admission).
      RESULTS: We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma
      and urinary), urinary sodium and RRI at inclusion were independently associated
      with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the
      subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL
      (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and
      urinary) as well as urinary protein and sodium. HRS patients presented an
      intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC
      and plasma NGAL predicted the development of the composite clinical outcome with
      the same performance as the MELD score. CONCLUSIONS: In patients with
      decompensated cirrhosis, early measurement of renal biomarkers provides valuable
      information on AKI etiology. It could also improve AKI diagnosis and prognosis.

PMID- 29369450
TI  - Pain and sensitization after total knee replacement or nonsurgical treatment in
      patients with knee osteoarthritis: Identifying potential predictors of outcome at
      12 months.
AB  - BACKGROUND: This study is a secondary analysis of 12-month follow-ups from two
      parallel, randomized controlled trials (RCT) in painful knee osteoarthritis
      patients. RCT1: Total knee replacement (TKR) followed by nonsurgical treatment
      compared with nonsurgical treatment. RCT2: Nonsurgical treatment compared with
      usual care. The aims were to investigate (1) possible predictors of treatment
      outcome after TKR and nonsurgical interventions at 12 months, (2) associations
      between pain intensity and pressure pain thresholds (PPTs) (pain sensitization)
      at baseline and after 12 months and (3) possible gender differences. METHOD: Each
      RCT included 100 patients. Pain intensities, PPTs and number of painful sites
      were assessed at baseline and after 12 months. RESULTS: In all groups, pain
      improved and pain sensitization decreased. In RCT1, the TKR group had the
      greatest improvements in pain. In RCT2 the nonsurgical group had the greatest
      improvement, with no between-group differences in PPTs. Lower PPTs at baseline
      predicted higher pain after TKR. Baseline pain intensity and PPT levels were
      associated with the number of painful sites. Subjects with the highest pain and
      lowest PPTs at baseline showed the largest relative improvement in pain and
      sensitization but were still experiencing highest absolute pain and lowest PPTs
      after 12 months (combined cohorts). CONCLUSION: Low PPTs at baseline predicted
      worse pain outcome after TKR, but did not predict outcome after nonsurgical
      interventions. The number of painful sites was weakly associated with pain and
      PPTs, and the higher pain/lower PPTs, the higher pain/lower PPTs at 12 months
      with females showing the lowest PPT values. SIGNIFICANCE: Human experimental pain
      assessment was used to assess the degree of pain sensitization in patients with
      painful knee osteoarthritis. High sensitization before TKR predicted worse
      outcome. Outcome after nonsurgical interventions could not be predicted.

PMID- 29369451
TI  - Feasibility of single-shot multi-level multi-angle diffusion tensor imaging of
      the human cervical spinal cord at 7T.
AB  - PURPOSE: Diffusion tensor imaging (DTI), which is frequently used to characterize
      microstructure impairments in many spinal cord diseases at clinical fields, may
      benefit from 7T investigations. Yet, it presents specific technical challenges,
      such as increased magnetic susceptibility-induced image distortions. METHODS:
      Eight healthy volunteers were scanned at 7T using a prototype diffusion multi
      slice multi-angle (MSMA) single-shot spin-echo echo planar imaging (EPI) sequence
      developed to explore the whole cervical spinal cord while limiting the partial
      volume effects related to the cord curvature. To mitigate the increased
      susceptibility-induced distortions encountered at 7T, a reverse phase-encoding
      strategy was also used. Images acquired from C1-to-C7 were registered to the
      AMU40 template to automatically extract DTI metrics in gray matter/white matter
      regions of interest. Effects of B1+ inhomogeneities on the DTI metrics and
      repeatability of the measurements were also investigated. Lastly, a DTI
      acquisition with a 400-um in-plane resolution was acquired on one volunteer to
      push forward 7T potentialities. RESULTS: The MSMA sequence allowed accessing to
      high-resolution axial diffusion images sampling the whole cord within a single
      acquisition. DTI metrics were found in agreement with literature at lower field,
      stable along a 50-120% relative B1+ variation range, with a mean inter-scan
      coefficient of variation of 8%. The two--fold spatial-resolution increase of the
      additional DTI acquisition enabled main white matter tracts visualization on a
      single-subject basis. CONCLUSION: Although C7-level imaging needs some
      improvement, this preliminary study shows that transverse 7T DTI of the whole
      cervical spinal cord is feasible, laying the groundwork for improved multi
      parametric MR investigations and microstructure characterization of the spinal
      cord. Magn Reson Med 80:947-957, 2018. (c) 2018 International Society for
      Magnetic Resonance in Medicine.

PMID- 29369447
TI  - Critical reappraisal of mechanistic links of copy number variants to dimensional
      constructs of neuropsychiatric disorders in mouse models.
AB  - Copy number variants are deletions and duplications of a few thousand to million
      base pairs and are associated with extraordinarily high levels of autism spectrum
      disorder, schizophrenia, intellectual disability, or attention-deficit
      hyperactivity disorder. The unprecedented levels of robust and reproducible
      penetrance of copy number variants make them one of the most promising and
      reliable entry points to delve into the mechanistic bases of many mental
      disorders. However, the precise mechanistic bases of these associations still
      remain elusive in humans due to the many genes encoded in each copy number
      variant and the diverse associated phenotypic features. Genetically engineered
      mice have provided a technical means to ascertain precise genetic mechanisms of
      association between copy number variants and dimensional aspects of mental
      illnesses. Molecular, cellular, and neuronal phenotypes can be detected as
      potential mechanistic substrates for various behavioral constructs of mental
      illnesses. However, mouse models come with many technical pitfalls. Genetic
      background is not well controlled in many mouse models, leading to rather obvious
      interpretative issues. Dose alterations of many copy number variants and single
      genes within copy number variants result in some molecular, cellular, and
      neuronal phenotypes without a behavioral phenotype or with a behavioral phenotype
      opposite to what is seen in humans. In this review, I discuss technical and
      interpretative pitfalls of mouse models of copy number variants and highlight
      well-controlled studies to suggest potential neuronal mechanisms of dimensional
      aspects of mental illnesses. Mouse models of copy number variants represent
      toeholds to achieve a better understanding of the mechanistic bases of dimensions
      of neuropsychiatric disorders and thus for development of mechanism-based
      therapeutic options in humans.

PMID- 29369452
TI  - Accuracy of Computed Tomography in Diagnosis of Intra-abdominal Injuries in
      Stable Patients With Anterior Abdominal Stab Wounds: A Systematic Review and Meta
      analysis.
AB  - BACKGROUND: Workup for patients presenting to the emergency department (ED)
      following an anterior abdominal stab wound (AASW) has been debated since the
      1960s. Experts agree that patients with peritonitis, evisceration, or hemodynamic
      instability should undergo immediate laparotomy (LAP); however, workup of stable,
      asymptomatic or nonperitoneal patients is not clearly defined. OBJECTIVES: The
      objective was to evaluate the accuracy of computed tomography of abdomen and
      pelvis (CTAP) for diagnosis of intraabdominal injuries requiring therapeutic
      laparotomy (THER-LAP) in ED patients with AASW. Is a negative CT scan without a
      period of observation sufficient to safely discharge a hemodynamically stable,
      asymptomatic AASW patient? METHODS: We searched PubMed, Embase, and Scopus from
      their inception until May 2017 for studies on ED patients with AASW. We defined
      the reference standard test as LAP for patients who were managed surgically and
      inpatient observation in those who were managed nonoperatively. In those who
      underwent LAP, THER-LAP was considered as disease positive. We used the Quality
      Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2) to evaluate the risk
      of bias and assess the applicability of the included studies. We attempted to
      compute the pooled sensitivity, specificity, positive likelihood ratio (LR+), and
      negative likelihood ratio (LR-) using a random-effects model with MetaDiSc
      software and calculate testing and treatment thresholds for CT scan applying the
      Pauker and Kassirer model. RESULTS: Seven studies were included encompassing 575
      patients. The weighted prevalence of THER-LAP was 34.3% (95% confidence interval
      [CI] = 30.5%-38.2%). Studies had variable quality and the inclusion criteria were
      not uniform. The operating characteristics of CT scan were as follows:
      sensitivity = 50% to 100%, specificity = 39% to 97%, LR+ = 1.0 to 15.7, and LR- =
      0.07 to 1.0. The high heterogeneity (I2  > 75%) of the operating characteristics
      of CT scan prevented pooling of the data and therefore the testing and treatment
      thresholds could not be estimated. DISCUSSION: The articles revealed a high
      prevalence (8.7%, 95% CI = 6.1%-12.2%) of injuries requiring THER-LAP in patients
      with a negative CT scan and almost half (47%, 95% CI = 30%-64%) of those injuries
      involved the small bowel. CONCLUSIONS: In stable AASW patients, a negative CT
      scan alone without an observation period is inadequate to exclude significant
      intraabdominal injuries.

PMID- 29369454
TI  - Comparative study of Helicobacter pylori eradication rates of concomitant therapy
      vs modified quadruple therapy comprising proton-pump inhibitor, bismuth,
      amoxicillin, and metronidazole in Korea.
AB  - BACKGROUND: The standard triple Helicobacter pylori regimen now shows
      unacceptably low treatment success in Korea. Administration of the concomitant
      therapy for 10 days, which has a high cure rate, is recommended as an alternative
      first-line treatment in areas of high clarithromycin resistance including Korea.
      Recently, modified bismuth-containing quadruple therapy with amoxicillin (PAM-B
      therapy) showed excellent results, regardless of dual clarithromycin and
      metronidazole resistance. This study compared the concomitant therapy with PAM-B
      therapy as a first-line treatment for H. pylori infection. METHOD: Subjects
      infected with H. pylori and naive to treatment were performed a head-to-head
      comparison between 10-day concomitant therapy [rabeprazole 20 mg, amoxicillin 1
      g, clarithromycin 500 mg, and metronidazole 500 mg twice daily] and 14-day PAM-B
      therapy [rabeprazole 20 mg, amoxicillin 1 g, metronidazole 750 mg, and
      tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily].
      Six weeks after treatment, H. pylori eradication was assessed. RESULTS: Two
      hundred and seventy subjects were randomized. Both regimens achieved high cure
      rates: 83.0% (112/135) and 88.1% (119/135) by the intention-to-treat analysis and
      95.5% (106/111) and 96.6% (114/118) by the per-protocol analysis, respectively.
      The intention-to-treat and per-protocol analyses revealed no statistically
      significant difference in the eradication rate (P = .299 and P = .743,
      respectively). Rates of adverse events were similar between groups (25.2% vs
      23.0%, P -value: .776) Adverse events, which resulted in poor compliance,
      occurred in six patients of each group, but there were no serious complications.
      CONCLUSIONS: PAM-B therapy is as effective as concomitant therapy for eradicating
      H. pylori with comparative safety. PAM-B therapy is regarded as a promising
      alternative to standard triple therapy for a first-line eradication in Korea.

PMID- 29369455
TI  - Development and validation of the Cholinergic Urticaria Quality-of-Life
      Questionnaire (CholU-QoL).
AB  - BACKGROUND: Cholinergic urticaria (CholU), a common form of chronic inducible
      urticaria, is characterized by itchy weals that occur in response to physical
      exercise or passive warming. CholU patients frequently exhibit a high burden of
      disease. As of yet, no specific instrument is available to assess their disease
      related quality-of-life (QoL) impairment. OBJECTIVE: The aim of this study was to
      develop and validate the first disease-specific QoL instrument for CholU
      patients, the Cholinergic Urticaria Quality-of-Life Questionnaire (CholU-QoL).
      METHODS: Using a combined approach of the literature search, semistructured
      patient interviews and expert opinion, we developed 96 potential CholU-QoL items.
      Subsequent item selection was performed by means of impact analysis complemented
      by an expert review for face validity. The resulting final CholU-QoL was then
      tested for levels of validity, reliability and influence factors in 88 CholU
      patients. In parallel, an US American-Canadian English version of the CholU-QoL
      was developed. RESULTS: The final 28-item CholU-QoL was found to have a 5-domain
      structure ("symptoms," "functional life," "social interaction," "therapy,"
      "emotions") with excellent internal consistency. The CholU-QoL also showed a
      valid total score, and good levels of convergent validity, known-groups validity,
      as well as test-retest reliability. Multiple regression analysis found no
      significant drivers of the CholU-QoL total score. CONCLUSIONS AND CLINICAL
      RELEVANCE: The CholU-QoL is the first disease-specific QoL instrument for CholU
      and also the first specific QoL measure in the field of chronic inducible
      urticarias. It may serve as a valuable tool for clinical trials and improve
      routine patient management.

PMID- 29369456
TI  - Assessment of efficacy and safety of eslicarbazepine acetate for the treatment of
      trigeminal neuralgia.
AB  - BACKGROUND: Antiepileptic drugs are the first-line treatment for trigeminal
      neuralgia (TN). Carbamazepine and oxcarbazepine are the most studied with well
      known efficacy. Eslicarbazepine acetate is a third-generation antiepileptic drug
      that has not previously been evaluated for the treatment of TN. We aim to assess
      the efficacy, tolerability and safety of eslicarbazepine for TN. DESIGN AND
      METHODS: Retrospective, open-label, multicentric, intention-to-treat study. We
      included patients older than 18 years who met the ICHD-3 beta diagnostic criteria
      for TN. We evaluated the variation of intensity and frequency of pain paroxysms
      before and after treatment with eslicarbazepine. Secondary objectives assessed
      were tolerability and safety of eslicarbazepine. RESULTS: Eighteen patients were
      included, 15 women, mean age 65.2 years old, mean follow-up 21.1 months. The mean
      number of drugs tested before eslicarbazepine was 2; 10 patients used
      eslicarbazepine as monotherapy. After the treatment with ESL, the median of pain
      intensity improved from 9.5 to 2.5 (p < 0.001) and the median of pain paroxysms
      frequency improved from 70 episodes per week to 0.37 (p < 0.001). Responder rate
      was 88.9%; 44.4% became asymptomatic after treatment. Sixty-one per cent of
      patients presented some adverse event; four patients discontinued eslicarbazepine
      for this reason. Despite this, 16 patients (88.9%) noticed a good subjective
      tolerance to eslicarbazepine. The retention rate at 6 months was 77.8% and at 12
      months 61.1%. CONCLUSIONS: Our study supports the hypothesis that eslicarbazepine
      acetate is an effective, safe and well-tolerated treatment for the treatment of
      TN. Further studies are warranted to corroborate these results. SIGNIFICANCE:
      Eslicarbazepine acetate has shown to be an effective, safe and well-tolerated
      drug for TN. This is the first study that evaluated the efficacy of this drug on
      TN in humans.

PMID- 29369457
TI  - The economic burden of epilepsy in Bhutan.
AB  - OBJECTIVE: To assess the economic impact of epilepsy in Bhutan, a lower-middle
      income country with a universal health care system, but with limited access to
      neurological care. METHODS: A cross-sectional survey was conducted of patients
      with epilepsy at the Jigme Dorji Wangchuk National Referral Hospital from January
      to August 2016. Data were collected on clinical features, cost of care, impact of
      epilepsy on school or work and household economic status of participants and
      matched comparisons (a sibling or neighbour from a household without epilepsy).
      RESULTS: A total of 172 individuals were included in the study (130 adults and 42
      children). One-third of adults and 20 (48%) children had seizures at least once
      per month. Mean direct out-of-pocket cost for epilepsy care was 6054 Bhutanese
      Ngultrum (BTN; 91 USD) per year, of which transportation formed the greatest
      portion (53%). Direct costs of epilepsy were an average of 3.2% of annual
      household income. Adults missed 6.8 (standard deviation [SD]: 9.0) days of work
      or school per year on average, and children missed 18.6 (SD: 34.7) days of
      school. Among adults, 23 (18%) abandoned employment or school because of
      epilepsy; seven children (18%) stopped school because of epilepsy. Households
      with a person with epilepsy had a lower monthly per-person income (6434 BTN) than
      comparison households without epilepsy (8892 BTN; P = 0.027). CONCLUSIONS: In
      Bhutan, despite universal health care services, households of people with
      epilepsy face a significant economic burden. With many adults and children unable
      to attend school or work, epilepsy causes a major disruption to individuals'
      livelihoods.

PMID- 29369458
TI  - Clinical reactivity of celery cultivars in allergic patients: Role of Api g 1.
AB  - BACKGROUND: Celery (Apium graveolens L.) is a vegetable consumed world-wide.
      Celery stalks and celeriac roots are often ingredients in convenient food
      products like spice blends and soups. OBJECTIVE: In this study, we examined the
      allergenicity of distinct celeriac cultivars. METHODS: Sixteen celery-allergic
      patients were identified using a double-blind, placebo-controlled food challenge.
      Ten different celeriac cultivars were used for skin prick testing in the
      patients. Two cultivars were further applied for oral food challenges; their
      protein composition was analysed by immunoblotting, and contents of major
      allergen Api g 1 were quantified. RESULTS: From the 10 investigated celeriac
      cultivars, two cultivars elicited significantly different skin reactivity
      ("Anita": 5.0 [2.0-12.0] mm vs "Prinz": 7.0 [3.0-9.5] mm; P = .047). Moreover,
      "Anita" induced fewer symptoms after a controlled oral-celeriac challenge in 14
      patient (P < .001). The protein profiles on 2DE protein gels showed distinct
      protein patterns and higher protein amounts of Api g 1 in "Prinz" than in
      "Anita." CONCLUSIONS AND CLINICAL RELEVANCE: Taken together, the data from this
      study suggest that cultivar Anita is better tolerated in celery-allergic patients
      than "Prinz." Differences in the protein expression profile between the
      cultivars, particularly the different content of Api g 1, could cause the
      different allergenicity.

PMID- 29369459
TI  - Breeding implications of drought stress under future climate for upland rice in
      Brazil.
AB  - Rice is the most important food crop in the developing world. For rice production
      systems to address the challenges of increasing demand and climate change,
      potential and on-farm yield increases must be increased. Breeding is one of the
      main strategies toward such aim. Here, we hypothesize that climatic and
      atmospheric changes for the upland rice growing period in central Brazil are
      likely to alter environment groupings and drought stress patterns by 2050,
      leading to changing breeding targets during the 21st century. As a result of
      changes in drought stress frequency and intensity, we found reductions in
      productivity in the range of 200-600 kg/ha (up to 20%) and reductions in yield
      stability throughout virtually the entire upland rice growing area (except for
      the southeast). In the face of these changes, our crop simulation analysis
      suggests that the current strategy of the breeding program, which aims at
      achieving wide adaptation, should be adjusted. Based on the results for current
      and future climates, a weighted selection strategy for the three environmental
      groups that characterize the region is suggested. For the highly favorable
      environment (HFE, 36%-41% growing area, depending on RCP), selection should be
      done under both stress-free and terminal stress conditions; for the favorable
      environment (FE, 27%-40%), selection should aim at testing under reproductive and
      terminal stress, and for the least favorable environment (LFE, 23%-27%),
      selection should be conducted for response to reproductive stress only and for
      the joint occurrence of reproductive and terminal stress. Even though there are
      differences in timing, it is noteworthy that stress levels are similar across
      environments, with 40%-60% of crop water demand unsatisfied. Efficient crop
      improvement targeted toward adaptive traits for drought tolerance will enhance
      upland rice crop system resilience under climate change.

PMID- 29369460
TI  - Fluoride-Catalyzed Esterification of Amides.
AB  - In recent years, it has been demonstrated that amide carbon-nitrogen bonds can be
      activated and selectively cleaved using transition metal catalysts. However,
      these methodologies have been restricted to specific amides; a one-to-one
      relationship exists between the catalytic system and the amides and also uses
      large amounts of transition-metal catalysts and ligands. Hence, we now report a
      general strategy for esterification of common amides using fluoride as a
      catalyst. This method shows high functional group tolerance, and notably it
      requires only a slight excess of the alcohol nucleophile, which is a rare case in
      transition-metal-free amide transformations. Moreover, this approach may provide
      a new understanding for further studies on esterification of amides and is
      expected to stimulate the development of alternative methods for direct
      functionalization of amides.

PMID- 29369462
TI  - Base-Free Generation of Organic Electron Donors from Air-Stable Precursors.
AB  - Organic electron donors (OEDs) are powerful reducing agents recognized for their
      potential in the reduction of challenging substrates and in original
      applications. Nonetheless, their low stability in atmospheric oxygen or over time
      complicates their manipulation and storage. To overcome these constraints and
      enhance OED practicality, new air- and moisture-stable aminopyridinium
      carboxylate and carbonate precursors were synthesized and thermally activated to
      generate the potent electron donor in situ. Carboxylate adducts proved to be
      excellent latent OED systems, enabling the facile and efficient reduction of
      challenging substrates. Their reduction properties were correlated to their
      structural characteristics by thermogravimetric and spectroscopic analysis.

PMID- 29369461
TI  - Modulation of AKR1C2 by curcumin decreases testosterone production in prostate
      cancer.
AB  - Intratumoral androgen biosynthesis has been recognized as an essential factor of
      castration-resistant prostate cancer. The present study investigated the effects
      of curcumin on the inhibition of intracrine androgen synthesis in prostate
      cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated
      with or without curcumin after which cell proliferation was measured at 0, 24, 48
      and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma
      of the mouse prostate (TRAMP) model were obtained after 1-month oral
      administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone
      concentrations in LNCaP prostate cancer cells were determined through LC-MS/MS
      assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate
      cancer cells in a dose-dependent manner. Curcumin decreased the expression of
      steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer
      cell lines, supporting the decrease of testosterone production. After 1-month
      oral administration of curcumin, Aldo-Keto reductase 1C2 (AKR1C2) expression was
      elevated. Simultaneously, decreased testosterone levels in the prostate tissues
      were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably
      increased the expression of AKR1C2 in prostate cancer cell lines, supporting the
      decrease of dihydrotestosterone. Taken together, these results suggest that
      curcumin's natural bioactive compounds could have potent anticancer properties
      due to suppression of androgen production, and this could have therapeutic
      effects on prostate cancer.

PMID- 29369464
TI  - Genome Mining of the Lipopeptide Biosynthesis of Paenibacillus polymyxa E681 in
      Combination with Mass Spectrometry: Discovery of the Lipoheptapeptide
      Paenilipoheptin.
AB  - Paenibacillus polymyxa strains are qualified for agro-biotechnological uses such
      as plant growth promotion and for biocontrol strategies against deleterious
      phytopathogenic competitors in the soil depending on their attractive arsenal of
      bioactive compounds. Moreover, they are potent producers of antibiotics for
      medical applications. To identify new products of such organisms, genome mining
      strategies in combination with mass spectrometry are the methods of choice.
      Herein, we performed such studies with the Paenibacillus strain E681.
      Bioinformatic evaluation of its genome sequence revealed four gene clusters A-D
      encoding nonribosomal peptide synthetases (NRPSs). Accordingly, four lipopeptide
      families were detected by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF MS). Clusters A and D codify the well known
      fusaricidins and polymyxins. A yet-unknown lipoheptapeptide was discovered and
      structurally characterized by de novo sequencing by using MALDI-LIFT-TOF/TOF MS.
      It was designated as paenilipoheptin. From structure predictions we infer that
      the production of this agent is encoded by gene cluster C. Gene cluster B encodes
      the synthesis of tridecaptins, a family of open-chain lipotridecapeptides. Strain
      E681 produces new subspecies of such compounds (tridecaptins E) showing
      variations both in their fatty-acid part as well as in their peptide part.

PMID- 29369465
TI  - Bevacizumab and Bleomycin combination for treatment of orbital lymphatico-venous
      malformation recalcitrant to sclerosing therapy alone.

PMID- 29369463
TI  - Evaluation of the accuracy and clinical practicality of a calculation system for
      patient positional displacement in carbon ion radiotherapy at five sites.
AB  - PURPOSE: We developed a system for calculating patient positional displacement
      between digital radiography images (DRs) and digitally reconstructed radiography
      images (DRRs) to reduce patient radiation exposure, minimize individual
      differences between radiological technologists in patient positioning, and
      decrease positioning time. The accuracy of this system at five sites was
      evaluated with clinical data from cancer patients. The dependence of calculation
      accuracy on the size of the region of interest (ROI) and initial position was
      evaluated for clinical use. METHODS: For a preliminary verification, treatment
      planning and positioning data from eight setup patterns using a head and neck
      phantom were evaluated. Following this, data from 50 patients with prostate,
      lung, head and neck, liver, or pancreatic cancer (n = 10 each) were evaluated.
      Root mean square errors (RMSEs) between the results calculated by our system and
      the reference positions were assessed. The reference positions were manually
      determined by two radiological technologists to best-matching positions with
      orthogonal DRs and DRRs in six axial directions. The ROI size dependence was
      evaluated by comparing RMSEs for three different ROI sizes. Additionally,
      dependence on initial position parameters was evaluated by comparing RMSEs for
      four position patterns. RESULTS: For the phantom study, the average (+/- standard
      deviation) translation error was 0.17 +/- 0.05, rotation error was 0.17 +/- 0.07,
      and DeltaD was 0.14 +/- 0.05. Using the optimal ROI size for each patient site,
      all cases of prostate, lung, and head and neck cancer with initial position
      parameters of 10 mm or under were acceptable in our tolerance. However, only four
      liver cancer cases and three pancreatic cancer cases were acceptable, because of
      low-reproducibility regions in the ROIs. CONCLUSION: Our system has clinical
      practicality for prostate, lung, and head and neck cancer cases. Additionally,
      our findings suggest ROI size dependence in some cases.

PMID- 29369466
TI  - Luminescent thermometer based on Eu3+ /Tb3+ -organic-functionalized mesoporous
      silica.
AB  - In this work we investigate a mesoporous silica (MS) decorated with dipyridyl
      pyridazine (dppz) ligands and further grafted with a mixture of Eu3+ /Tb3+ ions
      (28.45%:71.55%), which was investigated as a potential thermometer in the 10-360
      K temperature range. The MS material was prepared employing a hetero Diels-Alder
      reaction: 3,6-di(2-pyridyl)-1,2,4,5-tetrazine was reacted with the double bonds
      of vinyl-silica (vSilica) followed by an oxidation procedure. We explore using
      the dppz-vSilica material to obtain visible emitting luminescent materials and
      for obtaining a luminescent thermometer when grafted with Eu3+ /Tb3+ ions. For
      the dppz-vSilica@Eu,Tb material absolute sensitivity Sa of 0.011 K-1 (210 K) and
      relative sensitivity Sr of 1.32 %K-1 (260 K) were calculated showing good sensing
      capability of the material. Upon temperature change from 10 K to 360 K the
      emission color of the material changed gradually from yellow to red.

PMID- 29369468
TI  - Temporally stable frequency mapping using continuous wavelet transform analysis
      in patients with persistent atrial fibrillation.
AB  - INTRODUCTION: Dominant frequency (DF) derived from fast Fourier transform (FFT)
      analysis has failed to guide atrial fibrillation (AF) ablation since it cannot
      guarantee temporal stability. Continuous wavelet transform (CWT) analysis is
      another frequency analysis that can show the temporal stability of a frequency.
      METHODS AND RESULTS: Forty-four consecutive patients with persistent AF (PeAF)
      underwent pulmonary vein (PV) isolation (PVI) as the first-time catheter
      ablation. The PVs and left atrium were mapped and electrograms (EGMs) were
      recorded for 30 seconds at each site. Pseudo-frequency (PF) and coefficient of
      variation (CV) were calculated by CWT analysis. A PF with CV <= 10 was defined as
      a temporally stable PF (sPF). DF was also calculated by traditional FFT analysis
      from the first 5 seconds of the recorded EGMs. The highest sPF was shown inside
      the PVs in 20 patients (PV group), and at the non-PV sites in 24 patients (non-PV
      group). During the follow-up period of 15.3 +/- 4.4 months, the ablation success
      rate in the PV group was significantly higher than that in the non-PV group (90%
      vs. 62%, P = 0.023). The location of the highest DF did not have a significant
      effect on ablation success rate between inside the PVs and at the non-PV sites.
      CONCLUSION: PVI results for PeAF were significantly worse for patients with
      highest sPF at the non-PV sites compared to patients with highest sPF sites
      inside the PVs. CWT analysis during AF could be used to verify whether PVI alone
      is sufficient for the first-time catheter ablation in patients with PeAF.

PMID- 29369467
TI  - Understanding hepatitis C intervention success-Qualitative findings from the
      HepCATT study.
AB  - The United Kingdom has committed to eliminating viral hepatitis as a public
      health threat. Innovative interventions for marginalized populations are required
      to realize this goal. In 2016, the HepCATT study team implemented a complex
      hepatitis C (HCV) intervention in three English drug treatment services, with
      five controls. We report qualitative study findings from two intervention sites
      to explore intervention success and transferability potential. The intervention
      comprised multiple components, including a nurse facilitator, peer support and
      education initiatives. Qualitative data were generated at baseline (2014) and
      post-intervention (2016) at two sites through in-depth interviews, focus groups
      and observations. The 96 participants comprised drug service and intervention
      providers and clients with an injecting history. Data were triangulated and
      thematically analysed. Client engagement with a HCV treatment service rose from
      16 at baseline to 147 in 2016. There was no comparable increase at the five
      control sites. Baseline testing and treatment barriers included the following:
      limited HCV knowledge; fear of diagnosis and treatment; precarious living
      circumstances and service-specific obstacles. Treatment engagement was aided by
      intervention timeliness; improved communication structures; personalized care;
      streamlined testing and treatment pathways; peer support. Multiple interrelated
      components influenced the increased levels of treatment engagement documented in
      HepCATT. The nurse facilitator, involved in implementation and innovation, was
      key to intervention success. Baseline barriers correspond with international
      literature-indicating transferability potential. Control data indicate that
      biomedical innovation alone is not sufficient to increase engagement among the
      most marginalized. Sustainable resourcing of community services is crucial to
      effect change.

PMID- 29369469
TI  - Crassulacean acid metabolism in the Basellaceae (Caryophyllales).
AB  - C4 and crassulacean acid metabolism (CAM) have evolved in the order
      Caryophyllales many times but neither C4 nor CAM have been recorded for the
      Basellaceae, a small family in the CAM-rich sub-order Portulacineae. 24 h gas
      exchange and day-night changes in titratable acidity were measured in leaves of
      Anredera baselloides exposed to wet-dry-wet cycles. While net CO2 uptake was
      restricted to the light period in well-watered plants, net CO2 fixation in the
      dark, accompanied by significant nocturnal increases in leaf acidity, developed
      in droughted plants. Plants reverted to solely C3 photosynthesis upon rewatering.
      The reversible induction of nocturnal net CO2 uptake by drought stress indicates
      that this species is able to exhibit CAM in a facultative manner. This is the
      first report of CAM in a member of the Basellaceae.

PMID- 29369470
TI  - Hypothermic oxygenated machine perfusion reduces bile duct reperfusion injury
      after transplantation of donation after circulatory death livers.
AB  - Dual hypothermic oxygenated machine perfusion (DHOPE) of the liver has been
      advocated as a method to reduce ischemia/reperfusion injury (IRI). This study
      aimed to determine whether DHOPE reduces IRI of the bile ducts in donation after
      circulatory death (DCD) liver transplantation. In a recently performed phase 1
      trial, 10 DCD livers were preserved with DHOPE after static cold storage (SCS;
      www.trialregister.nl NTR4493). Bile duct biopsies were obtained at the end of SCS
      (before DHOPE; baseline) and after graft reperfusion in the recipient.
      Histological severity of biliary injury was graded according to an established
      semiquantitative grading system. Twenty liver transplantations using DCD livers
      not preserved with DHOPE served as controls. Baseline characteristics and the
      degree of bile duct injury at baseline (end of SCS) were similar between both
      groups. In controls, the degree of stroma necrosis (P = 0.002) and injury of the
      deep peribiliary glands (PBG; P = 0.02) increased after reperfusion compared with
      baseline. In contrast, in DHOPE-preserved livers, the degree of bile duct injury
      did not increase after reperfusion. Moreover, there was less injury of deep PBG
      (P = 0.04) after reperfusion in the DHOPE group compared with controls. In
      conclusion, this study suggests that DHOPE reduces IRI of bile ducts after DCD
      liver transplantation. Liver Transplantation 24 655-664 2018 AASLD.

PMID- 29369471
TI  - Management of pregnancy complicated with intracranial arteriovenous malformation.
AB  - AIM: To clarify the perinatal outcomes in pregnancy complicated with intracranial
      arteriovenous malformation (i-AVM). METHODS: A retrospective study was performed
      in 36 pregnancies complicated by i-AVM from 1981 to 2013 at one institution.
      RESULTS: In total, 6 women miscarried, and 30 had live births. The median (range)
      gestational age at delivery was 38 (24-40) weeks; 11 cases experienced initial i
      AVM rupture during pregnancy (first, second and third trimester: 18%, 64% and
      18%, respectively). At onset, 4 cases had a Glasgow Coma Scale <=10, 10 cases
      needed emergency maternal transport, 4 underwent neurosurgery with the fetus in
      utero and 4 had termination of pregnancy in the second trimester for emergent
      treatment for i-AVM. Two cases delivered vaginally. Another 25 cases had already
      been diagnosed as i-AVM at conception. Of these, as an indication for epidural
      birth, 18 cases had either residual lesion of i-AVM or neurological symptoms,
      although 18 cases had received treatments of i-AVM before conception. Without
      rupture of i-AVM and worsening of symptoms, 15 cases succeeded in epidural birth.
      One case was delivered by cesarean section for residual i-AVM with indication of
      treatment. Another case who had refused treatment of i-AVM experienced rupture of
      i-AVM 1 year after delivery. CONCLUSION: Most of the cases with residual i-AVM
      lesion and neurological symptoms could deliver vaginally without worsening of
      symptoms. However, pregnancy with i-AVM can be complicated by rupture of i-AVM.
      In cases with a residual lesion with indication of treatment and rupture of i-AVM
      during pregnancy, meticulous care is required during pregnancy and after
      delivery.

PMID- 29369472
TI  - Evaluation of autophagy induction on HEV 239 vaccine immune response in a mouse
      model.
AB  - Hepatitis E virus (HEV) infection remains a serious threat to life and
      productivity in developing world. Vaccine seems to be an effective, safe, and
      affordable approach to address HEV disease burden. The HEV genome consists of
      three open reading frames (ORFs). Of these, ORF2 encodes a single structural
      protein (pORF2) for the HEV capsid which has been studied extensively as vaccine
      candidates. Recently, it has been recognized that autophagy plays an important
      role in innate and adaptive immunity defense against intracellular pathogens.
      This mechanism could therefore promote a protective immune response by inducing
      CD4+ and CD8+ T cells. In this study, HEV 239 and Beclin1 proteins were expressed
      in prokaryotic host cell [Escherichia coli (BL21)]. HEV 239 protein with
      different formulations (+Alum, +Beclin1, and +Alum-Beclin1) were used as
      candidate vaccines and administrated subcutaneously in BALB/c mice on 0, 14, and
      28 days. Finally, elicited cellular and humoral immunity were evaluated. Taken
      together, although our results indicated that mice immunized with HEV 239 protein
      formulated with Alum, Beclin1, and Alum + Beclin1 displayed humoral and cellular
      response that was not significant in comparison with each other (P > 0.05);
      whereas they were significant while compared with control groups (P < 0.05). A
      comprehensive understanding of the intricate interplay between autophagy and
      immune response remains to be unraveled. Further study will clear the detailed
      impact of autophagy manipulation to enhance vaccine efficacy and boost the immune
      responses against the disease. (c) 2018 IUBMB Life, 70(3):207-214, 2018.

PMID- 29369473
TI  - Comparative pharmacology and toxicology of tramadol and tapentadol.
AB  - : Moderate-to-severe pain represents a heavy burden in patients' quality of life,
      and ultimately in the society and in healthcare costs. The aim of this review was
      to summarize data on tramadol and tapentadol adverse effects, toxicity, potential
      advantages and limitations according to the context of clinical use. We compared
      data on the pharmacological and toxicological profiles of tramadol and
      tapentadol, after an extensive literature search in the US National Library of
      Medicine (PubMed). Tramadol is a prodrug that acts through noradrenaline and
      serotonin reuptake inhibition, with a weak opioid component added by its
      metabolite O-desmethyltramadol. Tapentadol does not require metabolic activation
      and acts mainly through noradrenaline reuptake inhibition and has a strong opioid
      activity. Such features confer tapentadol potential advantages, namely lower
      serotonergic, dependence and abuse potential, more linear pharmacokinetics,
      greater gastrointestinal tolerability and applicability in the treatment of
      chronic and neuropathic pain. Although more studies are needed to provide clear
      guidance on the opioid of choice, tapentadol shows some advantages, as it does
      not require CYP450 system activation and has minimal serotonergic effects. In
      addition, it leads to less side effects and lower abuse liability. However, in
      vivo and in vitro studies have shown that tramadol and tapentadol cause similar
      toxicological damage. In this context, it is important to underline that the
      choice of opioid should be individually balanced and a tailored decision, based
      on previous experience and on the patient's profile, type of pain and context of
      treatment. SIGNIFICANCE: This review underlines the need for a careful
      prescription of tramadol and tapentadol. Although both are widely prescribed
      synthetic opioid analgesics, their toxic effects and potential dependence are not
      completely understood yet. In particular, concerning tapentadol, further research
      is needed to better assess its toxic effects.

PMID- 29369474
TI  - Reversible Dihydrogen Activation and Hydride Transfer by a Uranium Nitride
      Complex.
AB  - Cleavage of dihydrogen is an important step in the industrial and enzymatic
      transformation of N2 into ammonia. The reversible cleavage of dihydrogen was
      achieved under mild conditions (room temperature and 1 atmosphere of H2 ) by the
      molecular uranium nitride complex, [Cs{U(OSi(Ot Bu)3 )3 }2 (MU-N)] 1, leading to
      a rare hydride-imide bridged diuranium(IV) complex, [Cs{U(OSi(Ot Bu)3 )3 }2 (MU
      H)(MU-NH)], 2 that slowly releases H2 under vacuum. This complex is highly
      reactive and quickly transfers hydride to acetonitrile and carbon dioxide at room
      temperature, affording the ketimide- and formate-bridged UIV species [Cs{U(OSi(Ot
      Bu)3 )3 }2 (MU-NH)(MU-CH3 CHN)], 3 and [Cs{U(OSi(Ot Bu)3 )3 }2 (MU-HCOO)(MU
      NHCOO)], 4.

PMID- 29369475
TI  - Do fertile women have an inferior treatment for high-grade precancerous lesions?
AB  - AIM: To investigate whether a concern for future pregnancy is reflected in the
      extent of large loop excision of the transformation zone (LLETZ) and to assess
      the clinical outcome. METHODS: We reviewed the medical records of 275 women who
      underwent LLETZ for precancerous lesions in cervix. We divided them into two
      groups according to pregnancy possibility in the future: nonpotential versus
      potential group. The potential group was arbitrarily defined as women who met one
      of the following: (i) regardless of marital status, younger than 41 years with
      less than two parities and (ii) regardless of parity, younger than 46 years and
      unmarried. After propensity score matching (1:1, 44 women in each group), we
      compared the extent of LLETZ with respect to short-term recurrence. RESULTS:
      After LLETZ, similar percentages of patients were finally diagnosed with >=CIN3
      (cervical intraepithelial neoplasia 3) in the two groups (27 [61.4%] vs 32
      [72.7%], P = 0.257). Notably, the largest transverse diameter of LLETZ specimen
      was significantly larger in the nonpotential group (2.74 +/- 1.06 vs 2.37 +/-
      0.62 cm, P = 0.047). There were more women with exocervical resection margin
      involvement in the potential group than in the nonpotential group (14 [31.8%] vs
      6 [13.6%], P = 0.042). However, there was no significant difference in the
      incidence of short-term recurrence >=HSIL (high-grade squamous intraepithelial
      lesion) within 24 months after LLETZ between the two groups (1 [2.3%] vs 1
      [2.3%], P > 0.999). CONCLUSION: Pregnancy possibility in the future may affect
      the extent of LLETZ, as assessed by the largest transverse diameter obtained.
      This finding may be associated with increased resection margin involvement in
      women with future pregnancy possibility.

PMID- 29369476
TI  - Platelets contribute to the initiation of colitis-associated cancer by promoting
      immunosuppression.
AB  - : Essentials Inflammation plays a key role in the development of colorectal
      cancer. Understanding mechanisms of cancer initiation might reveal new anticancer
      preventive strategy. Hyperactive platelets promote tumor formation by fostering
      immune evasion of cancer. Platelet inhibition by clopidogrel prevents
      carcinogenesis by restoring antitumor immunity. SUMMARY: Background Clinical and
      experimental evidence support a role for inflammation in the development of
      colorectal cancer, although the mechanisms are not fully understood. Beyond
      thrombosis and hemostasis, platelets are key actors in inflammation; they have
      also been shown to be involved in cancer. However, whether platelets participate
      in the link between inflammation and cancer is unknown. Objective To investigate
      the contribution of platelets and platelet-derived proteins to inflammation
      elicited colorectal tumor development. Methods We used a clinically relevant
      mouse model of colitis-associated cancer. Platelet secretion and platelet
      reactivity to thrombin were assessed at each stage of carcinogenesis. We
      conducted an unbiased proteomic analysis of releasates of platelets isolated at
      the pretumoral stage to identify soluble factors that might act on tumor
      development. Plasma levels of the identified proteins were measured during the
      course of carcinogenesis. We then treated the mice with clopidogrel to
      efficiently inhibit platelet release reaction. Results At the pretumoral stage,
      hyperactive platelets constituted a major source of circulating protumoral serum
      amyloid A (SAA) proteins. Clopidogrel prevented the early elevation of the plasma
      SAA protein level, decreased colitis severity, and delayed the formation of
      dysplastic lesions and adenocarcinoma. Platelet inhibition hindered the expansion
      and function of immunosuppressive myeloid cells, as well as their infiltration
      into tumors, but increased the number of tissue CD8+ T cells. Platelets and
      releasates of platelets from mice with cancer were both able to polarize myeloid
      cells towards an immunosuppressive phenotype. Conclusions Thus, platelets promote
      the initiation of colitis-associated cancer by enhancing myeloid cell-dependent
      immunosuppression. Antiplatelet agents may help to prevent inflammation-elicited
      carcinogenesis by restoring antitumor immunity.

PMID- 29369477
TI  - Retinopathy of prematurity: the high cost of screening regional and remote
      infants.
AB  - IMPORTANCE: Demand for retinopathy of prematurity (ROP) screening is increasing
      for infants born at rural and regional hospitals where the service is not
      generally available. The health system cost for screening regional/remote infants
      has not been reported. BACKGROUND: The objective of this study is to evaluate the
      cost of ROP screening at a large centralized tertiary neonatal service for
      infants from regional/rural hospitals. DESIGN: This is a retrospective study to
      establish the cost of transferring regional/rural infants to the Royal Brisbane
      and Women's Hospital for ROP screening over a 28-month period. PARTICIPANTS: A
      total of 131 infants were included in this study. METHODS: Individual infant
      costs were calculated from analysis of clinical and administrative records. MAIN
      OUTCOME MEASURES: Economic cost of ROP screening for all transfers from
      regional/rural hospitals to Royal Brisbane and Women's Hospital. RESULTS: The
      average economic cost of ROP screening for this cohort was AUD$5110 per infant
      screened and the total cost was AUD$669 413. The average cost per infant screened
      was highest for infants from a regional centre with a population of 75 000
      (AUD$14 856 per child), which was also geographically furthest from Brisbane. No
      infant in this cohort transferred from a regional nursery reached criteria for
      intervention for ROP by standard guidelines. CONCLUSIONS AND RELEVANCE: Health
      system costs for ROP screening of remote infants at a centralized hospital are
      high. Alternative strategies using telemedicine can now be compared with
      centralized screening.

PMID- 29369478
TI  - Pregnancy-Associated Stroke.
AB  - Cerebrovascular accident, or stroke, is the fourth leading cause of death for all
      women and the eighth leading cause of pregnancy-associated death. The physiologic
      changes of pregnancy increase the risk of cerebrovascular accident for women.
      With current incidence rates, a facility with 3300 births per year can anticipate
      caring for one woman with a pregnancy-related stroke at least every 2 years. All
      maternity care providers must be able to assess women experiencing stroke-like
      symptoms and initiate timely care to mitigate brain tissue damage, decrease long
      term morbidity, and prevent mortality. The 2 main types of stroke, ischemic and
      hemorrhagic, have similar presenting symptoms but very different pathophysiology
      and treatment. This article reviews assessment and initial treatment of pregnant
      and postpartum women experiencing stroke and provides guidance for subsequent
      maternity and primary care to assist front-line perinatal care providers who may
      be the first to treat affected women or may resume primary care after diagnosis.

PMID- 29369479
TI  - Chitosan-Based Thermo/pH Double Sensitive Hydrogel for Controlled Drug Delivery.
AB  - A series of thermo/pH sensitive N-succinyl hydroxybutyl chitosan (NSHBC)
      hydrogels with different substitution degrees of succinyl are prepared for drug
      delivery. Rheology analysis shows that the gelation temperature of NSHBC
      hydrogels is 3.8  degrees C higher than that of hydroxybutyl chitosan (HBC)
      hydrogels. A model drug bovine serum albumin (BSA) is successfully loaded and
      released. NSHBC hydrogels show excellent pH sensitivity drug release behaviors.
      After incubation for 24 h, 93.7% of BSA is released from NSHBC hydrogels in
      phosphate buffer saline (PBS) (pH 7.4), which is significantly greater than that
      of 24.6% at pH 3.0. In contrast, the release rate of BSA from HBC is about 70.0%
      at pH 3.0 and 7.4. Thus, these novel hydrogels have the prominent merits of high
      adaptability to soluble drugs and pH sensitivity triggered release, indicating
      that NSHBC hydrogels have promising applications in oral drug delivery.

PMID- 29369480
TI  - Retrospective analysis of HDFN due to ABO incompatibility in a single institution
      over 6 years.
AB  - OBJECTIVES: To study the rate of ABO haemolytic anaemia of fetus and newborn
      (HDFN) in one institution over 6 years. BACKGROUND: ABO major incompatibility
      between mothers and their newborns occurs in about 10% of births. So, mothers
      with an O blood group may form IgG-class antibodies against A and B antigens,
      which could pass across the placenta and lead to a variable degree of HDFN in the
      newborn. METHODS: At our institution, we have reviewed data regarding ABO-based
      HDFN in the last 6 years. RESULTS: We found that, in 28 089 deliveries, an ABO
      major incompatibility between mothers and newborns occurs in 11% of cases, with
      72% of O/A and 28% of O/B incompatibility. In turn, 23% of these newborns had an
      eluate-confirmed positive direct antiglobulin test [DAT; 74% (511) were due to
      anti-A and 26% (179) to anti-B], with 1.0% requiring invasive treatments
      (exchange transfusion or intravenous immunoglobulin). Overall, 2.5% of the total
      newborns had a positive DAT for an anti-A or anti-B antibody, and 0.11% required
      invasive treatment in addition to phototherapy for their HDFN. CONCLUSIONS:
      Serological ABO HDFN is a relatively frequent event when an O-A/O-B
      incompatibility between mothers and their newborn occurs and, in most cases,
      translates into a self-limiting disease, with a small number of newborns
      requiring invasive treatments. The DAT test, although not predictive of disease
      severity, appears to be a useful tool to monitor babies born from O-A/O-B
      incompatible pregnancies and to identify those who may require treatment.

PMID- 29369481
TI  - RBBP6 increases radioresistance and serves as a therapeutic target for
      preoperative radiotherapy in colorectal cancer.
AB  - Radiotherapy (RT) can be used as preoperative treatment to downstage initially
      unresectable locally rectal carcinoma, but radioresistance and recurrence remain
      significant problems. Retinoblastoma binding protein 6 (RBBP6) has been
      implicated in the regulation of cell cycle, apoptosis and chemoresistance both in
      vitro and in vivo. The present study investigated whether the inhibition of RBBP6
      expression would improve radiosensitivity in human colorectal cancer cells. After
      SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and
      protein increased over time in both cells. Moreover, a significant reduction in
      clonogenic survival and a decrease in cell viability in parallel with an obvious
      increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells.
      Transfection with RBBP6 shRNA improved the levels of G2-M phase arrest, which
      blocked the cells in a more radiosensitive period of the cell cycle. These
      observations indicated that cell cycle and apoptosis mechanisms may be connected
      with tumor cell survival following radiotherapy. In vivo, the tumor growth rate
      of nude mice in the RBBP6-knockdown group was significantly slower than that in
      other groups. These results indicated that RBBP6 overexpression could resist
      colorectal cancer cells against radiation by regulating cell cycle and apoptosis
      pathways, and inhibition of RBBP6 could enhance radiosensitivity of human
      colorectal cancer.

PMID- 29369482
TI  - Norcantharidin, a clinical used chemotherapeutic agent, acts as a powerful
      inhibitor by interfering with fibrinogen-integrin alphaIIb beta3 binding in human
      platelets.
AB  - During platelet activation, fibrinogen binds to its specific platelet receptor,
      integrin alphaIIb beta3 , thus completing the final common pathway for platelet
      aggregation. Norcantharidin (NCTD) is a promising anticancer agent in China from
      medicinal insect blister beetle. In this study, we provided the evidence to
      demonstrate NCTD (0.1-1.0 MUM) possesses very powerful antiplatelet activity in
      human platelets; nevertheless, it had no effects on surface P-selectin expression
      and only slight inhibition on ATP-release reaction in activated platelets.
      Moreover, NCTD markedly hindered integrin alphaIIb beta3 activation by
      interfering with the binding of FITC-labelled PAC-1. It also markedly reduced the
      number of adherent platelets and the single platelet spreading area on
      immobilized fibrinogen as well as clot retraction. Additionally, NCTD attenuated
      phosphorylation of proteins such as integrin beta3 , Src and FAK in platelets
      spreading on immobilized fibrinogen. These results indicate that NCTD restricts
      integrin alphaIIb beta3 -mediated outside-in signalling in human platelets.
      Besides, NCTD substantially prolonged the closure time in human whole blood and
      increased the occlusion time of thrombotic platelet plug formation and prolonged
      the bleeding time in mice. In conclusion, NCTD has dual activities, it can be a
      chemotherapeutic agent for cancer treatment, and the other side it possesses
      powerful antiplatelet activity for treating thromboembolic disorders.

PMID- 29369483
TI  - Eudesmanolides and Other Constituents from the Flowers of Wedelia trilobata.
AB  - Two eudesmane sesquiterpene lactones, wedetrilides B (1) and C (2), along with
      five known analogues (3 - 8), an ent-kaurane diterpenoid (9), a steroid (10), as
      well as cinnamic acid derivatives (11 - 13), were isolated from the flowers of
      Wedelia trilobata. Their structures were elucidated on the basis of extensive
      spectroscopic analyses and by comparison of their NMR data with those of related
      compounds. Furthermore, the structures of 1 and 3 - 5 were confirmed by X-ray
      single-crystal diffraction analyses. Compounds 4 and 5 exhibited weak cytotoxic
      activities against the MCF-7, HeLa, and A549 cell lines. Compounds 3 - 5 were
      also evaluated for their inhibitory effects against HIV lytic replication.

PMID- 29369484
TI  - Characteristics and management of ganglioneuroma and ganglioneuroblastoma
      intermixed in children and adolescents.
AB  - BACKGROUND: Ganglioneuromas (GNs) usually demonstrate favorable histological and
      clinical features. Surgery is often performed due to clinical symptoms and/or
      theoretical concerns that GN may transform into neuroblastoma (NB); however,
      several studies have identified significant GN-surgical morbidities. OBJECTIVES:
      We compared the natural history, biological and clinical features of GN and
      ganglioneuroblastoma-intermixed (GNB-I) managed by surgery or observation to
      inform management and surveillance. PROCEDURES: This retrospective study includes
      patients (n = 67) with histological diagnosis of GN (50/67) and GNB-I (17/67) at
      the Hospital for Sick Children between 1990 and 2014. Clinical, pathological
      features, tumor dimensions, and management were recorded. RESULTS: Median age and
      maximal tumor diameter were 6 years (1.3-17.8) and 6.3 cm (1.4-16.9),
      respectively. Of the 67 patients, 46 (69%) had upfront surgery and 21 (31%) were
      observed. Of the 21 observed patients 4 later underwent resection. There were
      post-operative complications in 15 of the 50 (30%) surgical patients. The
      presence of imaging-defined risk factors correlated with complications (P =
      0.005). Observed patients were older (median 8.4 vs. 5.3 years) and diagnosed
      more recently. Median growth was 0.3 cm/year and 6 of 21 had progressive disease
      (PD). At median follow-up of 2.2 years (0.2-14.3), all patients were alive and
      for those with evaluable imaging there were 27 complete and 10 partial responses,
      19 stable and 6 PD. Pathology classification changed at resection for three
      cases, but no GN was reclassified to NB. CONCLUSIONS: GN and GNB-I have a slow
      growth rate and resection can be associated with significant morbidity. Watch and
      wait approaches should be considered for some GN and GNB-I.

PMID- 29369485
TI  - Sources of parental hope in pediatric oncology.
AB  - BACKGROUND: Hope is a multidimensional concept that is important for all parents
      of children with cancer. However, most work has focused on advanced cancer and
      poor prognoses. We examined hopes of all parents of children with cancer
      longitudinally during the first year of treatment. PROCEDURE: Prospective,
      longitudinal, questionnaire-based cohort study of parents and physicians of
      children with cancer at two academic pediatric hospitals. Parents reported on
      general sense of hopefulness and specific hopes at time of diagnosis (N = 374); a
      subset of parents (N = 164) were followed longitudinally at 4 and 12 months.
      RESULTS: Fifty-five percent of parents (N = 206/374) reported being extremely
      hopeful in general at baseline. Hopefulness did not significantly change over
      time, and most parents (51-58%) reported being extremely hopeful regardless of
      prognosis (P = 0.66). Most parents (N = 327/356) considered hope for cure to be
      an extremely important source of hope; most also reported hope that the child
      would feel loved (N = 328/356), that the child would have the best possible
      quality of life (N = 316/356), and that they would always do all they could for
      the child (N = 300/356). Hope for cure was slightly lower among parents of
      children with less than a 50% chance of cure at baseline (N = 53/63) when
      compared to those with better prognoses (moderately likely cure, N = 76/78; very
      likely cure, N = 198/215) (P = 0.02). CONCLUSIONS: Many hopes contribute to
      parental hopefulness, not just hope for cure. This hopefulness persists over
      time, even when the prognosis is poor. Clinicians should focus on supporting the
      myriad hopes that contribute to overall hopefulness.

PMID- 29369486
TI  - Utilization trends and safety of intravenous iron replacement in pediatric
      specialty care: A large retrospective cohort study.
AB  - BACKGROUND: Iron deficiency is a common and clinically diverse hematologic
      disorder in childhood for which oral iron is often an infeasible or ineffective
      treatment option. Intravenous (IV) iron can be an efficient and highly successful
      means of iron replacement but its use has not been well-characterized on a large
      scale in pediatrics. PROCEDURE: All IV iron doses administered to patients for
      iron replacement therapy at a tertiary pediatric hospital from January 2010
      through October 2016 were evaluated. Analyses included patient demographics,
      underlying medical conditions, and detailed information for each dose. Individual
      chart review was performed to identify infusion-related reactions. Nephrology
      patients as well as those patients 21 years or older at the time of the first
      infusion were excluded. RESULTS: A total of 1,088 doses of IV iron administered
      to 194 patients met inclusion criteria. A wide variety of specialties prescribed
      IV iron, with gastroenterology, hematology, and hospital medicine being the
      highest users in this cohort. A majority of patients (68%) required multiple
      infusions and dosing was highly variable, ranging from 1.3-1,030 mg per infusion.
      Premedication use was infrequent (10.3% of doses) and no severe infusion
      associated reactions occurred. CONCLUSIONS: IV iron is commonly prescribed by
      certain pediatric specialties but there is little standardization in the
      indications, formulations, or dosing. These data suggest that IV iron should be
      considered a safe alternative for iron deficiency treatment in pediatrics when
      oral iron is either unsuccessful or contraindicated.

PMID- 29369487
TI  - An update on adjunctive treatment options for bipolar disorder.
AB  - OBJECTIVES: Bipolar disorder is a complex illness often requiring combinations of
      therapies to successfully treat symptoms. In recent years, there have been
      significant advancements in a number of therapies for bipolar disorder. It is
      therefore timely to provide an overview of current adjunctive therapeutic options
      to help treating clinicians to inform their patients and work towards optimal
      outcomes. METHODS: Publications were identified from PubMed searches on bipolar
      disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation,
      interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e
      Health and brain stimulation techniques. Relevant articles in these areas were
      selected for further review. This paper provides a narrative review of adjunctive
      treatment options and is not a systematic review of the literature. RESULTS: A
      number of pharmacotherapeutic, psychological and neuromodulation treatment
      options are available. These have varying efficacy but all have shown benefit to
      people with bipolar disorder. Due to the complex nature of treating the disorder,
      combination treatments are often required. Adjunctive treatments to traditional
      pharmacological and psychological therapies are proving useful in closing the gap
      between initial symptom remission and full functional recovery. CONCLUSIONS:
      Given that response to monotherapy is often inadequate, combination regimens for
      bipolar disorder are typical. Correspondingly, psychiatric research is working
      towards a better understanding of the disorder's underlying biology. Therefore,
      treatment options are changing and adjunctive therapies are being increasingly
      recognized as providing significant tools to improve patient outcomes. Towards
      this end, this paper provides an overview of novel treatments that may improve
      clinical outcomes for people with bipolar disorder.

PMID- 29369489
TI  - Reply to: Comment on: Successful use of nitrous oxide during lumbar punctures: A
      call for nitrous oxide in pediatric oncology clinics.

PMID- 29369488
TI  - Transient elastography for non-invasive evaluation of post-transplant liver graft
      fibrosis in children.
AB  - As graft survival in pediatric LT is often affected by progressive fibrosis,
      numerous centers carry out protocol liver biopsies. Follow-up biopsy protocols
      differ from center to center, but all biopsies are progressively spaced out, as
      time from transplant increases. Therefore, there is a need for non-invasive
      techniques to evaluate graft fibrosis progression in those children who have no
      clinical or serological signs of liver damage. Indirect markers, such as the
      APRI, should be relied on with caution because their sensitivity in predicting
      fibrosis can be strongly influenced by the etiology of liver disease, severity of
      fibrosis, and patient age. A valid alternative could be TE, a non-invasive
      technique already validated in adults, which estimates the stiffness of the
      cylindrical volume of liver tissue, 100-fold the size of a standard needle biopsy
      sample. The aims of this study were to evaluate the reliability of TE in children
      after LT and to compare both the TE and the APRI index results with the
      histological scores of fibrosis on liver biopsies. A total of 36 pediatric LT
      recipients were studied. All patients underwent both TE and biopsy within a year
      (median interval -0.012 months) at an interval from LT of 0.36 to 19.47 years
      (median 3.02 years). Fibrosis was assessed on the biopsy specimens at histology
      and staged according to METAVIR. There was a statistically significant
      correlation between TE stiffness values and METAVIR scores (P = .005). The
      diagnostic accuracy of TE for the diagnosis of significant fibrosis (F >= 2) was
      measured as the area under the curve (AUROC = 0.865), and it demonstrated that
      the method had a good diagnostic performance. APRI was not so accurate in
      assessing graft fibrosis when compared to METAVIR (AUROC = 0.592). A liver
      stiffness cutoff value of 5.6 kPa at TE was identified as the best predictor for
      a significant graft fibrosis (METAVIR F >= 2) on liver biopsy, with a 75%
      sensitivity, a 95.8% specificity, a 90% positive predictive value, and an 88.5%
      negative predictive value. These data suggest that TE may represent a non
      invasive, reliable tool for the assessment of graft fibrosis in the follow-up of
      LT children, alerting the clinicians to the indication for a liver biopsy, with
      the aim of reducing the number of protocol liver biopsies.

PMID- 29369490
TI  - Neural crest emigration: From start to stop.
AB  - Within the dynamic context of a developing embryo, the multicellular patterns
      formed are extraordinarily precise. Through cell-cell communication, neighboring
      progenitors coordinate their activities, sequentially generating distinct
      tissues. The development of the dorsal neural tube remarkably illustrates this
      principle. It first generates neural crest (NC) cells, precursors of most of the
      peripheral nervous system, and then becomes the roof plate (RP) of the central
      nervous system. While the molecular network regulating emigration of NC
      progenitors has been extensively studied, the mechanisms by which dorsal neural
      tube precursors transit from an initial NC fate to a definitive RP identity
      remain widely open to investigation. Critical differences exist between
      premigratory NC and RP cells. Whereas the former extensively proliferate and
      undergo an epithelial-to-mesenchymal transition that generates cellular
      migrations, the latter progressively exit the cell cycle and regain epithelial
      traits including apico-basal polarity and regeneration of a laminin-containing
      basement membrane. To understand this transition, the nature of the cross-talk
      between these two sequentially forming progenitor subsets should be unraveled,
      including the identity and mode of action of signals that, on the one hand,
      induce the arrest of NC emigration, and, on the other hand, promote formation of
      a definitive RP.

PMID- 29369491
TI  - Glucose-6-phosphate dehydrogenase deficiency in internationally adopted children.
AB  - There are conflicting guidelines about screening of internationally adopted
      children for glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common
      genetic disorder. In a multi-ethnic population of 2,169 internationally adopted
      children, we found that the prevalence of G6PD deficiency was 1.6% overall and
      2.2% in males. Prevalence differed by country or region of origin, ranging from 0
      to 13% overall and 0 to 22% in males. The prevalence in females was 1%. A
      diagnosis of G6PD deficiency informs the treatment of malaria and enables
      education and counseling to prevent morbidity and mortality from G6PD deficiency.
      Screening for G6PD deficiency should be strongly considered for internationally
      adopted children.

PMID- 29369492
TI  - Biological Activity of an Injectable Biphasic Calcium Phosphate/PMMA Bone Cement
      for Induced Osteogensis in Rabbit Model.
AB  - Polymethylmethacrylate (PMMA) bone cement is widely used in repair of vertebral
      fracture because of its good biomechanical properties and fast curing. However,
      the bioinertness of PMMA cement may cause interfacial loosening, fatigue,
      fracture, and ultimate failure. In this study, biphasic calcium phosphate (BCP)
      is introduced into PMMA cement to prepare an injectable composite bone cement
      (BCPx /PMMA) and the content of BCP is optimized to achieve appropriate rate of
      absorption that matches the bone regeneration. The compressive strength of BCPx
      /PMMA bone cement is found to comply with the International Standardization
      Organization standard 5833, and can promote biomineralization as well as
      adhesion, proliferation, and osteogenic differentiation of Sprague-Dawley rat
      bone marrow mesenchymal stem cells in vitro. Furthermore, in vivo test performed
      on a rabbit radius defect model demonstrates that the presence of BCP can
      significantly improve the osteogenic efficacy of PMMA cement. Therefore, it is
      anticipated that BCPx /PMMA bone cement, as a promising injectable biomaterial,
      is of great potential in bone tissue regeneration.

PMID- 29369493
TI  - Injecting without pressing a button: An exploratory study of a shield-triggered
      injection mechanism.
AB  - AIMS: To evaluate the injection success and user perception of a shield-triggered
      pen-injector mechanism. METHODS: The trial (ClinicalTrials.gov NCT02627287) was
      an exploratory, two-centre, one-visit, open-label, randomized controlled trial
      conducted in Germany in 150 injection-experienced individuals with type 1 or type
      2 diabetes. Participants self-administered subcutaneous injections of a placebo
      solution using a prototype shield-triggered pen-injector, DV3316 (Novo Nordisk,
      Bagsvaerd, Denmark), and FlexPen (Novo Nordisk, Bagsvaerd, Denmark). Injection
      success was evaluated on a yes/no basis by the investigator. Participant
      confidence, leakage of fluid and pain were evaluated after each injection. Pain
      and device experience were assessed after completion of all injections with each
      pen-injector. Overall preference was assessed after completion of all injections
      with both pen-injectors. RESULTS: Injection success was high with both pen
      injectors (97.0%, DV3316 vs 99.7%, FlexPen). Participant confidence in dose
      delivery was similar for the two devices (88% of injections with DV3316 vs 81%
      with FlexPen were scored as "extremely confident"). The median injection pain
      score on a visual analogue scale (0-100) was 3 with DV3316 vs 4 with FlexPen
      after each injection, and 4 with DV3316 vs 5 with FlexPen after all injections
      with each device. After all injections were completed, 55% of participants
      reported an overall preference for DV3316 vs 21% for FlexPen. CONCLUSION: This
      study demonstrates that injection-experienced individuals can achieve a high
      injection success rate with a shield-triggered pen-injector, with similar patient
      confidence and injection pain compared with FlexPen.

PMID- 29369494
TI  - Comparisons of diabetic retinopathy events associated with glucose-lowering drugs
      in patients with type 2 diabetes mellitus: A network meta-analysis.
AB  - AIM: To assess the comparative effects of glucose-lowering drugs (GLDs) on the
      risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus
      (T2DM). METHODS: We systematically searched Cochrane Central Register of
      Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to
      identify randomized controlled trials (RCTs) that reported DR events among T2DM
      patients receiving any GLD. Random-effects pairwise and network meta-analyses
      were performed to calculate odds ratios (ORs) with 95% confidence intervals
      (CIs). RESULTS: A total of 37 independent RCTs with 1806 DR events among 100 928
      patients with T2DM were included. The mean duration of diabetes was 8.7 years and
      mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta-analysis found that DPP
      4i (OR, 1.20; 95% CI, 0.87-1.65), GLP-1RA (OR, 1.19; 95% CI, 0.94-1.52) and SGLT2
      inhibitors (OR, 0.79; 95% CI, 0.49-1.28) were not associated with a higher risk
      of DR than placebo; however, a significantly increased risk of DR was associated
      with DPP-4i in the pairwise meta-analysis (OR, 1.27; 95% CI, 1.05-1.53).
      Sulfonylureas, on the other hand, were associated with a significantly increased
      risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01-2.76). CONCLUSIONS:
      Current evidence indicates that the association between DPP-4i, GLP-1RA or SGLT2
      inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence
      suggests that sulfonylureas may be associated with increased risk of DR. However,
      given that DR events were not systematically assessed, these effects should be
      explored further in large-scale, well-designed studies.

PMID- 29369495
TI  - Pentachloropseudilin Inhibits Transforming Growth Factor-beta (TGF-beta) Activity
      by Accelerating Cell-Surface Type II TGF-beta Receptor Turnover in Target Cells.
AB  - Pentachloropseudilin (PClP) is a chlorinated phenylpyrrole compound that was
      first isolated from Actinoplanes (ATCC33002), and its structure has been
      confirmed by chemical synthesis. PClP shows broad antimicrobial activity against
      Gram-negative and Gram-positive bacteria, protozoa, fungi, and yeast. In
      mammalian cells, PClP is known to act as a reversible and allosteric inhibitor of
      myosin 1c (Myo1c). Herein, we report that PCIP is a potent inhibitor of
      transforming growth factor-beta (TGF-beta)-stimulated signaling. PCIP inhibits
      TGF-beta-stimulated Smad2/3 phosphorylation and plasminogen activator inhibitor-1
      (PAI-1) promoter activation with an IC50 of 0.1 MUm in target cells (A549, HepG2,
      and Mv1Lu cells). In addition, PCIP attenuates TGF-beta-stimulated expression of
      vimentin, N-cadherin, and fibronectin and, thus, blocks TGF-beta-induced
      epithelial to mesenchymal transition (EMT) in these cells. Furthermore, cell
      surface labeling and immunoblot analysis indicates that PCIP suppresses TGF-beta
      stimulated cellular responses by attenuating cell-surface expression of the type
      II TGF-beta receptor through accelerating caveolae-mediated internalization
      followed by primarily lysosome-dependent degradation of the receptor, as
      demonstrated by sucrose density gradient analysis and immune fluorescence
      staining.

PMID- 29369496
TI  - Photo-Reconfigurable Azopolymer Etch Mask: Photofluidization-Driven
      Reconfiguration and Edge Rectangularization.
AB  - Directional photofluidization of azobenzene materials has provided unprecedented
      opportunities for the structural reconfiguration of circular holes, line gaps,
      ellipsoidal holes, and nanofunnel-shaped micro/nanoarchitectures. However, all
      the reconfigured structures have a parabolic or round wall due to the tendency of
      the photofluidized azobenezene materials to minimize the surface area, which
      limits their use as a reconfigurable etch-mask for the lithography process. In
      this work, a simple method is presented that can change the round walls of
      azopolymer architectures into rectangular walls, which is named
      rectangularization. By irradiating far-field light on reconfigured azopolymer in
      a conformal contact with a flat polydimethylsiloxane (PDMS) film, the round wall
      transforms to a rectangular one because the azopolymer adheres along the PDMS
      surface while being photofluidized. As a result, the rectangularization process
      creates a variety of structural features and sizes ranging from a few micrometers
      to 150 nm having a rectangular wall. By exploiting the rectangularization
      process, the concept of a photo-reconfigurable etch mask is achieved, which
      transfers the mask patterns to a silicon pattern with a high structural fidelity
      and imparts a considerable flexibility to the lithography process.

PMID- 29369497
TI  - Pharmacogenetics of Risperidone-Induced Insulin Resistance in Children and
      Adolescents with Autism Spectrum Disorder.
AB  - The purpose of this study was to explore the association of genetic polymorphism
      of genes related to pharmacokinetics or pharmacodynamics with insulin resistance
      in children and adolescents with autism spectrum disorder (ASD) and treated with
      risperidone. All 89 subjects underwent measurement of fasting blood glucose and
      insulin levels, body-weight and height. Genotyping was performed by TaqMan real
      time polymerase chain reaction (PCR) (pharmacokinetics genes: cytochrome P450 2D6
      (CYP2D6) *4 (rs3892097), *5 (gene deletion), *10 (rs1065852) and *41
      (rs28371725), ATP-binding cassette transporter B1 (ABCB1) 2677 G>T/A (rs2032582)
      and 3435C>T (rs1045642) and pharmacodynamics genes: dopamine receptor D2 (DRD2)
      Tag-SNP (C>T) (rs4436578), DRD2 Tag1A (C>T) (rs1800497), leptin gene (LEP) 
      2548G>A (rs7799039), ghrelin gene (GHRL) -604G>A (rs27647) and brain-derived
      neurotrophic factor (BDNF) 196G>A (rs6265)). Drug levels were analysed by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The results revealed that 5
      (5.62%) patients presented with hyperglycaemia. Insulin resistance was detected
      in 15 (16.85%) patients. Insulin resistance was associated with LEP 2548 G>A and
      BDNF 196 G>A polymorphism (p = 0.051 and p = 0.03). There was no association of
      pharmacokinetic gene polymorphisms (CYP2D6 and ABCB1) and risperidone levels with
      insulin resistance. Multiple regression analysis indicated that BDNF 196 G>A
      polymorphism was significantly associated with insulin resistance (p = 0.025).
      This finding suggested that BDNF 196 G>A polymorphism may be a genetic marker for
      predicting insulin resistance before initiating treatment in patients treated
      with risperidone. Because of the small sample size, further studies are needed to
      confirm these results.

PMID- 29369498
TI  - Palladium-Decorated Silicon Nanomesh Fabricated by Nanosphere Lithography for
      High Performance, Room Temperature Hydrogen Sensing.
AB  - A hydrogen (H2 ) gas sensor based on a silicon (Si) nanomesh structure decorated
      with palladium (Pd) nanoparticles is fabricated via polystyrene nanosphere
      lithography and top-down fabrication processes. The gas sensor shows dramatically
      improved H2 gas sensitivity compared with an Si thin film sensor without
      nanopatterns. Furthermore, a buffered oxide etchant treatment of the Si nanomesh
      structure results in an additional performance improvement. The final sensor
      device shows fast H2 response and high selectivity to H2 gas among other gases.
      The sensing performance is stable and shows repeatable responses in both dry and
      high humidity ambient environments. The sensor also shows high stability without
      noticeable performance degradation after one month. This approach allows the
      facile fabrication of high performance H2 sensors via a cost-effective,
      complementary metal-oxide-semiconductor (CMOS) compatible, and scalable
      nanopatterning method.

PMID- 29369499
TI  - Inducibly decreased MITF levels do not affect proliferation and phenotype
      switching but reduce differentiation of melanoma cells.
AB  - Melanoma arises from neural crest-derived melanocytes which reside mostly in the
      skin in an adult organism. Epithelial-mesenchymal transition (EMT) is a
      tumorigenic programme through which cells acquire mesenchymal, more pro-oncogenic
      phenotype. The reversible phenotype switching is an event still not completely
      understood in melanoma. The EMT features and increased invasiveness are
      associated with lower levels of the pivotal lineage identity maintaining and
      melanoma-specific transcription factor MITF (microphthalmia-associated
      transcription factor), whereas increased proliferation is linked to higher MITF
      levels. However, the precise role of MITF in phenotype switching is still loosely
      characterized. To exclude the changes occurring upstream of MITF during MITF
      regulation in vivo, we employed a model whereby MITF expression was inducibly
      regulated by shRNA in melanoma cell lines. We found that the decrease in MITF
      caused only moderate attenuation of proliferation of the whole cell line
      population. Proliferation was decreased in five of 15 isolated clones, in three
      of them profoundly. Reduction in MITF levels alone did not generally produce EMT
      like characteristics. The stem cell marker levels also did not change
      appreciably, only a sharp increase in SOX2 accompanied MITF down-regulation.
      Oppositely, the downstream differentiation markers and the MITF transcriptional
      targets melastatin and tyrosinase were profoundly decreased, as well as the
      downstream target livin. Surprisingly, after the MITF decline, invasiveness was
      not appreciably affected, independently of proliferation. The results suggest
      that low levels of MITF may still maintain relatively high proliferation and
      might reflect, rather than cause, the EMT-like changes occurring in melanoma.

PMID- 29369500
TI  - Insights from Proteomic Studies into Plant Somatic Embryogenesis.
AB  - Somatic embryogenesis is a biotechnological approach mainly used for the clonal
      propagation of different plants worldwide. In somatic embryogenesis, embryos
      arise from somatic cells under appropriate culture conditions. This plasticity in
      plants is a demonstration of true cellular totipotency and is the best approach
      among the genetic transformation protocols used for plant regeneration. Despite
      the importance of somatic embryogenesis, knowledge regarding the control of the
      somatic embryogenesis process is limited. Therefore, the elucidation of both the
      biochemical and molecular processes is important for understanding the mechanisms
      by which a single somatic cell becomes a whole plant. Modern proteomic techniques
      rely on an alternative method for the identification and quantification of
      proteins with different abundances in embryogenic cell cultures or somatic
      embryos and enable the identification of specific proteins related to somatic
      embryogenesis development. This review focuses on somatic embryogenesis studies
      that use gel-free shotgun proteomic analyses to categorize proteins that could
      enhance our understanding of particular aspects of the somatic embryogenesis
      process and identify possible targets for future studies.

PMID- 29369501
TI  - Targeted therapy for infants with diencephalic syndrome: A case report and review
      of management strategies.
AB  - Young children with emaciation caused by a hypothalamic glioma are considered to
      have diencephalic syndrome (DS), which is often poorly controlled with
      conventional treatment. We describe an infant with DS whose tumor progressed
      following chemotherapy. Biopsy was performed for molecular testing and
      demonstrated a BRAF fusion. Treatment with the MEK inhibitor trametinib for 18
      months resulted in reduction of tumor size, normalization of his weight curve,
      and marked neurodevelopmental improvement. Our results build on earlier reports
      of using targeted agents for low-grade glioma, and we review the evolving
      management strategy for such patients in the era of precision medicine.

PMID- 29369503
TI  - Magnetic resonance elastography of liver and spleen: Methods and applications.
AB  - The viscoelastic properties of the liver and spleen can be assessed with magnetic
      resonance elastography (MRE). Several actuators, MRI acquisition sequences and
      reconstruction algorithms have been proposed for this purpose. Reproducible
      results are obtained, especially when the examination is performed in standard
      conditions with the patient fasting. Accurate staging of liver fibrosis can be
      obtained by measuring liver stiffness or elasticity with MRE. Moreover, emerging
      evidence shows that assessing the tissue viscous parameters with MRE is useful
      for characterizing liver inflammation, non-alcoholic steatohepatitis, hepatic
      congestion, portal hypertension, and hepatic tumors. Further advances such as
      multifrequency acquisitions and compression-sensitive MRE may provide novel
      quantitative markers of hepatic and splenic mechanical properties that may
      improve the diagnosis of hepatic and splenic diseases.

PMID- 29369502
TI  - SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion
      and induce apoptosis.
AB  - Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It
      contains at least four distinct molecular subgroups. The aim of this study is to
      explore novel diagnostic and potential therapeutic markers within each subgroup
      of MB, in particular within Group 4, the largest subgroup, to facilitate
      diagnosis together with gene therapy. One hundred and six MB samples were
      examined. Tumor subtype was evaluated with the NanoString assay. Several novel
      tumor related genes were shown to have high subgroup sensitivity and specificity,
      including PDGFRA, FGFR1, and ALK in the WNT group, CCND1 in the SHH group, and
      alpha-synuclein (SNCA) in Group 4. Knockdown and overexpression assays of SNCA
      revealed the ability of this gene to inhibit tumor invasion and induce apoptosis.
      Methylation-specific PCR and pyrosequencing analysis showed that epigenetic
      mechanisms, rather than DNA hypermethylation, might play the key role in the
      regulation of SNCA expression in MB tumors. In conclusion, we identify SNCA as a
      novel diagnostic biomarker for Group 4 MB. Some other subgroup signature genes
      have also been found as candidate therapeutic targets for this tumor.

PMID- 29369505
TI  - Age-related change and sex difference over 60s in disc-fovea angle in Japanese
      population: the Nagahama Study.
AB  - PURPOSE: To analyse the disc-fovea angle (DFA) by age group and to compare sex
      differences in each age group in a large cohort population. METHODS: This
      community-based cross-sectional cohort study included 9682 eyes of 9682
      volunteers (aged 30-75 years). We measured the DFA, which is the angle between a
      horizontal line and a line connecting the fovea with the centroid of an optic
      disc on fundus photographs of the right eye. We manually marked the fovea and
      surrounded the optic disc. The centroid of an optic disc and the DFA was
      automatically calculated using originally developed software. We compared the DFA
      between age groups in 10-year increments and investigated sex differences of DFA
      in each age group. RESULTS: Overall mean DFA was 6.32 +/- 3.53 degrees . The DFA
      of older subjects was significantly larger than that of younger subjects (p <
      0.001). The DFA of women was larger than that of men in their 60s and 70s (p <
      0.001 for both), but not in subjects in their 30s, 40s and 50s. CONCLUSION:
      Larger DFA in women than in men in their 60s and 70s suggests the possibility
      that age-related excyclo-shift occurs more easily in postmenopausal women
      compared to men of the same age.

PMID- 29369504
TI  - Analyzing multiple pesticides in tobacco leaf using gas chromatography with
      quadrupole time-of-flight mass spectrometry.
AB  - A method combining gas chromatography with quadrupole time-of-flight mass
      spectrometry has been developed for the simultaneous analysis of multiple
      pesticide residues in tobacco leaf. The retention index and high accurate masses
      of ions from the first-stage and the second-stage mass spectra of each pesticide
      were collected for qualitation and quantification. A total of 115 pesticides were
      evaluated. The extract from organic tobacco leaf was used as a model matrix. The
      limit of detection was <10 ng/mL, and the limit of quantification was in the
      range of 1-20 ng/mL for 95% of the tested pesticides. The correlation
      coefficients were >0.9900 for all tested pesticides. At three concentrations (10,
      50, and 100 ng/mL), most compounds presented satisfactory recoveries ranging from
      70 to 120% and good precision <20%. Finally, three tobacco leaf samples collected
      from a local market were analyzed. A total of three pesticides were found,
      including dimethachlon, triadimenol, and flumetralin. Each pesticide was
      confirmed by the presence of three ions at the expected retention index and mass.
      In conclusion, gas chromatography with quadrupole time-of-flight mass
      spectrometry appears to be one of the most efficient tools for the analysis of
      pesticide residues in tobacco leaf.

PMID- 29369506
TI  - Diabetic retinopathy in type 1 diabetes patients in Western Norway.
AB  - PURPOSE: To describe the prevalence of diabetic retinopathy (DR), associated risk
      factors and health-related quality of life (HRQoL) in a population-based cohort
      of patients with type 1 diabetes mellitus (DM1). METHODS: All patients underwent
      a general and ophthalmic examination including seven-field stereo fundus
      photography for grading of DR and diabetic macular oedema (DMO). Kaplan-Meier
      survival analyses were performed to evaluate disease progression in relation to
      diabetes duration, age and year of diabetes onset. HRQoL and its association with
      DR were assessed by the Medical Outcomes Study Short Form 36 (SF-36)
      questionnaire. RESULTS: A total of 237 DM1 patients were included. Mean age at
      inclusion was 34 years (range, 4-75 years), and mean diabetes duration was 19
      years (range, 5 months-63 years). A total of 145 patients (61%) had DR. Sixty-two
      patients (26%) had mild, 39 (16%) moderate and 13 (5%) severe nonproliferative
      DR, while 31 (13%) had proliferative DR. The prevalence of DMO was 8%. The most
      important risk factors predicting severity of DR were diabetes duration (p <
      0.0001) and HbA1c level (p < 0.0001). Neuropathy (p = 0.006), nephropathy (p =
      0.004) and male gender (p = 0.02) were also significant predictors of DR.
      Compared to normative SF-36 data, there was a linear trend of decreasing HRQoL
      with increasing severity of DR that was statistically significant for the four
      physical dimension scores. CONCLUSION: The prevalence of DR in DM1 was largely
      within the range of previous reports. Diabetes duration, HbA1c level, neuropathy,
      nephropathy and male gender were all significant predictors of DR severity. The
      patients with more severe DR had lower HRQoL.

PMID- 29369507
TI  - Why near-peer teaching should be in the Teaching Excellence Framework assessment.

PMID- 29369508
TI  - Age-related changes in with-the-rule and oblique corneal astigmatism.
AB  - PURPOSE: To describe the age-related changes in with-the-rule (WTR) and oblique
      keratometric astigmatism (KA), posterior corneal astigmatism (PCA) and total
      corneal astigmatism (TCA). METHODS: We used a Pentacam HR (high-resolution)
      rotating Scheimpflug camera to determine the KA, PCA and TCA in the right eyes of
      710 patients, aged from 20 to 88 years. The age-related changes along the
      vertical, horizontal and oblique meridians were analyzed with Naeser's polar
      value method in a cross-sectional study. RESULTS: In the whole group, all
      meridional astigmatic powers and polar values were stable in the age groups from
      20 to 49 years, followed by a 1.0 dioptre (D) against-the-rule (ATR) change in KA
      and TCA, and a 0.12 D reduction in against-the-rule PCA. A nasal rotation of the
      steep meridian in KA and TCA was noted in the 70-88 years old. The PCA averaged
      approximately 0.25 D ATR in all age groups. Females displayed the same early
      astigmatic stability as in the whole group, while male eyes demonstrated a linear
      decay from 1.5 D WTR at 20 years to 0.5 D ATR astigmatism for the oldest
      patients. CONCLUSION: Corneal astigmatism is stable until the age of 50 years;
      thereafter both keratometric and total corneal astigmatism show a 0.25 D ATR
      change per 10 years. The average 0.25 D ATR PCA compensates the predominant
      keratometric WTR astigmatism in the younger patients and increases the TCA in the
      elderly with keratometric ATR astigmatism. The gender-based differences in age
      related astigmatism require further studies.

PMID- 29369509
TI  - Insights into the Effect of Structural Heterogeneity in Carbonized Electrospun
      Fibrous Mats for Flow Battery Electrodes by X-Ray Tomography.
AB  - Electrospun custom made flow battery electrodes are imaged in 3D using X-ray
      computed tomography. A variety of computational methods and simulations are
      applied to the images to determine properties including the porosity, fiber size,
      and pore size distributions as well as the material permeability and flow
      distributions. The simulations are performed on materials before and after
      carbonization to determine the effect it has in the internal microstructure and
      material properties. It is found that the deposited fiber size is constantly
      changing throughout the electrospinning process. The results also show that the
      surfaces of the fibrous material are the most severely altered during
      carbonization and that the rest of the material remained intact. Pressure driven
      flow is modeled using the lattice Boltzmann method and excellent agreement with
      experimental results is found. The simulations coupled with the material analysis
      also demonstrate the highly heterogeneous nature of the flow. Most of the flow is
      concentrated to regions with high porosity while regions with low porosity shield
      other pores and starve them of flow. The importance of imaging these materials in
      3D is highlighted throughout.

PMID- 29369510
TI  - Development and evaluation of brochures for fall prevention education created to
      empower nursing home residents and family members.
AB  - AIMS AND OBJECTIVES: In this study, we describe the development of evidence- and
      theory-based fall prevention educational material and its evaluation from the
      users' perspectives. BACKGROUND: To reduce risk factors for falling in nursing
      homes, nursing staff must enact multifactorial fall prevention intervention
      programmes. A core component of these programmes is to educate residents and
      their family members, both verbally and in a written form. However, users can
      only benefit from educational material if it is based on current scientific
      evidence, easy to understand and process and customised. DESIGN: We followed a
      structured procedure during the development process, while considering various
      aspect of quality. To assess the understandability and usefulness of the
      resulting educational materials, we conducted a qualitative content analysis
      study. METHODS: The educational materials development process incorporated
      several iterative steps including a systematic literature search and the
      application of frameworks for designing and writing the materials. To evaluate
      the material, we performed six focus group discussions separately with residents,
      family members and nursing staff from two nursing homes (total of 32
      participants). RESULTS: Residents' brochures included clear information on
      avoiding external risks as well as coping strategies after a fall event. Family
      members' brochures were more comprehensive, including both concrete tips and
      outlining the advantages and disadvantages of interventions. Residents and family
      members had no difficulties understanding the material and tried to apply the
      content to their individual situations. Nursing staff commented on some
      ambiguities and incongruities relating to current nursing care practice.
      CONCLUSIONS: By involving users in the development of evidence-based educational
      materials, nursing staff can achieve a high acceptance rate for the materials and
      motivate users to address the topic. IMPLICATIONS FOR PRACTICE: The involvement
      of users is essential for developing educational material that meets users'
      needs. Educational material should be used as part of an overall strategy to
      educate residents and family members in nursing homes.

PMID- 29369511
TI  - Preparation of iron-based MIL-101 functionalized polydopamine@Fe3 O4 magnetic
      composites for extracting sulfonylurea herbicides from environmental water and
      vegetable samples.
AB  - Here, we describe a simple one-pot solvothermal method for synthesizing MIL
      101(Fe)@polydopamine@Fe3 O4 composites from polydopamine-modified Fe3 O4
      particles. The composite was used as a magnetic adsorbent to rapidly extract
      sulfonylurea herbicides. The herbicides were then analyzed by high-performance
      liquid chromatography. The best possible extraction efficiencies were achieved by
      optimizing the most important extraction parameters, including desorption
      conditions, extraction time, adsorbent dose, salt concentration, and the pH of
      the solution. Good linearity was found (correlation coefficients >0.9991) over
      the herbicide concentration range 1-150 MUg/L using the optimal conditions. The
      limits of detection (the concentrations giving signal/noise ratios of 3) were
      low, at 0.12-0.34 MUg/L, and repeatability was good (the relative standard
      deviations were <4.8%, n = 6). The method was used successfully to determine four
      sulfonylurea herbicides in environmental water and vegetable samples, giving
      satisfactory recoveries of 87.1-108.9%. The extraction efficiency achieved using
      MIL-101(Fe)@polydopamine@Fe3 O4 was compared with the extraction efficiencies
      achieved using other magnetic composites (polydopamine@Fe3 O4 , Hong Kong
      University of Science and Technology (HKUST)-1@polydopamine@Fe3 O4 , and MIL
      100(Fe)@polydopamine@Fe3 O4 ). The results showed that the magnetic MIL
      101(Fe)@polydopamine@Fe3 O4 composites have great potential for the extraction of
      trace sulfonylurea herbicides from various sample types.

PMID- 29369512
TI  - A new fluorescent chemosensor for cadmium(II) based on a pyrene-appended
      piperidone derivative and its beta-cyclodextrin complex.
AB  - We report, in this article, a piperidin-4-one derivative carrying pyrenyl
      fluorescent reporter groups which acts as a Cd2+ ion sensor. The compound is
      synthesized and characterized using IR and NMR spectral techniques. The compound
      forms an inclusion complex with beta-cyclodextrin. It selectively binds to Cd2+
      ions in water and aqueous beta-cyclodextrin media. The stoichiometry of the host
      guest complex of the compound with beta-cyclodextrin is 1:2. The ligand-metal ion
      binding stoichiometry is 1:1 both in water and in beta-cyclodextrin. The linear
      concentration range of detection of the metal ion is reported. Cyclodextrin
      complex formation does not affect the metal ion selectivity of the compound.

PMID- 29369513
TI  - Integrating Doulas Into First-Trimester Abortion Care: Physician, Clinic Staff,
      and Doula Experiences.
AB  - INTRODUCTION: Balancing the need to provide individual support for patients and
      the need for an efficient clinic can be challenging in the abortion setting. This
      study explores physician, staff, and specially trained abortion doula
      perspectives on doula support, one approach to patient support. METHODS: We
      conducted separate focus groups with physicians, staff members, and doulas from a
      high-volume, first-trimester aspiration abortion clinic with a newly established
      volunteer abortion doula program. Focus groups explored 1) abortion doula
      training, 2) program implementation, 3) program benefits, and 4) opportunities
      for improvement. Interviews were transcribed and computer-assisted content
      analysis was performed; salient findings are presented. RESULTS: Five physicians,
      5 staff members, and 4 abortion doulas participated in separate focus group
      discussions. Doulas drew on both their prior personal skills and experiences in
      addition to their abortion doula training to provide women with support at the
      time of abortion. Having doulas in the clinic to assist with women's emotional
      needs allowed physicians and staff to focus on technical aspects of the
      procedure. In turn, both physicians and staff believed that introducing doulas
      resulted in more patient-centered care. Although staff did not experience
      challenges to integrating doulas, physicians and doulas experienced initial
      challenges in incorporating doula support into the clinical flow. Staff and
      doulas reported exchanging skills and techniques that they subsequently used in
      their interactions with patients. DISCUSSION: Physicians, clinic staff, and
      doulas perceive abortion doula support as an approach to provide more patient
      centered care in a high-volume aspiration abortion clinic.

PMID- 29369514
TI  - A workshop to promote interprofessional care.
AB  - BACKGROUND: Paediatric incontinence has traditionally been managed through a
      discipline-specific approach by doctors, nurses, physiotherapists and
      psychologists. We evaluated a workshop aiming to increase health professionals'
      knowledge, confidence and willingness to involve other health professionals when
      managing paediatric incontinence. METHODS: Our 1-day workshop focused on
      paediatric bedwetting, daytime incontinence, faecal incontinence and neurogenic
      bladder. Attendees completed surveys before and after the workshop, and 6 months
      later. Differences between health professionals and changes in attitudes,
      knowledge, confidence and experience before and after the workshop were analysed
      using descriptive analysis. Qualitative data analysis was undertaken using
      content analysis. RESULTS: The workshop was attended by 77 clinicians (41
      doctors, 19 allied health professionals and 17 nurses). Over two-thirds of
      respondents acknowledged having average or above average knowledge of and/or
      confidence in managing bedwetting, daytime urinary incontinence (DUI) and faecal
      incontinence, with lower baseline knowledge and confidence for neurogenic
      bladder. Participants who completed the initial and final surveys reported
      increased knowledge, improved ability to manage patients, better appreciation of
      the contribution of other disciplines and willingness to refer patients to other
      disciplines. Of those who saw patients with incontinence, most reported that the
      workshop had improved their management: 33/35 for bedwetting; 31/35 for DUI;
      21/29 for faecal incontinence; and 16/19 for neurogenic bladder. Paediatric
      incontinence has traditionally been managed through a discipline-specific
      approach by doctors, nurses, physiotherapists and psychologists DISCUSSION: This
      study demonstrates that an interprofessional workshop conducted by clinicians
      from different health professional backgrounds increases clinicians' awareness of
      the roles of other disciplines and promotes the development of an
      interdisciplinary approach or multiprofessional collaboration, enabling a more
      effective, patient-centred, collaborative care model.

PMID- 29369515
TI  - Reirradiation in patients with diffuse intrinsic pontine gliomas: The Canadian
      experience.
AB  - OBJECTIVE: Clinical trials have failed to demonstrate a survival benefit of
      adjuvant chemotherapy in diffuse intrinsic pontine gliomas (DIPG). Radiation
      therapy (RT) is the only effective treatment thus far and reirradiation (rRT) has
      become an option at the time of progression. The aim of this study was to review
      the Canadian experience of DIPG rRT with a focus on the safety and possible
      efficacy of this approach. METHOD: We retrospectively reviewed the demographic,
      clinical, and RT data of patients with DIPG treated in Canada with rRT. RESULTS:
      Since January 2011, we identified 16 patients with progressive DIPG who received
      rRT. Median time from diagnosis to progression was 10.5 months (range, 4-37
      months). rRT was given focally in 14 patients at a dose ranging from 21.6 to 36
      Gy. rRT was well tolerated by all children but one. All but three patients showed
      neurological improvement. With a median follow-up from original diagnosis of 19.2
      months, all patients died, with a median time from rRT to death of 6.48 months
      (range, 3.83-13.26 months). When compared to a historic cohort of 46 consecutive
      patients, the median time from progression to death was 92 days in the non
      reirradiated patients versus 218 days in the reirradiated ones (P = 0.0001).
      CONCLUSION: In this limited experience, rRT was safe and feasible in patients
      with progressive DIPG, providing neurological improvement and a prolonged life
      span in most patients. Prospective Canadian rRT protocols are ongoing to further
      assess the benefit of this approach, including quality of life assessment.

PMID- 29369516
TI  - Prevalence of optical coherence tomography detected vitreomacular interface
      disorders: The Maastricht Study.
AB  - PURPOSE: To calculate the prevalence of all vitreomacular interface (VMI)
      disorders and stratify according to age, sex and (pre)diabetes status. METHODS:
      The presence of VMI disorders was assessed in 2660 participants aged between 40
      and 75 years from The Maastricht Study who had a gradable macular spectral-domain
      optical coherence tomography (SD-OCT) volume scan in at least one eye [mean 59.7
      +/- 8.2 years, 50.2% men, 1531 normal glucose metabolism (NGM), 401 prediabetes,
      728 type 2 diabetes (DM2, oversampled)]. A stratified and multivariable logistic
      regression analysis was used. RESULTS: The prevalence of the different VMI
      disorders for individuals with NGM, prediabetes and DM2 was, respectively, 5.7%,
      6% and 6.7% for epiretinal membranes; 6%, 9.6% and 6.8% for vitreomacular
      traction; 1.1%, 0.7% and 0.3% for lamellar macular holes; 0.1%, 0% and 0% for
      pseudoholes; 1.1%, 1.9% and 5.5% for macular cysts. None of the participants was
      diagnosed with a macular hole. The prevalence of epiretinal membranes,
      vitreomacular traction and macular cysts was higher with age (p < 0.001).
      Vitreomacular traction and lamellar macular holes were more frequent in women (p
      < 0.01). DM2 is positively associated [OR = 3.9 (95% CI 2.11-7.22, p < 0.001)]
      with macular cysts and negatively associated with lamellar macular holes [OR =
      0.2 (95% CI 0.04-0.9, p = 0.036)] after adjustment for age and sex. The
      calculated prevalence of VMI disorders was 15.9%. CONCLUSIONS: The calculated
      prevalence of VMI disorders in individuals aged between 40 and 75 years is 15.9%.
      The prevalence depends on age, sex and glucose metabolism status for several
      types of VMI disorders.

PMID- 29369517
TI  - Causes and timing of end-stage renal disease after living kidney donation.
AB  - End-stage renal disease (ESRD) is a risk after kidney donation. We sought, in a
      large cohort of kidney donors, to determine the causes of donor ESRD, the
      interval from donation to ESRD, the role of the donor/recipient relationship, and
      the trajectory of the estimated GFR (eGFR) from donation to ESRD. From 1/1/1963
      thru 12/31/2015, 4030 individuals underwent living donor nephrectomy at our
      center, as well as ascertainment of ESRD status. Of these, 39 developed ESRD
      (mean age +/- standard deviation [SD] at ESRD, 62.4 +/- 14.1 years; mean interval
      between donation and ESRD, 27.1 +/- 9.8 years). Donors developing ESRD were more
      likely to be male, as well as smokers, and younger at donation, and to have
      donated to a first-degree relative. Of donors with a known cause of ESRD (n =
      25), 48% was due to diabetes and/or hypertension; only 2 from a disease that
      would have affected 1 kidney (cancer). Of those 25 with an ascertainable ESRD
      cause, 4 shared a similar etiology of ESRD with their recipient. Almost
      universally, thechange of eGFR over time was stable, until new-onset disease
      (kidney or systemic). Knowledge of factors contributing to ESRD after living
      kidney donation can improve donor selection and counseling, as well as long-term
      postdonation care.

PMID- 29369518
TI  - Asymptomatic neurotrophic keratitis in carotid-cavernous fistulae.

PMID- 29369519
TI  - Molecular Farming in Barley: Development of a Novel Production Platform to
      Produce Human Antimicrobial Peptide LL-37.
AB  - The peptide LL-37, a component of the human innate immune system, represents a
      promising drug candidate. In particular, the development of low-cost production
      platform technology is a critical bottleneck in its use in medicine. In the
      present study, a viable approach for the LL-37 production in transgenic barley is
      developed. First, comparative analyses of the effects of different fused peptide
      epitope tags applicable for accumulation and purification on LL-37 production
      yield are performed using transient expression in tobacco leaves. Following the
      selection of the most yielding fusion peptide strategies, eight different
      constructs for the expression of codon optimized chimeric LL-37 genes in
      transgenic barley plants are created. The expression of individual constructs is
      driven either by an endosperm-specific promoter of the barley B1 hordein gene or
      by the maize ubiquitin promoter. The transgenes are stably integrated into the
      barley genome and inherited in the subsequent generation. All transgenic lines
      show normal phenotypes and are fertile. LL-37 accumulated in the barley seeds up
      to 0.55 mg per 1 kg of grain. The fused epitope tags are cleaved off by the use
      of enterokinase. Furthermore, in planta produced LL-37 including the fused
      versions is biologically active.

PMID- 29369520
TI  - The review of refractive studies of nonadults in Poland.

PMID- 29369521
TI  - Brief Challenges on Medicinal Plants: An Eye-Opening Look at Ageing-Related
      Disorders.
AB  - Several studies have reported that nature-derived antioxidants may prevent free
      radicals over-production and therefore control the onset and prevent the
      exacerbation of different kinds of diseases caused by oxidative stress and redox
      derived stressors, including ageing, fundamentally by suppressing the oxidative
      by-products-mediated degradation. Naturally derived antioxidants exert their anti
      ageing action via a panoply of signalling systems, many of which engaging
      reactive oxygen and nitrogen species scavenging, with the Nrf2/Keap1-ARE system
      and improving the many survival genes and functions (such as the pathway
      mTOR/Foxo/SIRT1) able to slow cellular senescence. Most of the research in this
      field has evaluated the regulative effects and even pathways of herbal extracts
      with antioxidant property in the ageing process, and various age-related
      disorders such as cardiovascular disease, ischaemia-reperfusion injury, coronary
      and myocardial circulatory perfusion, peripheral vascular resistance, and even
      neurodegenerative disorders are prevented plant phytochemicals often via their
      antioxidant potential. A much more complex ability to interact with survival
      functions makes these compounds successfully active in preventing ageing-related
      disorders. This report aimed to discuss in more detail some selected medicinal
      plants including Allium sativum, Aloe vera, Crataegus spp., Cynara scolymus,
      Eleutherococcus senticosus, Ginkgo biloba, Hippophae rhamnoides, Panax ginseng,
      Rosmarinus officinalis, Schizandra chinensis, Vitis vinifera and seaweeds in the
      prevention of ageing-related pathologies. A systematic overview of the relevant
      information in the antioxidant function of the many herbal products reviewed here
      for the control of the ageing process is proposed, to provide a new horizon on
      the design of anti-ageing herbal medicines.

PMID- 29369522
TI  - Uncovering cell type-specific complexities of gene expression and RNA metabolism
      by TU-tagging and EC-tagging.
AB  - Cell type-specific transcription is a key determinant of cell fate and function.
      An ongoing challenge in biology is to develop robust and stringent biochemical
      methods to explore gene expression with cell type specificity. This challenge has
      become even greater as researchers attempt to apply high-throughput RNA analysis
      methods under in vivo conditions. TU-tagging and EC-tagging are in vivo
      biosynthetic RNA tagging techniques that allow spatial and temporal specificity
      in RNA purification. Spatial specificity is achieved through targeted expression
      of pyrimidine salvage enzymes (uracil phosphoribosyltransferase and cytosine
      deaminase) and temporal specificity is achieved by controlling exposure to
      bioorthogonal substrates of these enzymes (4-thiouracil and 5-ethynylcytosine).
      Tagged RNAs can be purified from total RNA extracted from an animal or tissue and
      used in transcriptome profiling analyses. In addition to identifying cell type
      specific mRNA profiles, these techniques are applicable to noncoding RNAs and can
      be used to measure RNA transcription and decay. Potential applications of TU
      tagging and EC-tagging also include fluorescent RNA imaging and selective
      definition of RNA-protein interactions. TU-tagging and EC-tagging hold great
      promise for supporting research at the intersection of RNA biology and
      developmental biology. This article is categorized under: Technologies > Analysis
      of the Transcriptome.

PMID- 29369523
TI  - Junction-Controlled Topological Polymerization.
AB  - Methodology that enables the controlled synthesis of linear and branched polymers
      from an identical monomer will be a novel pathway for polymer synthesis and
      processing. Herein we first describe the control of one or both of the C(3)-C(3')
      and C(6)-C(6') coupling reactions of carbazolyl. In a second approach, an
      identical monomer containing two carbazolyls is polymerized using chemical and
      electrochemical oxidizers, leading to topologically controllable growth of linear
      polymers in weak oxidizer or of cross-linked polymer chains in strong oxidizer,
      with satisfactory long chain propagation of step growth polymerization (Mn
      =6.0*104  g mol-1 , Mw /Mn =2.3). This very simple polymerization with cheap
      reagents and low levels of waste has provided a flexible pathway for synthesis
      and processing of polymers.

PMID- 29369524
TI  - OPP Labeling Enables Total Protein Synthesis Quantification in CHO Production
      Cell Lines at the Single-Cell Level.
AB  - Accurate measurement of global and specific protein synthesis rates is becoming
      increasingly important, especially in the context of biotechnological
      applications such as process modeling or selection of production cell clones.
      While quantification of total protein translation across whole cell populations
      is easily achieved, methods that are capable of tracking population dynamics at
      the single-cell level are still lacking. To address this need, we apply O
      propargyl-puromycin (OPP) labeling to assess total protein synthesis in single
      recombinant Chinese hamster ovary (CHO) cells by flow cytometry. Thereby we
      demonstrate that global protein translation rates slightly increase with
      progression through the cell cycle during exponential growth. Stable CHO cell
      lines producing recombinant protein display similar levels of total protein
      synthesis as their parental CHO host cell line. Global protein translation does
      not correlate with intracellular product content of three model proteins, but the
      host cell line with high transient productivity has a higher OPP signal. This
      indicates that production cell lines with increased overall protein synthesis
      capacity can be identified by our method at the single-cell level. In conclusion,
      OPP-labeling allows rapid and reproducible assessment of global protein synthesis
      in single CHO cells, and can be multiplexed with DNA staining or any type of
      immunolabeling of specific proteins or markers for organelles.

PMID- 29369525
TI  - Biologic mechanisms and clinical consequences of pregnancy alloimmunization.
AB  - Alloimmunization occurs during pregnancy when tissue antigens derived from the
      fetus and/or placenta prime maternal immune cells to divide and differentiate.
      For many women, the result of pregnancy alloimmunization is the formation of anti
      HLA antibody that can endure for decades and preclude transplantation by limiting
      donor compatibility. Pregnancy alloimmunization may also generate memory B cells
      that can rapidly produce anti-HLA antibody after transplantation as well as
      pathogenic memory T cells, which pose a threat to graft survival. However,
      emerging data suggest that pregnancy also programs the differentiation of
      anergic, dysfunctional, and regulatory T cell populations, which may not mediate
      accelerated graft rejection. Hence, some of the immune mechanisms responsible for
      maternal immunologic tolerance of the fetus may persist into postpartum life and
      affect the response to an allograft. This review discusses these emerging data as
      well as the persistent knowledge gaps that affect women at multiple stages of
      their transplant care.

PMID- 29369526
TI  - Generative models for clinical applications in computational psychiatry.
AB  - Despite the success of modern neuroimaging techniques in furthering our
      understanding of cognitive and pathophysiological processes, translation of these
      advances into clinically relevant tools has been virtually absent until now.
      Neuromodeling represents a powerful framework for overcoming this translational
      deadlock, and the development of computational models to solve clinical problems
      has become a major scientific goal over the last decade, as reflected by the
      emergence of clinically oriented neuromodeling fields like Computational
      Psychiatry, Computational Neurology, and Computational Psychosomatics. Generative
      models of brain physiology and connectivity in the human brain play a key role in
      this endeavor, striving for computational assays that can be applied to
      neuroimaging data from individual patients for differential diagnosis and
      treatment prediction. In this review, we focus on dynamic causal modeling (DCM)
      and its use for Computational Psychiatry. DCM is a widely used generative
      modeling framework for functional magnetic resonance imaging (fMRI) and magneto
      /electroencephalography (M/EEG) data. This article reviews the basic concepts of
      DCM, revisits examples where it has proven valuable for addressing clinically
      relevant questions, and critically discusses methodological challenges and recent
      methodological advances. We conclude this review with a more general discussion
      of the promises and pitfalls of generative models in Computational Psychiatry and
      highlight the path that lies ahead of us. This article is categorized under:
      Neuroscience > Computation Neuroscience > Clinical Neuroscience.

PMID- 29369527
TI  - Anti-inflammatory medication following cataract surgery: a randomized trial
      between preservative-free dexamethasone, diclofenac and their combination.
AB  - PURPOSE: To examine the anti-inflammatory efficacy and tolerance between
      preservative-free dexamethasone (DEX) and diclofenac (DICL) eye drops, and their
      combination following cataract surgery. METHODS: A randomized, double-blind,
      prospective single-centre study with 189 eyes of 180 patients undergoing routine
      cataract surgery. Laser flare meter measurement and spectral-domain optical
      coherence tomography imaging were conducted before surgery and at the 28-day
      postoperative visit. Clinical characteristics, surgical parameters and assessment
      of postoperative symptoms were recorded. RESULTS: Preoperative flare was 9.0 +/-
      0.6 pu/ms and central retinal thickness (CRT) 269.6 +/- 1.9 MUm (mean +/- SEM).
      On day 28, flare was 22.1 +/- 2.9 pu/ms for DEX, 17.4 +/- 2.5 pu/ms for DICL and
      13.0 +/- 1.6 pu/ms (p < 0.05) for their combination. Central retinal thickness
      (CRT) increase was 31.5 +/- 8.8 MUm for DEX, 6.0 +/- 0.8 MUm (p = 0.001) for
      DICL, and 3.5 +/- 0.5 MUm (p < 0.001) for their combination. The incidence of
      ocular symptoms related to the eye drops was 11% for DEX, 37% for DICL and 34%
      for their combination (p < 0.001). Clinically significant pseudophakic cystoid
      macular oedema (PCME) was observed in seven eyes which were all treated with DEX
      (p < 0.001). CONCLUSION: Diclofenac (DICL), as well as the combination of DEX and
      DICL, were superior to DEX monotherapy in minimizing CRT change and the incidence
      of PCME. Combination medication showed no added value compared to DICL
      monotherapy in uneventful cataract surgery.

PMID- 29369529
TI  - Diabetes and branched-chain amino acids: What is the link?
AB  - Branched-chain amino acids (BCAA) have increasingly been studied as playing a
      role in diabetes, with the PubMed search string "diabetes" AND "branched chain
      amino acids" showing particular growth in studies of the topic over the past
      decade (Fig. ). In the Young Finn's Study, BCAA and, to a lesser extent, the
      aromatic amino acids phenylalanine and tyrosine were associated with insulin
      resistance (IR) in men but not in women, whereas the gluconeogenic amino acids
      alanine, glutamine, or glycine, and several other amino acids (i.e. histidine,
      arginine, and tryptophan) did not show an association with IR. Obesity may track
      more strongly than metabolic syndrome and diabetes with elevated BCAA. In a study
      of 1302 people aged 40-79; higher levels of BCAA tracked with older age, male
      sex, and metabolic syndrome, as well as with obesity, cardiovascular risk,
      dyslipidemia, hypertension, and uric acid. Medium- and long-chain acylcarnitines,
      by-products of mitochondrial catabolism of BCAAs, as well as branched-chain keto
      acids and the BCAA themselves distinguished obese people having versus not having
      features of IR, and in a study of 898 patients with essential hypertension, the
      BCAA and tyrosine and phenylalanine were associated with metabolic syndrome and
      impaired fasting glucose. In a meta-analysis of three genome-wide association
      studies, elevations in BCAA and, to a lesser extent, in alanine tracked with IR,
      whereas higher levels of glutamine and glycine were associated with lesser
      likelihood of IR. Given these associations with IR, it is not surprising that a
      number of studies have shown higher BCAA levels in people with and prior to
      development of type 2 diabetes (T2D), although this has particularly been shown
      in Caucasian and Asian ethnic groups while not appearing to occur in African
      Americans. Similarly, higher BCAA levels track with cardiovascular disease.
      [Figure: see text] The metabolism of BCAA involves two processes: (i) a
      reversible process catalysed by a branched-chain aminotransferase (BCAT), either
      cytosolic or mitochondrial, requiring pyridoxal to function as an amino group
      carrier, by which the BCAA with 2-ketoglutarate produce a branched-chain keto
      acid plus glutamate; and (ii) the irreversible mitochondrial process catalysed by
      branched-chain keto acid dehydrogenase (BCKDH) leading to formation of acetyl
      coenzyme A (CoA), propionyl-CoA, and 2-methylbutyryl-CoA from leucine, valine,
      and isoleucine, respectively, which enter the tricarboxylic acid (Krebs) cycle as
      acetyl-CoA, propionyl-CoA, and 2-methylbutyryl-CoA, respectively, leading to ATP
      formation. The BCAA stimulate secretion of both insulin and glucagon and, when
      given orally, of both glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP), with oral administration leading to greater and
      more prolonged insulin and glucagon secretion. Insulin may particularly reduce
      BCAA turnover to a greater extent than that of other amino acids, and decreases
      the appearance and increases the uptake of amino acids. However, older studies of
      the effect of glucose or insulin on BCAA concentrations and rates of leucine
      appearance and oxidation showed no reduction in T2D, although the higher baseline
      levels of BCAA in obesity have long been recognized. Impaired function of BCAT
      and BCKDH has been posited, either as a primary genetic abnormality or due to
      effects of elevated fatty acids, proinflammatory cytokines, or insulin levels
      with consequent accumulation of branched-chain keto acids and metabolites such as
      diacylglycerol and ceramide, potentially contributing to the development of
      further insulin resistance, and decreased skeletal muscle BCAT and BCKDH
      expression has been shown in people with diabetes, supporting this concept. A
      Mendelian randomization study used measured variation in genes involved in BCAA
      metabolism to test the hypothesis of a causal effect of modifiable exposure on
      IR, showing that variants in protein phosphatase, Mg2+ /Mn2+ dependent 1K
      (PPM1K), a gene encoding the mitochondrial phosphatase activating the BCKDH
      complex, are associated with T2D, but another such study suggested that genetic
      variations associated with IR are causally related to higher BCAA levels. Another
      hypothesis involves the mammalian target of rapamycin complex 1 (mTORC1), which
      is activated by BCAA, as well as by insulin and glucose via cellular ATP
      availability. If this is the relevant pathway, BCAA overload may cause insulin
      resistance by activation of mammalian target of rapamycin (mTOR), as well as by
      leading to increases in acylcarnitines, with mTOR seen in this scenario as a
      central signal of cross-talk between the BCAA and insulin. At this point, whether
      whole-body or tissue-specific BCAA metabolism is increased or decreased in states
      of insulin-resistant obesity and T2D is uncertain. Insulin action in the
      hypothalamus induces but overfeeding decreases hepatic BCKDH, leading to the
      concept that hypothalamic insulin resistance impairs BCAA metabolism in obesity
      and diabetes, so that plasma BCAAs may be markers of hypothalamic insulin action
      rather than direct mediators of changes in IR. A way to address this may be to
      understand the effects of changes in diet and other interventions on BCAA, as
      well as on IR and T2D. In an animal model, lowering dietary BCAA increased energy
      expenditure and improved insulin sensitivity. Two large human population studies
      showed an association of estimated dietary BCAA intake with T2D risk, although
      another population study showed higher dietary BCAA to be associated with lower
      T2D risk. Ethnic differences, reflecting underlying differences in genetic
      variants, may be responsible for such differences. In the study of Asghari et al.
      in the current issue of the Journal of Diabetes, BCAA intake was associated with
      the development of subsequent IR. Studies of bariatric surgery suggest lower
      basal and post-insulin infusion BCAA levels are associated with greater insulin
      sensitivity, with reductions in BCAA not seen with weight loss per se with
      gastric band procedures, but occurring after Roux-en-Y gastric bypass, an
      intervention that may have metabolic benefits over and above those from reduction
      in body weight. The gut microbiota may be important for the supply of the BCAA to
      mammalian hosts, either by de novo biosynthesis or by modifying nutrient
      absorption. A final fascinating preliminary set of observations is that of the
      effects of empagliflozin on metabolomics; evidence of increased Krebs cycle
      activation and of higher levels of BCAA metabolites, such as acylcarnitines,
      suggests that sodium-glucose cotransporter 2 (SGLT2) inhibition may, to some
      extent, involve BCAA metabolism. Certainly, we do not yet have a full
      understanding of these complex associations. However, the suggestion of multiple
      roles of BCAA in the development of IR promises to be important and to lead to
      the development of novel effective T2D therapies.

PMID- 29369528
TI  - Chromatin modifications in metabolic disease: Potential mediators of long-term
      disease risk.
AB  - Metabolic diseases such as obesity and diabetes are complex diseases resulting
      from multiple genetic and environmental factors, such as diet and activity
      levels. These factors are well known contributors to the development of metabolic
      diseases. One manner by which environmental factors can influence metabolic
      disease progression is through modifications to chromatin. These modifications
      can lead to altered gene regulatory programs, which alters disease risk.
      Furthermore, there is evidence that parents exposed to environmental factors can
      influence the metabolic health of offspring, especially if exposures are during
      intrauterine growth periods. In this review, we outline the evidence that
      chromatin modifications are associated with metabolic diseases, including
      diabetes and obesity. We also consider evidence that these chromatin
      modifications can lead to long-term disease risk and contribute to disease risk
      for future generations. This article is categorized under: Biological Mechanisms
      > Metabolism Developmental Biology > Developmental Processes in Health and
      Disease Physiology > Organismal Responses to Environment.

PMID- 29369530
TI  - Ophthalmological data on 4.5- to 7-year-old Danish children.
AB  - PURPOSE: To report normative data on visual acuity (VA) for near and distance,
      refraction, ocular alignment, ocular motility and stereo acuity in a cohort of
      children aged 4.5-7 years. METHODS: A total of 950 children with normal
      development from the municipality of Roskilde, Denmark, were invited to
      participate in an ophthalmic cross-sectional population-based survey, of which
      445 children in the age of 54-87 months participated with a complete ocular
      examination including cycloplegia. Visual acuity (VA) was tested using Kay
      Picture charts and notified in logMAR units. RESULTS: Mean distance VA was 0.010
      logMAR [standard deviation (SD): 0.048] in right eye, and near VA in right eye
      was 0.012 logMAR (SD: 0.054), with a nonsignificant difference between right and
      left eye in both parameters (paired t-test, p = 0.15 and p = 0.08, respectively).
      Amblyopia was found in 12 children (2.7%), mainly related to refractive errors.
      The mean refractive error of right eye was +1.75 D, and significant hyperopia
      (greater than +3.0 D) was found in 7.9%. No myopia (greater than or equal to -0.5
      D) was found, astigmatism (>1 D) was seen in 4.3%. Manifest strabismus was
      present in 1.6%, and heterophoria in 4.0%. Reduced or absent stereo acuity was
      present in 35 children (7.9%) and was related to a reduced VA, refractive error
      and strabismus. CONCLUSION: Ophthalmic data of 445 normally developed children
      are presented, supplementing previous reported normative data in children. We
      found a relatively high prevalence of amblyopia and of hyperopia, while myopia
      was not found, confirming previous studies that myopia is not developing at early
      age in Danish children.

PMID- 29369531
TI  - Enterohaemorrhagic and other Shiga toxin-producing Escherichia coli (STEC): Where
      are we now regarding diagnostics and control strategies?
AB  - Escherichia coli comprises a highly diverse group of Gram-negative bacteria and
      is a common member of the intestinal microflora of humans and animals. Generally,
      such colonization is asymptomatic; however, some E. coli strains have evolved to
      become pathogenic and thus cause clinical disease in susceptible hosts. One
      pathotype, the Shiga toxigenic E. coli (STEC) comprising strains expressing a
      Shiga-like toxin is an important foodborne pathogen. A subset of STEC are the
      enterohaemorrhagic E. coli (EHEC), which can cause serious human disease,
      including haemolytic uraemic syndrome (HUS). The diagnosis of EHEC infections and
      the surveillance of STEC in the food chain and the environment require accurate,
      cost-effective and timely tests. In this review, we describe and evaluate tests
      now in routine use, as well as upcoming test technologies for pathogen detection,
      including loop-mediated isothermal amplification (LAMP) and whole-genome
      sequencing (WGS). We have considered the need for improved diagnostic tools in
      current strategies for the control and prevention of these pathogens in humans,
      the food chain and the environment. We conclude that although significant
      progress has been made, STEC still remains an important zoonotic issue worldwide.
      Substantial reductions in the public health burden due to this infection will
      require a multipronged approach, including ongoing surveillance with high
      resolution diagnostic techniques currently being developed and integrated into
      the routine investigations of public health laboratories. However, additional
      research requirements may be needed before such high-resolution diagnostic tools
      can be used to enable the development of appropriate interventions, such as
      vaccines and decontamination strategies.

PMID- 29369532
TI  - Increased endothelin-1-mediated vasoconstriction after organ culture in rat and
      pig ocular arteries can be suppressed with MEK/ERK1/2 inhibitors.
AB  - PURPOSE: Even though retinal vascular changes following ischaemia have been
      poorly understood, the upregulation of vasoconstrictive endothelin-1 (ET-1)
      receptors (ETA /ETB ) following global cerebral ischaemia has been described. The
      aim of this study was to investigate whether or not the MEK/ERK1/2 pathway is
      involved in the observed upregulation and whether specific MEK/ERK1/2 inhibitors
      U0126 and trametinib can prevent it. METHODS: The aim was also to localize ETA
      and ETB receptors using immunohistochemistry in both fresh rat ophthalmic
      arteries and after 24-hr organ culture and study the receptors functionally using
      myography. Pig retinal arteries also underwent 24-hr organ culture to validate
      similar responses across species and the retinal vasculature. RESULTS: Results
      showed that following organ culture there is a significant increase in ET-1
      mediated vasoconstriction, in particular via the ETB receptor. Furthermore,
      immunohistochemistry revealed a clear increase in pERK in the smooth muscle cells
      of rat ophthalmic artery. U0126 and trametinib were successful in attenuating the
      functional vasoconstriction in both rat and pig, as well as restoring
      immunofluorescence of pERK to fresh levels and counteracting ETB expression in
      the smooth muscle cells of the rat ophthalmic artery. CONCLUSION: This is the
      first study to show that the MEK/ERK1/2 pathway in responsible for the increase
      in functional vasoconstriction via ET-1 receptor in rat ophthalmic and pig
      retinal arteries. Furthermore, this study is the first to suggest a way of
      inhibiting and preventing such an increase. With these results, we suggest a
      novel approach in retinal ischaemia therapy.

PMID- 29369533
TI  - Slowly progressive unilateral retinal pigment epithelium dysgenesis leading to
      severe visual impairment.

PMID- 29369534
TI  - Autoimmunity in uveitis.
AB  - PURPOSE: Recent insights into the pathogenesis of immune-mediated diseases
      proposed a new classification, which includes autoimmune and auto-inflammatory
      diseases. The prevalence of specific autoimmune and auto-inflammatory diseases in
      uveitis and/or scleritis is not yet known. In this study, we examine the presence
      of systemic immune-mediated diseases in patients with uveitis and/or scleritis
      and put a special emphasis on autoimmune disorders by reporting on their clinical
      manifestations and visual prognosis. METHODS: In this retrospective study, we
      reviewed data of 1327 patients presenting with uveitis and/or scleritis between
      January 2010 and July 2016 at the Erasmus Medical Center, Rotterdam, the
      Netherlands. All patients with noninfectious uveitis and/or scleritis were
      classified according to novel criteria for immune-mediated diseases. Various
      clinical data, including visual acuity (VA), of patients with uveitis of
      autoimmune origin were registered during 5-year follow-up. RESULTS: The origin of
      uveitis was in 5% (62/1327) autoimmune, in 15% (197/1327) auto-inflammatory and
      in 14% (180/1327) mixed autoimmune/auto-inflammatory. Patients with classical
      autoimmune connective tissue disease (N = 17) suffered mostly from rheumatoid
      arthritis and granulomatosis with polyangiitis and exhibited predominantly
      scleritis (53%). After 5 years of follow-up, none of the eyes of these patients
      developed legal blindness (VA of <0.1). The VA in patients with uveitis
      associated with autoimmune neuro-ophthalmological diseases (multiple sclerosis
      and neuromyelitis optica; N = 27) remained stable over time. CONCLUSION: Uveitis
      and scleritis of autoimmune origin were observed in 5% of the total series. The
      term autoimmune uveitis should not be used as a synonym for intraocular
      inflammation of noninfectious origin.

PMID- 29369535
TI  - Long-term uveal and capsular biocompatibility of a novel modular intraocular lens
      system.
AB  - BACKGROUND: We evaluated the long-term biocompatibility and safety of a new
      modular posterior chamber intraocular lens (IOL) system in rabbit eyes. METHODS:
      Seven New Zealand rabbits underwent bilateral phacoemulsification with placement
      of the modular IOL in OD and a control IOL (SA60AT) in OS. Slit-lamp examinations
      were performed at postoperative weeks 1, 2, 3, 4, 6 and 8 and months 3 and 6. All
      rabbits were then sacrificed and eyes enucleated. The eyes were examined grossly
      from the Miyake-Apple view. Selected IOLs were explanted and underwent surface
      staining for implant cytology. All globes were then sectioned and processed for
      histopathological examination. RESULTS: The modular IOL remained stable in all
      seven rabbits through the entire follow-up period. Biocompatibility was better
      than the control lens at six months postoperatively, on account of less extensive
      synechiae formation as assessed by slit-lamp examination. At the six-week
      examination, posterior capsule opacification (PCO) was significantly better in
      the test group (scored as 1.71 +/- 0.8 versus 3.28 +/- 0.48 in the control group,
      p = 0.0008). On gross examination with the Miyake-Apple view, Soemmering's ring
      formation was significantly better in the test group, (5.14 +/- 1.57 versus 10.85
      +/- 1.95 in the control group, p = 0.002). CONCLUSION: Previous studies showed
      that explantation/exchange of the modular system optic was safer and easier than
      with a standard IOL. The new modular IOL system has demonstrated better long-term
      biocompatibility compared to the control lens at six months postoperatively in
      the rabbit model.

PMID- 29369536
TI  - Systems biology of embryonic development: Prospects for a complete understanding
      of the Caenorhabditis elegans embryo.
AB  - The convergence of developmental biology and modern genomics tools brings the
      potential for a comprehensive understanding of developmental systems. This is
      especially true for the Caenorhabditis elegans embryo because its small size,
      invariant developmental lineage, and powerful genetic and genomic tools provide
      the prospect of a cellular resolution understanding of messenger RNA (mRNA)
      expression and regulation across the organism. We describe here how a systems
      biology framework might allow large-scale determination of the embryonic
      regulatory relationships encoded in the C. elegans genome. This framework
      consists of two broad steps: (a) defining the "parts list"-all genes expressed in
      all cells at each time during development and (b) iterative steps of
      computational modeling and refinement of these models by experimental
      perturbation. Substantial progress has been made towards defining the parts list
      through imaging methods such as large-scale green fluorescent protein (GFP)
      reporter analysis. Imaging results are now being augmented by high-resolution
      transcriptome methods such as single-cell RNA sequencing, and it is likely the
      complete expression patterns of all genes across the embryo will be known within
      the next few years. In contrast, the modeling and perturbation experiments
      performed so far have focused largely on individual cell types or genes, and
      improved methods will be needed to expand them to the full genome and organism.
      This emerging comprehensive map of embryonic expression and regulatory function
      will provide a powerful resource for developmental biologists, and would also
      allow scientists to ask questions not accessible without a comprehensive picture.
      This article is categorized under: Invertebrate Organogenesis > Worms
      Technologies > Analysis of the Transcriptome Gene Expression and Transcriptional
      Hierarchies > Gene Networks and Genomics.

PMID- 29369537
TI  - Evaluation of an individualized dose titration regimen of patiromer to prevent
      hyperkalaemia in patients with heart failure and chronic kidney disease.
AB  - AIMS: Hyperkalaemia risk precludes optimal renin-angiotensin-aldosterone system
      inhibitor use in patients with heart failure (HF), particularly those with
      chronic kidney disease (CKD). Patiromer is a sodium-free, non-absorbed potassium
      (K+ )-binding polymer approved for the treatment of hyperkalaemia. In PEARL-HF,
      patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or
      without CKD initiating spironolactone. The current study evaluated the
      effectiveness of a lower starting dose of patiromer (16.4 g/day) followed by
      individualized titration in preventing hyperkalaemia and hypokalaemia when
      initiating spironolactone. METHODS AND RESULTS: This open-label 8-week study
      enrolled 63 patients with CKD, serum K+ 4.3-5.1 mEq/L, and chronic HF, who, based
      on investigator opinion, should receive spironolactone. Eligible patients started
      spironolactone 25 mg/day and patiromer 16.8 g/day (divided into two doses), with
      patiromer titrated to maintain serum K+ 4.0-5.1 mEq/L. Mean (standard deviation)
      serum K+ was 4.78 (0.51) mEq/L at baseline; weekly values were 4.48-4.70 mEq/L
      during treatment. Serum K+ of 3.5-5.5 mEq/L at the end of study treatment
      (primary endpoint) was achieved by 57 (90.5%) patients; 53 (84.1%) had serum K+
      4.0-5.1 mEq/L. One patient (1.6%) developed hypokalaemia, and two patients (3.2%)
      developed hypomagnesaemia. Spironolactone was increased to 50 mg/day in all
      patients; 43 (68%) patients required one or more patiromer dose titration.
      Adverse events (AEs) occurred in 36 (57.1%) patients, with a low rate of
      discontinuations [four (6.3%) patients]. The most common AE was mild to moderate
      abdominal discomfort [four (6.3%) patients]. CONCLUSIONS: In this open-label
      study, patiromer 16.8 g/day followed by individualized titration maintained serum
      K+ within the target range in the majority of patients with HF and CKD, all of
      whom were uptitrated to spironolactone 50 mg/day, patiromer was well tolerated,
      with a low incidence of hyperkalaemia, hypokalaemia, and hypomagnesaemia.

PMID- 29369539
TI  - Well-Controlled Cell-Trapping Systems for Investigating Heterogeneous Cell-Cell
      Interactions.
AB  - Microfluidic systems have been developed for patterning single cells to study
      cell-cell interactions. However, patterning multiple types of cells to understand
      heterogeneous cell-cell interactions remains difficult. Here, it is aimed to
      develop a cell-trapping device to assemble multiple types of cells in the well
      controlled order and morphology. This device mainly comprises a parylene sheet
      for assembling cells and a microcomb for controlling the cell-trapping area. The
      cell-trapping area is controlled by moving the parylene sheet on an SU-8
      microcomb using tweezers. Gentle downward flow is used as a driving force for the
      cell-trapping. The assembly of cells on a parylene sheet with round and line
      shaped apertures is demonstrated. The cell-cell contacts of the trapped cells are
      then investigated by direct cell-cell transfer of calcein via connexin nanopores.
      Finally, using the device with a system for controlling the cell-trapping area,
      three different types of cells in the well-controlled order are assembled. The
      correct cell order rate obtained using the device is 27.9%, which is higher than
      that obtained without the sliding parylene system (0.74%). Furthermore, the
      occurrence of cell-cell contact between the three cell types assembled is
      verified. This cell-patterning device will be a useful tool for investigating
      heterogeneous cell-cell interactions.

PMID- 29369538
TI  - Long-term uveal melanoma survivors: measuring their quality of life.
AB  - PURPOSE: Patients with uveal melanoma (UM) undergo lifelong follow-up as
      metastases can occur more than 20 years after diagnosis. Little is known about
      the quality of life (QoL) of UM survivors over such an extended period. To
      investigate their QoL, we used various estimating factors. METHODS: A cohort of
      patients diagnosed and treated for UM with regularly scheduled follow-up visits
      was asked to fill in a European Organization for Research and Treatment of Cancer
      (EORTC) questionnaire comprised of the EORTC QLQ-C30 and EORTC QLQ-OPT30 modules.
      An additional open question examined other changes in the patients' lifestyle
      since diagnosis. Independent demographic and medical data were collected from
      patient records. RESULTS: Two hundred and thirty-two of 294 patients agreed to
      complete the questionnaire. General QoL correlated highly with the eye-related
      QoL. Statistically significant higher QoL was associated with tumours not
      involving the ciliary body, and with better best-corrected visual acuity (BCVA).
      A subgroup of 39% of the patients reported severe disability affecting eye
      related tasks. Thirty-three per cent were highly concerned about various aspects
      of their future health. Patients who underwent enucleation reported lower eye
      related QoL and described problems related to body image in response to the open
      question. CONCLUSION: General QoL of UM patients is only slightly affected by
      their malignancy. However, body image and psychosocial adjustment are major
      issues involved in evaluating QoL. Continuous long-term psychosocial treatment is
      needed from the time of diagnosis in a subgroup of patients suffering from eye
      related disabilities.

PMID- 29369540
TI  - Electron microscopic findings of an explanted retropupillary Artisan lens 3 years
      after implantation.

PMID- 29369541
TI  - Hierarchical Design of Tissue Regenerative Constructs.
AB  - The worldwide shortage of organs fosters significant advancements in regenerative
      therapies. Tissue engineering and regeneration aim to supply or repair organs or
      tissues by combining material scaffolds, biochemical signals, and cells. The
      greatest challenge entails the creation of a suitable implantable or injectable
      3D macroenvironment and microenvironment to allow for ex vivo or in vivo cell
      induced tissue formation. This review gives an overview of the essential
      components of tissue regenerating scaffolds, ranging from the molecular to the
      macroscopic scale in a hierarchical manner. Further, this review elaborates about
      recent pivotal technologies, such as photopatterning, electrospinning, 3D
      bioprinting, or the assembly of micrometer-scale building blocks, which enable
      the incorporation of local heterogeneities, similar to most native extracellular
      matrices. These methods are applied to mimic a vast number of different tissues,
      including cartilage, bone, nerves, muscle, heart, and blood vessels. Despite the
      tremendous progress that has been made in the last decade, it remains a hurdle to
      build biomaterial constructs in vitro or in vivo with a native-like structure and
      architecture, including spatiotemporal control of biofunctional domains and
      mechanical properties. New chemistries and assembly methods in water will be
      crucial to develop therapies that are clinically translatable and can evolve into
      organized and functional tissues.

PMID- 29369542
TI  - Identification of Sox6 as a regulator of pancreatic cancer development.
AB  - Pancreatic cancer (PC) is an aggressive malignancy associated with a poor
      prognosis and low responsiveness to chemotherapy and radiotherapy. Most patients
      with PC have metastatic disease at diagnosis, which partly accounts for the high
      mortality from this disease. Here, we explored the role of the transcription
      factor sex-determining region Y-box (Sox) 6 in the invasiveness of PC cells. We
      showed that Sox6 is down-regulated in patients with PC in association with
      metastatic disease. Sox6 overexpression suppressed PC cell proliferation and
      migration in vitro and tumour growth and liver metastasis in vivo. Sox6 inhibited
      epithelial-mesenchymal transition (EMT), and Akt signalling. Sox6 was shown to
      interact with the promoter of Twist1, a helix-loop-helix transcription factor
      involved in the induction of EMT, and to modulate the expression of Twist1 by
      recruiting histone deacetylase 1 to the promoter of the Twist1 gene. Twist1
      overexpression reversed the effect of Sox6 on inhibiting EMT, confirming that the
      effect of Sox6 on suppressing tumour invasiveness is mediated by the modulation
      of Twist1 expression. These results suggest a novel mechanism underlying the
      aggressive behaviour of PC cells and identify potential therapeutic targets for
      the treatment of PC.

PMID- 29369543
TI  - Intravitreal diclofenac for treatment of refractory uveitis-associated cystoid
      macular oedema: A before and after clinical study.
AB  - BACKGROUND: Cystoid macular oedema (CME) is one of the important complications of
      uveitis leading to irreversible blindness. Currently, there is no gold standard
      treatment for this condition. The aim of this study was to investigate the
      effects of single intravitreal diclofenac (IVD) injection on short-term outcome
      of refractory uveitis-associated CME. METHODS: This was a prospective clinical
      study on 16 consecutive patients (16 eyes) with refractory uveitis-associated
      CME. Intravitreal injection of 500 MUg/0.1 ml of diclofenac sodium was given to
      the patients. The clinical outcomes considered were best-corrected visual acuity
      (BCVA) change and central macular thickness (CMT) changes in the pre- and
      postinjection periods. Follow-up examinations were performed at 1 and 4 weeks
      after the injection. RESULTS: Age of the patients varied from 18 to 59 years
      (mean +/- SD: 39.5 +/- 13.2 years). Ten patients (62.5%) were females.
      Statistically significant differences were found in the decrease of mean BCVA
      (logMAR) (p = 0.043) and mean CMT (p = 0.003) during the study period. There was
      no significant difference in the intraocular pressure (IOP) increase at the end
      of the study (p = 0.94). CONCLUSION: Intravitreal diclofenac (IVD) may be a
      promising treatment for refractory uveitis-associated CME. Further clinical
      trials with a larger sample size should be conducted to confirm these findings
      and compare them with other treatments.

PMID- 29369544
TI  - Turkish Adaptation of Dentine Hypersensitivity Experience Questionnaire (DHEQ).
AB  - OBJECTIVE: The Dentine Hypersensitivity Experience Questionnaire (DHEQ) is a
      valid and reliable instrument for oral health-related quality of life (OHRQoL)
      studies. This study aimed to assess the Turkish version of the DHEQ and determine
      the effects of degree of DH, sex, and age on OHRQoL. MATERIALS: The study
      participants were 251 DH patients (age 18-78 years; 68.5% female) who completed
      the Turkish version of the DHEQ. The reliability of the instrument was assessed
      in terms of internal consistency, using item-total correlations and Cronbach's
      alpha and test-retest reliability using intra-class correlation coefficients
      (ICCs) among 51 patients who repeated the DHEQ following a 2-week interval.
      Construct validity was determined based on exploratory factor analysis (EFA).
      Convergent validity was tested through correlating DHEQ total and subscale scores
      with the global rating of oral health and effect on life overall. Discriminative
      validity was tested by comparing the total and subscale scores against the degree
      of sensitivity. RESULTS: Patients with more severe hypersensitivity showed higher
      DHEQ scores and greater OHRQoL impairment. Female and older (?40 years) patients
      had significantly greater OHRQoL impairment. Cronbach's alpha exceeded 0.70,
      indicating good internal consistency reliability. The ICC values measured were
      ?0.60 for the overall scale and each subscale of the DHEQ, signifying good to
      excellent test-retest reliability. CONCLUSION: The results suggested that the
      Turkish version of the DHEQ is appropriate for assessing the OHRQoL among people
      with dentine hypersensitivity.

PMID- 29369545
TI  - Illness perceptions amongst individuals with dental caries.
AB  - OBJECTIVE: To assess individuals' perception of dental caries, in order to
      explain how illness representations might influence their coping with the
      disease. METHODS: Cross-sectional questionnaire study. PARTICIPANTS: 520
      consecutive patients (aged >=18 years) of the General Dentistry Clinic at
      Universidad Cooperativa de Colombia, Pasto, Colombia who had experienced dental
      caries. MAIN OUTCOME MEASURES: Illness perception of dental caries was assessed
      using the Illness Perception Questionnaire Revised (IPQ-R). RESULTS: The most
      frequent self-reported symptoms associated with dental caries were "toothache"
      (56.2%), "tooth sensitivity" (53.8%) and "mild to sharp pain when eating or
      drinking" (51.2%). The dimensions of illness perception were related to socio
      economic status (SES). Symptoms of "loose or separating teeth" and "pus in your
      tooth" were associated with dental caries by low SES participants, while
      "bleeding while brushing, flossing or eating hard food" and "mild to sharp pain
      when eating or drinking something sweet, hot or cold" were related more to higher
      SES. CONCLUSIONS: Perceptions of caries were related to socioeconomic status.
      Interventions to promote health literacy in order to improve the capacity to
      obtain, process and understand basic oral health information could increase an
      early detection of caries.

PMID- 29369546
TI  - The use of cost-utility analysis for the evaluation of caries prevention: an
      exploratory case study of two community-based public health interventions in a
      high-risk population in the UK.
AB  - BACKGROUND: Economic evaluations are important tools for decision makers to
      determine the best allocation of resources in a healthcare system. This study
      explored the use of economic evaluation in oral health promotion. METHODS: A
      literature review identified oral health promotion programmes that measured both
      the health impact and costs of oral health interventions. A decision analysis
      model was constructed to examine the cost utility of preventing dental caries in
      5 and 12-year-old children via tooth brushing schemes and fluoride varnish
      programmes. The costs per child that would be justified according to the National
      Institute for Health and Care Excellence's threshold of L20,000 per QALY were
      calculated. RESULTS: The analysis showed that NICE would consider that the
      expenditure of L55 per child on supervised tooth brushing, or L100 per child on
      fluoride varnish application would give sufficient health benefits to be
      justified according to their threshold. CONCLUSIONS: Greater attention needs to
      be paid to the collection of robust data on costs for oral health promotion.
      Dental researchers also urgently need to collect outcome data in a form that can
      be translated into a Quality of Life measure, so that the true cost effectiveness
      and value for money achieved through the prevention of dental disease can be
      recognised and compared to other allocations of resource.

PMID- 29369547
TI  - Recall intervals and time used for examination and prevention by dentists in
      child dental care in Denmark, Iceland, Norway and Sweden in 1996 and 2014.
AB  - OBJECTIVE: The purpose of the present study was to explore intervals between
      regular dental examination and the time dentists spent for examination and
      preventive dental care of children in 1996 and 2014. PARTICIPANTS AND METHODS: In
      Denmark, Norway and Sweden, random samples of dentists working with children were
      included, while in Iceland all dentists were mailed questionnaires. Complete
      information was provided by 1082 of 1834 dentists (64%) in 1996 and 1366 of 2334
      dentists (59%) in 2014. Results were assessed using chi-square and analysis of
      variance with post-hoc tests. RESULTS: Some trends were consistent in all
      countries, but considerable differences in routines between the countries
      persisted during the period. The most used and maximum planned recall intervals
      were on average 14.8 (sd 4.8) and 18.5 (sd 4.6) months in 2014, respectively 3.1
      and 3.5 months longer than in 1996 (p?0.05). In 2014 dentists used ample time
      delivering preventive care to children. Dentists reported spending significantly
      more time providing preventive care for caries risk children than for other
      children both in 1996 and 2014. Concurrent with extended intervals, dentists
      reported spending longer performing routine examinations in three of the four
      countries in 2014 than in 1996. CONCLUSIONS: This study of trends in dental care
      delivered by dentists during recent decades showed moves towards extended recall
      intervals and preventive care individualized according to caries risk. In
      addition, extending intervals could necessitate more time for a routine dental
      examination.

PMID- 29369548
TI  - [Association of gene polymorphisms of matrix metalloproteinases with reproductive
      losses in the first trimester of pregnancy].
AB  - In the present study, the frequencies of genotypes and alleles of candidate genes
      with respect to polymorphisms associated with increased pregnancy loss in the
      first trimester of pregnancy, including MMP1-1607insG, MMP9 A-8202G, and TIMP1
      S536T, were reported. The frequency of homozygotes for allele MMP9 A-8202 was
      increased by a factor of two among women with miscarriage in the first trimester
      compared to the control. Significant models of interaction of genes MMPs and
      TIMP1 were revealed. The genotypes of genes MMP1 (rs1799750), MMP9 (rs11697325),
      and TIMP1 (rs11551797) increasing the risk of pregnancy loss in the first
      trimester were determined.

PMID- 29369549
TI  - [Association of polymorphic markers of chemokine genes, their receptors, and CD14
      gene with coronary atherosclerosis].
AB  - Atherosclerosis represents an inflammatory response to the disturbance of the
      endothelial layer in the arterial bloodstream. In the present study, an analysis
      of associations of polymorphic markers for the genes controlling synthesis of
      proteins involved in atherosclerosis pathogenesis in coronary atherosclerosis
      (CA) patients (217 subjects) and in a control group (250 subjects) was conducted.
      The following genes were examined: rs991804 (CCL2 gene), rs1126579 (CXCR2 gene),
      rs4074 (CXCL1 gene), rs4073 (CXCL8 gene), rs333 (CCR5 gene), rs2471859 (CXCR4
      gene), rs1801157 (CXCL12 gene), and rs2569190 (CD14 gene). Using the Monte Carlo
      and Markov chain (APSampler) method, allele/genotype combinations associated with
      both low and high CA risk were revealed. The most important findings included the
      following: CXCR4*T/T + CCL2*C + CCR5*I/I (P perm = 1 * 10-6, OR = 0.44, 95% CI
      0.3-0.63), CXCR2*C + CD14*C + CXCL12*G + CCL2*C + CCR5*D (P perm = 4 * 10-6, OR =
      5.78, 95% CI 2.34-14.28), CD14*C + CCL2*C/C + CCR5*D (P perm = 6.3 * 10-6, OR =
      5.81, 95% CI 2.17-15.56), CXCL8*A + CXCR2*C + CD14*T + CXCR4*C (P perm = 0.01, OR
      = 3.21, 95% CI 1.63-6.31).

PMID- 29369550
TI  - [Manifestation of multimodality in a simple ecological-genetic model of
      population evolution].
AB  - An investigation of the nature of dynamics of the population size and genetic
      structure is carried out for a homogeneous ecologically limited population
      influenced by density-dependent r-K selection in a single diallelic genetic
      locus. The detailed study of the results of basic types of natural selection is
      carried out with additional consideration of the influence of initial conditions.
      It is shown that coexistence of several different asymptotic dynamic modes (with
      their own attraction basins) is possible in numerous enough parametric domains
      which are meaningful biologically.

PMID- 29369551
TI  - A Smart Detection System Based on Specific Magnetic and Rolling Cycle
      Amplification Signal-Amplified Dual-Aptamers to Accurately Monitor Minimal
      Residual Diseases in Patients with T-ALL.
AB  - It is a major clinical challenge for clinicians how to early find out minimal
      residual diseases (MRD) of leukemia. Here, we developed a smart detection system
      for MRD involving magnetic aptamer sgc8 probe (M-sgc8 probe) to capture CEM cells
      and rolling cycle amplification probe (RCA-sgc8 probe) to initiate RCA, producing
      a single-stranded tandem repeated copy of the circular template. The DNA products
      were hybridized with molecular beacon to generate the amplified fluorescence
      signal. An in vitro model to mimic MRD was established to evaluate the
      sensitivity of the smart detection system. The smart detection system was used to
      detect MRD in patients with T-ALL peri-chemotherapy, which could not only
      specifically captured T-ALL cells, but also significantly amplified fluorescence
      signals on them. The sensitivity was 1/20,000. These results indicate that the
      smart detection system with high specificity and sensitivity could more
      efficiently monitor the progress of T-ALL peri-chemotherapy.

PMID- 29369552
TI  - [Association of variable rs1801282 locus of PPARG2 gene with diabetic
      nephropathy].
AB  - The association of the variable rs1801282 locus of the PPARG2 gene (peroxisome
      proliferator-activated receptor gamma) with type 2 diabetes mellitus and its
      complications was analyzed in inhabitants of the Republic of Bashkortostan. The
      genotype frequencies of the variable rs1801282 locus of the PPARG2 gene did not
      significantly differ in groups of healthy persons and patients with type 2
      diabetes in all three considered inheritance models (codominant, dominant, and
      recessive). At the same time, it was demonstrated that the risk of one of the
      diabetic complications, i.e., diabetic nephropathy, was associated with the
      variable rs1801282 locus of the PPARG2 gene. Diabetic nephropathy was more common
      in patients with the C/C genotype (62.7%) compared to the C/G and G/G genotypes
      (37.5%), P = 0.036. The G allele is protective in regard to diabetic nephropathy
      (OR = 0.36) in patients with type 2 diabetes mellitus.

PMID- 29369553
TI  - [Inheritance of longitudinal white shell bands in the snail Littorina obtusata
      (Gastropoda, Prosobranchia)].
AB  - The hypothesis on monogenic inheritance of white longitudinal shell bands in the
      snail Littorina obtusata was tested. The data showed that a single gene with two
      alleles was responsible for the presence of the bands on the snail shell. The
      presence of bands was the dominant character.

PMID- 29369554
TI  - [Erratum to: "A comparative analysis of methylation status of tumor suppressor
      genes in paired biopsy and serum samples from cervical cancer patients among
      North Indian population"].

PMID- 29369555
TI  - [Breeding of the Russian sable: Stages of industrial domestication and genetic
      variability].
AB  - Creating farms for sable breeding was associated with the commercial destruction
      of natural populations and, consequently, the overall decline in the species
      number. The gene pool of the first farm-bred sable population in Russia,
      established in the vicinity of Moscow ("Pushkinskiy" fur farm), was formed by
      crossing of animals removed from nine natural populations. In the first eight
      years of farm operation, approximately one thousand animals were used for sable
      breeding; some of these animals were able to adapt to the farm management and,
      subsequently, to the selection for a number of quantitative traits in the period
      of industrial domestication. It took about ten years for breeders to work out the
      breeding and selection technologies, which became successfully employed in the
      established affiliated sable breeding farms. The main achievement in sable
      breeding over the 85-year historical period of breeding in Russia is the creation
      of two unique breeds, black sable (1969) and Saltykovskaya 1 (2007). In general,
      industrial domestication in fur farming and the subsequent breeding works made
      the fur of many species (mink, fox, Arctic fox) obtained from natural populations
      uncompetitive, which undoubtedly reduced the hunting interest in the animals
      living in the wild. Consequently, hunting for fur-bearing animals of most species
      decreased and has only local importance. Owing to the specific features of sable
      biology, the fur of farm-bred animals cannot yet completely replace the furs
      obtained by hunting; however, the farm-bred sable population is constantly
      growing. This review presents the results of the analysis of the level of genetic
      variability in natural and farm populations at nuclear and mitochondrial loci.
      The comparative analysis makes it possible to estimate the loss of genetic
      diversity upon the species adaptation to the new conditions of existence.

PMID- 29369556
TI  - [Analysis of complete sequence of cryptic plasmid pTP33 from Yersinia pestis
      isolated in Tuva natural focus of plague].
AB  - This paper studies a full nucleotide sequence of cryptic plasmid pTP33, which was
      isolated from the typical plague strain of the Tuvinian natural focus, Yersinia
      pestis I-2638. Sequencing was carried out using the 454 GS Junior platform
      (Roche). In analysis using the software package GS De Novo Assembler v. 2.7
      (Roche) and the algorithm Newbler v. 2.7, 1855 nucleotide reads, which contained
      1101246 nucleotides, were assembled to a contig of 33 978 bp. The GC content of
      the obtained nucleotide sequence was 50.25%. During annotation, we found 56 open
      reading frames. Homologs of the predicted reading frames were sought in the BLAST
      databases. We detected 22 reading frames coding hypothetical proteins, 23 frames
      coding phagerelated proteins, and 11 frames coding proteins with known functions,
      including toxin-antitoxin system YefM-YoeB, nucleic acids and polysaccharides
      metabolism proteins (exopolysaccharide production protein ExoZ,
      exodeoxyribonuclease VIII), and replication proteins (ParA). Some predicted pTP33
      proteins were found to be homologs (from 45 to 75%) with sequences of phage
      related proteins of certain microorganisms-endosymbionts of insects (Sodalis
      glossinidius) and endosymbionts of entomopathogenic nematodes (Photorhabdus
      luminescens, P. asymbiotica, Xenorhabdus bovienii).

PMID- 29369557
TI  - [Lactobacillus fermentum 90 TC-4 taxonomic status confirmation using whole genome
      sequencing and MALDI TOF mass spectrum].
AB  - With the use of whole genome sequencing, the taxonomic status of Lactobacillus
      fermentum 90 TC-4 strain from Russian collections were studied. Complex analysis
      of phenotypical and genetic properties was conducted using phenotypic and
      molecular genetic methods. The main characteristics of the genome and biochemical
      activity profile of the strain were determined. A comparative analysis of the
      mass spectrum of ribosomal proteins of the strain, its biochemical properties, a
      fragment of 16S rRNA gene sequencing, and the entire genome revealed that the
      present strain belongs to the species L. fermentum, confirming its taxonomic
      status in accordance with modern taxonomy.

PMID- 29369558
TI  - [Genome structure and origin of nontoxigenic strains of Vibrio cholerae of El Tor
      biovar with different epidemiological significance].
AB  - Intraspecies genetic differentiation of nontoxigenic strains of Vibrio cholerae
      of El Tor biovar containing one of the key pathogenicity genes, tcpA, is studied
      along with the phylogenetic relationships between these strains and toxigenic
      isolates. Comparative analysis of the whole genome nucleotide sequences
      demonstrates for the first time that ctxA - tcpA + strains vary considerably and
      can be clustered into two separate groups, the CTXphi-RS1phi +VPI+VSP+/CTXphi
      RS1phi-VPI+VSP+ isolates and the CTXphi-RS1phi-VPI+VSP- isolates, differing in
      their epidemiological significance. In the course of model experiments, it is
      established that nontoxigenic potentially epidemic CTXphi-RS1phi +VPI+VSP+/CTXphi
      RS1phi-VPI+VSP+ isolates are derivatives of toxigenic strains. The results of
      whole genome SNP analysis of 35 Vibrio cholerae strains confirm these data and
      indicate genetic remoteness of nontoxigenic CTXphi-RS1phi-VPI+VSP- strains both
      from the potentially epidemic strains and from the toxigenic isolates. It is
      found that the genomes of the CTXphi-RS1phi-VPI+VSP- strains contain unique SNPs
      which are characteristic of them alone. The new data on the structure of the
      genome of nontoxigenic strains with different epidemiological significance may be
      further used for their genetic differentiation.

PMID- 29369559
TI  - [Disequilibrium distribution of genotypes in the pairs of isozyme loci in the
      pine populations of the forest-steppe regions of Siberia].
AB  - We performed an analysis of linkage disequilibrium of alleles of 15 allozyme loci
      in 35 populations of Scots pine in the Siberian part of the range between 50
      degrees  and 56 degrees  N and 79 degrees  and 107 degrees  E. We found a
      significant deviation in the distribution of genotypes of 1-9 pairs of loci in
      the investigated samples. We established correlations between frequencies of
      certain pairs of linked loci with ecological conditions and geographical
      coordinates of habitats of the pine populations. We present the results of
      comparative analysis of the differences in certain morphological features of
      trees with significantly predominant genotypes for pairs of linked loci in three
      isolated populations: in the south of Krasnoyarsk krai, Khakassia, and Tuva.

PMID- 29369560
TI  - [Expression of plant antimicrobial peptide pro-SmAMP2 gene increases resistance
      of transgenic potato plants to Alternaria and Fusarium pathogens].
AB  - The chickweed (Stellaria media L.) pro-SmAMP2 gene encodes the hevein-like
      peptides that have in vitro antimicrobial activity against certain harmful
      microorganisms. These peptides play an important role in protecting the chickweed
      plants from infection, and the pro-SmAMP2 gene was previously used to protect
      transgenic tobacco and Arabidopsis plants from phytopathogens. In this study, the
      pro-SmAMP2 gene under control of viral CaMV35S promoter or under control of its
      own pro-SmAMP2 promoter was transformed into cultivated potato plants of two
      cultivars, differing in the resistance to Alternaria: Yubiley Zhukova (resistant)
      and Skoroplodny (susceptible). With the help of quantitative real-time PCR, it
      was demonstrated that transgenic potato plants expressed the pro-SmAMP2 gene
      under control of both promoters at the level comparable to or exceeding the level
      of the potato actin gene. Assessment of the immune status of the transformants
      demonstrated that expression of antimicrobial peptide pro-SmAMP2 gene was able to
      increase the resistance to a complex of Alternaria sp. and Fusarium sp.
      phytopathogens only in potato plants of the Yubiley Zhukova cultivar. The
      possible role of the pro-SmAMP2 products in protecting potatoes from Alternaria
      sp. and Fusarium sp. is discussed.

PMID- 29369561
TI  - [Nuclear mtDNA pseudogenes as a source of new variants of the mtDNA cytochrome b
      haplotypes: A case study of Siberian rubythroat Luscinia calliope (Muscicapidae,
      Aves)].
AB  - Sequence polymorphism of the mitochondrial DNA cytochrome b gene fragment was
      analyzed in 21 specimens of subspecies Luscinia calliope calliope (Pallas, 1776)
      and two specimens of L. c. anadyrensis (Portenko, 1939). On sequence
      chromatograms, in 19 specimens of L. c. calliope, double peaks of heteroplasmy
      type in the taxon-specific positions were revealed. Moreover, two clone variants
      were identified. The first variant was the calliope mitochondrial cyt b gene and
      the second was the nuclear cyt b pseudogene, similar to the mitochondrial
      haplotype anadyrensis-camtschatkensis. In L. c. anadyrensis, four clone variants,
      represented by the mitochondrial calliope and anadyrensis-camtschatkensis cyt b
      genes and nuclear calliope and sachalinensis cyt b pseudogenes, were identified.
      Some nuclear cyt b pseudogenes were highly similar (98-99%) to the mitochondrial
      genes of the subspecies L. c. anadyrensis, L. c. camtschatkensis, and L. c.
      sachalinensis. In the same time, the majority of nuclear pseudogene sequences
      were characterized by a high level of polymorphism, caused by nonsynonymous
      substitutions (up to five substitutions per sequence), the presence of indels in
      some of the clones, and TAA and TGA stop codons. In our opinion, the
      mitochondrial haplotypes anadyrensis-camtschatkensis and sachalinensis occurred
      as a result of intergenomic homologous recombination. This finding provides a new
      insight into the colonization history of the northeastern part of the range by L.
      calliope, according to which populating the territory of Chukotka, Kamchatka, and
      Sakhalin took place at different times and along the independent pathways.

PMID- 29369562
TI  - [Characterization of the Russian beef cattle breed gene pools using inter simple
      sequence repeat DNA analysis (ISSR analysis)].
AB  - The gene pools of beef cattle breeds bred in Russia were characterized on the
      basis of inter simple sequence repeat DNA analysis (ISSR analysis). Samples of
      Aberdeen Angus, Kalmyk, and Kazakh Whitehead breeds from Russia, as well as of
      Hereford breed, hybrids of Kazakh Whitehead and Hereford breeds, and Kazakh
      Whitehead breed from the Republic of Kazakhstan, were examined. In the examined
      breeds, 27 AG-ISSR fragments were identified, 25 of which were polymorphic. The
      examined breeds were different both in the fragment profiles (the
      presence/absence of individual ISSR fragments) and in their frequencies. It was
      demonstrated that the hybrid animals lacked some ISSR fragments that were present
      with high frequencies in parental forms, suggesting considerable genome
      rearrangement in the hybrid animals (at the regions of microsatellite
      localization) in crossings of the individuals from different breeds. The level of
      genetic diversity in Russian beef breeds was consistent with the values typical
      of farmed populations (breeds). The genetic diversity parameters assessed by
      applying Nei's gene diversity index and the Shannon index varied from 0.0218 to
      0.0605 and from 0.0225 to 0.0819, respectively. The highest Shannon index value
      was detected in the Kalmyk breed (0.0837) and Kazakh Whitehead breed from Russia
      (0.0819), and the highest level of Nei's gene diversity index was found in the
      Kalmyk breed (0.0562) and in both populations of the Kazakh Whitehead breed
      (0.0509 and 0.0605). The high level of genetic similarity (according to Nei) was
      revealed between Russian beef cattle breeds and Hereford cattle: 0.839 (for the
      Kazakh Whitehead breed from Russia) and 0.769 (for the Kalmyk breed).

PMID- 29369563
TI  - Mathematical models in genetics.
AB  - In this study, we present some of the basic ideas of population genetics. The
      founders of population genetics are R.A. Fisher, S. Wright, and J. B.S. Haldane.
      They, not only developed almost all the basic theory associated with genetics,
      but they also initiated multiple experiments in support of their theories. One of
      the first significant insights, which are a result of the Hardy-Weinberg law, is
      Mendelian inheritance preserves genetic variation on which the natural selection
      acts. We will limit to simple models formulated in terms of differential
      equations. Some of those differential equations are nonlinear and thus emphasize
      issues such as the stability of the fixed points and time scales on which those
      equations operate. First, we consider the classic case when selection acts on
      diploid locus at which wu can get arbitrary number of alleles. Then, we consider
      summaries that include recombination and selection at multiple loci. Also, we
      discuss the evolution of quantitative traits. In this case, the theory is
      formulated in respect of directly measurable quantities. Special cases of this
      theory have been successfully used for many decades in plants and animals
      breeding.

PMID- 29369564
TI  - [Genetic determinants of resistance of hospital-associated strains of Klebsiella
      pneumoniae to beta-lactam antibiotics isolated in neonates].
AB  - According to the results of analysis of whole genome sequencing, the presence of
      genes having resistance to beta-lactam antibiotics in hospital-associated strains
      of Klebsiella pneumoniae was studied. The strains were isolated from neonatal
      intensive care units. The data obtained were compared with the results of
      antimicrobial susceptibility testing of isolated microorganisms. Among other
      strains resistant to cephalosporins, the dominance of genes of CTX-M-type
      extended-spectrum beta-lactamases was shown. It was revealed that one of eight
      strains phenotypically resistant and moderately resistant to carbapenems have the
      blaOXA-48 carbapenemase gene.

PMID- 29369565
TI  - [Mutational landscape of prostate tumors revealed by whole-exome sequencing].
AB  - The results of the whole-exome DNA sequencing of eight prostate adenocarcinoma
      patients are presented. DNA was isolated from the peripheral blood as well as
      healthy and tumor prostate tissue from each patient. Bioinformatics analysis was
      conducted and the most significant mutations in prostate cancer patients were
      revealed. The obtained data could be important for understanding of the molecular
      mechanisms of prostate cancer pathogenesis and facilitate development of new
      approaches for treatment of the disease.

PMID- 29369566
TI  - [Estimation of association of CNTN6 copy number variation with idiopathic
      intellectual disability].
AB  - Analysis of the prevalence of copy number variations of the CNTN6 gene, recently
      selected as a new candidate gene for intellectual disorders, was performed. Real
      time PCR did not detect any change in the number of CNTN6 gene copies in a group
      of 200 patients with impaired intellectual development. However, taking into
      account our data from the previous aCGH analysis and published data, the overall
      frequency of microdeletions and microduplications of CNTN6 was estimated as 1:
      265 (0.4%). The common phenotypic features of 40 patients with microdeletions and
      microduplications of CNTN6 appeared to be the autism spectrum disorders,
      developmental delay, intellectual disability, seizures, cognitive impairment,
      cardiological defects, and behavioral problems.

PMID- 29369581
TI  - [Induction of transcription through the scs insulator leads to abnormal
      development of Drosophila melanogaster].
AB  - A regulatory element named scs is one of the first insulators discovered in
      Drosophila, which was found on the boundary of the hsp70 domain. The 993-bp scs
      insulator contains two promoters at the ends and two polyadenylation signals
      located in the same orientation in the central part of the insulator. In the
      Drosophila transgenic lines, induction of a strong transcription through the scs
      insulator only in the direction that coincides with the direction of the two
      polyadenylation sites activity results in multiple phenotypic defects of the
      Drosophila development and embryonic lethality. A similar effect was not observed
      upon testing of other known Drosophila insulators.

PMID- 29369582
TI  - [Occurrence of islands in genomes of Sinorhizobium meliloti native isolates].
AB  - Genomes of 184 Sinorhizobium meliloti native isolates were studied to test the
      occurence of islands Sme21T, Sme19T, and Sme80S previously described in the model
      strain Rm1021. This analysis was conducted using PCR methodology involving
      specific primers. It was demonstrated that, in the examined geographically
      distinct populations of S. meliloti from the Northern Caucasus (NCG) and the Aral
      Sea region (PAG), the strains containing genomic islands were observed with
      similar frequency (0.55 and 0.57, respectively). Island Sme80S, denoted as an
      island of "environmental adaptivity," was identified predominantly (frequency of
      0.38) in genomes of strains which exhibited a lower level of salt tolerance and
      was isolated in PAG, a modern center of introgressive hybridization of alfalfa
      subjected to salinity. Island Sme21T designated as "ancestral" was observed in
      genomes of strains isolated in NCG, the primary center of host-plant
      biodiversity, 10-fold more often than in strains from PAG. An island Sme19T,
      which predominantly carries genes encoding transposases, was observed in genomes
      of strains in both populations with average frequency of 0.10. The analysis of
      linkage disequilibrium (LD) based on the assessment of probability for detection
      of different islands combinations in genomes revealed an independent inheritance
      of islands in salt-sensitive strains of various geographic origin. In contrast,
      the absence of this trend was noted in the majority of the examined combinations
      of salt-tolerant strains. It was concluded that the structure of chromosome in
      PAG strains which predominantly possessed a salt-sensitive phenotype was
      subjected to active recombinant processes, which could predetermine the intensity
      of microevolutionary processes in bacterial populations and facilitate an
      adaptation of bacteria in adverse environmental effect.

PMID- 29369583
TI  - [Genetic polymorphism of Tulipa gesneriana L. evaluated on the basis of the ISSR
      marking data].
AB  - Using the method of ISSR analysis, the genetic diversity of 18 natural
      populations of Tulipa gesneriana L. from the north of the Lower Volga region was
      examined. The ten ISSR primers used in the study provided identification of 102
      PCR fragments, of which 50 were polymorphic (49.0%). According to the proportion
      of polymorphic markers, two population groups were distinguished: (1) the
      populations in which the proportion of polymorphic markers ranged from 0.35 to
      0.41; (2) the populations in which the proportion of polymorphic markers ranged
      from 0.64 to 0.85. UPGMA clustering analysis provided subdivision of the sample
      into two large clusters. The unrooted tree constructed using the Neighbor Joining
      algorithm had similar topology. The first cluster included slightly variable
      populations and the second cluster included highly variable populations. The
      AMOVA analysis showed statistically significant differences (F CT = 0.430; p =
      0.000) between the two groups. Local populations are considerably genetically
      differentiated from each other (F ST = 0.632) and have almost no links via modern
      gene flow, as evidenced by the results of the Mantel test (r =-0.118; p = 0.819).
      It is suggested that the degree of genetic similarities and differences between
      the populations depends on the time and the species dispersal patterns on these
      territories.

PMID- 29369584
TI  - [Allelic diversity of hordein-coding loci Hrd A and Hrd B in cultivated (Hordeum
      vulgare L.) and wild (H. spontaneum C. Koch) barley from Iran (as a part of the
      Fertile Crescent)].
AB  - Polymorphism of hordeins encoded by the Hrd A and Hrd B loci was studied using
      starch gel electrophoresis in 63 landraces of cultivated barley (H. vulgare) and
      43 accessions of wild barley (H. spontaneum) from Iran. We identified 35 and 32
      Hrd A alleles of H. vulgare and H. spontaneum. The number of Hrd B alleles in
      these species was 55 and 48, respectively. The frequencies of alleles in the Hrd
      A and Hrd B loci in cultivated barley varied within the range of 0.0016-0.2816
      (Hrd A) and 0.0016-0.1221 (Hrd B). The allelic frequencies in wild barley ranged
      within 0.0077-0.2170 and 0.0077-0.0815, respectively. Iranian accessions of H.
      spontaneum and H. vulgare shared some alleles; the number of common alleles was
      seven for the Hrd A locus and five for the Hrd B locus. These alleles were
      detected mainly in accessions of wild barley heterozygous or heterogenic for
      hordein-coding loci. We concluded that the regions close to Zagros mountain range
      cannot be considered as a barley domestication center. At the same time, Iranian
      H. spontaneum could have donated some hordein-coding loci to H. vulgare as a
      result of introgressions occurring because of spontaneous hybridization over the
      course of the spread of cultivated barley.

PMID- 29369585
TI  - [The recovering of breeding achievements of Populus * leningradensis bogd. and
      Populus * newensis bogd. Based on microsatellite analysis].
AB  - The genotyping of 75 trees from poplar plantations in St. Petersburg and
      Leningrad oblast was conducted with microsatellite markers to identify the elite
      clonal varieties developed by P.L. Bogdanov in the period of 1938-1965. The
      information about the varieties was lost. The authentic herbarium specimens of
      poplar clonal varieties preserved at the St. Petersburg State Forest Technical
      University were used as reference genotypes. According to the results of DNA
      fingerprinting, we identified the clonal plantations of Populus * newesis Bogd.
      and Populus * leningradensis Bogd. from the Kartashevskii forest district and the
      arboretum of the St. Petersburg State Forest Technical University. The identified
      elite poplar hybrids have a higher frost resistant and a higher growth rate. They
      are recommended for plantation cultivation in the northwest of Russia.

PMID- 29369586
TI  - Emergency department management of patients with thermal burns.
AB  - Thermal burn injuries are a significant cause of morbidity and mortality
      worldwide. In addition to treatment of the burns, emergency clinicians must
      assess for inhalation injury, exposure to toxic gases, and related traumatic
      injuries. Priorities for emergency resuscitation include stabilization of airway
      and breathing, intravenous fluid administration, pain control, and local wound
      care. Special populations, including children and pregnant women, require
      additional treatment considerations. Referral to specialized burn care for select
      patients is necessary to improve long-term outcomes. This article reviews thermal
      burn classification and evidence-based treatment strategies.

PMID- 29369587
TI  - [New single nucleotide polymorphisms of androgen receptor gene (AR) in the
      Russian breed of Dzhalginsky Merino sheep].
AB  - This paper investigates the structure of androgen receptor gene (AR) in the
      Russian breed of Dzhalginsky Merino sheep. Polymorphisms of the gene were
      detected using NimbleGen sequencing technology (Roche, United States). Eight
      single nucleotide polymorphisms (SNPs) and two insertions were detected. Five of
      these SNPs (c.335T>G, c.339G>A, c.342T>C, c.2491-327T>A, and c.2491-325A>T) and
      both insertions were identified for the first time. Three SNPs and the insertions
      are located in the coding part of exon. Insertion c.336_337 is found in most of
      the animals of this breed and can be used as a genomic marker of the breed.
      Animals with mutant variant of SNP c.1496+15T>C have significantly lower live
      weight and body size compared with the wild type genotype. This SNP can be used
      as a genetic marker of meat production in marker-assisted selection.

PMID- 29369588
TI  - [Seven genes of mitochondrial genome enabling differentiation of honeybee
      subspecies Apis mellifera].
AB  - On the basis of comparative sequence analysis of 12 honeybee mitochondrial genes,
      seven genes enabling us to differentiate honeybees subspecies of the A, M, C, O
      evolutionary lineages were found. Applying comparative sequence analysis of ND2
      gene mtDNA as an example on a statistically valid sample size, we showed a high
      level of differentiating ability of this gene and assumed that each of these
      seven genes probably can be used for differentiation of the subspecies within
      four evolutionary lineages.

PMID- 29369589
TI  - [Alu insertion-deletion polymorphism of COL13A1 and LAMA2 genes: The analysis of
      association with longevity].
AB  - The distribution of allele and genotype frequencies of Alu(I/D) polymorphic sites
      in the COL13A1 and LAMA2 genes coding extracellular matrix protein subunits was
      characterized in an ethnically homogeneous group (Tatars from the Republic of
      Bashkortostan, Russia). It was established that the frequency of individuals with
      the COL13A1*D/*D genotype was higher in the senile age period. The LAMA2*I/*D
      genotype was predisposing to longevity among women. According to the observed
      results, the frequency of the LAMA2*I/*D genotype was increased in senile
      individuals older than 90 years. The observed associations can be explained on
      the basis of the contemporary view by the importance of Alu elements in gene
      expression regulation at transcriptional and post-transcriptional levels, the
      involvement of collagen and laminin in maintaining the structure and function of
      the extracellular matrix, and the relationship between the extracellular matrix
      state, pathological changes and aging.

PMID- 29369590
TI  - [Population frequency and age of mutation G5741->A in gene NBAS which is a cause
      of SOPH syndrome in Sakha (Yakutia) Republic].
AB  - SOPH syndrome (Short stature with Optic nerve atrophy and Pelger-Huet anomaly
      syndrome, OMIM#614800) is an autosomal recessive hereditary disease characterized
      by the following main clinical symptoms: postnatal hypoplasia, proportionately
      short stature, facial dysmorphism, micromelia of feet and hands, limp and loose
      skin, optic nerve atrophy, and Pelger-Huet anomaly of neutrophils. For the first
      time, this disease was described in Yakuts. The molecular-genetic study showed
      that its cause in Yakuts is mutation G5741->A in gene NBAS. On the basis of
      disequilibrium analysis for linkage of ten microsatellite markers flanking the
      NBAS gene with the disease, the haplotype of the founder chromosome was
      determined. The age of the mutation in Yakutia was estimated to be about 804 +/-
      140 years. The frequency of heterozygous carriers of mutation G5741->A (R1914H)
      in gene NBAS was found, which averaged 13 per 1000 healthy Yakuts.

PMID- 29369591
TI  - Acute gastroenteritis: evidence-based management of pediatric patients.
AB  - Although most cases of acute gastroenteritis require minimal medical
      intervention, severe dehydration and hypoglycemia may develop in cases of
      prolonged vomiting and diarrhea. The mainstay of treatment for mild-to-moderately
      dehydrated patients with acute gastroenteritis should be oral rehydration
      solution. Antiemetics allow for improved tolerance of oral rehydration solution,
      and, when used appropriately, can decrease the need for intravenous fluids and
      hospitalization. This issue reviews the common etiologies of acute
      gastroenteritis, discusses more-severe conditions that should be considered in
      the differential diagnosis, and provides evidence-based recommendations for
      management of acute gastroenteritis in patients with mild-to-moderate
      dehydration, severe dehydration, and hypoglycemia.

PMID- 29369592
TI  - [Functional linear models for region-based association analysis].
AB  - Regional association analysis is one of the most powerful tools for gene mapping
      because instead analysis of individual variants it simultaneously considers all
      variants in the region. Recent development of the models for regional association
      analysis involves functional data analysis approach. In the framework of this
      approach, genotypes of variants within region as well as their effects are
      described by continuous functions. Such approach allows us to use information
      about both linkage and linkage disequilibrium and reduce the influence of noise
      and/or observation errors. Here we define a functional linear mixed model to test
      association on independent and structured samples. We demonstrate how to test
      fixed and random effects of a set of genetic variants in the region on
      quantitative trait. Estimation of statistical properties of new methods shows
      that type I errors are in accordance with declared values and power is high
      especially for models with fixed effects of genotypes. We suppose that new
      functional regression linear models facilitate identification of rare genetic
      variants controlling complex human and animal traits. New methods are implemented
      in computer software FREGAT which is available for free download at
      http://mga.bionet.nsc.ru/soft/FREGAT/.

PMID- 29369593
TI  - [Escherichia coli ydiO and ydiQRST genes encode components of acyl-CoA
      dehydrogenase complex of anaerobic fatty acid beta-oxidation pathway].
AB  - Escherichia coli open reading frames ydiO and ydiQRST were identified as genes
      encoding components of the acyl-CoA dehydrogenase complex of anaerobic fatty acid
      beta-oxidation. Individual or concomitant inactivation of fadE gene, encoding
      known aerobic acyl-CoA dehydrogenase, and ydiO and/or ydiQRST genes did not
      affect cellular growth on glucose as a sole carbon source. Aerobic growth on
      sodium oleate was observed only for the cells with intact fadE gene. With an
      alternative electron acceptor, the cells possessing intact fadE gene demonstrated
      anaerobic growth on sodium oleate irrespective of the presence or absence of ydiO
      and ydiQRST genes. For the fadE-deficient mutants, anaerobic growth on sodium
      oleate was observed only for cells with intact ydiO and ydiQRST genes, while the
      fadE/ydiO and fadE/ydiQRST mutants failed to grow under the similar conditions.

PMID- 29369595
TI  - Insight in schizophrenia - a double-edged sword?
AB  - Lack of insight is defined as a loss of ability to distinguish that one's unusual
      and unreal experiences should be the symptoms of the psychiatric disorder
      requiring treatment. Lack of insight may be considered as a core symptom of
      schizophrenia. The concept of insight has been regarded for a long time as
      necessary for treatment, which improves adherence and makes a better prognosis.
      Increased insight in schizophrenia has been associated not only with benefits,
      but also bring trouble in the form of self-stigma, low self-esteem, reduced
      patient's hope, diminished quality of life, and increased suicidality. Therefore,
      insight should be managed with sensitive monitoring of the risk factors, and be
      gradual, carefully supported by the encouragement of hope and confidence to
      managing everyday life.

PMID- 29369596
TI  - Melatonin with adenosine solubilized in water and stabilized with glycine for
      oncological treatment - technical preparation, effectivity and clinical findings.
AB  - Melatonin has shown the potential to inhibit growth of different tumors, both in
      vitro and in vivo. There is clear evidence that the administration of melatonin
      alone or in combination with chemo and radiotherapy in cancer patients with
      advanced solid tumors has been associated with improved outcomes of tumor
      regression and survival. Moreover, chemotherapy has been shown to be better
      tolerated in patients treated with melatonin. However, there are different ways
      of preparation and administration of melatonin to the patient. This review
      article aims to offer the insight into the preparation, biological features and
      clinical findings in its use in cancer patients. Melatonin (MLT) can only be
      solubilized in water at 40-45  degrees C; at other temperatures it can only be
      solubilized in alcohol. It is absorbed in the human body complexed with adenosine
      by a hydrogen bond. It acts on two common denominators: proliferation and
      differentiation; in addition to anticancer homeostasis, MLT has a documented
      antidegenerative and immunomodulatory role. It also plays an important role in
      limiting oxidative stress, affecting blood and bone marrow constituent ratio,
      leukocyte formula regulation, hemoglobin synthesis, platelet genesis, aggregation
      and in erythrocyte resistance. Despite of all these important roles, most well
      known features are probably the least important ones, such as sleep and
      wakefulness regulation and its effect on jet lag. In the preparation formulated
      by Prof. Di Bella, melatonin with adenosine at a ratio of 1:4, stabilized with
      30% of glycine (MLT-DBM), has been used since 1994 in many patients with various
      indications and positive therapeutic responses and a total absence of toxicity.
      This method can be a good alternative to commercially produced preparations, as
      it was scientifically proved and published worldwide at conferences and in
      various medical journals.

PMID- 29369597
TI  - How long does the pharmacokinetic interaction between carbamazepine and
      quetiapine last after carbamazepine withdrawal?
AB  - OBJECTIVES: Carbamazepine and quetiapine are drugs that are used as mood
      stabilizers in the treatment of bipolar disorders. A series of studies has shown
      that concurrent use of carbamazepine decreases quetiapine serum level due to
      induction of CYP3A enzymes by carbamazepine. METHODS: In a 30-year-old bipolar
      patient with mania treated with quetiapine 1200 mg and carbamazepine 900 mg per
      day, we measured quetiapine serum level before and after carbamazepine
      withdrawal. RESULTS: No serum quetiapine was detected during concurrent use of
      carbamazepine and was lower than the therapeutic range almost 2 weeks after
      carbamazepine withdrawal. The patient suffered from sedation when her serum level
      of quetiapine was 181 ng/ml and because she was quiet we started slowly to
      decrease to a quetiapine dose of 600 mg. Her serum level (45 ng/ml) was again
      below therapeutic levels after 3 weeks of carbamazepine withdrawal. CONCLUSION:
      We hypothesize that induction of CYP3A lasts even after carbamazepine withdrawal.
      Our hypothesis was confirmed during the next treatment of mania. The patient had
      been off carbamazepine for 1 year and her serum level was four times higher (210
      ng/ml) on 600 mg of quetiapine than 3 weeks after carbamazepine withdrawal. The
      influence of carbamazepine on CYP3A enzymes lasted at least 3 weeks after
      carbamazepine withdrawal which is in accordance with CYP3A de-induction lasting 3
      weeks. This could be important information for psychiatrists to know that in some
      patients it is better to use a minimum washout period of 3 weeks for
      carbamazepine before new treatment with quetiapine.

PMID- 29369598
TI  - A case of hereditary thrombophilia in a Chinese Han patient with both
      antithrombin deficiency and Factor V Leiden: A case report and literature review.
AB  - Hereditary thrombophilia is a blood coagulation disorder that increases the risk
      of venous thromboembolism, due to several genetic risk factors. Factor V
      Leiden(FVL) is the most common contributing factor to thrombophilia in the
      Caucasian population but very rare in Asian population and concurrent occurrence
      of antithrombin(AT) deficiency and FVL in Chinese Han population is even more
      rare. We report the case of a 22-year-old female who experienced recurrent
      intracranial venous thromboses, furthermore, color Doppler ultrasound showed
      multiple extracranial thromboses. Thrombophilia was suspected and screening tests
      indicated decreased AT activity and activated protein C sensitivity ratio, then
      further sequencing analysis identified missense mutations in SERPINC1 and F5. The
      patient's condition slightly improved after treatment with low molecular heparin
      during hospitalization followed by oral warfarin after discharge. The present
      report highlights a very rare case of thrombophilia with concurrent occurrence of
      AT deficiency and FVL in a Chinese Han patient, and our findings suggest that
      genetic testing is a reliable approach for identifying different risk factors.

PMID- 29369599
TI  - Application of physiotherapy in persons at risk of metabolic syndrome
      development.
AB  - Problems the locomotor activity and nutritional provisions in the treatment of
      obesity or metabolic syndrome are currently widely discussed. Based on prevailing
      experience, the attention in the field of locomotor and fitness activities is
      rather general, i.e. is mainly focused on the development of the general body
      fitness and reduction fitness programmes. However, no long-term effects of the
      locomotor therapy can be expected without appropriate and particularly targeted
      physiotherapy with a thorough kinesiological examination. Case report described
      here monitored the course of a three-month physiotherapeutic intervention in
      person having enhanced values of the waist circumference in accordance with
      criteria of the metabolic syndrome, who previously attended a programme of diet
      provisions without meeting with success. In this case, positive results of
      reductions in the waist circumference and further dimensions were achieved in
      spite of the fact that in the course of the physiotherapy no arrangements of
      nutritional habits have been introduced.

PMID- 29369600
TI  - Postoperative hypoparathyroidism in patients after total thyroidectomy -
      retrospective analysis.
AB  - OBJECTIVES: Hypoparathyroidism is the most frequent complication of
      thyroidectomy. The incidence rates of temporary and permanent postoperative
      hypoparathyroidism vary from 7 to more than 60% and from 0 to 9%, respectively.
      DESIGN: The aim of the study has been to evaluate the incidence of
      hypoparathyroidism and clinical manifestations of hypocalcaemia after total
      thyroidectomy, as well as assess factors that affect the frequency of the
      symptomatic hypocalcaemia, and benefits resulting from the measurement of
      parathyroid hormone (PTH) concentration on the first day after thyroidectomy.
      SETTING: The studied group consisted of 330 patients after total thyroidectomy,
      while the control group consisted of 86 patients who underwent total resection of
      one lobe only or subtotal thyroidectomy. RESULTS: Based on the measurements of
      serum PTH concentration on the first day after total thyroidectomy, postoperative
      hypoparathyroidism was diagnosed in 48% of patients. After total thyroidectomy,
      the frequency of clinical symptoms of hypocalcaemia was twice less than the
      incidence of hypoparathyroidism confirmed by biochemical testing. Total
      thyroidectomy occurred to be an independent factor of the increased risk of
      postoperative hypoparathyroidism. This risk was even higher in the cases widened
      by lymphadenectomy, and among patients with Graves' disease. In the group of
      patients with decreased serum PTH concentration the occurrence of clinical
      symptoms of hypocalcaemia significantly depended on serum PTH concentration -
      patients with lower PTH levels reported paresthesias more frequently.
      CONCLUSIONS: Serum PTH levels below 5 pg/ml seems to be a good prognostic factor
      of the occurrence of hypocalcaemia symptoms. The information about low PTH
      concentration allows to start the pharmacotherapy faster and avoid clinical
      manifestation of hypocalcaemia.

PMID- 29369601
TI  - Study of locomotion, rearing and grooming activity after single and/or
      concomitant lesions of central and peripheral nervous system in rats.
AB  - OBJECTIVE: Locomotion, rearing and grooming represent different forms of
      behaviour and motor activity in rats. In this study, changes in these activities
      were analysed in relation to impaired function of the nervous system by single
      and/or concomitant lesions representing an experimental model of the dual
      diagnosis. METHODS: 32 rats were divided into 4 groups of 8 rats: intact rats,
      rats with single lesion of peripheral nervous system (PNS) - Marcaine neuropathy,
      rats with single CNS lesion - cellular brain edema induced by water intoxication,
      and the concomitant lesions (combination of CNS and PNS lesion in one rat). Water
      intoxication was performed in a standard way by fractionated hyperhydration. The
      average time spent by locomotion, rearing and grooming was registered and
      analyzed using an open field test. RESULTS: All activities of the rats after
      water intoxication became inhibited due to the generally suppressive effect of
      brain edema. Lesion of PNS reduced activity in locomotion only, because for
      rearing and grooming activities, the function of the forelimb is not dominant.
      Combination of lesions (dual diagnosis) reduced locomotion and rearing activity
      more than single lesions, and enhances the stressogenic effect, which was
      manifested by a long periods of grooming. CONCLUSION: Results of our study
      confirmed the physiological and pathophysiological differences in the movement
      stereotype between locomotion, rearing and grooming caused by the characteristics
      and algorithms of the movements, which are inborn to rats - the dominant role of
      the forelimbs in locomotion, the dominant exploratory activity in rearing, and
      the precise syntactic movement pattern in grooming.

PMID- 29369602
TI  - Evaluation of the amoxicillin concentrations in amniotic fluid, placenta,
      umbilical cord blood and maternal serum two hours after oral administration.
AB  - OBJECTIVES: Amoxicillin is a broad-spectrum beta-lactam antibiotic. Due to its
      low toxicity, it is commonly used in obstetrics. The objective of this study was
      to assess amoxicillin concentrations in amniotic fluid, umbilical blood, placenta
      and maternal serum two hours following oral administration among pregnant women
      at term and to assess obstetric and non-obstetric factors that might affect
      amoxicillin's penetration of these tissues. MATERIALS AND METHODS: A total of 30
      full-term pregnant women who qualified for elective Caesarean delivery were
      included in the study. Amoxicillin at a dose of 500 mg was administered prior to
      surgery. Amoxicillin levels were determined by diffusion microbial assay.
      RESULTS: The maternal serum, placental, umbilical blood and amniotic fluid levels
      of amoxicillin two hours after oral administration were 2.18+/-1.30 ug/g, 1.00+/
      0.71 ug/g, 1.00+/-0.73 ug/g, and 0.67+/-0.59 ug/g, respectively (Table 2).
      Maternal serum levels of amoxicillin were significantly higher compared to other
      tissues (p<0.05). CONCLUSION: If the target tissues for the use of antibiotic
      drugs in pregnant patients are the fetus and/or the placenta, the drug should be
      administered in a higher-than-standard dose than that used to treat infections in
      non-pregnant patients. Considering that there is a maximum absorbable dose
      following oral administration, intravenous administration should be considered to
      prevent failure of antibiotic treatment. A higher dose of amoxicillin should be
      considered in obese mothers.

PMID- 29369604
TI  - Calculated decisions: Parkland formula for burns

PMID- 29369603
TI  - Circadian blood pressure profiles and ambulatory arterial stiffness index in
      children and adolescents with congenital adrenal hyperplasia due to 21
      hydroxylase deficiency in relation to their genotypes.
AB  - OBJECTIVE: Lifelong steroid therapy and exposure to adrenal androgen excess in 21
      hydroxylase deficient (21-OHD) congenital adrenal hyperplasia (CAH) children and
      adolescents may modify circadian blood pressure profile and result in vascular
      complications. The objective of the study was to evaluate vascular abnormalities
      in 21-OHD children and adolescents in relation to their genotypes. DESIGN: A
      cross-sectional study conducted at a tertiary referral center. PATIENTS: Seventy
      patients with 21-OHD CAH (27 boys), aged from 3 to 17.9 years: 9 with nonclassic
      CAH, 61 with classic CAH: 10 with simple virilising (SV) and 51 with salt wasting
      CAH (13-Del/Del, 8-Del/I2G, 7-I2G/I2G and 23-other genotypes). MAIN OUTCOMES
      MEASURES: The assessment of systolic and diastolic BP (SBP, DBP) loads, night
      dip% and arterial ambulatory stiffness index (AASI) in 21-OHD CAH patients.

PMID- 29369605
TI  - [The search for new candidate genes involved in ovarian cancer pathogenesis by
      exome sequencing].
AB  - Ovarian cancer is one of the most insidious of tumors among gynecological cancers
      in the world. BRCA1 and BRCA2 mutations are associated with high risk of ovarian
      cancer; however, they are causative only in a fraction of cases. The search for
      new genes would expand our understanding of the mechanisms underlying malignant
      ovarian tumors and could help to develop new methods of early diagnosis and
      treatment of the disease. The present study involved exome sequencing of eight
      DNA samples extracted from the blood of ovarian cancer patients. As a result of
      the study, 53057 modifications in one sample were identified on average. Of them,
      222 nucleotide sequence modifications in DNA located in exons and splice sites of
      203 genes were selected. On the basis of the function of these genes in the cell
      and their involvement in carcinogenesis, 40 novel candidate genes were selected.
      These genes are involved in cell cycle control, DNA repair, apoptosis, regulation
      of cell invasion, proliferation and growth, transcription, and also immune
      response and might be involved in development of ovarian cancer.

PMID- 29369606
TI  - [Chromosomal localization of aromatic alcohol dehydrogenase fast-migrating
      isoenzyme Aadh1F (CAD1-F) gene in Triticum aestivum L. bread wheat].
AB  - Differences in isoenzyme pattern of aromatic alcohol dehydrogenase, NADP-AADH or
      CAD, were found in the Triticum aestivum L. winter bread wheat cultivars by the
      method of electrophoresis in the starch gel. A standard three-component spectrum
      is present in the cv. Zitnica (former Yugoslavia); additional fact-migrating
      isoenzymes appear in the cv. Novosibirskaya 9 (Institute of Cytology and
      Genetics, Siberian Branch, Russian Academy of Sciences, Russia). The presence of
      fast-migrating CAD isoenzymes is designated as FF phenotype; their absence, as 00
      phenotype. Hybridological analysis was carried out; the excess of "null"
      genotypes was found in F2 progenies. Hybridization with nulli-tetrasomic lines of
      the chromosomes of the fifth homeologous group was conducted for the gene
      localization. The segregation analysis demonstrated the most probable
      localization of the CAD1-F gene in the chromosome 5A. The plants with FF and 00
      genotypes differed in a number of chemical and anatomical traits, as well as in
      grain productivity. The results obtained are discussed in connection with the
      function of this enzyme in the wheat plant tissues.

PMID- 29369608
TI  - Nanostructured Electrochemical Biosensors for Label-Free Detection of Water- and
      Food-Borne Pathogens.
AB  - The emergence of nanostructured materials has opened new horizons in the
      development of next generation biosensors. Being able to control the design of
      the electrode interface at the nanoscale combined with the intrinsic
      characteristics of the nanomaterials engenders novel biosensing platforms with
      improved capabilities. The purpose of this review is to provide a comprehensive
      and critical overview of the latest trends in emerging nanostructured
      electrochemical biosensors. A detailed description and discussion of recent
      approaches to construct label-free electrochemical nanostructured electrodes is
      given with special focus on pathogen detection for environmental monitoring and
      food safety. This includes the use of nanoscale materials such as nanotubes,
      nanowires, nanoparticles, and nanosheets as well as porous nanostructured
      materials including nanoporous anodic alumina, mesoporous silica, porous silicon,
      and polystyrene nanochannels. These platforms may pave the way toward the
      development of point-of-care portable electronic devices for applications ranging
      from environmental analysis to biomedical diagnostics.

PMID- 29369609
TI  - Silk Fibroin Separators: A Step Toward Lithium-Ion Batteries with Enhanced
      Sustainability.
AB  - Battery separators based on silk fibroin (SF) have been prepared aiming at
      improving the environmental issues of lithium-ion batteries. SF materials with
      three different morphologies were produced: membrane films (SF-F), sponges
      prepared by lyophilization (SF-L), and electrospun membranes (SF-E). The latter
      materials presented a suitable porous three-dimensional microstructure and were
      soaked with a 1 M LiPF6 electrolyte. The ionic conductivities for SF-L and SF-E
      were 1.00 and 0.32 mS cm-1 at 20  degrees C, respectively. A correlation between
      the fraction of beta-sheet conformations and the ionic conductivity was observed.
      The electrochemical performance of the SF-based materials was evaluated by
      incorporating them in cathodic half-cells with C-LiFePO4. The discharge
      capacities of SF-L and SF-E were 126 and 108 mA h g-1, respectively, at the C/2
      rate and 99 and 54 mA h g-1, respectively, at the 2C-rate. Furthermore, the
      capacity retention and capacity fade of the SF-L membrane after 50 cycles at the
      2C-rate were 72 and 5%, respectively. These electrochemical results show that a
      high percentage of beta-sheet conformations were of prime importance to guarantee
      excellent cycling performance. This work demonstrates that SF-based membranes are
      appropriate separators for the production of environmentally friendlier lithium
      ion batteries.

PMID- 29369610
TI  - Conductive Nature of Grain Boundaries in Nanocrystalline Stabilized Bi2O3 Thin
      Film Electrolyte.
AB  - Stabilized Bi2O3 has gained a considerable amount of attention as a solid
      electrolyte material for low-temperature solid oxide fuel cells due to its
      superior oxygen-ion conductivity at the temperature of relevance (<=500  degrees
      C). Despite many research efforts to measure the transport properties of
      stabilized Bi2O3, the effects of grain boundaries on the electrical conductivity
      have rarely been reported and their results are even controversial. Here, we
      attempt quantitatively to assess the grain boundary contribution out of the total
      ionic conductivity at elevated temperatures (350-500  degrees C) by fabricating
      epitaxial and nano-polycrystalline thin films of yttrium-stabilized Bi2O3.
      Surprisingly, both epitaxial and polycrystalline films show nearly identical
      levels of ionic conductivity, as measured by alternating current impedance
      spectroscopy and this is the case despite the fact that the polyfilm possesses
      nanosized columnar grains and thus an extremely high density of the grain
      boundaries. The highly conductive nature of grain boundaries in stabilized Bi2O3
      is discussed in terms of the clean and chemically uniform grain boundary without
      segregates, and the implications for device application are suggested.

PMID- 29369611
TI  - Local Plasmon Engineering in Doped Graphene.
AB  - Single-atom B or N substitutional doping in single-layer suspended graphene,
      realized by low-energy ion implantation, is shown to induce a dampening or
      enhancement of the characteristic interband pi plasmon of graphene through a high
      resolution electron energy loss spectroscopy study using scanning transmission
      electron microscopy. A relative 16% decrease or 20% increase in the pi plasmon
      quality factor is attributed to the presence of a single substitutional B or N
      atom dopant, respectively. This modification is in both cases shown to be
      relatively localized, with data suggesting the plasmonic response tailoring can
      no longer be detected within experimental uncertainties beyond a distance of
      approximately 1 nm from the dopant. Ab initio calculations confirm the trends
      observed experimentally. Our results directly confirm the possibility of
      tailoring the plasmonic properties of graphene in the ultraviolet waveband at the
      atomic scale, a crucial step in the quest for utilizing graphene's properties
      toward the development of plasmonic and optoelectronic devices operating at
      ultraviolet frequencies.

PMID- 29369612
TI  - Discovery of Small Molecule Therapeutics for Treatment of Chronic HBV Infection.
AB  - The chronic infection of hepatitis B virus (HBV) inflicts 250 million people
      worldwide representing a major public health threat. A significant subpopulation
      of patients eventually develop cirrhosis and hepatocellular carcinoma (HCC).
      Unfortunately, none of the current standard therapies for chronic hepatitis B
      (CHB) result in a satisfactory clinical cure rate. Driven by a highly unmet
      medical need, multiple pharmaceutical companies and research institutions have
      been engaged in drug discovery and development to improve the CHB functional cure
      rate, defined by sustainable viral suppression and HBsAg clearance after a finite
      treatment. This Review summarizes the recent advances in the discovery and
      development of novel anti-HBV small molecules. It is believed that an improved
      CHB functional cure rate may be accomplished via the combination of molecules
      with distinct MoAs. Thus, certain molecules may evolve into key components of a
      suitable combination therapy leading to superior outcome of clinical efficacy in
      the future.

PMID- 29369613
TI  - Direct Imprinting of Scalable, High-Performance Woodpile Electrodes for Three
      Dimensional Lithium-Ion Nanobatteries.
AB  - The trend of device downscaling drives a corresponding need for power source
      miniaturization. Though numerous microfabrication methods lead to successful
      creation of submillimeter-scale electrodes, scalable approaches that provide cost
      effective nanoscale resolution for energy storage devices such as on-chip
      batteries remain elusive. Here, we report nanoimprint lithography (NIL) as a
      direct patterning technique to fabricate high-performance TiO2 nanoelectrode
      arrays for lithium-ion batteries (LIBs) over relatively large areas. The critical
      electrode dimension is below 200 nm, which enables the structure to possess
      favorable rate capability even under discharging current densities as high as
      5000 mA g-1. In addition, by sequential imprinting, electrodes with three
      dimensional (3D) woodpile architecture were readily made in a "stack-up" manner.
      The height of architecture can be easily controlled by the number of stacked
      layers while maintaining nearly constant surface-to-volume ratios. The result is
      a proportional increase of areal capacity with the number of layers. The
      structure-processing combination leads to efficient use of the material, and the
      resultant specific capacity (250.9 mAh g-1) is among the highest reported. This
      work provides a simple yet effective strategy to fabricate nanobatteries and can
      be potentially extended to other electroactive materials.

PMID- 29369614
TI  - Polymer-Brush-Templated Three-Dimensional Molybdenum Sulfide Catalyst for
      Hydrogen Evolution.
AB  - Earth-abundant hydrogen evolution catalysts are essential for high-efficiency
      solar-driven water splitting. Although a significant amount of studies have been
      dedicated to the development of new catalytic materials, the microscopic assembly
      of these materials has not been widely investigated. Here, we describe an
      approach to control the three-dimensional (3D) assembly of amorphous molybdenum
      sulfide using polymer brushes as a template. To this end, poly(dimethylaminoethyl
      methacrylate) brushes were grown from highly oriented pyrolytic graphite. These
      cationic polymer films bind anionic MoS42- through an anion-exchange reaction. In
      a final oxidation step, the polymer-bound MoS42- is converted into the amorphous
      MoSx catalyst. The flexibility of the assembly design allowed systematic
      optimization of the 3D catalyst. The best system exhibited turnover frequencies
      up to 1.3 and 4.9 s-1 at overpotentials of 200 and 250 mV, respectively. This
      turnover frequency stands out among various molybdenum sulfide catalysts. The
      work demonstrates a novel strategy to control the assembly of hydrogen evolution
      reaction catalysts.

PMID- 29369615
TI  - Nanoparticulate Dielectric Overlayer for Enhanced Electric Fields in a Capacitive
      Deionization Device.
AB  - The magnitude and distribution of the electric field between two conducting
      electrodes of a capacitive deionization (CDI) device plays an important role in
      governing the desalting capacity. A dielectric coating on these electrodes can
      polarize under an applied potential to modulate the net electric field and hence
      the salt adsorption capacity of the device. Using finite element models, we show
      the extent and nature of electric field modulation, associated with changes in
      the size, thickness, and permittivity of commonly used nanostructured dielectric
      coatings such as zinc oxide (ZnO) and titanium dioxide (TiO2). Experimental data
      pertaining to the simulation are obtained by coating activated carbon cloth (ACC)
      with nanoparticles of ZnO and TiO2 and using them as electrodes in a CDI device.
      The dielectric-coated electrodes displayed faster desalting kinetics of 1.7 and
      1.55 mg g-1 min-1 and higher unsaturated specific salt adsorption capacities of
      5.72 and 5.3 mg g-1 for ZnO and TiO2, respectively. In contrast, uncoated ACC had
      a salt adsorption rate and capacity of 1.05 mg g-1 min-1 and 3.95 mg g-1,
      respectively. The desalting data is analyzed with respect to the electrical
      parameters of the electrodes extracted from cyclic voltammetry and impedance
      measurements. Additionally, the obtained results are correlated with the
      simulation data to ascertain the governing principles for the changes observed
      and advances that can be achieved through dielectric-based electrode
      modifications for enhancing the CDI device performance.

PMID- 29369616
TI  - Interfacial Cation-Defect Charge Dipoles in Stacked TiO2/Al2O3 Gate Dielectrics.
AB  - Layered atomic-layer-deposited and forming-gas-annealed TiO2/Al2O3 dielectric
      stacks, with the Al2O3 layer interposed between the TiO2 and a p-type germanium
      substrate, are found to exhibit a significant interface charge dipole that causes
      a ~-0.2 V shift of the flat-band voltage and suppresses the leakage current
      density for gate injection of electrons. These effects can be eliminated by the
      formation of a trilayer dielectric stack, consistent with the cancellation of one
      TiO2/Al2O3 interface dipole by the addition of another dipole of opposite sign.
      Density functional theory calculations indicate that the observed interface
      dependent properties of TiO2/Al2O3 dielectric stacks are consistent in sign and
      magnitude with the predicted behavior of AlTi and TiAl point-defect dipoles
      produced by local intermixing of the Al2O3/TiO2 layers across the interface.
      Evidence for such intermixing is found in both electrical and physical
      characterization of the gate stacks.

PMID- 29369617
TI  - Direct Observation of Semiconductor-Metal Phase Transition in Bilayer Tungsten
      Diselenide Induced by Potassium Surface Functionalization.
AB  - Structures determine properties of materials, and controllable phase transitions
      are, therefore, highly desirable for exploring exotic physics and fabricating
      devices. We report a direct observation of a controllable semiconductor-metal
      phase transition in bilayer tungsten diselenide (WSe2) with potassium (K) surface
      functionalization. Through the integration of in situ field-effect transistors, X
      ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy
      measurements, and first-principles calculations, we identify that the electron
      doping from K adatoms drives bilayer WSe2 from a 2H phase semiconductor to a 1T'
      phase metal. The phase transition mechanism is satisfactorily explained by the
      electronic structures and energy alignment of the 2H and 1T' phases. This
      explanation can be generally applied to understand doping-induced phase
      transitions in two-dimensional (2D) structures. Finally, the associated dramatic
      changes of electronic structures and electrical conductance make this
      controllable semiconductor-metal phase transition of interest for 2D
      semiconductor-based electronic and optoelectronic devices.

PMID- 29369618
TI  - Microwave Spectra, Structure, and the Aromatic Character of 1-Chloroborepin.
AB  - High resolution microwave spectra for the somewhat unstable compound 1
      chloroborepin were measured in the 5-10 GHz range using a pulsed beam Fourier
      transform microwave spectrometer. Transitions were assigned and measured for
      three isotopologues, which include the most abundant isotopologue, 11B35Cl, and
      the less abundant 10B35Cl and 11B37Cl isotopologues. The molecular parameters
      (MHz) determined for the 11B35Cl isotopologue are A = 3490.905(35), B =
      1159.38520(79), C = 870.59492(56), 1.5chiaa (11B) = -0.220(22), 0.25(chibb -
      chicc) (11B) = -1.5300(99), 1.5chiaa (35Cl) = -54.572(33), and 0.25(chibb -
      chicc) (35Cl) = 4.7740(79). The inertial defect is calculated to be Delta = 
      0.174 amu A2 from the experimental rotational constants, indicating a planar
      structure with some out of plane vibrational motion. An extended Townes-Dailey
      analysis was performed on the 11B and 35Cl nuclei to determine the electron
      occupations in the valence hybridized orbitals using the experimental quadrupole
      coupling strengths. From the analysis it was determined that Cl is sharing some
      electron density with the empty p-orbital on B. The B-Cl bond length determined
      from the data is 1.798(1) A, and the B-C bond lengths are 1.533(10) A. The
      structural parameters and electronic structure properties of 1-chloroborepin are
      consistent with an aromatic boron-containing molecule.

PMID- 29369619
TI  - Exosomes-Small Players, Big Sound.
AB  - Incipiently named extracellular vesicles, exosomes are forming now a separate
      class of cellular mediators with important functions in physiological and
      pathological states. Their ability to transfer information between cells through
      encapsulation of proteins, nucleic acids and lipids for the preservation of the
      homeostatic equilibrium is translated also in pathological conditions. The
      recipient cells react to the reception of foreign molecules adjusting their
      molecular state according to the enclosed message. Cancer cells, in order to
      influence the microenvironment and facilitate the malignant expanding, exploit
      this intercellular trafficking. Immune cells are also producing exosomes that
      ensure the transportation of immune mediators and signaling molecules between
      cells. Current experimental attempts are concentrated on the adjustment of
      exosomes level for therapeutic purposes, enrolment of these vesicles as diagnosis
      or prognosis tools and also exosomes' use as drug delivery vehicles or immune
      stimulatory agents.

PMID- 29369620
TI  - Indium- and Zinc-Mediated Acyloxyallylation of Protected and Unprotected
      Aldotetroses-Revealing a Pronounced Diastereodivergence and a Fundamental
      Difference in the Performance of the Mediating Metal.
AB  - The acyloxyallylation of unprotected aldoses was first demonstrated more than a
      decade ago as a potentially elegant two-carbon homologation of reducing sugars
      (upon ozonolysis); however, its application in real case syntheses remained
      scarce. Following up on such a successful showcase and to answer several pending
      questions about this attractive transformation, we engaged in an in depth
      methodological reinvestigation. The epimeric tetroses l-erythrose and d-threose
      in unprotected and protected form were successfully applied to the indium and
      also zinc-mediated acyloxyallylation, with the latter being a first for an
      unprotected sugar. The investigation largely benefited from the choice of these
      more exotic starting materials as it allowed unambiguous
      identification/quantification of the hexose-products which are available as
      authentic reference materials. The observed diastereoselectivities indicate a
      strong substrate control (stereochemistry at O2), and the influence of the
      reagent's structure on the selectivity was investigated in great detail. A strong
      facial diastereodivergence between related protected and unprotected structures
      was demonstrated and an unexpected, pronounced principle difference in
      performance between indium and zinc was revealed.

PMID- 29369621
TI  - Robust Chemiresistive Sensor for Continuous Monitoring of Free Chlorine Using
      Graphene-like Carbon.
AB  - Free chlorine is widely used in industry as a bleaching and oxidizing agent. Its
      concentration is tightly monitored to avoid environmental contamination and
      deleterious human health effects. Here, we demonstrate a solid state
      chemiresistive sensor using graphene like carbon (GLC) to detect free chlorine in
      water. A 15-20 nm thick GLC layer on a PET substrate was modified with a redox
      active aniline oligomer (phenyl-capped aniline tetramer, PCAT) to increase
      sensitivity, improve selectivity, and impart fouling resistance. Both the bare
      GLC sensor and the PCAT-modified GLC sensor can detect free chlorine continuously
      and, unlike previous chemiresistive sensors, do not require a reset. The PCAT
      modified sensor showed a linear response with a slope of 13.89 (mg/L)-1 to free
      chlorine concentrations between 0.2 and 0.8 mg/L which is relevant for free
      chlorine monitoring for drinking water and wastewater applications. The PCAT
      modified GLC sensors were found to be selective and showed less than 0.5% change
      in current in response to species such as nitrates, phosphates and sulfates in
      water. They also were resistant to fouling from organic material and showed only
      a 2% loss in signal. Tap water samples from residential area were tested using
      this sensor which showed good agreement with standard colorimetric measurement
      methods. The GLC and PCAT-GLC sensors show high sensitivity and excellent
      selectivity to free chlorine and can be used for continuous automated monitoring
      of free chlorine.

PMID- 29369622
TI  - Modulation of the Electrochemical Reactivity of Solubilized Redox Active Polymers
      via Polyelectrolyte Dynamics.
AB  - Redox active polymers (RAPs) are electrochemically versatile materials that find
      key applications in energy storage, sensing, and surface modification. In spite
      of the ubiquity of RAP-modified electrodes, a critical knowledge gap exists in
      the understanding of the electrochemistry of soluble RAPs and their relation to
      polyelectrolyte dynamics. Here, we explore for the first time the intersection
      between polyelectrolyte behavior and the electrochemical response that highly
      soluble and highly substituted RAPs with viologen, ferrocene, and nitrostyrene
      moieties elicit at electrodes. This comprehensive study of RAP electrolytes over
      several orders of magnitude in concentration and ionic strength reveals distinct
      signatures consistent with surface confined, colloidal, and bulk-like
      electrochemical behavior. These differences emerge across polyelectrolyte packing
      regimes and are strongly modulated by changes in RAP coil size and electrostatic
      interactions with the electrode. We found that, unlike monomer motifs, simple
      changes in the ionic strength caused variations over 1 order of magnitude in the
      current measured at the electrode. In addition, the thermodynamics of adsorbed
      RAP films were also affected, giving rise to standard reduction potential shifts
      leading to redox kinetic effects as a result of the mediating nature of the RAP
      film in equilibrium with the solution. Full electrochemical characterization via
      transient and steady-state techniques, including the use of ultramicroelectrodes
      and the rotating disk electrode, were correlated to dynamic light scattering,
      ellipsometry, and viscometric analysis. These methods helped elucidate the
      relationship between electrochemical behavior and RAP coil size, film thickness,
      and polyelectrolyte packing regime. This study underscores the role of
      electrostatics in modulating the reactivity of redox polyelectrolytes.

PMID- 29369623
TI  - Linking 1D Transition-Metal Coordination Polymers and Different Inorganic Boron
      Oxides To Construct a Series of 3D Inorganic-Organic Hybrid Borates.
AB  - Three inorganic-organic hybrid borates, M(1,4-dab)[B5O7(OH)3] [M = Zn (1), Cd
      (2), 1,4-dab = 1,4-diaminobutane)] and Co(1,3-dap)[B4O7] (3, 1,3-dap = 1,3
      diaminopropane), which integrated characteristics of 1D coordination polymers and
      1D/3D inorganic boron oxides have been obtained under solvothermal conditions.
      Compounds 1 and 2 are isostructural and crystallize in a centrosymmetric space
      group P21/c; the 3D achiral structures of 1 and 2 consist of the nonhelical Zn/Cd
      1,4-dap coordination polymers and 1D B-O chains. Compound 3 crystallizes in a
      chiral space group P43212; the helical Co-1,3-dap coordination polymer chains are
      entrained within a 3D B-O network and finally form the chiral framework.
      Compounds 1-3 represent good examples of using coordination polymers to construct
      mixed-motif inorganic-organic hybrid borates. Compounds 1 and 2 display blue
      luminescence when excited with UV light.

PMID- 29369624
TI  - Heterogeneous Amyloid beta-Sheet Polymorphs Identified on Hydrogen Bond Promoting
      Surfaces Using 2D SFG Spectroscopy.
AB  - Two-dimensional sum-frequency generation spectroscopy (2D SFG) is used to study
      the structures of the pentapeptide FGAIL on hydrogen bond promoting surfaces.
      FGAIL is the most amyloidogenic portion of the human islet amyloid polypeptide
      (hIAPP or amylin). In the presence of a pure gold surface, FGAIL does not form
      ordered structures. When the gold is coated with a self-assembled monolayer of
      mercaptobenzoic acid (MBA), 2D SFG spectra reveal features associated with beta
      sheets. Also observed are cross peaks between the FGAIL peptides and the
      carboxylic acid groups of the MBA monolayer, indicating that the peptides are in
      close contact with the surface headgroups. In the second set of samples, FGAIL
      peptides chemically ligated to the MBA monolayer also exhibited beta-sheet
      features but with a much simpler spectrum. From simulations of the experiments,
      we conclude that the hydrogen bond promoting surface catalyzes the formation of
      both parallel and antiparallel beta-sheet structures with several different
      orientations. When ligated, parallel sheets with only a single orientation are
      the primary structure. Thus, this hydrogen bond promoting surface creates a
      heterogeneous distribution of polymorph structures, consistent with a
      concentration effect that allows nucleation of many different amyloid seeding
      structures. A single well-defined seed favors one polymorph over the others,
      showing that the concentrating influence of a membrane can be counterbalanced by
      factors that favor directed fiber growth. These experiments lay the foundation
      for the measurement and interpretation of beta-sheet structures with heterodyne
      detected 2D SFG spectroscopy. The results of this model system suggest that a
      heterogeneous distribution of polymorphs found in nature are an indication of
      nonselective amyloid aggregation whereas a narrow distribution of polymorph
      structures is consistent with a specific protein or lipid interaction that
      directs fiber growth.

PMID- 29369625
TI  - High-Throughput Assessment of Structural Continuity in Biologics.
AB  - We demonstrate a high-throughput chemoprinting platform that confirms the
      consistency in the higher-order structure of protein biologics and is sensitive
      enough to detect single-point mutations. This method addresses the quality and
      consistency of the tertiary and quaternary structure of biologic drug products,
      which is arguably the most important, yet rarely examined, parameter. The method
      described uses specific small-molecule ligands as molecular probes to assess
      protein structure. Each library of probe molecules provides a "fingerprint" when
      taken holistically. After proof-of-concept experiments involving enzymes and
      antibodies, we were able to detect minor conformational perturbations between
      four 48 kDa protein mutants that only differ by one amino acid residue.

PMID- 29369626
TI  - Unusually Short-Lived Solvent-Dependent Excited State in a Half-Sandwich Ru(II)
      Complex Induced by Low-Lying 3MC States.
AB  - A ruthenium complex with a half-sandwich geometry ([(p
      cymene)Ru(Cl)(curcuminoid)]) was synthesized, characterized, and investigated
      regarding its ultrafast photophysics. These photophysical investigations of the
      complex revealed a weak and short-lived emission from the initially populated
      1MLCT state and solvent-dependent photoinduced dynamics, where the secondarily
      populated 3MC state is stabilized by nonpolar solvents. Overall the decay of the
      3dd-MC state to the ground state is completed within picoseconds. This short
      excited-state lifetime is in stark contrast to the typically observed long-lived
      3MLCT states with lifetimes of nanoseconds or microseconds in unstrained,
      octahedral ruthenium complexes but is in good agreement with the findings for
      distorted octahedral complexes. This is pointing to the half-sandwich geometry as
      a new and easy approach to study these otherwise often concealed dd states.

PMID- 29369627
TI  - Polyoxometalate-Assisted, One-Pot Synthesis of a
      Pentakis[(triphenylphosphane)gold]ammonium(2+) Cation Containing Regular Trigonal
      Bipyramidal Geometries of Five Bonds to Nitrogen.
AB  - Novel intercluster compounds consisting of
      pentakis[(triphenylphosphane)gold]ammonium(2+) cation (1) and Keggin
      polyoxometalate (POM) anions, i.e., {[Au(PPh3)]5(MU5-N)}3[alpha-PM12O40]2 (1-PW
      for M = W; 1-PMo for M = Mo), were synthesized in 30-36% yield by one-pot
      reaction of the protonic acid form of the Keggin POMs, H3[alpha-PM12O40].nH2O (n
      = 13 for M = W; n = 15 for M = Mo) with monomeric (triphenylphosphane)gold(I)
      carboxylate [Au(RS-pyrrld)(PPh3)] [RS-Hpyrrld = (RS)-2-pyrrolidone-5-carboxylic
      acid] in the presence of aqueous NH3 at a molar ratio of 2:15:x (x = 3 for 1-PW;
      x = 7.5 for 1-PMo). These compounds resulted from the nitrogen-centered
      phosphanegold(I) clusterization of in situ generated monomeric phosphanegold(I)
      units, [Au(PPh3)]+ or [Au(L)(PPh3)]+ (L = NH3 or solvent), during the carboxylate
      elimination of [Au(RS-pyrrld)(PPh3)] in the presence of the Keggin POMs and
      aqueous NH3. The products 1-PW and 1-PMo were characterized by elemental
      analysis, Fourier transform infrared, thermogravimetric and differential thermal
      analyses (TGA/DTA), X-ray crystallography, and solid-state cross-polarization
      magic-angle-spinning (CPMAS) (31P and 15N) and solution (31P{1H} and 1H) NMR
      spectroscopy. The lattice contained three independent {[Au(PPh3)]5(MU5-N)}2+
      cations, of which two took regular trigonal-bipyramidal (TBP) geometries and the
      third took a distorted, square-pyramidal (SP) geometry. These geometries are in
      contrast to those reported by Schmidbaur's group for {[Au(PPh3)]5(MU5-N)}2+
      cations as BF4 salts. Density functional theory and ONIOM calculations for
      {[(L3P)Au]nN}(n-3)+ (L = H or Ph; n = 4-6) showed that the pentacoordinate
      cluster is energetically most stable and its TBP structure is only 1.6 kcal mol-1
      more stable than its SP structure, in accordance with the experimental facts.

PMID- 29369628
TI  - Green-Light-Sensitive BODIPY Photoprotecting Groups for Amines.
AB  - We describe a series of easily accessible, visible-light-sensitive (lambda > 500
      nm) BODIPY (boron-dipyrromethene)-based photoprotecting groups (PPGs) for primary
      and secondary amines, based on a carbamate linker. The caged compounds are stable
      under aqueous conditions for 24 h and can be efficiently uncaged in vitro with
      visible light (lambda = 530 nm). These properties allow efficient
      photodeprotection of amines, rendering these novel PPGs potentially suitable for
      various applications, including the delivery of caged drugs and their remote
      activation.

PMID- 29369629
TI  - Immolation of p-Aminobenzyl Ether Linker and Payload Potency and Stability
      Determine the Cell-Killing Activity of Antibody-Drug Conjugates with Phenol
      Containing Payloads.
AB  - The valine-citrulline (Val-Cit) dipeptide and p-aminobenzyl (PAB) spacer have
      been commonly used as a cleavable self-immolating linker in ADC design including
      in the clinically approved ADC, brentuximab vedotin (Adcetris). When the same
      linker was used to connect to the phenol of the cyclopropabenzindolone (CBI)
      (P1), the resulting ADC1 showed loss of potency in CD22 target-expressing cancer
      cell lines (e.g., BJAB, WSU-DLCL2). In comparison, the conjugate (ADC2) of a
      cyclopropapyrroloindolone (CPI) (P2) was potent despite the two corresponding
      free drugs having similar picomolar cell-killing activity. Although the
      corresponding spirocyclization products of P1 and P2, responsible for DNA
      alkylation, are a prominent component in buffer, the linker immolation was slow
      when the PAB was connected as an ether (PABE) to the phenol in P1 compared to
      that in P2. Additional immolation studies with two other PABE-linked substituted
      phenol compounds showed that electron-withdrawing groups accelerated the
      immolation to release an acidic phenol-containing payload (to delocalize the
      negative charge on the anticipated anionic phenol oxygen during immolation). In
      contrast, efficient immolation of LD4 did not result in an active ADC4 because
      the payload (P4) had a low potency to kill cells. In addition, nonimmolation of
      LD5 did not affect the cell-killing potency of its ADC5 since immolation is not
      required for DNA alkylation by the center-linked pyrrolobenzodiazepine.
      Therefore, careful evaluation needs to be conducted when the Val-Cit-PAB linker
      is used to connect antibodies to a phenol-containing drug as the linker
      immolation, as well as payload potency and stability, affects the cell-killing
      activity of an ADC.

PMID- 29369630
TI  - Sterols in Infant Formulas: A Bioaccessibility Study.
AB  - The design of infant formulas (IFs) seeks to resemble human milk (HM) composition
      and functionality. The fat sources used usually comprise vegetable oil blends to
      mimic the fatty acid composition of HM and introduce changes in the animal/plant
      sterol ratio. In contrast, the use of milk fat globule membrane (MFGM)-rich
      ingredients could improve this aspect by increasing the ratio. The present study
      evaluates the bioaccessibility (BA) of sterols (cholesterol, desmosterol,
      brassicasterol, campesterol, stigmasterol, and beta-sitosterol) in three IFs
      (with or without MFGM) using an in vitro digestion method simulating infant
      conditions. Analytical parameters confirmed the suitability of the method for all
      of these sterols. Results showed the presence of MFGM to increase cholesterol
      content (6-7 vs 2 mg/100 mL), this being the most bioaccessible sterol in the
      IFs. Although the BA of cholesterol was reduced in MFGM-enriched IF (65.6-80.4%
      vs 99.7%), the intake of bioaccessible cholesterol from these IFs was higher.

PMID- 29369631
TI  - Comparison of Interfacial Electron Transfer Efficiency in [Fe(ctpy)2]2+-TiO2 and
      [Fe(cCNC)2]2+-TiO2 Assemblies: Importance of Conformational Sampling.
AB  - Fe(II)-polypyridines have limited applications as chromophores in dye-sensitized
      solar cells due to the short lifetimes (~100 fs) of their photoactive metal-to
      ligand charge transfer (MLCT) states formed upon photoexcitation. Recently, a 100
      fold increase in the MLCT lifetime was observed in a [Fe(CNC)2]2+ complex (CNC =
      2,6-bis(3-methylimidazole-1-ylidine)pyridine) which has strong sigma-donating N
      heterocyclic carbene ligand in comparison to the weaker field parent [Fe(tpy)2]2+
      complex (tpy = 2,2':6',2"-terpyridine). This study utilizes density functional
      theory (DFT), time-dependent DFT, and quantum dynamics simulations to investigate
      the interfacial electron transfer (IET) in [Fe(cCNC)2]2+ (cCNC = 4'-carboxy-2,6
      bis(3-methylimidazole-1-ylidine)pyridine) and [Fe(ctpy)2]2+ (ctpy = 4'-carboxy
      2,2':6',2"-terpyridine) sensitized TiO2. Our results suggest that the replacement
      of tpy by CNC ligand does not significantly speed up the IET kinetics in the
      [Fe(cCNC)2]2+-TiO2 assembly in comparison to the [Fe(ctpy)2]2+-TiO2 analogue. The
      high IET efficiency in the [Fe(cCNC)2]2+-TiO2 assemblies is therefore due to
      longer lifetime of [Fe(cCNC)2]2+ photoactive 3MLCT states rather than faster
      electron injection kinetics. It was also found that the inclusion of
      conformational sampling in the computational model is important for proper
      description of the IET processes in these systems, as the models relying on the
      use of only fully optimized structures may yield misleading results. The
      simulations presented in this work also illustrate various pitfalls of utilizing
      properties such as electronic coupling, number of available acceptor states, and
      driving force, as well as calculations based on Fermi's golden rule framework, to
      reach conclusions on the IET efficiency in dye-semiconductor systems.

PMID- 29369632
TI  - Magnetic-Field-Dependent Lifetimes of Hyperpolarized 13C Spins at Cryogenic
      Temperature.
AB  - Using a home-built cryogen-free dynamic nuclear polarization (DNP) system with a
      variable magnetic field capability, 13C spin-lattice T1 relaxation times of
      hyperpolarized [1-13C] carboxylates (sodium acetate, glycine, sodium pyruvate,
      and pyruvic acid) doped with trityl OX063 free radical were systematically
      measured for the first time at different field strengths up to 9 T at T = 1.8 K.
      Our data reveal that the 13C T1 values of these frozen hyperpolarized 13C samples
      vary drastically with the applied magnetic field B according to an apparent
      empirical power-law dependence (13C T1 ? Balpha, 2.3 < alpha < 3.1), with
      relaxation values ranging from a few hundred seconds at 1 T to over 200,000 s at
      fields close to 9 T. This low temperature relaxation behavior can be ascribed
      approximately to a model that accounts for the combined effect of 13C-1H
      intramolecular dipolar interaction and the relaxation contribution from the
      paramagnetic impurities present in the DNP sample. Since the lifetime or T1
      storage of the hyperpolarized state is intimately linked to DNP efficiency, these
      13C relaxation data at cryogenic temperature have important theoretical and
      experimental implications as the DNP of 13C-labeled biomolecules is pushed to
      higher magnetic fields.

PMID- 29369633
TI  - In Situ Investigation of Defect-Free Copper Nanowire Growth.
AB  - The fabrication and placement of high purity nanometals, such as one-dimensional
      copper (Cu) nanowires, for interconnection in integrated devices have been among
      the most important technological developments in recent years. Structural
      stability and oxidation prevention have been the key issues, and the defect
      control in Cu nanowire growth has been found to be important. Here, we report the
      synthesis of defect-free single-crystalline Cu nanowires by controlling the
      surface-assisted heterogeneous nucleation of Cu atomic layering on the graphite
      like loop of an amorphous carbon (a-C) lacey film surface. Without a metal
      catalyst or induced defects, the high quality Cu nanowires formed with high
      aspect ratio and high growth rate of 578 nm/s. The dynamic study of the growth of
      heterogeneous nanowires was conducted in situ with a high-resolution transmission
      electron microscope. The study illuminates the new mechanism by heterogeneous
      nucleation control and laying the groundwork for better understanding of
      heterosurface-assisted nucleation of defect-free Cu nanowire on a-C lacey film.

PMID- 29369634
TI  - Blue-Shifting Intramolecular Charge Transfer Emission by Nonlocal Effect of
      Hyperbolic Metamaterials.
AB  - Metallic nanostructures permit controlling various photophysical processes by
      coupling photons with plasmonic oscillation of electrons confined in the tailored
      nanostructures. One example is hyperbolic metamaterial (HMM) leading to an
      enhanced spontaneous emission rate of emitters located nearby. Noting that
      emission in organic molecules is from either pi-pi* or intramolecular charge
      transfer (ICT) states, we address here how HMM modifies ICT emission spectral
      features by comparing them with a spectral shift dependent on the local polarity
      of the medium. The 7.0 nm blue shift is observed in ICT emission from 4
      dicyanomethylene-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran dispersed into a
      polymer matrix prepared on HMM multilayered structure, while no spectral shift is
      observed in pi-pi* emission from perylene diimide. In the frame of the Lippert
      Mataga formalism, the blue shift is explained by the HMM nonlocal effects
      resulting from 8% decrease in refractive index and 18% reduction in dielectric
      permittivity. This phenomenon was also shown in a hemicurcuminoid borondifluoride
      dye yielding 15.0 nm blue shift. Such a capability of spectral shift control in
      films by HMM structure opens new prospects for engineering organic light-emitting
      devices.

PMID- 29369635
TI  - Unusual Indirect Nuclear Spin-Spin Exchange Coupling through Solvated Electron.
AB  - Solvated electrons have been found to exist in various media which also exhibit
      more intriguing properties such as superconductivity, nonlinear optical response,
      and so on. However, how they affect the nuclear spin properties has not been
      proven. In this work, we present the first detailed study on solvated-electron
      triggered indirect nuclear spin-spin J-coupling using density functional theory
      calculations. Taking 19F as a probe, we verify the presence of unusual J
      couplings between two distant F atoms in HF-containing anionic clusters. These
      couplings occur "through solvated electron", rather than through conventional
      covalent bonds or space. Solvated electron can serve as an additional channel to
      efficiently realize long-range J-coupling between far separated nuclei because of
      its dispersivity and Rydberg character. The coupling magnitude strongly depends
      on the unique distribution of solvated electron and its second-order interaction
      with solvating HF units. This work provides novel insights into the mediating
      roles of electrons, possibly opening up potential applications based on weakly
      bound electrons.

PMID- 29369636
TI  - Mass Spectrometry Using Nanomechanical Systems: Beyond the Point-Mass
      Approximation.
AB  - The mass measurement of single molecules, in real time, is performed routinely
      using resonant nanomechanical devices. This approach models the molecules as
      point particles. A recent development now allows the spatial extent (and, indeed,
      image) of the adsorbate to be characterized using multimode measurements ( Hanay
      , M. S. , Nature Nanotechnol. , 10 , 2015 , pp 339 - 344 ). This "inertial
      imaging" capability is achieved through virtual re-engineering of the resonator's
      vibrating modes, by linear superposition of their measured frequency shifts.
      Here, we present a complementary and simplified methodology for the analysis of
      these inertial imaging measurements that exhibits similar performance while
      streamlining implementation. This development, together with the software that we
      provide, enables the broad implementation of inertial imaging that opens the door
      to a range of novel characterization studies of nanoscale adsorbates.

PMID- 29369638
TI  - Signatures of Conformational Dynamics and Electrode-Molecule Interactions in the
      Conductance Profile During Pulling of Single-Molecule Junctions.
AB  - We demonstrate that conductance can act as a sensitive probe of conformational
      dynamics and electrode-molecule interactions during the equilibrium and
      nonequilibrium pulling of molecular junctions. To do so, we use a combination of
      classical molecular dynamics simulations and Landauer electron transport
      computations to investigate the conductance of a family of Au-alkanedithiol-Au
      junctions as they are mechanically elongated. The simulations show an overall
      decay of the conductance during pulling that is due to a decrease in the through
      space electrode-molecule interactions, and that sensitivity depends on the
      electrode geometry. In addition, characteristic kinks induced by level alignment
      shifts (and to a lesser extent by quantum destructive interference) were also
      observed superimposed to the overall decay during pulling simulations. The latter
      effect depends on the variation of the molecular dihedral angles during pulling
      and therefore offers an efficient solution to experimentally monitor
      conformational dynamics at the single-molecule limit.

PMID- 29369637
TI  - Dynamics of Zebrafish Heart Regeneration Using an HPLC-ESI-MS/MS Approach.
AB  - Failure to properly repair damaged due to myocardial infarction is a major cause
      of heart failure. In contrast with adult mammals, zebrafish hearts show
      remarkable regenerative capabilities after substantial damage. To characterize
      protein dynamics during heart regeneration, we employed an HPLC-ESI-MS/MS (mass
      spectrometry) approach. Myocardium tissues were taken from sham-operated fish and
      ventricle-resected sample at three different time points (2, 7, and 14 days);
      dynamics of protein expression were analyzed by an ion-current-based quantitative
      platform. More than 2000 protein groups were quantified in all 16 experiments.
      Two hundred and nine heart-regeneration-related protein groups were quantified
      and clustered into six time-course patterns. Functional analysis indicated that
      multiple molecular function and metabolic pathways were involved in heart
      regeneration. Interestingly, Ingenuity Pathway Analysis revealed that P53
      signaling was inhibited during the heart regeneration, which was further verified
      by real-time quantitative polymerase chain reaction (Q-PCR). In summary, we
      applied systematic proteomics analysis on regenerating zebrafish heart, uncovered
      the dynamics of regenerative genes expression and regulatory pathways, and
      provided invaluable insight into design regenerative-based strategies in human
      hearts.

PMID- 29369639
TI  - Correlating Nanoscopic Energy Transfer and Far-Field Emission to Unravel Lasing
      Dynamics in Plasmonic Nanocavity Arrays.
AB  - Excited-state interactions between nanoscale cavities and photoactive molecules
      are critical in plasmonic nanolasing, although the underlying details are less
      resolved. This paper reports direct visualization of the energy-transfer dynamics
      between two-dimensional arrays of plasmonic gold bowtie nanocavities and dye
      molecules. Transient absorption microscopy measurements of single bowties within
      the array surrounded by gain molecules showed fast excited-state quenching (2.6
      +/- 1 ps) characteristic of individual nanocavities. Upon optical pumping at
      powers above threshold, lasing action emerged depending on the spacing of the
      array. By correlating ultrafast microscopy and far-field light emission
      characteristics, we found that bowtie nanoparticles acted as isolated cavities
      when the diffractive modes of the array did not couple to the plasmonic gap mode.
      These results demonstrate how ultrafast microscopy can provide insight into
      energy relaxation pathways and, specifically, how nanocavities in arrays can show
      single-unit nanolaser properties.

PMID- 29369640
TI  - Observation of Tunable Charged Exciton Polaritons in Hybrid Monolayer WS2
      Plasmonic Nanoantenna System.
AB  - Formation of dressed light-matter states in optical structures, manifested as
      Rabi splitting of the eigen energies of a coupled system, is one of the key
      effects in quantum optics. In pursuing this regime with semiconductors, light is
      usually made to interact with excitons, electrically neutral quasiparticles of
      semiconductors; meanwhile interactions with charged three-particle states,
      trions, have received little attention. Here, we report on strong interaction
      between localized surface plasmons in silver nanoprisms and excitons and trions
      in monolayer tungsten disulfide (WS2). We show that the plasmon-exciton
      interactions in this system can be efficiently tuned by controlling the charged
      versus neutral exciton contribution to the coupling process. In particular, we
      show that a stable trion state emerges and couples efficiently to the plasmon
      resonance at low temperature by forming three bright intermixed plasmon-exciton
      trion polariton states. Our findings open up a possibility to exploit
      electrically charged polaritons at the single nanoparticle level.

PMID- 29369641
TI  - Nonreciprocal Flat Optics with Silicon Metasurfaces.
AB  - Metasurfaces enable almost complete control of light through ultrathin,
      subwavelength surfaces by locally and abruptly altering the scattered phase. To
      date, however, all metasurfaces obey time-reversal symmetry, meaning that forward
      and backward traveling waves will trace identical paths when being reflected,
      refracted, or diffracted. Here, we use full-field calculations to design a
      passive metasurface for nonreciprocal transmission of both direct and anomalously
      refracted near-infrared light over nanoscale optical path lengths. The
      metasurface consists of a 100 nm-thick, periodically patterned Si slab. Owing to
      the high-quality-factor resonances of the metasurface and the inherent Kerr
      nonlinearities of Si, this structure acts as an optical diode for free-space
      optical signals. This structure also exhibits nonreciprocal anomalous refraction
      with appropriate patterning to form a phase gradient metasurface. Compared to
      existing schemes for breaking time-reversal symmetry, our platform enables
      subwavelength nonreciprocity for arbitrary free-space optical inputs and provides
      a straightforward path to experimental realization. The concept is also
      generalizable to other metasurface functions, providing a foundation for one-way
      lensing and holography.

PMID- 29369642
TI  - Copper-Catalyzed Fluoroolefination of Silyl Enol Ethers and Ketones toward the
      Synthesis of beta-Fluoroenones.
AB  - A general and facile synthetic method for beta-fluoroenones from silyl enol
      ethers or ketones, with a copper-amine catalyst system, has been developed. The
      reaction proceeded by a tandem process of difluoroalkylation-hydrolysis
      dehydrofluorination. This method is characterized by high yields, excellent Z/E
      ratios, a low-cost catalyst, and a broad substrate scope. The synthetic potential
      of beta-fluoroenones has been demonstrated by the construction of various
      complicated organofluorine molecules.

PMID- 29369643
TI  - When reality is out of focus: Can people tell whether their beliefs and judgments
      are correct or wrong?
AB  - Can we tell whether our beliefs and judgments are correct or wrong? Results
      across many domains indicate that people are skilled at discriminating between
      correct and wrong answers, endorsing the former with greater confidence than the
      latter. However, it has not been realized that because of people's adaptation to
      reality, representative samples of items tend to favor the correct answer,
      yielding object-level accuracy (OLA) that is considerably better than chance.
      Across 16 experiments that used 2-alternative forced-choice items from several
      domains, the confidence/accuracy (C/A) relationship was positive for items with
      OLA >50%, but consistently negative across items with OLA <50%. A systematic
      sampling of items that covered the full range of OLA (0-100%) yielded a U
      function relating confidence to OLA. The results imply that the positive C/A
      relationship that has been reported in many studies is an artifact of OLA being
      better than chance rather than representing a general ability to discriminate
      between correct and wrong responses. However, the results also support the
      ecological approach, suggesting that confidence is based on a frugal, "bounded"
      heuristic that has been specifically tailored to the ecological structure of the
      natural environment. This heuristic is used despite the fact that for items with
      OLA <50%, it yields confidence judgments that are counterdiagnostic of accuracy.
      Our ability to tell between correct and wrong judgments is confined to the
      probability structure of the world we live in. The results were discussed in
      terms of the contrast between systematic design and representative design.
      (PsycINFO Database Record

PMID- 29369644
TI  - Moving beyond summary scores: Decomposing free recall performance to understand
      episodic memory deficits in schizotypy.
AB  - Negative symptom schizophrenia and negative schizotypy are associated with
      deficits in episodic memory, which may reflect deficits in context processing.
      However, studies that rely on summary performance measures such as mean accuracy
      or latency are limited in the extent that they can examine processes underlying
      memory impairment. The present study decomposed free recall performance by
      examining serial position functions, first response probability, temporal
      contiguity effect, cumulative recall functions, and interresponse times in high
      positive schizotypy, high-negative schizotypy, and control groups. The negative
      schizotypy group exhibited not only impaired overall free recall performance but
      also a pattern of deficits consistent with impaired context processing on the
      underlying measures. Specifically, the negative schizotypy group was less likely
      than the other groups to initiate recall with the first item in the list,
      suggesting impaired encoding or reinstatement of context, and also showed reduced
      temporal contiguity compared with the other groups, suggesting diminished
      temporal organization. The cumulative recall function indicated that the negative
      schizotypy group experienced disruptions in both the sampling and recovery stages
      of retrieval. Finally, the negative schizotypy group experienced greater slowing
      between the responses during retrieval, consistent with the finding of reduced
      temporal contiguity and indicating that it likely terminated memory search before
      the remaining groups. The positive schizotypy and control groups did not differ
      on any of the measures. The finding that context-processing deficits occur in
      both subclinical negative schizotypy and negative symptom schizophrenia suggests
      that they may represent core areas of impairment in the schizophrenia spectrum.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29369645
TI  - Biological motion sensitivity, but not interpersonal predictive coding is
      impaired in schizophrenia.
AB  - Social predictive coding is now a well-established phenomenon in healthy
      individuals. It has been demonstrated that the communicative gestures of one
      agent may be effectively used to predict the actions of other agents. Individuals
      with schizophrenia often present social-cognitive deficits. The aim of this paper
      is to examine interpersonal predictive coding in patients with schizophrenia.
      Forty-six participants with schizophrenia and 40 healthy controls (HC) completed
      a simultaneous masking detection task (Interpersonal Detection Task; IDT), during
      which they observed point-light displays of two agents (A and B). During the
      communicative condition, agent A performed a communicative gesture, to which
      agent B responded accordingly. During the individual condition, agent A performed
      a noncommunicative action instead of the communicative gesture. Upon completion
      of the IDT, participants were asked to explicitly classify the actions of two
      agents based on nonmasked videos of point-light dyads. In line with previous
      findings, people with schizophrenia presented a reduced masking threshold for
      biological motion displays, and were less able to correctly recognize the actions
      of two agents during the explicit recognition task. However, observing the
      communicative gesture of agent A enhanced the visual discrimination of agent B in
      participants from all groups. This effect was observed despite the fact that SCZ
      presented overall diminished sensitivity to biological motion during IDT.
      Interpersonal predictive coding, which at least partially relies upon implicit
      processes, may be less impaired in people with schizophrenia than explicit social
      cognitive processes (e.g., theory of mind). (PsycINFO Database Record

PMID- 29369646
TI  - Setting the alarm: Word emotional attributes require consolidation to be
      operational.
AB  - Demonstrations of emotional Stroop in conditioned made-up words are flawed
      because of the lack of task ensuring similar word encoding across conditions.
      Here, participants were trained on associations between made-up words (e.g.,
      'drott') and pictures with an alarming or neutral content (e.g., 'a dead sheep'
      vs. 'a munching cow') in a situation that required attention to both ends of each
      association. To test whether word emotional attributes need to consolidate before
      they can hijack attention, one set of associations was learned seven days before
      the test, whereas the other set was learned either six hrs or immediately before
      the test. The novel words' ability to evoke their emotional attributes was
      assessed by using both Stroop and an auditory analogue called pause detection.
      Matching words and pictures was harder for alarming associations. However,
      similar learning rate and forgetting at seven days were observed for both types
      of associations. Pause detection revealed no emotion effect for same-day (i.e.,
      unconsolidated) associations, but robust interference for seven-day-old (i.e.,
      consolidated) alarming associations. Attention capture was found in the emotional
      Stroop as well, though only when trial n-1 referred to a same-day association.
      This task also showed stronger response repetition priming (independently of
      emotion) when trials n and n-1 both tapped into seven-day-old associations. Word
      emotional attributes hence take between six hrs and seven days to be operational.
      Moreover, age interactions between consecutive trials can be used to gauge
      implicitly the indirect (relational) episodic associations that develop in the
      meantime between the memories of individual items. (PsycINFO Database Record (c)
      2018 APA, all rights reserved).

PMID- 29369647
TI  - Health policy brief: Global mental health and the United Nations' sustainable
      development goals.
AB  - INTRODUCTION: Increased awareness of the importance of mental health for global
      health has led to a number of new initiatives, including influential policy
      instruments issued by the World Health Organization (WHO) and the United Nations
      (UN). METHOD: This policy brief describes two WHO instruments, the Mental Health
      Action Plan for 2013-2020 (World Health Organization, 2013) and the Mental Health
      Atlas (World Health Organization, 2015), and presents a comparative analysis with
      the Sustainable Development Goals (SDGs) of the UN's 2030 Agenda for Sustainable
      Development (United Nations, 2015). RESULTS: The WHO's Action Plan calls for
      several specific objectives and targets, with a focus on improving global mental
      health governance and service coverage. In contrast, the UN's Sustainable
      Development Goals include only one goal specific to mental health, with a single
      indicator tracking suicide mortality rates. DISCUSSION: The discrepancy between
      the WHO and UN frameworks suggests a need for increased policy coherence.
      Improved global health governance can provide the basis for ensuring and
      accelerating progress in global mental health. (PsycINFO Database Record

PMID- 29369648
TI  - Achieving same-day access in integrated primary care.
AB  - Same-day access to behavioral health services is a critical feature of integrated
      primary care. Despite the benefits of same-day access, implementing and
      sustaining this key feature has been a challenge for multiple health care
      settings. Further, there is relatively little practical guidance on how to
      implement this practice management feature. Diverse program design solutions for
      same-day access are implemented in clinics across the Veterans Health
      Administration. The authors identified innovative approaches, developed in local
      facilities, with demonstrated success in same-day access that can be implemented
      in any setting. The purpose of this article is to describe five approaches for
      providing same-day access within integrated care. The authors discuss key
      considerations (staffing, space, program maturity), potential challenges and
      facilitators, and provide practical recommendations for implementation. (PsycINFO
      Database Record

PMID- 29369649
TI  - A review of published guidance for video recording in medical education.
AB  - INTRODUCTION: Medical educators have used resident-patient video recording to
      verify trainee competence in interpersonal and technical skills for 50 years.
      Although numerous authors acknowledge that video recording can compromise patient
      privacy and confidentiality, no summary of potential risks is available. METHOD:
      A scoping review of the literature on resident-patient video recording in medical
      education from the 1960s to the present was conducted. The review examined
      publications that addressed ethical, policy, procedural, or legal issues
      affecting patients' rights when video recording. RESULTS: Potential risks to the
      rights of video recorded patients were organized into 6 categories: informed
      consent policies, informed consent procedures, recorded medical errors, secondary
      use of recordings, collateral patient information, and public trust issues. The
      review revealed contradictory opinions on informed consent policies, inadequate
      guidance for responding when medical errors are recorded, and conflicting
      opinions about when recordings become part of the medical record. Many reviewed
      publications are opinion-based, precede current confidentiality guidelines, or
      rely on survey results. DISCUSSION: This review organizes potential threats to
      patients' rights for those medical educators who use video recording technology.
      The review reveals a need for broader consensus about video recording guidelines
      and for research on video recording practices, especially given technological
      advances in video equipment and the expansion of video technology in health care
      settings. (PsycINFO Database Record

PMID- 29369650
TI  - Parental attitudes following disclosure of sibling sexual abuse: A child advocacy
      center intervention study.
AB  - Sibling sexual abuse (SSA) represents a range of childhood sexual behaviors that
      cannot be considered manifestations of age-appropriate curiosity. Despite being
      the commonest and longest lasting form of sexual abuse within the family, SSA is
      the least reported, treated, and researched. This qualitative study is based on a
      sample of 60 mostly religious Jewish families referred to a child advocacy center
      (CAC) in Jerusalem from 2010 to 2015. It examines parental attitudes to SSA and
      their reconstruction, during and after their experience at the CAC. Analysis of
      case summaries and documented conversations between child protection officers and
      parents reveals 2 main initial parental attitudes after the disclosure SSA. The
      first is the attitude that no sexual acts took place at all. The second is that
      they did occur, with 3 different variations: the sexual acts as "not serious," as
      a "rupture in the family's ideal narrative," and as "another tragic episode in
      the family's tragic life story." Findings also suggest that the CAC intervention
      is a turning point, leading most parents to reconstruct their initial attitudes
      from "never happened" or "not serious" to "rupture in the family image" or to
      "another negative event in the family." These findings underscore the need to
      study the experiences of parents whose children were involved in SSA to inform
      policy, treatment and research. This is critical, as interventions that are not
      aligned with family attitudes and needs are known to exacerbate the family
      crisis. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 29369651
TI  - Trauma proliferation and stress generation (TPSG) dynamics and their implications
      for clinical science.
AB  - The current research and clinical focus on single traumas fails to assess
      numerous important trauma dynamics including trauma proliferation. In this study,
      2 trauma proliferation pathways were identified that utilize a developmentally
      based trauma framework (DBTF). Data previously collected from 6 different
      cultural groups (N = 2279; 2 mental health clinics in Egypt and the United
      States, Native Americans, Palestinian adults in Gaza, and college students in
      Poland and Egypt) were reanalyzed. The 6 studies utilized DBTF-based measures of
      cumulative trauma and trauma types. Path analysis was used to test the trauma
      proliferation model and PROCESS software was used to identify mediators and their
      effect sizes. Results of the analyses indicated that attachment trauma and
      collective identity trauma independently predicted (directly and through
      mediators) personal identity trauma, role identity trauma, secondary trauma, and
      survival trauma. The pattern of proliferation was configurally invariant across
      the 6 groups and strictly invariant across genders. Implications for the
      consideration of trauma global dynamics, such as trauma proliferation, are
      discussed. (PsycINFO Database Record

PMID- 29369652
TI  - Experiences of peer exclusion and victimization, cognitive functioning, and
      depression among adolescent cancer survivors in South Korea.
AB  - Adolescents who reenter school after treatment for cancer may face certain
      challenges, such as social exclusion by their peers and difficulties in cognitive
      functioning, due to the cancer treatment and its psychosocial sequelae. Such
      challenges may have an impact on their mental health. This cross-sectional study
      examined the impact of peer exclusion-victimization and cognitive functioning on
      depression among adolescent survivors of childhood cancer. A total of 175
      adolescent survivors of childhood cancer between the ages of 13 and 19 years
      completed a self-reported questionnaire. Their mean age was 15.33 years (SD =
      1.65), the mean time since diagnosis was 7.97 years (SD = 3.91), and 49.7%
      experienced at least 1 kind of peer exclusion in school. Multiple regression
      analysis was conducted to examine the effects of survivors' experiences related
      to peer exclusion-victimization and cognitive functioning on depression,
      controlling for demographic (age and gender) and cancer-related (cancer type,
      time since diagnosis, recurrence) characteristics. The model with peer exclusion
      victimization and cognitive functioning as predictors accounted for 27.9% of the
      variance in depression. More experiences in peer exclusion-victimization (beta =
      .200, p = .024) and lower cognitive functioning (beta = -.465, p < .001) were
      associated with greater levels of depression. Understanding the impact of
      survivors' experiences of peer exclusion-victimization and cognitive functioning
      on their mental health will help professionals to provide appropriate counseling
      services to moderate peer exclusion-victimization as well as resources for
      academic performance for those cancer survivors at risk for depression. (PsycINFO
      Database Record

PMID- 29369653
TI  - Using beta coefficients to impute missing correlations in meta-analysis research:
      Reasons for caution.
AB  - Meta-analysis has become a well-accepted method for synthesizing empirical
      research about a given phenomenon. Many meta-analyses focus on synthesizing
      correlations across primary studies, but some primary studies do not report
      correlations. Peterson and Brown (2005) suggested that researchers could use
      standardized regression weights (i.e., beta coefficients) to impute missing
      correlations. Indeed, their beta estimation procedures (BEPs) have been used in
      meta-analyses in a wide variety of fields. In this study, the authors evaluated
      the accuracy of BEPs in meta-analysis. We first examined how use of BEPs might
      affect results from a published meta-analysis. We then developed a series of
      Monte Carlo simulations that systematically compared the use of existing
      correlations (that were not missing) to data sets that incorporated BEPs (that
      impute missing correlations from corresponding beta coefficients). These
      simulations estimated rho (mean population correlation) and SDrho (true standard
      deviation) across a variety of meta-analytic conditions. Results from both the
      existing meta-analysis and the Monte Carlo simulations revealed that BEPs were
      associated with potentially large biases when estimating rho and even larger
      biases when estimating SDrho. Using only existing correlations often
      substantially outperformed use of BEPs and virtually never performed worse than
      BEPs. Overall, the authors urge a return to the standard practice of using only
      existing correlations in meta-analysis. (PsycINFO Database Record

PMID- 29369654
TI  - Why and when hierarchy impacts team effectiveness: A meta-analytic integration.
AB  - Hierarchy has the potential to both benefit and harm team effectiveness. In this
      article, we meta-analytically investigate different explanations for why and when
      hierarchy helps or hurts team effectiveness, drawing on results from 54 prior
      studies (N = 13,914 teams). Our findings show that, on net, hierarchy negatively
      impacts team effectiveness (performance: rho = -.08; viability: rho = -.11), and
      that this effect is mediated by increased conflict-enabling states. Additionally,
      we show that the negative relationship between hierarchy and team performance is
      exacerbated by aspects of the team structure (i.e., membership instability, skill
      differentiation) and the hierarchy itself (i.e., mutability), which make
      hierarchical teams prone to conflict. The predictions regarding the positive
      effect of hierarchy on team performance as mediated by coordination-enabling
      processes, and the moderating roles of several aspects of team tasks (i.e.,
      interdependence, complexity) and the hierarchy (i.e., form) were not supported,
      with the exception that task ambiguity enhanced the positive effects of
      hierarchy. Given that our findings largely support dysfunctional views on
      hierarchy, future research is needed to understand when and why hierarchy may be
      more likely to live up to its purported functional benefits. (PsycINFO Database
      Record

PMID- 29369655
TI  - Early parental loss and intimate relationships in adulthood: A nationwide study.
AB  - Being able to form and maintain intimate relationships is an essential part of
      development and the early loss of a parent may negatively affect this ability.
      This study investigates the association between parental loss before the age of
      18 years and the formation and dissolution of marriage and cohabitation
      relationships in adulthood, in relation to factors that may help identify
      potentially vulnerable subgroups of bereaved children, that is, sex of the
      deceased parent, cause of death and child's age at the time of death. Using data
      from national registries, we followed all children born in Denmark between 1970
      and 1995 (n = 1,525,173) and used Poisson regression models to assess rate ratios
      by gender for relationship formation and separation according to early parental
      loss. We stratified the analyses by sex of the deceased parent, cause of death
      and child's age at the time of death, and adjusted for the confounding effects of
      parental income, education level, and psychiatric illness. We found that parental
      loss was associated with a higher rate of relationship formation for young women,
      but not young men, and higher rates of separation for both men and women. The
      associations with separation were stronger for persons who lost a parent to
      suicide than to other causes. The effects were relatively small, a possible
      testimony to the resilience of developmental processes in most children. However,
      as long-term relationships are associated with physical and psychological health,
      interventions for bereaved children and families are important, especially in the
      subgroup bereaved by suicide. (PsycINFO Database Record

PMID- 29369656
TI  - Secure base script and psychological dysfunction in Japanese young adults in the
      21st century: Using the Attachment Script Assessment.
AB  - The universality of secure base construct, which suggests that one's use of an
      attachment figure as a secure base from which to explore the environment is an
      evolutionary outcome, is one of the core ideas of attachment theory. However,
      this universality idea has been critiqued because exploration is not as valued in
      Japanese culture as it is in Western cultures. Waters and Waters (2006)
      hypothesized that one's experiences of secure base behaviors are stored as a
      script in memory, and developed a narrative assessment called the Attachment
      Script Assessment (ASA) to evaluate one's secure base script. This study examined
      the validity of the ASA and the utility of secure base concept in Japanese
      culture. A sample of Japanese young adults (N = 89; M = 23.46; SD = 3.20; 57% =
      females) completed both the ASA and self-report questionnaires. The results
      revealed that the ASA score was associated with two dimensions of self-report
      questionnaires assessing parent-youth attachment relationships (trust and
      communication). The ASA score was not related to Japanese cultural values (amae
      acceptance, interdependent self-construal, and low independent self-construal).
      However, a low ASA score was related to a psychological dysfunction in the
      Japanese cultural context; hikikomori symptoms, which are defined as a desire to
      remain in his or her own room and his or her understanding of this behavior in
      other people. We concluded that since hikikomori can be interpreted as an extreme
      inhibition of exploration, the association between low secure base script and
      hikikomori symptoms suggests the utility of secure base construct in Japan.
      (PsycINFO Database Record

PMID- 29369658
TI  - Lesbian, Gay, and Transgender Veterans' Experiences in the Veterans Health
      Administration: Positive Signs and Room for Improvement.
AB  - This study explored the characteristics of lesbian, gay, and transgender veteran
      users of Veterans Health Administration (VHA) services and nonusers, using a
      national convenience sample. Participants responded to an online, anonymous
      survey posted on LGBT websites and forwarded through personal contacts, using a
      snow-ball sampling strategy, resulting in a final sample of 218. Most
      participants were enrolled in VHA (n = 151). VHA users were older, more
      ethnically diverse, had less income, and were less public about their sexual or
      gender minority identity than nonusers. VHA users and nonusers did not differ on
      depression, anxiety, alcohol use, or tobacco use; although VHA users had more
      physical limitations and chronic medical conditions and lower health literacy
      than nonusers. Most lesbian, gay, and transgender VHA users felt welcome at their
      facility and comfortable disclosing their sexual orientation and gender identity
      with their provider. Compared with earlier studies, the positive experiences of
      lesbian, gay, and transgender VHA users in this study provide supportive evidence
      that VHA staff training efforts to raise awareness and competency have been
      successful. Additional efforts are needed to understand why transgender men feel
      less welcome and comfortable disclosing their gender identity. (PsycINFO Database
      Record

PMID- 29369657
TI  - Facial expression predictions as drivers of social perception.
AB  - Emerging perspectives in neuroscience indicate that the brain functions
      predictively, constantly anticipating sensory input based on past experience.
      According to these perspectives, prediction signals impact perception, guiding
      and constraining experience. In a series of six behavioral experiments, we show
      that predictions about facial expressions drive social perception, deeply
      influencing how others are evaluated: individuals are judged as more likable and
      trustworthy when their facial expressions are anticipated, even in the absence of
      any conscious changes in felt affect. Moreover, the effect of predictions on
      social judgments extends to both real-world situations where such judgments have
      particularly high consequence (i.e., evaluating presidential candidates for an
      upcoming election), as well as to more basic perceptual processes that may
      underlie judgment (i.e., facilitated visual processing of expected expressions).
      The implications of these findings, including relevance for cross-cultural
      interactions, social stereotypes and mental illness, are discussed. (PsycINFO
      Database Record

PMID- 29369659
TI  - Behavioral Health Programs in Fire Service: Surveying Access and Preferences.
AB  - Due to the stressful nature of the job, firefighters are likely to be at
      increased risk for behavioral health problems. This study examined the access,
      attitudes, and preferences of a large sample of professional firefighters (N =
      2,156) toward behavioral health services using an online survey. Overall, 81% of
      participants reported that they had access to behavioral health services through
      their fire service department, although smaller departments were less likely to
      offer such services. Despite available programs within fire service, firefighters
      most commonly reported that they would seek outside help from their spouse/family
      (67%) or private professional services (60%). Firefighters with fewer years in
      service were more likely to go to a spouse/family member, coworker, or officer
      for help, whereas those with more years were more likely to seek private
      professional services. Few firefighters directly stated that stigma would prevent
      them from using behavioral health services, yet a large percentage of
      firefighters (68%) reported that they would not recommend these services to
      colleagues, and stigma-related barriers were still among the most significant
      reported. "Clinicians who understand firefighter work culture" was rated as one
      of the most important components to a successful behavioral health program; a
      lack thereof rated as one of the most significant barriers. Offered together,
      these findings suggest that greater exploration of stigma in fire service is
      warranted, and attention toward training culturally competent clinicians to work
      with firefighters is needed. (PsycINFO Database Record

PMID- 29369660
TI  - Posttraumatic Stress Disorder and Interpersonal Process in Homeless Veterans
      Participating in a Peer Mentoring Intervention: Associations With Program
      Benefit.
AB  - Homelessness among veterans has dropped dramatically since the expansion of
      services for homeless veterans in 2009, and now engaging homeless veterans in
      existing programs will be important to continuing to make progress. While one
      promising approach for engaging homeless veterans in care is involving peer
      mentors in integrated services, posttraumatic stress disorder (PTSD) may diminish
      the effects of peer mentorship. This mixed methods study examined how
      interpersonal and emotional processes in homeless veterans with and without PTSD
      impacted their capacity to engage in relationships with peer mentors. Four focus
      groups of 5-8 homeless male veterans (N = 22) were drawn from a larger multisite
      randomized trial. Qualitative analysis identified five primary themes:
      disconnectedness; anger, hostility, or resentment; connecting with others;
      positive view of self; and feeling like an outsider. Thematic comparisons between
      participants with and without a self-reported PTSD diagnosis, and between those
      who did and did not benefit from the peer mentor program, were validated by using
      quantitative methods. Disconnectedness was associated with self-reported PTSD
      diagnosis and with lack of program benefit; feeling like an outsider was
      associated with program benefit. Results suggest that disruption to the capacity
      to develop and maintain social bonds in PTSD may interfere with the capacity to
      benefit from peer mentorship. Social rules and basic strategies for navigating
      interpersonal relationships may differ somewhat within the homeless community and
      outside of it; for veterans who feel disconnected from the domiciled community, a
      formerly homeless veteran peer may serve as a critical "bridge" between the two
      social worlds. (PsycINFO Database Record

PMID- 29369661
TI  - Progressive taxation, income inequality, and happiness.
AB  - Income inequality has become one of the more widely debated social issues today.
      The current article explores the role of progressive taxation in income
      inequality and happiness. Using historical data in the United States from 1962 to
      2014, we found that income inequality was substantially smaller in years when the
      income tax was more progressive (i.e., a higher tax rate for higher income
      brackets), even when controlling for variables like stock market performance and
      unemployment rate. Time lag analyses further showed that higher progressive
      taxation predicted increasingly lower income inequality up to 5 years later. Data
      from the General Social Survey (1972-2014; N = 59,599) with U.S. residents
      (hereafter referred to as "Americans") showed that during years with higher
      progressive taxation rates, less wealthy Americans-those in the lowest 40% of the
      income distribution-tended to be happier, whereas the richest 20% were not
      significantly less happy. Mediational analyses confirmed that the association of
      progressive taxation with the happiness of less wealthy Americans can be
      explained by lower income inequality in years with higher progressive taxation. A
      separate sample of Americans polled online (N = 373) correctly predicted the
      positive association between progressive taxation and the happiness of poorer
      Americans but incorrectly expected a strong negative association between
      progressive taxation and the happiness of richer Americans. (PsycINFO Database
      Record

PMID- 29369662
TI  - On the potential for iatrogenic effects of psychiatric crisis services: The
      example of dialectical behavior therapy for adult women with borderline
      personality disorder.
AB  - OBJECTIVE: Although previous research has suggested that people with a history of
      using psychiatric crisis services are at higher risk for suicide, it is unclear
      whether this link is attributable to individual risk factors or iatrogenic
      effects of service utilization. We examined this question by analyzing data from
      a randomized controlled trial of dialectical behavior therapy (DBT), a treatment
      for highly suicidal individuals in which patients took advantage of crisis
      services less than those in the comparison condition. We hypothesized that crisis
      service utilization during a treatment year, rather than pretreatment indicators
      of suicide risk, would be associated with higher suicide risk after treatment,
      and that DBT's treatment effects would be partially attributable to this
      association. METHOD: Participants were 101 women (Mage = 29.3, 87% Caucasian)
      with recent suicidal and self-injurious behaviors meeting Diagnostic and
      Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric
      Association [APA], 1994) criteria for borderline personality disorder. We
      examined relationships between suicidal ideation (using the Suicide Behaviors
      Questionnaire; Linehan, 1981), number of suicide attempts (using the Suicide
      Attempt Self-Injury Interview; Linehan, Comtois, Brown, Heard, & Wagner, 2006),
      and number of psychiatric inpatient admissions and psychiatric emergency-room
      (ER) visits (using the Treatment History Interview; Linehan & Heard, 1987) from
      the years prior to, during, and following treatment. RESULTS: Treatment-year
      psychiatric ER visits were the sole predictor of the number of follow-up year
      suicide attempts. Treatment condition and pretreatment inpatient admissions
      predicted treatment-year psychiatric ER visits. Finally, there was evidence that
      DBT resulted in fewer suicide attempts at follow-up, in part because getting DBT
      led to fewer psychiatric ER visits. CONCLUSION: In this population and context,
      data suggest that crisis-service utilization conveys risk for suicide. DBT may
      reduce suicide risk in part by reducing use of these services. (PsycINFO Database
      Record

PMID- 29369663
TI  - Preliminary efficacy of service dogs as a complementary treatment for
      posttraumatic stress disorder in military members and veterans.
AB  - OBJECTIVE: Psychiatric service dogs are an emerging complementary treatment for
      military members and veterans with posttraumatic stress disorder (PTSD). Yet
      despite anecdotal accounts of their value, there is a lack of empirical research
      on their efficacy. The current proof-of-concept study assessed the effects of
      this practice. METHOD: A nonrandomized efficacy trial was conducted with 141 post
      9/11 military members and veterans with PTSD to compare usual care alone (n = 66)
      with usual care plus a trained service dog (n = 75). The primary outcome was
      longitudinal change on The PTSD Checklist (PCL; Weathers, Litz, Herman, Huska, &
      Keane, 1993), including data points from a cross-sectional assessment and a
      longitudinal record review. Secondary outcomes included cross-sectional
      differences in depression, quality of life, and social and work functioning.
      RESULTS: Mixed-model analyses revealed clinically significant reductions in PTSD
      symptoms from baseline following the receipt of a service dog, but not while
      receiving usual care alone. Though clinically meaningful, average reductions were
      not below the diagnostic cutoff on the PCL. Regression analyses revealed
      significant differences with medium to large effect sizes among those with
      service dogs compared with those on the waitlist, including lower depression,
      higher quality of life, and higher social functioning. There were no differences
      in employment status, but there was lower absenteeism because of health among
      those who were employed. CONCLUSION: The addition of trained service dogs to
      usual care may confer clinically meaningful improvements in PTSD symptomology for
      military members and veterans with PTSD, though it does not appear to be
      associated with a loss of diagnosis. (PsycINFO Database Record

PMID- 29369664
TI  - Follow-up of monotherapy remitters in the PReDICT study: Maintenance treatment
      outcomes and clinical predictors of recurrence.
AB  - OBJECTIVE: This study followed remitted patients from a randomized controlled
      trial of adults with major depressive disorder (MDD). The aims were to describe
      rates of recurrence and to evaluate 3 clinical predictor domains. METHOD: Ninety
      four treatment-naive patients (50% female; Mage = 38.1 years; 48.9% White; 30.9%
      Hispanic) with MDD who had remitted to 12-week monotherapy (escitalopram,
      duloxetine, or cognitive behavior therapy [CBT]) participated in a 21-month
      maintenance phase (i.e., continued medication or 3 possible CBT booster sessions
      per year). Recurrence was assessed quarterly, and the clinical predictors were
      the following: 2 measures of residual depressive symptoms, 1 measure of lifetime
      depressive episodes, and 2 measures of baseline anxiety. Survival analysis models
      evaluated recurrence rates, and regression models evaluated the predictors.
      RESULTS: Among all patients, 15.5% experienced a recurrence, and the survival
      distributions did not statistically differ among treatments. Residual depressive
      symptoms on the Hamilton Depression Rating Scale at the end of monotherapy were
      associated with increased risk for recurrence (hazard ratio = 1.31, 95%
      confidence interval [CI: 1.02, 1.67], Wald chi2 = 4.41, p = .036), and not having
      a comorbid anxiety disorder diagnosis at study baseline reduced the risk of
      recurrence (hazard ratio = .31, 95% CI [.10, .94], Wald chi2 = 4.28, p = .039).
      CONCLUSIONS: The study supported the benefits of maintenance treatment for
      treatment-naive patients who remitted to initial monotherapy; nevertheless,
      remitted patients with a comorbid anxiety disorder diagnosis at the beginning of
      treatment or residual depressive symptoms after initial treatment were at risk
      for poorer long-term outcomes. (PsycINFO Database Record

PMID- 29369666
TI  - Dynamic longitudinal relations between binge eating symptoms and severity and
      style of interpersonal problems.
AB  - Despite wide recognition of the importance of interpersonal problems in binge
      eating disorder (BED), the nature of this association remains unclear. Examining
      the direction of this longitudinal relationship is necessary to clarify the role
      that interpersonal problems play in the course of binge eating problems, and thus
      to specify treatment targets and mechanisms. This study aimed to articulate the
      bidirectional, longitudinal associations between BED and both the general
      severity of interpersonal problems as well as warm and dominant interpersonal
      styles. Severity and styles of interpersonal problems and BED symptoms were
      measured at baseline, 12 weeks, 24 weeks, and 36 weeks in a sample of 107 women
      in treatment for BED. Results from bivariate latent change score models indicated
      that interpersonal problem severity and BED symptoms are associated
      longitudinally but do not directly influence each other. The results indicated a
      bidirectional interrelation between binge eating symptoms and dominance such that
      less dominance predicted greater decreases in binge eating problems, and less
      binge eating symptoms predicted greater increases in dominance. We also found
      that binge eating symptoms positively predicted changes in warmth (i.e., less
      binge eating symptoms predicted less increases or more decreases in warmth).
      These findings highlight the importance of using dynamic models to examine
      directionality and delineate the distinct roles of interpersonal severity and
      styles in BED trajectories. (PsycINFO Database Record

PMID- 29369665
TI  - Distress intolerance modulation of neurophysiological markers of cognitive
      control during a complex go/no-go task.
AB  - Distress intolerance (DI), a trait-like individual difference reflective of the
      inability to endure aversive affective states, is relevant to multiple forms of
      psychopathology, but its relations to theoretically relevant neurobiological
      systems have received little attention. Altered cognitive control-related
      neurobiology has been theorized to underlie individual differences in DI, but
      little empirical work has been conducted. To test this hypothesis, baseline data
      from a large community sample with elevated high levels of emotional
      psychopathology and comorbidity was utilized (N = 256). Participants completed a
      complex go/no-go task while EEG was recorded, and P2, N2, and P3 amplitudes were
      measured. Based upon prior findings on the relations between these components and
      response inhibition, a core cognitive control function, we hypothesized that DI
      would predict reduced no-go N2 and P3 amplitude while controlling for current
      anxious/depressive symptom severity (i.e., negative affect). Peak amplitudes from
      the raw data and principal components analysis were used to quantify amplitude of
      ERP components. Partially consistent with predictions, high DI was independently
      associated with reduced no-go N2 peak amplitude in the raw ERP data, and was
      significantly related to a frontal positivity factor in the N2 time window across
      no-go and go trials. Contrary to predictions, no relations between DI and the P3
      were found. Overall, results support the theorized relevance of cognitive control
      linked neurobiology to individual differences in tolerance of distress over and
      above distress severity itself, and suggest specific relations between DI and
      alterations in early controlled attention/conflict-monitoring but not response
      inhibition or response inhibition-related sequelae. (PsycINFO Database Record

PMID- 29369667
TI  - Psychopathic traits are associated with reduced fixations to the eye region of
      fearful faces.
AB  - Impairments in processing fearful faces have been documented in both children and
      adults with psychopathic traits, suggesting a potential mechanism by which
      psychopathic individuals develop callous and manipulative interpersonal and
      affective traits. Recently, research has demonstrated that psychopathic traits
      are associated with reduced fixations to the eye regions of faces in samples of
      children and community-dwelling adults, however this relationship has not yet
      been established in an offender sample with high levels of psychopathy. In the
      current study, we employed eye-tracking with paradigms involving the
      identification and passive viewing of facial expressions of emotion,
      respectively, in a sample of adult male criminal offenders (n = 108) to elucidate
      the relationship between visual processing of fearful facial expressions and
      interpersonal and affective psychopathic traits. We found that the interpersonal
      affective traits of psychopathy were significantly related to fewer fixations to
      the eyes of fear faces during the emotion recognition task. This association was
      driven particularly by the interpersonal psychopathic traits (e.g.,
      egocentricity, deceitfulness), whereas fear recognition accuracy was inversely
      related to the affective psychopathic traits (e.g., callousness, lack of
      empathy). These findings highlight potential mechanisms for the subset of the
      interpersonal-affective traits exhibited by psychopathic individuals. (PsycINFO
      Database Record

PMID- 29369669
TI  - Social motivation in schizophrenia: The impact of oxytocin on vigor in the
      context of social and nonsocial reinforcement.
AB  - Experiential negative symptoms-including diminished motivation-have a profound
      impact on functional outcomes in schizophrenia. Animal research suggests that
      abnormalities in dopaminergic regulation can negatively impact effort exertion, a
      translational model that has been applied to individuals with schizophrenia.
      Paradigms that assess effort-based decision making, for example, suggest less
      likelihood of choosing high effort tasks that are high in probability of success,
      and this preference varies with negative symptoms and impaired functioning.
      Although asociality is another well-documented component of experiential negative
      symptoms, it is unclear whether diminished motivation for monetary reward extends
      to the social domain. To test this question, the authors designed the Social
      Vigor Task (SVT)-a measure of effort exertion in the context of live social
      encouragement. They further examined the effect of oxytocin, a neuropeptide
      implicated in social behavior, on vigor. Forty-two individuals with schizophrenia
      and 43 healthy controls completed the SVT twice: once after intranasal
      administration of saline placebo and again after oxytocin. Both groups showed
      similar increases in vigor in response to social encouragement, suggesting effort
      in the social context is spared in schizophrenia. Group differences in the effect
      of social encouragement on vigor varied by point-based reward rate and trial
      length. Oxytocin did not increase vigor during social encouragement in either
      group. Within the schizophrenia group, clinician-rated passive social withdrawal,
      but not active social avoidance, was negatively associated with vigor. Results
      suggest that people with schizophrenia show normative levels of effort in the
      context of social encouragement; low approach motivation, however, relates to
      lower effort. (PsycINFO Database Record

PMID- 29369668
TI  - Are there sex differences in the etiology of youth antisocial behavior?
AB  - Sex differences in the etiology of youth antisocial behavior are an intuitively
      appealing hypothesis given the consistently higher prevalence of antisocial
      behavior in boys versus girls. Although a few early studies supported this
      possibility, reporting stronger genetic influences in females and stronger
      environmental influences in males, subsequent meta-analyses found that antisocial
      behavior was equally heritable in males and females. Critically however, none of
      the meta-analyses evaluated whether sex differences in etiology might be enhanced
      in particular subpopulations or contexts. The current study sought to do just
      this. We examined 1,030 child twin pairs from the Michigan State University Twin
      Registry, half of whom were oversampled for neighborhood disadvantage, thereby
      allowing us to meaningfully evaluate whether sex differences in etiology were
      enhanced in disadvantaged contexts. We also directly evaluated the possibility of
      sex differences in the etiology of teacher- versus maternal-informant reports of
      antisocial behavior, evaluating each informant-report for possible sex
      differences. Results were not consistent with differential effects of sex on
      etiology in disadvantaged versus advantaged contexts, but did suggest moderation
      by informant-report. Namely, genetic influences were stronger in girls, and
      environmental influences were stronger in boys, when antisocial behavior was
      assessed using teacher informant-reports, but not when assessed using maternal
      informant-reports. Critically, these findings were confirmed when we reanalyzed
      meta-analytic data from Burt (2009a) separately by informant. Such findings
      suggest that, at least in school contexts, the etiology of antisocial behavior
      does indeed vary across sex. Implications are discussed. (PsycINFO Database
      Record

PMID- 29369670
TI  - Atypical neural responding to hearing one's own name in adults with ASD.
AB  - Diminished responding to hearing one's own name is one of the earliest and
      strongest predictors of autism spectrum disorder (ASD). Here, we studied, for the
      first time, the neural correlates of hearing one's own name in ASD. Based on
      existing research, we hypothesized enhancement of late parietal positive activity
      specifically for the own name in neurotypicals, and for this effect to be reduced
      in adults with ASD. Source localization analyses were conducted to estimate group
      differences in brain regions underlying this effect. Twenty-one adults with ASD,
      and 21 age- and gender-matched neurotypicals were presented with 3 categories of
      names (own name, close other, unknown other) as task-irrelevant deviant stimuli
      in an auditory oddball paradigm while electroencephalogram was recorded. As
      expected, late parietal positivity was observed specifically for own names in
      neurotypicals, indicating enhanced attention to the own name. This preferential
      effect was absent in the ASD group. This group difference was associated with
      diminished activation in the right temporoparietal junction (rTPJ) in adults with
      ASD. Further, a familiarity effect was found for N1 amplitude, with larger
      amplitudes for familiar names (own name and close other). However, groups did not
      differ for this effect. These findings provide evidence of atypical neural
      responding to hearing one's own name in adults with ASD, suggesting a deficit in
      self-other distinction associated with rTPJ dysfunction. (PsycINFO Database
      Record

PMID- 29369671
TI  - Three approaches to quantifying cigarette consumption: Data from nondaily
      smokers.
AB  - Quantifying cigarette consumption is fundamental to smoking research. We examine
      the correspondence among 3 methods of capturing cigarette consumption in nondaily
      smokers. In the study, 232 nondaily smokers recorded cigarette consumption over 2
      weeks of ad libitum smoking (total = 3,303 days) using 3 methods: (a) interactive
      voice response (IVR; calling an automated telephone line when they smoked), (b)
      butts (storing and returning the butts of cigarettes smoked), and (c) time-line
      follow-back (TLFB; retrospectively reporting daily consumption). Analyses
      examined relationships among the measures (cigarettes per day and proportion of
      days abstinent) for the average over 2 weeks and for each day. In averaged data,
      the methods were highly correlated for both quantity smoked and percentage of
      abstinent days (rs > .95); the average was very reliable (alpha = .99). All 3
      methods showed similar, very strong relationships to urinary cotinine (rs > .70).
      Estimates of the percentage of days abstinent differed modestly but significantly
      by method (butts [32%] > TLFB [31%] > IVR [28%]). For individual days, there was
      no significant difference in cigarettes per day by method, the 3 methods
      correlated highly (rs = .75-.96), and agreement on abstinence was very high
      (>=90%; kappas >= .95). In nondaily smokers reporting smoking by IVR, butts, and
      TLFB, the resulting estimates of cigarette consumption and abstinence are highly
      concordant and equivalent. The composite (average) of the 3 methods yields a
      highly reliable estimate of cigarette-smoking behavior in this population. In
      contrast to past studies, this study suggests these 3 methods are equivalent and
      implies that any 1 can be used by nondaily smokers. (PsycINFO Database Record

PMID- 29369672
TI  - Testing variability in response to a brief alcohol intervention: The role of self
      regulation and the therapeutic relationship.
AB  - The current study tests individual differences in response to a mandated brief
      motivational intervention (BMI) for college student drinking. Participants
      consisted of 99 (45% female) students who were referred for violating campus
      alcohol policy. Within-subject analyses suggest that the BMI led to a significant
      reduction in frequency of drinking and alcohol-related problems at the 1-month
      follow-up, with a nonsignificant trend in reduction of quantity of drinking and
      no difference in maximum level of drinking. However, there was a statistically
      significant amount of variability in response to the BMI across frequency,
      quantity, maximum, and alcohol-related problems. Individual differences in self
      regulation and the strength of the therapeutic relationship were used to predict
      variability in change associated with participating in the intervention. Lower
      levels of self-regulation predicted more alcohol-related problems at 1 month
      following the BMI. A stronger therapeutic relationship predicted lower frequency,
      quantity, and maximum level of drinking at 1 month following the BMI. At the 12
      month follow-up, there was a significant decay in the efficacy of the
      intervention, with a statistically significant amount of variability across all
      outcomes. Lower self-regulation was associated with more problems at 12 months.
      Individual differences in the therapeutic relationship were not associated with
      decay of efficacy between 1 and 12 months across any of the outcome variables.
      Results are consistent with both etiological heterogeneity and common factors
      models of the efficacy of psychotherapy, and extend these models to explaining
      outcomes of brief alcohol interventions in students mandated to treatment.
      (PsycINFO Database Record

PMID- 29369674
TI  - Drinking to cope moderates the efficacy of changing veteran drinking norms as a
      strategy for reducing drinking and alcohol-related problems among U.S. veterans.
AB  - Heavy and problematic drinking is a concern among young adult military veterans.
      Personalized normative feedback (PNF) interventions that target normative
      misperceptions regarding drinking have been efficacious among young adults and
      have recently begun to be implemented among veteran populations in an effort to
      reduce heavy drinking. However, moderators of PNF intervention efficacy among
      veterans are largely unexplored. This study is a secondary data analysis that
      evaluated whether a PNF intervention would work better at reducing perceived
      norms, drinking, and alcohol-related problems specifically for young adult
      veterans who drink to cope with negative affect. Veterans of the United States
      (U.S.) military (86% male; Mean age = 28.9 years, SD = 3.4) were randomly
      assigned to receive either: 1) PNF comparing their drinking and perceived norms
      to actual drinking rates for same sex veterans; or 2) feedback about same sex
      veteran video game play (control condition). Seven hundred eighty-four
      individuals completed baseline and 622 completed 1-month follow-up assessments
      (79% follow-up), including measures of alcohol use, alcohol-related problems, and
      drinking motives. Moderated mediation analyses indicated that changes in
      normative misperceptions as a result of the intervention were more strongly
      associated with reductions in drinking and problems among veterans scoring higher
      on drinking to cope. These findings suggest that PNF may be an especially
      efficacious brief intervention for veterans who drink for coping reasons.
      (PsycINFO Database Record

PMID- 29369673
TI  - A text message intervention to reduce 21st birthday alcohol consumption:
      Evaluation of a two-group randomized controlled trial.
AB  - Twenty-first birthdays are associated with extreme levels of heavy drinking and
      alcohol-related harm. Effective preventive interventions that are acceptable to
      young adults are needed. The current study tested the efficacy of a brief text
      message intervention for reducing 21st birthday alcohol involvement designed to
      correct perceived 21st birthday drinking norms and provide protective behavioral
      strategies (PBS). We also examined potential moderators and mediators. College
      students (n = 200) with an upcoming 21st birthday completed a baseline assessment
      and were randomized to a text-message intervention or an assessment-only control
      condition. For participants in the intervention group, Message 1 (sent one day
      before the birthday celebration) focused on personalized normative feedback, and
      Message 2 (sent day of the birthday celebration) discussed PBS to minimize risk.
      Primary outcomes were assessed using responses to a follow-up assessment the day
      after their birthday celebration (93% completion rate). Zero-inflated negative
      binomial regression analyses did not reveal an overall intervention effect for
      estimated Blood Alcohol Content (eBAC) or alcohol problems on the 21st birthday
      celebration. In partial support of our hypothesis, there was an indirect effect
      of perceived 21st birthday norms on 21st birthday eBAC. The intervention was
      associated with reduced perceived norms, which was, in turn, related to a lower
      eBAC. There was a 3-way interaction between drinks per week, anticipated eBAC,
      and intervention condition for the count portion of actual eBAC such that the
      intervention reduced eBAC among a high-risk subset of the sample. Future research
      may benefit from further refining the personalized normative feedback (PNF)
      component of 21st birthday interventions. (PsycINFO Database Record

PMID- 29369675
TI  - Distance from public transportation and physical activity in Japanese older
      adults: The moderating role of driving status.
AB  - OBJECTIVE: Although previous studies have shown that good access to public
      transportation is positively related with physical activity, the moderators of
      this relationship have not been explored sufficiently in older adults. It is
      possible that driving status could moderate this relationship. The present study
      examined whether the objectively measured distance between public transportation
      and the home was associated with physical activity levels, and whether this
      association was moderated by driving status among Japanese older adults. METHOD:
      In this cross-sectional study, participants (n = 2,878) completed questionnaires
      and wore accelerometers for at least 7 days, to measure their average daily step
      counts and minutes spent engaging in moderate-to-vigorous physical activity. Road
      network distances between the home and the nearest bus stop or train station were
      measured using geographic information systems. Driving status was assessed using
      questionnaires. RESULTS: Multiple regression analyses stratified by driving
      status revealed that, among nondrivers, living further away from public
      transportation was associated with higher step counts (beta = 0.08, p < .001) and
      moderate-to-vigorous physical activity (beta = 0.06, p = .029). Among drivers,
      living closer to public transportation was significantly associated with higher
      moderate-to-vigorous physical activity levels (beta = -0.05, p = .042).
      CONCLUSION: Despite the small effect sizes, the direction of the association
      between distance from public transportation and physical activity was different
      for current drivers and nondrivers. These findings imply that good access to
      public transportation does not positively relate with greater engagement in
      physical activity among nondriving older adults. Shorter distances to public
      transportation might reduce opportunities for engaging in physical activity for
      them. (PsycINFO Database Record

PMID- 29369676
TI  - Lifetime trauma, perceived control, and all-cause mortality: Results from the
      Midlife in the United States Study.
AB  - OBJECTIVE: To investigate whether lifetime-trauma exposure predicts all-cause
      mortality and whether this association is mediated or moderated by perceived
      control. METHOD: A sample of middle-aged and older adults (N = 4,961) who
      participated in the second wave of the Midlife in the United States Study (MIDUS)
      provided data. Lifetime trauma was operationalized using the reported number of
      potentially traumatic experiences spanning childhood through adulthood. Both the
      perceived constraints and mastery dimensions of perceived control were examined.
      Cox regression models tested main effects and interactions of lifetime trauma
      with mastery and constraints predicting 10-year mortality risk. RESULTS: There
      was a significant main effect of lifetime trauma, b = .06, hazard ratio (HR) =
      1.07, p = .032, and an interaction of trauma with mastery, b = -.08, p = .004. A
      greater number of traumatic experiences was associated with increased mortality
      risk at below-average levels of mastery, -1 SD; HR = 1.14, p < .001, but not at
      above-average levels, +1 SD; HR = 0.97, p = .48. This interaction persisted after
      further adjustment for health status, psychological, and behavioral covariates.
      An association of constraints with elevated mortality risk, HR = 1.33, p = .008,
      was attenuated in a fully adjusted model, HR = 1.06, p = .26. CONCLUSION: A
      strong sense of mastery may buffer elevated mortality risk associated with
      exposure to traumatic experiences. Findings extend evidence that mastery may
      foster resilience to the adverse health effects of traumatic stressors, whereas
      constraints may show stronger independent associations with health outcomes.
      (PsycINFO Database Record

PMID- 29369677
TI  - A prospective study of marital quality and body weight in midlife.
AB  - OBJECTIVE: Few studies have gone beyond studying marital status to examine
      effects of marital quality on body weight. This study examined the association of
      marital quality with weight change and incident obesity in midlife. It
      differentiated positive and negative components of marital quality considering
      overall marital quality, marital support, and marital strain. METHOD: Data are
      from 2,636 adults from the Midlife in the United States study who participated in
      2 waves of data collection 10 years apart. Marital quality was self-reported.
      Body weight was assessed with self-reported height and weight. Generalized
      estimating equations examined primary associations also considering potential
      confounders and mediating factors including sociodemographics, baseline health
      conditions, and health behaviors. RESULTS: Overall marital quality was inversely
      associated with weight gain (beta = -0.70, 95% confidence interval [CI] [-1.38, 
      0.01]). Marital support was inversely related to both weight gain (beta = -1.48,
      95% CI [-2.80, -0.16]) and incident obesity (risk ratio = 0.79, 95% CI [0.65,
      0.96]). Marital strain was not associated with either weight change or incident
      obesity. The association between marital support and incident obesity remained
      when marital strain was simultaneously included in the model. There was evidence
      that the associations of marital support and marital strain with incident obesity
      might differ by gender, and were evident only in men. CONCLUSION: This study
      shows a supportive marital relationship is associated with healthier body weight
      in midlife. It also indicates marital support may have effects over and beyond
      the mere absence of marital strain. Findings suggest the potential utility of
      involving spouses/partners in obesity prevention and treatment. (PsycINFO
      Database Record

PMID- 29369678
TI  - Daily meaning salience and physical activity in previously inactive exercise
      initiates.
AB  - OBJECTIVE: Individuals living with more experienced meaning, or meaning salience,
      may be more likely to engage in health behaviors including physical activity.
      This study examined daily meaning salience and physical activity in previously
      inactive exercise initiates. METHOD: Inactive adults (N = 80, 78% female, Mage =
      43 years, SD = 11 years) intending to increase physical activity participated in
      a daily diary study. At baseline, participants completed self-report
      questionnaires of demographics, global meaning and purpose, depressive symptoms,
      and motivation. Fitness center attendance was extracted from the member database.
      Participants self-reported meaning salience, positive mood, negative mood, and
      physical activity (duration in minutes; intensity in ratings of perceived
      exertion) daily for the first 28 days. Multilevel and multiple regression
      analyses were used. RESULTS: Multilevel models revealed that controlling for
      demographics, mood, and motivation, for every standard deviation increase in
      meaning salience, participants were 44% more likely to visit the fitness center,
      odds ratio (OR) = 1.44, 95% CI [1.24,1.68], p < .001. Further, increases in
      meaning salience above average were positively related to physical activity
      duration, beta = .19, p < .001, and intensity, beta = .13, p < .001. Global
      meaning and purpose were not significantly related to physical activity duration,
      physical activity intensity, or fitness center visits over the 28 days.
      CONCLUSIONS: Results suggest that increased meaning salience, but not global
      meaning or purpose, is associated with physical activity participation in
      previously inactive exercise initiates, and may be a proximal predictor of
      physical activity behavior. Future research should use ecological momentary
      assessment (EMA) designs to examine the relationship within days and over longer
      intervals. (PsycINFO Database Record

PMID- 29369679
TI  - A meta-synthesis of studies of patients' experience of living with terminal
      cancer.
AB  - OBJECTIVE: The aim of this research was to produce a synthesis of
      phenomenological studies of the experience of living with the awareness of having
      terminal cancer to gain a more complete understanding of the parameters of this
      experience. METHODS: This research used meta-synthesis as a method for
      integrating the results of 23 phenomenological studies of the experience of
      living with the awareness of having terminal cancer published between 2011 and
      2016. RESULTS: The meta-synthesis generated 19 theme clusters that informed the
      construction of four master themes: trauma, liminality, holding on to life, and
      life as a cancer patient. Each master theme captures a distinct experiential
      dimension of living with the awareness of having terminal cancer. Each dimension
      brings with it significant and distinctive psychological challenges. CONCLUSION:
      The results from the present meta-synthesis suggest that the experience of living
      with the awareness of having terminal cancer is a multidimensional experience
      that patients actively negotiate as they search for ways in which they can rise
      to the psychological challenges associated with it. A better understanding of the
      parameters of this experience can help health care professionals provide
      appropriate support for this client group. (PsycINFO Database Record

PMID- 29369680
TI  - Prospect theory reflects selective allocation of attention.
AB  - There is a disconnect in the literature between analyses of risky choice based on
      cumulative prospect theory (CPT) and work on predecisional information
      processing. One likely reason is that for expectation models (e.g., CPT), it is
      often assumed that people behaved only as if they conducted the computations
      leading to the predicted choice and that the models are thus mute regarding
      information processing. We suggest that key psychological constructs in CPT, such
      as loss aversion and outcome and probability sensitivity, can be interpreted in
      terms of attention allocation. In two experiments, we tested hypotheses about
      specific links between CPT parameters and attentional regularities. Experiment 1
      used process tracing to monitor participants' predecisional attention allocation
      to outcome and probability information. As hypothesized, individual differences
      in CPT's loss-aversion, outcome-sensitivity, and probability-sensitivity
      parameters (estimated from participants' choices) were systematically associated
      with individual differences in attention allocation to outcome and probability
      information. For instance, loss aversion was associated with the relative
      attention allocated to loss and gain outcomes, and a more strongly curved
      weighting function was associated with less attention allocated to probabilities.
      Experiment 2 manipulated participants' attention to losses or gains, causing
      systematic differences in CPT's loss-aversion parameter. This result indicates
      that attention allocation can to some extent cause choice regularities that are
      captured by CPT. Our findings demonstrate an as-if model's capacity to reflect
      characteristics of information processing. We suggest that the observed CPT
      attention links can be harnessed to inform the development of process models of
      risky choice. (PsycINFO Database Record

PMID- 29369681
TI  - The importance of awareness for understanding language.
AB  - Is consciousness required for high level cognitive processes, or can the
      unconscious mind perform tasks that are as complex and difficult as, for example,
      understanding a sentence? Recent work has argued that, yes, the unconscious mind
      can: Sklar et al. (2012) found that sentences, masked from consciousness using
      the technique of continuous flash suppression (CFS), broke into awareness more
      rapidly when their meanings were more unusual or more emotionally negative, even
      though processing the sentences' meaning required unconsciously combining each
      word's meaning. This has motivated the important claim that consciousness plays
      little-to-no functional role in high-level cognitive operations. Here, we aimed
      to replicate and extend these findings, but instead, across 10 high-powered
      studies, we found no evidence that the meaning of a phrase or word could be
      understood without awareness. We did, however, consistently find evidence that
      low-level perceptual features, such as sentence length and familiarity of
      alphabet, could be processed unconsciously. Our null findings for sentence
      processing are corroborated by a meta-analysis that aggregates our studies with
      the prior literature. We offer a potential explanation for prior positive results
      through a set of computational simulations, which show how the distributional
      characteristics of this type of CFS data, in particular its skew and heavy tail,
      can cause an elevated level of false positive results when common data exclusion
      criteria are applied. Our findings thus have practical implication for analyzing
      such data. More importantly, they suggest that consciousness may well be required
      for high-level cognitive tasks such as understanding language. (PsycINFO Database
      Record

PMID- 29369682
TI  - Attention goes both ways: Shifting attention influences lexical decisions.
AB  - Spatial components of concepts can influence the speed with which peripheral
      targets are responded to (e.g., the word God speeds responses to targets
      presented above fixation; devil speeds responses to targets presented below
      fixation). The basic premise underlying these conceptual cueing effects is that
      thinking of a spatial metaphor activates an internal spatial representation which
      in turn influences the allocation of attention in the visual field. An important
      step forward in understanding conceptual cues is determining whether the
      underlying process is bidirectional: Do shifts of attention facilitate activation
      of corresponding conceptual information? To test this, a peripheral cue was used
      to induce shifts of attention to a peripheral location, and the effect of this
      shift on concept processing was measured with a standard lexical-decision task in
      which participants made word/nonword responses to a letter string presented at
      fixation (Experiments 1 and 3), or with a modified lexical-decision task in which
      participants made English/Dutch judgments of a word presented auditorily
      (Experiment 2). If shifts of attention activate spatially compatible concepts,
      then shifting attention to a peripheral location should speed lexical decisions
      for spatially compatible concepts such that leftward shifts lead to faster
      lexical decisions of left relative to right concepts (and likewise for rightward,
      upward, and downward shifts). Our results support this prediction, suggesting
      that behaviors in the visual field can influence the activation of internal
      representations. (PsycINFO Database Record

PMID- 29369683
TI  - Tool use changes the spatial extension of the magnetic touch illusion.
AB  - Characterizing the brain mechanisms that allow humans to use tools to interact
      with the environment is a major goal in neuroscience. It has been proposed that
      handheld tools are incorporated into the multisensory representation of the body
      and its surrounding (peripersonal) space, underlying our remarkable tool use
      ability. One single-cell recording study in tool-using monkeys provided
      qualitative support for this hypothesis, and the results from a vast number of
      human studies employing different experimental paradigms have been ambiguous.
      Here, we made use of the recently reported magnetic touch illusion-a perceptual
      correlate of peripersonal space-to examine the effect of tool use on the
      representation of visuotactile peripersonal space. The results showed that active
      tool use leads to an extension of the "illusion volume" around the entire length
      of a tool, which was significantly greater compared with a manual control task.
      These findings support the notion that the multisensory representation of
      peripersonal space is extended to incorporate handheld tools and provide a three
      dimensional estimation of this remapping process. (PsycINFO Database Record

PMID- 29369685
TI  - Characteristics of Two Lysis-Related Proteins from a Shewanella putrefaciens
      Phage with High Lytic Activity and Wide Spectrum.
AB  - Although Shewanella putrefaciens is the specific spoilage organism in most
      seafood, only seven Shewanella phages have been sequenced and their endolysins
      have not been reported until now. In this study, we cloned and expressed two
      lysis-related proteins (Spp64 and Spp62) encoded by phage Spp001, the first
      sequenced S. putrefaciens phage. Both recombinant proteins showed strong lytic
      capability toward chilled S. putrefaciens Sp225 and presented a wider activity
      spectrum compared with bacteriophage Spp001. The enzymatic activity of crude
      Spp64, Spp62DeltaTD, and Spp62DeltaTD-GST can cause decreases of 0.691, 0.674,
      and 0.685, respectively, as tested through the turbidity reduction assay.
      Furthermore, purified enzyme Spp64 at concentrations of 537.5 and 4.20 MUg/mL was
      enough to decrease the optical density of chilled S. putrefaciens by 0.881 and
      0.492, respectively, within 15 min. The recombinant Spp64 has a peptidase
      catalytic domain and exhibits high temperature resistance. Moreover, Spp64
      displayed superior enzymatic activity in a range of pH values that matches
      environmental conditions (pH between 5.0 and 10.0), which demonstrates that its
      application in seafood is feasible. The present work is to our knowledge the
      first report on lysis-related enzymes encoded in the Shewanella phage. Both
      proteins presented extraordinary potential to control S. putrefaciens; we hope
      that these proteins can be developed as novel antibacterial agents in further
      research.

PMID- 29369684
TI  - Respiratory Symptoms in Young Adults and Future Lung Disease. The CARDIA Lung
      Study.
AB  - RATIONALE: There are limited data on factors in young adulthood that predict
      future lung disease. OBJECTIVES: To determine the relationship between
      respiratory symptoms, loss of lung health, and incident respiratory disease in a
      population-based study of young adults. METHODS: We examined prospective data
      from 2,749 participants in the CARDIA (Coronary Artery Risk Development in Young
      Adults) study who completed respiratory symptom questionnaires at baseline and 2
      years later and repeated spirometry measurements over 30 years. MEASUREMENTS AND
      MAIN RESULTS: Cough or phlegm, episodes of bronchitis, wheeze, shortness of
      breath, and chest illnesses at both baseline and Year 2 were the main predictor
      variables in models assessing decline in FEV1 and FVC from Year 5 to Year 30,
      incident obstructive and restrictive lung physiology, and visual emphysema on
      thoracic computed tomography scan. After adjustment for covariates, including
      body mass index, asthma, and smoking, report of any symptom was associated with 
      2.71 ml/yr excess decline in FEV1 (P < 0.001) and -2.18 in FVC (P < 0.001) as
      well as greater odds of incident (prebronchodilator) obstructive (odds ratio
      [OR], 1.63; 95% confidence interval [CI], 1.24-2.14) and restrictive (OR, 1.40;
      95% CI, 1.09-1.80) physiology. Cough-related symptoms (OR, 1.56; 95% CI, 1.13
      2.16) were associated with greater odds of future emphysema. CONCLUSIONS:
      Persistent respiratory symptoms in young adults are associated with accelerated
      decline in lung function, incident obstructive and restrictive physiology, and
      greater odds of future radiographic emphysema.

PMID- 29369686
TI  - Heavy Metals in Spring and Bottled Drinking Waters of Sibylline Mountains
      National Park (Central Italy).
AB  - Heavy metal concentrations (cadmium, lead, and copper) in spring, tap, and
      bottled waters of the Sibylline Mountains National Park (central Italy) were
      investigated using square wave anodic stripping voltammetry from 2004 to 2011.
      The mean (+/-SD) concentrations detected (1.3 +/- 0.4 ng L-1 cadmium, 14 +/- 6 ng
      L-1 lead, and 0.16 +/- 0.10 MUg L-1 copper) were below the limits stipulated by
      Italian and European legislation for drinking and natural mineral water. In the
      three studied areas of the park (Mount Bove north, Mount Bove south, and springs
      of River Nera) with very few exceptions, both mineral waters bottled in the area
      and aqueduct waters from public fountains had approximately the same metal
      concentrations as did the spring waters from which they were derived. Conversely,
      substantially higher metal concentrations were found at some sites in private
      houses, which may be due to release of metals from old metal pipes. At the time
      of this study, waters of Sibylline Mountains National Park were of good quality,
      and no influence of the bottling process on heavy metal concentrations was found.

PMID- 29369687
TI  - A Limited Survey of Heavy Metal Concentrations in Fresh and Frozen Cuttlefish Ink
      and Mantle Used As Food.
AB  - Cuttlefish ink is consumed as a delicacy worldwide. The current study is the
      first assessment of heavy metal concentrations in cuttlefish ink versus mantle
      under different storage methods. A total of 212 samples (64 of fresh mantle, 42
      of frozen mantle, 64 of fresh ink, and 42 of frozen ink) were analyzed for the
      detection of the following heavy metals: arsenic (As), chromium (Cr), iron (Fe),
      lead (Pb), mercury (Hg), and cadmium (Cd). The median As concentrations were 12.9
      mg/kg for fresh mantle, 8.63 mg/kg for frozen mantle, 10.8 mg/kg for frozen ink,
      and 0.41 mg/kg for fresh ink. The median Cr concentrations were 0.06 mg/kg for
      fresh mantle and frozen ink, 0.03 mg/kg for frozen mantle, and below the limit of
      quantification (LOQ) for fresh ink. The median Fe concentrations were 4.08 mg/kg
      for frozen ink, 1.51 mg/kg for fresh mantle, 0.73 mg/kg for frozen mantle, and
      below the LOQ for fresh ink. The median Pb concentrations of almost all samples
      were below the LOQ; only two frozen ink, one fresh ink, one frozen mantle, and
      one fresh mantle sample exceeded the limit stipulated by the European Union. The
      Hg concentrations were statistically similar among the four categories of
      samples; the median Hg concentrations were below the LOQ, and the maximum
      concentrations were found in frozen ink, at 1.62 mg/kg. The median Cd
      concentrations were 0.69 mg/kg for frozen ink and 0.11 mg/kg for frozen mantle,
      fresh mantle and fresh ink concentrations were below the LOQ, and in 11.3% of the
      tested samples, Cd concentrations were higher than the European Union limit. The
      probability of samples having a Cd concentration above the legal limit was 35.75
      times higher in frozen than in fresh products. Fresh ink had significantly lower
      concentrations of As, Cr, Fe, and Cd, but the concentrations of Hg and Pb were
      not significantly different from those of other products. Frozen ink had
      significantly higher concentrations of Cd, Cr, and Fe, but concentrations of As
      were lower than those in fresh mantle, pointing out a possible role for the
      freezing process and for different fishing zones as risk factors for heavy metal
      contamination.

PMID- 29369688
TI  - Outbreak of Escherichia coli O157:H7 Infections Linked to Aged Raw Milk Gouda
      Cheese, Canada, 2013.
AB  - Between 12 July and 29 September 2013, 29 individuals in five Canadian provinces
      became ill following infection with the same strain of Escherichia coli O157:H7
      as defined by molecular typing results. Five case patients were hospitalized, and
      one died. Twenty-six case patients (90%) reported eating Gouda cheese originating
      from a dairy plant in British Columbia. All of the 22 case patients with
      sufficient product details available reported consuming Gouda cheese made with
      raw milk; this cheese had been produced between March and July 2013 and was aged
      for a minimum of 60 days. The outbreak strain was isolated from the implicated
      Gouda cheese, including one core sample obtained from an intact cheese wheel 83
      days after production. The findings indicate that raw milk was the primary source
      of the E. coli O157:H7, which persisted through production and the minimum 60-day
      aging period. This outbreak is the third caused by E. coli O157:H7 traced to
      Gouda cheese made with raw milk in North America. These findings provide further
      evidence that a 60-day ripening period cannot ensure die-off of pathogens that
      might be present in raw milk Gouda cheese after production and have triggered an
      evaluation of processing conditions, physicochemical parameters, and options to
      mitigate the risk of E. coli O157:H7 infection associated with raw milk Gouda
      cheese produced in Canada.

PMID- 29369689
TI  - Dynamic Predictive Model for Growth of Bacillus cereus from Spores in Cooked
      Beans.
AB  - Kinetic growth data for Bacillus cereus grown from spores were collected in
      cooked beans under several isothermal conditions (10 to 49 degrees C). Samples
      were inoculated with approximately 2 log CFU/g heat-shocked (80 degrees C for 10
      min) spores and stored at isothermal temperatures. B. cereus populations were
      determined at appropriate intervals by plating on mannitol-egg yolk-polymyxin
      agar and incubating at 30 degrees C for 24 h. Data were fitted into Baranyi,
      Huang, modified Gompertz, and three-phase linear primary growth models. All four
      models were fitted to the experimental growth data collected at 13 to 46 degrees
      C. Performances of these models were evaluated based on accuracy and bias
      factors, the coefficient of determination ( R2), and the root mean square error.
      Based on these criteria, the Baranyi model best described the growth data,
      followed by the Huang, modified Gompertz, and three-phase linear models. The
      maximum growth rates of each primary model were fitted as a function of
      temperature using the modified Ratkowsky model. The high R2 values (0.95 to 0.98)
      indicate that the modified Ratkowsky model can be used to describe the effect of
      temperature on the growth rates for all four primary models. The acceptable
      prediction zone (APZ) approach also was used for validation of the model with
      observed data collected during single and two-step dynamic cooling temperature
      protocols. When the predictions using the Baranyi model were compared with the
      observed data using the APZ analysis, all 24 observations for the exponential
      single rate cooling were within the APZ, which was set between -0.5 and 1 log
      CFU/g; 26 of 28 predictions for the two-step cooling profiles also were within
      the APZ limits. The developed dynamic model can be used to predict potential B.
      cereus growth from spores in beans under various temperature conditions or during
      extended chilling of cooked beans.

PMID- 29369690
TI  - Antibiotic Resistance Profile of Commensal Escherichia coli Isolated from Broiler
      Chickens in Qatar.
AB  - Antibiotic resistance (AR) is a growing public health concern worldwide, and it
      is a top health challenge in the 21st century. AR among Enterobacteriaceae is
      rapidly increasing, especially in third-generation cephalosporins and
      carbapenems. Further, strains carrying mobilized colistin resistance ( mcr) genes
      1 and 2 have been isolated from humans, food-producing animals, and the
      environment. The uncontrolled use of antibiotics in food-producing animals is a
      major factor in the generation and spread of AR. No studies have been done to
      evaluate AR in the veterinary sector of Qatar. This study aimed at establishing
      primary baseline data for the prevalence of AR among food-producing animals in
      Qatar. Fecal samples (172) were obtained from two broiler farms and one live bird
      market in Qatar, and 90 commensal Escherichia coli bacteria were isolated and
      subjected to susceptibility testing against 16 clinically relevant antibiotics by
      using the E-test method. The results found that 81 (90%) of 90 isolates were
      resistant to at least one antibiotic, 14 (15.5%) of 90 isolates were colistin
      resistant, 2 (2.2%) of 90 isolates were extended-spectrum beta-lactamase
      producers, and 2 (2.2%) of 90 isolates were multidrug resistant to four
      antibiotic classes. Extended-spectrum beta-lactamase-producing E. coli and
      colistin-resistant isolates were confirmed by using double-disc susceptibility
      testing and PCR, respectively. Such a high prevalence of antibiotic-resistant E.
      coli could be the result of a long application of antibiotic treatment, and it is
      an indicator of the antibiotic load in food-producing animals in Qatar. Pathogens
      carrying AR can be easily transmitted to humans through consumption of
      undercooked food or noncompliance with hygiene practices, mandating prompt
      development and implementation of a stewardship program to control and monitor
      the use of antibiotics in the community and agriculture.

PMID- 29369691
TI  - Accumulation of Polychlorinated Biphenyls in Mussels: A Proteomic Study.
AB  - Polychlorinated biphenyls (PCBs) are environmental pollutants of industrial
      origin that can contaminate food, mainly food of animal origin. Although
      production of PCBs has been banned in many countries since the 1980s, they are
      still present in the environment and are considered dangerous pollutants for
      human health. In fact, they can bioaccumulate in living organisms such as marine
      organisms because of their chemical and physical properties. New analytical
      approaches are useful to monitor the presence of such contaminants in seafood
      products and in the environment. In this work, we evaluate changes in protein
      expression of Mytilus galloprovincialis (Lam.) experimentally exposed to a PCB
      mixture and identify chemically specific protein expression signatures by using a
      proteomic approach. In particular, we identify 21 proteins whose levels of
      expression are sensibly modified after 3 weeks of exposure. The present work
      shows that a proteomic approach can be a useful tool to study alterations of
      protein expression in mussels exposed to PCBs and represents a first step toward
      the development of screening protocols to be used for biomonitoring surveys of
      fishery products.

PMID- 29369692
TI  - Treating Hypertension During Breastfeeding.

PMID- 29369693
TI  - Evaluation of a Method for Long-Term Cryopreservation of Fungal Strains.
AB  - The conservation of microorganisms is essential for their in-depth study.
      However, today's most widely used conservation methods, based on the use of
      distilled water, soil, oils, or silica, do not guarantee the stability of fungal
      cells, especially dermatophytes. This problem led us to evaluate the conservation
      capacity of a cryogenic vials system containing glass beads covered in a
      cryopreservant hypertonic solution as an alternative method of storage of fungal
      cells at -80 degrees C. Up to 570 strains of fungi belonging to 27 different
      species, isolated from clinical samples, were inoculated into cryotubes
      containing 25 glass beads covered in a cryopreserving hypertonic solution.
      Suspensions were mixed vigorously and the cryopreserving solution was discarded.
      The tubes were frozen at -80 degrees C for a period of 42 months and
      periodically, a glass bead was removed from each cryotube and inoculated onto
      Sabouraud dextrose agar, and incubated at 30 degrees C for 7-14 days to evaluate
      the number of colonies recovered, their purity, and phenotypic characteristics.
      All yeast isolates were recovered, unlike 2 isolates (4.4%) of the mold group and
      21 (10.7%) of the dermatophytes. Survival rates were close to 100% for yeasts and
      molds, with expiration times being estimated for almost indefinite stocks, and
      62% for dermatophytes, with an average expiration date of 25.5 years. The
      phenotypic characteristics remained comparable to those of the strains before
      storage. Conservation at -80 degrees C using cryogenic vials is a reliable and
      efficient system for the conservation of fungal collections, and although the
      behavior differs by groups, stratified survival data are obtained to avoid
      extinction.

PMID- 29369695
TI  - Integrin Heterodimers Expressed on the Surface of Porcine Spermatogonial Stem
      Cells.
AB  - To date, in vitro culture systems able to sufficiently expand the small
      population of spermatogonial stem cells (SSCs), a tool for the development of
      sperm-mediated gene transfer techniques in transgenic pigs, in the porcine
      seminiferous tubule have not been reported. Therefore, as a step toward
      engineering a noncellular niche to support the in vitro maintenance of porcine
      SSC self-renewal, we investigated the types of integrin heterodimers that are
      expressed and functional on their membrane. The alpha and beta integrin subunit
      protein expressions were analyzed using immunocytochemistry and fluorescence
      immunoassay, and the function of integrin heterodimers was confirmed by
      attachment and antibody inhibition assays. The integrin subunits, alpha3, alpha4,
      alpha5, alpha6, alpha8, alpha9, alphaV, and beta1, were identified on the surface
      of them. Moreover, they showed significantly increased adhesion to fibronectin,
      laminin, and vitronectin, and functional blocking of integrin alpha4beta1,
      alpha6beta1, or alphaVbeta1 significantly inhibited adhesion to these molecules.
      They showed significantly decreased adhesion to tenascin C and functional
      blocking of integrin alpha5beta1 did not significantly inhibit adhesion to
      fibronectin. Accordingly, we confirmed that the integrin heterodimers
      alpha4beta1, alpha6beta1, and alphaVbeta1 actively function on the surface of
      undifferentiated porcine SSCs, whereas alpha3, alpha5, alpha8, and alpha9 are
      present in inactive forms.

PMID- 29369696
TI  - Disease or adaptation: another look at the practice of medicine.
AB  - The practice of medicine has changed considerably over the past few decades and
      is now focusing more and more on early intervention strategies. As a result, we
      tend to consider pre-symptomatic abnormalities, however small, already as a
      potential target for treatment. In this viewpoint, we argue that we should put
      more emphasis on pathophysiological thinking as many of the so-called early
      abnormalities may, in fact, reflect adaptive mechanisms rather than disease. This
      view should influence medical care and education, emphasizing the importance of
      knowledge of pathophysiology.

PMID- 29369697
TI  - A new era for autism research, and for our journal.

PMID- 29369698
TI  - Through the Glass Ceiling.

PMID- 29369699
TI  - Single Nucleotide Polymorphisms in CD40L Predict Endothelial Complications and
      Mortality After Allogeneic Stem-Cell Transplantation.
AB  - Purpose Endothelial vulnerability is a potential risk factor for complications
      after allogeneic stem-cell transplantation (alloSCT). The CD40/CD40 ligand
      (CD40L) axis contributes to inflammatory diseases and is upregulated in
      endothelial cells upon activation, suggesting a role in alloSCT biology. Here, we
      studied single nucleotide polymorphisms (SNPs) in the CD40L gene in recipients of
      alloSCT. Patients and Methods Three CD40L SNPs (rs3092920, rs3092952, rs3092936)
      were analyzed for association with transplant-associated thrombotic
      microangiopathy, overall nonrelapse mortality (NRM), and NRM after acute graft
      versus-host disease in 294 recipients of alloSCT without statin-based endothelial
      prophylaxis (SEP). The significant genotype was then put into perspective with
      established thrombomodulin ( THBD) gene polymorphisms. Findings were validated in
      an independent cohort without SEP and in an additional 344 patients who received
      SEP. Results The rs3092936 CC/CT genotype was associated with an increased risk
      of transplant-associated thrombotic microangiopathy ( P = .001), overall NRM ( P
      = .03), and NRM after acute graft-versus-host disease ( P = .01). The rs3092936
      CC/CT genotype was largely mutually exclusive of high-risk THBD SNPs. Both CD40L
      and THBD SNPs predicted adverse overall survival (OS) and overall NRM to a
      similar extent in training cohort (OS, P = .04; NRM, P < .001) and validation
      cohort (OS, P = .01; NRM, P = .001) without SEP. In contrast, SEP completely
      abolished the influence of the high-risk CD40L and THBD SNPs ( P = .40).
      Conclusion An increased risk of endothelial complications can be predicted before
      alloSCT by genetic markers in the recipient's genome. The normalization of
      mortality risks in patients treated with SEP suggests a way of overcoming the
      negative effect of high-risk genotypes and warrants further clinical validation.

PMID- 29369700
TI  - Reply to M.F. Chong et al.

PMID- 29369701
TI  - Targeting DNA Repair in Prostate Cancer.

PMID- 29369702
TI  - Thalidomide for Delayed Chemotherapy-Induced Nausea and Vomiting: Where Is Its
      Place in Therapy?

PMID- 29369703
TI  - Recent advances in extracorporeal life support as a bridge to lung
      transplantation.
AB  - INTRODUCTION: Invasive mechanical respiratory support in candidate bridging to
      transplant (BTT) has become common practice in recent years. This usually
      consists of mechanical ventilation, extracorporeal life support (ECLS) or a
      combination of both techniques. Areas covered: This review covers epidemiology,
      technical considerations, indications and outcome of ELCS as BTT. Published
      literature was identified by searching the MEDLINE bibliographic database (1946
      present) and appropriate papers were reviewed. In a retrospective analysis of the
      period 2010-2016 (n = 92 cases of ECLS bridging, 62% ECLS only) at our
      institution, bridging success was 73%, with 1-year survival among patients
      surviving to transplant 78%, surpassing our previously published results between
      2005-2009 (bridging success 58%, 1-year survival 58%, p = 0.002 and p = 0.02,
      respectively). Expert commentary: While ECLS success has influenced lung
      transplant selection criteria, bridging remains technically and ethically
      challenging. Candidate selection and organ allocation are crucial to achieving
      acceptable results.

PMID- 29369704
TI  - Reply to H. Tilly et al.

PMID- 29369705
TI  - Studies on the Influence of Long-Acting Insulin Analogs on Cancer Risk Should Be
      Based on the New-User Design Only.

PMID- 29369706
TI  - Reply to P. Autier et al.

PMID- 29369707
TI  - Ataxia Telangiectasia-Mutated and Rad3-Related Inhibition and Topoisomerase I
      Trapping Create a Synthetic Lethality in Cancer Cells.

PMID- 29369708
TI  - Reduced left atrial myocardial deformation irrespective of cavity size: a
      potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis.
AB  - BACKGROUND: Cardiac amyloidosis (CA) is a myocardial disease and commonly under
      diagnosed condition. In CA patients, atrial fibrillation might occur in the
      absence of left atrial (LA) enlargement. OBJECTIVES: The aim of this study is to
      assess LA size and function, and its relationship with atrial arrhythmia in
      patients with hereditary transthyretin amyloidosis (ATTR). METHODS: Forty-six
      patients with confirmed ATTR amyloidosis on abdominal biopsy were studied.
      Assessment with 2D echocardiography and 2D strain showed 31 patients had
      increased LV wall thickness (LVWT) (septal thickness >12 mm), and 15 had normal
      LVWT. In addition to conventional measurements, LV and LA global longitudinal
      strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done
      to assess fibril type. ATTR patients with increased LVWT were compared with 23
      patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR
      amyloidosis patients also underwent 24 hour Holter monitoring to determine the
      presence of atrial arrhythmia. RESULTS: Atrial deformation during atrial systole
      was reduced in ATTR amyloidosis patients with increased LVWT independent of LA
      size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had
      ECG evidence of significant atrial arrhythmic events. LA strain rate, during
      atrial systole, was the only independent predictor of atrial arrhythmia (beta =
      3.28, p = .012). CONCLUSION: In ATTR cardiomyopathy with increased LVWT, LA
      myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA
      myocardial SR during atrial systole, irrespective of cavity volume, E/e' and LV
      deformation, is also a strong predictor for atrial arrhythmic events.

PMID- 29369709
TI  - Multi-Armed Droplets as Shape-Changing Protocells.
AB  - Protocells are objects that mimic one or several functions of biological cells
      and may be embodied as solid particles, lipid vesicles, or droplets. Our work is
      based on using decanol droplets in an aqueous solution of sodium decanoate in the
      presence of salt. A decanol droplet under such conditions bears many qualitative
      similarities with living cells, such as the ability to move chemotactically,
      divide and fuse, or change its shape. This article focuses on the description of
      a shape-changing process induced by the evaporation of water from the decanoate
      solution. Under these conditions, the droplets perform complex shape changes,
      whereby the originally round decanol droplets grow into branching patterns and
      mimic the growth of appendages in bacteria or axon growth of neuronal cells. We
      report two outcomes: (i) the morphological changes are reversible, and (ii)
      multiple protocells avoid contact between each other during the morphological
      transformation. The importance of these morphological changes in the context of
      artificial life are discussed.

PMID- 29369710
TI  - Undecidability and Irreducibility Conditions for Open-Ended Evolution and
      Emergence.
AB  - Is undecidability a requirement for open-ended evolution (OEE)? Using methods
      derived from algorithmic complexity theory, we propose robust computational
      definitions of open-ended evolution and the adaptability of computable dynamical
      systems. Within this framework, we show that decidability imposes absolute limits
      on the stable growth of complexity in computable dynamical systems. Conversely,
      systems that exhibit (strong) open-ended evolution must be undecidable,
      establishing undecidability as a requirement for such systems. Complexity is
      assessed in terms of three measures: sophistication, coarse sophistication, and
      busy beaver logical depth. These three complexity measures assign low complexity
      values to random (incompressible) objects. As time grows, the stated complexity
      measures allow for the existence of complex states during the evolution of a
      computable dynamical system. We show, however, that finding these states involves
      undecidable computations. We conjecture that for similar complexity measures that
      assign low complexity values, decidability imposes comparable limits on the
      stable growth of complexity, and that such behavior is necessary for nontrivial
      evolutionary systems. We show that the undecidability of adapted states imposes
      novel and unpredictable behavior on the individuals or populations being modeled.
      Such behavior is irreducible. Finally, we offer an example of a system, first
      proposed by Chaitin, that exhibits strong OEE.

PMID- 29369711
TI  - The Biological Foundations of Enactivism: A Report on a Workshop Held at
      Artificial Life XV.
AB  - This is a report on the Biological Foundations of Enactivism Workshop, which was
      held as part of Artificial Life XV. The workshop aimed to revisit enactivism's
      contributions to biology and to revitalize the discussion of autonomy with the
      goal of grounding it in quantitative definitions based in observable phenomena.
      This report summarizes some of the important issues addressed in the workshop's
      talks and discussions, which include how to identify emergent individuals out of
      an environmental background, what the roles of autonomy and normativity are in
      biological theory, how new autonomous agents can spontaneously emerge at the
      origins of life, and what science can say about subjective experience.

PMID- 29369712
TI  - Report on the ISAL Special Session on ALife and Society, ALife XV, Cancun,
      Mexico, 2016.

PMID- 29369713
TI  - ALife and Society: Editorial Introduction to the Artificial Life Conference 2016
      Special Issue.

PMID- 29369714
TI  - Robustness and Contingent History: From Prisoner's Dilemma to Gaia Theory.
AB  - In both social systems and ecosystems there is a need to resolve potential
      conflicts between the interests of individuals and the collective interest of the
      community. The collective interests need to survive the turbulent dynamics of
      social and ecological interactions. To see how different systems with different
      sets of interactions have different degrees of robustness, we need to look at
      their different contingent histories. We analyze abstract artificial life models
      of such systems, and note that some prominent examples rely on explicitly
      ahistorical frameworks; we point out where analyses that ignore a contingent
      historical context can be fatally flawed. The mathematical foundations of Gaia
      theory are presented in a form whose very basic and general assumptions point to
      wide applicability across complex dynamical systems. This highlights surprising
      connections between robustness and accumulated contingent happenstance,
      regardless of whether Darwinian evolution is or is not implicated. Real-life
      studies highlight the role of history, and artificial life studies should do
      likewise.

PMID- 29369715
TI  - The Institutional Approach for Modeling the Evolution of Human Societies.
AB  - Artificial life is concerned with understanding the dynamics of human societies.
      A defining feature of any society is its institutions. However, defining exactly
      what an institution is has proven difficult, with authors often talking past each
      other. This article presents a dynamic model of institutions, which views them as
      political game forms that generate the rules of a group's economic interactions.
      Unlike most prior work, the framework presented here allows for the construction
      of explicit models of the evolution of institutional rules. It takes account of
      the fact that group members are likely to try to create rules that benefit
      themselves. Following from this, it allows us to determine the conditions under
      which self-interested individuals will create institutional rules that support
      cooperation-for example, that prevent a tragedy of the commons. The article
      finishes with an example of how a model of the evolution of institutional rewards
      and punishments for promoting cooperation can be created. It is intended that
      this framework will allow artificial life researchers to examine how human groups
      can themselves create conditions for cooperation. This will help provide a better
      understanding of historical human social evolution, and facilitate the resolution
      of pressing societal social dilemmas.

PMID- 29369716
TI  - Social Learning and Cultural Evolution in Artificial Life.
AB  - We describe the questions and discussions raised at the First Workshop on Social
      Learning and Cultural Evolution held at theArtificial Life Conference 2016 in
      Cancun, Mexico in July 2016. The purpose of the workshop was to assemble
      artificial life researchers interested in social learning and cultural evolution
      into one group so that we could focus on recent work and interesting open
      questions. Our discussion related to both the mechanisms of social learning and
      cultural evolution and the consequences and influence of social learning and
      cultural evolution on living systems. We present the contributions of our
      workshop presenters and conclude with a discussion of the more important open
      questions in this area.

PMID- 29369717
TI  - Accelerating research on treatment and services for transition age youth and
      adults on the autism spectrum.

PMID- 29369718
TI  - Editorial 1/2018.

PMID- 29369720
TI  - Confirmation of Echinococcus canadensis G8 and G10 in Idaho Gray Wolves ( Canis
      lupus) and Cervids.
AB  - We confirm the presence of Echinococcus canadensis genotypes G8 and G10 in gray
      wolves ( Canis lupus) and cervids in Idaho, US. Our results demonstrated that
      cystic echinococcosis remains a potential public health issue, indicating the
      need for regular deworming of domestic dogs, who often act as potential bridge
      hosts.

PMID- 29369721
TI  - NEUROPATHOLOGIC FINDINGS IN CETACEANS STRANDED IN ITALY (2002-14).
AB  - We summarized the neuropathologic findings in 60 cetaceans stranded along the
      Italian coastline from 2002 to 2014. The following neuropathologic changes were
      detected in 45% (27/60) of animals: nonsuppurative meningo-encephalitides (30%,
      18/60), nonspecific lesions (12%, 7/60), suppurative encephalitis (2%, 1/60), and
      neoplasm (2%, 1/60). No histologic lesions were found in 47% (28/60) of the
      specimens. Five (8%, 5/60) samples were unsuitable for analysis. Analysis with
      PCR detected Brucella spp., morbillivirus, and Toxoplasma gondii infection in
      one, six, and seven individuals, respectively. Immunohistochemical analysis
      confirmed positivity for morbillivirus and for T. gondii infection in three cases
      each. No evidence of the scrapie-associated prion protein PrPSc was detected. Our
      findings underscore the importance of an adequate surveillance system for
      monitoring aquatic mammal pathologies and for protecting both animal and human
      health.

PMID- 29369722
TI  - The Occurrence of Some Nonblood Protozoan Parasites in Wild and Domestic Mammals
      in South Africa.
AB  - Relatively little is known about protozoan parasites in African animals. Here we
      investigated the occurrence of protozoan parasites in mammals from South Africa.
      Oocysts of protozoan parasites were detected in 13 of 56 (23%) fecal samples
      using conventional microscopic examination methods. Cryptosporidium spp. and
      Cystoisospora spp. were detected in eight (14%) and five (9%) samples,
      respectively. Mixed parasitic infection of Cryptosporidium spp. and Cystoisospora
      spp. was recorded in banded mongoose ( Mungos mungo). Cryptosporidium spp. was
      detected for the first time in cheetah ( Acinonyx jubatus), spotted hyena (
      Crocuta crocuta), and African polecat ( Ictonyx striatus). Antibodies to
      Toxoplasma gondii and Neospora caninum were not detected by enzyme-linked
      immunosorbent assay in any of 32 sera tested. We detected T. gondii by PCR in
      tissues of five of 243 (2%) animals: domestic dog ( Canis lupus familiaris),
      gerbil ( Gerbilliscus spp.), greater kudu ( Tragelaphus strepsiceros), honey
      badger ( Mellivora capensis), and white-tailed mongoose ( Ichneumia albicauda).
      Our isolation of T. gondii from white-tailed mongoose and honey badger was a
      unique finding. All tissue samples were negative for N. caninum. The study
      increases our knowledge on the occurrence of protozoan parasites in populations
      of wild and domestic animals in South Africa.

PMID- 29369723
TI  - CHLAMYDIA PSITTACI IN FERAL ROSY-FACED LOVEBIRDS ( AGAPORNIS ROSEICOLLIS) AND
      OTHER BACKYARD BIRDS IN MARICOPA COUNTY, ARIZONA, USA.
AB  - In 2013, a mortality event of nonnative, feral Rosy-faced Lovebirds ( Agapornis
      roseicollis) in residential backyards in Maricopa County, Arizona, US was
      attributed to infection with Chlamydia psittaci. In June 2014, additional
      mortality occurred in the same region. Accordingly, in August 2014 we sampled
      live lovebirds and sympatric bird species visiting backyard bird feeders to
      determine the prevalence of DNA and the seroprevalence of antibodies to C.
      psittaci using real-time PCR-based testing and elementary body agglutination,
      respectively. Chlamydia psittaci DNA was present in conjunctival-choanal or
      cloacal swabs in 93% (43/46) of lovebirds and 10% (14/142) of sympatric birds.
      Antibodies to C. psittaci were detected in 76% (31/41) of lovebirds and 7%
      (7/102) of sympatric birds. Among the sympatric birds, Rock Doves ( Columba
      livia) had the highest prevalence of C. psittaci DNA (75%; 6/8) and
      seroprevalence (25%; 2/8). Psittacine circovirus 1 DNA was also identified, using
      real-time PCR-based testing, from the same swab samples in 69% (11/16) of species
      sampled, with a prevalence of 80% (37/46) in lovebirds and 27% (38/142) in
      sympatric species. The presence of either Rosy-faced Lovebirds or Rock Doves at
      residential bird feeders may be cause for concern for epizootic and zoonotic
      transmission of C. psittaci in this region.

PMID- 29369724
TI  - Identification of Hemotropic Mycoplasmas in an Eastern Box Turtle ( Terrapene
      carolina carolina) and a Yellow-bellied Slider ( Trachemys scripta scripta) from
      North Carolina, USA.
AB  - Mycoplasma spp. are known from several chelonian and other reptilian species. We
      determined if turtles obtained by the Turtle Rescue Team at North Carolina State
      University are carriers of hemotropic Mycoplasma or Bartonella spp. Spleen
      samples were collected at necropsy during May through July, 2014 from 53 turtles
      of seven species. All turtles were dead or were euthanized upon arrival due to
      severe traumatic injuries, or they died shortly after beginning treatment. We
      used PCR amplification for both bacterial genera; Bartonella spp. DNA was not
      amplified. Based upon sequencing of the 16S rRNA subunit, one eastern box turtle
      ( Terrapene carolina carolina) and one yellow-bellied slider ( Trachemys scripta
      scripta) were infected with Mycoplasma spp. that have genetic similarities to
      strains that infect other animals.

PMID- 29369726
TI  - Rare Osteochondroma Associated with Natural Mortality of a Wild White-Tailed Deer
      ( Odocoileus virginianus).
AB  - Within a 6-mo period, a radio-collared, white-tailed deer ( Odocoileus
      virginianus) doe from Delaware, US, developed a fatal head mass consistent with
      osteochondroma. We suspected a retroviral etiology, but test results were
      negative. Population implications were not suspected, but this case is concerning
      as these tumors are not thought to cause mortality.

PMID- 29369725
TI  - Use of Blood-soaked Cellulose Filter Paper for Measuring Carbon and Nitrogen
      Stable Isotopes.
AB  - We explored the use of filter paper soaked in whole blood for measuring carbon
      (C) and nitrogen (N) stable isotopes, often used in feeding ecology or diet
      studies, to better understand drivers of exposure to contaminants. Our results
      showed no statistically or biologically relevant differences in C and N stable
      isotope measures between our gold standard (whole blood with anticoagulant) and
      eluates from processed, blood-soaked filter paper. Our data supported the
      effectiveness of using filter paper for assessing C and N stable isotopes in
      blood to address feeding ecology and other uses. The ease of sampling and
      processing should allow blood-soaked filter paper to be used in sampling of live
      (e.g., captured, stranded) and lethally taken (e.g., hunter-killed) wild
      vertebrates.

PMID- 29369727
TI  - Respiratory Mites ( Orthohalarachne diminuata) and beta-hemolytic Streptococci
      Associated Bronchopneumonia Outbreak in South American Fur Seal Pups (
      Arctocephalus australis).
AB  - Although mites of the Orthohalarachne genus are common parasites of otariids,
      their role as agents of disease and in causing population-level mortality is
      unknown. In the austral summer of 2016, there was an increase in mortality among
      South American fur seal ( Arctocephalus australis) pups at Guafo Island, Northern
      Chilean Patagonia. Pups found dead or terminally ill had moderate to marked,
      multifocal, mucopurulent bronchopneumonia associated with large numbers of
      respiratory mites ( Orthohalarachne diminuata) and rare Gram-positive cocci. In
      lung areas less affected by bronchopneumonia, acute interstitial pneumonia with
      marked congestion and scant hemorrhage was evident. Bacteria from pups dying of
      bronchopneumonia were isolated and identified as Streptococcus marimammalium and
      Streptococcus canis. Respiratory mites obstructed airflow, disrupted airway
      epithelial lining, and likely facilitated the proliferation of pathogenic beta
      hemolytic streptococci, leading to severe bronchopneumonia and death of fur seal
      pups. An abrupt increase in sea surface temperature in Guafo Island corresponded
      to the timing of the bronchopneumonia outbreak. The potential role of
      environmental factors in the fur seal pup mortality warrants further study.

PMID- 29369728
TI  - Introduction and Establishment of Raccoon Rabies on Islands: Jekyll Island,
      Georgia, USA as a Case Study.
AB  - The introduction of rabies virus (RABV) to barrier islands, which are often
      popular tourist destinations with resource-rich habitats and connectivity and
      proximity to the mainland, is especially concerning because it can easily become
      endemic due to factors like dense rabies-vector populations (e.g., raccoons [
      Procyon lotor]), high inter- and intraspecies contact rates, and anthropogenic
      activities such as supplemental feeding of feral cats ( Felis catus). In January
      2013, a neurologic raccoon found on the Jekyll Island (JI), Georgia, US causeway
      tested positive for rabies. Mortality investigations of 29 raccoons have been
      conducted between December 2012-May 2017. The two most common diagnoses were RABV
      ( n=11) and canine distemper virus (CDV; n=8). Parvoviral enteritis was diagnosed
      in four raccoons but no coinfections were diagnosed. There was no apparent
      seasonality for rabies cases, but all CDV cases occurred in spring-fall. Most
      (64%) rabies submissions came from residential or recreational use areas located
      near feral cat feeding stations. Jekyll Island is a popular destination where
      tourists engage in numerous outdoor activities which facilitate human-wildlife
      interactions. Concerns regarding public and animal health highlight the
      importance of rabies surveillance, prevention, and control on islands. This is
      the first report of rabies on JI and emphasizes the importance of disease
      investigations because the assumption that neurologic raccoons have CDV, an
      endemic pathogen, can miss the establishment of novel pathogens such as RABV.

PMID- 29369729
TI  - DEVELOPMENT AND VALIDATION OF QUANTITATIVE PCR ASSAYS TO MEASURE CYTOKINE
      TRANSCRIPT LEVELS IN THE FLORIDA MANATEE ( TRICHECHUS MANATUS LATIROSTRIS).
AB  - Cytokines have important roles in the mammalian response to viral and bacterial
      infections, trauma, and wound healing. Because of early cytokine production after
      physiologic stresses, the regulation of messenger RNA (mRNA) transcripts can be
      used to assess immunologic responses before changes in protein production. To
      detect and assess early immune changes in endangered Florida manatees (
      Trichechus manatus latirostris), we developed and validated a panel of
      quantitative PCR assays to measure mRNA transcription levels for the cytokines
      interferon (IFN)-gamma; interleukin (IL)-2, -6, and -10; tumor necrosis factor
      alpha; and the housekeeping genes glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) and beta-actin (reference genes). Assays were successfully validated
      using blood samples from free-ranging, apparently healthy manatees from the east
      and west coasts of central Florida, US. No cytokine or housekeeping gene
      transcription levels were significantly different among age classes or sexes.
      However, the transcription levels for GAPDH, IL-2, IL-6, and IFN-gamma were
      significantly higher ( P<0.05) in manatees from the east coast of Florida than
      they were from those from the west coast. We found IL-10 and beta-actin to be
      consistent between sites and identified beta-actin as a good candidate for use as
      a reference gene in future studies. Our assays can aid in the investigation of
      manatee immune response to physical trauma and novel or ongoing environmental
      stressors.

PMID- 29369730
TI  - Keeping Expectations in Check With Immune Checkpoint Inhibitors.

PMID- 29369731
TI  - Web-Based Stress Management for Newly Diagnosed Patients With Cancer (STREAM): A
      Randomized, Wait-List Controlled Intervention Study.
AB  - Purpose Being diagnosed with cancer causes major psychological distress; however,
      a majority of patients lack psychological support during this critical period.
      Internet interventions help patients overcome many barriers to seeking face-to
      face support and may thus close this gap. We assessed feasibility and efficacy of
      Web-based stress management (STREAM [Stress-Aktiv-Mindern]) for newly diagnosed
      patients with cancer. Patients and Methods In a randomized controlled trial,
      patients with cancer who had started first-line treatment within the previous 12
      weeks were randomly assigned to a therapist-guided Web-based intervention or a
      wait-list (control), stratified according to distress level (>= 5 v < 5 on scale
      of 0 to 10). Primary efficacy end point was quality of life after the
      intervention (Functional Assessment of Chronic Illness Therapy-Fatigue).
      Secondary end points included distress (Distress Thermometer) and anxiety or
      depression (Hospital Anxiety and Depression Scale). Treatment effect was assessed
      with analyses of covariance, adjusted for baseline distress. Results A total of
      222 of 229 screened patients applied online for participation. Between September
      2014 and November 2016, 129 newly diagnosed patients with cancer, including 92
      women treated for breast cancer, were randomly assigned to the intervention (n =
      65) or control (n = 64) group. Adherence was good, with 80.0% of patients using
      >= six of eight modules. Psychologists spent 13.3 minutes per week (interquartile
      range, 9.5-17.9 minutes per week) per patient for online guidance. After the
      intervention, quality of life was significantly higher (Functional Assessment of
      Chronic Illness Therapy-Fatigue: mean, 8.59 points; 95% CI, 2.45 to 14.73 points;
      P = .007) and distress significantly lower (Distress Thermometer: mean, -0.85;
      95% CI, -1.60 to -0.10; P = .03) in the intervention group as compared with the
      control. Changes in anxiety or depression were not significant in the intention
      to-treat population (Hospital Anxiety and Depression Scale: mean, -1.28; 95% CI, 
      3.02 to 0.45; P = .15). Quality of life increased in the control group with the
      delayed intervention. Conclusion The Web-based stress management program STREAM
      is feasible and effective in improving quality of life.

PMID- 29369732
TI  - PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a
      Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of
      Endocrine Therapy for Hormone Receptor-Positive Early Breast Cancer.
AB  - Purpose The PAM50-based Prosigna risk of recurrence (ROR) score has been
      validated in randomized clinical trials to predict 10-year distant recurrence
      (DR). The value of Prosigna for predicting DR was examined in a comprehensive
      nationwide Danish cohort consisting of postmenopausal women with hormone receptor
      positive early breast cancer treated with 5 years of endocrine therapy alone.
      Patients and Methods Using the population-based Danish Breast Cancer Cooperative
      Group database, follow-up data were collected on all patients diagnosed from 2000
      through 2003 who, by nationwide guidelines, were treated with endocrine therapy
      for 5 years. Primary tumor blocks from 2,740 patients were tested with Prosigna
      and, after determination of human epidermal growth factor receptor 2 (HER2)
      status, data from 2,558 hormone receptor-positive/HER2-negative samples were
      analyzed, including 1,395 node-positive patients. Fine and Gray models were
      applied to determine the prognostic value of ROR for DR. Results Median follow-up
      for recurrence was 9.2 years. Twenty-six percent of the node-positive patients
      were classified as low ROR (n = 359) with a DR risk of 3.5% (95% confidence
      interval [CI], 1.9% to 6.1%) versus a DR risk of 22.1% (95% CI, 18.6% to 25.8%)
      at 10 years for patients classified as high ROR (n = 648). Node-negative patients
      classified as low and high ROR had a risk of DR of 5.0% (95% CI, 2.9% to 8.0%)
      and 17.8% (95% CI, 14.0% to 22.0%), respectively. Luminal B tumors (n = 947; DR
      risk, 18.4% [95% CI: 15.7% to 21.3%]) had a significantly worse outcome than
      luminal A tumors (n = 1,474,;DR risk, 7.6% [95% CI: 6.1% to 9.2%]; P < .001).
      Conclusion Prosigna ROR score improved the prediction of outcome in this
      nationwide Danish population. In a real-world setting, Prosigna can reliably
      identify node-negative patients and a significant proportion of patients with one
      to three positive nodes who can be spared treatment with adjuvant chemotherapy.

PMID- 29369733
TI  - Clinical applications of ultra-high field magnetic resonance imaging in multiple
      sclerosis.
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) is of paramount importance for the
      early diagnosis of multiple sclerosis (MS) and MRI findings are part of the MS
      diagnostic criteria. There is a growing interest in the use of ultra-high-field
      strength -7 Tesla- (7T) MRI to investigate, in vivo, the pathological substrate
      of the disease. Areas covered: An overview of 7T MRI applications in MS focusing
      on increased sensitivity for lesion detection, specificity of the central vein
      sign and better understanding of MS pathophysiology. Implications for disease
      diagnosis, monitoring and treatment planning are discussed. Expert commentary: 7T
      MRI provides increased signal-to-noise and contrast-to-noise-ratio that allow
      higher spatial resolution and better detection of anatomical and pathological
      features. The high spatial resolution reachable at 7T has been a game changer for
      neuroimaging applications not only in MS but also in epilepsy, brain tumors,
      dementia, and neuro-psychiatric disorders. Furthermore, the first 7T device has
      recently been cleared for clinical use by the food and drug administration.

PMID- 29369734
TI  - Call for Manuscripts for technology special issue.

PMID- 29369735
TI  - Mental Health Staff Perceptions and Practice Regarding Self-Harm, Suicidality and
      Help-Seeking in LGBTQ Youth: Findings from a Cross-Sectional Survey in the UK.
AB  - Young people who identify as lesbian, gay, bisexual, transgender or queer (LGBTQ)
      experience higher levels of suicidality compared to heterosexual or cisgender
      peers, and face significant barriers accessing mental health services including
      prejudice from staff. In a cross-sectional survey, mental health staff who
      reported receiving LGBT awareness training were significantly more likely to
      report in relation to working with LGBT youth that they routinely discussed
      issues of sexuality and gender (chi2=8.782, df=2, p < 0.05); to feel that their
      organisation supported them to work with this group (chi2=14.401, df=2, p <
      0.001); and report that they had access to adequate skills training that
      supported their work with suicidality and self-harm with this group (chi2=21.911,
      df=2, p <0.001). There is a need to enhance the mental health workforce in LGBTQ
      awareness, and these findings indicate that awareness training could impact
      positively on practice.

PMID- 29369736
TI  - Effect of Laparoscopic Surgery on Quality of Life in Ulcerative Colitis.
AB  - AIM: To evaluate quality of life after surgery for ulcerative colitis (UC) the
      gastroenterological and psychological conditions were examined. MATERIALS AND
      METHODS: Between January 1, 2005 and March 1, 2016, surgery was performed for UC
      in a total of 75 patients. Our examinations were performed in 58 cases. Quality
      of life was examined with questionnaires. Functional Scoring System,
      Gastrointestinal Quality of Life Index (GIQLI), and Short Inflammatory Bowel
      Disease Questionnaire (SIBDQ) were used for testing gastroenterological
      conditions; Spielberger's State-Trait Anxiety Questionnaire, Beck Depression
      Inventory, and Brief Illness Perception Questionnaire (BIPQ) were performed to
      consider psychological status. RESULTS: Trait anxiety and the incidence of
      abdominal pain were significantly lower in patients having undergone laparoscopic
      surgery. No difference was found between the minimally invasive and conventional
      methods in the early complications. There were significantly more late
      complications developing after 30 days in patients who had undergone open
      surgery. Differences were found in personal control between patients with a stoma
      and patients without a stoma. Patients with a stoma felt they had less control
      over their disease. A significant correlation was found between the results of
      the psychological and gastrointestinal questionnaires. CONCLUSIONS: Minimally
      invasive technique provides a better long-term outcome for patients with UC,
      fewer complications, and a more balanced emotional condition. Favorable
      gastroenterological condition leads to better psychological status, which is
      negatively influenced by stoma or complications.

PMID- 29369737
TI  - Pharmacology of Serotonin Receptors Causing Contraction of Isolated Bovine
      Posterior Ciliary Arteries: Role in Ocular Blood Flow.
AB  - PURPOSE: To determine the serotonergic (5HT) receptor subtype mediating the
      contraction of bovine posterior ciliary arteries (BPCAs) in vitro. METHODS:
      Longitudinal isometric tension was measured in BPCA strips (4-5 mm) mounted in 25
      mL organ baths containing oxygenated Krebs solution at 37 degrees C. Cumulative
      contractile concentration-response (C-R) curves were generated for various 5-HT
      agonists to assess their potencies and maximal degrees of contraction. Multiple
      agonist C-R curves were also constructed in the presence and absence of receptor
      selective antagonists to determine antagonist potencies using Schild plots.
      RESULTS: Selective and nonselective agonists for 5-HT receptors elicited
      concentration-dependent contractile responses in BPCAs with the following rank
      order of potency: MK-212 > BW723C86 > alpha-methyl-5-HT >5-methoxy-alpha-5-methyl
      5-HT >> R-DO1 > >5-HT >> cabergoline >> 5-methoxy-dimethyl-tryptamine >> 2-methyl
      5-HT >> tryptamine. Interestingly, both 8-OH-DPAT (5HT1A agonist) and quipazine
      (5HT3 agonist) did not elicit contractions in BPCAs. The contractions produced by
      BW723C86 (5-HT2B agonist) were antagonized by 5-HT receptor blockers, RS-127445
      (5-HT2B antagonist), and M-100907 (5-HT2A antagonist), yielding antagonist pA2
      values of 7.5 +/- 0.12 (n = 4) and 6.2 +/- 0.17 (n = 4), respectively.
      Furthermore, contractions elicited by MK-212 (5-HT2C agonist) was blocked by RS
      102221 (5-HT2C antagonist), although noncompetitively. CONCLUSIONS: On the basis
      of the pharmacological profile of selective agonists and antagonists, we conclude
      that serotonin-induced contractions of the BPCA are mediated primarily by a
      combination of 5HT2C and/or 5HT2B receptors. It appears that 5-HT1A and 5-HT3
      receptors are not involved in the contractile action of BPCAs to serotonin.

PMID- 29369738
TI  - Sex and nitric oxide bioavailability interact to modulate interstitial Po2 in
      healthy rat skeletal muscle.
AB  - Premenopausal women express reduced blood pressure and risk of cardiovascular
      disease relative to age-matched men. This purportedly relates to elevated
      estrogen levels increasing nitric oxide synthase (NOS) activity and NO-mediated
      vasorelaxation. We tested the hypotheses that female rat skeletal muscle would:
      1) evince a higher O2 delivery-to-utilization ratio (Qo2/Vo2) during
      contractions; and 2) express greater modulation of Qo2/Vo2 with changes to NO
      bioavailability compared with male rats. The spinotrapezius muscle of Sprague
      Dawley rats (females = 8, males = 8) was surgically exposed and electrically
      stimulated (180 s, 1 Hz, 6 V). OxyphorG4 was injected into the muscle and
      phosphorescence quenching employed to determine the temporal profile of
      interstitial Po2 (Po2is, determined by Qo2/Vo2). This was performed under three
      conditions: control (CON), 300 uM sodium nitroprusside (SNP; NO donor), and 1.5
      mM Nomega-nitro-l-arginine methyl ester (l-NAME; NOS blockade) superfusion. No
      sex differences were found for the Po2is kinetics parameters in CON or l-NAME ( P
      > 0.05), but females elicited a lower baseline following SNP (males 42 +/- 3 vs.
      females 36 +/- 2 mmHg, P < 0.05). Females had a lower DeltaPo2is during
      contractions following SNP (males 22 +/- 3 vs. females 17 +/- 2 mmHg, P < 0.05),
      but there were no sex differences for the temporal response to contractions ( P >
      0.05). The total NO effect (SNP minus l-NAME) on Po2is was not different between
      sexes. However, the spread across both conditions was shifted to a lower absolute
      range for females (reduced SNP baseline and greater reduction following l-NAME).
      These data support that females have a greater reliance on basal NO
      bioavailability and males have a greater responsiveness to exogenous NO and less
      responsiveness to reduced endogenous NO. NEW & NOTEWORTHY Interstitial Po2
      (Po2is; determined by O2 delivery-to-utilization matching) plays an important
      role for O2 flux into skeletal muscle. We show that both sexes regulate Po2is at
      similar levels at rest and during skeletal muscle contractions. However,
      modulating NO bioavailability exposes sex differences in this regulation with
      females potentially having a greater reliance on basal NO bioavailability and
      males having a greater responsiveness to exogenous NO and less responsiveness to
      reduced endogenous NO.

PMID- 29369740
TI  - Exploring kinetic energy as a new marker of cardiac function in the single
      ventricle circulation.
AB  - Ventricular volumetric ejection fraction (VV EF) is often normal in patients with
      single ventricle circulations despite them experiencing symptoms related to
      circulatory failure. We sought to determine if kinetic energy (KE) could be a
      better marker of ventricular performance. KE was prospectively quantified using
      four-dimensional flow MRI in 41 patients with a single ventricle circulation
      (aged 0.5-28 yr) and compared with 43 healthy volunteers (aged 1.5-62 yr) and 14
      patients with left ventricular (LV) dysfunction (aged 28-79 yr). Intraventricular
      end-diastolic blood was tracked through systole and divided into ejected and
      residual blood components. Two ejection fraction (EF) metrics were devised based
      on the KE of the ejected component over the total of both the ejected and
      residual components using 1) instantaneous peak KE to assess KE EF or 2)
      summating individual peak particle energy (PE) to assess PE EF. KE EF and PE EF
      had a smaller range than VV EF in healthy subjects (97.9 +/- 0.8 vs. 97.3 +/- 0.8
      vs. 60.1 +/- 5.2%). LV dysfunction caused a fall in KE EF ( P = 0.01) and PE EF (
      P = 0.0001). VV EF in healthy LVs and single ventricle hearts was equivalent;
      however, KE EF and PE EF were lower ( P < 0.001) with a wider range indicating a
      spectrum of severity. Those reporting the greatest symptomatic impairment (New
      York Heart Association II) had lower PE EF than asymptomatic subjects ( P =
      0.0067). KE metrics are markers of healthy cardiac function. PE EF may be useful
      in grading dysfunction. NEW & NOTEWORTHY Kinetic energy (KE) represents the
      useful work of the heart in ejecting blood. This article details the utilization
      of KE indexes to assess cardiac function in health and a variety of
      pathophysiological conditions. KE ejection fraction and particle energy ejection
      fraction (PE EF) showed a narrow range in health and a lower wider range in
      disease representing a spectrum of severity. PE EF was altered by functional
      status potentially offering the opportunity to grade dysfunction.

PMID- 29369739
TI  - Organ-level right ventricular dysfunction with preserved Frank-Starling mechanism
      in a mouse model of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a rapidly fatal disease in which
      mortality is due to right ventricular (RV) failure. It is unclear whether RV
      dysfunction initiates at the organ level or the subcellular level or both. We
      hypothesized that chronic pressure overload-induced RV dysfunction begins at the
      organ level with preserved Frank-Starling mechanism in myocytes. To test this
      hypothesis, we induced PAH with Sugen + hypoxia (HySu) in mice and measured RV
      whole organ and subcellular functional changes by in vivo pressure-volume
      measurements and in vitro trabeculae length-tension measurements, respectively,
      at multiple time points for up to 56 days. We observed progressive changes in RV
      function at the organ level: in contrast to early PAH (14-day HySu), in late PAH
      (56-day HySu) ejection fraction and ventricular-vascular coupling were decreased.
      At the subcellular level, direct measurements of myofilament contraction showed
      that RV contractile force was similarly increased at any stage of PAH
      development. Moreover, cross-bridge kinetics were not changed and length
      dependence of force development (Frank-Starling relation) were not different from
      baseline in any PAH group. Histological examinations confirmed increased
      cardiomyocyte cross-sectional area and decreased von Willebrand factor expression
      in RVs with PAH. In summary, RV dysfunction developed at the organ level with
      preserved Frank-Starling mechanism in myofilaments, and these results provide
      novel insight into the development of RV dysfunction, which is critical to
      understanding the mechanisms of RV failure. NEW & NOTEWORTHY A multiscale
      investigation of pulmonary artery pressure overload in mice showed time-dependent
      organ-level right ventricular (RV) dysfunction with preserved Frank-Starling
      relations in myofilaments. Our findings provide novel insight into the
      development of RV dysfunction, which is critical to understanding mechanisms of
      RV failure.

PMID- 29369741
TI  - Reflex bronchoconstriction evoked by inhaled nicotine aerosol in guinea pigs:
      role of the nicotinic acetylcholine receptor.
AB  - Inhaled cigarette smoke stimulated vagal bronchopulmonary C fibers via an action
      of nicotine on neuronal nicotinic acetylcholine receptor (nAChR). Recent studies
      have reported that nicotine at high concentrations can also activate the
      transient receptor potential ankyrin 1 receptor (TRPA1) expressed in these
      sensory nerves. This study was performed to characterize the airway response to
      inhaled nicotine aerosol and to investigate the relative roles of nAChR and TRPA1
      in this response. Guinea pigs were anesthetized and mechanically ventilated; one
      tidal volume of nicotine aerosol (2% solution) was diluted by an equal volume of
      air and delivered directly into the lung via a tracheal cannula in a single
      breath. Our results showed the following: 1) Inhalation of nicotine aerosol
      triggered an immediate and pronounced bronchoconstriction; the increase in total
      pulmonary resistance reached a peak of 588 +/- 205% (mean +/- SE) in 10-40 s,
      which gradually returned to baseline after 1-5 min. 2) Pretreatment with either
      atropine (iv) or mecamylamine (aerosol) almost completely abolished the nicotine
      induced bronchoconstriction; the mecamylamine pretreatment did not block the
      bronchoconstriction and bradycardia evoked by electrical stimulation of the
      distal end of one sectioned vagus nerve, indicating its minimal systemic effects.
      3) Pretreatment with HC-030031, a selective TRPA1 antagonist, abolished the
      bronchoconstriction induced by allyl isothiocyanate, a selective TRPA1 agonist,
      but did not attenuate the nicotine-evoked bronchoconstriction. In conclusion,
      inhalation of a single breath of nicotine aerosol evoked acute
      bronchoconstriction mediated through the cholinergic reflex pathway. This reflex
      response was triggered by activation of nAChR, but not TRPA1, located in airway
      sensory nerves. NEW & NOTEWORTHY Recent reports revealed that nicotine at high
      concentration activated transient receptor potential ankyrin 1 receptor (TRPA1)
      expressed in vagal bronchopulmonary sensory nerves. This study showed that
      inhalation of a single breath of nicotine aerosol consistently evoked acute
      bronchoconstriction that was mediated through the cholinergic reflex pathway and
      triggered by activation of nicotinic acetylcholine receptor, but not TRPA1,
      located in these nerves. This is new and important information considering the
      recent rapid and alarming rise in the prevalence of e-cigarette use for nicotine
      inhalation.

PMID- 29369742
TI  - Cross-validation and out-of-sample testing of physical activity intensity
      predictions with a wrist-worn accelerometer.
AB  - Wrist-worn accelerometers are gaining popularity for measurement of physical
      activity. However, few methods for predicting physical activity intensity from
      wrist-worn accelerometer data have been tested on data not used to create the
      methods (out-of-sample data). This study utilized two previously collected data
      sets [Ball State University (BSU) and Michigan State University (MSU)] in which
      participants wore a GENEActiv accelerometer on the left wrist while performing
      sedentary, lifestyle, ambulatory, and exercise activities in simulated free
      living settings. Activity intensity was determined via direct observation. Four
      machine learning models (plus 2 combination methods) and six feature sets were
      used to predict activity intensity (30-s intervals) with the accelerometer data.
      Leave-one-out cross-validation and out-of-sample testing were performed to
      evaluate accuracy in activity intensity prediction, and classification accuracies
      were used to determine differences among feature sets and machine learning
      models. In out-of-sample testing, the random forest model (77.3-78.5%) had higher
      accuracy than other machine learning models (70.9-76.4%) and accuracy similar to
      combination methods (77.0-77.9%). Feature sets utilizing frequency-domain
      features had improved accuracy over other feature sets in leave-one-out cross
      validation (92.6-92.8% vs. 87.8-91.9% in MSU data set; 79.3-80.2% vs. 76.7-78.4%
      in BSU data set) but similar or worse accuracy in out-of-sample testing (74.0
      77.4% vs. 74.1-79.1% in MSU data set; 76.1-77.0% vs. 75.5-77.3% in BSU data set).
      All machine learning models outperformed the euclidean norm minus one/GGIR method
      in out-of-sample testing (69.5-78.5% vs. 53.6-70.6%). From these results, we
      recommend out-of-sample testing to confirm generalizability of machine learning
      models. Additionally, random forest models and feature sets with only time-domain
      features provided the best accuracy for activity intensity prediction from a
      wrist-worn accelerometer. NEW & NOTEWORTHY This study includes in-sample and out
      of-sample cross-validation of an alternate method for deriving meaningful
      physical activity outcomes from accelerometer data collected with a wrist-worn
      accelerometer. This method uses machine learning to directly predict activity
      intensity. By so doing, this study provides a classification model that may avoid
      high errors present with energy expenditure prediction while still allowing
      researchers to assess adherence to physical activity guidelines.

PMID- 29369743
TI  - Rate of Symptomatic Intracerebral Hemorrhage Related to Intravenous tPA
      Administered Over Telestroke Within 4.5-Hour Window.
AB  - BACKGROUND: Intravenous tissue plasminogen activator (tPA) remains the
      cornerstone medical treatment for acute ischemic stroke. The establishment of
      telestroke technology has allowed patients presenting to hospitals that lack
      expert stroke care to be evaluated and receive tPA. The safety of tPA
      administered through telestroke has been evaluated only when tPA is given within
      the 3-h window of last known normal. The purpose of this study is to evaluate the
      safety of tPA when administered through telestroke within a 4.5-h window.
      METHODS: A retrospective analysis on the prospectively collected database for all
      patients who received tPA at the Medical University of South Carolina
      Comprehensive Stroke Center (MUSC) (hub), as well as the MUSC telestroke network
      partner hospitals (spokes), was performed. Collected data included demographics,
      baseline characteristics, time from last known well to tPA administration, and
      symptomatic intracerebral hemorrhage (sICH) rates. Logistic regression was used
      to examine the odds of a sICH in patients at spoke sites compared with the hub
      controlling for patient stroke severity, gender, age, and race. RESULTS: A total
      of 830 patients were identified. Median National Institute of Health Stroke Scale
      was significantly higher among patients treated at the hub (9 vs. 8, p = 0.013),
      and the hub treated a higher percentage of nonwhite patients (p = 0.039). sICH
      occurred in 27 (4.8%) in the spoke group and 10 (3.8%) in the hub group (p =
      0.523). Logistic regression results found no significant difference in the odds
      of sICH if tPA is given in a spoke site. CONCLUSIONS: Our study shows similar
      rates of sICH when intravenous tPA is administered at spokes through telestroke
      network compared with the hub.

PMID- 29369745
TI  - Lipid Nanoparticle Packaging Is an Effective and Nontoxic mRNA Delivery Platform
      in Embryonic Zebrafish.
AB  - Lipid nanoparticles (LNPs) are an attractive platform for the delivery of
      therapeutic RNA molecules because LNPs are versatile, have been validated in
      clinical trials, and are well tolerated. Here, we test whether LNPs can be used
      to deliver a reporter green fluorescent protein (gfp) mRNA to different tissues
      in zebrafish embryos. We show that LNP-packaged gfp mRNA can be delivered,
      through injection, and taken up by cells in multiple tissues in zebrafish embryos
      without any apparent detrimental effects on embryonic health or survival.
      Zebrafish embryos injected with LNP-packaged gfp mRNA show subsequent GFP
      expression in neural, vascular, cardiac, and skeletal muscle tissue, depending on
      injection site. In contrast, comparable naked (nonpackaged) gfp mRNA injections
      lead to little or no GFP expression. This study shows that LNPs can be used as an
      mRNA delivery platform in zebrafish and thus provides a basis for testing the
      therapeutic functions of LNP-packaged candidate mRNAs in the increasingly diverse
      array of zebrafish disease models.

PMID- 29369744
TI  - Changes to Extender, Cryoprotective Medium, and In Vitro Fertilization Improve
      Zebrafish Sperm Cryopreservation.
AB  - Sperm cryopreservation is a highly efficient method for preserving genetic
      resources. It extends the reproductive period of males and significantly reduces
      costs normally associated with maintenance of live animal colonies. However,
      previous zebrafish (Danio rerio) cryopreservation methods have produced variable
      outcomes and low post-thaw fertilization rates. To improve post-thaw
      fertilization rates after cryopreservation, we developed a new extender and
      cryoprotective medium (CPM), introduced quality assessment (QA), determined the
      optimal cooling rate, and improved the post-thaw in vitro fertilization process.
      We found that the hypertonic extender E400 preserved motility of sperm held on
      ice for at least 6 h. We implemented QA by measuring sperm cell densities with a
      NanoDrop spectrophotometer and sperm motility with computer-assisted sperm
      analysis (CASA). We developed a CPM, RMMB, which contains raffinose, skim milk,
      methanol, and bicine buffer. Post-thaw motility indicated that the optimal
      cooling rate in two types of cryogenic vials was between 10 and 15 degrees C/min.
      Test thaws from this method produced average motility of 20% +/- 13% and an
      average post-thaw fertilization rate of 68% +/- 16%.

PMID- 29369746
TI  - Re: Trends in the Prevalence of Severe Obesity and Bariatric Surgery Access: A
      State-Level Analysis from 2011 to 2014(J Laparoendosc Adv Surg Tech A 2017;27:669
      675).

PMID- 29369747
TI  - Survival of Bacterial and Parasitic Pathogens from Zebrafish (Danio rerio) After
      Cryopreservation and Thawing.
AB  - Cryopreservation is a common method used to preserve the sperm of various animal
      species, and it is widely used with zebrafish (Danio rerio). As with other
      animals, there is a possibility of paternal pathogen transmission through sperm.
      We evaluated the ability of five common and important pathogens of zebrafish to
      survive cryopreservation as used with zebrafish sperm and freezing without
      cryopreservant. We evaluated Mycobacterium chelonae, Mycobacterium marinum, and
      Edwardsiella ictaluri, each originally isolated from zebrafish, eggs of
      Pseuodocapillaria tomentosa, and spores of Pseudoloma neurophilia. Each
      mycobacterial isolate showed relatively minimal reduction in survival after
      freezing and thawing, particularly when subjected to cryopreservation. E.
      ictaluri also showed survival after cryopreservation, but exhibited a several log
      reduction after freezing at -80 degrees C without cryopreservant. With P.
      neurophilia, two separate experiments conducted 3 years apart yielded very
      similar results, showing some, but reduced, survival of spores by using three
      different viability assays: SYTOX stain, Fungi-Fluor stain, and presence of a
      spore vacuole. Eggs of P. tomentosa showed no survival based on larvation of eggs
      when subjected to either freezing method. Given that four of the five pathogens
      exhibited survival after cryopreservation, we recommend that sperm samples or
      donor male zebrafish fish be tested for pathogens when sperm are to be stored by
      using cryopreservation.

PMID- 29369748
TI  - Modulation of Cortisol Responses to an Acute Stressor in Zebrafish Visually
      Exposed to Heterospecific Fish During Development.
AB  - Studies regarding predator-prey relationships have often focused on prey
      assessment and the responses to predation risk, but few have verified the
      relationship in the presence or absence of visual contact with a predator (e.g.,
      tiger oscar, Astronotus ocellatus) or a nonpredator (e.g., goldfish, Carassius
      auratus) during the developmental phase, which could alter several physiological
      and neuroendocrine mechanisms in adulthood. Herein, we determined responses to
      physical (chasing with a net) and biological stressors (visualization to
      predator) in adult zebrafish raised in visual contact with a predator or
      nonpredator fish. We demonstrated that adult naive zebrafish show a more intense
      cortisol stress response than fish housed in visual contact with the stimulus
      fish (predator or nonpredator) when larvae, and that this alteration is related
      with movement specificity of the stimulus fish.

PMID- 29369749
TI  - Calorie Labeling Promotes Dietary Self-Control by Shifting the Temporal Dynamics
      of Health- and Taste-Attribute Integration in Overweight Individuals.
AB  - Understanding why people make unhealthy food choices and how to promote healthier
      choices is critical to prevent obesity. Unhealthy food choices may occur when
      individuals fail to consider health attributes as quickly as taste attributes in
      their decisions, and this bias may be modifiable by health-related external cues.
      One hundred seventy-eight participants performed a mouse-tracking food-choice
      task with and without calorie information. With the addition of calorie
      information, participants made healthier choices. Without calorie information,
      the initial integration of health attributes in overweight individuals' decisions
      was about 230 ms delayed relative to the taste attributes, but calorie labeling
      promoted healthier choices by speeding up the integration of health attributes
      during a food-choice task. Our study suggests that obesogenic choices are related
      to the relative speed with which taste and health attributes are integrated into
      the decision process and that this bias is modifiable by external health-related
      cues.

PMID- 29369750
TI  - Opinion: Making Inactivated and Subunit-Based Vaccines Work.
AB  - Empirically derived vaccines have in the past relied on the isolation and growth
      of disease-causing microorganisms that are then inactivated or attenuated before
      being administered. This is often done without prior knowledge of the mechanisms
      involved in conferring protective immunity. Recent advances in scientific
      technologies and in our knowledge of how protective immune responses are induced
      enable us to rationally design novel and safer vaccination strategies. Such
      advances have accelerated the development of inactivated whole-organism- and
      subunit-based vaccines. In this review, we discuss ideal attributes and criteria
      that need to be considered for the development of vaccines and some existing
      vaccine platforms. We focus on inactivated vaccines against influenza virus and
      ways by which vaccine efficacy can be improved with the use of adjuvants and Toll
      like receptor-2 signaling.

PMID- 29369751
TI  - Extent of BOLD Vascular Dysregulation Is Greater in Diffuse Gliomas without
      Isocitrate Dehydrogenase 1 R132H Mutation.
AB  - Purpose To determine the effect that R132H mutation status of diffuse glioma has
      on extent of vascular dysregulation and extent of residual blood oxygen level
      dependent (BOLD) abnormality after surgical resection. Materials and Methods This
      study was an institutional review board-approved retrospective analysis of an
      institutional database of patients, and informed consent was waived. From 2010 to
      2017, 39 treatment-naive patients with diffuse glioma underwent preoperative echo
      planar imaging and BOLD functional magnetic resonance imaging. BOLD vascular
      dysregulation maps were made by identifying voxels with time series similar to
      tumor and dissimilar to healthy brain. The spatial overlap between tumor and
      vascular dysregulation was characterized by using the Dice coefficient, and areas
      of BOLD abnormality outside the tumor margins were quantified as BOLD-only
      fraction (BOF). Linear regression was used to assess effects of R132H status on
      the Dice coefficient, BOF, and residual BOLD abnormality after surgical
      resection. Results When compared with R132H wild-type (R132H-) gliomas, R132H
      mutated (R132H+) gliomas showed greater spatial overlap between BOLD abnormality
      and tumor (mean Dice coefficient, 0.659 +/- 0.02 [standard error] for R132H+ and
      0.327 +/- 0.04 for R132H-; P < .001), less BOLD abnormality beyond the tumor
      margin (mean BOF, 0.255 +/- 0.03 for R132H+ and 0.728 +/- 0.04 for R132H-; P <
      .001), and less postoperative BOLD abnormality (residual fraction, 0.046 +/-
      0.0047 for R132H+ and 0.397 +/- 0.045 for R132H-; P < .001). Receiver operating
      characteristic curve analysis showed high sensitivity and specificity in the
      discrimination of R132H+ tumors from R132H- tumors with calculation of both Dice
      coefficient and BOF (area under the receiver operating characteristic curve,
      0.967 and 0.977, respectively). Conclusion R132H mutation status is an important
      variable affecting the extent of tumor-associated vascular dysregulation and the
      residual vascular dysregulation after surgical resection. (c) RSNA, 2018 Online
      supplemental material is available for this article.

PMID- 29369752
TI  - Fluorine MR Imaging Monitoring of Tumor Inflammation after High-Intensity Focused
      Ultrasound Ablation.
AB  - Purpose To investigate whether high-intensity focused ultrasound (HIFU)-induced
      macrophage infiltration could be longitudinally monitored with fluorine 19 (19F)
      magnetic resonance (MR) imaging in a quantitative manner. Materials and Methods
      BALB/c mice were subcutaneously inoculated with 4T1 cells and were separated into
      three groups: untreated mice (control, n = 9), HIFU-treated mice (HIFU, n = 9),
      and HIFU- and clodronate-treated mice (HIFU+Clod, n = 9). Immediately after HIFU
      treatment, all mice were intravenously given perfluorocarbon (PFC) emulsion. MR
      imaging examinations were performed 2, 4, 7, 10, and 14 days after HIFU
      treatment. Two-way repeated measures analysis of variance was used to analyze the
      changes in 19F signal over time and differences between groups. Histologic
      examinations were performed to confirm in vivo data. Results Fluorine 19 signals
      were detected at the rims of tumors and the peripheries of ablated lesions. Mean
      19F signal in tumors was significantly higher in HIFU-treated mice than in
      control mice up to day 4 (0.82 +/- 0.26 vs 0.42 +/- 0.17, P < .001). Fluorine 19
      signals were higher in the HIFU+Clod group than in the control group from day 4
      (0.82 +/- 0.23, P < .001) to day 14 (0.55 +/- 0.16 vs 0.28 +/- 0.06, P < .05).
      Histologic examination revealed macrophage infiltration around ablated lesions.
      Immunofluorescence staining confirmed PFC labeling of macrophages. Conclusion
      Fluorine 19 MR imaging can longitudinally capture and quantify HIFU-induced
      macrophage infiltration in preclinical tumor models. (c) RSNA, 2018 Online
      supplemental material is available for this article.

PMID- 29369753
TI  - The Incidental Splenic Mass at CT: Does It Need Further Work-up? An Observational
      Study.
AB  - Purpose To evaluate whether an incidentally noted splenic mass at abdominal
      computed tomography (CT) requires further imaging work-up. Materials and Methods
      In this institutional review board-approved HIPAA-compliant retrospective study,
      a search of a CT database was performed for patients with splenic masses at CT
      examinations of the abdomen and chest from 2002 to 2008. Patients were divided
      into three groups: group 1, patients with a history of malignancy; group 2,
      patients with symptoms such as weight loss, fever, or pain related to the left
      upper quadrant and epigastrium; and group 3, patients with incidental findings.
      Patients' CT scans, follow-up examinations, and electronic medical records were
      reviewed. Final diagnoses of the causes of the masses were confirmed with imaging
      follow-up (83.9%), clinical follow-up (13.7%), and pathologic examination (2.4%).
      Results This study included 379 patients, 214 (56.5%) women and 165 (43.5%) men,
      with a mean age +/- standard deviation of 59.3 years +/- 15.3 (range, 21-97
      years). There were 145 (38.3%) patients in the malignancy group, 29 (7.6%)
      patients in the symptomatic group, and 205 (54.1%) patients in the incidental
      group. The incidence of malignant splenic masses was 49 of 145 (33.8%) in the
      malignancy group, eight of 29 (27.6%) in the symptomatic group, and two of 205
      (1.0%) in the incidental group (P < .0001). The incidental group consisted of new
      diagnoses of lymphoma in one (50%) patient and metastases from ovarian carcinoma
      in one (50%) patient. Malignant splenic masses in the incidental group were not
      indeterminate, because synchronous tumors in other organs were diagnostic of
      malignancy. Conclusion In an incidental splenic mass, the likelihood of
      malignancy is very low (1.0%). Therefore, follow-up of incidental splenic masses
      may not be indicated. (c) RSNA, 2018.

PMID- 29369754
TI  - Bimodal Seasonality and Alternating Predominance of Norovirus GII.4 and Non
      GII.4, Hong Kong, China, 2014-20171.
AB  - We report emerging subtropical bimodal seasonality and alternating predominance
      of norovirus GII.4 and non-GII.4 genotypes in Hong Kong. GII.4 predominated in
      summer and autumn months and affected young children, whereas emergent non-GII.4
      genotypes predominated in winter months and affected all age groups. This highly
      dynamic epidemiology should inform vaccination strategies.

PMID- 29369755
TI  - Implementing Key Drivers for Diabetes Self-Management Education and Support
      Programs: Early Outcomes, Activities, Facilitators, and Barriers.

PMID- 29369756
TI  - Coordinated Approaches to Strengthen State and Local Public Health Actions to
      Prevent Obesity, Diabetes, and Heart Disease and Stroke.

PMID- 29369757
TI  - Telemedicine in the Management of Type 1 Diabetes.
AB  - BACKGROUND: Veterans with type 1 diabetes who live in rural Alabama and Georgia
      face barriers to receiving specialty diabetes care because of a lack of
      endocrinologists in the Central Alabama Veterans Health Care System. Telemedicine
      is a promising solution to help increase access to needed health care. We
      evaluated telemedicine's effectiveness in delivering endocrinology care from
      Atlanta-based endocrinologists. METHODS: We conducted a retrospective chart
      review of patients who were enrolled in the Atlanta VAMC Endocrinology Telehealth
      Clinic from June 2014 to October 2016. Outcomes of interest were hemoglobin A1c
      levels, changes in glycemic control, time savings for patients, cost savings for
      the US Veterans Health Administration, appointment adherence rates, and patient
      satisfaction with telehealth. RESULTS: Thirty-two patients with type 1 diabetes
      received telehealth care and in general received the recommended processes of
      diabetes care. Patients trended toward a decrease in mean hemoglobin A1c and
      glucose variability and a nonsignificant increase in hypoglycemic episodes.
      Patients saved 78 minutes of travel time (one way), and the VA saved $72.94 in
      travel reimbursements per patient visit. Patients adhered to 88% of scheduled
      telehealth appointments on average, and 100% of surveyed patients stated they
      would recommend telehealth to other veterans. CONCLUSIONS: Specialty diabetes
      care delivered via telemedicine was safe and was associated with time savings,
      cost savings, high appointment adherence rates, and high patient satisfaction.
      Our findings support growing evidence that telemedicine is an effective
      alternative method of health care delivery.

PMID- 29369758
TI  - Identifying Financially Sustainable Pricing Interventions to Promote Healthier
      Beverage Purchases in Small Neighborhood Stores.
AB  - INTRODUCTION: Residents of low-income communities often purchase sugar-sweetened
      beverages (SSBs) at small, neighborhood "corner" stores. Lowering water prices
      and increasing SSB prices are potentially complementary public health strategies
      to promote more healthful beverage purchasing patterns in these stores.
      Sustainability, however, depends on financial feasibility. Because in-store
      pricing experiments are complex and require retailers to take business risks, we
      used a simulation approach to identify profitable pricing combinations for corner
      stores. METHODS: The analytic approach was based on inventory models, which are
      suitable for modeling business operations. We used discrete-event simulation to
      build inventory models that use data representing beverage inventory, wholesale
      costs, changes in retail prices, and consumer demand for 2 corner stores in
      Baltimore, Maryland. Model outputs yielded ranges for water and SSB prices that
      increased water demand without loss of profit from combined water and SSB sales.
      RESULTS: A 20% SSB price increase allowed lowering water prices by up to 20%
      while maintaining profit and increased water demand by 9% and 14%, for stores
      selling SSBs in 12-oz cans and 16- to 20-oz bottles, respectively. Without
      changing water prices, profits could increase by 4% and 6%, respectively.
      Sensitivity analysis showed that stores with a higher volume of SSB sales could
      reduce water prices the most without loss of profit. CONCLUSION: Various
      combinations of SSB and water prices could encourage water consumption while
      maintaining or increasing store owners' profits. This model is a first step in
      designing and implementing profitable pricing strategies in collaboration with
      store owners.

PMID- 29369759
TI  - Sub-County Life Expectancy: A Tool to Improve Community Health and Advance Health
      Equity.
AB  - Compared with people in other developed countries, Americans live shorter lives,
      have more disease and disability, and lag on most population health measures.
      Recent research suggests that this poor comparative performance is primarily
      driven by profound local place-based disparities. Several initiatives
      successfully used sub-county life expectancy estimates to identify geographic
      disparities, generate widespread interest, and catalyze multisector actions. To
      explore the feasibility of scaling these efforts, the Centers for Disease Control
      and Prevention and the Council of State and Territorial Epidemiologists initiated
      a multiphase project - the Sub-County Assessment of Life Expectancy. Phase I
      participants reviewed the literature, assessed and identified appropriate tools,
      calculated locally relevant estimates, and developed methodological guidance.
      Phase I results suggest that most state and local health departments will be able
      to calculate actionable sub-county life expectancy estimates despite varying
      resources, expertise, and population sizes, densities, and geographies. To
      accelerate widespread scaling, we describe several successful case examples,
      identify user-friendly validated tools, and provide practical tips that resulted
      from lessons learned.

PMID- 29369760
TI  - Parity Could Use Some Fixing, But at Least It Won't Be Dismantled.
AB  - Nonquantitative treatment limitations may be why care for mental health and
      substance abuse disorders isn't keeping up with coverage gains.

PMID- 29369761
TI  - Is CAR-T Really Putting Us On Road to Gene Therapy?
AB  - Some say gene editing platforms like CRISPR are a truer version of gene therapy
      because they are designed to home in on a particular genomic location.

PMID- 29369762
TI  - Optum's Lisa Tseng Keep Entrepreneurial Ball Rolling.
AB  - The 37-year-old has a title: executive vice president of Optum. But she wears
      many hats, including running a division that sells affordable hearing aids.

PMID- 29369763
TI  - Underused Weapon In the War on Addiction.
AB  - Buprenorphine could save thousands more lives than it does-if it weren't for
      legal barriers, a fear of disruptive patients, and insurance red tape. And it can
      be prescribed in the primary care physician's office.

PMID- 29369764
TI  - The Show-me State Shows the Way On 'Health Homes' for Mental Health.
AB  - The medical home model for delivering health care is getting tested for people
      with mental health problems. Missouri has been a pacesetter.

PMID- 29369765
TI  - Shrinking the Psychiatrist Shortage.
AB  - Demand for mental health services outstrips the supply of psychiatrists.
      Aggravating the situation: Many psychiatrists don't take insurance. Nurse
      practitioners and physician assistants are beginning to fill the gap.

PMID- 29369766
TI  - Q&A: A Conversation with Patrick J. Kennedy. Parity Advocate Sees More Talk Than
      Action.
AB  - Insurers are playing "small ball" and not showing leadership, says the former
      congressman. And some "spin-dry" inpatient providers are doing more harm than
      good in combating the opioid epidemic. Meanwhile, Kennedy, who chronicled his own
      harrowing mental health and addiction struggles in a 2015 memoir, says he has
      been sober for more than six years.

PMID- 29369767
TI  - Viewpoint: Stop Fooling Around Re: Population Health.

PMID- 29369768
TI  - Biosimilars for Rheumatoid Arthritis: Don't Count Them Out Quite Yet.
AB  - Because physicians and health plan members both value choice, the current weak
      market for Inflectra and Renflexis could be a passing phase.

PMID- 29369769
TI  - Who Pays To Care for the Seriously Ill? Maybe It's Insurance Companies.
AB  - Palliative care would fill a need and could save health care dollars in the
      process. But providers often need to patch together CPT codes to get paid for it.

PMID- 29369770
TI  - Two New Drugs for Tardive Dyskinesia Hit the Market.
AB  - Ingrezza and Austedo were approved last year. ICER calculations raise questions
      about their price.

PMID- 29369771
TI  - Interoperability of Electronic Health Records: A Physician-Driven Redesign.
AB  - PURPOSE: Electronic health records (EHRs), now used by hundreds of thousands of
      providers and encouraged by federal policy, have the potential to improve quality
      and decrease costs in health care. But interoperability, although technically
      feasible among different EHR systems, is the weak link in the chain of logic.
      Interoperability is inhibited by poor understanding, by suboptimal
      implementation, and at times by a disinclination to dilute market share or
      patient base on the part of vendors or providers, respectively. The intent of
      this project has been to develop a series of practicable recommendations that, if
      followed by EHR vendors and users, can promote and enhance interoperability,
      helping EHRs reach their potential. METHODOLOGY: A group of 11 physicians, one
      nurse, and one health policy consultant, practicing from California to
      Massachusetts, has developed a document titled "Feature and Function
      Recommendations To Optimize Clinician Usability of Direct Interoperability To
      Enhance Patient Care" that offers recommendations from the clinician point of
      view. This report introduces some of these recommendations and suggests their
      implications for policy and the "virtualization" of EHRs.CONCLUSION: Widespread
      adoption of even a few of these recommendations by designers and vendors would
      enable a major advance toward the "Triple Aim" of improving the patient
      experience, improving the health of populations, and reducing per capita costs.

PMID- 29369772
TI  - Polymorphisms in folate metabolism genes are associated with susceptibility to
      presbycusis.
AB  - AIM: Presbycusis or age related hearing loss is caused by several extrinsic and
      intrinsic factors that damage the auditory system. Gene polymorphisms in folate
      metabolism were found to play an important role in the etiology of presbycusis.
      The present study aimed to investigate the role of 5,10-methylenetetrahydrofolate
      reductase (MTHFR), methionine synthase (MTR) and thymidylate synthase (TYMS) gene
      polymorphisms in the onset of presbycusis in a South Indian population. MAIN
      METHODS: A total of 220 subjects confirmed with presbycusis along with 270 age
      and sex matched healthy controls visiting MAA ENT Hospitals, Hyderabad, India
      were enrolled for the study. Genotyping of MTHFR C677T (rs180133) and A1298C
      (rs1801131), MTR A2756G (rs1805087), TSER (rs1801136) and TS1494indel6 bp
      (rs16430) was carried out using PCR & PCR-RFLP methods. KEY FINDINGS: The 'TT'
      genotype of MTHFR C677T and '152 bp/152 bp' genotype of TS1494indel6 bp showed
      statistically significant risk for presbycusis while CC genotype of MTHFR A1298C,
      '2R/2R' genotype of TSER at 3'UTR and 6 bp ins/6 bp ins of TYMS at 5'UTR were
      found to be protective. The T-A-A haplotype combination of MTHFR C677T, MTHFR
      A1298C and MTR A2756G as well as 3R- 152 bp of TYMS at 5'UTR and 3'UTR were also
      found to contribute significant risk for the onset of presbycusis. Further, the
      combination of SNP loci TSER: TS1494indel6 bp exhibited moderate linkage in
      presbycusis. SIGNIFICANCE: The present pilot study identified the significant
      association of gene variants of MTHFR and TYMS with presbycusis. These findings
      aid in early diagnosis of hearing loss in the elderly population.

PMID- 29369773
TI  - The Reticulum-Associated Protein RTN1A Specifically Identifies Human Dendritic
      Cells.
AB  - RTN1 is an endoplasmic reticulum-associated protein that was initially identified
      in neuronal tissues. Here we show that the main isoform RTN1A is a marker for
      dendritic cells. In the skin, HLA-DR+CD1ahighCD207+CD11cweak Langerhans cells
      were the only cells in the epidermis, and HLA-DR+CD11c+ dendritic cells were the
      main cells in the dermis, expressing this protein. RTN1A+ dendritic cells were
      also found in gingiva, trachea, tonsil, thymus, and peripheral blood. During
      differentiation of MUTZ-3 cells into Langerhans cells, expression of RTN1A mRNA
      and protein preceded established Langerhans cell markers CD1a and CD207, and
      RTN1A protein partially co-localized with the endoplasmic reticulum marker
      protein disulfide isomerase. In line with this observation, we found that RTN1A
      was expressed by around 80% of Langerhans cell precursors in human embryonic
      skin. Our findings show that RTN1A is a marker for cells of the dendritic
      lineage, including Langerhans cells and dermal dendritic cells. This unexpected
      finding will serve as a starting point for the elucidation of the, until now,
      elusive functional roles of RTN1A in both the immune and the nervous system.

PMID- 29369774
TI  - Cyclosporine for Epidermal Necrolysis: Absence of Beneficial Effect in a
      Retrospective Cohort of 174 Patients-Exposed/Unexposed and Propensity Score
      Matched Analyses.
AB  - Cyclosporine has shown promising results for mortality in patients with Stevens
      Johnson syndrome/toxic epidermal necrolysis. However, available studies included
      only a small number of patients and did not include a validated and homogenous
      control group. We present the results from a retrospective monocentric study
      including 174 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis
      during 2005-2016. Among them, 95 received cyclosporine (3 mg/kg/day) plus
      supportive care, and 79 received supportive care only. Both a traditional
      exposed/unexposed method and a propensity score-matching method were used to
      compare the progression of skin detachment between day 0 and day 5, the
      proportion of patients with cutaneous re-epithelialization starting on day 5 or
      mucosal re-epithelialization on day 10, the duration of progression, and the
      number of deaths between the two groups. None of these outcomes significantly
      favored cyclosporine, either by the exposed/unexposed method or the propensity
      score method. Acute renal failure affected more patients receiving cyclosporine
      (P = 0.05). Overall, the results of this epidemiological study did not show a
      beneficial effect of cyclosporine in patients with Stevens-Johnson syndrome/toxic
      epidermal necrolysis. They are discordant with those previously published. The
      large number of patients and the use of a propensity score method provide
      valuable insights. The main limitation of the study is the lack of randomization.

PMID- 29369775
TI  - Intestinal IFN-gamma-producing type 1 regulatory T cells coexpress CCR5 and
      programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of
      patients with inflammatory bowel disease.
AB  - BACKGROUND: IL-10 is an anti-inflammatory cytokine required for intestinal immune
      homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T
      (TR1) cells but is also produced by CD25+ regulatory T (Treg) cells. OBJECTIVE:
      We aimed to identify and characterize human intestinal TR1 cells and to
      investigate whether they are a relevant cellular source of IL-10 in patients with
      inflammatory bowel diseases (IBDs). METHODS: CD4+ T cells isolated from the
      intestinal lamina propria of human subjects and mice were analyzed for phenotype,
      cytokine production, and suppressive capacities. Intracellular IL-10 expression
      by CD4+ T-cell subsets in the inflamed guts of patients with IBD (Crohn disease
      or ulcerative colitis) was compared with that in cells from noninflamed control
      subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10
      expression were analyzed, and IL-1beta and IL-23 responsiveness was assessed.
      RESULTS: Intestinal TR1 cells could be identified by coexpression of CCR5 and
      programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5+PD-1+ TR1
      cells expressed IFN-gamma and efficiently suppressed T-cell proliferation and
      transfer colitis. Intestinal IFN-gamma+ TR1 cells, but not IL-7 receptor-positive
      TH cells or CD25+ Treg cells, showed lower IL-10 expression in patients with
      IBDs. TR1 cells were responsive to IL-23, and IFN-gamma+ TR1 cells downregulated
      IL-10 with IL-1beta and IL-23. Conversely, CD25+ Treg cells expressed higher
      levels of IL-1 receptor but showed stable IL-10 expression. CONCLUSIONS: We
      provide the first ex vivo characterization of human intestinal TR1 cells.
      Selective downregulation of IL-10 by IFN-gamma+ TR1 cells in response to
      proinflammatory cytokines is likely to drive excessive intestinal inflammation in
      patients with IBDs.

PMID- 29369776
TI  - Successful treatment of Marburg virus with orally administrated T-705
      (Favipiravir) in a mouse model.
AB  - Filoviruses, such as Marburg and Ebola viruses, cause severe disease in humans
      with high case fatality rates and are therefore considered biological threat
      agents. To date, no licensed vaccine or therapeutic exists for their treatment. T
      705 (favipiravir) is a pyrazinecarboxamide derivative that has shown broad
      antiviral activity against a number of viruses and is clinically licenced in
      Japan to treat influenza. Here we report the efficacy of T-705 against Marburg
      virus infection in vitro and in vivo. Notably, oral administration of T-705
      beginning one or two days post-infection and continuing for eight days resulted
      in complete survival of mice that had been intraperitoneally infected with mouse
      adapted Marburg virus (variant Angola). Moreover, lower doses of T-705 and higher
      doses administered later during infection (day 3 or 4 post-infection) showed
      partial efficacy, with at least half the infected mice surviving. Accordingly, we
      observed reductions in infectious virus particles and virus RNA levels following
      drug treatment that appeared to correlate with survival. Our findings suggest
      that T-705 may be an effective therapeutic against Marburg virus and might be
      especially promising for use in the event of an outbreak, where it could be
      orally administered quickly and safely even after exposure.

PMID- 29369777
TI  - Hippocampal astrocyte atrophy in a mouse depression model induced by
      corticosterone is reversed by fluoxetine instead of benzodiazepine diazepam.
AB  - Astrocytes have become promising new agents against major depressive disorders
      (MDD) primarily due to the crucial role they play in the pathogenesis of such
      disorders. However, a simple and reliable animal model that can be used to screen
      for astrocyte-targeting antidepressants has not yet been developed. In this
      study, we utilized a repeated corticosterone (CORT) injection paradigm to develop
      a mouse depression model wherein we examined the occurrence of alterations in
      hippocampal astrocyte population by using two astrocytic markers, namely, glial
      fibrillary acidic protein (GFAP) and S100beta. Moreover, we determined the
      effects of fluoxetine and diazepam on CORT-induced astrocytic alterations to
      assess the predictive validity. Results showed that repeated CORT injections
      showed no effects on the number of GFAP+ and S100beta+ astrocytes, but they
      decreased the protrusion length of GFAP+ astrocytes and GFAP protein expression
      in the hippocampus. Furthermore, repeated CORT injections produced a sustained
      increase of S100beta protein levels in the entire hippocampus of male mice. CORT
      induced hippocampal astrocyte disruption was antagonized by chronic fluoxetine
      treatment. By contrast, the anxiolytic drug diazepam was ineffective in the same
      experimental setting. All these findings suggest that the repeated CORT injection
      paradigm produces the astrocytic alterations similar to those in MDD and can
      serve as a useful mouse model to screen antidepressants meant to target
      astrocytes. These observations can also help in further discussing the underlying
      mechanisms of CORT-induced astrocytic alterations.

PMID- 29369778
TI  - Reinterpreting polarity and cancer: The changing landscape from tumor suppression
      to tumor promotion.
AB  - Cell polarity is a fundamental property used to generate asymmetry and structure
      in all cells. Cancer is associated with loss of cell and tissue structure. While
      observations made in model system such as Drosophila, identify polarity
      regulators as tumor suppressors that cause inappropriate cell division, studies
      in mammalian epithelia do not always support such a causative contribution. Our
      analysis of published cancer dataset shows that many polarity genes, including
      PARD6B, SCRIB, PRKCI, DLG1, DLG2, DLG5 and LLGL2, are frequently amplified in
      multiple cancers raising the possibility that mammalian epithelia may have
      evolved to use polarity proteins in multiple ways where they may have tumor
      promoting functions. In this review, we reinterpret the published results and
      propose a modified perspective for the role of polarity regulators in cancer
      biology. In addition to the traditional form of cell polarity, which is involved
      establishment of maintenance of normal cell structure and asymmetry, we propose
      that some mammalian polarity proteins also regulate subcellular polarity
      (intracellular asymmetry), which can improve cellular fitness to carry out
      functions such as proliferation, apoptosis, stress adaptation, stemness and
      organelle biology. Here, we define subcellular polarity and discuss evidence that
      supports a role for subcellular polarity in biology.

PMID- 29369780
TI  - Cell-specific and pH-sensitive nanostructure hydrogel based on chitosan as a
      photosensitizer carrier for selective photodynamic therapy.
AB  - The major problems of porphyrins as promising materials for photodynamic therapy
      (PDT) are their low solubility, subsequently aggregation in biological
      environments, and a lack of tumor selectivity. With this in mind, a chitosan
      based hydrogel conjugated with tetrakis(4-aminophenyl)porphyrin (NH2-TPP) and
      2,4,6-tris(p-formylphenoxy)-1,3,5-triazine (TRIPOD) via Schiff base linkage,
      functionalized with folate was designed and synthesized as a pH-sensitive, self
      healable and injectable targeted PS delivery system. This new hydrogel was
      characterized by FT-IR, 1H NMR, SEM, UV-vis, fluorescence spectroscopy and zeta
      potential. Formation of imine bonds with the aldehyde group of TRIPOD and amine
      group of NH2-TPP and chitosan, as a dynamic connection, was approved by
      rheological analysis. Spectroscopic characterizations revealed that aggregation
      of porphyrin in aqueous media was eliminated due to diminished pi stacking
      interaction of porphyrin in 3D cross-linked hydrogel structure. Hydrogel 3D
      microporous structure efficiently transfers the excitation energy to the
      porphyrin unit, yielding improvement singlet oxygen releases. Cytotoxicity and
      phototoxicity analysis of the CS/NH2-TPP/FA hydrogels indicating an excellent
      capability to kill cancer cells selectively and prevent damage to normal cells.
      This work presents a new and efficient model for the preparation of highly
      efficient and targeting photosensitizer delivery system.

PMID- 29369781
TI  - Incorporation of gelatin microparticles on the formation of adipose-derived stem
      cell spheroids.
AB  - The three-dimensional (3D) cell culture method provides a physiological
      environment that is similar to the in vivo conditions. The spheroid culture
      method is a 3D cell-culture approach that facilitates aggregation and interaction
      of cells with other adjacent cells to establish a microenvironment in vitro. In
      this study, gelatin microparticles (GMPs) were introduced into spheroids to
      enhance stem cell proliferation and viability. GMPs with different sizes and
      numbers were prepared to investigate their corresponding effects on cell
      proliferation. To investigate the effect of surface charge on the properties of
      spheroids, positively and negatively charged GMPs were also prepared by
      conjugating poly-amino acids on the surfaces of the GMPs. GMPs were successfully
      incorporated into adipose-derived stem cells (ASCs) to form spheroids. The
      results revealed no cytotoxicity in all treatment groups. Spheroids combined with
      GMPs showed higher proliferation potential compared to cell spheroids alone,
      suggesting that GMP/cell spheroids can be used for efficient delivery of stem
      cells to defect sites without the need for surgery, thereby highlighting the
      potential use of GMP/cell spheroids for stem cell therapy.

PMID- 29369779
TI  - EphB4: A promising target for upper aerodigestive malignancies.
AB  - The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the
      largest family of receptor tyrosine kinases (RTKs) that include two major
      subclasses, EphA and EphB. They form an important cell communication system with
      critical and diverse roles in a variety of biological processes during embryonic
      development. However, dysregulation of the Eph/ephrin interactions is implicated
      in cancer contributing to tumour growth, metastasis, and angiogenesis. Here, we
      focus on EphB4 and review recent developments in elucidating its role in upper
      aerodigestive malignancies to include lung cancer, head and neck cancer, and
      mesothelioma. In particular, we summarize information regarding EphB4
      structure/function and role in disease pathobiology. We also review the data
      supporting EphB4 as a potential pharmacological and immunotherapy target and
      finally, progress in the development of new therapeutic strategies including
      small molecule inhibitors of its activity is discussed. The emerging picture
      suggests that EphB4 is a valuable and attractive therapeutic target for upper
      aerodigestive malignancies.

PMID- 29369782
TI  - Pharmacological inhibitory profile of TAK-828F, a potent and selective orally
      available RORgammat inverse agonist.
AB  - Retinoic acid-related orphan receptor gammat (RORgammat) is a key master
      regulator of the differentiation and activation of IL-17 producing CD4+ Th17,
      CD8+ Tc17 and IL-17/IFN-gamma co-producing cells (Th1/17 cells). These cells play
      critical roles in the pathogenesis of autoimmune diseases such as inflammatory
      bowel disease and multiple sclerosis. Thus, RORgammat is an attractive target for
      the treatment of these diseases. We discovered TAK-828F, an orally available
      potent and selective RORgammat inverse agonist. The inhibitory effect on the
      activation and differentiation of Th17 cells by TAK-828F was evaluated in mouse
      and human primary cells. TAK-828F inhibited IL-17 production from mouse
      splenocytes and human peripheral blood mononuclear cells dose-dependently at
      concentrations of 0.01-10 MUM without affecting the production of IFN-gamma.
      Additionally, TAK-828F strongly inhibited Th17, Tc17 and Th1/17 cells'
      differentiation from naive T cells and memory CD4+ T cells at 100 nM without
      affecting Th1 cells' differentiation. In addition, TAK-828F improved Th17/Treg
      cells' population ratio by inhibiting Th17 cells' differentiation and up
      regulating Treg cells. Furthermore, TAK-828F, at 100 nM, reduced the production
      of Th17-related cytokines (IL-17, IL-17F and IL-22) without affecting IFN-gamma
      production in whole blood. These results demonstrate that TAK-828F has the potent
      and selective inhibitory activity against RORgammat both in mouse and human
      cells. Additionally, oral administration of TAK-828F showed promising efficacy in
      naive T cell transfer mouse colitis model. TAK-828F may provide a novel
      therapeutic option to treat immune diseases by inhibiting Th17 and Th1/17 cells'
      differentiation and improving imbalance between Th17 and Treg cells.

PMID- 29369783
TI  - Equifinality in empirical studies of cultural transmission.
AB  - Cultural systems exhibit equifinal behavior - a single final state may be arrived
      at via different mechanisms and/or from different initial states. Potential for
      equifinality exists in all empirical studies of cultural transmission including
      controlled experiments, observational field research, and computational
      simulations. Acknowledging and anticipating the existence of equifinality is
      important in empirical studies of social learning and cultural evolution; it
      helps us understand the limitations of analytical approaches and can improve our
      ability to predict the dynamics of cultural transmission. Here, I illustrate and
      discuss examples of equifinality in studies of social learning, and how certain
      experimental designs might be prone to it. I then review examples of equifinality
      discussed in the social learning literature, namely the use of s-shaped diffusion
      curves to discern individual from social learning and operational definitions and
      analytical approaches used in studies of conformist transmission. While
      equifinality exists to some extent in all studies of social learning, I make
      suggestions for how to address instances of it, with an emphasis on using data
      simulation and methodological verification alongside modern statistical
      approaches that emphasize prediction and model comparison. In cases where
      evaluated learning mechanisms are equifinal due to non-methodological factors, I
      suggest that this is not always a problem if it helps us predict cultural change.
      In some cases, equifinal learning mechanisms might offer insight into how both
      individual learning, social learning strategies and other endogenous social
      factors might by important in structuring cultural dynamics and within- and
      between-group heterogeneity.

PMID- 29369784
TI  - Impacts of nectar robbing on the foraging ecology of a territorial hummingbird.
AB  - While the effects of nectar robbing on plants are relatively well-studied, its
      impacts from the perspective of the pollinators of robbed plants is not. Numerous
      studies do consider the impacts of robbing on pollinator visitation to robbed
      plants, but rarely do they focus on its scaled-up impacts on individual
      pollinator behavior. We used radio telemetry to track the spatial and behavioral
      responses of the territorial hummingbird Aglaeactis cupripennis to experimental
      nectar robbing over a period of several days. Simulated nectar robbing impacted
      foraging behavior by increasing territory area, distance flown, and reliance on
      novel food resources, especially small-bodied flying insects. We did not observe
      any impact on the amount of time individuals spent foraging, nor did we observe
      territory abandonment. These findings indicate that nectar robbing may impose a
      significant energetic cost on pollinators via increased flight distances and
      shifts towards potentially less profitable food resources, and demonstrate the
      importance of quantifying the indirect effects of nectar robbing on pollinators
      in addition to plants.

PMID- 29369785
TI  - Pregnane X receptor mediates sorafenib resistance in advanced hepatocellular
      carcinoma.
AB  - BACKGROUND: Kinase inhibitor sorafenib is the most widely used drug for advanced
      HCC clinical treatment nowadays. However, sorafenib administration is only
      effective for a small portion of HCC patients, and the majority develop sorafenib
      resistance during treatment. Thus, it is urgent to discover the endogenous
      mechanism and identify new pharmaceutical targets of sorafenib-resistance.
      METHODS: Pregnane X receptor (PXR) was detected by immunohistochemistry and
      quantitative PCR. GST-pull down and LC-MS/MS was used to detect the interaction
      of PXR and Sorafenib. To test the properties of HCC tumor growth and metastasis,
      in vivo tumor explant model, FACS, trans-well assay, cell-survival inhibitory
      assay and Western blot were performed. In terms of mechanistic study, additional
      assays such as ChIP and luciferase reporter gene assay were applied. RESULTS: In
      the present work, we found high PXR level in clinical specimens is related to the
      poor prognosis of Sorafenib treated patients. By the mechanistic studies, we show
      that sorafenib binds to PXR and activates PXR pathway, and by which HCC cells
      develop sorafenib-resistance via activating. Moreover, PXR overexpression helps
      HCC cells to persist to sorafenib treatment. CONCLUSION: This study reports the
      endogenous sorafenib-resistance mechanism in HCC cells, which offers an
      opportunity to design new therapeutic approaches for HCC treatment. GENERAL
      SIGNIFICANCE: PXR mediates sorafenib-resistance in HCC cells and targeting PXR
      can be a useful approach to facilitate HCC treatment.

PMID- 29369786
TI  - Differential expression of PIWIL2 in papillary thyroid cancers.
AB  - Thyroid cancer is the most common type of endocrine malignancy and a leading
      cause of death among endocrine organ-related cancers. Similar to other types of
      cancers, early diagnosis of thyroid cancer is important to increase the survival
      and treatment of this disease. Several immunohistochemical markers are used in
      the differential diagnosis of thyroid papillary carcinoma. Also, increasing
      evidence indicates that P-element induced wimpy testis like 2 (PIWIL2) is an RNA
      binding protein involved in the induction and progression of numerous types of
      human malignancies such as lung, breast, colon, prostate and cervix cancers.
      However, the role of PIWIL2 was poorly investigated in thyroid cancers.
      Accordingly, aim of the present study was to elucidate the relationship between
      PIWIL2 and thyroid cancers. The expression level of PIWIL2 was determined by
      analyzing both protein and mRNA levels in papillary and micropapillary carcinoma
      tissues by using immunohistochemistry and real-time PCR methods, respectively.
      Immunohistochemical analysis of HBME-1, galectin-3 and CK-19 was also performed.
      Similar to other immune markers of HBME-1, galectin-3 and CK-19, protein
      expression levels of PIWIL2 was significantly up-regulated in both papillary and
      micropapillary thyroid cancers (p < 0.01). Moreover, consistent with protein
      expression levels, mRNA expression levels of PIWIL2 was elevated in both
      papillary and micropapillary thyroid cancer tissues. Yet, mRNA expression changes
      were statistically insignificant. In conclusion, results of the current study
      suggest that PIWIL2 can be involved in thyroid cancer tumorigenesis and can be
      used as a novel predictive biomarker and/or therapeutic target.

PMID- 29369787
TI  - The influence of peroxisome proliferator-activated receptor gamma (PPARgamma)
      ligands on cancer cell tumorigenicity.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) belongs to the
      nuclear receptor superfamily of PPARs (PPARalpha, PPARbeta/delta, PPARgamma).
      Numerous studies have concentrated on the key role of PPARs in inflammation and a
      variety of cancers which include prostate, breast, glioblastoma, neuroblastoma,
      pancreatic, hepatic, leukemia, and bladder and thyroid tumors. This review,
      specifically deals with anti-tumor and tumorigenicity effects of PPARgamma and
      its natural and synthetic agonists including Troglitazone, Cladosporol A, B, 15
      Deoxi-Delta12-14-Prostaglondin J2 (15-d-PGJ2), Ciglitazon, docosahexaenoic acid,
      eicosapentaenoic acid Alpha-eleostreac acid, Amorfrutin C, Sphingosine 1
      phosphate, Evodiamine, Excavatolide B vs respected antagonists as GW9662,
      bisphenol-A-diglycidyl-ether. Considering the contradictory role of PPARgamma on
      tumorigenicity, a number of studies demonstrate mechanisms involved in
      tumorigenicity effects of PPARgamma agonists while several studies suggest key
      roles of PPARgamma agonists in anti-proliferation, metastasis, angiogenesis,
      apoptosis and immunomodulatory through activation of signaling pathways in
      different cancer cells as well as in cancer stem cells. The aim of this review is
      summarizing of tumorigenicity and anti-tumorigenicity activities of PPARgamma
      agonists and antagonists as well as therapeutic activities of these reagents as a
      coadjutant drug in the treatment of different cancers.

PMID- 29369788
TI  - Behavior of pyrophite shrubs in mediterranean terrestrial ecosystems (i):
      Population and reproductive model.
AB  - The mathematical submodel ULEX is used to study the dynamic behavior of the
      green, floral and woody biomass of the main pyrophite shrub species, the gorse
      (Ulex parviflorus Pourret), and its relationship with other shrub species,
      typical of a Mediterranean ecosystem. The focus are the ecological conditions of
      post-fire stage growth, and its efficacy as a protective cover against erosion
      processes in the short, medium and long term, both in normal conditions and at
      the limits of desertification conditions. The model sets a target to observe the
      behavior and to anticipate and consequently intervene with adequate protection,
      restoration and management measures.

PMID- 29369789
TI  - Autoimmunity and cardiac arrhythmias in endemic pemphigus foliaceus-Association,
      correlation, or causation?

PMID- 29369790
TI  - Homeostatic interplay between FoxO proteins and ER proteostasis in cancer and
      other diseases.
AB  - Cancer cells are exposed to adverse conditions within the tumor microenvironment
      that challenge cells to adapt and survive. Several of these homeostatic
      perturbations insults alter the normal function of the endoplasmic reticulum
      (ER), resulting in the accumulation of misfolded proteins. ER stress triggers a
      conserved signaling pathway known as the unfolded protein response (UPR) to cope
      with the stress or trigger apoptosis of damaged cells. The UPR has been described
      as a major driver in the acquisition of malignant characteristics that ultimately
      lead to cancer progression. Although, several reports describe the relevance of
      the UPR in tumor growth, the possible crosstalk with other cancer-related
      pathways is starting to be elucidated. The Forkhead Box O (FoxO) subfamily of
      proteins has a major role in cancer progression, where chromosomal translocations
      and deregulated signaling lead to loss-of-function of FoxO proteins, contributing
      to tumor progression. Here we discuss the homeostatic connection between the UPR
      and FoxO proteins and its possible implications to tumor progression and the
      acquisition of several hallmarks of cancer. In addition, studies linking a
      crosstalk between the UPR and FoxO proteins in other diseases, including
      neurodegeneration and metabolic disorders is provided.

PMID- 29369791
TI  - Aging exacerbates cognitive and anxiety alterations induced by an
      intracerebroventricular injection of amyloid-beta1-42 peptide in mice.
AB  - An increasing body of evidence indicates that the activation of indoleamine-2,3
      dyoxigenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN)
      pathway, is involved in Abeta1-42-neurotoxicity and AD pathogenesis. We have
      reported for the first time that brain IDO activation is related to Abeta1-42
      exposure in young mice. Because aging is characterized by a brain dyshomeostasis
      and because it remains the most dominant risk factor for AD, the purpose of this
      study was to determine whether aging is associated with a higher sensitivity to
      behavioural and neurochemical alterations elicited by an intracerebroventricular
      (i.c.v.) injection of Abeta1-42 (400 pmol/mice), and whether KYN pathway is
      involved in these effects. We confirmed that aged mice displayed higher cognitive
      deficit in the object recognition test and higher anxiety-like behaviour in the
      elevated plus-maze and open field tests after the Abeta1-42 administration. Aged
      mice also responded to Abeta1-42 with a higher deficiency of brain-derived
      neurotrophic factor, glutathione levels and total radical-trapping antioxidant
      capacity, a higher IDO activity, and a higher KYN and KYN/tryptophan ratio in the
      prefrontal cortex and hippocampus. These effects of Abeta1-42 were associated
      with a higher proinflammatory status, as measured by higher levels of interleukin
      6, lower levels of interleukin-10 and higher expression of glial fibrillary
      acidic protein (GFAP) and allograft inflammatory factor 1 (Iba1) in the brain of
      aged mice. These results represent primary evidence suggesting that age
      associated inflammatory signature and down-regulation of neuroprotectants in the
      brain render aged mice more vulnerable to Abeta1-42-induced memory loss, anxiety
      symptoms and KYN pathway dysregulation.

PMID- 29369792
TI  - Hematology from embryo to adult in the bobwhite quail (Colinus virginianus):
      Differential effects in the adult of clutch, sex and hypoxic incubation.
AB  - Hematology and its regulation in developing birds have been primarily
      investigated in response to relatively short-term environmental challenges in the
      embryo. Yet, whether any changes induced in the embryo persist into adulthood as
      a hematological form of "fetal programming" is unknown. We hypothesized that: 1)
      chronic as opposed to acute hypoxic incubation will alter hematological
      respiratory variables in embryos of bobwhite quail (Colinus virginianus), and 2)
      alterations first appearing in the embryo will persist into hatchlings through
      into adulthood. To test these hypotheses, we first developed an embryo-to-adult
      profile of normal hematological development by measuring hematocrit (Hct), red
      blood cell concentration ([RBC]), hemoglobin concentration ([Hb]), mean
      corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin
      concentration, as well plasma osmolality. Hct, [RBC] and [Hb] in normoxic
      incubated birds (controls) steadily increased from ~22%, ~1.6 * 106 MUL-1 and ~7
      g% in day 12 embryos to almost double the values at maturity in adult birds. Both
      cohort and sex affected hematology of normoxic-incubated birds. A second
      population, incubated from day 0 (d0) in 15% O2, surprisingly revealed little or
      no significant difference from controls in hematology in embryos. In hatchlings
      and adults, hypoxic incubation caused no significant modification to any
      variables. Compared to major hematological effects caused by hypoxic incubation
      in chickens, the hematology of the bobwhite quail embryo appears to be minimally
      affected by hypoxic incubation, with very few effects induced during hypoxic
      incubation actually persisting into adulthood.

PMID- 29369794
TI  - Epigenetics in teleost fish: From molecular mechanisms to physiological
      phenotypes.
AB  - While the field of epigenetics is increasingly recognized to contribute to the
      emergence of phenotypes in mammalian research models across different
      developmental and generational timescales, the comparative biology of epigenetics
      in the large and physiologically diverse vertebrate infraclass of teleost fish
      remains comparatively understudied. The cypriniform zebrafish and the salmoniform
      rainbow trout and Atlantic salmon represent two especially important teleost
      orders, because they offer the unique possibility to comparatively investigate
      the role of epigenetic regulation in 3R and 4R duplicated genomes. In addition to
      their sequenced genomes, these teleost species are well-characterized model
      species for development and physiology, and therefore allow for an investigation
      of the role of epigenetic modifications in the emergence of physiological
      phenotypes during an organism's lifespan and in subsequent generations. This
      review aims firstly to describe the evolution of the repertoire of genes involved
      in key molecular epigenetic pathways including histone modifications, DNA
      methylation and microRNAs in zebrafish, rainbow trout, and Atlantic salmon, and
      secondly, to discuss recent advances in research highlighting a role for
      molecular epigenetics in shaping physiological phenotypes in these and other
      teleost models. Finally, by discussing themes and current limitations of the
      emerging field of teleost epigenetics from both theoretical and technical points
      of view, we will highlight future research needs and discuss how epigenetics will
      not only help address basic research questions in comparative teleost physiology,
      but also inform translational research including aquaculture, aquatic toxicology,
      and human disease.

PMID- 29369793
TI  - Alpha galactosidase A activity in Parkinson's disease.
AB  - Glucocerebrosidase (GCase, deficient in Gaucher disease) enzymatic activity
      measured in dried blood spots of Parkinson's Disease (PD) cases is within healthy
      range but reduced compared to controls. It is not known whether activities of
      additional lysosomal enzymes are reduced in dried blood spots in PD. To test
      whether reduction in lysosomal enzymatic activity in PD is specific to GCase, we
      measured GCase, acid sphingomyelinase (deficient in Niemann-Pick disease types A
      and B), alpha galactosidase A (deficient in Fabry), acid alpha-glucosidase
      (deficient in Pompe) and galactosylceramidase (deficient in Krabbe) enzymatic
      activities in dried blood spots of PD patients (n = 648) and controls (n = 317)
      recruited from Columbia University. Full sequencing of glucocerebrosidase (GBA)
      and the LRRK2 G2019S mutation was performed. Enzymatic activities were compared
      between PD cases and controls using t-test and regression models adjusted for
      age, gender, and GBA and LRRK2 G2019S mutation status. Alpha galactosidase A
      activity was lower in PD cases compared to controls both when only non-carriers
      were included (excluding all GBA and LRRK2 G2019S carriers and PD cases with age
      at-onset below 40) [2.85 MUmol/l/h versus 3.12 MUmol/l/h, p = 0.018; after
      controlling for batch effect, p = 0.006 (468 PD cases and 296 controls)], and
      when including the entire cohort (2.89 MUmol/l/h versus 3.10 MUmol/l/h, p =
      0.040; after controlling for batch effect, p = 0.011). Because the alpha
      galactosidase A gene is X-linked, we stratified the analyses by sex. Among women
      who were non-carriers of GBA and LRRK2 G2019S mutations (PD, n = 155; control, n
      = 194), alpha galactosidase A activity was lower in PD compared to controls (2.77
      MUmol/l/h versus 3.10 MUmol/l/h, p = 0.044; after controlling for a batch effect,
      p = 0.001). The enzymatic activity of acid sphingomyelinase, acid alpha
      glucosidase and galactosylceramidase was not significantly different between PD
      and controls. In non-carriers, most lysosomal enzyme activities were correlated,
      with the strongest association in GCase, acid alpha-glucosidase, and alpha
      galactosidase A (Pearson correlation coefficient between 0.382 and 0.532). In a
      regression model with all five enzymes among non-carriers (adjusted for sex and
      age), higher alpha galactosidase A activity was associated with lower odds of PD
      status (OR = 0.54; 95% CI:0.31-0.95; p = 0.032). When LRRK2 G2019S PD carriers (n
      = 37) were compared to non-carriers with PD, carriers had higher GCase, acid
      sphingomyelinase and alpha galactosidase A activity. We conclude that alpha
      galactosidase A may have a potential independent role in PD, in addition to
      GCase.

PMID- 29369795
TI  - Cardiovascular magnetic resonance characterization of myocardial and vascular
      function in rheumatoid arthritis patients.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a multisystem, autoimmune disorder and
      confers one of the strongest risks for cardiovascular disease (CVD) morbidity and
      mortality. OBJECTIVE: To assess myocardial function and vascular stiffness in RA
      patients with and without cardiovascular risk factors (CVRFs) using
      cardiovascular magnetic resonance (CMR). METHODS: Twenty-three RA patients with
      no CVRFs (17 female, mean age 52 +/- 13 years), 46 RA patients with CVRFs (32
      female, mean age 53 +/- 12), 50 normal controls (32 female, mean age 50 +/- 11
      years), and 13 controls with CVRFs (7 female, mean age 55 +/- 7 years), underwent
      CMR at 1.5 Tesla, including evaluation of left ventricular (LV) ejection
      fraction, strain, and vascular elasticity (aortic distensibility [AD] and pulse
      wave velocity [PWV]). Disease activity and duration were recorded for each
      patient. Subjects with known symptomatic CVD were excluded. RESULTS: LV volumes,
      mass, and ejection fraction were similar in the four groups. RA patients with
      CVRFs showed the greatest abnormality in mid short-axis circumferential systolic
      strain, peak diastolic strain rate, and vascular indices. RA patients without
      CVRFs showed a similar degree of vascular dysfunction and deformational
      abnormality as controls with CVRFs. AD and total PWV correlated with myocardial
      strain and RA disease activity. On multivariate regression analysis, strain was
      related to age, RA disease activity, AD, and PWV. CONCLUSION: CMR demonstrates
      impaired myocardial deformation and vascular function in asymptomatic RA
      patients, worse in those with CVRFs. Subclinical cardiovascular abnormalities are
      frequent and appear to be incremental to those due to traditional CVRFs and
      likely contribute to the excess CVD in RA.

PMID- 29369796
TI  - Asiatic acid inhibits LPS-induced inflammatory response in endometrial epithelial
      cells.
AB  - Accumulating evidence indicates that asiatic acid, a natural triterpene isolated
      from Centella asiatica, has anti-inflammatory activity. However, the anti
      inflammatory effects of asiatic acid on LPS-stimulated endometrial epithelial
      cells and the involved molecular pathways have not been completely elucidated. In
      the present study, we evaluated the effects of asiatic acid on LPS-induced
      inflammatory response in endometrial epithelial cells. Mouse endometrial
      epithelial cells were treated with asiatic acid and stimulated with LPS. ELISA
      was performed to measure the levels of inflammatory cytokines TNF-alpha, IL
      1beta, and PGE2. Western blot analysis was used to test the expression of
      PPARgamma and NF-kappaB. The results showed that LPS-induced inflammatory
      mediators TNF-alpha, IL-1beta, NO, and PGE2 were significantly inhibited by
      asiatic acid. Furthermore, LPS-induced TLR4 expression and NF-kappaB activation
      were concentration-dependently suppressed by asiatic acid. In addition, asiatic
      acid was found to increase the expression of PPARgamma in a concentration
      dependently manner. The inhibition of asiatic acid on inflammatory mediators
      production were prevented by PPARgamma inhibitor, GW9662. Taken together, these
      results showed that asiatic acid exhibited its anti-inflammatory effects in
      endometrial epithelial cells by activating PPARgamma.

PMID- 29369797
TI  - Estimating summary statistics for electronic health record laboratory data for
      use in high-throughput phenotyping algorithms.
AB  - We study the question of how to represent or summarize raw laboratory data taken
      from an electronic health record (EHR) using parametric model selection to reduce
      or cope with biases induced through clinical care. It has been previously
      demonstrated that the health care process (Hripcsak and Albers, 2012, 2013), as
      defined by measurement context (Hripcsak and Albers, 2013; Albers et al., 2012)
      and measurement patterns (Albers and Hripcsak, 2010, 2012), can influence how EHR
      data are distributed statistically (Kohane and Weber, 2013; Pivovarov et al.,
      2014). We construct an algorithm, PopKLD, which is based on information criterion
      model selection (Burnham and Anderson, 2002; Claeskens and Hjort, 2008), is
      intended to reduce and cope with health care process biases and to produce an
      intuitively understandable continuous summary. The PopKLD algorithm can be
      automated and is designed to be applicable in high-throughput settings; for
      example, the output of the PopKLD algorithm can be used as input for phenotyping
      algorithms. Moreover, we develop the PopKLD-CAT algorithm that transforms the
      continuous PopKLD summary into a categorical summary useful for applications that
      require categorical data such as topic modeling. We evaluate our methodology in
      two ways. First, we apply the method to laboratory data collected in two
      different health care contexts, primary versus intensive care. We show that the
      PopKLD preserves known physiologic features in the data that are lost when
      summarizing the data using more common laboratory data summaries such as mean and
      standard deviation. Second, for three disease-laboratory measurement pairs, we
      perform a phenotyping task: we use the PopKLD and PopKLD-CAT algorithms to define
      high and low values of the laboratory variable that are used for defining a
      disease state. We then compare the relationship between the PopKLD-CAT summary
      disease predictions and the same predictions using empirically estimated mean and
      standard deviation to a gold standard generated by clinical review of patient
      records. We find that the PopKLD laboratory data summary is substantially better
      at predicting disease state. The PopKLD or PopKLD-CAT algorithms are not meant to
      be used as phenotyping algorithms, but we use the phenotyping task to show what
      information can be gained when using a more informative laboratory data summary.
      In the process of evaluation our method we show that the different clinical
      contexts and laboratory measurements necessitate different statistical summaries.
      Similarly, leveraging the principle of maximum entropy we argue that while some
      laboratory data only have sufficient information to estimate a mean and standard
      deviation, other laboratory data captured in an EHR contain substantially more
      information than can be captured in higher-parameter models.

PMID- 29369799
TI  - Bistability and phase variation in Salmonella enterica.
AB  - Cell-to-cell differences in bacterial gene expression can merely reflect the
      occurrence of noise. In certain cases, however, heterogeneous gene expression is
      a programmed event that results in bistable expression. If bistability is
      heritable, bacterial lineages are formed. When programmed bistability is
      reversible, the phenomenon is known as phase variation. In certain cases,
      bistability is controlled by genetic mechanisms (e. g., DNA rearrangement). In
      other cases, bistability has epigenetic origin. A robust epigenetic mechanism for
      the formation of bacterial lineages is the formation of heritable DNA methylation
      patterns. However, bistability can also arise upon propagation of gene expression
      patterns by feedback loops that are stable upon cell division. This review
      describes examples of bistability and phase variation in Salmonella enterica and
      discusses their adaptive value, sometimes in a speculative manner.

PMID- 29369798
TI  - Prognostic Role of BRAFV600E Cellular Localization in Melanoma.
AB  - BACKGROUND: Approximately half of cutaneous melanoma tissues harbor BRAFV600E
      mutations, resulting in a constitutive activation of the mitogen-activated
      protein kinase (MAPK) pathway. Nuclear-cytoplasmic transport machinery is
      dysregulated in neoplastic cells and alters the key regulatory proteins that can
      lead to tumor progression and drug resistance. The significance of nuclear
      localization of BRAFV600E has not been fully understood. We examined the clinical
      significance of intracellular localization of BRAFV600E in cutaneous melanoma.
      STUDY DESIGN: Immunohistochemical analysis of BRAFV600E was performed on formalin
      fixed, paraffin-embedded specimens of cutaneous melanoma (n = 91). Staining
      intensity was graded in a blinded manner. Correlations to clinical factors were
      analyzed by Fisher's exact test and 2-tailed t-test. Localization of BRAFV600E
      was determined in melanoma cells, and we investigated their resistance to
      BRAFV600E-specific inhibitor according to nuclear localization in both in vitro
      and in vivo models. RESULTS: We included 91 patients, of whom 32% (29 of 91) had
      cytoplasmic BRAFV600E. Nuclear BRAFV600E was observed in 30% (27 of 91). Overall,
      BRAFV600E expression correlated with TNM stage (p = 0.011), mitotic activity (p =
      0.010), and ulceration (p = 0.045). Nuclear BRAFV600E expression correlated with
      overall clinical stage (p < 0.001), tumor size (p < 0.001), regional lymph node
      (p < 0.017), depth of invasion (p = 0.005), Clark level (p < 0.001), mitotic
      activity (p < 0.001), ulceration (p < 0.001), and margin status (p = 0.017). On a
      cellular level, BRAFV600E was identified in the nucleus, and its translocation
      was serum dependent. Our in vitro and in vivo data revealed sequestration of
      BRAFV600E in the cytosol-sensitized resistant cells to vemurafenib; nuclear
      retention of BRAFV600E was associated with aggressiveness and drug resistance.
      CONCLUSIONS: Nuclear localization of BRAFV600E is associated with melanoma
      aggressiveness. Further multi-institutional studies are warranted to confirm the
      clinical relevance of nuclear localization of BRAFV600E.

PMID- 29369800
TI  - Prognostic Factors for Mortality among Day +100 Survivors after Allogeneic
      Hematopoietic Cell Transplantation.
AB  - Although day +100 survival among allogeneic hematopoietic cell transplantation
      (HCT) recipients has improved over time, longer-term survival remains a
      challenge. The aim of this study was to identify prognostic factors for survival
      among patients surviving longer than 100 days using baseline characteristics and
      factors identified within the first 100 days after transplantation. Of 413
      patients undergoing a first allogeneic HCT between 2006 and 2014, 335 survived
      >100 days post-transplantation. The majority underwent a myeloablative
      transplantation (75%) with a bone marrow (BM) (52%) graft source. One-year all
      cause mortality (ACM) was 29%, with 16% relapse mortality (RM) and 12% nonrelapse
      mortality. In multivariable analysis, high-risk disease (hazard ratio [HR], 1.55;
      P = .003), non-cytomegalovirus infection (HR, 1.79; P = .003), more days
      hospitalized (HR, 1.16; P < .001), and relapse (HR, 4.38; P < .001) within the
      first 100 days were associated with increased risk of ACM. Patients with higher
      income (HR, .89; P = .024) and those who received BM (HR, .52; P < .001) or
      umbilical cord blood (HR, .40; P = .002) relative to peripheral blood stem cells
      had lower risk of ACM. Our study identifies risk factors for adverse long-term
      survival in 100-day survivors, a time point when patients frequently are
      discharged from transplantation centers. In addition to disease- and
      transplantation-related factors, low socioeconomic status was associated with
      worse long-term survival, highlighting the need for focused efforts to improve
      outcomes in vulnerable patient populations.

PMID- 29369801
TI  - Prediction of human pharmacokinetics of activated recombinant factor VII and B
      domain truncated factor VIII from animal population pharmacokinetic models of
      haemophilia.
AB  - Various experimental animal models are used in haemophilia research, however,
      little is known about how well the different species predict pharmacokinetic (PK)
      profiles in haemophilia patients. The aim of the current study was to describe
      the plasma concentration-time profile of recombinant activated factor VII
      (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal
      models using population PK modelling, and apply a simulation-based approach to
      evaluate how well the developed animal population PK models predict human PK. PK
      models were developed for rFVIIa and rFVIII in mice, rats, monkeys, and dogs
      using nonlinear mixed-effects modelling, accounting for inter-individual
      variability, nonlinear kinetics and covariate effects. Three scaling principles
      were applied to predict human PK: proportional scaling to body weight from single
      species, scaling with fixed theory-based allometric exponents from single
      species, and allometric interspecies scaling with estimated allometric
      coefficients and exponents. The plasma concentration-time profile of rFVIIa and
      rFVIII in mice, rats, monkeys and dogs were accurately described by the developed
      species-specific PK models, accounting for nonlinear kinetics and gender-specific
      difference in clearance for rFVIII. The predictive performance of the animal
      population PK models of rFVIIa and rFVIII revealed significant species-variation.
      The developed PK models of rFVIIa and rFVIII in monkeys and dogs along with
      allometric interspecies scaling revealed high predictive performance for human
      PK, and may promote rational decision-making in future first-in-human trials for
      rFVIIa and rFVIII variants.

PMID- 29369802
TI  - Green, fast and cheap paper-based method for estimating equivalence ratio of
      cationic carriers to DNA in gene delivery formulations.
AB  - To achieve efficient and safe cationic carrier-mediated gene delivery for gene
      therapy, the optimal ratio of carrier to DNA in formulations is a key factor and
      it is usually determined prior to transfection experiments. In this work, a
      simplified drop-and-read assay was developed for the first time using paper as a
      platform to estimate the equivalence ratio of cationic carriers to negatively
      charged DNA. By spotting a series of complexes containing varied ratios of
      carrier to DNA on filter paper, then allowing them to dry and finally dropping
      yellowish-green anionic 2',7'-dichlorofluorescein dye solution on top of the
      complexes, the equivalence point was detectable by the instant formation of
      stable pink spots as a result of the dye adsorption onto the positively charged
      complexes and free carriers. The method gave the same results as those determined
      by gel retardation assay and zeta potential measurement, however it allowed more
      rapid reporting of results in 5 min and required no tedious steps, harmful
      reagents or expensive instruments. By using paper instead of microcentrifuge
      tubes and omitting centrifugation, plasticware and electrical energy were no
      longer consumed and disposal of this degradable material was more environmentally
      friendly. With respect to analytical performance, filter paper inherently holding
      negative charge helped to trap and concentrate the complexes on the white
      background, enabling greater visibility of the colored spots and a lower required
      amount of DNA used for the assay. The method was successfully applied to estimate
      the equivalence ratios in a variety of gene delivery formulations containing
      different types of cationic carriers, i.e. polymers, dendrimers, liposomes and
      niosomes.

PMID- 29369803
TI  - Inhibitory modulation of the cough reflex by acetylcholine in the caudal nucleus
      tractus solitarii of the rabbit.
AB  - A cholinergic system has been described in the nucleus tractus solitarii (NTS).
      However, no information is available on the role played by acetylcholine (ACh) in
      the modulation of the cough reflex within the caudal NTS that has an important
      function in cough regulation. We addressed this issue making use of bilateral
      microinjections (30-50 nl) of 10 mM ACh combined with 5 mM physostigmine as well
      as of 10 mM mecamylamine or 10 mM scopolamine into the caudal NTS of
      pentobarbital sodium-anesthetized, spontaneously breathing rabbits.
      Microinjections of ACh/physostigmine caused depressant effects on the cough
      reflex induced by mechanical and chemical stimulation of the tracheobronchial
      tree. They also elicited transient increases in respiratory frequency and
      decreases in abdominal activity. These effects were prevented by scopolamine, but
      not by mecamylamine. The results show for the first time that ACh exerts an
      inhibitory modulation of the cough reflex through muscarinic receptors within the
      caudal NTS. They also may provide hints for novel antitussive approaches.

PMID- 29369805
TI  - Computational Analysis of Epidermal Growth Factor Receptor Mutations Predicts
      Differential Drug Sensitivity Profiles toward Kinase Inhibitors.
AB  - INTRODUCTION: A significant proportion of patients with lung cancer carry
      mutations in the EGFR kinase domain. The presence of a deletion mutation in exon
      19 or L858R point mutation in the EGFR kinase domain has been shown to cause
      enhanced efficacy of inhibitor treatment in patients with NSCLC. Several less
      frequent (uncommon) mutations in the EGFR kinase domain with potential
      implications in treatment response have also been reported. The role of a limited
      number of uncommon mutations in drug sensitivity was experimentally verified.
      However, a huge number of these mutations remain uncharacterized for inhibitor
      sensitivity or resistance. METHODS: A large-scale computational analysis of
      clinically reported 298 point mutants of EGFR kinase domain has been performed,
      and drug sensitivity profiles for each mutant toward seven kinase inhibitors has
      been determined by molecular docking. In addition, the relative inhibitor binding
      affinity toward each drug as compared with that of adenosine triphosphate was
      calculated for each mutant. RESULTS: The inhibitor sensitivity profiles predicted
      in this study for a set of previously characterized mutants correlated well with
      the published clinical, experimental, and computational data. Both the single and
      compound mutations displayed differential inhibitor sensitivity toward first- and
      next-generation kinase inhibitors. CONCLUSIONS: The present study provides
      predicted drug sensitivity profiles for a large panel of uncommon EGFR mutations
      toward multiple inhibitors, which may help clinicians in deciding mutant-specific
      treatment strategies.

PMID- 29369804
TI  - Knowledge of Inhaled Therapy and Responsibility for Asthma Management Among Young
      Teens With Uncontrolled Persistent Asthma.
AB  - OBJECTIVES: To compare the abilities of teens with uncontrolled persistent asthma
      and their caregivers to identify inhaled medications and state correct
      indications for use; examine medication responsibility within dyads; and
      determine whether responsibility is associated with knowledge about inhaled
      therapies. METHODS: In the baseline survey for the School-Based Asthma Care for
      Teens (SB-ACT) trial, we separately asked caregivers and teens to: 1) identify
      the teen's inhaled asthma therapies by name and from a picture chart (complete
      matches considered "concordant"); 2) describe indications of use for each
      medication; and 3) describe the allocation of responsibility for medication use
      within dyads. We limited analyses to dyads in which either member reported at
      least one rescue and one inhaled controller medication; we used McNemar and
      Pearson chi-square tests. RESULTS: A total of 136 dyads were analyzed. More
      caregivers than teens concordantly identified medications (63% vs 31%, P < .001).
      There was no difference between caregivers and teens in the ability to state
      correct indications for use (56% vs 54%, P = .79). More teens than caregivers
      endorsed "full teen responsibility" for rescue medication (65% vs 27%, P < .001)
      and controller medication use (50% vs 15%, P < .001). Neither concordant
      identification nor knowing indications for use was associated with reported
      medication responsibility. CONCLUSIONS: Medication responsibility within dyads of
      caregivers and teens with persistent asthma is not associated with knowledge
      about inhaled therapies. Targeting both members of the dyad with education and
      self-management strategies before responsibility transitions start may allow
      providers to avoid a missed opportunity to support these emerging stakeholders to
      adherence.

PMID- 29369806
TI  - Self-sensibilized polymeric prodrug co-delivering MMP-9 shRNA plasmid for
      combined treatment of tumors.
AB  - : Polymeric prodrugs are of immense interest as anticancer drug-delivery system
      owing to their superior drug stability during circulation and satisfactory drug
      loading capacity. However, they are usually less effective than free drugs due to
      imperfect degradable characteristics or active sites blockage. A polymeric
      prodrug (HPAA-MTX) with chemotherapeutic self-sensibilization effect consisting
      of glutathione (GSH)-triggered hyperbranched poly(amido amine) (HPAA) and
      methotrexate (MTX) was designed and synthesized in this work. This prodrug not
      only showed better inhibition effect on the tumor cells proliferation compared
      with free MTX, but also displayed selective sensibilization to tumor cells rather
      than normal cells. Meanwhile, HPAA-MTX was also explored as a MMP-9 shRNA plasmid
      delivery vector due to their rich amino group of HPAA, accompanying with MTX for
      simultaneous inhibiting tumor cells proliferation and migration. As expected,
      HPAA-MTX possessed excellent gene delivery capacity with significant down
      regulation expression of MMP-9 protein and further inhibition of MCF-7 cells
      migration. Benefiting from the self-sensibilization effect and MTX/MMP-9 co
      delivery strategy, this HPAA-MTX/MMP-9 co-delivery system exhibited significantly
      improved therapeutic efficacy to breast cancer in a combined manner which was
      confirmed through in vitro and in vivo assays. The strategy established in this
      study provided a facile "all-in-one" platform to integrate the drug/gene co
      delivery strategy and self-sensibilization effect into one single nanocomposite
      for potential cancer treatment. STATEMENT OF SIGNIFICANCE: A cationic polymeric
      prodrug with chemotherapeutic self-sensibilization effect was designed and showed
      better inhibition effect on tumor cells proliferation compared with its free
      drug, as well displayed the selective sensibilization effect to tumor cells
      rather than normal cells. Moreover, the prodrug could also deliver MMP-9 shRNA
      plasmid for a combined therapy. As expected, the prodrug possessed excellent gene
      delivery capacity with significant down-regulation expression of MMP-9 protein
      and further inhibition of MCF-7 cells migration. Benefiting from the self
      sensibilization effect and the drug/gene co-delivery strategy, this prodrug
      exhibited significantly improved therapeutic efficacy to breast cancer in a
      combined manner.

PMID- 29369807
TI  - The degradation and transport mechanism of a Mg-Nd-Zn-Zr stent in rabbit common
      carotid artery: A 20-month study.
AB  - : Mg-based stent is a promising candidate of the next generation fully degradable
      vascular stents. The latest progress includes the CE approval of the Magmaris (r)
      WE43 based drug eluting stent. However, so far, the long term (more than 1 year
      implantation) in vivo degradation and the physiological effects caused by the
      degradation products were still unclear. In this study, a 20 month observation
      was carried out after the bare Mg-Nd-Zn-Zr (abbr. JDBM) stent prototype was
      implanted into the common carotid artery of New Zealand white rabbit in order to
      evaluate its safety, efficacy and especially degradation behavior. The
      degradation of the main second phase Mg12Nd was also studied. Results showed that
      the bare JDBM stent had good safety and efficacy with a complete re
      endothelialization within 28 days. The JDBM stent struts were mostly replaced in
      situ by degradation products in 4 month. The important finding was that the
      volume and Ca concentration of the degradation products decreased in the long
      term, eliminating the clinicians' concern of possible vessel calcification. In
      addition, the alloying elements Mg and Zn in the stent could be safely
      metabolized as continuous enrichment in any of the main organs were not detected
      although Nd and Zr showed an abrupt increase in spleen and liver after 1 month
      implantation. Collectively, the long term in vivo results showed the rapid re
      endothelialization of JDBM stent and the long term safety of the degradation
      products, indicating its great potential as the backbone of the fully degradable
      vascular stent. STATEMENT OF SIGNIFICANCE: Mg-based stent is a promising
      candidate of the next generation fully degradable stents, especially after the
      recent market launch of one of its kind (Magmaris). However the fundamental
      question about the long term degradation and metabolic mechanism of Mg-based
      stent and its degradation products remain unanswered. We implanted our patented
      Mg-Nd-Zn-Zr bare stent into the common carotid artery of rabbits and conducted a
      20 months observation. We found that the Ca containing degradation products could
      be further degraded in vivo. All the alloying elements showed no continuous
      enrichment in the main organs of rabbits. These findings eliminate the
      clinicians' concern of possible vessel calcification and element enrichment after
      the implantation of Mg alloy based stents to some extent.

PMID- 29369809
TI  - Pupillographic campimetry: an objective method to measure the visual field.
AB  - Pupillographic campimetry allows measuring the visual field objectively by
      analyzing the pupil response to perimetric stimuli. One of the drawbacks of this
      technique, similar to static perimetry, is the need of reliable fixation of the
      subject. By using stimulus sizes comparable to static perimetry and applying gaze
      tracking, we enable a retinotopic visual field examination regardless of fixation
      problems and with an increased stability and improved spatial resolution. Here,
      we present the results of applying the method in eight normal sighted subjects as
      well as in three patients suffering from diseases usually diagnosed by perimetry.
      The results in normal sighted subjects show a reduction in the amplitude of the
      pupil response with increasing eccentricity as expected. We also demonstrate that
      gaze-controlled campimetry is able to detect organic visual field defects
      objectively in a patient group and classify the visual field defects without an
      organic background. Moreover, we show that our method is able to evaluate the
      visual field sensitivity loss beyond classical perimetry in patients with late
      stage retinitis pigmentosa. Thus, gaze-controlled pupil campimetry can be used in
      addition to classical perimetry, allowing for an objective monitoring of disease
      progression, rendering it as a biomarker for novel treatments.

PMID- 29369810
TI  - Effect of Melissa officinalis capsule on the mental health of female adolescents
      with premenstrual syndrome: a clinical trial study.
AB  - Introduction In spite of its importance, the psychological health requirements of
      adolescents are ignored; due to the occurrence of mental disorders in this age
      group and also public interest in the use of supplementary and alternative
      treatments such as herbal drugs for mental disorders, this study was carried out
      aimed at examining the impact of the Melissa officinalis capsule on the
      psychological health of female adolescents. Methodology In this randomized
      clinical trial study, 100 female adolescents were assigned to two groups of
      either drug and placebo groups. The data collection tool includes demographic
      information recording note and General Health Standard Questionnaire (GHQ).
      Intervention has been done in the menstrual cycle during 3 successive months and
      patients received two 600 mg drug daily in the intervention group, and the
      control group received placebo. After the intervention, the scores of the
      participants' psychological health were measured in both groups and data were
      analyzed through independent t-test using SPSS software version 16. Results The
      study results showed that psychosomatic symptoms score (p < 0.001), anxiety and
      sleeping disorder (p < 0.001), and social function disorder (p = 0.021) in the
      experiment group was significantly less than that of the placebo group.
      Conclusion Based on the findings of this study, Melissa officinalis can decrease
      psychosomatic symptoms, sleeping disorder and anxiety, depression and disorder in
      social function in female adolescents.

PMID- 29369808
TI  - Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a
      key epitope with CENP-A but has a distinct clinical phenotype.
AB  - We studied the clinical correlations and epitopes of autoantibodies directed to a
      novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed
      its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for
      anti-BICD2 using a paramagnetic bead immunoassay and then univariate and
      multivariate logistic regression was used to study the association between anti
      BICD2 and demographic and clinical parameters as well as other SSc-related
      autoantibodies. Epitope mapping was performed on solid phase matrices. 25.7%
      (116/451) SSc sera were anti-BICD2 positive, of which 19.0% had single
      specificity anti-BICD2 and 81.0% had other autoantibodies, notably anti-CENP
      (83/94; 88.3%). Compared to anti-BICD2 negative subjects (335/451), single
      specificity anti-BICD2 subjects were more likely to have an inflammatory myopathy
      (IM; 31.8% vs. 9.6%, p=.004) and interstitial lung disease (ILD; 52.4% vs. 29.0%,
      p=.024). Epitope mapping revealed a serine- and proline-rich nonapeptide
      SPSPGSSLP comprising amino acids 606-614 of BICD2, shared with CENP-A but not
      CENP-B. We observed that autoantibodies to BICD2 represent a new biomarker as
      they were detected in patients without other SSc-specific autoantibodies and were
      the second most common autoantibody identified in this SSc cohort. Our data
      indicate that the major cross-reactive epitope is associated with anti-CENP-A
      but, unlike anti-CENP, single specificity anti-BICD2 antibodies associate with
      ILD and IM.

PMID- 29369811
TI  - Exploration of brushing behavior among university students in Iran: a qualitative
      research.
AB  - Background Currently, it is estimated that 40% of the Iranian population is less
      than 20 years old, and in the academic year of 2011-2012 about 4 million students
      of that age were educated. The general assessment of the outcomes of oral health
      programs and investigating determinants is substantial for developing future
      plans of oral health. This study was done with the aim of exploring brushing
      behavior among university students of Iran to specify and understand the
      important determinants of oral health behavior. Methods A qualitative research
      method was used. This study was conducted between August and November 2016 in
      Shahid Beheshti University. Maximum variation sampling was used among university
      attendees and 44 students with more than 2 years of study duration were selected
      to be included in the research. Semi-structured interviews were employed for data
      gathering. All of the recorded interviews and notes were accurately evaluated and
      data analysis was performed based on the content analysis. Results As a result of
      the interview analysis 16 main categories emerged: Religious Beliefs, Perceived
      Benefits, Perceived Barriers, Habitation, Salience of Behavior, Education,
      Subjective Norms, Peer Pressure, Observational Learning, Knowledge, Perceived
      Susceptibility, Perceived Severity, Outcome Expectation, Skills, Perceived Self
      efficacy, and Perceived Behavioral Control. Codes of sub-theme and theme were
      identified in the study. Conclusion This present study provides additional
      evidence with respect to the religious beliefs and the impact of religious
      instructions in brushing among students. Salience of brushing behavior has been
      described as one of the structures in an integrated behavioral model. Despite
      earlier studies suggesting, that peer pressure only plays a role on children's
      brushing behavior, our study showed that peer pressure is effective on adults as
      well.

PMID- 29369812
TI  - Mainstreaming youth-friendly health services into existing primary health care
      facilities: experiences from South-South Nigeria.
AB  - Background Youth friendly services, an evidence based approach to overcome the
      barriers experienced by youths in accessing care, is poorly implemented. The
      Medical Women's Association of Nigeria (MWAN) Rivers State chapter, was supported
      by Ford Foundation to mainstream youth-friendly health services (YFHS) into
      existing primary health care facilities in two hard-to-reach communities. This
      paper presents the interventions, findings, challenges and recommendations.
      Methods This study project was implemented in stages: design, baseline survey,
      interventions and evaluation, between 2014 and 2016. Interventions included
      facility modifications, health worker capacity building, school and community
      outreaches, peer group activities, and interpersonal communication. Pre-and-post
      intervention surveys were carried out among in- and out-of-school youths to
      determine the effects of the interventions. Results The most commonly stated
      barriers to uptake of youth friendly health services included: unavailability of
      services (154; 33.1%), unavailability of health care workers (167; 38.9%),
      unaffordability of services (108; 45.8%) and difficulty in communicating with
      health workers (85; 36.0%). Post-intervention, utilization improved across all
      services while the perception of barriers to utilization of services reduced (p <
      0.05). The interventions implemented increased the odds of youths utilizing YFHS
      1.81 times (95% CI = 1.39-2.37). Conclusion Facility modifications, capacity
      building of health workers, school and community outreaches, peer group
      activities, and interpersonal communication improved utilization across all
      services while the perception of barriers to utilization of services reduced.
      Implementation of YFHS is impacted by external factors often beyond the control
      of project implementers. Innovative solutions outside of routine health care
      delivery systems are critical for success. Further evaluation to explore the
      effect of these interventions is needed. Strengthening of health systems remains
      a vital strategy for scale-up of YFHS.

PMID- 29369813
TI  - Yoga versus physical exercise for cardio-respiratory fitness in adolescent school
      children: a randomized controlled trial.
AB  - Background Yoga is very effective in improving health especially cardio
      respiratory fitness and also overall performance in adolescents. There are no
      large numbers of randomized controlled studies conducted on comparing yoga with
      physical activity for cardio-respiratory fitness in adolescent school children
      with large sample size. Objective Aerobic training is known to improve physical
      and cardio-respiratory fitness in children. Cardio-respiratory fitness is an
      important indicator of health in children. In this study we evaluate the effects
      of yoga versus physical exercise training on cardio-respiratory fitness in
      adolescent school children. Subjects Eight hundred two school students from 10
      schools across four districts were recruited for this study. Methods In this
      prospective two arm RCT around 802 students were randomized to receive daily one
      hour yoga training (n = 411) or physical exercise (n = 391) over a period of two
      months. VO2 max was estimated using 20 m shuttle run test. However, yoga (n =
      377) and physical exercise (n = 371) students contributed data to the analyses.
      Data was analysed using students t test. Results There was a significant
      improvement in VO2 max using 20 m Shuttle run test in both yoga (p < 0.001) and
      exercise (p < 0.001) group following intervention. There was no significant
      change in VO2 max between yoga and physical exercise group following
      intervention. However, in the subgroup with an above median cut-off of VO2 max;
      there was a significant improvement in yoga group compared to control group
      following intervention (p = 0.03). Conclusion The results suggest yoga can
      improve cardio-respiratory fitness and aerobic capacity as physical exercise
      intervention in adolescent school children.

PMID- 29369814
TI  - Prevalence and determinants of smoking behavior among male school adolescents in
      Saudi Arabia.
AB  - Objective Smoking and tobacco use is a growing public health problem, with often
      begins in adolescence. This study aims to estimate the prevalence of smoking
      behavior and the associated determinants among adolescents. Methods A cross
      sectional study was conducted using a self-administered questionnaire with 453
      male adolescent students in Riyadh, the capital of Saudi Arabia. Descriptive and
      binary logistic regression analyses were performed to aggregate the findings and
      examine associations. Results The prevalence of smoking was 24.3% among
      adolescents. The main predictors of smoking behavior were found to be age (OR =
      1.6; 95% CI: 1.3-2.0; p < 0.001), studying in private schools (OR = 1.4; 95% CI:
      1.2-1.5; p < 0.001), having friends who smoke (OR = 13.9; 95% CI: 6.6-29.9; p <
      0.001), smoking parent (OR = 18.1; 95% CI: 8.8-37.1; p < 0.001), perceived poor
      health (OR = 2.9; 95% CI: 1.9-3.9; p = 0.041) and perceived dissatisfaction with
      life (OR = 4.1; 95% CI: 1.33-13.3; p = 0.017). Smokers were more likely to
      believe that it is difficult to quit smoking (OR = 3.0; 95% CI: 1.6-5.5; p <
      0.001). The top reasons for smoking were having smoker friends (78.2%), family
      neglect (45.5%), having smoker parents (41.8%), family problems (37.3%),
      enjoyment, and having smoker relatives. Conclusion This study concluded that a
      considerable proportion of adolescents are smokers. Adolescents with a smoking
      habit report poorer health and lower life satisfaction than non-smokers. Several
      personal and social factors were identified as important determinants for
      smoking.

PMID- 29369815
TI  - Marijuana use among youths in Mississippi, United States.
AB  - Background Increased use of marijuana among youths in Mississippi, United States
      is of great concern to Public Health in the 21st century. This study examined the
      prevalence of marijuana use according to gender, race and ethnicity. Method The
      data for this study was obtained from Youth Risk Behavior Surveillance System
      (YRBSS) for 2015, a cross-sectional survey of the Mississippi High School
      Students, which examined the prevalence and trends in the use of marijuana
      according to gender, race and ethnicity. The trends in the percentage of students
      that reported the use of marijuana and its product was examined by univariate t
      test statistical analysis at p < 0.05. The frequency distribution was used to
      determine the percentage differences in the groups. Results The students that
      ever used marijuana was 39.4% in Blacks, 39.1% in Hispanics and 31.0% in Whites.
      A total of 13.7% male and female (4.8%) used marijuana before 13 years of age. In
      addition, the students currently using marijuana include Blacks (10.9%), Hispanic
      (13.7%) and Whites (7.2%). Approximately 9.7% of students ever used the synthetic
      product, which was higher in Hispanic (18.7%) when compared to Blacks (8.8%) and
      Whites (9.1%). Conclusion The use of marijuana is significantly higher among the
      male youth in Mississippi than females, which is a major public health concern.
      Furthermore, there was higher rates of smoking marijuana in Hispanics and Blacks
      when compared to White youth.

PMID- 29369816
TI  - Beneficial effect of ghee consumption over mustard oil on lipid profile: A study
      in North Indian adult population.

PMID- 29369817
TI  - Evaluation of management and surgical outcomes in pregnancies complicated by
      acute cholecystitis.
AB  - OBJECTIVE: To evaluate the management of pregnancies complicated by acute
      cholecystitis (AC) and determine whether pregnant women are more likely to have
      medical and surgical complications. METHODS: We carried out a population-based
      matched cohort study using the Healthcare Cost and Utilization Project-Nationwide
      Inpatient Sample from 2003 to 2011. Pregnant women with AC were age matched to
      non-pregnant women with AC on a 1:5 ratio. Management and outcomes were compared
      using descriptive analysis and conditional logistic regression. RESULTS: There
      were 11,835 pregnant women admitted with AC who were age matched to 59,175 non
      pregnant women. As compared to non-pregnant women, women with AC were more
      commonly managed conservatively, odds ratio (OR) 6.1 (5.8-6.4). As compared to
      non-pregnant women, pregnant women with AC more commonly developed sepsis [OR 1.4
      (1.0-1.9)], developed venous thromboembolism [OR 8.7 (4.3-17.8)] and had bowel
      obstruction [OR 1.3 (1.1-1.6)]. Among pregnant women with AC, surgical management
      was associated with a small but significant increased risk of septic shock and
      bile leak. CONCLUSION: AC, in the context of pregnancy, is associated with an
      increased risk of adverse outcomes. Although the literature favors early surgical
      intervention, pregnancies with AC appear to be more commonly managed
      conservatively with overall comparable outcomes to surgically managed AC.
      Conservative management may have a role in select pregnant women with AC.

PMID- 29369818
TI  - Early fetal megacystis: Is it possible to predict the prognosis in the first
      trimester?
AB  - OBJECTIVE: To evaluate the best management of fetal megacystis diagnosed in the
      first trimester and define the prognosis and the most appropriate follow-up as
      early as possible. METHODS: This is a retrospective study of first-trimester
      fetal megacystis diagnosed in pregnant women who performed a combined screening
      for fetal aneuploidy. Megacystis was defined as a longitudinal bladder diameter
      (LBD) greater than 7 mm. All fetuses were divided into two groups according to
      the LBD: Group A with LBD > 15 mm and Group B with LBD < 15 mm. The fetal
      karyotype and associated anomalies were evaluated. Ultrasound monitoring was
      performed every 2 weeks (a second ultrasound scan after 2 weeks from diagnosis
      and a third ultrasound scan 2 weeks after the second one). RESULTS: Twenty-six
      cases were identified between 2011 and 2016; three cases of aneuploidy were
      excluded from the study. Of the remaining 23 cases, 11 were included in Group A
      and 12 in Group B. All Group A fetuses had an adverse outcome. In Group B: five
      (41.7%) cases had an adverse outcome and seven (58.3%) had a spontaneous
      resolution of megacystis. The ultrasound findings of both the ultrasound scans,
      the second and the third, were 100% concordant. CONCLUSION: An ultrasound scan
      performed 2 weeks after the megacystis diagnosis can predict the outcome in
      fetuses with an LBD < 15 mm as early as the end of the first trimester. The
      outcome of euploid fetuses with an LBD < 15 mm was favorable in 58.3% of the
      cases.

PMID- 29369819
TI  - Comparison of flow and gas washout characteristics between pressure control and
      high-frequency percussive ventilation using a test lung.
AB  - OBJECTIVE: A comparison between flow and gas washout data for high-frequency
      percussive ventilation (HFPV) and pressure control ventilation (PCV) under
      similar conditions is currently not available. This bench study aims to compare
      and describe the flow and gas washout behavior of HFPV and PCV in a newly
      designed experimental setup and establish a framework for future clinical and
      animal studies. APPROACH: We studied gas washout behavior using a newly designed
      experimental setup that is motivated by the multi-breath nitrogen washout
      measurements. In this procedure, a test lung was filled with nitrogen gas before
      it was connected to a ventilator. Pressure, volume, and oxygen concentrations
      were recorded under different compliance and resistance conditions. PCV was
      compared with two settings of HFPV, namely, HFPV-High and HFPV-Low, to simulate
      the different variations in its clinical application. In the HFPV-Low mode, the
      peak pressures and drive pressures of HFPV and PCV are matched, whereas in the
      HFPV-High mode, the mean airway pressures (MAP) are matched. MAIN RESULTS: HFPV
      Low mode delivers smaller tidal volume (V T) as compared to PCV under all lung
      conditions, whereas HFPV-High delivers a larger V T. HFPV-High provides rapid
      washout as compared to PCV under all lung conditions. HFPV-Low takes a longer
      time to wash out nitrogen except at a low compliance, where it expedites washout
      at a smaller V T and MAP compared to PCV washout. SIGNIFICANCE: Various flow
      parameters for HFPV and PCV are mathematically defined. A shorter washout time at
      a small V T in low compliant test lungs for HFPV could be regarded as a
      hypothesis for lung protective ventilation for animal or human lungs.

PMID- 29369820
TI  - Assessment of copper nanoparticles (Cu-NPs) and copper (II) oxide (CuO) induced
      hemato- and hepatotoxicity in Cyprinus carpio.
AB  - Recently, Cu-based nanoparticles have drawn considerable attention for their
      various fascinating roles in multiple biological systems. It is recognized that
      their frequent use can create compatibility challenges for the recipient systems.
      Nevertheless, it is unclear how various biological interactions affect the
      compatibility of Cu oxide II (CuO) and Cu oxide nanoparticles (Cu-NPs) for
      different organisms. Consequently, it has been difficult to perform structured
      risk assessments for their use in biological systems. Therefore, this study
      compared the effects of different doses of waterborne Cu-NPs and CuO on the blood
      and liver of selected groups of Cyprinus (C) carpio. These fish while housed in
      suitable water tanks were exposed to one of the following treatments for 14 d:
      control (no added Cu) or 0.5 or 1 or 1.5 mg Cu as Cu-NPs or CuO l-1 of water. We
      found significant changes in all assessed blood parameters of fish in response to
      increasing doses from 0 to 1.5 mg of Cu-NPs or CuO. Similarly, increased levels
      of lipid peroxide and reduced glutathione (GSH) were also observed in the livers
      of C. carpio in Cu-NPs or CuO treated groups. Enhanced levels of lipid
      peroxidation and GSH were also recorded in the Cu-NP treated groups compared with
      the CuO treated groups in a dose dependent manner. The lowest catalase activity
      was observed in the liver of C. carpio treated with the higer dose of Cu-NPs. Cu
      NP or CuO exposure induced significant histological alterations in the liver of
      C. carpio including focal necrosis, cloudy swelling of hepatocytes, degenerative
      hepatocytes, vacuolization, pyknotic nuclei, damaged central vein, nuclear
      hypertrophy, dilated sinusoid, vacuolated degeneration, congestion, and complete
      degeneration in a dose dependent manner. Substantial alterations in blood and
      liver specimens were observed in the Cu-NP treated fish when compared with the
      CuO treated fish. It appeared that the Cu-NPs were more toxic than the CuO as
      shown by the hemato- and hepatotoxicity in C. carpio of this study.

PMID- 29369821
TI  - Non-invasive acquisition of fetal ECG from the maternal xyphoid process: a
      feasibility study in pregnant sheep and a call for open data sets.
AB  - OBJECTIVE: The utility of fetal heart rate (FHR) monitoring can only be achieved
      with an acquisition sampling rate that preserves the underlying physiological
      information on the millisecond time scale (1000 Hz rather than 4 Hz). For such
      acquisition, fetal ECG (fECG) is required, rather than the ultrasound to derive
      FHR. We tested one recently developed algorithm, SAVER, and two widely applied
      algorithms to extract fECG from a single-channel maternal ECG signal recorded
      over the xyphoid process rather than the routine abdominal signal. APPROACH: At
      126dG, ECG was attached to near-term ewe and fetal shoulders, manubrium and
      xyphoid processes (n  =  12). fECG served as the ground-truth to which the fetal
      ECG signal extracted from the simultaneously-acquired maternal ECG was compared.
      All fetuses were in good health during surgery (pH 7.29  +/-  0.03, pO2 33.2  +/-
      8.4, pCO2 56.0  +/-  7.8, O2Sat 78.3  +/-  7.6, lactate 2.8  +/-  0.6, BE  -0.3 
      +/-  2.4). MAIN RESULT: In all animals, single lead fECG extraction algorithm
      could not extract fECG from the maternal ECG signal over the xyphoid process with
      the F1 less than 50%. SIGNIFICANCE: The applied fECG extraction algorithms might
      be unsuitable for the maternal ECG signal over the xyphoid process, or the latter
      does not contain strong enough fECG signal, although the lead is near the
      mother's abdomen. Fetal sheep model is widely used to mimic various fetal
      conditions, yet ECG recordings in a public data set form are not available to
      test the predictive ability of fECG and FHR. We are making this data set openly
      available to other researchers to foster non-invasive fECG acquisition in this
      animal model.

PMID- 29369822
TI  - Remotely controlled fusion of selected vesicles and living cells: a key issue
      review.
AB  - Remote control over fusion of single cells and vesicles has a great potential in
      biological and chemical research allowing both transfer of genetic material
      between cells and transfer of molecular content between vesicles. Membrane fusion
      is a critical process in biology that facilitates molecular transport and mixing
      of cellular cytoplasms with potential formation of hybrid cells. Cells precisely
      regulate internal membrane fusions with the aid of specialized fusion complexes
      that physically provide the energy necessary for mediating fusion. Physical
      factors like membrane curvature, tension and temperature, affect biological
      membrane fusion by lowering the associated energy barrier. This has inspired the
      development of physical approaches to harness the fusion process at a single cell
      level by using remotely controlled electromagnetic fields to trigger membrane
      fusion. Here, we critically review various approaches, based on lasers or
      electric pulses, to control fusion between individual cells or between individual
      lipid vesicles and discuss their potential and limitations for present and future
      applications within biochemistry, biology and soft matter.

PMID- 29369824
TI  - Was the Enalapril Dose Too Low in the PARADIGM-HF Trial?
AB  - Heart failure (HF) is a common clinical syndrome associated with significant
      morbidity and mortality, and there remains a clear need for innovative therapies
      that can modify disease progression. Sacubitril/valsartan (LCZ696) is a novel
      complex that combines simultaneous neprilysin inhibition and angiotensin II
      receptor blockade, that has demonstrated significant cardiovascular death or HF
      hospitalization reduction in the Prospective Comparison of Angiotensin
      Receptor/Neprilysin Inhibitor (ARNI) With Angiotensin-Converting Enzyme (ACE)
      Inhibitors to Determine Impact on Global Mortality and Morbidity in Heart Failure
      (PARADIGM-HF) trial when compared with evidence-based doses of the gold standard
      ACE inhibitor enalapril. In this comprehensive review, the authors discuss
      historical trials that have investigated clinical outcomes utilizing variable
      dosing levels of ACE inhibitors or angiotensin receptor blockers in patients with
      HF with reduced ejection fraction. A critical analysis of the highlighted studies
      is proposed in the context of current HF management guidelines and HF clinical
      practice. In conclusion, based on current evidence, it is unclear whether a
      maximum recommended enalapril dose would promote improved patient outcomes
      compared with an intermediate dose. However, no prospective study to date
      comparing ACE inhibitor doses has documented that higher doses result in
      significant mortality reduction, although the data suggest that there may be a
      decrease in HF hospitalizations when compared with lower doses.

PMID- 29369825
TI  - Patterns of Care and Outcomes of Hypofractionated Chemoradiation Versus
      Conventionally Fractionated Chemoradiation for Glioblastoma in the Elderly
      Population.
AB  - PURPOSE: This study evaluated practice patterns, outcomes, and predictors of
      survival for elderly patients with glioblastoma (GBM) receiving definitive
      chemoradiotherapy (CRT) with either hypofractionated radiotherapy or
      conventionally fractionated radiotherapy. MATERIALS AND METHODS: The National
      Cancer Data Base was queried for patients age 65 years and above diagnosed with
      GBM between 2006 and 2012 that received definitive CRT with either
      hypofractionated radiotherapy (hCRT) or conventionally fractionated radiotherapy
      (cCRT). Patient, tumor, and treatment parameters were extracted. Statistics
      included Kaplan-Meier analysis to evaluate overall survival (OS) as well as Cox
      proportional hazards modeling to determine variables associated with OS.
      Propensity score matching was performed in order to assess groups in a balanced
      manner while reducing indication biases. RESULTS: Altogether, 5126 patients met
      inclusion criteria; 126 (2.5%) underwent hCRT, while 5000 (97.5%) received cCRT.
      Temporal trends revealed that the use of hCRT is rising, especially in more
      recent years. Patients undergoing hCRT were older, with worse performance status,
      treated with biopsy only, and more likely to receive treatment at an academic
      facility. cCRT was associated with improved median OS (10.7 vs. 6.2 mo, P<0.001).
      This persisted in both Cox multivariate analysis (hazard ratio, 0.59; 95%
      confidence interval, 0.49-0.72; P=<0.001) and on propensity-matched analysis
      (median OS 8.7 vs. 6.2 mo; hazard ratio, 0.69; 95% confidence intervcal, 0.53
      0.89; P=0.005). CONCLUSIONS: This is the first study to directly evaluate hCRT
      versus cCRT for patients with GBM. The use of hCRT is rising over time; practice
      patterns of hCRT administration are evaluated. Delivery of hCRT independently
      predicted for poorer OS. Prospective data is recommended to validate the findings
      herein.

PMID- 29369823
TI  - iRhom2 promotes lupus nephritis through TNF-alpha and EGFR signaling.
AB  - Lupus nephritis (LN) often results in progressive renal dysfunction. The inactive
      rhomboid 2 (iRhom2) is a newly identified key regulator of A disintegrin and
      metalloprotease 17 (ADAM17), whose substrates, such as TNF-alpha and heparin
      binding EGF (HB-EGF), have been implicated in the pathogenesis of chronic kidney
      diseases. Here, we demonstrate that deficiency of iRhom2 protects the lupus-prone
      Fcgr2b-/- mice from developing severe kidney damage without altering anti-double
      stranded DNA (anti-dsDNA) Ab production by simultaneously blocking HB-EGF/EGFR
      and TNF-alpha signaling in the kidney tissues. Unbiased transcriptome profiling
      of kidneys and kidney macrophages revealed that TNF-alpha and HB-EGF/EGFR
      signaling pathways are highly upregulated in Fcgr2b-/- mice, alterations that
      were diminished in the absence of iRhom2. Pharmacological blockade of either TNF
      alpha or EGFR signaling protected Fcgr2b-/- mice from severe renal damage.
      Finally, kidneys from LN patients showed increased iRhom2 and HB-EGF expression,
      with interstitial HB-EGF expression significantly associated with chronicity
      indices. Our data suggest that activation of iRhom2/ADAM17-dependent TNF-alpha
      and EGFR signaling plays a crucial role in mediating irreversible kidney damage
      in LN, thereby uncovering a target for selective and simultaneous dual inhibition
      of 2 major pathological pathways in the effector arm of the disease.

PMID- 29369826
TI  - Increase in transmitted drug resistance in migrants from sub-Saharan Africa
      diagnosed with HIV-1 in Sweden.
AB  - OBJECTIVE: To study the trends of transmitted drug resistance (TDR) in HIV-1
      patients newly diagnosed in Sweden, 2010-2016. DESIGN: Register-based study
      including all antiretroviral therapy-naive patients >=18 years diagnosed with HIV
      1 in Sweden 2010-2016. METHODS: Patient data and viral pol sequences were
      extracted from the national InfCareHIV database. TDR was defined as the presence
      of surveillance drug resistance mutations (SDRMs). A CD4 T-cell decline
      trajectory model estimated time of infection. Phylogenetic inference was used for
      cluster analysis. Chi-square tests and logistic regressions were used to
      investigate relations between TDR, epidemiological and viral factors. RESULTS:
      One thousand, seven hundred and thirteen pol sequences were analyzed,
      corresponding to 71% of patients with a new HIV-1 diagnosis (heterosexuals: 53%;
      MSM: 34%). The overall prevalence of TDR was 7.1% (95% CI 5.8-8.3%).
      Nonnucleoside reverse transcriptase inhibitor (NNRTI) TDR increased significantly
      from 1.5% in 2010 to 6.2% in 2016, and was associated to infection and/or origin
      in sub-Saharan Africa (SSA). An MSM transmission cluster dating back to the 1990s
      with the M41L SDRM was identified. Twenty-five (1.5%) patients exhibited TDR to
      tenofovir (TDF; n = 8), emtricitabine/lamivudine (n = 9) or both (n = 8).
      CONCLUSION: NNRTI TDR has increased from 2010 to 2016 in HIV-1-infected migrants
      from SSA diagnosed in Sweden, mirroring the situation in SSA. TDR to
      tenofovir/emtricitabine, used in preexposure prophylaxis, confirms the clinical
      and epidemiological need for resistance testing in newly diagnosed patients.

PMID- 29369828
TI  - Development and External Validation of an Automated Computer-Aided Risk Score for
      Predicting Sepsis in Emergency Medical Admissions Using the Patient's First
      Electronically Recorded Vital Signs and Blood Test Results.
AB  - OBJECTIVES: To develop a logistic regression model to predict the risk of sepsis
      following emergency medical admission using the patient's first, routinely
      collected, electronically recorded vital signs and blood test results and to
      validate this novel computer-aided risk of sepsis model, using data from another
      hospital. DESIGN: Cross-sectional model development and external validation study
      reporting the C-statistic based on a validated optimized algorithm to identify
      sepsis and severe sepsis (including septic shock) from administrative hospital
      databases using International Classification of Diseases, 10th Edition, codes.
      SETTING: Two acute hospitals (York Hospital - development data; Northern
      Lincolnshire and Goole Hospital - external validation data). PATIENTS: Adult
      emergency medical admissions discharged over a 24-month period with vital signs
      and blood test results recorded at admission. INTERVENTIONS: None. MAIN RESULTS:
      The prevalence of sepsis and severe sepsis was lower in York Hospital (18.5% =
      4,861/2,6247; 5.3% = 1,387/2,6247) than Northern Lincolnshire and Goole Hospital
      (25.1% = 7,773/30,996; 9.2% = 2,864/30,996). The mortality for sepsis (York
      Hospital: 14.5% = 704/4,861; Northern Lincolnshire and Goole Hospital: 11.6% =
      899/7,773) was lower than the mortality for severe sepsis (York Hospital: 29.0% =
      402/1,387; Northern Lincolnshire and Goole Hospital: 21.4% = 612/2,864). The C
      statistic for computer-aided risk of sepsis in York Hospital (all sepsis 0.78;
      sepsis: 0.73; severe sepsis: 0.80) was similar in an external hospital setting
      (Northern Lincolnshire and Goole Hospital: all sepsis 0.79; sepsis: 0.70; severe
      sepsis: 0.81). A cutoff value of 0.2 gives reasonable performance. CONCLUSIONS:
      We have developed a novel, externally validated computer-aided risk of sepsis,
      with reasonably good performance for estimating the risk of sepsis for emergency
      medical admissions using the patient's first, electronically recorded, vital
      signs and blood tests results. Since computer-aided risk of sepsis places no
      additional data collection burden on clinicians and is automated, it may now be
      carefully introduced and evaluated in hospitals with sufficient informatics
      infrastructure.

PMID- 29369827
TI  - HIV-positive women have higher risk of human papilloma virus infection,
      precancerous lesions, and cervical cancer.
AB  - OBJECTIVE: HIV-positive women have higher human papillomavirus (HPV) prevalence
      and cervical cancer incidence than HIV-negative women, partly because of HIV's
      modifying effect on HPV pathogenesis. We synthesized the literature on the impact
      of HIV on HPV natural history. DESIGN: Systematic review and meta-analysis.
      METHODS: We searched the literature for studies evaluating HPV acquisition and
      persistence or precancer progression by HIV status. Data on HPV natural history
      by HIV status, CD4 cell counts, viral load, and antiretroviral therapy (ART) were
      summarized using fixed effect models. RESULTS: Overall, 38 of 1845 abstracts
      identified met inclusion criteria. HIV-positive women had higher HPV acquisition
      [relative risk (RRpooled) 2.64, 95% confidence interval (CI) 2.04-3.42] and lower
      HPV clearance (hazard ratiopooled 0.72, 95% CI 0.62-0.84) than HIV-negative
      women. HPV acquisition was higher with declining CD4 cell count and was lower in
      those virally suppressed on ART. HIV was associated with higher incidence of low
      grade squamous intraepithelial lesions (LSIL; RRpooled 3.73, 95% CI 2.62-5.32)
      and high-grade squamous intraepithelial lesions (HSIL; hazard ratiopooled 1.32,
      95% CI 1.10-1.58), largely because of increased HPV persistence. ART lowered
      progression from normal cytology to LSIL (hazard ratiopooled 0.65, 95% CI 0.52
      0.82), but not HSIL. Cervical cancer incidence was associated with HIV positivity
      (RR 4.1, 95% CI 2.3-6.6), but not with ART. CONCLUSION: HIV-positive women have
      higher risk of acquiring HPV, with risk inversely associated with CD4 cell count.
      ART lowered HPV acquisition, increased clearance, and reduced precancer
      progression, likely via immune reconstitution. Although some of our results are
      limited by small number of studies, our study can inform screening guidelines and
      mathematical modeling for cervical cancer prevention.

PMID- 29369829
TI  - Primary Angiitis of the Central Nervous System Mimicking Sporadic Creutzfeldt
      Jakob Disease: A Case Study.

PMID- 29369830
TI  - Population specific genetic heterogeneity of familial hypercholesterolemia in
      South Africa.
AB  - PURPOSE OF REVIEW: To describe the prevalence and population-specific genetic
      heterogeneity of familial hypercholesterolemia in South Africa. RECENT FINDINGS:
      This review highlights the paucity of data on familial hypercholesterolemia in
      South Africa, and the urgent need to uncover the mutation profiles in lipid
      associated genes, causing an increase in LDL-cholesterol in the different ethnic
      groups. Case reports and small studies have shown that familial
      hypercholesterolemia, although apparently uncommon, is present in black Africans.
      SUMMARY: Local founder effects have led to an increased prevalence of familial
      hypercholesterolemia in several South African populations: Afrikaner founder
      mutations (c.681 C>G, c.1285 G>A, c.523 G>A), Ashkenazi founder mutation
      (c.654_656del) and possible Indian founder mutation (c.2054 C>T). Preliminary
      data in black Africans with elevated LDL-cholesterol identified a possible common
      mutation, c.137_142del. The South African multiethnic society and well described
      founder effects emphasize the need for differential approaches to diagnosis and
      management of familial hypercholesterolemia. Studies involving larger cohorts and
      inclusive of different ethnicities are paramount to establishing an accurate
      prevalence of familial hypercholesterolemia in black Africans, not only in South
      Africa but in the Sub-Saharan African region. It is clear that the estimated
      world prevalence of one in 250 cannot be generally applied across African
      populations.

PMID- 29369831
TI  - Novel metabolic phenotypes in lecithin cholesterol acyltyransferase-deficient
      mice.
AB  - PURPOSE OF REVIEW: Lecithin cholesterol acyltyransferase (LCAT) deficiency is a
      rare monogenic disorder causing lipoprotein dysregulation and multiple organ
      dysfunctions, including renal impairment. LCAT knockout mice have been shown
      informative in elucidating mechanisms of many major clinical morbid phenotypes.
      Extended characterization of the LDL receptor/LCAT double knockout (Ldlr/Lcat-DKO
      or DKO) mice had led to the discovery of a number of novel protective metabolic
      phenotypes, including resistance to obesity, nonalcoholic steatohepatitis (NASH)
      and insulin resistance. We seek to integrate the findings to explore novel
      pathogenic pathways. RECENT FINDINGS: The chow fed DKO mice were found more
      insulin sensitive than their Ldlr-KO controls. Joint analyses of the three
      strains (DKO, Ldlr-KO and wild-type) revealed differential metabolic responses to
      a high cholesterol diet (HCD) vs. high-fat diet (HFD). DKO mice are protected
      from HFD-induced obesity, hepatic endoplasmic reticulum (ER) stress, insulin
      resistance, ER cholesterol and NASH markers (steatosis and inflammasomes). Joint
      analysis revealed the HFD-induced NASH is dependent on de-novo hepatic
      cholesterol biosynthesis. DKO mice are protected from HCD-induced hepatic ER
      stress, ER cholesterol, but not NASH, the latter likely due to cholesterol
      crystal accumulation. DKO mice were found to develop ectopic brown adipose tissue
      (BAT) in skeletal muscle. Ectopic BAT derived in part from myoblast in utero and
      from adult satellite cells. Primed expression of PRDM16 and UCP in quiescent
      satellite cell caused by LCAT deficiency synergizes with cell cholesterol
      depletion to induce satellite cell-to-BAT transdifferentiation. SUMMARY:
      Metabolic phenotyping of selective LCAT null mice led to the discovery of novel
      metabolically protective pathways.

PMID- 29369832
TI  - Regression of atherosclerosis: lessons learned from genetically modified mouse
      models.
AB  - PURPOSE OF REVIEW: Regression, or reversal, of atherosclerosis has become an
      important clinical objective. The development of consistent models of murine
      atherosclerosis regression has accelerated this field of research. The purpose of
      this review is to highlight recent mouse studies that reveal molecular mechanisms
      as well as therapeutics targeted for regression. RECENT FINDINGS: Atherosclerosis
      regression does not involve the same mechanisms as progression in reverse order.
      Distinct molecular processes within the plaque characterize regression. These
      processes remained elusive until the advent of murine regression models including
      aortic transplant, the Reversa mouse, gene complementation and dietary
      intervention. Studies revealed that depletion of plaque macrophages is a
      quintessential characteristic of regression, driven by reduced monocyte
      recruitment into plaques, increased egress of macrophages from plaques and
      reduced macrophage proliferation. In addition, regression results in polarization
      of remaining plaque macrophages towards an anti-inflammatory phenotype, smaller
      necrotic cores and promotion of an organized fibrous cap. Furthermore, type 1
      diabetes hinders plaque regression, and several therapeutic interventions show
      promise in slowing plaque progression or inducing regression. SUMMARY: Mouse
      models of atherosclerosis regression have accelerated our understanding of the
      molecular mechanisms governing lesion resolution. These insights will be valuable
      in identifying therapeutic targets aimed at atherosclerosis regression.

PMID- 29369833
TI  - Athletic Remodeling in Female College Athletes, the "Morganroth Hypothesis"
      Revisited.
AB  - BACKGROUND: There is limited data regarding ventricular remodeling in college
      female athletes, especially when appropriate scaling of cardiac dimensions to
      lean body mass (LBM) is considered. Moreover, it is not well established whether
      cardiac remodeling in female athletes is a balanced process with proportional
      increase in left ventricular (LV) mass and volume or the right and LV size.
      METHODS: During the preparticipation competitive screening, 72 female college
      athletes volunteered to undergo dual energy x-ray absorptiometry scan for
      quantification of LBM and comprehensive 2D echocardiography including assessment
      of longitudinal myocardial strain. The athletes were divided in 2 groups
      according to the intensity of the dynamic and static components of their sport
      categories, ie, a higher intensity dynamic and resistive group (n = 37
      participating in rowing, water polo and lacrosse) and a lower intensity group (n
      = 35, participating in short distance running, sailing, synchronized swimming,
      and softball). In addition, we recruited a group of 31 age-matched nonathlete
      controls. RESULTS: The mean age of the study population was 18.7 +/- 1.0 years.
      When scaled to body surface area, the higher intensity group had 17.1 +/- 3.6% (P
      < 0.001) greater LV mass when compared with the lower intensity group and 21.7 +/
      4.0% (P < 0.001) greater LV mass than the control group. The differences
      persisted after scaling to LBM with 14.2 +/- 3.2% (P < 0.001) greater LV mass in
      the higher intensity group. By contrast, there was no difference in any of the
      relative remodeling indices including the LV mass to volume ratio, right to LV
      area ratio, or left atrial to LV volume ratio (P > 0.50 for all). In addition, no
      significant difference was noted among the 3 groups in LV ejection fraction (P =
      0.22), LV global longitudinal strain (P = 0.55), LV systolic strain rate (P =
      0.62), or right ventricular global longitudinal strain (P = 0.61). CONCLUSION:
      Female collegiate athletes participating in higher intensity dynamic and
      resistive sports have higher indexed LV mass even when scaled to LBM. The
      remodeling process does however appear to be a balanced process not only at the
      intraventricular level but also at the interventricular and atrioventricular
      levels.

PMID- 29369834
TI  - Oral Hypertonic Saline Is Effective in Reversing Acute Mild-to-Moderate
      Symptomatic Exercise -Associated Hyponatremia.
AB  - OBJECTIVES: To determine whether oral administration of 3% hypertonic saline
      (HTS) is as efficacious as intravenous (IV) 3% saline in reversing symptoms of
      mild-to-moderate symptomatic exercise-associated hyponatremia (EAH) in athletes
      during and after a long-distance triathlon. DESIGN: Noninferiority, open-label,
      parallel-group, randomized control trial to IV or oral HTS. We used permuted
      block randomization with sealed envelopes, containing the word either "oral" or
      "IV." SETTING: Annual long-distance triathlon (3.8-km swim, 180-km bike, and 42
      km run) at Mont-Tremblant, Quebec, Canada. PARTICIPANTS: Twenty race finishers
      with mild to moderately symptomatic EAH. INDEPENDENT VARIABLES: Age, sex, race
      finish time, and 9 clinical symptoms. MAIN OUTCOME MEASURES: Time from treatment
      to discharge. METHODS: We successfully randomized 20 participants to receive
      either an oral (n = 11) or IV (n = 9) bolus of HTS. We performed venipuncture to
      measure serum sodium (Na) at presentation to the medical clinic and at time of
      symptom resolution after the intervention. RESULTS: The average time from
      treatment to discharge was 75.8 minutes (SD 29.7) for the IV treatment group and
      50.3 minutes (SD 26.8) for the oral treatment group (t test, P = 0.02). Serum Na
      before and after treatment was not significantly different in both groups. There
      was no difference on presentation between groups in age, sex, or race finish
      time, both groups presented with an average of 6 symptoms. CONCLUSIONS: Oral HTS
      is effective in reversing symptoms of mild-to-moderate hyponatremia in EAH.

PMID- 29369835
TI  - Association of aortic valve disease with intestinal angioectasia: data from the
      Nationwide Inpatient Sample.
AB  - OBJECTIVE: Since the description of a correlation between aortic stenosis and
      angioectasia, controversy has persisted about whether these diseases are truly
      associated or coincidental findings of older age. Our objective was to determine
      the association of aortic valve disease and bleeding intestinal angioectasia from
      a large database. PATIENTS AND METHODS: We used the 2011 Nationwide Inpatient
      Sample database to identify hospitalizations in the USA in patients with bleeding
      intestinal angioectasia. International Classification of Diseases, 9th revision,
      Clinical Modification codes were used to identify patients with aortic valve
      disease, mitral valve disease, and known risk factors for angioectasia (including
      diagnosed von Willebrand disease, left ventricular assist device, and chronic
      kidney disease). Univariate and multivariate logistic regression were used to
      determine the odds of association between the valvular diseases and angioectasia.
      RESULTS: A total of 32 079 intestinal angioectasia-related hospitalizations were
      identified of which 7.02% (n=2253) cases had coexistent aortic valve disease. The
      unadjusted odds of aortic valve disease in association with bleeding intestinal
      angioectasia versus those without bleeding angioectasia was 4.95 [95% confidence
      interval: (CI): 4.43-5.54, P<0.001]. The association of intestinal angioectasia
      with mitral valve disease was not significant (odds ratio=1.56, 95% CI: 0.59
      4.14, P=0.38). When adjusted for age and known risk factors, the odds of aortic
      valve disease in bleeding intestinal angioectasia was still significant (odds
      ratio=2.37, 95% CI: 2.10-2.66, P<0.001). CONCLUSION: Our findings support an
      important association between aortic valve disease and bleeding intestinal
      angioectasia, not identified in valvular heart valvular diseases with lower shear
      stress (mitral valve disease).

PMID- 29369836
TI  - Congenital malformation in offspring of female cancer survivors: a national
      cohort study.
AB  - Current evidence on congenital malformations in the offspring of cancer survivors
      is largely inconsistent. Therefore, through this study we aimed to explore the
      prevalence of congenital malformations in the offspring of cancer survivors. To
      this end, female cancer survivors were identified from the Swedish Cancer
      Register and were further linked to the Swedish Medical Birth Register and
      Hospital Discharge Register to identify congenital malformation in their children
      at birth or during adulthood between 1987 and 2010. Multivariate logistic
      regression was used to estimate odds ratios and 95% confidence intervals for the
      association between congenital malformation and maternal cancer diagnosis. A
      total of 816 congenital malformations were noted among 9266 children of maternal
      cancer survivors, and the rate was 8.8%, whereas the rate in the general
      population was 7.7%. After adjusting for some confounding factors, we found that
      the risk for congenital malformation in children of cancer survivors was
      significantly increased with an odds ratio of 1.11 and 95% confidence interval of
      1.04-1.20 as compared with that in controls. The increased risk was largely
      consistent irrespective of maternal age at diagnosis of cancer. The risk for
      congenital malformation was increased among offspring of female cancer survivors,
      which calls for further attention directed toward those cancer survivors who plan
      to have children.

PMID- 29369837
TI  - American Urogynecologic Society Consensus Statement: Cystoscopy at the Time of
      Prolapse Repair.
AB  - Injury to the urinary tract is a known risk of surgical repair of anterior and
      apical pelvic organ prolapse. Cystoscopy at the time of surgical prolapse repair
      is a low-risk procedure that can identify genitourinary tract injury by
      inspecting the bladder and urethra as well as by visualizing the ureters and
      ureteral efflux. There are several techniques to assist with visualization of
      ureteral efflux. Identifying injury intraoperatively may allow for mitigation of
      the morbidity of the injury. Universal cystoscopy should be performed at the time
      of all pelvic reconstructive surgeries, with the exception of operations solely
      for posterior compartment defects.

PMID- 29369838
TI  - Abdominal Sacrocolpopexy for Repair of Pelvic Organ Prolapse After Radical
      Cystectomy.
AB  - INTRODUCTION: Most case series describing surgical repair for pelvic organ
      prolapse (POP) after radical cystectomy (RC) focus on transvaginal repairs. We
      present our experience of POP after RC repaired by abdominal mesh sacrocolpopexy
      (ASC) with long-term follow-up. METHODS: Two women with previous RC with ileal
      conduit diversion underwent open ASC for repair of apical prolapse with
      concomitant enterocele. Prolapse severity was assessed using the POP
      quantification staging system, whereas pelvic imaging was performed with magnetic
      resonance imaging defecography. RESULTS: One patient had no POP recurrence at
      follow-up of 45 months after ASC. The other patient had anterior enterocele
      recurrence at 11 months after ASC and was treated with a limited outpatient
      transvaginal repair. She had no POP recurrence at 12 months after secondary
      repair. Both ASC procedures had technical challenges related to pelvic dissection
      of adhesed loops of bowels, access to the promontory, and retroperitonealization
      requiring the assistance of a general surgeon. Neither case had perioperative
      complications. CONCLUSION: In women with large enterocele or vaginal vault
      prolapse after RC, repair with ASC, although technically challenging, can offer
      durable POP outcomes.

PMID- 29369839
TI  - American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract
      Infection in Adult Women.

PMID- 29369840
TI  - Patients' Knowledge of and Attitude Toward Robotic Surgery for Pelvic Organ
      Prolapse.
AB  - OBJECTIVES: Robotic sacrocolpopexy for pelvic organ prolapse (POP) has increased,
      along with marketing and media coverage. It is unknown whether this exposure
      influences patients' opinions on POP repair. This study describes the preference
      for and knowledge of robotic surgery in women with POP. METHODS: We performed a
      cross-sectional survey of new patients presenting with POP at 7 academic sites.
      Subjects had no prior surgical counseling. A self-administered questionnaire was
      designed to investigate robotic surgery knowledge, preference, and exposure.
      Subjects expressed their preferred route of POP repair (robotic, vaginal,
      abdominal, laparoscopic, or no preference). Knowledge was determined by the
      number of correctly answered questions (range, 0-7). Perception of robotic
      surgery was compared with other surgical routes. RESULTS: One hundred seventy-six
      subjects were included. Most had no surgical preference (66.3%), whereas 27.3%
      preferred nonrobotic and 6.4% preferred robotic routes. The mean knowledge score
      was 2.3 (SD, 1.7). Women preferring robotic surgery were more likely to view it
      as faster than laparoscopic surgery (P < 0.001). These same subjects did not
      perceive any advantages for robotic surgery related to blood loss, pain, and
      organ injury (P > 0.05). Most reported no prior exposure to robotic surgery
      information (56.2%) or advertisements (65.2%). Those with prior exposure most
      frequently obtained information via the Internet and encountered hospital
      advertisements. CONCLUSIONS: The majority of women with POP reported no
      preference for robotic approach to POP surgery. Knowledge about robotic surgery
      was low, even among subjects who expressed preference. Comprehensive counseling
      may help patients make informed decisions even when surgical preferences exist.

PMID- 29369841
TI  - Making Progress in Pelvic Floor Disorders Research: We Can't Do It Alone.

PMID- 29369843
TI  - Smartwatch feedback device for high-quality chest compressions by a single
      rescuer during infant cardiac arrest: a randomized, controlled simulation study.
AB  - OBJECTIVE: According to the guidelines, rescuers should provide chest
      compressions (CC) ~1.5 inches (40 mm) for infants. Feedback devices could help
      rescuers perform CC with adequate rates (CCR) and depths (CCD). However, there is
      no CC feedback device for infant cardiopulmonary resuscitation (CPR). We suggest
      a smartwatch-based CC feedback application for infant CPR. PARTICIPANTS AND
      METHODS: We created a smartwatch-based CC feedback application. This application
      provides feedback on CCD and CCR by colour and text for infant CPR. To evaluate
      the application, 30 participants were divided randomly into two groups on the
      basis of whether CC was performed with or without the assistance of the
      smartwatch application. Both groups performed continuous CC-only CPR for 2 min on
      an infant mannequin placed on a firm table. We collected CC parameters from the
      mannequin, including the proportion of correct depth, CCR, CCD and the proportion
      of correct decompression depth. RESULTS: Demographics between the two groups were
      not significantly different. The median (interquartile range) proportion of
      correct depth was 99 (97-100) with feedback compared with 83 (58-97) without
      feedback (P=0.002). The CCR and proportion of correct decompression depth were
      not significantly different between the two groups (P=0.482 and 0.089). The CCD
      of the feedback group was significantly deeper than that of the control group
      [feedback vs. CONTROL: 41.2 (39.8-41.7) mm vs. 38.6 (36.1-39.6) mm; P=0.004].
      CONCLUSION: Rescuers who receive feedback of CC parameters from a smartwatch
      could perform adequate CC during infant CPR.This is an open-access article
      distributed under the terms of the Creative Commons Attribution-Non Commercial-No
      Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and
      share the work provided it is properly cited. The work cannot be changed in any
      way or used commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 29369845
TI  - Effect of Angiotensin II on Matrix Metalloproteinase-2 Secretion in Human
      Umbilical Vein Endothelial Cells.
AB  - Matrix metalloproteinase (MMP), which is secreted from vascular cells, is an
      enzyme-degrading extracellular matrix protein. MMP molecules, including MMP-2,
      are involved in the destabilization of atherosclerotic plaque and plaque rupture
      during the development of cardiovascular disease. Angiotensin II (Ang-II), a
      vascular stimulant associated with cardiovascular disease progression, has been
      demonstrated to be mainly involved in cardiovascular remodeling of
      atherosclerosis and cardiac hypertrophy. This study was performed to investigate
      the regulation of MMP-2 by Ang-II in human umbilical vein endothelial cells
      (HUVECs). Ang-II significantly increased MMP-2 secretion and MMP-2 messenger RNA
      expression in HUVECs. The effects of Ang-II were suppressed by the coexistence of
      telmisartan, a blocker of the Ang-II receptor type 1 (AT1 receptor), or PD123319,
      a blocker of Ang-II receptor type 2 (AT2 receptor). Especially, PD123319 showed
      marked suppression of the effect of Ang-II on MMP-2. Therefore, Ang-II-induced
      upregulation of MMP-2 in HUVECs was considered to be mainly achieved through AT2
      receptors, although AT1 and AT2 receptors were expressed in HUVECs, but the
      detailed mechanisms remain undefined. These findings suggest that Ang-II can
      enhance MMP-2 mainly through AT2 receptors in endothelial cells, but the
      significance of circulating MMP-2 as a cardiovascular biomarker requires
      confirmation in further clinical studies.

PMID- 29369844
TI  - Modification Patterns of Urinary Albumin Correlates With Serum Albumin and
      Outcome in Severe Alcoholic Hepatitis.
AB  - BACKGROUND AND AIMS: Albumin modifications and deranged functions are well
      documented in serum of severe alcoholic hepatitis (SAH). We investigated whether
      urinary albumin (u-Alb) can serve as surrogate marker of circulatory albumin
      phenotype, functionality, and could predict outcome in SAH patients. PATIENTS AND
      METHODS: Baseline serum and urine samples from 100 SAH, 20 alcoholic cirrhosis,
      and 20 healthy controls were subjected to u-Alb, ischemia modified albumin (IMA),
      IMA to albumin ratio (IMAr), advanced oxidation protein products, advanced
      glycation end-products, albumin-binding capacity determination. In addition, SAH
      urinary samples were also analyzed at day 4 and day 7 to predict nonresponse to
      corticosteroid therapy. RESULTS: Urine and serum levels of IMA, advanced
      oxidation protein products and advanced glycation end-products were higher
      (P<0.05) in SAH versus alcoholic cirrhosis and healthy controls. IMAr was low in
      urine but high in serum of SAH (P<0.05). Albumin-binding capacity was lower
      (P<0.05) in both urinary and serum albumin of SAH. Urinary and serum albumin
      parameters showed direct correlation, whereas IMAr showed inverse correlation
      (cc>0.2, P<0.05). Baseline u-Alb level was significantly higher in SAH, and was
      correlated directly with corticosteroid treatment outcome and 12-month mortality
      in SAH. Baseline u-Alb showed an area under the receivers operating curve
      analysis of 0.7 and a hazard ratio of 1.23 for prediction of 12-month mortality
      in SAH. Baseline u-Alb level >9.0 mg/dL was associated with reduced 12-month
      survival in SAH (log rank <0.01). CONCLUSIONS: u-Alb modifications are reflective
      of serum albumin modifications. Further baseline u-Alb levels could be exploited
      to predict steroid response and mortality in SAH patients.

PMID- 29369846
TI  - Fidget Spinner Ingestion.

PMID- 29369848
TI  - Commentary: Button Batteries in Fidget Spinners: Is It Time to Push the "Panic
      Button"?

PMID- 29369847
TI  - Button Battery Powered Fidget Spinners: A Potentially Deadly New Ingestion Hazard
      for Children.
AB  - Toys entering the marketplace may have unrecognized hazard risks until data on
      injury become known. The fidget spinner is a new popular toy mass marketed to
      children and is primarily sold without warning labels. The US Consumer Product
      Safety Commission has recently issued a formal statement on potential safety
      concerns related to ingestion of the toy parts and other hazards. Button
      batteries within this toy pose the greatest danger to children as ingestion can
      lead to lethal injury. We report 2 cases of children who swallowed a button
      battery from a fidget spinner, causing severe esophageal injury. Various aspects
      of this type of ingestion important for clinicians to be aware of are reviewed.

PMID- 29369849
TI  - Sirtuin 1 regulates pulmonary artery smooth muscle cell proliferation: role in
      pulmonary arterial hypertension.
AB  - OBJECTIVE: Energy metabolism shift from oxidative phosphorylation toward
      glycolysis in pulmonary artery smooth muscle cells (PASMCs) is suggested to be
      involved in their hyperproliferation in pulmonary arterial hypertension (PAH).
      Here, we studied the role of the deacetylase sirtuin1 (SIRT1) in energy
      metabolism regulation in PASMCs via various pathways including activation of
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC
      1alpha), master regulator of mitochondrial biogenesis. APPROACH AND RESULTS:
      Contents of PGC-1alpha and its downstream targets as well as markers of
      mitochondrial mass (voltage-dependent anion channel and citrate synthase) were
      diminished in human PAH PASMCs. These cells and platelet-derived growth factor
      stimulated rat PASMCs demonstrated a shift in cellular acetylated/deacetylated
      state, as evidenced by the increase of the acetylated forms of SIRT1 targets:
      histone H1 and Forkhead box protein O1. Rat and human PASMC proliferation was
      potentiated by SIRT1 pharmacological inhibition or specific downregulation via
      short-interfering RNA. Moreover, after chronic hypoxia exposure, SIRT1 inducible
      knock out mice displayed a more intense vascular remodeling compared with their
      control littermates, which was associated with an increase in right ventricle
      pressure and hypertrophy. SIRT1 activator Stac-3 decreased the acetylation of
      histone H1 and Forkhead box protein O1 and strongly inhibited rat and human PASMC
      proliferation without affecting cell mortality. This effect was associated with
      the activation of mitochondrial biogenesis evidenced by higher expression of
      mitochondrial markers and downstream targets of PGC-1alpha. CONCLUSION: Altered
      acetylation/deacetylation balance as the result of SIRT1 inactivation is involved
      in the pathogenesis of PAH, and this enzyme could be a promising therapeutic
      target for PAH treatment.

PMID- 29369850
TI  - Suture Stenting of a Tube Fenestration for Early Intraocular Pressure Control
      After Baerveldt Glaucoma Implant Surgery.
AB  - PURPOSE: To evaluate the efficacy and safety of a tube fenestration stented with
      a 10-0 polyglactin suture for controlling early postoperative intraocular
      pressure (IOP) after Baerveldt glaucoma implant (BGI) surgery. METHODS: The
      medical records of 110 patients (119 eyes) who underwent BGI surgery with a tube
      fenestration stented with a 10-0 polyglactin suture anterior to an occlusive tube
      ligature were retrospectively reviewed. Main outcome measures included IOP and
      number of glaucoma medications at postoperative day 1, week 1, and weeks 2 to 3
      as well as complications occurring before ligature release. RESULTS: Mean+/-SD
      preoperative IOP was 30.9+/-9.3 mm Hg using an average of 3.8+/-1.1 glaucoma
      medications. A statistically significant reduction in IOP and glaucoma
      medications was observed at all timepoints during the first 3 postoperative weeks
      compared with baseline (P<0.001). Mean IOP on postoperative day 1, week 1, and
      weeks 2 to 3 was 18.4+/-12.2 mm Hg on no medication, 15.9+/-9.4 mm Hg on 1.0+/
      1.3 medications, and 16.7+/-8.2 mm Hg on 1.2+/-1.5 medications, respectively. In
      total, 44 eyes (37%) achieved IOP control without glaucoma medication during
      period of tube occlusion. CONCLUSIONS: The use of a single, monofilament 10-0
      polyglactin suture to stent a fenestration proximal to the occlusive ligature of
      a BGI tube is effective in controlling IOP in the early postoperative period.
      Hypotony-related complications were infrequent and resolved in all cases with in
      office interventions.

PMID- 29369851
TI  - Psychometric Properties of the Glaucoma Treatment Compliance Assessment Tool
      (GTCAT) in a Brazilian Population.
AB  - PURPOSE: To determine the psychometric properties of a reduced version of the
      Glaucoma Treatment Compliance Assessment Tool (GTCAT), which was translated to
      Brazilian Portuguese. PATIENTS AND METHODS: We translated into Portuguese the
      GTCAT using validated techniques and administered it to a group of glaucoma
      patients using at least 1 ocular hypotensive eye drop medication. We used
      principal components analysis to determine construct validity, Rasch analysis,
      and Cronbach alpha for internal consistency reliability, frequency analysis for
      floor and ceiling effects, and Spearman rho for test-retest reliability. RESULTS:
      We included 76 glaucoma patients. Principal component analysis loaded 14
      questions into 7 components that were consistent with the Health Belief Model.
      The components were related to "barriers due to lack of drops," "self-efficacy,"
      "experience of negative effects of the disease," "well-being," "general glaucoma
      knowledge," "glaucoma symptoms," and "cues-to-action." No statements had floor or
      ceiling effects, and all statements had acceptable test-retest reliability.
      Components had internal consistency Cronbach alpha reliability between 0.125 and
      0.794. and average Spearman rho reliability was 0.73, ranging from 0.44 to 1.00.
      According to Rasch analysis, the mean (+/-SD) of the person measures was 0.24+/
      0.15 logits, person separation index was 0.58, and person reliability 0.25.
      CONCLUSIONS: The Portuguese-translated version of the GTCAT showed acceptable
      psychometric properties. With further refinement, clinicians and researchers
      could use it to better investigate glaucoma adherence issues in the Brazilian
      population.

PMID- 29369852
TI  - Nurses at the Bedside-Who Will Be Left to Care?
AB  - Many experienced RNs plan to leave acute care.

PMID- 29369853
TI  - Prioritizing Care Despite Personal Judgments.

PMID- 29369854
TI  - Veterans and Mental Health.

PMID- 29369855
TI  - Nursing Students and Ethical Development.

PMID- 29369856
TI  - Involving Nursing Assistants in Nursing Home QI.
AB  - Staff engagement and input are crucial to project success.

PMID- 29369857
TI  - Nurse-Led Health Clinics Show Positive Outcomes.
AB  - But political and fiscal challenges remain.

PMID- 29369858
TI  - Updated Recommendations for Women's Health.
AB  - ACOG addresses important issues in contraception and cesarean delivery.

PMID- 29369860
TI  - The CDC Updates Guidelines for Congenital Zika.
AB  - New research shows most children with Zika present with only two of the four main
      symptoms.

PMID- 29369862
TI  - Reducing Heart Failure Readmissions Has Risks.
AB  - Study finds mortality rates may increase as readmission rates drop.

PMID- 29369865
TI  - Nurses Pass the Baton: Exit Baby Boomers, Enter Millennials.
AB  - Can this shifting workforce circumvent a nursing shortage?

PMID- 29369866
TI  - Opioid Prescribing in the United States.
AB  - Evidence-based information for nurses on the risks and benefits of prescription
      opioids.

PMID- 29369869
TI  - Removing Practice Barriers.
AB  - States continue to expand practice authority and innovation opportunities for
      APRNS.

PMID- 29369873
TI  - Moving Closer to the 2020 BSN-Prepared Workforce Goal.
AB  - : One of the recommendations of the landmark Future of Nursing: Leading Change,
      Advancing Health report was to increase the proportion of nurses with a bachelor
      of science in nursing or higher degree to 80% by 2020. In 2012, the American
      Organization of Nurse Executives was selected by the Robert Wood Johnson
      Foundation as the National Program Office for a new initiative-the Academic
      Progression in Nursing (APIN) program-with the goal of identifying and developing
      the most promising strategies for creating a more highly educated nursing
      workforce. This article discusses the findings of APIN's four-year project.

PMID- 29369874
TI  - Excessive Dosing of Obeticholic Acid May Increase Risk of Liver Damage.

PMID- 29369875
TI  - FDA Offers Educational Resources on Biosimilar and Interchangeable Products.

PMID- 29369876
TI  - Potential Drug Interactions with Sodium Polystyrene Sulfonate.

PMID- 29369877
TI  - A Multidisciplinary QI Initiative to Improve OR-ICU Handovers.
AB  - : : Background: Handover from the operating room (OR) staff to the ICU staff is a
      critical transition time for patients, in which the potential for error and
      miscommunication is high. Therefore, minimization of extraneous interruptions
      during the exchange of crucial information between the anesthesia and surgical
      teams and the nursing, respiratory therapy, and medical teams is imperative.
      OBJECTIVES: The aim of this quality improvement (QI) initiative was, first, to
      examine the impact of a standardized handover process between the OR and the ICU
      on process and information-sharing errors, and second, to examine provider
      satisfaction with the handover process. METHODS: We conducted prospective
      observations of the handover process before and after implementation of the QI
      initiative. In the pre-process improvement period, 38 cardiothoracic patients
      were observed during handover. In the post-process improvement period, 38
      patients were observed after implementation of the newly developed, standardized
      handover process and communication template. Provider satisfaction surveys were
      distributed at each observation during the pre- and post-process improvement
      periods. RESULTS: Compared with the pre-process improvement period, there was a
      significant decrease in interruptions during report in the post-process
      improvement period (1.7 +/- 1.1 to 0.13 +/- 0.34). There were also significantly
      fewer handover process errors (6.1 +/- 2.8 to 1.7 +/- 1.5), and fewer information
      sharing errors (5.2 +/- 2.7 to 2.3 +/- 1.5). Average report time increased
      slightly, from 13.2 +/- 6.8 minutes to 14.6 +/- 3.8 minutes, but the increase was
      not significant. A total of 211 provider satisfaction surveys were completed in
      the pre-process improvement period and 95 in the post-process improvement period.
      Providers in all disciplines completed surveys in both time periods, and there
      was no significant difference in the percentage of respondents from any
      discipline. Responses to the following survey items showed significant
      improvement in the post-process improvement period: surgery report was
      satisfactory, anesthesia report was satisfactory, could hear all the report, pre
      op anesthesia information was helpful, and start and end of handover were clear.
      Post-process improvement as well, more respondents disagreed that the person
      handing off the patient was under time pressure and that the person taking on
      responsibility for the patient was under time pressure. CONCLUSION: A
      standardized OR-ICU handover process developed by a multidisciplinary team
      decreased handover process and information-sharing errors and increased provider
      satisfaction, with no significant increase in handover time.

PMID- 29369878
TI  - Caring for Aging Skin.
AB  - : This article is part of a series, Supporting Family Caregivers: No Longer Home
      Alone, published in collaboration with the AARP Public Policy Institute. Results
      of focus groups, conducted as part of the AARP Public Policy Institute's No
      Longer Home Alone video project, supported evidence that family caregivers aren't
      given the information they need to manage the complex care regimens of family
      members. This series of articles and accompanying videos aims to help nurses
      provide caregivers with the tools they need to manage their family member's
      health care at home.The articles in this new installment of the series provide
      simple and useful instructions that nurses should reinforce with family
      caregivers who perform wound care tasks. Each article also includes an
      informational tear sheet-Information for Family Caregivers-that contains links to
      instructional videos. To use this series, nurses should read the article first,
      so they understand how best to help family caregivers, and then encourage
      caregivers to watch the videos and ask questions. For additional information, see
      Resources for Nurses.

PMID- 29369879
TI  - The Effect of Yoga on Chronic Nonspecific Low Back Pain.
AB  - Editor's note: This is a summary of a nursing care-related systematic review from
      the Cochrane Library. For more information, see http://nursingcare.cochrane.org.

PMID- 29369880
TI  - The 'IT' Nurse.
AB  - For more than 30 years, Judy Murphy has been a leader in nursing informatics.

PMID- 29369881
TI  - A Brief Meditation on Love, Loss, and Nursing.

PMID- 29369882
TI  - Assessing Aggression Management Programs for Nurses.

PMID- 29369883
TI  - Opioid and Nonopioid Analgesics Provide Similar Relief From Acute Extremity Pain.

PMID- 29369884
TI  - Cataract Surgery is Associated with Lower Mortality in Older Women.

PMID- 29369885
TI  - Percutaneous Coronary Intervention in Stable Angina.

PMID- 29369886
TI  - The Hands.
AB  - A neonatal ICU nurse makes a lasting impression on a new mother.

PMID- 29369887
TI  - Grade Experience of Online Nurse Practitioner Students: Effects of Taking More
      Than 1 Clinical Course per Term.
AB  - This study examined the grade experience for online nurse practitioner students
      (N = 3760) who took more than 1 clinical course per academic term as compared
      with those who did not. Students who had more than 1 clinical course per term had
      a greater percentage of clinical course failures than other students (2.1% vs
      0.8%, P = .001). Nurse practitioner programs should develop clear policies and
      guidelines for students taking more than 1 clinical course at a time.

PMID- 29369888
TI  - Q Methodology: Teaching Strategy to Promote Student Engagement.

PMID- 29369889
TI  - Curriculum Evaluation Using Path Analysis.
AB  - The purpose of this study was to explore the application of path analysis to
      evaluate the curriculum model and provide guidance in course sequencing. Using
      statistical package R to add and subtract various path connections, the
      curriculum model was improved to a proposed curriculum model, which passed the
      exact-fit test (chi42 = 45.612, with P = .286 > .05). Path analysis provided an
      objective method to evaluate the curriculum model and course sequencing in the
      baccalaureate program under study, while informing possible placement of courses.

PMID- 29369890
TI  - Cyclosporine before Coronary Artery Bypass Grafting Does Not Prevent
      Postoperative Decreases in Renal Function: A Randomized Clinical Trial.
AB  - BACKGROUND: Acute kidney injury is a common complication after cardiac surgery,
      leading to increased morbidity and mortality. One suggested cause for acute
      kidney injury is extracorporeal circulation-induced ischemia-reperfusion injury.
      In animal studies, cyclosporine has been shown to reduce ischemia-reperfusion
      injury in the kidneys. We hypothesized that administering cyclosporine before
      extracorporeal circulation could protect the kidneys in patients undergoing
      cardiac surgery. METHODS: The Cyclosporine to Protect Renal Function in Cardiac
      Surgery (CiPRICS) study was an investigator-initiated, double-blind, randomized,
      placebo-controlled, single-center study. The primary objective was to assess if
      cyclosporine could reduce acute kidney injury in patients undergoing coronary
      artery bypass grafting surgery with extracorporeal circulation. In the study, 154
      patients with an estimated glomerular filtration rate of 15 to 90 ml . min . 1.73
      m were enrolled. Study patients were randomized to receive 2.5 mg/kg cyclosporine
      or placebo intravenously before surgery. The primary endpoint was relative plasma
      cystatin C changes from the preoperative day to postoperative day 3. Secondary
      endpoints included biomarkers of kidney, heart, and brain injury. RESULTS: All
      enrolled patients were analyzed. The cyclosporine group (136.4 +/- 35.6%) showed
      a more pronounced increase from baseline plasma cystatin C to day 3 compared to
      placebo (115.9 +/- 30.8%), difference, 20.6% (95% CI, 10.2 to 31.2%, P < 0.001).
      The same pattern was observed for the other renal markers. The cyclosporine group
      had more patients in Risk Injury Failure Loss End-stage (RIFLE) groups R (risk),
      I (injury), or F (failure; 31% vs. 8%, P < 0.001). There were no differences in
      safety parameter distribution between groups. CONCLUSIONS: Administration of
      cyclosporine did not protect coronary artery bypass grafting patients from acute
      kidney injury. Instead, cyclosporine caused a decrease in renal function compared
      to placebo that resolved after 1 month.

PMID- 29369891
TI  - On Coming Back.

PMID- 29369892
TI  - Competence: The Link between Education and Quality Patient Care.

PMID- 29369893
TI  - Effects of Ambient Temperature and Forced-air Warming on Intraoperative Core
      Temperature: A Factorial Randomized Trial.
AB  - BACKGROUND: The effect of ambient temperature, with and without active warming,
      on intraoperative core temperature remains poorly characterized. The authors
      determined the effect of ambient temperature on core temperature changes with and
      without forced-air warming. METHODS: In this unblinded three-by-two factorial
      trial, 292 adults were randomized to ambient temperatures 19 degrees , 21 degrees
      , or 23 degrees C, and to passive insulation or forced-air warming. The primary
      outcome was core temperature change between 1 and 3 h after induction. Linear
      mixed-effects models assessed the effects of ambient temperature, warming method,
      and their interaction. RESULTS: A 1 degrees C increase in ambient temperature
      attenuated the negative slope of core temperature change 1 to 3 h after
      anesthesia induction by 0.03 (98.3% CI, 0.01 to 0.06)  degrees Ccore/(h degrees
      Cambient) (P < 0.001), for patients who received passive insulation, but not for
      those warmed with forced-air (-0.01 [98.3% CI, -0.03 to 0.01]  degrees Ccore/[h
      degrees Cambient]; P = 0.40). Final core temperature at the end of surgery
      increased 0.13 degrees C (98.3% CI, 0.07 to 0.20; P < 0.01) per degree increase
      in ambient temperature with passive insulation, but was unaffected by ambient
      temperature during forced-air warming (0.02 [98.3% CI, -0.04 to 0.09]  degrees
      Ccore/ degrees Cambient; P = 0.40). After an average of 3.4 h of surgery, core
      temperature was 36.3 degrees  +/- 0.5 degrees C in each of the forced-air groups,
      and ranged from 35.6 degrees  to 36.1 degrees C in passively insulated patients.
      CONCLUSIONS: Ambient intraoperative temperature has a negligible effect on core
      temperature when patients are warmed with forced air. The effect is larger when
      patients are passively insulated, but the magnitude remains small. Ambient
      temperature can thus be set to comfortable levels for staff in patients who are
      actively warmed.

PMID- 29369894
TI  - Is the "Appropriate Use Criteria" for Type II Supracondylar Humerus Fractures
      Really Appropriate?
AB  - INTRODUCTION: The Appropriate Use Criteria for the treatment of supracondylar
      humerus fractures (SCHFs), developed by American Academy of Orthopaedic Surgeons,
      recommends pinning for all type II SCHFs. However, previous studies have
      suggested that, with close follow-up some of the less severe type II SCHF's can
      be successfully treated without surgery. Our purpose was to analyze data
      collected prospectively on a large cohort of type II SCHF's. METHODS: We reviewed
      clinical and radiographic information on all type II pediatric SCHF (n=1120) that
      were enrolled in a prospective registry and were followed for a minimum of 8
      weeks. The characteristics of the patients who were treated without surgery were
      compared with those of patients who were ultimately treated surgically. Treatment
      outcomes, as assessed by the final clinical and radiographic alignment, range of
      motion of the elbow, and complications were compared between the groups to define
      clinical and radiographic features that related to success or failure of
      nonoperative management. RESULTS: Ultimately, 812 fractures (72%) were treated
      nonoperatively, and 309 fractures (28%) were treated surgically. At final follow
      up, outcome measures of change in carrying angle, range of motion, and
      complications did not show clinically significant differences between treatment
      groups. Binary logistic regression analysis indicated that initial radiographic
      features, specifically rotational deformity, varus malalignment, valgus
      malalignment, and a shaft-condylar angle of <30 degrees were strongly related to
      selection for surgery. Patients with isolated extension deformity, but none of
      the other features, were more likely to complete successful nonoperative
      management. CONCLUSIONS: Pinning all type II SCHF, as recommended by the
      Appropriate Use Criteria, would have resulted in unnecessary surgery in 72% of
      patients in this series. Given the wide range of injury severity within the type
      II category of SCHF, better discrimination of factors commonly associated with
      successful nonoperative treatment is required. In this particular series,
      fractures with an isolated extension deformity (without rotational or coronal
      malalignment) were more likely to complete successful nonoperative management.

PMID- 29369895
TI  - A Library of Logic Models to Explain How Interventions to Reduce Diagnostic
      Errors Work.
AB  - OBJECTIVES: We aimed to create a library of logic models for interventions to
      reduce diagnostic error. This library can be used by those developing,
      implementing, or evaluating an intervention to improve patient care, to
      understand what needs to happen, and in what order, if the intervention is to be
      effective. METHODS: To create the library, we modified an existing method for
      generating logic models. The following five ordered activities to include in each
      model were defined: preintervention; implementation of the intervention;
      postimplementation, but before the immediate outcome can occur; the immediate
      outcome (usually behavior change); and postimmediate outcome, but before a
      reduction in diagnostic errors can occur. We also included reasons for lack of
      progress through the model. Relevant information was extracted about existing
      evaluations of interventions to reduce diagnostic error, identified by updating a
      previous systematic review. RESULTS: Data were synthesized to create logic models
      for four types of intervention, addressing five causes of diagnostic error in
      seven stages in the diagnostic pathway. In total, 46 interventions from 43
      studies were included and 24 different logic models were generated. CONCLUSIONS:
      We used a novel approach to create a freely available library of logic models.
      The models highlight the importance of attending to what needs to occur before
      and after intervention delivery if the intervention is to be effective. Our work
      provides a useful starting point for intervention developers, helps evaluators
      identify intermediate outcomes, and provides a method to enable others to
      generate libraries for interventions targeting other errors.

PMID- 29369896
TI  - Social Media Crowdsourcing in Health Care Research.

PMID- 29369897
TI  - #colorectalresearch: Introducing a Disruptive Technology for Academic Surgery in
      the Social Media Age.

PMID- 29369898
TI  - Long-term Outcome of Small, Incidentally Detected Rectal Neuroendocrine Tumors
      Removed by Simple Excisional Biopsy Compared With the Advanced Endoscopic
      Resection During Screening Colonoscopy.
AB  - BACKGROUND: Incidental, small rectal neuroendocrine tumors during colonoscopy
      screening are sometimes removed using biopsy forceps. Few studies have examined
      the clinical course of rectal neuroendocrine tumors removed by simple excisional
      biopsy. OBJECTIVE: We investigated the long-term outcome of rectal neuroendocrine
      tumors removed by simple excisional biopsy compared with standard endoscopic
      resection. DESIGN: This was a cohort study. SETTINGS: This study was performed at
      a healthcare center in Korea. PATIENTS: We enrolled patients with rectal
      neuroendocrine tumors detected during a screening colonoscopy between 2003 and
      2015. MAIN OUTCOME MEASURES: The clinical characteristics and long-term outcomes
      (overall survival and disease-free survival) of small neuroendocrine tumors <10
      mm were compared between the simple excisional biopsy group and advanced
      endoscopic resection group. RESULTS: In total, 166 patients were diagnosed with
      rectal neuroendocrine tumors (<=5 mm, n = 100; 6-9 mm, n = 50; 10-19 mm, n = 15;
      >=20 mm, n = 1). Among the 150 patients with neuroendocrine tumors <10 mm, follow
      up endoscopy was performed on 99 (59.6%). All of the tumors were confined to the
      mucosa or submucosa. Thirty-one and 68 patients were included in the simple
      excisional biopsy and advanced endoscopic resection groups. The overall follow-up
      duration was 6.5 years (range, 1.0-12.8 y). Neither overall nor disease-related
      death occurred. Two patients exhibited local recurrence (6.5%, at 8 and 11 y) in
      the simple excisional biopsy group and 1 patient (1.5%, at 7 y) in the advanced
      endoscopic resection group, resulting in no significant difference (p = 0.37).
      All of the recurrences were diagnosed >5 years from initial diagnosis and
      successfully treated endoscopically. LIMITATIONS: More long-term data should be
      warranted. CONCLUSIONS: The long-term outcome of small rectal neuroendocrine
      tumors <10 mm removed by simple excisional biopsy was excellent. Neither overall
      survival nor disease-free survival significantly differed between the simple
      excisional biopsy group and the advanced endoscopic resection group. Thus, simple
      excisional biopsy and long-term follow-up can be cautiously applied for small
      rectal neuroendocrine tumors in clinical practice. See Video Abstract at
      http://links.lww.com/DCR/A406.

PMID- 29369900
TI  - A Pattern-Based Approach Combining Tumor Morphology on MRI With Distinct Signal
      Patterns on Diffusion-Weighted Imaging to Assess Response of Rectal Tumors After
      Chemoradiotherapy.
AB  - BACKGROUND: Diffusion-weighted imaging is increasingly used in rectal cancer MRI
      to assess response after chemoradiotherapy. Certain pitfalls (eg, artefacts) may
      hamper diffusion-MRI assessment, leading to suboptimal diagnostic performance.
      Combining diffusion-weighted MRI with the underlying morphology on standard (T2
      weighted) MRI may help overcome these pitfalls. OBJECTIVE: The purpose of this
      study was to evaluate the diagnostic performance of a pattern-based approach
      combining tumor morphology on T2-weighted MRI with distinct diffusion-weighted
      imaging signal patterns to assess response after chemoradiotherapy in rectal
      cancer. DESIGN: Response to chemoradiotherapy was scored according to 4 patterns:
      1) cases with either a clear residual mass with corresponding high-diffusion
      signal (A+) or completely normalized wall without diffusion signal (A-); 2) cases
      with circular and/or irregular fibrosis with (B+) or without (B-) small foci of
      diffusion signal scattered throughout the fibrosis; 3) cases with semicircular
      fibrosis with (C+) or without (C-) high diffusion signal at the inner margin of
      the fibrosis; and 4) polypoid tumors showing regression of the polyp and fibrosis
      at the site of the stalk with (D+) or without (D-) focal high-diffusion signal in
      the stalk. A total of 75 cases were rescored by an independent second reader to
      study interobserver variations. Standard of reference was histopathology or long
      term outcome. SETTINGS: The study was conducted at a single tertiary referral
      center. PATIENTS: A total of 222 patients with locally advanced rectal cancer
      undergoing chemoradiotherapy were included. MAIN OUTCOME MEASURES: Diagnostic
      performance to discriminate between a complete response and residual tumor was
      measured. RESULTS: The pattern-based approach resulted in a sensitivity of 94%,
      specificity of 77%, positive predictive value of 88%, negative predictive value
      of 87%, and overall accuracy of 88% to differentiate between tumor versus
      complete response. Accuracies per pattern were 100% (A), 74% (B), 86% (C), and
      92% (D). Interobserver agreement was good (kappa = 0.75). LIMITATIONS: The study
      included no comparison with routine (nonpattern) diffusion-MRI assessment.
      CONCLUSIONS: A pattern-based approach combining tumor morphology with distinct
      diffusion-weighted imaging patterns results in good diagnostic performance to
      assess response. See Video Abstract at http://links.lww.com/DCR/A433.

PMID- 29369899
TI  - Incidence and Long-term Implications of Prepouch Ileitis: An Observational Study.
AB  - BACKGROUND: Restorative proctocolectomy is the procedure of choice in patients
      with ulcerative colitis refractory to medical therapy. Prepouch ileitis is
      characterized by mucosal inflammation immediately proximal to the pouch. Prepouch
      ileitis is uncommon, and long-term follow-up data are lacking. OBJECTIVE: The aim
      of this study is to report the long-term outcomes of prepouch ileitis. DESIGN: We
      followed up a cohort of patients with prepouch ileitis that was originally
      described in 2009. Patients were followed up until the last recorded clinic
      attendance or at the point of pouch failure. Follow-up data collected included
      stool frequency, endoscopic findings, treatment, and overall pouch function.
      SETTING: We accessed a prospectively maintained database at our institution
      between January 2009 and January 2017. PATIENTS: Three of the 34 patients
      originally described in 2009 were lost to follow-up; we reanalyzed data on the
      remaining 31. MAIN OUTCOME MEASURE: The rate of pouch failure was defined as the
      need for ileostomy or pouch revision. RESULTS: All 31 patients had coexisting
      pouchitis at index diagnosis of prepouch ileitis. The median length of follow-up
      from the index pouchoscopy was 98 (range, 27-143) months. Seven (23%) patients
      who had an index pouchoscopy with prepouch ileitis went on to pouch failure,
      which is significantly higher than expected (p = 0.03). Five (71%) of these
      patients had chronic pouchitis, and 2 (29%) had small-bowel obstruction due to
      prepouch stricture. Two patients had evidence that would support possible Crohn's
      disease at long-term follow-up. LIMITATIONS: This was a retrospective analysis.
      Because of the nature of the study, there was some missing information that may
      have influenced the results. Our study is further limited by small patient
      numbers. CONCLUSIONS: Prepouch ileitis is associated with a significantly
      increased risk of pouch failure compared with the overall reported literature for
      restorative proctocolectomy. Prepouch ileitis does not appear to be strongly
      predictive of Crohn's disease at long-term follow-up. See Video Abstract at
      http://links.lww.com/DCR/A480.

PMID- 29369901
TI  - The dysfunction of processing task-irrelevant emotional faces in pituitary
      patients: an evidence from expression-related visual mismatch negativity.
AB  - Evidence showed impaired cognitive ability of patients with pituitary adenoma as
      an intracranial tumor. In the present study, we investigated the preattentive
      processing of emotional faces in pituitary adenoma patients by recording and
      analyzing the visual mismatch negativity elicited by deviant emotional faces. In
      the normal control group, deviant emotional faces elicited expression-related
      mismatch negativity (EMMN), with a more pronounced negative waveform for sad than
      happy face conditions. Compared with the normal group, EMMN related to sad faces
      was smaller in patients, whereas the EMMN related to happy faces remained the
      same. These data indicate the functional dysfunction of negative emotional
      processing at the preattentive stage of information processing in pituitary
      adenoma patients.

PMID- 29369903
TI  - Does Prosthesis-Based Breast Reconstruction Affect the Clinical Outcome of
      Postmastectomy Radiotherapy?
AB  - BACKGROUND: In the last 5 decades, there has been significant advancement of
      breast reconstruction and postmastectomy radiotherapy for breast cancer care.
      There has been concern that breast reconstruction may adversely affect the
      efficacy of postmastectomy radiotherapy. This, however, has not been proven by
      clear clinical evidence. METHODS: By comparing the locoregional recurrence rates
      and overall survival after postmastectomy radiotherapy between those with and
      without prosthesis-based breast reconstruction, a retrospective cohort study of
      the breast cancer patients was done. Multivariable Cox proportional hazards
      analysis was used to control the confounding factors. RESULTS: From January 1,
      1998 to December 31, 2011, 1015 patients receiving postmastectomy radiotherapy
      were identified. Among them, 111 patients had prosthesis-based breast
      reconstruction, and the other 904 did not have breast reconstruction. Thirty-four
      of 904 (3.8%) patients in the nonreconstructed group and 4 of 111 (3.6%) patients
      in the reconstructed group developed locoregional recurrence. Multivariable
      survival analysis found no significant difference both in locoregional recurrence
      free survival (hazard ratio, 0.852; P = 0.771) and in overall survival (hazard
      ratio = 1.317; P = 0.246) between the nonreconstructed group and reconstructed
      group. CONCLUSIONS: Although postmastectomy radiotherapy has been shown to affect
      the surgical and cosmetic outcomes of breast reconstruction, prosthesis-based
      breast reconstruction does not seem to have significant adverse impacts on the
      locoregional recurrence-free survival and overall survival of postmastectomy
      radiotherapy.

PMID- 29369902
TI  - Contribution of the alpha5 GABAA receptor to the discriminative stimulus effects
      of propofol in rat.
AB  - Propofol as an agonist of GABAA receptor has a rewarding and discriminative
      stimulus effect. However, which subtype of the GABAA receptor is involved in the
      discriminative stimulus effects of propofol is still not clear. We observed the
      effects of an agonist or an antagonist of the subtype-selective GABAA receptor on
      discriminative stimulus effects of propofol. Male Sprague-Dawley rats were
      trained to discriminate 10 mg/kg (intraperitoneal) propofol from intralipid under
      a fixed-ratio 10 schedule of food reinforcement. We found that propofol produced
      dose-dependent substitution for propofol at 10 mg/kg, with response rate
      reduction only at a dose above those producing the complete substitution.
      CL218,872 (1-3 mg/kg, intraperitoneal), an alpha1 subunit-selective GABAA
      receptor agonist, and SL651,498 (0.3-3 mg/kg, intraperitoneal), an alpha2/3 GABAA
      receptor selective agonist, could partially substitute for the discriminative
      stimulus effects of propofol (40-80% propofol-appropriate responding). Meanwhile,
      L838,417 (0.2-0.6 mg/kg, intravenous), a alpha2/3/5 GABAA receptor selective
      agonist, could produce near 100% propofol-appropriate responding and completely
      substitute for propofol effects. Moreover, the administration of L655,708, the
      alpha5 GABAA receptor inverse agonist, could dose dependently attenuate the
      discriminative stimulus of propofol. In contrast, the alpha1 GABAA receptor
      antagonist beta-CCt (1-3 mg/kg) combined with propofol (10 mg/kg) failed to block
      the propofol effect. The data showed that propofol produces discriminative
      stimulus effects in a dose-dependent manner and acts mainly on the alpha5 GABAA
      to produce the discriminative stimulus effect.

PMID- 29369904
TI  - Efficacy of Lyophilised Platelet-Rich Plasma Powder on Healing Rate in Patients
      With Deep Second Degree Burn Injury: A Prospective Double-Blind Randomized
      Clinical Trial.
AB  - Platelet-rich plasma (PRP) is a kind of plasma that is rich in platelets after
      processing. It includes various growth factors and cytokines, which speed up the
      process of wound healing and hemostasis. The PRP solution used in this study is
      diluted from lyophilized PRP powder, which decreased the possibility of
      contamination, facilitated the storage, and prolonged the storage life. From in
      vitro fibroblast proliferation testing, the numbers of PRP supplement were
      performed for 1, 4, and 7 times by continuous replacement of culture medium each
      day. Four times of lyophilized PRP supplement was selected for clinical study due
      to sufficient promotion of fibroblast proliferation. Next, 27 patients of deep
      second-degree burn wound were included in this study. Patients were assigned to
      two groups: PRP group (n = 15) and control group (n = 12). A concentration of 1.0
      * 10 platelets/cm (wound area) according to wound size was sprayed on the wound
      evenly. Function was mainly assessed by the percentage of wound closure and
      bacteria picking out rate in 2 and 3 weeks. The wound closure at 3 weeks showed a
      significant difference in PRP group (P < 0.05). The healing rate of PRP group
      reached nearly 80% and made a breakthrough of 90% in 3 weeks, showing a
      significant difference compared with the control group (P < 0.05). Lyophilized
      PRP can be considered as an effective treatment to increase healing rate in
      patients with deep second-degree burn injury.

PMID- 29369905
TI  - Floppy Eyelid Syndrome: An Unfamiliar Entity for Plastic Surgeons.
AB  - BACKGROUND: Floppy eyelid syndrome (FES) is typically characterized by chronic
      eye irritation and an increased laxity of the upper eyelid that can be easily
      everted by applying minimal upward traction. However, it is a clinical entity
      that is less known to most plastic surgeons. Blepharoptosis is one of the most
      common features, which links to FES, for which a thorough differential diagnosis
      has become important in directing proper medical treatment. PURPOSE: This review
      aims to discuss current understanding about FES in a broader spectrum,
      encompassing the clinical features and evaluation of FES, the underlying
      etiologies, systemic associations, and surgical procedures for upper eyelid
      tightening. METHODS: The literature search was conducted in Endnote interface
      using the keyword "floppy eyelid" through March 2017. All search abstracts were
      reviewed without language restriction. Citations of identifiable articles were
      also examined. RESULTS: Despite the exact definition of FES remains ambiguous,
      patients with FES often demonstrate unresolvable blepharoptosis, dermatochalasis,
      eyelash ptosis, entropion, or ectropion of the lower eyelid. The pathological
      course of FES can be worrisome because it is often associated with both ocular
      and systemic morbidities, most notably papillary conjunctivitis, keratoconus, and
      obstructive sleep apnea (OSA). Decades of research into the pathogenesis has lent
      further recognition linking the eyelid floppiness with a loss of elastic fibers,
      an increased expression of matrix metalloproteinases, and possible collagen gene
      mutations. Surgery is usually prompted if conservative measures give limited
      responses. High surgical success rates with different follow-up time have been
      reported. CONCLUSIONS: For plastic surgeons, early recognition of FES is
      important because of its chronic, distressing course and the associated
      morbidities. We believe that surgical intervention is the most effective
      treatment of choice. The indication for embarking on surgery is based on the
      clinical severity of the condition. A variety of blepharoplasty techniques for
      FES have been proposed, including full-thickness wedge excision of the tarsus,
      medial and lateral canthal ligament ligation, conchal cartilage graft, lateral
      tarsal strip with flap, and lateral tarsorrhaphy. Most of the procedures have
      provided excellent visual and aesthetic outcomes; therefore, early surgical
      intervention is encouraged if early diagnosis can be made.

PMID- 29369906
TI  - Primary Repair in Patients With Unilateral Complete Cleft of Lip and Primary
      Palate: Assessment of Outcomes.
AB  - OBJECTIVE: Asymmetry of median facial structures is a major concern for patients
      with unilateral cleft lip and palate, and the principal goal of its treatment is
      to restore symmetry. Unilateral complete cleft of lip and primary palate (UCCLPP)
      is an uncommon subgroup and rarely reported. Patients with UCCLPP have protruding
      and deviating premaxilla, rendering a primary repair difficult. This study
      evaluated consecutive patients with UCCLPP and presented their treatment outcome.
      METHODS: We assessed 36 patients with UCCLPP and collected clinical information.
      Surgical repair was performed at 3 months of age by using a modified rotation
      advancement method and primary nasal reconstruction. A single surgeon performed
      all surgical procedures. A postoperative nasal stent was used for 6 months.
      Follow-up standardized photographs were collected. Landmarks were identified, and
      nose and lip dimensions measured. The ratios of the corresponding parameters
      (cleft vs noncleft side) were obtained for evaluating nose and lip symmetry.
      RESULTS: No surgical complication was noted in any patient. The overall lip and
      nose outcome after the primary repair were adequate, and all ratios were close to
      1. The nostril width was slightly wider on the cleft side, but the alar width and
      height were acceptable. The lip heights were balanced between the 2 sides.
      Patients who received presurgical nasoalveolar molding did not show more
      favorable lip and nose dimensions, except for the medial philtral height.
      CONCLUSION: Even in the presence of protruding and deviating premaxilla, our
      patients with UCCLPP obtained adequate lip and nose outcome after undergoing
      primary lip repair and nasal reconstruction.

PMID- 29369907
TI  - Angiogenin Attenuates Scar Formation in Burn Patients by Reducing Fibroblast
      Proliferation and Transforming Growth Factor beta1 Secretion.
AB  - BACKGROUND: Deep burn wounds have a high tendency to form hypertrophic scars.
      Previously, we found that angiogenin promoted neovascularization during deep burn
      wound healing. However, the association between angiogenin and scar formation is
      unclear. METHODS: We obtained human burn scar tissues from patients who underwent
      scar surgery and examined the role of angiogenin in scar tissues and determined
      its effects in scar fibroblasts and on transforming growth factor beta1 (TGF
      beta1) secretion. RESULTS: Our results showed an inverse correlation between
      angiogenin expression and scar severity. Next, we examined the effects of
      angiogenin in scar fibroblasts. We found that angiogenin was persistently
      expressed in human scar fibroblasts and that angiogenin expression significantly
      increased with time in the culture medium of scar fibroblasts. Treatment of scar
      fibroblasts with recombinant angiogenin significantly decreased their
      proliferation and TGF-beta1 secretion. Moreover, angiogenin inhibited TGF-beta1
      mediated Smad2 signaling pathway. CONCLUSION: Our data suggest a negative role of
      angiogenin in fibroblast proliferation via TGF-beta1-mediated Smad2 signaling
      pathway.

PMID- 29369908
TI  - Predominance of CD14+ Cells in Burn Blister Fluids.
AB  - BACKGROUND: Burn blister fluid contains several angiogenic factors to promote
      wound neovascularization. In our previous study, we found that deep partial
      thickness burn (DPTB) wounds showed higher expression levels of angiogenin to
      enhance vascularization compared with superficial partial-thickness burn wounds.
      Neovascularization is a complex process that involves an interaction between
      circulating angiogenic cells and mediators. We hypothesized that in addition to
      angiogenic factors burn blisters may contain specific cell types. The aim of the
      present study was to characterize the specific cells present in burn blisters.
      METHODS: Twenty-four burn blister fluid samples were obtained with informed
      consent from patients with superficial partial-thickness burn (n = 16) or DPTB (n
      = 8) wounds. Blister cells were isolated from individual intact blisters and
      characterized with flow cytometry analysis using CD14, CD34, vascular endothelial
      growth factor receptor 2, and CD133 markers. CD14 and CD34 blister cells were
      also isolated using a magnetic-activated cell sorting system to examine their
      potential for endothelial differentiation. Angiogenin levels in the burn blister
      fluids were evaluated with enzyme-linked immunosorbent assay. RESULTS: CD14 cells
      were the most highly represented cell type in the burn fluids of both groups,
      although a significantly greater percentage of CD14 cells were observed in DPTB
      fluids. CD14 blister cells had a higher potency to differentiate into functional
      endothelial cells as compared with CD34 cells. The proportion of CD14 cells
      gradually increased after burn injury. In contrast to CD14 cells, angiogenin
      showed the highest expression levels at day 1 postburn. With regard to burn wound
      neovascularization, angiogenin expression was partially correlated with CD14
      blister cells in the burn fluids. CONCLUSIONS: We provide the first report on the
      characterization of blister cells in burn fluids. Our data suggest that CD14
      blister cells may play a role in burn wound neovascularization. Measurement of
      CD14 blister cells serves as a possible tool for assessing burn wound status.

PMID- 29369909
TI  - Combined Use of Liposuction and Arthroscopic Shaving for Delayed Debulking of
      Free Flaps in Head and Neck Reconstruction.
AB  - BACKGROUND: Bulky appearance after free flap reconstruction in patients with head
      and neck cancer is common and requires revision to achieve improved final
      outcomes. Although different delayed debulking methods have been reported, the
      procedure can be technically difficult in patients with severe scaring after
      adjuvant radiotherapy. The present study proposes a combined method of
      liposuction and arthroscopic shaving for delayed contouring of free flaps in head
      and neck reconstruction. METHODS: In this study, 12 patients with head and neck
      cancer who had bulky flaps after cancer ablation surgery and immediate free
      anterolateral thigh flap reconstruction were included. These patients underwent
      delayed debulking through the combined arthroscopic shaving and liposuction
      method at least 3 months after the initial reconstruction or the completion of
      adjuvant radiotherapy (if required). Age, sex, cancer stages, the presence or
      absence of adjuvant radiotherapy, the interval between the initial free flap
      reconstruction and the debulking procedure, complications, and subjective
      satisfaction ratings were recorded 1 and 6 months after the revision surgery.
      RESULTS: All patients were men, with an average age of 56.3 years (43-69 years),
      and 9 (75%) patients underwent adjuvant radiotherapy. Partial flap loss was not
      observed in the study patients, and subjective satisfaction ratings improved
      after the debulking procedure. CONCLUSIONS: The combined liposuction and
      arthroscopic shaving method can facilitate the debulking and contouring
      procedures in patients with head and neck cancer after free flap reconstruction.
      With appropriate timing, the combined procedure can be simple and safe, even in
      patients with severe scaring after adjuvant radiotherapy.

PMID- 29369910
TI  - Intensive Care Unit Versus Ward Management After Anterolateral Thigh Flap
      Reconstruction After Oral Cancer Ablation.
AB  - BACKGROUND: Whether postoperative care in the intensive care unit (ICU) is a
      necessity for patients undergoing head and neck free flap reconstruction remains
      debatable. In August 2012, our institute initiated a policy to care for these
      patients in the ICU, opposed to the previous policy of care in the ward. Thus, we
      used this opportunity to compare outcomes between these 2 care approaches.
      PATIENTS AND METHODS: Patients with oral cancer who underwent cancer ablation and
      immediate anterolateral thigh flap reconstruction from August 2010 to July 2014
      were included in this retrospective study. Patients who simultaneously received
      an additional flap reconstruction were excluded. Before August 2012, these
      patients were routinely transferred to the ward for postoperative care (ward
      group, n = 179). Since August 2012, these patients have routinely been
      transferred to the ICU for postoperative care (ICU group, n = 138). RESULTS: Both
      groups had comparable flap outcomes in terms of the rates of take-back,
      successful salvage, flap survival, and flap complication. Compared with the ward
      group, the ICU group showed an increased use of postoperative sedation (26.7% vs
      6.8%, P = 0.000), a correspondingly longer use of mechanical ventilation (3.0 +/-
      2.7 days vs 0.4 +/- 1.4 days, P = 0.000), and a higher incidence of sepsis (3.6%
      vs 0%, P = 0.015). CONCLUSIONS: Postoperative care of patients who have undergone
      anterolateral thigh flap reconstruction after oral cancer ablation in the ward or
      ICU resulted in comparable flap outcomes. Risks and benefits between ward and ICU
      postoperative management in terms of nursing workloads, monitoring facilities,
      use of sedation and mechanical ventilation, and potential for sepsis should be
      taken into consideration when defining postoperative care settings in these
      patients.

PMID- 29369911
TI  - Postoperative Hematoma in Microvascular Reconstruction of the Head and Neck.
AB  - BACKGROUND: Free tissue transfer has become a safe and reliable means for
      repairing soft tissue and bony defects of the head and neck region. Although the
      success rate is high, the incidence of postoperative complications is common. One
      significant complication is postoperative hematoma formation. However, few
      published studies have addressed its incidence, etiology, or outcome. We
      performed a retrospective analysis to investigate this issue. METHODS: A
      retrospective review was conducted of 293 consecutive microvascular free tissue
      transfers in the head and neck region in a single institute from January 2013 to
      December 2015. Patients with postoperative hematoma were identified, and
      demographic data, perioperative conditions, medications, and outcomes were
      evaluated by chart review. RESULTS: A total of 34 patients (11.8%) had
      postoperative hematoma. Compared with the patients without hematoma, this group
      had a longer hospital stay (P = 0.06) and required more secondary procedures (P =
      0.001). The use of nonsteroidal anti-inflammatory drugs (NSAIDs; P < 0.001) was
      associated with a higher incidence of hematoma formation. Among the 34 patients
      with hematoma, 16 (47.1%) had flap compromise and underwent emergent
      reexploration. The salvage rate was higher than that in the nonhematoma group
      (87.5% vs 59.3%, P = 0.086). CONCLUSIONS: Postoperative hematoma after head and
      neck microvascular reconstruction is not a rare complication and may lead to poor
      outcome and more complications. The avoidance of NSAIDs preoperatively may
      prevent hematoma formation. Surgeons should be alert to this situation, and
      immediate return to the operative room for hematoma evacuation is necessary.
      Early intervention may contribute to a high salvage rate.

PMID- 29369912
TI  - Free Flap Transfer for Head and Neck Reconstruction Using Local Anesthesia in
      Elderly Patients.
AB  - BACKGROUND: The incidence of skin cancer appearing on the head and neck areas is
      higher in elderly patients. Although free flap reconstruction is the mainstay
      after tumor excision, it is challenging to complete in elderly patients, owing to
      the high risk of complications and/or mortality rates associated with the use of
      general anesthesia. In this study, we used only local anesthesia in free tissue
      reconstruction of the head and neck in five elderly patients. MATERIALS AND
      METHODS: From 2013 to 2016, 5 elderly patients with high risk of general
      anesthesia underwent reconstruction with either anterolateral thigh free flaps or
      groin free flap under local anesthesia, after wide excision of malignant tumors
      at head and neck. For each patient, the following information was collected: age,
      gender, body weight, anesthesia agents, intravenous fluid, blood loss, site of
      lesion, flap size, operation time, complications, and follow-up time. RESULTS:
      All flaps survived completely. The mean age of 5 patients (3 male patients and 2
      female patients) was 84 years (range, 68-100 years), and mean flap size was 199.6
      cm (range, 120-330 cm). The mean follow-up period was 26.6 months (range, 5-38
      months). No complications were found. CONCLUSIONS: With proper local anesthesia,
      successful head and neck reconstruction with free flap was possible, and patient
      prognosis was positive. There are numerous advantages, including: (1) a safer and
      inexpensive operation; (2) no complications from general anesthesia; (3) the fact
      that free flap transfer can be performed in elderly patients, even if they cannot
      tolerate general anesthesia; and (4) allowance of the performance of free tissue
      transferring in countries without adequate medical resources.

PMID- 29369913
TI  - The Incidence of Necrotizing Fasciitis in Taiwan: A Nationwide Population-Based
      Study.
AB  - BACKGROUND: Little is known about the national population-based incidence rates
      of necrotizing fasciitis (NF) and related epidemiological profiles in Asian
      countries. We plastic surgeons always face and treat this complicated disease in
      the first line at the hospital. METHODS: Using Taiwan's National Health Insurance
      inpatient claims data from 2005 through 2010, we investigated the national annual
      incidence rate of NF by sex, age, year, month, beneficiary category, and region.
      RESULTS: The overall average annual incidence rate (cases per 100,000 population)
      of those 6 years of inpatients with NF was 11.6 (95% confidence interval [CI],
      11.4-11.8) for both sexes, 14.9 (95% CI, 14.9-15.5) for males, and 8.3 (95% CI,
      7.9-8.3) for females. The age-adjusted annual incidence rate was 10.7 (95% CI,
      10.3-11.1) in 2005 and 12.3 (95% CI, 11.9-12.8) in 2010. The annual incidence
      rate increased with age, peaked in August, was the highest in southern Taiwan,
      and correlated with monthly temperature. CONCLUSIONS: The annual incidence rate
      of NF in Taiwan was highest between 2005 and 2009 and slightly lower in 2010 in
      this study. Although additional studies are needed to identify modifiable risk
      factors associated with NF, the aforementioned risk factors alert the first line
      doctors, such as plastic surgeons, to pay much more attention to this complicated
      disease entity and make an accurate critical decision making for the patients.

PMID- 29369914
TI  - A Single-Center, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of
      the Effectiveness of ANT1 Soybean Extract Cream on Skin Recovery After Nd: YAG
      Laser Treatment.
AB  - : Nd:YAG laser has been used extensively for its versatility in treating many
      common aesthetic problems, but numerous adverse effects are often complained by
      recipients of Nd:YAG laser. This study introduces the ANT1 soybean extract cream,
      which was formulated to alleviate adverse effects after laser therapy. This study
      explores whether ANT1 enhances the repair mechanism of the postlaser skin,
      decreases laser-induced complication, and shortens recovery time. The study also
      aims to pinpoint the ANT1 concentration that is most effective in improving the
      skin condition after Nd-YAG laser therapy. MATERIALS AND METHODS: This study was
      a single-center, randomized, double-blind, placebo-controlled trial. Patients
      eligible for the study were Asian women, aged 25 to 40 years, who were free of
      dermatological diseases and allergic reaction. There were a total of 45 subjects.
      Each subject received a session of Nd-YAG laser therapy every 2 weeks, totaling 3
      sessions. Facial skin assessment was achieved via VISIA complexion analysis.
      VISIA complexion analysis quantitatively assessed the skin condition and tracked
      the recovery progress of each subject at baseline, immediately after all 3 laser
      sessions, and a week after the final laser treatment. RESULTS: Skin condition was
      evaluated by VISIA complexion analysis. Skin condition was recorded in aspects of
      pigmented spots, wrinkles, texture, pores, and red area. After Nd-YAG laser
      therapy, postlaser inflammation was observed in all subjects. Throughout the
      laser sessions and the outpatient follow-up clinic, the adverse effects of laser
      therapy, such as redness, spots, wrinkles, pores, and textures, decreased with
      the use of ANT1 cream. There has been a marked effect in wrinkle reduction in the
      patients who received a higher concentration of ANT1 cream (P <= 0.05).
      Statistically significant improvement in spots and pores is also seen (P <=
      0.05). CONCLUSIONS: Through this study, the results suggest that the application
      of ANT1 soybean extract cream ameliorates the complications and enhances the
      cosmetic effects of Nd-YAG laser therapy. A higher concentration of the ANT1
      cream significantly reduces wrinkles and redness after laser. All in all, this
      study proves that the ANT1 soy extract cream may be a useful addition to
      postlaser care for an overall enhancement in skin condition and recovery.

PMID- 29369916
TI  - Diabetes medications and cardiovascular disease: at long last progress.
AB  - PURPOSE OF REVIEW: Although intensive control of hyperglycemia has been proven to
      decrease the risk of microvascular complications in type 2 diabetes, it has had
      little apparent effect on reducing cardiovascular complications - the leading
      cause of mortality in this disease. We review the cardiovascular effects of
      various glucose-lowering medications, with a particular focus on the recent
      studies demonstrating clear benefits from members of several drug categories.
      RECENT FINDINGS: Recently, several randomized controlled studies have revealed
      significant improvements in cardiovascular outcomes from a thiazolidinedione, two
      sodium-glucose cotransporter 2 inhibitors and two glucagon-like peptide 1
      receptor agonists. SUMMARY: These data suggest that certain glucose lowering
      agents after metformin should be favored in type 2 diabetes mellitus patients
      when there is underlying cardiovascular disease.

PMID- 29369915
TI  - Potential role of type I interferon in the pathogenic process leading to type 1
      diabetes.
AB  - PURPOSE OF REVIEW: Understanding the relationship between viral infections and
      the development of type 1 diabetes (T1D) is essential for T1D prevention. Virus
      induced innate immune responses, specifically type I interferon (IFN-I) and the
      IFN gene signature, orchestrate early events of beta-cell dysfunction preceding
      islet autoimmunity. We summarize recent advances in how IFN-I and the IFN gene
      signature can drive T1D development. RECENT FINDINGS: IFN-I, particularly IFN
      alpha, and the IFN gene signature have been detected in islets and peripheral
      blood of T1D patients. T1D risk genes in the IFN-I signaling pathway regulate
      antiviral responses in beta cells driven by IFN-I and proinflammatory cytokines.
      Polymorphisms in these genes may cause chronic dysregulated IFN signaling in
      islets, characterized by hyperexpression of IFN-I, the IFN gene signature, and
      major histocompatibility complex class I during viral infection. Islet-cell
      inflammation mediated by aberrant IFN signaling drives beta-cell apoptosis by
      initiating autoreactivity against beta-cell antigens. The profound elevation in
      IFN-I and the IFN gene signature observed in some forms of T1D are also seen in a
      novel group of human autoimmune and autoinflammatory diseases called
      interferonopathies. SUMMARY: Despite significant advances, further studies are
      required to functionally dissect the mechanisms by which excessive IFN-I
      contributes to the evolution of autoimmunity that destroys beta cells.

PMID- 29369917
TI  - Androgen abuse epidemiology.
AB  - PURPOSE OF REVIEW: To systematically review current epidemiological literature on
      androgen abuse. Estimates from 32 empirical epidemiological articles were
      reviewed. RECENT FINDINGS: Generally, androgen abuse epidemiology and prevalence
      is higher in Europe, the Middle East, North America (the USA), Oceania (Australia
      and New Zealand), and South America (Brazil) and lower in Africa and Asia. In
      contrast to the general population, androgen abuse epidemiology and prevalence is
      higher among athletes, injection drug users, recreational sportspeople, and
      sexual and gender minorities. SUMMARY: From the 1970s, androgen abuse spread from
      athletes into the general population. Consistent with previous evidence, reviewed
      studies suggest that androgen abuse epidemiology and prevalence is higher in
      Western cultural contexts, the Middle East, and South America (Brazil) and lower
      in Africa and Asia. Evidence also corroborates indications that androgen abuse is
      less prevalent among women (vs. men), and in the general population in contrast
      to particular subpopulations consisting of athletes, injection drug users,
      recreational sportspeople, and sexual and gender minorities. Adolescents'
      androgen abuse should be of special concern. Androgen abuse in some nonsports
      occupations (e.g. security workers) requires further exploration. Polypharmacy
      and the Internet proliferation of androgens and other PIEDs require surveillance
      for prevention and harm reduction.

PMID- 29369918
TI  - Public health impact of androgens.
AB  - PURPOSE OF REVIEW: To summarize recent findings regarding the public health
      impact of androgen abuse. RECENT FINDINGS: Abuse of androgens (also called
      'anabolic-androgenic steroids') has grown into a major worldwide substance abuse
      problem involving tens of millions of individuals, of whom about 98% are men.
      Most androgen abusers are still under age 50 today, and thus, the long-term
      effects of these drugs are only beginning to be understood. Recent studies
      confirm that long-term supraphysiologic androgen exposure produces cardiovascular
      toxicity, characterized especially by cardiomyopathy and atherosclerotic disease.
      Withdrawal from androgens after long-term use may produce prolonged and sometimes
      irreversible hypogonadism in men. Supraphysiologic androgen levels may sometimes
      cause irritability, aggressiveness, and violence, whereas androgen withdrawal may
      cause depression. However, these psychiatric effects are idiosyncratic, affecting
      only a minority of users. Emerging evidence now also suggests that long-term
      androgen exposure may cause neurotoxicity, raising the possibility that aging
      androgen abusers may be at increased risk for dementia. Several recent studies
      have also described androgen-induced hepatotoxicity, nephrotoxicity, and adverse
      musculoskeletal effects. SUMMARY: Recent studies have demonstrated marked adverse
      effects of long-term androgen abuse. As increasing numbers of androgen abusers
      reach middle age, these effects will likely represent an emerging public health
      problem.

PMID- 29369919
TI  - Actinomycotic Endometritis.
AB  - Seven cases of actinomycotic endometritis were identified among 28,906
      endometrial biopsies performed in the last 10 yr. The patients' ages ranged from
      44 to 85 yr old. An intrauterine device was in place from 7 to 44 yr. The reasons
      to perform the biopsies included abnormal uterine bleeding, malodor, prolapse,
      pelvic inflammatory disease, and suspicion of metastatic uterine sarcoma.
      Definitive identification of Actinomyces israelii by culture was obtained in 1
      case only. Gram, Gomori methenamine silver, and Fite stains were useful in the
      differential diagnosis with pseudoactinomycotic granules, Nocardia, fungi, and
      other bacteria. The Actinomyces-like organisms were surrounded by extensive
      suppurative reaction in all cases. The tissues showed florid neutrophilic and
      plasmacytic inflammation. The treatment consisted of intrauterine device removal
      and 10 to 30 d of antibiotics in 4 patients. The Actinomyces-like organisms
      persisted for 6 wk in spite of antibiotic therapy when the intrauterine device
      removal was delayed in one of those cases. Two patients had hysterectomy and
      salpingo-oophorectomy due to tubo-ovarian abscess and hysterectomy, salpingo
      oophorectomy, and rectosigmoid excision due to pelvic abscess and septic emboli,
      both followed by 30 to 45 d of antibiotic therapy. One patient had hysterectomy
      not followed by antibiotics due to prolapse. No other pelvic abscesses were
      identified on follow-up, which ranged from 4 to 101 mo (median, 20 mo; mean, 44
      mo).

PMID- 29369920
TI  - Sex Cord-stromal Tumors With Steroid Cell Tumor and Fibroma Components: Report of
      2 Cases, Including One of Extraovarian Origin.
AB  - We report 2 sex cord-stromal tumors with distinct components of fibroma and
      steroid cell tumor; one case was of ovarian and the other of extraovarian origin.
      In the ovarian tumor, there were discrete areas of fibroma and steroid cell
      tumor, not otherwise specified. The extraovarian case involved the pelvic soft
      tissues and comprised a cellular fibroma with subsequent recurrence 7 yr later as
      a steroid cell tumor, not otherwise specified. In both cases, aggregates of
      luteinized cells were present within the fibromatous component, raising the
      possibility that the steroid cell tumor arose from neoplastic transformation of
      these cells. While mixed ovarian sex cord-stromal tumors (gynandroblastomas) are
      well described, as far as we are aware there have been no prior reports of
      neoplasms containing a component of steroid cell tumor and fibroma.

PMID- 29369921
TI  - Microcystic, Elongated, and Fragmented Pattern Invasion in Ovarian Endometrioid
      Carcinoma.

PMID- 29369922
TI  - Canadian Consensus-based and Evidence-based Guidelines for Benign Endometrial
      Pathology Reporting in Biopsy Material.
AB  - Standardized terminology has proven benefits in cancer reporting; in contrast,
      reporting of benign diagnoses in endometrial biopsy currently lacks such
      standardization. Unification and update on the lexicon can provide the structure
      and consistency needed for optimal patient care and quality assurance purposes.
      The Special Interest Group in Gynecologic Pathology of the Canadian Association
      of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) embarked in an
      initiative to address the current need for consensus terminology in benign
      endometrial biopsy pathology reporting. Nine members of the Special Interest
      Group developed a guideline for structured diagnosis of benign endometrial
      pathology through critical appraisal of the available peer-reviewed literature
      and joint discussions. The first version of the document was circulated for
      feedback to a group of professionals in akin fields, the CAP-ACP Executive
      Committee and the CAP-ACP general membership. The final 1-page document included
      17 diagnostic terms comprising the most common benign endometrial entities, as
      well as explanatory notes for pathologists. The proposed terminology was
      implemented in the practice of 5 pathologists from the group, who applied the
      guideline to all benign endometrial biopsies over a 2-wk period. A total of 212
      benign endometrial biopsies were evaluated in this implementation step; the
      recommended terminology adequately covered the diagnosis in 203 cases (95.8%). A
      list of terminology for benign endometrial biopsy reporting, based on expert
      consensus and critical appraisal of the available literature, is presented. On
      the basis of our results of implementation at multiple centers, the proposed
      guideline can successfully cover the large majority of diagnostic scenarios. The
      document has the potential to positively impact patient care, promote quality
      assurance, and facilitate research initiatives aimed at improving histopathologic
      assessment of benign endometrium.

PMID- 29369923
TI  - Primary Ovarian Pregnancy: A Case Series and Analysis.
AB  - The preoperative diagnosis of primary ovarian pregnancy (POP) remains elusive and
      the final diagnosis relies heavily on histologic findings. The diagnostic
      criteria for POP, established in 1878 by Spiegelberg, are based primarily on the
      identification of an embryonic sac within the ovary and the localization of
      conception products therein. However, these diagnostic criteria may be overly
      strict, which may not only significantly underestimate the prevalence of POP, but
      also potentially mislead patient management. In this series, we present 7 cases
      that showed no embryonic sac within the ovary (thus not meeting the Spiegelberg
      criteria for POP), but were nonetheless classified by the authors as POP based on
      the unequivocal presence of chorionic villi and implantation sites within the
      ovary. Immmunohistochemical studies for beta-human chorionic gonadotropin, human
      placental lactogen, and inhibin highlighted the trophoblastic populations. These
      findings indicate that POP may occur even if no embryonic sac is pathologically
      demonstrable. Accordingly, we propose the following modified diagnostic criteria
      for POP: (1) no pathologic evidence of ipsilateral fallopian tube involvement is
      present; and (2) evidences of gestation, including presence of chorionic villi
      and/or implantation site are present within the ovary. If both criteria are met,
      the diagnosis of POP should be rendered. These proposed diagnostic criteria
      should lead to more accurate diagnoses of POP, provide more contemporary insights
      into its true prevalence, heighten clinical awareness of the disease, and
      ultimately, optimize its clinical management.

PMID- 29369925
TI  - Pyogenic granuloma: A tumor that mimics infection.
AB  - This article describes a patient whose cutaneous pyogenic granuloma was mistaken
      for infection after injury from a fractured smartphone screen. Clinicians should
      suspect pyogenic granuloma in patients with these types of injuries so that
      patients can avoid unnecessary procedures, antibiotics, and discomfort.

PMID- 29369926
TI  - Advances in anticoagulation therapy.
AB  - Because atrial fibrillation (AF) is a major risk for thrombotic disease, many
      patients with AF are managed with anticoagulation for primary or secondary
      prevention of these events. The emergence of novel oral anticoagulants offers
      patients and providers options to consider beyond warfarin. Decision making
      should address safety, tolerability, efficacy, price, and simplicity of use; and
      decisions should be individualized for each patient.

PMID- 29369927
TI  - Comparing clinician use of three ankle fracture classifications.
AB  - PURPOSE: This study evaluated the accuracy and interrater reliability of US Army
      physician assistants (PAs) in identifying ankle fracture patterns using existing
      classification schemes. METHODS: Twenty-eight PAs reviewed criteria for
      stability, Danis-Weber, and Lauge-Hansen ankle fracture classification systems.
      Participants reviewed 45 ankle radiographs and independently rated each
      radiograph using these classification schemes. RESULTS: Participants were able to
      successfully identify ankle fracture stability in 82.1% of cases (95% CI, 77.6,
      86.6) with established criteria. Using the Danis-Weber classification, accurate
      classification was achieved in 77.8% of cases (95% CI, 72.8, 82.7). The Lauge
      Hansen classification system was least reliable, with accuracy of 54.5% (95% CI,
      46, 63). CONCLUSION: Referring PAs can reliably discern unstable ankle fractures
      in more than 80% of cases. Lauge-Hansen classification was significantly less
      accurate than the Danis-Weber system or criteria for stability. Good
      communication between orthopedic surgeons and PAs and an emphasis on PA
      orthopedic education can improve patient care.

PMID- 29369928
TI  - An opportunity for PAs as obstetrical laborists.
AB  - The obstetrical laborist, based on the hospitalist model, can improve quality and
      safety of labor and delivery care. A laborist can be a physician assistant (PA),
      certified nurse midwife, or obstetrician/gynecologist who provides care using a
      scheduled shifts model. Workforce trends show a rapid increase in certified nurse
      midwives and PAs, which could stimulate the laborist movement and increase
      opportunities for PAs.

PMID- 29369929
TI  - Carotid dissection mimicking sinusitis.

PMID- 29369930
TI  - Otitis externa.

PMID- 29369933
TI  - What is causing this patient's headache and seizures?

PMID- 29369931
TI  - Identifying acute cervicitis in an era of less-frequent routine gynecologic
      examinations.
AB  - Acute inflammation of the uterine cervix can lead to serious problems such as
      pelvic inflammatory disease (PID), endometritis, and complications of pregnancy
      and childbirth. As intervals for routine gynecologic screening examinations
      lengthen, cervical infections, especially if asymptomatic, may be missed. Annual
      wellness examinations and other patient visits outside routine gynecologic cancer
      screening visits should include brief evaluation with sexual risk assessment and
      a gynecologic examination if indicated. If cervicitis persists after standard
      treatment for sexually transmitted infections (STIs), consider Mycoplasma
      genitalium. Clinicians should be sensitive to the fact that the unexpected
      presence of infection may cause distress.

PMID- 29369934
TI  - Father wounds: Dealing with loss.

PMID- 29369935
TI  - The best that I could be.

PMID- 29369936
TI  - Thoracic outlet syndrome presenting with subclavian vein thrombosis.
AB  - Thoracic outlet syndrome can present with a wide variety of upper extremity
      neurovascular symptoms. Timely clinical recognition is essential for prompt
      treatment and maximal recovery. This article describes a case of thoracic outlet
      syndrome in a volleyball player with an underlying hypercoagulable state who
      presented with a subclavian vein thrombosis.

PMID- 29369938
TI  - Preliminary Work Toward a Transuranic Activity Estimation Method for Rapid
      Discrimination of Anthropogenic from Transuranic Activity in Alpha Air Samples.
AB  - Radon (Rn) and thoron (Rn) progeny (primarily bismuth and polonium) are known
      interferents when rapid evaluation of transuranic content on air filters is of
      interest. These complexities stem from the overlapping energies of the progeny
      alpha particles onto the transuranic region of interest (3-5.5 MeV) where
      naturally-occurring alpha emitters can overwhelm the spectra. Due to the
      immediacy of the alpha counting methods employed, coupled with the half-life of
      thoron progeny dominated by Pb (t1/2=10.6 h), a conservative transuranic activity
      estimate with rigorous uncertainty is being sought. A successful transuranic
      activity estimation method will incorporate any thoron progeny present on the
      filter providing 95% confidence decision levels in which a filter may be
      evaluated for emergency response applications. Twenty-three pairs of samples of
      various duration having no transuranic content were taken over a 2-mo period. The
      resulting filters were counted in a time series before non-linear least squares
      decay curve fitting was applied to the decay profile. For the samples considered,
      a transuranic activity estimator decision level was determined at 0.2 Bq for the
      given geographic location and months analyzed. Validation of this method for
      other seasonal and geographic regions could provide enhanced emergency response
      capability when the presence of transuranic activity is suspected.

PMID- 29369937
TI  - Antifungal Susceptibility and Clinical Outcome in Neonatal Candidiasis.
AB  - BACKGROUND: Invasive candidiasis is an important cause of sepsis in extremely low
      birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in
      neurodevelopmental impairment (NDI) among survivors. We sought to assess the
      antifungal minimum inhibitory concentration (MIC) distribution for Candida in
      ELBW infants and evaluate the association between antifungal resistance and death
      or NDI. METHODS: This was a secondary analysis of a National Institute of Child
      Health and Human Development Neonatal Research Network study. MIC values were
      determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18
      22 months adjusted age using the Bayley Scales of Infant Development. An infant
      was defined as having a resistant Candida isolate if >= 1 positive cultures from
      normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to
      >= 1 antifungal agent. In addition to resistance status, we categorized fungal
      isolates according to MIC values (low and high). The association between
      death/NDI and MIC level was determined using logistic regression, controlling for
      gestational age and Bayley Scales of Infant Development (II or III). RESULTS:
      Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110
      (80%) infants. Three Candida isolates from 3 infants were resistant to
      fluconazole. None were resistant to amphotericin B or micafungin. No significant
      difference in death, NDI, or death/NDI between groups with low and high MICs was
      observed. CONCLUSIONS: Antifungal resistance was rare among infecting Candida
      isolates, and MIC level was not associated with increased risk of death or NDI in
      this cohort of ELBW infants.

PMID- 29369939
TI  - A Pilot Examination of the Methods Used to Counteract Insider Threat Security
      Risks Associated with the Use of Radioactive Materials in the Research and
      Clinical Setting.
AB  - While many organizations maintain multiple layers of security control
      methodologies to prevent outsiders from gaining unauthorized access, persons such
      as employees or contractors who have been granted legitimate access can represent
      an "insider threat" risk. Interestingly, some of the most notable radiological
      events involving the purposeful contamination or exposure of individuals appear
      to have been perpetrated by insiders. In the academic and medical settings,
      radiation safety professionals focus their security efforts on (1) ensuring
      controls are in place to prevent unauthorized access or removal of sources, and
      (2) increasing security controls for the unescorted accessing of large sources of
      radioactivity (known as "quantities of concern"). But these controls may not
      completely address the threat insiders represent when radioactive materials below
      these quantities are present. The goal of this research project was to
      characterize the methodologies currently employed to counteract the insider
      security threat for the misuse or purposeful divergence of radioactive materials
      used in the academic and medical settings. A web-based survey was used to assess
      how practicing radiation safety professionals in academic and medical settings
      anticipate, evaluate, and control insider threat security risks within their
      institutions. While all respondents indicated that radioactive sources are being
      used in amounts below quantities of concern, only 6 % consider insider threat
      security issues as part of the protocol review for the use of general radioactive
      materials. The results of this survey identify several opportunities for
      improvement for institutions to address security gaps.

PMID- 29369940
TI  - A Case Study of the NCRP 156 Wound Model of Embedded DU Using Data From Urine
      Uranium Concentrations of Wounded Veterans.
AB  - Depleted uranium (DU) munitions were initially used by the United States (U.S.)
      military during the first Persian Gulf War in 1991 in order to penetrate heavily
      armored vehicles. However, as a result of friendly fire, several U.S. military
      personnel received intakes from DU munitions. One of the ongoing concerns for
      these wounded veterans is the potential long-term exposure received from DU
      embedded fragments. The United States Army Institute of Public Health (AIPH) is
      the first laboratory that analyzes the urine bioassays from Army Soldiers that
      are injured with DU fragments. The United States Air Force School of Aerospace
      Medicine also evaluates bioassays from DU injuries. The urine bioassay data
      collected by AIPH was evaluated using the NCRP 156 wound model coefficients for
      the DU-Wafer, Fragment, and Particle models. The maximum likelihood method was
      used in the Integrated Modules for Bioassay Analysis (IMBA-PPAE) to calculate the
      estimates of intake and tissue doses. Evaluating the three models for wound
      retention, the DU-Wafer and Fragment model yielded a credible fit to the bioassay
      data. Comparing the two models, the DU-Wafer model fits the data better than the
      Fragment model when comparing their autocorrelation coefficient and chi-squared
      values of (P 1.73 * 10, c 4.83 * 10), (P 2.01 * 10, c 1.09), respectively. This
      evaluation supports the validity of both the DU-wafer model as well as the
      default fragmentation model proposed by NCRP 156.

PMID- 29369941
TI  - Comment on: 'beta Blocker use and mortality in cancer patients: systematic review
      and meta-analysis of observational studies' (Zhong et al., 2015; published Epub
      ahead of print 3 September 2015).

PMID- 29369942
TI  - Computed Tomography Images of the Scapula Taken With Reduced Dose Can Yield
      Segmented Models of Sufficient Accuracy: A Pilot Study.
AB  - OBJECTIVE: The aim of the study was to investigate the influence of tube current
      reduction on the segmentation accuracy of the scapula. METHODS: A human cadaver
      was computed tomography scanned multiple times while reducing tube current
      amperage. The images were segmented using 2 different segmentation methods (N =
      28). Subsequently the scapula was dissected and all soft tissues were removed. An
      optical laser scan of the dissected scapula was aligned and compared with the
      segmented meshes of the different computed tomography scans. RESULTS: The mesh
      accuracy remained fairly constant with diminishing tube currents. All segmented
      meshes had a larger volume than the reference mesh (n = 27). The mean 3
      dimensional deviation varied between 1.17 mm (max) and -0.759 mm (min) and the
      total mean (SD) 3-dimensional deviation was -0.45 (0.38) mm. Radiation dosages
      were reduced from 7.1 to 0.3 mSv. CONCLUSIONS: Computed tomography tube current
      can be largely reduced without losing the surface segmentation accuracy of
      segmented scapula meshes.

PMID- 29369943
TI  - Dependence of Scan Parameters on Nerve Fiber Crossing Depiction in Diffusion
      Spectrum Imaging in Clinical Practice.
AB  - OBJECTIVE: The objective of this study was to show the effect of the number of
      sampling points (NS) and the maximum b value (bmax) on fiber crossing detection
      in diffusion spectrum imaging (DSI) in clinical practice. METHODS: We performed 3
      Tesla DSI in which we changed the NS (62-258) while keeping bmax at 8000 s/mm and
      in which we changed the bmax (4000-8000 s/mm) while keeping the NS at 129. The
      superior longitudinal fasciculus volume and the proportion of nerve voxels in
      which at least 2 (Rcr2) or 3 (Rcr3) nerve fiber bundles crossed were calculated.
      RESULTS: When bmax was set to 8000 s/mm, mean Rcr2 and Rcr3 values and superior
      longitudinal fasciculus volumes significantly increased with higher NSs, but they
      did not significantly change when we varied bmax with 129 NS. CONCLUSIONS:
      Depiction sensitivity of nerve fiber crossing in DSI improves at higher NS and
      bmax settings, but a bmax insensitivity appears at an intermediate NS such as
      129.

PMID- 29369944
TI  - Virtual Monoenergetic Images From a Novel Dual-Layer Spectral Detector Computed
      Tomography Scanner in Portal Venous Phase: Adjusted Window Settings Depending on
      Assessment Focus Are Essential for Image Interpretation.
AB  - OBJECTIVE: We aimed to determine optimal window settings for conventional
      polyenergetic (PolyE) and virtual monoenergetic images (MonoE) derived from
      abdominal portal venous phase computed tomography (CT) examinations on a novel
      dual-layer spectral-detector CT (SDCT). METHODS: From 50 patients, SDCT data sets
      MonoE at 40 kiloelectron volt as well as PolyE were reconstructed and best
      individual window width and level values manually were assessed separately for
      evaluation of abdominal arteries as well as for liver lesions. Via regression
      analysis, optimized individual values were mathematically calculated. Subjective
      image quality parameters, vessel, and liver lesion diameters were measured to
      determine influences of different W/L settings. RESULTS: Attenuation and contrast
      to-noise values were significantly higher in MonoE compared with PolyE. Compared
      with standard settings, almost all adjusted W/L settings varied significantly and
      yielded higher subjective scoring. No differences were found between manually
      adjusted and mathematically calculated W/L settings. CONCLUSIONS: PolyE and MonoE
      from abdominal portal venous phase SDCT examinations require appropriate W/L
      settings depending on reconstruction technique and assessment focus.

PMID- 29369945
TI  - Conventional and Diffusional Magnetic Resonance Imaging Features of Mitochondrial
      Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes in Chinese Patients:
      A Study of 40 Cases.
AB  - PURPOSES: The aims of the study were to analyze the conventional and diffusion
      weighted MRI (DWI) of mitochondrial encephalomyopathy, lactic acidosis, and
      stroke-like episodes (MELAS) and to investigate underlying mechanisms. METHODS:
      Features of 58 acute and 68 chronic stroke-like lesions as well as global brain
      abnormalities of 40 Chinese MELAS patients were analyzed. RESULTS: Gyriform DWI
      hyperintensity with decreased apparent diffusion coefficient (ADC) and patchy DWI
      hyperintensity with normal ADC were noted in 56 of 58 and 2 of 58 cortical
      regions of acute lesions, respectively. High ADC and mix of low and high ADC were
      observed in 51 of 58 and 5 of 58 affected subcortical white matters,
      respectively. Lacunar infarcts existed in 23 of 40 patients. Among 17 patients
      who have been followed, recurrence, progression, and progressive atrophy were
      noted in 8, 9, and 4 cases, respectively. CONCLUSIONS: This study demonstrates
      the conventional and diffusional MRI features of MELAS, suggesting a model of
      acute stroke-like lesions in which the cortex manifest with cytotoxic edema and
      the subcortical area with vasogenic edema.

PMID- 29369946
TI  - Gynecological Lymphoma: A Case Series and Review of the Literature.
AB  - OBJECTIVE: The aim of the study was to evaluate the radiological characteristics
      of gynecological lymphoproliferative disease (LPD) and specific imaging features
      that may suggest the diagnosis. METHODS: Two readers conducted a retrospective
      evaluation of imaging studies of 13 female patients presenting with a
      gynecological LPD. A literature review was also performed. RESULTS: Of the 13
      evaluated women, 9 had ovarian involvement, 3 had cervical involvement, and 1 had
      uterine involvement. The most common lesion characteristics were homogenous
      masses (11), with mild contrast enhancement (9), followed by soft-tissue necrosis
      (4), prominent blood vessels displaced by the lesions (4), linear arrangement of
      cysts at the periphery of the ovaries (3), and "touching" ovaries in all cases of
      bilateral ovarian involvement. CONCLUSIONS: A solid large homogeneous mass with
      mild contrast enhancement should alert the radiologist to the possibility of the
      differential diagnosis of LPD. Radiologists should be "the gatekeepers" by
      raising this possibility to avoid unnecessary surgery and enable appropriate
      treatment.

PMID- 29369947
TI  - Hepatocellular Carcinoma: Retrospective Evaluation of the Correlation Between
      Gadobenate Dimeglumine-Enhanced Magnetic Resonance Imaging and Pathologic Grade.
AB  - OBJECTIVE: The aim of this study was to evaluate the usefulness of gadobenate
      dimeglumine-enhanced magnetic resonance imaging in characterizing the grade of
      hepatocellular carcinoma (HCC) using the signal intensity (SI) of the erector
      spinae as internal reference. MATERIALS AND METHODS: Clinical data of 40 patients
      (a total of 44 lesions) confirmed by pathology for HCC were retrospectively
      reviewed. Gadobenate dimeglumine-enhanced magnetic resonance imaging was
      performed in all patients, and SI of lesions (SIles), liver parenchyma around the
      lesions (SIhep), erector spinae (SImus) and standard deviation of SI of the
      surrounding noise (SDnoi) on nonenhanced T2WI, nonenhanced T1WI, and contrast
      enhanced T1WI (in both arterial and hepatobiliary phase [AP and HBP]) were
      measured, respectively. Contrast-to-noise ratio (CNR) were separately defined as
      CNR1 ([SIles - SIhep]/SDnoi) and CNR2 ([SIles - SImus]/SDnoi). Statistical
      analyses were performed using one-way analysis of variance, least significant
      difference test, logistic regression analysis, Spearman rank correlation, and
      receiver operating characteristic curves analysis. RESULTS: Forty-four HCCs,
      including 3 well-differentiated HCCs, 26 moderately differentiated HCCs, and 15
      poorly differentiated (PD) HCCs, were confirmed. On logistic regression analysis,
      only CNR2 in the HBP was predictor of PD HCCs (P = 0.015, odds ratio = 1.040).
      The size of lesions, CNR1 in the AP, CNR2 in the AP, and CNR2 in the HBP, showed
      significant correlations with the degree of differentiation (correlation
      coefficients = -0.371, 0.435, 0.503, and 0.512, respectively; P = 0.013, 0.003,
      0.001, and 0.000, respectively). Contrast-to-noise ratio 2 in the HBP with the
      cutoff of less than 4.56 could distinguish moderately differentiated HCCs from PD
      HCC with the sensitivity and specificity of 84.6% and 60.0%, respectively.
      CONCLUSIONS: Relatively low arterial enhancement and low CNR2 value in the HBP
      are predictive for poor histological grade of HCCs.

PMID- 29369949
TI  - Using Choice Architecture to Integrate Substance Use Services with Primary Care:
      Commentary on Donohue et al.
AB  - : At a time when death and disability linked to problematic substance use have
      reached crisis levels, integration of substance use disorder (SUD) services into
      primary care settings is a clear national priority. Incentive-based interventions
      can catalyze such adoption, but have thus far demonstrated limited
      efficaciousness. Behavioral Economics can inform efforts to incentivize
      healthcare providers to adopt SUD interventions. Choice architecture principles
      dictate pegging rewards to defined quality metrics, improving provider
      information about effective and cost-effective practices, and reducing barriers
      to SUD service provision through technological tools, tackling stigma, and
      addressing real and perceived regulatory burdens and risks. Additional research
      is needed to inform these and other key elements in the choice environment
      designed to facilitate the integration of SUD care into primary care. Success in
      the deployment of the "cascade of care" model in primary care settings during the
      HIV/AIDS epidemic provides room for optimism, but also underscores the urgency of
      rapid scale-up in diagnostic and treatment services for SUD to address the
      burgeoning opioid crisis.

PMID- 29369948
TI  - Prognostic Value of Volume-Based Metabolic Parameters Obtained by 18F-FDG-PET/CT
      in Patients With Locally Advanced Squamous Cell Cervical Carcinoma.
AB  - OBJECTIVE: The aim of the study was to assess the prognostic impact of volume
      based metabolic F-fluorodeoxyglucose-positron emission tomography/ computed
      tomography (F-FDG-PET/CT) parameters in patients with stage IB-IVA squamous cell
      cervical carcinoma (SCCC). MATERIALS AND METHODS: We reviewed the pretreatment F
      FDG-PET/CT records of 67 patients with stage IB-IVA SCCC. The maximum
      standardized uptake value (SUVmax) of the primary tumor (PSUVmax), highest SUVmax
      of the whole malignant lesions (WSUVmax), metabolic tumor volume (MTV) of the
      primary tumor (PMTV), MTV of the whole malignant lesion (WMTV), total lesion
      glycolysis (TLG) of primary tumor (PTLG), and TLG of the whole malignant lesion
      (WTLG) were obtained. Univariate and multivariate analyses were performed to
      assess the predictive values of metabolic parameters. RESULTS: Twenty-nine
      patients showed disease progression and 21 patients died during follow-up. In
      univariate analysis, positive lymph node, WSUVmax of greater than 11, WMTV of
      greater than 63 cm, and WTLG of greater than 373 adversely affected the
      progression-free survival (P = 0.004, 0.045, 0.023, and 0.005, respectively). A
      positive lymph node, WSUVmax of greater than 12, WMTV of greater than 68 cm, and
      WTLG of greater than 373 significantly adversely affected overall survival (P =
      0.002, 0.032, 0.015, and 0.006, respectively). In multivariate analysis,
      independent prognostic factor for progression-free survival was WTLG (relative
      risk = 2.384, 95% confidence interval = 1.095-5.187, P = 0.029). Independent
      prognostic factors for overall survival was WTLG (relative risk = 2.763; 95%
      confidence interval = 1.107-6.896, P = 0.029). CONCLUSIONS: Preliminary results
      indicated that pretreatment WTLG measured by F-FDG-PET/CT could independently
      predict survival in patients with locally advanced SCCC.

PMID- 29369950
TI  - Importance of Speed and Power in Elite Youth Soccer Depends on Maturation Status.
AB  - Murtagh, CF, Brownlee, TE, O'Boyle, A, Morgans, R, Drust, B, and Erskine, RM.
      Importance of speed and power in elite youth soccer depends on maturation status.
      J Strength Cond Res 32(2): 297-303, 2018-Maturation status is a confounding
      factor when identifying talent in elite youth soccer players (ESP). By comparing
      performance of ESP and control participants (CON) matched for maturation status,
      the aims of our study were to establish the importance of acceleration, sprint,
      horizontal-forward jump, and vertical jump capabilities for determining elite
      soccer playing status at different stages of maturation. Elite youth soccer
      players (n = 213; age, 14.0 +/- 3.5 years) and CON (n = 113; age, 15.0 +/- 4.4
      years) were grouped using years from/to predicted peak height velocity (PHV) to
      determine maturation status (ESP: pre-PHV, n = 100; mid-PHV, n = 25; post-PHV, n
      = 88; CON: pre-PHV, n = 44; mid-PHV, n = 15; post-PHV, n = 54). Participants
      performed 3 reps of 10- and 20-m sprint, bilateral vertical countermovement jump
      (BV CMJ), and bilateral horizontal-forward CMJ (BH CMJ). Elite youth soccer
      players demonstrated faster 10-m (p < 0.001) and 20-m sprint (p < 0.001)
      performance than CON at all stages of maturation. Mid-PHV and post-PHV ESP
      achieved greater BV CMJ height (p < 0.001) and BH CMJ distance (ESP vs. CON; mid
      PHV: 164.32 +/- 12.75 vs. 136.53 +/- 21.96 cm; post-PHV: 197.57 +/- 17.05 vs.
      168.06 +/- 18.50 cm; p < 0.001) compared with CON, but there was no difference in
      BV or BH CMJ between pre-PHV ESP and CON. Although 10 and 20 m and sprint
      performance may be determinants of elite soccer playing status at all stages of
      maturation, horizontal-forward and vertical jumping capabilities only
      discriminate ESP from CON participants at mid- and post-PHV. Our data therefore
      suggest that soccer talent identification protocols should include sprint, but
      not jump assessments in pre-PHV players.

PMID- 29369951
TI  - Performance Differences Among Skilled Soccer Players of Different Playing
      Positions During Vertical Jumping and Landing.
AB  - Harry, JR, Barker, LA, James, CR, and Dufek, JS. Performance differences among
      skilled soccer players of different playing positions during vertical jumping and
      landing. J Strength Cond Res 32(2): 304-312, 2018-Both jumping and landing
      performance of skilled soccer players is diminished when task demands are
      increased. However, it is unclear if performance changes are specific to players
      of certain playing positions. Therefore, we assessed jumping and landing
      performance among skilled soccer players of different playing positions. Twenty
      five National Collegiate Athletic Association (NCAA) Division 1 male soccer
      players (179.5 +/- 7.8 cm, 75.5 +/- 7.1 kg, 19.7 +/- 1.2 years) performed maximum
      effort vertical jump landings (VJLs), whereas vertical ground reaction force
      (vGRF) data were obtained. Participants were stratified into goalkeeping (GK),
      defensive (DEF), midfield (MID), and attacking (ATT) group according to their
      primary playing position. One-way analyses of variance (alpha = 0.05) and effect
      sizes (ESs; large >= 0.80) were used to compare differences among groups. The
      jumping phase variables evaluated were jump height, unloading and amortization
      vGRF magnitudes, eccentric rate of force development, and the reactive strength
      index. Landing phase variables included the peak vGRF magnitude, vGRF loading
      rate, vGRF attenuation rate, and landing time. No statistically significant
      differences were detected for any jumping or landing variable (p >= 0.05).
      However, a number of large magnitude differences were detected during landing
      after ES calculations. Specifically, greater peak vGRF magnitudes were detected
      in DEF vs. both MID (ES = 1.08) and ATT (ES = 0.93), a greater vGRF loading rate
      occurred in DEF vs. MID (ES = 0.93), and a greater vGRF attenuation rate occurred
      in DEF vs. both MID (ES = 1.00) and AT (ES = 0.80). It is concluded that highly
      skilled soccer players possess position-specific abilities with respect to the
      landing phase of VJL. Skilled soccer players might experience enhanced training
      outcomes after VJL training regimens tailored to the specific demands of their
      primary playing position.

PMID- 29369952
TI  - Running Performance in Brazilian Professional Football Players During a Congested
      Match Schedule.
AB  - Palucci Vieira, LH, Aquino, R, Lago-Penas, C, Munhoz Martins, GH, Puggina, EF,
      and Barbieri, FA. Running performance in Brazilian professional football players
      during a congested match schedule. J Strength Cond Res 32(2): 313-325, 2018-The
      purpose of the study was to examine the influence of playing congested fixtures
      (2 matches a week) on running performance of Brazilian professional football
      players, pooled (all performance files regardless players' rotation between
      games) or individualized data treatment (including only files of athletes' who
      played pair(s) of noncongested-congested matches which occurred on the same
      week). Forty participants were observed 1-37 times during 59 official matches
      over 3 years. Global positioning system devices were used to compute total
      distance covered, maximal sprinting speed mean speed (VAVERAGE), and high
      intensity activities (HIA: >=15 km.h). Independent variables included match
      status (win, draw, and lose), location (home and away), opponent quality (weak
      and strong), competitive standard (national and state), team formation (4-4-2 and
      4-3-3), and position (defender, midfielder, and forward). Student's t-test,
      effect sizes (d), and magnitude-based inferences were performed to detect
      differences between congested and noncongested fixtures for each independent
      factor. Overall, pooled and individualized data treatment revealed contrasting
      results. The first showed chances of positive outcomes playing congested matches
      (possibly to very likely; d = 0.09-0.55), for all variables, as using 4-4-2 and
      state tournament. Conversely, individualized data analysis revealed that during
      national leagues (possibly; d = 0.24) or forward position (likely; d = 0.70), the
      players presented reduced HIA when played congested than noncongested periods (p
      <= 0.05). Using 4-3-3 (d = 0.26) or when draw (d = 0.41), possibly lower HIA was
      also identified. Coaching staff should be aware of performance oscillations such
      as detrimental effects on HIA during congested periods.

PMID- 29369953
TI  - Preseason Maximal Aerobic Power in Professional Soccer Players Among Different
      Divisions.
AB  - Marcos, MA, Koulla, PM, and Anthos, ZI. Preseason maximal aerobic power in
      professional soccer players among different divisions. J Strength Cond Res 32(2):
      356-363, 2018-The purpose of this study was to examine and compare the
      anthropometric, maximal oxygen uptake (V[Combining Dot Above]O2max), and
      positional differences of first division (D1) professional football players from
      players of second (D2) and third (D3) divisions in Cyprus football leagues. Four
      hundred twenty-one professional male football players participated in this study.
      All subjects underwent anthropometric and body composition evaluation. In
      addition, they performed an incremental cardiopulmonary exercise testing (CPET)
      on a treadmill for V[Combining Dot Above]O2max evaluation. The results were
      analyzed using 1-way analysis of variance, between subjects design revealing
      significant effects among the divisions. Tukey's honest significant difference
      (HSD) tests demonstrated that players from D1 scored significantly higher on
      V[Combining Dot Above]O2max and lasted significantly longer on the treadmill than
      participants of D2 and D3 (p <= 0.05). Similar findings were demonstrated when D2
      was contrasted against D3 players. Goalkeepers, defenders, and forwards
      demonstrated significantly higher anthropometric measurements, whereas wingers
      and midfielders demonstrated significantly higher V[Combining Dot Above]O2max (p
      <= 0.05) than goalkeepers and defenders. The findings of this study clearly
      demonstrated that cardiovascular fitness, as determined by CPET, is an important
      fitness parameter that differentiates professional football players who play at a
      more advanced level. This could be attributed to the different seasonal schedules
      that allow for longer transition time for lower division players and thus
      favoring greater detraining effects. Emphasis should be given by fitness
      professionals on transition period training to minimize the detraining effects
      especially in lower divisions.

PMID- 29369954
TI  - Short-Term Training Cessation as a Method of Tapering to Improve Maximal
      Strength.
AB  - Pritchard, HJ, Barnes, MJ, Stewart, RJC, Keogh, JWL, and McGuigan, MR. Short-term
      training cessation as a method of tapering to improve maximal strength. J
      Strength Cond Res 32(2): 458-465, 2018-The aim of this study was to determine the
      effects of 2 different durations of training cessation on upper- and lower-body
      maximal strength performance and to investigate the mechanisms underlying
      performance changes following short-term training cessation. Eight resistance
      trained males (23.8 +/- 5.4 years, 79.6 +/- 10.2 kg, 1.80 +/- 0.06 m, relative
      deadlift 1 repetition maximum of 1.90 +/- 0.30 times bodyweight [BW]) each
      completed two 4-week strength training periods followed by either 3.5 days (3.68
      +/- 0.12 days) or 5.5 days (5.71 +/- 0.13 days) of training cessation. Testing
      occurred pretraining (T1), on the final day of training (T2), and after each
      respective period of training cessation (T3). Participants were tested for
      salivary testosterone and cortisol, plasma creatine kinase, psychological
      profiles, and performance tests (countermovement jump [CMJ], isometric midthigh
      pull, and isometric bench press [IBP]) on a force plate. Participants' BW
      increased significantly over time (p = 0.022). The CMJ height and IBP peak force
      showed significant increases over time (p = 0.013, 0.048, and 0.004,
      respectively). Post hoc testing showed a significant increase between T1 and T3
      for both CMJ height and IBP peak force (p = 0.022 and 0.008 with effect sizes of
      0.30 and 0.21, respectively). No other significant differences were seen for any
      other measures. These results suggest that a short period of strength training
      cessation can have positive effects on maximal strength expression, perhaps
      because of decreases in neuromuscular fatigue.

PMID- 29369955
TI  - Reliability of Near-Infrared Spectroscopy for Measuring Intermittent Handgrip
      Contractions in Sport Climbers.
AB  - Balas, J, Kodejska, J, Krupkova, D, Hannsmann, J, and Fryer, S. Reliability of
      near-infrared spectroscopy for measuring intermittent handgrip contractions in
      sport climbers. J Strength Cond Res 32(2): 494-501, 2018-The use of near-infrared
      spectroscopy (NIRS) to investigate muscle oxygenation changes during physical
      tasks such as rock climbing has rapidly increased within recent years; yet, there
      is no known measure of reliability. The current study aimed to determine
      intersession reliability and minimal detectable change (MDC) of continuous wave
      NIRS parameters during intermittent handgrip contractions in rock climbers.
      Thirty-two sport climbers were tested for exhaustive intermittent handgrip
      exercise (8-second contraction-2-second relief) at 60% of maximal voluntary
      contraction on 3 separate days. During each visit, continuous wave NIRS was used
      to determine tissue saturation index (TSI) as the measure of tissue oxygenation
      in the flexor digitorum profundus. To assess the intersession reliability, the
      intraclass correlation coefficient (ICC), SEM, coefficient of variation (CV), and
      MDC were used. Mean deoxygenation during the contractions provided reliable
      results ([INCREMENT] TSI; first trial -8.9 +/- 2.9%, second trial -8.8 +/- 2.7%,
      and third trial -8.4 +/- 2.6%; ICC = 0.692; SEM = 1.5%; CV = 17.2%; MDC = 4.2%).
      Mean muscle reoxygenation during the relief periods was similarly reliable
      ([INCREMENT] TSI; first trial 9.0 +/- 3.1%, second trial 8.8 +/- 2.9%, and third
      trial 8.5 +/- 2.7%; ICC = 0.672; SEM = 1.7%; CV = 19.0%, MDC = 4.7%). As such,
      continuous wave NIRS provides a reliable measure of deoxygenation and
      reoxygenation during intermittent contractions to failure in the forearm flexors
      of rock climbers. Differences exceeding ~4.5% for [INCREMENT] TSI during
      contraction and relief periods should be considered meaningful.

PMID- 29369956
TI  - Comparison of Exercise Performance in Recreationally Active and Masters Athlete
      Women.
AB  - Stone, MS, Glenn, JM, Vincenzo, JL, and Gray, M. Comparison of exercise
      performance in recreationally active and masters athlete women. J Strength Cond
      Res 32(2): 565-571, 2018-Master athletes (MA) are an understudied, ever-growing
      cohort. As such, it is important to examine how age affects muscular power and
      fatigability. Of particular interest is muscular power maintenance and fatigue
      mitigation of MA compared with young, healthy adults. The purpose of this
      investigation was to examine the differences in peak power, average power, total
      work (WRK), and fatigue index (FI) between recreationally active (RA) younger
      adults and female MA during anaerobic cycling exercise. Two groups, RA (n = 15;
      20.6 +/- 0.8 years) and MA (n = 17; 50.5 +/- 8.6 years), participated in this
      study. Peak power, APWR, WRK, and FI were measured during a 30-second Wingate
      maximum anaerobic cycling protocol at a predetermined resistance of 7.5% body
      mass. Peak power (p = 0.92; RA: 654.1 +/- 114.5 W; MA: 658.6 +/- 147.6 W), APWR
      (p = 0.09; RA: 429.8 +/- 73.3 W; MA: 384 +/- 73.8 W), WRK (p = 0.09; RA: 12,894.3
      +/- 2,198.3 J; MA: 18,044.3 +/- 27,184.9 J), and FI (p = 0.30; RA: 11.8 +/- 4.1
      W.s; MA: 14 +/- 5.2 W.s) were not significantly different between groups. Master
      athletes produce power and WRK comparable to rates of fatigue among RA. This
      suggests that MA can maintain physical ability similar to RA in multiple
      parameters of high-intensity exercise while mitigating fatigue comparably. These
      data allow for advancements in exercise training and performance outcomes in MA
      populations. Further research within the MA population is warranted regarding
      other aspects of exercise and sport performance.

PMID- 29369957
TI  - Plasma Ropivacaine Concentrations Following Local Infiltration Analgesia in Total
      Knee Arthroplasty: A Pharmacokinetic Study to Determine Safety Following Fixed
      Dose Administration.
AB  - BACKGROUND AND OBJECTIVES: The primary aim of this study was to examine the
      pharmacokinetics of ropivacaine in patients undergoing elective total knee
      arthroplasty with local infiltration analgesia as the primary analgesic method.
      We also sought to determine the incidence of biochemical toxicity through
      measurement of plasma ropivacaine concentrations over the first 24 hours
      postoperatively. METHODS: This was a prospective, observational study of 15
      patients undergoing elective total knee arthroplasty. Local infiltration
      analgesia was administered by standard technique with 300 mg ropivacaine and
      epinephrine 5 MUg/mL. Total ropivacaine concentrations were taken at specified
      time intervals in the 24 hours after tourniquet release and analyzed by liquid
      chromatography-mass spectrometry. RESULTS: Fifteen patients were enrolled into
      the study. The median peak ropivacaine concentration was 0.57 MUg/mL, with a
      range of 0.32 to 0.88 MUg/mL, and occurred between 6 and 24 hours. Age (P =
      0.04), weight (P = 0.04), creatinine (P = 0.02), and female sex (P = 0.03) were
      important predictors of peak concentration. Age (P = 0.02), female sex (P =
      0.01), and baseline alpha1 acid glycoprotein concentrations (P = 0.03) were
      important predictors for the area under the curve from a ropivacaine
      concentration versus time plot. CONCLUSIONS: The peak total ropivacaine
      concentration was below quoted toxic concentrations (2.2 MUg/mL) in all patients.
      This peak occurred later than has previously been described in those undergoing
      neuraxial or peripheral nerve block, occurring between 6 and 24 hours. The
      influence of age, weight, and renal function on systemic ropivacaine
      concentration should be considered when planning local infiltration analgesia.
      Female sex is a factor that has not previously been associated with peak
      ropivacaine concentrations.

PMID- 29369958
TI  - Epidural Hematoma Following Cessation of a Direct Oral Anticoagulant: A Case
      Report.
AB  - OBJECTIVE: In this case report, we describe a case of epidural hematoma following
      epidural analgesia in a patient with recent cessation of a direct oral
      anticoagulant (DOAC). CASE REPORT: An 89-year-old woman requiring upper abdominal
      surgery presented with multiple comorbidities, including a prior cerebrovascular
      accident resulting in a left-sided hemiparesis and atrial fibrillation requiring
      anticoagulation with rivaroxaban. In accordance with our departmental guidelines
      at the time of procedure, rivaroxaban was discontinued 4 days preoperatively. A
      thoracic epidural was placed at T8/9 immediately prior to induction. Venous
      thromboembolism prophylaxis was provided with compression devices, and every-12
      hour unfractionated heparin initiated 5.5 hours after epidural placement. On
      postoperative day 2, the patient was noted to have a bilateral motor block, and
      imaging demonstrated a thoracic epidural hematoma extending from T6 to T11.
      Preexisting neurological deficits may have delayed detection. With patient
      agreement, neurosurgery recommended observation rather than surgical
      decompression because the patient was a poor surgical candidate and limited
      neurologic recovery was expected. The patient had modest motor recovery over the
      next few months. CONCLUSIONS: Guidelines for cessation of DOACs prior to
      neuraxial techniques are based on pharmacologic half-lives rather than
      accumulated experience. This case adds to the experience of neuraxial analgesia
      complications while following these guidelines. Patient risk may be increased by
      the combination of recent cessation of a DOAC, as well as the cumulative effect
      of multiple small risk factors. Continued vigilance and reporting of cases of
      epidural hematomas will enhance our understanding and ultimately improve patient
      care. Elderly patients and/or patients with prior neurological deficits may
      present further challenges for early detection and require frequent assessments
      with comparison to baseline status.

PMID- 29369960
TI  - Risk of Acute Ischemic Stroke in Patients With Monocular Vision Loss of Vascular
      Etiology.
AB  - BACKGROUND: To evaluate the risk of concurrent acute ischemic stroke and
      monocular vision loss (MVL) of vascular etiology. DESIGN: Retrospective, cross
      sectional study. SUBJECTS: Patients aged 18 or older diagnosed with MVL of
      suspected or confirmed vascular etiology who had no other neurologic deficits and
      who received brain MRI within 7 days of onset of visual symptoms were included.
      METHODS: A medical record review was performed from 2013 to 2016 at Yale New
      Haven Hospital. Patients were included if vision loss was unilateral and due to
      transient monocular vision loss (TMVL), central retinal artery occlusion (CRAO),
      or branch retinal artery occlusion (BRAO). Any patients with neurologic deficits
      other than vision loss were excluded. Other exclusion criteria were positive
      visual phenomena, nonvascular intraocular pathology, and intracranial pathology
      other than ischemic stroke. MAIN OUTCOME MEASURES: The presence or absence of
      acute stroke on diffusion-weighted imaging (DWI) on brain MRI. RESULTS: A total
      of 641 records were reviewed, with 293 patients found to have MVL. After
      excluding those with focal neurologic deficits, there were 41 patients who met
      the inclusion criteria and received a brain MRI. Eight of the 41 subjects (19.5%)
      were found to have findings on brain MRI positive for acute cortical strokes. The
      proportion of lesion positive MRI was 1/23 (4.3%) in TMVL subjects, 4/12 (33.3%)
      in CRAO subjects, and 2/5 (40%) in BRAO subjects. Brain computed tomography (CT)
      scans were not able to identify the majority of acute stroke lesions in this
      study. CONCLUSIONS: Patients with MVL of vascular etiology such as TMVL, CRAO, or
      BRAO may have up to 19.5% risk of concurrent ischemic stroke, even when there are
      no other neurologic deficits. These strokes were detected acutely with brain MRI
      using DWI but were missed on CT.

PMID- 29369961
TI  - Role of Scientific Theory in Simulation Education Research.
AB  - STATEMENT: Scientific theories are consistent explanations about how the world
      works. They have been shown to be plausible not only from a large amount of
      independent confirmatory evidence but also because rigorous attempts at
      falsification have failed. Other desirable features include parsimony,
      scalability, explanatory, and predictive power. Scientific theories differ from
      models and laws in the amount of evidence available and/or the degree to which
      they explain nature. Learning curve theory is a scientific theory with direct
      applicability to simulation education researchers. In this article, the authors
      use the example of learning curve theory to illustrate the key features of
      scientific theories and how they provide a meaningful foundation for simulation
      based education research programs.

PMID- 29369962
TI  - Establishing a Virtual Community of Practice in Simulation: The Value of Social
      Media.
AB  - STATEMENT: Professional development opportunities are not readily accessible for
      most simulation educators, who may only connect with simulation experts at
      periodic and costly conferences. Virtual communities of practice consist of
      individuals with a shared passion who communicate via virtual media to advance
      their own learning and that of others. A nascent virtual community of practice is
      developing online for healthcare simulation on social media platforms. Simulation
      educators should consider engaging on these platforms for their own benefit and
      to help develop healthcare simulation educators around the world. Herein, we
      describe this developing virtual community of practice and offer guidance to
      assist educators to engage, learn, and contribute to the growth of the community.

PMID- 29369963
TI  - Comparison of Cardiopulmonary Resuscitation Quality Between Standard Versus
      Telephone-Basic Life Support Training Program in Middle-Aged and Elderly
      Housewives: A Randomized Simulation Study.
AB  - INTRODUCTION: For cardiac arrests witnessed at home, the witness is usually a
      middle-aged or older housewife. We compared the quality of cardiopulmonary
      resuscitation (CPR) performance of bystanders trained with the newly developed
      telephone-basic life support (T-BLS) program and those trained with standard BLS
      (S-BLS) training programs. METHODS: Twenty-four middle-aged and older housewives
      without previous CPR education were enrolled and randomized into two groups of
      BLS training programs. The T-BLS training program included concepts and current
      instruction protocols for telephone-assisted CPR, whereas the S-BLS training
      program provided training for BLS. After each training course, the participants
      simulated CPR and were assisted by a dispatcher via telephone. Cardiopulmonary
      resuscitation quality was measured and recorded using a mannequin simulator. The
      primary outcome was total no-flow time (>1.5 seconds without chest compression)
      during simulation. RESULTS: Among 24 participants, two (8.3%) who experienced
      mechanical failure of simulation mannequin and one (4.2%) who violated simulation
      protocols were excluded at initial simulation, and two (8.3%) refused follow-up
      after 6 months. The median (interquartile range) total no-flow time during
      initial simulation was 79.6 (66.4-96.9) seconds for the T-BLS training group and
      147.6 (122.5-184.0) seconds for the S-BLS training group (P < 0.01). Median
      cumulative interruption time and median number of interruption events during BLS
      at initial simulation and 6-month follow-up simulation were significantly shorter
      in the T-BLS than in the S-BLS group (1.0 vs. 9.5, P < 0.01, and 1.0 vs. 10.5, P
      = 0.02, respectively). CONCLUSIONS: Participants trained with the T-BLS training
      program showed shorter no-flow time and fewer interruptions during bystander CPR
      simulation assisted by a dispatcher.

PMID- 29369964
TI  - Laparoscopic Hilar Lymph Node Sampling in Patients With Biliary Tract Cancers
      That are Rarely Associated With Nodal Metastasis.
AB  - PURPOSE: Among the various types of biliary tract cancer, patients with single,
      small (<5 cm), peripheral intrahepatic cholangiocarcinoma (ICC), or small (<2 cm)
      gallbladder tumors (GBTs) rarely develop lymph node (LN) metastasis. We
      investigated a laparoscopic approach for hilar LN sampling in such cases.
      METHODS: Among the 176 patients with biliary tract cancer who were treated from
      January 2012 to March 2017, 21 (ICC, n=4; GBT, n=17) met the above indications.
      RESULTS: All patients were treated by a laparoscopic approach with R0 resection.
      After determining the pathologic diagnosis, 9 patients with GBT and all 4
      patients with ICC underwent laparoscopic LN sampling; the mean numbers of sampled
      LNs were 2.6 and 7.3, respectively; no patients had metastasis. The mean
      operating times for GBT and ICC were 223 and 379 minutes, respectively; the mean
      blood loss was 23 mL and 171 mL. With the exception of 1 patient who developed
      intrahepatic metastasis of ICC at the opposite liver lobe, all of the patients
      were recurrence free. CONCLUSIONS: A laparoscopic approach could be safely
      applied under our indications.

PMID- 29369965
TI  - Impact of Surgeon's Surgical Experience on Outcomes After Laparoscopic Distal
      Gastrectomy in High Body Mass Index Patients.
AB  - The aim of this study was to evaluate the impact of surgical experience on
      laparoscopic distal gastrectomy in high body mass index (BMI) patients.
      Retrospective data were collected on patients who underwent laparoscopic distal
      gastrectomy for early gastric cancer from July 2002 to December 2014. Patients
      were divided into a high BMI group (BMI>=25 kg/m) and a low BMI group (BMI<25
      kg/m) and classified into subgroups by surgeon experience. Patient
      characteristics and surgical outcomes between groups were analyzed and compared.
      Mean operation time in the high BMI group was longer than the low BMI group
      (173.0+/-52.5 vs. 164.2+/-48.0 min; P=0.009). Subgroup analysis showed longer
      operation time in the high BMI group than the low BMI group (200.8+/-49.3 vs.
      187.9+/-45.2 min; P<0.001) and fewer retrieved lymph nodes (36.3+/-11.7 vs.
      33.0+/-13.1; P=0.004) in the early surgeon experience period. Patients in the
      late experience period showed no significant differences in surgical outcomes
      between the high BMI and low BMI group. High BMI did not influence surgical
      outcomes of laparoscopic distal gastrectomy after accumulation of surgical
      experience.

PMID- 29369968
TI  - Quantitative sensory test correlates with neuropathy, not with pain.

PMID- 29369967
TI  - Lateralized kappa opioid receptor signaling from the amygdala central nucleus
      promotes stress-induced functional pain.
AB  - The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or
      lost, in stress-related functional pain syndromes. Because the dynorphin/kappa
      opioid receptor (KOR) pathway is activated by stress, we determined its role in
      DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats
      were primed for 7 days with systemic morphine resulting in opioid-induced
      hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats
      were exposed to environmental stress and DNIC was evaluated by measuring hind paw
      response threshold to noxious pressure (test stimulus) after capsaicin injection
      in the forepaw (conditioning stimulus). Morphine priming without stress did not
      alter DNIC. However, stress produced a loss of DNIC in morphine-primed rats in
      both hind paws that was abolished by systemic administration of the KOR
      antagonist, nor-binaltorphimine (nor-BNI). Microinjection of nor-BNI into the
      right, but not left, central nucleus of the amygdala (CeA) prevented the loss of
      DNIC in morphine-primed rats. Diffuse noxious inhibitory controls were not
      modulated by bilateral nor-BNI in the rostral ventromedial medulla. Stress
      increased dynorphin content in both the left and right CeA of primed rats,
      reaching significance only in the right CeA; no change was observed in the
      rostral ventromedial medulla or hypothalamus. Although morphine priming alone is
      not sufficient to influence DNIC, it establishes a state of latent sensitization
      that amplifies the consequences of stress. After priming, stress-induced
      dynorphin/KOR signaling from the right CeA inhibits DNIC in both hind paws,
      likely reflecting enhanced descending facilitation that masks descending
      inhibition. Kappa opioid receptor antagonists may provide a new therapeutic
      strategy for stress-related functional pain disorders.

PMID- 29369969
TI  - The Long Journey of mTOR Inhibitors and the Long Path That Is Still Ahead.

PMID- 29369966
TI  - Orally active Epac inhibitor reverses mechanical allodynia and loss of
      intraepidermal nerve fibers in a mouse model of chemotherapy-induced peripheral
      neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of
      cancer treatment that significantly compromises quality of life of cancer
      patients and survivors. Identification of targets for pharmacological
      intervention to prevent or reverse CIPN is needed. We investigated exchange
      protein regulated by cAMP (Epac) as a potential target. Epacs are cAMP-binding
      proteins known to play a pivotal role in mechanical allodynia induced by nerve
      injury and inflammation. We demonstrate that global Epac1-knockout (Epac1-/-)
      male and female mice are protected against paclitaxel-induced mechanical
      allodynia. In addition, spinal cord astrocyte activation and intraepidermal nerve
      fiber (IENF) loss are significantly reduced in Epac1-/- mice as compared to wild
      type mice. Moreover, Epac1-/- mice do not develop the paclitaxel-induced deficits
      in mitochondrial bioenergetics in the sciatic nerve that are a hallmark of CIPN.
      Notably, mice with cell-specific deletion of Epac1 in Nav1.8-positive neurons (N
      Epac1-/-) also show reduced paclitaxel-induced mechanical allodynia, astrocyte
      activation, and IENF loss, indicating that CIPN develops downstream of Epac1
      activation in nociceptors. The Epac-inhibitor ESI-09 reversed established
      paclitaxel-induced mechanical allodynia in wild-type mice even when dosing
      started 10 days after completion of paclitaxel treatment. In addition, oral
      administration of ESI-09 suppressed spinal cord astrocyte activation in the
      spinal cord and protected against IENF loss. Ex vivo, ESI-09 blocked paclitaxel
      induced abnormal spontaneous discharges in dorsal root ganglion neurons.
      Collectively, these findings implicate Epac1 in nociceptors as a novel target for
      treatment of CIPN. This is clinically relevant because ESI-09 has the potential
      to reverse a debilitating and long-lasting side effect of cancer treatment.

PMID- 29369970
TI  - mTOR Inhibition Role in Cellular Mechanisms.
AB  - The mammalian target of rapamycin inhibitors (mTOR-I), drugs widely used in
      transplant medicine and oncology, exert their function by inhibiting a
      serine/threonine kinase with a pivotal role in cellular metabolism and in a wide
      range of eukaryotic biological/cellular functions and signaling networks.
      Additionally, as largely described, the inhibition of mTOR has a major impact on
      cellular metabolism by stimulating synthesis of proteins and lipids, inhibiting
      catabolic processes, such as lysosome biogenesis and autophagy, and controlling
      cell survival, cytoskeleton organization, lipogenesis, and gluconeogenesis. All
      these biological functions are essential to guarantee body homeostasis and
      survival. Therefore, it is necessary for clinicians and researchers to better
      understand this complex pathway to ameliorate patients' treatment empathizing
      therapeutic effects to minimize/avoid toxicities and to propose new valuable
      research strategies.The aim of this article has been to underline the complexity
      of the mTOR pathway and to review the recent literature describing the
      consequences of its inhibition on several cellular functions including (a)
      protein synthesis, (b) cell cycle,

PMID- 29369971
TI  - mTOR Inhibition and Clinical Transplantation: Heart.
AB  - This brief overview discusses recent data on the use of mammalian target of
      rapamycin (mTOR) inhibitors in heart transplantation. Trials on de novo use have
      shown good efficacy of mTOR inhibitors; however, adverse events are often seen.
      Conversion protocols in long-term patients are mainly used in patients with renal
      insufficiency. Calcineurin inhibitor minimization and conversion to calcineurin
      inhibitor-free protocols have proven to stabilize renal function in recent
      trials. Lastly, beneficial effects of mTORs against the development of graft
      vasculopathy, cytomeglovirus infection and malignancy have been shown.
      Nevertheless, lower tolerability of the drug has affected the long-term use in
      patients. Future consideration of using mTORs will be individualized protocols in
      special subpopulation after heart transplantation.

PMID- 29369972
TI  - mTOR Inhibition and Kidney Diseases.
AB  - Mammalian or mechanistic target of rapamycin (mTOR) is a serine-threonine kinase
      that plays essential roles in cell growth, proliferation, metabolism, and
      survival. Increased activation of the mTOR pathway is observed in patients and
      animal models of renal transplant rejection, autosomal dominant polycystic kidney
      disease, renal cell carcinoma, diabetic nephropathy, lupus nephritis, and
      angiomyolipoma. Agents that inhibit mTOR, such as sirolimus and everolimus, are
      incorporated in immunosuppressive regimens to prevent renal allograft rejection
      and are often used to facilitate calcineurin inhibitor minimization or to reduce
      the incidence of tumor recurrence. There are data from basic or animal studies to
      suggest that sirolimus and its analogs may also benefit patients with autosomal
      dominant polycystic kidney disease and metabolic- or immune-mediated renal
      diseases through its ability to reduce glomerular hypertrophy, renal parenchymal
      inflammation and fibrosis, but translation into clinical use has proved
      challenging. This review summarizes the current understanding of mTOR signaling
      pathway under physiological and pathological conditions and recent findings on
      mTOR inhibitors in the management of kidney transplantation and nontransplant
      kidney diseases.

PMID- 29369973
TI  - The Role of mTOR Inhibitors in the Management of Viral Infections: A Review of
      Current Literature.
AB  - Viruses are the leading cause of infections after solid organ transplant. The
      antiviral properties of mammalian target of rapamycin inhibitors (mTORis) have
      been ascribed to a variety of mechanisms and historical data have supported their
      use over other immunosuppressants for a myriad of viruses. Herein, we summarize
      the most current data to highlight the role of mTORis in the management of viral
      infections after solid organ transplant. The mTORis play a clear role in the
      management of cytomegalovirus, and have data supporting their potential use for
      BK virus and human herpesvirus 8-related Kaposi sarcoma. No data definitively
      supports mTORis for use in Epstein-Barr virus-mediated posttransplant
      lymphoproliferative disorder or hepatitis C virus viral replication. Although
      theoretically an advantageous therapy for hepatitis C virus-related liver
      allograft fibrosis and human immunodeficiency virus, mTORi use specifically for
      these indications is less attractive with modern treatments currently available.
      Data surrounding mTORi efficacy in preventing rejection, and their toxicity
      profile must be balanced with their potential antiviral effects in combination
      with patient-specific factors.

PMID- 29369974
TI  - Therapeutic Drug Monitoring of Second-Generation Antipsychotics for the
      Estimation of Early Drug Effect in First-Episode Psychosis: A Cross-sectional
      Assessment.
AB  - BACKGROUND: Studies on therapeutic drug monitoring (TDM) of second-generation
      antipsychotics (SGAs) have provided conflicting results regarding the association
      between dose, plasma concentrations, and drug effect and have focused rather on
      analyzing how individual drugs work. No study has attempted to process data from
      different SGAs globally to offer a panoramic view of the utility of TDM in
      clinical practice, and data on patients with first-episode psychosis (FEP) are
      lacking. This study aimed to assess the relationship between dose, plasma
      concentrations, and drug effect in a sample of patients with FEP, regardless of
      the SGA prescribed. METHODS: Data from 64 compliant patients treated with the
      same SGA during a 2-month follow-up were recorded. Clinical symptoms were
      assessed using the Positive and Negative Symptoms Scale and the Montgomery-Asberg
      Depression Rating Scale. Adverse effects were rated using the Udvalg fur Kliniske
      Undersogelser scale. SGA doses were standardized to chlorpromazine equivalents,
      and patients were classified into 3 different ranges according to their plasma
      concentrations (subtherapeutic, therapeutic, and supratherapeutic). RESULTS:
      Plasma concentration ranges were proportionally related to dose. Patients with
      supratherapeutic plasma concentrations were treated with doses significantly
      higher than those with subtherapeutic concentrations. Dose and plasma
      concentrations were not associated with early drug effect. CONCLUSIONS: TDM seems
      unable to accurately estimate the early effects of SGAs in FEP. Ours is the first
      study to categorize plasma concentrations of SGAs into ranges for joint
      processing of data from a larger number of patients.

PMID- 29369975
TI  - Laughter Is the Best Medicine: Teaching to Teach Using Standardized Patients.
AB  - This article describes an innovative approach to patient teaching using
      standardized patients, humor, and therapeutic communication. The strategy was
      designed for baccalaureate students enrolled in a fundamentals nursing course.
      Students, divided into small groups, were assigned a patient education topic to
      provide to the standardized patient. Student and faculty feedback indicated
      positive responses to this instructional strategy. Utilization of this learner
      centered teaching environment to promote therapeutic communication during a
      complex patient-teaching scenario was found to be beneficial for novice nursing
      students.

PMID- 29369976
TI  - Direct-to-Implant Breast Reconstruction in Women Older than 65 Years: A
      Retrospective Analysis of Complication Rate and Overall Outcomes.
AB  - BACKGROUND: Half of all cancers occur in women older than 65 years, yet only 4 to
      14 percent of these women undergo reconstruction. Most studies on reconstruction
      in the elderly have focused on tissue expander/implant or autologous
      reconstruction. A direct-to-implant approach theoretically reduces the number of
      operations and postoperative visits, but has yet to be investigated in the
      elderly. METHODS: Institutional review board approval was granted for a
      retrospective chart review for patients who underwent direct-to-implant
      reconstruction from 2012 to 2015 with any staff in the authors' department. A
      control cohort of patients who underwent tissue expander/implant-based
      reconstruction from the same period was analyzed. RESULTS: Direct-to-implant
      reconstruction was performed in 24 breasts in 19 patients with at least 30-day
      follow-up and in 17 breasts in 14 patients with at least 1-year follow-up. A
      control group analysis of tissue expander/implant patients was performed for 109
      breasts in 88 patients. The tissue expander/implant group was significantly
      younger (p = 0.001), with a lower body mass index (p = 0.004). There was no
      difference in the rate of seroma, hematoma, infection, necrosis, or failed
      reconstruction. Direct-to-implant patients had significantly reduced numbers of
      drain days (p < 0.001), length of stay (p = 0.05 and p = 0.039), readmissions (p
      = 0.03 and 0.03), extra hospital days (p = 0.05 and p = 0.045), and postoperative
      visits (p < 0.001). CONCLUSIONS: Direct-to-implant breast reconstruction in the
      elderly yields similar complication and failure rates compared to tissue
      expander/implant reconstruction. However, direct-to-implant reconstruction
      patients had a reduced number of drain days and fewer readmissions, hospital
      stays, and postoperative visits. Direct-to-implant reconstruction is a powerful
      tool to use in elderly women with appropriate breast shape and ptosis. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29369977
TI  - Discussion: The Lateral Thigh Perforator Flap for Autologous Breast
      Reconstruction: A Prospective Analysis of 138 Flaps.

PMID- 29369978
TI  - Venous Superdrainage in DIEP Flap Breast Reconstruction: The Impact of
      Superficial Inferior Epigastric Vein Dissection on Abdominal Seroma Formation.
AB  - BACKGROUND: Abdominal seroma formation after deep inferior epigastric perforator
      (DIEP) flap breast reconstruction is a common donor-site complication. Additional
      dissection of one or both of the superficial inferior epigastric veins (SIEVs) in
      DIEP flap breast reconstruction allows an additional anastomosis for venous
      superdrainage if venous congestion occurs. However, generally, SIEV dissection
      involves greater invasiveness into the inguinal region, which can traumatize
      lymphatic tissue and lead to lymph accumulation. The aim of this study was to
      evaluate the impact of SIEV dissection on the incidence of postoperative
      abdominal seroma. METHODS: A series of 100 consecutive cases performed by the
      Department of Plastic and Reconstructive Surgery at the Medical University of
      Vienna from 2001 to 2016 was analyzed. Patients were divided into three groups:
      unilateral, bilateral, and no SIEV dissection. Abdominal seroma rates, length of
      hospital stay, abdominal drainage duration, and drainage fluid volumes were
      compared retrospectively. RESULTS: Seromas were observed in 11.5 percent of
      patients without SIEV dissection, 17.2 percent of patients with unilateral SIEV
      dissection (p = 0.45 versus no SIEV), and 40 percent of patients with bilateral
      SIEV dissection (p = 0.02 versus no SIEV). The SIEV was anastomosed to salvage a
      congested DIEP flap twice. All seromas that developed could be treated with, on
      average, two fine-needle aspirations without any complications. CONCLUSIONS:
      Bilateral, but not unilateral, SIEV dissection increased abdominal seroma rates
      significantly. Venous congestion was observed rarely, but when it did occur, it
      endangered flap viability. Because an additional anastomosis of the SIEV can
      salvage a flap, unilateral SIEV dissection should be considered when raising a
      DIEP flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29369979
TI  - The Comparison of Strattice and SurgiMend in Acellular Dermal Matrix-Assisted,
      Implant-Based Immediate Breast Reconstruction.
AB  - BACKGROUND: Strattice (porcine derivative) and SurgiMend (bovine derivative) are
      the two most common acellular dermal matrices used in breast reconstruction in
      the United Kingdom. This retrospective study compared clinical outcomes in
      immediate implant-based breast reconstruction patients. METHODS: The study,
      conducted across three hospitals, included all patients who underwent immediate
      implant-based breast reconstruction using Strattice and SurgiMend. The primary
      outcome measure was implant loss rate. Secondary outcome measures included
      acellular dermal matrix loss rate, seroma formation, and minor and major
      complication rates. Intergroup comparison was performed. RESULTS: Eighty-two
      patients (Strattice, n = 45; SurgiMend, n = 37) underwent 97 immediate implant
      based breast reconstructions (Strattice, n = 54; SurgiMend, n = 43). There were
      no differences between groups for age, comorbidities, specimen weight, or implant
      volume. Drains were used in all Strattice and 36 (84 percent) SurgiMend cases.
      The implant loss rate was higher for Strattice (n = 10, 20 percent) compared with
      SurgiMend (n = 3, 7 percent) but failed to reach statistical significance (chi
      square test, p = 0.077). The acellular dermal matrix loss rate was significantly
      higher (Fisher's exact test, p = 0.014) in the Strattice group (n = 7, 14
      percent), with no acellular dermal matrix loss with SurgiMend. The reoperation
      rate was also significantly higher (chi-square test, p = 0.002) in the Strattice
      group (n = 17, 33 percent, versus n = 3, 7 percent). The incidence of red breast
      was significantly higher (chi-square test, p = 0.022) in the SurgiMend group (n =
      9, 21 percent, versus n = 3, 6 percent). Seroma, wound problems, and infection
      rates were similar. CONCLUSIONS: Clinical outcomes, including implant loss,
      acellular dermal matrix loss, and reoperation rates, are significantly better
      when using SurgiMend in immediate implant-based breast reconstruction compared
      with Strattice. An appropriately powered randomized trial is needed to provide
      further information. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 29369980
TI  - Conceptual Considerations for Payment Bundling in Breast Reconstruction.
AB  - Rising health care costs and quality demands have driven both the Centers for
      Medicare and Medicaid Services and the private sector to seek innovations in
      health system design by placing institutions at financial risk. Novel care
      models, such as bundled reimbursement, aim to boost value though quality
      improvement and cost reduction. The Center for Medicare and Medicaid Innovation
      is leading the charge in this area with multiple pilots and mandates, including
      Comprehensive Care for Joint Replacement. Other high-cost and high-volume
      procedures could be considered for bundling in the future, including breast
      reconstruction. In this article, conceptual considerations surrounding bundling
      of breast reconstruction are discussed.

PMID- 29369981
TI  - Discussion: Conceptual Considerations for Payment Bundling in Breast
      Reconstruction.

PMID- 29369982
TI  - Introducing the PRS Video Vignette Masters Series.

PMID- 29369983
TI  - Gluteal Augmentation and Enhancement of the Female Silhouette: Analysis and
      Technique.
AB  - Dr. Constantino Mendieta demonstrates and details his personal technique for
      gluteal augmentation. The video demonstration is divided into three parts: Part
      I, Aesthetic Analysis and Preoperative Marking; Part II, Creating the Female
      Silhouette with Circumferential Lipoplasty; and Part III, Autogenous Gluteal
      Augmentation. Artistic concepts for gluteal augmentation and contouring the
      female silhouette and technical considerations for patient safety are emphasized.
      This Master Series Video article is the first in a planned series of video
      vignettes.

PMID- 29369984
TI  - Orthognathic Surgery and Rhinoplasty: Simultaneous or Staged?
AB  - BACKGROUND: Orthognathic surgery can significantly impact the nasolabial
      envelope, and at times requires an adjunctive rhinoplasty. The purpose of this
      study was to evaluate nasal morphology in orthognathic patients, focusing on
      predictive variables, and the need for and timing of definitive rhinoplasty.
      Based on these data, an algorithm for the implementation of adjunctive
      rhinoplasty is proposed. METHODS: A review of cases over a 3-year period was
      completed. Information regarding demographic, diagnostic, and operative details;
      nasal morphology; and use of rhinoplasty was compiled. Three-dimensional images
      were used to quantify anatomical variables. RESULTS: Over 589 patients were
      reviewed during this period. Of these, 163 fulfilled inclusion criteria for this
      study. The mean age was 23.3 years. In total, 41.7 percent of orthognathic cases
      underwent adjunctive rhinoplasty. Of these, 82.4 percent were staged and 17.6
      percent were simultaneous. The average time between staged procedures was 208
      days. When simultaneous, 16.7 percent of the orthognathic procedures had
      significant maxillary movement (advancement >4 to 5 mm, impaction >2 mm, alar
      base excisions); in comparison, 92.9 percent of staged cases had significant
      maxillary movement (p < 0.0001). All patients had self-reported satisfaction with
      functional and aesthetic results during the follow-up period. CONCLUSIONS: Nasal
      and jaw deformities are intricately interlinked. In this series, the authors
      identified patterns requiring adjunctive rhinoplasty in the setting of
      orthognathic surgery. The authors present an algorithm to extensively treat the
      nasomaxillofacial relationship using orthognathic surgery alone, orthognathic
      surgery in concert with rhinoplasty, or orthognathic surgery followed by staged
      rhinoplasty.

PMID- 29369985
TI  - External Levator Advancement versus Muller Muscle-Conjunctival Resection for
      Aponeurotic Blepharoptosis: A Randomized Clinical Trial.
AB  - BACKGROUND: The purpose of this study was to compare the efficacy of external
      levator advancement and Muller muscle-conjunctival resection in aponeurotic
      blepharoptosis repair. METHODS: Mild to moderate blepharoptosis patients with
      good levator function and a positive phenylephrine test were randomized to upper
      blepharoplasty with either external levator advancement or Muller muscle
      conjunctival resection. The primary outcome was marginal reflex distance 1 at 1
      month after surgery. Secondary outcomes were cosmetic outcome, complications, and
      operating room time. RESULTS: Forty patients were enrolled, six men and 34 women,
      with an average age of 62.4 years. The mean preoperative marginal reflex distance
      1 in the levator group (39 eyes/20 subjects) and the Muller group (38 eyes/20
      subjects) was 1.2 +/- 0.8 mm and 1.5 +/- 0.7 mm, respectively. The mean
      postoperative marginal reflex distance 1 in the levator and Muller groups was 3.0
      +/- 1.0 mm and 3.2 +/- 1.0 mm, respectively. The difference in the mean change
      was 0.008, and was not statistically different (95 percent CI, -0.59 to 0.61; p =
      0.978). The mean cosmetic outcome was 2.69 +/- 0.81 for the levator group and
      3.07 +/- 0.68 for the Muller group, with a mean difference of 0.373 (95 percent
      CI, 0.06 to 0.69; p = 0.020). The average operating room time was 75 +/- 19.2
      minutes for the levator group and 71 +/- 23.6 minutes for the Muller group (p =
      0.439). There were four eyes that underwent reoperation, three in the levator
      group (7.7 percent) and one in the Muller group (2.6 percent). CONCLUSIONS:
      External elevator advancement and Muller muscle-conjunctival resection are both
      effective in correction of mild to moderate blepharoptosis. However, Muller
      muscle-conjunctival resection yields a statistically significant better cosmetic
      outcome and causes less eyelid asymmetry. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, II.

PMID- 29369987
TI  - Discussion: Outcomes after Phalloplasty: Do Transgender Patients and Multiple
      Urethral Procedures Carry a Higher Rate of Complication?

PMID- 29369986
TI  - Postbariatric Brachioplasty with Posteromedial Scar: Physical Model, Technical
      Refinements, and Clinical Outcomes.
AB  - BACKGROUND: Brachioplasty is an increasingly performed procedure following
      massive weight loss. A visible scar is the main hindrance to this surgery. The
      aims of the study were to develop a physical model to investigate the ideal
      location of the surgical incision and to present the authors' technical
      refinements with the posteromedial scar approach. METHODS: Twenty-four
      postbariatric patients underwent brachioplasty with posteromedial scar placement,
      concomitant liposuction, fascial plication, and axillary Z-plasty. Skin specimens
      were tested and a physical model of the arm was set up to investigate the
      difference in mechanical stress on the posteromedial and medial scars. The
      validated Patient and Observer Scar Assessment Scale, the Vancouver Scar Scale,
      and a questionnaire assessing subjective improvements were administered to
      patients. Preoperative and postoperative photographs were assessed by three
      independent plastic surgeons. RESULTS: The physical model showed that stress
      intensity and distribution along the scar were reduced in the posteromedial
      location, with smaller scar displacement in the loading simulations. Twenty-three
      patients healed uneventfully. One (4.1 percent) had a 2-cm dehiscence. Mean
      Patient and Observer Scar Assessment Scale scores were, respectively, 2 +/- 0.76
      and 2.13 +/- 0.64 in the patients' and observers' questionnaires. The mean
      Vancouver Scar Scale value was 3.5 +/- 1.7. Questionnaires assessing the
      subjective outcomes showed a mean value of 3.45 +/- 0.63 of 4. The surgeons'
      assessment resulted in a score of 4.5 +/- 0.4 of 5. CONCLUSIONS: The physical
      model demonstrated that the posteromedial scar was subjected to lower mechanical
      stress and displacement. The reported technical refinements allowed pleasant arm
      recontouring to be achieved with acceptable scarring and a low incidence of
      complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 29369988
TI  - The Keystone: Consistency in Restoring the Aesthetic Dorsum in Rhinoplasty.
AB  - The keystone represents the union of six distinct anatomical structures between
      the bony vault and the cartilaginous midvault. In reshaping the nasal dorsum, the
      individual components of the nose respond variably as the fusion points of the
      keystone are released. In restoring the nasal dorsum, meticulous effort is made
      to equalize the width between the bony vault and the cartilaginous midvault.
      Techniques used for width equalization will yield gratifying long-term results
      and avoid common pitfalls such as the inverted-V deformity.

PMID- 29369989
TI  - Discussion: Early Macrophage Infiltration Improves Fat Graft Survival by Inducing
      Angiogenesis and Hematopoietic Stem Cell Recruitment.

PMID- 29369990
TI  - Effect of Cryopreservation on Human Adipose Tissue and Isolated Stromal Vascular
      Fraction Cells: In Vitro and In Vivo Analyses.
AB  - BACKGROUND: Adipose tissue is a source of adipose-derived stromal/stem cells for
      tissue engineering and reconstruction and a tissue source for fat grafts.
      Although liposuction is a simple procedure for the harvest of adipose tissue, the
      repetition of this surgical intervention can cause adverse effects to the patient
      and can be a limiting factor for immediate use. Cryopreservation can avoid the
      morbidity associated with repetitive liposuction, allowing the use of stored
      tissue after the initial harvest procedure. This article focuses on the
      characterization of fresh and cryopreserved human adipose tissue. METHODS:
      Lipoaspirates from eight donors were processed as fresh adipose tissue or
      cryopreserved for 4 to 6 weeks. Fresh and cryopreserved tissues were collagenase
      digested and the stromal vascular fraction cells were characterized immediately
      or cryopreserved. Characterization was based on stromal vascular fraction cell
      proliferation and immunophenotype. In vivo fat grafting was performed in C57BL/6
      green fluorescent protein mice to analyze morphology of the tissue and its
      adiposity using confocal microscopy, histochemical staining (i.e., hematoxylin
      and eosin and Masson trichrome), and immunohistochemistry (i.e., green
      fluorescent protein, perilipin, and CD31). RESULTS: Although tissue and stromal
      vascular fraction cell cryopreservation reduced the total cell yield, the
      remaining viable cells retained their adhesive and proliferative properties. The
      stromal vascular fraction cell immunophenotype showed a significant reduction in
      the hematopoietic surface markers and increased expression of stromal and
      adipogenic markers following cryopreservation. In vivo cryopreserved fat grafts
      showed morphology similar to that of freshly implanted fat grafts. CONCLUSION: In
      this study, the authors demonstrated that cryopreserved adipose tissue is a
      potential source of stromal vascular fraction cells and a suitable source for fat
      grafts.

PMID- 29369991
TI  - Conditioned Medium Obtained from Amnion-Derived Mesenchymal Stem Cell Culture
      Prevents Activation of Keloid Fibroblasts.
AB  - BACKGROUND: Mesenchymal stem cells are a valuable cell source in regenerative
      medicine, and conditioned medium obtained from mesenchymal stem cells reportedly
      inhibits inflammation. Keloids are characterized by abnormal fibrosis, caused by
      fibroblasts in response to inflammation. In this study, the authors evaluated
      whether conditioned medium obtained from amnion-derived mesenchymal stem cells
      suppressed activation of keloid fibroblasts. METHODS: Keloid (n = 7), mature (n =
      5), and normal (n = 5) fibroblasts were harvested from patients. Fibroblasts were
      stimulated with transforming growth factor (TGF)-beta, and the effects of
      conditioned medium obtained from amnion-derived mesenchymal stem cells on cell
      proliferation, activation, and expression of extracellular matrix-related genes
      were analyzed. The effect of concentrating the conditioned medium by
      ultrafiltration on fibroblast activation was also analyzed. RESULTS: Conditioned
      medium obtained from amnion-derived mesenchymal stem cells significantly up
      regulated proliferation of mature fibroblasts but tended to suppress that of
      keloid fibroblasts. Conditioned medium obtained from amnion-derived mesenchymal
      stem cells significantly suppressed the TGF-beta-induced up-regulation of alpha
      smooth muscle actin in keloid and normal fibroblasts and collagen I in keloid
      fibroblasts, but not in mature fibroblasts. The conditioned medium obtained from
      amnion-derived mesenchymal stem cells concentrated by ultrafiltration and the
      filtrate significantly suppressed TGF-beta-induced alpha-smooth muscle actin
      expression. CONCLUSION: Conditioned medium obtained from amnion-derived
      mesenchymal stem cells prevents proliferation and activation of keloid
      fibroblasts and is a promising keloid treatment for administration as a topical
      agent. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 29369992
TI  - Discussion: Important Details in Performing and Interpreting the Scratch Collapse
      Test.

PMID- 29369993
TI  - Discussion: Appropriateness of the Use of Magnetic Resonance Imaging in the
      Diagnosis and Treatment of Wrist Soft Tissue Injury.

PMID- 29369994
TI  - Discussion: Minimally Invasive, Spring-Assisted Correction of Sagittal Suture
      Synostosis: Technique, Outcome, and Complications in 83 Cases.

PMID- 29369995
TI  - Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a Link between
      Inflammatory Signaling and Osteoclast Activation in Human Cranial Suture Patency.
AB  - BACKGROUND: The pathophysiology of nonsyndromic craniosynostosis remains poorly
      understood. The authors seek to understand the cause of this condition with a
      specific focus on how osteoclasts may contribute to craniosynostosis. Here, the
      authors characterize proteins differentially expressed in patent and fused
      cranial sutures by comparing their respective proteomes. METHODS: Fused and
      patent suture samples were obtained from craniosynostotic patients undergoing
      surgery at a single academic medical center. Extracted protein from samples was
      interrogated using mass spectrometry. Differential protein expression was
      determined using maximum likelihood-based G-test with a q-value cutoffs of 0.5
      after correction for multiple hypothesis testing. Immunolocalization of lead
      protein candidates was performed to validate proteomic findings. In addition,
      quantitative polymerase chain reaction analysis of corresponding gene expression
      of proteins of interest was performed. RESULTS: Proteins differentially expressed
      in patent versus fused sutures included collagen 6A1 (Col6A1), fibromodulin,
      periostin, aggrecan, adipocyte enhancer-binding protein 1, and osteomodulin
      (OMD). Maximum likelihood-based G-test suggested that Col6A1, fibromodulin, and
      adipocyte enhancer-binding protein 1 are highly expressed in patent sutures
      compared with fused sutures, whereas OMD is up-regulated in fused sutures
      compared with patent sutures. These results were corroborated by
      immunohistochemistry. Quantitative polymerase chain reaction data point to an
      inverse relationship in proteins of interest to RNA transcript levels, in
      prematurely fused and patent sutures that potentially describes a feedback loop
      mechanism. CONCLUSIONS: Proteome analysis validated by immunohistochemistry may
      provide insight into the mechanism of cranial suture patency and disease from an
      osteoclast perspective. The authors results suggest a role of inflammatory
      mediators in nonsyndromic craniosynostosis. Col6A1 may aid in the regulation of
      suture patency, and OMD may be involved in premature fusion. Additional
      validation studies are required.

PMID- 29369996
TI  - Discussion: Whole-Proteome Analysis of Human Craniosynostotic Tissue Suggests a
      Link between Inflammatory Signaling and Osteoclast Activation in Human Cranial
      Suture Patency.

PMID- 29369997
TI  - Anatomical Uniqueness of Ear Morphology: A Novel Metrical Approach through Three
      Dimensional Superimposition.
AB  - Uniqueness of ear morphology has been a widely debated issue in cephaloscopy, but
      past studies used only two-dimensional approaches. In the current investigation,
      the right and left ears of 10 healthy adults were imaged twice by
      stereophotogrammetry at the interval of a few seconds. The ear images obtained
      from the two acquisitions were superimposed both within subject (group of
      matches) and among subjects (group of mismatches). A point-to-point root mean
      square distance was calculated between the two three-dimensional models.
      Differences according to side and group were assessed by two-way analysis of
      variance. In total, 200 superimpositions were performed. On average, the point-to
      point root mean square distance was 0.31 mm in cases of matches and 1.43 mm in
      cases of mismatches: differences were statistically significant (p < 0.01).
      Results provided quantitative data for the assessment of uniqueness of ear
      morphology, highlighting differences based on their three-dimensional morphology.

PMID- 29369998
TI  - Discussion: Percutaneous Mesh Expansion: A Regenerative Wound Closure
      Alternative.

PMID- 29369999
TI  - Paradoxical Frontalis Activation: An Underrecognized Consequence of Facial Palsy.
AB  - BACKGROUND: Aberrant reinnervation and synkinesis are common and debilitating
      after facial palsy. Paradoxical frontalis activation can antagonize eye closure
      and increase the risk of corneal damage. If recognized, judicious botulinum toxin
      injection to the affected side may reduce this risk. METHODS: One hundred
      consecutive patients with synkinesis were identified from a prospective database.
      Routine facial view photographs were converted to a standardized scale using iris
      diameter. The vertical distance from the midpoint of the midcanthal line to the
      inferior border of the eyebrow was measured bilaterally. A value of p < 0.05 was
      considered significant. RESULTS: Eighty-two patients were included, with a median
      age of 44 years (interquartile range, 33 to 59 years); 59 of the patients were
      women. The commonest cause was idiopathic (n = 55). The median time since onset
      of palsy was 13 months (interquartile range, 6.5 to 27 months). There was less
      midpoint of the midcanthal line to the inferior border of the eyebrow excursion
      on the synkinetic side of the face (p < 0.001). Twenty-two patients (27 percent)
      displayed paradoxical frontalis movement on the affected side of their face, with
      increased midpoint of the midcanthal line to the inferior border of the eyebrow
      distance (eyebrow raise) when attempting eye closure compared with eyebrow raise
      (n = 19), and tight eye closure compared with gentle eye closure (n = 3).
      CONCLUSIONS: This study highlights the phenomenon of paradoxical frontalis
      activation during eye closure. This is often underrecognized and may contribute
      to lagophthalmos. The authors found it to be present in 27 percent of patients
      with moderate or severe synkinesis. Further dynamic studies are required to
      understand the relationship among frontalis activity, eye closure, and the
      effects of its inhibition.

PMID- 29370000
TI  - Polyethylene Ear Reconstruction: A State-of-the-Art Surgical Journey.
AB  - BACKGROUND: The use of a porous high-density polyethylene implant for ear
      reconstruction is gradually gaining acceptance because it allows for a pleasing
      ear reconstruction in young children before they enter school. In response to
      this growing interest, the authors decided to write an article clarifying in
      detail all the steps of this challenging procedure. In this article, the authors
      also answer all the common questions that surgeons have when they come to observe
      the operation, or when they go back to their respective practices and start
      performing this procedure. METHODS: The authors describe in detail the operative
      steps that allow for a successful ear reconstruction using porous high-density
      polyethylene. The key parts of this operation are to meticulously harvest a well
      vascularized superficial temporoparietal fascia flap and to use appropriate color
      matched skin grafts. RESULTS: This method allows for a pleasing ear
      reconstruction with excellent definition, projection, symmetry, and long-term
      viability. CONCLUSION: The use of porous high-density polyethylene with a thin
      superficial temporoparietal fascia flap coverage is the authors' preferred method
      of ear reconstruction because it can be performed at an earlier age, in a single
      stage, as an outpatient procedure, and with minimal discomfort and psychological
      trauma for the patients and parents.

PMID- 29370001
TI  - Discussion: Polyethylene Ear Reconstruction: A State-of-the-Art Surgical Journey.

PMID- 29370002
TI  - Discussion: Redefining the Rectus Sheath: Implications for Abdominal Wall Repair.

PMID- 29370003
TI  - Electronic Communication in Plastic Surgery: Guiding Principles from the American
      Society of Plastic Surgeons Health Policy Committee.
AB  - BACKGROUND: With the advancement of technology, electronic communication has
      become an important mode of communication within plastic and reconstructive
      surgery. This can take the form of e-mail, text messaging, video conferencing,
      and social media, among others. There are currently no defined American Society
      of Plastic Surgeons guidelines for appropriate professional use of these
      technologies. METHODS: A search was performed on PubMed and the Cochrane
      database; terms included "telemedicine," "text messaging," "HIPAA," "metadata,"
      "video conferencing," "photo sharing," "social media," "Facebook," "Twitter," and
      "Instagram." Initial screening of all identified articles was performed; the
      level of evidence, limitations, and recommendations were evaluated and articles
      were reviewed. RESULTS: A total of 654 articles were identified in the level I
      screening process; after more comprehensive review, 41 articles fit inclusion
      criteria: social networking, 12; telemedicine, 11; text messaging, 10; metadata,
      four; video conferencing, three; and Health Insurance Portability and
      Accountability Act, one. General themes were identified from these articles and
      guidelines proposed. CONCLUSION: Electronic communication can provide an
      efficient method of information exchange for professional purposes within plastic
      surgery but should be used thoughtfully and with all professional, legal, and
      ethical considerations.

PMID- 29370004
TI  - Plastic Surgeon-Led Ultrasound.
AB  - BACKGROUND: Portable high-frequency ultrasound is a useful adjunct to a plastic
      surgeon's practice. With a short learning curve, this patient-friendly imaging
      modality has a variety of uses that aid patient management/treatment plans. The
      authors describe clinical cases and review the literature regarding ultrasound
      performed by the surgeon. METHODS: The Sonosite S-Nerve machine with the L25X
      transducer was used (depth, 4.3 cm). Clinical cases that ordinarily would have
      been referred to the radiology department were taken from the day-to-day practice
      of the senior author (M.G.). The clinical scenarios ranged from acute
      presentations to planned elective settings. RESULTS: Ultrasound was a useful
      adjunct in a variety of applications, ranging from acute hand trauma visualizing
      neurovascular bundles and tendons, to elements of reconstructive breast surgery
      such as fat grafting over an implant and scar release. The ultrasound machine was
      also used for determination of the depth and size of collections such as seromas
      to facilitate drainage, for identification of lymph nodes before transfer, and
      for acute presentations of conditions ranging from undiagnosed swelling to
      foreign body localization. CONCLUSIONS: The portable ultrasound machine has
      become an invaluable tool in the senior author's practice. In a short time and
      with a short learning curve, the authors' unit identified numerous applications
      for its use. From a patient perspective, it is noninvasive/nonpainful and has no
      deleterious radiation effects, and treatment plans can be enacted without delay.
      It is highly recommended that surgeons become familiar with this imaging modality
      and assimilate it into their daily practice. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, V.

PMID- 29370005
TI  - Fat Grafting: A Growing Problem?

PMID- 29370006
TI  - Direct-to-Implant versus Two-Stage Tissue Expander/Implant Reconstruction: 2-Year
      Risks and Patient-Reported Outcomes from a Prospective, Multicenter Study:
      Correction.

PMID- 29370007
TI  - Reply: The Evolution of Photography and Three-Dimensional Imaging in Plastic
      Surgery.

PMID- 29370008
TI  - Initiating Nutritional Support Before 72 Hours Is Associated With Favorable
      Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of
      a Randomized, Controlled Trial of Therapeutic Hypothermia.
AB  - OBJECTIVES: To understand the relationship between the timing of initiation of
      nutritional support in children with severe traumatic brain injury and outcomes.
      DESIGN: Secondary analysis of a randomized, controlled trial of therapeutic
      hypothermia (Pediatric Traumatic Brain Injury Consortium: Hypothermia, also known
      as "the Cool Kids Trial" (NCT 00222742). SETTINGS: Fifteen clinical sites in the
      United States, Australia, and New Zealand. SUBJECTS: Inclusion criteria included
      1) age less than 18 years, 2) postresuscitation Glasgow Coma Scale less than or
      equal to 8, 3) Glasgow Coma Scale motor score less than 6, and 4) available to be
      randomized within 6 hours after injury. Exclusion criteria included normal head
      CT, Glasgow Coma Scale equals to 3, hypotension for greater than 10 minutes (<
      fifth percentile for age), uncorrectable coagulopathy, hypoxia (arterial oxygen
      saturation < 90% for > 30 min), pregnancy, penetrating injury, and unavailability
      of a parent or guardian to consent at centers without emergency waiver of
      consent. INTERVENTIONS: Therapeutic hypothermia (32-33 degrees C for 48 hr)
      followed by slow rewarming for the primary study. For this analysis, the only
      intervention was the extraction of data regarding nutritional support from the
      existing database. MEASUREMENTS AND MAIN RESULTS: Timing of initiation of
      nutritional support was determined and patients stratified into four groups
      (group 1-no nutritional support over first 7 d; group 2-nutritional support
      initiated < 48 hr after injury; group 3-nutritional support initiated 48 to < 72
      hr after injury; group 4-nutritional support initiated 72-168 hr after injury).
      Outcomes were also stratified (mortality and Glasgow Outcomes Scale-Extended for
      Pediatrics; 1-4, 5-7, 8) at 6 and 12 months. Mixed-effects models were performed
      to define the relationship between nutrition and outcome. Children (n = 90, 77
      randomized, 13 run-in) were enrolled (mean Glasgow Coma Scale = 5.8); the
      mortality rate was 13.3%. 57.8% of subjects received hypothermia Initiation of
      nutrition before 72 hours was associated with survival (p = 0.01), favorable 6
      months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.03), and favorable
      12 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.04).
      Specifically, groups 2 and 3 had favorable outcomes versus group 1. CONCLUSIONS:
      Initiation of nutritional support before 72 hours after traumatic brain injury
      was associated with decreased mortality and favorable outcome in this secondary
      analysis. Although this provides a rationale to initiate nutritional support
      early after traumatic brain injury, definitive studies that control for important
      covariates (severity of injury, clinical site, calories delivered,
      parenteral/enteral routes, and other factors) are needed to provide definitive
      evidence on the optimization of the timing of nutritional support after severe
      traumatic brain injury in children.

PMID- 29370009
TI  - High-Volume Hydraulic Fracturing and Human Health Outcomes: A Scoping Review.
AB  - OBJECTIVE: Examine extent of peer-reviewed literature exploring human health
      effects of hydraulic fracturing (HVHF). METHODS: A scoping review methodology was
      used to examine peer-reviewed studies published from 2000 through 2017 that
      empirically examine direct health impacts of hydraulic fracturing. RESULTS:
      Through September 2017, only 18 studies were found published in peer-reviewed
      journals that met our requirements for inclusion in the review. Most of these
      studies resulted in positive or mixed findings of health outcomes. CONCLUSIONS:
      The paucity of studies reflects the difficulty in drawing direct connections
      between HVHF and human health outcomes. Many health outcomes may take years to
      emerge, exposure often occurs in lightly populated rural areas with older,
      poorer, and sicker residents, and diagnosis is difficult without physician
      knowledge of prior exposure. Primary care providers should record thorough
      histories to help guide future treatment.

PMID- 29370010
TI  - Return on Investment for a Payer-Provider Partnership to Improve Care Management
      of Employees and Early Retirees.
AB  - OBJECTIVE: A large employer partnered with local health care providers to pilot
      test an intensive nurse care manager program for employees and retirees. We
      evaluated its impact on health care utilization and costs. METHODS: A database
      was developed containing 2011 to 2015 health care enrollment and claims data for
      2914 patients linked to their nurse care manager data. We used a difference-in
      difference design to compare health care costs and utilization of members
      recruited for the pilot program and a propensity-score-matched comparison group.
      RESULTS: We found statistically significant reductions in doctors' office visits
      and prescription drug costs. A return-on-investment analysis determined that the
      program saved $0.83 for every dollar spent over the 2-year pilot study period.
      CONCLUSIONS: Employer-driven care management programs can succeed at reducing
      utilization, although they may not achieve cost neutrality in the short run.

PMID- 29370011
TI  - Health Status of Gulf War and Era Veterans Serving in the US Military in 2000.
AB  - OBJECTIVE: This research describes Gulf War and era veterans enrolled in the
      Millennium Cohort Study, who were sampled from US military personnel serving in
      2000, and compares health characteristics of this sample to a Department of
      Veterans Affairs study sampled from the complete population. METHODS:
      Demographics characteristics of this sample were described. Self-reported health
      characteristics were compared between the two studies. RESULTS: Gulf War and era
      veterans in the Millennium Cohort were generally healthier than in the VA study;
      they had fewer medical conditions and mental health disorders and better self
      reported health. In both studies, Gulf War veterans had poorer health outcomes
      than era veterans. CONCLUSION: The Millennium Cohort Study is a unique resource
      for examining the long-term health effects of Gulf War deployment, particularly
      comparing deployed and nondeployed personnel and examining illnesses with long
      latencies.

PMID- 29370012
TI  - In Memoriam - James M. Melius, MD, DrPH.

PMID- 29370013
TI  - Differences in Work-Related Adverse Events by Sex and Industry in Cases Involving
      Compensation for Mental Disorders and Suicide in Japan From 2010 to 2014.
AB  - OBJECTIVE: This study aimed to clarify whether work-related adverse events in
      cases involving compensation for mental disorders and suicide differ by sex and
      industry using a database containing all relevant cases reported from 2010 to
      2014 in Japan. METHODS: A total of 1362 eligible cases involving compensation for
      mental disorders (422 females and 940 males) were analyzed. RESULTS: Among males,
      55.7% of cases were attributed to "long working hours." In both sexes, the
      frequencies of cases attributed to "long working hours" and other events differed
      significantly by industry. Among cases involving compensation for suicide, 71.4%
      were attributed to "long working hours." CONCLUSIONS: The frequency distribution
      of work-related adverse events differed significantly by sex and industry. These
      differences should be taken into consideration in the development of industry
      specific preventive measures for occupational mental disorders.

PMID- 29370014
TI  - Resilience Training for Work-Related Stress Among Health Care Workers: Results of
      a Randomized Clinical Trial Comparing In-Person and Smartphone-Delivered
      Interventions.
AB  - OBJECTIVE: The aim of this study was to assess whether an in-person mindfulness
      based resilience training (MBRT) program or a smartphone-delivered resiliency
      based intervention improved stress, well-being, and burnout in employees at a
      major tertiary health care institution. METHODS: Sixty participants were
      randomized to a 6-week MBRT, a resiliency-based smartphone intervention, or an
      active control group. Stress, well-being, and burnout were assessed at baseline,
      at program completion, and 3 months postintervention. RESULTS: Both the MBRT and
      the smartphone groups showed improvements in well-being, whereas only the MBRT
      group showed improvements in stress and emotional burnout over time. The control
      group did not demonstrate sustained improvement on any outcome. CONCLUSION:
      Findings suggest that brief, targeted interventions improve psychological
      outcomes and point to the need for larger scale studies comparing the individual
      and combined treatments that can inform development of tailored, effective, and
      low-cost programs for health care workers.

PMID- 29370015
TI  - Effort-Reward Imbalance, Work-Privacy Conflict, and Burnout Among Hospital
      Employees.
AB  - OBJECTIVE: Studies investigating the relative importance of effort-reward
      imbalance and work-privacy conflict for burnout risk between professional groups
      in the health care sector are rare and analyses by educational attainment within
      professional groups are lacking. METHODS: The study population consists of 1422
      hospital employees in Switzerland. Multivariate linear regression analyses with
      standardized coefficients were performed for the overall study population and
      stratified for professional groups refined for educational attainment. RESULTS:
      Work-privacy conflict is a strong predictor for burnout and more strongly
      associated with burnout than effort-reward imbalance in the overall study
      population and across all professional groups. Effort-reward imbalance only had a
      minor effect on burnout in tertiary-educated medical professionals. CONCLUSION:
      Interventions aiming at increasing the compatibility of work and private life may
      substantially help to decrease burnout risk of professionals working in a health
      care setting.

PMID- 29370016
TI  - Risk Factors for Declines in Kidney Function in Sugarcane Workers in Guatemala.
AB  - OBJECTIVES: To characterize kidney function of sugarcane workers in Guatemala
      over the 6-month harvest and identify risk factors associated with changes in
      kidney function. METHODS: Demographic and biological data were collected for 330
      sugarcane cutters at the beginning and end of the harvest. Multivariable
      regression analyses were used to assess factors related to kidney function.
      RESULTS: A decline in kidney function across the harvest was observed in 36% of
      the participants. Risk factors associated with this decline included working at a
      particular plantation mill, local area workers compared with highland workers,
      and current smokers. CONCLUSION: Results showed both occupational and behavioral
      factors play significant roles in declines in kidney function. These results
      underline the need for a comprehensive approach to the epidemic as well as
      further investigation of risk factors to guide research and interventions.

PMID- 29370017
TI  - MTHFR Gene Polymorphism Is Associated With DNA Hypomethylation and Genetic Damage
      Among Benzene-Exposed Workers in Southeast China.
AB  - OBJECTIVE AND METHODS: To analyze the association between global DNA methylation
      and single-nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase
      (MTHFR). MTHFR polymorphisms rs1801133 and rs1801131 were detected using the
      restriction fragment length polymorphism method, and cytokinesis-block
      micronucleus (MN) frequency and global DNA methylation was measured in workers
      from 410 shoe factories. RESULTS: A multilinear regression analysis demonstrated
      that DNA methylation of the TT variant allele of rs1801133 was lower than that of
      the CC wild type allele (Exp(beta) [95% CI], 0.76 [0.56, 1.02], P = 0.071), with
      a P-value approaching significance. A significantly increased MN frequency was
      observed for carriers of the TT genotype (frequency ratio = 1.27, 95% CI: 1.07
      1.51, P < 0.01). CONCLUSION: The results imply that the TT genotype in rs1801133
      is associated with global DNA hypomethylation, which may influence the induction
      of MN following exposure to benzene.

PMID- 29370018
TI  - Differentiating Occult Branch Retinal Artery Occlusion from Primary Open-angle
      Glaucoma.
AB  - SIGNIFICANCE: Clinical findings in occult branch retinal artery occlusion (BRAO)
      can mimic those of primary open-angle glaucoma (POAG). Because management of
      these conditions substantially differs, accurate diagnosis is crucial. Our
      comparative analysis indicates that specific macular thickness variables reliably
      differentiate these conditions and that macular scanning may enhance routine
      glaucoma evaluation. PURPOSE: The aim of this study was to identify clinical
      factors that reliably and efficiently identify occult BRAO masquerading as POAG.
      METHODS: All subjects had comprehensive eye examinations including measurements
      of retinal nerve fiber layer and macular thickness (MT) using spectral-domain
      optical coherence tomography (SD-OCT). All subjects were asymptomatic for
      previous acute vision loss episodes, had optic nerve appearances suggestive of
      glaucoma, and exhibited SD-OCT retinal nerve fiber layer thinning with
      corresponding visual field loss. Macular thickness scans were divided into 64
      individual thickness blocks with thin MT blocks defined by the lower 99%
      confidence interval from a group of normal eyes. We defined BRAO by the presence
      of regional inner retinal thinning with lack of inner-layer stratification on
      macular SD-OCT b-scan images that spatially corresponded with arteriolar
      distribution and visual field loss location. Primary open-angle glaucoma eyes
      were selected to match the BRAO eyes by age and disease severity. Pairwise and
      receiver operating characteristic curve analyses were used to compare occult BRAO
      and POAG eyes. RESULTS: Compared with POAG (n = 52), occult BRAO eyes (n = 11)
      demonstrated lower cup-disc ratio, greater intereye and intraeye (superior vs.
      inferior) MT asymmetry, and higher frequency of thin MT blocks (<200 MUm). Area
      under the receiver operating characteristic curve (AUC) for differentiating these
      conditions was highest for intraeye MT asymmetry (AUC = 0.990 [95% confidence
      interval, 0.925 to 1.000]) and number of thin MT blocks (AUC = 0.993 [95%
      confidence interval, 0.929 to 1.000]). CONCLUSIONS: Macular thickness parameters
      provided accurate and efficient diagnostic capability in this study. Considering
      the clinical implications of inaccurate diagnosis, macular scanning may be
      important in baseline glaucoma evaluation.

PMID- 29370019
TI  - Can Corneal Biomechanical Properties Explain Difference in Tonometric Measurement
      in Normal Eyes?
AB  - SIGNIFICANCE: Corneal biomechanical parameters can affect intraocular pressure
      (IOP) measurements by different tonometers compared with Goldmann applanation
      tonometer. This study implies that corneal hysteresis (CH) and corneal resistance
      factor (CRF) better explain variability in IOP measurements. PURPOSE: The aim of
      this study was to evaluate the effect of corneal properties on the difference in
      IOP measured by the Ocular Response Analyzer (ORA), Rebound Tonometer (RBT),
      Dynamic Contour Tonometer (DCT), and Tono-Pen from the Goldmann applanation
      tonometer (GAT). METHODS: An observational study was done on healthy participants
      in a tertiary eye care center. Corneal curvature was measured with a manual
      keratometer prior to IOP measurements. Intraocular pressure was measured by a
      single trained examiner with ORA, RBT, DCT, GAT, and Tono-Pen. CH and CRF were
      measured using the ORA. Central corneal thickness was measured using the
      ultrasonic pachymeter. Only the right eye was included for analysis. One-way
      analysis of variance was performed to compare variables, Bland-Altman plots to
      assess agreement, and regression analyses to study associated factors. RESULTS:
      We included 82 eyes of 82 participants with a mean age of 40.9 (14.3) years. Mean
      +/- SD DCT IOP (15.22 +/- 1.98) mmHg was significantly higher than GAT IOP (13.73
      +/- 2.42) (P = .01) and ORA Goldmann correlated IOP (13.66 +/- 3.16) (P = .003).
      The limits of agreement between GAT and other tonometers measurements ranged
      between -5.0 and 2.1 mmHg. With multiple linear regression analyses, CH and CRF
      were found to be associated with the measured IOP differences between GAT and ORA
      (corneal compensated IOP and Goldmann correlated IOP) (P < .001) and DCT (P =
      .014, <.001) whereas differences between GAT and RBT measurements were
      independently explained by corneal curvature (P = .035) and central corneal
      thickness (P = .045). CONCLUSIONS: There was good agreement between GAT and other
      tonometers, but was not good enough for them to be used interchangeably. A
      combination of CH and CRF may better explain the variability between GAT and
      tonometers.

PMID- 29370020
TI  - Comparison of Scleral Tono-Pen Intraocular Pressure Measurements with Goldmann
      Applanation Tonometry.
AB  - SIGNIFICANCE: Measuring the intraocular pressure (IOP) on the sclera can be an
      alternative to conventional corneal measurement in eyes with scarred corneas.
      However, these measurements have to be evaluated prior in normal eyes. Our study
      aimed to evaluate scleral IOP using Tono-Pen and compared it with corneal
      Goldmann applanation measurements. PURPOSE: The aim of this study was to evaluate
      the ability of limbal and scleral Tono-Pen IOP readings to predict central
      corneal Goldmann applanation tonometry (GAT) readings in eyes with normal
      corneas. METHODS: In a cross-sectional study, 115 eyes of 115 patients attending
      a tertiary eye care center underwent GAT on the central cornea followed by Tono
      Pen readings at the central cornea, at the limbus, and at the sclera. Bland
      Altman plots were used to determine the agreement between different methods of
      IOP measurement. RESULTS: The median IOP (interquartile range) by GAT performed
      on the central cornea was 18 (16, 24) mmHg, and the IOP ranged from 10 to 54
      mmHg. The median IOPs (interquartile range) by Tono-Pen obtained at central
      cornea, limbus, and sclera were 16 (13, 23), 23 (17, 28), and 33 (27, 44) mmHg,
      respectively. The Pearson correlation coefficient and the 95% limits of agreement
      between GAT readings and Tono-Pen readings at the central cornea were 0.9 (P <
      .001) and -4.9 to 8.74 mmHg, respectively. The correlation coefficient between
      GAT readings and Tono-Pen readings at the limbus and GAT readings and Tono-Pen
      readings at the sclera was 0.46 (P < .001) and 0.23 (P = .01), respectively. The
      95% limits of agreement between these pairs of readings were -20.55 to 13.66 and 
      44.02 to 13.37 mmHg, respectively. CONCLUSIONS: This study showed limited ability
      of Tono-Pen readings obtained at the limbus and sclera to predict the central
      corneal GAT IOP readings in eyes with normal corneas at various IOP ranges.

PMID- 29370021
TI  - The Role of Minimally Invasive Glaucoma Surgery Devices in the Management of
      Glaucoma.
AB  - SIGNIFICANCE: Noncompliance is a problem affecting glaucoma patients. Approaches
      to improve adherence include the use of drug-delivery systems and safer forms of
      surgery. Minimally invasive glaucoma surgery (MIGS) has reduced complications,
      particularly in combination with cataract surgery, and with its good intraocular
      pressure (IOP) reduction may reduce or eliminate glaucoma medications.Glaucoma is
      a progressive disease and a leading cause of irreversible blindness. Elevated IOP
      is the most important risk factor, but effective medical management is dependent
      on patient adherence. This review summarizes the adherence problem in glaucoma
      and the efforts, including MIGS, to provide effective IOP control that is not
      dependent on patient compliance.The current understanding of patient adherence to
      pharmacological treatment of glaucoma is discussed including the challenges
      facing glaucoma patients. Historical approaches to providing IOP control in a
      sustained and reliable way are presented culminating in a review of the
      burgeoning use of MIGS devices.It is estimated that, in the United States, 27% of
      prescriptions written, across all medications, are not filled or are filled but
      not taken. For ocular hypotensive medications, even when filled, a large
      percentage (which varies widely by study) are not instilled as prescribed. To
      address this problem, methods for sustained drug delivery have been and continue
      to be developed, as well as surgical and laser approaches. Most recently, MIGS
      devices have gained popularity because of the ease of implantation during
      cataract surgery, favorable safety profile, and the possibility for effective and
      long-lasting IOP lowering, as well as the reduction or elimination of need for
      IOP-lowering medication.Poor adherence to treatment is relatively common among
      glaucoma patients and is associated with progression of disease. Recommending
      MIGS implantation during cataract surgery may offer optometrists a valuable
      treatment option in managing glaucoma patients, particularly where good adherence
      is in doubt.

PMID- 29370023
TI  - Intraocular Pressure Response to Maximal Exercise Test during Recovery.
AB  - SIGNIFICANCE: The main aim of this study was to determine the intraocular
      pressure (IOP) response to maximal incremental running test during 30 minutes of
      recovery. Exhaustive exercise induced a highly individually variable IOP
      response, which was related to its initial value and the initial heart rate.
      PURPOSE: The purpose of the study was to analyzed the IOP response to a maximal
      incremental running test in healthy women during a 30-minute recovery period.
      Secondarily, the study attempted to determine if the IOP was dependent on its
      baseline, maximal oxygen uptake, initial heart rate, and autonomic nervous system
      regulation. METHODS: Twenty-four healthy women between the ages of 19 and 30
      years were recruited for the study. Initial IOP (baseline), heart rate, and
      autonomic nervous system regulation were measured after 30 minutes of rest. Each
      subject then underwent an incremental running test on a treadmill to reach the
      maximal physical activity and to determine physical fitness based on maximal
      oxygen uptake. Intraocular pressure and autonomic nervous system activity were
      measured immediately after completion of the physical activity during a 30-minute
      recovery period in the supine position. RESULTS: The IOP variability increased
      markedly after the exercise up to 1.7-fold of the resting state. The IOP before
      and after exercise did not differ significantly; however, the lower baseline
      revealed a significant increase in comparison with the higher baseline. The time
      course of the IOP changes was significantly influenced by the initial heart rate.
      All other effects, interactions, and correlations were insignificant.
      CONCLUSIONS: The IOP response after maximal exercise was highly dependent on the
      individual. The IOP seems to be slightly increasing with a significant dependence
      on its resting baseline and initial heart rate.

PMID- 29370022
TI  - Diurnal Intraocular Pressure Fluctuations with Self-tonometry in Glaucoma
      Patients and Suspects: A Clinical Trial.
AB  - SIGNIFICANCE: This article shows that self-tonometry can provide robust measures
      of diurnal intraocular pressure (IOP) and also detect changes to IOP in response
      to treatment within a short period of monitoring. These advances in IOP
      monitoring may contribute to improved management of glaucoma patients and
      suspects. PURPOSE: The aim of this study was to prospectively investigate the
      utility of rebound self-tonometry performed over several weeks for detecting
      diurnal IOP fluctuations in glaucoma patients and suspects and also initial
      response to topical treatment in glaucoma patients. METHODS: Forty patients were
      recruited following glaucoma-specific examination. Subsequent to successful
      training with the iCare HOME tonometer, patients were instructed to measure IOP,
      in a sitting position, four times a day over 4 to 6 weeks. Date, time,
      laterality, and IOP downloaded from the tonometer and clinical examination data,
      including applanation IOP and corneal thickness, were analyzed. A user
      satisfaction survey was also administered at study completion. t Test and
      analysis of variance were used to compare groups and IOP across days. Pearson
      correlation was used to compare measurements to Goldmann applanation tonometry
      and IOP measurements from the first day/s to the overall mean IOP. RESULTS:
      Twenty-seven patients (18 suspects and 9 glaucoma patients) completed data
      collection. Patients self-measured IOP on 118 (+/-29) occasions for 40 (+/-7.4)
      days. Two dominant patterns of fluctuation were revealed: peak IOP upon awakening
      (n = 11) and at midday (n = 13). Diurnal IOP measured in the first 7 days showed
      strong correlation to diurnal IOP across the entire study period (r = 0.82, P <
      .0001). Within 24 hours of treatment commencement (latanoprost 0.005% ophthalmic
      solution), IOP reduced from 23.9 (+/-5.2) to 16.1 (+/-2.6) mmHg. Overall,
      patients rated the instrument as easy to use, although difficulties with correct
      alignment were expressed. CONCLUSIONS: Rebound self-tonometry demonstrated
      utility for measuring diurnal IOP fluctuations in most patients, hence enhancing
      management of patient with or at risk of developing glaucoma.

PMID- 29370024
TI  - Assessing the True Intraocular Pressure in the Non-human Primate.
AB  - SIGNIFICANCE: For glaucoma patients, high intraocular pressure (IOP) is a risk
      factor for progressive neuropathy. Similarly, animal models used to study the
      disease are based on an experimental elevation of IOP. Thus, accurate IOP
      measurements are important in characterizing experimental models and resulting
      effects. PURPOSE: The purpose of the present study was to investigate IOP
      measurements in a non-human primate model of experimental glaucoma by comparing
      clinical tonometry (Tono-Pen and TonoVet) to the true IOP from intracameral
      manometry. METHODS: A total of 17 rhesus macaque eyes from 12 animals were used
      for this study. Eleven eyes had no previous experimental intervention, whereas
      six eyes were at varying stages of laser-induced experimental glaucoma. IOPs were
      adjusted by inserting a needle in the anterior chamber that was attached to a
      pressure transducer and syringe pump system. The anterior chamber IOP was
      adjusted to values between 10 and 50 mmHg and corresponding measures with Tono
      Pen and TonoVet were taken. RESULTS: The IOPs by TonoVet and Tono-Pen were
      linearly related over the range of pressures tested (slope = 0.68 normal/healthy
      and 0.72 experimental glaucoma). For the most, TonoVet measures overestimated IOP
      at all anterior chamber pressure settings (mean difference of 3.17 mmHg, 95% CI
      12.53 to -4.74 normal and 3.90 mmHg, 95% CI 12.90 to -6.53 experimental
      glaucoma). In contrast, Tono-Pen measures overestimated IOP at lower IOPs and
      underestimated at higher IOP (slope = -0.26 normal and -0.21 experimental
      glaucoma). CONCLUSIONS: The TonoVet and Tono-Pen tonometers that are often used
      to assess IOP in both clinical and experimental settings generally reflect the
      status of IOP, but the results from this study suggest that the instruments need
      calibration with true anterior chamber pressure for accurate measures in
      experimental models of glaucoma.

PMID- 29370026
TI  - Results for Water-drinking Test, before and after Laser Iridotomy, in Primary
      Angle-closure Suspects.
AB  - SIGNIFICANCE: Intraocular pressure and ocular biometric changes were similar
      before and after laser iridotomy in response to the water-drinking test in a
      cohort of patients at risk of angle closure. The water-drinking test does not
      seem to be a good provocative test to determine which eyes would benefit from a
      laser iridotomy. Our data call into question the preoperative predictive value of
      this test. PURPOSE: The aim of this study was to evaluate the effect of water
      drinking test on intraocular pressure and ocular biometric parameters, before and
      after laser peripheral iridotomy, in patients with an occludable angle. METHODS:
      Twenty-seven patients, who met the inclusion criteria and had at least 180
      degrees of iridotrabecular apposition, underwent a complete eye examination
      followed by the measurement of ocular biometric (using LenStar LS-900; Haag
      Streit AG, Koeniz, Switzerland) and anterior chamber parameters (using Pentacam
      HR; Oculus Optikgerate GmbH, Wetzlar, Germany). All the measurements were
      repeated 30 minutes after the water-drinking test. Two weeks after laser
      peripheral iridotomy, all the measurements were repeated both before and after
      the water-drinking test. RESULTS: The mean +/- SD of the age of the participants
      was 57 +/- 9 years, and 23 (85.2%) were male. Intraocular pressure increased
      after the water-drinking test in both pre-laser peripheral iridotomy (17.0 vs.
      19.3 mmHg, P < .001) and post-laser peripheral iridotomy (15.6 vs. 18.6 mmHg, P <
      .001) conditions. The thickness values of central cornea increased slightly after
      the water-drinking test in pre-laser peripheral iridotomy (535 vs. 538 MUm, P =
      .001) compared with post-laser peripheral iridotomy (532 vs. 536 MUm, P = .003).
      The water-drinking test had no significant effect on other biometric or anterior
      chamber parameters, before or after laser peripheral iridotomy. CONCLUSIONS: The
      water-drinking test increased intraocular pressure, both before and after laser
      peripheral iridotomy. Laser peripheral iridotomy had no significant effect on the
      amount of intraocular pressure change after the water-drinking test. The water
      drinking test has no effect on other biometric or anterior chamber parameters.

PMID- 29370025
TI  - Identifying Glaucomatous Damage to the Macula.
AB  - SIGNIFICANCE: Measurements of the macula have been increasingly used to diagnose
      and manage patients with glaucoma. Asymmetry analysis was clinically introduced
      to assess damage to the macular ganglion cells in patients with glaucoma, but its
      effectiveness is limited by high normal between-subject variability. PURPOSE: We
      aimed to reduce the high normal between-subject variability and improve the
      potential of asymmetry analysis to identify glaucomatous damage to the macula.
      METHODS: Twenty patients with glaucoma (aged 57 to 85 years) and 30 age-similar
      control subjects (aged 53 to 89 years) were recruited from a longitudinal
      glaucoma study. Participants were imaged with the Spectralis OCT using the
      posterior pole protocol; measurements of the averaged retinal thickness and
      ganglion cell layer (GCL) thickness were obtained. We established three zones per
      hemifield within the central +/-9 degrees , based on the lowest between-subject
      variability that we previously found and the course of retinal nerve fiber layer
      projections. The criteria for flagging abnormality were at least two contiguous
      zones when P < 5% or one zone when P < 1% with two-tailed tests. RESULTS: Between
      subject variability of the asymmetry analysis for both retinal and GCL
      thicknesses remained lower than that of the average thickness across each zone in
      control subjects (F > 2.52, P < .01). Asymmetry analysis of retinal and GCL
      thicknesses flagged 16 and 18 of 20 patients, respectively. CONCLUSIONS: Between
      subject variability was reduced in control subjects using the three zones; our
      criteria identified glaucomatous damage to the macula in most of the patients. We
      used high-density B-scans to confirm the patterns of the glaucomatous damage we
      found in this study.

PMID- 29370027
TI  - Muscular Strength Is Associated with Higher Intraocular Pressure in Physically
      Active Males.
AB  - SIGNIFICANCE: The positive association between intraocular pressure (IOP) and
      relative maximum force may have relevance for exercise recommendations when IOP
      is a concern. PURPOSE: The relationship between exercise and IOP has been
      approached in several studies. However, the influence of muscle function on IOP
      remains underexplored. This study aimed to determine the relationship between the
      maximal mechanical capabilities of muscles to generate force, velocity, and power
      with IOP. METHODS: Sixty-five physically active males participated in this cross
      sectional study. Baseline IOP measures were obtained by rebound tonometry, and
      participants performed an incremental loading test in the ballistic bench press.
      RESULTS: Baseline IOP showed a strong positive correlation with relative maximum
      force (r65 = 0.85, P < .001) relative maximum power (r65 = 0.85, P < .001), and
      relative one-repetition maximum (r65 = 0.91, P < .001). Also, a moderate positive
      association was obtained between baseline IOP and maximum force (r65 = 0.74, P <
      .001), maximum power (r65 = 0.72, P < .001), and maximum dynamic strength (r65 =
      0.80, P < .001). No significant correlations between IOP and maximal velocity
      were obtained (all P > .05). CONCLUSIONS: There is a positive association between
      greater upper-body power and strength with higher baseline IOP, which might have
      important implications in the management of ocular health and especially in
      individuals constantly involved in resistance training programs (e.g., military
      personnel, weightlifters). The possible protective effect of high fitness level
      on the acute IOP response to strength exercise needs to be addressed in future
      studies.

PMID- 29370028
TI  - THROMBOCYTOPENIA AS A RISK FACTOR FOR RETINOPATHY OF PREMATURITY.
AB  - PURPOSE: To study the association between thrombocytopenia and retinopathy of
      prematurity (ROP). METHODS: The case-control study was conducted on preterm
      newborns with ROP between January 2011 and January 2014, retrospectively. The
      patients were assigned into two groups: Cases required intervention and controls
      developed no or Stage I ROP. RESULTS: Eighty-one premature infants with Type I
      ROP were enrolled to the study with a mean gestational age of 27.6 +/- 2.1
      (range: 24-32) weeks and birth weight of 993 +/- 292 (range: 560-1,930) g. Mean
      follow-up time was 38.3 +/- 2.7 weeks (min: 32 and max: 46 weeks). Cases were
      individually matched to a set of controls (1:1 ratio). Thrombocytopenia
      (<150.000/mm) was seen in 58 (71.6%) of the cases with Type I ROP, whereas only
      17 (21%) of the controls had thrombocytopenia (P < 0.001). Logistic regression
      analysis showed that bronchopulmonary dysplasia and thrombocytopenia were
      significantly associated with Type I ROP (relative risk [95% confidence
      interval]: 4.19 [1.47-12] and 6.69 [2.83-15.9], respectively). The
      thrombocytopenia ratio (P = 0.073), thrombocytopenia 1 week before intervention
      (P = 0.076) and platelet transfusion ratio (P = 0.062) tended to be higher in
      Zone I ROP compared with Zone II ROP. CONCLUSION: In our study, there was a
      significant association between thrombocytopenia and Type I ROP.

PMID- 29370029
TI  - SUBRETINAL ENDOSCOPIC SURGERY TO TREAT LARGE SUBRETINAL HEMORRHAGES SECONDARY TO
      AGE-RELATED MACULAR DEGENERATION.
AB  - PURPOSE: To evaluate the potential of subretinal endoscopic surgery as a novel
      treatment for large subretinal hemorrhage secondary to age-related macular
      degeneration. METHODS: Five patients with large subretinal hemorrhage secondary
      to age-related macular degeneration underwent subretinal endoscopic surgery, with
      a minimum follow-up of 12 months. RESULTS: The large subretinal hemorrhage was
      completely removed by subretinal endoscopic surgery without a large retinotomy in
      all cases. The fibrovascular pigment epithelial detachment including choroidal
      neovascularization was completely removed in four cases. In three of these cases,
      the bleeding was confirmed to be originating from one point of rupture in the
      Bruch membrane, which was treated by coagulation using intraocular diathermy.
      Although visual acuity improved in three cases, it deteriorated and remained
      stable in one case each. Fibrovascular pigment epithelial detachment persisted in
      one patient after surgery; he needed anti-vascular endothelial growth factor
      therapy, whereas the other four did not because their fibrovascular pigment
      epithelial detachment was removed. At the final follow-up, no severe
      postoperative complications, such as retinal detachment or proliferative
      vitreoretinopathy, were noted. CONCLUSION: Subretinal endoscopic surgery can
      completely remove subretinal hemorrhage and fibrovascular pigment epithelial
      detachment including choroidal neovascularization without a large retinotomy. It
      also aids in the direct and detailed confirmation of subretinal lesions by
      ophthalmic endoscope.

PMID- 29370030
TI  - BETA-D-GLUCAN TESTING IN PATIENTS WITH FUNGAL ENDOPHTHALMITIS.
AB  - PURPOSE: To review the literature on beta-D-glucan (BDG) testing in fungal
      endophthalmitis. METHODS: Review of primary literature using PubMed through April
      2017 and presentation of an illustrative case report. A total of 231 articles
      were identified and 43 were ultimately chosen for review based on relevance and
      presence of ophthalmologic examination and objective data. RESULTS: Beta-D-glucan
      is a major component of fungal cell walls. It is quantified using a calorimetry
      based Fungitell assay based on modification of the limulus amebocyte lysate.
      Serum BDG levels are commonly used clinically in conjunction with other tests for
      early surveillance and diagnosis of invasive fungal infections. In the ophthalmic
      literature, elevated levels of BDG have been detected in vitreous fluid of
      patients undergoing vitrectomy for fungal endophthalmitis, tear fluid of patients
      with mycotic keratitis, and serum of a patient with bilateral endogenous
      subretinal abscesses. Elevated serum BDG levels appear to be highly associated
      with fungal endophthalmitis. Potential uses and considerations with regards to
      test limitations are discussed. CONCLUSION: Beta-D-glucan testing may be used as
      an adjunct to support a diagnosis, initiate pharmacologic therapy or surgical
      intervention, and optimize overall clinical management in patients diagnosed with
      or under clinical suspicion for invasive fungal infections, including
      endophthalmitis. Additional clinical studies are necessary to fully characterize
      the utility of BDG testing in patients with fungal endophthalmitis.

PMID- 29370032
TI  - Chorioretinal Punched-Out Lesions in Pseudoxanthoma Elasticum.

PMID- 29370031
TI  - COMPARISON OF VISUAL AND ANATOMICAL OUTCOMES OF EYES UNDERGOING TYPE I BOSTON
      KERATOPROSTHESIS WITH COMBINATION PARS PLANA VITRECTOMY WITH EYES WITHOUT
      COMBINATION VITRECTOMY.
AB  - PURPOSE: To determine whether 1-year visual and anatomical results after surgery
      combining pars plana vitrectomy, Boston keratoprosthesis, and a glaucoma drainage
      device as needed are similar, better, or worse than Boston keratoprosthesis
      initial implantation alone. METHODS: We performed a retrospective review of adult
      patients undergoing Boston keratoprosthesis at our institution. Visual acuity
      outcomes, anatomical results, and complication rates of patients undergoing
      combination surgery (including pars plana vitrectomy and a posterior glaucoma
      drainage device) were compared with those undergoing keratoprosthesis placement
      alone. RESULTS: There were 70 eyes in the keratoprosthesis alone group and 55
      eyes in the keratoprosthesis with pars plana vitrectomy group. Mean follow-up
      durations were 54.67 months in the keratoprosthesis alone group and 48.41 months
      in the combination group. Baseline mean Snellen equivalent visual acuities were
      worse for the combination group compared with the keratoprosthesis alone group (P
      = 0.027). Visual acuities improved postoperatively by 1 month after
      keratoprosthesis implantation for both groups and improved three or more lines of
      Snellen acuity in the majority of eyes for both groups (>=72% by 12 months). Eyes
      undergoing pars plana vitrectomy had lower rates of de novo (P = 0.015) and
      significantly lower rates of secondary procedures (P = 0.002) at 1 year. One year
      complications rates for retroprosthetic membrane formation, retinal detachment,
      hypotony, cystoid macular edema, epiretinal membrane formation, endophthalmitis,
      and corneal melting were similar for both groups. CONCLUSION: Compared with
      keratoprosthesis alone, combining keratoprosthesis with pars plana vitrectomy and
      a glaucoma drainage device as needed, resulted in lower rates of de novo
      glaucoma, lower rates of additional surgical procedures, similar visual acuity
      outcomes at 1 year, and did not result in higher complication rates.

PMID- 29370033
TI  - AUTOSOMAL DOMINANT VITREORETINOCHOROIDOPATHY: When Molecular Genetic Testing
      Helps Clinical Diagnosis.
AB  - PURPOSE: Autosomal dominant vitreoretinochoroidopathy is an extremely rare
      disease, which belongs to the BEST1-related disease spectrum. METHODS: Report of
      five patients with an initial diagnosis of atypical rod-cone dystrophy, for whom
      autosomal dominant vitreoretinochoroidopathy was retrospectively diagnosed on
      genetic results using targeted next-generation sequencing. Each patient had a
      comprehensive ophthalmic examination including multimodal retinal imaging and
      functional evaluation. RESULTS: Visual acuity ranged from <20/800 to 20/25. Two
      patients had narrowed angle with history of acute angle-closure glaucoma for one
      patient. Full-field electroretinogram showed severe reduction of both scotopic
      and photopic responses for 3/5 patients. Electrooculogram could be performed for
      one of the two patients with moderate alterations of full-field
      electroretinogram. It revealed severe light rise abnormalities with decreased
      Arden ratio (125% right eye, 145% left eye) in keeping with generalized severe
      dysfunction of the retinal pigment epithelium. On fundoscopy, the pathognomonic
      circumferential hyperpigmented band of the peripheral retina was totally absent
      in two patients. CONCLUSION: This report highlights the high phenotypic
      variability of autosomal dominant vitreoretinochoroidopathy, which may be
      misdiagnosed, especially in advanced forms with severe generalized photoreceptor
      dysfunction mimicking retinitis pigmentosa. Targeted next-generation sequencing
      can contribute to the proper clinical diagnosis, especially in case of atypical
      phenotypic features of autosomal dominant vitreoretinochoroidopathy.

PMID- 29370034
TI  - INCIDENCE OF ENDOPHTHALMITIS AFTER VITRECTOMY: A Systematic Review and Meta
      analysis.
AB  - PURPOSE: The purpose of this study was to review the literature reporting rates
      of postoperative endophthalmitis after pars plana vitrectomy and investigate
      whether modern microincision vitrectomy surgery (MIVS) increases the
      postoperative endophthalmitis rate, compared with traditional 20-gauge (20 G)
      vitrectomy. METHODS: A comprehensive literature search was performed to identify
      studies describing the incidence of post-pars plana vitrectomy endophthalmitis. A
      meta-analysis of comparative studies reporting the endophthalmitis rates after
      MIVS versus 20 G vitrectomy was also conducted. RESULTS: A total of 31 studies
      reported 199 endophthalmitis cases in 363,544 participants (0.05%). The incidence
      of endophthalmitis after 20 G vitrectomy was 0.04% (88/229,435), compared with
      0.03% (8/27,326) after 23 G and 0.11% (33/29,676) after 25 G. The meta-analysis
      demonstrated that the incidence of endophthalmitis was higher after MIVS (23 G/25
      G) compared with 20 G vitrectomy (odds ratio = 3.39, 95% confidence interval,
      1.39-8.23). In a subgroup analysis, we also found an increased risk of
      endophthalmitis after 25 G compared with 20 G vitrectomy (odds ratio = 4.09, 95%
      confidence interval, 2.33-7.18), but not for 23 G versus 20 G (odds ratio = 1.14,
      95% confidence interval, 0.47-2.78). CONCLUSION: The incidence of post-pars plana
      vitrectomy endophthalmitis was low, with no significant differences between 23 G
      MIVS and 20 G vitrectomy, but 25 G MIVS may result in a higher postoperative
      endophthalmitis rate.

PMID- 29370035
TI  - MACULAR ATROPHY INCIDENCE IN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR-TREATED
      NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Risk Factor Evaluation for
      Individualized Treatment Need of Ranibizumab or Aflibercept According to an
      Observe-and-Plan Regimen.
AB  - PURPOSE: To investigate factors associated with macular atrophy (MA) incidence in
      neovascular age-related macular degeneration treated with either ranibizumab or
      aflibercept in an Observe-and-Plan variable dosing regimen. METHODS: Information
      was obtained from two identical prospective treatment protocols using ranibizumab
      or aflibercept in a variable dosing regimen termed "Observe and Plan." Eyes
      without MA at baseline were included. New atrophy at the final 2-year visit was
      investigated with univariate and multivariate analysis to identify associated
      risk factors, focusing on treatment factors. RESULTS: De novo MA developed in 63
      (42%) of 149 eyes/patients (mean age 79.0 years), in 70 eyes treated using
      aflibercept and 79 eyes using ranibizumab. The univariate analysis showed
      multiple associations of MA with baseline factors, of which the following were
      confirmed as independent risk factors after multivariate stepwise logistic
      regression: lower number of anti-vascular endothelial growth factors injections
      (P = 0.011), depigmentation (P = 0.0004), reticular pseudodrusen (P = 0.0005),
      lower baseline visual acuity (P = 0.0006), and retinal angiomatous proliferation
      (P = 0.001). The drug type showed no significant association with MA incidence (P
      = 0.21). CONCLUSION: Within the variable dosing regimen, MA incidence was higher
      when fewer injections were required. More injections, if required by disease
      activity, did not increase the risk for MA.This is an open-access article
      distributed under the terms of the Creative Commons Attribution-Non Commercial-No
      Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and
      share the work provided it is properly cited. The work cannot be changed in any
      way or used commercially without permission from the journal.

PMID- 29370036
TI  - OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
      EVALUATION OF COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM.
AB  - PURPOSE: To study multimodal imaging features of combined hamartoma of the retina
      and retinal pigment epithelium (CHRRPE). METHODS: Six patients (3 males, mean age
      11 years) and a healthy age-matched control group made up of 15 healthy subjects
      (8 males, mean age 12.6 years) were included in the analysis. Complete
      ophthalmologic examination was performed, including best-corrected visual acuity,
      anterior and posterior segment slit-lamp evaluation, and tonometry. The
      multimodal imaging protocol included fundus images, structural optical coherence
      tomography (OCT), and swept-source OCT angiography (OCTA). The main outcome
      measures included the qualitative evaluation of both OCT and OCTA features of
      CHRRPE, retinal and choroidal thickness measurements, and the quantitative
      analysis of superficial capillary plexus, deep capillary plexus, and
      choriocapillaris vessel densities. RESULTS: Optical coherence tomography features
      of CHRRPE were examined extensively. Multiple little hyperreflective triangular
      outer retinal alterations were found at the CHRRPE edges in all patients; these
      were dubbed the "shark-teeth" sign. Optical coherence tomography angiography
      showed rarefaction and morphologic alterations of all retinal plexa. Moreover,
      quantitative analysis revealed a statistically significant decrease in
      superficial capillary plexus, deep capillary plexus, and choriocapillaris vessel
      densities in patients affected by CHRRPE compared with the control group.
      CONCLUSION: Optical coherence tomography and OCTA analyses allowed the accurate
      qualitative and quantitative analyses of CHRRPE features. Further studies are
      needed to better define OCTA changes of CHRRPE better and to improve our
      understanding of the possible causes of the shark-teeth sign.

PMID- 29370037
TI  - Visualization of Lamellar Hole-Associated Epiretinal Proliferation With Blue
      Reflectance Imaging.

PMID- 29370038
TI  - Committee Opinion No. 485: Prevention of Early-Onset Group B Streptococcal
      Disease in Newborns: Correction.

PMID- 29370039
TI  - Connect the Dots-December 2017: Correction.

PMID- 29370040
TI  - Quality of Life and Sexual Function 2 Years After Vaginal Surgery for Prolapse:
      Second Correction.

PMID- 29370043
TI  - ACOG Publications.

PMID- 29370044
TI  - ACOG Practice Bulletin No. 190 Summary: Gestational Diabetes Mellitus.
AB  - Gestational diabetes mellitus (GDM) is one of the most common medical
      complications of pregnancy. However, debate continues to surround the diagnosis
      and treatment of GDM despite several recent large-scale studies addressing these
      issues. The purposes of this document are the following: 1) provide a brief
      overview of the understanding of GDM, 2) review management guidelines that have
      been validated by appropriately conducted clinical research, and 3) identify gaps
      in current knowledge toward which future research can be directed.

PMID- 29370045
TI  - ACOG Practice Bulletin No. 191 Summary: Tubal Ectopic Pregnancy.
AB  - Ectopic pregnancy is defined as a pregnancy that occurs outside of the uterine
      cavity. The most common site of ectopic pregnancy is the fallopian tube. Most
      cases of tubal ectopic pregnancy that are detected early can be treated
      successfully either with minimally invasive surgery or with medical management
      using methotrexate. However, tubal ectopic pregnancy in an unstable patient is a
      medical emergency that requires prompt surgical intervention. The purpose of this
      document is to review information on the current understanding of tubal ectopic
      pregnancy and to provide guidelines for timely diagnosis and management that are
      consistent with the best available scientific evidence.

PMID- 29370046
TI  - ACOG Committee Opinion No. 730 Summary: Fatigue and Patient Safety.
AB  - Fatigue and sleep deprivation may affect a health care provider's skills and
      communication style, and also may affect clinical outcomes. The National Sleep
      Foundation recommends 7-9 hours of sleep per night for an adult. However, there
      are no current guidelines limiting the volume of deliveries and procedures
      performed by a single individual or on the length of time he or she may be on
      call. Medical literature has shown that even a single night of missed sleep
      measurably affects cognitive performance. When adults do not sleep at least 5
      hours per night, language and numeric skills, retention of information, short
      term memory, and concentration all decrease on standardized testing. Speed of
      performance may be affected more than accuracy. Sleep deprivation may affect mood
      to a greater degree than it affects cognitive or motor performance, and, thus,
      may have a significant effect on a physician's ability to communicate
      effectively. To help mitigate resident fatigue, programs must train all faculty
      members and residents to recognize the signs of fatigue and sleep deprivation.
      The medical directors of outpatient units and chairs of hospital departments of
      obstetrics and gynecology may consider developing call schedules and associated
      policies that balance the need for continuity of care and the health care
      providers' need for rest. Designing standardized procedures also may protect
      against fatigue-related errors. Physicians at all stages in their careers need to
      be conscious of the demands placed on them professionally and personally and
      should balance those demands with rest to avoid excessive fatigue or
      overcommitment.

PMID- 29370047
TI  - ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus.
AB  - Gestational diabetes mellitus (GDM) is one of the most common medical
      complications of pregnancy. However, debate continues to surround the diagnosis
      and treatment of GDM despite several recent large-scale studies addressing these
      issues. The purposes of this document are the following: 1) provide a brief
      overview of the understanding of GDM, 2) review management guidelines that have
      been validated by appropriately conducted clinical research, and 3) identify gaps
      in current knowledge toward which future research can be directed.

PMID- 29370048
TI  - ACOG Committee Opinion No. 730: Fatigue and Patient Safety.
AB  - Fatigue and sleep deprivation may affect a health care provider's skills and
      communication style, and also may affect clinical outcomes. The National Sleep
      Foundation recommends 7-9 hours of sleep per night for an adult. However, there
      are no current guidelines limiting the volume of deliveries and procedures
      performed by a single individual or on the length of time he or she may be on
      call. Medical literature has shown that even a single night of missed sleep
      measurably affects cognitive performance. When adults do not sleep at least 5
      hours per night, language and numeric skills, retention of information, short
      term memory, and concentration all decrease on standardized testing. Speed of
      performance may be affected more than accuracy. Sleep deprivation may affect mood
      to a greater degree than it affects cognitive or motor performance, and, thus,
      may have a significant effect on a physician's ability to communicate
      effectively. To help mitigate resident fatigue, programs must train all faculty
      members and residents to recognize the signs of fatigue and sleep deprivation.
      The medical directors of outpatient units and chairs of hospital departments of
      obstetrics and gynecology may consider developing call schedules and associated
      policies that balance the need for continuity of care and the health care
      providers' need for rest. Designing standardized procedures also may protect
      against fatigue-related errors. Physicians at all stages in their careers need to
      be conscious of the demands placed on them professionally and personally and
      should balance those demands with rest to avoid excessive fatigue or
      overcommitment.

PMID- 29370049
TI  - The changing role of endovascular stenting for blunt cerebrovascular injuries.
AB  - BACKGROUND: Few injuries have produced as much debate with respect to management
      as have blunt cerebrovascular injuries (BCVIs). Without question, early
      anticoagulation is the mainstay of therapy for these injuries. However, the role
      of endovascular stenting for BCVI remains controversial. Our purpose was to
      examine the use of endovascular stents for BCVI and outcomes and describe which
      injuries are being treated with stents. METHODS: Patients with BCVI from 2011 to
      2016 were identified and stratified by age, sex, and injury severity. Patients
      were then divided into two groups (previous study [PS] = 2011-2012 and current
      study [CS] = 2013-2016) based on a paradigm shift in BCVI diagnosis and treatment
      at our institution. Beginning in 2013, a multidisciplinary team assumed care of
      patients with BCVI from interventional radiology. Digital subtraction angiography
      was used to confirmatory injuries in both groups and heparin used for initial
      therapy. RESULTS: In the CS, 237 patients were diagnosed with BCVI compared with
      128 patients in the PS. Both groups were clinically similar with no difference in
      distribution of vessels injured. Beginning in 2013, there was a significant
      decrease in the use of stents for these injuries. In fact, in the CS, only 21
      (8.9%) patients were treated with endovascular stenting compared to 44 (34%)
      patients in the PS. Of patients in the CS, 14 had grade III pseudoaneurysms and
      seven had grade II dissections. Despite this reduction in stenting, there was no
      significant change in the BCVI-related stroke rate between the CS and the PS
      (4.2% vs. 3.9%). CONCLUSION: Anticoagulation alone is adequate therapy for the
      majority of BCVI. Nevertheless, there is still a role for endovascular stents in
      the treatment of BCVI. Their use should be reserved for enlarging carotid
      pseudoaneurysms and dissections with significant narrowing. The prospect of
      determining which injuries benefit from stent placement warrants prospective
      investigation. LEVEL OF EVIDENCE: Therapuetic/care management, level IV.

PMID- 29370050
TI  - Impact of venorrhaphy and vein ligation in isolated lower-extremity venous
      injuries on venous thromboembolism and edema.
AB  - BACKGROUND: Following venous injury, venorrhaphy can restore outflow, although it
      risks thrombosis and venous thromboembolism (VTE). Vein ligation is a faster
      option, although it potentially risks extremity edema. The purpose of this study
      was to evaluate the management of venous injury on VTE and extremity edema in
      patients with isolated lower-extremity venous injuries. METHODS: Patients with
      common iliac, external iliac, and femoral venous injuries over a 10-year period
      were stratified by age, shock, management of venous injury, injury severity, and
      timing and type of anticoagulation. Outcomes included development of extremity
      edema and VTE (pulmonary embolism, deep venous thrombosis). Outcomes were then
      evaluated to determine risk factors for symptomatic lower-extremity edema and VTE
      by the management of venous injuries. RESULTS: Eighty-four patients were
      identified: 20 common iliac, 27 external iliac, 37 femoral. Forty-nine underwent
      vein repair and 35 underwent vein ligation. Ninety-three percent were male with a
      mean Injury Severity Score and Glasgow Coma Scale score of 17 and 14,
      respectively. Venous thromboembolism occurred in 18 (21%), 15 (18%) deep venous
      thrombosis, and 4 (5%) pulmonary embolisms. Thirty-two (38%) patients developed
      lower-extremity edema. Those who underwent vein ligation had a greater degree of
      shock on presentation (RBC transfusions, 14 vs. 8 units; p = 0.03) and were more
      likely to receive prophylactic fasciotomies (60% vs. 33%, p = 0.01). There was no
      difference in time to or type of chemoprophylaxis between patients who underwent
      vein repair and those who received vein ligation. However, patients with vein
      ligation had fewer episodes of VTE (9% vs. 31%, p = 0.02) with no difference in
      symptomatic lower-extremity edema (37% vs. 39%, p = 0.88) or amputation rates (0%
      vs. 2%, p = 0.99). CONCLUSION: Vein repair had a higher incidence of VTE while
      providing no additional benefit in reducing symptomatic extremity edema compared
      to ligation in patients suffering venous injury. Ligation of most extremity
      venous injuries can be performed without increasing patient morbidity. LEVEL OF
      EVIDENCE: Therapeutic study, level IV.

PMID- 29370051
TI  - A protocol for non-operative management of uncomplicated appendicitis.
AB  - BACKGROUND: We developed a protocol to identify candidates for non-operative
      management (NOM) of uncomplicated appendicitis. Our objective was to evaluate
      protocol efficacy with the null hypothesis that clinical outcomes, hospital
      readmission rates, and hospital charges would be unchanged after protocol
      implementation. METHODS: We performed a single-center 4-year propensity score
      matched retrospective cohort analysis of 406 patients with acute uncomplicated
      appendicitis. The protocol recommended NOM for patients with modified Alvarado
      score <=6 and no appendicolith. Patients admitted before (n = 203) and after (n =
      203) protocol implementation were matched by Charlson comorbidity index, duration
      of symptoms, and modified Alvarado score. Outcomes included operative management,
      days on antibiotic therapy, length of stay, and hospital charges, as well as
      readmissions, complications, and mortality within 180 days. RESULTS: Baseline
      characteristics were similar between groups (age 31 years, ASA class 2.0,
      Charlson comorbidity index 0.0). Protocol compliance was higher when the protocol
      recommended appendectomy (97%) rather than NOM (73%, p < 0.001). The incidence of
      operative management decreased from 99% to 82% after protocol implementation (p <
      0.001). In the protocol group, there was a lower incidence of open surgery (4%
      vs. 10%, p = 0.044) despite a longer interval between admission and surgery (8.6
      vs. 7.1 hours, p < 0.001). After protocol implementation, 51 patients had NOM: 18
      failed NOM during admission and 6 failed NOM after discharge. Compared to the pre
      protocol group, the protocol group had similar length of stay, antibiotic days,
      and overall complication rates, but more readmissions (6% vs. 1%, p = 0.019) and
      lower hospital charges for the index admission ($5,630 vs. $6,878, p < 0.001).
      CONCLUSIONS: Implementation of a protocol to identify candidates for NOM of acute
      uncomplicated appendicitis was associated with lower rates of open surgery, fewer
      appendectomies, decreased hospital charges, and no difference in overall
      complications despite high rates of readmission and failure of NOM. LEVEL OF
      EVIDENCE: Therapeutic study, level IV.

PMID- 29370052
TI  - Implementation of a National Trauma Research Action Plan (NTRAP).

PMID- 29370053
TI  - A review of the landscape: Challenges and gaps in trauma response to civilian
      high threat mass casualty incidents.
AB  - The ultimate goal of the emergency response and trauma system is to reduce
      potentially preventable death from trauma. Tremendous advances in trauma care
      emerged from the past 15 years of United States' combat engagements around the
      globe. Unfortunately, combat and insurgency tactics have also metastasized to the
      civilian world, resulting in increasingly complex and dynamic acts of intentional
      mass violence. These high threat active violent incidents (AVIs) pose significant
      preparedness, response, and clinical care challenges to the civilian healthcare
      systems. Currently, there are several operational and policy gaps that limit the
      successful preparedness and response to AVIs and dynamic MCIs in the United
      States.

PMID- 29370054
TI  - Staff officers as blood suppliers: Effects of repeated donations and autologous
      reinfusions of untransfused units.
AB  - BACKGROUND: Limited blood inventory and resupply chains in combat settings can
      result in preventable deaths from traumatic hemorrhage. One way of mitigating
      this could be to establish donor pools where blood is collected in advance of
      high-risk missions and then reinfused back to the donor if not needed to treat
      casualties. METHODS: Four hundred fifty milliliters plus 56 mL of blood was
      collected, rested for 2 hours in room temperature, and stored at 4 degrees C. The
      blood was reinfused 22 to 24 hours after donation and the donor observed for
      adverse reactions. Samples were collected before and 20 minutes after each
      donation for hematology, immunoglobulin G, ferritin, C-reactive protein, total
      protein, lactate dehydrogenase, bilirubin, haptoglobin, and activated partial
      thromboplastin time. RESULTS: Nine participants went through a total of 36
      donation and reinfusion procedures. Four donors participated in five rounds, two
      in four rounds, two in three rounds, and one in two rounds. A significant drop
      was seen in hemoglobin (14.6 +/- 0.9 to 13.9 +/- 0.9) and ferritin (179 +/- 70 to
      149 +/- 78) from before the first donation to after the last reinfusion (p <
      0.05). Other parameters were unaffected. CONCLUSION: This small pilot study
      suggests that repeated donations and reinfusions may be both feasible and safe.
      Blood collected in this way should be labeled with the donor's full name and
      social security number (or similar) and the identity visually verified by the
      donor immediately before both donation and reinfusion. To further reduce risk,
      this form of donation should be restricted to scenarios where there is no other
      option for making blood available. LEVEL OF EVIDENCE: Therapeutic/Care management
      study, level V.

PMID- 29370055
TI  - The modified Veress needle for tension pneumothorax.

PMID- 29370056
TI  - The history and promising future of phage therapy in the military service.
AB  - The continuous evolvement of bacterial resistance to most, if not all, available
      antibiotics is a worldwide problem. These strains, frequently isolated from
      military-associated environments, have created an urgent need to develop
      supplementary anti-infective modalities. One of the leading directions is phage
      therapy, which includes the administration of bacteriophages, viruses that
      specifically target bacteria, as biotherapies. Although neglected in the West
      until recent years, bacteriophages have been widely studied and clinically
      administered in the former Soviet Union and Eastern Europe for over a century,
      where they were found to be incredibly efficient at battling numerous infectious
      diseases.In this review, we discuss the high potential of phage therapy as a
      solution for resistant bacterial infectious diseases relating to military
      medicine. By describing the historical development and knowledge acquired on
      phage therapy, we define the advantages of bacteriophages for combating resistant
      bacteria in multiple settings, such as trauma injuries and foodborne illnesses,
      as a preventive tool and therapy against biological warfare agents, and more. We
      also present the most recent successful clinical applications of bacteriophages
      in military settings worldwide.We believe that augmenting military medicine by
      integrating phage therapy is an important and required step in preparedness for
      the rapidly approaching post-antibiotic era.

PMID- 29370057
TI  - Analysis of isolated transverse process fractures sustained during blast-related
      events.
AB  - BACKGROUND: Personnel have sustained a range of devastating blast injuries during
      recent conflicts. Previous studies have focused on severe injuries, including to
      the spine; however, no study has specifically focused on the most common spinal
      injury-transverse process (TP) fractures. Although their treatment usually
      requires limited intervention, analysis of TP fractures may help determine injury
      mechanisms. METHODS: Data were collected from victims with spinal fractures who
      were injured in improvised explosive device attacks, from the UK's Joint Theatre
      Trauma Registry. The level and side of each TP fracture were recorded, as well as
      associated injuries, whether they were mounted or dismounted, and outcome
      (survivor or fatality). RESULTS: Most (80%) of the TP fractures were lumbar. More
      bilateral (both left and right fractures at the same level), and L5 TP fractures,
      were seen in fatalities than survivors. In the mounted group, lumbar TP fractures
      were statistically significantly associated with fatality, head injury,
      noncompressible torso hemorrhage, pelvic injury, and other spinal injuries. In
      the dismounted group, thoracic TP fractures were associated with head, chest
      wall, and other spinal injuries; and lumbar TP fractures were associated with
      pelvic and other spinal injuries. CONCLUSIONS: Different injury mechanisms of the
      TP in the mounted and dismounted groups are likely. Inertial forces acting within
      the torso due to rapid loading being transferred through the seat, or high intra
      abdominal pressures causing the tensile forces acting through the lumbar fascia
      to avulse the TPs are likely mechanisms in the mounted group. Blunt trauma,
      violent lateral flexion-extension forces, or rapid flail of the lower extremities
      causing tension of the psoas muscle, avulsing the TP, are likely causes in the
      dismounted group. Isolated lumbar TP fractures can be used as markers for more
      severe injuries, and fatality, in mounted blast casualties. LEVEL OF EVIDENCE:
      Prognostic and epidemiological, level III.

PMID- 29370058
TI  - Permissive hypotension versus conventional resuscitation strategies in adult
      trauma patients with hemorrhagic shock: A systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Aggressive fluid resuscitation in trauma promotes deleterious effects
      such as clot disruption, dilutional coagulopathy and hypothermia. Animal studies
      suggest that permissive hypotension maintains appropriate organ perfusion,
      reduces bleeding and improves mortality. This review assesses the efficacy and
      safety of permissive hypotension in adult trauma patients with hemorrhagic shock.
      METHODS: We searched the MEDLINE and EMBASE databases from inception to May 2017
      for randomized controlled trials comparing permissive hypotension vs.
      conventional resuscitation following traumatic injury. We included preoperative
      and intraoperative resuscitation strategies. The primary outcome was 30-day or in
      hospital mortality. Secondary outcomes included blood product utilization,
      estimated blood loss and in-hospital complications. Pooling was performed with a
      random-effects model. RESULTS: We screened 722 abstracts, from which five
      randomized trials evaluating 1,158 patients were included. Blood pressure targets
      in the intervention arms varied from systolic BP 50 mm Hg to 70 mm Hg or mean
      arterial pressure of 50 mm Hg or higher as compared to systolic BP 65 mm Hg to
      100 mm Hg or mean arterial pressure of 65 or higher in the control arms. Two
      studies evaluated only patients with penetrating injury while the remaining three
      additionally included blunt injuries. Four trials suggested a survival benefit
      for 30-day or in-hospital mortality with hypotensive resuscitation, although
      three studies were insufficiently powered to find statistical significance.
      Studies were of poor to moderate quality due to poor protocol reporting and lack
      of blinding. The pooled odds ratio was 0.70 (95% confidence interval, 0.53-0.92),
      suggesting a survival benefit for permissive hypotension. Those patients received
      fewer blood products and had lesser estimated blood loss. CONCLUSION: Permissive
      hypotension may offer a survival benefit over conventional resuscitation for
      patients with hemorrhagic injury. It may additionally reduce blood loss and blood
      product utilization. However, the majority of studies were underpowered, thus
      reflecting a need for high quality, adequately powered trials. PROSPERO
      REGISTRATION: Systematic Review, level II.CRD42017070526.

PMID- 29370059
TI  - Avoiding Cribari gridlock: The standardized triage assessment tool improves the
      accuracy of the Cribari matrix method in identifying potential overtriage and
      undertriage.
AB  - BACKGROUND: The Cribari matrix method (CMM) is the standard to identify potential
      overtriage and undertriage but requires case reviews to correct for the fact that
      Injury Severity Score does not account for physiology or comorbidities, nor is it
      well correlated with resource consumption. Further, the secondary reviews
      introduce undesirable subjectivity. This study assessed if the Standardized
      Triage Assessment Tool (STAT)-a combination of the CMM and the Need For Trauma
      Intervention-could more accurately determine overtriage and undertriage than the
      CMM alone. METHODS: The registry of an American College of Surgeons verified
      Level I adult trauma center in Texas was queried for all new emergency department
      traumas 2013 to 2016 (n = 11,110). Binary logistic regressions were used to test
      the associations between the triage determinations of each metric against
      indicators of injury severity (risk factors, complications, and mortality) and
      resource consumption (number of procedures in 3 days and total length of stay).
      RESULTS: Both metrics were associated with the indicators of injury severity and
      resource consumption in the expected directions, but STAT had stronger or
      equivalent associations with all variables tested. Using the CMM, there was 50.4%
      overtriage and 9.1% undertriage. Using STAT, overtriage was reduced to 30.8%
      (relative reduction = 38.9%) and undertriage was reduced to 3.3% (relative
      reduction = 63.7%). CONCLUSION: Using the CMM with secondary case reviews makes
      valid multi-institutional triage rate comparisons impossible because of the
      subjective and unstandardized nature of these reviews. STAT's out-of-box triage
      determinations (i.e., without manual case review) outperformed CMM in almost
      every tested variable for both over- and undertriage. STAT, an automatic,
      standardized method offers significant improvements compared to the current
      subjective system. Further, by accounting for both anatomic injury severity and
      resource consumption, STAT may allow trauma centers to better allocate resources
      and predict patient needs with fewer cases requiring manual review. LEVEL OF
      EVIDENCE: Prognostic, level III.

PMID- 29370060
TI  - Trauma transitional care coordination: A mature system at work.
AB  - BACKGROUND: We have previously demonstrated effectiveness of a Trauma
      Transitional Care Coordination (TTCC) Program in reducing 30-day readmission
      rates for trauma patients most at risk. With program maturation, we achieved
      improved readmission rates for specific patient populations. METHODS: TTCC is a
      nursing driven program that supports patients at high risk for 30-day
      readmission. The TTCC interventions include calls to patients within 72 hours of
      discharge, complete medication reconciliation, coordination of medical
      appointments, and individualized problem solving. Account IDs were used to link
      TTCC patients with the Health Services Cost Review Commission database to collect
      data on statewide unplanned 30-day readmissions. RESULTS: Four hundred seventy
      five patients were enrolled in the TTCC program from January 2014 to September
      2016. Only 10.5% (n = 50) of TTCC enrollees were privately insured, 54.5% had
      Medicaid (n = 259), and 13.5% had Medicare (n = 64). Seventy-three percent had
      Health Services Cost Review Commission severity of injury ratings of 3 or 4
      (maximum severity of injury = 4). The most common All Patient Refined Diagnosis
      Related Groups for participants were: lower-extremity procedures (n = 67, 14%);
      extensive abdominal/thoracic procedures (n = 40, 8.4%); musculoskeletal
      procedures (n = 37, 7.8%); complicated tracheostomy and upper extremity
      procedures (n = 29 each, 6.1%); infectious disease complications (n = 14, 2.9%);
      major chest/respiratory trauma, major small and large bowel procedures and
      vascular procedures (n = 13 each, 2.7%). The TTCC participants with lower
      extremity injury, complicated tracheostomy, and bowel procedures had 6-point
      reduction (10% vs. 16%, p = 0.05), 11-point reduction (13% vs. 24%, p = 0.05),
      and 16-point reduction (11% vs. 27%, p = 0.05) in 30-day readmission rates,
      respectively, compared to those without TTCC. CONCLUSION: Targeted outpatient
      support for high-risk patients can decrease 30-day readmission rates. As our TTCC
      program matured, we reduced 30-day readmission in patients with lower-extremity
      injury, complicated tracheostomy and bowel procedures. This represents over one
      million-dollar savings for the hospital per year through quality-based
      reimbursement. LEVEL OF EVIDENCE: Therapeutic/care management, level III.

PMID- 29370061
TI  - Temporary ectopic implantation for salvaging amputated parts: A systematic
      review.
AB  - BACKGROUND: Temporary ectopic implantation is an option when handling severe
      crushing injuries to the distal extremities or other body parts. The surgical
      techniques applied in those cases, and the patient outcomes have not been
      previously analyzed. METHODS: Extensive literature search was performed using
      PubMed, EMBASE, and Google Scholar to collect articles reporting outcomes of
      temporary ectopic implantation for salvaging amputated extremities or other body
      parts. Age and sex of patients, injured part, amputation level, surgical details,
      and clinical outcomes were recorded. RESULTS: Twenty-two articles encompassing 38
      amputated cases met the inclusion criteria. The publication dates ranged from
      1986 to 2016. Of the 38 cases, temporary ectopic implantation procedures were
      performed in 16 digit cases, 10 hand cases, 3 forearm cases, 5 foot cases, 1
      penis case, 1 testes case, and 2 scalp cases. The ectopic implantation duration
      varied from 6 to 319 days. The ectopic implantation and following replantation of
      the amputated parts resulted in a survival rate of 81.6% and 100%, respectively.
      With different follow-up durations, most patients were found to have sensation
      restore in the tips of reconstructed extremities, and those reconstructed
      extremities were functionally useful in daily lives. The function of other
      replanted parts was also satisfactory. CONCLUSION: Temporary ectopic implantation
      is a valuable technique for salvaging amputation cases resulted from severe
      crushing injuries. There is yet no consensus on the indications of this surgical
      technique. In future practices, both success and failure cases should be recorded
      and analyzed to help us to optimize the surgical strategies and improve the
      patient outcomes. LEVEL OF EVIDENCE: Systematic review, level IV.

PMID- 29370062
TI  - Maximizing geographical efficiency: An analysis of the configuration of
      Colorado's trauma system.
AB  - BACKGROUND: Trauma center designation in excess of need risks dilution of
      experience, reduction in research and training opportunities, and increased
      costs. The objective of this study was to evaluate the use of a novel data-driven
      approach (whole-system mathematical modeling of patient flow) to compare the
      configuration of an existing trauma system with a mathematically optimized
      design, using the State of Colorado as a case study. METHODS: Geographical
      network analysis and multiobjective optimization, 105,448 patients injured in the
      State of Colorado between 2009 and 2013, who met the criteria for inclusion in
      the state-mandated trauma registry maintained by the Colorado Department of
      Public Health and Environment were included. We used the Nondominant Sorting
      Genetic Algorithm II to conduct a multiobjective optimization of possible trauma
      system configurations, with the objectives of minimizing total system access
      time, and the number of casualties who could not reach the desired level of care.
      RESULTS: Modeling suggested that system configurations with high-volume Level I
      trauma centers could be mathematically optimized with two centers rather than the
      current three (with an estimated annual volume of 970-1,020 and 715-722 severely
      injured patients per year), four to five Level II centers, and 12 to 13 Level III
      centers. Configurations with moderate volume Level I centers could be optimized
      with three such centers (with estimated institutional volumes of 439-502, 699
      947, and 520-726 severely injured patients per year), two to five Level II
      centers, and eight to ten Level III centers. CONCLUSION: The modeling suggested
      that the configuration of Colorado's trauma system could be mathematically
      optimized with fewer trauma centers than currently designated. Consideration
      should be given to the role of optimization modeling to inform decisions about
      the ongoing efficiency of trauma systems. However, modeling on its own cannot
      guarantee improved patient outcome; thus, the use of model results for decision
      making should take into account wider contextual information. LEVEL OF EVIDENCE:
      Epidemiological, Level IV.

PMID- 29370063
TI  - Fresh whole blood resuscitation does not exacerbate skeletal muscle edema and
      long-term functional deficit after ischemic injury and hemorrhagic shock.
AB  - BACKGROUND: Hemorrhagic shock caused by extremity vascular injuries is common in
      combat injuries. Fluid resuscitation is the standard treatment for severe
      hemorrhage (HEM). Tourniquets (TKs) used for HEM control cause ischemia
      reperfusion (I/R) injury that induces edema formation in the injured muscle.
      Resuscitation fluids affect edema formation; however, its effect on long-term
      functional response remains unknown. The objectives of this study are to (1)
      compare acute muscle damage; (2) determine long-term functional recovery of
      ischemic muscle; and (3) compare local and systemic inflammatory response
      including the expression of junctional proteins following early resuscitation
      with Hextend and fresh whole blood using a rodent model of combined HEM and TK
      induced limb I/R. METHODS: Anesthetized Sprague-Dawley rats underwent 42.5%
      arterial HEM, followed by 3 hours of TK application. Animals were either not
      resuscitated or resuscitated with Hextend or fresh whole blood. Two time points
      were evaluated, 2 and 28 days. Plasma cytokine concentrations were determined at
      baseline and end resuscitation. At 2 days, edema formation, expression of
      junctional proteins, and tissue level cytokines concentrations were evaluated. At
      28 days, in vivo muscle contractile properties were determined. At both time
      points, routine histology was performed and graded using a semiquantitative
      grading system. RESULTS: All animals developed hemorrhagic hypovolemia; the
      mortality rate was 100% in nonresuscitated rats. Hextend resuscitation
      exacerbated muscle edema (~11%) and muscle strength deficit (~20%). Fresh whole
      blood resuscitation presented edema and muscle strength akin to TK only. Fresh
      whole blood resuscitation upregulated expression of junctional proteins including
      proangiogenic factors and dampened the inflammatory response. CONCLUSION: Fresh
      whole blood resuscitation does not exacerbate either TK-induced edema or muscle
      strength deficit. Fresh whole blood resuscitation may reduce both acute and long
      term morbidity associated with extremity trauma. To our knowledge, this is the
      first study to demonstrate the nature of the resuscitation fluid administered
      following HEM impacts short- and long-term indices of I/R in skeletal muscle.

PMID- 29370064
TI  - Functional stability of the TEG 6s hemostasis analyzer under stress.
AB  - BACKGROUND: Viscoelastic measurements of coagulation provide much needed
      information, including guidance for triage and insight into bleeding disorders.
      The current clinical standards for these devices are the thromboelastogram (TEG)
      5000 and the rotational thromboelastometer (ROTEM) delta, but a new product, the
      TEG 6s, has recently come to market, designed to simplify the user experience,
      reduce the required blood volume, and conduct multiple assays simultaneously.
      This study compares the performance of these three devices and examines the
      resiliency of the TEG 6s under various stresses. METHODS: The variances of
      coagulation metrics obtained by the TEG 6s (prototype and production models), TEG
      5000, and ROTEM delta were compared using manufacturers' reagents and citrate
      collected blood from healthy donors. Variability between devices was examined,
      and their performances under various motion and temperature stresses were
      compared by placing one unit on a linear or orbital shaker, in the cold, or in
      the heat while a counterpart remained stationary at room temperature. RESULTS:
      Although most comparable parameters had low degrees of variance, there were small
      but significantly increased variances found in some ROTEM delta and TEG 5000
      parameters versus comparable TEG 6s parameters. Orbital rotation of the TEG 6s
      had no effect on means of any parameter but resulted in increased variance of 2
      parameters, but linear motion with sudden striking had no observed impact on
      results. Similarly, 7-day exposure to heat (45 degrees C) or cold (4 degrees C)
      only resulted in minor deviations within normal ranges of the TEG 6s. DISCUSSION:
      The TEG 6s provides several improvements over other coagulation analyzers: it is
      easier to use and robustly resilient against motion and temperature stresses.
      These features suggest that it may be capable of deployment not only in the
      clinical laboratory but also to a variety of austere settings. LEVEL OF EVIDENCE:
      Diagnostic test, level III.

PMID- 29370065
TI  - How has the Affordable Care Act changed outcomes in emergency general surgery?
AB  - INTRODUCTION: Lack of insurance coverage increases complications and mortality
      from surgical procedures. The 2014 Affordable Care Act (ACA) Open Enrollment (OE)
      insured more Americans, but it is unknown if this improved outcomes from
      emergency general surgery (EGS) procedures. This study seeks to determine how ACA
      OE coverage changes outcomes in EGS. METHODS: This is a retrospective review
      using the Nationwide Inpatient Sample database from 2012 to 2014. Patients aged
      18 to 64 years undergoing EGS procedures were identified by International
      Classification of Diseases, Ninth Revision, codes. Medicare patients were
      excluded. Patient demographics, hospital characteristics, and Charlson
      comorbidity index were obtained. Outcomes were measured by mortality,
      complications, and calculated costs. Univariate and difference-in-differences
      multivariate analyses were performed to determine the effect of the ACA OE on EGS
      outcomes. RESULTS: A total of 304,110 EGS cases were identified. After Medicare
      patients were excluded, there were 275,425 cases. In 2014, Medicaid admissions
      increased 18.2% from 18,495 to 22,615 (p < 0.001) and self-pay admissions
      decreased 33% from 14,938 to 10,630 (p < 0.001). Mortality significantly
      increased for self-pay patients in 2014 from 0.81% to 1.22% (p < 0.001).
      Difference-in-differences analysis indicated that, after risk adjustment, the ACA
      OE was associated with a small reduction in mortality for insured patients (
      0.12%, p = 0.034), increased complications (1.4%, p = 0.009), and increased wage
      index adjusted mean costs (4.6%, p < 0.001). There was a significant increase in
      Medicare (+26.5%) and private (+12.2%, p < 0.001) insurance admissions in
      teaching hospitals, while nonteaching hospitals had fewer EGS admissions with a
      greater reduction in uninsured EGS admissions. CONCLUSIONS: The ACA OE created a
      significant reduction in uninsured EGS admissions but did not reduce EGS
      mortality. Mortality decreased in insured patients but increased in uninsured
      patients, indicating that the ACA OE primarily insured lower-risk patients. The
      ACA OE did increase cost and complications in insured admissions. Teaching
      hospitals saw the majority of the increase in Medicaid and private insurance EGS
      admissions. A national registry would improve future study of insurance policy on
      EGS outcomes. LEVEL OF EVIDENCE: Economic analysis, level IV.

PMID- 29370066
TI  - Abdominal trauma surgery during recent US combat operations from 2002 to 2016.
AB  - BACKGROUND: Abdominal surgery constitutes approximately 13% of surgical
      procedures performed for combat injuries. This study examines the frequencies and
      type of abdominal surgical procedures performed during recent US Military
      operations. METHODS: A retrospective analysis of the Department of Defense Trauma
      Registry was performed for all Role 2 (R2) and Role 3 (R3) medical treatment
      facilities (MTFs), from January 2002 to May 2016. The 273 International
      Classification of Diseases, Ninth Revision, Clinical Modification procedure codes
      that were identified as abdominal surgical procedures were stratified into 24
      groups based on anatomic and functional classifications and then grouped by
      whether they were laparoscopic. Procedure grouping and categorization were
      determined, and adjudicated if necessary, by subject matter experts. Data
      analysis used Stata version 14 (College Station, TX). RESULTS: A total of 26,548
      abdominal surgical procedures were identified at R2 and R3 MTFs. The majority of
      abdominal surgical procedures were reported at R3 facilities. The largest
      procedure group at both R2 and R3 MTFs were procedures involving the bowel. There
      were 18 laparoscopic procedures reported (R2: 4 procedures, R3: 14 procedures).
      Laparotomy not otherwise specified was the second largest procedure group at both
      R2 (1,060 [24.55%]) and R3 (4,935 [22.2%]) MTFs. Abdominal caseload was variable
      over the 15-year study period. CONCLUSIONS: Surgical skills such as open
      laparotomy and procedures involving the bowel are crucial in war surgery. The
      abundance of laparotomy not otherwise specified may reflect inadequate
      documentation, or the plethora of second- and third-look operations and washouts
      performed for complex abdominal injuries. Traditional elective general surgical
      cases (gallbladder, hernia) were relatively infrequent. Laparoscopy was almost
      nonexistent. Open abdominal surgical skills therefore remain a necessity for the
      deployed US Military General Surgeons; this is at odds with the shifting paradigm
      from open to laparoscopic skills in stateside civilian and military hospitals.
      LEVEL OF EVIDENCE: Epidemiologic study, level III.

PMID- 29370067
TI  - Effect of door-to-angioembolization time on mortality in pelvic fracture: Every
      hour of delay counts.
AB  - INTRODUCTION: Angioembolization (AE) is widely used for hemorrhagic control in
      patients with pelvic fracture. The latest version of the Resources for Optimal
      Care of the Injured Patient issued by the American College of Surgeons Committee
      on Trauma requires interventional radiologists to be available within 30 minutes
      to perform an emergency AE. However, the impact of time-to-AE on patient outcomes
      remains unknown. We hypothesized that a longer time-to-AE would be significantly
      associated with increased mortality in patients with pelvic fracture. METHODS:
      This is a 2-year retrospective cohort study using the American College of
      Surgeons Trauma Quality Improvement Program database from January 2013 to
      December 2014. We included adult patients (age >= 18 years) with blunt pelvic
      fracture who underwent pelvic AE within 4 hours of hospital admission. Patients
      who required any hemorrhage control surgery for associated injuries within 4
      hours were excluded. Hierarchical logistic regression was performed to evaluate
      the impact of time-to-AE on in-hospital and 24-hour mortality. RESULTS: A total
      of 181 patients were included for analysis. The median age was 54 years
      (interquartile range, 38-68) and 69.6% were male. The median injury severity
      score was 34 (interquartile range, 27-43). Overall in-hospital mortality rate was
      21.0%. The median packed red blood cell transfusions within 4 and 24 hours after
      admission were 4 and 6 units, respectively. After adjusting for other covariates
      in a hierarchical logistic regression model, a longer time-to-pelvic AE was
      significantly associated with increased in-hospital mortality (odds ratio, 1.79
      for each hour; 95% confidence interval, 1.11-2.91; p = 0.018). CONCLUSION: The
      current study showed an increased risk of in-hospital mortality related to a
      prolonged time-to-AE for hemorrhagic control following pelvic fractures. Our
      results suggest that all trauma centers should allocate resources to minimize
      delays in performing pelvic AE. LEVEL OF EVIDENCE: Therapeutic/care management,
      level IV.

PMID- 29370068
TI  - Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the
      Formulation of APIs.
AB  - Cocrystals can be used as an alternative approach based on crystal engineering to
      enhance specific physicochemical and biopharmaceutical properties of active
      pharmaceutical ingredients (APIs) when the approaches to salt or polymorph
      formation do not meet the expected targets. In this article, an overview of
      pharmaceutical cocrystals will be presented, with an emphasis on the
      intermolecular interactions in cocrystals and the methods for their preparation.
      Furthermore, cocrystals of direct pharmaceutical interest, along with their in
      vitro properties and available in vivo data and characterization techniques are
      discussed, highlighting the potential of cocrystals as an attractive route for
      drug development.

PMID- 29370069
TI  - Tauroursodeoxycholic Acid Protects against the Effects of P-Cresol-Induced
      Reactive Oxygen Species via the Expression of Cellular Prion Protein.
AB  - Mesenchymal stem cells (MSCs) could be a promising solution in the treatment of
      various diseases including chronic kidney disease (CKD). However, endoplasmic
      reticulum (ER) stress induced by ischemia in the area of application limits the
      integration and survival of MSCs in patients. In our study, we generated ER
      stress-induced conditions in MSCs using P-cresol. As P-cresol is a toxic compound
      accumulated in the body of CKD patients and induces apoptosis and inflammation
      through reactive oxygen species (ROS), we observed ER stress-induced MSC
      apoptosis activated by oxidative stress, which in turn resulted from ROS
      generation. To overcome stress-induced apoptosis, we investigated the protective
      effects of tauroursodeoxycholic acid (TUDCA), a bile acid, on ER stress in MSCs.
      In ER stress, TUDCA treatment of MSCs reduced ER stress-associated protein
      activation, including GRP78, PERK, eIF2alpha, ATF4, IRE1alpha, and CHOP. Next, to
      explore the protective mechanism adopted by TUDCA, TUDCA-mediated cellular prion
      protein (PrPC) activation was assessed. We confirmed that PrPC expression
      significantly increased ROS, which was eliminated by superoxide dismutase and
      catalase in MSCs. These findings suggest that TUDCA protects from inflammation
      and apoptosis in ER stress via PrPC expression. Our study demonstrates that TUDCA
      protects MSCs against inflammation and apoptosis in ER stress by PrPC expression
      in response to P-cresol exposure.

PMID- 29370070
TI  - Study of Electronic Structure, Thermal Conductivity, Elastic and Optical
      Properties of alpha, beta, gamma-Graphyne.
AB  - In recent years, graphyne was found to be the only 2D carbon material that has
      both sp and sp2 hybridization. It has received significant attention because of
      its great potential in the field of optoelectronics, which arises due to its
      small band gap. In this study, the structural stability, electronic structure,
      elasticity, thermal conductivity and optical properties of alpha, beta, gamma
      graphynes were investigated using density functional theory (DFT) systematically.
      gamma-graphyne has the largest negative cohesive energy and thus the most stable
      structure, while the beta-graphyne comes 2nd. Both beta and gamma-graphynes have
      sp-sp, sp-sp2 and sp2-sp2 hybridization bonds, of which gamma-graphyne has
      shorter bond lengths and thus larger Young's modulus. Due to the difference in
      acetylenic bond in the structure cell, the effect of strain on the electronic
      structure varies between graphynes: alpha-graphyne has no band gap and is
      insensitive to strain; beta-graphyne's band gap has a sharp up-turn at 10%
      strain, while gamma-graphyne's band gap goes up linearly with the strain. All the
      three graphynes exhibit large free carrier concentration and these free carriers
      have small effective mass, and both free carrier absorption and intrinsic
      absorption are found in the light absorption. Based on the effect of strain,
      optical properties of three structures are also analyzed. It is found that the
      strain has significant impacts on their optical properties. In summary, band gap,
      thermal conductivity, elasticity and optical properties of graphyne could all be
      tailored with adjustment on the amount of acetylenic bonds in the structure cell.

PMID- 29370071
TI  - Characteristics of Pediatric Antimicrobial Stewardship Programs: Current Status
      of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS)
      Collaborative.
AB  - In response to the growing epidemic of antibiotic-resistant bacterial infections,
      antimicrobial stewardship programs (ASP) have been rapidly implemented in the
      United States (US). This study examines the prevalence of the Centers for Disease
      Control and Prevention's (CDC) seven core elements of a successful ASP within a
      large subset of US Children's Hospitals. In 2016, a survey was conducted of 52
      pediatric hospitals assessing the presence of the seven core elements: leadership
      commitment, accountability, drug expertise, action, tracking, reporting, and
      education. Forty-nine hospitals (94%) had established ASPs and 41 hospitals (79%)
      included all seven core elements. Physician accountability (87%) and a dedicated
      ASP pharmacist or drug expert (88%) were present in the vast majority of
      hospitals. However, substantial variability existed in the financial support
      allotted to these positions. This variability did not predict program actions,
      tracking, reporting, and education. When compared with previous surveys, these
      results document a dramatic increase in the prevalence and resources of pediatric
      stewardship programs, although continued expansion is warranted. Further research
      is required to understand the feasibility of various core stewardship activities
      and the impact on patient outcomes in the setting of finite resources.

PMID- 29370072
TI  - Mitochondrial BK Channel Openers CGS7181 and CGS7184 Exhibit Cytotoxic
      Properties.
AB  - Potassium channel openers (KCOs) have been shown to play a role in cytoprotection
      through the activation of mitochondrial potassium channels. Recently, in several
      reports, a number of data has been described as off-target actions for KCOs. In
      the present study, we investigated the effects of BKCa channel openers CGS7181,
      CGS7184, NS1619, and NS004 in neuronal cells. For the purpose of this research,
      we used a rat brain, the mouse hippocampal HT22 cells, and the human astrocytoma
      U-87 MG cell line. We showed that CGS7184 activated the mitochondrial BKCa
      (mitoBKCa) channel in single-channel recordings performed on astrocytoma
      mitoplasts. Moreover, when applied to the rat brain homogenate or isolated rat
      brain mitochondria, CGS7184 increased the oxygen consumption rate, and can thus
      be considered a potentially cytoprotective agent. However, experiments on intact
      neuronal HT22 cells revealed that both CGS7181 and CGS7184 induced HT22 cell
      death in a concentration- and time-dependent manner. By contrast, we did not
      observe cell death when NS1619 or NS004 was applied. CGS7184 toxicity was not
      abolished by BKCa channel inhibitors, suggesting that the observed effects were
      independent of a BKCa-type channel activity. CGS7184 treatment resulted in an
      increase of cytoplasmic Ca2+ concentration that likely involved efflux from
      internal calcium stores and the activation of calpains (calcium-dependent
      proteases). The cytotoxic effect of the channel opener was partially reversed by
      a calpain inhibitor. Our data show that KCOs under study not only activate
      mitoBKCa channels from brain tissue, but also induce cell death when used in
      cellular models.

PMID- 29370073
TI  - The Effects of Varying Degree of MWCNT Carboxylation on Bioactivity in Various In
      Vivo and In Vitro Exposure Models.
AB  - Functionalization has been shown to alter toxicity of multi-walled carbon
      nanotube (MWCNT) in several studies. This study varied the degree of
      functionalization (viz., amount of MWCNT surface carboxylation) to define the
      relationship between the extent of carboxylation and effects in a variety of in
      vitro cell models and short-term ex vivo/in vivo particle exposures. Studies with
      vitamin D3 plus phorbol ester transformed THP-1 macrophages demonstrated that
      functionalization, regardless of amount, corresponded with profoundly decreased
      NLRP3 inflammasome activation. However, all MWCNT variants were slightly toxic in
      this model. Alternatively, studies with A549 epithelial cells showed some varied
      effects. For example, IL-33 and TNF-alpha release were related to varying amounts
      of functionalization. For in vivo particle exposures, autophagy of alveolar
      macrophages, measured using green fluorescent protein (GFP)- fused-LC3 transgenic
      mice, increased for all MWCNT tested three days after exposure, but, by Day 7,
      autophagy was clearly dependent on the amount of carboxylation. The instilled
      source MWCNT continued to produce cellular injury in alveolar macrophages over
      seven days. In contrast, the more functionalized MWCNT initially showed similar
      effects, but reduced over time. Dark-field imaging showed the more functionalized
      MWCNTs were distributed more uniformly throughout the lung and not isolated to
      macrophages. Taken together, the results indicated that in vitro and in vivo
      bioactivity of MWCNT decreased with increased carboxylation. Functionalization by
      carboxylation eliminated the bioactive potential of the MWCNT in the exposure
      models tested. The observation that maximally functionalized MWCNT distribute
      more freely throughout the lung with the absence of cellular damage, and extended
      deposition, may establish a practical use for these particles as a safer
      alternative for unmodified MWCNT.

PMID- 29370074
TI  - Odor Communication and Mate Choice in Rodents.
AB  - This paper details how chemical communication is affected by ecological
      challenges such as finding mates. I list several conditions that affect the
      decision to attract mates, the decision to respond to the signals of potential
      mates and how the response depends on context. These mate-choice decisions and
      their outcomes will depend on the life history constraints placed on individuals
      such as their fecundity, sex, lifespan, opportunities to mate in the future and
      age at senescence. Consequently, the sender's decision to scent mark or self
      groom as well as the receiver's choice of response represents a tradeoff between
      the current costs of the participant's own survival and future reproduction
      against that of reproducing now. The decision to scent nark and the response to
      the scent mark of opposite-sex conspecifics should maximize the fitness of the
      participants in that context.

PMID- 29370077
TI  - p53 Gene (NY-CO-13) Levels in Patients with Chronic Myeloid Leukemia: The Role of
      Imatinib and Nilotinib.
AB  - : The p53 gene is also known as tumor suppressor p53. The main functions of the
      p53 gene are an anticancer effect and cellular genomic stability via various
      pathways including activation of DNA repair, induction of apoptosis, and
      arresting of cell growth at the G1/S phase. Normally, the p53 gene is inactivated
      by mouse double minute 2 proteins (mdm2), but it is activated in chronic myeloid
      leukemia (CML). Tyrosine kinase inhibitors are effective chemotherapeutic agents
      in the management of CML. The purpose of the present study was to evaluate the
      differential effect of imatinib and nilotinib on p53 gene serum levels in
      patients with CML. A total number of 60 patients with chronic myeloid leukemia
      with ages ranging from 47 to 59 years were recruited from the Iraqi Hematology
      Center. They started with tyrosine kinase inhibitors as first-line chemotherapy.
      They were divided into two groups-Group A, 29 patients treated with imatinib and
      Group B, 31 patients treated with nilotinib-and compared with 28 healthy subjects
      for evaluation p53 serum levels regarding the selective effect of either imatinib
      or nilotinib. There were significantly (p < 0.01) high p53 gene serum levels in
      patients with CML (2.135 +/- 1.44 ng/mL) compared to the control (0.142 +/- 0.11
      ng/mL). Patients with CML that were treated with either imatinib or nilotinib
      showed insignificant differences in most of the hematological profile (p > 0.05)
      whereas, p53 serum levels were high (3.22 +/- 1.99 ng/mL) in nilotinib-treated
      patients and relatively low (1.18 +/- 0.19 ng/mL) in imatinib-treated patients (p
      = 0.0001). CONCLUSIONS: Nilotinib is more effective than imatinib in raising p53
      serum levels in patients with chronic myeloid leukemia.

PMID- 29370075
TI  - Another Round of "Clue" to Uncover the Mystery of Complex Traits.
AB  - A plethora of genetic association analyses have identified several genetic risk
      loci. Technological and statistical advancements have now led to the
      identification of not only common genetic variants, but also low-frequency
      variants, structural variants, and environmental factors, as well as multi-omics
      variations that affect the phenotypic variance of complex traits in a population,
      thus referred to as complex trait architecture. The concept of heritability, or
      the proportion of phenotypic variance due to genetic inheritance, has been
      studied for several decades, but its application is mainly in addressing the
      narrow sense heritability (or additive genetic component) from Genome-Wide
      Association Studies (GWAS). In this commentary, we reflect on our perspective on
      the complexity of understanding heritability for human traits in comparison to
      model organisms, highlighting another round of clues beyond GWAS and an
      alternative approach, investigating these clues comprehensively to help in
      elucidating the genetic architecture of complex traits.

PMID- 29370076
TI  - The Anti-Stress Effect of Mentha arvensis in Immobilized Rats.
AB  - Stress can lead to inflammation, accelerated aging, and some chronic diseases
      condition. Mentha arvensis (MA) is a traditional medicine having antioxidant and
      anti-inflammatory activities. The present study investigated the anti-stress role
      of MA and fermented MA (FMA) extract in immobilized rats. We studied the
      lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells and rats were
      immobilized for 2 h per day for 14 days using a restraining cage. MA (100 mg/kg)
      and FMA (100 mg/kg) were orally administered to rats 1 h prior to immobilization.
      Using high-performance liquid chromatography (HPLC) analysis, we determined the
      rosmarinic acid content of MA and FMA. The generation of malondialdehyde (MDA)
      and nitric oxide (NO) in RAW 246.7 cells were suppressed by both MA and FMA. In
      rats, MA and FMA notably improved the body weight, daily food intake, and
      duodenum histology. MDA and NO level were gradually decreased by MA and FMA
      treatment. MA and FMA significantly controlled the stress-related hormones by
      decreasing corticosterone and beta-endorphin and increasing serotonin level.
      Moreover, protein expression levels of mitogen activated protein kinases (MAPK)
      and cyclooxygenase-2 (COX-2) were markedly downregulated by MA and FMA. Taken
      together, MA and FMA could ameliorate immobilized-stress by reducing oxidative
      stress, regulating stress-related hormones, and MAPK/COX-2 signaling pathways in
      rats. Particularly, FMA has shown greater anti-stress activities than MA.

PMID- 29370078
TI  - Present Status and Future Challenges of New Therapeutic Targets in Preclinical
      Models of Stroke in Aged Animals with/without Comorbidities.
AB  - The aging process, comorbidities, and age-associated diseases are closely
      dependent on each other. Cerebral ischemia impacts a wide range of systems in an
      age-dependent manner. However, the aging process has many facets which are
      influenced by the genetic background and epigenetic or environmental factors,
      which can explain why some people age differently than others. Therefore, there
      is an urgent need to identify age-related changes in body functions or structures
      that increase the risk for stroke and which are associated with a poor outcome.
      Multimodal imaging, electrophysiology, cell biology, proteomics, and
      transcriptomics, offer a useful approach to link structural and functional
      changes in the aging brain, with or without comorbidities, to post-stroke
      rehabilitation. This can help us to improve our knowledge about senescence
      firstly, and in this context, aids in elucidating the pathophysiology of age
      related diseases that allows us to develop therapeutic strategies or prevent
      diseases. These processes, including potential therapeutical interventions, need
      to be studied first in relevant preclinical models using aged animals, with and
      without comorbidities. Therefore, preclinical research on ischemic stroke should
      consider age as the most important risk factor for cerebral ischemia.
      Furthermore, the identification of effective therapeutic strategies, corroborated
      with successful translational studies, will have a dramatic impact on the lives
      of millions of people with cerebrovascular diseases.

PMID- 29370079
TI  - The Asbestos Ban in Korea from a Grassroots Perspective: Why Did It Occur?
AB  - In 2009, asbestos was finally banned in Korea, about 70 years after the first
      opening of asbestos mines under Japanese control. After having presented the
      history of asbestos industry, together with its regulations and health effects
      over time, we constructed narrative analyses of how the asbestos issue under the
      prevailing risk system was managed by whom and for what purpose, to provide
      context for the change. We could identify five different phases: laissez-faire,
      politico-technical, economic-managerial, health-oriented cultural, and human
      rights-based post-cultural risk systems. The changes leading to the asbestos ban
      evolved over different phases, and each phase change was necessary to reach the
      final ban, in that, without resolving the previous issues by examining different
      categories of potential alternatives, either the final ban was not possible or,
      even if instituted, could not be sustained. An asbestos ban could be introduced
      when all the alternatives to these issues, including legitimate political
      windows, economic rationalizations, health risk protections, and human rights
      sensitivities, were available. We think the alternatives that we had were not in
      perfect shape, but in more or less loosely connected forms, and hence we had to
      know how to build solidarities between different stakeholders to compensate for
      the imperfections.

PMID- 29370080
TI  - Controversies and Advances in Gestational Diabetes-An Update in the Era of
      Continuous Glucose Monitoring.
AB  - Diabetes in pregnancy, both preexisting type 1 or type 2 and gestational
      diabetes, is a highly prevalent condition, which has a great impact on maternal
      and fetal health, with short and long-term implications. Gestational Diabetes
      Mellitus (GDM) is a condition triggered by metabolic adaptation, which occurs
      during the second half of pregnancy. There is still a lot of controversy about
      GDM, from classification and diagnosis to treatment. Recently, there have been
      some advances in the field as well as recommendations from international
      societies, such as how to distinguish previous diabetes, even if first recognized
      during pregnancy, and newer diagnostic criteria, based on pregnancy outcomes,
      instead of maternal risk of future diabetes. These new recommendations will lead
      to a higher prevalence of GDM, and important issues are yet to be resolved, such
      as the cost-utility of this increase in diagnoses as well as the determinants for
      poor outcomes. The aim of this review is to discuss the advances in diagnosis and
      classification of GDM, as well as their implications in the field, the issue of
      hyperglycemia in early pregnancy and the role of hemoglobin A1c (HbA1c) during
      pregnancy. We have looked into the determinants of the poor outcomes predicted by
      the diagnosis by way of oral glucose tolerance tests, highlighting the relevance
      of continuous glucose monitoring tools, as well as other possible pathogenetic
      factors related to poor pregnancy outcomes.

PMID- 29370081
TI  - What Constitutes Traditional and Modern Eating? The Case of Japan.
AB  - Traditional Japanese dietary culture might be a factor contributing to the high
      life expectancy in Japan. As little is known about what constitutes traditional
      and modern eating in Japan, the aims of the current study were to (1)
      comprehensively compile and systematize the various facets of traditional and
      modern eating; and (2) investigate whether these facets also apply to traditional
      and modern eating in Japan. In Study 1, an extensive international literature
      review was performed. Forty-five facets of traditional and modern eating were
      compiled and systematized into the dimensions of what and how people eat, and
      into eleven separate subdimensions. In Study 2, 340 adults from Japan answered a
      questionnaire. Results showed that traditional and modern eating in Japan is
      reflected in both what and how people eat. Within these two dimensions, ten
      subdimensions were found: the ingredients, processing, temporal origin, spatial
      origin, and variety of consumed foods, as well as temporal, spatial, and social
      aspects, appreciation, and concerns when eating. This study provides a broad
      compilation of facets of traditional and modern eating in Japan. Future research
      should investigate how these facets are related to life expectancy and health.

PMID- 29370082
TI  - Monitoring of Bridges by a Laser Pointer: Dynamic Measurement of Support
      Rotations and Elastic Line Displacements: Methodology and First Test.
AB  - Deck inclination and vertical displacements are among the most important
      technical parameters to evaluate the health status of a bridge and to verify its
      bearing capacity. Several methods, both conventional and innovative, are used for
      structural rotations and displacement monitoring; however, none of these allow,
      at the same time, precision, automation, static and dynamic monitoring without
      using high cost instrumentation. The proposed system uses a common laser pointer
      and image processing. The elastic line inclination is measured by analyzing the
      single frames of an HD video of the laser beam imprint projected on a flat
      target. For the image processing, a code was developed in Matlab(r) that provides
      instantaneous rotation and displacement of a bridge, charged by a mobile load. An
      important feature is the synchronization of the load positioning, obtained by a
      GNSS receiver or by a video. After the calibration procedures, a test was carried
      out during the movements of a heavy truck maneuvering on a bridge. Data
      acquisition synchronization allowed us to relate the position of the truck on the
      deck to inclination and displacements. The inclination of the elastic line at the
      support was obtained with a precision of 0.01 mrad. The results demonstrate the
      suitability of the method for dynamic load tests, and the control and monitoring
      of bridges.

PMID- 29370083
TI  - Fungal Screening on Olive Oil for Extracellular Triacylglycerol Lipases:
      Selection of a Trichoderma harzianum Strain and Genome Wide Search for the Genes.
AB  - A lipolytic screening with fungal strains isolated from lignocellulosic waste
      collected in banana plantation dumps was carried out. A Trichoderma harzianum
      strain (B13-1) showed good extracellular lipolytic activity (205 UmL-1).
      Subsequently, functional screening of the lipolytic activity on Rhodamine B
      enriched with olive oil as the only carbon source was performed. The successful
      growth of the strain allows us to suggest that a true lipase is responsible for
      the lipolytic activity in the B13-1 strain. In order to identify the gene(s)
      encoding the protein responsible for the lipolytic activity, in silico
      identification and characterization of triacylglycerol lipases from T. harzianum
      is reported for the first time. A survey in the genome of this fungus retrieved
      50 lipases; however, bioinformatic analyses and putative functional descriptions
      in different databases allowed us to choose seven lipases as candidates.
      Suitability of the bioinformatic screening to select the candidates was confirmed
      by reverse transcription polymerase chain reaction (RT-PCR). The gene codifying
      526309 was expressed when the fungus grew in a medium with olive oil as carbon
      source. This protein shares homology with commercial lipases, making it a
      candidate for further applications. The success in identifying a lipase gene
      inducible with olive oil and the suitability of the functional screening and
      bioinformatic survey carried out herein, support the premise that the strategy
      can be used in other microorganisms with sequenced genomes to search for true
      lipases, or other enzymes belonging to large protein families.

PMID- 29370084
TI  - A Systematic Study on the Structural and Optical Properties of Vertically Aligned
      Zinc Oxide Nanorods Grown by High Pressure Assisted Pulsed Laser Deposition
      Technique.
AB  - In this study, we synthesize high quality vertically aligned ZnO (VAZO) nanorods
      on silicon, sapphire, and indium tin oxide (ITO) substrates by using pulsed laser
      deposition (PLD) technique at high growth pressure (0.3 Torr). Systematic changes
      in structural and optical properties of VAZO nanorods are studied by varying the
      substrate temperature (500-600  degrees C) and number of pulsed laser shots
      during the deposition. ZnO nanoparticles deposited at high pressure act as
      nucleation sites, eliminating requirement of catalyst to fabricate VAZO nanorods.
      Two sharp ZnO peaks with high intensity correspond to the (0002) and (0004)
      planes in X-ray diffraction pattern confirm the growth of ZnO nanorods, oriented
      along the c-axis. Scanning Electron Microscopy (SEM) images indicate a regular
      arrangement of vertically aligned hexagonal closed pack nano-structures of ZnO.
      The vertical alignment of ZnO nanorods is also supported by the presence of E2
      (high) and A1 (LO) modes in Raman spectra. We can tune the diameter of VAZO
      nanorods by changing growth temperature and annealing environments.
      Photoluminescence spectroscopy illustrates reduction in defect level peak
      intensities with increase in diameter of VAZO nanorods. This study signifies that
      high pressure PLD technique can be used more efficiently for controlled and
      efficient growth of VAZO nanorods on different substrates.

PMID- 29370085
TI  - A Prospective Evaluation of Duplex Ultrasound for Thoracic Outlet Syndrome in
      High-Performance Musicians Playing Bowed String Instruments
AB  - Thoracic outlet syndrome (TOS) is a neurovascular condition involving the upper
      extremity, which is known to occur in individuals who perform chronic repetitive
      upper extremity activities. We prospectively evaluate the incidence of TOS in
      high-performance musicians who played bowed string musicians. Sixty-four high
      performance string instrument musicians from orchestras and professional musical
      bands were included in the study. Fifty-two healthy volunteers formed an age
      matched control group. Bilateral upper extremity duplex scanning for subclavian
      vessel compression was performed in all subjects. Provocative maneuvers including
      Elevated Arm Stress Test (EAST) and Upper Limb Tension Test (ULTT) were
      performed. Abnormal ultrasound finding is defined by greater than 50% subclavian
      vessel compression with arm abduction, diminished venous waveforms, or arterial
      photoplethysmography (PPG) tracing with arm abduction. Bowed string instruments
      performed by musicians in our study included violin (41%), viola (33%), and cello
      (27%). Positive EAST or ULTT test in the musician group and control group were
      44%, and 3%, respectively (p = 0.03). Abnormal ultrasound scan with vascular
      compression was detected in 69% of musicians, in contrast to 15% of control
      subjects (p = 0.03). TOS is a common phenomenon among high-performance bowed
      string instrumentalists. Musicians who perform bowed string instruments should be
      aware of this condition and its associated musculoskeletal symptoms.

PMID- 29370086
TI  - Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across
      Membrane Barrier in T-Cell Lymphoma.
AB  - Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold
      the promise to be utilized as desired materials for encapsulating molecules which
      demonstrate wide promise in drug delivery. We evaluate the possibility to
      encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor
      that is currently in phase I/II clinical trials for advanced solid tumors, from
      the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce
      to administer high doses leading to toxicity; to overcome these problems, here we
      proposed a strategy to enhance its intracellular penetration and its biological
      activity. Pristine CaCO3 NCs biocompatibility, cell interactions and
      internalization in in vitro experiments on T-cell lymphoma line, were studied.
      Confocal microscopy was used to monitor NCs-cell interactions and cellular
      uptake. We have further investigated the interaction nature and release mechanism
      of drug loaded/released within/from the NCs using an alternative approach based
      on liquid chromatography coupled to mass spectrometry. Our approach provides a
      good loading efficiency, therefore this drug delivery system was validated for
      biological activity in T-cell lymphoma: the anti-proliferative test and western
      blot results are very interesting because the proposed nano-formulation has an
      efficiency higher than free drug at the same nominal concentration.

PMID- 29370087
TI  - A Novel Bromophenol Derivative BOS-102 Induces Cell Cycle Arrest and Apoptosis in
      Human A549 Lung Cancer Cells via ROS-Mediated PI3K/Akt and the MAPK Signaling
      Pathway.
AB  - Bromophenol is a type of natural marine product. It has excellent biological
      activities, especially anticancer activities. In our study of searching for
      potent anticancer drugs, a novel bromophenol derivative containing indolin-2-one
      moiety, 3-(4-(3-([1,4'-bipiperidin]-1'-yl)propoxy)-3-bromo-5-methoxybenzylidene)
      N-(4-bromophenyl)-2-oxoindoline-5-sulfonamide (BOS-102) was synthesized, which
      showed excellent anticancer activities on human lung cancer cell lines. A study
      of the mechanisms indicated that BOS-102 could significantly block cell
      proliferation in human A549 lung cancer cells and effectively induce G0/G1 cell
      cycle arrest via targeting cyclin D1 and cyclin-dependent kinase 4 (CDK4). BOS
      102 could also induce apoptosis, including activating caspase-3 and poly (ADP
      ribose) polymerase (PARP), increasing the Bax/Bcl-2 ratio, enhancing reactive
      oxygen species (ROS) generation, decreasing mitochondrial membrane potential
      (MMP, DeltaPsim), and leading cytochrome c release from mitochondria. Further
      research revealed that BOS-102 deactivated the PI3K/Akt pathway and activated the
      mitogen-activated protein kinase (MAPK) signaling pathway resulting in apoptosis
      and cell cycle arrest, which indicated that BOS-102 has the potential to develop
      into an anticancer drug.

PMID- 29370088
TI  - The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer
      Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage.
AB  - Radiation therapy is commonly used for prostate cancer treatment; however, normal
      tissues can be damaged from the reactive oxygen species (ROS) produced by
      radiation. In separate reports, we and others have shown that manganese
      porphyrins (MnPs), ROS scavengers, protect normal cells from radiation-induced
      damage but inhibit prostate cancer cell growth. However, there have been no
      studies demonstrating that MnPs protect normal tissues, while inhibiting tumor
      growth in the same model. LNCaP or PC3 cells were orthotopically implanted into
      athymic mice and treated with radiation (2 Gy, for 5 consecutive days) in the
      presence or absence of MnPs. With radiation, MnPs enhanced overall life
      expectancy and significantly decreased the average tumor volume, as compared to
      the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but
      reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor
      in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or
      antioxidants depending on the level of oxidative stress inside the treated cell.
      We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal
      cells and tissues the MnPs act as antioxidants. For the first time, in the same
      in vivo model, this study reveals that MnPs enhance the tumoricidal effect of
      radiation and reduce oxidative damage to normal prostate tissue adjacent to the
      prostate tumor in the presence of radiation. This study suggests that MnPs are
      effective radio-protectors for radiation-mediated prostate cancer treatment.

PMID- 29370089
TI  - Raman Imaging of Plant Cell Walls in Sections of Cucumis sativus.
AB  - Raman microspectra combine information on chemical composition of plant tissues
      with spatial information. The contributions from the building blocks of the cell
      walls in the Raman spectra of plant tissues can vary in the microscopic sub
      structures of the tissue. Here, we discuss the analysis of 55 Raman maps of root,
      stem, and leaf tissues of Cucumis sativus, using different spectral contributions
      from cellulose and lignin in both univariate and multivariate imaging methods.
      Imaging based on hierarchical cluster analysis (HCA) and principal component
      analysis (PCA) indicates different substructures in the xylem cell walls of the
      different tissues. Using specific signals from the cell wall spectra, analysis of
      the whole set of different tissue sections based on the Raman images reveals
      differences in xylem tissue morphology. Due to the specifics of excitation of the
      Raman spectra in the visible wavelength range (532 nm), which is, e.g., in
      resonance with carotenoid species, effects of photobleaching and the possibility
      of exploiting depletion difference spectra for molecular characterization in
      Raman imaging of plants are discussed. The reported results provide both,
      specific information on the molecular composition of cucumber tissue Raman
      spectra, and general directions for future imaging studies in plant tissues.

PMID- 29370090
TI  - Genotyping by Sequencing Highlights a Polygenic Resistance to Ralstonia
      pseudosolanacearum in Eggplant (Solanum melongena L.).
AB  - Eggplant cultivation is limited by numerous diseases, including the devastating
      bacterial wilt (BW) caused by the Ralstonia solanacearum species complex (RSSC).
      Within the RSSC, Ralstonia pseudosolanacearum (including phylotypes I and III)
      causes severe damage to all solanaceous crops, including eggplant. Therefore, the
      creation of cultivars resistant to R. pseudosolanacearum strains is a major goal
      for breeders. An intraspecific eggplant population, segregating for resistance,
      was created from the cross between the susceptible MM738 and the resistant EG203
      lines. The population of 123 doubled haploid lines was challenged with two
      strains belonging to phylotypes I (PSS4) and III (R3598), which both bypass the
      published EBWR9 BW-resistance quantitative trait locus (QTL). Ten and three QTLs
      of resistance to PSS4 and to R3598, respectively, were detected and mapped. All
      were strongly influenced by environmental conditions. The most stable QTLs were
      found on chromosomes 3 and 6. Given their estimated physical position, these
      newly detected QTLs are putatively syntenic with BW-resistance QTLs in tomato. In
      particular, the QTLs' position on chromosome 6 overlaps with that of the major
      broad-spectrum tomato resistance QTL Bwr-6. The present study is a first step
      towards understanding the complex polygenic system, which underlies the high
      level of BW resistance of the EG203 line.

PMID- 29370092
TI  - Low Power Operation of Temperature-Modulated Metal Oxide Semiconductor Gas
      Sensors.
AB  - Mobile applications based on gas sensing present new opportunities for low-cost
      air quality monitoring, safety, and healthcare. Metal oxide semiconductor (MOX)
      gas sensors represent the most prominent technology for integration into portable
      devices, such as smartphones and wearables. Traditionally, MOX sensors have been
      continuously powered to increase the stability of the sensing layer. However,
      continuous power is not feasible in many battery-operated applications due to
      power consumption limitations or the intended intermittent device operation. This
      work benchmarks two low-power, duty-cycling, and on-demand modes against the
      continuous power one. The duty-cycling mode periodically turns the sensors on and
      off and represents a trade-off between power consumption and stability. On-demand
      operation achieves the lowest power consumption by powering the sensors only
      while taking a measurement. Twelve thermally modulated SB-500-12 (FIS Inc.
      Jacksonville, FL, USA) sensors were exposed to low concentrations of carbon
      monoxide (0-9 ppm) with environmental conditions, such as ambient humidity (15
      75% relative humidity) and temperature (21-27  degrees C), varying within the
      indicated ranges. Partial Least Squares (PLS) models were built using calibration
      data, and the prediction error in external validation samples was evaluated
      during the two weeks following calibration. We found that on-demand operation
      produced a deformation of the sensor conductance patterns, which led to an
      increase in the prediction error by almost a factor of 5 as compared to
      continuous operation (2.2 versus 0.45 ppm). Applying a 10% duty-cycling operation
      of 10-min periods reduced this prediction error to a factor of 2 (0.9 versus 0.45
      ppm). The proposed duty-cycling powering scheme saved up to 90% energy as
      compared to the continuous operating mode. This low-power mode may be
      advantageous for applications that do not require continuous and periodic
      measurements, and which can tolerate slightly higher prediction errors.

PMID- 29370091
TI  - Effects of Glutamine and Alanine Supplementation on Central Fatigue Markers in
      Rats Submitted to Resistance Training.
AB  - Recent evidence suggests that increased brain serotonin synthesis impairs
      performance in high-intensity intermittent exercise and specific amino acids may
      modulate this condition, delaying fatigue. This study investigated the effects of
      glutamine and alanine supplementation on central fatigue markers in rats
      submitted to resistance training (RT). Wistar rats were distributed in: sedentary
      (SED), trained (CON), trained and supplemented with alanine (ALA), glutamine and
      alanine in their free form (G + A), or as dipeptide (DIP). Trained groups
      underwent a ladder-climbing exercise for eight weeks, with progressive loads. In
      the last 21 days, supplementations were offered in water with a 4% concentration.
      Albeit without statistically significance difference, RT decreased liver
      glycogen, and enhanced the concentrations of plasma glucose, free fatty acids
      (FFA), hypothalamic serotonin, and ammonia in muscle and the liver. Amino acids
      affected fatigue parameters depending on the supplementation form. G + A
      prevented the muscle ammonia increase by RT, whereas ALA and DIP augmented
      ammonia and glycogen concentrations in muscle. DIP also increased liver ammonia.
      ALA and G + A reduced plasma FFA, whereas DIP increased this parameter, free
      tryptophan/total tryptophan ratio, hypothalamic serotonin, and the
      serotonin/dopamine ratio. The supplementations did not affect physical
      performance. In conclusion, glutamine and alanine may improve or impair central
      fatigue markers depending on their supplementation form.

PMID- 29370094
TI  - Undertaking a Collaborative Rapid Realist Review to Investigate What Works in the
      Successful Implementation of a Frail Older Person's Pathway.
AB  - We addressed the research question "what factors enable the successful
      development and implementation of a frail older person's pathway within the acute
      setting". A rapid realist review (RRR) was conducted by adopting the RAMESES
      standards. We began with a sample of 232 articles via database searches
      supplemented with 94 additional records including inputs from a twitter chat and
      a hospital site visit. Our final sample consisted of 18 documents. Following
      review and consensus by an expert panel we identified a conceptual model of
      context-mechanism-(resources)-outcomes. There was overall agreement frailty
      should be identified at the front door of the acute hospital. Significant
      challenges identified related to organisational boundaries both within the acute
      setting and externally, the need to shift outcomes to patient orientated ones, to
      support staff to sustain the pathway by providing ongoing education and by
      providing role clarity. RRRs can support research such as the systematic approach
      to improving care for frail older adults (SAFE) study by producing accounts of
      what works based on a wide range of sources and innovative engagement with
      stakeholders. It is evident from our provisional model that numerous factors need
      to combine and interact to enable and sustain a successful frail older person's
      pathway.

PMID- 29370095
TI  - Innovative Clinical Perspectives for CIK Cells in Cancer Patients.
AB  - Cytokine-induced killer (CIK) cells are T lymphocytes that have acquired, in
      vitro, following extensive manipulation by Interferon gamma (IFN-gamma), OKT3 and
      Interleukin 2 (IL-2) addition, the expression of several Natural Killer (NK) cell
      surface markers. CIK cells have a dual "nature", due to the presence of
      functional TCR as well as NK molecules, even if the antitumoral activity can be
      traced back only to the NK-like structures (DNAM-1, NKG2D, NKp30 and CD56). In
      addition to antineoplastic activity in vitro and in several in-vivo models, CIK
      cells show very limited, if any, GvHD toxicity as well as a strong intratumoral
      homing. For all such reasons, CIK cells have been proposed and tested in many
      clinical trials in cancer patients both in autologous and allogeneic
      combinations, up to haploidentical mismatching. Indeed, genetic modification of
      CIK cells as well as the possibility of combining them with specific monoclonal
      antibodies will further expand the possibility of their clinical utilization.

PMID- 29370096
TI  - Accurate Estimation of the Standard Binding Free Energy of Netropsin with DNA.
AB  - DNA is the target of chemical compounds (drugs, pollutants, photosensitizers,
      etc.), which bind through non-covalent interactions. Depending on their structure
      and their chemical properties, DNA binders can associate to the minor or to the
      major groove of double-stranded DNA. They can also intercalate between two
      adjacent base pairs, or even replace one or two base pairs within the DNA double
      helix. The subsequent biological effects are strongly dependent on the
      architecture of the binding motif. Discriminating between the different binding
      patterns is of paramount importance to predict and rationalize the effect of a
      given compound on DNA. The structural characterization of DNA complexes remains,
      however, cumbersome at the experimental level. In this contribution, we employed
      all-atom molecular dynamics simulations to determine the standard binding free
      energy of DNA with netropsin, a well-characterized antiviral and antimicrobial
      drug, which associates to the minor groove of double-stranded DNA. To overcome
      the sampling limitations of classical molecular dynamics simulations, which
      cannot capture the large change in configurational entropy that accompanies
      binding, we resort to a series of potentials of mean force calculations involving
      a set of geometrical restraints acting on collective variables.

PMID- 29370098
TI  - Analysis and Assessment of Exposure to Selected Phthalates Found in Children's
      Toys in Christchurch, New Zealand.
AB  - Internationally several phthalates are subject to regulatory control regarding
      maximum allowable concentrations in children's toys. Such regulation is not in
      place in New Zealand. Phthalates have been associated with developmental toxicity
      and endocrine disruption. We determined the concentration of seven phthalates in
      children's toys purchased in Christchurch, New Zealand. These results provided
      data for an exposure assessment deriving Hazard Indices (HI) for oral and dermal
      exposure routes in children, based on the concentration of mixtures of phthalates
      shown by the EU to produce either reproductive/developmental or hepatotoxic
      effects. Of the 49 toys analyzed, 65% contained at least one phthalate at a
      concentration of >0.1% by mass; and 35% contained multiple-phthalates at
      individual concentrations of >0.1%. A HI of 3.4 was derived for the combined
      exposures to the four phthalates associated with reproductive and developmental
      effects. A HI of 0.3 was derived for the group of phthalates associated with
      hepatotoxic effects. Five phthalates were detected at levels exceeding the EU
      regulatory limit of 0.1% by mass. Risk assessment calculations indicate that,
      using realistic exposure scenarios, the worst-case combined exposure to
      phthalates associated with developmental toxicity exceeded a HI of 1 so may cause
      adverse developmental effects.

PMID- 29370099
TI  - Fabrications and Performance of Wireless LC Pressure Sensors through LTCC
      Technology.
AB  - This paper presents a kind of passive wireless pressure sensor comprised of a
      planar spiral inductor and a cavity parallel plate capacitor fabricated through
      low-temperature co-fired ceramic (LTCC) technology. The LTCC material with a low
      Young's modulus of ~65 GPa prepared by our laboratory was used to obtain high
      sensitivity. A three-step lamination process was applied to construct a high
      quality cavity structure without using any sacrificial materials. The effects of
      the thickness of the sensing membranes on the sensitivity and detection range of
      the pressure sensors were investigated. The sensor with a 148 MUm sensing
      membrane showed the highest sensitivity of 3.76 kHz/kPa, and the sensor with a
      432 MUm sensing membrane presented a high detection limit of 2660 kPa. The
      tunable sensitivity and detection limit of the wireless pressure sensors can meet
      the requirements of different scenes.

PMID- 29370097
TI  - Alternative Splicing of Alpha- and Beta-Synuclein Genes Plays Differential Roles
      in Synucleinopathies.
AB  - The synuclein family is composed of three members, two of which, alpha- and beta
      synuclein, play a major role in the development of synucleinopathies, including
      Parkinson's disease (PD) as most important movement disorder, dementia with Lewy
      bodies (DLB) as the second most frequent cause of dementia after Alzheimer's
      disease and multiple system atrophy. Whereas abnormal oligomerization and
      fibrillation of alpha-synuclein are now well recognized as initial steps in the
      development of synucleinopathies, beta-synuclein is thought to be a natural alpha
      synuclein anti-aggregant. alpha-synuclein is encoded by the SNCA gene, and beta
      synuclein by SNCB. Both genes are homologous and undergo complex splicing events.
      On one hand, in-frame splicing of coding exons gives rise to at least three
      shorter transcripts, and the functional properties of the corresponding protein
      isoforms are different. Another type of alternative splicing is the alternative
      inclusion of at least four initial exons in the case of SNCA, and two in the case
      of SNCB. Finally, different lengths of 3' untranslated regions have been also
      reported for both genes. SNCB only expresses in the brain, but some of the
      numerous SNCA transcripts are also brain-specific. With the present article, we
      aim to provide a systematic review of disease related changes in the differential
      expression of the various SNCA and SNCB transcript variants in brain, blood, and
      non-neuronal tissue of synucleinopathies, but especially PD and DLB as major
      neurodegenerative disorders.

PMID- 29370100
TI  - Chemical Modification of Chitosan for Efficient Vaccine Delivery.
AB  - Chitosan, which exhibits good biocompatibility, safety, microbial degradation and
      other excellent performances, has found application in all walks of life. In the
      field of medicine, usage of chitosan for the delivery of vaccine is favored by a
      wide range of researchers. However, due to its own natural limitations, its
      application has been constrained to the beginning of study. In order to improve
      the applicability for vaccine delivery, researchers have carried out various
      chemical modifications of chitosan. This review summarizes a variety of
      modification methods and applications of chitosan and its derivatives in the
      field of vaccine delivery.

PMID- 29370101
TI  - Aging Donor-Derived Human Mesenchymal Stem Cells Exhibit Reduced Reactive Oxygen
      Species Loads and Increased Differentiation Potential Following Serial Expansion
      on a PEG-PCL Copolymer Substrate.
AB  - Human mesenchymal stem cells (hMSCs) have been widely studied for therapeutic
      development in tissue engineering and regenerative medicine. They can be
      harvested from human donors via tissue biopsies, such as bone marrow aspiration,
      and cultured to reach clinically relevant cell numbers. However, an unmet issue
      lies in the fact that the hMSC donors for regenerative therapies are more likely
      to be of advanced age. Their stem cells are not as potent compared to those of
      young donors, and continue to lose healthy, stemness-related activities when the
      hMSCs are serially passaged in tissue culture plates. Here, we have developed a
      cheap, scalable, and effective copolymer film to culture hMSCs obtained from aged
      human donors over several passages without loss of reactive oxygen species (ROS)
      handling or differentiation capacity. Assays of cell morphology, reactive oxygen
      species load, and differentiation potential demonstrate the effectiveness of
      copolymer culture on reduction in senescence-related activities of aging donor
      derived hMSCs that could hinder the therapeutic potential of autologous stem cell
      therapies.

PMID- 29370103
TI  - A Novel Loss Recovery and Tracking Scheme for Maneuvering Target in Hybrid WSNs.
AB  - Tracking a mobile target, which aims to timely monitor the invasion of specific
      target, is one of the most prominent applications in wireless sensor networks
      (WSNs). Traditional tracking methods in WSNs only based on static sensor nodes
      (SNs) have several critical problems. For example, to void the loss of mobile
      target, many SNs must be active to track the target in all possible directions,
      resulting in excessive energy consumption. Additionally, when entering coverage
      holes in the monitoring area, the mobile target may be missing and then its state
      is unknown during this period. To tackle these problems, in this paper, a few
      mobile sensor nodes (MNs) are introduced to cooperate with SNs to form a hybrid
      WSN due to their stronger abilities and less constrained energy. Then, we propose
      a valid target tracking scheme for hybrid WSNs to dynamically schedule the MNs
      and SNs. Moreover, a novel loss recovery mechanism is proposed to find the lost
      target and recover the tracking with fewer SNs awakened. Furthermore, to improve
      the robustness and accuracy of the recovery mechanism, an adaptive unscented
      Kalman filter (AUKF) algorithm is raised to dynamically adjust the process noise
      covariance. Simulation results demonstrate that our tracking scheme for
      maneuvering target in hybrid WSNs can not only track the target effectively even
      if the target is lost but also maintain an excellent accuracy and robustness with
      fewer activated nodes.

PMID- 29370104
TI  - Exploring Reaction Conditions to Improve the Magnetic Response of Cobalt-Doped
      Ferrite Nanoparticles.
AB  - With the aim of studying the influence of synthesis parameters in structural and
      magnetic properties of cobalt-doped magnetite nanoparticles, Fe3-xCoxO4 (0 < x <
      0.15) samples were synthetized by thermal decomposition method at different
      reaction times (30-120 min). The Co ferrite nanoparticles are monodisperse with
      diameters between 6 and 11 nm and morphologies depending on reaction times,
      varying from spheric, cuboctahedral, to cubic. Chemical analysis and X-ray
      diffraction were used to confirm the composition, high crystallinity, and pure
      phase structure. The investigation of the magnetic properties, both magnetization
      and electronic magnetic resonance, has led the conditions to improve the magnetic
      response of doped nanoparticles. Magnetization values of 86 emu.g-1 at room
      temperature (R.T.) have been obtained for the sample with the highest Co content
      and the highest reflux time. Magnetic characterization also displays a dependence
      of the magnetic anisotropy constant with the varying cobalt content.

PMID- 29370102
TI  - NMR-Fragment Based Virtual Screening: A Brief Overview.
AB  - Fragment-based drug discovery (FBDD) using NMR has become a central approach over
      the last twenty years for development of small molecule inhibitors against
      biological macromolecules, to control a variety of cellular processes. Yet,
      several considerations should be taken into account for obtaining a
      therapeutically relevant agent. In this review, we aim to list the considerations
      that make NMR fragment screening a successful process for yielding potent
      inhibitors. Factors that may govern the competence of NMR in fragment based drug
      discovery are discussed, as well as later steps that involve optimization of hits
      obtained by NMR-FBDD.

PMID- 29370105
TI  - Tackling Cancer Resistance by Immunotherapy: Updated Clinical Impact and Safety
      of PD-1/PD-L1 Inhibitors.
AB  - Cancer therapy has been constantly evolving with the hope of finding the most
      effective agents with the least toxic effects to eradicate tumors. Cancer
      immunotherapy is currently among the most promising options, fulfilling this hope
      in a wide range of tumors. Immunotherapy aims to activate immunity to fight
      cancer in a very specific and targeted manner; however, some abnormal immune
      reactions known as immune-related adverse events (IRAEs) might occur. Therefore,
      many researchers are aiming to define the most proper protocols for managing
      these complications without interfering with the anticancer effect. One of these
      targeted approaches is the inhibition of the interaction between the checkpoint
      protein, programmed death-receptor 1 (PD-1), and its ligand, programmed death
      ligand 1 (PD-L1), via a class of antibodies known as PD-1/PD-L1 inhibitors. These
      antibodies achieved prodigious success in a wide range of malignancies, including
      those where optimal treatment is not yet fully identified. In this review, we
      have critically explored and discussed the outcome of the latest PD-1 and PD-L1
      inhibitor studies in different malignancies compared to standard chemotherapeutic
      alternatives with a special focus on the clinical efficacy and safety. The
      approval of the clinical applications of nivolumab, pembrolizumab, atezolizumab,
      avelumab, and durvalumab in the last few years clearly highlights the hopeful
      future of PD-1/PD-L1 inhibitors for cancer patients. These promising results of
      PD-1/PD-L1 inhibitors have encouraged many ongoing preclinical and clinical
      trials to explore the extent of antitumor activity, clinical efficacy and safety
      as well as to extend their applications.

PMID- 29370106
TI  - Preliminary Results of a New Auxiliary Mechatronic Near-Field Radar System to 3D
      Mammography for Early Detection of Breast Cancer.
AB  - Accurate and early detection of breast cancer is of high importance, as it is
      directly associated with the patients' overall well-being during treatment and
      their chances of survival. Uncertainties in current breast imaging methods can
      potentially cause two main problems: (1) missing newly formed or small tumors;
      and (2) false alarms, which could be a source of stress for patients. A recent
      study at the Massachusetts General Hospital (MGH) indicates that using Digital
      Breast Tomosynthesis (DBT) can reduce the number of false alarms, when compared
      to conventional mammography. Despite the image quality enhancement DBT provides,
      the accurate detection of cancerous masses is still limited by low radiological
      contrast (about 1%) between the fibro-glandular tissue and affected tissue at X
      ray frequencies. In a lower frequency region, at microwave frequencies, the
      contrast is comparatively higher (about 10%) between the aforementioned tissues;
      yet, microwave imaging suffers from low spatial resolution. This work reviews
      conventional X-ray breast imaging and describes the preliminary results of a
      novel near-field radar imaging mechatronic system (NRIMS) that can be fused with
      the DBT, in a co-registered fashion, to combine the advantages of both
      modalities. The NRIMS consists of two antipodal Vivaldi antennas, an XY
      positioner, and an ethanol container, all of which are particularly designed
      based on the DBT physical specifications. In this paper, the independent
      performance of the NRIMS is assessed by (1) imaging a bearing ball immersed in
      sunflower oil and (2) computing the heat Specific Absorption Rate (SAR) due to
      the electromagnetic power transmitted into the breast. The preliminary results
      demonstrate that the system is capable of generating images of the ball.
      Furthermore, the SAR results show that the system complies with the standards set
      for human trials. As a result, a configuration based on this design might be
      suitable for use in realistic clinical applications.

PMID- 29370107
TI  - Nano/Mesoporous Carbon from Rice Starch for Voltammetric Detection of Ascorbic
      Acid.
AB  - Rice starch (RS-)based nano/mesoporous carbon (RSNMC) was prepared via a hard
      templating route using cheap rice starch as a carbon source. XRD and TEM
      characterization indicated the formation of organized nanoporous RSNMC. Nitrogen
      absorption-desorption studies revealed a high surface area of up to 488 m2?g-1,
      uniform pore size of 3.92 nm, and pore volume of 1.14 cm3?g-1. A RSNMC-modified
      glassy carbon (GC) electrode was employed for the determination of ascorbic acid
      (AA) and exhibited a linear response in the concentration range of 0.005-6.0 mM
      with a detection limit of 0.003 mM. These results demonstrate that RSNMC has
      potential as an advanced and cheap electrode material for electrochemical sensing
      and other electrocatalytic applications.

PMID- 29370108
TI  - Immunomodulatory Effect of Tremella Polysaccharides against Cyclophosphamide
      Induced Immunosuppression in Mice.
AB  - Polysaccharides are closely associated with immune regulation, but there are
      different polysaccharide effects from different sources. In this study, the aim
      was to investigate the effect of tremella polysaccharides (TP) in
      cyclophosphamide-induced immunodeficient mice. We observed the thymus and spleen
      index, liver and spleen pathological changes, and the levels of IL-2, IL-12, INF
      gamma, TGF-beta and Ig G in serum, and we also noted the mRNA expression of IL
      1beta, IL-4, IL-12 and TGF-beta in liver and spleen. Besides, we also measured
      the best effects of different doses of TP (Low-TP was 20 mg/kg.BW, Middle-TP was
      40 mg/kg.BW, and High-TP was 80 mg/kg.BW) on cyclophosphamide-induced
      immunosuppressed mice. The results were remarkable, and suggested that TP had a
      significant effect for enhancing immunity in cyclophosphamide-induced
      immunosuppression, and the immune enhancement of High-TP had the best results in
      TP-treated mice. It could significantly increase the thymus and spleen index,
      alleviate pathological features of immunosuppression such as the arrangement of
      liver sinusoid and hepatic plates was disordered, massive inflammatory cells
      infiltrated and fatty degeneration of hepatocytes in liver, and red pulp and
      white pulp were intermixed, splenic corpuscles demolished and disappeared,
      splenic sinusoid extended, and lymphocytes of spleen were reduced in spleen.
      Besides, it could also up-regulate serum levels of IL-2, IL-12, INF-gamma and Ig
      G, reduce the level of TGF-beta in serum, markedly promote mRNA expression of IL
      1beta, IL-4 and IL-12 in liver and spleen, and suppress mRNA expression of TGF
      beta. Above all, TP showed preventive effect for cyclophosphamide-induced
      immunosuppressed mice.

PMID- 29370109
TI  - Dual-Mode Gas Sensor Composed of a Silicon Nanoribbon Field Effect Transistor and
      a Bulk Acoustic Wave Resonator: A Case Study in Freons.
AB  - In this paper, we develop a novel dual-mode gas sensor system which comprises a
      silicon nanoribbon field effect transistor (Si-NR FET) and a film bulk acoustic
      resonator (FBAR). We investigate their sensing characteristics using polar and
      nonpolar organic compounds, and demonstrate that polarity has a significant
      effect on the response of the Si-NR FET sensor, and only a minor effect on the
      FBAR sensor. In this dual-mode system, qualitative discrimination can be achieved
      by analyzing polarity with the Si-NR FET and quantitative concentration
      information can be obtained using a polymer-coated FBAR with a detection limit at
      the ppm level. The complementary performance of the sensing elements provides
      higher analytical efficiency. Additionally, a dual mixture of two types of freons
      (CFC-113 and HCFC-141b) is further analyzed with the dual-mode gas sensor. Owing
      to the small size and complementary metal-oxide semiconductor (CMOS)
      compatibility of the system, the dual-mode gas sensor shows potential as a
      portable integrated sensing system for the analysis of gas mixtures in the
      future.

PMID- 29370111
TI  - A Pilot Study of Stress System Activation in Children Enrolled in a Targeted
      Prevention Program: Implications for Personalization.
AB  - : Empirically validated interventions addressing childhood psychological problems
      are now readily available, but success likely depends in part on accurately
      identifying which children will benefit from which intervention. This pilot study
      examined the stress activation and response system, first as a way to
      differentiate high versus low-risk children, and second to explore indicators of
      the stress system associated with favorable intervention response. METHOD:
      Participants (N = 43, 58% male) were school-aged children who qualified for
      inclusion in the Early Risers "Skills for Success" Prevention Program based on
      their elevated levels of aggressive and/or socially withdrawn behavior and a
      normally developing comparison group. Compared to the normally developing group,
      children who were participants in the intervention exhibited a more blunted
      cortisol response to the stress paradigm. However, for the children in the
      intervention group, elevated cortisol levels at the start of the stress paradigm
      were concurrently associated with internalizing problems and predictive of
      improvement in internalizing problems over time. These findings provide
      preliminary evidence that hypothalamic pituitary adrenal (HPA) axis biological
      variables may be helpful tools for identifying children who would benefit from
      intervention and personalizing interventions.

PMID- 29370112
TI  - A 3D-Printable Polymer-Metal Soft-Magnetic Functional Composite-Development and
      Characterization.
AB  - In this work, a 3D printed polymer-metal soft-magnetic composite was developed
      and characterized for its material, structural, and functional properties. The
      material comprises acrylonitrile butadiene styrene (ABS) as the polymer matrix,
      with up to 40 vol. % stainless steel micropowder as the filler. The composites
      were rheologically analyzed and 3D printed into tensile and flexural test
      specimens using a commercial desktop 3D printer. Mechanical characterization
      revealed a linearly decreasing trend of the ultimate tensile strength (UTS) and a
      sharp decrease in Young's modulus with increasing filler content. Four-point
      bending analysis showed a decrease of up to 70% in the flexural strength of the
      composite and up to a two-factor increase in the secant modulus of elasticity.
      Magnetic hysteresis characterization revealed retentivities of up to 15.6 mT and
      coercive forces of up to 4.31 kA/m at an applied magnetic field of 485 kA/m. The
      composite shows promise as a material for the additive manufacturing of passive
      magnetic sensors and/or actuators.

PMID- 29370110
TI  - Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and
      Application in Osteoporosis Treatment.
AB  - Osteoporosis is a progressive skeletal disease characterized by decreased bone
      mass and degraded bone microstructure, which leads to increased bone fragility
      and risks of bone fracture. Osteoporosis is generally age related and has become
      a major disease of the world. Uncovering the molecular mechanisms underlying
      osteoporosis and developing effective prevention and therapy methods has great
      significance for human health. Mesenchymal stem cells (MSCs) are multipotent
      cells capable of differentiating into osteoblasts, adipocytes, or chondrocytes,
      and have become the favorite source of cell-based therapy. Evidence shows that
      during osteoporosis, a shift of the cell differentiation of MSCs to adipocytes
      rather than osteoblasts partly contributes to osteoporosis. Thus, uncovering the
      molecular mechanisms of the osteoblast or adipocyte differentiation of MSCs will
      provide more understanding of MSCs and perhaps new methods of osteoporosis
      treatment. The MSCs have been applied to both preclinical and clinical studies in
      osteoporosis treatment. Here, we review the recent advances in understanding the
      molecular mechanisms regulating osteoblast differentiation and adipocyte
      differentiation of MSCs and highlight the therapeutic application studies of MSCs
      in osteoporosis treatment. This will provide researchers with new insights into
      the development and treatment of osteoporosis.

PMID- 29370113
TI  - Urinary Metabolite Levels of Flame Retardants in Electronic Cigarette Users: A
      Study Using the Data from NHANES 2013-2014.
AB  - Evaluating the safety of e-cigarettes and making informed judgement about
      developing potential standards require sufficient scientific evidence. Since e
      cigarettes are highly engineered products containing plastic, glass and metal
      parts, and e-liquids are largely different matrices, many toxic compounds which
      are not typical hazards for the users of combustible tobacco products (e.g.,
      cigarettes), could exist in e-liquids, and consequently, posing potential health
      risk to e-cigarette users. We combined the measurements of urinary metabolites of
      organophosphate flame retardants (OPFRs) with questionnaire data collected in the
      National Health and Nutrition Examination Surveys (NHANES) from 2013 to 2014, and
      we compared adjusted geometric means (GM) for each biomarker in e-cigarette users
      with levels in non-users and users of various tobacco products using multiple
      regression analyses to adjust for potential confounders. We found diphenyl
      phosphate (DPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2
      chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP) were detected in all
      e-cigarette users. The adjusted GM of BCEP, the metabolite of tris(2-chloroethyl)
      phosphate (TCEP), was 81% higher than nonusers (p = 0.0124) and significantly
      higher than those for both cigarette and cigar users (p < 0.05). The findings in
      this pilot study suggest that certain OPFRs may present in e-cigarettes as
      contaminants, and consequently, resulting in higher exposure levels in e
      cigarette users compared to nonusers. As we only identified 14 e-cigarette users
      in the survey, the findings in this study need to be confirmed in future study at
      a larger scale. A better examination of the types and levels of FRs and their
      potential contamination sources in e-cigarettes is also needed.

PMID- 29370114
TI  - Acidic Chitinase-Chitin Complex Is Dissociated in a Competitive Manner by Acetic
      Acid: Purification of Natural Enzyme for Supplementation Purposes.
AB  - Acidic chitinase (Chia) has been implicated in asthma, allergic inflammations,
      and food processing. We have purified Chia enzymes with striking acid stability
      and protease resistance from chicken and pig stomach tissues using a chitin
      column and 8 M urea (urea-Chia). Here, we report that acetic acid is a suitable
      agent for native Chia purification from the stomach tissues using a chitin column
      (acetic acid-Chia). Chia protein can be eluted from a chitin column using 0.1 M
      acetic acid (pH 2.8), but not by using Gly-HCl (pH 2.5) or sodium acetate (pH 4.0
      or 5.5). The melting temperatures of Chia are not affected substantially in the
      elution buffers, as assessed by differential scanning fluorimetry. Interestingly,
      acetic acid appears to be more effective for Chia-chitin dissociation than do
      other organic acids with similar structures. We propose a novel concept of this
      dissociation based on competitive interaction between chitin and acetic acid
      rather than on acid denaturation. Acetic acid-Chia also showed similar
      chitinolytic activity to urea-Chia, indicating that Chia is extremely stable
      against acid, proteases, and denaturing agents. Both acetic acid- and urea-Chia
      seem to have good potential for supplementation or compensatory purposes in
      agriculture or even biomedicine.

PMID- 29370115
TI  - Ethanol Extract of Oldenlandia diffusa Herba Attenuates Scopolamine-Induced
      Cognitive Impairments in Mice via Activation of BDNF, P-CREB and Inhibition of
      Acetylcholinesterase.
AB  - Though Oldenlandia diffusa Herba (ODH) has been known to exhibit anti-cancer and
      anti-inflammatory effects, its anti-amnestic effect has never been reported so
      far. The aim of this present study was to elucidate the anti-amnestic effect of
      ODH. ODH pretreatment significantly reduced escape latency of scopolamine treated
      Institute of Cancer Research (ICR) mice compared to untreated control groups in a
      Morris water maze test. Similarly, the passive avoidance test showed that ODH
      treatment recovered the scopolamine induced amnesia in the ICR mouse model.
      Concentration of Ach in brains of ODH treated mice was increased compared to that
      of scopolamine treated mice. In addition, activity of acetylcholinesterase (AChE)
      was notably decreased by ODH. The protein expression of brain-derived
      neurotrophic factor (BDNF) and phospho-cAMP response element-binding protein (p
      CREB) (Ser133) was increased in ODH pretreated group compared to control group.
      Consistently, immunohistochemistry (IHC) revealed the elevated expression of
      brain-derived neurotrophic factor (BDNF) and p-CREB in brains of ODH treated mice
      compared to the control group. Overall, these findings suggest that ODH has anti
      amnestic potential via activation of BDNF and p-CREB and inhibition of AChE in
      mice with scopolamine induced amnesia.

PMID- 29370117
TI  - Improved Intranasal Retentivity and Transnasal Absorption Enhancement by
      PEGylated Poly-l-ornithine.
AB  - We reported that the introduction of polyethylene glycol (PEG) to poly-l
      ornithine (PLO), which is an homopolymeric basic amino acid having absorption
      enhancement ability, prolonged retention time in an in vitro inclined plate test,
      probably due to an increase in viscosity caused by PEGylation. The aim of the
      present study is to investigate whether the introduction of PEG chains to PLO
      improves intranasal retention and transnasal absorption in vivo. We performed
      intranasal administration experiments using PLO and PEG-PLO with a model drug,
      fluorescein isothiocyanate dextran (FD-4), in rats under closed and open systems.
      In the open system, transition of plasma FD-4 concentration after co
      administration with unmodified PLO was low, and the area under the plasma
      concentration-time curve (AUC) decreased to about 60% of that in the closed
      system. In contrast, the AUC after co-administration with PEG-PLO in the open
      system was about 90% of that in the closed system, and the transition of plasma
      FD-4 concentration and FD-4 absorption profile were similar to those of the
      closed system. These findings indicate that introducing PEG chains to
      homopolymeric basic amino acids (HPBAAs) is a very useful method for developing a
      functional absorption enhancer that can exhibit an efficient in vivo absorption
      enhancing effect.

PMID- 29370116
TI  - Anti-Tumor and Radiosensitization Effects of N-Butylidenephthalide on Human
      Breast Cancer Cells.
AB  - N-Butylidenephthalide (BP), which is extracted from a traditional Chinese
      medicine, Radix Angelica Sinensis (danggui), displays antitumor activity against
      various cancer cell lines. The purpose of this study was to investigate the
      cytotoxic and radiosensitizing effect of BP and the underlying mechanism of
      action in human breast cancer cells. BP induces apoptosis in breast cancer cells,
      which was revealed by the TUNEL assay; the activation of caspase-9 and PARP was
      detected by western blot. In addition, BP-induced G2/M arrest was examined by
      flow cytometry and the expression levels of the G2/M regulatory protein were
      detected by western blot. BP also suppresses the migration and invasion of breast
      cancer cells, which was tested by wound healing and the matrigel invasion assay;
      the involvement of EMT-related gene expressions was detected by real-time PCR.
      Furthermore, BP enhanced the radiosensitivity of breast cancer cells, which was
      measured by the colony formation assay and comet assay, where the foci of gamma
      H2AX after radiation significantly increased in BP pretreated cells and was
      evidenced by immunocytochemistry staining and western blot. The homologous
      recombination (HR) repair protein Rad51 was down-regulated after BP pretreatment.
      These results indicate that BP might be a potential chemotherapeutic and
      radiosensitizing agent for breast cancer therapy.

PMID- 29370118
TI  - Evaluation of Trace Elements in Augmentation of Statin-Induced Cytotoxicity in
      Uremic Serum-Exposed Human Rhabdomyosarcoma Cells.
AB  - Patients with end-stage kidney disease (ESKD) are at higher risk for
      rhabdomyolysis induced by statin than patients with normal kidney function.
      Previously, we showed that this increase in the severity of statin-induced
      rhabdomyolysis was partly due to uremic toxins. However, changes in the quantity
      of various trace elements in ESKD patients likely contribute as well. The purpose
      of this study is to determine the effect of trace elements on statin-induced
      toxicity in rhabdomyosarcoma cells exposed to uremic serum (US cells) for a long
      time. Cell viability, apoptosis, mRNA expression, and intracellular trace
      elements were assessed by viability assays, flow cytometry, real-time RT-PCR, and
      ICP-MS, respectively. US cells exhibited greater simvastatin-induced cytotoxicity
      than cells long-time exposed with normal serum (NS cells) (non-overlapping 95%
      confidence intervals). Intracellular levels of Mg, Mn, Cu, and Zn were
      significantly less in US cells compared to that in NS cells (p < 0.05 or 0.01).
      Pre-treatment with TPEN increased simvastatin-induced cytotoxicity and eliminated
      the distinction between both cells of simvastatin-induced cytotoxicity. These
      results suggest that Zn deficiencies may be involved in the increased risk for
      muscle complaints in ESKD patients. In conclusion, the increased severity of
      statin-induced rhabdomyolysis in ESKD patients may be partly due to trace
      elements deficiencies.

PMID- 29370119
TI  - Inadequate Dietary Phosphorus Levels Cause Skeletal Anomalies and Alter
      Osteocalcin Gene Expression in Zebrafish.
AB  - Phosphorus (P) is an essential mineral for the development and maintenance of the
      vertebrate skeletal system. Modulation of P levels is believed to influence
      metabolism and the physiological responses of gene expression. In this study, we
      investigated the influence of dietary P on skeletal deformities and osteocalcin
      gene expression in zebrafish (Danio rerio), and sought to determine appropriate
      levels in a diet. We analyzed a total of 450 zebrafish within 31 days of
      hatching. Animals were distributed in a completely randomized experimental design
      that consisted of five replications. After an eight-week experiment, fish were
      diaphanized to evaluate cranial and spinal bone deformities. Increases in dietary
      phosphorus were inversely proportional to the occurrence of partial spine
      fusions, the absence of spine fusions, absence of parallelism between spines,
      intervertebral spacing, vertebral compression, scoliosis, lordosis, ankylosis,
      fin caudal insertion, and craniofacial deformities. Additionally, osteocalcin
      expression was inversely correlated to P levels, suggesting a physiological
      recovery response for bone mineralization deficiency. Our data showed that
      dietary P concentration was a critical factor in the occurrence of zebrafish
      skeletal abnormalities. We concluded that 1.55% P in the diet significantly
      reduces the appearance of skeletal deformities and favors adequate bone
      mineralization through the adjustment of osteocalcin expression.

PMID- 29370120
TI  - Effects of Multivitamin, Multimineral and Phytonutrient Supplementation on
      Nutrient Status and Biomarkers of Heart Health Risk in a Russian Population: A
      Randomized, Double Blind, Placebo Controlled Study.
AB  - The primary objective of this clinical study was to evaluate the effect of a
      dietary multivitamin, multimineral and phytonutrient (VMP) supplement on blood
      nutrient status and biomarkers of heart health risk in a Russian population. One
      hundred twenty healthy adults (40-70 years) were recruited for a 56-day (eight
      week) randomized, double blind, placebo controlled study with parallel design.
      Subjects were divided into two groups and received either a VMP or a placebo
      (PLA) supplement. Blood nutrient levels of beta-carotene, alpha-tocopherol,
      vitamin C, B6, B12, red blood cell (RBC) folate, Zinc and Selenium were measured
      at baseline and on Days 28 and 56, and quercetin was measured at baseline and on
      Day 56. Blood biomarkers of heart health, i.e. homocysteine (Hcy), high
      sensitivity C-reactive protein (hs-CRP), oxidized LDL (ox-LDL), gamma-glutamyl
      transferase (GGT), uric acid and blood lipid profile, were measured at baseline
      and Day 56. Dietary VMP supplementation for 56 days significantly increased
      circulating levels of quercetin, vitamin C, RBC folate and partially prevented
      the decline in vitamin B6 and B12 status. Both serum Hcy and GGT were
      significantly reduced (-3.97 +/- 10.09 umol/L; -1.68 +/- 14.53 U/L, respectively)
      after VMP supplementation compared to baseline. Dietary VMP supplementation
      improved the nutrient status and reduced biomarkers of heart health risk in a
      Russian population.

PMID- 29370121
TI  - Polymorphisms/Mutations in A-Kinase Anchoring Proteins (AKAPs): Role in the
      Cardiovascular System.
AB  - A-kinase anchoring proteins (AKAPs) belong to a family of scaffolding proteins
      that bind to protein kinase A (PKA) by definition and a variety of crucial
      proteins, including kinases, phosphatases, and phosphodiesterases. By scaffolding
      these proteins together, AKAPs build a "signalosome" at specific subcellular
      locations and compartmentalize PKA signaling. Thus, AKAPs are important for
      signal transduction after upstream activation of receptors ensuring accuracy and
      precision of intracellular PKA-dependent signaling pathways. Since their
      discovery in the 1980s, AKAPs have been studied extensively in the heart and have
      been proven essential in mediating cyclic adenosine monophosphate (cAMP)-PKA
      signaling. Although expression of AKAPs in the heart is very low, cardiac
      specific knock-outs of several AKAPs have a noteworthy cardiac phenotype.
      Moreover, single nucleotide polymorphisms and genetic mutations in crucial
      cardiac proteins play a substantial role in the pathophysiology of cardiovascular
      diseases (CVDs). Despite the significant role of AKAPs in the cardiovascular
      system, a limited amount of research has focused on the role of genetic
      polymorphisms and/or mutations in AKAPs in increasing the risk of CVDs. This
      review attempts to overview the available literature on the
      polymorphisms/mutations in AKAPs and their effects on human health with a special
      focus on CVDs.

PMID- 29370122
TI  - Minoxidil Skin Delivery from Nanoemulsion Formulations Containing Eucalyptol or
      Oleic Acid: Enhanced Diffusivity and Follicular Targeting.
AB  - In this work, we examined enhanced skin delivery of minoxidil applied in
      nanoemulsions incorporating skin penetration enhancers. Aliquots of fully
      characterized oil-in-water nanoemulsions (1 mL), containing minoxidil (2%) and
      the skin penetration enhancer oleic acid or eucalyptol as oil phases, were
      applied to full-thickness excised human skin in Franz diffusion cells, while
      aqueous solutions (1 mL) containing minoxidil were used as controls. Minoxidil in
      the stratum corneum (SC), hair follicles, deeper skin layers, and flux through
      the skin over 24 h was determined, as well as minoxidil solubility in the
      formulations and in the SC. The nanoemulsions significantly enhanced the
      permeation of minoxidil through skin compared with control solutions. The
      eucalyptol formulations (NE) promoted minoxidil retention in the SC and deeper
      skin layers more than did the oleic acid formulations, while the oleic acid
      formulations (NO) gave the greatest hair follicle penetration. Minoxidil maximum
      flux enhancement was associated with increases in both minoxidil SC solubility
      and skin diffusivity in both nanoemulsion systems. The mechanism of enhancement
      appeared to be driven largely by increased diffusivity, rather than increased
      partitioning into the stratum corneum, supporting the concept of enhanced
      fluidity and disruption of stratum corneum lipids.

PMID- 29370123
TI  - Three-Dimensional Hepatocellular Carcinoma/Fibroblast Model on a Nanofibrous
      Membrane Mimics Tumor Cell Phenotypic Changes and Anticancer Drug Resistance.
AB  - Three-dimensional (3D) in vitro tissue or organ models can effectively mimic the
      complex microenvironment of many types of human tissues for medical applications.
      Unfortunately, development of 3D cancer models, which involve cancer/stromal
      cells in a 3D environment, has remained elusive due to the extreme complexity of
      the tumor microenvironment (TME) and the stepwise progression of human cancer.
      Here, we developed hepatocellular carcinoma (HCC) models, which consist of
      fibroblasts as stromal cells, HCC cells, and a nanofibrous membrane to mimic the
      complex TME. The 3D HCC models were fabricated using three distinct culture
      methods: cancer cells grown directly on the nanofibrous membrane (mono model),
      fibroblasts covering the nanofibrous membrane (layer model), and both cancer
      cells and fibroblasts grown on the nanofibrous membrane (mixed model).
      Interestingly, the mono model and layer model showed similar tissue structures,
      whereas the mixed model resulted in phenotypic changes to the cancer cells.
      Further analysis demonstrated that the mixed models promoted the expression of
      fibronectin and vimentin, and showed higher resistance to anticancer drugs
      compared with the other models. Thus, our 3D HCC model could be utilized for
      testing efficient anticancer therapies at various stages of cancer, with
      potential application to different tumor types.

PMID- 29370125
TI  - The Effect of Surface Confined Gold Nanoparticles in Blocking the Extraction of
      Nitrate by PVC-Based Polymer Inclusion Membranes Containing Aliquat 336 as the
      Carrier.
AB  - Clusters of gold nanoparticles (AuNPs) formed on the surface of PVC-based polymer
      inclusion membranes (PIMs) with a liquid phase containing Aliquat 336 as the
      carrier and in some cases 1-dodecanol or 2-nitrophenol octyl ether as
      plasticizers were found to inhibit the extraction of nitrate by the PIMs. This
      observation was based on gradually increasing the mass of AuNPs on the membrane
      surface and testing the ability of the membrane to extract nitrate after each
      increase. In this way, it was possible to determine the so-called "critical AuNP
      masses" at which the studied membranes ceased to extract nitrate. On the basis of
      these results, it can be hypothesized that the surfaces of these PIMs are not
      homogeneous with respect to the distribution of their membrane liquid phases,
      which are present only at certain sites. Extraction takes place only at these
      sites, and at the "critical AuNP mass" of a PIM, all these extraction sites are
      blocked and the membrane loses its ability to extract.

PMID- 29370126
TI  - Size-Dependent Affinity of Glycine and Its Short Oligomers to Pyrite Surface: A
      Model for Prebiotic Accumulation of Amino Acid Oligomers on a Mineral Surface.
AB  - The interaction strength of progressively longer oligomers of glycine, (Gly), di
      Gly, tri-Gly, and penta-Gly, with a natural pyrite surface was directly measured
      using the force mode of an atomic force microscope (AFM). In recent years,
      selective activation of abiotically formed amino acids on mineral surfaces,
      especially that of pyrite, has been proposed as an important step in many origins
      of life scenarios. To investigate such notions, we used AFM-based force
      measurements to probe possible non-covalent interactions between pyrite and amino
      acids, starting from the simplest amino acid, Gly. Although Gly itself interacted
      with the pyrite surface only weakly, progressively larger unbinding forces and
      binding frequencies were obtained using oligomers from di-Gly to penta-Gly. In
      addition to an expected increase of the configurational entropy and size
      dependent van der Waals force, the increasing number of polar peptide bonds,
      among others, may be responsible for this observation. The effect of chain length
      was also investigated by performing similar experiments using l-lysine vs. poly-l
      lysine (PLL), and l-glutamic acid vs. poly-l-glutamic acid. The results suggest
      that longer oligomers/polymers of amino acids can be preferentially adsorbed on
      pyrite surfaces.

PMID- 29370127
TI  - Food Acquisition through Private and Public Social Networks and Its Relationship
      with Household Food Security among Various Socioeconomic Statuses in South Korea.
AB  - This study was conducted to understand food acquisition practices from social
      networks and its relationship with household food security. In-depth interviews
      and a survey on food security were conducted with twenty-nine mothers and one
      father in metropolitan areas of South Korea. Many families acquired food from
      their extended families, mainly participants' mothers. Between low-income and non
      low-income households, there was a pattern of more active sharing of food through
      private networks among non-low-income households. Most of the low-income
      households received food support from public social networks, such as government
      and charity institutions. Despite the assistance, most of them perceived food
      insecurity. We hypothesized that the lack of private social support may
      exacerbate the food security status of low-income households, despite formal food
      assistance from government and social welfare institutions. Interviews revealed
      that certain food items were perceived as lacking, such as animal-based protein
      sources and fresh produce, which are relatively expensive in this setting. Future
      programs should consider what would alleviate food insecurity among low-income
      households and determine the right instruments and mode of resolving the unmet
      needs. Future research could evaluate the quantitative relationship between
      private resources and food insecurity in households with various income statuses.

PMID- 29370128
TI  - Recent Advances in Nanoporous Membranes for Water Purification.
AB  - Nanoporous materials exhibit wide applications in the fields of electrocatalysis,
      nanodevice fabrication, energy, and environmental science, as well as analytical
      science. In this review, we present a summary of recent studies on nanoporous
      membranes for water purification application. The types and fabrication
      strategies of various nanoporous membranes are first introduced, and then the
      fabricated nanoporous membranes for removing various water pollutants, such as
      salt, metallic ions, anions, nanoparticles, organic chemicals, and biological
      substrates, are demonstrated and discussed. This work will be valuable for
      readers to understand the design and fabrication of various nanoporous membranes,
      and their potential purification mechanisms towards different water pollutants.
      In addition, it will be helpful for developing new nanoporous materials for
      quick, economic, and high-performance water purification.

PMID- 29370129
TI  - Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients
      with Rheumatoid Arthritis.
AB  - A natural killer group 2 member D (NKG2D) acts as a powerful activating and co
      stimulatory receptor on immune effector cells including NK and T cells.
      Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune
      response and promote autoimmune reactions. The objective of the study was to
      evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor
      of how effective anti-tumor necrosis factor (TNF) therapy is in rheumatoid
      arthritis (RA) patients. A total of 280 RA patients receiving anti-TNF therapy
      were genotyped for NKG2D rs2255336 (A > G), rs1049174 (C > G), and rs1154831 (C >
      A). Clinical response was evaluated according to the European League against
      Rheumatism (EULAR) criteria at the 12th and 24th week. Both the NKG2D rs225336
      and rs1049174 polymorphisms were significantly associated with efficacy of TNF
      inhibitors. Inefficient therapy was more frequently observed in patients with
      rs2255336 GG or rs1049174 CC genotype as compared to other genotypes (p-value =
      0.003 and p-value = 0.004, respectively). The presence of the rs2255336 G or the
      rs1049174 C allele correlated with a worse EULAR response (p-value = 0.002, p
      value = 0.031, respectively). Moreover, patients carrying the rs2255336 or
      rs1049174 heterozygous genotype achieved better EULAR responses than patients
      with homozygous genotypes (p-value = 0.010 and p-value = 0.002, respectively).
      Data from the present study provides evidence that NKG2D polymorphisms may affect
      response to anti-TNF inhibitors in RA patients.

PMID- 29370130
TI  - Revealing Grain Boundary Sliding from Textures of a Deformed Nanocrystalline Pd
      Au Alloy.
AB  - Employing a recent modeling scheme for grain boundary sliding [Zhao et al. Adv.
      Eng. Mater.2017, doi:10.1002/adem.201700212], crystallographic textures were
      simulated for nanocrystalline fcc metals deformed in shear compression. It is
      shown that, as grain boundary sliding increases, the texture strength decreases
      while the signature of the texture type remains the same. Grain boundary sliding
      affects the texture components differently with respect to intensity and angular
      position. A comparison of a simulation and an experiment on a Pd-10 atom % Au
      alloy with a 15 nm grain size reveals that, at room temperature, the predominant
      deformation mode is grain boundary sliding contributing to strain by about 60%.

PMID- 29370131
TI  - Multispecies Adulteration Detection of Camellia Oil by Chemical Markers.
AB  - Adulteration of edible oils has attracted attention from more researchers and
      consumers in recent years. Complex multispecies adulteration is a commonly used
      strategy to mask the traditional adulteration detection methods. Most of the
      researchers were only concerned about single targeted adulterants, however, it
      was difficult to identify complex multispecies adulteration or untargeted
      adulterants. To detect adulteration of edible oil, identification of
      characteristic markers of adulterants was proposed to be an effective method,
      which could provide a solution for multispecies adulteration detection. In this
      study, a simple method of multispecies adulteration detection for camellia oil
      (adulterated with soybean oil, peanut oil, rapeseed oil) was developed by
      quantifying chemical markers including four isoflavones, trans-resveratrol and
      sinapic acid, which used liquid chromatography tandem mass spectrometry (LC
      MS/MS) combined with solid phase extraction (SPE). In commercial camellia oil,
      only two of them were detected of daidzin with the average content of 0.06 ng/g
      while other markers were absent. The developed method was highly sensitive as the
      limits of detection (LODs) ranged from 0.02 ng/mL to 0.16 ng/mL and the mean
      recoveries ranged from 79.7% to 113.5%, indicating that this method was reliable
      to detect potential characteristic markers in edible oils. Six target compounds
      for pure camellia oils, soybean oils, peanut oils and rapeseed oils had been
      analyzed to get the results. The validation results indicated that this simple
      and rapid method was successfully employed to determine multispecies adulteration
      of camellia oil adulterated with soybean, peanut and rapeseed oils.

PMID- 29370132
TI  - Study of the Direct Red 81 Dye/Copper(II)-Phenanthroline System.
AB  - Recovered papers contain several chromophores, such as wood lignin and dyes.
      These have to be eliminated during paper recycling in order to produce white
      paper. Hydrogen peroxide under alkaline conditions is generally used to
      decolorize lignin, but its effect on dyes is limited. Copper(II)-phenanthroline
      (Cu-Phen) complexes can activate the oxidation of lignin by hydrogen peroxide.
      Hydrogen peroxide may also be activated during recycled fiber bleaching, thus
      enhancing its color-stripping efficiency towards unoxidizable azo dyes. The
      purpose of this paper was to determine the effect of Cu-Phen complexes on a model
      azo dye, Direct Red 81 (DR81), in aqueous solution. Different Cu-Phen solutions
      (with different initial Cu:Phen molar ratios) were prepared and mixed with the
      dye at different pHs. The geochemical computer program PHREEQC allowed precise
      calculation of the theoretical distribution between different possible
      coordinates (CuPhenOH+, Cu(Phen)22+, CuPhen(OH)2, Cu(Phen)32+, etc.) depending on
      pH and initial concentrations. UV-vis spectroscopic measurements were correlated
      with the major species theoretically present in each condition. The UV absorbance
      of the system was mainly attributed to the Cu-Phen complex and the visible
      absorbance was only due to the dye. Cu-Phen appeared to reduce the color
      intensity of the DR81 dye aqueous solution under specific conditions (more
      effective at pH 10.7 with Cu:Phen = 1:1), probably owing to the occurrence of a
      coordination phenomenon between DR81 and Cu-Phen. Hence, the ligand competition
      between phenanthroline and hydroxide ions would be disturbed by a third
      competitor, which is the dye molecule. Further investigation proved that the DR81
      dye is able to form a complex with copper-phenanthroline, leading to partial
      color-stripping. This new "color-stripping effect" may be a new opportunity in
      paper and textile industries for wastewater treatment.

PMID- 29370133
TI  - HPLC-PDA Combined with Chemometrics for Quantitation of Active Components and
      Quality Assessment of Raw and Processed Fruits of Xanthium strumarium L.
AB  - As a valuable herbal medicine, the fruits of Xanthium strumarium L. (Xanthii
      Fructus) have been widely used in raw and processed forms to achieve different
      therapeutic effects in practice. In this study, a comprehensive strategy was
      proposed for evaluating the active components in 30 batches of raw and processed
      Xanthii Fructus (RXF and PXF) samples, based on high-performance liquid
      chromatography coupled with photodiode array detection (HPLC-PDA). Twelve common
      peaks were detected and eight compounds of caffeoylquinic acids were
      simultaneously quantified in RXF and PXF. All the analytes were detected with
      satisfactory linearity (R2 > 0.9991) over wide concentration ranges.
      Simultaneously, the chemically latent information was revealed by hierarchical
      cluster analysis (HCA) and principal component analysis (PCA). The results
      suggest that there were significant differences between RXF and PXF from
      different regions in terms of the content of eight caffeoylquinic acids.
      Potential chemical markers for XF were found during processing by chemometrics.

PMID- 29370134
TI  - Trace Elements in Soils and Selected Agricultural Plants in the Tongling Mining
      Area of China.
AB  - The quality and safety of agricultural products from metal mining areas are of
      wide concern. In order to investigate the contents and health risks of trace
      elements in fruit vegetables planted in metal mining areas, 440 samples of fruit
      vegetables from 117 vegetable plots were collected from Tongling mining area.
      Trace element contents in fruit vegetables and soil were measured. The results
      indicated that the total concentration of trace elements in some of the soil
      samples exceeded the Grade II national standard in China. Transfer factor (TF) of
      Cd was the highest (8.360), followed by Zn, Cu, As, and Pb. Estimated daily
      intake (EDI) of the trace elements, except Cd, were generally below the maximum
      tolerable daily intake (MTDI). The target hazard quotient (THQ) of Zn for
      children was more than 1 in some vegetables, suggesting potential health hazards
      for child population. Total target hazard quotient (TTHQ) of Cu and Zn were also
      more than 1 through consumption of all vegetables, indicating significant health
      risks. For both adults and children, hazard index (HI) was more than 1 for the
      consumption of vegetables. The findings reveal the health risks associated with
      the consumption of trace elements through the intake of selected vegetables in
      the population of Tongling.

PMID- 29370135
TI  - The Weakening of Kin Ties: Exploring the Need for Life-World Led Interventions.
AB  - The protective features that families and wider social relationships can have are
      required to meet the demands of life in contemporary Western societies. Choice
      and detraditionalization, however; impede this source of solidarity. Family Group
      Conferencing (FGC) and other life-world led interventions have the potential to
      strengthen primary groups. This paper explores the need for such a social
      intervention, using insights from sociological and philosophical theories and
      empirical findings from a case study of the research project 'FGC in mental
      health'. This need is understandable considering the weakening of kin ties, the
      poor qualities of state agencies to mobilise self-care and informal care, its
      capacity to produce a shift of power from public to private spheres and its
      capacity to mitigate the co-isolation of individuals, families and communities. A
      life-world led intervention like FGC with a specific and modest ambition
      contributes to small-scale solidarity. This ambition is not inclined to establish
      a broad social cohesion within society but to restore; in terms of the German
      philosopher Peter Sloterdijk; immunity (protection) and solidarity in primary
      groups, and consequently, resolve issues with those (family, neighbours,
      colleagues) who share a sphere (a situation, a process, a fate).

PMID- 29370136
TI  - Assessment of Tomato (Solanum lycopersicum L.) Producers' Exposure Level to
      Pesticides, in Kouka and Toussiana (Burkina Faso).
AB  - To assess producers' exposure level to pesticides in vegetable production in
      Burkina Faso, a study was carried out in 2016 and 2017 among 30 tomato producers
      in the municipalities of Kouka and Toussiana. Eighteen (18) commercial
      formulations were identified, with more than 50% of pesticides destined for
      cotton production. Eleven active substances have been identified and the most
      frequently used are lambda-cyhalothrin (35%), acetamiprid (22%) and profenofos
      (13%). The most commonly used chemical families are pyrethroids (28%) and
      organophosphates (18%). The study revealed a low level of training for producers,
      a high use of pesticides according to the Frequency Treatment Indicator, and a
      very low level of protection used by producers. The Health Risk Index shows that
      active substances such as methomyl, lambda-cyhalothrin and profenofos present
      very high risk to operators' health. Based on the UK-POEM model, the predictive
      exposure levels obtained varied from 0.0105 mg/kg body weight/day to 1.7855 mg/kg
      body weight/day, which is several times higher than the Acceptable Operator
      Exposure Level. However, the study also shows that exposure can be greatly
      reduced if the required Personal Protective Equipment is worn. Producers'
      awareness and training on integrated pest management are necessary to reduce the
      risks linked to the pesticides use in Burkina Faso.

PMID- 29370138
TI  - A Novel Noncircular MUSIC Algorithm Based on the Concept of the Difference and
      Sum Coarray.
AB  - In this paper, we propose a vectorized noncircular MUSIC (VNCM) algorithm based
      on the concept of the coarray, which can construct the difference and sum (diff
      sum) coarray, for direction finding of the noncircular (NC) quasi-stationary
      sources. Utilizing both the NC property and the concept of the Khatri-Rao
      product, the proposed method can be applied to not only the ULA but also sparse
      arrays. In addition, we utilize the quasi-stationary characteristic instead of
      the spatial smoothing method to solve the coherent issue generated by the Khatri
      Rao product operation so that the available degree of freedom (DOF) of the
      constructed virtual array will not be reduced by half. Compared with the
      traditional NC virtual array obtained in the NC MUSIC method, the diff-sum
      coarray achieves a higher number of DOFs as it comprises both the difference set
      and the sum set. Due to the complementarity between the difference set and the
      sum set for the coprime array, we choose the coprime array with multiperiod
      subarrays (CAMpS) as the array model and summarize the properties of the
      corresponding diff-sum coarray. Furthermore, we develop a diff-sum coprime array
      with multiperiod subarrays (DsCAMpS) whose diff-sum coarray has a higher DOF.
      Simulation results validate the effectiveness of the proposed method and the high
      DOF of the diff-sum coarray.

PMID- 29370137
TI  - Impact of an Outdoor Smoking Ban at Secondary Schools on Cigarettes, E-Cigarettes
      and Water Pipe Use among Adolescents: An 18-Month Follow-Up.
AB  - Abstract: The effectiveness of outdoor smoking bans on smoking behavior among
      adolescents remains inconclusive. This study evaluates the long-term impact of
      outdoor school ground smoking bans among adolescents at secondary schools on the
      use of conventional cigarettes, e-cigarettes (with/without nicotine) and water
      pipes. Outdoor smoking bans at 19 Dutch secondary schools were evaluated using a
      quasi-experimental design. Data on 7733 adolescents were obtained at baseline,
      and at 6 and 18-month follow-up. The impact of outdoor smoking bans on 'ever use
      of conventional cigarettes', 'smoking onset', 'ever use of e-cigarette with
      nicotine', 'e-cigarette without nicotine', and 'water pipe' was measured.
      Multilevel logistic regression analysis was used. At schools with a ban,
      implementation fidelity was checked. At schools where a ban was implemented, at
      18-month follow-up more adolescents had started smoking compared to the control
      condition. No effect of implementation of the ban was found for smoking
      prevalence, e-cigarettes with/without nicotine, and water pipe use.
      Implementation fidelity was sufficient. No long-term effects were found of an
      outdoor smoking ban, except for smoking onset. The ban might cause a reversal
      effect when schools encounter difficulties with its enforcement or when
      adolescents still see others smoking. Additional research is required with a
      longer follow-up than 18 months.

PMID- 29370139
TI  - Three-Dimensional Blood Vessel Model with Temperature-Indicating Function for
      Evaluation of Thermal Damage during Surgery.
AB  - Surgical simulators have recently attracted attention because they enable the
      evaluation of the surgical skills of medical doctors and the performance of
      medical devices. However, thermal damage to the human body during surgery is
      difficult to evaluate using conventional surgical simulators. In this study, we
      propose a functional surgical model with a temperature-indicating function for
      the evaluation of thermal damage during surgery. The simulator is made of a
      composite material of polydimethylsiloxane and a thermochromic dye, which
      produces an irreversible color change as the temperature increases. Using this
      material, we fabricated a three-dimensional blood vessel model using the lost-wax
      process. We succeeded in fabricating a renal vessel model for simulation of
      catheter ablation. Increases in the temperature of the materials can be measured
      by image analysis of their color change. The maximum measurement error of the
      temperature was approximately -1.6  degrees C/+2.4  degrees C within the range of
      60  degrees C to 100  degrees C.

PMID- 29370140
TI  - A Novel Single-Axis MEMS Tilt Sensor with a High Sensitivity in the Measurement
      Range from 0? to 360?.
AB  - In this paper, a novel single-axis MEMS tilt sensor is presented. It contains a
      hexagonal proof mass, six micro-lever force amplifiers and three double-ended
      tuning fork (DETF) resonant strain gauges. The proof mass is placed in the center
      with the micro-levers and the DETFs radially arrayed around. The variation of
      gravity acceleration applied on the proof mass will result in frequency shifts of
      the DETFs. Angular tilt can be got by analyzing the frequency outputs. The
      structural design of the tilt sensor is optimized by finite element simulation
      and the device is microfabricated using a silicon-on-insulator process, followed
      by open-loop and closed-loop characterizations. Results show that the scale
      factor of such sensor is at least 11.53 Hz/degree. Minimum Allan deviation of the
      DETF oscillator is 220 ppb (parts per billion) of the resonant frequency for an 5
      s integration time. Resolution of the tilt sensor is 0.002 ? in the whole
      measurement range from 0 ? to 360 ? .

PMID- 29370141
TI  - VLSI Design of Trusted Virtual Sensors.
AB  - This work presents a Very Large Scale Integration (VLSI) design of trusted
      virtual sensors providing a minimum unitary cost and very good figures of size,
      speed and power consumption. The sensed variable is estimated by a virtual sensor
      based on a configurable and programmable PieceWise-Affine hyper-Rectangular
      (PWAR) model. An algorithm is presented to find the best values of the
      programmable parameters given a set of (empirical or simulated) input-output
      data. The VLSI design of the trusted virtual sensor uses the fast authenticated
      encryption algorithm, AEGIS, to ensure the integrity of the provided virtual
      measurement and to encrypt it, and a Physical Unclonable Function (PUF) based on
      a Static Random Access Memory (SRAM) to ensure the integrity of the sensor
      itself. Implementation results of a prototype designed in a 90-nm Complementary
      Metal Oxide Semiconductor (CMOS) technology show that the active silicon area of
      the trusted virtual sensor is 0.86 mm 2 and its power consumption when trusted
      sensing at 50 MHz is 7.12 mW. The maximum operation frequency is 85 MHz, which
      allows response times lower than 0.25 MU s. As application example, the designed
      prototype was programmed to estimate the yaw rate in a vehicle, obtaining root
      mean square errors lower than 1.1%. Experimental results of the employed PUF show
      the robustness of the trusted sensing against aging and variations of the
      operation conditions, namely, temperature and power supply voltage (final value
      as well as ramp-up time).

PMID- 29370142
TI  - High Frequency Data Acquisition System for Modelling the Impact of Visitors on
      the Thermo-Hygrometric Conditions of Archaeological Sites: A Casa di Diana (Ostia
      Antica, Italy) Case Study.
AB  - The characterization of the microclimatic conditions is fundamental for the
      preventive conservation of archaeological sites. In this context, the
      identification of the factors that influence the thermo-hygrometric equilibrium
      is key to determine the causes of cultural heritage deterioration. In this work,
      a characterization of the thermo-hygrometric conditions of Casa di Diana (Ostia
      Antica, Italy) is carried out analyzing the data of temperature and relative
      humidity recorded by a system of sensors with high monitoring frequency. Sensors
      are installed in parallel, calibrated and synchronized with a microcontroller. A
      data set of 793,620 data, arranged in a matrix with 66,135 rows and 12 columns,
      was used. Furthermore, the influence of human impact (visitors) is evaluated
      through a multiple linear regression model and a logistic regression model. The
      visitors do not affect the environmental humidity as it is very high and constant
      all the year. The results show a significant influence of the visitors in the
      upset of the thermal balance. When a tourist guide takes place, the probability
      that the hourly temperature variation reaches values higher than its monthly
      average is 10.64 times higher than it remains equal or less to its monthly
      average. The analysis of the regression residuals shows the influence of outdoor
      climatic variables in the thermal balance, such as solar radiation or
      ventilation.

PMID- 29370143
TI  - Post-Exercise Carbohydrate-Energy Replacement Attenuates Insulin Sensitivity and
      Glucose Tolerance the Following Morning in Healthy Adults.
AB  - The carbohydrate deficit induced by exercise is thought to play a key role in
      increased post-exercise insulin action. However, the effects of replacing
      carbohydrate utilized during exercise on postprandial glycaemia and insulin
      sensitivity are yet to be determined. This study therefore isolated the extent to
      which the insulin-sensitizing effects of exercise are dependent on the
      carbohydrate deficit induced by exercise, relative to other exercise-mediated
      mechanisms. Fourteen healthy adults performed a 90-min run at 70% V  O 2 max
      starting at 1600-1700 h before ingesting either a non-caloric artificially
      sweetened placebo solution (CHO-DEFICIT) or a 15% carbohydrate solution (CHO
      REPLACE; 221.4 +/- 59.3 g maltodextrin) to precisely replace the measured
      quantity of carbohydrate oxidized during exercise. The alternate treatment was
      then applied one week later in a randomized, placebo-controlled, and double
      blinded crossover design. A standardized low-carbohydrate evening meal was
      consumed in both trials before overnight recovery ahead of a two-hour oral
      glucose tolerance test (OGTT) the following morning to assess glycemic and
      insulinemic responses to feeding. Compared to the CHO-DEFICIT condition, CHO
      REPLACE increased the incremental area under the plasma glucose curve by a mean
      difference of 68 mmol.L-1 (95% CI: 4 to 132 mmol.L-1; p = 0.040) and decreased
      the Matsuda insulin sensitivity index by a mean difference of -2 au (95% CI: -1
      to -3 au; p = 0.001). This is the first study to demonstrate that post-exercise
      feeding to replaceme the carbohydrate expended during exercise can attenuate
      glucose tolerance and insulin sensitivity the following morning. The mechanism
      through which exercise improves insulin sensitivity is therefore (at least in
      part) dependent on carbohydrate availability and so the day-to-day metabolic
      health benefits of exercise might be best attained by maintaining a carbohydrate
      deficit overnight.

PMID- 29370144
TI  - Pre-Meal Effect of Whey Proteins on Metabolic Parameters in Subjects with and
      without Type 2 Diabetes: A Randomized, Crossover Trial.
AB  - Diabetic dyslipidemia with elevated postprandial triglyceride (TG) responses is
      characteristic in type 2 diabetes (T2D). Diet and meal timing can modify
      postprandial lipemia (PPL). The impact of a pre-meal of whey proteins (WP) on
      lipid metabolism is unidentified. We determined whether a WP pre-meal prior to a
      fat-rich meal influences TG and apolipoprotein B-48 (ApoB-48) responses
      differentially in patients with and without T2D. Two matched groups of 12
      subjects with and without T2D accomplished an acute, randomized, cross-over
      trial. A pre-meal of WP (20 g) or water (control) was consumed 15 min before a
      fat-rich meal (supplemented with 20 g WP in case of water pre-meal). Postprandial
      responses were examined during a 360-min period. A WP pre-meal significantly
      increased postprandial concentrations of insulin (P < 0.0001), glucagon (P <
      0.0001) and glucose-dependent insulinotropic peptide (GIP) (P < 0.0001) in
      subjects with and without T2D. We detected no effects of the WP pre-meal on TG,
      ApoB-48, or non-esterified fatty acids (NEFA) responses to the fat-rich meal in
      either group. Paracetamol absorption i.e. gastric emptying was delayed by the WP
      pre-meal (P = 0.039). In conclusion, the WP pre-meal induced similar hormone and
      lipid responses in subjects with and without T2D. Thus, the WP pre-meal enhanced
      insulin, glucagon and GIP responses but did not influence lipid or glucose
      responses. In addition, we demonstrated that a WP pre-meal reduced gastric
      emptying in both groups.

PMID- 29370145
TI  - Establishing a Pharmacy-Based Patient Registry System: A Pilot Study for
      Evaluating Pharmacist Intervention for Patients with Long-Term Medication Use.
AB  - Background: In Japan, an increasing number of patients are prescribed a large
      amount of long-term medications by large hospitals that are then dispensed by a
      community pharmacy. This practice often leads to considerable wastage of
      medicine. As part of their professional role, community pharmacists are expected
      to contribute more to the appropriate use of medication by patients. Using a
      prospective cohort, we aimed to evaluate pharmacists' role in the community.
      Methods: We created a patient registry system for community pharmacies to monitor
      long-term medication use by patients with chronic conditions. Patient drug
      adherence and potential problems were monitored through regular home visits or
      telephone calls by the pharmacist at least once a month between patient hospital
      visits. Patient data were collected and stored in an internet-based system.
      Results: Over a one-year follow-up, 28 out of 37 registered patients from 14
      community pharmacies were continuously monitored. In total, we extracted 19
      problems relating to medication use, 17 to physical complaints, eight to patient
      concerns, and two others. Conclusion: The registry system was useful for
      identifying medication-related problems as well as patient concerns and changes
      in their condition. Pharmacists might play a key role in improving patient care
      in the community.

PMID- 29370146
TI  - Development of Low Parasitic Light Sensitivity and Low Dark Current 2.8 MUm
      Global Shutter Pixel.
AB  - Abstract: We developed a low parasitic light sensitivity (PLS) and low dark
      current 2.8 MUm global shutter pixel. We propose a new inner lens design concept
      to realize both low PLS and high quantum efficiency (QE). 1/PLS is 7700 and QE is
      62% at a wavelength of 530 nm. We also propose a new storage-gate based memory
      node for low dark current. P-type implants and negative gate biasing are
      introduced to suppress dark current at the surface of the memory node. This
      memory node structure shows the world smallest dark current of 9.5 e-/s at 60 
      degrees C.

PMID- 29370147
TI  - Antifungal Activity of Commercial Essential Oils and Biocides against Candida
      Albicans.
AB  - Management of oral candidosis, most frequently caused by Candida albicans, is
      limited due to the relatively low number of antifungal drugs and the emergence of
      antifungal tolerance. In this study, the antifungal activity of a range of
      commercial essential oils, two terpenes, chlorhexidine and triclosan was
      evaluated against C. albicans in planktonic and biofilm form. In addition,
      cytotoxicity of the most promising compounds was assessed using murine
      fibroblasts and expressed as half maximal inhibitory concentrations (IC50).
      Antifungal activity was determined using a broth microdilution assay. The minimum
      inhibitory concentration (MIC) was established against planktonic cells cultured
      in a range of concentrations of the test agents. The minimal biofilm eradication
      concentration (MBEC) was determined by measuring re-growth of cells after pre
      formed biofilm was treated for 24 h with the test agents. All tested commercial
      essential oils demonstrated anticandidal activity (MICs from 0.06% (v/v) to 0.4%
      (v/v)) against planktonic cultures, with a noticeable increase in resistance
      exhibited by biofilms (MBECs > 1.5% (v/v)). The IC50s of the commercial essential
      oils were lower than the MICs, while a one hour application of chlorhexidine was
      not cytotoxic at concentrations lower than the MIC. In conclusion, the tested
      commercial essential oils exhibit potential as therapeutic agents against C.
      albicans, although host cell cytotoxicity is a consideration when developing
      these new treatments.

PMID- 29370148
TI  - The Enhanced Red Emission and Improved Thermal Stability of CaAlSiN3:Eu2+
      Phosphors by Using Nano-EuB6 as Raw Material.
AB  - Synthesizing phosphors with high performance is still a necessary work for
      phosphor-converted white light-emitting diodes (W-LEDs). In this paper, three
      series of CaAlSiN3:Eu2+ (denoted as CASN:Eu2+) phosphors using Eu2O3, EuN and
      EuB6 as raw materials respectively are fabricated by under the alloy precursor
      normal pressure nitridation synthesis condition. We demonstrate that CASN:Eu2+
      using nano-EuB6 as raw material shows higher emission intensity than others,
      which is ascribed to the increment of Eu2+ ionic content entering into the
      crystal lattice. An improved thermal stability can also be obtained by using nano
      EuB6 due to the structurally stable status, which is assigned to the partial
      substitution of Eu-O (Eu-N) bonds by more covalent Eu-B ones that leads to a
      higher structural rigidity. In addition, the W-LEDs lamp was fabricated to
      explore its possible application in W-LEDs based on blue LEDs. Our results
      indicate that using EuB6 as raw materials can provide an effective way of
      enhancing the red emission and improving the thermal stability of the CASN:Eu2+
      red phosphor.

PMID- 29370150
TI  - State-Specific Prevalence of Tobacco Product Use Among Adults - United States,
      2014-2015.
AB  - Despite recent declines in cigarette smoking prevalence, the tobacco product
      landscape has shifted to include emerging tobacco products* (1,2). Previous
      research has documented adult use of smokeless tobacco and cigarettes by state
      (3); however, state-specific data on other tobacco products are limited. To
      assess tobacco product use in the 50 U.S. states and the District of Columbia
      (DC), CDC and the National Cancer Institute analyzed self-reported use of six
      tobacco product types: cigarettes, cigars, regular pipes, water pipes, electronic
      cigarettes (e-cigarettes), and smokeless tobacco products among adults aged >=18
      years using data from the 2014-2015 Tobacco Use Supplement to the Current
      Population Survey (TUS-CPS). Prevalence of ever-use of any tobacco product ranged
      from 27.0% (Utah) to 55.4% (Wyoming). Current (every day or some days) use of any
      tobacco product ranged from 10.2% (California) to 27.7% (Wyoming). Cigarettes
      were the most common currently used tobacco product in all states and DC. Among
      current cigarette smokers, the proportion who currently used one or more other
      tobacco products ranged from 11.5% (Delaware) to 32.3% (Oregon). Differences in
      tobacco product use across states underscore the importance of implementing
      proven population-level strategies to reduce tobacco use and expanding these
      strategies to cover all forms of tobacco marketed in the United States. Such
      strategies could include comprehensive smoke-free policies, tobacco product price
      increases, anti-tobacco mass media campaigns, and barrier-free access to clinical
      smoking cessation resources (1,4).

PMID- 29370149
TI  - A Systematic Review and Meta-Analysis of Mindfulness-Based (Baduanjin) Exercise
      for Alleviating Musculoskeletal Pain and Improving Sleep Quality in People with
      Chronic Diseases.
AB  - OBJECTIVE: we performed the first systematic review with meta-analyses of the
      existing studies that examined mindfulness-based Baduanjin exercise for its
      therapeutic effects for individuals with musculoskeletal pain or insomnia.
      METHODS: Both English- (PubMed, Web of Science, Elsevier, and Google Scholar) and
      Chinese-language (CNKI and Wangfang) electronic databases were used to search
      relevant articles. We used a modified PEDro scale to evaluate risk of bias across
      studies selected. All eligible RCTS were considered for meta-analysis. The
      standardized mean difference was calculated for the pooled effects to determine
      the magnitude of the Baduanjin intervention effect. For the moderator analysis,
      we performed subgroup meta-analysis for categorical variables and meta-regression
      for continuous variables. RESULTS: The aggregated result has shown a significant
      benefit in favour of Baduanjin at alleviating musculoskeletal pain (SMD = -0.88,
      95% CI -1.02 to -0.74, p < 0.001, I2 = 10.29%) and improving overall sleep
      quality (SMD = -0.48, 95% CI -0.95 to -0.01, p = 004, I2 = 84.42%). CONCLUSIONS:
      Mindfulness-based Baduanjin exercise may be effective for alleviating
      musculoskeletal pain and improving overall sleep quality in people with chronic
      illness. Large, well-designed RCTs are needed to confirm these findings.

PMID- 29370151
TI  - Population-Based Surveillance of Birth Defects Potentially Related to Zika Virus
      Infection - 15 States and U.S. Territories, 2016.
AB  - Zika virus infection during pregnancy can cause serious birth defects, including
      microcephaly and brain abnormalities (1). Population-based birth defects
      surveillance systems are critical to monitor all infants and fetuses with birth
      defects potentially related to Zika virus infection, regardless of known exposure
      or laboratory evidence of Zika virus infection during pregnancy. CDC analyzed
      data from 15 U.S. jurisdictions conducting population-based surveillance for
      birth defects potentially related to Zika virus infection.* Jurisdictions were
      stratified into the following three groups: those with 1) documented local
      transmission of Zika virus during 2016; 2) one or more cases of confirmed,
      symptomatic, travel-associated Zika virus disease reported to CDC per 100,000
      residents; and 3) less than one case of confirmed, symptomatic, travel-associated
      Zika virus disease reported to CDC per 100,000 residents. A total of 2,962
      infants and fetuses (3.0 per 1,000 live births; 95% confidence interval [CI] =
      2.9-3.2) (2) met the case definition.? In areas with local transmission there was
      a non-statistically significant increase in total birth defects potentially
      related to Zika virus infection from 2.8 cases per 1,000 live births in the first
      half of 2016 to 3.0 cases in the second half (p = 0.10). However, when neural
      tube defects and other early brain malformations (NTDs)S were excluded, the
      prevalence of birth defects strongly linked to congenital Zika virus infection
      increased significantly, from 2.0 cases per 1,000 live births in the first half
      of 2016 to 2.4 cases in the second half, an increase of 29 more cases than
      expected (p = 0.009). These findings underscore the importance of surveillance
      for birth defects potentially related to Zika virus infection and the need for
      continued monitoring in areas at risk for Zika.

PMID- 29370152
TI  - Recommendations of the Advisory Committee on Immunization Practices for Use of
      Herpes Zoster Vaccines.
AB  - On October 20, 2017, Zoster Vaccine Recombinant, Adjuvanted (Shingrix,
      GlaxoSmithKline, [GSK] Research Triangle Park, North Carolina), a 2-dose, subunit
      vaccine containing recombinant glycoprotein E in combination with a novel
      adjuvant (AS01B), was approved by the Food and Drug Administration for the
      prevention of herpes zoster in adults aged >=50 years. The vaccine consists of 2
      doses (0.5 mL each), administered intramuscularly, 2-6 months apart (1). On
      October 25, 2017, the Advisory Committee on Immunization Practices (ACIP)
      recommended the recombinant zoster vaccine (RZV) for use in immunocompetent
      adults aged >=50 years.

PMID- 29370153
TI  - Notes from the Field: Errors in Administration of an Excess Dosage of Yellow
      Fever Vaccine - United States, 2017.

PMID- 29370154
TI  - Short Sleep Duration Among Middle School and High School Students - United
      States, 2015.
AB  - Insufficient sleep among children and adolescents is associated with increased
      risk for obesity, diabetes, injuries, poor mental health, attention and behavior
      problems, and poor academic performance (1-4). The American Academy of Sleep
      Medicine has recommended that, for optimal health, children aged 6-12 years
      should regularly sleep 9-12 hours per 24 hours and teens aged 13-18 years should
      sleep 8-10 hours per 24 hours (1). CDC analyzed data from the 2015 national,
      state, and large urban school district Youth Risk Behavior Surveys (YRBSs) to
      determine the prevalence of short sleep duration (<9 hours for children aged 6-12
      years and <8 hours for teens aged 13-18 years) on school nights among middle
      school and high school students in the United States. In nine states that
      conducted the middle school YRBS and included a question about sleep duration in
      their questionnaire, the prevalence of short sleep duration among middle school
      students was 57.8%, with state-level estimates ranging from 50.2% (New Mexico) to
      64.7% (Kentucky). The prevalence of short sleep duration among high school
      students in the national YRBS was 72.7%. State-level estimates of short sleep
      duration for the 30 states that conducted the high school YRBS and included a
      question about sleep duration in their questionnaire ranged from 61.8% (South
      Dakota) to 82.5% (West Virginia). The large percentage of middle school and high
      school students who do not get enough sleep on school nights suggests a need for
      promoting sleep health in schools and at home and delaying school start times to
      permit students adequate time for sleep.

PMID- 29370155
TI  - QuickStats: Percentage* of Emergency Department Visits for Acute Viral Upper
      Respiratory Tract Infection? That Had an Antimicrobial Ordered or Prescribed,S by
      Metropolitan Statistical Area  - United States, 2008-2015*.
AB  - From 2008-2011 to 2012-2015, the percentage of visits for acute viral upper
      respiratory tract infection that had an antimicrobial ordered or prescribed
      decreased from 37.1% to 25.5% among emergency departments (EDs) located in
      nonmetropolitan statistical areas, but this decline was not seen among EDs in
      metropolitan statistical areas. In 2008-2011, the percentage was higher among
      nonmetropolitan EDs than metropolitan EDs, but there was no difference in 2012
      2015.

PMID- 29370156
TI  - CRISPR/Cas9 genome editing in human hematopoietic stem cells.
AB  - Genome editing via homologous recombination (HR) (gene targeting) in human
      hematopoietic stem cells (HSCs) has the power to reveal gene-function
      relationships and potentially transform curative hematological gene and cell
      therapies. However, there are no comprehensive and reproducible protocols for
      targeting HSCs for HR. Herein, we provide a detailed protocol for the production,
      enrichment, and in vitro and in vivo analyses of HR-targeted HSCs by combining
      CRISPR/Cas9 technology with the use of rAAV6 and flow cytometry. Using this
      protocol, researchers can introduce single-nucleotide changes into the genome or
      longer gene cassettes with the precision of genome editing. Along with our
      troubleshooting and optimization guidelines, researchers can use this protocol to
      streamline HSC genome editing at any locus of interest. The in vitro HSC
      targeting protocol and analyses can be completed in 3 weeks, and the long-term in
      vivo HSC engraftment analyses in immunodeficient mice can be achieved in 16
      weeks. This protocol enables manipulation of genes for investigation of gene
      functions during hematopoiesis, as well as for the correction of genetic
      mutations in HSC transplantation-based therapies for diseases such as sickle cell
      disease, beta-thalassemia, and primary immunodeficiencies.

PMID- 29370157
TI  - Mass cytometry analysis of immune cells in the brain.
AB  - Immune cells comprise a diverse and dynamic cell population that is responsible
      for a broad range of immunological activities. They act in concert with other
      immune and nonimmune cells via cytokine-mediated communication and direct cell
      cell interactions. Understanding the complex immune network requires a broad
      characterization of its individual cellular components. This is especially
      relevant for the brain compartment, which is an active immunological site,
      composed of resident and infiltrating immune cells that affect brain development,
      tissue homeostasis and neuronal activity. Mass cytometry, or CyTOF (cytometry by
      time-of-flight), uses metal-conjugated antibodies to enable a high-dimensional
      description of tens of markers at the single-cell level, thereby providing a
      bird's-eye view of the immune system. This technique has been successfully
      applied to the discovery of novel immune populations in humans and rodents. Here,
      we provide a step-by-step description of a mass cytometry approach for the
      analysis of the mouse brain compartment. The different stages of the procedure
      include brain perfusion, extraction of the brain tissue and its dissociation into
      a single-cell suspension, followed by cell staining with metal-tagged antibodies,
      sample reading using a mass cytometer, and data analysis using SPADE and viSNE.
      This procedure takes <5 h (excluding data analysis) and can be applied to study
      modifications in the brain's immune populations under normal and pathological
      conditions.

PMID- 29370159
TI  - Hot mitochondria?
AB  - Mitochondria generate most of the heat in endotherms. Given some impedance of
      heat transfer across protein-rich bioenergetic membranes, mitochondria must
      operate at a higher temperature than body temperature in mammals and birds. But
      exactly how much hotter has been controversial, with physical calculations
      suggesting that maximal heat gradients across cells could not be greater than 10
      5 K. Using the thermosensitive mitochondrial-targeted fluorescent dye Mito Thermo
      Yellow (MTY), Chretien and colleagues suggest that mitochondria are optimised to
      nearly 50  degrees C, 10  degrees C hotter than body temperature. This extreme
      value questions what temperature really means in confined far-from-equilibrium
      systems but encourages a reconsideration of thermal biology.

PMID- 29370160
TI  - Correction: Regulating toxic chemicals for public and environmental health.
AB  - [This corrects the article DOI: 10.1371/journal.pbio.2004814.].

PMID- 29370158
TI  - Heat-induced radiolabeling and fluorescence labeling of Feraheme nanoparticles
      for PET/SPECT imaging and flow cytometry.
AB  - Feraheme (FH) nanoparticles (NPs) have been used extensively for treatment of
      iron anemia (due to their slow release of ionic iron in acidic environments). In
      addition, injected FH NPs are internalized by monocytes and function as MRI
      biomarkers for the pathological accumulation of monocytes in disease. We have
      recently expanded these applications by radiolabeling FH NPs for positron
      emission tomography (PET) or single-photon emission computed tomography (SPECT)
      imaging using a heat-induced radiolabeling (HIR) strategy. Imaging FH NPs using
      PET/SPECT has important advantages over MRI due to lower iron doses and improved
      quantitation of tissue NP concentrations. HIR of FH NPs leaves the physical and
      biological properties of the NPs unchanged and allows researchers to build on the
      extensive knowledge obtained about the pharmacokinetic and safety aspects of FH
      NPs. In this protocol, we present the step-by-step procedures for heat (120 
      degrees C)-induced bonding of three widely employed radiocations (89Zr4+ or
      64Cu2+ for PET, and 111In3+ for SPECT) to FH NPs using a chelateless radiocation
      surface adsorption (RSA) approach. In addition, we describe the conversion of FH
      carboxyl groups into amines and their reaction with an N-hydroxysuccinimide (NHS)
      of a Cy5.5 fluorophore. This yields Cy5.5-FH, a fluorescent FH that enables the
      cells internalizing Cy5.5-FH to be examined using flow cytometry. Finally, we
      describe procedures for in vivo and ex vivo uptake of Cy5.5-FH by monocytes and
      for in vivo microPET/CT imaging of HIR-FH NPs. Synthesis of HIR-FH requires
      experience with working with radioactive cations and can be completed within <4
      h. Synthesis of Cy5.5-FH NPs takes ~17 h.

PMID- 29370161
TI  - CRL4 antagonizes SCFFbxo7-mediated turnover of cereblon and BK channel to
      regulate learning and memory.
AB  - Intellectual disability (ID), one of the most common human developmental
      disorders, can be caused by genetic mutations in Cullin 4B (Cul4B) and cereblon
      (CRBN). CRBN is a substrate receptor for the Cul4A/B-DDB1 ubiquitin ligase (CRL4)
      and can target voltage- and calcium-activated BK channel for ER retention. Here
      we report that ID-associated CRL4CRBN mutations abolish the interaction of the BK
      channel with CRL4, and redirect the BK channel to the SCFFbxo7 ubiquitin ligase
      for proteasomal degradation. Glioma cell lines harbouring CRBN mutations record
      density-dependent decrease of BK currents, which can be restored by blocking
      Cullin ubiquitin ligase activity. Importantly, mice with neuron-specific deletion
      of DDB1 or CRBN express reduced BK protein levels in the brain, and exhibit
      similar impairment in learning and memory, a deficit that can be partially
      rescued by activating the BK channel. Our results reveal a competitive targeting
      of the BK channel by two ubiquitin ligases to achieve exquisite control of its
      stability, and support changes in neuronal excitability as a common pathogenic
      mechanism underlying CRL4CRBN-associated ID.

PMID- 29370162
TI  - Mind the gap! Risk factors for poor continuity of care of TB patients discharged
      from a hospital in the Western Cape, South Africa.
AB  - BACKGROUND: TB patients discharged from hospitals in South Africa experience poor
      continuity of care, failing to continue TB treatment at other levels of care.
      Factors contributing to poor continuity of TB care are insufficiently described
      to inform interventions. OBJECTIVE: To describe continuity of care and risk
      factors in TB patients discharged from a referral hospital in the Western Cape,
      South Africa. DESIGN: This retrospective observational study used routine
      information to describe continuity of care and risk factors in TB patients
      discharged from hospital. RESULTS: 788 hospitalized TB patients were identified
      in 6 months. Their median age was 32 years, 400 (51%) were male, and 653 (83%)
      were urban. A bacteriological TB test was performed for 74%, 25% were tested for
      HIV in hospital, and 32% of all TB patients had documented evidence of HIV co
      infection. Few (13%) were notified for TB; 375 (48%) received TB medication; 284
      (36%) continued TB treatment after discharge; 91 (24%) had a successful TB
      treatment outcome, and 166 (21%) died. Better continuity of care was associated
      with adults, urban residence, bacteriological TB tests in hospital and TB
      medication on discharge. Fragmented hospital TB data systems did not provide
      continuity with primary health care information systems. CONCLUSIONS: Discharged
      TB patients experienced poor continuity of care, with children, rural patients,
      those not tested for TB in hospital or discharged without TB medication at
      greatest risk. Suboptimal quality of hospital TB care and a fragmented hospital
      information system without linkages to other levels underpinned poor continuity
      of care.

PMID- 29370163
TI  - In vitro effects of two silicate-based materials, Biodentine and BioRoot RCS, on
      dental pulp stem cells in models of reactionary and reparative dentinogenesis.
AB  - BACKGROUND: Calcium silicate-based cements are biomaterials with calcium oxide
      and carbonate filler additives. Their properties are close to those of dentin,
      making them useful in restorative dentistry and endodontics. The aim of this
      study was to evaluate the in vitro biological effects of two such calcium
      silicate cements, Biodentine (BD) and Bioroot (BR), on dental stem cells in both
      direct and indirect contact models. The two models used aimed to mimic reparative
      dentin formation (direct contact) and reactionary dentin formation (indirect
      contact). An original aspect of this study is the use of an interposed thin
      agarose gel layer to assess the effects of diffusible components from the
      materials. RESULTS: The two biomaterials were compared and did not modify dental
      pulp stem cell (DPSC) proliferation. BD and BR showed no significant
      cytotoxicity, although some cell death occurred in direct contact. No apoptosis
      or inflammation induction was detected. A striking increase of mineralization
      induction was observed in the presence of BD and BR, and this effect was greater
      in direct contact. Surprisingly, biomineralization occurred even in the absence
      of mineralization medium. This differentiation was accompanied by expression of
      odontoblast-associated genes. Exposure by indirect contact did not stimulate the
      induction to such a level. CONCLUSION: These two biomaterials both seem to be
      bioactive and biocompatible, preserving DPSC proliferation, migration and
      adhesion. The observed strong mineralization induction through direct contact
      highlights the potential of these biomaterials for clinical application in dentin
      pulp complex regeneration.

PMID- 29370164
TI  - European starlings use their acute vision to check on feline predators but not on
      conspecifics.
AB  - Head movements allow birds with laterally placed eyes to move their centers of
      acute vision around and align them with objects of interest. Consequently, head
      movements have been used as indicator of fixation behavior (where gaze is
      maintained). However, studies on head movement behavior have not elucidated the
      degree to which birds use high-acuity or low-acuity vision. We studied how
      European starlings (Sturnus vulgaris) used high-acuity vision in the early stages
      of visual exploration of a stuffed cat (common terrestrial predator), a taxidermy
      Cooper's hawk (common aerial predator), and a stuffed study skin of a
      conspecific. We found that starlings tended to use their high acuity vision when
      looking at predators, particularly, the cat was above chance levels. However,
      when they viewed a conspecific, they used high acuity vision as expected by
      chance. We did not observe a preference for the left or right center of acute
      vision. Our findings suggest that starlings exposed to a predator (particularly
      cats) may employ selective attention by using high-acuity vision to obtain
      quickly detailed information useful for a potential escape, but exposed to a
      social context may use divided attention by allocating similar levels high- and
      low-quality vision to monitor both conspecifics and the rest of the environment.

PMID- 29370165
TI  - PLOS NTDs celebrates our 10th anniversary: Looking forward to the next decade.

PMID- 29370166
TI  - Expanding molecular diagnostics of helminthiasis: Piloting use of the GPLN
      platform for surveillance of soil transmitted helminthiasis and schistosomiasis
      in Ghana.
AB  - The efforts to control and eradicate polio as a global health burden have been
      successful to the point where currently only three countries now report endemic
      polio, and the number of cases of polio continues to decrease. The success of the
      polio programme has been dependant on a well-developed network of laboratories
      termed the global polio laboratory network (GPLN). Here we explore collaborative
      opportunities with the GPLN to target two of the 18 diseases listed as a
      neglected tropical diseases (NTD) namely soil transmitted helminthiasis (STH) and
      Schistosomiasis (SCH). These were chosen based on prevalence and the use of
      faecal materials to identify both polio, STH and SCH. Our study screened 448
      faecal samples from the Ghana GPLN using three triplex TaqMan assays to identify
      Ascaris lumbricoides, Necator americanus, Ancylostoma spp, Trichuris trchiura,
      Strongyloides stercoralis and Schistosoma spp. Our results found a combined
      helminth prevalence of 22%. The most common helminth infection was A.
      lumbricoides with a prevalence of 15% followed by N. americanus (5%), Ancylostoma
      spp. (2.5%), Schistosoma spp. (1.6%) and S. stercoralis (1%). These results show
      that it is possible to identify alternative pathogens to polio in the samples
      collected by the GPLN platform and to introduce new diagnostic assays to their
      laboratories. The diagnostic methods employed were also able to identify S.
      stercoralis positive samples, which are difficult to identify using
      parasitological methods such as Kato-Katz. This study raises the possibility of
      collaboration with the GPLN for the surveillance of a wider range of diseases
      which would both benefit the efforts to control the NTDs and also increase the
      scope of the GPLN as a diagnostic platform.

PMID- 29370167
TI  - Mitochondria are physiologically maintained at close to 50  degrees C.
AB  - In endothermic species, heat released as a product of metabolism ensures stable
      internal temperature throughout the organism, despite varying environmental
      conditions. Mitochondria are major actors in this thermogenic process. Part of
      the energy released by the oxidation of respiratory substrates drives ATP
      synthesis and metabolite transport, but a substantial proportion is released as
      heat. Using a temperature-sensitive fluorescent probe targeted to mitochondria,
      we measured mitochondrial temperature in situ under different physiological
      conditions. At a constant external temperature of 38  degrees C, mitochondria
      were more than 10  degrees C warmer when the respiratory chain (RC) was fully
      functional, both in human embryonic kidney (HEK) 293 cells and primary skin
      fibroblasts. This differential was abolished in cells depleted of mitochondrial
      DNA or treated with respiratory inhibitors but preserved or enhanced by
      expressing thermogenic enzymes, such as the alternative oxidase or the uncoupling
      protein 1. The activity of various RC enzymes was maximal at or slightly above 50
      degrees C. In view of their potential consequences, these observations need to
      be further validated and explored by independent methods. Our study prompts a
      critical re-examination of the literature on mitochondria.

PMID- 29370169
TI  - Interventions to maximize facial cleanliness and achieve environmental
      improvement for trachoma elimination: A review of the grey literature.
AB  - BACKGROUND: Efforts are underway to scale-up the facial cleanliness and
      environmental improvement (F&E) components of the World Health Organization's
      SAFE strategy for elimination of trachoma as a public health problem. Improving
      understanding of the F&E intervention landscape could inform advancements prior
      to scale-up, and lead to more effective and sustained behavior change.
      METHODS/FINDINGS: We systematically searched for relevant grey literature
      published from January 1965 through August 2016. Publications were eligible for
      review if they described interventions addressing F&E in the context of trachoma
      elimination programs. Subsequent to screening, we mapped attributes of F&E
      interventions. We then employed three behavior change frameworks to synthesize
      mapped data and identify potential intervention gaps. We identified 27 documents
      meeting inclusion criteria. With the exception of some recent programming, F&E
      interventions have largely focused on intermediate and distal antecedents of
      behavior change. Evidence from our analyses suggests many interventions are not
      designed to address documented determinants of improved F&E practices. No
      reviewed documents endorsed inclusion of intervention components related to
      behavioral maintenance or resilience-factors critical for sustaining improved
      behaviors. CONCLUSIONS: If left unaddressed, identified gaps in intervention
      content may continue to challenge uptake and sustainability of improved F&E
      behaviors. Stakeholders designing and implementing trachoma elimination programs
      should review their F&E intervention content and delivery approaches with an eye
      toward improvement, including better alignment with established behavior change
      theories and empirical evidence. Implementation should move beyond information
      dissemination, and appropriately employ a variety of behavior change techniques
      to address more proximal influencers of change.

PMID- 29370168
TI  - A switch in the mode of Wnt signaling orchestrates the formation of germline stem
      cell differentiation niche in Drosophila.
AB  - Germline stem cell (GSC) self-renewal and differentiation into gametes is
      regulated by both intrinsic factors in the germ line as well as extrinsic factors
      from the surrounding somatic niche. dWnt4, in the escort cells of the adult
      somatic niche promotes GSC differentiation using the canonical beta-catenin
      dependent transcriptional pathway to regulate escort cell survival, adhesion to
      the germ line and downregulation of self-renewal signaling. Here, we show that in
      addition to the beta-catenin-dependent canonical pathway, dWnt4 also uses
      downstream components of the Wnt non-canonical pathway to promote escort cell
      function earlier in development. We find that the downstream non-canonical
      components, RhoA, Rac1 and cdc42, are expressed at high levels and are active in
      escort cell precursors of the female larval gonad compared to the adult somatic
      niche. Consistent with this expression pattern, we find that the non-canonical
      pathway components function in the larval stages but not in adults to regulate
      GSC differentiation. In the larval gonad, dWnt4, RhoA, Rac1 and cdc42 are
      required to promote intermingling of escort cell precursors, a function that then
      promotes proper escort cell function in the adults. We find that dWnt4 acts by
      modulating the activity of RhoA, Rac1 and cdc42, but not their protein levels.
      Together, our results indicate that at different points of development, dWnt4
      switches from using the non-canonical pathway components to using a beta-catenin
      dependent canonical pathway in the escort cells to facilitate the proper
      differentiation of GSCs.

PMID- 29370170
TI  - Emerging trends of Zika apprehension in an epidemic setting.
AB  - BACKGROUND: French Guiana is a territory that has a decades-long history of
      dengue outbreaks and more recently, in 2014, a chikungunya outbreak. Zika virus
      (ZIKV) emerged in late 2015 and subsequently led to an important outbreak.
      METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional phone survey was conducted
      among the general population during the outbreak in June 2016 with a total of
      1,129 individuals interviewed to assess perceptions, knowledge and behaviors
      regarding zika infection. The population seemed aware of zika, and perceived the
      infection as a more serious health threat than other common mosquito-borne
      diseases. Furthermore, both the perceptions and behaviors related to zika and its
      prevention were found to vary considerably among different social groups,
      geographic areas and gender; less educated female participants were found to
      perceive the disease as more worrisome and were less likely to adopt protective
      behaviors. Moreover, female population has been particularly responsive to
      awareness campaigns and rapidly understood the extent of risks associated with
      ZIKV infection. CONCLUSIONS/SIGNIFICANCE: These results revealed that ZIKV
      appeared at the time of the survey as a new health threat that concerns the
      public more than chikungunya and dengue fever with differences observed among
      subgroups of population. These results have implications for the development of
      multifaceted infection control programs, including strategies for prevention and
      awareness, helping the population to develop an accurate perception of the threat
      they are facing and encouraging behavior changes.

PMID- 29370171
TI  - The complex scenario of obesity, diabetes and hypertension in the area of
      influence of primary healthcare facilities in Mexico.
AB  - INTRODUCTION: Among non-communicable chronic diseases (NCCD), diabetes and
      hypertension are the main cause of adult mortality worldwide. Among the members
      of the Organization for Economic Cooperation and Development, Mexico is first in
      prevalence of diabetes and second in obesity. To face this problematic situation
      of NCCDs the Ministry of Health declared a national epidemiological alert against
      the overweight, obesity and diabetes. The target of this study is to characterize
      the status of obesity, diabetes and hypertension in the adult population in the
      area of influence of primary health facilities located in high social marginality
      areas. METHODS: We conducted a cross-sectional observational study and used a
      convenience sample. A survey was conducted on a population of 18 years old and
      above in four primary health facilities in four Mexican States. The survey
      explored sociodemographic characteristics, the presence of chronic diseases, the
      access to healthcare services, risk factors and life styles. We also applied a
      complementary questionnaire to 20% of the participants, in order to explore food
      consumption during the last week and physical activity (International Physical
      Activity Questionnaire). We based our analysis on descriptive statistics and
      logistic multivariate regression to analyze factors associated with diabetes and
      hypertension. RESULTS: 73% (n = 7531, CI 0.72-0.74) percent of the population
      reported being diabetic, hypertensive and/or overweight. The majority of them
      receive healthcare in public health services. People over 40 years old, are 11
      times more probable of living with diabetes and 8.7 times more probable of living
      with hypertension. Both conditions affect mostly women, whose main activity is to
      be a housewife. People who have lunch and dinner out of home are more likely to
      develop diabetes. People who perform intense physical activity are less likely to
      live with hypertension. CONCLUSION: According to the self-report, more than 70%
      of adult population living in areas with high social marginality suffer diabetes,
      hypertension and obesity. However, the percentage of people who live with these
      chronic conditions and are not aware of them, is unknown. The Mexican health
      system needs a primary healthcare that emphasizes on health promotion, timely
      detection of risk factors of Non Communicable Diseases and prevention of their
      complications.

PMID- 29370172
TI  - Insular Celtic population structure and genomic footprints of migration.
AB  - Previous studies of the genetic landscape of Ireland have suggested homogeneity,
      with population substructure undetectable using single-marker methods. Here we
      have harnessed the haplotype-based method fineSTRUCTURE in an Irish genome-wide
      SNP dataset, identifying 23 discrete genetic clusters which segregate with
      geographical provenance. Cluster diversity is pronounced in the west of Ireland
      but reduced in the east where older structure has been eroded by historical
      migrations. Accordingly, when populations from the neighbouring island of Britain
      are included, a west-east cline of Celtic-British ancestry is revealed along with
      a particularly striking correlation between haplotypes and geography across both
      islands. A strong relationship is revealed between subsets of Northern Irish and
      Scottish populations, where discordant genetic and geographic affinities reflect
      major migrations in recent centuries. Additionally, Irish genetic proximity of
      all Scottish samples likely reflects older strata of communication across the
      narrowest inter-island crossing. Using GLOBETROTTER we detected Irish admixture
      signals from Britain and Europe and estimated dates for events consistent with
      the historical migrations of the Norse-Vikings, the Anglo-Normans and the British
      Plantations. The influence of the former is greater than previously estimated
      from Y chromosome haplotypes. In all, we paint a new picture of the genetic
      landscape of Ireland, revealing structure which should be considered in the
      design of studies examining rare genetic variation and its association with
      traits.

PMID- 29370173
TI  - Mast cell heterogeneity underlies different manifestations of food allergy in
      mice.
AB  - Food can trigger a diverse array of symptoms in food allergic individuals from
      isolated local symptoms affecting skin or gut to multi-system severe reactions
      (systemic anaphylaxis). Although we know that gastrointestinal and systemic
      manifestations of food allergy are mediated by tissue mast cells (MCs), it is not
      clear why allergen exposure by the oral route can result in such distinct
      clinical manifestations. Our aim was to assess the contribution of mast cell
      subsets to different manifestations of food allergy. We used two common models of
      IgE-mediated food allergy, one resulting in systemic anaphylaxis and the other
      resulting in acute gastrointestinal symptoms, to study the immune basis of
      allergic reactions. We used responders and non-responders in each model system,
      as well as naive controls to identify the association of mast cell activation
      with clinical reactivity rather than sensitization. Systemic anaphylaxis was
      uniquely associated with activation of connective tissue mast cells (identified
      by release of mouse mast cell protease (MMCP) -7 into the serum) and release of
      histamine, while activation of mucosal mast cells (identified by release of MMCP
      1 in the serum) did not correlate with symptoms. Gastrointestinal manifestations
      of food allergy were associated with an increase of MMCP-1-expressing mast cells
      in the intestine, and evidence of both mucosal and connective tissue mast cell
      activation. The data presented in this paper demonstrates that mast cell
      heterogeneity is an important contributor to manifestations of food allergy, and
      identifies the connective tissue mast cell subset as key in the development of
      severe systemic anaphylaxis.

PMID- 29370174
TI  - How psychosocial outcomes impact on the self-reported health status in type 2
      diabetes patients: Findings from the Diabetes Attitudes, Wishes and Needs (DAWN)
      study in eastern China.
AB  - INTRODUCTION: The deleterious effects of psychosocial outcomes on diabetic
      patients' health have not been fully investigated yet. This study was aimed to
      explore how psychosocial outcomes impacted on the health status of Chinese
      patients with type 2 diabetes. METHODS: A mix of stratified sampling and typical
      sampling were used to select diabetic patients in Jiangsu Province to conduct
      individual interviews. Health status was measured by EuroQol Visual Analogue
      Scale (VAS). Psychosocial outcomes were measured by instruments used in the
      Diabetes Attitudes, Wishes and Needs survey, including psychological well-being,
      diabetes distress, patient empowerment, self-management, and patient reported
      healthcare provision. Clinical characteristics measured included diabetes
      comorbidities, complications and treatment. OLS regression analyses were used to
      estimate how health status varied with different characteristics. RESULTS:
      Altogether 1614 patients with type 2 diabetes aged 18-65 years from 6
      districts/counties in Jiangsu Province were included in the study. With general
      characteristics and clinical factors controlled for, psychological well-being
      among all psychosocial outcomes had the most significant association with health
      status, with a difference of 9.2 in VAS scores between likely depression and good
      well-being. VAS scores were also significantly lower in patients with high
      diabetes distress and significantly higher in those more frequently conducting
      physical activities. Other psychosocial outcomes were not significantly
      associated with health status. CONCLUSIONS: Likely depression and diabetes
      related distress are negatively associated with health status while frequently
      conducting physical activities are positively associated with health status of
      type 2 diabetes patients aged 18-65 years from 6 districts/counties in Jiangsu
      Provinces. These findings underscore the necessity of undertaking routine
      assessment for depression and diabetes distress and prioritizing interventions on
      promoting regular physical activities in diabetic patients to improve health
      management and achieve better health outcomes.

PMID- 29370175
TI  - Genomic locus modulating corneal thickness in the mouse identifies POU6F2 as a
      potential risk of developing glaucoma.
AB  - Central corneal thickness (CCT) is one of the most heritable ocular traits and it
      is also a phenotypic risk factor for primary open angle glaucoma (POAG). The
      present study uses the BXD Recombinant Inbred (RI) strains to identify novel
      quantitative trait loci (QTLs) modulating CCT in the mouse with the potential of
      identifying a molecular link between CCT and risk of developing POAG. The BXD RI
      strain set was used to define mammalian genomic loci modulating CCT, with a total
      of 818 corneas measured from 61 BXD RI strains (between 60-100 days of age). The
      mice were anesthetized and the eyes were positioned in front of the lens of the
      Phoenix Micron IV Image-Guided OCT system or the Bioptigen OCT system. CCT data
      for each strain was averaged and used to QTLs modulating this phenotype using the
      bioinformatics tools on GeneNetwork (www.genenetwork.org). The candidate genes
      and genomic loci identified in the mouse were then directly compared with the
      summary data from a human POAG genome wide association study (NEIGHBORHOOD) to
      determine if any genomic elements modulating mouse CCT are also risk factors for
      POAG.This analysis revealed one significant QTL on Chr 13 and a suggestive QTL on
      Chr 7. The significant locus on Chr 13 (13 to 19 Mb) was examined further to
      define candidate genes modulating this eye phenotype. For the Chr 13 QTL in the
      mouse, only one gene in the region (Pou6f2) contained nonsynonymous SNPs. Of
      these five nonsynonymous SNPs in Pou6f2, two resulted in changes in the amino
      acid proline which could result in altered secondary structure affecting protein
      function. The 7 Mb region under the mouse Chr 13 peak distributes over 2
      chromosomes in the human: Chr 1 and Chr 7. These genomic loci were examined in
      the NEIGHBORHOOD database to determine if they are potential risk factors for
      human glaucoma identified using meta-data from human GWAS. The top 50 hits all
      resided within one gene (POU6F2), with the highest significance level of p = 10-6
      for SNP rs76319873. POU6F2 is found in retinal ganglion cells and in corneal
      limbal stem cells. To test the effect of POU6F2 on CCT we examined the corneas of
      a Pou6f2-null mice and the corneas were thinner than those of wild-type
      littermates. In addition, these POU6F2 RGCs die early in the DBA/2J model of
      glaucoma than most RGCs. Using a mouse genetic reference panel, we identified a
      transcription factor, Pou6f2, that modulates CCT in the mouse. POU6F2 is also
      found in a subset of retinal ganglion cells and these RGCs are sensitive to
      injury.

PMID- 29370176
TI  - Patterns of sedentary behavior in overweight and moderately obese users of the
      Catalan primary-health care system.
AB  - BACKGROUND AND OBJECTIVES: Prolonged sitting time (ST) has negative consequences
      on health. Changing this behavior is paramount in overweight/obese individuals
      because they are more sedentary than those with normal weight. The aim of the
      study was to establish the pattern of sedentary behavior and its relationship to
      health, socio-demographics, occupation, and education level in Catalan
      overweight/obese individuals. METHODS: A descriptive study was performed at 25
      healthcare centers in Catalonia (Spain) with 464 overweight/moderately obese
      patients, aged25 to 65 years. Exclusion criteria were chronic diseases which
      contraindicated physical activity and language barriers. Face-to-face interviews
      were conducted to collect data on age, gender, educational level, social class,
      and marital status. Main outcome was 'sitting time' (collected by the Marshall
      questionnaire); chronic diseases and anthropometric measurements were registered.
      RESULTS: 464 patients, 58.4% women, mean age 51.9 years (SD 10.1), 76.1% married,
      60% manual workers, and 48.7% had finished secondary education. Daily sitting
      time was 6.2 hours on working days (374 minutes/day, SD: 190), and about 6 hours
      on non-working ones (357 minutes/day, SD: 170). 50% of participants were
      sedentary >=6 hours. The most frequent sedentary activities were:
      working/academic activities around 2 hours (128 minutes, SD: 183), followed by
      watching television, computer use, and commuting. Men sat longer than women (64
      minutes more on working days and 54 minutes on non-working days), and individuals
      with office jobs (91 minutes),those with higher levels of education (42 minutes),
      and younger subjects (25 to 35 years) spent more time sitting. CONCLUSIONS: In
      our study performed in overweight/moderately obese patients the mean sitting time
      was around 6 hours which was mainly spent doing work/academic activities and
      watching television. Men, office workers, individuals with higher education, and
      younger subjects had longer sitting time. Our results may help design
      interventions targeted at these sedentary patients to decrease sitting time.

PMID- 29370177
TI  - Brain and blood metabolite signatures of pathology and progression in Alzheimer
      disease: A targeted metabolomics study.
AB  - BACKGROUND: The metabolic basis of Alzheimer disease (AD) is poorly understood,
      and the relationships between systemic abnormalities in metabolism and AD
      pathogenesis are unclear. Understanding how global perturbations in metabolism
      are related to severity of AD neuropathology and the eventual expression of AD
      symptoms in at-risk individuals is critical to developing effective disease
      modifying treatments. In this study, we undertook parallel metabolomics analyses
      in both the brain and blood to identify systemic correlates of neuropathology and
      their associations with prodromal and preclinical measures of AD progression.
      METHODS AND FINDINGS: Quantitative and targeted metabolomics (Biocrates
      AbsoluteIDQ [identification and quantification] p180) assays were performed on
      brain tissue samples from the autopsy cohort of the Baltimore Longitudinal Study
      of Aging (BLSA) (N = 44, mean age = 81.33, % female = 36.36) from AD (N = 15),
      control (CN; N = 14), and "asymptomatic Alzheimer's disease" (ASYMAD, i.e.,
      individuals with significant AD pathology but no cognitive impairment during
      life; N = 15) participants. Using machine-learning methods, we identified a panel
      of 26 metabolites from two main classes-sphingolipids and glycerophospholipids
      that discriminated AD and CN samples with accuracy, sensitivity, and specificity
      of 83.33%, 86.67%, and 80%, respectively. We then assayed these 26 metabolites in
      serum samples from two well-characterized longitudinal cohorts representing
      prodromal (Alzheimer's Disease Neuroimaging Initiative [ADNI], N = 767, mean age
      = 75.19, % female = 42.63) and preclinical (BLSA) (N = 207, mean age = 78.68, %
      female = 42.63) AD, in which we tested their associations with magnetic resonance
      imaging (MRI) measures of AD-related brain atrophy, cerebrospinal fluid (CSF)
      biomarkers of AD pathology, risk of conversion to incident AD, and trajectories
      of cognitive performance. We developed an integrated blood and brain
      endophenotype score that summarized the relative importance of each metabolite to
      severity of AD pathology and disease progression (Endophenotype Association Score
      in Early Alzheimer's Disease [EASE-AD]). Finally, we mapped the main metabolite
      classes emerging from our analyses to key biological pathways implicated in AD
      pathogenesis. We found that distinct sphingolipid species including sphingomyelin
      (SM) with acyl residue sums C16:0, C18:1, and C16:1 (SM C16:0, SM C18:1, SM
      C16:1) and hydroxysphingomyelin with acyl residue sum C14:1 (SM (OH) C14:1) were
      consistently associated with severity of AD pathology at autopsy and AD
      progression across prodromal and preclinical stages. Higher log-transformed blood
      concentrations of all four sphingolipids in cognitively normal individuals were
      significantly associated with increased risk of future conversion to incident AD:
      SM C16:0 (hazard ratio [HR] = 4.430, 95% confidence interval [CI] = 1.703-11.520,
      p = 0.002), SM C16:1 (HR = 3.455, 95% CI = 1.516-7.873, p = 0.003), SM (OH) C14:1
      (HR = 3.539, 95% CI = 1.373-9.122, p = 0.009), and SM C18:1 (HR = 2.255, 95% CI =
      1.047-4.855, p = 0.038). The sphingolipid species identified map to several
      biologically relevant pathways implicated in AD, including tau phosphorylation,
      amyloid-beta (Abeta) metabolism, calcium homeostasis, acetylcholine biosynthesis,
      and apoptosis. Our study has limitations: the relatively small number of brain
      tissue samples may have limited our power to detect significant associations,
      control for heterogeneity between groups, and replicate our findings in
      independent, autopsy-derived brain samples. CONCLUSIONS: We present a novel
      framework to identify biologically relevant brain and blood metabolites
      associated with disease pathology and progression during the prodromal and
      preclinical stages of AD. Our results show that perturbations in sphingolipid
      metabolism are consistently associated with endophenotypes across preclinical and
      prodromal AD, as well as with AD pathology at autopsy. Sphingolipids may be
      biologically relevant biomarkers for the early detection of AD, and correcting
      perturbations in sphingolipid metabolism may be a plausible and novel therapeutic
      strategy in AD.

PMID- 29370178
TI  - General Practitioner trainers prescribe fewer antibiotics in primary care:
      Evidence from France.
AB  - PURPOSE: Antibiotic prescription is a central public health issue. Overall, 90%
      of antibiotic prescriptions are delivered to patients in ambulatory care, and a
      substantial proportion of these prescriptions could be avoided. General
      Practitioner (GP) trainers are similar to other GPs in terms of sociodemographic
      and medical activities, but they may have different prescription patterns. Our
      aim was to compare the antibiotic prescribing rates between GP trainers and non
      trainers. METHODS: This observational cross-sectional study was conducted on
      administrative data claims from the French National Health Insurance. The
      antibiotic prescribing rate was calculated. The main independent variable was the
      training status of the GPs. Prescribing rates were adjusted for the various GPs'
      characteristics (gender, age, location of the practice, number of visits per GP
      and the case-mix) in a multiple linear regression analysis. RESULTS: Between June
      2014 and July 2015 the prescribing patterns of 860 GPs were analysed, among which
      102 were GP trainers (12%). Over the year 363,580 patients were prescribed an
      antibiotic out of 3,499,248 visits for 1,299,308 patients seen over the year thus
      representing around 27.5% of patients. In the multivariate analyses, being a
      trainer resulted in a significant difference of 6.62 percentage points (IC 95%: [
      8.55; -4.69]; p<0.001) in antibiotic prescriptions comparing to being a non
      trainer, corresponding to a relative reduction of 23.4%. CONCLUSION: These
      findings highlight the role of GP trainers in antibiotic prescriptions. By
      prescribing fewer antibiotics and influencing the next generations of GPs, the
      human and economic burden of antibiotics could be reduced.

PMID- 29370179
TI  - Location, number and factors associated with cerebral microbleeds in an Italian
      British cohort of CADASIL patients.
AB  - BACKGROUND AND PURPOSE: The frequency, clinical correlates, and risk factors of
      cerebral microbleeds (CMB) in Cerebral Autosomal Dominant Arteriopathy with
      Subcortical Infarcts and Leukoencephalopathy (CADASIL) are still poorly known. We
      aimed at determining the location and number of CMB and their relationship with
      clinical manifestations, vascular risk factors, drugs, and other neuroimaging
      features in CADASIL patients. METHODS: We collected clinical data by means of a
      structured proforma and centrally evaluated CMB on magnetic resonance gradient
      echo sequences applying the Microbleed Anatomical Rating Scale in CADASIL
      patients seen in 2 referral centers in Italy and United Kingdom. RESULTS: We
      evaluated 125 patients. CMB were present in 34% of patients and their presence
      was strongly influenced by the age. Twenty-nine percent of the patients had CMB
      in deep subcortical location, 22% in a lobar location, and 18% in infratentorial
      regions. After adjustment for age, factors significantly associated with a higher
      total number of CMB were hemorrhagic stroke, dementia, urge incontinence, and
      statins use (this latter not confirmed by multivariate analysis). Infratentorial
      and deep CMB were associated with dementia and urge incontinence, lobar CMB with
      hemorrhagic stroke, dementia, and statins use. Unexpectedly, patients with
      migraine, with or without aura, had a lower total, deep, and lobar number of CMB
      than patients without migraine. DISCUSSION: CMB formation in CADASIL seems to
      increase with age. History of hemorrhagic stroke, dementia, urge incontinence,
      and statins use are associated with a higher number of CMB. However, these
      findings need to be confirmed by longitudinal studies.

PMID- 29370180
TI  - Acute kidney injury in cats and dogs: A proportional meta-analysis of case series
      studies.
AB  - INTRODUCTION: Risk of mortality in the setting of acute kidney injury (AKI) in
      cats and dogs remains unclear. OBJECTIVES: To evaluate the incidence of mortality
      in cats and dogs with AKI based on etiology (i.e. infectious versus non
      infectious; receiving dialysis versus conservative treatment). MATERIALS AND
      METHODS: Ovid Medline, EMBASE, and LILACS were searched up to July 2016. Articles
      were deemed eligible if they were case series studies evaluating the incidence of
      all-cause mortality in cats and dogs with AKI, regardless of etiology or the
      nature of treatment. RESULTS: Eighteen case series involving 1,201animalsproved
      eligible. The pooled proportions for overall mortality were: cats53.1% [95% CI
      0.475, 0.586; I2 = 11,9%, p = 0.3352]; dogs 45.0% [95% CI 0.33, 0.58; I2 = 91.5%,
      P < 0.0001]. A non-significant increase in overall mortality risk was found among
      dialysed animals relative to those managed with conservative treatment,
      independent of animal type and the etiology of their AKI. The pooled proportions
      for overall mortality according to etiology, regardless of treatment type, were:
      AKI due infectious etiology for cats and dogs, 19.2% [95% CI 0.134, 0.258; I2 =
      37.7%, P = 0.0982]; AKI due non-infectious etiology for cats and dogs, 59.9% [95%
      CI 0.532, 0.663; I2 = 51.0%, P = 0.0211]. CONCLUSION: Our findings suggest higher
      rates of overall mortality in cats and dogs with AKI due to non-infectious
      etiologies relative to infectious etiologies, and showed non-significant
      differences in terms of higher rates associated with dialysis compared to
      conservative management. Further investigations regarding optimal time to
      initiate dialysis and the development of clinical models to prognosticate the
      course of disease and guide optimal treatment initiation for less severe cases of
      AKI in cats and dogs is warranted.

PMID- 29370181
TI  - Inferring hidden causal relations between pathway members using reduced Google
      matrix of directed biological networks.
AB  - Signaling pathways represent parts of the global biological molecular network
      which connects them into a seamless whole through complex direct and indirect
      (hidden) crosstalk whose structure can change during development or in
      pathological conditions. We suggest a novel methodology, called Googlomics, for
      the structural analysis of directed biological networks using spectral analysis
      of their Google matrices, using parallels with quantum scattering theory,
      developed for nuclear and mesoscopic physics and quantum chaos. We introduce
      analytical "reduced Google matrix" method for the analysis of biological network
      structure. The method allows inferring hidden causal relations between the
      members of a signaling pathway or a functionally related group of genes. We
      investigate how the structure of hidden causal relations can be reprogrammed as a
      result of changes in the transcriptional network layer during cancerogenesis. The
      suggested Googlomics approach rigorously characterizes complex systemic changes
      in the wiring of large causal biological networks in a computationally efficient
      way.

PMID- 29370182
TI  - Correlation of pathological complete response with survival after neoadjuvant
      chemotherapy in gastric or gastroesophageal junction cancer treated with radical
      surgery: A meta-analysis.
AB  - BACKGROUND: Neoadjuvant chemotherapy before radical gastrectomy is preferred for
      locally advanced gastric cancer. To avoid the problematic use of pTNM for
      patients after neoadjuvant chemotherapy, the Union for International Cancer
      Control (UICC) and the American Joint Committee on Cancer (AJCC) gastric cancer
      TNM staging system (8th edition) added ypTNM for the first time. But patients
      achieving pathological complete response were not covered by the new ypTNM
      staging system. To investigate whether pathological complete response is
      associated with better outcome in gastric cancer, as was reported in rectal,
      breast and bladder cancer. METHODS: We systematically searched the databases of
      PubMed, EMBASE, Web of Science and Cochrane Collaboration's Central register of
      controlled trials from January 1988 to April 2015 for publications which reported
      outcomes of patients with and without pathological complete response (pCR)
      (pT0N0M0) to investigate whether pCR after neoadjuvant chemotherapy in gastric or
      gastroesophageal junction (GEJ) treated with radical surgery is associated with
      better survival. The primary outcome was overall survival (OS). The secondary
      outcome was disease-free survival (DFS). Both were measured with a relative risk
      (RR). A meta-analysis was performed using the fixed effects model. Forest plots
      and the Q test was used to evaluate overall heterogeneity for OS and DFS.
      RESULTS: A total of seven trials, 1143 patients were included and analyzed after
      neoadjuvant chemotherapy and radical surgery with no other preoperative
      treatment. The average rate of pCR was 6.74% (range: 3%-15%). The RR of patients
      who achieved pCR in the primary tumor and lymph nodes is 0.5 (95% confidence
      interval [CI], 0.25-0.98; p = 0.04), 0.34 (95% CI, 0.21-0.55; p<0.0001) and 0.44
      (95% CI, 0.30-0.63; p<0.0001) for one-year-OS, three-year-OS and five-year-OS,
      respectively. The summary RR for three-year-DFS was 0.43 (95% CI, 0.25-0.72; p =
      0.002). CONCLUSION: Patients with resectable gastric or GEJ cancer who achieved
      pCR after neoadjuvant chemotherapy can gain a better outcome than patients
      without pCR.

PMID- 29370183
TI  - Oral anticoagulant re-initiation following intracerebral hemorrhage in non
      valvular atrial fibrillation: Global survey of the practices of neurologists,
      neurosurgeons and thrombosis experts.
AB  - BACKGROUND: While oral anticoagulants (OACs) are highly effective for ischemic
      stroke prevention in atrial fibrillation, intracerebral hemorrhage (ICH) remains
      the most feared complication of OAC. Clinical controversy remains regarding OAC
      resumption and its timing for ICH survivors with atrial fibrillation because the
      balance between risks and benefits has not been investigated in randomized
      trials. AIMS/HYPOTHESIS: To survey the practice of stroke neurologists,
      thrombosis experts and neurosurgeons on OAC re-initiation following OAC
      associated ICH. METHODS: An online survey was distributed to members of the
      International Society for Thrombosis and Haemostasis, Canadian Stroke Consortium,
      NAVIGATE-ESUS trial investigators (Clinicatrials.gov identifier NCT02313909) and
      American Association of Neurological Surgeons. Demographic factors and 11
      clinical scenarios were included. RESULTS: Two hundred twenty-eight participants
      from 38 countries completed the survey. Majority of participants were affiliated
      with academic centers, and >20% managed more than 15 OAC-associated ICH
      patients/year. Proportion of respondents suggesting OAC anticoagulant resumption
      varied from 30% (for cerebral amyloid angiopathy) to 98% (for traumatic ICH).
      Within this group, there was wide distribution in response for timing of
      resumption: 21.4% preferred to re-start OACs after 1-3 weeks of incident ICH,
      while 25.3% opted to start after 1-3 months. Neurosurgery respondents preferred
      earlier OAC resumption compared to stroke neurologists or thrombosis experts in 5
      scenarios (p<0.05 by Kendall's tau). CONCLUSIONS: Wide variations in current
      practice exist among management of OAC-associated ICH, with decisions influenced
      by patient- and provider-related factors. As these variations likely reflect the
      lack of high quality evidence, randomized trials are direly needed in this
      population.

PMID- 29370184
TI  - Taking cohesin and condensin in context.
AB  - Structural maintenance of chromosome (SMC) protein complexes, including cohesin
      and condensin, are increasingly being recognized for their important role in
      cancer and development, making it critical that we understand how these
      evolutionarily conserved multi-subunit protein complexes associate with and
      organize the genome. We review adaptor proteins for SMC complexes and how these
      adaptors may capture SMC complexes following loop extrusion to provide a
      framework for chromosome organization.

PMID- 29370185
TI  - Adjuvanting influenza hemagglutinin vaccine with a human pulmonary surfactant
      mimicking synthetic compound SF-10 induces local and systemic cell-mediated
      immunity in mice.
AB  - We reported previously that intranasal instillation of a synthetic human
      pulmonary surfactant with a carboxy vinyl polymer as a viscosity improver, named
      SF-10, shows potent adjuvanticity for humoral immunity in mice and cynomolgus
      monkeys. SF-10 effectively induces influenza hemagglutinin vaccine (HAv)-specific
      IgA in nasal and lung washes and IgG in sera with their neutralizing activities.
      Since CD8+ T cell-mediated protection is an important requirement for adaptive
      immunity, we investigated in this study the effects of SF-10 with antigen on
      local and systemic cell-mediated immunity. Nasal instillation of ovalbumin, a
      model antigen, combined with SF-10 efficiently delivered antigen to mucosal
      dendritic and epithelial cells and promoted cross-presentation in antigen
      presenting cells, yielding a high percentage of ovalbumin-specific cytotoxic T
      lymphocytes in the nasal mucosa, compared with ovalbumin alone. Nasal
      immunization of HAv-SF-10 also induced HAv-specific cytotoxic T lymphocytes and
      upregulated granzyme B expression in splenic CD8+ T cells with their high
      cytotoxicity against target cells pulsed with HA peptide. Furthermore, nasal
      vaccination of HAv-SF-10 significantly induced higher cytotoxic T lymphocytes
      mediated cytotoxicity in the lungs and cervical lymph nodes in the early phase of
      influenza virus infection compared with HAv alone. Protective immunity induced by
      HAv-SF-10 against lethal influenza virus infection was partially and
      predominantly suppressed after depletion of CD8+ and CD4+ T cells (induced by
      intraperitoneal injection of the corresponding antibodies), respectively,
      suggesting that CD4+ T cells predominantly and CD8+ T cells partially contribute
      to the protective immunity in the advanced stage of influenza virus infection.
      These results suggest that SF-10 promotes effective antigen delivery to antigen
      presenting cells, activates CD8+ T cells via cross-presentation, and induces cell
      mediated immune responses against antigen.

PMID- 29370186
TI  - Evaluation of limited irrigation strategies to improve water use efficiency and
      wheat yield in the North China Plain.
AB  - The North China Plain is one of the most important grain production regions in
      China, but is facing serious water shortages. To achieve a balance between water
      use and the need for food self-sufficiency, new water efficient irrigation
      strategies need to be developed that balance water use with farmer net return.
      The Crop Environment Resource Synthesis Wheat (CERES-Wheat model) was calibrated
      and evaluated with two years of data which consisted of 3-4 irrigation
      treatments, and the model was used to investigate long-term winter wheat
      productivity and water use from irrigation management in the North China Plain.
      The calibrated model simulated accurately above-ground biomass, grain yield and
      evapotranspiration of winter wheat in response to irrigation management. The
      calibrated model was then run using weather data from 1994-2016 in order to
      evaluate different irrigation strategies. The simulated results using historical
      weather data showed that grain yield and water use was sensitive to different
      irrigation strategies including amounts and dates of irrigation applications. The
      model simulated the highest yield when irrigation was applied at jointing (T9) in
      normal and dry rainfall years, and gave the highest simulated yields for
      irrigation at double ridge (T8) in wet years. A single simulated irrigation at
      jointing (T9) produced yields that were 88% compared to using a double irrigation
      treatment at T1 and T9 in wet years, 86% of that in normal years, and 91% of that
      in dry years. A single irrigation at jointing or double ridge produced higher
      water use efficiency because it obtained higher evapotranspiration. The simulated
      farmer irrigation practices produced the highest yield and net income. When the
      cost of water was taken into account, limited irrigation was found to be more
      profitable based on assumptions about future water costs. In order to increase
      farmer income, a subsidy will likely be needed to compensate farmers for yield
      reductions due to water savings. These results showed that there is a cost to the
      farmer for water conservation, but limiting irrigation to a single irrigation at
      jointing would minimize impact on farmer net return in North China Plain.

PMID- 29370187
TI  - Impacts of the Deepwater Horizon oil spill evaluated using an end-to-end
      ecosystem model.
AB  - We use a spatially explicit biogeochemical end-to-end ecosystem model, Atlantis,
      to simulate impacts from the Deepwater Horizon oil spill and subsequent recovery
      of fish guilds. Dose-response relationships with expected oil concentrations were
      utilized to estimate the impact on fish growth and mortality rates. We also
      examine the effects of fisheries closures and impacts on recruitment. We validate
      predictions of the model by comparing population trends and age structure before
      and after the oil spill with fisheries independent data. The model suggests that
      recruitment effects and fishery closures had little influence on biomass
      dynamics. However, at the assumed level of oil concentrations and toxicity,
      impacts on fish mortality and growth rates were large and commensurate with
      observations. Sensitivity analysis suggests the biomass of large reef fish
      decreased by 25% to 50% in areas most affected by the spill, and biomass of large
      demersal fish decreased even more, by 40% to 70%. Impacts on reef and demersal
      forage caused starvation mortality in predators and increased reliance on pelagic
      forage. Impacts on the food web translated effects of the spill far away from the
      oiled area. Effects on age structure suggest possible delayed impacts on fishery
      yields. Recovery of high-turnover populations generally is predicted to occur
      within 10 years, but some slower-growing populations may take 30+ years to fully
      recover.

PMID- 29370188
TI  - Shedding light on the Early Pleistocene of TD6 (Gran Dolina, Atapuerca, Spain):
      The technological sequence and occupational inferences.
AB  - This paper aims to update the information available on the lithic assemblage from
      the entire sequence of TD6 now that the most recent excavations have been
      completed, and to explore possible changes in both occupational patterns and
      technological strategies evidenced in the unit. This is the first study to
      analyse the entire TD6 sequence, including subunits TD6.3 and TD6.1, which have
      never been studied, along with the better-known TD6.2 Homo antecessor-bearing
      subunit. We also present an analysis of several lithic refits found in TD6, as
      well as certain technical features that may help characterise the hominin
      occupations. The archaeo-palaeontological record from TD6 consists of 9,452
      faunal remains, 443 coprolites, 1,046 lithic pieces, 170 hominin remains and 91
      Celtis seeds. The characteristics of this record seem to indicate two main stages
      of occupation. In the oldest subunit, TD6.3, the lithic assemblage points to the
      light and limited hominin occupation of the cave, which does, however, grow over
      the course of the level. In contrast, the lithic assemblages from TD6.2 and TD6.1
      are rich and varied, which may reflect Gran Dolina cave's establishment as a
      landmark in the region. Despite the occupational differences between the
      lowermost subunit and the rest of the deposit, technologically the TD6 lithic
      assemblage is extremely homogeneous throughout. In addition, the composition and
      spatial distribution of the 12 groups of lithic refits found in unit TD6, as well
      as the in situ nature of the assemblage demonstrate the high degree of
      preservation at the site. This may help clarify the nature of the Early
      Pleistocene hominin occupations of TD6, and raise reasonable doubt about the
      latest interpretations that support the ex situ character of the assemblage as a
      whole.

PMID- 29370190
TI  - Classification of rare land cover types: Distinguishing annual and perennial
      crops in an agricultural catchment in South Korea.
AB  - Many environmental data are inherently imbalanced, with some majority land use
      and land cover types dominating over rare ones. In cultivated ecosystems minority
      classes are often the target as they might indicate a beginning land use change.
      Most standard classifiers perform best on a balanced distribution of classes, and
      fail to detect minority classes. We used the synthetic minority oversampling
      technique (smote) with Random Forest to classify land cover classes in a small
      agricultural catchment in South Korea using modis time series. This area faces a
      major soil erosion problem and policy measures encourage farmers to replace
      annual by perennial crops to mitigate this issue. Our major goal was therefore to
      improve the classification performance on annual and perennial crops. We compared
      four different classification scenarios on original imbalanced and synthetically
      oversampled balanced data to quantify the effect of smote on classification
      performance. smote substantially increased the true positive rate of all
      oversampled minority classes. However, the performance on minor classes remained
      lower than on the majority class. We attribute this result to a class overlap
      already present in the original data set that is not resolved by smote. Our
      results show that resampling algorithms could help to derive more accurate land
      use and land cover maps from freely available data. These maps can be used to
      provide information on the distribution of land use classes in heterogeneous
      agricultural areas and could potentially benefit decision making.

PMID- 29370189
TI  - A monomethyl auristatin E-conjugated antibody to guanylyl cyclase C is cytotoxic
      to target-expressing cells in vitro and in vivo.
AB  - Guanylyl cyclase C (GCC) is a cell-surface protein that is expressed by normal
      intestinal epithelial cells, more than 95% of metastatic colorectal cancers
      (mCRC), and the majority of gastric and pancreatic cancers. Due to strict apical
      localization, systemically delivered GCC-targeting agents should not reach GCC in
      normal intestinal tissue, while accessing antigen in tumor. We generated an
      investigational antibody-drug conjugate (TAK-264, formerly MLN0264) comprising a
      fully human anti-GCC monoclonal antibody conjugated to monomethyl auristatin E
      via a protease-cleavable peptide linker. TAK-264 specifically bound, was
      internalized by, and killed GCC-expressing cells in vitro in an antigen-density
      dependent manner. In GCC-expressing xenograft models with similar GCC expression
      levels/patterns observed in human mCRC samples, TAK-264 induced cell death,
      leading to tumor regressions and long-term tumor growth inhibition. TAK-264
      antitumor activity was generally antigen-density-dependent, although some GCC
      expressing tumors were refractory to TAK-264-targeted high local concentrations
      of payload. These data support further evaluation of TAK-264 in the treatment of
      GCC-expressing tumors.

PMID- 29370191
TI  - Completeness and reliability of mortality data in Viet Nam: Implications for the
      national routine health management information system.
AB  - BACKGROUND: Mortality statistics form a crucial component of national Health
      Management Information Systems (HMIS). However, there are limitations in the
      availability and quality of mortality data at national level in Viet Nam. This
      study assessed the completeness of recorded deaths and the reliability of
      recorded causes of death (COD) in the A6 death registers in the national routine
      HMIS in Viet Nam. METHODOLOGY AND FINDINGS: 1477 identified deaths in 2014 were
      reviewed in two provinces. A capture-recapture method was applied to assess the
      completeness of the A6 death registers. 1365 household verbal autopsy (VA)
      interviews were successfully conducted, and these were reviewed by physicians who
      assigned multiple and underlying cause of death (UCOD). These UCODs from VA were
      then compared with the CODs recorded in the A6 death registers, using kappa
      scores to assess the reliability of the A6 death register diagnoses. The overall
      completeness of the A6 death registers in the two provinces was 89.3% (95%CI:
      87.8-90.8). No COD recorded in the A6 death registers demonstrated good
      reliability. There is very low reliability in recording of cardiovascular deaths
      (kappa for stroke = 0.47 and kappa for ischaemic heart diseases = 0.42) and
      diabetes (kappa = 0.33). The reporting of deaths due to road traffic accidents,
      HIV and some cancers are at a moderate level of reliability with kappa scores
      ranging between 0.57-0.69 (p<0.01). VA methods identify more specific COD than
      the A6 death registers, and also allow identification of multiple CODs.
      CONCLUSIONS: The study results suggest that data completeness in HMIS A6 death
      registers in the study sample of communes was relatively high (nearly 90%), but
      triangulation with death records from other sources would improve the
      completeness of this system. Further, there is an urgent need to enhance the
      reliability of COD recorded in the A6 death registers, for which VA methods could
      be effective. Focussed consultation among stakeholders is needed to develop a
      suitable mechanism and process for integrating VA methods into the national
      routine HMIS A6 death registers in Viet Nam.

PMID- 29370192
TI  - Development and evaluation of Chitosan nanoparticles based dry powder inhalation
      formulations of Prothionamide.
AB  - Prothionamide (PTH), a second line antitubercular drug is used to administer in
      conventional oral route. However, its unpredictable absorption and frequent
      administration limit its use. An alternate approach was thought of administering
      PTH through pulmonary route in a form of nanoparticles, which can sustain the
      release for several hours in lungs. Chitosan, a bio-degradable polymer was used
      to coat PTH and further freeze dried to prepare dry powder inhaler (DPI) with
      aerodynamic particle size of 1.76MUm. In vitro release study showed initial burst
      release followed by sustained release up to 96.91% in 24h. In vitro release
      further correlated with in vivo study. Prepared DPI maintained the PTH
      concentration above MIC for more than 12h after single dose administration and
      increased the PTH residency in the lungs tissue more than 24h. Animal study also
      revealed the reduction of dose in pulmonary administration, which will improve
      the management of tuberculosis.

PMID- 29370193
TI  - Inhibition of alpha-glucosidase, alpha-amylase, and aldose reductase by potato
      polyphenolic compounds.
AB  - Diabetes mellitus is a chronic disease that is becoming a serious global health
      problem. Diabetes has been considered to be one of the major risks of cataract
      and retinopathy. Synthetic and natural product inhibitors of carbohydrate
      degrading enzymes are able to reduce type 2 diabetes and its complications. For a
      long time, potatoes have been portrayed as unhealthy for diabetic patients by
      some nutritionist due to their high starch content. However, purple and red
      potato cultivars have received considerable attention from consumers because they
      have high levels of polyphenolic compounds that have potent antioxidant
      activities. In this study, we screened the total phenolics (TP) and total
      anthocyanins (TA) and analyzed the phenolic and anthocyanin compounds in selected
      potato cultivars and advanced selections with distinct flesh colors (purple, red,
      yellow and white). Purple and red potato cultivars had higher levels of TP and TA
      than tubers with other flesh colors. Chlorogenic acid is the predominant phenolic
      acid, and major anthocyanin is composed of the derivatives of petunidin,
      peonidin, malvidin and pelargonidin. We tested the potential inhibitory effect of
      potato extracts on the activities of alpha-amylase and alpha-glucosidase, which
      were targeted to develop antidiabetic therapeutic agents. We also measured
      inhibitory effect of potato extracts on aldose reductase (AR) which is a key
      enzyme that has been a major drug target for the development of therapies to
      treat diabetic complications. Purple flesh tubers extract showed the most
      effective inhibition of alpha-amylase, alpha-glucosidase, and aldose reductase
      with IC50 values 25, 42, and 32 MUg/ml, respectively. Kinetic studies showed that
      anthocyanins are noncompetitive inhibitors of these enzymes, whereas phenolic
      acids behaved as mixed inhibitors for alpha-amylase and alpha-glucosidase and
      noncompetitive inhibitors for AR. This study supports the development of a
      positive and healthful image of potatoes, which is an important issue for
      consumers.

PMID- 29370194
TI  - The role of spatial heterogeneity in the evolution of local and global infections
      of viruses.
AB  - Viruses have two modes spread in a host body, one is to release infectious
      particles from infected cells (global infection) and the other is to infect
      directly from an infected cell to an adjacent cell (local infection). Since the
      mode of spread affects the evolution of life history traits, such as virulence,
      it is important to reveal what level of global and local infection is selected.
      Previous studies of the evolution of global and local infection have paid little
      attention to its dependency on the measures of spatial configuration. Here we
      show the evolutionarily stable proportion of global and local infection, and how
      it depends on the distribution of target cells. Using an epidemic model on a
      regular lattice, we consider the infection dynamics by pair approximation and
      check the evolutionarily stable strategy. We also conduct the Monte-Carlo
      simulation to observe evolutionary dynamics. We show that a higher local
      infection is selected as target cells become clustered. Surprisingly, the
      selected strategy depends not only on the degree of clustering but also the
      abundance of target cells per se.

PMID- 29370195
TI  - Reliability and reproducibility of disc-foveal angle measurements by non
      mydriatic fundus photography.
AB  - PURPOSE: Abnormal torsion could be associated with cyclovertical strabismus, but
      torsion measurements are not reliable in children. To assess an objective fundus
      torsion evaluation in a paediatric population, we used Non-Mydriatic Fundus
      photography (NMFP) in healthy and cyclovertical strabismus patients to evaluate
      the disc-foveal angle over time and observers. METHODS: We used a retrospective
      set of NMFP including 24 A or V-pattern strabismus and 27 age-matched normal
      children (mean age 6.4 and 6.7 years respectively), taken during 2 distinct
      follow-up consultations (separated by 251 and 479 days respectively). Each disc
      foveal angle measurement (from which the ocular torsion can be assessed) was
      performed by 5 different observers, using graphical software and based on
      reproducible fundus anatomical marks. Statistical analysis was performed with a
      multivariate ANOVA using group, time and observers as factors, in addition to
      intraclass coefficient correlation (ICC) to assess measurement reproducibility.
      RESULTS: A significant difference of disc-foveal angle measures was observed
      between groups (p<0,001): 18.73 degrees  (SD = 6.42), -3,25 degrees  (SD = 5.51)
      and 6,89 degrees  (SD = 4,41) respectively for V-pattern, A- pattern and normal
      subjects. Neither observers (F = 0,2028 p = 0,9369) nor time between 1st and 2nd
      NMFP (F = 0,6312 p = 0,4271) seem to influence the measure of disc-foveal angle.
      The evaluation of disc-foveal angle was very reproducible between observers
      (ICC>0,97). CONCLUSION: Abnormal amount of objective torsion could be associated
      with alphabet-pattern strabismus. Disc-foveal angle evaluation by NMFP in a
      children population appears as a non-invasive, reliable and reproducible method.

PMID- 29370196
TI  - Lower pre-ART intra-participant HIV-1 pol diversity may not be associated with
      virologic failure in adults.
AB  - BACKGROUND: Identifying pre-ART factors associated with the emergence of HIV-1
      drug resistance is critical for optimizing strategies to prevent virologic
      failure. A previous study reported that lower pre-ART HIV-1 pol diversity was
      associated with higher risk of virologic failure in HIV-1-infected children. To
      investigate this association in adults, we measured HIV-1 diversity with deep
      sequencing in pre-ART samples from adults with well-characterized virologic
      outcomes in a study (A5142) of initial ART conducted by the AIDS Clinical Trials
      Group (ACTG). METHODS: We identified 22 cases in ACTG A5142 who experienced
      virologic failure with drug resistance mutations in RT and 44 matched controls
      who did not experience virologic failure. cDNA was synthesized from plasma HIV-1
      RNA. Each cDNA molecule was tagged with a unique primer ID and RT codons 41-103
      were amplified and deep sequenced. Sequences with the same tag were aligned and a
      consensus was generated to reduce PCR and sequencing errors. Diversity was
      calculated by measuring average pairwise distance (APD) of the consensus
      sequences. An exact conditional logistic regression model with percent APD as the
      risk factor estimated the odds ratio for VF and the corresponding 95% confidence
      interval. RESULTS: Consensus single-genome sequences and diversity estimates of
      pol were obtained for pre-ART samples from 21 cases and 42 controls. The median
      (IQR) pre-ART percent APD was 0.71 (0.31-1.13) in cases and 0.58 (0.32-0.94) in
      controls. A possible trend was found for higher diversity being associated with
      greater risk of virologic failure in adults (OR = 2.2 per one percent APD
      increase, 95% CI = [0.8, 7.2]; p = 0.15). CONCLUSIONS: This study in adults
      suggests there is a positive association between higher pre-ART pol diversity and
      the risk of virologic failure in adults rather than an inverse relationship
      reported in children.

PMID- 29370197
TI  - Changes in opiate and stimulant use through 10 years: The role of contextual
      factors, mental health disorders and psychosocial factors in a prospective SUD
      treatment cohort study.
AB  - AIM: To examine temporal changes in opiate and stimulant use among patients in
      substance abuse treatment over a ten-year observation period and to explore the
      role of contextual factors, mental health disorders and psychosocial factors on
      these changes. METHODS: A cohort of 481 patients was prospectively interviewed at
      admission to treatment and after 1, 2, 7 and 10 years. The sample was recruited
      from 20 facilities in the Greater Oslo region, Norway. RESULTS: The majority of
      patients were poly-drug users and 80% had used both opiates and stimulants the
      last 30 days prior to treatment admission. Last-month use of heroin, other
      opiates, cocaine and amphetamines declined from 80% to 34% at the end of the
      observation period. The most substantial reduction was observed between baseline
      and one-year follow-up. Use of heroin decreased the most from 62% to 16% after 10
      years (a reduction of 74%), and the reduction continued from one-year follow-up
      throughout the observation period. The most important multivariate risk factors
      for sustained use of these drugs were male gender, having one or both biological
      parents with severe alcohol or drug problems, having an antisocial personality
      disorder, and living together with a person who abuses alcohol or drugs.
      Employment was associated with reduced risk of drug use at 7-year follow-up.
      CONCLUSIONS: There was a substantial reduction in opiate and stimulant use from
      baseline to all follow-up assessments, most greatly for heroin. Findings
      regarding sustained use could suggest familial transmission and the challenges of
      preventive strategies and treatment efforts in an intergenerational context. Co
      occurrence between drug abuse and mental health problems highlights the need of
      highly specialized competence in SUD treatment.

PMID- 29370198
TI  - Gender differences in emotion perception and self-reported emotional
      intelligence: A test of the emotion sensitivity hypothesis.
AB  - Previous meta-analyses and reviews on gender differences in emotion recognition
      have shown a small to moderate female advantage. However, inconsistent evidence
      from recent studies has raised questions regarding the implications of different
      methodologies, stimuli, and samples. In the present research based on a community
      sample of more than 5000 participants, we tested the emotional sensitivity
      hypothesis, stating that women are more sensitive to perceive subtle, i.e. low
      intense or ambiguous, emotion cues. In addition, we included a self-report
      emotional intelligence test in order to examine any discrepancy between self
      perceptions and actual performance for both men and women. We used a wide range
      of stimuli and models, displaying six different emotions at two different
      intensity levels. In order to better tap sensitivity for subtle emotion cues, we
      did not use a forced choice format, but rather intensity measures of different
      emotions. We found no support for the emotional sensitivity account, as both
      genders rated the target emotions as similarly intense at both levels of stimulus
      intensity. Men, however, more strongly perceived non-target emotions to be
      present than women. In addition, we also found that the lower scores of men in
      self-reported EI was not related to their actual perception of target emotions,
      but it was to the perception of non-target emotions.

PMID- 29370199
TI  - Meta-analysis: High-dose vs. low-dose metronidazole-containing therapies for
      Helicobacter pylori eradication treatment.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of high dose of
      metronidazole in the treatment of Helicobacter pylori (H. pylori) infection.
      METHODS: Studies were identified from databases (Pubmed, Embase, Cochrane
      Library, ClinicalTrials.gov) searched from January 1990 to September 2017 using a
      battery of keywords. We included randomized controlled trials (RCTs) of H. pylori
      treatment comparing the high-dose and low-dose metronidazole-containing therapies
      (high-dose and low-dose therapies). Two reviewers independently selected studies,
      extracted relevant data and assessed study quality. A meta-analysis was performed
      by using Review Manager 5.3. Dichotomous data were pooled to obtain the relative
      risk (RR) of the eradication rate, with 95% confidence intervals (CIs). RESULTS:
      Four randomized controlled trials, a total of 612 patients with a diagnosis of H.
      pylori infection were included. Overall the meta-analysis showed that both high
      dose and low-dose therapies achieved similar efficacy of intention-to-treat (ITT)
      eradication rate 82% vs. 76%, RR 1.12 (95%CI: 0.96 to 1.30), P = 0.15, and
      adherence 94% vs. 94%, RR 1.00 (95%CI: 0.97 to 1.04), P = 0.81, but side effects
      were more likely in high-dose therapies [32% vs. 17%, RR 1.84 (95%CI: 1.17 to
      2.88), P = 0.008]. In subgroup analysis, increasing the dose of metronidazole
      enhanced eradication rates in areas with high metronidazole resistance [74% vs
      52%, RR 1.40 (95%CI: 1.08 to 1.82), P = 0.01] and in individuals with
      metronidazole-resistant strains [71% vs. 46%, RR 1.50 (95%CI: 1.02 to 2.19), P =
      0.04]. CONCLUSIONS: Both high-dose and low-dose therapies can achieve similar
      eradication rates and adherence and generally low-dose therapies cause fewer side
      effects. In populations with high metronidazole resistance, high dose of
      metronidazole can increase the eradication rates of H. pylori infection.

PMID- 29370200
TI  - A systematic approach to analyze the social determinants of cardiovascular
      disease.
AB  - Cardiovascular diseases are the leading cause of human mortality worldwide. Among
      the many factors associated with the etiology, incidence, and evolution of such
      diseases; social and environmental issues constitute an important and often
      overlooked component. Understanding to a greater extent the scope to which such
      social determinants of cardiovascular diseases (SDCVD) occur as well as the
      connections among them would be useful for public health policy making. Here, we
      will explore the historical trends and associations among the main SDCVD in the
      published literature. Our aim will be finding meaningful relations among those
      that will help us to have an integrated view on this complex phenomenon by
      providing historical context and a relational framework. To uncover such
      relations, we used a data mining approach to the current literature, followed by
      network analysis of the interrelationships discovered. To this end, we
      systematically mined the PubMed/MEDLINE database for references of published
      studies on the subject, as outlined by the World Health Organization's framework
      on social determinants of health. The analyzed structured corpus consisted in
      circa 1190 articles categorized by means of the Medical Subheadings (MeSH)
      content-descriptor. The use of data analytics techniques allowed us to find a
      number of non-trivial connections among SDCVDs. Such relations may be relevant to
      get a deeper understanding of the social and environmental issues associated with
      cardiovascular disease and are often overlooked by traditional literature survey
      approaches, such as systematic reviews and meta-analyses.

PMID- 29370201
TI  - Network evolution model for supply chain with manufactures as the core.
AB  - Building evolution model of supply chain networks could be helpful to understand
      its development law. However, specific characteristics and attributes of real
      supply chains are often neglected in existing evolution models. This work
      proposes a new evolution model of supply chain with manufactures as the core,
      based on external market demand and internal competition-cooperation. The
      evolution model assumes the external market environment is relatively stable,
      considers several factors, including specific topology of supply chain, external
      market demand, ecological growth and flow conservation. The simulation results
      suggest that the networks evolved by our model have similar structures as real
      supply chains. Meanwhile, the influences of external market demand and internal
      competition-cooperation to network evolution are analyzed. Additionally, 38
      benchmark data sets are applied to validate the rationality of our evolution
      model, in which, nine manufacturing supply chains match the features of the
      networks constructed by our model.

PMID- 29370202
TI  - Step-by-step variability of swing phase trajectory area during steady state
      walking at a range of speeds.
AB  - BACKGROUND: Step kinematic variability has been characterized during gait using
      spatial and temporal kinematic characteristics. However, people can adopt
      different trajectory paths both between individuals and even within individuals
      at different speeds. Single point measures such as minimum toe clearance (MTC)
      and step length (SL) do not necessarily account for the multiple paths that the
      foot may take during the swing phase to reach the same foot fall endpoint. The
      purpose of this study was to test a step-by-step foot trajectory area (SBS-FTA)
      variability measure that is able to characterize sagittal plane foot trajectories
      of varying areas, and compare this measure against MTC and SL variability at
      different speeds. We hypothesize that the SBS-FTA variability would demonstrate
      increased variability with speed. Second, we hypothesize that SBS-FTA would have
      a stronger curvilinear fit compared with the CV and SD of SL and MTC. Third, we
      hypothesize SBS-FTA would be more responsive to change in the foot trajectory at
      a given speed compared to SL and MTC. Fourth, SBS-FTA variability would not
      strongly co-vary with SL and MTC variability measures since it represents a
      different construct related to foot trajectory area variability. METHODS: We
      studied 15 nonimpaired individuals during walking at progressively faster speeds.
      We calculated SL, MTC, and SBS-FTA area. RESULTS: SBS-FTA variability increased
      with speed, had a stronger curvilinear fit compared with the CV and SD of SL and
      MTC, was more responsive at a given speed, and did not strongly co-vary with SL
      and MTC variability measures. CONCLUSION: SBS foot trajectory area variability
      was sensitive to change with faster speeds, captured a relationship that the
      majority of the other measures did not demonstrate, and did not co-vary strongly
      with other measures that are also components of the trajectory.

PMID- 29370203
TI  - Modelling multi-rotor UAVs swarm deployment using virtual pheromones.
AB  - In this work, a swarm behaviour for multi-rotor Unmanned Aerial Vehicles (UAVs)
      deployment will be presented. The main contribution of this behaviour is the use
      of a virtual device for quantitative sematectonic stigmergy providing more
      adaptable behaviours in complex environments. It is a fault tolerant highly
      robust behaviour that does not require prior information of the area to be
      covered, or to assume the existence of any kind of information signals (GPS,
      mobile communication networks ...), taking into account the specific features of
      UAVs. This behaviour will be oriented towards emergency tasks. Their main goal
      will be to cover an area of the environment for later creating an ad-hoc
      communication network, that can be used to establish communications inside this
      zone. Although there are several papers on robotic deployment it is more
      difficult to find applications with UAV systems, mainly because of the existence
      of various problems that must be overcome including limitations in available
      sensory and on-board processing capabilities and low flight endurance. In
      addition, those behaviours designed for UAVs often have significant limitations
      on their ability to be used in real tasks, because they assume specific features,
      not easily applicable in a general way. Firstly, in this article the
      characteristics of the simulation environment will be presented. Secondly, a
      microscopic model for deployment and creation of ad-hoc networks, that implicitly
      includes stigmergy features, will be shown. Then, the overall swarm behaviour
      will be modeled, providing a macroscopic model of this behaviour. This model can
      accurately predict the number of agents needed to cover an area as well as the
      time required for the deployment process. An experimental analysis through
      simulation will be carried out in order to verify our models. In this analysis
      the influence of both the complexity of the environment and the stigmergy system
      will be discussed, given the data obtained in the simulation. In addition, the
      macroscopic and microscopic models will be compared verifying the number of
      predicted individuals for each state regarding the simulation.

PMID- 29370204
TI  - Correction: PARS risk charts: A 10-year study of risk assessment for
      cardiovascular diseases in Eastern Mediterranean Region.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189389.].

PMID- 29370205
TI  - Sex differences in obesity related cancer incidence in relation to type 2
      diabetes diagnosis (ZODIAC-49).
AB  - BACKGROUND: Diabetes and obesity seem to be partly overlapping risk factors for
      the development of obesity-related cancer (mainly breast, prostate and colorectal
      cancer) in patients with type 2 diabetes (T2DM). In the general population, women
      have a lower risk for obesity-related cancer compared to men. Previous studies
      involving cardiovascular disease have shown that T2DM eliminates a female
      advantage of lower CVD risk in the general population compared to men. It is
      unclear whether the same could be true for obesity-related cancer. This study
      aimed to this investigate obesity-related cancer incidence in women and men known
      with T2DM as compared to the Dutch general population. METHODS: This study
      included 69,583 patients with T2DM selected from a prospective primary care
      cohort, which was linked to the Dutch National Cancer Registry to obtain cancer
      specific data. Obesity-related cancers included liver, kidney, colorectal,
      gallbladder, pancreas, ovarian, endometrial, advanced prostate cancer, post
      menopausal breast cancer and oesophageal adenocarcinoma. Primary outcome was sex
      stratified, age and year of cancer diagnosis adjusted standardized incidence
      ratios (SIRs) for three time periods: 5 years before, the year after diagnosis
      and the next 4 years after T2DM diagnosis. The Dutch general population was used
      as reference group. RESULTS: Women with T2DM were at an increased risk for
      obesity-related cancer compared to women in the general population already 5
      years before diabetes diagnosis (SIR 1.77; 95%CI: 1.63-1.91). In both men and
      women, there was a peak in obesity-related cancer incidence following diabetes
      diagnosis (SIR: 1.38; 95%CI 1.11-1.64 and SIR: 2.21; 95%CI 1.94-2.30,
      respectively). From the second to the fifth year after diabetes diagnosis the
      obesity-related cancer incidence was higher in women compared to women in the
      general population (SIR: 2.12; 95%CI 1.94-2.30). CONCLUSIONS: Women with T2DM
      seem to have a substantially higher obesity-related cancer risk. As opposed to
      men, in women this risk was already increased years before diabetes diagnosis.
      These results could imply that a relative advantage of women in the general
      population with regard to cancer risk is lost in women with T2DM.

PMID- 29370206
TI  - Evaluating and optimizing the operation of the hydropower system in the Upper
      Yellow River: A general LINGO-based integrated framework.
AB  - The hydropower system in the Upper Yellow River (UYR), one of the largest
      hydropower bases in China, plays a vital role in the energy structure of the
      Qinghai Power Grid. Due to management difficulties, there is still considerable
      room for improvement in the joint operation of this system. This paper presents a
      general LINGO-based integrated framework to study the operation of the UYR
      hydropower system. The framework is easy to use for operators with little
      experience in mathematical modeling, takes full advantage of LINGO's capabilities
      (such as its solving capacity and multi-threading ability), and packs its three
      layers (the user layer, the coordination layer, and the base layer) together into
      an integrated solution that is robust and efficient and represents an effective
      tool for data/scenario management and analysis. The framework is general and can
      be easily transferred to other hydropower systems with minimal effort, and it can
      be extended as the base layer is enriched. The multi-objective model that
      represents the trade-off between power quantity (i.e., maximum energy production)
      and power reliability (i.e., firm output) of hydropower operation has been
      formulated. With equivalent transformations, the optimization problem can be
      solved by the nonlinear programming (NLP) solvers embedded in the LINGO software,
      such as the General Solver, the Multi-start Solver, and the Global Solver. Both
      simulation and optimization are performed to verify the model's accuracy and to
      evaluate the operation of the UYR hydropower system. A total of 13 hydropower
      plants currently in operation are involved, including two pivotal storage
      reservoirs on the Yellow River, which are the Longyangxia Reservoir and the
      Liujiaxia Reservoir. Historical hydrological data from multiple years (2000-2010)
      are provided as input to the model for analysis. The results are as follows. 1)
      Assuming that the reservoirs are all in operation (in fact, some reservoirs were
      not operational or did not collect all of the relevant data during the study
      period), the energy production is estimated as 267.7, 357.5, and 358.3*108 KWh
      for the Qinghai Power Grid during dry, normal, and wet years, respectively. 2)
      Assuming that the hydropower system is operated jointly, the firm output can
      reach 3110 MW (reliability of 100%) and 3510 MW (reliability of 90%). Moreover, a
      decrease in energy production from the Longyangxia Reservoir can bring about a
      very large increase in firm output from the hydropower system. 3) The maximum
      energy production can reach 297.7, 363.9, and 411.4*108 KWh during dry, normal,
      and wet years, respectively. The trade-off curve between maximum energy
      production and firm output is also provided for reference.

PMID- 29370208
TI  - Coronary magnetic resonance imaging after routine implantation of bioresorbable
      vascular scaffolds allows non-invasive evaluation of vascular patency.
AB  - BACKGROUND: Evaluation of recurrent angina after percutaneous coronary
      interventions is challenging. Since bioresorbable vascular scaffolds (BVS) cause
      no artefacts in magnetic resonance imaging (MRI) due to their polylactate-based
      backbone, evaluation of vascular patency by MRI might allow for non-invasive
      assessment and triage of patients with suspected BVS failure. METHODS: Patients
      with polylactate-based ABSORB-BVS in proximal coronary segments were examined
      with 3 Tesla MRI directly (baseline) and one year after implantation. For
      assessment of coronary patency, a high-resolution 3D spoiled gradient echo pulse
      sequence with fat-saturation, T2-preparation (TE: 40 ms), respiratory and end
      diastolic cardiac gating, and a spatial resolution of (1.08 mm)3 was positioned
      parallel to the course of the vessel for bright blood imaging. In addition, a 3D
      navigator-gated T2-weighted variable flip angle turbo spin echo (TSE) sequence
      with dual-inversion recovery black-blood preparation and elliptical k-space
      coverage was applied with a voxel size of (1.14 mm)3. For quantitative evaluation
      lumen diameters of the scaffolded areas were measured in reformatted bright and
      black blood MR angiography data. RESULTS: 11 patients with implantation of 16 BVS
      in the proximal coronary segments were included, of which none suffered from
      major adverse cardiac events during the one year follow up. Vascular patency in
      all segments implanted with BVS could be reliably assessed by MRI at baseline and
      after one year, whereas segments with metal stents could not be evaluated due to
      artefacts. Luminal diameter within the BVS remained constant during the one year
      period. One patient with atypical angina after BVS implantation was noninvasively
      evaluated showing a patent vessel, also confirmed by coronary angiography.
      CONCLUSIONS: Coronary MRI allows contrast-agent free and non-invasive assessment
      of vascular patency after ABSORB-BVS implantation. This approach might be
      supportive in the triage and improvement of diagnostic workflows in patients with
      postinterventional angina and scaffold implantation. TRIAL REGISTRATION: German
      Register of Clinical Studies DRKS00007456.

PMID- 29370209
TI  - Evaluation of drug mechanism and efficacy of a novel anti-angiogenic agent, TTAC
      0001, using multi-modality bioimaging in a mouse breast cancer orthotopic model.
AB  - PURPOSE: Targeting of vascular endothelial growth factor receptors (VEGFRs) has
      potential anti-angiogenic effects because VEGFR-2 is the major signaling
      regulator of VEGF/VEGFR pathways. We aimed to elucidate the drug mechanism and
      anti-tumor efficacy of TTAC-0001, a novel, fully human anti-VEGFR-2/KDR
      monoclonal antibody, in mouse orthotopic breast cancer model using multi-modal
      bioimaging. MATERIALS AND METHODS: We used orthotopic xenograft tumor model in
      which human breast cancer cells (MDA-MB-231) were injected into the right mammary
      fat pad of Balb/c nude mice. We investigated its biodistribution using serial
      fluorescence imaging after injecting fluorescent-labelled-drug and mode of action
      using Matrigel plug angiogenesis assays. The anti-tumor efficacy of drug was
      assessed using ultrasonography and bioluminescence imaging. Histopathologic
      analyses, including hematoxylin and eosin staining and immunohistochemistry with
      anti-CD31 and anti-Ki-67 antibodies, were performed. Each experiment had four
      groups: control, bevacizumab 10 mg/kg (BVZ-10 group), TTAC-0001 2 mg/kg (TTAC-2
      group), and TTAC-0001 10 mg/kg (TTAC-10 group). RESULTS: The TTAC-10 group showed
      good tumor targeting that lasted for at least 6 days and had a good anti
      angiogenic effect with decreased hemoglobin content and fewer CD31-positive cells
      in the Matrigel plug. Compared with BVZ-10 and TTAC-2 groups, the TTAC-10 group
      showed the strongest anti-tumor efficacy, inhibiting tumor growth as detected by
      ultrasonography and bioluminescence imaging. The TTAC-10 group also showed the
      lowest viable tumor and micro-vessel areas and the lowest Ki-67 index in
      histopathologic analyses. CONCLUSION: We firstly demonstrated that TTAC-0001
      effectively inhibited tumor growth and neovascularization in mouse orthotopic
      breast cancer model. It may provide a future treatment option for breast cancer.

PMID- 29370207
TI  - APOEepsilon4 and slow wave sleep in older adults.
AB  - Slow wave (or stage N3) sleep has been linked to a variety of cognitive
      processes. However, the role of stage N3 in the elderly is debated. The link
      between stage N3 and episodic memory may be weakened or changed in the older
      adult population, possibly due to several altered mechanisms impacting the
      cellular structure of the brain. The bases for the age-related dissociation
      between stage N3 and cognition are not understood. Since APOEepsilon4 status is
      the strongest genetic risk factor for cognitive decline, we assessed whether the
      epsilon4 allele is associated with stage N3 sleep. Participants were from the
      population-based Osteoporotic Fractures in Men (MrOS) cohort with polysomnography
      and APOEepsilon4 genotype data (n = 2,302, 100% male, mean age 76.6 years). Sleep
      stages were objectively measured using overnight in-home polysomnography and
      central electroencephalogram data were used to score stage N3 sleep. Cognitive
      function was assessed using the Modified Mini Mental State Exam (3MS). The APOE
      rs429358 single nucleotide polymorphism, which defines the APOEepsilon4 allele,
      was genotyped using a custom genotyping array. Total time in stage N3 sleep was
      significantly higher (p<0.0001) among the 40 MrOS participants carrying two
      copies of the epsilon4 allele (62+/-5.2 minutes) compared with 43+/-1.5 minutes
      for carriers of one epsilon4 allele (n = 515) and 40+/-0.8 minutes for epsilon4
      non-carriers (n = 1747). All results were independent of sleep efficiency, number
      of sleep cycles, and apnea hypopnea index. These findings support an association
      between APOEepsilon4 genotype and sleep stage N3 in the elderly. Increased total
      stage N3 duration among epsilon4/epsilon4 carriers does not appear to reflect
      compensation for prior cognitive decline and may reflect overactive downscaling
      of synapses during sleep. If confirmed, these results might in part explain the
      high risk of age-related cognitive decline and AD among APOE epsilon4/epsilon4
      carriers.

PMID- 29370210
TI  - Integrated phenotypic-genotypic approach to understand the influence of
      ultrasound on metabolic response of Lactobacillus sakei.
AB  - The lethal effects of soundwaves on a range of microorganisms have been known for
      almost a century whereas, the use of ultrasound to promote or control their
      activity is much more recent. Moreover, the fundamental molecular mechanism
      influencing the behaviour of microorganisms subjected to ultrasonic waves is not
      well established. In this study, we investigated the influence of ultrasonic
      frequencies of 20, 45, 130 and 950 kHz on growth kinetics of Lactobacillus sakei.
      A significant increase in the growth rate of L. sakei was observed following
      ultrasound treatment at 20 kHz despite the treatment yielding a significant
      reduction of ca. 3 log cfu/mL in cells count. Scanning electron microscopy showed
      that ultrasound caused significant changes on the cell surface of L. sakei
      culture with the formation of pores "sonoporation". Phenotypic microarrays showed
      that all ultrasound treated L. sakei after exposure to various carbon, nitrogen,
      phosphorus and sulphur sources had significant variations in nutrient
      utilisation. Integration of this phenotypic data with the genome of L. sakei
      revealed that various metabolic pathways were being influenced by the ultrasound
      treatments. Results presented in this study showed that the physiological
      response of L. sakei in response to US is frequency dependent and that it can
      influence metabolic pathways. Hence, ultrasound treatments can be employed to
      modulate microbial activity for specialised applications.

PMID- 29370211
TI  - Osteoclast inhibitors to prevent bone metastases in men with high-risk, non
      metastatic prostate cancer: A systematic review and meta-analysis.
AB  - BACKGROUND: In advanced prostate cancer, osteoclast inhibitors prevent and
      palliate skeletal related events associated with bone metastases. However, it is
      uncertain whether they play a disease-modifying role earlier in the course of the
      disease. METHODS: Medline, EMBASE, Cochrane Central Register of Controlled Trials
      and Cochrane Database of Systematic Reviews and ASCO conference proceedings were
      searched for randomized controlled trials that compared osteoclast inhibitors
      with placebo and/or standard of care (SOC) in patients with high-risk, non
      metastatic prostate cancer. The primary outcome measure was incidence of new bone
      metastases; secondary outcomes included overall survival (OS), prostate cancer
      specific survival, mortality unrelated to prostate cancer, toxicity and health
      related quality of life outcomes. Results are presented as relative risk (RR)
      with 95% confidence intervals (CI). RESULTS: Six randomized controlled trials
      (5947 participants) were included, five evaluating bisphosphonates and one
      denosumab. Overall, there was no difference in incidence of bone metastases
      between participants treated with osteoclast inhibitors versus placebo/SOC (RR
      1.09, 95%CI 0.84-1.41, p = 0.51) however significant heterogeneity was observed
      between studies. The denosumab trial was the largest and only positive trial
      amongst the included studies (RR 0.83, 95%CI 0.73-0.95, p = 0.007). No
      significant difference was observed in OS (RR 0.99 95% CI 0.89-1.10, p = 0.84)
      nor prostate cancer specific survival (RR 1.12 95%CI 0.93-1.36, p = 0.24). Most
      studies reported increased rates of osteonecrosis of the jaw (5% or less) and
      hypocalcemia (2% or less) with osteoclast inhibitors. CONCLUSIONS: While there is
      limited evidence that bisphosphonates alter the natural history of high-risk, non
      metastatic prostate cancer, denosumab delays onset of bone metastases in this
      patient population. Neither class of osteoclast inhibitor demonstrated an impact
      on survival outcomes. Future trials with better defined patient selection and a
      robust definition for high risk disease is critical.

PMID- 29370212
TI  - Not explicit but implicit memory is influenced by individual perception style.
AB  - Not only explicit but also implicit memory has considerable influence on our
      daily life. However, it is still unclear whether explicit and implicit memories
      are sensitive to individual differences. Here, we investigated how individual
      perception style (global or local) correlates with implicit and explicit memory.
      As a result, we found that not explicit but implicit memory was affected by the
      perception style: local perception style people more greatly used implicit memory
      than global perception style people. These results help us to make the new
      effective application adapting to individual perception style and understand some
      clinical symptoms such as autistic spectrum disorder. Furthermore, this finding
      might give us new insight of memory involving consciousness and unconsciousness
      as well as relationship between implicit/explicit memory and individual
      perception style.

PMID- 29370213
TI  - Early life vitamin D depletion alters the postnatal response to skeletal loading
      in growing and mature bone.
AB  - There is increasing evidence of persistent effects of early life vitamin D
      exposure on later skeletal health; linking low levels in early life to smaller
      bone size in childhood as well as increased fracture risk later in adulthood,
      independently of later vitamin D status. A major determinant of bone mass
      acquisition across all ages is mechanical loading. We tested the hypothesis in an
      animal model system that early life vitamin D depletion results in abrogation of
      the response to mechanical loading, with consequent reduction in bone size, mass
      and strength during both childhood and adulthood. A murine model was created in
      which pregnant dams were either vitamin D deficient or replete, and their
      offspring moved to a vitamin D replete diet at weaning. Tibias of the offspring
      were mechanically loaded and bone structure, extrinsic strength and growth
      measured both during growth and after skeletal maturity. Offspring of vitamin D
      deplete mice demonstrated lower bone mass in the non loaded limb and reduced bone
      mass accrual in response to loading in both the growing skeleton and after
      skeletal maturity. Early life vitamin D depletion led to reduced bone strength
      and altered bone biomechanical properties. These findings suggest early life
      vitamin D status may, in part, determine the propensity to osteoporosis and
      fracture that blights later life in many individuals.

PMID- 29370214
TI  - Alcohol and older people: A systematic review of barriers, facilitators and
      context of drinking in older people and implications for intervention design.
AB  - BACKGROUND: Harmful alcohol consumption in older people has increased and
      effective approaches to understanding and addressing this societal concern are
      needed. METHODS: Systematic review of qualitative studies in older populations
      (55+ years) to identify barriers, facilitators or context of drinking in older
      people. Multiple databases (MEDLINE, EMBASE, PsycINFO, CINAHL, CENTRAL, Social
      Sciences Citation Index, York Centre for Reviews and Dissemination, Cochrane
      database and grey literature) were searched from 2000 to February 2017 for
      studies in English, from OECD countries using MeSH terms and text words relating
      to alcohol combined with older age terms. Study quality was assessed using NICE
      methodology. The review is reported according to PRISMA. RESULTS: Drinking in
      older people is strongly linked to social engagement and there is scepticism
      about the health risks of alcohol. Drinking was also linked to difficulties such
      as social isolation, illness or bereavement. Alcohol can be related to routines
      and identity. However, older people often regulate their own drinking and
      strategies that emphasise the life experience of older people to drink wisely
      could be helpful. CONCLUSIONS: To be effective societal approaches need to take
      into account contexts of risks for harmful drinking. The evidence supports a
      strong social role for drinking alcohol which should be taken into account in any
      policy development with the potential benefits of social participation for
      cognitive health. Approaches to reducing alcohol use in older people need to
      avoid paradoxical harm, with a need for approaches that reduce harm from drinking
      alcohol but retain the benefit of socialising.

PMID- 29370215
TI  - High levels of incidental physical activity are positively associated with
      cognition and EEG activity in aging.
AB  - High levels of physical activity seem to positively influence health and
      cognition across the lifespan. Several studies have found that aerobic exercise
      enhances cognition and likely prevents cognitive decline in the elderly.
      Nevertheless, the association of incidental physical activity (IPA) with health
      and cognition during aging has not been studied. Thus, the aim of this study was
      to evaluate the association of IPA level with cognitive functions and resting
      electroencephalogram (EEG) in healthy old participants. Participants (n = 97)
      with normal scores on psychometric and neuropsychological tests and normal values
      in blood analyses were included. A cluster analysis based on the scores of the
      Yale Physical Activity Scale (YPAS) allowed the formation of two groups: active,
      with high levels of IPA, and passive, with low levels of IPA. Eyes-closed resting
      EEG was recorded from the participants; the fast Fourier transform was used
      offline to calculate absolute power (AP), relative power (RP), and mean frequency
      (MF) measures. There were no differences in socioeconomic status, cognitive
      reserve, general cognitive status, or lipid and TSH profiles between the groups.
      The results of cognitive tests revealed significant differences in the
      performance variables of the WAIS scores (p = .015), with advantages for the
      active group. The resting EEG exhibited significantly slower activity involving
      the frontal, central, and temporal regions in the passive group (p < .05).
      Specifically, higher delta RP (F7, T3), lower delta MF (F4, C4, T4, T6, Fz, Cz),
      higher theta AP (C4), higher theta RP (F4, C4, T3, Fz), lower alpha AP (F3, F7,
      T3), lower alpha RP (F7), and lower total MF (F3, F7, T3, T5, Fz) were found.
      Altogether, these results suggest that IPA induces a neuroprotective effect,
      which is reflected both in behavioral and electrophysiological variables during
      aging.

PMID- 29370216
TI  - Compensating for geographic variation in detection probability with water depth
      improves abundance estimates of coastal marine megafauna.
AB  - The probability of an aquatic animal being available for detection is typically
      <1. Accounting for covariates that reduce the probability of detection is
      important for obtaining robust estimates of the population abundance and
      determining its status and trends. The dugong (Dugong dugon) is a bottom-feeding
      marine mammal and a seagrass community specialist. We hypothesized that the
      probability of a dugong being available for detection is dependent on water depth
      and that dugongs spend more time underwater in deep-water seagrass habitats than
      in shallow-water seagrass habitats. We tested this hypothesis by quantifying the
      depth use of 28 wild dugongs fitted with GPS satellite transmitters and time
      depth recorders (TDRs) at three sites with distinct seagrass depth distributions:
      1) open waters supporting extensive seagrass meadows to 40 m deep (Torres Strait,
      6 dugongs, 2015); 2) a protected bay (average water depth 6.8 m) with extensive
      shallow seagrass beds (Moreton Bay, 13 dugongs, 2011 and 2012); and 3) a mixture
      of lagoon, coral and seagrass habitats to 60 m deep (New Caledonia, 9 dugongs,
      2013). The fitted instruments were used to measure the times the dugongs spent in
      the experimentally determined detection zones under various environmental
      conditions. The estimated probability of detection was applied to aerial survey
      data previously collected at each location. In general, dugongs were least
      available for detection in Torres Strait, and the population estimates increased
      6-7 fold using depth-specific availability correction factors compared with
      earlier estimates that assumed homogeneous detection probability across water
      depth and location. Detection probabilities were higher in Moreton Bay and New
      Caledonia than Torres Strait because the water transparency in these two
      locations was much greater than in Torres Strait and the effect of correcting for
      depth-specific detection probability much less. The methodology has application
      to visual survey of coastal megafauna including surveys using Unmanned Aerial
      Vehicles.

PMID- 29370217
TI  - Does ambient noise or hypobaric atmosphere influence olfactory and gustatory
      function?
AB  - Multidimensional food perception is based mainly on gustatory and olfactory
      function. Recent research has demonstrated that hypobaric pressure impairs
      gustatory function and that background noise or distracting auditory stimulation
      impairs olfactory function. Using a hypobaric chamber, the odor identification,
      discrimination, and thresholds as well as taste identification and threshold
      scores were measured in 16 healthy male volunteers under normal and hypobaric
      (6380 ft) conditions using clinically validated tests. In both conditions,
      background noise was either canceled out or replaced by white noise presentation
      (70 dB sound pressure level). Olfactory sensitivity for n-butanol and gustatory
      sensitivity were impaired in a hypobaric atmosphere. White noise did not
      influence the odor test results. White noise stimulation impaired sensitivity for
      sour and sweet but not for bitter or salty tastants. We conclude that hypobaric
      or noisy environments could impair gustatory and olfactory sensitivity
      selectively for particular tastants and odorants.

PMID- 29370218
TI  - The effect of concomitant DPPIVi use on glycaemic control and hypoglycaemia with
      insulin glargine 300 U/mL (Gla-300) versus insulin glargine 100 U/mL (Gla-100) in
      people with type 2 diabetes: A patient-level meta-analysis of EDITION 2 and 3.
AB  - AIMS: To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor
      (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus
      glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral
      antihyperglycaemic drugs. METHODS: A post hoc patient-level meta-analysis was
      performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3
      (insulin-naive [N = 878]), multicentre, randomised, open-label, parallel-group,
      phase 3a trials of similar design. Endpoints analysed included HbA1c,
      hypoglycaemia and adverse events, investigated in subgroups of participants with
      and without concomitant DPPIVi use. RESULTS: Of 1689 participants randomised, 107
      (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares
      mean change in HbA1c (baseline to month 6) was comparable between treatment
      groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment
      effect across subgroups, p = 0.753), although group sizes were unbalanced. The
      cumulative mean number of confirmed (<=3.9 mmol/L [<=70 mg/dL]) or severe
      hypoglycaemic events, and the risk and annualised rate of such events, were
      consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and
      05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe
      hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla
      100 groups, respectively, and was not affected by DPPIVi use. The adverse event
      profile was similar between treatment groups and DPPIVi subgroups. CONCLUSIONS:
      Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia
      during the night and at any time of day (24 h), irrespective of concomitant
      DPPIVi use. TRIAL REGISTRATION: ClinicalTrials.gov NCT01499095; NCT01676220.

PMID- 29370219
TI  - ARMC5 mutations in familial and sporadic primary bilateral macronodular adrenal
      hyperplasia.
AB  - To investigate Armadillo repeat-containing 5 (ARMC5) mutations in Chinese
      patients with familial and sporadic primary bilateral macronodular adrenal
      hyperplasia (PBMAH), we performed clinical data collection and ARMC5 sequencing
      for three PBMAH families and 23 sporadic PBMAH patients. ARMC5 pathogenic
      germline mutations were identified in all 3 PBMAH families. Secondary ARMC5
      somatic mutations were found in two adrenal nodules from two PBMAH family members
      with ARMC5 germline mutations. PBMAH family members with ARMC5 pathogenic
      germline mutations displayed various clinical manifestations. ARMC5 pathogenic
      germline mutations were identified in 5 sporadic PBMAH patients among whom one
      patient displayed both hypercortisolism and primary aldosteronism. We detected a
      total of 10 ARMC5 pathogenic mutations, of which 8 had not been previously
      reported. Our results suggest that ARMC5 pathogenic germline mutations are common
      in familial and sporadic Chinese PBMAH patients, and demonstrate the importance
      of ARMC5 screening in PBMAH family members to detect patients with insidious
      PBMAH.

PMID- 29370220
TI  - Women's experiences with unplanned pregnancy and abortion in Kenya: A qualitative
      study.
AB  - BACKGROUND: Safe and legal abortions are rarely practiced in the public health
      sector in Kenya, and rates of maternal mortality and morbidity from unsafe
      abortion is high. Little is known about women's experiences seeking and accessing
      abortion in informal settlements in Nairobi, Kenya. METHODS: Seven focus group
      discussions were conducted with a total of 71 women and girls recruited from an
      informal settlement in Nairobi. The interview guide explored participants'
      perceptions of unplanned pregnancy, abortion, and access to sexual and
      reproductive health information in their community. Thematic analysis of the
      focus group transcripts was conducted using MAX QDA Release 12. RESULTS:
      Participants described a variety of factors that influence women's experiences
      with abortion in their communities. According to participants, limited knowledge
      of sexual and reproductive health information and lack of access to contraception
      led to unplanned pregnancy among women in their community. Participants cited
      stigma and loss of opportunities that women with unplanned pregnancies face as
      the primary reasons why women seek abortions. Participants articulated stigma as
      the predominant barrier women in their communities face to safe abortion. Other
      barriers, which were often interrelated to stigma, included lack of education
      about safe methods of abortion, perceived illegality of abortion, as well as
      limited access to services, fear of mistreatment, and mistrust of health
      providers and facilities. CONCLUSIONS: Women in informal settlements in Nairobi,
      Kenya face substantial barriers to regulating their fertility and lack access to
      safe abortion. Policy makers and reproductive health advocates should support
      programs that employ harm reduction strategies and increase women's knowledge of
      and access to medication abortion outside the formal healthcare system.

PMID- 29370221
TI  - Surface display of OmpC of Salmonella serovar Pullorum on Bacillus subtilis
      spores.
AB  - Salmonellosis is a major public health problem throughout the world. Thus, there
      is a huge need for diversified control strategies for Salmonella infections. In
      this work, we have assessed the potential use of Bacillus subtilis (B. subtilis)
      spores for the expression of a major protective antigen of Salmonella serovar
      Pullorum, OmpC. The expression of OmpC on the surface of spores was determined by
      immunofluorescence microscopy. Mice immunized with recombinant spores expressing
      the OmpC antigen presented significant levels of OmpC-specific serum IgG and
      mucosal SIgA antibodies than in mice immunized with non-recombinant spores
      (p<0.01). In addition, oral immunization with recombinant spores was able to
      induce a significant level of protection in mice against lethal challenge with
      Salmonella serovar Typhimurium. These results suggest that B. subtilis spores
      have promising potential in the development of mucosal vaccines against
      Salmonella infections.

PMID- 29370222
TI  - A tradeoff between the losses caused by computer viruses and the risk of the
      manpower shortage.
AB  - This article addresses the tradeoff between the losses caused by a new virus and
      the size of the team for developing an antivirus against the virus. First, an
      individual-level virus spreading model is proposed to capture the spreading
      process of the virus before the appearance of its natural enemy. On this basis,
      the tradeoff problem is modeled as a discrete optimization problem. Next, the
      influences of different factors, including the infection force, the infection
      function, the available manpower, the alarm threshold, the antivirus development
      effort and the network topology, on the optimal team size are examined through
      computer simulations. This work takes the first step toward the tradeoff problem,
      and the findings are instructive to the decision makers of network security
      companies.

PMID- 29370223
TI  - Breeding sex ratio and population size of loggerhead turtles from Southwestern
      Florida.
AB  - Species that display temperature-dependent sex determination are at risk as a
      result of increasing global temperatures. For marine turtles, high incubation
      temperatures can skew sex ratios towards females. There are concerns that
      temperature increases may result in highly female-biased offspring sex ratios,
      which would drive a future sex ratio skew. Studying the sex ratios of adults in
      the ocean is logistically very difficult because individuals are widely
      distributed and males are inaccessible because they remain in the ocean. Breeding
      sex ratios (BSR) are sought as a functional alternative to study adult sex
      ratios. One way to examine BSR is to determine the number of males that
      contribute to nests. Our goal was to evaluate the BSR for loggerhead turtles
      (Caretta caretta) nesting along the eastern Gulf of Mexico in Florida, from 2013
      2015, encompassing three nesting seasons. We genotyped 64 nesting females
      (approximately 28% of all turtles nesting at that time) and up to 20 hatchlings
      from their nests (n = 989) using 7 polymorphic microsatellite markers. We
      identified multiple paternal contributions in 70% of the nests analyzed and 126
      individual males. The breeding sex ratio was approximately 1 female for every 2.5
      males. We did not find repeat males in any of our nests. The sex ratio and lack
      of repeating males was surprising because of female-biased primary sex ratios. We
      hypothesize that females mate offshore of their nesting beaches as well as en
      route. We recommend further comparisons of subsequent nesting events and of other
      beaches as it is imperative to establish baseline breeding sex ratios to
      understand how growing populations behave before extreme environmental effects
      are evident.

PMID- 29370224
TI  - Linking deep convection and phytoplankton blooms in the northern Labrador Sea in
      a changing climate.
AB  - Wintertime convective mixing plays a pivotal role in the sub-polar North Atlantic
      spring phytoplankton blooms by favoring phytoplankton survival in the competition
      between light-dependent production and losses due to grazing and gravitational
      settling. We use satellite and ocean reanalyses to show that the area-averaged
      maximum winter mixed layer depth is positively correlated with April chlorophyll
      concentration in the northern Labrador Sea. A simple theoretical framework is
      developed to understand the relative roles of winter/spring convection and
      gravitational sedimentation in spring blooms in this region. Combining climate
      model simulations that project a weakening of wintertime Labrador Sea convection
      from Arctic sea ice melt with our framework suggests a potentially significant
      reduction in the initial fall phytoplankton population that survive the winter to
      seed the region's spring bloom by the end of the 21st century.

PMID- 29370226
TI  - A critical comparison of topology-based pathway analysis methods.
AB  - One of the aims of high-throughput gene/protein profiling experiments is the
      identification of biological processes altered between two or more conditions.
      Pathway analysis is an umbrella term for a multitude of computational approaches
      used for this purpose. While in the beginning pathway analysis relied on
      enrichment-based approaches, a newer generation of methods is now available,
      exploiting pathway topologies in addition to gene/protein expression levels.
      However, little effort has been invested in their critical assessment with
      respect to their performance in different experimental setups. Here, we assessed
      the performance of seven representative methods identifying differentially
      expressed pathways between two groups of interest based on gene expression data
      with prior knowledge of pathway topologies: SPIA, PRS, CePa, TAPPA, TopologyGSA,
      Clipper and DEGraph. We performed a number of controlled experiments that
      investigated their sensitivity to sample and pathway size, threshold-based
      filtering of differentially expressed genes, ability to detect target pathways,
      ability to exploit the topological information and the sensitivity to different
      pre-processing strategies. We also verified type I error rates and described the
      influence of overexpression of single genes, gene sets and topological motifs of
      various sizes on the detection of a pathway as differentially expressed. The
      results of our experiments demonstrate a wide variability of the tested methods.
      We provide a set of recommendations for an informed selection of the proper
      method for a given data analysis task.

PMID- 29370225
TI  - Examining the role of common and rare mitochondrial variants in schizophrenia.
AB  - Oxidative phosphorylation within mitochondria is the main source of aerobic
      energy for neuronal functioning, and the key genes are located in mitochondrial
      DNA. Deficits in oxidative phosphorylation functioning have been reported for
      schizophrenia, but efforts in the identification of genetic markers within the
      mitochondrial DNA that predispose to schizophrenia have been limited. We
      genotyped a set of mitochondrial SNPs using Illumina HumanExome arrays and tested
      for association in the Swedish schizophrenia sample (N> 10,000). We developed a
      novel approach for mitochondrial DNA imputation in order to increase the number
      of common SNPs available for association analysis. The most significant findings
      were for the mitochondrial SNPs C15452A (GRCh38.p10; rs527236209; p = 0.007; gene
      MT-CYB; defining haplogroup JT); A11251G (rs869096886; p = 0.007; gene MT-ND4;
      defining haplogroup JT), and T4216C (rs1599988; p = 0.008, gene MT-ND1, defining
      haplogroup R2'JT). We also conducted rare variant burden analyses and obtained a
      p-value of 0.007. For multimarker haplotypes analysis, the most significant
      finding was for the J group (OR: 0.86, p = 0.02). We conducted the largest
      association study of mitochondrial DNA variants and schizophrenia but did not
      find an association that survived multiple testing correction. Analysis of a
      larger sample is required and will allow a better understanding of the role of
      mitochondria in schizophrenia.

PMID- 29370227
TI  - Associations between malaria-related ideational factors and care-seeking behavior
      for fever among children under five in Mali, Nigeria, and Madagascar.
AB  - Malaria remains one of the leading causes of morbidity and mortality among
      children under five years old in many low- and middle-income countries. In this
      study, we examined how malaria-related ideational factors may influence care
      seeking behavior among female caregivers of children under five with fever. Data
      came from population-based surveys conducted in 2014-2015 by U.S. Agency for
      International Development-funded surveys in Madagascar, Mali, and Nigeria. The
      outcome of interest was whether a child under five with fever within two weeks
      prior to the survey was brought to a formal health facility for care. Results
      show a wide variation in care-seeking practices for children under five with
      fever across countries. Seeking care for febrile children under five in the
      formal health sector is far from a norm in the study countries. Important
      ideational factors associated with care-seeking behavior included caregivers'
      perceived social norms regarding treatment of fever among children under five in
      Nigeria and Madagascar, and caregiver's knowledge of the cause of malaria in
      Mali. Findings indicate that messages aimed to increase malaria-related knowledge
      should be tailored to the specific country, and that interventions designed to
      influence social norms about care-seeking are likely to result in increased care
      seeking behavior for fever in children under five.

PMID- 29370228
TI  - Regional differences in antihyperglycemic medication are not explained by
      individual socioeconomic status, regional deprivation, and regional health care
      services. Observational results from the German DIAB-CORE consortium.
AB  - AIMS: This population-based study sought to extend knowledge on factors
      explaining regional differences in type 2 diabetes mellitus medication patterns
      in Germany. METHODS: Individual baseline and follow-up data from four regional
      population-based German cohort studies (SHIP [northeast], CARLA [east], HNR
      [west], KORA [south]) conducted between 1997 and 2010 were pooled and merged with
      both data on regional deprivation and regional health care services. To analyze
      regional differences in any or newer anti-hyperglycemic medication, medication
      prevalence ratios (PRs) were estimated using multivariable Poisson regression
      models with a robust error variance adjusted gradually for individual and
      regional variables. RESULTS: The study population consisted of 1,437 people aged
      45 to 74 years at baseline, (corresponding to 49 to 83 years at follow-up) with
      self-reported type 2 diabetes. The prevalence of receiving any anti-hyperglycemic
      medication was 16% higher in KORA (PR 1.16 [1.08-1.25]), 10% higher in CARLA
      (1.10 [1.01-1.18]), and 7% higher in SHIP (PR 1.07 [1.00-1.15]) than in HNR. The
      prevalence of receiving newer anti-hyperglycemic medication was 49% higher in
      KORA (1.49 [1.09-2.05]), 41% higher in CARLA (1.41 [1.02-1.96]) and 1% higher in
      SHIP (1.01 [0.72-1.41]) than in HNR, respectively. After gradual adjustment for
      individual variables, regional deprivation and health care services, the effects
      only changed slightly. CONCLUSIONS: Neither comprehensive individual factors
      including socioeconomic status nor regional deprivation or indicators of regional
      health care services were able to sufficiently explain regional differences in
      anti-hyperglycemic treatment in Germany. To understand the underlying causes,
      further research is needed.

PMID- 29370230
TI  - Identification of transformer fault based on dissolved gas analysis using hybrid
      support vector machine-modified evolutionary particle swarm optimisation.
AB  - Early detection of power transformer fault is important because it can reduce the
      maintenance cost of the transformer and it can ensure continuous electricity
      supply in power systems. Dissolved Gas Analysis (DGA) technique is commonly used
      to identify oil-filled power transformer fault type but utilisation of artificial
      intelligence method with optimisation methods has shown convincing results. In
      this work, a hybrid support vector machine (SVM) with modified evolutionary
      particle swarm optimisation (EPSO) algorithm was proposed to determine the
      transformer fault type. The superiority of the modified PSO technique with SVM
      was evaluated by comparing the results with the actual fault diagnosis,
      unoptimised SVM and previous reported works. Data reduction was also applied
      using stepwise regression prior to the training process of SVM to reduce the
      training time. It was found that the proposed hybrid SVM-Modified EPSO (MEPSO)
      Time Varying Acceleration Coefficient (TVAC) technique results in the highest
      correct identification percentage of faults in a power transformer compared to
      other PSO algorithms. Thus, the proposed technique can be one of the potential
      solutions to identify the transformer fault type based on DGA data on site.

PMID- 29370231
TI  - Behavioural responses of krill and cod to artificial light in laboratory
      experiments.
AB  - Most fishes and crustaceans respond to light, and artificial light sources may
      therefore be an efficient stimulus to manipulate behaviours in aquatic animals.
      It has been hypothesised that the catch efficiency of pots could be increased if
      prey, for example krill, can be attracted into the pots providing a visual
      stimulus and a source of live bait. To find which light characteristics are most
      attractive to krill, we tested the effects of light intensity and wavelength
      composition on Northern krill's (Meganyctiphanes norvegica) behavioural response
      to an artificial light source. The most attractive individual wavelength was 530
      nm (green light), while broadband (425-750 nm) white light was an equally
      attractive light source. The intensity of the emitted light did not appear to
      have a direct effect on attraction to the light source, however it did
      significantly increase swimming activity among the observed krill. The most
      promising light stimuli for krill were tested to determine whether they would
      have a repulsive or attractive effect on cod (Gadus morhua); These light stimuli
      appeared to have a slightly repulsive, but non-significant, effect on cod.
      However, we suggest that a swarm of krill attracted to an artificial light source
      may produce a more effective visual stimulus to foraging cod.

PMID- 29370229
TI  - Risk factors for death, stroke, and bleeding in 28,628 patients from the GARFIELD
      AF registry: Rationale for comprehensive management of atrial fibrillation.
AB  - BACKGROUND: The factors influencing three major outcomes-death, stroke/systemic
      embolism (SE), and major bleeding-have not been investigated in a large
      international cohort of unselected patients with newly diagnosed atrial
      fibrillation (AF). METHODS AND RESULTS: In 28,628 patients prospectively enrolled
      in the GARFIELD-AF registry with 2-year follow-up, we aimed at analysing: (1) the
      variables influencing outcomes; (2) the extent of implementation of guideline
      recommended therapies in comorbidities that strongly affect outcomes. Median
      (IQR) age was 71.0 (63.0 to 78.0) years, 44.4% of patients were female, median
      (IQR) CHA2DS2-VASc score was 3.0 (2.0 to 4.0); 63.3% of patients were on
      anticoagulants (ACs) with or without antiplatelet (AP) therapy, 24.5% AP
      monotherapy, and 12.2% no antithrombotic therapy. At 2 years, rates (95% CI) of
      death, stroke/SE, and major bleeding were 3.84 (3.68; 4.02), 1.27 (1.18; 1.38),
      and 0.71 (0.64; 0.79) per 100 person-years. Age, history of stroke/SE, vascular
      disease (VascD), and chronic kidney disease (CKD) were associated with the risks
      of all three outcomes. Congestive heart failure (CHF) was associated with the
      risks of death and stroke/SE. Smoking, non-paroxysmal forms of AF, and history of
      bleeding were associated with the risk of death, female sex and heavy drinking
      with the risk of stroke/SE. Asian race was associated with lower risks of death
      and major bleeding versus other races. AC treatment was associated with 30% and
      28% lower risks of death and stroke/SE, respectively, compared with no AC
      treatment. Rates of prescription of guideline-recommended drugs were suboptimal
      in patients with CHF, VascD, or CKD. CONCLUSIONS: Our data show that several
      variables are associated with the risk of one or more outcomes, in terms of
      death, stroke/SE, and major bleeding. Comprehensive management of AF should
      encompass, besides anticoagulation, improved implementation of guideline
      recommended therapies for comorbidities strongly associated with outcomes, namely
      CHF, VascD, and CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01090362.

PMID- 29370232
TI  - Identification of QTL conferring resistance to stripe rust (Puccinia striiformis
      f. sp. hordei) and leaf rust (Puccinia hordei) in barley using nested association
      mapping (NAM).
AB  - The biotrophic rust fungi Puccinia hordei and Puccinia striiformis are important
      barley pathogens with the potential to cause high yield losses through an
      epidemic spread. The identification of QTL conferring resistance to these
      pathogens is the basis for targeted breeding approaches aiming to improve stripe
      rust and leaf rust resistance of modern cultivars. Exploiting the allelic
      richness of wild barley accessions proved to be a valuable tool to broaden the
      genetic base of resistance of barley cultivars. In this study, SNP-based nested
      association mapping (NAM) was performed to map stripe rust and leaf rust
      resistance QTL in the barley NAM population HEB-25, comprising 1,420 lines
      derived from BC1S3 generation. By scoring the percentage of infected leaf area,
      followed by calculation of the area under the disease progress curve and the
      average ordinate during a two-year field trial, a large variability of resistance
      across and within HEB-25 families was observed. NAM based on 5,715 informative
      SNPs resulted in the identification of twelve and eleven robust QTL for
      resistance against stripe rust and leaf rust, respectively. Out of these, eight
      QTL for stripe rust and two QTL for leaf rust are considered novel showing no
      overlap with previously reported resistance QTL. Overall, resistance to both
      pathogens in HEB-25 is most likely due to the accumulation of numerous small
      effect loci. In addition, the NAM results indicate that the 25 wild donor QTL
      alleles present in HEB-25 strongly differ in regard to their individual effect on
      rust resistance. In future, the NAM concept will allow to select and combine
      individual wild barley alleles from different HEB parents to increase rust
      resistance in barley. The HEB-25 results will support to unravel the genetic
      basis of rust resistance in barley, and to improve resistance against stripe rust
      and leaf rust of modern barley cultivars.

PMID- 29370233
TI  - Rapid analysis method for the determination of 14C specific activity in
      irradiated graphite.
AB  - 14C is one of the limiting radionuclides used in the categorization of
      radioactive graphite waste; this categorization is crucial in selecting the
      appropriate graphite treatment/disposal method. We propose a rapid analysis
      method for 14C specific activity determination in small graphite samples in the 1
      100 MUg range. The method applies an oxidation procedure to the sample, which
      extracts 14C from the different carbonaceous matrices in a controlled manner.
      Because this method enables fast online measurement and 14C specific activity
      evaluation, it can be especially useful for characterizing 14C in irradiated
      graphite when dismantling graphite moderator and reflector parts, or when sorting
      radioactive graphite waste from decommissioned nuclear power plants. The proposed
      rapid method is based on graphite combustion and the subsequent measurement of
      both CO2 and 14C, using a commercial elemental analyser and the semiconductor
      detector, respectively. The method was verified using the liquid scintillation
      counting (LSC) technique. The uncertainty of this rapid method is within the
      acceptable range for radioactive waste characterization purposes. The 14C
      specific activity determination procedure proposed in this study takes
      approximately ten minutes, comparing favorably to the more complicated and time
      consuming LSC method. This method can be potentially used to radiologically
      characterize radioactive waste or used in biomedical applications when dealing
      with the specific activity determination of 14C in the sample.

PMID- 29370234
TI  - Febrile urinary-tract infection due to extended-spectrum beta-lactamase-producing
      Enterobacteriaceae in children: A French prospective multicenter study.
AB  - OBJECTIVES: To assess the management of febrile urinary-tract infection (FUTIs)
      due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in
      children, the Pediatric Infectious Diseases Group of the French Pediatric Society
      set up an active surveillance network in pediatric centers across France in 2014.
      MATERIALS AND METHODS: We prospectively analysed data from 2014 to 2016 for all
      children < 18 years old who received antibiotic treatment for FUTI due to ESBL-E
      in 24 pediatric centers. Baseline demographic, clinical features, microbiological
      data and antimicrobials prescribed were collected. RESULTS: 301 children were
      enrolled in this study. The median age was 1 year (IQR 0.02-17.9) and 44.5% were
      male. These infections occurred in children with history of UTIs (27.3%) and
      urinary malformations (32.6%). Recent antibiotic use was the main associated
      factor for FUTIs due to ESBL-E, followed by a previous hospitalization and travel
      history. Before drug susceptibility testing (DST), third-generation
      cephalosporins (3GC) PO/IV were the most-prescribed antibiotics (75.5%). Only 13%
      and 24% of children received amikacine alone for empirical or definitive therapy,
      respectively, whereas 88.7% of children had isolates susceptible to amikacin. In
      all, 23.2% of children received carbapenems in empirical and/or definitive
      therapy. Cotrimoxazole (24.5%), ciprofloxacin (15.6%) and non-orthodox
      clavulanate-cefixime combination (31.3%) were the most frequently prescribed oral
      options after obtaining the DST. The time to apyrexia and length of hospital stay
      did not differ with or without effective empirical therapy. CONCLUSIONS: We
      believe that amikacin should increasingly take on a key role in the choice of
      definitive therapy of FUTI due to ESBL-E in children by avoiding the use of
      carbapenems.

PMID- 29370235
TI  - Time-limited involvement of caudal anterior cingulate cortex in trace eyeblink
      conditioning retrieval is dependent on conditioned stimulus intensity.
AB  - The medial prefrontal cortex (mPFC) has been widely investigated for its roles in
      learning and memory. The present study investigated the time-limited involvement
      of the caudal anterior cingulate cortex (cACC) of the mPFC in the retrieval
      process for a simple associative motor learning, trace eyeblink conditioning
      (tEBC), using a 75 dB or 100 dB tone as the conditioned stimulus (CS). The GABAA
      receptor agonist muscimol was injected into the cACC of guinea pigs at 1 day or 4
      weeks after tEBC acquisition. When muscimol was administered 1 day after tEBC
      acquisition, the conditioned response (CR) of the 75 dB group was severely
      impaired, whereas the CR of the 100 dB group exhibited no significant change
      relative to the control. When muscimol was administered 4 weeks after tEBC
      acquisition, the CR was impaired in both the 75 dB and 100 dB groups. This study
      indicate that the cACC of the mPFC is necessary for recent retrieval of tEBC with
      a low-intensity CS but not of tEBC with a high-intensity CS, whereas for remote
      retrieval of tEBC, the cACC of the mPFC is essential regardless of whether the CS
      intensity is high or low. These results support a conditional role for the mPFC
      in modulating recent retrieval of tEBC and a persistent role for its involvement
      in remote retrieval of tEBC.

PMID- 29370237
TI  - Increased separase activity and occurrence of centrosome aberrations concur with
      transformation of MDS.
AB  - ESPL1/separase, a cysteine endopeptidase, is a key player in centrosome
      duplication and mitotic sister chromatid separation. Aberrant expression and/or
      altered separase proteolytic activity are associated with centrosome
      amplification, aneuploidy, tumorigenesis and disease progression. Since
      centrosome alterations are a common and early detectable feature in patients with
      myelodysplastic syndrome (MDS) and cytogenetic aberrations play an important role
      in disease risk stratification, we examined separase activity on single cell
      level in 67 bone marrow samples obtained from patients with MDS, secondary acute
      myeloid leukemia (sAML), de novo acute myeloid leukemia (AML) and healthy
      controls by a flow cytometric separase activity assay. The separase activity
      distribution (SAD) value, a calculated measure for the occurrence of cells with
      prominent separase activity within the analyzed sample, was tested for
      correlation with the centrosome, karyotype and gene mutation status. We found
      higher SAD values in bone marrow cells of sAML patients than in corresponding
      cells of MDS patients. This concurred with an increased incidence of aberrant
      centrosome phenotypes in sAML vs. MDS samples. No correlation was found between
      SAD values and the karyotype/gene mutation status. During follow-up of four MDS
      patients we observed increasing SAD values after transformation to sAML, in two
      patients SAD values decreased during azacitidine therapy. Cell culture
      experiments employing MDS-L cells as an in vitro model of MDS revealed that
      treatment with rigosertib, a PLK1 inhibitor and therapeutic drug known to induce
      G2/M arrest, results in decreased SAD values. In conclusion, the appearance of
      cells with unusual high separase activity levels, as indicated by increased SAD
      values, concurs with the transformation of MDS to sAML and may reflect separase
      dysregulation potentially contributing to clonal evolution during MDS
      progression. Separase activity measurement may therefore be useful as a novel
      additional molecular marker for disease monitoring.

PMID- 29370236
TI  - Ethyl pyruvate inhibits oxidation of LDL in vitro and attenuates oxLDL toxicity
      in EA.hy926 cells.
AB  - BACKGROUND: Ethyl pyruvate (EP) exerts anti-inflammatory and anti-oxidative
      properties. The aim of our study was to investigate whether EP is capable of
      inhibiting the oxidation of LDL, a crucial step in atherogenesis. Additionally,
      we examined whether EP attenuates the cytotoxic effects of highly oxidized LDL in
      the human vascular endothelial cell line EA.hy926. METHODS: Native LDL (nLDL) was
      oxidized using Cu2+ ions in the presence of increasing amounts of EP. The degree
      of LDL oxidation was quantified by measuring lipid hydroperoxide (LPO) and
      malondialdehyde (MDA) concentrations, relative electrophoretic mobilities (REMs),
      and oxidation-specific immune epitopes. The cytotoxicity of these oxLDLs on
      EA.hy926 cells was assessed by measuring cell viability and superoxide levels.
      Furthermore, the cytotoxicity of highly oxidized LDL on EA.hy926 cells under
      increasing concentrations of EP in the media was assessed including measurements
      of high energy phosphates (ATP). RESULTS: Oxidation of nLDL using Cu2+ ions was
      remarkably inhibited by EP in a concentration-dependent manner, reflected by
      decreased levels of LPO, MDA, REM, oxidation-specific epitopes, and diminished
      cytotoxicity of the obtained oxLDLs in EA.hy926 cells. Furthermore, the
      cytotoxicity of highly oxidized LDL on EA.hy926 cells was remarkably attenuated
      by EP added to the media in a concentration-dependent manner reflected by a
      decrease in superoxide and an increase in viability and ATP levels. CONCLUSIONS:
      EP has the potential for an anti-atherosclerotic drug by attenuating both, the
      oxidation of LDL and the cytotoxic effect of (already formed) oxLDL in EA.hy926
      cells. Chronic administration of EP might be beneficial to impede the development
      of atherosclerotic lesions.

PMID- 29370238
TI  - The existence of fertile hybrids of closely related model earthworm species,
      Eisenia andrei and E. fetida.
AB  - Lumbricid earthworms Eisenia andrei (Ea) and E. fetida (Ef) are simultaneous
      hermaphrodites with reciprocal insemination capable of self-fertilization while
      the existence of hybridization of these two species was still debatable. During
      the present investigation fertile hybrids of Ea and Ef were detected. Virgin
      specimens of Ea and Ef were laboratory crossed (Ea+Ef) and their progeny was
      doubly identified. 1 -identified by species-specific maternally derived haploid
      mitochondrial DNA sequences of the COI gene being either 'a' for worms hatched
      from Ea ova or 'f' for worms hatched from Ef ova. 2 -identified by the diploid
      maternal/paternal nuclear DNA sequences of 28s rRNA gene being either 'AA' for
      Ea, 'FF' for Ef, or AF/FA for their hybrids derived either from the 'aA' or 'fF'
      ova, respectively. Among offspring of Ea+Ef pairs in F1 generation there were
      mainly aAA and fFF earthworms resulted from the facilitated self-fertilization
      and some aAF hybrids from aA ova but none fFA hybrids from fF ova. In F2
      generation resulting from aAF hybrids mated with aAA a new generations of aAA and
      aAF hybrids were noticed, while aAF hybrids mated with fFF gave fFF and both aAF
      and fFA hybrids. Hybrids intercrossed together produced plenty of cocoons but no
      hatchlings independently whether aAF+aAF or aAF+fFA were mated. These results
      indicated that Ea and Ef species, easy to maintain in laboratory and commonly
      used as convenient models in biomedicine and ecotoxicology, may also serve in
      studies on molecular basis of interspecific barriers and mechanisms of
      introgression and speciation. Hypothetically, their asymmetrical hybridization
      can be modified by some external factors.

PMID- 29370239
TI  - Microbiological characteristics of a novel species most closely related to
      'Bergeyella cardium' as a pathogen of infectious endocarditis.
AB  - Infectious endocarditis (IE) can be caused by various pathogens, from dominating
      agents such as viridans group streptococci and staphylococci to rare species that
      are less virulent and not typically considered to be pathogens. In this study, we
      have isolated a novel species from a patient with problem of IE which was
      genetically most closely related to 'Bergeyella cardium', a causative pathogen of
      IE first reported in Korea in 2015 as a new species of the genus Bergeyella, with
      a similarity of 98.8% in 16S rRNA sequences. Microbiological characteristics,
      including morphology, biochemical identification and antimicrobial susceptibility
      profiling, of this novel species were determined. This fastidious Gram-negative
      bacillus could only be identified successfully by molecular sequencing analysis
      at present, and it exhibited low minimum inhibitory concentrations to the
      antibiotics tested except for aminoglycosides. Phylogeny analysis revealed this
      novel species clustered well with 'B. cardium' and other close species of genus
      Bergeyella.

PMID- 29370240
TI  - A histological examination of spinal reconstruction using a frozen bone
      autograft.
AB  - Our aim was to compare the process of bone formation after reconstruction of the
      vertebral body using a titanium cage with either a liquid nitrogen-treated
      (frozen) bone autograft or non-treated fresh bone autograft. Twelve canine
      beagles underwent anterior reconstruction of the 5th lumbar vertebrae using a
      titanium cage and bone autograft. Bone formation was compared across four
      experimental groups: fresh bone autograft groups, with animals sacrificed at
      either 8 or 16 weeks post-reconstruction, and liquid nitrogen-treated (frozen)
      bone autograft groups, with animals again sacrificed at either 8 or 16 weeks post
      reconstruction. Bone formation was evaluated histologically by calculating the
      proportion of 'reaction' and 'mature bone' regions at the ends of the cage, its
      center, and ventral/dorsal sides. The reaction region contained osteocytes with a
      nucleus and osteoblasts accumulated on the surface of an osteoid, while a laminar
      structure was visible for mature bone regions. For fresh bone autografts, the
      reaction and mature bone regions significantly increased from 8 to 16 weeks post
      reconstruction. By comparison, for frozen autografts, the reaction bone region
      did not significantly increase from 8 to 16 weeks post-reconstruction, while the
      mature bone region did increase over this time period. The proportion of reaction
      bone was higher at the ends and dorsal side of the cage at 8 weeks, for both
      graft types, with greater bone formation at the center of the cage at 16 weeks
      only for the fresh bone autograft. Therefore, bone formation in the anterior
      spinal reconstruction site tended to be delayed when using a frozen bone
      autograft compared to a fresh bone autograft. The bone formation process,
      however, was similar for both groups, beginning at the ends and dorsal side of
      the cage adjacent to the surrounding vertebral bone.

PMID- 29370241
TI  - Is gingival bleeding a symptom of type 2 and 3 von Willebrand disease?
AB  - BACKGROUND: Von Willebrand disease (VWD) is the most common inherent bleeding
      disorder. Gingival bleeding is a frequently reported symptom of VWD. However,
      gingival bleeding is also a leading symptom of plaque-induced gingivitis and
      untreated periodontal disease. In type 1 VWD gingival bleeding was not increased
      compared to controls. Thus, this study evaluated whether type 2 and 3 VWD
      determines an increased susceptibility to gingival bleeding in response to the
      oral biofilm. METHODS: Twenty-four cases and 24 controls matched for age, sex,
      periodontal diagnosis, number of teeth and smoking were examined hematologically
      (VWF antigen, VWF activity, factor VIII activity) and periodontally (Gingival
      Bleeding Index [GBI]), bleeding on probing [BOP], Plaque Control Record [PCR],
      periodontal inflamed surface area [PISA], vertical probing attachment level).
      RESULTS: BOP (VWD: 14.5+/-10.1%; controls: 12.3+/-5.3%; p = 0.542) and GBI (VWD:
      10.5+/-9.9%; controls: 8.8+/-4.8%; p = 0.852) were similar for VWD and controls.
      Multiple regressions identified female sex, HbA1c, PCR and PISA to be associated
      with BOP. HbA1c and PCR were associated with GBI. Number of remaining teeth was
      negatively correlated with BOP and GBI. CONCLUSION: Type 2 and 3 VWD are not
      associated with a more pronounced inflammatory response to the oral biofilm in
      terms of BOP and GBI.

PMID- 29370242
TI  - Trapping or tethering stones (TS): A multifunctional device in the Pastoral
      Neolithic of the Sahara.
AB  - The Pierres de Ben Barour, also known as trapping or tethering stones (TS), are
      stone artefacts with notches or grooves usually interpreted as hunting devices on
      the basis of rock art engravings. Though their presence is a peculiar feature of
      desert landscapes from the Sahara to the Arabian Peninsula, we know little about
      their age, context and function. Here we present a new approach to the study of
      these artefacts based on a large dataset (837 items) recorded in the Messak
      plateau (SW Libya). A statistically-based geoarchaeological survey carried out
      between 2007 and 2011 in Libya, alongside landscape and intra-site analyses of
      specific archaeological features (such as rock art, settlement and ceremonial
      contexts), reveal that these artefacts were used for a prolonged period, probably
      from the early Holocene. This was followed by a multifunctional use of these
      devices, particularly during the Pastoral Neolithic phase (ca. 6400-3000 cal BC),
      with the highest concentrations being found near ceremonial contexts related to
      cattle burials.

PMID- 29370244
TI  - Acute ingestion of beetroot juice increases exhaled nitric oxide in healthy
      individuals.
AB  - BACKGROUND AND OBJECTIVE: Nitric oxide (NO) plays an important role in the
      airways' innate immune response, and the fraction of exhaled NO at a flow rate of
      50mL per second (FENO50) has been utilized to capture NO. Deficits in NO are
      linked to loss of bronchoprotective effects in airway challenges and predict
      symptoms of respiratory infection. While beetroot juice supplements have been
      proposed to enhance exercise performance by increasing dietary nitrate
      consumption, few studies have examined the impact of beetroot juice or nitrate
      supplementation on airway NO in contexts beyond an exercise challenge, which we
      know influences FENO50. METHODS: We therefore examined the influence of a
      beetroot juice supplement on FENO50 in healthy males and females (n = 38) during
      periods of rest and in normoxic conditions. FENO50, heart rate, blood pressure,
      and state affect were measured at baseline, 45 minutes, and 90 minutes following
      ingestion of 70ml beetroot juice (6.5 mmol nitrate). Identical procedures were
      followed with ingestion of 70ml of water on a control day. RESULTS: After
      beetroot consumption, average values of the natural log of FENO50 (lnFENO50)
      increased by 21.3% (Cohen's d = 1.54, p < .001) 45 minutes after consumption and
      by 20.3% (Cohen's d = 1.45, p < .001) 90 min after consumption. On the other
      hand, only very small increases in FENO50 were observed after consumption of the
      control liquid (less than 1% increase). A small subset (n = 4) of participants
      completed an extended protocol lasting over 3 hours, where elevated levels of
      FENO50 persisted. No significant changes in cardiovascular measures were observed
      with this small single dose of beetroot juice. CONCLUSION: As NO serves a key
      role in innate immunity, future research is needed to explore the potential
      clinical utility of beetroot and dietary nitrate to elevate FENO50 and prevent
      respiratory infection.

PMID- 29370243
TI  - Inhibition of EV71 by curcumin in intestinal epithelial cells.
AB  - EV71 is a positive-sense single-stranded RNA virus that belongs to the
      Picornaviridae family. EV71 infection may cause various symptoms ranging from
      hand-foot-and-mouth disease to neurological pathological conditions such as
      aseptic meningitis, ataxia, and acute transverse myelitis. There is currently no
      effective treatment or vaccine available. Various compounds have been examined
      for their ability to restrict EV71 replication. However, most experiments have
      been performed in rhabdomyosarcoma or Vero cells. Since the gastrointestinal
      tract is the entry site for this pathogen, we anticipated that orally ingested
      agents may exert beneficial effects by decreasing virus replication in intestinal
      epithelial cells. In this study, curcumin (diferuloylmethane, C21H20O6), an
      active ingredient of turmeric (Curcuma longa Linn) with anti-cancer properties,
      was investigated for its anti-enterovirus activity. We demonstrate that curcumin
      treatment inhibits viral translation and increases host cell viability. Curcumin
      does not exert its anti-EV71 effects by modulating virus attachment or virus
      internal ribosome entry site (IRES) activity. Furthermore, curcumin-mediated
      regulation of mitogen-activated protein kinase (MAPK) signaling pathways is not
      involved. We found that protein kinase C delta (PKCdelta) plays a role in virus
      translation in EV71-infected intestinal epithelial cells and that curcumin
      treatment decreases the phosphorylation of this enzyme. In addition, we show
      evidence that curcumin also limits viral translation in differentiated human
      intestinal epithelial cells. In summary, our data demonstrate the anti-EV71
      properties of curcumin, suggesting that ingestion of this phytochemical may
      protect against enteroviral infections.

PMID- 29370245
TI  - Metamaterial-based transmit and receive system for whole-body magnetic resonance
      imaging at ultra-high magnetic fields.
AB  - Magnetic resonance imaging (MRI) at ultra-high fields (UHF), such as 7 T,
      provides an enhanced signal-to-noise ratio and has led to unprecedented high
      resolution anatomic images and brain activation maps. Although a variety of radio
      frequency (RF) coil architectures have been developed for imaging at UHF
      conditions, they usually are specialized for small volumes of interests (VoI). So
      far, whole-body coil resonators are not available for commercial UHF human whole
      body MRI systems. The goal of the present study was the development and
      validation of a transmit and receive system for large VoIs that operates at a 7 T
      human whole-body MRI system. A Metamaterial Ring Antenna System (MRAS) consisting
      of several ring antennas was developed, since it allows for the imaging of
      extended VoIs. Furthermore, the MRAS not only requires lower intensities of the
      irradiated RF energy, but also provides a more confined and focused injection of
      excitation energy on selected body parts. The MRAS consisted of several antennas
      with 50 cm inner diameter, 10 cm width and 0.5 cm depth. The position of the
      rings was freely adjustable. Conformal resonant right-/left-handed metamaterial
      was used for each ring antenna with two quadrature feeding ports for RF power.
      The system was successfully implemented and demonstrated with both a silicone oil
      and a water-NaCl-isopropanol phantom as well as in vivo by acquiring whole-body
      images of a crab-eating macaque. The potential for future neuroimaging
      applications was demonstrated by the acquired high-resolution anatomic images of
      the macaque's head. Phantom and in vivo measurements of crab-eating macaques
      provided high-resolution images with large VoIs up to 40 cm in xy-direction and
      45 cm in z-direction. The results of this work demonstrate the feasibility of the
      MRAS system for UHF MRI as proof of principle. The MRAS shows a substantial
      potential for MR imaging of larger volumes at 7 T UHF. This new technique may
      provide new diagnostic potential in spatially extended pathologies such as
      searching for spread-out tumor metastases or monitoring systemic inflammatory
      processes.

PMID- 29370246
TI  - Enhancement of muscle and locomotor performance by a series compliance: A
      mechanistic simulation study.
AB  - The objective was to better understand how a series compliance alters contraction
      kinetics and power output of muscle to enhance the work done on a load. A
      mathematical model was created in which a gravitational point load was connected
      via a linear spring to a muscle (based on the contractile properties of the
      sartorius of leopard frogs, Rana pipiens). The model explored the effects of load
      mass, tendon compliance, and delay between onset of contraction and release of
      the load (catch) on lift height and power output as measures of performance.
      Series compliance resulted in increased lift height over a relatively narrow
      range of compliances, and the effect was quite modest without an imposed catch
      mechanism unless the load was unrealistically small. Peak power of the muscle
      tendon complex could be augmented up to four times that produced with a muscle
      alone, however, lift height was not predicted by peak power. Rather, lift height
      was improved as a result of the compliance synchronizing the time courses of
      muscle force and shortening velocity, in particular by stabilizing shortening
      velocity such that muscle power was sustained rather than rising and immediately
      falling. With a catch mechanism, enhanced performance resulted largely from
      energy storage in the compliance during the period of catch, rather than
      increased time for muscle activation before movement commenced. However, series
      compliance introduced a trade-off between work done before versus after release
      of the catch. Thus, the ability of tendons to enhance locomotor performance (i.e.
      increase the work done by muscle) appears dependent not only on their established
      role in storing energy and increasing power, but also on their ability to
      modulate the kinetics of muscle contraction such that power is sustained over
      more of the contraction, and maximizing the balance of work done before versus
      after release of a catch.

PMID- 29370247
TI  - Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and
      cytokines from whole blood using CytoSorb(r) sorbent porous polymer beads.
AB  - OBJECTIVE: Sepsis is defined as life-threatening organ dysfunction caused by a
      dysregulated host response to infection. In sepsis and septic shock, pathogen
      associated molecular pattern molecules (PAMPS), such as bacterial exotoxins,
      cause direct cellular damage and/or trigger an immune response in the host often
      leading to excessive cytokine production, a maladaptive systemic inflammatory
      response syndrome response (SIRS), and tissue damage that releases DAMPs, such as
      activated complement and HMGB-1, into the bloodstream causing further organ
      injury. Cytokine reduction using extracorporeal blood filtration has been
      correlated with improvement in survival and clinical outcomes in experimental
      studies and clinical reports, but the ability of this technology to reduce a
      broader range of inflammatory mediators has not been well-described. This study
      quantifies the size-selective adsorption of a wide range of sepsis-related
      inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single
      compartment, in vitro whole blood recirculation system. MEASUREMENTS AND MAIN
      RESULTS: Purified proteins were added to whole blood at clinically relevant
      concentrations and recirculated through a device filled with CytoSorb(r)
      hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead)
      device in vitro. Except for the TNF-alpha trimer, hemoadsorption through porous
      polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS,
      PAMPS and mycotoxins by more than 50 percent. CONCLUSIONS: This study
      demonstrates that CytoSorb(r) hemoadsorbent polymer beads efficiently remove a
      broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means
      of reducing the uncontrolled inflammatory cascade that contributes to a
      maladaptive SIRS response, organ dysfunction and death in patients with a broad
      range of life-threatening inflammatory conditions such as sepsis, toxic shock
      syndrome, necrotizing fasciitis, and other severe inflammatory conditions.

PMID- 29370248
TI  - Globally fixed-time synchronization of coupled neutral-type neural network with
      mixed time-varying delays.
AB  - This paper mainly studies the globally fixed-time synchronization of a class of
      coupled neutral-type neural networks with mixed time-varying delays via
      discontinuous feedback controllers. Compared with the traditional neutral-type
      neural network model, the model in this paper is more general. A class of general
      discontinuous feedback controllers are designed. With the help of the definition
      of fixed-time synchronization, the upper right-hand derivative and a defined
      simple Lyapunov function, some easily verifiable and extensible synchronization
      criteria are derived to guarantee the fixed-time synchronization between the
      drive and response systems. Finally, two numerical simulations are given to
      verify the correctness of the results.

PMID- 29370249
TI  - Extra vitamin D from fortification and the risk of preeclampsia: The D-tect
      Study.
AB  - The objective of the study was to examine if exposure to extra vitamin D from
      food fortification was associated with a decrease in the risk of preeclampsia.
      The study was based on a natural experiment exploring the effect of the abolition
      of the Danish mandatory vitamin D fortification of margarine in 1985. The effect
      of the extra vitamin D (1.25MUg vitamin D/100 g margarine) was examined by
      comparing preeclampsia risk in women who have been exposed or unexposed to extra
      vitamin D from the fortified margarine during pregnancy, and who gave birth in
      the period from June 1983 to August 1988. The Danish National Patient Registry
      allowed the identification of pregnancies complicated by preeclampsia. The study
      included 73,237 women who gave birth during 1983-1988. We found no association
      between exposure to vitamin D fortification during pregnancy and the risk of any
      of the pregnancy related hypertensive disorders, including preeclampsia: Odds
      ratios (OR, 95%) for all hypertensive pregnancy related disorders among exposed
      vs. unexposed women was (OR 1.04, 95%CI: 0.98,1.10). In conclusion, the extra
      vitamin D from the mandatory vitamin D fortification did not influence the risk
      of preeclampsia.

PMID- 29370250
TI  - Associations of psychosocial factors with pregnancy healthy life styles.
AB  - Healthy behaviors in pregnant women have a major effect on pregnancy outcomes;
      however, only few studies have explored the relationship of multiple psychosocial
      factors with healthy lifestyles during pregnancy. The objective of this study was
      to investigate whether the five psychosocial factors of anxiety, stress,
      depression, marital dissatisfaction, and social support are associated with six
      domains of healthy lifestyles in pregnant women, including nutrition, physical
      activity, health responsibility, stress management, interpersonal relationships,
      and self-actualization. In this cross-sectional study, 445 pregnant women from
      the obstetrics clinics of the teaching hospitals of Babol University of Medical
      Sciences were included. The subjects answered six questionnaires, including the
      Health-Promoting Lifestyle Profile, Beck Depression Inventory, Prenatal Distress
      Questionnaire, State-Trait Anxiety Inventory, Social Support Questionnaire, and
      Marital Satisfaction Scale. We developed a series of simple linear regression
      models based on each subscale of lifestyle (nutrition, physical activity, health
      responsibility, stress management, interpersonal relationships, and self
      actualization) as the dependent variables and the five psychological variables
      (anxiety, stress, depression, marital dissatisfaction, and social support) as the
      independent variables. State and trait anxieties were the strongest negative
      predictors of all aspects of a healthy lifestyle. Furthermore, depression was
      negatively associated with all of the six subscales of a healthy lifestyle.
      Pregnancy-specific stress was the only negative predictor of stress management
      and self-actualization. Marital dissatisfaction was negatively associated with
      nutrition, stress management, health responsibility, and self-actualization.
      Social support had negative and positive associations with healthy behaviors. The
      study suggests that more attention should be paid to identifying the
      psychological risk factors in pregnancy in addition to providing suitable
      interventions for improving the lifestyle of pregnant women.

PMID- 29370251
TI  - Improving generation length estimates for the IUCN Red List.
AB  - The International Union for the Conservation of Nature (IUCN) Red List classifies
      species according to their risk of extinction, informing local to global
      conservation decisions. Here we look to advance the estimation of generation
      length, which is used as a time-scalar in the Red List as a way of accounting for
      differences in species' life-histories. We calculated or predicted generation
      length for 86 species of antelope following the Rspan approach. We also tested
      the importance of both allometry (body-mass) and phylogeny (phylogenetic
      eigenvectors) as predictors of generation length within a Phylogenetic
      Eigenvector Map (PEM) framework. We then evaluated the predictive power of this
      PEM and two binning approaches, following a leave-one-out cross-validation
      routine. We showed that captive and wild longevity data are nonequivalent and
      that both body-mass and phylogeny are important predictors for generation length
      (body-mass explained 64% and phylogeny 36% of the partitioned explained
      variance). Plus, both the PEM, and the binning approach that included both
      taxonomic rank and body-mass, had good predictive power and therefore are
      suitable for extrapolating generation length to missing-data species. Therefore,
      based on our findings, we advise separating captive and wild data when estimating
      generation length, and considering the implications of wild and captive data more
      widely in life-history analyses. We also recommend that body-mass and phylogeny
      should be used in combination, preferably under a PEM framework (as it was less
      reliant on available reference species and more explicitly accounts for
      phylogenetic relatedness) or a binning approach if a PEM is not feasible, to
      extrapolate generation length to missing-data species. Overall, we provide a
      transparent, consistent and transferable workflow for improving the use of the
      Rspan method to calculate generation length for the IUCN Red List.

PMID- 29370252
TI  - The modulating effect of education on semantic interference during healthy aging.
AB  - Aging has traditionally been related to impairments in name retrieval. These
      impairments have usually been explained by a phonological transmission deficit
      hypothesis or by an inhibitory deficit hypothesis. This decline can, however, be
      modulated by the educational level of the sample. This study analyzed the
      possible role of these approaches in explaining both object and face naming
      impairments during aging. Older adults with low and high educational level and
      young adults with high educational level were asked to repeatedly name objects or
      famous people using the semantic-blocking paradigm. We compared naming when
      exemplars were presented in a semantically homogeneous or in a semantically
      heterogeneous context. Results revealed significantly slower rates of both face
      and object naming in the homogeneous context (i.e., semantic interference), with
      a stronger effect for face naming. Interestingly, the group of older adults with
      a lower educational level showed an increased semantic interference effect during
      face naming. These findings suggest the joint work of the two mechanisms proposed
      to explain age-related naming difficulties, i.e., the inhibitory deficit and the
      transmission deficit hypothesis. Therefore, the stronger vulnerability to
      semantic interference in the lower educated older adult sample would possibly
      point to a failure in the inhibitory mechanisms in charge of interference
      resolution, as proposed by the inhibitory deficit hypothesis. In addition, the
      fact that this interference effect was mainly restricted to face naming and not
      to object naming would be consistent with the increased age-related difficulties
      during proper name retrieval, as suggested by the transmission deficit
      hypothesis.

PMID- 29370253
TI  - In vitro antioxidant capacities of eight different kinds of apples and their
      effects on lipopolysaccharide-induced oxidative damage in mice.
AB  - In the present study, the DPPH and ABTS+ radical scavenging activity of eight
      types of apples decreased (P < 0.05) during the 70-day storage at 4 degrees C.
      The Fushi (F2) apples from Xin Jiang showed the highest radical scavenging
      activity. For in vivo study, 40 male Kunming mice (body weight 20-25 g) were
      selected and randomly assigned to four groups (10 mice per group). The F2 groups
      (F2S, F2 + sterile saline and F2L, F2 + lipopolysaccharide) were administered
      with 0.3 mL F2 filtrate via gastric intubation daily for 28 days. The control
      groups (CS, CON + sterile saline and CL, CON + lipopolysaccharide) were treated
      with sterile saline at the same volume. At day 29, mice of F2L and CL groups were
      injected with 100 MUg/kg body weight of lipopolysaccharide (LPS)
      intraperitoneally, while those of F2S and CS groups were injected equal volume of
      sterile saline. In comparison to the CS group, the CL group showed a decrease (P
      < 0.05) in serum, liver, and hepatic mitochondrial antioxidant capacity,
      reduction (P < 0.05) in the expression of hepatic antioxidant-related genes, and
      an increase (P < 0.05) in serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), malondialdehyde (MDA), protein carbonyl (PC), and
      reactive oxygen species (ROS). In comparison to the CL group, the F2L group
      showed lower (P < 0.05) levels of serum ALT, AST, and ROS, higher (P < 0.05)
      level of serum, liver, and hepatic mitochondrial antioxidant capacity, increased
      mitochondrial membrane potential (MMP), and enhanced (P < 0.05) expression of
      hepatic antioxidant-related genes. These results suggest that F2 may exert
      protective effect against LPS-induced oxidative damage by improving the
      antioxidant capacity.

PMID- 29370254
TI  - Hepatitis E prevalence in a sexual high-risk population compared to the general
      population.
AB  - Transmission routes of the hepatitis E virus (HEV) are under debate. Here, we
      studied possible sexual transmission by comparing HEV prevalence in a Dutch
      sexual high-risk population (n = 1,482) with that in a general population (n =
      1,487) while assessing sociodemographic and sexual risk factors. Overall
      prevalence of anti-HEV IgG of 18.9% (n = 562) was, adjusting for confounders,
      similar between the two populations (p = 0.44). Prevalence was higher with each
      year's increase in age (adjusted OR: 1.03, 95%CI: 1.02-1.04, p<0.01), among men
      (adjusted OR: 1.24, 95%CI: 1.02-1.50, p = 0.03) and among individuals diagnosed
      with sexually transmitted infections (adjusted OR: 1.60, 95%CI: 1.02-2.49, p =
      0.04). Our results only hint at the possibility of a sexual transmission route
      for HEV given higher rates in those with chlamydia and/or gonorrheal infections.
      Sexual transmission is not a dominant transmission route, as its prevalence was
      not higher for the sexual high-risk population than for the general population.

PMID- 29370255
TI  - Disfluent presentations lead to the creation of more false memories.
AB  - The creation of false memories within the Deese-Roediger-McDermott (DRM) paradigm
      has been shown to be sensitive to many factors such as task instructions,
      participant mood, or even presentation modality. However, do other simple
      perceptual differences also impact performance on the DRM and the creation of
      false memories? This study explores the potential impact of changes in perceptual
      disfluency on DRM performance. To test for a potential influence of disfluency on
      false memory creation, participants viewed lists under either perceptually
      disfluent conditions or not. Results indicated that disfluency did significantly
      impact performance in the DRM paradigm; more disfluent presentations
      significantly increased the recall and recognition of unpresented information,
      although they did not impact recall or recognition of presented information.
      Thus, although disfluency did impact performance, disfluency did not produce a
      positive benefit related to overall task performance. This finding instead
      suggests that more disfluent presentations can increase the likelihood that false
      memories are created, and provide little positive performance benefit.

PMID- 29370256
TI  - Effects of a brief mindfulness-meditation intervention on neural measures of
      response inhibition in cigarette smokers.
AB  - Research suggests that mindfulness-practices may aid smoking cessation. Yet, the
      neural mechanisms underlying the effects of mindfulness-practices on smoking are
      unclear. Response inhibition is a main deficit in addiction, is associated with
      relapse, and could therefore be a candidate target for mindfulness-based
      practices. The current study hence investigated the effects of a brief
      mindfulness-practice on response inhibition in smokers using behavioral and
      electroencephalography (EEG) measures. Fifty participants (33 females, mean age
      20 years old) underwent a protocol of cigarette exposure to induce craving (cue
      exposure) and were then randomly assigned to a group receiving mindfulness
      instructions or control-instructions (for 15 minutes approximately). Immediately
      after this, they performed a smoking Go/NoGo task, while their brain activity was
      recorded. At the behavioral level, no group differences were observed. However,
      EEG analyses revealed a decrease in P3 amplitude during NoGo vs. Go trials in the
      mindfulness versus control group. The lower P3 amplitude might indicate less
      effortful response inhibition after the mindfulness-practice, and suggest that
      enhanced response inhibition underlies observed positive effects of mindfulness
      on smoking behavior.

PMID- 29370257
TI  - Does ear endoscopy provide advantages in the outpatient management of open
      mastoidectomy cavities?
AB  - OBJECTIVE: To evaluate the use of ear endoscopy in the postoperative management
      of open mastoidectomy cavities, and to test whether ear endoscopy improves
      inspection and cleaning compared with ear microscopy. METHODS: Prospective study.
      Thirty-two ears were divided into two groups: group 1, examination and cleaning
      of mastoid cavities under endoscopic visualization after microscopic standard ear
      cleaning; group 2, examination and cleaning of mastoid cavities under microscopic
      visualization after endoscope-assisted ear cleaning. We assessed the ability of
      each method to provide exposure and facilitate cleaning, comparing the benefits
      of microscopy and endoscopy when used sequentially and vice-versa. RESULTS:
      Endoscopy provided additional benefits for exposure in 61.1% of cases and
      cleaning in 66.7%. Microscopy provided no additional benefits in terms of
      exposure in any case, and provided added benefit for cleaning in only 21.4% of
      cases. DISCUSSION: For outpatient postoperative care of open mastoidectomy
      cavities, ear endoscopy provides greater benefit over ear microscopy than vice
      versa. In over half of all cases, endoscopy was able to expose areas not
      visualized under the microscope. Furthermore, in two-thirds of cases, endoscopy
      enabled removal of material that could not be cleared under microscopy. Ear
      endoscopy was superior to microscopy in terms of enabling exposure and cleaning
      of hard-to-reach sites, due to its wider field of vision. CONCLUSION: Ear
      endoscopy is a feasible technique for the postoperative management of open
      mastoidectomy cavities. Ear endoscopy provided superior advantages in terms of
      exposure and aural cleaning compared with microscopy.

PMID- 29370258
TI  - Involving men to improve maternal and newborn health: A systematic review of the
      effectiveness of interventions.
AB  - BACKGROUND: Emerging evidence and program experience indicate that engaging men
      in maternal and newborn health can have considerable health benefits for women
      and children in low- and middle-income countries. Previous reviews have
      identified male involvement as a promising intervention, but with a complex
      evidence base and limited direct evidence of effectiveness for mortality and
      morbidity outcomes. OBJECTIVE: To determine the effect of interventions to engage
      men during pregnancy, childbirth and infancy on mortality and morbidity, as well
      as effects on mechanisms by which male involvement is hypothesised to influence
      mortality and morbidity outcomes: home care practices, care-seeking, and couple
      relationships. METHODS: Using a comprehensive, highly sensitive mapping of
      maternal health intervention studies conducted in low- and middle-income
      countries between 2000 and 2012, we identified interventions that have engaged
      men to improve maternal and newborn health. Primary outcomes were care-seeking
      for essential services, mortality and morbidity, and home care practices.
      Secondary outcomes relating to couple relationships were extracted from included
      studies. RESULTS: Thirteen studies from nine countries were included.
      Interventions to engage men were associated with improved antenatal care
      attendance, skilled birth attendance, facility birth, postpartum care, birth and
      complications preparedness and maternal nutrition. The impact of interventions on
      mortality, morbidity and breastfeeding was less clear. Included interventions
      improved male partner support for women and increased couple communication and
      joint decision-making, with ambiguous effects on women's autonomy. CONCLUSION:
      Interventions to engage men in maternal and newborn health can increase care
      seeking, improve home care practices, and support more equitable couple
      communication and decision-making for maternal and newborn health. These findings
      support engaging men as a health promotion strategy, although evidence gaps
      remain around effects on mortality and morbidity. Findings also indicate that
      interventions to increase male involvement should be carefully designed and
      implemented to mitigate potential harmful effects on couple relationship
      dynamics.

PMID- 29370259
TI  - Blood Urea Nitrogen (BUN) is independently associated with mortality in
      critically ill patients admitted to ICU.
AB  - PURPOSE: Blood urea nitrogen (BUN) was reported to be associated with mortality
      in heart failure patients. We aimed to evaluate admission BUN concentration in a
      heterogeneous critically ill patient collective admitted to an intensive care
      unit (ICU) for prognostic relevance. METHODS: A total of 4176 medical patients
      (67+/-13 years) admitted to a German ICU between 2004 and 2009 were included.
      Follow-up of patients was performed retrospectively between May 2013 and November
      2013. Association of admission BUN and both intra-hospital and long-term
      mortality were investigated by Cox regression. An optimal cut-off was calculated
      by means of the Youden-Index. RESULTS: Patients with higher admission BUN
      concentration were older, clinically sicker and had more pronounced laboratory
      signs of multi-organ failure including kidney failure. Admission BUN was
      associated with adverse long-term mortality (HR 1.013; 95%CI 1.012-1.014;
      p<0.001). An optimal cut-off was calculated at 28 mg/dL which was associated with
      adverse outcome even after correction for APACHE2 (HR 1.89; 95%CI 1.59-2.26;
      p<0.001), SAPS2 (HR 1.85; 95%CI 1.55-2.21; p<0.001) and several parameters
      including creatinine in an integrative model (HR 3.34; 95%CI 2.89-3.86; p<0.001).
      We matched 614 patients with admission BUN >28 mg/dL to case-controls <= 28mg/dL
      corrected for APACHE2 scores: BUN above 28 mg/dL remained associated with adverse
      outcome in a paired analysis with the difference being 5.85% (95%CI 1.23-10.47%;
      p = 0.02). CONCLUSIONS: High BUN concentration at admission was robustly
      associated with adverse outcome in critically ill patients admitted to an ICU,
      even after correction for co-founders including renal failure. BUN might
      constitute an independent, easily available and important parameter for risk
      stratification in the critically ill.

PMID- 29370260
TI  - Muscle strength and regional lean body mass influence on mineral bone health in
      young male adults.
AB  - The relationship between muscle strength and bone mineral content (BMC) and bone
      mineral density (BMD) is supposed from the assumption of the mechanical stress
      influence on bone tissue metabolism. However, the direct relationship is not well
      established in younger men, since the enhancement of force able to produce
      effective changes in bone health, still needs to be further studied. This study
      aimed to analyze the influence of muscle strength on BMC and BMD in undergraduate
      students. Thirty six men (24.9 +/- 8.6 y/o) were evaluated for regional and whole
      body composition by dual energy X-ray absorptiometry (DXA). One repetition
      maximum tests (1RM) were assessed on flat bench-press (BP), lat-pull down (LPD),
      leg-curl (LC), knee extension (KE), and leg-press 45 degrees  (LP45) exercises.
      Linear regression modelled the relationships of BMD and BMC to the regional body
      composition and 1RM values. Measurements of dispersion and error (R2adj and
      standard error of estimate (SEE)) were tested, setting rho at <=0.05. The BMD
      mean value for whole-body was 1.12+/-0.09 g/cm2 and BMC attained 2477.9 +/- 379.2
      g. The regional lean mass (LM) in upper-limbs (UL) (= 6.80+/-1.21 kg) was related
      to BMC and BMD for UL (R2adj = 0.74, p<0.01, SEE = 31.0 g and R2adj = 0.63, SEE =
      0.08 g/cm2), and LM in lower-limbs (LL) (= 19.13+/-2.50 kg) related to BMC and
      BMD for LL (R2adj = 0.68, p<0,01, SEE = 99.3 g and R2adj = 0.50, SEE = 0.20
      g/cm2). The 1RM in BP was related to BMD (R2adj = 0.51, SEE = 0.09 g/cm2), which
      was the strongest relationship among values of 1RM for men; but, 1RM on LPD was
      related to BMC (R2adj = 0.47, p<0.01, SEE = 44.6 g), and LC was related to both
      BMC (R2adj = 0.36, p<0.01, SEE = 142.0 g) and BMD (R2adj = 0.29, p<0.01, SEE =
      0.23 g/cm2). Hence, 1RM for multi-joint exercises is relevant to BMC and BMD in
      young men, strengthening the relationship between force and LM, and suggesting
      both to parametrizes bone mineral health.

PMID- 29370261
TI  - Inhaled nitric oxide and cognition in pediatric severe malaria: A randomized
      double-blind placebo controlled trial.
AB  - BACKGROUND: Severe malaria is a leading cause of acquired neurodisability in
      Africa and is associated with reduced nitric oxide (NO) bioavailability. A
      neuroprotective role for inhaled NO has been reported in animal studies, and
      administration of inhaled NO in preterm neonates with respiratory distress
      syndrome is associated with a 47% reduced risk of cognitive impairment at two
      years of age. METHODS: A randomized double-blind placebo-controlled trial of
      inhaled NO versus placebo as an adjunctive therapy for severe malaria was
      conducted in Uganda between 2011 and 2013. Children received study gas for a
      maximum 72 hours (inhaled NO, 80 parts per million; room air placebo).
      Neurocognitive testing was performed on children<5 years at 6 month follow-up.
      The neurocognitive outcomes assessed were overall cognition (a composite of fine
      motor, visual reception, receptive language, and expressive language), attention,
      associative memory, and the global executive composite. Main outcomes were
      attention, associative memory, and overall cognitive ability. RESULTS: Sixty-one
      children receiving iNO and 59 children receiving placebo were evaluated. Forty
      two children (35.0%) were impaired in at least one neurocognitive domain. By
      intention-to-treat analysis, there were no differences in unadjusted or
      unadjusted age-adjusted z-scores for overall cognition (beta (95% CI): 0.26 (
      0.19, 0.72), p = 0.260), attention (0.18 (-0.14, 0.51), p = 0.267), or memory
      (0.14 (-0.02, 0.30), p = 0.094) between groups by linear regression. Children
      receiving inhaled NO had a 64% reduced relative risk of fine motor impairment
      than children receiving placebo (relative risk, 95% CI: 0.36, 0.14-0.96) by log
      binomial regression following adjustment for anticonvulsant use. CONCLUSIONS:
      Severe malaria is associated with high rates of neurocognitive impairment.
      Treatment with inhaled NO was associated with reduced risk of fine motor
      impairment. These results need to be prospectively validated in a larger study
      powered to assess cognitive outcomes in order to evaluate whether strategies to
      increase bioavailable NO are neuroprotective in children with severe malaria.
      TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01255215.

PMID- 29370263
TI  - Correction: Mechanistic insights into the more potent effect of KP-54 compared to
      KP-10 in vivo.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0176821.].

PMID- 29370262
TI  - Metabolic alterations in the nymphal instars of Diaphorina citri induced by
      Candidatus Liberibacter asiaticus, the putative pathogen of huanglongbing.
AB  - Currently, huanglongbing is the most damaging disease of citrus causing huge
      economic losses. The disease is caused by the Gram-negative bacterium Candidatus
      Liberibacter asiaticus (CLas). The pathogen is transmitted in a persistent
      propagative circulative manner within its vector, the Asian citrus psyllid,
      Diaphorina citri. Exploring the metabolic alteration in the vector may lead to a
      better understanding of the nutritional needs of CLas and to designing an
      artificial medium for culturing the pathogen. It has been shown that the nymphal
      stages have a greater role in transmission mainly because they feed on plants
      more actively than adults. In this study, we carried out an untargeted
      comparative metabolomic analysis for healthy and CLas-infected 4th / 5th instar
      nymphs. The metabolic analysis was performed using trimethylsilylation and methyl
      chloroformate derivatization followed by Gas Chromatography-Mass Spectrometry (GC
      MS). Overall, the changes in the nymph metabolism due to the infection with CLas
      were more pronounced than in adults, as we previously published. Nymphs reared on
      CLas-infected Valencia sweet orange were higher in many metabolites, mainly those
      of the TCA cycle, C16 and C18 fatty acids, glucose, sucrose, L-proline, L-serine,
      pyroglutamic acid, saccharic acid, threonic acid and myo-inositol than those
      reared on healthy plants. In contrast, CLas-infected nymphs were lower in
      putrescine, glycine, L -phenylalanine, L -tyrosine, L -valine, and chiro
      inositol. The information provided from this study may contribute in acceleration
      of the availability of CLas in culture and consequent screening of antibacterial
      compounds to discover a definitive solution for huanglongbing.

PMID- 29370264
TI  - Demographic factors and retrieval of object and proper names after age 70.
AB  - PURPOSE: This research aimed to investigate whether demographic factors are
      similarly related to retrieval of object and proper names. METHODS: The sample
      included 5,907 individuals above age 70 who participated in the Health and
      Retirement Study between 2004 and 2012. Participants were asked to name two
      objects as well as the US President and Vice President. Latent growth curve
      models examined the associations of age, education, and self-rated health with
      baseline levels and change trajectories in retrieval. RESULTS: Age and education
      were more strongly related to retrieval of proper names than to retrieval of
      object names, both for baseline scores and for change trajectory. Similar effects
      of self-rated health emerged for both types of stimuli. CONCLUSIONS: The results
      show that examining object names and proper names together as indication of
      cognitive status in the HRS might overlook important differences between the two
      types of stimuli, in both baseline performance and longitudinal change.

PMID- 29370265
TI  - The influence of political ideology and trust on willingness to vaccinate.
AB  - In light of the increasing refusal of some parents to vaccinate children, public
      health strategies have focused on increasing knowledge and awareness based on a
      "knowledge-deficit" approach. However, decisions about vaccination are based on
      more than mere knowledge of risks, costs, and benefits. Individual decision
      making about vaccinating involves many other factors including those related to
      emotion, culture, religion, and socio-political context. In this paper, we use a
      nationally representative internet survey in the U.S. to investigate socio
      political characteristics to assess attitudes about vaccination. In particular,
      we consider how political ideology and trust affect opinions about vaccinations
      for flu, pertussis, and measles. Our findings demonstrate that ideology has a
      direct effect on vaccine attitudes. In particular, conservative respondents are
      less likely to express pro-vaccination beliefs than other individuals.
      Furthermore, ideology also has an indirect effect on immunization propensity. The
      ideology variable predicts an indicator capturing trust in government medical
      experts, which in turn helps to explain individual-level variation with regards
      to attitudes about vaccine choice.

PMID- 29370266
TI  - Increased parietal circuit-breaker activity in delta frequency band and abnormal
      delta/theta band connectivity in salience network in hyperacusis subjects.
AB  - Recent studies have suggested that hyperacusis, an abnormal hypersensitivity to
      ordinary environmental sounds, may be characterized by certain resting-state
      cortical oscillatory patterns, even with no sound stimulus. However, previous
      studies are limited in that most studied subjects with other comorbidities that
      may have affected cortical activity. In this regard, to assess ongoing cortical
      oscillatory activity in idiopathic hyperacusis patients with no comorbidities, we
      compared differences in resting-state cortical oscillatory patterns between five
      idiopathic hyperacusis subjects and five normal controls. The hyperacusis group
      demonstrated significantly higher electrical activity in the right auditory
      related cortex for the gamma frequency band and left superior parietal lobule
      (SPL) for the delta frequency band versus the control group. The hyperacusis
      group also showed significantly decreased functional connectivity between the
      left auditory cortex (AC) and left orbitofrontal cortex (OFC), between the left
      AC and left subgenual anterior cingulate cortex (sgACC) for the gamma band, and
      between the right insula and bilateral dorsal anterior cingulate cortex (dACC)
      and between the left AC and left sgACC for the theta band versus the control
      group. The higher electrical activity in the SPL may indicate a readiness of
      "circuit-breaker" activity to shift attention to forthcoming sound stimuli. Also,
      because of the disrupted salience network, consisting of the dACC and insula,
      abnormally increased salience to all sound stimuli may emerge, as a consequence
      of decreased top-down control of the AC by the dACC and dysfunctional emotional
      weight attached to auditory stimuli by the OFC. Taken together, abnormally
      enhanced attention and salience to forthcoming sound stimuli may render
      hyperacusis subjects hyperresponsive to non-noxious auditory stimuli.

PMID- 29370267
TI  - Obesity induced alterations in redox homeostasis and oxidative stress are present
      from an early age.
AB  - OBJECTIVES: Oxidative stress and inflammation have been postulated as underlying
      mechanisms for the development of obesity-related insulin resistance. This
      association however, remains elusive especially in childhood. We sought to
      investigate this relation by measuring oxidative stress and antioxidant response
      biomarkers, before and during an oral glucose tolerance test (OGTT), in different
      biological samples from obese children. SUBJECTS: 24 children were recruited for
      the study, (18 obese and 6 controls). After OGTT, the obese group was subdivided
      in two, according to whether or not carbohydrate metabolic impairment (Ob.IR+,
      Ob.IR-; respectively) was found. Different biomarkers were analyzed after fasting
      (T = 0) and during an OGTT (T = 60 and 120 min). Lipoperoxides were measured in
      plasma, erythrocytes, and urine; while advanced glycation end products were
      determined in plasma, and redox status (GSH/GSSG ratio) in erythrocytes. RESULTS:
      We found marked differences in the characterization of the oxidative status in
      urine and erythrocytes, and in the dynamics of the antioxidant response during
      OGTT. Specifically, Ob.IR+ children show increased oxidative stress, deficient
      antioxidant response and a significant imbalance in redox status, in comparison
      to controls and Ob.IR- children. CONCLUSION: Obese children with insulin
      resistance show increased levels of oxidative stress biomarkers, and a stunted
      antioxidant response to an OGTT leading to increased oxidative stress after a
      single glucose load, as detected in erythrocytes, but not in plasma. We propose
      erythrocytes as sensors of early and acute changes in oxidative stress associated
      with insulin resistance in childhood obesity. This is a pilot study, performed
      with a limited sample size, so data should be interpreted with caution until
      reproduced.

PMID- 29370268
TI  - Circulating, cell-free DNA as a marker for exercise load in intermittent sports.
AB  - BACKGROUND: Attempts to establish a biomarker reflecting individual player load
      in intermittent sports such as football have failed so far. Increases in
      circulating DNA (cfDNA) have been demonstrated in various endurance sports
      settings. While it has been proposed that cfDNA could be a suitable marker for
      player load in intermittent sports, the effects on cfDNA of repeated sprinting as
      an essential feature in intermittent sports are unknown. For the first time, we
      assessed both alterations of cfDNA due to repeated maximal sprints and due to a
      professional football game. METHODS: Nine participants were subjected to a
      standardised sprint training session with cross-over design of five maximal
      sprints of 40 meters with either "short" (1 minute) or "long" pauses (5 minutes).
      Capillary cfDNA and lactate were measured after every sprint and venous cfDNA
      before and after each series of sprints. Moreover, capillary cfDNA and lactate
      values were taken in 23 professional football players before and after
      incremental exercise testing, during the course of a training week at rest
      (baseline) and in all 17 enrolled players following a season game. RESULTS:
      Lactate and venous cfDNA increased more pronounced during "short" compared to
      "long" (1.4-fold, p = 0.032 and 1.7-fold, p = 0.016) and cfDNA correlated
      significantly with lactate (r = 0.69; p<0.001). Incremental exercise testing
      increased cfDNA 7.0-fold (p<0.001). The season game increased cfDNA 22.7-fold
      (p<0.0001), while lactate showed a 2.0-fold (p = 0.09) increase compared to
      baseline. Fold-changes in cfDNA correlated with distance covered during game
      (spearman's r = 0.87, p = 0.0012), while no correlation between lactate and the
      tracking data could be found. DISCUSSION: We show for the first time that cfDNA
      could be an objective marker for distance covered in elite intermittent sports.
      In contrast to the potential of more established blood-based markers like IL-6,
      CK, or CRP, cfDNA shows by far the strongest fold-change and a high correlation
      with a particular load related aspect in professional football.

PMID- 29370269
TI  - The histone demethylase LSD1 regulates inner ear progenitor differentiation
      through interactions with Pax2 and the NuRD repressor complex.
AB  - The histone demethylase LSD1 plays a pivotal role in cellular differentiation,
      particularly in silencing lineage-specific genes. However, little is known about
      how LSD1 regulates neurosensory differentiation in the inner ear. Here we show
      that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD
      co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal
      progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element
      reporter were GFP-negative when untreated, but became GFP positive after forced
      differentiation or treatment with a potent LSD inhibitor. Pharmacological
      inhibition of LSD1 activity resulted in the enrichment of mono- and di
      methylation of H3K4, upregulation of sensory neuronal genes and an increase in
      the number of sensory neurons in mouse inner ear organoids. Together, these
      results identify the LSD1/NuRD complex as a previously unrecognized modulator for
      Pax2-mediated neuronal differentiation in the inner ear.

PMID- 29370270
TI  - Taxonomically-linked growth phenotypes during arsenic stress among arsenic
      resistant bacteria isolated from soils overlying the Centralia coal seam fire.
AB  - Arsenic (As), a toxic element, has impacted life since early Earth. Thus,
      microorganisms have evolved many As resistance and tolerance mechanisms to
      improve their survival outcomes given As exposure. We isolated As resistant
      bacteria from Centralia, PA, the site of an underground coal seam fire that has
      been burning since 1962. From a 57.4 degrees C soil collected from a vent above
      the fire, we isolated 25 unique aerobic As resistant bacterial strains spanning
      seven genera. We examined their diversity, resistance gene content,
      transformation abilities, inhibitory concentrations, and growth phenotypes.
      Although As concentrations were low at the time of soil collection (2.58 ppm),
      isolates had high minimum inhibitory concentrations (MICs) of arsenate and
      arsenite (>300 mM and 20 mM respectively), and most isolates were capable of
      arsenate reduction. We screened isolates (PCR and sequencing) using 12 published
      primer sets for six As resistance genes (AsRGs). Genes encoding arsenate
      reductase (arsC) and arsenite efflux pumps (arsB, ACR3(2)) were present, and
      phylogenetic incongruence between 16S rRNA genes and AsRGs provided evidence for
      horizontal gene transfer. A detailed investigation of differences in isolate
      growth phenotypes across As concentrations (lag time to exponential growth,
      maximum growth rate, and maximum OD590) showed a relationship with taxonomy,
      providing information that could help to predict an isolate's performance given
      As exposure in situ. Our results suggest that microbiological management and
      remediation of environmental As could be informed by taxonomically-linked As
      tolerance, potential for resistance gene transferability, and the rare biosphere.

PMID- 29370271
TI  - Sero-prevalence and risk factors for hepatitis E virus infection among pregnant
      women in the Cape Coast Metropolis, Ghana.
AB  - BACKGROUND: Hepatitis E virus is an emerging infection in Africa with poor
      maternal and foetal outcomes. There is scanty data on the sero-prevalence of HEV
      infection among pregnant women in Ghana. This study highlighted the prevalence
      and risk factors associated with HEV infection among pregnant women in Cape Coast
      Metropolis, Central Region of Ghana. METHODS: A multicenter (3 selected sites)
      analytical cross sectional study involving 398 pregnant women in the Cape Coast
      metropolis was conducted. HEV (Anti-HEV IgG and Anti-HEV IgM) ELISA was
      performed. Sero-positive women had liver chemistries done and data collected on
      maternal and neonatal outcomes. Data analyses were performed using Stata version
      13 software (STATA Corp, Texas USA). RESULTS: Mean age was 28.01 (+/- 5.93)
      years. HEV sero-prevalence was 12.2% (n = 48) for IgG and 0.2% (n = 1) for IgM
      with overall of 12.3%. The odds of being HEV sero-positive for women aged 26-35
      years was 3.1 (95% CI: 1.1-8.1), p = 0.02 and >=36 years it was 10.7 (95% CI; 3.4
      33.5), p = 0.0001. Living in urban settlement was associated with lowest odds of
      HEV infection {OR 0.4 (95% CI; 0.2-0.8), p = 0.01}. Factors with no statistical
      evidence of association include main source of drinking water and history of
      blood transfusion. The sero-prevalence of HEV IgG increased progressively across
      trimesters with the highest among women in their third trimester (55.3%). None of
      the 49 HEV sero-positive women had elevated ALT level. Ten (N = 41) of the
      neonates born to sero-positive women developed jaundice in the neonatal period.
      The mean birth weight was 3.1kg (SD 0.4). CONCLUSION: HEV sero-prevalence among
      pregnant women in the Cape Coast Metropolis is high enough to deserve more
      attention than it has received so far. It is therefore important to conduct
      further research on the potential impact on maternal and neonatal mortality and
      morbidity in Ghana.

PMID- 29370272
TI  - Correction: Is serum level of CC chemokine ligand 18 a biomarker for the
      prediction of radiation induced lung toxicity (RILT)?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185350.].

PMID- 29370273
TI  - Growth performance and survival of larval Atlantic herring, under the combined
      effects of elevated temperatures and CO2.
AB  - In the coming decades, environmental change like warming and acidification will
      affect life in the ocean. While data on single stressor effects on fish are
      accumulating rapidly, we still know relatively little about interactive effects
      of multiple drivers. Of particular concern in this context are the early life
      stages of fish, for which direct effects of increased CO2 on growth and
      development have been observed. Whether these effects are further modified by
      elevated temperature was investigated here for the larvae of Atlantic herring
      (Clupea harengus), a commercially important fish species. Over a period of 32
      days, larval survival, growth in size and weight, and instantaneous growth rate
      were assessed in a crossed experimental design of two temperatures (10 degrees C
      and 12 degrees C) with two CO2 levels (400 MUatm and 900 MUatm CO2) at food
      levels mimicking natural levels using natural prey. Elevated temperature alone
      led to increased swimming activity, as well as decreased survival and
      instantaneous growth rate (Gi). The comparatively high sensitivity to elevated
      temperature in this study may have been influenced by low food levels offered to
      the larvae. Larval size, Gi and swimming activity were not affected by CO2,
      indicating tolerance of this species to projected "end of the century" CO2
      levels. A synergistic effect of elevated temperature and CO2 was found for larval
      weight, where no effect of elevated CO2 concentrations was detected in the 12
      degrees C treatment, but a negative CO2 effect was found in the 10 degrees C
      treatment. Contrasting CO2 effects were found for survival between the two
      temperatures. Under ambient CO2 conditions survival was increased at 12 degrees C
      compared to 10 degrees C. In general, CO2 effects were minor and considered
      negligible compared to the effect of temperature under these mimicked natural
      food conditions. These findings emphasize the need to include biotic factors such
      as energy supply via prey availability in future studies on interactive effects
      of multiple stressors.

PMID- 29370274
TI  - Quantitative and qualitative normative dataset for intraepidermal nerve fibers
      using skin biopsy.
AB  - BACKGROUND: Skin biopsy is the most relevant tool to diagnose small-fiber
      neuropathy. A well-documented normal dataset for intraepidermal nerve fiber in
      the distal leg is required to improve its diagnostic value. METHODS: Three
      hundred healthy subjects were enrolled in the study, after clinical and
      biological screening to exclude neurological and systemic pathologies. A distal
      leg biopsy was taken and intraepidermal nerve fiber density after protein gene
      product-9.5 immunocytochemistry with brightfield microscopy was determined.
      Morphological variations of intraepidermal nerve fibers, previously described in
      small-fiber neuropathies, were analyzed. One hundred biopsies were also analyzed
      at the ultrastructural level. FINDINGS: The median number of fibers was lower in
      men compared to women and decreased with age. Using statistical modeling taking
      into account age and gender, we calculated the 5th percentile of intraepidermal
      nerve fiber density as follows: 7.6156-0.0769 x age (years) + 1.5506 x gender
      (woman = 1; man = 0). We observed a low frequency of large swellings or
      horizontal branchings but an increasing frequency of small swellings of
      intraepidermal nerve fibers and irregular distribution along the dermal-epidermal
      junction with age. Axonal diameter of unmyelinated fibers of the papillary dermis
      did not vary with age or gender. Ultrastructural analysis also showed that fiber
      endings in close apposition to Merkel cells should not be mistaken for small
      fiber swellings. CONCLUSIONS: Our dataset allows accurate calculation of the
      normal density of intraepidermal nerve fibers for each year of age and provides
      original morphological observations that improve the diagnostic value of skin
      biopsy in the distal leg for small-fiber neuropathy.

PMID- 29370275
TI  - What does media use reveal about personality and mental health? An exploratory
      investigation among German students.
AB  - The present study aimed to investigate the relationship between personality
      traits, mental health variables and media use among German students. The data of
      633 participants were collected. Results indicate a positive association between
      general Internet use, general use of social platforms and Facebook use, on the
      one hand, and self-esteem, extraversion, narcissism, life satisfaction, social
      support and resilience, on the other hand. Use of computer games was found to be
      negatively related to these personality and mental health variables. The use of
      platforms that focus more on written interaction (Twitter, Tumblr) was assumed to
      be negatively associated with positive mental health variables and significantly
      positively with depression, anxiety, and stress symptoms. In contrast, Instagram
      use, which focuses more on photo-sharing, correlated positively with positive
      mental health variables. Possible practical implications of the present results
      for mental health, as well as the limitations of the present work are discussed.

PMID- 29370276
TI  - Does nonreproductive swarming adapt to pathogens?

PMID- 29370277
TI  - PAN-811 prevents chemotherapy-induced cognitive impairment and preserves
      neurogenesis in the hippocampus of adult rats.
AB  - Chemotherapy-induced cognitive impairment (CICI) occurs in a substantial
      proportion of treated cancer patients, with no drug currently available for its
      therapy. This study investigated whether PAN-811, a ribonucleotide reductase
      inhibitor, can reduce cognitive impairment and related suppression of
      neurogenesis following chemotherapy in an animal model. Young adult rats in Chemo
      and Chemo+PAN-811 groups received 3 intraperitoneal (i.p.) injections of
      methotrexate (MTX) and 5-fluorouracil (5-FU), and those in Saline and Saline+PAN
      811 groups received equal volumes of physiological saline at 10-day intervals.
      PAN-811 in saline was delivered through i.p. injection, 10 min following each
      saline (Saline+PAN-811 group) or MTX/5-FU (Chemo+PAN-811 group) treatment, while
      equal volumes of saline were delivered to Saline and Chemo groups. Over Days 31
      66, rats were administered tests of spatial memory, nonmatching-to-sample rule
      learning, and discrimination learning, which are sensitive to dysfunction in
      hippocampus, frontal lobe and striatum, respectively. On Day 97, neurogenesis was
      immnunohistochemically evaluated by counting doublecortin-positive (DCX+) cells
      in the dentate gyrus (DG). The results demonstrated that the Chemo group was
      impaired on the three cognitive tasks, but co-administration of PAN-811
      significantly reduced all MTX/5-FU-induced cognitive impairments. In addition,
      MTX/5-FU reduced DCX+ cells to 67% of that in Saline control rats, an effect that
      was completely blocked by PAN-811 co-administration. Overall, we present the
      first evidence that PAN-811 protects cognitive functions and preserves
      neurogenesis from deleterious effects of MTX/5-FU. The current findings provide a
      basis for rapid clinical translation to determine the effect of PAN-811 on CICI
      in human.

PMID- 29370278
TI  - Diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging
      and dynamic contrast-enhanced MRI for assessment of anal fistula activity.
AB  - OBJECTIVE: To evaluate intravoxel incoherent motion (IVIM) diffusion-weighted
      imaging (DWI) and dynamic contrast-enhanced (DCE) magnetic resonance imaging
      (MRI) sequences for quantitative characterization of anal fistula activity.
      METHODS: This retrospective study was approved by the institutional review board.
      One hundred and two patients underwent MRI for clinical suspicion of anal
      fistula. Forty-three patients with demonstrable anal fistulas met the inclusion
      criteria. Quantitative analysis included measurement of DCE and IVIM parameters.
      The reference standard was clinical activity based on medical records.
      Statistical analyses included Bayesian analysis with Markov Chain Monte Carlo,
      multivariable logistic regression, and receiver operating characteristic
      analyses. RESULTS: Brevity of enhancement, defined as the time difference between
      the wash-in and wash-out, was longer in active than inactive fistulas (p = 0.02).
      Regression coefficients of multivariable logistic regression analysis revealed
      that brevity of enhancement increased and normalized perfusion area under curve
      decreased with presence of active fistulas (p = 0.03 and p = 0.04, respectively).
      By cross-validation, a logistic regression model that included quantitative
      perfusion parameters (DCE and IVIM) performed significantly better than IVIM only
      (p < 0.001). Area under the curves for distinguishing patients with active from
      those with inactive fistulas were 0.669 (95% confidence interval [CI]: 0.500,
      0.838) for a model with IVIM only, 0.860 (95% CI: 0.742, 0.977) for a model with
      IVIM and brevity of enhancement, and 0.921 (95% CI: 0.846, 0.997) for a model
      with IVIM and all DCE parameters. CONCLUSION: The inclusion of brevity of
      enhancement measured by DCE-MRI improved assessment of anal fistula activity over
      IVIM-DWI only.

PMID- 29370279
TI  - The genetics of overwintering performance in two-year old common carp and its
      relation to performance until market size.
AB  - Using farmed common carp, we investigated the genetic background of the second
      year overwintering performance and its relation to the performance during the
      third growing season and at market size. The experimental stock was established
      by partial factorial design with a series of 4 factorial matings of 5 dams and 10
      sires each. The families were reared communally and pedigree was re-constructed
      with 93.6% success using 12 microsatellites on 2008 offspring. Three successive
      recordings (second autumn, third spring, and third autumn-market size) covering
      two periods (second overwintering, third growing season) were included. Body
      weight, Fulton's condition factor and percent muscle fat content were recorded at
      all times and headless carcass yield and fillet yield were recorded at market
      size. Specific growth rate, absolute and relative fat change and overall survival
      were calculated for each period. Heritability estimates were significantly
      different from zero and almost all traits were moderately to highly heritable (h2
      = 0.36-1.00), except survival in both periods and fat change (both patterns)
      during overwintering (h2 = 0.12-0.15). Genetic and phenotypic correlations imply
      that selection against weight loss and fat loss during overwintering is expected
      to lead to a better winter survival, together with a positive effect on growth in
      the third growing season. Interestingly, higher muscle fat content was
      genetically correlated to lower survival in the following period (rg = -0.59; 
      0.53, respectively for winter and the third summer). On the other hand, higher
      muscle fat was also genetically linked to better slaughter yields. Moreover,
      selection for higher condition factor would lead to better performance during
      winter, growing season and at market size.

PMID- 29370280
TI  - CLC-Pred: A freely available web-service for in silico prediction of human cell
      line cytotoxicity for drug-like compounds.
AB  - In silico methods of phenotypic screening are necessary to reduce the time and
      cost of the experimental in vivo screening of anticancer agents through dozens of
      millions of natural and synthetic chemical compounds. We used the previously
      developed PASS (Prediction of Activity Spectra for Substances) algorithm to
      create and validate the classification SAR models for predicting the cytotoxicity
      of chemicals against different types of human cell lines using ChEMBL
      experimental data. A training set from 59,882 structures of compounds was created
      based on the experimental data (IG50, IC50, and % inhibition values) from ChEMBL.
      The average accuracy of prediction (AUC) calculated by leave-one-out and a 20
      fold cross-validation procedure during the training was 0.930 and 0.927 for 278
      cancer cell lines, respectively, and 0.948 and 0.947 for cytotoxicity prediction
      for 27 normal cell lines, respectively. Using the given SAR models, we developed
      a freely available web-service for cell-line cytotoxicity profile prediction (CLC
      Pred: Cell-Line Cytotoxicity Predictor) based on the following structural
      formula: http://way2drug.com/Cell-line/.

PMID- 29370281
TI  - Correction: D-cycloserine improves synaptic transmission in an animal mode of
      Rett syndrome.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183026.].

PMID- 29370282
TI  - Correction: Oestrogen receptor negative early operable primary breast cancer in
      older women-Biological characteristics and long-term clinical outcome.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0188528.].

PMID- 29370283
TI  - Correction: Cytokine-induced killer cell delivery enhances the antitumor activity
      of oncolytic reovirus.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184816.].

PMID- 29370284
TI  - Correction: Biofilm imaging in porous media by laboratory X-Ray tomography:
      Combining a non-destructive contrast agent with propagation-based phase-contrast
      imaging tools.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180374.].

PMID- 29370285
TI  - Severe community-acquired pneumonia: Characteristics and prognostic factors in
      ventilated and non-ventilated patients.
AB  - BACKGROUND: Patients with severe community-acquired pneumonia (SCAP) and life
      threatening acute respiratory failure may require invasive mechanical ventilation
      (IMV). Since use of IMV is often associated with significant morbidity and
      mortality, we assessed whether patients invasively ventilated would represent a
      target population for interventions aimed at reducing mortality of SCAP. METHODS:
      We prospectively recruited consecutive patients with SCAP for 12 years. We
      assessed the characteristics and outcomes of patients invasively ventilated at
      presentation of pneumonia, compared with those without IMV, and determined the
      influence of risks factors on mortality with a multivariate weighted logistic
      regression using a propensity score. RESULTS: Among 3,719 patients hospitalized
      with CAP, 664 (18%) had criteria for SCAP, and 154 (23%) received IMV at
      presentation of pneumonia; 198 (30%) presented with septic shock. In 370 (56%)
      cases SCAP was diagnosed based solely on the presence of 3 or more IDSA/ATS minor
      criteria. Streptococcus pneumoniae was the main pathogen in both groups. The 30
      day mortality was higher in the IMV, compared to non-intubated patients (51, 33%,
      vs. 94, 18% respectively, p<0.001), and higher than that predicted by APACHE-II
      score (26%). IMV independently predicted 30-day mortality in multivariate
      analysis (adjusted odds-ratio 3.54, 95% confidence interval 1.45-8.37, p =
      0.006). Other independent predictors of mortality were septic shock, worse
      hypoxemia and increased serum potassium. CONCLUSION: Invasive mechanical
      ventilation independently predicted 30-day mortality in patients with SCAP.
      Patients invasively ventilated should be considered a different population with
      higher mortality for future clinical trials on new interventions addressed to
      improve mortality of SCAP.

PMID- 29370286
TI  - Identification of the group IIa WRKY subfamily and the functional analysis of
      GhWRKY17 in upland cotton (Gossypium hirsutum L.).
AB  - WRKY transcription factors play important roles in plant defense, stress
      response, leaf senescence, and plant growth and development. Previous studies
      have revealed the important roles of the group IIa GhWRKY genes in cotton. To
      comprehensively analyze the group IIa GhWRKY genes in upland cotton, we
      identified 15 candidate group IIa GhWRKY genes in the Gossypium hirsutum genome.
      The phylogenetic tree, intron-exon structure, motif prediction and Ka/Ks analyses
      indicated that most group IIa GhWRKY genes shared high similarity and
      conservation and underwent purifying selection during evolution. In addition, we
      detected the expression patterns of several group IIa GhWRKY genes in individual
      tissues as well as during leaf senescence using public RNA sequencing data and
      real-time quantitative PCR. To better understand the functions of group IIa
      GhWRKYs in cotton, GhWRKY17 (KF669857) was isolated from upland cotton, and its
      sequence alignment, promoter cis-acting elements and subcellular localization
      were characterized. Moreover, the over-expression of GhWRKY17 in Arabidopsis up
      regulated the senescence-associated genes AtWRKY53, AtSAG12 and AtSAG13,
      enhancing the plant's susceptibility to leaf senescence. These findings lay the
      foundation for further analysis and study of the functions of WRKY genes in
      cotton.

PMID- 29370287
TI  - The mycorrhiza-dependent defensin MtDefMd1 of Medicago truncatula acts during the
      late restructuring stages of arbuscule-containing cells.
AB  - Different symbiotic and pathogenic plant-microbe interactions involve the
      production of cysteine-rich antimicrobial defensins. In Medicago truncatula, the
      expression of four MtDefMd genes, encoding arbuscular mycorrhiza-dependent
      defensins containing an N-terminal signal peptide and exhibiting some differences
      to non-symbiotic defensins, raised over the time of fungal colonization. Whereas
      the MtDefMd1 and MtDefMd2 promoters were inactive in cells containing young
      arbuscules, cells with fully developed arbuscules displayed different levels of
      promoter activities, indicating an up-regulation towards later stages of
      arbuscule formation. MtDefMd1 and MtDefMd2 expression was absent or strongly down
      regulated in mycorrhized ram1-1 and pt4-2 mutants, known for defects in arbuscule
      branching or premature arbuscule degeneration, respectively. A ~97% knock-down of
      MtDefMd1/MtDefMd2 expression did not significantly affect arbuscule size.
      Although overexpression of MtDefMd1 in arbuscule-containing cells led to an up
      regulation of MtRam1, encoding a key transcriptional regulator of arbuscule
      formation, no morphological changes were evident. Co-localization of an MtDefMd1
      mGFP6 fusion with additional, subcellular markers revealed that this defensin is
      associated with arbuscules in later stages of their life-cycle. MtDefMd1-mGFP6
      was detected in cells with older arbuscules about to collapse, and ultimately in
      vacuolar compartments. Comparisons with mycorrhized roots expressing a tonoplast
      marker indicated that MtDefMd1 acts during late restructuring processes of
      arbuscule-containing cells, upon their transition into a post-symbiotic state.

PMID- 29370289
TI  - Correction: Involvement of phenoloxidase in browning during grinding of Tenebrio
      molitor larvae.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189685.].

PMID- 29370288
TI  - Direct comparison of the four aldehyde oxidase enzymes present in mouse gives
      insight into their substrate specificities.
AB  - Mammalian aldehyde oxidases (AOXs) are molybdo-flavoenzymes which are present in
      many tissues in various mammalian species, including humans and rodents.
      Different species contain a different number of AOX isoforms. In particular, the
      reasons why mammals other than humans express a multiplicity of tissue-specific
      AOX enzymes is unknown. In mouse, the isoforms mAOX1, mAOX3, mAOX4 and mAOX2 are
      present. We previously established a codon-optimized heterologous expression
      systems for the mAOX1-4 isoforms in Escherichia coli that gives yield to
      sufficient amounts of active protein for kinetic characterizations and sets the
      basis in this study for site-directed mutagenesis and structure-function studies.
      A direct and simultaneous comparison of the enzymatic properties and
      characteristics of the four enzymes on a larger number of substrates has never
      been performed. Here, thirty different structurally related aromatic, aliphatic
      and N-heterocyclic compounds were used as substrates, and the kinetic parameters
      of all four mAOX enzymes were directly compared. The results show that especially
      mAOX4 displays a higher substrate selectivity, while no major differences between
      mAOX1, mAOX2 and mAOX3 were identified. Generally, mAOX1 was the enzyme with the
      highest catalytic turnover for most substrates. To understand the factors that
      contribute to the substrate specificity of mAOX4, site-directed mutagenesis was
      applied to substitute amino acids in the substrate-binding funnel by the ones
      present in mAOX1, mAOX3, and mAOX2. An increase in activity was obtained by the
      amino acid exchange M1088V in the active site identified to be specific for
      mAOX4, to the amino acid identified in mAOX3.

PMID- 29370290
TI  - Incidence of venous thromboembolism in Korea from 2009 to 2013.
AB  - The incidence of venous thromboembolism (VTE) is lower in Asian populations than
      in Western populations. The objective of the present study was to evaluate the
      annual age- and sex-adjusted incidence (ASR) of VTE from 2009 to 2013 in South
      Korea. In addition, annual change in the pattern of VTE treatment during the
      study period was estimated because a new direct oral anticoagulant (DOAC) had
      become available and was covered by health insurance in Korea beginning in
      January 2013. VTE cases from 2009 to 2013 were retrospectively identified based
      on both diagnostic and medication codes of anticoagulants used for initial
      treatment using the Korean Health Insurance Review and Assessment Service (HIRA)
      databases. The incidence of VTE increased yearly. It was significantly higher in
      the older population than in the younger population, and it was higher in females
      than in males. In 2009, ASRs of VTE, deep vein thrombosis, and pulmonary embolism
      were 21.3, 8.1, and 13.2 cases per 100,000 individuals, respectively in 2009.
      These increased to 29.2, 12.7, and 16.6 cases per 100,000, respectively, in 2013.
      Prescription rates of warfarin and low-molecular-weight heparin decreased with
      the introduction of a new anticoagulant in 2013. The proportion of subjects who
      underwent mechanical procedures decreased annually. The ASR of VTE in Korea
      continuously increased from 2009 to 2013, reflecting an increased awareness and
      detection of VTE as well as improved survival of patients with cancer and other
      morbidities. Following its introduction, DOAC rapidly replaced other
      anticoagulants for the treatment of VTE.

PMID- 29370291
TI  - Why do people donate to conservation? Insights from a 'real world' campaign.
AB  - Non-governmental organisations (NGOs) play a key role in biodiversity
      conservation. The majority of these organisations rely on public donations to
      fund their activities, and therefore fundraising success is a determinant of
      conservation outcomes. In spite of this integral relationship, the key principals
      for fundraising success in conservation are still guided by expert opinion and
      anecdotal evidence, with very few quantitative studies in the literature. Here we
      assessed the behaviour of monetary donors across twenty-five different species
      focused conservation campaigns organised by an NGO conservation and environmental
      society. The Australian Geographic Society (AGS) carried out fundraising
      campaigns over a five and half year period using an identical methodology in
      thirty-four of its country-wide network of outlet shops. AGS owns and operates
      these shops that sell toys and games related to science and nature. We tested how
      the following factors influenced monetary donations from members of the public:1)
      campaign duration, 2) appeal and familiarity of species, 3) species geographic
      distribution relative to the fundraising location, 4) level of income and
      education of potential donors, 5) age and gender profile of potential donors.
      Contrary to past research, we found most of these factors did not significantly
      influence the amount of donations made to each campaign by members of the public.
      Larger animals did elicit a significantly higher amount donated per transaction
      than smaller animals, as did shops located in poorer neighbourhoods. Our study
      findings contrast with past research that has focused largely on hypothetical
      donations data collected via surveys, and demonstrates the complexity and case
      specific nature of relationships between donor characteristics and spending
      patterns. The study highlights the value of assessing real-world fundraising
      campaigns, and illustrates how collaboration between academia and NGOs could be
      used to better tailor fundraising campaigns to maximise donations from individual
      citizens.

PMID- 29370292
TI  - Correction: Combined MEK and ERK inhibition overcomes therapy-mediated pathway
      reactivation in RAS mutant tumors.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185862.].

PMID- 29370295
TI  - Correction: Cost-effectiveness of national health insurance programs in high
      income countries: A systematic review.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189173.].

PMID- 29370293
TI  - Gene expression of the two developmentally regulated dermatan sulfate epimerases
      in the Xenopus embryo.
AB  - Chondroitin sulfate (CS)/dermatan sulfate (DS) proteoglycans are abundant on the
      cell surface and in the extracellular matrix and have important functions in
      matrix structure, cell-matrix interaction and signaling. The DS epimerases 1 and
      2, encoded by Dse and Dsel, respectively, convert CS to a CS/DS hybrid chain,
      which is structurally and conformationally richer than CS, favouring interaction
      with matrix proteins and growth factors. We recently showed that Xenopus Dse is
      essential for the migration of neural crest cells by allowing cell surface CS/DS
      proteoglycans to adhere to fibronectin. Here we investigate the expression of Dse
      and Dsel in Xenopus embryos. We show that both genes are maternally expressed and
      exhibit partially overlapping activity in the eyes, brain, trigeminal ganglia,
      neural crest, adenohypophysis, sclerotome, and dorsal endoderm. Dse is
      specifically expressed in the epidermis, anterior surface ectoderm, spinal
      nerves, notochord and dermatome, whereas Dsel mRNA alone is transcribed in the
      spinal cord, epibranchial ganglia, prechordal mesendoderm and myotome. The
      expression of the two genes coincides with sites of cell differentiation in the
      epidermis and neural tissue. Several expression domains can be linked to
      previously reported phenotypes of knockout mice and clinical manifestations, such
      as the Musculocontractural Ehlers-Danlos syndrome and psychiatric disorders.

PMID- 29370294
TI  - Two closely related Rho GTPases, Cdc42 and RacA, of the en-dophytic fungus
      Epichloe festucae have contrasting roles for ROS production and symbiotic
      infection synchronized with the host plant.
AB  - Epichloe festucae is an endophytic fungus which systemically colonizes temperate
      grasses to establish symbiotic associations. Maintaining symptomless infection is
      a key requirement for endophytes, a feature that distinguishes them from
      pathogenic fungi. While pathogenic fungi extend their hyphae by tip growth,
      hyphae of E. festucae systemically colonize the intercellular space of expanding
      host leaves via a unique mechanism of hyphal intercalary growth. This study
      reports that two homologous Rho GTPases, Cdc42 and RacA, have distinctive roles
      in the regulation of E. festucae growth in planta. Here we highlight the vital
      role of Cdc42 for intercalary hyphal growth, as well as involvement of RacA in
      regulation of hyphal network formation, and demonstrate the consequences of
      mutations in these genes on plant tissue infection. Functions of Cdc42 and RacA
      are mediated via interactions with BemA and NoxR respectively, which are expected
      components of the ROS producing NOX complex. Symbiotic defects found in the racA
      mutant were rescued by introduction of a Cdc42 with key amino acids substitutions
      crucial for RacA function, highlighting the significance of the specific
      interactions of these GTPases with BemA and NoxR for their functional
      differentiation in symbiotic infection.

PMID- 29370296
TI  - Intracellular trafficking of begomoviruses in the midgut cells of their insect
      vector.
AB  - Begomoviruses are exclusively transmitted by whiteflies in a persistent
      circulative manner and cause considerable economic losses to crop production
      worldwide. Previous studies have shown that begomoviruses accumulate in vesicle
      like structures in whitefly midgut cells and that clathrin-mediated endocytosis
      is responsible for their internalization. However, the process by which
      begomoviruses are trafficked within whitefly midgut cells remains largely
      unknown. In this study, we investigated the roles of vesicle trafficking in the
      transport of Tomato yellow leaf curl virus (TYLCV), a begomovirus that has spread
      to over 50 countries and caused extensive damage to a range of important crops,
      within midgut cells of whitefly (Bemisia tabaci). By disrupting vesicle
      trafficking using RNA silencing and inhibitors, we demonstrated that the early
      steps of endosomal trafficking are important for the intracellular transport of
      TYLCV in the whitefly midgut. In addition, our data show that, unlike many animal
      viruses, TYCLV is trafficked within cells in a manner independent of recycling
      endosomes, late endosomes, lysosomes, the Golgi apparatus and the endoplasmic
      reticulum. Instead, our results suggest that TYLCV might be transported directly
      from early endosomes to the basal plasma membrane and released into the
      hemolymph. Silencing of the sorting nexin Snx12, which may be involved in
      membrane tubulation, resulted in fewer viral particles in hemolymph; this
      suggests that the tubular endosomal network may be involved in the transport of
      TYLCV. Our results also support a role for the endo-lysosomal system in viral
      degradation. We further showed that the functions of vector early endosomes and
      sorting nexin Snx12 are conserved in the transmission of several other
      begomoviruses. Overall, our data indicate the importance of early endosomes and
      the tubular endosomal network in begomovirus transmission.

PMID- 29370297
TI  - A novel PCR-based system for the detection of four species of human malaria
      parasites and Plasmodium knowlesi.
AB  - A microscopy-based diagnosis is the gold standard for the detection and
      identification of malaria parasites in a patient's blood. However, the detection
      of cases involving a low number of parasites and the differentiation of species
      sometimes requires a skilled microscopist. Although PCR-based diagnostic methods
      are already known to be very powerful tools, the time required to apply such
      methods is still much longer in comparison to traditional microscopic
      observation. Thus, improvements to PCR systems are sought to facilitate the more
      rapid and accurate detection of human malaria parasites Plasmodium falciparum, P.
      vivax, P. ovale, and P. malariae, as well as P. knowlesi, which is a simian
      malaria parasite that is currently widely distributed in Southeast Asia. A nested
      PCR that targets the small subunit ribosomal RNA genes of malaria parasites was
      performed using a "fast PCR enzyme". In the first PCR, universal primers for all
      parasite species were used. In the second PCR, inner-specific primers, which
      targeted sequences from P. falciparum, P. vivax, P. ovale, P. malariae, and P.
      knowlesi, were used. The PCR reaction time was reduced with the use of the "fast
      PCR enzyme", with only 65 minutes required to perform the first and second PCRs.
      The specific primers only reacted with the sequences of their targeted parasite
      species and never cross-reacted with sequences from other species under the
      defined PCR conditions. The diagnoses of 36 clinical samples that were obtained
      using this new PCR system were highly consistent with the microscopic diagnoses.

PMID- 29370298
TI  - Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a
      V2-directed broadly neutralizing antibody lineage.
AB  - Broadly neutralizing antibodies (bnAbs) to HIV-1 can evolve after years of an
      iterative process of virus escape and antibody adaptation that HIV-1 vaccine
      design seeks to mimic. To enable this, properties that render HIV-1 envelopes
      (Env) capable of eliciting bnAb responses need to be defined. Here, we followed
      the evolution of the V2 apex directed bnAb lineage VRC26 in the HIV-1 subtype C
      superinfected donor CAP256 to investigate the phenotypic changes of the virus
      populations circulating before and during the early phases of bnAb induction.
      Longitudinal viruses that evolved from the VRC26-resistant primary infecting (PI)
      virus, the VRC26-sensitive superinfecting (SU) virus and ensuing PI-SU
      recombinants revealed substantial phenotypic changes in Env, with a switch in Env
      properties coinciding with early resistance to VRC26. Decreased sensitivity of SU
      like viruses to VRC26 was linked with reduced infectivity, altered entry kinetics
      and lower sensitivity to neutralization after CD4 attachment. VRC26 maintained
      neutralization activity against cell-associated CAP256 virus, indicating that
      escape through the cell-cell transmission route is not a dominant escape pathway.
      Reduced fitness of the early escape variants and sustained sensitivity in cell
      cell transmission are both features that limit virus replication, thereby
      impeding rapid escape. This supports a scenario where VRC26 allowed only partial
      viral escape for a prolonged period, possibly increasing the time window for bnAb
      maturation. Collectively, our data highlight the phenotypic plasticity of the HIV
      1 Env in evading bnAb pressure and the need to consider phenotypic traits when
      selecting and designing Env immunogens. Combinations of Env variants with
      differential phenotypic patterns and bnAb sensitivity, as we describe here for
      CAP256, may maximize the potential for inducing bnAb responses by vaccination.

PMID- 29370299
TI  - Fungal diversity in oil palm leaves showing symptoms of Fatal Yellowing disease.
AB  - Oil palm (Elaeis guineensis Jacq.) is an excellent source of vegetable oil for
      biodiesel production; however, there are still some limitations for its
      cultivation in Brazil such as Fatal Yellowing (FY) disease. FY has been studied
      for many years, but its causal agent has never been determined. In Colombia and
      nearby countries, it was reported that the causal agent of Fatal Yellowing
      (Pudricion del Cogollo) is the oomycete Phytophthora palmivora, however, several
      authors claim that Fatal Yellowing and Pudricion del Cogollo (PC) are different
      diseases. The major aims of this work were to test, using molecular biology
      tools, Brazilian oil palm trees for the co-occurrence of the oomycete
      Phytophthora and FY symptoms, and to characterize the fungal diversity in FY
      diseased and healthy leaves by next generation sequencing. Investigation with
      specific primers for the genus Phytophthora showed amplification in only one of
      the samples. Analysis of the fungal ITS region demonstrated that, at the genus
      level, different groups predominated in all symptomatic samples, while
      Pyrenochaetopsis and unclassified fungi predominated in all asymptomatic samples.
      Our results show that fungal communities were not the same between samples at the
      same stage of the disease or among all the symptomatic samples. This is the first
      study that describes the evolution of the microbial community in the course of
      plant disease and also the first work to use high throughput next generation
      sequencing to evaluate the fungal community associated with leaves of oil palm
      trees with and without symptoms of FY.

PMID- 29370300
TI  - +mRNA expression of LRRC55 protein (leucine-rich repeat-containing protein 55) in
      the adult mouse brain.
AB  - LRRC55 (leucine-rich repeat-containing protein 55) protein is an auxiliary gamma
      subunit of BK (Big conductance potassium channel) channels, which leftward shifts
      GVs of BK channels around 50 mV in the absence of cytosolic Ca2+. LRRC55 protein
      is also the only gamma subunit of BK channels that is expressed in mammalian
      nervous system. However, the expression pattern of LRRC55 gene in adult mammalian
      brain remains elusive. In this study, we investigated the distribution of LRRC55
      mRNA in the adult mouse brain by using in situ hybridization. We found that
      LRRC55 mRNA is richly expressed in the adult mouse medial habenula nucleus (MHb),
      cerebellum and pons. However, the potential role of LRRC55 in MHb and cerebellum
      could be different based on the function of BK channels in these brain regions.

PMID- 29370302
TI  - Correction: Accounting for tourism benefits in marine reserve design.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0190187.].

PMID- 29370301
TI  - Widespread introgression of mountain hare genes into Fennoscandian brown hare
      populations.
AB  - In Fennoscandia, mountain hare (Lepus timidus) and brown hare (Lepus europaeus)
      hybridize and produce fertile offspring, resulting in gene flow across the
      species barrier. Analyses of maternally inherited mitochondrial DNA (mtDNA) show
      that introgression occur frequently, but unavailability of appropriate nuclear
      DNA markers has made it difficult to evaluate the scale- and significance for the
      species. The extent of introgression has become important as the brown hare is
      continuously expanding its range northward, at the apparent expense of the
      mountain hare, raising concerns about possible competition. We report here, based
      on analysis of 6833 SNP markers, that the introgression is highly asymmetrical in
      the direction of gene flow from mountain hare to brown hare, and that the levels
      of nuclear gene introgression are independent of mtDNA introgression. While it is
      possible that brown hares obtain locally adapted alleles from the resident
      mountain hares, the low levels of mountain hare alleles among allopatric brown
      hares suggest that hybridization is driven by stochastic processes. Interspecific
      geneflow with the brown hare is unlikely to have major impacts on mountain hare
      in Fennoscandia, but direct competition may.

PMID- 29370303
TI  - MERS-CoV 4b protein interferes with the NF-kappaB-dependent innate immune
      response during infection.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel human
      coronavirus that emerged in 2012, causing severe pneumonia and acute respiratory
      distress syndrome (ARDS), with a case fatality rate of ~36%. When expressed in
      isolation, CoV accessory proteins have been shown to interfere with innate
      antiviral signaling pathways. However, there is limited information on the
      specific contribution of MERS-CoV accessory protein 4b to the repression of the
      innate antiviral response in the context of infection. We found that MERS-CoV 4b
      was required to prevent a robust NF-kappaB dependent response during infection.
      In wild-type virus infected cells, 4b localized to the nucleus, while NF-kappaB
      was retained in the cytoplasm. In contrast, in the absence of 4b or in the
      presence of cytoplasmic 4b mutants lacking a nuclear localization signal (NLS),
      NF-kappaB was translocated to the nucleus leading to the expression of pro
      inflammatory cytokines. This indicates that NF-kappaB repression required the
      nuclear import of 4b mediated by a specific NLS. Interestingly, we also found
      that both in isolation and during infection, 4b interacted with alpha-karyopherin
      proteins in an NLS-dependent manner. In particular, 4b had a strong preference
      for binding karyopherin-alpha4 (KPNA4), which is known to translocate the NF
      kappaB protein complex into the nucleus. Binding of 4b to KPNA4 during infection
      inhibited its interaction with NF-kappaB-p65 subunit. Thereby we propose a model
      where 4b outcompetes NF-kappaB for KPNA4 binding and translocation into the
      nucleus as a mechanism of interference with the NF-kappaB-mediated innate immune
      response.

PMID- 29370304
TI  - The oral microbiome: A Lesson in coexistence.

PMID- 29370305
TI  - Alterations of HIV-1 envelope phenotype and antibody-mediated neutralization by
      signal peptide mutations.
AB  - HIV-1 envelope glycoprotein (Env) mediates virus attachment and entry into the
      host cells. Like other membrane-bound and secreted proteins, HIV-1 Env contains
      at its N terminus a signal peptide (SP) that directs the nascent Env to the
      endoplasmic reticulum (ER) where Env synthesis and post-translational
      modifications take place. SP is cleaved during Env biosynthesis but potentially
      influences the phenotypic traits of the Env protein. The Env SP sequences of HIV
      1 isolates display high sequence variability, and the significance of such
      variability is unclear. We postulate that changes in the Env SP influence Env
      transport through the ER-Golgi secretory pathway and Env folding and/or
      glycosylation that impact on Env incorporation into virions, receptor binding and
      antibody recognition. We first evaluated the consequences of mutating the charged
      residues in the Env SP in the context of infectious molecular clone HIV-1
      REJO.c/2864. Results show that three different mutations affecting histidine at
      position 12 affected Env incorporation into virions that correlated with
      reduction of virus infectivity and DC-SIGN-mediated virus capture and
      transmission. Mutations at positions 8, 12, and 15 also rendered the virus more
      resistant to neutralization by monoclonal antibodies against the Env V1V2 region.
      These mutations affected the oligosaccharide composition of N-glycans as shown by
      changes in Env reactivity with specific lectins and by mass spectrometry.
      Increased neutralization resistance and N-glycan composition changes were also
      observed when analogous mutations were introduced to another HIV-1 strain, JRFL.
      To the best of our knowledge, this is the first study showing that certain
      residues in the HIV-1 Env SP can affect virus neutralization sensitivity by
      modulating oligosaccharide moieties on the Env N-glycans. The HIV-1 Env SP
      sequences thus may be under selective pressure to balance virus infectiousness
      with virus resistance to the host antibody responses. (289 words).

PMID- 29370306
TI  - Impact of habitual physical activity and type of exercise on physical performance
      across ages in community-living people.
AB  - The maintenance of muscle function into late life protects against various
      negative health outcomes. The present study was undertaken to evaluate the impact
      of habitual physical activity and exercise types on physical performance across
      ages in community-living adults. The Longevity check-up 7+ (Lookup 7+) project is
      an ongoing cross-sectional survey conducted in unconventional settings (e.g.,
      exhibitions, malls, and health promotion campaigns across Italy) that began on
      June 1st 2015. The project was designed to raise awareness in the general
      population on major lifestyle behaviors and risk factors for chronic diseases.
      Candidate participants are eligible for enrolment if they are at least 18 years
      of age and provide written informed consent. Physical performance is evaluated
      through the 5-repetition chair stand test. Analyses were conducted in 6,242
      community-living adults enrolled between June 1st 2015 and June 30th 2017, after
      excluding 81 participants for missing values of the variables of interest. The
      mean age of the 6,242 participants was 54.4 years (standard deviation 15.2, range
      18-98 years), and 3552 (57%) were women. The time to complete the chair stand
      test was similar from 18 to 40-44 years, and declined progressively across
      subsequent age groups. Overall, the performance on the chair stand test was
      better in physically active participants, who completed the test with a mean of
      0.5 s less than sedentary enrollees (p < .001). After adjusting for potential
      confounders, a different distribution of physical performance across exercise
      intensities was observed, with better performance being recorded in participants
      engaged in more vigorous activities. Our findings suggest that regular physical
      activity modifies the age-related pattern of decline in physical performance,
      with greater benefits observed for more intensive activities. Efforts are needed
      from health authorities and healthcare providers to promote the large-scale
      adoption of an active lifestyle throughout the life course.

PMID- 29370307
TI  - The Wolbachia strain wAu provides highly efficient virus transmission blocking in
      Aedes aegypti.
AB  - Introduced transinfections of the inherited bacteria Wolbachia can inhibit
      transmission of viruses by Aedes mosquitoes, and in Ae. aegypti are now being
      deployed for dengue control in a number of countries. Only three Wolbachia
      strains from the large number that exist in nature have to date been introduced
      and characterized in this species. Here novel Ae. aegypti transinfections were
      generated using the wAlbA and wAu strains. In its native Ae. albopictus, wAlbA is
      maintained at lower density than the co-infecting wAlbB, but following transfer
      to Ae. aegypti the relative strain density was reversed, illustrating the strain
      specific nature of Wolbachia-host co-adaptation in determining density. The wAu
      strain also reached high densities in Ae. aegypti, and provided highly efficient
      transmission blocking of dengue and Zika viruses. Both wAu and wAlbA were less
      susceptible than wMel to density reduction/incomplete maternal transmission
      resulting from elevated larval rearing temperatures. Although wAu does not induce
      cytoplasmic incompatibility (CI), it was stably combined with a CI-inducing
      strain as a superinfection, and this would facilitate its spread into wild
      populations. Wolbachia wAu provides a very promising new option for arbovirus
      control, particularly for deployment in hot tropical climates.

PMID- 29370309
TI  - Correction: Dengue virus serotype 2 infection alters midgut and carcass gene
      expression in the Asian tiger mosquito, Aedes albopictus.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0171345.].

PMID- 29370308
TI  - Semaphorin3A induces nerve regeneration in the adult cornea-a switch from its
      repulsive role in development.
AB  - The peripheral sensory nerves that innervate the cornea can be easily damaged by
      trauma, surgery, infection or diabetes. Several growth factors and axon guidance
      molecules, such as Semaphorin3A (Sema3A) are upregulated upon cornea injury.
      Nerves can regenerate after injury but do not recover their original density and
      patterning. Sema3A is a well known axon guidance and growth cone repellent
      protein during development, however its role in adult cornea nerve regeneration
      remains undetermined. Here we investigated the neuro-regenerative potential of
      Sema3A on adult peripheral nervous system neurons such as those that innervate
      the cornea. First, we examined the gene expression profile of the Semaphorin
      class 3 family members and found that all are expressed in the cornea. However,
      upon cornea injury there is a fast increase in Sema3A expression. We then
      corroborated that Sema3A totally abolished the growth promoting effect of nerve
      growth factor (NGF) on embryonic neurons and observed signs of growth cone
      collapse and axonal retraction after 30 min of Sema3A addition. However, in adult
      isolated trigeminal ganglia or dorsal root ganglia neurons, Sema3A did not
      inhibited the NGF-induced neuronal growth. Furthermore, adult neurons treated
      with Sema3A alone produced similar neuronal growth to cells treated with NGF and
      the length of the neurites and branching was comparable between both treatments.
      These effects were replicated in vivo, where thy1-YFP neurofluorescent mice
      subjected to cornea epithelium debridement and receiving intrastromal pellet
      implantation containing Sema3A showed increased corneal nerve regeneration than
      those receiving pellets with vehicle. In adult PNS neurons, Sema3A is a potent
      inducer of neuronal growth in vitro and cornea nerve regeneration in vivo. Our
      data indicates a functional switch for the role of Sema3A in PNS neurons where
      the well-described repulsive role during development changes to a growth
      promoting effect during adulthood. The high expression of Sema3A in the normal
      and injured adult corneas could be related to its role as a growth factor.

PMID- 29370310
TI  - The reliability of molecular dynamics simulations of the multidrug transporter P
      glycoprotein in a membrane environment.
AB  - Despite decades of research, the mechanism of action of the ABC multidrug
      transporter P-glycoprotein (P-gp) remains elusive. Due to experimental
      limitations, many researchers have turned to molecular dynamics simulation
      studies in order to investigate different aspects of P-gp function. However, such
      studies are challenging and caution is required when interpreting the results. P
      gp is highly flexible and the time scale on which it can be simulated is limited.
      There is also uncertainty regarding the accuracy of the various crystal
      structures available, let alone the structure of the protein in a physiologically
      relevant environment. In this study, three alternative structural models of mouse
      P-gp (3G5U, 4KSB, 4M1M), all resolved to 3.8 A, were used to initiate sets of
      simulations of P-gp in a membrane environment in order to determine: a) the
      sensitivity of the results to differences in the starting configuration; and b)
      the extent to which converged results could be expected on the times scales
      commonly simulated for this system. The simulations suggest that the arrangement
      of the nucleotide binding domains (NBDs) observed in the crystal structures is
      not stable in a membrane environment. In all simulations, the NBDs rapidly
      associated (within 10 ns) and changes within the transmembrane helices were
      observed. The secondary structure within the transmembrane domain was best
      preserved in the 4M1M model under the simulation conditions used. However, the
      extent to which replicate simulations diverged on a 100 to 200 ns timescale meant
      that it was not possible to draw definitive conclusions as to which structure
      overall was most stable, or to obtain converged and reliable results for any of
      the properties examined. The work brings into question the reliability of
      conclusions made in regard to the nature of specific interactions inferred from
      previous simulation studies on this system involving similar sampling times. It
      also highlights the need to demonstrate the statistical significance of any
      results obtained in simulations of large flexible proteins, especially where the
      initial structure is uncertain.

PMID- 29370311
TI  - Correction: Evaluating the role of land cover and climate uncertainties in
      computing gross primary production in Hawaiian Island ecosystems.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0184466.].

PMID- 29370312
TI  - Correction: Widespread local chronic stressors in Caribbean coastal habitats.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0188564.].

PMID- 29370313
TI  - Correction: Fluctuations, Correlations and the Estimation of Concentrations
      inside Cells.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0151132.].

PMID- 29370314
TI  - Correction: Sexual assault incidents among college undergraduates: Prevalence and
      factors associated with risk.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186471.].

PMID- 29370316
TI  - The role of MGMT polymorphisms rs12917 and rs11016879 in head and neck cancer
      risk and prognosis.
AB  - Head and neck squamous cell carcinoma (HNSCC) is one of the leading cancers by
      incidence worldwide. The risk of these cancers is strictly associated with
      alkylation factors present in tobacco smoke. The crucial role in preventing DNA
      alkylation is played by O6-methylguanine-DNA methyltransferase (MGMT).
      Dysfunction or lack of MGMT is associated with an increased risk of cancer. The
      aim of the study was to assess the influence of MGMT polymorphisms: rs12917 and
      rs11016879 on HNSCC risk and course. The study consisted of 69 HNSCC patients and
      242 healthy individuals. Case samples were taken from resected tumour tissue. The
      control group comprised samples of epithelial cells collected from mucous
      membranes using swabs. DNA samples were genotyped by employing the 5' nuclease
      assay for allelic discrimination using TaqMan SNP Genotyping Assays. The
      significance between distributions of genotypes and alleles was tested using
      Pearson's chi2 test analysis. Our results indicated that the MGMT rs12917 TT
      genotype increases the risk of HNSCC. The MGMT rs11016879 AG genotype and A
      allele were associated with increased HNSCC risk. We noted higher risk of nodal
      metastasis in rs11016879 AA homozygotes. Mechanisms leading to MGMT enzymatic
      defect are unknown and hence further studies need to be carried out. Our data
      suggest that the examined polymorphisms may be considered as potential prognostic
      factors for HNSCC risk and outcome. Further studies are necessary to verify our
      results.

PMID- 29370315
TI  - Lipid droplet formation in Mycobacterium tuberculosis infected macrophages
      requires IFN-gamma/HIF-1alpha signaling and supports host defense.
AB  - Lipid droplet (LD) formation occurs during infection of macrophages with numerous
      intracellular pathogens, including Mycobacterium tuberculosis. It is believed
      that M. tuberculosis and other bacteria specifically provoke LD formation as a
      pathogenic strategy in order to create a depot of host lipids for use as a carbon
      source to fuel intracellular growth. Here we show that LD formation is not a
      bacterially driven process during M. tuberculosis infection, but rather occurs as
      a result of immune activation of macrophages as part of a host defense mechanism.
      We show that an IFN-gamma driven, HIF-1alpha dependent signaling pathway,
      previously implicated in host defense, redistributes macrophage lipids into LDs.
      Furthermore, we show that M. tuberculosis is able to acquire host lipids in the
      absence of LDs, but not in the presence of IFN-gamma induced LDs. This result
      uncouples macrophage LD formation from bacterial acquisition of host lipids. In
      addition, we show that IFN-gamma driven LD formation supports the production of
      host protective eicosanoids including PGE2 and LXB4. Finally, we demonstrate that
      HIF-1alpha and its target gene Hig2 are required for the majority of LD formation
      in the lungs of mice infected with M. tuberculosis, thus demonstrating that
      immune activation provides the primary stimulus for LD formation in vivo. Taken
      together our data demonstrate that macrophage LD formation is a host-driven
      component of the adaptive immune response to M. tuberculosis, and suggest that
      macrophage LDs are not an important source of nutrients for M. tuberculosis.

PMID- 29370317
TI  - The Maturing Antibiotic Mantra: "Shorter Is Still Better".

PMID- 29370319
TI  - Mortality, Length of Stay, and Cost of Weekend Admissions.
AB  - BACKGROUND: Apparent increase in mortality associated with being admitted to
      hospital on a weekend compared to weekdays has led to controversial policy
      changes to weekend staffing in the United Kingdom. Studies in the United States
      have been inconclusive and diagnosis specific, and whether to implement such
      changes is subject to ongoing debate. OBJECTIVE: To compare mortality, length of
      stay, and cost between patients admitted on weekdays and weekends. DESIGN:
      Retrospective cohort study. SETTING: National Inpatient Sample, an administrative
      claims database of a 20% stratified sample of discharges from all hospitals
      participating in the Healthcare Cost and Utilization Project. PATIENTS: Adult
      patients who were emergently admitted from 2012 to 2014. INTERVENTION: The
      primary predictor was whether the admission was on a weekday or weekend.
      MEASUREMENTS: The primary outcome was in-hospital mortality and secondary
      outcomes were length of stay and cost. RESULTS: We included 13,505,396 patients
      in our study. After adjusting for demographics and disease severity, we found a
      small difference in inpatient mortality rates on weekends versus weekdays (odds
      ratio [OR] 1.029; 95% confidence interval [CI], 1.020-1.039; P < .001). There was
      a statistically significant but clinically small decrease in length of stay
      (2.24%; 95% CI, 2.16-2.33; P < .001) and cost (1.14%; 95% CI, 1.05-1.24; P < 
      .001) of weekend admissions. A subgroup analysis of the most common weekend
      diagnoses showed substantial heterogeneity between diagnoses. CONCLUSIONS:
      Differences in mortality of weekend admissions may be attributed to underlying
      differences in patient characteristics and severity of illness and is subject to
      large between-diagnoses heterogeneity. Increasing weekend services may not result
      in desired reduction in inpatient mortality rate.

PMID- 29370318
TI  - Shorter Versus Longer Courses of Antibiotics for Infection in Hospitalized
      Patients: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Infection is a leading cause of hospitalization with high morbidity
      and mortality, but there are limited data to guide the duration of antibiotic
      therapy. PURPOSE: Systematic review to compare outcomes of shorter versus longer
      antibiotic courses among hospitalized adults and adolescents. DATA SOURCES:
      MEDLINE and Embase databases, 1990-2017. STUDY SELECTION: Inclusion criteria were
      human randomized controlled trials (RCTs) in English comparing a prespecified
      short course of antibiotics to a longer course for treatment of infection in
      hospitalized adults and adolescents aged 12 years and older. DATA EXTRACTION: Two
      authors independently extracted study characteristics, methods of statistical
      analysis, outcomes, and risk of bias. DATA SYNTHESIS: Of 5187 unique citations
      identified, 19 RCTs comprising 2867 patients met our inclusion criteria,
      including the following: 9 noninferiority trials, 1 superiority design trial, and
      9 pilot studies. Across 13 studies evaluating 1727 patients, no significant
      difference in clinical efficacy was observed (d = 1.6% [95% confidence interval
      (CI), -1.0%-4.2%]). No significant difference was detected in microbiologic cure
      (8 studies, d = 1.2% [95% CI, -4.1%-6.4%]), short-term mortality (8 studies, d =
      0.3% [95% CI, -1.2%-1.8%]), longer-term mortality (3 studies, d = -0.4% [95% CI, 
      6.3%-5.5%]), or recurrence (10 studies, d = 2.1% [95% CI, -1.2%-5.3%]).
      Heterogeneity across studies was not significant for any of the primary outcomes.
      CONCLUSIONS: Based on the available literature, shorter courses of antibiotics
      can be safely utilized in hospitalized patients with common infections, including
      pneumonia, urinary tract infection, and intra-abdominal infection, to achieve
      clinical and microbiologic resolution without adverse effects on mortality or
      recurrence.

PMID- 29370320
TI  - TXT2STAYQUIT: Pilot Randomized Trial of Brief Automated Smoking Cessation Texting
      Intervention for Inpatient Smokers Discharged from the Hospital.

PMID- 29370321
TI  - Reliability and Validity of the Diagnostic Criteria for Temporomandibular
      Disorders Axis I in Clinical and Research Settings: A Critical Appraisal.
AB  - The recently published Diagnostic Criteria for Temporomandibular Disorders
      (DC/TMD) Axis I, which is recommended for use in clinical and research settings,
      has provided an update of the Research Diagnostic Criteria for Temporomandibular
      Disorders (RDC/TMD). The authors of the DC/TMD based their publication on the
      results of a Validation Project (2001-2008) and consecutive workgroup sessions
      held between 2008 and 2013. The DC/TMD represents a major change in both content
      and procedures; nonetheless, earlier concerns and new insights have only partly
      been followed up when drafting the new recommendations. Moreover, the emphasis on
      immediate implementation in clinical and research settings is not in line with
      the provided external evidence on which the DC/TMD is based. This Focus Article
      describes these concerns with regard to several aspects of the DC/TMD: the
      additional classification categories; the high dependency on pressure-pain
      results from use of the recommended palpation technique; the TMD pain screening
      instrument; the test population characteristics; the utility of additional
      subgroups; the use of a reference standard; the dichotomy between pain and
      dysfunction; and the DC/TMD algorithms. Thus, although the DC/TMD represents an
      improvement over the RDC/TMD, its immediate implementation in research and
      clinical care does not yet appear to be adequately substantiated.

PMID- 29370323
TI  - Critical Commentary 2: Reliability and Validity of the DC/TMD Axis I.
AB  - No abstract available.

PMID- 29370322
TI  - Critical Commentary 1: Reliability and Validity of the DC/TMD Axis I.
AB  - No abstract available.

PMID- 29370324
TI  - Critical Commentary 3: Reliability and Validity of the DC/TMD Axis I.
AB  - No abstract available.

PMID- 29370325
TI  - Authors' Response to Critical Commentaries: Reliability and Validity of the
      DC/TMD Axis I.
AB  - No abstract available.

PMID- 29370330
TI  - Pan et al. Respond to "Secondhand Smoke and Cognitive Decline".

PMID- 29370331
TI  - The Great Recession and the Health of Young Children: A Fixed-Effects Analysis in
      Ireland.
AB  - Economic recessions have been linked to adult health, but few studies have
      examined how recessions influence the health of young children. This study
      examined the impact of life transitions linked to the recent financial crisis on
      the health of young children in Ireland. Data came from the Growing Up in Ireland
      Infant Cohort Study (n = 11,134), which assessed children before (2008), during
      (2011), and after (2013) the Great Recession that followed the financial crisis
      of 2008 and incorporated questions on the impacts of the financial crisis on
      families. Using fixed-effects models to control for confounding, we found that a
      reduction in welfare benefits during the recession was associated with a
      significant increase in the risks of asthma (beta = 0.014, 95% confidence
      interval (95% CI): 0.004, 0.023) and atopy (beta = 0.014, 95% CI: 0.001, 0.027).
      While parental job loss was not associated with child health, a reduction in
      working hours was associated with increased reports of child health problems
      (beta = 0.024, 95% CI: 0.004, 0.043), as were difficulties affording basic
      necessities (beta = 0.019, 95% CI: 0.001, 0.038). Results suggest that failing to
      protect vulnerable families and children during economic recessions may have long
      lasting implications for child health.

PMID- 29370332
TI  - Deployment and Preterm Birth Among US Army Soldiers.
AB  - With increasing integration of women into combat roles in the US military, it is
      critical to determine whether deployment, which entails unique stressors and
      exposures, is associated with adverse reproductive outcomes. Few studies have
      examined whether deployment increases the risk of preterm birth; no studies (to
      our knowledge) have examined a recent cohort of servicewomen. We therefore used
      linked medical and administrative data from the Stanford Military Data Repository
      for all US Army soldiers with deliveries between 2011 and 2014 to estimate the
      associations of prior deployment, recency of deployment, and posttraumatic stress
      disorder with spontaneous preterm birth (SPB), adjusting for sociodemographic,
      military-service, and health-related factors. Of 12,877 deliveries, 6.1% were
      SPBs. The prevalence was doubled (11.7%) among soldiers who delivered within 6
      months of their return from deployment. Multivariable discrete-time logistic
      regression models indicated that delivering within 6 months of return from
      deployment was strongly associated with SPB (adjusted odds ratio = 2.1, 95%
      confidence interval: 1.5, 2.9). Neither multiple past deployments nor
      posttraumatic stress disorder was significantly associated with SPB. Within this
      cohort, timing of pregnancy in relation to deployment was identified as a novel
      risk factor for SPB. Increased focus on servicewomen's pregnancy timing and
      predeployment access to reproductive counseling and effective contraception is
      warranted.

PMID- 29370334
TI  - Decisions and Incisions: The Role of Choice Architecture in Surgical Decision
      Making.

PMID- 29370335
TI  - Secondhand Smoke and Women's Cognitive Function in China.
AB  - Exposure to secondhand smoke (SHS) is known to be harmful to health. However, the
      association between household SHS and cognitive function among middle-aged and
      older women in China is understudied. Lagged dependent variable regression was
      used to examine the association between household SHS exposure and the cognitive
      function of married women who had been exposed to SHS, using data from 2 waves of
      the China Health and Retirement Longitudinal Study (CHARLS, 2011-2013).
      Controlling for age, educational attainment, geographic residence, household
      expenditures, and chronic conditions (i.e., hypertension, diabetes, and
      depressive symptoms), the results indicated that longer SHS exposure was
      associated with a greater decline in memory over 2 years. After comparing
      differences across age groups, this pattern was significant for women aged 55-64
      years. Furthermore, those who were illiterate, lived in rural areas, and reported
      depressive symptoms had a greater decline in memory. With evidence linking
      household SHS exposure with a higher risk of cognitive decline, effective
      education and public health intervention programs are urgently needed. Stronger
      tobacco control regulations and education about the dangers of household SHS are
      viable strategies to reduce the impending dementia epidemic in China.

PMID- 29370333
TI  - Orthostatic Hypotension and Symptoms in the AASK Trial.
AB  - BACKGROUND: Multiple definitions are used to characterize orthostatic hypotension
      (OH), but the degree to which these definitions correspond with orthostatic
      symptoms is unknown. METHODS: We analyzed data from African American Study of
      Kidney Disease and Hypertension (AASK), a randomized trial of African Americans
      with hypertension and kidney disease, to characterize the relationship between OH
      definitions and self-reported syncope, dizziness, or light-headedness.
      Orthostatic changes in systolic blood pressure (SBP), diastolic blood pressure
      (DBP), or heart rate (HR) were determined each visit after standing 2:45 minutes.
      OH was defined using the consensus definition (a drop in SBP >=20 mm Hg or DBP
      >=10 mm Hg) or an often used clinical substitute based on HR (an increase >=20
      bpm). RESULTS: Among 1,094 participants (mean age 54.5 +/- 10.7 years, 38.9%
      female), there were 52,636 visits (mean 48/person). Mean resting SBP, DBP, and HR
      at baseline were 147.7 +/- 22.3 mm Hg, 92.2 +/- 13.4 mm Hg, and 71.1 +/- 11.7
      bpm, respectively. While the OH consensus definition was associated with syncope
      (odds ratio 2.49; 95% confidence interval: 1.13, 5.51), dizziness (1.89; 1.53,
      2.33), and light-headedness (1.84; 1.52, 2.23), the clinical HR definition was
      only associated with dizziness (1.28; 1.07, 1.52). None of the OH components
      (SBP, DBP, or HR) reflected a natural threshold in the prevalence of symptoms;
      definitions using each of the 3 components were highly specific (>=96%) with low
      sensitivity (1-5%). CONCLUSIONS: While the consensus definition was more strongly
      associated with symptoms, OH definitions did not reflect natural thresholds in
      symptoms and were insensitive. This implies that the absence of OH using either
      consensus or clinical definitions does not exclude orthostatic symptoms, which
      has implications for evaluating clinical events like falls. CLINICAL TRIALS
      REGISTRATION: Trial Number: NCT01206062 (clinicaltrials.gov).

PMID- 29370336
TI  - Transplanting Patients with Alcohol-related Liver Disease in the National Health
      System: New Rules and Decisions.
AB  - Aims: The UK has a socialized healthcare system that provides treatment that is
      free at the point of care for acute and chronic health disorders (the National
      Health Service-NHS), which is currently experiencing a period of unprecedented
      challenge. Methods: A narrative review that discusses present and future
      arrangements for transplantation of alcohol-related liver disease (ArLD) in the
      UK. Results: Liver disease in the UK is reaching epidemic proportions due to
      obesity and metabolic disease compounding alcohol-mediated liver damage.
      Unfortunately, hepatology services in the UK are geographically disparate and
      subject to significant variations in liver morbidity and mortality, prompting
      concerns that this may negatively impair access to transplantation. In an attempt
      to improve referrals to tertiary liver services, the UK listing criteria for
      alcohol-associated liver disease were revised in 2016 by a working party under
      the aegis of the UK-Liver Advisory Group with the ambition of increasing
      opportunities for disease evaluation and improving the condition of candidates
      referred for assessment. Conclusion: Liver transplantation for ArLD is well
      established in the UK. Recent organizational changes seek to reduce inequities in
      access to transplant services. Short Summary: Liver disease in the UK is reaching
      epidemic proportions. Concerns over equity of access to liver transplantation
      prompted revision of the UK listing criteria for alcohol-associated liver disease
      in 2016, to improve to the availability of tertiary hepatology services.
      Transplanting patients with alcohol-related liver disease in the National Health
      System: New Rules and Decisions '...The second property of your excellent sherris
      is, the warming of the blood; which, before cold and settled, hath left the liver
      white and pale...'Falstaff; Henry IV Part 2: Act 4, Scene 3.

PMID- 29370337
TI  - A functional-structural model of ephemeral seagrass growth influenced by
      environment.
AB  - Background and Aims: Ephemeral seagrasses that respond rapidly to environmental
      changes are important marine habitats. However, they are under threat due to
      human activity and are logistically difficult and expensive to study. This study
      aimed to develop a new functional-structural environmentally dependent model of
      ephemeral seagrass, able to integrate our understanding of ephemeral seagrass
      growth dynamics and assess options for potential management interventions, such
      as seagrass transplantation. Methods: A functional-structural plant model was
      developed in which growth and senescence rates are mechanistically linked to
      environmental variables. The model was parameterized and validated for a
      population of Halophila stipulacea in the Persian Gulf. Key Results: There was a
      good match between empirical and simulated results for the number of apices, net
      rhizome length or net number of internodes using a 330 d simulation. Simulated
      data were more variable than empirical data. Simulated structural patterns of
      seagrass rhizome growth qualitatively matched empirical observations.
      Conclusions: This new model successfully simulates the environmentally dependent
      growth and senescence rates of our case-study ephemeral seagrass species. It
      produces numerical and visual outputs that help synthesize our understanding of
      how the influence of environmental variables on plant functional processes
      affects overall growth patterns. The model can also be used to assess the
      potential outcomes of management interventions like seagrass transplantation,
      thus providing a useful management tool. It is freely available and easily
      adapted for new species and locations, although validation with more species and
      environments is required.

PMID- 29370338
TI  - RE: "DIETARY INTAKE OF ANTIOXIDANT VITAMINS AND CAROTENOIDS AND RISK OF
      DEVELOPING ACTIVE TUBERCULOSIS IN A PROSPECTIVE POPULATION-BASED COHORT".

PMID- 29370339
TI  - Projections of multi-morbidity in the older population in England to 2035:
      estimates from the Population Ageing and Care Simulation (PACSim) model.
AB  - Background: models projecting future disease burden have focussed on one or two
      diseases. Little is known on how risk factors of younger cohorts will play out in
      the future burden of multi-morbidity (two or more concurrent long-term
      conditions). Design: a dynamic microsimulation model, the Population Ageing and
      Care Simulation (PACSim) model, simulates the characteristics (sociodemographic
      factors, health behaviours, chronic diseases and geriatric conditions) of
      individuals over the period 2014-2040. Population: about 303,589 individuals aged
      35 years and over (a 1% random sample of the 2014 England population) created
      from Understanding Society, the English Longitudinal Study of Ageing, and the
      Cognitive Function and Ageing Study II. Main outcome measures: the prevalence of,
      numbers with, and years lived with, chronic diseases, geriatric conditions and
      multi-morbidity. Results: between 2015 and 2035, multi-morbidity prevalence is
      estimated to increase, the proportion with 4+ diseases almost doubling
      (2015:9.8%; 2035:17.0%) and two-thirds of those with 4+ diseases will have mental
      ill-health (dementia, depression, cognitive impairment no dementia). Multi
      morbidity prevalence in incoming cohorts aged 65-74 years will rise (2015:45.7%;
      2035:52.8%). Life expectancy gains (men 3.6 years, women: 2.9 years) will be
      spent mostly with 4+ diseases (men: 2.4 years, 65.9%; women: 2.5 years, 85.2%),
      resulting from increased prevalence of rather than longer survival with multi
      morbidity. Conclusions: our findings indicate that over the next 20 years there
      will be an expansion of morbidity, particularly complex multi-morbidity (4+
      diseases). We advocate for a new focus on prevention of, and appropriate and
      efficient service provision for those with, complex multi-morbidity.

PMID- 29370340
TI  - Living Donor Liver Transplantation for Alcoholic Liver Disease.
AB  - Aims: Alcoholic liver disease (ALD) is now a well-recognized indication for liver
      transplantation. This paper reviews existing literature on living donor liver
      transplantation (LDLT) for ALD and presents data from a single, high volume
      United States liver transplant center. Methods: For the literature review, a
      PubMed search was undertaken using the search terms 'living donor' and 'alcoholic
      liver disease'. Studies were included that presented outcome data for patients
      who underwent LDLT for ALD. For the single-center data collection, all patients
      who underwent LDLT from 2003 to 2016 at our center were reviewed and the data for
      recipients with ALD was subsequently analyzed and compared with those patients
      who underwent LDLT for other indications. Results: Of 110 studies that resulted
      from the PubMed query, only 5 contained data that was relevant to this
      manuscript. These studies represented data collected from two Asian countries:
      one single center in Korea and a collection of centers in Japan. The relapse rate
      following LDLT for ALD ranged from 7.9% to 22%, and pre-transplant abstinence did
      not impact post-transplant relapse in any of these studies. For the single-center
      data, of 136 LDLT performed at our institution during the time period, 22 were
      performed for ALD. There was no difference in 1- or 5-year survival between
      patients transplanted for ALD and those transplanted for other etiologies (94.7%
      vs. 93.4%, P = 0.79 and 78.9% vs. 87.5%, P = 0.6). Conclusion: There is a very
      limited amount of data available on LDLT for ALD. Existing data suggests that
      LDLT for ALD results in excellent outcomes. Short Summary: Published data on
      living donor liver transplantation (LDLT) for alcoholic liver disease (ALD) are
      limited. One- and five-year survival rates range from 82% to 100% and 78% to 87%,
      respectively. Rates of alcohol relapse following transplant appear low, ranging
      from 7% to 23%; 6-month abstinence periods prior to LDLT for ALD do not appear to
      have a significant impact on relapse.

PMID- 29370341
TI  - Infection Control and What to Wear in the Operating Room.

PMID- 29370342
TI  - Invited Commentary: Secondhand Smoke-an Underrecognized Risk Factor for Cognitive
      Decline.
AB  - Pan et al. (Am J Epidemiol. 2018;187(5):911-918) reported findings that exposure
      to secondhand smoke (SHS) was associated with cognitive decline over the course
      of 2 years among middle-aged and older Chinese women who never smoked, and they
      also reported a dose-response relationship. SHS exposure affects vulnerable
      people disproportionately because they have less control or choice over their
      living and working environment. Smoking is an established risk factor for
      dementia, but recent evidence reports on dementia-risk increase have not included
      SHS. Many epidemiologic studies collect data on smoking but not SHS exposure. SHS
      may be one of the most prevalent and modifiable risk factors for cognitive
      decline and therefore represents a major potential target for reduction of
      dementia risk. Given the high prevalence of smoking in China and other parts of
      the world, there is an urgent need to raise awareness of SHS reduction as part of
      global and national strategies to reduce cognitive decline and dementia and to
      introduce legislation that protects nonsmokers and vulnerable children and adults
      from SHS.

PMID- 29370343
TI  - Reply to Hambraeus and Lytsy.

PMID- 29370344
TI  - Carcinogenic response and other histopathological alterations in mice exposed to
      cigarette smoke for varying time periods after birth.
AB  - In spite of the outstanding role of tobacco smoking in human carcinogenesis, it
      is difficult to reproduce its effects in experimental animals. Based on the
      knowledge that a variety of mechanisms account for a higher susceptibility to
      carcinogens early in life, we have developed a murine model in which mainstream
      cigarette smoke becomes convincingly carcinogenic. The standard model involves
      exposure to smoke for 4 months, starting after birth, followed by an additional 3
      4 months in filtered air. We evaluated herein the time- and dose-dependent
      response, at 7.5 months of life, of Swiss H mice that had been exposed to smoke
      for either 1, 2 or 4 months after birth. A one-month exposure, corresponding to a
      period of intense alveolarization, was sufficient to induce most inflammatory,
      degenerative and preneoplastic pulmonary lesions, including emphysema and
      alveolar epithelial hyperplasia, blood vessel proliferation and hemangiomas,
      reflecting an early proangiogenic role of smoking, and microadenomas bearing ki
      67-positive proliferating cells as well as urinary bladder epithelial
      hyperplasia. Two months of exposure were needed to induce pulmonary adenomas and
      urinary bladder papillomas in males only, which highlights a protective role of
      estrogens in urinary bladder carcinogenesis. Four months, which in humans would
      correspond to the postnatal period, puberty, adolescence and early adulthood,
      were needed to induce other lesions, including tubular epithelial hyperplasia of
      kidney, bronchial epithelial hyperplasia and especially pulmonary malignant
      tumors. These findings highlight the concept that preneoplastic and neoplastic
      lesions occurring in adulthood can be induced by exposure to smoke early in life.

PMID- 29370347
TI  - Artemisinin Therapy for Malaria in Hemoglobinopathies: A Systematic Review.
AB  - Artemisinin derivatives are widely used antimalarial drugs. There is some
      evidence from in vitro, animal and clinical studies that hemoglobinopathies may
      alter their disposition and antimalarial activity. This review assesses relevant
      data in alpha-thalassemia, sickle cell disease (SCD), beta-thalassemia and
      hemoglobin E. There is no convincing evidence that the disposition of artemisinin
      drugs is affected by hemoglobinopathies. Although in vitro studies indicate that
      Plasmodium falciparum cultured in thalassemic erythrocytes is relatively
      resistant to the artemisinin derivatives, mean 50% inhibitory concentrations
      (IC50s) are much lower than in vivo plasma concentrations after recommended
      treatment doses. Since IC50s are not increased in P. falciparum cultures using
      SCD erythrocytes, delayed post-treatment parasite clearance in SCD may reflect
      hyposplenism. As there have been no clinical studies suggesting that
      hemoglobinopathies significantly attenuate the efficacy of artemisinin
      combination therapy (ACT) in uncomplicated malaria, recommended artemisinin doses
      as part of ACT remain appropriate in this patient group.

PMID- 29370345
TI  - Sucrose supply from leaves is required for aerenchymatous phellem formation in
      hypocotyl of soybean under waterlogged conditions.
AB  - Background and Aims: Soil waterlogging often causes oxygen deficiency in the root
      systems of plants and severely inhibits plant growth. Formation of aerenchyma -
      interconnected spaces that facilitate the movement of gases between and within
      the aerial and submerged parts of plants - is an adaptive trait for coping with
      waterlogged conditions. Soybean (Glycine max) forms porous secondary tissues
      known as aerenchymatous phellem (AP), which are derived from the outermost cell
      layer of phellogen. To understand what factors other than waterlogging are
      involved in phellogen and AP formation, we examined how their formation in
      soybean seedlings was affected by darkness, CO2 deficiency and blockage of phloem
      transport. Methods: Aerenchymatous phellem and phellogen formation were expressed
      as area ratios in cross-sections of hypocotyl. CO2 was depleted by use of calcium
      oxide and sodium hydroxide. Phloem transport was blocked by heat-girdling of
      hypocotyls. Sucrose levels were measured by spectrophotometry. Key Results: Under
      light conditions, waterlogging induced the accumulation of high concentrations of
      sucrose in hypocotyls, followed by phellogen and AP formation in hypocotyls.
      Phellogen formation and AP formation were inhibited by darkness, CO2 deficiency
      and blockage of phloem transport. Phellogen formation and AP formation were also
      inhibited by excision of shoots above the epicotyl, but they recovered following
      application of sucrose (but not glucose or fructose application) to the cut
      surface. Conclusions: The results demonstrate that sucrose derived from leaves is
      essential for AP and phellogen formation in soybean hypocotyls under waterlogged
      soil conditions. Maintenance of a high sucrose concentration is thus essential
      for the development of phellogen and AP and the differentiation of phellogen to
      AP.

PMID- 29370346
TI  - Reduced Risk of Inflammatory Bowel Disease-associated Colorectal Neoplasia with
      Use of Thiopurines: a Systematic Review and Meta-analysis.
AB  - Background and Aims: The association between thiopurines and colorectal neoplasia
      risk remains controversial in inflammatory bowel disease [IBD] patients. We
      performed a systematic review and meta-analysis examining this association.
      Methods: A comprehensive search of the PubMed, EMBASE and Cochrane Library
      databases was performed to identify relevant literature. Random-effects models
      were applied to calculate the pooled odds ratio [OR] and relative risk [RR] with
      corresponding 95% confidence intervals [CIs] among case-control and cohort
      studies. Results: Eleven cohort and 16 case-control studies involving 95397
      patients were included in this study. Overall, the use of thiopurines was
      associated with a reduced risk of colorectal neoplasia both in case-control [OR =
      0.49, 95% CI: 0.34-0.70] and cohort studies [RR = 0.96, 95% CI: 0.94-0.98].
      Moreover, a protective effect of thiopurines against advanced neoplasia [high
      grade dysplasia and cancer] [OR = 0.51, 95% CI: 0.31-0.84 for case-control
      studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] and colorectal cancer
      [CRC] [OR = 0.56, 95% CI: 0.34-0.93 for case-control studies; RR = 0.96, 95% CI:
      0.94-0.98 for cohort studies] was also observed. Furthermore, when the analysis
      was conducted on patients at a high risk for colorectal neoplasia, the
      chemopreventive effect was confirmed in patients with long disease duration [> 8
      years] but not in those with extensive colitis or primary sclerosing cholangitis.
      Conclusions: This study demonstrated that thiopurine use was associated with a
      reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients,
      especially those with long disease duration [> 8 years].

PMID- 29370349
TI  - Left atrial appendage resection can be performed minimally invasively with good
      clinical and echocardiographic outcomes without any severe risk.
AB  - OBJECTIVES: The adverse effects of left atrial appendage (LAA) closure have not
      yet been evaluated. This study aimed to prove the safety and low invasiveness of
      LAA resection through our thoracoscopic stand-alone left atrial appendectomy
      experience. METHODS: Eighty-seven patients [mean age 68 +/- 9 years, 68 men
      (78%), mean congestive heart failure, hypertension, age >= 75 years, diabetes
      mellitus, prior stroke or transient ischaemic attack to thromboembolism, vascular
      disease, age 65-74 years and sex category (CHA2DS2-VASc) score 2.9 +/- 1.6
      points] who had undergone thoracoscopic left atrial appendectomy were selected.
      The operative and clinical data (left atrial diameter, left ventricular diameter
      of systole/diastole, ejection fraction, brain natriuretic peptide and human
      atrial natriuretic peptide) were evaluated. All procedures were performed without
      cardiopulmonary bypass or cardiac arrest. The LAA was resected with an endoscopic
      linear cutter device. Except for 1 case with severe pleural adhesion, all
      operations were performed thoracoscopically. RESULTS: The preoperative and
      postoperative data are as follows: left atrial diameter 43 +/- 5 mm and 43 +/- 5
      mm (P = 0.8); left ventricular diameter of systole/diastole 50 +/- 5/35 +/- 6 mm
      and 48 +/- 5/34 +/- 6 mm (P < 0.01); ejection fraction 57 +/- 10% and 56 +/- 10%
      (P = 0.11); brain natriuretic peptide 97 +/- 77 pg/ml and 72 +/- 65 pg/ml (P <
      0.01) and human atrial natriuretic peptide 73 +/- 64 pg/ml and 96 +/- 67 pg/ml (P
      = 0.03), respectively. The mean volume of bleeding in the operation was very
      small (<10 ml). The mean length of postoperative in-hospital stay was 3.8 +/- 1.8
      days. All the patients were discharged while maintaining their preoperative
      activities of daily living without major complications. No thrombus or residual
      stumps were detected during the 3-month postoperative computed tomography follow
      up. The perioperative heart function did not change significantly in this study.
      Bleeding with resection was minimal, and no rebleeding events occurred.
      CONCLUSIONS: LAA resection did not affect negatively on the cardiac function and
      did not increase the risk of bleeding risk.

PMID- 29370348
TI  - Clostridium difficile Whole Genome Sequencing Reveals Limited Transmission Among
      Symptomatic Children: A Single-Center Analysis.
AB  - Background: Although pediatric Clostridium difficile infections (CDIs) are
      increasing, C. difficile transmission patterns among children are poorly
      understood. Methods: We performed whole genome sequencing (WGS) on C. difficile
      isolates collected from children diagnosed with CDI between December 2012 and
      December 2013 at a single academic medical center. Genome sequences of isolates
      from CDIs diagnosed >=8 weeks after study initiation were compared to all study
      isolate genome sequences. Among patients with isogenic isolates (<=2-3 core
      genome single nucleotide variants [SNVs] identified by pairwise SNV analyses),
      common inpatient and/or outpatient healthcare exposures were investigated.
      Results: Among 131 CDIs in 107 children, WGS identified 104 genetically distinct
      isolates. Of 84 incident CDIs occurring >=8 weeks after study initiation, only 10
      (11.9%) were caused by a strain isogenic to another cohort CDI isolate (putative
      transmission events). Proportions of each CDI class putatively associated with
      transmission were hospital-onset healthcare facility-associated (HCFA), 2/16
      (12.5%); community-onset HCFA, 1/17 (5.9%); indeterminate, 1/11 (9.1%); community
      associated (CA), 5/40 (12.5%); and recurrent, 1/21 (4.8%). Transmission events
      among CA and HCFA CDIs were similarly infrequent (5/40 [12.5%] vs 3/33 [9.1%]; P
      = .64). Shared healthcare facility exposures were only identified among 7/10
      putative transmission events. Potential community transmission (same postal code)
      was not identified. Conclusions: WGS identified a highly diverse group of C.
      difficile isolates among children with CDI, including those with HCFA CDI.
      Clostridium difficile transmission among symptomatic children was very uncommon.
      Among putatively transmitted cases, investigation of shared healthcare exposures
      often did not identify a potential transmission source.

PMID- 29370350
TI  - Long-term Use of Tedizolid as Suppressive Therapy for Recurrent Methicillin
      Resistant Staphylococcus aureus Graft Infection.

PMID- 29370352
TI  - A Multicenter, Prospective, Randomized, Contralateral Study of Tissue
      Liquefaction Liposuction vs Suction-Assisted Liposuction.
AB  - Background: Tissue liquefaction liposuction (TLL) deploys a novel energy source
      utilizing a stream of warmed, low-pressurized, and pulsed saline to extract fat
      tissue. Objectives: Compare TLL to suction-assisted liposuction (SAL) to
      determine which device is more efficient for surgeons and provides better
      recovery for patients. Methods: Thirty-one adult female patients were followed
      prospectively in a contralateral study design comparing differences in bruising,
      swelling, tenderness, and incision appearance ratings between TLL and SAL
      procedures. Surgical efficiency and appearance of the lipoaspirate were also
      compared. Results: All 31 patients successfully completed the study. For TLL and
      SAL procedures, the average volumes of infusion (1.242 vs 1.276 L) and aspirated
      supernatant fat (704 vs 649 mL) were statistically similar. TLL median fat
      extraction rate was faster than SAL (35.6 vs 25 mL/min; P < 0.0001), and stroke
      rate was reduced in TLL vs SAL procedures (48 vs 120 strokes/min; P < 0.0001),
      and both were statistically significant. The mean total scores for bruising,
      swelling, treatment site tenderness, and incision appearance were lower,
      indicating improved patient recovery on the TLL side. Conclusions: TLL and SAL
      techniques produced comparable volume of fat aspirate. TLL demonstrated a 42%
      faster fat extraction rate and a 68% reduction in arm movements needed to
      complete the procedure compared to SAL, both of these differences are
      statistically significant. The TLL side was noted to have reduced bruising and
      swelling and improved incision site appearance with less tenderness compared to
      the SAL side. Level of Evidence 2: 

PMID- 29370353
TI  - Erratum.

PMID- 29370351
TI  - Combined Hyperglycemia- and Hyperinsulinemia-Induced Insulin Resistance in
      Adipocytes Is Associated With Dual Signaling Defects Mediated by PKC-zeta.
AB  - A hyperglycemic and hyperinsulinemic environment characteristic of type 2
      diabetes causes insulin resistance. In adipocytes, defects in both insulin
      sensitivity and maximum response of glucose transport have been demonstrated. To
      investigate the molecular mechanisms, freshly isolated rat adipocytes were
      incubated in control (5.6 mM glucose, no insulin) and high glucose (20 mM)/high
      insulin (100 nM) (HG/HI) for 18 hours to induce insulin resistance. Insulin
      resistant adipocytes manifested decreased sensitivity of glucose uptake
      associated with defects in insulin receptor substrate (IRS)-1 Tyr
      phosphorylation, association of p85 subunit of phosphatidylinositol-3-kinase, Akt
      Ser473 and Thr308 phosphorylation, accompanied by impaired glucose transporter 4
      translocation. In contrast, protein kinase C (PKC)-zeta activity was augmented by
      chronic HG/HI. Inhibition of PKC-zeta with a specific cell-permeable peptide
      reversed the signaling defects and insulin sensitivity of glucose uptake.
      Transfection of dominant-negative, kinase-inactive PKC-zeta blocked insulin
      resistance, whereas constitutively active PKC-zeta recapitulated the defects. The
      HG/HI incubation was associated with stimulation of IRS-1 Ser318 and Akt Thr34
      phosphorylation, targets of PKC-zeta. Transfection of IRS-1 S318A and Akt T34A
      each partially corrected insulin signaling, whereas combined transfection of both
      completely normalized insulin signaling. In vivo hyperglycemia/hyperinsulinemia
      in rats for 48 hours similarly resulted in activation of PKC-zeta and increased
      phosphorylation of IRS-1 Ser318 and Akt Thr34. These data indicate that
      impairment of insulin signaling by chronic HG/HI is mediated by dual defects at
      IRS-1 and Akt mediated by PKC-zeta.

PMID- 29370354
TI  - Systematic evaluation of collateral pathways to the artery of Adamkiewicz using
      computed tomography.
AB  - OBJECTIVES: Preoperative identification of the artery of Adamkiewicz can help
      prevent postoperative spinal cord injury in patients undergoing thoracic and
      thoraco-abdominal aortic aneurysm repair. Although several studies have shown the
      feasibility of evaluating the artery of Adamkiewicz using multidetector row
      computed tomography (MDCT), no detailed investigations regarding the collateral
      circulation to the artery of Adamkiewicz have been performed. The purpose of this
      study was to investigate the collateral circulation to the artery of Adamkiewicz
      using MDCT in patients with thoracic and thoraco-abdominal aortic aneurysms.
      METHODS: Our institutional review board approved this study. Sixty-four patients
      with descending thoracic and thoraco-abdominal aortic aneurysms associated with
      the occlusion of the segmental artery from which the artery of Adamkiewicz
      originated were scanned using 64- or 320-detector row computed tomography. Two
      independent observers evaluated the MDCT images based on the degree of
      visualization of the artery of Adamkiewicz and its collateral circulation using a
      4-point scale. RESULTS: The average visualization score was 2.8 +/- 0.6. In 53 of
      the 64 (83%) patients, image quality was judged to be diagnostic. MDCT
      demonstrated 75 collateral pathways to the artery of Adamkiewicz in these 53
      patients. Sixty-four of the 75 (85%) pathways were collaterals around the spinal
      column, and the remaining 11 (15%) pathways were collateral arteries in the
      thoracic wall. CONCLUSIONS: MDCT revealed the collateral pathways to the artery
      of Adamkiewicz around the spinal column and in the thoracic wall in 83% of our
      patients with thoracic and thoraco-abdominal aortic aneurysms.

PMID- 29370355
TI  - Commentary on: Vaginal Laxity, Sexual Distress, and Sexual Dysfunction: A Cross
      Sectional Study in a Plastic Surgery Practice.

PMID- 29370357
TI  - Ultra fast-track minimally invasive aortic valve replacement: going beyond
      reduced incisions.
AB  - Aortic valve replacement (AVR) via a median sternotomy approach has been largely
      reported to be safe and long-term efficacious, and currently represents the 'gold
      standard' approach for aortic stenosis treatment. However, aortic valve surgery
      has undergone continuous development over the last years, involving less invasive
      techniques and new technologies to reduce the traumatic impact of the
      intervention and extend the operability toward increasingly high-risk patients.
      Indeed, minimally invasive AVR and transcatheter aortic valve replacement
      caseload have steadily increased leading to a paradigm shift in the treatment of
      aortic valve disease. In this setting, we have established a multidisciplinary
      minimally invasive programme to treat patients who require AVR. Herein, we
      present our approach including (i) reduced chest incision (through a J
      ministernotomy), aiming to reduce the traumatic impact of the surgical procedure,
      to decrease blood loss, postoperative pain and wound complications and to
      increase patient's satisfaction; (ii) rapid-deployment AVR, to reduce operative
      times, to facilitate minimally invasive approach and to improve haemodynamic
      outcomes; (iii) minimal invasive extracorporeal circulation system, to improve
      end-organ protection, to decrease systemic inflammatory response and to promote
      fast-track anaesthesia and (iv) ultra fast-track anaesthesia, to decrease the
      rate of postoperative complications and assure better and earlier recovery.

PMID- 29370356
TI  - Moving Forward With Treatment of Gonorrhea for Users of Human Immunodeficiency
      Virus Preexposure Prophylaxis Given the Threat of Antimicrobial Resistance.

PMID- 29370358
TI  - Vaginal Laxity, Sexual Distress, and Sexual Dysfunction: A Cross-Sectional Study
      in a Plastic Surgery Practice.
AB  - Background: Sexual health issues can be characterized by vaginal laxity (VL),
      sexual distress, and sexual dysfunction. The epidemiology of these issues in
      plastic surgery patients, and especially breast cancer survivors, remains poorly
      understood. Objectives: To prospectively assess sexual health issues in a plastic
      surgery patient population with and without breast cancer. Methods: A prospective
      cohort study was created in our practice from June to August 2017 with
      administration of a survey including the vaginal laxity questionnaire (VLQ),
      female sexual distress scale-revised (FSDS-R), and female sexual function index
      (FSFI). Multivariate logistic regression identified the controlled effect of
      patient variables on development of sexual health issues. Results: Of 291
      patients solicited, 239 completed the survey (37.7% breast cancer survivors vs
      62.3% without). Prevalence of VL was nearly 1 in 6 women. Of these, 46.0% met
      criteria for sexual distress (FSDS-R >= 11.0) and 64.8% had sexual dysfunction
      (FSFI <= 26.5). Breast cancer survivors exhibited significantly greater overall
      sexual dysfunction (P < 0.001) and greater dysfunction within all FSFI domains of
      desire, arousal, lubrication, orgasm, satisfaction, and pain (all P < 0.02). On
      multivariate regression, number of vaginal deliveries predicted development of VL
      (OR 1.87, P < 0.001), presence of VL predicted sexual distress (OR 3.01, P =
      0.007), while history of breast cancer predicted sexual dysfunction (OR 1.87, P <
      0.05). Conclusions: Sexual health issues are prevalent amongst plastic surgery
      patients. Aesthetic practices can improve patients' quality of life by focusing
      on these areas. Potential therapeutic options to address sexual health issues
      should consider addressing vaginal laxity. Level of Evidence 2: 

PMID- 29370360
TI  - Reply to Dinh et al.

PMID- 29370361
TI  - Hyperhomocysteinemia and Risk of First Venous Thrombosis: The Influence of
      (Unmeasured) Confounding Factors.
AB  - Meta-analyses have reported a 2- to 3-fold increased risk of venous thrombosis
      (VT) in individuals with hyperhomocysteinemia. However, confounding factors were
      generally not considered. In contrast, randomized trials of homocysteine-lowering
      therapy and VT risk have been negative. We investigated whether
      hyperhomocysteinemia was associated with VT in the Multiple Environmental and
      Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) case-control
      study (1999-2004) from the Netherlands (1,689 cases and 1,726 controls), taking
      into account measured and unmeasured confounders. We compared patients with
      population controls to estimate odds ratios using unconditional logistic
      regression and adjusted for various potential confounders. We matched patients to
      their partners to additionally adjust for unmeasured confounders (e.g., lifestyle
      factors) using conditional logistic regression. We found that elevated
      homocysteine concentrations were not associated with an increased risk for VT
      when comparing patients with population controls, either as a continuous variable
      (odds ratio = 1.00, 95% confidence interval: 0.99, 1.01), in terms of 0.7-mg/L
      increase (odds ratio = 0.99, 95% confidence interval: 0.93, 1.05), or within
      different homocysteine categories. We obtained similar results when patients were
      compared with their partners. Stratification by sex, deep vein thrombosis,
      pulmonary embolism, provoked VT, and unprovoked VT also provided no evidence of
      an association. In conclusion, after extensive adjustments for confounding,
      hyperhomocysteinemia was not associated with an increased risk of venous
      thrombosis in this study.

PMID- 29370359
TI  - Smoking is Associated with an Increased Risk of Microscopic Colitis: Results From
      Two Large Prospective Cohort Studies of US Women.
AB  - Background: Long-term data on the influence of smoking on risk of microscopic
      colitis are limited. We therefore sought to examine and characterize the
      association between smoking and risk of incident microscopic colitis in two large
      prospective cohorts of women. Methods: We conducted a prospective study of 231015
      women enrolled in the Nurses' Health Study [NHS] and NHSII. Information regarding
      smoking, other lifestyle factors and medications were collected biennially from
      1976 to 2012 in NHS and from 1989 to 2013 in NHSII. Incident cases of microscopic
      colitis were confirmed through physician medical record review. We used Cox
      proportional hazards modelling to examine the association between smoking and
      risk of microscopic colitis. Results: We documented 166 incident cases of
      microscopic colitis over 6122779 person-years of follow up. Compared to non
      smokers, the multivariable-adjusted hazard ratio [HR] for microscopic colitis was
      2.52 (95% confidence interval [CI] 1.59-4.00) amongst current smokers and 1.54
      [95% CI 1.09-2.17] amongst past smokers. The risk increased with higher pack
      years of smoking [p trend = 0.001] and diminished following smoking cessation [p
      trend = 0.017]. Current smoking appeared to be more strongly associated with risk
      of collagenous colitis [HR 3.68; 95% CI 1.94-6.97] than lymphocytic colitis [HR
      1.71; 95% CI 0.83-3.53]. Conclusion: In two large prospective cohort studies, we
      observed an association between current smoking and risk of microscopic colitis.
      Risk of microscopic colitis appeared to increase with higher pack-years and
      diminish following smoking cessation. Future studies focused on characterizing
      the biological mechanisms underlying these associations are warranted.

PMID- 29370363
TI  - Second cross-clamping after mitral valve repair for degenerative disease in
      contemporary practice.
AB  - OBJECTIVES: Scanty data are available on 'second cross-clamping' following mitral
      valve repair in contemporary practice. The aim of this study was to evaluate the
      incidence, causes and outcomes of this event in patients referred for mitral
      repair for severe degenerative mitral regurgitation (MR). METHODS: The study
      population included 2318 patients with severe degenerative MR referred for mitral
      repair. A second cross-clamping was performed in 94 (4%) patients. Causes of the
      second cross-clamping, revising repair procedures, immediate echocardiographic
      outcomes and postoperative course were assessed and compared with the 'single
      cross-clamping cases' (2224 patients used as control). Clinical and
      echocardiographic follow-up information was available for 91 of the 94 second
      cross-clamping patients (97% complete) (median time 6 years, interquartile range
      3-11). RESULTS: The most frequent causes of the second cross-clamping were
      residual MR >1+/4+ and systolic anterior motion. A residual prolapse was
      identified in 41 (43.5%) patients, systolic anterior motion in 22 (23.5%),
      untreated clefts in 14 (15%) and other mechanisms in 17 (18%). Second
      cardiopulmonary bypass and aortic cross-clamping times were 36 (range 28-50) and
      23 (range 17-34) min, respectively. Hospital mortality was 0% in the second cross
      clamping and 0.3% in the control group (P = 0.2). Postoperative complications and
      length of hospital stay were similar. At discharge, residual MR >=2+/4+ was 2.1%
      in the second cross-clamping and 2.7% in the control group (P = 0.99). In the
      second cross-clamping, at 12 years, the cumulative incidence function of
      reoperation, recurrent MR >=3+ and MR >=2+ with death as competing risk were 5.7
      +/- 2.5% (95% confidence interval 2-12), 10.3 +/- 4.3% (95% confidence interval
      3.8-20) and 17 +/- 5.2% (95% confidence interval 8-29), respectively.
      CONCLUSIONS: In a large volume centre for mitral repair, a second cross-clamping
      is still performed in 3-5% of the patients. Because suboptimal immediate results
      are associated with impaired late outcomes of mitral reconstruction, a low
      threshold for a second cross-clamping seems to be justified. If the second repair
      is carried out with a relatively shorter additional cross-clamping time,
      mortality and morbidity are not increased and immediate and long-term results are
      very satisfactory.

PMID- 29370364
TI  - Adherence of Clostridium perfringens spores to human intestinal epithelial Caco-2
      cells.
AB  - Clostridium perfringens is a gram-positive, spore-forming bacillus, and is a
      causative agent of foodborne infection, antibiotic-associated diarrhoea and
      sporadic diarrhoea in humans. In cases of antibiotic-associated and sporadic
      diarrhoea, C. perfringens colonises the intestine, proliferates and causes
      disease. However, bacterial colonisation of the intestine is not considered
      necessary in the pathogenesis of foodborne illness, because such pathogenesis can
      be explained by anchorage-independent production of diarrhoeic toxin by the
      bacterium in the intestine. In this study, we used an in vitro adherence assay to
      examine the adherence of C. perfringens spores to human intestinal Caco-2 cells.
      Adherence of spores from isolates of foodborne illness and nosocomial infection
      was observed within 15 min, and plateaued 60 min after inoculation. Electron
      microscopy revealed a tight association of spores with the surface of Caco-2
      cells. The adherence of vegetative cells could not be confirmed by the same
      method, however. These results suggest that C. perfringens spores may adhere to
      intestinal epithelial cells in vivo, although its biological significance remains
      to be determined.

PMID- 29370362
TI  - The pipe model theory half a century on: a review.
AB  - Background: More than a half century ago, Shinozaki et al. (Shinozaki K, Yoda K,
      Hozumi K, Kira T. 1964a. A quantitative analysis of plant form - the pipe model
      theory. I. Basic analyses. Japanese Journal of Ecology B: 97-105) proposed an
      elegant conceptual framework, the pipe model theory (PMT), to interpret the
      observed linear relationship between the amount of stem tissue and corresponding
      supported leaves. The PMT brought a satisfactory answer to two vividly debated
      problems that were unresolved at the moment of its publication: (1) What
      determines tree form and which rules drive biomass allocation to the foliar
      versus stem compartments in plants? (2) How can foliar area or mass in an
      individual plant, in a stand or at even larger scales be estimated? Since its
      initial formulation, the PMT has been reinterpreted and used in applications, and
      has undoubtedly become an important milestone in the mathematical interpretation
      of plant form and functioning. Scope: This article aims to review the PMT by
      going back to its initial formulation, stating its explicit and implicit
      properties and discussing them in the light of current biological knowledge and
      experimental evidence in order to identify the validity and range of
      applicability of the theory. We also discuss the use of the theory in tree
      biomechanics and hydraulics as well as in functional-structural plant modelling.
      Conclusions: Scrutinizing the PMT in the light of modern biological knowledge
      revealed that most of its properties are not valid as a general rule. The
      hydraulic framework derived from the PMT has attracted much more attention than
      its mechanical counterpart and implies that only the conductive portion of a stem
      cross-section should be proportional to the supported foliage amount rather than
      the whole of it. The facts that this conductive portion is experimentally
      difficult to measure and varies with environmental conditions and tree ontogeny
      might cause the commonly reported non-linear relationships between foliage and
      stem metrics. Nevertheless, the PMT can still be considered as a portfolio of
      properties providing a unified framework to integrate and analyse functional
      structural relationships.

PMID- 29370365
TI  - The effects of antimicrobial peptides WAM-1 and LL-37 on multidrug-resistant
      Acinetobacter baumannii.
AB  - Increasing multidrug resistance (MDR) in Acinetobacter baumannii warrants
      therapeutic alternatives, and the bactericidal nature of antimicrobial peptides
      (AMPs) offers a possible approach. In this study, we examined the interaction of
      cathelicidin AMPs WAM-1, a marsupial AMP, and LL-37, a human AMP, with A.
      baumannii clinical isolates. We characterized the antibiotic resistance of the
      isolates, the bacteriostatic and bactericidal effects of these AMPs, synergistic
      activity with antibiotics, and their effects on biofilm formation and dispersal.
      All clinical isolates were resistant to commonly prescribed antibiotics, with
      four of seven isolates showing MDR. WAM-1 and LL-37 showed variable activity in
      clinical isolates, with WAM-1 having a stronger bacteriostatic effect than LL-37
      and showing rapid bactericidal activity against clinical isolates. Furthermore,
      synergistic bactericidal activity was observed with WAM-1 and commonly prescribed
      antibiotics. Both peptides were able to inhibit biofilm formation in all clinical
      isolates at some concentrations, and WAM-1 dispersed mature biofilm in most
      isolates. LL-37 was unable to disperse mature biofilms in any strains. Further
      studies must be done to elucidate the true value of these alternative treatments,
      but these results suggest that MDR A. baumannii's susceptibility to AMPs may
      result in innovative therapeutics to prevent or treat these infections.

PMID- 29370366
TI  - National Patterns of Urine Testing During Inpatient Admission.
AB  - Background: Overuse of urine testing is a driver of inappropriate antimicrobial
      use. Limiting wasteful testing is important for patient safety. We examined the
      national prevalence and patterns of urine testing during adult inpatient
      admission in the United States. Methods: We performed a retrospective cohort
      study using a national dataset of inpatient admissions from 263 hospitals in the
      United States from 2009 to 2014. We included all adult inpatient admissions,
      excluding those related to pregnancy, urology procedures, and with lengths of
      stay >30 days. A facility-level fixed-effects quasi-Poisson regression model was
      used to examine the incidence of urinalysis and urine culture testing for select
      diagnoses and patient factors. Results: The cohort included 4473655 admissions.
      Charges for urinalysis were present for 2086697 (47%) admissions, with 584438
      (13%) including >1 urinalysis. Charges for urine culture were present for 1197242
      (27%) admissions, with 246211 (6%) having >1 culture. Urine culture testing
      varied by principal diagnosis. Heart failure and acute myocardial infarction had
      29% and 35% fewer cultures sent on the first day of admission compared to all
      other admissions (P < .001). Female sex and receipt of antibiotics during the
      hospital admission consistently predicted increased culture testing, regardless
      of principal diagnosis or age. Conclusions: Urine testing was common and
      frequently repeated during inpatient admission, suggesting large-scale overuse.
      The variation in testing by diagnosis suggests that clinical presentation
      modifies test use. The sex bias in urine testing is not clinically supported and
      must be addressed in interventions aimed at reducing excess urine testing.

PMID- 29370367
TI  - Minimally invasive aortic valve replacement through an upper hemisternotomy: the
      Vienna technique.
AB  - Minimally invasive approaches for aortic valve replacement are increasingly used
      in current clinical practice. Herein, we provide insights into our upper
      hemisternotomy approach with specific technical considerations and details.

PMID- 29370368
TI  - THE AUTHORS REPLY.

PMID- 29370369
TI  - Root cap-mediated evaluation of soil resistance towards graviresponding roots of
      maize (Zea mays L.) and the relevance of ethylene.
AB  - Background and Aims: Besides biological and chemical impacts, mechanical
      resistance represents an important obstacle that growing roots face.
      Graviresponding roots must assess the mechanical resistance of the substrate and
      take decisions on whether they change growth direction and grow around obstacles
      or tolerate growth conditions impaired to varying degrees. To test the
      significance of the root cap, we measured pressure and growth behaviour of single
      intact, as well as decapped, roots encountering diverse mechanical obstacles. We
      examined ethylene emission in intact roots as well as roots without a root cap,
      thereby lacking the capacity to deviate. Methods: Roots of fixed seedlings were
      grown vertically onto diverse mechanical obstacles. Developing pressure profiles
      of vertically growing roots encountering horizontal mechanical obstacles were
      measured employing electronic milligram scales, with and without root caps in
      given local environmental conditions. The evolution of root-borne ethylene was
      measured in intact roots and roots without the root cap. Key Results: In contrast
      to decapped roots, intact roots develop a tentative, short-lasting pressure
      profile, the resolution of which is characterized by a definite change of growth
      direction. Similarly, pressure profiles and strengths of roots facing gradually
      differing surface resistances differ significantly between the two. This
      correlates in the short term with root cap-dependent ethylene emission which is
      lacking in roots without caps. Conclusions: The way gravistimulated and
      graviresponding roots cope with exogenous stimuli depends on whether and how they
      adapt to these impacts. With respect to mechanical hindrances, roots without caps
      do not seem to be able to evaluate soil strengths in order to respond adequately.
      On encountering resistance, roots with intact caps emit ethylene, which is not
      observed in decapped roots. It therefore appears that it is the root cap which
      specifically orchestrates the resistance needed to overcome mechanical resistance
      by specifically inducing ethylene.

PMID- 29370370
TI  - Reply to Bazaz and Denning.

PMID- 29370371
TI  - Plasmids carrying antimicrobial resistance genes in Enterobacteriaceae.
AB  - Bacterial antimicrobial resistance (AMR) is constantly evolving and horizontal
      gene transfer through plasmids plays a major role. The identification of plasmid
      characteristics and their association with different bacterial hosts provides
      crucial knowledge that is essential to understand the contribution of plasmids to
      the transmission of AMR determinants. Molecular identification of plasmid and
      strain genotypes elicits a distinction between spread of AMR genes by plasmids
      and dissemination of these genes by spread of bacterial clones. For this reason
      several methods are used to type the plasmids, e.g. PCR-based replicon typing
      (PBRT) or relaxase typing. Currently, there are 28 known plasmid types in
      Enterobacteriaceae distinguished by PBRT. Frequently reported plasmids [IncF,
      IncI, IncA/C, IncL (previously designated IncL/M), IncN and IncH] are the ones
      that bear the greatest variety of resistance genes. The purpose of this review is
      to provide an overview of all known AMR-related plasmid families in
      Enterobacteriaceae, the resistance genes they carry and their geographical
      distribution.

PMID- 29370372
TI  - Does patient-prosthesis mismatch have a negative impact on outcomes following
      mitral valve replacement?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether patient-prosthesis mismatch (PPM)
      has a negative impact on patients undergoing mitral valve replacement in terms of
      postoperative mortality, incidence of postoperative pulmonary hypertension (PH)
      and higher transmitral gradients. Altogether 103 papers were found using the
      reported search, 18 of which represented the best evidence to answer the clinical
      question. The authors, journal, date and country of publication, patient group
      studied, study type, relevant outcomes and results of these papers are tabulated.
      Overall, 8 studies with a total of 4812 patients reported that PPM has a
      significantly negative impact on long-term mortality, whereas 5 studies with a
      total of 1558 patients reported no effect on mortality. One study with a total of
      2440 patients reported preoperative PH as the risk factor for increased mortality
      in the presence of moderate or severe PPM. Three studies evaluated the effect of
      PPM on postoperative PH and reported that PPM was associated with significantly
      increased postoperative PH. The majority of the studies reported that PPM was
      associated with higher peak or mean transmitral gradient and systolic pulmonary
      artery pressure. The results presented in these studies suggest that PPM in
      patients undergoing mitral valve replacement was associated with increased
      postoperative mean and peak transmitral gradient and higher postoperative
      systolic pulmonary artery pressure. PPM may be associated with increased long
      term mortality. Severe PPM was directly associated with increased long-term
      mortality when compared with moderate or no PPM. Evidence suggests that PPM is
      associated with increased incidence of postoperative PH.

PMID- 29370373
TI  - Risks of Antimicrobial Resistance in N. gonorrhoeae Associated with Intensive
      Screening Programs in Pre-Exposure Prophylaxis Programs.

PMID- 29370374
TI  - Evolution of nectar spur length in a clade of Linaria reflects changes in cell
      division rather than in cell expansion.
AB  - Background and Aims: Nectar spurs (tubular outgrowths of a floral organ which
      contain, or give the appearance of containing, nectar) are hypothesized to be a
      'key innovation' which can lead to rapid speciation within a lineage, because
      they are involved in pollinator specificity. Despite the ecological importance of
      nectar spurs, relatively little is known about their development. We used a
      comparative approach to investigate variation in nectar spur length in a clade of
      eight Iberian toadflaxes. Methods: Spur growth was measured at the macroscopic
      level over time in all eight species, and growth rate and growth duration
      compared. Evolution of growth rate was reconstructed across the phylogeny. Within
      the clade we then focused on Linaria becerrae and Linaria clementei, a pair of
      sister species which have extremely long and short spurs, respectively.
      Characterization at a micromorphological level was performed across a range of
      key developmental stages to determine whether the difference in spur length is
      due to differential cell expansion or cell division. Key Results: We detected a
      significant difference in the evolved growth rates, while developmental timing of
      both the initiation and the end of spur growth remained similar. Cell number is
      three times higher in the long spurred L. becerrae compared with L. clementei,
      whereas cell length is only 1.3 times greater. In addition, overall anisotropy of
      mature cells is not significantly different between the two species. Conclusions:
      We found that changes in cell number and therefore in cell division largely
      explain evolution of spur length. This contrasts with previous studies in
      Aquilegia which have found that variation in nectar spur length is due to
      directed cell expansion (anisotropy) over variable time frames. Our study adds to
      knowledge about nectar spur development in a comparative context and indicates
      that different systems may have evolved nectar spurs using disparate mechanisms.

PMID- 29370375
TI  - Cohort Profile: The Siyakhula Cohort, rural South Africa.

PMID- 29370376
TI  - Development of a secondary electron energy analyzer for a transmission electron
      microscope.
AB  - A secondary electron (SE) energy analyzer was developed for a transmission
      electron microscope. The analyzer comprises a microchannel plate (MCP) for
      detecting electrons, a coil for collecting SEs emitted from the specimen, a tube
      for reducing the number of backscattered electrons incident on the MCP, and a
      retarding mesh for selecting the energy of SEs incident on the MCP. The detection
      of the SEs associated with charging phenomena around a charged specimen was
      attempted by performing electron holography and SE spectroscopy using the energy
      analyzer. The results suggest that it is possible to obtain the energy spectra of
      SEs using the analyzer and the charging states of a specimen by electron
      holography simultaneously.

PMID- 29370378
TI  - Soft X-ray emission spectroscopy study of electronic structure of sodium
      borosilicide Na8B74.5Si17.5.
AB  - Chemical bonding state of sodium borosilicide Na8B74.5Si17.5, which is a new
      member of B12-cluster materials, is investigated by soft X-ray emission
      spectroscopy. The material is composed of B12 cluster network and characteristic
      silicon chains of [-Si-(Si-Si)3-Si-] connected by sp3 bonding, in which bonding
      distances and bonding angles are close to those in cubic Si crystal. B K-emission
      spectrum of the material showed a similar but a broader intensity distribution
      with those of B12 cluster materials of alpha-r-B, B4C and beta-r-B. The broader
      intensity distribution can be due to a variation of B-B bond length in B12
      cluster. The density of states (DOS) of silicon chains of [-Si-(Si-Si)3-Si-] was
      experimentally derived. It shows a similar energy width, and peak or shoulder
      structures in intensity distribution with those of L-emission spectrum of cubic
      Si. From comparisons between experimental spectra and corresponding calculated
      DOS, covalent bonding between Si chain and B12 cluster network is suggested.
      Those are discussed by using a theoretically calculated density of state of
      Na8B74.5Si17.5 by using WIEN2k code.

PMID- 29370379
TI  - Glycan-directed CAR-T cells.
AB  - Cancer immunotherapy is rapidly advancing in the treatment of a variety of
      hematopoietic cancers, including pediatric acute lymphoblastic leukemia and
      diffuse large B cell lymphoma, with chimeric antigen receptor (CAR)-T cells. CARs
      are genetically encoded artificial T cell receptors that combine the antigen
      specificity of an antibody with the machinery of T cell activation. However,
      implementation of CAR technology in the treatment of solid tumors has been
      progressing much slower. Solid tumors are characterized by a number of challenges
      that need to be overcome, including cellular heterogeneity, immunosuppressive
      tumor microenvironment (TME), and, in particular, few known cancer-specific
      targets. Post-translational modifications that differentially occur in malignant
      cells generate valid cell surface, cancer-specific targets for CAR-T cells. We
      previously demonstrated that CAR-T cells targeting an aberrant O-glycosylation of
      MUC1, a common cancer marker associated with changes in cell adhesion, tumor
      growth and poor prognosis, could control malignant growth in mouse models. Here,
      we discuss the field of glycan-directed CAR-T cells and review the different
      classes of antibodies specific for glycan-targeting, including the generation of
      high affinity O-glycopeptide antibodies. Finally, we discuss historic and
      recently investigated glycan targets for CAR-T cells and provide our perspective
      on how targeting the tumor glycoproteome and/or glycome will improve CAR-T
      immunotherapy.

PMID- 29370380
TI  - Prenatal Dexamethasone Exposure Induced Ovarian Developmental Toxicity and
      Transgenerational Effect in Rat Offspring.
AB  - Prenatal dexamethasone exposure (PDE) induces multiorgan developmental toxicities
      in offspring. Here we verified the transgenerational inheritance effect of
      ovarian developmental toxicity by PDE and explored its intrauterine programming
      mechanism. Pregnant rats subcutaneously received 0.2 mg/kg/d dexamethasone from
      gestational day (GD) 9 to GD20. A subgroup was euthanized for fetuses on GD20,
      and the other group went on to spontaneous labor to produce F1 offspring. The
      adult F1 females were mated with normal males to produce the F2 and F3
      generations. The PDE fetal rats exhibited ovarian mitochondrial structural
      abnormalities, decreased serum estradiol (E2) levels, and lower expression levels
      of ovarian steroidogenic factor 1 (SF1), steroidal synthetases, and insulinlike
      growth factor 1 (IGF1). On postnatal week (PW) 6 and PW12, the PDE F1 offspring
      showed altered reproductive behavior and ovarian morphology. The serum E2 level
      and ovarian expression of SF1, steroidal synthetases, and IGF1 were also
      decreased. The adult F3 offspring showed alterations in reproductive phenotype
      and ovarian IGF1, SF1, and steroidal synthetase expression similar to those of
      F1. PDE induces ovarian developmental toxicity and transgenerational inheritance
      effects. The mechanism by which this toxicity occurs may be related to PDE
      induced low-functional programming of fetal ovarian IGF1/SF1 and steroidal
      synthetases.

PMID- 29370377
TI  - Big data from electronic health records for early and late translational
      cardiovascular research: challenges and potential.
AB  - Aims: Cohorts of millions of people's health records, whole genome sequencing,
      imaging, sensor, societal and publicly available data present a rapidly expanding
      digital trace of health. We aimed to critically review, for the first time, the
      challenges and potential of big data across early and late stages of
      translational cardiovascular disease research. Methods and results: We sought
      exemplars based on literature reviews and expertise across the BigData@Heart
      Consortium. We identified formidable challenges including: data quality, knowing
      what data exist, the legal and ethical framework for their use, data sharing,
      building and maintaining public trust, developing standards for defining disease,
      developing tools for scalable, replicable science and equipping the clinical and
      scientific work force with new inter-disciplinary skills. Opportunities claimed
      for big health record data include: richer profiles of health and disease from
      birth to death and from the molecular to the societal scale; accelerated
      understanding of disease causation and progression, discovery of new mechanisms
      and treatment-relevant disease sub-phenotypes, understanding health and diseases
      in whole populations and whole health systems and returning actionable feedback
      loops to improve (and potentially disrupt) existing models of research and care,
      with greater efficiency. In early translational research we identified exemplars
      including: discovery of fundamental biological processes e.g. linking exome
      sequences to lifelong electronic health records (EHR) (e.g. human knockout
      experiments); drug development: genomic approaches to drug target validation;
      precision medicine: e.g. DNA integrated into hospital EHR for pre-emptive
      pharmacogenomics. In late translational research we identified exemplars
      including: learning health systems with outcome trials integrated into clinical
      care; citizen driven health with 24/7 multi-parameter patient monitoring to
      improve outcomes and population-based linkages of multiple EHR sources for higher
      resolution clinical epidemiology and public health. Conclusion: High volumes of
      inherently diverse ('big') EHR data are beginning to disrupt the nature of
      cardiovascular research and care. Such big data have the potential to improve our
      understanding of disease causation and classification relevant for early
      translation and to contribute actionable analytics to improve health and
      healthcare.

PMID- 29370382
TI  - Honey, I Shrunk the Antibiotic Therapy.

PMID- 29370381
TI  - Ablation of Grb10 Specifically in Muscle Impacts Muscle Size and Glucose
      Metabolism in Mice.
AB  - Grb10 is an adaptor-type signaling protein most highly expressed in tissues
      involved in insulin action and glucose metabolism, such as muscle, pancreas, and
      adipose. Germline deletion of Grb10 in mice creates a phenotype with larger
      muscles and improved glucose homeostasis. However, it has not been determined
      whether Grb10 ablation specifically in muscle is sufficient to induce
      hypermuscularity or affect whole body glucose metabolism. In this study we
      generated muscle-specific Grb10-deficient mice (Grb10-mKO) by crossing
      Grb10flox/flox mice with mice expressing Cre recombinase under control of the
      human alpha-skeletal actin promoter. One-year-old Grb10-mKO mice had enlarged
      muscles, with greater cross-sectional area of fibers compared with wild-type (WT)
      mice. This degree of hypermuscularity did not affect whole body glucose
      homeostasis under basal conditions. However, hyperinsulinemic/euglycemic clamp
      studies revealed that Grb10-mKO mice had greater glucose uptake into muscles
      compared with WT mice. Insulin signaling was increased at the level of phospho
      Akt in muscle of Grb10-mKO mice compared with WT mice, consistent with a role of
      Grb10 as a modulator of proximal insulin receptor signaling. We conclude that
      ablation of Grb10 in muscle is sufficient to affect muscle size and metabolism,
      supporting an important role for this protein in growth and metabolic pathways.

PMID- 29370384
TI  - Erratum.

PMID- 29370383
TI  - Circadian variation of ticagrelor-induced platelet inhibition in healthy adulty.
AB  - Aims: The circadian variation of platelet aggregation is well demonstrated.
      However, whether this has an impact on antiplatelet inhibition therapy is poorly
      documented. We aimed to observe whether ticagrelor-induced platelet inhibition
      follows a circadian rhythm. Methods and results: The study included 25 healthy
      volunteers (11 female; 14 male). Blood samples were collected every 4 h.
      Ticagrelor was added in vitro at a concentration that provided 50% inhibition of
      the maximum response using the VerifyNow System Platelet Reactivity Test(r) thus
      avoiding any bias induced by circadian gastrointestinal absorption. Platelet
      aggregation testing was subsequently performed using the VerifyNow. Circadian
      changes in total platelet count, percentage of platelets inhibition, Von
      Willebrand activity, and volunteers' physiological parameters were analysed by
      fitting individuals' data to a sine curve with a 24-h period. Volunteers'
      physiological parameters [heart rate (b.p.m.), systolic/diastolic blood pressure
      (mmHg), and body temperature (Celsius)] followed a significant mean circadian
      pattern of 6 b.p.m. (P < 0.001), 5 mmHg/7 mmHg (P < 0.002), and 0.3 degrees C (P
      < 0.001), respectively. Ticagrelor-induced platelet inhibition was significantly
      lower at 13:00 (38.4%) than at any other time (45.2%) (P = 0.018). Percentage of
      inhibited platelets plotted against time followed a circadian rhythm (P < 0.001),
      with mean minimum/maximum values at 13:00/02:00, respectively. Von Willebrand
      activity also followed a circadian pattern (P < 0.001), with an amplitude of
      12.24% and a maximum activity at 12:00. Conclusion: Ticagrelor-induced platelet
      inhibition follows a circadian rhythm, with the lowest mean values achieved at
      13:00. These results deserve further studies in patients with coronary artery
      disease.

PMID- 29370385
TI  - Profligate and conservative: water use strategies in grain legumes.
AB  - Yields of grain legumes are constrained by available water. Thus, it is crucial
      to understand traits influencing water uptake and the efficiency of using water
      to produce biomass. Global comparisons and comparisons at specific locations
      reveal that water use of different grain legumes is very similar, which indicates
      that water use efficiency varies over a wide range due to differences in biomass
      and yield. Moreover, yield increases more per millimetre of water used in cool
      season grain legumes than warm season species. Although greater contrasts have
      been observed across species and genotypes at the pot and lysimeter level,
      agronomic factors need to be taken into account when scaling those studies to
      field-level responses. Conservative water use strategies in grain legumes such as
      low stomatal conductance as approximated by low photosynthetic carbon isotope
      discrimination reduces yield potential, whereas temporal adjustments of stomatal
      conductance within the growing season and in response to environmental factors
      (such as vapour pressure deficit) helps to optimize the trade-off between carbon
      gain and water loss. Furthermore, improved photosynthetic capacity, reduced
      mesophyll conductance, reduced boundary layer, and re-fixation of respired CO2
      were identified as traits that are beneficial without water deficit, but also
      under terminal and transient drought. Genotypic variability in some grain legume
      species has been observed for several traits that influence water use, water use
      efficiency, and yield, including root length and the temporal pattern of water
      use, but even more variation is expected from wild relatives. Albeit that N2
      fixation decreases under drought, its impact on water use is still largely
      unknown, but the nitrogen source influences gas exchange and, thus, transpiration
      efficiency. This review concludes that conservative traits are needed under
      conditions of terminal drought to help maintain soil moisture until the pod
      filling period, but profligate traits, if tightly regulated, are important under
      conditions of transient drought in order to profit from short intermittent
      periods of available soil moisture.

PMID- 29370386
TI  - Quantitative imaging of plants: multi-scale data for better plant anatomy.

PMID- 29370387
TI  - A new opening for wheat seed production.

PMID- 29370388
TI  - Corrigendum: Crop-model assisted phenomics and genome-wide association study for
      climate adaptation of indica rice. 1. Phenology.

PMID- 29370389
TI  - Corrigendum: Crop-model assisted phenomics and genome-wide association study for
      climate adaptation of indica rice 2. Thermal stress and spikelet sterility.

PMID- 29370390
TI  - Egg CD9 protein tides correlated with sperm oscillations tune the gamete fusion
      ability in mammal.
AB  - Mammalian fertilization involves membrane events -adhesion, fusion, sperm
      engulfment, membrane block to polyspermy- whose causes remain largely unknown.
      Recently, specific oscillations of the sperm in contact with the egg were shown
      to be necessary for fusion. Using a microfluidic chip to impose the venue for the
      encounter of two gametes allowed real-time observation of the membrane
      remodelling occurring at the sperm/egg interface. The spatiotemporal mapping of
      egg CD9 revealed that this protein concentrates at the egg/sperm interface as a
      result of sperm oscillations, until a CD9-rich platform is nucleated on which
      fusion immediately takes place. Within 2 to 5 minutes after fusion, most of the
      CD9 leaves the egg for the external aqueous medium. Then an egg membrane wave
      engulfs the sperm head in approximately 25 minutes. These results show that sperm
      oscillations initiate the CD9 recruitment that causes gamete fusion after which
      CD9 and associated proteins leave the membrane in a process likely to contribute
      to block polyspermy. They highlight that the gamete fusion story in mammals is an
      unexpected interplay between mechanical constraints and proteins.

PMID- 29370391
TI  - Leaflet detachment in a Carpentier-Edwards Perimount Magna mitral pericardial
      valve bioprosthesis.

PMID- 29370392
TI  - Subacute Invasive Aspergillosis Associated With Sorafenib Therapy for
      Hepatocellular Carcinoma.

PMID- 29370393
TI  - The impact of ART on union dissolution: a register-based study in Denmark 1994
      2010.
AB  - STUDY QUESTION: Are couples initiating ART treatment at higher risk for future
      union dissolution compared to other couples? SUMMARY ANSWER: There is no effect
      of ART treatments in future marital dissolution over a period of 16 years when
      adjusting for all confounders. WHAT IS KNOWN ALREADY: Findings regarding marital
      stability and infertility treatments have been sparse and controversial. While
      there is data showing higher divorce rates among women who go through infertility
      treatments, there is also some evidence of this experience bringing couples
      closer by forcing them to communicate more and to deal with the surrounding
      stigma. Using a population-based study and couple-level data, we investigated the
      extent to which ART treatment increases the risk for divorce/marital dissolution
      during up to 16 years of follow-up. STUDY DESIGN SIZE, DURATION: Register-based
      national cohort study including all women registered with ART treatment in
      Denmark between 1 January 1994 and 30 September 2009 (n = 42 845).
      Marital/cohabiting status was confirmed by matching these women to partners who
      they were married to or shared an address with. To account for having a
      significant relationship at baseline (2 years), marital/cohabiting status was
      confirmed by accessing this variable before the establishment of the cohort back
      to 1 January 1992. PARTICIPANTS/MATERIALS, SETTING, METHODS: A comparison group
      from the background population including five controls per case and matched to
      female age at baseline was prospectively sampled. Participants could change
      status during follow-up if they entered ART. The final sample had 148 972
      couples, followed until marital dissolution, death of self/spouse, migration or
      until 31 December 2010. We used Cox regression models adjusting for female and
      male age, education, marriage, common child at baseline and live-born child
      during follow-up. MAIN RESULTS AND THE ROLE OF CHANCE: At baseline, the majority
      of couples were married (69%). More non-ART couples opted for marriage (70%
      versus 64%; P < 0.0001) and already had common children at study entry (43%
      versus 9%; P < 0.0001). During the 16 years of follow-up the majority of couples
      had children with their baseline partners (56% non-ART versus 65% ART), and 22%
      ended up separated or divorced (20% ART versus 22% non-ART). Findings revealed a
      lower risk of break-up among ART couples (crude HR 0.84, 95% CI 0.82-0.86), even
      after adjusting for both partners' age, education, partnership status and having
      a common child at baseline (adj HR 0.83, 95% CI 0.80-0.86). However, when
      subsequent common children (time-dependent) was added to the model, no difference
      in the risk of dissolution was found (adj HR 1.00, 95% CI 0.99-1.01). A
      significant interaction between ART status and common children showed that the
      risk of break-up was attributed to childlessness regardless of having gone
      through ART treatment. LIMITATIONS REASON FOR CAUTION: This study did not control
      for involuntary childlessness, non-ART fertility care (ovulation induction, IUI)
      and biological parenthood. Additionally, there are important predictors of
      divorce that were not considered. We were unable to adjust for religion,
      existence of previous marital relationships, income, employment, health status of
      parents and child(ren), and quality of relationship. WIDER IMPLICATION OF
      FINDINGS: The finding that going through ART does not increase the risk of break
      up per se is reassuring for couples who underwent ART and have children or are
      contemplating to start ART. STUDY FUNDING/COMPETING INTEREST(S): This work was
      supported by FCT (Portuguese Foundation for Science and Technology), grant ref.
      SFRH/BPD/85789/2012. The authors have no conflicts of interest. TRIAL
      REGISTRATION NUMBER: N/A.

PMID- 29370395
TI  - Erratum.

PMID- 29370394
TI  - Convergent-beam EMCD: benefits, pitfalls and applications.
AB  - Energy-loss magnetic chiral dichroism (EMCD) is a versatile method for studying
      magnetic properties on the nanoscale. However, the classical EMCD technique is
      notorious for its low signal-to-noise ratio (SNR), which is why many
      experimentalists have adopted a convergent-beam approach. Here, we study the
      theoretical possibilities of using a convergent beam for EMCD. In particular, we
      study the influence of detector positioning as well as convergence and collection
      angles on the detectable EMCD signal. In addition, we analyse the expected SNR
      and give some guidelines for achieving optimal EMCD results.

PMID- 29370396
TI  - Ketamine-Induced Prefrontal Serotonin Release Is Mediated by Cholinergic Neurons
      in the Pedunculopontine Tegmental Nucleus.
AB  - Background: Ketamine rapidly elicits antidepressive effects in humans and mice in
      which serotonergic activity is involved. Although alpha4beta2 nicotinic
      acetylcholine receptor (alpha4beta2 nAChR) in the dorsal raphe nucleus plays a
      key role in the ketamine-induced prefrontal serotonin release, the source of
      cholinergic afferents, and its role is unclear. Methods: Prefrontal serotonin
      levels after ketamine injection were measured by microdialysis in rats.
      Electrolytic lesion of pedunculopontine tegmental nucleus and laterodorsal
      tegmental nucleus was made with constant direct current. Results: Bilateral
      lesion of the pedunculopontine tegmental nucleus, but not laterodorsal tegmental
      nucleus, attenuated prefrontal serotonin release induced by systemic ketamine.
      Intra-pedunculopontine tegmental nucleus, but not intra-laterodorsal tegmental
      nucleus ketamine perfusion, increased prefrontal serotonin release. This increase
      was attenuated by intra-dorsal raphe nucleus injection of dihydro-beta
      erythroidine, an alpha4beta2 nAChR antagonist, or NBQX, an AMPA receptor
      antagonist. Conclusions: These results suggest the ketamine-induced serotonin
      release in medial prefrontal cortex is mediated by cholinergic neurons projecting
      from pedunculopontine tegmental nucleus to dorsal raphe nucleus via alpha4beta2
      nAChRs.

PMID- 29370397
TI  - Primary Non-Response to Tumor Necrosis Factor Antagonists is Associated with
      Inferior Response to Second-line Biologics in Patients with Inflammatory Bowel
      Diseases: A Systematic Review and Meta-analysis.
AB  - Background and Aims: We sought to analyze whether response to a second-line
      biologic varies depending on the reason for discontinuation of the primary anti
      TNF agent (primary non-response [PNR], secondary loss of response [LOR] after
      initial response, or intolerance), through a systematic review and meta-analysis.
      Methods: Through a systematic search through May 31, 2017, we identified eight
      randomized controlled trials [RCTs] of biologics in patients with IBD with prior
      exposure to anti-TNF agents, that stratified response to second-line therapy by
      reason for discontinuing primary anti-TNF therapy [PNR vs. LOR vs. intolerance].
      We estimated relative risk [RR] (and 95% confidence interval [CI]) of achieving
      clinical remission in patients with PNR as compared with patients with LOR, and
      intolerance, through random effects meta-analysis. Results: As compared with
      patients who discontinued prior anti-TNF due to intolerance, patients with prior
      PNR were 24% less likely to achieve remission with second-line biologics (RR,0.76
      [0.61-0.96]). As compared with patients who discontinued prior anti-TNF due to
      LOR, patients with prior PNR were 27% less likely to achieve remission with
      induction therapy with second-line biologics (RR,0.73 [0.56-0.97]), particularly
      to ustekinumab (RR,0.64 [0.52-0.80]). There was no difference in response to
      vedolizumab in patients with prior PNR or LOR to anti-TNF agents (RR,1.16 [0.85
      1.58]). Conclusion: Patients with PNR to anti-TNF agents are less likely to
      respond to second-line non-TNF biologics, as compared with patients who
      discontinued therapy due to secondary LOR or intolerance. This may be attributed
      to underlying pharmacokinetics and pharmacodynamics of anti-TNF agents in
      patients with PNR.

PMID- 29370398
TI  - Heterologous expression, characterization and possible functions of the chitin
      deacetylases, Cda1 and Cda2, from mushroom Coprinopsis cinerea.
AB  - Two chitin deacetylases, Cda1 and Cda2, from Coprinopsis cinerea were expressed
      and characterized. Cda1 preferably deacetylates the nonreducing end residue of
      (GlcNAc)2, the internal or nonreducing end residue of (GlcNAc)3 and the
      nonreducing residue of (GlcNAc)6 after deacetylating the internal residues. In
      contrast, Cda2 preferably deacetylates the reducing end residue of (GlcNAc)2, the
      internal or reducing end residue of (GlcNAc)3 and the reducing residue of
      (GlcNAc)6 after deacetylating the internal residues. Furthermore, Cda1 prefers
      chitohexaose with higher degrees of acetylation for deacetylation, while Cda2
      shows a weaker preference for chitohexaose with varying degrees of acetylation.
      The predicted Cda1 structure shows more hydrophobic aromatic amino acids on the
      surface near subsite +1 in the active site than on the surface near subsite -1,
      whereas the predicted Cda2 structure has more hydrophobic aromatic amino acids on
      the surface near subsite -1 than on the surface near subsite +1, which may be the
      molecular basis of the distinctive catalytic features between Cda1 and Cda2.
      Notably, Cda1 has a high transcription level in the nonelongating basal stipe
      region, whereas Cda2 has a high transcription level in the elongating apical
      stipe region, and the transcription level of the former is approximately five
      times that of the latter. Correspondingly, the molar ratio of GlcN/GlcNAc
      increased from 0.15 in the cell wall of the apical stipe region to 0.22 in the
      cell wall of the basal stipe region. Different modes of action of Cda1 and Cda2
      may be related to their functions in the different stipe regions.

PMID- 29370399
TI  - Survival analysis of orthodontic retainers.
AB  - Objective: Retainers play a critical role in the long-term success of orthodontic
      treatment. The aims of this study were to evaluate the survival time of different
      retainers and to investigate the potential predictors of the retainer failures.
      Material and methods: A total of 591 retainers from 309 patients (between 2003
      and 2014) were included in the study, including Hawley retainers (n = 199),
      vacuum-formed retainers (n = 34), lingual fixed retainers (n = 278), and the
      COMBO (a combination of two different retainers in the same arch; n = 80).
      Patient's demographics, retention procedures, time to failure (survival time),
      and reasons for failures were extracted from patient files. Failure of retainer
      was defined as any events after which the retainers needed to be replaced or
      repaired; loss of retainer was treated as a failure because the retainer could
      not fulfil its role. Survival analyses were performed to compare the survival
      time between different retainer groups. Results: The survival time was the
      longest for lingual fixed retainers (median 1604 days) and Hawley retainers (1529
      days), followed by COMBO (258 days) and vacuum-formed retainers (105 days;
      overall P < 0.001). No statistical significance of survival time of lingual fixed
      retainers was found between maxilla (1497 days) and mandible (1604 days; P =
      0.341), nor between different types of the COMBO (overall P = 0.078). These
      results were unchanged before and after adjusting for the age, gender, and
      socioeconomic status (SES) of the patients. The reasons for failures varied among
      different retainers: most failures of the Hawley retainers were 'lost' (52.0%),
      most failures of the lingual fixed retainers were debond (63.5%), and fracture
      was the most common cause of failure for both vacuum-formed retainers (43.5%) and
      the COMBO (41.9%). Conclusion: Lingual fixed retainers and Hawley retainers had
      the longest survival times, followed by the COMBO retainers and vacuum-formed
      retainers. The reasons of failure were mainly mechanical (debond and fracture)
      and patient-related (loss).

PMID- 29370400
TI  - The interval between brainstem death and cardiac assessment influences the
      retrieval of hearts for transplantation.
AB  - OBJECTIVES: The optimum time after brainstem death (BSD) at which to assess the
      function of donor hearts is unknown. We hypothesized that a longer interval may
      be associated with a higher transplantation rate due to improved function.
      METHODS: Data were obtained from the UK Transplant Registry for the period
      between April 2010 and March 2015. The time when fixed dilated pupils were first
      noted in the donor was considered as the time of BSD. Retrieval was defined as
      the time when the abdominal organs were surgically perfused. RESULTS: BSD to
      retrieval duration was available for 1947 donors, of which 458 (24%) donated
      their heart. In the univariable analysis (not adjusting other donor risk
      factors), evidence was available to suggest that the BSD to cardiac assessment
      duration had a non-linear association with heart utilization (P < 0.0001).
      Adjusting for donor risk factors, the relationship remained with longer intervals
      being associated with increased transplantation (P = 0.0056). The modelled
      probability of heart utilization had a similar pattern to the observed rate of
      heart utilization. However, the probability of heart donation began to plateau
      after approximately 48 h. The analysis of the subset of donors attended by a
      cardiothoracic retrieval team showed a similar pattern. CONCLUSIONS: These data
      suggest that time interval from BSD to organ retrieval influences the heart
      retrieval rate. When the sole reason for declining a donor heart is poor
      function, a period of further observation and optimization up to 2 days should be
      considered.

PMID- 29370401
TI  - Combined smoking cues enhance reactivity and predict immediate subsequent
      smoking.
AB  - Introduction: Cue reactivity (CR) research has reliably demonstrated robust cue
      induced responding among smokers exposed to common proximal smoking cues (e.g.,
      cigarettes, lighter). More recent work demonstrates that distal stimuli, most
      notably the actual environments in which smoking previously occurred, can also
      gain associative control over craving. In the real world proximal cues always
      occur within an environment; thus, a more informative test of how cues affect
      smokers might be to present these two cue types simultaneously. Methods: Using a
      combined-cue counterbalanced cue reactivity paradigm, the present study tested
      the impact of proximal (smoking and neutral) + personal environment (smoking and
      nonsmoking places) pictorial cues, on smokers' subjective and behavioral cue
      reactivity; as well as the extent to which cue-induced craving predicts immediate
      subsequent smoking in a within-subjects design. Results: As anticipated, the dual
      smoking cue combination (ProxS+EnvS) led to the greatest cue-induced craving
      relative to the other three cue combinations (ProxS+EnvN, ProxN+EnvS, ProxN+
      EnvN), p's < .004. Dual smoking cues also led to significantly shorter post-trial
      latencies to smoke, p's < .01. Overall cue reactivity difference score (post
      trial craving minus baseline craving) was predictive of subsequent immediate
      smoking indexed by: Post-trial latency to smoke (B= -2.69, SE= 9.02; t(143) = 
      2.98, p = .003); total puff volume (B= 2.99, SE= 1.13; t(143)= 2.65, p = .009);
      and total number of puffs (B= .053, SE= .027; t(143)= 1.95, p = .05).
      Conclusions: The implications of these findings for better understanding the
      impact of cues on smoking behavior and cessation are discussed. Implications:
      This novel cue reactivity study examined smokers' reactivity to combined proximal
      and distal smoking cues. Exposure to a combination of two smoking cues (proximal
      and environment) led to the greatest increases in cue-induced craving and smoking
      behavior compared to all other cue combinations. Further, the overall magnitude
      of cue-induced craving was found to significantly predict immediate subsequent
      smoking. This work provides new insight on how exposure to various cues and cue
      combinations directly affect smokers' craving and actual smoking behavior, as
      well as the relationship between those two indices of reactivity.

PMID- 29370402
TI  - Molecular epidemiology and phylogenetic analysis of fowl adenoviruses caused
      hydropericardium outbreak in China during 2015.
AB  - An outbreak of hydropericardium syndrome has been ongoing in East China since
      2015. To decipher the disease etiology, 26 full-length sequences of the
      adenovirus hexon gene were cloned and sequenced. Phylogenetic trees and sequence
      alignments revealed that all 26 strains belonged to subgroup C serotype 4 and
      shared some consistent molecular characteristics that showed only 9 mutations
      without amino acid (AA) deletions. Eight sites were located in L1 and one in L2.
      To determine whether the complete hexon gene was under positive selection
      pressure, site-by-site analysis was performed to identify specific codons that
      underwent evolutionary selection. Analysis identified 7 positively selected
      codons in L1 (AA 164, 168, 195, and 243) and L2 (AA 379, 402, and 408). The other
      2 sites (AA 140 and 680) were located in P1 and P2, respectively. The results
      reveal that hexon loops L1 and L2 are hypervariable regions. Moreover,
      elucidation of viral distribution indicated that the liver is a major target
      organ, and FAdV-4 is a pantropic virus. In summary, FAdV-4 has been identified as
      an epidemic strain, and viral evolution is ongoing; thus, continuous surveillance
      of this virus will contribute to the control of future epidemics.

PMID- 29370403
TI  - Fucose-specific lectin of Aspergillus fumigatus: binding properties and effects
      on immune response stimulation.
AB  - Aspergillus fumigatus is the major causative fungus of aspergillosis, and many
      studies have explored the relationship between A. fumigatus and pathogenicity. In
      the current study, we focused on a fucose-specific lectin, FleA, as a novel
      molecule which related to the pathogenicity of A. fumigatus. The disruption of
      the fleA gene did not lead to clear morphological changes compared to parental
      strain under several stress conditions in culture, but germination become
      earlier. In comparison with parental strain, the pathogenicity of disruptant was
      enhanced in a mouse infection model. The pattern of conidial phagocytosis and
      adhesion to cultured cells did not explain this enhanced pathogenicity. FleA was
      reported to contain six conserved fucose-binding sites; the analysis of
      constructed FleA point mutants revealed nonequivalent contribution of the fucose
      binding sites to fucose binding. Based on the immune response induced in the
      cultured cells upon exposure to wild-type and mutant FleA, we propose a model of
      the FleA molecule in A. fumigatus infection.

PMID- 29370404
TI  - Negative Symptoms in Early-Onset Psychosis and Their Association With
      Antipsychotic Treatment Failure.
AB  - The prevalence of negative symptoms (NS) at first episode of early-onset
      psychosis (EOP), and their effect on psychosis prognosis is unclear. In a sample
      of 638 children with EOP (aged 10-17 y, 51% male), we assessed (1) the prevalence
      of NS at first presentation to mental health services and (2) whether NS
      predicted eventual development of multiple treatment failure (MTF) prior to the
      age of 18 (defined by initiation of a third trial of novel antipsychotic due to
      prior insufficient response, intolerable adverse-effects or non-adherence). Data
      were extracted from the electronic health records held by child inpatient and
      community-based services in South London, United Kingdom. Natural Language
      Processing tools were used to measure the presence of Marder Factor NS and
      antipsychotic use. The association between presenting with >=2 NS and the
      development of MTF over a 5-year period was modeled using Cox regression. Out of
      the 638 children, 37.5% showed >=2 NS at first presentation, and 124 (19.3%)
      developed MTF prior to the age of 18. The presence of NS at first episode was
      significantly associated with MTF (adjusted hazard ratio 1.62, 95% CI 1.07-2.46;
      P = .02) after controlling for a number of potential confounders including
      psychosis diagnostic classification, positive symptoms, comorbid depression, and
      family history of psychosis. Other factors associated with MTF included comorbid
      autism spectrum disorder, older age at first presentation, Black ethnicity, and
      family history of psychosis. In EOP, NS at first episode are prevalent and may
      help identify a subset of children at higher risk of responding poorly to
      antipsychotics.

PMID- 29370405
TI  - Oviductal extracellular vesicles (oviductosomes, OVS) are conserved in humans:
      murine OVS play a pivotal role in sperm capacitation and fertility.
AB  - STUDY QUESTIONS: Are extracellular vesicles (EVs) in the murine oviduct
      (oviductosomes, OVS) conserved in humans and do they play a role in the fertility
      of Pmca4-/- females? SUMMARY ANSWER: OVS and their fertility-modulating proteins
      are conserved in humans, arise via the apocrine pathway, and mediate a
      compensatory upregulation of PMCA1 (plasma membrane Ca2+-ATPase 1) in Pmca4-/-
      female mice during proestrus/estrus, to account for their fertility. WHAT IS
      KNOWN ALREADY: Recently murine OVS were identified and shown during
      proestrus/estrus to express elevated levels of PMCA4 which they can deliver to
      sperm. PMCA4 is the major Ca2+ efflux pump in murine sperm and Pmca4 deletion
      leads to loss of sperm motility and male infertility as there is no compensatory
      upregulation of the remaining Ca2+ pump, PMCA1. Of the four family members of
      PMCAs (PMCA1-4), PMCA1 and PMCA4 are ubiquitous, and to date there have been no
      reports of one isoform being upregulated to compensate for another in any
      organ/tissue. Since Pmca4-/- females are fertile, despite the abundant expression
      of PMCA4 in wild-type (WT) OVS, we propose that OVS serve a role of packaging and
      delivering to sperm elevated levels of PMCA1 in Pmca4-/- during proestrus/estrus
      to compensate for PMCA4's absence. STUDY DESIGN, SIZE, DURATION: Fallopian tubes
      from pre-menopausal women undergoing hysterectomy were used to study EVs in the
      luminal fluid. Oviducts from sexually mature WT mice were sectioned after
      perfusion fixation to detect EVs in situ. Oviducts were recovered from WT and
      Pmca4-/- after hormonally induced estrus and sectioned for PMCA1
      immunofluorescence (IF) (detected with confocal microscopy) and hematoxylin and
      eosin staining. Reproductive tissues, luminal fluids and EVs were recovered after
      induced estrus and after natural cycling for western blot analysis of PMCA1 and
      qRT-PCR of Pmca1 to compare expression levels in WT and Pmca4-/-. OVS,
      uterosomes, and epididymal luminal fluid were included in the comparisons. WT and
      Pmca4-/- OVS were analyzed for the presence of known PMCA4 partners in sperm and
      their ability to interact with PMCA1, via co-immunoprecipitation. In vitro uptake
      of PMCA1 from OVS was analyzed in capacitated and uncapacitated sperm via
      quantitative western blot analysis, IF localization and flow cytometry. Caudal
      sperm were also assayed for uptake of tyrosine-phosphorylated proteins which were
      shown to be present in OVS. Finally, PMCA1 and PMCA4 in OVS and that delivered to
      sperm were assayed for enzymatic activity. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Human fallopian tubes were flushed to recover luminal fluid which was
      processed for OVS via ultracentrifugation. Human OVS were negatively stained for
      transmission electron microscopy (TEM) and subjected to immunogold labeling, to
      detect PMCA4. Western analysis was used to detect HSC70 (an EV biomarker), PMCA1
      and endothelial nitric oxide synthase (eNOS) which is a fertility-modulating
      protein delivered to human sperm by prostasomes. Oviducts of sexually mature
      female mice were sectioned after perfusion fixation for TEM tomography to obtain
      3D information and to distinguish cross-sections of EVs from those of microvilli
      and cilia. Murine tissues, luminal fluids and EVs were assayed for PMCA1 (IF and
      western blot) or qRT-PCR. PMCA1 levels from western blots were quantified, using
      band densities and compared in WT and Pmca4-/- after induced estrus and in
      proestrus/estrus and metestrus/diestrus in cycling females. In vitro uptake of
      PMCA1 and tyrosine-phosphorylated proteins was quantified with flow cytometry
      and/or quantitative western blot. Ca2+-ATPase activity in OVS and sperm before
      and after PMCA1 and PMCA4 uptake was assayed, via the enzymatic hydrolysis rate
      of ATP. MAIN RESULTS AND THE ROLE OF CHANCE: TEM revealed that human oviducts
      contain EVs (exosomal and microvesicular). These EVs contain PMCA4
      (immunolabeling), eNOS and PMCA1 (western blot) in their cargo. TEM tomography
      showed the murine oviduct with EV-containing blebs which typify the apocrine
      pathway for EV biogenesis. Western blots revealed that during proestrus/estrus
      PMCA1 was significantly elevated in the oviductal luminal fluid (OLF) (P = 0.02)
      and in OVS (P = 0.03) of Pmca4-/-, compared to WT. Further, while PMCA1 levels
      did not fluctuate in OLF during the cycle in WT, they were significantly (P =
      0.02) higher in proestrus/estrus than at metestrus/diestrus in Pmca4-/-. The
      elevated levels of PMCA1 in proestrus/estrus, which mimics PMCA4 in WT, is
      OLF/OVS-specific, and is not seen in oviductal tissues, uterosomes or epididymal
      luminal fluid of Pmca4-/-. However, qRT-PCR revealed significantly elevated
      levels of Pmca1 transcript in Pmca4-/- oviductal tissues, compared to WT. PMCA1
      could be transferred from OVS to sperm and the levels were significantly higher
      for capacitated vs uncapacitated sperm, as assessed by flow cytometry (P = 0.001)
      after 3 h co-incubation, quantitative western blot (P < 0.05) and the frequency
      of immuno-labeled sperm (P < 0.001) after 30 min co-incubation. Tyrosine
      phosphorylated proteins were discovered in murine OVS and could be delivered to
      sperm after their co-incubation with OVS, as detected by western,
      immunofluorescence localization, and flow cytometry. PMCA1 and PMCA4 in OVS were
      shown to be enzymatically active and this activity increased in sperm after OVS
      interaction. LARGE SCALE DATA: None. LIMITATIONS REASONS FOR CAUTION: Although
      oviductal tissues of WT and Pmca4-/- showed no significant difference in PMCA1
      levels, Pmca4-/- levels of OVS/OLF during proestrus/estrus were significantly
      higher than in WT. We have attributed this enrichment or upregulation of PMCA1 in
      Pmca4-/- partly to selective packaging in OVS to compensate for the lack of
      PMCA4. However, in the absence of a difference between WT and Pmca4-/- in the
      PMCA1 levels in oviductal tissues as a whole, we cannot rule out significantly
      higher PMCA1 expression in the oviductal epithelium that gives rise to the OVS as
      significantly higher Pmca1 transcripts were detected in Pmca4-/-. WIDER
      IMPLICATIONS OF THE FINDINGS: Since OVS and fertility-modulating cargo components
      are conserved in humans, it suggests that murine OVS role in regulating the
      expression of proteins required for capacitation and fertility is also conserved.
      Secondly, OVS may explain some of the differences in in vivo and in vitro
      fertilization for mouse mutants, as seen in mice lacking the gene for FER which
      is the enzyme required for sperm protein tyrosine phosphorylation. Our
      observation that murine OVS carry and can modulate sperm protein tyrosine
      phosphorylation by delivering them to sperm provides an explanation for the in
      vivo fertility of Fer mutants, not seen in vitro. Finally, our findings have
      implications for infertility treatment and exosome therapeutics. STUDY FUNDING
      AND COMPETING INTEREST(S): The work was supported by National Institute of Health
      (RO3HD073523 and 5P20RR015588) grants to P.A.M.-D. There are no conflicts of
      interests.

PMID- 29370406
TI  - Neuropeptide Y and chronic kidney disease progression: a cohort study.
AB  - Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter that has been
      implicated in various disorders including obesity, gastrointestinal and
      cardiovascular diseases. Methods: We investigated the relationship between
      circulating NPY and the progression of the glomerular filtration rate (GFR) and
      proteinuria and the risk for a combined renal endpoint (>30% GFR loss,
      dialysis/transplantation) in two European chronic kidney disease (CKD) cohorts
      including follow-up of 753 and 576 patients for 36 and 57 months, respectively.
      Results: Average plasma NPY was 104 +/- 32 pmol/L in the first CKD cohort and 119
      +/- 41 pmol/L in the second one. In separate analyses of the two cohorts, NPY
      associated with the progression of the estimated GFR (eGFR) and proteinuria over
      time in both unadjusted and adjusted {eGFR: -3.60 mL/min/1.73 m2 [95% confidence
      interval (CI): -4.46 to - 2.74] P < 0.001 and -0.83 mL/min/1.73 m2 (-1.41 to -
      0.25, P = 0.005); proteinuria: 0.18 g/24 h (0.11-0.25) P < 0.001 and 0.07 g/24 h
      (0.005-0.14) P = 0.033} analyses by the mixed linear model. Accordingly, in a
      combined analysis of the two cohorts accounting for the competitive risk of death
      (Fine and Gray model), NPY predicted (P = 0.005) the renal endpoint [sub
      distribution hazard ratio (SHR): 1.09; 95% CI: 1.03-1.16; P = 0.005] and the SHR
      in the first cohort (1.14, 95% CI: 1.04-1.25) did not differ (P = 0.25) from that
      in the second cohort (1.06, 95% CI: 0.98-1.15). Conclusions: NPY associates with
      proteinuria and faster CKD progression as well as with a higher risk of kidney
      failure. These findings suggest that the sympathetic system and/or properties
      intrinsic to the NPY molecule may play a role in CKD progression.

PMID- 29370407
TI  - Effectiveness of a fully automated internet-based smoking cessation program: a
      randomized controlled trial (STAMP).
AB  - Introduction: The internet offers an interesting alternative to face-to-face and
      telephone-based support for smoking cessation. This study was designed to assess
      the effectiveness of a personalized and automated internet-based program.
      Methods: French current adult smokers willing to quit within 2 weeks were
      recruited for a randomized controlled trial. The intervention consisted of an
      automated program of 45 e-mails ("e-coaching") sent over a 3-month period. The
      control group received a PDF version of a booklet on smoking cessation. Self
      reported 7-day point prevalence smoking abstinence was measured at 6 months
      (primary outcome), at 3 and 12 months of follow-up (secondary outcomes). Results:
      2,478 smokers were randomized (1,242 for e-coaching, 1,236 for the booklet).
      Cessation rate in the intention-to-treat population was not significantly
      different between the two groups at 6 and 12 months, but was higher in the e
      coaching group at 3 months than in the control group (27.5% vs 23.5%, p=0.02,
      OR=1.24, CI=[1.03-1.49]). After adjustment for baseline conditions, the effect of
      the intervention in the per-protocol (PP) sample was significant at 3 months
      (aOR=1.72 [1.31-2.28], p<0.001, N=1042) and at 6 months (aOR=1.27 [1.00-1.60],
      p=0.05, N=1082). GLM repeated measure analyses showed significant group by time
      interaction in the ITT and a significant group effect in the PP population.
      Conclusions: Analyzed intention-to-treat, e-coaching was superior to a booklet at
      3 months (end of intervention) but no more superior at 6 and 12 months follow up.
      Among those who actually followed the program, the effectiveness is also observed
      3 months after the intervention is stopped.

PMID- 29370408
TI  - In vitro activity of the novel antifungal compound F901318 against Australian
      Scedosporium and Lomentospora fungi.
AB  - We determined the in vitro activity of the novel orotomide antifungal, F901318,
      against 30 Lomentospora prolificans, 20 Scedosporium apiospermum, 7 S.
      aurantiacum, and 3 S. boydii, isolates in comparison with standard antifungals.
      Against L. prolificans, F901318 was the most potent compound (MIC90 0.25 MUg/ml);
      the geometric mean MIC (0.26 MUg/ml) was significantly lower (23-80-fold) than
      those of itraconazole, voriconazole, posaconazole, and isavuconazole (all P <
      .001), and amphotericin B (P < .05). F901318 also had good activity against S.
      apiospermum, S. aurantiacum, and S. boydii, comparable to that of voriconazole
      and posaconazole but was more active than isavuconazole for all three species.

PMID- 29370409
TI  - Does the endometrial gene expression of fertile women vary within and between
      cycles?
AB  - STUDY QUESTION: Does gene expression of putative endometrial implantation markers
      vary in expression between menstrual cycles? SUMMARY ANSWER: In fertile women the
      expression of certain genes exhibits a pattern of stable regulation.which is not
      affected even when sampled twice in one cycle. WHAT IS KNOWN ALREADY: Successful
      implantation occurs in a minority of IVF embryo transfers. In contrast to
      knowledge regarding the ovulatory process, there is a sparse understanding of
      endometrial genes critical to implantation. This lack of knowledge hinders
      progress in this field. STUDY DESIGN, SIZE, DURATION: Endometrial pipelle samples
      were collected based on blood endocrinological markers at 2 and 7 days post
      initial LH surge. Five samples were collected over four cycles where the interval
      between collections ranged from sequential months to three years.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Six fertile women attending an IVF
      clinic for male factor infertility, had samples collected. Global gene expression
      profiles were obtained from laser-microdissected, endometrial glands and stroma.
      Nineteen potential proliferation, cytokine and adhesion markers based on previous
      validated reports were studied. MAIN RESULTS AND THE ROLE OF CHANCE: There was a
      significant modification between LH+2 and LH+7 of expression for 23 genes-11 in 8
      in glands and stroma, 4 in stroma only and 3 in glands only suggesting stable,
      controlled regulation. Nevertheless, genes exhibited individual characteristics,
      e.g MKI67 exhibited lower expression at LH+7 than LH+2 and CCL4 higher, whereas
      TRO expressed limited difference in both cell types. Stability between cycles was
      demonstrated for gene expression at both LH+2-more than 60% of genes had <25%
      variation and at LH+7-60% had <30% variation. Further, effects of prior
      collection of an LH+2 sample on gene expression at LH+7 were not detected. The
      range of mRNA expression suggested that a clinical/diagnostic sample at LH+2 and
      LH+7 is likely to be a better index of endometrial function than a single sample.
      The possibility of redundancy suggests a panel would be more informative than a
      single marker. LARGE SCALE DATA: Raw and normalized microarray data have been
      deposited with the EMBL's European Genome-Phenome Archive for collaborative
      analysis, reference ega-box-815 (Lappalainen I, Almeida-King J, Kumanduri V, Senf
      A, Spalding JD, Ur-Rehman S, Saunders G, Kandasamy J, Caccamo M, Leinonen R et
      al. The European Genome-phenome Archive of human data consented for biomedical
      research. Nat Genet 2015;47:692-695.) [https://www.ebi.ac.uk/ega/home].
      LIMITATIONS, REASONS FOR CAUTION: This type of research has difficulties of
      recruitment of fertile women for multiple blood testing and repeat endometrial
      biopsies. Therefore, these data had decreased statistical power due to the
      overall participant numbers. However, the inclusion of four cycles for each
      participant permitted the aim of obtaining information on intercycle and
      intracycle variability to be achieved. WIDER IMPLICATIONS OF THE FINDINGS: Our
      results support the feasibility of a clinical means of identification of a
      functional receptive endometrium. The robustness of data from individual women
      suggests that samples from one cycle can generally be applied to subsequent
      cycles. STUDY FUNDING/COMPETING INTEREST(S): Funding was granted from the
      Tertiary Education Commission of New Zealand, Contract I.D.:UOOX06007. There are
      no competing interests.

PMID- 29370411
TI  - Methodological Concerns about a Systematic Review and Meta-analysis of Maternal
      Active Smoking during Pregnancy and Low Birth Weight.

PMID- 29370413
TI  - Editorial: the 15th annual Nucleic Acids Research Web Server issue 2017.

PMID- 29370410
TI  - Gut Microbial Diversity in Women With Polycystic Ovary Syndrome Correlates With
      Hyperandrogenism.
AB  - Context: A majority of women with polycystic ovary syndrome (PCOS) have metabolic
      abnormalities that result in an increased risk of developing type 2 diabetes and
      heart disease. Correlative studies have shown an association between changes in
      the gut microbiome and metabolic disorders. Two recent studies reported a
      decrease in alpha diversity of the gut microbiome in women with PCOS compared
      with healthy women. Objective: We investigated whether changes in the gut
      microbiome correlated with specific clinical parameters in women with PCOS
      compared with healthy women. We also investigated whether there were changes in
      the gut microbiome in women with polycystic ovarian morphology (PCOM) who lacked
      the other diagnostic criteria of PCOS. Participants: Subjects were recruited at
      the Poznan University of Medical Sciences. Fecal microbial diversity profiles of
      healthy women (n = 48), women with PCOM (n = 42), and women diagnosed with PCOS
      using the Rotterdam criteria (n = 73) were analyzed using 16S ribosomal RNA gene
      sequencing. Results: Lower alpha diversity was observed in women with PCOS
      compared with healthy women. Women with PCOM had a change in alpha diversity that
      was intermediate between that of the other two groups. Regression analyses showed
      that hyperandrogenism, total testosterone, and hirsutism were negatively
      correlated with alpha diversity. Permutational multivariate analysis of variance
      in UniFrac distances showed that hyperandrogenism was also correlated with beta
      diversity. A random forest identified bacteria that discriminated between healthy
      women and women with PCOS. Conclusion: These results suggest that
      hyperandrogenism may play a critical role in altering the gut microbiome in women
      with PCOS.

PMID- 29370412
TI  - Visualizing value for money in public health interventions.
AB  - Background: The Socio-Technical Allocation of Resources (STAR) has been developed
      for value for money analysis of health services through stakeholder workshops.
      This article reports on its application for prioritization of interventions
      within public health programmes. Methods: The STAR tool was used by identifying
      costs and service activity for interventions within commissioned public health
      programmes, with benefits estimated from the literature on economic evaluations
      in terms of costs per Quality-Adjusted Life Years (QALYs); consensus on how these
      QALY values applied to local services was obtained with local commissioners.
      Results: Local cost-effectiveness estimates could be made for some interventions.
      Methodological issues arose from gaps in the evidence base for other
      interventions, inability to closely match some performance monitoring data with
      interventions, and disparate time horizons of published QALY data. Practical
      adjustment for these issues included using population prevalences and utility
      states where intervention specific evidence was lacking, and subdivision of large
      contracts into specific intervention costs using staffing ratios. The STAR
      approach proved useful in informing commissioning decisions and understanding the
      relative value of local public health interventions. Conclusions: Further work is
      needed to improve robustness of the process and develop a visualization tool for
      use by public health departments.

PMID- 29370414
TI  - Robotic right middle lobectomy with a subxiphoid utility port.
AB  - We present the case of a 74-year-old man with Stage IIa pulmonary adenocarcinoma,
      for which he underwent a robotic right middle lobectomy. A 4-armed, 5-port
      approach was used. Four intercostal ports were created above the ninth rib using
      the Cerfolio's technique. The subxiphoid port was created in the midline, 5 cm
      down from the xiphisternum. The robot offers higher image quality, depth
      perception and improved articulation of the instruments, allowing for more
      accurate dissection and stitching. The usage of a subxiphoid utility port reduces
      the clashing between instruments, offers a good angle for stapling and provides a
      direct view of the instruments entering into the chest. Specimen removal through
      the subxiphoid port may reduce postoperative pain and enhance patient recovery.
      The use of the subxiphoid approach as a utility port for robotic surgery is
      promising and may be a suitable replacement for the traditional utility port.

PMID- 29370415
TI  - Applying host disease status biomarkers to therapeutic response monitoring in
      invasive aspergillosis patients.
AB  - One critical factor impeding successful management of invasive aspergillosis (IA)
      is the lack of reliable biomarkers to assess therapeutic response. We
      hypothesized that changes in certain host biomarkers reflect the nature of
      infection status and disease progression. Upon primary IA diagnosis, these
      disease status biomarkers can be monitored to track response to antifungal
      therapy and provide early markers that prognosticate likelihood of response.
      Herein, we analyzed serum levels of three prominent host disease status
      biomarkers C-reactive protein (CRP), haptoglobin (Hp), and annexin A1 (ANXA1) in
      IA patients during antifungal therapy. A total of 81 serial serum samples were
      collected at five or six different time points relative to IA diagnosis from 15
      probable IA patients (10 acute leukemia [AL] and five hematopoietic stem cell
      transplantation [HSCT]). Of note, different biomarker profiles were observed in
      AL and HSCT patients, as not only levels of markers were significantly lower in
      HSCT patients but also more prominent interconnections among markers were
      observed in AL patients. Using a composite evaluation, patients were categorized
      as responders, nonresponders, and stable cases at last specimen. For AL
      responders, typical biomarker profiles were high initially but rapidly decreased
      for CRP and Hp post antifungal therapy, while low initial ANXA1 values were
      restored to normal levels after treatment. In contrast, CRP and Hp were
      persistently elevated whilst ANXA1 remained low throughout therapy in AL non
      responders. As a pilot proof-of-concept study, our work demonstrates the great
      potential of using host biomarkers to monitor early therapeutic response in
      leukemia patients.

PMID- 29370417
TI  - Slaughter performance and meat quality of Milanino chickens reared according to a
      specific free-range program.
AB  - The study aimed to characterize meat quality traits of Milanino chickens reared
      according to a specific free-range farming program. A total of 120 birds was
      reared straight-run in outdoor pens (8 m2/bird) from 35 d of life and fed ad
      libitum a low (16%) protein diet. At 180 d of age, 20 birds (10 birds/sex) were
      slaughtered, and carcass weight data were recorded. After processing, carcasses
      were refrigerated at 4 degrees C for 24 hours. Then, the right breast and thigh
      with skin were collected and color parameters, pH, water-holding capacity (WHC),
      and chemical composition were determined. The left breast and thigh were stored
      at -20 degrees C until cooking loss and tenderness evaluation. Milanino was
      confirmed to be a heavy breed with a sexual dimorphism in relation to adult body
      weight. A high general carcass yield was recorded. Milanino meat was
      characterized by high protein and low fat contents compared with the standard
      broiler meat. Differences in meat composition were recorded according to the sex:
      females presented higher values of dry matter (breast and thigh), protein
      (breast), and fat (breast and thigh) contents. The meat with skin presented an
      intense luminosity, and this trait was higher in the females. The muscle color
      was characterized by high redness and yellowness indices with differences
      according to the sex: Higher yellowness index was observed in female carcasses,
      while higher redness index was detected in male breast samples. The pH muscle
      values were similar to those reported in other autochthonous breeds. WHC values
      did not show variation between sexes. In contrast, cooking loss values recorded
      in thigh samples were lower in males compared to females. The degree of
      tenderness of Milanino meat was not affected by the sex. However, the potential
      loss of water and the toughness in Milanino meat were low compared to other local
      chicken breed meat. The present results support the breeding of Milanino chickens
      for meat production according to its specific straight-run free-range system.

PMID- 29370416
TI  - Plant-pathogen interactions: leaf physiology alterations in poplars infected with
      rust (Melampsora medusae).
AB  - Rust produced by Melampsora sp. is considered one of the most relevant diseases
      in poplar plantations. Growth reduction in poplar plantations takes place because
      rust, like other pathogens, alters leaf physiology. There is not a complete
      evaluation of several of the physiological traits that can be affected by rust at
      leaf level. Therefore, the aim of this work was to evaluate, in an integrative
      way and in the same pathosystem, which physiological processes are affected when
      Populus deltoides Bartr. ex Marsh. leaves are infected by rust (Melampsora
      medusae Thumen). Leaves of two clones with different susceptibility to rust were
      analyzed. Field and pot experiments were performed, and several physiological
      traits were measured in healthy and infected leaves. We conclude that rust
      affects leaf mesophyll integrity, and so water movement in the leaf in liquid
      phase is affected. As a consequence, gas exchange is reduced, affecting both
      carbon fixation and transpiration. However, there is an increase in respiration
      rate, probably due to plant and fungal respiration. The increase in respiration
      rate is important in the reduction of net photosynthetic rate, but also some
      damage in the photosynthetic apparatus limits leaf capacity to fix carbon. The
      decrease in chlorophyll content would start later and seems not to explain the
      reduction in net photosynthetic rate. Both clones, although they have different
      susceptibility to rust, are affected in the same physiological mechanisms.

PMID- 29370418
TI  - The Future Burden of Colorectal Cancer Among US Blacks and Whites.
AB  - Although overall colorectal cancer (CRC) incidence rates in the United States are
      declining, rates among younger persons (age < 55 years) are increasing,
      particularly among US whites. We assessed how these trends will impact the future
      burden (up to 2040) of CRC among US blacks and whites using an age-period-cohort
      model. Over the last four decades (1973 to 2014), CRC incidence rates for all
      ages (both sexes) have dropped by 6.6% and 33.9% in US blacks and whites,
      respectively. Yet we predict an upward turn in CRC cancer incidence rates over
      the next quarter century, particularly among US whites. The age-standardized
      rates of CRC were 55.4 and 43.2 per 100 000 among US blacks and whites in 2014,
      respectively, and are projected to be 49.5 and 43.1 in 2040, respectively. Future
      interventions are needed to reduce the striking differences in CRC incidence
      between blacks and whites.

PMID- 29370419
TI  - Study of the role of the covalently linked cell wall protein (Ccw14p) and yeast
      glycoprotein (Ygp1p) within biofilm formation in a flor yeast strain.
AB  - Flor yeasts are Saccharomyces cerevisiae strains noted by their ability to create
      a type of biofilm in the air-liquid interface of some wines, known as 'flor' or
      'velum', for which certain proteins play an essential role. Following a proteomic
      study of a flor yeast strain, we deleted the CCW14 (covalently linked cell wall
      protein) and YGP1 (yeast glycoprotein) genes-codifying for two cell surface
      glycoproteins-in a haploid flor yeast strain and we reported that both influence
      the weight of the biofilm as well as cell adherence (CCW14).

PMID- 29370420
TI  - C3 glomerulonephritis secondary to mutations in factors H and I: rapid recurrence
      in deceased donor kidney transplant effectively treated with eculizumab.
AB  - Background: C3 glomerulonephritis (C3GN) is caused by alternate complement
      pathway over-activation. It frequently progresses to end-stage renal disease,
      recurs in two-thirds of transplants and in half of these cases progresses to
      allograft loss. There is currently no proven treatment for C3GN. Case
      Presentation: We describe a family segregating pathogenic alleles of complement
      factor H and I (CFH and CFI). The only member carrying both mutations developed
      C3GN. Prolonged delayed graft function after deceased donor transplantation,
      heavy proteinuria and isolated C3 hypocomplementemia prompted an allograft biopsy
      confirming diagnosis of recurrent C3GN. Discussion: This is the first report of
      early recurrence of C3GN in an allograft in a patient with known mutations in
      complement regulatory genes and no preexisting para-proteinemia. Complement
      activation resulting from ischemia-reperfusion injury from prolonged cold
      ischemia time unabated in the setting of deficiency of two major complement
      regulators likely led to the early and severe recurrence. In atypical hemolytic
      uremic syndrome, the terminal complement cascade activation in the sentinel event
      initiating endothelial injury; blockade at the level of C5 convertase with
      eculizumab is uniformly highly effective in management. C3 glomerulopathies (C3GN
      and dense deposit disease) are a more complex and heterogeneous group. The
      relative degree of dysregulation at the levels of C3 and C5 convertases and
      therefore response to eculizumab varies among patients. In our patient, the
      clinical response to eculizumab was dramatic with recovery of allograft function
      and complete resolution of proteinuria. We review all cases of recurrent C3
      glomerulopathy treated with eculizumab and discuss how complement biomarkers may
      aid in predicting response to therapy.

PMID- 29370421
TI  - Examining the sustainability potential of a multisite pilot to integrate alcohol
      screening and brief intervention within three primary care systems.
AB  - The U.S. Preventive Services Task Force recommends that clinicians adopt
      universal alcohol screening and brief intervention as a routine preventive
      service for adults, and efforts are underway to support its widespread
      dissemination. The likelihood that healthcare systems will sustain this change,
      once implemented, is under-reported in the literature. This article identifies
      factors that were important to postimplementation sustainability of an evidence
      based practice change to address alcohol misuse that was piloted within three
      diverse primary care organizations. The Centers for Disease Control and
      Prevention funded three academic teams to pilot and evaluate implementation of
      alcohol screening and brief intervention within multiclinic healthcare systems in
      their respective regions. Following the completion of the pilots, teams used the
      Program Sustainability Assessment Tool to retrospectively describe and compare
      differences across eight sustainability domains, identify strengths and potential
      threats to sustainability, and make recommendations for improvement. Health
      systems varied across all domains, with greatest differences noted for Program
      Evaluation, Strategic Planning, and Funding Stability. Lack of funding to sustain
      practice change, or data monitoring to promote fit and fidelity, was an
      indication of diminished Organizational Capacity in systems that discontinued the
      service after the pilot. Early assessment of sustainability factors may identify
      potential threats that could be addressed prior to, or during implementation to
      enhance Organizational Capacity. Although this study provides a retrospective
      assessment conducted by external academic teams, it identifies factors that may
      be relevant for translating evidence-based behavioral interventions in a way that
      assures that they are sustained within healthcare systems.

PMID- 29370422
TI  - Two Novel MicroRNA Biomarkers Related to beta-Cell Damage and Their Potential
      Values for Early Diagnosis of Type 1 Diabetes.
AB  - Context: New strategies and biomarkers are needed in the early detection of beta
      cell damage in the progress of type 1 diabetes mellitus (T1DM). Objective: To
      explore whether serum microRNAs (miRNA) should be served as biomarkers for T1DM.
      Design, Settings, and Patients: The miRNA profile was established with miRNA
      microarray in discovery phase (six T1DM, six controls). A miRNA-based model for
      T1DM diagnosis was developed using logistic regression analysis in the training
      dataset (40 T1DM, 56 controls) and then validated with leave-one-out cross
      validation and another independent validation dataset (33 T1DM, 29 controls).
      Main Outcome Measures: Quantitative reverse transcription polymerase chain
      reaction was applied to confirm the differences of candidate miRNAs between T1DM
      and controls. Area under the receiver-operating characteristic (ROC) curve (AUC)
      was used to evaluate diagnostic accuracy. INS-1 cells, streptozotocin-treated
      mice (n = 4), and nonobese diabetic (NOD) mice (n = 12) were used to evaluate the
      association of miRNAs with beta-cell damage. Results: A miRNA -based model was
      established in the training dataset with high diagnostic accuracy for T1DM (AUC =
      0.817) based on six candidate differential expressed miRNAs identified in
      discovery phase. The validation dataset showed the model's satisfactory
      diagnostic performance (AUC = 0.804). Secretions of miR-1225-5p and miR-320c were
      significantly increased in streptozotocin-treated mice and INS-1 cells.
      Noteworthy, the elevation of these two miRNAs was observed before glucose
      elevation in the progress of diabetes in NOD mice. Conclusions: Two miRNA
      biomarkers (miR-1225-5p and miR-320c) related to beta-cell damage were identified
      in patients with recent-onset T1DM. The miRNA-based model established in this
      study exhibited a good performance in diagnosis of T1DM.

PMID- 29370423
TI  - Excitation of long-wavelength surface optical vibrational modes in films, cubes
      and film/cube composite system using an atom-sized electron beam.
AB  - Using spatially resolved Electron Energy-Loss Spectroscopy, we investigate the
      excitation of long-wavelength surface optical vibrational modes in elementary
      types of nanostructures: an amorphous SiO2 slab, an MgO cube, and in the
      composite cube/slab system. We find rich sets of optical vibrational modes
      strongly constrained by the nanoscale size and geometry. For slabs, we find two
      surface resonances resulting from the excitation of surface phonon polariton
      modes. For cubes, we obtain three main highly localized corner, edge, and face
      resonances. The response of those surface phonon resonances can be described in
      terms of eigenmodes of the cube and we show that the corresponding mode pattern
      is recovered in the spatially resolved EELS maps. For the composite
      cube/substrate system we find that interactions between the two basic structures
      are weak, producing minor spectral shifts and intensity variations (transparency
      behaviour), particularly for the MgO-derived modes.

PMID- 29370424
TI  - Effects of the sodium-glucose co-transporter 2 inhibitor dapagliflozin in
      patients with type 2 diabetes and Stages 3b-4 chronic kidney disease.
AB  - Background: The sodium-glucose co-transporter 2 inhibitor dapagliflozin decreases
      haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary
      albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy
      and safety of this drug have not been properly defined in patients with type 2
      diabetes and Stages 3b-4 chronic kidney disease (CKD). Methods: In a pooled
      analysis of 11 phase 3 randomized controlled clinical trials, we determined least
      square mean changes in HbA1c, body weight, BP, estimated glomerular filtration
      rate (eGFR) and UACR over 102 weeks in patients with type 2 diabetes and an eGFR
      between 12 to less than 45 mL/min/1.73 m2 receiving placebo (n = 69) or
      dapagliflozin 5 or 10 mg (n = 151). Effects on UACR were determined in a subgroup
      of patients with baseline UACR >=30 mg/g (n = 136). Results: Placebo-corrected
      changes in HbA1c with dapagliflozin 5 and 10 mg were 0.03% [95% confidence
      interval (CI) -0.3-0.3] and 0.03% (95% CI -0.2-0.3) during the overall 102-week
      period. Dapagliflozin 5 and 10 mg compared with placebo reduced UACR by - 47.1%
      (95% CI -64.8 to - 20.6) and -38.4% (95% CI -57.6 to - 10.3), respectively.
      Additionally, dapagliflozin 5 and 10 mg compared with placebo reduced BP and body
      weight. eGFR increased with placebo during the first 4 weeks but did not change
      with dapagliflozin. There were no between-group differences in eGFR at the end of
      follow-up. Adverse events associated with renal function occurred more frequently
      in the dapagliflozin 10-mg group. These events were mainly asymptomatic increases
      in serum creatinine. Conclusions: Dapagliflozin did not decrease HbA1c in
      patients with type 2 diabetes and Stages 3b-4 CKD, but decreased UACR, BP and
      body weight to a clinically meaningful extent. These results support a large
      outcome trial in this population to confirm long-term safety and efficacy in
      reducing adverse clinical endpoints.

PMID- 29370425
TI  - Meaningful use's benefits and burdens for US family physicians.
AB  - Objective: The federal meaningful use (MU) program was aimed at improving
      adoption and use of electronic health records, but practicing physicians have
      criticized it. This study was aimed at quantifying the benefits (ie, usefulness)
      and burdens (ie, workload) of the MU program for practicing family physicians.
      Materials and Methods: An interdisciplinary national panel of experts (physicians
      and engineers) identified the work associated with MU criteria during patient
      encounters. They conducted a national survey to assess each criterion's level of
      patient benefit and compliance burden. Results: In 2015, 480 US family physicians
      responded to the survey. Their demographics were comparable to US norms. Eighteen
      of 31 MU criteria were perceived as useful for more than half of patient
      encounters, with 13 of those being useful for more than two-thirds. Thirteen
      criteria were useful for less than half of patient encounters. Four useful
      criteria were reported as having a high compliance burden. Discussion: There was
      high variability in physicians' perceived benefits and burdens of MU criteria. MU
      Stage 1 criteria, which are more related to basic/routine care, were perceived as
      beneficial by most physicians. Stage 2 criteria, which are more related to
      complex and population care, were perceived as less beneficial and more
      burdensome to comply with. Conclusion: MU was discontinued, but the merit-based
      incentive payment system within the Medicare Access and CHIP Reauthorization Act
      of 2015 adopted its criteria. For many physicians, MU created a significant
      practice burden without clear benefits to patient care. This study suggests that
      policymakers should not assess MU in aggregate, but as individual criteria for
      open discussion.

PMID- 29370426
TI  - Identifying At-Risk Subgroups for Acute Postsurgical Pain: A Classification Tree
      Analysis.
AB  - Objective: Acute postsurgical pain is common and has potentially negative long
      term consequences for patients. In this study, we evaluated effects of presurgery
      sociodemographics, pain experiences, psychological influences, and surgery
      related variables on acute postsurgical pain using logistic regression vs
      classification tree analysis (CTA). Design: The study design was prospective.
      Setting: This study was carried out at Chongqing No. 9 hospital, Chongqing,
      China. Subjects: Patients (175 women, 84 men) completed a self-report battery 24
      hours before surgery (T1) and pain intensity ratings 48-72 hours after surgery
      (T2). Results: An initial logistic regression analysis identified pain self
      efficacy as the only presurgery predictor of postoperative pain intensity.
      Subsequently, a classification tree analysis (CTA) indicated that lower vs higher
      acute postoperative pain intensity levels were predicted not only by pain self
      efficacy but also by its interaction with disease onset, pain catastrophizing,
      and body mass index. CTA results were replicated within a revised logistic
      regression model. Conclusions: Together, these findings underscored the potential
      utility of CTA as a means of identifying patient subgroups with higher and lower
      risk for severe acute postoperative pain based on interacting characteristics.

PMID- 29370427
TI  - ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer.
AB  - Background: ALK, ROS1, and NTRK fusions occur in 0.2% to 2.4% of colorectal
      cancers. Pioneer cases of metastatic colorectal cancer (mCRC) patients bearing
      rearrangements who benefited from anti-ALK, ROS, and TrkA-B-C therapies have been
      reported previously. Here we aimed at characterizing the clinical and molecular
      landscape of ALK, ROS1, and NTRK rearranged mCRC. Methods: Clinical features and
      molecular characteristics of 27 mCRC patients bearing ALK, ROS1, and NTRK
      rearranged tumors were compared with those of a cohort of 319 patients not
      bearing rearrangements by means of Fisher's exact, chi2 test, or Mann-Whitney
      test as appropriate. Overall survival curves were estimated with the Kaplan-Meier
      method and compared using the log-rank test. A Cox proportional hazard model was
      adopted in the multivariable analysis. Deep molecular and immunophenotypic
      characterizations of rearranged cases, including those described in The Cancer
      Genome Atlas database, were performed. All statistical tests were two-sided.
      Results: Closely recalling the "BRAF history," ALK, ROS1, and NTRK rearrangements
      more frequently occurred in elderly patients (P = .02) with right-sided tumors (P
      < .001) and node-spreading (P = .03), RAS wild-type (P < .001), and MSI-high (P <
      .001) cancers. All patients bearing ALK, ROS1, and NTRK fusions had shorter
      overall survival (15.6 months, 95% confidence interval [CI] = 0.0 to 20.4 months)
      than negative patients (33.7 months, 95% CI = 28.3 to 42.1 months), both in the
      univariate (hazard ratio [HR] = 2.17, 95% CI = 1.03 to 4.57, P < .001) and
      multivariable models (HR = 2.33, 95% CI = 1.10 to 4.95, P = .02). All four
      evaluable patients with rearrangements showed primary resistance to anti
      epidermal growth factor receptor agents. Frequent association with potentially
      targetable RNF43 mutations was observed in MSI-high rearranged tumors.
      Conclusions: ALK, ROS1, and NTRK rearrangements define a new rare subtype of mCRC
      with extremely poor prognosis. Primary tumor site, MSI-high, and RAS and BRAF
      wild-type status may help to identify patients bearing these alterations. While
      sensitivity to available treatments is limited, targeted strategies inhibiting
      ALK, ROS, and TrkA-B-C provided encouraging results.

PMID- 29370428
TI  - The effect of high-volume online haemodiafiltration on nutritional status and
      body composition: the ProtEin Stores prEservaTion (PESET) study.
AB  - Background: Compared with conventional haemodialysis (HD), online
      haemodiafiltration (OL-HDF) achieves a more efficient removal of uraemic toxins
      and reduces inflammation, which could favourably affect nutritional status. We
      evaluate the effect of OL-HDF on body composition and nutritional status in
      prevalent high-flux HD (HF-HD) patients. Methods: In all, 33 adults with chronic
      kidney disease (CKD) Stage 5 undergoing maintenance HF-HD were assigned to post
      dilution OL-HDF (n = 17) or to remain on HF-HD (n = 16, control group) for 12
      months. The primary outcome was the change in lean tissue mass (LTM),
      intracellular water (ICW) and body cell mass (BCM) assessed by multifrequency
      bioimpedance spectroscopy (BIS) at baseline and 4, 8 and 12 months. The rate of
      change in these parameters was estimated with linear mixed-effects models.
      Results: Compared with OL-HDF, patients assigned to HF-HD experienced a gradual
      reduction in LTM, ICW and BCM. These differences reached statistical significance
      at Month 12, with a relative difference of 7.31 kg [95% confidence interval (CI)
      2.50-12.11; P = 0.003], 2.32 L (95% CI 0.63-4.01; P = 0.008) and 5.20 kg (95% CI
      1.74-8.66; P = 0.004) for LTM, ICW and BCM, respectively. The normalized protein
      appearance increased in the OL-HDF group compared with the HF-HD group [0.26
      g/kg/day (95% CI 0.05-0.47); P = 0.002], with a relative reduction in high
      sensitive C-reactive protein [-13.31 mg/dL (95% CI -24.63 to -1.98); P = 0.02] at
      Month 12. Conclusions: OL-HDF for 1 year compared with HF-HD preserved muscle
      mass, increased protein intake and reduced the inflammatory state related to
      uraemia and dialysis, supporting the hypothesis that high convection volume can
      benefit nutritional status and prevent protein-energy wasting in HD patients.

PMID- 29370429
TI  - Genetic parameters of feed efficiency traits and their relationships with egg
      quality traits in laying period of ducks.
AB  - The objective of this study was to estimate genetic parameters for feed
      efficiency and relevant traits in 2 laying duck breeds, and to determine the
      relationship of residual feed intake (RFI) with feed efficiency and egg quality
      traits. Phenotypic records on 3,000 female laying ducks (1,500 Shaoxing ducks and
      1,500 Jinyun ducks) from a random mating population were used to estimate genetic
      parameters for RFI, feed conversion ratio (FCR), feed intake (FI), BW, BW gain
      (BWG), and egg mass laid (EML) at 42 to 46 wk of age. The heritability estimates
      for EML, FCR, FI, and RFI were 0.22, 0.19, 0.22, and 0.27 in Shaoxing ducks and
      0.14, 0.19, 0.24, and 0.24 for Jinyun ducks, respectively. RFI showed high and
      positive genetic correlations with FCR (0.47 in Shaoxing ducks and 0.63 in Jinyun
      ducks) and FI (0.79 in Shaoxing ducks and 0.86 in Jinyun ducks). No correlations
      were found in RFI with BW, BWG, or EML at either genetic or phenotypic level. FCR
      was strongly and negatively correlated with EML (-0.81 and -0.68) but
      inconsistently correlated with FI (0.02 and 0.17), suggesting that EML was the
      main influence on FCR. In addition, no significant differences were found between
      low RFI (LRFI) and high RFI (HRFI) ducks in egg shape index, shell thickness,
      shell strength, yolk color, albumen height, or Haugh unit (HU). The results
      indicate that selection for LRFI could improve feed efficiency and reduce FI
      without significant changes in EML or egg quality.

PMID- 29370430
TI  - Social relationships and their impact on health-related outcomes in peritoneal
      versus haemodialysis patients: a prospective cohort study.
AB  - Background: Social relationships are important determinants of health-related
      outcomes for patients with chronic conditions. However, the effects of social
      networks and social support on health outcomes of dialysis patients in different
      treatment modalities have been under studied. Methods: We surveyed peritoneal
      dialysis (PD) and haemodialysis (HD) patients in the Choice of Renal Replacement
      Therapy project about their social relationships and health-care outcomes at
      baseline and 1-year follow-up. Two propensity score-matched groups (n = 353; HD =
      200, PD = 153) with similar age, comorbidity level, education and employment
      status were compared. We used an ego-centred Network Generator to assess
      quantitative and qualitative aspects of social networks and the Berlin Social
      Support Scales to evaluate dimensions of social support, and analysed the effects
      of the social variables on anxiety, depression, autonomy preferences, and
      physical and psychological quality of life. Results: Over time, the non-family
      networks (e.g. friends) of both groups decreased (P = 0.04) and the absolute
      number of types of relationships increased (P = 0.01). The family-network size,
      quality of relationships and social support remained stable. Larger social
      networks were associated with higher participation-seeking preferences (B = 1.39,
      P = 0.002) and lower anxiety (B = -0.11, P = 0.03). Closer and more satisfying
      relationships were associated with better psychological well-being (B = 3.41, P =
      0.003). PD patients had larger networks, more types of relationships and received
      more social support than HD patients (P <= 0.05). Conclusions: These differences
      may reflect the degree of autonomy and self-care associated with the different
      treatment modalities. In practice, our findings suggest that the early
      identification and inclusion of persons providing social support for patients may
      have a positive effect on different aspects of their care and quality of life.

PMID- 29370431
TI  - Evidence from qualitative studies of youth about the impacts of tobacco control
      policy on young people in Europe: a systematic review.
AB  - Introduction: A range of tobacco control policies endeavour to prevent smoking
      uptake in young people, yet relatively little is known about how such
      interventions impact young people's engagement with smoking. We reviewed existing
      qualitative evidence on young people and smoking in Europe in order to assess
      whether, in what ways and why young people comply with, adapt to, resist or
      circumvent tobacco control policies in their respective countries. Methods: We
      undertook a systematic review of academic literature presenting qualitative
      research from Europe on smoking and young people (11-18 years), published from
      2000 - 2015. Bibliographic searches (PubMed, PsycInfo, SSCI) produced 1357
      records, from which 43 relevant papers were assessed for quality and 39 included
      in the review. Results: Most studies were from the UK (27), with a small number
      (one or two each) from other European countries (Denmark, Sweden, Switzerland,
      Belgium, Cyprus, Greece, Hungary, Ireland and Spain). Only 16 articles (11 from
      UK) provided any evidence about the impacts of tobacco control policies on young
      people's smoking. These focussed on smoke-free legislation (four), age of sale
      laws (four), plain packaging (three), and black market tobacco (one).
      Conclusions: There is very little qualitative evidence exploring the impacts of
      tobacco control on youth smoking in Europe. To develop more effective smoking
      prevention policies that take account of local political, social and cultural
      contexts, more qualitative research from a wider range of European countries is
      needed in order to understand how tobacco control impacts on young people's
      social worlds and smoking behaviours. Implications: Smoking is the leading cause
      of premature mortality in Europe. However, there is little qualitative evidence
      exploring the impact of tobacco control policies on young people in Europe. Most
      comes from the UK and focuses on a narrow range of policies. Thus we have a
      limited understanding of how and in what ways tobacco control policies reach
      young people, their engagement with these, and how local context affects their
      impact. More qualitative research is needed, from a wider range of countries and
      on a broader range of tobacco control policies, in order to strengthen the
      evidence-base for reducing youth smoking.

PMID- 29370432
TI  - Comparative phenology of dormant Japanese pear (Pyrus pyrifolia) flower buds: a
      possible cause of 'flowering disorder'.
AB  - Mild winters influenced by global warming have increased the incidence of erratic
      flowering ('flowering disorder') in Japanese pear (Pyrus pyrifolia Nakai) trees
      in Japan. To discover how, when and what kind of disorder/damage occur in pear
      flower buds, we observed axillary flower buds of two cultivars, 'Kosui' (a mid
      chill cultivar) and 'Niitaka' (a high-chill cultivar), grown at five locations.
      We focused on the phenology from autumn 2015 to spring 2016, when temperatures
      were higher than for average years, especially from September to January, and
      large fluctuations occurred due to El Nino. During the blooming season in the
      spring of 2016, both the percentage of blooming flower buds and the number of
      florets per flower bud decreased in trees located at lower latitudes (with lower
      chilling accumulation) with a more severe problem in 'Niitaka' than in 'Kosui'.
      As shown by forcing excised shoots, the onset and release of endodormancy
      occurred earlier in 'Kosui' than 'Niitaka' and occurred earlier in trees growing
      at higher latitudes than at lower latitudes (warmer regions). The freezing
      tolerance of flower buds, measured as the lethal temperature for 50% survival
      (LT50), was similar for the cultivars beginning in autumn and reached maximum
      levels, LT50 values of less than -12  degrees C, between late-December and mid
      January in both cultivars, except for those in Kagoshima (the lowest latitude),
      where the maximum LT50 was only -5  degrees C throughout the season. We propose
      that warmer autumn-winter temperatures may prevent the acquisition of freezing
      tolerance, disturb endodormancy progression and disrupt floral organ development,
      thereby causing flowering disorder in pear trees. The risk of occurrence of
      flowering disorder in pear may be higher in high-chill cultivars than in low- or
      mid-chill cultivars and at lower latitudes compared with higher latitudes.

PMID- 29370433
TI  - Integrating and coordinating care between the Women, Infants, and Children
      Program and pediatricians to improve patient-centered preventive care for healthy
      growth.
AB  - New care delivery models call for integrating health services to coordinate care
      and improve patient-centeredness. Such models have been embraced to coordinate
      care with evidence-based strategies to prevent obesity. Both the Special
      Supplemental Program for Women, Infants and Children (WIC) Program and
      pediatricians are considered credible sources of preventive guidance, and
      coordinating these independent siloes would benefit a vulnerable population.
      Using semistructured focus groups and interviews, we evaluated practices,
      messaging, and the prospect of integrating and coordinating care. Across
      Pennsylvania, WIC nutritionists (n = 35), pediatricians (n = 15), and parents (N
      = 28) of an infant or toddler participated in 2016. Three themes were identified:
      health assessment data sharing (e.g., iron, growth measures), benefits and
      barriers to integrated health services, and coordinating care to reduce
      conflicting educational messages (e.g., breastfeeding, juice, introduction of
      solids). Stakeholders supported sharing health assessment data and integrating
      health services as strategies to enhance the quality of care, but were concerned
      about security and confidentiality. Overall, integrated, coordinated care was
      perceived to be an acceptable strategy to facilitate consistent, preventive
      education and improve patient-centeredness.

PMID- 29370434
TI  - Chlorophyll Fluorescence and Reflectance-Based Non-Invasive Quantification of
      Blast, Bacterial Blight and Drought Stresses in Rice.
AB  - Response of rice (Oryza sativa) exposed to both biotic and abiotic stresses can
      be quantified by employing fast and accurate optical methods. In this study, the
      overall stress responses of (i) 12 near-isogenic lines (NILs) in the genetic
      background of the rice blast-susceptible cultivar Lijiangxintuanheigu (LTH) and
      (ii) four NILs in the genetic background of the bacterial blight-susceptible
      cultivar IR24, were inspected by means of Chl fluorescence (Chl-F) imaging. The
      distribution of the maximum and effective quantum yield of PSII (Fv/FM and QY)
      and steady-state Chl-F (Ft) were found to be effective in differentiating
      symptomatic leaf tissue for both rice blast and bacterial blight, which
      correlated well with 30 cycles of rice blast and six cycles of bacterial blight
      previously screened using classical (manual) approaches. Subsequently, identified
      Chl-F parameters allowing detection under ambient light (QY and Ft) were tested
      across both biotic and abiotic (drought) stress experiments, for rice cultivars
      contrasting for drought stress response (N22, IR64 and NSIC Rc 222). Their
      applicability has been proven for both rice blast and bacterial blight; however,
      QY failed to detect the effect of drought. In addition to Chl-F, the usefulness
      of 11 selected vegetation indices (Vis) was tested on these three cultivars
      exposed to particular stresses: (i) rice blast was detectable by Vis calculated
      from the visible spectrum; (ii) bacterial blight by near-infrared-related Vis;
      and (iii) drought by Vis calculated from the visible spectrum. The key Chl-F
      parameters and/or Vis have been summarized and discussed.

PMID- 29370435
TI  - Engineered cysteine antibodies: an improved antibody-drug conjugate platform with
      a novel mechanism of drug-linker stability.
AB  - Antibody-drug conjugates (ADCs) are fulfilling the promise of targeted therapy
      with meaningful clinical success. An intense research effort is directed towards
      improving pharmacokinetic profiles, toxicity and chemical stability of ADCs. The
      majority of ADCs use amide and thioether chemistry to link potent cytotoxic
      agents to antibodies via endogenous lysine and cysteine residues. While maleimide
      cysteine conjugation is used for many clinical stage ADC programs, maleimides
      have been shown to exhibit some degree of post-conjugation instability. Previous
      research with site-directed mutagenic incorporation of cysteine residues for
      conjugation revealed that the stability of the drug-antibody linkage depends on
      the site of conjugation. Here we report on a collection of engineered cysteine
      antibodies (S239C, E269C, K326C and A327C) that can be site-specifically
      conjugated to potent cytotoxic agents to produce homogenous 2-loaded ADCs. These
      ADCs confirm that site of conjugation impacts maleimide stability and present a
      novel mechanism of thioether stabilization, effectively unlinking stability from
      either local chemical environment or calculated solvent accessibility and
      expanding the current paradigm for ADC drug-linker stability. These ADCs show
      potent in vitro and in vivo activity while delivering half of the molar
      equivalent dose of drug per antibody when compared to an average 4-loaded ADC. In
      addition, our lead engineered site shields highly hydrophobic drugs, enabling
      conjugation, formulation and clinical use of otherwise intractable chemotypes.

PMID- 29370436
TI  - Predictors of Placebo Response in Pharmacological Clinical Trials of Negative
      Symptoms in Schizophrenia: A Meta-regression Analysis.
AB  - We conducted a meta-regression analysis of all double-blind, randomized, placebo
      controlled clinical trials (DBRCTs) reporting effects of drug and placebo on
      negative symptoms in people with stable schizophrenia and predominant or
      prominent negative symptoms to assess predictors of placebo response in these
      individuals. We used Preferred Reporting Items for Systematic Reviews and Meta
      analyses (PRISMA) guidelines for systematic reviews and meta-analyses to conduct
      a systematic literature search to identify DBRCTs assessing treatment efficacy on
      negative symptoms, as primary outcome, in patients with stable schizophrenia and
      predominant or prominent negative symptoms. We used Cohen's d, with 95% CIs, as
      the effect size measure for placebo response, based on negative symptom change
      scores from baseline to endpoint (range 4 to 24 wk) in the placebo-treated group.
      We included 18 DBRCTs from 17 publications, assessing the effect of 13 drugs vs
      placebo on negative symptoms and comprising 998 patients, in the meta-regression
      analyses. Overall, drugs showed greater efficacy than placebo in reducing
      negative symptoms, with small effect size (Cohen's d: 0.208, P = .020). Placebo
      response was significant (P < .001) and clinically relevant (Cohen's d: 2.909),
      but there was significant heterogeneity and high risk of publication bias.
      Multivariable meta-regression analyses showed that larger numbers of arms in the
      trial, larger numbers of study sites and industry sponsorship were significant
      moderators of placebo response in this population. Our results suggest that some
      clinical trial design and operational factors affect the level of placebo
      response in such studies, thus highlighting the need for designs better suited to
      assess these outcomes.

PMID- 29370437
TI  - Short linear motif core and flanking regions modulate retinoblastoma protein
      binding affinity and specificity.
AB  - Pocket proteins retinoblastoma (pRb), p107 and p130 are negative regulators of
      cellular proliferation and multifunctional proteins regulating development,
      differentiation and chromatin structure. The retinoblastoma protein is a potent
      tumor suppressor mutated in a wide range of human cancers, and oncogenic viruses
      often interfere with cell cycle regulation by inactivating pRb. The LxCxE and pRb
      AB groove short linear motifs (SLiMs) are key to many pocket protein mediated
      interactions including host and viral partners. A review of available
      experimental evidence reveals that several core residues composing each motif
      instance are determinants for binding. In the LxCxE motif, a fourth hydrophobic
      position that might allow variable spacing is required for binding. In both
      motifs, flanking regions including charged stretches and phosphorylation sites
      can fine-tune the binding affinity and specificity of pocket protein SLiM
      mediated interactions. Flanking regions can modulate pocket protein binding
      specificity, or tune the high affinity interactions of viral proteins that hijack
      the pRb network. The location of SLiMs within intrinsically disordered regions
      allows faster evolutionary rates that enable viruses to acquire a functional
      variant of the core motif by convergent evolution, and subsequently test numerous
      combinations of flanking regions towards maximizing interaction specificity and
      affinity. This knowledge can guide future efforts directed at the design of
      peptide-based compounds that can target pocket proteins to regulate the G1/S cell
      cycle checkpoint or impair viral mediated pRb inactivation.

PMID- 29370439
TI  - Is It Functional Levels, Obesity, or Something Else?: Making the Case for
      Additional Research Focused on Obesity in Nursing Homes.

PMID- 29370438
TI  - Impact of diffuse large B-cell lymphoma on visits to different provider
      specialties among elderly Medicare beneficiaries: challenges for care
      coordination.
AB  - Newly diagnosed diffuse large B-cell lymphoma (DLBCL) can pose significant
      challenges to care coordination. We utilized a social-ecological model to
      understand the impact of DLBCL diagnosis on visits to primary care providers
      (PCPs) and specialists, a key component of care coordination, over a 3-year
      period of cancer diagnosis and treatment. We used hurdle models and multivariable
      logistic regression with the Surveillance Epidemiology and End Result-Medicare
      linked dataset to analyze visits to PCPs and specialists by DLBCL patients (n =
      5,455) compared with noncancer patients (n = 14,770). DLBCL patients were more
      likely to visit PCPs (adjusted odds ratio, AOR [95% confidence interval, CI]:
      1.25 [1.18, 1.31]) and had greater number of visits to PCPs (beta, SE: 0.384, 
      0.014) than noncancer patients. Further, DLBCL patients were more likely to have
      any visit to cardiologists (AOR [95% CI]: 1.40 [1.32, 1.47]), endocrinologists
      (1.43, [1.21, 1.70]), and pulmonologists (1.51 [1.36, 1.67]) than noncancer
      patients. Among DLBCL patients, the number of PCP visits markedly increased
      during the treatment period compared with the baseline period (beta, SE: 0.491, 
      0.028) and then decreased to baseline levels (-0.464, -0.022). Visits to PCPs and
      specialists were much more frequent for DLBCL patients than noncancer patients,
      which drastically increased during the DLBCL treatment period for chronic care.
      More chronic conditions, treatment side effects, and frequent testing may have
      increased visits to PCPs and specialists. Interventions to improve care
      coordination may need to target the DLBCL treatment period, when patients are
      most vulnerable to poor care coordination.

PMID- 29370441
TI  - Precision Health: Use of Omics to Optimize Self-Management of Chronic Pain in
      Aging.
AB  - Chronic pain has become a public health epidemic based on the number of Americans
      affected and its associated health care costs. Unfortunately, there are few
      efficacious treatments to manage chronic pain and as the population of older
      adults and centenarians who are at high risk for chronic pain continues to grow,
      the chronic pain epidemic will continue to worsen unless new therapeutic
      strategies are discovered. In the current era of precision medicine, there is a
      major emphasis being placed on the use of self-management and omics to discover
      new therapeutic targets and design treatment strategies that are tailored to the
      individual patient. This commentary discusses the current state of the science
      related to omics and self-management of chronic pain in older adults, the role of
      gerontological nurses in this process, and future directions. [Res Gerontol Nurs.
      2018; 11(1):7-13.].

PMID- 29370442
TI  - Response to the Commentary: Precision Health: Using Omics to Optimize Self
      Management of Chronic Pain in Aging: From the Perspective of the NINR Intramural
      Research Program.

PMID- 29370443
TI  - Barriers to Promoting Mobility in Hospitalized Older Adults.
AB  - Hospitalized older adults who do not receive sufficient mobility are more likely
      to sustain negative health outcomes, including higher rates of mortality and
      institutionalization. Accordingly, the purpose of the current secondary data
      analysis was to examine the nurse-promoted mobility of hospitalized older adults
      and the association between nurses' barriers and nurse-promoted mobility. In
      addition, the relationship among patient severity of illness, proxy levels for
      function, and nurse-promoted mobility was examined. The final study sample
      included 61 nurses working in medical units caring for a total of 77 older
      adults. Findings suggest nurse knowledge gaps and attitude barriers could
      potentially influence the type and frequency of mobility they promote in older
      patients. A relationship was found between older patients with impaired mobility
      using assistive devices for mobility at home, and those at high risk for falls
      and nurses promoting more sedentary activity (e.g., chair sitting, walking in the
      room). Interestingly, nurses promoted significantly more sedentary mobility for
      patients with physical therapy orders. [Res Gerontol Nurs. 2018; 11(1):17-27.].

PMID- 29370444
TI  - Older Adult Caregiving in an Amish Community.
AB  - Amish older adults represent a growing and understudied population whose current
      health practices, interactions with health care systems outside of their
      community, and care needs are unknown. Limited research exists on why, when, and
      how Amish older adults and their caregivers experience health care services
      outside of their family and community. The purpose of the current study was to
      describe and explore the perspectives of Amish caregivers caring for older adults
      and their experiences with health care services outside of their community. A
      qualitative phenomenological research design was used in combination with a
      community-based participatory framework with caregivers in a small, rural Amish
      settlement. Amish caregiving of older adults is a complex phenomenon that is
      influenced by cultural characteristics. Caregivers place significant cultural
      value on home caregiving, emphasize the experience as a blessing, and relate
      misunderstandings between themselves and outside health care providers as
      significant concerns. [Res Gerontol Nurs. 2018; 11(1):29-38.].

PMID- 29370445
TI  - "Maybe This Generation Here Could Help the Next Generation": Older African
      American Women's Perceptions on Information Sharing to Improve Health in Younger
      Generations.
AB  - The prevalence of hypertension is highest among African American women, who often
      occupy caregiving roles. The purpose of the current study is to describe
      intergenerational caregiving and communication themes that emerged during focus
      groups with African American older adult women (mean age = 73 years) on
      information sharing and self-management of hypertension. Thematic analysis
      revealed two overarching themes: Caregiving Responsibilities and Improving the
      Health of Younger Generations. Women wanted to help younger generations better
      manage their blood pressures. These findings suggest that intergenerational
      relationships may have an important role in managing health conditions, such as
      hypertension. Further examination of intergenerational relationships as targets
      for blood pressure self-management intervention is warranted to: (a) address the
      need for women to share their wisdom, and (b) help improve blood pressure
      management among African American individuals across the lifespan. [Res Gerontol
      Nurs. 2018; 11(1):39-47.].

PMID- 29370446
TI  - Influence of Nurse Staffing Levels on Resident Weight Loss Within German Nursing
      Homes.
AB  - In Germany, there is no empirical evidence regarding the relationship between
      nurse staffing levels and care outcomes in nursing homes. The current study
      explored differences in nurse staffing levels between facilities with and without
      resident weight loss. The analyses were conducted at the facility level (N = 166)
      and involved weight loss assessment of 8,665 residents. Separate models for
      residents with and without cognitive impairment were computed. The regression
      analyses showed that nursing facilities where no weight loss occurred among
      residents without cognitive impairment had a lower number of residents per RN and
      additional care staff. However, no differences were found between facilities with
      and without weight loss among residents with cognitive disabilities. Further
      research is needed to identify factors leading to weight loss among residents
      with cognitive disabilities, including teamwork and work climate in nursing
      homes. [Res Gerontol Nurs. 2018; 11(1):48-56.].

PMID- 29370447
TI  - Interpersonal Trust and Suicide Ideation Among Adolescent Psychiatric Inpatients:
      An Indirect Effect via Perceived Burdensomeness.
AB  - The identification of theoretically and empirically supported correlates of
      suicide ideation is important to improve treatment approaches to suicide. This
      study sought to examine the association between interpersonal trust
      (theoretically conceptualized as a distal risk marker) and suicide ideation in
      adolescence. Specifically, it was hypothesized that interpersonal trust would be
      negatively associated with suicide ideation via perceived burdensomeness and
      thwarted belongingness (conceptualized as more proximal risk markers). Data were
      drawn from a cross-sectional sample of 387 adolescent inpatients between the ages
      of 12 and 17 years (M = 14.72, SD = 1.49). The sample was 63.6% female, 37.5%
      Hispanic, 26.9% African American/Black, and 25.8% Caucasian. Adolescents
      completed a series of self-report measures to assess thwarted belongingness,
      perceived burdensomeness, interpersonal trust, depressive symptoms, and suicide
      ideation. A structural equation model was fit to the data, and results
      demonstrated a significant indirect path from interpersonal trust to suicide
      ideation via perceived burdensomeness, but not thwarted belongingness. Results
      suggest that interpersonal trust may be a distal risk marker for suicide ideation
      and that interventions to increase interpersonal trust may help prevent the
      development of thwarted belongingness, perceived burdensomeness, and suicide
      ideation.

PMID- 29370448
TI  - Health care professionals' perspective on return to work in cancer survivors.
AB  - OBJECTIVE: Health care professionals play a significant role in cancer survivors'
      decisions regarding return to work (RTW). While there is ample research about
      cancer survivors' views on RTW, little is known about the views of the
      professionals who accompany them from diagnosis to recovery. The study explores
      professionals' perceptions of cancer survivors in the RTW context, as well as
      their views about their own role in the process. METHODS: In-depth interviews (N
      = 26) with professionals specializing in physical or mental health working with
      working-age cancer survivors: occupational physicians, oncologists, oncology
      nurses, social workers, and psychologists specializing in oncology. RESULTS: An
      analysis of the interviews revealed 2 prominent perceptual dimensions among
      professionals: the cancer survivor's motivation to RTW and understanding illness
      related implications upon returning to work. The 2 dimensions imply the following
      4 groups of cancer survivors in the RTW context, as viewed by health
      professionals: the "realist," the "enthusiast," the "switcher," and the
      "worrier." The results also indicate that social workers and psychologists view
      their role in terms of jointly discussing options and implications with the
      cancer survivor, while physicians and nurses view their role more in terms of
      providing information and suggestions. CONCLUSIONS: The training of professionals
      should increase awareness of the assumptions they make about cancer survivors in
      regard to RTW. Additionally, training might elaborate professionals' view of
      their role in the interaction with cancer survivors regarding RTW.

PMID- 29370449
TI  - The impact of parallel regulatory-health technology assessment scientific advice
      on clinical development. Assessing the uptake of regulatory and health technology
      assessment recommendations.
AB  - AIMS: The parallel regulatory-health technology assessment scientific advice
      (PSA) procedure allows manufacturers to receive simultaneous feedback from both
      EU regulators and health technology assessment (HTA) bodies on development plans
      for new medicines. The primary objective of the present study is to investigate
      whether PSA is integrated in the clinical development programmes for which advice
      was sought. METHODS: Contents of PSA provided by regulators and HTA bodies for
      each procedure between 2010 and 2015 were analysed. The development of all
      clinical studies for which PSA had been sought was tracked using three different
      databases. The rate of uptake of the advice provided by regulators and HTA bodies
      was assessed on two key variables: comparator/s and primary endpoint. RESULTS: In
      terms of uptake of comparator recommendations at the time of PSA in the actual
      development, our analysis showed that manufacturers implemented comparators to
      address both the needs of regulators and of at least one HTA body in 12 of 21
      studies. For primary endpoints, in all included studies manufacturers addressed
      both the needs of the regulators and at least one HTA body. CONCLUSIONS: One of
      the key findings of this analysis is that manufacturers tend to implement changes
      to the development programme based on both regulatory and HTA advice with regards
      to the choice of primary endpoint and comparator. It also confirms the
      challenging choice of the study comparator, for which manufacturers seem to be
      more inclined to satisfy the regulatory advice. Continuous research efforts in
      this area are of paramount importance from a public health perspective.

PMID- 29370450
TI  - Imaging-based biomarkers: Changes in the tumor interface of pancreatic ductal
      adenocarcinoma on computed tomography scans indicate response to cytotoxic
      therapy.
AB  - BACKGROUND: The assessment of pancreatic ductal adenocarcinoma (PDAC) response to
      therapy remains challenging. The objective of this study was to investigate
      whether changes in the tumor/parenchyma interface are associated with response.
      METHODS: Computed tomography (CT) scans before and after therapy were reviewed in
      4 cohorts: cohort 1 (99 patients with stage I/II PDAC who received neoadjuvant
      chemoradiation and surgery); cohort 2 (86 patients with stage IV PDAC who
      received chemotherapy), cohort 3 (94 patients with stage I/II PDAC who received
      protocol-based neoadjuvant gemcitabine chemoradiation), and cohort 4 (47 patients
      with stage I/II PDAC who received neoadjuvant chemoradiation and were
      prospectively followed in a registry). The tumor/parenchyma interface was
      visually classified as either a type I response (the interface remained or became
      well defined) or a type II response (the interface became poorly defined) after
      therapy. Consensus (cohorts 1-3) and individual (cohort 4) visual scoring was
      performed. Changes in enhancement at the interface were quantified using a
      proprietary platform. RESULTS: In cohort 1, type I responders had a greater
      probability of achieving a complete or near-complete pathologic response (21% vs
      0%; P = .01). For cohorts 1, 2, and 3, type I responders had significantly longer
      disease-free and overall survival, independent of traditional covariates of
      outcomes and of baseline and normalized cancer antigen 19-9 levels. In cohort 4,
      2 senior radiologists achieved a kappa value of 0.8, and the interface score was
      associated with overall survival. The quantitative method revealed high
      specificity and sensitivity in classifying patients as type I or type II
      responders (with an area under the receiver operating curve of 0.92 in cohort 1,
      0.96 in cohort 2, and 0.89 in cohort 3). CONCLUSIONS: Changes at the
      PDAC/parenchyma interface may serve as an early predictor of response to therapy.
      Cancer 2018;124:1701-9. (c) 2018 The Authors. Cancer published by Wiley
      Periodicals, Inc. on behalf of American Cancer Society. This is an open access
      article under the terms of the Creative Commons Attribution-NonCommercial
      NoDerivs License, which permits use and distribution in any medium, provided the
      original work is properly cited, the use is non-commercial and no modifications
      or adaptations are made.

PMID- 29370451
TI  - Predator identity more than predator richness structures aquatic microbial
      assemblages in Sarracenia purpurea leaves.
AB  - The importance of predators in influencing community structure is a well-studied
      area of ecology. However, few studies test ecological hypotheses of predation in
      multi-predator microbial communities. The phytotelmic community found within the
      water-filled leaves of the pitcher plant, Sarracenia purpurea, exhibits a simple
      trophic structure that includes multiple protozoan predators and microbial prey.
      Using this system, we sought to determine whether different predators target
      distinct microorganisms, how interactions among protozoans affect resource
      (microorganism) use, and how predator diversity affects prey community diversity.
      In particular, we endeavored to determine if protozoa followed known ecological
      patterns such as keystone predation or generalist predation. For these
      experiments, replicate inquiline microbial communities were maintained for seven
      days with five protozoan species. Microbial community structure was determined by
      16S rRNA gene amplicon sequencing (iTag) and analysis. Compared to the control
      (no protozoa), two ciliates followed patterns of keystone predation by increasing
      microbial evenness. In pairwise competition treatments with a generalist
      flagellate, prey communities resembled the microbial communities of the
      respective keystone predator in monoculture. The relative abundance of the most
      common bacterial Operational Taxonomic Unit (OTU) in our system decreased
      compared to the control in the presence of these ciliates. This OTU was 98%
      similar to a known chitin degrader and nitrate reducer, important functions for
      the microbial community and the plant host. Collectively, the data demonstrated
      that predator identity had a greater effect on prey diversity and composition
      than overall predator diversity.

PMID- 29370453
TI  - Terbinafine-induced liver injury may be asymptomatic: need for regular
      monitoring: reply from the authors.

PMID- 29370452
TI  - N-Carboxyanhydride Polymerization of Glycopolypeptides That Activate Antigen
      Presenting Cells through Dectin-1 and Dectin-2.
AB  - The C-type lectins dectin-1 and dectin-2 contribute to innate immunity against
      microbial pathogens by recognizing their foreign glycan structures. These
      receptors are promising targets for vaccine development and cancer immunotherapy.
      However, currently available agonists are heterogeneous glycoconjugates and
      polysaccharides from natural sources. Herein, we designed and synthesized the
      first chemically defined ligands for dectin-1 and dectin-2. They comprised
      glycopolypeptides bearing mono-, di-, and trisaccharides and were built through
      polymerization of glycosylated N-carboxyanhydrides. Through this approach, we
      achieved glycopolypeptides with high molecular weights and low dispersities. We
      identified structures that elicit a pro-inflammatory response through dectin-1 or
      dectin-2 in antigen-presenting cells. With their native proteinaceous backbones
      and natural glycosidic linkages, these agonists are attractive for translational
      applications.

PMID- 29370454
TI  - Health-related quality of life and care satisfaction outcomes: Informing
      psychosocial oncology care among Latina and African-American young breast cancer
      survivors.
AB  - OBJECTIVE: When breast cancer occurs in young women, the medical, physical,
      psychosocial, and overall impacts can be more severe warranting targeted medical
      and psychosocial oncology care. Yet, despite their risk for poorer survival and
      survivorship outcomes, little research has focused on this group with critical
      gaps concerning ethnic minorities who are particularly medically vulnerable.
      Therefore, this preliminary study examined demographic characteristics and
      patient centered outcomes, ie, health-related quality of life (HRQOL), quality
      care satisfaction to inform targeted psychosocial oncology care among African
      American and Latinas young breast cancer survivors (YBCS). METHODS: A total of
      116 African-American and Latina YBCS aged >=21 to 50 years were recruited from
      cancer registries and community agencies. Based on prior research and the
      literature, Latinas were categorized into English language proficient (ELP) and
      Spanish language proficient (SLP) based on their choice of language to conduct
      the study including completion of the measures. RESULTS: SLP Latinas reported
      lower educational attainment and income (P < 0.001) and were more likely to
      report having a mastectomy (P < 0.01) but less likely to report breast
      reconstruction (P < 0.05). Satisfaction with care was correlated with patient
      provider communication and overall HRQOL (P < 0.01) and physical, social/family,
      emotional and functional wellbeing (P < 0.01). SLP Latinas had lower emotional
      wellbeing than African-American YBCS (P < 0.01) and lower functional wellbeing
      than ELP Latina YBCS (P < 0.05). SLP Latina YBCS were less satisfied with their
      care compared with African-American and ELP Latina YBCS (P < 0.01). Financial
      toxicity seems to directly influence both access to care and quality care and
      survivorship outcomes. CONCLUSIONS: Investigating demographic characteristics and
      medical outcomes including HRQOL outcomes and satisfaction with care among ethnic
      minority YBCS is needed to advance the science as well as assist health
      professionals with precision care delivery. Greater translational and patient
      centered research must focus on at-risk population such as YBCS to inform
      precision psychosocial oncology care and reduce health disparities.

PMID- 29370455
TI  - Fertility preservation options in pediatric and adolescent patients with cancer.
AB  - The incidence of childhood cancer has steadily increased since the 1950s, with
      approximately 16,000 children diagnosed each year. However, with the advent of
      more effective multimodal therapies, childhood cancer survival rates have
      continued to improve over the past 40 years, with >80% of patients now surviving
      into adulthood. Fertility preservation (FP) has become an important quality-of
      life issue for many survivors of childhood cancer. As a result, the therapeutic
      options have become less gonadotoxic over time and more patients are being
      offered FP options. This review examines the indications for consultation, male
      and female FP options both in the prepubertal patient and adolescent patient, and
      the unique ethical issues surrounding FP in this vulnerable population. Cancer
      2018;124:1867-76. (c) 2018 American Cancer Society.

PMID- 29370456
TI  - Temporal trends in the risk of second primary cancers among survivors of adult
      onset cancers, 1980 through 2013: An Australian population-based study.
AB  - BACKGROUND: The authors' systematic review indicated an increasing trend in the
      risk of second primary cancers (SPCs) from the 1980s to 2000 when considering
      studies from the United States and Australia. It is uncertain whether this trend
      has continued to increase since 2000. METHODS: The current study was a population
      based study of 51,802 individuals with adult-onset cancers identified in the
      Tasmanian Cancer Registry. Patients with a first cancer diagnosis made between
      1980 and 2009 were followed up to December 2013. SPC risks were quantified using
      standardized incidence ratios (SIRs) and absolute excess risks (AERs). Trends in
      SPC risk were assessed using multivariable Poisson models. RESULTS: With a median
      follow-up of 4.8 years (mean, 6.9 years), a total of 5339 SPCs were observed. The
      SIRs for any SPC increased from 0.98 (95% confidence interval, 0.90-1.07) after a
      first cancer diagnosis in 1980 through 1984 to 1.12 (95% confidence interval,
      1.05-1.20) in 2005 through 2009. In multivariable Poisson models accounting for
      patient sex, age at the time of the first cancer diagnosis, follow-up interval,
      and first cancer type, the trend in SIRs increased significantly from 1980
      through 2009 for all SPCs (P for trend <.001) and for specific SPCs of the head
      and neck, lung, digestive tract, and prostate (all P for trend <.05). From 2000
      onward, the AER for specific SPCs after specific first cancers was highest for
      prostate cancer after first cancers of the urinary tract (AER, 54.3 per 10,000
      person-years). CONCLUSIONS: In Tasmania, the risk of SPCs among survivors of
      adult-onset cancers has increased with periods of first cancer diagnosis from
      1980 through 2009. Increased cancer screening and improved medical imaging may
      have contributed to the greater risk in recent years. Cancer 2018;124:1808-18.
      (c) 2018 American Cancer Society.

PMID- 29370457
TI  - Development of a novel 99m Tc-labeled small molecular antagonist for CXCR4
      positive tumor imaging.
AB  - The chemokine receptor 4 (CXCR4) has been an attractive molecular target for
      tumor imaging, because it is overexpressed in many tumor types and involved in
      tumor progression and metastasis. The purpose of this study is to examine the
      CXCR4 targeting properties of 99m Tc-labeled AMD3465, a small molecule antagonist
      of CXCR4. 99m Tc-AMD3465 was prepared in high yield (>95%) and stable in mice
      serum at least for 4 hours. In vitro cell binding experiments were performed with
      Chinese hamster ovary (CHO), MCF-7 (breast cancer), and CHO-CXCR4 (CHO stably
      transfected to express CXCR4) cell lines. Small animal single photon emission
      computed tomography/computed tomography imaging studies in nude mice bearing MCF
      7 and CHO xenografts showed that the uptakes of the radiotracer in MCF-7 tumors
      were significantly higher than those in the CXCR4-negative CHO tumors (P < 0.05),
      and the MCF-7 tumors uptake could be blocked with an excess of unlabeled AMD3465
      (P < 0.05). These results suggested that 99m Tc-AMD3465 could be a potential
      single photon emission computed tomography radiotracer for CXCR4 imaging.

PMID- 29370458
TI  - Survival by Hispanic ethnicity among patients with cancer participating in SWOG
      clinical trials.
AB  - BACKGROUND: Racial disparities in cancer outcomes have been described. To the
      authors' knowledge, it remains unclear whether patients of Hispanic ethnicity
      have better or worse survival outcomes. In the current study, the authors
      evaluated whether Hispanic participants in SWOG clinical trials had different
      survival outcomes compared with non-Hispanics. METHODS: Adult patients registered
      in SWOG phase 2/3 clinical trials between 1986 and 2012 were analyzed. Studies of
      similar histology and stage of disease were combined. Within each analysis,
      Kaplan-Meier survival curves were generated to examine differences in outcome by
      ethnicity. Multivariate Cox regression was used to estimate the association
      between ethnicity and survival outcomes, controlling for major disease-specific
      prognostic factors and demographic variables plus area-level income and education
      to account for socioeconomic status. RESULTS: A total of 29,338 patients
      registered to 38 trials were included; 5% of these patients were Hispanic.
      Hispanic patients were more likely to be younger and from areas of lower income
      and education (all P<.05). No differences in survival were observed across tumor
      types except in the patients with advanced stage prostate cancer, in whom the
      authors observed an association between Hispanic ethnicity and worse overall
      survival (hazard ratio [HR], 1.40; P = .006), progression-free survival (HR,
      1.36; P = .007), and cancer-specific survival (HR, 1.42; P = .013). After
      adjusting for multiple comparisons, no differences in outcomes were noted.
      CONCLUSIONS: Hispanic patients participating in SWOG trials who received uniform
      treatment and follow-up were found to have similar survival outcomes compared
      with non-Hispanic patients, with the single exception of those patients with
      advanced stage prostate cancer. The results of the current study demonstrate that
      Hispanic patients receiving uniform treatment and follow-up have similar outcomes
      compared with non-Hispanics. Cancer 2018;124:1760-9. (c) 2018 American Cancer
      Society.

PMID- 29370459
TI  - Racial disparities in prostate cancer survival in a screened population: Reality
      versus artifact.
AB  - BACKGROUND: Racial disparities in prostate cancer survival (PCS) narrowed during
      the prostate-specific antigen (PSA) era, suggesting that screening may induce
      more equitable outcomes. However, the effects of lead time and overdiagnosis can
      inflate survival even without real screening benefit. METHODS: A simulation model
      of PCS in the early PSA era (1991-2000) was created. The modeled survival started
      with baseline survival in the pre-PSA era (1975-1990) and added lead times and
      overdiagnosis using estimates from published studies. The authors quantified 1)
      discrepancies between modeled and observed PCS in the PSA era and 2) residual
      period effects on PCS given specified values for screening benefit. RESULTS: Lead
      time and overdiagnosis explained more of the improvement in PCS for older ages at
      diagnosis (46% [95% confidence interval (CI), 44%-50%] for blacks and 51% [95%
      CI, 50%-52%] for all races ages 50-54 years vs 98% [95% CI, 97%-99%] for blacks
      and 100% for all races ages 75-79 years). They also explained more of the
      narrowing in PCS disparities for older ages (33% [95% CI, 31%-43%] for men ages
      50-54 years vs 74% [95% CI, 71%-81%] for men ages 75-79 years). The period
      effects amounted to reductions of 27% to 40% among blacks and 26% to 38% among
      all races in the risk of prostate cancer death, depending on the screening
      benefit. CONCLUSIONS: Real improvements in survival disparities in the PSA era
      are smaller than those observed and reflect similar reductions in the risk of
      prostate cancer death among blacks and all races. Understanding screening
      artifacts is necessary for valid interpretation of observed survival trends.
      Cancer 2018;124:1752-9. (c) 2018 American Cancer Society.

PMID- 29370461
TI  - Religiousness as a Predictor of Suicide: An Analysis of 162 European Regions.
AB  - Research on religion as a protective factor has been marked by four recurrent
      limitations: (1) an overemphasis on the United States, a nation where religiosity
      is relatively high; (2) a neglect of highly secularized zones of the world, where
      religiousness may be too weak to affect suicide; (3) restriction of religiousness
      to religious affiliation, a construct which may miss capturing other dimensions
      of religiousness such as the importance of religion in one's life; and (4) an
      overwhelming use of the nation as a unit of analysis, which masks variation in
      religiousness within nations. The present article addresses these limitations by
      performing a cross-national test of the following hypothesis: The greater the
      strength of subjective religiousness, the lower the suicide rate, using small
      units of analysis for a secularized area of the world. All data refer to 162
      regions within 22 European nations. Data were extracted from two large databases,
      EUROSTAT and the European Social Surveys (ESS Round 4), and merged using NUTS-2
      (Nomenclature of Statistical Territorial Units) regions as the unit of analysis.
      Controls are incorporated for level of economic development, education, and
      measures of economic strain. The results of a multiple regression analysis
      demonstrated that controlling for the other constructs in the model,
      religiousness is associated with lower suicide rates, confirming the hypothesis.
      Even in secularized European nations, where there is a relatively weak moral
      community to reinforce religion, religiousness acts as a protective factor
      against suicide. Future work is needed to explore the relationship in other
      culture zones of the world.

PMID- 29370460
TI  - RNA Cloaking by Reversible Acylation.
AB  - We describe a selective and mild chemical approach for controlling RNA
      hybridization, folding, and enzyme interactions. Reaction of RNAs in aqueous
      buffer with an azide-substituted acylating agent (100-200 mm) yields several 2'
      OH acylations per RNA strand in as little as 10 min. This poly-acylated
      ("cloaked") RNA is strongly blocked from hybridization with complementary nucleic
      acids, from cleavage by RNA-processing enzymes, and from folding into active
      aptamer structures. Importantly, treatment with a water-soluble phosphine
      triggers a Staudinger reduction of the azide groups, resulting in spontaneous
      loss of acyl groups ("uncloaking"). This fully restores RNA folding and
      biochemical activity.

PMID- 29370462
TI  - Integrating Spirituality into MFT Training: A Reflexive Curriculum and
      Qualitative Evaluation.
AB  - When clients enter the therapy room they bring unique spiritual beliefs and
      values in with them; however, marital and family therapists (MFTs) often lack
      training to assist in this important area of diversity. Current training
      recommendations encourage therapists to explore their own spirituality to
      identify personal limitations that may occlude positive client outcomes; however
      very little information exists on the implementation and usefulness of this type
      of training. This article will describe a curriculum and report results from a
      qualitative study of students who participated in a reflexive spirituality
      practicum course offered in a COAMFTE accredited doctoral program at a private,
      religious institution. Through this, we hope to provide a training model to
      further spiritual integration activities in MFT.

PMID- 29370464
TI  - Editorial.

PMID- 29370463
TI  - Dasatinib dose management for the treatment of chronic myeloid leukemia.
AB  - Chronic myeloid leukemia (CML) has evolved into a chronic disease that is managed
      with tyrosine kinase inhibitor therapy. Now that long-term survival has been
      achieved in patients with CML, the focus of treatment has shifted to dose
      optimization, with the goal of maintaining response while improving quality of
      life. In this review, the authors discuss optimizing the dose of the second
      generation tyrosine kinase inhibitor dasatinib. Once-daily dosing regimens for
      dasatinib in the first and later lines of treatment were established through long
      term (5-year and 7-year) trials. Recently published data have indicated that
      further dose optimization may maintain efficacy while minimizing adverse events.
      Results obtained from dose optimization and discontinuation trials currently in
      progress will help practitioners determine the best dose and duration of
      dasatinib for patients with CML, because treatment decisions will be made through
      continued discussions between physicians and patients. Cancer 2018;124:1660-72.
      (c) 2018 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of
      American Cancer Society. This is an open access article under the terms of the
      Creative Commons Attribution-NonCommercial License, which permits use,
      distribution and reproduction in any medium, provided the original work is
      properly cited and is not used for commercial purposes.

PMID- 29370465
TI  - Performance of 4 definitions of childhood elevated blood pressure in predicting
      subclinical cardiovascular outcomes in adulthood.
AB  - We aimed to compare the ability of the pediatric blood pressure (BP) standards
      issued by the US Fourth Report, the recently proposed US, Chinese, and
      international standards to predict adult hypertension and subclinical
      cardiovascular disease (CVD). 2296 children were randomly selected from Beijing
      at baseline. The follow-up survey was conducted among 1177 adults. Subclinical
      adult CVD was assessed using the carotid-femoral pulse wave velocity (cfPWV),
      carotid intima-media thickness (CIMT), and left ventricular mass index (LVMI).
      The prevalence of pediatric elevated BP was significantly higher according to the
      Chinese standards vs the Fourth Report, the updated US standards, and the
      international standards (18.7% vs 14.2%, 17.5%, and 18.0%, respectively; all Ps <
      .001). Children identified as elevated BP using any of the 4 standards were more
      likely to have adult hypertension, high cfPWV, and high LVMI than children
      without elevated BP. However, only the Chinese and updated US standards can
      predict the increased risk of adult high CIMT. Our results indicated that the
      Chinese standards performed equally or better compared with 3 other standards in
      predicting adult hypertension and subclinical CVD.

PMID- 29370466
TI  - Relationship between serum uric acid and blood pressure by adjusting dietary
      factors.

PMID- 29370467
TI  - Efficient analysis of phytochemical constituents in the peel of Chinese wild
      citrus Mangshanju (Citrus reticulata Blanco) by ultra high performance liquid
      chromatography-quadrupole time-of-flight-mass spectrometry.
AB  - An efficient ultra high-performance liquid chromatography coupled with quadrupole
      time-of-flight mass spectrometry method was developed for separation and
      profiling of phytochemical constituents of Chinese wild mandarin Mangshanju
      (Citrus reticulata Blanco). All constituents were well separated within 16 min.
      Based on retention times, accurate mass, MSE fragments, and/or reference
      standards as well as databases, a total of 81 compounds were unambiguously
      identified or tentatively assigned including flavonoid glycosides, acylated
      flavonoid glycosides, flavones, polymethoxylated flavonoids, and limonoids as
      well as four other compounds. Among them, 22 polymethoxylated flavones and ten
      polymethoxylated flavanones/chalcones were identified in Mangshanju, more types
      than other citrus reported before. A basic procedure for identifying flavonoid-O
      glycosides and the aglycones including polymethoxylated flavonoids was proposed.
      In addition, this method was successfully used to analyze another four mandarin
      germplasms, Cenxi suan ju, Xipi gousi gan, Nanfeng miju, and Or, showing that
      Mangshanju contained two characteristic compounds distinct from the other four
      citrus species. This study systematically profiled phytochemical constituents of
      Mangshanju, which was helpful for further utilization of Mangshanju owing to its
      abundant bioactive compounds.

PMID- 29370469
TI  - Central blood pressure variability is increased in hypertensive patients with
      target organ damage.
AB  - We aimed to evaluate the association of aortic and brachial short-term blood
      pressure variability (BPV) with the presence of target organ damage (TOD) in
      hypertensive patients. One-hundred seventy-eight patients, aged 57 +/- 12 years,
      33% women were studied. TOD was defined by the presence of left ventricular
      hypertrophy on echocardiogram, microalbuminuria, reduced glomerular filtration
      rate, or increased aortic pulse wave velocity. Aortic and brachial BPV was
      assessed by 24-hour ambulatory BP monitoring (Mobil-O-Graph). TOD was present in
      92 patients (51.7%). Compared to those without evidence of TOD, they had
      increased night-to-day ratios of systolic and diastolic BP (both aortic and
      brachial) and heart rate. They also had significant increased systolic BPV, as
      measured by both aortic and brachial daytime and 24-hours standard deviations and
      coefficients of variation, as well as for average real variability. Circadian
      patterns and short-term variability measures were very similar for aortic and
      brachial BP. We conclude that BPV is increased in hypertensive-related TOD.
      Aortic BPV does not add relevant information in comparison to brachial BPV.

PMID- 29370468
TI  - Association of ambulatory blood pressure variability with coronary artery
      calcium.
AB  - Blood pressure (BP) variability is associated with progression to clinical
      atherosclerosis. The evidence is inconclusive if BP variability predicts
      cardiovascular outcomes in low-risk populations. The aim of this study was to
      analyze the association of 24-hour BP variability with coronary artery calcium
      (CAC) among a group of individuals without coronary artery disease. The Masked
      Hypertension Study targeted patients with borderline high BP (120-149 mm Hg
      systolic and/or 80-95 mm Hg diastolic). Ambulatory blood pressure monitoring
      (ABPM) was performed at two time-points, 8 days apart. CAC was measured at exit
      visit via cardiac CT and reported as Agatston Score. Weighted standard deviations
      and average real variability were calculated from ABPM. Of the 322 participants
      who underwent cardiac CT, 26% (84) had CAC present, 52% (168) were female, and
      21% (64) were black. BP variability did not differ by CAC group. In this low
      cardiovascular risk group, CAC was not associated with 24-hour ambulatory BP
      variability.

PMID- 29370471
TI  - Saving 100 million lives by improving global treatment of hypertension and
      reducing cardiovascular disease risk factors.

PMID- 29370470
TI  - Association of betaine with blood pressure in dialysis patients.
AB  - Mechanisms underlying elevated blood pressure in dialysis patients are complex as
      a variety of non-traditional factors are involved. We sought to explore the
      association of circulating betaine, a compound widely distributed in food, with
      blood pressure in dialysis patients. We used baseline data of an ongoing cohort
      study involving patients on hemodialysis. Plasma betaine was measured by high
      performance liquid chromatography in 327 subjects. Blood pressure level was
      determined by intradialytic ambulatory blood pressure monitoring. The mean age of
      the patients was 52.6 +/- 11.9 years, and 58.4% were male. Average interdialytic
      ambulatory systolic and diastolic blood pressure were 138.4 +/- 22.7 mm Hg and
      84.4 +/- 12.5 mm Hg, respectively. Mean plasma betaine level was 37.6 MUmol/L.
      Multiple linear regression analysis revealed significant associations of betaine
      with both systolic blood pressure (beta = -3.66, P = .003) and diastolic blood
      pressure (beta = -2.00, P = .004). The associations persisted even after
      extensive adjustment for cardiovascular covariates. Subgroup analysis revealed
      that the association between betaine and blood pressure was mainly limited to
      female patients. Our data suggest that alteration of circulating betaine possibly
      contributes to blood pressure regulation in these patients.

PMID- 29370472
TI  - Arterial hypertension: Unmasking the real risk.

PMID- 29370473
TI  - Carrier ampholyte-free isoelectric focusing on a paper-based analytical device
      for the fractionation of proteins.
AB  - Isoelectric focusing plays a critical role in the analysis of complex protein
      samples. Conventionally, isoelectric focusing is implemented with carrier
      ampholytes in capillary or immobilized pH gradient gel. In this study, we
      successfully exhibited a carrier ampholyte-free isoelectric focusing on paper
      based analytical device. Proof of the concept was visually demonstrated with
      color model proteins. Experimental results showed that not only a pH gradient was
      well established along the open paper fluidic channel as confirmed by pH
      indicator strip, the pH gradient range could also be tuned by the catholyte or
      anolyte. Furthermore, the isoelectric focusing fractions from the paper channel
      can be directly cut and recovered into solutions for post analysis with sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry. This paper-based
      isoelectric focusing method is fast, cheap, simple and easy to operate, and could
      potentially be used as a cost-effective protein sample clean-up method for target
      protein analysis with mass spectrometry.

PMID- 29370475
TI  - A MAP toward increased rates of blood pressure control?

PMID- 29370474
TI  - Renal denervation improves 24-hour central and peripheral blood pressures,
      arterial stiffness, and peripheral resistance.
AB  - Ambulatory blood pressure (BP) and central BP are better predictors for overall
      cardiovascular risk and mortality than brachial BP. Renal denervation (RDN) has
      been shown to reduce office brachial and central BP as well as brachial
      ambulatory BP, but data on central ambulatory BP are limited. Patients (N = 94)
      with treatment resistant hypertension (TRH) who underwent RDN were included.
      Ambulatory BP, including central pressures, hemodynamics, and arterial stiffness
      were measured at baseline and 3, 6, 12 months after RDN by an oscillometric
      device (MobiloGraphTM ). At 3, 6, and 12-month follow-ups, brachial ambulatory BP
      was reduced (P for all < .001). Consistently, central ambulatory BP was reduced
      (P for all < .001). Ambulatory assessed averaged daytime pulse wave velocity
      improved after RDN (P < .05). Total vascular resistance decreased (P for all <
      .01). In patients with TRH, RDN improves brachial and central ambulatory BP,
      arterial stiffness, and total vascular resistance, indicating an improvement of
      cardiovascular outcome.

PMID- 29370476
TI  - Right heart remodeling induced by arterial hypertension: Could strain assessment
      be helpful?
AB  - Left ventricular structural and functional changes in patients with arterial
      hypertension are well established. However, the influence of arterial
      hypertension on right ventricular (RV) remodeling is still being investigated.
      The introduction of strain analysis provided an insight into RV function and
      mechanics. Previous research has demonstrated the predictive value of RV
      longitudinal strain in patients with various cardiovascular conditions, such as
      pulmonary hypertension, heart failure, congenital heart diseases, and valvular
      disease. Nowadays, we are aware of the fact that conventional echocardiographic
      methods usually do not provide necessary information about RV dysfunction in
      patients with arterial hypertension, which is why the evaluation of new
      parameters that could detect RV subtle changes in hypertension is essential. The
      present review article is an overview of the main principles of RV deformation
      and a summary of the current knowledge and clinical significance of RV strain in
      patients with arterial hypertension.

PMID- 29370477
TI  - Prevalence and clinical outcomes of white-coat and masked hypertension: Analysis
      of a large ambulatory blood pressure database.
AB  - The aim of this study was to analyze prevalence and clinical outcomes of the
      following clinical conditions: normotension (NT; clinic BP < 140/90 mm Hg; 24
      hour BP < 130/80 mm Hg), white-coat hypertension (WCHT; clinic BP >= 140 and/or
      >=90 mm Hg; 24-hour BP < 130/80 mm Hg), masked hypertension (MHT; clinic BP <
      140/90 mm Hg; 24-hour BP >= 130 and/or >=80 mm Hg), and sustained hypertension
      (SHT; clinic BP >= 140 and/or >=90 mm Hg; 24-hour BP >= 130 and/or >=80 mm Hg) in
      a large cohort of adult untreated individuals. Systematic research throughout the
      medical database of Regione Lazio (Italy) was performed to estimate incidence of
      myocardial infarction (MI), stroke, and hospitalizations for HT and heart failure
      (HF). Among a total study sample of 2209 outpatients, 377 (17.1%) had NT, 351
      (15.9%) had WCHT, 149 (6.7%) had MHT, and 1332 had (60.3%) SHT. During an average
      follow-up of 120.1 +/- 73.9 months, WCHT was associated with increased risk of
      hospitalization for HT (OR 95% CI: 1.927 [1.233-3.013]; P = .04) and HF (OR 95%
      CI: 3.449 [1.321-9.007]; P = .011). MHT was associated with an increased risk of
      MI (OR 95% CI: 5.062 [2.218-11.550]; P < .001), hospitalization for HT (OR 95%
      CI: 2.553 [1.446-4.508]; P = .001), and for HF (OR 95% CI: 4.214 [1.449-12.249];
      P = .008). These effects remained statistically significant event after
      corrections for confounding factors including age, BMI, gender, smoking,
      dyslipidaemia, diabetes, and presence of antihypertensive therapies.

PMID- 29370478
TI  - Peripheral arterial stiffness as a surrogate of central hemodynamics: A new era
      for cardiovascular risk estimation?

PMID- 29370479
TI  - Medical students' proficiency in performance of the resting ankle-brachial index
      is not sustained at 6 months.

PMID- 29370480
TI  - A patient-specific approach to assessing blood pressure management in patients
      with hypertension and coronary artery disease.
AB  - The objective was to improve the management of patients with hypertension (HTN)
      and coronary artery disease (CAD), utilizing a model which integrates 3
      determinants of coronary blood flow (CBF)-CAD severity, diastolic blood pressure
      (DBP), and left ventricular (LV) mass. We validated non-parametric equations for
      CBF estimation in a consecutive patient sample (N = 81) with HTN and CAD. There
      was a highly significant correlation (r = .565; P < .01) between clinical DBP and
      estimated CBF. Greater LV mass and more severe CAD shifted the relationship
      towards less CBF at the same DBP. LV mass was more critical when DBP >70 mm Hg.
      Estimated changes in CBF at different DBP considering the severity of CAD and LV
      mass can be calculated. In summary, the severity of CAD from coronary CT or
      coronary angiography combined with LV mass from echocardiography permits
      clinicians to guide the extent of, or target for, DBP to avoid seriously
      compromising CBF.

PMID- 29370481
TI  - Relationship between brachial-ankle pulse wave velocity and invasively measured
      aortic pulse pressure.
AB  - Although brachial-ankle pulse wave velocity (baPWV) has been widely used as an
      index of arterial stiffness, no consensus exists about whether baPWV can reflect
      central aortic stiffness. The authors investigated the association between baPWV
      and invasively measured aortic pulse pressure (APP) in a total of 109 consecutive
      patients (mean age, 62.3 +/- 11.3 years; 67.9% men). Most patients (91%) had
      obstructive coronary artery disease, and mean baPWV and APP values were 1535 +/-
      303 cm/s and 66.8 +/- 22.5 mm Hg, respectively. In univariate analysis, there was
      a significant linear correlation between baPWV and APP (r = .635, P < .001). The
      correlation between baPWV and APP remained significant even after controlling for
      potential confounders (beta = 0.574, P < .001; R2  = .469). Arterial stiffness
      measured by baPWV showed a strong positive correlation with invasively measured
      APP, independent of clinical confounders. Therefore, baPWV can be a good marker
      of central aortic stiffness.

PMID- 29370482
TI  - Response to: Relationship between serum uric acid and blood pressure by adjusting
      dietary factors.

PMID- 29370483
TI  - Reconsidering Insomnia as a Disorder Rather Than Just a Symptom in Psychiatric
      Practice.
AB  - Insomnia is a common feature of many psychiatric disorders but can also be a
      comorbid disorder, often contributing to poor outcomes and treatment failure. For
      some patients who do respond to psychiatric treatment, their insomnia persists
      after their mood symptoms have remitted, indicating that their insomnia needs to
      be a separate focus of treatment. In this CME Academic Highlights, Drs Ruth Benca
      and Daniel Buysse discuss how to effectively evaluate patients with psychiatric
      disorders for comorbid insomnia, as well as how to safely and effectively
      implement both behavioral and pharmacologic treatments. .

PMID- 29370484
TI  - Risk of Major Congenital Malformations Associated With the Use of Methylphenidate
      or Amphetamines in Pregnancy.
AB  - The use of prescription psychostimulants during pregnancy has been increasing in
      recent years. One large and 3 small studies have recently examined the risk of
      major congenital malformations following the use of methylphenidate and
      amphetamines during the first trimester of pregnancy. The broad findings of these
      studies are that first trimester gestational exposure to methylphenidate or
      amphetamines is associated with an increased risk of major congenital
      malformations but the associations are no longer statistically significant after
      adjusting analyses for confounding variables; that first trimester exposure to
      amphetamines is not associated with an increased risk of cardiovascular
      malformations; and that first trimester exposure to methylphenidate may increase
      the risk of cardiovascular malformations. A closer look at the data on the last
      mentioned finding, however, suggests that the statistical significance of the
      finding is in doubt and that even if the finding is statistically significant, it
      is probably not clinically significant. Furthermore, all the findings emerged
      from observational studies that cannot exclude confounding by indication and
      other sources of confounding. A reasonable conclusion, therefore, is that there
      is no evidence, at present, to suggest that methylphenidate and amphetamines are
      teratogenic. Nevertheless, because absence of evidence of risk is not evidence of
      absence of risk, the benefits of continuing psychostimulant medication during
      pregnancy should be weighed against potential risks in an individualized and
      shared decision-making process.

PMID- 29370485
TI  - Validity of the Maudsley Staging Method in Predicting Treatment-Resistant
      Depression Outcome Using the Netherlands Study of Depression and Anxiety.
AB  - OBJECTIVE: We investigated if the degree of treatment resistance of depression,
      as measured by the Maudsley Staging Method (MSM), is predictive of a worse
      depression outcome by using a large naturalistic cohort of depressed patients.
      METHODS: 643 subjects from the general population, primary care, and secondary
      care who suffered from current depressive disorder were included from the
      Netherlands Study of Depression and Anxiety baseline assessment. The diagnostic
      criterion was major depressive disorder (MDD) in the last month, based on the
      Composite Interview Diagnostic Instrument (CIDI), or a CIDI diagnosis of MDD in
      the past 6 months with an Inventory of Depressive Symptomatology Self-Report
      score > 24 at baseline. In these subjects, composite scores of the MSM, based on
      duration, severity, and treatment history of current episode, were determined
      retrospectively. We then determined if the MSM score prospectively predicted the
      2-year course of depression after baseline. The primary outcomes were percentage
      of follow-up time spent in a depressive episode and being "mostly depressed" (>=
      50% of the follow-up) between baseline and 2-year follow-up. RESULTS: The MSM
      predicted "percentage of follow-up time with depression" (P < .001) and was
      associated with being "mostly depressed" (OR = 1.40; 95% CI, 1.23-1.60; P <
      .001). These effects were not modified by having received treatment. CONCLUSIONS:
      The current study shows that the MSM is a promising tool to predict worse
      depression outcomes in depressed patients. In this study that adds to previous
      work, we show the applicability of MSM in a wider range of primary and secondary
      care patients with depression.

PMID- 29370486
TI  - [FEMALE STEROID HORMONES - MODULATORS OF IMMUNE RESPONSE TO GENITAL CHLAMYDIA
      TRACHOMATIS INFECTION.]
AB  - In the recent years according to WHO, genital chlamydia is the mos't common
      sexually transmitted infection. Chlamydia Trachomatis is an intracellular
      parasite which target are the tubular epithelial cells of the urethra,
      endocervix, endometrium, endosalpinx, conjunctiva, synovial lining of the joints,
      Glisson's capsule of the liver Our study, as well as some international
      researches, shows that in the cases of genital chlamydia there are changes in the
      ovarian hormones (estradiol and progesterone), their impact on the immune system
      and their importance for the development and the complications of the infection
      with Chlamydia trachomatis. The physiological level of the steroid hormones in
      its turn contributes for the normalization of the local immunity and reduces the
      possibility of recurrences.

PMID- 29370487
TI  - [RISK FACTORS FOR POSTPARTUM OCCULT INJURIES OF THE ANAL SPHINCTER.]
AB  - introduction The overall risk of intrapartum damage the anal sphincter (IUAS) is
      1% of all vaginal births. In contrast, the so-called "occult" anal sphincter
      injuries (OASIS) (defects esablished by endoanal ultrasonography) occur in 33% of
      primiparous women after vaginal birth. Identifying the most common risk factors
      for OASIS can be the basis for selecting high-risk patients. These women should
      be targeted by early pospartum diagnosis and treatment, which could reduce the
      incidence of anal incontinence developed later in life. Objectives To determine
      the role of common risk factors for the occurrence of OASIS in selected
      population. Material and methods The study included 42 patients after vaginal
      birth, born in Maternity Ljubljana in the period January to June 2009, and 38
      patients from July 2009 to November 2011, born in Obstetric Clinic of the
      University Hospital - Pleven, diagnosed with OASIS using endoanal
      ultrasonography. Results We demonstrated that all of the independent variables
      studied in our research (primiparity, gestational age over 41gw and fetal weight
      over 3500 g.) are risk factors for the occurrence of OASIS. Discussion This sudy
      shows that the sudied risk factors for the occurrence of OASIS may be included in
      a clinical practice guideline for eady diagnosis and proper treatment of
      posTpartal injuries affecting the pelvic floor.

PMID- 29370488
TI  - [HISTORY OF GYNECOLOGICAL DISORDERS, OBSTERIC PATHOLOGY AND ANDROGEN LEVELS AS
      PROGNOSTIC FACTORS AND INDICES OF MYOCARDIAL INJURY AMONG POSTMENOPAUSAL WOMEN
      WITH ACUTE CORONARY SYNDROME.]
AB  - The study ob]ective was assessment of pathogenetic and prognostic significance of
      gynecologic and obstetrical pathology and the concentrations of sex steroids in
      adult women with acute coronaty syndrome (ACS). The study group included 120
      postmenopausal women with ACS treated in the Clinic of Cardiology, University
      Hospital "Alexandrovska" between 2011 and 2013. Sex hormones were measured in 57
      patients. Enzyme, electrochemiluminescent, enzyme-linked immunologic and
      immunoturbodimeric methods were used for the examined indices assessment. The
      history for gynecologic disorders and pregnancy complications was associated with
      coronaiy atherosclerotic burden (SYNTAX score - 4,6+/-8,8 vs 8,5+/-9,3, p=0,003),
      gynecologic history only - with lower 17Beta-estradiol levels (139,01+/-167,66 vs
      113,51+/-304,1, p=0,004) and coronaly atherosclerosis severity (5,5+/-9,3 vs
      8,0+/-10,3, p=0,058). Abnormally high endogenous concentrations of androgens were
      found among the patients with ACS with ST elevation, STEMI (27,5% vs 77,8%,
      p=0,004), with significantly more intense acute infiammatoty response (8,7+/-3,21
      vs 11,07+/-2,85, p=0,044 3a WBC) and more extensive acute myocardial damage
      (57,8+/-12,6 vs 45,3 ml, p=O,OO8 for e]ection fraction 33,7+/-37,4 vs 117+/
      144,22 U/L, p=0,031 for CPK-MB; 0,89+/-8 18 vs 1,87+/-0,4 ng/ml, p=0,009 for
      hsTnT). The gynecologic and obstetrical history and hyperandrogenism are related
      to the extent and severity of coronary atherosclerosis, occurrence of STEMI, more
      intense acute inflammatory response and myocardial injury among postmenopausal
      women with ACS.

PMID- 29370489
TI  - [INVESTIGATION ON ANTIFUNGAL SUSCEPTIBILITY OF CANDIDA YEASTS IN PREGNANT
      PATIENTS WITH CONFIRMED VULVOVAGINAL CANDIDIASIS AND THEIR NEWBORNS.]
AB  - Background Vulvovaginal candidiasis (VVU) is considered as a special risk factor
      during pregnancy, with important influence on the reproductive function of the
      patients and on the morbidity in the newborns from mothers with VVC. Maternal VVC
      is a major risk factor for the development of candida-colonization of the infant,
      which in turn is the first step towards the development of mucocutaneous or
      systemic candidiasis and Candida-septicemia in the newborn. In pregnant patients,
      the possible applicable local and systemic medications are limited, while the
      therapeutic resistance in chronic recurrent forms of VVC increases, facts that
      require precision of the diagnosic approach to optimize the therapeutic
      recommendations in pregnant patients, considered as a high risk group. The aim of
      this study was to investigate in vitro antifungal susceptibility of Candida
      yeasts to current antifungal agents in pregnant patients with confirmed VVC
      before the act of birth. Material and Methods Vaginal secretions of 23 healthy
      pregnant women with proven Candida vaginitis were taken within 48 hours before
      birth and the presence of yeasls of Candida was confirmed by culture examination.
      Between 47-72 hours after birth, samples were taken for Candida colonization of
      the oralmucosa and feces of their newborns. Samples were plated on Sabouraud agar
      and cultured in an incubator for 2 to 3 days at a temperature of 25 degrees  C.
      Species identification of the isolated yeasts were performed by commercial API
      Candida test - API 20C AUX (BioMerieux, Marcy-l'Etoile, France). Part of the
      isolates was identified by commercial whale AUXACOLOR (BioRad, Mames la Coquette,
      France). Antifungal sensitivity of isolated strains was examined by applying
      commercial solicitation ready kit and methods of disc diffusion and E-test, as
      the aim of the authors was to assess their potential for use in the diagnosis,
      and the correlation between them. Results Candida albicans was the prevalent
      etiological agent in pregnant patients with VVC immediately before birth (n = 22,
      91.67 +/- 0.06%). Positive Candida colonization was detected in 14 (58.33%) of
      their newborns (n = 24), as no statistically significant difference was
      established, depending on the mode of delivery. The investigated antifungal
      susceptibility with test Fungifast (ELITech Microbiology Reagents), found 100%
      sensitivity of Candida albicans to Amphotericin B, Flucytosin and Voriconazole.
      Intermediate susceptibility to Itraconazole was found in 6 of 23 (26%) maternal
      isolates, and 5 of 23 (22%) isolates were moderately sensitive to Fluconazole.
      Candida krusei showed complete resistance to Fluconazole and Itraconazole. Within
      the group of antifungals for topical application (Econazole, Ketoconazole,
      Miconazole, Nystatin), the results established that 100% of the studied fungi
      were sensitive to Nystatin, while within the groups of azoles for vaginal and
      topical use - C.krusei was 100% resistant, as the sensitivity of C. albicans
      varied between 60-80%. Conclusion Our recommendation, based on the esablished
      results is that in pregnant with uncomplicated VVC as a first-line therapy should
      be considered the group of vaginal azoles and Nystatin, while the systemic
      therapy should be considered carefully and only after the firSt trimester. In
      cases of oral and intestinal candidiasis in neonatology, we recommend a therapy
      with minimal absorbable antifungals as Nystatin and miconazole (amphotericin B is
      available in our country), while systemic antifungal should be initiated only as
      a second choice. The exact etiological diagnosis is especially important because
      in our country there is a tendency for increased incidence of non-albicans fungus
      resistant to therapy, and that changes the therapeutic behavior.

PMID- 29370490
TI  - [LAPAROSCOPIC CERVICOISTHMIC CERCLAGE - OUR EXPERIENCE.]
AB  - The authors share their experience with 7 women to whom a laparoscopic cervical
      cerclage before pregnancy has been placed. No intraoperative or postoperative
      complications were experienced. The indications, technique, positive and negative
      features of vaginal, abdominal and laparoscopic cerclage are discussed.

PMID- 29370491
TI  - [LEFT AND RIGHT UTERINE ARTERY DOPPLER AS EARLY SKREENING TEST OF THREATENED
      ABORTION OUTCOME.]
AB  - Human reproduction entails a fundamental paradox: although critical to the
      survival of the species, many aspects are inefficient and wastage seems
      excessive. Only 50-60% of all conceptions advance beyond 20 weeks of gestation.
      Miscarriage was defined by WHO as a loss of pregnancy before 20 weeks of
      gestation or weight of baby under 500 gr. Threatened abortion is the first,
      reversible phase of miscarriage. The pregnancy outcome doesn't always correlate
      to severe of its cardinal symptoms- vaginal bleeding and abdominal pain. The
      measure of HHG can't accurately predict the pregnancy outcome. Ultrasound
      scanning is probably the best single diagnosic and prognostic test in managing
      cases of threatened abortion. Uterine artery Dopler waveforms analysis in
      patients with threatened abortion is non-invasive method, which can find
      pathological signs in the beginning of pregnancy. Development of a molecular
      biology give an opportunity to find out problems of pregnancy in the process of
      implantation, a technical progress in ultrasound give a chance to sudy changes in
      uterine blood flew in early deadlines and to finding new addictions between
      uterine perfusion and embryo development.

PMID- 29370492
TI  - [DIFFICULTIES IN DISSECTION OF URINARY BLADDER IN TOTAL LAPAROSCOPIC
      HYSTERECTOMY.]
AB  - The dissection of urinary bladder is a crucial phase of the laparoscopic
      operation of hysterectomy. The latter dissection may become even more difficult
      in the context of history of operative interventions as cesarean section or
      cervical conization, presence of cervical or isthmic myomatous nodes, as well as
      upon a bad operative technique. The obeying of some basic principles (knowledge
      of pelvic anatomy and topographic interrelations; considering of present risk
      factors; intraoperative screening for complications and their early treatment)
      results in the optimal performance of laparoscopic hysterectomy.

PMID- 29370493
TI  - [CORIN - NEW HOPE FOR PREDICTION OF PREECLAMPSIA.]
AB  - Preeclampsia is one of the most severe complications of the pregnancy, and trials
      to estimate a panel of predictive markers are of big interest for multiple
      researches. Corin is a transmembrane serine protease, localized in the heart,
      which is converting pro-ANP in to active ANR. ANP is a hormone regulating salt
      haemostasis and arterial bood pressure. Corin-null experimental pregnant mices
      develop arterial hypertention and proteinuria, and increased Corin exprecion in
      to the decidua of human uterus suggests its potential role during pregnancy. It
      is proven it takes place in throphoblast invasion in humans. Further research of
      this brand new marker would've been adding a value in trials to settle a
      effective early screening panel for preeclapmsia prediction, but also would've
      helpful in understanding its complicated pathogenesis. Promising new field for
      research is to evaluate serum corin levels during first trimester in combination
      with other placental factors, markers of neoangiogenesis and Doppler of uterine
      arteries.

PMID- 29370494
TI  - [MENOPAUSE AND CARDIOVASCULAR RISK.]
AB  - Recently, in connection with the increased life expectancy; considerable interest
      in the problems of menopause has risen. The climax is a natural biological period
      of a woman's life during which a decrease in the production of sex hormones
      occurs. In response to the sharp decline in estrogen and altered hormonal
      environment characterizing menopause, a number of unfavourable changes in
      metabolism develop, increasing the risk of cardiovascular disease (CVD) and
      deterioration in the quality of life of menopausal women.

PMID- 29370495
TI  - [SUCCESSFUL LAPAROSCOPIC TREATMENT OF HETEROTOPIC PREGNANCY AFTER ICSI / FREEZE
      EMBRYO TRANSFER - A CASE REPORT.]
AB  - The coexistence of extrauterine and intrauterine or haeterotopic pregnancy (HP)
      is a rare condition with reported incidence of 1 in 8000 to 1 in 30 000
      pregnancies in natural conceived pregnancies, but with the widespread application
      of assisted reproductive technologies (ART) the incidence of HP in women with ART
      has risen to about 0.09% to 1.00%. We have reported a case of a 36 old woman,
      pregnant in 9 gestation week, gravidity 2, 0 para, who have achieved a pregnancy
      after in-vitro fertilization - embryo-transfer of two freeze embryos, developed
      after an ICSI procedure with donor eggs. The patient attended our clinic because
      of acute abdominal pain. She was evaluated by trans-vaginal sonography and
      coexistence of ectopic tubal and intrauterine pregnancy has been confirmed.
      Emergency laparoscopy was carried out. Left tubal ectopic pregnancy and
      hemoperitoneum (1200 ml) were diagnosed. Left salpingectomy was performed. At
      present, the patient is at 24 gestation week and the pregnancy is developing in a
      proper manner. We report such a case due to the increase of the awareness to the
      condition and the possibility of a successful treatment by a laparoscopic
      surgery. Intrauterine pregnancy does not exclude extrauterine pregnancy
      especially in cases after in-vitro fertilization.

PMID- 29370496
TI  - [BOWEL ENDOMETRIOSIS - CASE OF RECTAL LOCALISATION.]
AB  - Endometriosis is a relatively common disease which rarely involves the bowel, and
      even more rarely occurs with intestinal obstruction. Gastrointestinal tract is
      involved in 3 to 37% of women with endometriosis such as the frequency is highest
      in the rectum and the sigma (72%), small intestine (7%), cecum (3.6%) and others.
      Our case concerns 49 years old woman with a picture of secondary intestinal
      obsruction, deepening during the last 2-3 months. An anterior resection of the
      rectum with the closure of the rectal stump has been performed with temporary
      colostoma - due to the severely inflamed and distended colon as a result of
      stenosis about 1 cm in diameter involving the portion from the Bauhin's valve to
      the rectal ampula, caused by two fist-sized tumors in the intestinal wall - on
      the rear and rear-left side of the rectum. Distally, about 2-3 cm of the tumors,
      on the anterior wall of the rectum have been found two plaque-like lesions,
      additionally. The histological result showed that the wall of the colon is
      engaged by transmural endometriosis, involving the mucosa, muskularis propria and
      serosa. The case presented differential diagnostic difficulties to exclude
      malignancy. The benefits of surgical treatment of intestinal endometriosis
      despite the significant volume of conducted surgery should not be underestimated,
      as with medication, it significantly improves clinical symptoms and quality of
      life.

PMID- 29370497
TI  - [TREATMENT WITH INO OF INFANTS WITH PPHN.]
AB  - PPHN is a life threatening disease that appears as a result of high pulmonary
      vascular resistance and persistent right to left shunt across foramen ovale and
      ductus arteriosus. The treatment of PPHN is complex and often ineffective. iNO is
      important part of the pathogenetic treatment of the disease. We present six
      infants with PPHN treated with iNO. The clinical effect of the drug was quick and
      the hemodynamics stabilized. All infants survived without side effects and with
      better neurodevelopment outcome.

PMID- 29370498
TI  - [The Role of Chlamydia Trachomatis in Pregnant Women with Endocervicitis.]
AB  - Infectious endocervicitis is a common disease in women of reproductive age. Itis
      of great clinical importance because the infection can spread over the genital
      tract and it can transfer both in horisontal way (sexual partner) and vertical
      way (foetus and new-bom). One of the most common causers for the infections
      endocervicitis is Chlamydia trachomatis. The aim of the study was to define the
      frequency of the chlamydial endocervicitis among women with desired pregnancy and
      examining them while pregnant and until the birth to define the possible
      complications.

PMID- 29370499
TI  - [Laparoscopic Operations in Ovarian Endometriosis.]
AB  - OBJECTIVE: The Sudy aimed to analyze performed laparoscopic operations in ovarian
      endometriosis. MATERIAL AND METHODS: A retrospective study was carried out
      including 336 patients with pelvic endometriosis who were operated
      laparoscopically in St.Marina Hospital - Pleven from January 2008 to July 2014.
      RESULTS AND DISCUSSION: The ovaries are the pelvic organs most affected (76%) by
      endometriosis. The most done intervention is laparoscopic cystectomy (64.9%),
      followed by cystadnexectomy- (6,8%). The rarest are radical interventions -
      laparoscopic hysterectomies with adnexa (4.8%). CONCLUSION: The size of the
      endometriotic cyst, the severity of disease, the age and the reproductive
      condition are crucial for makina decisions concernina the extent of suraical
      intervention.

PMID- 29370500
TI  - [Preparation of Cervical Dilatation Before with Misoprostol and Laminaria -
      Advantages and Disadvantages.]
AB  - The surgical hysteroscopy became popular as a minimally invasive approach to
      interuterine changes. Dilatation is a real challenge during surgical hyseroscopy
      especially in first delivery patients, women in menopause and women with cervical
      stenosis. Apart from this, some long hysteroscopy operations such as myomectomy
      require adequate dilatation in order to facilitate the multiple insertions and
      drawing pulling of the resectoscope. Another technical problem is the need for a
      significant degree of cervical dilatation, as well as softening of the cervix,
      which will allow the extraction of the excised endometrial polyps or myomatose
      parts. Mysoprostol is analogous to prostaglandin El, which is commonly used in
      obstetrics to induce an abortion and birth, as well as after birth to control the
      excessive vaginal bleeding. Its use in gynecology is limited. In our study it is
      of vital importance. The vaginal administration of MysoproStol before surgical
      hysteroscopy facilitates dilatation. The eased hysteroscopy minimizes cervical
      complications. On the other hand, the natural dilatators Laminaria, made of
      Laminariajaponica orLaminaria Digitata sticks, are attractive natural substances
      which can cause dilatation with minimally observed systemic side effects. They
      have shown efficient results during the cervical preparation before surgical
      hysteroscopy. Despite of that, there are no comparative studies on the efficiency
      of the two methods for cervical preparation. The aim of this Study is to compare
      the efficacy of internally vaginal Mysoprostol against endocervical dilatators
      Laminaria before surmical hvSterosconv in certain cases.

PMID- 29370501
TI  - [New Low-Dose Oral Contraceptive with 28 Midiana.]
AB  - As a representative of the low dose generation of oral contraceptives, Midiana 28
      provides minimal intake of estrogens for the female organism in the presence of a
      new generation getation component- Drospierenone. Midiana has an excellent
      contraceptive effect - the control group of women showed no cases of impregnation
      during the intake, Pearl index =0.00. It also exercises a good control over the
      menstrual cycle with low frequency of intementrual bleeding /17%/ Midiana 28
      shows a very good tolerability with minimal, detected, rapidly transient side
      effects.

PMID- 29370502
TI  - [Ultrasound Examination and Management of Twin Pregnancy.]
AB  - : Twin pregnancies are found in about 3 % of all pregnancies and 2/3 are
      dizygotic and 1/3 are monozygotic. In the last 30 years after the introduction of
      assisted conception and increasing maternal age the rate of twin pregnancies
      dramatically increased. Compared to singletons, twins have more complications
      such as intrauterine demise, intrauterine selective fetal growth reStriction,
      congenital anomalies, miscarriage and preterm labour. Monochorionic twins are at
      high risk for unique complications because of blood exchange through vascular
      communications in the shared placenta. Twin pregnancies should be considered as a
      high risk pregnancies and the well-being of the two fetuses should be taken into
      account with a strict protocol for follow up and management options. CONCLUSION:
      Ultrasound examination olavs a maior role in fetal surveillance.

PMID- 29370504
TI  - [Intrauterine Fetal Growth Restriction- Screening Model. Literature Review.]
AB  - Placental dysfunction is involved in a spectrum of obs.tetric conditions
      including preeclampsia, placental abrution and intrauterine fetal growth
      restriction. Their timely and accurate recognition is often a chalange since
      diagnostic criteria are dill based on nonspecific signs and symptomes. Fetal
      growth restriction (FGR) refers to a fetus that has failed to achieve its
      genetically determined growth potential and affects up to 5-10% of pregnancies.
      FRR is associated with an increase in perinatal mortality and morbidity. The
      diagnoslic challenge is in distinguishing SGA pregnancies from FGR pregnancies
      because the majority of SGA pregnancies are associated with a good prognosis
      compared to FGR pregnancies. Multifetal gegations have a high incidence of FGR.
      About 20-30% of dichorionic twins will suffer from FGR, as will 40% of
      monochorionic twins. Ultrasound is the benchmark for accurate pregnancy dating
      and diagnosis of FGR. However, there is room for error and FGR is undetected in
      about 30% of routinely scanned cases and incorrectly detected in 50% of cases. In
      recent years, the main priority of the leading obstetric clinics in Europe and
      the USA is drafting a universal screening model for selecting patients at high
      risk of developing placental dysfunction. Now, this model is part of the standard
      screening for chromosomal aneuploidies in the firs and second trimester of
      pregnancy and prolonged screening in the second and third trimester in patients
      at high risk.

PMID- 29370503
TI  - [Chemotherapy for Malignancy During Pregnancy - Literature Review.]
AB  - In today's dynamic development of modern life, we can unfortunately see more and
      more often cases of malignant diseases during pregnancy. Therapy of these
      conditions in pregnant women is a challenge to the doctors, due to concerns for
      the mother's health, but also the possible risks for the foetus. An additional
      difficulty is the fact that there are no common algorithms for the treatment. Of
      great importance is the ges'tation period, because in its different parts, the
      risks vary in grade. It is believed that up to 10-12th ges.tation week
      chemotherapy should not be included. The optimal time for the last course is 35th
      gestation week or three weeks to the due date. The purpose of this review is to
      examine the benefits and risks of the treatment of malignant diseases during
      pregnancy for both the mother and the fetus.

PMID- 29370505
TI  - [Antibodies Against Immunologically Sequestered Antigens in Patients with
      Polycystic Ovary Syndrome (PCOS).]
AB  - Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility.
      In recent times, autoimmune processes are supposed to play a role in a number of
      conditions with unexplained etiology. This includes some cases of human
      infertility. The attempts to detect antiovarian antibodies in patients with PCOS
      generally produced negative results. Presence of non-organ specific
      autoantibodies in patients with polycytosis has been reported, but the data are
      till inconsistent. Meanwhile, a number of recent sludies reveal a correlation
      between PCOS, hypothyroidism (manifested or subclinical) and autoimmunity. In
      this respect, many authors recommend thyroid function to be regularly checked in
      patients with PCOS. There are data that certain categories of women with
      polycystosis show an elevated concentration of antisperm antibodies. The problem
      is an interesting example how a pathological process can elucidate the complex
      interactions between the immune system and various compartments of the endocrine
      system that include immunologically isolated antigens.

PMID- 29370506
TI  - [Introduction to Epileptology for Specialists of Obstetrics and Gynecology.]
AB  - Epilepsy is the most common serious chronic neurological desease during
      pregnancy. It treatment is a big challenge for the neurologists but in higher
      degree for the gynecologists. Very oftej in our practice we have unfronted to the
      notion of the pregnant women with epilepsy (PWWE) that he gynecologist is fully
      responsible for both-her pregnancy and her epilepsy and their interconnected
      effects This idea was often inculcated by some regional neurologists that are not
      familiar with the problems arisin( in connection with one PWWE. The gynecologists
      should know also the legal aspects deriving from failure during pregnancy of
      women with epilepsy. Therefore, in the next several pages, based on ourlong
      9tandin( practical experience and theoretical knowledge, we tried to summarize
      the mot important specialize( medical information that/which should be known by
      every gynecologisIt for epilepsy and epileptic seizure. when we helds the
      treatment of PWWE.

PMID- 29370507
TI  - [A Case of Isolated Massive Pre-sacral Lymph Node Metastasis in 1B1 Stage
      Cervical Cancer - Case Report.]
AB  - The article presents a rare case of isolated massive pre-sacral metastasis in
      first stage cervical cancer. A 64 year old patient, which on occasion genital
      bleeding is made D&CI and histologically proven a "cancer of the cervix." Last
      period - 6 years ago. Clinically a patient diagnosed as IBI stage according to
      FIGO criteria. Surgery was radical hysterectomy (Class Ill) and pelvic and
      paraaortic lymph node dissection. HiStological result of the preparation is:
      vagina - clean resection lines, parameters - connective tissue and vessels,
      endometrium - atrophic changes, paraaortic lymph nodes - without metastases,
      cervix - infiltrative ulcerous adenosquamous carcinoma size vertically -4 cm. and
      -3.5 cm horizontally. Hitopathological diagnosis confirmed the clinical -
      pTlblNlMx.

PMID- 29370508
TI  - [Treatment of PPHN with iNO in an Infant with Trombophilia and Thrombus in PDA.
      Clinical Case.]
AB  - PPHN is common in 1-2/1000 newborn infants. The morbidity and mortality
      accompanying the disease are extremely high. The treatment is frequently
      ineffective. The therapy with iNO is the fir l strategy based therapy of PPHN. We
      present the clinical case of an infant with congenital pneumonia and secondary
      PPHN treated with iNO. During the clinical observation of the infant congenital
      trombophilia was diagnosed, due to the presence of a thrombus in PDA. The outcome
      was favorable.

PMID- 29370509
TI  - Colloid Carcinoma of the Uterine Cervix and Its Immunohistochemical Analysis: A
      Case Report.
AB  - Colloid carcinoma, which is a very rare tumor of the uterine cervix, is composed
      of an excessive amount of mucus and a relative paucity of tumoral glandular cells
      within them. Herein, we report a rare case of colloid carcinoma of the cervix
      with adenocarcinoma in situ (AIS), intestinal and usual types, and endocervical
      adenocarcinoma (usual type) components. We also discuss the morphological and
      immunohistochemical characteristics of this tumor. A 51-year-old woman was
      referred to our outpatient clinic with the symptom of genital bleeding lasting
      for 5 months. She had a cervix surrounded by an irregular tumor with a diameter
      of 5 cm. The colloid carcinoma cells were positive for MUC2, MUC5AC, and
      cytokeratin (CK) 7, focal positive for CDX2, and negative for MUC6 and CK20.
      Also, the intestinal type AIS showed a similar staining pattern. Colloid
      carcinoma cells producing mucin showed an intestinal phenotype and AIS. The
      intestinal type can be considered as a precursor lesion of colloid carcinoma.

PMID- 29370510
TI  - Importance of Individual Ghost Cells in Fine-Needle Aspiration Cytology Diagnosis
      of Pilomatricoma.
AB  - BACKGROUND: Although histological diagnosis of pilomatricoma is not difficult
      because of its unique histological features, cytological diagnosis through fine
      needle aspiration cytology (FNAC) is often problematic due to misdiagnoses as
      malignancy. METHODS: We reviewed the cytological features of 14 cases of
      histologically-proven pilomatricoma from Korea Cancer Center Hospital, with a
      discussion on the diagnostic pitfalls of FNAC. RESULTS: Among 14 cases of
      pilomatricoma, 10 (71.4%) were correctly diagnosed through FNAC, and two (14.3%)
      were misdiagnosed as carcinoma. Cytologically, all cases had easily recognizable
      clusters of basaloid cells and foreign body-type multinucleated cells. Although
      ghost cells were also found in all cases, some were inconspicuous and hardly
      recognizable due to their small numbers. CONCLUSIONS: An accurate diagnosis of
      pilomatricoma in FNAC is feasible with consideration of clinical information and
      close examination of ghost cells.

PMID- 29370512
TI  - Self-Assembly Template Driven 3D Inverse Opal Microspheres Functionalized with
      Catalyst Nanoparticles Enabling a Highly Efficient Chemical Sensing Platform.
AB  - The design of semiconductor metal oxides (SMOs) with well-ordered porous
      structure has attracted tremendous attention owing to their larger specific
      surface area. Herein, three-dimensional inverse opal In2O3 microspheres (3D-IO
      In2O3 MSs) were fabricated through one-step ultrasonic spray pyrolysis (USP)
      which employed self-assembly sulfonated polystyrene (S-PS) spheres as a
      sacrificial template. The spherical pores observed in the 3D-IO In2O3 MSs had
      diameters of about 4 and 80 nm. Subsequently, the catalytic palladium oxide
      nanoparticles (PdO NPs) were loaded on 3D-IO In2O3 MSs via a simple impregnation
      method, and their gas sensing properties were investigated. In a comparison with
      pristine 3D-IO In2O3 MSs, the 3D-IO PdO@In2O3 MSs exhibited a 3.9 times higher
      response (Rair/Rgas = 50.9) to 100 ppm acetone at 250  degrees C and a good
      acetone selectivity. The detection limit for acetone could extend down to ppb
      level. Furthermore, the 3D-IO PdO@In2O3 MSs-based sensor also possess good long
      term stability. The extraordinary sensing performance can be attributed to the
      novel 3D periodic porous structure, highly three-dimensional interconnection,
      larger specific surface area, size-tunable (meso- and macroscale) bimodal pores,
      and PdO NP catalysts.

PMID- 29370511
TI  - Extracellular Vesicles and the Promise of Continuous Liquid Biopsies.
AB  - The rapid and accurate diagnosis of patients with minimally invasive procedures
      was once only found in science fiction. However, the discovery of extracellular
      vesicles (EVs) and their near ubiquity in body fluids, coupled with the advent of
      inexpensive next generation sequencing techniques and EV purification protocols,
      promises to make science fiction a reality. Purifying and sequencing the RNA
      content of EV from routine blood draws and urine samples are likely to enable
      pathologists and physicians to diagnose and track the progress of diseases in
      many inaccessible tissues in the near future. Here we present the evolutionary
      background of EV, summarize the biology of EV formation and cargo selection, and
      discuss the current barriers to making continuous liquid biopsies through the use
      of EV a science reality.

PMID- 29370513
TI  - Imidazole-2yl-Phosphonic Acid Derivative Grafted onto Mesoporous Silica Surface
      as a Novel Highly Effective Sorbent for Uranium(VI) Ion Extraction.
AB  - A new imidazol-2yl-phosphonic acid/mesoporous silica sorbent (ImP(O)(OH)2/SiO2)
      was developed and applied for uranium(VI) ion removal from aqueous solutions. The
      synthesized material was characterized by fast kinetics and an extra-high
      adsorption capacity with respect to uranium. The highest adsorption efficiency of
      U(VI) ions was obtained for the reaction system at pH 4 and exceeded 618 mg/g.
      The uranium(VI) sorption proceeds quickly in the first step within 60 min of the
      adsorbent sites and ion interactions. Moreover, the equilibrium time was
      determined to be 120 min. The equilibrium and kinetic characteristics of the
      uranium(VI) ions uptake by synthesized sorbent was found to follow the Langmuir
      Freundlich isotherm model and pseudo-second-order kinetics rather than the
      Langmuir, Dubinin-Radushkevich, and Temkin models and pseudo-first-order or
      intraparticle diffusion sorption kinetics. The adsorption mechanism for uranium
      on the sorbent was clarified basing on the X-ray photoelectron spectroscopy (XPS)
      analysis. The model of UO22+ binding to surface of the sorbent was proposed
      according to the results of XPS, i.e., a 1:1 U-to-P ratio in the sorbed complex
      was established. The regeneration study confirms the ImP(O)(OH)2/SiO2 sorbent can
      be reused. A total of 45% of uranium ions was determined as originating from the
      sorbent leaching in the acidic solutions, whereas when the basic solutions were
      used, the removal efficiency was 12%.

PMID- 29370514
TI  - Can CRISPR-Based Gene Drive Be Confined in the Wild? A Question for Molecular and
      Population Biology.
AB  - The recent discovery of CRISPR and its application as a gene editing tool has
      enabled a range of gene drive systems to be engineered with greater ease. In
      order for the benefits of this technology to be realized, in some circumstances
      drive systems should be developed that are capable of both spreading into
      populations to achieve their desired impact and being recalled in the event of
      unwanted consequences or public disfavor. We review the performance of three
      broad categories of drive systems at achieving these goals: threshold-dependent
      drives, homing-based drive and remediation systems, and temporally self-limiting
      systems such as daisy-chain drives.

PMID- 29370515
TI  - Water-Soluble Organic Composition of the Arctic Sea Surface Microlayer and
      Association with Ice Nucleation Ability.
AB  - Organic matter in the sea surface microlayer (SML) may be transferred to the
      atmosphere as sea spray and hence influence the composition and properties of
      marine aerosol. Recent work has demonstrated that the SML contains material
      capable of heterogeneously nucleating ice, but the nature of this material
      remains largely unknown. Water-soluble organic matter was extracted from SML and
      underlying seawater from the Arctic and analyzed using a combination of mass
      spectrometric approaches. High performance liquid chromatography-ion trap mass
      spectrometry (LC-IT-MS), and Fourier transform ion cyclotron resonance MS (FT-ICR
      MS), showed seawater extracts to be compositionally similar across all stations,
      whereas microlayer extracts had a different and more variable composition. LC-IT
      MS demonstrated the enrichment of particular ions in the microlayer. Ice
      nucleation ability (defined as the median droplet freezing temperature) appeared
      to be related to the relative abundances of some ions, although the extracts
      themselves did not retain this property. Molecular formulas were assigned using
      LC-quadrupole time-of-flight MS (LC-TOF-MS2) and FT-ICR-MS. The ice nucleation
      tracer ions were associated with elevated biogenic trace gases, and were also
      observed in atmospheric aerosol collected during the summer, but not early spring
      suggesting a biogenic source of ice nuclei in the Arctic microlayer.

PMID- 29370517
TI  - Immobilized Seed-Mediated Growth of Two-Dimensional Array of Metallic
      Nanocrystals with Asymmetric Shapes.
AB  - Bottom-up fabrication of such arrays with specific orientation of nanoparticles
      remains a challenge. In this paper, we report an immobilized seed-mediated growth
      strategy for the fabrication of two-dimensional (2D) arrays of mono- and
      bimetallic polyhedral nanocrystals with well-defined shapes and orientations on a
      substrate. This method relies on the controlled solution-phase deposition of
      metals (i.e., Au and Pd) on a selectively exposed surface of self-assembled seed
      nanoparticles that are immobilized on a substrate through collapsed polymer
      brushes. By using this approach, we demonstrated the preparation of various 2D
      arrays of shaped Au nanocrystals and Au core/Pd shell nanocrystals with
      asymmetric geometry of two halves and controlled orientations with respect to the
      substrate. The shape evolution of seeds to final nanocrystals was systematically
      monitored and evaluated by electron microscopic imaging. Our study suggests that
      the shape and orientation of nanocrystals within arrays is determined by the
      preferential orientation of assembled seed nanoparticles on the substrate and
      controllable deposition of metals on exposed crystal facets of immobilized seeds.
      The synthetic approach we developed presents an important addition to current
      tools for the fabrication of substrate-supported functional nanostructures.

PMID- 29370516
TI  - Few-Layer Antimonene: Anisotropic Expansion and Reversible Crystalline-Phase
      Evolution Enable Large-Capacity and Long-Life Na-Ion Batteries.
AB  - Two-dimensional (2D) antimonene is a promising anode material in sodium-ion
      batteries (SIBs) because of its high theoretical capacity of 660 mAh g-1 and
      enlarged surface active sites. However, its Na storage properties and
      sodiation/desodiation mechanism have not been fully explored. Herein, we propose
      the sodiation/desodiation reaction mechanism of 2D few-layer antimonene (FLA)
      based on results acquired by in situ synchrotron X-ray diffraction, ex situ
      selected-area electron diffraction, and theoretical simulations. Our study shows
      that the FLA undergoes anisotropic volume expansion along the a/b plane and
      exhibits reversible crystalline phase evolution (Sb ? NaSb ? Na3Sb) during
      cycling. Density-functional theory calculations demonstrate that the FLA has a
      small Na-ion diffusion barrier of 0.14 eV. The FLA delivers a larger capacity of
      642 mAh g-1 at 0.1 C (1 C = 660 mA g-1) and a high rate capability of 429 mAh g-1
      at 5 C and maintains a stable capacity of 620 mA g-1 at 0.5 C with 99.7% capacity
      retention from the 10th to the 150th cycle. Considering the 660 mAh g-1
      theoretical capacity of Sb, the electrochemical utilization of Sb atoms of FLA is
      as high as 93.9% at a rate of 0.5 C for over 150 cycles, which is the highest
      capacity and Sb utilization ratio reported so far. Our study discloses the Na
      storage mechanism of 2D FLA, boosting promising applications of 2D materials for
      advanced SIBs.

PMID- 29370518
TI  - Low-Temperature Copper Bonding Strategy with Graphene Interlayer.
AB  - The reliability of lead-free Cu bonding technology is often limited by high
      bonding temperature and perpetual growth of intermetallic compounds between Sn
      solder and Cu substrate. Here, we report a low-bonding-temperature and highly
      reliable Cu bonding strategy with the use of graphene as an interlayer. By
      integrating a nanoscale graphene/Cu composite on the Cu substrate prior to
      thermocompression bonding, we observe a macroscale phenomenon where reliable Sn
      Cu joints can be fabricated at a bonding temperature as low as 150  degrees C.
      During the bonding process, nanoscale features are replicated in the Sn solder by
      the Cu nanocone array morphology. Compared to microscale Sn, nanoscale Sn is
      mechanically weaker and thus can distribute on the Cu substrate at a much lower
      temperature. Furthermore, insertion of a graphene interlayer, which is one atom
      thick, can successfully retard the intermetallic compounds' growth and preserve a
      high bonding yield, following 96 h of aging, as confirmed through SEM and shear
      strength analyses. Our graphene-based Cu bonding strategy demonstrated in this
      work is highly reliable, cost-effective, and environmentally friendly,
      representing a much closer step toward industrial applications.

PMID- 29370519
TI  - Influence of Solvent Swelling on Ultrafast Structural Dynamics in
      Polydimethylsiloxane Thin Films by Two-Dimensional IR Spectroscopy.
AB  - Fourier transform infrared and two-dimensional IR (2D-IR) spectroscopies were
      applied to polydimethylsiloxane (PDMS) cross-linked elastomer and a siloxane
      oligomer without solvent and swollen or dissolved in various solvents. The
      silicon hydride, which is covalently bound to the polymer chains, was the
      vibrational probe for the systems studied. There is almost an absence of
      vibrational solvatochromism in these systems. Frequency-frequency correlation
      functions obtained by 2D-IR spectroscopy show that the insensitivity of the FTIR
      spectra is due to overwhelming heterogeneity. However, the homogeneous
      contribution to the FTIR spectrum is smaller for the elastomer than the oligomer
      showing that the cross-linking process restricts the frequency fluctuations that
      are experienced by the hydride mode. The silicon hydride mode in a cross-linked,
      solvent-free PDMS film also exhibits spectral diffusion that must be due to
      polymer structural motions on the ultrafast time scale that are active above the
      glass transition temperature. Once solvents penetrate and swell the elastomer,
      the polymer likely continues to experience these polymer structural motions.
      However, we find that the vibrational dynamics are characteristic of the
      infiltrating solvents, showing that at least some fraction of the measured
      dynamics originate in solvent motions.

PMID- 29370520
TI  - Magnetic Field Facilitated Resilient Chain-like Fe3O4/C/Red P with Superior
      Sodium Storage Performance.
AB  - Red phosphorus (P) has recently attracted lots of interest due to its
      extraordinary theoretical capacity of 2596 mAh g-1 in sodium-ion batteries
      (SIBs). However, it is challenging to solve the stability in the preparation
      process, while enhancing its low conductivity and solving the structural
      degradation caused by the enormous volume expansion (>490%) during cycling have
      become the targeted pursuits. Here, we creatively introduced the magnetic stimuli
      source to solve both of the preparation and the volume swelling force issues. In
      the precedence of magnetic field, the increased pressure in the sample room
      drives the homogeneous red P particles to finely deposit on the surface of
      Fe3O4/C. The chain-like Fe3O4/C/red P was successfully prepared assisted by the
      magnetic field. Simultaneously, considering that the speeded up movements for
      both electrons and sodium ions depended on Lorentz force, the electrochemical
      performance of such anode material is optimized by tuning the arrays in
      collector. It is noted that the nanostructure is elastically rearranged for the
      resistance of volume swelling force. Compared with the single Fe3O4/C/red P
      particles, for the magnetic fabricated Fe3O4/C/P chain structure, the
      electrostatic potential for reconstructing the chain-like Fe3O4/C/P is the
      largest. Such configured chain-like anode material exhibits an extraordinary
      cyclic performance and superior rate capability (692 mAh g-1 at 2000 mA g-1). The
      magnetic stimuli source bridges both the preparation optimization and the
      electrochemical performance enhancements for the red P based anode materials.

PMID- 29370521
TI  - Interpolative Separable Density Fitting through Centroidal Voronoi Tessellation
      with Applications to Hybrid Functional Electronic Structure Calculations.
AB  - The recently developed interpolative separable density fitting (ISDF)
      decomposition is a powerful way for compressing the redundant information in the
      set of orbital pairs and has been used to accelerate quantum chemistry
      calculations in a number of contexts. The key ingredient of the ISDF
      decomposition is to select a set of nonuniform grid points, so that the values of
      the orbital pairs evaluated at such grid points can be used to accurately
      interpolate those evaluated at all grid points. The set of nonuniform grid
      points, called the interpolation points, can be automatically selected by a QR
      factorization with column pivoting (QRCP) procedure. This is the computationally
      most expensive step in the construction of the ISDF decomposition. In this work,
      we propose a new approach to find the interpolation points based on the
      centroidal Voronoi tessellation (CVT) method, which offers a much less expensive
      alternative to the QRCP procedure when ISDF is used in the context of hybrid
      functional electronic structure calculations. The CVT method only uses
      information from the electron density and can be efficiently implemented using a
      K-Means algorithm. We find that this new method achieves comparable accuracy to
      the ISDF-QRCP method, at a cost that is negligible in the overall hybrid
      functional calculations. For instance, for a system containing 1000 silicon atoms
      simulated using the HSE06 hybrid functional on 2000 computational cores, the cost
      of the QRCP-based method for finding the interpolation points is 38.1 s, while
      the CVT procedure only takes 0.7 s. We also find that the ISDF-CVT method
      enhances the smoothness of the potential energy surface in the context of ab
      initio molecular dynamics (AIMD) simulations with hybrid functionals.

PMID- 29370522
TI  - Occupied-Orbital Fast Multipole Method for Efficient Exact Exchange Evaluation.
AB  - We present an efficient algorithm for computing the exact exchange contributions
      in the Hartree-Fock and hybrid density functional theory models on the basis of
      the fast multipole method (FMM). Our algorithm is based on the observation that
      FMM with hierarchical boxes can be efficiently used in the exchange matrix
      construction, when at least one of the indices of the exchange matrix is
      constrained to be an occupied orbital. Timing benchmarks are presented for alkane
      chains (C400H802 and C150H302), a graphene sheet (C150H30), a water cluster
      [(H2O)100], and a protein Crambin (C202H317O64N55S6). The computational cost of
      the far-field exchange evaluation for Crambin is roughly 3% that of a self
      consistent field iteration when the multipoles up to rank 2 are used.

PMID- 29370523
TI  - Revealing the Penumbra through Imaging Elemental Markers of Cellular Metabolism
      in an Ischemic Stroke Model.
AB  - Stroke exacts a heavy financial and economic burden, is a leading cause of death,
      and is the leading cause of long-term disability in those who survive. The
      penumbra surrounds the ischemic core of the stroke lesion and is composed of
      cells that are stressed and vulnerable to death, which is due to an altered
      metabolic, oxidative, and ionic environment within the penumbra. Without
      therapeutic intervention, many cells within the penumbra will die and become part
      of the growing infarct, however, there is hope that appropriate therapies may
      allow potential recovery of cells within this tissue region, or at least slow the
      rate of cell death, therefore, slowing the spread of the ischemic infarct and
      minimizing the extent of tissue damage. As such, preserving the penumbra to
      promote functional brain recovery is a central goal in stroke research. While
      identification of the ischemic infarct, and the infarct/penumbra boundary is
      relatively trivial using classical histology and microscopy techniques,
      accurately assessing the penetration of the penumbra zone into undamaged brain
      tissue, and evaluating the magnitude of chemical alterations in the penumbra, has
      long been a major challenge to the stroke research field. In this study, we have
      used synchrotron-based X-ray fluorescence imaging to visualize the elemental
      changes in undamaged, penumbra, and infarct brain tissue, following ischemic
      stroke. We have employed a Gaussian mixture model to cluster tissue areas based
      on their elemental characteristics. The method separates the core of the infarct
      from healthy tissue, and also demarcates discrete regions encircling the infarct.
      These regions of interest can be combined with elemental and metabolic data, as
      well as with conventional histology. The cell populations defined by clustering
      provide a reproducible means of visualizing the size and extent of the penumbra
      at the level of the single cell and provide a critically needed tool to track
      changes in elemental status and penumbra size.

PMID- 29370524
TI  - l-Carnitine Inhibits Lipopolysaccharide-Induced Nitric Oxide Production of SIM-A9
      Microglia Cells.
AB  - Microglia are the resident immune effector cells of the central nervous system.
      They account for approximately 10-15% of all cells found in the brain and spinal
      cord, acting as macrophages, sensing and engaging in phagocytosis to eliminate
      toxic proteins. Microglia are dynamic and can change their morphology in response
      to cues from their milieu. Parkinson's disease is a neurodegenerative disease,
      associated with reactive gliosis, neuroinflammation, and oxidative stress. It is
      thought that Parkinson's disease is caused by the accumulation of abnormally
      folded alpha-synuclein protein, accompanied by persistent neuroinflammation,
      oxidative stress, and subsequent neuronal injury/death. There is evidence in the
      literature for mitochondrial dysfunction in Parkinson's disease as well as fatty
      acid beta-oxidation, involving l-carnitine. Here we investigate l-carnitine in
      the context of microglial activation, suggesting a potential new strategy of
      supplementation for PD patients. Preliminary results from our studies suggest
      that the treatment of activated microglia with the endogenous antioxidant l
      carnitine can reverse the effects of detrimental neuroinflammation in vitro.

PMID- 29370525
TI  - Tungsten Disulfide-Gold Nanohole Hybrid Metasurfaces for Nonlinear Metalenses in
      the Visible Region.
AB  - Recently, nonlinear hybrid metasurface comes into an attractive new concept in
      the research of nanophotonics and nanotechnology. It is composed of
      semiconductors with an intrinsically large nonlinear susceptibility and
      traditional plasmonic metasurfaces, offering opportunities for efficiently
      generating and manipulating nonlinear optical responses. A high second-harmonic
      generation (SHG) conversion efficiency has been demonstrated in the mid-infrared
      region by using multiquantum-well (MQW)-based plasmonic metasurfaces. However, it
      has yet to be demonstrated in the visible region. Here, we present a new type of
      nonlinear hybrid metasurfaces for the visible region, which consists of a single
      layer of tungsten disulfide (WS2) and a phased gold nanohole array. The results
      indicate that a large SHG susceptibility of ~10-1 nm/V at 810 nm is achieved,
      which is 2-3 orders of magnitude larger than that of typical plasmonic
      metasurfaces. Nonlinear metalenses with the focal lengths of 30, 50, and 100 MUm
      are demonstrated experimentally, providing a direct evidence for both generating
      and manipulating SH signals based on the nonlinear hybrid metasurfaces. It shows
      great potential applications in designing of integrated, ultrathin, compacted,
      and efficient nonlinear optical devices, such as frequency converters, nonlinear
      holography, and the generation of nonlinear optical vortex beams.

PMID- 29370527
TI  - Iodometry-Assisted Liquid Chromatography Electrospray Ionization Mass
      Spectrometry for Analysis of Organic Peroxides: An Application to Atmospheric
      Secondary Organic Aerosol.
AB  - Organic peroxides comprise a significant fraction of atmospheric secondary
      organic aerosol (SOA). Detection and quantification of particle-phase organic
      peroxides are highly challenging, and current efforts rely significantly on
      filter extraction and offline mass spectrometry (MS). Here, a novel technique,
      iodometry-assisted liquid chromatography electrospray ionization mass
      spectrometry (iodometry-assisted LC-ESI-MS), is developed and evaluated with a
      class of atmospherically relevant organic peroxides, alpha-acyloxyalkyl
      hydroperoxides, synthesized via liquid ozonolysis. Iodometry-assisted LC-ESI-MS
      unambiguously distinguishes organic peroxides, compensating for the lack of
      functional group information that can be obtained with MS. This technique can be
      versatile for a wide spectrum of environmental analytical applications for which
      a molecular-level identification of organic peroxide is required. Here, iodometry
      assisted LC-ESI-MS is applied to the water-soluble organic carbon (WSOC) of alpha
      pinene SOA. Unexpectedly, a limited number of detectable compounds in WSOC appear
      to be organic peroxides, despite the fact that spectroscopy-based iodometry
      indicates 15% of WSOC mass is associated with organic peroxides. This observation
      would be consistent with decomposition of multifunctional organic peroxides to
      small peroxides that can be quantified by spectroscopy-based iodometry but not by
      LC-ESI-MS. Overall, this study raises concerns regarding filter extraction-based
      studies, showing that assignment of organic peroxides solely on the basis of MS
      signatures can be misleading.

PMID- 29370526
TI  - Nanoparticle-Mediated Trapping of Wnt Family Member 5A in Tumor Microenvironments
      Enhances Immunotherapy for B-Raf Proto-Oncogene Mutant Melanoma.
AB  - Development of an effective treatment against advanced tumors remains a major
      challenge for cancer immunotherapy. Approximately 50% of human melanoma is driven
      by B-Raf proto-oncogene mutation (BRAF mutant). Tumors with such mutation are
      desmoplastic, highly immunosuppressive, and often resistant to immune checkpoint
      therapies. We have shown that immunotherapy mediated by low-dose doxorubicin
      induced immunogenic cell death was only partially effective for this type of
      tumor and not effective in long-term inhibition of tumor progression. Wnt family
      member 5A (Wnt5a), a signaling protein highly produced by BRAF mutant melanoma
      cells, has been implicated in inducing dendritic cell tolerance and tumor
      fibrosis, thus hindering effective antigen presentation and T-cell infiltration.
      We hypothesized that Wnt5a is a key molecule controlling the immunosuppressive
      tumor microenvironment in metastatic melanoma. Accordingly, we have designed and
      generated a trimeric trap protein, containing the extracellular domain of Fizzled
      7 receptor that binds Wnt5a with a Kd ~ 278 nM. Plasmid DNA encoding for the
      Wnt5a trap was delivered to the tumor by using cationic lipid-protamine-DNA
      nanoparticles. Expression of Wnt5a trap in the tumor, although transient, was
      greater than that of any other major organs including liver, resulting in a
      significant reduction of the Wnt5a level in the tumor microenvironment without
      systematic toxicity. Significantly, combination of Wnt5a trapping and low-dose
      doxorubicin showed great tumor growth inhibition and host survival prolongation.
      Our findings indicated that efficient local Wnt5a trapping significantly
      remodeled the immunosuppressive tumor microenvironment to facilitate immunogenic
      cell-death-mediated immunotherapy.

PMID- 29370528
TI  - Daily cycle in hepatic lipid metabolism in obese mice, Neotomodon alstoni: Sex
      differences.
AB  - Disruption of circadian rhythms influences the pathogenesis of obesity,
      particularly with the basic regulation of food intake and metabolism. A link
      between metabolism and the circadian clock is the peroxisome proliferator
      activated receptors (PPARs). The Neotomodon alstoni mouse, known as the "Mexican
      volcano mouse," may develop obesity if fed a normo-caloric diet. This manuscript
      documents the changes in part of the hepatic lipid homeostasis in both sexes of
      lean and obese N. alstoni mice, comparing the daily changes in the BMAL1 clock
      protein, in regulators of lipid metabolism (PGC-1alpha, PPARalpha-gamma, SREBP
      1c, and CPT-1alpha) and in free fatty acid (FFA) and hepatic triacylglyceride
      (TAG) metabolites in light-dark cycles. Hepatic tissue and blood were collected
      at 5, 10, 15, 19, and 24 h. Samples were analyzed by western blotting to
      determine the relative presence of protein. The results indicate that obesity
      affects daily changes in lipid metabolism and the BMAL1 profile in females
      considerably more than in males. These results suggest that the impact of obesity
      on lipid metabolism has important differences according to sex.

PMID- 29370529
TI  - Temporal expression of clock genes in central and peripheral tissues of spotted
      munia under varying light conditions: Evidence for circadian regulation of daily
      physiology in a non-photoperiodic circannual songbird species.
AB  - We investigated if the duration and/or frequency of the light period affect 24-h
      rhythm of circadian clock genes in central and peripheral tissues of a non
      photoperiodic songbird, the spotted munia (Lonchura punctulata), in which a
      circannual rhythm regulates the reproductive cycle. We monitored activity-rest
      pattern and measured 24-h mRNA oscillation of core clock (Bmal1, Clock, Per2,
      Cry1 and Cry2) and clock-controlled (E4bp4, Roralpha and Rev-erbalpha) genes in
      the hypothalamus, retina, liver and gut of spotted munia subjected to an aberrant
      light-dark (LD) cycle (3.5L:3.5D; T7, T = period length of LD cycle) and
      continuous light (LL, 24L:0D), with controls on 24-h LD cycle (T24, 12L:12D).
      Munia exhibited rhythmic activity-rest pattern with period matched to T7 or T24
      under an LD cycle and were arrhythmic with a scattered activity pattern and
      higher activity duration under LL. At the transcriptional level, both clock and
      clock-controlled genes showed a significant 24-h rhythm in all four tissues
      (except Clock in the liver) under 12L:12D, suggesting a conserved tissue-level
      circadian time generation in spotted munia. An exposure to 3.5L:3.5D or LL
      induced arrhythmicity in transcriptional oscillation of all eight genes in the
      hypothalamus (except Rev-erbalpha) and liver (except Bmal1 and Rev-erbalpha under
      T7 and Cry1 under LL). In the retina, however, all genes showed arrhythmic 24-h
      mRNA expression under LL, but not under T7 (except in E4bp4 and Roralpha).
      Interestingly, unlike in the liver, Bmal1, Per2, Cry1, Roralpha and Rev-erbalpha
      mRNA expressions were rhythmic in the gut under both T7 (except Roralpha) and LL
      conditions. These results showed variable relationship of internal circadian
      clocks with the external light environment and suggested a weak coupling of
      circadian clocks between the central (hypothalamus and retina) and peripheral
      (liver and gut) tissues. We suggest tissue-level circadian clock regulation of
      daily physiology and behavior in the spotted munia.

PMID- 29370530
TI  - Head First, Not Feet First: Freeman-Sheldon Syndrome as Primarily a Craniofacial
      Condition.
AB  - The historical and clinical basis for classification of Freeman-Sheldon syndrome
      as a craniofacial syndrome and explanation of the rationale underlying this
      decision is provided. Correctly classifying the condition will avoid confusion
      and may help to clarify the vernacular employed and eventually aid in improving
      diagnosis.

PMID- 29370531
TI  - Evaluation of the plant-growth-promoting abilities of endophytic bacteria from
      the psammophyte Ammodendron bifolium.
AB  - The objective of this study was to assess the plant-growth-promoting abilities of
      45 endophytic bacterial isolates from Ammodendron bifolium through physiological
      characteristics detection and endophytic bacteria-plant interaction. Each of
      these isolates exhibited 1 or more plant-growth-promoting traits, but only 11
      isolates belonging to the genera Bacillus, Staphylococcus, and Kocuria were
      capable of promoting seed germination and radicle growth. These results together
      with the results of the correlation analysis revealed that the completion of seed
      germination may not be due to IAA production, phosphate solubilization, pellicle
      formation, and ACC deaminase, protease and lipase production by endophytic
      bacteria, but may be closely related to amylase and cellulase production.
      Further, endophytic bacterial isolates with plant-growth-promoting traits may
      also provide beneficial effects to host plants at different growth stages. Thus,
      these results are of value for understanding the ecological roles of endophytic
      bacteria in host plant habitats and can serve as a foundation for further studies
      of their potential in plant regeneration.

PMID- 29370536
TI  - Traumatic brain injury: classification, models, and markers.
AB  - Traumatic brain injury (TBI) is a leading cause of morbidity and mortality
      worldwide. Due to its high incidence rate and often long-term sequelae, TBI
      contributes significantly to increasing costs of health care expenditures
      annually. Unfortunately, advances in the field have been stifled by patient and
      injury heterogeneity that pose a major challenge in TBI prevention, diagnosis,
      and treatment. In this review, we briefly discuss the causes of TBI, followed by
      its prevalence, classification, and pathophysiology. The current imaging
      detection methods and animal models used to study brain injury are examined. We
      discuss the potential use of molecular markers in detecting and monitoring the
      progression of TBI, with particular emphasis on microRNAs as a novel class of
      molecular modulators of injury and its repair in the neural tissue.

PMID- 29370537
TI  - The Use of Chromatographic Methods Coupled to Mass Spectrometry for the Study of
      Emerging Pollutants in the Environment.
AB  - The consumption of compounds that improve the human health and wellness is
      increasing, and as a result, the residues of these substances reach the
      environment or food chain. For this reason, the scientific community is looking
      for new analytical methods that are more accurate and can detect the greatest
      number of compounds in different matrices. This manuscript compares different
      studies in abiotic and biotic matrices, where most of them (92%) uses Liquid
      Chromatography to separate the compounds. For the detection, most of the studies
      for both matrices uses, coupled to the chromatograph, a triple quadrupole mass
      spectrometer (50%) due to the precision to quantify the concentration of these
      compounds. Time of Flight (QToF) mass spectrometer is used in 24% of the
      manuscripts reviewed, in both matrices. It is possible to quantify the
      concentration of these compounds with the instrument but do not provide as high
      accuracy as the triple quadrupole.

PMID- 29370538
TI  - Exploring longitudinal course and treatment-baseline severity interactions in
      secondary outcomes of smoking cessation treatment in individuals with attention
      deficit hyperactivity disorder.
AB  - BACKGROUND: A double blind, placebo-controlled randomized trial (NCT00253747)
      evaluating osmotic-release oral system methylphenidate (OROS-MPH) for smoking
      cessation revealed a significant interaction effect in which participants with
      higher baseline ADHD severity had better abstinence outcomes with OROS-MPH while
      participants with lower baseline ADHD severity had worse outcomes. OBJECTIVES:
      This current report examines secondary outcomes that might bear on the mechanism
      for this differential treatment effect. METHODS: Longitudinal analyses were
      conducted to evaluate the effect of OROS-MPH on three secondary outcomes (ADHD
      symptom severity, nicotine craving, and withdrawal) in the total sample (N = 255,
      56% Male), and in the high (N = 134) and low (N = 121) baseline ADHD severity
      groups. RESULTS: OROS-MPH significantly improved ADHD symptoms and nicotine
      withdrawal symptoms in the total sample, and exploratory analyses showed that in
      both higher and lower baseline severity groups, OROS-MPH statistically
      significantly improved these two outcomes. No effect on craving overall was
      detected, though exploratory analyses showed statistically significantly
      decreased craving in the high ADHD severity participants on OROS-MPH. No
      treatment by ADHD baseline severity interaction was detected for the outcomes.
      CONCLUSIONS: Methylphenidate improved secondary outcomes during smoking cessation
      independent of baseline ADHD severity, with no evident treatment-baseline
      severity interaction. Our results suggest divergent responses to smoking
      cessation treatment in the higher and lower severity groups cannot be explained
      by concordant divergence in craving, withdrawal and ADHD symptom severity, and
      alternative hypotheses may need to be identified.

PMID- 29370535
TI  - Effects of prenatal alcohol exposure (PAE): insights into FASD using mouse models
      of PAE.
AB  - The potential impact of prenatal alcohol exposure (PAE) varies considerably among
      exposed individuals, with some displaying serious alcohol-related effects and
      many others showing few or no overt signs of fetal alcohol spectrum disorder
      (FASD). In animal models, variables such as nutrition, genetic background,
      health, other drugs, and stress, as well as dosage, duration, and gestational
      timing of exposure to alcohol can all be controlled in a way that is not possible
      in a clinical situation. In this review we examine mouse models of PAE and focus
      on those with demonstrated craniofacial malformations, abnormal brain
      development, or behavioral phenotypes that may be considered FASD-like outcomes.
      Analysis of these data should provide a valuable tool for researchers wishing to
      choose the PAE model best suited to their research questions or to investigate
      established PAE models for FASD comorbidities. It should also allow recognition
      of patterns linking gestational timing, dosage, and duration of PAE, such as
      recognizing that binge alcohol exposure(s) during early gestation can lead to
      severe FASD outcomes. Identified patterns could be particularly insightful and
      lead to a better understanding of the molecular mechanisms underlying FASD.

PMID- 29370540
TI  - Industrial potential of carotenoid pigments from microalgae: Current trends and
      future prospects.
AB  - Microalgae are rich source of various bioactive molecules such as carotenoids,
      lipids, fatty acids, hydrocarbons, proteins, carbohydrates, amino acids, etc. and
      in recent Years carotenoids from algae gained commercial recognition in the
      global market for food and cosmeceutical applications. However, the production of
      carotenoids from algae is not yet fully cost effective to compete with synthetic
      ones. In this context the present review examines the technologies/methods in
      relation to mass production of algae, cell harvesting for extraction of
      carotenoids, optimizing extraction methods etc. Research studies from different
      microalgal species such as Spirulina platensis, Haematococcus pluvialis,
      Dunaliella salina, Chlorella sps., Nannochloropsis sps., Scenedesmus sps.,
      Chlorococcum sps., Botryococcus braunii and Diatoms in relation to carotenoid
      content, chemical structure, extraction and processing of carotenoids are
      discussed. Further these carotenoid pigments, are useful in various health
      applications and their use in food, feed, nutraceutical, pharmaceutical and
      cosmeceutical industries was briefly touched upon. The commercial value of algal
      carotenoids has also been discussed in this review. Possible recommendations for
      future research studies are proposed.

PMID- 29370539
TI  - Correlates of employment and postsecondary education enrolment in Afghanistan and
      Iraq veterans with traumatic brain injuries.
AB  - PRIMARY OBJECTIVE: About 20% of Iraq and Afghanistan Veterans have sustained a
      traumatic brain injury (TBI), which can result in postconcussive symptoms and
      difficulty transitioning from the military to civilian employment and
      postsecondary education. To better inform programs help Veterans transition back
      into civilian life, we evaluated correlates of employment and postsecondary
      education enrolment among treatment-seeking Veterans with a history of TBI.
      RESEARCH DESIGN: A cross-sectional design, using an archival database of VA
      medical records, was used to answer these research questions. METHODS AND
      PROCEDURES: We examined demographic, TBI-related, postconcussive, psychiatric,
      and neuropsychological factors in 390 Veterans (86% with mild TBI) to determine
      what factors were associated with employment or enrolment in postsecondary
      education. Bivariate correlations and multivariate regression were used. MAIN
      OUTCOMES AND RESULTS: age, minority status, and service connected disability
      ratings were significantly associated with employment and postsecondary education
      enrolment in a multivariate context, whereas TBI-related factors and
      neurocognitive, postconcussive, and psychiatric symptom severity were not
      associated with employment or postsecondary education outcomes. CONCLUSIONS:
      Further research is needed to confirm these findings and to evaluate the
      contribution of age, minority status, and disability on successful return to work
      and/or school for Veterans with a history of TBI.

PMID- 29370541
TI  - Effects of lunar phases on short-term, explosive physical performance among young
      trained athletes.
AB  - Beliefs that lunar phases affect human physiology started in ancient times.
      Research has recently revealed that a physical fitness index increased in
      sedentary students at the new moon (NM) and full moon (FM) compared to other moon
      phases. However, the effect of lunar cycle (moon illumination and gravitational
      pull) on physical performance in athletes was not examined. Therefore, this study
      aimed to evaluate whether short-term explosive performance can be influenced by
      the different phases of the lunar cycle. Fourteen young male Taekwondo athletes
      (age: 16.9 +/- 0.7 years, height: 159.7 +/- 50.6 cm, body mass: 62.85 +/- 7.84
      kg) performed the following tests to assess the explosive physical performance
      during the different phases of the lunar cycle (NM, FQ (first quarter), FM, and
      LQ (last quarter)): maximal isometric manual contraction (dominant hand (MIMCD)
      and non-dominant hand (MIMCND)), maximal back isometric contraction (MBIC), squat
      jump (SJ), countermovement jump (CMJ), and 10-m sprint (10 m). The testing
      sessions during the different moon phases were performed in a counterbalanced
      order. The order of tests remained the same (MIMCD, MIMCND, MBIC, SJ, CMJ, and 10
      m), and all sessions were performed in the evening (6:00 to 8:00 p.m.) on the
      first day of each evaluated lunar phase. Each parameter was measured over two
      consecutive lunar months in the calendar. Analysis of variance tests showed that
      there was no significant effect of lunar cycle on all explosive test measures, p
      > 0.05. Our results failed to identify any effect of lunar phase on evening
      explosive performance (mainly involving phosphagen pathway-based efforts) among
      young trained athletes. Therefore, it appears that moon phase/illumination does
      not affect short-term physical performance in young trained adolescents.

PMID- 29370543
TI  - Driving under the influence of alcohol and drugs in the eastern part of Denmark
      in 2015 and 2016: Abuse patterns and trends.
AB  - OBJECTIVES: The objective of this study was to examine the frequency of
      psychoactive drugs and alcohol in drivers under suspicion of driving under the
      influence of drugs and alcohol in 2015 and 2016 in the eastern part of Denmark.
      The trends in the number of traffic cases sent for drug analysis since 2000 and
      alcohol analysis since 2011 are also discussed. METHODS: Blood samples from
      drivers suspected of being under the influence of alcohol and/or medication
      and/or illicit drugs in 2015 and 2016 were investigated as requested by the
      police. The blood samples were screened for alcohol and/or tetrahydrocannabinol
      (THC) alone, for other drugs (covering all drugs, except THC, listed in the
      Danish list of narcotic drugs), or for THC and other drugs. Age and gender were
      also recorded. The number of drug traffic cases since 2000 and the number of
      alcohol cases since 2011 were extracted from our Laboratory Information
      Management System (LIMS). RESULTS: In total, 11,493 traffic cases were
      investigated. Alcohol and/or drugs exceeded the legal limit in 9,657 (84%) cases.
      Men constituted 95% of the drivers investigated for drugs and 88% of the alcohol
      cases. The drivers investigated for drugs consisted primarily of young men,
      whereas drivers investigated for alcohol were older. The frequency was higher for
      positive alcohol cases above the legal limit (87%) than for drug cases (76%)
      above the fixed concentration limit. THC (67-69%) was the most frequently
      detected drug above the legal limit, followed by cocaine (27-28.5%), amphetamine
      (17%), and clonazepam (6-7%) in both years. Morphine (5.4%), included among the 5
      most frequent drugs in 2015, was replaced by methadone (4.6%) in 2016. Few new
      psychoactive drugs (NPS) were detected. The number of traffic cases sent for drug
      analysis has increased more than 30-fold since 2000-2006, and the number of
      traffic cases submitted in 2016 for drug analysis was higher than the number for
      alcohol analysis; the latter has decreased since 2011. CONCLUSION: Overall,
      alcohol was the most frequent compound detected above the legal limit in both
      years, followed by the well-known illicit drugs THC, cocaine, and amphetamine.
      NPS were seldom seen. One consequence of the increased focus on drugs in traffic
      has been an immense increase in drug traffic cases sent for analysis since 2006
      in the eastern part of Denmark. Although this survey revealed only minimal
      changes compared to earlier investigations, surveys like this are invaluable for
      monitoring abuse patterns and trends in drugged and drunken driving.

PMID- 29370542
TI  - Capacity of ceruloplasmin to scavenge products of the respiratory burst of
      neutrophils is not altered by the products of reactions catalyzed by
      myeloperoxidase.
AB  - CP is a copper-containing ferroxidase of blood plasma, which acts as an acute
      phase reactant during inflammation. The effect of oxidative modification of CP
      induced by oxidants produced by MPO, such as HOCl, HOBr, and HOSCN, on its
      spectral, enzymatic, and anti-inflammatory properties was studied. We monitored
      the chemiluminescence of lucigenin and luminol along with fluorescence of
      hydroethidine and scopoletin to assay the inhibition by CP of the neutrophilic
      respiratory burst induced by PMA or fMLP. Superoxide dismutase activity of CP and
      its capacity to reduce the production of oxidants in respiratory burst of
      neutrophils remained virtually unchanged upon modifications caused by HOCl, HOBr,
      and HOSCN. Meanwhile, the absorption of type I copper ions at 610 nm became
      reduced, along with a drop in the ferroxidase and amino oxidase activities of CP.
      Likewise, its inhibitory effect on the halogenating activity of MPO was
      diminished. Sera of either healthy donors or patients with Wilson disease were co
      incubated with neutrophils from healthy volunteers. In these experiments, we
      observed an inverse relationship between the content of CP in sera and the rate
      of H2O2 production by activated neutrophils. In conclusion, CP is likely to play
      a role of an anti-inflammatory factor tempering the neutrophil respiratory burst
      in the bloodstream despite the MPO-mediated oxidative modifications.

PMID- 29370544
TI  - Evaluation Criteria and Surgical Technique for Transoral Access to the Thyroid
      Gland: Experimental Study.
AB  - BACKGROUND: The development of endoscopic techniques motivated surgeons to search
      for alternative and more cosmetic approaches for thyroid and parathyroid surgery.
      Several variations of transoral access to the anterior neck areas were applied in
      recent years. One of them is a premandibular access proposed by Nakajo et al, it
      is performed through the oral vestibule by creating the working space by means of
      the lifting method. MATERIALS AND METHODS: Nineteen unfixed human cadavers were
      used to develop the endoscopic access to the thyroid gland and surgical
      techniques of its resection. The Nakajo access was modified by altering the
      spatial location of the working instruments, resulting in practically no impact
      on the cosmetic outcome but providing a more comfortable operation for the
      thyroid gland. We determined evaluation criteria of the cadaver model before
      initiation of the experimental trial. Parameters that influence on alteration of
      these criteria were registered. RESULTS: Of the 19 operated objects, the first 7
      were used to practice the access technique from the incision in the oral
      vestibule to the thyroid gland in order to evaluate the possibility of endoscopic
      dissection of the important anatomical. The next 12 surgeries were carried out by
      manipulating the thyroid gland in the settings maximally close to real. Access
      implied good cosmetic results, less surgical traumatic due to a smaller area of
      detachment of the musculocutaneous flap. CONCLUSIONS: The achieved results show
      feasibility of introducing the described modification of transoral thyroidectomy
      into clinical practice.

PMID- 29370545
TI  - A Study of the Use of Psychopharmacologic Agents by Acutely Medically Ill Older
      Adults.
AB  - This retrospective study sought to investigate issues related to the safety of
      psychopharmacological agents used by acutely medically ill hospitalized older
      adults. It explored if there were any associations between commonly prescribed
      psychiatric medications that medically ill hospitalized older adults received and
      adverse events. It also sought to compare the safety of antidepressants,
      sedative/hypnotics, and antipsychotics, when used as a standing (on a preset
      schedule) and as needed pro re nata (PRN) basis. The study found that
      psychopharmacological agents are frequently prescribed for medically ill
      hospitalized older adults. No statistically significant difference was found as
      far as safety was concerned. The number of PRN medications that were used, and
      the total number of medications was associated with increased risk of transfer
      within the hospital to a higher level of care or transfer upon discharge to long
      term-care/rehabilitation or hospice. Overall, the use of psychopharmacological
      agents did not appear to be related to serious adverse events.

PMID- 29370546
TI  - An Environmental Scan of the Role of Nurses in Preventing Fetal Alcohol Spectrum
      Disorders.
AB  - Nurses are in an ideal position to talk to their patients of reproductive age
      about alcohol use and encourage the prevention of alcohol-exposed pregnancies.
      Effective conversations can be efficiently included in the clinical encounter to
      identify alcohol misuse and offer appropriate follow-up. This report presents
      results of an environmental scan of resources relevant to nursing professionals
      and nurses' role in addressing alcohol misuse. Gaps in nursing education and
      practice guidelines with regard to defining the nursing role in preventing
      alcohol-exposed pregnancies were revealed. Findings identified a need to promote
      adoption among nurses of evidence-based preventive practices to prevent alcohol
      misuse.

PMID- 29370547
TI  - Depressive Symptoms and Influencing Factors in Low-Risk Mothers.
AB  - INTRODUCTION: Depressive symptoms burden not only postpartum women, but can also
      compromise partner relationships and mother-infant interactions. With
      approximately 15% of women affected by perinatal mood and anxiety disorders
      (PMADs) each year, maternity care providers must be sensitive to personal
      characteristics and complaints that influence women's potential to develop
      postpartum depression (PPD). The purpose of the study was to identify personal
      characteristics and modifiable factors associated with depressive symptoms in low
      risk postpartum women. METHODS: A descriptive, correlational design was used to
      identify predictors of depressive symptoms among mothers who were considered to
      be at low risk for PPD. Self-report data related to mood, stress, sleep
      disturbance, and fatigue were collected near the sixth week post-delivery from
      women (N = 62) in a southern US state. RESULTS: The levels of stress and reports
      of sleep disturbance approached clinical concern in the low-risk sample (n = 62),
      in addition to being positively correlated depressive symptoms. Cesarean delivery
      was also associated with increased depressive symptoms and predictive of
      depression symptoms when combined with perceived chronic stress, sleep
      disturbance, and fatigue. DISCUSSION: The findings underscore the importance of
      assessing maternal mental health and adjustment during the postpartum period.
      While some mothers may not report depressive symptoms at post-delivery visits,
      they may be experiencing symptoms that predispose them to a mood disorder. Using
      a more holistic approach to postpartum care, with concern for both physical and
      mental well-being, may be a necessary shift to promote health in new mothers and
      families.

PMID- 29370548
TI  - American Values, Social Policy, Health and Well-Being.

PMID- 29370549
TI  - The Formation of a Community Academic Partnership to Address Health Disparities
      and Improve Outcomes for Latino Family Caregivers Living in a Rural Community.

PMID- 29370550
TI  - The Transition from University Completion to Employment for Students with Autism
      Spectrum Disorder.
AB  - A scoping review of articles published from 2000 to 2017 was conducted with the
      aim to identify what had been discussed and researched related to the transition
      from completion of university to employment for students with ASD. The review
      also included identification of published data on the type of degrees studied by
      university students with ASD. A paucity of discussion and no specific research
      was identified related to the aims of the review.

PMID- 29370551
TI  - Tumor Biological Aspects of a Large-Scale Retrospective Study: The Role of Tumor
      Cell Heterogeneity, Inflammation and Aging in Survival.

PMID- 29370552
TI  - The Role of the Registered Nurse Working in Substance Use Disorder Treatment: A
      Hermeneutic Study.
AB  - Substance Use Disorders (SUDs) are a national public health crisis. However,
      there is minimal existing research literature on the role of the nurse working in
      SUD treatment. The purpose of this study was to describe the meaning of the
      professional role of the registered nurse working in the SUD setting. The study
      utilized a Heideggerian Phenomenological approach with a modified Colaizzi method
      for analysis and interpretation. The nine study participants, two males and seven
      females, aged 27-60 had worked in SUD treatment for 1-37 years. Three major
      themes, with sub-themes, emerged: Defining the Role for Self; Learning the Role;
      and Navigating with Ease in an Unchangeable Culture. Findings demonstrated that
      nurses in SUD treatment value their role and the care of patients with SUDs.
      Patient recovery or relapse influenced job satisfaction. Significantly, the
      findings highlighted an outdated role with rigid boundaries and no real
      contemporary identity. Findings can be used to address the need for a
      contemporary SUD nursing identity and to support ongoing involvement of nurses in
      health policy related to SUDs.

PMID- 29370553
TI  - Wu-Wei: Concept Analysis of a Conceptual Paradox.
AB  - The Taoist concept of wu-wei is explored through a concept analysis, as
      delineated by Walker and Avant. The paradoxical nature of wu-wei is explored
      through different uses, defining attributes, a model case, related and
      illegitimate cases, antecedents and consequences, and empirical referents.
      Practical applications for mental health nursing assessment and interventions are
      offered to show potential improved outcomes with the stance of wu-wei in
      practice. Wu-wei arises in the emptying of the vessel (oneself) of ego, thus
      allowing more skillful, adaptable, collaborative mental health nursing in the
      moment.

PMID- 29370554
TI  - Assessing Intimate Partner Abuse: Associated Factors and Health Consequences
      among Jordanian Women.
AB  - In this cross-sectional study, we assessed levels and types of psychological and
      physical intimate partner abuse (IPA), and the association of IPA with socio
      demographic factors and health consequences. The Abusive Behavior Inventory was
      completed by 471 Jordanian women. IPA was higher among older women who were: of
      older age, of younger age at marriage, married to unemployed spouses, living in
      urban residence, and of lower educational level. IPA was associated with most of
      the health problems except dental injuries and burns. We recommend educational
      programs that raise women's awareness to their rights to education, free choices
      in marital age, and policies that mitigate IPA in Jordan and similar patriarchal
      societies.

PMID- 29370555
TI  - The Effectiveness of Cognitive Behavioral Therapy versus Psychoeducation in the
      Management of Depression among Patients Undergoing Haemodialysis.
AB  - The aim of this randomized controlled trial was to compare the effectiveness of
      psychoeducation versus cognitive behavioral therapy (CBT) in the management of
      depression among renal dialysis patients. A sample of 130 dialysis patients
      participated in the study and they were assigned at random to one of two
      therapies: psychoeducation (N = 65) or CBT (N = 65). Hamilton depression rating
      scale was completed by the participants in both groups prior to the therapies and
      after completion. Both therapies were effective in the management of depression,
      although psychoeducation was superior. Psychoeducation is recommended over CBT in
      the management of depression among renal dialysis patients.

PMID- 29370556
TI  - Multiple Evanescent White Dot Syndrome Following Intradermal Influenza
      Vaccination.
AB  - PURPOSE: To present a case report of MEWDS following an intradermal influenza
      vaccination. METHODS: Review of the clinical, laboratory, photographic, and
      angiographic records of a patient with MEWDS. RESULTS: 27-year-old female that
      presented to our clinic with photopsias OD. These symptoms began 2 weeks
      following an influenza intradermal vaccination. Fundus examination and diagnostic
      testing were consistent with MEWDS. CONCLUSION: While rare, MEWDS can occur
      following influenza vaccination.

PMID- 29370557
TI  - Patient- and caregiver-identified preferences: Dimensions of change in
      developmental therapy treatment goals.
AB  - OBJECTIVE: To describe patterns in preferred dimensions of change in therapy
      goals identified by individuals with developmental disability and their
      caregivers. METHODS: A retrospective chart review of Goal Attainment Scaling
      (GAS) goals for patients aged 2-32 years (n = 124) participating in a program of
      episodic care was conducted. Dimensions of change were analyzed through a mixed
      methods study design. Co-occurrence rates and descriptor-to-code comparisons were
      computed in order to relate the dimension of change to diagnosis, International
      Classification of Functioning, Disability, and Health (ICF) goal domain, gender,
      age, and goal setter. RESULTS: Decreased level of assistance was the most
      commonly identified preferred dimension of change, cited in 31.0% of goals.
      Decreased level of assistance remained the most frequently reported dimension of
      change in multiple subgroup analyses. CONCLUSION: Independence is highly valued
      by parents and individuals with developmental disability. This finding should
      help guide therapy plans or program development addressing task performance.

PMID- 29370559
TI  - Resilience in Caregivers of Partners With Young Onset Dementia: A Concept
      Analysis.
AB  - INTRODUCTION: Over 200,000 Americans diagnosed with young onset dementia (YOD),
      dementia diagnosed prior to age 65, are cared for by family members. This can be
      costly to caregivers' physical and psychological health. Some adapt well to the
      caregiver role and are said to be resilient. Aim/Question: This paper builds on
      current understanding of the concept of resilience and applies this to caregivers
      of partners diagnosed with YOD. METHOD: Concept analysis. RESULTS: Resilient
      caregivers exhibit attributes including determination, flexibility, positive
      thinking, self-efficacy, resourcefulness, social support and spirituality.
      DISCUSSION: YOD affects caregiver's health. Much research has been done on
      interventions for dementia caregivers. These interventions do not necessarily
      meet the needs of YOD caregivers as they do not account for dynamics in the
      family. By recognizing what is resiliency in YOD caregivers, interventions can be
      developed that focus on characteristics that build these attributes. IMPLICATIONS
      FOR PRACTICE: Understanding the concept of resilience related to caregiving for a
      partner diagnosed with YOD allows for future development, measurement, and
      evaluation of nursing interventions. Nursing staff are in a strategic position to
      provide effective interventions to enhance resilience among caregivers of YOD.

PMID- 29370558
TI  - Pim-3 enhances melanoma cell migration and invasion by promoting STAT3
      phosphorylation.
AB  - Melanoma is the deadliest form of commonly encountered skin cancer, and has fast
      propagating and highly invasive characteristics. Pim-3, a highly expressed
      oncogene in melanoma, is a highly conserved serine/threonine kinase with various
      biological activities, such as proliferation-accelerating and anti-apoptosis
      effects on cancer progression. However, whether Pim-3 regulates melanoma
      metastasis has not been determined. Here, we constructed a Pim-3-silencing short
      hairpin RNA (sh-Pim-3), a TLR7-stimulating ssRNA and a dual-function vector
      containing a sh-Pim-3 and a ssRNA, and transfected them into the B16F10 melanoma
      cell line to investigate the effects of Pim-3 on migration and invasion in
      melanoma. We found that sh-Pim-3 inhibited B16F10 cell migration and invasion in
      vitro. In a tumor-bearing mouse model, sh-Pim-3 significantly downregulated
      pulmonary metastasis of B16F10 melanoma cell in vivo. Mechanistically, sh-Pim-3
      inhibited metastasis by regulating the expression of genes related to epithelial
      mesenchymal transition (EMT). Further study revealed that by promoting the
      phosphorylation of STAT3 (signal transducer and activator of transcription 3),
      Pim-3 induced the expression of Slug, Snail, and ZEB1, which enhanced EMT-related
      changes and induced melanoma migration and invasion. Our study suggests that Pim
      3 is a potential effective target for melanoma therapy.

PMID- 29370560
TI  - Unique Practice, Unique Place: Exploring Two Assertive Community Treatment Teams
      in Maine.
AB  - Assertive Community Treatment (ACT) is a model of care that provides
      comprehensive community-based psychiatric care for persons with serious mental
      illness. This model has been widely documented and has shown to be an evidence
      based model of care for reducing hospitalizations for this targeted population.
      Critical ingredients of the ACT model are the holistic nature of their services,
      a team based approach to treatment and nurses who assist with illness management,
      medication monitoring, and provider collaboration. Although the model remains
      strong there are clear differences between urban and rural teams. This article
      describes present day practice in two disparate ACT programs in urban and rural
      Maine. It offers a new perspective on the evolving and innovative program of
      services that treat those with serious mental illness along with a review of
      literature pertinent to the ACT model and future recommendations for nursing
      practice. The success and longevity of these two ACT programs are testament to
      the quality of care and commitment of staff that work with seriously mentally ill
      consumers. Integrative care models such as these community-based treatment teams
      and nursing driven interventions are prime elements of this successful model.

PMID- 29370561
TI  - Nursing Case Management Strategies for Adults with Serious Mental Illness Seeking
      Dental Services.
AB  - A university-community partnership initiated a dental screening and nursing case
      management program for Medicaid-insured adults with serious mental illness (SMI).
      Forty-three adults with SMI participated in dental screening; 72% participated in
      case management. Per client, an average of six case management contacts was made.
      After 6 months, 87% (27/31) had attended at least one dental appointment, with a
      13% no-show rate; 8 completed treatment, 4 had ongoing treatment, 12 had
      interrupted care, and 3 were lost to follow-up. Adults with SMI experienced high
      unmet dental needs; nursing case management strategies aided clients to initiate
      and complete dental care.

PMID- 29370562
TI  - "This is not a Life Anyone would want"-A Qualitative Study of Norwegian ACT
      Service users' Experience with Mental Health Treatment.
AB  - We discuss Norwegian service users' experiences with community mental health
      treatment in general, and the interprofessional Assertive Community Treatment
      (ACT) model in particular. To gain the right to treatment, service users have to
      accept certain limitations, such as medication and community treatment orders
      (CTOs). Seventy participants responded to five open-ended questions. In addition,
      eight of them participated in either focus group or interviews. A collaborative
      approach, using Stepwise-Deductive Induction (SDI) method was used to analyze the
      participants' experiences. The results showed that the treatment contributes to
      an experience of autonomy but also one of restriction. It provides service users
      with enhanced normalcy, but simultaneously a feeling of deviance. There needs to
      be an ongoing reflection and discussion about those paradoxes in treatment, and
      service users have to be involved.

PMID- 29370563
TI  - Depression, Quality of Life, Physical Activity, and the Impact of Drugs on Sexual
      Activity in a Population-Based Sample, Ages 20-59 Years.
AB  - Sexual quality of life is important for many individuals; therefore, this study
      examined the frequency of depression in a younger and middle-aged population
      based sample, and the impact on physical activity, quality of life, and sexual
      activity, and the role of antidepressant and cardiac drugs on sexual function.
      The sample, ages 20 to 59 years, completed relevant items for depression, sexual
      activity, physical activity, quality of life, and drugs. Data were analyzed using
      descriptive statistics, Pearson correlations, t-tests, and analysis of variance.
      Those sexually active had lower mean depression scores and higher ratings of
      quality of life, while those sexually inactive had greater depression and took
      more drugs. Thorough assessment of drugs, depression, cardiac and other medical
      conditions, and interest and engagement in sexual activity should be routinely
      assessed in all patients, regardless of age.

PMID- 29370564
TI  - Epidemic Retinitis.
AB  - PURPOSE: To study demography, seasonal variation, clinical presentation, and
      treatment outcome of "retinitis post febrile illness." (RpFI) Method: Case
      records of patients diagnosed as RpFI, from July 2009 to May 2017 were studied
      retrospectively. Patients with complete follow up were evaluated for treatment
      and visual outcomes. RESULTS: Two hundred and five eyes of 119 patients were
      studied. The peak incidence of RpFI was from November to March each year.
      Diagnosis of fever largely remained unknown. Chikungunya IgM, Dengue IgM, and
      Weil-Felix test was positive in 22.22%, 15.38%, and 39.75%, respectively, in
      investigated cases. The mean visual acuity at presentation and at resolution was
      20/63 and 20/32, respectively, in 122 eyes with complete follow up. CONCLUSION:
      We suggest a term "Epidemic Retinitis" for RpFI due to its seasonal variation and
      to differentiate it from other sporadic forms of retinitis. Although RpFI has
      aggressive presentation, it resolves over 3-4 months and the overall visual
      outcome is satisfactory.

PMID- 29370565
TI  - Clinical Profile of Scleritis in Children.
AB  - PURPOSE: To describe the clinical pattern of scleritis in patients <=16 years of
      age at a tertiary care eye hospital in India. METHODS: The medical records of 24
      eyes of 20 children with scleritis were included in this retrospective study.
      Collected data included age, subsets of uveitis, best corrected visual acuities
      (BCVA), detailed laboratory investigations and treatment. RESULTS: Mean age at
      presentation was 12.2 +/- 2.5 years. Scleritis was unilateral in 80% patients and
      an equal gender distribution was observed. Posterior scleritis (41.7%) was the
      most common subtypes of scleritis and nodular scleritis was the most common type
      of anterior scleritis (33.3%). Necrotizing scleritis was seen in 16.7% eyes.
      Tuberculosis was the only systemic association and found in three (15%) patients.
      CONCLUSIONS: Clinical profile of scleritis in children can be different from that
      of adults.

PMID- 29370566
TI  - Total Corneal Melt in Patient with Porphyria Cutanea Tarda in Presence of another
      Risk Factor.
AB  - PURPOSE: To report a case of two siblings affected by porphyria cutanea tarda
      (PCT) presenting with varying severity of ocular disease and evaluation of
      difference in the presence of risk factors. METHODS: Case report Result: A 42
      year-old Indian male diagnosed with PCT and history of daily intake of alcohol,
      presented with sudden decrease in vision of right eye. Examination showed
      perforated cornea surrounded by rim of 360-degree avascular necrotic sclera, with
      no evidence of infection. Similar systemic history was present in his elder
      brother. He did not consume alcohol and presented with mere localized scleral
      thinning. Since the patient's sibling acted as a natural control for the
      evaluation of alcohol as an independent risk factor, the difference in severity
      of disease can be explained on the basis of difference in alcohol intake.
      CONCLUSION: In the presence of progression of the disease, other risk factors
      like intake of alcohol should be evaluated.

PMID- 29370567
TI  - Complications in Intermediate Uveitis: Prevalence, Time of Onset, and Effects on
      Vision in Short-Term and Long-Term Follow-Up.
AB  - PURPOSE: To study the prevalence and time of onset of ocular complications in
      intermediate uveitis (IU) and to assess their effects on visual outcome in short
      term and long-term follow-up. METHODS: A retrospective cohort study of patients
      with IU who had a minimal follow-up of one year. RESULTS: 96 patients (174 eyes,
      70% females) were included with a mean age at presentation of 30 years. Children
      constituted 38% of all patients. Mean follow- up was 64.9 months. Pars planitis
      was the most common form followed by sarcoidosis and multiple sclerosis. Cystoid
      macular edema (CME), cataract, epiretinal membrane and posterior synechiae were
      the most prevalent complications. Posterior synechiae, band keratopathy, cataract
      and papillitis at presentation were associated with worse presenting visual
      acuity (VA). Of the late-onset complications, glaucoma/ocular hypertension (OHT)
      was the most significantly associated with worse long-term VA. Most sight
      threatening complications (namely CME and glaucoma) were diagnosed at
      presentation while late complications predominantly affected the posterior
      segment and included among others peripheral retinal elevations,
      vasoproliferative tumors, and vitreous hemorrhage. Median LogMAR VA improved at
      short-term and long-term follow-up, from 0.2 to 0.1 (p<0.001). Subgroup analysis
      revealed significant VA improvement for eyes with all the different complications
      except for eyes with glaucoma/OHT. CONCLUSION: IU is a chronic low-grade uveitis
      that may be associated with protean early and late complications of the anterior
      or posterior segments or both. Optimal treatment regimens are imperative for the
      strict control of inflammation and proper management of complications thus
      allowing a favorable long-term prognosis.

PMID- 29370568
TI  - The Experiences of Older Adults with Dual Diagnosis in an Inner Melbourne
      Community Mental Health Service.
AB  - Less is known about the experiences of older adults (65+ years of age) with co
      occurring mental health and alcohol and other drug use disorders (dual diagnosis)
      than is known about the experiences of their younger counterparts. This
      exploratory qualitative study sought to interview individuals receiving case
      management from an inner Melbourne community mental health service to determine
      their experiences of living with dual diagnosis and explore their interactions
      with mental health and addiction treatment, and general medical services alike.
      Six older adults with a dual mental health and substance disorder agreed to
      participate in a semi-structured interview process and provided their
      perspectives about living with complex mental illness and alcohol and other drug
      use. Several key themes emerged throughout the interview process, mirroring the
      notion of dual diagnosis being a complex phenomenon involving a number of
      interrelated factors: these include medical complexity, poor service engagement
      and long-term use of alcohol and other drugs. Interviews also demonstrate the
      challenges inherent in providing care to this cohort, with the participants
      frequently describing their experiences with services as being fraught with
      difficulty. The increased understanding of the perspectives of older adults with
      dual diagnosis provides the foundation for further research into this population
      in addition to influencing future nursing care provided to this cohort.

PMID- 29370569
TI  - Redactions in protocols for drug trials: what industry sponsors concealed.
AB  - Objective To describe the redactions in contemporary protocols for industry
      sponsored randomised drug trials with patient relevant outcomes and to evaluate
      whether there was a legitimate rationale for the redactions. Design Cohort study.
      Under the Freedom of Information Act, we requested access to trial protocols
      approved by a research ethics committee in Denmark from October 2012 to March
      2013. We received 17 consecutive protocols, which had been redacted before we got
      them, and nine protocols without redactions. In five additional cases, the
      companies refused to let the committees give us access, and in three other cases,
      documents were missing. Participants Not applicable. Setting Not applicable. Main
      outcome measure Amount and nature of redactions in 22 predefined key protocol
      variables. Results The redactions were most widespread in those sections of the
      protocol where there is empirical evidence of substantial problems with the
      trustworthiness of published drug trials: data analysis, handling of missing
      data, detection and analysis of adverse events, definition of the outcomes,
      interim analyses and premature termination of the study, sponsor's access to
      incoming data while the study is running, ownership to the data and
      investigators' publication rights. The parts of the text that were redacted
      differed widely, both between companies and within the same company. Conclusions
      We could not identify any legitimate rationale for the redactions. The current
      mistrust in industry-sponsored drug trials can only change if the industry offers
      unconditional access to its trial protocols and other relevant documents and
      data.

PMID- 29370571
TI  - An Intraocular Inflammatory Profile of Rubella Associated Uveitis.
AB  - PURPOSE: To analyze intraocular cytokine levels and cell profiles in patients
      with rubella virus-associated uveitis (RVU). METHODS: We collected intraocular
      fluid samples from patients with RVU (n = 10), uveitis of other causes (n = 27),
      and cataract (n = 22). Levels of 15 cytokines (IL-1beta, IL-1ra, IL-2, IL-6, IL
      6ralpha, IL-7, IL-8, IL-10, IL-17A, IL-23, TARC, MCP-1, TNF-alpha, PlGF, and
      VEGF) were measured using multiplex assay, and intraocular cell populations were
      determined by multiparameter flowcytometry. Clinical characteristics of RVU
      patients were collected and compared to laboratory outcomes. RESULTS: RVU
      patients exhibited high intraocular levels of MCP-1, IL-6ralpha, and TARC, whilst
      patients with noninfectious uveitis were characterized by high levels of PlGF.
      Cataract patients showed high levels of IL-2 and IL-23. Intraocular cell
      population of RVU patients disclosed mainly T-cells and monocytes/macrophages and
      B-cells were scarcely detected. CONCLUSION: RVU patients exhibit a cytokine
      profile distinct from noninfectious uveitis and cataract.

PMID- 29370570
TI  - PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through
      PIK3R3/NF-kB/TP pathway.
AB  - Phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) is overexpressed in
      different types of human cancer. We previously reported the important role of
      PIK3R3 in colorectal cancer (CRC). However, the prognosis effect of PIK3R3 in CRC
      is still remaining unclear. In this study, we explored online clinical databases
      to analyze the prognosis differences between higher and lower expression of
      PIK3R3 in CRC patients. Interestingly, we found that better disease-free survival
      (DFS) were occurred in patients with higher expression of PIK3R3, but there is no
      significant difference in overall survival (OS). For further, we showed that
      PIK3R3 could enhance 5-FU induced apoptosis by regulating the expression of
      thymmidine phosphorylase (TP). In conclusion, PIK3R3 could be considered as a
      predictor of 5-FU sensitivity for personalized treatment, and a therapeutic
      target for colorectal cancer.

PMID- 29370572
TI  - Use of Gevokizumab in Patients with Behcet's Disease Uveitis: An International,
      Randomized, Double-Masked, Placebo-Controlled Study and Open-Label Extension
      Study.
AB  - PURPOSE: The purpose of this article is to demonstrate the superiority of
      gevokizumab as compared to placebo, on top of current standard of care, in
      reducing the risk of Behcet's disease uveitis (BDU) exacerbations. METHODS:
      Randomized, double-masked, placebo-controlled, parallel group, event-driven trial
      in BDU patients having recently experienced an ocular exacerbation, subsequently
      undergoing a tapering procedure from high-dose corticosteroids and receiving 60
      mg gevokizumab or placebo every 4 weeks subcutaneously (EYEGUARD B
      ClinicalTrials.gov NCT 01965145). RESULTS: A total of 83 patients (40
      gevokizumab, 43 placebo) were included. Gevokizumab did not significantly affect
      the risk of occurrence of ocular exacerbations. However, data suggested that
      gevokizumab could preserve visual acuity, reduce the uveitis severity, decrease
      the emergence of macular edema, and have a corticosteroid sparing effect.
      Gevokizumab was well tolerated. CONCLUSIONS: While the primary efficacy endpoint
      was not met with gevokizumab, the control of IL-1beta pathway in patients with
      BDU may still be a relevant target.

PMID- 29370573
TI  - A crosstalk between extracellular ATP and jasmonate signaling pathways for plant
      defense.
AB  - Damage-associated molecular patterns (DAMPs), such as extracellular ATP, act as
      danger signals in response to biotic and abiotic stresses. Extracellular ATP is
      perceived by a plant purinoceptor, P2 receptor kinase 1 (P2K1), inducing
      downstream signaling for defense responses. How ATP induces these defense
      responses has not been well studied. A recent study by Tripathi et al. (Plant
      Physiology, 176: 511-523, 2018) revealed a synergistic interaction between
      extracellular ATP and jasmonate (JA) signaling during plant defense responses.
      This signaling crosstalk requires the formation of secondary messengers, i.e.,
      cytosolic calcium, reactive oxygen species, and nitric oxide. This finding has
      given a new direction towards understanding the defense signals activated by
      DAMPs. In this addendum, we discuss possible insights into how extracellular ATP
      signaling interacts with the JA signaling pathway for plant defense responses.

PMID- 29370574
TI  - The protective effect of ticagrelor on renal function in a mouse model of sepsis
      induced acute kidney injury.
AB  - Platelets are traditionally considered to be essential components of primary
      hemostasis. Recent investigations have revealed that platelets can be activated
      in patients with sepsis and are implicated in the development of sepsis and
      sepsis-induced-acute kidney injury (SAKI). In the present study, ticagrelor was
      used to induce a mouse model of SAKI by cecal ligation and puncture. It was found
      that ticagrelor could inhibit platelet activity, decrease the levels of
      interleukin-1beta and serum creatinine, reduce infiltration of neutrophils in
      renal tissue, and attenuate cell apoptosis in the kidney. The results suggested
      that ticagrelor could protect renal function by inhibiting inflammation,
      recruitment of neutrophils into the kidney, and cell apoptosis in renal tissue.
      Thus, the findings might provide new strategies for preventing SAKI.

PMID- 29370575
TI  - Nanoparticle concentrations and composition in a dental office and dental
      laboratory: A pilot study on the influence of working procedures.
AB  - During material treatment in dentistry particles of different size are released
      in the air. To examine the degree of particle exposure, air scanning to dental
      employees was performed by the Scanning Mobility Particle Sizer. The size, shape
      and chemical composition of particles collected with a low-pressure impactor were
      determined by scanning electronic microscopy and X-ray dispersive analysis. The
      average concentrations of nanoparticles during working periods in a clean dental
      laboratory (45,000-56,000 particles/cm3), in an unclean dental laboratory (28,000
      74,000 particles/cm3), and in a dental office (21,000-50,000 particles/cm3), were
      significantly higher compared to average concentrations during nonworking periods
      in the clean dental laboratory (11,000-24,000 particles/cm3), unclean laboratory
      (14,000-40,000 particles/cm3), and dental office (13,000-26,000 particles/cm3).
      Peak concentration of nanoparticles in work-intensive periods were found
      significantly higher (up to 773,000 particles/cm3), compared to the non-working
      periods (147,000 particles/cm3) and work-less intensive periods (365,000
      particles/cm3). The highest mass concentration value ranged from 0.055-0.166
      mg/m3. X-ray dispersive analysis confirmed the presence of carbon, potassium,
      oxygen, iron, aluminum, zinc, silicon, and phosphorus as integral elements of
      dental restorative materials in form of nanoparticle clusters, all smaller than
      100 nm. We concluded that dental employees are exposed to nanoparticles in their
      working environment and are therefore potentially at risk for certain respiratory
      and systematic diseases.

PMID- 29370576
TI  - Circumscription and phylogeny of the Lepidostromatales (lichenized Basidiomycota)
      following discovery of new species from China and Africa.
AB  - Based on an exhaustive sampling of all known Lepidostromatales, a lineage of
      clavarioid lichen-forming basidiomycetes, we assess (i) the phylogenetic
      affinities of the six Chinese species currently accommodated in Multiclavula
      (Cantharellales) based on inferences from the 18S and 28S subunits of the nuclear
      ribosomal DNA repeat and (ii) the phylogenetic structure among Chinese
      populations of Lepidostromatales, based on the nuc rDNA ITS1-5.8S-ITS2 (internal
      transcribed spacer [ITS]) regions. Multiclavula fossicola and M. sinensis belong
      to the Lepidostromatales and are transferred to Sulzbacheromyces. Chinese reports
      of M. clara and M. vernalis belong to species of Lepidostromatales, and specimens
      identified as M. mucida belong to the nonlichenized genus Clavaria. Hence,
      evidence of Multiclavula occurring in China is lacking. Similarly, L. calocerum
      is excluded from the Chinese flora. The recently described L. asianum should be
      regarded as conspecific with S. sinensis. Three new species of Sulzbacheromyces
      are described: S. bicolor and S. yunnanensis from China and S. miomboensis from
      the Democratic Republic of Congo. Consequently, Sulzbacheromyces is new to Asia
      and Africa. A worldwide key to the species of Lepidostromatales is provided.

PMID- 29370578
TI  - Microbial hazards during harvesting and processing at an outdoor United States
      cannabis farm.
AB  - Cannabis cultivation is an emerging industry within the United States. Organic
      dust derived in part from naturally occurring microorganisms is known to cause
      byssinosis in the hemp industry. In this pilot study, bacteria and fungi
      encountered by workers at an outdoor cannabis farm that utilized organic
      practices were elucidated by 16 S ribosomal RNA (rRNA) and Internal Transcribed
      Spacer (ITS) region sequencing, respectively. Area (n = 14) and personal air
      samples (n = 12) were collected during harvesting and processing activities. 16 S
      rRNA and ITS regions of extracted bacterial and fungal genomic DNA were amplified
      and sequenced using Sanger sequencing. Bacterial sequencing resolved 1,077
      sequences that were clustered into 639 operational taxonomic units (OTUs) and
      predominantly placed in the phylum, Actinobacteria (46%). Personal air samples
      revealed higher bacterial and Actinobacteria diversity compared to outdoor area
      samples collected within the facility (p < 0.05). A high degree of dissimilarity
      between bacteria was identified within and between samples. Fungal sequences (n =
      985) were identified and predominantly clustered in the phylum Ascomycota (53%).
      Of the 216 fungal OTUs elucidated, the cannabis plant pathogenic species,
      Botrytis cinerea, was the most prevalent and accounted for 34% of all fungal
      sequences. The relative abundance of B. cinerea was highest in personal air
      samples (59%) compared to area samples collected in the drying room (19%),
      greenhouse (18%), and outdoor environment (6%). There was 49% sample similarity
      between fungi identified within personal air samples, but higher dissimilarity
      coefficients were observed within and between greenhouse, drying room, and
      outdoor area air samples. The results of this pilot study suggest that the
      cannabis farm workers are potentially exposed to Actinobacteria as well as the
      cannabis plant pathogen, B. cinerea during harvesting, bud-stripping, and hand
      trimming processes.

PMID- 29370577
TI  - Maternal-fetal transmission of the zika virus: An intriguing interplay.
AB  - In this review, we give an overview of aspects related to the congenital
      transmission of the Zika virus (ZIKV). Although we acknowledge that important
      advances in research on ZIKV pathogenesis have come from studies using animal
      models, particularly non-human primates, this review emphasizes studies using ex
      vivo human cells and tissues as well as natural infections in pregnant women. The
      possible routes used by ZIKV to cross or breach the placental barrier and infect
      the fetal central nervous system are presented. Understanding the viral infection
      biology and ZIKV pathogenesis during pregnancy may guide the design of affordable
      antiviral strategies to benefit pregnant women in areas at risk.

PMID- 29370580
TI  - Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection.

PMID- 29370579
TI  - Epichloe hybrida, sp. nov., an emerging model system for investigating fungal
      allopolyploidy.
AB  - Endophytes of the genus Epichloe (Clavicipitaceae, Ascomycota) frequently occur
      within cool-season grasses and form interactions with their hosts that range from
      mutualistic to antagonistic. Many Epichloe species have arisen via interspecific
      hybridization, resulting in species with two or three subgenomes that retain all
      or nearly all of their original parental genomes, a process termed
      allopolyploidization. Here, we characterize Epichloe hybrida, sp. nov., a
      mutualistic species that has increasingly become a model system for investigating
      allopolyploidy in fungi. The Epichloe species so far identified as the closest
      known relatives of the two progenitors of E. hybrida are E. festucae var. lolii
      and E. typhina. We confirm that the nuclear genome of E. hybrida contains two
      homeologs of most protein-coding genes from E. festucae and E. typhina, with
      genome-wide gene expression analysis indicating a slight bias in overall gene
      expression from the E. typhina subgenome. Mitochondrial DNA is detectable only
      from E. festucae, whereas ribosomal DNA is detectable only from E. typhina.
      Inheriting ribosomal DNA from just one parent might be expected to preferentially
      favor interactions with ribosomal proteins from the same parent, but we find that
      ribosomal protein genes from both parental subgenomes are nearly all expressed
      equally in E. hybrida. Finally, we provide a comprehensive set of resources for
      this model system that are intended to facilitate further study of fungal
      hybridization by other researchers.

PMID- 29370581
TI  - The effects of two assistive technologies on reading comprehension accuracy and
      rate.
AB  - This study compared the effectiveness of two assistive technologies to
      accommodate the word reading skills of four middle school students with reading
      learning disabilities. Kurzweil 3000 is a continuous text-to-speech (TTS)
      computer software program that allows students to follow along on a computer
      monitor while passages are read aloud. A reading pen is a discontinuous TTS
      assistive technology (AT) device that allows students to scan and hear selected
      words read aloud. An adapted alternating treatments design was implemented to
      compare the effects of listening-while-reading using continuous TTS AT,
      discontinuous TTS AT, and silently reading without accommodation on reading
      comprehension accuracy and rate. Results indicate that in three of the four
      participants, continuous TTS technology led to the greatest improvements in both
      comprehension accuracy and rate when compared to silent reading with effect sizes
      reaching 0.70 and 0.99, respectively. The fourth participant demonstrated the
      highest comprehension accuracy and rate in the discontinuous TTS condition. The
      discontinuous TTS condition led to the lowest comprehension rates across all four
      students. Additionally, participants generally found the continuous TTS AT to be
      the more acceptable of the two accommodations. Discussion focuses on possible
      theoretical explanations for the results and implications for future research.

PMID- 29370582
TI  - First report of the post-fire morel Morchella exuberans in eastern North America.
AB  - Reports of true morels (Morchella) fruiting on conifer burn sites are common in
      western North America where five different fire-adapted species of black morels
      (Elata Clade) have been documented based on multilocus phylogenetic analyses.
      Fruiting of post-fire morels in eastern North America, by comparison, are rare
      and limited to a report from Minnesota in 1977 and eastern Ontario in 1991. Here,
      nuc rDNA internal transcribed spacer (ITS1-5.8S-ITS2 = ITS) sequences were used
      to identify the post-fire morel that fruited in great abundance the year
      following the 2012 Duck Lake Fire in the Upper Peninsula of Michigan and after
      the 2016 large-scale fire in the Great Smoky Mountains National Park in Tennessee
      as M. exuberans. A preliminary phylogenetic analysis suggests that the
      collections from eastern North America may be more closely related to those from
      Europe than from western North America, Europe, and China.

PMID- 29370583
TI  - Immune gene expression and response to chemotherapy in advanced breast cancer.
AB  - BACKGROUND: Transcriptomic profiles have shown promise as predictors of response
      to neoadjuvant chemotherapy in breast cancer (BC). This study aimed to explore
      their predictive value in the advanced BC (ABC) setting. METHODS: In a Phase 3
      trial of first-line chemotherapy in ABC, a fine needle aspiration biopsy (FNAB)
      was obtained at baseline. Intrinsic molecular subtypes and gene modules related
      to immune response, proliferation, oestrogen receptor (ER) signalling and
      recurring genetic alterations were analysed for association with objective
      response to chemotherapy. Gene-set enrichment analysis (GSEA) of responders vs
      non-responders was performed independently. Lymphocytes were enumerated in FNAB
      smears and the absolute abundance of immune cell types was calculated using the
      Microenvironment Cell Populations counter method. RESULTS: Gene expression data
      were available for 109 patients. Objective response to chemotherapy was
      statistically significantly associated with an immune module score (odds ratio
      (OR)=1.62; 95% confidence interval (CI), 1.03-2.64; P=0.04). Subgroup analysis
      showed that this association was restricted to patients with ER-positive or
      luminal tumours (OR=3.54; 95%, 1.43-10.86; P=0.012 and P for interaction=0.04).
      Gene-set enrichment analysis confirmed that in these subgroups, immune-related
      gene sets were enriched in responders. CONCLUSIONS: Immune-related
      transcriptional signatures may predict response to chemotherapy in ER-positive
      and luminal ABC.

PMID- 29370584
TI  - The size, morphology, site, and access score predicts critical outcomes of
      endoscopic mucosal resection in the colon.
AB  - BACKGROUND:  The SMSA (size, morphology, site, access) polyp scoring system is a
      method of stratifying the difficulty of polypectomy through assessment of four
      domains. The aim of this study was to evaluate the ability of SMSA to predict
      critical outcomes of endoscopic mucosal resection (EMR). METHODS:  We
      retrospectively applied SMSA to a prospectively collected multicenter database of
      large colonic laterally spreading lesions (LSLs) >= 20 mm referred for EMR.
      Standard inject-and-resect EMR procedures were performed. The primary end points
      were correlation of SMSA level with technical success, adverse events, and
      endoscopic recurrence. RESULTS:  2675 lesions in 2675 patients (52.6 % male)
      underwent EMR. Failed single-session EMR occurred in 124 LSLs (4.6 %) and was
      predicted by the SMSA score (P < 0.001). Intraprocedural and clinically
      significant postendoscopic bleeding was significantly less common for SMSA 2 LSLs
      (odds ratio [OR] 0.36, P < 0.001 and OR 0.23, P < 0.01) and SMSA 3 LSLs (OR 0.41,
      P  < 0.001 and OR 0.60, P = 0.05) compared with SMSA 4 lesions. Similarly,
      endoscopic recurrence at first surveillance was less likely among SMSA 2 (OR
      0.19, P < 0.001) and SMSA 3 (OR 0.33, P < 0.001) lesions compared with SMSA 4
      lesions. This also extended to second surveillance among SMSA 4 LSLs. CONCLUSION:
      SMSA is a simple, readily applicable, clinical score that identifies a subgroup
      of patients who are at increased risk of failed EMR, adverse events, and adenoma
      recurrence at surveillance colonoscopy. This information may be useful for
      improving informed consent, planning endoscopy lists, and developing quality
      control measures for practitioners of EMR, with potential implications for EMR
      benchmarking and training.

PMID- 29370585
TI  - Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium
      pannonicum.
AB  - Tripolinolate A as a new bioactive phenolic ester was previously isolated from a
      halophyte of Tripolium pannonicum. However, the in vitro and in vivo anti-glioma
      effects and mechanism of tripolinolate A have not been investigated. This study
      has demonstrated that (1) tripolinolate A inhibited the proliferation of
      different glioma cells with IC50 values of 7.97 to 14.02 uM and had a significant
      inhibitory effect on the glioma growth in U87MG xenograft nude mice, (2)
      tripolinolate A induced apoptosis in glioma cells by downregulating the
      expressions of antiapoptotic proteins and arrested glioma cell cycle at the G2/M
      phase by reducing the expression levels of cell cycle regulators, and (3)
      tripolinolate A also remarkably reduced the expression levels of several glioma
      metabolic enzymes and transcription factors. All data together suggested that
      tripolinolate A had significant in vitro and in vivo anti-glioma effects and the
      regulation of multiple tumor-related regulators and transcription factors might
      be responsible for the activities of tripolinolate A against glioma.

PMID- 29370586
TI  - [Vertebral Body Height after Balloon Kyphoplasty vs. Radiofrequency Kyphoplasty].
AB  - BACKGROUND: Kyphoplasty is used to alleviate pain and to restore the initial
      height of osteoporotic vertebral fractures (OVF). One of the most recent
      procedures is radiofrequency-targeted vertebral augmentation (RFTVA). We
      investigated whether restoration with this method is similar and as adequate as
      with the established procedure of balloon kyphoplasty (BKP), as assessed by the
      anatomical height of the vertebral body. The aim of our study was to compare the
      intravertebral angles (base-endplate) post- and preoperatively with these two
      procedures. PATIENTS AND METHODS: The base and endplate angles were measured on
      142 vertebral bodies treated by kyphoplasty (67 BKP and 75 RFTVA), on the basis
      of pre- and postoperative X-rays in the upright position in 87 volunteers (46 BKP
      and 41 RFTVA). The main object was to detect the degree of correction (Deltapost
      preop) with BKP compared to RFTVA. Furthermore, the sagittal alignment of the
      adjacent heathy levels were measured. RESULTS: Significant correction was
      detected with both BKP (BKPpre: 11.5 +/- 6.0 degrees , BKPpost: 6.2 +/- 4.6
      degrees , p < 0.001) and RFTVA (RFTVApre: 9.9 +/- 6.2 degrees , RFTVApost: 6.3 +/
      4.4 degrees , p < 0.001). Potential correction was greater with BKP than with
      RFTVA (Deltapost-pre BKP: - 5.3 +/- 4.4 degrees , Deltapost-pre RFK: - 3.6 +/-
      4.4 degrees , p = 0.03). Neither procedures gave a significant change in the
      sagittal angle in the adjacent segment (segment BKPpre: 13.8 +/- 8.0 degrees ,
      Segment BKPpost: 12.5 +/- 9,2 degrees , p = 0.638; Segment RFTVApre: 18,8 +/-
      14,3 degrees , Segment RFTVApost: 15.0 +/- 13.2 degrees , p = 0.330). CONCLUSION:
      BKP gave significantly better correction, even though both methods were able to
      restore significant improvement in the kyphotic angle. In the adjacent levels,
      correction of the sagittal angle was not significant, although the influence of
      the intervention on alignment tended to be less.

PMID- 29370587
TI  - [The impact of the androgen receptor splice variant AR-V7 on the prognosis and
      treatment of advanced prostate cancer].
AB  - A recently discovered mechanism enabling prostate cancer cells to escape the
      effects of endocrine therapies consists in the synthesis of C-terminally
      truncated, constitutively active androgen receptor (AR) splice variants (AR-V).
      Devoid of a functional C-terminal hormone/ligand binding domain, various AR-Vs
      are insensitive to therapies targeting the androgen/AR signalling axis.
      Preliminary studies suggest that AR-V7, the most common AR-V, is a promising
      predictive tumour marker and a relevant selection marker for the treatment of
      advanced prostate cancer. This review critically outlines recent advances in AR
      V7 diagnostics and presents an overview of current AR-V7 targeted therapies.

PMID- 29370589
TI  - Optimal management of radial artery grafts in CABG: Patient and target vessel
      selection and anti-spasm therapy.
AB  - The current literature on radial artery grafting is reviewed focusing on the
      optimal deployment of radial artery grafts in coronary artery bypass surgery with
      specific attention to the selection of patients and target vessels for radial
      artery grafting.

PMID- 29370588
TI  - Asymptomatic non-occlusive thrombosis of the aortic root.

PMID- 29370590
TI  - HSR Begins a New Era.

PMID- 29370593
TI  - Re: AlliumTM TPS-A New Prostatic Stent for the Treatment of Patients with Benign
      Prostatic Obstruction: The First Report.

PMID- 29370592
TI  - Re: Hypovitaminosis D is Associated with Lower Urinary Tract Symptoms and Benign
      Prostate Hyperplasia in Type 2 Diabetes.

PMID- 29370591
TI  - Trends in Gallbladder Cancer Incidence and Survival in Korea.
AB  - PURPOSE: The current study was undertaken to examine the trend in gallbladder
      cancer (GBC) incidence and survival in Korea. Materials and Methods: GBC
      incidence data by histologic typewere obtained from the Korea Central Cancer
      Registry. Age-standardized incidence rates were calculated using the mid-year
      Korean population of 2000 as a standard population, and a joinpoint regression
      model was used to calculate the annual percent change (APC) in incidence rates.
      Incidence by Surveillance, Epidemiology and End results (SEER) summary stage and
      by geographical areas and female-to-male incidence rate ratios was also
      described. RESULTS: The number of new GBC cases increased between 1999 and 2013.
      Nevertheless, the agestandardized incidence rate decreased by 0.5% per year in
      men (p < 0.01), whereas the incidence rate in women did not change significantly
      over the same period (APC, -0.2; p=0.6). The most common histologic type was
      adenocarcinoma in both sexes. Based on the SEER stage, the distant stage was the
      most frequent stage (41%), followed by the regional stage (37%). Ulsan
      (4.31/100,000 for men and 4.09/100,000 forwomen in 2009- 2013) and Gyeongsangnam
      do (4.15/100,000 for men and 3.54/100,000 for women) showed the highest GBC
      incidence, whereas the lowest incidence was observed in Seoul and Gyeonggi-do.
      There were no significant sex differences in the incidence of GBC (femaleto-male
      incidence rate ratio, 0.96). CONCLUSION: The overall incidence of GBC in Korea
      did not change significantly over the 15-year period. Incidence for men and women
      was similar. However, geographical variation was found.

PMID- 29370594
TI  - Re: Bee Venom Suppresses Testosterone-Induced Benign Prostatic Hyperplasia by
      Regulating the Inflammatory Response and Apoptosis.

PMID- 29370595
TI  - Re: Public Perceptions of Overlapping Surgery.

PMID- 29370596
TI  - Re: Operating Room Fires and Surgical Skin Preparation.

PMID- 29370597
TI  - Re: Sex on the Brain! Associations between Sexual Activity and Cognitive Function
      in Older Age.

PMID- 29370598
TI  - Re: The Use of Portable Video Media vs Standard Verbal Communication in the
      Urological Consent Process: A Multicentre, Randomised Controlled, Crossover
      Trial.

PMID- 29370599
TI  - Re: Sexual Health and Positive Subjective Well-Being in Partnered Older Men and
      Women.

PMID- 29370600
TI  - Re: Prevalence of Positive Screening Test for Cognitive Impairment among Elderly
      Urogynecologic Patients.

PMID- 29370601
TI  - Re: Frailty and Post-Operative Outcomes in Older Surgical Patients: A Systematic
      Review.

PMID- 29370602
TI  - Re: Anesthesia Exposure and Risk of Dementia and Alzheimer's Disease: A
      Prospective Study.

PMID- 29370603
TI  - Re: Complications and Quality of Life in Elderly Patients with Several
      Comorbidities Undergoing Cutaneous Ureterostomy with Single Stoma or Ileal
      Conduit after Radical Cystectomy.

PMID- 29370604
TI  - Re: Understanding the Use of Prostate Biopsy among Men with Limited Life
      Expectancy in a Statewide Quality Improvement Collaborative.

PMID- 29370606
TI  - Re: Bacterial Resistance in Urinary Tract Infections in Patients with Diabetes
      Matched with Patients without Diabetes.

PMID- 29370605
TI  - Re: Small (< 4 cm) Renal Tumors with Predominantly Low Signal Intensity on T2
      Weighted Images: Differentiation of Minimal-Fat Angiomyolipoma from Renal Cell
      Carcinoma.

PMID- 29370607
TI  - Re: Prospective Randomized Trial Comparing Titanium Clips to Bipolar Coagulation
      in Sealing Lymphatic Vessels during Pelvic Lymph Node Dissection at the Time of
      Robot-Assisted Radical Prostatectomy.

PMID- 29370608
TI  - Re: Safety and Early Oncologic Effectiveness of Primary Robotic Retroperitoneal
      Lymph Node Dissection for Nonseminomatous Germ Cell Testicular Cancer.

PMID- 29370609
TI  - Re: Sexual Function after Cervical Spine Surgery: Independent Predictors of
      Functional Impairment.

PMID- 29370611
TI  - Re: Female Sexual Dysfunction (FSD): Prevalence and Impact on Quality of Life
      (QoL).

PMID- 29370610
TI  - Re: Hypoactive Sexual Desire Dysfunction in Community-Dwelling Older Women.

PMID- 29370612
TI  - Re: Relationship between Age and Erectile Dysfunction Diagnosis or Treatment
      Using Real-World Observational Data in the USA.

PMID- 29370613
TI  - Re: Hypoactive Sexual Desire Disorder: International Society for the Study of
      Women's Sexual Health (ISSWSH) Expert Consensus Panel Review.

PMID- 29370614
TI  - Re: Association between Treatment for Erectile Dysfunction and Death or
      Cardiovascular Outcomes after Myocardial Infarction.

PMID- 29370615
TI  - Re: Subclinical Vascular Disease and Subsequent Erectile Dysfunction: The
      Multiethnic Study of Atherosclerosis (MESA).

PMID- 29370616
TI  - Re: Men's Sexual Response to Female Partner's Intranasal Oxytocin Administration
      for Hypoactive Sexual Desire Disorder: An Open Prospective Cohort Study.

PMID- 29370617
TI  - Re: Validity of Premature Ejaculation Diagnostic Tool and its Association with
      International Index of Erectile Function-15 in Chinese Men with Evidence-Based
      Defined Premature Ejaculation.

PMID- 29370618
TI  - Re: p-Values and Reproductive Health: What Can Clinical Researchers Learn from
      the American Statistical Association?

PMID- 29370619
TI  - Re: Combination of Mesenchymal Stem Cell Injection with Icariin for the Treatment
      of Diabetes-Associated Erectile Dysfunction.

PMID- 29370620
TI  - Re: Clinical Decision-Making in Azoospermic Men: In Search of the Ideal
      Prediction Model.

PMID- 29370622
TI  - Re: Analysis of Semen Parameters during 2 Weeks of Daily Ejaculation: A First in
      Humans Study.

PMID- 29370623
TI  - Re: Prediction Model for Live Birth in ICSI Using Testicular Extracted Sperm.

PMID- 29370621
TI  - Re: Prediction Model for Obtaining Spermatozoa with Testicular Sperm Extraction
      in Men with Non-Obstructive Azoospermia.

PMID- 29370624
TI  - Re: Moderate Aerobic Exercise Training for Improving Reproductive Function in
      Infertile Patients: A Randomized Controlled Trial.

PMID- 29370625
TI  - Re: Men's Knowledge of Their Own Fertility: A Population-Based Survey Examining
      the Awareness of Factors that are Associated with Male Infertility.

PMID- 29370626
TI  - Re: Associations between Physical Activity and Semen Quality in Young Healthy
      Men.

PMID- 29370627
TI  - Re: Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice.

PMID- 29370628
TI  - Re: Novel Centrifugal Technology for Measuring Sperm Concentration in the Home.

PMID- 29370629
TI  - Re: Comparison of Diagnostic Performance of CT and MRI for Abdominal Staging of
      Pediatric Renal Tumors: A Report from the Children's Oncology Group.

PMID- 29370630
TI  - "Targeted Top Down" Approach for the Investigation of UTI: A 10-Year Follow-up
      Study in a Cohort of 1000 Children.

PMID- 29370631
TI  - Re: Low Prevalence of Latex Allergy in Children with Spinal Dysraphism in Non
      Latex-Free Environment.

PMID- 29370632
TI  - Re: Early Steroid Withdrawal Results in Improved Patient and Graft Survival and
      Lower Risk of Post-Transplant Cardiovascular Risk Profiles: A Single-Center 10
      Year Experience.

PMID- 29370633
TI  - Re: A Qualitative Exploration of the Experiences of Children with Spina Bifida
      and Their Parents around Incontinence and Social Participation.

PMID- 29370634
TI  - Re: Are Octogenarians with End-Stage Renal Disease Candidates for Renal
      Transplantation?

PMID- 29370635
TI  - Re: Risk of Renal Cell Carcinoma among Kidney Transplant Recipients in the United
      States.

PMID- 29370637
TI  - Re: National Health Spending: Faster Growth in 2015 as Coverage Expands and
      Utilization Increases.

PMID- 29370636
TI  - Re: At Federally Funded Health Centers, Medicaid Expansion was Associated with
      Improved Quality of Care.

PMID- 29370638
TI  - Re: The Selection of Procedures in One-Stage Urethroplasty for Treatment of
      Coexisting Urethral Strictures in Anterior and Posterior Urethra.

PMID- 29370639
TI  - Re: Low-Volume vs High-Volume Centers and Management of Fournier's Gangrene in
      Washington State.

PMID- 29370640
TI  - Re: Outcomes for Management of Lichen Sclerosus Urethral Strictures by 3
      Different Techniques.

PMID- 29370641
TI  - Re: Stone Former Urine Proteome Demonstrates a Cationic Shift in Protein
      Distribution Compared to Normal.

PMID- 29370642
TI  - Re: Total Phallic Reconstruction Using the Radial Artery Based Forearm Free Flap
      after Traumatic Penile Amputation.

PMID- 29370643
TI  - Re: Oxalate Content of Taro Leaves Grown in Central Vietnam.

PMID- 29370644
TI  - Re: Multiple Sclerosis and Nephrolithiasis: A Matched-Case Comparative Study.

PMID- 29370645
TI  - Re: Use of Polymer Conjugates for the Intraperoxisomal Delivery of Engineered
      Humanalanine:Glyoxylate Aminotransferase as a Protein Therapy for Primary
      Hyperoxaluria Type I.

PMID- 29370646
TI  - Re: Mortality, Morbidity and Healthcare Expenditures after Local Tumour Ablation
      or Partial Nephrectomy for T1A Kidney Cancer.

PMID- 29370647
TI  - Re: Findings and Impact of Early Imaging after Partial Nephrectomy.

PMID- 29370648
TI  - Re: Genital Human Papillomavirus Infection Progression to External Genital
      Lesions: The HIM Study.

PMID- 29370649
TI  - Re: Papillary Recurrence of Bladder Cancer at First Evaluation after Induction
      Bacillus Calmette-Guerin Therapy: Implication for Clinical Trial Design.

PMID- 29370650
TI  - Re: Padeliporfin Vascular-Targeted Photodynamic Therapy versus Active
      Surveillance in Men with Low-Risk Prostate Cancer (CLIN1001 PCM301): An Open
      Label, Phase 3, Randomised Controlled Trial.

PMID- 29370651
TI  - Re: Change in Salvage Radiotherapy Management Based on Guidance with FACBC
      (Fluciclovine) PET/CT in Postprostatectomy Recurrent Prostate Cancer.

PMID- 29370652
TI  - Re: Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of
      Patients with Intermediate- or Poor-Risk Germ Cell Tumors.

PMID- 29370653
TI  - Re: The Genomic Landscape of Renal Oncocytoma Identifies a Metabolic Barrier to
      Tumorigenesis.

PMID- 29370654
TI  - Re: Mg(II)-Catechin Nanoparticles Delivering siRNA Targeting EIF5A2 Inhibit
      Bladder Cancer Cell Growth In Vitro and In Vivo.

PMID- 29370655
TI  - Re: SOX2 Promotes Lineage Plasticity and Antiandrogen Resistance in TP53- and RB1
      Deficient Prostate Cancer.

PMID- 29370656
TI  - Re: Sacral Neuromodulation: An Effective Treatment for Lower Urinary Tract
      Symptoms in Multiple Sclerosis.

PMID- 29370657
TI  - Re: Symptom Improvement after Prolapse and Incontinence Graft Removal in a Case
      Series of 306 Patients.

PMID- 29370658
TI  - Re: Indoor Cold Exposure and Nocturia: A Cross-Sectional Analysis of the HEIJO
      KYO Study.

PMID- 29370659
TI  - Re: Influence of Voluntary Pelvic Floor Muscle Contraction and Pelvic Floor
      Muscle Training on Urethral Closure Pressures: A Systematic Literature Review.

PMID- 29370660
TI  - [The Predictive Factors of Stent Failure in the Treatment of Malignant Extrinsc
      Ureteral Obstruction Using Internal Ureteral Stents].
AB  - In this study, we retrospectively reviewed the experiences at our single
      institute in the treatment of malignant extrinsic ureteral obstruction (MUO)
      using ureteral stents to investigate the clinical outcomes and the predictive
      factors of stent failure. In 52 ureters of 38 patients who had radiologically
      significant hydronephrosis due to MUO, internal ureteral stents (The BARD(R)
      INLAY(TM) ureteral stent set) were inserted. The median follow-up interval after
      the initial stent insertion was 124.5 days (4-1,120). Stent failure occurred in 8
      ureters (15.4%) of the 7 patients. The median interval from the first stent
      insertion to stent failure was 88 days (1-468). A Cox regression multivariate
      analysis showed that the significant predictors of stent failure were bladder
      invasion. Based on the possibility of stent failure, the adaptation of the
      internal ureteral stent placement should be considered especially in a patient
      with MUO combined with bladder invasion.

PMID- 29370661
TI  - [The Study of Surgical Outcome for Robotic-Assisted Laparoscopic Radical
      Prostatectomy : Experience of a Single Surgeon with 70 Initial Cases].
AB  - We investigated the surgical outcome for robotic-assisted laparoscopic radical
      prostatectomy (RALP) withinitial 70 prostate cancer cases performed by a single
      surgeon between June 2014 and May 2016. The surgeon had a previous experience of
      more than 400 cases of laparoscopic radical prostatectomy (LRP). Comparative
      study of the surgical outcome was made between the first 35 patients (group 1)
      and the second 35 patients (group 2). The console time without lymph node
      dissection significantly decreased from group 1 to 2 (193 min vs 158 min,
      p=0.002). Among specific 3 parts of the console operation (part 1 : until the
      bladder neck transection, part 2 : until the prostate removal and part 3 :
      urethrovesical anastomosis), duration of parts 1 and 2 similarly decreased witha
      significant difference of 0. 001 and 0. 002, respectively. Continence recovery
      rates 1 month after RALP were significantly higher in group 2 than in group 1
      (group1 : 48.5% vs group 2 : 74.2%, p=0.02). Between groups 1 and 2, the positive
      surgical margin rates of both pT2 and pT3 were similar (group 1 : 20. 8 and 50.
      0%, group 2 : 17. 2 and 50. 0%, respectively). The perioperative 8 complications
      (11.4%) were classified into Clavien-Dindo grades 1 and 2. Our surgical outcome
      of initial 70 RALP cases was considered as comparable to that reported from the
      high volume centers.

PMID- 29370662
TI  - [Availability of Local Therapy to Castration-Resistant Prostate Cancer for M0
      Patients with Initial Prostate Specific Antigen 100 ng/ml or Higher].
AB  - Prostate cancer patients with initial PSA 100 ng/ml or greater who received
      transrectal ultrasoundguided prostate biopsy and were staged as M0 by imaging
      studies from 2011 to 2014 in seven hospitals, were enrolled in the study.
      Castration-resistant prostate cancer (CRPC)-free survival was compared between
      the two treatment groups : androgen deprivation therapy (ADT) alone and ADT plus
      local therapy. Of 142 prostate cancer patients with initial PSA 100 ng/ml or
      greater, 49 (34.5%) had no metastases and final analysis was performed on 46
      patients. Thirty one M0 patients received ADT alone, and 15 received ADT plus
      local therapy. During follow-up (median 31 months, range 1-56 months) 13 patients
      (42%) in the ADT alone group progressed to CRPC. One- and two-year CRPC-free
      survival rates were 72.5 and 53%, respectively. No patients with ADT plus local
      therapy developed CRPC, and time to CRPC was prolonged significantly (p=0.002).
      On multivariate analysis for the group with ADT alone, PSA nadir of more than 0.
      2 ng/ml and cN1 were independent predictors for progression to CRPC (p=0.009,
      0.031). About one third of prostate cancer patients with initial PSA 100 ng/ml or
      greater had clinically no metastases. Local therapy to prostate combined with ADT
      may prolong time to CRPC compared with ADT alone. A subset of men with a PSA
      nadir of more than 0.2 ng/ml after ADT and cN1 could benefit from local therapy.

PMID- 29370663
TI  - [A Case of Retroperitoneal Cavernous Hemangioma Difficult to Differentiate from
      Retroperitoneal Liposarcoma].
AB  - We report a case of retroperitoneal cavernous hemangioma. A 77-year-old woman
      complaining of nausea was admitted to a different hospital in September 2013.
      Computed tomography (CT) detected a retroperitoneal mass in the left pararenal
      space. Three years later, repeated CT showed that the tumor had gradually grown
      in size. On dynamic contrast-enhanced magnetic resonance imaging (MRI), the tumor
      demonstrated radiographic signs of a liposarcoma. Resection of the mass with left
      nephrectomy was performed in June 2016, and histopathology showed cavernous
      hemangioma. Clinical diagnosis of cavernous hemangioma is difficult, and imaging
      modalities, including CT and MRI, may not be conclusive. The final diagnosis in
      most cases is established through surgery. This is the 29th case of
      retroperitoneal cavernous hemangioma to be reported in Japan.

PMID- 29370664
TI  - [A Case of Retroperitoneal Teratoma Difficult to Distinguish from Adrenal Tumor].
AB  - Retroperitoneal tumor is a rare tumor, with an incidence of 0.2 to 0.8%. Among
      such tumors, the frequency of teratomas ranges from 6 to 18%, and adult cases are
      extremely rare. We report a mature teratoma that occurred in the retroperitoneum
      of 43-year-old woman. She experienced back pain and a left adrenal gland mass was
      detected on computed tomography. Computed tomography and magnetic resonance
      imaging findings showed a cyst made of fat and calcification, but it was
      difficult to distinguish retroperitoneal teratoma from adrenal tumor in this
      case. The tumor was removed, and was mainly composed of a hair ball and fat.
      Pathological examination showed that the tumor was composed of stratified
      squamous epithelium, keratinizing component, cartilage, and bronchial epithelium,
      while no continuity with the adrenal gland was observed. Therefore, the tumor was
      diagnosed as a retroperitoneal teratoma.

PMID- 29370665
TI  - [A Case of Right Pyonephrosis Caused by Renal Pelvic Cancer].
AB  - A 47-year-old woman who was diagnosed with right pyelonephritis by a local
      physician, but failed to respond to antimicrobial chemotherapy, was referred to
      our hospital. Here, the diagnosis of right pyonephrosis was confirmed byabdominal
      computed tomography(CT). Retrograde pyelography(RP) revealed a severe stricture
      at the ureteropelvic junction, and it was considered difficult to advance a
      guidewire through the stricture. Urine cytologywas pseudo-positive ; thus, the
      possibilityof a malignant tumor of the urinarytract could not be ruled out.
      Therefore, right nephroureterectomywas performed. The final, histopathological
      diagnosis was urothelial carcinoma, (G2, pT3). After surgery, the signs and
      symptoms of the infection were rapidlyameliorated ; however, swelling of the
      lymph-nodes between the aorta and vena cava was observed, which was considered to
      be metastasis. Therefore, 4 courses of gemcitabine +cisplatin therapywere
      administered, which resulted in complete resolution of the lymph-node swelling.
      The patient has remained free of recurrence for 2 years after surgery.

PMID- 29370666
TI  - [Urethral Hemangioma with Repeated Urinary Retention by Posterection Hematuria].
AB  - A 73-year-old man presented to our hospital due to postejaculation gross
      hematuria and dysuria. Three months after onset, urinary retention occurred
      repeatedly. Under general anesthesia, cystourethroscopy following drug-induced
      erection was performed. A solitary sessile lesion with varicosis was found
      between the verumontanum and external sphincter. The tumor was resected
      endoscopically and recurrence was not observed during the follow-up period.
      Histological examination revealed a cavernous hemangioma of the urethra.
      Urologists should keep in mind that urethral hemangioma can be a cause of
      hematuria after erection or ejaculation.

PMID- 29370668
TI  - The potential role of exercise in chronic stress-related changes in AMPA receptor
      phenotype underlying synaptic plasticity.
AB  - PURPOSE: Chronic stress can cause disturbances in synaptic plasticity, such as
      longterm potentiation, along with behavioral defects including memory deficits.
      One major mechanism sustaining synaptic plasticity involves the dynamics and
      contents of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
      (AMPARs) in the central nervous system. In particular, chronic stress-induced
      disruption of AMPARs includes it abnormal expression, trafficking, and calcium
      conductance at glutamatergic synapses, which contributes to synaptic plasticity
      at excitatory synapses. Exercise has the effect of promoting synaptic plasticity
      in neurons. However, the contribution of exercise to AMPAR behavior under chronic
      stressful maladaptation remains unclear. METHODS: The present article reviews the
      information about the chronic stress-related synaptic plasticity and the role of
      exercise from the previous-published articles. RESULTS: AMPAR-mediated synaptic
      transmission is an important for chronic stress-related changes of synaptic
      plasticity, and exercise may at least partly contribute to these episodes.
      CONCLUSION: The present article discusses the relationship between AMPARs and
      synaptic plasticity in chronic stress, as well as the potential role of exercise.

PMID- 29370667
TI  - Nutritional needs in the professional practice of swimming: a review.
AB  - PURPOSE: Swimming requires developing a high aerobic and anaerobic capacity for
      strength and technical efficiency. The purpose of this study was to establish the
      nutritional requirements and dietary strategies that can optimize swimming
      performance. METHODS: Several related studies retrieved from the databases,
      Dialnet, Elsevier, Medline, Pubmed, and Web of Science, through keyword search
      strategies were reviewed. RESULTS: The recommended carbohydrate intake ranges
      between 6-10-12 g/kg/d, protein 2 g/kg/d, and fat should surpass 20-25% of the
      daily intake. CONCLUSION: Performance can be optimized with a hydration plan, as
      well as adequate periodization of supplements, such as caffeine, creatine, sodium
      bicarbonate, B-alanine, beetroot juice, Vitamin D, bovine colostrum, and HMB.

PMID- 29370669
TI  - The role of habitual physical activity on arterial stiffness in elderly
      Individuals: a systematic review and meta-analysis.
AB  - PURPOSE: Physical inactivity behavior at middle age or older is a major risk
      factor for cardiovascular disease. However, the effects of levels of habitual
      physical activity on arterial stiffness in elderly population remain unclear
      currently. Therefore, the purpose of this study was to demonstrate whether the
      effects of habitual physical activity could attenuate arterial stiffness in
      elderly individuals via a meta-analysis. METHODS: We searched the Medline and
      Embase databases from January 1997 through November 2017, using the medical
      subject headings "older population", "physical activity" (e.g., walking, cycling,
      climbing, and any participation in sports), "arterial stiffness", "pulse wave
      velocity", and "cardiovascular health" published in English. Six articles (2,932
      participants) were included in this meta-analysis. We investigated the effects of
      habitual physical activity on arterial stiffness, which was measured by the pulse
      wave velocity. RESULTS: Results confirmed heterogeneity (Q-value = 160.691, p =
      0.000, I2 = 96.888) between individual studies. The effect size was calculated
      using random effect model. It has shown that physically active individuals have
      significantly lower arterial stiffness than their sedentary peers do
      (standardized mean difference: -1.017 +/- 0.340, 95% confidence interval: -1.684
      ~ -0.350, p = 0.003). CONCLUSION: Findings of our systematic review and meta
      analysis indicate that habitual physical activity can significantly ameliorate
      arterial stiffness in the elderly population.

PMID- 29370670
TI  - Comparison of body composition between fashion models and women in general.
AB  - PURPOSE: The present study compared the physical characteristics and body
      composition of professional fashion models and women in general, utilizing the
      skinfold test. METHODS: The research sample consisted of 90 professional fashion
      models presently active in Korea and 100 females in the general population, all
      selected through convenience sampling. Measurement was done following
      standardized methods and procedures set by the International Society for the
      Advancement of Kinanthropometry. Body density (mg/ mm) and body fat (%) were
      measured at the biceps, triceps, subscapular, and suprailiac areas. RESULTS: The
      results showed that the biceps, triceps, subscapular, and suprailiac areas of
      professional fashion models were significantly thinner than those of women in
      general (p<.001), and that their waist size was also significantly smaller
      (p<.001). However, hip circumference showed no significant difference. Body mass
      index, waist-to-hip ratio, and body fat (%) in professional fashion models were
      significantly lower than those in women in general (p<.001), while the body
      density in professional fashion models was significantly greater (p<.001).
      CONCLUSION: Body density in professional fashion models is higher, due to taller
      stature, than in women in general. Moreover, there is an effort on the part of
      fashion models to lose weight in order to maintain a thin body and a low weight
      for occupational reasons.

PMID- 29370671
TI  - The synergistic effect of protein complex supplementation combined with 12 weeks
      of resistance training on isokinetic muscular function in untrained young males.
AB  - PURPOSE: Resistance exercise training (RET) and an additional intake of dietary
      protein supplements may improve muscle mass and muscular function, and reduce
      inflammatory markers. The types, amount, and timing of dietary protein
      supplements are important for the synergistic effects of resistance training and
      dietary protein supplements. We hypothesized that a 25.1 g protein complex
      supplement taken for 12 weeks, immediately before and after resistance exercise,
      would enhance fat free mass and isokinetic muscular function in young untrained
      males. METHODS: Eighteen participants were randomly assigned to a placebo (n=8)
      or protein complex supplement groups (n=10). The RET was a supervised progressive
      program, 3 times per week for 12-weeks, and was performed progressing 80% of
      their one repetition maximum (1-RM). Body composition, blood pressure, plasma
      inflammatory markers, lipid level and isokinetic muscular function were assessed
      before and after the study period. RESULTS: There was a significant interaction
      effect in C-reactive protein (CRP) (p =0.044) among blood vessel inflammatory
      markers. The protein complex supplement group had shown more effective
      improvement at 12 weeks intervention compared to the placebo group in isokinetic
      muscular function. There was a significant interaction effect in peak torque at
      60 degrees/sec leg extension (p =0.044), total work at 240 degrees/sec leg
      extension (p =0.025), and total work at 240 degrees/sec leg flexion (p =0.011).
      CONCLUSION: Protein complex supplementation during RET appears more effective
      than RET alone in improving isokinetic muscular function for 12 weeks in
      untrained young men.

PMID- 29370672
TI  - Weight reduction does not induce an undesirable decrease in muscle mass, muscle
      strength, or physical performance in men with obesity: a pilot study.
AB  - PURPOSE: To date, there have been no reports on whether weight reduction causes
      decreases in muscle mass, muscle strength, or physical performance that could
      lead to health problems. Thus, in this pilot study, we investigated the
      appropriateness of the changes in muscle mass, muscle strength and physical
      performance after weight reduction. METHODS: Obese men who completed a weight
      reduction program to decrease and maintain a body mass index (BMI) of less than
      25 kg/m2 for one year were recruited for the study. One year after the completion
      of a weight reduction program, the participants' muscle mass, muscle strength,
      and physical performance were compared with those in a reference group composed
      of individuals whose BMI was less than 25 kg/m2. Whole-body scanning was
      performed using dual-energy X-ray absorptiometry to analyze muscle mass. Handgrip
      strength and knee extensor strength were measured to evaluate arm and leg muscle
      strength, respectively. For physical performance, a jump test was employed.
      RESULTS: The results showed that the biceps, triceps, subscapular, and suprailiac
      areas of professional fashion models were significantly thinner than those of
      women in general (p<.001), and that their waist size was also significantly
      smaller (p<.001). However, hip circumference showed no significant difference.
      Body mass index, waist-to-hip ratio, and body fat (%) in professional fashion
      models were significantly lower than those in women in general (p<.001), while
      the body density in professional fashion models was significantly greater
      (p<0.001). CONCLUSION: Weight reduction participants showed an average reduction
      in body weight of -16.47%. Normalized arm muscle mass and handgrip strength were
      significantly greater in the weight reduction group than in the reference group;
      however, no significant differences were detected between the two groups with
      respect to the other variables. After one year, there were no significant
      differences between the two groups.

PMID- 29370673
TI  - Arc/Arg3.1 protein expression in dorsal hippocampal CA1, a candidate event as a
      biomarker for the effects of exercise on chronic stress-evoked behavioral
      abnormalities.
AB  - PURPOSE: Chronic stress is a risk factor for behavioral deficits, including
      impaired memory processing and depression. Exercise is well known to have
      beneficial impacts on brain health. METHODS: Mice were forced to treadmill
      running (4-week) during chronic restraint stress (6h/21d), and then behavioral
      tests were conducted by Novel object recognition, forced swimming test: FST,
      sociality test: SI. Dissected brain was stained with anti-calbindin-d28k and anti
      Arc antibodies. Also, mice were treated with CX546 intraperitoneally during
      chronic restraint stress, and behavioral tests were assessed using Morris water
      maze, FST, and SI. Dissected brain was stained with anti-Arc antibody. RESULTS:
      The current study demonstrated that chronic stress-induced impairment of memory
      consolidation and depression-like behaviors, along with the changes in calbindin
      d28k and Arc protein levels in the hippocampal CA1 area, were attenuated by
      regular treadmill running. Further, prolonged ampakine treatment prevented
      chronic stress-evoked behavioral abnormalities and nuclear Arc levels in
      hippocampal CA1 neurons. Nuclear localization of Arc protein in hippocampal CA1
      neurons, but not total levels, was correlated with behavioral outcome in
      chronically stressed mice in response to a regular exercise regimen. CONCLUSION:
      These results suggest that nuclear levels of Arc are strongly associated with
      behavioral changes, and highlight the role of exercise acting through an alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)
      mediated mechanisms in a chronic stress-induced maladaptive condition.

PMID- 29370674
TI  - Effects of acute voluntary loaded wheel running on BDNF expression in the rat
      hippocampus.
AB  - PURPOSE: Voluntary loaded wheel running involves the use of a load during a
      voluntary running activity. A muscle-strength or power-type activity performed at
      a relatively high intensity and a short duration may cause fewer apparent
      metabolic adaptations but may still elicit muscle fiber hypertrophy. This study
      aimed to determine the effects of acute voluntary wheel running with an
      additional load on brain-derived neurotrophic factor (BDNF) expression in the rat
      hippocampus. METHODS: Ten-week old male Wistar rats were assigned randomly to a
      (1) sedentary (Control) group; (2) voluntary exercise with no load (No-load)
      group; or (3) voluntary exercise with an additional load (Load) group for 1-week
      (acute period). The expression of BDNF genes was quantified by real-time PCR.
      RESULTS: The average distance levels were not significantly different in the No
      load and Load groups. However, the average work levels significantly increased in
      the Load group. The relative soleus weights were greater in the No-load group.
      Furthermore, loaded wheel running up-regulated the BDNF mRNA level compared with
      that in the Control group. The BDNF mRNA levels showed a positive correlation
      with workload levels (r=0.75), suggesting that the availability of multiple
      workload levels contributes to the BDNF-related benefits of loaded wheel running
      noted in this study. CONCLUSION: This novel approach yielded the first set of
      findings showing that acute voluntary loaded wheel running, which causes muscular
      adaptation, enhanced BDNF expression, suggesting a possible role of high
      intensity short-term exercise in hippocampal BDNF activity.

PMID- 29370676
TI  - A clinical update on metformin and lung cancer in diabetic patients.
AB  - Diabetes mellitus (DM) is frequently increased in many countries and become a
      serious health problem worldwide. Diabetes is associated with dysfunction of
      different organs such as heart, eyes, blood vessels, nerves, and kidneys. There
      is a strong connection between diabetes and cancer. Metformin is one of the most
      commonly prescribed oral antidiabetic medicines and it is suggested as the first
      line therapy due to its comparatively safe, inexpensive, effective and well
      tolerated. Some of the in vitro and in vivo investigations proved that metformin
      may have a direct anticancer action by preventing the proliferation of malignant
      cells and formations of the colony, inducing arrest of cell cycle and apoptosis
      and suppressing tumor growth. The antiproliferative mechanism of metformin alone
      or in combination with various chemotherapeutic agents is complex and involves
      several beneficial roles. In this regard, clinical studies are required to
      explain these roles. In the coming future, the use of metformin, alone or in
      combination with current chemotherapy, might be a conventional approach to
      effectually manage lung cancer. This mini-review provides a critical overview of
      currently available clinical trials investigating the effects of metformin in
      lung cancer.

PMID- 29370675
TI  - High blood pressure, Alzheimer disease and antihypertensive treatment.
AB  - Alzheimer's disease (AD), the most common form of dementia, is a complex disease,
      the mechanisms of which are poorly understood. AD represents 70% of all dementia
      cases, affecting up to 50% of elderly persons aged 85 or older, with functional
      dependence, poor quality of life, institutionalization and mortality. Advanced
      age is the main risk factor of AD, that is why population ageing, due to life
      expectancy improvements, increases AD incidence and prevalence, as well as the
      economic, social, and emotional costs associated with this illness. Existing anti
      AD drugs present some limitations, as they target specific downstream
      neurochemical abnormalities while the upstream underlying pathology continues
      unchecked. Chronic hypertension has been suggested as one of the largest
      modifiable risk factors for developing AD. At least 25% of all adults and more
      than 50% of those over 60 years of age have hypertension. Epidemiological studies
      have shown that hypertension is a risk factor for dementia and AD, but the
      association is complex. Some studies have demonstrated that antihypertensive
      drugs can reduce the risk of AD. This review focuses on current knowledge about
      the relationship between chronic hypertension and AD as well as antihypertensive
      treatment effect on AD pathogenesis and its clinical outcomes.

PMID- 29370677
TI  - Current updates on biological and pharmacological activities of doxycycline.

PMID- 29370678
TI  - Advancements in nano drug delivery systems: a challenge for biofilms in
      respiratory diseases.

PMID- 29370679
TI  - Fecal calprotectin: beyond intestinal organic diseases.
AB  - Fecal calprotectin (FC) is a calcium-binding protein with antimicrobic,
      imunomodulatory and antiproliferative properties that is mainly found in the
      cytoplasm of neutrophil granulocytes. During the last decades, FC became an
      increasingly useful tool both for gastroenterologists and for general
      practitioners for distinguishing inflammatory bowel disease (IBD) from irritable
      bowel syndrome. FC correlates with clinical scoring systems and endoscopic
      lesions in IBD and is considered a reliable biomarker for the prediction of
      clinical relapse or remission. However, FC elevation could be observed also in
      other gastrointestinal pathological conditions including infective colitis,
      microscopic colitis, eosinophilic colitis, adenomas and colorectal cancer. In
      addition, there are several non-pathological conditions that can lead to altered
      FC values. In this review, we aimed to point out individual, environmental and
      method-related factors that can affect FC measurement and thus its clinical
      interpretation.

PMID- 29370682
TI  - Rapid qualitative review of ethical issues surrounding healthcare for pregnant
      women or women of reproductive age in epidemic outbreaks.
AB  - This article describes, categorizes, and discusses the results of a rapid
      literature review aiming to provide an overview of the ethical issues and
      corresponding solutions surrounding pregnancies in epidemic outbreaks. The review
      was commissioned by the World Health Organization to inform responses to the Zika
      outbreak that began in 2015. Due to the urgency of the response efforts that
      needed to be informed by the literature search, a rapid qualitative review of the
      literature published in PubMed was conducted. The search and analysis were based
      on the operationalization of 3 key concepts: ethics, pregnancy, and epidemic
      outbreak. Ethical issues and solutions were interpreted within a principlist
      framework. The data were analyzed using qualitative content analysis. The search
      identified 259 publications, of which the full text of 23 papers was read. Of
      those, 20 papers contained a substantive part devoted to the topic of interest
      and were therefore analyzed further. We clustered the ethical issues and
      solutions around 4 themes: uncertainty, harms, autonomy/liberty, and
      effectiveness. Recognition of the identified ethical issues and corresponding
      solutions can inform and improve response efforts, public health planning,
      policies, and decision-making, as well as the activities of medical staff and
      counselors who practice before, during, or after an epidemic outbreak that
      affects pregnant women or those of reproductive age. The rapid review format
      proved to be useful despite its limited data basis and expedited review process.

PMID- 29370680
TI  - Health effects of environmental pollution in population living near industrial
      complex areas in Korea.
AB  - Several epidemiological studies have reported an association between
      environmental pollution and various health conditions in individuals residing in
      industrial complexes. To evaluate the effects of pollution from industrial
      complex on human health, we performed a pooled analysis of environmental
      epidemiologic monitoring data for residents living near national industrial
      complexes in Korea. The respiratory and allergic symptoms and the prevalence of
      acute and chronic diseases, including cancer, were used as the outcome variables
      for health effects. Multiple logistic regression analysis was used to analyze the
      relationship between exposure to pollution from industrial complexes and health
      conditions. After adjusting for age, sex, smoking status, occupational exposure,
      level of education, and body mass index, the residents near the industrial
      complexes were found to have more respiratory symptoms, such as cough (odds ratio
      [OR], 1.18; 95% confidence interval [CI], 1.06 to 1.31) and sputum production
      (OR, 1.13; 95% CI, 1.03 to 1.24), and symptoms of atopic dermatitis (OR, 1.10;
      95% CI, 1.01 to 1.20). Among residents of the industrial complexes, the
      prevalence of acute eye disorders was approximately 40% higher (OR, 1.39; 95% CI,
      1.04 to 1.84) and the prevalence of lung and uterine cancer was 3.45 times and
      1.88 times higher, respectively, than those among residents of the control area.
      This study showed that residents living in the vicinity of industrial complexes
      have a high risk of acute and chronic diseases including respiratory and allergic
      conditions. These results can be used as basic objective data for developing
      health management measures for individuals residing near industrial complexes.

PMID- 29370683
TI  - Systematic review of the published data on the worldwide prevalence of John
      Cunningham virus in patients with multiple sclerosis and neuromyelitis optica.
AB  - OBJECTIVES: John Cunningham virus (JCV) is a polyoma virus that infects humans,
      mainly in childhood or adolescence, and presents no symptomatic manifestations.
      JCV can cause progressive multifocal leukoencephalopathy (PML) in
      immunosuppressed individuals, including those undergoing treatment for multiple
      sclerosis (MS) and neuromyelitis optica (NMO). PML is a severe and potentially
      fatal disease of the brain. The prevalence of JCV antibodies in human serum has
      been reported to be between 50.0 and 90.0%. The aim of the present study was to
      review worldwide data on populations of patients with MS and NMO in order to
      establish the rates of JCV seropositivity in these individuals. METHODS: The
      present review followed the PRISMA (Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses) guidelines and used the following search terms: "JCV"
      OR "JC virus" AND "multiple sclerosis" OR "MS" OR "NMO" OR "neuromyelitis optica"
      AND "prevalence." These terms were searched for both in smaller and in larger
      clusters of words. The databases searched included PubMed, MEDLINE, SciELO,
      LILACS, Google Scholar, and Embase. RESULTS: After the initial selection, 18
      papers were included in the review. These articles reported the prevalence of JCV
      antibodies in the serum of patients with MS or NMO living in 26 countries. The
      systematic review identified data on 29,319 patients with MS/NMO and found that
      57.1% of them (16,730 individuals) were seropositive for the anti-JCV antibody
      (range, 40.0 to 69.0%). CONCLUSIONS: The median worldwide prevalence of JCV among
      adults with MS or NMO was found to be 57.1%.

PMID- 29370684
TI  - Epidemiological characteristics of scrub typhus on the Jeju Island.

PMID- 29370685
TI  - The current status of health data on Korean children and adolescents.
AB  - Childhood and adolescence are critical periods that affect adults' health status.
      Therefore, the factors influencing the health of children and adolescents should
      be analyzed. In Korea, a wide range of youth-related health data has been
      obtained, both on the regional level and on the national level. This report
      summarizes the current status of studies related to the health of Korean children
      and adolescents. Data for which open access is offered include the Korea Youth
      Risk Behavior Web-based Study, the Panel Study on Korean Children, the Korean
      Youth Panel Survey, the Korean Children and Youth Panel Survey, and the Student
      Health Examination. In addition, the Health Examination of Korean Youth Outside
      of School, the Korean Children and Adolescents Obesity Cohort Study, the Korean
      Children's Environmental Health Study, the Korea Youth Media Use and Harmful
      Environment Survey, the Comprehensive Survey of Korean Youth, and the
      Multicultural Adolescents Panel Study are summarized.

PMID- 29370686
TI  - Experience of 16 years and its associated challenges in the Field Epidemiology
      Training Program in Korea.
AB  - OBJECTIVES: The field epidemiologist system of South Korea, which employs public
      health doctors who are relatively more readily available, was created in 1999 to
      ensure a ready supply of experts for epidemiological investigations and enable an
      effective response for new and reemerging infectious diseases. However, the 2015
      outbreak of Middle East Respiratory Syndrome revealed limitations in the existing
      systems of management of field epidemiologists and communicable diseases.
      METHODS: The present study aims to evaluate data on current states,
      administrative reports, and other literature on the field epidemiologist system
      that has been in place in South Korea for 16 years since 1999 and to suggest
      appropriate future improvements in this system. RESULTS: By suggesting methods to
      evaluate the field epidemiologist system and training programs and by suggesting
      ways for the Korea Centers for Disease Control and Prevention to conduct
      evaluations on its own, the present study provides supporting evidence for
      improvement of systems for training of experts in epidemiological investigations.
      Moreover, based on the findings, this study also suggests methods to
      systematically train experts in communicable diseases management and a
      sustainable system to establish the basis of and develop strategies for a
      systematic and phased management of field epidemiologist training programs.
      CONCLUSIONS: The present study suggests the possibility of establishing dedicated
      training facilities, revising the guidelines on training and improvement of the
      competency of public health experts, while not limiting the scope of application
      to communicable diseases.

PMID- 29370687
TI  - Mechanisms and Physiological Roles of Mitophagy in Yeast.
AB  - Mitochondria are responsible for supplying of most of the cell's energy via
      oxidative phosphorylation. However, mitochondria also can be deleterious for a
      cell because they are the primary source of reactive oxygen species, which are
      generated as a byproduct of respiration. Accumulation of mitochondrial and
      cellular oxidative damage leads to diverse pathologies. Thus, it is important to
      maintain a population of healthy and functional mitochondria for normal cellular
      metabolism. Eukaryotes have developed defense mechanisms to cope with aberrant
      mitochondria. Mitochondria autophagy (known as mitophagy) is thought to be one
      such process that selectively sequesters dysfunctional or excess mitochondria
      within double-membrane autophagosomes and carries them into lysosomes/vacuoles
      for degradation. The power of genetics and conservation of fundamental cellular
      processes among eukaryotes make yeast an excellent model for understanding the
      general mechanisms, regulation, and function of mitophagy. In budding yeast, a
      mitochondrial surface protein, Atg32, serves as a mitochondrial receptor for
      selective autophagy that interacts with Atg11, an adaptor protein for selective
      types of autophagy, and Atg8, a ubiquitin-like protein localized to the isolation
      membrane. Atg32 is regulated transcriptionally and post-translationally to
      control mitophagy. Moreover, because Atg32 is a mitophagy-specific protein,
      analysis of its deficient mutant enables investigation of the physiological roles
      of mitophagy. Here, we review recent progress in the understanding of the
      molecular mechanisms and functional importance of mitophagy in yeast at multiple
      levels.

PMID- 29370688
TI  - Development of Research into Autophagic Lysosome Reformation.
AB  - Autophagy is a lysosome-dependent degradation process that is essential for
      maintaining cellular homeostasis. In recent years, more studies have focused on
      the late stages of autophagy. Our group discovered and studied the terminal step
      of autophagy, namely autophagic lysosome reformation (ALR). ALR is the process
      that regenerates functional lysosomes from autolysosomes, thus maintaining
      lysosome homeostasis. ALR involves clathrin-mediated membrane budding from
      autolysosomes, elongation of membrane tubules along microtubules with the pulling
      force provided by the motor protein KIF5B, proto-lysosome scission by dynamin 2,
      and finally maturation of proto-lysosomes to functional lysosomes. In this
      review, we will summarize progress in unveiling the molecular mechanisms
      underlying ALR and its potential pathophysiological roles.

PMID- 29370689
TI  - A Molecular Approach to Mitophagy and Mitochondrial Dynamics.
AB  - Mitochondrial quality control systems are essential for the maintenance of
      functional mitochondria. At the organelle level, they include mitochondrial
      biogenesis, fusion and fission, to compensate for mitochondrial function, and
      mitophagy, for degrading damaged mitochondria. Specifically, in mitophagy, the
      target mitochondria are recognized by the autophagosomes and delivered to the
      lysosome for degradation. In this review, we describe the mechanisms of mitophagy
      and the factors that play an important role in this process. In particular, we
      focus on the roles of mitophagy adapters and receptors in the recognition of
      damaged mitochondria by autophagosomes. In addition, we also address a functional
      association of mitophagy with mitochondrial dynamics through the interaction of
      mitophagy adaptor and receptor proteins with mitochondrial fusion and fission
      proteins.

PMID- 29370690
TI  - A Structural View of Xenophagy, a Battle between Host and Microbes.
AB  - The cytoplasm in mammalian cells is a battlefield between the host and invading
      microbes. Both the living organisms have evolved unique strategies for their
      survival. The host utilizes a specialized autophagy system, xenophagy, for the
      clearance of invading pathogens, whereas bacteria secrete proteins to defend and
      escape from the host xenophagy. Several molecules have been identified and their
      structural investigation has enabled the comprehension of these mechanisms at the
      molecular level. In this review, we focus on one example of host autophagy and
      the other of bacterial defense: the autophagy receptor, NDP52, in conjunction
      with the sugar receptor, galectin-8, plays a critical role in targeting the
      autophagy machinery against Salmonella; and the cysteine protease, RavZ secreted
      by Legionella pneumophila cleaves the LC3-PE on the phagophore membrane. The
      structure-function relationships of these two examples and the directions of
      future research will be discussed.

PMID- 29370692
TI  - The Role of Autophagy in Systemic Metabolism and Human-Type Diabetes.
AB  - Autophagy is critical for the maintenance of organelle function and intracellular
      nutrient environment. Autophagy is also involved in systemic metabolic
      homeostasis, and its dysregulation can lead to or accelerate the development of
      metabolic disorders. While the role of autophagy in the global metabolism of
      model organisms has been investigated mostly using site-specific genetic knockout
      technology, the impact of dysregulated autophagy on systemic metabolism has been
      unclear. Here, we review recent papers showing the role of autophagy in systemic
      metabolism and in the development of metabolic disorders. Also included are data
      suggesting the role of autophagy in human-type diabetes, which are different in
      several key aspects from murine models of diabetes. The results shown here
      support the view that autophagy modulation could be a new modality for the
      treatment of metabolic syndrome associated with lipid overload and human-type
      diabetes.

PMID- 29370691
TI  - Autophagy Dysregulation and Obesity-Associated Pathologies.
AB  - Autophagy is one of the major degradative mechanisms that can eliminate excessive
      nutrients, toxic protein aggregates, damaged organelles and invading
      microorganisms. In response to obesity and obesity-associated lipotoxic,
      proteotoxic and oxidative stresses, autophagy plays an essential role in
      maintaining physiological homeostasis. However, obesity and its associated stress
      insults can often interfere with the autophagic process through various
      mechanisms, which result in further aggravation of obesity-related metabolic
      pathologies in multiple metabolic organs. Paradoxically, inhibition of autophagy,
      within specific contexts, indirectly produces beneficial effects that can
      alleviate several detrimental consequences of obesity. In this minireview, we
      will provide a brief discussion about our current understanding of the impact of
      obesity on autophagy and the role of autophagy dysregulation in modulating
      obesity-associated pathological outcomes.

PMID- 29370693
TI  - Biological Roles of Alternative Autophagy.
AB  - Atg5 and Atg7 have long been considered as essential molecules for autophagy.
      However, we found that cells lacking these molecules still form autophagic
      vacuoles and perform autophagic protein degradation when subjected to certain
      stressors. During this unconventional autophagy pathway, autophagosomes appeared
      to be generated in a Rab9-dependent manner by the fusion of vesicles derived from
      the trans-Golgi and late endosomes. Therefore, mammalian autophagy can occur via
      at least two different pathways; the Atg5/Atg7-dependent conventional pathway and
      an Atg5/Atg7-independent alternative pathway.

PMID- 29370696
TI  - An Additive-Free, Base-Catalyzed Protodesilylation of Organosilanes.
AB  - We report an additive-free, base-catalyzed C-, N-, O-, and S-Si bond cleavage of
      various organosilanes in mild conditions. The novel catalyst system exhibits high
      efficiency and good functional group compatibility, providing the corresponding
      products in good to excellent yields with low catalyst loadings. Overall, this
      transition-metal-free process may offer a convenient and general alternative to
      current employing excess bases, strong acids, or metal-catalyzed systems for the
      protodesilylation of organosilanes.

PMID- 29370694
TI  - Pexophagy: Molecular Mechanisms and Implications for Health and Diseases.
AB  - Autophagy is an intracellular degradation pathway for large protein aggregates
      and damaged organelles. Recent studies have indicated that autophagy targets
      cargoes through a selective degradation pathway called selective autophagy.
      Peroxisomes are dynamic organelles that are crucial for health and development.
      Pexophagy is selective autophagy that targets peroxisomes and is essential for
      the maintenance of homeostasis of peroxisomes, which is necessary in the
      prevention of various peroxisome-related disorders. However, the mechanisms by
      which pexophagy is regulated and the key players that induce and modulate
      pexophagy are largely unknown. In this review, we focus on our current
      understanding of how pexophagy is induced and regulated, and the selective
      adaptors involved in mediating pexophagy. Furthermore, we discuss current
      findings on the roles of pexophagy in physiological and pathological responses,
      which provide insight into the clinical relevance of pexophagy regulation.
      Understanding how pexophagy interacts with various biological functions will
      provide fundamental insights into the function of pexophagy and facilitate the
      development of novel therapeutics against peroxisomal dysfunction-related
      diseases.

PMID- 29370697
TI  - Cotranslational Incorporation into Proteins of a Fluorophore Suitable for smFRET
      Studies.
AB  - Single-molecule FRET (smFRET) is a powerful tool to investigate conformational
      changes of biological molecules. In general, smFRET studies require protein
      samples that are site-specifically double-labeled with a pair of donor and
      acceptor fluorophores. The common approaches to produce such samples cannot be
      applied when studying the synthesis and folding of the polypeptide chain on the
      ribosome. The best strategy is to incorporate two fluorescent amino acids
      cotranslationally using cell-free protein synthesis systems. Here, we demonstrate
      the cotranslational site-specific incorporation into a model protein of Atto633,
      a dye with excellent photophysical properties, suitable for single molecule
      spectroscopy, together with a second dye using a combination of the sense
      cysteine and the nonsense amber codon. In this work we show that cotranslational
      incorporation of good fluorophores into proteins is a viable strategy to produce
      suitable samples for smFRET studies.

PMID- 29370695
TI  - Autophagy and Longevity.
AB  - Autophagy is an evolutionally conserved cytoplasmic degradation system in which
      varieties of materials are sequestered by a double membrane structure,
      autophagosome, and delivered to the lysosomes for the degradation. Due to the
      wide varieties of targets, autophagic activity is essential for cellular
      homeostasis. Recent genetic evidence indicates that autophagy has a crucial role
      in the regulation of animal lifespan. Basal level of autophagic activity is
      elevated in many longevity paradigms and the activity is required for lifespan
      extension. In most cases, genes involved in autophagy and lysosomal function are
      induced by several transcription factors including HLH-30/TFEB, PHA-4/FOXA and
      MML-1/Mondo in long-lived animals. Pharmacological treatments have been shown to
      extend lifespan through activation of autophagy, indicating autophagy could be a
      potential and promising target to modulate animal lifespan. Here we summarize
      recent progress regarding the role of autophagy in lifespan regulation.

PMID- 29370699
TI  - Vibrational Coherence Controls Molecular Fragmentation: Ultrafast Photodynamics
      of the [Ag2Cl]+ Scaffold.
AB  - The recently introduced pump-probe fragmentation action spectroscopy reveals a
      unique observation of excited state vibrational coherence (430-460 fs) in the
      isolated metal complex [Ag2(Cl)(dcpm)2)]+ (dcpm =
      bis(dicyclohexylphosphino)methane) containing the [Ag2Cl]+ scaffold. After
      photoexcitation by an 1XMCT transition (260 nm) in an ion trap, an unexpected
      correlation between specific fragment ions (loss of HCl/Cl- vs loss of dcpm) and
      the phase of the wave packet is probed (1150 nm). Based on ab initio
      calculations, we assign the primary electronically excited state and ascribe the
      observed coherences (72-78 cm-1) to contain predominantly Ag-Ag stretch
      character. We propose specific probe absorption and vibronic coupling at the
      classical turning points to switch remarkably early on between the different
      fragmentation pathways. The overall excited state dynamics are fitted to a
      multiexponential decay with time constants: 0.2-0.4/3-4/19-26/104-161 ps. These
      findings open new perspectives for further dynamics investigations and possible
      applications in photocatalysis.

PMID- 29370700
TI  - Well-Ordered 4CzIPN ((4s,6s)-2,4,5,6-Tetra(9-H-carbazol-9-yl)isophthalonitrile)
      Layers: Molecular Orientation, Electronic Structure, and Angular Distribution of
      Photoluminescence.
AB  - We fabricated a well-ordered homogeneous monolayer of disk-shaped, carbazolyl
      dicyanobenzene (CDCB)-based thermally activated delayed fluorescence (TADF)
      molecule, i.e., 4CzIPN((4s,6s)-2,4,5,6-tetra(9Hcarbazol-9-yl)isophthalonitrile)
      at room temperature on flat Ag(111), Au(111), and Cu(111) surfaces. The second
      layer of the 4CzIPN was also found to be well ordered. The electronic states of
      the well-ordered monolayer and multilayer of 4CzIPN were found to be nearly
      unchanged from that of the isolated molecule calculated by the density functional
      theory (DFT), suggesting that the ordered layers retain the TADF properties.
      Indeed, we demonstrated the delayed fluorescence and the nearly perfect in-plane
      alignment of the transition dipole moment of a 4CzIPN thin film on glass
      substrate even in an ambient condition. These results indicate that the well
      ordered films of the disc-shaped carbazole-based TADF molecules could potentially
      be utilized in organic light-emitting diode (OLED) devices with high light
      outcoupling efficiency.

PMID- 29370698
TI  - Discovery of a Novel Dibromoquinoline Compound Exhibiting Potent Antifungal and
      Antivirulence Activity That Targets Metal Ion Homeostasis.
AB  - Globally, invasive fungal infections pose a significant challenge to modern human
      medicine due to the limited number of antifungal drugs and the rise in resistance
      to current antifungal agents. A vast majority of invasive fungal infections are
      caused by species of Candida, Cryptococcus, and Aspergillus. Novel antifungal
      molecules consisting of unexploited chemical scaffolds with a unique mechanism
      are a pressing need. The present study identifies a dibromoquinoline compound
      (4b) with broad-spectrum antifungal activity that inhibits the growth of
      pertinent species of Candida (chiefly C. albicans), Cryptococcus, and Aspergillus
      at a concentration of as low as 0.5 MUg/mL. Furthermore, 4b, at a subinhibitory
      concentration, interfered with the expression of two key virulence factors
      (hyphae and biofilm formation) involved in C. albicans pathogenesis. Three yeast
      deletion strains ( cox17Delta, ssa1Delta, and aft2Delta) related to metal ion
      homeostasis were found to be highly sensitive to 4b in growth assays, indicating
      that the compound exerts its antifungal effect through a unique, previously
      unexploited mechanism. Supplementing the media with either copper or iron ions
      reversed the strain sensitivity to 4b, further corroborating that the compound
      targets metal ion homeostasis. 4b's potent antifungal activity was validated in
      vivo, as the compound enhanced the survival of Caenorhabditis elegans infected
      with fluconazole-resistant C. albicans. The present study indicates that 4b
      warrants further investigation as a novel antifungal agent.

PMID- 29370701
TI  - Quasiharmonic Analysis of the Energy Landscapes of Dihydrofolate Reductase from
      Piezophiles and Mesophiles.
AB  - A quasiharmonic analysis (QHA) method is used to compare the potential energy
      landscapes of dihydrofolate reductase (DHFR) from a piezophile (pressure-loving
      organism), Moritella profunda (Mp), and a mesophile, Escherichia coli (Ec). The
      QHA method considers atomic fluctuations of the protein as motions of an atom in
      a local effective potential created by neighboring atoms and quantitates it in
      terms of effective force constants, isothermal compressibilities, and thermal
      expansivities. The analysis indicates that the underlying potential energy
      surface of MpDHFR is inherently softer than that of EcDHFR. In addition, on
      picosecond time scales, the energy surfaces become more similar under the growth
      conditions of Mp and Ec. On these time scales, DHFR behaves as expected; namely,
      increasing temperature makes the effective energy minimum less steep because
      thermal fluctuations increase the available volume, whereas increasing pressure
      steepens it because compression reduces the available volume. Our longer
      simulations show that, on nanosecond time scales, increasing temperature has a
      similar effect as on picosecond time scales because thermal fluctuations increase
      the volume even more on a longer time scale. However, these simulations also
      indicate that, on nanosecond time scales, pressure makes the local potential less
      steep, contrary to picosecond time scales. Further examination of the QHA
      indicates the nanosecond pressure response may originate at picosecond time
      scales at the exterior of the protein, which suggests that protein-water
      interactions may be involved. The results may lead to understanding adaptations
      in enzymes made by piezophiles that enable them to function at higher pressures.

PMID- 29370704
TI  - Changes for Volume 81.

PMID- 29370702
TI  - Discovery and Preclinical Development of IIIM-290, an Orally Active Potent Cyclin
      Dependent Kinase Inhibitor.
AB  - Rohitukine (1), a chromone alkaloid isolated from Indian medicinal plant
      Dysoxylum binectariferum, has inspired the discovery of flavopiridol and
      riviciclib, both of which are bioavailable only via intravenous route. With the
      objective to address the oral bioavailability issue of this scaffold, four series
      of rohitukine derivatives were prepared and screened for Cdk inhibition and
      cellular antiproliferative activity. The 2,6-dichloro-styryl derivative IIIM-290
      (11d) showed strong inhibition of Cdk-9/T1 (IC50 1.9 nM) kinase and Molt
      4/MIAPaCa-2 cell growth (GI50 < 1.0 MUM) and was found to be highly selective for
      cancer cells over normal fibroblast cells. It inhibited the cell growth of
      MIAPaCa-2 cells via caspase-dependent apoptosis. It achieved 71% oral
      bioavailability with in vivo efficacy in pancreatic, colon, and leukemia
      xenografts at 50 mg/kg, po. It did not have CYP/efflux-pump liability, was not
      mutagenic/genotoxic or cardiotoxic, and was metabolically stable. The preclinical
      data presented herein indicates the potential of 11d for advancement in clinical
      studies.

PMID- 29370705
TI  - An Exciting Year Ahead for ACS Sensors.

PMID- 29370707
TI  - Effect of newborn's admission to intensive care unit on "quality of life" of
      mother: an Indian perspective.
AB  - BACKGROUND: Newborn hospitalized in the neonatal intensive care unit (NICU)
      raises a mother's risk of reduced health-related quality of life (QoL). We
      explored the contributors inducing stress among mothers related to NICU.
      METHODOLOGY: One hundred thirty-five mothers, whose newborn has completed 48
      hours of NICU stay, were interviewed using parental stress scale: neonatal
      intensive care unit and SF-36 health survey questionnaire for further assessment.
      RESULTS: The look and behavior of the baby were predominant contributor to the
      decreased QoL among mothers (p= <.001). A moderate negative association between
      parental stresses related to the NICU environment and their QoL rho = -.467 was
      observed. CONCLUSION: It is required to look back at the interiors of the
      Intensive Care Unit (ICU), the duration provided for the mother and child's
      physical bonding, the unnecessary noise of the alarms and the jungle of wires
      around the baby to optimize the QoL of mothers. The further policy requires
      focusing on building a relation of the mother and child, especially when a child
      needs supportive care.

PMID- 29370708
TI  - Amendment on the findings of two previously published articles.

PMID- 29370709
TI  - The Young Community of the European Association of Preventive Cardiology: The
      future in motion.

PMID- 29370710
TI  - Detection of glucose metabolism disorders in coronary patients enrolled in
      cardiac rehabilitation: Is glycated haemoglobin useful? Data from the prospective
      REHABDIAB study.
AB  - Introduction Diabetes and pre-diabetes are highly prevalent in patients with a
      history of acute coronary syndrome. This is why screening for glucose metabolism
      disorders is recommended in patients following an acute coronary syndrome. The
      aim of our study was to determine whether glycated haemoglobin alone compared
      with the oral glucose tolerance test could allow effective screening for glucose
      metabolism disorders in acute coronary syndrome patients undergoing cardiac
      rehabilitation. Patients and methods Among 347 patients with a recent history of
      acute coronary syndrome enrolled in our cardiac rehabilitation centre, 267
      patients without previously known diabetes were recruited for this prospective
      study with performance of both oral glucose tolerance test and glycated
      haemoglobin measurement. The patients were divided into three groups: newly
      diagnosed diabetes mellitus, pre-diabetes and normoglycaemia according to the
      oral glucose tolerance test and glycated haemoglobin results. The results
      obtained with glycated haemoglobin were compared with those obtained with the
      oral glucose tolerance test, considered as the reference. Results For the
      diagnosis of diabetes, glycated haemoglobin had a sensitivity of 72% and a
      specificity of 100%. Positive and negative predictive values were high at 100%
      and 96%, respectively. However, for the diagnosis of pre-diabetes the sensitivity
      of glycated haemoglobin was low at 64% as were the specificity (53%) and the
      positive predictive values (37%). Glycated haemoglobin overdiagnosed pre-diabetes
      (52% vs 30%, p < 0.0001). For the diagnosis of normoglycaemia, the sensitivity of
      glycated haemoglobin was also low (48%). Conclusion According to our study,
      glycated haemoglobin has low sensitivity and specificity for the detection of pre
      diabetes in patients with coronary disease enrolled in cardiac rehabilitation,
      and glycated haemoglobin over-diagnoses pre-diabetes in comparison with the oral
      glucose tolerance test.

PMID- 29370711
TI  - Magnetic nanoparticles: recent developments in drug delivery system.
AB  - Nanostructured functional materials have demonstrated their great potentials in
      medical applications, attracting increasing attention because of the
      opportunities in cancer therapy and the treatment of other ailments. This article
      reviews the problems and recent advances in the development of magnetic NPs for
      drug delivery.

PMID- 29370712
TI  - Effect of preeclampsia on human milk cytokine levels.
AB  - INTRODUCTION: Preeclampsia (PE) is a systemic inflammatory disease, and its
      effect on human milk immune components is poorly understood. OBJECTIVE: To
      investigate whether PE affects human milk cytokine levels. METHODS: This was a
      prospective observational study involving mothers diagnosed with PE and with
      singleton pregnancy with no fetal malformation. The following cases were
      excluded: diabetes, chorioamnionitis, use of illicit drugs and alcohol, mastitis
      and congenital infection. In total, 228 mothers were studied and divided into two
      groups matched by gestational age: PE (n = 114) and normotensive (control, n =
      114). Colostrum was collected from 24-72 hours postpartum, and mature milk was
      collected at the end of the first month. Cytokines (IL-1beta, IL-6, IL-8, IL-10,
      IL-12, and TNF-alpha) were measured using flow cytometry. A generalized linear
      model with a gamma distribution was used to analyze the differences between
      groups versus time interaction. RESULTS: The mean gestational age was 36 weeks.
      Increased IL-1 and IL-6 levels and reduced IL-12 levels in the colostrum were
      detected in PE, while in the mature milk, the IL-6 and IL-8 levels were lower
      than those of the control group. CONCLUSIONS: PE is associated with increased
      levels of inflammatory cytokines in colostrum and decreased levels in mature
      milk.

PMID- 29370713
TI  - Dynamic viscoelasticity of protease-treated rice batters for gluten-free rice
      bread making.
AB  - Papain (cysteine protease), subtilisin (Protin SD-AY10, serine protease), and
      bacillolysin (Protin SD-NY10, metallo protease) increased the specific volume of
      gluten-free rice breads by 19-63% compared to untreated bread. In contrast,
      Newlase F (aspartyl protease) did not expand the volume of the rice bread. In a
      rheological analysis, the viscoelastic properties of the gluten-free rice batters
      also depended on the protease categories. Principal component analysis (PCA)
      analysis suggested that the storage and loss moduli (G' and G", respectively) at
      35  degrees C, and the maximum values of G' and G", were important factors in the
      volume expansion. Judging from the PCA of the viscoelastic parameters of the rice
      batters, papain and Protin SD-AY10 improved the viscoelasticity for gluten-free
      rice bread making, and Protin SD-NY effectively expanded the gluten-free rice
      bread. The rheological properties differed between Protin SD-NY and the other
      protease treatments.

PMID- 29370714
TI  - How much confidence do we need in animal experiments? Statistical assumptions in
      sample size estimation.
AB  - Statistical sample size calculation is a crucial part of planning nonhuman animal
      experiments in basic medical research. The 3R principle intends to reduce the
      number of animals to a sufficient minimum. When planning experiments, one may
      consider the impact of less rigorous assumptions during sample size determination
      as it might result in a considerable reduction in the number of required animals.
      Sample size calculations conducted for 111 biometrical reports were repeated. The
      original effect size assumptions remained unchanged, but the basic properties
      (type 1 error 5%, two-sided hypothesis, 80% power) were varied. The analyses
      showed that a less rigorous assumption on the type 1 error level (one-sided 5%
      instead of two-sided 5%) was associated with a savings potential of 14% regarding
      the original number of required animals. Animal experiments are predominantly
      exploratory studies. In light of the demonstrated potential reduction in the
      numbers of required animals, researchers should discuss whether less rigorous
      assumptions during the process of sample size calculation may be reasonable for
      the purpose of optimizing the number of animals in experiments according to the
      3R principle.

PMID- 29370715
TI  - Effect of cadence on volume and myoelectric activity during agonist-antagonist
      paired sets (supersets) in the lower body.
AB  - The aim of this study was to investigate the effect of cadence on volume load
      (VLoad) and muscle activity during agonist -antagonist paired sets (APS) in the
      lower body. Twelve trained men (24.0 +/- 3.3 years; 78.3 +/- 9.7 kg; 1.77 +/-
      0.58 m) volunteered to participate in this study. After the 10 maximum repetition
      test for leg extension and seated leg curl, participants performed three
      experimental protocols: first protocol (traditional)-three sets of only leg
      extension (60 bpm); second protocol (fast cadence)-three sets of leg extension,
      with each set preceded by one set on the seated leg curl with fast cadence (90
      bpm); third protocol (slow cadence)-similar to the second, but seated leg curl
      with slow cadence (40 bpm). The total number of repetitions, VLoad and the
      electromyography activity for the vastus lateralis, vastus medialis and rectus
      femoris muscles were recorded. The VLoad was higher during APS than the
      traditional method, but the cadence (fast or slow) of antagonist exercise did not
      influence VLoad. Muscle activity of vastus lateralis was higher during
      traditional protocol; on the other hand, rectus femoris showed higher activity on
      APS fast cadence protocol, indicating that APS has a different influence on
      quadriceps components.

PMID- 29370716
TI  - Helios: History and Anatomy of a Successful In-House Enterprise High-Throughput
      Screening and Profiling Data Analysis System.
AB  - We describe the main characteristics of the Novartis Helios data analysis
      software system (Novartis, Basel, Switzerland) for plate-based screening and
      profiling assays, which was designed and built about 11 years ago. It has been in
      productive use for more than 10 years and is one of the important standard
      software applications running for a large user community at all Novartis
      Institutes for BioMedical Research sites globally. A high degree of automation is
      reached by embedding the data analysis capabilities into a software ecosystem
      that deals with the management of samples, plates, and result data files,
      including automated data loading. The application provides a series of analytical
      procedures, ranging from very simple to advanced, which can easily be assembled
      by users in very flexible ways. This also includes the automatic derivation of a
      large set of quality control (QC) characteristics at every step. Any of the raw,
      intermediate, and final results and QC-relevant quantities can be easily explored
      through linked visualizations. Links to global assay metadata management, data
      warehouses, and an electronic lab notebook system are in place. Automated
      transfer of relevant data to data warehouses and electronic lab notebook systems
      are also implemented.

PMID- 29370717
TI  - Chemical constituents of Brazilian Propolis from the state of Bahia and their
      growth inhibitory activities against cancer cells.
AB  - A novel 2-phenoxychromone (1) and five known flavones (2-6) were isolated from
      northeastern Brazilian propolis in the state of Bahia. The chemical structures of
      these six compounds were determined by spectroscopic investigations and single
      crystal X-ray analysis. The isolated compounds showed growth-inhibitory
      activities, in varying degrees, against human tumor cell lines. This is the first
      report on the discovery of a novel 2-phenoxychromone from propolis.

PMID- 29370719
TI  - Immunization with dendritic cell-based DNA vaccine pRSC-NLDC145.gD-IL21 protects
      mice against herpes simplex virus keratitis.
AB  - AIM: The aim of this study is to investigate the effects of constructed dendritic
      cell (DC)-based DNA vaccine (pRSC-NLDC145.gD-IL21) carried by chitosan
      nanoparticle in preventing primary or recurrent herpes simplex virus keratitis
      (HSK) in mice. METHODS: The expression of constructed plasmid 'pRSC-NLDC145.gD
      IL21' was verified by western blot and immunofluorescence. Plasmids that were
      embedded in chitosan were inoculated to test its therapeutic effect against
      primary or recurrent HSK in mice. Humoral and cellular immune response, clinical
      scores of herpes keratitis and inflammatory infiltration were measured. RESULTS:
      The expressed glycoprotein D (gD) of pRSC-NLDC145.gD-IL21 DNA/chitosan
      nanoparticle vaccine could effectively target corneal DCs and significantly
      alleviate the symptoms of both primary and recurrent HSK mice via eliciting
      strong humoral and cellular immune response. CONCLUSION: Our data suggested that
      DC-based DNA vaccine could be a better choice for HSK treatment in the future.

PMID- 29370720
TI  - Immune modulation by apoptotic dental pulp stem cells in vivo.
AB  - Mesenchymal stem cells (MSCs) show considerable promise as a cellular
      immunotherapy for the treatment of a number of autoimmune and inflammatory
      disorders. However, the precise physiologically and therapeutically relevant
      mechanism(s) by which MSCs mediate immune modulation remains elusive. Dental pulp
      stem cells are a readily available source of MSCs that have been reported to show
      similar immune modulation in vitro as bone marrow MSCs. To test their potential
      in vivo, we used a clinically relevant humanized mouse model of GvHD in which
      only human T cells engraft. In this model, we found no effects on either T-cell
      proliferation, T-cell phenotype or disease progression. To determine if this lack
      of efficacy was related to a failure of engraftment or persistence of the cells,
      we used viability dependent radioactive cell tracking and showed that no cells
      were detectable after 24-h postinjection. Given the apparent failure of MSC to
      survive following intravenous injection, we hypothesized that their apoptosis may
      account for the widely reported therapeutic effect in numerous experimental
      models in vivo. To address this, we employed a well-established model of allergic
      airway inflammation to compare the efficacy of live and apoptotic MSCs in a fully
      immunocompetent model. In this model, both live and apoptotic dental pulp MSCs
      induced a robust immune suppressive reaction that was substantially greater with
      apoptotic cells. We propose that the mechanism of immune modulation following
      systemic application of MSCs is a result of cell entrapment and apoptosis
      occurring in the lungs.

PMID- 29370721
TI  - Intratumoral administration of IL2- and TNF-based fusion proteins cures cancer
      without establishing protective immunity.
AB  - AIM: The combination of tumor-targeting IL2- and TNF-based antibody-cytokine
      fusions has exhibited encouraging results in mouse and men. Here, we studied
      their combination to assess efficacy and mechanism of action in four different
      immunocompetent mouse models of cancer. METHODS: Mice receiving a single
      intratumoral injection of F8-IL2, F8-TNF or the combination were investigated for
      tumor-infiltrating leukocytes and rechallenged when cured. RESULTS: In three
      models, a proportion of treated animals could be cured, most probably by
      infiltrating NK and CD8+ T cells. Most of the cured mice did not acquire
      protective immunity when rechallenged with the same tumor cell line. CONCLUSION:
      Immunocompetent mouse tumor models may not be adequate enough to predict the
      search for more efficacious therapy regimens.

PMID- 29370722
TI  - Immunotherapy using regulatory T cells in cancer suggests more flavors of
      hypersensitivity type IV.
AB  - Regulatory T cells (Tregs) profoundly affect tumor microenvironment and exert
      dominant suppression over antitumor immunity in response to self-antigen
      expressed by tumor. Immunotherapy targeting Tregs lead to a significant
      improvement in antitumor immunity. Intradermal injection of tumor antigen results
      in negative delayed-type hypersensitivity (DTH) type IV. However, anti-Tregs
      treatment/use of adjuvant along with tumor antigens turns DTH to positive.
      Considering Tregs as the earliest tumor sensor/responders, tumor can be regarded
      as Treg-mediated type IV hypersensitivity and negative DTH to tumor antigen is
      due to anti-inflammatory action of Tregs to tumor antigens at the injection site.
      Such a view would help us in basic and clinical situations to testify a candidate
      vaccine via dermal administration and evaluation of Treg proportion at injection
      site.

PMID- 29370723
TI  - Isolated immune-related pancreatic exocrine insufficiency associated with
      pembrolizumab therapy.
AB  - We report a case of isolated immune-related pancreatic exocrine insufficiency in
      a patient treated with pembrolizumab for metastatic melanoma. This patient
      presented with explosive diarrhea and was treated with high dose corticosteroids
      for possible immune-related colitis. However, biopsies from colon and duodenum
      did not show any histological evidence of colitis/enteritis. Serum amylase and
      lipase were not elevated. There was no evidence of pancreatitis or pancreatic
      metastases on imaging. Significantly lower fecal elastase test on two occasions
      confirmed the diagnosis of pancreatic exocrine insufficiency. He was treated with
      pancreatic enzyme supplementation with complete resolution of diarrhea. This case
      reinforces the importance of awareness and anticipation of unusual immune-related
      adverse events related to checkpoint inhibitors.

PMID- 29370724
TI  - Do immune checkpoint inhibitors increase sensitivity to salvage chemotherapy?

PMID- 29370725
TI  - Pooled in vivo screens for cancer immunotherapy target discovery.

PMID- 29370726
TI  - Cancer immunotherapy using tumor antigen-reactive T cells.
AB  - Studies over the last 30 years have shown the promise of cancer immunotherapy
      using T cells. In particular, since the report by Rosenberg and colleagues in
      2002 that adoptive T-cell therapy (ACT) under lymphopenic conditions
      substantially increased response rates in melanoma patients, ACT has become a
      promising immunotherapeutic route to cancer treatment. Here we provide a brief
      history of ACT and review the characteristics of T-cell therapeutics that are
      specific to this approach. Since every T-cell treatment has its own unique
      properties in terms of number and type of target antigens, and number of epitopes
      and type of T cells, we review the main strategies for designing ACT: how Ag
      specificity is determined, how is it standardized and the need for
      lymphodepletion to induce epitope spreading. We also briefly consider the next
      generation of ACT.

PMID- 29370727
TI  - Chimeric antigen receptor T-cell therapy for cancer: a basic research-oriented
      perspective.
AB  - Chimeric antigen receptor (CAR) T cells have outstanding therapeutic potential
      for treating blood cancers. The prospects for this technology have accelerated
      basic research, clinical translation and Big Pharma's investment in the field of
      T-cell therapeutics. This interest has led to the discovery of key factors that
      affect CAR T-cell efficacy and play pivotal roles in T-cell immunology. Herein,
      we introduce advances in adoptive immunotherapy and the birth of CAR T cells, and
      review CAR T-cell studies that focus on three important features: CAR constructs,
      target antigens and T-cell phenotypes. At last, we highlight novel strategies
      that overcome the tumor microenvironment and circumvent CAR T-cell side effects,
      and consider the future direction of CAR T-cell development.

PMID- 29370728
TI  - Feature Extraction with GMDH-Type Neural Networks for EEG-Based Person
      Identification.
AB  - The brain activity observed on EEG electrodes is influenced by volume conduction
      and functional connectivity of a person performing a task. When the task is a
      biometric test the EEG signals represent the unique "brain print", which is
      defined by the functional connectivity that is represented by the interactions
      between electrodes, whilst the conduction components cause trivial correlations.
      Orthogonalization using autoregressive modeling minimizes the conduction
      components, and then the residuals are related to features correlated with the
      functional connectivity. However, the orthogonalization can be unreliable for
      high-dimensional EEG data. We have found that the dimensionality can be
      significantly reduced if the baselines required for estimating the residuals can
      be modeled by using relevant electrodes. In our approach, the required models are
      learnt by a Group Method of Data Handling (GMDH) algorithm which we have made
      capable of discovering reliable models from multidimensional EEG data. In our
      experiments on the EEG-MMI benchmark data which include 109 participants, the
      proposed method has correctly identified all the subjects and provided a
      statistically significant ([Formula: see text]) improvement of the identification
      accuracy. The experiments have shown that the proposed GMDH method can learn new
      features from multi-electrode EEG data, which are capable to improve the accuracy
      of biometric identification.

PMID- 29370729
TI  - Metaplasticity: A Promising Tool to Disentangle Chronic Disorders of
      Consciousness Differential Diagnosis.
AB  - The extent of cortical reorganization after brain injury in patients with
      Vegetative State/Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious
      State (MCS) depends on the residual capability of modulating synaptic plasticity.
      Neuroplasticity is largely abnormal in patients with UWS, although the fragments
      of cortical activity may exist, while patients MCS show a better cortical
      organization. The aim of this study was to evaluate cortical excitability in
      patients with disorders of consciousness (DoC) using a transcranial direct
      current stimulation (TDCS) metaplasticity protocol. To this end, we tested motor
      evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and
      intracortical facilitation (ICF). These measures were correlated with the level
      of consciousness (by the Coma Recovery Scale-Revised, CRS-R). MEP amplitude,
      SICI, and ICF strength were significantly modulated following different
      metaplasticity TDCS protocols only in the patients with MCS. SICI modulations
      showed a significant correlation with the CRS-R score. Our findings demonstrate,
      for the first time, a partial preservation of metaplasticity properties in some
      patients with DoC, which correlates with the level of awareness. Thus,
      metaplasticity assessment may help the clinician in differentiating the patients
      with DoC, besides the clinical evaluation. Moreover, the responsiveness to
      metaplasticity protocols may identify the subjects who could benefit from
      neuromodulation protocols.

PMID- 29370730
TI  - Shared meanings of success, happiness, and health among adults with cerebral
      palsy and physiotherapists: implications for practice and research.
AB  - PURPOSE: To describe shared meanings of success, happiness, and health of adults
      with cerebral palsy and physiotherapists. MATERIALS AND METHODS: Ethnography
      employed open ended/semi-structured interviews and structured questionnaires
      (Satisfaction with Life Scale, Beck Depression Inventory-II(r), Oxford Happiness
      Questionnaire, Life Habits Questionnaire, Medical Outcomes Study-Social Support
      Survey, and PROMIS(r) Pain Interference Scale). Content analysis of qualitative
      data and principal components analysis of questionnaire responses identified
      shared meanings. RESULTS: Fourteen adults with cerebral palsy and 15
      physiotherapists (median age 46) had similar levels of education. For both
      groups, social achievements, personal goals, employment, and supporting a family
      defined success. Adults with cerebral palsy more frequently identified tenacity
      and persistence as important for success. Both groups described happiness as
      spending time with loved ones, recreational activities, and having purpose in
      life. Adults with cerebral palsy identified the importance of self-acceptance for
      happiness. For both, health included self-care of mind/spirit, cardiovascular and
      musculoskeletal wellness, and physical fitness (the ability to perform physical
      tasks). Analysis of questionnaire responses identified shared meanings
      (eigenvalue 41, 95% explained variance). CONCLUSIONS: Adults with cerebral palsy
      and physiotherapists share similar experiences, behaviors, and feelings about
      success, happiness, and health. This knowledge may improve communication, enhance
      evidence-based practice, and foster services to support wellbeing. Implications
      for rehabilitation Cerebral palsy is a life-long condition, but we know little
      about social and physical outcomes for adults with cerebral palsy. Lack of
      understanding about meanings of success, happiness, and health may be a barrier
      for consumers accessing and for providers delivering evidence-based services.
      Physiotherapists and adults with cerebral palsy share similar meanings (feelings,
      experiences, beliefs, behaviors) of success, happiness, and health- or wellbeing.
      Knowledge of this common ground may result in improved communication between
      providers and consumers, and foster more relevant and meaningful services to
      support the wellbeing of adults with cerebral palsy.

PMID- 29370731
TI  - Possibilities of kinesio taping to prevent injuries of professional dancers.
AB  - A literature review of the application of kinesio taping in the prevention of
      professional dancers' injuries indicated frequent dance-related and overuse
      injuries and a lack of organized information about this issue. This study aimed
      to assess the impact of kinesio taping on the musculoskeletal system of dancers,
      based on scientific research data from 2015-2017. The analysis revealed that
      kinesio taping can effectively reduce muscle spasms, rebuild muscle strength of
      the injured extremity, improve static and dynamic balance and ease pain, due to
      its ability to improve proprioception of joints and regulate muscle tone. These
      effects reduce muscle imbalance and joint instability, thus increasing treatment
      efficacy and shortening the physical load limitation. Kinesio taping
      significantly reduces the risk of overuse syndromes and dance-related injuries
      during dance training and strenuous exercises of people with chronic
      musculoskeletal diseases. Therefore, kinesio taping has broad utility in primary
      and secondary prevention of dance-related injuries.

PMID- 29370732
TI  - Closing the barrier between disease and health outcomes in Africa through
      research and capacity development.
AB  - BACKGROUND: While the burden of disease in Africa is high, health research
      emanating from the continent is low. Building human capacity and research
      infrastructure to close the gap between research and disease is thus of great
      imporatance. OBJECTIVE: In order to improve research outputs and postgraduate
      training in the Faculty of Health Sciences, University of the Witwatersrand, the
      Health Sciences Research Office put in place a series of strategic initiatives
      over time. METHODS: A range of strategic activities, for both postgraduate
      students and academic staff, were developed in parallel and sequentially over a
      period of approximately nine years (2008-2016). The latter years were a time of
      consolidation of the programmes. Outcomes of these activities were 'measured' by
      increases in publications, decreases in time to graduation and enrichment of the
      research environment. RESULTS: A doubling of research publications and an
      increase in citations occurred over the period under review. In addition, there
      was a decrease in the time postgraduate students took to graduate. CONCLUSIONS: A
      varied, but structured research management plan may be of value in African and
      other developing health sciences institutions to enable the increase in research
      outputs and capacity development, desperately needed to close the barrier between
      disease and health.

PMID- 29370733
TI  - Food-derived regulatory factors against obesity and metabolic syndrome.
AB  - Obesity is a key factor in metabolic syndrome. The study of metabolic syndrome
      focuses on the anti-weight gain properties of physiological mechanisms and food
      components. Abnormal energy metabolism is a major risk factor of metabolic
      syndrome. Chronic inflammation is a feature of obesity; cytokines from
      hypertrophied adipocytes cause inflammation in both adipose tissue and blood
      vessels, resulting in symptoms of metabolic syndrome. Tumor necrosis factor-alpha
      causes insulin resistance in adipocytes and regression of brown adipocytes,
      resulting in abnormal energy metabolism. Functional foods can serve as a strategy
      for prevention and treatment of obesity linked with metabolic processes in white
      and brown adipose tissues. Diet-induced thermogenesis caused by certain food
      components stimulates burning of stored fat within adipose tissues. A mechanistic
      understanding of dietary thermogenesis via the sympathetic nerve system will
      prove valuable for the development of precise strategies for the practical
      prevention of metabolic syndrome.

PMID- 29370734
TI  - Seasoning ingredients in a medium-fat diet regulate lipid metabolism in
      peripheral tissues via the hypothalamic-pituitary axis in growing rats.
AB  - We fed rats noodle (N) -diet containing 30 wt.% instant noodle with a 26% fat-to
      energy ratio for 30 days (N-group). Compared with rats that were fed the same
      amount of nutrients (C-group), the N-group showed lower liver triacylglycerol
      levels and higher fecal cholesterol levels. We then analyzed transcriptome of the
      hypothalamic-pituitary (HP), the liver and the white adipose tissue (WAT).
      Thyroid stimulating hormone (Tshb), and its partner, glycoprotein hormone genes
      were up-regulated in the HP of N-group. Sterol regulatory element binding
      transcription factors were activated in the liver of N-group, while an up
      regulation of the angiogenic signal occurred in the WAT of N-group. N-group
      showed higher urine noradrenaline (NA) level suggesting that these tissue signals
      are regulated by NA and Tshb. The N-diet contains 0.326 wt.% glutamate, 0.00236
      wt.% 6-shogaol and Maillard reaction products. Our results suggest that these
      ingredients may affect lipid homeostasis via the HP axis.

PMID- 29370735
TI  - Creating a Faculty Publications Database Using Sci-Matetm.
AB  - Faculty publication are reflection of research activity at a medical school and
      are thus very important. When a more organized and detailed record of faculty
      productivity was desired at the University of Nevada School of Medicine, manual
      methods as well as generic database manger were seen as too cumbersome. Instead,
      automating the collection using Sci-Mate, tm since it will accept downloaded
      citations, was seen as the more efficient solution to producing and keeping eh
      list up-to-date. This article will discuss the design and the methods used to
      create the database.

PMID- 29370736
TI  - The Faculty Research Interests Roster.
AB  - Profiles of the research interests of faculty at Thomas Jefferson University
      (TJU) were gathered and organized into the three-part faculty research interests
      roster. Faculty completed a questionnaire detailing their current research
      activities and areas of technical expertise. The article describe difficulties
      encountered in gathering and organizing the information. Two editions of the
      Roster were complied. The second, revised edition consists of section listing
      faculty by department with their research interests as they describe them, by
      broader subject arrangement, and by areas of technical expertise. The article
      concludes wit the description of the positive and negative results generated by
      the Roster and a plan for improving the publication in the future.

PMID- 29370737
TI  - DIOGENES.
AB  - This paper describes the DIOGENES database available though BRS Information
      Technologies. The database focuses on drug and medical device regulatory
      information from the Food and Drug Administration. The specific strengths of
      DIOGENES are mentioned as well as some plans for further development of the
      database.

PMID- 29370740
TI  - Letter to the Editor.
AB  - No abstract available for this article.

PMID- 29370739
TI  - CD-ROM.
AB  - What makes CD-ROM attractive or unattractive in the library setting? What are its
      advantages or disadvantages? How will the technology develop? What has been the
      experience of libraries who have tested and introduced CD-ROM products to their
      users? The following two-part article addresses these questions. Part 1 explores
      the development of disk technology, its advantages and disadvantages and
      potential library applications. The actual testing and use of one of the CD-ROM
      products, PsycLIT, is the focus of Part II.

PMID- 29370742
TI  - Creating Education Programs in Libraries.
AB  - No abstract available for this article.

PMID- 29370743
TI  - Sharewars.
AB  - No abstract available for this article.

PMID- 29370744
TI  - Protocol for a cluster randomised controlled trial on information technology
      enabled nutrition intervention among urban adults in Chandigarh (India): SMART
      eating trial.
AB  - Nutrition is an important determinant of health. At present, nutrition programs
      in India mainly emphasize improving maternal and child nutrition. Adult nutrition
      has not received due attention, though diseases like hypertension and diabetes
      are largely preventable through changes in dietary and physical activity
      behaviour. Little is known about the best approaches to improve dietary
      behaviours, especially the role of modern information technology (IT) in health
      education. We describe the protocol of the SMART Eating (Small, Measurable and
      Achievable dietary changes by Reducing fat, sugar and salt consumption and Trying
      different fruits and vegetables) health promotion intervention. A Cluster
      Randomised Controlled Trial will evaluate the effect of an IT-enabled
      intervention on nutrition behaviour among urban adults of Chandigarh, India.
      Formative research using a qualitative exploratory approach was undertaken to
      inform the intervention. The IT-enabled intervention programme includes website
      development, Short Message Service (SMS), e-mail reminders and interactive help
      by mobile and landline phones. The IT-enabled intervention will be compared to
      the traditional nutrition education program of distributing pamphlets in the
      control group. The primary outcome will be the percentage of study participants
      meeting the dietary intake guidelines of the National Institute of Nutrition,
      Hyderabad, India and the change in intake of fat, sugar, salt, fruit and
      vegetables after the intervention. The difference in differences method will be
      used to determine the net change in dietary intakes resulting from the
      interventions. Measurements will be made at baseline and at 6 months post
      intervention, using a food frequency questionnaire. The formative research led to
      the development of a comprehensive intervention, focusing on five dietary
      components and using multi-channel communication approach including the use of IT
      to target urban North Indians from diverse socio-economic backgrounds. The
      Cluster Randomised Controlled Trial design is suitable for evaluating the
      effectiveness of this IT-enabled intervention for dietary behaviour change.

PMID- 29370745
TI  - Design and fabrication of injectable microcarriers composed of acellular
      cartilage matrix and chitosan.
AB  - Cartilage is an avascular tissue with limited self-repair ability. Since the
      methods for treatment of cartilage defects have not been effective, new therapies
      based on tissue engineering are considered over the recent years. In this study,
      human cartilage tissue was decellularized and porous injectable microcarriers
      (MCs) composed of acellular extracellular matrix (ECM) of cartilage tissue and
      chitosan (CS), with different ECM weight ratios, were fabricated by
      electrospraying technique to be used in the treatment of articular cartilage
      defects. Various properties of ECM/CS MCs such as microstructure, mechanical
      strength, water uptake behaviour, and biodegradability rate were investigated.
      MCs with 1% ECM and 2% CS show appropriate characteristics in terms of pore size,
      density, porosity, and mechanical properties. MTT cytotoxicity assays performed
      on chondrocyte cells cultured on ECM/CS MCs with various amounts of ECM showed
      that the sample with 1% ECM content had the greatest cell attachment. Overall, it
      can be concluded that the prepared MCs with 1% ECM could be a potential candidate
      to be used in cartilage tissue engineering applications.

PMID- 29370746
TI  - Preface.

PMID- 29370747
TI  - Editorial: Corticotropin Releasing Factor (CRF) and Its Receptors: From Structure
      to Function in Health and Disease (Part II).

PMID- 29370749
TI  - Intraventricular infusion of clusterin ameliorated cognition and pathology in
      Tg6799 model of Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by the deposition of
      amyloid-beta (Abeta) in brain parenchyma and cerebral blood vessels as cerebral
      amyloid angiopathy (CAA). Clusterin, a chaperon protein associated with Abeta
      aggregation, toxicity and transport through blood-brain barrier, may play a key
      role in the development of AD. Recently, clusterin peptide D-[113-122] was shown
      to mimic clusterin's function and exerted therapeutic effect in atherosclerosis.
      In this study, we investigated whether this clusterin peptide also affected
      (Abeta) deposition in AD transgenic mouse. RESULTS: Using a micropump, synthetic
      peptide 113-122 of clusterin protein (20 MUg/200 MUl) was infused into the
      lateral ventricle of 8-month 5 * FAD transgenic mouse model (Tg6799), for 2
      weeks. Water-maze testing showed an improved cognitive function of the Tg6799
      mice treated with clusterin. Immunocytochemistry and quantitative analysis
      revealed that intraventricular (icv) administration of clusterin peptide in
      Tg6799 mouse reduced Abeta plaques as well the severity of cerebral amyloid
      angiopathy. Enzyme-linked immunosorbent assay demonstrated a decreased in the
      soluble levels of Abeta (Abeta40 and Abeta42) in the brain. Western-blot revealed
      an increased level of LRP-2 after clusterin peptide treatment. CONCLUSION: These
      results suggest that icv infusion of clusterin peptide D-[113-122] offers a
      promising therapeutic approach to reduce Abeta deposition as well as CAA. The
      LRP2-mediated clearance system might be involved in the mechanism of these
      effects.

PMID- 29370750
TI  - CONFOLD2: improved contact-driven ab initio protein structure modeling.
AB  - BACKGROUND: Contact-guided protein structure prediction methods are becoming more
      and more successful because of the latest advances in residue-residue contact
      prediction. To support contact-driven structure prediction, effective tools that
      can quickly build tertiary structural models of good quality from predicted
      contacts need to be developed. RESULTS: We develop an improved contact-driven
      protein modelling method, CONFOLD2, and study how it may be effectively used for
      ab initio protein structure prediction with predicted contacts as input. It
      builds models using various subsets of input contacts to explore the fold space
      under the guidance of a soft square energy function, and then clusters the models
      to obtain the top five models. CONFOLD2 obtains an average reconstruction
      accuracy of 0.57 TM-score for the 150 proteins in the PSICOV contact prediction
      dataset. When benchmarked on the CASP11 contacts predicted using CONSIP2 and
      CASP12 contacts predicted using Raptor-X, CONFOLD2 achieves a mean TM-score of
      0.41 on both datasets. CONCLUSION: CONFOLD2 allows to quickly generate top five
      structural models for a protein sequence when its secondary structures and
      contacts predictions at hand. The source code of CONFOLD2 is publicly available
      at https://github.com/multicom-toolbox/CONFOLD2/ .

PMID- 29370748
TI  - A SNP panel for identification of DNA and RNA specimens.
AB  - BACKGROUND: SNP panels that uniquely identify an individual are useful for
      genetic and forensic research. Previously recommended SNP panels are based on DNA
      profiles and mostly contain intragenic SNPs. With the increasing interest in RNA
      expression profiles, we aimed for establishing a SNP panel for both DNA and RNA
      based genotyping. RESULTS: To determine a small set of SNPs with maximally
      discriminative power, genotype calls were obtained from DNA and blood-derived RNA
      sequencing data belonging to healthy, geographically dispersed, Dutch
      individuals. SNPs were selected based on different criteria like genotype call
      rate, minor allele frequency, Hardy-Weinberg equilibrium and linkage
      disequilibrium. A panel of 50 SNPs was sufficient to identify an individual
      uniquely: the probability of identity was 6.9 * 10- 20 when assuming no family
      relations and 1.2 * 10- 10 when accounting for the presence of full sibs. The
      ability of the SNP panel to uniquely identify individuals on DNA and RNA level
      was validated in an independent population dataset. The panel is applicable to
      individuals from European descent, with slightly lower power in non-Europeans.
      Whereas most of the genes containing the 50 SNPs are expressed in various
      tissues, our SNP panel needs optimization for other tissues than blood.
      CONCLUSIONS: This first DNA/RNA SNP panel will be useful to identify sample mix
      ups in biomedical research and for assigning DNA and RNA stains in crime scenes
      to unique individuals.

PMID- 29370751
TI  - Association mapping for total polyphenol content, total flavonoid content and
      antioxidant activity in barley.
AB  - BACKGROUND: The interest has been increasing on the phenolic compounds in plants
      because of their nutritive function as food and the roles regulating plant
      growth. However, their underlying genetic mechanism in barley is still not clear.
      RESULTS: A genome-wide association study (GWAS) was conducted for total phenolic
      content (TPC), total flavonoid content (FLC) and antioxidant activity (AOA) in 67
      cultivated and 156 Tibetan wild barley genotypes. Most markers associated with
      phenolic content were different in cultivated and wild barleys. The markers bPb
      0572 and bPb-4531 were identified as the major QTLs controlling phenolic
      compounds in Tibetan wild barley. Moreover, the marker bPb-4531 was co-located
      with the UDP- glycosyltransferase gene (HvUGT), which is a homolog to Arabidopsis
      UGTs and involved in biosynthesis of flavonoid glycosides . CONCLUSIONS: GWAS is
      an efficient tool for exploring the genetic architecture of phenolic compounds in
      the cultivated and Tibetan wild barleys. The DArT markers applied in this study
      can be used in barley breeding for developing new barley cultivars with higher
      phenolics content. The candidate gene (HvUGT) provides a potential route for deep
      understanding of the molecular mechanism of flavonoid synthesis.

PMID- 29370752
TI  - The pivotal role of aristaless in development and evolution of diverse antennal
      morphologies in moths and butterflies.
AB  - BACKGROUND: Antennae are multi-segmented appendages and main odor-sensing organs
      in insects. In Lepidoptera (moths and butterflies), antennal morphologies have
      diversified according to their ecological requirements. While diurnal butterflies
      have simple, rod-shaped antennae, nocturnal moths have antennae with protrusions
      or lateral branches on each antennal segment for high-sensitive pheromone
      detection. A previous study on the Bombyx mori (silk moth) antenna, forming two
      lateral branches per segment, during metamorphosis has revealed the dramatic
      change in expression of antennal patterning genes to segmentally reiterated,
      branch-associated pattern and abundant proliferation of cells contributing almost
      all the dorsal half of the lateral branch. Thus, localized cell proliferation
      possibly controlled by the branch-associated expression of antennal patterning
      genes is implicated in lateral branch formation. Yet, actual gene function in
      lateral branch formation in Bombyx mori and evolutionary mechanism of various
      antennal morphologies in Lepidoptera remain elusive. RESULTS: We investigated the
      function of several genes and signaling specifically in lateral branch formation
      in Bombyx mori by the electroporation-mediated incorporation of siRNAs or
      morpholino oligomers. Knock down of aristaless, a homeobox gene expressed
      specifically in the region of abundant cell proliferation within each antennal
      segment, during metamorphosis resulted in missing or substantial shortening of
      lateral branches, indicating its importance for lateral branch formation.
      aristaless expression during metamorphosis was lost by knock down of Distal-less
      and WNT signaling but derepressed by knock down of Notch signaling, suggesting
      the strict determination of the aristaless expression domain within each antennal
      segment by the combinatorial action of them. In addition, analyses of pupal
      aristaless expression in antennae with various morphologies of several
      lepidopteran species revealed that the aristaless expression pattern has a
      striking correlation with antennal shapes, whereas the segmentally reiterated
      expression pattern was observed irrespective of antennal morphologies.
      CONCLUSIONS: Our results presented here indicate the significance of aristaless
      function in lateral branch formation in B. mori and imply that the
      diversification in the aristaless expression pattern within each antennal segment
      during metamorphosis is one of the significant determinants of antennal
      morphologies. According to these findings, we propose a mechanism underlying
      development and evolution of lepidopteran antennae with various morphologies.

PMID- 29370753
TI  - Genome-wide association analysis and QTL mapping reveal the genetic control of
      cadmium accumulation in maize leaf.
AB  - BACKGROUND: Accumulation of cadmium (Cd) in maize (Zea mays L.) poses a
      significant risk to human health as it is ingested via the food chain. A genome
      wide association study (GWAS) was conducted in a population of 269 maize
      accessions with 43,737 single nucleotide polymorphisms (SNPs) to identify
      candidate genes and favorable alleles for controlling Cd accumulation in maize.
      RESULTS: When grown in contaminated soil, accessions varied significantly in leaf
      Cd concentration at both the seeding and maturing stages with phenotypic
      variation and the coefficient of variation all above 48%. The co-localized region
      between SYN27837 (147,034,650 bp) and SYN36598 (168,551,327 bp) on chromosome 2
      was associated with leaf Cd under three soil conditions varying in Cd content in
      2015 and 2016. The significant SNP (SYN25051) at position 161,275,547 could
      explained 27.1% of the phenotype variation. Through QTL mapping using the
      IBMSyn10 double haploid (DH) population, we validated the existence of a major
      QTL identified by GWAS; qLCd2 could explain the 39.8% average phenotype variation
      across the experiments. Expression of GRMZM2G175576 encoding a cadmium/zinc
      transporting ATPase underlying the QTL was significantly increased in roots,
      stems and leaves of B73, a low Cd accumulation line in response to Cd stress.
      CONCLUSIONS: Our findings provide new insights into the genetic control of Cd
      accumulation and could aid rapid development of maize genotypes with low-Cd
      accumulation by manipulation of the favorable alleles.

PMID- 29370754
TI  - Cardiac valve calcification and risk of cardiovascular or all-cause mortality in
      dialysis patients: a meta-analysis.
AB  - BACKGROUND: Vascular calcification is a risk factor for the pathogenesis of
      cardiovascular disease and mortality in dialysis patients. Nevertheless, the
      association between cardiac valve calcification (CVC) and the outcome of dialysis
      is still illusive. The purpose of this meta-analysis is to evaluate the
      association between theCVC and cardiovascular or all-cause mortality in dialysis
      patients. METHODS: Literatures involving the baseline CVC and cardiovascular or
      all-cause mortality in dialysis patients were searchedfrom the PubMed, Embase, as
      well as two Chinese databases (i.e. Wanfang and CNKI databases). Articles
      published before November 2016were eligible to the study. RESULTS: Ten studies
      involving 2686 participants were included. CVC was correlated with increased risk
      of cardiovascular mortality (hazard risk [HR]: 2.81; 95% confidence intervals
      [CI]: 1.92-4.10) and all-cause mortality (HR: 1.73; 95% CI: 1.42-2.11). Subgroup
      analysis showed an excess risk of all-cause mortality (HR: 1.35; 95% CI: 1.02
      1.79) among patients with one CVC, and increased risk of all-cause mortality in
      patients with two CVCs (HR 2.15; 95% CI 1.57-2.94). CONCLUSIONS: CVC is
      correlated with higher cardiovascular and all-cause mortality risk in dialysis
      patients. Regular follow-up monitoring of CVC may be helpful for risk
      stratification of patients underwent dialysis.

PMID- 29370755
TI  - Associations between intraoperative ventilator settings during one-lung
      ventilation and postoperative pulmonary complications: a prospective
      observational study.
AB  - BACKGROUND: The interest in perioperative lung protective ventilation has been
      increasing. However, optimal management during one-lung ventilation (OLV) remains
      undetermined, which not only includes tidal volume (VT) and positive end
      expiratory pressure (PEEP) but also inspired oxygen fraction (FIO2). We aimed to
      investigate current practice of intraoperative ventilation during OLV, and
      analyze whether the intraoperative ventilator settings are associated with
      postoperative pulmonary complications (PPCs) after thoracic surgery. METHODS: We
      performed a prospective observational two-center study in Japan. Patients
      scheduled for thoracic surgery with OLV from April to October 2014 were eligible.
      We recorded ventilator settings (FIO2, VT, driving pressure (DeltaP), and PEEP)
      and calculated the time-weighted average (TWA) of ventilator settings for the
      first 2 h of OLV. PPCs occurring within 7 days of thoracotomy were investigated.
      Associations between ventilator settings and the incidence of PPCs were examined
      by multivariate logistic regression. RESULTS: We analyzed perioperative
      information, including preoperative characteristics, ventilator settings, and
      details of surgery and anesthesia in 197 patients. Pressure control ventilation
      was utilized in most cases (92%). As an initial setting for OLV, an FIO2 of 1.0
      was selected for more than 60% of all patients. Throughout OLV, the median TWA
      FIO2 of 0.8 (0.65-0.94), VT of 6.1 (5.3-7.0) ml/kg, DeltaP of 17 (15-20) cm H2O,
      and PEEP of 4 (4-5) cm H2O was applied. Incidence rate of PPCs was 25.9%, and
      FIO2 was independently associated with the occurrence of PPCs in multivariate
      logistic regression. The adjusted odds ratio per FIO2 increase of 0.1 was 1.30
      (95% confidence interval: 1.04-1.65, P = 0.0195). CONCLUSIONS: High FIO2 was
      applied to the majority of patients during OLV, whereas low VT and slight degree
      of PEEP were commonly used in our survey. Our findings suggested that a higher
      FIO2 during OLV could be associated with increased incidence of PPCs.

PMID- 29370756
TI  - Centre- versus home-based exercise among people with mci and mild dementia: study
      protocol for a randomized parallel-group trial.
AB  - BACKGROUND: Worldwide, almost 50million people lived with dementia in 2016. A
      cure or disease modifying pharmaceutical treatment for dementia remains elusive
      so alternative therapies are of critical importance. Mounting evidence supports
      exercise in the prevention and therapy of dementia. However, the cognitive,
      physical, and psychological challenges common to dementia along with a poor
      understanding and accommodation of dementia in the community are major barriers
      to exercise. Consequently, effective delivery options need to be identified. The
      primary objective of this study is to compare the effectiveness of center-based
      (CB) exercise versus home-based (HB) exercise for achievement of physical
      activity guidelines among people with MCI or mild dementia. METHODS: This is a
      randomized parallel-group trial comparing the effects of CB and HB exercise
      adherence among community-dwelling adults >=50 years with a clinical diagnosis of
      MCI or mild dementia. Participants will be randomized to either CB or HB
      exercise. The CB group will meet weekly for small group exercise and will be
      prescribed additional exercise to be completed independently. Participants in the
      HB group will be given a physical activity prescription to be completed
      independently in the community. Participants in HB will also be contacted by
      phone monthly to adjust exercise prescriptions. The primary outcome will be
      achievement of exercise guidelines (150 min/wk. of moderate activity) assessed
      using an activity monitor. Secondary objectives will evaluate cost-effectiveness
      and the influence of individual and environmental factors on the primary outcome.
      Tertiary outcomes include physical function, cognition, mood, and quality of
      life. DISCUSSION: There is scant research to indicate the most effective way to
      deliver exercise to people with MCI and mild dementia, which is needed
      specifically because these groups face significant barriers to exercise. To
      capitalize on the benefits of exercise, feasible exercise delivery options need
      to be identified. The results of this study will directly complement ongoing
      clinical trials and will be essential to implementing exercise recommendations
      specific to the prevention and therapy of dementia in a feasible and cost
      effective manner when they emerge. TRIAL REGISTRATION: Clinicatrials.gov ;
      Identifier: NCT02774720 (version updated December 12, 2016).

PMID- 29370757
TI  - Expression of two barley proteinase inhibitors in tomato promotes endogenous
      defensive response and enhances resistance to Tuta absoluta.
AB  - BACKGROUND: Plants and insects have coexisted for million years and evolved a set
      of interactions which affect both organisms at different levels. Plants have
      developed various morphological and biochemical adaptations to cope with
      herbivores attacks. However, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae)
      has become the major pest threatening tomato crops worldwide and without the
      appropriated management it can cause production losses between 80 to 100%.
      RESULTS: The aim of this study was to investigate the in vivo effect of a serine
      proteinase inhibitor (BTI-CMe) and a cysteine proteinase inhibitor (Hv-CPI2) from
      barley on this insect and to examine the effect their expression has on tomato
      defensive responses. We found that larvae fed on tomato transgenic plants co
      expressing both proteinase inhibitors showed a notable reduction in weight.
      Moreover, only 56% of these larvae reached the adult stage. The emerged adults
      showed wings deformities and reduced fertility. We also investigated the effect
      of proteinase inhibitors ingestion on the insect digestive enzymes. Our results
      showed a decrease in larval trypsin activity. Transgenes expression had no
      harmful effect on Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae), a predator
      of Tuta absoluta, despite transgenic tomato plants attracted the mirid. We also
      found that barley cystatin expression promoted plant defense by inducing the
      expression of the tomato endogenous wound inducible Proteinase inhibitor 2 (Pin2)
      gene, increasing the production of glandular trichomes and altering the emission
      of volatile organic compounds. CONCLUSION: Our results demonstrate the usefulness
      of the co-expression of different proteinase inhibitors for the enhancement of
      plant resistance to Tuta absoluta.

PMID- 29370758
TI  - Transcriptome sequencing of the human pathogen Corynebacterium diphtheriae NCTC
      13129 provides detailed insights into its transcriptional landscape and into DtxR
      mediated transcriptional regulation.
AB  - BACKGROUND: The human pathogen Corynebacterium diphtheriae is the causative agent
      of diphtheria. In the 1990s a large diphtheria outbreak in Eastern Europe was
      caused by the strain C. diphtheriae NCTC 13129. Although the genome was sequenced
      more than a decade ago, not much is known about its transcriptome. Our aim was to
      use transcriptome sequencing (RNA-Seq) to close this knowledge gap and gain
      insights into the transcriptional landscape of a C. diphtheriae tox+ strain.
      RESULTS: We applied two different RNA-Seq techniques, one to retrieve 5'-ends of
      primary transcripts and the other to characterize the whole transcriptional
      landscape in order to gain insights into various features of the C. diphtheriae
      NCTC 13129 transcriptome. By examining the data we identified 1656 transcription
      start sites (TSS), of which 1202 were assigned to genes and 454 to putative novel
      transcripts. By using the TSS data promoter regions recognized by the
      housekeeping sigma factor sigmaA and its motifs were analyzed in detail,
      revealing a well conserved -10 but an only weakly conserved -35 motif,
      respectively. Furthermore, with the TSS data 5'-UTR lengths were explored. The
      observed 5'-UTRs range from zero length (leaderless transcripts), which make up
      20% of all genes, up to over 450 nt long leaders, which may harbor regulatory
      functions. The C. diphtheriae transcriptome consists of 471 operons which are
      further divided into 167 sub-operon structures. In a differential expression
      analysis approach, we discovered that genetic disruption of the iron-sensing
      transcription regulator DtxR, which controls expression of diphtheria toxin (DT),
      causes a strong influence on general gene expression. Nearly 15% of the genome is
      differentially transcribed, indicating that DtxR might have other regulatory
      functions in addition to regulation of iron metabolism and DT. Furthermore, our
      findings shed light on the transcriptional landscape of the DT encoding gene tox
      and present evidence for two tox antisense RNAs, which point to a new way of
      transcriptional regulation of toxin production. CONCLUSIONS: This study presents
      extensive insights into the transcriptome of C. diphtheriae and provides a basis
      for future studies regarding gene characterization, transcriptional regulatory
      networks, and regulation of the tox gene in particular.

PMID- 29370759
TI  - Identification of Gossypium hirsutum long non-coding RNAs (lncRNAs) under salt
      stress.
AB  - BACKGROUND: Long non-coding RNAs (lncRNAs) represent a class of riboregulators
      that either directly act in long form or are processed into shorter microRNAs
      (miRNAs) and small interfering RNAs. Long noncoding RNAs (lncRNAs) are
      arbitrarily defined as RNA genes larger than 200 nt in length that have no
      apparent coding potential. lncRNAs have emerged as playing important roles in
      various biological regulatory processes and are expressed in a more tissue
      specific manner than mRNA. Emerging evidence shows that lncRNAs participate in
      stress-responsive regulation. RESULTS: In this study, in order to develop a
      comprehensive catalogue of lncRNAs in upland cotton under salt stress, we
      performed whole-transcriptome strand-specific RNA sequencing for three-leaf stage
      cotton seedlings treated with salt stress (S_NaCl) and controls (S_CK). In total
      we identified 1117 unique lncRNAs in this study and 44 differentially expressed
      RNAs were identified as potential non-coding RNAs. For the differentially
      expressed lncRNAs that were identified as intergenic lncRNAs (lincRNA), we
      analysed the gene ontology enrichment of cis targets and found that cis target
      protein-coding genes were mainly enriched in stress-related categories. Real-time
      quantitative PCR confirmed that all selected lincRNAs responsive to salt stress.
      We found lnc_388 was likely as regulator of Gh_A09G1182. And lnc_883 may
      participate in regulating tolerance to salt stress by modulating the expression
      of Gh_D03G0339 MS_channel. We then predicted the target mimics for miRNA in
      Gossypium. six miRNAs were identified, and the result of RT-qPCR with lncRNA and
      miRNA suggested that lnc_973 and lnc_253 may regulate the expression of ghr
      miR399 and ghr-156e as a target mimic under salt stress. CONCLUSIONS: We
      identified 44 lincRNAs that were differentially expressed under salt stress.
      These lincRNAs may target protein-coding genes via cis-acting regulation. We also
      discovered that specifically-expressed lincRNAs under salt stress may act as
      endogenous target mimics for conserved miRNAs. These findings extend the current
      view on lincRNAs as ubiquitous regulators under stress stress.

PMID- 29370760
TI  - Scuba: scalable kernel-based gene prioritization.
AB  - BACKGROUND: The uncovering of genes linked to human diseases is a pressing
      challenge in molecular biology and precision medicine. This task is often
      hindered by the large number of candidate genes and by the heterogeneity of the
      available information. Computational methods for the prioritization of candidate
      genes can help to cope with these problems. In particular, kernel-based methods
      are a powerful resource for the integration of heterogeneous biological
      knowledge, however, their practical implementation is often precluded by their
      limited scalability. RESULTS: We propose Scuba, a scalable kernel-based method
      for gene prioritization. It implements a novel multiple kernel learning approach,
      based on a semi-supervised perspective and on the optimization of the margin
      distribution. Scuba is optimized to cope with strongly unbalanced settings where
      known disease genes are few and large scale predictions are required.
      Importantly, it is able to efficiently deal both with a large amount of candidate
      genes and with an arbitrary number of data sources. As a direct consequence of
      scalability, Scuba integrates also a new efficient strategy to select optimal
      kernel parameters for each data source. We performed cross-validation experiments
      and simulated a realistic usage setting, showing that Scuba outperforms a wide
      range of state-of-the-art methods. CONCLUSIONS: Scuba achieves state-of-the-art
      performance and has enhanced scalability compared to existing kernel-based
      approaches for genomic data. This method can be useful to prioritize candidate
      genes, particularly when their number is large or when input data is highly
      heterogeneous. The code is freely available at https://github.com/gzampieri/Scuba
      .

PMID- 29370761
TI  - Hepatitis C-related cryoglobulinemic neuropathy: potential role of oxcarbazepine
      for pain control.
AB  - BACKGROUND: Peripheral neuropathy is one most common, limiting and invalidating
      neurological symptom in subjects with hepatitis C virus and mixed
      cryoglobulinemia. Notably, the medical therapy proposed to eradicate HCV, can
      frequently exacerbate the painful neuropathy. Therefore, neuropathy therapies are
      insufficient and inadequate, and comprise immunosuppressive drugs, such as
      steroid or cyclosporine, intravenous immunoglobulin or plasma exchange. These
      have shown variable success in case reports, with a presumably temporary effect,
      but with major side effects. METHODS: We assessed the effects of oxcarbazepine
      treatment in 67 cases of cryoglobulinemia related neuropathy, who did not respond
      to either steroid or Gabapentin, or Pregabalin. Oxcarbazepine was chosen based on
      the promising preliminary results. RESULTS: Patients treated with Oxcarbazepine
      showed a rapid, discrete and persistent relief of polyneuropathic signs, without
      consistent side effects, and with a limited interaction with concomitant drugs.
      CONCLUSIONS: These data favor the use of oxcarbazepine as a useful tool in the
      management of neuropathic pain associated with Hepatitis-C cryoglobulin
      neuropathy.

PMID- 29370762
TI  - Circular stripes were more common in Barrett's esophagus after acetic acid
      staining.
AB  - BACKGROUND: The diagnosis of Barrett's esophagus (BE) is disturbed by numerous
      factors, including correct gastroesophageal junction judgment, the initial
      location of the Z-line and the biopsy result above it. The acetic acid (AA) could
      help to diagnose BE better than high resolution imaging technology or magnifying
      endoscopy, by providing enhanced contrast of different epithelium. We have
      noticed AA could produce multiple white circular lines, forming circular stripes
      (CS), at lower esophagus, which hasn't been reported by others. This study aimed
      to investigate whether the CS is a special marker in BE patients. METHODS: A
      total of 47 BE patients and 63 healthy people were enrolled from March 2016 to
      October 2016, and 2% AA staining had been operated routinely at lower esophagus
      under high resolution gastroscopy. We observed whether there were CS after AA
      staining and the images were compared between the two groups. RESULTS: CS were
      confirmed in 42 patients (89.36%) in the BE group and 5 (7.94) in the control
      group ((chi2 = 72.931, P < 0.001)). The average width of CS was 0.76 +/- 0.25 cm
      in BE group, which was similar to that in the control group (0.88 +/- 0.11 cm).
      Villous or punctate or reticular pattern usually existed above or below the CS.
      CONCLUSIONS: CS could be found at lower esophagus in most BE patients with AA
      staining, and this special feature might be valuable in diagnosing, evaluating
      and following up of BE patients.

PMID- 29370763
TI  - Ubiquitin-related genes are differentially expressed in isogenic lines
      contrasting for pericarp cell size and grain weight in hexaploid wheat.
AB  - BACKGROUND: There is an urgent need to increase global crop production.
      Identifying and combining specific genes controlling distinct biological
      processes holds the potential to enhance crop yields. Transcriptomics is a
      powerful tool to gain insights into the complex gene regulatory networks that
      underlie such traits, but relies on the availability of a high-quality reference
      sequence and accurate gene models. Previously, we identified a grain weight QTL
      on wheat chromosome 5A (5A QTL) which acts during early grain development to
      increase grain length through cell expansion in the pericarp. In this study, we
      performed RNA-sequencing on near isogenic lines (NILs) segregating for the 5A QTL
      and used the latest gene models to identify differentially regulated genes and
      pathways that potentially influence pericarp cell size and grain weight in wheat.
      RESULTS: We sampled grains at 4 and 8 days post anthesis and found that genes
      associated with metabolism, biosynthesis, proteolysis and the defence response
      are upregulated during this stage of grain development in both NILs. We
      identified a specific set of 112 transcripts differentially expressed (DE)
      between 5A NILs at either time point, including eight potential candidates for
      the causal 5A gene and its downstream targets. The 112 DE transcripts had
      functional annotations including non-coding RNA, transposon-associated, cell
      cycle control, ubiquitin-related, heat-shock, transcription and histone-related.
      Many of the genes identified belong to families that have been previously
      associated with seed/grain development in other species. Notably, we identified
      DE transcripts at almost all steps of the pathway associated with ubiquitin
      mediated protein degradation. In the promoters of a subset of DE transcripts we
      identified enrichment of binding sites associated with C2H2, MYB/SANT, YABBY, AT
      HOOK and Trihelix transcription factor families. CONCLUSIONS: In this study, we
      identified DE transcripts with a diverse range of predicted biological functions,
      reflecting the complex nature of the pathways that control early grain
      development. Few of these are the direct orthologues of grain size genes in other
      species and none have been previously characterised in wheat. Further functional
      characterisation of these candidates and how they interact will provide novel
      insights into the control of grain size in cereals.

PMID- 29370764
TI  - Key components of the delirium syndrome and mortality: greater impact of acute
      change and disorganised thinking in a prospective cohort study.
AB  - BACKGROUND: Delirium increases the risk of mortality during an acute hospital
      admission. Full syndromal delirium (FSD) is associated with greatest risk and
      subsyndromal delirium (SSD) is associated with intermediate risk, compared to
      patients with no delirium - suggesting a dose-response relationship. It is not
      clear how individual diagnostic symptoms of delirium influence the association
      with mortality. Our objectives were to measure the prevalence of FSD and SSD, and
      assess the effect that FSD, SSD and individual symptoms of delirium (from the
      Confusion Assessment Method-short version (s-CAM)) have on mortality rates.
      METHODS: Exploratory analysis of a prospective cohort (aged >=70 years) with
      acute (unplanned) medical admission (4/6/2007-4/11/2007). The outcome was
      mortality (data censored 6/10/2011). The principal exposures were FSD and SSD
      compared to no delirium (as measured by the CAM), along with individual delirium
      symptoms on the CAM. Cox regression was used to estimate the impact FSD and SSD
      and individual CAM items had on mortality. RESULTS: The cohort (n = 610) mean age
      was 83 (SD 7); 59% were female. On admission, 11% had FSD and 33% had SSD. Of the
      key diagnostic symptoms for delirium, 17% acute onset, 19% inattention, 17%
      disorganised thinking and 17% altered level of consciousness. Unadjusted analysis
      found FSD had an increased hazard ratio (HR) of 2.31 (95% CI 1.71, 3.12), for SSD
      the HR was 1.26 (1.00, 1.59). Adjusted analysis remained significant for FSD
      (1.55 95% CI 1.10, 2.18) but nonsignificant for SSD (HR = 0.92 95% CI 0.70,
      1.19). Two CAM items were significantly associated with mortality following
      adjustment: acute onset and disorganised thinking. CONCLUSION: We observed a dose
      response relationship between mortality and delirium, FSD had the greatest risk
      and SSD having intermediate risk. The CAM items "acute-onset" and "disorganised
      thinking" drove the associations observed. Clinically, this highlights the
      necessity of identifying individual symptoms of delirium.

PMID- 29370765
TI  - Place of death for people with HIV: a population-level comparison of eleven
      countries across three continents using death certificate data.
AB  - BACKGROUND: With over 1 million HIV-related deaths annually, quality end-of-life
      care remains a priority. Given strong public preference for home death, place of
      death is an important consideration for quality care. This 11 country study aimed
      to i) describe the number, proportion of all deaths, and demographics of HIV
      related deaths; ii) identify place of death; iii) compare place of death to
      cancer patients iv), determine patient/health system factors associated with
      place of HIV-related death. METHODS: In this retrospective analysis of death
      certification, data were extracted for the full population (ICD-10 codes B20-B24)
      for 1-year period: deceased's demographic characteristics, place of death,
      healthcare supply. RESULTS: i) 19,739 deaths were attributed to HIV. The highest
      proportion (per 1000 deaths) was for Mexico (9.80/00), and the lowest Sweden
      (0.20/00). The majority of deaths were among men (75%), and those aged <50
      (69.1%). ii) Hospital was most common place of death in all countries: from 56.6%
      in the Netherlands to 90.9% in South Korea. The least common places were hospice
      facility (3.3%-5.7%), nursing home (0%-17.6%) and home (5.9%-26.3%).iii) Age
      standardised relative risks found those with HIV less likely to die at home and
      more likely to die in hospital compared with cancer patients, and in most
      countries more likely to die in a nursing home. iv) Multivariate analysis found
      that men were more likely to die at home in UK, Canada, USA and Mexico; a greater
      number of hospital beds reduced the likelihood of dying at home in Italy and
      Mexico; a higher number of GPs was associated with home death in Italy and
      Mexico. CONCLUSIONS: With increasing comorbidity among people ageing with HIV, it
      is essential that end-of-life preferences are established and met. Differences in
      place of death according to country and diagnosis demonstrate the importance of
      ensuring a "good death" for people with HIV, alongside efforts to optimise
      treatment.

PMID- 29370766
TI  - Description of an advance care planning intervention in nursing homes: outcomes
      of the process evaluation.
AB  - BACKGROUND: Advance Care Planning (ACP) is the repeated communication and
      decision-making process between the patient, family, and healthcare
      professionals. This study describes an ACP intervention in nursing homes and
      evaluates the outcomes of the implementation process. METHODS: The ACP
      intervention was part of a 4-month complex, cluster randomized controlled trial
      (COSMOS). 37 Norwegian nursing homes with 72 units (1 cluster = 1 unit) and 765
      patients were invited to participate and eligible units were randomised to the
      intervention group or control. Nursing home staff in the intervention group was
      offered a standardized education programme to learn early and repeated
      communication with patients and families and to implement ACP in their units. We
      used a train-the-trainer approach to educate staff in the units, supported by
      regular telephone calls and a midway seminar after two months. Individual patient
      logs consisting of different communication deliverables were used to evaluate the
      implementation process. Supported by Qualitative Content Analyses, we identified
      facilitators and barriers of the ACP implementation based on feedback during
      midway seminars and individual patient logs. RESULTS: The ACP intervention was
      conducted in 36 NH units (n = 297); 105 healthcare providers participated at the
      education seminar prior to the study, and 3-4 employees from each unit
      participated in the midway seminar. NH staff reported the educational material
      relevant for the implementation strategy. The patient logs showed that ACP was
      successfully implemented in 62% (n = 183) of the patients using our predefined
      implementation criteria. The staff emphasized the clear communication of the
      relevance of ACP addressed to leaders and staff as important facilitators, along
      with the clearly defined routines, roles and responsibilities. Identified
      barriers included lack of competence, perceived lack of time, and conflicting
      culture and staff opinions. CONCLUSION: Monthly communication with the family was
      the most frequently conducted communication, and the predefined criteria of
      successfully implemented ACP were largely achieved. Nursing home routines and
      engagement of leaders and staff were crucial facilitators, whereas lack of time
      and competence reduced the implementation success. TRIAL REGISTRATION: The COSMOS
      trial was registered in the ClinicalTrials.gov ( NCT02238652 ) July 7th, 2014.

PMID- 29370767
TI  - Medical and moral considerations regarding complex medical decisions in older
      patients with multimorbidity: a compact deliberation framework.
AB  - In health care for older adults, patients with multimorbidity usually receive the
      same interventions as those patients without multimorbidity. However, standard
      curative or life-sustaining treatment options have to be considered carefully in
      view of the maximally attainable result in older and frail patients. To guide
      such complex medical decisions, we present a compact deliberation framework that
      could assist physician(s) in charge of the medical treatment of a specific
      elderly patient to systematize his own thinking about treatment and decisional
      responsibilities, in case of an intercurrent disease.The framework includes four
      questions to be addressed when deciding on a single urgent standard curative or
      life-sustaining intervention in acute medical problems of an elderly patient with
      multimorbidity: 1) What is known about the patient's aims and preferences? 2)
      Will the intervention be effective? 3) Will the intervention support the aims and
      preferences of the patient? 4) In view of the aims and preferences, will the
      risks and benefits be in balance?If all four considerations are answered
      favorably, the intervention will fit patient-centered and appropriate care for
      frail older patients with multimorbidity.Application to a patient case
      illustrates how our framework can improve the quality of the shared decision
      making process in care for older people and helps clarify medical and moral
      considerations regarding how to appropriately treat the individual patient.

PMID- 29370768
TI  - Cost-effectiveness of increasing vaccination in high-risk adults aged 18-64
      Years: a model-based decision analysis.
AB  - BACKGROUND: Adults aged 18-64 years with comorbid conditions are at high risk for
      complications of certain vaccine-preventable diseases, including influenza and
      pneumococcal disease. The 4 PillarsTM Practice Transformation Program (4 Pillars
      Program) increases uptake of pneumococcal polysaccharide vaccine, influenza
      vaccine and tetanus-diphtheria-acellular pertussis vaccine by 5-10% among adults
      with high-risk medical conditions, but its cost-effectiveness is unknown.
      METHODS: A decision tree model estimated the cost-effectiveness of implementing
      the 4 Pillars Program in primary care practices compared to no program for a
      population of adults 18-64 years of age at high risk of illness complications
      over a 10 year time horizon. Vaccination rates and intervention costs were
      derived from a randomized controlled cluster trial in diverse practices in 2 U.S.
      cities. One-way and probabilistic sensitivity analyses were conducted. RESULTS:
      From a third-party payer perspective, which considers direct medical costs, the 4
      Pillars Program cost $28,301 per quality-adjusted life year gained; from a
      societal perspective, which adds direct nonmedical and indirect costs, the
      program was cost saving and more effective than no intervention. Cost
      effectiveness results favoring the program were robust in sensitivity analyses.
      From a public health standpoint, the model predicted that the intervention
      reduced influenza cases by 1.4%, with smaller decreases in pertussis and
      pneumococcal disease cases. CONCLUSION: The 4 Pillars Practice Transformation
      Program is an economically reasonable, and perhaps cost saving, strategy for
      protecting the health of adults aged < 65 years with high-risk medical
      conditions.

PMID- 29370769
TI  - Informal carers' perspectives on the delivery of acute hospital care for patients
      with dementia: a systematic review.
AB  - BACKGROUND: Providing high quality acute hospital care for patients with dementia
      is an increasing challenge as the prevalence of the disease rises. Informal
      carers of people with dementia are a critical resource for improving inpatient
      care, due to their insights into patients' needs and preferences. We summarise
      informal carers' perspectives of acute hospital care to inform best practice
      service delivery. METHODS: We conducted a systematic search of bibliographic
      databases and sought relevant grey literature. We used thematic synthesis
      analysis to assimilate results of the studies and describe components of care
      that influence perceived quality. RESULTS: Twenty papers met the inclusion
      criteria. Findings identified four overarching components of care that influenced
      carer experience and their perceptions of care quality: 'Patient care', 'Staff
      interactions', 'Carer's situation' and 'Hospital environment'. Need for
      improvement was identified in staff training, provision of help with personal
      care needs, and dignified treatment of patients. Carers need to be informed,
      involved and supported during hospital admission in order to promote the most
      positive experience. CONCLUSION: This review identifies common perspectives of
      informal carers of people with dementia in the acute hospital setting and
      highlights important areas to address to improve the experience of an admission
      for both carer and patient.

PMID- 29370770
TI  - Defeat and entrapment: more than meets the eye? Applying network analysis to
      estimate dimensions of highly correlated constructs.
AB  - BACKGROUND: Defeat and entrapment have been shown to be of central relevance to
      the development of different disorders. However, it remains unclear whether they
      represent two distinct constructs or one overall latent variable. One reason for
      the unclarity is that traditional factor analytic techniques have trouble
      estimating the right number of clusters in highly correlated data. In this study,
      we applied a novel approach based on network analysis that can deal with
      correlated data to establish whether defeat and entrapment are best thought of as
      one or multiple constructs. METHODS: Explanatory graph analysis was used to
      estimate the number of dimensions within the 32 items that make up the defeat and
      entrapment scales in two samples: an online community sample of 480 participants,
      and a clinical sample of 147 inpatients admitted to a psychiatric hospital after
      a suicidal attempt or severe suicidal crisis. Confirmatory Factor analysis (CFA)
      was used to test whether the proposed structure fits the data. RESULTS: In both
      samples, bootstrapped exploratory graph analysis suggested that the defeat and
      entrapment items belonged to different dimensions. Within the entrapment items,
      two separate dimensions were detected, labelled internal and external entrapment.
      Defeat appeared to be multifaceted only in the online sample. When comparing the
      CFA outcomes of the one, two, three and four factor models, the one factor model
      was preferred. CONCLUSIONS: Defeat and entrapment can be viewed as distinct, yet,
      highly associated constructs. Thus, although replication is needed, results are
      in line with theories differentiating between these two constructs.

PMID- 29370771
TI  - Characterization of Staphylococcus aureus isolated from patients with burns in a
      regional burn center, Southeastern China.
AB  - BACKGROUND: S.aureus is a predominant pathogen that causes infection in
      critically ill patients, but little information exists regarding the
      characterization of S. aureus from different sources in burn patients in
      southeastern China. METHODS: We enrolled 125 patients with S. aureus infection in
      burns center between Jan 2014 and Dec 2015. S. aureus isolates were characterized
      by antimicrobial susceptibility test, toxin gene detection, and molecular typing
      with multilocus sequence type, staphylococcal protein A (spa) type, and
      staphylococcal cassette chromosome mec (SCCmec) type. RESULTS: Sixty-eight MRSA
      were isolated from SSTI and 31 from non-SSTI patients, respectively. Overall, the
      drug-resistant ability of S. aureus isolated from SSTI was higher than that from
      non-SSTI groups. SCCmecIII-CC239-t030 was the most common clone (38 from SSTIs,
      and 8 from non-SSTIs). Seg was the most common enterotoxin gene (21 from SSTIs
      and 33 from non-SSTIs). Isolates from SSTIs was more likely to carry seb (P =
      0.04), while those from non-SSTIs tended to carry sea and seg (P = 0.002 and
      0.01, respectively). Although isolates carried four hemolysin genes, there was no
      significant difference between them (P > 0.05). CONCLUSION: SCCmecIII-CC239-t030
      was the most common clone in Jiangxi burns center, China. The molecular
      characterization of S. aureus was quite different between SSTI and non-SSTI
      groups.

PMID- 29370772
TI  - Genome-wide characterization of genetic variants and putative regions under
      selection in meat and egg-type chicken lines.
AB  - BACKGROUND: Meat and egg-type chickens have been selected for several generations
      for different traits. Artificial and natural selection for different phenotypes
      can change frequency of genetic variants, leaving particular genomic footprints
      throghtout the genome. Thus, the aims of this study were to sequence 28 chickens
      from two Brazilian lines (meat and white egg-type) and use this information to
      characterize genome-wide genetic variations, identify putative regions under
      selection using Fst method, and find putative pathways under selection. RESULTS:
      A total of 13.93 million SNPs and 1.36 million INDELs were identified, with more
      variants detected from the broiler (meat-type) line. Although most were located
      in non-coding regions, we identified 7255 intolerant non-synonymous SNPs, 512
      stopgain/loss SNPs, 1381 frameshift and 1094 non-frameshift INDELs that may alter
      protein functions. Genes harboring intolerant non-synonymous SNPs affected
      metabolic pathways related mainly to reproduction and endocrine systems in the
      white-egg layer line, and lipid metabolism and metabolic diseases in the broiler
      line. Fst analysis in sliding windows, using SNPs and INDELs separately,
      identified over 300 putative regions of selection overlapping with more than 250
      genes. For the first time in chicken, INDEL variants were considered for
      selection signature analysis, showing high level of correlation in results
      between SNP and INDEL data. The putative regions of selection signatures revealed
      interesting candidate genes and pathways related to important phenotypic traits
      in chicken, such as lipid metabolism, growth, reproduction, and cardiac
      development. CONCLUSIONS: In this study, Fst method was applied to identify high
      confidence putative regions under selection, providing novel insights into
      selection footprints that can help elucidate the functional mechanisms underlying
      different phenotypic traits relevant to meat and egg-type chicken lines. In
      addition, we generated a large catalog of line-specific and common genetic
      variants from a Brazilian broiler and a white egg layer line that can be used for
      genomic studies involving association analysis with phenotypes of economic
      interest to the poultry industry.

PMID- 29370773
TI  - Experiences with and expectations of maternity waiting homes in Luapula Province,
      Zambia: a mixed-methods, cross-sectional study with women, community groups and
      stakeholders.
AB  - BACKGROUND: Luapula Province has the highest maternal mortality and one of the
      lowest facility-based births in Zambia. The distance to facilities limits
      facility-based births for women in rural areas. In 2013, the government
      incorporated maternity homes into the health system at the community level to
      increase facility-based births and reduce maternal mortality. To examine the
      experiences with maternity homes, formative research was undertaken in four
      districts of Luapula Province to assess women's and community's needs, use
      patterns, collaboration between maternity homes, facilities and communities, and
      promising practices and models in Central and Lusaka Provinces. METHODS: A cross
      sectional, mixed-methods design was used. In Luapula Province, qualitative data
      were collected through 21 focus group discussions with 210 pregnant women,
      mothers, elderly women, and Safe Motherhood Action Groups (SMAGs) and 79
      interviews with health workers, traditional leaders, couples and partner agency
      staff. Health facility assessment tools, service abstraction forms and registers
      from 17 facilities supplied quantitative data. Additional qualitative data were
      collected from 26 SMAGs and 10 health workers in Central and Lusaka Provinces to
      contextualise findings. Qualitative transcripts were analysed thematically using
      Atlas-ti. Quantitative data were analysed descriptively using Stata. RESULTS:
      Women who used maternity homes recognized the advantages of facility-based
      births. However, women and community groups requested better infrastructure,
      services, food, security, privacy, and transportation. SMAGs led the construction
      of maternity homes and advocated the benefits to women and communities in
      collaboration with health workers, but management responsibilities of the homes
      remained unassigned to SMAGs or staff. Community norms often influenced women's
      decisions to use maternity homes. Successful maternity homes in Central Province
      also relied on SMAGs for financial support, but the sustainability of these
      models was not certain. CONCLUSIONS: Women and communities in the selected
      facilities accept and value maternity homes. However, interventions are needed to
      address women's needs for better infrastructure, services, food, security,
      privacy and transportation. Strengthening relationships between the managers of
      the homes and their communities can serve as the foundation to meet the needs and
      expectations of pregnant women. Particular attention should be paid to ensuring
      that maternity homes meet quality standards and remain sustainable.

PMID- 29370774
TI  - A complex scenario of tuberculosis transmission is revealed through genetic and
      epidemiological surveys in Porto.
AB  - BACKGROUND: Tuberculosis (TB) incidence is decreasing worldwide and eradication
      is becoming plausible. In low-incidence countries, intervention on migrant
      populations is considered one of the most important strategies for elimination.
      However, such measures are inappropriate in European areas where TB is largely
      endemic, such as Porto in Portugal. We aim to understand transmission chains in
      Porto through a genetic characterization of Mycobacterium tuberculosis strains
      and through a detailed epidemiological evaluation of cases. METHODS: We genotyped
      the M. tuberculosis strains using the MIRU-VNTR system. We performed an
      evolutionary reconstruction of the genotypes with median networks, used in this
      context for the first time. TB cases from a period of two years were evaluated
      combining genetic, epidemiological and georeferencing information. RESULTS: The
      data reveal a unique complex scenario in Porto where the autochthonous population
      acts as a genetic reservoir of M. tuberculosis diversity with discreet episodes
      of transmission, mostly undetected using classical epidemiology alone.
      CONCLUSIONS: Although control policies have been successful in decreasing
      incidence in Porto, the discerned complexity suggests that, for elimination to be
      a realistic goal, strategies need to be adjusted and coupled with a continuous
      genetic characterization of strains and detailed epidemiological evaluation, in
      order to successfully identify and interrupt transmission chains.

PMID- 29370775
TI  - Case report: mechanisms of HIV elite control in two African women.
AB  - BACKGROUND: The majority of people living with HIV require antiretroviral therapy
      (ART) for controlling viral replication, however there are rare HIV controllers
      who spontaneously and durably control HIV in the absence of treatment.
      Understanding what mediates viral control in these individuals has provided us
      with insights into the immune mechanisms that may be important to induce for a
      vaccine or functional cure for HIV. To date, few African elite controllers from
      high incidence settings have been described. We identified virological
      controllers from the CAPRISA 002 cohort of HIV-1 subtype C infected women in
      KwaZulu Natal, South Africa, two (1%) of whom were elite controllers. We examined
      the genetic, clinical, immunological and virological characteristics of these two
      elite HIV controllers in detail, to determine whether they exhibit features of
      putative viral control similar to those described for elite controllers reported
      in the literature. CASE PRESENTATION: In this case report, we present clinical
      features, CD4+ T cell and viral load trajectories for two African women over 7
      years of HIV infection. Viral load became undetectable 10 months after HIV
      infection in Elite Controller 1 (EC1), and after 6 weeks in Elite Controller 2
      (EC2), and remained undetectable for the duration of follow-up, in the absence of
      ART. Both elite controllers expressed multiple HLA Class I and II haplotypes
      previously associated with slower disease progression (HLA-A*74:01, HLA-B*44:03,
      HLA-B*81:01, HLA-B*57:03, HLA-DRB1*13). Fitness assays revealed that both women
      were infected with replication competent viruses, and both expressed higher mRNA
      levels of p21, a host restriction factor associated with viral control. HIV
      specific T cell responses were examined using flow cytometry. EC1 mounted high
      frequency HIV-specific CD8+ T cell responses, including a B*81:01-restricted Gag
      TL9 response. Unusually, EC2 had evidence of pre-infection HIV-specific CD4+ T
      cell responses. CONCLUSION: We identified some features typical of elite
      controllers, including high magnitude HIV-specific responses and beneficial HLA.
      In addition, we made the atypical finding of pre-infection HIV-specific immunity
      in one elite controller, that may have contributed to very early viral control.
      This report highlights the importance of studying HIV controllers in high
      incidence settings.

PMID- 29370776
TI  - The Alu-insertion progesterone receptor gene polymorphism is not associated with
      breast cancer: a meta-analysis.
AB  - BACKGROUND: The role of progesterone receptor (PGR) gene polymorphisms in breast
      cancer is still controversial. Here, we performed a meta-analysis to determine
      whether the Alu insertion is associated with an increased risk of breast cancer
      and, further, whether the Alu insertion contributes to the development of breast
      cancer. METHODS: Using database searches, we selected 10 controlled case studies
      that met a rigorous set of inclusion criteria; these studies included 2106 cases
      and 1660 controls. We generated odds ratios and 95% confidence intervals in order
      to determine the strength of the relationship between the Alu insertion and
      breast cancer incidence. We also performed additional subgroup analyses and
      sensitivity analyses to further clarify the relationship. RESULTS: Using a random
      effects model, we concluded that the Alu insertion was not associated with the
      risk of breast cancer under the dominant genetic model; the pooled OR was 1.025
      (95% CI = 0.526-1.994, p = 0.943). When a subgroup analysis was performed
      according to ethnicity, we found that the Alu insertion was associated with
      breast cancer incidence in Indians and Indo-European mixed racial groups, but the
      association disappeared for patients of Caucasian or Latino decent. CONCLUSIONS:
      Our meta-analysis showed that the Alu-insertion progesterone receptor gene
      polymorphism was not associated with breast cancer. These results provide further
      information regarding the association between the Alu insertion in the PGR gene
      and the incidence of breast cancer.

PMID- 29370777
TI  - Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio can predict the
      severity of gallstone pancreatitis.
AB  - BACKGROUND: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio
      (PLR) predict severity in various diseases. In this study, we evaluated the value
      of NLR and PLR as prognostic factors in acute pancreatitis (AP). METHODS:
      Patients with AP were prospectively enrolled from March 2014 to September 2016 at
      Yonsei University Wonju College of Medicine. NLR and PLR were obtained at
      admission and were compared with other known prognostic scoring systems. RESULTS:
      A total of 243 patients were enrolled with an etiology of gallstone (n = 134) or
      alcohol (n = 109). NLR (17.7 +/- 18.3 vs. 8.8 +/- 8.4, P <  0.001) and PLR (344.1
      +/- 282.6 vs. 177.8 +/- 150.1, P <  0.001) were significantly higher in the
      gallstone AP group than in the alcoholic AP group. For gallstone AP, NLR and PLR
      were significantly higher in severe AP, whereas high NLR and PLR were not related
      to severe AP in alcoholic AP. For the gallstone AP group, NLR and PLR
      demonstrated a predictive value significantly superior to C-reactive protein
      (CRP), whereas NLR, PLR, and CRP were not significant predictors for alcoholic
      AP. CONCLUSION: Our study demonstrated that NLR and PLR can predict the severity
      of AP, but only in gallstone AP.

PMID- 29370778
TI  - Association between socioeconomic status and post-stroke functional outcome in
      deprived rural southern China: a population-based study.
AB  - BACKGROUND: Data on the association between socioeconomic status and post-stroke
      functional outcome in developing countries is lacking. We aimed to evaluate the
      association in stroke survivors in deprived rural Southern China. METHODS: We
      conducted door-to-door interviews and collected data using a structured
      questionnaire in stroke survivors from five fourth-class rural areas of Guangdong
      Province through a non-government initiated registry from August 2014 to March
      2015. Descriptive statistics were used to provide information on the demographic,
      socioeconomic and clinical characteristics of the selected population. Univariate
      and multivariate logistic regression were used to examine the relationship of
      socioeconomic status indexed by self-reported average family income and
      functional impairment defined as a modified Rankin Scale of 3 to 5. RESULTS:
      Among the 425 stroke survivors, 52.7% lived below the poverty line set by the
      local government. About 50% of patients suffered from functional impairment and
      required assistance in their daily life. Compared with their wealthier
      counterpart, stroke survivors with lower income were more likely to have
      functional impairment (OR 2.85, 95% CI 1.93-4.23). The effect size increased and
      remained significant after adjusting for possible confounding factors (OR 3.17,
      95% CI 2.04-4.91). CONCLUSIONS: Poorer patients tend to have poorer post-stroke
      functional outcome. Primary and secondary strategies targeting underprivileged
      populations in less-developed areas are thus urgently needed in China.

PMID- 29370779
TI  - HIV/AIDS workplace policy addressing epidemic drivers through workplace programs.
AB  - BACKGROUND: HIV workplace policies have become an important tool in addressing
      the HIV Pandemic in Sub-Saharan Africa. In Zambia, the National AIDS Council has
      been advocating for establishing of HIV/AIDS workplace policies to interested
      companies, however no formal evaluation has been done to assess uptake and
      implementation. The study aimed to establish the existence of HIV/AIDS policies
      and programs in the private sector and to understand implementation factors and
      experiences in addressing HIV epidemic drivers through these programs. METHODS: A
      mixed method assessment of the availability of policies was conducted in 128
      randomly selected member companies of Zambia Federation of Employers in Lusaka.
      Categorized variables were analysed on Policy and programs using Stata version
      12.0 for associations: Concurrently, 28 in-depth interviews were conducted on
      purposively sampled implementers. Qualitative results were analysed thematically
      before integrating them with qualitative findings. RESULTS: Policies were found
      in 47/128 (36.72%) workplaces and the private sector accounted for 34/47 (72.34%)
      of all workplaces with a policy. Programs were available in 56/128 (43.75%)
      workplaces. The availability of policy was 2.7 times more likely to occur with
      increased size of a workplace, P value = 0.0001, (P < 0.05). Management support
      was 0.253 times more likely to occur in workplaces with policy, P value = 0.013,
      (P < 0.05) compared to those without. Having a specific budget for programs was
      0.23 times more likely to occur in workplaces with a policy (P < 0.05) than those
      without a policy. Implementation was hindered by reduced funding, lack of time,
      sensitisation and lack of monitoring/evaluation systems. HIV awareness (56/56,
      100%) and HIV/AIDS/Stigma (47/56, 83.93%) were the most addressed epidemic
      drivers through programs while Mother to Child Transmission (30/56 53.57%) and
      Males having sex with males were the least addressed (18/56, 32.14%). CONCLUSION:
      HIV/AIDS policies exist in the private sector at a very low proportion but policy
      translation was very high suggesting that workplaces with polices are likely to
      implement programs. The eradication of HIV/AIDS by 2030, requires addressing
      epidemic drivers with a focus on marginalised populations, gender integration, a
      wellness and rights based approach within the context of the legal framework.

PMID- 29370780
TI  - Prevalence and intensity of Ascaris lumbricoides infections in relation to
      undernutrition among children in a tea plantation community, Sri Lanka: a cross
      sectional study.
AB  - BACKGROUND: Ascaris lumbricoides infections are one of the commonnest intestinal
      nematode infections in the world, with a profound negative effect on nutritional
      status among underprivileged populations. In Sri Lanka, Ascaris infections and
      low nutritional status still persist in the plantation sector. However, research
      regarding the association between Ascaris infections and nutritional status is
      scarce. The main purpose of this study was to determine the association between
      Ascaris infections and physical growth among children in a plantation sector in
      Sri Lanka. METHODS: A cross sectional study was conducted among 489 children aged
      between 1 and 12 years ina plantation sector, Sri Lanka, from January to April
      2013. Anthropometric measurements were collected to assess height-for-age (HAZ),
      weight-for-age (WAZ) and weight-for-height (WHZ) to determine stunting,
      underweight and wasting respectively. Data on socio-demographic and
      antihelminthic treatment were ascertained using an interviewer administrated
      structured questionnaire. Stool samples were subjected to wet mount preparation
      followed byformaldehyde-ether sedimentation technique to diagnose Ascaris
      infection and a Kato Katz technique was performed to determine the eggs
      intensity. AnthroPlus, EpiInfo and SPSS software was used to analyze data.
      RESULTS: Of the study sample, 38.4% showed Ascaris lumbricoides infections. Light
      intensity infections (51%) were common in the infected children, followed by
      moderate (30%) and heavy (19%) infections. Prevalence of Ascaris infections was
      significantly associated with de-worming more than six months prior to the study.
      Prevalence of undernutrition among children was 61.7%. Forty-five per cent were
      underweight, while 24.1% and 21.5% of children were stunted and wasted
      respectively. However, no significant association was found between Ascaris
      infections status and undernutrition. Meanwhile, heavy intensity infections were
      associated with decreased values of WHZ (p = 0.020). CONCLUSIONS: Ascaris
      infections and undernutrition are still highly prevalent and a major public
      health problem in the plantation sector in Sri Lanka. Health and nutrition
      intervention programs should be implemented to increase the nutritional status of
      children.

PMID- 29370781
TI  - The PANDA study: a randomized phase II study of first-line FOLFOX plus
      panitumumab versus 5FU plus panitumumab in RAS and BRAF wild-type elderly
      metastatic colorectal cancer patients.
AB  - BACKGROUND: Few data are available regarding the treatment of metastatic
      colorectal cancer elderly patients with anti-EGFR agents in combination with
      chemotherapy. FOLFOX plus panitumumab is a standard first-line option for RAS
      wild-type metastatic colorectal cancer. Slight adjustments in chemo-dosage are
      commonly applied in clinical practice to elderly patients, but those modified
      schedules have never been prospectively tested. Clinical definition of elderly
      (>=70 years old) patients that may deserve a more or less intensive combination
      therapy is still debated. Several geriatric screening tools have been developed
      to predict survival and risk of toxicity from treatment. Among those, the G8
      screening tool has been tested in cancer patients showing the strongest
      prognostic value for overall survival, while the CRASH score can stratify
      patients according to an estimated risk of treatment-related toxicities. METHODS:
      The PANDA study is a prospective, open-label, multicenter, randomized phase II
      trial of first-line therapy with panitumumab in combination with dose-adjusted
      FOLFOX or with 5-fluorouracil monotherapy, in previously untreated elderly
      patients (>=70 years) with RAS and BRAF wild-type unresectable metastatic
      colorectal cancer. RAS and BRAF analyses are centralized. Geriatric assessment by
      means of G8 and CRASH score is planned at baseline and G8 will be re-evaluated at
      disease progression. The primary endpoint is duration of progression-free
      survival in both arms. Secondary endpoints include prospective evaluation of the
      prognostic role of G8 score and the correlation of CRASH risk categories with
      toxicity. DISCUSSION: The PANDA study aims at exploring safety and efficacy of
      panitumumab in combination with FOLFOX or with 5FU/LV in elderly patients
      affected by RAS and BRAF wild-type metastatic colorectal cancer, to identify the
      most promising treatment strategy in this setting. Additionally, this is the
      first trial in which the prognostic role of the G8 score will be prospectively
      evaluated. Results of this study will drive further experimental developments for
      one or both combinations. TRIAL REGISTRATION: PANDA is registered at
      Clinicaltrials.gov : NCT02904031 , July 11, 2016. PANDA is registered at EudraCT
      No.: 2015-003888-10, September 3, 2015.

PMID- 29370783
TI  - Breast cancer risk in a screening cohort of Asian and white British/Irish women
      from Manchester UK.
AB  - BACKGROUND: The differences between breast cancer risk factors in white
      British/Irish and Asian women attending screening in the UK are not well
      documented. METHODS: Between 2009-15 ethnicity and traditional breast cancer risk
      factors were self-identified by a screening cohort from Greater Manchester, with
      follow up to 2016. Risk factors and incidence rates were compared using age
      standardised statistics (European standard population). RESULTS: Eight hundred
      and seventy-nine Asian women and 51,779 unaffected white British/Irish women aged
      46-73 years were recruited. Asian women were at lower predicted breast cancer
      risk from hormonal and reproductive risk factors than white British/Irish women
      (mean 10 year risk 2.6% vs 3.1%, difference 0.4%, 95%CI 0.3-0.5%). White
      British/Irish women were more likely to have had a younger age at menarche, be
      overweight or obese, taller, used hormone replacement therapy and not to have had
      children.. However, despite being less overweight Asian women had gained more
      weight from age 20 years and were less likely to undertake moderate physical
      activity. Asian women also had a slightly higher mammographic density. Asian age
      standardised incidence was 3.2 (95%CI 1.6-5.2, 18 cancers) per thousand
      women/year vs 4.5 (95%CI 4.2-4.8, 1076 cancers) for white British/Irish women.
      CONCLUSIONS: Asian women attending screening in Greater Manchester are likely to
      have a lower risk of breast cancer than white British/Irish women, but they
      undertake less physical activity and have more adult weight gain.

PMID- 29370782
TI  - Leptin-induced ER-alpha-positive breast cancer cell viability and migration is
      mediated by suppressing CCN5-signaling via activating JAK/AKT/STAT-pathway.
AB  - BACKGROUND: In menopausal women, one of the critical risk factors for breast
      cancer is obesity/adiposity. It is evident from various studies that leptin, a 16
      kDa protein hormone overproduced in obese people, plays the critical role in
      neovascularization and tumorigenesis in breast and other organs. However, the
      mechanisms by which obesity influences the breast carcinogenesis remained
      unclear. In this study, by analyzing different estrogen receptor-alpha (ER-alpha)
      positive and ER-alpha-negative BC cell lines, we defined the role of CCN5 in the
      leptin-mediated regulation of growth and invasive capacity. METHODS: We analyzed
      the effect of leptin on cell viability of ER-alpha-positive MCF-7 and ZR-75-1
      cell lines and ER-alpha-negative MDA-MB-231 cell line. Additionally, we also
      determined the effect of leptin on the epithelial-mesenchymal transition (EMT)
      bio-markers, in vitro invasion and sphere-formation of MCF-7 and ZR-75-1 cell
      lines. To understand the mechanism, we determined the impact of leptin on CCN5
      expression and the functional role of CCN5 in these cells by the treatment of
      human recombinant CCN5 protein(hrCCN5). Moreover, we also determined the role of
      JAK-STAT and AKT in the regulation of leptin-induced suppression of CCN5 in BC
      cells. RESULTS: Present studies demonstrate that leptin can induce cell
      viability, EMT, sphere-forming ability and migration of MCF-7 and ZR-75-1 cell
      lines. Furthermore, these studies found that leptin suppresses the expression of
      CCN5 at the transcriptional level. Although the CCN5 suppression has no impact on
      the constitutive proliferation of MCF-7 and ZR-75-1 cells, it is critical for
      leptin-induced viability and necessary for EMT, induction of in vitro migration
      and sphere formation, as the hrCCN5 treatment significantly inhibits the leptin
      induced viability, EMT, migration and sphere-forming ability of these cells.
      Mechanistically, CCN5-suppression by leptin is mediated via activating
      JAK/AKT/STAT-signaling pathways. CONCLUSIONS: These studies suggest that CCN5
      serves as a gatekeeper for leptin-dependent growth and progression of luminal
      type (ER-positive) BC cells. Leptin may thus need to destroy the CCN5-barrier to
      promote BC growth and progression via activating JAK/AKT/STAT signaling.
      Therefore, these observations suggest a therapeutic potency of CCN5 by
      restoration or treatment in obese-related luminal-type BC growth and progression.

PMID- 29370784
TI  - Students' perception of interprofessional education in the bachelor programme
      "Interprofessional Health Care" in Heidelberg, Germany: an exploratory case
      study.
AB  - BACKGROUND: Interprofessional education is receiving increased attention
      worldwide. This has led to the development of a bachelor programme
      "Interprofessional Health Care" at the University of Heidelberg, Germany
      beginning in the winter semester 2011. Aim of this study was to evaluate the
      students' perception of this innovative programme regarding interprofessional
      learning. METHODS: An exploratory case study was conducted. A semi-structured
      guideline was developed and seven focus groups were performed with the students
      of the first three cohorts in 2012-2014. Data was transcribed and analyzed using
      content analysis leading to main categories, one of which was titled
      "interprofessional learning". This article presents the results focussing on the
      students' experiences regarding interprofessional education and learning during
      their first two semesters of the programme. RESULTS: Four main categories related
      to interprofessional learning were developed inductively. Students assessed
      "interprofessional learning" in general as positive and wished to encounter a
      more intense experience and collaboration with different health professions
      during their studies. Students reported to benefit from the programme due to a
      better understanding of other professions and their different perspectives. They
      described decreased hesitance to approach other health professions in every day
      practice. Results are in line with the four domains of the Interprofessional Core
      Competencies. CONCLUSION: All in all students at an early stage recognized the
      benefit of interprofessional learning for their studies and their everyday work
      in practice showing the way forward for the bachelor programme and encouraging
      more interprofessional encounters with students from other health care
      programmes.

PMID- 29370785
TI  - Potential loss of revenue due to errors in clinical coding during the
      implementation of the Malaysia diagnosis related group (MY-DRG(r)) Casemix system
      in a teaching hospital in Malaysia.
AB  - BACKGROUND: The accuracy of clinical coding is crucial in the assignment of
      Diagnosis Related Groups (DRGs) codes, especially if the hospital is using
      Casemix System as a tool for resource allocations and efficiency monitoring. The
      aim of this study was to estimate the potential loss of income due to an error in
      clinical coding during the implementation of the Malaysia Diagnosis Related Group
      (MY-DRG(r)) Casemix System in a teaching hospital in Malaysia. METHODS: Four
      hundred and sixty-four (464) coded medical records were selected, re-examined and
      re-coded by an independent senior coder (ISC). This ISC re-examined and re-coded
      the error code that was originally entered by the hospital coders. The pre- and
      post-coding results were compared, and if there was any disagreement, the codes
      by the ISC were considered the accurate codes. The cases were then re-grouped
      using a MY-DRG(r) grouper to assess and compare the changes in the DRG assignment
      and the hospital tariff assignment. The outcomes were then verified by a casemix
      expert. RESULTS: Coding errors were found in 89.4% (415/424) of the selected
      patient medical records. Coding errors in secondary diagnoses were the highest,
      at 81.3% (377/464), followed by secondary procedures at 58.2% (270/464),
      principal procedures of 50.9% (236/464) and primary diagnoses at 49.8% (231/464),
      respectively. The coding errors resulted in the assignment of different MY-DRG(r)
      codes in 74.0% (307/415) of the cases. From this result, 52.1% (160/307) of the
      cases had a lower assigned hospital tariff. In total, the potential loss of
      income due to changes in the assignment of the MY-DRG(r) code was RM654,303.91.
      CONCLUSIONS: The quality of coding is a crucial aspect in implementing casemix
      systems. Intensive re-training and the close monitoring of coder performance in
      the hospital should be performed to prevent the potential loss of hospital
      income.

PMID- 29370786
TI  - Disease progression in idiopathic pulmonary fibrosis with mild physiological
      impairment: analysis from the Australian IPF registry.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal
      fibrosing lung disease of unknown cause. The advent of anti-fibrotic medications
      known to slow disease progression has revolutionised IPF management in recent
      years. However, little is known about the natural history of IPF patients with
      mild physiological impairment. We aimed to assess the natural history of these
      patients using data from the Australian IPF Registry (AIPFR). METHODS: Using our
      cohort of real-world IPF patients, we compared FVC criteria for mild
      physiological impairment (FVC >= 80%) against other proposed criteria: DLco >=
      55%; CPI <=40 and GAP stage 1 with regards agreement in classification and
      relationship with disease outcomes. Within the mild cohort (FVC >= 80%), we also
      explored markers associated with poorer prognosis at 12 months. RESULTS: Of the
      416 AIPFR patients (mean age 70.4 years, 70% male), 216 (52%) were classified as
      'mild' using FVC >= 80%. There was only modest agreement between FVC and DLco (k
      = 0.30), with better agreement with GAP (k = 0.50) and CPI (k = 0.48). Patients
      who were mild had longer survival, regardless of how mild physiologic impairment
      was defined. There was, however, no difference in the annual decline in FVC%
      predicted between mild and moderate-severe groups (for all proposed criteria).
      For patients with mild impairment (n = 216, FVC >= 80%), the strongest predictor
      of outcomes at 12 months was oxygen desaturation on a 6 min walk test.
      CONCLUSION: IPF patients with mild physiological impairment have better survival
      than patients with moderate-severe disease. Their overall rate of disease
      progression however, is comparable, suggesting that they are simply at different
      points in the natural history of IPF disease.

PMID- 29370788
TI  - Comparison of single-dose radial extracorporeal shock wave and local
      corticosteroid injection for treatment of carpal tunnel syndrome including mid
      term efficacy: a prospective randomized controlled trial.
AB  - BACKGROUND: Recent studies have reported that radial extracorporeal shock wave
      therapy (rESWT) reduces pain and improves function in patients with mild to
      moderately severe carpal tunnel syndrome (CTS) compared to a placebo. However,
      most of those studies used multi-session rESWT combined with wrist support and
      evaluation of efficacy was limited to a maximum of 14 weeks. METHODS: The
      prospective randomized controlled trial compared efficacy in relieving pain and
      improving clinical function between single-dose rESWT and local corticosteroid
      injection (LCsI) over the mid-term (24 weeks). Twenty-five patients with mild to
      moderately severe CTS were randomized to receive either single-dose rESWT (n =
      13) or LCsI (n = 12). Primary outcomes were evaluated using the Boston self
      assessment questionnaire (BQ), while secondary outcomes used the Visual analogue
      scale (VAS) and electrodiagnostic parameters. Evaluations at baseline and at 1,
      4, 12 and 24 weeks after treatment were performed. RESULTS: There was
      significantly greater improvement in symptom severity scores, functional scores
      and Boston questionnaire scores at weeks 12 to 24 in the rESWT group compared to
      the LCsI group. When compared to the baseline, there was significant reduction of
      VAS and functional score in the rESWT group at weeks 12 and 24. The LCsI group
      had no statistically significant differences in VAS reduction and functional
      score of the same period. CONCLUSIONS: Treatment of CTS using single-dose rESWT
      has a carry-over effect lasting up to 24 weeks suggesting that single-dose rESWT
      is appropriate for treatment of mild to moderate CTS and provides longer-lasting
      benefits than LCsI. TRIAL REGISTRATION: ( TCTR20150709001 ). Registered 9 July
      2015.

PMID- 29370787
TI  - The association between electrodermal activity (EDA), depression and suicidal
      behaviour: A systematic review and narrative synthesis.
AB  - BACKGROUND: Electrodermal activity (EDA) and other peripheral autonomic
      electrical parameters have been used as indicators of emotional states, including
      depressive states and suicidal state. We aimed to review EDA research
      systematically, focusing on EDA's usefulness as a biomarker for depression and
      suicidal behaviour. METHODS: We searched MEDLINE, Scopus, Cochrane Library, and
      Web of Science databases, following PRISMA guidelines. The initial screening of
      articles was based on titles and abstracts; then the full text was reviewed. A
      preliminary synthesis of findings was developed using tables, thematic analysis
      and quality ratings. RESULTS: 1287 articles were screened and 77 relevant studies
      were identified and included in the systematic review. The studies were fairly
      consistent in maintaining that hypoactive electrodermal response is an
      established feature of patients affected by depression. There is also preliminary
      evidence that monitoring EDA may help to differentiate the phases of mood
      disorders. A few studies provided evidence that EDA can be used to differentiate
      acutely suicidal subjects from depressed patients who are not severely suicidal.
      Although EDA has been shown to be a valid, sensitive marker of suicidal ideation,
      suicide attempts and violent suicidal behaviour, it also seems to be influenced
      to some extent by antidepressant treatment. CONCLUSIONS: Most of the studies
      summarised in this review are quite outdated and employed a variety of designs
      and methods to evaluate EDA. This limits the generalisability of the results and
      makes it difficult to draw clear conclusions about the role of EDA in real-world
      settings. Electrodermal hypoactivity seems to be a reliable feature of depression
      and a valid marker of suicidal risk. Nevertheless, the potential utility of EDA
      in diagnosis, prevention, and treatment planning for depression and suicidal
      behaviour, should be thoroughly studied.

PMID- 29370789
TI  - Patterns and predictors of adherence to colorectal cancer screening
      recommendations in Alberta's Tomorrow Project participants stratified by risk.
AB  - BACKGROUND: Colorectal cancer (CRC) screening is an important modifiable
      behaviour for cancer control. Regular screening, following recommendations for
      the type, timing and frequency based on personal CRC risk, contributes to earlier
      detection and increases likelihood of successful treatment. METHODS: To determine
      adherence to screening recommendations in a large provincial cohort of adults,
      participants in Alberta's Tomorrow Project (n = 9641) were stratified based on
      increasing level of CRC risk: age (Age-only), family history of CRC (FamilyHx),
      personal history of bowel conditions (PersonalHx), or both (Family/PersonalHx)
      using self-reported information from questionnaires. Provincial and national
      guidelines for timing and frequency of screening tests were used to determine if
      participants were up-to-date based on their CRC risk. Screening status was
      compared between enrollment (2000-2006) and follow-up (2008) to determine
      screening pattern over time. RESULTS: The majority of participants (77%) fell
      into the average risk Age-only strata. Only a third of this strata were up-to
      date for screening at baseline, but the proportion increased across the higher
      risk strata, with > 90% of the highest risk Family/PersonalHx strata up-to-date
      at baseline. There was also a lower proportion (< 25%) of the Age-only group who
      were regular screeners over time compared to the higher risk strata, though age,
      higher income and uptake of other screening tests (e.g. mammography) were
      associated with a greater likelihood of regular screening in multinomial logistic
      regression. CONCLUSIONS: The low (< 50%) adherence to regular CRC screening in
      average and moderate risk strata highlights the need to further explore barriers
      to uptake of screening across different risk profiles.

PMID- 29370790
TI  - Oncological and functional results after surgical treatment of bone metastases at
      the proximal femur.
AB  - BACKGROUND: Metastatic lesions to the proximal femur occur frequently (about 10%
      of patients with cancer) and require surgical treatment. There are many surgical
      methods of treatment, however, use of the tumor modular endoprostheses seems to
      be particularly promising. The aim of study was to evaluate oncological and
      functional results of treatment in patients with proximal femur metastases.
      Oncological results were evaluated considering the survival of patients and the
      number of local recurrences. Functional results were assessed as pain intensity
      in VAS score and performance in Karnofsky and MSTS score. METHODS: Between 2010
      and 2016, 122 patients with metastatic tumour to the proximal femur were treated
      in our hospital. Majority of the patients were women - 77 patients. The mean age
      was 67 years for women and 72 years for men. Pathological fracture was diagnosed
      in 98 cases. Metastatic bone tumors commonly develop from breast cancer - 48 and
      myeloma - 24. One hundred one patients underwent tumor resection and in 21 cases
      metastatic tumors was not resected. In 75 patients wide tumour resection and
      modular endoprosthetic replacement were prefomed. Twenty-one patients underwent
      standard or long stem hip endoprosthetic replacement. Intramedullary gamma nails
      were implanted in 20 cases and DHS plate in 6 cases. In 92 cases 3-4 weeks after
      surgery patients undergo external beam radiotherapy (8Gy). Functional results
      were assessed as pain intensity in VAS score and performance in Karnofsky and
      MSTS score. Oncological results were evaluated considering the survival of
      patients and the number of local recurrences. RESULTS: The mean follow-up of
      patients was 27 months (min 4, max 51). Forty-five patients died before last
      visit in hospital. The mean survival after modular endoprosthetic replacement was
      860 days and after bone fixations 360 days. We noticed 9 cases of local
      recurrences or progressions, 6 in patients who had no radiotherapy. Three
      patients after modular endoprosthesis replacement and 6 after bone fixations.
      After surgery, all patients experienced improvement in the comfort of life
      resulting from reduction in pain. Mean VAS score before modular endoprosthetic
      replacement was 6.8 and after 3.4; before standard prothesoplasty 4.9 and after
      2.8; and before and after bone fixation 6.9 -5.1. Mean MSTS score was
      respectively 6.4-19.8; 8.8-22.4 and 10.8-18.2. In 6 patients after modular
      endoprosthesis replacement, delayed wound healing were observed. Infectious
      complications were not observed after fixation with nails and plates. In 3 cases,
      the fixation was failed. The systemic complications affected 12 patients.
      CONCLUSIONS: Results of surgical treatment for metastases to the proximal femur
      are particularly good in patients after standard or modular endoprostheses
      replacement. The author considers this treatment method to be optimal in patients
      with good prognosis.

PMID- 29370791
TI  - The use of external change agents to promote quality improvement and
      organizational change in healthcare organizations: a systematic review.
AB  - BACKGROUND: External change agents can play an essential role in healthcare
      organizational change efforts. This systematic review examines the role that
      external change agents have played within the context of multifaceted
      interventions designed to promote organizational change in healthcare
      specifically, in primary care settings. METHODS: We searched PubMed, CINAHL,
      Cochrane, Web of Science, and Academic Search Premier Databases in July 2016 for
      randomized trials published (in English) between January 1, 2005 and June 30,
      2016 in which external agents were part of multifaceted organizational change
      strategies. The review was conducted according to PRISMA guidelines. A total of
      477 abstracts were identified and screened by 2 authors. Full text articles of
      113 studies were reviewed. Twenty-one of these studies were selected for
      inclusion. RESULTS: Academic detailing (AD) is the most prevalently used
      organizational change strategy employed as part of multi-component implementation
      strategies. Out of 21 studies, nearly all studies integrate some form of audit
      and feedback into their interventions. Eleven studies that included practice
      facilitation into their intervention reported significant effects in one or more
      primary outcomes. CONCLUSIONS: Our results demonstrate that practice facilitation
      with regular, tailored follow up is a powerful component of a successful
      organizational change strategy. Academic detailing alone or combined with audit
      and feedback alone is ineffective without intensive follow up. Provision of
      educational materials and use of audit and feedback are often integral components
      of multifaceted implementation strategies. However, we didn't find examples where
      those relatively limited strategies were effective as standalone interventions.
      System-level support through technology (such as automated reminders or alerts)
      is potentially helpful, but must be carefully tailored to clinic needs.

PMID- 29370792
TI  - What do we know about managing Dupuytren's disease cost-effectively?
AB  - BACKGROUND: Dupuytren's disease (DD) is a common and progressive,
      fibroproliferative disorder of the palmar and digital fascia of the hand. Various
      treatments have been recommended for advanced disease or to retard progression of
      early disease and to prevent deterioration of the finger contracture and quality
      of life. Recent studies have tried to evaluate the clinical and cost
      effectiveness of therapies for DD, but there is currently no systematic
      assessment and appraisal of the economic evaluations. METHODS: A systematic
      literature review was conducted, following PRISMA guidelines, to identify studies
      reporting economic evaluations of interventions for managing DD. Databases
      searched included the Ovid MEDLINE/Embase (without time restriction), National
      Health Service (NHS) Economic Evaluation Database (all years) and the National
      Institute for Health Research (NIHR) Journals Library) Health Technology
      Assessment (HTA). Cost-effectiveness analyses of treating DD were identified and
      their quality was assessed using the CHEERS assessment tool for quality of
      reporting and Phillips checklist for model evaluation. RESULTS: A total of 103
      studies were screened, of which 4 met the study inclusion criteria. Two studies
      were from the US, one from the UK and one from Canada. They all assessed the same
      interventions for advanced DD, namely collagenase Clostridium histolyticum
      injection, percutaneous needle fasciotomy and partial fasciectomy. All studies
      conducting a cost-utility analysis, two implemented a decision analytic model and
      two a Markov model approach. None of them were based on a single randomised
      controlled trial, but rather synthesised evidence from various sources. Studies
      varied in their time horizon, sources of utility estimates and perspective of
      analysis. The overall quality of study reporting was good based on the CHEERS
      checklist. The quality of the model reporting in terms of model structure, data
      synthesis and model consistency varied across the included studies. CONCLUSION:
      Cost-effectiveness analyses for patients with advanced DD are limited and have
      applied different approaches with respect to modelling. Future studies should
      improve the way they are conducted and report their findings according to
      established guidance for conducting economic modelling of health care
      technologies. TRIAL REGISTRATION: The protocol was registered ( CRD42016032989 ;
      date 08/01/2016) with the PROSPERO international prospective register of
      systematic reviews.

PMID- 29370793
TI  - Cross-validation of a learning climate instrument in a non-western postgraduate
      clinical environment.
AB  - BACKGROUND: In postgraduate training, there is a need to continuously assess the
      learning and working conditions to optimize learning. Students or trainees
      respond to the learning climate as they perceive it. The Dutch Residency
      Educational Climate Test (D-RECT) is a learning climate measurement tool with
      well-substantiated validity. However, it was originally designed for Dutch
      postgraduate trainees and it remains to be shown whether extrapolation to non
      Western settings is viable. The dual objective of this study was to revalidate D
      RECT outside of a Western setting and to evaluate the factor structure of a
      recently revised version of the D-RECT containing 35 items. METHODS: We invited
      Filipino internal medicine residents from 96 hospitals to complete the revised 35
      item D-RECT. Subsequently, we performed a confirmatory factor analysis to check
      the fit of the 9 scale model of the revised 35-item D-RECT. Inter-rater
      reliability was assessed using generalizability theory. RESULTS: Confirmatory
      factor analysis unveiled that the factor structure of the revised 35-item D-RECT
      provided a reasonable fit to the Filipino data, after removal of 7 items. Five to
      seven evaluations of individual residents were needed per scale to obtain a
      reliable result. CONCLUSION: Even in a non-Western setting, the D-RECT exhibited
      psychometric validity. This study validated the factor structure of the revised
      35-item D-RECT after some modifications. We recommend that its application be
      extended to other Asian countries and specialties.

PMID- 29370794
TI  - Anti-proliferative and cytotoxic activities of Allium autumnale P. H. Davis
      (Amaryllidaceae) on human breast cancer cell lines MCF-7 and MDA-MB-231.
AB  - BACKGROUND: Natural products obtained from plants can be potent sources for
      developing a variety of pharmaceutical products. Allium species have been widely
      studied for their anti-cancer effects and presented promising results as
      potential anti-cancer agents. Breast cancer (BCa) is one of the most commonly
      diagnosed types of cancer in women. In this study, we aimed to investigate the
      anti-proliferative, cytotoxic and anti-metastatic effects of bulb and stem
      extracts from Allium autumnale P. H. Davis (Amaryllidaceae), an endemic Allium
      species to the island of Cyprus, in a comparative approach to weakly metastatic
      MCF-7 and strongly metastatic MDA-MB-231 breast cancer (BCa) cell lines. METHODS:
      Possible cytotoxic, anti-proliferative and anti-metastatic effects of the Allium
      extracts on MCF-7 and MDA-MB-231 cells were tested using trypan blue exclusion,
      MTT and wound heal assays, respectively. Gas Chromatography Mass Spectroscopy (GC
      MS) analysis was performed to determine the prominent medically important
      compounds in Allium autumnale bulb (AAB) and Allium autumnale stem (AAS)
      extracts. Student unpaired t-test or ANOVA followed by Newman-Keuls post hoc
      analysis (INSTAT Software) was used where appropriate. RESULTS: Our results
      demonstrate that AAB extract (24, 48 and 72 h) exerts significant anti
      proliferative effect on both MCF-7 and MDA-MB-231 cells where this effect for AAS
      extract was observed only at high (5000 and 10,000 MUg/mL) concentrations. Cell
      viability experiments revealed that AAB extract incubations caused more
      cytotoxicity on both BCa cell lines compared to the AAS. In contrast, there was
      no effect on lateral motilities of either cell line. CONCLUSION: Overall, our
      studies demonstrated the anti-cancer activities associated with Allium autumnale,
      revealing it's cytotoxic and anti-proliferative potential to be further utilized
      in in vivo studies.

PMID- 29370795
TI  - Preparing for a trial to test a postpartum weight retention intervention among
      low income women: feasibility of a protocol in a community-based organization.
AB  - BACKGROUND: Postpartum weight retention (PPWR) causes intergenerational harm,
      negatively affecting a mother's cardiovascular health and ability to have future
      healthy pregnancies. Low-income minority women are at highest risk for PPWR with
      little guidance concerning timeline or strategy to lose weight after delivery. An
      academic-community partnership conducted observational and focus group work to
      develop an intervention for PPWR among low-income mothers. This study's objective
      is to determine the feasibility of implementing a PPWR intervention trial in
      partnership with a community-based organization (CBO) serving low-income families
      with social service support. METHODS: We analyzed five implementation outcomes in
      this feasibility study: acceptability, adoption, appropriateness, penetration,
      and sustainability. Other secondary outcomes were the change in psychosocial and
      clinical outcomes from baseline to one year following the intervention delivery.
      RESULTS: An academic-community partnership developed and piloted a postpartum
      weight retention intervention among 17 participants that included 1) six weeks of
      interactive daily health texting, 2) exercise assistance with baby carrier, home
      exercise program, and pedometer provision, 3) two live healthy eating and baby
      feeding workshops, and 4) two 45-min home visits over one year to provide social
      support and acquire followup data. Implementation outcomes demonstrate an
      intervention supported by the organization and accepted by end-users, with
      increased capacity of the CBO to test and deliver an effective intervention.
      Weight loss was achieved by the majority of participants at one year (Md - 5
      pounds (IQR = - 14.5 - 0.3). CONCLUSION: We made protocol enhancements to the
      developed intervention based on the analysis of this study, and now prepare for a
      funded randomized controlled trial (RCT) in a community-based setting. Our
      central hypothesis is that low-income women who participate in a multi-component,
      low cost-intervention delivered by a CBO will have less postpartum weight
      retention than those women who do not participate in the program. TRIAL
      REGISTRATION: The trial was retrospectively registered, ID NCT02867631, 8/11/16.

PMID- 29370796
TI  - Changes in patient-centered attitude and confidence in communicating with
      patients: a longitudinal study of resident physicians.
AB  - BACKGROUND: Patient-centered care has been one of the most frequently discussed
      principles in medical practice. However, there is a serious concern that the
      patient-centered attitudes of physicians diminish over the course of their
      medical education. This longitudinal study examined changes in resident
      physicians' patient-centered attitudes and their confidence in communicating with
      patients, and explored the relationship between the two traits. METHODS: The
      study participants were resident physicians at a university hospital in Tokyo.
      Participants' patient-centered attitudes (as measured by the Patient-Practitioner
      Orientation Scale [PPOS]), and their confidence in communicating with patients
      (as per the Physician Confidence in the Medical Interview scale: [PCMI]) were
      assessed through self-reported questionnaires completed at the beginning of
      residency (n = 204) and again at the end of the first year (n = 95). RESULTS:
      PPOS scores declined significantly during the year, both in terms of attitude
      toward sharing information and decision-making with patients, and attitude of
      caring for patients' expectations and emotions. The shift in caring attitude
      differed significantly by gender. The increase in PCMI score was greater for
      those with a smaller decrease in PPOS score. CONCLUSIONS: As seen in previous
      studies of medical students, resident physicians' patient-centered attitudes
      declined during their first year of residency, while there may be a gender-based
      difference within the shift. The increase in physicians' confidence in
      communicating with patients was greater for those who showed a smaller decline in
      patient-centered attitude. Additional studies are needed to detail the changes in
      physicians' attitudes, confidence, and communication skills over the course of
      their medical training, and to develop systematic assessment and training
      programs.

PMID- 29370797
TI  - The impact of a private sector living wage intervention on consumption and
      cardiovascular disease risk factors in a middle income country.
AB  - BACKGROUND: A positive association of socioeconomic position and health is well
      established in high-income countries. In poorer nations, however, higher income
      individuals often have more cardiovascular risk factors (including obesity) than
      do those with less income. Our study goal was to estimate the effects of
      receiving a living wage (340% higher income) on short-term changes in consumption
      and cardiovascular risk factors among low-wage workers in a middle-income
      country. METHODS: This cross-sectional study matched workers at an apparel
      factory (n=105) in the Dominican Republic with those at a similar factory (n=99)
      nearby, 15 months after the intervention factory introduced a substantially
      higher living wage. Statistical matching on non-time varying individual
      characteristics (childhood health, childhood living conditions, work experience,
      demographic factors) strengthened causal inference. Primary outcomes were blood
      pressure (systolic and diastolic), pulse rate, body mass index and waist
      circumference. Secondary outcomes were dietary consumption and spending on
      services, consumables and durable goods. RESULTS: Receiving the living wage was
      associated with increased consumption of protein, dairy, soda and juice and
      sugars, but not with cardiovascular risk factors. Intervention factory workers
      spent more on grocery items and household durable goods. CONCLUSIONS: While
      having a higher income in a middle-income country might be expected to increase
      obesity and its associated health risks, the current study found no short-term
      negative associations. There may be possible longer-term negative health
      consequences of increases in consumption of soda, juice and sugars, however. It
      is important to consider complementary interventions to support healthy dietary
      intake in areas with increasing wages.

PMID- 29370798
TI  - Barriers and prospects of India's conditional cash transfer program to promote
      institutional delivery care: a qualitative analysis of the supply-side
      perspectives.
AB  - BACKGROUND: Under the National Health Mission (NHM) of India, Janani Suraksha
      Yojana (JSY) offers conditional cash transfer and support services to pregnant
      women to use institutional delivery care facilities. This study aims to
      understand community health workers' (ASHAs) and program officials' perceptions
      regarding barriers to and prospects for the uptake of facilities offered under
      the JSY. METHODS: Fifty in-depth interviews of a purposively selected sample of
      ASHAs (n = 12), members of Village Health and Sanitation Committees (n = 11), and
      officials at different tiers of healthcare facilities (n = 27) were conducted in
      three Indian states. The data were analyzed thematically using ATLAS.ti software.
      RESULTS: Although the JSY has triggered considerable advancement on the Indian
      maternal and child health front, there are several barriers to be resolved
      pertaining to i) delivering quality care at health-facility; ii) linkages between
      home and health-facility; and iii) the community/household context. At the
      facility level, respondents cited an inability to treat birth complications as a
      barrier to JSY uptake, resulting in referrals to other (mostly private)
      facilities. Despite increased investment in health infrastructure under the
      program, shortages in emergency obstetric-care facilities, specialists and staff,
      essential drugs, diagnostics, and necessary equipment persisted. Weaker linkages
      between various vertical (standalone) elements of maternal and primary healthcare
      programs, and nearly uniform resource allocation to all facilities irrespective
      of caseloads and actual need also constrained the provision of quality
      healthcare. Barriers affecting the linkages between home and facility arose
      mainly due to the mismatch between the multiple demands and the availability of
      transport facilities, especially in emergency situations. Regarding
      community/household context, several socio-cultural issues such as resistance
      towards the ASHA's efforts of counselling, particularly from elderly family
      members, often adversely affected people's decision to seek healthcare.
      CONCLUSION: Adequate interventions at the community level, capacity building for
      healthcare providers, and measures to address underlying structural and systemic
      barriers are needed to improve the uptake of institutional maternal healthcare.

PMID- 29370799
TI  - Regulation of Locomotor activity in fed, fasted, and food-restricted mice lacking
      tissue-type plasminogen activator.
AB  - BACKGROUND: Circadian rhythms of physiology and behavior are driven by a
      circadian clock located in the suprachiasmatic nucleus of the hypothalamus. This
      clock is synchronized to environmental day/night cycles by photic input, which is
      dependent on the presence of mature brain-derived neurotrophic factor (BDNF) in
      the SCN. Mature BDNF is produced by the enzyme plasmin, which is converted from
      plasminogen by the enzyme tissue-type plasminogen activator (tPA). In this study,
      we evaluate circadian function in mice lacking functional tPA. RESULTS: tPA-/-
      mice have normal circadian periods, but show decreased nocturnal wheel-running
      activity. This difference is eliminated or reversed on the second day of a 48-h
      fast. Similarly, when placed on daily cycles of restricted food availability the
      genotypic difference in total wheel-running activity disappears, and tPA-/- mice
      show equivalent amounts of food anticipatory activity to wild type mice.
      CONCLUSIONS: These data suggest that tPA regulates nocturnal wheel-running
      activity, and that tPA differentially affects SCN-driven nocturnal activity
      rhythms and activity driven by fasting or temporal food restriction.

PMID- 29370800
TI  - A novel immortalized hepatocyte-like cell line (imHC) supports in vitro liver
      stage development of the human malarial parasite Plasmodium vivax.
AB  - BACKGROUND: Eradication of malaria is difficult because of the ability of
      hypnozoite, the dormant liver-stage form of Plasmodium vivax, to cause relapse in
      patients. Research efforts to better understand the biology of P. vivax
      hypnozoite and design relapse prevention strategies have been hampered by the
      lack of a robust and reliable model for in vitro culture of liver-stage
      parasites. Although the HC-04 hepatoma cell line is used for culturing liver
      stage forms of Plasmodium, these cells proliferate unrestrictedly and detach from
      the culture dish after several days, which limits their usefulness in a long-term
      hypnozoite assay. METHODS: A novel immortalized hepatocyte-like cell line (imHC)
      was evaluated for the capability to support P. vivax sporozoite infection. First,
      expression of basic hepatocyte markers and all major malaria sporozoite
      associated host receptors in imHC was investigated. Next, in vitro hepatocyte
      infectivity and intracellular development of sporozoites in imHC were determined
      using an indirect immunofluorescence assay. Cytochrome P450 isotype activity was
      also measured to determine the ability of imHC to metabolize drugs. Finally, the
      anti-liver-stage agent primaquine was used to test this model for a drug
      sensitivity assay. RESULTS: imHCs maintained major hepatic functions and
      expressed the essential factors CD81, SR-BI and EphA2, which are required for
      host entry and development of the parasite in the liver. imHCs could be
      maintained long-term in a monolayer without overgrowth and thus served as a good,
      supportive substrate for the invasion and growth of P. vivax liver stages,
      including hypnozoites. The observed high drug metabolism activity and potent
      responses in liver-stage parasites to primaquine highlight the potential use of
      this imHC model for antimalarial drug screening. CONCLUSIONS: imHCs, which
      maintain a hepatocyte phenotype and drug-metabolizing enzyme expression,
      constitute an alternative host for in vitro Plasmodium liver-stage studies,
      particularly those addressing the biology of P. vivax hypnozoite. They
      potentially offer a novel, robust model for screening drugs against liver-stage
      parasites.

PMID- 29370801
TI  - Expression of cocoa genes in Saccharomyces cerevisiae improves cocoa butter
      production.
AB  - BACKGROUND: Cocoa butter (CB) extracted from cocoa beans (Theobroma cacao) is the
      main raw material for chocolate production, but CB supply is insufficient due to
      the increased chocolate demand and limited CB production. CB is mainly composed
      of three different kinds of triacylglycerols (TAGs), 1,3-dipalmitoyl-2-oleoyl
      glycerol (POP, C16:0-C18:1-C16:0), 1-palmitoyl-3-stearoyl-2-oleoyl-glycerol (POS,
      C16:0-C18:1-C18:0) and 1,3-distearoyl-2-oleoyl-glycerol (SOS, C18:0-C18:1-C18:0).
      In general, Saccharomyces cerevisiae produces TAGs as storage lipids, which
      consist of C16 and C18 fatty acids. However, cocoa butter-like lipids (CBL, which
      are composed of POP, POS and SOS) are not among the major TAG forms in yeast. TAG
      biosynthesis is mainly catalyzed by three enzymes: glycerol-3-phosphate
      acyltransferase (GPAT), lysophospholipid acyltransferase (LPAT) and
      diacylglycerol acyltransferase (DGAT), and it is essential to modulate the yeast
      TAG biosynthetic pathway for higher CBL production. RESULTS: We cloned seven GPAT
      genes and three LPAT genes from cocoa cDNA, in order to screen for CBL
      biosynthetic gene candidates. By expressing these cloned cocoa genes and two
      synthesized cocoa DGAT genes in S. cerevisiae, we successfully increased total
      fatty acid production, TAG production and CBL production in some of the strains.
      In the best producer, the potential CBL content was eightfold higher than the
      control strain, suggesting the cocoa genes expressed in this strain were
      functional and might be responsible for CBL biosynthesis. Moreover, the potential
      CBL content increased 134-fold over the control Y29-TcD1 (IMX581 sct1Delta
      ale1Delta lro1Delta dga1Delta with TcDGAT1 expression) in strain Y29-441 (IMX581
      sct1Delta ale1Delta lro1Delta dga1Delta with TcGPAT4, TcLPAT4 and TcDGAT1
      expression) further suggesting cocoa GPAT and LPAT genes functioned in yeast.
      CONCLUSIONS: We demonstrated that cocoa TAG biosynthetic genes functioned in S.
      cerevisiae and identified cocoa genes that may be involved in CBL production.
      Moreover, we found that expression of some cocoa CBL biosynthetic genes improved
      potential CBL production in S. cerevisiae, showing that metabolic engineering of
      yeast for cocoa butter production can be realized by manipulating the key enzymes
      GPAT, LPAT and DGAT in the TAG biosynthetic pathway.

PMID- 29370802
TI  - Phylogenomics of the olive tree (Olea europaea) reveals the relative contribution
      of ancient allo- and autopolyploidization events.
AB  - BACKGROUND: Polyploidization is one of the major evolutionary processes that
      shape eukaryotic genomes, being particularly common in plants. Polyploids can
      arise through direct genome doubling within a species (autopolyploidization) or
      through the merging of genomes from distinct species after hybridization
      (allopolyploidization). The relative contribution of both mechanisms in plant
      evolution is debated. Here we used phylogenomics to dissect the tempo and mode of
      duplications in the genome of the olive tree (Olea europaea), one of the first
      domesticated Mediterranean fruit trees. RESULTS: Our results depict a complex
      scenario involving at least three past polyploidization events, of which two-at
      the bases of the family Oleaceae and the tribe Oleeae, respectively-are likely to
      be the result of ancient allopolyploidization. A more recent polyploidization
      involves specifically the olive tree and relatives. CONCLUSION: Our results show
      the power of phylogenomics to distinguish between allo- and auto polyploidization
      events and clarify the contributions of duplications in the evolutionary history
      of the olive tree.

PMID- 29370803
TI  - Modelling and observing the role of wind in Anopheles population dynamics around
      a reservoir.
AB  - BACKGROUND: Wind conditions, as well as other environmental conditions, are
      likely to influence malaria transmission through the behaviours of Anopheles
      mosquitoes, especially around water-resource reservoirs. Wind-induced waves in a
      reservoir impose mortality on aquatic-stage mosquitoes. Mosquitoes' host-seeking
      activity is also influenced by wind through dispersion of [Formula: see text].
      However, no malaria transmission model exists to date that simulated those
      impacts of wind mechanistically. METHODS: A modelling framework for simulating
      the three important effects of wind on the behaviours of mosquito is developed:
      attraction of adult mosquitoes through dispersion of [Formula: see text]
      ([Formula: see text] attraction), advection of adult mosquitoes (advection), and
      aquatic-stage mortality due to wind-induced surface waves (waves). The framework
      was incorporated in a mechanistic malaria transmission simulator, HYDREMATS. The
      performance of the extended simulator was compared with the observed population
      dynamics of the Anopheles mosquitoes at a village adjacent to the Koka Reservoir
      in Ethiopia. RESULTS: The observed population dynamics of the Anopheles
      mosquitoes were reproduced with some reasonable accuracy in HYDREMATS that
      includes the representation of the wind effects. HYDREMATS without the wind model
      failed to do so. Offshore wind explained the increase in Anopheles population
      that cannot be expected from other environmental conditions alone. CONCLUSIONS:
      Around large water bodies such as reservoirs, the role of wind in the dynamics of
      Anopheles population, hence in malaria transmission, can be significant.
      Modelling the impacts of wind on the behaviours of Anopheles mosquitoes aids in
      reproducing the seasonality of malaria transmission and in estimation of the risk
      of malaria around reservoirs.

PMID- 29370804
TI  - Measuring and stimulating progress on implementing widely recommended food
      environment policies: the New Zealand case study.
AB  - BACKGROUND: Monitoring the degree of implementation of widely recommended food
      environment policies by national governments is an important part of stimulating
      progress towards better population nutritional health. METHODS: The Healthy Food
      Environment Policy Index (Food-EPI) was applied for the second time in New
      Zealand in 2017 (initially applied in 2014) to measure progress on implementation
      of widely recommended food environment policies. A national panel of 71
      independent (n = 48) and government (n = 23) public health experts rated the
      extent of implementation of 47 policy and infrastructure support good practice
      indicators by the Government against international best practice, using an
      extensive evidence document verified by government officials. Experts proposed
      and prioritised concrete actions needed to address the critical implementation
      gaps identified. RESULTS: Inter-rater reliability was good (Gwet's AC2 > 0.8).
      Approximately half (47%) of the indicators were rated as having 'low' or 'very
      little, if any' implementation compared to international benchmarks, a decrease
      since 2014 (60%). A lower proportion of infrastructure support (29%) compared to
      policy (70%) indicators were rated as having 'low' or 'very little, if any'
      implementation. The experts recommended 53 actions, prioritising nine for
      immediate implementation; three of those prioritised actions were the same as in
      2014. The vast majority of experts agreed that the Food-EPI is likely to
      contribute to beneficial policy change and increased their knowledge about food
      environments and policies. CONCLUSION: The Food-EPI has the potential to increase
      accountability of governments to implement widely recommended food environment
      policies and reduce the burden of obesity and diet-related diseases.

PMID- 29370805
TI  - Molecular and physiological analysis of Anopheles funestus swarms in Nchelenge,
      Zambia.
AB  - BACKGROUND: Anopheles funestus has been recognized as a major malaria vector in
      Africa for over 100 years, but knowledge on many aspects of the biology of this
      species is still lacking. Anopheles funestus, as with most other anophelines,
      mate through swarming. A key event that is crucial for the An. funestus male to
      mate is genitalia rotation. This involves the 135 degrees  to 180 degrees 
      rotation of claspers, which are tipped with claws. This physical change then
      enables the male to grasp the female during copulation. The aim of this
      investigation was to molecularly characterize wild An. funestus swarms from
      Zambia and examine the degree of genitalia rotation within the swarm. METHODS:
      Anopheles funestus swarms were collected from Nchelenge, northern Zambia, during
      dusk periods in May 2016. All the adults from the swarm were analysed
      morphologically and identified to species level using a multiplex PCR assay.
      Anopheles funestus s.s. specimens were molecularly characterized by restriction
      fragment length polymorphism type and Clade type assays. The different stages of
      genitalia rotation were examined in the adult males. RESULTS: A total of six
      swarms were observed during the study period and between 6 and 26 mosquitoes were
      caught from each swarm. Species analysis revealed that 90% of the males from the
      swarms were An. funestus s.s. MW-type, with 84% belonging to clade I compared to
      14% clade II and 2% failed to amplify. Very few specimens (3.4%) were identified
      as Anopheles gambiae s.s. Eighty percent of the males from the swarm had complete
      genitalia rotation. CONCLUSIONS: This is the first time that An. funestus swarms
      have been molecularly identified to species level. Anopheles funestus swarms
      appear to be species-specific with no evidence of clade-type differentiation
      within these swarms. The An. funestus swarms consist mainly of males with fully
      rotated genitalia, which strongly suggests that swarming behaviour is triggered
      primarily when males have matured.

PMID- 29370807
TI  - Voltammetric analysis for fast and inexpensive diagnosis of urinary tract
      infection: a diagnostic study.
AB  - BACKGROUND: Dipstick test is widely used to support the diagnosis of urinary
      tract infections (UTI). It is effective in ruling out UTI, but urine culture is
      needed for diagnosis confirmation. In this study we compared the accuracy of
      voltammetric analysis (VA) with that of DT to detect UTI (diagnosed using urine
      culture), and its usefulness as a second-stage test in people with positive DT.
      METHODS: 142 patients were enrolled with no exclusion criteria. VA was performed
      using the BIONOTE device. Partial Least Square Discrimination Analysis was used
      to predict UTI based on VA data; diagnostic performance was evaluated using
      sensitivity, specificity, positive and negative predictive values (PPV and NPV,
      respectively), positive and negative likelihood ratios (LR), accuracy, diagnostic
      odds ratio (DOR). RESULTS: Mean age was 76.6 years (SD 12.6), 57% were male. VA
      had a better overall performance respect to DT in detecting UTI with accuracy
      81.7% vs 75.9%, specificity 90.8% vs 82.5%, PPV 75% vs 61.4%, positive LR 6.68 vs
      3.5, DOR 17.7 vs 7.47; sensibility, NPV and negative LR of the two tests were
      similar. VA had an accuracy of 82.4% in discriminating bacterial from fungal
      infections. When added as a second-stage test, VA identified 9 of the 17 false
      positive patients, with a net specificity of 91.7%, sensitivity 54%, PPV 75% and
      NPV 81%. CONCLUSIONS: VA is a quick and easy method that may be used as a second
      stage after DT to reduce the number of urine culture and of inappropriate
      antibiotic prescriptions.

PMID- 29370806
TI  - The progression rate of spinocerebellar ataxia type 2 changes with stage of
      disease.
AB  - BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) affects several neurological
      structures, giving rise to multiple symptoms. However, only the natural history
      of ataxia is well known, as measured during the study duration. We aimed to
      describe the progression rate of ataxia, by the Scale for the Assessment and
      Rating of Ataxia (SARA), as well as the progression rate of the overall
      neurological picture, by the Neurological Examination Score for Spinocerebellar
      Ataxias (NESSCA), and not only during the study duration but also in a disease
      duration model. Comparisons between these models might allow us to explore
      whether progression is linear during the disease duration in SCA2; and to look
      for potential modifiers. RESULTS: Eighty-eight evaluations were prospectively
      done on 49 symptomatic subjects; on average (SD), study duration and disease
      duration models covered 13 (2.16) months and 14 (6.66) years of individuals'
      life, respectively. SARA progressed 1.75 (CI 95%: 0.92-2.57) versus 0.79 (95% CI
      0.45 to 1.14) points/year in the study duration and disease duration models.
      NESSCA progressed 1.45 (CI 95%: 0.74-2.16) versus 0.41 (95% CI 0.24 to 0.59)
      points/year in the same models. In order to explain these discrepancies, the
      progression rates of the study duration model were plotted against disease
      duration. Then an acceleration was detected after 10 years of disease duration:
      SARA scores progressed 0.35 before and 2.45 points/year after this deadline (p =
      0.013). Age at onset, mutation severity, and presence of amyotrophy,
      parkinsonism, dystonic manifestations and cognitive decline at baseline did not
      influence the rate of disease progression. CONCLUSIONS: NESSCA and SARA
      progression rates were not constant during disease duration in SCA2: early phases
      of disease were associated with slower progressions. Modelling of future clinical
      trials on SCA2 should take this phenomenon into account, since disease duration
      might impact on inclusion criteria, sample size, and study duration. Our database
      is available online and accessible to future studies aimed to compare the present
      data with other cohorts.

PMID- 29370808
TI  - Pharmacists' role in harm reduction: a survey assessment of Kentucky community
      pharmacists' willingness to participate in syringe/needle exchange.
AB  - BACKGROUND: Pharmacists' role in harm reduction is expanding in many states, yet
      there are limited data on pharmacists' willingness to participate in harm
      reduction activities. This study assessed community pharmacists' willingness to
      participate in one harm reduction initiative: syringe/needle exchange. METHODS:
      In 2015, all Kentucky pharmacists with active licenses were emailed a survey that
      examined attitudes towards participation in syringe/needle exchange. Response
      frequencies were calculated for community pharmacist respondents. Ordinal
      logistic regression estimated the impact of community pharmacist characteristics
      and attitudes on willingness to provide clean needles/syringes to people who
      inject drugs and to dispose of used syringes/needles, where both dependent
      variables were defined as Likert-type questions on a scale of 1 (not at all
      willing) to 6 (very willing). RESULTS: Of 4699 practicing Kentucky pharmacists,
      1282 pharmacists responded (response rate = 27.3%); the majority (n = 827) were
      community pharmacists. Community pharmacists were divided on willingness to
      provide clean needles/syringes, with 39.1% not willing (score 1 or 2 of 6) and
      30% very willing (score 5 or 6 of 6). Few were willing to dispose of used
      needles/syringes, with only 18.7% willing. Community pharmacists who agreed that
      pharmacists could have significant public health impact by providing access to
      clean needles expressed 3.56 times more willingness to provide clean needles (95%
      CI 3.06-4.15), and 2.04 times more willingness to dispose of used needles (95% CI
      1.77-2.35). Chain/supermarket pharmacists (n = 485, 58.6% of community
      pharmacies) were 39% less likely to express willingness to dispose of used
      needles (95% CI 0.43-0.87) when compared with independent community pharmacists
      (n = 342, 41.4% of community pharmacies). Independent pharmacists reported
      different barriers (workflow) than their chain/supermarket pharmacist colleagues
      (concerns of clientele). CONCLUSIONS: Kentucky community pharmacists were more
      willing to provide clean needles than to dispose of used needles. Strategies to
      mitigate barriers to participation in syringe/needle exchange are warranted.

PMID- 29370809
TI  - The no-go zone: a qualitative study of access to sexual and reproductive health
      services for sexual and gender minority adolescents in Southern Africa.
AB  - BACKGROUND: Adolescents have significant sexual and reproductive health needs.
      However, complex legal frameworks, and social attitudes about adolescent
      sexuality, including the values of healthcare providers, govern adolescent access
      to sexual and reproductive health services. These laws and social attitudes are
      often antipathetic to sexual and gender minorities. Existing literature assumes
      that adolescents identify as heterosexual, and exclusively engage in
      (heteronormative) sexual activity with partners of the opposite sex/gender, so
      little is known about if and how the needs of sexual and gender minority
      adolescents are met. METHODS: In this article, we have analysed data from fifty
      in-depth qualitative interviews with representatives of organisations working
      with adolescents, sexual and gender minorities, and/or sexual and reproductive
      health and rights in Malawi, Mozambique, Namibia, Zambia and Zimbabwe. RESULTS:
      Sexual and gender minority adolescents in these countries experience double
      marginalisation in pursuit of sexual and reproductive health services: as
      adolescents, they experience barriers to accessing LGBT organisations, who fear
      being painted as "homosexuality recruiters," whilst they are simultaneously
      excluded from heteronormative adolescent sexual and reproductive health services.
      Such barriers to services are equally attributable to the real and perceived
      criminalisation of consensual sexual behaviours between partners of the same
      sex/gender, regardless of their age. DISCUSSION/ CONCLUSION: The combination of
      laws which criminalise consensual same sex/gender activity and the social stigma
      towards sexual and gender minorities work to negate legal sexual and reproductive
      health services that may be provided. This is further compounded by age-related
      stigma regarding sexual activity amongst adolescents, effectively leaving sexual
      and gender minority adolescents without access to necessary information about
      their sexuality and sexual and reproductive health, and sexual and reproductive
      health services.

PMID- 29370810
TI  - Global action for training in malaria elimination.
AB  - The Rethinking Malaria Leadership Forum, held at Harvard Business School in
      February 2017 with collaboration of the Barcelona Institute for Global Health and
      the Swiss Tropical and Public Health Institute, identified this training gap as a
      high priority for both analysis and action. The gap in human resource training
      for malaria elimination needs to be addressed in order to assure continued
      progress. This paper identifies major gaps in skills and human resources,
      suggests institutions that can assist in filling the training gaps, and proposes
      global actions to implement expanded training for malaria elimination in endemic
      countries.

PMID- 29370811
TI  - Harm, benefit and costs associated with low-dose glucocorticoids added to the
      treatment strategies for rheumatoid arthritis in elderly patients (GLORIA trial):
      study protocol for a randomised controlled trial.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the
      joints affecting 1% of the world population. It has major impact on patients
      through disability and associated comorbidities. Current treatment strategies
      have considerably improved the prognosis, but recent innovations (especially
      biologic drugs and the new class of so-called "JAK/STAT inhibitors") have
      important safety issues and are very costly. Glucocorticoids (GCs) are highly
      effective in RA, and could reduce the need for expensive treatment with biologic
      agents. However, despite more than 65 years of clinical experience, there is a
      lack of studies large enough to adequately document the benefit/harm balance. The
      result is inappropriate treatment strategies, i.e. both under-use and over-use of
      GCs, and consequently suboptimal treatment of RA. METHODS: The GLORIA study is a
      pragmatic multicentre, 2-year, randomised, double-blind, clinical trial to assess
      the safety and effectiveness of a daily dose of 5 mg prednisolone or matching
      placebo added to standard of care in elderly patients with RA. Eligible
      participants are diagnosed with RA, have inadequate disease control (disease
      activity score, DAS28 >= 2.6), and are >= 65 years. The primary outcome measures
      are the time-averaged mean value of the DAS28 and the occurrence of serious
      adverse events or adverse events of special interest. During the trial, change in
      antirheumatic therapy is permitted as clinically indicated, except for GCs. Cost
      effectiveness and cost-utility are secondary outcomes. The main challenge is the
      interpretation of the trial result with two primary endpoints and the pragmatic
      trial design that allows co-interventions. Another challenge is the definition of
      safety and the relative lack of power to detect differences between treatment
      groups. We have chosen to define safety as the number of patients experiencing at
      least one serious adverse event. We also specify a decision tree to guide our
      conclusion on the balance of benefit and harm, and our methodology to combat
      potential confounding caused by co-interventions. DISCUSSION: Pragmatic trials
      minimise impact on daily practice and maximise clinical relevance of the results,
      but analysis and interpretation of the results is challenging. We expect that the
      results of this trial are of importance for all rheumatologists who treat elderly
      patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02585258 .
      Registered on 20 October 2015.

PMID- 29370813
TI  - A randomized matched-pairs study of feasibility, acceptability, and effectiveness
      of systems consultation: a novel implementation strategy for adopting clinical
      guidelines for Opioid prescribing in primary care.
AB  - BACKGROUND: This paper reports on the feasibility, acceptability, and
      effectiveness of an innovative implementation strategy named "systems
      consultation" aimed at improving adherence to clinical guidelines for opioid
      prescribing in primary care. While clinical guidelines for opioid prescribing
      have been developed, they have not been widely implemented, even as opioid abuse
      reaches epidemic levels. METHODS: We tested a blended implementation strategy
      consisting of several discrete implementation strategies, including audit and
      feedback, academic detailing, and external facilitation. The study compares four
      intervention clinics to four control clinics in a randomized matched-pairs
      design. Each systems consultant aided clinics on implementing the guidelines
      during a 6-month intervention consisting of monthly site visits and
      teleconferences/videoconferences. The mixed-methods evaluation employs the RE-AIM
      (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework.
      Quantitative outcomes are compared using time series analysis. Qualitative
      methods included focus groups, structured interviews, and ethnographic field
      techniques. RESULTS: Seven clinics were randomly approached to recruit four
      intervention clinics. Each clinic designated a project team consisting of six to
      eight staff members, each with at least one prescriber. Attendance at
      intervention meetings was 83%. More than 80% of staff respondents agreed or
      strongly agreed with the statements: "I am more familiar with guidelines for safe
      opioid prescribing" and "My clinic's workflow for opioid prescribing is easier."
      At 6 months, statistically significant improvements were noted in intervention
      clinics in the percentage of patients with mental health screens, treatment
      agreements, urine drug tests, and opioid-benzodiazepine co-prescribing. At 12
      months, morphine-equivalent daily dose was significantly reduced in intervention
      clinics compared to controls. The cost to deliver the strategy was $7345 per
      clinic. Adaptations were required to make the strategy more acceptable for
      primary care. Qualitatively, intervention clinics reported that chronic pain was
      now treated using approaches similar to those employed for other chronic
      conditions, such as hypertension and diabetes. CONCLUSIONS: The systems
      consultation implementation strategy demonstrated feasibility, acceptability, and
      effectiveness in a study involving eight primary care clinics. This multi
      disciplinary strategy holds potential to mitigate the prevalence of opioid
      addiction and ultimately may help to improve implementation of clinical
      guidelines across healthcare. TRIAL REGISTRATION: ClinicalTrials.gov
      (NCT02433496). https://clinicaltrials.gov/ct2/show/NCT02433496 Registered May 5,
      2015.

PMID- 29370812
TI  - Atrial fibrillation in a patient with Zika virus infection.
AB  - BACKGROUND: Zika virus is an emerging arbovirus of the family Flaviviridae and
      genus Flavivirus that until 2007 was restricted to a few cases of mild illness in
      Africa and Asia. CASE PRESENTATION: We report a case of atrial fibrillation
      disclosed during an acute Zika virus infection in a 49-year-old man. Different
      biological samples were analyzed for the molecular diagnosis of Zika by real-time
      PCR, however only the saliva specimen was positive. The patient's wife tested
      positive in the serum sample, although she was an asymptomatic carrier. Moreover,
      a complete overview of patient's biomarkers, including cytokines, chemokines, and
      growth-factors levels, was analyzed and compared to gender and age matching non
      infected controls, as well as other Zika infected patients, considering the 95%CI
      of the mean values. Elevated levels of CXCL8, CCL11, CCL2, CXCL10, IL-1beta, IL
      6, TNF-alpha, IFN-gamma, IL-17, IL-1Ra, IL-4, IL-9, FGF-basic, PDGF, G-CSF, and
      GM-CSF were observed in the Atrial fibrillation patient, in contrast to
      uninfected controls. Furthermore, increased levels of CCL5, IL-1beta, TNF-alpha,
      IFN-gamma, IL-9, G-CSF, and GM-CSF were observed only in the atrial fibrillation
      patient, when compared to other Zika patients. CONCLUSIONS: To our knowledge,
      this is the first description of this type of cardiac disorder in Zika patients
      which may be considered another atypical manifestation during Zika virus
      infection.

PMID- 29370814
TI  - Concurrent renal cell carcinoma and urothelial carcinoma: long-term follow-up
      study of 27 cases.
AB  - BACKGROUND: To investigate the clinical manifestation, diagnosis, treatment, and
      outcome of simultaneous occurrence of renal cell carcinoma (RCC) and urothelial
      carcinoma. METHODS: Twenty-seven consecutive patients with synchronous renal cell
      carcinoma and urothelial carcinoma treated in two tertiary medical centers from
      March 2005 to December 2015 were retrospectively reviewed. Their clinical,
      pathological, and prognostic features were evaluated. Kaplan-Meier curves were
      used to estimate overall survival. RESULTS: The median age was 69 years (range,
      37-79 years). Seventeen patients presented with macroscopic hematuria, and 10
      patients were asymptomatic. B-ultrasound, computed tomography (CT), and
      cystoscopy initially indicated RCC concurrent with ipsilateral upper tract
      urothelial carcinoma (UTUC) in 5 cases, RCC concurrent with contralateral UTUC in
      1 case, RCC concurrent with bladder tumor in 17 cases, RCC concurrent with both
      ipsilateral UTUC and bladder tumor in 1 case, RCC in 2 cases and ureter carcinoma
      in 1 case. Different treatments were performed. The median follow-up time after
      surgery was 23 months. For patients with synchronous RCC and bladder tumor, there
      was no significant survival difference between patients treated with partial
      nephrectomy and radical nephrectomy. During follow up, four patients died of RCC,
      three patients died of non-oncological disease, one patient died of ureter
      carcinoma. The 3-year overall survival rate was 80.8%. CONCLUSIONS: Concurrence
      of RCC and urothelial carcinoma is clinically rare. Treatments should be
      individualized. The prognosis for a patient with synchronous RCC and urothelial
      carcinoma is possibly associated with the more aggressive one.

PMID- 29370815
TI  - Breast implant-associated anaplastic large cell lymphoma in a Li-FRAUMENI
      patient: a case report.
AB  - BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)
      is a rare malignancy, recently recognized as a provisional entity by the World
      Health Organization. Although increasing data have been published on this entity
      in recent years, a great number of patients and health professionals remain
      unaware of this diagnosis. CASE PRESENTATION: We herein report the case of a 56
      year-old female with Li-FRAUMENI syndrome who presented with late right-sided
      recurrent breast swelling after prophylactic adenomastectomy with implant
      reconstruction. Imaging scans revealed an heterogeneous mass adjacent to the
      implant fibrous capsule. A biopsy of the lesion rendered the diagnosis of a BIA
      ALCL. CONCLUSIONS: This case presents similarities with previous reports, but
      also some particularities, which should be stressed in order to make the
      diagnosis the earliest possible. The most distinct feature is that this is the
      second report of BIA-ALCL arising in the setting of Li-FRAUMENI syndrome.

PMID- 29370816
TI  - Prevalence of lower limb deep venous thrombosis among adult HIV positive patients
      attending an outpatient clinic at Mulago Hospital.
AB  - BACKGROUND: Deep venous thrombosis (DVT) and its major complication pulmonary
      embolism (PE) are collectively known as venous thromboembolism. In Uganda, the
      prevalence of DVT among HIV patients has not been previously published. The aim
      of the study was to determine the prevalence and sonographic features of lower
      limb deep venous thrombosis among HIV positive patients on anti-retroviral
      treatment (ART). METHODS: This was a cross sectional study in which HIV positive
      patients on ART were recruited from an out-patient HIV clinic at Mulago National
      Referral Hospital. Patients were randomly selected and enrolled until a sample
      size of 384 was reached. Study participants underwent compression and Doppler
      ultrasound studies of both lower limb deep veins using Medison Sonoacer7
      ultrasound machine. RESUTS: We found a prevalence of DVT of 9.1% (35 of 384
      participants) among HIV patients on ART. The prevalence of latent (asymptomatic)
      DVT was 2.3%. Among 35 patients with DVT, 42.8% had chronic DVT; 31.1% had acute
      DVT and the rest had latent DVT. Among the risk factors, the odds of occurrence
      of DVT among patients with prolonged immobility were 4.81 times as high as in
      those with no prolonged immobility (p = 0.023; OR = 4.81; 95% CI 1.25-18.62).
      Treatment with second line anti-retroviral therapy (ART) including protease
      inhibitors (PIs) was associated with higher odds of DVT occurrence compared with
      first line ART (p = 0.020; OR = 2.38; 95% CI 1.14-4.97). The odds of DVT
      occurrence in patients with a lower CD4 count (< 200 cells/ul) were 5.36 times as
      high as in patients with CD4 counts above 500 cells/ul (p = 0.008). About 48.6%
      patients with DVT had a low risk according to Well's score. CONCLUSION: DVT was
      shown in nearly 10% of HIV patients attending an out-patient clinic in an urban
      setting in Uganda. Risk factors included protease inhibitors in their ART
      regimen, prolonged immobility, and low CD4 count (< 200 cells/ul). Clinicians
      should have a low threshold for performing lower limb Doppler ultrasound scan
      examination on infected HIV patients on ART who are symptomatic for DVT.
      Therefore, clinicians should consider anti-coagulant prophylaxis and lower deep
      venous ultrasound screening of patients who are on second line ART regimen with
      low CD4 cell counts and/or with prolonged immobility or hormonal contraception.

PMID- 29370817
TI  - Establishment and genomic characterizations of patient-derived esophageal
      squamous cell carcinoma xenograft models using biopsies for treatment
      optimization.
AB  - BACKGROUND: Squamous cell carcinoma is the dominant type of esophageal cancer in
      China with many patients initially diagnosed at advanced stage. Patient-derived
      xenografts (PDX) models have been developed to be an important platform for
      preclinical research. This study aims to establish and characterize PDX models
      using biopsy tissue from advanced esophageal cancer patients to lay the
      foundation of preclinical application. METHODS: Fresh endoscopic biopsy tissues
      were harvested from patients with advanced esophageal cancer and implanted
      subcutaneously into NOD/SCID mice. Then, the PDXs were serially passaged for up
      to four generations. Transplantation was analyzed and genomic characteristics of
      xenografts were profiled using next-generation sequencing. RESULTS: Twenty-five
      PDX models were established (13.3%, 25/188). The latency period was 75.12 +/-
      19.87 days (50-120 days) for the first passage and it decreased with increasing
      passaging. Other than tumor stages, no differences were found between
      transplantations of xenografts and patient characteristics, irrespective of
      chemotherapy. Histopathological features and chemosensitivity of PDXs were in
      great accordance with primary patient tumors. Each PDX was assessed for molecular
      characteristics including copy number variations, somatic mutations, and
      signaling pathway abnormalities and these were similar to patient results.
      CONCLUSIONS: Our PDX models were established from real time biopsies and
      molecularly profiled. They might be promising for drug development and
      individualized therapy.

PMID- 29370818
TI  - The effects of an activity-based lifestyle intervention on moderate sleep
      complaints among older adults: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Moderate sleep complaints are major gerontological issue affecting as
      many as 80% of older adults. More intriguing findings have indicated that
      moderate sleep complaints were associated with cognitive decline, functional
      deterioration, clinical depression, and even morbidity and mortality among older
      adults. The aim of this study is to evaluate the effects of an activity-based
      lifestyle intervention on moderate sleep complaint among community-dwelling older
      adults. METHODS/DESIGN: This sequential quantitative-qualitative mixed method
      study will randomly allocate 224 individuals to receive either the 16-week group
      based moderate-intensity stepping exercise or 16-week health education. The
      exercise group receives three 60-min stepping exercises per week, whereas the
      education group receives weekly educative talks on health topics other than
      sleep. The primary outcomes are sleep quality as measured by the Pittsburgh Sleep
      Quality Index (PSQI) and sleep pattern as measured by the actiwatch. Physical
      fitness and mood status are measured as mediating variables by using the Rockport
      walking test and Profile of Mood States. The qualitative part will invite 30
      individuals from the exercise group who have different sleep-related treatment
      responses to participate in individual interviews to explore their overall
      perception of using stepping exercise as a lifestyle intervention to improve
      sleep. Mixed effects model with intention-to-treat analysis will be used for
      quantitative data. Inductive thematic analysis with a prior coding framework will
      be used for the qualitative data. DISCUSSION: By investigating the effects and
      the mediating mechanism of a moderate-intensity exercise program on moderate
      sleep complaints among older adults, this study will generate evidence of high
      scientific value and important public health implication. Understanding the sleep
      promoting effects and acceptability of exercise informs how to apply lifestyle
      promotion as a public health practice to improve late-life moderate sleep
      complaints and forestall its progression to level of clinical severity. TRIAL
      REGISTRATION: Clinical Trial Registry Team, Center for Clinical Research and
      Biostatistics CUHK, CCRB00491 . Registered on 1 December 2015.

PMID- 29370819
TI  - Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone
      furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive
      pulmonary disease: a randomized non-inferiority study.
AB  - BACKGROUND: Single-inhaler fluticasone furoate/umeclidinium/vilanterol
      (FF/UMEC/VI) 100/62.5/25 MUg has been shown to improve lung function and health
      status, and reduce exacerbations, versus budesonide/formoterol in patients with
      chronic obstructive pulmonary disease (COPD). We evaluated the non-inferiority of
      single-inhaler FF/UMEC/VI versus FF/VI + UMEC using two inhalers. METHODS:
      Eligible patients with COPD (aged >=40 years; >=1 moderate/severe exacerbation in
      the 12 months before screening) were randomized (1:1; stratified by the number of
      long-acting bronchodilators [0, 1 or 2] per day during run-in) to receive 24-week
      FF/UMEC/VI 100/62.5/25 MUg and placebo or FF/VI 100/25 MUg + UMEC 62.5 MUg; all
      treatments/placebo were delivered using the ELLIPTA inhaler once-daily in the
      morning. Primary endpoint: change from baseline in trough forced expiratory
      volume in 1 s (FEV1) at Week 24. The non-inferiority margin for the lower 95%
      confidence limit was set at - 50 mL. RESULTS: A total of 1055 patients (844 [80%]
      of whom were enrolled on combination maintenance therapy) were randomized to
      receive FF/UMEC/VI (n = 527) or FF/VI + UMEC (n = 528). Mean change from baseline
      in trough FEV1 at Week 24 was 113 mL (95% CI 91, 135) for FF/UMEC/VI and 95 mL
      (95% CI 72, 117) for FF/VI + UMEC; the between-treatment difference of 18 mL (95%
      CI -13, 50) confirmed FF/UMEC/VI's was considered non-inferior to FF/VI + UMEC.
      At Week 24, the proportion of responders based on St George's Respiratory
      Questionnaire Total score was 50% (FF/UMEC/VI) and 51% (FF/VI + UMEC); the
      proportion of responders based on the Transitional Dyspnea Index focal score was
      similar (56% both groups). A similar proportion of patients experienced a
      moderate/severe exacerbation in the FF/UMEC/VI (24%) and FF/VI + UMEC (27%)
      groups; the hazard ratio for time to first moderate/severe exacerbation with
      FF/UMEC/VI versus FF/VI + UMEC was 0.87 (95% CI 0.68, 1.12). The incidence of
      adverse events was comparable in both groups (48%); the incidence of serious
      adverse events was 10% (FF/UMEC/VI) and 11% (FF/VI + UMEC). CONCLUSIONS: Single
      inhaler triple therapy (FF/UMEC/VI) is non-inferior to two inhalers (FF/VI +
      UMEC) on trough FEV1 change from baseline at 24 weeks. Results were similar on
      all other measures of efficacy, health-related quality of life, and safety. TRIAL
      REGISTRATION: GSK study CTT200812; ClinicalTrials.gov NCT02729051 (submitted 31
      March 2016).

PMID- 29370820
TI  - Quality improvement as a framework for behavior change interventions in HIV
      predisposed communities: a case of adolescent girls and young women in northern
      Uganda.
AB  - BACKGROUND: Despite the conventional approaches to HIV prevention being the
      bedrock for early reductions in HIV infections in Uganda, innovations that
      demonstrate reduction in risk to infection in vulnerable populations need to be
      embraced urgently. In the past 2 years, a USAID-funded project tested a quality
      improvement for behavior change model (QBC) to address barriers to behavioral
      change among adolescent girls and young women (AGYW) at high risk of HIV
      infection. The model comprised skills building to improve ability of AGYW to stop
      risky behavior; setting up and empowering community quality improvement (QI)
      teams to mobilize community resources to support AGYW to stop risky behavior; and
      service delivery camps to provide HIV prevention services and commodities to AGYW
      and other community members. METHODS: We recruited and followed a cohort of 409
      AGYW at high risk of HIV infection over a 2-year period to examine the effect of
      the QBC model on risky behaviors. High-risk behavior was defined to include
      transactional sex, having multiple sexual partners, and non-use of condoms in
      high-risk sex. We documented unique experiences over the period to assess the
      effect of QBC model in reducing risky behavior. We analyzed for variances in risk
      factors over time using repeated measures ANOVA. RESULTS: There were
      statistically significant declines in high-risk behavior among AGYW over the QBC
      roll-out period (p < 0.05). Univariate analysis indicated reduction in AGYW
      reporting multiple sexual partners from 16.6% at baseline to 3.2% at follow up
      and transactional sex from 13.2 to 3.6%. The proportion of AGYW experiencing
      sexual and other forms of gender based violence reduced from 49% a baseline to
      19.5% at follow up due to the complementary targeting of parents and partners by
      QI teams. CONCLUSION: The QBC model is appropriate for the context of northern
      Uganda because it provides a framework for the community to successfully drive
      HIV prevention efforts and therefore is recommended as a model for HIV prevention
      in high-risk groups.

PMID- 29370821
TI  - PhenoDis: a comprehensive database for phenotypic characterization of rare
      cardiac diseases.
AB  - BACKGROUND: Thoroughly annotated data resources are a key requirement in
      phenotype dependent analysis and diagnosis of diseases in the area of precision
      medicine. Recent work has shown that curation and systematic annotation of human
      phenome data can significantly improve the quality and selectivity for the
      interpretation of inherited diseases. We have therefore developed PhenoDis, a
      comprehensive, manually annotated database providing symptomatic, genetic and
      imprinting information about rare cardiac diseases. RESULTS: PhenoDis includes
      214 rare cardiac diseases from Orphanet and 94 more from OMIM. For phenotypic
      characterization of the diseases, we performed manual annotation of diseases with
      articles from the biomedical literature. Detailed description of disease symptoms
      required the use of 2247 different terms from the Human Phenotype Ontology (HPO).
      Diseases listed in PhenoDis frequently cover a broad spectrum of symptoms with
      28% from the branch of 'cardiovascular abnormality' and others from areas such as
      neurological (11.5%) and metabolism (6%). We collected extensive information on
      the frequency of symptoms in respective diseases as well as on disease-associated
      genes and imprinting data. The analysis of the abundance of symptoms in patient
      studies revealed that most of the annotated symptoms (71%) are found in less than
      half of the patients of a particular disease. Comprehensive and systematic
      characterization of symptoms including their frequency is a pivotal prerequisite
      for computer based prediction of diseases and disease causing genetic variants.
      To this end, PhenoDis provides in-depth annotation for a complete group of rare
      diseases, including information on pathogenic and likely pathogenic genetic
      variants for 206 diseases as listed in ClinVar. We integrated all results in an
      online database ( http://mips.helmholtz-muenchen.de/phenodis/ ) with multiple
      search options and provide the complete dataset for download. CONCLUSION:
      PhenoDis provides a comprehensive set of manually annotated rare cardiac diseases
      that enables computational approaches for disease prediction via decision support
      systems and phenotype-driven strategies for the identification of disease causing
      genes.

PMID- 29370822
TI  - Slowly progressive dementia caused by MAPT R406W mutations: longitudinal report
      on a new kindred and systematic review.
AB  - BACKGROUND: The MAPT c.1216C > T (p.Arg406Trp; R406W) mutation is a known cause
      of frontotemporal dementia with Parkinsonism linked to chromosome 17 tau with
      Alzheimer's disease-like clinical features. METHODS: We compiled clinical data
      from a new Swedish kindred with R406W mutation. Seven family members were
      followed longitudinally for up to 22 years. Radiological examinations were
      performed in six family members and neuropathological examinations in three. We
      systematically reviewed the literature and compiled clinical, radiological, and
      neuropathological data on 63 previously described R406W heterozygotes and 3
      homozygotes. RESULTS: For all cases combined, the median age of onset was 56
      years and the median disease duration was 13 years. Memory impairment was the
      most frequent symptom, behavioral disturbance and language impairment were less
      common, and Parkinsonism was rare. Disease progression was most often slow. The
      most frequent clinical diagnosis was Alzheimer's disease. R406W homozygotes had
      an earlier age at onset and a higher frequency of behavioral symptoms and
      Parkinsonism than heterozygotes. In the new Swedish kindred, a consistent imaging
      finding was ventromedial temporal lobe atrophy, which was evident also in early
      disease stages as a widening of the collateral sulcus with ensuing atrophy of the
      parahippocampal gyrus. Unlike previously published R406W carriers, all three
      autopsied patients from the novel family showed neuropathological similarities
      with progressive supranuclear palsy, with predominant four-repeat (exon 10+) tau
      isoform (4R) tauopathy and neurofibrillary tangles accentuated in the basal
      medial temporal lobe. Amyloid-beta pathology was absent. CONCLUSIONS: Dominance
      of 4R over three-repeat (exon 10-) tau isoforms contrasts with earlier reports of
      R406W patients and was not sufficiently explained by the presence of H1/H2
      haplotypes in two of the autopsied patients. R406W patients often show a long
      course of disease with marked memory deficits. Both our neuropathological results
      and our imaging findings revealed that the ventromedial temporal lobes were
      extensively affected in the disease. We suggest that this area may represent the
      point of origin of tau deposition in this disease with relatively isolated
      tauopathy.

PMID- 29370823
TI  - Identification of protein lysine methylation readers with a yeast three-hybrid
      approach.
AB  - BACKGROUND: Protein posttranslational modifications (PTMs) occur broadly in the
      human proteome, and their biological outcome is often mediated indirectly by
      reader proteins that specifically bind to modified proteins and trigger
      downstream effects. Particularly, many lysine methylation sites among histone and
      nonhistone proteins have been characterized; however, the list of readers
      associated with them is incomplete. RESULTS: This study introduces a modified
      yeast three-hybrid system (Y3H) to screen for methyllysine readers. A lysine
      methyltransferase is expressed together with its target protein or protein domain
      functioning as bait, and a human cDNA library serves as prey. Proof of principle
      was established using H3K9me3 as a bait and known H3K9me3 readers like the
      chromodomains of CBX1 or MPP8 as prey. We next conducted an unbiased screen using
      a library composed of human-specific open reading frames. It led to the
      identification of already known lysine methylation-dependent readers and of novel
      methyllysine reader candidates, which were further confirmed by co-localization
      with H3K9me3 in human cell nuclei. CONCLUSIONS: Our approach introduces a cost
      effective method for screening reading domains binding to histone and nonhistone
      proteins which is not limited by expression levels of the candidate reading
      proteins. Identification of already known and novel H3K9me3 readers proofs the
      power of the Y3H assay which will allow for proteome-wide screens of PTM readers.

PMID- 29370824
TI  - Home-based physical activity incentive and education program in subacute phase of
      stroke recovery (Ticaa'dom): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Stroke causes functional decline, psychological disorders and
      cognitive impairments that affect activities of daily living and quality of life.
      Although physical activity (PA) is beneficial in stroke recovery, PA
      recommendations are rarely met after hospital discharge. There is presently no
      standard strategy for monitoring and inciting PA at home during the subacute
      phase of stroke recovery. The main aim of this study is to evaluate the effects
      of a home-based physical activity incentive and education program (Ticaa'dom) on
      functional capacity in subacute stroke patients. METHODS: This study is a
      comparative prospective, observer-blinded, monocentric, parallel, randomized
      controlled clinical trial. This study will include 84 patients: 42 patients in
      the home-based physical activity incentive group (HB-PAI) and 42 in the control
      group (CG). The intervention group will follow the HB-PAI program over 6 months:
      their PA will be monitored with an accelerometer during the day at home while
      they record their subjective perception of PA on a chart; they will observe a
      weekly telephone call and a home visit every three weeks. The CG will receive
      traditional medical care over 12 months. The main study outcome will be the
      distance on a 6-minute walk test. Secondary outcomes will include measurements of
      lower limb strength, independence level, body composition, cardiac analysis,
      fatigue and depression state. DISCUSSION: The results of this trial will
      demonstrate the value of implementing the Ticaa'dom program during the subacute
      phase of stroke recovery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01822938 .
      Registered on 25 March 2013.

PMID- 29370825
TI  - A novel language-neutral Visual Cognitive Assessment Test (VCAT): validation in
      four Southeast Asian countries.
AB  - BACKGROUND: Cognitive screeners are imperative for early diagnosis of dementia.
      The Visual Cognitive Assessment Test (VCAT) is a language-neutral, visual-based
      test which has proven useful for a multilingual population in a single-center
      study. However, its performance utility is unknown in a wider and more diverse
      Southeast Asian cohort. METHODS: We recruited 164 healthy controls (HC) and 120
      cognitively impaired (CI) subjects- 47 mild cognitive impairment (MCI) and 73
      mild Alzheimer's disease (AD) dementia participants, from four countries between
      January 2015 and August 2016 to determine the usefulness of a single version of
      the VCAT, without translation or adaptation, in a multinational, multilingual
      population. The VCAT was administered along with established cognitive
      evaluation. RESULTS: The VCAT, without local translation or adaptation, was
      effective in discriminating between HC and CI subjects (MCI and mild AD
      dementia). Mean (SD) VCAT scores for HC and CI subjects were 22.48 (3.50) and
      14.17 (5.05) respectively. Areas under the curve for Montreal Cognitive
      Assessment (0.916, 95% CI 0.884-0.948) and the VCAT (0.905, 95% CI 0.870-0.940)
      in discriminating between HCs and CIs were comparable. The multiple languages
      used to administer VCAT in four countries did not significantly influence test
      scores. CONCLUSIONS: The VCAT without the need for language translation or
      cultural adaptation showed satisfactory discriminative ability and was effective
      in a multinational, multilingual Southeast Asian population.

PMID- 29370826
TI  - BANK1 alters B cell responses and influences the interactions between B cells and
      induced T regulatory cells in mice with collagen-induced arthritis.
AB  - BACKGROUND: Functional variants of the B cell gene, B cell scaffold protein with
      ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility,
      but their influences on B cell responses are unclear. Moreover, the function of
      induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen
      induced arthritis (CIA) model is unknown. This study was performed to investigate
      the roles of BANK1 in CIA and the interaction between B cells and iTregs.
      METHODS: The changes in BANK1 mRNA and protein levels and their correlation with
      disease severity in CIA were determined. Next, the antigen-presenting function
      and autoantibody production in B cells were evaluated by co-culture with effector
      T cells and iTregs, respectively, both in vitro and in vivo. Then, the mechanisms
      underlying these interactions were studied by adding neutralizing antibodies or
      transwell inserts and by adoptive transfer to B-cell-depleted CIA mice. RESULTS:
      The BANK1 level decreased in the peripheral blood, spleen and lymph nodes of CIA
      mice, particularly during the acute stage of arthritis, and exhibited negative
      correlation with disease severity and autoantibody production. B cell responses
      were enhanced by this decrease. B cells from CIA mice (CIA-B cells) promoted
      iTreg differentiation, proliferation and cytotoxic T lymphocyte-associated
      protein-4 (CTLA-4) expression. Meanwhile, BANK1 expression in CIA-B cells
      increased after co-culture with iTregs, limiting B cell responses. All these
      interactions depended on cell contact with CTLA-4-overexpressing iTregs but were
      independent of CTLA-4 cytokine. CONCLUSION: Decreased BANK1 expression promotes B
      cell responses, resulting in an increased antigen presentation ability and
      autoantibody production that subsequently influences the communication between B
      cells and iTregs through a cell-contact-dependent and CTLA-4- cytokine
      independent mechanism in CIA mice.

PMID- 29370828
TI  - Prevalence and antimicrobial susceptibility pattern of Salmonella and Shigella
      species among asymptomatic food handlers working in Haramaya University
      cafeterias, Eastern Ethiopia.
AB  - OBJECTIVE: Salmonellosis and Shigellosis remain a major public health problem
      across the globe, particularly in developing countries like Ethiopia, where hand
      hygiene and food microbiology are still below the required standards. The growing
      problem of antimicrobial resistance species also continues to pose public health
      challenges. This study assessed the prevalence and antimicrobial susceptibility
      pattern of Salmonella and Shigella species among asymptomatic food handlers. A
      cross-sectional study was conducted among 417 randomly selected asymptomatic food
      handlers. Data were collected using a structured questionnaire. The stool
      specimens collected were examined for Salmonella and Shigella species using
      standard bacteriological methods. Descriptive statistics were used to describe
      the basic features of the data. RESULTS: The overall prevalence of Salmonella and
      Shigella species was 5.04%. Salmonella and Shigella species were 76.2% resistant
      to both co-trimoxazole and tetracycline, 71.4% to amoxicillin and 66.7% to
      chloramphenicol. Moreover, 85.7% of Salmonella and Shigella species were
      multidrug resistant. The findings highlighted the food handlers as potential
      sources of food borne infections, which demands the establishment of appropriate
      hygiene and sanitary control measures at the University cafeterias.

PMID- 29370827
TI  - Impact of question order on prioritisation of outcomes in the development of a
      core outcome set: a randomised controlled trial.
AB  - BACKGROUND: Core outcome set (COS) developers increasingly employ Delphi surveys
      to elicit stakeholders' opinions of which outcomes to measure and report in
      trials of a particular condition or intervention. Research outside of Delphi
      surveys and COS development demonstrates that question order can affect response
      rates and lead to 'context effects', where prior questions determine an item's
      meaning and influence responses. This study examined the impact of question order
      within a Delphi survey for a COS for oesophageal cancer surgery. METHODS: A
      randomised controlled trial was nested within the Delphi survey. Patients and
      health professionals were randomised to receive a survey including clinical and
      patient-reported outcomes (PROs), where the PRO section appeared first or last.
      Participants rated (1-9) the importance of 68 items for inclusion in a COS
      (ratings 7-9 considered 'essential'). Analyses considered the impact of question
      order on: (1) survey response rates; (2) participants' responses; and (3) items
      retained at end of the survey. RESULTS: In total, 116 patients and 71
      professionals returned completed surveys. Question order did not affect response
      rates among patients, but fewer professionals responded when clinical items
      appeared first (difference = 31.3%, 95% confidence interval [CI] = 13.6-48.9%, P
      = 0.001). Question order led to different context effects within patients and
      professionals. While patients rated clinical items highly, irrespective of
      question order, more PROs were rated essential when appearing last rather than
      first (difference = 23.7%, 95% CI = 10.5-40.8%). Among professionals, the
      greatest impact was on clinical items; a higher percentage rated essential when
      appearing last (difference = 11.6%, 95% CI = 0.0-23.3%). An interaction between
      question order and the percentage of PRO/clinical items rated essential was
      observed for patients (P = 0.025) but not professionals (P = 0.357). Items
      retained for further consideration at the end of the survey were dependent on
      question order, with discordant items (retained by one question order group only)
      observed in patients (18/68 [26%]) and professionals (20/68 [29%]). CONCLUSIONS:
      In the development of a COS, participants' ratings of potential outcomes within a
      Delphi survey depend on the context (order) in which the outcomes are asked,
      consequently impacting on the final COS. Initial piloting is recommended with
      consideration of the randomisation of items in the survey to reduce potential
      bias. TRIAL REGISTRATION: The randomised controlled trial reported within this
      paper was nested within the development of a core outcome set to investigate
      processes in core outcome set development. Outcomes were not health-related and
      trial registration was not therefore applicable.

PMID- 29370829
TI  - Text4Heart II - improving medication adherence in people with heart disease: a
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Cardiac rehabilitation (CR) is an essential component of contemporary
      management for patients with coronary heart disease, including following an acute
      coronary syndrome (ACS). CR typically involves education and support to assist
      people following an ACS to make lifestyle changes and prevent subsequent events.
      Despite its benefits, uptake and participation in tradition CR programs is low.
      The use of mobile technologies (mHealth) offers the potential to improve reach,
      access, and delivery of CR support. We aim to determine the effectiveness and
      cost-effectiveness of a text-messaging intervention (Text4Heart II) to improve
      adherence to medication and lifestyle change in addition to usual care in people
      following an ACS. A second aim is to use the RE-AIM framework to inform the
      potential implementation of Text4Heart II within health services in New Zealand.
      METHODS: Text4Heart II is a two-arm, parallel, superiority randomized controlled
      trial conducted in two large metropolitan hospitals in Auckland, New Zealand.
      Three hundred and thirty participants will be randomized to either a 24-week
      theory- and evidence-based personalized text message program to support self
      management in addition to usual CR, or usual CR alone (control). Outcomes are
      assessed at 6 and 12 months. The primary outcome is the proportion of
      participants adhering to medication at 6 months as measured by dispensed records.
      Secondary outcomes include medication adherence at 12 months, the proportion of
      participants adhering to self-reported healthy behaviors (physical activity,
      fruit and vegetable consumption, moderating alcohol intake and smoking status)
      measured using a composite health behavior score, self-reported medication
      adherence, cardiovascular risk factors (lipids, blood pressure), readmissions and
      related hospital events at 6 and 12 months. A cost-effectiveness analysis will
      also be conducted. Using the RE-AIM framework, we will determine uptake and
      sustainability of the intervention. DISCUSSION: The Text4Heart II trial will
      determine the effectiveness of a text-messaging intervention to improve adherence
      to medication and lifestyle behaviors at both 6 and 12 months. Using the RE-AIM
      framework this trial will provide much needed data and insight into the potential
      implementation of Text4Heart II. This trial addresses many limitations/criticisms
      of previous mHealth trials; it builds on our Text4Heart pilot trial, it is
      adequately powered, has sufficient duration to elicit behavior change, and the
      follow-up assessments (6 and 12 months) are long enough to determine the
      sustained effect of the intervention. TRIAL REGISTRATION: Australian New Zealand
      Clinical Trials Registry, ID: ACTRN12616000422426 . Registered retrospectively on
      1 April 2016.

PMID- 29370830
TI  - A comparison of meta-analytic methods for synthesizing evidence from explanatory
      and pragmatic trials.
AB  - BACKGROUND: The pragmatic-explanatory continuum indicator summary version 2
      (PRECIS-2) tool has recently been developed to classify randomized clinical
      trials (RCTs) as pragmatic or explanatory based on their design characteristics.
      Given that treatment effects in explanatory trials may be greater than those
      obtained in pragmatic trials, conventional meta-analytic approaches may not
      accurately account for the heterogeneity among the studies and may result in
      biased treatment effect estimates. This study investigates if the incorporation
      of PRECIS-2 classification of published trials can improve the estimation of
      overall intervention effects in meta-analysis. METHODS: Using data from 31
      published trials of intervention aimed at reducing obesity in children, we
      evaluated the utility of incorporating PRECIS-2 ratings of published trials into
      meta-analysis of intervention effects in clinical trials. Specifically, we
      compared random-effects meta-analysis, stratified meta-analysis, random-effects
      meta-regression, and mixture random-effects meta-regression methods for
      estimating overall pooled intervention effects. RESULTS: Our analyses revealed
      that mixture meta-regression models that incorporate PRECIS-2 classification as
      covariate resulted in a larger pooled effect size (ES) estimate (ES = - 1.01,
      95%CI = [- 1.52, - 0.43]) than conventional random-effects meta-analysis (ES = -
      0.15, 95%CI = [- 0.23, - 0.08]). CONCLUSIONS: In addition to the original intent
      of PRECIS-2 tool of aiding researchers in their choice of trial design, PRECIS-2
      tool is useful for explaining between study variations in systematic review and
      meta-analysis of published trials. We recommend that researchers adopt mixture
      meta-regression methods when synthesizing evidence from explanatory and pragmatic
      trials.

PMID- 29370831
TI  - The impact of financial incentives on physical activity in adults: a systematic
      review protocol.
AB  - BACKGROUND: Most adults fail to meet global physical activity guidelines set out
      by the World Health Organization. In recent years, behavioural economic
      principles have been used to design novel interventions that increase physical
      activity. Immediate financial rewards, for instance, can motivate an individual
      to change physical activity behaviour by lowering the opportunity costs of
      exercise. This systematic review will summarise the evidence about the
      effectiveness of financial incentive interventions for improving physical
      activity in adults. METHODS: We will search MEDLINE, Embase, Cochrane Central
      Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health
      Literature, Web of Science, Scopus, PsycINFO, EconLit, SPORTDiscus, the National
      Health Service Economic Evaluation Database, ClinicalTrials.gov and the World
      Health Organization International Clinical Trials Registry Platform from
      inception using a comprehensive, electronic search strategy. The search strategy
      will include terms related to 'financial incentive' and 'physical activity'. Only
      randomised controlled trials that investigate the effect of financial incentives
      on physical activity in adult populations and that are written in the English
      language will be included. Two review authors will independently screen abstracts
      and titles, complete full text reviews and extract data on objective and self
      reported physical activity outcomes. The authors will also assess the study
      quality using the Cochrane risk of bias tool and provide a systematic
      presentation and synthesis of the included studies' characteristics and results.
      If more than two studies are sufficiently similar in population, settings and
      interventions, we will pool the data to conduct a meta-analysis. If we are unable
      to perform a meta-analysis, we will conduct a narrative synthesis of the results
      and produce forest plots for individual studies. Our subgroup analyses will
      examine the differential effects of an intervention in healthy populations
      compared to populations with disease pathology and compare the effects of
      interventions using financial rewards to interventions using financial penalties.
      DISCUSSION: This systematic review will determine the effectiveness of positive
      and negative financial incentives on physical activity in adults. Findings will
      help inform the development of public health interventions and research in this
      field. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2017: CRD42017068263.

PMID- 29370832
TI  - Children's, parents' and other stakeholders' perspectives on early dietary self
      management to delay disease progression of chronic disease in children: a
      protocol for a mixed studies systematic review with a narrative synthesis.
AB  - BACKGROUND: Chronic disease of childhood may be delayed by early dietary
      intervention. The purpose of this systematic review is to provide decision-makers
      with a perspective on the role of early dietary intervention, as a form of self
      management, to delay disease progression in children with early chronic disease,
      as described by children, parents and other stakeholders. METHODS: The study will
      systematically review empirical research (qualitative, quantitative and mixed
      method designs), including grey literature, using a narrative synthesis. A four
      stage search process will be conducted involving a scoping search, the Scottish
      Intercollegiate Guidelines Network (SIGN) Patient Issues search filter on
      MEDLINE, the search of seven databases using a chronic disease and chronic kidney
      disease (CKD) search strategy, and hand searching the reference lists of
      identified papers for additional studies. All studies retrieved during the search
      process will undergo a screening and selection process against the
      inclusion/exclusion criteria. Methodological quality of relevant studies will be
      assessed using a validated Mixed Studies Review scoring system, before inclusion
      in the review. Relevant grey literature will be assessed for methodological
      quality and relative importance using McGrath et al.'s framework and the Academy
      Health advisory committee categories, respectively. Data extraction will be
      guided by the Centre for Review and Dissemination guidance and Popay et al.'s
      work. The narrative synthesis of the findings will use elements of Popay et al.'s
      methodology of narrative synthesis, applying recognised tools for each of the
      four elements: (1) developing a theory of how the intervention works, why and for
      whom; (2) developing a preliminary synthesis of findings of included studies; (3)
      exploring relationships in the data; and (4) assessing the robustness of the
      synthesis. DISCUSSION: This mixed studies systematic review with a narrative
      synthesis seeks to elucidate the gaps in current knowledge and generate a fresh
      explanation of research findings on early dietary self-management in chronic
      disease, with particular application to CKD, from the stakeholders' perspective.
      The review will provide an important platform to inform future research,
      identifying the facilitators and barriers to implementing early dietary
      interventions. Ultimately, the review will contribute vital information to inform
      future improvements in chronic disease. The lead author has a particular interest
      in CKD paediatric service delivery. SYSTEMATIC REVIEW REGISTRATION: The review
      has been registered with PROSPERO (CRD42017078130).

PMID- 29370833
TI  - Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal
      Alzheimer's disease.
AB  - BACKGROUND: We investigated whether a panel of 12 potential novel biomarkers
      consisting of proteins involved in synapse functioning and immunity would be able
      to distinguish patients with Alzheimer's disease (AD) and patients with mild
      cognitive impairment (MCI) from control subjects. METHODS: We included 40 control
      subjects, 40 subjects with MCI, and 40 subjects with AD from the Amsterdam
      Dementia Cohort who were matched for age and sex (age 65 +/- 5 years, 19 [48%]
      women). The mean follow-up of patients with MCI was 3 years. Two or three tryptic
      peptides per protein were analyzed in cerebrospinal fluid using parallel reaction
      monitoring mass spectrometry. Corresponding stable isotope-labeled peptides were
      added and used as reference peptides. Multilevel generalized estimating equations
      (GEEs) with peptides clustered per subject and per protein (as within-subject
      variables) were used to assess differences between diagnostic groups. To assess
      differential effects of individual proteins, we included the diagnosis * protein
      interaction in the model. Separate GEE analyses were performed to assess
      differences between stable patients and patients with progressive MCI (MCI-AD).
      RESULTS: There was a main effect for diagnosis (p < 0.01) and an interaction
      between diagnosis and protein (p < 0.01). Analysis stratified according to
      protein showed higher levels in patients with MCI for most proteins, especially
      in patients with MCI-AD. Chromogranin A, secretogranin II, neurexin 3, and
      neuropentraxin 1 showed the largest effect sizes; beta values ranged from 0.53 to
      0.78 for patients with MCI versus control subjects or patients with AD, and from
      0.67 to 0.98 for patients with MCI-AD versus patients with stable MCI. In
      contrast, neurosecretory protein VGF was lower in patients with AD than in
      patients with MCI (beta = -0.93 [SE 0.22]) and control subjects (beta = 0.46 [SE
      0.19]). CONCLUSIONS: Our results suggest that several proteins involved in
      vesicular transport and synaptic stability are elevated in patients with MCI,
      especially in patients with MCI progressing to AD dementia. This may reflect
      early events in the AD pathophysiological cascade. These proteins may be valuable
      as disease stage or prognostic markers in an early symptomatic stage of the
      disease.

PMID- 29370834
TI  - Highly selective inhibition of Bruton's tyrosine kinase attenuates skin and brain
      disease in murine lupus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      that affects different end organs, including skin and brain. We and others have
      previously shown the importance of macrophages in the pathogenesis of cutaneous
      and neuropsychiatric lupus. Additionally, autoantibodies produced by autoreactive
      B cells are thought to play a role in both the skin and central nervous system
      pathologies associated with SLE. METHODS: We used a novel inhibitor of Bruton's
      tyrosine kinase (BTK), BI-BTK-1, to target both macrophage and B cell function in
      the MRL-lpr/lpr murine model of SLE, and examined the effect of treatment on skin
      and brain disease. RESULTS: We found that treatment with BI-BTK-1 significantly
      attenuated the lupus associated cutaneous and neuropsychiatric disease phenotypes
      in MRL/lpr mice. Specifically, BI-BTK-1 treated mice had fewer macroscopic and
      microscopic skin lesions, reduced cutaneous cellular infiltration, and diminished
      inflammatory cytokine expression compared to control mice. BTK inhibition also
      significantly improved cognitive function, and decreased accumulation of T cells,
      B cells, and macrophages within the central nervous system, specifically the
      choroid plexus. CONCLUSIONS: Directed therapies may improve the response rate in
      lupus-driven target organ involvement, and decrease the dangerous side effects
      associated with global immunosuppression. Overall, our results suggest that
      inhibition of BTK may be a promising therapeutic option for cutaneous and
      neuropsychiatric disease associated with SLE.

PMID- 29370836
TI  - Successful eradication of newly acquired MRSA in six of seven patients with
      cystic fibrosis applying a short-term local and systemic antibiotic scheme.
AB  - BACKGROUND: In individuals with cystic fibrosis (CF), colonization with
      methicillin-resistant Staphylococcus aureus (MRSA) was reported to be associated
      with a deterioration of pulmonary disease as reflected by an accelerated decline
      in lung function. Thus, an early eradication of MRSA could be beneficial in these
      patients. Here, we report on an intensified MRSA eradication protocol. METHODS:
      Since 2012 a protocol for the eradication of newly acquired MRSA has been used in
      our CF Clinic, combining oral rifampicin and fusidic acid, inhaled vancomycin,
      nasal mupirocin, local antiseptic treatment and hygienic directives all of which
      are applied for only 7 days during an inpatient hospital stay. RESULTS: Since
      2012 seven patients (3 male, 4 female; age range 4 to 30 years) newly acquired
      MRSA. In 6 of the 7 patients (86%) successful eradication of MRSA was achieved
      upon first treatment using the protocol described above. In one patient a second
      course of treatment was performed which, however, also failed to eliminate the
      colonizing MRSA. CONCLUSIONS: Our protocol led to an eradication rate of 86%. The
      impact of each individual component of the protocol remains to be determined.

PMID- 29370835
TI  - Lifetime utilization of mammography among Maltese women: a cross-sectional
      survey.
AB  - BACKGROUND: The knowledge of Maltese women not attending the Maltese Breast
      Screening Programme (MBSP) for mammography screening is scarce. Previous research
      has identified two distinct groups of non-attendees: those who do not attend
      because a mammogram was taken elsewhere and those who never attended for
      mammography anywhere. It is however unknown which determinants are predictive of
      lifetime attendance 'anywhere' and 'real' non-attendance. The present study
      examines the relationship between ever-using (Lifetime attendees) or never using
      mammography (Lifetime non-attendees) and psychosocial - as well as
      sociodemographic factors, with the aim to identify predictors that can inform
      practice. METHODS: Women's characteristics, knowledge, health beliefs and illness
      perceptions were compared, based on prior data of 404 women, aged 50-60 years at
      the time of their first MBSP invitation. The main variable of interest described
      women's attendance to mammography (LIFETIME ATTENDEES) and no mammography
      (LIFETIME NON-ATTENDEES). Data were analyzed using descriptive statistics, chi
      square tests, Mann Whitney test, Independent Samples t-test, Shapiro Wilk test
      and logistic regression. RESULTS: During their lifetime, 86.1% of Maltese women
      (n = 348) were attendees, while 13.9% (n = 56) were non-attendees. Non-attendees
      were more likely to be women with a lower family income (chi2 = 13.1, p = 0.011),
      widowers (chi2 = 9.0, p = 0.030), non-drivers (chi2 = 7.7, p = 0.006), without a
      breast condition (chi2 = 14.2, p <  0.001), who had no relatives or close friends
      with cancer (chi2 = 8.3, p = 0.016), and who were less encouraged by a physician
      (chi2 = 4.9, p = 0.027), unsure of the screening frequency (chi2 = 28.5, p < 
      0.001), more anxious (p = 0.040) and fearful (p = 0.039). Perceived benefits,
      barriers, cues to action, self-efficacy and emotional representations were the
      most significant variables to describe the differences between lifetime attendees
      and non-attendees. Perceived barriers and cues to action were the strongest
      predictors for lifetime non-attendance (p <  0.05 respectively). CONCLUSIONS: The
      health beliefs of women who have never attended for mammography during their
      lifetime should be targeted, particularly perceived barriers and cues to action.
      Further research should focus on understanding knowledge gaps, attitudinal
      barriers and emotional factors among 'real' non-attendees who require a more
      targeted approach.

PMID- 29370837
TI  - Utilization of health care services among Medicare beneficiaries who visit
      federally qualified health centers.
AB  - BACKGROUND: Previous studies have disagreed on whether patients who receive
      primary care from federally qualified health centers (FQHCs) have different
      utilization patterns than patients who receive care elsewhere. Our objective was
      to compare patterns of healthcare utilization between Medicare beneficiaries who
      received primary care from FQHCs and Medicare beneficiaries who received primary
      care from another source. METHODS: We compared characteristics and ambulatory,
      emergency department (ED), and inpatient utilization during 2013 between 130,637
      Medicare beneficiaries who visited an FQHC for the majority of their primary care
      in 2013 (FQHC users) and a random sample of 1,000,000 Medicare fee-for-service
      (FFS) beneficiaries who did not visit an FQHC (FQHC non-users). We then created a
      propensity-matched sample of 130,569 FQHC users and 130,569 FQHC non-users to
      account for differences in observable patient characteristics between the two
      groups and repeated all comparisons. RESULTS: Before matching, the two samples
      differed in terms of age (42% below age 65 for FQHC users vs. 16% among FQHC non
      users, p < 0.001 for all comparisons), disability (52% vs. 24%), eligibility for
      Medicaid (56% vs. 21%), severe mental health disorders (17% vs. 10%), and
      substance abuse disorders (6% vs. 3%). FQHC users had fewer ambulatory visits to
      primary care or specialist providers (10.0 vs. 12.0 per year), more ED visits
      (1.2 vs. 0.8), and fewer hospitalizations (0.3 vs. 0.4). In the matched sample,
      FQHC users still had slightly lower utilization of ambulatory visits to primary
      care or specialist providers (10.0 vs. 11.2) and slightly higher utilization of
      ED visits (1.2 vs. 1.0), compared to FQHC users. Hospitalization rates between
      the two groups were similar (0.3 vs. 0.3). CONCLUSIONS: In this population of
      Medicare FFS beneficiaries, FQHC users had slightly lower utilization of
      ambulatory visits and slightly higher utilization of ED visits, compared to FQHC
      non-users, after accounting for differences in case mix. This study suggests that
      FQHC care and non-FQHC care are associated with broadly similar levels of
      healthcare utilization among Medicare FFS beneficiaries.

PMID- 29370838
TI  - Extended FTLD pedigree segregating a Belgian GRN-null mutation: neuropathological
      heterogeneity in one family.
AB  - BACKGROUND: In this paper, we describe the clinical and neuropathological
      findings of nine members of the Belgian progranulin gene (GRN) founder family. In
      this family, the loss-of-function mutation IVS1 + 5G > C was identified in 2006.
      In 2007, a clinical description of the mutation carriers was published that
      revealed the clinical heterogeneity among IVS1 + 5G > C carriers. We report our
      comparison of our data with the published clinical and neuropathological
      characteristics of other GRN mutations as well as other frontotemporal lobar
      degeneration (FTLD) syndromes, and we present a review of the literature.
      METHODS: For each case, standardized sampling and staining were performed to
      identify proteinopathies, cerebrovascular disease, and hippocampal sclerosis.
      RESULTS: The neuropathological substrate in the studied family was compatible in
      all cases with transactive response DNA-binding protein (TDP) proteinopathy type
      A, as expected. Additionally, most of the cases presented also with primary age
      related tauopathy (PART) or mild Alzheimer's disease (AD) neuropathological
      changes, and one case had extensive Lewy body pathology. An additional finding
      was the presence of cerebral small vessel changes in every patient in this
      family. CONCLUSIONS: Our data show not only that the IVS1 + 5G > C mutation has
      an exclusive association with FTLD-TDP type A proteinopathy but also that other
      proteinopathies can occur and should be looked for. Because the penetrance rate
      of the clinical phenotype of carriers of GRN mutations is age-dependent, further
      research is required to investigate the role of co-occurring age-related
      pathologies such as AD, PART, and cerebral small vessel disease.

PMID- 29370839
TI  - Efficacy of T-DM1 for leptomeningeal and brain metastases in a HER2 positive
      metastatic breast cancer patient: new directions for systemic therapy - a case
      report and literature review.
AB  - BACKGROUND: Herein, we report a complete response after whole brain radiotherapy
      (WBRT) and concomitant T-DM1 in a patient with HER2-positive metastatic breast
      cancer (MBC) and extensive brain and leptomeningeal involvement. CASE
      PRESENTATION: A 46 years old Caucasian woman with HER2-positive MBC and no
      baseline CNS involvement, started in August 2015 1st line therapy with Pertuzumab
      Trastuzumab-Docetaxel, with partial response. However, in April 2016 the patient
      eventually progressed with emergence of brain and leptomeningeal metastases.
      Hence, she started in May 2016 2nd line therapy with T-DM1 and concomitant WBRT,
      with complete response (CR) after 3 courses of therapy, with complete resolution
      of neurological symptoms and no relevant toxicities. The CR is lasting over 13
      months and the patient is out of corticosteroid use. CONCLUSIONS: To the best of
      our knowledge, this is the first case reporting interesting antitumor activity of
      T-DM1 and concomitant WBRT in both brain and leptomeningeal metastases, with a
      favorable safety profile and prolonged extracranial disease control. Further
      prospective studies should confirm these findings.

PMID- 29370840
TI  - Identification of compound heterozygous variants in the noncoding RNU4ATAC gene
      in a Chinese family with two successive foetuses with severe microcephaly.
AB  - BACKGROUND: Whole-exome sequencing (WES) over the last few years has been
      increasingly employed for clinical diagnosis. However, one caveat with its use is
      that it inevitably fails to detect disease-causative variants that occur within
      noncoding RNA genes. Our experience in identifying pathogenic variants in the
      noncoding RNU4ATAC gene, in a Chinese family where two successive foetuses had
      been affected by severe microcephaly, is a case in point. These foetuses
      exhibited remarkably similar phenotypes in terms of their microcephaly and brain
      abnormalities; however, the paucity of other characteristic phenotypic features
      had made a precise diagnosis impossible. Given that no external causative factors
      had been reported/identified during the pregnancies, we sought a genetic cause
      for the phenotype in the proband, the second affected foetus. RESULTS: A search
      for chromosomal abnormalities and pathogenic copy number variants proved
      negative. WES was also negative. These initial failures prompted us to consider
      the potential role of RNU4ATAC, a noncoding gene implicated in microcephalic
      osteodysplastic primordial dwarfism type-1 (MOPD1), a severe autosomal recessive
      disease characterised by dwarfism, severe microcephaly and neurological
      abnormalities. Subsequent targeted sequencing of RNU4ATAC resulted in the
      identification of compound heterozygous variants, one being the most frequently
      reported MOPD1-causative mutation (51G>A), whereas the other was a novel 29T>A
      variant. Four distinct lines of evidence (allele frequency in normal populations,
      evolutionary conservation of the affected nucleotide, occurrence within a known
      mutational hotspot for MOPD1-causative variants and predicted effect on RNA
      secondary structure) allowed us to conclude that 29T>A is a new causative variant
      for MOPD1. CONCLUSIONS: Our findings highlight the limitations of WES in failing
      to detect variants within noncoding RNA genes and provide support for a role for
      whole-genome sequencing as a first-tier genetic test in paediatric medicine.
      Additionally, the identification of a novel RNU4ATAC variant within the
      mutational hotspot for MOPD1-causative variants further strengthens the critical
      role of the 5' stem-loop structure of U4atac in health and disease. Finally, this
      analysis enabled us to provide prenatal diagnosis and genetic counselling for the
      mother's third pregnancy, the first report of its kind in the context of
      inherited RNU4ATAC variants.

PMID- 29370842
TI  - General service and child immunization-specific readiness assessment of
      healthcare facilities in two selected divisions in Bangladesh.
AB  - BACKGROUND: Service readiness of health facilities is an integral part of
      providing comprehensive quality healthcare to the community. Comprehensive
      assessment of general and service-specific (i.e. child immunization) readiness
      will help to identify the bottlenecks in healthcare service delivery and gaps in
      equitable service provision. Assessing healthcare facilities readiness also helps
      in optimal policymaking and resource allocation. METHODS: A health facility
      survey was conducted between March 2015 and December 2015 in two purposively
      selected divisions in Bangladesh; i.e. Rajshahi division (high performing) and
      Sylhet division (low performing). A total of 123 health facilities were randomly
      selected from different levels of service, both public and private, with
      variation in sizes and patient loads from the list of facilities. Data on various
      aspects of healthcare facility were collected by interviewing key personnel.
      General service and child immunization specific service readiness were assessed
      using the Service Availability and Readiness Assessment (SARA) manual developed
      by World Health Organization (WHO). The analyses were stratified by division and
      level of healthcare facilities. RESULTS: The general service readiness index for
      pharmacies, community clinics, primary care facilities and higher care facilities
      were 40.6%, 60.5%, 59.8% and 69.5%, respectively in Rajshahi division and 44.3%,
      57.8%, 57.5% and 73.4%, respectively in Sylhet division. Facilities at all levels
      had the highest scores for basic equipment (ranged between 51.7% and 93.7%) and
      the lowest scores for diagnostic capacity (ranged between 0.0% and 53.7%). Though
      facilities with vaccine storage capacity had very high levels of service
      readiness for child immunization, facilities without vaccine storage capacity
      lacked availability of many tracer items. Regarding readiness for newly
      introduced pneumococcal conjugate vaccine (PCV) and inactivated polio vaccine
      (IPV), most of the surveyed facilities reported lack of sufficient funding and
      resources (antigen) for training programs. CONCLUSIONS: Our study suggested that
      health facilities suffered from lack of readiness in various aspects, most
      notably in diagnostic capacity. Conversely, with very few challenges, nearly all
      the health facilities designated to provide immunization services were ready to
      deliver routine childhood immunization services as well as newly introduced PCV
      and IPV.

PMID- 29370841
TI  - Expression of functional inhibitory neurotransmitter transporters GlyT1, GAT-1,
      and GAT-3 by astrocytes of inferior colliculus and hippocampus.
AB  - Neuronal inhibition is mediated by glycine and/or GABA. Inferior colliculus (IC)
      neurons receive glycinergic and GABAergic inputs, whereas inhibition in
      hippocampus (HC) predominantly relies on GABA. Astrocytes heterogeneously express
      neurotransmitter transporters and are expected to adapt to the local requirements
      regarding neurotransmitter homeostasis. Here we analyzed the expression of
      inhibitory neurotransmitter transporters in IC and HC astrocytes using whole-cell
      patch-clamp and single-cell reverse transcription-PCR. We show that most
      astrocytes in both regions expressed functional glycine transporters (GlyTs).
      Activation of these transporters resulted in an inward current (IGly) that was
      sensitive to the competitive GlyT1 agonist sarcosine. Astrocytes exhibited
      transcripts for GlyT1 but not for GlyT2. Glycine did not alter the membrane
      resistance (RM) arguing for the absence of functional glycine receptors (GlyRs).
      Thus, IGly was mainly mediated by GlyT1. Similarly, we found expression of
      functional GABA transporters (GATs) in all IC astrocytes and about half of the HC
      astrocytes. These transporters mediated an inward current (IGABA) that was
      sensitive to the competitive GAT-1 and GAT-3 antagonists NO711 and SNAP5114,
      respectively. Accordingly, transcripts for GAT-1 and GAT-3 were found but not for
      GAT-2 and BGT-1. Only in hippocampal astrocytes, GABA transiently reduced RM
      demonstrating the presence of GABAA receptors (GABAARs). However, IGABA was
      mainly not contaminated by GABAAR-mediated currents as RM changes vanished
      shortly after GABA application. In both regions, IGABA was stronger than IGly.
      Furthermore, in HC the IGABA/IGly ratio was larger compared to IC. Taken
      together, our results demonstrate that astrocytes are heterogeneous across and
      within distinct brain areas. Furthermore, we could show that the capacity for
      glycine and GABA uptake varies between both brain regions.

PMID- 29370843
TI  - Validation of the 24-item recovery assessment scale-revised (RAS-R) in the
      Norwegian language and context: a multi-centre study.
AB  - BACKGROUND: The Recovery Assessment Scale-revised (RAS-R) is a self-report
      instrument measuring mental health recovery. The purpose of the present study was
      to translate and adapt the RAS-R into the Norwegian language and to investigate
      its psychometric properties in terms of factor structure, convergent and
      discriminant validity and reliability in the Norwegian context. METHODS: The
      present study is a cross-sectional multi-centre study. After a pilot test, the
      Norwegian version of the RAS-R was distributed to 231 service users in mental
      health specialist and community services. The factor structure of the instrument
      was investigated by a confirmatory factor analysis (CFA), and internal
      consistency was assessed by Cronbach's alpha. RESULTS: The RAS-R was found to be
      acceptable and feasible for service users. The original five-factor structure was
      confirmed. All model fit indices, including the standardised root mean square
      residual (SRMR), which is independent of the chi2-test, met the criteria for an
      acceptable model fit. Internal consistencies within sub-scales as measured by
      Cronbach's alpha ranged from 0.65 to 0.85. Cronbach's alpha for the total scale
      was 0.90. As expected, some redundancy between factors existed (in particular
      among the factors Personal confidence and hope, Goal and success orientation and
      Not dominated by symptoms). CONCLUSIONS: The Norwegian RAS-R showed acceptable
      psychometric properties in terms of convergent validity and reliability, and fit
      indices from the CFA confirmed the original factor structure. We recommend the
      Norwegian RAS-R as a tool in service users' and health professionals'
      collaborative work towards the service users' recovery goals and as an outcome
      measure in larger evaluations.

PMID- 29370844
TI  - Efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine and artemether
      lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in
      Maradi, Niger.
AB  - BACKGROUND: Malaria endemic countries need to assess efficacy of anti-malarial
      treatments on a regular basis. Moreover, resistance to artemisinin that is
      established across mainland South-East Asia represents today a major threat to
      global health. Monitoring the efficacy of artemisinin-based combination therapies
      is of paramount importance to detect as early as possible the emergence of
      resistance in African countries that toll the highest burden of malaria morbidity
      and mortality. METHODS: A WHO standard protocol was used to assess efficacy of
      the combinations artesunate-amodiaquine (AS-AQ Winthrop(r)), dihydroartemisinin
      piperaquine (DHA-PPQ, Eurartesim(r)) and artemether-lumefantrine (AM-LM,
      Coartem(r)) taken under supervision and respecting pharmaceutical
      recommendations. The study enrolled for each treatment arm 212 children aged 6-59
      months living in Maradi (Niger) and suffering with uncomplicated falciparum
      malaria. The Kaplan-Meier 42-day PCR-adjusted cure rate was the primary outcome.
      A standardized parasite clearance estimator was used to assess delayed parasite
      clearance as surrogate maker of suspected artemisinin resistance. RESULTS: No
      early treatment failures were found in any of the study treatment arms. The day
      42 PCR-adjusted cure rate estimates were 99.5, 98.4 and 99.0% in the AS-AQ, DHA
      PPQ and AM-LM arms, respectively. The reinfection rate (expressed also as Kaplan
      Meier estimates) was higher in the AM-LM arm (32.4%) than in the AS-AQ (13.8%)
      and the DHA-PPQ arm (24.9%). The parasite clearance rate constant was 0.27, 0.26
      and 0.25 per hour for AS-AQ, DHA-PPQ and AM-LM, respectively. CONCLUSIONS: All
      the three treatments evaluated largely meet WHO criteria (at least 95% efficacy).
      AS-AQ and AL-LM may continue to be used and DHA-PPQ may be also recommended as
      first-line treatment for uncomplicated falciparum malaria in Maradi. The parasite
      clearance rate were consistent with reference values indicating no suspected
      artemisinin resistance. Nevertheless, the monitoring of anti-malarial drug
      efficacy should continue. Trial registration details Registry number at
      ClinicalTrial.gov: NCT01755559.

PMID- 29370846
TI  - Exacerbations and healthcare resource utilization among COPD patients in a
      Swedish registry-based nation-wide study.
AB  - BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are an
      important measure of disease severity in terms of impaired disease progression,
      increased recovery time, healthcare resource utilization, overall morbidity and
      mortality. We aimed to quantify exacerbation and healthcare resource utilization
      rates among COPD patients in Sweden with respect to baseline treatments,
      exacerbation history, and comorbidities. METHODS: Patients with a COPD or chronic
      bronchitis (CB) diagnosis in secondary care at age of >=40 years on 1.7.2009 were
      identified and followed until 1.7.2010 or death. Severe exacerbations were
      defined as hospitalizations due to respiratory disease, and healthcare resource
      utilization was measured by all-cause hospitalizations and secondary care visits.
      Poisson regression was used adjusting for age, gender, time since COPD/CB
      diagnosis, and Charlson comorbidity index. RESULTS: In 88,548 patients (54%
      females, mean age 72 years), previous respiratory hospitalizations and current
      high use of COPD medication (double or triple therapy) predicted an 8.3-fold
      increase in severe exacerbation rates and 1.8-fold increase in healthcare
      resource utilization rates in the following year, compared to patients without
      combination treatment and/or history of severe exacerbations. CONCLUSIONS:
      COPD/CB patients with history of severe exacerbations and high use of COPD
      medication experienced a significantly increased rate of severe exacerbations and
      healthcare resource utilization during the one-year follow-up.

PMID- 29370845
TI  - Quality improvement initiatives for hospitalised small and sick newborns in low-
      and middle-income countries: a systematic review.
AB  - BACKGROUND: An estimated 2.6 million newborns died in 2016; over 98.5% of deaths
      occurred in low- and middle-income countries (LMICs). Neonates born preterm and
      small for gestational age are particularly at risk given the high incidence of
      infectious complications, cardiopulmonary, and neurodevelopmental disorders in
      this group. Quality improvement (QI) initiatives can reduce the burden of
      mortality and morbidity for hospitalised newborns in these settings. We undertook
      a systematic review to synthesise evidence from LMICs on QI approaches used,
      outcome measures employed to estimate effects, and the nature of implementation
      challenges. METHODS: We searched Medline, EMBASE, WHO Global Health Library,
      Cochrane Library, WHO ICTRP, and ClinicalTrials.gov and scanned the references of
      identified studies and systematic reviews. Searches covered January 2000 until
      April 2017. Search terms were "quality improvement", "newborns", "hospitalised",
      and their derivatives. Studies were excluded if they took place in high-income
      countries, did not include QI interventions, or did not include small and sick
      hospitalised newborns. Cochrane Risk of Bias tools were used to quality appraise
      the studies. RESULTS: From 8110 results, 28 studies were included, covering 23
      LMICs and 65,642 participants. Most interventions were meso level (district and
      clinic level); fewer were micro (patient-provider level) or macro (above district
      level). In-service training was the most common intervention subtype; service
      organisation and distribution of referencing materials were also frequently
      identified. The most commonly assessed outcome was mortality, followed by length
      of admission, sepsis rates, and infection rates. Key barriers to implementation
      of quality improvement initiatives included overburdened staff and lack of
      sufficient equipment. CONCLUSIONS: The frequency of meso level, single centre,
      and educational interventions suggests that these interventions may be easier for
      programme planners to implement. The success of some interventions in reducing
      morbidity and mortality rates suggests that QI approaches have a high potential
      for benefit to newborns. Going forward, there are opportunities to strengthen the
      focus of QI initiatives and to develop improved, larger-scale, collaborative
      research into implementation of quality improvement initiatives for this high
      risk group. TRIAL REGISTRATION: PROSPERO CRD42017055459 .

PMID- 29370847
TI  - Rethinking Disability.
AB  - Disability as a health outcome deserves more attention than it has so far
      received. With people living longer and the epidemiological transition from
      infectious to noncommunicable diseases as the major cause of health burden, we
      need to focus attention on disability - the non-fatal impact of heath conditions 
      over and above our concern for causes of mortality.With the first Global Burden
      of Disease study, WHO provided a metric that enabled the comparison of the impact
      of diseases, drawing on a model of disability that focused on decrements of
      health. This model has since been elaborated in the International Classification
      of Functioning, Disability and Health as being either a feature of the individual
      or arising out of the interaction between the individual's health condition and
      contextual factors. The basis of WHO's ongoing work is a set of principles: that
      disability is a universal human experience; that disability is not determined
      solely by the underlying health condition or predicated merely on the presence of
      specific health conditions; and finally, that disability lies on a continuum from
      no to complete disability. To determine whether interventions at individual or
      population levels are effective, an approach to disability measurement that
      allows for an appropriate and fair comparison across health conditions is needed.
      WHO has designed the Model Disability Survey (MDS) to collect information
      relevant to understand the lived experience of disability, including the person's
      capacity to perform tasks actions in daily life, their actual performance, the
      barriers and facilitators in the environment they experience, and their health
      conditions. As disability gains prominence within the development agenda in the
      United Nations Sustainable Development Goals, and the implementation of the
      United Nations Convention on the Rights of Persons with Disabilities, the MDS
      will provide the data to monitor the progress of countries on meeting their
      obligations.The lesson learned from WHO's activities is that disability is a
      universal human experience, in the sense that everyone can be placed on a
      continuum of functioning and either currently experiences or is vulnerable to
      experiencing disability over the course of their lives. This understanding of
      disability is the key to mainstreaming disability within the public discourse.

PMID- 29370848
TI  - Computed tomography and magnetic resonance imaging evaluation of pelvic lymph
      node metastasis in bladder cancer.
AB  - BACKGROUND: Accurate evaluation of lymph node metastasis in bladder cancer (BCa)
      is important for disease staging, treatment selection, and prognosis prediction.
      In this study, we aimed to evaluate the diagnostic accuracy of computed
      tomography (CT) and magnetic resonance imaging (MRI) for metastatic lymph nodes
      in BCa and establish criteria of imaging diagnosis. METHODS: We retrospectively
      assessed the imaging characteristics of 191 BCa patients who underwent radical
      cystectomy. The data regarding size, shape, density, and diffusion of the lymph
      nodes on CT and/or MRI were obtained and analyzed using Kruskal-Wallis test and
      chi2 test. The optimal cutoff value for the size of metastatic node was
      determined using the receiver operating characteristic (ROC) curve analysis.
      RESULTS: A total of 184 out of 3317 resected lymph nodes were diagnosed as
      metastatic lymph nodes. Among 82 imaging-detectable lymph nodes, 51 were
      confirmed to be positive for metastasis. The detection rate of metastatic nodes
      increased along with more advanced tumor stage (P < 0.001). Once the ratio of
      short- to long-axis diameter <= 0.4 or fatty hilum was observed in lymph nodes on
      imaging, it indicated non-metastases. Besides, lymph nodes with spiculate or
      obscure margin or necrosis indicated metastases. Furthermore, the short diameter
      of 6.8 mm was the optimal threshold to diagnose metastatic lymph node, with the
      area under ROC curve of 0.815. CONCLUSIONS: The probability of metastatic nodes
      significantly increased with more advanced T stages. Once lymph nodes are
      detected on imaging, the characteristic signs should be paid attention to. The
      short diameter > 6.8 mm may indicate metastatic lymph nodes in BCa.

PMID- 29370849
TI  - Predictors of one-year mortality after hospitalization for an exacerbation of
      COPD.
AB  - BACKGROUND: Hospitalization for a severe exacerbation of COPD (eCOPD) is an
      important event in the natural history of COPD. Identifying factors related to
      mortality 1 year after hospitalization could help determine interventions to
      reduce mortality. METHODS: In a prospective, observational, multicentre study, we
      evaluated data from two cohorts: the Spanish audit of hospital COPD exacerbation
      care (our derivation sample) and the Spanish cohort of the European audit of COPD
      exacerbation care (our validation sample). The endpoint was all-cause mortality.
      Mortality was determined by local research managers of the participating
      hospitals and matched the official national index records in Spain. RESULTS: In
      the multivariate analysis, factors independently related to an increase in
      mortality were older age, cardio-cerebro-vascular and/or dementia comorbidities,
      PaCO2 > 55 mmHg measured at emergency department arrival, hospitalizations for
      COPD exacerbations in the previous year, and hospital characteristics. The area
      under the receiver-operating curve for this model was 0.75 in the derivation
      cohort and 0.76 in the validation cohort. CONCLUSION: One-year mortality
      following the index hospitalization for an exacerbation of COPD was related to
      clinical characteristics of the patient and of the index event, previous events
      of similar severity, and characteristics of the hospital where the patient was
      treated.

PMID- 29370850
TI  - Reporting of pain by people with chronic obstructive pulmonary disease (COPD):
      comparative results from the HUNT3 population-based survey.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often associated with
      chronic pain, but pain in COPD remains poorly understood, particularly in
      comparison to pain in other groups. We compared the pain reported by people with
      COPD with that reported by arthritis, heart disease, diabetes, and those not
      reporting any disease, while adjusting for the effects of selected
      sociodemographic and lifestyle factors, comorbidities, anxiety, and depression.
      METHODS: Using cross-sectional data from a population-based health survey in
      Norway (HUNT3; n = 50,807), we included participants with COPD (n = 1199),
      participants without COPD, but with arthritis (n = 8582), heart disease (n =
      4109), or diabetes (n = 1254), and participants without any disease (n = 18,811).
      Logistic and linear regression analyses were performed to estimate the
      probability of reporting chronic pain and the level of pain intensity in the
      different groups adjusting for other relevant factors. RESULTS: Approximately
      half (51.8%) of people with COPD reported chronic pain, which was a significantly
      higher rate than in the diabetes and non-disease groups, and similar to the heart
      disease group. People with arthritis had a chronic pain rate of 75.4%, which was
      higher than all other groups, including COPD. Analyses of pain intensity yielded
      similar findings, with the COPD group having higher pain intensity than the
      diabetes and non-disease groups, similar pain intensity as the heart disease
      group, and less pain intensity than the arthritis group. The likelihood of
      chronic pain and the intensity of pain were generally higher among women, people
      employed in occupations with low educational requirements, smokers, and those
      with comorbidity. Chronic pain rates and pain intensity increased with age and
      higher anxiety and depression scores, and were inversely related to physical
      activity. CONCLUSIONS: People with COPD are at increased risk for chronic pain
      and higher pain intensity, second only to those with arthritis among the disease
      groups included in this study. The findings indicate a close relationship between
      pain and anxiety and depression. The relationships between pain and socioeconomic
      and lifestyle factors (e.g., smoking and exercise) suggest the need for efforts
      at the societal level to reduce inequality in health.

PMID- 29370851
TI  - Subclinical hypothyroidism would not lead to female sexual dysfunction in Chinese
      women.
AB  - BACKGROUND: There is dearth of research about female sexual dysfunction (FSD),
      especially in China, because of conservative beliefs. Previous studies indicated
      the relationship between subclinical hypothyroidism and anxiety and depression.
      However, there is dearth of research regarding the relationship between
      subclinical hypothyroidism and FSD in Chinses women. METHOD: A hospital-based
      research was conducted. Female sexual function was measured by CVFSFI which
      includes 19 items. Participants were identified as FSD if CVFSFI <= 23.45.
      Logistics analysis was used to determine risk factor of FSD. All of them finished
      CVFSFI, Beck Depression Inventory (BDI) self-reporting questionnaires and had
      thyroid hormone tests. Based on presence and absence of subclinical
      hypothyroidism, participants were divided into two groups. Risk factors of FSD
      were identified. RESULT: One thousand one hundred nineteen participants with
      CVFSFI score 25.8 +/- 3.9 were enrolled in final analysis. Incidence of
      subclinical hypothyroidism and FSD in Chinese women was 15.0% and 26.5%
      respectively. There were no significant difference between subclinical
      hypothyroidism and control group in FSFI score and prevalence of FSD. Age,
      Depression (medium risk) was identified as risk factors for nearly all types of
      FSD, and Income (ranges from 40,000 to 100,000 RMB/year) as protective factor.
      Subclinical hypothyroidism had no significant relationship with FSD. CONCLUSION:
      Subclinical hypothyroidism is not the risk factor for FSD in urban women of
      China.

PMID- 29370852
TI  - Multiple mini interview (MMI) for general practice training selection in
      Australia: interviewers' motivation.
AB  - BACKGROUND: Multiple Mini Interviews (MMIs) are being used by a growing number of
      postgraduate training programs and medical schools as their interview process for
      selection entry. The Australian General Practice and Training (AGPT) used a
      National Assessment Centre (NAC) approach to selection into General Practice (GP)
      Training, which include MMIs. Interviewing is a resource intensive process, and
      implementation of the MMI requires a large number of interviewers, with a number
      of candidates being interviewed simultaneously. In 2015, 308 interviewers
      participated in the MMI process - a decrease from 340 interviewers in 2014, and
      310 in 2013. At the same time, the number of applicants has steadily increased,
      with 1930 applications received in 2013; 2254 in 2014; and 2360 in 2015. This has
      raised concerns regarding the increasing recruitment needs, and the need to
      retain interviewers for subsequent years of MMIs. In order to investigate
      interviewers' reasons for participating in MMIs, we utilised self-determination
      theory (SDT) to consider interviewers' motivation to take part in MMIs at
      national selection centres. METHODS: In 2015, 308 interviewers were recruited
      from 17 Regional Training Providers (RTPs) to participate in the MMI process at
      one of 15 NACs. For this study, a convenience sample of NAC sites was used. Forty
      interviewers were interviewed (n = 40; 40/308 = 13%) from five NACs. Framework
      analysis was used to code and categorise data into themes. RESULTS: Interviewers'
      motivation to take part as interviewers were largely related to their sense of
      duty, their desire to contribute their expertise to the process, and their desire
      to have input into selection of GP Registrars; a sense of duty to their
      profession; and an opportunity to meet with colleagues and future trainees.
      Interviewers also highlighted factors hindering motivation, which sometimes
      included the large number of candidates seen in one day. CONCLUSION:
      Interviewers' motivation for contributing to the MMIs was largely related to
      their desire to contribute to their profession, and ultimately improve future
      patient care. Interviewers recognised the importance of interviewing, and felt
      their individual roles made a crucial contribution to the profession of general
      practice. Good administration and leadership at each NAC is needed. By gaining an
      understanding of interviewers' motivation, and enhancing this, engagement and
      retention of interviewers may be increased.

PMID- 29370853
TI  - Treatment of cervical cancer in HIV-seropositive women from developing countries:
      a protocol for a systematic review.
AB  - BACKGROUND: Cervical cancer has become the most common cancer affecting women in
      Africa. Significantly, 85% of these annual deaths occur in the developing world,
      with the majority being middle-aged women. Research has shown that in sub-Saharan
      Africa, cervical cancer trends are on the rise in the past two decades because of
      HIV and this has resulted in an increase in cervical cancer cases among young
      women. However, little or no information exists that has shown that any of the
      available treatment methods are more effective than others when it comes to
      treating cervical cancer in HIV-seropositive women. The aim of this protocol is
      to offer a plan on how to systematically review cervical cancer treatment methods
      available for HIV-seropositive women in developing countries. METHODS/DESIGN: The
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols
      (PRISMA-P) statement was used to develop the protocol for the systematic review
      which will be reported in accordance with the PRISMA guidelines. A number of
      databases, Embase, MEDLINE, PubMed, CINAHL and Cochrane Library, will be searched
      for relevant studies, and citation and reference list tracking will be used to
      search for additional studies. Prospective and retrospective cohort studies, case
      control, randomised controlled trials and cross-sectional studies that were
      carried out in and for the developing world will be eligible for inclusion. Peer
      reviewed studies and grey literature examining cervical cancer treatment
      modalities in HIV-seropositive women will be included. Descriptive statistics and
      tables will be used to summarise results, and meta-analysis will be used where
      appropriate. DISCUSSION: The review findings will provide the current picture of
      the existing treatment methods being used to treat cervical cancer in HIV
      seropositive women in developing countries. The findings might be used for the
      establishment of evidence-based guidelines for treatment of cervical cancer in
      seropositive women as well as prompt policy-makers and governments to decide and
      support future research in a way to find a lasting solution. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42017054676
      https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=54676.

PMID- 29370854
TI  - Dual function of active constituents from bark of Ficus racemosa L in wound
      healing.
AB  - BACKGROUND: Different parts including the latex of Ficus racemosa L. has been
      used as a medicine for wound healing in the Ayurveda and in the indigenous system
      of medicine in Sri Lanka. This plant has been evaluated for its wound healing
      potential using animal models. The aim of this study was to obtain an insight
      into the wound healing process and identify the potential wound healing active
      substance/s present in F. racemosa L. bark using scratch wound assay (SWA) as the
      in-vitro assay method. METHOD: Stem bark extracts of F. racemosa were evaluated
      using scratch wound assay (SWA) on Baby Hamster Kidney (BHK 21) and Madin-Darby
      Canine Kidney (MDCK) cell lines and Kirby Bauer disc diffusion assay on common
      bacteria and fungi for cell migration enhancing ability and antimicrobial
      activity respectively. Dichloromethane and hexanes extracts which showed cell
      migration enhancement activity on SWA were subjected to bioactivity directed
      fractionation using column chromatography followed by preparative thin layer
      chromatography to identify the compounds responsible for the cell migration
      enhancement activity. RESULTS: Dichloromethane and hexanes extracts showed cell
      migration enhancement activity on both cell lines, while EtOAc and MeOH extracts
      showed antibacterial activity against Staphylococcus and Bacillus species and
      antifungal activity against Saccharomyces spp. and Candida albicans. Lupeol (1)
      and beta-sitosterol (2) were isolated as the potential wound healing active
      compounds which exhibited significant cell migration enhancement activity on BHK
      21 and MDCK cell lines (> 80%) in par with the positive control, asiaticoside at
      a concentration of 25 MUM. The optimum concentration of each compound required
      for the maximum wound healing has been determined as 30 MUM and 35 MUM for 1 and
      2 respectively on both cell lines. It is also established that lupeol acetate (3)
      isolated from the hexanes extract act as a pro-drug by undergoing hydrolysis into
      lupeol in the vicinity of cells. CONCLUSION: Different chemical constituents
      present in stem bark of Ficus racemosa L show enhancement of cell migration
      (which corresponds to the cell proliferation) as well as antimicrobial activity.
      This dual action of F. racemosa stem bark provides scientific support for its
      traditional use in wound healing.

PMID- 29370856
TI  - Ultrasonography and magnetic resonance imaging changes in patients with
      polymyalgia rheumatica treated by tocilizumab.
AB  - BACKGROUND: This study assessed inflammatory changes using ultrasound (US) and
      magnetic resonance imaging (MRI) in patients taking tocilizumab for polymyalgia
      rheumatica (PMR). METHODS: Eighteen patients were included in the prospective
      open-label TENOR study and received three tocilizumab infusions, without
      corticosteroids. B-mode and power Doppler US and MRI (T1 and T2-short time
      inversion recuperation weighted sequences) of the hips and shoulders were
      performed at weeks 0, 2, and 12. Subacromial, trochanteric, and iliopsoas
      bursitis and intraarticular glenohumeral and coxofemoral effusions/synovitis were
      scored from 0 to 3. Changes over time and US-MRI correlations were evaluated.
      RESULTS: At baseline, the proportions of shoulders and hips with bursitis were 93
      and 100% by MRI and 61 and 13% by US; and the corresponding proportions for
      intraarticular effusions/synovitis were 100 and 100% by MRI and 57 and 53% by US.
      Imaging findings did not improve during the first two treatment weeks. From
      baseline to week 12, bursitis improved significantly at all four joints by MRI (P
      = 0.005) and US (P = 0.029) and intraarticular effusions/synovitis by US only (P
      = 0.001). The proportion of abnormalities that improved by week 12 was 42% by MRI
      and 37% by US. MRI detected bursitis in a larger proportion of hips (73% versus
      13%) and US in a larger proportion of shoulders (57% versus 28%), whereas no
      difference was found for intraarticular effusions/synovitis. At baseline,
      agreement between US and MRI findings was poor. CONCLUSIONS: US and MRI showed
      significant improvements in inflammatory lesions during tocilizumab treatment of
      PMR.

PMID- 29370855
TI  - Of dogs and hookworms: man's best friend and his parasites as a model for
      translational biomedical research.
AB  - We present evidence that the dog hookworm (Ancylostoma caninum) is underutilised
      in the study of host-parasite interactions, particularly as a proxy for the human
      hookworm relationship. The inability to passage hookworms through all life stages
      in vitro means that adult stage hookworms have to be harvested from the gut of
      their definitive hosts for ex vivo research. This makes study of the human
      hookworm interface difficult for technical and ethical reasons. The historical
      association of humans, dogs and hookworms presents a unique triad of positive
      evolutionary pressure to drive the A. caninum-canine interaction to reflect that
      of the human-hookworm relationship. Here we discuss A. caninum as a proxy for
      human hookworm infection and situate this hookworm model within the current
      research agenda, including the various 'omics' applications and the search for
      next generation biologics to treat a plethora of human diseases. Historically,
      the dog hookworm has been well described on a physiological and biochemical
      level, with an increasing understanding of its role as a human zoonosis. With its
      similarity to human hookworm, the recent publications of hookworm genomes and
      other omics databases, as well as the ready availability of these parasites for
      ex vivo culture, the dog hookworm presents itself as a valuable tool for
      discovery and translational research.

PMID- 29370857
TI  - Environmental resistance development to influenza antivirals: a case exemplifying
      the need for a multidisciplinary One Health approach including physicians.
AB  - A multidisciplinary approach is a prerequisite for One Health. Physicians are
      important players in the One Health team, yet they are often hard to convince of
      the benefits of the One Health approach. Here, the case for multidisciplinarity
      including physicians is made using the example of environmental resistance
      development to influenza antivirals. Neuraminidase inhibitors are the major class
      of anti-influenza pharmaceuticals, and extensively stockpiled globally as a
      cornerstone of pandemic preparedness, especially important in the first phase
      before vaccines can be mass-produced. The active metabolite of oseltamivir that
      is excreted from treated patients degrades poorly in conventional sewage
      treatment processes and has been found in river waters. Dabbling ducks constitute
      the natural influenza A virus reservoir and often reside near sewage treatment
      plant outlets, where they may be exposed to neuraminidase inhibitor residues. In
      vivo experiments using influenza-infected Mallards exposed to neuraminidase
      inhibitors present in their water have shown resistance development and
      persistence, demonstrating that resistance may be induced and become established
      in the influenza strains circulating in natural hosts. Neuraminidase inhibitor
      resistance genes may become part of a human-adapted influenza virus with pandemic
      potential through reassortment or direct transmission. A pandemic caused by a
      neuraminidase inhibitor-resistant influenza virus is a serious threat as the
      first line defense in pandemic preparedness would be disarmed. To assess the risk
      for environmental influenza resistance development, a broad multidisciplinary
      team containing chemists, social scientists, veterinarians, biologists,
      ecologists, virologists, epidemiologists, and physicians is needed. Information
      about One Health early in high school and undergraduate training, an active
      participation of One Health-engaged physicians in the debate, and more One Health
      adapted funding and publication possibilities are suggested to increase the
      possibility to engage physicians.

PMID- 29370859
TI  - Further analysis of the relationship between atmospheric lead emissions and
      aggressive crime: an ecological study.

PMID- 29370860
TI  - Colonoscopy procedure simulation: virtual reality training based on a real time
      computational approach.
AB  - BACKGROUND: Colonoscopy plays an important role in the clinical screening and
      management of colorectal cancer. The traditional 'see one, do one, teach one'
      training style for such invasive procedure is resource intensive and ineffective.
      Given that colonoscopy is difficult, and time-consuming to master, the use of
      virtual reality simulators to train gastroenterologists in colonoscopy operations
      offers a promising alternative. METHODS: In this paper, a realistic and real-time
      interactive simulator for training colonoscopy procedure is presented, which can
      even include polypectomy simulation. Our approach models the colonoscopy as thick
      flexible elastic rods with different resolutions which are dynamically adaptive
      to the curvature of the colon. More material characteristics of this deformable
      material are integrated into our discrete model to realistically simulate the
      behavior of the colonoscope. CONCLUSION: We present a simulator for training
      colonoscopy procedure. In addition, we propose a set of key aspects of our
      simulator that give fast, high fidelity feedback to trainees. We also conducted
      an initial validation of this colonoscopic simulator to determine its clinical
      utility and efficacy.

PMID- 29370861
TI  - Toolbox for Research, or how to facilitate a central data management in small
      scale research projects.
AB  - BACKGROUND: In most research projects budget, staff and IT infrastructures are
      limiting resources. Especially for small-scale registries and cohort studies
      professional IT support and commercial electronic data capture systems are too
      expensive. Consequently, these projects use simple local approaches (e.g. Excel)
      for data capture instead of a central data management including web-based data
      capture and proper research databases. This leads to manual processes to merge,
      analyze and, if possible, pseudonymize research data of different study sites.
      RESULTS: To support multi-site data capture, storage and analyses in small-scall
      research projects, corresponding requirements were analyzed within the MOSAIC
      project. Based on the identified requirements, the Toolbox for Research was
      developed as a flexible software solution for various research scenarios.
      Additionally, the Toolbox facilitates data integration of research data as well
      as metadata by performing necessary procedures automatically. Also, Toolbox
      modules allow the integration of device data. Moreover, separation of personally
      identifiable information and medical data by using only pseudonyms for storing
      medical data ensures the compliance to data protection regulations. This
      pseudonymized data can then be exported in SPSS format in order to enable
      scientists to prepare reports and analyses. CONCLUSIONS: The Toolbox for Research
      was successfully piloted in the German Burn Registry in 2016 facilitating the
      documentation of 4350 burn cases at 54 study sites. The Toolbox for Research can
      be downloaded free of charge from the project website and automatically installed
      due to the use of Docker technology.

PMID- 29370858
TI  - Chronic diseases, inflammation, and spices: how are they linked?
AB  - Extensive research within the last several decades has revealed that the major
      risk factors for most chronic diseases are infections, obesity, alcohol, tobacco,
      radiation, environmental pollutants, and diet. It is now well established that
      these factors induce chronic diseases through induction of inflammation. However,
      inflammation could be either acute or chronic. Acute inflammation persists for a
      short duration and is the host defense against infections and allergens, whereas
      the chronic inflammation persists for a long time and leads to many chronic
      diseases including cancer, cardiovascular diseases, neurodegenerative diseases,
      respiratory diseases, etc. Numerous lines of evidence suggest that the
      aforementioned risk factors induced cancer through chronic inflammation. First,
      transcription factors NF-kappaB and STAT3 that regulate expression of
      inflammatory gene products, have been found to be constitutively active in most
      cancers; second, chronic inflammation such as pancreatitis, prostatitis,
      hepatitis etc. leads to cancers; third, activation of NF-kappaB and STAT3 leads
      to cancer cell proliferation, survival, invasion, angiogenesis and metastasis;
      fourth, activation of NF-kappaB and STAT3 leads to resistance to chemotherapy and
      radiation, and hypoxia and acidic conditions activate these transcription
      factors. Therefore, targeting these pathways may provide opportunities for both
      prevention and treatment of cancer and other chronic diseases. We will discuss in
      this review the potential of various dietary agents such as spices and its
      components in the suppression of inflammatory pathways and their roles in the
      prevention and therapy of cancer and other chronic diseases. In fact,
      epidemiological studies do indicate that cancer incidence in countries such as
      India where spices are consumed daily is much lower (94/100,000) than those where
      spices are not consumed such as United States (318/100,000), suggesting the
      potential role of spices in cancer prevention.

PMID- 29370863
TI  - Application of the international league against rheumatism classification
      criteria for systemic juvenile idiopathic arthritis as a prognostic factor in
      patients with adults-onset Still's disease.
AB  - BACKGROUND: Adult-onset Still's disease (AOSD) is an adult form of systemic
      juvenile idiopathic arthritis (JIA) that differs from the latter in its
      classification. This study evaluated the concordance between the International
      League Against Rheumatism (ILAR) criteria for systemic JIA and the Yamaguchi
      criteria and then compared their possible prognostic value in patients with AOSD.
      METHODS: In a retrospective review of 169 adults with suspected AOSD, patients
      were classified according to the Yamaguchi or ILAR criteria. Then the concordance
      in cross-referencing the other group with the different criteria was investigated
      and the sensitivity and specificity of each set of criteria were determined.
      Disease activity markers in AOSD patients were correlated with positivity
      according to both systems. RESULTS: Concordance was good in patients with
      suspected AOSD (k = 0.7144, p <  0.001) and low in those with a diagnosis of AOSD
      (k = 0.3787, p <  0.001). The sensitivity of the ILAR criteria in AOSD patients
      was 0.8864 (95% confidence interval (CI): 0.8322-0.9405), and the specificity was
      0.7838 (0.6511, 0.9164). Positivity according to the ILAR criteria correlated
      with the systemic score (r = 0.763, p <  0.0001) and C-reactive protein levels (r
      = 0.183, p = 0.0356) and was associated with a relapse (odds ratio: 1.589, 95%
      CI: 1.043-2.421), macrophage activation syndrome (MAS; odds ratio: 1.993, 95% CI:
      1.218-3.263) and care in the intensive care unit (ICU; odds ratio: 2.087, 95% CI:
      1.086-4.011). CONCLUSIONS: In AOSD patients, there is fair concordance between
      the Yamaguchi and ILAR criteria for systemic JIA. Positive ILAR criteria may be
      useful for identifying AOSD patients at high risk for relapse, MAS and the need
      for ICU care. Further studies including larger populations from several centers
      are needed to confirm our results regarding the utility of the ILAR criteria in
      AOSD patients.

PMID- 29370862
TI  - Towards a universal influenza vaccine: different approaches for one goal.
AB  - Influenza virus infection is an ongoing health and economic burden causing
      epidemics with pandemic potential, affecting 5-30% of the global population
      annually, and is responsible for millions of hospitalizations and thousands of
      deaths each year. Annual influenza vaccination is the primary prophylactic
      countermeasure aimed at limiting influenza burden. However, the effectiveness of
      current influenza vaccines are limited because they only confer protective
      immunity when there is antigenic similarity between the selected vaccine strains
      and circulating influenza isolates. The major targets of the antibody response
      against influenza virus are the surface glycoprotein antigens hemagglutinin (HA)
      and neuraminidase (NA). Hypervariability of the amino acid sequences encoding HA
      and NA is largely responsible for epidemic and pandemic influenza outbreaks, and
      are the consequence of antigenic drift or shift, respectively. For this reason,
      if an antigenic mismatch exists between the current vaccine and circulating
      influenza isolates, vaccinated people may not be afforded complete protection.
      There is currently an unmet need to develop an effective "broadly-reactive" or
      "universal" influenza vaccine capable of conferring protection against both
      seasonal and newly emerging pre-pandemic strains. A number of novel influenza
      vaccine approaches are currently under evaluation. One approach is the
      elicitation of an immune response against the "Achille's heel" of the virus, i.e.
      conserved viral proteins or protein regions shared amongst seasonal and pre
      pandemic strains. Alternatively, other approaches aim toward eliciting a broader
      immune response capable of conferring protection against the diversity of
      currently circulating seasonal influenza strains.In this review, the most
      promising under-development universal vaccine approaches are discussed with an
      emphasis on those targeting the HA glycoprotein. In particular, their strengths
      and potential short-comings are discussed. Ultimately, the upcoming clinical
      evaluation of these universal vaccine approaches will be fundamental to determine
      their effectiveness against preventing influenza virus infection and/or reducing
      transmission and disease severity.

PMID- 29370864
TI  - Leishmaniasis in Sri Lanka: spatial distribution and seasonal variations from
      2009 to 2016.
AB  - BACKGROUND: Leishmaniasis is listed as one of the eight neglected tropical
      diseases by the World Health Organization and the number of cases in endemic
      areas has seen a sharp rise in the past decade. More alarmingly, reports have
      shown that leishmaniasis is spreading to non-endemic areas of the world due to co
      infection with HIV. In Sri Lanka, leishmaniasis is considered as a notifiable
      disease from 2008 and has seen a rising trend of incidence since then. This is
      the first study describing the burden, seasonal variation and spatial
      distribution of leishmaniasis in Sri Lanka since the disease has been included as
      a notifiable disease. METHODS: Data on health statistics from 2009 to 2016 were
      obtained from published databases maintained by the Epidemiology Unit of the
      Ministry of Health in Sri Lanka. Climatic data for Sri Lanka were obtained from
      the Department of Meteorology and the populations in administrative districts
      were obtained from the Department of Census and Statistics, Sri Lanka.
      Descriptive spatiotemporal analysis, correlation between leishmaniasis incidence
      and climatic variables were analyzed using SPSS statistical software. RESULTS:
      The total number of people reported with leishmaniasis during the study period
      was 8487. Cutaneous leishmaniasis is the prominent form in Sri Lanka while few
      visceral and muco-cutaneous cases were reported. Although leishmaniasis patients
      were identified from all 25 districts in the island, almost 90% of the total
      caseload was reported from Anuradhapura, Hambantota, Polonnaruwa, Kurunegala and
      Matara districts. The highest number of patients was reported from the
      Anuradhapura district and the highest incidence per 100,000 persons was reported
      from the Hambantota district. The disease has a seasonal trend, a peak of
      leishmaniasis occur in July to September in the north-central region and in
      October to December in the southern region. Maximum temperature, humidity and
      wind speed are significantly associated climatic variables with leishmaniasis in
      endemic regions. CONCLUSIONS: Leishmaniasis is an emerging public health problem
      in north-central and southern Sri Lanka. Public awareness programs for the
      prevention and control of the disease in endemic regions are essential to reduce
      the incidence of leishmaniasis.

PMID- 29370865
TI  - A mechanism-based pharmacokinetic model of fenofibrate for explaining increased
      drug absorption after food consumption.
AB  - BACKGROUND: Oral administration of drugs is convenient and shows good compliance
      but it can be affected by many factors in the gastrointestinal (GI) system.
      Consumption of food is one of the major factors affecting the GI system and
      consequently the absorption of drugs. The aim of this study was to develop a
      mechanistic GI absorption model for explaining the effect of food on fenofibrate
      pharmacokinetics (PK), focusing on the food type and calorie content. METHODS:
      Clinical data from a fenofibrate PK study involving three different conditions
      (fasting, standard meals and high-fat meals) were used. The model was developed
      by nonlinear mixed effect modeling method. Both linear and nonlinear effects were
      evaluated to explain the impact of food intake on drug absorption. Similarly, to
      explain changes in gastric emptying time for the drug due to food effects was
      evaluated. RESULTS: The gastric emptying rate increased by 61.7% during the first
      6.94 h after food consumption. Increased calories in the duodenum increased the
      absorption rate constant of the drug in fed conditions (standard meal = 16.5%,
      high-fat meal = 21.8%) compared with fasted condition. The final model displayed
      good prediction power and precision. CONCLUSIONS: A mechanistic GI absorption
      model for quantitatively evaluating the effects of food on fenofibrate absorption
      was successfully developed, and acceptable parameters were obtained. The
      mechanism-based PK model of fenofibrate can quantify the effects of food on drug
      absorption by food type and calorie content.

PMID- 29370866
TI  - Trait self-awareness predicts perceptions of choice meaningfulness in a decision
      making task.
AB  - OBJECTIVE: Seminal theorists such as Erikson, Bruner, Frankl and Rogers have
      underscored the importance of meaning in psychological life. However contemporary
      scholars interested in meaning have noted that further investigation of the
      individual differences associated with meaning-making is still needed. In the
      present study we explored whether individual differences in trait self-awareness
      were associated with perceptions of choice meaningfulness in a decision-making
      task. RESULTS: All participants engaged in a decision-making task wherein they
      were asked to choose their preferred painting out of pairs of sequentially
      presented abstract paintings. Participants in the experimental condition were
      provided with feedback that their choices had been diagnostic of important
      personality characteristics whereas those in the control condition were not. All
      participants were then prompted to reflect on their choices before rating the
      subjective meaningfulness that they associated with their choices and completing
      measures to assess trait self-awareness. As anticipated, persons with higher
      levels of trait self-awareness tended to seek out and find more meaning compared
      to those lower in trait self-awareness. However contrary to expectations,
      feedback about the self-relevance of choices did not moderate perceptions of
      choice meaningfulness. Implications of these findings as well as directions for
      future research are also discussed.

PMID- 29370867
TI  - Hybrid blade and locking plate fixation for proximal humerus fractures: a
      comparative biomechanical analysis.
AB  - BACKGROUND: Open reduction and internal fixation of proximal humerus fractures
      can be difficult to achieve adequate, complication free results due to osteopenia
      of the proximal humerus and unstable fracture patterns. This study aimed to
      compare the biomechanical properties of a novel hybrid fixed angle blade plate
      (Fx plate) with an established fixed angle locking plate (PHILOS plate). METHODS:
      A two-part fracture was simulated in synthetic composite humeri by creating a
      transverse osteotomy and 10 mm fracture gap at the surgical neck. After treating
      the fractures with either an Fx plate or a PHILOS plate, humeral head was fixed
      and the shaft was displaced in a cantilever fashion. For elastic tests, loading
      was along the frontal and sagittal plane to achieve varus/valgus and
      extension/flexion, respectively. In plastic tests, loading was in a varus
      direction to determine the constructs' resistance to varus collapse. RESULTS: In
      elastic tests, both construct types had higher peak load and stiffness in
      extension/flexion than varus/valgus. Fx plate constructs were significantly
      stiffer than PHILOS constructs in varus/valgus (mean: 7.590/6.900 vs. 6.609/6.091
      N/mm; p < 0.001 for both) but significantly less stiff in extension/flexion
      (8.770/9.541 vs. 9.533/9.997 N/mm; p < 0.001 for extension, p < 0.05 for
      flexion). In varus plastic tests, significantly higher peak loads were reported
      for Fx plate than PHILOS (134.391 vs. 115.531 N; p < 0.001). CONCLUSIONS: In this
      fracture gap model, humeri implanted with a novel Fx plate provided higher
      varus/valgus stiffness but lower extension/flexion stiffness than a more
      traditional proximal humeral locking plate design (PHILOS).

PMID- 29370869
TI  - A new enzyme-linked immunosorbent assay for neurofilament light in cerebrospinal
      fluid: analytical validation and clinical evaluation.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light (NfL) is a reliable
      marker of neuro-axonal damage in different neurological disorders that is related
      to disease severity. To date, all recent studies performed in human CSF have used
      the same enzyme-linked immunosorbent assay (ELISA). To confirm the large body of
      evidence for NfL, we developed a new ELISA method and here we present the
      performance characteristics of this new ELISA for CSF NfL in different
      neurological disorders. METHODS: We produced two monoclonal antibodies (NfL21 and
      NfL23) directed against the NfL core domain, and developed a novel sandwich ELISA
      method that we evaluated in patients with: 1) inflammatory demyelinating diseases
      (IDD; n = 97), including multiple sclerosis (MS; n = 59), clinically isolated
      syndrome (CIS; n = 32), and radiologically isolated syndrome (RIS; n = 6); 2)
      Alzheimer's disease (AD; n = 72), including mild cognitive impairment due to AD
      (MCI-AD, n = 36) and probable AD dementia (AD-dem; n = 36); 3) Parkinson's
      disease (PD; n = 30); and 4) other neurological noninflammatory and non
      neurodegenerative diseases (OND; n = 30). RESULTS: Our new NfL ELISA showed a
      good analytical performance (inter-plate coefficient of variation (CV) < 13%),
      with no cross-reactivity with neurofilament medium and heavy (NfM and NfH). With
      respect to the other available ELISAs, CSF NfL showed the same range of values
      with a strong correlation (r = 0.9984, p < 0.001) between the two methods. CSF
      NfL levels were significantly higher in MCI-AD/AD-dem and IDD patients as
      compared with both PD and OND patients. The highest discriminative power was
      obtained between IDD and OND patients (area under the curve (AUC) 0.87, 95%
      confidence interval (CI) 0.80-0.95). Within the IDD group, CSF NfL positively
      correlated with several clinical and radiological disease severity parameters.
      CONCLUSIONS: These results show a good analytical performance of the new ELISA
      for quantification of NfL concentrations in the CSF. CSF NfL is confirmed to be a
      reliable marker in AD and MS, and a disease-severity marker in MS patients.

PMID- 29370868
TI  - mRNA export in the apicomplexan parasite Toxoplasma gondii: emerging divergent
      components of a crucial pathway.
AB  - Control of gene expression is crucial for parasite survival and is the result of
      a series of processes that are regulated to permit fine-tuning of gene expression
      in response to biological changes during the life-cycle of apicomplexan
      parasites. Control of mRNA nuclear export is a key process in eukaryotic cells
      but is poorly understood in apicomplexan parasites. Here, we review recent
      knowledge regarding this process with an emphasis on T. gondii. We describe the
      presence of divergent orthologs and discuss structural and functional differences
      in export factors between apicomplexans and other eukaryotic lineages.
      Undoubtedly, the use of the CRISPR/Cas9 system in high throughput screenings
      associated with the discovery of mRNA nuclear export complexes by proteomic
      analysis will contribute to identify these divergent factors. Ligand-based or
      structure-based strategies may be applied to investigate the potential use of
      these proteins as targets for new antiprotozoal agents.

PMID- 29370870
TI  - Diffusion kurtosis imaging allows the early detection and longitudinal follow-up
      of amyloid-beta-induced pathology.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      and the most common cause of dementia in the elderly population. In this study,
      we used the APP/PS1 transgenic mouse model to explore the feasibility of using
      diffusion kurtosis imaging (DKI) as a tool for the early detection of
      microstructural changes in the brain due to amyloid-beta (Abeta) plaque
      deposition. METHODS: We longitudinally acquired DKI data of wild-type (WT) and
      APP/PS1 mice at 2, 4, 6 and 8 months of age, after which these mice were
      sacrificed for histological examination. Three additional cohorts of mice were
      also included at 2, 4 and 6 months of age to allow voxel-based co-registration
      between diffusion tensor and diffusion kurtosis  metrics and
      immunohistochemistry. RESULTS: Changes were observed in diffusion tensor (DT) and
      diffusion kurtosis (DK) metrics in many of the 23 regions of interest that were
      analysed. Mean and axial kurtosis were greatly increased owing to Abeta-induced
      pathological changes in the motor cortex of APP/PS1 mice at 4, 6 and 8 months of
      age. Additionally, fractional anisotropy (FA) was decreased in APP/PS1 mice at
      these respective ages. Linear discriminant analysis of the motor cortex data
      indicated that combining diffusion tensor and diffusion kurtosis metrics permits
      improved separation of WT from APP/PS1 mice compared with either diffusion tensor
      or diffusion kurtosis metrics alone. We observed that mean kurtosis and FA are
      the critical metrics for a correct genotype classification. Furthermore, using a
      newly developed platform to co-register the in vivo diffusion-weighted magnetic
      resonance imaging with multiple 3D histological stacks, we found high
      correlations between DK metrics and anti-Abeta (clone 4G8) antibody, glial
      fibrillary acidic protein, ionised calcium-binding adapter molecule 1 and myelin
      basic protein immunohistochemistry. Finally, we observed reduced FA in the septal
      nuclei of APP/PS1 mice at all ages investigated. The latter was at least
      partially also observed by voxel-based statistical parametric mapping, which
      showed significantly reduced FA in the septal nuclei, as well as in the corpus
      callosum, of 8-month-old APP/PS1 mice compared with WT mice. CONCLUSIONS: Our
      results indicate that DKI metrics hold tremendous potential for the early
      detection and longitudinal follow-up of Abeta-induced pathology.

PMID- 29370871
TI  - Data-driven identification of endophenotypes of Alzheimer's disease progression:
      implications for clinical trials and therapeutic interventions.
AB  - BACKGROUND: Given the complex and progressive nature of Alzheimer's disease (AD),
      a precision medicine approach for diagnosis and treatment requires the
      identification of patient subgroups with biomedically distinct and actionable
      phenotype definitions. METHODS: Longitudinal patient-level data for 1160 AD
      patients receiving placebo or no treatment with a follow-up of up to 18 months
      were extracted from an integrated clinical trials dataset. We used latent class
      mixed modelling (LCMM) to identify patient subgroups demonstrating distinct
      patterns of change over time in disease severity, as measured by the Alzheimer's
      Disease Assessment Scale-cognitive subscale score. The optimal number of
      subgroups (classes) was selected by the model which had the lowest Bayesian
      Information Criterion. Other patient-level variables were used to define these
      subgroups' distinguishing characteristics and to investigate the interactions
      between patient characteristics and patterns of disease progression. RESULTS: The
      LCMM resulted in three distinct subgroups of patients, with 10.3% in Class 1,
      76.5% in Class 2 and 13.2% in Class 3. While all classes demonstrated some degree
      of cognitive decline, each demonstrated a different pattern of change in
      cognitive scores, potentially reflecting different subtypes of AD patients. Class
      1 represents rapid decliners with a steep decline in cognition over time, and who
      tended to be younger and better educated. Class 2 represents slow decliners,
      while Class 3 represents severely impaired slow decliners: patients with a
      similar rate of decline to Class 2 but with worse baseline cognitive scores.
      Class 2 demonstrated a significantly higher proportion of patients with a history
      of statins use; Class 3 showed lower levels of blood monocytes and serum calcium,
      and higher blood glucose levels. CONCLUSIONS: Our results, 'learned' from
      clinical data, indicate the existence of at least three subgroups of Alzheimer's
      patients, each demonstrating a different trajectory of disease progression. This
      hypothesis-generating approach has detected distinct AD subgroups that may prove
      to be discrete endophenotypes linked to specific aetiologies. These findings
      could enable stratification within a clinical trial or study context, which may
      help identify new targets for intervention and guide better care.

PMID- 29370872
TI  - Cyathostomine egg reappearance period following ivermectin treatment in a cohort
      of UK Thoroughbreds.
AB  - BACKGROUND: In spite of the emergence of populations of drug-resistant
      cyathostomines worldwide, little is known of parasite species responsible for
      'early egg shedding' in cohorts of horses subjected to treatment with widely used
      anthelmintics, e.g. ivermectin (IVM). In this study, we determined the
      cyathostomine egg reappearance period (ERP) after IVM treatment in a cohort of
      yearlings from a large Thoroughbred (TB) stud farm in the United Kingdom, and
      identified species of cyathostomines with reduced ERP using a combination of
      fundamental parasitology techniques coupled with advanced molecular tools.
      METHODS: Individual faecal samples were collected from TB yearlings with
      cyathostomine infection prior to IVM treatment, as well as at 14, 21, 28, 35, 42
      and 49 days post-treatment. Faecal egg counts (FEC) were performed for each
      individual sample for determination of ERPs. In addition, individual larval
      cultures were performed and representative numbers of third-stage larvae (L3s)
      harvested from each culture were subjected to molecular species identification
      via PCR-Reverse Line Blot (RLB). RESULTS: Prior to IVM treatment, 11
      cyathostomine species were detected in faecal samples from TB horses enrolled in
      this study, i.e. Cyathostomum catinatum, Cylicostephanus longibursatus,
      Cylicostephanus goldi, Cylicocyclus nassatus, Cylicostephanus calicatus,
      Cyathostomum pateratum, Cylicocyclus radiatus, Paraposteriostomum mettami,
      Coronocyclus labratus, Cylicocyclus insigne and Cylicocyclus radiatus variant A.
      Of these, eggs of Cya. catinatum, Cys. longibursatus, Cyc. nassatus and Cyc.
      radiatus could be detected at 28 days post-treatment, while from day 42 onwards,
      cyathostomine species composition reflected data obtained pre-IVM treatment, with
      the exception of eggs of Cor. labratus and Cyc. insigne which could no longer be
      detected post-IVM administration. CONCLUSIONS: This study provides valuable data
      on the occurrence of IVM-resistance in cyathostomines in the UK. Nevertheless,
      further investigations are needed to shed light on the prevalence and incidence
      of drug-resistance in this country, as well as other areas of the world where
      equine trade is substantial.

PMID- 29370873
TI  - Phylogenetic analysis of apicomplexan parasites infecting commercially valuable
      species from the North-East Atlantic reveals high levels of diversity and
      insights into the evolution of the group.
AB  - BACKGROUND: The Apicomplexa from aquatic environments are understudied relative
      to their terrestrial counterparts, and the seminal work assessing the
      phylogenetic relations of fish-infecting lineages is mostly based on freshwater
      hosts. The taxonomic uncertainty of some apicomplexan groups, such as the
      coccidia, is high and many genera were recently shown to be paraphyletic,
      questioning the value of strict morphological and ecological traits for parasite
      classification. Here, we surveyed the genetic diversity of the Apicomplexa in
      several commercially valuable vertebrates from the North-East Atlantic, including
      farmed fish. RESULTS: Most of the sequences retrieved were closely related to
      common fish coccidia of Eimeria, Goussia and Calyptospora. However, some lineages
      from the shark Scyliorhinus canicula were placed as sister taxa to the Isospora,
      Caryospora and Schellakia group. Additionally, others from Pagrus caeruleostictus
      and Solea senegalensis belonged to an unknown apicomplexan group previously found
      in the Caribbean Sea, where it was sequenced from the water column, corals, and
      fish. Four distinct parasite lineages were found infecting farmed Dicentrarchus
      labrax or Sparus aurata. One of the lineages from farmed D. labrax was also found
      infecting wild counterparts, and another was also recovered from farmed S. aurata
      and farm-associated Diplodus sargus. CONCLUSIONS: Our results show that marine
      fish apicomplexans are diverse, and we highlight the need for a more extensive
      assessment of parasite diversity in this phylum. Additionally, parasites
      recovered from S. canicula were recovered as basal to their piscine counterparts
      reflecting hosts phylogeny.

PMID- 29370876
TI  - The Development and Psychometric Evaluation of the Group Schema Therapy Rating
      Scale - Revised.
AB  - BACKGROUND: Recent research has supported the efficacy of schema therapy as a
      treatment for personality disorders. A group format has been developed (group
      schema therapy; GST), which has been suggested to improve both the clinical and
      cost-effectiveness of the treatment. AIMS: Efficacy studies of GST need to assess
      treatment fidelity. The aims of the present study were to improve, describe and
      evaluate a fidelity measure for GST, the Group Schema Therapy Rating Scale -
      Revised (GSTRS-R). METHOD: Following a pilot study on an initial version of the
      scale (GSTRS), items were revised and guidelines were modified in order to
      improve the reliability of the scale. Students highly experienced with the scale
      rated recorded GST therapy sessions using the GSTRS-R in addition to a group
      cohesion measure, the Harvard Community Health Plan Group Cohesiveness Scale - II
      (GCS-II). The scores were used to assess internal consistency and inter-rater
      reliability. Discriminant validity was assessed by comparing the scores on the
      GSTRS-R with the GCS-II. RESULTS: The GSTRS-R displayed substantial internal
      consistency and inter-rater reliability, and adequate discriminate validity,
      evidenced by a weak positive correlation with the GCS-II. CONCLUSIONS: Overall,
      the GSTRS-R is a reliable tool that may be useful for evaluating therapist
      fidelity to GST model, and assisting GST training and supervision. Initial
      validity was supported by a weak association with GCS-II, indicating that
      although associated with cohesiveness, the instrument also assesses factors
      specific to GST. Limitations are discussed.

PMID- 29370877
TI  - Can history improve big bang health reform? Commentary.
AB  - At present, the professional skills of the historian are rarely relied upon when
      health policies are being formulated. There are numerous reasons for this, one of
      which is the natural desire of decision-makers to break with the past when
      enacting big bang policy change. This article identifies the strengths
      professional historians bring to bear on policy development using the
      establishment and subsequent reform of universal health coverage as an example.
      Historians provide pertinent and historically informed context; isolate the
      forces that have historically allowed for major reform; and separate the truly
      novel reforms from those attempted or implemented in the past. In addition, the
      historian's use of primary sources allows potentially new and highly salient
      facts to guide the framing of the policy problem and its solution. This paper
      argues that historians are critical for constructing a viable narrative of the
      establishment and evolution of universal health coverage policies. The lack of
      this narrative makes it difficult to achieve an accurate assessment of systemic
      gaps in coverage and access, and the design or redesign of universal health
      coverage that can successfully close these gaps.

PMID- 29370875
TI  - Substance use patterns and in-hospital care of adolescents and young adults
      attending music concerts.
AB  - BACKGROUND: Few studies describe medical complaints and substance use patterns
      related to attending music concerts. As such, the objective of this study is to
      describe patient demographics, substance use and intoxication patterns, and
      medical interventions provided to adolescents and young adults assessed in an
      emergency department (ED) for complaints directly related to concert attendance.
      METHODS: A retrospective chart review of patients 13-30 years old who were
      transported to the ED directly from music concerts between January 2011 and
      December 2015 was conducted. Descriptive statistics and logistic regression were
      used to analyze patient demographic, intervention, and substance use data.
      RESULTS: There were 115 concerts identified, of which 48 (42%) were linked to 142
      relevant ED visits; the total number of attendees at each concert is unknown. The
      mean age of the 142 described patients was 19.5 years (SD 3.3) with 72% < 21 and
      33% < 18; 71% of patients were female and 96% of visits were substance-use
      related. Mean blood alcohol level was 242 mg/dL (range 104-412, SD 70). Glasgow
      Coma Scale (GCS) scores ranged from 3 to 15, with a mean of 14. Two patients
      required intubation and 61% of patients received interventions, including
      medications (47%), intravenous fluids (46%), specialty consultation (20%),
      restraints (14%), imaging (6%), and laceration repair (3%). Attendance at pop and
      electronic dance music concerts was associated with the widest ranges of GCS
      scores (8-15 and 6-14 respectively), mass casualty incident declarations, and
      among the highest mean blood alcohol levels (246 and 244 mg/dL, respectively).
      CONCLUSIONS: Substance use is the predominant reason for music concert related ED
      visits and patients may have serious levels of intoxication, receiving multiple
      medical interventions. These data demonstrate the need for additional large-scale
      studies to confirm trends and increase awareness of this important public health
      problem.

PMID- 29370874
TI  - International practices in the dietary management of fructose 1-6 biphosphatase
      deficiency.
AB  - BACKGROUND: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims
      to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting,
      particularly during febrile illness. Although the need for an emergency regimen
      to avoid metabolic decompensation is well established at times of illness, there
      is uncertainty about the need for other dietary management strategies such as
      sucrose or fructose restriction. We assessed international differences in the
      dietary management of FBPase deficiency. METHODS: A cross-sectional questionnaire
      (13 questions) was emailed to all members of the Society for the Study of Inborn
      Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder
      dietitians. RESULTS: Thirty-six centres reported the dietary prescriptions of 126
      patients with FBPase deficiency. Patients' age at questionnaire completion was: 1
      10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age
      was: <1y, 36% (n = 46); 1-10y, 59% (n = 74); 11-16y, 3% (n = 4); and >16y, 2% (n
      = 2). Seventy-five per cent of centres advocated dietary restrictions. This
      included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and
      sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%).
      Twenty-five per cent of centres (n = 9), advised no dietary restrictions when
      patients were well. A higher percentage of patients aged >16y rather than <=16y
      were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11
      16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a
      normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y,
      and 58% in >16y, but it was unclear if fasting tolerance was biochemically
      proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to
      limit overnight fasting in 47 patients regardless of their actual fasting
      tolerance (37%). All centres advocated an emergency regimen mainly based on
      glucose polymer for illness management. CONCLUSIONS: Although all patients were
      prescribed an emergency regimen for illness, use of sucrose and fructose
      restricted diets with UCCS supplementation varied widely. Restrictions did not
      relax with age. International guidelines are necessary to help direct future
      dietary management of FBPase deficiency.

PMID- 29370878
TI  - Does the distribution frequency matter? A subgroup specific analysis of the
      effectiveness of the EU School Fruit and Vegetable Scheme in Germany comparing
      twice and thrice weekly deliveries.
AB  - OBJECTIVE: The present study aimed to examine the effectiveness of two different
      implementation forms of the EU School Fruit and Vegetable Scheme (SFVS). DESIGN:
      A quasi-experimental design was applied including a thrice as well as a twice
      weekly intervention group. Repeated 24 h dietary recalls were used to measure
      children's fruit and vegetable (F&V) intake. Effects were analysed on days with
      and without F&V deliveries using hierarchical linear regression models. SETTING:
      Twelve primary schools in North Rhine-Westphalia, Germany. SUBJECTS: Third and
      fourth graders (n 664). RESULTS: Average daily F&V intake at pre-intervention was
      0.84 frequencies in the thrice weekly intervention group, 0.90 frequencies in the
      twice weekly intervention group and 1.25 frequencies in the control group.
      Providing children thrice weekly with F&V increased children's F&V intake on
      average by 0.96 (P<0.001) frequencies/d. The effects were higher on days with
      (1.07; P<0.001) than on days without (0.75; P<0.001) F&V deliveries. Distributing
      F&V twice weekly resulted in an increase of 0.75 (P<0.001) frequencies/d on
      average, again with higher effects on days with (1.30; P<0.001) than without
      (0.48; P<0.003) F&V deliveries. Subgroup analysis revealed some indications for
      differential effectiveness only in the twice weekly intervention group.
      CONCLUSIONS: The SFVS with thrice or twice weekly deliveries of F&V led to a
      significant increase in children's F&V intake on days with and without
      deliveries. The latter might provide an indication of positive long-term effects
      of the scheme. The scheme shows equal efficiency for almost all subgroups.

PMID- 29370880
TI  - Association Between HLA genotypes and Oxcarbazepine-induced Cutaneous Adverse
      Drug Reactions: A Systematic Review and Meta-Analysis.
AB  - PURPOSE: To systematically review and quantitatively synthesize associations
      between HLA genotypes and oxcarbazepine-induced cutaneous adverse drug reactions
      (OXC-cADRs), including Stevens-Johnson syndrome (SJS) and maculopapular rash.
      METHODS: Studies investigating associations between HLA genotypes and OXC-cADRs
      were systematically searched irrespective of language, in PubMed, HuGENet (Human
      Genome Epidemiology Network), and the Cochrane Library from their inception until
      January, 2017. Inclusion criteria were studies investigating associations between
      HLA genotypes and OXC-cADRs that reported sufficient data for calculating the
      frequency of HLA genotype carriers among cases and controls. Overall odds ratios
      (ORs) with corresponding 95%CIs were calculated using a random-effects model to
      determine the association between HLA genotypes and OXC-cADRs.  RESULTS: The
      initial searches identified 91 articles, of which 6 studies met the selection
      criteria. The studies included 229 patients with OXC-cADRs, 251 OXC-tolerant
      patients, and 2,358 participants from general populations of Han Chinese, Korean,
      and Thai ethnicities.  Associations between HLA-B*1502 and OXC-induced SJS were
      found in both the general population [OR=30.2 (95%CI=3.45-264)] and in OXC
      tolerant individuals [OR=26.4 (95%CI=7.98-87.6)]. An association between the HLA
      B*1502 and OXC-induced maculopapular rash was found in the general population
      [OR=5.67 (95%CI=2.03-15.9)] while HLA-A*3101 also associated with OXC-induced
      maculopapular rash [overall OR=29.2 (95%CI=6.70-128)].  CONCLUSIONS: Strong
      associations between the HLA-B*1502 and OXC-cADRs (SJS and maculopapular rash)
      were found in both controls from general population and OXC-tolerant groups.
      There was also an association between HLA-B*3101 and OXC-induced maculopapular
      rash. For patient safety, genetic screening especially for HLA-B*1502 prior to
      OXC therapy at least in these closely related ethnicities is warranted. Further
      studies need to better define other ethnicities at risk and a wider range of MHC
      gene subtypes. This article is open to POST-PUBLICATION REVIEW. Registered
      readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's
      contents page.

PMID- 29370881
TI  - Discussion of "Dual energy computed tomography should be the first line
      preoperative localization imaging test for primary hyperparathyroidism patients".

PMID- 29370879
TI  - Differential epitope masking reveals synapse-specific complexes of TRPM1.
AB  - The transient receptor potential channel TRPM1 is required for synaptic
      transmission between photoreceptors and the ON subtype of bipolar cells (ON-BPC),
      mediating depolarization in response to light. TRPM1 is present in the somas and
      postsynaptic dendritic tips of ON-BPCs. Monoclonal antibodies generated against
      full-length TRPM1 were found to have differential labeling patterns when used to
      immunostain the mouse retina, with some yielding reduced labeling of dendritic
      tips relative to the labeling of cell bodies. Epitope mapping revealed that those
      antibodies that poorly label the dendritic tips share a binding site (N2d) in the
      N-terminal arm near the transmembrane domain. A major splice variant of TRPM1
      lacking exon 19 does not contain the N2d binding site, but quantitative
      immunoblotting revealed no enrichment of this variant in synaptsomes. One
      explanation of the differential labeling is masking of the N2d epitope by
      formation of a synapse-specific multiprotein complex. Identifying the binding
      partners that are specific for the fraction of TRPM1 present at the synapses is
      an ongoing challenge for understanding TRPM1 function.

PMID- 29370882
TI  - Metastases treated with surgery alone: A dream come true?

PMID- 29370883
TI  - Discussion of "Institutional review of the implementation and use of a
      Clostridium difficile infection bundle and probiotics in adult trauma patients".

PMID- 29370884
TI  - Risk of major complications following thyroidectomy and parathyroidectomy:
      Utility of the NSQIP surgical risk calculator.
AB  - BACKGROUND: The primary objective of this study was to determine rates of
      reoperation, ED visits, and hospital readmission after thyroid and parathyroid
      surgery at a tertiary hospital. A secondary objective was to determine if scores
      from the American College of Surgeons Surgical Risk Calculator (ACS SRC)
      predicted these events. METHODS: We retrospectively reviewed the records of
      patients undergoing parathyroid and thyroid surgery between 2011 and 2014.
      Patients who underwent an unplanned reoperation, returned to the ED, or were
      readmitted to hospital were evaluated using the ACS SRC. RESULTS: 436 patients
      underwent thyroid and parathyroid operations. Rates of re-operations, ED visits
      and hospital readmissions after thyroid and parathyroid surgery were: 3.4%, 0.6%
      and 3.0% and 2.2%, 0% and 1.4%, respectively. 71% of patients who experienced
      post-operative complications scored below average on the ACS SRC, 17% scored
      above average and 12% scored average risk. CONCLUSIONS: The SRC did not predict
      re-operation, ED visits, or hospital readmission after thyroid or parathyroid
      operations.

PMID- 29370885
TI  - Assessment of extracranial and intracranial atherosclerosis: Don't dismiss old
      school autopsy.

PMID- 29370886
TI  - Functional outcome and health related quality of life after dual mobility cup
      total hip replacement for displaced femoral neck fractures in middle aged
      Egyptian patients.
AB  - AIM: This study was done to assess the functional and clinical results after one
      year of cemented THR with dual mobility cup for the treatment of fracture neck
      femur in active middle-aged patients in Egypt (Middle Eastern population).
      PATIENTS AND METHODS: This study included 31 patients (32 hips) with displaced
      femoral neck fractures that were admitted to El Hadara University Hospital,
      Alexandria, Egypt. Their mean age was 66.4 +/- 5.9 years. Fifteen patients were
      females. All the patients were treated with total hip replacement using a
      cemented dual mobility cup (Ecofit(r) 2 M, Implantcast GmbH, Germany) total hip
      replacement through the standard posterior approach. Functional assessment was
      done using Harris Hip Score (HHS), SF-36 questionnaire for health related quality
      of life (HRQoL) with assistance of a physiotherapist. RESULTS: The mean HHS
      improved over the follow up period from 79.04 +/- 7.9 at 12 weeks to an average
      of 92.8 +/- 11.1 at 1 year follow up. HRQoL measures showed a pattern of initial
      drop at 3 months postoperatively, then a steady rise to be restored at 1 year as
      compared to the preoperative baseline measures. There were no dislocations
      encountered in this series over one year follow up. The following complications
      were encountered; 1 deep infection, 2 deep vein thrombosis, 2 heterotopic
      ossifications, and 1 patient died within one year after surgery. CONCLUSIONS:
      Dual mobility cup total hip replacement is an acceptable method for treatment of
      displaced femoral neck fracture in active middle aged patients in Egypt as it
      provides pain relief and good function without compromising the stability.

PMID- 29370887
TI  - The Myasthenia Gravis-specific Activities of Daily Living scale as a useful
      outcome measure and in routine clinical management in Polish patients.
AB  - INTRODUCTION: The Myasthenia Gravis-Activities of Daily Living scale (MG-ADL) is
      a short, and easy to use disease-specific quality of life during daily routine
      tool in myasthenia gravis. OBJECTIVES: The purpose of our work was to evaluate
      neurological condition patients with myasthenia gravis using the form MG-ADL in
      order to enable the introduction in common use of an instrument which allows for
      the assessment of patients with myasthenia gravis. PATIENTS AND METHODS: The
      total number of 50 patients with MG were qualified for the examination. Each
      patient underwent neurological examination and completed the quality of life
      evaluation questionnaire MQ-ADL. Additionally, each patient was asked to evaluate
      the quality of his/her life by means of questionnaire MG-QOL 15 and MG Composite
      in Polish language version. RESULTS: Our analysis showed a positive correlation
      with other scales used - MG-QOL 15, MGFA, MG Composite. The intensification of
      neurological symptoms showed significant relation with obtained higher number of
      points in MG-ADL questionnaire. The MG-ADL was found to have high internal
      consistency, test-retest reliability, and concurrent validity. CONCLUSION: We
      confirmed reliability and dependability of the questionnaire in the the test
      retest assessment. The MG-ADL is accepted to be a reliable and valuable tool for
      measuring disease-specific QOL in Polish patients with MG.

PMID- 29370888
TI  - Lack of association between rheumatoid arthritis and genetic variants rs10889677,
      rs11209026 and rs2201841 of IL-23R gene.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune diseases, where
      different genetic variants in cytokine genes may play a pathogenic role. A GWAS
      in autoimmune diseases highlighted the IL-23R gene as a one of the susceptibility
      factors. We examined three candidate single nucleotide polymorphisms (SNPs)
      rs10889677, rs11209026 and rs2201841 of the IL-23R gene, as well as determined
      their possible association with RA in a Polish population. PATIENTS AND METHODS:
      The IL-23R gene polymorphisms were genotyped for 422 RA patients and 348 healthy
      individuals using TaqMan SNP genotyping assay. RESULTS: The genotypes frequency
      did not deviate from HWE in each examined group. A comparison of the allele as
      well as genotype frequencies of the IL-23R polymorphisms under codominant,
      dominant and recessive genetic model revealed no significant differences between
      RA patients and healthy subjects. We also demonstrated that IL-23R rs2201841 and
      rs11209026 as well as rs11209026 and rs10889677 were in complete linkage
      disequilibrium (D'=1.0). Our genotype-phenotype analysis demonstrated that in
      carriers of rs10889677C and/or rs2201841A allele the RF, extra-articular
      manifestations and erosion were more frequent present than in patients with
      rs10889677A and/or rs2201841A allele, although this association was not
      significant. DISCUSSION: Present findings indicated that the autoimmune disease
      associated genetic variants in IL-23R gene are not associated with RA in the
      Polish population.

PMID- 29370889
TI  - Alveolar Macrophages.
AB  - Alveolar macrophages are the most abundant innate immune cells in the distal lung
      parenchyma, located on the luminal surface of the alveolar space. They are the
      first to encounter incoming pathogens and pollutants and to help orchestrate the
      initiation and resolution of the immune response in the lung. Similar to other
      tissue-resident macrophages, alveolar macrophages also perform non-immune, tissue
      specific, homeostatic functions, most notably clearance of surfactant. In this
      review we will discuss how ontogeny and local lung environment shape the role of
      alveolar macrophages in health and disease.

PMID- 29370890
TI  - Clinical outcomes after tracheoplasty in patients with congenital tracheal
      stenosis in 1997-2014.
AB  - BACKGROUND: Mortality and morbidity of congenital tracheal stenosis (CTS) remain
      high. The aim of this study was to determine the factors predicting 12-month
      survival and 2-month successful extubation after tracheoplasty in patients with
      CTS. METHODS: Retrospective chart reviews were conducted in patients with CTS
      undergoing tracheoplasty at a single institution between 1997 and 2014. Patients'
      characteristics at disease onset and tracheoplasty were summarized. Twelve-month
      survival rate and 2-month extubation rate without tracheotomy after tracheoplasty
      were analyzed. RESULTS: We reviewed 81 patients' records. Multivariate analysis
      for 12-month survival revealed that older age (>2 months, hazard ratio [HR]:
      0.08, 95% confidence interval [CI]: 0.02-0.36) or heavier body weight (>4.4 kg,
      HR: 0.13, 95% CI: 0.02-0.73) at tracheoplasty was a predictive factor for
      survival. Body weight at tracheoplasty (>8.2 kg, HR: 3.83, 95% CI: 1.88-7.79),
      preoperative balloon dilatation (HR: 0.30, 95% CI: 0.12-0.78), and carina
      involvement (HR: 0.36, 95% CI: 0.19-0.69) were predictive factors for successful
      extubation. CONCLUSIONS: Although CTS management is individualized, age or body
      weight at tracheoplasty needs to be considered and assessed for survival, as well
      as preoperative balloon dilatation, and carina involvement for successful
      extubation. LEVELS OF EVIDENCE: Level III.

PMID- 29370891
TI  - Risk factors for venous thromboembolic events in pediatric surgical patients:
      Defining indications for prophylaxis.
AB  - BACKGROUND: Venous thromboembolism (VTE) in pediatric surgical patients is a rare
      event. The risk factors for VTE in pediatric general surgery patients undergoing
      abdominopelvic procedures are unknown. STUDY DESIGN: The American College of
      Surgeon's National Surgical Quality Improvement Program-Pediatric (NSQIP-P)
      database (2012-2015) was queried for patients with VTE after abdominopelvic
      general surgery procedures. Patient and operative variables were assessed to
      identify risk factors associated with VTE and develop a pediatric risk score.
      RESULTS: From 2012-2015, 68 of 34,813 (0.20%) patients who underwent
      abdominopelvic general surgery procedures were diagnosed with VTE. On
      multivariate analysis, there was no increased risk of VTE based on concomitant
      malignancy, chemotherapy, inflammatory bowel disease, or laparoscopic surgical
      approach, while a higher rate of VTE was identified among female patients. The
      odds of experiencing VTE were increased on stepwise regression for patients older
      than 15 years and those with preexisting renal failure or a diagnosis of septic
      shock, patients with American Society of Anesthesia (ASA) classification >= 2,
      and for anesthesia time longer than 2 h. The combination of age > 15 years, ASA
      classification >= 2, anesthesia time > 2 h, renal failure, and septic shock was
      included in a model for predicting risk of VTE (AUC = 0.907, sensitivity 84.4%,
      specificity 88.2%). CONCLUSION: VTE is rare in pediatric patients, but prediction
      modeling may help identify those patients at heightened risk. Additional studies
      are needed to validate the factors identified in this study in a risk assessment
      model as well as to assess the efficacy and cost-effectiveness of prophylaxis
      methods. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

PMID- 29370892
TI  - Laparoscopic one port appendectomy: Evaluation in pediatric surgery.
AB  - BACKGROUND: Appendectomy is a well-established surgical procedure in pediatric
      surgery used in the management of acute appendicitis. With the continuous
      advancement in the field of minimal invasive surgery, the recent focus is on
      single incision laparoscopic (SIL) surgery. SILA also goes further in order to
      decrease pain, improve recovery and enhance patient satisfaction. However, this
      approach is still not a well-established technique and not widely practiced,
      especially in pediatric surgery. METHODS: We prospectively recorded the data in
      our pediatric universitary hospital center since January, 01 2017 to July, 01
      2017. Patients included in this study were randomized in two groups: SILA group
      (managed by one-port laparoscopy, n=40) and LA group (conventional laparoscopy
      using three trocars, n=40). RESULTS: The mean operative time for SILA was
      significantly lower. There were no postoperative complications in SILA group. If
      peritonitis was associated with appendicitis, the operative duration was not
      significantly different between each group. The duration in recovery room after
      surgery was significantly lower in SILA group. The morphine consumption was
      significantly lower for SILA group according to patient weight. SILA is less
      painful significantly than CLA for the first postoperative 6 h. After, even if
      SILA appears less painful, difference is not significant. The hospital length of
      stay was significantly higher in LA than SILA group CONCLUSIONS: SILA procedure
      for appendectomy appears to be safe and efficient for appendicitis management in
      children. This technique could be applied in routine as in emergency tome. TYPE
      OF STUDY: Prospective comparative study LEVEL OF EVIDENCE: II.

PMID- 29370893
TI  - Reply to Letter to the Editor.

PMID- 29370894
TI  - Continence after posterior sagittal anorectoplasty for anorectal malformations:
      comparison of different scores.
AB  - PURPOSE: To evaluate bowel function in patients with anorectal malformations
      (ARM) comparing existing scoring systems. METHODS: Parents of ARM patients
      treated at our institution were asked to fill in Holschneider, Kricknebeck, and
      Rintala questionnaires. Scores obtained from the questionnaires were expressed
      per cent and analyzed depending on the age and type of ARM according to
      Krickenbeck classification. Patients younger than 3 years of age or with
      developmental delay were excluded. RESULTS: Eighty patients (42 males: 52%) were
      included. Median age was 7.6 years (range 3-22). Twenty eight patients (35%) had
      perineal fistula, 13 (16%) bulbar, 7 (9%) prostatic, 5 (6%) rectobladder neck, 15
      (19%) vestibular, 7 (9%) had a cloaca and 5 (6%) imperforate anus without
      fistula. Using Holschneider, Krickenbeck, and Rintala, average scores were
      respectively 72, 71 and 73 (p = 0.4 with ANOVA). Using the three questionnaires
      patients with perineal fistula scored 82, 76 and 84 respectively (p = 0.003),
      with bulbar 70, 71, 73 (p = 0.8), with prostatic 52,69,59 (p = 0.06), with
      bladder neck 56, 80, 57 (p = 0.004), with vestibular 75,67,75 (p = 0.02), with
      cloaca 64, 67, 65 (p = 0.9), and with imperforate anus without fistula 61,49, 53
      (p = 0.12). Patients from 3 to 6 years of age scored 74,72 and 76 (p = 0.37),
      from 7 to 12: 70,71 and 71 (p = 0.87), and older than twelve: 74,66 e 73 (p =
      0.08). CONCLUSION: The scores obtained using Holschneider, Rintala, and
      Krickenbeck questionnaires are significantly lower with increasing severity of
      the ARM. For each type of ARM there are some differences in the results obtained
      using the three questionnaires. In general, Krickenbeck and Pena questionnaires
      tend to give lower scores in patients with ARMs that have good prognosis, and
      higher scores for ARMs with poor prognosis. Age is not significantly related to
      the score obtained. LEVEL OF EVIDENCE: III TYPE OF STUDY: Diagnostic study.

PMID- 29370895
TI  - Pelvic and lower extremity immobilization for cloacal exstrophy bladder and
      abdominal closure in neonates and older children.
AB  - INTRODUCTION: Successful bladder closure in cloacal exstrophy (CE) is best
      accomplished through a multidisciplinary team and attention to pre- and
      postoperative technique. This study from a high volume exstrophy center
      investigates outcomes and complications of primary and reoperative bladder
      closures in patients immobilized with spica cast or patients with external
      fixation (EF) and skin traction. METHODS: The authors reviewed an institutionally
      approved and daily updated database of 1311 patients with exstrophy-epispadias
      complex and identified patients with cloacal exstrophy born between 1975 and 2015
      who had undergone primary or reoperative bladder closures. Only the closures that
      used spica casting or external fixation were included for analysis. Demographic,
      operative, and outcomes data were compared between patients with spica cast only
      and patients with external fixation and skin traction. RESULTS: Out of 140
      patients with CE or a CE variant, a total of 71 patients with 94 bladder closures
      (66 primary and 28 reoperative) met inclusion criteria. Median follow-up time was
      8.8 years (range 1.5-29.1). There were 37 closures performed at the authors'
      institution and 58 from outside hospitals. Pelvic osteotomy was undertaken in 66
      (70.2%) of all closures, and in 36 (97.3%) of closures at the authors'
      institution. Postoperative immobilization was achieved with spica cast alone in
      46 (48.9%) closures, external fixation and skin traction in 43 (45.7%), and spica
      cast and external fixation in 5 (5.3%) closures. For all closures, there were 33
      failures (71.7%) among those immobilized with spica cast alone versus 4 failures
      (9.3%) for those immobilized with external fixation and skin traction (p<0.001).
      When restricted to closures performed with osteotomy, the failure rates were
      50.0% and 9.3% respectively (p=0.002). There was minimal differences in
      complication rates between spica and external fixation groups (8.7% versus 23.3%,
      p=0.059). CONCLUSION: Failure of CE closure can occur with any form of pelvic and
      lower extremity immobilization. This study, however, provides continued evidence
      that external fixation with skin traction is an optimal, secure technique (3.8%
      failure rate) for postoperative management in an older child (1-2 years). LEVEL
      OF EVIDENCE: Level III, Retrospective comparative study STUDY TYPE: Therapeutic
      study.

PMID- 29370896
TI  - Reply to Letter to the Editor.

PMID- 29370897
TI  - Letter to the Editor.

PMID- 29370898
TI  - Postoperative complications of pediatric patients with inflammatory bowel disease
      treated with vedolizumab.
AB  - BACKGROUND: Vedolizumab is a biologic, which inhibits leukocyte adhesion in the
      gut and is used to treat ulcerative colitis (UC) and Crohn's disease (CD). Little
      is known of the surgical outcomes in patients treated with vedolizumab. We
      reviewed the postoperative complications in a cohort of pediatric UC and CD
      patients treated with vedolizumab. METHODS: We identified pediatric UC and CD
      patients treated with vedolizumab at our institution from 2014 to 2016. We
      compared postoperative outcomes in the vedolizumab exposed group to a cohort of
      vedolizumab naive patients who required diverting ileostomy. RESULTS: Of the 31
      patients who were treated with vedolizumab, 13 patients required surgery. Eight
      of 13 (62%) vedolizumab exposed patients had a postoperative complication,
      including mucocutaneous separation at the stoma (3), readmission for
      pain/dehydration (2), bowel obstruction at the ostomy, and intraoperative colonic
      perforation. In comparison, four of 16 (25%) vedolizumab naive patients had a
      postoperative complication, including readmission for ileus and for high stoma
      output with mucocutaneous separation. p=0.07. CONCLUSIONS: At our institution,
      patients treated with vedolizumab prior to surgery have a high prevalence of
      postoperative complications, notably mucocutaneous separation of the stoma. A
      prospective, multicenter study is needed to determine if these observed
      complications are attributable to vedolizumab. LEVEL OF EVIDENCE: Level III.

PMID- 29370899
TI  - Reliability-based robust dynamic positioning for a turret-moored floating
      production storage and offloading vessel with unknown time-varying disturbances
      and input saturation.
AB  - In this paper, we derived a mathematical model for a floating production storage
      and offloading (FPSO) vessel and its buoy mooring system and developed a new
      robust positioning controller to keep vessels in a desired region in the presence
      of unknown time-varying disturbances with uncertainties and input saturation.
      Different materials (chain and polyester) and buoys are considered in the model
      of mooring system to make the developed model more realistic. We employed a
      disturbance observer to estimate the disturbances and designed an auxiliary
      dynamic system integrated with the structural reliability's derivative to
      quantify the input saturation's influence, and its states are used to the control
      design. Our proposed controller can keep the structural reliability and heading
      at desired values with arbitrarily small errors while guaranteeing the uniform
      ultimate boundedness of all signals in the closed-loop control system. It is
      easier for the control design because disturbances and input saturation are
      handled simultaneously and so is the stability analysis because only one Lyapunov
      function is needed. Simulations are conducted to demonstrate our proposed
      controller's effectiveness and a comparison with a robust controller based on
      hyperbolic tangent functions shows our proposed controller can avoid steady
      errors with desired control goals.

PMID- 29370900
TI  - Continuous erector spinae plane block for analgesia in pediatric thoracic
      surgery: A case report.
AB  - Erector spinae plane block has been recently described and it appears as a very
      promising regional analgesia technique. We report the first continuous erector
      spinae plane block performed in a pediatric patient for thoracic surgery. A 15
      month-old boy, diagnosed with a paracardiac teratoma was scheduled for a tumor
      resection with a thoracotomy approach. After general anesthesia induction, a
      continuous erector spinae plane block at T5 level was performed with ropivacaine
      0.2%. After surgery, a continuous thoracic interfascial infusion of ropivacaine
      0.1% along with multimodal rescue analgesia was initiated. The patient tolerated
      the procedure well with no complications. It appears that this is a good
      alternative to thoracic epidural and paravertebral block, given the simple
      reproducibility and potential greater safety of this technique.

PMID- 29370901
TI  - Massive right hemothorax due to idiopathic spontaneous rupture of a phrenic
      artery following cardiac surgery.
AB  - We report a case of a 35-years-old man who presented a massive haemothorax and
      hypovolemic shock following cardiac surgery, from spontaneous rupture of a
      phrenic artery. A quick diagnosis and immediate intervention is crucial to manage
      the patient.

PMID- 29370902
TI  - Opioid free anesthesia with BIS/EMG monitored propofol-ketamine.

PMID- 29370903
TI  - LKB1 inactivation occurs in a subset of esophageal adenocarcinomas and is
      sufficient to drive tumor cell proliferation.
AB  - BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) has increased over
      the last several decades. Apart from mutations in TP53 gene, there are little
      data on genetic drivers of EAC. Liver kinase B1 (LKB1) has emerged as a
      multifunctional tumor suppressor regulating cell growth, differentiation, and
      metabolism. Somatic inactivation of LKB1 has been described in several tumor
      types; however, whether LKB1 inactivation has a role in EAC is unknown. Here we
      analyzed patient tumors to assess the prevalence of LKB1 loss in EAC. METHODS:
      Chromosomal deletion and expression of LKB1 in EAC were investigated using
      publicly available genomic data. Protein expression was assessed by
      immunohistochemistry (IHC) analysis for LKB1 in a tissue microarray (TMA)
      containing esophageal tumor specimens, including EAC. LKB1 was suppressed in EAC
      cells to determine the effects on cell growth in vitro. RESULTS: Analysis of EAC
      data in The Cancer Genome Atlas dataset revealed significant deletion of
      chromosome 19p13.3, containing the LKB1 gene locus. Single copy loss (shallow
      deletion) of LKB1 was present in 58% of EAC samples. Expression of LKB1 was
      significantly lower in EAC tumors compared with normal esophagus. IHC analysis
      showed reduced LKB1 protein expression in EAC. Suppression of LKB1 was sufficient
      to enhance EAC cell growth in vitro. CONCLUSIONS: Our data suggest that
      inactivation of LKB1 frequently occurs in EAC. Based on the reported oncogenic
      effects of LKB1 inactivation, our data indicate that LKB1 loss may play a
      significant role in EAC tumorigenesis, and point to the need for future studies.

PMID- 29370904
TI  - Leads leading leaflets to leak.

PMID- 29370906
TI  - Do radiopaque markers make a difference after coronary artery bypass grafting?

PMID- 29370905
TI  - Right ventricular involution: What can we learn from nature's model of
      compensated hypertrophy?
AB  - BACKGROUND: Right ventricular (RV) failure (RVF) is a vexing problem facing
      patients with various disease processes and carries a high mortality. RVF is a
      poorly understood phenomenon with limited treatment options. In mammalian fetal
      circulation, the right ventricle is the systemic ventricle. In neonates, however,
      the left ventricle assumes that role and gradually thickens compared with the
      right ventricle. This process, known as right ventricular involution (RVI), is
      poorly understood. We sought to define the time course and identify mechanisms
      involved in RVI. METHODS: Wild-type mice were bred and sacrificed on day of life
      (DOL) 1, 4, 8, 16, and 30 to evaluate left ventricular (LV) and RV wall thickness
      and apoptosis. A terminal deoxynucleotidyl transferase nick-end labeling assay
      and RNA sequencing were performed to measure changes during RVI. RESULTS:
      Morphometric analysis demonstrated the changes in RV and LV wall thickness
      occurring between DOL 1 and DOL 16 (RV:LV, 0.53:0.44; P = .03). In addition,
      apoptosis was most active early, with the highest percentage of apoptotic cells
      on DOL 1 (1.0%) and a significant decrease by DOL 30 (0.23%) (P = .02).
      Similarly, expression of the proapoptotic genes BCL2l11 and Pawr were increased
      at DOL 1, and the antiapoptotic genes Nol3 and Naip2 were significantly increased
      at DOL 30. CONCLUSIONS: RVI is a misnomer, but significant changes occur early
      (by DOL 16) in neonatal mouse hearts. Apoptosis plays a role in RVI, but whether
      manipulation of apoptotic pathways can prevent or reverse RVI is unknown and
      warrants further investigation.

PMID- 29370907
TI  - Developing a robotic mitral program: What's past is prologue.

PMID- 29370908
TI  - Reconstructive aortic valve surgery in the elderly: Another example of better
      being the enemy of good?

PMID- 29370909
TI  - No need to tailor: Paraplegia risk is intrinsic to complex aortic intervention.

PMID- 29370910
TI  - Nomogram: An analogue tool to deliver digital knowledge.

PMID- 29370911
TI  - Surgical site infections after coronary artery bypass grafting-Does "never"
      really mean "never"?

PMID- 29370912
TI  - Norwood valved Sano shunt: Early reward versus late penalty?

PMID- 29370913
TI  - Hypoplastic left heart syndrome and the allure of a valved conduit.

PMID- 29370914
TI  - Management of type Ia endoleak: Back to the future?

PMID- 29370915
TI  - Is it about time to forget about intravascular lead?

PMID- 29370916
TI  - Valve-sparing aortic root replacement and the bicuspid aortic valve: The details
      matter.

PMID- 29370917
TI  - Are minimum volume standards appropriate for lung and esophageal surgery?
AB  - BACKGROUND: Several medical systems have adopted minimum volume standards for
      surgical procedures, including lung and esophageal resection. We sought to
      determine whether these proposed hospital cutoffs are associated with differences
      in outcomes. METHODS: Analyzing the State Inpatient Databases and Healthcare Cost
      and Utilization Project of the Agency for Healthcare Research and Quality, we
      evaluated all patients (aged >= 18 years) who underwent lobectomy/pneumonectomy
      or esophagectomy for cancer in California, Florida, and New York (2009-2011).
      Hospitals were defined as low volume for each procedure per proposed minimum
      volume standards by year: <40 lung resections and <20 esophagectomies. We
      compared demographic data and determined the incidence of complications and
      mortality between patients operated on at low- versus high-volume hospitals.
      Propensity matching (of demographic characteristics, income, payer, and
      comorbidities) was performed to balance the cohorts for analysis. RESULTS: During
      the time period, 20,138 patients underwent lobectomy/pneumonectomy of which
      12,432 operations (61.7%) were performed at low-volume hospitals (n = 456) and
      7706 operations were performed at high-volume hospitals (n = 48). Of 1324
      patients undergoing esophagectomy, 1087 operations (82.1%) were performed at low
      volume hospitals (n = 184), whereas only 237 operations were at high-volume
      hospitals (n = 6). After propensity matching (lung 1:1 and esophagus 2:1), no
      major differences were apparent for in-hospital mortality nor major complications
      for either lung or esophageal resection. Length of stay was longer in low-volume
      hospitals after lung resection (median 6 vs 5 days; P < .001), but not after
      esophageal resection. DISCUSSION: Although several groups have publicly called
      for minimum volume requirements for surgical procedures, the majority of patients
      undergo lung and esophageal resection at hospitals below the proposed cutoffs.
      The proposed standards for lung and esophageal resection are not associated with
      a difference in outcomes in this large administrative database. Efforts should be
      made to determine more meaningful minimum volume requirements and to determine
      whether such standards are appropriate.

PMID- 29370918
TI  - Preparation of perfusive chromatographic materials via shear-induced reactive
      gelation.
AB  - A simple method for producing highly porous materials suitable for
      chromatographic applications is discussed. Starting from a dispersion of polymer
      core-shell nanoparticles (latex), micrometer sized clusters (100 MUm) are
      produced via shear-induced Reactive Gelation. Thanks to their fractal structure,
      these aggregates exhibit highly porous structures, with pore size distribution
      ranging from 0.1 to several micrometers. The effect of different properties of
      the primary nanoparticles on the qualities of the final products is also
      investigated. Particle architecture, namely the ratio between the hard, highly
      crosslinked core, and the soft, poorly crosslinked shell, turned out to be the
      most important parameter to be tuned in order to obtain highly porous and
      mechanically resistant clusters. The final materials can be easily slurry-packed
      into conventional chromatographic columns. In comparison to other commercial
      stationary phases, these materials show not only much lower pressure drops at
      very high flow rates (i.e. <0.2 bar/cm at 6 mL/min), but also HETP profiles
      independent of fluid velocity when measured with tracers of sizes comparable to
      typical bio-macromolecules. Moreover, these materials, while offering the key
      advantage of being in a slurry form and thus easily packable and scalable, have a
      behavior that closely resembles that of monoliths, in which convective flow
      contribution dominates.

PMID- 29370919
TI  - Simultaneous quantification of epoxy and hydroxy fatty acids as oxidation
      products of triacylglycerols in edible oils.
AB  - Epoxy and hydroxy fatty acids are important intermediates during lipid oxidation;
      quantification of both structures may help evaluate the extent of competition
      among various lipid oxidation pathways. This article describes a method to
      simultaneously determine saturated- and unsaturated- epoxy and hydroxy fatty
      acids derived from oxidation of vegetable oils. The experimental procedures
      employed transesterification with sodium methoxide, separation of epoxy and
      hydroxy fatty acid methyl esters (FAME) using solid-phase extraction (SPE), and
      trimethylsilyl (TMS) derivatization of hydroxy groups. GC-MS was used to identify
      the epoxy and hydroxy FAME in two different SPE fractions, while GC-flame
      ionization detection (GC-FID) was used to determine their quantities. Epoxy
      octadecanoate/octadecenoate and hydroxy
      octadecanoate/octadecenoate/octadecadienoate were determined as lipid oxidation
      products generated from oxidation of sunflower and canola oils. An isomer of
      methyl 13-hydroxyoctadeca-9,11-dienoate (13-HODE) TMS ether co-eluted with methyl
      15-hydroxyoctadeca-9,12-dienoate TMS ether, which was only present in canola oil;
      thus, GC-MS-selected ion monitoring (GC-MS-SIM) was used to determine the
      concentration of 13-HODE. The proposed method has been successfully applied to
      monitor epoxy and hydroxy fatty acids in sunflower oil and canola oil oxidized at
      40  degrees C.

PMID- 29370920
TI  - Use of counter-current chromatography as a selective extractor for the
      diterpenequinone 7alpha-hydroxyroyleanone from Tetradenia riparia.
AB  - A solvent system was developed for selective isolation by high-speed counter
      current chromatography (HSCCC) of the benzoquinone 7alpha-hydroxyroileanone, 1, a
      bioactive diterpene from a dichloromethane extract of Tetradenia riparia leaves.
      Several solvent systems were initially studied, including hexane-ethyl acetate
      methanol-water in several ratios, hexane-acetone-methanol-water, hexane-ethanol
      water and hexane-acetonitrile-methanol, which gave recovery rates for the target
      compound between 13.4 and 35.9%. The new solvent system hexane-5% aqueous Na2CO3
      (1:1) was developed based on the chemical ionization reaction of the benzoquinone
      hydroxyl group in the basic pH of the carbonate solution, prompted by the
      extraction procedure used for the extraction of lapachol (a natural
      naphtoquinone) from a Tabebuia species wood. By using the HSCCC chromatograph as
      a liquid-liquid extractor with the above mentioned solvent system the recovery
      rate of 1 increased to 81.8%, affording the quinone with 97% purity.

PMID- 29370921
TI  - Multilayer affinity adsorption of albumin on polymer brushes modified membranes
      in a continuous-flow system.
AB  - Polymer brushes modified surfaces have been widely used for protein
      immobilization and isolation. Modification of membranes with polymer brushes
      increases the surface concentration of affinity ligands used for protein binding.
      Albumin is one of the transporting proteins and shows a high affinity to bile
      acids. In this work, the modified membranes with cholic acid-containing polymer
      brushes can be facilely prepared by the immobilization of cholic acid on the
      poly(2-hydroxyethyl methacrylate) grafted microporous polypropylene membranes
      (MPPMs) for affinity adsorption of albumin. ATR/FT-IR and X-ray photoelectron
      spectroscopy were used to characterize the chemical composition of the modified
      membranes. Water contact angle measurements were used to analyze the
      hydrophilic/hydrophobic properties of the membrane surface. The modified MPPMs
      show a high affinity to albumin and have little non-specific adsorption of
      hemoglobin. The dynamic binding capacity of albumin in the continous-flow system
      increases with the cycle number and feed rate as the binding degree of cholic
      acid is moderate. The highest binding capacity of affinity membranes is about
      52.49 g/m2 membrane, which is about 24 times more than the monolayer binding
      capacity. These results reveal proteins could be captured in multilayers by the
      polymer brushes containing affinity ligands similar to the polymer brushes
      containing ion-exchange groups, which open up the potential of the polymer
      brushes containing affinity ligands in protein or another components separation.
      And the cholic acid containing polymer brushes modified membranes has the
      promising potential for albumin separation and purification rapidly from serum or
      fermented solution in medical diagnosis and bioseparation.

PMID- 29370922
TI  - Incidence and Prognosis of Pericarditis After ST-Elevation Myocardial Infarction
      (from the Acute Coronary Syndrome Israeli Survey 2000 to 2013 Registry Database).
AB  - There are scarce contemporary data regarding the incidence and prognosis of early
      postmyocardial infarction pericarditis (PMIP). Thus, we retrospectively analyzed
      6,282 patients with ST-segment elevation myocardial infarction (STEMI) enrolled
      with known PMIP status in the Acute Coronary Syndrome Israeli Survey 2000 to 2013
      registry. The primary outcome was the composite of all-cause mortality, nonfatal
      myocardial infarction, cerebrovascular event, stent thrombosis, or
      revascularization. The secondary outcomes were mortality and length of stay
      during the acute hospitalization. Overall, 76 patients with STEMI had PMIP
      (1.2%). PMIP incidence gradually decreased from 170 per 10,000 in 2000 to 110 per
      10,000 in 2013, respectively (35% reduction, p for trend = 0.035). Patients with
      PMIP were younger (median 58.0 vs 61.0; p = 0.045), had less hypertension, higher
      cardiac biomarkers, and more frequently reduced left ventricular ejection
      fraction (87.0% vs 67.0%; p = 0.001). Patients with PMIP had longer time to
      reperfusion (225 minutes vs 183 minutes; p = 0.016) and length of stay (7.0 vs
      5.0 days; p < 0.001). The composite end point occurred similarly in patients with
      and without PMIP (10.5% vs 13.2%, respectively). There was no significant
      difference in 30-day, 1-year, and 5-year survival. In conclusion, PMIP is a
      relatively rare complication of STEMI in the coronary reperfusion era, portends
      worse short-term but not long-term outcomes, and is associated with bigger
      infarct size.

PMID- 29370923
TI  - The Role of Mechanical Circulatory Support During Percutaneous Coronary
      Intervention in Patients Without Severely Depressed Left Ventricular Function.
AB  - Currently, there are no data on the use of mechanical circulatory support (MCS)
      in patients without severely depressed left ventricular ejection fraction (LVEF)
      during high-risk percutaneous coronary intervention (PCI). We analyzed data from
      the global catheter-based ventricular assist device (cVAD) registry on the
      clinical use of MCS in high-risk PCI in patients without severely depressed LVEF,
      defined as LVEF > 35%. Patients without cardiogenic shock from the catheter-based
      ventricular assist device registry, who underwent elective or urgent PCI with an
      Impella 2.5 or Impella CP, were included. Patients who received MCS after the
      start of the PCI were excluded. A total of 891 patients were included, of whom
      661 had LVEF <= 35% and 230 had LVEF > 35%. Patients with LVEF > 35% compared
      with patients with LVEF <= 35% were older (72.12 +/- 11.70 years vs 68.68 +/-
      11.01 years; p <0.001), had more extensive coronary artery disease with more
      diseased vessels (1.90 +/- 0.71 vs 1.73 +/- 0.79; p = 0.005), more multivessel
      intervention (1.74 +/- 0.69 vs 1.55 +/- 0.73; p <0.001), and more use of
      rotational atherectomy (21.21% vs 14.90%; p = 0.046), respectively. Additionally,
      they had a high prevalence of high-risk clinical features such as renal failure
      (24.89%) and diabetes mellitus (45.37%). Despite these high-risk features, the
      major adverse cardiovascular and cerebral event rates were favorable overall,
      with no differences between the 2 groups (3.48% vs 4.54%; p = 0.574). Despite
      having LVEF > 35%, this selected group of patients had severe co-morbidities and
      complex angiographic features; hence, PCI with hemodynamic support was deemed
      necessary. In addition, PCI with elective MCS was feasible and safe in this
      patient population.

PMID- 29370924
TI  - Comparison of Survival After In-Hospital Cardiac Arrest in Patients With Versus
      Without Diabetes Mellitus.
AB  - Diabetes mellitus (DM) increases the risk of sudden cardiac death, but the extent
      to which it influences survival after an in-hospital cardiac arrest (IHCA)
      remains unclear. We assessed the association of DM and survival after IHCA. The
      study included 1,009,073 patients aged >=18 years who underwent cardiopulmonary
      resuscitation for IHCA between January 2003 and December 2013, recorded in the
      Nationwide Inpatient Sample database. The outcomes were survival to hospital
      discharge and discharge disposition assessed using multivariable logistic
      regression accounting for relevant covariates and clustering. Of the patients
      with IHCA, 30.8% (310,825) had DM and were more likely to be older and to have a
      higher prevalence of co-morbidities including hypertension, dyslipidemia, chronic
      kidney disease, and previous cardiovascular disease (all p <0.001). The rates of
      survival to hospital discharge after IHCA were 27.0% and 25.1% in patients with
      and without DM, respectively. After multivariable adjustment, DM was associated
      with a modestly lower risk-adjusted survival to hospital discharge (adjusted OR
      [aOR] 0.96, 95% confidence interval [95% CI] 0.95 to 0.97, p <0.001). This
      association was influenced by a number of factors (all interaction p <0.001),
      including a lower risk of survival among patients with DM who were younger (aOR
      0.93, 95% CI 0.92 to 0.94 among those aged <75 years), those with a primary
      cardiovascular diagnosis (aOR 0.88, 95% CI 0.86 to 0.89), and those with
      ventricular fibrillation/ventricular tachycardia as the cardiac arrest rhythm
      (aOR 0.88, 95% CI 0.79 to 0.82). Patients with DM had lower odds of being
      discharged home with self-care after surviving an IHCA (p <0.001). In conclusion,
      preexisting DM was associated with a modestly lower risk-adjusted chance of
      survival after an IHCA.

PMID- 29370925
TI  - Reply.

PMID- 29370926
TI  - Disparities in managing emotions when facing a diagnosis of breast cancer:
      Results of screening program of couples distress.
AB  - INTRODUCTION: Distress screening is now required for cancer center accreditation.
      Understanding patient and caregiver stress is critical to successful cancer care.
      This study examines the perceived emotional impact of breast cancer on both
      patients and partners. METHODS: From March 2011-February 2016, patients and
      partners undertook an electronic, 48-point distress screen during their first
      visit at a surgical breast clinic. Distress was measured via self-reported
      concerns on a five point Likert scale. Respondents were also asked about
      preferred interventions. The ability of the patient and partner to manage
      emotions was assessed in relation to education, ethnicity, fatigue, anxiety, and
      depression using ordered logistic regression. RESULTS: Of the 665 individuals
      screened, 51.7%(n = 344) were patients, while 48.3%(n = 321) were partners.
      Patients were more distressed than partners regarding fatigue, anxiety,
      depression, and worrying about the future (p < 0.005). Only 19.7% of partners
      requested information with regards to "managing emotions" compared to 46.3% of
      patients. In the univariate analysis, being a partner was protective (OR 0.49
      (95%CI 0.34-0.70, p < 0.000) as was holding an advanced educational degree (OR
      0.36 (95%CI 0.14-0.93) p = 0.035). In the multivariate regression, having more
      education remained protective, while being a partner was no longer protective (OR
      0.93(95%CI 0.62-1.39, p = 0.789). Financial concerns, anxiety, depression, and
      worrying about the future remained statistically significant. Partners asked for
      help less than patients (OR 0.28 (95%CI 0.17-0.48), p < 0.000). CONCLUSION: While
      partners have similar concerns as patients, they do not seek information or help
      in managing emotions as often as do patients. Both patient and partners with less
      education and increased financial distress were likely to report difficulty in
      managing emotions. This study identifies groups who would benefit from supportive
      measures even in the absence of a request for help.

PMID- 29370927
TI  - Racial and regional disparity in liver transplant allocation.
AB  - BACKGROUND: Sources of liver transplant disparities are not understood
      adequately, particularly in terms of race and region. METHODS: Fixed effects
      multivariate logistic regression augmented by modified forward and backward
      stepwise regression of transplanted patients from the United Network for Organ
      Sharing Standard Transplant Analysis and Research database (1985-2016) was
      performed to assess causal inference of such disparities. RESULTS: In the study
      sample (N = 258,602), significant disparities in the odds of receiving a liver
      were found: African Americans odds ratio 1.12 (95% confidence interval, 1.08
      1.17), Asians 1.12 (95% confidence interval, 1.07-1.18), females 0.80 (95%
      confidence interval, 0.78-0.83), and malignancy 1.18 (95% confidence interval,
      1.13-1.22). Region 7 (IL, MN, ND, SD, and WI) was set as the reference level
      since its transplantation rate most closely approximated the sex and race-matched
      rate of the national post-Share 35 average. Significant racial disparities by
      region were identified using Caucasian Region 7 as the reference: Hispanic Region
      9 (New York, West Vermont) 1.22 (1.02-1.45), Hispanic Region 1 (New England) 1.26
      (1.01-1.57), Hispanic Region 4 (Oklahoma, TX) 1.23 (1.05-1.43), and Asian Region
      4 (Oklahoma, TX) 1.35 (1.05-1.73). CONCLUSION: Despite numerous adjustments to
      liver allocation, we identified with causal inference statistics on a large
      dataset spanning >=30 years there remain racial and regional overweighting.

PMID- 29370928
TI  - Discussion.

PMID- 29370929
TI  - Liver transplant offers a survival benefit over margin negative resection in
      patients with small unifocal hepatocellular carcinoma and preserved liver
      function.
AB  - BACKGROUND: Studies comparing orthotopic liver transplantation to margin negative
      resection for patients with small unifocal hepatocellular carcinoma have not
      controlled for degree of cirrhosis. METHODS: The National Cancer Database was
      used to identify patients with preserved liver function (Model for End-stage
      Liver Disease score <=12) who underwent orthotopic liver transplantation or
      margin negative resection for American Joint Committee on Cancer stage I
      hepatocellular carcinoma lesions <3 cm between 2010 and 2013. Multivariable and
      Cox regression adjusting for age, demographics, comorbid disease burden, Model
      for End-stage Liver Disease score, tumor size, and operation were used to compare
      overall survival between cohorts. RESULTS: In the study, 241 (53%) patients
      underwent orthotopic liver transplantation. In addition, 219 (47%) underwent
      margin negative resection. On multivariable regression, patients having a
      Charlson comorbidity score >=2 were more likely to undergo orthotopic liver
      transplantation, (odds ratio 1.94, P=.03). African American patients (odds ratio
      0.44, P=.02), and patients of advanced age (odds ratio 0.92, P<.001) were more
      likely to undergo margin negative resection. Patients undergoing orthotopic liver
      transplantation had longer overall survival than those undergoing margin negative
      resection (median OS not reached versus 67.6 months, P<.001). Multivariable Cox
      regression identified surgical procedure as the only independent determinant of
      survival with margin negative resection conferring a nearly 3-fold increased risk
      of death (hazard ratio 2.86, P<.001). CONCLUSION: Orthotopic liver
      transplantation offers a survival advantage relative to margin negative resection
      for patients with small unifocal hepatocellular carcinoma and preserved liver
      function.

PMID- 29370931
TI  - Discussion.

PMID- 29370930
TI  - Expression of phosphorylated sphingosine kinase 1 is associated with diffuse type
      and lymphatic invasion in human gastric cancer.
AB  - BACKGROUND: Sphingosine-1-phosphate, a pleiotropic bioactive lipid mediator, is
      an important player in cancer progression. Previous studies suggested that
      sphingosine-1-phosphate produced by sphingosine kinase 1, which is activated by
      phosphorylation, plays important roles in the progression of disease and
      metastasis. The association between phospho-sphingosine-1-phosphate produced by
      sphingosine kinase 1 and clinical parameters in human gastric cancer have not
      been fully investigated to date. METHODS: We created phospho-sphingosine-1
      phosphate produced by sphingosine kinase expression profiles by
      immunohistochemistry for 136 patients who underwent operative intervention for
      gastric cancer in 2007-2009. Phospho-sphingosine-1-phosphate produced by
      sphingosine kinase expression and compared clinicopathologic factors by
      univariate and multivariate analyses. RESULTS: The univariate analysis revealed
      that phospho-sphingosine-1-phosphate produced by sphingosine kinase expression
      was correlated significantly with depth of tumor invasion, lymph node metastasis,
      distant metastasis, histologic type, and lymphatic invasion. The multivariate
      analysis revealed that the diffuse type (odds ratio 2.210; 95% confidence
      interval, 1.045-4.671, P=.038) and the presence of lymphatic invasion (odds ratio
      3.697; 95% confidence interval, 1.161-8.483, P=.002) were associated
      independently with phospho-sphingosine-1-phosphate produced by sphingosine kinase
      expression in patients with gastric cancer. The 5-year rate of disease-specific
      survival was 79.3% in patients with phospho-sphingosine-1-phosphate produced by
      sphingosine kinasephospho-sphingosine-1-phosphate produced by sphingosine kinase
      positive expression and 98.3% in those with phospho-sphingosine-1-phosphate
      produced by sphingosine kinase-negative expression (P=.002). In multivariate
      analysis, however, high phospho-sphingosine-1-phosphate produced by sphingosine
      kinase expression was not an independent prognostic factor for disease-specific
      survival (hazard ratio 5.540; 95% confidence interval, 0.717-42.81, P=.100).
      CONCLUSION: We provide the first evidence that diffuse histologic type and
      lymphatic invasion were independently associated with high phospho-sphingosine-1
      phosphate produced by sphingosine kinase expression in gastric cancer patients,
      indicating a role of sphingosine-1-phosphate in disease progression among
      patients with gastric cancer. (Surgery 2017;160:XXX-XXX.).

PMID- 29370932
TI  - Lifetime and Aging of Chromatography Resins during Biopharmaceutical Manufacture.
AB  - Poor understanding of the events leading to chromatography column aging makes it
      difficult to monitor column lifetimes. The lack of established procedures in this
      area has made it difficult to establish industry standards. Therefore, it is
      important to understand resin aging mechanisms and techniques to monitor column
      aging during operation.

PMID- 29370933
TI  - Assessment of the charlson comorbidity index score, CHADS2 and CHA2DS2-VASc
      scores in predicting death in patients with thoracic empyema.
AB  - BACKGROUND: Patients with thoracic empyema have an increased risk of mortality,
      but their absolute rate of mortality depends on age and comorbidities. OBJECTIVE:
      This study seeks to assess the predictive value of the Charlson Comorbidity Index
      score (CCIS), CHADS2 and CHA2DS2-VASc scores for mortality risk in patients with
      empyema thoracis. METHODS: From Taiwan's National Health Insurance Research
      Database we identified a total of 484 participants diagnosed with thoracic
      empyema. The CCIS, CHADS2 and CHA2DS2-VASc scores were used to stratify mortality
      risk. RESULTS: The incidence rate of mortality in the present study was 20.39 per
      1000 person-months. A strong correlation was found between thoracic empyema and
      CCIS score. CONCLUSIONS: Our results show that patients with thoracic empyema
      have a significantly high incidence rate of mortality and that CCIS can be used
      as an indicator of risk for mortality.

PMID- 29370934
TI  - Mutation analysis of the TIA1 gene in Chinese patients with amyotrophic lateral
      sclerosis and frontotemporal dementia.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by the progressive loss of motor neurons in the brain and spinal
      cord. Frontotemporal dementia (FTD) is a group of dementia syndromes
      characterized by the progressive deterioration of behaviors, executive
      dysfunction, and verbal impairment. Increasing evidence indicates that these 2
      diseases share a common genetic etiology and pathophysiological mechanism.
      Recently, rare mutations in the low-complexity domain of the RNA-binding protein
      T-cell-restricted intracellular antigen-1 (TIA1) gene were identified in
      Caucasian ALS and ALS-FTD patients. However, no comprehensive mutation analysis
      of the TIA1 gene has been performed in Chinese patients with ALS and FTD. In this
      study, we screened the low-complexity domain of TIA1 in a cohort of 241 ALS and
      51 FTD patients in mainland China. As a result, 2 novel missense mutations
      (p.P352L and p.I300T) were identified in 2 sporadic patients with ALS, while no
      mutation was found in FTD cases. To the best of our knowledge, this report
      presented the first mutation analysis of the TIA1 gene in patients with ALS and
      FTD in Chinese population. Our findings broaden the known mutational spectrum in
      patients with ALS and further confirm TIA1 as a novel causative gene of ALS.

PMID- 29370935
TI  - Short-term variability of fish condition and growth in estuarine and shallow
      coastal areas.
AB  - Short-term variability in condition factor: relative condition factor Kn;
      biochemical condition: RNA:DNA and protein content; and instantaneous growth
      rates were determined in estuarine and coastal fish. Dicentrarchus labrax, Solea
      senegalensis and Pomatoschistus microps were sampled in the Tejo estuary, while
      Trachurus trachurus was sampled in an adjacent shallow coastal area. Variation of
      condition indices was more frequent at the week scale (sampling periods with
      fortnight intervals) than at the daily scale (consecutive days in each sampling
      period) in all species. Water temperature was correlated with biochemical
      indices, while salinity showed no effect, evidencing the influence of
      environmental short-term variation (temperature) on biochemical condition in
      natural populations. Yet, decreasing individual variability in fish condition was
      observed along the sampled weeks, resulting in a more homogeneous condition of
      populations, particularly for T. trachurus likely due to a more stable coastal
      environment. Biochemical indices proved to be sensitive to short-term
      environmental variability, despite species-specific responses.

PMID- 29370936
TI  - Black guillemot ecology in relation to tidal stream energy generation: An
      evaluation of current knowledge and information gaps.
AB  - The black guillemot Cepphus grylle has been identified as a species likely to
      interact with marine renewable energy devices, specifically tidal turbines, with
      the potential to experience negative impacts. This likelihood is primarily based
      on the species being a diving seabird, and an inshore, benthic forager often
      associating with tidal streams. These behavioural properties may bring them into
      contact with turbine blades, or make them susceptible to alterations to tidal
      current speed, and/or changes in benthic habitat structure. We examine the
      knowledge currently available to assess the potential impacts of tidal stream
      turbines on black guillemot ecology, highlight knowledge gaps and make
      recommendations for future research. The key ecological aspects investigated
      include: foraging movements, diving behaviour, seasonal distribution, other
      sources of disturbance and colony recovery. Relating to foraging behaviour,
      between studies there is heterogeneity in black guillemot habitat use in relation
      to season, tide, diurnal cycles, and bathymetry. Currently, there is also little
      knowledge regarding the benthic habitats associated with foraging. With respect
      to diving behaviour, there is currently no available research regarding how black
      guillemots orientate and manoeuvre within the water column. Black guillemots are
      considered to be a non-migratory species, however little is known about their
      winter foraging range and habitat. The effect of human disturbance on breeding
      habitat and the metapopulation responses to potential mortalities are unknown. It
      is clear further understanding of black guillemot foraging habitat and behaviour
      is needed to provide renewable energy developers with the knowledge to
      sustainably locate tidal turbines and mitigate their impacts.

PMID- 29370937
TI  - [Public health interventions against hate violence].

PMID- 29370938
TI  - NaV1.7 as a Pharmacogenomic Target for Pain: Moving Toward Precision Medicine.
AB  - Chronic pain is a global unmet medical need. Most existing treatments are only
      partially effective or have side effects that limit their use. Rapid progress in
      elucidating the contribution of specific genes, including those that encode
      peripheral voltage-gated sodium channels, to the pathobiology of chronic pain
      suggests that it may be possible to advance pain pharmacotherapy. Focusing on
      voltage-gated sodium channel NaV1.7 as an example, this article reviews recent
      progress in developing patient-specific induced pluripotent stem cells (iPSCs)
      and their differentiation into sensory neurons, together with advances in
      structural modeling, that have provided a basis for first-in-human translational
      studies. These new approaches will hopefully transform the treatment of pain from
      trial-and-error toward genomically guided, precision pharmacotherapy.

PMID- 29370939
TI  - Knowledge needed about the exchange physiology of the placenta.
AB  - There is now a basic understanding of the driving forces and mechanisms
      underlying rates of solute exchange across the placenta but there are still major
      gaps in knowledge. Here we summarise this basic understanding, whilst
      highlighting gaps in knowledge. We then focus on two particular areas where more
      knowledge is needed: (1) the electrical potential difference (PD) across the
      placenta and (2) the paracellular permeability of the placenta to hydrophilic
      solutes. In many species a PD has been recorded between a catheter in a maternal
      blood vessel and one in a fetal vessel. However, the key question is whether this
      PD is the same as that across the placental exchange barrier. We addressed this
      in the human placenta using microelectrodes to measure the PD in isolated villi
      in vitro; the transtrophoblast PD so measured had a median value of -3 mV (range
      0-15 mV). There have been no subsequent studies to validate this measurement. The
      syncytiotrophoblast of haemochorial placentas lacks any obvious extracellular
      water filled paracellular space between the syncytial nuclei. However, in mouse,
      rat, guinea pig and human there is an inverse relationship between the rate of
      diffusion of inert hydrophilic solutes across the placenta and their molecular
      size. The simplest explanation is that a paracellular route exists but its
      morphological identity is still uncertain. Areas of syncytial denudation could
      provide a paracellular route but this has not been proven. Answers to these and
      similar questions are required to fully understand the exchange physiology of the
      normal placenta and how this is affected in pathology.

PMID- 29370940
TI  - Corrigendum to "Identification of potential early biomarkers of preeclampsia"
      [Placenta (2018) 61-71].

PMID- 29370941
TI  - Has the risk of mortality related to short-term exposure to particles changed
      over the past years in Athens, Greece?
AB  - Although the health effects of short-term exposure to ambient particles have been
      well documented, there is a need to update scientific knowledge due to the
      continuously changing profile of the air pollution mixture. Furthermore the
      effect of the severe economic crisis in Greece that started in 2008 on previously
      reported associations has not been studied. We assessed the change in mortality
      risk associated with short-term exposure to PM10 in Athens, Greece during 2001
      12. Time-series data on the daily concentrations of regulated particles and all
      cause, cardiovascular and respiratory mortality were analyzed using overdispersed
      Poisson regression models, controlling for time-varying confounders such as
      seasonality, meteorology, influenza outbreaks, summer holidays and day of the
      week. We assessed changes in risk over time by inclusion of an interaction term
      between particles' levels and time or predefined periods, i.e. 2001-07 and 2008
      12. While the related mortality risks increased over the analyzed period, the
      difference before and after 2008 was significant only for total mortality (p
      value for interaction .03) and driven by the difference observed among those >=75
      years. An interquartile increase in PM10 before 2008 was associated with 1.51%
      increase in deaths among >=75 years (95% Confidence interval (CI): 0.62%, 2.40%),
      while after 2008 with a 2.61% increase (95%CI: 1.72%, 3.51%) (p-value for
      interaction .01). Our results indicate that despite the decline in particles'
      concentration in Athens, Greece during 2001-12 the associated mortality risk has
      possibly increased, suggesting that the economic crisis initiated in 2008 may
      have led to changes in the particles' composition due to the ageing of the
      vehicular fleet and the increase in the use of biomass fuel for heating.

PMID- 29370942
TI  - Maintaining Apical Patency Does Not Increase Postoperative Pain in Molars with
      Necrotic Pulp and Apical Periodontitis: A Randomized Controlled Trial.
AB  - INTRODUCTION: This prospective, single-center, single-blind, randomized
      controlled trial aimed to evaluate whether maintaining apical patency (AP) during
      endodontic treatment increases postoperative pain in molar teeth with necrotic
      pulp and apical periodontitis. METHODS: Three hundred twenty qualified patients
      between 21 and 45 years of age were randomized into 1 of 2 groups (the AP group
      and the nonapical patency [NAP] group) using a series of random numbers in a 1:1
      ratio. Qualified patients were selected from patients who had necrotic pulp and
      apical periodontitis in the maxillary or mandibular molar teeth. The primary
      outcome was to assess postoperative pain severity, and the secondary outcome was
      to evaluate analgesic consumption during the 7-day follow-up period using the
      visual analog scale (VAS). The VAS consisted of a 100-mm line. Pain severity was
      evaluated as no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and
      severe pain (75-100 mm). The Student t test was used to identify statistically
      significant differences between the study groups (P < .05). RESULTS: The mean VAS
      scores were significantly lower in the AP group in the first 5 postoperative days
      (P < .05); after which, it was nonsignificant. In the NAP group, the
      postoperative pain increased between 12 and 24 hours, whereas the postoperative
      pain decreased in the AP group during that period. At 12 and 24 hours, the mean
      VAS scores for the AP group were 42.90 and 37.78 mm, respectively. The mean VAS
      scores for the NAP group were 64.46 and 65.74 mm, respectively. None of the
      patients had severe postoperative pain during the follow-up period. No
      significant difference was found in analgesic consumption (P > .05) between the
      groups. CONCLUSIONS: The maintenance of AP in molar teeth with necrotic pulp and
      apical periodontitis was associated with less postoperative pain when compared
      with NAP.

PMID- 29370943
TI  - Evaluation of the Biodistribution of Human Dental Pulp Stem Cells Transplanted
      into Mice.
AB  - INTRODUCTION: Several studies have attempted to use human dental pulp stem cells
      (hDPSCs) for pulp-dentin complex regeneration in vitro. However, the safety of
      such applications should be first evaluated in vivo before their use in clinical
      trials. The purpose of this study was to investigate the in vivo fate of
      intrapulpally transplanted hDPSCs. METHODS: hDPSCs were isolated and cultured
      from impacted third molars. In vivo experiments were performed using 7-week-old
      male BALB/c nude mice. Under deep anesthesia, 1 * 105 hDPSCs were transplanted in
      mice via the tail vein for intravenous injection or into the pulp chamber for
      intrapulpal transplantation. A total of 56 mice, 28 per group, were used. Mice
      were sacrificed at different time points, and the numbers of hDPSCs in the organs
      were analyzed quantitatively. In addition, qualitative analysis was performed to
      detect intrapulpally transplanted hDPSCs. RESULTS: Intravenously injected hDPSCs
      were mostly distributed to the lungs and rarely detected in other organs at all
      observed time points. The hDPSCs transplanted into the pulp chamber rarely
      migrated to other organs over time. CONCLUSIONS: These data indicate a
      differential distribution of transplanted hDPSCs between the intravenous and
      intrapulpal route and show the safety of pulpal transplantation of hDPSCs.

PMID- 29370944
TI  - Pigmentary keratopathy in a child: Histopathologic analysis.

PMID- 29370945
TI  - [Usefulness of thiopurine methyltransferase polymorphism study and metabolites
      measurement for patients treated by azathioprine].
AB  - Azathioprine is widely used in internal medicine and frequently implicated in
      occurrence of adverse events. Among these adverse events the bone marrow
      suppression, a dose-related one, is the most serious because of is potential
      morbidity and mortality. Severe myelosuppression, associated with abnormal AZA
      metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic
      polymorphism that results in a high variability of its activity with 89% of
      patients with a normal activity, 11% with an intermediate activity, and 0.3% with
      very low activity leading to a very high risk of bonne marrow suppression. TPMT
      status can be assessed prior to AZA treatment by measuring enzyme activity or
      genotyping techniques to identify patients for which the standard dose is not
      advisable. Furthermore, azathioprine metabolites monitoring is helpful for the
      follow up of patients, especially in therapeutic failure, to distinguish non
      compliant patients from under-dosed, "shunters" or resistant patients.

PMID- 29370946
TI  - Retrospective Chart Review of the Triage Algorithm for Psychiatric Screening
      (TAPS) for Patients Who Present to Emergency Departments With Psychiatric Chief
      Complaints.
AB  - INTRODUCTION: There is a growing number of mental health illnesses (MHIs) in the
      nation and no standardization of the medical screening examination (MSE) in the
      emergency department. Many health care organizations are at the tipping point of
      discarding a battery of laboratory workups. A triage tool-specific to psychiatric
      chief complaints and cost effective-is needed for the emergency department.
      METHODS: A nonexperimental, retrospective overlay of the Triage Algorithm for
      Psychiatric Screening (TAPS) onto previous psychiatric patients' records was
      performed to determine the sensitivity and specificity of the TAPS in ruling out
      acute medical illness. The laboratory test results, length of stay (LOS), and
      cost of treatment for all psychiatric patients were examined to determine if
      there was a correlation with their TAPS scores or if the use of the TAPS would
      have resulted in efficient care and cost savings. RESULTS: This study shows the
      TAPS tool can be used reliably to rule out acute medical illness in patients with
      psychiatric chief complaints in a community hospital setting with an on-site
      inpatient psychiatric unit. The TAPS tool appropriately identified low-acuity
      patients without significant medical illness (TAPS of 0). As such, the TAPS tool
      could be used in selected settings to expedite psychiatric care and reduce
      unnecessary laboratory testing. IMPLICATIONS FOR PRACTICE: The results of this
      project represent a valuable step forward in improving the triage of adult
      patients who present to the emergency department with psychiatric chief
      complaints. A reproducible study of the TAPS method was the next practice step in
      determining feasibility. Use of the TAPS tool can be a method to decease costs
      and ED crowding. For research and quality improvement projects in the future,
      addiction chief complaints should be treated as a separate category from
      psychiatric or medical complaints, as they meet the criteria of both.

PMID- 29370949
TI  - Heterogeneous structure and surface tension effects on mechanical response in
      pulmonary acinus: A finite element analysis.
AB  - BACKGROUND: The pulmonary acinus is a dead-end microstructure that consists of
      ducts and alveoli. High-resolution micro-CT imaging has recently provided
      detailed anatomical information of a complete in vivo acinus, but relating its
      mechanical response with its detailed acinar structure remains challenging. This
      study aimed to investigate the mechanical response of acinar tissue in a whole
      acinus for static inflation using computational approaches. METHODS: We performed
      finite element analysis of a whole acinus for static inflation. The acinar
      structure model was generated based on micro-CT images of an intact acinus. A
      continuum mechanics model of the lung parenchyma was used for acinar tissue
      material model, and surface tension effects were explicitly included. An
      anisotropic mechanical field analysis based on a stretch tensor was combined with
      a curvature-based local structure analysis. FINDINGS: The airspace of the acinus
      exhibited nonspherical deformation as a result of the anisotropic deformation of
      acinar tissue. A strain hotspot occurred at the ridge-shaped region caused by a
      rod-like deformation of acinar tissue on the ridge. The local structure becomes
      bowl-shaped for inflation and, without surface tension effects, the surface of
      the bowl-shaped region primarily experiences isotropic deformation. Surface
      tension effects suppressed the increase in airspace volume and inner surface
      area, while facilitating anisotropic deformation on the alveolar surface.
      INTERPRETATION: In the lungs, the heterogeneous acinar structure and surface
      tension induce anisotropic deformation at the acinar and alveolar scales. Further
      research is needed on structural variation of acini, inter-acini connectivity, or
      dynamic behavior to understand multiscale lung mechanics.

PMID- 29370948
TI  - Current opinion: What is a nanoplastic?
AB  - With the large amount of attention being given to microplastics in the
      environment, several researchers have begun to consider the fragmentation of
      plastics down to lower scales (i.e., the sub-micrometer scale). The term
      "nanoplastics" is still under debate, and different studies have set the upper
      size limit at either 1000 nm or 100 nm. The aim of the present work is to propose
      a definition of nanoplastics, based on our recently published and unpublished
      research definition of nanoplastics. We define nanoplastics as particles
      unintentionally produced (i.e. from the degradation and the manufacturing of the
      plastic objects) and presenting a colloidal behavior, within the size range from
      1 to 1000 nm.

PMID- 29370950
TI  - [Notions of epidemiology of value in dermatology].
AB  - Epidemiology, which was initially confined to the distribution of diseases in
      populations (descriptive epidemiology) and the factors responsible for such
      distribution (analytical epidemiology), also involves the evaluation of
      diagnostic and therapeutic strategies, as well as prognostic factors.
      Epidemiology provides elements that form the basis for medical and public health
      decisions. Information is collected from systematic records, which include large
      databases, or through specific surveys. Descriptive studies utilise mortality
      rates, as well as incidence and prevalence figures. The aim of aetiological
      epidemiology is to demonstrate a causal relationship between exposure and
      disease. It is necessary to check that studies do not present any major bias and
      to seek evidence in favour of causality. The strength of a causal relationship is
      calculated using relative risk or odds ratio. Other measurements of risk include
      attributable risk and aetiological fraction. Screening and diagnostic strategies
      are evaluated using the concepts of sensitivity, specificity, and above all,
      levels of likelihood that help determine the probability of a given patient
      becoming ill as a result of his or her personal characteristics and of test
      results. Evaluation of prognostic factors enables scores to be constructed
      allowing the probability of a given clinical outcome to be calculated as a
      function of patient characteristics.

PMID- 29370947
TI  - Caught with One's Zinc Fingers in the Genome Integrity Cookie Jar.
AB  - Zinc finger (ZnF) domains are present in at least 5% of human proteins. First
      characterized as binding to DNA, ZnFs display extraordinary binding plasticity
      and can bind to RNA, lipids, proteins, and protein post-translational
      modifications (PTMs). The diverse binding properties of ZnFs have made their
      functional characterization challenging. While once confined to large and poorly
      characterized protein families, proteomic, cellular, and molecular studies have
      begun to shed light on their involvement as protectors of the genome. We focus
      here on the emergent roles of ZnF domain-containing proteins in promoting genome
      integrity, including their involvement in telomere maintenance and DNA repair.
      These findings have highlighted the need for further characterization of ZnF
      proteins, which can reveal the functions of this large gene class in normal cell
      function and human diseases, including those involving genome instability such as
      aging and cancer.

PMID- 29370951
TI  - Reducing patient and provider knowledge gaps: An evaluation of a community
      informed hepatitis C online course.
AB  - OBJECTIVES: Hepatitis C (HCV) knowledge gaps are associated with lower levels of
      engagement in (HCV) care which contributes to HCV-related morbidity and
      mortality. Knowledge gaps may be exacerbated by rapid changes in HCV
      care/treatment. Cost-effective, timely and easy-to-implement education is needed
      to address knowledge gaps and foster HCV engagement. METHODS: We developed a
      free, one-hour, online course for patients and providers. Online and facilitated
      course events were evaluated. Outcome measures included: pre/post-scores,
      perceived knowledge gains and increased capacity to educate/encourage engagement
      in HCV care. RESULTS: Total pre-post-test gains were significant (p < .001)
      across groups. Over 50% of participants reported: perceived knowledge gains of "A
      lot" or higher; the course increased their capacity to educate and encourage
      client engagement in care by "A lot" or higher. CONCLUSIONS: The evaluation
      confirmed ongoing patient and provider HCV knowledge gaps, significantly reduced
      those gaps, and increased provider's capacity to educate and encourage client
      engagement in HCV care. PRACTICE IMPLICATIONS: The course is an effective tool to
      address knowledge gaps that might lower engagement in care. It is available to
      patients to use in the privacy of their own home or for providers for their
      personal use, to use with individuals or patient groups.

PMID- 29370952
TI  - A seminested PCR assay for detection and typing of human papillomavirus based on
      E1 gene sequences.
AB  - HPV infection is considered one of the leading causes of cervical cancer in the
      world. To date, more than 180 types of HPV have been described and viral typing
      is critical for defining the prognosis of cancer. In this work, a seminested PCR
      which allow fast and inexpensively detection and typing of HPV is presented. The
      system is based on the amplification of a variable length region within the viral
      gene E1, using three primers that potentially anneal in all HPV genomes. The
      amplicons produced in the first step can be identified by high resolution
      electrophoresis or direct sequencing. The seminested step includes nine specific
      primers which can be used in multiplex or individual reactions to discriminate
      the main types of HPV by amplicon size differentiation using agarose
      electrophoresis, reducing the time spent and cost per analysis.

PMID- 29370954
TI  - How to disentangle psychobiological stress reactivity and recovery: A comparison
      of model-based and non-compartmental analyses of cortisol concentrations.
AB  - This article seeks to address the prevailing issue of how to measure specific
      process components of psychobiological stress responses. Particularly the change
      of cortisol secretion due to stress exposure has been discussed as an
      endophenotype of many psychosomatic health outcomes. To assess its process
      components, a large variety of non-compartmental parameters (i.e., composite
      measures of substance concentrations at different points in time) like the area
      under the concentration-time curve (AUC) are commonly utilized. However, a
      systematic evaluation and validation of these parameters based on a
      physiologically plausible model of cortisol secretion has not been performed so
      far. Thus, a population pharmacokinetic (mixed-effects stochastic differential
      equation) model was developed and fitted to densely sampled salivary cortisol
      data of 10 males from Montreal, Canada, and sparsely sampled data of 200 mixed
      sex participants from Dresden, Germany, who completed the Trier Social Stress
      Test (TSST). Besides the two major process components representing (1) stress
      related cortisol secretion (reactivity) and (2) cortisol elimination (recovery),
      the model incorporates two additional, often disregarded components: (3) the
      secretory delay after stress onset, and (4) deviations from the projected steady
      state concentration due to stress-unrelated fluctuations of cortisol secretion.
      The fitted model (R2 = 99%) was thereafter used to investigate the correlation
      structure of the four individually varying, and readily interpretable model
      parameters and eleven popular non-compartmental parameters. Based on these
      analyses, we recommend to use the minimum-maximum cortisol difference and the
      minimum concentration as proxy measures of reactivity and recovery, respectively.
      Finally, statistical power analyses of the reactivity-related sex effect
      illustrate the consequences of using impure non-compartmental measures of the
      different process components that underlie the cortisol stress response.

PMID- 29370953
TI  - Spread of colistin resistance gene mcr-1 in Italy: characterization of the mcr
      1.2 allelic variant in a colistin-resistant blood isolate of Escherichia coli.
AB  - mcr-1.2, an allelic variant of the transferable colistin resistance gene mcr-1,
      was characterized in a colistin-resistant blood isolate of Escherichia coli. It
      was harbored by an IncX4-type plasmid (33,293 bp). Despite its low prevalence,
      the potentially worrying spread of the mcr-1 gene, particularly its mcr-1.2
      variant, in Italy requires increasing surveillance.

PMID- 29370955
TI  - A novel contour-based registration of lateral cephalogram and profile photograph.
AB  - A contour-based automatic registration method of lateral cephalograms and profile
      photographs is proposed to facilitate the accurate measurement of anteroposterior
      (AP) position of maxillary central incisors relative to the forehead. There are
      mainly three steps in the proposed method. First, a hierarchical contour
      detection algorithm is employed to obtain contours of forehead and nose in
      lateral cephalograms and profile photographs, respectively. Curve deviation
      around Nasion of Soft Tissue (Ns) is further corrected using an iterative
      polynomial curve fitting algorithm according to the characteristics of
      cephalograms. Second, the coarse registration is performed based on four landmark
      pairs using a routine least squares method for each image pair, and then the
      contours are roughly matched. Finally, the coarse registration is further refined
      by applying the coherent point drift (CPD) algorithm to all the contour points.
      Using image pairs of lateral cephalograms and profile photographs from 49 Chinese
      patients, we show that the proposed method achieves higher performance in terms
      of accuracy and robustness than the existing methods.

PMID- 29370956
TI  - Pediatric constrictive asphyxia a rare form of child abuse: A report of two
      cases.
AB  - We present two cases of infants who died under suspicious circumstances. After
      clinical and legal investigations, non-accidental constrictive asphyxia inflicted
      by one of the parents was established. The first case presents a to date not yet
      reported, unique mechanism of trauma. In order to stop his daughter from crying,
      the father admitted that he sometimes sat on his baby while she was lying on the
      bed. Occasionally increasing his force by pulling with his hands on the bottom of
      the bed. In the second case tight swaddling and encircling chest compression was
      the causative mechanism. In both cases the father was sentenced to imprisonment
      with mandate psychiatric care. Only two previous reports of this uncommon and
      relatively unknown cause of child abuse, called constrictive asphyxia, are known.
      In all reported cases static loading of the chest resulted in rib fractures and
      demise of the child. This rare abusive mechanism should be known to pediatric
      radiologists and pathologists.

PMID- 29370957
TI  - Effect of Bearing Type on Taper Material Loss in Hips From 1 Manufacturer.
AB  - BACKGROUND: Numerous studies have reported on clinical significant volumes of
      material loss and corrosion at the head-stem junction of metal-on-metal (MOM)
      hips; less is understood about metal-on-polyethylene (MOP) hips. We compared the
      effect of bearing type (MOM vs MOP) on taper material loss for a hip system of a
      single design. METHODS: In this cohort study, we recruited retrieved MOM (n = 30)
      and MOP (n = 22) bearing hips that were consecutively received at our center. We
      prospectively collected associated clinical and imaging data. We measured the
      severity of corrosion and volumes of material loss at each head taper surface and
      used multivariate statistical analysis to investigate differences between the 2
      bearing types. RESULTS: The median rate of material loss for the MOM and MOP
      groups was 0.81 mm3/y (0.01-3.45) and 0.03 mm3/y (0-1.07), respectively (P <
      .001). Twenty-nine of 30 MOM hips were revised for adverse metal reactions,
      compared with 1 of 22 MOP hips. CONCLUSION: MOP hips lost significantly less
      material from their taper junctions than MOM hips. Our results can reassure
      patients with MOP Pinnacle hips that they are unlikely to experience clinically
      significant problems related to material loss from the taper junction.

PMID- 29370958
TI  - Simultaneous homonuclear and heteronuclear spin decoupling in magic-angle
      spinning solid-state NMR.
AB  - We show here an effective way of implementing simultaneously homonuclear and
      heteronuclear dipolar decoupling in magic-angle spinning (MAS) solid-state NMR.
      Whilst the homonuclear spin decoupling is applied on the 1H channel,
      heteronuclear spin decoupling is applied on the 13C channel. The 1H spins are
      observed in a windowed fashion in this case. The resultant 1H spectrum has higher
      resolution due to the attenuation of broadening arising from both homonuclear 1H
      1H and heteronuclear 1H-13C interactions, with the latter normally leading to
      additional line broadening in 13C labelled samples. The experiments are performed
      at MAS frequencies of ca. 60 kHz.

PMID- 29370959
TI  - S.T.I.C.K.: A Quality Improvement Pediatric IV Infiltration Prevention Bundle.
AB  - Peripheral intravenous (PIV) catheters are commonly used in pediatric medical
      surgical orthopedic and neurology populations but are at risk of dislodgement
      with subsequent infiltration of fluids and/or medications. This quality
      improvement project sought to decrease the incidence of infiltration by creating
      an educational awareness program for both staff nurses and families using the
      S.T.I.C.K. mnemonic bundle. Rates of PIV catheter infiltration on a pediatric
      medical-surgical orthopedic and neurology unit were found to decrease when staff
      nurses utilized the S.T.I.C.K. mnemonic bundle while managing PIV catheter care
      for pediatric medical-surgical orthopedic and neurology patients.

PMID- 29370960
TI  - Video-based Education to Reduce Distress and Improve Understanding among
      Pediatric MRI Patients: A Randomized Controlled Study.
AB  - PURPOSE: Evaluate the effectiveness of an educational video vs. standard of care
      in improving relaxation and procedural understanding among pediatric patients
      undergoing a magnetic resonance imaging (MRI) procedure. DESIGN AND METHODS: This
      pilot randomized controlled trial was conducted in a large, urban academic
      children's hospital. Pediatric patients were randomized to receive either a 7
      minute educational video or standard of care. Standardized surveys, which
      consisted of a 1-10 visual analog scale and open-ended questions were
      administered to patients to measure their level of relaxation, understanding of
      the procedure, and perceptions of the MRI education received. Bivariate
      statistics were used to compare changes in relaxation score and baseline
      understanding scores between study groups. Open-ended questions were analyzed
      using content analysis. RESULTS: A total of 50 pediatric patients completed the
      study. Improvements in relaxation scores and baseline procedural understanding
      scores were significantly higher among children 13-17 years of age who received
      the intervention compared to those that did not (P < 0.05). No statistically
      significant differences were noted in relaxation scores and procedural
      understanding scores among children < 13 years of age between study groups. A
      total of 26 patients, half from the control group and half from the intervention
      group responded to open-ended survey questions. Content analysis revealed that
      nearly all respondents perceived the educational video to increase their
      understanding of the MRI procedure. CONCLUSIONS: Video-based education
      effectively improved the relaxation and procedural understanding of children 13
      17 years of age undergoing a MRI. PRACTICE IMPLICATIONS: Nurses may use video
      based education to supplement existing MRI education among older children.

PMID- 29370962
TI  - Evidence of noise-induced subclinical hearing loss using auditory brainstem
      responses and objective measures of noise exposure in humans.
AB  - Exposure to loud sound places the auditory system at considerable risk,
      especially when the exposure is routine. The current study examined the impact of
      routine auditory overexposure in young human adults with clinically-normal
      audiometric thresholds by measuring the auditory brainstem response (ABR), an
      electrophysiological measure of peripheral and central auditory processing. Sound
      exposure was measured objectively with body-worn noise dosimeters over a week.
      Participants were divided into low-exposure and high-exposure groups, with the
      low-exposure group having an average daily noise exposure dose of ~11% of the
      recommended exposure limit compared to the high-exposure group average of nearly
      500%. Compared to the low-exposure group, the high-exposure group had delayed
      ABRs to suprathreshold click stimuli and this prolongation was evident at ABR
      waves I and III but strongest for V. When peripheral differences were corrected
      using the I-V interpeak latency, the high-exposure group showed greater taxation
      at faster stimulus presentation rates than the low-exposure group, suggestive of
      neural conduction inefficiencies within central auditory structures. Our findings
      are consistent with the hypothesis that auditory overexposure affects peripheral
      and central auditory structures even before changes are evident on standard
      audiometry. We discuss our findings within the context of the larger debate on
      the mechanisms and manifestations of subclinical hearing loss.

PMID- 29370961
TI  - CXCR1 expression predicts benefit from tyrosine kinase inhibitors therapy in
      patients with metastatic renal cell carcinoma.
AB  - PURPOSE: CXCR1 signaling promotes tumor progression in various cancers, and
      clinical trial has proved efficacy of CXCR1 inhibitor in metastatic breast
      cancer. Therefore, we investigated the prognostic value of CXCR1 in patients with
      metastatic renal cell carcinoma (mRCC) receiving tyrosine kinase inhibitors
      (TKIs) therapy. MATERIALS AND METHODS: Patients treated with sunitinib or
      sorafenib were retrospectively enrolled (n = 111). CXCR1 expression was assessed
      by immunohistochemical staining of tissue microarrays of primary tumor, and its
      association with prognosis and therapeutic response were evaluated. To explore
      possible mechanism related to CXCR1 expression, gene set enrichment analysis was
      performed based on The Cancer Genome Atlas cohort. RESULTS: High CXCR1 expression
      was associated with poorer overall survival (P = 0.015) and was an independent
      prognostic factor for patients with mRCC treated by TKIs (Hazard Ratio = 1.683,
      95% Confidence Interval: 1.109-2.553, P = 0.014). CXCR1 expression was also
      associated with worse therapeutic response of TKIs (P = 0.017). Thirteen
      pathways, including hypoxia and angiogenesis, were identified to be enriched in
      CXCR1 positive patients. CONCLUSIONS: High CXCR1 expression indicates reduced
      benefit from TKIs therapy in patients with mRCC. The mechanism may be attributed
      to the enriched pathways of hypoxia and angiogenesis in CXCR1 positive patients.
      CXCR1 may be a potential therapeutic target for mRCC, but further studies are
      required.

PMID- 29370963
TI  - Comparisons of visual attention in school-age children with cochlear implants
      versus hearing peers and normative data.
AB  - OBJECTIVE: Previous research has found that preschoolers with hearing loss have
      worse visual attention and elevated rates of behavior problems when compared to
      typically hearing peers (Barker et al., 2009). However, little is known about
      these deficits in school-age children with cochlear implants (CIs). We evaluated
      visual selective attention in school-age children with CIs and hearing peers and
      examined the link between visual attention and behavior problems. METHOD: Data
      were drawn from the Childhood Development after Cochlear Implantation (CDaCI)
      study, the largest longitudinal, multi-site study of children with CIs. Visual
      attention was measured using d prime (d') on a continuous performance test (The
      Gordon CPT), which requires participants to watch a stream of digits and hit a
      button after seeing a certain target (a 9 following a 1). The CPT captures the
      probability of a hit (pressing button for a target) vs a false alarm (pressing
      the button for a non-target) while accounting for chance responding. In addition,
      predictors of visual attention, including IQ (using Processing Speed and
      Perceptional Reasoning on the WISC-IV), age at implantation, gender, and device
      management were examined. Externalizing problems were assessed using parent
      report on the BASC-2. Data were drawn from 60 months post-implantation. RESULTS:
      Children with CIs (n = 106) showed significantly worse visual selective attention
      than hearing peers. The difference in d' was driven by higher rates of false
      alarms. In the CI group, the Processing Speed Index on the WISC was correlated
      with total omissions, total commissions and d'. Within the CI group, d'
      significantly predicted parent-reported externalizing behavior problems. This
      finding was primarily driven by elevated Hyperactivity in the CI group.
      CONCLUSION: Children with CIs continue to display deficits in visual attention
      when compared to their hearing peers. Despite improvements in oral language,
      these problems have critical implications for academic performance and social
      competence. Currently, cochlear implant teams do not focus on these other
      dimensions of development and thus, may not be positioned to address them.
      Assessment of attention and behavior should be incorporated into routine, annual
      visits soon after implant surgery, and remediation of these deficits should be
      included in early intervention programs.

PMID- 29370966
TI  - Step by Step, One by One.

PMID- 29370964
TI  - The effect of community socioeconomic status on sepsis-attributable mortality.
AB  - PURPOSE: Community factors may play a role in determining individual risk for
      sepsis, as well as sepsis-related morbidity and mortality. We sought to define
      the relationship between community socioeconomic status and mortality due to
      sepsis in an urban locale. METHODS: Using community statistical areas of
      Baltimore City, we dichotomized neighborhoods at median household income, and
      compared distribution of outcomes of interest within the two income categories.
      We performed multivariable regression analyses to determine the relationship
      between socioeconomic variables and sepsis-attributable mortality. RESULTS: The
      collective median household income was $38,660 (IQR $32,530, 54,480), family
      poverty rate was 28.4% (IQR 13.5, 38.8%), and rate of death from sepsis was 3.1
      per 10,000 persons (IQR 2.60, 4.10). Lower household income communities
      demonstrated higher rates of death from sepsis (3.65 (IQR 2.78, 4.40)) than
      higher household income communities (2.80 (IQR 2.05, 3.55)) (p = .02). In
      regression models, household income (beta = -8.42, p = .006) and percentage of
      poverty in communities (beta = 2.71, p = .01) demonstrated associations with
      sepsis-attributable mortality. DISCUSSION: Our findings suggest that
      socioeconomic variables play significant role in sepsis-attributable mortality.
      Such confirmation of regional disparities in mortality due to sepsis warrants
      further consideration, as well as integration, for future national sepsis
      policies.

PMID- 29370965
TI  - Preventing brachial plexus injury during shoulder surgery: a real-time cadaveric
      study.
AB  - BACKGROUND: Brachial plexopathy is not uncommon after shoulder surgery. Although
      thought to be due to stretch neuropathy, its etiology is poorly understood. This
      study aimed to identify arm positions and maneuvers that may risk causing
      brachial plexopathy during shoulder arthroplasty. METHODS: Tensions in the cords
      of the brachial plexuses of 6 human cadaveric upper limbs were measured using
      load cells while each limb was placed in different arm positions and while they
      underwent shoulder hemiarthroplasty and revision reverse arthroplasty.
      Arthroplasty procedures in 4 specimens were performed with standard limb
      positioning (unsupported), and 2 specimens were supported from under the elbow
      (supported). Each cord then underwent biomechanical testing to identify tension
      corresponding to 10% strain (the stretch neuropathy threshold in animal models).
      RESULTS: Tensions exceeding 15 N, 11 N, and 9 N in the lateral, medial, and
      posterior cords, respectively, produced 10% strain. Shoulder abduction >70
      degrees  and combined external rotation >60 degrees  with extension >50 degrees 
      increased medial cord tension above the 10% strain threshold. Medial cord
      tensions (mean +/- standard error of the mean) in unsupported specimens increased
      over baseline during hemiarthroplasty (sounder insertion [4.7 +/- 0.6 N, P =
      .04], prosthesis impaction [6.1 +/- 0.8 N, P = .04], and arthroplasty reduction
      [5.0 +/- 0.7 N, P = .04]) and revision reverse arthroplasty (retractor
      positioning [7.2 +/- 0.8 N, P = .02]). Supported specimens experienced lower
      tensions than unsupported specimens. CONCLUSIONS: Shoulder abduction >70 degrees
      , combined external rotation >60 degrees  with extension >50 degrees , and
      downward forces on the humeral shaft may risk causing brachial plexopathy.
      Retractor placement, sounder insertion, humeral prosthesis impaction, and
      arthroplasty reduction increase medial cord tensions during shoulder
      arthroplasty. Supporting the arm from under the elbow protected the brachial
      plexus in this cadaveric model.

PMID- 29370967
TI  - [Reproducibility of bladder diary in patients with multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is a neurological condition characterized
      by variable levels of symptoms. This variability could also affect bladder
      dysfunction and impact on the reproducibility or stability of bladder diary (BD).
      The aim of the study is to investigate the reproducibility and reliability of BD
      in MS, and then determine its linked factors. METHODS: The MS patient provided a
      21 days BD and they documented the time of every void. The main criterion was
      assessed by voiding frequency, represented by the coefficient of variation
      (CV=average/standard deviation), expressed as a percentage. Two groups were
      described: stable BD group (CV<=15 %) and instable BD group (CV>15 %). Secondary
      criteria were completion of BD (complete or not) and the difference of voiding
      frequency variation between weekend and week. RESULTS: Thirty-one patients were
      included (mean age 51.06 years, SD 11.33) with 65 % of women. Mean CV is 23 % (SD
      0.11). The mean completion of BD was 19.35 days (SD 3.99). 8 patients had a
      CV<=15 %. Stable group was older than instable group (P=0.03). There was no other
      difference between the 2 groups. There is a strong correlation between mean
      voiding frequency weekend and week (rho=0.94, P<0.05). The longer duration of BD,
      the less reliability is notified. CONCLUSION: BD is not a stable reproducible in
      MS population. Both lack of compliance or variability of LUTS in MS may explain
      the unreliability of BD. However, BD utility should be discussed in this
      population. LEVEL OF EVIDENCE: 4.

PMID- 29370968
TI  - Floc behavior and removal mechanisms of cross-linked Durio zibethinus seed starch
      as a natural flocculant for landfill leachate coagulation-flocculation treatment.
AB  - This study investigated the behavior and mechanisms of cross-linked Durio
      zibethinus seed starch (CDSS) flocculants for landfill leachate treatment. A
      physical-chemical treatment method of coagulation-flocculation process and starch
      modification were implemented in treating stabilized leachate from Matang
      Landfill, Perak, Malaysia. In practical, the removal performance of color, COD,
      suspended solid and turbidity for CDSS flocculants were evaluated by combining
      with primary coagulant of polyaluminium chloride (PAC). In this study, the
      application of crosslinking modification for Durio zibethinus seed waste starch
      flocculants showed good improvement. The impurities removal for colour, COD,
      suspended solid and turbidity were increased by the addition of CDSS flocculants.
      Furthermore, the average size of the floc was also increased from 60.24 um to
      89.5 um. Despite, the addition of CDSS flocculants produced a reduction of PAC
      coagulant from 2700 mg/L to 2200 mg/L, with 500 mg/L reduction on the PAC dosage
      dependency. Therefore, these results affirmed the potentials of crosslinked
      modification for Durio zibethinus seed waste starch flocculants in landfill
      leachate treatment.

PMID- 29370969
TI  - Recycling of plastic wastes with poly (ethylene-co-methacrylic acid) copolymer as
      compatibilizer and their conversion into high-end product.
AB  - This paper deals with the utilization of plastic wastes to a useful product. The
      major plastic pollutants that are considered to be in maximum use i.e. PET bottle
      and PE bags have been taken for consideration for recycling. As these two plastic
      wastes are not compatible, poly (ethylene-co-methacrylic acid) copolymer has been
      used as compatibilizer to process these two plastic wastes. Effect of dose of
      poly (ethylene-co-methacrylic acid) copolymer as compatibilizer has been studied
      here. It has been shown that only 3 wt% of poly (ethylene-co-methacrylic acid)
      copolymer is sufficient to make 3:1 mass ratio of PET bottle and polyethylene
      bags compatible. Compatibility has been examined through mechanical testing,
      thermal and morphological analysis. After analysing the property of recyclates,
      better mechanical and thermal property has been observed. Almost 500% of tensile
      property has been improved by addition of 3 wt% of poly (ethylene-co-methacrylic
      acid) copolymer in 3:1 mass ratio blend of PET bottle and PE bags than that of
      pristine blend. Morphological analysis by FESEM and AFM has also confirmed the
      compatibility of the blend. Experimental data showed better performance than
      available recycling process.

PMID- 29370970
TI  - Association of long pentraxin-3 with pulmonary hypertension and primary graft
      dysfunction in lung transplant recipients.

PMID- 29370971
TI  - High-dose catecholamine donor support and outcomes after heart transplantation.
AB  - BACKGROUND: Higher dose norepinephrine donor support is a frequent reason for
      donor heart decline, but its associations with outcomes after heart
      transplantation are unclear. METHODS: We retrospectively analyzed 965 patients
      transplanted between 1992 and 2015 in the Heart Transplant Program Vienna.
      Stratification was performed according to donor norepinephrine dose administered
      before organ procurement (Group 0: 0 ug/kg/min; Group 1: 0.01 to 0.1 ug/kg/min;
      Group 2: >0.1 ug/kg/min). Sub-stratification of Group 2 was performed for
      comparison of high-dose subgroups (Group HD 1: 0.11 to 0.4 ug/kg/min; Group HD 2:
      >0.4 ug/kg/min). Associations between groups and outcome variables were
      investigated using a multivariable Cox proportional hazards model and logistic
      regression analyses. RESULTS: Donor norepinephrine dose groups were not
      associated with overall mortality (Group 1 vs 0: hazard ratio [HR] 1.12, 95%
      confidence interval [CI] 0.87 to 1.43; Group 2 vs 0: HR 1.07, 95% CI 0.82 to
      1.39; p = 0.669). No significant group differences were found for rates of 30-day
      mortality (p = 0.35), 1-year mortality (p = 0.897), primary graft dysfunction (p
      = 0.898), prolonged ventilation (p = 0.133) and renal replacement therapy (p =
      0.324). Groups 1 and 2 showed higher rates of prolonged intensive care unit stay
      (18.9% vs 28.5% vs 27.5%, p = 0.005). High-dose subgroups did not differ
      significantly in 1-year mortality (Group HD 1: 14.3%; Group HD 2: 17.8%; p =
      0.549). CONCLUSIONS: Acceptance of selected donor hearts supported by higher
      doses of norepinephrine may be a safe option to increase the donor organ pool.

PMID- 29370972
TI  - Optimal extent of surgical and pathologic lymph node evaluation for resected
      intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: Lymph node (LN) status is an important predictor of overall survival
      for resected IHCC, yet guidelines for the extent of LN dissection are not
      evidence-based. We evaluated whether the number of LNs resected at the time of
      surgery is associated with overall survival for IHCC. METHODS: Patients
      undergoing curative-intent (R0 or R1) resection for IHCC between 2004 and 2012
      were identified within the US National Cancer Database. LN thresholds were
      evaluated using maximal chi-square testing and five-year overall survival was
      modeled using Kaplan-Meier and Cox regressions. RESULTS: 57% (n = 1,132) of 2,000
      patients had one or more LNs resected and pathologically examined. In the 631
      patients undergoing R0 resection with pN0 disease, maximal chi-square testing
      identified >=3 LNs as the threshold most closely associated with overall
      survival. Only 39% of resections reached this threshold. On multivariable
      survival analysis, no threshold of LNs was associated with overall survival,
      including >=3 LNs (p = 0.186) and the current American Joint Committee on Cancer
      recommendation of >=6 LNs (p = 0.318). CONCLUSION: In determining the extent of
      lymphadenectomy at the time of curative-intent resection for IHCC, surgeons
      should carefully consider the prognostic yield in the absence of overall survival
      benefit.

PMID- 29370973
TI  - Induction of calcite precipitation through heightened production of extracellular
      carbonic anhydrase by CO2 sequestering bacteria.
AB  - The thermo-alkalotolerant bacterium exhibiting heightened extracellular carbonic
      anhydrase (CA) activity, survived at 100 mM sodium bicarbonateand 5% gaseous CO2
      was identified as Bacillus sp. by 16S rRNA sequencing. Extracellular carbonic
      anhydrase was purified by ammonium sulfate precipitation, gel filtration
      chromatography and affinity chromatography with a yield of 46.61% and specific
      activity of 481.66 U/mg. The size of purified carbonic anhydrase was
      approximately 28 kDa in SDS-PAGE gel filtration and further their role in calcium
      carbonate production was correlated. The purified enzyme was stable with half
      life of 25.36 min at 90  degrees C and pH 8. KM and Vmax values of the enzyme
      were 1.77 mg/mL and 385.69 U/mg respectively. The production of calcite was
      confirmed by Scanning Electron Microscopy (SEM) analysis, FTIR, and Energy
      Dispersive X-ray (EDX) analysis. Carbonic anhydrase and calcite deposition
      coupled with CO2 fixingbacteria is a significant approach for CO2 sequestration.

PMID- 29370974
TI  - Membrane concentrate treatment by photosynthetic bacteria: Feasibility and
      tolerance mechanism analysis.
AB  - Refractory membrane concentrate generated from the membrane bioreactor (MBR)
      process remains a big challenge. With high pollution loads, high salinity and low
      biodegradability, membrane concentrates are difficult to be treated by
      conventional biological treatments. In this work, photosynthetic bacteria (PSB)
      were employed to handle this problem. The results showed that PSB could
      simultaneously remove COD, NH3-N, NO3--N, salinity and chroma from the membrane
      concentrate. The removal efficiency of COD, NH3-N, NO3--N, salinity and chroma
      reached 24.0%, 78.0%, 81.6%, 57.0% and 60.0% respectively. Dark-aerobic condition
      was more beneficial for pollutants removal. The tolerance mechanism of PSB in
      treating membrane concentrate was then analyzed. The contents of protein and
      carotenoid in PSB increased by 38.7% and 20.7% due to the defense stress effects.
      The content of bacteriochlorin decreased by 42.9% while the content of coenzyme
      Q10 was stable at 8.4-8.8%.

PMID- 29370975
TI  - Design and synthesis of novel senkyunolide analogues as neuroprotective agents.
AB  - A class of senkyunolide analogues bearing benzofuranone fragment were designed,
      synthesized and evaluated for their neuroprotective effect in models of oxygen
      glucose deprivation (OGD) and oxidative stress. All tested compounds showed
      neuroprotection profile based on the cell viability assay. In particular,
      derivatives 1f-1i possessing furoxan-based nitric oxide releasing functionality
      exhibited significant biological activities in OGD models. More importantly,
      compound 1g containing short linker with furoxan displayed the most potent
      neuroprotection at the concentration of 100 MUM (cell survival up to 145.2%).
      Besides, 1g also showed the middle level neuroprotective effect in model of
      oxidative stress.

PMID- 29370976
TI  - Risk factors in childhood arterial ischaemic stroke: Findings from a population
      based study in Germany.
AB  - OBJECTIVE: Acute treatment of childhood arterial ischaemic stroke and prevention
      strategies for recurrent stroke episodes depend strongly on each child's
      individual risk profile. The aim of this study is to characterize risk factors
      for childhood stroke, their occurrence in isolation or combination, and to
      identify possible common risk factor patterns. METHODS: This population-based
      study was conducted via ESPED, a surveillance unit for rare paediatric diseases
      in Germany. Children aged >28days and <18 years with an acute arterial ischaemic
      stroke occurring between January 2015 and December 2016 were included. RESULTS:
      Among 99 reported children with arterial ischaemic stroke, 56 children were male.
      Male predominance was significant in adolescents from 12 years old onward.
      Arterial ischaemic stroke was more common in very young children <2 years of age
      and in adolescence. No risk factor was identified in 27 children. Hypercoagulable
      states (29%), cardiac disorders (24%), and arteriopathies (21%) were the most
      common risk factors. Some risk factor categories were more likely to be
      identified in isolation (i.e. cardiac disorders, prothrombotic abnormalities and
      chronic head and neck disorders) than others. The number of risk factors (n = 0
      4) per patient and risk factor categories did not differ by age. CONCLUSION:
      Although we could not identify common patterns of risk factor combinations,
      several risk factors occurred more likely in isolation than others. Further
      research should focus on the impact of isolated presumed childhood stroke risk
      factors like certain prothrombotic abnormalities, migraine or a patent foramen
      ovale. With regard to different age groups, stroke mechanisms in male adolescents
      require particular attention.

PMID- 29370977
TI  - Severe dysautonomia as a main feature of anti-GAD encephalitis: Report of a
      paediatric case and literature review.
AB  - INTRODUCTION: Anti-glutamic acid decarboxylase (anti-GAD65) antibodies are a rare
      cause of autoimmune encephalitis. This entity is mainly recognized in adults and
      very few cases were reported in children. We report on a paediatric case of anti
      GAD encephalitis with severe presentation and uncontrollable dysautonomia. CASE
      STUDY: A 9-year-old girl was referred to our department for refractory seizures
      and behavioral disturbances. Brain magnetic resonance imaging (MRI) was normal.
      Repeat screening for antineuronal antibodies showed negative results for anti
      NMDA receptor antibodies but positive results for anti-GAD65 with a low
      positivity of anti-Ma2 antibodies. Although a transient improvement was noticed
      after immunomodulatory treatment, the patient developed severe intractable
      autonomic imbalance including dysrythmia, alternating bradycardia/tachycardia,
      hypotension/hypertension, hypothermia/hyperthermia and hyperhidrosis. She
      deceased six months after onset. CONCLUSION: Our report intends to raise
      awareness of autoimmune encephalitis with anti-GAD65 antibodies which may involve
      extralimbic brain regions and manifest with fatal dysautonomia. We highlight the
      need for prompt diagnosis and aggressive management for this underdiagnosed
      entity in children.

PMID- 29370978
TI  - Comparing the Outcomes of Stereotactic Ablative Radiotherapy and Non-Stereotactic
      Ablative Radiotherapy Definitive Radiotherapy Approaches to Thoracic Malignancy:
      A Systematic Review and Meta-Analysis.
AB  - Stereotactic ablative body radiotherapy (SABR) is popular because of the high
      rates of local control with low toxicity seen in lung cancer patients. In this
      study we compared clinically significant toxicity and overall survival for SABR
      and non-SABR definitive radiotherapy (conformal radiotherapy) patients. A PUBMED
      search of all human, English language articles on SABR and non-SABR radically
      treated early stage lung cancer patients was performed until June 2016. Results
      of these searches were filtered in accordance with a set of eligibility criteria
      and analyzed in accordance with the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses guidelines. Eighty-seven SABR and 25 non-SABR articles
      were reviewed. There was no significant difference in pneumonitis rates between
      patients receiving SABR (11.4%; 95% confidence interval [CI], 9.7-13.3) and non
      SABR treatment (14.4%; 95% CI, 10.6-18.8; P = .20). Esophagitis was the most
      common mediastinal toxicity reported with 15% of all non-SABR patients versus 1%
      of all SABR patients reporting developing Grade >=2 toxicity. The proportion of
      patient surviving at 2 and 3 years was superior for SABR patients (P < .001).
      Treatment-related deaths were rare (approximately 1% for both treatments). Both
      radiotherapy approaches had low rates of pneumonitis, mediastinal toxicity, and
      treatment-related deaths. However, significant heterogeneity in the patient
      population and study regimens limit the power of direct comparison, showing that
      further high-quality studies are required to define the role of SABR in higher
      risk and operable patients.

PMID- 29370979
TI  - Bilateral Ischemic Stroke Due to Carotid Artery Compression by Abnormally
      Elongated Styloid Process at Both Sides: A Case Report.
AB  - Abnormal elongation of styloid process (Eagle syndrome) may cause compression of
      the adjacent structures in the neck, the most important of which is the carotid
      artery. This condition may cause damage to the wall of carotid artery and result
      in cerebrovascular ischemic event. Bilateral carotid artery damage and cerebral
      stroke because of overgrown styloid processes at both sides is a rare condition.
      In this article, we report a case of bilateral ischemic stroke because of carotid
      compression by elongated styloid process at both sides treated by surgical
      resection of both processes.

PMID- 29370980
TI  - Body balance at static posturography in vestibular migraine.
AB  - INTRODUCTION: Migraine is one of the most frequent and incapacitating headaches,
      with a high degree of impairment in quality of life. Its association with
      vestibular symptoms is common, including imbalance and postural instability.
      OBJECTIVE: To evaluate the body balance of patients with vestibular migraine
      through a static posturography test. METHODS: An experimental group of 31
      patients with a medical diagnosis of vestibular migraine in the intercritical
      period of the disease, and a control group of 31 healthy individuals, matched for
      age and gender, were submitted to the eight sensory conditions of the Tetrax
      Interactive Balance System. The parameters analyzed were: stability index, which
      measures the amount of sway, global stability and ability to compensate postural
      modifications; weight distribution index, which compares deviations in weight
      distribution; synchronization index, which measures the symmetry in the weight
      distribution; postural sway frequency, which indicates the frequency range with
      more sway; and fall risk index, which expresses the probability of falls.
      RESULTS: The stability index was higher in the experimental group in all eight
      sensory conditions, with a significant difference between the groups in six of
      them. The weight distribution index was higher in the experimental group in all
      conditions, with a significant difference in three of them. The number of cases
      with preferential sway in F2-F4 was significantly higher in the experimental
      group in three conditions, and in F5-F6 in two, while the fall risk was
      significantly higher in the experimental group than in the control group.
      CONCLUSION: Patients with vestibular migraine showed compromised body balance at
      the static posturography test.

PMID- 29370981
TI  - Enhanced production of extracellular inulinase by the yeast Kluyveromyces
      marxianus in xylose catabolic state.
AB  - The production of extracellular proteins by the thermotolerant yeast
      Kluyveromyces marxianus, which utilizes various sugars, was investigated using
      media containing sugars such as glucose, galactose, and xylose. SDS-PAGE analysis
      of culture supernatants revealed abundant production of an extracellular protein
      when cells were grown in xylose medium. The N-terminal sequence of the
      extracellular protein was identical to a part of the inulinase encoded by INU1 in
      the genome. Inulinase is an enzyme hydrolyzing beta-2,1-fructosyl bond in inulin
      and sucrose and is not required for xylose assimilation. Disruption of INU1 in
      the strain DMKU 3-1042 lost the production of the extracellular protein and
      resulted in growth defect in sucrose and inulin media, indicating that the
      extracellular protein was inulinase (sucrase). In addition, six K. marxianus
      strains among the 16 strains that were analyzed produced more inulinase in xylose
      medium than in glucose medium. However, expression analysis indicated that the
      INU1 promoter activity was lower in the xylose medium than in the glucose medium,
      suggesting that enhanced production of inulinase is controlled in a post
      transcriptional manner. The production of inulinase was also higher in cultures
      with more agitation, suggesting that oxygen supply affects the production of
      inulinase. Taken together, these results suggest that both xylose and oxygen
      supply shift cellular metabolism to enhance the production of extracellular
      inulinase.

PMID- 29370982
TI  - Production of lutein, and polyunsaturated fatty acids by the acidophilic
      eukaryotic microalga Coccomyxa onubensis under abiotic stress by salt or
      ultraviolet light.
AB  - In this study, the effect of abiotic stress on the acidophilic eukaryotic
      microalga, Coccomyxa onubensis, was analyzed for the production of lutein and
      PUFAs (polyunsaturated fatty acids). It grows autotrophically at a pH of 2.5. It
      showed a growth rate of 0.30 d-1, and produced approximately 122.50 mg.L-1.d-1
      biomass, containing lipids (300.39 mg g-1dw), lutein (5.30 mg g-1dw), and beta
      carotene (1.20 mg g-1dw). The fatty acid methyl ester (FAME) fraction was 89.70
      mg g-1dw with abundant palmitic acid (28.70%) and linoleic acid (37.80%). The
      addition of 100 mM NaCl improved the growth rate (0.54 d-1), biomass productivity
      (243.75 mg.L-1.d-1), and lipids accumulation (416.16 mg g-1dw). The microalga
      showed a lutein content of 6.70 mg g-1dw and FAME fraction of 118.90 mg g-1dw;
      68% of the FAMEs were PUFAs. However, when 200-500 mM salt was added, its growth
      was inhibited but there was a significant induction of lutein (up to 7.80 mg g
      1dw). Under continuous illumination with PAR (photosynthetically active
      radiations) +UVA (ultraviolet A, 8.7 W m-2), C. onubensis showed a growth rate of
      0.40 d-1, and produced 226.3 mg.L-1.d-1 biomass, containing lipids, (487.26 mg g
      1dw), lutein (7.07 mg g-1dw), and FAMEs (232.9 mg g-1dw); 48.4% of the FAME were
      PUFAs. The illumination with PAR + UVB (ultraviolet B, 0.16 W m-2) was toxic for
      cells. These results indicate that C. onubensis biomass is suitable as a
      supplement for functional foods and/or source of high added value products.

PMID- 29370983
TI  - Naturally Thin You: Weight Loss and Psychological Symptoms After a Six-Week
      Online Clinical EFT (Emotional Freedom Techniques) Course.
AB  - BACKGROUND/OBJECTIVE: Traditional methods of delivering therapeutic interventions
      have increasingly been supplemented by online courses. The current study
      investigated the effects of Clinical EFT (Emotional Freedom Techniques) in 76
      participants enrolled in a six-week online course called Naturally Thin You.
      Weight, restraint, the power of food in the external environment, happiness, and
      posttraumatic stress disorder (PTSD) symptoms were assessed before and after the
      course and at one-year follow-up. METHOD: Participants received six live group
      teleclasses, access to online course materials and a private social media group,
      and a year of monthly support teleclasses. No particular diet was recommended;
      the course focused instead on controlling emotional eating, and using EFT to
      treat the emotional triggers associated with food. Clinical EFTs Borrowing
      Benefits protocol, in which the group facilitator works with a single participant
      while others simultaneously self-apply EFT, was used during the teleclasses.
      RESULTS: Repeated measures ANOVA compared scores pre- to 12-month follow-up, and
      significant improvements were found for body weight (P < .001), depression
      symptoms (P = 0.010), restraint (P = 0.025), and the subjective power of food in
      the external environment (P = 0.018). Weight decreased an average of 1lb/week
      during the course, and 2lb/month between pretest and one-year follow-up. On
      follow-up, no change was observed in PTSD symptoms measured by a brief civilian
      trauma checklist, or anxiety, and increases in happiness were non-significant.
      The results indicate Clinical EFTs utility to address the influence of food in
      the external environment and assist weight loss, and to promote beneficial long
      term change when delivered in an online format.

PMID- 29370985
TI  - Skin CanceR Brachytherapy vs External beam radiation therapy (SCRiBE) meta
      analysis.
AB  - BACKGROUND AND PURPOSE: To compare cosmesis and local recurrence (LR) of
      definitive external beam radiation therapy (EBRT) vs brachytherapy (BT) for
      indolent basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the
      skin. MATERIALS AND METHODS: Studies including patients with T1-2 N0 SCCs/BCCs
      treated with definitive EBRT/BT and >=10 months follow-up were analyzed. The
      primary endpoint was post-treatment cosmesis, categorized as "good," "fair," or
      "poor." The secondary endpoint was LR. Mixed effects regression models were used
      to estimate weighted linear relationships between biologically equivalent doses
      with alpha/beta = 3 (BED3) and cosmetic outcomes. RESULTS: A total of 9965
      patients received EBRT and 553 received BT across 24 studies. Mean age was 73
      years, median follow-up was 36 months, and median dose was 45 Gy/10 fractions at
      4.4 Gy/fraction. At BED3 of 100 Gy, "good" cosmesis was more frequently observed
      in patients receiving BT, 95% (95% CI: 88-100%) vs 79% (95% CI: 60-82%), p <
      0.05. Similar results were found for "good" cosmesis at BED3 >100 Gy. No
      difference in "poor" cosmesis was noted at any BED3. LR was <7% for both at one
      year. CONCLUSION: BT has favorable cosmesis over EBRT for skin SCCs/BCCs at
      common fractionation regimens. Prospective studies comparing EBRT vs BT are
      warranted.

PMID- 29370984
TI  - Photon vs. proton radiochemotherapy: Effects on brain tissue volume and
      perfusion.
AB  - BACKGROUND AND PURPOSE: To compare the structural and hemodynamic changes of
      healthy brain tissue in the cerebral hemisphere contralateral to the tumor
      following photon and proton radiochemotherapy. MATERIALS AND METHODS: Sixty-seven
      patients (54.9 +/-14.0 years) diagnosed with glioblastoma undergoing adjuvant
      photon (n = 47) or proton (n = 19) radiochemotherapy with temozolomide after
      tumor resection underwent T1-weighted and arterial spin labeling MRI. Changes in
      volume and perfusion before and 3 to 6 months after were compared between
      therapies. RESULTS: A decrease in gray matter (GM) (-2.2%, P<0.001) and white
      matter (WM) (-1.2%, P<0.001) volume was observed in photon-therapy patients
      compared to the pre-radiotherapy baseline. In contrast, for the proton-therapy
      group, no significant differences in GM (0.3%, P = 0.64) or WM (-0.4%, P = 0.58)
      volume were observed. GM volume decreased with 0.9% per 10 Gy dose increase
      (P<0.001) and differed between the radiation modalities (P<0.001). Perfusion
      decreased in photon-therapy patients (-10.1%, P = 0.002), whereas the decrease in
      proton-therapy patients, while comparable in magnitude, did not reach statistical
      significance (-9.1%, P = 0.12). There was no correlation between perfusion
      decrease and either dose (P = 0.64) or radiation modality (P = 0.94).
      CONCLUSIONS: Our results show that the tissue volume decrease depends on
      radiation dose delivered to the healthy hemisphere and differs between treatment
      modalities. In contrast, the decrease in perfusion was comparable for both
      irradiation modalities. We conclude that proton therapy may reduce brain-volume
      loss when compared to photon therapy.

PMID- 29370986
TI  - Palliative radiotherapy for locally advanced non-metastatic head and neck cancer:
      A systematic review.
AB  - OBJECTIVES: The objective of this systematic review was to identify and appraise
      the existing evidence of role of palliative radiotherapy for locally advanced non
      metastatic head and neck cancer. METHODS: A systematic search of the literature
      was conducted using Medline, Embase and Cochrane databases and relevant
      references were included. RESULTS: Literature search revealed a wide variation in
      dose fractionation regimens. Reported outcomes showed high efficacy and low rate
      of significant side effects, except in studies utilising higher doses of
      radiotherapy where higher grade toxicities were seen. Reported median overall
      survival was in the range of 3.3-17 months, but most studies reported median
      survival of around 6 months. CONCLUSIONS: The choice of palliative radiotherapy
      varies significantly. This is in contrast to regimens of curative radiotherapy
      for locally advanced head and neck cancer, which are well standardised. Given the
      reported relatively short overall survival of this patient group, an ideal
      treatment should be of the shortest possible duration whilst ensuring effective
      palliation and minimal side effects. Future well designed trials are needed to
      evaluate quality of life and duration of side effects in addition to survival and
      severity of toxicities in this group of patients.

PMID- 29370987
TI  - Optimization of combined proton-photon treatments.
AB  - PURPOSE: Proton treatment slots are a limited resource. Therefore, we consider
      combined proton-photon treatments in which most fractions are delivered with
      photons and only a few with protons. We demonstrate how both modalities can be
      combined to optimally capitalize on the proton's ability to reduce normal tissue
      dose. METHODS: An optimal combined treatment must account for fractionation
      effects. We therefore perform simultaneous optimization of intensity-modulated
      proton (IMPT) and photon (IMRT) plans based on their cumulative biologically
      effective dose (BED). We demonstrate the method for a sacral chordoma patient, in
      whom the gross tumor volume (GTV) abuts bowel and rectum. RESULTS: In an optimal
      combination, proton and photon fractions deliver similar doses to bowel and
      rectum to protect these dose-limiting normal tissues through fractionation.
      However, proton fractions deliver, on average, higher doses to the GTV. Thereby,
      the photon dose bath is reduced. An optimized 30-fraction treatment with 10 IMPT
      fractions achieved more than 50% of the integral dose reduction in the
      gastrointestinal tract that is possible with 30 IMPT fractions (compared to 33%
      for a simple proton-photon combination in which both modalities deliver the same
      target dose). CONCLUSIONS: A limited number of proton fractions can best be used
      if protons hypofractionate parts of the GTV while maintaining near-uniform
      fractionation in dose-limiting normal tissues.

PMID- 29370988
TI  - Certolizumab pegol-induced palmoplantar pustulosis: A case report and review of
      the literature.

PMID- 29370989
TI  - Madelung's deformity.

PMID- 29370990
TI  - International access to major US cancer database halted.

PMID- 29370991
TI  - A start towards immunotherapy in sarcomas?

PMID- 29370993
TI  - Building capacity and wellbeing in vulnerable/marginalised mothers: A qualitative
      study.
AB  - PROBLEM: The persistence of health inequalities in pregnancy and infancy amongst
      vulnerable/marginalised groups in the UK. BACKGROUND: During pregnancy and early
      motherhood some women experience severe and multiple psychosocial and economic
      disadvantages that negatively affect their wellbeing and make them at increased
      risk of poor maternal and infant health outcomes. AIM: To explore
      vulnerable/marginalised women's views and experiences of receiving targeted
      support from a specialist midwifery service and/or a charity. METHODS: A mixed
      methods study was undertaken that involved analysis of routinely collected birth
      related/outcome data and interviews with a sample of vulnerable/marginalised
      women who had/had not received targeted support from a specialist midwifery
      service and/or a charity. In this paper we present in-depth insights from the 11
      women who had received targeted support. FINDINGS: Four key themes were
      identified; 'enabling needs-led care and support', 'empowering through knowledge,
      trust and acceptance', 'the value of a supportive presence' and 'developing
      capabilities, motivation and confidence'. DISCUSSION: Support provided by a
      specialist midwifery service and/or charity improved the maternity and parenting
      experiences of vulnerable/marginalised women. This was primarily achieved by
      developing a provider-woman relationship built on mutual trust and understanding
      and through which needs-led care and support was provided - leading to improved
      confidence, skills and capacities for positive parenting and health. CONCLUSION:
      The collaborative, multiagency, targeted intervention provides a useful model for
      further research and development. It offers a creative, salutogenic and health
      promoting approach to provide support for the most vulnerable/marginalised women
      as they make the journey into parenthood.

PMID- 29370992
TI  - Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance
      A091401): two open-label, non-comparative, randomised, phase 2 trials.
AB  - BACKGROUND: Patients with metastatic sarcoma have limited treatment options.
      Nivolumab and ipilimumab are monoclonal antibodies targeting PD-1 and CTLA-4,
      respectively. We investigated the activity and safety of nivolumab alone or in
      combination with ipilimumab in patients with locally advanced, unresectable, or
      metastatic sarcoma. METHODS: We did a multicentre, open-label, non-comparative,
      randomised, phase 2 study that enrolled patients aged 18 years or older and had
      central pathology confirmation of sarcoma with at least one measurable lesion by
      Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, evidence of
      metastatic, locally advanced or unresectable disease, an ECOG performance status
      of 0-1, and received at least one previous line of systemic therapy. Patients
      were assigned to treatment in an unblinded manner, as this trial was conducted as
      two independent, non-comparative phase 2 trials. Enrolled patients were assigned
      (1:1) via a dynamic allocation algorithm to intravenous nivolumab 3 mg/kg every 2
      weeks, or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses.
      Thereafter, all patients received nivolumab monotherapy (3 mg/kg) every 2 weeks
      for up to 2 years. The primary endpoint was the proportion of patients with
      locally advanced, unresectable or metastatic soft tissue sarcoma achieving a
      confirmed objective response. Analysis was per protocol. This study is ongoing
      although enrolment is closed. It is registered with ClinicalTrials.gov, number
      NCT02500797. FINDINGS: Between Aug 13, 2015, and March 17, 2016, 96 patients from
      15 sites in the USA underwent central pathology review for eligibility and 85
      eligible patients, including planned over-enrolment, were allocated to receive
      either nivolumab monotherapy (43 patients) or nivolumab plus ipilimumab (42
      patients). The primary endpoint analysis was done according to protocol
      specifications in the first 76 eligible patients (38 patients per group). The
      number of confirmed responses was two (5% [92% CI 1-16] of 38 patients) in the
      nivolumab group and six (16% [7-30] of 38 patients) in the nivolumab plus
      ipilimumab group. The most common grade 3 or worse adverse events were anaemia
      (four [10%] patients), decreased lymphocyte count (three [7%]), and dehydration,
      increased lipase, pain, pleural effusion, respiratory failure, secondary benign
      neoplasm, and urinary tract obstruction (two [5%] patients each) among the 42
      patients in the nivolumab group and anaemia (eight [19%] patients), hypotension
      (four [10%] patients), and pain and urinary tract infection (three [7%] patients
      each) among the 42 patients in the nivolumab plus ipilimumab group. Serious
      treatment-related adverse events occurred in eight (19%) of 42 patients receiving
      monotherapy and 11 (26%) of 42 patients receiving combination therapy, and
      included anaemia, anorexia, dehydration, decreased platelet count, diarrhoea,
      fatigue, fever, increased creatinine, increased alanine aminotransferase,
      increased aspartate aminotransferase, hyponatraemia, pain, pleural effusion, and
      pruritus. There were no treatment-related deaths. INTERPRETATION: Nivolumab alone
      does not warrant further study in an unselected sarcoma population given the
      limited efficacy. Nivolumab combined with ipilimumab demonstrated promising
      efficacy in certain sarcoma subtypes, with a manageable safety profile comparable
      to current available treatment options. The combination therapy met its
      predefined primary study endpoint; further evaluation of nivolumab plus
      ipilimumab in a randomised study is warranted. FUNDING: Alliance Clinical Trials
      in Oncology, National Cancer Institute Cancer Therapy Evaluation Program, Bristol
      Myers Squibb, Cycle for Survival.

PMID- 29370994
TI  - [Lower-extremity artery disease (LEAD)].
AB  - Women have a risk of LEAD (lower-extremity artery disease)similar to men's risk.
      Symptoms are often absent, atypical or underestimated, leading to diagnosis in
      the most severe stages. Medical care is often less well adapted. In cases of
      revascularization, women have a higher morbidity rate than men, regardless of the
      severity grade and procedure chosen.

PMID- 29370995
TI  - American Society for Metabolic and Bariatric Surgery estimation of metabolic and
      bariatric procedures performed in the United States in 2016.
AB  - BACKGROUND: Bariatric surgery, despite being the most successful long-lasting
      treatment for morbid obesity, remains underused as only approximately 1% of all
      patients who qualify for surgery actually undergo surgery. To determine if
      patients in need are receiving appropriate therapy, the American Society for
      Metabolic and Bariatric Surgery created a Numbers Taskforce to specify annual
      rate of use for obesity treatment interventions. OBJECTIVES: The objective of
      this study was to determine metabolic and bariatric procedure trends since 2011
      and to provide the best estimate of the number of procedures performed in the
      United States in 2016. SETTING: United States. METHODS: We reviewed data from the
      Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program,
      National Surgical Quality Improvement Program, Bariatric Outcomes Longitudinal
      Database, and Nationwide Inpatient Sample. In addition, data from industry and
      outpatient centers were used to estimate outpatient center activity. Data from
      2016 were compared with the previous 5 years of data. RESULTS: Compared with
      2015, the total number of metabolic and bariatric procedures performed in 2016
      increased from approximately 196,000 to 216,000. The sleeve gastrectomy trend is
      increasing, and it continues to be the most common procedure. The gastric bypass
      and gastric band trends continued to decrease as seen in previous years. The
      percentage of revision procedures and biliopancreatic diversion with duodenal
      switch procedures increased slightly. Finally, intragastric balloons placement
      emerged as a significant contributor to the cumulative total number of procedures
      performed. CONCLUSIONS: There is increasing use of metabolic and bariatric
      procedures performed in the United States from 2011 to 2016, with a nearly 10%
      increase noted from 2015 to 2016.

PMID- 29370997
TI  - Department of Error.

PMID- 29370996
TI  - Endoscopic stent placement for treatment of sleeve gastrectomy leak: a single
      institution experience with fully covered stents.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (SG) has risen in prevalence as a
      standalone surgical option for treating obesity over the last 15 years. One of
      the most worrisome complications is development of a leak at the gastrectomy
      staple line. OBJECTIVE: The objective of this report is to describe our single
      institution experience in managing SG staple-line leaks with fully covered
      endoscopic stents. SETTING: Academic medical center, United States. METHODS: Data
      for all patients who underwent endoscopic stent placement for an SG leak between
      2010 and 2016 at a single academic institution were retrospectively reviewed.
      Patient medical history, perioperative information, stent placement details,
      outcomes, and subsequent interventions were recorded. RESULTS: Twenty-four
      patients with SG staple-line leaks treated with fully covered endoscopic stents
      were identified. Leaks were identified at a median of 31.5 days postoperatively
      (range, 1-1615 d). The majority of patients underwent other treatment(s) for
      their leak before stent placement at our institution. Stents remained in place
      for an average of 28.8 +/- 16.8 days. Migration occurred in 22% of all stent
      placements. Three patients were lost to follow-up, and 14 of the remaining 21
      patients (66.7%) healed after stent placement. Five patients (23.8%) ultimately
      required operative revision with partial gastrectomy and Roux-en-Y
      esophagojejunostomy for management of persistent leaks. CONCLUSION: Endoscopic
      management using fully covered stents for staple-line leaks after SG is effective
      in the majority of patients. However, algorithms are needed for the management of
      chronic staple-line leaks, which are less likely to heal with stent placement.

PMID- 29370998
TI  - Optimal hemoglobin A1C cutoff value for diabetes mellitus and pre-diabetes in
      Pudong New Area, Shanghai, China.
AB  - AIMS: Due to the diversity of the Chinese population, it requires considerable
      research to evaluate HbA1c diagnostic threshold for diagnosis of hyperglycemia.
      METHODS: We included 7909 subjects aged >=15 without known diabetes from the
      baseline of Pudong community cohort in 2013. Participants took oral glucose
      tolerance test (OGTT) and HbA1c assay. Receiver operating characteristic curve
      determined the HbA1c threshold in the diagnosis of hyperglycemia. RESULTS: The
      optimal HbA1C threshold for diagnosing newly diagnosed diabetes (NDD) and pre
      diabetes in this population was 6.0% (AUC=0.798, 95%CI: 0.779-0.818) and 5.6%
      (AUC=0.655, 95%CI: 0.638-0.671). When compared with elderly age group (>=70
      years), HbA1c for detecting NDD performed better in youth (15-39 years: P=0.003,
      40-49 years: P<0.001). There were 13.81% and 13.34% of participants would be
      newly detected as NDD and pre-diabetes via HbA1c criteria; meanwhile 3.20% and
      15.52% diagnosed as NDD and pre-diabetes by OGTT criteria would be missed
      diagnosis. CONCLUSIONS: The optimal HbA1c thresholds for NDD and pre-diabetes
      were lower than ADA criteria. It is necessary to carefully consider whether
      choose HbA1c as a diagnostic criterion or combine two diagnostic standards. Age
      specific diagnostic thresholds should be considered when HbA1c was recommended as
      diagnostic standard.

PMID- 29370999
TI  - A comparison of three apolipoprotein B methods and their associations with
      incident coronary heart disease risk over a 12-year follow-up period: The Multi
      Ethnic Study of Atherosclerosis.
AB  - BACKGROUND: Apolipoprotein B-100 (ApoB) is a well-researched lipoprotein marker
      used in assessing the risk of coronary heart disease (CHD) development. Despite
      its continued use at the bedside, ApoB methodologies have not been thoroughly
      compared and may differentially discriminate CHD risk, resulting in patient
      misclassification. OBJECTIVE: This study compared 3 ApoB immunoassays and their
      associations with incident CHD risk over a 12-year follow-up period in the Multi
      Ethnic Study of Atherosclerosis. METHODS: Plasma ApoB concentrations were
      measured in 4679 participants of Multi-Ethnic Study of Atherosclerosis at
      baseline, using 3 immunoturbidimetric methods. Roche and Kamiya reagent-based
      methods were analyzed on a Roche modular P analyzer, and the Diazyme reagent
      based method was analyzed on a Siemens Dimension analyzer. Cox proportional
      analysis estimated ApoB-related risk of incident CHD over a median follow-up
      period of 12.5 years with adjustments for nonlipid CHD risk factors. ApoB
      concentrations were examined as continuous variables but were also dichotomized
      based on clinical designations of borderline (100 mg/dL), high (120 mg/dL), and
      very high ApoB levels (140 mg/dL). RESULTS: Moderate to strong correlations among
      ApoB methods were observed (r = 0.79-0.98). ApoB concentrations (per standard
      deviation) were similarly associated with CHD risk and hazard ratio (95%
      confidence interval): Roche: 1.16 (1.03-1.30); Kamiya: 1.14 (1.02-1.28); and
      Diazyme: 1.14 (1.02-1.28). CONCLUSION: Although all 3 ApoB were similarly
      associated with risk of incident CHD over the study period regardless of the
      reagent type, the bias between methods suggests that these reagents are not
      fungible, and assay harmonization may be warranted.

PMID- 29371000
TI  - Pasireotide in acromegaly by aggressive tumors, description of four clinical
      cases. Towards a personalized medicine.

PMID- 29371001
TI  - Change over time in the incidence of type 1 diabetes mellitus in Spanish
      children.

PMID- 29371002
TI  - The predictive value of NT-proBNP and hs-TnT for risk of death in cardiac
      surgical patients.
AB  - BACKGROUND: European System for Cardiac Operative Risk Evaluation II (EuroSCORE
      II) is used for risk stratification before cardiac surgery, but whether N
      terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin
      T (hs-TnT) may add prognostic information to EuroSCORE II is not known. METHODS:
      Preoperative (n=640) and postoperative (n=629) blood samples were available from
      cardiac surgical patients with 961-day follow-up (FINNAKI Heart study; cohort
      #1). The accuracy of a parsimonious risk model with NT-proBNP measurements was
      also tested in 90 patients with respiratory failure after cardiac surgery
      (FINNALI study; cohort #2). RESULTS: Sixty-one patients (9.5%) died during follow
      up in cohort #1. Preoperative NT-proBNP and hs-TnT concentrations correlated
      (rho=0.58; p<0.001) and were higher in non-survivors compared to survivors:
      median 2027 (Q1-3 478-5387) vs. 373 (134-1354) ng/L [NT-proBNP] and 39 (16-191)
      vs. 13 (8-32) ng/L [hs-TnT]; p<0.001 for both. Preoperative NT-proBNP
      concentrations were associated with time to death after adjustment for EuroSCORE
      II (HR [lnNT-proBNP] 1.33 [95% CI 1.08-1.64]), p=0.008 and reclassified patients
      on top of EuroSCORE II (net reclassification index 0.39 [95% CI 0.14-0.64],
      p=0.003). Pre- and postoperative NT-proBNP concentrations were closely correlated
      (rho=0.80, p<0.001) and postoperative NT-proBNP concentrations were also
      associated with long-term mortality after adjustment for EuroSCORE II. A
      parsimonious risk model that included age, creatinine clearance, chronic
      pulmonary disease, and NT-proBNP measurements provided comparable prognostic
      accuracy as EuroSCORE II in cohort #1 and #2 for risk of long-term mortality. hs
      TnT measurements did not add to NT-proBNP measurements CONCLUSION: NT-proBNP
      measurements could improve and simplify risk prediction in cardiac surgical
      patients.

PMID- 29371003
TI  - How Sensors, Devices, and Biomarkers Can Transform Precision Medicine:
      Perspectives From a Clinical and Translational Science Institute.
AB  - PURPOSE: The ability of sophisticated sensors and medical devices to monitor
      critical biomarkers has the potential to greatly advance precision medicine
      initiatives. A stakeholder event was organized to develop working models for the
      evolution of the field. METHODS: A workshop devoted to the subject matter was
      held at the Tufts Clinical and Translational Science Institute involving
      clinicians, device developers, regulators, engineers, and scientists. FINDINGS:
      Several areas for collaborative development were identified and interested teams
      offered resources for development of research programs. IMPLICATIONS: The
      diversity of relevant stakeholders presents a major opportunity and challenge in
      translational research. It is evident that the CTSI national network can take a
      leadership role in the rapidly advancing and potentially transformative field of
      digital biomarkers.

PMID- 29371005
TI  - Perception and Practice Among Emergency Medicine Health Care Providers Regarding
      Discharging Patients After Opioid Administration.
AB  - PURPOSE: This study aimed to determine the current attitudes, perceptions, and
      practices of emergency medicine providers and nurses (RNs) regarding the
      discharge of adult patients from the emergency department (ED) after
      administration of opioid analgesics. METHODS: A cross-sectional survey was
      administered at 3 hospital sites with a combined annual ED census of >180,000
      visits per year. All 59 attending emergency physicians (EPs), 233 RNs, and 23
      advanced practice clinicians (APCs) who worked at these sites were eligible to
      participate. FINDINGS: Thirty-five EPs (59.3%), 88 RNs (37.8%), and 14 APCs
      (60.9%) completed the survey for an overall response rate of 51.75%. Most
      respondents were female (95 [69.9%]). The factor ranked most important to
      consider when discharging a patient from the ED after administration of opioids
      was the patient's functional status and vital signs (median, 2.00; interquartile
      range, 2.00-3.50). More RNs (84 [96.6%]) than EPs (29 [82.9%]) reported that
      developing an ED policy or guideline for safe discharge after administration of
      opioids is important to clinical practice (P = 0.02). Only 8 physicians (23.5%)
      reported that they did not prescribe intramuscular morphine, and 15 (42.9%)
      reported that they did not prescribe intramuscular hydromorphone. EPs (7 [20.0%])
      and RNs (3 [3.4%]) differed in regard to whether they were aware if any patients
      to whom they administered an opioid had experienced an adverse drug-related event
      (P = 0.01). Most EPs (24 [68.6%]) and RNs (54 [61.4%]) believed that the decision
      for patient discharge should be left to both the emergency medicine provider and
      the RN. IMPLICATIONS: Most study participants believed that developing a policy
      or guideline for safe discharge after administration opioids in the ED is
      important to clinical practice. Only a few physicians reported that they did not
      prescribe intramuscular hydromorphone or morphine. Most participants believed the
      discharge decision after administration of opioids in the ED should be primarily
      determined by both the emergency medicine provider and the RN.

PMID- 29371004
TI  - Gender Differences in Pain Experience and Treatment after Motor Vehicle
      Collisions: A Secondary Analysis of the CRASH Injury Study.
AB  - PURPOSE: Little is known about gender differences in the treatment of pain after
      motor vehicle collisions (MVCs) in an emergency department (ED). We aimed to
      describe gender differences in pain experiences and treatment, specifically the
      use of opioids and benzodiazepines after ED discharge, for MVC-related pain.
      METHODS: This was a secondary analysis of previously collected data from the
      CRASH Injury studies. We included patients who were seen and discharged from an
      ED after an MVC and who were enrolled in 1 of 2 multicenter longitudinal
      prospective cohort studies (1 black/non-Hispanic and 1 white/non-Hispanic).
      First, we compared the experience of pain as defined by self-reported moderate-to
      severe axial pain, widespread pain, number of somatic symptoms, pain
      catastrophizing, and peritraumatic distress between women and men using bivariate
      analyses. We then determined whether there were gender differences in the receipt
      of prescription medications for post-MVC pain symptoms (opioids and
      benzodiazepines) using multivariate logistic regression adjusting for demographic
      characteristics, pain, and collision characteristics. FINDINGS: In total, 1878
      patients were included: 61.4% were women. More women reported severe symptoms on
      the pain catastrophizing scale (36.8% vs 31.0%; P = 0.032) and peritraumatic
      distress following the MVC (59.7% vs 42.5%; P < 0.001), and women reported more
      somatic symptoms than men (median, 3.9; interquartile range, 3.7-4.0 vs median,
      3.3; interquartile range, 3.1-3.5; P < 0.001). Unadjusted, similar proportions of
      women and men were given opioids (29.2% vs 29.7%; P = 0.84). After adjusting for
      covariates, women and men remained equally likely to receive a prescription for
      opioids (relative risk = 0.83; 95% confidence interval, 0.58-1.19). Women were
      less likely than men to receive a benzodiazepine at discharge from an ED
      (relative risk = 0.53; 95% confidence interval, 0.32-0.88). IMPLICATIONS: In a
      large, multicenter study of ED patients treated for MVC, there were gender
      differences in the acute psychological response to MVC with women reporting more
      psychological and somatic symptoms. Women and men were equally likely to receive
      opioid prescriptions at discharge. Future research should investigate potential
      gender-specific interventions to reduce both posttraumatic distress and the risk
      of developing negative long-term outcomes like chronic pain.

PMID- 29371006
TI  - [Circumflex arising from the right coronary sinus: echocardiographic image].

PMID- 29371007
TI  - Efficacy and Safety of Ranibizumab 0.5 mg for the Treatment of Macular Edema
      Resulting from Uncommon Causes: Twelve-Month Findings from PROMETHEUS.
AB  - PURPOSE: To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult
      patients with macular edema (ME) resulting from any cause other than diabetes,
      retinal vein occlusion, or neovascular age-related macular degeneration. DESIGN:
      A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter
      study. PARTICIPANTS: One hundred seventy-eight eligible patients aged >=18 years.
      METHODS: Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n =
      118) or sham (n = 60) at baseline and month 1. From month 2, patients in both
      arms received open-label individualized ranibizumab treatment based on disease
      activity. A preplanned subgroup analysis was conducted on the primary end point
      on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic
      or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous).
      MAIN OUTCOME MEASURES: Changes in best-corrected visual acuity (BCVA; Early
      Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary
      end point) and month 12 and safety over 12 months. RESULTS: Overall, 156 patients
      (87.6%) completed the study. The baseline characteristics were well balanced
      between the treatment arms. Overall, ranibizumab showed superior efficacy versus
      sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9
      letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters.
      The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab.
      The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging
      from >5-letter gain to 0.5-letter loss. The safety findings were consistent with
      the well-established safety profile of ranibizumab. CONCLUSIONS: The primary end
      point was met and ranibizumab showed superiority in BCVA gain over sham in
      treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at
      month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the
      ranibizumab arm; however, the TE was observed to be variable across the different
      etiology subgroups, reaching a >1-line TE in BCVA in patients with ME resulting
      from inflammatory conditions/post-uveitis or after cataract surgery. Overall,
      ranibizumab was well tolerated with no new safety findings up to month 12.

PMID- 29371008
TI  - Myopia Prevention and Outdoor Light Intensity in a School-Based Cluster
      Randomized Trial.
AB  - PURPOSE: To investigate the effectiveness of a school-based program promoting
      outdoor activities in Taiwan for myopia prevention and to identify protective
      light intensities. DESIGN: Multi-area, cluster-randomized intervention controlled
      trial. PARTICIPANTS: A total 693 grade 1 schoolchildren in 16 schools
      participated. Two hundred sixty-seven schoolchildren were in the intervention
      group and 426 were in the control group. METHODS: Initially, 24 schools were
      randomized into the intervention and control groups, but 5 and 3 schools in the
      intervention and control groups, respectively, withdrew before enrollment. A
      school-based Recess Outside Classroom Trial was implemented in the intervention
      group, in which schoolchildren were encouraged to go outdoors for up to 11 hours
      weekly. Data collection included eye examinations, cycloplegic refraction,
      noncontact axial length measurements, light meter recorders, diary logs, and
      questionnaires. MAIN OUTCOME MEASURES: Change in spherical equivalent and axial
      length after 1 year and the intensity and duration of outdoor light exposures.
      RESULTS: The intervention group showed significantly less myopic shift and axial
      elongation compared with the control group (0.35 diopter [D] vs. 0.47 D; 0.28 vs.
      0.33 mm; P = 0.002 and P = 0.003) and a 54% lower risk of rapid myopia
      progression (odds ratio, 0.46; 95% confidence interval [CI], 0.28-0.77; P =
      0.003). The myopic protective effects were significant in both nonmyopic and
      myopic children compared with controls. Regarding spending outdoor time of at
      least 11 hours weekly with exposure to 1000 lux or more of light, the
      intervention group had significantly more participants compared with the control
      group (49.79% vs. 22.73%; P < 0.001). Schoolchildren with longer outdoor time in
      school (>=200 minutes) showed significantly less myopic shift (measured by light
      meters; >=1000 lux: 0.14 D; 95% CI, 0.02-0.27; P = 0.02; >=3000 lux: 0.16 D; 95%
      CI, 0.002-0.32; P = 0.048). CONCLUSIONS: The school-based outdoor promotion
      program effectively reduced the myopia change in both nonmyopic and myopic
      children. Outdoor activities with strong sunlight exposure may not be necessary
      for myopia prevention. Relatively lower outdoor light intensity activity with
      longer time outdoors, such as in hallways or under trees, also can be considered.

PMID- 29371009
TI  - Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain
      Malignant Potential.
AB  - PURPOSE: Uveal melanoma (UM) is the most common primary intraocular malignancy in
      adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality
      rate. The genetic changes in iris melanoma are not as well characterized as
      ciliary body or choroidal melanoma. The aim of this study was to gain more
      insight into the genetic background of iris melanoma and iris nevi. DESIGN:
      Multicenter, retrospective case series. PARTICIPANTS: Patients diagnosed with
      iris melanoma or iris nevi who underwent surgical intervention as primary or
      secondary treatment. METHODS: Next-generation sequencing of GNAQ, GNA11, EIF1AX,
      SF3B1, BAP1, NRAS, BRAF, PTEN, c-Kit, TP53, and TERT was performed on 30 iris
      melanomas and 7 iris nevi. Copy number status was detected using single
      nucleotide polymorphisms (SNPs) included in the next-generation sequencing (NGS)
      panel, SNP array, or fluorescent in situ hybridization. BAP1 immunohistochemistry
      was performed on all samples. MAIN OUTCOME MEASURES: Mutation and copy number
      status were analyzed. Results of BAP1 immunohistochemistry were used for survival
      analysis. RESULTS: In 26 of the 30 iris melanoma and all iris nevi, at least 1
      mutation was identified. Multiple mutations were detected in 23 iris melanoma and
      5 nevi, as well as mutations in GNAQ and GNA11. Furthermore, 13 of 30 BAP1, 5 of
      30 EIF1AX, and 2 of 30 SF3B1 mutations were identified in iris melanoma. No
      correlation between BAP1 status and disease-free survival was found. The iris
      nevi showed 1 EIF1AX and 3 BAP1 mutations. Two of the nevi, with a BAP1 mutation,
      were histologically borderline malignant. Mutations in NRAS, BRAF, PTEN, c-KIT,
      and TP53 were detected in 6 iris melanomas and 4 iris nevi. CONCLUSIONS:
      Mutations that are often found in uveal and cutaneous melanoma were identified in
      this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a
      molecular profile comparable to both choroidal melanoma and cutaneous melanoma.
      These findings may offer adjuvant targeted therapies for iris melanoma. There was
      no prognostic significance of BAP1 expression as seen in choroidal melanoma.
      Consequently, iris melanoma is a distinct molecular subgroup of UM. Histologic
      borderline malignant iris nevi can harbor BAP1 mutations and may be designated
      iris melanocytic tumors of uncertain malignant potential.

PMID- 29371010
TI  - The Discrepancy between Subjective and Objective Measures of Convergence
      Insufficiency in Whiplash-Associated Disorder versus Control Participants.
AB  - PURPOSE: Motor vehicle accidents (MVAs) are a pandemic associated with human
      suffering and a burden to national economies. Whiplash-associated disorders
      (WADs) after MVAs are associated commonly with disability claims, many of which
      are related to vision. Convergence insufficiency (CI) leads to visual disability
      associated with symptoms of ocular discomfort. We examined the incidence of
      symptoms and findings consistent with CI in a cohort of patients after MVA
      related WAD compared with age-matched control participants. DESIGN: Prospective
      cohort study. PARTICIPANTS: Patients with WAD after MVA were recruited from the
      Orthopedic Emergency Department between July 2014 and March 2017. Control
      participants were recruited among hospital personnel and relatives of WAD
      patients. METHODS: The Convergence Insufficiency Symptom Survey (CISS)
      questionnaire was completed by each participant, followed by a detailed visual
      examination including measurements of distance and near best-corrected Snellen
      visual acuity, distance and near cover test, Randot stereopsis, Maddox distance
      and Maddox-Thorington near heterophoria, near point of convergence, base-out step
      fusional reserves, and amplitude of accommodation using the push-away method.
      MAIN OUTCOME MEASURES: The CISS score and binocular measure findings of CI were
      recorded and analyzed using Student's t test, the chi-square test, and multiple
      logistic regression adjusted for age and gender. RESULTS: A pathologic CISS score
      of 16 or more occurred in 26 of 57 WAD patients (45.6%) compared with 6 of 39
      control participants (15.4%; P = 0.002). Absolute CISS score was higher in the
      WAD group compared with the control group (15.3+/-10.0 vs. 7.7+/-7.7; P < 0.001).
      Findings consistent with CI occurred in 7.0% of WAD patients and 7.7% of control
      participants (P = 0.90). CONCLUSIONS: Visual symptoms suggestive of CI were
      reported more frequently among WAD patients compared with control participants,
      yet the incidence of examination findings indicating weakness of convergence was
      not increased. The discrepancy between subjective and objective measures of CI in
      WAD patients versus control participants stresses the importance of training
      healthcare personnel to assess disability using objective, validated standards of
      examination.

PMID- 29371011
TI  - Progression of Myopic Maculopathy during 18-Year Follow-up.
AB  - PURPOSE: To examine the progression pattern of myopic maculopathy. DESIGN:
      Retrospective, observational case series. PARTICIPANTS: Highly myopic patients
      who had been followed up for 10 years or more. METHODS: Using fundus photographs,
      myopic features were differentiated according to Meta-analysis of Pathologic
      Myopia (META-PM) Study Group recommendations. MAIN OUTCOME MEASURES: Progression
      pattern of maculopathy. RESULTS: The study included 810 eyes of 432 patients
      (mean age, 42.3+/-16.8 years; mean axial length, 28.8+/-1.9 mm; mean follow-up,
      18.7+/-7.1 years). The progression rate of myopic maculopathy was 47.0 per 1000
      eye-years. Within the pathologic myopia (PM) group (n = 521 eyes), progression of
      myopic maculopathy was associated with female gender (odds ratio [OR], 2.21; P =
      0.001), older age (OR, 1.03; P = 0.002), longer axial length (OR, 1.20; P =
      0.007), greater axial elongation (OR, 1.45; P = 0.005), and development of
      parapapillary atrophy (PPA; OR, 3.14; P < 0.001). Diffuse atrophy, found in 217
      eyes without choroidal neovascularization (CNV) or lacquer cracks (LCs) at
      baseline, progressed in 111 (51%) eyes, leading to macular diffuse atrophy (n =
      64; 64/111 or 58%), patchy atrophy (n = 59; 53%), myopic CNV (n = 18; 16%), LCs
      (n = 9; 5%), and patchy-related macular atrophy (n = 3; 3%). Patchy atrophy,
      detected in 63 eyes without CNV or LCs at baseline, showed progression in 60 eyes
      (95%), leading to enlargement of original patchy atrophy (n = 59; 59/60 or 98%),
      new patchy atrophy (n = 29; 48%), CNV-related macular atrophy (n = 13; 22%), and
      patchy-related macular atrophy (n = 5; 8%). Of 66 eyes with LCs, 43 eyes (65%)
      showed progression with development of new patchy atrophy (n = 38; 38/43 or 88%)
      and new LCs (n = 7; 16%). Reduction in best-corrected visual acuity (BCVA) was
      associated mainly (all P < 0.001) with the development of CNV or CNV-related
      macular atrophy and enlargement of macular atrophy. CONCLUSIONS: The most
      frequent progression patterns were an extension of peripapillary diffuse atrophy
      to macular diffuse atrophy in diffuse atrophy, enlargement of the original
      atrophic lesion in patchy atrophy, and development of patchy atrophy in LCs. Main
      risk factors for progression were older age, longer axial length, and development
      of PPA.

PMID- 29371012
TI  - Association Between Magnetic Resonance Imaging-Measured Intercondylar Notch
      Dimensions and Anterior Cruciate Ligament Injury: A Meta-analysis.
AB  - PURPOSE: To explore the association between the magnetic resonance imaging (MRI)
      measured intercondylar notch dimensions, including the intercondylar notch width
      (NW) and intercondylar notch width index (NWI), and the risk of anterior cruciate
      ligament (ACL) injury by performing a meta-analysis of studies that relied on the
      multiplanar imaging and soft-tissue visualization strengths of MRI. METHODS: The
      MEDLINE, Embase, and SportDiscus databases were searched from inception to March
      2017. Observational studies reporting on the associations of the NWI and NW with
      ACL injury were retrieved. A random-effects model was used to calculate the
      overall weighted mean difference (WMD) between the ACL injury group and control
      group. RESULTS: A total of 20 studies were included in this meta-analysis. The
      combined data showed that subjects with ACL injury, as compared with the control
      group, had a significantly decreased NW (pooled WMD, -1.53 [95% confidence
      interval, -1.81 to -1.25]; P < .00001) and NWI (pooled WMD, -0.02 [95% confidence
      interval, -0.03 to -0.01]; P < .00001). Similar findings were observed in
      subgroup analyses in terms of different injury mechanisms. No significant
      difference in NWI was found in the axial view. A significantly decreased NW and
      NWI were found in other plane views. The sensitivity analyses after the exclusion
      of studies enrolling only athletes or skeletally immature subjects reached
      similar outcomes. The Begg rank correlation test showed no publication bias.
      CONCLUSIONS: With the accumulation of evidence, this meta-analysis concluded that
      the NW and/or NWI measured by MRI was significantly lower in ACL-injured patients
      than in control subjects. For persons with a narrow intercondylar notch,
      preventive measures can be prepared for the prevention of ACL injuries. LEVEL OF
      EVIDENCE: Level III, meta-analysis of Level II and III studies.

PMID- 29371013
TI  - Factors Affecting Cost, Outcomes, and Tendon Healing After Arthroscopic Rotator
      Cuff Repair.
AB  - BACKGROUND: The purpose of this study was to simultaneously examine costs,
      functional outcomes, and tendon healing after arthroscopic rotator cuff repair.
      METHODS: This was a retrospective, single-surgeon, single-hospital study. Pre-
      and postoperative Simple Shoulder Test (SST), visual analog scale (VAS) pain, and
      American Shoulder and Elbow Surgeons (ASES) scores, and postoperative magnetic
      resonance images (MRIs) were obtained. Direct costs were derived using a unique,
      validated tool. Costs included overall total direct cost, which included facility
      use costs, medication costs, supply costs, and other ancillary costs. RESULTS: 85
      patients had a minimum 1-year follow-up of functional outcomes (mean of 1.24
      years, range 1-3.2 years) and 56 of 85 (66%) had postoperative MRI healing data
      at an average follow-up of 1.3 years (range 1-3.2 years). Increased direct cost
      was associated with ASA class III (P < .001) compared with ASA class I,
      procedures performed at the main operative room (P = .017) compared with those at
      the surgical center, single-row repair (P < .001) compared with double-row
      repair, medium and large tear sizes (P < .001 and P = .001) compared with small
      tear, and increased number of anchors (P <= .001 or P < .039 for each
      additional). Arthroscopic biceps tenodesis was associated with decreased
      improvement in SST, VAS-pain, and ASES scores (P < .001, .012, and .024), whereas
      infraspinatus atrophy and large/massive tear size was associated with decreased
      improvement in ASES scores (P = .03). Obesity (P = .004) and smoking (P = .034)
      were associated with greater improvement in VAS-pain scores as these were
      associated with decreased preoperative scores. Seventy percent of tears healed.
      CONCLUSIONS: Within our study, factors that increased direct costs were outcome
      neutral, and factors that improved outcome were cost neutral. LEVEL OF EVIDENCE:
      Level IV, retrospective.

PMID- 29371014
TI  - Rotavirus strain distribution in Ghana pre- and post- rotavirus vaccine
      introduction.
AB  - BACKGROUND: Ghana introduced the monovalent rotavirus vaccine (Rotarix) into its
      national paediatric vaccination programme in May2012. Vaccine introduction was
      initiated nationwide and achieved >85% coverage within a few months. Rotavirus
      strain distribution pre- and post-RV vaccine introduction is reported. METHODS:
      Stool samples were collected from diarrhoeic children <5 years of age
      hospitalized between 2009 and 2016 at sentinel sites across Ghana and analyzed
      for the presence of group A rotavirus by enzyme immunoassay. Rotavirus strains
      were characterized by RT-PCR and sequencing. RESULTS: A total of 1363 rotavirus
      EIA-positive samples were subjected to molecular characterization. These were
      made up of 823 (60.4%) and 540 (39.6%) samples from the pre- and post-vaccine
      periods respectively. Rotavirus VP7 genotypes G1, G2 and G3, and VP4 genotypes
      P[6] and P[8] constituted more than 65% of circulating G and P types in the pre
      vaccine period. The common strains detected were G1P[8] (20%), G3P[6] (9.2%) and
      G2P[6] (4.9%). During the post-vaccine period, G12, G1 and G10 genotypes,
      constituted more than 65% of the VP7 genotypes whilst P[6] and P[8] made up more
      than 75% of the VP4 genotypes. The predominant circulating strains were G12P[8]
      (26%), G10P[6] (10%) G3P[6] (8.1%) and G1P[8] (8.0%). We also observed the
      emergence of the unusual rotavirus strain G9P[4] during this period. CONCLUSION:
      Rotavirus G1P[8], the major strain in circulation during the pre-vaccination era,
      was replaced by G12P[8] as the most predominant strain after vaccine
      introduction. This strain replacement could be temporary and unrelated to vaccine
      introduction since an increase in G12 was observed in countries yet to introduce
      the rotavirus vaccine in West Africa. A continuous surveillance programme in the
      post-vaccine era is necessary for the monitoring of circulating rotavirus strains
      and the detection of unusual/emerging genotypes.

PMID- 29371015
TI  - Reactive vaccination as a control strategy for pneumococcal meningitis outbreaks
      in the African meningitis belt: Analysis of outbreak data from Ghana.
AB  - Streptococcus pneumoniae is increasingly recognised as an important cause of
      bacterial meningitis in the African meningitis belt. The World Health
      Organization sets guidelines for response to outbreaks of meningococcal
      meningitis, but there are no current guidelines for outbreaks where S. pneumoniae
      is implicated. We aimed to evaluate the impact of using a similar response to
      target outbreaks of vaccine-preventable pneumococcal meningitis in the meningitis
      belt. Here, we adapt a previous model of reactive vaccination for meningococcal
      outbreaks to estimate the potential impact of reactive vaccination in a recent
      pneumococcal meningitis outbreak in the Brong-Ahafo region of central Ghana using
      weekly line list data on all suspected cases over a period of five months. We
      determine the sensitivity and specificity of various epidemic thresholds and
      model the cases and deaths averted by reactive vaccination. An epidemic threshold
      of 10 suspected cases per 100,000 population per week performed the best,
      predicting large outbreaks with 100% sensitivity and more than 85% specificity.
      In this outbreak, reactive vaccination would have prevented a lower number of
      cases per individual vaccinated (approximately 15,300 doses per case averted)
      than previously estimated for meningococcal outbreaks. Since the burden of death
      and disability from pneumococcal meningitis is higher than that from
      meningococcal meningitis, there may still be merit in considering reactive
      vaccination for outbreaks of pneumococcal meningitis. More outbreak data are
      needed to refine our model estimates. Whatever policy is followed, we emphasize
      the importance of timely laboratory confirmation of suspected cases to enable
      appropriate decisions about outbreak response.

PMID- 29371016
TI  - High glucose up-regulates microRNA-34a-5p to aggravate fibrosis by targeting
      SIRT1 in HK-2 cells.
AB  - Tubulointerstitial fibrosis (TIF) is crucial in the development of renal fibrosis
      in diabetic nephropathy(DN). Previous data shows that SIRT1 plays an important
      role on fibrosis, but the effect on TIF in DN and underlying mechanisms remains
      uncertain. In this study, we evaluated the vital role of SIRT1 and identified
      SIRT1 as a downstream target gene of microRNA-34a-5p (miR-34a-5p) in TIF of DN.
      The result revealed that expression of miR-34a-5p, fibronectin(FN),collagen type
      I (COL1) and transforming growth factor beta1 (TGF-beta1) were up-regulated
      accompanied by the corresponding down-regulation of SIRT1 in renal tissues of
      high fat diet and streptozotocin(HFD/STZ)induced diabetic mice with DN, and that
      the SIRT1 mRNA level was negatively correlated with miR-34a-5p expression in high
      glucose stimulated human proximal tubule cell line(HK-2) cells. We then
      demonstrated that overexpression of SIRT1 reduced, whereas small interfering RNA
      targeting SIRT1 enhanced the expressions of TGF-beta1 and fibrosis-related genes
      including FN and COL1 in HK-2 cells. Furthermore, we identified that miR-34a-5p
      directly suppressed SIRT1 to increase the profibrogenic effects of TGFbeta1
      through targeting the 3'untranslated region of SIRT1. The functional correlation
      of miR-34a-5p induced SIRT1 decrease was supported by overexpression and
      inhibition of miR-34a-5p in HK-2 cells. All the results reveal that SIRT1 which
      is vital in the evolution of renal TIF in DN can be directly suppressed by miR
      34a-5p, and suggest that miR-34a-5p is a new target for DN treatment.

PMID- 29371018
TI  - Hepatitis B virus reactivation after direct-acting antivirals for chronic
      hepatitis C infection.

PMID- 29371017
TI  - Hepatitis B virus reactivation during direct-acting antiviral therapy for
      hepatitis C: a systematic review and meta-analysis.
AB  - BACKGROUND: Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus
      (HCV) infection might pose a risk for hepatitis B virus (HBV) reactivation in
      patients coinfected with chronic or resolved HBV infection. The need for HBV
      antiviral prophylaxis during DAA treatment remains controversial. We aimed to
      analyse the absolute risk of HBV reactivation in patients with active or resolved
      HBV infection treated with DAAs for HCV infection. METHODS: For this systematic
      review and meta-analysis, we searched PubMed, Ovid MEDLINE, the Cochrane Central
      Register of Controlled Trials, and Web of Science from Oct 1, 2010, to Sept 30,
      2017, to identify studies of patients with chronic or resolved HBV infection at
      baseline treated with DAAs for chronic HCV infection. Conference proceedings,
      abstract books, and references from relevant reviews were also examined for
      potential studies. Two independent researchers extracted data and assessed
      quality and risk of bias. Data were pooled by use of random-effects models. The
      primary outcome was HBV reactivation defined by standardised nomenclature. This
      study is registered with PROSPERO, number CRD42017065882. FINDINGS: We identified
      17 observational studies involving 1621 patients with chronic (n=242) or resolved
      (n=1379) HBV infection treated with different DAAs. The pooled proportion of
      patients who had HBV reactivation was 24% (95% CI 19-30) in patients with chronic
      HBV infection and 1.4% (0.8-2.4) in those with resolved HBV infection. In
      patients with chronic HBV infection, the pooled proportion of patients with HBV
      reactivation-related hepatitis was 9% (95% CI 5-16) and the relative risk (RR) of
      HBV-reactivation-related hepatitis was significantly lower in patients with HBV
      DNA below the lower limit of quantification at baseline than in those with
      quantifiable HBV DNA (RR 0.17, 95% CI 0.06-0.50; p=0.0011). Three major clinical
      events related to HBV reactivation in patients with chronic HBV infection were
      reported (one patient had liver decompensation and two had liver failure, one of
      whom required liver transplantation). In patients with resolved HBV infection, no
      HBV-reactivation-related hepatitis was reported. INTERPRETATION: HBV reactivation
      occurs frequently in patients with chronic HBV and HCV coinfection receiving DAA
      therapy but is rare among patients with resolved HBV infection. Use of antiviral
      prophylaxis might be warranted in patients who test positive for hepatitis B
      surface antigen (HBsAg), particularly those with quantifiable HBV DNA. FUNDING:
      None.

PMID- 29371019
TI  - Stable and sustained release liposomal formulations of celecoxib: In vitro and in
      vivo anti-tumor evaluation.
AB  - Celecoxib (CLX) is a selective COX-2 inhibitor with anticancer potential in a COX
      2 dependent and independent manner. CLX's low water solubility has a dose
      limiting effect on its utilization in cancer treatment. Here, we developed
      liposomal drug delivery systems to allow a systemic administration and increase
      tumor accumulation of CLX based on the enhanced permeability and retention (EPR)
      mechanism. Nine liposomal formulations has been prepared with different
      phospholipid compositions; among them three sets of liposomal formulations were
      selected based on characterization and stability for further studies. Anti-tumor
      effects of CLX-entrapped liposomal formulations were tested in vitro by
      cytotoxicity test and in vivo in BALB/c mice bearing C26 colon carcinoma.
      Biodistribution of liposomal-CLX has been studied by radiolabeling of CLX with
      I125.The selected formulations had average size of about 100 nm, a narrow
      monomodal distribution with storage stability of at least one year at 4  degrees
      C. The HSPC/DSPG/cholesterol/DSPE-PEG2000/CLX (65/10/10/5/10 M ratio) liposomal
      formulation had slowest release profile and greatest antitumor effects in vivo.
      This liposomal I125CLX formulation had a three times more accumulation in tumor
      site in comparison to the free I125CLX. Liposomal CLX may serve as a safe, slow
      release and effective anti-tumor agent and merits further investigation.

PMID- 29371020
TI  - Liquid crystalline drug delivery vehicles for oral and IV/subcutaneous
      administration of poorly soluble (and soluble) drugs.
AB  - Poorly soluble drug molecules often have low bioavailability issues and
      absorption problems in the clinical setting. As the number of poorly soluble
      drugs increases from discovery, developing technologies to enhance their
      solubility, while also controlling their release is one of the many challenges
      facing the pharmaceutical industry today. Liquid crystalline systems,
      nanoparticulate or macro-matrix, self-assemble in the presence of an aqueous
      environment and can provide a solubility enhancement, while also controlling the
      drug release rate. This review examines the fundamentals of liquid crystalline
      systems through the representative literature, concluding with examples of liquid
      crystalline systems in clinical trials development. The review focus is on the
      potential of utilizing liquid crystalline systems for poorly soluble drugs, in
      the areas of oral delivery and IV/subcutaneous, followed by water soluble
      molecules. Key considerations in utilizing liquid crystalline systems advantages
      while also discussing potential areas of key research that may be needed will be
      highlighted.

PMID- 29371021
TI  - The interplay between noncoding RNAs and insulin in diabetes.
AB  - Noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular
      RNAs, regulate various biological processes and are involved in the initiation
      and progression of human diseases. Insulin, a predominant hormone secreted from
      pancreatic beta cells, is an essential factor in regulation of systemic
      metabolism through multifunctional insulin signaling. Insulin production and
      action are tightly controlled. Dysregulations of insulin production and action
      can impair metabolic homeostasis, and eventually lead to the development of
      multiple metabolic diseases, especially diabetes. Accumulating data indicates
      that ncRNAs modulate beta cell mass, insulin synthesis, secretion and signaling,
      and their role in diabetes is dramatically emerging. This review summarizes our
      current knowledge of ncRNAs as regulators of insulin, with particular emphasis on
      the implications of this interplay in the development of diabetes. We outline the
      role of ncRNAs in pancreatic beta cell mass and function, which is critical for
      insulin production and secretion. We also highlight the involvement of ncRNAs in
      insulin signaling in peripheral tissues including liver, muscle and adipose, and
      discuss ncRNA-mediated inter-organ crosstalk under diabetic conditions. A more in
      depth understanding of the interplay between ncRNAs and insulin may afford
      valuable insights and novel therapeutic strategies for treatment of diabetes, as
      well as other human diseases.

PMID- 29371022
TI  - Single cell transcriptome sequencing: A new approach for the study of mammalian
      sex determination.
AB  - Mammalian sex determination is a highly complex developmental process that is
      particularly difficult to study due to the limited number of gonadal cells
      present at the bipotential stage, the large cellular heterogeneity in both testis
      and ovaries and the rapid sex-dependent differentiation processes. Single-cell
      RNA-sequencing (scRNA-seq) circumvents the averaging artifacts associated with
      methods traditionally used to profile bulk populations of cells. It is a powerful
      tool that allows the identification and classification of cell populations in a
      comprehensive and unbiased manner. In particular, scRNA-seq enables the tracing
      of cells along developmental trajectories and characterization of the
      transcriptional dynamics controlling their differentiation. In this review, we
      describe the current state-of-the-art experimental methods used for scRNA-seq and
      discuss their strengths and limitations. Additionally, we summarize the multiple
      key insights that scRNA-seq has provided to the understanding of mammalian sex
      determination. Finally, we briefly discuss the future of this technology, as well
      as complementary applications in single cell -omics in the context of mammalian
      sex determination.

PMID- 29371023
TI  - Selective attention to smoking cues in former smokers.
AB  - Repeated drug use modifies the emotional and cognitive processing of drug
      associated cues. These changes are supposed to persist even after prolonged
      abstinence. Several studies demonstrated that smoking cues selectively attract
      the attention of smokers, but empirical evidence for such an attentional bias
      among successful quitters is inconclusive. Here, we investigated whether
      attentional biases persist after smoking cessation. Thirty-eight former smokers,
      34 current smokers, and 29 non-smokers participated in a single experimental
      session. We used three measures of attentional bias for smoking stimuli: A visual
      probe task with short (500ms) and long (2000ms) picture stimulus durations, and a
      modified Stroop task with smoking-related and neutral words. Former smokers and
      current smokers, as compared to non-smokers, showed an attentional bias in visual
      orienting to smoking pictures in the 500ms condition of the visual probe task.
      The Stroop interference index of smoking words was negatively related to nicotine
      dependence in current smokers. Former smokers and mildly dependent smokers, as
      compared to non-smokers, showed increased interference by smoking words in the
      Stroop task. Neither current nor former smokers showed an attentional bias in
      maintained attention (2000ms visual probe task). In conclusion, even after
      prolonged abstinence smoking cues retain incentive salience in former smokers,
      who differed from non-smokers on two attentional bias indices. Attentional biases
      in former smokers operate mainly in early involuntary rather than in controlled
      processing, and may represent a vulnerability factor for relapse. Therefore,
      smoking cessation programs should strengthen self-control abilities to prevent
      relapses.

PMID- 29371025
TI  - Home Non-Invasive Ventilation for COPD: How, Who and When?
AB  - Patients with chronic obstructive pulmonary disease (COPD) and chronic
      respiratory failure have high levels of morbidity and mortality. The clinical
      efficacy of long term home oxygen therapy has been well documented in this
      patient group but despite the efficacy of non-invasive ventilation (NIV) during
      acute decompensated respiratory failure the addition of home NIV has been
      associated with equivocal results. The physiological efficacy of home NIV to
      improve gas exchange in chronic stable hypercapnic respiratory failure has been
      proven in small studies but larger clinical trials failed to translate this into
      clinical efficacy. Criticisms of early clinical trials include the use of
      marginally hypercapnic patients and failure to demonstrate effective delivery of
      home NIV. When considering recent trial data it is important to clearly evaluate
      the patient phenotype and timing and delivery of NIV. Recent data supports the
      delivery of home NIV in patients with chronic hypercapnia (PaCO2>7kPa or 50mmHg)
      and the frequent or infrequent exacerbator phenotype. Importantly in the frequent
      exacerbator the timing of the assessment needs to be in the recovery phase, 2-4
      weeks after resolution of acute acidosis, to delineate transient from persistent
      hypercapnia. In patient with persistent hypercapnia NIV must be titrated to
      achieve control of sleep disordered breathing with the aim of improving daytime
      respiratory failure. Furthermore there are observational data to support the use
      of home positive airway pressure therapy (NIV or continuous positive airway
      pressure; CPAP) in patients with COPD and obstructive sleep apnoea (OSA) both
      with and without hypercapnia.

PMID- 29371026
TI  - Olfactory identification deficit and its relationship with hedonic traits in
      patients with first-episode schizophrenia and individuals with schizotypy.
AB  - OBJECTIVE: Olfactory identification impairments have been consistently found in
      schizophrenia patients. However, few previous studies have investigated this in
      first-episode patients. There are also inconsistent findings regarding olfactory
      identification ability in psychometrically-defined schizotypy individuals. In
      this study, we directly compared the olfactory identification ability of first
      episode schizophrenia patients with schizotypy individuals. The relationship
      between olfactory identification impairments and hedonic traits was also
      examined. METHODS: Thirty-five first-episode schizophrenia patients, 40
      schizotypy individuals as defined by the Chapman's Anhedonia Scales and 40
      demographically matched controls were recruited. The University of Pennsylvania
      Smell Identification Test was administered. Hedonic capacity was assessed using
      the Temporal Experience of Pleasure Scale (TEPS). RESULTS: The results showed
      that both the schizophrenia and schizotypy groups showed poorer olfactory
      identification ability than controls, and the impairment was significantly
      correlated with reduced pleasure experiences. CONCLUSION: Our findings support
      olfactory identification impairment as a trait marker for schizophrenia.

PMID- 29371027
TI  - Atlantic forests to the all Americas: Biogeographical history and divergence
      times of Neotropical Ficus (Moraceae).
AB  - Ficus (Moraceae) is well diversified in the Neotropics with two lineages
      inhabiting the wet forests of this region. The hemiepiphytes of section
      Americanae are the most diversified with c. 120 species, whereas section
      Pharmacosycea includes about 20 species mostly with a terrestrial habit. To
      reconstruct the biogeographical history and diversification of Ficus in the
      Americas, we produced a dated Bayesian phylogenetic hypothesis of Neotropical
      Ficus including two thirds of the species sequenced for five nuclear regions
      (At103, ETS, G3pdh, ITS/5.8S and Tpi). Ancestral range was estimated using all
      models available in Biogeobears and Binary State Speciation and Extinction
      analysis was used to evaluate the role of the initial habit and propagule size in
      diversification. The phylogenetic analyses resolved both Neotropical sections as
      monophyletic but the internal relationships between species in section Americanae
      remain unclear. Ficus started their diversification in the Neotropics between the
      Oligocene and Miocene. The genus experienced two bursts of diversification: in
      the middle Miocene and the Pliocene. Colonization events from the Amazon to
      adjacent areas coincide with the end of the Pebas system (10 Mya) and the
      connection of landmasses. Divergence of endemic species in the Atlantic forest is
      inferred to have happened after its isolation and the opening and consolidation
      of the Cerrado. Our results suggest a complex diversification in the Atlantic
      forest differing between postulated refuges and more instable areas in the South
      distribution of the forest. Finally the selection for initial hemiepiphytic habit
      and small to medium propagule size influenced the diversification and current
      distribution of the species at Neotropical forests marked by the historical
      instability and long-distance dispersal.

PMID- 29371028
TI  - [E.G. Simon in reply to the article by L. Hejl et al.: Vaginal delivery in case
      of breech presentation: impact of a service's incentive. Gynecol Obstet Fertil
      Senol 2017;45(11):596-603].

PMID- 29371029
TI  - Melanoma antigen-D2 controls cell cycle progression and modulates the DNA damage
      response.
AB  - Overexpression of the ubiquitous type II melanoma antigen-D2 (MAGED2) in numerous
      types of cancer suggests that this protein contributes to carcinogenesis, a well
      documented characteristic of other MAGE proteins. Modification of MAGED2
      intracellular localization during cell cycle phases and following treatment with
      camptothecin (CPT) and phosphorylation by ATM/ATR following ionizing irradiation
      led us to investigate the molecular functions of MAGED2 in the cellular response
      to DNA damage. Cell cycle regulators, cell cycle progression, and
      bromodeoxyuridine (BrdU) incorporation were compared between MAGED2-sufficient
      and -depleted U2OS cells following exposure to CPT. At 24 h post-CPT removal,
      MAGED2-depleted cells had lower levels of p21 and p27, and there was an increase
      in S phase BrdU-positive cells with a concurrent decrease in cells in G2. These
      cell cycle modifications were p21-independent, but ATR-, SKP2-, and CDC20
      dependent. Importantly, while MAGED2 depletion reduced CHK2 phosphorylation after
      8 h of CPT treatment, it enhanced and prolonged CHK1 phosphorylation after a 24 h
      recovery period, indicating sustained ATR activation. MAGED2 depletion had no
      impact on cell survival under our experimental conditions. In summary, our data
      indicate that MAGED2 reduced CPT-related replicative stress, suggesting a role
      for this protein in genomic stability.

PMID- 29371024
TI  - From neuroscience to evidence based psychological treatments - The promise and
      the challenge, ECNP March 2016, Nice, France.
AB  - This ECNP meeting was designed to build bridges between different constituencies
      of mental illness treatment researchers from a range of backgrounds with a
      specific focus on enhancing the development of novel, evidence based,
      psychological treatments. In particular we wished to explore the potential for
      basic neuroscience to support the development of more effective psychological
      treatments, just as this approach is starting to illuminate the actions of drugs.
      To fulfil this aim, a selection of clinical psychologists, psychiatrists and
      neuroscientists were invited to sit at the same table. The starting point of the
      meeting was the proposition that we know certain psychological treatments work,
      but we have only an approximate understanding of why they work. The first task in
      developing a coherent mental health science would therefore be to uncover the
      mechanisms (at all levels of analysis) of effective psychological treatments.
      Delineating these mechanisms, a task that will require input from both the clinic
      and the laboratory, will provide a key foundation for the rational optimisation
      of psychological treatments. As reviewed in this paper, the speakers at the
      meeting reviewed recent advances in the understanding of clinical and cognitive
      psychology, neuroscience, experimental psychopathology, and treatment delivery
      technology focussed primarily on anxiety disorders and depression. We started by
      asking three rhetorical questions: What has psychology done for treatment? What
      has technology done for psychology? What has neuroscience done for psychology? We
      then addressed how research in five broad research areas could inform the future
      development of better treatments: Attention, Conditioning, Compulsions and
      addiction, Emotional Memory, and Reward and emotional bias. Research in all these
      areas (and more) can be harnessed to neuroscience since psychological therapies
      are a learning process with a biological basis in the brain. Because current
      treatment approaches are not fully satisfactory, there is an imperative to
      understand why not. And when psychological therapies do work we need to
      understand why this is the case, and how we can improve them. We may be able to
      improve accessibility to treatment without understanding mechanisms. But for
      treatment innovation and improvement, mechanistic insights may actually help.
      Applying neuroscience in this way will become an additional mission for ECNP.

PMID- 29371030
TI  - Regulation on SIRT1-PGC-1alpha/Nrf2 pathway together with selective inhibition of
      aldose reductase makes compound hr5F a potential agent for the treatment of
      diabetic complications.
AB  - (R,E)-N-(3-(2-acetamido-3-(benzyloxy) propanamido)propyl)-2-cyano-3-(4-hydroxy
      phenyl)acrylamide (hr5F) was design-synthesized based on bioactivity focus
      strategy as a potential agent to treat diabetic complicates. With in vitro enzyme
      assay, it is confirmed that hr5F is an effective ALR2 inhibitor with IC50 value
      of 2.60 +/- 0.15 nM, and selectivity index of 86.0 over ALR1, which is a little
      bit better than the reference Epalrestat (Epa). hr5F inhibits the increase of
      ALR2 enzyme activity and expression in human lens epithelial cells (HLECs)
      induced by high glucose. By applying western blot, it was found that hr5F
      alleviates the high glucose-induced superoxide overproduction insults by
      regulating SIRT1-PGC-1alpha/Nrf2 pathway, together with regulating NRF-1, mtTFA,
      Bax/Bcl-2 to ameliorate cell apoptosis. The in vivo effects of hr5F on short term
      streptozocin (STZ)-induced diabetic mice confirm the same functions disclosed in
      vitro. All the evidences support that hr5F may serve as a promising agent in the
      treatment of diabetic complications with close efficacy and broader indication
      than the reference Epa.

PMID- 29371031
TI  - Prominent Canadian Radiologist Receives the Order of Canada.

PMID- 29371033
TI  - Influence of the Super Bowl on the United States birth sex ratio.
AB  - INTRODUCTION: Many factors have been shown to influence the male to female ratio
      at birth (M/T). Celebrations increase M/T nine months later, putatively due to
      elevated coital rates. The Super Bowl (SBS) is consistently held in the first
      Sunday in February. This study was carried out in order to ascertain whether SBS
      results in a rise in M/T nine months later, and whether any such changes are
      influenced by race and census region. METHODS: Births were studied for the period
      2003-2015. Seasonality adjustment was applied in order to identify true outlier
      values over and above those due to natural seasonal M/T variation. RESULTS: This
      study analysed 53,105,069 births. M/T was elevated in all regions, for all races
      for 11/2006, 9/2009, 10/2009, 10/2010, 12/2010, 11/2011, 11/2013 and 12/2013. A
      similar effect is observed in the West Region for all births. For the various
      ethnic groups, the effect is strongest for Whites in regions Northeast, South and
      West, and for Black/African American births in regions Midwest and South.
      DISCUSSION: Events which increase coital activity elevate M/T nine months later
      as M/T follows a U-shaped regression on cycle day of insemination, with male
      conceptions occurring more frequently at the beginning (and end) of the menstrual
      cycle. SBS is a significant annual celebratory event in contemporary American
      culture. It is possible that increased coital rates during this period (perhaps
      due to a combination of celebration and inebriation) may result in the M/T rises
      nine months later observed in this study.

PMID- 29371032
TI  - The DSL ligand APX-1 is required for normal ovulation in C. elegans.
AB  - DSL ligands activate the Notch receptor in many cellular contexts across metazoa
      to specify cell fate. In addition, Notch receptor activity is implicated in post
      mitotic morphogenesis and neuronal function. In C. elegans, the DSL family ligand
      APX-1 is expressed in a subset of cells of the proximal gonad lineage, where it
      can act as a latent proliferation-promoting signal to maintain proximal germline
      tumors. Here we examine apx-1 in the proximal gonad and uncover a role in the
      maintenance of normal ovulation. Depletion of apx-1 causes an endomitotic oocyte
      (Emo) phenotype and ovulation defects. We find that lag-2 can substitute for apx
      1 in this role, that the ovulation defect is partially suppressed by loss of ipp
      5, and that lin-12 depletion causes a similar phenotype. In addition, we find
      that the ovulation defects are often accompanied by a delay of spermathecal
      distal neck closure after oocyte entry. Although calcium oscillations occur in
      the spermatheca, calcium signals are abnormal when the distal neck does not close
      completely. Moreover, oocytes sometimes cannot properly transit through the
      spermatheca, leading to fragmentation of oocytes once the neck closes. Finally,
      abnormal oocytes and neck closure defects are seen occasionally when apx-1 or lin
      12 activity is reduced in adult animals, suggesting a possible post-developmental
      role for APX-1 and LIN-12 signaling in ovulation.

PMID- 29371035
TI  - Eroding Abscess After use of MYNX Closure Device.

PMID- 29371034
TI  - [The cost of obstetric and neonatal care: Case study of the Jason Sendwe hospital
      maternity in Lubumbashi, Democratic Republic of Congo in 2015].
AB  - BACKGROUND: The aim of this study was to determine the user cost for obtaining
      obstetric and neonatal care during childbirth in the Jason Sendwe hospital in the
      city of Lubumbashi, Democratic Republic of Congo. METHODS: We conducted a cross
      sectional study at the maternity of the Jason Sendwe hospital in Lubumbashi,
      reviewing charts and using a questionnaire given to 145 women who gave birth from
      1st August to 30th September 2015. We calculated the cost based on the amounts
      paid by users for obtaining care, expressed in US dollars ($) at an exchange rate
      of 900 Congolese Francs (CDF) for $1. RESULTS: The average age of parturients was
      27+/-6 years (m+/-SD). Nearly 9 out of 10 women were married (84.8%), 24.1% had a
      primary school educational level. The majority (62.1%) had no occupational
      activity and the average monthly income of those employed was $28. Many of their
      spouses were self-employed (36.6%) with an average monthly income of $113.
      Hemorrhage was the most common complication (12.4%); perinatal mortality was
      12.4%, and was only registered in cases of dystocia. Cost of care for eutocic
      delivery was 5 times greater than for complicated vaginal delivery that in turn
      had a 2-fold lower cost than caesarean section. It follows from this study that
      the cost of care for eutocic delivery, complicated vaginal delivery and cesarean
      section was, respectively: 1.4%, 7.5%, and 13.4% of annual household income. In
      general, in case of childbirth, 51%, 40.7%, and 34.4% of households devoted more
      than 5%, 10% and 20% respectively of their annual income to obtain obstetric and
      neonatal care. CONCLUSION: The cost of obstetric and neonatal care is
      catastrophically high for households in Lubumashi. Undoubtedly, those who seek
      hospital care for childbirth must cope with financial problems related to the
      incurred debt. The State should review its healthcare financial policy to ensure
      access to quality care for all.

PMID- 29371036
TI  - Mechanisms of Arterial Calcification: The Role of Matrix Vesicles.
AB  - Vascular calcification is related to vascular diseases, for example,
      atherosclerosis, and its comorbidities, such as diabetes and chronic kidney
      disease. In each condition, a distinctive histological pattern can be recognised
      that may influence technical choices, possible intra-operative complications, and
      procedure outcomes, no matter if the intervention is performed by open or
      endovascular means. This review considers the classification and initiating
      mechanisms of vascular calcification. Dystrophic and metastatic calcifications,
      Monckeberg's calcification, and genetic forms are firstly outlined, followed by
      their alleged initiation mechanisms; these include (a) ineffective macrophage
      efferocytosis; (b) ectopic osteogenesis driven by modified resident or
      circulating osteoprogenitors. As in physiological bio-mineralisation, active
      calcification starts with the deposition of cell derived matrix vesicles into the
      extracellular matrix. To substantiate this belief, an in depth ultra-structural
      documentation of hydroxyapatite crystal deposition on such vesicles is provided
      in an ex-vivo human vascular cell model. Revealing the vesicle composition and
      phenotype in normal and pathological vascular conditions will be essential for
      the development of new therapeutic strategies, in order to prevent and treat
      vascular calcification.

PMID- 29371037
TI  - Predictors of Change in the Ankle Brachial Index with Exercise.
AB  - OBJECTIVE: A 20% or greater decrease in the ankle brachial index (ABI) with
      exercise is suggestive of peripheral artery disease (PAD), and could identify
      patients with an increased mortality risk. The predictors of a change in the ABI
      with exercise have received little attention. METHODS: This was a cross-sectional
      analysis. Two hundred and sixty five participants of the San Diego Population
      Study with a resting ABI between 0.90 and 1.10 performed 50 heel raises and
      immediately had their ABIs measured again. The relationship between the change in
      the ABI with exercise and multiple potential risk prediction variables were
      examined using linear regression. In addition, the categorical percent change in
      the ABI with exercise was analysed by multinomial logistic regression. RESULTS:
      The mean age of participants was 71.8 years, and 80.4% were female. At rest, the
      average ABI was 1.04 (SD 0.04) before and 0.94 (SD 0.13) after exercise; a mean
      decrease of 9.5%. In analyses of ABI change as a continuous variable, higher age,
      any smoking history, and a diagnosis of chronic obstructive pulmonary disease
      (COPD) were associated with a significant decrease in the ABI with exercise (p =
      .01, .04, and .03, respectively). Categorical analyses of the risk factors
      associated with a 20% or greater ABI decrease with exercise confirmed these
      results. Congestive heart failure was associated with an increased ABI with
      exercise (p = .04) in continuous ABI change analyses only. CONCLUSIONS: Older
      age, a positive history of smoking, and a history of COPD were independently and
      significantly associated with a greater ABI decrease with exercise. These risk
      variables may help identify persons with subclinical PAD.

PMID- 29371038
TI  - Reply.

PMID- 29371039
TI  - Invited Commentary.

PMID- 29371040
TI  - Total Artificial Heart Using Bilateral Paracorporeal Pulsatile Ventricular Assist
      Devices in an 8.2-kg Child.
AB  - We present a case report illustrating a novel method of placing a total
      artificial heart in a small child.

PMID- 29371042
TI  - The quantum physics of synaptic communication via the SNARE protein complex.
AB  - Twenty five years ago, Sir John Carew Eccles together with Friedrich Beck
      proposed a quantum mechanical model of neurotransmitter release at synapses in
      the human cerebral cortex. The model endorsed causal influence of human
      consciousness upon the functioning of synapses in the brain through quantum
      tunneling of unidentified quasiparticles that trigger the exocytosis of synaptic
      vesicles, thereby initiating the transmission of information from the presynaptic
      towards the postsynaptic neuron. Here, we provide a molecular upgrade of the Beck
      and Eccles model by identifying the quantum quasiparticles as Davydov solitons
      that twist the protein alpha-helices and trigger exocytosis of synaptic vesicles
      through helical zipping of the SNARE protein complex. We also calculate the
      observable probabilities for exocytosis based on the mass of this quasiparticle,
      along with the characteristics of the potential energy barrier through which
      tunneling is necessary. We further review the current experimental evidence in
      support of this novel bio-molecular model as presented.

PMID- 29371041
TI  - Teratogenic and anticonvulsant effects of zinc and copper valproate complexes in
      zebrafish.
AB  - Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum
      across all types of seizures and epileptic syndromes. Unfortunately,
      approximately 30% of epileptic patients are refractory to the classical AED.
      Metal ions have been frequently incorporated into pharmaceuticals for therapeutic
      or diagnostic purposes and research. In this preliminary study, we assess the
      embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with
      Zn+2 and Cu+2, a derivative of valproic acid and the N-donor ligand in an adult
      zebrafish epileptic seizure model induced by pentylenetetrazole. The most toxic
      complex was [Cu(Valp)2Bipy], in which the LC50 was 0.22 MUM at 48 h post
      fertilization (HPF) and 0.12 MUM at 96 HPF, followed by [Zn(Valp)2Bipy] (LC50 =
      10 MUM). These same metallodrugs ([Cu(Valp)2Bipy] 10 mM/kg and [Zn(Valp)2Bipy] 30
      mM and 100 mM/kg) displayed superior activity, thus reducing the seizure
      intensity by approximately 20 times compared to sodium valproate (175 mM/kg).
      Overall, [Cu(Valp)2Bipy] showed the best anticonvulsant effects. However, because
      of the toxicity of copper, [Zn(Valp)2Bipy] is considered the most promising
      anticonvulsant for future studies.

PMID- 29371043
TI  - Quantitative discoloration assessment of peri-implant soft tissue around zirconia
      and other abutments with different colours: A systematic review and meta
      analysis.
AB  - OBJECTIVES: The implant abutments, which had their own colour, might cause the
      discoloration of peri-implant mucosa. We aimed to appraise trails comparing the
      discoloration of peri-implant soft tissue around zirconia and titanium or golden
      abutments, the tints of which were vastly different. DATA: We included randomized
      controlled trials (RCTs), controlled clinical trials (CCTs), cohort studies with
      patients rehabilitated with zirconia, titanium or golden implant abutments,
      quantitatively comparing the discoloration of peri-implant soft tissue according
      to CIE-Lab colour scale. SOURCES: A systematic search was conducted in PubMed,
      EMBASE, CDSR, and CENTRAL databases without any restriction on September 23,
      2017. "Grey" literatures were also searched. A manual search was carried out as
      well. STUDY SELECTION: Of 584 articles initially retrieved, eight were eligible
      for inclusion. After data extraction, meta-analyses with mean differences (MDs)
      and their 95% confidence intervals (CIs) were employed. Moreover, the risk of
      bias within or across studies was assessed by Cochrane Collaboration's tool for
      assessing risk, the Newcastle-Ottawa scale, funnel plots, or Egger's test.
      RESULTS: Four RCTs and four cohort studies were included. Soft-tissue
      discoloration around zirconia abutments was significantly less likely compared to
      that around titanium abutments (MD = -1.84; 95% CI = -3.62 to -0.07; P = 0.04 <
      0.05) or golden abutments (MD = -0.90; 95% CI = -1.60 to -0.20; P = 0.01 < 0.05).
      CONCLUSIONS: Zirconia abutments with white tint compared to grey titanium or
      golden abutments seem to restore a more appropriate colour match between peri
      implant mucosa and natural teeth. CLINICAL SIGNIFICANCE: Based on the present
      evidence, the "nature-like" zirconia abutments should be applied more often in
      the clinic. PROSPERO REGISTRATION NUMBER: CRD42017075930.

PMID- 29371044
TI  - D-Dimer and thrombus burden in acute pulmonary embolism.
AB  - BACKGROUND: Thrombus burden in pulmonary embolism (PE) is associated with higher
      D-Dimer-levels and poorer prognosis. We aimed to investigate i) the influence of
      right ventricular dysfunction (RVD), deep venous thrombosis (DVT), and high-risk
      PE-status on D-Dimer-levels and ii) effectiveness of D-Dimer to predict RVD in
      normotensive PE patients. METHODS: Overall, 161 PE patients were analyzed
      retrospectively, classified in 5 subgroups of thrombus burden according to
      clinical indications and compared regarding D-Dimer-levels. Linear regression
      models were computed to investigate the association between D-Dimer and the
      groups. In hemodynamically stable PE patients, a ROC curve was calculated to
      assess the effectiveness of D-Dimer for predicting RVD. RESULTS: Overall, 161
      patients (60.9% females, 54.0% aged >70 years) were included in this analysis.
      The D-Dimer-level was associated with group-category in a univariate linear
      regression model (beta 0.050 (95%CI 0.002-0.099), P = .043). After adjustment for
      age, sex, cancer, and pneumonia in a multivariate model we observed an
      association between D-Dimer and group-category with borderline significance (beta
      0.047 (95%CI 0.002-0.096), P = .058). The Kruskal-Wallis test demonstrated that D
      Dimer increased significantly with higher group-category. In 129 normotensive
      patients, patients with RVD had significantly higher D-Dimer values compared to
      those without (1.73 (1.11/3.48) vs 1.17 (0.65/2.90) mg/l, P = .049). A ROC curve
      showed an AUC of 0.61, gender non-specific, with calculated optimal cut-off of
      1.18 mg/l. Multi-variate logistic regression model confirmed an association
      between D-Dimer >1.18 mg/l and RVD (OR2.721 (95%CI 1.196-6.190), P = .017).
      CONCLUSIONS: Thrombus burden in PE is related to elevated D-Dimer levels, and D
      Dimer values >1.18 mg/l were predictive for RVD in normotensive patients. D-Dimer
      levels were influenced by DVT, but not by cancer, pneumonia, age, or renal
      impairment.

PMID- 29371045
TI  - Pediatric emergency department triage-based pain guideline utilizing intranasal
      fentanyl: Effect of implementation.
AB  - BACKGROUND: Pain management guidelines in the emergency department (ED) may
      reduce time to analgesia administration (TTA). Intranasal fentanyl (INF) is a
      safe and effective alternative to intravenous opiates. The effect of an ED pain
      management guideline providing standing orders for nurse-initiated administration
      of intranasal fentanyl (INF) is not known. The objective of this study was to
      determine the impact of a pediatric ED triage-based pain protocol utilizing
      intranasal fentanyl (INF) on time to analgesia administration (TTA) and patient
      and parent satisfaction. METHODS: This was a prospective study of patients 3-17
      years with an isolated orthopedic injury presenting to a pediatric ED before and
      after instituting a triage-based pain guideline allowing for administration of
      INF by triage nurses. Our primary outcome was median TTA and secondary outcomes
      included the proportion of patients who received INF for pain, had unnecessary IV
      placement, and patient and parent satisfaction. RESULTS: We enrolled 132
      patients; 72 pre-guideline, 60 post-guideline. Demographics were similar between
      groups. Median TTA was not different between groups (34.5 min vs. 33 min, p =
      .7). Utilization of INF increased from 41% pre-guideline to 60% post-guideline (p
      = .01) and unnecessary IV placement decreased from 24% to 0% (p = .002). Patients
      and parents preferred the IN route for analgesia administration. CONCLUSION: A
      triage-based pain protocol utilizing INF did not reduce TTA, but did result in
      increased INF use, decreased unnecessary IV placement, and was preferred by
      patients and parents to IV medication. INF is a viable analgesia alternative for
      children with isolated extremity injuries.

PMID- 29371047
TI  - Intracellular glutathione-depleting polymeric micelles for cisplatin prodrug
      delivery to overcome cisplatin resistance of cancers.
AB  - The intrinsic or acquired cisplatin resistance of cancer cells frequently limits
      the final therapeutic efficacy. Detoxification by the high level of intracellular
      glutathione (GSH) plays critical roles in the majority of cisplatin-resistant
      cancers. In this report, we designed an amphiphilic diblock copolymer composed of
      poly(ethylene glycol) (PEG) and polymerized phenylboronic ester-functionalized
      methacrylate (PBEMA), PEG-b-PBEMA, which can self-assemble into micelles in
      aqueous solutions to load hydrophobic cisplatin prodrug (Pt(IV)). Pt(IV)-loaded
      PEG-b-PBEMA micelles (PtBE-Micelle) reverse cisplatin-resistance of cancer cells
      through improving cellular uptake efficiency and reducing intracellular GSH
      level. We found that the cellular uptake amount of platinum from PtBE-Micelle was
      6.1 times higher than that of free cisplatin in cisplatin-resistant human lung
      cancer cells (A549R). Meanwhile, GSH concentration of A549R cells was decreased
      to 32% upon treatment by PEG-b-PBEMA micelle at the phenyl borate-equivalent
      concentration of 100MUM. PtBE-Micelle displayed significantly higher cytotoxicity
      toward A549R cells with half maximal inhibitory concentration (IC50) of cisplatin
      equivalent 0.20MUM compared with free cisplatin of 33.15MUM and Pt(IV)-loaded PEG
      b-poly(epsilon-caprolactone) micelles of cisplatin-equivalent 0.75MUM. PtBE
      Micelle can inhibit the growth of A549R xenograft tumors effectively.
      Accordingly, PEG-b-PBEMA micelles show great potentials as drug delivery
      nanocarriers for platinum-based chemotherapy toward cisplatin-resistant cancers.

PMID- 29371046
TI  - Preparation of amorphous indomethacin nanoparticles by aqueous wet bead milling
      and in situ measurement of their increased saturation solubility.
AB  - The aim of this study was to prepare amorphous indomethacin nanoparticles in
      aqueous media and to determine in situ their increased saturation solubility and
      dissolution rate. Drug nanosuspensions with a Z-average of ~300 nm were prepared
      by wet media milling and afterwards freeze-dried. The drug solid state was
      analyzed by DSC, XRD and FTIR before and after the milling process. Milling of
      amorphous indomethacin with polyvinylpyrrolidone (PVP) as stabilizer resulted in
      an amorphous nanosuspension which could not be redispersed in the nanosize range
      after freeze-drying. The combination of PVP and poloxamer 407 resulted in
      crystalline nanoparticles: poloxamer 407, a polymer with high molecular weight,
      competed with PVP for surface coverage, and hindered the interaction between PVP
      and indomethacin. This indicated the importance of sufficient drug-PVP
      interactions on the drug particle surface for amorphous state stabilization.
      Redispersable amorphous indomethacin nanoparticles were obtained by combining the
      anti-recrystallization effect of PVP with the particle size stabilization
      provided by sodium dodecyl sulfate. Solubility studies were performed in situ.
      The solubility of crystalline micronized indomethacin of 6.7 +/- 1.3 ug/mL was
      increased up to 17.3 +/- 2.8 ug/mL by its amorphization, with a factor of
      increase of 2.6. Indomethacin amorphization increased its dissolution rate by a
      factor of 30. Indomethacin nanocrystals resulted in an increased solubility of
      2.6 times, with a solubility of 17.2 +/- 0.4 ug/mL. The highest increase was
      obtained with amorphous indomethacin nanoparticles with a solubility of 35 +/-
      1.6 ug/mL and 5.2 times higher than the solubility of the original indomethacin.
      Amorphous indomethacin nanoparticles resulted in the highest dissolution rate,
      which increased from 0.003 ug/(mL s) to 2.328 ug/(mL s). The synergistic effect
      obtained by the combination of nanosize and amorphous solid state was
      demonstrated.

PMID- 29371048
TI  - Serum microRNA screening and functional studies reveal miR-483-5p as a potential
      driver of fibrosis in systemic sclerosis.
AB  - OBJECTIVE: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed
      as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we
      investigated the miRNA signature in the serum of systemic sclerosis (SSc)
      patients and we further assessed their expression in early stages of the disease.
      METHODS: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients
      as compared to 9 healthy controls by using an Openarray platform. Three miRNAs
      were examined in an additional cohort of 107 SSc patients and 24 healthy donors
      by single qPCR. MiR-483-5p expression was further analysed in the serum of
      patients with localized scleroderma (LoS) (n = 22), systemic lupus erythematosus
      (SLE) (n = 33) and primary Sjogren's syndrome (pSS) (n = 23). The function of miR
      483-5p was examined by transfecting miR-483-5p into primary human dermal
      fibroblasts and pulmonary endothelial cells. RESULTS: 30 miRNAs were
      significantly increased in patients with SSc. Of these, miR-483-5p showed
      reproducibly higher levels in an independent SSc cohort and was also elevated in
      patients with preclinical-SSc symptoms (early SSc). Notably, miR-483-5p was not
      differentially expressed in patients with SLE or pSS, whereas it was up-regulated
      in LoS, indicating that this miRNA could be involved in the development of skin
      fibrosis. Consistently, miR-483-5p overexpression in fibroblasts and endothelial
      cells modulated the expression of fibrosis-related genes. CONCLUSIONS: Our
      findings showed that miR-483-5p is up-regulated in the serum of SSc patients,
      from the early stages of the disease onwards, and indicated its potential
      function as a fine regulator of fibrosis in SSc.

PMID- 29371049
TI  - TH17 cell plasticity: The role of dendritic cells and molecular mechanisms.
AB  - Upon interaction with dendritic cells (DCs), naive CD4 T cells differentiate into
      distinct subsets and orchestrate the development of a physiological immune
      response. When uncontrolled by cellular and molecular mechanisms, CD4 T cells can
      also lead to immune mediated inflammatory diseases (IMIDs). Initially, these
      distinct CD4 T-cell subsets were defined according to the expression of a limited
      number of cytokines. Later it was revealed that CD4 T cells can acquire much more
      complex functional phenotypes than previously thought. Experimental data showed
      that the CD4 T-cell subset TH17 can secrete IFN-gamma and IL-4, which are
      signature molecules of other T-cell subsets. Furthermore, some TH17 cells can
      also explore an anti-inflammatory fate and participate in the resolution of the
      immune response. A more flexible theory has therefore evolved with the scope to
      better represent the plastic biology of CD4 T cells. In this context, several
      aspects still remain unclear. The goal of this review is to discuss the role of
      extrinsic and intrinsic cellular and molecular mechanisms, which can drive the
      plasticity of TH17 cells. In particular, we will outline the role of DCs and the
      function of transcriptional factors in shaping the fate of TH17 cells towards
      either a pathogenic or a regulatory phenotype. Finally, we will discuss whether
      TH17 cell plasticity could be a target for new therapies for IMIDs. We indeed
      envision that when the cellular and molecular mechanisms controlling TH17
      plasticity are known, new therapies, which aim to reset the immune system, will
      be developed. This will be achieved by either selectively depleting only the
      pathogenic TH17 cells or, if possible, re converting these cells from pathogenic
      to regulatory. This will overcome the challenge posed by the immune suppressive
      side effects caused by the current therapies, which impair the function of CD4
      cells or delete all of them, to the detriment of the patient.

PMID- 29371050
TI  - Laparoscopic transabdominal preperitoneal approach for giant inguinal hernias.
AB  - BACKGROUND: Many surgical techniques have been developed to treat inguinal
      hernia. In recent years, the laparoscopic transabdominal preperitoneal (TAPP)
      approach has been widely performed to repair inguinal hernia. Giant inguinal
      hernia (GIH) is an extremely rare disease that is a challenge for general
      surgeons. GIH appears when patients neglect the treatment for many years and it
      is defined as an inguinal hernia that extends below the midpoint of inner thigh
      in standing position. According to previous publications, the Lichtenstein
      tension-free hernioplasty is recommended to repair GIH. In this article, we
      describe consecutive four cases of GIH repaired via the TAPP approach. METHODS:
      From April 2015 to March 2017, 200 patients underwent hernioplasty against
      inguinal hernia at our hospital. Inguinal hernias were treated via the TAPP
      approach in principle. We performed hernioplasty via the TAPP approach in all 4
      patients (2%) who met the definition of Type 1 GIH. Demographic information,
      maximum diameter of hernia sac, hernia orifice size, and surgical data were
      obtained. RESULTS: The mean operative time was 135 min. No intraoperative
      complications were encountered. All patients could walk from postoperative day 1
      and were discharged home early, but they all had scrotal seromas. Three patients
      did not need puncture or drainage, but one of them required puncture. All seromas
      disappeared within 6 months. There was no recurrence in the 8- to 24-month follow
      up. CONCLUSION: The TAPP approach is a feasible, safe therapeutic option that may
      reduce wound size and pain following surgical treatment of Type 1 GIH.

PMID- 29371051
TI  - Effects of quercitrin on bacterial translocation in a rat model of experimental
      colitis.
AB  - BACKGROUND: This study aimed to analyze the effects of quercitrin, which has anti
      inflammatory properties, on bacterial translocation in inflammatory bowel
      diseases by using an experimental colitis model. METHODS: Forty male Wistar
      Albino rats were used in the study. Rats were divided into 4 groups (control,
      colitis, treatment 1 and 2 groups). The rats in the control group were given
      normal drinking water. In the colitis group, colitis was induced by 5% DSS in
      drinking water. The control and colitis groups underwent operation on Day 7. In
      the 2 treatment groups, 5% DSS was added to drinking water for the first 7 days
      and the groups were treated with quercitrin at the doses of 1 and 5 mg/kg/day for
      the following 10 days. Treatment groups operated on Day 18. Blood samples were
      taken for blood culture and left colectomy was performed. The inflammation in the
      colon was macroscopically and microscopically evaluated and graded. Tissue
      samples were taken (liver, spleen and mesenteric lymph nodes (MLN)) for tissue
      culturing in order to assess bacterial translocation. Tissue myeloperoxidase
      (MPO), serum tumor necrosis factor-alpha (TNF-alpha) and plasma endotoxin levels
      were measured. RESULTS: When the control and colitis groups were compared,
      observed that colitis was induced by DSS (p < 0.05). When the colitis and
      treatment groups were compared, it was found that quercitrin had a significant
      therapeutic effect (p < 0.05). CONCLUSION: In the experimental colitis model
      established by using DSS, treatment with quercitrin resulted in a
      histopathological improvement and reduction in biochemical parameters,
      inflammation and in bacterial translocation (p < 0.05).

PMID- 29371052
TI  - Analytical performance of a commercial multiplex Luminex-based cytokine panel in
      the rat.
AB  - INTRODUCTION: Multiplex immunoassays are an important tool in biomarker research
      during preclinical drug development. However, information regarding analytical
      performance of commercial multiplex assays for animal species is often limited.
      To be able to correctly interpret study results, a fit-for-purpose validation
      approach is recommended. The objective of our study was to provide a realistic
      example of what level of validation can be expected from this type of assay,
      using a rat cytokine panel. METHODS: The analytical performance of a commercial
      Luminex-based multiplex assay comprising IFN-gamma, IL-6, IL-10, IL-12p70, IP-10
      and TNF-alpha was evaluated in Sprague-Dawley rat plasma and serum. Calibration
      curve, working range, precision, accuracy, selectivity, parallelism, dilutional
      linearity, prozone effect and sample stability were assessed. RESULTS: Analytical
      performance in plasma and serum was comparable. Precision and accuracy results
      for all analytes were acceptable with coefficient of variation (CV) and relative
      error (RE) often below 15%, except for serum IL-6. Selectivity results varied per
      analyte with several cytokines showing CV>30% and no single minimum required
      dilution (MRD) could be identified. In addition, some striking differences
      between recombinant and endogenous protein results were observed. A pronounced
      prozone effect was detected for IP-10. Analytes in samples stored at -70 degrees
      C were stable (RE<30%) from 1 up to 6months depending on the analyte. DISCUSSION:
      The results illustrate the challenges encountered during validation of commercial
      animal Luminex-based multiplex assays, revealing analytical limitations such as
      matrix and prozone effects. The Milliplex rat cytokine panel under investigation
      was deemed suitable for relative quantification of exploratory type biomarkers.

PMID- 29371053
TI  - Striatal norepinephrine efflux in l-DOPA-induced dyskinesia.
AB  - l-DOPA remains the primary treatment for Parkinson's disease (PD). Unfortunately,
      its therapeutic benefits are compromised by the development of abnormal
      involuntary movements (AIMs) known as l-DOPA-induced dyskinesia (LID). The
      norepinephrine (NE) system originating in the locus coeruleus is profoundly
      affected in PD and known to influence dopamine (DA) signaling. However, the
      effect of noradrenergic loss on l-DOPA-induced striatal monoamine efflux and
      Parkinsonian motor behavior remains controversial and is frequently overlooked in
      traditional animal models of LID. Thus, the current study sought to determine
      whether degeneration of the DA and/or NE system(s) altered l-DOPA-induced
      striatal monoamine efflux in hemiparkinsonian rats with additional NE loss
      induced by the potent NE-toxin alpha DA beta hydroxylase (DBH)-saporin. Sham-, DA
      , NE-, and dual DA + NE-lesioned rats were treated with l-DOPA (6 mg/kg, s.c.)
      for 2 weeks. Thereafter, l-DOPA-mediated striatal monoamine efflux was measured
      with in vivo microdialysis, and concurrent AIMs testing occurred to determine
      responsiveness to l-DOPA. Noradrenergic lesions exacerbated parkinsonian motor
      deficits but did not significantly alter LID expression or corresponding l-DOPA
      induced striatal monoamine efflux. Interestingly, l-DOPA-induced striatal NE
      efflux rather than DA efflux, corresponded more closely with dyskinesia severity.
      Moreover, marked reductions in striatal NE tissue concentration did not appear to
      impact l-DOPA-induced striatal NE efflux. The current study implicates l-DOPA
      induced striatal NE as an important factor in LID expression and demonstrates the
      importance of developing treatment strategies that co-modulate the NE and DA
      systems.

PMID- 29371054
TI  - Proactive contact lens prescribing - Which approach is more effective?

PMID- 29371055
TI  - Extracellular matrix remodeling and cardiac fibrosis.
AB  - Cardiac fibrosis, characterized by excessive deposition of extracellular matrix
      (ECM) proteins in the myocardium, distorts the architecture of the myocardium,
      facilitates the progression of arrhythmia and cardiac dysfunction, and influences
      the clinical course and outcome in patients with heart failure. This review
      describes the composition and homeostasis in normal cardiac interstitial matrix
      and introduces cellular and molecular mechanisms involved in cardiac fibrosis. We
      also characterize the ECM alteration in the fibrotic response under diverse
      cardiac pathological conditions and depict the role of matricellular proteins in
      the pathogenesis of cardiac fibrosis. Moreover, the diagnosis of cardiac fibrosis
      based on imaging and biomarker detection and the therapeutic strategies are
      addressed. Understanding the comprehensive molecules and pathways involved in ECM
      homeostasis and remodeling may provide important novel potential targets for
      preventing and treating cardiac fibrosis.

PMID- 29371056
TI  - Pneumococcal and influenza vaccine uptake in adults with inflammatory bowel
      disease in France: Results from a web-based study.
AB  - BACKGROUND: Despite specific immunization guidelines for immunocompromised
      patients, there is a dearth of studies on inflammatory bowel disease (IBD)
      population in France. AIMS: To estimate the prevalence and predictors of
      influenza and pneumococcal vaccination rates in a sample of French IBD adults.
      METHODS: An anonymous online survey was submitted to members of several French
      immunocompromised patients' associations during the winter 2016. RESULTS:
      Overall, there were 199/1625 (12%) participants with an IBD. Among these, 32%
      were <30 years old, 85% were male, and 62% were treated with immunosuppressive
      therapy. Self-reported influenza vaccine uptake was 34% (95% CI [28-41]) and 38%
      (95% CI [31-44]) for pneumococcal vaccines. Healthcare provider's (HCP)
      recommendation for vaccination (adjusted OR 12.7 95% CI [5.6-28.8]),
      immunosuppressive therapy (aOR 2.3 [1.1-5.3]), better knowledge of vaccination
      (aOR 3.2 [1.1-9.2]) and favorable attitudes towards vaccination (aOR 3.4 [1.2
      9.5]) were positively associated with influenza vaccine uptake. Vaccine
      recommendation by HCPs was the only independently associated factor with
      pneumococcal vaccines uptake (OR 187.7 [24.8-1422.5]). CONCLUSION: Immunization
      rates in our sample do not reach recommended levels. Factors associated with
      vaccination included high knowledge, favorable attitudes towards vaccination and
      recommendation for vaccination. This underlines the role of health care providers
      in contact with IBD patients.

PMID- 29371057
TI  - Genetic and clinical data predict onset of cryoglobulinemia in HCV patients and
      cryoglobulins clearance.

PMID- 29371058
TI  - Podoconiosis: Nonfilarial endemic elephantiasis.

PMID- 29371060
TI  - Association between unplanned readmission to a different hospital and all-cause
      mortality among older patients with ischemic heart disease: A nationwide claim
      study.

PMID- 29371059
TI  - COPD exacerbations in the emergency department: Epidemiology and related costs. A
      retrospective cohort multicentre study from the Italian Society of Emergency
      Medicine (SIMEU).
AB  - : Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs)
      frequently cause patients with COPD to access the emergency department and have a
      negative impact on the course of the disease. The objectives of our study were:
      1) describing the socio-demographic and clinical characteristics, and the
      clinical management, of patients with AECOPD, when they present to the emergency
      department; and 2) estimating the costs related to the management of these
      patients. We conducted a retrospective cohort study in Italy, collecting data on
      4396 patients, from 34 centres. Patients had a mean (SD) age of 76,6 (10.6)
      years, and 61.2% of them where males. >70% of the patients had a moderate to very
      high comorbidity burden, and heart failure was present in 26.4% of the cohort.
      The 64.6% of patients were admitted to hospital wards, with a mean (SD) length of
      stay of 10.8 (9.8) days. The estimated cost per patient was 2617 ?. CONCLUSIONS:
      Patients attending the ED for an AECOPD are old and present important
      comorbidities. The rate of admission is high, and costs are remarkable.

PMID- 29371063
TI  - Cortical gamma oscillations in isolated dystonia.
AB  - We describe a novel electrophysiologic signal from the motor cortex of patients
      with generalized dystonia - a discrete gamma-band oscillation induced by movement
      and associated with emergence of dystonia. This was observed using both invasive
      and non-invasive methods. This phenomenon is similar to the gamma oscillation
      reported in parkinsonian dyskinesia.

PMID- 29371062
TI  - Mechanistic DNA damage simulations in Geant4-DNA Part 2: Electron and proton
      damage in a bacterial cell.
AB  - We extended a generic Geant4 application for mechanistic DNA damage simulations
      to an Escherichia coli cell geometry, finding electron damage yields and proton
      damage yields largely in line with experimental results. Depending on the
      simulation of radical scavenging, electrons double strand breaks (DSBs) yields
      range from 0.004 to 0.010 DSB Gy-1 Mbp-1, while protons have yields ranging from
      0.004 DSB Gy-1 Mbp-1 at low LETs and with strict assumptions concerning
      scavenging, up to 0.020 DSB Gy-1 Mbp-1 at high LETs and when scavenging is
      weakest. Mechanistic DNA damage simulations can provide important limits on the
      extent to which physical processes can impact biology in low background
      experiments. We demonstrate the utility of these studies for low dose radiation
      biology calculating that in E. coli, the median rate at which the radiation
      background induces double strand breaks is 2.8 * 10-8 DSB day-1, significantly
      less than the mutation rate per generation measured in E. coli, which is on the
      order of 10-3.

PMID- 29371061
TI  - A randomized controlled trial to prevent excessive gestational weight gain and
      promote postpartum weight loss in overweight and obese women: Health In Pregnancy
      and Postpartum (HIPP).
AB  - BACKGROUND: Interventions to prevent excessive gestational weight gain and
      promote postpartum weight loss have yielded modest results, particularly in
      overweight and obese women. OBJECTIVES: To examine the impact of a theory-based
      lifestyle intervention on gestational weight gain, postpartum weight loss, and
      related maternal and child outcomes and to examine race differences in these
      outcomes. DESIGN: A randomized controlled trial (target N=400; 200 intervention,
      200 standard care; 200 African American, 200 white). METHODS: Overweight and
      obese African American and white women <=16weeks gestation are recruited from
      obstetrics and gynecology clinics in South Carolina. Intervention participants
      receive two in-depth counseling sessions (early pregnancy and postpartum),
      telephone counseling, behavioral podcasts, and social media support that target
      weight self-monitoring and increasing physical activity and healthy dietary
      behavior practices, guided by Social Cognitive Theory. Standard care participants
      receive monthly mailings and a matched number of podcasts on non-weight related
      topics. All intervention activities last from <=18weeks gestation to 6months
      after delivery. Gestational weight gain is the primary outcome. Secondary
      outcomes are meeting gestational weight gain guidelines (inadequate, adequate,
      excessive), weekly rate of gestational weight gain, postpartum weight retention,
      physical activity and dietary behaviors, health-related quality of life, and
      offspring adiposity. Participants are assessed at baseline (<=16weeks gestation),
      32weeks gestation, and 6 and 12months postpartum, and offspring are assessed at 6
      and 12months. SUMMARY: HIPP is an innovative study that addresses significant
      gaps in the literature. Primary outcome results are expected in 2019.

PMID- 29371064
TI  - Metagenomic analysis for detecting Fusarium solani in a case of fungal keratitis.
AB  - PURPOSE: To report a difficult-to-identify case of keratitis due to Fusarium
      solani, diagnosed with the help of exhaustive gene analysis. CASE: A 47-year-old
      woman attended our hospital with a refractory corneal ulcer associated with
      contact lens wear in her left eye that had appeared two weeks earlier. On her
      initial visit, slit lamp examination revealed a small double-ringed irregular
      hyphate ulcer in the center of the cornea, which had no epithelial defect,
      suggesting fungal infection. Microscopic visualization and culture of corneal
      scrapings were performed repeatedly, but the results were negative. Despite
      intensive antifungal treatment, infiltration of the cornea worsened and
      therapeutic keratoplasty was performed. Specimens from a corneal button were
      microbiologically and histologically negative for microorganisms. During
      irrigation of the anterior chamber with amphotericin B, aspirated corneal
      infiltrations were submitted for culture and metagenomic analysis. Genes
      belonging to F. solani were identified by metagenomic analysis, and an isolate
      presumed to be a Fusarium species was cultured. Genotypic identification of the
      isolates confirmed F. solani. CONCLUSION: The detection of microorganisms,
      especially fungi, can be extremely difficult. In difficult-to-culture cases,
      metagenomic analysis seems to be a promising technique for the identification of
      microbial pathogens.

PMID- 29371065
TI  - Three cases of Candida fermentati fungemia following hematopoietic stem cell
      transplantation.
AB  - Bloodstream infection with non-Candida albicans Candida species is one of the
      serious complications among patients with hematological malignancies who receive
      long-term prophylactic antifungal agents. Here we describe three cases of Candida
      fermentati (C. fermentati) candidemia after allogeneic stem cell transplantation
      for hematological malignancies. Case 1 is fluconazole-breakthrough C. fermentati
      fungemia, which was well controlled with liposomal amphotericin B. Case 2 and 3
      were caspofungin-breakthrough C. fermentati fungemia. In case 2, blood culture
      turned negative for Candida responding to liposomal amphotericin B. Although in
      vitro susceptibility data for the isolated pathogen suggested the efficacy of
      both caspofungin and liposomal amphotericin B in all three cases, clinically
      liposomal amphotericin B seemed to have been more effective for eradication of
      the pathogen from blood stream. C. fermentati needs to be considered as a
      possible cause for breakthrough candidemia among post-transplant patients with
      prolonged antifungal prophylaxis. Discrepancy between in vitro and in vivo
      susceptibility to antifungals, especially to echinocandins, might provide a clue
      for the optimal choice of antifungals for C. fermentati infections.

PMID- 29371068
TI  - Treating chlamydial infections in pregnancy and preventing adverse birth
      outcomes.

PMID- 29371067
TI  - Chlamydia trachomatis and the risk of spontaneous preterm birth, babies who are
      born small for gestational age, and stillbirth: a population-based cohort study.
AB  - BACKGROUND: Chlamydia trachomatis is one of the most commonly diagnosed sexually
      transmitted infections worldwide, but reports in the medical literature of an
      association between genital chlamydia infection and adverse obstetric outcomes
      are inconsistent. METHODS: The Western Australia Data Linkage Branch created a
      cohort of women of reproductive age by linking records of birth registrations
      with the electoral roll for women in Western Australia who were born from 1974 to
      1995. The cohort was then linked to both chlamydia testing records and the state
      perinatal registry for data on preterm births and other adverse obstetric
      outcomes. We determined associations between chlamydia testing, test positivity,
      and adverse obstetric outcomes using multivariate logistic regression analyses.
      FINDINGS: From 2001 to 2012, 101 558 women aged 15 to 38 years had a singleton
      birth. Of these women, 3921 (3.9%) had a spontaneous preterm birth, 9762 (9.6% of
      101 371 women with available data) had a baby who was small for gestational age,
      and 682 (0.7%) had a stillbirth. During their pregnancy, 21 267 (20.9%) of these
      women had at least one chlamydia test record, and 1365 (6.4%) of those tested
      were positive. Before pregnancy, 19 157 (18.9%) of these women were tested for
      chlamydia, of whom 1595 (8.3%) tested positive for chlamydia. Among all women
      with a test record, after adjusting for age, ethnicity, maternal smoking, and
      history of other infections, we found no significant association between a
      positive test for chlamydia and spontaneous preterm birth (adjusted odds ratio
      1.08 [95% CI 0.91-1.28]; p=0.37), a baby who was small for gestational age (0.95
      [0.85-1.07]; p=0.39), or stillbirth (0.93 [0.61-1.42]; p=0.74). INTERPRETATION: A
      genital chlamydia infection that is diagnosed and, presumably, treated either
      during or before pregnancy does not substantially increase a woman's risk of
      having a spontaneous preterm birth, having a baby who is small for gestational
      age, or having a stillbirth. FUNDING: Australian National Health and Medical
      Research Council.

PMID- 29371066
TI  - International Summit on Laparoscopic Pancreatic Resection (ISLPR) "Coimbatore
      Summit Statements".
AB  - The International Summit on Laparoscopic Pancreatic Resection (ISLPR) was held in
      Coimbatore, India, on 7th and 8th of October 2016 and thirty international
      experts who regularly perform laparoscopic pancreatic resections participated in
      ISPLR from four continents, i.e., South and North America, Europe and Asia. Prior
      to ISLPR, the first conversation among the experts was made online on August
      26th, 2016 and the structures of ISPLR were developed. The aims of ISPLR were; i)
      to identify indications and optimal case selection criteria for minimally
      invasive pancreatic resection (MIPR) in the setting of both benign and malignant
      diseases; ii) standardization of techniques to increase the safety of MIPR; iii)
      identification of common problems faced during MIPR and developing associated
      management strategies; iv) development of clinical protocols to allow early
      identification of complications and develop the accompanying management plan to
      minimize morbidity and mortality. As a process for interactive discussion, the
      experts were requested to complete an online questionnaire consisting of 65
      questions about the various technical aspects of laparoscopic pancreatic
      resections. Two further web-based meetings were conducted prior to ISPLR. Through
      further discussion during ISPLR, we have created productive statements regarding
      the topics of Disease, Implementation, Patients, Techniques, and Instrumentations
      (DIPTI) and hereby publish them as "Coimbatore Summit Statements".

PMID- 29371069
TI  - Growing evidence supports 4CMenB effectiveness.

PMID- 29371070
TI  - Immunogenicity and safety of the multicomponent meningococcal B vaccine (4CMenB)
      in children and adolescents: a systematic review and meta-analysis.
AB  - BACKGROUND: The multicomponent meningococcal serogroup B vaccine (4CMenB) has
      been licensed in more than 35 countries. However, uncertainties remain about the
      lowest number of doses required to induce satisfactory, persistent immune
      responses. We did a systematic review and meta-analysis to provide quantitative
      estimates for the immunogenicity, persistence of immunogenicity, and safety of
      4CMenB vaccine in children and adolescents. METHODS: For this systematic review
      and meta-analyses (proportion, head to head, and network), we searched MEDLINE,
      Scopus, Embase, and ClinicalTrials.gov from database inception to June 30, 2017,
      for randomised trials that compared the immunogenicity or safety of the 4CMenB
      vaccine with its originator meningococcal B recombinant vaccine or routine
      vaccines in children or adolescents. For proportion meta-analyses, we also
      included single arm trials and follow-up studies of randomised controlled trials.
      Trials that assessed immunogenicity against at least one of four Neisseria
      meningitidis serogroup B reference strains (44-76/SL, 5/99, NZ98/254, and M10713)
      and included participants younger than 18 years who had received two or more
      doses of the 4CMenB vaccine were eligible for inclusion. We requested individual
      patient-level data from study authors and extracted data from published reports
      and online trial registries. We did meta-analyses to assess 4CMenB safety and
      immunogenicity against the four reference strains 30 days after a primary
      immunisation course (three doses for children, two doses for adolescents), 30
      days after the primary course plus one booster dose (children only), 6 months or
      more after primary course, and 6 months or more after the booster dose. FINDINGS:
      736 non-duplicate records were screened, and ten randomised trials and eight
      follow-on extension trials on 4CMenB met the inclusion criteria. In intention-to
      treat analyses, the overall proportion of children and adolescents who achieved
      seroconversion 30 days after the primary course of 4CMenB was 92% (95% CI 89-95
      [I2=95%, p<0.0001]) for the 44/76-SL strain, 91% (87-95 [I2=95%, p<0.0001]) for
      the 5/99 strain, 84% (77-90 [I2=97%, p<0.0001]) for the NZ98-254 strain, and 87%
      (68-99 [I2=97%, p<0.0001]) for the M10713 strain. 6 months after the primary
      course, the immunogenicity remained adequate to high against all three tested
      strains (5/99, 44/76-SL, and NZ98/254) in adolescents (>=77%), and against two of
      four strains (5/99 and 44/76-SL) in children (>=67%): the proportion of patients
      who achieved seroconversion substantially declined for M10713 (<50%) and NZ98/254
      (<35%). A booster dose re-enhanced the proportion of patients who achieved
      seroconversion (>=93% for all strains). However, immunogenicity remained high 6
      months after the booster dose for strains 5/99 (95%) and M10713 (75%) only,
      whereas the proportion of patients who achieved seroconversion against strains
      44/76-SL and NZ98/254 returned to similar proportions recorded 6 months after the
      primary course (62% for 44/76-SL, 35% for NZ98/254). The incidence of potentially
      vaccine-related, acute serious adverse events in individuals receiving 4CMenB was
      low (5.4 per 1000 individuals), but was significantly higher than routine
      vaccines (1.2 per 1000 individuals). INTERPRETATION: 4CMenB has an acceptable
      short-term safety profile. The primary course is sufficient to achieve a
      satisfactory immune response within 30 days of vaccination. A booster dose is
      required for children to prolong the protection against strain M10713, and the
      long-term immunogenicity against strain NZ98/254 remains suboptimal. FUNDING:
      None.

PMID- 29371071
TI  - Leukocyte adhesion deficiency-I: A comprehensive review of all published cases.

PMID- 29371072
TI  - Apixaban Causing Leukocytoclastic Vasculitis.

PMID- 29371073
TI  - Skin Testing for Suspected Iodinated Contrast Media Hypersensitivity.
AB  - BACKGROUND: The management of iodinated contrast medium (ICM) hypersensitivity
      has been a matter of debate. Skin testing to identify a subgroup of ICM allergic
      patients has been proposed, in addition to complete avoidance, provocation
      testing, or premedication. OBJECTIVE: The objective of this study was to assess
      the negative predictive value (NPV) of skin testing for ICM. METHODS: Patients
      with a hypersensitivity reaction to ICM who underwent skin testing during a 13.5
      year period at a single center were evaluated for re-exposure to a negatively
      skin-tested ICM. Premedication, consisting of second-generation H1-antihistamines
      twice a day 48 hours before the examination, was advised only for patients with
      mast cell disorder or chronic urticaria who had negative skin tests. RESULTS: A
      total of 597 patients tested for 423 (70.9%) immediate, 118 (19.7%) nonimmediate,
      and 56 (9.4%) hypersensitivity reactions with undetermined chronology were
      included. Eighty (13.4%) patients were skin test positive. Re-exposure to ICM
      occurred in 233 (39.0%) patients and was tolerated in 16 of 17 (94.1%) with at
      least 1 positive skin test and 201 of 216 (93.1%) with all negative skin tests.
      Reaction intensity was similar in 4, milder in 10, unknown in 1, and worse in 1
      patient although this reaction was deemed to be nonallergic in hindsight.
      Premedication was administered in 20.7% of patients and associated with more
      reactions (19.4% vs 5.7%, P = .01). The overall NPV of skin testing for ICM was
      93.1% (95% confidence interval [CI] 89.1% to 96.0%), and for immediate and
      nonimmediate hypersensitivity reactions 94.2% (95% CI 89.6% to 97.2%) and 86.1%
      (95% CI 72.1% to 94.7%), respectively. We cannot exclude some challenges occurred
      with a different than the initial culprit ICM, possibly overestimating the NPV.
      CONCLUSIONS: Skin testing for potential ICM hypersensitivity can identify safe
      alternative(s) for ICM re-exposure especially in patients with an immediate
      hypersensitivity reaction and/or skin test-proven ICM drug allergy. Reactions on
      re-exposure were infrequent, mostly milder, and occurred in some patients despite
      premedication.

PMID- 29371074
TI  - Behavioral risks associated with food allergy management in an urban pediatric
      population.

PMID- 29371075
TI  - Does the temperature of water ingested during exertional-heat stress influence
      gastrointestinal injury, symptoms, and systemic inflammatory profile?
AB  - OBJECTIVES: The study aimed to determine the effects of temperature of ingested
      water during exertional-heat stress on gastrointestinal injury, symptoms and
      systemic inflammatory responses. DESIGN: Randomised cross-over study. METHODS:
      Twelve endurance runners completed 2h running at 60% vO2max in 35 degrees C
      ambient temperature on three separate occasions, consuming 250+/-40mL water
      before and every 15min during running at either 0.4+/-0.4 degrees C (COLD), 7.3+/
      0.8 degrees C (COOL), or 22.1+/-1.2 degrees C (TEMP). Rectal temperature and
      gastrointestinal symptoms were recorded every 10min during exercise. Blood was
      collected pre, immediately and 1h post-exercise to determine plasma intestinal
      fatty-acid binding protein (I-FABP), cortisol, and inflammatory cytokine
      concentrations. RESULTS: Compared to TEMP, COLD and COOL blunted the rise in
      rectal temperature (2.0+/-0.5 degrees C vs. 1.6+/-0.4 degrees C and 1.7+/-0.4
      degrees C, respectively; trial*time, p=0.033). I-FABP increased post-exercise
      (419%, p<0.001), with a trend for reduced I-FABP on COLD and COOL (mean reduction
      460pgmL-1 and 430pgmL-1, respectively), compared to TEMP (p=0.066). No
      differences were observed between trials for gastrointestinal symptoms, albeit a
      trend for increased upper-gastrointestinal symptoms on TEMP (p=0.087) compared to
      COLD and COOL was observed. IL-6, IL-1beta, IL-8, IL-10 and IL-1ra increased post
      exercise (p<0.05); however no differences were observed between trials.
      CONCLUSIONS: COLD and COOL water ingestion during exertional-heat stress
      ameliorates thermoregulatory strain compared to TEMP. However, this appears to
      have no effect on cytokine profile and minimal effect on intestinal epithelial
      injury and gastrointestinal symptoms.

PMID- 29371077
TI  - Keeping it off: the challenge of weight-loss maintenance.

PMID- 29371076
TI  - Prevalence of obesity, hypertension, and diabetes, and cascade of care in sub
      Saharan Africa: a cross-sectional, population-based study in rural and urban
      Malawi.
AB  - BACKGROUND: Sub-Saharan Africa is in rapid demographic transition, and non
      communicable diseases are increasingly important causes of morbidity and
      mortality. We investigated the burden of diabetes, overweight and obesity,
      hypertension, and multimorbidity, their treatment, and their associations with
      lifestyle and other factors in Malawi, a very poor country with a predominantly
      rural-but rapidly growing urban-population, to identify high-risk populations and
      inform appropriate interventions. METHODS: In this cross-sectional, population
      based study, we enrolled all adults (>=18 years) residing in two defined
      geographical areas within Karonga District and Lilongwe city. All adults self
      defining as usually resident in the study areas were eligible, and recruited at
      household level. Participants were interviewed, had anthropometry and blood
      pressure measured, and had fasting blood samples collected. The study outcomes
      were prevalence estimates and risk ratios for diabetes (defined as fasting blood
      glucose of at least 7.0 mmol/L or self-report of a previous diagnosis of
      diabetes), hypertension (systolic blood pressure of at least 140 mm Hg, diastolic
      blood pressure of at least 90 mm Hg, or self-report of current antihypertensive
      medication), overweight (BMI of 25.0-29.9 kg/m2) and obesity (BMI of 30.0 kg/m2
      or more), and multimorbidity (two or more of the above conditions) by location
      specific (urban vs rural), age-specific, and sex-specific groups, calculated
      using negative binomial regression. We used chi2 likelihood ratio tests to assess
      heterogeneity by age, location, and sex. FINDINGS: Between May 16, 2013, and Feb
      8, 2016, we enrolled 15 013 (62%) of 24 367 eligible urban adults in Lilongwe and
      13 878 (88%) of 15 806 eligible rural adults in Karonga District. Overweight and
      obesity, hypertension, and diabetes were highly prevalent, more so in urban
      residents, the less poor, and better educated than in rural, the poorest, and
      least educated participants. 18% of urban men (961 of 5211 participants) and 44%
      (4115 of 9282) of urban women, and 9% (521 of 5834) of rural men and 27% (2038 of
      7497) of rural women were overweight or obese; 16% (859 of 5212), 14% (1349 of
      9793), 13% (787 of 5847), and 14% (1101 of 8025) had hypertension; and 3% (133 of
      3928), 3% (225 of 7867), 2% (84 of 5004), and 2% (124 of 7116) had diabetes,
      respectively. Of 566 participants with diabetes, 233 (41%) were undiagnosed, and
      of 4096 participants with hypertension, 2388 (58%) were undiagnosed. Fewer than
      half the participants on medication for diabetes or hypertension had well
      controlled diabetes (84 [41%] of 207 participants) or blood pressure (440 [37%]
      of 1183 participants). Multimorbidity was highest in urban women (n=519, 7%).
      INTERPRETATION: Overweight and obesity, hypertension, and diabetes are highly
      prevalent in urban and rural Malawi, yet many patients are undiagnosed and
      management is limited. Local-evidence-informed multisectoral, innovative, and
      targeted interventions are needed urgently to manage the already high burden.
      FUNDING: Wellcome Trust.

PMID- 29371078
TI  - NCD risk factors in Malawi: population characteristics matter.

PMID- 29371079
TI  - Schizencephaly in children: A single medical center retrospective study.
AB  - BACKGROUND: The aim of this study was to evaluate the clinical, and neuroimaging
      features, outcomes, and other associated systemic disorders in children with
      schizencephaly at a single medical center in Taiwan. METHODS: We retrospectively
      reviewed the medical records and magnetic resonance images (MRI) of children with
      schizencephaly between January 2000 and December 2014. The MRI findings of
      schizencephaly were recorded along with the presence of associated cerebral
      disorders. Clinical, electroencephalographic and additional systemic disorders
      were also recorded. RESULTS: A total of 21 patients (13 males and 8 females) were
      included in the study. According to the location of schizencephaly, the patients
      were classified into two groups: unilateral (n = 16) and bilateral (n = 5). The
      majority of the patients with neurological deficits were detected before 1 year
      of age, especially in bilateral clefts. The most common initial presentation was
      hemiparesis in unilateral schizencephaly, and seizures in bilateral
      schizencephalies. Ventriculomegaly was the most common associated cerebral
      disorder, and the most common additional systemic disorders included congenital
      heart disease, hydronephrosis, and strabismus. Seventeen patients suffered from
      epileptic seizures with generalized tonic-clonic seizures being the most common.
      Eight patients developed refractory epilepsy. The majority of the patients had
      motor deficits, intellectual disabilities, and language deficits, especially in
      bilateral clefts. CONCLUSIONS: This study demonstrates that the clinical features
      of schizencephaly vary widely, with their severity closely related to the cleft.
      Determining the type, size, and extent of schizencephaly is useful to plan
      management and predict the prognosis.

PMID- 29371080
TI  - Ear Disease Knowledge and Otoscopy Skills Transfer to Real Patients: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To determine which teaching method-otoscopy simulation (OS), web-based
      module (WM), or standard classroom instruction (SI)-produced greater translation
      of knowledge and otoscopy examination skills to real patients. DESIGN: In a
      prospective randomized controlled nonclinical trial, medical students were
      randomized to 1 of 3 interventional arms: (1) OS, (2) WM, or (3) SI. Students
      were assessed at baseline for diagnostic accuracy and otoscopy skills on 5
      volunteer patients (total of 10 ears), followed by the intervention. Testing was
      repeated immediately after intervention on the same patients. Student reported
      confidence in diagnostic accuracy and otoscopy examination were also captured.
      Assessors were blinded to the intervention group, and whether students were pre-
      or post-intervention. SETTING: Clinical Teaching Centre, Queen's University.
      PARTICIPANTS: Twenty-nine participants were initially randomized. Two students
      were unable to attend their specific intervention sessions and withdrew. Final
      group sizes were: OS-10, WM-9, SI-8. Five patients with external/middle ear
      pathologies were voluntarily recruited to participate as testing subjects.
      RESULTS: Baseline diagnostic accuracy and otoscopy clinical skills did not differ
      across the groups. Post-intervention, there were improvements in diagnostic
      accuracy from all groups: OS (127.78%, 2.30 +/- 1.42, p = 0.0006), WM (76.40%,
      1.44 +/- 1.88, p = 0.0499), and SI (100.00%, 1.50 +/- 1.20, p = 0.0093). For
      otoscopy skills, post-intervention improvements were noted from OS (77.00%, 3.85
      +/- 2.55, p < 0.0001) and SI (22.20%, 1.25 +/- 1.20, p = 0.0011), with no
      significant improvement from WM (13.46%, 0.78 +/- 1.92, p = 0.1050). Students
      across all groups reported significantly improved confidence in diagnostic
      accuracy (p < 0.0001) and otoscopy skill (p < 0.0001) after the intervention.
      CONCLUSION: All 3 teaching modalities showed an improvement in diagnostic
      accuracy immediately post-intervention. Otoscopy clinical skills were found to
      have increased only in OS and SI, with the OS group demonstrating the largest
      improvement. Simulation-based medical education in Otolaryngology may provide the
      greatest transfer of medical knowledge and technical skills when evaluated with
      real patients.

PMID- 29371081
TI  - Orthopaedic Surgery Residency Training: Consideration for a Surgical and
      Procedural Skills Competency.
AB  - This perspectives report discusses the need to create a surgical and procedural
      skills competency for orthopedic surgery residency training programs.

PMID- 29371082
TI  - Feasibility of using a bacteriophage-based structural color sensor for screening
      the geographical origins of agricultural products.
AB  - An M13 bacteriophage-based color sensor, which can change its structural color
      upon interaction with a gaseous molecule, was evaluated as a screening tool for
      the discrimination of the geographical origins of three different agricultural
      products (garlic, onion, and perilla). Exposure of the color sensor to sample
      odors induced the self-assembled M13 bacteriophage bundles to swell by the
      interaction of amino acid residues (repeating units of four glutamates) on the
      bacteriophage with the odor components, resulting in a change in the structural
      color of the sensor. When the sensor was exposed to the odors of garlic and onion
      samples, the RGB color changes were considerable because of the strong
      interactions of the odor components such as disulfides with the glutamate
      residues on the sensor. Although the patterns of the color variations were
      generally similar between the domestic and imported samples, some degrees of
      dissimilarities in their intensities were also observed. Although the magnitude
      of color change decreased for perilla, the color change patterns between the two
      groups were somewhat different. With the acquired RGB data, a support vector
      machine was employed to distinguish the domestic and imported samples, and the
      resulting accuracies in the measurements of garlic, onion, and perilla samples
      were 94.1, 88.7, and 91.6%, respectively. The differences in the concentrations
      of the odor components between both groups and/or the presence of specific
      components exclusively in the odor of one group allowed the color sensor-based
      discrimination. The demonstrated color sensor was thus shown to be a potentially
      versatile and simple as an on-site screening tool. Strategies able to further
      improve the sensor performance were also discussed.

PMID- 29371083
TI  - Spontaneously occurring intramural coronary arteriosclerosis in regularly
      slaughtered veal calves and beef cattle: a screening study about prevalence and
      histopathological features.
AB  - OBJECTIVES: Intramural coronary arteriosclerosis has been reported in several
      species, but no systematic studies are currently available in bovine. The present
      study aimed to describe the arteriosclerotic changes in regularly slaughtered
      veal calves and beef cattle. ANIMALS: Twenty-five veal calves (6-9 months old)
      and 17 beef cattle (10-24 months old) housed in intensive livestock farming and
      regularly slaughtered were included in the present study. METHODS: Selected heart
      samples were submitted for histopathological and ultrastructural examination and
      the following parameters were evaluated: intimal hyperplasia, degenerative
      changes of the tunica media, medial hypertrophy/hyperplasia, myocardial fibrosis,
      and myocarditis. Pathological intramural coronary arteries with and without lumen
      narrowing were manually counted in every sample. RESULTS: Intramural coronary
      arteriosclerosis was observed in all the calves and cattle, with similar
      prevalence of fibromuscular/muscular intimal hyperplasia (92% vs 88%),
      degenerative changes of the tunica media (76% vs 71%), and medial
      hypertrophy/hyperplasia (44% vs 59%). The posterior papillary muscle of the left
      ventricle was the myocardial localization significantly more affected in both
      calves (p = 0.0007) and cattle (p = 0.0339). Anitschkow cells were detected in
      the coronary walls of both calves (60%) and cattle (76%). CONCLUSIONS: This is
      the first study that systematically describes spontaneously occurring intramural
      coronary arteriosclerosis in bovine species. Anitschkow cells, whose
      ultrastructural characteristics and localization suggest their potential origin
      from the smooth muscle cells of the tunica media of the arteriosclerotic coronary
      vessels, were also identified.

PMID- 29371084
TI  - Instantaneous wave-free ratio as an alternative to fractional flow reserve in
      assessment of moderate coronary stenoses: A meta-analysis of diagnostic accuracy
      studies.
AB  - BACKGROUND/PURPOSE: Fractional flow reserve (FFR) remains underutilized due to
      practical concerns related to the need for hyperemic agents. These concerns have
      prompted the study of instantaneous wave-free ratio (iFR), a vasodilator-free
      index of coronary stenosis. Non-inferior cardiovascular outcomes have been
      demonstrated in two recent randomized clinic trials. We performed this meta
      analysis to provide a necessary update of the diagnostic accuracy of iFR
      referenced to FFR based on the addition of eight more recent studies and 3727
      more lesions. METHODS: We searched the PubMed, EMBASE, Central, ProQuest, and Web
      of Science databases for full text articles published through May 31, 2017 to
      identify studies addressing the diagnostic accuracy of iFR referenced to
      FFR<=0.80. The following keywords were used: "instantaneous wave-free ratio" OR
      "iFR" AND "fractional flow reserve" OR "FFR." RESULTS: In total, 16 studies
      comprising 5756 lesions were identified. Pooled diagnostic accuracy estimates of
      iFR versus FFR<=0.80 were: sensitivity, 0.78 (95% CI, 0.76-0.79); specificity,
      0.83 (0.81-0.84); positive likelihood ratio, 4.54 (3.85-5.35); negative
      likelihood ratio, 0.28 (0.24-0.32); diagnostic odds ratio, 17.38 (14.16-21.34);
      area under the summary receiver-operating characteristic curve, 0.87; and an
      overall diagnostic accuracy of 0.81 (0.78-0.84). CONCLUSIONS: In conclusion, iFR
      showed excellent agreement with FFR as a resting index of coronary stenosis
      severity without the undesired effects and cost of hyperemic agents. When
      considering along with its clinical outcome data and ease of application, the
      diagnostic accuracy of iFR supports its use as a suitable alternative to FFR for
      physiology-guided revascularization of moderate coronary stenoses. SUMMARY: We
      performed a meta-analysis of the diagnostic accuracy of iFR referenced to FFR.
      iFR showed excellent agreement with FFR as a resting index of coronary stenosis
      severity without the undesired effects and cost of hyperemic agents. This
      supports its use as a suitable alternative to FFR for physiology-guided
      revascularization of moderate coronary stenoses.

PMID- 29371085
TI  - (E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol attenuates PMA
      induced inflammatory responses in human monocytic cells through PKCdelta/JNK/AP-1
      pathways.
AB  - (E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a new (E)-2,4
      bis(p-hydroxyphenyl)-2 - butenal derivative, reportedly has therapeutic effects
      such as anti-arthritic properties. Although previous studies showed that MMPP has
      anti-arthritic effects on rheumatoid arthritis (RA), the anti-inflammation
      mechanism of MMPP remains unclear. In this study, phorbol-12-myristate 13-acetate
      (PMA) was used as an inflammatory stimulus to evaluate the detailed mechanism of
      the MMPP-mediated anti-inflammatory effect in human monocytic THP-1 cells. We
      investigated the effects of MMPP on inflammation-related pathways including
      protein kinase Cdelta (PKCdelta), mitogen-activated protein kinase, and activator
      protein-1 (AP-1). PMA induced the translocation of PKCs from the cytosol to the
      membrane and phosphorylated JNK. MMPP inhibited PMA-induced membrane
      translocation of PKCdelta, phosphorylation of JNK, and nuclear translocation of
      AP-1, resulting in downregulation of cyclooxygenase-2 and chemokine ligand 5
      production. These findings indicate that MMPP inhibits inflammatory responses in
      THP-1 cells by mitigating PMA-induced activation of PKCdelta and JNK and nuclear
      translocation of AP-1. Therefore, MMPP may be useful as an anti-inflammatory
      drug.

PMID- 29371086
TI  - Breast Cancer Screening in Women at Higher-Than-Average Risk: Recommendations
      From the ACR.
AB  - Early detection decreases breast cancer mortality. The ACR recommends annual
      mammographic screening beginning at age 40 for women of average risk. Higher-risk
      women should start mammographic screening earlier and may benefit from
      supplemental screening modalities. For women with genetics-based increased risk
      (and their untested first-degree relatives), with a calculated lifetime risk of
      20% or more or a history of chest or mantle radiation therapy at a young age,
      supplemental screening with contrast-enhanced breast MRI is recommended. Breast
      MRI is also recommended for women with personal histories of breast cancer and
      dense tissue, or those diagnosed by age 50. Others with histories of breast
      cancer and those with atypia at biopsy should consider additional surveillance
      with MRI, especially if other risk factors are present. Ultrasound can be
      considered for those who qualify for but cannot undergo MRI. All women,
      especially black women and those of Ashkenazi Jewish descent, should be evaluated
      for breast cancer risk no later than age 30, so that those at higher risk can be
      identified and can benefit from supplemental screening.

PMID- 29371087
TI  - Diagnostic Reference Levels for Adult Patients in the United States.

PMID- 29371088
TI  - Artificial Intelligence and Radiology: What Will the Future Hold?

PMID- 29371089
TI  - Can reversal of RYGB also reverse hypoglycemia?

PMID- 29371091
TI  - Risk Based Surveillance after Surgical Treatment of Renal Cell Carcinoma.
AB  - PURPOSE: We assessed the accuracy of the UISS (UCLA Integrated Staging System) to
      predict the postoperative recurrence of renal cell carcinoma. We also evaluated
      whether including patient age and tumor histology would improve clinical decision
      making. MATERIALS AND METHODS: We analyzed the records of 1,630 patients treated
      with nephrectomy at a single academic center. The accuracy of the UISS model to
      predict early (12 months or less) and late (more than 60 months) recurrence after
      surgery was compared with a new model including patient age and disease
      histology. RESULTS: The new model and the UISS model showed high accuracy to
      predict early recurrence after surgery (AUC 0.84, 95% CI 0.81-0.88 and 0.83, 95%
      CI 0.80-0.87, respectively). In patients diagnosed with low risk tumor types (eg
      papillary type 1 and chromophobe lesions) the average risk of early recurrence
      significantly decreased in each UISS risk category when tumor histology was added
      to the predictive model (low risk 1.6% vs 0.6%, intermediate risk 5.5% vs 1.9%
      and high risk 45% vs 22%). Kaplan-Meier analysis showed no difference in the risk
      of late recurrence among the UISS risk categories. CONCLUSIONS: The UISS model
      should be applied to tailor the early followup protocol after nephrectomy.
      Patients with low risk histology deserve less stringent followup regardless of
      the UISS risk category. Our results do not support a risk stratification model to
      design a surveillance protocol after 5 years postoperatively.

PMID- 29371090
TI  - Genome sequence and detection of peach rosette mosaic virus.
AB  - Peach rosette mosaic disease was first described in the 1940s affecting peach and
      plum. It was later determined that peach rosette mosaic virus (PRMV) is the
      causal agent of the disease. PRMV, a member of the genus Nepovirus, infects
      several perennial crops including stone fruit, grape and blueberry as well as
      several weed species found in orchards around the world. The molecular
      characterization of the virus is limited to partial genome sequences making it
      difficult to develop reliable and sensitive molecular detection tests; the reason
      that detection is routinely performed using ELISA with antibodies risen against a
      single virus isolate. Given the potential economic impact of the virus and the
      modes of transmission which, in addition to nematodes, include seed we studied
      PRMV in more depth using a modified dsRNA extraction protocol to obtain the virus
      genome. We determined the full nucleotide sequence and developed a protocol that
      detects conserved regions present in RNA 1 and RNA 2, making it an excellent
      alternative to the detection protocols used today.

PMID- 29371092
TI  - Hypertension in postmenopausal women: hemodynamic and therapeutic implications.

PMID- 29371093
TI  - In silico identification of potential epitopes present in human adenovirus
      proteins for vaccine design and of putative drugs for treatment against viral
      infection.
AB  - In silico approach using computational biology to design best probable epitopes
      and/or drug target(s) has given an edge to foresee active components for the
      treatment of many infectious diseases. This study aims to investigate the best
      probable epitopes from fiber, hexon and penton base proteins as well as probable
      drug targets to prevent and to cure adenovirus infection, respectively. After
      retrieving protein sequences, analysis of selection pressure; prediction of
      continuous/discontinuous B cell epitopes along with their antigenicity,
      immunogenicity, allergenicity; T cell epitopes along with their population
      coverage and echelon of conservancy were performed. Out of three proteins, fiber
      protein underwent the highest degree of selection pressure. Five peptides from
      fiber C-5, hexon C-5 and D-8, penton base B-3 and C-5 proteins were considered as
      the best potential B cell epitopes. Further analyses revealed that peptides
      present in fiber C-5, hexon C-5, penton base B-3 and C-5 proteins fulfilled the
      criteria of having surface accessibility, hydrophilicity, flexibility,
      antigenicity and beta turn. Several regions of proteins were identified as
      discontinuous B cell epitopes. Interestingly, a peptide present in 692-699 region
      of hexon C-5 and six amino acids at positions 100, 102, 105, 108, 112 and 114 of
      penton base B-3 proteins were recognized both as continuous and discontinuous B
      cell epitopes. Of all the predicted T cell epitopes, three nonamers from hexon C
      5, D-8 and penton base C-5 proteins may elicit strong immune response by
      activating both humoral and cellular immunity as these were found to overlap with
      those of B cell epitopic peptides. Considering non-allergen, conservancy and
      population coverage properties, "SGYDPYYTY" of hexon protein C-5 was further
      validated using in silico docking study for its interaction with the HLA allele.
      This study also demonstrated the possibility of compounds like 3-(azepan-1-ium-1
      yl) propane-1-sulfonate and E-5842 as the potential inhibitors of penton base and
      hexon proteins that could act as more effective drugs against the virus compared
      to the current ones. Therefore, further in vitro and animal model experiments
      using these predicted epitopes and compounds may pave the way for newer and more
      effective treatment approaches against adenovirus infection.

PMID- 29371095
TI  - Mean emotion from multiple facial expressions can be extracted with limited
      attention: Evidence from visual ERPs.
AB  - Human observers can readily extract the mean emotion from multiple faces shown
      briefly. However, it remains currently debated whether this ability depends on
      attention or not. To address this question, in this study, we recorded
      lateralized event-related brain potentials (i.e., N2pc and SPCN) to track covert
      shifts of spatial attention, while healthy adult participants discriminated the
      mean emotion of four faces shown in the periphery at an attended or unattended
      spatial location, using a cueing technique. As a control condition, they were
      asked to discriminate the emotional expression of a single face shown in the
      periphery. Analyses of saccade-free data showed that the mean emotion
      discrimination ability was above chance level but statistically undistinguishable
      between the attended and unattended location, suggesting that attention was not a
      pre-requisite for averaging. Interestingly, at the ERP level, covert shifts of
      spatial attention were captured by the N2pc and SPCN components. All together,
      these novel findings suggest that averaging multiple facial expressions shown in
      the periphery can operate with limited attention.

PMID- 29371094
TI  - Orthographic influence on spoken word identification: Behavioral and fMRI
      evidence.
AB  - The current study investigated behavioral and neuroimaging evidence for
      orthographic influences on auditory word identification. To assess such
      influences, the proportion of similar sounding words (i.e. phonological
      neighbors) that were also spelled similarly (i.e., orthographic neighbors) was
      computed for each auditorily presented word as the Orthographic-to-Phonological
      Overlap Ratio (OPOR). Speech intelligibility was manipulated by presenting
      monosyllabic words in multi-talker babble at two signal-to-noise ratios: + 3 and
      + 10 dB SNR. Identification rates were lower for high overlap words in the
      challenging + 3 dB SNR condition. In addition, BOLD contrast increased with OPOR
      at the more difficult SNR, and decreased with OPOR under more favorable SNR
      conditions. Both voxel-based and region of interest analyses demonstrated robust
      effects of OPOR in several cingulo-opercular regions. However, contrary to prior
      theoretical accounts, no task-related activity was observed in posterior regions
      associated with phonological or orthographic processing. We suggest that, when
      processing is difficult, orthographic-to-phonological feature overlap increases
      the availability of competing responses, which then requires additional support
      from domain general performance systems in order to produce a single response.

PMID- 29371096
TI  - First case of pleural empyema and pulmonary abscess caused by Eggerthia
      catenaformis.
AB  - Few data are available on the anaerobic bacterium Eggerthia catenaformis. Here we
      report the first clinical case of a patient with sepsis caused by pulmonary
      infection with E. catenaformis, and present the minimal inhibitory concentrations
      of different antimicrobial agents.

PMID- 29371097
TI  - Akt activation improves microregional oxygen supply/consumption balance after
      cerebral ischemia-reperfusion.
AB  - There have been reports that activation of Akt may provide neuroprotection after
      cerebral ischemia-reperfusion. We tested the hypothesis that activation of Akt
      would decrease infarct size and improve microregional O2 supply/consumption
      balance after cerebral ischemia-reperfusion. This hypothesis was tested in
      isoflurane-anesthetized rats with middle cerebral artery blockade for 1 h and
      reperfusion for 2 h with or without SC-79 (Akt activator, 0.05 mg/kg, three
      doses). Regional cerebral blood flow was determined using a C14-iodoantipyrine
      autoradiographic technique. Regional small vessel (20-60 MUm diameter) arterial
      and venous oxygen saturations were determined microspectrophotometrically. Akt
      phosphorylation was determined by Western blot. There were no significant
      hemodynamic or blood gas differences between groups. The control ischemic
      reperfused cortex had a similar O2 consumption, but lower blood flow and higher
      O2 extraction compared to the contralateral cortex. However, microregional O2
      supply/consumption balance was significantly reduced in the ischemic-reperfused
      cortex with many areas of low O2 saturation (42 of 80 veins with O2 saturation
      below 50%). SC-79 did not significantly affect cerebral O2 consumption, but
      significantly improved O2 supply/consumption balance in the reperfused area (18
      of 80 veins with O2 saturation below 50%). This was associated with a reduced
      cortical infarct size (13.3 +/- 0.5% control vs 6.7 +/- 0.3% SC-79). In control,
      Akt phosphorylation was elevated at 2 h after ischemia. With SC-79, Akt was
      activated at 15 min but not at 2 h in the ischemic reperfused area. These results
      suggest that early Akt activation is important for not only cell survival, but
      also for the control of local oxygen balance after cerebral ischemia-reperfusion.

PMID- 29371098
TI  - Distribution of Fos-immunoreactive neurons in the gustatory cortex elicited by
      intra-oral infusion of taste solutions in conscious rats.
AB  - The location of neurons in the gustatory cortex (GC) activated by intra-oral
      infusion of solutions in conscious rats was mapped using Fos
      immunohistochemistry. Groups of adult male Wistar rats (N's = 5) received an
      infusion of one of the following: dH2O, 0.1 or 1.0 M NaCl, 0.1 or 1.0 M sucrose,
      0.32 M MSG (with 100 uM amiloride and 2.5 M inosine 5'-monophosphate), 0.03 M
      HCl, or 0.003 M QHCl delivered via an intra-oral cannula (0.233 ml/min for 5
      min). Unstimulated control rats received no infusion. Taste reactivity (TR)
      behaviors were videotaped and scored. The number of Fos-immunoreactive (Fos-IR)
      neurons was counted in eight sections throughout the anterior-posterior extent of
      the GC in the medial and lateral halves of the granular (GI), dysgranular (DI),
      and dorsal (AID) and ventral (AIV) agranular insular cortices. Intra-oral
      infusion of dH2O, NaCl, or sucrose altered the number of Fos-IR neurons in only
      specific subareas of the GC and the effects of these tastants were concentration
      dependent. For example, 1.0 M NaCl increased Fos-IR neurons in the posterior
      lateral AID and DI and elicited more aversive TR responses than 0.1 M NaCl.
      Compared to dH2O, infusions of HCl or QHCl increased the total number of Fos-IR
      neurons in many subareas of the GC throughout its anterior-posterior extent and
      increased aversive TR behaviors. Linear regression analyses suggested that
      neurons in the medial AID of the posterior GC may influence aversive behavioral
      responses to HCl and QHCl while neurons in the posterior lateral AID and DI may
      play a role in aversive TR responses to 1.0 M NaCl.

PMID- 29371099
TI  - Pleiotropic and novel phenotypes in the Drosophila gut caused by mutation of drop
      dead.
AB  - Normal gut function is vital for animal survival, and deviations from such
      function can contribute to malnutrition, inflammation, increased susceptibility
      to pathogens, diabetes, neurodegenerative diseases, and cancer. In the fruit fly
      Drosophila melanogaster, mutation of the gene drop-dead (drd) results in
      defective gut function, as measured by enlargement of the crop and reduced food
      movement through the gut, and drd mutation also causes the unrelated phenotypes
      of neurodegeneration, early adult lethality and female sterility. In the current
      work, adult drd mutant flies are also shown to lack the peritrophic matrix (PM),
      an extracellular barrier that lines the lumen of the midgut and is found in many
      insects including flies, mosquitos and termites. The use of a drd-gal4 construct
      to drive a GFP reporter in late pupae and adults revealed drd expression in the
      anterior cardia, which is the site of PM synthesis in Drosophila. Moreover, the
      ability of drd knockdown or rescue with several gal4 drivers to recapitulate or
      rescue the gut phenotypes (lack of a PM, reduced defecation, and reduced adult
      survival 10-40 days post-eclosion) was correlated to the level of expression of
      each driver in the anterior cardia. Surprisingly, however, knocking down drd
      expression only in adult flies, which has previously been shown not to affect
      survival, eliminated the PM without reducing defecation rate. These results
      demonstrate that drd mutant flies have a novel phenotype, the absence of a PM,
      which is functionally separable from the previously described gut dysfunction
      observed in these flies. As the first mutant Drosophila strain reported to lack a
      PM, drd mutants will be a useful tool for studying the synthesis of this
      structure.

PMID- 29371100
TI  - The Zika Contraception Access Network: a feasibility programme to increase access
      to contraception in Puerto Rico during the 2016-17 Zika virus outbreak.
AB  - BACKGROUND: Prevention of unintended pregnancy is a primary strategy to reduce
      adverse pregnancy and birth outcomes related to Zika virus infection. The Zika
      Contraception Access Network (Z-CAN) aimed to build a network of health-care
      providers offering client-centred contraceptive counselling and the full range of
      reversible contraception at no cost to women in Puerto Rico who chose to prevent
      pregnancy during the 2016-17 Zika virus outbreak. Here, we describe the Z-CAN
      programme design, implementation activities, and baseline characteristics of the
      first 21 124 participants. METHODS: Z-CAN was developed by establishing
      partnerships between federal agencies, territorial health agencies, private
      corporations, and domestic philanthropic and non-profit organisations in the
      continental USA and Puerto Rico. Private donations to the National Foundation for
      the Centers for Disease Control and Prevention (CDCF) secured a supply of
      reversible contraceptive methods (including long-acting reversible
      contraception), made available to non-sterilised women of reproductive age at no
      cost through provider reimbursements and infrastructure supported by the CDCF. To
      build capacity in contraception service provision, doctors and clinic staff from
      all public health regions and nearly all municipalities in Puerto Rico were
      recruited into the programme. All providers completed 1 day of comprehensive
      training in contraception knowledge, counselling, and initiation and management,
      including the insertion and removal of long-acting reversible contraceptives
      (LARCs). Z-CAN was announced through health-care providers, word of mouth, and a
      health education campaign. Descriptive characteristics of programme providers and
      participants were recorded, and we estimated the factors associated with choosing
      and receiving a LARC method. As part of a Z-CAN programme monitoring plan,
      participants were invited to complete a patient satisfaction survey about whether
      they had obtained free, same-day access to their chosen contraceptive method
      after receiving comprehensive counselling, their perception of the quality of
      care they had received, and their satisfaction with their chosen method and
      services. FINDINGS: Between May 4, 2016, and Aug 15, 2017, 153 providers in the Z
      CAN programme provided services to 21 124 women. 20 110 (95%) women received same
      day provision of a reversible contraceptive method. Whereas only 767 (4%) women
      had used a LARC method before Z-CAN, 14 259 (68%) chose and received a LARC
      method at their initial visit. Of the women who received a LARC method, 10 808
      (76%) women had used no method or a least effective method of contraception (ie,
      condoms or withdrawal) before their Z-CAN visit. Of the 3489 women who
      participated in a patient satisfaction survey, 3068 (93%) of 3294 women were very
      satisfied with the services received, and 3216 (93%) of 3478 women reported
      receiving the method that they were most interested in after receiving
      counselling. 2382 (78%) of 3040 women rated their care as excellent or very good.
      INTERPRETATION: Z-CAN was designed as a short-term response for rapid
      implementation of reversible contraceptive services in a complex emergency
      setting in Puerto Rico and has served more than 21 000 women. This model could be
      replicated or adapted as part of future emergency preparedness and response
      efforts. FUNDING: National Foundation for the Centers for Disease Control and
      Prevention.

PMID- 29371101
TI  - Z-CAN: prevention of unintended pregnancy in an emergency setting.

PMID- 29371102
TI  - Methicillin-sensitive Staphylococcus aureus and emerging dominant sequence type
      188 Staphylococcus aureus in severe community-associated infections.

PMID- 29371103
TI  - Co-occurrence of mcr-1 in the chromosome and on an IncHI2 plasmid: persistence of
      colistin resistance in Escherichia coli.
AB  - Two colistin-resistant Escherichia coli strains (FS13Z2S and FS3Z6C) possessing
      chromosomally encoded mcr-1 isolated from swine were characterised. Whole-genome
      sequencing revealed that in strain FS13Z2S mcr-1 occurred in triplicate in the
      chromosome with another copy encoded on a pHNSHP45-2-like IncHI2 plasmid, whereas
      in strain FS3Z6C only one copy mcr-1 was inserted in the chromosome. It seems
      likely that the triplication of chromosomal copies of mcr-1 in FS13Z2S is due to
      intramolecular transposition events via a composite transposon containing an mcr
      1 cassette bracketed by two copies of insertion sequence ISApl1, and the pap2
      gene at the insertion site was truncated by an IS1294-like element. In plasmid
      pFS13Z2S and the chromosome of strain FS3Z6C, only a single copy of ISApl1 was
      present upstream of the mcr-1 cassette. The two strains exhibited similar
      colistin minimum inhibitory concentrations (MICs) and featured
      phosphoethanolamine addition to lipid A, without regard to the copy number of mcr
      1. The mcr-1-harbouring plasmid was unstable in wild-type strain FS13Z2S and was
      quickly lost after 7 days of passage on colistin-free Luria-Bertani broth
      containing 0.5% SDS, but the mcr-1 copies on the chromosome persisted. These
      results reveal that the single copy of mcr-1 could result in modification of
      lipopolysaccharide (LPS) and cause colistin resistance in E. coli. Acquisition of
      multiple copies of mcr-1, especially on the chromosome, would facilitate stable
      persistence of colistin resistance in the host strain.

PMID- 29371104
TI  - Activity of ceftazidime-avibactam against carbapenemase-producing
      Enterobacteriaceae from urine specimens obtained during the infection-carbapenem
      resistance evaluation surveillance trial (iCREST) in Spain.
AB  - The increasing rates of carbapenemase-producing Enterobacteriaceae (CPE)
      represent an important threat to health care systems and treatment of CPE
      infections is a challenge. The aim of the infection-carbapenem resistance
      evaluation surveillance trial (iCREST) was to determinate the prevalence of CPE
      in urine specimens in Spain and to evaluate the in vitro activity of ceftazidime
      avibactam. Urine specimens (n = 11 826) were included and activity of ceftazidime
      avibactam and comparators were investigated by broth microdilution in CPE.
      Carbapenemases were characterised by polymerase chain reaction (PCR) and
      sequencing as well as by whole genome sequencing (WGS). Overall prevalence of CPE
      was 1.6%. OXA-48 was the most prevalent (86.8%), followed by KPC (6.9%), VIM
      (4.8%), NDM (1.1%) and IMP (0.6%) carbapenemases. Klebsiella pneumoniae was the
      most common carbapenemase producer (87.8%). An uncommon carbapenemase type (IMP
      8) in Spain was identify by WGS in an Enterobacter cloacae isolate, reinforcing
      the utility of surveillance programmes as effectives tools to detect unexpected
      genes that encode antimicrobial resistance. Ceftazidime-avibactam showed 100%
      susceptibility in KPC and OXA-48 producers and the rates of susceptibility in CPE
      non-susceptible to ceftazidime or meropenem were 92.1% and 96.9%, respectively.
      Ceftazidime-avibactam could be considered an adequate treatment option for
      urinary tract infections caused by KPC and OXA-48 producers.

PMID- 29371105
TI  - Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase
      Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI
      mutations.
AB  - Until the introduction of dolutegravir (DTG), people living with HIV (PLWH) who
      have developed nucleoside reverse transcriptase inhibitor (NRTI) mutations have
      had few other treatment options outside of regimens based on ritonavir-boosted
      protease inhibitors (PI/r). Here we report treatment results among PLWH in Sweden
      with pre-existing NRTI mutations on antiretroviral treatment (ART) with DTG and
      one to two NRTIs. All PLWH on ART with DTG and one to two NRTIs with pre-existing
      NRTI mutations were retrospectively identified from the National InfCare HIV
      database. As controls, PLWH on PI/r and one to two NRTIs, matched according to
      Genotypic Susceptibility Score and observation time, were included. Data were
      collected as long as the study population was on treatment with DTG; controls
      were monitored for the same interval. Outcome was classified as either treatment
      success or failure. In total, 244 participants (122 individuals treated with DTG
      and 122 individuals treated with PI/r) were included. Median observation time was
      78 weeks (interquartile range 50-98 weeks) for participants on DTG and 75 weeks
      (50-101 weeks) for individuals on PI/r. Viral failure was detected in four
      individuals treated with DTG and three individuals treated with PI/r, resulting
      in similar success rates of 96.7% and 97.5%, respectively. No new mutations were
      found among participants with treatment failure. DTG in combination with one to
      two NRTIs was as efficient as PI/r in individuals with pre-existing NRTI
      mutations in this setting. It may be considered an alternative to PI/r-based ART
      even in the presence of NRTI resistance.

PMID- 29371107
TI  - Advance Directive Utilization Is Associated with Less Aggressive End-of-Life Care
      in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is associated with
      significant morbidity and mortality, making advance care planning (ACP) and
      management especially important in this patient population. A paucity of data
      exists on the utilization of ACP among allogeneic HCT recipients and the
      relationship between ACP and intensity of healthcare utilization in these
      patients. We performed a retrospective review of patients receiving allogeneic
      HCT at our institution from 2008 to 2015 who had subsequently died after HCT.
      Documentation and timing of advance directive (AD) completion were abstracted
      from the electronic medical record. Outcomes of interest included use of
      intensive care unit (ICU) level of care at any time point after HCT, within 30
      days of death, and within 14 days of death; use of mechanical ventilation at any
      time after HCT; and location of death. Univariate logistic regression was
      performed to explore associations between AD completion and each outcome. Of the
      1031 patients who received allogeneic HCT during the study period, 422 decedents
      (41%) were included in the analysis. Forty-four percent had AD documentation
      prior to death. Most patients (69%) indicated that if terminally ill, they did
      not wish to be subjected to life-prolonging treatment attempts. Race/ethnicity
      was significantly associated with AD documentation, with non-Hispanic white
      patients documenting ADs more frequently (51%) compared with Hispanic (22%) or
      Asian patients (35%; P = .0007). Patients with ADs were less likely to use the
      ICU during the transplant course (41% for patients with ADs versus 52% of
      patients without ADs; P = .03) and also were less likely to receive mechanical
      ventilation at any point after transplantation (21% versus 37%, P < .001). AD
      documentation was also associated with decreased ICU use at the end of life;
      relative to patients without ADs, patients with ADs were more likely to die at
      home or in hospital as opposed to in the ICU (odds ratio, .44; 95% confidence
      interval, .27 to .72). ACP remains underused in allogeneic HCT. Adoption of a
      systematic practice to standardize AD documentation as part of allogeneic HCT
      planning has the potential to significantly reduce ICU use and mechanical
      ventilation while improving quality of care at end of life in HCT recipients.

PMID- 29371106
TI  - Cardiorespiratory demand and rate of perceived exertion during overground walking
      with a robotic exoskeleton in long-term manual wheelchair users with chronic
      spinal cord injury: A cross-sectional study.
AB  - BACKGROUND: Many wheelchair users adopt a sedentary lifestyle, which results in
      progressive physical deconditioning with increased risk of musculoskeletal,
      cardiovascular and endocrine/metabolic morbidity and mortality. Engaging in a
      walking program with an overground robotic exoskeleton may be an effective
      strategy for mitigating these potential negative health consequences and
      optimizing fitness in this population. However, additional research is warranted
      to inform the development of adapted physical activity programs incorporating
      this technology. OBJECTIVES: To determine cardiorespiratory demands during
      sitting, standing and overground walking with a robotic exoskeleton and to verify
      whether such overground walking results in at least moderate-intensity physical
      exercise. METHODS: We enrolled 13 long-term wheelchair users with complete motor
      spinal cord injury in a walking program with an overground robotic exoskeleton.
      Cardiorespiratory measures and rate of perceived exertion (RPE) were recorded by
      using a portable gas analyzer system during sitting, standing and four 10m
      walking tasks with the robotic exoskeleton. Each participant also performed an
      arm crank ergometer test to determine maximal cardiorespiratory ability (i.e.,
      peak heart rate and O2 uptake [HRpeak, VO2peak]). RESULTS: Cardiorespiratory
      measures increased by a range of 9%-35% from sitting to standing and further
      increased by 22%-52% from standing to walking with the robotic exoskeleton.
      During walking, median oxygen cost (O2Walking), relative HR (%HRpeak), relative
      O2 consumption (%VO2peak) and respiratory exchange ratio (RER) reached
      0.29mL/kg/m, 82.9%, 41.8% and 0.9, respectively, whereas median RPE reached
      3.2/10. O2Walking was moderately influenced by total number of sessions and steps
      taken with the robotic exoskeleton since the start of the walking program.
      CONCLUSION: Overground walking with the robotic exoskeleton over a short distance
      allowed wheelchair users to achieve a moderate-intensity level of exercise.
      Hence, an overground locomotor training program with a robotic exoskeleton may
      have cardiorespiratory health benefits in the population studied.

PMID- 29371108
TI  - The importance of area scaling with FACS DIVA software.
AB  - With the release and use of the Becton Dickenson FACS Diva Software, the use of
      Area as the default parameter came into play. As such, the use of area as a
      calculated parameter, methods were needed to be employed to ensure doublet
      discrimination and proper display on standard FSC/SSC. Improper setting of
      forward area scaling can alter the display cell populations. This combined with
      improper area gating strategy can lead to doublet inclusion which in sorting rare
      events can compromise sort purity. In extreme cases where area scaling with the
      individual lasers is ignored, differences can exist between Area and Height where
      compensation will likely not be optimal, particularly if one parameter - usually
      height is saturated. In addition, area scaling can impact population grouping. As
      FSC and individual laser area scaling is a function of event size, the most
      common error is to accept the setting determined by CS&T, which are 3.2 um
      particles and proceed with the sample(s) without regard to the sample's actual
      size. With cellular events smaller or more likely larger than the CS&T beads,
      this will make the area scaling settings less than optimal. Analysis and sorting
      rare events with populations larger than the CS&T beads can be compromised if
      adjustments in FSC area scaling are not addressed. Proper FSC and laser area
      scaling must be determined empirically for each sample. Examples of the effects
      of sample size on area scaling will be presented in addition to gating and
      templates for determining area scaling.

PMID- 29371109
TI  - Functional genetic variants within the SIRT2 gene promoter in type 2 diabetes
      mellitus.
AB  - AIMS: Type 2 diabetes mellitus (T2D) is a common and complex metabolic diseases
      caused by interactions between environmental and genetic factors. Genome-wide
      association studies have identified more than 80 common genetic variants for T2D,
      which account for only ~10% of the heritability of T2D cases. SIRT2, a member of
      NAD(+)-dependent class III deacetylases, is involved in genomic stability,
      metabolism, inflammation, oxidative stress and autophagy. In maintaining
      metabolic homeostasis, SIRT2 regulates adipocyte differentiation, fatty acid
      oxidation, gluconeogenesis, and insulin sensitivity. Thus, we hypothesized that
      DNA sequence variants (DSVs) in SIRT2 gene promoter may change SIRT2 levels,
      contributing to T2D. METHODS: SIRT2 gene promoter was genetically and
      functionally analyzed in large cohorts of T2D patients (n = 365) and ethnic
      matched controls (n = 358). RESULTS: A total of 18 DSVs, including 5 SNPs, were
      identified in this study. Four novel heterozygous DSVs (g.38900912G > T,
      g.38900561C > T, g.38900359C > T and g.38900237G > A) were identified in four T2D
      patients, three of which (g.38900912G > T, g.38900359C > T and g.38900237G > A)
      significantly increased the transcriptional activity of the SIRT2 gene promoter
      in cultured pancreatic beta cells (P < .01). Seven novel heterozygous DSVs were
      only found in controls, and one heterozygous deletion DSV and five SNPs were
      found in both T2D patients and controls, which did not significantly affect SIRT2
      gene promoter activity (P > .05). CONCLUSIONS: Our findings suggested that the
      DSVs may increase SIRT2 gene promoter activity and SIRT2 levels, contributing to
      T2D development as a risk factor.

PMID- 29371110
TI  - Intramembranal disulfide cross-linking elucidates the super-quaternary structure
      of mammalian CatSpers.
AB  - CatSper is a voltage-dependent calcium channel located in the plasma membrane of
      the sperm flagellum and is responsible for triggering hyperactive motility. A
      homology model for the transmembrane region was built in which the arrangement of
      the subunits around the pseudo-four-fold symmetry axis was deduced by the pairing
      of conserved transmembranal cysteines across mammals. Directly emergent of the
      predicted quaternary structure is an architecture in which tetramers polymerize
      through additional, highly conserved cysteines, creating one or more double-rows
      channels extending the length of the principal piece of the mammalian sperm tail.
      The few species that are missing these cysteines are eusocial or otherwise
      monogamous, suggesting that sperm competition is selective for a disulfide
      crosslinked macromolecular architecture. The model suggests testable hypotheses
      for how CatSper channel opening might behave in response to pH, 2
      arachidonoylglycerol, and mechanical force. A flippase function is hypothesized,
      and a source of the concomitant disulfide isomerase activity is found in CatSper
      associated proteins beta, delta and epsilon.

PMID- 29371111
TI  - Globular chitosan prolongs the effective duration time and decreases the acute
      toxicity of botulinum neurotoxin after intramuscular injection in rats.
AB  - Botulinum neurotoxin (BoNT) is used for an increasing number of neurological and
      non-neurological indications and disorders. Since the duration of action of this
      neurotoxin is limited, the goal of the work was to improve the pharmacological
      time course of BoNT. We explored the effect of several polysaccharides on the
      duration of action of BoNT/A1 in rat electromyography. The formulation of BoNT/A1
      containing globular chitosan increased the threshold stimulation intensity almost
      2 times in 30 days after injection if compared with the baseline threshold.
      However, conventional linear chitosan, heparin and hyaluronic acid did not have
      such an effect. In addition, we compared the effectiveness of different doses of
      BoNT/A1 (25, 50, 75, and 100 U) with globular chitosan and compared the acute
      toxicity of this formulation with that of BoNT/A1 in physiological saline after
      intramuscular injection. The results demonstrated that the dose 25 U of BoNT/A1
      with globular chitosan was both effective and safe for animals after
      intramuscular injection. The assessed median lethal dose (LD50) for intramuscular
      injection in rats was 1.4 times higher for a combination of BoNT/A1 with globular
      chitosan than that for a solution of BoNT/A1 in physiological saline. Thus, the
      results of our study have provided evidence that intramuscular injection of the
      formulation of BoNT/A1 (25 U) containing globular chitosan in rats is safe and
      significantly prolongs the effective duration time of BoNT/A1.

PMID- 29371112
TI  - Manipulation and mobilization for treating chronic low back pain: a systematic
      review and meta-analysis.
AB  - BACKGROUND CONTEXT: Mobilization and manipulation therapies are widely used to
      benefit patients with chronic low back pain. However, questions remain about
      their efficacy, dosing, safety, and how these approaches compare with other
      therapies. PURPOSE: The present study aims to determine the efficacy,
      effectiveness, and safety of various mobilization and manipulation therapies for
      treatment of chronic low back pain. STUDY DESIGN/SETTING: This is a systematic
      literature review and meta-analysis. OUTCOME MEASURES: The present study measures
      self-reported pain, function, health-related quality of life, and adverse events.
      METHODS: We identified studies by searching multiple electronic databases from
      January 2000 to March 2017, examining reference lists, and communicating with
      experts. We selected randomized controlled trials comparing manipulation or
      mobilization therapies with sham, no treatment, other active therapies, and
      multimodal therapeutic approaches. We assessed risk of bias using Scottish
      Intercollegiate Guidelines Network criteria. Where possible, we pooled data using
      random-effects meta-analysis. Grading of Recommendations, Assessment,
      Development, and Evaluation (GRADE) was applied to determine the confidence in
      effect estimates. This project is funded by the National Center for Complementary
      and Integrative Health under Award Number U19AT007912. RESULTS: Fifty-one trials
      were included in the systematic review. Nine trials (1,176 patients) provided
      sufficient data and were judged similar enough to be pooled for meta-analysis.
      The standardized mean difference for a reduction of pain was SMD=-0.28, 95%
      confidence interval (CI) -0.47 to -0.09, p=.004; I2=57% after treatment; within
      seven trials (923 patients), the reduction in disability was SMD=-0.33, 95% CI 
      0.63 to -0.03, p=.03; I2=78% for manipulation or mobilization compared with other
      active therapies. Subgroup analyses showed that manipulation significantly
      reduced pain and disability, compared with other active comparators including
      exercise and physical therapy (SMD=-0.43, 95% CI -0.86 to 0.00; p=.05, I2=79%;
      SMD=-0.86, 95% CI -1.27 to -0.45; p<.0001, I2=46%). Mobilization interventions,
      compared with other active comparators including exercise regimens, significantly
      reduced pain (SMD=-0.20, 95% CI -0.35 to -0.04; p=.01; I2=0%) but not disability
      (SMD=-0.10, 95% CI -0.28 to 0.07; p=.25; I2=21%). Studies comparing manipulation
      or mobilization with sham or no treatment were too few or too heterogeneous to
      allow for pooling as were studies examining relationships between dose and
      outcomes. Few studies assessed health-related quality of life. Twenty-six of 51
      trials were multimodal studies and narratively described. CONCLUSION: There is
      moderate-quality evidence that manipulation and mobilization are likely to reduce
      pain and improve function for patients with chronic low back pain; manipulation
      appears to produce a larger effect than mobilization. Both therapies appear safe.
      Multimodal programs may be a promising option.

PMID- 29371114
TI  - A Kappa Opioid Receptor Agonist Blocks Bone Cancer Pain Without Altering Bone
      Loss, Tumor Size, or Cancer Cell Proliferation in a Mouse Model of Cancer-Induced
      Bone Pain.
AB  - : Breast cancer metastasizes to bone, diminishing quality of life of patients
      because of pain, fracture, and limited mobility. Cancer-induced bone pain (CIBP)
      is characterized as moderate to severe ongoing pain, primarily managed by mu
      opioid agonists such as fentanyl. However, opioids are limited by escalating
      doses and serious side effects. One alternative may be kappa opioid receptor
      (KOR) agonists. There are few studies examining KOR efficacy on CIBP, whereas KOR
      agonists are efficacious in peripheral and inflammatory pain. We thus examined
      the effects of the KOR agonist U50,488 given twice daily across 7 days to block
      CIBP, tumor-induced bone loss, and tumor burden. U50,488 dose-dependently blocked
      tumor-induced spontaneous flinching and impaired limb use, without changing
      tactile hypersensitivity, and was fully reversed by the KOR antagonist nor
      binaltorphimine. U50,488 treatment was higher in efficacy and duration of action
      at later time points. U50,488 blocked this pain without altering tumor-induced
      bone loss or tumor growth. Follow-up studies in human cancer cell lines confirmed
      that KOR agonists do not affect cancer cell proliferation. These studies suggest
      that KOR agonists could be a new target for cancer pain management that does not
      induce cancer cell proliferation or alter bone loss. PERSPECTIVE: This study
      demonstrates the efficacy of KOR agonists in the treatment of bone cancer-induced
      pain in mice, without changing tumor size or proliferation in cancer cell lines.
      This suggests that KOR agonists could be used to manage cancer pain without the
      drawbacks of mu opioid agonists and without worsening disease progression.

PMID- 29371115
TI  - Time to awakening after cardiac arrest and the association with target
      temperature management.
AB  - AIM: Target temperature management (TTM) at 32-36  degrees C is recommended in
      unconscious survivors of cardiac arrest. This study reports awakening in the TTM
      trial. Our predefined hypotheses were that time until awakening correlates with
      long-term neurological outcome and is not affected by level of TTM. METHODS: Post
      hoc analysis of time until awakening after cardiac arrest, its association with
      long-term (180-days) neurological outcome and predictors of late awakening (day 5
      or later). The trial randomized 939 comatose survivors to TTM at 33  degrees C or
      36  degrees C with strict criteria for withdrawal of life-sustaining therapies.
      Administered sedation in the treatment groups was compared. Awakening was defined
      as a Glasgow Coma Scale motor score 6. RESULTS: 496 patients had registered day
      of awakening in the ICU, another 43 awoke after ICU discharge. Good neurological
      outcome was more common in early (275/308, 89%) vs late awakening (142/188, 76%),
      p < 0.001. Awakening occurred later in TTM33 than in TTM36 (p = 0.002) with no
      difference in neurological outcome, or cumulative doses of sedative drugs at 12,
      24 or 48 h. TTM33 (p = 0.006), clinical seizures (p = 0.004), and lower GCS-M on
      admission (p = 0.03) were independent predictors of late awakening. CONCLUSION:
      Late awakening is common and often has a good neurological outcome. Time to
      awakening was longer in TTM33 than in TTM36, this difference could not be
      attributed to differences in sedative drugs administered during the first 48 h.

PMID- 29371116
TI  - Cardiac arrest and breathing, why bother?

PMID- 29371113
TI  - Ecological Momentary Assessment Methodology in Chronic Pain Research: A
      Systematic Review.
AB  - : Self-reported pain intensity assessments are central to chronic pain research.
      Ecological momentary assessment (EMA) methodologies are uniquely positioned to
      collect these data, and are indeed being used in the field. However, EMA
      protocols are complex, and many decisions are necessary in the design of EMA
      research studies. A systematic literature review identified 105 articles drawing
      from 62 quantitative EMA research projects examining pain intensity in adult
      chronic pain patients. Study characteristics were tabulated to summarize and
      describe the use of EMA, with an emphasis placed on various dimensions of
      decision-making involved in executing EMA methodologies. Most identified studies
      considered within-person relationships between pain and other variables, and a
      few examined interventions on chronic pain. There was a trend toward the use of
      smartphones as EMA data collection devices more recently, and completion rates
      were not reported in nearly one third of studies. Pain intensity items varied
      widely with respect to number of scale points, anchor labels, and length of
      reporting period; most used numeric rating scales. Recommendations are provided
      for reporting to improve reproducibility, comparability, and interpretation of
      results, and for opportunities to clarify the importance of design decisions.
      PERSPECTIVE: Studies that use EMA methodologies to assess pain intensity are
      heterogeneous. Aspects of protocol design, including data input modality and pain
      item construction, have the potential to influence the data collected. Thorough
      reporting on design features and completion rates therefore facilitates
      reproducibility, comparability, and interpretation of study results.

PMID- 29371117
TI  - Activation of free sperm and dissociation of sperm bundles (spermatozeugmata) of
      an endangered viviparous fish, Xenotoca eiseni.
AB  - Knowledge of sperm motility activation for viviparous fishes has been limited to
      study of several species in Poeciliidae, and the dissociation of sperm bundles is
      even less understood. The goal of this study was to use the endangered Redtail
      Splitfin (Xenotoca eiseni) as a model to investigate the activation of sperm from
      viviparous fishes by study of free sperm and spermatozeugmata (unencapsulated
      sperm bundles). The specific objectives were to evaluate the effects of: (1)
      osmotic pressure and refrigerated storage (4  degrees C) on activation of free
      sperm, (2) osmotic pressure, ions, and pH on dissociation of spermatozeugmata,
      and (3) CaCl2 concentration and pH on sperm membrane integrity. Free sperm were
      activated in Ca2+-free Hanks' balanced salt solution at 81-516 mOsmol/kg. The
      highest motility (19 +/- 6%) was at 305 mOsmol/kg and swim remained for 84 h.
      Glucose (300-700 mOsmol/kg), NaCl (50-600 mOsmol/kg), and KCl, MgCl2, and MnCl2
      at 5-160 mM activated sperm within spermatozeugmata, but did not dissociate
      spermatozeugmata. CaCl2 at 5-160 mM dissociated spermatozeugmata within 10 min.
      Solutions of NaCl-NaOH at pH 11.6 to 12.4 dissociated spermatozeugmata within 1
      min. The percentage of viable cells had no significant differences (P = 0.2033)
      among different concentrations of CaCl2, but it was lower (P < 0.0001) at pH 12.5
      than at pH between 7.0 and 12.0. Overall, this study provided a foundation for
      quality evaluation of sperm and spermatozeugmata from livebearing fishes, and for
      development of germplasm repositories for imperiled goodeids.

PMID- 29371119
TI  - How to Perform a Systematic Review and Meta-analysis of Diagnostic Imaging
      Studies.
AB  - A systematic review is a comprehensive search, critical evaluation, and synthesis
      of all the relevant studies on a specific (clinical) topic that can be applied to
      the evaluation of diagnostic and screening imaging studies. It can be a
      qualitative or a quantitative (meta-analysis) review of available literature. A
      meta-analysis uses statistical methods to combine and summarize the results of
      several studies. In this review, a 12-step approach to performing a systematic
      review (and meta-analysis) is outlined under the four domains: (1) Problem
      Formulation and Data Acquisition, (2) Quality Appraisal of Eligible Studies, (3)
      Statistical Analysis of Quantitative Data, and (4) Clinical Interpretation of the
      Evidence. This review is specifically geared toward the performance of a
      systematic review and meta-analysis of diagnostic test accuracy (imaging)
      studies.

PMID- 29371118
TI  - Ankyrin repeat domain 1 regulates innate immune responses against herpes simplex
      virus 1: A potential role in eczema herpeticum.
AB  - BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease. A
      subset of patients with AD are susceptible to disseminated herpes simplex virus
      (HSV) infection, a complication termed eczema herpeticum (ADEH+). The immune
      mechanisms causing ADEH+ remain elusive. Using RNA sequencing, we recently found
      that ankyrin repeat domain 1 (ANKRD1) was significantly induced in human PBMCs
      upon HSV-1 stimulation, and its induction in patients with ADEH+ was
      significantly reduced compared with that seen in AD patients without a history of
      eczema herpeticum (ADEH-). OBJECTIVE: We sought to validate ANKRD1 gene
      expression in nonatopic (NA) subjects, patients with ADEH-, and patients with
      ADEH+ and to delineate the biological function of ANKRD1 and the signaling
      pathway or pathways involved. METHODS: Purification of human PBMCs, monocytes, B
      cells, dendritic cells, T cells, and natural killer cells; RNA extraction and
      quantitative RT-PCR; small interfering RNA technique; co-immunoprecipitation; and
      Western blot assays were used. RESULTS: ANKRD1 expression was significantly
      reduced in PBMCs from patients with ADEH+ after HSV-1 stimulation compared with
      PBMCs from patients with ADEH-. We found that the induction of ANKRD1 by HSV-1
      and multiple pattern recognition receptor agonists are mediated by inflammatory
      cytokines. Silencing ANKRD1 gene expression in antigen-presenting cells led to
      increased viral load and reduced IFNB1 and IL29 production. Using co
      immunoprecipitation methods, we demonstrated that ANKRD1 formed protein complexes
      with interferon regulatory factor (IRF) 3 and IRF7, which are important
      transcription factors regulating signaling transduction of pattern recognition
      receptors. Overexpression of ANKRD1 enhanced the IRF3-mediated signaling
      pathways. CONCLUSION: ANKRD1 is involved in IRF3-mediated antiviral innate immune
      signaling pathways. Its reduced expression in patients with ADEH+ might
      contribute to the pathogenesis of ADEH+.

PMID- 29371120
TI  - Coregistration of Preoperative MRI with Ex Vivo Mesorectal Pathology Specimens to
      Spatially Map Post-treatment Changes in Rectal Cancer Onto In Vivo Imaging:
      Preliminary Findings.
AB  - RATIONALE AND OBJECTIVES: The objective of this study was to develop and
      quantitatively evaluate a radiology-pathology fusion method for spatially mapping
      tissue regions corresponding to different chemoradiation therapy-related effects
      from surgically excised whole-mount rectal cancer histopathology onto
      preoperative magnetic resonance imaging (MRI). MATERIALS AND METHODS: This study
      included six subjects with rectal cancer treated with chemoradiation therapy who
      were then imaged with a 3-T T2-weighted MRI sequence, before undergoing
      mesorectal excision surgery. Excised rectal specimens were sectioned, stained,
      and digitized as two-dimensional (2D) whole-mount slides. Annotations of residual
      disease, ulceration, fibrosis, muscularis propria, mucosa, fat, inflammation, and
      pools of mucin were made by an expert pathologist on digitized slide images. An
      expert radiologist and pathologist jointly established corresponding 2D sections
      between MRI and pathology images, as well as identified a total of 10
      corresponding landmarks per case (based on visually similar structures) on both
      modalities (five for driving registration and five for evaluating alignment). We
      spatially fused the in vivo MRI and ex vivo pathology images using landmark-based
      registration. This allowed us to spatially map detailed annotations from 2D
      pathology slides onto corresponding 2D MRI sections. RESULTS: Quantitative
      assessment of coregistered pathology and MRI sections revealed excellent
      structural alignment, with an overall deviation of 1.50 +/- 0.63 mm across five
      expert-selected anatomic landmarks (in-plane misalignment of two to three pixels
      at 0.67- to 1.00-mm spatial resolution). Moreover, the T2-weighted intensity
      distributions were distinctly different when comparing fibrotic tissue to
      perirectal fat (as expected), but showed a marked overlap when comparing fibrotic
      tissue and residual rectal cancer. CONCLUSIONS: Our fusion methodology enabled
      successful and accurate localization of post-treatment effects on in vivo MRI.

PMID- 29371121
TI  - Virtual Computed Tomography Colonography: Evaluation of 2D and Virtual 3D Image
      Quality of Sub-mSv Examinations Enabled by Third-generation Dual Source Scanner
      Featuring Tin Filtering.
AB  - RATIONALE AND OBJECTIVES: To evaluate two- and three-dimensional (2D and 3D)
      image quality of sub-milliSievert (mSv) computed tomography (CT) colonography
      utilizing a third-generation dual source CT scanner featuring a tin filter.
      METHODS: We retrospectively evaluated 26 consecutive patients who underwent third
      generation dual source CT colonography, nine with the standard-dose clinical-scan
      protocol (SDP) and 17 with a low-dose protocol (LDP) featuring a tin filter.
      Radiation dose was evaluated by volume computed tomography dose index (CTDIvol),
      dose length product (DLP), effective dose (E), and size-specific dose estimate.
      Objective image quality was evaluated utilizing signal-to-noise ratio (SNR)
      derived from standardized placed regions of interest on the transverse 2D images
      and the ratio of SNR/CTDIvol (normalized SNR). Two radiologists in consensus
      assessed subjective image quality of the virtual 3D images. RESULTS: There were
      no significant differences in subjective image quality (P = .661). All
      examinations were rated "excellent" or "good" for diagnostic confidence. The mean
      total for DLP/E was 143.4 +/- 29.8 mGy/3.00 +/- 0.40 mSv in the SDP and therefore
      significantly higher than in the LDP with 36.9 +/- 8.7 mGy/0.75 +/- 0.16 mSv (P <
      .001). The SNR was 8.9 +/- 2.1 in the SDP and 4.9 +/- 0.8 in the LDP.
      CONCLUSIONS: Third-generation dual source CT featuring a tin filter enables
      consistent sub-mSv colonography without substantially impairing image quality.

PMID- 29371122
TI  - Diagnostic Value of Dual-input Computed Tomography Perfusion on Detecting
      Bronchial-Pulmonary Artery Fistula in Tuberculosis Patients with Massive
      Hemoptysis.
AB  - RATIONALE AND OBJECTIVES: This prospective study aimed to evaluate the diagnostic
      performance of dual-input computed tomography perfusion technique (DI-CTP) in
      identifying the bronchial-pulmonary artery fistula in patients tuberculosis with
      massive hemoptysis. MATERIAL AND METHODS: Twenty patients with tuberculosis with
      massive hemoptysis were enrolled from January 2015 to December 2015. The
      association between DI-CTP parameters and the diagnostic outcomes of digital
      subtraction angiography was assessed. Diagnostic efficacy of DI-CTP was evaluated
      by receiver operating curve (ROC) analyses using the diagnostic outcomes of
      digital subtraction angiography, which is the gold standard for identifying
      bronchial-pulmonary artery fistula. RESULTS: Compared to lung segments with
      normal blood flow (n = 304), those with bronchial-pulmonary artery fistula (n =
      164) had a reduced pulmonary flow value, perfusion index (PI) value, and an
      elevated bronchial artery (BF) value in the DI-CTP scan, which was further
      confirmed by multivariate logistic regression. ROC analysis showed that PI and
      bronchial artery has an excellent diagnostic performance (both area under the ROC
      curve > 0.9, P < .001) and high sensitivity and specificity (from 0.79 to 0.95 at
      the optimal cutoff). PI has the best diagnostic performance, with an overall
      diagnostic accuracy of 0.91. CONCLUSIONS: DI-CTP scan possesses the diagnostic
      value for detecting bronchial-pulmonary artery fistula in patients with
      tuberculosis with massive hemoptysis, providing an alternative diagnostic method.

PMID- 29371123
TI  - Methodologies for assessing the acceptability of oral formulations among children
      and older adults: a systematic review.
AB  - Acceptability of medicinal products in children and older populations is pivotal
      in ensuring adherence and therapeutic outcomes. This review systematically
      identifies studies reporting on formulation aspects of oral medications that
      affect their acceptability in these patient groups. Particular emphasis is placed
      on the evaluation of the methodologies employed in the studies. Sixty-eight
      studies were included for analysis, with 51 (75%) in children and 17 (25%) in
      older populations. The studies evaluated a range of oral formulations; however,
      the methodologies used differ considerably in participants' characteristics,
      study settings, tools, acceptability definitions and criteria. It is evident that
      there is a lack of standardisation in study design as well as the assessment
      methods used in assessing acceptability of medicines in children and older
      populations.

PMID- 29371124
TI  - Proteomic profiling of the midgut contents of Haemaphysalis flava.
AB  - Scant information is available regarding the proteins involved in blood meal
      processing in ticks. Here, we aimed to highlight the midgut proteins involved in
      preventing blood meal coagulation, and in facilitating intracellular digestion in
      the tick Haemaphysalis flava. Proteins were extracted from the midgut contents of
      fully engorged and partially engorged ticks. We used liquid chromatography tandem
      mass spectrometry (LC-MS/MS) analysis to identify 131 unique peptides, and 102
      proteins. Of these, 15 proteins, each with at least two unique peptides, were
      recognized with high confidence. We also retrieved 18 unigenes from our previous
      published transcriptomic libraries of the midguts and salivary glands of H.
      flava, and inferred the primary structures of nine proteins and fragments of five
      proteins. There were 23 and 21 unique proteins in the midgut contents of fully
      engorged and partially engorged ticks, respectively. We detected 58 shared
      proteins in the midgut contents of both fully engorged and partially engorged
      ticks. Of these, seven were significantly differentially expressed between fully
      engorged and partially engorged ticks: actin, calmodulin, elongation factor
      1alpha, hsp90, multifunctional chaperone, tubulin alpha, and tubulin beta. Our
      results demonstrated that the proteome of the midgut contents, combined with the
      transcriptome of the midgut, was a viable method for the reinforcement of protein
      identification. This method will facilitate further study of blood meal
      processing by ticks, as well as the identification of clues for tick infestation
      control. The existence of numerous proteins detected in the midgut contents also
      highlight the complexity of blood digestion in ticks; this area is in need of
      further investigation.

PMID- 29371125
TI  - Confirming Rickettsia rickettsii as the etiological agent of lethal spotted fever
      group rickettsiosis in human patients from Espirito Santo state, Brazil.
AB  - Although Espirito Santo state is considered an endemic area for Brazilian spotted
      fever (BSF) with related lethal cases, it also constitutes the only state of
      southeastern Brazil that currently lacks a specific confirmation of the specific
      rickettsial agent. In an attempt to a species level confirmation of the
      etiological agent of fatal rickettsiosis cases in Espirito Santo state, in this
      study we tested human sera obtained between 2015 to 2017 by means of qPCR and
      subsequent conventional PCR protocols targeting gltA (citrate synthase) and ompA
      (190-kDA outer membrane protein) rickettsial genes. All samples were found to
      contain rickettsial DNA through the citrate synthase qPCR protocol. By
      conventional PCR, rickettsial gltA and ompA specific DNA fragments were detected
      in 25% (one sample) and 50% (2 samples) of the screened sera, respectively.
      Obtained consensuses for each gene partial sequences were 100% identical to
      Rickettsia rickettsii gltA and ompA genes. The present study confirms for the
      first time R. rickettsii as the etiological agent of a lethal spotted fever group
      rickettsiosis in human patients from Espirito Santo state.

PMID- 29371128
TI  - Muscle Strength and Functional Limitations: Preserving Function in Older Mexican
      Americans.
AB  - OBJECTIVES: Understanding the role of muscle strength as a preventive factor for
      shorter-term declines in function may provide further insights into the disabling
      process. This study examined if muscle strength was associated with 2-year
      preservation of instrumental activities of daily living (IADL) function and
      activities of daily living (ADL) disability status in older Mexican Americans.
      DESIGN: Longitudinal, panel. SETTING: Urban and rural households in the
      Southwestern United States. PARTICIPANTS: A subsample of 672 Mexican Americans
      aged at least 65 years was followed for 2 years. MEASUREMENTS: Muscle strength
      was assessed with a hand-held dynamometer. IADL and ADL were self-reported.
      Covariate-adjusted ordinal and multinomial logistic models were used to determine
      the association between handgrip strength and changes in IADL function, and ADL
      disability status over 2 years. RESULTS: Every 10-kg increase in handgrip
      strength was associated with 5% decreased odds [odds ratio (OR): 0.95; 95%
      confidence interval (CI): 0.92, 0.98] of experiencing a lost IADL function in 2
      years. Likewise, every 10-kg increase in handgrip strength was associated with an
      8% decreased odds (OR: 0.92; CI: 0.88, 0.97) for 2-year onset ADL disability, 12%
      decreased odds (OR: 0.88; CI: 0.83, 0.94) for 2-year ADL disability progression,
      and 7% decreased odds (OR: 0.93; CI: 0.89, 0.98) for 2-year ADL disability
      improvement, compared to those with no ADL disability at baseline and follow-up.
      CONCLUSIONS: Higher muscle strength was related to a lower risk for 2-year onset
      of IADL and ADL disability in older Mexican Americans. Future investigations are
      warranted to examine how potential mediators influence the association between
      muscle strength and function, to inform interventions aiming to retain function
      in vulnerable older adult populations.

PMID- 29371126
TI  - A positive feedback loop between IL-1beta, LPS and NEU1 may promote
      atherosclerosis by enhancing a pro-inflammatory state in monocytes and
      macrophages.
AB  - Inflammation plays an important role in atherosclerosis, a notion supported by
      the beneficial effects of the IL-1beta inhibitor canakinumab in the CANTOS trial.
      Sialic acids (Sias), components of the surface glycocalyx, regulate intercellular
      and intermolecular interactions. We investigated the expression of the Sia
      cleaving enzyme neuraminidase-1 (NEU1) in atherosclerotic plaques and its
      potential role in inflammatory processes. In isolated mononuclear blood cells
      from patients with myocardial infarction, NEU1 expression was increased compared
      to healthy controls. High expression of NEU1 in macrophages located on the intima
      layer, in calcified regions and the adventitia of the plaque was observed in
      human carotid arteries' atherectomies. IL-1beta and LPS induced NEU1 expression
      in THP-1 monocytic cells. Lentiviral NEU1-overexpression in THP-1-cells enhanced
      expression of CD80, TNF-alpha, IL-1beta, number of multinuclear cells,
      phagocytosis and chemotaxis indicative for M1 monocyte/macrophage polarization.
      CRISPR/Cas9-mediated knock-out of NEU1 in THP-1-cells did not affect
      differentiation of monocytes to macrophages but attenuated LPS- and IL-1beta 
      induced TNF-alpha and IL-1beta expression. SiRNA-mediated knock-down of NEU1 in
      M1-macrophages differentiated from primary human CD14+ monocytes reduced the
      expression of TNF-alpha and IL-1beta. Thus, in monocytes/macrophages, LPS, NEU1
      and IL-1beta act in a positive feedback loop as enhancers of inflammation and may
      therefore promote atherosclerosis and plaque instability.

PMID- 29371127
TI  - Functional Status Is Associated With 30-Day Potentially Preventable Readmissions
      Following Skilled Nursing Facility Discharge Among Medicare Beneficiaries.
AB  - OBJECTIVES: The objectives of this study were to determine the association
      between patients' functional status at discharge from skilled nursing facility
      (SNF) care and 30-day potentially preventable hospital readmissions, and to
      examine common reasons for potentially preventable readmissions. DESIGN:
      Retrospective cohort study. SETTING: SNFs and acute care hospitals submitting
      claims to Medicare. PARTICIPANTS: National cohort of Medicare fee-for-service
      beneficiaries discharged from SNF care between July 15, 2013, and July 15, 2014
      (n = 693,808). Average age was 81.4 (SD 8.1) years, 67.1% were women, and 86.3%
      were non-Hispanic white. MEASUREMENTS: Functional items from the Minimum Data Set
      3.0 were categorized into self-care, mobility, and cognition domains. We used
      specifications for the SNF potentially preventable 30-day postdischarge
      readmission quality metric to identify potentially preventable readmissions.
      RESULTS: The overall observed rate of 30-day potentially preventable readmissions
      following SNF discharge was 5.7% (n = 39,318). All 3 functional domains were
      independently associated with potentially preventable readmissions in the
      multivariable models. Odds ratios for the most dependent category versus the
      least dependent category from multilevel models adjusted for patients'
      sociodemographic and clinical characteristics were as follows: mobility, 1.54
      (95% confidence interval [CI] 1.49-1.59); self-care, 1.50 (95% CI 1.44-1.55); and
      cognition, 1.12 (95% CI 1.04-1.20). The 5 most common conditions were congestive
      heart failure (n = 7654, 19.5%), septicemia (n = 7412, 18.9%), urinary tract
      infection/kidney infection (n = 4297, 10.9%), bacterial pneumonia (n = 3663,
      9.3%), and renal failure (n = 3587, 9.1%). Across all 3 functional domains,
      septicemia was the most common condition among the most dependent patients and
      congestive heart failure among the least dependent. CONCLUSIONS: Patients with
      functional limitations at SNF discharge are at increased risk of hospital
      readmissions considered potentially preventable. Future research is needed to
      determine whether improving functional status reduces risk of potentially
      preventable readmissions among this vulnerable population.

PMID- 29371129
TI  - Muscle Power Training: A Hallmark for Muscle Function Retaining in Frail Clinical
      Setting.

PMID- 29371131
TI  - Should the lungs be rested or open during anaesthesia to prevent postoperative
      complications?

PMID- 29371133
TI  - Hypertonic saline has a prolonged effect on mucociliary clearance in adults with
      cystic fibrosis.
AB  - BACKGROUND: Inhaled hypertonic saline (HS) has been shown to increase mucociliary
      clearance (MCC) and improve clinical outcomes in adults and adolescents with
      cystic fibrosis (CF). However, in younger children with CF, a large study failed
      to demonstrate clinical benefits. This discrepancy could reflect pharmacodynamic
      differences in the MCC response to HS in different populations. We previously
      demonstrated the absence of a sustained effect of HS on MCC in healthy adults and
      in this study sought to characterize the durability of the MCC response to HS in
      adults with CF. METHODS: At two study sites, MCC was measured in CF adults using
      gamma scintigraphy during three separate visits: at baseline, 15 min, and 4 h
      after a single dose of HS (7% NaCl, 4 mL). Particle clearance rates at these
      visits were used to assess the durability of the MCC response to HS. RESULTS: The
      average 90-minute clearance rate measured 4 h after HS was significantly
      increased (21.81% +/- 12.8) when compared to baseline (13.77% +/- 8.7, p = .048)
      and showed no apparent slowing relative to the rate measured 15 min after HS.
      While not all subjects responded to HS, the acute response strongly predicted the
      sustained effect in these subjects (r = 0.896, p < .0001). CONCLUSIONS: These
      results suggest that, in contrast to healthy adults, a single dose of HS has a
      prolonged effect on MCC in adults with CF, which lasts at least 4 h. This may
      explain its clinical efficacy in this population.

PMID- 29371130
TI  - Individualised perioperative open-lung approach versus standard protective
      ventilation in abdominal surgery (iPROVE): a randomised controlled trial.
AB  - BACKGROUND: The effects of individualised perioperative lung-protective
      ventilation (based on the open-lung approach [OLA]) on postoperative
      complications is unknown. We aimed to investigate the effects of intraoperative
      and postoperative ventilatory management in patients scheduled for abdominal
      surgery, compared with standard protective ventilation. METHODS: We did this
      prospective, multicentre, randomised controlled trial in 21 teaching hospitals in
      Spain. We enrolled patients who were aged 18 years or older, were scheduled to
      have abdominal surgery with an expected time of longer than 2 h, had intermediate
      to-high-risk of developing postoperative pulmonary complications, and who had a
      body-mass index less than 35 kg/m2. Patients were randomly assigned (1:1:1:1)
      online to receive one of four lung-protective ventilation strategies using low
      tidal volume plus positive end-expiratory pressure (PEEP): open-lung approach
      (OLA)-iCPAP (individualised intraoperative ventilation [individualised PEEP after
      a lung recruitment manoeuvre] plus individualised postoperative continuous
      positive airway pressure [CPAP]), OLA-CPAP (intraoperative individualised
      ventilation plus postoperative CPAP), STD-CPAP (standard intraoperative
      ventilation plus postoperative CPAP), or STD-O2 (standard intraoperative
      ventilation plus standard postoperative oxygen therapy). Patients were masked to
      treatment allocation. Investigators were not masked in the operating and
      postoperative rooms; after 24 h, data were given to a second investigator who was
      masked to allocations. The primary outcome was a composite of pulmonary and
      systemic complications during the first 7 postoperative days. We did the primary
      analysis using the modified intention-to-treat population. This trial is
      registered with ClinicalTrials.gov, number NCT02158923. FINDINGS: Between Jan 2,
      2015, and May 18, 2016, we enrolled 1012 eligible patients. Data were available
      for 967 patients, whom we included in the final analysis. Risk of pulmonary and
      systemic complications did not differ for patients in OLA-iCPAP (110 [46%] of
      241, relative risk 0.89 [95% CI 0.74-1.07; p=0.25]), OLA-CPAP (111 [47%] of 238,
      0.91 [0.76-1.09; p=0.35]), or STD-CPAP groups (118 [48%] of 244, 0.95 [0.80-1.14;
      p=0.65]) when compared with patients in the STD-O2 group (125 [51%] of 244).
      Intraoperatively, PEEP was increased in 69 (14%) of patients in the standard
      perioperative ventilation groups because of hypoxaemia, and no patients from
      either of the OLA groups required rescue manoeuvres. INTERPRETATION: In patients
      who have major abdominal surgery, the different perioperative open lung
      approaches tested in this study did not reduce the risk of postoperative
      complications when compared with standard lung-protective mechanical ventilation.
      FUNDING: Instituto de Salud Carlos III of the Spanish Ministry of Economy and
      Competitiveness, and Grants Programme of the European Society of Anaesthesiology.

PMID- 29371134
TI  - Pericytes constrict blood vessels after myocardial ischemia.
AB  - No-reflow phenomenon is defined as the reduced blood flow after myocardial
      ischemia. If prolonged it leads to profound damages in the myocardium. The lack
      of a detailed knowledge about the cells mediating no-reflow restricts the design
      of effective therapies. Recently, O'Farrell et al. (2017) by using state-of-the
      art technologies, including high-resolution confocal imaging in combination with
      myocardial ischemia/reperfusion mouse model, reveal that pericytes contribute to
      the no-reflow phenomenon post-ischemia in the heart. Strikingly, intravenous
      adenosine increased vascular diameter at pericyte site after cardiac ischemia.
      This study provides a novel therapeutic target to inhibit no-reflow phenomenon
      after myocardial ischemia.

PMID- 29371135
TI  - Localization of transcripts, translation, and degradation for spatiotemporal
      sarcomere maintenance.
AB  - The mechanisms responsible for maintaining macromolecular protein complexes, with
      their proper localization and subunit stoichiometry, are incompletely understood.
      Here we studied the maintenance of the sarcomere, the basic contractile
      macromolecular complex of cardiomyocytes. We performed single-cell analysis of
      cardiomyocytes using imaging of mRNA and protein synthesis, and demonstrate that
      three distinct mechanisms are responsible for the maintenance of the sarcomere:
      mRNAs encoding for sarcomeric proteins are localized to the sarcomere, ribosomes
      are localized to the sarcomere with localized sarcomeric protein translation, and
      finally, a localized E3 ubiquitin ligase allow efficient degradation of excess
      unincorporated sarcomeric proteins. We show that these mechanisms are distinct,
      required, and work in unison, to ensure both spatial localization, and to
      overcome the large variability in transcription. Cardiomyocytes simultaneously
      maintain all their sarcomeres using localized translation and degradation
      processes where proteins are continuously and locally synthesized at high rates,
      and excess proteins are continuously degraded.

PMID- 29371136
TI  - Reconstructed human epidermis models for irritant testing of medical devices.

PMID- 29371132
TI  - Integrated approaches to spatiotemporally directing angiogenesis in host and
      engineered tissues.
AB  - : The field of tissue engineering has turned towards biomimicry to solve the
      problem of tissue oxygenation and nutrient/waste exchange through the development
      of vasculature. Induction of angiogenesis and subsequent development of a
      vascular bed in engineered tissues is actively being pursued through combinations
      of physical and chemical cues, notably through the presentation of topographies
      and growth factors. Presenting angiogenic signals in a spatiotemporal fashion is
      beginning to generate improved vascular networks, which will allow for the
      creation of large and dense engineered tissues. This review provides a brief
      background on the cells, mechanisms, and molecules driving vascular development
      (including angiogenesis), followed by how biomaterials and growth factors can be
      used to direct vessel formation and maturation. Techniques to accomplish
      spatiotemporal control of vascularization include incorporation or encapsulation
      of growth factors, topographical engineering, and 3D bioprinting. The
      vascularization of engineered tissues and their application in angiogenic therapy
      in vivo is reviewed herein with an emphasis on the most densely vascularized
      tissue of the human body - the heart. STATEMENT OF SIGNIFICANCE: Vascularization
      is vital to wound healing and tissue regeneration, and development of
      hierarchical networks enables efficient nutrient transfer. In tissue engineering,
      vascularization is necessary to support physiologically dense engineered tissues,
      and thus the field seeks to induce vascular formation using biomaterials and
      chemical signals to provide appropriate, pro-angiogenic signals for cells. This
      review critically examines the materials and techniques used to generate
      scaffolds with spatiotemporal cues to direct vascularization in engineered and
      host tissues in vitro and in vivo. Assessment of the field's progress is intended
      to inspire vascular applications across all forms of tissue engineering with a
      specific focus on highlighting the nuances of cardiac tissue engineering for the
      greater regenerative medicine community.

PMID- 29371137
TI  - Human resources estimates and funding for antibiotic stewardship teams are
      urgently needed: authors' response.

PMID- 29371138
TI  - Treatment duration for Escherichia coli bloodstream infection and outcomes:
      retrospective single-centre study.
AB  - OBJECTIVES: To investigate the impact of treatment duration on mortality and on
      relapse in patients with Escherichia coli bloodstream infection (BSI). METHODS:
      Retrospective single-centre study of patients diagnosed with E. coli BSI at our
      centre over a 4-year period. EXCLUSION CRITERIA: age <18 years, clinical data not
      available, polymicrobial BSI, failure to receive in vitro active therapy, and
      death while receiving antibiotic therapy. Exposure variable was treatment
      duration dichotomized into short (<=10 days) and long (>10 days) therapy. Primary
      end point was all-cause mortality within 90 days after index BSI. Secondary end
      point was relapse, defined as repeat isolation of E. coli from blood cultures
      within 90 days after index BSI, in patients with documented clinical cure and
      completion of therapy for the initial episode. RESULTS: Of the 856 analysed
      patients: 426 received short and 430 received long therapy. All-cause mortality
      at day 90 occurred in 47 patients; on multivariate analysis, short therapy was
      not associated with a higher risk of mortality, also after adjusting the model
      for the propensity score of receiving short therapy. Relapse occurred in 42
      patients. Independent risk factors for relapse using death as competing risk were
      immunosuppression (subhazard ratio 4.67, p < 0.001), and end-stage liver disease
      (subhazard ratio 2.58, p 0.013). The propensity-weighted estimation of the
      average treatment effect for relapse reduction with long therapy (>10 days) was 
      1.6% (p 0.26) in the total population, and -7.1% (p 0.18) in immunocompromised
      patients. CONCLUSIONS: We could not identify shorter treatment duration as a risk
      factor for mortality and for relapse in patients with E. coli BSI.

PMID- 29371140
TI  - The Relationship Between Shift Work and Men's Health.
AB  - BACKGROUND: More than 21 million Americans and nearly 20% of the U.S. workforce
      are shift workers. Non-standard shift work, defined as work that falls outside of
      6 am-6 pm, can lead to poor diet, exercise, and sleep habits that lead to
      decreased productivity, increased workplace accidents, and a variety of negative
      health outcomes. AIM: To investigate the associations between shift work exposure
      and chronic medical conditions such as metabolic syndromes, cardiovascular
      disease, gastrointestinal disturbances, and depression as well as urologic
      complications including hypogonadism, male infertility, lower urinary tract
      symptoms, and prostate cancer with a focus on the effects of shift work sleep
      disorder (SWSD) on the severity of these negative health outcomes. METHODS: We
      reviewed the literature examining effects of shift work and SWSD on general and
      urologic health. OUTCOMES: We produced a summary of effects of shift work on
      health with focus on the increased risk of negative health outcomes in non
      standard shift workers, particularly those with SWSD, when compared to daytime
      workers or workers without SWSD. RESULTS: Studies have associated non-standard
      shift work schedules and poor health outcomes, including increased risks of
      diabetes mellitus, dyslipidemia, hypertension, heart disease, peptic ulcer
      disease, and depression, in shift workers. However, few studies have focused on
      the role that shift work plays in men's urologic health. Current evidence
      supports associations between non-standard shift work and increased hypogonadal
      symptoms, poor semen parameters, decreased fertility, lower urinary tract
      symptoms, and prostate cancer. These associations are strengthened by the
      presence of SWSD, which affects up to 20% of shift workers. Unfortunately,
      interventions, such as planned naps, timed light exposure, melatonin, and
      sedative hypnotics, aimed at alleviating excessive nighttime sleepiness and
      daytime insomnia in non-standard shift workers experiencing SWSD, are limited and
      lack strong evidence to support their efficacy. CONCLUSIONS: Non-standard shift
      work has been associated with a variety of negative health outcomes and urologic
      complications, especially with concurrent SWSD. Recognition of these increased
      risks among shift workers can potentially aid in more effective screening of
      chronic health and urologic conditions. Non-pharmacologic treatment of SWSD
      focuses on behavioral therapy and sleep hygiene while melatonin, hypnotics, and
      stimulants are used to alleviate insomnia and excessive sleepiness of SWSD.
      Further research into both pharmacologic and non-pharmacologic therapies for SWSD
      is needed to establish more definitive guidelines in the treatment of SWSD in
      order to increase productivity, minimize workplace accidents, and improve quality
      of life for shift workers. Deng N, Kohn TP, Lipshultz LI, et al. The Relationship
      Between Shift Work and Men's Health. Sex Med Rev 2018;6:446-456.

PMID- 29371139
TI  - The infant brain in the social world: Moving toward interactive social
      neuroscience with functional near-infrared spectroscopy.
AB  - Typically developing infants rapidly acquire a sophisticated array of social
      skills within the first year of life. These social skills are largely learned
      within the context of day-to-day interactions with caregivers. While social
      neuroscience has made great gains in our knowledge of the underlying neural
      circuitry of social cognition and behavior, much of this work has focused on
      experiments that sacrifice ecological validity for experimental control.
      Functional near-infrared spectroscopy (fNIRS) is a promising methodology for
      measuring brain activity in the context of naturalistic social interactions.
      Here, we review what we have learned from fNIRS studies that have used
      traditional experimental stimuli to study social development during infancy. We
      then discuss recent infant fNIRS studies that have utilized more naturalistic
      social stimuli, followed by a discussion of applications of this methodology to
      the study of atypical social development, with a focus on infants at risk for
      autism spectrum disorder. We end with recommendations for applying fNIRS to
      studies of typically developing and at-risk infants in naturalistic social
      situations.

PMID- 29371141
TI  - The Impact of Childhood Sexual Abuse on Women's Sexual Health: A Comprehensive
      Review.
AB  - INTRODUCTION: Childhood sexual abuse (CSA) has been identified as a potent risk
      factor for sexual dysfunction. Certain characteristics of the abuse experience,
      such as repeated abuse, appear to affect the risk of developing sexual
      dysfunction. Despite the robust findings that CSA can be detrimental to sexual
      function, there is little consensus on the exact mechanisms that lead to these
      difficulties. AIM: To summarize the most up-to-date research on the relation
      between CSA and women's sexual function. METHODS: The published literature
      examining the prevalence of sexual dysfunction among women with CSA histories,
      various types of sexual dysfunctions, and mechanisms proposed to explain the
      relation between CSA and later sexual difficulties was reviewed. MAIN OUTCOME
      MEASURES: Review of peer-reviewed literature. RESULTS: Women with abuse histories
      report higher rates of sexual dysfunction compared with their non-abused peers.
      The sexual concerns most commonly reported by women with abuse histories include
      problems with sexual desire and sexual arousal. Mechanisms that have been
      proposed to explain the relation between CSA and sexual dysfunction include
      cognitive associations with sexuality, sexual self-schemas, sympathetic nervous
      system activation, body image and esteem, and shame and guilt. CONCLUSION: Women
      with CSA histories represent a unique population in the sexual health literature.
      Review of mechanisms proposed to account for the relation between CSA and sexual
      health suggests that a lack of positive emotions related to sexuality, rather
      than greater negative emotions, appears to be more relevant to the sexual health
      of women with CSA histories. Treatment research has indicated that mindfulness
      based sex therapy and expressive writing treatments are particularly effective
      for this group. Further research is needed to clarify the mechanisms that lead to
      sexual dysfunction for women with abuse histories to provide more targeted
      treatments for sexual dysfunction among women with abuse histories. Pulverman CS,
      Kilimnik CD, Meston CM. The Impact of Childhood Sexual Abuse on Women's Sexual
      Health: A Comprehensive Review. Sex Med Rev 2018;6:188-200.

PMID- 29371142
TI  - Methodologic Considerations for the Study of Childhood Sexual Abuse in Sexual
      Health Outcome Research: A Comprehensive Review.
AB  - INTRODUCTION: Childhood sexual abuse (CSA) has been a topic of interest in sexual
      health research for decades, yet literature on the sexual health correlates of
      CSA has been hindered by methodologic inconsistencies that have resulted in
      discrepant samples and mixed results. AIM: To review the major methodologic
      inconsistencies in the field, explore the scientific and clinical impact of these
      inconsistencies, and propose methodologic approaches to increase consistency and
      generalizability to the general population of women with CSA histories. METHOD: A
      comprehensive literature review was conducted to assess the methodologic
      practices used in examining CSA and sexual health outcomes. MAIN OUTCOME
      MEASURES: Methodologic decisions of researchers examining sexual health outcomes
      of CSA. RESULTS: There are a number of inconsistencies in the methods used to
      examine CSA in sexual health research across the domains of CSA
      operationalization, recruitment language, and measurement approaches to CSA
      experiences. CONCLUSION: The examination of CSA and sexual health correlates is
      an important research endeavor that needs rigorous methodologic approaches. We
      propose recommendations to increase the utility of CSA research in sexual health.
      We recommend the use of a developmentally informed operationalization of
      childhood and adolescence, rather than age cutoffs. Researchers are encouraged to
      use a broad operationalization of sexual abuse such that different abuse
      characteristics can be measured, reported, and examined in the role of sexual
      health outcomes. We recommend inclusive recruitment approaches to capture the
      full range of CSA experiences and transparency in reporting these methods. The
      field also could benefit from the validation of existing self-report instruments
      for assessing CSA and detailed reporting of the instruments used in research
      studies. The use of more consistent research practices could improve the state of
      knowledge on the relation between CSA and sexual health. Kilimnik CD, Pulverman
      CS, Meston CM. Methodologic Considerations for the Study of Childhood Sexual
      Abuse in Sexual Health Outcome Research: A Comprehensive Review. Sex Med Rev
      2018;6:176-187.

PMID- 29371143
TI  - Surgical Factors Associated With Male and Female Sexual Dysfunction After Radical
      Cystectomy: What Do We Know and How Can We Improve Outcomes?
AB  - BACKGROUND: Sexual dysfunction after radical cystectomy (RC) is a frequent,
      though commonly overlooked symptom for both men and women. Improved oncological
      outcomes and the rising number of bladder cancer survivors mandate physicians to
      closely address and evaluate post-surgical sexual dysfunction and offer goal
      directed treatment. Improvements in RC surgical techniques that promote post
      operative sexual function have been proposed, alongside new quality-of-life
      inventories and sexual function therapeutic options; however, rigorous studies in
      the field are lacking. AIM: To provide a comprehensive overview of post-RC sexual
      dysfunction and discuss new surgical techniques, sexual dysfunction evaluation,
      and novel treatment strategies. METHODS: A non-systematic narrative review of the
      literature was performed through PubMed about sexual dysfunction in men and women
      after RC. OUTCOMES: We reported on the surgical anatomy of sexual function
      sparing RC, the most common inventories used to investigate sexual function in
      post-RC patients, and current treatment options. RESULTS: Extensive knowledge
      about pelvic anatomy and nerve-sparing surgical techniques in men is well
      understood from studies about prostate anatomy and nerve-sparing prostatectomy.
      However, anatomical and surgical details of sexual-sparing RC in women needs
      further characterization. Several questionnaires are used to investigate
      sexuality after RC, but a standardized approach is still missing. Therapeutic
      options are available to treat sexual dysfunction, but limited studies have been
      conducted to specifically address the post-RC population. CONCLUSION: Further
      work is needed to understand the best strategies to prevent and treat sexual
      dysfunction in patients after RC. Pederzoli F, Campbell JD, Matsui H, et al.
      Surgical Factors Associated With Male and Female Sexual Dysfunction After Radical
      Cystectomy: What Do We Know and How Can We Improve Outcomes? Sex Med Rev
      2018;6:469-481.

PMID- 29371145
TI  - Assessment of Sexual Desire for Clinical Trials of Women With Hypoactive Sexual
      Desire Disorder: Measures, Desire-Related Behavior, and Assessment of Clinical
      Significance.
AB  - BACKGROUND: The Female Sexual Function Index-desire subscale is the standard
      measure for clinical trials of hypoactive sexual desire disorder (HSDD), but
      lacks items assessing sexually related behaviors and attitudes toward partner.
      Counting satisfying sexual events is criticized, but sexual behavior remains
      important. Mean treatment differences cannot define clinical significance;
      responder and remitter analyses help. We reviewed measures on sexual desire and
      sexual behavior relevant to HSDD, and how to assess clinical significance.
      METHODS: We conducted a literature review of measures of sexual desire comparing
      expert-proposed criteria for dysfunctional desire, expert-developed scales, and
      scales from patient input. Commonly recognized symptoms of HSDD were identified.
      Results of HSDD trials and scale validation studies were evaluated to extract
      responder and remitter values. The utility of distribution-based measures of
      responders and remitters was assessed. OUTCOMES: Symptom relevance was evaluated
      as the proportion of symptom sets that included the item; responder and remitter
      cut points were determined by distribution-based methods. RESULTS: 12 Validated
      rating scales, 5 scales primarily derived from expert recommendations and 7
      scales initially from patient input, and 5 sets of diagnostic criteria for
      conditions like HSDD were compared. Content varied highly between scales despite
      compliance with U.S. Food and Drug Administration recommendations for patient
      reported outcomes. This disunity favors an expert-recommended scale such as the
      Elements of Desire Questionnaire with each of the common items, plus a measure of
      frequency of sexual activity, eg, item in the Patient Reported Outcomes
      Measurement Information System. Registrational drug trials, but not psychological
      treatment trials, usually give responder/remitter analyses, using dichotomized
      global impressions or anchor-based definitions. Distribution-based methods are
      more uniformly applicable to define responder and remitter status. CONCLUSIONS:
      The Female Sexual Function Index-desire subscale measures the most relevant
      element of sexual desire, but it would be meaningful to include 4 or 5 more
      sexual symptoms as end points: sexual thoughts/fantasies, frequency of sexual
      activity, receptivity, initiations, and possibly avoidance of sexual situations.
      The Elements of Desire Questionnaire and a measure of sexual frequency may
      suffice. Responder and remitter analyses show the clinical relevance of a
      treatment and enable comparisons across trials. Pyke RE, Clayton AH. Assessment
      of Sexual Desire for Clinical Trials of Women With Hypoactive Sexual Desire
      Disorder: Measures, Desire-Related Behavior, and Assessment of Clinical
      Significance. Sex Med Rev 2018;6:367-383.

PMID- 29371144
TI  - Traditional Chinese Medicine for Sexual Dysfunction: Review of the Evidence.
AB  - INTRODUCTION: Despite the growing popularity of traditional Chinese medicine
      (TCM) in the Western world, biomedical students and practitioners struggle to
      understand TCM and how it relates to their standard diagnosis and treatment
      practices. AIMS: To describe the fundamentals of TCM theory and practice relevant
      to sexual dysfunction; to review and critique the current state of TCM research
      within Western biomedical literature; and to identify sites for improvement of
      future research and for collaborative integration of TCM and biomedicine in
      practice. METHODS: Information about TCM from an insider perspective was obtained
      from English-language textbooks and lectures intended to teach Western students
      its theory and practice. PubMed search using Medical Subject Heading terms for
      Western sexual diagnoses and TCM treatments was performed in April and October
      2017 to represent the evidence for TCM in Western biomedical literature. Articles
      in non-English languages and without human subjects were excluded. MAIN OUTCOME
      MEASURES: 27 studies were included in this review. The most commonly studied
      intervention was acupuncture. An equal number of studies addressed sexual
      dysfunction in men and women, but only women were included in studies of
      physically passive mindfulness meditation. RESULTS: Compared with Western
      biomedicine, TCM offers a more interdisciplinary and individualized approach to
      disease and its treatment. This embrace of individual idiosyncrasy in diagnosis
      and treatment presents a challenge to Western biomedical research norms that rely
      almost exclusively on quantitative methods that compare large and homogeneous
      groups with a fixed diagnosis and treatment regimen. CONCLUSION: TCM offers a
      very different understanding of the human body, health, and disease from Western
      biomedicine. There is value in the study and application of these 2 medical
      systems, particularly for biopsychosocial problems of sexual dysfunction.
      However, this must be done cautiously, with attention to appropriate study
      design, to avoid shallow and unscientific cultural appropriation of TCM
      practices. Chubak B, Doctor A. Traditional Chinese Medicine for Sexual
      Dysfunction: Review of the Evidence. Sex Med Rev 2018;6:410-418.

PMID- 29371146
TI  - Couplepause: A New Paradigm in Treating Sexual Dysfunction During Menopause and
      Andropause.
AB  - BACKGROUND: At midlife and beyond, both men and women face organic changes that
      can affect sexual functioning. For women, ovarian exhaustion causes estrogen
      deficiency, leading to genitourinary syndrome of menopause, which may include
      vaginal dryness, irritation/itching, inadequate lubrication, and dyspareunia.
      Hypoactive sexual desire disorder also can result from biopsychosocial factors.
      For men, erectile dysfunction prevalence increases with age, and some men develop
      testosterone deficiency. AIM: In this narrative review, we summarize the
      literature on how menopause and andropause can affect the sexual health of both
      the patient and partner and describe a new paradigm ("couplepause") for
      addressing the sexual health needs of the aging couple as a whole. METHODS: We
      combined a literature review conducted using PubMed with insights garnered from
      our own clinical experiences. OUTCOMES: We reviewed publications relating to
      couples-based approaches to sexual dysfunction, male perceptions of female sexual
      dysfunction, female perceptions of male sexual dysfunction, interactions between
      male and female sexual dysfunctions, sexual dysfunction and midlife changes in
      homosexual couples, and impact of pharmacologic treatments for sexual
      dysfunctions on the couple's sexual health. RESULTS: Both members of a couple may
      experience age-related changes concurrently and interdependently. In such cases,
      it is unhelpful, and sometimes detrimental, to treat the symptoms for only one
      member of the couple without also treating the other. Therefore, as an evolution
      of the couple-oriented approaches of Masters and Johnson and others, we introduce
      the concept of couplepause and the need for a new diagnostic and therapeutic
      paradigm that addresses the sexual health needs of the aging couple as a whole
      rather than treating the individual patient in isolation. CONCLUSION: Taking a
      couple-oriented approach to evaluate and manage couplepause in the latter half of
      life can dramatically and simultaneously help both members of the couple to
      improve sexual satisfaction and intimacy. Jannini EA, Nappi RE. Couplepause: A
      New Paradigm in Treating Sexual Dysfunction During Menopause and Andropause. Sex
      Med Rev 2018;6:384-395.

PMID- 29371147
TI  - A small heat shock protein 21 (sHSP21) mediates immune responses in Chinese oak
      silkworm Antheraea pernyi.
AB  - Small heat shock proteins (sHSPs) are conserved among insects and play an
      important role in the regulation of many biological processes, including
      temperature stress, abiotic stress, immune responses, metamorphosis, and embryo
      development. Antheraea pernyi is an economically valuable silk-producing moth and
      source of insect food containing high-quality protein. The aim of this study was
      to quantify expression of the ApsHSP21 gene in response to pathogen-associated
      molecular patterns (PAMPs) and nucleopolyhedrovirus (NPV) challenge. The deduced
      ApsHSP21 protein sequence consists of 186 residues with a calculated molecular
      mass of 21.0 kDa and an isoelectronic point (pI) of 6.63. The protein contains a
      conserved alpha-crystallin domain (ACD), and includes two casein kinase II
      phosphorylation sites, a protein kinase C phosphorylation site, two tyrosine
      kinase phosphorylation sites, and various polypeptide binding sites. Phylogenetic
      analysis revealed that ApsHSP21 is closely related to homologs from other
      insects. Real-time quantitative reverse transcription PCR (qRT-PCR) analysis
      revealed that expression of ApsHSP21 was significantly up-regulated at different
      timepoints following simulated pathogen challenge with lipopolysaccharide (LPS),
      peptidoglycan (PGN), glucan, and NPV. The results suggest sHSP21 is involved in
      innate immune responses in A. pernyi.

PMID- 29371148
TI  - Structural and enzymatic analysis of the cytochrome b5 reductase domain of Ulva
      prolifera nitrate reductase.
AB  - Rapid accumulations of unattached green macroalgae, referred to as blooms,
      constitute ecological disasters and occur in many coastal regions. Ulva are a
      major cause of blooms, owing to their high nitrogen utilization capacity, which
      requires nitrate reductase (NR) activity; however, molecular characterization of
      Ulva NR remains lacking. Herein we determined the crystal structure and performed
      an enzymatic analysis of the cytochrome b5 reductase domain of Ulva prolifera NR
      (UpCbRNR). The structural analysis revealed an N-terminal FAD-binding domain
      primarily consisting of six antiparallel beta strands, a C-terminal NADH-binding
      domain forming a Rossmann fold, and a three beta-stranded linker region
      connecting these two domains. The FAD cofactor was located in the cleft between
      the two domains and interacted primarily with the FAD-binding domain. UpCbRNR
      shares similarities in overall structure and cofactor interactions with homologs,
      and its catalytic ability is comparable to that of higher plant CbRNRs. Structure
      and sequence comparisons of homologs revealed two regions of sequence length
      variation potentially useful for phylogenetic analysis: one in the FAD-binding
      domain, specific to U. prolifera, and another in the linker region that may be
      used to differentiate between plant, fungi, and animal homologs. Our data will
      facilitate molecular-level understanding of nitrate assimilation in Ulva.

PMID- 29371149
TI  - Redox-responsive micelles for triggered drug delivery and effective
      laryngopharyngeal cancer therapy.
AB  - In this study, we reported a redox-responsive drug delivery system (DDS) based on
      heparosan and deoxycholic acid conjugates (HSDs) for effective treatment of
      laryngopharyngeal carcinoma. The amphiphilic HSDs can self-assemble into stable
      nanoscale micelles in aqueous medium with favorable drug loading capacity for
      doxorubicin (DOX). The HSD micelles can exhibit glutathione (GSH)-triggered drug
      release behavior and reach a nearly 100% release rate in a high GSH level (10 mM)
      environment. Moreover, FaDu cancer cells can internalize HSD micelles by clathrin
      mediated endocytosis, which is energy dependent, fast, and effective. The DOX@HSD
      induced inhibition of FaDu cancer cells can achieve a minimum of 10-fold
      selectivity relative to that of COS-7 normal cells. Overall, the redox-responsive
      DDSs show good biocompatibility and are promising in the clinical treatment of
      laryngopharyngeal carcinoma.

PMID- 29371150
TI  - Synthetic biology approaches: Towards sustainable exploitation of marine
      bioactive molecules.
AB  - The discovery of genes responsible for the production of bioactive metabolites
      via metabolic pathways combined with the advances in synthetic biology tools, has
      allowed the establishment of numerous microbial cell factories, for instance the
      yeast cell factories, for the manufacture of highly useful metabolites from
      renewable biomass. Genome mining and metagenomics are two platforms provide base
      line data for reconstruction of genomes and metabolomes which is based in the
      development of synthetic/semi-synthetic genomes for marine natural products
      discovery. Engineered biofilms are being innovated on synthetic biology platform
      using genetic circuits and cell signalling systems as represillators controlling
      biofilm formation. Recombineering is a process of homologous recombination
      mediated genetic engineering, includes insertion, deletion or modification of any
      sequence specifically. Although this discipline considered new to the scientific
      domain, this field has now developed as promising endeavor on the accomplishment
      of sustainable exploitation of marine natural products.

PMID- 29371151
TI  - Extraction optimization, characterization, antioxidant and immunomodulatory
      activities of a novel polysaccharide from the wild mushroom Paxillus involutus.
AB  - Response surface methodology (RSM) using a Box-Behnken design (BBD) was applied
      to optimize the extraction of Paxillus involutus polysaccharides. The optimum
      conditions included an extraction time of 3h, extraction temperature of 79
      degrees C and a ratio of liquid to raw material of 43.1mL/g. Under the optimized
      conditions, the polysaccharides yield was 12.25%. Then, the polysaccharides were
      purified with DEAE-Cellulose 52 and Sephadex G-100 gel columns, and the fraction
      denoted as PIP2-1 with a molecular weight of 32kDa was obtained. PIP2-1 was
      composed of mannose, glucose, galactose, fucose with the mole percentages of
      2.8%, 62.2%, 25.4% and 9.6%. The PIP2-1 possessed typical Fourier Transform
      infrared spectroscopy (FTIR) characterization of polysaccharides. The methylation
      analysis showed that the PIP2-1 mainly included 1-linked-fuc, 1,3-linked-man, 1
      linked-glc, 1,4-linked-glc, 1,6-linked-glc, 1-linked-gal, 1,6-linked-gal, 1,4,6
      linked-gal and 1,2,6-gal glycosidic bonds. Furthermore, PIP2-1 showed significant
      antioxidant activity against hydroxyl radicals (OH), 1,1-diphenyl-2
      picrylhydrazyl radicals (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic
      acid (ABTS) and superoxide radicals. Finally, PIP2-1 significantly enhanced the
      release of TNF-alpha and IL-6 in RAW264.7 cells. The results indicated that PIP2
      1 could be exploited as a natural antioxidant and immunomodulator for functional
      food and medical applications.

PMID- 29371152
TI  - The performance of immobilized Candida rugosa lipase on various surface modified
      graphene oxide nanosheets.
AB  - In this study, we have reported the synthesis of graphene oxide nanosheets (GON)
      and its functionalization with 2, 4, 6-trichloro-1, 3, 5-triazine (TCT) through
      two routes, (a) directly reaction of GON with TCT (GON-1), and (b) reaction of
      GON with pre-functionalized TCT with 3-aminopropyltriethoxysilane (APTS) (GON-2).
      Subsequently, GON, GON-1 and GON-2 have been used as supports for immobilization
      of Candida rugosa lipase (CRL). Several techniques such as XRD, SEM, EDS, UV-Vis,
      CHNS, FTIR and AFM were applied to characterize the nano-structures and success
      of synthesis, functionalization and CRL immobilization processes. The results
      corresponding to optimization of immobilization process revealed the following
      order for values of loading capacity, immobilization yield and leaching of CRL:
      GON > GON-1 > GON-2, while this order is reversed for, specific activity and
      recovery activity. The assessment of operational parameters represents the high
      storage stability and reasonable reusability for all the immobilized CRL while
      the pH and thermal stability of CRL@GON-2 are higher than two others. It seems
      the longer linker of GON-2 could more effectively prevent the unfavorable
      interaction between enzyme-enzyme and enzyme-product that consequently resulted
      the best catalytic performance, pH and thermal stability. The advantages of these
      supports make them suitable candidates for practical applications.

PMID- 29371153
TI  - Pilus-encoding islets in S. agalactiae and its association with antibacterial
      resistance and serotype distribution.
AB  - Group B Streptococcus (GBS) is a versatile organism which uses multiple virulence
      factors which bind to the surface of epithelial cells. Pili are one of virulence
      factors detected in recent years. A total of 90 isolates were collected from
      invasive and non-invasive isolates among adults throughout 2014-2015. Isolates
      were serotyped at molecular level based on capsular polysaccharide (cps)
      serotyping and analyzed for pilus island profiles, scpB gene, and hvgA gene
      presence. Isolates were subjected to antimicrobial susceptibility towards
      penicillin, tetracycline, erythromycin, clindamycin, moxifloxacin, levofloxacin,
      and vancomycin by disk diffusion method and MICs for erythromycin and clindamycin
      were determined by broth dilution methods. Overall, 4 serotypes were identified,
      serotype III (68.88%), V (20%), II (10%) and Ib (1.11%) and hvgA gene was
      detected in 7.7% (n = 7) of the isolates; all were serotype III/ST 17. All
      isolates were susceptible to penicillin and vancomycin, except one isolate which
      showed intermediate resistance to penicillin and other complete resistance to
      vancomycin. Isolates were resistant to tetracycline (98%), erythromycin (25%),
      clindamycin (22%), moxifloxacin (8%), and levofloxacin (6%). The scpB gene was
      detected in all isolates, while isolates harbored at least one PI, of which the
      PI-1+PI-2a was the most frequent combination observed. Our data show the presence
      of the relation between serotype or pilus genes among clinical isolates of
      Streptococcus agalactiae. These data are principal to help in designing
      prevention and treatment strategies for GBS infections in the region.

PMID- 29371154
TI  - Trypanosoma brucei bloodstream forms express highly specific and separate
      transporters for adenine and hypoxanthine; evidence for a new protozoan purine
      transporter family?
AB  - The transport of nucleobases and nucleosides in protozoan parasites is known to
      be performed by Equilibrative Nucleoside Transporter (ENT) family members,
      including the extensively studied P1 and P2 nucleoside transporters of T. brucei
      bloodstream forms. Studies with P2 knockout parasites suggested the existence of
      as yet uncharacterised purine transport mechanisms in these cells. Here, we
      deleted several ENT genes, in addition to P2, including an array comprising three
      genes encoding for high-affinity broad-selectivity nucleobase transporters - the
      longest multi-gene locus deletion in T. brucei to date. It was verified that none
      of them appreciably contributed to the transport of hypoxanthine in bloodstream
      forms grown axenically in HMI-9 medium, which was mainly performed by a
      previously not described hypoxanthine-specific transporter (HXT1) with a Km of 22
      +/- 1.7 MUM and Vmax of 0.49 +/- 0.06 pmol(107 cells)-1 s-1. The uptake of
      adenine was also assessed in the knockout cells and was performed by a highly
      specific adenine transporter (ADET1) with a Km of 573 +/- 62 nM and Vmax of 0.23
      +/- 0.06 pmol(107 cells)-1 s-1. Neither HXT1 nor ADET1 displayed any affinity for
      other natural purines or pyrimidines and could not be completely inhibited by
      hypoxanthine or adenine analogues. These carriers may be the final pieces in the
      substantial transporter array trypanosomes can employ to fine-tune the uptake of
      purines from diverse environments during their life cycles, and may be encoded by
      genes other than those of the ENT family.

PMID- 29371155
TI  - SOX2: Not always eye malformations. Severe genital but no major ocular anomalies
      in a female patient with the recurrent c.70del20 variant.
AB  - SOX2 variants have been identified in multiple patients with severe ocular
      anomalies and pituitary dysfunction, in addition to various systemic features. We
      investigated a 26-year-old female patient suffering from spastic paraparesis,
      hypoplasia of corpus callosum, hypogonadotropic hypogonadism (HH) and
      intellectual disability, who was monitored for over 20 years, allowing a detailed
      genotype-phenotype correlation along time. Whole exome sequencing on the patient
      and her relatives identified a de novo SOX2 c.70del20 variant, which has been
      frequently reported in individuals with SOX2-related anophthalmia. Importantly,
      our patient lacked major ocular phenotype but showed vaginal agenesis, a feature
      never reported before. Although the involvement of male urogenital tract
      (cryptorchidism, hypospadias, small penis), is a well known consequence of SOX2
      variants, their effect on the female genitalia has never been properly addressed,
      even considering the paradoxical female excess of SOX2 cases in the literature.
      Our findings emphasize the importance of testing for SOX2 variants in individuals
      with HH and genital anomalies even though anophthalmia or microphthalmia are not
      observed. Moreover, our case strengthens the role of SOX2 as a master regulator
      of female gonadal differentiation, as widely demonstrated for other SOX genes
      related to 46, XX sex reversal, such as SOX3 and SOX9.

PMID- 29371156
TI  - One Thing after Another: Ecthyma Gangrenosum.

PMID- 29371157
TI  - Do We Learn More from Our Mistakes than from Our Successes?

PMID- 29371158
TI  - Brain Tumors.
AB  - Brain tumors are common, requiring general medical providers to have a basic
      understanding of their diagnosis and management. The most prevalent brain tumors
      are intracranial metastases from systemic cancers, meningiomas, and gliomas,
      specifically, glioblastoma. Central nervous system metastases may occur anywhere
      along the neuroaxis, and require complex multidisciplinary care with
      neurosurgery, radiation oncology, and medical oncology. Meningiomas are tumors of
      the meninges, mostly benign and often managed by surgical resection, with
      radiation therapy and chemotherapy reserved for high-risk or refractory disease.
      Glioblastoma is the most common and aggressive malignant primary brain tumor,
      with a limited response to standard-of-care concurrent chemoradiation. The new
      classification of gliomas relies on molecular features, as well as histology, to
      arrive at an "integrated diagnosis" that better captures prognosis. This
      manuscript will review the most common brain tumors with an emphasis on their
      diagnosis, oncologic management, and management of medical complications.

PMID- 29371159
TI  - Flavonoid glycosides and alkaloids from the embryos of Nelumbo nucifera seeds and
      their antioxidant activity.
AB  - Chemical investigation of the embryos of Nelumbo nucifera afforded four new
      flavone C-glycosides, named nelumbosides A-D (1-4), together with nine known
      ones, comprising five flavonoids (5-9) and four alkaloids (10-13). The chemical
      structures of the new compounds were elucidated by 1D, 2D-NMR and HR-ESI-MS
      techniques, together with chemical methods. Nelumbosides A-D (1-4) are rarely
      present in naturally occurring flavone C-glycosides featuring a 4-hydroxystyrene
      unit connected to the flavonoid skeleton. Compounds 2-13 were evaluated for their
      antioxidant activity by ABTS and DPPH radical-scavenging assay. Among them,
      compounds 2, 6, 7 and 11 exhibited strong scavenging activity with SC50 values
      ranging from 12.07 to 25.68MUM compared with the positive control l-ascorbic
      acid.

PMID- 29371160
TI  - Chiral resolution and bioactivity of enantiomeric benzofuran neolignans from the
      fruit of Rubus ideaus L.
AB  - Rubus ideaus L., a member of the Rosaceae family, is popular for its distinctive
      flavor and attractive red color. In order to explore the functional factors
      possibly presented in the fruit, seven new benzofuran neolignans (1a/1b-3a/3b and
      4b), together with one known neolignan 4a, were isolated from the fruit of R.
      ideaus. Compounds 1a/1b-4a/4b as four pairs of enantiomers were separated on a
      chiral chromatographic column. Their structures including absolute configurations
      were elucidated by extensive spectroscopic data analyses, including UV, IR,
      HRESIMS, NMR, and comparing their experimental electronic circular dichroism
      (ECD) spectra with calculated ECD spectra. Additionally, all these enantiomeric
      compounds were evaluated for their antioxidant, neuroprotective, and anti-Abeta1
      42 aggregation activities.

PMID- 29371161
TI  - Emergency Department Switching and Duplicate Computed Tomography Scans in
      Patients With Kidney Stones.
AB  - OBJECTIVE: To test whether duplicate imaging relates to a lack of information
      sharing among providers, we measured the association between emergency department
      (ED) switching during a kidney stone episode and receipt of a repeat computed
      tomography (CT) scan. METHODS: Using the MarketScan Commercial Claims and
      Encounters Database, we identified adults between the ages 18 and 64 with an ED
      visit for a diagnosis of kidney stones. Among patients who had an abdominal or
      pelvic CT scan at their initial encounter, we then determined the subset that
      made an ED revisit within 30 days of their first, distinguishing between those to
      the same vs a different ED. Finally, we fit multivariable logistic regression
      models to estimate the risk of receiving a repeat CT scan associated with ED
      switching. RESULTS: Twelve percent of patients who received a CT scan at their
      initial ED encounter had a revisit within 30 days of discharge. One-third of
      their revisits were made to a different ED than the index one. Duplicate CT scans
      were obtained at nearly 40% of all revisits. On multivariable analysis, the risk
      of receiving a repeat CT was 12% higher if this revisit was made to a different
      ED (risk ratio, 1.12; 95% confidence interval, 1.03-1.21; P = .010). CONCLUSION:
      Our study reveals that ED switching during an acute kidney stone episode is
      associated with higher levels of repeat CT imaging. These findings support the
      role of better health information exchange among providers to help reduce waste
      in the health-care system.

PMID- 29371162
TI  - Associations of Intraoperative Flow Disruptions and Operating Room Teamwork
      During Robotic-assisted Radical Prostatectomy.
AB  - OBJECTIVE: To identify type and severity of surgical flow disruptions and to
      determine their impact on the perception of intraoperative teamwork. METHODS:
      Forty radical prostatectomy cases were studied in an academic department for
      urology. A standardized observational tool for identification of type and
      severity of flow disruptions was applied during real-time prostatectomy
      procedures. Additionally, all operating room team members evaluated
      intraoperative teamwork immediately after the procedure. Procedures were divided
      into 4 phases: prerobot, docking, console time, and postrobot. RESULTS: A total
      of 2012 flow disruptions were observed, with an average rate of 16.27 events per
      hour. The highest rate was during the robot docking phase. Although the frequency
      of disruption types varied across phases, the most severe disruptions were
      related to communication and coordination during the prerobot and docking phase.
      Equipment- and communication-related disruptions were mostly severe during the
      time the surgeons were on the console. Among the surgeons, we identified a
      significant relationship between disruptions and intraoperative teamwork such
      that during procedures with frequent severe disruptions, surgeons experienced
      inferior teamwork (beta = -0.40, P = .01). This was not the case for nurses and
      anesthetists. CONCLUSION: Emphasis on improving operating room team communication
      and coordination would help to establish efficient and smooth surgical workflow.

PMID- 29371163
TI  - Letter to the Editor on the article "Endoscopic resection versus radical
      gastrectomy for early gastric cancer in Asia: A meta-analysis".

PMID- 29371164
TI  - Anti-inflammatory effect of avenanthramides via NF-kappaB pathways in C2C12
      skeletal muscle cells.
AB  - Avenanthramides (Avns), the polyphenol compounds found only in oats, have been
      shown to exhibit anti-inflammatory effects mainly by inhibiting nuclear factor
      (NF)-kappaB activation in select cell lines. However, the molecular mechanism by
      which Avns regulate the NF-kappaB pathway is still unclear. The purpose of this
      study was to investigate (1) the molecular mechanism by which three main
      fractions of Avns (AvnA, AvnB and AvnC) interact with IkappaB Kinase beta
      (IKKbeta); and (2) whether this interaction results in reduced inflammatory
      responses in skeletal muscle cells. The protein-ligand docking and molecular
      dynamics simulation studies suggest that Avns acted as an allosteric inhibitor
      for modulating IKKbeta's affinity for the NF-kappaB complex. Thus, Avns reduced
      IKKbeta kinase activity in response to tert-butyl hydroperoxide (tBHP)
      stimulation and attenuated tBHP-induced TNFalpha and IL-1beta mRNA expression.
      Furthermore, the three-fold increases in cyclooxygenase-2 (COX-2) protein and
      luciferase activity with tBHP treatment were reduced by 50% with Avns (P < .01),
      along with decreased prostaglandin E2 levels (P < .01). These data indicate that
      Avns are potent inhibitors of NFkappaB-mediated inflammatory response due to the
      downregulation of IKKbeta activity in C2C12 cells.

PMID- 29371165
TI  - Occipital Artery to Middle Cerebral Artery Bypass in Cases of Unavailable
      Superficial Temporal Artery.
AB  - In neurosurgery, extracranial-to-intracranial (EC-IC) bypass surgery is necessary
      for patients who have undergone surgery in which the superficial temporal artery
      (STA) was already used for a different bypass procedure or was damaged. Here we
      report our experience with EC-IC bypass using the occipital artery (OA) in
      patients in whom the STA was unavailable, and discuss the technical
      considerations and pitfalls. Five patients with ischemic-onset moyamoya disease
      and atherosclerotic disease were included. Two patterns of skin incisions were
      planned according to the OA pathway and recipient artery location. In one of
      these methods, a skin incision is made above the OA, and a craniotomy is
      performed under this incision after OA dissection. In the other method, a skin
      incision is made above the OA to enable its dissection, and a craniotomy is
      performed via a separate skin incision. No major perioperative complications
      developed in any of the 5 cases, and bypass patency was confirmed in all
      patients. There was a significant difference between the preoperative and
      postoperative asymmetry ratios of the mean transit time values. Our findings
      suggest that OA-to-middle cerebral artery (MCA) bypass is a simple and effective
      technique in patients in whom the STA was already used or was damaged by previous
      intracranial revascularization or craniotomy. This procedure could be an
      alternative to STA-MCA bypass in patients without an available STA.

PMID- 29371166
TI  - Neuroendoscopic Fenestration for Entrapped Temporal Horn After Surgery: Report of
      3 Cases.
AB  - BACKGROUND: The postoperative ventricular adhesion after resection of central
      nervous system tumors can obstruct physiologic cerebrospinal fluid (CSF)
      circulation and cause temporal horn entrapment. The surgical goal is to restore
      physiologic flow of CSF. The authors reviewed their database to report their
      experience with endoscopic fenestration for treating entrapped temporal horn
      caused by atrial adhesions. All endoscopic operations performed from February
      2015 to December 2016 were reviewed. CASE DESCRIPTION: Three patients developed
      temporal horn entrapment after tumor resection. Fenestration was successful in
      all patients, with a subsequent stomy of the septum pellucidum. Follow-up
      magnetic resonance imaging 1 year later showed a patent reduction of the
      entrapped horn. CONCLUSIONS: Endoscopic fenestration is an option in the
      treatment of entrapped temporal horns. However, more experience is required to
      recommend it as the treatment of choice.

PMID- 29371167
TI  - Making Anatomic Preparations of the Human Brain Using Colored Silicone for
      Vascular Perfusion Staining (Technical Description).
AB  - BACKGROUND: A thorough understanding of the central nervous system anatomy is a
      fundamental part of a neurosurgeon's training. Development of novel neurosurgical
      approaches and optimization of existing ones directly depend on the comprehensive
      study of topographic anatomy of the head and neck using cadaveric specimens.
      Staining the vessels of the arterial and venous systems of a cadaveric specimen
      aids a detailed study of the vascularization of anatomic structures of the brain.
      Here we describe an alternative expedited method for creating anatomic
      preparations of the human brain using colored silicone for vascular perfusion
      staining. METHODS: A nonfixed, whole cadaver (with the head intact), without
      central nervous system pathology, no later than 48 hours after death, is used to
      prepare the human brain specimen through staining of arterial and venous vessels.
      RESULTS: Our proposed method provides a fast and inexpensive approach to making
      anatomic preparations of the human brain with staining of the vascular system.
      The preparations thus obtained can be used for educational purposes, aiding the
      study of normal and topographic anatomy of the brain, as well as the development
      of new microsurgical and/or endoscopic approaches. CONCLUSIONS: In experienced
      hands, our proposed method allows the creation of anatomic preparations
      relatively fast, at low cost, and with excellent quality.

PMID- 29371168
TI  - Accuracy of Susceptibility-Weighted Imaging and Dynamic Susceptibility Contrast
      Magnetic Resonance Imaging for Differentiating High-Grade Glioma from Primary
      Central Nervous System Lymphomas: Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: It is always a great challenge to distinguish high-grade
      glioma (HGG) from primary central nervous system lymphoma (PCNSL). We conducted a
      meta-analysis to assess the performance of dynamic susceptibility contrast (DSC)
      and susceptibility-weighted imaging (SWI) in differentiating HGGs from PCNSLs.
      METHODS: Heterogeneity and threshold effect were evaluated, and sensitivity,
      specificity (SPE), and areas under the summary receiver operating characteristic
      curve (SROC) were calculated. RESULTS: Thirteen studies with a total of 704
      participants were included in this meta-analysis. For the dynamic susceptibility
      contrast (DSC) technique, the pooled sensitivity and SPE were 0.94 and 0.84,
      respectively. The area under the curve (AUC) under the SROC was 0.9595, and the
      diagnostic odds ratio was 81.880. For the susceptibility weighted imaging (SWI)
      technique, the pooled sensitivity and SPE were 0.92 and 0.87, respectively. The
      AUC under the SROC was 0.9608, and the diagnostic odds ratio was 89.774. A Z test
      showed that no significant difference in AUC values between DSC and SWI (P =
      0.97) was observed. In addition, no obvious public bias was observed in both the
      DSC (P = 0.69) and SWI (P = 0.32) groups. CONCLUSIONS: This meta-analysis
      indicated that both DSC-MRI and SWI have a high and similar level of diagnostic
      accuracy for differentiating HGGs from PCNSLs.

PMID- 29371169
TI  - Early Stereotactic Radiosurgery for Medically Refractory Trigeminal Neuralgia.
AB  - OBJECTIVE: To evaluate effectiveness of early Gamma Knife radiosurgery (GKRS) in
      treatment of medically refractory trigeminal neuralgia (TN). METHODS: This
      retrospective review comprised 108 consecutive patients with medically refractory
      idiopathic TN between 2006 and 2014. All patients underwent GKRS targeting the
      root entry zone with a median maximum dose of 90 Gy and isodose line of 20%.
      Outcomes pertaining to pain and facial numbness were scored using Barrow
      Neurological Institute scales. RESULTS: Following a median latency period of 4
      weeks, we observed complete or adequate pain relief (Barrow Neurological
      Institute scores of I-IIIB) in 86 of 108 patients (90%). At a median time of 17
      months, 22 patients (26%) experienced pain recurrence. New-onset facial numbness
      was reported by 59 patients (55%). Treatment failure rates were highest among
      patients with a longer history of pain. Compared with patients with pain history
      of <=5 years, patients with pain history of >5 years experienced longer latency
      before pain relief (P = 0.027). Univariate and multivariate analyses demonstrated
      that pain history of <=5 years was a significant predictor of pain relief (P =
      0.049 and P = 0.045, respectively). CONCLUSIONS: GKRS achieves a high rate of
      pain relief among patients with medically refractory idiopathic TN. Pain history
      of <=5 years is a reliable predictor of pain relief and appears to be associated
      with shorter latency to pain relief after GKRS. Therefore, early GKRS for
      patients with medically refractory idiopathic TN is recommended.

PMID- 29371170
TI  - Comparison of Long-Term Fertility Outcomes after Myomectomy: Relationship with
      Number of Myomas Removed.
AB  - STUDY OBJECTIVE: To determine if the number of myomas removed during myomectomy
      for symptomatic relief affects long-term fertility outcomes in reproductive-aged
      women. DESIGN: Retrospective cohort survey study (Canadian Task Force
      classification II-2). SETTING: University hospital. PATIENTS: One hundred forty
      four patients who underwent myomectomy for symptomatic myomas and attempted to
      conceive afterward. INTERVENTION: Questionnaire mailed to reproductive-aged women
      who received robotic, laparoscopic, or abdominal myomectomy. MEASUREMENTS AND
      MAIN RESULTS: Patients with >6 myomas removed were less likely to achieve
      pregnancy after myomectomy than patients with <=6 myomas removed (22.9% vs 70.8%,
      respectively; p < .001). To achieve pregnancy, 45% of those with >6 myomas
      removed (vs 17.6% of those with <=6 myomas removed) relied on fertility treatment
      (clomiphene citrate, letrozole, intrauterine insemination, or in vitro
      fertilization). Of those with >6 myomas removed who became pregnant, 45.5% had a
      term birth, 45.5% miscarried, and 9.1% had an ectopic pregnancy. Of those with
      <=6 myomas removed who became pregnant, 61.8% had a term birth, 23.5% had a
      preterm birth, and 13.2% miscarried. CONCLUSION: The number of myomas removed
      during myomectomy significantly affects fertility. Women with >6 myomas removed
      were less likely to become pregnant, more likely to require fertility treatment,
      and less likely to have a term birth when compared with women with <=6 myomas
      removed.

PMID- 29371171
TI  - Simplified Laparoscopic Sacrohysteropexy.
AB  - STUDY OBJECTIVE: To demonstrate a simplified technique of performing laparoscopic
      sacrohysteropexy for uterine prolapse. DESIGN: A technical video demonstrating a
      simplified method of laparoscopic sacrohysteropexy (Canadian Task force
      classification level III). SETTING: The benign gynecology department at a
      university hospital. INTERVENTIONS: A 38-year old woman with grade 3 uterine
      descent presented requesting surgical management for symptomatic prolapse.
      CONCLUSION: Laparoscopic sacrohysteropexy is becoming an increasingly popular
      alternative to hysterectomy to treat uterine prolapse in women. We present a
      novel approach of performing laparoscopic sacrohysteropexy that differs from
      previously described methods [1,2]; it is shorter, simpler, and reduces possible
      complications. Key differences include the mesh type, site of attachment, and
      dissection of the peritoneum while creating the possibility of future vaginal
      delivery after pregnancy. Our simplified technique uses a polyvinylidene fluoride
      mesh woven with a square weave secured to the posterior aspect of the cervix
      under a layer of visceral peritoneum. Because there is no longitudinal give of
      the mesh, unlike polypropylene meshes with a diamond weave, a wrap method [2] is
      not required. No dissection of the broad ligament and bladder is needed,
      eliminating the risk of bladder perforation and anterior mesh erosion with fewer
      adhesions and simplifying hysterectomy if required in the future. We also
      uniquely "tunnel" the peritoneum, reducing the size of defect for suture closure,
      and reperitonize the mesh. Previous methods restrict cervical dilatation and
      require women to have cesarean sections. The method described in the video allows
      women to deliver vaginally and, in the event of late miscarriage, avoid the need
      for hysterotomy. We have performed 25 cases with 1 mild cystocoele recurrence
      requiring no surgery, 1 reoperation for posterior compartment repair, and 1 case
      of cervical elongation requiring Manchester repair. No cases of recurrent uterine
      prolapse have occurred.

PMID- 29371172
TI  - The Power Law of Learning in Transumbilical Single-Port Laparoscopic Subtotal
      Hysterectomy.
AB  - STUDY OBJECTIVE: To analyze the surgical outcomes and learning curve of
      transumbilical single-port laparoscopic subtotal hysterectomy, which requires
      sutures of the cervical stump. DESIGN: A prospective observational study
      (Canadian Task Force classification II-2). SETTING: A university-affiliated
      center. PATIENTS: From the first (July 2012) and consecutive patients of benign
      uterine disease scheduled for subtotal hysterectomy until October 2013.
      INTERVENTIONS: All single-port laparoscopies were performed using straight
      instruments by 1 gynecologist. An ancillary port was added whenever technical
      difficulties could endanger surgical quality. MEASUREMENT AND MAIN RESULTS:
      Seventy-five patients were recruited for intention-to-treat analysis with a mean
      (+/-SD) age of 44.7 +/- 3.8 years and a body mass index of 24.2 +/- 3.7 kg/m2. No
      major complication was noted. The mean uterine weight was 432.5 +/- 344.0 g with
      24 (32%) uteri ?500 g. The patients' sequential order, or gradually increasing
      experience, was the determining factor in progressively decreasing operative
      time. Furthermore, most cases that required an additional ancillary port (67%)
      were clustered in the first 20 cases, whereas 4 were scattered after the 47th
      patient because of severe pelvic adhesion. The mean operative time decreased in
      the power law function of the patients' sequential order with a plateau achieved
      at the 20th patient. CONCLUSION: The patients' sequential order was identified as
      an independent factor of achieving purely single-port access, and the trend of
      decreasing operative time delineated the existence of a learning curve.
      Approximately 20 patients were needed for an experienced multiport laparoscopist
      to reach technical competency in the current series.

PMID- 29371173
TI  - Temporary Simultaneous 2 Arterial Occlusions during Laparoscopic Management for
      Cornual Ectopic Pregnancy.
AB  - STUDY OBJECTIVE: To demonstrate a new technique of temporary simultaneous 2
      arterial occlusions (TESTOs) of the uterine and ovarian (or utero-ovarian) artery
      to reduce operative blood loss during laparoscopic cornual resection for cornual
      ectopic pregnancy. DESIGN: A step-by-step explanation of the surgical procedure
      using video (Canadian Task Force classification III). This study was approved by
      the institutional review board. SETTING: A university hospital. PATIENTS: A 41
      year-old woman presented with pelvic pain with 7 weeks of amenorrhea. A
      transvaginal sonogram and laboratory tests revealed left cornual pregnancy. She
      had a history of left salpingectomy caused by tubal pregnancy and wanted prompt
      surgical management without a surgical scar. INTERVENTIONS: During the single
      port laparoscopy, we found a 3-cm unruptured ectopic mass in the left uterine
      cornua. The retroperitoneum was opened using a harmonic scalpel (Ethicon
      Endosurgery, Cincinnati, OH) along the infundibulopelvic ligament. Then, both
      uterine arteries were temporarily occluded with a bulldog clamp (Aesculap,
      Tuttlingen, Germany) at the level where they originate from the internal iliac
      artery. The bulldog clamp, which is a spring-loaded crossover clamp with serrated
      blades that effectively occlude vessels without slippage or significant crush
      injury, is the laparoscopic instrument for minimizing blood loss during the
      surgical procedure. Each ovarian arterial vasculature was also transiently
      occluded at the utero-ovarian or ovarian pedicle by placing a bulldog clamp.
      Then, a uterine incision was made in the left cornua using a harmonic scalpel,
      the gestational conception was expressed through the incision, and corneal
      resection was completed. The uterine defect was closed using a V-Loc suture
      (Covidien, Mansfield, MA). In the final step, all vascular clamps were removed
      for reperfusion. MEASUREMENTS AND MAIN RESULTS: The operative time was 45
      minutes. The procedure time for TESTO and the occlusion time (defined as the time
      that the bilateral uterine and ovarian vessels were occluded by bulldog clamps)
      were 10 and 12 minutes, respectively. The estimated blood loss was 50 mL, and her
      postoperative hemoglobin was 11.9 g/dL from 13.0 g/dL preoperatively. No
      complications occurred in the postoperative course. Her menstruation resumed 2
      months after surgery. CONCLUSION: Surgical management of ectopic cornual
      pregnancy could be performed safely and efficiently under laparoscopy with the
      TESTO technique.

PMID- 29371174
TI  - Surgical Outcomes of Paravaginal Repair After Robotic Sacrocolpopexy.
AB  - STUDY OBJECTIVE: To evaluate surgical outcomes of robotic sacrocolpopexy with and
      without paravaginal repair for pelvic organ prolapse (POP). DESIGN: A
      retrospective cohort study with a 3-month postoperative follow-up (Canadian Task
      Force classification II-3). SETTING: An academic-affiliated community hospital
      with a practice comprised of 3 surgeons board certified in female pelvic medicine
      and reconstructive surgery. PATIENTS: Patients undergoing robotic sacrocolpopexy
      for POP from April 2013 through November 2014. INTERVENTIONS: Robotic paravaginal
      repair (RPVR) after robotic sacrocolpopexy. The decision to perform a paravaginal
      repair was at the discretion of the surgeon. MEASUREMENTS AND MAIN RESULTS: One
      hundred fifty-six patients underwent a robotic sacrocolpopexy. Twenty-four
      patients were excluded because of a lack of a 3-month postoperative follow-up.
      Nine patients underwent concomitant vaginal paravaginal repair and were also
      excluded. Outcomes were defined by comparing preoperative characteristics with
      those at the 3-month follow-up. Of the 123 patients in this cohort, 21 patients
      underwent a concomitant RPVR, and 102 did not. All Pelvic Organ Prolapse
      Questionnaire (POP-Q) points improved within groups (p < .001) except for the
      total vaginal length (TVL) in the RPVR group (p = .940). The Patient Global
      Impression of Improvement (PGI-I) did not differ between groups (1.2 vs 1.5, p =
      .128). Subgroup analysis was performed on patients with preoperative anterior
      wall prolapse of stage 3 or greater. Baseline characteristics and perioperative
      data were not remarkably different from the main cohort. All POP-Q points
      improved within groups (p < .001) except for the TVL in the RPVR group (p =
      .572). The PGI-I did not differ between groups (1.2 vs 1.3, p = .378).
      CONCLUSION: In both groups, anatomic markers substantially improved within each
      group. There were significant differences in postoperative POP-Q findings, which
      may have been influenced by the fact that patients undergoing RPVR usually had
      worse baseline prolapse. This selection bias creates difficulty with
      interpretation. Although in this study RPVR did not change subjective outcomes,
      further study is necessary to control for the severity of prolapse.

PMID- 29371175
TI  - Integrated Decentralized Training for Health Professions Education at the
      University of KwaZulu-Natal, South Africa: Protocol for the I-DecT Project.
AB  - BACKGROUND: The Integrated Decentralized Training (i-DecT) project was created to
      address the current need for health care in South Africa among resource poor
      climates in rural and periurban settings. The University of KwaZulu-Natal (UKZN)
      in South Africa has embarked on a program within the School of Health Sciences
      (SHS) to decentralize the clinical learning platform in order to address this
      disparity. Framed in a pragmatic stance, this proposal is geared towards
      informing the roll out of decentralized clinical training (DCT) within the
      province of KwaZulu-Natal. There currently remains uncertainty as to how the
      implementation of this program will unfold, especially for the diverse SHS, which
      includes specialities like audiology, dentistry, occupational therapy, optometry,
      pharmacy, physiotherapy, speech-language pathology, and sport science.
      Consequently, there is a need to carefully monitor and manage this DCT in order
      to ensure that the participating students have a positive learning experience and
      achieve expected academic outcomes, and that the needs of the communities are
      addressed adequately. OBJECTIVE: The study aims to explore the factors that will
      influence the roll-out of the DCT by developing an inclusive and context-specific
      model that will adhere to the standards set by the SHS for the DCT program at
      UKZN. METHODS: Key role players, including but not limited to, the South African
      Ministry of Health policy makers, clinicians, policy makers at UKZN, clinical
      educators, academicians, and students of UKZN within the SHS will participate in
      this project. Once the infrastructural, staffing and pedagogical enablers and
      challenges are identified, together with a review of existing models of
      decentralized training, a context-specific model for DCTl will be proposed based
      on initial pilot data that will be tested within iterative cycles in an Action
      Learning Action Research (ALAR) process. RESULTS: The study was designed to fit
      within the existing structures, and emerging framework and memorandum of
      understanding between the partners of this initiative, namely, the Ministry of
      Health and UKZN in order to develop health care professionals that are competent
      and prepared for the changing dynamics of healthcare in a developing world.
      CONCLUSIONS: It is envisioned that this study, the first to include a combination
      of health professionals in a DCT platform at UKZN, will not only contribute to
      effective service delivery, but may also serve to promote an interprofessional
      cooperation within the SHS and tertiary institutions in similar settings.

PMID- 29371176
TI  - Unhappy Patients Are Not Alike: Content Analysis of the Negative Comments from
      China's Good Doctor Website.
AB  - BACKGROUND: With the rise in popularity of Web 2.0 technologies, the sharing of
      patient experiences about physicians on online forums and medical websites has
      become a common practice. However, negative comments posted by patients are
      considered to be more influential by other patients and physicians than those
      that are satisfactory. OBJECTIVE: The aim of this study was to analyze negative
      comments posted online about physicians and to identify possible solutions to
      improve patient satisfaction, as well as their relationship with physicians.
      METHODS: A Java-based program was developed to collect patient comments on the
      Good Doctor website, one of the most popular online health communities in China.
      A total of 3012 negative comments concerning 1029 physicians (mean 2.93 [SD
      4.14]) from 5 highly ranked hospitals in Beijing were extracted for content
      analysis. An initial coding framework was constructed with 2 research assistants
      involved in the codification. RESULTS: Analysis, based on the collected 3012
      negative comments, revealed that unhappy patients are not alike and that their
      complaints cover a wide range of issues experienced throughout the whole process
      of medical consultation. Among them, physicians in Obstetrics and Gynecology
      (606/3012, 20.12%; P=.001) and Internal Medicine (487/3012, 16.17%; P=.80)
      received the most negative comments. For negative comments per physician,
      Dermatology and Sexually Transmitted Diseases (mean 5.72, P<.001) and Andrology
      (mean 5, P=.02) ranked the highest. Complaints relating to insufficient medical
      consultation duration (577/3012, 19.16%), physician impatience (527/3012,
      17.50%), and perceived poor therapeutic effect (370/3012, 12.28%) received the
      highest number of negative comments. Specific groups of people, such as those
      accompanying older patients or children, traveling patients, or very important
      person registrants, were shown to demonstrate little tolerance for poor medical
      service. CONCLUSIONS: Analysis of online patient complaints provides an
      innovative approach to understand factors associated with patient
      dissatisfaction. The outcomes of this study could be of benefit to hospitals or
      physicians seeking to improve their delivery of patient-centered services.
      Patients are expected to be more understanding of overloaded physicians'
      workloads, which are impacted by China's stretched medical resources, as efforts
      are made to build more harmonious physician-patient relationships.

PMID- 29371177
TI  - Evaluating Machine Learning-Based Automated Personalized Daily Step Goals
      Delivered Through a Mobile Phone App: Randomized Controlled Trial.
AB  - BACKGROUND: Growing evidence shows that fixed, nonpersonalized daily step goals
      can discourage individuals, resulting in unchanged or even reduced physical
      activity. OBJECTIVE: The aim of this randomized controlled trial (RCT) was to
      evaluate the efficacy of an automated mobile phone-based personalized and
      adaptive goal-setting intervention using machine learning as compared with an
      active control with steady daily step goals of 10,000. METHODS: In this 10-week
      RCT, 64 participants were recruited via email announcements and were required to
      attend an initial in-person session. The participants were randomized into either
      the intervention or active control group with a one-to-one ratio after a run-in
      period for data collection. A study-developed mobile phone app (which delivers
      daily step goals using push notifications and allows real-time physical activity
      monitoring) was installed on each participant's mobile phone, and participants
      were asked to keep their phone in a pocket throughout the entire day. Through the
      app, the intervention group received fully automated adaptively personalized
      daily step goals, and the control group received constant step goals of 10,000
      steps per day. Daily step count was objectively measured by the study-developed
      mobile phone app. RESULTS: The mean (SD) age of participants was 41.1 (11.3)
      years, and 83% (53/64) of participants were female. The baseline demographics
      between the 2 groups were similar (P>.05). Participants in the intervention group
      (n=34) had a decrease in mean (SD) daily step count of 390 (490) steps between
      run-in and 10 weeks, compared with a decrease of 1350 (420) steps among control
      participants (n=30; P=.03). The net difference in daily steps between the groups
      was 960 steps (95% CI 90-1830 steps). Both groups had a decrease in daily step
      count between run-in and 10 weeks because interventions were also provided during
      run-in and no natural baseline was collected. CONCLUSIONS: The results showed the
      short-term efficacy of this intervention, which should be formally evaluated in a
      full-scale RCT with a longer follow-up period. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT02886871; https://clinicaltrials.gov/ct2/show/NCT02886871
      (Archived by WebCite at http://www.webcitation.org/6wM1Be1Ng).

PMID- 29371178
TI  - Using Mobile Health Intervention to Improve Secondary Prevention of Coronary
      Heart Diseases in China: Mixed-Methods Feasibility Study.
AB  - BACKGROUND: Coronary heart disease (CHD) is the leading cause of cardiovascular
      mortality worldwide, yet implementation of evidence-based strategies for
      secondary prevention remains suboptimal. OBJECTIVE: This study aimed to evaluate
      the feasibility, specifically the usability and acceptability, and estimate the
      preliminary effectiveness of a mobile health (mHealth) intervention targeting
      both physicians and patients to improve adherence to evidence-based medications
      and lifestyle modifications. METHODS: We conducted a 12-week pre-post
      interventional pilot study at two sites in Shanghai and Hainan, China. Physicians
      used the app designed in this study to prescribe evidence-based medicines and
      record patient information. Eligible and consenting patients received automatic
      text messages or voice calls 4 to 5 times per week for 12 weeks on medication
      adherence and healthy behaviors. Interviews were conducted among 10 physicians
      and 24 patients at the two sites for their thoughts on medication adherence and
      feedback on the usability and acceptability. Questions on usability and
      acceptability were also asked in a patient follow-up survey. With regard to
      estimating effectiveness, the primary outcome was medication adherence (as
      estimated by the Morisky Green Levine Scale) at 12 weeks. Secondary outcomes
      included physical activity, smoking status, fruits and vegetables consumption,
      and facility visit frequency. RESULTS: Interview findings and patient survey
      showed the good usability and acceptability of the intervention. Among 190
      patients who completed the intervention, there was a significant increase in
      medication adherence (odds ratio [OR] 1.80, 95% CI 1.14-2.85). The study also
      showed decrease of smokers' percentage (-5%, P=.05), increase of daily vegetables
      consumption frequency (+0.3/day, P=.01), and community health care center visit
      frequency (+3 in 3 months, P=.04). The following site-specific differences were
      noted: medication adherence appeared to increase in Hainan (OR 14.68, 95% CI 5.20
      41.45) but not in Shanghai (OR 0.61, 95% CI 0.33-1.12). CONCLUSIONS: Our study
      demonstrated that the intervention was feasible in both a tertiary care center
      and an urban community health center in China. Preliminary results from pre-post
      comparison suggest the possibility that provider and patient-linked mHealth
      interventions may improve medication adherence and lifestyle modifications among
      CHD patients, especially in resource-scarce settings. Randomized controlled
      trials are needed to verify the findings.

PMID- 29371180
TI  - How Europe copes with flu.

PMID- 29371179
TI  - A rash that's more than skin deep.

PMID- 29371181
TI  - Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML
      stem cells.
AB  - Eradication of chemotherapy-resistant leukemia stem cells is expected to improve
      treatment outcomes in patients with acute myelogenous leukemia (AML). In a mouse
      model of AML expressing the MOZ-TIF2 fusion, we found that Ring1A and Ring1B,
      components of Polycomb repressive complex 1, play crucial roles in maintaining
      AML stem cells. Deletion of Ring1A and Ring1B (Ring1A/B) from MOZ-TIF2 AML cells
      diminished self-renewal capacity and induced the expression of numerous genes,
      including Glis2 Overexpression of Glis2 caused MOZ-TIF2 AML cells to
      differentiate into mature cells, whereas Glis2 knockdown in Ring1A/B-deficient
      MOZ-TIF2 cells inhibited differentiation. Thus, Ring1A/B regulate and maintain
      AML stem cells in part by repressing Glis2 expression, which promotes their
      differentiation. These findings provide new insights into the mechanism of AML
      stem cell homeostasis and reveal novel targets for cancer stem cell therapy.

PMID- 29371182
TI  - Failure of the private finance initiative.

PMID- 29371183
TI  - Hypertension guideline brings challenges, patient care opportunities.

PMID- 29371184
TI  - Study finds ED-based pharmacy personnel reduce drug-order error rates.

PMID- 29371185
TI  - Pharmacy students in Puerto Rico stay positive despite hardships.

PMID- 29371186
TI  - Robert D. Kerscher, founder of Lexi-Comp, dies at 69.

PMID- 29371187
TI  - Time to stop skyrocketing drug costs.

PMID- 29371188
TI  - Pharmacists in obstetrics.

PMID- 29371189
TI  - Improving the quality of patient experience through student engagement.

PMID- 29371190
TI  - Minimizing opioid use after acute major trauma.
AB  - PURPOSE: Results of an initiative at an academic medical center to reduce
      prescription opioid use in patients with acute traumatic injuries are reported.
      METHODS: In 2014, the University of Kentucky Hospital trauma service implemented
      a pain management strategy consisting of patient and provider education
      emphasizing the use of nonopioid analgesics to minimize opioid use without
      compromising analgesia effectiveness. To assess the impact of the initiative, a
      retrospective analysis of data on cohorts of patients admitted with acute trauma
      before (n = 489) and after (n = 424) project implementation was conducted. The
      primary endpoint was opioid use (prescribed daily milligram morphine equivalents
      [MME]) at discharge. Secondary endpoints included inpatient opioid and
      alternative analgesic use, pain control, ileus development, length of stay, and
      discharge disposition. RESULTS: Compared with the preintervention cohort, the
      postintervention cohort had a lower median daily discharge MME overall (45 MME
      versus 90 MME, p < 0.001); after stratification of MME data by baseline opioid
      use, this finding held true only for patients with no opioid prescription at
      admission. Although utilization of gabapentinoids, skeletal muscle relaxants, and
      clonidine increased during the postintervention period, inpatient opioid use did
      not differ significantly in the 2 cohorts. Utilization of both nonsteroidal
      antiinflammatory drugs and acetaminophen was lower in the postintervention cohort
      versus the preintervention cohort. CONCLUSION: Targeted provider and patient
      education on minimizing opioid use was associated with a reduction in MME on
      discharge from the hospital after traumatic injury.

PMID- 29371191
TI  - Development and validation of a transitions-of-care pharmacist tool to predict
      potentially avoidable 30-day readmissions.
AB  - PURPOSE: A practical tool for predicting the risk of 30-day readmissions using
      data readily available to pharmacists before hospital discharge is described.
      METHODS: A retrospective cohort study to identify predictors of potentially
      avoidable 30-day readmissions was conducted using transitions-of-care pharmacy
      notes and electronic medical record data from a large health system. Through
      univariate and multivariable logistic regression analyses of factors associated
      with unplanned readmissions in the study cohort (n = 690) over a 22-month period,
      a risk prediction tool was developed. The tool's discriminative ability was
      assessed using the C statistic; its calibration was assessed using the Hosmer
      Lemeshow goodness-of-fit test. RESULTS: Three factors predictive of readmission
      risk were identified; these variables-medication count, comobidity count, and
      health insurance status at discharge-form the 3-predictor MEDCOINS score. Among
      patients identified as being at high risk for readmission using the MEDCOINS
      tool, the estimated readmission risk was 22.5%, as compared with an observed
      readmission rate of 21.9%. The discriminatory performance of MEDCOINS scoring was
      fair (C statistic = 0.65 [95% confidence interval, 0.60-0.70]), with good
      calibration (Hosmer-Lemeshow p = 0.99). CONCLUSION: Among a cohort of patients
      who were seen by a transitions-of-care pharmacist during an inpatient
      hospitalization, comorbidity burden, number of medications, and health insurance
      coverage were most predictive of 30-day readmission. The MEDCOINS tool was found
      to have fair discriminative ability and good calibration.

PMID- 29371192
TI  - Novel approach to vancomycin level monitoring: Impact of a multidisciplinary
      monitoring system on timing of vancomycin levels.
AB  - PURPOSE: A novel approach to vancomycin level monitoring is described. METHODS:
      Vancomycin trough orders were added to the medication ordering system of a large
      teaching hospital and were generated when vancomycin was ordered. Pharmacists
      adjusted the order time so that the level was drawn appropriately. After
      pharmacist validation, the trough order appeared within the nursing medication
      list, and nurses were required to document when the level was drawn. Outcomes
      were evaluated before (retrospective group) and after (prospective group)
      implementation of this initiative. RESULTS: Among all patients for whom a
      vancomycin level was drawn, 24.0% of patients in the retrospective group had
      their first vancomycin level drawn within 2 hours of true trough, compared with
      87.2% of patients in the prospective group (p < 0.0001). Among all patients
      receiving vancomycin, significantly more patients in the prospective group had a
      level drawn within 2 hours of the true trough compared with the retrospective
      group (71.9% versus 20.6%, p < 0.0001). Further, significantly more patients in
      the prospective group had a vancomycin level ordered compared with the
      retrospective group (100.0% versus 90.8%, p < 0.0001). The mean +/- S.D. time
      from true trough that vancomycin levels were drawn was much longer in the
      retrospective group (184.9 +/- 84.8 minutes versus 58.3 +/- 60.7 minutes in the
      prospective group, p < 0.0001). CONCLUSION: A novel multidisciplinary approach to
      vancomycin trough monitoring involving automatic generation of trough orders,
      pharmacist validation of trough orders, and inclusion of trough orders in the
      nursing medication administration record was successful in significantly
      improving timing of vancomycin trough levels.

PMID- 29371193
TI  - Errors detected in pediatric oral liquid medication doses prepared in an
      automated workflow management system.
AB  - PURPOSE: The effectiveness of barcode-assisted medication preparation (BCMP)
      technology on detecting oral liquid dose preparation errors. METHODS: From June
      1, 2013, through May 31, 2014, a total of 178,344 oral doses were processed at
      Children's Mercy, a 301-bed pediatric hospital, through an automated workflow
      management system. Doses containing errors detected by the system's barcode
      scanning system or classified as rejected by the pharmacist were further
      reviewed. Errors intercepted by the barcode-scanning system were classified as
      (1) expired product, (2) incorrect drug, (3) incorrect concentration, and (4)
      technological error. Pharmacist-rejected doses were categorized into 6 categories
      based on the root cause of the preparation error: (1) expired product, (2)
      incorrect concentration, (3) incorrect drug, (4) incorrect volume, (5)
      preparation error, and (6) other. RESULTS: Of the 178,344 doses examined, 3,812
      (2.1%) errors were detected by either the barcode-assisted scanning system (1.8%,
      n = 3,291) or a pharmacist (0.3%, n = 521). The 3,291 errors prevented by the
      barcode-assisted system were classified most commonly as technological error and
      incorrect drug, followed by incorrect concentration and expired product. Errors
      detected by pharmacists were also analyzed. These 521 errors were most often
      classified as incorrect volume, preparation error, expired product, other,
      incorrect drug, and incorrect concentration. CONCLUSION: BCMP technology detected
      errors in 1.8% of pediatric oral liquid medication doses prepared in an automated
      workflow management system, with errors being most commonly attributed to
      technological problems or incorrect drugs. Pharmacists rejected an additional
      0.3% of studied doses.

PMID- 29371194
TI  - Development and implementation of a centralized comprehensive refill
      authorization program in an academic health system.
AB  - PURPOSE: The development and implementation of a centralized, comprehensive,
      refill authorization (CCRA) program within an academic health system are
      described. SUMMARY: In order to improve continuity of care for our medically
      complicated patients, ambulatory pharmacy services developed and implemented a
      highly coordinated CCRA program for multiple community clinics within the system.
      To implement the CCRA program, we centralized the refill-request intake process
      to the Pharmacy Ambulatory Clinical Care Center (PAC3). PAC3 technicians were
      incorporated into the refill authorization process, and the collaborative
      practice agreement was updated to standardize the pharmacist refill approval
      process at the PAC3. We successfully standardized and centralized the medication
      refill process from 10 community clinics with 95 family practice and internal
      medicine providers and 26 medical residents. We handled an average of 12,000
      refill requests each month, and pharmacists documented any interventions
      performed with each refill request. The cost savings associated with the CCRA
      program were attributed to the increased efficiency of the staff reviewing refill
      requests. The CCRA program increased the refill approval up to 10% compared with
      the previous decentralized refill authorization model. With the increased
      approval rate, the CCRA program saved 510 hours of our providers' time annually,
      which created time for an additional 1,530 clinic visits. We demonstrated a
      faster average turnaround time for refill authorization, from an average of 72
      hours before implementation to about 1 business day. CONCLUSION: Implementation
      of an integrated refill authorization service standardized the method by which
      patients' refill requests were addressed, increased refill efficiency, and
      improved refill authorization turnaround time.

PMID- 29371195
TI  - Clinical support role for a pharmacy technician within a primary care resource
      center.
AB  - PURPOSE: The creation of a clinical support role for a pharmacy technician within
      a primary care resource center is described. SUMMARY: In the Primary Care
      Resource Center (PCRC) Project, hospital-based care transition coordination hubs
      staffed by nurses and pharmacist teams were created in 6 independent community
      hospitals. At the largest site, patient volume for targeted diseases challenged
      the ability of the PCRC pharmacist to provide expected elements of care to
      targeted patients. Creation of a new pharmacy technician clinical support role
      was implemented as a cost-effective option to increase the pharmacist's
      efficiency. The pharmacist's work processes were reviewed and technical functions
      identified that could be assigned to a specially trained pharmacy technician
      under the direction of the PCRC pharmacist. Daily tasks performed by the pharmacy
      technician included maintenance of the patient roster and pending discharges,
      retrieval and documentation of pertinent laboratory and diagnostic test
      information from the patient's medical record, assembly of patient medication
      education materials, and identification of discrepancies between disparate
      systems' medication records. In the 6 months after establishing the PCRC pharmacy
      technician role, the pharmacist's completion of comprehensive medication reviews
      (CMRs) for target patients increased by 40.5% (p = 0.0223), driven largely by a
      42.4% (p < 0.0001) decrease in the time to complete each chart review.
      CONCLUSION: The addition of a pharmacy technician to augment pharmacist care in a
      PCRC team extended the reach of the pharmacist and allowed more time for the
      pharmacist to engage patients. Technician support enabled the pharmacist to
      complete more CMRs and reduced the time required for chart reviews.

PMID- 29371196
TI  - Hail to the radicals who founded ASHP.

PMID- 29371197
TI  - ASHP Award for Distinguished Leadership.

PMID- 29371198
TI  - ASHP/Association of Black Health-System Pharmacists Joint Leadership Award.

PMID- 29371199
TI  - Empathy and ethics: five minutes with Edzard Ernst.

PMID- 29371200
TI  - Lipid Testing and Statin Dosing After Acute Myocardial Infarction.
AB  - BACKGROUND: The 2013 American College of Cardiology/American Heart Association
      cholesterol guidelines recommend high-intensity statins for patients after
      myocardial infarction (MI) rather than treating to a low-density lipoprotein
      cholesterol goal, as the previous ATP III (Adult Treatment Panel third report)
      guidelines had advised. METHODS AND RESULTS: To evaluate the frequency of
      postdischarge lipid testing and high-intensity statin use among MI patients
      discharged on a statin during the ATP III guidelines era, we linked ACTION (Acute
      Coronary Treatment and Intervention Outcomes Network) Registry data to Medicare
      claims for 11 046 MI patients aged >=65 years who were discharged alive on a
      statin from 347 hospitals (2007-2009). Multivariable regression was used to
      evaluate the association between lipid testing and 1-year high-intensity statin
      use. Only 21% of MI patients were discharged on a high-intensity statin. By 90
      days after MI, 44% of patients discharged on a statin underwent lipid testing
      (43% on low- or moderate-intensity statins and 49% on high-intensity statins;
      P=0.001). Follow-up lipid testing rates were 47% among patients with in-hospital
      low-density lipoprotein cholesterol >=100 mg/dL and 47% among newly prescribed
      statin recipients. By 1 year, only 14% of patients were on high-intensity
      statins. Only 4% of patients discharged on low- or moderate-dose statin were
      uptitrated to high intensity; postdischarge lipid testing was associated with a
      slightly higher likelihood of high-intensity statin use by 1 year (5.4% versus
      2.9%, adjusted odds ratio: 1.92; 95% confidence interval, 1.52-2.41).
      CONCLUSIONS: Previous guidelines recommended low-density lipoprotein cholesterol
      goal-directed statin therapy, but lipid testing and high-intensity statin use
      were infrequent after MI. The American College of Cardiology/American Heart
      Association guidelines may promote more intensive cardiovascular risk reduction
      by eliminating treatment dependence on lipid testing.

PMID- 29371201
TI  - Nonmuscle Myosin Light Chain Kinase: A Key Player in Intermittent Hypoxia-Induced
      Vascular Alterations.
AB  - BACKGROUND: Obstructive sleep apnea is characterized by repetitive pharyngeal
      collapses during sleep, leading to intermittent hypoxia (IH), the main
      contributor of obstructive sleep apnea-related cardiovascular morbidity. In
      patients and rodents with obstructive sleep apnea exposed to IH, vascular
      inflammation and remodeling, endothelial dysfunction, and circulating
      inflammatory markers are linked with IH severity. The nonmuscle myosin light
      chain kinase (nmMLCK) isoform contributes to vascular inflammation and oxidative
      stress in different cardiovascular and inflammatory diseases. Thus, in the
      present study, we hypothesized that nmMLCK plays a key role in the IH-induced
      vascular dysfunctions and inflammatory remodeling. METHODS AND RESULTS: Twelve
      week-old nmMLCK+/+ or nmMLCK-/- mice were exposed to 14-day IH or normoxia. IH
      was associated with functional alterations characterized by an elevation of
      arterial blood pressure and stiffness and perturbations of NO signaling. IH
      caused endothelial barrier dysfunction (ie, reduced transendothelial resistance
      in vitro) and induced vascular oxidative stress associated with an inflammatory
      remodeling, characterized by an increased intima-media thickness and an increased
      expression and activity of inflammatory markers, such as interferon-gamma and
      nuclear factor-kappaB, in the vascular wall. Interestingly, nmMLCK deletion
      prevented all IH-induced functional and structural alterations, including the
      restoration of NO signaling, correction of endothelial barrier integrity, and
      reduction of both oxidative stress and associated inflammatory response.
      CONCLUSIONS: nmMLCK is a key mechanism in IH-induced vascular oxidative stress
      and inflammation and both functional and structural remodeling.

PMID- 29371202
TI  - Complement activation predicts adverse pregnancy outcome in patients with
      systemic lupus erythematosus and/or antiphospholipid antibodies.
AB  - OBJECTIVE: Studies in mouse models implicate complement activation as a causative
      factor in adverse pregnancy outcomes (APOs). We investigated whether activation
      of complement early in pregnancy predicts APOs in women with systemic lupus
      erythematosus (SLE) and/or antiphospholipid (aPL) antibodies. METHODS: The
      PROMISSE Study enrolled pregnant women with SLE and/or aPL antibodies (n=487) and
      pregnant healthy controls (n=204) at <12 weeks gestation and evaluated them
      monthly. APOs were: fetal/neonatal death, preterm delivery <36 weeks because of
      placental insufficiency or preeclampsia and/or growth restriction <5th
      percentile. Complement activation products were measured on serial blood samples
      obtained at each monthly visit. RESULTS: APO occurred in 20.5% of SLE and/or aPL
      pregnancies. As early as 12-15 weeks, levels of Bb and sC5b-9 were significantly
      higher in patients with APOs and remained elevated through 31 weeks compared with
      those with normal outcomes. Moreover, Bb and sC5b-9 were significantly higher in
      patients with SLE and/or aPL without APOs compared with healthy controls. In
      logistic regression analyses, Bb and sC5b-9 at 12-15 weeks remained significantly
      associated with APO (ORadj=1.41 per SD increase; 95% CI 1.06 to 1.89; P=0.019 and
      ORadj=1.37 per SD increase; 95% CI 1.05 to 1.80; P=0.022, respectively) after
      controlling for demographic and clinical risk factors for APOs in PROMISSE. When
      analyses were restricted to patients with aPL (n=161), associations between Bb at
      12-15 weeks and APOs became stronger (ORadj=2.01 per SD increase; 95% CI 1.16 to
      3.49; P=0.013). CONCLUSION: In pregnant patients with SLE and/or aPL, increased
      Bb and sC5b-9 detectable early in pregnancy are strongly predictive of APOs and
      support activation of complement, particularly the alternative pathway, as a
      contributor to APOs.

PMID- 29371204
TI  - Association between bisphosphonate use and risk of undergoing knee replacement in
      patients with osteoarthritis.

PMID- 29371203
TI  - Detection of myositis-specific antibodies.

PMID- 29371205
TI  - Health staff are more likely to question effectiveness of the flu vaccine.

PMID- 29371206
TI  - Peripheral T-cell lymphoma: novel backbone.

PMID- 29371207
TI  - TP53 mutations: the dawn of Shwachman clones.

PMID- 29371208
TI  - COOH-terminal SAA1 peptides fail to induce chemokines but synergize with CXCL8
      and CCL3 to recruit leukocytes via FPR2.
AB  - A natural leukocyte chemoattractant was isolated from bovine serum by an
      established 4-step purification procedure. Based on its relative molecular mass
      of 7287 and NH2-terminal sequence, the protein was identified as a carboxy
      terminal peptide of the acute phase protein serum amyloid A1 (SAA1). This SAA1(46
      112) fragment and its human equivalent SAA1(47-104) were chemically synthesized.
      Unlike intact SAA1alpha, these SAA fragments failed to directly chemoattract
      neutrophils and monocytes, to induce chemokines, and to stimulate downstream
      extracellular signal-regulated kinase signaling in monocytes. However, the SAA
      fragments potently synergized with CCL3 to induce monocyte migration and with
      CXCL8 to stimulate neutrophil shape changes and chemotaxis. Unlike intact
      SAA1alpha, SAA1(46-112) did not induce CXCL6 ex vivo but provoked a cooperative
      intraperitoneal neutrophil recruitment in mice when coinjected with CXCL6 into
      the peritoneal cavity. Moreover, SAA1(47-104) desensitized the synergy between
      intact SAA1alpha and CXCL8 in neutrophil chemotaxis, suggesting that this peptide
      binds formyl peptide receptor 2 (FPR2). This was evidenced by a complete blockade
      of synergy between the COOH-terminal SAA1 fragments and CXCL8 or CCL3 in
      neutrophil and monocyte chemotaxis, respectively, by the FPR2 antagonist WRW4
      Thus, SAA1 is degraded into fragments lacking chemokine-inducing capacity, while
      keeping synergy with cytokine-induced chemokines to sustain limited inflammation.

PMID- 29371209
TI  - A pernicious mean corpuscular volume.

PMID- 29371211
TI  - Research ethics for emerging trial designs: does equipoise need to adapt?

PMID- 29371212
TI  - Building an evidence base for the primary care workforce.

PMID- 29371213
TI  - Letter by Kuebler and Friedberg Regarding Article, "Pulmonary Artery Denervation
      by Determining Targeted Ablation Sites for Treatment of Pulmonary Arterial
      Hypertension".

PMID- 29371214
TI  - Response by Fujisawa et al to Letter Regarding Article, "Pulmonary Artery
      Denervation by Determining Targeted Ablation Sites for Treatment of Pulmonary
      Arterial Hypertension".

PMID- 29371215
TI  - Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in
      Pathological Remodeling.
AB  - BACKGROUND: Heart failure is a leading cause of mortality and morbidity, and the
      search for novel therapeutic approaches continues. In the monogenic disease
      mucopolysaccharidosis VI, loss-of-function mutations in arylsulfatase B lead to
      myocardial accumulation of chondroitin sulfate (CS) glycosaminoglycans,
      manifesting as myriad cardiac symptoms. Here, we studied changes in myocardial CS
      in nonmucopolysaccharidosis failing hearts and assessed its generic role in
      pathological cardiac remodeling. METHODS: Healthy and diseased human and rat left
      ventricles were subjected to histological and immunostaining methods to analyze
      glycosaminoglycan distribution. Glycosaminoglycans were extracted and analyzed
      for quantitative and compositional changes with Alcian blue assay and liquid
      chromatography-mass spectrometry. Expression changes in 20 CS-related genes were
      studied in 3 primary human cardiac cell types and THP-1-derived macrophages under
      each of 9 in vitro stimulatory conditions. In 2 rat models of pathological
      remodeling induced by transverse aortic constriction or isoprenaline infusion,
      recombinant human arylsulfatase B (rhASB), clinically used as enzyme replacement
      therapy in mucopolysaccharidosis VI, was administered intravenously for 7 or 5
      weeks, respectively. Cardiac function, myocardial fibrosis, and inflammation were
      assessed by echocardiography and histology. CS-interacting molecules were
      assessed with surface plasmon resonance, and a mechanism of action was verified
      in vitro. RESULTS: Failing human hearts displayed significant perivascular and
      interstitial CS accumulation, particularly in regions of intense fibrosis.
      Relative composition of CS disaccharides remained unchanged. Transforming growth
      factor-beta induced CS upregulation in cardiac fibroblasts. CS accumulation was
      also observed in both the pressure-overload and the isoprenaline models of
      pathological remodeling in rats. Early treatment with rhASB in the transverse
      aortic constriction model and delayed treatment in the isoprenaline model proved
      rhASB to be effective at preventing cardiac deterioration and augmenting
      functional recovery. Functional improvement was accompanied by reduced myocardial
      inflammation and overall fibrosis. Tumor necrosis factor-alpha was identified as
      a direct binding partner of CS glycosaminoglycan chains, and rhASB reduced tumor
      necrosis factor-alpha-induced inflammatory gene activation in vitro in
      endothelial cells and macrophages. CONCLUSIONS: CS glycosaminoglycans accumulate
      during cardiac pathological remodeling and mediate myocardial inflammation and
      fibrosis. rhASB targets CS effectively as a novel therapeutic approach for the
      treatment of heart failure.

PMID- 29371218
TI  - Fever in the returning traveller.

PMID- 29371216
TI  - Bmal1 in Perivascular Adipose Tissue Regulates Resting-Phase Blood Pressure
      Through Transcriptional Regulation of Angiotensinogen.
AB  - BACKGROUND: The perivascular adipose tissue (PVAT) surrounding vessels
      constitutes a distinct functional integral layer of the vasculature required to
      preserve vascular tone under physiological conditions. However, there is little
      information on the relationship between PVAT and blood pressure regulation,
      including its potential contributions to circadian blood pressure variation.
      METHODS: Using unique brown adipocyte-specific aryl hydrocarbon receptor nuclear
      translocator-like protein 1 (Bmal1) and angiotensinogen knockout mice, we
      determined the vasoactivity of homogenized PVAT in aortic rings and how brown
      adipocyte peripheral expression of Bmal1 and angiotensinogen in PVAT regulates
      the amplitude of diurnal change in blood pressure in mice. RESULTS: We uncovered
      a peripheral clock in PVAT and demonstrated that loss of Bmal1 in PVAT reduces
      blood pressure in mice during the resting phase, leading to a superdipper
      phenotype. PVAT extracts from wild-type mice significantly induced contractility
      of isolated aortic rings in vitro in an endothelium-independent manner. This
      property was impaired in PVAT from brown adipocyte-selective Bmal1-deficient (BA
      Bmal1-KO) mice. The PVAT contractile properties were mediated by local
      angiotensin II, operating through angiotensin II type 1 receptor-dependent
      signaling in the isolated vessels and linked to PVAT circadian regulation of
      angiotensinogen. Indeed, angiotensinogen mRNA and angiotensin II levels in PVAT
      of BA-Bmal1-KO mice were significantly reduced. Systemic infusion of angiotensin
      II, in turn, reduced Bmal1 expression in PVAT while eliminating the hypotensive
      phenotype during the resting phase in BA-Bmal1-KO mice. Angiotensinogen, highly
      expressed in PVAT, shows circadian expression in PVAT, and selective deletion of
      angiotensinogen in brown adipocytes recapitulates the phenotype of selective
      deletion of Bmal1 in brown adipocytes. Furthermore, angiotensinogen is a
      transcriptional target of Bmal1 in PVAT. CONCLUSIONS: These data indicate that
      local Bmal1 in PVAT regulates angiotensinogen expression and the ensuing increase
      in angiotensin II, which acts on smooth muscle cells in the vessel walls to
      regulate vasoactivity and blood pressure in a circadian fashion during the
      resting phase. These findings will contribute to a better understanding of the
      cardiovascular complications of circadian disorders, alterations in the circadian
      dipping phenotype, and cross-talk between systemic and peripheral regulation of
      blood pressure.

PMID- 29371217
TI  - Managing migraine in pregnancy.

PMID- 29371219
TI  - Gemin4 is an essential gene in mice, and its overexpression in human cells causes
      relocalization of the SMN complex to the nucleoplasm.
AB  - Gemin4 is a member of the Survival Motor Neuron (SMN) protein complex, which is
      responsible for the assembly and maturation of Sm-class small nuclear
      ribonucleoproteins (snRNPs). In metazoa, Sm snRNPs are assembled in the cytoplasm
      and subsequently imported into the nucleus. We previously showed that the SMN
      complex is required for snRNP import in vitro, although it remains unclear which
      specific components direct this process. Here, we report that Gemin4
      overexpression drives SMN and the other Gemin proteins from the cytoplasm into
      the nucleus. Moreover, it disrupts the subnuclear localization of the Cajal body
      marker protein, coilin, in a dose-dependent manner. We identified three putative
      nuclear localization signal (NLS) motifs within Gemin4, one of which is necessary
      and sufficient to direct nuclear import. Overexpression of Gemin4 constructs
      lacking this NLS sequestered Gemin3 and, to a lesser extent Gemin2, in the
      cytoplasm but had little effect on the nuclear accumulation of SMN. We also
      investigated the effects of Gemin4 depletion in the laboratory mouse, Mus
      musculusGemin4 null mice die early in embryonic development, demonstrating that
      Gemin4 is an essential mammalian protein. When crossed onto a severe SMA mutant
      background, heterozygous loss of Gemin4 failed to modify the early postnatal
      mortality phenotype of SMA type I (Smn-/-;SMN2+/+ ) mice. We conclude that Gemin4
      plays an essential role in mammalian snRNP biogenesis, and may facilitate import
      of the SMN complex (or subunits thereof) into the nucleus.

PMID- 29371220
TI  - Ethnic Differences in Prevalence of Post-stroke Depression.
AB  - BACKGROUND: Little is known about ethnic differences in poststroke depression
      (PSD) in the United States. This study aims to estimate the prevalence of PSD at
      90 days after first-ever stroke and to examine ethnic differences in the
      prevalence between Mexican Americans (MAs) and non-Hispanic whites (NHWs).
      METHODS AND RESULTS: Stroke cases from 2011 to 2015 were identified from the
      BASIC project (Brain Attack Surveillance in Corpus Christi)-a population-based
      stroke surveillance study in south Texas. Participants were interviewed at the
      onset of stroke (baseline interview) and ~90 days post-stroke (outcome
      interview). PSD was assessed by the Patient Health Questionnaire-8. Inverse
      probability weights were generated to account for differential attrition, and
      weighted logistic regression was used to investigate the association between
      ethnicity and PSD. The study sample consisted of 586 first-ever stroke patients
      who completed nonproxy baseline and outcome interviews and had depression
      assessment. Approximately, 60% of them were MAs, and 40% were NHWs. After
      accounting for attrition, the prevalence of depression at 90 days post-stroke was
      30.4% for MAs (95% confidence interval, 25.0%-35.9%) and 20.7% for NHWs (95%
      confidence interval, 15.7%-25.7%). The crude odds of PSD in MAs was 1.69 times
      greater than that in NHWs (95% confidence interval, 1.13-2.51). The odds ratio
      decreased by 23.6% after adjustment for education (odds ratio, 1.29; 95%
      confidence interval, 0.82-2.02) and was further attenuated with additional
      adjustment for other covariates. CONCLUSIONS: MAs had a higher prevalence of PSD
      at 90 days than NHWs. The ethnic difference was explained by sociodemographic and
      health factors, especially low educational attainment.

PMID- 29371221
TI  - Bringing Vioxx back to market.

PMID- 29371222
TI  - Programme frequency, type, time and duration do not explain the effects of
      balance exercise in older adults: a systematic review with a meta-regression
      analysis.
AB  - OBJECTIVE: The objective of this systematic review was to examine the effects of
      different balance exercise interventions compared with non-balance exercise
      controls on balance task performance in older adults. DESIGN: Systematic review.
      DATA SOURCES: Medline, Cumulative Index to Nursing and Allied Health Literature,
      EMBASE, Scopus and Cochrane Database of Systematic Reviews were searched until
      July 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and
      meta-analyses of randomised trials of balance exercise interventions for older
      adults were identified for extraction of eligible randomised trials. Eligibility
      criteria for inclusion of randomised trials in meta-analyses were comparison of a
      balance exercise intervention with a control group that did not perform balance
      exercises, report of at least one end-intervention balance outcome measurement
      that was consistent with the five subgroups of balance exercise identified, and
      full-text article available in English. RESULTS: Ninety-five trials were included
      in meta-analyses and 80 in meta-regressions. For four balance exercise types
      (control centre of mass, multidimensional, mobility and reaching), significant
      effects for balance exercise interventions were found in meta-analyses
      (standardised mean difference (SMD) 0.31-0.50), however with considerable
      heterogeneity in observed effects (I2: 50.4%-80.6%). Risk of bias assessments
      (Physiotherapy Evidence Database score and funnel plots) did not explain
      heterogeneity. One significant relationship identified in the meta-regressions of
      SMD and balance exercise frequency, time and duration explained 2.1% of variance
      for the control centre of mass subgroup. CONCLUSION: Limitations to this study
      included the variability in design of balance interventions, incomplete reporting
      of data and statistical heterogeneity. The design of balance exercise programmes
      provides inadequate explanation of the observed benefits of these interventions.

PMID- 29371223
TI  - Broad-spectrum physical fitness benefits of recreational football: a systematic
      review and meta-analysis.
AB  - BACKGROUND: A previous meta-analysis showed that maximal oxygen uptake increased
      by 3.51 mL/kg/min (95% CI 3.07 to 4.15) during a recreational football programme
      of 3-6 months in comparison with continuous moderate-intensity running, strength
      training or a passive control group. In addition, narrative reviews have
      demonstrated beneficial effects of recreational football on physical fitness and
      health status. OBJECTIVE: The purpose of this systematic review and meta-analysis
      was to evaluate the magnitude of effects of recreational football on blood
      pressure, body composition, lipid profile and muscular fitness with reference to
      age, gender and health status. DESIGN: Systematic review and meta-analysis. DATA
      SOURCES: MEDLINE, PubMed, SPORTDiscus, Web of Science, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL) and Google Scholar were searched
      prior to 1 February 2017. In addition, Google Scholar alerts were set up in
      January 2012 to identify potential papers with the following key terms:
      recreational football, recreational soccer, street football and street soccer.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised and matched controlled
      trials with participants allocated to a recreational football group or any other
      type of exercises or passive control group were included. Training programmes had
      to last at least 2 weeks to meet the inclusion criteria. The primary outcome
      measures were blood pressure, resting heart rate, body composition, muscular
      fitness, and blood lipids and glucose tolerance. A total of 31 papers met the
      inclusion criteria and were included. RESULTS: The effect of recreational
      football on systolic blood pressure (SBP) versus no-exercise controls was most
      likely extremely largely beneficial (effect size (ES)=4.20 mm Hg; 95% CI 1.87 to
      6.53). In addition, a most likely very large beneficial (ES=3.89 mm Hg; 95% CI
      2.33 to 5.44) effect was observed for diastolic blood pressure (DBP), when
      compared with non-active groups. Furthermore, a most likely extremely large
      beneficial effect was shown for SBP and DBP in participants with mild
      hypertension (11 and 7 mm Hg decrease, respectively) and participants with
      prehypertension (10 and 7 mm Hg decrease, respectively). Meta-analysis of
      recreational football determined the impact on resting heart rate as most likely
      extremely largely beneficial (ES=6.03 beats/min; 95% CI 4.43 to 7.64) when
      compared with non-active groups. The observed recreational football effect on fat
      mass was most likely largely beneficial (ES=1.72 kg; 95% CI 0.86 to 2.58) and the
      effect on countermovement jump (CMJ) performance was most likely very largely
      beneficial (ES=2.27 cm; 95% CI 1.29 to 3.25) when compared with non-active
      groups. Possibly beneficial decreases were found in low-density lipoprotein
      levels (ES=0.21 mmol/L; 95% CI 0.06 to 0.36). Possibly largely beneficial effect
      was observed for DBP in comparison with continuous running training. Small
      harmful and unclear results were noted for SBP, fat and lean body mass, body mass
      index, as well as muscular fitness when compared with running and Zumba training.
      CONCLUSION: The present meta-analysis demonstrated multiple broad-spectrum
      benefits of recreational football on health-related physical fitness compared
      with no-exercise controls, including improvements in blood pressure, resting
      heart rate, fat mass, low-density lipoprotein cholesterol and CMJ performance.
      Additionally, recreational football is efficient and effective as Zumba and
      continuous running exercise regimens with highlighted social, motivational and
      competitive components.

PMID- 29371224
TI  - Hip and groin pain in athletes: morphology, function and injury from a clinical
      perspective.

PMID- 29371225
TI  - Throw Like a Pro V.2.0 mobile app review.

PMID- 29371226
TI  - STINGing Antitumor Immunity into Action.
AB  - Efforts to stimulate STING signaling, thereby turning immunologically "cold"
      tumors "hot" and receptive to immunotherapy, are gaining ground in the industry.
      To date, directly targeting the STING receptor with synthetic ligands is the main
      approach to have entered clinical trials, but indirect small-molecule modulators
      of the pathway are also being pursued.

PMID- 29371227
TI  - Erratum for Pfaller et al., "In Vitro Activity of Delafloxacin against
      Contemporary Bacterial Pathogens from the United States and Europe, 2014".

PMID- 29371228
TI  - Erratum for Liu et al., "Plasmid-Mediated Novel blaNDM-17 Gene Encoding a
      Carbapenemase with Enhanced Activity in a Sequence Type 48 Escherichia coli
      Strain".

PMID- 29371229
TI  - Erratum for Dutta et al., "Metformin Adjunctive Therapy Does Not Improve the
      Sterilizing Activity of the First-Line Antitubercular Regimen in Mice".

PMID- 29371230
TI  - Rapid Uptake of the Subcutaneous Injectable in Burkina Faso: Evidence From
      PMA2020 Cross-Sectional Surveys.
AB  - The subcutaneous (SC) injectable, widely known by its commercial name Sayana
      Press, has potential to improve access to contraceptive methods. In Burkina Faso,
      SC-injectables were first piloted in select regions in 2014 and introduced
      nationally in 2016. PMA2020 is the first national survey to track programmatic
      progress of SC-injectable introduction at both population and health facility
      levels in the country across 2 rounds of data collection: March-May 2016 and
      November 2016-January 2017. Over this 6-month period, SC-injectable availability
      at public service delivery points increased from 50% to 85%, largely driven by
      increases in availability among the non-pilot regions. In terms of use, while the
      modern contraceptive prevalence rate among all women remained constant at about
      23%, SC-injectable prevalence nearly doubled from 1.1% to 2.0%, making up
      approximately 9% of all modern method users in Burkina Faso by late 2016, though
      the difference was not statistically significant. Increases were comparable
      between pilot and non-pilot regions. While the difference was not statistically
      significant, more rural women were using the method compared with their urban
      counterparts in the pilot regions, an interesting finding considering the
      opposite pattern is generally true for contraceptive prevalence nationally. In
      summary, following national scale-up, data show substantially improved
      availability of SC-injectables at service delivery points and potential for
      changes in the method mix in Burkina Faso. In order to further improve
      contraceptive access and choice, scale-up of community-based distribution of SC
      injectables should be considered, especially among rural populations with higher
      unmet need for family planning.

PMID- 29371231
TI  - A Q&A with the Qualcomm Tricorder XPRIZE Winners.

PMID- 29371233
TI  - Investigation into the Mechanism of Homo- and Heterodimerization of Angiotensin
      Converting Enzyme.
AB  - Angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin
      system (RAS), which is primarily responsible for blood pressure homeostasis.
      Studies have shown that ACE inhibitors yield cardiovascular benefits that cannot
      be entirely attributed to the inhibition of ACE catalytic activity. It is
      possible that these benefits are due to interactions between ACE and RAS
      receptors that mediate the protective arm of the RAS, such as angiotensin II
      receptor type 2 (AT2R) and the receptor MAS. Therefore, in this study, we
      investigated the molecular interactions of ACE, including ACE homodimerization
      and heterodimerization with AT2R and MAS, respectively. Molecular interactions
      were assessed by fluorescence resonance energy transfer and bimolecular
      fluorescence complementation in human embryonic kidney 293 cells and Chinese
      hamster ovary-K1 cells transfected with vectors encoding fluorophore-tagged
      proteins. The specificity of dimerization was verified by competition experiments
      using untagged proteins. These techniques were used to study several potential
      requirements for the germinal isoform of angiotensin-converting enzyme expressed
      in the testes (tACE) dimerization as well as the effect of ACE inhibitors on both
      somatic isoforms of angiotensin-converting enzyme expressed in the testes (sACE)
      and tACE dimerization. We demonstrated constitutive homodimerization of sACE and
      of both of its domains separately, as well as heterodimerization of both sACE and
      tACE with AT2R, but not MAS. In addition, we investigated both soluble sACE and
      the sACE N domain using size-exclusion chromatography-coupled small-angle X-ray
      scattering and we observed dimers in solution for both forms of the enzyme. Our
      results suggest that ACE homo- and heterodimerization does occur under
      physiologic conditions.

PMID- 29371232
TI  - MARCH1 protects the lipid raft and tetraspanin web from MHCII proteotoxicity in
      dendritic cells.
AB  - Dendritic cells (DCs) produce major histocompatibility complex II (MHCII) in
      large amounts to function as professional antigen presenting cells.
      Paradoxically, DCs also ubiquitinate and degrade MHCII in a constitutive manner.
      Mice deficient in the MHCII-ubiquitinating enzyme membrane-anchored RING-CH1, or
      the ubiquitin-acceptor lysine of MHCII, exhibit a substantial reduction in the
      number of regulatory T (Treg) cells, but the underlying mechanism was unclear.
      Here we report that ubiquitin-dependent MHCII turnover is critical to maintain
      homeostasis of lipid rafts and the tetraspanin web in DCs. Lack of MHCII
      ubiquitination results in the accumulation of excessive quantities of MHCII in
      the plasma membrane, and the resulting disruption to lipid rafts and the
      tetraspanin web leads to significant impairment in the ability of DCs to engage
      and activate thymocytes for Treg cell differentiation. Thus, ubiquitin-dependent
      MHCII turnover represents a novel quality-control mechanism by which DCs maintain
      homeostasis of membrane domains that support DC's Treg cell-selecting function.

PMID- 29371235
TI  - SRT2104 attenuates diabetes-induced aortic endothelial dysfunction via inhibition
      of P53.
AB  - Endothelial dysfunction contributes to diabetic macrovascular complications.
      Sirtuin 1 (SIRT1) protects against diabetic vasculopathy. SRT2104 is a novel
      SIRT1 activator and was not previously studied for its effects on diabetes
      induced aortic endothelial dysfunction. Additionally, whether or to what extent
      deacetylation of P53, a substrate of SIRT1, is required for the effects of SIRT1
      activation was unclear, given the fact that SIRT1 has multiple targets. Moreover,
      little was known about the pathogenic role of P53 in diabetes-induced aortic
      injury. To these ends, diabetes was induced by streptozotocin in C57BL/6 mice.
      The diabetic mice developed enhanced aortic contractility, oxidative stress,
      inflammation, P53 hyperacetylation and a remarkable decrease in SIRT1 protein,
      the effects of which were rescued by SRT2104. In HG-treated endothelial cells
      (ECs), P53 siRNA and SRT2104 produced similar effects on the induction of SIRT1
      and the inhibition of P53 acetylation, oxidative stress and inflammation.
      Interestingly, SRT2104 failed to further enhance these effects in the presence of
      P53 siRNA. Moreover, P53 activation by nutlin3a completely abolished SRT2104's
      protection against HG-induced oxidative stress and inflammation. Further, forced
      activation of P53 by nutlin3a increased aortic contractility in the healthy mice
      and generated endothelial oxidative stress and inflammation in both the normal
      glucose-cultured ECs and the aortas of the healthy mice. Collectively, the
      present study demonstrates that P53 deacetylation predominantly mediates
      SRT2104's protection against diabetes-induced aortic endothelial dysfunction and
      highlights the pathogenic role of P53 in aortic endothelial dysfunction.

PMID- 29371234
TI  - Disordered Eating Behaviors Are Not Increased by an Intervention to Improve Diet
      Quality but Are Associated With Poorer Glycemic Control Among Youth With Type 1
      Diabetes.
AB  - OBJECTIVE: This study examines whether participation in an 18-month behavioral
      intervention shown previously to improve overall diet quality inadvertently
      increases disordered eating behaviors (DEBs) in youth with type 1 diabetes and
      investigates the association of DEB with multiple measures of glycemic control
      and variability. RESEARCH DESIGN AND METHODS: Participants reported DEB and
      diabetes management at baseline and 6, 12, and 18 months; masked continuous
      glucose monitoring, HbA1c, and 1,5-anhydroglucitol (1,5-AG) were obtained
      concurrently. Linear mixed models estimated the intervention effect on DEB, the
      association of DEB with diabetes adherence and measures of glycemic control and
      variability, and whether DEB modified glycemic trajectories. RESULTS: There was
      no intervention effect on DEB (P = 0.84). DEB was associated with higher HbA1c (P
      = 0.001), mean sensor glucose (P = 0.001), and percent sensor glucose values >180
      mg/dL (P = <0.001); with lower 1,5-AG (P = 0.01); and with worse diabetes
      adherence (P = 0.03). DEB was not associated with percent sensor glucose values
      <70 mg/dL or any measures of glycemic variability. There was a significant DEB *
      time interaction effect for mean sensor glucose (P = 0.05) and percent sensor
      glucose values >180 mg/dL (P = 0.04). Participants reporting less DEB had a
      developmentally expected deterioration in glycemic control throughout the study.
      Participants reporting more DEB had poor glycemic control at baseline that
      remained poor throughout the study. CONCLUSIONS: Findings show a potential to
      improve diet quality without increasing DEB and indicate an association of DEB
      with persistent hyperglycemia but not hypoglycemia or glycemic variability.

PMID- 29371236
TI  - CRABP1 protects the heart from isoproterenol-induced acute and chronic
      remodeling.
AB  - Excessive and/or persistent activation of calcium-calmodulin protein kinase II
      (CaMKII) is detrimental in acute and chronic cardiac injury. However, intrinsic
      regulators of CaMKII activity are poorly understood. We find that cellular
      retinoic acid-binding protein 1 (CRABP1) directly interacts with CaMKII and
      uncover a functional role for CRABP1 in regulating CaMKII activation. We
      generated Crabp1-null mice (CKO) in C57BL/6J background for pathophysiological
      studies. CKO mice develop hypertrophy as adults, exhibiting significant left
      ventricular dilation with reduced ejection fraction at the baseline cardiac
      function. Interestingly, CKO mice have elevated basal CaMKII phosphorylation at
      T287, and phosphorylation on its substrate phospholamban (PLN) at T17. Acute
      isoproterenol (ISO) challenge (80 mg/kg two doses in 1 day) causes more severe
      apoptosis and necrosis in CKO hearts, and treatment with a CaMKII inhibitor KN-93
      protects CKO mice from this injury. Chronic (30 mg/kg/day) ISO challenge also
      significantly increases hypertrophy and fibrosis in CKO mice as compared to WT.
      In wild-type mice, CRABP1 expression is increased in early stages of ISO
      challenge and eventually reduces to the basal level. Mechanistically, CRABP1
      directly inhibits CaMKII by competing with calmodulin (CaM) for CaMKII
      interaction. This study demonstrates increased susceptibility of CKO mice to ISO
      induced acute and chronic cardiac injury due to, at least in part, elevated
      CaMKII activity. Deleting Crabp1 results in reduced baseline cardiac function and
      aggravated damage challenged with acute and persistent beta-adrenergic
      stimulation. This is the first report of a physiological role of CRABP1 as an
      endogenous regulator of CaMKII, which protects the heart from ISO-induced damage.

PMID- 29371238
TI  - Potential Opportunities for Prevention or Earlier Diagnosis of Child Physical
      Abuse in the Inpatient Setting.
AB  - OBJECTIVES: To compare rates of previous inpatient visits among children
      hospitalized with child physical abuse (CPA) with controls as well as between
      individual abuse types. METHODS: In this study, we used the Pediatric Health
      Information System administrative database of 44 children's hospitals. Children
      <6 years of age hospitalized with CPA between January 1, 2011, and September 30,
      2015, were identified by discharge codes and propensity matched to accidental
      injury controls. Rates for previous visit types were calculated per 10 000 months
      of life. chi2 and Poisson regression were used to compare proportions and rates.
      RESULTS: There were 5425 children hospitalized for CPA. Of abuse and accident
      cases, 13.1% and 13.2% had a previous inpatient visit, respectively. At previous
      visits, abused children had higher rates of fractures (rate ratio [RR] = 3.0
      times; P = .018), head injuries (RR = 3.5 times; P = .005), symptoms concerning
      for occult abusive head trauma (AHT) (eg, isolated vomiting, seizures, brief
      resolved unexplained events) (RR = 1.4 times; P = .054), and perinatal conditions
      (eg, prematurity) (RR = 1.3 times; P = .014) compared with controls. Head
      injuries and symptoms concerning for occult AHT also more frequently preceded
      cases of AHT compared with other types of abuse (both P < .001). CONCLUSIONS:
      Infants hospitalized with perinatal-related conditions, symptoms concerning for
      occult AHT, and injuries are inpatient populations who may benefit from abuse
      prevention efforts and/or risk assessments. Head injuries and symptoms concerning
      for occult AHT (eg, isolated vomiting, seizures, and brief resolved unexplained
      events) may represent missed opportunities to diagnose AHT in the inpatient
      setting; however, this requires further study.

PMID- 29371237
TI  - Cell-specific responses to the cytokine TGFbeta are determined by variability in
      protein levels.
AB  - The cytokine TGFbeta provides important information during embryonic development,
      adult tissue homeostasis, and regeneration. Alterations in the cellular response
      to TGFbeta are involved in severe human diseases. To understand how cells encode
      the extracellular input and transmit its information to elicit appropriate
      responses, we acquired quantitative time-resolved measurements of pathway
      activation at the single-cell level. We established dynamic time warping to
      quantitatively compare signaling dynamics of thousands of individual cells and
      described heterogeneous single-cell responses by mathematical modeling. Our
      combined experimental and theoretical study revealed that the response to a given
      dose of TGFbeta is determined cell specifically by the levels of defined
      signaling proteins. This heterogeneity in signaling protein expression leads to
      decomposition of cells into classes with qualitatively distinct signaling
      dynamics and phenotypic outcome. Negative feedback regulators promote
      heterogeneous signaling, as a SMAD7 knock-out specifically affected the signal
      duration in a subpopulation of cells. Taken together, we propose a quantitative
      framework that allows predicting and testing sources of cellular signaling
      heterogeneity.

PMID- 29371240
TI  - You Can't Treat a Problem if You Don't Recognize It.

PMID- 29371239
TI  - Catheter sepsis and antisepsis: matters of life, death, obscurity and resistance.

PMID- 29371241
TI  - Clinical Decision Support for Recognition and Management of Hypertension: A
      Randomized Trial.
AB  - OBJECTIVES: Although blood pressure (BP) is routinely measured in outpatient
      visits, elevated BP and hypertension are often not recognized. We evaluated
      whether an electronic health record-linked clinical decision support (CDS) tool
      could improve the recognition and management of hypertension in adolescents.
      METHODS: We randomly assigned 20 primary care clinics within an integrated care
      system to CDS or usual care. At intervention sites, the CDS displayed BPs and
      percentiles, identified incident hypertension on the basis of current or previous
      BPs, and offered tailored order sets. The recognition of hypertension was
      identified by an automated review of diagnoses and problem lists and a manual
      review of clinical notes, antihypertensive medication prescriptions, and
      diagnostic testing. Generalized linear mixed models were used to test the effect
      of the intervention. RESULTS: Among 31 579 patients 10 to 17 years old with a
      clinic visit over a 2-year period, 522 (1.7%) had incident hypertension. Within 6
      months of meeting criteria, providers recognized hypertension in 54.9% of
      patients in CDS clinics and 21.3% of patients in usual care (P <= .001). Clinical
      recognition was most often achieved through visit diagnoses or documentation in
      the clinical note. Within 6 months of developing incident hypertension, 17.1% of
      CDS subjects were referred to dieticians or weight loss or exercise programs, and
      9.4% had additional hypertension workup versus 3.9% and 4.2%, respectively (P =
      .001 and .046, respectively). Only 1% of patients were prescribed an
      antihypertensive medication within 6 months of developing hypertension.
      CONCLUSIONS: The CDS had a significant, beneficial effect on the recognition of
      hypertension, with a moderate increase in guideline-adherent management.

PMID- 29371242
TI  - Plasminogen Activator Inhibitor-1 Promotes Neutrophil Infiltration and Tissue
      Injury on Ischemia-Reperfusion.
AB  - OBJECTIVE: Ischemia-reperfusion (I/R) injury significantly contributes to organ
      dysfunction and failure after myocardial infarction, stroke, and transplantation.
      In addition to its established role in the fibrinolytic system, plasminogen
      activator inhibitor-1 has recently been implicated in the pathogenesis of I/R
      injury. The underlying mechanisms remain largely obscure. APPROACH AND RESULTS:
      Using different in vivo microscopy techniques as well as ex vivo analyses and in
      vitro assays, we identified that plasminogen activator inhibitor-1 rapidly
      accumulates on microvascular endothelial cells on I/R enabling this protease
      inhibitor to exhibit previously unrecognized functional properties by inducing an
      increase in the affinity of beta2 integrins in intravascularly rolling
      neutrophils. These events are mediated through low-density lipoprotein receptor
      related protein-1 and mitogen-activated protein kinase-dependent signaling
      pathways that initiate intravascular adherence of these immune cells to the
      microvascular endothelium. Subsequent to this process, extravasating neutrophils
      disrupt endothelial junctions and promote the postischemic microvascular leakage.
      Conversely, deficiency of plasminogen activator inhibitor-1 effectively reversed
      leukocyte infiltration, microvascular dysfunction, and tissue injury on
      experimental I/R without exhibiting side effects on microvascular hemostasis.
      CONCLUSIONS: Our experimental data provide novel insights into the
      nonfibrinolytic properties of the fibrinolytic system and emphasize plasminogen
      activator inhibitor-1 as a promising target for the prevention and treatment of
      I/R injury.

PMID- 29371243
TI  - Lipoprotein Lipase Deficiency Impairs Bone Marrow Myelopoiesis and Reduces
      Circulating Monocyte Levels.
AB  - OBJECTIVE: Tissue macrophages induce and perpetuate proinflammatory responses,
      thereby promoting metabolic and cardiovascular disease. Lipoprotein lipase (LpL),
      the rate-limiting enzyme in blood triglyceride catabolism, is expressed by
      macrophages in atherosclerotic plaques. We questioned whether LpL, which is also
      expressed in the bone marrow (BM), affects circulating white blood cells and BM
      proliferation and modulates macrophage retention within the artery. APPROACH AND
      RESULTS: We characterized blood and tissue leukocytes and inflammatory molecules
      in transgenic LpL knockout mice rescued from lethal hypertriglyceridemia within
      18 hours of life by muscle-specific LpL expression (MCKL0 mice). LpL-deficient
      mice had ~40% reduction in blood white blood cell, neutrophils, and total and
      inflammatory monocytes (Ly6C/Ghi). LpL deficiency also significantly decreased
      expression of BM macrophage-associated markers (F4/80 and TNF-alpha [tumor
      necrosis factor alpha]), master transcription factors (PU.1 and C/EBPalpha), and
      colony-stimulating factors (CSFs) and their receptors, which are required for
      monocyte and monocyte precursor proliferation and differentiation. As a result,
      differentiation of macrophages from BM-derived monocyte progenitors and monocytes
      was decreased in MCKL0 mice. Furthermore, although LpL deficiency was associated
      with reduced BM uptake and accumulation of triglyceride-rich particles and
      macrophage CSF-macrophage CSF receptor binding, triglyceride lipolysis products
      (eg, linoleic acid) stimulated expression of macrophage CSF and macrophage CSF
      receptor in BM-derived macrophage precursor cells. Arterial macrophage numbers
      decreased after heparin-mediated LpL cell dissociation and by genetic knockout of
      arterial LpL. Reconstitution of LpL-expressing BM replenished aortic macrophage
      density. CONCLUSIONS: LpL regulates peripheral leukocyte levels and affects BM
      monocyte progenitor differentiation and aortic macrophage accumulation.

PMID- 29371244
TI  - Cell Type-Specific Contributions of the Angiotensin II Type 1a Receptor to Aorta
      Homeostasis and Aneurysmal Disease-Brief Report.
AB  - OBJECTIVE: Two were the aims of this study: first, to translate whole-genome
      expression profiles into computational predictions of functional associations
      between signaling pathways that regulate aorta homeostasis and the activity of
      angiotensin II type 1a receptor (At1ar) in either vascular endothelial or smooth
      muscle cells; and second, to characterize the impact of endothelial cell- or
      smooth muscle cell-specific At1ar disruption on the development of thoracic
      aortic aneurysm in fibrillin-1 hypomorphic (Fbn1mgR/mgR ) mice, a validated
      animal model of early onset progressively severe Marfan syndrome. APPROACH AND
      RESULTS: Cdh5-Cre and Sm22-Cre transgenic mice were used to inactivate the At1ar
      coding gene (Agt1ar) in either intimal or medial cells of both wild type and
      Marfan syndrome mice, respectively. Computational analyses of differentially
      expressed genes predicted dysregulated signaling pathways of cell survival and
      matrix remodeling in Agt1arCdh5-/- aortas and of cell adhesion and contractility
      in Agt1arSm22-/- aortas. Characterization of Fbn1mgR/mgR;Agt1arCdh5-/- mice
      revealed increased median survival associated with mitigated aneurysm growth and
      media degeneration, as well as reduced levels of phosphorylated (p-) Erk1/2 but
      not p-Smad2. By contrast, levels of both p-Erk1/2 and p-Smad2 proteins were
      normalized in Fbn1mgR/mgR;Agt1arSm22-/- aortas in spite of them showing no
      appreciable changes in thoracic aortic aneurysm pathology. CONCLUSIONS:
      Physiological At1ar signaling in the intimal and medial layers is associated with
      distinct regulatory processes of aorta homeostasis and function; improper At1ar
      activity in the vascular endothelium is a significant determinant of thoracic
      aortic aneurysm development in Marfan syndrome mice.

PMID- 29371245
TI  - Prevalence of Calcification in Human Femoropopliteal Arteries and its Association
      with Demographics, Risk Factors, and Arterial Stiffness.
AB  - OBJECTIVE: Arterial calcification and stiffening increase the risk of
      reconstruction failure, amputation, and mortality in patients with peripheral
      arterial disease, but underlying mechanisms and prevalence are unclear. APPROACH
      AND RESULTS: Fresh human femoropopliteal arteries were obtained from n=431 tissue
      donors aged 13 to 82 years (mean age, 53+/-16 years) recording the in situ
      longitudinal prestretch. Arterial diameter, wall thickness, and opening angles
      were measured optically, and stiffness was assessed using planar biaxial
      extension and constitutive modeling. Histological features were determined using
      transverse and longitudinal Verhoeff-Van Gieson and Alizarin stains. Medial
      calcification was quantified using a 7-stage grading scale and was correlated
      with structural and mechanical properties and clinical characteristics. Almost
      half (46%) of the femoropopliteal arteries had identifiable medial calcification.
      Older arteries were more calcified, but small calcium deposits were observed in
      arteries as young as 18 years old. After controlling for age, positive
      correlations were observed between calcification, diabetes mellitus,
      dyslipidemia, and body mass index. Tobacco use demonstrated a negative
      correlation. Calcified arteries were larger in diameter but had smaller
      circumferential opening angles. They were also stiffer longitudinally and
      circumferentially and had thinner tunica media and external elastic lamina with
      more discontinuous elastic fibers. CONCLUSIONS: Although aging is the dominant
      risk factor for femoropopliteal artery calcification and stiffening, these
      processes seem to be linked and can begin at a young age. Calcification is
      associated with the presence of certain risk factors and with elastic fiber
      degradation, suggesting overlapping molecular pathways that require further
      investigation.

PMID- 29371246
TI  - MTHFR Gene and Serum Folate Interaction on Serum Homocysteine Lowering: Prospect
      for Precision Folic Acid Treatment.
AB  - OBJECTIVE: This post hoc analysis of the CSPPT (China Stroke Primary Prevention
      Trial) assessed the individual variation in total homocysteine (tHcy)-lowering
      response after an average 4.5 years of 0.8 mg daily folic acid therapy in Chinese
      hypertensive adults and evaluated effect modification by
      methylenetetrahydrofolate reductase (MTHFR) C677T genotypes and serum folate
      levels. APPROACH AND RESULTS: This analysis included 16 413 participants from the
      CSPPT, who were randomly assigned to 2 double-blind treatment groups: either 10
      mg enalapril+0.8-mg folic acid or 10-mg enalapril, daily and had individual
      measurements of serum folate and tHcy levels at baseline and exit visits and
      MTHFR C677T genotypes. Mean baseline tHcy levels were comparable between the 2
      treatment groups (14.5+/-8.5 versus 14.4+/-8.1 MUmol/L; P=0.561). After 4.5 years
      of treatment, mean tHcy levels were reduced to 12.7+/-6.1 MUmol/L in the
      enalapril+folic acid group, but almost stayed the same in the enalapril group
      (14.4+/-7.9 MUmol/L, group difference: 1.61 MUmol/L; 11% reduction). More
      importantly, tHcy lowering varied by MTHFR genotypes and serum folate levels.
      Compared with CC and CT genotypes, participants with the TT genotype had a more
      prominent L-shaped curve between tHcy and serum folate levels and required higher
      folate levels (at least 15 ng/mL) to eliminate the differences in tHcy by
      genotypes. CONCLUSIONS: Compared with CC or CT, tHcy in the TT group manifested a
      heightened L-shaped curve from low to high folate levels, but this difference in
      tHcy by genotype was eliminated when plasma folate levels reach ~15 ng/mL or
      higher. Our data raised the prospect to tailor folic acid therapy according to
      individual MTHFR C677T genotype and folate status. CLINICAL TRIAL REGISTRATION:
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

PMID- 29371247
TI  - IL-35 (Interleukin-35) Suppresses Endothelial Cell Activation by Inhibiting
      Mitochondrial Reactive Oxygen Species-Mediated Site-Specific Acetylation of H3K14
      (Histone 3 Lysine 14).
AB  - OBJECTIVE: IL-35 (interleukin-35) is an anti-inflammatory cytokine, which
      inhibits immune responses by inducing regulatory T cells and regulatory B cells
      and suppressing effector T cells and macrophages. It remains unknown whether
      atherogenic stimuli induce IL-35 and whether IL-35 inhibits atherogenic lipid
      induced endothelial cell (EC) activation and atherosclerosis. EC activation
      induced by hyperlipidemia stimuli, including lysophosphatidylcholine is
      considered as an initiation step for monocyte recruitment and atherosclerosis. In
      this study, we examined the expression of IL-35 during early atherosclerosis and
      the roles and mechanisms of IL-35 in suppressing lysophosphatidylcholine-induced
      EC activation. APPROACH AND RESULTS: Using microarray and ELISA, we found that IL
      35 and its receptor are significantly induced during early atherosclerosis in the
      aortas and plasma of ApoE (apolipoprotein E) knockout mice-an atherosclerotic
      mouse model-and in the plasma of hypercholesterolemic patients. In addition, we
      found that IL-35 suppresses lysophosphatidylcholine-induced monocyte adhesion to
      human aortic ECs. Furthermore, our RNA-sequencing analysis shows that IL-35
      selectively inhibits lysophosphatidylcholine-induced EC activation-related genes,
      such as ICAM-1 (intercellular adhesion molecule-1). Mechanistically, using flow
      cytometry, mass spectrometry, electron spin resonance analyses, and chromatin
      immunoprecipitation-sequencing analyses, we found that IL-35 blocks
      lysophosphatidylcholine-induced mitochondrial reactive oxygen species, which are
      required for the induction of site-specific H3K14 (histone 3 lysine 14)
      acetylation, increased binding of proinflammatory transcription factor AP-1 in
      the promoter of ICAM-1, and induction of ICAM-1 transcription in human aortic EC.
      Finally, IL-35 cytokine therapy suppresses atherosclerotic lesion development in
      ApoE knockout mice. CONCLUSIONS: IL-35 is induced during atherosclerosis
      development and inhibits mitochondrial reactive oxygen species-H3K14 acetylation
      AP-1-mediated EC activation.

PMID- 29371248
TI  - From High-Density Lipoprotein Cholesterol to Measurements of Function: Prospects
      for the Development of Tests for High-Density Lipoprotein Functionality in
      Cardiovascular Disease.
AB  - The evidence is strong that biological functions contained in high-density
      lipoproteins (HDL) are antiatherogenic. These functions may track with HDL
      cholesterol or apolipoprotein A1 concentration to explain the strongly inverse
      risk curve for cardiovascular disease. Moreover, there are harmful as well as
      protective HDL subspecies in regard to cardiovascular disease, which could be
      responsible for paradoxical responses to HDL-directed treatments. Recent
      metabolic studies show that apolipoprotein A1-containing HDL is secreted into the
      circulation as mostly spherical cholesterol ester-rich lipoproteins that span the
      HDL size range. Most of the flux of apolipoprotein A1 HDL into and out of the
      circulation occurs in these spherical cholesterol-replete particles. Discoidal
      cholesterol-poor HDL comprises a minority of HDL secretion. We propose that much
      cholesterol in reverse cholesterol transport enters and exits medium and large
      size HDL without changing a size category, and its flux may be estimated
      provisionally from holoparticle clearance of cholesterol ester-rich HDL. An
      accurate framework for metabolism of HDL is essential to finding steady-state
      biomarkers that reflect HDL function in vivo. Whereas cholesterol efflux from
      cells to mainly discoidal HDL, mediated by ABCA1 (ATP-binding cassette
      transporter ABCA1), predicts cardiovascular disease, cholesterol transfers to
      spherical HDL also can be measured and may be relevant to protection against
      atherosclerosis. We propose several investigative paths on which human HDL
      biology may be investigated leading to convenient biomarkers of HDL quality and
      function having potential not only to improve risk prediction but also to more
      accurately target drug treatments.

PMID- 29371249
TI  - A Poly(A) Ribonuclease Controls the Cellotriose-Based Interaction between
      Piriformospora indica and Its Host Arabidopsis.
AB  - Piriformospora indica, an endophytic root-colonizing fungus, efficiently promotes
      plant growth and induces resistance to abiotic stress and biotic diseases. P.
      indica fungal cell wall extract induces cytoplasmic calcium elevation in host
      plant roots. Here, we show that cellotriose (CT) is an elicitor-active cell wall
      moiety released by P. indica into the medium. CT induces a mild defense-like
      response, including the production of reactive oxygen species, changes in
      membrane potential, and the expression of genes involved in growth regulation and
      root development. CT-based cytoplasmic calcium elevation in Arabidopsis
      (Arabidopsis thaliana) roots does not require the BAK1 coreceptor or the putative
      Ca2+ channels TPC1, GLR3.3, GLR2.4, and GLR2.5 and operates synergistically with
      the elicitor chitin. We identified an ethyl methanesulfonate-induced mutant
      (cytoplasmiccalcium elevation mutant) impaired in the response to CT and various
      other cellooligomers (n = 2-7), but not to chitooligomers (n = 4-8), in roots.
      The mutant contains a single nucleotide exchange in the gene encoding a poly(A)
      ribonuclease (AtPARN; At1g55870) that degrades the poly(A) tails of specific
      mRNAs. The wild-type PARN cDNA, expressed under the control of a 35S promoter,
      complements the mutant phenotype. Our identification of cellotriose as a novel
      chemical mediator casts light on the complex P. indica-plant mutualistic
      relationship.

PMID- 29371252
TI  - Looking Deep into the Eye-of-the-Tiger in Pantothenate Kinase-Associated
      Neurodegeneration.
AB  - BACKGROUND AND PURPOSE: A detailed delineation of the MR imaging changes in the
      globus pallidus in pantothenate kinase-associated neurodegeneration will be
      helpful for diagnosis and monitoring of patients. The aim of this study was to
      determine the morphologic spectrum of the "eye-of-the-tiger" sign and the
      topographic pattern of iron deposition in a group of patients with pantothenate
      kinase-associated neurodegeneration. MATERIALS AND METHODS: Seventy-four MR
      imaging scans from 54 individuals with PANK2 mutations were analyzed for signal
      patterns in the globus pallidus. Sixteen SWI data from 15 patients who underwent
      1.5T (n = 7), 3T (n = 7), and 7T (n = 2) MR imaging were included to visualize
      the iron topography. RESULTS: The linear hyperintensity alongside the medial
      border of the globus pallidus was the earliest T2 signal change. This finding was
      evident before SWI changes from iron deposition became visible. T2WI performed in
      early childhood mostly showed isolated hyperintense signal. In adult patients,
      marked signal reduction within an earlier hyperintense center resulting from iron
      accumulation led to the loss of signal difference between the central and
      surrounding areas. Signal hypointensity on SWI progressed from the medial to the
      lateral portion of the globus pallidus with increasing age. The fiber connections
      between the medial globus pallidus and the anteromedial aspect of the substantia
      nigra and subthalamic nucleus were markedly hypointense on SWI. CONCLUSIONS: In
      pantothenate kinase-associated neurodegeneration, the globus pallidus MR imaging
      changes using SWI develop as region-specific and age-dependent phenomena. Signal
      inhomogeneity was observed across the globus pallidus in pantothenate kinase
      associated neurodegeneration and should be considered when determining the
      concentration of iron.

PMID- 29371251
TI  - Intravoxel Incoherent Motion MR Imaging in the Differentiation of Benign and
      Malignant Sinonasal Lesions: Comparison with Conventional Diffusion-Weighted MR
      Imaging.
AB  - BACKGROUND AND PURPOSE: Intravoxel incoherent motion is a promising method for
      the differentiation of sinonasal lesions. This study aimed to evaluate the value
      of intravoxel incoherent motion in the differentiation of benign and malignant
      sinonasal lesions and to compare the diagnostic performance of intravoxel
      incoherent motion with that of conventional DWI. MATERIALS AND METHODS: One
      hundred thirty-one patients with histologically proved solid sinonasal lesions
      (56 benign and 75 malignant) who underwent conventional DWI and intravoxel
      incoherent motion were recruited in this study. The diffusion coefficient (D),
      pseudodiffusion coefficient (D*), and perfusion fraction (f) values derived from
      intravoxel incoherent motion and ADC values derived from conventional DWI were
      measured and compared between the 2 groups using the Student t test. Receiver
      operating characteristic curve analysis, logistic regression analysis, and 10
      fold cross-validation were performed to evaluate the diagnostic performance of
      single-parametric and multiparametric models. RESULTS: The mean ADC and D values
      were significantly lower in malignant sinonasal lesions than in benign sinonasal
      lesions (both P < .001). The mean f value was higher in malignant lesions than in
      benign lesions (P = .003). Multiparametric models can significantly improve the
      cross-validated areas under the curve for the differentiation of sinonasal
      lesions compared with single-parametric models (all corrected P < .05 except the
      D value). The model of D+f provided a better diagnostic performance than the ADC
      value (corrected P < .001). CONCLUSIONS: Intravoxel incoherent motion appears to
      be a more effective MR imaging technique than conventional DWI in the
      differentiation of benign and malignant sinonasal lesions.

PMID- 29371250
TI  - Acclimation to Fluctuating Light Impacts the Rapidity of Response and Diurnal
      Rhythm of Stomatal Conductance.
AB  - Plant acclimation to growth light environment has been studied extensively;
      however, the majority of these studies have focused on light intensity and photo
      acclimation, with few studies exploring the impact of dynamic growth light on
      stomatal acclimation and behavior. To assess the impact of growth light regime on
      stomatal acclimation, we grew Arabidopsis (Arabidopsis thaliana) plants in three
      different lighting regimes (with the same average daily intensity), fluctuating
      with a fixed pattern of light, fluctuating with a randomized pattern of light
      (sinusoidal), and nonfluctuating (square wave), to assess the effect of light
      regime dynamics on gas exchange. We demonstrated that gs (stomatal conductance to
      water vapor) acclimation is influenced by both intensity and light pattern,
      modifying the stomatal kinetics at different times of the day and resulting in
      differences in the rapidity and magnitude of the gs response. We also describe
      and quantify the response to an internal signal that uncouples variation in A and
      gs over the majority of the diurnal period and represents 25% of the total
      diurnal gs This gs response can be characterized by a Gaussian element and when
      incorporated into the widely used Ball-Berry model greatly improved the
      prediction of gs in a dynamic environment. From these findings, we conclude that
      acclimation of gs to growth light could be an important strategy for maintaining
      carbon fixation and overall plant water status and should be considered when
      inferring responses in the field from laboratory-based experiments.

PMID- 29371253
TI  - Comparison of MR Imaging and Dual-Energy CT for the Evaluation of Cartilage
      Invasion by Laryngeal and Hypopharyngeal Squamous Cell Carcinoma.
AB  - BACKGROUND AND PURPOSE: Dual-energy CT can distinguish iodine-enhanced tumors
      from nonossified cartilage and has been investigated for evaluating cartilage
      invasion in patients with laryngeal and hypopharyngeal squamous cell carcinomas.
      In this study, we compared the diagnostic accuracy of MR imaging and of a
      combination of weighted-average and iodine overlay dual-energy CT images in
      detecting cartilage invasion by laryngeal and hypopharyngeal squamous cell
      carcinomas, in particular thyroid cartilage invasion. MATERIALS AND METHODS:
      Fifty-five consecutive patients who underwent 3T MR imaging and 128-slice dual
      energy CT for preoperative initial staging of laryngeal or hypopharyngeal
      squamous cell carcinomas were included. Two blinded observers evaluated laryngeal
      cartilage invasion on MR imaging and dual-energy CT using a combination of
      weighted-average and iodine-overlay images. Pathologic findings of surgically
      resected specimens were used as the reference standard for evaluating
      sensitivity, specificity, and the areas under the receiver operating
      characteristic curve of both modalities for cartilage invasion by each type of
      cartilage and for all cartilages together. Sensitivity and specificity were
      compared using the McNemar test and generalized linear mixed models. RESULTS:
      Dual-energy CT showed higher specificity than MR imaging for diagnosing all
      cartilage together (84% for MR imaging versus 98% for dual-energy CT, P < .004)
      and for thyroid cartilage (64% versus 100%, P < .001), with a similar average
      area under the curve (0.94 versus 0.95, P = .70). The sensitivity did not differ
      significantly for all cartilages together (97% versus 81%, P = .16) and for
      thyroid cartilage (100% versus 89%, P = .50), though there was a trend toward
      increased sensitivity with MR imaging. CONCLUSIONS: Dual-energy CT showed higher
      specificity and acceptable sensitivity in diagnosing laryngeal cartilage invasion
      compared with MR imaging.

PMID- 29371255
TI  - Nonsphericity Index and Size Ratio Identify Morphologic Differences between
      Growing and Stable Aneurysms in a Longitudinal Study of 93 Cases.
AB  - BACKGROUND AND PURPOSE: Recent studies have strongly associated intracranial
      aneurysm growth with increased risk of rupture. Identifying aneurysms that are
      likely to grow would be beneficial to plan more effective monitoring and
      intervention strategies. Our hypothesis is that for unruptured intracranial
      aneurysms of similar size, morphologic characteristics differ between aneurysms
      that continue to grow and those that do not. MATERIALS AND METHODS: From
      aneurysms in our medical center with follow-up imaging dates in 2015, ninety
      three intracranial aneurysms (23 growing, 70 stable) were selected. All CTA
      images for the aneurysm diagnosis and follow-up were collected, a total of 348 3D
      imaging studies. Aneurysm 3D geometry for each imaging study was reconstructed,
      and morphologic characteristics, including volume, surface area, nonsphericity
      index, aspect ratio, and size ratio were calculated. RESULTS: Morphologic
      characteristics were found to differ between growing and stable groups. For
      aneurysms of <3 mm, nonsphericity index (P < .001); 3-5 mm, nonsphericity index
      (P < .001); 5-7 mm, size ratio (P = .003); >7 mm, volume (P < .001); surface area
      (P < .001); and nonsphericity index (P = .002) were significant. Within the
      anterior communicating artery, the nonsphericity index (P = .008) and, within the
      posterior communicating artery, size ratio (P = .004) were significant. The
      nonsphericity index receiver operating characteristic area under the curve was
      0.721 for discriminating growing and stable cases on the basis of initial images.
      CONCLUSIONS: Among aneurysms with similar sizes, morphologic characteristics
      appear to differ between those that are growing and those that are stable. The
      nonsphericity index, in particular, was found to be higher among growing
      aneurysms. The size ratio was found to be the second most significant parameter
      associated with growth.

PMID- 29371254
TI  - Local Glioma Cells Are Associated with Vascular Dysregulation.
AB  - BACKGROUND AND PURPOSE: Malignant glioma is a highly infiltrative malignancy that
      causes variable disruptions to the structure and function of the
      cerebrovasculature. While many of these structural disruptions have known
      correlative histopathologic alterations, the mechanisms underlying vascular
      dysfunction identified by resting-state blood oxygen level-dependent imaging are
      not yet known. The purpose of this study was to characterize the alterations that
      correlate with a blood oxygen level-dependent biomarker of vascular
      dysregulation. MATERIALS AND METHODS: Thirty-two stereotactically localized
      biopsies were obtained from contrast-enhancing (n = 16) and nonenhancing (n = 16)
      regions during open surgical resection of malignant glioma in 17 patients.
      Preoperative resting-state blood oxygen level-dependent fMRI was used to evaluate
      the relationships between radiographic and histopathologic characteristics.
      Signal intensity for a blood oxygen level-dependent biomarker was compared with
      scores of tumor infiltration and microvascular proliferation as well as total
      cell and neuronal density. RESULTS: Biopsies corresponded to a range of blood
      oxygen level-dependent signals, ranging from relatively normal (z = -4.79) to
      markedly abnormal (z = 8.84). Total cell density was directly related to blood
      oxygen level-dependent signal abnormality (P = .013, R2 = 0.19), while the
      neuronal labeling index was inversely related to blood oxygen level-dependent
      signal abnormality (P = .016, R2 = 0.21). The blood oxygen level-dependent signal
      abnormality was also related to tumor infiltration (P = .014) and microvascular
      proliferation (P = .045). CONCLUSIONS: The relationship between local, neoplastic
      characteristics and a blood oxygen level-dependent biomarker of vascular function
      suggests that local effects of glioma cell infiltration contribute to vascular
      dysregulation.

PMID- 29371256
TI  - Comparison of Blood Oxygenation Level-Dependent fMRI and Provocative DSC
      Perfusion MR Imaging for Monitoring Cerebrovascular Reserve in Intracranial
      Chronic Cerebrovascular Disease.
AB  - BACKGROUND AND PURPOSE: Loss of hemodynamic reserve in intracranial
      cerebrovascular disease reduces blood oxygenation level-dependent activation by
      fMRI and increases asymmetry in MTT measured by provocative DSC perfusion MR
      imaging before and after vasodilation with intravenous acetazolamide. The
      concordance for detecting hemodynamic reserve integrity has been compared.
      MATERIALS AND METHODS: Patients (n = 40) with intracranial cerebrovascular
      disease and technically adequate DSA, fMRI and provocative DSC perfusion studies
      were retrospectively grouped into single vessels proximal to and distal from the
      circle of Willis, multiple vessels, and Moyamoya disease. The vascular
      territories were classified as having compromised hemodynamic reserve if the
      expected fMRI blood oxygenation level-dependent activation was absent or if MTT
      showed increased asymmetry following vasodilation. Concordance was examined in
      compromised and uncompromised vascular territories of each group with the Fischer
      exact test and proportions of agreement. RESULTS: Extensive leptomeningeal
      collateral circulation was present in all cases. Decreased concordance between
      the methods was found in vascular territories with stenosis distal to but not
      proximal to the circle of Willis. Multivessel and Moyamoya diseases also showed
      low concordance. A model of multiple temporally displaced arterial inputs from
      leptomeningeal collateral flow demonstrated that the resultant lengthening MTT
      mimicked compromised hemodynamic reserve despite being sufficient to support
      blood oxygenation level-dependent contrast. CONCLUSIONS: Decreased concordance
      between the 2 methods for assessment of hemodynamic reserve for vascular disease
      distal to the circle of Willis is posited to be due to well-developed
      leptomeningeal collateral circulation providing multiple temporally displaced
      arterial input functions that bias the perfusion analysis toward hemodynamic
      reserve compromise while blood oxygenation level-dependent activation remains
      detectable.

PMID- 29371257
TI  - Early Hemodynamic Response Assessment of Stereotactic Radiosurgery for a Cerebral
      Arteriovenous Malformation Using 4D Flow MRI.
AB  - Brain AVMs treated with stereotactic radiosurgery typically demonstrate a minimum
      latency period of 1-3 years between treatment and nidus obliteration. Assessment
      of treatment response is usually limited to evaluation of AVM nidus structural
      changes using conventional MR imaging and MRA techniques. This report describes
      the use of 4D Flow MRI to also measure radiation-induced hemodynamic changes in a
      Spetzler-Martin grade III AVM, which were detectable as early as 6 months after
      treatment.

PMID- 29371258
TI  - Quantitative Susceptibility Mapping of the Thalamus: Relationships with Thalamic
      Volume, Total Gray Matter Volume, and T2 Lesion Burden.
AB  - BACKGROUND AND PURPOSE: Both thalamic iron deposition and atrophy have been
      reported in patients with multiple sclerosis compared with healthy controls, but
      how they are related is unclear. The purpose of this study was to understand the
      pathophysiologic basis for this iron deposition. MATERIALS AND METHODS: Ninety
      five patients with relapsing-remitting multiple sclerosis underwent 3T MR imaging
      with a standardized protocol that included quantitative susceptibility mapping to
      measure iron concentration and a 3D T1 echo-spoiled gradient-echo sequence to
      obtain thalamic volumes. Volumes of interest were manually delineated on the
      quantitative susceptibility map to encompass both thalami. Multivariate
      regression analyses were performed to identify the association between thalamic
      susceptibility and volume. Associations between thalamic susceptibility and total
      gray matter volume, cortical thickness, and T2 lesion volume were also assessed.
      RESULTS: The relative susceptibility of the thalamus was associated with T2
      lesion volume (P = .015) and was higher in the presence of enhancing lesions (P =
      .013). The relative susceptibility of the thalami was not associated with
      thalamic volumes, total gray matter volumes, or cortical thickness (P > .05).
      CONCLUSIONS: Iron levels in the thalami are associated with T2 lesion burden and
      the presence of enhancing lesions, but not with thalamic or gray matter volumes,
      suggesting that iron accumulation is associated with white matter inflammation
      rather than gray matter neurodegeneration.

PMID- 29371259
TI  - Melanoma of the Sinonasal Tract: Value of a Septate Pattern on Precontrast T1
      Weighted MR Imaging.
AB  - BACKGROUND AND PURPOSE: Various tumors of the sinonasal tract can exhibit high
      signal intensity on T1WI. The purpose of this study was to determine the value of
      a septate pattern on precontrast T1WI for diagnosing sinonasal melanoma.
      MATERIALS AND METHODS: Retrospectively, 3 observers independently reviewed MR
      images of 31 histologically proved sinonasal melanomas with special attention to
      the presence or absence of a septate pattern on precontrast T1WI, defined as
      alternating hyperintense and hypointense striations on precontrast T1WI. For
      comparison, we evaluated the prevalence of a septate pattern on precontrast T1WI
      in 106 nonmelanomatous sinonasal malignant tumors with 16 different histologic
      types. We also tried to identify the histopathologic features responsible for the
      septate pattern on precontrast T1WI. RESULTS: Twenty-seven (87.1%) of 31
      sinonasal melanomas showed hyperintense foci on T1WI, among which a septate
      pattern on precontrast T1WI was seen in 23 (74.2%), while 22 (20.8%) of 106
      nonmelanomatous malignant tumors demonstrated hyperintense foci on T1WI, among
      which only 3 (2.8%) showed a septate pattern on precontrast T1WI. The
      sensitivity, specificity, positive predictive value, negative predictive value,
      and accuracy of a septate pattern on precontrast T1WI for the diagnosis of
      sinonasal melanoma were 74%, 97%, 88%, 93%, and 92%, respectively. Although
      limited due to the retrospective nature, 4 of 23 histologically reviewed
      sinonasal melanomas revealed an uneven distribution of melanin with alternating
      melanin and fibrous bands within the tumors. CONCLUSIONS: A septate pattern on
      precontrast T1WI might be an adjunctive imaging finding for the diagnosis of
      sinonasal melanoma. This might be attributed histologically to an uneven
      distribution of melanin and hemorrhage within the tumors.

PMID- 29371260
TI  - The Antigen ASB4 on Cancer Stem Cells Serves as a Target for CTL Immunotherapy of
      Colorectal Cancer.
AB  - Colorectal cancer consists of a small number of cancer stem cells (CSC) and many
      non-CSCs. Although rare in number, CSCs are a target for cancer therapy, because
      they survive conventional chemo- and radiotherapies and perpetuate tumor
      formation in vivo In this study, we conducted an HLA ligandome analysis to survey
      HLA-A24 peptides displayed by CSCs and non-CSCs of colorectal cancer. The
      analysis identified an antigen, ASB4, which was processed and presented by a CSC
      subset but not by non-CSCs. The ASB4 gene was expressed in CSCs of colorectal
      cancer, but not in cells that had differentiated into non-CSCs. Because ASB4 was
      not expressed by normal tissues, its peptide epitope elicited CD8+ cytotoxic T
      cell (CTL) responses, which lysed CSCs of colorectal cancer and left non-CSCs
      intact. Therefore, ASB4 is a tumor-associated antigen that can elicit CTL
      responses specific to CSCs and can discriminate between two cellular subsets of
      colorectal cancer. Adoptively transferred CTLs specific for the CSC antigen ASB4
      could infiltrate implanted colorectal cancer cell tumors and effectively
      prevented tumor growth in a mouse model. As the cancer cells implanted in these
      mice contained very few CSCs, the elimination of a CSC subset could be the
      condition necessary and sufficient to control tumor formation in vivo These
      results suggest that CTL-based immunotherapies against colorectal CSCs might be
      useful for preventing relapses. Cancer Immunol Res; 1-12. (c)2018 AACR.

PMID- 29371261
TI  - Welcome to BMJ Evidence-Based Medicine.

PMID- 29371262
TI  - Women, their Offspring and iMproving lifestyle for Better cardiovascular health
      of both (WOMB project): a protocol of the follow-up of a multicentre randomised
      controlled trial.
AB  - INTRODUCTION: Women, their Offspring and iMproving lifestyle for Better
      cardiovascular health of both (WOMB) project is the follow-up of the LIFEstyle
      study, a randomised controlled trial in obese infertile women, and investigates
      the effects of a preconception lifestyle intervention on later health of women
      (WOMB women) and their children (WOMB kids). METHODS AND ANALYSIS: Obese
      infertile women, aged between 18 and 39 years, were recruited in 23 Dutch
      fertility clinics between June 2009 and June 2012. The 284 women allocated to the
      intervention group received a 6-month structured lifestyle programme. The 280
      women in the control group received infertility care as usual. 4 to 7 years after
      inclusion in the trial, all women (n=564) and children conceived during the trial
      (24 months after randomisation) (n=305 singletons and age 3-5 years) will be
      approached to participate in this follow-up study (starting in 2015). The main
      focus of outcome will be cardiovascular health, but the dataset comprises a wide
      range of physical and mental health measures, diet and physical activity
      measures, child growth and development measures, biological samples and genetic
      and epigenetic information. The follow-up assessment consists of three stages
      that take place between 2016 and 2018, and includes (online) questionnaires,
      accelerometry and physical and behavioural measurements in a mobile research
      vehicle. A subsample of 100 women and 100 children are planned for cardiac
      ultrasound measurements. ETHICS AND DISSEMINATION: The protocol of this follow-up
      study is approved by the local medical ethics committee (University Medical
      Centre Groningen). Study findings of the WOMB project will be widely disseminated
      to the scientific community, healthcare professionals, policy makers, future
      parents and general public. TRIAL REGISTRATION NUMBER: The original LIFEstyle
      study is registered at The Netherlands Trial Registry (number 1530).

PMID- 29371264
TI  - Effectiveness of a nurse-supported self-management programme for dual sensory
      impaired older adults in long-term care: a cluster randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a nurse-supported self-management
      programme to improve social participation of dual sensory impaired older adults
      in long-term care homes. DESIGN: Cluster randomised controlled trial. SETTING:
      Thirty long-term care homes across the Netherlands. PARTICIPANTS: Long-term care
      homes were randomised into intervention clusters (n=17) and control clusters
      (n=13), involving 89 dual sensory impaired older adults and 56 licensed practical
      nurses. INTERVENTION: Nurse-supported self-management programme. MEASUREMENTS:
      Effectiveness was evaluated by the primary outcome social participation using a
      participation scale adapted for visually impaired older adults distinguishing
      four domains: instrumental activities of daily living, social-cultural
      activities, high-physical-demand and low-physical-demand leisure activities. A
      questionnaire assessing hearing-related participation problems was added as
      supportive outcome. Secondary outcomes were autonomy, control, mood and quality
      of life and nurses' job satisfaction. For effectiveness analyses, linear mixed
      models were used. Sampling and intervention quality were analysed using
      descriptive statistics. RESULTS: Self-management did not affect all four domains
      of social participation; however. the domain 'instrumental activities of daily
      living' had a significant effect in favour of the intervention group (P=0.04; 95%
      CI 0.12 to 8.5). Sampling and intervention quality was adequate. CONCLUSIONS: A
      nurse-supported self-management programme was effective in empowering the dual
      sensory impaired older adults to address the domain 'instrumental activities of
      daily living', but no differences were found in addressing the other three
      participation domains. Self-management showed to be beneficial for managing
      practical problems, but not for those problems requiring behavioural adaptations
      of other persons. TRIAL REGISTRATION NUMBER: NCT01217502; Results.

PMID- 29371263
TI  - Tulsa 1000: a naturalistic study protocol for multilevel assessment and outcome
      prediction in a large psychiatric sample.
AB  - INTRODUCTION: Although neuroscience has made tremendous progress towards
      understanding the basic neural circuitry underlying important processes such as
      attention, memory and emotion, little progress has been made in applying these
      insights to psychiatric populations to make clinically meaningful treatment
      predictions. The overall aim of the Tulsa 1000 (T-1000) study is to use the NIMH
      Research Domain Criteria framework in order to establish a robust and reliable
      dimensional set of variables that quantifies the positive and negative valence,
      cognition and arousal domains, including interoception, to generate clinically
      useful treatment predictions. METHODS AND ANALYSIS: The T-1000 is a naturalistic
      study that will recruit, assess and longitudinally follow 1000 participants,
      including healthy controls and treatment-seeking individuals with mood, anxiety,
      substance use and eating disorders. Each participant will undergo interview,
      behavioural, biomarker and neuroimaging assessments over the course of 1 year.
      The study goal is to determine how disorders of affect, substance use and eating
      behaviour organise across different levels of analysis (molecules, genes, cells,
      neural circuits, physiology, behaviour and self-report) to predict symptom
      severity, treatment outcome and long-term prognosis. The data will be used to
      generate computational models based on Bayesian statistics. The final end point
      of this multilevel latent variable analysis will be standardised assessments that
      can be developed into clinical tools to help clinicians predict outcomes and
      select the best intervention for each individual, thereby reducing the burden of
      mental disorders, and taking psychiatry a step closer towards personalised
      medicine. ETHICS AND DISSEMINATION: Ethical approval was obtained from Western
      Institutional Review Board screening protocol #20101611. The dissemination plan
      includes informing health professionals of results for clinical practice,
      submitting results to journals for peer-reviewed publication, presenting results
      at national and international conferences and making the dataset available to
      researchers and mental health professionals. TRIAL REGISTRATION NUMBER:
      NCT02450240; Pre-results.

PMID- 29371265
TI  - Social participation and risk of influenza infection in older adults: a cross
      sectional study.
AB  - OBJECTIVES: Influenza infection can cause severe pneumonia, which is sometimes
      fatal, particularly in older adults. Influenza results in 3-5 million cases of
      severe illness and about 250 000 to 500 000 deaths annually worldwide. Social
      participation in the context of influenza infection is controversial because,
      although social participation is beneficial in maintaining physical function and
      mental health, it also increases the risk of contact with infected people. This
      study examined the association between social participation and influenza
      infection in Japanese adults aged 65 years or older. DESIGN: Cross-sectional
      study. SETTING: Japanese functionally independent adults aged 65 years or older.
      PARTICIPANTS: Among the respondents to the Japan Gerontological Evaluation Study
      (JAGES) 2013 survey, which took place during the period from October to December
      2013, 12 231 men and 14 091 women responded to questions on influenza vaccination
      and influenza infection. OUTCOME MEASURES: Using JAGES data for 12 231 men and 14
      091 women aged >=65 years, we examined the association between social
      participation and influenza infection. The association between influenza
      infection and number of groups in which respondents participated was investigated
      among adults aged>=65 years, stratified by vaccination status and sex. RESULTS:
      Unvaccinated women who participated in two or more social activities were 2.20
      times (95% CI 1.47 to 3.29) as likely to report an influenza infection as those
      who reported no social participation. In contrast, vaccinated women who
      participated in two or more social groups had no additional risk of influenza
      infection as compared with female elders with no social participation. Among men,
      participation in social activities was not significantly associated with
      influenza infection, regardless of vaccination status. CONCLUSIONS: Social
      participation was associated with a higher risk of influenza infection among
      unvaccinated older women, which suggests a need for further efforts to promote
      influenza vaccination, particularly among socially active elderly women.

PMID- 29371266
TI  - Disease and age pattern of hospitalisation and associated costs in India: 1995
      2014.
AB  - OBJECTIVES: The prime objective of this study is to examine the trends of disease
      and age pattern of hospitalisation and associated costs in India during 1995
      2014. DESIGN: Present study used nationally representative data on morbidity and
      healthcare from the 52nd (1995) and 71st (2014) rounds of the National Sample
      Survey. SETTINGS: A total of 120 942 and 65 932 households were surveyed in 1995
      and 2014, respectively. MEASURES: Descriptive statistics, logistic regression
      analyses and decomposition analyses were used in examining the changes in
      patterns of hospitalisation and associated costs. Hospitalisation rates and costs
      per hospitalisation (out-of-pocket expenditure) were estimated for selected
      diseases and in four broad categories: communicable diseases, non-communicable
      diseases (NCDs), injuries and others. All the costs are presented at 2014 prices
      in US$. RESULTS: Hospitalisation rate in India has increased from 1661 in 1995 to
      3699 in 2014 (per 100 000 population). It has more than doubled across all age
      groups. Hospitalisation among children was primarily because of communicable
      diseases, while NCDs were the leading cause of hospitalisation for the 40+
      population. Costs per hospitalisation have increased from US$177 in 1995 to
      US$316 in 2014 (an increase of 79%). Costs per hospitalisation for NCDs in 2014
      were US$471 compared with US$175 for communicable diseases. It was highest for
      cancer inpatients (US$942) followed by heart diseases (US$674). Age is the
      significant predictor of hospitalisation for all the selected diseases.
      Decomposition results showed that about three-fifth of the increase in
      unconditional costs per hospitalisation was due to increase in mean hospital
      costs, and the other two-fifth was due to increase in hospitalisation rates.
      CONCLUSION: There has been more than twofold increase in hospitalisation rates in
      India during the last two decades, and significantly higher rates were observed
      among infants and older adults. Increasing hospitalisation rates and costs per
      hospitalisation are contributing substantially to the rising healthcare costs in
      India.

PMID- 29371267
TI  - Electroacupuncture as an adjunctive therapy for motor dysfunction in acute stroke
      survivors: a systematic review and meta-analyses.
AB  - OBJECTIVES: To assess the effectiveness and safety of electroacupuncture (EA)
      combined with rehabilitation therapy (RT) and/or conventional drugs (CD) for
      improving poststroke motor dysfunction (PSMD). DESIGN: Systematic review and meta
      analysis. METHODS: The China National Knowledge Infrastructure, Chinese
      Biological Medicine Database, Chinese Scientific Journal Database, Cochrane
      Library, Medline and Embase were electronically searched from inception to
      December 2016. The methodological quality of the included trials was assessed
      using the Cochrane risk of bias assessment tool. Statistical analyses were
      performed by RevMan V.5.3 and Stata SE V.11.0. RESULTS: Nineteen trials with 1434
      participants were included for qualitative synthesis and meta-analysis. The
      methodological quality of the included trials was generally poor. The meta
      analysis indicated that the EA group might be benefiting more than the non-EA
      group in terms of the changes in the Fugl-Meyer Assessment Scale (FMA) (weighted
      mean difference (WMD): 10.79, 95% CI 6.39 to 15.20, P<0.001), FMA for lower
      extremity (WMD: 5.16, 95% CI 3.78 to 6.54, P<0.001) and activities of daily
      living (standardised mean difference: 1.37, 95% CI 0.79 to 1.96, P<0.001).
      However, there was no difference between EA and non-EA groups in terms of the
      effective rate (relative risk: 1.13, 95% CI 1.00 to 1.27, P=0.050). Moreover,
      there were not any reports of side effects due to EA combined with RT and/or CD
      in the included trials. CONCLUSIONS: This review provides new evidence for the
      effectiveness and safety of EA combined with RT and/or CD for PSMD. However, the
      results should be interpreted cautiously because of methodological weakness and
      publication bias. Further clinical trials with a rigorous design and large sample
      sizes are warranted. PROSPERO REGISTRATION NUMBER: CRD42016037597.

PMID- 29371268
TI  - Longitudinal designs to study neighbourhood effects on the development of
      obesity: a scoping review protocol.
AB  - INTRODUCTION: The prevalence of obesity has increased significantly in the last
      three decades and became an important public health concern. Evidence of weight
      status variability at the neighbourhood level has led researchers to look more
      precisely at the characteristics of local geographic areas that might influence
      energy balance related behaviours, giving rise to the field of the 'neighbourhood
      effect' in public health research. Among an abundant literature about
      neighbourhood effects and obesity, we propose a protocol for a scoping review
      that will aim at determining how temporal measurements of residential
      neighbourhood exposure, individual covariates and weight outcome are integrated
      in longitudinal designs. METHODS AND ANALYSIS: A list of relevant citations will
      be obtained through a comprehensive systematic database search in Pubmed, Web of
      Science and Embase. The search strategy will be designed using a broad definition
      of neighbourhood to take into account the heterogeneity of this concept in
      research. Two investigators will screen titles, abstracts and entire publications
      using predetermined eligibility criteria yielding a list of selected
      publications. Data from the publications included in the scoping review will be
      charted according to bibliographic information, study population, exposure,
      outcomes and results. DISCUSSION AND CONCLUSION: To our knowledge, our protocol
      will yield the first scoping review regarding longitudinal designs of
      neighbourhood effect on obesity. Describing how longitudinal designs include
      temporal measurements of exposure, covariates and outcome is a necessary step in
      the quest to determine if or which contextual characteristics are likely to be
      involved in the development of obesity. Such information would bring new
      knowledge to complement current aetiological investigations and would contribute
      to enhancing resource allocation strategies for stakeholders in developing
      relevant interventions to prevent obesity and its negative impacts.

PMID- 29371269
TI  - Attitudes and barriers to exercise in adults with a recent diagnosis of type 1
      diabetes: a qualitative study of participants in the Exercise for Type 1 Diabetes
      (EXTOD) study.
AB  - OBJECTIVES: To explore attitudes and barriers to exercise in adults with new
      onset type 1 diabetes mellitus (T1DM). DESIGN: Qualitative methodology using
      focus group (n=1), individual face-to-face (n=4) and telephone interviews (n=8).
      Thematic analysis using the Framework Method. SETTING: Nineteen UK hospital
      sites. PARTICIPANTS: Fifteen participants in the Exercise for Type 1 Diabetes
      study. We explored current and past levels of exercise, understanding of exercise
      and exercise guidelines, barriers to increasing exercise levels and preferences
      for monitoring of activity in a trial. RESULTS: Five main themes were identified:
      existing attitudes to exercise, feelings about diagnosis, perceptions about
      exercise consequences, barriers to increasing exercise and confidence in managing
      blood glucose. An important finding was that around half the participants
      reported a reduction in activity levels around diagnosis. Although exercise was
      felt to positively impact on health, some participants were not sure about the
      benefits or concerned about potential harms such as hypoglycaemia. Some
      participants reported being advised by healthcare practitioners (HCPs) not to
      exercise. CONCLUSIONS: Exercise should be encouraged (not discouraged) from
      diagnosis, as patients may be more amenable to lifestyle change. Standard advice
      on exercise and T1DM needs to be made available to HCPs and patients with T1DM to
      improve patients' confidence in managing their diabetes around exercise. TRIAL
      REGISTRATION NUMBER: ISRCTN91388505; Results.

PMID- 29371270
TI  - Diagnostic markers of acute infections in infants aged 1 week to 3 months: a
      retrospective cohort study.
AB  - OBJECTIVE: History and physical examination do not reliably exclude serious
      bacterial infections (SBIs) in infants. We examined potential markers of SBI in
      young febrile infants. DESIGN: We reviewed white cell count (WBC), absolute
      neutrophil count (ANC), neutrophil to lymphocyte count ratio (NLR) and C reactive
      protein (CRP) in infants aged 1 week to 90 days, admitted for fever to one
      medical centre during 2012-2014. RESULTS: SBI was detected in 111 (10.6%) of 1039
      infants. Median values of all investigated diagnostic markers were significantly
      higher in infants with than without SBI: WBC (14.4 vs 11.4 K/uL, P<0.001), ANC
      (5.8 vs 3.7 K/uL, P<0.001), CRP (19 vs 5 mg/L, P <0.001) and NLR (1.2 vs 0.7,
      P<0.001). Areas under the receiver operating characteristic curve (AUC) for
      discriminating SBI were: 0.65 (95% CI 0.59 to 0.71), 0.69 (95% CI 0.63 to 0.74),
      0.71 (95% CI 0.65 to 0.76) and 0.66 (95% CI 0.60 to 0.71) for WBC, ANC, CRP and
      NLR, respectively. Logistic regression showed the best discriminative ability for
      the combination of CRP and ANC, with AUC: 0.73 (95% CI 0.67 to 0.78). For
      invasive bacterial infection, AUCs were 0.70 (95% CI 0.56 to 0.85), 0.80 (95% CI
      0.67 to 0.92), 0.78 (95% CI 0.68 to 0.89) and 0.78 (95% CI 0.66 to 0.90),
      respectively. CRP combined with NLR or ANC were the best discriminators of
      infection, AUCs: 0.82 (95% CI 0.70 to 0.95) and 0.82 (95% CI 0.68 to 0.95),
      respectively. CONCLUSIONS: Among young febrile infants, CRP was the best single
      discriminatory marker of SBI, and ANC was the best for invasive bacterial
      infection. ANC and NLR can contribute to evaluating this population.

PMID- 29371271
TI  - Quality of life of elderly patients with solid tumours undergoing adjuvant cancer
      therapy: a systematic review.
AB  - OBJECTIVES: The measurement of quality of life (QoL) in elderly cancer population
      is increasingly being recognised as an important element of clinical decision
      making and the evaluation of treatment outcome. This systematic review aimed to
      summarise the evidence of QoL during and after adjuvant therapy in elderly
      patients with cancer. METHODS: A systematic search was conducted of studies
      published in CINAHL plus, CENTRAL, PubMed, PsycINFO and Web of Science from the
      inception of these databases to December 2016. Eligible studies included RCTs and
      non-RCTs in which QoL was measured in elderly patients (aged 65 years or above)
      with stage I-III solid tumours who were undergoing adjuvant chemotherapy and/or
      radiotherapy. Because of the heterogeneity and the insufficient data among the
      included studies, the results were synthesised narratively. RESULTS: We included
      4 RCTs and 14 non-RCTs on 1785 participants. In all four RCTs, the risk of bias
      was low or unclear for most items but high for detection. Of the 14 non-RCTs, 5
      studies were judged to have a low or moderate risk of bias for all domains, and
      the other 9 studies had a serious risk of bias in at least one domain. The bias
      was observed mainly in the confounding and in the selection of participants for
      the study. For most elderly patients with breast cancer, the non-significant
      negative change in the QoL was transient. A significant increase in the QoL
      during the course of temozolomide in elderly patients with glioblastoma but a
      decreasing trend in QoL after radiotherapy was shown. This review also shows a
      uniform trend of stable or improved QoL during adjuvant therapy and at follow-up
      evaluations across the studies with prostate, colon or cervical cancer
      population. CONCLUSIONS: This review suggests that adjuvant chemotherapy and
      radiotherapy may not have detrimental effects on QoL in most elderly patients
      with solid tumours.

PMID- 29371272
TI  - Comparison of two methods to assess physical activity prevalence in children: an
      observational study using a nationally representative sample of Scottish children
      aged 10-11 years.
AB  - OBJECTIVES: To describe the objectively measured levels of physical activity (PA)
      and sedentary time in a nationally representative sample of 10-11-year-old
      children, and compare adherence estimates to the UK PA guidelines using two
      approaches to assessing prevalence. DESIGN: Nationally representative
      longitudinal cohort study. SETTING: Scotland wide in partnership with the Growing
      up in Scotland (GUS) study. Data collection took place between May 2015 and May
      2016. PARTICIPANTS: The parents of 2402 GUS children were approached and 2162
      consented to contact. Consenting children (n=1096) wore accelerometers for 8
      consecutive days and 774 participants (427 girls, 357 boys) met inclusion
      criteria. PRIMARY AND SECONDARY OUTCOME MEASURES: Total PA (counts per minute,
      cpm); time spent sedentary and in moderate-to-vigorous PA (MVPA); proportion of
      children with >=60 min MVPA on each day of wear (daily approach); proportion of
      children with >=60 min of MVPA on average across days of wear (average approach)
      presented across boys and girls, index of multiple deprivation and season.
      RESULTS: Mean PA level was 648 cpm (95% CI, 627 to 670). Children spent 7.5 hours
      (7.4-7.6) sedentary/day and 72.6 min (70.0-75.3) in MVPA/day. 11% (daily) and 68%
      (average) of children achieved the recommended levels of PA (P<0.05 for
      difference); a greater proportion of boys met the guidelines (12.5% vs 9.8%, NS;
      75.9% vs 59.5%, P<0.001); guideline prevalence exhibited seasonal variation. No
      significant socioeconomic patterning existed across any outcome measure.
      CONCLUSIONS: PA estimates are significantly influenced by the analytical method
      used to assess prevalence. This could have a substantial impact on the evaluation
      of interventions, policy objectives and public health investment. Existing
      guidelines, which focus on daily PA only may not further our understandings about
      the underlying construct itself. Gender differences exist within this age-group,
      suggesting greater investment, with particular consideration of seasonality, is
      needed for targeted intervention work in younger children.

PMID- 29371273
TI  - Management and Point-of-Care for Tobacco Dependence (PROMPT): a feasibility mixed
      methods community-based participatory action research project in Ottawa, Canada.
AB  - OBJECTIVE: To determine the feasibility of a Community-Based Participatory
      Tobacco Dependence Strategy (PROMPT) in the inner city population of Ottawa
      (Canada). DESIGN: A feasibility mixed methods prospective cohort study following
      principles of community-based participatory action research. INTERVENTION:
      Recruited 80 people whouse drugs, followed them for 6 months while providing
      access to counselling, nicotine replacement therapy and peer-support in a
      community setting. SETTING: Community research office in downtown Ottawa,
      adjacent to low-income housing, shelter services and street-based drug
      consumption. PRIMARY OUTCOME: Retention rate at 6-month follow-up. SECONDARY
      OUTCOME: Biochemically validated 7-day point prevalence smoking abstinence at 26
      weeks, self-reported abstinence in the past 7 days with exhaled carbon monoxide
      <=10 ppm. RESULTS: The average age of participants was 43.8 years. The 6-month
      follow-up rate was 42.5%. The mean number of smoking years reported was 27.3
      years. The participants were 70% male, 33.7% reported less than a high-school
      education, 21% identified as indigenous and 43.8% reported an income between
      US$1000 and US$1999 per month. The baseline mean daily cigarette use was 20.5 and
      9.3 cigarettes at study end, with mean reduction of 11.2 cigarettes at 6 months
      (P=0.0001). There was a considerable reduction in self-reported illicit substance
      use (18.8%), including a reduction in the opioids heroin (6.3%), fentanyl (2.6%)
      and Oxycontin (3.8%). The study findings also reveal psycho-socioeconomic
      benefits such as improved health, return to work and greater community
      engagement. CONCLUSIONS: The PROMPT project describes socioeconomic variables
      associated with tobacco and polysubstance use. A programme focused on tobacco
      dependence, easily accessible in the community and led by community peers with
      lived experience is feasible to implement and has the potential to support
      positive life changes. PROMPT's patient engagement model is an effective harm
      reduction strategy for the growing opioid use crisis and can improve the health
      outcomes of marginalised at-risk populations worldwide.

PMID- 29371274
TI  - Role of organisational factors on the 'weekend effect' in critically ill patients
      in Brazil: a retrospective cohort analysis.
AB  - INTRODUCTION: Higher mortality for patients admitted to intensive care units
      (ICUs) during the weekends has been occasionally reported with conflicting
      results that could be related to organisational factors. We investigated the
      effects of ICU organisational and staffing patterns on the potential association
      between weekend admission and outcomes in critically ill patients. METHODS: We
      included 59 614 patients admitted to 78 ICUs participating during 2013. We
      defined 'weekend admission' as any ICU admission from Friday 19:00 until Monday
      07:00. We assessed the association between weekend admission with hospital
      mortality using a mixed logistic regression model controlling for both patient
      level (illness severity, age, comorbidities, performance status and admission
      type) and ICU-level (decrease in nurse/bed ratio on weekend, full-time
      intensivist coverage, use of checklists on weekends and number of institutional
      protocols) confounders. We performed secondary analyses in the subgroup of
      scheduled surgical admissions. RESULTS: A total of 41 894 patients (70.3%) were
      admitted on weekdays and 17 720 patients (29.7%) on weekends. In univariable
      analysis, weekend admitted patients had higher ICU (10.9% vs 9.0%, P<0.001) and
      hospital (16.5% vs 13.5%, P<0.001) mortality. After adjusting for confounders,
      weekend admission was not associated with higher hospital mortality (OR 1.05, 95%
      CI 0.99 to 1.12, P=0.095). However, a 'weekend effect' was still observed in
      scheduled surgical admissions, as well as in ICUs not using checklists during the
      weekends. For unscheduled admissions, no 'weekend effect' was observed regardless
      of ICU's characteristics. For scheduled surgical admissions, a 'weekend effect'
      was present only in ICUs with a low number of implemented protocols and those
      with a reduction in the nurse/bed ratio and not applying checklists during
      weekends. CONCLUSIONS: ICU organisational factors, such as decreased nurse-to
      patient ratio, absence of checklists and fewer standardised protocols, may
      explain, in part, increases in mortality in patients admitted to the ICU
      mortality on weekends.

PMID- 29371275
TI  - Effect of a health literacy intervention trial on knowledge about cardiovascular
      disease medications among Indigenous peoples in Australia, Canada and New
      Zealand.
AB  - OBJECTIVES: To assess the effect of a customised, structured cardiovascular
      disease (CVD) medication health literacy programme on medication knowledge among
      Indigenous people with, or at high risk of, CVD. DESIGN: Intervention trial with
      premeasures and postmeasures at multiple time points. SETTING: Indigenous primary
      care services in Australia, Canada and New Zealand. PARTICIPANTS: 171 Indigenous
      people aged >=20 years of age who had at least one clinical diagnosis of a CVD
      event, or in Canada and Australia had a 5-year CVD risk >=15%, and were
      prescribed at least two of the following CVD medication classes: statin, aspirin,
      ACE inhibitors and beta blockers. INTERVENTION: An education session delivered on
      three occasions over 1 month by registered nurses or health educators who had
      received training in health literacy and principles of adult education. An
      interactive tablet application was used during each session and an information
      booklet and pill card provided to participants. PRIMARY OUTCOME MEASURES:
      Knowledge about the CVD medications assessed before and after each session.
      RESULTS: Knowledge at baseline (presession 1) was low, with the mean per cent
      correct answers highest for statins (34.0% correct answers), 29.4% for aspirin,
      26.0% for beta blockers and 22.7% for ACE inhibitors. Adjusted analyses showed
      highly significant (P<0.001) increases in knowledge scores between preassessments
      and postassessments at all three time points for all medication classes. For the
      four medications, the absolute increases in adjusted per cent correct items from
      presession 1 to postsession 3 assessments were 60.1% for statins, 76.8% for
      aspirin, 71.4% for ACE inhibitor and 69.5% for beta blocker. CONCLUSIONS: The
      intervention was highly effective in contextually diverse Indigenous primary
      healthcare services in Australia, Canada and New Zealand. The findings from this
      study have important implications for health services working with populations
      with low health literacy more generally. TRIAL REGISTRATION NUMBER:
      ACTRN12612001309875.

PMID- 29371276
TI  - Are risk factors for preterm and early-term live singleton birth the same? A
      population-based study in France.
AB  - OBJECTIVES: To investigate whether risk factors for preterm (<37 weeks gestation)
      and early-term birth (37 and 38 weeks gestation) are similar. DESIGN: Nationally
      representative cross-sectional study of births. SETTING: France in 2010.
      PARTICIPANTS: Live singleton births (n=14 326). PRIMARY AND SECONDARY OUTCOME
      MEASURES: Preterm and early-term birth rates overall and by mode of delivery
      (spontaneous and indicated). Risk factors were maternal sociodemographic
      characteristics, previous preterm birth, height, prepregnancy body mass index
      (BMI) and smoking, assessed using multinomial regression models with full-term
      births 39 weeks and over as the reference group. RESULTS: There were 5.5% preterm
      and 22.5% early-term births. Common risk factors were: a previous preterm
      delivery (adjusted relative risk ratio (aRRR) 8.2 (95% CI 6.2 to 10.7) and aRRR
      2.4 (95% CI 2.0 to 3.0), respectively), short stature, underweight (overall and
      in spontaneous deliveries), obesity (in indicated deliveries only), a low
      educational level and Sub-Saharan African origin. In contrast, primiparity was a
      risk factor only for preterm birth, aRRR 1.8 (95% CI 1.5 to 2.2), while higher
      parity was associated with greater risk of early-term birth. CONCLUSIONS: Most
      population-level risk factors were common to both preterm and early-term birth
      with the exception of primiparity, and BMI which differed by mode of onset of
      delivery. Our results suggest that preterm and early-term birth share similar
      aetiologies and thus potentially common strategies for prevention.

PMID- 29371278
TI  - Association between body mass index and obesity-related cancer risk in men and
      women with type 2 diabetes in primary care in the Netherlands: a cohort study
      (ZODIAC-56).
AB  - OBJECTIVE: To investigate the relationship between body mass index (BMI) and
      obesity-related cancers in men and women with type 2 diabetes (T2D). DESIGN:
      Observational cohort study. SETTING: Primary care. PARTICIPANTS: A total of 52
      044 patients with T2D who participated in the ZODIAC (Zwolle Outpatient Diabetes
      project Integrating Available Care) study between 1998 and 2012 was included (49%
      women). A dataset of these patients was linked to available information of the
      Netherlands Cancer Registry to obtain data on cancer incidents. PRIMARY OUTCOME
      MEASURES: Analyses were performed for the total group of obesity-related cancers
      and for non-sex-specific and sex-specific obesity-related cancers (in men:
      advanced prostate cancer, in women: ovarian, endometrial and postmenopausal
      breast cancer). RESULTS: The median follow-up period in all analyses was 3.1 (1.7
      5.0) years in men and 3.1 (1.7-5.1) in women. During follow-up, 689 men and 914
      women were diagnosed with an obesity-related cancer. In men, BMI was associated
      with a higher risk of the total group of obesity-related cancers and non-sex
      specific obesity-related cancers (HR (per 5 kg/m2 increase) 1.12 (95% CI 1.02 to
      1.23) and HR 1.18 (95% CI 1.06 to 1.31)). No association was found with prostate
      cancer. In women, an association between BMI and all obesity-related cancers
      combined and sex-specific obesity-related cancers was present (HR 1.15 (95% CI
      1.08 to 1.22) and HR 1.22 (95% CI 1.14 to 1.32)). No association with non-sex
      specific cancers was found in women. CONCLUSIONS: BMI is associated with obesity
      related cancers in men with T2D, except with advanced prostate cancer. The
      results of this study provide reason to reconsider the classification of advanced
      prostate cancer as an obesity-related cancer, at least in T2D. In women, BMI is
      associated with the total group of obesity-related cancers and with sex-specific
      obesity-related cancers.

PMID- 29371277
TI  - Association between low bone mineral density and hearing impairment in
      postmenopausal women: the Korean National Health and Nutrition Examination
      Survey.
AB  - OBJECTIVE: To investigate the relationship between bone mineral density (BMD) and
      hearing impairment using a nationally demonstrative sample of Korean female
      adults. STUDY DESIGN: Cross-sectional study of a national health survey. METHODS:
      Data from the 2009-2010 Korean National Health and Nutrition Examination Surveys
      (KNHANES) with 19 491 participants were analysed, and 8773 of these participants
      were enrolled in this study. BMD was measured using dual-energy X-ray
      absorptiometry. Auditory functioning was evaluated by pure-tone audiometric
      testing according to established KNHANES protocols. We deliberated auditory
      impairment as pure-tone averages at frequencies of 0.5, 1.0, 2.0 and 3.0 kHz at a
      threshold of >=40 decibels hearing level in the auricle with better hearing
      status. RESULTS: Among women aged 19 years and older, prevalences of bilateral
      hearing impairment in premenopausal and postmenopausal women were 0.1%+/-0.1% and
      11.5%+/-1.1% (mean+/-SE), respectively. Hearing impairment was meaningfully
      associated with low BMD in postmenopausal women. Logistic regression models
      indicated that lower BMDs of the total femur (OR=0.779; 95% CI 0.641 to 0.946,
      P=0.0118) and femur neck (OR=0.746; 95% CI 0.576 to 0.966, P=0.0265) were
      significantly associated with hearing impairment among postmenopausal women.
      CONCLUSIONS: Postmenopausal Korean women with low BMD of the total femur and
      femoral neck showed an increased risk for developing hearing impairment. Further
      epidemiological and investigational studies are needed to elucidate this
      association.

PMID- 29371279
TI  - Manual therapy for unsettled, distressed and excessively crying infants: a
      systematic review and meta-analyses.
AB  - OBJECTIVE: To conduct a systematic review and meta-analyses to assess the effect
      of manual therapy interventions for healthy but unsettled, distressed and
      excessively crying infants and to provide information to help clinicians and
      parents inform decisions about care. METHODS: We reviewed published peer-reviewed
      primary research articles in the last 26 years from nine databases (Medline Ovid,
      Embase, Web of Science, Physiotherapy Evidence Database, Osteopathic Medicine
      Digital Repository , Cochrane (all databases), Index of Chiropractic Literature,
      Open Access Theses and Dissertations and Cumulative Index to Nursing and Allied
      Health Literature). Our inclusion criteria were: manual therapy (by regulated or
      registered professionals) of unsettled, distressed and excessively crying infants
      who were otherwise healthy and treated in a primary care setting. Outcomes of
      interest were: crying, feeding, sleep, parent-child relations, parent
      experience/satisfaction and parent-reported global change. RESULTS: Nineteen
      studies were selected for full review: seven randomised controlled trials, seven
      case series, three cohort studies, one service evaluation study and one
      qualitative study.We found moderate strength evidence for the effectiveness of
      manual therapy on: reduction in crying time (favourable: -1.27 hours per day (95%
      CI -2.19 to -0.36)), sleep (inconclusive), parent-child relations (inconclusive)
      and global improvement (no effect). The risk of reported adverse events was low:
      seven non-serious events per 1000 infants exposed to manual therapy (n=1308) and
      110 per 1000 in those not exposed. CONCLUSIONS: Some small benefits were found,
      but whether these are meaningful to parents remains unclear as does the
      mechanisms of action. Manual therapy appears relatively safe. PROSPERO
      REGISTRATION NUMBER: CRD42016037353.

PMID- 29371280
TI  - Use of primary care and other healthcare services between age 85 and 90 years:
      longitudinal analysis of a single-year birth cohort, the Newcastle 85+ study.
AB  - OBJECTIVE: To describe, using data from the Newcastle 85+ cohort study, the use
      of primary care and other healthcare services by 85-year-olds as they age.
      DESIGN: Longitudinal population-based cohort study. SETTING: Newcastle on Tyne
      and North Tyneside, UK. PARTICIPANTS: Community dwelling and institutionalised
      men and women recruited through general practices (n=845, 319 men and 526 women).
      RESULTS: Contact was established with 97% (n=1409/1459) of eligible 85-year-olds,
      consent obtained from 74% (n=1042/1409) and 851 agreed to undergo the
      multidimensional health assessment and a general practice medical records review.
      A total of 845 participants had complete data at baseline for this study (319
      male, 526 female), with 344 (118 male, 226 female) reinterviewed at 60 months.
      After adjusting for confounders, all consultations significantly increased over
      the 5 years (incidence rate ratio, IRR=1.03, 95% CI 1.01 to 1.05, P=0.001) as did
      general practitioner (GP) consultations (IRR=1.03, 95% CI 1.01 to 1.05, P=0.006).
      Significant increases were also observed in inpatient and day hospital use over
      time, though these disappeared after adjustment for confounders. CONCLUSIONS: Our
      study of primary, secondary and community care use by the very old reveals that,
      between the ages of 85 and 90 years, older people are much more likely to consult
      their GP than any other primary healthcare team members. With a rapidly ageing
      society, it is essential that both current and future GPs are appropriately
      skilled, and adequately supported by specialist colleagues, as the main
      healthcare provider for a population with complex and challenging needs.

PMID- 29371281
TI  - Motives for sickness presence among students at secondary school: a cross
      sectional study in five European countries.
AB  - OBJECTIVES: This article investigates various motives for sickness presence (SP)
      among students in secondary school. DESIGN: Cross-sectional study. SETTING: 25
      secondary schools in Belgium, Estonia, Finland, Italy and Latvia. PARTICIPANTS:
      5002 students between 16 and 19 years of age, 49% female. RESULTS: Almost half of
      the students reported two or more incidents of SP. The study indicated that the
      practice of SP was mainly extrinsically motivated. The most often reported
      motives for SP were that absence could affect grades negatively, that important
      curriculum material was explained at the school and attendance requirements. Some
      students practising SP expressed intrinsic motivation, such as maintaining their
      social network and interest in what was learnt at school. CONCLUSION: The study
      investigated various motives for SP in secondary schools in five European
      countries. Extrinsic motivation for SP was more often reported than intrinsic
      motivation for SP. Multivariate analyses indicated that boys, students in
      vocational education, immigrants and students with low-educated parents more
      often reported intrinsic motivation for SP, while girls and students with high
      absence more often reported extrinsic motivation. There were also notable cross
      country differences regarding reported motives for SP.

PMID- 29371282
TI  - Controlled pre-post, mixed-methods study to determine the effectiveness of a
      national delirium clinical care standard to improve the diagnosis and care of
      patients with delirium in Australian hospitals: a protocol.
AB  - INTRODUCTION: Delirium, an acute confusional state, affects up to 29% of acute
      inpatients aged 65 years and over. The Australian Delirium Clinical Care Standard
      (the Standard) contains evidence-based, multicomponent interventions, to identify
      and reduce delirium. This study aims to: (1) conduct a controlled, before-and
      after study to assess the clinical effectiveness of the Standard to improve
      diagnosis and treatment of delirium; (2) conduct a cost-effectiveness study of
      implementing the Standard and (3) evaluate the implementation process. METHODS
      AND ANALYSIS: The study will use a controlled, preimplementation and
      postimplementation mixed-methods study design, including: medical record reviews,
      activity-based costing analysis and interviews with staff, patients and their
      family members. The study population will comprise patients 65 years and over,
      admitted to surgical, medical and intensive care wards in four intervention
      hospitals and one control hospital. The primary clinical outcome will be the
      incidence of delirium. Secondary outcomes include: length of stay, severity and
      duration of delirium, inhospital mortality rates, readmission rates and use of
      psychotropic drugs. Cost-effectiveness will be evaluated through activity-based
      costing analysis and outcome data, and the implementation process appraised
      through the qualitative results. ETHICS AND DISSEMINATION: Ethics approval has
      been received for two hospitals. Additional hospitals have been identified and
      ethics applications will be submitted once the tools in the pilot study have been
      tested.The results will be submitted for publication in peer-reviewed journals
      and presented to national and international conferences. Results seminars will
      provide a quality feedback mechanism for staff and health policy bodies.

PMID- 29371283
TI  - Clinical features, antimicrobial susceptibility patterns and genomics of bacteria
      causing neonatal sepsis in a children's hospital in Vietnam: protocol for a
      prospective observational study.
AB  - INTRODUCTION: The clinical syndrome of neonatal sepsis, comprising signs of
      infection, septic shock and organ dysfunction in infants <=4 weeks of age, is a
      frequent sequel to bloodstream infection and mandates urgent antimicrobial
      therapy. Bacterial characterisation and antimicrobial susceptibility testing is
      vital for ensuring appropriate therapy, as high rates of antimicrobial resistance
      (AMR), especially in low-income and middle-income countries, may adversely affect
      outcome. Ho Chi Minh City (HCMC) in Vietnam is a rapidly expanding city in
      Southeast Asia with a current population of almost 8 million. There are limited
      contemporary data on the causes of neonatal sepsis in Vietnam, and we hypothesise
      that the emergence of multidrug resistant bacteria is an increasing problem for
      the appropriate management of sepsis cases. In this study, we aim to investigate
      the major causes of neonatal sepsis and assess disease outcomes by clinical
      features, antimicrobial susceptibility profiles and genome composition. METHOD
      AND ANALYSIS: We will conduct a prospective observational study to characterise
      the clinical and microbiological features of neonatal sepsis in a major
      children's hospital in HCMC. All bacteria isolated from blood subjected to whole
      genome sequencing. We will compare clinical variables and outcomes between
      different bacterial species, genome composition and AMR gene content. AMR gene
      content will be assessed and stratified by species, years and contributing
      hospital departments. Genome sequences will be analysed to investigate
      phylogenetic relationships. ETHICS AND DISSEMINATION: The study will be conducted
      in accordance with the principles of the Declaration of Helsinki and the
      International Council on Harmonization Guidelines for Good Clinical Practice.
      Ethics approval has been provided by the Oxford Tropical Research Ethics
      Committee 35-16 and Vietnam Children's Hospital 1 Ethics Committee 73/GCN/BVND1.
      The findings will be disseminated at international conferences and peer-reviewed
      journals. TRIAL REGISTRATION NUMBER: ISRCTN69124914; Pre-results.

PMID- 29371285
TI  - Best practices for community-engaged participatory research with Pacific Islander
      communities in the USA and USAPI: protocol for a scoping review.
AB  - INTRODUCTION: Community-based participatory research is a partnership approach to
      research that seeks to equally involve community members, organisational
      representatives and academic partners throughout the research process in a
      coequal and mutually beneficial partnership. To date, no published article has
      synthesised the best practices for community-based participatory research
      practices with Pacific Islanders. METHODS AND ANALYSIS: The reviewers will
      examine studies' titles, abstracts and full text, comparing eligibility to
      address discrepancies. For each eligible study, data extraction will be executed
      by two reviewers and one confirmation coder, comparing extracted data to address
      any discrepancies. Eligible data will be synthesised and reported in a narrative
      review assessing coverage and gaps in existing literature related to community
      based participatory research with Pacific Islanders. DISCUSSION AND
      DISSEMINATION: The purpose of this review is to identify best practices used when
      conducting community-based participatory research with Pacific Islanders; it will
      also extrapolate where the gaps are in the existing literature. This will be the
      first scoping review on community-based participatory research with Pacific
      Islanders. To facilitate dissemination, the results of this scoping review will
      be submitted for publication to a peer-reviewed journal, presented at conferences
      and shared with community-based participatory research stakeholders.

PMID- 29371284
TI  - Comparative effectiveness of novel oral anticoagulants in UK patients with non
      valvular atrial fibrillation and chronic kidney disease: a matched cohort study.
AB  - OBJECTIVES: To evaluate the effectiveness and safety of novel oral anticoagulants
      (NOACs) compared with vitamin K antagonists (VKAs) among patients with non
      valvular atrial fibrillation (NVAF), particularly those with chronic kidney
      disease (CKD). DESIGN: Population-based matched cohort study. SETTING: Over 670
      primary care practices in the UK, contributing to the Clinical Practice Research
      Datalink. PARTICIPANTS: Up to 6818 adult patients newly treated with NOACs
      between 2011 and 2016, matched 1:1 to new users of VKAs on age, sex and high
      dimensional propensity score. INTERVENTIONS: Current exposure to NOACs compared
      with current exposure to VKAs. MAIN OUTCOME MEASURES: HRs of ischaemic stroke and
      systemic embolism (SE), major bleeding, gastrointestinal (GI) bleeding,
      intracranial bleeding, myocardial infarction and all-cause mortality. RESULTS: In
      as-treated analyses, the rates of ischaemic stroke/SE were similar between NOACs
      and VKAs (HR 0.94; 95% CI 0.62 to 1.42), as were the rates of major bleeding (HR
      0.86; 95% CI 0.56 to 1.33). NOACs also significantly increased the risk of GI
      bleeding (HR 1.78; 95% CI 1.27 to 2.48). In patients with NVAF and CKD, NOACs and
      VKAs remained comparable with respect to the risk of ischaemic stroke/SE (HR
      0.79; 95% CI 0.40 to 1.58) and major bleeding (HR 0.88; 95% CI 0.47 to 1.62),
      with no difference in the risk of GI bleeding (HR 0.99; 95% CI 0.63 to 1.55).
      Similar results were obtained in on-treatment analyses using a time-dependent
      exposure definition. CONCLUSIONS: Our results suggest that in the UK primary
      care, NOACs are overall effective and safe alternatives to VKAs, among patients
      with NVAF altogether, as well as in patients with NVAF and CKD.

PMID- 29371287
TI  - Correction: Prevalence of and factors associated with adopting bone health
      promoting behaviours among people with osteoporosis in Taiwan: a cross-sectional
      study.

PMID- 29371286
TI  - Association of chronic kidney disease with mortality risk in patients with lung
      cancer: a nationwide Taiwan population-based cohort study.
AB  - OBJECTIVE: Our population-based research aimed to clarify the association between
      chronic kidney disease (CKD) and mortality risk in patients with lung cancer.
      DESIGN: Retrospective cohort study SETTING: National health insurance research
      database in Taiwan PARTICIPANTS: All (n=1 37 077) Taiwanese residents who were
      diagnosed with lung cancer between 1997 and 2012 were identified. Eligible
      patients with baseline CKD (n=2269) were matched with controls (1:4, n=9076)
      without renal disease according to age, sex and the index day of lung cancer
      diagnosis. METHODS: The cumulative incidence of death was calculated by the
      Kaplan-Meier method, and the risk determinants were explored by the Cox
      proportional hazards model. RESULTS: Mortality occurred in 1866 (82.24%) and 7135
      (78.61%) patients with and without CKD, respectively (P=0.0001). The cumulative
      incidences of mortality in patients with and without chronic renal disease were
      72.8% vs 61.6% at 1 year, 82.0% vs 76.6% at 2 years and 88.9% vs 87.2% at 5
      years, respectively. After adjusting for multiple confounding factors including
      age and comorbidities, Cox regression analysis revealed that CKD was associated
      with an increased risk of mortality (adjusted HR 1.38; 95% CI 1.29 to 1.47).
      Stratified analysis further showed that the association was consistent across
      patient subgroups. CONCLUSION: Comorbidity associated with CKD is a risk factor
      for mortality in patients with lung cancer.

PMID- 29371288
TI  - Seven days in medicine: 17-23 January 2018.

PMID- 29371290
TI  - Protein Tyrosine Phosphatase Receptor Type G (PTPRG) Controls Fibroblast Growth
      Factor Receptor (FGFR) 1 Activity and Influences Sensitivity to FGFR Kinase
      Inhibitors.
AB  - Recently, FGFR1 was found to be overexpressed in osteosarcoma and represents an
      important target for precision medicine. However, because targeted cancer therapy
      based on FGFR inhibitors has so far been less efficient than expected, a detailed
      understanding of the target is important. We have here applied proximity
      dependent biotin labeling combined with label-free quantitative mass spectrometry
      to identify determinants of FGFR1 activity in an osteosarcoma cell line. Many
      known FGFR interactors were identified (e.g. FRS2, PLCG1, RSK2, SRC), but the
      data also suggested novel determinants. A strong hit in our screen was the
      tyrosine phosphatase PTPRG. We show that PTPRG and FGFR1 interact and colocalize
      at the plasma membrane where PTPRG directly dephosphorylates activated FGFR1. We
      further show that osteosarcoma cell lines depleted for PTPRG display increased
      FGFR activity and are hypersensitive to stimulation by FGF1. In addition, PTPRG
      depletion elevated cell growth and negatively affected the efficacy of FGFR
      kinase inhibitors. Thus, PTPRG may have future clinical relevance by being a
      predictor of outcome after FGFR inhibitor treatment.

PMID- 29371292
TI  - Excess of Love.

PMID- 29371289
TI  - Elevated vasopressin in pregnant mice induces T-helper subset alterations
      consistent with human preeclampsia.
AB  - The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy,
      involves imbalanced T helper (TH) cell populations and resultant changes in pro-
      and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of
      arginine vasopressin (AVP)), secretion precedes the development of symptoms in
      PreE in humans, and infusion of AVP proximal to and throughout gestation is
      sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type
      C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient
      to induce the immune changes observed in human PreE. AVP infusion throughout
      gestation in mice resulted in increased pro-inflammatory interferon gamma (IFNg)
      (TH1) in the maternal plasma. The TH17-associated cytokine interleukin (IL)-17
      was elevated in the maternal plasma, amniotic fluid, and placenta following AVP
      infusion. Conversely, the TH2-associated anti-inflammatory cytokine IL-4 was
      decreased in the maternal and fetal kidneys from AVP-infused dams, while IL-10
      was decreased in the maternal kidney and all fetal tissues. Collectively, these
      results demonstrate the sufficiency of AVP to induce the immune changes typical
      of PreE. We investigated if T cells can respond directly to AVP by evaluating the
      expression of AVP receptors (AVPRs) on mouse and human CD4+ T cells. Mouse and
      human T cells expressed AVPR1a, AVPR1b, and AVPR2. The expression of AVPR1a was
      decreased in CD4+ T cells obtained from PreE-affected women. In total, our data
      are consistent with a potential initiating role for AVP in the immune dysfunction
      typical of PreE and identifies putative signaling mechanism(s) for future
      investigation.

PMID- 29371291
TI  - Multiomics Integration Reveals the Landscape of Prometastasis Metabolism in
      Hepatocellular Carcinoma.
AB  - The systematic investigation of gene mutation and expression is important to
      discover novel biomarkers and therapeutic targets in cancers. Here, we integrated
      genomics, transcriptomics, proteomics, and metabolomics to analyze three
      hepatocellular carcinoma (HCC) cell lines with differential metastatic
      potentials. The results revealed the profile of the prometastasis metabolism
      potentially associated with HCC metastasis. The multiomic analysis identified 12
      genes with variations at multiple levels from three metabolic pathways, including
      glycolysis, starch, and sucrose metabolism, and glutathione metabolism.
      Furthermore, uridine diphosphate (UDP)-glucose pyrophosphorylase 2 (UGP2), was
      observed to be persistently up-regulated with increased metastatic potential.
      UGP2 overexpression promoted cell migration and invasion and enhanced
      glycogenesis in vitro The role of UGP2 in metastasis was further confirmed using
      a tumor xenograft mouse model. Taken together, the compendium of multiomic data
      provides valuable insights in understanding the roles of shifted cellular
      metabolism in HCC metastasis.

PMID- 29371293
TI  - Organ donation: a national consultation.

PMID- 29371294
TI  - Organ donation: opting in or opting out?

PMID- 29371295
TI  - Stemming the tide of antimicrobial resistance: implications for management of
      acne vulgaris.

PMID- 29371296
TI  - Skill-mix change and the general practice workforce challenge.

PMID- 29371297
TI  - Personalised medicine in general practice: the example of raised cholesterol.

PMID- 29371298
TI  - Type 1 self-diagnosis.

PMID- 29371299
TI  - A positive diagnosis of irritable bowel syndrome does not give immunity from
      developing bowel cancer.

PMID- 29371300
TI  - Patients' acceptance of physician associates.

PMID- 29371301
TI  - Bad medicine.

PMID- 29371302
TI  - Viewpoint: Resilience training, really?

PMID- 29371303
TI  - Child sexual exploitation in Coronation Street.

PMID- 29371304
TI  - GPs and green socks: don't get stuck between a sock and a hard place.

PMID- 29371305
TI  - Premature ovarian insufficiency: why is it not being diagnosed enough in primary
      care?

PMID- 29371306
TI  - Yonder: Sleep quality, febrile seizures, interpreters, and doulas.

PMID- 29371307
TI  - Clinical pharmacists in general practice: a necessity not a luxury?

PMID- 29371308
TI  - An embarrassing handicap.

PMID- 29371309
TI  - Bad Medicine: Letters.

PMID- 29371310
TI  - Books: Righteous Dopefiend: An Ethnography of Homeless Heroin Users.

PMID- 29371311
TI  - Books: How Doctors Think: Clinical Judgment and the Practice of Medicine: The
      Importance of Anecdote.

PMID- 29371312
TI  - Child health.

PMID- 29371313
TI  - Childhood obesity: a challenge for primary care teams.

PMID- 29371314
TI  - Vaccinations not covered under Section 7a: who pays?

PMID- 29371315
TI  - Should we be screening for thyroid dysfunction in patients with type 2 diabetes
      mellitus?

PMID- 29371316
TI  - The management of lupus in young people.

PMID- 29371317
TI  - Management of nut allergy in primary care.

PMID- 29371318
TI  - Adaptive History Biases Result from Confidence-weighted Accumulation of Past
      Choices.
AB  - Perceptual decision-making is biased by previous events, including the history of
      preceding choices: Observers tend to repeat (or alternate) their judgments of the
      sensory environment more often than expected by chance. Computational models
      postulate that these so-called choice history biases result from the accumulation
      of internal decision signals across trials. Here, we provide psychophysical
      evidence for such a mechanism and its adaptive utility. Male and female human
      observers performed different variants of a challenging visual motion
      discrimination task near psychophysical threshold. In a first experiment, we
      decoupled categorical perceptual choices and motor responses on a trial-by-trial
      basis. Choice history bias was explained by previous perceptual choices, not
      motor responses, highlighting the importance of internal decision signals in
      action-independent formats. In a second experiment, observers performed the task
      in stimulus environments containing different levels of auto-correlation and
      providing no external feedback about choice correctness. Despite performing under
      overall high levels of uncertainty, observers adjusted both the strength and the
      sign of their choice history biases to these environments. When stimulus
      sequences were dominated by either repetitions or alternations, the individual
      degree of this adjustment of history bias was about as good a predictor of
      individual performance as individual perceptual sensitivity. The history bias
      adjustment scaled with two proxies for observers' confidence about their previous
      choices (accuracy and reaction time). Taken together, our results are consistent
      with the idea that action-independent, confidence-modulated decision variables
      are accumulated across choices in a flexible manner that depends on decision
      makers' model of their environment.Significance statement:Decisions based on
      sensory input are often influenced by the history of one's preceding choices,
      manifesting as a bias to systematically repeat (or alternate) choices. We here
      provide support for the idea that such choice history biases arise from the
      context-dependent accumulation of a quantity referred to as the decision
      variable: the variable's sign dictates the choice and its magnitude the
      confidence about choice correctness. We show that choices are accumulated in an
      action-independent format and a context-dependent manner, weighted by the
      confidence about their correctness. This confidence-weighted accumulation of
      choices enables decision-makers to flexibly adjust their behavior to different
      sensory environments. The bias adjustment can be as important for optimizing
      performance as one's sensitivity to the momentary sensory input.

PMID- 29371319
TI  - Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in
      ChAT-Cre Mouse Lines.
AB  - The recent development of transgenic rodent lines expressing cre recombinase in a
      cell-specific manner, along with advances in engineered viral vectors, has
      permitted in-depth investigations into circuit function. However, emerging
      evidence has begun to suggest that genetic modifications may introduce unexpected
      caveats. In the current studies, we sought to extensively characterize male and
      female mice from both the ChAT(BAC)-Cre mouse line, created with the bacterial
      artificial chromosome (BAC) method, and ChAT(IRES)-Cre mouse line, generated with
      the internal ribosome entry site (IRES) method. ChAT(BAC)-Cre transgenic and wild
      type mice did not differ in general locomotor behavior, anxiety measures, drug
      induced cataplexy, nicotine-mediated hypolocomotion, or operant food training.
      However, ChAT(BAC)-Cre transgenic mice did exhibit significant deficits in
      intravenous nicotine self-administration, which paralleled an increase in
      vesicular acetylcholine transporter and choline acetyltransferase (ChAT)
      hippocampal expression. For the ChAT(IRES)-Cre line, transgenic mice exhibited
      deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant
      food training compared with wild-type and hemizygous littermates. No differences
      among ChAT(IRES)-Cre wild-type, hemizygous, and transgenic littermates were found
      in anxiety measures, drug-induced cataplexy, and nicotine self-administration.
      Given that increased cre expression was present in the ChAT(IRES)-Cre transgenic
      mice, as well as a decrease in ChAT expression in the hippocampus, altered
      neuronal function may underlie behavioral phenotypes. In contrast, ChAT(IRES)-Cre
      hemizygous mice were more similar to wild-type mice in both protein expression
      and the majority of behavioral assessments. As such, interpretation of data
      derived from ChAT-Cre rodents must consider potential limitations dependent on
      the line and/or genotype used in research investigations.SIGNIFICANCE STATEMENT
      Altered baseline and/or nicotine-mediated behavioral profiles were discovered in
      transgenic mice from the ChAT(BAC)-Cre and ChAT(IRES)-Cre lines. Given that these
      cre-expressing mice have become increasingly used by the scientific community,
      either independently with chemicogenetic and optogenetic viral vectors or crossed
      with other transgenic lines, the current studies highlight important
      considerations for the interpretation of data from previous and future
      experimental investigations. Moreover, the current findings detail the behavioral
      effects of either increased or decreased baseline cholinergic signaling
      mechanisms on locomotor, anxiety, learning/memory, and intravenous nicotine self
      administration behaviors.

PMID- 29371320
TI  - Antagonistic Interactions Between Microsaccades and Evidence Accumulation
      Processes During Decision Formation.
AB  - Despite their small size, microsaccades can impede stimulus detections if
      executed at inopportune times. Although it has been shown that microsaccades
      evoke both inhibitory and excitatory responses across different visual regions,
      their impact on the higher-level neural decision processes that bridge sensory
      responses to action selection has yet to be examined. Here, we show that when
      human observers monitor stimuli for subtle feature changes, the occurrence of
      microsaccades long after (up to 800 ms) change onset predicts slower reaction
      times and this is accounted for by momentary suppression of neural signals at
      each key stage of decision formation: visual evidence encoding, evidence
      accumulation, and motor preparation. Our data further reveal that, independent of
      the timing of the change events, the onset of neural decision formation coincides
      with a systematic inhibition of microsaccade production, persisting until the
      perceptual report is executed. Our combined behavioral and neural measures
      highlight antagonistic interactions between microsaccade occurrence and evidence
      accumulation during visual decision-making tasks.SIGNIFICANCE STATEMENT When
      fixating on a location in space, we frequently make tiny eye movements called
      microsaccades. In the present study, we show that these microsaccades impede our
      ability to make perceptual decisions about visual stimuli and this impediment
      specifically occurs via the disruption of several processing levels of the
      sensorimotor network: the encoding of visual evidence itself, the accumulation of
      visual evidence toward a response, and effector-selective motor preparation.
      Furthermore, we show that the production of microsaccades is inhibited during the
      perceptual decision, possibly as a counteractive measure to mitigate their
      negative effect on behavior in this context. The combined behavioral and neural
      measures used in this study provide strong and novel evidence for the interaction
      of fixational eye movements and the perceptual decision-making process.

PMID- 29371322
TI  - Iron overload in transfusion-dependent survivors of hemoglobin Bart's hydrops
      fetalis.

PMID- 29371321
TI  - Role of Anterior Intralaminar Nuclei of Thalamus Projections to Dorsomedial
      Striatum in Incubation of Methamphetamine Craving.
AB  - Relapse to methamphetamine (Meth) seeking progressively increases after
      withdrawal from drug self-administration (incubation of Meth craving). We
      previously demonstrated a role of dorsomedial striatum (DMS) dopamine D1
      receptors (D1Rs) in this incubation. Here, we studied the role of afferent
      glutamatergic projections into the DMS and local D1R-glutamate interaction in
      this incubation in male rats. We first measured projection-specific activation on
      day 30 relapse test by using cholera toxin b (retrograde tracer) + Fos (activity
      marker) double-labeling in projection areas. Next, we determined the effect of
      pharmacological reversible inactivation of lateral or medial anterior
      intralaminar nuclei of thalamus (AIT-L or AIT-M) on incubated Meth seeking on
      withdrawal day 30. We then used an anatomical asymmetrical disconnection
      procedure to determine whether an interaction between AIT-L->DMS glutamatergic
      projections and postsynaptic DMS D1Rs contributes to incubated Meth seeking. We
      also determined the effect of unilateral inactivation of AIT-L and D1R blockade
      of DMS on incubated Meth seeking, and the effect of contralateral disconnection
      of AIT-L->DMS projections on nonincubated Meth seeking on withdrawal day 1.
      Incubated Meth seeking was associated with selective activation of AIT->DMS
      projections; other glutamatergic projections to DMS were not activated. AIT-L
      (but not AIT-M) inactivation or anatomical disconnection of AIT-L->DMS
      projections decreased incubated Meth seeking. Unilateral inactivation of AIT-L or
      D1R blockade of the DMS had no effect on incubated Meth craving, and
      contralateral disconnection of AIT-L->DMS projections had no effect on
      nonincubated Meth seeking. Our results identify a novel role of AIT-L and AIT-L
      >DMS glutamatergic projections in incubation of drug craving and drug
      seeking.SIGNIFICANCE STATEMENT Methamphetamine seeking progressively increases
      after withdrawal from drug self-administration, a phenomenon termed incubation of
      methamphetamine craving. We previously found that D1R-mediated dopamine
      transmission in the dorsomedial striatum plays a critical role in this incubation
      phenomenon. Here, we used neuroanatomical and neuropharmacological methods in
      rats to demonstrate that an interaction between the glutamatergic projection from
      the lateral anterior intralaminar nuclei of the thalamus to the dorsomedial
      striatum and local dopamine D1 receptors plays a critical role in relapse to
      methamphetamine seeking after prolonged withdrawal. Our study identified a novel
      motivation-related thalamostriatal projection critical to relapse to drug
      seeking.

PMID- 29371323
TI  - IGHV segment utilization in immunoglobulin gene rearrangement differentiates
      patients with anti-myelin-associated glycoprotein neuropathy from others
      immunoglobulin M-gammopathies.

PMID- 29371324
TI  - Outcomes of patients with relapsed aggressive adult T-cell leukemia-lymphoma:
      clinical effectiveness of anti-CCR4 antibody and allogeneic hematopoietic stem
      cell transplantation.

PMID- 29371325
TI  - A three-year prospective study of the presentation and clinical outcomes of major
      bleeding episodes associated with oral anticoagulant use in the UK (ORANGE
      study).
AB  - The outcomes of patients developing major bleeding while on oral anticoagulants
      remain largely unquantified. The objectives of this study were to: (i) describe
      the burden of major hemorrhage associated with all available oral anticoagulants
      in terms of proportion of bleeds which are intracranial hemorrhages, in-hospital
      mortality and duration of hospitalization following major bleeding; (ii) identify
      risk factors for mortality; and (iii) compare the characteristics of major
      hemorrhage between cases treated with warfarin and direct oral anticoagulants for
      the subgroups of patients with atrial fibrillation or venous thromboembolism.
      This was a multicenter, 3-year prospective cohort study of patients aged >=18
      years on oral anticoagulants who developed major hemorrhage leading to
      hospitalization. The patients were followed up for 30 days or until discharge or
      death, whichever occurred first. In total 2,192 patients (47% female, 81% on
      warfarin, median age 80 years) were reported between October 2013 and August 2016
      from 32 hospitals in the UK. Bleeding sites were intracranial (44%),
      gastrointestinal (33%), and other (24%). The in-hospital mortality was 21% (95%
      CI: 19%-23%) overall, and 33% (95% CI: 30%-36%) for patients with intracranial
      hemorrhage. Intracranial hemorrhage, advanced age, spontaneous bleeding, liver
      failure and cancer were risk factors for death. Compared to warfarin-treated
      patients, patients treated with direct oral anticoagulants were older and had
      lower odds of subdural/epidural, subarachnoid and intracerebral bleeding. The
      mortality rate due to major bleeding was not different between patients being
      treated with warfarin or direct oral anticoagulants. Major bleeding while on oral
      anticoagulant therapy leads to considerable hospital stays and short-term
      mortality.

PMID- 29371326
TI  - Leptin-deficient obesity prolongs survival in a murine model of myelodysplastic
      syndrome.
AB  - Obesity enhances the risk of developing myelodysplastic syndromes. However, the
      effect of obesity on survival is unclear. Obese people present with monocytosis
      due to inflammatory signals emanating from obese adipose tissue. We hypothesized
      that obesity-induced myelopoiesis would promote the transition of myelodysplastic
      syndrome to acute myeloid leukemia and accelerate mortality in obesity. Obese
      Ob/Ob mice or their lean littermate controls received a bone marrow transplant
      from NUP98-HOXD13 transgenic mice, a model of myelodysplastic syndrome. The
      metabolic parameters of the mice were examined throughout the course of the
      study, as were blood leukocytes. Myeloid cells were analyzed in the bone, spleen,
      liver and adipose tissue by flow cytometry halfway through the disease
      progression and at the endpoint. Survival curves were also calculated. Contrary
      to our hypothesis, transplantation of NUP98-HOXD13 bone marrow into obese
      recipient mice significantly increased survival time compared with lean recipient
      controls. While monocyte skewing was exacerbated in obese mice receiving NUP98
      HOXD13 bone marrow, transformation to acute myeloid leukemia was not enhanced.
      Increased survival of obese mice was associated with a preservation of fat mass
      as well as increased myeloid cell deposition within the adipose tissue, and a
      concomitant reduction in detrimental myeloid cell accumulation within other
      organs. The study herein revealed that obesity increases survival in animals with
      myelodysplastic syndrome. This may be due to the greater fat mass of Ob/Ob mice,
      which acts as a sink for myeloid cells, preventing their accumulation in other
      key organs, such as the liver.

PMID- 29371328
TI  - Role of combined prenatal and postnatal paracetamol exposure on asthma
      development: the Czech ELSPAC study.
AB  - BACKGROUND: Prenatal and postnatal paracetamol exposure has been previously
      associated with asthma development in childhood in Western populations. We
      explore the association between prenatal and postnatal paracetamol exposure and
      asthma development in a Central European sample of Czech children, suggesting
      possible additive effect of the both exposures. Furthermore, since aspirin had
      been used more widely during study data collection in Central Europe, we also
      compared asthma development for those exposed to paracetamol and aspirin.
      METHODS: We used data from 3329 children born in the 1990s as members of the
      prospective Czech European Longitudinal Study of Pregnancy and Childhood. Data
      about prenatal and postnatal paracetamol and aspirin exposure, and potential
      covariates were obtained from questionnaires completed by mothers. Data about
      incident asthma were obtained from paediatrician health records. RESULTS: 60.9%
      of children received paracetamol only postnatally, 1.5% only prenatally and 4.9%
      of children were exposed both during pregnancy and infancy. Prevalence of asthma
      in following population was 5% at 11 years. Being exposed to paracetamol both in
      prenatal and postnatal period was associated with asthma development (unadjusted
      OR 1.98, 95% CI 1.02 to 3.87). Being exposed only in the postnatal period was
      also significantly associated with increased risk of asthma. No association
      between prenatal exposure only and outcome was found. A higher but non
      significant risk of asthma was observed for those whose mothers used paracetamol
      during pregnancy compared with those who used aspirin. CONCLUSIONS: The main
      findings of this prospective birth cohort study add to previous observations
      linking prenatal and early postnatal paracetamol exposure to asthma development.
      However, the magnitude of effect is relatively modest, and therefore, we
      recommend paracetamol to remain the analgesic and antipyretic of choice
      throughout pregnancy and early childhood.

PMID- 29371327
TI  - Knockdown of the mitochondria-localized protein p13 protects against experimental
      parkinsonism.
AB  - Mitochondrial dysfunction in the nigrostriatal dopaminergic system is a critical
      hallmark of Parkinson's disease (PD). Mitochondrial toxins produce cellular and
      behavioural dysfunctions resembling those in patients with PD Causative gene
      products for familial PD play important roles in mitochondrial function.
      Therefore, targeting proteins that regulate mitochondrial integrity could provide
      convincing strategies for PD therapeutics. We have recently identified a novel 13
      kDa protein (p13) that may be involved in mitochondrial oxidative
      phosphorylation. In the current study, we examine the mitochondrial function of
      p13 and its involvement in PD pathogenesis using mitochondrial toxin-induced PD
      models. We show that p13 overexpression induces mitochondrial dysfunction and
      apoptosis. p13 knockdown attenuates toxin-induced mitochondrial dysfunction and
      apoptosis in dopaminergic SH-SY5Y cells via the regulation of complex I.
      Importantly, we generate p13-deficient mice using the CRISPR/Cas9 system and
      observe that heterozygous p13 knockout prevents toxin-induced motor deficits and
      the loss of dopaminergic neurons in the substantia nigra. Taken together, our
      results suggest that manipulating p13 expression may be a promising avenue for
      therapeutic intervention in PD.

PMID- 29371330
TI  - Treatment of refractory thyroid cancer.
AB  - Distant metastases from thyroid cancer of follicular origin are uncommon.
      Treatment includes levothyroxine administration, focal treatment modalities with
      surgery, external radiation therapy and thermal ablation, and radioiodine in
      patients with uptake of 131I in their metastases. Two-thirds of distant
      metastases become refractory to radioiodine at some point, and when there is a
      significant tumor burden and documented progression on imaging, a treatment with
      a kinase inhibitor may provide benefits.

PMID- 29371329
TI  - Development of new preclinical models to advance adrenocortical carcinoma
      research.
AB  - Adrenocortical cancer (ACC) is an orphan malignancy that results in heterogeneous
      clinical phenotypes and molecular genotypes. There are no curative treatments for
      this deadly cancer with 35% survival at five years. Our understanding of the
      underlying pathobiology and our ability to test novel therapeutic targets has
      been limited due to the lack of preclinical models. Here, we report the
      establishment of two new ACC cell lines and corresponding patient-derived
      xenograft (PDX) models. CU-ACC1 cell line and PDX were derived from a perinephric
      metastasis in a patient whose primary tumor secreted aldosterone. CU-ACC2 cell
      line and PDX were derived from a liver metastasis in a patient with Lynch
      syndrome. Short tandem repeat profiling confirmed consistent matches between
      human samples and models. Both exomic and RNA sequencing profiling were performed
      on the patient samples and the models, and hormonal secretion was evaluated in
      the new cell lines. RNA sequencing and immunohistochemistry confirmed the
      expression of adrenal cortex markers in the PDXs and human tumors. The new cell
      lines replicate two of the known genetic models of ACC. CU-ACC1 cells had a
      mutation in CTNNB1 and secreted cortisol but not aldosterone. CU-ACC2 cells had a
      TP53 mutation and loss of MSH2 consistent with the patient's known germline
      mutation causing Lynch syndrome. Both cell lines can be transfected and
      transduced with similar growth rates. These new preclinical models of ACC
      significantly advance the field by allowing investigation of underlying molecular
      mechanisms of ACC and the ability to test patient-specific therapeutic targets.

PMID- 29371331
TI  - HSD17B1 expression induces inflammation-aided rupture of mammary gland
      myoepithelium.
AB  - Hydroxysteroid (17-beta) dehydrogenase type 1 (HSD17B1) converts low-active
      estrogen estrone to highly active estradiol. Estradiol is necessary for normal
      postpubertal mammary gland development; however, elevated estradiol levels
      increase mammary tumorigenesis. To investigate the significance of the human
      HSD17B1 enzyme in the mammary gland, transgenic mice universally overexpressing
      human HSD17B1 were used (HSD17B1TG mice). Mammary glands obtained from HSD17B1TG
      females at different ages were investigated for morphology and histology, and
      HSD17B1 activity and estrogen receptor activation in mammary gland tissue were
      assessed. To study the significance of HSD17B1 enzyme expression locally in
      mammary gland tissue, HSD17B1-expressing mammary epithelium was transplanted into
      cleared mammary fat pads of wild-type females, and the effects on mammary gland
      estradiol production, epithelial cells and the myoepithelium were investigated.
      HSD17B1TG females showed increased estrone to estradiol conversion and estrogen
      response element-driven estrogen receptor signaling in mammary gland tissue, and
      they showed extensive lobuloalveolar development that was further enhanced by age
      along with an increase in serum prolactin concentrations. At old age, HSD17B1TG
      females developed mammary cancers. Mammary-restricted HSD17B1 expression induced
      lesions at the sites of ducts and alveoli, accompanied by peri- and intraductal
      inflammation and disruption of the myoepithelial cell layer. The lesions were
      shown to be estrogen dependent, as treatment with an antiestrogen, ICI 182,780,
      starting when lesions were already established reversed the phenotype. These data
      elucidate the ability of human HSD17B1 to enhance estrogen action in the mammary
      gland in vivo and indicate that HSD17B1 is a factor inducing phenotypic
      alterations associated with mammary tumorigenesis.

PMID- 29371332
TI  - The impact of 27-hydroxycholesterol on endometrial cancer proliferation.
AB  - Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is
      a major risk factor for EC and is associated with elevated cholesterol. 27
      hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an
      endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor
      modulator (SERM). Exposure to oestrogenic ligands increases risk of developing
      EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC (n = 126)
      were collected from postmenopausal women undergoing hysterectomy. Expression of
      LXRs (NR1H3, LXRalpha; NR1H2, LXRbeta) and enzymes required for the synthesis
      (CYP27A1) or breakdown (CYP7B1) of 27HC were detected in all grades of EC. Cell
      lines originating from well-, moderate- and poorly-differentiated ECs (Ishikawa,
      RL95, MFE 280 respectively) were used to assess the impact of 27HC or the LXR
      agonist GW3965 on proliferation or expression of a luciferase reporter gene under
      the control of LXR- or ER-dependent promoters (LXRE, ERE). Incubation with 27HC
      or GW3965 increased transcription via LXRE in Ishikawa, RL95 and MFE 280 cells (P
      < 0.01). 27HC selectively activated ER-dependent transcription (P < 0.001) in
      Ishikawa cells and promoted proliferation of both Ishikawa and RL95 cells (P <
      0.001). In MFE 280 cells, 27HC did not alter proliferation but selective
      targeting of LXR with GW3965 significantly reduced cell proliferation (P <
      0.0001). These novel results suggest that 27HC can contribute to risk of EC by
      promoting proliferation of endometrial cancer epithelial cells and highlight LXR
      as a potential therapeutic target in the treatment of advanced disease.

PMID- 29371333
TI  - MECHANISMS IN ENDOCRINOLOGY: SGLT2 inhibitors: clinical benefits by restoration
      of normal diurnal metabolism?
AB  - Type 2 diabetes (T2D) is associated with inhibition of autophagic and lysosomal
      housekeeping processes that detrimentally affect key organ functioning; a process
      likely to be exacerbated by conventional insulin-driven anabolic therapies. We
      propose that the cardio-renal benefits demonstrated with sodium-glucose
      cotransporter-2 inhibitor (SGLT2i) treatment in T2D partly may be explained by
      their ability to drive consistent, overnight periods of increased catabolism
      brought about by constant glucosuria. Key steps driving this catabolic mechanism
      include: a raised glucagon/insulin ratio initially depleting glycogen in the
      liver and ultimately activating gluconeogenesis utilizing circulating amino acids
      (AAs); a general fuel switch from glucose to free fatty acids (accompanied by a
      change in mitochondrial morphology from a fission to a sustained fusion state
      driven by a decrease in AA levels); a decrease in circulating AAs and insulin
      driving inhibition of mammalian target of rapamycin complex 1 (mTORC1), which
      enhances autophagy/lysosomal degradation of dysfunctional organelles, eventually
      causing a change in mitochondrial morphology from a fission to a sustained fusion
      state. Resumption of eating in the morning restores anabolic biogenesis of new
      and fully functional organelles and proteins. Restoration of diurnal metabolic
      rhythms and flexibility by SGLT2is may have therapeutic implications beyond those
      already demonstrated for the cardio-renal axis and may therefore affect other non
      diabetes disease states.

PMID- 29371334
TI  - Poor compliance and increased mortality, depression and healthcare costs in
      patients with congenital adrenal hyperplasia.
AB  - OBJECTIVES: To evaluate the risks of depression and all-cause mortality,
      healthcare utilisation costs and treatment adherence in congenital adrenal
      hyperplasia (CAH) in the United Kingdom. DESIGN AND METHODS: A retrospective,
      matched-cohort study using UK primary-care data from the Clinical Practice
      Research Datalink linked to hospital and death certification data. Patients
      diagnosed with CAH and having >=1 corticosteroid prescription were matched 1:10
      to reference subjects. Risk of death and lifetime prevalence of depression were
      compared using Cox regression models. Direct financial costs were estimated for
      healthcare contacts. Treatment adherence was measured by medical possession ratio
      (MPR). RESULTS: 605 patients with CAH were identified; 562 were matched. 270 CAH
      patients (2700 controls) were linkable to death-certificate data, with adjusted
      hazard ratio for all-cause mortality 5.17 (95% CI 2.81-9.50). Mean (s.d.) age at
      death in CAH patients was 54.8 (23.9) vs 72.8 (18.0) years in control patients.
      The prevalence ratio of depression in CAH vs control patients was 1.28 (95% CI
      1.13-1.45). Mean (s.d.) annual healthcare costs were higher in CAH than controls:
      at age 0-6 years, L7038 (L14 846) vs L2879 (L13 972, P < 0.001); 7-17 years,
      L3766 (L7494) vs L1232 (L2451, P < 0.001); 18-40 years, L1539 (L872) vs L1344
      (L1620, P = 0.007) and >=41 years, L4204 (L4863) vs L1651 (L2303, P < 0.001).
      Treatment adherence was lowest in adults, with 141 (36%) of 396 eligible patients
      having an MPR <80%. CONCLUSIONS: This first analysis of CAH in routine UK
      healthcare suggests that patients with CAH have increased mortality, depression
      and healthcare utilisation and low treatment adherence.

PMID- 29371335
TI  - Increasing frequency of combination medical therapy in the treatment of
      acromegaly with the GH receptor antagonist pegvisomant.
AB  - Pegvisomant monotherapy is effective and safe in treatment of acromegaly.
      However, some clinicians combine pegvisomant with somatostatin analogues (SSA) or
      dopamine agonist (DA). In this analysis of ACROSTUDY, a long-term non
      interventional study, the use of combination regimens was evaluated. Based on
      their baseline treatment, 2043 patients were retrospectively categorized as: long
      acting SSA combined with pegvisomant, 'Combo SSA' 768 patients (38%); DA combined
      with pegvisomant, 'Combo DA' 123 (6%); pegvisomant monotherapy, 'Peg mono' 1128
      (55%). Treatment patterns changed over the 10-year period, with recent patients
      more likely to receive any combination (20% in 2003 vs 54% in 2012). Combo SSA
      use varied widely among countries from 22% to 78%. Exposure periods of the three
      treatment modalities were defined from pegvisomant start until the last visit in
      ACROSTUDY; patients could switch treatment categories. At year 4, IGF-I was
      normal in 62% of Combo SSA, 63% of Combo DA and 65% of Peg mono groups.
      Pegvisomant was initiated as daily injections in 94% of patients in the Peg mono
      group, 66% of Combo SSA and 91% of Combo DA patients. During 6169 years of
      treatment exposure, 3424 adverse events (AEs) were reported in 946 (51%)
      patients, of which 617 (18%) were serious and 401 (12%) were considered treatment
      related. The reported incidence of serious AEs and treatment-related non-serious
      AEs were similar among the three treatment modalities. This analysis describes
      real-world clinical care and shows favorable efficacy and safety for Peg mono and
      combinations. Novel findings include an increased use of combination therapy over
      time and variability in treatment modalities between countries.

PMID- 29371336
TI  - HAPT2D: high accuracy of prediction of T2D with a model combining basic and
      advanced data depending on availability.
AB  - OBJECTIVE: Type 2 diabetes arises from the interaction of physiological and
      lifestyle risk factors. Our objective was to develop a model for predicting the
      risk of T2D, which could use various amounts of background information. RESEARCH
      DESIGN AND METHODS: We trained a survival analysis model on 8483 people from
      three large Finnish and Spanish data sets, to predict the time until incident
      T2D. All studies included anthropometric data, fasting laboratory values, an oral
      glucose tolerance test (OGTT) and information on co-morbidities and lifestyle
      habits. The variables were grouped into three sets reflecting different degrees
      of information availability. Scenario 1 included background and anthropometric
      information; Scenario 2 added routine laboratory tests; Scenario 3 also added
      results from an OGTT. Predictive performance of these models was compared with
      FINDRISC and Framingham risk scores. RESULTS: The three models predicted T2D risk
      with an average integrated area under the ROC curve equal to 0.83, 0.87 and 0.90,
      respectively, compared with 0.80 and 0.75 obtained using the FINDRISC and
      Framingham risk scores. The results were validated on two independent cohorts.
      Glucose values and particularly 2-h glucose during OGTT (2h-PG) had highest
      predictive value. Smoking, marital and professional status, waist circumference,
      blood pressure, age and gender were also predictive. CONCLUSIONS: Our models
      provide an estimation of patient's risk over time and outweigh FINDRISC and
      Framingham traditional scores for prediction of T2D risk. Of note, the models
      developed in Scenarios 1 and 2, only exploited variables easily available at
      general patient visits.

PMID- 29371337
TI  - Endocrine and metabolic evaluation of classic Klinefelter syndrome and high-grade
      aneuploidies of sexual chromosomes with male phenotype: are they different
      clinical conditions?
AB  - OBJECTIVE: Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy
      in males. As well as classic KS, less frequent higher-grade aneuploidies (HGAs)
      are also possible. While KS and HGAs both involve testicular dysgenesis with
      hypergonadotropic hypogonadism, they differ in many clinical features. The aim of
      this study was to investigate the endocrinal and metabolic differences between KS
      and HGAs. DESIGN: Cross-sectional, case-control study. METHODS: 88 patients with
      KS, 24 with an HGA and 60 healthy controls. Given the known age-related
      differences all subjects were divided by age into subgroups 1, 2 and 3.
      Pituitary, thyroid, gonadal and adrenal functions were investigated in all
      subjects. Metabolic aspects were only evaluated in subjects in subgroups 2 and 3.
      RESULTS: FT4 and FT3 levels were significantly higher in HGA than in KS patients
      in subgroups 1 and 2; in subgroup 3, FT4 was significantly higher in controls
      than in patients. Thyroglobulin was significantly higher in HGA patients in
      subgroup 1 than in KS patients and controls. Hypergonadotropic hypogonadism was
      confirmed in both KS and HGA patients, but was more precocious in the latter, as
      demonstrated by the earlier increase in gonadotropins and the decrease in
      testosterone, DHEA-S and inhibin B. Prolactin was significantly higher in HGA
      patients, starting from subgroup 2. Total and LDL cholesterol were significantly
      higher in HGA patients than in KS patients and controls, while HDL cholesterol
      was higher in controls than in patients. CONCLUSIONS: KS and HGAs should be
      considered as two distinct conditions.

PMID- 29371338
TI  - Persistent Hematuria in ANCA Vasculitis: Ominous or Innocuous?

PMID- 29371339
TI  - Accountability of Dialysis Facilities in Transplant Referral: CMS Needs to
      Collect National Data on Dialysis Facility Kidney Transplant Referrals.

PMID- 29371342
TI  - Draft Genome Sequence of a Leptospira interrogans Strain Isolated from the Urine
      of an Asymptomatic Dog in Thailand.
AB  - In 2014, Leptospira interrogans strain CUDO8 was isolated from the urine of an
      asymptomatic dog in Thailand. Here we report the draft genome sequence of this
      pathogenic bacterium.

PMID- 29371340
TI  - The Utility of Urinalysis in Determining the Risk of Renal Relapse in ANCA
      Associated Vasculitis.
AB  - BACKGROUND AND OBJECTIVES: The significance of persistent hematuria or
      proteinuria in patients with ANCA-associated vasculitis who are otherwise in
      clinical remission is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      post hoc analysis was conducted using participants enrolled in two randomized,
      placebo-controlled clinical trials who had active GN due to ANCA-associated
      vasculitis, had positive ANCA, and achieved remission by month 6. Dipstick and
      microscopic urinalyses were performed at each visit. Persistent hematuria or
      proteinuria for at least 6 months and the cumulative duration of hematuria were
      examined. Renal relapse was defined as new or worsening red blood cell casts
      and/or worsening kidney function according to the Birmingham Vasculitis Activity
      Score for Granulomatosis with Polyangiitis. RESULTS: There were 149 patients
      included in this study: 42% had persistent hematuria, and 43% had persistent
      proteinuria beyond 6 months. Persistent hematuria was associated with a
      significantly higher risk of relapse, even after adjusting for potential
      confounders (subdistribution hazard ratio, 3.99; 95% confidence interval, 1.20 to
      13.25; P=0.02); persistent proteinuria was not associated with renal relapse
      (subdistribution hazard ratio, 1.44; 95% confidence interval, 0.47 to 4.42;
      P=0.53). Furthermore, greater cumulative duration of hematuria was significantly
      associated with a higher risk of renal relapse (adjusted subdistribution hazard
      ratio, 1.08 per each month; 95% confidence interval, 1.03 to 1.12; P<0.01). The
      median time to renal relapse was 22 months. CONCLUSIONS: In patients with ANCA
      associated vasculitis and kidney involvement who achieve remission after
      induction therapy, the presence of persistent hematuria, but not proteinuria, is
      a significant predictor of future renal relapse.

PMID- 29371343
TI  - Complete Genome Sequence of ZG49, a T7-Like Bacteriophage Lytic to Escherichia
      coli Isolates.
AB  - Here, we describe the complete genome sequence of the Escherichia coli
      bacteriophage ZG49, isolated from a sewage sample. ZG49 is a linear double
      stranded DNA T7-like podophage, with a genome of 40,291 bp, containing 44
      predicted open reading frames.

PMID- 29371341
TI  - Standardized Transplantation Referral Ratio to Assess Performance of Transplant
      Referral among Dialysis Facilities.
AB  - BACKGROUND AND OBJECTIVES: For patients with ESRD, referral from a dialysis
      facility to a transplant center for evaluation is an important step toward kidney
      transplantation. However, a standardized measure for assessing clinical
      performance of dialysis facilities transplant access is lacking. We describe
      methodology for a new dialysis facility measure: the Standardized Transplantation
      Referral Ratio. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Transplant
      referral data from 8308 patients with incident ESRD within 249 dialysis
      facilities in the United States state of Georgia were linked with US Renal Data
      System data from January of 2008 to December of 2011, with follow-up through
      December of 2012. Facility-level expected referrals were computed from a two
      stage Cox proportional hazards model after patient case mix risk adjustment
      including demographics and comorbidities. The Standardized Transplantation
      Referral Ratio (95% confidence interval) was calculated as a ratio of observed to
      expected referrals. Measure validity and reliability were assessed. RESULTS: Over
      2008-2011, facility Standardized Transplantation Referral Ratios in Georgia
      ranged from 0 to 4.87 (mean =1.16, SD=0.76). Most (77%) facilities had observed
      referrals as expected, whereas 11% and 12% had Standardized Transplantation
      Referral Ratios significantly greater than and less than expected, respectively.
      Age, race, sex, and comorbid conditions were significantly associated with the
      likelihood of referral, and they were included in risk adjustment for
      Standardized Transplantation Referral Ratio calculations. The Standardized
      Transplantation Referral Ratios were positively associated with evaluation,
      waitlisting, and transplantation (r=0.46, 0.35, and 0.20, respectively; P<0.01).
      On average, approximately 33% of the variability in Standardized Transplantation
      Referral Ratios was attributed to between-facility variation, and 67% of the
      variability in Standardized Transplantation Referral Ratios was attributed to
      within-facility variation. CONCLUSIONS: The majority of observed variation in
      dialysis facility referral performance was due to characteristics within a
      dialysis facility rather than patient factors included in risk adjustment models.
      Our study shows a method for computing a facility-level standardized measure for
      transplant referral on the basis of a pilot sample of Georgia dialysis facilities
      that could be used to monitor transplant referral performance of dialysis
      facilities.

PMID- 29371344
TI  - Whole-Genome Sequence of Mycoplasma bovis Strain Ningxia-1.
AB  - A genome sequence of the Mycoplasma bovis Ningxia-1 strain was tested by Pacific
      Biosciences (PacBio) single-molecule real-time (SMRT) sequencing technology. The
      strain was isolated from a lesioned calf lung in 2013 in Pengyang, Ningxia,
      China. The single circular chromosome of 1,033,629 bp shows differences between
      complete Mycoplasma bovis genome in insertion-like sequences (ISs), integrative
      conjugative elements (ICEs), lipoproteins (LPs), variable surface lipoproteins
      (VSPs), pathogenicity islands (PAIs), etc.

PMID- 29371345
TI  - Genome Sequence of Pseudomonas plecoglossicida Strain NZBD9.
AB  - Pseudomonas plecoglossicida NZBD9 is the causative agent of white nodules in
      cultured large yellow croaker in Fujian Province, China. We sequenced the genome
      of NZBD9 to gain a better understanding of the etiological agent. The genome
      sequence of the bacterium consists of 5.44 million bp, with a G+C content of
      61.9%.

PMID- 29371346
TI  - Full-Genome Sequence of an Enterovirus 71 Strain Isolated from a Throat Swab from
      a Child with Severe Hand-Foot-and-Mouth Disease in Changzhou, China, in 2017.
AB  - The full-length genome sequence of a human enterovirus 71 (EV71) strain
      (EV71/CZTN01/CHN/2017) was isolated from a throat swab from a child in Changzhou,
      China, in 2017. According to the phylogenetic analyses, the full-genome sequence
      in this study belongs to sub-subgenotype C4a.

PMID- 29371347
TI  - Complete Genome Sequences of the Plant Pathogens Dickeya solani RNS 08.23.3.1.A
      and Dickeya dianthicola RNS04.9.
AB  - Dickeya spp. are bacterial pathogens causing soft-rot and blackleg diseases on a
      wide range of ornamental plants and crops. In this paper, we announce the PacBio
      complete genome sequences of the plant pathogens Dickeya solani RNS 08.23.3.1.A
      (PRI3337) and Dickeya dianthicola RNS04.9.

PMID- 29371348
TI  - Genome Sequence of Verrucomicrobium sp. Strain GAS474, a Novel Bacterium Isolated
      from Soil.
AB  - Verrucomicrobium sp. strain GAS474 was isolated from the mineral soil of a
      temperate deciduous forest in central Massachusetts. Here, we present the
      complete genome sequence of this phylogenetically novel organism, which consists
      of a total of 3,763,444 bp on a single scaffold, with a 65.8% GC content and
      3,273 predicted open reading frames.

PMID- 29371349
TI  - Complete Genome Sequence of a Lily virus X Isolate from Japan.
AB  - The complete genome sequence of Lily virus X (LVX), which infects lilies, was
      determined for the first time from lilies in Japan. As with previous reports, the
      genome of the Japanese LVX isolate lacked an AUG start codon for the triple gene
      block protein 3-like region.

PMID- 29371350
TI  - Genome Sequence of "Candidatus Carsonella ruddii" Strain BT from the Psyllid
      Bactericera trigonica.
AB  - The genome of "Candidatus Carsonella ruddii" strain BT from Bactericera trigonica
      in Israel was sequenced. The full-length genome is 173,904 bp long and has a G+C
      content of 14.6%, with 224 predicted open reading frames (ORFs) and 30 RNAs.

PMID- 29371351
TI  - Complete Genome Sequence of a blaCTX-M-1-Harboring Escherichia coli Isolate
      Recovered from Cattle in Germany.
AB  - We describe here the whole-genome sequence and basic characteristics of
      Escherichia coli isolate 15-AB01393, recovered from German beef within a national
      monitoring program in 2015. This isolate was identified as an extended-spectrum
      beta-lactamase-producing E. coli strain of multilocus sequence type (MLST) ST58
      harboring the antimicrobial resistance genes blaCTX-M-1, mph(A), sul2, dfrA5,
      strA, and strB.

PMID- 29371352
TI  - Nuclear, Chloroplast, and Mitochondrial Genome Sequences of the Prospective
      Microalgal Biofuel Strain Picochlorum soloecismus.
AB  - Picochlorum soloecismus is a halotolerant, fast-growing, and moderate-lipid
      producing microalga that is being evaluated as a renewable feedstock for biofuel
      production. Herein, we report on an improved high-quality draft assembly and
      annotation for the nuclear, chloroplast, and mitochondrial genomes of P.
      soloecismus DOE 101.

PMID- 29371353
TI  - First Insights into the Draft Genome Sequence of the Endophyte Paenibacillus
      amylolyticus Strain GM1FR, Isolated from Festuca rubra L.
AB  - Paenibacillus amylolyticus strain GM1FR is an endophyte isolated from aerial
      plant tissues of Festuca rubra L. Here, we report the draft genome sequence (7.3
      Mb) of GM1FR containing 6,241 protein-coding genes, some of which are potentially
      involved in plant growth promotion and biocontrol.

PMID- 29371354
TI  - Draft Genome Sequence of the Endophyte Bacillus mycoides Strain GM5LP Isolated
      from Lolium perenne.
AB  - Bacillus mycoides GM5LP is a Gram-positive endophytic bacterium isolated from
      aerial plant tissues of Lolium perenne L. The 6.0-Mb draft genome harbors 6,132
      protein-coding sequences, some of which might be involved in the biosynthesis of
      antimicrobial substances.

PMID- 29371355
TI  - Genome Sequence of Rhizobium sullae HCNT1 Isolated from Hedysarum coronarium
      Nodules and Featuring Peculiar Denitrification Phenotypes.
AB  - The genome sequence of Rhizobium sullae strain HCNT1, isolated from root nodules
      of the legume Hedysarum coronarium growing in wild stands in Tuscany, Italy, is
      described here. Unlike other R. sullae strains, this isolate features a truncated
      denitrification pathway lacking NO/N2O reductase activity and displaying high
      sensitivity to nitrite under anaerobic conditions.

PMID- 29371356
TI  - Complete Nucleotide Sequence of a Novel Hibiscus-Infecting Cilevirus from Florida
      and Its Relationship with Closely Associated Cileviruses.
AB  - The complete nucleotide sequence of a recently discovered Florida (FL) isolate of
      hibiscus-infecting cilevirus (HiCV) was determined by Sanger sequencing. The
      movement and coat protein gene sequences of the HiCV-FL isolate are more
      divergent than other genes of the previously sequenced HiCV-HI (Hawaii) isolate.

PMID- 29371357
TI  - Draft Genome Sequence of Telmatospirillum siberiense 26-4b1, an Acidotolerant
      Peatland Alphaproteobacterium Potentially Involved in Sulfur Cycling.
AB  - The facultative anaerobic chemoorganoheterotrophic alphaproteobacterium
      Telmatospirillum siberiense 26-4b1 was isolated from a Siberian peatland. We
      report here a 6.20-Mbp near-complete high-quality draft genome sequence of T.
      siberiense that reveals expected and novel metabolic potential for the genus
      Telmatospirillum, including genes for sulfur oxidation.

PMID- 29371358
TI  - Whole-Genome Sequences of Zika Virus FLR Strains after Passage in Vero or C6/36
      Cells.
AB  - We report 26 complete genomes of Zika virus (ZIKV) isolated after passaging the
      Zika virus strain FLR in mosquito (C6/36) and mammalian (Vero) cell lines. The
      consensus ZIKV genomes we recovered show greater than 99% nucleotide identify
      with each other and with the FLR strain used as input.

PMID- 29371359
TI  - Draft Genome Sequence of Pseudomonas putida CA-3, a Bacterium Capable of Styrene
      Degradation and Medium-Chain-Length Polyhydroxyalkanoate Synthesis.
AB  - Pseudomonas putida strain CA-3 is an industrial bioreactor isolate capable of
      synthesizing biodegradable polyhydroxyalkanoate polymers via the metabolism of
      styrene and other unrelated carbon sources. The pathways involved are subject to
      regulation by global cellular processes. The draft genome sequence is 6,177,154
      bp long and contains 5,608 predicted coding sequences.

PMID- 29371360
TI  - Draft Genome Sequence of the Antimycin-Producing Bacterium Streptomyces sp.
      Strain SM8, Isolated from the Marine Sponge Haliclona simulans.
AB  - Streptomyces sp. strain SM8, isolated from Haliclona simulans, possesses
      antifungal and antibacterial activities and inhibits the calcineurin pathway in
      yeast. The draft genome sequence is 7,145,211 bp, containing 5,929 predicted
      coding sequences. Several secondary metabolite biosynthetic gene clusters are
      present, encoding known and novel metabolites, including antimycin.

PMID- 29371361
TI  - Complete Genome Sequences of Four Toxigenic Clostridium difficile Clinical
      Isolates from Patients of the Lower Hudson Valley, New York, USA.
AB  - Complete genome sequences of four toxigenic Clostridium difficile isolates from
      patients in the lower Hudson Valley, New York, USA, were achieved. These isolates
      represent four common sequence types (ST1, ST2, ST8, and ST42) belonging to two
      distinct phylogenetic clades. All isolates have a 4.0- to 4.2-Mb circular
      chromosome, and one carries a phage.

PMID- 29371362
TI  - Draft Genome Sequence of Tetzosporium hominis VT-49 gen. nov., sp. nov., Isolated
      from the Dental Decay Plaque of a Patient with Periodontitis.
AB  - Here, we report the draft genome sequence of Tetzosporium hominis VT-49 gen.
      nov., sp. nov., isolated from the dental plaque of a patient with severe
      periodontal disease. The draft genome sequence was 2,780,751 bp in length with a
      43.3% G+C content. We detected 3,001 genes, which are predicted to encode
      proteins that regulate both virulence and antibiotic resistance.

PMID- 29371363
TI  - Complete Genome Sequence of Bacillus velezensis CN026 Exhibiting Antagonistic
      Activity against Gram-Negative Foodborne Pathogens.
AB  - We report here the complete genome sequence of Bacillus velezensis strain CN026,
      a member of the B. subtilis group, which is known for its many industrial
      applications. The genome contains 3,995,812 bp and displays six gene clusters
      potentially involved in strain CN026's activity against Gram-negative foodborne
      pathogens.

PMID- 29371364
TI  - Complete Genome Sequences of Two Porcine Deltacoronavirus Strains, CHN-GD16-03
      and CHN-GD16-05, Isolated in Southern China, 2016.
AB  - We report here the amplification and sequence analysis of two complete genomes of
      newly emerged porcine deltacoronavirus (PDCoV) strains, isolated from diarrhea
      samples from piglets in Guangdong Province in southern China. These genomes
      provide further sequence data for evaluating the relationships among PDCoVs from
      different countries.

PMID- 29371365
TI  - Draft Genome Sequence of Pantoea ananatis Strain 1.38, a Bacterium Isolated from
      the Rhizosphere of Oryza sativa var. Puntal That Shows Biotechnological Potential
      as an Inoculant.
AB  - Pantoea ananatis 1.38 is a strain isolated from the rhizosphere of irrigated rice
      in southern Spain. Its genome was estimated at 4,869,281 bp, with 4,644 coding
      sequences (CDSs). The genome encompasses several CDSs related to plant growth
      promotion, such as that for siderophore metabolism, and virulence genes
      characteristic of pathogenic Pantoea spp. are absent.

PMID- 29371366
TI  - Draft Genome Sequences of Four Salmonella enterica subsp. enterica Serovar
      Enteritidis Strains Implicated in Infections of Avian and Human Hosts.
AB  - Salmonella enterica subsp. enterica serovar Enteritidis is a wide-host-range
      pathogen. Occasionally, it is involved in invasive infections, leading to a high
      mortality rate. Here, we present the draft genome sequences of four S Enteritidis
      strains obtained from human and avian hosts that had been involved in bacteremia,
      gastroenteritis, and primary infections.

PMID- 29371367
TI  - Genome Sequence of a Newly Isolated F2 Subcluster Mycobacteriophage from the
      Black Belt Geological Region of Western Alabama.
AB  - The bacteriophage Demsculpinboyz was discovered in a soil sample from the Black
      Belt region of Alabama using Mycobacterium smegmatis mc2155 as its host. The
      genome is 57,437 bp long and contains 116 protein-coding genes. It belongs to the
      F2 subcluster, which has only five other members.

PMID- 29371368
TI  - Complete Genome Sequence of an Escherichia coli O121:H19 Strain from an Outbreak
      in Canada Associated with Flour.
AB  - Here, we present the first complete genome sequence of an Escherichia coli non
      O157 Shiga-toxin producing isolate, 16-9255, from serotype O121:H19. This strain
      is notable as a clinical case recovered from a recent Canadian flour-associated
      outbreak event.

PMID- 29371369
TI  - Complete Genome Sequence of Mycobacterium sp. Strain 3519A.
AB  - Mycobacterium sp. strain 3519A is a nontuberculous mycobacterium isolated from
      sputum from a Cambodian patient with a pulmonary infection. We report here the
      first complete 7.3-Mbp-long genome sequence of Mycobacterium sp. 3519A with
      66.35% GC content, encoding 7,029 protein-coding genes, 50 tRNAs, and 5 rRNA
      genes.

PMID- 29371370
TI  - Draft Genome Sequences of Two Psychrotolerant Strains, Colwellia polaris MCCC
      1C00015T and Colwellia chukchiensis CGMCC 1.9127T.
AB  - Colwellia polaris MCCC 1C00015T and Colwellia chukchiensis CGMCC 1.9127T are
      psychrotolerant bacteria isolated from the Canadian Basin and Chukchi Sea,
      respectively. Here, we report the draft genome sequences of C. polaris MCCC
      1C00015T and C. chukchiensis CGMCC 1.9127T, which will help reveal how they adapt
      to cold environments.

PMID- 29371371
TI  - Genome Sequence of a Rabies Virus Isolated from a Dog in Chiapas, Mexico, 2013.
AB  - Rabies virus (RABV), a member of the genus Lyssavirus, causes encephalitis that
      is almost always fatal following the onset of clinical signs. Here, we report the
      complete codifying sequence of an RABV isolated from a dog in Mexico. Molecular
      data showed that this strain belongs to the Chiapas lineage.

PMID- 29371372
TI  - Erratum for Rajkumari et al., "Draft Genome Sequence of Klebsiella pneumoniae
      AWD5".

PMID- 29371373
TI  - Interventional treatments and risk factors in patients born with hypoplastic left
      heart syndrome in England and Wales from 2000 to 2015.
AB  - OBJECTIVE: To describe the long-term outcomes, treatment pathways and risk
      factors for patients diagnosed with hypoplastic left heart syndrome (HLHS) in
      England and Wales. METHODS: The UK's national audit database captures every
      procedure undertaken for congenital heart disease and updated life status for
      resident patients in England and Wales. Patients with HLHS born between 2000 and
      2015 were identified using codes from the International Paediatric and Congenital
      Cardiac Code. RESULTS: There were 976 patients with HLHS. Of these, 9.6% had a
      prepathway intervention, 89.5% underwent a traditional pathway of staged
      palliation and 6.4% of infants underwent a hybrid pathway. Patients undergoing
      prepathway procedures or the hybrid pathway were more complex, exhibiting higher
      rates of prematurity and acquired comorbidity. Prepathway intervention was
      associated with the highest in-hospital mortality (34.0%).44.6% of patients had
      an off-pathway procedure after their primary procedure, most frequently stenting
      or dilation of residual or recoarctation and most commonly occurring between
      stage 1 and stage 2.The survival rate at 1 year and 5 years was 60.7% (95% CI
      57.5 to 63.7) and 56.3% (95% CI 53.0 to 59.5), respectively. Patients with an
      antenatal diagnosis (multivariable HR (MHR) 1.63 (95% CI 1.12 to 2.38)), low
      weight (<2.5 kg) (MHR 1.49 (95% CI 1.05 to 2.11)) or the presence of an acquired
      comorbidity (MHR 2.04 (95% CI 1.30 to 3.19)) were less likely to survive.
      CONCLUSION: Treatment pathways among patients with HLHS are complex and variable.
      It is essential that the long-term outcomes of conditions like HLHS that require
      serial interventions are studied to provide a fuller picture and to inform
      quality assurance and improvement.

PMID- 29371374
TI  - Reasons for and consequences of oral anticoagulant underuse in atrial
      fibrillation with heart failure.
AB  - OBJECTIVE: Atrial fibrillation (AF) is common in patients with heart failure
      (HF), and oral anticoagulants (OAC) are indicated. The aim was to assess
      prevalence of, predictors of and consequences of OAC non-use. METHODS: We
      included patients with AF, HF and no previous valve replacement from the Swedish
      Heart Failure Registry. High and low CHA2DS2-VASc and HAS-BLED scores were
      defined as above/below median. Multivariable logistic regressions were used to
      assess the associations between baseline characteristics and OAC use and between
      CHA2DS2-VASc and HAS-BLED scores and OAC use. Multivariable Cox regressions were
      used to assess associations between CHA2DS2-VASc and HAS-BLED scores, OAC use and
      two composite outcomes: all-cause death/stroke and all-cause death/major
      bleeding. RESULTS: Of 21 865 patients, only 12 659 (58%) received OAC. Selected
      predictors of OAC non-use were treatment with platelet inhibitors, less use of HF
      treatments, paroxysmal AF, history of bleeding, no previous stroke, planned
      follow-up in primary care, older age, living alone, lower income and variables
      associated with more severe HF. For each 1-unit increase in CHA2DS2-VASc and HAS
      BLED, the ORs (95% CI) of OAC use were 1.24 (1.21-1.27) and 0.32 (0.30-0.33), and
      the HRs for death/stroke were 1.08 (1.06-1.10) and for death/major bleeding 1.18
      (1.15-1.21), respectively. For high versus low CHA2DS2-VASc and HAS-BLED, the ORs
      of OAC use were 1.23 (1.15-1.32) and 0.20 (0.19-0.21), and the HRs for
      death/stroke were 1.25 (1.19-1.30) and for death/major bleeding 1.28 (1.21-1.34),
      respectively. CONCLUSIONS: Patients with AF and concomitant HF do not receive OAC
      on rational grounds. Bleeding risk inappropriately affects decision-making more
      than stroke risk.

PMID- 29371375
TI  - Socioeconomic status and outcomes in heart failure with reduced ejection
      fraction.

PMID- 29371376
TI  - Renin-angiotensin-aldosterone blockade reduces atrial fibrillation in
      hypertrophic cardiomyopathy.
AB  - OBJECTIVES: Atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) is
      associated with increased mortality, mainly mediated by increased thromboembolic
      events and progressive heart failure. Many studies suggested inhibition of renin
      angiotensin-aldosterone system (RAAS) could reduce new AF in various clinical
      conditions. However, evidence concerning the effects of RAAS inhibitors on AF
      prevention remains unclear in HCM. Our study is to investigate whether treatment
      with ACE inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) could lower
      the risk of new AF in HCM. METHODS: We conducted a retrospective study including
      subjects diagnosed HCM between January 1997 and December 2013 by using a
      nationwide database covering almost all Taiwanese from National Health Research
      Institute. All participants, aged 18 or older, had no ACEIs or ARBs exposure or
      AF diagnosis before enrolment. Propensity score matching and multivariate Cox
      hazard regression were employed to estimate the risk of new AF occurrence.
      RESULTS: Total 18 266 subjects were included in the analysis with median follow
      up duration 8.13 years. Patients taking ACEIs or ARBs are associated with lower
      risk of developing new AF than those without taking neither of medications (3.16%
      vs 5.65%, relative risk 0.56 (95% CI 0.49 to 0.64), HR 0.572 (95% CI 0.480 to
      0.683)). The correlation is more prominent with longer ACEIs or ARBs treatment
      (HRs from T1 to T3: 0.741, 0.579, 0.337, P<0.001). These results remain
      consistent after propensity score adjustment. CONCLUSION: In patients with HCM,
      lower risk of new AF is observed in patients treated with either ACEIs or ARBs
      compared with those receiving neither of these medications.

PMID- 29371377
TI  - The association between air pollution and the incidence of idiopathic pulmonary
      fibrosis in Northern Italy.
AB  - Acute exacerbations and worsening of idiopathic pulmonary fibrosis (IPF) have
      been associated with exposure to ozone (O3), nitrogen dioxide (NO2) and
      particulate matter, but chronic exposure to air pollution might also affect the
      incidence of IPF. We investigated the association between chronic exposure to
      NO2, O3 and particulate matter with an aerodynamic diameter <10 MUm (PM10) and
      IPF incidence in Northern Italy between 2005 and 2010.Daily predictions of PM10
      concentrations were obtained from spatiotemporal models, and NO2 and O3 hourly
      concentrations from fixed monitoring stations. We identified areas with
      homogenous exposure to each pollutant. We built negative binomial models to
      assess the association between area-specific IPF incidence rate, estimated
      through administrative databases, and average overall and seasonal PM10, NO2, and
      8-hour maximum O3 concentrations.Using unadjusted models, an increment of 10 ug.m
      3 in NO2 concentration was associated with an increase between 7.93% (95% CI 0.36
      16.08%) and 8.41% (95% CI -0.23-17.80%) in IPF incidence rate, depending on the
      season. After adjustment for potential confounders, estimated effects were
      similar in magnitude, but with larger confidence intervals.Although confirmatory
      studies are needed, our results trace a potential association between exposure to
      traffic pollution and the development of IPF.

PMID- 29371378
TI  - Phenotypes of organ involvement in sarcoidosis.
AB  - Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto
      unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in
      Sarcoidosis) project represents a European multicentre study to investigate the
      influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype
      module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were
      phenotyped at 31 study centres according to a standardised protocol.From this
      module, we found that patients with acute onset were mainly female, young and of
      Scadding type I or II. Female patients showed a significantly higher frequency of
      eye and skin involvement, and complained more of fatigue. Based on
      multidimensional correspondence analysis and subsequent cluster analysis,
      patients could be clearly stratified into five distinct, yet undescribed,
      subgroups according to predominant organ involvement: 1) abdominal organ
      involvement, 2) ocular-cardiac-cutaneous-central nervous system disease
      involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and
      intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These
      five new clinical phenotypes will be useful to recruit homogenous cohorts in
      future biomedical studies.

PMID- 29371380
TI  - The inflammatory cell landscape in the lungs of patients with idiopathic
      pulmonary arterial hypertension.
AB  - Increasing evidence points towards an inflammatory component underlying pulmonary
      hypertension. However, the conclusive characterisation of multiple inflammatory
      cell populations in the lung is challenging due to the complexity of marker
      specificity and tissue inaccessibility. We used an unbiased computational flow
      cytometry approach to delineate the inflammatory landscape of idiopathic
      pulmonary arterial hypertension (IPAH) and healthy donor lungs.Donor and IPAH
      samples were discriminated clearly using principal component analysis to reduce
      the multidimensional data obtained from single-cell flow cytometry analysis. In
      IPAH lungs, the predominant CD45+ cell type switched from neutrophils to CD3+ T
      cells, with increases in CD4+, CD8+ and gammadeltaT-cell subsets. Additionally,
      diversely activated classical myeloid-derived dendritic cells (CD14-HLA
      DR+CD11c+CD1a+/-) and nonclassical plasmacytoid dendritic cells (pDCs; CD14-CD11c
      CD123+HLA-DR+), together with mast cells and basophils, were more abundant in
      IPAH samples. We describe, for the first time, the presence and regulation of two
      cell types in IPAH, gammadeltaT-cells and pDCs, which link innate and adaptive
      immunity.With our high-throughput flow cytometry with multidimensional dataset
      analysis, we have revealed the interactive interplay between multiple
      inflammatory cells is a crucial part of their integrative network. The
      identification of gammadeltaT-cells and pDCs in this disease potentially provides
      a missing link between IPAH, autoimmunity and inflammation.

PMID- 29371379
TI  - Effects of inspiratory muscle training on dyspnoea in severe COPD patients during
      pulmonary rehabilitation: controlled randomised trial.
AB  - The benefit of inspiratory muscle training (IMT) combined with a pulmonary
      rehabilitation programme (PRP) is uncertain. We aimed to demonstrate that, in
      severe and very severe chronic obstructive pulmonary disease (COPD) patients, IMT
      performed during a PRP is associated with an improvement of dyspnoea.In a single
      blind randomised controlled trial, 150 severe or very severe COPD patients were
      allocated to follow PRP+IMT versus PRP alone. The evaluations were performed at
      inclusion and after 4 weeks. The primary outcome was the change in dyspnoea using
      the Multidimensional Dyspnoea Profile questionnaire at the end of a 6-min walk
      test (6MWT) at 4 weeks. Secondary outcomes were changes in dyspnoea using the
      Borg (end of the 6MWT) and modified Medical Research Council scales and in
      functional parameters (maximal inspiratory pressure (PImax), inspiratory
      capacity, 6MWT and quality of life). All analyses were performed on an intention
      to-treat basis.Dyspnoea decreased significantly in both groups; however, the
      improvement of dyspnoea was not statistically different between the two groups.
      We only found a statistically significant greater increase of PImax after IMT+PRP
      than after PRP alone.In this trial including severe or very severe COPD patients,
      we did not find a significant benefit of IMT during PRP+IMT as compared to PRP
      alone on dyspnoea, despite a significantly higher improvement of PImax in the IMT
      group.

PMID- 29371381
TI  - Inhaled diesel exhaust alters the allergen-induced bronchial secretome in humans.
AB  - Diesel exhaust (DE) is a paradigm for traffic-related air pollution. Human
      adaptation to DE is poorly understood and currently based on oversimplified
      models. DE promotes allergic responses, but protein expression changes mediated
      by this interaction have not been systematically investigated. The aim of this
      study was to define the effect of inhaled DE on allergen-induced proteins in the
      lung.We performed a randomised and blinded controlled human crossover exposure
      study. Participants inhaled filtered air or DE; thereafter, contralateral lung
      segments were challenged with allergen or saline. Using label-free quantitative
      proteomics, we comprehensively defined DE-mediated alteration of allergen-driven
      secreted proteins (secretome) in bronchoalveolar lavage. We further examined
      expression of proteins selected from the secretome data in independent validation
      experiments using Western blots, ELISA and immunohistochemistry.We identified
      protein changes unique to co-exposure (DE+allergen), undetected with mono
      exposures (DE or allergen alone). Validation studies confirmed that specific
      proteins (e.g. the antimicrobial peptide cystatin-SA) were significantly enhanced
      with DE+allergen compared to either mono-exposure.This study demonstrates that
      common environmental co-exposures can uniquely alter protein responses in the
      lungs, illuminating biology that mono-exposures cannot. This study highlights the
      value of complex human in vivo models in detailing airway responses to inhaled
      pollution.

PMID- 29371382
TI  - Inspiratory muscle training does not improve clinical outcomes in 3-week COPD
      rehabilitation: results from a randomised controlled trial.
AB  - The value of inspiratory muscle training (IMT) in pulmonary rehabilitation in
      chronic obstructive pulmonary disease (COPD) is unclear. The RIMTCORE (Routine
      Inspiratory Muscle Training within COPD Rehabilitation) randomised controlled
      trial examined the effectiveness of IMT added to pulmonary rehabilitation.In
      total, 611 COPD patients (Global Initiative for Chronic Obstructive Lung Disease
      stage II-IV) received a 3-week inpatient pulmonary rehabilitation, of which 602
      patients were included in the intention-to-treat analyses. The intervention group
      (n=300) received highly intensive IMT and the control group (n=302) received sham
      IMT. The primary outcome was maximal inspiratory pressure (PImax). The secondary
      outcomes were 6-min walk distance, dyspnoea, quality of life and lung function.
      Outcomes were assessed pre- and post-pulmonary rehabilitation. ANCOVA was
      used.The intervention group showed higher effects in PImax (p<0.001) and forced
      inspiratory volume in 1 s (p=0.013). All other outcomes in both study groups
      improved significantly, but without further between-group differences. Sex and
      pulmonary rehabilitation admission shortly after hospitalisation modified quality
      of life effects.IMT as an add-on to a 3-week pulmonary rehabilitation improves
      inspiratory muscle strength, but does not provide additional benefits in terms of
      exercise capacity, quality of life or dyspnoea. A general recommendation for COPD
      patients to add IMT to a 3-week pulmonary rehabilitation cannot be made.

PMID- 29371383
TI  - RESPIRE 1: a phase III placebo-controlled randomised trial of ciprofloxacin dry
      powder for inhalation in non-cystic fibrosis bronchiectasis.
AB  - We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation
      (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more
      exacerbations in the previous year and pre-defined bacteria in sputum.In this
      phase III, double-blind, placebo-controlled trial, patients were randomised 2:1
      to twice-daily ciprofloxacin DPI 32.5 mg or placebo in two treatment regimens
      consisting of on/off treatment cycles of 14 or 28 days for 48 weeks. The primary
      end-points were time to first exacerbation and frequency of exacerbations.A total
      of 416 patients were randomised to the 14-day on/off regimen (ciprofloxacin DPI
      (n=137) and placebo (n=68)) or the 28-day on/off regimen (ciprofloxacin DPI
      (n=141) and placebo (n=70)). Ciprofloxacin DPI 14 days on/off significantly
      prolonged time to first exacerbation versus pooled placebo (median time >336
      versus 186 days; hazard ratio 0.53, 97.5% CI 0.36-0.80; p=0.0005) and reduced the
      frequency of exacerbations compared with matching placebo by 39% (mean number of
      exacerbations 0.6 versus 1.0; incidence rate ratio 0.61, 97.5% CI 0.40-0.91;
      p=0.0061). Outcomes for ciprofloxacin DPI 28 days on/off were not statistically
      significantly different from placebo. The safety profile of ciprofloxacin DPI was
      favourable.Ciprofloxacin DPI was well tolerated and has the potential to be an
      effective treatment option in non-cystic fibrosis bronchiectasis.

PMID- 29371384
TI  - RESPIRE 2: a phase III placebo-controlled randomised trial of ciprofloxacin dry
      powder for inhalation in non-cystic fibrosis bronchiectasis.
AB  - We evaluated the efficacy and safety of ciprofloxacin dry powder for inhalation
      (DPI) in patients with non-cystic fibrosis bronchiectasis, two or more
      exacerbations in the previous year and predefined sputum bacteria.Patients were
      randomised 2:1 to twice-daily ciprofloxacin DPI 32.5 mg or placebo in 14- or 28
      day on/off treatment cycles for 48 weeks. Primary end-points were time to first
      exacerbation and frequency of exacerbations. Enrolling countries and alpha level
      split (0.049 and 0.001 for 14- and 28-day cycles, respectively) differed from
      RESPIRE 1.Patients were randomised to ciprofloxacin DPI (14 days on/off (n=176)
      or 28 days on/off (n=171)) or placebo (14 days on/off (n=88) or 28 days on/off
      (n=86)). The exacerbation rate was low across treatment arms (mean+/-sd 0.6+/
      0.9). Active treatment showed trends to prolonged time to first exacerbation
      (ciprofloxacin DPI 14 days on/off: hazard ratio 0.87, 95.1% CI 0.62-1.21;
      p=0.3965; ciprofloxacin DPI 28 days on/off: hazard ratio 0.71, 99.9% CI 0.39
      1.27; p=0.0511) and reduced frequency of exacerbations (ciprofloxacin DPI 14 days
      on/off: incidence rate ratio 0.83, 95.1% CI 0.59-1.17; p=0.2862; ciprofloxacin
      DPI 28 days on/off: incidence rate ratio 0.55, 99.9% CI 0.30-1.02; p=0.0014),
      although neither achieved statistical significance. Ciprofloxacin DPI was well
      tolerated.Trends towards clinical benefit were seen with ciprofloxacin DPI, but
      primary end-points were not met.

PMID- 29371385
TI  - Both moderate and severe exacerbations accelerate physical activity decline in
      COPD patients.

PMID- 29371386
TI  - Tuberculosis and tobacco: is there any epidemiological association?

PMID- 29371387
TI  - Eosinophils in COPD: how many swallows make a summer?

PMID- 29371388
TI  - Chronic breathlessness: re-thinking the symptom.

PMID- 29371389
TI  - Inspiratory muscle training in stable COPD patients: enough is enough?

PMID- 29371390
TI  - Chronic breathlessness: re-thinking the symptom.

PMID- 29371391
TI  - Chronic breathlessness: re-thinking the symptom.

PMID- 29371392
TI  - How does inflammation contribute to pulmonary hypertension?

PMID- 29371393
TI  - RESPIRE: breathing new life into bronchiectasis.

PMID- 29371394
TI  - Is chronic exposure to air pollutants a risk factor for the development of
      idiopathic pulmonary fibrosis?

PMID- 29371395
TI  - It's time to evolve from Scadding: phenotyping sarcoidosis.

PMID- 29371396
TI  - The cytochrome P450 24A1 interaction with adrenodoxin relies on multiple
      recognition sites that vary among species.
AB  - Mitochondrial cytochromes P450 (P450s) are responsible for important metabolic
      reactions, including steps involved in steroid and vitamin D metabolism. The
      mitochondrial P450 24A1 (CYP24A1) is responsible for deactivation of the
      bioactive form of vitamin D, 1,25(OH)2D3. Its function relies on formation of a
      P450-redox partner complex with the ferredoxin and electron donor adrenodoxin
      (Adx). However, very little is known about how the Adx-CYP24A1 complex forms. In
      this study, we report the results of solution NMR in which we monitor
      isotopically labeled full-length Adx as it binds CYP24A1 in complex with the P450
      inhibitor clotrimazole. The NMR titration data suggested a mode for P450-Adx
      interactions in which formation of the complex relies on contributions from
      multiple recognition sites on the Adx core domain, some of which have not
      previously been reported. To evaluate differences among CYP24A1-Adx complexes
      from different mammalian species and displaying distinct regioselectivity for
      1,25(OH)2D3, all bound spectra were acquired in parallel for human (carbon-23 and
      -24 hydroxylase), rat (carbon-24 hydroxylase), and opossum (carbon-23
      hydroxylase) CYP24A1 isoforms. Binding data from a series of single and double
      charge-neutralizing substitutions of Adx confirmed that species-specific CYP24A1
      isoforms differ in binding to Adx, providing evidence that variations in redox
      partner interactions correlate with P450 regioselectivity. In summary, these
      findings reveal that CYP24A1-Adx interactions rely on several recognition sites
      and that variations in CYP24A1 isoforms modulate formation of the complex, thus
      providing insight into the variable and complex nature of mitochondrial P450-Adx
      interactions.

PMID- 29371397
TI  - Transcriptional and post-transcriptional regulation of autophagy in the yeast
      Saccharomyces cerevisiae.
AB  - Autophagy is a highly conserved catabolic pathway that is vital for development,
      cell survival, and the degradation of dysfunctional organelles and potentially
      toxic aggregates. Dysregulation of autophagy is associated with cancer,
      neurodegeneration, and lysosomal storage diseases. Accordingly, autophagy is
      precisely regulated at multiple levels (transcriptional, post-transcriptional,
      translational, and post-translational) to prevent aberrant activity. Various
      model organisms are used to study autophagy, but the baker's yeast Saccharomyces
      cerevisiae continues to be advantageous for genetic and biochemical analysis of
      non-selective and selective autophagy. In this Minireview, we focus on the
      cellular mechanisms that regulate autophagy transcriptionally and post
      transcriptionally in S. cerevisiae.

PMID- 29371398
TI  - A molecular perspective of mammalian autophagosome biogenesis.
AB  - Autophagy is a highly conserved process and is essential for the maintenance of
      cellular homeostasis. Autophagy occurs at a basal level in all cells, but it can
      be up-regulated during stress, starvation, or infection. Misregulation of
      autophagy has been linked to various disorders, including cancer,
      neurodegeneration, and immune diseases. Here, we discuss the essential proteins
      acting in the formation of an autophagosome, with a focus on the ULK and VPS34
      kinase complexes, phosphatidylinositol 3-phosphate effector proteins, and the
      transmembrane autophagy-related protein ATG9. The function and regulation of
      these and other autophagy-related proteins acting during formation will be
      addressed, in particular during amino acid starvation.

PMID- 29371399
TI  - Modular domain swapping among the bacterial cytotoxic necrotizing factor (CNF)
      family for efficient cargo delivery into mammalian cells.
AB  - Modular AB-type bacterial protein toxins target mammalian host cells with high
      specificity and deliver their toxic cargo into the cytosol. Hence, these toxins
      are being explored as agents for targeted cytosolic delivery in biomedical and
      research applications. The cytotoxic necrotizing factor (CNF) family is unique
      among these toxins in that their homologous sequences are found in a wide array
      of bacteria, and their activity domains are packaged in various delivery systems.
      Here, to study how CNF cargo and delivery modules can be assembled for efficient
      cytosolic delivery, we generated chimeric toxins by swapping functional domains
      among CNF1, CNF2, CNF3, and CNFy. Chimeras with a CNFy delivery vehicle were more
      stably expressed, but were less efficient at cargo delivery into HEK293-T cells.
      We also found that CNFy cargo is the most universally compatible and that CNF3
      delivery vehicle is the most flexible and efficient at delivering cargo. These
      findings suggest that domains within proteins can be swapped and accommodate each
      other for efficient function and that an individual domain could be engineered
      for compatibility with multiple partner domains. We anticipate that our insights
      could help inform chemical biology approaches to develop toxin-based cargo
      delivery platforms for cytosolic cargo delivery of therapeutics or molecular
      probes into mammalian cells.

PMID- 29371402
TI  - Molecular Imaging in Cancer Drug Development.
AB  - Development of new oncology drugs has increased since the improved understanding
      of cancer's complex biology. The oncology field has become the top therapeutic
      research area for new drugs. However, only a limited number of drugs entering
      clinical trials will be approved for use as the standard of care for cancer
      patients. Molecular imaging is increasingly perceived as a tool to support go/no
      go decisions early during drug development. It encompasses a wide range of
      techniques that include radiolabeling a compound of interest followed by
      visualization with SPECT or PET. Radiolabeling can be performed using a variety
      of radionuclides, which are preferably matched to the compound on the basis of
      size and half-life. Imaging can provide information on drug behavior in vivo,
      whole-body drug target visualization, and heterogeneity in drug target
      expression. This review focuses on current applications of molecular imaging in
      the development of small molecules, antibodies, and antihormonal anticancer
      drugs.

PMID- 29371400
TI  - Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel.
AB  - Voltage-gated, sodium ion-selective channels (NaV) generate electrical signals
      contributing to the upstroke of the action potential in animals. NaVs are also
      found in bacteria and are members of a larger family of tetrameric voltage-gated
      channels that includes CaVs, KVs, and NaVs. Prokaryotic NaVs likely emerged from
      a homotetrameric Ca2+-selective voltage-gated progenerator, and later developed
      Na+ selectivity independently. The NaV signaling complex in eukaryotes contains
      auxiliary proteins, termed beta (beta) subunits, which are potent modulators of
      the expression profiles and voltage-gated properties of the NaV pore, but it is
      unknown whether they can functionally interact with prokaryotic NaV channels.
      Herein, we report that the eukaryotic NaVbeta1-subunit isoform interacts with and
      enhances the surface expression as well as the voltage-dependent gating
      properties of the bacterial NaV, NaChBac in Xenopus oocytes. A phylogenetic
      analysis of the beta-subunit gene family proteins confirms that these proteins
      appeared roughly 420 million years ago and that they have no clear homologues in
      bacterial phyla. However, a comparison between eukaryotic and bacterial NaV
      structures highlighted the presence of a conserved fold, which could support
      interactions with the beta-subunit. Our electrophysiological, biochemical,
      structural, and bioinformatics results suggests that the prerequisites for beta
      subunit regulation are an evolutionarily stable and intrinsic property of some
      voltage-gated channels.

PMID- 29371403
TI  - Molecular Imaging of Prostate Cancer: Choosing the Right Agent.

PMID- 29371401
TI  - Uncoupling proteins 1 and 2 (UCP1 and UCP2) from Arabidopsis thaliana are
      mitochondrial transporters of aspartate, glutamate, and dicarboxylates.
AB  - The Arabidopsis thaliana genome contains 58 members of the solute carrier family
      SLC25, also called the mitochondrial carrier family, many of which have been
      shown to transport specific metabolites, nucleotides, and cofactors across the
      mitochondrial membrane. Here, two Arabidopsis members of this family, AtUCP1 and
      AtUCP2, which were previously thought to be uncoupling proteins and hence named
      UCP1/PUMP1 and UCP2/PUMP2, respectively, are assigned with a novel function. They
      were expressed in bacteria, purified, and reconstituted in phospholipid vesicles.
      Their transport properties demonstrate that they transport amino acids
      (aspartate, glutamate, cysteine sulfinate, and cysteate), dicarboxylates (malate,
      oxaloacetate, and 2-oxoglutarate), phosphate, sulfate, and thiosulfate. Transport
      was saturable and inhibited by mercurials and other mitochondrial carrier
      inhibitors to various degrees. AtUCP1 and AtUCP2 catalyzed a fast counterexchange
      transport as well as a low uniport of substrates, with transport rates of AtUCP1
      being much higher than those of AtUCP2 in both cases. The aspartate/glutamate
      heteroexchange mediated by AtUCP1 and AtUCP2 is electroneutral, in contrast to
      that mediated by the mammalian mitochondrial aspartate glutamate carrier.
      Furthermore, both carriers were found to be targeted to mitochondria. Metabolite
      profiling of single and double knockouts shows changes in organic acid and amino
      acid levels. Notably, AtUCP1 and AtUCP2 are the first reported mitochondrial
      carriers in Arabidopsis to transport aspartate and glutamate. It is proposed that
      the primary function of AtUCP1 and AtUCP2 is to catalyze an
      aspartateout/glutamatein exchange across the mitochondrial membrane and thereby
      contribute to the export of reducing equivalents from the mitochondria in
      photorespiration.

PMID- 29371404
TI  - Concurrent Respiratory Motion Correction of Abdominal PET and Dynamic Contrast
      Enhanced-MRI Using a Compressed Sensing Approach.
AB  - We present an approach for concurrent reconstruction of respiratory motion
      compensated abdominal dynamic contrast-enhanced (DCE)-MRI and PET data in an
      integrated PET/MR scanner. The MR and PET reconstructions share the same motion
      vector fields derived from radial MR data; the approach is robust to changes in
      respiratory pattern and does not increase the total acquisition time. Methods:
      PET and DCE-MRI data of 12 oncologic patients were simultaneously acquired for 6
      min on an integrated PET/MR system after administration of 18F-FDG and gadoterate
      meglumine. Golden-angle radial MR data were continuously acquired simultaneously
      with PET data and sorted into multiple motion phases on the basis of a
      respiratory signal derived directly from the radial MR data. The resulting
      multidimensional dataset was reconstructed using a compressed sensing approach
      that exploits sparsity among respiratory phases. Motion vector fields obtained
      using the full 6-min (MC6-min) and only the last 1 min (MC1-min) of data were
      incorporated into the PET reconstruction to obtain motion-corrected PET images
      and in an MR iterative reconstruction algorithm to produce a series of motion
      corrected DCE-MR images (moco_GRASP). The motion-correction methods (MC6-min and
      MC1-min) were evaluated by qualitative analysis of the MR images and quantitative
      analysis of SUVmax and SUVmean, contrast, signal-to-noise ratio (SNR), and lesion
      volume in the PET images. Results: Motion-corrected MC6-min PET images
      demonstrated 30%, 23%, 34%, and 18% increases in average SUVmax, SUVmean,
      contrast, and SNR and an average 40% reduction in lesion volume with respect to
      the non-motion-corrected PET images. The changes in these figures of merit were
      smaller but still substantial for the MC1-min protocol: 19%, 10%, 15%, and 9%
      increases in average SUVmax, SUVmean, contrast, and SNR; and a 28% reduction in
      lesion volume. Moco_GRASP images were deemed of acceptable or better diagnostic
      image quality with respect to conventional breath-hold Cartesian volumetric
      interpolated breath-hold examination acquisitions. Conclusion: We presented a
      method that allows the simultaneous acquisition of respiratory motion-corrected
      diagnostic quality DCE-MRI and quantitatively accurate PET data in an integrated
      PET/MR scanner with negligible prolongation in acquisition time compared with
      routine PET/DCE-MRI protocols.

PMID- 29371406
TI  - A Prospective Study of Quantitative SPECT/CT for Evaluation of Lung Shunt
      Fraction Before SIRT of Liver Tumors.
AB  - The lung shunt fraction (LSF) is estimated using 99mTc-macroaggregated albumin
      (99mTc-MAA) imaging before selective internal radiotherapy (SIRT) of the liver to
      reduce the risk of pulmonary irradiation. Generally, planar scans are acquired
      after injection of 99mTc-MAA into the hepatic artery. However, the validity of
      this approach is limited by differences in attenuation between liver and lung
      tissue as well as inaccurate segmentation of the organs. The aim of this study
      was to evaluate quantitative SPECT/CT for LSF assessment in a prospective
      clinical cohort. Methods: Fifty consecutive patients intended to undergo SIRT
      were imaged within 1 h after injection of 99mTc-MAA using a SPECT/CT gamma
      camera. Planar scans of the lung and liver region were acquired in anterior and
      posterior views, followed by SPECT/CT scans of the thorax and abdomen. Emission
      data were corrected for scatter, attenuation, and resolution recovery using
      dedicated software. To quantify the radioactivity concentration in the lung,
      liver, urinary bladder and remainder of the thoracoabdominal body, volumes of
      interest were defined on the SPECT/CT images. 99mTc-MAA concentrations were
      calculated as percentage injected dose (%ID). Results: Mean 99mTc-MAA uptake in
      liver and lung accounted for only 79 %ID, whereas 13.1 %ID was present in the
      remainder of the body. In all patients, LSF as calculated from planar scans
      accounted for a median of 6.8% (range, 3.4%-32.3%), whereas the SPECT/CT
      quantitation revealed significantly lower LSF estimates, at a median of 1.9%
      (range, 0.8%-15.7%) (P < 0.0001, Wilcoxon test). On the basis of planar imaging,
      dose reduction or even contraindications to SIRT had to be considered in 10 of 50
      patients, as their LSF was calculated at 10% or more. In contrast, SPECT/CT
      quantitation showed substantial shunting in only 2 of the 50 patients.
      Conclusion: Quantitative SPECT/CT reveals that the LSF is considerably lower than
      shown on planar imaging. Thus, the resulting dose to the lung parenchyma may be
      less than conventionally assumed. However, the safety of the SPECT/CT-derived
      dose range will have to be evaluated.

PMID- 29371405
TI  - Evaluation of PET Brain Radioligands for Imaging Pancreatic beta-Cell Mass:
      Potential Utility of 11C-(+)-PHNO.
AB  - Type 1 diabetes mellitus (T1DM) is characterized by a loss of beta-cells in the
      islets of Langerhans of the pancreas and subsequent deficient insulin secretion
      in response to hyperglycemia. Development of an in vivo test to measure beta-cell
      mass (BCM) would greatly enhance the ability to track diabetes therapies. beta
      cells and neurologic tissues have common cellular receptors and transporters,
      therefore, we screened brain radioligands for their ability to identify beta
      cells. Methods: We examined a beta-cell gene atlas for endocrine pancreas
      receptor targets and cross-referenced these targets with brain radioligands that
      were available at our institution. Twelve healthy control subjects and 2 T1DM
      subjects underwent dynamic PET/CT scans with 6 tracers. Results: The D2/D3
      receptor agonist radioligand 11C-(+)-4-propyl-9-hydroxynaphthoxazine (PHNO) was
      the only radioligand to demonstrate sustained uptake in the pancreas with high
      contrast versus abdominal organs such as the kidneys, liver, and spleen, based on
      the first 30 min of data. Mean SUV from 20 to 30 min demonstrated high uptake of
      11C-(+)-PHNO in healthy controls (SUV, 13.8) with a 71% reduction in a T1DM
      subject with undetectable levels of C-peptide (SUV, 4.0) and a 20% reduction in a
      T1DM subject with fasting C-peptide level of 0.38 ng/mL (SUV, 11.0). SUV in
      abdominal organs outside the pancreas did not show measurable differences between
      the control and T1DM subjects, suggesting that the changes in SUV of 11C-(+)-PHNO
      may be specific to changes in the pancreas between healthy controls and T1DM
      subjects. When D3 and D2 antagonists were used in nonhuman primates, specific
      pancreatic binding (SUVR-1) of 11C-PHNO was reduced by 57% and 38%, respectively.
      Conclusion:11C-(+)-PHNO is a potential marker of BCM, with 2:1 binding of D3
      receptors over D2 receptors. Further in vitro and in vivo studies to establish
      D2/D3 receptor specificity to beta-cells is warranted to characterize 11C-(+)
      PHNO as a candidate for clinical measurement of BCM in healthy control and
      diabetic subjects.

PMID- 29371407
TI  - 68Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important
      Pitfall in Prostate Cancer PET Imaging.
AB  - The study aims to investigate the presence of physiologic prostate-specific
      membrane antigen (68Ga-PSMA)-ligand uptake on PET in cervical, celiac, and sacral
      ganglia of the sympathetic trunk as a pitfall for lymph node metastases in
      prostate cancer imaging. Methods: Four hundred seven patients who underwent Glu
      NH-CO-NH-Lys radiolabeled with 68Ga-gallium N,N-bis[2-hydroxy-5
      (carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid (68Ga-PSMA-HBED-CC) PET
      (combined with a diagnostic CT) were retrospectively analyzed. The number of 68Ga
      PSMA PET-positive cervical, celiac, and sacral ganglia was determined, and the
      configuration and SUVmax of each ganglion were measured. In addition, the
      configuration and SUVmax of adjacent lymph node metastases in the respective
      region (cervical, celiac, or sacral) were determined. Results:68Ga-PSMA-ligand
      uptake above background was detected in 401 (98.5%) patients in any peripheral
      ganglia, in 369 (92%) patients in cervical ganglia, in 363 (89%) patients in
      celiac ganglia, and in 183 (46%) patients in sacral ganglia. The 68Ga-PSMA-ligand
      uptake was highest in celiac (mean SUVmax, 2.9 +/- 0.8 vs. cervical mean SUVmax,
      2.4 +/- 0.6) and sacral (mean SUVmax 1.7 +/- 0.5; both P < 0.0001) ganglia.
      Intraindividually there was a statistically significant but weak to moderate
      correlation between the 68Ga-PSMA-ligand uptake in cervical versus celiac ganglia
      (R = 0.34, P < 0.0001), cervical versus sacral (R = 0.52, P < 0.0001), and celiac
      versus sacral (R = 0.16, P < 0.05). The 68Ga-PSMA-ligand uptake was significantly
      more intense in adjacent lymph node metastases than the respective ganglia
      (cervical: 18.0 +/- 16.2 vs. 2.4 +/- 0.6, P < 0.0001; celiac: 13.5 +/- 12.3 vs.
      2.9 +/- 0.8, P < 0.0001; sacral: 13.4 +/- 11.6 vs. 1.7 +/- 0.5, P < 0.0001).
      Furthermore, ganglia predominantly exhibit a band-shaped configuration (71.2%),
      followed by a teardrop (26.8%) and only rarely a nodular configuration (2.0%).
      Conversely, lymph node metastases are only rarely band-shaped (1.1%), but more
      often show teardrop (40.3%) or nodular appearance (58.6%) (P < 0.00001).
      Conclusion:68Ga-PSMA-ligand uptake in ganglia along the sympathetic trunk as
      assessed by 68Ga-PSMA-HBED-CC PET represents an important pitfall in prostate
      cancer PET imaging. The 68Ga-PSMA-ligand uptake is higher in celiac ganglia than
      cervical or sacral ganglia, and the level of 68Ga-PSMA-ligand uptake seems to be
      patient-related. For the differentiation between lymph node metastases and
      sympathetic ganglia, both intensity of 68Ga-PSMA-ligand uptake and exact
      localization and configuration of the respective lesion should be examined
      carefully.

PMID- 29371408
TI  - Patient-Specific Computational Model and Dosimetry Calculations for PET/CT of a
      Patient Pregnant with Twins.
AB  - The radiation dose delivered to pregnant patients during radiologic imaging
      procedures raises health concerns because the developing embryo and fetus are
      considered to be highly radiosensitive. To appropriately weigh the diagnostic
      benefits against the radiation risks, the radiologist needs reasonably accurate
      and detailed estimates of the fetal dose. Expanding our previously developed
      series of computational phantoms for pregnant women, we here describe a
      personalized model for twin pregnancy, based on an actual clinical scan. Methods:
      The model is based on a standardized hybrid pregnant female and fetus phantom and
      on a clinical case of a patient who underwent an 18F-FDG PET/CT scan while
      expecting twins at 25 weeks' gestation. This model enabled us to produce a
      realistic physical representation of the pregnant patient and to estimate the
      maternal and fetal organ doses from the 18F-FDG and CT components. The Monte
      Carlo N-Particle Extended general-purpose code was used for radiation transport
      simulation. Results: The 18F-FDG doses for the 2 fetuses were 3.78 and 3.99 mGy,
      and the CT doses were 0.76 and 0.70 mGy, respectively. Therefore, the relative
      contribution of 18F-FDG and CT to the total dose to the fetuses was about 84% and
      16%, respectively. Meanwhile, for 18F-FDG, the calculated personalized absorbed
      dose was about 40%-50% higher than the doses reported by other dosimetry computer
      software tools. Conclusion: Our approach to constructing personalized
      computational models allows estimation of a patient-specific radiation dose, even
      in cases with unusual anatomic features such as a twin pregnancy. Our results
      also show that, even in twins, the fetal organ doses from both 18F-FDG and CT
      present a certain variability linked to the anatomic characteristics. The CT
      fetal dose is smaller than the 18F-FDG PET dose.

PMID- 29371409
TI  - The National Oncology PET Registry (NOPR): A monumental effort by a few leaders.

PMID- 29371410
TI  - Intraindividual Comparison of 99mTc-Methylene Diphosphonate and Prostate-Specific
      Membrane Antigen Ligand 99mTc-MIP-1427 in Patients with Osseous Metastasized
      Prostate Cancer.
AB  - The objective of this study was to evaluate the rate of detection of bone
      metastases obtained with the prostate-specific membrane antigen (PSMA)-targeting
      tracer 99mTc-MIP-1427, as opposed to conventional bone scanning with 99mTc
      methylene diphosphonate (99mTc-MDP), in a collective of patients with known
      advanced-stage osseous metastasized prostate cancer. Methods: Twenty-one patients
      with known metastatic disease were staged with both conventional bone scanning
      and PSMA ligand scintigraphy within a time frame of less than 10 d. Imaging
      included planar whole-body scanning and SPECT or SPECT/CT with 2 bed positions 3
      h after injection of either 500-750 MBq of 99mTc-MIP-1427 or 600-750 MBq of 99mTc
      MDP. Lesions were scored as typical tumor, equivocal (benign/malignant), or
      normal within a standard reporting schema divided into defined anatomic regions.
      Masked and consensus readings were performed with sequential unmasking: planar
      scans first, then SPECT/CT, the best evaluable comparator (including MRI),
      PET/CT, and follow-up examinations. Results: Eleven patients had PSMA-positive
      visceral metastases that were predictably not diagnosed with conventional bone
      scanning. However, SPECT/CT was required to distinguish between soft-tissue
      uptake and overlapping bone. Four patients had extensive 99mTc-MDP-negative bone
      marrow lesions. Seven patients had superscan characteristics on bone scans; in
      contrast, the extent of red marrow involvement was more evident on PSMA scans.
      Only 3 patients had equivalent results on bone scans and PSMA scans. In 16
      patients, more suspect lesions were detected with PSMA scanning than with bone
      scanning. In 2 patients (10%), a PSMA-negative tumor phenotype was present.
      Conclusion: PSMA scanning provided a clear advantage over bone scanning by
      reducing the number of equivocal findings in most patients. SPECT/CT was pivotal
      for differentiating bone metastases from extraosseous tumor lesions.

PMID- 29371411
TI  - Central and peripheral effects of physical exercise without weight reduction in
      obese and lean mice.
AB  - To investigate the central (hypothalamic) and peripheral effects of exercise
      without body weight change in diet-induced obesity (DIO). Twelve-week-old male
      C57Bl/6 mice received a control (C) or a high-fat diet (H). Half of them had free
      access to running wheels for 5 days/week for 10 weeks (CE) and HE, respectively).
      Hypothalamic expression of genes related to energy homeostasis, and leptin (Stat3
      and p-Stat3) and insulin (Akt and p-Akt) signaling were evaluated. Glucose and
      leptin tolerance, peripheral insulin sensitivity, and plasma insulin, leptin and
      adiponectin were determined. Perigonadal and retroperitoneal fat depots were
      increased by diet but reduced by exercise despite lack of effect of exercise on
      body weight. Blood glucose during intraperitoneal glucose tolerance test (ipGTT)
      was higher and glucose decay during intraperitoneal insulin tolerance test
      (ipITT) was lower in H and HE compared with C and CE. Exercise increased liver p
      Akt expression and reduced fast glycemia. High-fat diet increased plasma insulin
      and leptin. Exercise had no effect on insulin but decreased leptin and increased
      adiponectin. Leptin inhibited food intake in all groups. Hypothalamic total and p
      Stat3 and Akt were similar amongst the groups despite higher plasma levels of
      leptin and insulin in H and HE mice. High-fat diet modulated gene expression
      favoring a positive energy balance. Exercise only marginally changed the gene
      expression. Exercise induced positive changes (decreased fast glycemia and fat
      depots; increased liver insulin signaling and adiponectin concentration) without
      weight loss. Thus, despite reducing body weight could bring additional benefits,
      the effects of exercise must not be overlooked when weight reduction is not
      achieved.

PMID- 29371412
TI  - Loss of ABCB4 attenuates the caspase-dependent apoptosis regulating resistance to
      5-Fu in colorectal cancer.
AB  - The adenosine triphosphate-binding cassette (ABC) is a large group of proteins
      involved in material transportation, cellular homeostasis, and closely associated
      with chemoresistance. ATP-binding cassette protein B4 (ABCB4) is a member of ABCs
      which has a similar structure to ABCB1, but fewer researches were performed. The
      present study is aimed to investigate the putative mechanism of ABCB4 in 5
      fluorouracil (5-Fu) resistance. Then, we found that ABCB4 was significantly down
      regulated in the 5-Fu resistant HCT8 cell lines by polymerase chain reaction
      (PCR) and Western blot. The knockdown of ABCB4 by small interfering RNA decreased
      the apoptosis by 5-Fu in resistant HCT8R cell lines without influencing the
      proliferation. Also, we found a lower expression of cleaved caspase and PARP by
      Western blot after the knockdown of ABCB4. However, the knockdown of ABCB4 did
      not influence the proliferation and apoptosis. Furthermore, the histological
      detection of ABCB4 mRNA level in human colorectal cancer tissues and even in the
      recurrent tissues after 5-Fu single-agent chemotherapy was employed to provide
      more concrete evidence that ABCB4 may be a tumor suppressor gene to regulate
      chemoresistance in colorectal cancer. Moreover, a 109-patient cohort revealed
      that ABCB4 predicted a poor recurrence-free survival and overall survival. In
      summary, ABCB4 was down-regulated in the 5-Fu resistant cells and knockdown of
      ABCB4 alleviated the cell apoptosis and predicts a shorter recurrence-free
      survival and overall survival.

PMID- 29371413
TI  - Advancing the science of patient decision aids through reporting guidelines.

PMID- 29371414
TI  - Low body mass index can be associated with the risk and poor outcomes of
      neuromyelitis optica with aquaporin-4 immunoglobulin G in women.

PMID- 29371416
TI  - Bardoxolone-the Phoenix?

PMID- 29371415
TI  - Charting the road forward in psychiatric neurosurgery: proceedings of the 2016
      American Society for Stereotactic and Functional Neurosurgery workshop on
      neuromodulation for psychiatric disorders.
AB  - OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and
      mortality worldwide, and there is a great need for new treatments. In the last
      decade, investigators piloted novel deep brain stimulation (DBS)-based therapies
      for depression and obsessive-compulsive disorder (OCD). Results from recent
      pivotal trials of these therapies, however, did not demonstrate the degree of
      efficacy expected from previous smaller trials. To discuss next steps,
      neurosurgeons, neurologists, psychiatrists and representatives from industry
      convened a workshop sponsored by the American Society for Stereotactic and
      Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we
      summarise the proceedings of the workshop. Participants discussed a number of
      issues of importance to the community. First, we discussed how to interpret
      results from the recent pivotal trials of DBS for OCD and depression. We then
      reviewed what can be learnt from lesions and closed-loop neurostimulation.
      Subsequently, representatives from the National Institutes of Health, the Food
      and Drug Administration and industry discussed their views on neuromodulation for
      psychiatric disorders. In particular, these third parties discussed their
      criteria for moving forward with new trials. Finally, we discussed the best way
      of confirming safety and efficacy of these therapies, including registries and
      clinical trial design. We close by discussing next steps in the journey to new
      neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest
      and motivation remain strong for deep brain stimulation for psychiatric disease.
      Progress will require coordinated efforts by all stakeholders.

PMID- 29371418
TI  - The Benefits of Tubular Proteinuria: An Evolutionary Perspective.

PMID- 29371417
TI  - Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic
      Preconditioning Protection.
AB  - Ischemic preconditioning confers organ-wide protection against subsequent
      ischemic stress. A substantial body of evidence underscores the importance of
      mitochondria adaptation as a critical component of cell protection from ischemia.
      To identify changes in mitochondria protein expression in response to ischemic
      preconditioning, we isolated mitochondria from ischemic preconditioned kidneys
      and sham-treated kidneys as a basis for comparison. The proteomic screen
      identified highly upregulated proteins, including NADP+-dependent isocitrate
      dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer
      cellular protection from injury in murine S3 proximal tubule cells subjected to
      hypoxia. To further evaluate the role of IDH2 in cell protection, we performed
      detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility
      to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated
      the injury-induced rise in serum creatinine (P<0.05) observed in controls and
      increased the mitochondria membrane potential (P<0.05), maximal respiratory
      capacity (P<0.05), and intracellular ATP levels (P<0.05) above those in controls.
      This communication shows that gene delivery of Idh2 can confer organ-wide
      protection against subsequent ischemia-reperfusion injury and mimics ischemic
      preconditioning.

PMID- 29371419
TI  - Plasma Potassium Determines NCC Abundance in Adult Kidney-Specific gammaENaC
      Knockout.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) and the thiazide
      sensitive sodium chloride cotransporter (NCC) are key regulators of sodium and
      potassium and colocalize in the late distal convoluted tubule of the kidney. Loss
      of the alphaENaC subunit leads to a perinatal lethal phenotype characterized by
      sodium loss and hyperkalemia resembling the human syndrome
      pseudohypoaldosteronism type 1 (PHA-I). In adulthood, inducible nephron-specific
      deletion of alphaENaC in mice mimics the lethal phenotype observed in neonates,
      and as in humans, this phenotype is prevented by a high sodium (HNa+)/low
      potassium (LK+) rescue diet. Rescue reflects activation of NCC, which is
      suppressed at baseline by elevated plasma potassium concentration. In this study,
      we investigated the role of the gammaENaC subunit in the PHA-I phenotype. Nephron
      specific gammaENaC knockout mice also presented with salt-wasting syndrome and
      severe hyperkalemia. Unlike mice lacking alphaENaC or betaEpsilonNuaC, an
      HNa+/LK+ diet did not normalize plasma potassium (K+) concentration or increase
      NCC activation. However, when K+ was eliminated from the diet at the time that
      gammaENaC was deleted, plasma K+ concentration and NCC activity remained normal,
      and progressive weight loss was prevented. Loss of the late distal convoluted
      tubule, as well as overall reduced betaENaC subunit expression, may be
      responsible for the more severe hyperkalemia. We conclude that plasma K+
      concentration becomes the determining and limiting factor in regulating NCC
      activity, regardless of Na+ balance in gammaENaC-deficient mice.

PMID- 29371420
TI  - Should We Increase GFR with Bardoxolone in Alport Syndrome?

PMID- 29371421
TI  - Banff Classification of Polyomavirus Nephropathy: A New Tool for Research and
      Clinical Practice.

PMID- 29371422
TI  - Editorial Note: From Both Sides Now.

PMID- 29371423
TI  - Any Progress in the Treatment of Antibody-Mediated Rejection?

PMID- 29371424
TI  - Systematic discovery of antiphage defense systems in the microbial pangenome.
AB  - The arms race between bacteria and phages led to the development of sophisticated
      antiphage defense systems, including CRISPR-Cas and restriction-modification
      systems. Evidence suggests that known and unknown defense systems are located in
      "defense islands" in microbial genomes. Here, we comprehensively characterized
      the bacterial defensive arsenal by examining gene families that are clustered
      next to known defense genes in prokaryotic genomes. Candidate defense systems
      were systematically engineered and validated in model bacteria for their
      antiphage activities. We report nine previously unknown antiphage systems and one
      antiplasmid system that are widespread in microbes and strongly protect against
      foreign invaders. These include systems that adopted components of the bacterial
      flagella and condensin complexes. Our data also suggest a common, ancient
      ancestry of innate immunity components shared between animals, plants, and
      bacteria.

PMID- 29371425
TI  - Defining the earliest step of cardiovascular lineage segregation by single-cell
      RNA-seq.
AB  - Mouse heart development arises from Mesp1-expressing cardiovascular progenitors
      (CPs) that are specified during gastrulation. The molecular processes that
      control early regional and lineage segregation of CPs have been unclear. We
      performed single-cell RNA sequencing of wild-type and Mesp1-null CPs in mice. We
      showed that populations of Mesp1 CPs are molecularly distinct and span the
      continuum between epiblast and later mesodermal cells, including hematopoietic
      progenitors. Single-cell transcriptome analysis of Mesp1-deficient CPs showed
      that Mesp1 is required for the exit from the pluripotent state and the induction
      of the cardiovascular gene expression program. We identified distinct populations
      of Mesp1 CPs that correspond to progenitors committed to different cell lineages
      and regions of the heart, identifying the molecular features associated with
      early lineage restriction and regional segregation of the heart at the early
      stage of mouse gastrulation.

PMID- 29371426
TI  - Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory
      elements.
AB  - To achieve guide RNA (gRNA) multiplexing and an efficient delivery of tens of
      distinct gRNAs into single cells, we developed a molecular assembly strategy
      termed chimeric array of gRNA oligonucleotides (CARGO). We coupled CARGO with
      dCas9 (catalytically dead Cas9) imaging to quantitatively measure the movement of
      enhancers and promoters that undergo differentiation-associated activity changes
      in live embryonic stem cells. Whereas all examined functional elements exhibited
      subdiffusive behavior, their relative mobility increased concurrently with
      transcriptional activation. Furthermore, acute perturbation of RNA polymerase II
      activity can reverse these activity-linked increases in loci mobility. Through
      quantitative CARGO-dCas9 imaging, we provide direct measurements of cis
      regulatory element dynamics in living cells and distinct cellular and activity
      states and uncover an intrinsic connection between cis-regulatory element
      mobility and transcription.

PMID- 29371427
TI  - Strong spin-photon coupling in silicon.
AB  - Long coherence times of single spins in silicon quantum dots make these systems
      highly attractive for quantum computation, but how to scale up spin qubit systems
      remains an open question. As a first step to address this issue, we demonstrate
      the strong coupling of a single electron spin and a single microwave photon. The
      electron spin is trapped in a silicon double quantum dot, and the microwave
      photon is stored in an on-chip high-impedance superconducting resonator. The
      electric field component of the cavity photon couples directly to the charge
      dipole of the electron in the double dot, and indirectly to the electron spin,
      through a strong local magnetic field gradient from a nearby micromagnet. Our
      results provide a route to realizing large networks of quantum dot-based spin
      qubit registers.

PMID- 29371428
TI  - An evolutionarily conserved gene family encodes proton-selective ion channels.
AB  - Ion channels form the basis for cellular electrical signaling. Despite the scores
      of genetically identified ion channels selective for other monatomic ions, only
      one type of proton-selective ion channel has been found in eukaryotic cells. By
      comparative transcriptome analysis of mouse taste receptor cells, we identified
      Otopetrin1 (OTOP1), a protein required for development of gravity-sensing
      otoconia in the vestibular system, as forming a proton-selective ion channel. We
      found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is
      required for their zinc-sensitive proton conductance. Two related murine genes,
      Otop2 and Otop3, and a Drosophila ortholog also encode proton channels.
      Evolutionary conservation of the gene family and its widespread tissue
      distribution suggest a broad role for proton channels in physiology and
      pathophysiology.

PMID- 29371429
TI  - Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing
      conformation.
AB  - The multidrug transporter permeability (P)-glycoprotein is an adenosine
      triphosphate (ATP)-binding cassette exporter responsible for clinical resistance
      to chemotherapy. P-glycoprotein extrudes toxic molecules and drugs from cells
      through ATP-powered conformational changes. Despite decades of effort, only the
      structures of the inward-facing conformation of P-glycoprotein are available.
      Here we present the structure of human P-glycoprotein in the outward-facing
      conformation, determined by cryo-electron microscopy at 3.4-angstrom resolution.
      The two nucleotide-binding domains form a closed dimer occluding two ATP
      molecules. The drug-binding cavity observed in the inward-facing structures is
      reorientated toward the extracellular space and compressed to preclude substrate
      binding. This observation indicates that ATP binding, not hydrolysis, promotes
      substrate release. The structure evokes a model in which the dynamic nature of P
      glycoprotein enables translocation of a large variety of substrates.

PMID- 29371430
TI  - Stroke Prevention in the Very Elderly.

PMID- 29371431
TI  - Patients With Undetermined Stroke Have Increased Atrial Fibrosis: A Cardiac
      Magnetic Resonance Imaging Study.
AB  - BACKGROUND AND PURPOSE: Some patients with ischemic strokes that are currently
      classified as having an undetermined cause may have structural or functional
      changes of the left atrium (LA) and left atrial appendage, which increase their
      risk of thromboembolism. We compared the LA and left atrial appendage of patients
      with different ischemic stroke causes using cardiac magnetic resonance imaging.
      METHODS: We prospectively included a consecutive sample of ischemic stroke
      patients. Patients with structural changes on echocardiography currently
      considered as causal for stroke in the Trial of ORG 10172 in Acute Stroke
      Treatment (TOAST) classification were excluded. A 3-T cardiac magnetic resonance
      imaging was performed. RESULTS: One hundred and eleven patients were evaluated.
      Patients with an undetermined cause had a higher percentage of LA fibrosis
      (P=0.03) than patients with other stroke causes and lower, although not
      statistically significant, values of LA ejection fraction. Patients with atrial
      fibrillation and undetermined stroke cause showed a similar value of atrial
      fibrosis. CONCLUSIONS: The LA phenotype that was found in patients with
      undetermined cause supports the hypothesis that an atrial disease may be
      associated with stroke.

PMID- 29371432
TI  - Size of Ruptured Intracranial Aneurysms Is Decreasing: Twenty-Year Long
      Consecutive Series of Hospitalized Patients.
AB  - BACKGROUND AND PURPOSE: Decrease in the incidence of subarachnoid hemorrhage over
      the past decades has been related to decreased smoking rates, especially among
      <50-year-old people. We studied whether these epidemiological changes are
      reflected in changes in the size and location of ruptured intracranial aneurysms
      (RIAs). METHODS: We identified consecutive patients admitted to a nonprofit
      academic hospital with saccular RIAs between 1989 and 2008. We averaged and
      analyzed mean sizes of RIAs in 4-year admission groups. In statistical analysis,
      we used the chi2 test for categorical variables and the Kruskal-Wallis test to
      assess differences between continuous and categorical variables. For linear trend
      assessments, we used the linear-by-linear association and ANOVA tests. RESULTS:
      Of 2660 consecutive patients (59% women) with RIAs, 1176 (44%) were <50 years on
      admission. In people <50 years, the averaged annual mean size of RIAs decreased
      16% from 9.2 mm in 1989 to 1992 to 7.7 mm in 2005 to 2008 in women and 13% (from
      9.3 to 8.1 mm) in men (decreasing linear trend; P=0.001). RIA sizes did not
      change in 50-year-old or older patients, whereas the proportion of posterior
      circulation RIAs almost tripled to 13%, also with a linear relationship
      (P<0.001). CONCLUSIONS: The size of RIAs seems to be decreasing among younger
      generations of hospital-admitted subarachnoid hemorrhage patients, whereas 50
      year-old and older subarachnoid hemorrhage patients have an increasing proportion
      of posterior circulation RIAs. These epidemiological changes are noteworthy,
      especially if they are universal and ongoing.

PMID- 29371433
TI  - Staging Hemodynamic Failure With Blood Oxygen-Level-Dependent Functional Magnetic
      Resonance Imaging Cerebrovascular Reactivity: A Comparison Versus Gold Standard
      (15O-)H2O-Positron Emission Tomography.
AB  - BACKGROUND AND PURPOSE: Increased stroke risk correlates with hemodynamic
      failure, which can be assessed with (15O-)H2O positron emission tomography (PET)
      cerebral blood flow (CBF) measurements. This gold standard technique, however, is
      not established for routine clinical imaging. Standardized blood oxygen-level
      dependent (BOLD) functional magnetic resonance imaging+CO2 is a noninvasive and
      potentially widely applicable tool to assess whole-brain quantitative
      cerebrovascular reactivity (CVR). We examined the agreement between the 2 imaging
      modalities and hypothesized that quantitative CVR can be a surrogate imaging
      marker to assess hemodynamic failure. METHODS: Nineteen data sets of subjects
      with chronic cerebrovascular steno-occlusive disease (age, 60+/-11 years; 4
      women) and unilaterally impaired perfusion reserve on Diamox-challenged (15O-)H2O
      PET were studied and compared with a standardized BOLD functional magnetic
      resonance imaging+CO2 examination within 6 weeks (8+/-19 days). Agreement between
      quantitative CBF- and CVR-based perfusion reserve was assessed. Hemodynamic
      failure was staged according to PET findings: stage 0: normal CBF, normal
      perfusion reserve; stage I: normal CBF, decreased perfusion reserve; and stage
      II: decreased CBF, decreased perfusion reserve. The BOLD CVR data set of the same
      subjects was then matched to the corresponding stage of hemodynamic failure.
      RESULTS: PET-based stage I versus stage II could also be clearly separated with
      BOLD CVR measurements (CVR for stage I 0.11 versus CVR for stage II -0.03;
      P<0.01). Hemispheric and middle cerebral artery territory difference analyses
      (ie, affected versus unaffected side) showed a significant correlation for CVR
      impairment in the affected hemisphere and middle cerebral artery territory
      (P<0.01, R2=0.47 and P=0.02, R2= 0.25, respectively). CONCLUSIONS: BOLD CVR
      corresponded well to CBF perfusion reserve measurements obtained with (15O-)H2O
      PET, especially for detecting hemodynamic failure in the affected hemisphere and
      middle cerebral artery territory and for identifying hemodynamic failure stage
      II. BOLD CVR may, therefore, be considered for prospective studies assessing
      stroke risk in patients with chronic cerebrovascular steno-occlusive disease, in
      particular because it can potentially be implemented in routine clinical imaging.

PMID- 29371435
TI  - Vagus Nerve Stimulation Enhances Stable Plasticity and Generalization of Stroke
      Recovery.
AB  - BACKGROUND AND PURPOSE: Chronic impairment of the arm and hand is a common
      consequence of stroke. Animal and human studies indicate that brief bursts of
      vagus nerve stimulation (VNS) in conjunction with rehabilitative training improve
      recovery of motor function after stroke. In this study, we tested whether VNS
      could promote generalization, long-lasting recovery, and structural plasticity in
      motor networks. METHODS: Rats were trained on a fully automated, quantitative
      task that measures forelimb supination. On task proficiency, unilateral cortical
      and subcortical ischemic lesions were administered. One week after ischemic
      lesion, rats were randomly assigned to receive 6 weeks of rehabilitative training
      on the supination task with or without VNS. Rats then underwent 4 weeks of
      testing on a task assessing forelimb strength to test generalization of recovery.
      Finally, the durability of VNS benefits was tested on the supination task 2
      months after the cessation of VNS. After the conclusion of behavioral testing,
      viral tracing was performed to assess synaptic connectivity in motor networks.
      RESULTS: VNS enhances plasticity in corticospinal motor networks to increase
      synaptic connectivity to musculature of the rehabilitated forelimb. Adding VNS
      more than doubled the benefit of rehabilitative training, and the improvements
      lasted months after the end of VNS. Pairing VNS with supination training also
      significantly improved performance on a similar, but untrained task that
      emphasized volitional forelimb strength, suggesting generalization of forelimb
      recovery. CONCLUSIONS: This study provides the first evidence that VNS paired
      with rehabilitative training after stroke (1) doubles long-lasting recovery on a
      complex task involving forelimb supination, (2) doubles recovery on a simple
      motor task that was not paired with VNS, and (3) enhances structural plasticity
      in motor networks.

PMID- 29371434
TI  - Oxidative Stress Biomarkers of Brain Damage: Hyperacute Plasma F2-Isoprostane
      Predicts Infarct Growth in Stroke.
AB  - BACKGROUND AND PURPOSE: Oxidative stress is an early response to cerebral
      ischemia and is likely to play an important role in the pathogenesis of cerebral
      ischemic injury. We sought to evaluate whether hyperacute plasma concentrations
      of biomarkers of oxidative stress, inflammation, and tissue damage predict
      infarct growth (IG). METHODS: We prospectively measured plasma F2-isoprostane (F2
      isoP), urinary 8-oxo-7,8-dihydro-2'-deoxyguoanosine, plasma oxygen radical
      absorbance capacity assay, high sensitivity C reactive protein, and matrix
      metalloproteinase 2 and 9 in consecutive patients with acute ischemic stroke
      presenting within 9 hours of symptom onset. Patients with baseline diffusion
      weighted magnetic resonance imaging and follow-up diffusion-weighted imaging or
      computed tomographic scan were included to evaluate the final infarct volume.
      Baseline diffusion-weighted imaging volume and final infarct volume were analyzed
      using semiautomated volumetric method. IG volume was defined as the difference
      between final infarct volume and baseline diffusion-weighted imaging volume.
      RESULTS: A total of 220 acute ischemic stroke subjects were included in the final
      analysis. One hundred seventy of these had IG. Baseline F2-isoP significantly
      correlated with IG volume (Spearman rho=0.20; P=0.005) and final infarct volume
      (Spearman rho=0.19; P=0.009). In a multivariate binary logistic regression model,
      baseline F2-isoP emerged as an independent predictor of the occurrence of IG
      (odds ratio, 2.57; 95% confidence interval, 1.37-4.83; P=0.007). In a
      multivariate linear regression model, baseline F2-isoP was independently
      associated with IG volume (B, 0.38; 95% confidence interval, 0.04-0.72; P=0.03).
      CONCLUSIONS: Elevated hyperacute plasma F2-isoP concentrations independently
      predict the occurrence of IG and IG volume in patients with acute ischemic
      stroke. If validated in future studies, measuring plasma F2-isoP might be helpful
      in the acute setting to stratify patients with acute ischemic stroke for relative
      severity of ischemic injury and expected progression.

PMID- 29371437
TI  - A Novel Class of Histone Readers.

PMID- 29371436
TI  - Relationship Between Visceral Infarction and Ischemic Stroke Subtype.
AB  - BACKGROUND AND PURPOSE: Most cryptogenic strokes are thought to have an embolic
      source. We sought to determine whether cryptogenic strokes are associated with
      visceral infarcts, which are usually embolic. METHODS: Among patients
      prospectively enrolled in CAESAR (Cornell Acute Stroke Academic Registry), we
      selected those with a contrast-enhanced abdominal computed tomographic scan
      within 1 year of admission. Our exposure variable was adjudicated stroke subtype
      per the Trial of ORG 10172 in Acute Stroke Treatment classification. Our outcome
      was renal or splenic infarction as assessed by a single radiologist blinded to
      stroke subtype. We used Fisher exact test and multiple logistic regression to
      compare the prevalence of visceral infarcts among cardioembolic strokes, strokes
      of undetermined etiology, and noncardioembolic strokes (large- or small-vessel
      strokes). RESULTS: Among 227 patients with ischemic stroke and a contrast
      enhanced abdominal computed tomographic scan, 59 had a visceral infarct (35 renal
      and 27 splenic). The prevalence of visceral infarction was significantly
      different among cardioembolic strokes (34.2%; 95% confidence interval [CI], 23.7%
      44.6%), strokes of undetermined etiology (23.9%; 95% CI, 15.0%-32.8%), and
      strokes from large-artery atherosclerosis or small-vessel occlusion (12.5%; 95%
      CI, 1.8%-23.2%; P=0.03). In multiple logistic regression models adjusted for
      demographics and vascular comorbidities, we found significant associations with
      visceral infarction for both cardioembolic stroke (odds ratio, 3.5; 95% CI, 1.2
      9.9) and stroke of undetermined source (odds ratio, 3.3; 95% CI, 1.1-10.5) as
      compared with noncardioembolic stroke. CONCLUSIONS: The prevalence of visceral
      infarction differed significantly across ischemic stroke subtypes. Cardioembolic
      and cryptogenic strokes were associated with a higher prevalence of visceral
      infarcts than noncardioembolic strokes.

PMID- 29371438
TI  - AUXIN RESPONSE FACTOR3 Regulates Floral Meristem Determinacy by Repressing
      Cytokinin Biosynthesis and Signaling.
AB  - Successful floral meristem (FM) determinacy is critical for subsequent
      reproductive development and the plant life cycle. Although the phytohormones
      cytokinin and auxin interact to coregulate many aspects of plant development,
      whether and how cytokinin and auxin function in FM determinacy remain unclear.
      Here, we show that in Arabidopsis thaliana, cytokinin homeostasis is critical for
      FM determinacy. In this developmental context, auxin promotes the expression of
      AUXIN RESPONSE FACTOR3 (ARF3) to repress cytokinin activity. ARF3 directly
      represses the expression of ISOPENTENYLTRANSFERASE (IPT) family genes and
      indirectly represses LONELY GUY (LOG) family genes, both of which encode enzymes
      required for cytokinin biosynthesis. ARF3 also directly inhibits the expression
      of ARABIDOPSIS HISTIDINE KINASE4, a cytokinin receptor gene, resulting in reduced
      cytokinin activity. Consequently, ARF3 controls cell division by regulating cell
      cycle gene expression through cytokinin. In flowers, we show that AGAMOUS (AG)
      dynamically regulates the expression of ARF3 and IPTs, resulting in coordinated
      regulation of FM maintenance and termination through cell division. Moreover,
      genome-wide transcriptional profiling revealed both repressive and active roles
      for ARF3 in early flower development. Our findings establish a molecular link
      between AG and auxin/cytokinin and shed light on the mechanisms of stem cell
      maintenance and termination in the FM.

PMID- 29371441
TI  - Comment on "Precipitation drives global variation in natural selection".
AB  - Siepielski et al (Reports, 3 March 2017, p. 959) claim that "precipitation drives
      global variation in natural selection." This conclusion is based on a meta
      analysis of the relationship between climate variables and natural selection
      measured in wild populations of invertebrates, plants, and vertebrates. Three
      aspects of this analysis cause concern: (i) lack of within-year climate
      variables, (ii) low and variable estimates of covariance relationships across
      taxa, and (iii) a lack of mechanistic explanations for the patterns observed;
      association is not causation.

PMID- 29371439
TI  - The Biotrophic Development of Ustilago maydis Studied by RNA-Seq Analysis.
AB  - The maize smut fungus Ustilago maydis is a model organism for elucidating host
      colonization strategies of biotrophic fungi. Here, we performed an in depth
      transcriptional profiling of the entire plant-associated development of U. maydis
      wild-type strains. In our analysis, we focused on fungal metabolism, nutritional
      strategies, secreted effectors, and regulatory networks. Secreted proteins were
      enriched in three distinct expression modules corresponding to stages on the
      plant surface, establishment of biotrophy, and induction of tumors. These modules
      are likely the key determinants for U. maydis virulence. With respect to nutrient
      utilization, we observed that expression of several nutrient transporters was
      tied to these virulence modules rather than being controlled by nutrient
      availability. We show that oligopeptide transporters likely involved in nitrogen
      assimilation are important virulence factors. By measuring the intramodular
      connectivity of transcription factors, we identified the potential drivers for
      the virulence modules. While known components of the b-mating type cascade
      emerged as inducers for the plant surface and biotrophy module, we identified a
      set of yet uncharacterized transcription factors as likely responsible for
      expression of the tumor module. We demonstrate a crucial role for leaf tumor
      formation and effector gene expression for one of these transcription factors.

PMID- 29371440
TI  - Spermidine in health and disease.
AB  - Interventions that delay aging and protect from age-associated disease are slowly
      approaching clinical implementation. Such interventions include caloric
      restriction mimetics, which are defined as agents that mimic the beneficial
      effects of dietary restriction while limiting its detrimental effects. One such
      agent, the natural polyamine spermidine, has prominent cardioprotective and
      neuroprotective effects and stimulates anticancer immunosurveillance in rodent
      models. Moreover, dietary polyamine uptake correlates with reduced cardiovascular
      and cancer-related mortality in human epidemiological studies. Spermidine
      preserves mitochondrial function, exhibits anti-inflammatory properties, and
      prevents stem cell senescence. Mechanistically, it shares the molecular pathways
      engaged by other caloric restriction mimetics: It induces protein deacetylation
      and depends on functional autophagy. Because spermidine is already present in
      daily human nutrition, clinical trials aiming at increasing the uptake of this
      polyamine appear feasible.

PMID- 29371443
TI  - A tale of two cultures.

PMID- 29371442
TI  - Response to Comment on "Precipitation drives global variation in natural
      selection".
AB  - The comment by Myers-Smith and Myers focuses on three main points: (i) the lack
      of a mechanistic explanation for climate-selection relationships, (ii) the
      appropriateness of the climate data used in our analysis, and (iii) our focus on
      estimating climate-selection relationships across (rather than within) taxonomic
      groups. We address these critiques in our response.

PMID- 29371444
TI  - News at a glance.

PMID- 29371445
TI  - Critics see only risks, no benefits in horsepox paper.

PMID- 29371446
TI  - Heavy-lift rocket poised to boost space science.

PMID- 29371447
TI  - In thousands of brain scans, group seeks clues to diseases.

PMID- 29371448
TI  - Crackdown threatens science in Turkey.

PMID- 29371449
TI  - Australian state forecasts deadly thunderstorm asthma.

PMID- 29371450
TI  - Muon's magnetism could point to new physics.

PMID- 29371451
TI  - The light fantastic.

PMID- 29371452
TI  - Using nature to understand nurture.

PMID- 29371453
TI  - Perovskite solar cells must come of age.

PMID- 29371454
TI  - When did modern humans leave Africa?

PMID- 29371455
TI  - Complexity in targeting membrane proteins.

PMID- 29371456
TI  - Conserving honey bees does not help wildlife.

PMID- 29371457
TI  - Toward a silicon-based quantum computer.

PMID- 29371458
TI  - Engaging over data on fracking and water quality.

PMID- 29371459
TI  - Conscious machines: Defining questions.

PMID- 29371460
TI  - Conscious machines: Robot rights.

PMID- 29371461
TI  - Response.

PMID- 29371462
TI  - Substantial convection and precipitation enhancements by ultrafine aerosol
      particles.
AB  - Aerosol-cloud interactions remain the largest uncertainty in climate projections.
      Ultrafine aerosol particles smaller than 50 nanometers (UAP<50) can be abundant
      in the troposphere but are conventionally considered too small to affect cloud
      formation. Observational evidence and numerical simulations of deep convective
      clouds (DCCs) over the Amazon show that DCCs forming in a low-aerosol environment
      can develop very large vapor supersaturation because fast droplet coalescence
      reduces integrated droplet surface area and subsequent condensation. UAP<50 from
      pollution plumes that are ingested into such clouds can be activated to form
      additional cloud droplets on which excess supersaturation condenses and forms
      additional cloud water and latent heating, thus intensifying convective strength.
      This mechanism suggests a strong anthropogenic invigoration of DCCs in previously
      pristine regions of the world.

PMID- 29371463
TI  - The nature of nurture: Effects of parental genotypes.
AB  - Sequence variants in the parental genomes that are not transmitted to a child
      (the proband) are often ignored in genetic studies. Here we show that
      nontransmitted alleles can affect a child through their impacts on the parents
      and other relatives, a phenomenon we call "genetic nurture." Using results from a
      meta-analysis of educational attainment, we find that the polygenic score
      computed for the nontransmitted alleles of 21,637 probands with at least one
      parent genotyped has an estimated effect on the educational attainment of the
      proband that is 29.9% (P = 1.6 * 10-14) of that of the transmitted polygenic
      score. Genetic nurturing effects of this polygenic score extend to other traits.
      Paternal and maternal polygenic scores have similar effects on educational
      attainment, but mothers contribute more than fathers to nutrition- and heath
      related traits.

PMID- 29371464
TI  - A platform for automated nanomole-scale reaction screening and micromole-scale
      synthesis in flow.
AB  - The scarcity of complex intermediates in pharmaceutical research motivates the
      pursuit of reaction optimization protocols on submilligram scales. We report here
      the development of an automated flow-based synthesis platform, designed from
      commercially available components, that integrates both rapid nanomole-scale
      reaction screening and micromole-scale synthesis into a single modular unit. This
      system was validated by exploring a diverse range of reaction variables in a
      Suzuki-Miyaura coupling on nanomole scale at elevated temperatures, generating
      liquid chromatography-mass spectrometry data points for 5760 reactions at a rate
      of >1500 reactions per 24 hours. Through multiple injections of the same segment,
      the system directly produced micromole quantities of desired material. The
      optimal conditions were also replicated in traditional flow and batch mode at 50-
      to 200-milligram scale to provide good to excellent yields.

PMID- 29371465
TI  - Synthesis of partially and fully fused polyaromatics by annulative
      chlorophenylene dimerization.
AB  - Since the discovery by Ullmann and Bielecki in 1901, reductive dimerization (or
      homocoupling) of aryl halides has been extensively exploited for the generation
      of a range of biaryl-based functional molecules. In contrast to the single-point
      connection in these products, edge-sharing fused aromatic systems have not
      generally been accessible from simple aryl halides via annulation cascades. Here
      we report a single-step synthesis of fused aromatics with a triphenylene core by
      the palladium-catalyzed annulative dimerization of structurally and functionally
      diverse chlorophenylenes through double carbon-hydrogen bond activation. The
      partially fused polyaromatics can be transformed into fully fused, small graphene
      nanoribbons, which are otherwise difficult to synthesize. This simple, yet
      powerful, method allows access to functional pi-systems of interest in
      optoelectronics research.

PMID- 29371466
TI  - Nanoscale chiral valley-photon interface through optical spin-orbit coupling.
AB  - The emergence of two-dimensional transition metal dichalcogenide materials has
      sparked intense activity in valleytronics, as their valley information can be
      encoded and detected with the spin angular momentum of light. We demonstrate the
      valley-dependent directional coupling of light using a plasmonic nanowire
      tungsten disulfide (WS2) layers system. We show that the valley pseudospin in WS2
      couples to transverse optical spin of the same handedness with a directional
      coupling efficiency of 90 +/- 1%. Our results provide a platform for controlling,
      detecting, and processing valley and spin information with precise optical
      control at the nanoscale.

PMID- 29371467
TI  - Mechanistic origin and prediction of enhanced ductility in magnesium alloys.
AB  - Pure magnesium exhibits poor ductility owing to pyramidal [Formula: see text]
      dislocation transformations to immobile structures, making this lowest-density
      structural metal unusable for many applications where it could enhance energy
      efficiency. We show why magnesium can be made ductile by specific dilute solute
      additions, which increase the [Formula: see text] cross-slip and multiplication
      rates to levels much faster than the deleterious [Formula: see text]
      transformation, enabling both favorable texture during processing and continued
      plastic straining during deformation. A quantitative theory establishes the
      conditions for ductility as a function of alloy composition in very good
      agreement with experiments on many existing magnesium alloys, and the solute
      enhanced cross-slip mechanism is confirmed by transmission electron microscopy
      observations in magnesium-yttrium. The mechanistic theory can quickly screen for
      alloy compositions favoring conditions for high ductility and may help in the
      development of high-formability magnesium alloys.

PMID- 29371469
TI  - Plastic waste associated with disease on coral reefs.
AB  - Plastic waste can promote microbial colonization by pathogens implicated in
      outbreaks of disease in the ocean. We assessed the influence of plastic waste on
      disease risk in 124,000 reef-building corals from 159 reefs in the Asia-Pacific
      region. The likelihood of disease increases from 4% to 89% when corals are in
      contact with plastic. Structurally complex corals are eight times more likely to
      be affected by plastic, suggesting that microhabitats for reef-associated
      organisms and valuable fisheries will be disproportionately affected. Plastic
      levels on coral reefs correspond to estimates of terrestrial mismanaged plastic
      waste entering the ocean. We estimate that 11.1 billion plastic items are
      entangled on coral reefs across the Asia-Pacific and project this number to
      increase 40% by 2025. Plastic waste management is critical for reducing diseases
      that threaten ecosystem health and human livelihoods.

PMID- 29371468
TI  - The earliest modern humans outside Africa.
AB  - To date, the earliest modern human fossils found outside of Africa are dated to
      around 90,000 to 120,000 years ago at the Levantine sites of Skhul and Qafzeh. A
      maxilla and associated dentition recently discovered at Misliya Cave, Israel, was
      dated to 177,000 to 194,000 years ago, suggesting that members of the Homo
      sapiens clade left Africa earlier than previously thought. This finding changes
      our view on modern human dispersal and is consistent with recent genetic studies,
      which have posited the possibility of an earlier dispersal of Homo sapiens around
      220,000 years ago. The Misliya maxilla is associated with full-fledged Levallois
      technology in the Levant, suggesting that the emergence of this technology is
      linked to the appearance of Homo sapiens in the region, as has been documented in
      Africa.

PMID- 29371470
TI  - Learning and attention reveal a general relationship between population activity
      and behavior.
AB  - Prior studies have demonstrated that correlated variability changes with
      cognitive processes that improve perceptual performance. We tested whether
      correlated variability covaries with subjects' performance-whether performance
      improves quickly with attention or slowly with perceptual learning. We found a
      single, consistent relationship between correlated variability and behavioral
      performance, regardless of the time frame of correlated variability change. This
      correlated variability was oriented along the dimensions in population space used
      by the animal on a trial-by-trial basis to make decisions. That subjects' choices
      were predicted by specific dimensions that were aligned with the correlated
      variability axis clarifies long-standing paradoxes about the relationship between
      shared variability and behavior.

PMID- 29371472
TI  - Cheating on my mentor.

PMID- 29371473
TI  - Single Arm, Phase II Study of Cisplatin, Docetaxel, and Erlotinib in Patients
      with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinomas.
AB  - LESSONS LEARNED: The combination of cisplatin, docetaxel, and erlotinib as
      frontline treatment for recurrent and/or metastatic head and neck squamous cell
      carcinomas led to a response rate of 62%.This result exceeded the prespecified
      target response rate of 50% and represented an improvement compared with
      historical controls.This regimen warrants further investigation. BACKGROUND: The
      epidermal growth factor receptor (EGFR) plays a key role in the carcinogenesis of
      head and neck squamous cell carcinomas (HNSCC). We conducted this clinical study
      to test the hypothesis that the addition of erlotinib to first-line cisplatin and
      docetaxel for patients with recurrent and/or metastatic HNSCC would yield a
      response rate of at least 50%, representing an improvement from historical
      controls. METHODS: Patients with recurrent and/or metastatic HNSCC, with at least
      one measurable lesion, no prior chemotherapy for recurrent and/or metastatic
      disease, prior combined modality therapy completed >6 months before enrollment,
      and performance status <=2 were treated with cisplatin, docetaxel, and erlotinib
      for up to six cycles, followed by maintenance erlotinib until disease
      progression. The primary endpoint was response rate. RESULTS: Fifty patients were
      enrolled (42 male, 12 never smokers, 19 with oropharynx cancer). The median
      number of cycles was five; 31 patients initiated maintenance erlotinib; 14
      patients required erlotinib dose reductions. The objective response rate was 62%,
      and the median progression-free and overall survival were 6.1 and 11.0 months,
      respectively. Toxicity profiles were consistent with the known side effects of
      the study drugs. CONCLUSION: The study met its primary endpoint and improved
      response rates compared with historical controls. The findings support further
      evaluation of the regimen for recurrent and/or metastatic HNSCCs.

PMID- 29371474
TI  - Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer
      Monitoring.
AB  - BACKGROUND: Many new pancreatic cancer treatment combinations have been
      discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma
      (PDAC) remains grim. The advent of new treatments highlights the need for better
      monitoring tools for treatment response, to allow a timely switch between
      different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for
      cancer detection and characterization with growing clinical use. However,
      currently, ctDNA is not used for monitoring treatment response. The high
      prevalence of KRAS hotspot mutations in PDAC suggests that mutant KRAS can be an
      efficient ctDNA marker for PDAC monitoring. SUBJECTS, MATERIALS, AND METHODS:
      Seventeen metastatic PDAC patients were recruited and serial plasma samples were
      collected. CtDNA was extracted from the plasma, and KRAS mutation analysis was
      performed using next-generation sequencing and correlated with serum CA19-9
      levels, imaging, and survival. RESULTS: Plasma KRAS mutations were detected in
      5/17 (29.4%) patients. KRAS ctDNA detection was associated with shorter survival
      (8 vs. 37.5 months). Our results show that, in ctDNA positive patients, ctDNA is
      at least comparable to CA19-9 as a marker for monitoring treatment response.
      Furthermore, the rate of ctDNA change was inversely correlated with survival.
      CONCLUSION: Our results confirm that mutant KRAS ctDNA detection in metastatic
      PDAC patients is a poor prognostic marker. Additionally, we were able to show
      that mutant KRAS ctDNA analysis can be used to monitor treatment response in PDAC
      patients and that ctDNA dynamics is associated with survival. We suggest that
      ctDNA analysis in metastatic PDAC patients is a readily available tool for
      disease monitoring. IMPLICATIONS FOR PRACTICE: Avoiding futile chemotherapy in
      metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring
      response to treatment is of utmost importance. A novel biomarker for monitoring
      treatment response in PDAC, using mutant KRAS circulating tumor DNA (ctDNA), is
      proposed. Results, although limited by small sample numbers, suggest that ctDNA
      can be an effective marker for disease monitoring and that ctDNA level over time
      is a better predictor of survival than the dynamics of the commonly used
      biomarker CA19-9. Therefore, ctDNA analysis can be a useful tool for monitoring
      PDAC treatment response. These results should be further validated in larger
      sample numbers.

PMID- 29371475
TI  - Chemoprevention in Patients with Peutz-Jeghers Syndrome: Lessons Learned.
AB  - LESSONS LEARNED: Motivating patients to enroll in chemopreventive studies is
      challenging.Chemoprevention with toxic drugs is not feasible. BACKGROUND: LKB1
      mutations are the underlying genetic abnormality causing Peutz-Jeghers syndrome
      (PJS) and are a potential target for everolimus. In this phase II study, the
      efficacy of everolimus on polyp and tumor growth in PJS patients was
      investigated. METHODS: Adult patients with a proven LKB1 mutation and who were
      suitable for everolimus treatment were included in two different PJS cohorts: (a)
      patients with unresectable malignancies and (b) patients with high-risk polyps.
      Treatment in both groups was oral everolimus, 10 mg daily. Response rates were
      primary endpoints for both cohorts. RESULTS: Between October 2011 and April 2016,
      only two patients were enrolled, one in each cohort. A 49-year-old patient with
      advanced pancreatic cancer in cohort 1 was progressive after 2 months. A 52-year
      old male patient in cohort 2 experienced severe toxicity and refused treatment
      after 4 months, even though endoscopy suggested stabilization of polyps. Adverse
      events included dental inflammations, mucositis, and rash. In 2016, the trial was
      aborted for lack of accrual, despite extensive accrual efforts in an area where
      PJS is highly prevalent and care is highly centralized. CONCLUSION: Due to
      accrual problems, no conclusions can be drawn about the value of everolimus in
      PJS treatment, questioning the feasibility of this agent for chemoprevention.

PMID- 29371476
TI  - Prospective Evaluation of the Impact of the 21-Gene Recurrence Score Assay on
      Adjuvant Treatment Decisions for Women with Node-Positive Breast Cancer in
      Ontario, Canada.
AB  - BACKGROUND: The 21-gene Recurrence Score (RS) assay is only reimbursed in Ontario
      for node-negative and micrometastatic node-positive (N+) early-stage breast
      cancer (EBC). We carried out a prospective study to evaluate the impact of the
      assay on treatment decisions for women with N+ EBC. SUBJECTS, MATERIALS, AND
      METHODS: Women with estrogen receptor-positive, human epidermal growth receptor 2
      negative EBC and one to three positive axillary lymph nodes, who were candidates
      for adjuvant chemotherapy in addition to hormonal treatment, but in whom the
      benefit of chemotherapy was uncertain, were eligible. The primary objective was
      to characterize how the results of the RS assay affected physicians'
      recommendations for adjuvant chemotherapy. Secondary objectives were to
      characterize changes in the physicians' and patients' level of confidence in
      treatment recommendations, to determine whether the results of the RS assay
      affected patients' treatment preferences, and to determine the final treatment
      administered. RESULTS: Seventy-two patients were recruited; the mean age was 61.
      RS was <18 in 55%, between 18 and 30 in 36%, and >=31 in 9% of patients.
      Treatment recommendations changed in 36% of all evaluable patients. The most
      significant change was in the group with a low RS. Physicians' and patients'
      confidence in treatment recommendations increased in 49% and 54% of cases,
      respectively. Upfront chemotherapy was recommended to 79% of patients before the
      assay; 42% ultimately received chemotherapy. CONCLUSION: The RS assay resulted in
      a substantial decrease in the number of patients who received chemotherapy and in
      an increase in physicians' and patients' confidence in the adjuvant treatment
      recommendations. IMPLICATIONS FOR PRACTICE: This is the first decision impact
      study to include exclusively women with ER-positive, HER2-negative, early-stage
      breast cancer with 1-3 positive lymph nodes, a population typically treated with
      adjuvant chemotherapy. This study provides evidence that, in these patients, the
      Oncotype Dx Recurrence Score assay influences systemic treatment decisions. Most
      of the changes in treatment recommendation resulted in withdrawal of chemotherapy
      or change in recommendation from a chemotherapy regimen with anthracyclines to a
      taxane-only regimen. If prospective studies confirm that these decisions result
      in good outcomes, a reduction in the use of chemotherapy might result in
      pharmacoeconomic savings.

PMID- 29371471
TI  - Moving in the Anthropocene: Global reductions in terrestrial mammalian movements.
AB  - Animal movement is fundamental for ecosystem functioning and species survival,
      yet the effects of the anthropogenic footprint on animal movements have not been
      estimated across species. Using a unique GPS-tracking database of 803 individuals
      across 57 species, we found that movements of mammals in areas with a
      comparatively high human footprint were on average one-half to one-third the
      extent of their movements in areas with a low human footprint. We attribute this
      reduction to behavioral changes of individual animals and to the exclusion of
      species with long-range movements from areas with higher human impact. Global
      loss of vagility alters a key ecological trait of animals that affects not only
      population persistence but also ecosystem processes such as predator-prey
      interactions, nutrient cycling, and disease transmission.

PMID- 29371477
TI  - Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with
      Advanced Solid Tumors.
AB  - BACKGROUND: The decision whether to treat older adults with advanced cancer with
      standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in
      aging. We assessed the potential utility of the chemotherapy toxicity risk score
      (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults.
      MATERIALS AND METHODS: This was a prospective observational study of patients
      aged >=65 years receiving first-line chemotherapy for advanced cancer for which
      combination chemotherapy is the standard of care. Patients were categorized as
      high risk (CTRS >=10), for whom RT (dose-reduced combination or single-agent
      chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is
      deemed appropriate for toxicity. The primary objective was to estimate the
      agreement in chemotherapy choice (ST vs. RT) between the treating physician and
      the CTRS using a kappa statistic. RESULTS: Fifty-eight patients (median age, 71
      years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17
      had CTRS >=10), and 20 patients received RT (12 had CTRS >=10, and 8 had CTRS
      <10), with minimal agreement in chemotherapy choice (kappa = 0.14; 95% CI, -0.10
      to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55
      patients with follow-up data, respectively. Among patients receiving ST, patients
      with CTRS >=10 had a higher incidence of toxicity (88% vs. 40%, p = .006) and
      hospitalization (50% vs. 15%, p = .03) than those with CTRS <10. CONCLUSION:
      Older patients with cancer with a high CTRS who receive combination chemotherapy
      have an exceedingly high rate of severe toxicity and hospitalization.
      IMPLICATIONS FOR PRACTICE: The potential utility of the chemotherapy toxicity
      risk score (CTRS) in old adults with advanced solid tumors receiving first-line
      chemotherapy was assessed. Little agreement was found between chemotherapy
      treatment decisions based on the clinical impression versus what was recommended
      based on the CTRS. Among patients treated with standard-dose combination
      chemotherapy, patients with CTRS >=10 had a very high incidence of grade 3-4
      toxicities and hospitalization, which was significantly greater than that of
      patients with a low CTRS (<10). These findings suggest that the addition of CTRS
      to the clinical impression has a potential to improve treatment decisions.

PMID- 29371478
TI  - Serious Illness Conversations: Paving the Road with Metaphors.
AB  - : Serious illness conversations can influence the direction of care by supporting
      decision-making compatible with the patient's goals. Effective use of core
      communication techniques, such as active listening and empathic statements,
      allows for a deeper understanding of the patients' goals, concerns, communication
      preferences, and questions. Metaphors can be used to augment end-of-life care
      planning. Used inappropriately, metaphors can cause misunderstandings and
      confusion. Applied skillfully, metaphors can personalize challenging discussions,
      improving patient comprehension and helping patients and their families to plan
      ahead. The art of communication is to use the right tool for the right person at
      the right time. IMPLICATIONS FOR PRACTICE: Discussions with patients about
      serious illness concerns are especially challenging for the oncologist. This
      article provides guidance for preparing for such conversations, including
      examples of the use of metaphors to personalize and improve communication.

PMID- 29371479
TI  - EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple
      Myeloma.
AB  - : On May 20, 2016, a conditional marketing authorization valid through the
      European Union (EU) was issued for daratumumab as monotherapy for the treatment
      of adult patients with relapsed and refractory multiple myeloma, whose prior
      therapy included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
      and who had demonstrated disease progression on the last therapy. The review of
      daratumumab was conducted under the EMA's accelerated assessment program for
      drugs that are of major interest for public health, especially from the point of
      view of therapeutic innovation.Daratumumab monotherapy achieved an overall
      response rate of 29.2% (95% confidence interval [CI] 20.8 to 38.9) in patients
      with multiple myeloma who had received at least three prior lines of therapy
      (including a PI and IMiD) or were double refractory to a PI and an IMiD (Study
      MMY2002). In patients with multiple myeloma relapsed from or refractory to two or
      more different prior therapies, including IMiDs (e.g., thalidomide, lenalidomide)
      and PI, an overall response was observed in 15 patients (35.7%, 95% CI: 21.6 to
      52.0) (Study GEN501).On April 28, 2017, the therapeutic indication was extended
      to include the use of daratumumab in combination with lenalidomide and
      dexamethasone, or bortezomib and dexamethasone, for the treatment of adult
      patients with multiple myeloma who have received at least one prior therapy. This
      was based on two subsequent phase III studies of daratumumab in combination with
      lenalidomide/low-dose dexamethasone (MMY3003) and bortezomib/low dose
      dexamethasone (MMY3004).The most common side effects (grade 3-4) associated with
      daratumumab included neutropenia (37%), thrombocytopenia (23%), anemia (16%),
      pneumonia (10%), lymphopenia (8%), infusion-related reactions (6%), upper
      respiratory tract infection (5%), and fatigue (5%).The objective of this study
      was to summarize the scientific review done by the CHMP of the application
      leading to regulatory approval in the EU. The full scientific assessment report
      and product information, including the Summary of Product Characteristics (SmPC),
      are available on the EMA website (www.ema.europa.eu). IMPLICATIONS FOR PRACTICE:
      A conditional Marketing authorization was issued in the European Union for
      daratumamb as monotherapy for the treatment of adult patients with relapsed and
      refractory multiple myeloma, based on the response rate data from two single
      agent studies. Darzalex, a novel monoclonal antibody targeted against CD38,
      demonstrated a durable response rate in a heavily pre-treated population with
      limited treatment options based on the response rate data from two single-agent
      studies. The addition of daratumumab to lenalidomide and dexamethasone (study
      MMY3003), or bortezomib and dexamethasone (MMY3004), demonstrated a positive
      effect on progression-free survival in patients with multiple myeloma who had
      received at least one prior therapy. Following submission of the controlled data
      of the MMY3003 and MMY3004 studies, the efficacy and safety of daratumumab was
      confirmed and the approval of daratumumab was converted to standard approval.

PMID- 29371480
TI  - [Development of intravital bone tissue imaging and future perspectives of new
      lines of therapies for bone diseases.]
AB  - Recent advances in live imaging technology for 'seeing the unseen' phenomenon has
      been so enormous to revolutionize the diverse fields of biomedical sciences. We
      have so far pioneered to exploit the technique into the analyses of live bone
      tissues and made it possible to detect dynamic movements of single cells and
      multicellular interaction in intact bone tissues. Now that the cutting-edge
      techniques have been matured enough, we can also utilize this for validation of
      pharmacological actions in various regimens in vivo as well as for novel drug
      discovery for treating against bone diseases. In this brief review, I describe
      the overview of the studies related to intravital bone imaging and its
      application and contribution for future medicine in this field.

PMID- 29371481
TI  - [Basis of intravital bone imaging.]
AB  - In bone tissues, there are various kinds of cell types, such as osteoclasts,
      osteoblasts, monocytes, granulocyte, lymphocytes, mesenchymal cells and
      hematopoietic stem cells. They form a network with each other, and play critical
      roles in our life activities. The recent development of intravital two-photon
      imaging has enabled us to visualize the in vivo behavior of bone marrow cells in
      living bone tissues. This technique facilitates investigation of cellular
      dynamics in the physiology and pathogenesis of bone disorders in vivo, and would
      thus be useful for evaluating the efficacy of novel drugs. In this review, we
      summarize the basis of intravital bone imaging, and also discuss its further
      application.

PMID- 29371482
TI  - [Development of methodology for living bone imaging.]
AB  - Bone tissue consist of a wide variety of cells such as osteoclasts, osteoblasts
      and osteocytes which are involved in bone metabolism, hematopoietic cells which
      can differentiate and mature in the bone marrow, other mesenchymal cells and
      nerve cells. Recent advances in "fluorescent imaging technology" have made it
      possible to observe bone tissue alive. And intravital imaging enable us not only
      to examine the "morphology" but also to analyze the "dynamics" of the cells. We
      have improved "two-photon microscope" which can observe deep tissue with
      minimally invasive manner and have established an imaging method to observe the
      movement of cells in living bone tissue in real time. In this review, we
      summarize the methodology of intravital imaging, such as the principle of two
      photon excitation microscope, method of in vivo imaging of bone, and analysis of
      acquired imaging data.

PMID- 29371483
TI  - [Development of fluorescent probes for bone imaging in vivo ~Fluorescent probes
      for intravital imaging of osteoclast activity~.]
AB  - Fluorescent molecules are widely used as a tool to directly visualize target
      biomolecules in vivo. Fluorescent probes have the advantage that desired function
      can be rendered based on rational design. For bone-imaging fluorescent probes in
      vivo, they should be delivered to bone tissue upon administration. Recently, a
      fluorescent probe for detecting osteoclast activity was developed. The
      fluorescent probe has acid-sensitive fluorescence property, specific delivery to
      bone tissue, and durability against laser irradiation, which enabled real-time
      intravital imaging of bone-resorbing osteoclasts for a long period of time.

PMID- 29371484
TI  - [Quantitative data analysis for live imaging of bone.]
AB  - Bone tissue is a hard tissue, it was difficult to observe the interior of the
      bone tissue alive. With the progress of microscopic technology and fluorescent
      probe technology in recent years, it becomes possible to observe various
      activities of various cells forming bone society. On the other hand, the
      quantitative increase in data and the diversification and complexity of the
      images makes it difficult to perform quantitative analysis by visual inspection.
      It has been expected to develop a methodology for processing microscopic images
      and data analysis. In this article, we introduce the research field of bioimage
      informatics which is the boundary area of biology and information science, and
      then outline the basic image processing technology for quantitative analysis of
      live imaging data of bone.

PMID- 29371485
TI  - [Generation of Mice Carrying Reporter for live bone imaging.]
AB  - Fluorescence imaging technology using two-photon excitation microscopy has been
      developed and utilized to observe cell dynamics in various developmental
      processes and pathological conditions in vivo. This technology is absolutely
      dependent on the fluorescent labelling technique of specific cells in a living
      state in vivo using various methods such as genetic engineering, chemiluminescent
      probes or fluorescent-conjugated antibodies. In this article, we demonstrate the
      methods of genetic engineering, particularly how to generate a genetically
      modified mouse(reporter mouse)that expresses fluorescent protein endogenously in
      the specific cells. In consideration of mouse genetic engineering technologies
      and the current state of bioresources, we describe the transgenic method, the
      knock-in method, the Cre/loxP-mediated recombination method and the genomic
      editing method by CRISPR/Cas9 system that have been used widely for generation of
      reporter mice. Among these methods, it is important to carefully select the
      suitable method according to the research purpose. We would like to compare the
      methods comprehensively.

PMID- 29371486
TI  - [Intravital bone imaging:osteoclast.]
AB  - Osteoclasts are bone-resorbing giant polykaryons that differentiate from
      mononuclear macrophage/monocyte-lineage hematopoietic precursors. We have
      originally established an advanced imaging system for visualizing the in vivo
      behavior of mature osteoclasts in living bone tissues with intravital multiphoton
      microscopy. By means of this system, we could grasp the real time-course of
      osteoclastic bone resorption, and identified two distinct functional states of
      differentiated osteoclasts, 'bone-resorptive' and 'non-resorptive'. Intravital
      imaging also revealed that various biologic drugs acted directly on mature
      osteoclasts during inflammatory bone destruction. In this review, we show the
      latest data of intravital imaging of osteoclast dynamics.

PMID- 29371487
TI  - [In vivo imaging of osteoblasts.]
AB  - Osteoblasts are bone-forming cells which produce bone matrix proteins and control
      calcium and mineral deposition. It is still unknown how osteoblasts work through
      the processes actually, because most of bone researches use static images of
      sections. Recently developed intravital imaging system with multiphoton
      microscopy can enable dynamic observation of living individual cells without
      making sections. This technique has so high-resolution in the Z direction that it
      is particularly useful for observation of deep tissues like bones. Here we
      introduce our data about osteoblast live cell imaging in vivo and in vitro
      including intravital imaging and summarize the latest reports about it.

PMID- 29371488
TI  - [Intravital bone imaging ~Osteocyte.]
AB  - Osteocytes are the most abundant cellular component of bone and have been
      considered dormant until recent evidence has demonstrated their critical roles in
      bone homeostasis and endocrine regulation. Until now the location of osteocytes
      within mineralized bone has restricted experimental access, especially in vivo.
      Here, intravital bone imaging by two-photon excitation microscopy allowed us to
      directly visualize the osteocytic lacuno-canalicular system. We demonstrated that
      sciatic neurectomy causes significant acidification around osteocytic lacunae and
      enlargement of lacuno-canalicular areas. These results show that two-photon
      intravital microscopy is useful for analysis of osteocytes in vivo.

PMID- 29371489
TI  - [Dynamic analysis of hematopoietic stem cells in the bone marrow by intravital
      imaging.]
AB  - Hematopoietic stem cells(HSCs)in the bone marrow(BM)are maintained in distinct
      microenvironments called niches. Technological advances in in vivo imaging have
      enabled dynamic analyses of BM cells. This in vivo imaging can be a key tool to
      elucidate the mechanisms underlying HSC maintenance in the BM through analysis of
      HSC motility and evaluation of the relationship between HSCs and their niche
      factors over time. Furthermore, application of this imaging technology to
      leukemia research can lead to new discoveries in leukemic stem cell maintenance
      and the development of novel antileukemic drugs. In this review, we summarize
      recent advances in dynamic analyses of HSCs and leukemic cells in the BM by
      intravital imaging.

PMID- 29371490
TI  - [The effects of anti-bone-resorptive drugs analyzed by intravital bone imaging.]
AB  - In clinical, various kinds of anti-bone-resorptive drugs have been used for the
      treatment of bone disorders such as osteoporosis. However, it remains elusive how
      they affect the osteoclast dynamics in living bone tissues. We recently succeeded
      in visualizing cellular dynamics of bone-resorbing osteoclasts and their
      precursors with intravital bone imaging techniques. We found that active vitamin
      D analogs could regulate the migratory behavior of circulating osteoclast
      precursors, whereas bisphosphonates could affect mature osteoclasts and inhibit
      bone resorption within a short period. Here we show the latest data of in vivo
      effects of anti-bone resorptive drugs currently developed in the world.

PMID- 29371491
TI  - [Analysis of the bone anabolic agent by intravital imaging technique.]
AB  - Teriparatide, recombinant human PTH(1-34), is the only anabolic agent widely used
      for osteoporosis. This drug is thought to promote bone formation by modulating
      bone remodeling system, although the detailed mechanism remains unclear.
      Recently, we developed a novel intravital imaging technique to visualize mature
      osteoclasts and mature osteoblasts simultaneously. By means of this system, we
      revealed the effect of teriparatide on three-dimensional distribution and cell-to
      cell interactions between these cells. Advances in these imaging studies may lead
      to further understanding of the intercellular network in bone metabolism.

PMID- 29371492
TI  - [Exosomal biomarkers for kidney disease.]
AB  - Development of minimally invasive biomarkers is necessary for early detection,
      prognosis prediction, severity assessment and treatment monitoring in different
      kidney diseases. Recently, many studies have been conducted worldwide on marker
      proteins and micro RNA(miRNA)contained in urinary extracellular
      vesicles(EVs)including exosomes. This article reviews urinary EV-contained
      biomarkers, including proximal tubular endocytic receptor megalin, for kidney
      diseases such as diabetic nephropathy.

PMID- 29371493
TI  - Risk-based Management of Non-muscle Invasive Bladder Cancer: Experience from
      Tribhuvan University Teaching Hospital.
AB  - Background Most of the recent evidences suggest for risk-based management of non
      muscle invasive bladder cancer (NMIBC) to reduce the risk of recurrence and
      progression. Objective This study was conducted to assess the recurrence and
      progression of non muscle invasive bladder cancer in Nepalese patients using
      European Organization for Research and Treatment of Cancer (EORTC) risk tables
      and to assess the effectiveness of intravesical therapy to reduce the risk of
      recurrence. Method A prospective observational single centre study was conducted
      at Tribhuvan University Teaching Hospital from January 2010- December 2012. Forty
      six patients with non muscle invasive bladder cancer who underwent transurethral
      resection of bladder tumor and completed two years follow up were included.
      According to the European Organization for Research and Treatment of Cancer
      (EORTC) risk table, the patients were divided into low, intermediate and high
      risk groups. The patients received postoperative adjuvant therapy and
      surveillance as per the European Association of Urology guidelines. Result Among
      the 46 patients, the overall two year recurrence and progression rate was 8 (17%)
      and 1 (2%) respectively. Out of seven patients in low risk category, none of them
      developed recurrence or progression of disease. Out of 15 patients in
      intermediate risk category the one year and two year recurrence rate was 13% and
      20% respectively. Out of 24 patients in high risk category the one and two year
      recurrence rate was 17% and 21% respectively. The risk reduction by use of
      intravesical Bacillus Calmette Guerin (BCG) for recurrence in high risk category
      was 58% and 60% in first and second year respectively. In our study, the overall
      and individual risk group, the one and two year recurrence rate was lower than
      that predicted by European Organization for Research and Treatment of Cancer risk
      table. Conclusion Risk-based management of non muscle invasive bladder cancer by
      using the European Organization for Research and Treatment of Cancer risk table
      is a useful method of management, though its prediction rates are lower in
      Nepalese population.

PMID- 29371495
TI  - Host Soluble Mediators: Defying the Immunological Inertness of Aspergillus
      fumigatus Conidia.
AB  - Aspergillus fumigatus produce airborne spores (conidia), which are inhaled in
      abundant quantity. In an immunocompromised population, the host immune system
      fails to clear the inhaled conidia, which then germinate and invade, leading to
      pulmonary aspergillosis. In an immunocompetent population, the inhaled conidia
      are efficiently cleared by the host immune system. Soluble mediators of the
      innate immunity, that involve the complement system, acute-phase proteins,
      antimicrobial peptides and cytokines, are often considered to play a
      complementary role in the defense of the fungal pathogen. In fact, the soluble
      mediators are essential in achieving an efficient clearance of the dormant
      conidia, which is the morphotype of the fungus upon inhalation by the host.
      Importantly, harnessing the host soluble mediators challenges the immunological
      inertness of the dormant conidia due to the presence of the rodlet and melanin
      layers. In the review, we summarized the major soluble mediators in the lung that
      are involved in the recognition of the dormant conidia. This knowledge is
      essential in the complete understanding of the immune defense against A.
      fumigatus.

PMID- 29371494
TI  - The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall
      Stress in Yeast.
AB  - Fungi are surrounded by an essential structure, the cell wall, which not only
      confers cell shape but also protects cells from environmental stress. As a
      consequence, yeast cells growing under cell wall damage conditions elicit rescue
      mechanisms to provide maintenance of cellular integrity and fungal survival.
      Through transcriptional reprogramming, yeast modulate the expression of genes
      important for cell wall biogenesis and remodeling, metabolism and energy
      generation, morphogenesis, signal transduction and stress. The yeast cell wall
      integrity (CWI) pathway, which is very well conserved in other fungi, is the key
      pathway for the regulation of this adaptive response. In this review, we
      summarize the current knowledge of the yeast transcriptional program elicited to
      counterbalance cell wall stress situations, the role of the CWI pathway in the
      regulation of this program and the importance of the transcriptional input
      received by other pathways. Modulation of this adaptive response through the CWI
      pathway by positive and negative transcriptional feedbacks is also discussed.
      Since all these regulatory mechanisms are well conserved in pathogenic fungi,
      improving our knowledge about them will have an impact in the developing of new
      antifungal therapies.

PMID- 29371496
TI  - Role of Hydrophobins in Aspergillus fumigatus.
AB  - Resistance of Aspergillus fumigatus conidia to desiccation and their capacity to
      reach the alveoli are partly due to the presence of a hydrophobic layer composed
      of a protein from the hydrophobin family, called RodA, which covers the conidial
      surface. In A. fumigatus there are seven hydrophobins (RodA-RodG) belonging to
      class I and III. Most of them have never been studied. We constructed single and
      multiple hydrophobin-deletion mutants until the generation of a hydrophobin-free
      mutant. The phenotype, immunogenicity, and virulence of the mutants were studied.
      RODA is the most expressed hydrophobin in sporulating cultures, whereas RODB is
      upregulated in biofilm conditions and in vivo Only RodA, however, is responsible
      for rodlet formation, sporulation, conidial hydrophobicity, resistance to
      physical insult or anionic dyes, and immunological inertia of the conidia. None
      of the hydrophobin plays a role in biofilm formation or its hydrophobicity. RodA
      is the only needed hydrophobin in A. fumigatus, conditioning the structure,
      permeability, hydrophobicity, and immune-inertia of the cell wall surface in
      conidia. Moreover, the defect of rodlets on the conidial cell wall surface
      impacts on the drug sensitivity of the fungus.

PMID- 29371497
TI  - Neuro-Immune Mechanisms of Anti-Cryptococcal Protection.
AB  - Cryptococcal meningitis (CM) is a life-threatening fungal disease affecting both
      immunosuppressed and immunocompetent people. The main causative agent of CM is
      Cryptococcus neoformans, a basidiomycete fungus prevalent in the environment. Our
      understanding of the immune mechanisms controlling C. neoformans growth within
      the central nervous system (CNS) is poor. However, there have been several recent
      advances in the field of neuroimmunology regarding how cells resident within the
      CNS, such as microglia and neurons, can participate in immune surveillance and
      control of infection. In this mini-review, the cells of the CNS are discussed
      with reference to what is currently known about how they control C. neoformans
      infection.

PMID- 29371498
TI  - Recent Insights into the Paradoxical Effect of Echinocandins.
AB  - Echinocandin antifungals represent one of the most important drug classes for the
      treatment of invasive fungal infections. The mode of action of the echinocandins
      relies on inhibition of the beta-1,3-glucan synthase, an enzyme essentially
      required for the synthesis of the major fungal cell wall carbohydrate beta-1,3
      glucan. Depending on the species, echinocandins may exert fungicidal or
      fungistatic activity. Apparently independent of this differential activity, a
      surprising in vitro phenomenon called the "paradoxical effect" can be observed.
      The paradoxical effect is characterized by the ability of certain fungal isolates
      to reconstitute growth in the presence of higher echinocandin concentrations,
      while being fully susceptible at lower concentrations. The nature of the
      paradoxical effect is not fully understood and has been the focus of multiple
      studies in the last two decades. Here we concisely review the current literature
      and propose an updated model for the paradoxical effect, taking into account
      recent advances in the field.

PMID- 29371500
TI  - Special Issue: Host-Fungus Interactions.
AB  - The clinical presentation of fungal disease is strongly determined by the
      underlying immune defect present [...].

PMID- 29371499
TI  - Diversity of Cell Wall Related Proteins in Human Pathogenic Fungi.
AB  - The cell wall is one of the major keys to fungal identity. Fungi use their cell
      wall to sense the environment, and localize nutrients and competing
      microorganism. Pathogenic species additionally modify their cell walls to hide
      from a host's immune system. With the growing number of fungal infections and
      alarming shortage of available drugs, we are in need of new approaches to fight
      pathogens. The cell wall seems to be a natural target, since animal host cells
      are devoid of it. The current knowledge about fungal cell wall components is
      often limited, and there is huge diversity both in structure and composition
      between species. In order to compare the distribution of diverse proteins
      involved in cell wall biosynthesis and maintenance, we performed sequence
      homology searches against 24 fungal proteomes from distinct taxonomic groups, all
      reported as human pathogens. This approach led to identification of 4014 cell
      wall proteins (CWPs), and enabled us to speculate about cell wall composition in
      recently sequenced pathogenic fungi with limited experimental information. We
      found large expansions of several CWP families, in particular taxa, and a number
      of new CWPs possibly involved in evading host immune recognition. Here, we
      present a comprehensive evolutionary history of fungal CWP families in the
      context of the fungal tree of life.

PMID- 29371501
TI  - Anti-Aspergillus Activities of the Respiratory Epithelium in Health and Disease.
AB  - Respiratory epithelia fulfil multiple roles beyond that of gaseous exchange, also
      acting as primary custodians of lung sterility and inflammatory homeostasis.
      Inhaled fungal spores pose a continual antigenic, and potentially pathogenic,
      challenge to lung integrity against which the human respiratory mucosa has
      developed various tolerance and defence strategies. However, respiratory disease
      and immune dysfunction frequently render the human lung susceptible to fungal
      diseases, the most common of which are the aspergilloses, a group of syndromes
      caused by inhaled spores of Aspergillus fumigatus. Inhaled Aspergillus spores
      enter into a multiplicity of interactions with respiratory epithelia, the
      mechanistic bases of which are only just becoming recognized as important drivers
      of disease, as well as possible therapeutic targets. In this mini-review we
      examine current understanding of Aspergillus-epithelial interactions and, based
      upon the very latest developments in the field, we explore two apparently
      opposing schools of thought which view epithelial uptake of Aspergillus spores as
      either a curative or disease-exacerbating event.

PMID- 29371503
TI  - Candida albicans Hyphae: From Growth Initiation to Invasion.
AB  - Candida albicans is a commensal resident of the human gastrointestinal and
      genital tracts. Under conditions such as dysbiosis, host immune perturbances, or
      the presence of catheters/implanted medical devices, the fungus may cause
      debilitating mucosal or fatal systemic infections. The ability of C. albicans to
      grow as long filamentous hyphae is critical for its pathogenic potential as it
      allows the fungus to invade the underlying substratum. In this brief review, I
      will outline the current understanding regarding the mechanistic regulation of
      hyphal growth and invasion in C. albicans.

PMID- 29371502
TI  - Patient Susceptibility to Candidiasis-A Potential for Adjunctive Immunotherapy.
AB  - Candida spp. are colonizing fungi of human skin and mucosae of the
      gastrointestinal and genitourinary tract, present in 30-50% of healthy
      individuals in a population at any given moment. The host defense mechanisms
      prevent this commensal fungus from invading and causing disease. Loss of skin or
      mucosal barrier function, microbiome imbalances, or defects of immune defense
      mechanisms can lead to an increased susceptibility to severe mucocutaneous or
      invasive candidiasis. A comprehensive understanding of the immune defense against
      Candida is essential for developing adjunctive immunotherapy. The important role
      of underlying genetic susceptibility to Candida infections has become apparent
      over the years. In most patients, the cause of increased susceptibility to fungal
      infections is complex, based on a combination of immune regulation gene
      polymorphisms together with other non-genetic predisposing factors.
      Identification of patients with an underlying genetic predisposition could help
      determine which patients could benefit from prophylactic antifungal treatment or
      adjunctive immunotherapy. This review will provide an overview of patient
      susceptibility to mucocutaneous and invasive candidiasis and the potential for
      adjunctive immunotherapy.

PMID- 29371506
TI  - Candidate Genes for Aggressiveness in a Natural Fusarium culmorum Population
      Greatly Differ between Wheat and Rye Head Blight.
AB  - Fusarium culmorum is one of the species causing Fusarium head blight (FHB) in
      cereals in Europe. We aimed to investigate the association between the nucleotide
      diversity of ten F. culmorum candidate genes and field ratings of aggressiveness
      in winter rye. A total of 100 F. culmorum isolates collected from natural
      infections were phenotyped for FHB at two locations and two years. Variance
      components for aggressiveness showed significant isolate and isolate-by
      environment variance, as expected for quantitative host-pathogen interactions.
      Further analysis of the isolate-by-environment interaction revealed the dominant
      role of the isolate-by-year over isolate-by-location interaction. One single
      nucleotide polymorphism (SNP) in the cutinase (CUT) gene was found to be
      significantly (p < 0.001) associated with aggressiveness and explained 16.05% of
      the genotypic variance of this trait in rye. The SNP was located 60 base pairs
      before the start codon, which suggests a role in transcriptional regulation.
      Compared to a previous study in winter wheat with the same nucleotide sequences,
      a larger variation of pathogen aggressiveness on rye was found and a different
      candidate gene was associated with pathogen aggressiveness. This is the first
      report on the association of field aggressiveness and a host-specific candidate
      gene codifying for a protein that belongs to the secretome in F. culmorum.

PMID- 29371507
TI  - Burden of Serious Fungal Infections in Jordan.
AB  - OBJECTIVE: To estimate the burden of fungal infections in Jordan for the first
      time. MATERIAL AND METHODS: Population data was from UN 2011 statistics and TB
      cases from WHO in 2012. Fewer than 100 patients with HIV were recorded in Jordan
      in 2013. Approximately 100 renal transplants and eight liver transplants are
      performed annually. There were 12,233 major surgical procedures in Jordan in
      2013, of which 5.3% were major abdominal surgeries; candidemia was estimated in
      5% of the population based on other countries, with 33% occurring in the ICU.
      Candida peritonitis/intra-abdominal candidiasis was estimated to affect 50% of
      the number of ICU candidemia cases. No adult asthma rates have been recorded for
      Jordan, so the rate from the Holy Land (8.54% clinical asthma) from To et al. has
      been used. There are an estimated 49,607 chronic obstructive pulmonary disease
      (COPD) patients in Jordan, with 64% symptomatic, 25% Gold stage 3% or 4%, and 7%
      (3472) are assumed to be admitted to hospital each year. No cystic fibrosis cases
      have been recorded. Literature searches on fungal infections revealed few data
      and no prevalence data on fungal keratitis or tinea capitis, even though tinea
      capitis comprised 34% of patients with dermatophytoses in Jordan. RESULTS: Jordan
      has 6.3 million inhabitants (65% adults, 6% are >60 years old). The current
      burden of serious fungal infections in Jordan was estimated to affect ~119,000
      patients (1.9%), not including any cutaneous fungal infections. Candidemia was
      estimated at 316 cases and invasive aspergillosis in leukemia, transplant, and
      COPD patients at 84 cases. Chronic pulmonary aspergillosis prevalence was
      estimated to affect 36 post-TB patients, and 175 in total. Allergic
      bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization
      (SAFS) prevalence in adults with asthma were estimated at 8900 and 11,748
      patients. Recurrent vulvovaginal candidiasis was estimated to affect 97,804
      patients, using a 6% rate among women 15-50 years of age. CONCLUSION: Based on
      local data and literature estimates of the frequency of mycoses in susceptible
      populations, at least 1.9% of Jordanians have some form of serious fungal
      disease.

PMID- 29371505
TI  - Gaining Insights from Candida Biofilm Heterogeneity: One Size Does Not Fit All.
AB  - Despite their clinical significance and substantial human health burden, fungal
      infections remain relatively under-appreciated. The widespread overuse of
      antibiotics and the increasing requirement for indwelling medical devices
      provides an opportunistic potential for the overgrowth and colonization of
      pathogenic Candida species on both biological and inert substrates. Indeed, it is
      now widely recognized that biofilms are a highly important part of their
      virulence repertoire. Candida albicans is regarded as the primary fungal biofilm
      forming species, yet there is also increasing interest and growing body of
      evidence for non-Candida albicans species (NCAS) biofilms, and interkingdom
      biofilm interactions. C. albicans biofilms are heterogeneous structures by
      definition, existing as three-dimensional populations of yeast, pseudo-hyphae,
      and hyphae, embedded within a self-produced extracellular matrix. Classical
      molecular approaches, driven by extensive studies of laboratory strains and
      mutants, have enhanced our knowledge and understanding of how these complex
      communities develop, thrive, and cause host-mediated damage. Yet our clinical
      observations tell a different story, with differential patient responses
      potentially due to inherent biological heterogeneity from specific clinical
      isolates associated with their infections. This review explores some of the
      recent advances made in an attempt to explore the importance of working with
      clinical isolates, and what this has taught us.

PMID- 29371508
TI  - Analysis of Transposable Elements in Coccidioides Species.
AB  - Coccidioides immitis and C. posadasii are primary pathogenic fungi that cause
      disease in immunologically-normal animals and people. The organism is found
      exclusively in arid regions of the Southwestern United States, Mexico, and South
      America, but not in other parts of the world. This study is a detailed analysis
      of the transposable elements (TE) in Coccidioides spp. As is common in most
      fungi, Class I and Class II transposons were identified and the LTR Gypsy
      superfamily is the most common. The minority of Coccidioides Gypsy transposons
      contained regions highly homologous to polyprotein domains. Phylogenetic analysis
      of the integrase and reverse transcriptase sequences revealed that many, but not
      all, of the Gypsy reverse transcriptase and integrase domains clustered by
      species suggesting extensive transposition after speciation of the two
      Coccidiodies spp. The TEs were clustered and the distribution is enriched for the
      ends on contigs. Analysis of gene expression data from C. immitis found that
      protein-coding genes within 1 kB of hAT or Gypsy TEs were poorly expressed. The
      expression of C. posadasii genes within 1 kB of Gypsy TEs was also significantly
      lower compared to all genes but the difference in expression was smaller than C.
      immitis. C. posadasii orthologs of C. immitis Gyspsy-associated genes were also
      likely to be TE-associated. In both C. immitis and C. posadasii the TEs were
      preferentially associated with genes annotated with protein kinase gene ontology
      terms. These observations suggest that TE may play a role in influencing gene
      expression in Coccidioides spp. Our hope is that these bioinformatic studies of
      the potential TE influence on expression and evolution of Coccidioides will
      prompt the development of testable hypotheses to better understand the role of
      TEs in the biology and gene regulation of Coccidioides spp.

PMID- 29371509
TI  - Biofilm Formation and Resistance to Fungicides in Clinically Relevant Members of
      the Fungal Genus Fusarium.
AB  - Clinically relevant members of the fungal genus, Fusarium, exhibit an
      extraordinary genetic diversity and cause a wide spectrum of infections in both
      healthy individuals and immunocompromised patients. Generally, Fusarium species
      are intrinsically resistant to all systemic antifungals. We investigated whether
      the presence or absence of the ability to produce biofilms across and within
      Fusarium species complexes is linked to higher resistance against antifungals. A
      collection of 41 Fusarium strains, obtained from 38 patients with superficial and
      systemic infections, and three infected crops, were tested, including 25 species
      within the Fusarium fujikuroi species complex, 14 from the Fusarium solani
      species complex (FSSC), one Fusarium dimerum species complex, and one Fusarium
      oxysporum species complex isolate. Of all isolates tested, only seven strains
      from two species of FSSC, five F. petroliphilum and two F. keratoplasticum
      strains, recovered from blood, nail scrapings, and nasal biopsy samples, could
      produce biofilms under the tested conditions. In the liquid culture tested,
      sessile biofilm-forming Fusarium strains exhibited elevated minimum inhibitory
      concentrations (MICs) for amphotericin B, voriconazole, and posaconazole,
      compared to their planktonic counterparts, indicating that the ability to form
      biofilm may significantly increase resistance. Collectively, this suggests that
      once a surface adherent biofilm has been established, therapies designed to kill
      planktonic cells of Fusarium are ineffective.

PMID- 29371511
TI  - N-acetylglucosamine-1-Phosphate Transferase Suppresses Lysosomal Hydrolases in
      Dysfunctional Osteoclasts: A Potential Mechanism for Vascular Calcification.
AB  - In addition to increased differentiation of vascular smooth muscle cells into
      osteoblast-like phenotypes, the limited accumulation of osteoclasts in
      atherosclerotic plaques or their dysfunction may participate in potential
      mechanisms for vascular calcification. N-acetylglucosamine-1-phosphate
      transferase containing alpha and beta subunits (GNPTAB) is a transmembrane enzyme
      complex that mediates the vesicular transport of lysosomal hydrolases. GNPTAB may
      also regulate the biogenesis of lysosomal hydrolases from bone-marrow derived
      osteoclasts. In this study, the areas surrounding calcification in human
      atherosclerotic plaques contained high levels of GNPTAB and low levels of
      lysosomal hydrolases such as cathepsin K (CTSK) and tartrate-resistant acid
      phosphatase (TRAP), as demonstrated by immunohistochemistry and laser-capture
      microdissection-assisted mRNA expression analysis. We therefore hypothesized that
      GNPTAB secretion may suppress the release of CTSK and TRAP by vascular osteoclast
      like cells, thus causing their dysfunction and reducing the resorption of
      calcification. We used human primary macrophages derived from peripheral blood
      mononuclear cells, an established osteoclast differentiation model. GNPTAB siRNA
      silencing accelerated the formation of functional osteoclasts as detected by
      increased secretion of CTSK and TRAP and increased their bone resorption activity
      as gauged by resorption pits assay. We concluded that high levels of GNPTAB
      inhibit secretion of lysosomal hydrolases in dysfunctional osteoclasts, thereby
      affecting their resorption potential in cardiovascular calcification.

PMID- 29371512
TI  - Glucose Serum Concentrations and Cardiovascular Disease in Patients on the End
      Stage of Renal Disease without Diabetes Mellitus.
AB  - Background/Aim: It is still controversial whether tighter glycemic control is
      associated with better clinical outcomes in patients with kidney failure. We
      examined the association between glucose serum concentrations and cardiovascular
      disease in patients on the end stage of renal disease without diabetes mellitus.
      Methods: We studied 76 patients on on-line hemodiafiltration. Cardiovascular
      disease was defined by the existence of coronary disease (CD). Arterial stiffness
      was measured as carotid-femoral pulse wave velocity (c-fPWV) and carotid
      augmentation index (AIx). The concentrations of beta2-microglobulin (beta2M) and
      insulin were measured by radioimmunoassays and insulin resistance by HOMA-IR. We
      built a logistic-regression analysis to examine the role of glucose on
      cardiovascular disease after adjustment for the traditional and specific risk
      factors for dialysis patients. Results: Serum glucose was positively correlated
      with beta2M, insulin and HOMA-IR (r = 0.361, p = 0.002, r = 0.581, p = 0.001 and
      r = 0.753, p = 0.001 respectively). Logistic-regression analysis did not show
      significant impact of glucose concentrations on cardiovascular disease after
      adjustment for traditional and specific risk factors. Conclusions: The
      association between elevated glucose serum concentrations and represented by
      coronary syndrome cardiovascular disease in patients on the end stage of renal
      disease without diabetes mellitus was not found significant.

PMID- 29371513
TI  - Rationale for the Cytogenomics of Cardiovascular Malformations Consortium: A
      Phenotype Intensive Registry Based Approach.
AB  - Cardiovascular malformations (CVMs) are the most common birth defect, occurring
      in 1%-5% of all live births. Although the genetic contribution to CVMs is well
      recognized, the genetic causes of human CVMs are identified infrequently. In
      addition, a failure of systematic deep phenotyping of CVMs, resulting from the
      complexity and heterogeneity of malformations, has obscured genotype-phenotype
      correlations and contributed to a lack of understanding of disease mechanisms. To
      address these knowledge gaps, we have developed the Cytogenomics of
      Cardiovascular Malformations (CCVM) Consortium, a multi-site alliance of
      geneticists and cardiologists, contributing to a database registry of
      submicroscopic genetic copy number variants (CNVs) based on clinical chromosome
      microarray testing in individuals with CVMs using detailed classification
      schemes. Cardiac classification is performed using a modification to the National
      Birth Defects Prevention Study approach, and non-cardiac diagnoses are captured
      through ICD-9 and ICD-10 codes. By combining a comprehensive approach to
      clinically relevant genetic analyses with precise phenotyping, the Consortium
      goal is to identify novel genomic regions that cause or increase susceptibility
      to CVMs and to correlate the findings with clinical phenotype. This registry will
      provide critical insights into genetic architecture, facilitate genotype
      phenotype correlations, and provide a valuable resource for the medical
      community.

PMID- 29371515
TI  - Neutron Scattering at the Intersection of Heart Health Science and Biophysics.
AB  - There is an urgent quest for improved heart health. Here, we review how neutron
      radiation can provide insight into the molecular basis of heart health. Lower
      cholesterol, a daily intake of aspirin and supplemental vitamin E are argued to
      all improve heart health. However, the mechanisms behind these common regimens,
      and others, are not entirely understood. It is not clear why a daily intake of
      aspirin can help some people with heart disease, and the benefits of vitamin E in
      the treatment of reperfusion injury have been heavily debated. The molecular
      impact of cholesterol in the body is still a hot topic. Neutron scattering
      experiments present a unique opportunity for biophysicists attempting to address
      these problems. We review some recently published studies that are advancing our
      understanding of how cholesterol, vitamin E and aspirin work at the molecular
      level, by studying the impact of these molecules on the cell membrane. These
      insights engage the broader health science community with new ways of thinking
      about these molecules.

PMID- 29371514
TI  - Advanced Electrocardiography Identifies Left Ventricular Systolic Dysfunction in
      Non-Ischemic Cardiomyopathy and Tracks Serial Change over Time.
AB  - : Electrocardiogram (ECG)-based detection of left ventricular systolic
      dysfunction (LVSD) has poor specificity and positive predictive value, even when
      including major ECG abnormalities, such as left bundle branch block (LBBB) within
      the criteria for diagnosis. Although machine-read ECG algorithms do not provide
      information on LVSD, advanced ECG (A-ECG), using multiparameter scores, has
      superior diagnostic utility to strictly conventional ECG for identifying various
      cardiac pathologies, including LVSD. METHODS: We evaluated the diagnostic utility
      of A-ECG in a case-control study of 40 patients with LVSD (LV ejection fraction <
      50% by echocardiography), due to non-ischemic cardiomyopathy (NICM), and 39 other
      patients without LVSD. Diagnostic sensitivity and specificity for LVSD were
      determined after applying a previously validated probabilistic A-ECG score for
      LVSD to stored standard (10 s) clinical 12L ECGs. In 25 of the NICM patients who
      had serial ECGs and echocardiograms, changes in the A-ECG score versus in
      echocardiographic LV ejection fraction were also studied to determine the level
      of agreement between the two tests. RESULTS: Analyses by A-ECG had a sensitivity
      of 95% for LVSD (93% if excluding N = 11 patients with LBBB) and specificity of
      95%. In the 29 NICM patients without LBBB who had serial ECGs, sensitivity
      improved to 97% when all ECGs were considered. By comparison, human readers in a
      busy clinical environment had a sensitivity of 90% and specificity of 63%. A-ECG
      score trajectories demonstrated improvement, deterioration or no change in LVSD,
      which agreed with echocardiography, in 76% of cases (n = 25). CONCLUSION: A-ECG
      scoring detects LVSD due to NICM with high sensitivity and specificity. Serial A
      ECG score trajectories also represent a method for inexpensively demonstrating
      changes in LVSD. A-ECG scoring may be of particular value in areas where
      echocardiography is unavailable, or as a gatekeeper for echocardiography.

PMID- 29371516
TI  - Imaging of Mitral Valve Prolapse: What Can We Learn from Imaging about the
      Mechanism of the Disease?
AB  - Mitral valve prolapse (MVP) is the most common mitral valve disorder affecting 2%
      3% of the general population. Two histological forms for the disease exist:
      Myxomatous degeneration and fibroelastic disease. Pathological evidence suggests
      the disease is not confined solely to the valve tissue, and accumulation of
      proteoglycans and fibrotic tissue can be seen in the adjacent myocardium of MVP
      patients. MVP is diagnosed by demonstrating valve tissue passing the annular line
      into the left atrium during systole. In this review we will discuss the
      advantages and limitations of various imaging modalities in their MVP diagnosis
      ability as well as the potential for demonstrating extra associated valvular
      pathologies.

PMID- 29371517
TI  - Investigation of the Matrix Metalloproteinase-2 Gene in Patients with Non
      Syndromic Mitral Valve Prolapse.
AB  - Non-syndromic mitral valve prolapse (MVP) is a common degenerative valvulopathy,
      predisposing to arrhythmia and sudden death. The etiology of MVP is suspected to
      be under genetic control, as supported by familial cases and its manifestation in
      genetic syndrome (e.g., Marfan syndrome). One candidate etiological mechanism is
      a perturbation of the extracellular matrix (ECM) remodeling of the valve. To test
      this hypothesis, we assessed the role of genetic variants in the matrix
      metalloproteinase 2 gene (MMP2) known to regulate the ECM turnover by direct
      degradation of proteins and for which transgenic mice develop MVP. Direct
      sequencing of exons of MMP2 in 47 unrelated patients and segregation analyses in
      families did not reveal any causative mutation. We studied eight common single
      nucleotide polymorphisms (TagSNPs), which summarize the genetic information at
      the MMP2 locus. The association study in two case controls sets (NCases = 1073
      and NControls = 1635) provided suggestive evidence for the association of
      rs1556888 located downstream MMP2 with the risk of MVP, especially in patients
      with the fibroelastic defiency form. Our study does not support the contribution
      of MMP2 rare variation in the etiology to MVP in humans, though further genetic
      and molecular investigation is required to confirm our current suggestive
      association of one common variant.

PMID- 29371518
TI  - Preliminary Evidence for Aortopathy and an X-Linked Parent-of-Origin Effect on
      Aortic Valve Malformation in a Mouse Model of Turner Syndrome.
AB  - Turner syndrome (TS), most frequently caused by X-monosomy (45,X), is
      characterized in part by cardiovascular abnormalities, including aortopathy and
      bicuspid aortic valve (BAV). There is a need for animal models that recapitulate
      the cardiovascular manifestations of TS. Extracellular matrix (ECM) organization
      and morphometrics of the aortic valve and proximal aorta were examined in adult
      39,XO mice (where the parental origin of the single X was paternal (39,XPO) or
      maternal (39,XMO)) and 40,XX controls. Aortic valve morphology was normal
      (tricuspid) in all of the 39,XPO and 40,XX mice studied, but abnormal (bicuspid
      or quadricuspid) in 15% of 39,XMO mice. Smooth muscle cell orientation in the
      ascending aorta was abnormal in all 39,XPO and 39,XMO mice examined, but smooth
      muscle actin was decreased in 39,XMO mice only. Aortic dilation was present with
      reduced penetrance in 39,XO mice. The 39,XO mouse demonstrates aortopathy and an
      X-linked parent-of-origin effect on aortic valve malformation, and the candidate
      gene FAM9B is polymorphically expressed in control and diseased human aortic
      valves. The 39,XO mouse model may be valuable for examining the mechanisms
      underlying the cardiovascular findings in TS, and suggest there are important
      genetic modifiers on the X chromosome that modulate risk for nonsyndromic BAV and
      aortopathy.

PMID- 29371519
TI  - Takotsubo Cardiomyopathy: A Long Term Follow-up Shows Benefit with Risk Factor
      Reduction.
AB  - Only sparse data was available on long-term of Takotusbo Cardiomyopathy (TC).
      Previous studies suggested prognosis is not necessarily benign. We report the
      long-term follow-up of 12 TC patients actively managed with risk factor
      reduction. Retrospective analysis of all patients diagnosed with TC at our
      hospital between 1998 and 2010. We identified 12 patients with TC among 1651
      cases of emergent left heart catheterization over 12 years. Mean follow-up time
      was 8.3 +/- 3.6 years. All were female, 87% had hypertension, 25% had history of
      Coronary Artery Disease (CAD), 67% had hyperlipidemia, 44% had some preceding
      emotional trauma, and 44% had some physical/physiological stress. Previous
      studies have shown that over 50% of TC patients experience future cardiac events,
      and 10% have a recurrence of TC. Patients were prescribed therapeutic lifestyle
      changes (TLC) and guideline directed medical therapy (GDMT) for aggressive risk
      factor reduction. TLC included diet, exercise, and cardiac rehabilitation. GDMT
      often included aspirin, beta-blockers, ACE-inhibitors, and statins. Follow-up
      echocardiograms showed recovery and maintenance of the ejection fraction. There
      was no cardiac mortality and no recurrences of TC. Aggressive risk factor
      reduction with TLC and GDMT may be effective in improving the long term outcomes
      of patients with TC.

PMID- 29371521
TI  - Biocontrol Properties of Basidiomycetes: An Overview.
AB  - In agriculture, there is an urgent need for alternate ecofriendly products to
      control plant diseases. These alternate products must possess preferable
      characteristics such as new modes of action, cost effectiveness,
      biodegradability, and target specificity. In the current scenario, studies on
      macrofungi have been an area of importance for scientists. Macrofungi grow
      prolifically and are found in many parts of the world. Basidiomycetes (mushrooms)
      flourish ubiquitously under warm and humid climates. Basidiomycetes are rich
      sources of natural antibiotics. The secondary metabolites produced by them
      possess antimicrobial, antitumor, and antioxidant properties. The present review
      discusses the potential role of Basidiomycetes as anti-phytofungal, anti
      phytobacterial, anti-phytoviral, mosquito larvicidal, and nematicidal agents.

PMID- 29371520
TI  - New Trends in Paracoccidioidomycosis Epidemiology.
AB  - Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America
      and more prevalent in South America. The disease is caused by the dimorphic
      fungus Paracoccidioides spp. whose major hosts are humans and armadillos. The
      fungus grows in soil and its infection is associated with exposure to the rural
      environment and to agricultural activities, with a higher risk in coffee and
      tobacco plantations. Population studies assessing the reactivity to
      Paracoccidioides spp. antigens by intradermal reaction or serological tests have
      detected previous subclinical infections in a significant proportion of healthy
      individuals living in various endemic countries. Paracoccidioidomycosis-disease
      is manifested by a small minority of infected individuals. The risk of developing
      the disease and its type of clinical form are related to the personal and life
      style characteristics of infected individuals, including genetic background, age,
      sex, ethnicity, smoking habit, alcohol drinking, and eventual cellular
      immunosuppression. Brazil, Colombia, Venezuela, Argentina, and Ecuador have
      endemic areas that had already been defined in the 20th century. The incidence of
      paracoccidioidomycosis can be altered by climate phenomena and mainly by human
      migration and occupation of poorly explored territories. In Brazil, the endemy
      tends to expand towards the North and Center-West around the Amazon Region.

PMID- 29371523
TI  - Entomopathogenicity and Biological Attributes of Himalayan Treasured Fungus
      Ophiocordyceps sinensis (Yarsagumba).
AB  - Members of the entomophagous fungi are considered very crucial in the fungal
      domain relative to their natural phenomenon and economic perspectives; however,
      inadequate knowledge of their mechanisms of interaction keeps them lagging behind
      in parallel studies of fungi associated with agro-ecology, forest pathology and
      medical biology. Ophiocordyceps sinensis (syn. Cordyceps sinensis), an intricate
      fungus-caterpillar complex after it parasitizes the larva of the moth, is a
      highly prized medicinal fungus known widely for ages due to its peculiar
      biochemical assets. Recent technological innovations have significantly
      contributed a great deal to profiling the variable clinical importance of this
      fungus and other related fungi with similar medicinal potential. However, a
      detailed mechanism behind fungal pathogenicity and fungal-insect interactions
      seems rather ambiguous and is poorly justified, demanding special attention. The
      goal of the present review is to divulge an update on the published data and
      provides promising insights on different biological events that have remained
      underemphasized in previous reviews on fungal biology with relation to life
      history trade-offs, host specialization and selection pressures. The infection of
      larvae by a fungus is not a unique event in Cordyceps; hence, other fungal
      species are also reviewed for effective comparison. Conceivably, the rationale
      and approaches behind the inheritance of pharmacological abilities acquired and
      stored within the insect framework at a time when they are completely hijacked
      and consumed by fungal parasites, and the molecular mechanisms involved therein,
      are clearly documented.

PMID- 29371524
TI  - Global Aspects of Triazole Resistance in Aspergillus fumigatus with Focus on
      Latin American Countries.
AB  - Azole resistance in Aspergillus has emerged as an escalating problem in health
      care, and it has been detected in patients exposed, or not, to these drugs. It is
      known that azole antifungals are widely applied not only in clinical treatments
      for fungal infections, but also as agricultural fungicides, resulting in a
      significant threat for human health. Although the number of cases of azole
      resistant aspergillosis is still limited, various resistance mechanisms are
      described from clinical and environmental isolates. These mechanisms consist
      mainly of alterations in the target of azole action (CYP51A gene)-specifically on
      TR34/L98H and TR46/Y121F/T289A, which are responsible for over 90% of resistance
      cases. This review summarizes the epidemiology, management, and extension of
      azole resistance in A. fumigatus worldwide and its potential impact in Latin
      American countries, emphasizing its relevance to clinical practice.

PMID- 29371525
TI  - Cutaneous Disseminated and Extracutaneous Sporotrichosis: Current Status of a
      Complex Disease.
AB  - Sporotrichosis is an implantation or inoculation mycosis caused by species of
      Sporothrix schenckii complex; its main manifestations are limited to skin;
      however, cutaneous-disseminated, disseminated (visceral) and extracutaneous
      variants of sporotrichosis can be associated with immunosuppression, including
      HIV-AIDS, chronic alcoholism or more virulent strains. The most common
      extracutaneous form of sporotrichosis includes pulmonary, osteoarticular and
      meningeal. The laboratory diagnosis requires observing yeast forms and isolating
      the fungus; the two main causative agents are Sporothrix schenckii (ss) and
      Sporothrix brasiliensis. Antibody levels and species recognition by Polimerase
      Chain Reaction using biological samples or cultures are also useful. The
      treatment of choice for most cases is amphotericin B and subsequent itraconazole
      for maintenance therapy.

PMID- 29371526
TI  - Comparative Efficacies of Antimicrobial Catheter Lock Solutions for Fungal
      Biofilm Eradication in an in Vitro Model of Catheter-Related Fungemia.
AB  - Fungal catheter-related bloodstream infections (CRBSIs)-primarily due to Candida
      species-account for over 12% of all CRBSIs, and have been progressively
      increasing in prevalence. They present significant health and economic burdens,
      and high mortality rates. Antimicrobial catheter lock solutions are an important
      prophylactic option for preventing fungal CRBSIs. In this study, we compared the
      effectiveness of two FDA-approved catheter lock solutions (heparin and saline)
      and three experimental antimicrobial catheter lock solutions-30% citrate,
      taurolidine-citrate-heparin (TCH), and nitroglycerin-citrate-ethanol (NiCE)-in an
      in vitro model of catheters colonized by fungi. The fungi tested were five
      different strains of Candida clinical isolates from cancer patients who
      contracted CRBSIs. Time-to-biofilm-eradication was assessed in the model with 15,
      30, and 60 min exposures to the lock solutions. Only the NiCE lock solution was
      able to fully eradicate all fungal biofilms within 60 min. Neither 30% citrate
      nor TCH was able to fully eradicate any of the Candida biofilms in this time
      frame. The NiCE lock solution was significantly superior to TCH in eradicating
      biofilms of five different Candida species (p = 0.002 for all).

PMID- 29371528
TI  - Combinatorial Biosynthesis of Novel Multi-Hydroxy Carotenoids in the Red Yeast
      Xanthophyllomyces dendrorhous.
AB  - The red yeast Xanthophyllomyces dendrorhous is an established platform for the
      synthesis of carotenoids. It was used for the generation of novel multi
      oxygenated carotenoid structures. This was achieved by a combinatorial approach
      starting with the selection of a beta-carotene accumulating mutant, stepwise
      pathway engineering by integration of three microbial genes into the genome and
      finally the chemical reduction of the resulting 4,4'-diketo-nostoxanthin
      (2,3,2',3'-tetrahydroxy-4,4'-diketo-beta-carotene) and 4-keto-nostoxanthin
      (2,3,2',3'-tetrahydroxy-4-monoketo-beta-carotene). Both keto carotenoids and the
      resulting 4,4'-dihydroxy-nostoxanthin (2,3,4,2',3',4'-hexahydroxy-beta-carotene)
      and 4-hydroxy-nostoxanthin (2,3,4,2'3'-pentahydroxy-beta-carotene) were separated
      by high-performance liquid chromatography (HPLC) and analyzed by mass
      spectrometry. Their molecular masses and fragmentation patterns allowed the
      unequivocal identification of all four carotenoids.

PMID- 29371527
TI  - Candida Species Biofilms' Antifungal Resistance.
AB  - Candida infections (candidiasis) are the most prevalent opportunistic fungal
      infection on humans and, as such, a major public health problem. In recent
      decades, candidiasis has been associated to Candida species other than Candida
      albicans. Moreover, biofilms have been considered the most prevalent growth form
      of Candida cells and a strong causative agent of the intensification of
      antifungal resistance. As yet, no specific resistance factor has been identified
      as the sole responsible for the increased recalcitrance to antifungal agents
      exhibited by biofilms. Instead, biofilm antifungal resistance is a complex
      multifactorial phenomenon, which still remains to be fully elucidated and
      understood. The different mechanisms, which may be responsible for the intrinsic
      resistance of Candida species biofilms, include the high density of cells within
      the biofilm, the growth and nutrient limitation, the effects of the biofilm
      matrix, the presence of persister cells, the antifungal resistance gene
      expression and the increase of sterols on the membrane of biofilm cells. Thus,
      this review intends to provide information on the recent advances about Candida
      species biofilm antifungal resistance and its implication on intensification of
      the candidiasis.

PMID- 29371529
TI  - The Crucial Role of Biofilms in Cryptococcus neoformans Survival within
      Macrophages and Colonization of the Central Nervous System.
AB  - Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing
      life threatening meningoencephalitis in patients with impaired immunity. This
      microbe primarily infects the host via inhalation but has the ability to
      disseminate to the central nervous system (CNS) either as a single cell or inside
      of macrophages. Upon traversing the blood brain barrier, C. neoformans has the
      capacity to form biofilm-like structures known as cryptococcomas. Hence, we will
      discuss the C. neoformans elements contributing to biofilm formation including
      the fungus' ability to survive in the acidic environment of a macrophage
      phagosome and inside of the CNS. The purpose of this mini-review is to instill
      fresh interest in understanding the importance of biofilms on fungal
      pathogenesis.

PMID- 29371531
TI  - Characterization of Blue Mold Penicillium Species Isolated from Stored Fruits
      Using Multiple Highly Conserved Loci.
AB  - Penicillium is a large genus of common molds with over 400 described species;
      however, identification of individual species is difficult, including for those
      species that cause postharvest rots. In this study, blue rot fungi from stored
      apples and pears were isolated from a variety of hosts, locations, and years.
      Based on morphological and cultural characteristics and partial amplification of
      the beta-tubulin locus, the isolates were provisionally identified as several
      different species of Penicillium. These isolates were investigated further using
      a suite of molecular DNA markers and compared to sequences of the ex-type for
      cognate species in GenBank, and were identified as P. expansum (3 isolates), P.
      solitum (3 isolates), P. carneum (1 isolate), and P. paneum (1 isolate). Three of
      the markers we used (ITS, internal transcribed spacer rDNA sequence; benA, beta
      tubulin; CaM, calmodulin) were suitable for distinguishing most of our isolates
      from one another at the species level. In contrast, we were unable to amplify
      RPB2 sequences from four of the isolates. Comparison of our sequences with
      cognate sequences in GenBank from isolates with the same species names did not
      always give coherent data, reinforcing earlier studies that have shown large
      intraspecific variability in many Penicillium species, as well as possible errors
      in some sequence data deposited in GenBank.

PMID- 29371532
TI  - Real-Time Approach to Flow Cell Imaging of Candida albicans Biofilm Development.
AB  - The ability of Candida albicans to form biofilms is a virulence factor that
      allows tissue attachment and subsequent infection of host tissues. Fungal
      biofilms have been particularly well studied, however the vast majority of these
      studies have been conducted under static conditions. Oral biofilms form in the
      presence of salivary flow, therefore we developed a novel flow system used for
      real-time imaging of fungal biofilm development. C. albicans wild-type (WT) cells
      readily attached to the substrate surface during the 2 h attachment phase, then
      formed heterogeneous biofilms after 18 h flow. Quantitative values for biomass,
      rates of attachment and detachment, and cell-cell adhesion events were obtained
      for C. albicans WT cells and for a hyperfilamentous mutant Deltahog1. Attachment
      rates of C. albicans WT cells were nearly 2-fold higher than C. albicans
      Deltahog1 cells, although Deltahog1 cells formed 4-fold higher biomass. The
      reduced normalized detachment rate was the primary factor responsible for the
      increased biomass of Deltahog1 biofilm, showing that cell detachment rates are an
      important predictor for ultimate biofilm mass under flow. Unlike static biofilms,
      C. albicans cells under constant laminar flow undergo continuous detachment and
      seeding that may be more representative of the development of in vivo biofilms.

PMID- 29371533
TI  - Microscopic Analysis of Pigments Extracted from Spalting Fungi.
AB  - Pigments that are currently available in the market usually come from synthetic
      sources, or, if natural, often need mordants to bind to the target substrate.
      Recent research on the fungal pigment extracts from Scytalidium cuboideum,
      Scytalidium ganodermophthorum, Chlorociboria aeruginosa, and Chlorociboria
      aeruginascens have been shown to successfully dye materials, like wood, bamboo,
      and textiles, however, there is no information about their binding mechanisms.
      Due to this, a microscopic study was performed to provide information to future
      manufacturers interested in these pigments. The results of this study show that
      S. ganodermophthorum and C. aeruginosa form an amorphous layer on substrates,
      while S. cuboideum forms crystal-like structures. The attachment and morphology
      indicate that there might be different chemical and physical interactions between
      the extracted pigments and the materials. This possibility can explain the high
      resistance of the pigments to UV light and color fastness that makes them
      competitive against synthetic pigments. These properties make these pigments a
      viable option for an industry that demands natural pigments with the properties
      of the synthetic ones.

PMID- 29371530
TI  - Candida glabrata Biofilms: How Far Have We Come?
AB  - Infections caused by Candida species have been increasing in the last decades and
      can result in local or systemic infections, with high morbidity and mortality.
      After Candida albicans, Candida glabrata is one of the most prevalent pathogenic
      fungi in humans. In addition to the high antifungal drugs resistance and
      inability to form hyphae or secret hydrolases, C. glabrata retain many virulence
      factors that contribute to its extreme aggressiveness and result in a low
      therapeutic response and serious recurrent candidiasis, particularly biofilm
      formation ability. For their extraordinary organization, especially regarding the
      complex structure of the matrix, biofilms are very resistant to antifungal
      treatments. Thus, new approaches to the treatment of C. glabrata's biofilms are
      emerging. In this article, the knowledge available on C. glabrata's resistance
      will be highlighted, with a special focus on biofilms, as well as new therapeutic
      alternatives to control them.

PMID- 29371534
TI  - Activity of Amphotericin B and Anidulafungin Combined with Rifampicin,
      Clarithromycin, Ethylenediaminetetraacetic Acid, N-Acetylcysteine, and Farnesol
      against Candida tropicalis Biofilms.
AB  - We evaluated the activity of (1) amphotericin-B (AMB), combined with rifampicin
      (RIF), clarithromycin (CLA), N-acetylcysteine (NAC), ethylenediaminetetraacetic
      acid (EDTA), and farnesol (FAR) (1000, 1000, 1000, 4000, and 30,000 mg/L, and 300
      uM, respectively), against Candida tropicalis biofilms formed on
      polytetrafluoroethylene (PTFE) and (2) anidulafungin (ANF) combined with the same
      compounds at 8, 10, 5, 40, and 30 mg/L, and 30 uM, respectively, against biofilms
      formed on titanium. Biofilm growth kinetics were performed in a CDC Biofilm
      Reactor (CBR). PTFE or titanium disks were removed from the CBR at 24, 48, 72,
      and 96 h to determine the Log10CFU/cm2. Killing kinetics were performed by adding
      the drugs to 24-h-mature biofilms (time 0). Disks were removed after 24, 48, and
      72 h of drug exposure to determine Log10CFU/cm2. Viable cells in biofilms were
      4.73 and 4.29 Log10CFU/cm2 on PTFE and titanium, respectively. Maximum Log10
      decreases in CFU/cm2 depend on the combination and were: 3.53 (AMB + EDTA), 2.65
      (AMB + RIF), 3.07 (AMB + NAC), 2.52 (AMB + CLA), 1.49 (AMB + FAR), 2.26 (ANF +
      EDTA), 2.45 (ANF + RIF), 2.47 (ANF + NAC), 1.52 (ANF + CLA), and 0.44 (ANF +
      FAR). In conclusion, EDTA, NAC, RIF, and CLA improve the activity of AMB and ANF
      against biofilms developed on both surfaces, which could be an effective strategy
      against C. tropicalis biofilm-related infections.

PMID- 29371535
TI  - Molecular Identification and Antifungal Susceptibility Patterns of Clinical
      Dermatophytes Following CLSI and EUCAST Guidelines.
AB  - Dermatophytes are associated with superficial infections in humans worldwide. The
      aim of the present study was to determine the species distribution and
      susceptibility patterns of clinical dermatophytes. Samples received for routine
      mycological processing from 124 suspected cases attending a dermatologic clinic
      in a tertiary care hospital were included in the study. On direct microscopy,
      74.1% (92/124) were positive and 53.2% (66/124) grew on culture. The isolates
      were comprised of Trichophytoninterdigitale (56%) followed by
      Trichophytontonsurans (25.7%), Trichophytonrubrum (7.5%), Trichophytonviolaceum
      (4.5%), Microsporumgypseum (4.5%), and Trichophytonverrucosum (1.5%).
      Conventional mycological identification was concordant with ITS sequencing except
      for T.mentagrophytes. High minimum inhibitory concentration (MIC) values
      (geometric mean, >1 ug/mL) were observed for T.tonsurans and T.rubrum to
      terbinafine and griseofulvin. This study highlights the shift in epidemiology
      from T.rubrum to T.interdigitale. It also raises a concern of high MICs of
      terbinafine and griseofulvin among our isolates. Surveillance of antifungal
      susceptibility patterns can provide clinicians with local MIC data that can
      further aid in guiding better management in relapse cases of dermatomycosis.

PMID- 29371536
TI  - Reduced Multidrug Susceptibility Profile Is a Common Feature of Opportunistic
      Fusarium Species: Fusarium Multi-Drug Resistant Pattern.
AB  - The resistance among various opportunistic Fusarium species to different
      antifungal agents has emerged as a cause of public health problems worldwide.
      Considering the significance of multi-drug resistant (MDR), this paper emphasizes
      the problems associated with MDR and the need to understand its clinical
      significance to combat microbial infections. The search platform PubMed/MEDLINE
      and a review of 32 cases revealed a common multidrug-resistant profile exists,
      and clinically relevant members of Fusarium are intrinsically resistant to most
      currently used antifungals. Dissemination occurs in patients with prolonged
      neutropenia, immune deficiency, and especially hematological malignancies.
      Amphotericin B displayed the lowest minimum inhibitory concentrarions (MICs)
      followed by voriconazole, and posaconazole. Itraconazole and fluconazole showed
      high MIC values, displaying in vitro resistance. Echinocandins showed the highest
      MIC values. Seven out of ten (70%) patients with neutropenia died, including
      those with fungemia that progressed to skin lesions. Clinical Fusarium isolates
      displayed a common MDR profile and high MIC values for the most available
      antifungal agents with species- and strain-specific differences in antifungal
      susceptibility. Species identification of Fusarium infections is important. While
      the use of natamycin resulted in a favorable outcome in keratitis, AmB and VRC
      are the most used agents for the treatment of fusariosis in clinical settings.

PMID- 29371537
TI  - Antifungal Susceptibility Testing of Fusarium: A Practical Approach.
AB  - In vitro susceptibility testing of Fusarium is becoming increasingly important
      because of frequency and diversity of infections and because resistance profiles
      are species-specific. Reference methods for antifungal susceptibility testing
      (AFST) are those of Clinical and Laboratory Standards Institute (CLSI) and
      European Committee on Antimicrobial Susceptibility (EUCAST), but breakpoints
      (BPs) have not yet been established. One of the problems is that phylogenetic
      distances between Fusarium species are much smaller than between species of,
      e.g., Candida. Epidemiological cutoff values (ECVs) for some Fusarium species
      have been determined in order to differentiate wild-type from non-wild-type
      isolates. In clinical routine, commercially available assays such as Etest,
      Sensititre or others provide essential agreement with reference methods. Our
      objective is to summarize antifungal susceptibility testing of Fusarium genus in
      the clinical laboratory: how to do it, when to do it, and how to interpret it.

PMID- 29371538
TI  - An Assessment of In Vitro Antifungal Activities of Efinaconazole and Itraconazole
      against Common Non-Dermatophyte Fungi Causing Onychomycosis.
AB  - Onychomycosis is a fungal nail infection which is relatively common and difficult
      to treat. Treatment modalities include nail avulsion, surgical debridement and
      combination therapy with oral and topical antifungal drugs. In spite of a host of
      available drugs, clinical cure rates remain discouraging. Drug toxicities,
      prolonged regimens, lack of patient compliance, and high keratin affinity of
      drugs are all contributive factors. Efinaconazole is a novel topical triazole
      antifungal agent that has shown excellent in vitro activity against both
      dermatophyte and non-dermatophyte fungi causing onychomycosis. This study
      presents the in vitro susceptibility profiles of 44 common non-dermatophyte fungi
      against efinaconazole and itraconazole, another azole drug used in the treatment
      of onychomycosis.

PMID- 29371539
TI  - Quantitative Assessment of Grapevine Wood Colonization by the Dieback Fungus
      Eutypa lata.
AB  - Eutypa lata is a fungal pathogen causing severe dieback in vineyards worldwide.
      This fungus colonizes vines through pruning wounds, eventually causing a brown
      sectorial necrosis in wood as well as stunted vegetative growth. Several years
      may pass between infection and the expression of external symptoms, hindering the
      rapid evaluation of both grapevine cultivars susceptibility and E. lata variation
      in aggressiveness. We aimed to develop a rapid quantitative method for the
      assessment of wood colonization after inoculation of cuttings in controlled
      conditions. We used several grape cultivars varying in susceptibility in the
      vineyard and fungal isolates with different levels of aggressiveness to monitor
      wood colonization during a maximum period of 2 months. Re-isolation allowed
      demonstration of the effects of both cultivars and fungal isolates on the rate of
      wood colonization. We also developed a real-time PCR method that was efficient in
      measuring fungal biomass, which was found to be correlated with isolate
      aggressiveness based on foliar symptom severity. The real-time PCR approach
      appears to be a useful technology to evaluate grapevine susceptibility to E.
      lata, and could be adapted to other pathogens associated with grapevine trunk
      diseases.

PMID- 29371541
TI  - Local-Level Genetic Diversity and Structure of Matsutake Mushroom (Tricholoma
      matsutake) Populations in Nagano Prefecture, Japan, Revealed by 15 Microsatellite
      Markers.
AB  - The annual yield of matsutake mushrooms (Tricholoma matsutake) has consistently
      decreased in Japan over the past few decades. We used 15 polymorphic and
      codominant simple sequence repeat (SSR) markers, developed using next-generation
      sequencing, to carry out genetic analyses of 10 populations in Nagano, Japan.
      Using the SSRs, we identified 223 genotypes, none of which was observed in more
      than one population. The mean expected heterozygosity and standardized allelic
      richness values were 0.67 and 4.05, respectively. Many alleles appeared in only
      one of the 10 populations; 34 of these private alleles were detected with a mean
      number per population of 3.4. The fixation index (FST) and standardized genetic
      differentiation (G'ST) values were 0.019 and 0.028, respectively. Analysis of
      molecular variance (AMOVA) showed that the contribution of among population,
      among genets within a population, and within genets variation to the total
      variation was 2.91%, 11.62%, and 85.47%, respectively, with genetic
      differentiation being detected for all sources. Twenty-eight of 45 pairwise FST
      values were significantly larger than zero, and no pattern of isolation by
      distance was detected among the 10 populations. Bayesian-based clustering did not
      show clear differences among populations. These results suggest that
      reestablishment of a colony would be best accomplished by transplantation within
      a field; if this is not possible, then transplantation from within several dozen
      kilometers will cause little damage to the original population genetic structure.

PMID- 29371542
TI  - Revisiting Species Distribution and Antifungal Susceptibility of Candida
      Bloodstream Isolates from Latin American Medical Centers.
AB  - The epidemiology of candidemia varies geographically, and there is still scarce
      data on the epidemiology of candidemia in Latin America (LA). After extensive
      revision of medical literature, we found reliable and robust information on the
      microbiological aspects of candidemia in patients from 11 out of 21 medical
      centers from LA countries and 1 out of 20 from Caribbean countries/territories.
      Based on 40 papers attending our search strategy, we noted that C. albicans
      remains the most common species causing candidemia in our region, followed by C.
      parapsilosis and C. tropicalis. In Argentina, Brazil, and Colombia, a trend
      towards an increase in frequency of C. glabrata candidemia was observed. Although
      resistance rates to fluconazole is under 3%, there was a slight increase in the
      resistance rates to C. albicans, C. parapsilosis and C. tropicalis isolates.
      Echinocandin resistance has been reported in a few surveys, but no single study
      confirmed the resistant phenotype reported by using molecular methods. We
      highlight the importance of conducting continuous surveillance studies to
      identify new trends in terms of species distribution of Candida and antifungal
      resistance related to episodes of candidemia in LA. This information is critical
      for helping clinicians to prevent and control Candida bloodstream infections in
      their medical centers.

PMID- 29371540
TI  - Fungal Biofilms and Polymicrobial Diseases.
AB  - Biofilm formation is an important virulence factor for pathogenic fungi. Both
      yeasts and filamentous fungi can adhere to biotic and abiotic surfaces,
      developing into highly organized communities that are resistant to antimicrobials
      and environmental conditions. In recent years, new genera of fungi have been
      correlated with biofilm formation. However, Candida biofilms remain the most
      widely studied from the morphological and molecular perspectives. Biofilms formed
      by yeast and filamentous fungi present differences, and studies of polymicrobial
      communities have become increasingly important. A key feature of resistance is
      the extracellular matrix, which covers and protects biofilm cells from the
      surrounding environment. Furthermore, to achieve cell-cell communication,
      microorganisms secrete quorum-sensing molecules that control their biological
      activities and behaviors and play a role in fungal resistance and pathogenicity.
      Several in vitro techniques have been developed to study fungal biofilms, from
      colorimetric methods to omics approaches that aim to identify new therapeutic
      strategies by developing new compounds to combat these microbial communities as
      well as new diagnostic tools to identify these complex formations in vivo. In
      this review, recent advances related to pathogenic fungal biofilms are addressed.

PMID- 29371544
TI  - Innate and Adaptive Immune Defects in Chronic Pulmonary Aspergillosis.
AB  - We evaluated the expression of biomarkers of innate and adaptive immune response
      in correlation with underlying conditions in 144 patients with chronic pulmonary
      aspergillosis (CPA). Patients with complete medical and radiological records,
      white cell counts, and a complete panel of CD3, CD4, CD8, CD19, and CD56
      lymphocyte subsets were included. Eighty-four (58%) patients had lymphopenia. Six
      (4%) patients had lymphopenia in all five CD variables. There were 62 (43%)
      patients with low CD56 and 62 (43%) patients with low CD19. Ten (7%) patients had
      isolated CD19 lymphopenia, 18 (13%) had isolated CD56 lymphopenia, and 15 (10%)
      had combined CD19 and CD56 lymphopenia only. Forty-eight (33%) patients had low
      CD3 and 46 (32%) had low CD8 counts. Twenty-five (17%) patients had low CD4, 15
      (10%) of whom had absolute CD4 counts <200/MUL. Multivariable logistic regression
      showed associations between: low CD19 and pulmonary sarcoidosis (Odds Ratio (OR),
      5.53; 95% Confidence Interval (CI), 1.43-21.33; p = 0.013), and emphysema (OR,
      4.58; 95% CI; 1.36-15.38; p = 0.014), low CD56 and no bronchiectasis (OR, 0.27;
      95% CI, 0.10-0.77; p = 0.014), low CD3 and both multicavitary CPA disease (OR,
      2.95; 95% CI, 1.30-6.72; p = 0.010) and pulmonary sarcoidosis (OR, 4.94; 95% CI,
      1.39-17.57; p = 0.014). Several subtle immune defects are found in CPA.

PMID- 29371543
TI  - NK Cells and Their Role in Invasive Mold Infection.
AB  - There is growing evidence that Natural Killer (NK) cells exhibit in vitro
      activity against both Aspergillus and non-Aspergillus molds. Cytotoxic molecules
      such as NK cell-derived perforin seem to play an important role in the antifungal
      activity. In addition, NK cells release a number of cytokines upon stimulation by
      fungi, which modulate both innate and adaptive host immune responses. Whereas the
      in vitro data of the antifungal activity of NK cells are supported by animal
      studies, clinical data are scarce to date.

PMID- 29371545
TI  - MIC Distributions and Evaluation of Fungicidal Activity for Amphotericin B,
      Itraconazole, Voriconazole, Posaconazole and Caspofungin and 20 Species of
      Pathogenic Filamentous Fungi Determined Using the CLSI Broth Microdilution
      Method.
AB  - For filamentous fungi (moulds), species-specific interpretive breakpoints and
      epidemiological cut-off values (ECVs) have only been proposed for a limited
      number of fungal species-antifungal agent combinations, with the result that
      clinical breakpoints are lacking for most emerging mould pathogens. In the
      current study, we have compiled minimum inhibitory concentration (MIC) data for
      4869 clinical mould isolates and present full MIC distributions for amphotericin
      B, itraconazole, voriconazole, posaconazole, and caspofungin with these isolates
      which comprise 20 species/genera. In addition, we present the results of an
      assessment of the fungicidal activity of these same five antifungal agents
      against a panel of 123 mould isolates comprising 16 of the same species.

PMID- 29371546
TI  - Monocyte Phenotype and IFN-gamma-Inducible Cytokine Responses Are Associated with
      Cryptococcal Immune Reconstitution Inflammatory Syndrome.
AB  - A third of adults with AIDS and cryptococcal meningitis (CM) develop immune
      reconstitution inflammatory syndrome (IRIS) after initiating antiretroviral
      therapy (ART), which is thought to result from exaggerated inflammatory antigen
      specific T cell responses. The contribution of monocytes to the
      immunopathogenesis of cryptococcal IRIS remains unclear. We compared monocyte
      subset frequencies and immune responses in HIV-infected Ugandans at time of CM
      diagnosis (IRIS-Baseline) for those who later developed CM-IRIS, controls who did
      not develop CM-IRIS (Control-Baseline) at CM-IRIS (IRIS-Event), and for controls
      at a time point matched for ART duration (Control-Event) to understand the
      association of monocyte distribution and immune responses with cryptococcal IRIS.
      At baseline, stimulation with IFN-gamma ex vivo induced a higher frequency of TNF
      alpha- and IL-6-producing monocytes among those who later developed IRIS. Among
      participants who developed IRIS, ex vivo IFN-gamma stimulation induced higher
      frequencies of activated monocytes, IL-6+, TNF-alpha+ classical, and IL-6+
      intermediate monocytes compared with controls. In conclusion, we have
      demonstrated that monocyte subset phenotype and cytokine responses prior to ART
      are associated with and may be predictive of CM-IRIS. Larger studies to further
      delineate innate immunological responses and the efficacy of immunomodulatory
      therapies during cryptococcal IRIS are warranted.

PMID- 29371547
TI  - Isolation of Ovicidal Fungi from Fecal Samples of Captive Animals Maintained in a
      Zoological Park.
AB  - Abstract: There are certain saprophytic fungi in the soil able to develop an
      antagonistic effect against eggs of parasites. Some of these fungal species are
      ingested by animals during grazing, and survive in their feces after passing
      through the digestive tract. To identify and isolate ovicidal fungi in the feces
      of wild captive animals, a total of 60 fecal samples were taken from different
      wild animals kept captive in the Marcelle Natureza Zoological Park (Lugo, Spain).
      After the serial culture of the feces onto Petri dishes with different media,
      their parasicitide activity was assayed against eggs of trematodes (Calicophoron
      daubneyi) and ascarids (Parascaris equorum). Seven fungal genera were identified
      in the feces. Isolates from Fusarium, Lecanicillium, Mucor, Trichoderma, and
      Verticillium showed an ovicidal effect classified as type 3, because of their
      ability to adhere to the eggshell, penetrate, and damage permanently the inner
      embryo. Penicillium and Gliocladium developed a type 1 effect (hyphae attach to
      the eggshell but morphological damage was not provoked). These results provide
      very interesting and useful information about fungi susceptible for being used in
      biological control procedures against parasites.

PMID- 29371548
TI  - Mode of Infection of Metarhizium spp. Fungus and Their Potential as Biological
      Control Agents.
AB  - Chemical insecticides have been commonly used to control agricultural pests,
      termites, and biological vectors such as mosquitoes and ticks. However, the
      harmful impacts of toxic chemical insecticides on the environment, the
      development of resistance in pests and vectors towards chemical insecticides, and
      public concern have driven extensive research for alternatives, especially
      biological control agents such as fungus and bacteria. In this review, the mode
      of infection of Metarhizium fungus on both terrestrial and aquatic insect larvae
      and how these interactions have been widely employed will be outlined. The
      potential uses of Metarhizium anisopliae and Metarhizium acridum biological
      control agents and molecular approaches to increase their virulence will be
      discussed.

PMID- 29371549
TI  - Macrophage Migration Is Impaired within Candida albicans Biofilms.
AB  - Candida albicans is an opportunistic fungal pathogen that infects
      immunocompromised patients. Infection control requires phagocytosis by innate
      immune cells, including macrophages. Migration towards, and subsequent
      recognition of, C. albicans fungal cell wall components by macrophages is
      critical for phagocytosis. Using live-cell imaging of phagocytosis, the
      macrophage cell line J774.1 showed enhanced movement in response to C. albicans
      cell wall mutants, particularly during the first 30 min, irrespective of the
      infection ratio. However, phagocyte migration was reduced up to 2-fold within a
      C. albicans biofilm compared to planktonic fungal cells. Biofilms formed from C.
      albicans glycosylation mutant cells also inhibited macrophage migration to a
      similar extent as wildtype Candida biofilms, suggesting that the physical
      structure of the biofilm, rather than polysaccharide matrix composition, may
      hamper phagocyte migration. These data illustrate differential macrophage
      migratory capacities, dependent upon the form of C. albicans encountered.
      Impaired migration of macrophages within a C. albicans biofilm may contribute to
      the recalcitrant nature of clinical infections in which biofilm formation occurs.

PMID- 29371550
TI  - Role of Virulence Determinants in Candida albicans' Resistance to Novel 2-bromo-2
      chloro-2-(4-chlorophenylsulfonyl)-1-phenylethanone.
AB  - We investigated the role of KEX2, SAP4-6, EFG1, and CPH1 in the virulence of
      Candida under a novel compound 2-bromo-2-chloro-2-(4-chlorophenylsulfonyl)-1
      phenylethanone (Compound 4). We examined whether the exposure of C. albicans
      cells to Compound 4, non-cytotoxic to mammalian cells, reduces their adhesion to
      the human epithelium. We next assessed whether the exposure of C. albicans cells
      to Compound 4 modulates the anti-inflammatory response (IL-10) and induces human
      macrophages to respond to the Candida cells. There was a marked reduction in the
      growth of the sap4Deltasap5Deltasap6Delta mutant cells when incubated with
      Compound 4. Under Compound 4 (minimal fungicidal concentration MFC = 0.5-16
      ug/mL): (1) wild type strain SC5314 showed a resistant phenotype with down
      regulation of the KEX2 expression; (2) the following mutants of C.albicans:
      sap4Delta, sap5Delta, sap6Delta, and cph1Delta displayed decreased susceptibility
      with the paradoxical effect and up-regulation of the KEX2 expression compared to
      SC5314; (3) the immune recognition of C. albicans by macrophages and (4) the
      stimulation of IL-10 were not blocked ex vivo. The effect of deleting KEX2 in C.
      albicans had a minor impact on the direct activation of Compound 4's antifungal
      activity. The adhesion of kex2Delta is lower than that of the wild parental
      strain SC5314, and tends to decrease if grown in the presence of a sub-endpoint
      concentration of Compound 4. Our results provide evidence that SAP4-6 play a role
      as regulators of the anti-Candida resistance to Compound 4. Compound 4
      constitutes a suitable core to be further exploited for lead optimization to
      develop potent antimycotics.

PMID- 29371551
TI  - Perstraction of Intracellular Pigments through Submerged Fermentation of
      Talaromyces spp. in a Surfactant Rich Media: A Novel Approach for Enhanced
      Pigment Recovery.
AB  - A high percentage of the pigments produced by Talaromyces spp. remains inside the
      cell, which could lead to a high product concentration inhibition. To overcome
      this issue an extractive fermentation process, perstraction, was suggested, which
      involves the extraction of the intracellular products out of the cell by using a
      two-phase system during the fermentation. The present work studied the effect of
      various surfactants on secretion of intracellular pigments produced by
      Talaromyces spp. in submerged fermentation. Surfactants used were: non-ionic
      surfactants (Tween 80, Span 20 and Triton X-100) and a polyethylene glycerol
      polymer 8000, at different concentrations (5, 20, 35 g/L). The highest
      extracellular pigment yield (16 OD500nm) was reached using Triton X-100 (35 g/L),
      which was 44% higher than the control (no surfactant added). The effect of
      addition time of the selected surfactant was further studied. The highest
      extracellular pigment concentration (22 OD500nm) was achieved when the surfactant
      was added at 120 h of fermentation. Kinetics of extracellular and intracellular
      pigments were examined. Total pigment at the end of the fermentation using Triton
      X-100 was 27.7% higher than the control, confirming that the use of surfactants
      partially alleviated the product inhibition during the pigment production
      culture.

PMID- 29371552
TI  - Production and New Extraction Method of Polyketide Red Pigments Produced by
      Ascomycetous Fungi from Terrestrial and Marine Habitats.
AB  - The use of ascomycetous fungi as pigment producers opens the way to an
      alternative to synthetic dyes, especially in the red-dye industries, which have
      very few natural pigment alternatives. The present paper aimed to bio-prospect
      and screen out 15 selected ascomycetous fungal strains, originating from
      terrestrial and marine habitats belonging to seven different genera (Penicillium,
      Talaromyces, Fusarium, Aspergillus, Trichoderma, Dreschlera, and Paecilomyces).
      We identified four strains, Penicillium purpurogenum rubisclerotium, Fusarium
      oxysporum, marine strains identified as Talaromyces spp., and Trichoderma
      atroviride, as potential red pigment producers. The extraction of the pigments is
      a crucial step, whereby the qualitative and quantitative compositions of each
      fungal extract need to be respected for reliable identification, as well as
      preserving bioactivity. Furthermore, there is a growing demand for more
      sustainable and cost-effective extraction methods. Therefore, a pressurized
      liquid extraction technique was carried out in this study, allowing a greener and
      faster extraction step of the pigments, while preserving their chemical
      structures and bioactivities in comparison to conventional extraction processes.
      The protocol was illustrated with the production of pigment extracts from P.
      purpurogenum rubisclerotium and Talaromyces spp. Extracts were analyzed by high
      performance liquid-chromatography combined with photodiode array-detection (HPLC
      DAD) and high-resolution mass spectrometry (UHPLC-HRMS). The more promising
      strain was the isolate Talaromyces spp. of marine origin. The main polyketide
      pigment produced by this strain has been characterized as N
      threoninerubropunctamine, a non-toxic red Monascus-like azaphilone pigment.

PMID- 29371553
TI  - Biodiversity of Pigmented Fungi Isolated from Marine Environment in La Reunion
      Island, Indian Ocean: New Resources for Colored Metabolites.
AB  - Marine ecosystems cover about 70% of the planet surface and are still an
      underexploited source of useful metabolites. Among microbes, filamentous fungi
      are captivating organisms used for the production of many chemical classes of
      secondary metabolites bound to be used in various fields of industrial
      application. The present study was focused on the collection, isolation,
      screening and genotyping of pigmented filamentous fungi isolated from tropical
      marine environments around La Reunion Island, Indian Ocean. About 150
      micromycetes were revived and isolated from 14 marine samples (sediments, living
      corals, coral rubble, sea water and hard substrates) collected in four different
      locations. Forty-two colored fungal isolates belonging to 16 families, 25 genera
      and 31 species were further studied depending on their ability to produce
      pigments and thus subjected to molecular identification. From gene sequence
      analysis, the most frequently identified colored fungi belong to the widespread
      Penicillium, Talaromyces and Aspergillus genera in the family Trichocomaceae (11
      species), then followed by the family Hypocreaceae (three species). This study
      demonstrates that marine biotopes in La Reunion Island, Indian Ocean, from coral
      reefs to underwater slopes of this volcanic island, shelter numerous species of
      micromycetes, from common or uncommon genera. This unstudied biodiversity comes
      along with the ability for some fungal marine inhabitants, to produce a range of
      pigments and hues.

PMID- 29371555
TI  - Assessment of the Dyeing Properties of the Pigments Produced by Talaromyces spp.
AB  - The high production yields of pigments by Talaromyces spp. and their high thermal
      stability have implied that industrial application interests may emerge in the
      food and textile industries, as they both involve subjecting the colourants to
      high temperatures. The present study aimed to assess the potential application of
      the pigments produced by Talaromyces spp. in the textile area by studying their
      dyeing properties. Dyeing studies were performed on wool. The dyeing process
      consisted of three stages: scouring, mordanting, and dyeing. Two different
      mordants (alum, A; ferric chloride, F) were tested at different concentrations on
      fabric weight (A: 5, 10, 15%; F: 10, 20, 30%). The mordanting process had a
      significant effect on the final colour of the dyed fabrics obtained. The values
      of dyeing rate constant (k), half-time of dyeing (t1/2), and sorption kinetics
      behaviour were evaluated and discussed. The obtained results showed that pigments
      produced by Talaromyces spp. could serve as a source for the natural dyeing of
      wool textiles.

PMID- 29371554
TI  - Methodological Issues in Antifungal Susceptibility Testing of Malassezia
      pachydermatis.
AB  - Reference methods for antifungal susceptibility testing of yeasts have been
      developed by the Clinical and Laboratory Standards Institute (CLSI) and the
      European Committee on Antibiotic Susceptibility Testing (EUCAST). These methods
      are intended to test the main pathogenic yeasts that cause invasive infections,
      namely Candida spp. and Cryptococcusneoformans, while testing other yeast species
      introduces several additional problems in standardization not addressed by these
      reference procedures. As a consequence, a number of procedures have been employed
      in the literature to test the antifungal susceptibility of Malassezia
      pachydermatis. This has resulted in conflicting results. The aim of the present
      study is to review the procedures and the technical parameters (growth media,
      inoculum preparation, temperature and length of incubation, method of reading)
      employed for susceptibility testing of M. pachydermatis, and when possible, to
      propose recommendations for or against their use. Such information may be useful
      for the future development of a reference assay.

PMID- 29371556
TI  - Carotenoid Biosynthesis in Fusarium.
AB  - Many fungi of the genus Fusarium stand out for the complexity of their secondary
      metabolism. Individual species may differ in their metabolic capacities, but they
      usually share the ability to synthesize carotenoids, a family of hydrophobic
      terpenoid pigments widely distributed in nature. Early studies on carotenoid
      biosynthesis in Fusariumaquaeductuum have been recently extended in Fusarium
      fujikuroi and Fusarium oxysporum, well-known biotechnological and phytopathogenic
      models, respectively. The major Fusarium carotenoid is neurosporaxanthin, a
      carboxylic xanthophyll synthesized from geranylgeranyl pyrophosphate through the
      activity of four enzymes, encoded by the genes carRA, carB, carT and carD. These
      fungi produce also minor amounts of beta-carotene, which may be cleaved by the
      CarX oxygenase to produce retinal, the rhodopsin's chromophore. The genes needed
      to produce retinal are organized in a gene cluster with a rhodopsin gene, while
      other carotenoid genes are not linked. In the investigated Fusarium species, the
      synthesis of carotenoids is induced by light through the transcriptional
      induction of the structural genes. In some species, deep-pigmented mutants with
      up-regulated expression of these genes are affected in the regulatory gene carS.
      The molecular mechanisms underlying the control by light and by the CarS protein
      are currently under investigation.

PMID- 29371557
TI  - Metabolic Interactions between Bacteria and Fungi in Commensal Oral Biofilms.
AB  - Oral health is more than just the absence of disease. The key to oral health is a
      diverse microbiome in an ecological balance. The oral microbiota is one of the
      most complex and diverse microbial communities in the human body. To maintain
      oral health, balance between the human host and the intrinsic microorganisms is
      essential. The healthy oral cavity is represented by a great microbial diversity,
      including both bacteria and fungi. The bacterial microbiome is very well studied.
      In contrast, fungi inhabiting the oral cavity are often overlooked. All microbial
      species in the oral cavity form communities which establish a variety of micro
      niches and inter- and intra-species interactions. These interactions can be
      classified into three main groups: physical, chemical and metabolic interactions.
      Different metabolic interactions are reviewed in this report, among which are the
      metabolism of sugars, carbon, lactate and oxygen. This review set out with the
      aim of assessing the importance of metabolic interactions between fungi and
      bacteria in the healthy oral cavity.

PMID- 29371559
TI  - The Effect of Novel Heterocyclic Compounds on Cryptococcal Biofilm.
AB  - Biofilm formation by microorganisms depends on their communication by quorum
      sensing, which is mediated by small diffusible signaling molecules that
      accumulate in the extracellular environment. During human infection, the
      pathogenic yeast Cryptococcus neoformans can form biofilm on medical devices,
      which protects the organism and increases its resistance to antifungal agents.
      The aim of this study was to test two novel heterocyclic compounds, S-8
      (thiazolidinedione derivative, TZD) and NA-8 (succinimide derivative, SI), for
      their anti-biofilm activity against strains of Cryptococcus neoformans and
      Cryptococcus gattii. Biofilms were formed in a defined medium in 96-well
      polystyrene plates and 8-well micro-slides. The effect of sub-inhibitory
      concentrations of S-8 and NA-8 on biofilm formation was measured after 48 h by a
      metabolic reduction assay and by confocal laser microscopy analysis using
      fluorescent staining. The formation and development of cryptococcal biofilms was
      inhibited significantly by these compounds in concentrations below the minimum
      inhibitory concentration (MIC) values. These compounds may have a potential role
      in preventing fungal biofilm development on indwelling medical devices or even as
      a therapeutic measure after the establishment of biofilm.

PMID- 29371560
TI  - Utilization of High Performance Liquid Chromatography Coupled to Tandem Mass
      Spectrometry for Characterization of 8-O-methylbostrycoidin Production by Species
      of the Fungus Fusarium.
AB  - The pigment 8-O-methylbostrycoidin is a polyketide metabolite produced by
      multiple species of the fungus Fusarium that infects plant crops, including
      maize. A technique was developed for the analysis of 8-O-methylbostrycoidin by
      high performance liquid chromatography coupled to electrospray ionization tandem
      mass spectrometry. The quantitative nature of the LC-MS/MS experiment was
      demonstrated over a range of concentrations in maize. Limits of detection for the
      method (10 ng/g from 8-O-methylbostrycoidin spiked into ground maize) were shown,
      and susceptibility of the method to matrix effects from maize was also evaluated.
      The method was applied to evaluate the ability of the maize pathogen Fusarium
      verticillioides to produce 8-O-methylbostrycoidin in developing maize ears grown
      in an agricultural field.

PMID- 29371558
TI  - Strategies to Reduce Mortality in Adult and Neonatal Candidemia in Developing
      Countries.
AB  - Candidemia, the commonest invasive fungal infection, is associated with high
      morbidity and mortality in developing countries, though the exact prevalence is
      not known due to lack of systematic epidemiological data from those countries.
      The limited studies report a very high incidence of candidemia and unique
      epidemiology with a different spectrum of Candida species. The recent global
      emergence of multi-drug resistant Candida auris is looming large as an important
      threat in hospitalized patients of developing countries. While managing
      candidemia cases in those countries several challenges are faced, which include
      poor infrastructure; compromised healthcare and infection control practices;
      misuse and overuse of antibiotics and steroids; lack of awareness in fungal
      infections; non-availability of advance diagnostic tests and antifungal drugs in
      many areas; poor compliance to antifungal therapy and stewardship program.
      Considering the above limitations, innovative strategies are required to reduce
      mortality due to candidemia in adults and neonates. In the present review, we
      have unraveled the challenges of candidemia faced by low resource countries and
      propose a ten part strategy to reduce mortality due candidemia.

PMID- 29371561
TI  - Biosynthesis of Astaxanthin as a Main Carotenoid in the Heterobasidiomycetous
      Yeast Xanthophyllomyces dendrorhous.
AB  - Carotenoids are organic lipophilic yellow to orange and reddish pigments of
      terpenoid nature that are usually composed of eight isoprene units. This group of
      secondary metabolites includes carotenes and xanthophylls, which can be naturally
      obtained from photosynthetic organisms, some fungi, and bacteria. One of the
      microorganisms able to synthesise carotenoids is the heterobasidiomycetous yeast
      Xanthophyllomyces dendrorhous, which represents the teleomorphic state of Phaffia
      rhodozyma, and is mainly used for the production of the xanthophyll astaxanthin.
      Upgraded knowledge on the biosynthetic pathway of the main carotenoids
      synthesised by X. dendrorhous, the biotechnology-based improvement of astaxanthin
      production, as well as the current omics approaches available in this yeast are
      reviewed in depth.

PMID- 29371562
TI  - Fungal Pigments: Deep into the Rainbow of Colorful Fungi.
AB  - With the impact of globalization on research trends, the search for healthier
      life styles, the increasing public demand for natural, organic, and "clean
      labelled" products, as well as the growing global market for natural colorants in
      economically fast-growing countries all over the world, filamentous fungi started
      to be investigated as readily available sources of chemically diverse pigments
      and colorants.[...].

PMID- 29371565
TI  - Innate and Adaptive Immunity to Mucorales.
AB  - Mucormycosis is an invasive fungal infection characterised by rapid filamentous
      growth, which leads to angioinvasion, thrombosis, and tissue necrosis. The high
      mortality rates (50-100%) associated with mucormycosis are reflective of not only
      the aggressive nature of the infection and the poor therapeutics currently
      employed, but also the failure of the human immune system to successfully clear
      the infection. Immune effector interaction with Mucorales is influenced by the
      developmental stage of the mucormycete spore. In a healthy immune environment,
      resting spores are resistant to phagocytic killing. Contrarily, swollen spores
      and hyphae are susceptible to damage and degradation by macrophages and
      neutrophils. Under the effects of immune suppression, the recruitment and
      efficacy of macrophage and neutrophil activity against mucormycetes is
      considerably reduced. Following penetration of the endothelial lining, Mucorales
      encounter platelets. Platelets adhere to both mucormycete spores and hyphae, and
      exhibit germination suppression and hyphal damage capacity in vitro. Dendritic
      cells are activated in response to Mucorales hyphae only, and induce adaptive
      immunity. It is crucial to further knowledge regarding our immune system's
      failure to eradicate resting spores under intact immunity and inhibit fungal
      growth under immunocompromised conditions, in order to understand mucormycosis
      pathogenicity and enhance therapeutic strategies for mucormycosis.

PMID- 29371563
TI  - Natural Antimicrobial Peptides as Inspiration for Design of a New Generation
      Antifungal Compounds.
AB  - Invasive fungal infections are associated with high mortality rates, despite
      appropriate antifungal therapy. Limited therapeutic options, resistance
      development and the high mortality of invasive fungal infections brought about
      more concern triggering the search for new compounds capable of interfering with
      fungal viability and virulence. In this context, peptides gained attention as
      promising candidates for the antimycotics development. Variety of structural and
      functional characteristics identified for various natural antifungal peptides
      makes them excellent starting points for design novel drug candidates. Current
      review provides a brief overview of natural and synthetic antifungal peptides.

PMID- 29371566
TI  - Verapamil Inhibits Aspergillus Biofilm, but Antagonizes Voriconazole.
AB  - The paucity of effective antifungals against Aspergillus and increasing
      resistance, the recognition of the importance of Aspergillus biofilm in several
      clinical settings, and reports of verapamil-a calcium channel blocker-efficacy
      against Candida biofilm and hyphal growth, and synergy with an azole antifungal
      in vitro, led to a study of verapamil +/- voriconazole against Aspergillus. Broth
      macrodilution methodology was utilized for MIC (minimum inhibitory concentration)
      and MFC (minimum fungicidal concentration) determination. The metabolic effects
      (assessed by XTT [2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5
      carboxanilide inner salt]) on biofilm formation by conidia were studied upon
      exposure to verapamil, verapamil plus voriconazole, or voriconazole alone. For
      biofilm formation, we found less inhibition from the combinations than with
      either drug alone, or less inhibition from the combination than that of the more
      potent drug alone. For preformed biofilm, we found no significant change in
      activity comparing voriconazole alone compared to added verapamil, and no
      significant alteration of activity of the more potent voriconazole, at any
      concentration in the range tested, by addition of a concentration of verapamil
      that is inhibitory alone. In full checkerboard assays with planktonic fungus,
      there was no indication of any effect of one drug on the other (indifference).
      Although verapamil was similarly inactive against planktonic Aspergillus, as with
      Candida, verapamil was indeed active against Aspergillus biofilm. However,
      indifference and antagonism was found with voriconazole.

PMID- 29371564
TI  - Immune Recognition of Fungal Polysaccharides.
AB  - The incidence of fungal infections has dramatically increased in recent years, in
      large part due to increased use of immunosuppressive medications, as well as
      aggressive medical and surgical interventions that compromise natural skin and
      mucosal barriers. There are relatively few currently licensed antifungal drugs,
      and rising resistance to these agents has led to interest in the development of
      novel preventative and therapeutic strategies targeting these devastating
      infections. One approach to combat fungal infections is to augment the host
      immune response towards these organisms. The polysaccharide-rich cell wall is the
      initial point of contact between fungi and the host immune system, and therefore,
      represents an important target for immunotherapeutic approaches. This review
      highlights the advances made in our understanding of the mechanisms by which the
      immune system recognizes and interacts with exopolysaccharides produced by four
      of the most common fungal pathogens: Aspergillus fumigatus, Candida albicans,
      Cryptococcus neoformans, and Histoplasma capsulatum. Work to date suggests that
      inner cell wall polysaccharides that play an important structural role are the
      most conserved across diverse members of the fungal kingdom, and elicit the
      strongest innate immune responses. The immune system senses these carbohydrates
      through receptors, such as lectins and complement proteins. In contrast, a
      greater diversity of polysaccharides is found within the outer cell walls of
      pathogenic fungi. These glycans play an important role in immune evasion, and can
      even induce anti-inflammatory host responses. Further study of the complex
      interactions between the host immune system and the fungal polysaccharides will
      be necessary to develop more effective therapeutic strategies, as well as to
      explore the use of immunosuppressive polysaccharides as therapeutic agents to
      modulate inflammation.

PMID- 29371568
TI  - The Role of IL-17 in Protection against Mucosal Candida Infections.
AB  - Interleukin-17 (IL-17) is a proinflammatory cytokine produced by adaptive CD4+ T
      helper cells and innate lymphocytes, such as gammadelta-T cells and TCRbeta+
      "natural" Th17 cells. IL-17 activates signaling through the IL-17 receptor, which
      induces other proinflammatory cytokines, antimicrobial peptides and neutrophil
      chemokines that are important for antifungal activity. The importance of IL-17 in
      protective antifungal immunity is evident in mice and humans, where various
      genetic defects related to the IL-17-signaling pathway render them highly
      susceptible to forms of candidiasis such oropharyngeal candidiasis (OPC) or more
      broadly chronic mucocutaneous candidiasis (CMC), both caused mainly by the
      opportunistic fungal pathogen Candida albicans. OPC is common in infants and the
      elderly, HIV/AIDS and patients receiving chemotherapy and/or radiotherapy for
      head and neck cancers. This review focuses on the role of IL-17 in protection
      against candidiasis, and includes a brief discussion of non-Candida albicans
      fungal infections, as well as how therapeutic interventions blocking IL-17
      related components can affect antifungal immunity.

PMID- 29371569
TI  - Cryptococcus-Epithelial Interactions.
AB  - The fungal pathogen, Cryptococcus neoformans, causes devastating levels of
      morbidity and mortality. Infections with this fungus tend to be predominantly in
      immunocompromised individuals, such as those with HIV. Infections initiate with
      inhalation of cryptococcal cells and entry of the pathogen into the lungs. The
      bronchial epithelial cells of the upper airway and the alveolar epithelial cells
      of the lower airway are likely to be the first host cells that Cryptococcus
      engage with. Thus the interaction of cryptococci and the respiratory epithelia
      will be the focus of this review. C. neoformans has been shown to adhere to
      respiratory epithelial cells, although if the role of the capsule is in aiding or
      hindering this adhesion is debatable. The epithelia are also able to react to
      cryptococci with the release of cytokines and chemokines to start the immune
      response to this invading pathogen. The activity of surfactant components that
      line this mucosal barrier towards Cryptococcus and the metabolic and
      transcriptional reaction of cryptococci when encountering epithelial cells will
      also be discussed.

PMID- 29371567
TI  - Fungal Strategies to Evade the Host Immune Recognition.
AB  - The recognition of fungal cells by the host immune system is key during the
      establishment of a protective anti-fungal response. Even though the immune system
      has evolved a vast number of processes to control these organisms, they have
      developed strategies to fight back, avoiding the proper recognition by immune
      components and thus interfering with the host protective mechanisms. Therefore,
      the strategies to evade the immune system are as important as the virulence
      factors and attributes that damage the host tissues and cells. Here, we performed
      a thorough revision of the main fungal tactics to escape from the host
      immunosurveillance processes. These include the composition and organization of
      the cell wall, the fungal capsule, the formation of titan cells, biofilms, and
      asteroid bodies; the ability to undergo dimorphism; and the escape from
      nutritional immunity, extracellular traps, phagocytosis, and the action of
      humoral immune effectors.

PMID- 29371570
TI  - A Novel Assay Reveals a Maturation Process during Ascospore Wall Formation.
AB  - The ascospore wall of the budding yeast Saccharomyces cerevisiae consists of
      inner layers of similar composition to the vegetative cell wall and outer layers
      made of spore-specific components that confer increased stress resistance on the
      spore. The primary constituents of the outer spore wall are chitosan, dityrosine,
      and a third component termed Chi that has been identified by spectrometry but
      whose chemical structure is not known. The lipophilic dye monodansylpentane
      readily stains lipid droplets inside of newly formed ascospores but, over the
      course of several days, the spores become impermeable to the dye. The generation
      of this permeability barrier requires the chitosan layer, but not dityrosine
      layer, of the spore wall. Screening of a set of mutants with different outer
      spore wall defects reveals that impermeability to the dye requires not just the
      presence of chitosan, but another factor as well, possibly Chi, and suggests that
      the OSW2 gene product is required for synthesis of this factor. Testing of
      mutants that block synthesis of specific aromatic amino acids indicates that de
      novo synthesis of tyrosine contributes not only to formation of the dityrosine
      layer but to impermeability of the wall as well, suggesting a second role for
      aromatic amino acids in spore wall synthesis.

PMID- 29371571
TI  - The Multifaceted Role of T-Helper Responses in Host Defense against Aspergillus
      fumigatus.
AB  - The ubiquitous opportunistic fungal pathogen Aspergillus fumigatus rarely causes
      infections in immunocompetent individuals. A healthy functional innate immune
      system plays a crucial role in preventing Aspergillus-infection. This pivotal
      role for the innate immune system makes it a main research focus in studying the
      pathogenesis of aspergillosis. Although sometimes overshadowed by the innate
      immune response, the adaptive immune response, and in particular T-helper
      responses, also represents a key player in host defense against Aspergillus.
      Virtually all T-helper subsets have been described to play a role during
      aspergillosis, with the Th1 response being crucial for fungal clearance. However;
      morbidity and mortality of aspergillosis can also be partly attributed to
      detrimental immune responses resulting from adaptive immune activation. Th2
      responses benefit fungal persistence; and are the foundation of allergic forms of
      aspergillosis. The Th17 response has two sides; although crucial for granulocyte
      recruitment, it can be involved in detrimental immunopathology. Regulatory T
      cells, the endogenous regulators of inflammatory responses, play a key role in
      controlling detrimental inflammatory responses during aspergillosis. The current
      knowledge of the adaptive immune response against A. fumigatus is summarized in
      this review. A better understanding on how T-helper responses facilitate
      clearance of Aspergillus-infection and control inflammation can be the
      fundamental basis for understanding the pathogenesis of aspergillosis and for the
      development of novel host-directed therapies.

PMID- 29371572
TI  - The Human Mucosal Mycobiome and Fungal Community Interactions.
AB  - With the advent of high-throughput sequencing techniques, the astonishing extent
      and complexity of the microbial communities that reside within and upon us has
      begun to become clear. Moreover, with advances in computing and modelling
      methods, we are now beginning to grasp just how dynamic our interactions with
      these communities are. The diversity of both these communities and their
      interactions-both within the community and with us-are dependent on a multitude
      of factors, both microbial- and host-mediated. Importantly, it is becoming clear
      that shifts in the makeup of these communities, or their responses, are linked to
      different disease states. Although much of the work to define these interactions
      and links has been investigating bacterial communities, recently there has been
      significant growth in the body of knowledge, indicating that shifts in the host
      fungal communities (mycobiome) are also intimately linked to disease status. In
      this review, we will explore these associations, along with the interactions
      between fungal communities and their human and microbial habitat, and discuss the
      future applications of systems biology in determining their role in disease
      status.

PMID- 29371574
TI  - Fungicidal Activity in the Presence of Keratin as an Important Factor
      Contributing to In Vivo Efficacy: A Comparison of Efinaconazole, Tavaborole, and
      Ciclopirox.
AB  - Use of oral antifungals in the treatment of onychomycosis is commonplace; but
      their use can be limited by safety and patient concerns. Due to their broader
      safety margins, topical antifungals (efinaconazole, tavaborole, and ciclopirox)
      are a useful option in the treatment of mild-to-moderate onychomycosis in the
      USA, but their antifungal activity has yet to be directly compared. This study
      aims to identify important factors contributing to in vivo efficacies of the
      three topical antifungals. Minimum inhibitory concentrations (MICs) were
      determined by Clinical and Laboratory Standards Institute (CLSI) M38-A2 broth
      microdilution. The MIC90 values of efinaconazole, tavaborole, and ciclopirox for
      T. rubrum were 0.0078, 8.0, and 0.50 MUg/mL, respectively. The MIC90 values for
      T. mentagrophytes were 0.016, 8.0, and 0.50 MUg/mL, respectively. Efinaconazole
      showed potent fungicidal activity in keratin-containing medium, whereas
      tavaborole was fungistatic, and ciclopirox not active. In the guinea pig model of
      onychomycosis, the therapeutic efficacy of efinaconazole was superior to those of
      tavaborole and ciclopirox. This study suggests that not only fungistatic activity
      (MIC), but also fungicidal activity in the presence of keratin, is an important
      factor contributing to the in vivo efficacy of topical antifungal drugs against
      onychomycosis.

PMID- 29371573
TI  - Global and Multi-National Prevalence of Fungal Diseases-Estimate Precision.
AB  - Fungal diseases kill more than 1.5 million and affect over a billion people.
      However, they are still a neglected topic by public health authorities even
      though most deaths from fungal diseases are avoidable. Serious fungal infections
      occur as a consequence of other health problems including asthma, AIDS, cancer,
      organ transplantation and corticosteroid therapies. Early accurate diagnosis
      allows prompt antifungal therapy; however this is often delayed or unavailable
      leading to death, serious chronic illness or blindness. Recent global estimates
      have found 3,000,000 cases of chronic pulmonary aspergillosis, ~223,100 cases of
      cryptococcal meningitis complicating HIV/AIDS, ~700,000 cases of invasive
      candidiasis, ~500,000 cases of Pneumocystis jirovecii pneumonia, ~250,000 cases
      of invasive aspergillosis, ~100,000 cases of disseminated histoplasmosis, over
      10,000,000 cases of fungal asthma and ~1,000,000 cases of fungal keratitis occur
      annually. Since 2013, the Leading International Fungal Education (LIFE) portal
      has facilitated the estimation of the burden of serious fungal infections country
      by country for over 5.7 billion people (>80% of the world's population). These
      studies have shown differences in the global burden between countries, within
      regions of the same country and between at risk populations. Here we interrogate
      the accuracy of these fungal infection burden estimates in the 43 published
      papers within the LIFE initiative.

PMID- 29371575
TI  - The PHR Family: The Role of Extracellular Transglycosylases in Shaping Candida
      albicans Cells.
AB  - Candida albicans is an opportunistic microorganism that can become a pathogen
      causing mild superficial mycosis or more severe invasive infections that can be
      life-threatening for debilitated patients. In the etiology of invasive
      infections, key factors are the adaptability of C. albicans to the different
      niches of the human body and the transition from a yeast form to hypha. Hyphal
      morphology confers high adhesiveness to the host cells, as well as the ability to
      penetrate into organs. The cell wall plays a crucial role in the morphological
      changes C. albicans undergoes in response to specific environmental cues. Among
      the different categories of enzymes involved in the formation of the fungal cell
      wall, the GH72 family of transglycosylases plays an important assembly role.
      These enzymes cut and religate beta-(1,3)-glucan, the major determinant of cell
      shape. In C. albicans, the PHR family encodes GH72 enzymes, some of which work in
      specific environmental conditions. In this review, we will summarize the work
      from the initial discovery of PHR genes to the study of the pH-dependent
      expression of PHR1 and PHR2, from the characterization of the gene products to
      the recent findings concerning the stress response generated by the lack of GH72
      activity in C. albicans hyphae.

PMID- 29371576
TI  - Innate Immunity to Mucosal Candida Infections.
AB  - Mucosal epithelial tissues are exposed to high numbers of microbes, including
      commensal fungi, and are able to distinguish between those that are avirulent and
      those that cause disease. Epithelial cells have evolved multiple mechanisms to
      defend against colonization and invasion by Candida species. The interplay
      between mucosal epithelial tissues and immune cells is key for control and
      clearance of fungal infections. Our understanding of the mucosal innate host
      defense system has expanded recently with new studies bringing to light the
      importance of epithelial cell responses, innate T cells, neutrophils, and other
      phagocytes during Candida infections. Epithelial tissues release cytokines, host
      defense peptides, and alarmins during Candida invasion that act in concert to
      limit fungal proliferation and recruit immune effector cells. The innate T
      cell/IL-17 axis and recruitment of neutrophils are of central importance in
      controlling mucosal fungal infections. Here, we review current knowledge of the
      innate immunity at sites of mucosal Candida infection, with a focus on infections
      caused by C. albicans.

PMID- 29371579
TI  - Function and Biosynthesis of Cell Wall alpha-1,3-Glucan in Fungi.
AB  - Although alpha-1,3-glucan is a major cell wall polysaccharide in filamentous
      fungi, its biological functions remain unclear, except that it acts as a
      virulence factor in animal and plant pathogenic fungi: it conceals cell wall beta
      glucan on the fungal cell surface to circumvent recognition by hosts. However,
      cell wall alpha-1,3-glucan is also present in many of non-pathogenic fungi.
      Recently, the universal function of alpha-1,3-glucan as an aggregation factor has
      been demonstrated. Applications of fungi with modified cell wall alpha-1,3-glucan
      in the fermentation industry and of in vitro enzymatically-synthesized alpha-1,3
      glucan in bio-plastics have been developed. This review focuses on the recent
      progress in our understanding of the biological functions and biosynthetic
      mechanism of cell wall alpha-1,3-glucan in fungi. We briefly consider the history
      of studies on alpha-1,3-glucan, overview its biological functions and
      biosynthesis, and finally consider the industrial applications of fungi deficient
      in alpha-1,3-glucan.

PMID- 29371580
TI  - Botanicals and Phosphonate Show Potential to Replace Copper for Control of Potato
      Late Blight.
AB  - Potato late blight (PLB) caused by Phytophthora infestans (Pi) is the most
      harmful disease in potato production worldwide. In organic farming, copper is
      used despite its persistence in soil and toxicity to soil organisms. To replace
      copper, suspensions of powders from three promising botanicals, including bark of
      buckthorn (Frangula alnus, FA), roots of medicinal rhubarb (Rheum palmatum) and
      galls of the nutgall tree (Galla chinensis), were tested in multi-year field
      experiments. The current study shows for the first time that botanicals could
      replace copper under field conditions and best PLB reduction on leaves was
      achieved with FA, reaching a level close to that of 2 to 3 kg copper per hectare
      and year. Better results than with copper were achieved with Phosfik(r) (Ph), a
      phosphonate-based product. For both FA and Ph, the mode of action is based on
      induced resistance, for Ph also on direct fungicidal effects. A disadvantage of
      Ph is the accumulation of residues in potato tubers. Nevertheless, two to three
      applications with 2 to 3 L/ha of Ph would be feasible to not exceed a minimal
      risk level (MLR) of 20 mg/kg of phosphorous acid as proposed by the European Food
      Safety Authority. Due to an excellent environmental profile and a complex mode of
      action counteracting Pi resistance, phosphonate-based products would be most
      suitable for sustainable PLB management in integrated pest management (IPM)
      programmes.

PMID- 29371577
TI  - MCC/Eisosomes Regulate Cell Wall Synthesis and Stress Responses in Fungi.
AB  - The fungal plasma membrane is critical for cell wall synthesis and other
      important processes including nutrient uptake, secretion, endocytosis,
      morphogenesis, and response to stress. To coordinate these diverse functions, the
      plasma membrane is organized into specialized compartments that vary in size,
      stability, and composition. One recently identified domain known as the Membrane
      Compartment of Can1 (MCC)/eisosome is distinctive in that it corresponds to a
      furrow-like invagination in the plasma membrane. MCC/eisosomes have been shown to
      be formed by the Bin/Amphiphysin/Rvs (BAR) domain proteins Lsp1 and Pil1 in a
      range of fungi. MCC/eisosome domains influence multiple cellular functions; but a
      very pronounced defect in cell wall synthesis has been observed for mutants with
      defects in MCC/eisosomes in some yeast species. For example, Candida albicans
      MCC/eisosome mutants display abnormal spatial regulation of cell wall synthesis,
      including large invaginations and altered chemical composition of the walls.
      Recent studies indicate that MCC/eisosomes affect cell wall synthesis in part by
      regulating the levels of the key regulatory lipid phosphatidylinositol 4,5
      bisphosphate (PI4,5P2) in the plasma membrane. One general way MCC/eisosomes
      function is by acting as protected islands in the plasma membrane, since these
      domains are very stable. They also act as scaffolds to recruit >20 proteins.
      Genetic studies aimed at defining the function of the MCC/eisosome proteins have
      identified important roles in resistance to stress, such as resistance to
      oxidative stress mediated by the flavodoxin-like proteins Pst1, Pst2, Pst3 and
      Ycp4. Thus, MCC/eisosomes play multiple roles in plasma membrane organization
      that protect fungal cells from the environment.

PMID- 29371578
TI  - Ecoepidemiology of Cryptococcus gattii in Developing Countries.
AB  - Cryptococcosis is a systemic infection caused by species of the encapsulated
      yeast Cryptococcus. The disease may occur in immunocompromised and
      immunocompetent hosts and is acquired by the inhalation of infectious propagules
      present in the environment. Cryptococcus is distributed in a plethora of
      ecological niches, such as soil, pigeon droppings, and tree hollows, and each
      year new reservoirs are discovered, which helps researchers to better understand
      the epidemiology of the disease. In this review, we describe the ecoepidemiology
      of the C. gattii species complex focusing on clinical cases and ecological
      reservoirs in developing countries from different continents. We also discuss
      some important aspects related to the antifungal susceptibility of different
      species within the C. gattii species complex and bring new insights on the
      revised Cryptococcus taxonomy.

PMID- 29371581
TI  - HIV-Associated Cryptococcal Disease in Resource-Limited Settings: A Case for
      "Prevention Is Better Than Cure"?
AB  - Cryptococcal disease remains a significant source of global morbidity and
      mortality for people living with HIV, especially in resource-limited settings.
      The recently updated estimate of cryptococcal disease revealed a global incidence
      of 223,100 cases annually with 73% of these cases being diagnosed in sub-Saharan
      Africa. Furthermore, 75% of the estimated 181,100 deaths associated with
      cryptococcal disease occur in sub-Saharan Africa. Point-of-care diagnostic assays
      have revolutionised the diagnosis of this deadly opportunistic infection. The
      theory of asymptomatic cryptococcal antigenaemia as a forerunner to symptomatic
      meningitis and death has been conclusively proven. Thus, cryptococcal
      antigenaemia screening coupled with pre-emptive antifungal therapy has been
      demonstrated as a cost-effective strategy with survival benefits and has been
      incorporated into HIV national guidelines in several countries. However, this is
      yet to be implemented in a number of other high HIV burden countries. Flucytosine
      based combination therapy during the induction phase is associated with improved
      survival, faster cerebrospinal fluid sterilisation and fewer relapses.
      Flucytosine, however, is unavailable in many parts of the world. Studies are
      ongoing on the efficacy of shorter regimens of amphotericin B. Early diagnosis,
      proactive antifungal therapy with concurrent management of raised intracranial
      pressure creates the potential to markedly reduce mortality associated with this
      disease.

PMID- 29371582
TI  - The Cell Wall Integrity Signaling Pathway and Its Involvement in Secondary
      Metabolite Production.
AB  - The fungal cell wall is the external and first layer that fungi use to interact
      with the environment. Every stress signal, before being translated into an
      appropriate stress response, needs to overtake this layer. Many signaling
      pathways are involved in translating stress signals, but the cell wall integrity
      (CWI) signaling pathway is the one responsible for the maintenance and
      biosynthesis of the fungal cell wall. In fungi, the CWI signal is composed of a
      mitogen-activated protein kinase (MAPK) module. After the start of the
      phosphorylation cascade, the CWI signal induces the expression of cell-wall
      related genes. However, the function of the CWI signal is not merely the
      activation of cell wall biosynthesis, but also the regulation of expression and
      production of specific molecules that are used by fungi to better compete in the
      environment. These molecules are normally defined as secondary metabolites or
      natural products. This review is focused on secondary metabolites affected by the
      CWI signal pathway with a special focus on relevant natural products such as
      melanins, mycotoxins, and antibacterial compounds.

PMID- 29371583
TI  - Fluconazole Resistance among Oral Candida Isolates from People Living with
      HIV/AIDS in a Nigerian Tertiary Hospital.
AB  - Oropharyngeal candidiasis, a common fungal infection in people living with
      HIV/AIDS (PLWHA), arises from Candida species colonizing the oral cavity.
      Fluconazole is the preferred treatment and is often used empirically. Few studies
      have investigated the prevalence of fluconazole resistance in Nigeria. This study
      aimed at determining the burden of fluconazole resistance among Candida species
      in the oral cavities of PLWHA. We sampled the oral cavities of 350 HIV-infected
      adults and an equal number of HIV-negative controls. Candida isolates were
      identified using germ tube tests, CHROMagar Candida (CHROMagar, Paris, France),
      and API Candida yeast identification system (BioMerieux, Marcy-l'Etoile, France).
      Fluconazole susceptibility was determined using the Clinical and Laboratory
      Standards Institute disc diffusion method. Data were analysed using SPSS version
      21 (IBM, New York, NY, USA). The significance level was set at p <= 0.05. The
      isolation rates for Candida amongst HIV-infected subjects and controls were 20.6%
      and 3.4%, respectively (p < 0.001). In PLWHA, Candida albicans was most
      frequently isolated (81.3%) and fluconazole resistance was present in 18 (24%) of
      the 75 Candida isolates. Resistance to fluconazole was present in half of the non
      albicans Candida isolates. Fluconazole resistance is prevalent among oral Candida
      isolates in PLWHA in the study area with a significantly higher rate among non
      albicans Candida spp.

PMID- 29371584
TI  - Hemorrhagic Brain Metastases in a Patient with Anaplastic Lymphoma Kinase (ALK)
      Rearranged Invasive Mucinous Adenocarcinoma of the Lung.
AB  - BACKGROUND Invasive mucinous adenocarcinoma (IMA) is a rare variant of
      adenocarcinoma of the lung. It frequently shows KRAS mutations, while ALK
      rearrangement is exceedingly rare. We present a case of ALK-rearranged IMA of the
      lung presenting with an unusual pattern of brain metastases, radiologically
      mimicking a cavernous angioma. CASE REPORT A 44-year-old non-smoker female was
      first diagnosed with lung right lower lobe IMA with ALK rearrangement. Five years
      after surgery followed by chemotherapy, she developed a sudden onset headache.
      Brain imaging revealed a hemorrhagic left frontal mass, suspicious for a
      cavernous angioma. However, the pathology of the resected lesion showed an ALK
      rearranged brain metastasis from the IMA of the lung. Interestingly, the
      metastases showed perivascular tumor infiltrates, accompanied by focal mural
      invasion, vascular disruption, and hemorrhage. CONCLUSIONS To our knowledge, this
      is the first reported case of brain metastasis from an ALK-rearranged IMA of the
      lung. Further investigation of the clinical and pathological characteristics of
      the ALK-rearranged IMA, including awareness of the possibility for development of
      brain metastases with tumor-associated vasculopathy and hemorrhage, is warranted.

PMID- 29371585
TI  - Biomechanical Stability of a Cross-Rod Connection with a Pedicle Screw System.
AB  - BACKGROUND Surgery with pedicle screw instrumentation does not provide sufficient
      torsional stability. This leads to pseudoarthrosis, loosening of the pedicle
      screws, and, ultimately, implant failure. MATERIAL AND METHODS Functional spinal
      units from 18 deer were evaluated using a 6-axis material testing machine. As
      specimen models, we prepared an intact model, a damaged model, a cross-rod model,
      and a cross-link model. We measured the range of motion (ROM) during bending and
      rotation tests. RESULTS The range of motions of cross-rod model were almost equal
      to those of cross-link model during the bending test. In the rotation test, the
      average ranges of motion of the intact, cross-rod, and cross-link models were 2.9
      degrees , 3.1 degrees , and 3.9 degrees  during right rotation and 2.9 degrees ,
      3.1 degrees , and 4.1 degrees  during left rotation, respectively. The range of
      motions of the cross-rod model were significantly smaller than those of the cross
      link model during the rotation test. The range of motions of the intact model
      were significantly smaller than those of the cross-link model during the rotation
      test, but there were no statistically significant differences between the range
      of motions of intact model and cross-rod model during the rotation test.
      CONCLUSIONS The stability of spinal fixation such as cross-rod model is equal to
      the fixation using the pedicle screw system during bending tests and equal to
      that of the intact spine during rotation tests.

PMID- 29371586
TI  - Short-Term Outcomes Using a Drug-Coated Balloon for Transplant Renal Artery
      Stenosis.
AB  - BACKGROUND This study aimed to evaluate the early and mid-term outcomes of drug
      coated balloon (DCB) use in patients who underwent intervention for transplant
      renal artery stenosis (TRAS). MATERIAL AND METHODS We retrospectively reviewed
      the records of TRAS patients who received endovascular therapy with DCB in our
      institution from March 2016 to January 2017. Statistical analysis of pre
      /postoperative levels of serum creatinine (Scr), systolic blood pressure (SBP),
      and renal artery peak systolic velocities (PSV) were performed. RESULTS Fourteen
      patients presenting with TRAS, which were mostly located at the anastomosis (n=9)
      and transplanted artery proximal portion (n=2), were treated with DCB. Three TRAS
      patients with in-stent restenosis (ISR) were also included in the series. The
      procedure technique success rate was 100%. The mean follow-up time was 8.6
      months. The Scr level decreased from 481.8 umol/L (208.5-746.2umol/L) pre
      operation to 154umol/L (89.1-301.2 umol/L, p<0.01) at 1 month post-intervention.
      The SBP varied from 161.4 mmHg (152-173 mmHg) to 144.8 mmHg (136-154 mmHg,
      p<0.01). Renal artery PSV decreased from 364.1 cm/s (217.6-511.9 cm/s) to 134.9
      cm/s (79.8-184.2 cm/s, p<0.01). Eleven patients finished mid-term (>6 months)
      follow-up. The statistical results were not significant compared to those at 1
      month, although they all slightly decreased. No re-intervention was performed.
      CONCLUSIONS The endovascular approach to TRAS with DCB was a safe and effective
      treatment for restore and maintain the artery flow and renal function in short
      term follow-up.

PMID- 29371587
TI  - The Role of miR-126 in Critical Limb Ischemia Treatment Using Adipose-Derived
      Stem Cell Therapeutic Factor Concentrate and Extracellular Matrix Microparticles.
AB  - BACKGROUND Paracrine factors secreted by adipose-derived stem cells can be
      captured, fractionated, and concentrated to produce therapeutic factor
      concentrate (TFC). The present study examined whether TFC effects could be
      enhanced by combining TFC with a biological matrix to provide sustained release
      of factors in the target region. MATERIAL AND METHODS Unilateral hind limb
      ischemia was induced in rabbits. Ischemic limbs were injected with either placebo
      control, TFC, micronized small intestinal submucosa tissue (SIS), or TFC absorbed
      to SIS. Blood flow in both limbs was assessed with laser Doppler perfusion
      imaging. Tissues harvested at Day 48 were assessed immunohistochemically for
      vessel density; in situ hybridization and quantitative real-time PCR were
      employed to determine miR-126 expression. RESULTS LDP ratios were significantly
      elevated, compared to placebo control, on day 28 in all treatment groups
      (p=0.0816, p=0.0543, p=0.0639, for groups 2-4, respectively) and on day 36 in the
      TFC group (p=0.0866). This effect correlated with capillary density in the SIS
      and TFC+SIS groups (p=0.0093 and p=0.0054, respectively, compared to placebo). A
      correlation was observed between miR-126 levels and LDP levels at 48 days in SIS
      and TFC+SIS groups. CONCLUSIONS A single bolus administration of TFC and SIS had
      early, transient effects on reperfusion and promotion of ischemia repair. The
      effects were not additive. We also discovered that TFC modulated miR-126 levels
      that were expressed in cell types other than endothelial cells. These data
      suggested that TFC, alone or in combination with SIS, may be a potent therapy for
      patients with CLI that are at risk of amputation.

PMID- 29371590
TI  - Cell death-based treatment of glioblastoma.
AB  - Cancer cells including glioblastoma have typically evolved multiple mechanisms to
      escape programmed cell death in order to maintain their survival. Defects in cell
      death mechanisms not only facilitate tumorigenesis but also ensure resistance to
      current anticancer therapies. This emphasizes that targeting cell death pathways
      may provide a means to tackle one of the Achilles' heels of cancer. Over the last
      decades several approaches have been developed to selectively target cell death
      pathways for therapeutic purposes. Some of these concepts have already been
      transferred into clinical application in oncology and may open new perspectives
      for the treatment of cancer.

PMID- 29371589
TI  - Cell death-based treatment of lung adenocarcinoma.
AB  - The most common type of lung cancer is adenocarcinoma (ADC), comprising around
      40% of all lung cancer cases. In spite of achievements in understanding the
      pathogenesis of this disease and the development of new approaches in its
      treatment, unfortunately, lung ADC is still one of the most aggressive and
      rapidly fatal tumor types with overall survival less than 5 years. Lung ADC is
      often diagnosed at advanced stages involving disseminated metastatic tumors. This
      is particularly important for the successful development of new approaches in
      cancer therapy. The high resistance of lung ADC to conventional radiotherapies
      and chemotherapies represents a major challenge for treatment effectiveness. Here
      we discuss recent advances in understanding the molecular pathways driving tumor
      progression and related targeted therapies in lung ADCs. In addition, the cell
      death mechanisms induced by different treatment strategies and their contribution
      to therapy resistance are analyzed. The focus is on approaches to overcoming drug
      resistance in order to improve future treatment decisions.

PMID- 29371588
TI  - Cell death-based treatment of neuroblastoma.
AB  - Neuroblastoma (NB) is the most common solid childhood tumor outside the brain and
      causes 15% of childhood cancer-related mortality. The main drivers of NB
      formation are neural crest cell-derived sympathoadrenal cells that undergo
      abnormal genetic arrangements. Moreover, NB is a complex disease that has high
      heterogeneity and is therefore difficult to target for successful therapy. Thus,
      a better understanding of NB development helps to improve treatment and increase
      the survival rate. One of the major causes of sporadic NB is known to be MYCN
      amplification and mutations in ALK (anaplastic lymphoma kinase) are responsible
      for familial NB. Many other genetic abnormalities can be found; however, they are
      not considered as driver mutations, rather they support tumor aggressiveness.
      Tumor cell elimination via cell death is widely accepted as a successful
      technique. Therefore, in this review, we provide a thorough overview of how
      different modes of cell death and treatment strategies, such as immunotherapy or
      spontaneous regression, are or can be applied for NB elimination. In addition,
      several currently used and innovative approaches and their suitability for
      clinical testing and usage will be discussed. Moreover, significant attention
      will be given to combined therapies that show more effective results with fewer
      side effects than drugs targeting only one specific protein or pathway.

PMID- 29371591
TI  - MIF inhibits the formation and toxicity of misfolded SOD1 amyloid aggregates:
      implications for familial ALS.
AB  - Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis
      (ALS), a fatal neurodegenerative disease caused by the progressive loss of motor
      neurons in the brain and spinal cord. It has been suggested that toxicity of
      mutant SOD1 results from its misfolding, however, it is yet unclear why misfolded
      SOD1 accumulates specifically within motor neurons. We recently demonstrated that
      macrophage migration inhibitory factor (MIF)-a multifunctional protein with
      cytokine/chemokine activity and cytosolic chaperone-like properties-inhibits the
      accumulation of misfolded SOD1. Here, we show that MIF inhibits mutant SOD1
      nuclear clearance when overexpressed in motor neuron-like NSC-34 cells. In
      addition, MIF alters the typical SOD1 amyloid aggregation pathway in vitro, and,
      instead, promotes the formation of disordered aggregates, as measured by
      Thioflavin T (ThT) assay and transmission electron microscopy (TEM) imaging.
      Moreover, we report that MIF reduces the toxicity of misfolded SOD1 by directly
      interacting with it, and that the chaperone function and protective effect of MIF
      in neuronal cultures do not require its intrinsic catalytic activities.
      Importantly, we report that the locked-trimeric MIFN110C mutant, which exhibits
      strongly impaired CD74-mediated cytokine functions, has strong chaperone
      activity, dissociating, for the first time, these two cellular functions.
      Altogether, our study implicates MIF as a potential therapeutic candidate in the
      treatment of ALS.

PMID- 29371592
TI  - Regulatory B cells: the cutting edge of immune tolerance in kidney
      transplantation.
AB  - Kidney transplantation is the optimal treatment for end-stage renal diseases.
      Although great improvement has been achieved, immune tolerance is still the Holy
      Grail that every organ transplant practitioner pursues. The role of B cells in
      transplantation has long been considered simply to serve as precursors of plasma
      cells, which produce alloantibodies and induce antibody-mediated rejection.
      Recent research indicates that a specialized subset of B cells plays an important
      role in immune regulation, which has been well demonstrated in autoimmune
      diseases, infections, and cancers. This category of regulatory B cells (Bregs)
      differs from conventional B cells, and they may help develop a novel
      immunomodulatory therapeutic strategy to achieve immune tolerance in
      transplantation. Here, we review the latest evidence regarding phenotypes,
      functions, and effectors of Bregs and discuss their diverse effects on kidney
      transplantation.

PMID- 29371593
TI  - Highly-efficient quantum memory for polarization qubits in a spatially
      multiplexed cold atomic ensemble.
AB  - Quantum memory for flying optical qubits is a key enabler for a wide range of
      applications in quantum information. A critical figure of merit is the overall
      storage and retrieval efficiency. So far, despite the recent achievements of
      efficient memories for light pulses, the storage of qubits has suffered from
      limited efficiency. Here we report on a quantum memory for polarization qubits
      that combines an average conditional fidelity above 99% and efficiency around
      68%, thereby demonstrating a reversible qubit mapping where more information is
      retrieved than lost. The qubits are encoded with weak coherent states at the
      single-photon level and the memory is based on electromagnetically-induced
      transparency in an elongated laser-cooled ensemble of cesium atoms, spatially
      multiplexed for dual-rail storage. This implementation preserves high optical
      depth on both rails, without compromise between multiplexing and storage
      efficiency. Our work provides an efficient node for future tests of quantum
      network functionalities and advanced photonic circuits.

PMID- 29371594
TI  - Endothelial deletion of Ino80 disrupts coronary angiogenesis and causes
      congenital heart disease.
AB  - During development, the formation of a mature, well-functioning heart requires
      transformation of the ventricular wall from a loose trabecular network into a
      dense compact myocardium at mid-gestation. Failure to compact is associated in
      humans with congenital diseases such as left ventricular non-compaction (LVNC).
      The mechanisms regulating myocardial compaction are however still poorly
      understood. Here, we show that deletion of the Ino80 chromatin remodeler in
      vascular endothelial cells prevents ventricular compaction in the developing
      mouse heart. This correlates with defective coronary vascularization, and
      specific deletion of Ino80 in the two major coronary progenitor tissues-sinus
      venosus and endocardium-causes intermediate phenotypes. In vitro, endothelial
      cells promote myocardial expansion independently of blood flow in an Ino80
      dependent manner. Ino80 deletion increases the expression of E2F-activated genes
      and endothelial cell S-phase occupancy. Thus, Ino80 is essential for coronary
      angiogenesis and allows coronary vessels to support proper compaction of the
      heart wall.

PMID- 29371595
TI  - Defining the role of the tumor vasculature in antitumor immunity and
      immunotherapy.
AB  - It is now well established that cancer cells co-exist within a complex
      environment with stromal cells and depend for their growth and dissemination on
      tight and plastic interactions with components of the tumor microenvironment
      (TME). Cancer cells incite the formation of new blood and lymphatic vessels from
      preexisting vessels to cope with their high nutrient/oxygen demand and favor
      tumor outgrowth. Research over the past decades has highlighted the crucial role
      played by tumor-associated blood and lymphatic vasculature in supporting
      immunoevasion and in subverting T-cell-mediated immunosurveillance, which are the
      main hallmarks of cancers. The structurally and functionally aberrant tumor
      vasculature contributes to the protumorigenic and immunosuppressive TME by
      maintaining a cancer cell's permissive environment characterized by hypoxia,
      acidosis, and high interstitial pressure, while simultaneously generating a
      physical barrier to T cells' infiltration. Recent research moreover has shown
      that blood endothelial cells forming the tumor vessels can actively suppress the
      recruitment, adhesion, and activity of T cells. Likewise, during tumorigenesis
      the lymphatic vasculature undergoes dramatic remodeling that facilitates
      metastatic spreading of cancer cells and immunosuppression. Beyond
      carcinogenesis, the erratic tumor vasculature has been recently implicated in
      mechanisms of therapy resistance, including those limiting the efficacy of
      clinically approved immunotherapies, such as immune checkpoint blockers and
      adoptive T-cell transfer. In this review, we discuss emerging evidence
      highlighting the major role played by tumor-associated blood and lymphatic
      vasculature in thwarting immunosurveillance mechanisms and antitumor immunity.
      Moreover, we also discuss novel therapeutic approaches targeting the tumor
      vasculature and their potential to help overcoming immunotherapy resistance.

PMID- 29371596
TI  - Multiple signaling kinases target Mrc1 to prevent genomic instability triggered
      by transcription-replication conflicts.
AB  - Conflicts between replication and transcription machineries represent a major
      source of genomic instability and cells have evolved strategies to prevent such
      conflicts. However, little is known regarding how cells cope with sudden
      increases of transcription while replicating. Here, we report the existence of a
      general mechanism for the protection of genomic integrity upon transcriptional
      outbursts in S phase that is mediated by Mrc1. The N-terminal phosphorylation of
      Mrc1 blocked replication and prevented transcription-associated recombination
      (TAR) and genomic instability during stress-induced gene expression in S phase.
      An unbiased kinome screening identified several kinases that phosphorylate Mrc1
      at the N terminus upon different environmental stresses. Mrc1 function was not
      restricted to environmental cues but was also required when unscheduled
      transcription was triggered by low fitness states such as genomic instability or
      slow growth. Our data indicate that Mrc1 integrates multiple signals, thereby
      defining a general safeguard mechanism to protect genomic integrity upon
      transcriptional outbursts.

PMID- 29371597
TI  - Immunological consequences of kidney cell death.
AB  - Death of renal cells is central to the pathophysiology of acute tubular necrosis,
      autoimmunity, necrotizing glomerulonephritis, cystic kidney disease, urosepsis,
      delayed graft function and transplant rejection. By means of regulated necrosis,
      immunogenic damage-associated molecular patterns (DAMPs) and highly reactive
      organelles such as lysosomes, peroxisomes and mitochondria are released from the
      dying cells, thereby causing an overwhelming immunologic response. The rupture of
      the plasma membrane exhibits the "point of no return" for the immunogenicity of
      regulated cell death, explaining why apoptosis, a highly organized cell death
      subroutine with long-lasting plasma membrane integrity, elicits hardly any immune
      response. Ferroptosis, an iron-dependent necrotic type cell death, results in the
      release of DAMPs and large amounts of lipid peroxides. In contrast, anti
      inflammatory cytokines are actively released from cells that die by necroptosis,
      limiting the DAMP-induced immune response to a surrounding microenvironment,
      whereas at the same time, inflammasome-associated caspases drive maturation of
      intracellularly expressed interleukin-1beta (IL-1beta). In a distinct setting,
      additionally interleukin-18 (IL-18) is expressed during pyroptosis, initiated by
      gasdermin-mediated plasma membrane rupture. As all of these pathways are
      druggable, we provide an overview of regulated necrosis in kidney diseases with a
      focus on immunogenicity and potential therapeutic interventions.

PMID- 29371598
TI  - Givinostat reduces adverse cardiac remodeling through regulating fibroblasts
      activation.
AB  - Cardiovascular diseases (CVDs) are a major burden on the healthcare system:
      indeed, over two million new cases are diagnosed every year worldwide.
      Unfortunately, important drawbacks for the treatment of these patients derive
      from our current inability to stop the structural alterations that lead to heart
      failure, the common endpoint of many CVDs. In this scenario, a better
      understanding of the role of epigenetics - hereditable changes of chromatin that
      do not alter the DNA sequence itself - is warranted. To date, hyperacetylation of
      histones has been reported in hypertension and myocardial infarction, but the use
      of inhibitors for treating CVDs remains limited. Here, we studied the effect of
      the histone deacetylase inhibitor Givinostat on a mouse model of acute myocardial
      infarction. We found that it contributes to decrease endothelial-to-mesenchymal
      transition and inflammation, reducing cardiac fibrosis and improving heart
      performance and protecting the blood vessels from apoptosis through the
      modulatory effect of cardiac fibroblasts on endothelial cells. Therefore,
      Givinostat may have potential for the treatment of CVDs.

PMID- 29371599
TI  - Cell death-based treatment of childhood cancer.
AB  - Any therapy that aims at eradicating a cancerous growth will have at its core a
      cell death-inducing component. Here we argue that paediatric oncology presents
      with its unique set of considerations and problems, which-while taking the lead
      from oncological research experiences obtained from the adult population-need to
      be clinically evaluated independently. This is particularly true when considering
      long-term side effects. Precision medicine offers a promising new approach in
      therapy, but given as a monotherapy and in a limited combination, as found in an
      apoptosis inducer/sensitiser combination, it will most likely lead to mutation
      escape of the target cell population and the emergence of resistance. However,
      using the increasing amount of the molecular data as the basis for a complex
      combination therapy combining several key components such as cell death-inducing
      agents, kinase inhibitors and BH3 mimetics, holds great promise.

PMID- 29371600
TI  - Cell death-based treatments of melanoma:conventional treatments and new
      therapeutic strategies.
AB  - The incidence of malignant melanoma has continued to rise during the past
      decades. However, in the last few years, treatment protocols have significantly
      been improved thanks to a better understanding of the key oncogenes and signaling
      pathways involved in its pathogenesis and progression. Anticancer therapy would
      either kill tumor cells by triggering apoptosis or permanently arrest them in the
      G1 phase of the cell cycle. Unfortunately, melanoma is often refractory to
      commonly used anticancer drugs. More recently, however, some new anticancer
      strategies have been developed that are "external" to cancer cells, for example
      stimulating the immune system's response or inhibiting angiogenesis. In fact, the
      increasing knowledge of melanoma pathogenetic mechanisms, in particular the
      discovery of genetic mutations activating specific oncogenes, stimulated the
      development of molecularly targeted therapies, a form of treatment in which a
      drug (chemical or biological) is developed with the goal of exclusively
      destroying cancer cells by interfering with specific molecules that drive growth
      and spreading of the tumor. Again, after the initial exciting results associated
      with targeted therapy, tumor resistance and/or relapse of the melanoma lesion
      have been observed. Hence, very recently, new therapeutic strategies based on the
      modulation of the immune system function have been developed. Since cancer cells
      are known to be capable of evading immune-mediated surveillance, i.e., to block
      the immune system cell activity, a series of molecular strategies, including
      monoclonal antibodies, have been developed in order to "release the brakes" on
      the immune system igniting immune reactivation and hindering metastatic melanoma
      cell growth. In this review we analyze the various biological strategies
      underlying conventional chemotherapy as well as the most recently developed
      targeted therapies and immunotherapies, pointing at the molecular mechanisms of
      cell injury and death engaged by the different classes of therapeutic agents.

PMID- 29371601
TI  - Streamlined asymmetric alpha-difunctionalization of ynones.
AB  - Ynones are a unique class of structural motifs that show remarkable chemical
      versatility. Chiral ynones, particularly those possessing an alpha-stereogenic
      center, are highly attractive templates for structural diversification. So far,
      only very limited examples have been reported for asymmetric alpha
      functionalization of ynones. Asymmetric double alpha-functionalization of ynones
      remains elusive. Here we describe a streamlined strategy for asymmetric alpha
      difunctionalization of ynones. We developed a gold-catalyzed multicomponent
      condensation reaction from a simple ynone, an amine, and an electrophilic
      alkynylating reagent to generate a 1,2-dialkynyl enamine, a key stable and
      isolable intermediate. This intermediate can undergo asymmetric fluorination
      catalyzed by a chiral phosphoric acid derivative. Chiral ynones with an alpha
      quaternary carbon and containing a fluorine and an alkyne can be synthesized in
      high yield and high ee. The synthetic utility of this method is demonstrated by
      the synthesis of enantioenriched tri(hetero)arylmethyl fluorides.

PMID- 29371603
TI  - Functional and structural damage of neurons by innate immune mechanisms during
      neurodegeneration.
AB  - Over the past decades, our view on neurodegenerative diseases has been mainly
      centered around neurons and their networks. Only recently it became evident that
      immunological processes arise alongside degenerating neurons, raising the
      question whether these represent just meaningless bystander reactions or in turn,
      contribute to pathogenesis and disease symptoms. When considering any effect of
      inflammatory events on the CNS one has to consider the site, duration and nature
      of immune activation. Likewise, one has to distinguish between mechanisms which
      directly impact the neuronal compartment and indirect mechanisms, which affect
      cells that are important for neuronal functioning and survival. As discussed in
      this review, both types of mechanisms may be present at the same time and
      additively or synergistically lead to neuronal demise. Inflammatory mediators
      released by the principle innate immune cells of the brain, microglia and
      astrocytes, can compromise the function and structure of neurons, thereby playing
      important roles in the pathogenesis of neurodegenerative diseases.

PMID- 29371602
TI  - AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation.
AB  - AMP-activated protein kinase (AMPK) has been shown to inhibit cardiac
      hypertrophy. Here, we show that submaximal AMPK activation blocks cardiomyocyte
      hypertrophy without affecting downstream targets previously suggested to be
      involved, such as p70 ribosomal S6 protein kinase, calcineurin/nuclear factor of
      activated T cells (NFAT) and extracellular signal-regulated kinases. Instead,
      cardiomyocyte hypertrophy is accompanied by increased protein O-GlcNAcylation,
      which is reversed by AMPK activation. Decreasing O-GlcNAcylation by inhibitors of
      the glutamine:fructose-6-phosphate aminotransferase (GFAT), blocks cardiomyocyte
      hypertrophy, mimicking AMPK activation. Conversely, O-GlcNAcylation-inducing
      agents counteract the anti-hypertrophic effect of AMPK. In vivo, AMPK activation
      prevents myocardial hypertrophy and the concomitant rise of O-GlcNAcylation in
      wild-type but not in AMPKalpha2-deficient mice. Treatment of wild-type mice with
      O-GlcNAcylation-inducing agents reverses AMPK action. Finally, we demonstrate
      that AMPK inhibits O-GlcNAcylation by mainly controlling GFAT phosphorylation,
      thereby reducing O-GlcNAcylation of proteins such as troponin T. We conclude that
      AMPK activation prevents cardiac hypertrophy predominantly by inhibiting O
      GlcNAcylation.

PMID- 29371605
TI  - Reemergence of high-Tc superconductivity in the (Li1-xFe x )OHFe1-ySe under high
      pressure.
AB  - In order to elucidate pressure-induced second superconducting phase (SC-II) in A
      x Fe2-ySe2 (A = K, Rb, Cs, and Tl) having an intrinsic phase separation, we
      perform a detailed high-pressure magnetotransport study on the isoelectronic,
      phase-pure (Li1-xFe x )OHFe1-ySe single crystals. Here we show that its ambient
      pressure superconducting phase (SC-I) with a critical temperature Tc ~ 40 K is
      suppressed gradually to below 2 K and an SC-II phase emerges above Pc ~ 5 GPa
      with Tc increasing progressively to above 50 K up to 12.5 GPa. Our high-precision
      resistivity data uncover a sharp transition of the normal state from Fermi liquid
      for SC-I to non-Fermi liquid for SC-II phase. In addition, the reemergence of
      high-Tc SC-II is found to accompany with a concurrent enhancement of electron
      carrier density. Without structural transition below 10 GPa, the observed SC-II
      with enhanced carrier density should be ascribed to an electronic origin
      presumably associated with pressure-induced Fermi surface reconstruction.

PMID- 29371604
TI  - SWELL1 is a glucose sensor regulating beta-cell excitability and systemic
      glycaemia.
AB  - Insulin secretion is initiated by activation of voltage-gated Ca2+ channels
      (VGCC) to trigger Ca2+-mediated insulin vesicle fusion with the beta-cell plasma
      membrane. The firing of VGCC requires beta-cell membrane depolarization, which is
      regulated by a balance of depolarizing and hyperpolarizing ionic currents. Here,
      we show that SWELL1 mediates a swell-activated, depolarizing chloride current
      (ICl,SWELL) in both murine and human beta-cells. Hypotonic and glucose-stimulated
      beta-cell swelling activates SWELL1-mediated ICl,SWELL and this contributes to
      membrane depolarization and activation of VGCC-dependent intracellular calcium
      signaling. SWELL1 depletion in MIN6 cells and islets significantly impairs
      glucose-stimulated insulin secretion. Tamoxifen-inducible beta-cell-targeted
      Swell1 KO mice have normal fasting serum glucose and insulin levels but impaired
      glucose-stimulated insulin secretion and glucose tolerance; and this is further
      exacerbated in mild obesity. Our results reveal that beta-cell SWELL1 modulates
      insulin secretion and systemic glycaemia by linking glucose-mediated beta-cell
      swelling to membrane depolarization and activation of VGCC-triggered calcium
      signaling.

PMID- 29371606
TI  - Assessment of suitable reference genes for RT-qPCR studies in chronic
      rhinosinusitis.
AB  - Reverse transcription-quantitative polymerase chain reaction is a valuable and
      reliable method for gene quantification. Target gene expression is usually
      quantified by normalization using reference genes (RGs), and accurate
      normalization is critical for producing reliable data. However, stable RGs in
      nasal polyps and sinonasal tissues from patients with chronic rhinosinusitis
      (CRS) have not been well investigated. Here, we used a two-stage study design to
      identify stable RGs. We assessed the stability of 15 commonly used candidate RGs
      using five programs-geNorm, NormFinder, BestKeeper, DeltaCT, and RefFinder.
      Ribosomal protein lateral stalk subunit P1 (RPLP1) and ribosomal protein lateral
      stalk subunit P0 (RPLP0) were the two most stable RGs in the first stage of the
      study, and these results were validated in the second stage. The commonly used
      RGs beta-actin (ACTB) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were
      unstable according to all of the algorithms used. The findings were further
      validated via relative quantification of IL-5, CCL11, IFN-gamma, and IL-17A using
      the stable and unstable RGs. The relative expression levels varied greatly
      according to normalization with the selected RGs. Appropriate selection of stable
      RGs will allow more accurate determination of target gene expression levels in
      patients with CRS.

PMID- 29371607
TI  - Degradation routes of trafficking-defective VLDLR mutants associated with
      Dysequilibrium syndrome.
AB  - Low density lipoprotein receptor (LDLR) family members are involved in signaling
      in the developing brain. Previously we have reported that missense mutations in
      the Very Low Density Lipoprotein Receptor gene (VLDLR), causing Dysequilibrium
      syndrome (DES), disrupt ligand-binding, due to endoplasmic reticulum (ER)
      retention of the mutants. We explored the degradation routes of these VLDLR
      mutants in cultured cells. Our results indicate that VLDLR mutants are retained
      in the ER for prolonged periods which could be facilitated by association with
      the ER-resident chaperone calnexin. The mutants were prone to aggregation and
      capable of eliciting ER stress. The VLDLR mutants were found to be degraded
      predominantly by the proteasomal pathway, since ubiquitinated VLDLR was found to
      accumulate in response to proteasomal inhibition. Further, the mutants were found
      to interact with the ER degradation adaptor protein SEL1L. The degradation of
      VLDLR wild type and mutant were delayed in CRISPR/Cas9 edited SEL1L knock-out
      cells which was reversed by exogenous expression of SEL1L. In summary, ER
      retention of pathogenic VLDLR mutants involves binding to calnexin, elevated ER
      stress, and delayed degradation which is dependent on SEL1L. Since core LDLR
      family members share common structural domains, common mechanisms may be involved
      in their ER processing.

PMID- 29371608
TI  - Abnormal grain growth mediated by fractal boundary migration at the nanoscale.
AB  - Modern engineered materials are composed of space-filling grains or domains
      separated by a network of interfaces or boundaries. Such polycrystalline
      microstructures have the capacity to coarsen through boundary migration. Grain
      growth theories account for the topology of grains and the connectivity of the
      boundary network in terms of the familiar Euclidian dimension and Euler's
      polyhedral formula, both of which are based on integer numbers. However, we
      recently discovered an unusual growth mode in a nanocrystalline Pd-Au alloy, in
      which grains develop complex, highly convoluted surface morphologies that are
      best described by a fractional dimension of ~1.2 (extracted from the perimeters
      of grain cross sections). This fractal value is characteristic of a variety of
      domain growth scenarios-including explosive percolation, watersheds of random
      landscapes, and the migration of domain walls in a random field of pinning
      centers-which suggests that fractal grain boundary migration could be a
      manifestation of the same universal behavior.

PMID- 29371609
TI  - Luminance gradient at object borders communicates object location to the human
      oculomotor system.
AB  - The locations of objects in our environment constitute arguably the most
      important piece of information our visual system must convey to facilitate
      successful visually guided behaviour. However, the relevant objects are usually
      not point-like and do not have one unique location attribute. Relatively little
      is known about how the visual system represents the location of such large
      objects as visual processing is, both on neural and perceptual level, highly edge
      dominated. In this study, human observers made saccades to the centres of
      luminance defined squares (width 4 deg), which appeared at random locations (8
      deg eccentricity). The phase structure of the square was manipulated such that
      the points of maximum luminance gradient at the square's edges shifted from trial
      to trial. The average saccade endpoints of all subjects followed those shifts in
      remarkable quantitative agreement. Further experiments showed that the shifts
      were caused by the edge manipulations, not by changes in luminance structure near
      the centre of the square or outside the square. We conclude that the human visual
      system programs saccades to large luminance defined square objects based on edge
      locations derived from the points of maximum luminance gradients at the square's
      edges.

PMID- 29371610
TI  - Starfish Apaf-1 activates effector caspase-3/9 upon apoptosis of aged eggs.
AB  - Caspase-3-related DEVDase activity is initiated upon apoptosis in unfertilized
      starfish eggs. In this study, we cloned a starfish procaspase-3 corresponding to
      mammalian effector caspase containing a CARD that is similar to the amino
      terminal CARD of mammalian capsase-9, and we named it procaspase-3/9. Recombinant
      procaspase-3/9 expressed at 15  degrees C was cleaved to form active caspase-3/9
      which has DEVDase activity. Microinjection of the active caspase-3/9 into
      starfish oocytes/eggs induced apoptosis. An antibody against the recombinant
      protein recognized endogenous procaspase-3/9 in starfish oocytes, which was
      cleaved upon apoptosis in aged unfertilized eggs. These results indicate that
      caspase-3/9 is an effector caspase in starfish. To verify the mechanism of
      caspase-3/9 activation, we cloned starfish Apaf-1 containing a CARD, a NOD, and
      11 WD40 repeat regions, and we named it sfApaf-1. Recombinant sfApaf-1 CARD
      interacts with recombinant caspase-3/9 CARD and with endogenous procaspase-3/9 in
      cell-free preparations made from starfish oocytes, causing the formation of
      active caspase-3/9. When the cell-free preparation without mitochondria was
      incubated with inactive recombinant procaspase-3/9 expressed at 37  degrees C,
      DEVDase activity increased and apoptosome-like complexes were formed in the high
      molecular weight fractions containing both sfApaf-1 and cleaved caspase-3/9.
      These results suggest that sfApaf-1 activation is not dependent on cytochrome c.

PMID- 29371611
TI  - Enhanced Skin Permeation of Anti-wrinkle Peptides via Molecular Modification.
AB  - Wrinkles can have a negative effect on quality of life and Botox is one of the
      most effective and common treatments. Argireline (Arg0), a mimetic of Botox, has
      been found to be safer than Botox and effective in reducing wrinkles, with
      efficacies up to 48% upon 4 weeks of twice daily treatment. However, the skin
      permeation of Arg0 is poor, due to its large molecular weight and hydrophilicity.
      Arg0 exists in zwitterionic form and this charged state hindered its skin
      permeation. Chemical modification of the peptide structure to reduce the
      formation of zwitterions may result in increased skin permeability. We
      investigated a total of 4 peptide analogues (Arg0, Arg1, Arg2, Arg3), in terms of
      skin permeation and wrinkle reduction. The 4 peptides were dissolved in various
      propylene glycol and water co-solvents. Enhanced human skin permeation was
      demonstrated by both Arg2 and Arg3 in vitro. On the other hand, the abilities of
      the 4 analogues to reduce wrinkle formation were also compared using primary
      human dental pulp stem cells derived neurons. By measuring the inhibition of
      glutamate release from the neurons in vitro, it was shown that Arg3 was the most
      effective, followed by Arg1, Arg0 and Arg2.

PMID- 29371612
TI  - SlMYB12 Regulates Flavonol Synthesis in Three Different Cherry Tomato Varieties.
AB  - Cherry tomato (Lycopersicon esculentum M.) is considered a healthy fruit
      worldwide due to its wide range of nutrients. Flavonol, one of the major
      nutrients in cherry tomato, has antioxidant and cell-modulating properties. In
      this study, we showed a correlation between the expression of SlMYB12 and
      flavonol content (R2 = 0.922). To characterize the function of SlMYB12, SlMYB12
      overexpressing transgenic tomato plants were generated in three different cherry
      tomato varieties. Significant increases in flavonol content and flavonol
      biosynthetic gene expression were identified in SlMYB12-overexpressing plants.
      Therefore, we suggest that SlMYB12 plays a positive role in the flavonol
      biosynthesis pathway in cherry tomatoes, which further indicates a potential role
      as a marker in analyzing flavonol content in different cherry tomato varieties.

PMID- 29371614
TI  - Biosensing with the singular phase of an ultrathin metal-dielectric nanophotonic
      cavity.
AB  - The concept of point of darkness has received much attention for biosensing based
      on phase-sensitive detection and perfect absorption of light. The maximum phase
      change is possible at the point of darkness where the reflection is almost zero.
      To date, this has been experimentally realized using different material systems
      through the concept of topological darkness. However, complex nanopatterning
      techniques are required to realize topological darkness. Here, we report an
      approach to realize perfect absorption and extreme phase singularity using a
      simple metal-dielectric multilayer thin-film stack. The multilayer stack works on
      the principle of an asymmetric Fabry-Perot cavity and shows an abrupt phase
      change at the reflectionless point due to the presence of a highly absorbing
      ultrathin film of germanium in the stack. In the proof-of-concept phase-sensitive
      biosensing experiments, we functionalize the film surface with an ultrathin layer
      of biotin-thiol to capture streptavidin at a low concentration of 1 pM.

PMID- 29371613
TI  - The MDM2-p53 pathway is involved in preconditioning-induced neuronal tolerance to
      ischemia.
AB  - Brain preconditioning (PC) refers to a state of transient tolerance against a
      lethal insult that can be evoked by a prior mild event. It is thought that PC may
      induce different pathways responsible for neuroprotection, which may involve the
      attenuation of cell damage pathways, including the apoptotic cell death. In this
      context, p53 is a stress sensor that accumulates during brain ischemia leading to
      neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3
      ubiquitin ligase, is the main cellular antagonist of p53, mediating its
      degradation by the proteasome. Here, we study the role of MDM2-p53 pathway on PC
      induced neuroprotection both in cultured neurons (in vitro) and rat brain (in
      vivo). Our results show that PC increased neuronal MDM2 protein levels, which
      prevented ischemia-induced p53 stabilization and neuronal death. Indeed, PC
      attenuated ischemia-induced activation of the p53/PUMA/caspase-3 signaling
      pathway. Pharmacological inhibition of MDM2-p53 interaction in neurons abrogated
      PC-induced neuroprotection against ischemia. Finally, the relevance of the MDM2
      p53 pathway was confirmed in rat brain using a PC model in vivo. These findings
      demonstrate the key role of the MDM2-p53 pathway in PC-induced neuroprotection
      against a subsequent ischemic insult and poses MDM2 as an essential target in
      ischemic tolerance.

PMID- 29371615
TI  - Retinoic acid prevents immunogenicity of milk lipocalin Bos d 5 through binding
      to its immunodominant T-cell epitope.
AB  - The major cow's milk allergen Bos d 5 belongs to the lipocalin protein family,
      with an intramolecular pocket for hydrophobic ligands. We investigated whether
      Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA),
      would elicit differential immune responses compared to the unloaded state. By in
      silico docking an affinity energy of -7.8 kcal/mol was calculated for RA into Bos
      d 5. Loading of RA to Bos d 5 could be achieved in vitro, as demonstrated by ANS
      displacement assay, but had no effect on serum IgE binding in tolerant or
      challenge-positive milk allergic children. Bioinformatic analysis revealed that
      RA binds to the immunodominant T-cell epitope region of Bos d 5. In accordance,
      Bos d 5 significantly suppressed the CD3+ CD4+ cell numbers, proliferative
      response and IL-10, IL-13 and IFN-gamma secretion from stimulated human PBMCs
      only when complexed with RA. This phenomenon was neither associated with
      apoptosis of T-cells nor with the activation of Foxp3+ T-cells, but correlated
      likely with enhanced stability to lysosomal digestion due to a predicted overlap
      of Cathepsin S cleavage sites with the RA binding site. Taken together, proper
      loading of Bos d 5 with RA may suppress its immunogenicity and prevent its
      allergenicity.

PMID- 29371616
TI  - Necroptosis and neutrophil-associated disorders.
AB  - Necroptosis is a form of regulated necrosis and is dependent on a signaling
      pathway involving receptor interacting protein kinase-3 (RIPK3) and mixed lineage
      kinase domain-like protein (MLKL). Necroptosis is considered to have important
      functions in inflammation and, based on studies with animal disease models, is
      believed likely to be involved in the pathogenesis of many human inflammatory
      diseases. In neutrophils, necroptosis has recently been reported to be triggered
      by tumor necrosis factor (TNF) stimulation, ligation of adhesion receptors,
      exposure to monosodium urate (MSU) crystals, or phagocytosis of Staphylococcus
      aureus (S. aureus). Because neutrophils are involved in many kinds of tissue
      inflammation and disease, neutrophil necroptosis probably plays a vital role in
      such processes. Dissecting the signaling pathway of neutrophil necroptotic death
      may help to identify novel drug targets for inflammatory or autoimmune diseases.
      In this review, we discuss different mechanisms which regulate neutrophil
      necroptosis and are thus potentially important in neutrophil-associated
      disorders.

PMID- 29371618
TI  - Decentralized dynamic understanding of hidden relations in complex networks.
AB  - Almost all the natural or human made systems can be understood and controlled
      using complex networks. This is a difficult problem due to the very large number
      of elements in such networks, on the order of billions and higher, which makes it
      impossible to use conventional network analysis methods. Herein, we employ
      artificial intelligence (specifically swarm computing), to compute centrality
      metrics in a completely decentralized fashion. More exactly, we show that by
      overlaying a homogeneous artificial system (inspired by swarm intelligence) over
      a complex network (which is a heterogeneous system), and playing a game in the
      fused system, the changes in the homogeneous system will reflect perfectly the
      complex network properties. Our method, dubbed Game of Thieves (GOT), computes
      the importance of all network elements (both nodes and edges) in polylogarithmic
      time with respect to the total number of nodes. Contrary, the state-of-the-art
      methods need at least a quadratic time. Moreover, the excellent capabilities of
      our proposed approach, it terms of speed, accuracy, and functionality, open the
      path for better ways of understanding and controlling complex networks.

PMID- 29371617
TI  - Risks, Release and Concentrations of Engineered Nanomaterial in the Environment.
AB  - For frequently used engineered nanomaterials (ENMs) CeO2-, SiO2-, and Ag, past,
      current, and future use and environmental release are investigated. Considering
      an extended period (1950 to 2050), we assess ENMs released through commercial
      activity as well as found in natural and technical settings. Temporal dynamics,
      including shifts in release due to ENM product application, stock (delayed use),
      and subsequent end-of-life product treatment were taken into account. We
      distinguish predicted concentrations originating in ENM use phase and those
      originating from end-of-life release. Furthermore, we compare Ag- and CeO2-ENM
      predictions with existing measurements. The correlations and limitations of the
      model, and the analytic validity of our approach are discussed in the context of
      massive use of assumptive model data and high uncertainty on the colloidal
      material captured by the measurements. Predictions for freshwater CeO2-ENMs range
      from 1 pg/l (2017) to a few hundred ng/l (2050). Relative to CeO2, the SiO2-ENMs
      estimates are approximately 1,000 times higher, and those for Ag-ENMs 10 times
      lower. For most environmental compartments, ENM pose relatively low risk;
      however, organisms residing near ENM 'point sources' (e.g., production plant
      outfalls and waste treatment plants), which are not considered in the present
      work, may be at increased risk.

PMID- 29371619
TI  - Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces
      Potent Transmission-Blocking Activity.
AB  - An anti-malarial transmission blocking vaccine (TBV) would be an important tool
      for disease control or elimination, though current candidates have failed to
      induce high efficacy in clinical studies. The ookinete surface protein P25 is a
      primary target for TBV development, but heterologous expression of P25 with
      appropriate conformation is problematic and a pre-requisite for achieving
      functional titers. A potential alternative to recombinant/sub-unit vaccine is
      immunization with a non-pathogenic, whole-parasite vaccine. This study examines
      the ability of a purified transgenic rodent-malaria parasite (PbPfs25DR3),
      expressing Plasmodium falciparum P25 in native conformation on the P. berghei
      ookinete surface, to act as a TBV. Vaccination with purified PbPfs25DR3 ookinetes
      produces a potent anti-Pfs25 response and high transmission-blocking efficacy in
      the laboratory, findings that are then translated to experimentation on natural
      field isolates of P. falciparum from infected individuals in Burkina Faso.
      Efficacy is demonstrated in the lab and the field (up to 93.3%/97.1% reductions
      in transmission intensity respectively), with both a homologous strategy with one
      and two boosts, and as part of a prime-boost regime, providing support for the
      future development of a whole-parasite TBV.

PMID- 29371622
TI  - On the origins of strain inhomogeneity in amorphous materials.
AB  - Strain is a crucial measure of materials deformation for evaluating and
      predicting the mechanical response, strength, and fracture. The spatial
      resolution attainable by the modern real and reciprocal space techniques
      continues to improve, alongside the ability to carry out atomistic simulations.
      This is offering new insights into the very concept of strain. In crystalline
      materials, the presence of well-defined, stable atomic planes allows defining
      strain as the relative change in the interplanar spacing. However, the presence
      of disorder, e.g. locally around defects such as dislocation cores, and
      particularly the pervasive atomic disorder in amorphous materials challenge
      existing paradigms: disorder prevents a reference configuration being defined,
      and allows strain to be accommodated in a different manner to crystalline
      materials. As an illustration, using experimental pair distribution function
      analysis in combination with Molecular Dynamic (MD) simulations, we highlight the
      importance of bond angle change vs bond stretching for strain accommodation in
      amorphous systems.

PMID- 29371621
TI  - Molecular Mechanism of Resveratrol's Lipid Membrane Protection.
AB  - Resveratrol, a natural compound found in red wine and various vegetables, has
      drawn increasing interest due to its reported benefit in cardiovascular
      protection, neurodegenerative disorders, and cancer therapy. The mechanism by
      which resveratrol exerts such pleiotropic effects remains unclear. It remains as
      one of the most discussed polyphenol compounds in the debating "French Paradox".
      In this study, using molecular dynamics simulations of dipalmitoyl
      phosphatidylcholine (DPPC) bilayer with resveratrol, we generated a free energy
      map of resveratrol's location and orientation of inside the lipid bilayer. We
      found that resveratrol increases the surface area per lipid and decreases
      membrane thickness, which is the opposite effect of the well-studied cholesterol
      on liquid phase DPPC. Most importantly, based on the simulation observation that
      resveratrol has a high probability of forming hydrogen bonds with sn-1 and sn-2
      ester groups, we discovered a new mechanism using experimental approach, in which
      resveratrol protects both sn-1 and sn-2 ester bonds of DPPC and distearoyl
      phosphatidylcholine (DSPC) from phospholipase A1 (PLA1) and phospholipase A2
      (PLA2) cleavage. Our study elucidates the new molecular mechanism of potential
      health benefits of resveratrol and possibly other similar polyphenols and
      provides a new paradigm for drug design based on resveratrol and its analogs.

PMID- 29371620
TI  - Nanoparticle Properties Modulate Their Attachment and Effect on Carrier Red Blood
      Cells.
AB  - Attachment of nanoparticles (NPs) to the surface of carrier red blood cells
      (RBCs) profoundly alters their interactions with the host organism, decelerating
      NP clearance from the bloodstream while enabling NP transfer from the RBC surface
      to the vascular cells. These changes in pharmacokinetics of NPs imposed by
      carrier RBCs are favorable for many drug delivery purposes. On the other hand,
      understanding effects of NPs on the carrier RBCs is vital for successful
      translation of this novel drug delivery paradigm. Here, using two types of
      distinct nanoparticles (polystyrene (PSNP) and lysozyme-dextran nanogels (LDNG))
      we assessed potential adverse and sensitizing effects of surface adsorption of
      NPs on mouse and human RBCs. At similar NP loadings (approx. 50 particles per
      RBC), adsorption of PSNPs, but not LDNGs, induces RBCs agglutination and
      sensitizes RBCs to damage by osmotic, mechanical and oxidative stress. PSNPs, but
      not LDNGs, increase RBC stiffening and surface exposure of phosphatidylserine,
      both known to accelerate RBC clearance in vivo. Therefore, NP properties and
      loading amounts have a profound impact on RBCs. Furthermore, LDNGs appear
      conducive to nanoparticle drug delivery using carrier RBCs.

PMID- 29371623
TI  - Pervasive Rise of Small-scale Deforestation in Amazonia.
AB  - Understanding forest loss patterns in Amazonia, the Earth's largest rainforest
      region, is critical for effective forest conservation and management. Following
      the most detailed analysis to date, spanning the entire Amazon and extending over
      a 14-year period (2001-2014), we reveal significant shifts in deforestation
      dynamics of Amazonian forests. Firstly, hotspots of Amazonian forest loss are
      moving away from the southern Brazilian Amazon to Peru and Bolivia. Secondly,
      while the number of new large forest clearings (>50 ha) has declined
      significantly over time (46%), the number of new small clearings (<1 ha)
      increased by 34% between 2001-2007 and 2008-2014. Thirdly, we find that small
      scale low-density forest loss expanded markedly in geographical extent during
      2008-2014. This shift presents an important and alarming new challenge for forest
      conservation, despite reductions in overall deforestation rates.

PMID- 29371624
TI  - The ecological origins of snakes as revealed by skull evolution.
AB  - The ecological origin of snakes remains amongst the most controversial topics in
      evolution, with three competing hypotheses: fossorial; marine; or terrestrial.
      Here we use a geometric morphometric approach integrating ecological,
      phylogenetic, paleontological, and developmental data for building models of
      skull shape and size evolution and developmental rate changes in squamates. Our
      large-scale data reveal that whereas the most recent common ancestor of crown
      snakes had a small skull with a shape undeniably adapted for fossoriality, all
      snakes plus their sister group derive from a surface-terrestrial form with non
      fossorial behavior, thus redirecting the debate toward an underexplored
      evolutionary scenario. Our comprehensive heterochrony analyses further indicate
      that snakes later evolved novel craniofacial specializations through global
      acceleration of skull development. These results highlight the importance of the
      interplay between natural selection and developmental processes in snake origin
      and diversification, leading first to invasion of a new habitat and then to
      subsequent ecological radiations.

PMID- 29371625
TI  - Structural effect of two-dimensional BNNS on grain growth suppressing behaviors
      in Al-matrix nanocomposites.
AB  - While nanocrystalline (NC) metals exhibit superior strength to conventional
      microcrystalline metals, their thermal instability has hampered their application
      at high temperatures. Herein, two-dimensional (2D) boron nitride nanosheets
      (BNNS) are proposed as reinforcement to enhance the strength as well as the
      thermal stability of NC Al. The strength of pure Al was increased from 80 to 468
      MPa by refining its grains from ~600 to ~40 nm, and it was further enhanced to
      685 MPa by incorporating 2 vol% of BNNS. Moreover, the small amount of BNNS was
      found to effectively suppress grain growth of NC Al at 580  degrees C (~0.9 Tm,
      where Tm is the melting point of Al), which prevented a strength drop at high
      temperature. Finally, the Zener pinning model in conjunction with phase-field
      simulations was utilized to qualitatively analyze the effect of the BNNS on the
      grain boundary pinning as a function of volume, shape, and orientation of the
      reinforcement. The model demonstrated that the pinning force of 2D reinforcements
      is much higher than that of spherical particles. Hence, 2D BNNS offer the
      possibility of developing Al-matrix nanocomposites for high-temperature
      structural applications.

PMID- 29371627
TI  - Volume, size, professionals' specialization and nutrition management of NICUs and
      their association with treatment quality in VLBW infants.
AB  - OBJECTIVE: To assess the association of volume, size, the availability of highly
      specialized professionals and nutrition management of NICUs with treatment
      quality among VLBW infants. STUDY DESIGN: A prospective multicenter study of 923
      VLBW infants in 66 German NICUs, born between May and October 2013. Using
      multilevel modeling, we examined the association between the aforementioned
      organizational characteristics and treatment quality, measured via major
      morbidities (severe IVH, PVL, BPD, NEC, FIP, ROP, and discharge without severe
      complications) and medical process measures of VLBW infants. RESULTS: After risk
      adjustment and accounting for other NICU characteristics, infants in low-volume
      NICUs were at higher risk of IVH, ROP and PVL. However, the initial effect of
      volume on process measures (growth velocity, administration of antenatal
      steroids) disappeared. CONCLUSION: Volume can only partially explain differences
      in the treatment quality of VLBWs. The underlying organizational mechanisms
      should be considered to improve the quality of care.

PMID- 29371628
TI  - Impact of NICU admission on Colorado-born late preterm infants: breastfeeding
      initiation, continuation and in-hospital breastfeeding practices.
AB  - OBJECTIVE: Compare breastfeeding initiation and continuation rates, and in
      hospital breastfeeding practices, of late preterm infants (LPIs) cared for in a
      NICU versus those cared for exclusively in the nursery (non-NICU). STUDY DESIGN:
      Using data from the 2009-2014 Colorado Pregnancy Risk Assessment Monitoring
      System (PRAMS), breastfeeding initiation, continuation, and in-hospital
      breastfeeding practices of NICU versus non-NICU LPIs (34 0/7 to 36 6/7 weeks
      gestation, n = 20,767) were analyzed, and multivariate models were created
      controlling for maternal and infant characteristics. RESULTS: Mothers of NICU
      LPIs were equally likely to initiate breastfeeding (APR 1.0; 95% CI 0.95-1.06)
      but less likely to continue breastfeeding at 10 weeks (APR 0.86; 95% CI 0.76
      0.99) compared to mothers of non-NICU LPIs. Mothers of NICU LPIs were less likely
      to breastfeed in the hospital, less likely to be told to feed infants on demand,
      and more likely to be given a breast pump during hospitalization. CONCLUSIONS:
      There are significant differences in both breastfeeding continuation and several
      in-hospital breastfeeding practices for NICU versus non-NICU LPIs. Further
      research is needed so that targeted policies and programs can be developed to
      improve breastfeeding rates in this vulnerable population.

PMID- 29371626
TI  - A global ocean atlas of eukaryotic genes.
AB  - While our knowledge about the roles of microbes and viruses in the ocean has
      increased tremendously due to recent advances in genomics and metagenomics,
      research on marine microbial eukaryotes and zooplankton has benefited much less
      from these new technologies because of their larger genomes, their enormous
      diversity, and largely unexplored physiologies. Here, we use a
      metatranscriptomics approach to capture expressed genes in open ocean Tara Oceans
      stations across four organismal size fractions. The individual sequence reads
      cluster into 116 million unigenes representing the largest reference collection
      of eukaryotic transcripts from any single biome. The catalog is used to unveil
      functions expressed by eukaryotic marine plankton, and to assess their functional
      biogeography. Almost half of the sequences have no similarity with known
      proteins, and a great number belong to new gene families with a restricted
      distribution in the ocean. Overall, the resource provides the foundations for
      exploring the roles of marine eukaryotes in ocean ecology and biogeochemistry.

PMID- 29371629
TI  - Alterations of oral microbiota distinguish children with autism spectrum
      disorders from healthy controls.
AB  - Altered gut microbiota is associated with autism spectrum disorders (ASD), a
      group of complex, fast growing but difficult-to-diagnose neurodevelopmental
      disorders worldwide. However, the role of the oral microbiota in ASD remains
      unexplored. Via high-throughput sequencing of 111 oral samples in 32 children
      with ASD and 27 healthy controls, we demonstrated that the salivary and dental
      microbiota of ASD patients were highly distinct from those of healthy
      individuals. Lower bacterial diversity was observed in ASD children compared to
      controls, especially in dental samples. Also, principal coordinate analysis
      revealed divergences between ASD patients and controls. Moreover, pathogens such
      as Haemophilus in saliva and Streptococcus in plaques showed significantly higher
      abundance in ASD patients, whereas commensals such as Prevotella, Selenomonas,
      Actinomyces, Porphyromonas, and Fusobacterium were reduced. Specifically, an
      overt depletion of Prevotellaceae co-occurrence network in ASD patients was
      obtained in dental plaques. The distinguishable bacteria were also correlated
      with clinical indices, reflecting disease severity and the oral health status
      (i.e. dental caries). Finally, diagnostic models based on key microbes were
      constructed, with 96.3% accuracy in saliva. Taken together, this study
      characterized the habitat-specific profile of the oral microbiota in ASD
      patients, which might help develop novel strategies for the diagnosis of ASD.

PMID- 29371630
TI  - Necessity of p53-binding to the CDH1 locus for its expression defines two
      epithelial cell types differing in their integrity.
AB  - TP53 mutation (i.e., loss of normal-p53) may evoke epithelial-mesenchymal
      transition (EMT), which was previously attributed to loss of certain miRNAs.
      However, not all epithelial cells undergo EMT upon TP53 mutation, and the p53
      miRNA axis may not fully explain p53 function in epithelial integrity. We here
      show two modes of epithelial integrity: one involves p53-binding to a nucleotide
      region and the other does not. In the former, p53 binds to the CDH1 (encoding E
      cadherin) locus to antagonize EZH2-mediated H3K27 trimethylation (H3K27me3) to
      maintain high levels of acetylation of H3K27 (H3K27ac). In the latter, the same
      locus is not highly acetylated at H3K27, and does not allow p53-binding, nor
      needs to antagonize EZH2. We moreover demonstrated that although the CDH1 locus
      in the p53-independent cells, but not in fibroblasts, becomes high-H3K27ac by
      butyrate and allows p53-biniding, their CDH1 expression does not become dependent
      on p53. Our results identified novel modes of the epithelial integrity, in which
      the same epithelial-specific gene locus exhibits different requirement for p53
      with different histone modifications among different epithelial cells to warrant
      its expression.

PMID- 29371631
TI  - A Strategy for Nonmigrating Plasticized PVC Modified with Mannich base of Waste
      Cooking Oil Methyl Ester.
AB  - The waste cooking oil (WCO) production from the catering industry and food
      processing industry causes serious environmental, economic and social problems.
      However, WCO can be used for the preparation of fine chemicals such as internal
      plasticizer. With this aim, this work is focused on preparing internal
      plasticizer by using WCO and determining technical viability of non-migration
      poly (vinyl chloride) (PVC) materials. The mannich base of waste cooking oil
      methyl ester (WCOME) was synthesized from WCO via esterification,
      interesterification and mannich reaction, which was used to produce self
      plasticization PVC materials as an internal plasticizer. The results showed that
      the PVC was plasticized effectively. Self-plasticization PVC films showed no
      migration in n-hexane, but 15.7% of dioctyl phthalate (DOP) leached from
      DOP/PVC(50/50) system into n-hexane. These findings transformed the traditional
      plastic processing technology and obtained cleaner production of no migration
      plasticizer from WCO.

PMID- 29371632
TI  - Distribution and accumulation of dietary ergothioneine and its metabolites in
      mouse tissues.
AB  - L-ergothioneine (ET) is a diet-derived amino acid that accumulates at high
      concentrations in animals and humans. Numerous studies have highlighted its
      antioxidant abilities in vitro, and possible cytoprotective capabilities in vivo.
      We investigated the uptake and distribution of ET in various organs by a highly
      sensitive and specific liquid chromatography coupled tandem mass spectrometry (LC
      MS/MS) technique, both before and after oral administration of pure ET (35 and 70
      mg/kg/day for 1, 7, and 28 days) to male C57BL6J mice. ET primarily concentrates
      in the liver and whole blood, and also in spleen, kidney, lung, heart,
      intestines, eye, and brain tissues. Strong correlations were found between ET and
      its putative metabolites - hercynine, ET-sulfonate (ET-SO3H), and S-methyl ET.
      Hercynine accumulates in the brain after prolonged ET administration. This study
      demonstrates the uptake and distribution of ET and provides a foundation for
      future studies with ET to target oxidative damage in a range of tissues in human
      diseases.

PMID- 29371633
TI  - Contrasting temperature trends across the ice-free part of Greenland.
AB  - Temperature changes in the Arctic have notable impacts on ecosystem structure and
      functioning, on soil carbon dynamics, and on the stability of permafrost, thus
      affecting ecosystem functions and putting man-built infrastructure at risk.
      Future warming in the Arctic could accelerate important feedbacks in permafrost
      degradation processes. Therefore it is important to map vulnerable areas most
      likely to be impacted by temperature changes and at higher risk of degradation,
      particularly near communities, to assist adaptation to climate change. Currently,
      these areas are poorly assessed, especially in Greenland. Here we quantify trends
      in satellite-derived land surface temperatures and modelled air temperatures,
      validated against observations, across the entire ice-free Greenland. Focus is on
      the past 30 years, to characterize significant changes and potentially vulnerable
      regions at a 1 km resolution. We show that recent temperature trends in Greenland
      vary significantly between seasons and regions and that data with resolutions
      down to single km2 are critical to map temperature changes for guidance of
      further local studies and decision-making. Only a fraction of the ice-free
      Greenland seems vulnerable due to warming when analyzing year 2001-2015, but the
      most pronounced changes are found in the most populated parts of Greenland. As
      Greenland represents important gradients of north/south coast/inland/distance to
      large ice sheets, the conclusions are also relevant in an upscaling to greater
      Arctic areas.

PMID- 29371634
TI  - Urban environment predisposes dogs and their owners to allergic symptoms.
AB  - Our companion-animals, dogs, suffer increasingly from non-communicable diseases,
      analogous to those common in humans, such as allergic manifestations. In humans,
      living in rural environments is associated with lower risk of allergic diseases.
      Our aim was to explore whether a similar pattern can be found in dogs, using a
      nation-wide survey in Finland (n = 5722). We characterised the land-use around
      dog's home at the time of birth as well as around its current home, and described
      several lifestyle factors. The severity of owner-reported allergic symptoms in
      dogs was estimated with a comprehensive set of questions, developed by experts of
      canine dermatology. Also, the prevalence of diagnosed allergies in dog owners was
      recorded. The results indicate that allergic symptoms are more prevalent in urban
      environments both in dog owners and in dogs (accounting the effect of dog breed).
      Several factors related to rural living, such as bigger family size and regular
      contact with farm animals and other pets, were also protective against allergic
      symptoms in dogs. Interestingly, allergic dogs were more likely to have allergic
      owners than healthy dogs were. Therefore, we suggest that the mutual presence of
      allergic symptoms in both species indicates common underlying causal factors of
      allergic diseases.

PMID- 29371635
TI  - Global Quantitative Proteomics reveal Deregulation of Cytoskeletal and Apoptotic
      Signalling Proteins in Oral Tongue Squamous Cell Carcinoma.
AB  - Oral malignancies remain to have higher morbidity and mortality rates owing to
      the poor understanding of the carcinogenesis and the lack of early detection and
      diagnosis. The lack of established biomarkers for oral tongue squamous cell
      carcinoma (OTSCC) resulted in aggressive multi-modality management less
      effective. Here, we report for the first time that a panel of potential markers
      identified from tongue tumor samples using two-dimensional-differential-in-gel
      electrophoresis (2D-DIGE). Our approach of combining 2D-DIGE with tandem mass
      spectrometry identified 24 candidate proteins including cofilins, myosin light
      chain family members, annexins, serpins, HSPs and tropomyosins, with significant
      differential expression in tongue carcinomas as compared with their matched
      adjacent normal tissues. The expression levels of the identified proteins were
      further validated in larger cohort of Indian samples using qPCR. Most of the
      differentially regulated proteins are involved in actin cytoskeletal dynamics,
      drug resistance, immune system, inflammation and apoptotic signalling pathways
      and are known to play critical role in oral tumorigenesis. Taken together, the
      results from present investigation provide a valuable base for understanding the
      development and progression of OTSCC. The validated panel of proteins may be used
      as potential biomarkers for early detection as well as in predicting therapeutic
      outcome of OTSCC.

PMID- 29371636
TI  - Topological Valley Transport in Two-dimensional Honeycomb Photonic Crystals.
AB  - Two-dimensional photonic crystals, in analogy to AB/BA stacking bilayer graphene
      in electronic system, are studied. Inequivalent valleys in the momentum space for
      photons can be manipulated by simply engineering diameters of cylinders in a
      honeycomb lattice. The inequivalent valleys in photonic crystal are selectively
      excited by a designed optical chiral source and bulk valley polarizations are
      visualized. Unidirectional valley interface states are proved to exist on a
      domain wall connecting two photonic crystals with different valley Chern numbers.
      With the similar optical vortex index, interface states can couple with bulk
      valley polarizations and thus valley filter and valley coupler can be designed.
      Our simple dielectric PC scheme can help to exploit the valley degree of freedom
      for future optical devices.

PMID- 29371637
TI  - Cell death-based approaches in treatment of the urinary tract-associated
      diseases: a fight for survival in the killing fields.
AB  - Urinary tract-associated diseases comprise a complex set of disorders with a
      variety of etiologic agents and therapeutic approaches and a huge global burden
      of disease, estimated at around 1 million deaths per year. These diseases include
      cancer (mainly prostate, renal, and bladder), urinary tract infections, and
      urolithiasis. Cell death plays a key role in the pathogenesis and therapy of
      these conditions. During urinary tract infections, invading bacteria may either
      promote or prevent host cell death by interfering with cell death pathways. This
      has been studied in detail for uropathogenic E. coli (UPEC). Inhibition of host
      cell death may allow intracellular persistence of live bacteria, while promoting
      host cell death causes tissue damage and releases the microbes. Both crystals and
      urinary tract obstruction lead to tubular cell death and kidney injury. Among the
      pathomechanisms, apoptosis, necroptosis, and autophagy represent key processes.
      With respect to malignant disorders, traditional therapeutic efforts have focused
      on directly promoting cancer cell death. This may exploit tumor-specific
      characteristics, such as targeting Vascular Endothelial Growth Factor (VEGF)
      signaling and mammalian Target of Rapamycin (mTOR) activity in renal cancer and
      inducing survival factor deprivation by targeting androgen signaling in prostate
      cancer. An area of intense research is the use of immune checkpoint inhibitors,
      aiming at unleashing the full potential of immune cells to kill cancer cells. In
      the future, this may be combined with additional approaches exploiting intrinsic
      sensitivities to specific modes of cell death such as necroptosis and
      ferroptosis. Here, we review the contribution of diverse cell death mechanisms to
      the pathogenesis of urinary tract-associated diseases as well as the potential
      for novel therapeutic approaches based on an improved molecular understanding of
      these mechanisms.

PMID- 29371638
TI  - Characterization of Nanodiamond-based anti-HIV drug Delivery to the Brain.
AB  - Human Immunodeficiency Virus Type 1 (HIV-1) remains one of the leading causes of
      death worldwide. Present combination antiretroviral therapy has substantially
      improved HIV-1 related pathology. However, delivery of therapeutic agents to the
      HIV reservoir organ like Central nervous system (CNS) remains a major challenge
      primarily due to the ineffective transmigration of drugs through Blood Brain
      Barrier (BBB). The recent advent of nanomedicine-based drug delivery has
      stimulated the development of innovative systems for drug delivery. In this
      regard, particular focus has been given to nanodiamond due to its natural
      biocompatibility and non-toxic nature-making it a more efficient drug carrier
      than other carbon-based materials. Considering its potential and importance, we
      have characterized unmodified and surface-modified (-COOH and -NH2) nanodiamond
      for its capacity to load the anti-HIV-1 drug efavirenz and cytotoxicity, in
      vitro. Overall, our study has established that unmodified nanodiamond conjugated
      drug formulation has significantly higher drug loading capacity than surface
      modified nanodiamond with minimum toxicity. Further, this nanodrug formulation
      was characterized by its drug dissolution profile, transmigration through the
      BBB, and its therapeutic efficacy. The present biological characterizations
      provide a foundation for further study of in-vivo pharmacokinetics and
      pharmacodynamics of nanodiamond-based anti-HIV drugs.

PMID- 29371639
TI  - Application of Sustainable Natural Resources in Agriculture: Acaricidal and
      Enzyme Inhibitory Activities of Naphthoquinones and Their Analogs against
      Psoroptes cuniculi.
AB  - As important secondary plant metabolites, naphthoquinones exhibit a wide range of
      biological activities. However, their potential as sustainable alternatives to
      synthetic acaricides has not been studied. This study for the first time
      investigates the acaricidal activity of naphthoquinones against Psoroptes
      cuniculi in vitro. Furthermore, the in vivo activity, the skin irritation
      effects, the cytotoxicity and the inhibitory activities against mite
      acetylcholinesterase (AChE) and glutathione S-transferase (GST) of the two
      compounds that displayed the best insecticidal activity in vitro were evaluated.
      Among fourteen naphthoquinones and their analogs, juglone and plumbagin were
      observed to possess the strongest acaricidal activities against P. cuniculi with
      LC50 values of 20.53 ppm and 17.96 ppm, respectively, at 24 h. After three
      treatments, these two chemicals completely cured naturally infested rabbits in
      vivo within 15 days, and no skin irritation was found in any of the treated
      rabbits. Compared to plumbagin, juglone presented no or weak cytotoxicity against
      HL-7702 cells. Moreover, these two chemicals significantly inhibited AChE and GST
      activity. These results indicate that juglone has promising toxicity against P.
      cuniculi, is safe for both humans and animals at certain doses, and could be used
      as a potential alternative bio-acaricide for controlling the development of
      psoroptic mange in agricultural applications.

PMID- 29371641
TI  - Dairy products and total calcium intake at 13 years of age and its association
      with obesity at 21 years of age.
AB  - BACKGROUND/OBJECTIVES: Dairy products and specifically calcium have been
      suggested to play a role in obesity development but more longitudinal evidence is
      still needed. The objective of this study was to assess the association between
      dairy products and total calcium intake at age 13 and body mass index at age 21.
      SUBJECTS/METHODS: This longitudinal study included 2159 individuals from the
      Epidemiological Health Investigation of Teenagers cohort (EPITeen), Porto,
      Portugal, evaluated at ages 13 and 21. Assessment consisted of anthropometrics
      measurements and structured questionnaires namely a semi-quantitative food
      frequency questionnaire to appraise food consumption in the past 12 months.
      Linear regression models were run in 941 individuals with complete information of
      confounders: gender, follow-up period, parents' education, physical activity,
      energy, and total calcium intake. RESULTS: Negative association was found on
      total calcium intake at age 13 with BMI at age 21 (model 0: beta = -0.059 (95%
      CI: -0.113, -0.004) and model 1: -0.057 (95% CI: -0.113, -0.002)), however, no
      statistically significant association was found when adjusting for energy intake
      (model 2: beta = -0.031 (95% CI: -0.110, 0.047). There were no associations
      between milk, yogurt, and cheese consumption at age 13 and BMI at age 21 when
      adjusting for confounders. CONCLUSIONS: This study did not support an independent
      effect of dairy products or total calcium intake in adolescence on later early
      adulthood adiposity.

PMID- 29371640
TI  - Clinical utility gene card for McArdle disease.
AB  - Name of the disease (synonyms) McArdle disease (glycogenosis type V; glycogen
      storage disease V (GSDV); PYGM deficiency; muscle glycogen phosphorylase
      deficiency; myophosphorylase deficiency). OMIM# of the disease #232600. Name of
      the analysed genes or DNA/chromosome segments Muscle glycogen phosphoryalse
      (PYGM). OMIM# of the gene(s) #608455.Review of the analytical and clinical
      validity as well as of the clinical utility of DNA-based testing for variants in
      the PYGM gene(s) in? diagnostic,? predictive and? prenatal settings and for? risk
      assessment in relatives.

PMID- 29371642
TI  - Isolation and characterization of novel mutations in the pSC101 origin that
      increase copy number.
AB  - pSC101 is a narrow host range, low-copy plasmid commonly used for genetically
      manipulating Escherichia coli. As a byproduct of a genetic screen for a more
      sensitive lactam biosensor, we identified multiple novel mutations that increase
      the copy number of plasmids with the pSC101 origin. All mutations identified in
      this study occurred on plasmids which also contained at least one mutation
      localized to the RepA protein encoded within the origin. Homology modelling
      predicts that many of these mutations occur within the dimerization interface of
      RepA. Mutant RepA resulted in plasmid copy numbers between ~31 and ~113
      copies/cell, relative to ~5 copies/cell in wild-type pSC101 plasmids. Combining
      the mutations that were predicted to disrupt multiple contacts on the
      dimerization interface resulted in copy numbers of ~500 copies/cell, while also
      attenuating growth in host strains. Fluorescent protein production expressed from
      an arabinose-inducible promoter on mutant origin derived plasmids did correlate
      with copy number. Plasmids harboring RepA with one of two mutations, E83K and
      N99D, resulted in fluorescent protein production similar to that from p15a- (~20
      copies/cell) and ColE1- (~31 copies/cell) based plasmids, respectively. The
      mutant copy number variants retained compatibility with p15a, pBBR, and ColE1
      origins of replication. These pSC101 variants may be useful in future metabolic
      engineering efforts that require medium or high-copy vectors compatible with p15a
      and ColE1-based plasmids.

PMID- 29371643
TI  - Pharmacokinetic parameters explain the therapeutic activity of antimicrobial
      agents in a silkworm infection model.
AB  - Poor pharmacokinetic parameters are a major reason for the lack of therapeutic
      activity of some drug candidates. Determining the pharmacokinetic parameters of
      drug candidates at an early stage of development requires an inexpensive animal
      model with few associated ethical issues. In this study, we used the silkworm
      infection model to perform structure-activity relationship studies of an
      antimicrobial agent, GPI0039, a novel nitrofuran dichloro-benzyl ester, and
      successfully identified compound 5, a nitrothiophene dichloro-benzyl ester, as a
      potent antimicrobial agent with superior therapeutic activity in the silkworm
      infection model. Further, we compared the pharmacokinetic parameters of compound
      5 with a nitrothiophene benzyl ester lacking chlorine, compound 7, that exerted
      similar antimicrobial activity but had less therapeutic activity in silkworms,
      and examined the metabolism of these antimicrobial agents in human liver
      fractions in vitro. Compound 5 had appropriate pharmacokinetic parameters, such
      as an adequate half-life, slow clearance, large area under the curve, low volume
      of distribution, and long mean residence time, compared with compound 7, and was
      slowly metabolized by human liver fractions. These findings suggest that the
      therapeutic effectiveness of an antimicrobial agent in the silkworms reflects
      appropriate pharmacokinetic properties.

PMID- 29371644
TI  - Recombinant yeast and human cells as screening tools to search for antibacterial
      agents targeting the transcription termination factor Rho.
AB  - The alarming issue of antibiotic resistance expansion requires a continuous
      search for new and efficient antibacterial agents. Here we describe the design of
      new tools to screen for target-specific inhibitors of the bacterial Rho factor
      directly inside eukaryotic cells. Rho factor is a global regulator of gene
      expression which is essential to most bacteria, especially Gram-negative. Since
      Rho has no functional or structural homolog in eukaryotes, it constitutes a
      valuable and well known bacterial target as evidenced by its inhibition by the
      natural antibiotic, Bicyclomycin. Our screening tools are based on perturbation
      of mRNA processing and packaging reactions in the nucleus of eukaryotic cells by
      the RNA-dependent helicase/translocase activity of bacterial Rho factor leading
      to a growth defect phenotype. In this approach, any compound that impedes Rho
      activity should restore growth to yeast or human cells expressing Rho protein,
      providing valuable means to screen for target-specific antibacterial agents
      within the environment of a eukaryotic cell. The yeast tool expressing E. coli
      Rho factor was validated using Bicyclomycin as the control antibacterial agent.
      The validation of the screening tool was further extended with a stable human
      cell line expressing Rho factor conditionally. Finally, we show that Rho factors
      from different bacterial pathogens can also be designed as yeast-based screening
      tools which can reveal subtle variations in the functional features of the
      proteins.

PMID- 29371645
TI  - Study of the soluble salts formation in a recently restored house of Pompeii by
      in-situ Raman spectroscopy.
AB  - The walls and mural paintings of Pompeii exposed directly to the rainfalls are
      the most impacted in view of the observed decay. However, there are also wall
      paintings in protected rooms showing evidences of decaying. The aim of this
      research was to study the salts formed in such protected wall paintings only by
      non-invasive and in-situ Raman spectroscopy to understand their decaying
      processes. The perystile of the House of the Gilded Cupids (Regio VI, Insula 16),
      one of the most important houses of Pompeii was studied. Although an exhaustive
      restoration was carried out in 2004, a new conservation treatment was needed in
      2013 and only two years later, extensive crystallizations of soluble salts were
      again threatening several of the restored surfaces, thus, the presence of an
      unsolved degradation pathway was deduced. Thank to the proposed methodology, it
      was pointed out that the key is the acidified rainfall impact in the non
      protected backside of the walls containing the wall paintings. Thus, a new
      concept in the preservation of the houses of Pompeii is provided, in which the
      need of the protection of those walls from both sides is suggested to avoid the
      movement of water through the pores of the walls.

PMID- 29371646
TI  - Alternating Droplet Formation by using Tapered Channel Geometry.
AB  - The ability to produce a controlled sequence of alternating droplets from two
      separate sources inside a microfluidic system brings several advantages in
      microfluidic analysis. The effectiveness of this technique for use in an
      application depends on the ability of the device to replicate the pattern
      continuously and accurately. In this work we studied the effect of the dispersed
      phase channel geometry on generating a repeating pattern of alternating droplets
      in a cross junction microfluidic device. By measuring the radius of curvature of
      a droplet at the time of break up, and calculating the Laplace pressure using
      these values, we analyzed how the angle of taper of the dispersed phase inlet
      channel has an influence on the pattern repetition and uniformity of formed
      droplet size and spacing in between. The performance of devices with different
      angle of taper values were studied experimentally. This comparative study
      indicated that the ability of a cross junction device to generate alternating
      droplets with uniform size and spacing is highly dependent on the angle of taper
      of the inlet channels; and it improves with larger taper angles.

PMID- 29371647
TI  - Laser-accelerated particle beams for stress testing of materials.
AB  - Laser-driven particle acceleration, obtained by irradiation of a solid target
      using an ultra-intense (I > 1018 W/cm2) short-pulse (duration <1 ps) laser, is a
      growing field of interest, in particular for its manifold potential applications
      in different domains. Here, we provide experimental evidence that laser-generated
      particles, in particular protons, can be used for stress testing materials and
      are particularly suited for identifying materials to be used in harsh conditions.
      We show that these laser-generated protons can produce, in a very short time
      scale, a strong mechanical and thermal damage, that, given the short irradiation
      time, does not allow for recovery of the material. We confirm this by analyzing
      changes in the mechanical, optical, electrical, and morphological properties of
      five materials of interest to be used in harsh conditions.

PMID- 29371648
TI  - Re-initiation of bottom water formation in the East Sea (Japan Sea) in a warming
      world.
AB  - The East Sea (Japan Sea), a small marginal sea in the northwestern Pacific, is
      ventilated deeply down to the bottom and sensitive to changing surface
      conditions. Addressing the response of this marginal sea to the hydrological
      cycle and atmospheric forcing would be helpful for better understanding present
      and future environmental changes in oceans at the global and regional scales.
      Here, we present an analysis of observations revealing a slowdown of the long
      term deepening in water boundaries associated with changes of water formation
      rate. Our results indicate that bottom (central) water formation has been
      enhanced (reduced) with more (less) oxygen supply to the bottom (central) layer
      since the 2000s. This paper presents a new projection that allows a three-layered
      deep structure, which retains bottom water, at least until 2040, contrasting
      previous results. This projection considers recent increase of slope convections
      mainly due to the salt supply via air-sea freshwater exchange and sea ice
      formation and decrease of open-ocean convections evidenced by reduced mixed layer
      depth in the northern East Sea, resulting in more bottom water and less central
      water formations. Such vigorous changes in water formation and ventilation
      provide certain implications on future climate changes.

PMID- 29371649
TI  - Studies on the Proteome of Human Hair - Identification of Histones and Deamidated
      Keratins.
AB  - Human hair is laminar-fibrous tissue and an evolutionarily old keratinization
      product of follicle trichocytes. Studies on the hair proteome can give new
      insights into hair function and lead to the development of novel biomarkers for
      hair in health and disease. Human hair proteins were extracted by detergent and
      detergent-free techniques. We adopted a shotgun proteomics approach, which
      demonstrated a large extractability and variety of hair proteins after detergent
      extraction. We found an enrichment of keratin, keratin-associated proteins
      (KAPs), and intermediate filament proteins, which were part of protein networks
      associated with response to stress, innate immunity, epidermis development, and
      the hair cycle. Our analysis also revealed a significant deamidation of keratin
      type I and II, and KAPs. The hair shafts were found to contain several types of
      histones, which are well known to exert antimicrobial activity. Analysis of the
      hair proteome, particularly its composition, protein abundances, deamidated hair
      proteins, and modification sites, may offer a novel approach to explore potential
      biomarkers of hair health quality, hair diseases, and aging.

PMID- 29371650
TI  - Astrocytes modulate brainstem respiratory rhythm-generating circuits and
      determine exercise capacity.
AB  - Astrocytes are implicated in modulation of neuronal excitability and synaptic
      function, but it remains unknown if these glial cells can directly control
      activities of motor circuits to influence complex behaviors in vivo. This study
      focused on the vital respiratory rhythm-generating circuits of the preBotzinger
      complex (preBotC) and determined how compromised function of local astrocytes
      affects breathing in conscious experimental animals (rats). Vesicular release
      mechanisms in astrocytes were disrupted by virally driven expression of either
      the dominant-negative SNARE protein or light chain of tetanus toxin. We show that
      blockade of vesicular release in preBotC astrocytes reduces the resting breathing
      rate and frequency of periodic sighs, decreases rhythm variability, impairs
      respiratory responses to hypoxia and hypercapnia, and dramatically reduces the
      exercise capacity. These findings indicate that astrocytes modulate the activity
      of CNS circuits generating the respiratory rhythm, critically contribute to
      adaptive respiratory responses in conditions of increased metabolic demand and
      determine the exercise capacity.

PMID- 29371651
TI  - In silico profiling of systemic effects of drugs to predict unexpected
      interactions.
AB  - Identifying unexpected drug interactions is an essential step in drug
      development. Most studies focus on predicting whether a drug pair interacts or is
      effective on a certain disease without considering the mechanism of action (MoA).
      Here, we introduce a novel method to infer effects and interactions of drug pairs
      with MoA based on the profiling of systemic effects of drugs. By investigating
      propagated drug effects from the molecular and phenotypic networks, we
      constructed profiles of 5,441 approved and investigational drugs for 3,833
      phenotypes. Our analysis indicates that highly connected phenotypes between drug
      profiles represent the potential effects of drug pairs and the drug pairs with
      strong potential effects are more likely to interact. When applied to drug
      interactions with verified effects, both therapeutic and adverse effects have
      been successfully identified with high specificity and sensitivity. Finally,
      tracing drug interactions in molecular and phenotypic networks allows us to
      understand the MoA.

PMID- 29371653
TI  - Nuclear pores: the gate to neurodegeneration.

PMID- 29371652
TI  - Phage or foe: an insight into the impact of viral predation on microbial
      communities.
AB  - Since their discovery, bacteriophages have been traditionally regarded as the
      natural enemies of bacteria. However, recent advances in molecular biology
      techniques, especially data from "omics" analyses, have revealed that the
      interplay between bacterial viruses and their hosts is far more intricate than
      initially thought. On the one hand, we have become more aware of the impact of
      viral predation on the composition and genetic makeup of microbial communities
      thanks to genomic and metagenomic approaches. Moreover, data obtained from
      transcriptomic, proteomic, and metabolomic studies have shown that responses to
      phage predation are complex and diverse, varying greatly depending on the
      bacterial host, phage, and multiplicity of infection. Interestingly, phage
      exposure may alter different phenotypes, including virulence and biofilm
      formation. The complexity of the interactions between microbes and their viral
      predators is also evidenced by the link between quorum-sensing signaling pathways
      and bacteriophage resistance. Overall, new data increasingly suggests that both
      temperate and virulent phages have a positive effect on the evolution and
      adaptation of microbial populations. From this perspective, further research is
      still necessary to fully understand the interactions between phage and host under
      conditions that allow co-existence of both populations, reflecting more
      accurately the dynamics in natural microbial communities.

PMID- 29371656
TI  - John Lisman 1944-2017.

PMID- 29371655
TI  - Skip the salt: your brain might thank you.

PMID- 29371657
TI  - Pamela Sklar 1959-2017.

PMID- 29371654
TI  - Integrating new findings and examining clinical applications of pattern
      separation.
AB  - Pattern separation, the ability to independently represent and store similar
      experiences, is a crucial facet of episodic memory. Growing evidence suggests
      that the hippocampus possesses unique circuitry that is computationally capable
      of resolving mnemonic interference by using pattern separation. In this Review,
      we discuss recent advances in the understanding of this process and evaluate the
      caveats and limitations of linking across animal and human studies. We summarize
      clinical and translational studies using methods that are sensitive to pattern
      separation impairments, an approach that stems from the fact that the hippocampus
      is a major site of disruption in many brain disorders. We critically evaluate the
      assumptions that guide fundamental and translational studies in this area.
      Finally, we suggest guidelines for future research and offer ways to overcome
      potential interpretational challenges to increase the utility of pattern
      separation as a construct that can further understanding of both memory processes
      and brain disease.

PMID- 29371658
TI  - Grid cells map the visual world.

PMID- 29371659
TI  - Same path, different beginnings.

PMID- 29371660
TI  - Natural Intermediate Band in I 2 -II-IV-VI4 Quaternary Chalcogenide
      Semiconductors.
AB  - An intermediate band in the band gap of semiconductors is fundamental to the
      development of the intermediate band solar cells, but it is usually produced
      artificially, which imposes technical challenges on the experimental realization.
      Here we found that there are natural intermediate bands in the band gaps of the
      I2-II-IV-VI4 quaternary chalcogenide semiconductors such as Cu2ZnSnS4 and
      Ag2ZnSnSe4, which had been proposed as promising light-absorber semiconductors in
      thin film solar cells. By first-principles calculations, we found the lowest
      conduction band of these I2-II-IV-VI4 semiconductors in the kesterite structure
      is isolated (a lone band, resulting from the energy separation between Sn 5s and
      5p states), which can be viewed as a natural intermediate band. The gap between
      the intermediate band and higher-energy conduction band can be increased through
      changing the crystal structure from the zincblende-derived kesterite structure to
      the wurtzite-derived wurtzite-kesterite structure. In contrast, the intermediate
      conduction band gap shrinks when the component element Sn is replaced by Ge
      (Cu2ZnGeS4), and the gap even disappears (intermediate band disappear) when Sn is
      replaced by Si (Cu2ZnSiS4). Through tuning the intermediate-conduction and
      intermediate-valence band gaps, we show that the wurtzite-kesterite structured
      Ag2ZnSnSe4 may be a potential light-absorber semiconductor in intermediate band
      solar cells.

PMID- 29371661
TI  - Cellular death, reactive oxygen species (ROS) and diabetic complications.
AB  - Chronic or intermittent hyperglycemia is associated with the development of
      diabetic complications. Several signaling pathways can be altered by having
      hyperglycemia in different tissues, producing oxidative stress, the formation of
      advanced glycation end products (AGEs), as well as the secretion of the pro
      inflammatory cytokines and cellular death (pathological autophagy and/or
      apoptosis). However, the signaling pathways that are directly triggered by
      hyperglycemia appear to have a pivotal role in diabetic complications due to the
      production of reactive oxygen species (ROS), oxidative stress, and cellular
      death. The present review will discuss the role of cellular death in diabetic
      complications, and it will suggest the cause and the consequences between the
      hyperglycemia-induced signaling pathways and cell death. The signaling pathways
      discussed in this review are to be described step-by-step, together with their
      respective inhibitors. They involve diacylglycerol, the activation of protein
      kinase C (PKC) and NADPH-oxidase system, and the consequent production of ROS.
      This was initially entitled the "dangerous metabolic route in diabetes". The
      historical usages and the recent advancement of new drugs in controlling possible
      therapeutical targets have been highlighted, in order to evaluate the evolution
      of knowledge in this sensitive area. It has recently been shown that the
      metabolic responses to stimuli (i.e., hyperglycemia) involve an integrated
      network of signaling pathways, in order to define the exact responses. Certain
      new drugs have been experimentally tested-or suggested and proposed-for their
      ability to modulate the possible biochemical therapeutical targets for the
      downregulation of retinopathy, nephropathy, neuropathy, heart disease,
      angiogenesis, oxidative stress, and cellular death. The aim of this study was to
      critically and didactically evaluate the exact steps of these signaling pathways
      and hence mark the indicated sites for the actions of such drugs and their
      possible consequences. This review will emphasize, besides others, the
      therapeutical targets for controlling the signaling pathways, when aimed at the
      downregulation of ROS generation, oxidative stress, and, consequently, cellular
      death-with all of these conditions being a problem in diabetes.

PMID- 29371662
TI  - Crystal structure of lipid A disaccharide synthase LpxB from Escherichia coli.
AB  - Most Gram-negative bacteria are surrounded by a glycolipid called
      lipopolysaccharide (LPS), which forms a barrier to hydrophobic toxins and, in
      pathogenic bacteria, is a virulence factor. During LPS biosynthesis, a membrane
      associated glycosyltransferase (LpxB) forms a tetra-acylated disaccharide that is
      further acylated to form the membrane anchor moiety of LPS. Here we solve the
      structure of a soluble and catalytically competent LpxB by X-ray crystallography.
      The structure reveals that LpxB has a glycosyltransferase-B family fold but with
      a highly intertwined, C-terminally swapped dimer comprising four domains. We
      identify key catalytic residues with a product, UDP, bound in the active site, as
      well as clusters of hydrophobic residues that likely mediate productive membrane
      association or capture of lipidic substrates. These studies provide the basis for
      rational design of antibiotics targeting a crucial step in LPS biosynthesis.

PMID- 29371664
TI  - Carbon nanofibers (CNFs) supported cobalt- nickel sulfide (CoNi2S4) nanoparticles
      hybrid anode for high performance lithium ion capacitor.
AB  - Lithium ion capacitors possess an ability to bridge the gap between lithium ion
      battery and supercapacitor. The main concern of fabricating lithium ion
      capacitors is poor rate capability and cyclic stability of the anode material
      which uses sluggish faradaic reactions to store an electric charge. Herein, we
      have fabricated high performance hybrid anode material based on carbon nanofibers
      (CNFs) and cobalt-nickel sulfide (CoNi2S4) nanoparticles via simple
      electrospinning and electrodeposition methods. Porous and high conducting
      CNF@CoNi2S4 electrode acts as an expressway network for electronic and ionic
      diffusion during charging-discharging processes. The effect of anode to cathode
      mass ratio on the performance has been studied by fabricating lithium ion
      capacitors with different mass ratios. The surface controlled contribution of
      CNF@CoNi2S4 electrode was 73% which demonstrates its excellent rate capability.
      Lithium ion capacitor fabricated with CNF@CoNi2S4 to AC mass ratio of 1:2.6
      showed excellent energy density of 85.4 Wh kg-1 with the power density of 150 W
      kg-1. Also, even at the high power density of 15 kW kg-1, the cell provided the
      energy density of 35 Wh kg-1. This work offers a new strategy for designing high
      performance hybrid anode with the combination of simple and cost effective
      approaches.

PMID- 29371663
TI  - High-resolution spatiotemporal transcriptome mapping of tomato fruit development
      and ripening.
AB  - Tomato (Solanum lycopersicum) is an established model for studying fruit biology;
      however, most studies of tomato fruit growth and ripening are based on
      homogenized pericarp, and do not consider the internal tissues, or the expression
      signatures of individual cell and tissue types. We present a spatiotemporally
      resolved transcriptome analysis of tomato fruit ontogeny, using laser
      microdissection (LM) or hand dissection coupled with RNA-Seq analysis. Regulatory
      and structural gene networks, including families of transcription factors and
      hormone synthesis and signaling pathways, are defined across tissue and
      developmental spectra. The ripening program is revealed as comprising gradients
      of gene expression, initiating in internal tissues then radiating outward, and
      basipetally along a latitudinal axis. We also identify spatial variations in the
      patterns of epigenetic control superimposed on ripening gradients. Functional
      studies elucidate previously masked regulatory phenomena and relationships,
      including those associated with fruit quality traits, such as texture, color,
      aroma, and metabolite profiles.

PMID- 29371666
TI  - The creation of electric wind due to the electrohydrodynamic force.
AB  - Understanding the interactions between ionized matter and neutral particles is a
      prerequisite for discovering their impact on natural phenomena. One such
      phenomenon is the electric wind, which supposedly occurs due to the charged
      particle-neutral coupling in systems of weakly ionized gases, but this mechanism
      remains unclear. Here, we report direct evidence that electric wind is caused by
      an electrohydrodynamic force generated by the charged particle drag as a result
      of the momentum transfer from electrons/ions to neutrals. The model experiment is
      based on a pulsed plasma jet as a source of weakly ionized gases generated in the
      helium gas at atmospheric pressure using Schlieren photography. Studying the
      helium gas flow trajectories at different discharge parameters allows one to
      distinguish between the effects of streamer propagation or space charge drift
      causing the electric wind as well as to determine the role of electrons and
      (positive) ions in wind generation.

PMID- 29371665
TI  - Lsd1 regulates skeletal muscle regeneration and directs the fate of satellite
      cells.
AB  - Satellite cells are muscle stem cells required for muscle regeneration upon
      damage. Of note, satellite cells are bipotent and have the capacity to
      differentiate not only into skeletal myocytes, but also into brown adipocytes.
      Epigenetic mechanisms regulating fate decision and differentiation of satellite
      cells during muscle regeneration are not yet fully understood. Here, we show that
      elevated levels of lysine-specific demethylase 1 (Kdm1a, also known as Lsd1) have
      a beneficial effect on muscle regeneration and recovery after injury, since Lsd1
      directly regulates key myogenic transcription factor genes. Importantly,
      selective Lsd1 ablation or inhibition in Pax7-positive satellite cells, not only
      delays muscle regeneration, but changes cell fate towards brown adipocytes. Lsd1
      prevents brown adipocyte differentiation of satellite cells by repressing
      expression of the novel pro-adipogenic transcription factor Glis1. Together,
      downregulation of Glis1 and upregulation of the muscle-specific transcription
      program ensure physiological muscle regeneration.

PMID- 29371667
TI  - Distinct distribution patterns of ammonia-oxidizing archaea and bacteria in
      sediment and water column of the Yellow River estuary.
AB  - Ammonia oxidation is a critical process of estuarine nitrogen cycling involving
      ammonia-oxidizing archaea (AOA) and bacteria (AOB). However, the distribution
      patterns of ammonia-oxidizing microorganisms (AOMs) between different habitats in
      the same area remain unclear. The present study investigated the AOMs' abundance
      and community compositions in both sediment and water habitats of the Yellow
      River estuary. Quantitative PCR (qPCR) revealed that AOA showed significant
      higher abundance than AOB both in sediment and water samples. AOA and AOB
      abundance distribution trends were consistent in sediment but distinct in water
      along the sampling sites. Clone library-based analyses showed that AOA sequences
      were affiliated with Nitrososphaera, Nitrosopumilus and Nitrosotalea clusters.
      Generally, Nitrososphaera was predominant in sediment, while Nitrosopumilus and
      Nitrosotalea dominated in water column. AOB sequences were classified into genera
      Nitrosospira and Nitrosomonas, and Nitrosospira dominated in both habitats.
      Principal coordinate analysis (PCoA) also indicated AOA community structures
      exhibited significant differences between two habitats, while AOB were not.
      Ammonium and carbon contents were the potential key factors to influence AOMs'
      abundance and compositions in sediment, while no measured variables were
      determined to have major influences on communities in water habitat. These
      findings increase the understanding of the AOMs' distribution patterns in
      estuarine ecosystems.

PMID- 29371668
TI  - The compositional and nano-structural basis of fracture healing in healthy and
      osteoporotic bone.
AB  - Osteoporosis, a prevalent metabolic bone disorder, predisposes individuals to
      increased susceptibility to fractures. It is also, somewhat controversially,
      thought to delay or impair the regenerative response. Using high-resolution
      Fourier-transform infrared spectroscopy and small/wide-angle X-ray scattering we
      sought to answer the following questions: Does the molecular composition and the
      nano-structure in the newly regenerated bone differ between healthy and
      osteoporotic environments? And how do pharmacological treatments, such as bone
      morphogenetic protein 7 (BMP-7) alone or synergistically combined with
      zoledronate (ZA), alter callus composition and nano-structure in such
      environments? Cumulatively, on the basis of compositional and nano-structural
      characterizations of newly formed bone in an open-osteotomy rat model, the
      healing response in untreated healthy and ovariectomy-induced osteoporotic
      environments was fundamentally the same. However, the BMP-7 induced osteogenic
      response resulted in greater heterogeneity in the nano-structural crystal
      dimensions and this effect was more pronounced with osteoporosis. ZA mitigated
      the effects of the upregulated catabolism induced by both BMP-7 and an
      osteoporotic bone environment. The findings contribute to our understanding of
      how the repair processes in healthy and osteoporotic bone differ in both
      untreated and treated contexts and the data presented represents the most
      comprehensive study of fracture healing at the nanoscale undertaken to date.

PMID- 29371670
TI  - Simultaneous bilateral total knee arthroplasty in patients with end-stage
      hemophilic arthropathy: a mean follow-up of 6 years.
AB  - To investigate the safety, cost-effectiveness, and clinical outcomes of
      simultaneous bilateral total knee arthroplasty (TKA) in hemophilic arthropathy
      (HA), the requirements for transfusions, complications, costs, hospital stays,
      Hospital for Special Surgery (HSS) knee scores, knee range of motion (ROM) and
      revision rates were compared between simultaneous bilateral and unilateral TKA in
      HA patients. A total of 36 patients and 54 knees were included. Compared to the
      unilateral group, the bilateral group did not require more transfusions (2.39 +/-
      3.13 vs 0.83 +/- 1.38 units of RBCs, p > 0.05) or consumption of coagulation
      factors (50091.67 +/- 25168.5 vs 46477.78 +/- 11348.32 IU, p > 0.05),
      complications rate (13/36 vs 6/18, p > 0.05), hospital stay (32.39 +/- 19.77 vs
      29.11 +/- 12.67 days, p > 0.05), or costs excluding prostheses (14945.41 +/-
      6634.35 vs 14742.12 +/- 5746.78 US dollars, p > 0.05). Additionally, the two
      groups exhibited similar medium-term knee HSS scores (83.67 +/- 7.11 vs 81.00 +/-
      10.35, p > 0.05) and ROM (89.39 degrees  +/- 13.66 degrees  vs 88.91 degrees  +/-
      12.90 degrees , p > 0.05). Our data indicate that bilateral TKA is a safe and
      cost-effective treatment for HA with similar medium-term results compared to
      unilateral TKA.

PMID- 29371669
TI  - Development of novel fluorescent histamine H1-receptor antagonists to study
      ligand-binding kinetics in living cells.
AB  - The histamine H1-receptor (H1R) is an important mediator of allergy and
      inflammation. H1R antagonists have particular clinical utility in allergic
      rhinitis and urticaria. Here we have developed six novel fluorescent probes for
      this receptor that are very effective for high resolution confocal imaging,
      alongside bioluminescence resonance energy transfer approaches to monitor H1R
      ligand binding kinetics in living cells. The latter technology exploits the
      opportunities provided by the recently described bright bioluminescent protein
      NanoLuc when it is fused to the N-terminus of a receptor. Two different
      pharmacophores (mepyramine or the fragment VUF13816) were used to generate
      fluorescent H1R antagonists conjugated via peptide linkers to the fluorophore
      BODIPY630/650. Kinetic properties of the probes showed wide variation, with the
      VUF13816 analogues having much longer H1R residence times relative to their
      mepyramine-based counterparts. The kinetics of these fluorescent ligands could
      also be monitored in membrane preparations providing new opportunities for future
      drug discovery applications.

PMID- 29371671
TI  - Development of a novel zebrafish xenograft model in ache mutants using liver
      cancer cell lines.
AB  - Acetylcholinesterase (AChE), an enzyme responsible for degradation of
      acetylcholine, has been identified as a prognostic marker in liver cancer.
      Although in vivo Ache tumorigenicity assays in mouse are present, no established
      liver cancer xenograft model in zebrafish using an ache mutant background exists.
      Herein, we developed an embryonic zebrafish xenograft model using epithelial
      (Hep3B) and mesenchymal (SKHep1) liver cancer cell lines in wild-type and ache
      sb55 sibling mutant larvae after characterization of cholinesterase expression
      and activity in cell lines and zebrafish larvae. The comparison of fluorescent
      signal reflecting tumor size at 3-days post-injection (dpi) revealed an enhanced
      tumorigenic potential and a reduced migration capacity in cancer cells injected
      into homozygous ache sb55 mutants when compared with the wild-type. Increased
      tumor load was confirmed using an ALU based tumor DNA quantification method
      modified for use in genotyped xenotransplanted zebrafish embryos. Confocal
      microscopy using the Huh7 cells stably expressing GFP helped identify the
      distribution of tumor cells in larvae. Our results imply that acetylcholine
      accumulation in the microenvironment directly or indirectly supports tumor growth
      in liver cancer. Use of this model system for drug screening studies holds
      potential in discovering new cholinergic targets for treatment of liver cancers.

PMID- 29371672
TI  - Moderate acute alcohol intoxication increases visual motion repulsion.
AB  - Among the serious consequences of alcohol abuse is the reduced ability to process
      visual information. Diminished vision from excessive consumption of alcohol has
      been implicated in industrial, home, and automobile accidents. Alcohol is also
      generally recognized as an inhibitor in the brain by potentiating GABA-ergic
      transmission. In this study, we focused on visual motion processing and explored
      whether moderate alcohol intoxication induced changes in inhibitory mediated
      motion repulsion in a center-surround configuration. We conducted a double-blind,
      placebo-controlled, within-subjects study on the effect of alcohol on visual
      motion repulsion. Each subject underwent three experimental conditions (no
      alcohol, placebo and moderate alcohol) on separate days. The order of the placebo
      and moderate alcohol conditions was counterbalanced. The results showed that the
      effects of the surround context on the perception of the center motion direction
      were similar in both the sober (no alcohol) and placebo conditions. However,
      contextual modulations were significantly stronger during intoxication compared
      to both the sober and placebo conditions. These results demonstrate that moderate
      alcohol consumption is associated with altered neural function in visual cortical
      areas and that motion repulsion deficits might reflect the inhibitory effects of
      alcohol on the central nervous system.

PMID- 29371673
TI  - Human Rhinovirus 3C protease cleaves RIPK1, concurrent with caspase 8 activation.
AB  - Human Rhinovirus (HRV) is a pathogen of significant medical importance, being a
      major cause of upper respiratory tract infections (common colds) as well as
      causing the majority of virus-induced asthma exacerbations. We investigated
      whether HRV could modulate apoptosis, an innate antiviral response. Apoptotic
      signals are generated either extrinsically or intrinsically and are propagated
      via caspase cascades that lead to cell death, reducing viral replication, which
      relies on cellular machinery. Using HRV16 infected cells, in combination with
      chemical inducers and inhibitors of extrinsic apoptosis we show that HRV16 3C
      protease cleaves a key intermediate in extrinsic apoptosis. Receptor-interacting
      protein kinase-1 (RIPK1), an extrinsic apoptosis adaptor protein, was cleaved by
      caspase 8, as expected, during chemical induction of apoptosis. RIPK1 was cleaved
      in HRV infection albeit at a different site. Caspase 8 activation, which is
      associated with extrinsic apoptosis, was concurrent with HRV 3C protease mediated
      cleavage of RIPK1, and potentially increased the accessibility of the HRV 3C
      cleavage site within RIPK1 in-vitro. The caspase 8 mediated RIPK1 cleavage
      product has a pro-apoptotic function, and further cleavage of this pro-apoptotic
      cleavage product by HRV 3C may provide a mechanism by which HRV limits apoptosis.

PMID- 29371674
TI  - Cell death-based treatment of various diseases: a fifty-year journey.

PMID- 29371675
TI  - Metasurfaced Reverberation Chamber.
AB  - The concept of metasurfaced reverberation chamber (RC) is introduced in this
      paper. It is shown that by coating the chamber wall with a rotating 1-bit random
      coding metasurface, it is possible to enlarge the test zone of the RC while
      maintaining the field uniformity as good as that in a traditional RC with
      mechanical stirrers. A 1-bit random coding diffusion metasurface is designed to
      obtain all-direction backscattering under normal incidence. Three specific cases
      are studied for comparisons, including a (traditional) mechanical stirrer RC, a
      mechanical stirrer RC with a fixed diffusion metasurface, and a RC with a
      rotating diffusion metasurface. Simulation results show that the compact rotating
      diffusion metasurface can act as a stirrer with good stirring efficiency. By
      using such rotating diffusion metasurface, the test region of the RC can be
      greatly extended.

PMID- 29371676
TI  - Assessment of the characteristics and biocompatibility of gelatin sponge
      scaffolds prepared by various crosslinking methods.
AB  - This comparative study aims to identify a biocompatible and effective crosslinker
      for preparing gelatin sponges. Glutaraldehyde (GTA), genipin (GP), 1-ethyl-3-(3
      dimethyl aminopropyl)carbodiimide (EDC), and microbial transglutaminase (mTG)
      were used as crosslinking agents. The physical properties of the prepared samples
      were characterized, and material degradation was studied in vitro with various
      proteases and in vivo through subcutaneous implantation of the sponges in rats.
      Adipose-derived stromal stem cells (ADSCs) were cultured and inoculated onto the
      scaffolds to compare the cellular biocompatibility of the sponges. Cellular
      seeding efficiency and digestion time of the sponges were also evaluated.
      Cellular viability and proliferation in scaffolds were analyzed by fluorescence
      staining and MTT assay. All the samples exhibited high porosity, good swelling
      ratio, and hydrolysis properties; however, material strength, hydrolysis, and
      enzymolytic properties varied among the samples. GTA-sponge and GP-sponge
      possessed high compressive moduli, and EDC-sponge exhibited fast degradation
      performance. GTA and GP sponge implants exerted strong in vivo rejections, and
      the former showed poor cell growth. mTG-sponge exhibited the optimal
      comprehensive performance, with good porosity, compressive modulus, anti
      degradation ability, and good biocompatibility. Hence, mTG-sponge can be used as
      a scaffold material for tissue engineering applications.

PMID- 29371677
TI  - A quiescent cell population replenishes mesenchymal stem cells to drive
      accelerated growth in mouse incisors.
AB  - The extent to which heterogeneity within mesenchymal stem cell (MSC) populations
      is related to function is not understood. Using the archetypal MSC in vitro
      surface marker, CD90/Thy1, here we show that 30% of the MSCs in the continuously
      growing mouse incisor express CD90/Thy1 and these cells give rise to 30% of the
      differentiated cell progeny during postnatal development. In adulthood, when
      growth rate homeostasis is established, the CD90/Thy1+ MSCs decrease dramatically
      in number. When adult incisors are cut, the growth rate increases to rapidly re
      establish tooth length and homeostasis. This accelerated growth rate correlates
      with the re-appearance of CD90/Thy+ MSCs and re-establishment of their
      contribution to cell differentiation. A population of Celsr1+ quiescent cells
      becomes mitotic following clipping and replenishes the CD90/Thy1 population. A
      sub-population of MSCs thus exists in the mouse incisor, distinguished by
      expression of CD90/Thy1 that plays a specific role only during periods of
      increased growth rate.

PMID- 29371678
TI  - Inwardly Rectifying Potassium (Kir) Channels Represent a Critical Ion Conductance
      Pathway in the Nervous Systems of Insects.
AB  - A complete understanding of the physiological pathways critical for proper
      function of the insect nervous system is still lacking. The recent development of
      potent and selective small-molecule modulators of insect inward rectifier
      potassium (Kir) channels has enabled the interrogation of the physiological role
      and toxicological potential of Kir channels within various insect tissue systems.
      Therefore, we aimed to highlight the physiological and functional role of neural
      Kir channels the central nervous system, muscular system, and neuromuscular
      system through pharmacological and genetic manipulations. Our data provide
      significant evidence that Drosophila neural systems rely on the inward
      conductance of K+ ions for proper function since pharmacological inhibition and
      genetic ablation of neural Kir channels yielded dramatic alterations of the CNS
      spike discharge frequency and broadening and reduced amplitude of the evoked EPSP
      at the neuromuscular junction. Based on these data, we conclude that neural Kir
      channels in insects (1) are critical for proper function of the insect nervous
      system, (2) represents an unexplored physiological pathway that is likely to
      shape the understanding of neuronal signaling, maintenance of membrane
      potentials, and maintenance of the ionic balance of insects, and (3) are capable
      of inducing acute toxicity to insects through neurological poisoning.

PMID- 29371679
TI  - A functional interplay between Delta133p53 and DeltaNp63 in promoting glycolytic
      metabolism to fuel cancer cell proliferation.
AB  - Although DeltaNp63 is known to promote cancer cell proliferation, the underlying
      mechanism behind its oncogenic function remains elusive. We report here a
      functional interplay between DeltaNp63 and Delta133p53. These two proteins are co
      overexpressed in a subset of human cancers and cooperate to promote cell
      proliferation. Mechanistically, Delta133p53 binds to DeltaNp63 and utilizes its
      transactivation domain to upregulate GLUT1, GLUT4, and PGM expression driving
      glycolysis. While increased glycolysis provides cancer cells with anabolic
      metabolism critical for proliferation and survival, it can be harnessed for
      selective cancer cell killing. Indeed, we show that tumors overexpressing both
      DeltaNp63 and Delta133p53 exhibit heightened sensitivity to vitamin C that
      accumulate to a lethal level due to accelerated uptake via overexpressed GLUT1.
      These observations offer a new therapeutic avenue that could be exploited for
      clinical applications.

PMID- 29371680
TI  - CHTM1, a novel metabolic marker deregulated in human malignancies.
AB  - A better understanding of the link between cellular metabolism and tumorigenesis
      is needed. Here, we report characterization of a novel protein named coiled-coil
      helix tumor and metabolism 1 (CHTM1). We have found that CHTM1 is associated with
      cancer and cellular metabolism. CHTM1 localizes to mitochondria and cytosol, and
      its deficiency in cancer cells results in decreased mitochondrial oxygen
      consumption and ATP levels as well as oxidative stress indicating mitochondrial
      dysfunction. CHTM1-deficient cancer cells display poor growth under
      glucose/glutamine-deprived conditions, whereas cells expressing increased levels
      of exogenous CHTM1 exhibit enhanced proliferation and survival under similar
      conditions. CHTM1 deficiency also leads to defects in lipid metabolism resulting
      in fatty acid accumulation, which explains poor growth of CHTM1-deficient cells
      under glucose/glutamine deprivation since nutrient deprivation increases
      dependency on lipids for energy generation. We also demonstrate that CHTM1
      mediates its effect via the PKC, CREB, and PGC-1alpha signaling axis, and
      cytosolic accumulation of CHTM1 during nutrient deprivation appears to be
      important for its effect on cellular signaling events. Furthermore, analyses of
      tissue specimens from 71 breast and 97 colon cancer patients show CHTM1
      expression to be upregulated in the majority of tumor specimens representing
      these malignancies. Collectively, our findings are highly significant because
      CHTM1 is a novel metabolic marker that is important for the growth of tumorigenic
      cells under limiting nutrient supplies and thus, links cellular metabolism and
      tumorigenesis.

PMID- 29371682
TI  - Real-time TIRF observation of vinculin recruitment to stretched alpha-catenin by
      AFM.
AB  - Adherens junctions (AJs) adaptively change their intensities in response to
      intercellular tension; therefore, they integrate tension generated by individual
      cells to drive multicellular dynamics, such as morphogenetic change in embryos.
      Under intercellular tension, alpha-catenin, which is a component protein of AJs,
      acts as a mechano-chemical transducer to recruit vinculin to promote actin
      remodeling. Although in vivo and in vitro studies have suggested that alpha
      catenin-mediated mechanotransduction is a dynamic molecular process, which
      involves a conformational change of alpha-catenin under tension to expose a
      cryptic vinculin binding site, there are no suitable experimental methods to
      directly explore the process. Therefore, in this study, we developed a novel
      system by combining atomic force microscopy (AFM) and total internal reflection
      fluorescence (TIRF). In this system, alpha-catenin molecules (residues 276-634;
      the mechano-sensitive M1-M3 domain), modified on coverslips, were stretched by
      AFM and their recruitment of Alexa-labeled full-length vinculin molecules,
      dissolved in solution, were observed simultaneously, in real time, using TIRF. We
      applied a physiologically possible range of tensions and extensions to alpha
      catenin and directly observed its vinculin recruitment. Our new system could be
      used in the fields of mechanobiology and biophysics to explore functions of
      proteins under tension by coupling biomechanical and biochemical information.

PMID- 29371684
TI  - 'To treat or not to treat': raising awareness on the effects of graft versus host
      disease drugs on musculoskeletal system.

PMID- 29371681
TI  - The effect of feature-based attention on flanker interference processing: An fMRI
      constrained source analysis.
AB  - The present study examined whether feature-based cueing affects early or late
      stages of flanker conflict processing using EEG and fMRI. Feature cues either
      directed participants' attention to the upcoming colour of the target or were
      neutral. Validity-specific modulations during interference processing were
      investigated using the N200 event-related potential (ERP) component and BOLD
      signal differences. Additionally, both data sets were integrated using an fMRI
      constrained source analysis. Finally, the results were compared with a previous
      study in which spatial instead of feature-based cueing was applied to an
      otherwise identical flanker task. Feature-based and spatial attention recruited a
      common fronto-parietal network during conflict processing. Irrespective of
      attention type (feature-based; spatial), this network responded to focussed
      attention (valid cueing) as well as context updating (invalid cueing), hinting at
      domain-general mechanisms. However, spatially and non-spatially directed
      attention also demonstrated domain-specific activation patterns for conflict
      processing that were observable in distinct EEG and fMRI data patterns as well as
      in the respective source analyses. Conflict-specific activity in visual brain
      regions was comparable between both attention types. We assume that the
      distinction between spatially and non-spatially directed attention types
      primarily applies to temporal differences (domain-specific dynamics) between
      signals originating in the same brain regions (domain-general localization).

PMID- 29371685
TI  - Extramedullary relapses after allogeneic stem cell transplantation for acute
      myeloid leukemia: clinical characteristics, incidence, risk factors and outcomes.
AB  - Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell
      transplant (allo-HCT) is challenging. Data on extramedullary relapse (EMR) after
      allo-HCT are limited. We analyzed 215 patients with AML who underwent allo-HCT in
      our institution between January 2005 and December 2015. We limited this
      retrospective review to patients who received a MA conditioning, were in complete
      remission (CR) at the time of transplant and who received a matched sibling
      transplant, all other patients were excluded to avoid heterogeneity. Seventy
      seven (35.8%) patients experienced disease relapse, 45 had BMR, and 32 had EMR.
      The only variable that was statistically associated with EMR post allo-HCT was
      male sex (OR = 3.2 (1.2, 8.2), p-value = 0.01); there was a trend for association
      between transplant in >CR2 and EMR (OR = 0.38 (0.14, 1.06), p-value = 0.06). The
      median overall survival (OS) after relapse for all relapses was 10 months (95% CI
      4.839-15.161). The median OS for BMR group was 8 months (95% CI 2.850-13.150) and
      14 months for the EMR group (95% CI 5.776-22.224); however, this was not
      statistically significant, p-value = 0.4. Multivariate analysis revealed that
      gender, treatment modality, and time from allo-HCT to relapse (>=12 vs. <12
      months) have significant association with the post-relapse death. Male gender was
      the only significant factor associated with EMR.

PMID- 29371686
TI  - Vedolizumab for treatment of steroid-refractory lower gastrointestinal acute
      graft-versus-host disease.

PMID- 29371683
TI  - DNA methylation of TOMM40-APOE-APOC2 in Alzheimer's disease.
AB  - The apolipoprotein E (APOE) epsilon4 allele is the major genetic risk factor for
      Alzheimer's disease (AD). Multiple regulatory elements, spanning the extended
      TOMM40-APOE-APOC2 region, regulate gene expression at this locus. Regulatory
      element DNA methylation changes occur under different environmental conditions,
      such as disease. Our group and others have described an APOE CpG island as
      hypomethylated in AD, compared to cognitively normal controls. However, little is
      known about methylation of the larger TOMM40-APOE-APOC2 region. The hypothesis of
      this investigation was that regulatory element methylation levels of the larger
      TOMM40-APOE-APOC2 region are associated with AD. The aim was to determine whether
      DNA methylation of the TOMM40-APOE-APOC2 region differs in AD compared to
      cognitively normal controls in post-mortem brain and peripheral blood. DNA was
      extracted from human brain (n = 12) and peripheral blood (n = 67). A methylation
      array was used for this analysis. Percent methylation within the TOMM40-APOE
      APOC2 region was evaluated for differences according to tissue type, disease
      state, AD-related biomarkers, and gene expression. Results from this exploratory
      analysis suggest that regulatory element methylation levels within the larger
      TOMM40-APOE-APOC2 gene region correlate with AD-related biomarkers and TOMM40 or
      APOE gene expression in AD.

PMID- 29371687
TI  - Role of up-front allogeneic hematopoietic stem cell transplantation for patients
      with aggressive adult T-cell leukemia-lymphoma: a decision analysis.

PMID- 29371688
TI  - PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance
      of Tregs in the skin.
AB  - Programmed cell death 1 ligand 1 (PD-L1) is a ligand of programmed cell death 1
      (PD-1) that functions as an immune checkpoint by down-regulating immune
      responses. To determine whether PD-L1 is a therapy target in vitiligo treatment,
      Pmel-1 vitiligo mice were treated with a PD-L1 fusion protein. Treatment with
      this fusion protein significantly reversed/suppressed depigmentation development
      in adult Pmel-1 mice. Mechanistically, enrichment of regulatory T cells (Treg) in
      the skin was detected after PD-L1 fusion protein treatment in Pmel-1 mice.
      Furthermore, Tregs abundance was also increased in both the spleen and
      circulation of Pmel-1 mice treated with PD-L1. These data indicate that PD-L1
      protein therapy inhibits the immune response and reverses depigmentation
      development in Pmel-1 vitiligo mice.

PMID- 29371690
TI  - Are dental students well-equipped to deal with difficult communication
      situations?

PMID- 29371689
TI  - Biologically active constituents of the secretome of human W8B2+ cardiac stem
      cells.
AB  - The benefits of adult stem cells for repair of the heart have been attributed to
      the repertoire of salutary paracrine activities they appear to exert. We
      previously isolated human W8B2+ cardiac stem cells (CSCs) and found they
      powerfully influence cardiomyocytes and endothelial cells to collectively promote
      cardiac repair and regeneration. Here, the complexity of the W8B2+ CSC secretomes
      was characterised and examined in more detail. Using ion exchange chromatography
      to separate soluble proteins based on their net surface charge, the secreted
      factors responsible for the pro-survival activity of W8B2+ CSCs were found within
      the low and medium cation fractions. In addition to the soluble proteins,
      extracellular vesicles generated from W8B2+ CSCs not only exhibited pro-survival
      and pro-angiogenic activities, but also promoted proliferation of neonatal
      cardiomyocytes. These extracellular vesicles contain a cargo of proteins, mRNA
      and primary microRNA precursors that are enriched in exosomes and are capable of
      modulating collectively many of the cellular pathways involved in protein
      metabolism, cell growth, as well as cellular responses to stress and organisation
      of the extracellular matrix. Thus the W8B2+ CSC secretome contains a multitude of
      bioactive paracrine factors we have now characterised, that might well be
      harnessed for therapeutic application for cardiac repair and regeneration.

PMID- 29371691
TI  - Surgical endodontics: are the guidelines being followed? A pilot survey.

PMID- 29371692
TI  - Severe headache following local anaesthesia in a patient with a history of
      traumatic brain injury - a case report.

PMID- 29371693
TI  - Perceived confidence and experience in oral surgery among final year
      undergraduate students in a UK dental school.

PMID- 29371694
TI  - A review of the indicator of sedation need (IOSN): what is it and how can it be
      improved?
AB  - The indicator of sedation need (IOSN) is a tool that has been devised to help
      with clinical decision-making, health needs assessment and commissioning purposes
      for the provision of sedation services. It can potentially increase access for
      patients to sedation when used as a screening tool, however, there are some
      shortcomings in the IOSN, such as the fact that it is not speciality specific,
      that can reduce its efficacy. As such, in its current form the IOSN may not be
      robust enough to be used as a sole commissioning tool and may in fact create
      barriers to patients that would benefit from sedation. By addressing these issues
      and understanding its limitations, the IOSN can be used more effectively for its
      intended purposes.

PMID- 29371695
TI  - Metformin ameliorates experimental-obesity-associated autoimmune arthritis by
      inducing FGF21 expression and brown adipocyte differentiation.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease involving excessive
      inflammation. Recently, RA associated with a metabolic disorder was revealed to
      be non-responsive to RA medications. Metformin has been reported to have a
      therapeutic effect on RA and obesity. The aim of this investigation was to study
      the therapeutic effect and the underlying mechanism of metformin's action in an
      experimental model of collagen-induced arthritis (CIA) associated with obesity.
      Metformin was administered daily for 13 weeks to mice with CIA that had been fed
      a high-fat diet. Metformin ameliorated the development of CIA in obese mice by
      reducing autoantibody expression and joint inflammation. Furthermore, metformin
      decreased the expression levels of pSTAT3 and pmTOR and had a small normalizing
      effect on the metabolic profile of obese CIA mice. In addition, metformin
      increased the production of pAMPK and FGF21. Metformin also induced the
      differentiation of brown adipose tissue (BAT), which led to a reciprocal balance
      between T helper (Th) 17 and regulatory T (Treg) cells in vitro and in vivo.
      These results suggest that metformin can dampen the development of CIA in obese
      mice and reduce metabolic dysfunction by inducing BAT differentiation. Thus,
      metformin could be a therapeutic candidate for non-responsive RA.

PMID- 29371696
TI  - Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via
      MyD88's effects on the gut microbiota.
AB  - Although radiation therapy is a cornerstone of modern management of malignancies,
      various side effects are inevitably linked to abdominal and pelvic cancer after
      radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life
      quality of cancer survivors and even shortens their lifespan. Hydrogen has been
      shown to protect against tissue injuries caused by oxidative stress and excessive
      inflammation, but its effect on radiation-induced intestinal injury was
      previously unknown. In the present study, we found that oral gavage with hydrogen
      water increased the survival rate and body weight of mice exposed to total
      abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated
      with an improvement in GI tract function and the epithelial integrity of the
      small intestine. Mechanistically, microarray analysis revealed that hydrogen
      water administration upregulated miR-1968-5p levels, thus resulting in parallel
      downregulation of MyD88 expression in the small intestine after TAI exposure.
      Additionally, high-throughput sequencing showed that hydrogen-water oral gavage
      resulted in retention of the TAI-shifted intestinal bacterial composition in
      mice. Collectively, our findings suggested that hydrogen-water might be used as a
      potential therapeutic to alleviate intestinal injury induced by radiotherapy for
      abdominal and pelvic cancer in preclinical settings.

PMID- 29371697
TI  - RNF138-mediated ubiquitination of rpS3 is required for resistance of glioblastoma
      cells to radiation-induced apoptosis.
AB  - An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or
      macrophage migration inhibitory factor in non-small-cell lung cancer is
      responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM)
      has not been investigated to date. Here we found that in irradiated GBM cells,
      rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring
      finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently
      led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we
      analyzed the interactome of rpS3 in DeltaRNF138 GBM cells. Nuclear rpS3
      interacted with DNA damage inducible transcript 3 (DDIT3), leading to DDIT3
      induced apoptosis in irradiated DeltaRNF138 GBM cells. These results were
      confirmed using in vivo orthotopic xenograft models and GBM patient tissues. This
      study aims to clarify the role of RNF138 in GBM cells and demonstrate that rpS3
      may be a promising substrate of RNF138 for the induction of GBM radioresistance,
      indicating RNF138 as a potential target for GBM therapy.

PMID- 29371698
TI  - Rab25 augments cancer cell invasiveness through a beta1 integrin/EGFR/VEGF
      A/Snail signaling axis and expression of fascin.
AB  - The small GTP-binding protein Rab25 is associated with tumor formation and
      progression. However, recent studies have shown discordant effects of Rab25 on
      cancer cell progression depending on cell lineage. In the present study, we
      elucidate the underlying mechanisms by which Rab25 induces cellular invasion. We
      demonstrate that Rab25 increases beta1 integrin levels and subsequent activation
      of EGFR and upregulation of VEGF-A expression, leading to increased Snail
      expression, epithelial-to-mesenchymal transition and cancer cell invasiveness.
      Strikingly, we identify that Snail mediates Rab25-induced cancer cell
      invasiveness through fascin expression and that ectopic expression of Rab25
      aggravates metastasis of ovarian cancer cells to the lung. We thus demonstrate a
      novel role of a beta1 integrin/EGFR/VEGF-A/Snail signaling cascade in Rab25
      induced cancer cell aggressiveness through induction of fascin expression, thus
      providing novel biomarkers and potential therapeutic targets for Rab25-expressing
      cancer cells.

PMID- 29371701
TI  - Interventions for pressure ulcers: a summary of evidence for prevention and
      treatment.
AB  - STUDY DESIGN: Narrative review. OBJECTIVES: Pressure ulcers are a common
      complication in people with reduced sensation and limited mobility, occurring
      frequently in those who have sustained spinal cord injury. This narrative review
      summarises the evidence relating to interventions for the prevention and
      treatment of pressure ulcers, in particular from Cochrane systematic reviews. It
      also aims to highlight the degree to which people with spinal cord injury have
      been included as participants in randomised controlled trials included in
      Cochrane reviews of such interventions. SETTING: Global. METHODS: The Cochrane
      library (up to July 2017) was searched for systematic reviews of any type of
      intervention for the prevention or treatment of pressure ulcers. A search of
      PubMed (up to July 2017) was undertaken to identify other systematic reviews and
      additional published trial reports of interventions for pressure ulcer prevention
      and treatment. RESULTS: The searches revealed 38 published systematic reviews (27
      Cochrane and 11 others) and 6 additional published trial reports. An array of
      interventions is available for clinical use, but few have been evaluated
      adequately in people with SCI. CONCLUSIONS: The effects of most interventions for
      preventing and treating pressure ulcers in people with spinal cord injury are
      highly uncertain. Existing evaluations of pressure ulcer interventions include
      very few participants with spinal cord injury. Subsequently, there is still a
      need for high-quality randomised trials of such interventions in this patient
      population.

PMID- 29371700
TI  - Intra-rater and inter-rater reliability of the Penn Spasm Frequency Scale in
      People with chronic traumatic spinal cord injury.
AB  - STUDY DESIGN: Psychometric study. OBJECTIVES: Evaluate the intra-rater and inter
      rater reliability of the Penn Spasm Frequency Scale (PSFS) in people with chronic
      traumatic spinal cord injury (SCI). SETTING: Community setting. METHODS:
      Participants with chronic traumatic SCI were administered the PSFS, a self
      reported spasticity measure in which the individual documents the frequency (Part
      1) and severity (Part 2) of their muscle spasms. One rater administered the PSFS
      at baseline, 5 to 10 days, and 4 to 6 weeks after baseline. The second rater
      administered the PSFS within 3 days of the first rater. RESULTS: Reliability was
      assessed using weighted-kappa (95% confidence interval) statistics. In 61
      participants, the intra-rater reliability between 5 to 10 days and 4 to 6 weeks
      after baseline was 0.822 (0.709, 0.935) and 0.734 (0.586, 0.883), respectively,
      for PSFS Part 1. With the addition of Part 2, the intra-rater reliabilities were
      0.812 (0.705, 0.919) and 0.729 (0.586, 0.872) for 5 to 10 days and 4 to 6 weeks,
      respectively. The PSFS inter-rater reliability within a 3-day time interval was
      0.862 (0.759, 0.965) for Part 1 and 0.857 (0.762, 0.952) with the addition of
      Part 2. CONCLUSIONS: PSFS Part 1 intra-rater and inter-rater reliability weighted
      kappa statistics are in the "almost perfect" category, with lower confidence
      bounds in the "substantial" range. By adding Part 2 the reliability decreases,
      but the kappa statistics remain "substantial," with a lower confidence bound in
      the "moderate" range. The PSFS is probably a reliable outcome measure to assess
      self-reported spasticity after chronic traumatic SCI.

PMID- 29371703
TI  - Mitochondrial DNA selection in human germ cells.

PMID- 29371699
TI  - Identification of a biosynthetic gene cluster for the polyene macrolactam
      sceliphrolactam in a Streptomyces strain isolated from mangrove sediment.
AB  - Streptomyces are a genus of Actinobacteria capable of producing structurally
      diverse natural products. Here we report the isolation and characterization of a
      biosynthetically talented Streptomyces (Streptomyces sp. SD85) from tropical
      mangrove sediments. Whole-genome sequencing revealed that Streptomyces sp. SD85
      harbors at least 52 biosynthetic gene clusters (BGCs), which constitute 21.2% of
      the 8.6-Mb genome. When cultivated under lab conditions, Streptomyces sp. SD85
      produces sceliphrolactam, a 26-membered polyene macrolactam with unknown
      biosynthetic origin. Genome mining yielded a putative sceliphrolactam BGC (sce)
      that encodes a type I modular polyketide synthase (PKS) system, several beta
      amino acid starter biosynthetic enzymes, transporters, and transcriptional
      regulators. Using the CRISPR/Cas9-based gene knockout method, we demonstrated
      that the sce BGC is essential for sceliphrolactam biosynthesis. Unexpectedly, the
      PKS system encoded by sce is short of one module required for assembling the 26
      membered macrolactam skeleton according to the collinearity rule. With
      experimental data disfavoring the involvement of a trans-PKS module, the
      biosynthesis of sceliphrolactam seems to be best rationalized by invoking a
      mechanism whereby the PKS system employs an iterative module to catalyze two
      successive chain extensions with different outcomes. The potential violation of
      the collinearity rule makes the mechanism distinct from those of other polyene
      macrolactams.

PMID- 29371704
TI  - Means and myths of mentoring.

PMID- 29371705
TI  - Exonuclease EXD2 in mitochondrial translation.

PMID- 29371706
TI  - Hitchhiking on selective autophagy.

PMID- 29371707
TI  - Illuminating MSK1's role in tumour dormancy.

PMID- 29371708
TI  - Diabetic Neuropathy - situational analysis in Pakistan.

PMID- 29371709
TI  - Association of single nucleotide polymorphism in CD28(C/T-I3 + 17) and CD40 (C/T
      1) genes with the Graves' disease.
AB  - OBJECTIVE: To find out a correlation between the single nucleotide polymorphisms
      in cluster of differentiation 28 and cluster of differentiation 40 genes with
      Graves' disease, if any. METHODS: This case-control study was conducted at the
      Multan Institute of Nuclear Medicine and Radiotherapy, Multan, Pakistan, and
      comprised blood samples of Graves' disease patients and controls. Various risk
      factors were also correlated either with the genotype at each single-nucleotide
      polymorphism or with various combinations of genotypes studied during present
      investigation. RESULTS: Of the 160 samples, there were 80(50%) each from patients
      and controls. Risk factor analysis revealed that gender (p=0.008), marital status
      (p<0.001), education (p<0.001), smoking (p<0.001), tri-iodothyronine (P <0.001),
      thyroxin (p<0.001) and thyroid-stimulating hormone (p<0.000) levels in blood were
      associated with Graves' disease. CONCLUSIONS: Both single-nucleotide
      polymorphisms in both genes were not associated with Graves' disease, either
      individually or in any combined form.

PMID- 29371710
TI  - Clinical presentations and outcomes of the children with tuberculous meningitis:
      An experience at a tertiary care hospital.
AB  - OBJECTIVE: To determine the clinical presentations and outcomes of the children
      suffering from tuberculous meningitis. METHODS: This prospective, descriptive
      study was conducted at the Children's Hospital and the Institute of Child Health,
      Multan, Pakistan, from February to December 2015. The Pakistan Paediatric
      Association scoring chart for tuberculosis was used as a tool for the probable
      diagnosis. The clinical symptoms with their durations were noted. Clinical stages
      of tuberculous meningitis, cerebrospinal fluid analysis and computerised
      tomography brain findings were noted for each patient. The outcomes in the form
      of death or neurological disabilities at the time of hospital discharge were
      noted. SPSS 19 was used for data analysis. RESULTS: Of the 40 participants,
      25(62.5%) were males and 15(37.5%) were females. The mean age of the patients was
      4.24+/-3.32 years. Besides, 26(65%) patients were less than 5 years of age. All
      the patients (100%) were categorised as stage 3 tuberculous meningitis. The
      history of prolonged duration of fever 39(97.55%) and altered level of sensorium
      40(100%) were the most common clinical presentations. Moreover, 2(5%) patients
      died during this study. All the 38(95%) survivors had neurological disabilities.
      There were motor deficits in 37(97.4%) patients, altered level of sensorium in
      35(92%), cranial nerve palsies in 9(23.5%), epilepsy in 29(76.3%) and
      hydrocephalus in 32(84%) patients. CONCLUSIONS: The children were the most
      vulnerable group for the worst form of tuberculous meningitis and had a grave
      outcome.

PMID- 29371711
TI  - Achilles tendon elasticity decreases with intermittent claudication in patients
      by Acoustic Radiation Force Impulse Imaging (ARFI).
AB  - OBJECTIVE: To investigate the value of Acoustic Radiation Force Impulse
      elastography and its application in Achilles tendon elasticity of intermittent
      claudication due to lower extremity arterial ischaemia. METHODS: This prospective
      case-control study was conducted at the Department of Radiology, Faculty of
      Medicine, Baskent University, Istanbul, Turkey, from October 2015 to January
      2016, and comprised bilateral Achilles tendons of patients with intermittent
      claudication and healthy individuals. Shear-Wave Velocity (SWV) of each tendon
      was measured using Acoustic Radiation Force Impulse elastography. Arterial
      Doppler ultrasonography at tibialis posterior artery was performed to establish
      the diagnosis of occlusive arterial disease, and the degree of obstruction was
      recorded. SPSS 16 was used for data analysis. RESULTS: Of the 84 subjects,
      42(50%) were patients and 42(50%) were controls. The number of bilateral Achilles
      tendons was 168, i.e. 84(50%) of patients and 84(50%) of controls. SWV of the
      Achilles tendon were different between the two groups (p<0.05). The mean SWV was
      5.24+/-0.45 m/s in the relaxed state in the patients and 2.83+/-0.56 m/s in the
      controls. No monophasic flow pattern was observed in 23(54.8%) posterior tibial
      artery and SWV was 4.94+/-0.40 m/s in the relaxed state Achilles tendon in
      patients. Monophasic flow pattern was observed in 61(72.6%) posterior tibial
      artery and SWV was 5.35+/-0.42 m/s in the relaxed state Achilles tendon in
      patients. SWV values were higher in monophasic flow patterns in the posterior
      tibial artery than in those without monophasic flow patterns in patients group
      (p<0.01). CONCLUSIONS: The elasticity of healthy tendon decreased with
      intermittent claudication in patients.

PMID- 29371712
TI  - Complement factor 3 among children with hepatitis A: Assessment of bilirubin
      levels.
AB  - OBJECTIVE: To evaluate the complement factor 3 levels in children with hepatitis
      A. METHODS: This observational study was conducted at the Infectious Diseases
      Hospital of Hotan District, China, from September 2014 to January 2015, and
      comprised children with hepatitis A and controls. The patients were divided into
      two groups. The ones with total bilirubin less than or equal to 2mg/dl comprised
      group A, while the ones whose total bilirubin was more than 2mg/dl was named
      group B. Besides, we enrolled age- and gender-matched healthy children as
      controls. SPSS 13 was used for data analysis. RESULTS: Of the 100 participants,
      41(41%) were in group A, 29(29%) in group B and 30(30%) were controls. The serum
      level of alanine aminotransferase, aspartate aminotransferase, total bile acid,
      the incidence of ascites and the incidence of hepatic encephalopathy were
      significantly increased in patients of group B when compared to group A (p=0.046,
      p=0.009, p<0.0001, p=0.018 and p=0.026). The levels of prothrombin time activity,
      total protein and albumin were higher in group A (p<0.0001, p<0.0001, and p
      <0.0001). Total hepatitis A patients had significantly lower serum complement
      factor 3 levels compared to normal controls (p =0.018). Group B had significantly
      lower serum complement factor 3 levels compared to normal controls (p <0.0001)
      and group A (p<0.0001). In total patients, complement factor 3 levels were
      negatively correlated with total bilirubin and alanine aminotransferase
      (p=0.029), while complement factor 3 levels were positively correlated with
      prothrombin time activity (p=0.001). CONCLUSIONS: Complement factor 3 values were
      found to be decreased in children hospitalised with hyperbilirubinaemia hepatitis
      A.

PMID- 29371713
TI  - Frequency of underweight and stunting among children entering school in a small
      urban locality and their association with academic performance.
AB  - OBJECTIVE: To determine the frequency of underweight and stunting among the
      children entering first year of school and to assess its associated factors.
      METHODS: This descriptive, analytical study was conducted at 5 schools of Rabwah,
      Pakistan, from August to September 2015, and comprised all students who got
      admission in the selected schools during the study period. Name, father's name,
      gender, weight, height, status of height, and weight on Z-score charts, and marks
      obtained in the test were recorded. SPSS 20 was used for statistical analysis.
      RESULTS: Of the 478 participants, 212(44.4%) were boys and 266(55.6%) were girls.
      The overall mean age was 66.6+/-5.966 months (range: 41-129 months). Overall,
      53(11.1%) were underweight, 22(4.6%) were severely underweight, 55(11.5%) had
      stunting and 12(2.5%) had severe stunting. Median marks (Interquartile Range
      [IQR]) in admission test for obese, overweight, normal, underweight and severely
      underweight children were 76.3%(37.2-84.7), 65.9%, 66.7%(56.4-72.3), 64.6%(47
      71), and 67%(55.3-78), respectively. Median marks (IQR) in admission test for
      tall, normal height, stunted and severe stunted children were 24.1%, 67%(57.3
      73), 57%(31.1-67.8), and 62.6%(49.7-68.3), respectively. Children with stunting
      scored significantly fewer marks compared to children of normal height (p<0.05).
      CONCLUSIONS: Stunting and underweight were common problems among children
      starting school. Stunting was found to be associated with lower marks in
      admission test.

PMID- 29371714
TI  - Diagnostic validation of rapid molecular detection of Mycobacterium tuberculosis
      in pus samples by GeneXpert.
AB  - OBJECTIVE: To evaluate the performance of GeneXpert for detection of
      mycobacterium tuberculosis in pus samples and compare its results with
      conventional techniques in terms of validity, rapidity and rifampicin resistance.
      METHODS: This longitudinal, descriptive study was conducted at Jinnah Hospital,
      Lahore, Pakistan, from January 2012 to December 2015, and comprised pus samples
      of people suspected of having extra-pulmonary tuberculosis. Participants were
      included by using consecutive sampling technique. The pus samples were subjected
      to Ziehl-Neelsen smear microscopy and Lowenstein-Jensen culture as per World
      Health Organisation's protocol and GeneXpert as per manufacturer protocol. SPSS
      17 was used for data analysis. Validity of GeneXpert and rifampicin resistance
      were determined and compared with Ziehl-Neelsen staining using Lowenstein-Jensen
      culture as the gold standard. RESULTS: Of the 212 pus samples, 84(39.6%) were
      positive on Lowenstein-Jensen culture with mean turnaround time of 20+/-6 days,
      77(36.3%) on GeneXpert and 22(10.4%) on Ziehl-Neelsen smear. The highest
      detection rate of mycobacterium tuberculosis 62(80.5%) was in lymph node samples
      by GeneXpert. The sensitivity and specificity of GeneXpert were 91.6% and 100%
      respectively, while Ziehl-Neelsen smear showed a sensitivity26.2% and specificity
      of 100%. Rifampicin resistance was detected in 5(6.4%) pus samples by GeneXpert.
      CONCLUSIONS: GeneXpert had a higher validity compared to Ziehl-Neelsen smear
      microscopy.

PMID- 29371715
TI  - Relationship between hydrocephalus etiology and ventriculoperitoneal shunt
      infection in children and review of literature.
AB  - OBJECTIVE: The purpose of this retrospective study was to clarify the
      relationship of shunt infection to childhood hydrocephalus etiology. METHODS: We
      analyzed 1021 patients with childhood hydrocephalus who underwent V-P shunting
      over a period of approximately 15 years. The etiology of 1021 patients include
      myelomeningocele (794 patient), congenital (165 patient) and intraventricular
      haemorrhage (62 patient). RESULTS: Of the 1021 patients who underwent V-P
      shunting, 19.32% exhibited shunt infection. Shunt infection developed in 180
      (22.67%) of 794 patients with myelomeningocele, 9 (5.45%) of 165 patients with
      congenital obstructive hydrocephalus, and 9 (14.51%) of 62 patients with
      intraventricular haemorrhage. Recurrent shunt infection was detected in 54
      (27.27%) of 198 patients with a previous shunt infection. CONCLUSIONS: Patients
      with previous shunt infection as well as those with shunts associated with
      myelomeningocele were observed to be at a greater risk for shunt infection.
      Results indicated that patients with congenital obstructive hydrocephalus may be
      less prone to shunt infections.

PMID- 29371716
TI  - High incidence of malaria along the Pak-Afghan bordering area.
AB  - OBJECTIVE: To check the epidemiology of malaria along Pak-Afghan bordering area..
      METHODS: The prospective study was conducted at Hatmi Medical Centre, Barmal
      district, Afghanistan, from March 2014 to February 2016, and comprised patients
      living in bordering areas between Pakistan's North Waziristan Agency and
      Afghanistan's Paktika province. Blood samples were collected from subjects with
      symptoms of malaria for plasmodium microscopy in Giemsa-stained thick and thin
      film. Slides were stored in a secure slide box and were reconfirmed by microscopy
      expert at the Department of Pathology, Gomal Medical College, Dera Ismail Khan,
      Pakistan. SPSS 19 was used for data analysis. RESULTS: Of the total 3,840
      patients, 2,655(69.1%) tested negative for malaria while the remaining
      1,185(30.9%) tested positive - of whom 788(66.5%) were males and 397(33.5%) were
      females. Of the positive cases, positive, 1,074(90.6%) were Plasmodium vivax,
      76(6.4%) Plasmodium falciparum and 35(3%) were mixed species infections with no
      case of Plasmodium ovale and Plasmodium malariae. CONCLUSIONS: Strict malaria
      control measures are needed in both countries.

PMID- 29371717
TI  - Symptom management in Behcets disease.
AB  - OBJECTIVE: To determine the symptoms experienced by patients diagnosed with
      Behcet's Disease and how they cope with them. METHODS: The qualitative study was
      conducted from September 2013 to March 2014 at Ege University Medical Faculty
      Hospital, Turkey, comprising patients having all symptoms of Behcet's Disease.
      Data was collected through semi-structured focus-group interview form. The
      findings were assessed using Theory of Unpleasant Symptoms and Symptom Management
      Theory. SPSS 20 and Nvivo 10 were used for data analysis. RESULTS: Of the 35
      patients, 16(45.8%) were female and 19(54.2%) were male. The symptoms affected
      patients' lives, and the patients used either positive or negative symptom
      management strategies, leading to either positive or negative results during
      symptom management. CONCLUSIONS: Behcet's Disease patients needed effective
      symptom management.

PMID- 29371718
TI  - Frequency of carrier screening and preventive orientation among first degree
      relatives of Thalassaemia patients.
AB  - OBJECTIVE: To get preliminary data regarding the prevention of thalassaemia major
      in future generations. METHODS: This Knowledge Attitude Practices study was
      conducted at Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from
      January to June 2016, using non-probability purposive sampling. Parents of
      children undergoing transfusion were interviewed. Questionnaires were used to
      collect demographics and data about awareness, attitude and frequency of
      screening among the first degree relatives of a thalassaemia major patient. SPSS
      20 was used for data analysis. RESULTS: Of the 270 respondents 240(88.9%) had
      utilised screening services for their asymptomatic children and had a positive
      attitude towards prevention, but 30(11.1%) families did not screen asymptomatic
      children for thalassaemia minor. Besides, 49(18.1%) families had more than one
      thalassaemia major child in their nuclear family, while, 3(1.1%) were unwilling
      to let their children undergo tests. Nine (3.3%) respondents said they will not
      ask a prospective daughter/son-in-law to get tested for thalassaemia minor, while
      194(71.9%) respondents had had cousin marriages. CONCLUSIONS: There were
      significant gaps in awareness among affected families.

PMID- 29371719
TI  - Awareness of risk factors and fallacies associated with urinary bladder cancer in
      our population: A prospective survey.
AB  - OBJECTIVE: To determine the awareness of risk factors for bladder cancer and
      false beliefs associated with this disease. METHODS: This cross-sectional study
      was conducted at the Kidney Centre, Karachi, from January to February 2015, and
      comprised subjects who presented to the various in-house clinics. The subjects
      were interviewed using a questionnaire comprising demographic parameters, level
      of education and awareness of smoking hazards, knowledge and false beliefs
      associated with bladder cancer. A pilot study was performed prior to the main
      study and the questionnaire was redesigned accordingly. SPSS 20 was used for data
      analysis. RESULTS: Of the 1,000 respondents, 593(59.3%) were males and 407(40.7%)
      were females. Moreover, 229(22.9%) respondents were aware of the association
      between smoking and bladder cancer compared to 858(85.8%) who knew that there is
      an association between smoking and lung cancer. Besides, 479(47.9%) respondents
      said that smoking caused tuberculosis. Patients with a higher level of education
      were statistically more likely to be aware of the association between smoking and
      bladder cancer, i.e. 91(9.1%) uneducated, 208(20.8%) primary, 182(18.2%)
      secondary, 222(22.2%) intermediate and 352(35.2%) graduates (p=0.0001). Most
      common fallacy associated with bladder cancer was low intake of water 504(50.4%),
      followed by multiple sexual partners 362(36.2%). CONCLUSIONS: Most patients were
      unaware of the relationship between bladder cancer and tobacco smoking.

PMID- 29371720
TI  - Learning preferences among dental students using the VARK questionnaire: A
      comparison between different academic levels and gender.
AB  - OBJECTIVE: To examine the learning style preferences of undergraduate dental
      students and determine the influence of gender on their selection. METHODS: This
      descriptive, cross-sectional study was conducted at the College of Dentistry,
      King Saud University, in Riyadh, Saudi Arabia, from September 2016 to January
      2017.The Arabic version of visual, audio, read/write, and kinaesthetic
      questionnaire was administered to students from the first to the fifth academic
      year. Data was analysed using SPSS 21. P<0.05 was considered significant.
      RESULTS: Of the 491 students, 368(75.1%) completed the questionnaire. Of them,
      269(73.1%) were males and 99(26.9%) were females. Significant differences were
      found when learning styles were compared (p<0.05). No significant differences
      could be found when the models were assessed as in the unimodal, bimodal,
      trimodal or quadmodal methods (p>0.05). A significant difference was found
      between genders when learning styles were compared (p=0.05). Males preferred the
      unimodal style, while females preferred the bimodal and quadmodal styles almost
      equally (p<0.05). CONCLUSIONS: Most dental undergraduate students preferred multi
      modal learning.

PMID- 29371721
TI  - Knowledge and attitude of blood donation among female medical students in
      Faisalabad.
AB  - OBJECTIVE: To assess the knowledge, practices and attitude of medical students
      towards blood donation. METHODS: This cross-sectional study was conducted at the
      University of Faisalabad, Faisalabad, Pakistan, from April to August 2016, and
      comprised female medical students. Multi-stage sampling technique was employed. A
      structured questionnaire was included as data-collection tool. Statistical
      analysis was done using SPSS 20. RESULTS: Of the 500 students, 469(93.8%)
      responded to the questionnaire. Of them, 419(89.3%) females had never donated
      blood and only 2(0.4%) were regular voluntary donors. The best source from which
      the participants heard about blood donation was friends 259(55.2%). When coming
      to reasons for not donating blood, there was significant association of many
      factors like fear (p <0.001), the collection facility being far from the place (p
      <0.001), not having enough time to donate (p <0.001). Of the 50(10.7%)
      respondents who had ever donated blood, 48(96%) said the main motivator was
      saving lives of the people. CONCLUSIONS: Female medical students were aware of
      the basic knowledge about blood donation.

PMID- 29371723
TI  - Outcomes of cataract surgery at teaching hospital in Karachi.
AB  - OBJECTIVE: To assess outcomes of cataract surgery at a tertiary care hospital in
      Karachi. METHODS: This retrospective study was conducted at Aga Khan University
      Hospital, Karachi, and comprised data of patients who underwent cataract surgery
      from January 2011 to December 2015. The data was collected using guidelines based
      on World Health Organisation systems for quality monitoring. Postoperative follow
      up was done at 1 day, 1 week, 4 weeks and after 12 weeks. Visual acuity was
      recorded as good (6/6-6/18), borderline (6/18-6/60) and poor (<6/60).
      Intraoperative and postoperative complications were also noted. RESULTS: Of the
      570 patient charts reviewed, 527(92.45%) were included in the study. Among them,
      302(57.4%) were females and 225(42.6%) were males. The overall mean age of
      patients was 59.8+/-7.2 years. There were 275(52.2%) right eyes, 382(72.5%) were
      myope and the remaining 145(27.5%) were hypermetrope. There were 315(59.6%)
      patients who suffered from different systemic diseases, with diabetes mellitus
      being on the top of list followed by hypertension. Pre-operative best corrected
      visual acuity was good in 35(6.7%) patients, borderline in 355(67.4%), and poor
      in 137(25.9%). CONCLUSIONS: The surgical outcomes were comparable with previous
      studies.

PMID- 29371722
TI  - Physiotherapy and pharmacy students perception of educational environment in a
      medical university from Pakistan.
AB  - OBJECTIVE: To assess and compare the perceptions of the educational environment
      between physiotherapy and pharmacy students in a public-sector medical
      university. METHODS: This cross-sectional study was conducted at the Peoples
      University of Medical and Health Sciences for Women, Nawabshah, Pakistan, and
      comprised undergraduate physiotherapy and pharmacy students. The Dundee Ready
      Educational Environment Measure questionnaire was used to assess the perceptions
      of students about their educational environment. Global and subscale scores were
      computed and compared between the respondents. P<0.05 was considered
      statistically significant. RESULTS: Of the 300 questionnaires, 281(93.66%) were
      returned duly filled in. The overall mean global score was 127.2+/-16.0. For
      physiotherapy students, the mean global score was 124.9+/-14.0 while it was
      131.7+/-18.9 for pharmacy students (p=0.16). The domain scores were comparable
      for both specialties (p>0.05). There was no significance difference in the global
      and domain scores for preclinical and clinical years in the students (p>0.05).
      However, in the physiotherapy students, the global and domain scores for Dundee
      Ready Educational Environment Measure were significantly lower in clinical than
      preclinical students (p<0.05) except for students' social self-perception
      (p>0.05). CONCLUSIONS: Students were overall positive about their educational
      environment.

PMID- 29371724
TI  - How close are we? An audit of biometry of a tertiary care hospital in Karachi.
AB  - OBJECTIVE: To evaluate the accuracy of biometry in the post-op phase of cataract
      surgery. METHODS: This study was conducted at Liaquat National Hospital, Karachi,
      from June 2015 to July 2016, and comprised the audit of patients who underwent
      cataract surgery during the period. Keratometry was done on Haag-Strait manual
      keratometer and A-scan was done by applanation contact method on SonoMed machine.
      Theoretic-T formula was used to calculate desired intraocular lens power for all
      kinds of axial lengths. A single surgeon operated upon the same Alcon
      Constellation phacoemulsification machine. Postoperative follow-up was done by
      monitoring auto refraction and visual acuity on days 1, 7, 30 and 90. SPSS 21 was
      used for data analysis.. RESULTS: Of 244 patients, 121(49.60%) were males and
      123(50.40%) were females. There were 123(50.40%) right eyes and 121(49.60%) left
      eyes. Overall, 132(54.10%) achieved postoperative refraction within +/-0.5 D of
      target and 193(79.10%) within +/-1 D of target. Age, gender and laterality had no
      significant effect on outcomes (p>0.05 each). CONCLUSIONS: Postoperative
      refraction corresponded quite closely with global recommendations.

PMID- 29371725
TI  - Diabetic neuropathy and painful diabetic neuropathy: Cinderella complications in
      South East Asia.
AB  - The most common and debilitating microvascular complication of diabetes is
      diabetic peripheral neuropathy (DPN), affecting 50-90% of people with diabetes.
      The major manifestations of DPN are painful (pDPN) and painless diabetic
      peripheral neuropathy. Painful symptoms, occur in the feet and are worse at night
      and whilst they alert both the patient and physician, are often misdiagnosed and
      mismanaged. The devastating presentation of painless neuropathy with loss of
      sensation is foot ulceration and Charcot foot. The explosion of diabetes,
      especially in the South East Asian (SEA) region will result in an increasing
      prevalence of both painful and painless diabetic peripheral neuropathy. PubMed,
      EMBASE, Medline and Google Scholar databases were searched between 1990 and 2017.
      This highlights the widely varying prevalence of DPN and pDPN in the World Health
      Organization (WHO) defined SEA countries and the dearth of published studies,
      especially in pDPN. We believe this will provide new direction for future
      research on DPN in the SEA region.

PMID- 29371726
TI  - Association of arg16gly and gln27glu, b2-adrenergic receptor gene polymorphism
      with asthma. A systematic review and meta-analysis of case control studies.
AB  - The study was planned to assimilate quantitatively the available evidences on
      association of Arg16Gly and Glu27Gln with asthma and to produce more precise
      results. All case-control studies conducted on adults were searched on Medline,
      Embase, PubMed, Wiley online library according to Preferred Reporting Items for
      Systematic Review and Meta-Analysis guidelines. The strength of association was
      measured by odds ratios with 95% confidence interval. A total of 17 case-control
      studies were included in the meta-analysis and there was no significant
      association of asthma with Arg16Gly (odds ratio = 1.19; 95% confidence interval =
      0.75-1.50, p=0.459) and Glu27Gln of ADRb2 polymorphism (odds ratio=0.87, 95%
      confidence interval =0.44-1.71, p=0.683). Moreover, neither Gly16 allele (odds
      ratio = 0.98; 95% confidence interval = 0.70-1.38, p=0.867) nor Glu27 allele
      (odds ratio = 0.67, 95% confidence interval = 0.38-1.19, p=0.169) contributed to
      asthma susceptibility. There was also no significant association between
      haplotypes of both single nucleotide polymorphisms and asthma (p>0.05). Data
      indicated that adrenergic receptor b2 did not contribute markedly to
      susceptibility to asthma (p>0.05).

PMID- 29371727
TI  - Role of multi-parametric (mp) MRI in prostate cancer.
AB  - Multi-parametric magnetic resonance imaging is increasingly being recommended as
      standard imaging modality for prostate cancer diagnosis and staging. It comprises
      structural T2 and T1 sequences supplemented by functional imaging techniques,
      i.e. diffusion-weighted, dynamic contrast enhanced and spectroscopic imaging. Pre
      biopsy multi-parametric magnetic resonance imaging is recommended for both
      detection and staging as it avoids biopsy artefact, and when normal, has a
      negative predictive value of 95% for significant cancer. Magnetic resonance
      imaging-guided prostate biopsy targets only area(s) considered to be suspicious
      for prostate cancer, hence resulting in improved accuracy. Dynamic contrast
      enhancing helps in the detection of cancer and for the assessment of extra
      capsular extension, distal urethral sphincter and seminal vesicles involvement.
      The role of multi-parametric magnetic resonance imaging in follow-up of patients
      on active surveillance is also increasingly recognised. Its role is now further
      expanded to facilitate targeted therapies. This review focuses on the evolving
      role of multi-parametric magnetic resonance imaging in diagnosis and management
      of prostate cancer.

PMID- 29371728
TI  - Spatial distribution of road traffic crash fatalities in Karachi: Perspective
      from 2008-2012.
AB  - Road Traffic Crash (RTC) mortality and morbidity is one of the major public
      health problems in Karachi. In this study we used geographic information systems
      (GIS) to visualize and quantify the spatial distribution of RTC mortality and
      yearly trend from 2008 to 2012, for all 24 administrative subdivisions of
      Karachi, using Road Traffic Injury Research and Prevention Center's (RTIRPC)
      data. Cumulatively, 6040 deaths were recorded by RTIRPC, out of which we were
      able to map 4657 (77.1%) deaths based on location information available in the
      database. During the 5-year period, highest number of cumulative RTC fatalities
      were recorded for Kemari, Bin Qasim, and Gushan-e-Iqbal; while lowest were
      recorded in Malir, Orangi, Korangi Cantonment, and Karachi Cantonment. Use of GIS
      for studying spatial distribution of RTC would help craft better response to RTC
      in the city and design public policy.

PMID- 29371729
TI  - Co-morbid depression in individuals with type 2 diabetes mellitus.
AB  - It was a descriptive cross-sectional study conducted to determine the frequency
      of depression and association with factors in type 2 diabetics in diabetic clinic
      of Fauji Foundation Hospital Rawalpindi from 1st January - 30th June 2014. In all
      110 diabetic patients were selected using convenient Sampling. Data was collected
      by using a pre- tested structured proforma. Beck's Depression Inventory (BDI)
      scale was used to screen depression. There were 20 males (18.2%) and 90 females
      (81.8%) in this study. Females had more mood disturbances and depression as
      compared to males, however difference was not statistically significant
      (p<0.769). 28.2% individuals had mild mood disturbances, while borderline
      clinical depression was present in 23.6% of study group, 20.9% were having
      moderate depression and 9.1% were having severe depression, rest 1.2% had extreme
      depression. Overall 55.5% respondents had depression in this study. Obesity was
      present in 60% of diabetics, 62.7% were hypertensives and 26.4% had ischaemic
      heart disease. Depression was statistically significantly associated with
      hypertension (p< 0.002).

PMID- 29371730
TI  - Nurses interventions to reduce unwanted noise.
AB  - The study evaluated the nurses' interventions to reduce unwanted noise. This
      hospital-based, descriptive study was conducted at a Training Hospital in the
      Eastern part of Turkey, Trabzon, between 15-30 January 2016. It was participated
      by 248 volunteer nurses. Nurses express the noise of visitors (96.3%) on the
      first rank among the kinds of noise. The results of the study showed that most of
      the nurses were determined to use "a picture hanging technique on the wall"
      (53.2%) for preventing noise. No significant correlation was found between the
      descriptive characteristics of the nurses and nursing interventions to prevent
      noise (p> 0.05). A significant difference was found between the nurses working in
      internal medicine and surgical service in terms of the effect of noise on their
      work (p <0.05).

PMID- 29371731
TI  - Prevalence of Toxoplasma gondii oocysts through Copro-PCR in cats at Pet Center
      (UVAS), Lahore, Pakistan.
AB  - Toxoplasmosis is a major zoonotic disease of warm-blooded animals caused by
      Toxoplasma gondii. Cats are the only definitive host and they excrete
      environmentally resistant T. gondii oocysts in their faeces. Coproscopy was used
      to detect oocysts of enteric coccidians and then Copro-PCR was employed to test
      specifically for T. gondii in 470 cat samples. The prevalence of T. gondii
      oocysts was 2.3% (11/470) based on PCR. We observed 15 (3.2%) of 470 samples
      positive for coccidian oocysts by microscopy. The presence of Copro-DNA of T.
      gondii was found significantly higher (p<0.05) in males than females. We tested
      11 samples of T. gondii oocysts in which 9 samples were from coccidian oocysts
      positive samples and 2 samples from negative faecal samples. Our results showed
      that PCR is the reliable method for the detection of faecal oocysts of T. gondii
      in cats as compared to microscopy. As per our knowledge, ours is first study for
      Copro-PCR prevalence of cats' T. gondii oocysts excretion in Pakistan.

PMID- 29371732
TI  - Leukocyte adhesion defect: An uncommon immunodeficiency.
AB  - Leukocyte adhesion deficiency (LAD) is a rare primary immunodeficiency disorder
      with autosomal recessive inheritance which is characterized by presence of a
      defect of phagocytic function resulting from a lack of leukocyte cell surface
      expression of b2 integrin molecules (CD11 and CD18) that are essential for
      chemotaxis. The classic symptoms of the disease are failure of separation of the
      umbilical cord and recurrent bacterial infections, which continue throughout
      life. We describe here two cases of infants who presented with characteristic
      history of recurrent infections, delayed separation of umbilical cord and marked
      leukocytosis.

PMID- 29371733
TI  - Artery of Percheron Infarct - a diagnostic and prognostic conundrum!
AB  - A 39 year old male was found unconscious at home. On arrival to the hospital the
      patient was profoundly somnolent but easily rousable, with no focal neurological
      deficits. Imaging confirmed bilateral thalamic infarcts from the occlusion of
      Artery of Percheron, a rare anatomic variant which is a single arterial trunk
      supplying the thalamus and midbrain bilaterally. Anti-platelet therapy was
      initiated as soon as the diagnosis was established and the patient showed a rapid
      remarkable recovery over the next 48 hours. He continued to improve subsequently
      and was at baseline functional status at 6 months. Extensive investigations for
      etiologies were mostly unrevealing. In such patients presenting with
      drowsiness/somnolence, a posterior circulation stroke should be considered if no
      evidence of other more common causes are found. A CT head must be followed by an
      MRI to confirm the diagnosis and subsequent focus should be on eliciting risk
      factors and careful evaluation for etiologies.

PMID- 29371734
TI  - Haemophagocytic lymphohistiocytosis in a preterm infant: A case report.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a rare disease with a sepsis-like
      progression that leads to multiple organ dysfunction syndrome, especially in
      preterm infants. We present herein a case of HLH in a premature infant presenting
      with disseminated intravascular coagulopathy (DIC) and liver failure. A male
      infant, with weight 810g and delivered at the gestational age of 25 weeks and 2
      days, was misdiagnosed with tyrosinaemia for several weeks. He presented with
      anaemia, thrombocytopaenia, persistent DIC, and elevated liver enzymes despite
      continuous transfusion and broad-spectrum antibiotics. A bone marrow puncture
      biopsy revealed haemophagocytosis, leading to HLH diagnosis. It is important for
      paediatricians to consider the possibility of HLH when liver function test
      results are abnormal in such patients.

PMID- 29371735
TI  - Femoral artery pseudoaneurysm due to a gunshot injury.
AB  - Femoral artery pseudoaneurysms are commonly iatrogenic due to increasing use of
      the artery for arterial interventions. Other reasons of pseudoaneurysm formation
      are intravenous drug use and penetrating trauma. Here, we have discussed the
      management strategy of a femoral artery pseuodoaneursym and the modalities for
      preventing the misdiagnoses of the pseudoaneurysm in the emergency department. A
      50-year-old male patient was referred to our emergency department (ED) with
      claudication and severe local swelling. Ten days earlier, he had been referred to
      another ED immediately after a gunshot injury to the left inguinal zone. Duplex
      ultrasound and CT angiography of the left lower extremity revealed a 4 cm sac of
      pseudoaneurysm on the distal part of posterofemoral branch of deep femoral artery
      and a 9*10 cm haematoma on the posteromedial part of pseudoaneurysm. The patient
      underwent open repair surgery due to co-existing large haematoma and risk of
      infection. The patient was discharged after three days hospitalization. Pain,
      extremity oedema, pulsatile mass, femoral bruit, palpable thrill, and compressive
      neuropathy should alert the physician to possible femoral artery pseudoaneurysm.
      Duplex ultrasound and CT angiography are important diagnostic steps to reveal a
      possible life-threatening vascular injury.

PMID- 29371736
TI  - Small cell neuroendocrine carcinoma of nose and paranasal sinuses: The Shaukat
      Khanum Memorial Cancer Hospital experience and review of literature.
AB  - Small cell neuroendocrine carcinoma (SCNEC) is a rare disease of nose and
      paranasal sinuses. In contrast to other regions SCNEC of this region has been
      reported to be recurrent and locally aggressive. No definite treatment has been
      established till date because of rarity of this disease. The purpose of this
      descriptive study is to present the series of 8 cases with SNEC of nose and
      paranasal sinuses. Retrospective review of 8 patients presenting with Small cell
      neuroendocrine carcinoma of nose and paranasal sinuses, from January, 2005 to
      December, 2014 treated at Shaukat Khanum Memorial Cancer Hospital & Research
      Centre, Lahore was performed to determine the clinical characteristics and
      outcome of this disease. The subjects were 7 males and 1 female with a mean age
      of 45+/-15 years (range 24 to 59 years). Tumours were present in nasal cavity
      (n=4), ethmoid sinus (n=3) and maxillary sinus (n=1). Almost 50% of patients
      presented with AJCC stage IV-A. All patients had immunohistochemistry proven
      diagnosis. All patients (08) received radiotherapy with mean doses 58+/-Gy (Range
      54-66Gy). Surgery was performed in 2 while chemotherapy was administered in 4
      patients. Recurrence occurred in 3 patients, one each with loco-regional, distant
      and both. At a median follow up of 38 months, 5 patients were alive with no
      evidence of disease. SCNEC is a rare but aggressive neoplasm. Current standard of
      care varies but multi-modality approach should be the cornerstone in management
      of SCNEC. Early diagnosis and intervention improve the final outcome.

PMID- 29371737
TI  - Communication in diabetes care.

PMID- 29371738
TI  - The sixth vital sign in diabetes.
AB  - The vital signs are an integral part of clinical methods. In diabetes,
      determination of plasma glucose can be taken as the fifth vital sign. The sixth
      vital sign is well being, which can easily be measured by two item questionnaires
      designed to assess distress, depression and coping skills. This sign is essential
      for the screening and follow up of persons living with diabetes, as it provides
      an idea of quality of care, helps plan therapeutic interventions, and serves as a
      surrogate for prognosis or outcome. Inclusion of the sixth vital sign reflects
      the relevance of the bio-psychosocial model of health to diabetes care. .

PMID- 29371739
TI  - Role of extent of resection on quality of life in patients with newly diagnosed
      GBM.
AB  - Glioblastomas known for their adverse outcomes are most reportedly managed by
      surgical resection. Studies on the impact of (Extent of Resection) EOR against
      Quality of Life (QOL) are very limited. We have collected data from recent
      studies in this review to extract a general consensus among the neurosurgeons
      regarding the EOR. Key parameters like functional independence, neurocognitive
      improvements and global health status have been explored in the context of QOL.
      The currently available data suggests that an increased EOR may help improve QOL
      in GBM patients. With the help of recent advancements it may be possible to
      attain a better extent of resection while operating on GBMs.

PMID- 29371740
TI  - Epidemiology and parasitological survey of malarial parasites in Khyber
      Pakhtunkhwa, Pakistan.

PMID- 29371741
TI  - Awareness, use and perceptions about E-cigarettes among adult smokers in Karachi,
      Pakistan.
AB  - OBJECTIVE: To estimate the prevalence of awareness, current use and intention to
      use of e-cigarettes among adult smokers. METHODS: This cross-sectional survey was
      carried out at the Aga Khan University Hospital, Karachi, from July to August
      2016, and comprised people aged above 18 years who had smoked more than 100
      cigarettes in their lifetime. Convenience sampling method was used. A self
      administered questionnaire was used to collect data. SPSS 22 was used for data
      analysis.. RESULTS: Of the 387 participants, 359(92.8%) were male. The overall
      mean age was 32.4+/-12.6 years. Moreover, 215(55.5%) respondents belonged to the
      middle socio-economic class. Besides, 249(64.3%) respondents were aware of e
      cigarettes while 39(10.1%) used them, and 81(20.9%) wanted to use them. Socio
      economic status was the best predictor for awareness about e-cigarettes
      (p<0.001), while gender (p=0.001), occupation<lt;0.001) and current smoking
      status (p=0.009) were significantly associated with the use of e-cigarettes. E
      cigarettes were perceived as less harmful than tobacco cigarettes by 175(45.3%)
      respondents, helpful in quitting smoking by 138(35.6%), associated with chronic
      diseases by 158(40.9%), addictive 142(36.7%), and not safe during pregnancy by
      197(50.8%) participants. CONCLUSIONS: The percentage of e-cigarette usage was low
      despite the higher than expected awareness among the subjects.

PMID- 29371742
TI  - Multiple complications in sickle cell anaemia.
AB  - Sickle Cell Disease (SCD) is a structural haemoglobinopathy which is extremely
      diverse in its presentation regarding disease severity and organ involved. The
      homozygous form if poorly managed gives rise to numerous life threatening
      conditions which are otherwise avoidable. Here we report the case of a male
      adolescent with homozygous SCD who presented with haemolytic anaemia, massive
      ascites, hepatomegaly and multiple fractures secondary to severe malnourishment
      associated with the disease.

PMID- 29371743
TI  - A non-commutative Julia Inequality.
AB  - We prove a Julia inequality for bounded non-commutative functions on polynomial
      polyhedra. We use this to deduce a Julia inequality for holomorphic functions on
      classical domains in C d . We look at differentiability at a boundary point for
      functions that have a certain regularity there.

PMID- 29371744
TI  - Multiply robust imputation procedures for zero-inflated distributions in surveys.
AB  - Item nonresponse in surveys is usually treated by some form of single imputation.
      In practice, the survey variable subject to missing values may exhibit a large
      number of zero-valued observations. In this paper, we propose multiply robust
      imputation procedures for treating this type of variable. Our procedures may be
      based on multiple imputation models and/or multiple nonresponse models. An
      imputation procedure is said to be multiply robust if the resulting estimator is
      consistent when all models but one are misspecified. The variance of the imputed
      estimators is estimated through a generalized jackknife variance estimation
      procedure. Results from a simulation study suggest that the proposed procedures
      perform well in terms of bias, efficiency and coverage rate.

PMID- 29371745
TI  - Tropical Cyclone Diurnal Cycle as Observed by TRMM.
AB  - Previous work has indicated a clear, consistent diurnal cycle in rainfall and
      cold cloudiness coverage around tropical cyclones. This cycle may have important
      implications for structure and intensity changes of these storms and the
      forecasting of such changes. The goal of this paper is to use passive and active
      microwave measurements from the Tropical Rainfall Measuring Mission (TRMM)
      Microwave Imager (TMI) and Precipitation Radar (PR), respectively, to better
      understand the tropical cyclone diurnal cycle throughout a deep layer of a
      tropical cyclone's clouds. The composite coverage by PR reflectivity >=20 dBZ at
      various heights as a function of local standard time (LST) and radius suggests
      the presence of a diurnal signal for radii <500 km through a deep layer (2-10 km
      height) of the troposphere using 1998-2011 Atlantic tropical cyclones of at least
      tropical storm strength. The area covered by reflectivity >=20 dBZ at radii 100
      500 km peaks in the morning (0130-1030 LST) and reaches a minimum 1030-1930 LST.
      Radii between 300-500 km tend to reach a minimum in coverage closer to 1200 LST
      before reaching another peak at 2100 LST. The inner core (0-100 km) appears to be
      associated with a single-peaked diurnal cycle only at upper levels (8-10 km) with
      a maximum at 2230-0430 LST. The TMI rainfall composites suggest a clear diurnal
      cycle at all radii between 200 and 1000 km with peak rainfall coverage and rain
      rate occurring in the morning (0130-0730 LST).

PMID- 29371746
TI  - Clustered multistate models with observation level random effects, mover-stayer
      effects and dynamic covariates: modelling transition intensities and sojourn
      times in a study of psoriatic arthritis.
AB  - In psoriatic arthritis, it is important to understand the joint activity
      (represented by swelling and pain) and damage processes because both are related
      to severe physical disability. The paper aims to provide a comprehensive
      investigation into both processes occurring over time, in particular their
      relationship, by specifying a joint multistate model at the individual hand joint
      level, which also accounts for many of their important features. As there are
      multiple hand joints, such an analysis will be based on the use of clustered
      multistate models. Here we consider an observation level random-effects structure
      with dynamic covariates and allow for the possibility that a subpopulation of
      patients is at minimal risk of damage. Such an analysis is found to provide
      further understanding of the activity-damage relationship beyond that provided by
      previous analyses. Consideration is also given to the modelling of mean sojourn
      times and jump probabilities. In particular, a novel model parameterization which
      allows easily interpretable covariate effects to act on these quantities is
      proposed.

PMID- 29371747
TI  - A convergent, scalable and stereoselective synthesis of azole CYP51 inhibitors.
AB  - The study and development of azole-based CYP51 inhibitors is an active area of
      research across disciplines of biochemistry, pharmacology and infectious disease.
      Support of in vitro and in vivo studies require the development of robust
      asymmetric routes to single enantiomer products of this class of compounds.
      Herein, we describe a scalable and enantioselective synthesis to VNI and VFV, the
      two potent inhibitors of protozoan sterol 14alpha-demethylase (CYP51) that are
      currently under consideration for clinical trials for Chagas disease. A key
      transformation is the Jacobsen Hydrolytic Kinetic Resolution (HKR) reaction. The
      utility of the synthetic route is illustrated by the preparation of >25 g
      quantities of single enantiomers of VNI and VFV.

PMID- 29371748
TI  - Ixodid tick diversity on wild mammals, birds, and reptiles in and around Etosha
      National Park, Namibia.

PMID- 29371749
TI  - Does Intimate Partner Violence Decline as Women's Empowerment becomes Normative?
      Perspectives of Bangladeshi Women.
AB  - Studies addressing the relationship between women's empowerment and intimate
      partner violence (IPV) have yielded conflicting findings. Some suggest that
      women's economic and social empowerment is associated with an increased risk of
      intimate partner violence (IPV), arguably because men use often IPV to enforce
      their dominance and reassert inegalitarian gender norms when patriarchal norms
      are challenged; other studies suggest the converse. It is important to understand
      why these findings are contradictory to create a more sound basis for designing
      both women's empowerment interventions and anti-violence interventions. The aim
      of this study is to clarify the relationship between women's empowerment and IPV
      in a setting where gender roles are rapidly changing and IPV rates are high. We
      examine some of the ways in which the nature of women's empowerment evolved in
      six villages in rural Bangladesh during a 12-year period in which surveys have
      documented a decline of 11 points in the percentage of married women experiencing
      IPV in the prior year. The paper is based on data from 74 life history narratives
      elicited from 2011 to 2013 with recently married Bangladeshi women from the six
      villages, whom other community residents identified as empowered. Our findings
      suggest that women's empowerment has evolved in several ways that may be
      contributing to reductions in IPV: in its magnitude (for example, many women are
      earning more income than they previously did), in women's perceived exit options
      from abusive marriages, in the propensity of community members to intervene when
      IPV occurs, and in the normative status of empowerment (it is less likely to be
      seen as transgressive of gender norms). The finding that community-level
      perceptions of empowered women can evolve over time may go a long way in
      explaining the discrepant results in the literature.

PMID- 29371750
TI  - A model for straight and helical solar jets: II. Parametric study of the plasma
      beta.
AB  - Context: Jets are dynamic, impulsive, well-collimated plasma events that develop
      at many different scales and in different layers of the solar atmosphere. Aims:
      Jets are believed to be induced by magnetic reconnection, a process central to
      many astrophysical phenomena. Within the solar atmosphere, jet-like events
      develop in many different environments, e.g., in the vicinity of active regions
      as well as in coronal holes, and at various scales, from small photospheric
      spicules to large coronal jets. In all these events, signatures of helical
      structure and/or twisting/rotating motions are regularly observed. The present
      study aims to establish that a single model can generally reproduce the observed
      properties of these jet-like events. Methods: In this study, using our state-of
      the-art numerical solver ARMS, we present a parametric study of a numerical
      tridimensional magnetohydrodynamic (MHD) model of solar jet-like events. Within
      the MHD paradigm, we study the impact of varying the atmospheric plasma beta on
      the generation and properties of solar-like jets. Results: The parametric study
      validates our model of jets for plasma beta ranging from 10-3 to 1, typical of
      the different layers and magnetic environments of the solar atmosphere. Our model
      of jets can robustly explain the generation of helical solar jet-like events at
      various beta <= 1. This study introduces the new original result that the plasma
      beta modifies the morphology of the helical jet, explaining the different
      observed shapes of jets at different scales and in different layers of the solar
      atmosphere. Conclusions: Our results allow us to understand the energisation,
      triggering, and driving processes of jet-like events. Our model allows us to make
      predictions of the impulsiveness and energetics of jets as determined by the
      surrounding environment, as well as the morphological properties of the resulting
      jets.

PMID- 29371751
TI  - Physiological relevance of covalent protein modification by dietary
      isothiocyanates.
AB  - Isothiocyanates (ITCs), naturally occurring in abundance in cruciferous
      vegetables, are the most well-studied organosulfur compounds having an
      electrophilic reactivity. ITCs have been accepted as major ingredients of these
      vegetables that afford their health promoting potentials. ITCs are able to
      modulate protein functions related to drug-metabolizing enzymes, transporters,
      kinases and phosphatases, etc. One of the most important questions about the
      molecular basis for the health promoting effects of ITCs is how they modulate
      cellular target proteins. Although the molecular targets of ITCs remains to be
      validated, dietary modulation of the target proteins via covalent modification by
      ITCs should be one of the promising strategies for the protection of cells
      against oxidative and inflammatory damage. This review discusses the plausible
      target proteins of dietary ITCs with an emphasis on possible involvement of
      protein modification in their health promoting effects. The fundamental knowledge
      of ITCs is also included with consideration of the chemistry, intracellular
      behavior, and metabolism.

PMID- 29371753
TI  - Clinical significance of redox effects of Kampo formulae, a traditional Japanese
      herbal medicine: comprehensive estimation of multiple antioxidative activities.
AB  - To clarify the clinical significance of the redox-controlling effects of Kampo, a
      traditional Japanese herbal medicine, we determined the scavenging activities of
      various reactive oxygen species in clinically used Kampo formulae using an
      electron spin resonance-based technique. Formulae containing Rhei Rhizoma (i.e.,
      mashiningan and daiobotanpito) showed high scavenging activity against the
      alkoxyl radical, and crude extract quantity was significantly correlated with
      scavenging activity. Hydroxyl radical scavenging activity was positively
      correlated with the quantity of Zingiberis Rhizoma. Strong hydroxyl radical
      scavenging activity was also found in formulae containing both Bupleuri Radix and
      Scutellariae Radix, a widely used anti-inflammatory combination. Formulae
      containing a clinically common combination of Scutellariae Radix, Coptidis
      Rhizoma, and Phellodendri Cortex induced high superoxide scavenging activity.
      Singlet oxygen scavenging activity was high in formulae containing Bupleuri Radix
      and Glycyrrhizae Radix. In contrast, formulae containing Rehmanniae Radix showed
      generally low reactive oxygen species scavenging activities, and the quantity of
      Rehmanniae Radix was negatively correlated with hydroxyl radical and singlet
      oxygen scavenging activities. These results indicate that the antioxidative
      effects of Kampo formulae are not uniform but complexly varied against multiple
      reactive oxygen species. Some formulae have almost no antioxidant effects but may
      act as pro-oxidants.

PMID- 29371752
TI  - How is edaravone effective against acute ischemic stroke and amyotrophic lateral
      sclerosis?
AB  - Edaravone is a low-molecular-weight antioxidant drug targeting peroxyl radicals
      among many types of reactive oxygen species. Because of its amphiphilicity, it
      scavenges both lipid- and water-soluble peroxyl radicals by donating an electron
      to the radical. Thus, it inhibits the oxidation of lipids by scavenging chain
      initiating water-soluble peroxyl radicals and chain-carrying lipid peroxyl
      radicals. In 2001, it was approved in Japan as a drug to treat acute-phase
      cerebral infarction, and then in 2015 it was approved for amyotrophic lateral
      sclerosis (ALS). In 2017, the U.S. Food and Drug Administration also approved
      edaravone for treatment of patients with ALS. Its mechanism of action was
      inferred to be scavenging of peroxynitrite. In this review, we focus on the
      radical-scavenging characteristics of edaravone in comparison with some other
      antioxidants that have been studied in clinical trials, and we summarize its
      pharmacological action and clinical efficacy in patients with acute cerebral
      infarction and ALS.

PMID- 29371755
TI  - The expression of Toll-like receptor 5 in preterm histologic chorioamnionitis.
AB  - Spontaneous preterm birth is often caused by chorioamnionitis. Toll-like
      receptors (TLRs) have a role in the response of the innate immune system. The
      role of TLR5 in chorioamnionitis remains unclear: however, TLR5 was reported to
      have a significantly stronger effect on the induction of interleukin (IL)-6 when
      compared with other TLRs in amniotic epithelial cells. The aim of this study was
      to investigate TLR5 expression in placentas with preterm histologic
      chorioamnionitis (HCA). The expression levels of TLR5 were evaluated in the
      amnions, chorions, deciduae and villi with and without HCA using
      immunohistochemistry. The co-localization of IL-6 or IL-8 with TLR5 was examined
      by immunofluorescence. The production of IL-6 was examined in primary tissue
      cultured fetal membranes treated with and without the TLR5 agonist. The protein
      expression of TLR5 was significantly increased in amnions with HCA (p<0.05) and
      showed a trend toward an increase in chorions with HCA, whereas no significant
      difference was detected in the villi and decidua. TLR5 co-localized with IL-6 and
      IL-8 in amnions and chorions. IL-6 showed a significant increase (p<0.05) with
      the TLR5 agonist. These results suggest that TLR5 plays a role in the
      pathogenesis of preterm HCA and IL-6 production.

PMID- 29371754
TI  - Glutathione homeostasis is significantly altered by quercetin via the Keap1/Nrf2
      and MAPK signaling pathways in rats.
AB  - Previously, we showed that 0.5% quercetin simultaneously decreased serum
      homocysteine and glutathione (GSH) levels in rats. The aim of the present study
      was to investigate the effects of 0.5% quercetin on GSH metabolism, related
      enzymes and signal pathways in rats. Rats were fed the control diet and 0.5%
      quercetin-supplemented diet for 6 weeks. The results showed that quercetin
      reduced serum and hepatic content of GSH and the ratio of GSH and oxidized
      glutathione (GSSG), enhanced hepatic activity and mRNA expression of glutathione
      S-transferase (GST), inhibited hepatic activity and mRNA expression of glutamate
      cysteine ligase (GCL), and decreased hepatic glutathione reductase (GR) mRNA
      expression. Levels of phosphorylated p38 and extracellular signal-regulated
      kinase (ERK) 1/2 mitogen-activated protein kinases (MAPKs) increased, while that
      of nuclear factor E2-like 2 (Nrf2) protein decreased after quercetin treatment.
      However, no significant hepatotoxicity was noted. We concluded that quercetin
      treatment altered hepatic GSH metabolism by modulating GSH metabolic enzyme
      activities and mRNA expression in rats, and p38, ERK1/2 MAPKs, and Nrf2 were
      involved in modulating GSH metabolism-related enzymes.

PMID- 29371756
TI  - The age-related changes of dietary phosphate responsiveness in plasma 1,25
      dihydroxyvitamin D levels and renal Cyp27b1 and Cyp24a1 gene expression is
      associated with renal alpha-Klotho gene expression in mice.
AB  - In this study, we investigated the relationship between age-related changes in
      renal alpha-Klotho gene expression, vitamin D metabolism and the responsiveness
      of dietary phosphate in 1, 2 and 13 month-old mice fed a high phosphate
      (phosphate 1.2%) diet or low phosphate (phosphate 0.02%) diet for 5 days. We
      found that 1,25-dihydroxyvitamin D levels in plasma were significantly lower in
      the high phosphate group than the low phosphate group for 1 and 2 month-old mice,
      but not 13 month-old mice. In addition, in the high phosphate group plasma 1,25
      dihydroxyvitamin D levels were decreased in 2 month-old mice relative to 1 month
      old mice, but 13 month-old mice had higher levels than 2 month-old mice. In fact,
      plasma 1,25-dihydroxyvitamin D levels showed a significant correlation with
      vitamin D metabolism gene Cyp27b1 and Cyp24a1 mRNA expression in the high
      phosphate group. Interestingly, renal alpha-Klotho mRNA and protein levels were
      significant change with age. Furthermore, alpha-Klotho mRNA expression showed a
      significant negative correlation with plasma 1,25-dihydroxyvitamin D levels in
      the high phosphate group. Our results suggest that age-related alterations in
      renal alpha-Klotho expression could affect the responsiveness of dietary
      phosphate to vitamin D metabolism.

PMID- 29371757
TI  - Daily intake of broccoli sprouts normalizes bowel habits in human healthy
      subjects.
AB  - Chronic oxidative stress impairs regular defecation. Sulforaphane (SFN) enhances
      anti-oxidant systems, ameliorating oxidative injury. SFN inhibits overgrowth of
      anaerobic microflora and protects small intestine from oxidative injury. We
      assessed whether daily intake of SFN-rich broccoli sprouts (BS) improves
      defecation in humans. Forty-eight subjects, with a constipation scoring system
      (CSS) >2 points, were assigned to either the BS group (n = 24) or the alfalfa
      sprouts (AS) group (n = 24), and were requested to eat 20 g daily of raw BS or
      AS, respectively, for 4 weeks. BS contains 4.4 mg/g sulforaphane glucosinolates
      (SGS), while AS contains no SGS. CSS-based questionnaires were performed to
      evaluate bowel habit. Stool samples were collected to evaluate intestinal
      microflora using a terminal restriction fragment length polymorphism flora
      analysis. Intervention with BS, but not AS, caused a significant decrease in the
      duration of attempted defecation and the total CSS score. Intervention with BS
      decreased the percentage of Bifidobacterium in the stool. These results suggest
      that daily intake of BS improves bowel habit in human subjects. Since BS
      treatment enhance antioxidant enzyme activities, these effects of BS appear to
      relate with the SFN-mediated modulation of the intestinal motility during
      exposure to oxidative stress. (UMIN Clinical Trial Registration Number: UMIN
      000021207).

PMID- 29371758
TI  - Dietary inflammatory index and its relationship with high-sensitivity C-reactive
      protein in Korean: data from the health examinee cohort.
AB  - Inflammation is associated with chronic disease. High-sensitivity C-reactive
      protein (hs-CRP) is a predictor of chronic disease. The dietary inflammatory
      index (DII) is used to determine the overall inflammatory potential of diet. A
      cross-sectional analysis of Health Examinee cohort data (2012-2014) from Korea
      was performed. Subjects were 40-79 years of age (8,332 males; 19,754 females).
      The DII was used to analyze the relationship between subject characteristics,
      nutrient intake, and the hs-CRP. Additionally, the relationship between DII and
      hs-CRP as a predictor of chronic disease was examined. The DII was divided into 4
      quartile: Q1 = -7.21 to -1.88 (median: -3.020), Q2 = -1.87 to -0.02 (median: 
      0.410), Q3 = -0.01 to 1.87 (median = 0.870) and Q4 = 1.88 to 7.34 (median =
      3.040). For each group, the carbohydrate/protein/fat intake ratio was Q1 =
      66.7:16.6:19.2, Q2 = 67.2:15.6:18.7, Q3 = 67.3:15.1:18.4 and Q4 = 67.3:14.0:17.9.
      The odds of elevated hs-CRP were 1.241 times higher in participants with the most
      proinflammatory diets than those with the most anti-inflammatory diets [hs-CRP;
      odds ratio (95% confidence interval) for Q4 vs Q1: 1.241 (1.071, 1.438); p for
      trend = 0.002]. An association was found between a high DII and high levels of hs
      CRP. The DII may be applied to measure the association between diet and chronic
      diseases.

PMID- 29371759
TI  - Dietary calcium intake is associated with serum high-sensitivity C-reactive
      protein level in the general Japanese population.
AB  - The beneficial effects of dietary calcium intake on high-sensitivity C-reactive
      protein levels, a risk factor of cardiovascular disease, have not been fully
      elucidated. This study investigated the associations between dietary calcium
      intake and serum high-sensitivity C-reactive protein levels in the general
      Japanese population. We analyzed the data of 2,019 subjects (1,194 men and 825
      women) aged 35 to 69 years in a cross-sectional study of the Japan Multi
      Institutional Collaborative Cohort Study. Nutrients intake including calcium were
      estimated using a validated food-frequency questionnaire. Analysis using a
      general linear model revealed that dietary calcium intake was inversely
      associated with serum high-sensitivity C-reactive protein levels (p for trend
      <0.001) after adjustment for age, sex, research group, leisure-time physical
      activity, smoking habit, drinking habit, dietary intakes (energy, dietary fiber,
      saturated fatty acids and vitamin D) and menopausal status. The association was
      slightly attenuated after additional adjustment for body mass index; however,
      remained significant (p for trend = 0.008). There were no significant
      interactions between dietary calcium intakes and sex, body mass index, or vitamin
      D intake for high-sensitivity C-reactive protein levels. This study have
      demonstrated that dietary calcium intake was inversely associated with serum high
      sensitivity C-reactive protein levels in the general population.

PMID- 29371760
TI  - The relationship between vitamin D and estimated glomerular filtration rate and
      urine microalbumin/creatinine ratio in Korean adults.
AB  - The present study was conducted to assess the association between 25
      hydroxyvitamin D [25(OH)D], estimated glomerular filtration rate (eGFR) and urine
      microalbumin/creatinine ratio (uACR) in Korean adults. Data on 4,948 adults aged
      >=20 years from the Korean National Health and Nutrition Examination Survey V-3
      (2012) were analyzed. After adjusting for the related variables (except age), the
      odds ratios (ORs) of vitamin D deficiency with the normal group as a reference
      were significantly higher in the decreased eGFR plus elevated uACR group [3.089
      (95% CI, 1.722-5.544)], but not in the elevated uACR [1.247 (95% CI, 0.986
      1.577)] and decreased eGFR group [1.303 (95% CI, 0.789-2.152)]. However, when
      further adjusting for age, the ORs of vitamin D deficiency with the normal group
      as a reference were significantly higher in the elevated uACR group [1.312 (95%
      CI, 1.035-1.662)], decreased eGFR group [1.761 (95% CI, 1.062-2.919)] and the
      decreased eGFR plus elevated uACR group [3.549 (95% CI, 1.975-6.365)]. In
      conclusion, vitamin D deficiency was positively associated with the elevated uACR
      and decreased eGFR. In addition, vitamin D level decreased greatly when decreased
      eGFR and elevated uACR appeared simultaneously.

PMID- 29371761
TI  - The influence of long-term use of proton pump inhibitors on the gut microbiota:
      an age-sex-matched case-control study.
AB  - Proton pump inhibitors (PPIs) are widely used to treat gastro-esophageal reflux
      and prevent gastric ulcers, and have been considered as low risk. However, recent
      studies have identified possible associations between PPI use and gut microbiota,
      suggesting that PPIs use increases the risk of enteric infections, including
      Clostridium difficile infection. To investigate gut microbiota in Japanese PPIs
      users, we conducted 16S metagenomics analysis of fecal samples collected from PPI
      users and healthy adults. In total, 36 PPI users and 36 PPI non-users (as control
      subjects) matched by age and sex were recruited and fecal samples were obtained
      to analyze the gut microbiome using 16S rRNA gene sequencing. There were
      significant differences in the microbial structure between PPI non-users and PPI
      users. In contrast, the analysis of alpha-diversity revealed no significant
      differences between PPI non-users and PPI users. When comparing in genus level
      between these two groups, the genera Streptococcus was significantly abundant and
      the genera Faecalibacterium was significantly decreased in PPI users. Our
      findings indicate a probable association between PPI use and the alternation of
      microbiota. These alterations might provide a mechanism by which PPIs predispose
      enteric infection such as Clostridium difficile infection.

PMID- 29371762
TI  - Effects of Maternal Work Incentives on Youth Crime.
AB  - This study exploits differences in the implementation of welfare reform across
      states and over time to identify causal effects of maternal work incentives, and
      by inference employment, on youth arrests between 1988 and 2005, the period of
      time during which welfare reform unfolded. We consider both serious and minor
      crimes as classified by the Federal Bureau of Investigation, consider
      differential effects by the youth's gender and age, investigate the extent to
      which effects were stronger in states with more stringent work incentive policies
      and larger welfare caseload declines, and use a number of different model
      specifications to assess robustness and patterns. We find that welfare reform led
      to reduced arrests for minor crime among youth ages 15-17 years by 9-11 %, with
      similar estimates for males and females, but that it did not affect youth arrests
      for serious crimes. The results from this study add to a scant knowledge base
      about the effects of maternal employment on adolescent behavior by exploiting a
      large-scale social experiment that greatly increased employment of low-skilled
      women. The results also provide some support for the widely-embraced argument
      that welfare reform would discourage undesirable social behavior, not only of
      mothers, but also of the next generation.

PMID- 29371763
TI  - Gene Editing in Clinical Practice.

PMID- 29371764
TI  - Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase
      Gene With Nosyndromic Cleft Lip/Palate (nsCL/P).
AB  - Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and
      the epigentic process of DNA methylation. It has been reported that abnormal DNA
      methylation contributes to the pathogenesis of congenital anomalies. There were
      many published case control studies assessing the associations of MTHFR C677T
      polymorphism with risks of nosyndromic cleft lip with and without palate
      (nsCL/P), but with inconsistent results. To derive a more precise estimation of
      the relationship, a meta-analysis was performed. Eligible articles were
      identified by search of databases including PubMed, Science Direct, Google
      Scholar and Springer Link up to December, 2015. Finally, a total of 22 studies
      with 3724 nsCL/P cases and 5275 controls were included in the present meta
      analysis. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs)
      were pooled to assess the association. Subgroup analysis based on ethnicity was
      also performed. All statistical analyses were done by MIX program. Meta-analysis
      results suggested that MTHFR C677T polymorphism contributed to the increased
      nsCL/P risk in overall population using four genetic models except homozygote
      model (for T vs. C: OR = 1.24, 95% CI = 1.1-1.4; for TT + CT vs. CC: OR = 1.29,
      95% CI = 1.04-1.59; for CT vs. CC: OR = 1.26, 95% CI = 0.98-1.63; for TT vs. CC:
      OR = 1.02, 95% CI = 0.74-1.4; for TT vs. CT + CC: OR = 1.36, 95% CI = 1.05-1.74).
      In conclusion, results of present meta-analysis suggested that MTHFR C677T
      polymorphism is significantly associated with nonsyndromic orofacial cleft.

PMID- 29371765
TI  - Role of Homocysteine in Cognitive Impairement and Alzheimer's Disease.
AB  - A high circulating concentration of the non proteinogenic amino acid homocysteine
      has been implicated as a risk factor for Alzheimer's Disease and its prodromal
      stage, mild cognitive impairement. Furthermore, hyperhomocysteinaemia has been
      directly attributed to a deficiency in vitamins B12, folate, and B6. Several
      studies have demonstrated decrease in progression of mild cognitive impairement
      to Alzheimer's Disease, and some have even shown an improvement in cognition
      after vitamin supplements with B12 and folate. Plausible mechanisms linking
      hyperhomocysteinaemia to Alzheimer's and cognitive impairement have been
      hypothesized and demonstrated in hyperhomocysteinemic mice models. However, some
      studies have not elucidated any benefit of vitamin supplements in subjects with
      cognitive impairment. Hence, multicentric clinical studies need to be conducted
      to substantiate the mechanisms of neuronal degeneration due to
      hyperhomocysteinaemia and to demonstrate the beneficial effect of folate, B6 and
      B12 supplements on cognition.

PMID- 29371767
TI  - Study on Impact of Iron and Folic Acid on the Plasma Trace Minerals in Pregnant
      Anemic Women.
AB  - Iron deficiency anemia is one of the causes that lead to significant mortality
      and morbidity among pregnant women and fetus. The present study was undertaken to
      explore oral iron supplementation can modify the metal contents in pregnant
      anemic women. Iron and folic acid supplementations was given to 500 anemic women
      (mild = 200, moderate = 200, and severe = 100) and 100 age matched non-anemic
      controls daily for 100 days. Blood index values and plasma trace minerals were
      estimated as per standard protocols. Haemoglobin and ferritin levels were found
      significantly increased (p < 0.001) in anemic and control subjects after
      treatment. Moreover, the serum transferring receptor levels and total iron
      binding capacity were found significantly decreased in all treated groups. Iron
      (Fe), zinc (Zn) and copper (Cu) levels were found increased (p < 0.01) after oral
      iron supplementation groups. Moreover, selenium (Se) manganese (Mn) and were
      found to be decreased in all treated groups. Data provides the conclusion that
      iron and folic acid supplementation recovered the essential trace minerals,
      except manganese, which may lead to various complications including peroxidation
      of vital body molecules resulting in increased risk for pregnant women as well as
      fetus.

PMID- 29371766
TI  - Possible Role of microRNA-122 in Modulating Multidrug Resistance of
      Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a hypervascular primary liver cancer
      characterized by rapid progression, besides, resistance to traditional
      chemotherapeutic agents. It has been shown that microRNAs play critical roles in
      regulation of tumor cell sensitivity to drugs through modulating the expression
      of genes involved in drug transport. The present study investigated whether
      restoration of miR-122 in HCC cells could alter the cell cycle distribution and
      the expression of multidrug resistance (MDR)-related genes (ABCB1, ABCC1, ABCG2
      and ABCF2). After overexpression of miR-122 in HepG2 cells treated or untreated
      with doxorubicin doses, total RNAs and protein extracts were isolated for
      application of QRT-PCR and western blotting techniques. Moreover, cell cycle
      distribution was monitored by flow cytometry. Our results revealed that, the over
      expression of miR-122 in HepG2 cells treated or untreated with doxorubicin could
      modulate the sensitivity of cells to chemotherapeutic drug through downregulation
      of MDR-related genes, ABCB1 and ABCF2. Interpretation of cell cycle distribution
      revealed that, the anti-proliferative effect of miR-122 is associated with the
      accumulation of cells in G0/G1 phase. Moreover, treatment with miR-122 and
      doxorubicin resulted in high percentage of HCC cells in G0/G1 phase. Taken
      together, our findings revealed that, overexpression of miR-122 inhibited HCC
      cell growth by inducing cell cycle arrest and this arrest is associated with down
      regulation of MDR-related genes.

PMID- 29371768
TI  - Altered Kinetics Properties of Erythrocyte Lactate Dehydrogenase in Type II
      Diabetic Patients and Its Implications for Lactic Acidosis.
AB  - Recent studies have been noted that the erythrocytes from Type II diabetic
      patients show significantly altered structural and functional characteristics
      along with the changed intracellular concentrations of glycolytic intermediates.
      More recent studies from our laboratory have shown that the activities of enzymes
      of glycolytic pathway changed significantly in RBCs from Type II diabetic
      patients. In particular the levels of lactate dehydrogenase (LDH) increased
      significantly. Lactic acidosis is an established feature of diabetes and LDH
      plays a crucial role in conversion of pyruvate to lactate and reportedly, the
      levels of lactate are significantly high which is consistent with our observation
      on increased levels of LDH. Owing to this background, we examined the role of
      erythrocyte LDH in lactic acidosis by studying its kinetics properties in Type II
      diabetic patients. Km, Vmax and apparent catalytic efficiency were determined
      using pyruvate and NADH as the substrates. With pyruvate as the substrate the Km
      values were comparable but Vmax increased significantly in the diabetic group.
      With NADH as the substrate the enzyme activity of the diabetic group resolved in
      two components as against a single component in the controls. The Apparent Kcat
      and Kcat/Km values for pyruvate increased in the diabetic group. The Ki for
      pyruvate increased by two fold for the enzyme from diabetic group with a marginal
      decrease in Ki for NADH. The observed changes in catalytic attributes are
      conducive to enable the enzyme to carry the reaction in forward direction towards
      conversion of pyruvate to lactate leading to lactic acidosis.

PMID- 29371769
TI  - Characterization and Classification of Mesenchymal Stem Cells in Several Species
      Using Surface Markers for Cell Therapy Purposes.
AB  - Mesenchymal stem cells are multipotent cells capable of replicating as
      undifferentiated cells, and have the potential of differentiating into
      mesenchymal tissue lineages such as osteocytes, adipocytes and chondrocytes. Such
      lineages can then be used in cell therapy. The aim of present study was to
      characterize bone marrow derived mesenchymal stem cells in four different
      species, including: sheep, goat, human and mouse. Human bone-marrow mesenchymal
      stem cells were purchased, those of sheep and goat were isolated from fetal bone
      marrow, and those of mouse were collected by washing bone cavity of femur and
      tibia with DMEM/F12. Using flow-cytometry, they were characterized by CD surface
      antigens. Furthermore, cells of third passage were examined for their osteogenic
      and adipogenic differentiation potential by oil red and alizarin red staining
      respectively. According to the results, CD markers studied in the four groups of
      mesenchymal stem cells showed a different expression. Goat and sheep expressed
      CD44 and CD166, and weakly expressed CD34, CD45, CD105 and CD90. Similarly, human
      and mouse mesenchymal cells expressed CD44, CD166, CD105 and CD90 whereas the
      expression of CD34 and CD45 was negative. In conclusion, although all mesenchymal
      stem cells display plastic adherence and tri-lineage differentiation, not all
      express the same panel of surface antigens described for human mesenchymal stem
      cells. Additional panel of CD markers are necessary to characterize regenerative
      potential and possible application of these stem cells in regenerative medicine
      and implantology.

PMID- 29371770
TI  - Analysis of Association of Angiotensin II Type 1 Receptor Gene A1166C Gene
      Polymorphism with Essential Hypertension.
AB  - The A/C transversion at 1166 of the angiotensin II Type 1 Receptor (AT1R) gene
      per se does not characterize any functional diversity but has been associated
      with expression of the AT1R, consequently molecular variants of the gene may
      modulate the possible risk of essential hypertension. The present study was
      performed to determine the genotypic frequency of the A1166C polymorphism of the
      AT1R gene in essential hypertensive patients with the aim to assess the effect of
      variants of this polymorphism in hypertension. AT1R gene amplification was
      performed by PCR and A1166C polymorphism was determined by enzyme digestion
      methodologies in 224 consecutively enrolled essential hypertensive patients and
      257 controls. Suitable descriptive statistics was used for different variables.
      Results revealed that genotype and allele distribution of the A1166C variant
      differed significantly in hypertensives and normotensives. Allele frequency at
      the A1166C position was 61%A and 39%C for control and 52%A and 48%C for patients.
      Observed frequencies were compatible with HWE expected frequencies in cases as
      well as in controls. rs5186 was found to be associated with hypertension (95% CI
      1.1453-2.7932, p: 0.0106). The difference remained statistically significant
      after the multivariate adjustment (p < 0.05), with C/C variant conferring a risk
      of 1.74-fold of essential hypertension. This association was confirmed by inter
      genotypic variations in the mean systolic and diastolic blood pressure in
      patients. In conclusion, genetic variation at the AT1R gene influences the risk
      of hypertension stratification and might serve as a predictive marker for the
      susceptibility to hypertension among affected families.

PMID- 29371771
TI  - Effect of Interaction Between Duration of Alcohol Consumption and Alcohol
      Dependence on Thyroid Function Test: Cross Sectional Observational Study.
AB  - Dependence on alcohol, nicotine and duration of alcohol consumption are known to
      alter thyroid function tests. This study was conducted to assess the effect of
      interaction between the duration of alcohol consumption and alcohol dependence on
      TFT. The subjects consisted of 38 male patients with alcohol dependent syndrome
      co morbid with nicotine dependent syndrome, 33 male patients with alcohol
      dependent syndrome and 30 male normal healthy volunteers. Liver function tests,
      haematological parameters and thyroid function tests were assayed. Two way
      multivariate ANOVA was used to assess the interaction effect by SPSS 21 package.
      Multivariate analysis of combined TFT levels revealed no significant (P = .078)
      difference amongst groups based on alcohol dependence, significant difference (P
      = .001) amongst groups based on duration of alcohol consumption and no
      significant (P = .604) interaction effect between duration of alcohol consumption
      and alcohol dependence. Tests of between subject effects for individual TFT
      revealed significant (P = .014) difference in T3 between groups based on alcohol
      dependence, significant difference in the levels of fT4 (P = .001), T3 (P = .07)
      and T4 (P < .001) between groups based on duration of alcohol consumption was
      observed. Interaction between the effect of duration of alcohol consumption and
      alcohol dependence for individual TFT did not reveal any significance. fT4, TSH
      and T4 levels were significantly low in persons consuming alcohol for more than
      20 years. TSH levels were significantly low in ADS compared to controls.
      Significant decrease in the levels of thyroid hormones was observed as the
      duration of alcohol consumption increased.

PMID- 29371772
TI  - Dietary Fats and Oxidative Stress: A Cross-Sectional Study Among Coronary Artery
      Disease Subjects Consuming Coconut Oil/Sunflower Oil.
AB  - Coconut oil has been used by the people of Kerala as a cooking medium for several
      decades. Due to its alleged hypercholesterolemic activity, general population in
      recent times is shifting to cooking oils rich in polyunsaturated fats, the most
      popular being sunflower oil. The effect of long-term consumption of sunflower oil
      on oxidative stress in humans is not well investigated. We studied oxidative
      stress among coronary artery disease (CAD) patients who were consuming coconut
      oil or sunflower oil as a part of their routine diet. Men, aged 35-70 years, with
      established CAD, who presented to the hospital for routine cardiac evaluations,
      were enrolled in this observational study. Group 1 and 2 consisted of 73 and 80
      subjects consuming coconut oil and sunflower oil respectively for over a period
      of 2 years. Lipid profile and parameters for oxidative stress were evaluated
      among them. Conventional lipid parameters did not differ significantly between
      the two groups. Mean vitamin C concentration was significantly reduced for
      subjects on sunflower oil compared to those consuming coconut oil (P = 0.044).
      Malondialdehyde was higher for sunflower oil consumers compared to coconut oil
      consumers (P < 0.0001). Other parameters such as oxidized LDL, GSH, GPx and SOD
      were not found to be significantly different between the two groups. The results
      of the present study show that coconut oil did not induce hypercholesterolemia
      compared to sunflower oil. On the other hand, sunflower oil group had elevated
      oxidative stress compared to coconut oil group.

PMID- 29371773
TI  - The Effects of Onion Consumption on Prevention of Nonalcoholic Fatty Liver
      Disease.
AB  - It is well known that dietary intakes play a pivotal role in pathogenesis of
      nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH);
      however, the role of each component of diet has not yet been elucidated. Our
      objective was to evaluate the effects of onion consumption on prevention of
      NAFLD/NASH development. Sprague-Dawley rats were fed either high-fat, high sugar
      diet (model group), or high-fat, high sugar diet plus 7% onion powder (model +
      onion), or chow diet ad libitum for 7 weeks. Serum levels of fasting glucose,
      triglyceride, cholesterol, liver enzymes, insulin, and hepatic tumor necrosis
      factor-alpha (TNF-alpha) gene expression were determined. Hepatic histology was
      examined by H&E stain. Model + onion group had significantly lower hepatic
      steatosis, ballooning, lobular inflammation, and portal inflammation (p < 0.001),
      lower hepatic TNF-alpha gene expression (p < 0.001), lower plasma levels of ALT
      (p = 0.026), AST (p = 0.041), insulin (p < 0.001), TG (p = 0.041), and glucose (p
      = 0.009) compared with model group; however, weight gain, food intake, plasma
      total cholesterol and LDL levels were not significantly different between these
      two groups. Our data indicate that regular consumption of onion can prevent NAFLD
      even in the presence of the other risk factors such as obesity,
      hypercholesterolemia, and high energy, fat, and sugar intakes.

PMID- 29371774
TI  - A Study of Microalbuminuria (MAU) and Advanced Glycation End Products (AGEs)
      Levels in Diabetic and Hypertensive Subjects.
AB  - The prevalence of non-communicable diseases like diabetes mellitus (DM) and
      hypertension (HTN) is growing worldwide. Both lead to nephropathy if not
      controlled effectively. Microalbuminuria (MAU) is recognized as an early
      predictor for nephropathy. Additionally, the timely detection of advanced
      glycation end products (AGEs) is also considered to be an important prognostic
      factor for diabetic nephropathies. Hence, screening for the early detection of
      MAU and AGEs would be an useful and relatively inexpensive laboratory test for
      early clinical diagnosis for the incidence of nephropathy in these diseases. This
      study was conducted in DM, HTN and pregnancy induced hypertensive (PIH) subjects.
      MAU and Nepsilon-Carboxymethyllysine (CML) levels were estimated by in-house RIA
      kits in the patient groups and controls, while the total AGEs level in serum was
      determined by ELISA. The levels of MAU, CML and AGE-BSA were observed to be
      significantly higher in DM, HTN and PIH subjects compared to controls (p <
      0.001). Increased serum CML and AGEs levels in DM, HTN and PIH subjects indicated
      ongoing glycemic damage and their susceptibility to develop renal complications.

PMID- 29371775
TI  - Validating a High Performance Liquid Chromatography-Ion Chromatography (HPLC-IC)
      Method with Conductivity Detection After Chemical Suppression for Water Fluoride
      Estimation.
AB  - A variety of methods, including the Ion Selective Electrode (ISE), have been used
      for estimation of fluoride levels in drinking water. But as these methods suffer
      many drawbacks, the newer method of IC has replaced many of these methods. The
      study aimed at (1) validating IC for estimation of fluoride levels in drinking
      water and (2) to assess drinking water fluoride levels of villages in and around
      Vellore district using IC. Forty nine paired drinking water samples were measured
      using ISE and IC method (Metrohm). Water samples from 165 randomly selected
      villages in and around Vellore district were collected for fluoride estimation
      over 1 year. Standardization of IC method showed good within run precision,
      linearity and coefficient of variance with correlation coefficient R2 = 0.998.
      The limit of detection was 0.027 ppm and limit of quantification was 0.083 ppm.
      Among 165 villages, 46.1% of the villages recorded water fluoride levels >1.00
      ppm from which 19.4% had levels ranging from 1 to 1.5 ppm, 10.9% had recorded
      levels 1.5-2 ppm and about 12.7% had levels of 2.0-3.0 ppm. Three percent of
      villages had more than 3.0 ppm fluoride in the water tested. Most (44.42%) of
      these villages belonged to Jolarpet taluk with moderate to high (0.86-3.56 ppm)
      water fluoride levels. Ion Chromatography method has been validated and is
      therefore a reliable method in assessment of fluoride levels in the drinking
      water. While the residents of Jolarpet taluk (Vellore distict) are found to be at
      a high risk of developing dental and skeletal fluorosis.

PMID- 29371776
TI  - Mutations in HNF1A Gene are not a Common Cause of Familial Young-Onset Diabetes
      in Iran.
AB  - Mutations in hepatocyte nuclear factor-1 alpha (HNF1A) as a homeodomain
      transcription factor which regulates variety of genes, are the most common cause
      of maturity-onset diabetes of the young (MODY). Detection of HNF1A mutations not
      only classifies the subtype, but also predicts the likely clinical course and may
      alters the method of treatment from insulin to the oral sulphonylureas, which is
      shown to improve glycemic control. The coding and promoter regions of HNF1A gene
      were screened for mutations in 34 unrelated Iranian MODY patients. We identified
      one novel missense mutation (C49G) and two novel polymorphisms and 8 recently
      identified SNPs in the HNF1A gene. It is possible that in Iran, other yet to be
      identified genes are responsible for the familial young onset diabetes. Hence,
      there is a need for more extensive genetic analyses in Iranian patients with
      familial young onset diabetes.

PMID- 29371777
TI  - Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with
      Susceptibility to Rheumatoid Arthritis in Egyptian Population.
AB  - Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444
      polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to
      investigate association of mir-499 rs3746444 polymorphism with RA activity and
      severity in Egyptian population. The study population was conducted as case
      control study in 100 RA patients diagnosed according to the American College of
      Rheumatology classification criteria for RA, and the control group included 100
      healthy subjects who were age-and sex-matched to the RA group. Different
      genotypes were assessed using polymerase chain reaction-restriction fragment
      length polymorphism. 95% Confidence interval and odds ratio were defined to
      assess the strength of association. Regarding patients, thirty-three patients
      carried TT genotype, fifty-three patients carried TC genotype and fourteen
      patients carried CC genotype. So the frequency of the minor C allele in RA
      patients was significantly higher than the control subjects (P = 0.037). TC, CC
      genotypes and C allele frequencies were significantly associated with disease
      severity as they had high rheumatoid factor (55.78 uIU/ml) and anti-cyclic
      citrullinated peptide (Anti-CCP) antibody (297.32 uIU/ml). Moreover, the
      heterozygote TC had more severe and more active form of the disease compared with
      homozygote CC or TT as they had high Anti-CCP antibody, and disease activity
      score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444
      polymorphism contributes to heritability of susceptibility to RA compared to T
      allele. This polymorphism was associated with the activity and severity of the
      disease.

PMID- 29371778
TI  - Evaluation of Preanalytical Quality Indicators by Six Sigma and Pareto's
      Principle.
AB  - Preanalytical steps are the major sources of error in clinical laboratory. The
      analytical errors can be corrected by quality control procedures but there is a
      need for stringent quality checks in preanalytical area as these processes are
      done outside the laboratory. Sigma value depicts the performance of laboratory
      and its quality measures. Hence in the present study six sigma and Pareto
      principle was applied to preanalytical quality indicators to evaluate the
      clinical biochemistry laboratory performance. This observational study was
      carried out for a period of 1 year from November 2015-2016. A total of 1,44,208
      samples and 54,265 test requisition forms were screened for preanalytical errors
      like missing patient information, sample collection details in forms and
      hemolysed, lipemic, inappropriate, insufficient samples and total number of
      errors were calculated and converted into defects per million and sigma scale.
      Pareto's chart was drawn using total number of errors and cumulative percentage.
      In 75% test requisition forms diagnosis was not mentioned and sigma value of 0.9
      was obtained and for other errors like sample receiving time, stat and type of
      sample sigma values were 2.9, 2.6, and 2.8 respectively. For insufficient sample
      and improper ratio of blood to anticoagulant sigma value was 4.3. Pareto's chart
      depicts out of 80% of errors in requisition forms, 20% is contributed by missing
      information like diagnosis. The development of quality indicators, application of
      six sigma and Pareto's principle are quality measures by which not only
      preanalytical, the total testing process can be improved.

PMID- 29371779
TI  - Hyperferritinemia in Hemophagocytic Lymphohistiocytosis: A Single Institution
      Experience in Pediatric Patients.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition that may
      run a rapid fatal course and calls for prompt diagnosis. Early intervention with
      steroids and other immunosuppressive drugs can contain the disease process and
      favours positive outcome. Ferritin >=500 ng/ml is a HLH diagnostic criterion. We
      evaluated the diagnostic potential of admission ferritin, in children with HLH.
      Pediatric patients of a referral teaching hospital from Feb 2010-Oct 2013 having
      been investigated for ferritin on admission were included. HLH was confirmed when
      patients had clinical features and met 5/8 diagnostic criteria of the revised
      2004 HLH guidelines. Ferritin was estimated on Cobas e411 by
      electrochemiluminiscence, with a measuring range of 0.5-2000 ng/ml. Dilutions
      were made when linearity exceeded and absolute values were reported. 905 on
      admission ferritin investigations were reviewed out of which 346 values >=500
      ng/ml. Hyperferritinemia was seen in HLH/MAS (macrophage activation syndrome)
      [HLH group, median age 4 year 4 month, 59% male] and in systemic lupus
      erythematosus, sepsis, juvenile idiopathic arthritis, impending HLH, haemolytic
      anemias and malignancy [non-HLH group, median age 4 year 6 month, 60% male]. Of
      346, 72 cases of hyperferritinemia were diagnosed with secondary HLH while one
      patient had primary HLH. 13/73 patients expired. The median ferritin level of the
      HLH group was significantly higher [6556 (2402-11,734) ng/ml] compared to non-HLH
      group [median 1175 (943-2000) ng/ml] (p < 0.0001). Receiver operator
      characteristics curve analysis revealed optimal admission ferritin of 3120 ng/ml
      as the cut-off with sensitivity of 70% and specificity of 88.9% for HLH
      diagnosis, exceeding the currently prescribed cut-off of 500 ng/ml.
      Hyperferritinemia below 3120 ng/ml has higher negative predictive value to rule
      out secondary HLH on admission in the study population of children predominantly
      diagnosed with infection associated HLH than the prescribed cut-off as per the
      2004 guidelines. This may prove to be beneficial to alert physicians for prompt
      intervention which considerably decreases mortality in this often fatal
      condition.

PMID- 29371780
TI  - Cinderella in Serum Protein Electrophoresis.
AB  - Paraproteinemia is characterised by clonal proliferation of plasma cells. A
      common laboratory finding in paraproteinemia being a monoclonal peak in serum
      protein electrophoresis (M band). But there are factors which produce a peak
      similar to M spike in serum protein electrophoresis and these factors are known
      as pseudoparaproteins. This case report discusses a rare cause of pseudo M spike
      in a known case of autoimmune hemolytic anaemia due to administration of drug
      Rituximab, a monoclonal antibody by itself.

PMID- 29371781
TI  - A Proposed Method for Identification of Streptomycin Resistance from 16s rRNA
      Sequence by Co-localization Analysis of Fluorescent Signals: A Step Towards
      Detection of Streptomycin Resistant Mycobacterium Species in Culture Free and
      Gene Amplification Independent Technique.

PMID- 29371784
TI  - The Reproductive Morphology and Physiological Age Grading of the Female Salvinia
      Weevil, Cyrtobagous salviniae Calder and Sands.
AB  - The morphology of the female Cyrtobagous salviniae Calder and Sands reproductive
      system is similar to other weevil species being meroistic and telotrophic. The
      reproductive system is composed of 2 ovaries each containing 2 ovarioles where
      the follicles mature. A physiological age grading system was developed where the
      continuum of ovarium development was divided into 2 nulliparous and 3 parous
      classes. This was based on the differentiation of the ovarioles, presence, and
      appearance of follicular relics, cuticle hardness/coloration, and fat body
      quantity/appearance. High correlation occurred between the parous classes and
      number of eggs produced where the P3 class had over 9-fold higher number of eggs
      in comparison with the P1 class. Mean number of eggs produced for each parous
      class was significantly different, however, overlap occurred. Such a system
      enables a determination of the past, present, and future reproductive status of
      field populations and mass-rearing colonies.

PMID- 29371783
TI  - Evaluation of a Serum Lung Cancer Biomarker Panel.
AB  - Background: A panel of 3 serum proteins and 1 autoantibody has been developed to
      assist with the detection of lung cancer. We aimed to validate the accuracy of
      the biomarker panel in an independent test set and explore the impact of adding a
      fourth serum protein to the panel, as well as the impact of combining molecular
      and clinical variables. Methods: The training set of serum samples was purchased
      from commercially available biorepositories. The testing set was from a
      biorepository at the Cleveland Clinic. All lung cancer and control subjects were
      >50 years old and had smoked a minimum of 20 pack-years. A panel of biomarkers
      including CEA (carcinoembryonic antigen), CYFRA21-1 (cytokeratin-19 fragment 21
      1), CA125 (carbohydrate antigen 125), HGF (hepatocyte growth factor), and NY-ESO
      1 (New York esophageal cancer-1 antibody) was measured using immunoassay
      techniques. The multiple of the median method, multivariate logistic regression,
      and random forest modeling was used to analyze the results. Results: The training
      set consisted of 604 patient samples (268 with lung cancer and 336 controls) and
      the testing set of 400 patient samples (155 with lung cancer and 245 controls).
      With a threshold established from the training set, the sensitivity and
      specificity of both the 4- and 5-biomarker panels on the testing set was 49% and
      96%, respectively. Models built on the testing set using only clinical variables
      had an area under the receiver operating characteristic curve of 0.68, using the
      biomarker panel 0.81 and by combining clinical and biomarker variables 0.86.
      Conclusions: This study validates the accuracy of a panel of proteins and an
      autoantibody in a population relevant to lung cancer detection and suggests a
      benefit to combining clinical features with the biomarker results.

PMID- 29371782
TI  - A Single Electrochemical Probe Used for Analysis of Multiple Nucleic Acid
      Sequences.
AB  - Electrochemical hybridization sensors have been explored extensively for analysis
      of specific nucleic acids. However, commercialization of the platform is hindered
      by the need for attachment of separate oligonucleotide probes complementary to a
      RNA or DNA target to an electrode's surface. Here we demonstrate that a single
      probe can be used to analyze several nucleic acid targets with high selectivity
      and low cost. The universal electrochemical four-way junction (4J)-forming (UE4J)
      sensor consists of a universal DNA stem-loop (USL) probe attached to the
      electrode's surface and two adaptor strands (m and f) which hybridize to the USL
      probe and the analyte to form a 4J associate. The m adaptor strand was conjugated
      with a methylene blue redox marker for signal ON sensing and monitored using
      square wave voltammetry. We demonstrated that a single sensor can be used for
      detection of several different DNA/RNA sequences and can be regenerated in 30
      seconds by a simple water rinse. The UE4J sensor enables a high selectivity by
      recognition of a single base substitution, even at room temperature. The UE4J
      sensor opens a venue for a re-useable universal platform that can be adopted at
      low cost for the analysis of DNA or RNA targets.

PMID- 29371785
TI  - A Preliminary Evaluation of the Ability of Keratotic Tissue to Act as a
      Prognostic Indicator of Hip Fracture Risk.
AB  - Studies have shown that Raman spectroscopic analysis of fingernail clippings can
      help differentiate between post-menopausal women who have and who have not
      suffered a fracture. However, all studies to date have been retrospective in
      nature, comparing the proteins in nails sourced from women, post-fracture. The
      objective of this study was to investigate the potential of a prospective test
      for hip fracture based on spectroscopic analysis of nail tissue. Archived toenail
      samples from post-menopausal women aged 50 to 63 years in the Nurses' Health
      Study were obtained and analysed by Raman spectroscopy. Nails were matched case
      controls sourced from 161 women; 82 who underwent a hip fracture up to 20 years
      after nail collection and 81 age-matched controls. A number of clinical risk
      factors (CRFs) from the Fracture Risk Assessment (FRAX) tool had been assessed at
      toenail collection. Using 80% of the spectra, models were developed for
      increasing time periods between nail collection and fracture. Scores were
      calculated from these models for the other 20% of the sample and the ability of
      the score to predict hip fracture was tested in model with and without the CRFs
      by comparing the odds ratios (ORs) per 1 SD increase in standardised predictive
      values. The Raman score successfully distinguished between hip fracture cases and
      controls. With only the score as a predictor, a statistically significant OR of
      2.2 (95% confidence interval [CI]: 1.5-3.1) was found for hip fracture for up to
      20 years after collection. The OR increased to 3.8 (2.6-5.4) when the CRFs were
      added to the model. For fractures limited to 13 years after collection, the OR
      was 6.3 (3.0-13.1) for the score alone. The test based on Raman spectroscopy has
      potential for identifying individuals who may suffer hip fractures several years
      in advance. Higher powered studies are required to evaluate the predictive
      capability of this test.

PMID- 29371786
TI  - Total Knee Arthroplasty: Does Day of Surgery Matter?
AB  - Introduction: There has been an influx of research studies aimed at identifying
      all factors that contribute to minimizing cost and maximizing postoperative care
      after total knee arthroplasty (TKA). Length of stay (LOS) has been defined as a
      significant factor that contributes to increased burden. We aimed at looking
      whether day of surgery has any significant effect on the LOS and postoperative
      complications following total knee arthroplasty (TKA). Materials and methods:
      Retrospective cohort study done at the Aga Khan University Hospital, Pakistan,
      from January 2007 to December 2015. A total of 611 patients who underwent a
      unilateral or bilateral total knee arthroplasty (TKA) were included in study: 269
      (44.0%) patients underwent unilateral TKA and 342 (56.0%) underwent a bilateral
      TKA. Results: Kruskal-Wallis test and post hoc pairwise comparisons showed that
      unilateral TKAs performed on Tuesday, Saturday, and Sunday resulted in a lower
      median LOS (P < .05). No significant association was seen in bilateral TKA group.
      Day of surgery was not associated with postoperative complications. Conclusions:
      Unilateral TKAs performed earlier during the week and later on the weekend are
      associated with a significantly lower LOS. It is highly probable that patch
      ancillary services during the latter part of the week and a higher workload for
      the staff are important reasons for this phenomenon.

PMID- 29371788
TI  - Awareness of 'Systolic Anterior Motion' in Different Conditions.
AB  - Perioperative echocardiography, especially transesophageal echocardiography, is
      of paramount importance in evaluating and managing refractory hypotension, a
      potential cause of which is systolic anterior motion (SAM) of anterior mitral
      leaflet. Dynamically moving anterior mitral valve leaflet towards the left
      ventricular outflow tract (LVOT) is described as SAM. Although SAM was initially
      observed in patients with hypertrophic cardiomyopathy, it can also be seen in
      patients with complex dynamic anatomy of the left ventricle. Interestingly, SAM
      may or may not give rise to clinically significant LVOT obstruction. Hence, it is
      of paramount importance for perioperative physician to know such 'dynamic SAM'
      which can potentially and significantly affect and alter perioperative
      management.

PMID- 29371787
TI  - Preeclampsia: From Inflammation to Immunoregulation.
AB  - Preeclampsia (PE) affects 5% to 7% of pregnant women each year worldwide,
      accounts for up to 18% of maternal deaths in the United States each year, and is
      the number 1 cause of premature births. Preeclampsia is associated with
      hypertension after the 20th week of gestation with or without proteinuria, in
      conjunction with fetal growth restriction, maternal endothelial dysfunction, and
      chronic immune activation. The mechanisms leading to the development of PE are
      unclear. However, it is thought that shallow trophoblast invasion and
      insufficient remodeling of uterine spiral arteries result in placental ischemia.
      Consequently, an immune imbalance characterized by increases in proinflammatory
      CD4+ T cells and cytokines along with decreases in regulatory T cells and anti
      inflammatory cytokines occurs. This imbalance leads to chronic inflammation and
      ensuing oxidative stress, proinflammatory cytokines, and autoantibodies. Studies
      performed in our laboratories, using the Reduced Uterine Perfusion Pressure
      (RUPP) rat model of placental ischemia, have demonstrated a role for this immune
      imbalance to mediate PE pathophysiology and identified potential mechanisms of
      immunoregulation that may be of benefit in the treatment of PE. Therefore, the
      purpose of this commentary is to review studies demonstrating the positive
      effects of immunoregulatory factors in the RUPP rat model of PE. Restoration of
      the immune balance in PE may be a potential strategy for the development of
      therapeutic interventions that could improve maternal and fetal outcomes
      associated with this maternal syndrome.

PMID- 29371789
TI  - Case Report of a Small Gastric Neuroendocrine Tumor in a Deep Layer of Submucosa
      With Diagnosis by Endoscopic Ultrasound-Guided Fine-Needle Aspiration and
      Treatment With Laparoscopic and Endoscopic Cooperative Surgery.
AB  - Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by
      enterochromaffin-like cells of the stomach. Optimal management of GNETs has not
      yet been definitively determined. Endoscopic resection is approximately
      recommended for small GNETs associated with hypergastrinemia. However, endoscopic
      resection might present risk of perforation or positive vertical margin because
      neuroendocrine tumors occur in the deep mucosa, with some invading the submucosa.
      In this case, a patient with type A chronic atrophic gastritis had a small
      subepithelial lesion in a deep submucosal layer, and we diagnosed it as GNET
      using endoscopic ultrasound-guided fine-needle aspiration biopsy using a forward
      viewing and curved linear-array echoendoscope. Moreover, our results show that
      laparoscopic and endoscopic cooperative surgery with regional lymph node
      dissection is a safe and feasible procedure for GNETs, especially those that
      cross to the muscularis propria. We suggest this approach as one therapeutic
      option for GNETs because it safely minimizes resection and is less invasive.

PMID- 29371790
TI  - Crizotinib, an Effective Agent in ROS1-Rearranged Adenocarcinoma of Lungs: A Case
      Report.
AB  - Introduction: ROS1 rearrangement has recently emerged as a new molecular subtype
      in non-small-cell lung cancer (NSCLC) and is predominantly found in lung
      adenocarcinoma compared with other oncogenes such as EGFR, KRAS, or ALK. It has
      been identified in only 1% to 2% of NSCLC cases. Case Report: We report a case of
      52-year-old man (nonsmoker) with a medical history of allergic rhinitis and
      bronchial asthma. Histopathologic examination of bronchoscopic-guided biopsy
      showed adenocarcinoma histology on September 2015. After 2 months, he developed
      left-sided pneumonia for which he was treated with multiple intravenous
      antibiotics. In the meantime, fiberoptic bronchoscopy was done which revealed
      purulent secretion from right upper lobe and narrowed opening of right middle
      lobe. His cancer symptoms got worsened and bronchial biopsy showed EGFR mutation
      negative. For further diagnosis, fluorescent in situ hybridization test was done
      which showed ROS1 mutation positive. By then, the patient was started with
      crizotinib 250 mg twice daily for ROS1 mutation in July 2016. Later, patient
      appears to benefit from treatment with crizotinib. X-ray report and positron
      emission tomographic-computed tomographic scan revealed that the patient was
      overall better with clear chest and well tolerated with the therapy. Crizotinib
      was approved on March 11, 2016 by Food and Drug Administration for the treatment
      of patients with ROS1-positive NSCLC. Conclusions: In this report, crizotinib
      showed marked antitumor activity in patients with advanced ROS1 rearrangement, a
      third molecular subgroup of NSCLC.

PMID- 29371791
TI  - Drosophila melanogaster as a Model for Studying Aspergillus fumigatus.
AB  - Drosophila melanogaster is a useful model organism that offers essential insights
      into developmental and cellular processes shared with humans, which has been
      adapted for large scale analysis of medically important microbes and to test the
      toxicity of heavy metals, industrial solvents and other poisonous substances. We
      here give a brief review of the use of the Drosophila model in medical mycology,
      discuss the volatile organic compounds (VOCs) produced by the opportunistic human
      pathogen, Aspergillus fumigatus, and give a brief summary of what is known about
      the toxicity of some common fungal VOCs. Further, we discuss the use of VOC
      detection as an indirect indicator of fungal growth, including for early
      diagnosis of aspergillosis. Finally, we hypothesize that D. melanogaster has
      promise for investigating the role of VOCs synthesized by A. fumigatus as
      possible virulence factors.

PMID- 29371793
TI  - Arthothelium punctatum (Arthoniaceae, Arthoniales), A New Lichen Species from
      South Korea.
AB  - A total of 121 species of lichens belonging to the genus Arthothelium have been
      described to date, most of which have been found in tropical regions. Here, we
      describe the discovery of a novel Arthothelium species for the first time in
      South Korea. Until now, Arthothelium ruanum was the only Arthothelium species
      reported in South Korea. Among the 113 specimens collected in this study, we
      identified A. ruanum and a putative new species, Arthothelium punctatum (J. S.
      Park & J.-S. Hur, sp. nov.). The diagnostic characters of A. punctatum are as
      follows: apothecia punctate, shortly elongate to branched, small, 0.1-0.2 mm
      wide, hypothecium hyaline to pale brown and obovate to broadly ellipsoid,
      muriform ascospores, 29.5-44.6 * 12.2-18.2 MUm. The new species was found in Mt.
      Seokbyeong at an altitude of 790 m on smooth bark. Upon phylogenic analysis, the
      putative new species, A. punctatum, was separated from other Arthothelium species
      although the specimens analyzed were clustered with Arthoniaceae in phylogenetic
      trees based on both the mitochondrial small subunit (mtSSU) sequence and combined
      mtSSU and nuclear ribosomal large subunit sequences. Our data clearly indicate
      that this species is a new species belonging to the family Arthoniaceae. To
      elucidate the taxonomic characteristics of the new species, we provide
      morphological descriptions and a distribution map.

PMID- 29371792
TI  - Influence of Temperature and Water Activity on Deleterious Fungi and Mycotoxin
      Production during Grain Storage.
AB  - Cereal grains are the most important food source for humans. As the global
      population continues to grow exponentially, the need for the enhanced yield and
      minimal loss of agricultural crops, mainly cereal grains, is increasing. In
      general, harvested grains are stored for specific time periods to guarantee their
      continuous supply throughout the year. During storage, economic losses due to
      reduction in quality and quantity of grains can become very significant. Grain
      loss is usually the result of its deterioration due to fungal contamination that
      can occur from preharvest to postharvest stages. The deleterious fungi can be
      classified based on predominance at different stages of crop growth and harvest
      that are affected by environmental factors such as water activity (aw) and eco
      physiological requirements. These fungi include species such as those belonging
      to the genera Aspergillus and Penicillium that can produce mycotoxins harmful to
      animals and humans. The grain type and condition, environment, and biological
      factors can also influence the occurrence and predominance of mycotoxigenic fungi
      in stored grains. The main environmental factors influencing grain fungi and
      mycotoxins are temperature and aw. This review discusses the effects of
      temperature and aw on fungal growth and mycotoxin production in stored grains.
      The focus is on the occurrence and optimum and minimum growth requirements for
      grain fungi and mycotoxin production. The environmental influence on aflatoxin
      production and hypothesized mechanisms of its molecular suppression in response
      to environmental changes are also discussed. In addition, the use of controlled
      or modified atmosphere as an environmentally safe alternative to harmful
      agricultural chemicals is discussed and recommended future research issues are
      highlighted.

PMID- 29371794
TI  - Taxonomy and Phylogeny of Peronospora Species (Oomycota) Parasitic to Stellaria
      and Pseudostellaria in Korea, with the Introduction of Peronospora casparyi sp.
      nov.
AB  - The genus Peronospora, an obligate biotrophic group belonging to Oomycota, causes
      serious damage to a variety of wild and ornamental plants, as well as cultivated
      crops, such as beet, rose, spinach, and tobacco. To investigate the diversity of
      Peronospora species parasitic to Stellaria and Pseudostellaria (Caryophyllaceae)
      plants in Korea, we performed a morphological analysis on dried herbarium
      specimens and molecular phylogenetic inferences based on internal transcribed
      spacer rDNA and cox2 mitochondrial DNA sequences. As a result, it was confirmed
      that there are four species of Peronospora parasitic to specific species of
      Stellaria and Pseudostellaria, all of which were hitherto unrecorded in Korea: P.
      alsinearum (ex Stellaria media), P. stellariae-aquaticae (ex Stellaria aquatica),
      P. stellariae-uliginosae (ex Stellaria alsine), and P. pseudostellariae (ex
      Pseudostellaria palibiniana). In addition, Peronospora specimens parasitic to
      Pseudostellaria davidii differed morphologically from P. pseudostellariae owing
      to the large and ellipsoidal conidia; this morphological discrepancy was also
      validated by the high genetic divergence between the two species. Peronospora
      casparyi sp. nov. is described and illustrated here.

PMID- 29371795
TI  - Taxonomic Revision of the Lichen Genera Pertusaria, Varicellaria, and Variolaria
      (Pertusariales, Ascomycota) in South Korea.
AB  - The crustose lichen genus Pertusaria comprises over ca. 800 species worldwide. In
      total, 20 Pertusaria species were localized to the Mt. Sorak and Jeju-do in
      Korea. To date, information regarding the distribution of Pertusaria species in
      the South Korean peninsula is scarce. In this study, we collected Pertusaria
      species across South Korea and identified them based on morphological, chemical,
      and molecular characteristics. Of the 387 samples collected, we identified 24
      taxa and 1 variety, of which 17 were previously recorded, and 6 taxa were newly
      found in South Korea (P. leioplaca, P. leucosora var. violascens, P. texana, P.
      thiospoda, P. thwaitesii, and P. xanthodes), 2 known species were transferred to
      Varicellaria (Varicellaria lactea and V. velata), one species was transferred to
      Variolaria as a new record (Variolaria multipunctoides) and one was a new species
      (P. jogyeensis J. S. Park & J.-S. Hur, sp. nov.). Characteristics of the newly
      discovered species, P. jogyeensis, are as follows: smooth to bumpy thallus,
      scattered to crowded poriform apothecia, blackish ostioles, definitely sunken,
      thin yellowish green rims around ostioles, 8-spored ascus, and the presence of
      perlatolic acid and thiophaninic acid (chlorinated xanthone). Phylogenetic
      studies on P. jogyeensis based on the mitochondrial small subunit sequence
      revealed proximity to P. flavicans and P. texana, and supported its
      classification as a new species within the genus Pertusaria. Additionally, we
      describe the chemical composition and morphology of all listed species in detail
      and provide an artificial key for identification.

PMID- 29371796
TI  - Ten New Recorded Species of Macrofungi on Ulleung Island, Korea.
AB  - Ulleung Island is a biodiversity hotspot in South Korea. During a survey of
      indigenous fungal species from Ulleung Island conducted from 2015 to 2016, we
      discovered 10 unrecorded macrofungi in Korea. These macrofungi were identified to
      the species level using morphological features and phylogenetic analysis based on
      the internal transcribed spacer region: Deconica phyllogena, Mycena zephirus,
      Phaeomarasmius proximans, Phlebia radiata, Pluteus semibulbosus, Postia alni,
      Resinicium pinicola, Scytinostroma portentosum, Tricholomopsis flammula, and
      Tyromyces kmetii. We also provide detailed morphological descriptions for these
      10 species.

PMID- 29371797
TI  - Saprolegnia parasitica Isolated from Rainbow Trout in Korea: Characterization,
      Anti-Saprolegnia Activity and Host Pathogen Interaction in Zebrafish Disease
      Model.
AB  - Saprolegniasis is one of the most devastating oomycete diseases in freshwater
      fish which is caused by species in the genus Saprolegnia including Saprolegnia
      parasitica. In this study, we isolated the strain of S. parasitica from diseased
      rainbow trout in Korea. Morphological and molecular based identification
      confirmed that isolated oomycete belongs to the member of S. parasitica,
      supported by its typical features including cotton-like mycelium, zoospores and
      phylogenetic analysis with internal transcribed spacer region. Pathogenicity of
      isolated S. parasitica was developed in embryo, juvenile, and adult zebrafish as
      a disease model. Host-pathogen interaction in adult zebrafish was investigated at
      transcriptional level. Upon infection with S. parasitica, pathogen/antigen
      recognition and signaling (TLR2, TLR4b, TLR5b, NOD1, and major histocompatibility
      complex class I), pro/anti-inflammatory cytokines (interleukin [IL]-1beta, tumor
      necrosis factor alpha, IL-6, IL-8, interferon gamma, IL-12, and IL-10), matrix
      metalloproteinase (MMP9 and MMP13), cell surface molecules (CD8+ and CD4+) and
      antioxidant enzymes (superoxide dismutase, catalase) related genes were
      differentially modulated at 3- and 12-hr post infection. As an anti-Saprolegnia
      agent, plant based lawsone was applied to investigate on the susceptibility of S.
      parasitica showing the minimum inhibitory concentration and percentage inhibition
      of radial growth as 200 MUg/mL and 31.8%, respectively. Moreover, natural lawsone
      changed the membrane permeability of S. parasitica mycelium and caused
      irreversible damage and disintegration to the cellular membranes of S.
      parasitica. Transcriptional responses of the genes of S. parasitica mycelium
      exposed to lawsone were altered, indicating that lawsone could be a potential
      anti-S. parasitica agent for controlling S. parasitica infection.

PMID- 29371798
TI  - Differences among Endophytic Fungal Communities Isolated from the Roots of
      Cephalanthera longibracteata Collected from Different Sites in Korea.
AB  - Orchidaceous plants have symbiotic relationships with endophytic fungi, including
      mycorrhizal fungi, which play important roles in the seed germination and growth
      of the host plants. In this study, endophytic fungal communities isolated from
      the roots of Cephalanthera longibracteata collected from three different sites in
      Korea were analyzed, and it was determined whether fungal communities were
      preferentially correlated with the sites. The fungal isolates were identified by
      sequence analysis of the internal transcribed spacer regions of rDNA. In total,
      30 species of endophytic fungi, including two species of mycorrhizal fungi
      belonging to the genus Tulasnella, were identified. Leptodontidium orchidicola
      showed the highest frequency and was isolated from all root samples. Species
      diversity and richness were not significantly different among sites. However, the
      community structure of the endophytic fungi significantly differed among sites,
      suggesting that the site characteristics affected the community composition of
      the endophytic fungi colonizing the roots of C. longibracteata. Our findings will
      aid in developing methods involving the use of symbiotic fungi for orchid
      conservation and restoration in native habitats.

PMID- 29371799
TI  - Isolation and Characterization of Three Unrecorded Zygomycete Fungi in Korea:
      Cunninghamella bertholletiae, Cunninghamella echinulata, and Cunninghamella
      elegans.
AB  - In a survey of undiscovered taxa in Korea, three zygomycete fungal strains-EML
      W31, EML-HGD1-1, and EML-RUS1-1-were isolated from freshwater, grasshopper fecal,
      and soil samples in Korea. On the basis of the morphological characteristics and
      phylogenetic analysis of internal transcribed spacer and 28S rDNA, the isolates
      of EML-W31, EML-HGD1-1, and EML-RUS1-1 were confirmed to be Cunninghamella
      bertholletiae, Cunninghamella echinulata, and Cunninghamella elegans,
      respectively. These species have not been previously described in Korea.

PMID- 29371800
TI  - Three New Records of Ascomycetes Isolates from Field Soils in Korea.
AB  - Three new records of Ascomycota species (Chaetomium acropullum, Phialemonium
      globosum, Phialemonium atrogriseum) from field soils in Korea are presented in
      this study. These newly discovered fungal isolates were isolated from field soils
      from various places across Gyeongnam, Korea in 2016. All the isolates were
      identified and described based on morphological characteristics, and rDNA
      internal transcribed spacer and beta-tubulin gene sequence data. Morphological
      features of these fungal species were studied on different agar media: potato
      dextrose agar, oatmeal agar, malt extract agar, Czapek yeast extract agar, and
      yeast extract sucrose agar. Full description and illustrations of their
      morphological characters are provided. These fungal species have not officially
      been previously reported in Korea.

PMID- 29371801
TI  - Cryptothecia austrocoreana (Arthoniales, Arthoniaceae), a New Species from South
      Korea.
AB  - Cryptothecia austrocoreana is a new lichen species from South Korea. The species
      is characterized by the presence of a heteromerous thallus and faveolate
      ascigerous area (ascomata) immersed in a slightly raised thallus. The species has
      muriform ascospores, (4)6-8-spored 8-11 * 3-4 septate, (34)36-48(51) * (17)19
      23(25) MUm. Atranorin, chloroatranorin, and barbatic acid are present. In the
      phylogenetic tree, C. austrocoreana belongs to the arthonioid clade in
      Arthoniaceae.

PMID- 29371802
TI  - Phylogenetic Status of Two Undescribed Zygomycete Species from Korea: Actinomucor
      elegans and Mucor minutus.
AB  - During a survey of fungal diversity of the order Mucorales, three zygomycete
      isolates, CNUFC-YR113-1, CNUFC-KNU16-7, and CNUFC-BS1-1 were isolated from
      freshwater and soil samples in Korea. The strains were analyzed both
      morphologically and phylogenetically based on internal transcribed spacer and 28S
      rDNA gene sequences. Based on their morphology and phylogeny, the CNUFC-YR113-1
      and CNUFC-KNU16-7 isolates were identified as Actinomucor elegans, and CNUFC-BS1
      1 was identified as Mucor minutus. To the best of our knowledge, the species A.
      elegans and M. minutus, belonging to an undiscovered taxon, have not been
      previously described in Korea.

PMID- 29371803
TI  - Characterization of Two Species of Acremonium (Unrecorded in Korea) from Soil
      Samples: A. variecolor and A. persicinum.
AB  - During a survey of fungal diversity of the order Hypocreales in Korea, two
      Acremonium isolates, CNUFC-1YSRS2-4 and CNUFC-GSNPF3-1, were isolated from soils
      collected on a bank of the Yeongsan River, Naju, and in a forest on the Mt.
      Daegak located on Sinsi Island, Gunsan, South Korea, respectively. Based on the
      morphological characteristics and sequence analysis of the internal transcribed
      spacer and D1/D2 domains of 28S ribosomal DNA, the isolates CNUFC-1YSRS2-4 and
      CNUFC-GSNPF3-1 were identified as A. variecolor and A. persicinum, respectively.
      These 2 species represent novel Hypocreales isolates in Korea.

PMID- 29371804
TI  - Role of MAPK Signaling Pathways in Regulating the Hydrophobin Cryparin in the
      Chestnut Blight Fungus Cryphonectria parasitica.
AB  - We assessed the regulation of cryparin, a class II hydrophobin, using three
      representative mitogen-activated protein kinase (MAPK) pathways in Cryphonectria
      parasitica. Mutation of the CpSlt2 gene, an ortholog of yeast SLT2 in the cell
      wall integrity (CWI) pathway, resulted in a dramatic decrease in cryparin
      production. Similarly, a mutant of the CpBck1 gene, a MAP kinase kinase kinase
      gene in the CWI pathway, showed decreased cryparin production. Additionally,
      mutation of the cpmk1 gene, an ortholog of yeast HOG1, showed decreased cryparin
      production. However, mutation of the cpmk2 gene, an ortholog of yeast Kss1/Fus3,
      showed increased cryparin production. The easy-wet phenotype and accumulation of
      the cryparin transcript in corresponding mutants were consistent with the
      cryparin production results. In silico analysis of the promoter region of the
      cryparin gene revealed the presence of binding motifs related to downstream
      transcription factors of CWI, HOG1, and pheromone responsive pathways including
      MADS-box- and Ste12-binding domains. Real-time reverse transcriptase PCR analyses
      indicated that both CpRlm1, an ortholog of yeast RLM1 in the CWI pathway, and
      cpst12, an ortholog of yeast STE12 in the mating pathway, showed significantly
      reduced transcription levels in the mutant strains showing lower cryparin
      production in C. prasitica. However, the transcription of CpMcm1, an ortholog of
      yeast MCM1, did not correlate with that of the mutant strains showing
      downregulation of cryparin. These results indicate that three representative MAPK
      pathways played a role in regulating cryparin production. However, regulation
      varied depending on the MAPK pathways: the CWI and HOG1 pathways were
      stimulatory, whereas the pheromone-responsive MAPK was repressive.

PMID- 29371805
TI  - Antagonistic Evaluation of Chromobacterium sp. JH7 for Biological Control of
      Ginseng Root Rot Caused by Cylindrocarpon destructans.
AB  - Cylindrocarpon destructans is an ascomycete soil-borne pathogen that causes
      ginseng root rot. To identify effective biocontrol agents, we isolated several
      bacteria from ginseng cultivation soil and evaluated their antifungal activity.
      Among the isolated bacteria, one isolate (named JH7) was selected for its high
      antibiotic activity and was further examined for antagonism against fungal
      pathogens. Strain JH7 was identified as a Chromobacterium sp. using phylogenetic
      analysis based on 16S rRNA gene sequences. This strain was shown to produce
      antimicrobial molecules, including chitinases and proteases, but not cellulases.
      Additionally, the ability of JH7 to produce siderophore and solubilize insoluble
      phosphate supports its antagonistic and beneficial traits for plant growth. The
      JH7 strain suppressed the conidiation, conidial germination, and chlamydospore
      formation of C. destructans. Furthermore, the JH7 strain inhibited other plant
      pathogenic fungi. Thus, it provides a basis for developing a biocontrol agent for
      ginseng cultivation.

PMID- 29371806
TI  - Nucleus-Selective Expression of Laccase Genes in the Dikaryotic Strain of
      Lentinula edodes.
AB  - In mating of Lentinula edodes, dikaryotic strains generated from certain
      monokaryotic strains such as the B2 used in this study tend to show better
      quality of fruiting bodies regardless of the mated monokaryotic strains. Unlike
      B2, dikaryotic strains generated from B16 generally show low yields, with
      deformed or underdeveloped fruiting bodies. This indicates that the two nuclei in
      the cytoplasm do not contribute equally to the physiology of dikaryotic L.
      edodes, suggesting an expression bias in the allelic genes of the two nuclei. To
      understand the role of each nucleus in dikaryotic strains, we investigated single
      nucleotide polymorphisms (SNPs) in laccase genes of monokaryotic strains to
      reveal nuclear origin of the expressed mRNAs in dikaryotic strain. We performed
      reverse transcription PCR (RT-PCR) analysis using total RNAs extracted from
      dikaryotic strains (A5B2, A18B2, and A2B16) as well as from compatible
      monokaryotic strains (A5, A18, and B2 for A5B2 and A18B2; A2 and B16 for A2B16).
      RT-PCR results revealed that Lcc1, Lcc2, Lcc4, Lcc7, and Lcc10 were the mainly
      expressed laccase genes in the L. edodes genome. To determine the nuclear origin
      of these laccase genes, the genomic DNA sequences in monokaryotic strains were
      analyzed, thereby revealing five SNPs in Lcc4 and two in Lcc7. Subsequent
      sequence analysis of laccase mRNAs expressed in dikaryotic strains revealed that
      these were almost exclusively expressed from B2-originated nuclei in A5B2 and
      A18B2 whereas B16 nucleus did not contribute to laccase expression in A2B16
      strain. This suggests that B2 nucleus dominates the expression of allelic genes,
      thereby governing the physiology of dikaryons.

PMID- 29371807
TI  - Antifungical Activity of Autochthonous Bacillus subtilis Isolated from Prosopis
      juliflora against Phytopathogenic Fungi.
AB  - The ability of Bacillus subtilis, strain ALICA to produce three mycolytic enzymes
      (chitinase, beta-1,3-glucanase, and protease), was carried out by the chemical
      standard methods. Bacillus subtilis ALICA was screened based on their antifungal
      activity in dual plate assay and cell-free culture filtrate (25%) against five
      different phytopathogenic fungi Alternaria alternata, Macrophomina sp.,
      Colletotrichum gloeosporioides, Botrytis cinerea, and Sclerotium rolfesii. The B.
      subtilis ALICA detected positive for chitinase, beta-1,3-glucanase and protease
      enzymes. Fungal growth inhibition by both strain ALICA and its cell-free culture
      filtrate ranged from 51.36% to 86.3% and 38.43% to 68.6%, respectively. Moreover,
      hyphal morphological changes like damage, broken, swelling, distortions abnormal
      morphology were observed. Genes expression of protease, beta-1,3-glucanase, and
      lipopeptides (subtilosin and subtilisin) were confirmed their presence in the
      supernatant of strain ALICA. Our findings indicated that strain ALICA provided a
      broad spectrum of antifungal activities against various phytopathogenic fungi and
      may be a potential effective alternative to chemical fungicides.

PMID- 29371808
TI  - Influence of Peanut Cultivars and Environmental Conditions on the Diversity and
      Community Composition of Pod Rot Soil Fungi in China.
AB  - Peanut yield and quality are seriously affected by pod rot pathogens worldwide,
      especially in China in recent years. The goals of this study are to analyze the
      structure of fungal communities of peanut pod rot in soil in three peanut
      cultivars and the correlation of pod rot with environmental variables using 454
      pyrosequencing. A total of 46,723 internal transcribed spacer high-quality
      sequences were obtained and grouped into 1,706 operational taxonomic units at the
      97% similarity cut-off level. The coverage, rank abundance, and the Chao 1 and
      Shannon diversity indices of the operational taxonomic units were analyzed.
      Members of the phylum Ascomycota were dominant, such as Fusarium, Chaetomium,
      Alternaria, and Sordariomycetes, followed by Basidiomycota. The results of the
      heatmap and redundancy analysis revealed significant variation in the composition
      of the fungal community among the three cultivar samples. The environmental
      conditions in different peanut cultivars may also influence on the structure of
      the fungal community. The results of this study suggest that the causal agent of
      peanut pod rot may be more complex, and cultivars and environmental conditions
      are both important contributors to the community structure of peanut pod rot
      fungi.

PMID- 29371809
TI  - Development of a High-Resolution Multi-Locus Microsatellite Typing Method for
      Colletotrichum gloeosporioides.
AB  - Colletotrichum gloeosporioides is an economically important fungal pathogen
      causing substantial yield losses indifferent host plants. To understand the
      genetic diversity and molecular epidemiology of this fungus, we have developed a
      novel, high-resolution multi-locus microsatellite typing (MLMT) method.
      Bioinformatic analysis of C. gloeosporioides unannotated genome sequence yielded
      eight potential microsatellite loci, of which five, CG1 (GT)n, CG2 (GT1)n, CG3
      (TC)n, CG4 (CT)n, and CG5 (CT1)n were selected for further study based on their
      universal amplification potential, reproducibility, and repeat number
      polymorphism. The selected microsatellites were used to analyze 31 strains of C.
      gloeosporioides isolated from 20 different host plants from India. All
      microsatellite loci were found to be polymorphic, and the approximate fragment
      sizes of microsatellite loci CG1, CG2, CG3, CG4, and CG5 were in ranges of 213
      241, 197-227, 231-265, 209-275, and 132-188, respectively. Among the 31 isolates,
      55 different genotypes were identified. The Simpson's index of diversity (D)
      values for the individual locus ranged from 0.79 to 0.92, with the D value of all
      combined five microsatellite loci being 0.99. Microsatellite data analysis
      revealed that isolates from Ocimum sanctum, Capsicum annuum (chili pepper), and
      Mangifera indica (mango) formed distinct clusters, therefore exhibited some level
      of correlation between certain genotypes and host. The developed MLMT method
      would be a powerful tool for studying the genetic diversity and any possible
      genotype-host correlation in C. gloeosporioides.

PMID- 29371810
TI  - Induction of Defense-Related Physiological and Antioxidant Enzyme Response
      against Powdery Mildew Disease in Okra (Abelmoschus esculentus L.) Plant by Using
      Chitosan and Potassium Salts.
AB  - Foliar sprays of three plant resistance inducers, including chitosan (CH),
      potassium sorbate (PS) (C6H7kO2), and potassium bicarbonates (PB) (KHCO3), were
      used for resistance inducing against Erysiphe cichoracearum DC (powdery mildew)
      infecting okra plants. Experiments under green house and field conditions showed
      that, the powdery mildew disease severity was significantly reduced with all
      tested treatments of CH, PS, and PB in comparison with untreated control. CH at
      0.5% and 0.75% (w/v) plus PS at 1.0% and 2.0% and/or PB at 2.0% or 3.0% recorded
      as the most effective treatments. Moreover, the highest values of vegetative
      studies and yield were observed with such treatments. CH and potassium salts
      treatments reflected many compounds of defense singles which leading to the
      activation power defense system in okra plant. The highest records of reduction
      in powdery mildew were accompanied with increasing in total phenolic, protein
      content and increased the activity of polyphenol oxidase, peroxidase, chitinase,
      and beta-1,3-glucanase in okra plants. Meanwhile, single treatments of CH, PS,
      and PB at high concentration (0.75%, 2.0%, and/or 3.0%) caused considerable
      effects. Therefore, application of CH and potassium salts as natural and chemical
      inducers by foliar methods can be used to control of powdery mildew disease at
      early stages of growth and led to a maximum fruit yield in okra plants.

PMID- 29371811
TI  - Identification and Characterization of New Record of Grape Ripe Rot Disease
      Caused by Colletotrichum viniferum in Korea.
AB  - In 2016, grape fruits showing ripe rot symptom were found in fields of Korea. The
      fungus was isolated and identified as Colletotrichum viniferum based on
      morphological characteristics and nucleotide sequence data of the internal
      transcribed spacer, glyceraldehyde-3-phosphate dehydrogenase and beta-tubulin. To
      our knowledge, this is the first report of C. viniferum causing grape ripe rot
      disease of grape fruits in Korea.

PMID- 29371812
TI  - Azole Resistance Caused by Increased Drug Efflux in Candida glabrata Isolated
      from the Urinary Tract of a Dog with Diabetes Mellitus.
AB  - A yeast-like organism was isolated from a urine sample of a 6-year-old neutered
      male miniature poodle dog with urinary tract infection, diabetes ketoacidosis,
      and acute pancreatitis. We identified the yeast-like organism to be Candida
      glabrata and found that this fungus was highly resistant to azole antifungal
      drugs. To understand the mechanism of azole resistance in this isolate, the
      sequences and expression levels of the genes involved in drug resistance were
      analyzed. The results of our analysis showed that increased drug efflux, mediated
      by overexpression of ATP transporter genes CDR1 and PDH1, is the main cause of
      azole resistance of the C. glabrata isolated here.

PMID- 29371813
TI  - Two Endophytic Diaporthe Species Isolated from the Leaves of Astragalus
      membranaceus in Korea.
AB  - We characterized two endophyte fungi from the leaves of Astragalus membranaceus
      in Korea. The isolated strains were identified on the basis of the morphological
      characters and sequences analysis of the internal transcribed spacer and large
      subunit regions of the rDNA and beta-tubulin gene. To the best of our knowledge,
      this is the first report of Diaporthe oncostoma and Diaporthe infecunda in Korea,
      and we have provided descriptions and figures.

PMID- 29371814
TI  - An Improved Total RNA Extraction Method for White Jelly Mushroom Tremella
      fuciformis Rich in Polysaccharides.
AB  - An improved method for extracting high quality and quantity RNA from a jelly
      mushroom and a dimorphic fungus-Tremella fuciformis which is especially rich in
      polysaccharides, is described. RNA was extracted from T. fuciformis mycelium
      M1332 and its parental monokaryotic yeast-like cells Y13 and Y32. The A260/280
      and A260/230 ratios were both approximately 2, and the RNA integrity number was
      larger than 8.9. The yields of RNA were between 108 and 213 ug/g fresh wt.
      Downstream molecular applications including reverse transcriptional PCR and
      quantitative real-time PCR were also performed. This protocol is reliable and may
      be widely applicable for total RNA extraction from other jelly mushrooms or
      filamentous fungi rich in polysaccharides.

PMID- 29371815
TI  - Revolutionizing male fertility factor research in mice by using the genome
      editing tool CRISPR/Cas9.
AB  - Background: Reproductive research is quintessential in understanding not only the
      cause of infertility, but also for creating family planning tools. The knockout
      (KO) system approach is conducive to discovering genes that are essential for
      fertility in mice. However, in vivo research has been limited due to its high
      cost and length of time needed to establish KO mice. Methods: The mechanisms
      behind the CRISPR/Cas9 system and its application in investigating male fertility
      in mice are described by using original and review articles. Results: The
      CRISPR/CAS9 SYSTEM has enabled researchers to rapidly, efficiently, and
      inexpensively produce genetically modified mice to study male fertility. Several
      genes have been highlighted that were found to be indispensable for male
      fertility by using the CRISPR/Cas9 system, as well as more complicated gene
      manipulation techniques, such as point mutations, tag insertions, and double
      knockouts, which have become easier with this new technology. Conclusion: In
      order to increase efficiency and usage, new methods of CRISPR/Cas9 integration
      are being developed, such as electroporation and applying the system to embryonic
      stem cells. The hidden mysteries of male fertility will be unraveled with the
      help of this new technology.

PMID- 29371817
TI  - Assisted reproductive technology in Japan: a summary report for 2015 by The
      Ethics Committee of The Japan Society of Obstetrics and Gynecology.
AB  - Purpose: The Japan Society of Obstetrics and Gynecology (JSOG) implemented an
      assisted reproductive technology (ART) registry system in 1986. Here are reported
      the characteristics and treatment outcomes of ART cycles that were registered in
      2015. Methods: JSOG has requested all participating ART facilities to register
      cycle-specific information for all ART cycles since 2007. A descriptive analysis
      was performed by using the registry database for 2015. Results: In total, 424 151
      cycles and 51 001 neonates (1 in 19.7 neonates born in Japan) were registered in
      2015. The patients' mean age was 38.2 years (standard deviation = 4.5). Among the
      fresh cycles, 94 158 of 244 718 (38.5%) egg retrieval cycles were cycles with
      freeze-all embryos or oocytes, while fresh embryo transfer (ET) was performed in
      70 254 cycles, signaling a decrease from 2014. There were 169 898 frozen-thawed
      ET cycles, resulting in 56 355 pregnancies and 40 599 neonates. Single ET was
      performed at a rate of 79.7% for fresh and 81.8% for frozen cycles and the
      singleton pregnancy/live birth rates were 96.9%/96.5% and 96.8%/96.4% for the
      respective cycles. Conclusion: The total ART cycles and live births resulting
      from ART has been increasing in Japan. Single ET was performed at a rate of
      almost 80% and ET cycles have shifted from fresh to frozen cycles.

PMID- 29371816
TI  - Expression of the gonadotropin receptors during follicular development.
AB  - Background: Gonadotropins induce follicular development that leads to ovulation
      and luteinization. In women, the level of gonadotropins, along with the
      expression of their receptors, changes dynamically throughout the menstrual
      cycle. This study aimed to clarify the mechanisms underlying these phenomena.
      Methods: The literature was reviewed, including that published by the authors.
      Main findings Results: Follicle-stimulating hormone receptor expression in the
      granulosa cells was induced by androgens that were derived from growth
      differentiation factor-9-stimulated theca cells. In the theca cells, luteinizing
      hormone receptor (LHR) expression was noted from their appearance. In the
      granulosa cells, follicle-stimulating hormone (FSH) stimulation was essential for
      LHR expression. However, FSH alone was not sufficient to respond to the
      luteinizing hormone (LH) surge for oocyte maturation, ovulation, and subsequent
      luteinization. To achieve these stages, various local factors that were derived
      from the granulosa and theca cells in response to FSH and LH stimulation had to
      work synergistically in an autocrine/paracrine manner to strongly induce LHR
      expression. Following the LH surge, the LHR expression decreased markedly; miRNAs
      were involved in this transient LHR downregulation. Following ovulation, LHR
      expression drastically increased again toward luteinization. Conclusion: The
      expression of gonadotropin receptors is controlled by sophisticated and
      complicated systems; a breakdown of this system could lead to ovulation
      disorders.

PMID- 29371818
TI  - Measurement of endometrial thickness in premenopausal women in office gynecology.
AB  - Purpose: To define the median endometrial thickness (ET) in office gynecology is
      thought to be important for clinical practice. However, there are few reports
      about ET that have included the general female population on a large scale. The
      median ET was determined prospectively in premenopausal women who attended office
      gynecology for cervical cancer screening. Methods: In total, 849 women were
      enrolled. The median ET was determined by using transvaginal ultrasound and the
      relationships between the ET and various clinical factors were analyzed. Results:
      The participants' median age was 38.5 years. The median ET was 8.6 mm (90% and
      95% quantiles: 13.8 and 15.8 mm). The ET was not related to their age, symptoms,
      obstetric history, geographical location, or risk factors for endometrial cancer.
      In the women with a menstrual cycle length of 28-30 days, the ET was 7 mm on days
      1-6, but it increased from 5.4 mm immediately after menstruation (day 7 or 8) to
      9.2 mm on days 13-14. Subsequently, the ET increased further to 11.1 mm on day
      18. Conclusion: In all the women, the upper limit of the ET was 13.8 mm and 15.8
      mm in the 90% and 95% quantile, respectively, in office gynecology.

PMID- 29371819
TI  - Influence of multinerve-sparing, robot-assisted radical prostatectomy on the
      recovery of erection in Japanese patients.
AB  - Purpose: To evaluate in Japanese patients their sexual function after robot
      assisted radical prostatectomy (RARP) and to investigate the influence of the
      multinerve-sparing (NS) grade on their sexual function. Methods: In total, 225
      patients were reviewed with localized prostate cancer who underwent RARP at the
      authors' institution. They underwent RARP >3 months ago, without pre- and
      posthormone therapy and salvage radiation. Self-administered International Index
      of Erectile Function (IIEF) questionnaires were used for assessment
      preoperatively and 1-48 months postoperatively. In all, 129 patients were
      evaluated with the preoperative IIEF-Question 1 and who achieved a score of >=2
      by being divided into five NS groups. The recovery rates of erection
      (postoperative IIEF-Question 1 score of >=2) were calculated by using the Kaplan
      Meier analysis. Results: Seventy-four percent of all the patients had not
      attempted sexual intercourse, but 60% had felt sexual desire at 24 months
      postoperatively. In those patients with a preoperative erection, the recovery
      rate of erection was 58% at 24 months after the RARP. Across the five NS groups,
      as the procedure was more nerve-sparing, the recovery rate of erection became
      significantly higher. The postoperative effects on erection in the bilateral and
      unilateral NS groups were significantly superior to those in the other NS groups.
      Conclusion: In Japanese patients, erection after a RARP is improved with multiNS
      grade procedures.

PMID- 29371820
TI  - Nationwide survey of urological specialists regarding male infertility: results
      from a 2015 questionnaire in Japan.
AB  - Purpose: To investigate the incidence, etiology, treatment indications, and
      outcomes regarding infertile male patients in Japan. Methods: Between April, 2014
      and March, 2015, the authors contacted 47 clinical specialists in male
      infertility who had been certified by the Japan Society for Reproductive
      Medicine. The participating clinicians were sent a questionnaire regarding
      information on their infertile patients, according to etiology and the number and
      success rates of male infertility operations that had been performed in their
      practice. Results: Thirty-nine specialists returned the questionnaire and
      provided information regarding 7268 patients. The etiology of infertility
      included testicular factors, sexual disorders, and seminal tract obstruction.
      During the study year, the clinicians performed varicocelectomies, testicular
      sperm extractions (TESEs), and re-anastomoses of the seminal tract. The rate of
      successful varicocelectomies was >70%. The sperm retrieval rates with
      conventional TESE and microdissection TESE were 98.3% and 34.0%, respectively,
      while the patency rates with vasovasostomy and epididymovasostomy were 81.8% and
      61.0%, respectively. Conclusion: Surgical outcomes for infertile male patients
      are favorable and can be of great clinical benefit for infertile couples. To
      achieve this, urologists should work in collaboration with gynecological
      specialists in order to optimize the treatment of both partners.

PMID- 29371821
TI  - Single-dose pharmacokinetic study comparing the pharmacokinetics of recombinant
      human chorionic gonadotropin in healthy Japanese and Caucasian women and
      recombinant human chorionic gonadotropin and urinary human chorionic gonadotropin
      in healthy Japanese women.
AB  - Purpose: Recombinant hCG (r-hCG) was approved in Japan in 2016. As a prerequisite
      for a Phase III study in Japan related to this approval, the pharmacokinetic (PK)
      profile of r-hCG was investigated. Methods: An open-label, partly randomized,
      single-center, single-dose, group-comparison, Phase I PK-bridging study was done
      that compared a single 250 MUg dose of r-hCG with a single 5000 IU dose of
      urinary hCG (u-hCG) in healthy Japanese women, as well as comparing a single 250
      MUg dose of r-hCG in Japanese and Caucasian women. The Japanese participants were
      randomized 1:1 to receive either r-hCG or u-hCG, while the Caucasian participants
      were weight-matched to the Japanese participants who were receiving r-hCG in a
      1:1 fashion. The primary PK parameters were the area under the serum
      concentration-time curve from time 0 extrapolated to infinity (AUC 0-infinity)
      and the maximum serum concentration (Cmax). Results: The mean serum hCG
      concentration-time profiles of r-hCG in the Japanese and Caucasian participants
      were a similar shape, but the level of overall exposure was ~20% lower in the
      Japanese participants. For the Japanese participants, r-hCG resulted in an 11%
      lower Cmax but a 19% higher AUC 0-infinity compared with u-hCG. No new safety
      signal was identified. Conclusion: This study cannot exclude a potential
      difference in the PK profile of r-hCG between Japanese and Caucasian
      participants. However, this study does not indicate that there are clinically
      relevant differences in the serum PK of r-hCG and u-hCG in the Japanese
      participants.

PMID- 29371822
TI  - Superior clinical pregnancy rates after microsurgical epididymal sperm
      aspiration.
AB  - Purpose: To assess normal fertilization, clinical pregnancy, and live birth rates
      after the use of microscopic epididymal sperm aspiration (MESA). Methods: One
      hundred-and-sixty azoospermic participants who underwent MESA were evaluated. The
      MESA was performed by using a micropuncture method with a micropipette. In cases
      in which motile sperm were not obtained after the MESA, conventional or micro
      testicular sperm extraction (TESE) was completed. Results: Adequate motile sperm
      were retrieved in 71 participants by using MESA and in 59 out of 89 participants
      by using TESE. Of the total number of patients, 123 underwent intracytoplasmic
      sperm injection. After MESA, the normal fertilization rate was 73.5% and the
      clinical pregnancy rate per case was 95.7%. Healthy deliveries resulted after
      MESA in 65 (92.9%) cases and after TESE in 38 (71.7%) cases. Conclusion: The MESA
      specimen collection does not have any special requirements, such as mincing
      tissue disposition. The MESA also can reduce the amount of laboratory work that
      is needed for cryopreservation. In the authors' experience, MESA is a beneficial
      procedure and should be given priority over TESE.

PMID- 29371824
TI  - Characterization of oocyte retrieval cycles with empty zona pellucida.
AB  - Purpose: To identify the factors that characterize cycles with empty zona
      pellucida (EZP). Methods: Thirty-six oocyte retrieval cycles from which EZP were
      collected and another 36 cycles from which no EZP was collected were compared.
      The patients were divided into three groups: those with no EZP collected during
      any cycle, those with EZP collected during all cycles, and those experiencing
      cycles both with and without EZP. Results: The mean number of oocytes collected
      per cycle was higher in the cycles with EZP than without EZP. The fertilization
      rate of the collected oocytes and the rate of good embryo formation were
      significantly lower in the cycles with EZP. No significant difference was
      observed between the three groups in terms of age, number of oocytes collected,
      or hormone levels before and after the oocyte retrieval. The fertilization and
      pregnancy rates were highest in the patients with no EZP being collected during
      any cycle, followed by those experiencing cycles both with and without EZP, and
      then by those with EZP collected during all cycles. Conclusion: The observation
      of lower fertilization, poor embryo formation, and a low pregnancy rate in the
      patients with EZP suggests the poor quality of oocytes that were collected with
      EZP in the same cycle.

PMID- 29371823
TI  - Synchrony of the first division as an index of the blastocyst formation rate
      during embryonic development.
AB  - Purpose: To devise an uninvasive selection system for human embryos with high
      developmental potential after a single oocyte retrieval cycle by comparing the in
      vitro and in vivo effectiveness of first division synchrony against subsequent
      embryonic developmental stages. Methods: The effects of using assisted
      reproductive technology on 948 embryos that were produced in 137 cycles were
      examined by dividing the embryos into "early cleavage" (first division within
      25.90 hours) and "late cleavage" (first division at or after 25.90 hours) groups
      and comparing the blastocysts and good-quality blastocyst formation rates between
      the two groups. These two groups were each divided further into "high synchrony"
      (first division synchrony within 3.96 hours) and "low synchrony" (first division
      synchrony at or after 3.96 hours) groups. The blastocysts, good-quality
      blastocyst formation rates, and pregnancy rates were compared among these four
      groups. Results: Both the blastocysts and good-quality blastocyst formation rates
      were significantly higher in the early-cleavage groups than in the late-cleavage
      groups. The blastocyst formation rate of the latter was also significantly
      increased in the high-synchrony, compared with the low-synchrony, group.
      Conclusion: First division synchrony in a single oocyte retrieval cycle could be
      a useful assessment of the blastocyst formation rate that enables the selection
      of viable embryos at an early stage of culture.

PMID- 29371825
TI  - Retrospective cohort study of the risk factors for secondary infertility
      following hysteroscopic metroplasty of the uterine septum in women with recurrent
      pregnancy loss.
AB  - Purpose: A hysteroscopic metroplasty was performed for women with recurrent
      pregnancy loss owing to a uterine septum, following which some women became
      infertile. The aim of this study was to elucidate the risk factors of secondary
      infertility 1 year after hysteroscopic metroplasty for a uterine septum. Methods:
      A retrospective, single-center, cohort study included women with a history of at
      least two miscarriages that had been attributed to a uterine septum who underwent
      a hysteroscopic metroplasty. The patients' background data were compared between
      the patients who conceived and those who remained infertile at 1 year
      postoperatively. The data were analyzed by using the Mann-Whitney U-test and
      multivariate analyses. Results: The postoperative live birth rate was 83.9% (n =
      26), with persistent infertility in five women at 1 year. When comparing the
      pregnancy group with the infertile group, the women in the postoperative
      infertility group were significantly older than those in the postoperative
      pregnancy group. The multivariate analysis showed that age was an independent
      risk factor for persistent infertility. Conclusion: Age was identified as an
      independent risk factor for postoperative secondary infertility. Therefore,
      surgery as early as possible is recommended.

PMID- 29371828
TI  - Two cases of reversible male infertility due to congenital adrenal hyperplasia
      combined with testicular adrenal rest tumor.
AB  - Cases: Testicular adrenal rest tumor (TART) is one of the possible causes of male
      infertility, accompanied by congenital adrenal hyperplasia (CAH). Here are
      reported two cases of TARTs that were referred to Kobe City Medical Center West
      Hospital for the treatment of infertility and testicular tumors. Outcome: In one
      case, the semen analysis was improved from oligoasthenozoospermia to
      normozoospermia after taking oral glucocorticoid supplementation. The other case
      of original azoospermia showed that sperm had ejaculated into the semen after
      taking oral glucocorticoid supplementation. Conclusion: Although the prevalence
      of TARTs in male infertility is very rare, it is important to know how to
      approach this disease, considering the curable pathology of spermatogenesis and
      tumors resembling an appearance to germ cell tumors.

PMID- 29371827
TI  - Case of heterotopic cervical pregnancy and total placenta accreta after
      artificial cycle frozen-thawed embryo transfer.
AB  - Case: A 39-year-old woman presented with a genital hemorrhage at 5 weeks of
      gestation after an artificial cycle double frozen-thawed embryo transfer. She was
      diagnosed with a cervical heterotopic pregnancy. Although hormone supplementation
      was discontinued to terminate the pregnancy at 5 weeks of gestation, the
      intrauterine and cervical gestational sacs continued to develop. Outcome: The
      cervical gestational sac was surgically removed and the intrauterine pregnancy
      continued uneventfully, except for vasa previa. At 36 weeks of gestation, the
      patient underwent a cesarean section and gave birth to a healthy female infant.
      At the delivery, massive bleeding occurred and a hysterectomy was performed due
      to total placenta accreta. Conclusion: This case provides a novel example of a
      near-term delivery after a cervical heterotopic pregnancy and emphasizes the need
      for intensive care, even after the successful management of a cervical pregnancy.
      Most importantly, the present case implies a possible link between hormonal
      withdrawal and abnormal placentation.

PMID- 29371826
TI  - Long-term clinical outcomes of testicular sperm extraction and intracytoplasmic
      sperm injection for infertile men.
AB  - Purpose: To find the best methods to achieve the highest pregnancy and birth
      rates for couples needing testicular sperm extraction (TESE)-intracytoplasmic
      sperm injection (ICSI). Methods: Retrospectively studied were 801 patients with
      male factor infertility who had undergone TESE-ICSI between April, 1996 and July,
      2016 and who had been categorized into four groups: obstructive azoospermia (OA);
      non-obstructive azoospermia (NOA); Klinefelter syndrome (KS); and
      cryptozoospermia (Crypt). The sperm retrieval rate, hormone levels, fertilization
      rate (FR), pregnancy rate (PR), and birth rate (BR) after ICSI among three groups
      were compared: fresh testicular sperm (FS)-fresh oocytes (FO) (Group I); frozen
      thawed testicular sperm-FO (Group II); and FS-vitrified-warmed oocytes (Group
      III). Results: The testicular sperm recovery rate was 57.8% (463/801): 89.6% in
      the Crypt, 97.1% in the OA, 28.9% in the NOA, and 42.2% in the KS groups. The
      follicle-stimulating hormone levels were significantly higher in the NOA and KS
      groups and the testosterone levels were significantly lower in the KS group. The
      FR, PR, and BR were: 65.2%, 43.2%, and 28.5% in group I; 59.2%, 33.4%, and 18.7%
      in group II; and 56.4%, 33.8%, and 22.1% in group III. Conclusion:
      Intracytoplasmic sperm injection with FS-FO achieved the best PR and BR. It
      should be considered what to do in cases with no testicular sperm by TESE. The
      authors hope that ICSI with donor sperm will be allowed in Japan in the near
      future.

PMID- 29371829
TI  - Ultrasound-guided laparotomic oocyte retrieval during surgery for fertility
      preservation in a case of tumor recurrence after a unilateral salpingo
      oophorectomy.
AB  - Case: A 28 year old unmarried woman underwent a unilateral salpingo-oophorectomy
      and was suspected of having a malignant tumor in the remaining ovary. After
      consultation with the patient and her family, it was decided to cryopreserve the
      unfertilized oocytes. In order to reduce the risk of puncturing or rupturing the
      tumor when performing the oocyte retrieval from the ovary that was affected by
      the malignant tumor, it was chosen to use direct laparotomic oocyte retrieval
      during surgery, instead of conventional transvaginal retrieval. In order to
      further reduce the risk of tumor rupture, an ultrasound was used in the
      laparotomy field to precisely puncture only the follicle and thus avoid the
      tumor. A total of 11 oocytes was retrieved and 10 of them were cryopreserved in
      the MII phase. Outcome: By using an ultrasound at the same time as the oocyte
      retrieval, it was possible to avoid the ovarian tumor site. Furthermore, by
      checking and puncturing the follicles, it became possible to retrieve oocytes
      from the healthy parts of the ovary with greater precision. The combined use of
      an ultrasound with oocyte retrieval can be considered to be an effective method
      because it can be performed relatively easily. Conclusion: The authors believe
      that not only macroscopic, but also ultrasonic, methods are useful to reduce the
      risk of tumor rupture.

PMID- 29371830
TI  - A possible role for selenoprotein glutathione peroxidase (GPx1) and thioredoxin
      reductases (TrxR1) in thyroid cancer: our experience in thyroid surgery.
AB  - Background: Oxidative stress is responsible for some alterations in the chemical
      structure and, consequently, in the function of proteins, lipids, and DNA. Recent
      studies have linked oxidative stress to cancers, particularly thyroid cancer, but
      the mechanisms remain unclear. Here, we further characterize the role of
      oxidative stress in thyroid cancer by analyzing the expression of two selenium
      antioxidant molecules, glutathione peroxidase (GPx1) and thioredoxin reductase
      (TrxR1) in thyroid cancer cells. Methods: Samples of both healthy thyroid tissue
      and thyroid tumor were taken for analysis after total thyroidectomy. The
      expression of GPx1 and TrxR1 was revealed by Western blot analysis and quantified
      by densitometric analyses, while the evaluation of free radicals was performed by
      Electron Paramagnetic Resonance (EPR)-spin trapping technique. Results: Our
      results show a decrease in the expression of GPx1 and TrxR1 (- 45.7 and - 43.2%
      respectively, p < 0.01) in the thyroid cancer cells compared to the healthy
      cells. In addition, the EPR technique shows an increase of free radicals in tumor
      tissue, significantly higher than that found in healthy thyroid tissue (+ 116.3%,
      p < 0.01). Conclusions: Our findings underscore the relationship between thyroid
      cancer and oxidative stress, showing the imbalance of the oxidant/antioxidant
      system in thyroid cancer tissue. These results suggest that either the inability
      to produce adequate antioxidant defense or an increased consumption of
      antioxidants, due to the hyper-production of free radicals, may play a crucial
      role in thyroid cancer.

PMID- 29371831
TI  - SHP-2 restricts apoptosis induced by chemotherapeutic agents via Parkin-dependent
      autophagy in cervical cancer.
AB  - Background: Autophagy is a cell degradation pathway that eliminates damaged or
      unwanted proteins and organelles. Autophagy protects cells from chemotherapeutic
      agents by scavenging damaged mitochondria. Methods: Plasmid transfection and
      shRNA were used to regulate SHP-2 expression. Annexin V/PI staining were employed
      to analysis apoptosis. Flow cytometry was used to analyse intracellular calcium
      level and ROS. Immunofluorescence was used to detect mitochondria membrane
      potential, autophagy and Parkin translocation. Results: In cervical cancer, we
      found that SHP-2 suppressed apoptosis induced by Oxaliplatin and 5-FU. Further
      studies have found that SHP-2 protects against mitochondrial damage. This role of
      SHP-2 is associated with the activation of autophagy. In addition, SHP-2 degraded
      impaired mitochondria dependent on the ubiquitin ligase function of Parkin.
      Conclusions: These results suggest that SHP-2 inhibits the apoptosis induced by
      chemotherapeutic drugs through activating autophagy to degrade damaged
      mitochondria and ubiquitin ligase Parkin involved in SHP-2 induced autophagy.

PMID- 29371832
TI  - Xenogeneic cell therapy provides a novel potential therapeutic option for cancers
      by restoring tissue function, repairing cancer wound and reviving anti-tumor
      immune responses.
AB  - Conventional cancer treatments such as surgery, radiotherapy, chemotherapy and
      targeted therapy, not only destruct tumors, but also injure the normal tissues,
      resulting in limited efficacy. Recent advances in cancer therapy have aimed at
      changing the host milieu of cancer against its development and progression by
      targeting tumor microenvironment and host immune system to eradicate tumors. To
      the host body, tumors arise in tissues. They impair the normal healthy tissue
      physiological function, become chronically inflamed and develop non-healing or
      overhealing wounds as well as drive immuno-suppressive activity to escape
      immunity attack. Therefore, the rational therapeutic strategies for cancers
      should treat both the tumors and the host body for the best efficacy to turn the
      deadly malignant disease to a manageable one. Xenogeneic cell therapy (i.e.
      cellular xenotransplantation) using cells from non-human source animals such as
      pigs has shown promising results in animal studies and clinical
      xenotransplantation in restoring lost tissue physiological function and repairing
      the wound. However, the major hurdle of xenogeneic cell therapy is the host
      immunological barriers that are induced by transplanted xenogeneic cells to
      reject xenografts. Possibly, the immunological barriers of xenogeneic cells could
      be used as immunological boosters to activate the host immune system. Here, we
      hypothesized that because of the biological properties of xenogeneic cells to the
      recipient humans, the transplantation of xenogeneic cells (i.e. cellular
      xenotransplantation) into cancer patients' organs of the same origin with
      developed tumors may restore the impaired function of organs, repair the wound,
      reduce chronic inflammation and revive the anti-tumor immunity to achieve
      beneficial outcome for patients.

PMID- 29371833
TI  - Effects of prescription restrictive interventions on antibiotic procurement in
      primary care settings: a controlled interrupted time series study in China.
AB  - Background: The overuse of antibiotics has been identified as a major challenge
      in regard to the rational prescription of medicines in low and middle income
      countries. Extensive studies on the effectiveness of persuasive interventions,
      such as guidelines have been undertaken. There is a dearth of research pertaining
      to the effects of restrictive interventions. This study aimed to evaluate the
      impacts of prescription restrictions in relation to types and administration
      routes of antibiotics on antibiotic procurement in primary care settings in
      China. Methods: Data were drawn from the monthly procurement records of medicines
      for primary care institutions in Hubei province over a 31-month period from May
      2011 to November 2013. We analyzed the monthly procurement volume and costs of
      antibiotics. Interrupted time series analyses with a difference-in-difference
      approach were performed to evaluate the effect of the restrictive intervention
      (started in August 2012) on antibiotic procurement in comparison with those for
      cardiovascular conditions. Sensitivity tests were performed by replacing outliers
      using a simple linear interpolation technique. Results: Over the entire study
      period, antibiotics accounted for 33.65% of the total costs of medicines procured
      for primary care institutions: mostly non-restricted antibiotics (86.03%) and
      antibiotics administered through parenteral routes (79.59%). On average, 17.14
      million defined daily doses (DDDs) of antibiotics were procured per month, with
      the majority (93.09%) for non-restricted antibiotics and over half (52.38%) for
      parenteral administered antibiotics. The restrictive intervention was associated
      with a decline in the secular trend of costs for non-restricted oral antibiotics
      (- 0.36 million Yuan per month, p = 0.029), and for parenteral administered
      restricted antibiotics (- 0.28 million Yuan per month, p = 0.019), as well as a
      decline in the secular trend of procurement volume for parenteral administered
      non-restricted antibiotics (- 0.038 million DDDs per month, p = 0.05).
      Conclusions: Restrictive interventions are effective in reducing the procurement
      of antibiotics. However, the effect size is relatively small and antibiotic
      consumptions remain high, especially parenteral administered antibiotics.

PMID- 29371834
TI  - An Interactive Simulation Program for Exploring Computational Models of Auto
      Associative Memory.
AB  - While neuroscience students typically learn about activity-dependent plasticity
      early in their education, they often struggle to conceptually connect
      modification at the synaptic scale with network-level neuronal dynamics, not to
      mention with their own everyday experience of recalling a memory. We have
      developed an interactive simulation program (based on the Hopfield model of auto
      associative memory) that enables the user to visualize the connections generated
      by any pattern of neural activity, as well as to simulate the network dynamics
      resulting from such connectivity. An accompanying set of student exercises
      introduces the concepts of pattern completion, pattern separation, and sparse
      versus distributed neural representations. Results from a conceptual assessment
      administered before and after students worked through these exercises indicate
      that the simulation program is a useful pedagogical tool for illustrating
      fundamental concepts of computational models of memory.

PMID- 29371835
TI  - Diversity of Graduates from Bachelor's, Master's and Doctoral Degree Neuroscience
      Programs in the United States.
AB  - The demography of United States graduates from science, technology, engineering,
      and math (STEM) degree programs is well-understood; however, data particularly
      describing the gender and ethnic diversity of graduates of neuroscience programs
      has not been analyzed, limiting our knowledge of specific areas where diversity
      and fair representation are lacking. Using over 30 years of data from the
      National Center for Education Statistics, we documented the demography of
      neuroscience graduates from bachelor's, master's, and doctoral degree programs.
      Recent graduation trends indicate greater numbers of female graduates from
      bachelor's and graduate degree programs. White (non-Hispanic) males and females
      represent the largest group of graduates while Asian/Pacific Islanders represent
      the largest non-White group of graduates. Although the number of underrepresented
      minorities graduating from neuroscience degree programs at every level has
      increased in recent years, they still lag compared to White (non-Hispanic) and
      Asian/Pacific Islanders. These data provide valuable information that can be used
      to promote greater diversity among neuroscience graduates by higher education
      faculty and administrators and federal funding agencies.

PMID- 29371836
TI  - A Case Study in the Use of Primary Literature in the Context of Authentic
      Learning Pedagogy in the Undergraduate Neuroscience Classroom.
AB  - Providing opportunities for undergraduate science students to develop causal
      reasoning skills and the ability to think like research scientists is a crucial
      part of their preparation for professional practice as a scientist and/or a
      clinician. This has led many to question whether the traditional academic in
      class lecture still has a functional role in today's undergraduate science
      education. Here, we performed a case study to attempt to maximize the use of in
      class time to create a more authentic learning opportunity for undergraduate
      neuroscience students in our institution, the majority of whom go on to be
      research active scientists. We hypothesised that using seminal research papers as
      a teaching tool in a flipped classroom setting would model for neuroscience
      students what it means to think like a research scientist, would provide an
      opportunity for them to develop their causal reasoning skills and allow them to
      become more comfortable with the nature of professional practice (i.e., research)
      in the context of the discipline. We describe the design and implementation of
      this teaching approach to undergraduate final year neuroscience students, and
      evaluate their perception of it. We provide evidence that this approach models
      for the students what it means to reason like a research scientist, and discuss
      the implications of these findings for future practice. We propose that these
      findings will help add to the educational experience of all Neuroscience students
      whether they are on pre-med or on a research track.

PMID- 29371837
TI  - Measuring Salivary Alpha-Amylase in the Undergraduate Neuroscience Laboratory.
AB  - Undergraduate courses in biopsychology, neuroscience, and physiology often
      include laboratory exercises that examine responses to stimulation of the
      sympathetic nervous system with measurements of heart rate, blood pressure, or
      galvanic skin levels (sweat response). A newer bioindicator of the sympathetic
      nervous system is salivary alpha-amylase (sAA) measured with a colorimetic enzyme
      assay. Undergraduate students successfully measured a rise in sAA due to the
      stress of giving a class presentation (n=13). Students were enthusiastic to
      measure a physiological response to a real-life anxiety-producing situation. We
      describe potential difficulties in the assay and our adaptations to the
      manufacturer's protocol to make it more feasible in the undergraduate setting.

PMID- 29371838
TI  - An Attitudinal Survey of Undergraduate Neuroscience Students Regarding Their
      Views on the Relevance of Lectures to their Education.
AB  - Advances in technology have seen a significant growth in the integration of e
      learning into university education. Coupled with this trend are the learning
      approaches used by "Generation Connected" or GenC students, whose prolific use of
      digital technology is a defining characteristic. This has resulted in questions
      being asked as to whether in-class university lecture time is still relevant to
      university education. Here we conducted a case study with a group of
      undergraduate neuroscience students to assess their views on the relevance of
      attending lectures, why they attend or the reasons for non-attendance, and on
      what makes a good lecture. This is with a view to informing the design of new
      teaching approaches that may be more beneficial in maximising student engagement,
      and facilitating learning. The survey instrument was a ten-item questionnaire
      that collected both qualitative and quantitative data. Over 90% of students were
      of the view that lectures were beneficial to their learning, while only 4%
      thought they were an outdated mode of education. Three main themes emerged when
      students were asked what makes a good lecture: 1. Engagement, 2. Time, and 3.
      Varied format. We discuss the implications of these findings and suggest how
      these student views could be woven into the design of teaching approaches to
      increase the relevance of in-class lecture time in undergraduate neuroscience
      education.

PMID- 29371840
TI  - Cartoon Network: A tool for open-ended exploration of neural circuits.
AB  - Cartoon Network is an open-source simulator for neural circuits. It was designed
      to provide a microworld for the playful exploration of neural networks (similar
      to the niche Logo/Scratch fills for computer programming). The simulator makes it
      easy to construct and experiment with closed-loop circuits, enabling students to
      explore how small sets of neurons can generate complex patterns of activity
      (oscillations, reverberation). Cartoon Network can be connected to the Finch
      robot from BirdBrain Technologies, a cheap USB robotics platform. This enables
      students to design a nervous system for a Finch, creating sensory neurons which
      read Finch inputs (touch, light, and temperature), motor neurons which control
      Finch outputs (wheels, lights, and sound), and interneurons to produce intrinsic
      activity and/or link together inputs and outputs in ways that can produce complex
      and surprising behaviors. Students use Cartoon Network by taking on structured
      challenges (For example, can you make the Finch follow a light? Can it turn and
      run when it bumps a wall?) that require deep engagement with important principles
      of neural circuit operation (e.g., lateral inhibition, parallel processing,
      positive- and negative-feedback). On successfully completing a challenge,
      students can systematically explore the neural properties that help control the
      behavior, compare their work to other successful designs, and/or reflect on how
      the circuit they designed might be modified via evolution to produce different
      behaviors. Cartoon Network has proven an engaging and effective activity for
      undergraduates and is accessible for students as young as late elementary school.
      Download it for free at: https://github.com/rcalinjageman/cartoon_network.

PMID- 29371839
TI  - Using the Tools of Behavioral Neuroscience to Determine the Identity of Different
      Mouse Strains in a Laboratory Course.
AB  - Understanding the neural mechanisms underlying behavior depends on our ability to
      define and to measure these behaviors in the model animal. We describe an upper
      level course which provides students with hands-on experience in the methods of
      behavioral neuroscience. There are many well-established behavioral tests which
      are relatively easy for students to conduct that can be used to determine the
      performance of animals in such tasks as anxiety, motor performance and memory.
      Laboratory mice bred specifically to exhibit particular behavioral
      characteristics are readily available from vendors along with well documented
      behavioral profiles for these strains. We used two albino strains CD1 and BALBc
      as our model animals. Students were given the task of identifying the strains
      based on the results of a battery of behavioral tests but were not given
      information about the mice. These two strains were chosen for their clear
      differences particularly in tests of anxiety. Students conducted elevated plus
      maze and zero maze tests, open field test, light-dark exploratory task, rotarod,
      balance beam test, spatial or novel object learning. Students were able to
      correctly identify the two strains by comparing their own data with the published
      literature in the field. The course structure encouraged students to work in
      teams to design protocols, and then to collect and explore data. Students were
      enthusiastic about the hands-on laboratory experience and were able to
      demonstrate an appreciation for and understanding of these methods in behavioral
      neuroscience.

PMID- 29371841
TI  - "Brevity is the Soul of Wit": Use of a Stepwise Project to Teach Concise
      Scientific Writing.
AB  - Skillful writing is essential for professionals in science and medicine.
      Consequently, many undergraduate institutions have adjusted their curriculum to
      include in-depth instruction and practice in writing for students majoring in the
      sciences. In neuroscience, students are often asked to write a laboratory report
      in the style of a primary scientific article or a term paper structured like a
      review article. Typically, students write section by section and build up to the
      final draft of a complete paper. In this way, students learn how to write a
      scientific paper. While learning to write such a paper is important, this is not
      the only type of written communication relevant to scientific careers. Here, I
      describe a stepwise writing project aimed to improve editing, succinctness, and
      the ability to synthesize the literature. Furthermore, I provide feedback from
      the students, and discuss the advantages and challenges of this project.

PMID- 29371842
TI  - Using Action-Mapping to Design a Non-Majors Neuroeconomics Course to Teach First
      Year Collegiate Skills.
AB  - With its ability to address questions about how decisions are made and why,
      neuroeconomics is an excellent topic of study for college students at a variety
      of levels. In this paper we detail a neuroeconomics course specifically modified
      for undecided First-year students. One particularly daunting challenge was
      defining clear outcomes and delivering instruction at an appropriate level. We
      used Action-Mapping to achieve the course objectives of teaching collegiate
      skills applicable to any path of study or career while also delivering content
      suitable for credits in both a social science and natural science.

PMID- 29371843
TI  - Characterizing the Undergraduate Neuroscience Major in the U.S.: An Examination
      of Course Requirements and Institution-Program Associations.
AB  - Neuroscience is a rapidly expanding field, and many colleges and universities
      throughout the country are implementing new neuroscience degree programs. Despite
      the field's growth and popularity, little data exists on the structural character
      of current undergraduate neuroscience programs. We collected and examined
      comprehensive data on existing undergraduate neuroscience programs, including
      academic major requirements and institution characteristics such as size,
      financial resources, and research opportunities. Thirty-one variables covering
      information about course requirements, department characteristics, financial
      resources, and institution characteristics were collected from 118 colleges and
      universities in the United States that offer a major titled "neuroscience" or
      "neural sciences." Data was collected from publicly available sources (online
      databases, institutions' neuroscience program websites) and then analyzed to
      define the average curriculum and identify associations between institution and
      program characteristics. Our results suggest that the average undergraduate
      neuroscience major requires 3 chemistry, 3 biology, 3 laboratory, 2-3
      neuroscience, 1 physics, 1 math, and 2 psychology courses, suggesting that most
      neuroscience programs emphasize the natural sciences over the social sciences.
      Additionally, while 98% of institutions in our database offer research
      opportunities, only 31% required majors to perform research. Of note, 70% of
      institutions offering a neuroscience major do not have a neuroscience department,
      suggesting that most institutions offer neuroscience as an interdisciplinary
      major spanning several departments. Finally, smaller liberal arts colleges
      account for the majority of institutions offering a neuroscience major. Overall,
      these findings may be useful for informing groups interested in undergraduate
      neuroscience training, including institutions looking to improve or establish
      programs, students wanting to major in neuroscience and employers hiring
      neuroscience graduates.

PMID- 29371844
TI  - Teaching with Big Data: Report from the 2016 Society for Neuroscience Teaching
      Workshop.
AB  - As part of a series of workshops on teaching neuroscience at the Society for
      Neuroscience annual meetings, William Grisham and Richard Olivo organized the
      2016 workshop on "Teaching Neuroscience with Big Data." This article presents a
      summary of that workshop. Speakers provided overviews of open datasets that could
      be used in teaching undergraduate courses. These included resources that already
      appear in educational settings, including the Allen Brain Atlas (presented by
      Joshua Brumberg and Terri Gilbert), and the Mouse Brain Library and GeneNetwork
      (presented by Robert Williams). Other resources, such as NeuroData (presented by
      William R. Gray Roncal), and OpenFMRI, NeuroVault, and Neurosynth (presented by
      Russell Poldrack) have not been broadly utilized by the neuroscience education
      community but offer obvious potential. Finally, William Grisham discussed the
      iNeuro Project, an NSF-sponsored effort to develop the necessary curriculum for
      preparing students to handle Big Data. Linda Lanyon further elaborated on the
      current state and challenges in educating students to deal with Big Data and
      described some training resources provided by the International Neuroinformatics
      Coordinating Facility. Neuroinformatics is a subfield of neuroscience that deals
      with data utilizing analytical tools and computational models. The feasibility of
      offering neuroinformatics programs at primarily undergraduate institutions was
      also discussed.

PMID- 29371845
TI  - Integrating Brain Science into Health Studies: An Interdisciplinary Course in
      Contemplative Neuroscience and Yoga.
AB  - As neuroscience knowledge grows in its scope of societal applications so does the
      need to educate a wider audience on how to critically evaluate its research
      findings. Efforts at finding teaching approaches that are interdisciplinary,
      accessible and highly applicable to student experience are thus ongoing. The
      article describes an interdisciplinary undergraduate health course that combines
      the academic study of contemplative neuroscience with contemplative practice,
      specifically yoga. The class aims to reach a diverse mix of students by teaching
      applicable, health-relevant neuroscience material while directly connecting it to
      first-hand experience. Outcomes indicate success on these goals: The course
      attracted a wide range of students, including nearly 50% non-science majors. On a
      pre/post test, students showed large increases in their knowledge of
      neuroscience. Students' ratings of the course overall, of increases in positive
      feelings about its field, and of their progress on specific course objectives
      were highly positive. Finally, students in their written work applied
      neuroscience course content to their personal and professional lives. Such
      results indicate that this approach could serve as a model for the
      interdisciplinary, accessible and applied integration of relevant neuroscience
      material into the undergraduate health curriculum.

PMID- 29371846
TI  - Learning Experimental Design through Targeted Student-Centric Journal Club with
      Screencasting.
AB  - Knowledge and application of experimental design principles are essential
      components of scientific methodology, and experience with these skills is
      fundamental for participating in scientific research. However, undergraduates
      often enter the research laboratory with little training in designing and
      interpreting their own experiments. In the context of a research university
      laboratory, we designed a journal club training exercise to address this need.
      Students were instructed on methods for interpreting scientific literature using
      a screencast, a digital recording of a slide presentation narrated by an
      instructor. Students subsequently examined a series of research publications with
      a focus on the experimental designs and data interpretation in a two-session
      group discussion journal club format. We have found this approach to be an
      efficient and productive method for engaging students in learning about
      principles of experimental design and further preparing them for success in
      laboratory research.

PMID- 29371847
TI  - Interviewing Neuroscientists for an Undergraduate Honors Project.
AB  - Honors projects that supplement standard coursework are a widely used practice in
      undergraduate curricula. These projects can take many forms, ranging from
      laboratory research projects to performing service learning to literature
      analyses. Here we discuss an honors project focused on interviewing
      neuroscientists to learn about individual scientific practice and career paths,
      and synthesizing the resulting information into a personal reflection essay. We
      detail step-by-step instructions for performing this type of project, including
      how to develop interview questions, a sample project timeline, deliverables,
      learning objectives and outcomes, and address potential pitfalls. We provide
      sample interview questions, an interview solicitation email, and in the
      supplemental materials an example student reflection essay, assessment rubrics,
      and the transcription of a student-conducted interview of Drs. John Godwin and
      Santosh Mishra of North Carolina State University. This type of project is a
      promising method to enable student-researcher communication, and potentially
      useful to a broad spectrum of both honors and non-honors neuroscience coursework.

PMID- 29371848
TI  - Front and Back Flipping for Neurobiology! Developing a Hybrid Upper-Division Lab
      Course.
AB  - Flipped instruction using online enrichment is a popular way to enhance active
      learning in the laboratory setting. Graduate student teaching assistants at
      University of California, Irvine flipped an upper division undergraduate
      neurobiology and behavior lab using the new online software platform "Rocketmix."
      The following research study compares the impact of pre-lab online instruction
      (front flipping) and post-lab online instruction (back flipping) on student exam
      performance. We describe a novel method for unbiased categorization of exam
      questions by degree of difficulty. Multi-choice instruction encourages students
      to consider all distractors and discourages verbal cues and process of
      elimination techniques. Eighteen identical questions were evenly distributed
      across exam versions with multiple choice instruction (single answer) or a more
      challenging multi-choice instruction (more than one answer). Student performance
      on multiple choice questions were used to categorize the degree of difficulty of
      questions that were presented in multi-choice format. Our findings reveal that
      pre-lab instruction resulted in better student performance compared with post-lab
      instruction on questions of moderate difficulty. This effect was significant for
      both male and female students. Student survey data on the flipped lab format is
      provided, indicating that students appreciated the online instructional modules,
      finding them both informative and useful during lab exercises and exams.

PMID- 29371849
TI  - An Integrative Approach to STEM Concepts in an Introductory Neuroscience Course:
      Gains in Interdisciplinary Awareness.
AB  - Neuroscience is an integrative discipline for which students must achieve broad
      based proficiency in many of the sciences. We are motivated by the premise that
      student pursuit of proficiency in science, technology, engineering, and
      mathematics (STEM) can be supported by awareness of the application of knowledge
      and tools from the various disciplines for solving complex problems. We refer to
      this awareness as "interdisciplinary awareness." Faculty from biology, chemistry,
      mathematics/computer science, physics, and psychology departments contributed to
      a novel integrative introductory neuroscience course with no pre-requisites. STEM
      concepts were taught in "flipped" class modules throughout the semester: Students
      viewed brief videos and completed accompanying homework assignments
      independently. In subsequent class meetings, students applied the STEM concepts
      to understand nervous system structure and function through engaged learning
      activities. The integrative introduction to neuroscience course was compared to
      two other courses to test the hypothesis that it would lead to greater gains in
      interdisciplinary awareness than courses that overlap in content but were not
      designed for this specific goal. Data on interdisciplinary awareness were
      collected using previously published tools at the beginning and end of each
      course, enabling within-subject analyses. Students in the integrative course
      significantly increased their identification of scientific terms as relevant to
      neuroscience in a term-discipline relevance survey and increased their use of
      terms related to levels of analysis (e.g., molecular, cellular, systems) in
      response to an open-ended prompt. These gains were seen over time within the
      integrative introduction to neuroscience course as well as relative to the other
      two courses.

PMID- 29371851
TI  - After p Values: The New Statistics for Undergraduate Neuroscience Education.
AB  - Statistical inference is a methodological cornerstone for neuroscience education.
      For many years this has meant inculcating neuroscience majors into null
      hypothesis significance testing with p values. There is increasing concern,
      however, about the pervasive misuse of p values. It is time to start planning
      statistics curricula for neuroscience majors that replaces or de-emphasizes p
      values. One promising alternative approach is what Cumming has dubbed the "New
      Statistics", an approach that emphasizes effect sizes, confidence intervals, meta
      analysis, and open science. I give an example of the New Statistics in action and
      describe some of the key benefits of adopting this approach in neuroscience
      education.

PMID- 29371850
TI  - Using Case Studies to Promote Student Engagement in Primary Literature Data
      Analysis and Evaluation.
AB  - Analyzing and evaluating primary literature data is a common learning objective
      in undergraduate neuroscience courses. However, students with more clinically
      focused career goals often dismiss the relevance of evaluating basic neuroscience
      literature. Here, we describe using case studies to promote student engagement in
      primary literature in a cellular and molecular neuroscience course. Two example
      literature-based case studies are provided: Untwisting Pretzel Syndrome, a
      neurodevelopment case exploring synapse formation in a pretzel syndrome patient,
      and The Trials of ALS, a neurodegeneration case exploring axon degeneration and
      repair in an amyotrophic lateral sclerosis patient. These cases were assigned
      after neurodevelopment and neurodegeneration lectures covering key concepts. Both
      cases begin by introducing the patient and hypothesizing symptoms and diagnoses,
      followed by scenes incorporating primary data to illustrate disease pathogenesis
      and treatments. Students complete questions embedded in these cases as homework,
      and class time is used to discuss their answers. Discussion emphasizes that there
      can be multiple "correct" answers, and the best answers are accurate and well
      supported. Accordingly, students edit their answers in class, and these
      annotations are factored into a pass/fail grade on the case. Additional scenes
      and questions from the same case studies are used on the course's take-home
      exams, thereby allowing students to practice primary data analysis and evaluation
      before a graded assignment. Student evaluations support literature-based case
      studies as an effective learning tool, with students identifying cases as the
      most valuable aspect of the course, and reporting increased confidence in
      understanding cellular and molecular neuroscience.

PMID- 29371852
TI  - Devising a Method to Study if Wernicke's Aphasia Patients are Aware That They Do
      Not Comprehend Language or Speak It Understandably.
AB  - Wernicke's Aphasia (WA) is characterized by an individual speaking fluent
      gibberish without the ability to understand anything that is said to them or
      anything they attempt to read. It is caused by damage to the left posterior
      temporoparietal cortex, also known as Wernicke's area. An additional intriguing
      symptom of WA patients is their apparent obliviousness to their own lack of
      understanding despite their intact reasoning or other cognitive abilities. Their
      only deficit seems to be in the basic rules of language that define word meaning,
      also known as phonology. Growing out of a project in an undergraduate class, we
      devised a phonology-free approach to communicating with WA patients that attempts
      to answer the questions of whether WA patients know that they do not understand
      what is said to them, that others do not understand what they have said, and if
      these patients are distressed by this lack of communication. We here describe the
      process and the resulting method.

PMID- 29371853
TI  - The University of Ibadan/Grass Foundation Workshop in Neuroscience Teaching.
AB  - The University of Ibadan/Grass Foundation Workshop in Neuroscience Teaching
      (March 31st to April 2nd, 2017) in Ibadan, Nigeria was sponsored by the Grass
      Foundation as a "proof of principle" outreach program for young neuroscience
      faculty at Nigerian universities with limited educational and research resources.
      The workshop's goal was to introduce low cost equipment for student lab exercises
      and computational tutorials that could enhance the teaching and research
      capabilities of local neuroscience educators. Participant assessment of the
      workshop's activities was very positive and suggested that similar workshops for
      other faculty from institutions with limited resources could have a great impact
      on the quality of both the undergraduate and faculty experience.

PMID- 29371854
TI  - For the FUN of It.

PMID- 29371855
TI  - A Guerilla Guide to Common Problems in 'Neurostatistics': Essential Statistical
      Topics in Neuroscience.
AB  - Effective inferential statistical analysis is essential for high quality studies
      in neuroscience. However, recently, neuroscience has been criticised for the poor
      use of experimental design and statistical analysis. Many of the statistical
      issues confronting neuroscience are similar to other areas of biology; however,
      there are some that occur more regularly in neuroscience studies. This review
      attempts to provide a succinct overview of some of the major issues that arise
      commonly in the analyses of neuroscience data. These include: the non-normal
      distribution of the data; inequality of variance between groups; extensive
      correlation in data for repeated measurements across time or space; excessive
      multiple testing; inadequate statistical power due to small sample sizes; pseudo
      replication; and an over-emphasis on binary conclusions about statistical
      significance as opposed to effect sizes. Statistical analysis should be viewed as
      just another neuroscience tool, which is critical to the final outcome of the
      study. Therefore, it needs to be done well and it is a good idea to be proactive
      and seek help early, preferably before the study even begins.

PMID- 29371856
TI  - Three Scientific Controversies to Engage Students in Reading Primary Literature.
AB  - In this review, three sets of papers are presented. Each of the sets presents a
      historical or active controversy in neuroscience ranging from cell biology and
      cell signaling, to developmental neuroscience, to cognitive neuroscience. The
      first set captures a historical controversy about whether the beta/gamma subunit
      of G-proteins can be active in opening ion channels. The second set represents a
      modern instantiation of the oldest debate in neuroscience: are our minds and
      brains the product of innate factors or environmental influences. This debate
      plays out in a series of papers on the development of the visual system. The
      third set contrasts the view that the hippocampus and surrounding structures
      primarily function to represent our location in space (a position for which the
      2014 Nobel Prize in Physiology or Medicine was awarded to three investigators)
      with the perspective that the hippocampus is a general-purpose structure for
      declarative memories, spatial or non-spatial. The first and third controversies
      feature publications of virtually identical experiments that show opposing
      results. All three controversies are discussed in regards to the individual
      scientists who did the experiments and debated directly with each other. The
      first (beta/gamma subunits) emphasizes the value of reproducibility in scientific
      research, the second (visual cortex development) emphasizes the value of new
      techniques and updating scientific models, and the third (hippocampus) exposes
      students to an ongoing, albeit under discussed, debate.

PMID- 29371857
TI  - Nutritional strategies of high level natural bodybuilders during competition
      preparation.
AB  - Background: Competitive bodybuilders employ a combination of resistance training,
      cardiovascular exercise, calorie reduction, supplementation regimes and peaking
      strategies in order to lose fat mass and maintain fat free mass. Although
      recommendations exist for contest preparation, applied research is limited and
      data on the contest preparation regimes of bodybuilders are restricted to case
      studies or small cohorts. Moreover, the influence of different nutritional
      strategies on competitive outcome is unknown. Methods: Fifty-one competitors (35
      male and 16 female) volunteered to take part in this project. The British Natural
      Bodybuilding Federation (BNBF) runs an annual national competition for high level
      bodybuilders; competitors must qualify by winning at a qualifying events or may
      be invited at the judge's discretion. Competitors are subject to stringent drug
      testing and have to undergo a polygraph test. Study of this cohort provides an
      opportunity to examine the dietary practices of high level natural bodybuilders.
      We report the results of a cross-sectional study of bodybuilders competing at the
      BNBF finals. Volunteers completed a 34-item questionnaire assessing diet at three
      time points. At each time point participants recorded food intake over a 24-h
      period in grams and/or portions. Competitors were categorised according to
      contest placing. A "placed" competitor finished in the top 5, and a "Non-placed"
      (DNP) competitor finished outside the top 5. Nutrient analysis was performed
      using Nutritics software. Repeated measures ANOVA and effect sizes (Cohen's d)
      were used to test if nutrient intake changed over time and if placing was
      associated with intake. Results: Mean preparation time for a competitor was 22 +/
      9 weeks. Nutrient intake of bodybuilders reflected a high-protein, high
      carbohydrate, low-fat diet. Total carbohydrate, protein and fat intakes decreased
      over time in both male and female cohorts (P < 0.05). Placed male competitors had
      a greater carbohydrate intake at the start of contest preparation (5.1 vs 3.7
      g/kg BW) than DNP competitors (d = 1.02, 95% CI [0.22, 1.80]). Conclusions:
      Greater carbohydrate intake in the placed competitors could theoretically have
      contributed towards greater maintenance of muscle mass during competition
      preparation compared to DNP competitors. These findings require corroboration,
      but will likely be of interest to bodybuilders and coaches.

PMID- 29371858
TI  - Bioinformatics-based identification of miR-542-5p as a predictive biomarker in
      breast cancer therapy.
AB  - Background: Tamoxifen is the first-line hormone therapy for estrogen receptor
      alpha positive (ERalpha+) breast cancer. However, about 40% of patients with
      ERalpha + breast cancer who receive tamoxifen therapy eventually develop
      resistance resulting in a poor prognosis. The aim of this study was to mine
      available data sets in the Gene Expression Omnibus (GEO) database, including in
      vitro (cell lines) and in vivo (tissue samples), and to identify all miRNAs
      associated with tamoxifen resistance (TamR) in breast cancer. Secondly, this
      study aimed to predict the key gene regulatory networks of newly found TamR
      related miRNAs and evaluate the potential role of the miRNAs and targets as
      potential prognosis biomarkers for breast cancer patients. Result: Microarray
      data sets from two different studies were used from the GEO database: 1.
      GSE66607: miRNA of MCF-7 TamR cells; 2. GSE37405: TamR tissues. Differentially
      expressed microRNAs (miRNAs) were identified in both data sets and 5
      differentially expressed miRNAs were found to overlap between the two data sets.
      Profiles of GSE37405 and data from the Kaplan-Meier Plotter Database (KMPD) along
      with Gene Expression Profiling Interactive Analysis (GEPIA) were used to reveal
      the relationship between these 5 miRNAs and overall survival. The results showed
      that has-miR-542-5p was the only miRNA associated with overall survival of
      ERalpha + breast cancer patients who received adjuvant tamoxifen. Targets of has
      miR-542-5p were predicted by miRanda and TargetScan, and the mRNA expression of
      the three 3 target gene, Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase
      Activation Protein Beta (YWHAB), Lymphocyte Antigen 9 (LY9), and Secreted
      Frizzled Related Protein 1 (SFRP1) were associated with overall survival in 2
      different databases. Copy-number alterations (CNAs) of SFRP1 confer survival
      disadvantage to breast cancer patients and alter the mRNA expression of SFRP1 in
      cBioPortal database. Conclusion: This study indicates that miRNA has-miR-542-5p
      is associated with TamR and can predict prognosis of breast cancer patients.
      Furthermore, has-miR-542-5p may be acting through a mechanism involving the
      target genes YWHAB, LY9, and SFRP1. Overall, has-miR-542-5p is a predictive
      biomarker and potential target for therapy of breast cancer patients.

PMID- 29371859
TI  - Young adults report increased pleasure from smoking cigarettes when drinking
      alcohol but not when using marijuana.
AB  - Background: Among young adults, cigarette smoking is strongly associated with
      alcohol and marijuana use. The present study compared self-reported co-use of
      cigarettes and alcohol versus cigarettes and marijuana among young adults using
      cross-sectional survey data. Methods: Participants were young adult cigarette
      smokers (age 18 to 25) who also reported past month alcohol or marijuana use
      enrolled in a randomized trial testing a smoking cessation intervention on
      Facebook. Participants self-reported extent of cigarette smoking under the
      influence of alcohol or marijuana and differences in perceived pleasure from
      cigarette smoking when drinking alcohol compared to using marijuana. Results:
      Among cigarette smokers who drank alcohol and used marijuana in the past month
      (n=200), a similar percentage of cigarettes were smoked under the influence of
      alcohol (42.4%+/-31.2%) and marijuana (43.1% +/-30.0%). Among alcohol + marijuana
      users, perceived pleasure from smoking cigarettes was significantly greater when
      drinking alcohol versus when using marijuana (t(199)=7.05, p<0.001). There was,
      on average, an increase in perceived pleasure from smoking cigarettes when
      drinking alcohol, though perceived pleasure did not differ by binge drinking
      frequency. In contrast, there was on average no change in perceived pleasure from
      smoking cigarettes when using marijuana. Results from the cigarette smokers who
      used alcohol + marijuana were similar to cigarette smokers who only used alcohol
      (n=158) or only used marijuana (n=54). Conclusion: Findings highlight greater
      perceived reward from smoking cigarettes when drinking alcohol compared to when
      using marijuana, informing smoking cessation interventions that target users of
      multiple substances.

PMID- 29371860
TI  - Corrigendum: Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin
      Resistant MCF-7 Breast Cancer Cells via NF-kappaB-Independent Mechanism.
AB  - [This corrects the article on p. 648 in vol. 8, PMID: 28959205.].

PMID- 29371861
TI  - Corrigendum: Phylogenetic Analyses of Shigella and Enteroinvasive Escherichia
      coli for the Identification of Molecular Epidemiological Markers: Whole-Genome
      Comparative Analysis Does Not Support Distinct Genera Designation.
AB  - [This corrects the article on p. 1573 in vol. 6, PMID: 26834722.].

PMID- 29371862
TI  - Corrigendum: Mannitol Stress Directs Flavonoid Metabolism toward Synthesis of
      Flavones via Differential Regulation of Two Cytochrome P450 Monooxygenases in
      Coleus forskohlii.
AB  - [This corrects the article on p. 985 in vol. 7, PMID: 27458469.].

PMID- 29371863
TI  - Body composition, adipokines, bone mineral density and bone remodeling markers in
      relation to IGF-1 levels in adults with Prader-Willi syndrome.
AB  - Background: In patients with Prader-Willi syndrome (PWS) body composition is
      abnormal and alterations in appetite regulating factors, bone mineral density and
      insulin-like growth factor-1 (IGF-1) levels have been described. Studies in PWS
      adults are limited. In this study, we investigated body composition, appetite
      regulating peptides, bone mineral density and markers of bone remodeling in an
      adult PWS population. Furthermore, we investigated the association between these
      different parameters and IGF-1 levels because of the described similarities with
      growth hormone deficient patients. Methods: In this cross-sectional observational
      cohort study in a university hospital setting we studied fifteen adult PWS
      patients. Anthropometric and metabolic parameters, IGF-1 levels, bone mineral
      density and bone metabolism were evaluated. The homeostasis model assessment of
      insulin resistance (HOMA2-IR) was calculated. Fourteen healthy siblings served as
      a control group for part of the measurements. Results: In the adult PWS patients,
      height, fat free mass, IGF-1 and bone mineral content were significantly lower
      when compared to controls; body mass index (BMI), waist, waist-to-hip ratio and
      fat mass were higher. There was a high prevalence of osteopenia and osteoporosis
      in the PWS patients. Also, appetite regulating peptides and bone remodelling
      markers were aberrant when compared to reference values. Measurements of body
      composition were significantly correlated to appetite regulating peptides and
      high-sensitive C-reactive protein (hs-CRP), furthermore HOMA was correlated to
      BMI and adipokines. Conclusion: In adults with Prader-Willi syndrome alterations
      in body composition, adipokines, hs-CRP and bone mineral density were
      demonstrated but these were not associated with IGF-1 levels. Further
      investigations are warranted to gain more insight into the exact pathophysiology
      and the role of these alterations in the metabolic and cardiovascular
      complications seen in PWS, so these complications can be prevented or treated as
      early as possible.

PMID- 29371865
TI  - Pulmonary artery banding using polytetrafluoroethylene; Choice of material.

PMID- 29371864
TI  - Onset of action for loratadine tablets for the symptomatic control of seasonal
      allergic rhinitis in adults challenged with ragweed pollen in the Environmental
      Exposure Unit: a post hoc analysis of total symptom score.
AB  - Background: Loratadine is a second-generation, non-sedating antihistamine used
      for the relief of allergic rhinitis symptoms. Previous studies reported that when
      loratadine was encapsulated, the onset of action for symptom relief was 180 min.
      However, unmodified loratadine tablets were not evaluated at that time. Using
      data from a previously published Environmental Exposure Unit (EEU) study
      comparing azelastine nasal spray with loratadine tablets, cetirizine tablets, and
      placebo, this post hoc analysis determines the onset of action of loratadine
      tablets (i.e. unmodified) by analyzing the total symptom score for the relief of
      nasal and ocular seasonal allergic rhinitis (SAR) symptoms. Methods: A Phase IV,
      randomized, single-center, double-blind, placebo-controlled, double-dummy, four
      way crossover study was conducted in the EEU. Seventy participants were
      randomized sequentially into one of the four treatments during ragweed pollen
      exposure. Nasal and ocular symptom scores were self-reported by the participants
      and recorded. The original study analysis was carried out by evaluating the nasal
      symptom scores only. For this post hoc analysis, both nasal and ocular data from
      the loratadine and placebo treatment arms were analyzed. The primary endpoint for
      this analysis was the onset of action of loratadine as measured by the change in
      total symptom score (TSS) from baseline in comparison to placebo. The onset of
      ocular symptom relief using the total ocular symptom score (TOSS) was also
      reported. Results: Loratadine tablets demonstrated a significant and durable
      improvement in both TSS (P = .005) and TOSS (P = .013) at 75 min post-treatment
      administration compared to placebo. The mean proportion of participants reporting
      none or mild for all component symptoms of TSS and TOSS at 75 min and thereafter
      was significantly higher in the loratadine (TSS, P = .0005; TOSS, P <= .0001) vs.
      placebo treatment arm. Conclusions: The onset of action of loratadine tablets was
      75 min for the relief of nasal and ocular symptoms in adults with SAR. These
      results suggest a faster onset of action for loratadine tablets (75 min) compared
      to previously reported studies which were conducted with modified (i.e. gelatin
      encapsulated) loratadine tablets (180 min).Trial registration Clinicaltrials.gov
      identifier NCT00561717.

PMID- 29371866
TI  - Gensini scores and well-being states among patients with coronary artery disease:
      A comparison study.
AB  - BACKGROUND: World Health Organization (WHO) considered Mental Health Continuum
      (MHC) as a good instrument for well-being studies. Moreover, gensini score (GS)
      is an intensity index for coronary artery disease (CAD). The aim of our study was
      to compare GSs among patients who had coronary artery disease with different well
      being states. METHODS: This was a cross-sectional study conducted in Tehran Heart
      Center, Iran, in 2013. The study population consisted of 50 non-depressed
      patients who were candidates for coronary artery bypass graft (CABG). All of the
      participants were interviewed according to the Iranian version of Mental Health
      Continuum (IV-MHC) and were allocated to flourishing, maternal mental health
      (MMH) and languishing states based on the related classification criteria. GS was
      calculated for each participant. Data were analyzed by SPSS. RESULTS: Forty one
      (82%) patients were in flourishing, 9 (18%) in MMH and nobody was in languishing
      states. The mean (standard deviation) of GS was 90.43 (44.424) and 89.67 (33.378)
      for flourishing and MMH ones, respectively (P = 0.962). There was no
      statistically significant correlation between GSs and well-being states (all Ps >
      0.050). CONCLUSION: Considering IV-MHC classification, all of our patients were
      only allocated to flourishing and MMH states. There was no relationship between
      intensity of CAD and the states (P > 0.050). We recommend further research with
      larger sample sizes for better evaluation of the Iranian version of the
      instrument.

PMID- 29371867
TI  - Design and implementation of a combined observational and interventional study:
      Trends of prevalence, awareness, treatment and control hypertension and the
      effect of expanded chronic care model on control, treatment and self-care.
AB  - BACKGROUND: Lack of information about hypertension leads to failure in detection,
      treatment and reduced estimation of this disease effects. So, a comprehensive
      study, named trends of prevalence, awareness, treatment and control hypertension
      among the adults in Isfahan, Iran (2001-2016) and evaluation of the effect of
      expanded chronic care model (ECCM) on control, treatment and self-care, has been
      designed. This study explains the aspects of design and methods of its
      implementation. METHODS: This study was conducted in four stages in 2014-2016. In
      the 1st stage, valid questionnaires were made to assess knowledge, attitude and
      practice, and self-care. In the 2nd stage, the status of prevalence, awareness,
      treatment and control and hypertension risk factors was assessed. In the 3rd
      stage, a two-group clinical trial was conducted to evaluate the effectiveness of
      ECCM on hypertensive patients and their families. In the 4th stage, the results
      of hypertension prevalence and its risk factors in adults in 2016 were compared
      with two other studies undertaken in 2001 and 2007. RESULTS: To develop the
      questionnaire, face and content validity, internal and external reliability, and
      construct validity were examined. Prevalence, awareness, treatment and control of
      hypertension and risk factors among 2107 adult individuals were determined in
      Isfahan. In a clinical trial, 216 hypertensive patients were randomly assigned
      into intervention and control groups. Finally, a sample size of 8073 people was
      used to determine and compare the 15-year-old trend of hypertension and its
      affecting factors. CONCLUSION: It is obvious that the final findings of this
      study will play a key role in health and research policy and provide a suitable
      model for implementing appropriate interventional measures at the provincial and
      national levels.

PMID- 29371868
TI  - Factors associated with the no-reflow phenomenon following percutaneous
      intervention of saphenous vein coronary bypass grafts.
AB  - BACKGROUND: We investigated clinical and procedural factors associated with the
      no-reflow phenomenon following percutaneous coronary intervention (PCI) of the
      saphenous-vein grafts (SVG). METHODS: A cross-sectional study was done on
      patients who had undergone PCI of the SVG. Patients' medical documents were
      reviewed for demographic, clinical, laboratory, and procedural data. Slow/no
      reflow was defined based on the thrombolysis in myocardial infarction (TIMI)
      grade (0 to 2). Univariate and multiple logistic regression analyses were
      performed to investigate factors associated with slow/no-reflow and P < 0.050 was
      considered as significant. RESULTS: A total of 205 patients were studied (81%
      man, mean +/- standard deviation of age was 66.8 +/- 9.6 years). Slow/no-reflow
      was found in 38 (18.5%) patients. High diastolic blood pressure (P = 0.010),
      leukocytosis (P = 0.017), diffuse lesions (P = 0.007), degenerated SVG (P <
      0.001), proximal lesions (P < 0.001), thrombosis (P = 0.013), and lower number of
      used stents during procedure (P = 0.032) were associated with slow/no-reflow in
      unadjusted analyses. Factors independently associated with slow/no-reflow were
      pre-procedural high diastolic blood pressure with odds ratio (OR) = 3.858 [95%
      confidence interval (95% CI), 1.157-12.860], degenerated SVG with OR = 5.901 (95%
      CI: 1.883-18.492), proximal lesions with OR = 5.070 (95% CI: 1.822-14.113), pre
      intervention TIMI grade with OR = 0.618 (95% CI: 0.405-0.942), number of used
      stents for PCI with OR = 0.074 (95% CI: 0.011-0.481) for > 1 stent, and length of
      stents used for PCI with OR = 0.100 (95% CI: 0.019-0.529) for > 30 mm stents.
      CONCLUSION: This study on the clinical and procedural factors associated with the
      slow/no-reflow phenomenon following PCI of the SVG can be used in risk estimation
      of this serious complication and tailoring preventive strategies to at-risk
      patients.

PMID- 29371869
TI  - Allopurinol prophylactic therapy and the prevention of contrast-induced
      nephropathy in high-risk patients undergoing coronary angiography: A prospective
      randomized controlled trial.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is considered to be a possibly
      severe complication of radiography and thus, remains to be the main cause of
      acute kidney injury (AKI) for inpatients. A clinical trial was executed to
      measure the preventive effect of allopurinol against CIN in high-risk patients
      undertaking coronary angiography. METHODS: Through randomized controlled trial,
      140 patients with at minimum two risk factors of CIN, undertaking coronary
      angiography, were randomly allocated to the allopurinol (n = 70) or control group
      (n = 70). Those in the allopurinol group received allopurinol (300 mg) a day
      before their coronary angiography and intravenous hydration for 12 hours before
      and after their procedure, while members of the control group only received
      intravenous hydration. Serum creatinine (SCr), blood urea nitrogen (BUN) and uric
      acid were measured before and 48 hours after the procedure. CIN was defined by a
      25% increase in SCr or the concentration of > 0.5 mg/dl, 48 hours after coronary
      angiography. RESULTS: CIN was observed in 8 (11.4%) patients in the allopurinol
      group and 11 (15.7%) patients in the control group. There was no significant
      difference in the incidence of CIN between the two groups at 48 hours after
      coronary angiography (P = 0.459). In the allopurinol group, the median SCr
      concentration decreased non-significantly from 1.16 mg/dl to 1.13 mg/dl, 48 hours
      after coronary angiography (P = 0.189). In the control group, the median SCr
      concentration increased significantly from 1.11 mg/dl to 1.2 mg/dl, 48 hours
      after coronary angiography (P < 0.001). CONCLUSION: Allopurinol presents no
      considerable effectiveness over the hydration protocol for development of CIN in
      high-risk patients.

PMID- 29371870
TI  - Persian Registry Of cardioVascular diseasE (PROVE): Design and methodology.
AB  - BACKGROUND: Our aim was to create and establish a database called "Persian
      Registry Of cardioVascular diseasE (PROVE)" in order to be used for future
      research and in addition, as a tool to develop national guidelines for diagnosis,
      treatment, and prevention of cardiovascular disease (CVD). In this paper, the
      design and methodology of the PROVE pilot study will be discussed, launched in
      Isfahan, Iran, in 2015-2016. METHODS: Through establishing PROVE, patients' data
      were collected from hospitals and outpatient clinics prospectively or
      retrospectively and followed up for a maximum of three years based on the type of
      CVDs. The inclusion criteria were as patients with acute coronary syndrome (ACS),
      ST elevation myocardial infarction (STEMI), stroke, atrial fibrillation (AF),
      heart failure (HF), congenital heart disease (CHD), percutaneous coronary
      intervention (PCI), and chronic ischemic cardiovascular disease (CICD). Specific
      protocols, questionnaires, and glossaries were developed for each registry. In
      order to ensure the validation of the protocols, questionnaires, data collection,
      management, and analysis, a well-established quality control (QC) protocol was
      developed and implemented. Data confidentiality was considered. RESULTS: In order
      to register patients with ACS, STEMI, stroke, HF, PCI, and CICD, the hospital
      recorded data were used, whereas, in case of AF and CHD registries, the data were
      collected from hospitals and outpatient clinics. During the pilot phase of the
      study in Isfahan, from March 2015 to September 2016, 9427 patients were
      registered as ACS including 809 as STEMI, 1195 patients with HF, 363 with AF, 761
      with stroke, 1136 with CHD, 1200 with PCI, and 9 with CICD. Data collection and
      management were performed under the supervision of the QC group. CONCLUSION:
      PROVE was developed and implemented in Isfahan as a pilot study, in order to be
      implemented at national level in future. It provides a valuable source of valid
      data that could be used for future research, re-evaluation of current CVD
      management and more specifically, gap analysis and as a tool for assessment of
      the type of CVDs, prevention, treatment, and control by health care decision
      makers.

PMID- 29371871
TI  - Effect of crocin, a carotenoid from saffron, on plasma cholesteryl ester transfer
      protein and lipid profile in subjects with metabolic syndrome: A double blind
      randomized clinical trial.
AB  - BACKGROUND: Metabolic syndrome is defined by insulin resistance and a clustering
      of other cardiovascular risk factors. Crocin is a carotenoid derived from the
      stigmas of the saffron flower and had previously been shown to affect lipid
      profile. However, the mechanism for this function is not well understood. The
      present trial aimed to investigate the possible effect of crocin on plasma levels
      of cholesteryl ester transfer protein and lipid profile in individuals with
      metabolic syndrome. METHODS: This was a randomized, double-blind, placebo
      controlled, clinical trial consisting of an 8-week treatment with crocin, or
      placebo tablets between April and June 2014, in the Nutrition Clinic of Ghaem
      Teaching Hospital, Mashhad, Iran. Participants were randomly assigned to take a
      30 mg/day crocin (n = 22) in the intervention group or placebo (n = 22) in the
      control group. Anthropometric, hematological and biochemical parameters were
      measured and recorded during pre and post-treatment periods. RESULTS: Whilst
      plasma cholesteryl ester transfer protein was increased in the group taking the
      crocin tablet by 27.81% during the trial period (P = 0.013), the difference
      between the crocin and placebo groups was not significant (P = 0.116). Moreover,
      the percent changes in cholesterol (P = 0.702), triglyceride (P = 0.080), low
      density lipoprotein (LDL) (P = 0.986), high-density lipoprotein (HDL) (P = 0.687)
      and fasting blood glucose (P = 0.614) did not differ significantly between
      intervention and control groups. CONCLUSION: Although crocin supplements
      increased the serum cholesteryl ester transfer protein in patients with metabolic
      syndrome, this change was not significant between treatment and placebo groups.

PMID- 29371872
TI  - Septal hematoma due to stent implementation in the septal course of the left
      anterior descending artery.
AB  - BACKGROUND: The interventricular septal hematoma (IVSH) is a rare and potentially
      lethal finding. There are variously reported etiologies including instrumental
      damages during cardiac interventions. Although there are not enough studies
      available, conservative management is considered as a preferable approach in
      stable patients. CASE REPORT: A 45-year man smoker with the previous history of
      percutaneous coronary intervention (PCI), admitted with unstable angina in
      present visit. Coronary angiography showed significant in-stent restenosis (ISR)
      of the left anterior descending (LAD) artery stent. During our intervention for
      treatment of the ISR, the wire movement caused a diffuse dissection without any
      runoff, in the distal portion of the LAD. Therefore two stents were deployed in
      the dissected segment with a short overlapping segment. Unfortunately, the
      overlapping segment of these stents was located in the myocardial bridge segment.
      Therefore the contraction of the interventricular septum (IVS) caused a scissor
      like movement of the stents, and they ruptured the LAD into the septum.
      Therefore, the contrast agent was accumulated in the IVS. Immediately, a graft
      stent was deployed in the overlapping segment of stents and perforation became
      sealed. In echocardiography, the IVS diameter increased to 30 mm. Since the
      patient was hemodynamically and electrically stable, he underwent conservative
      approach and after two months the septum returned to the normal size. CONCLUSION:
      During PCI on the LAD artery, the implantation of stents in the septal course
      with a short overlapping segment can result in coronary perforation, and
      therefore IVS hematoma by the scissor effect. Septal hematoma may cause life
      threatening arrhythmias or ventricular septal rupture, but if it is asymptomatic
      or uncomplicated. Conservative management is the best strategy.

PMID- 29371873
TI  - The common use of improper control diets in diet-induced metabolic disease
      research confounds data interpretation: the fiber factor.
AB  - Diets used to induce metabolic disease are generally high in fat and refined
      carbohydrates and importantly, are usually made with refined, purified
      ingredients. However, researchers will often use a low fat grain-based (GB) diet
      containing unrefined ingredients as the control diet. Such a comparison between
      two completely different diet types makes it impossible to draw conclusions
      regarding the phenotypic differences driven by diet. While many compositional
      differences can account for this, one major difference that could have the
      greatest impact between GB and purified diets is the fiber content, both in terms
      of the level and composition. We will review recent data showing how fiber
      differences between GB diets and purified diets can significantly influence gut
      health and microbiota, which itself can affect metabolic disease development.
      Researchers need to consider the control diet carefully in order to make the best
      use of precious experimental resources.

PMID- 29371874
TI  - Z-ligustilide and anti-inflammatory prostaglandins have common biological
      properties in macrophages and leukocytes.

PMID- 29371876
TI  - 'The mum has to live with the decision much more than the dad'; a qualitative
      study of men's perceptions of their influence on breastfeeding decision-making.
AB  - Background: Although breastfeeding is widely acknowledged as the normal method of
      infant feeding, there are large variations in rates of initiation and duration.
      Several factors are linked to the likelihood of breastfeeding initiation,
      including the influence and opinion of the child's father. There is limited
      research into men's perception of their influence, or if they feel it appropriate
      to be involved in deciding how to feed their children. The aim of this study was
      to investigate, using a qualitative methodology, fathers' perceptions of their
      influence on the decision to feed their child breastmilk or formula. Methods: Six
      men were recruited through Children's Centres in Bristol, United Kingdom, and a
      phenomenological research methodology implemented using semi-structured
      interviews. Specific objectives were: to understand participants' views on
      breastfeeding; understand if and how these views were discussed with their
      partner; to determine if participants believed involvement in the feeding
      decision is appropriate; to understand how they felt about the decision made; and
      to see if their views changed after the birth of their child. Results: Multiple
      themes emerged during analysis, including deferring of responsibility to the
      mother; breastfeeding as normal practice; change in attitude; involvement in
      parenting; and, advantages for the father. The men in the study accepted
      breastfeeding as normal behaviour, probably because of their upbringing in
      households where breastfeeding was practiced. There was consensus that women had
      more say in deciding to breastfeed, which was explained as a consequence of their
      greater involvement. It could also be interpreted as an unwillingness to
      interfere in an area perceived as 'owned' by women. Participants acknowledged
      that breastfeeding was more difficult than they had perceived. Conclusions: The
      key themes emerging from the interviews are suggestive of an impact on
      breastfeeding interventions that use the father as an intermediary. If they do
      not feel that they are 'permitted' to comment on their partner's breastfeeding,
      then simply increasing knowledge of breastfeeding benefits in these men is likely
      to have minimal impact.

PMID- 29371877
TI  - Using k-NN to analyse images of diverse germination phenotypes and detect single
      seed germination in Miscanthus sinensis.
AB  - Background: Miscanthus is a leading second generation bio-energy crop. It is
      mostly rhizome propagated; however, the increasing use of seed is resulting in a
      greater need to investigate germination. Miscanthus seed are small, germination
      is often poor and carried out without sterilisation; therefore, automated methods
      applied to germination detection must be able to cope with, for example,
      thresholding of small objects, low germination frequency and the presence or
      absence of mould. Results: Machine learning using k-NN improved the scoring of
      different phenotypes encountered in Miscanthus seed. The k-NN-based algorithm was
      effective in scoring the germination of seed images when compared with human
      scores of the same images. The trueness of the k-NN result was 0.69-0.7, as
      measured using the area under a ROC curve. When the k-NN classifier was tested on
      an optimised image subset of seed an area under the ROC curve of 0.89 was
      achieved. The method compared favourably to an established technique.
      Conclusions: With non-ideal seed images that included mould and broken seed the k
      NN classifier was less consistent with human assessments. The most accurate
      assessment of germination with which to train classifiers is difficult to
      determine but the k-NN classifier provided an impartial consistent measurement of
      this important trait. It was more reproducible than the existing human scoring
      methods and was demonstrated to give a high degree of trueness to the human
      score.

PMID- 29371875
TI  - Psychopathology of addiction: Can the SCL90-based five-dimensional structure
      differentiate Heroin Use Disorder from a non-substance-related addictive disorder
      such as Gambling Disorder?
AB  - Background: In the Gambling Disorder (GD), there is no exogenous drug
      administration that acts as the central core of the traditional meaning of
      addiction. A specific psychopathology of Substance Use Disorders has been
      proposed recently. In a sample of Heroin Use Disorder (HUD) patients entering
      opioid agonist treatment, it became possible to identify a group of 5 mutually
      exclusive psychiatric dimensions: Worthlessness-Being trapped (W-BT), Somatic
      Symptoms (SS), Sensitivity-Psychoticism (SP), Panic Anxiety (PA) and Violence
      Suicide (VS). The specificity of these dimensions was suggested by the absence of
      their correlations with treatment choice, active substance use, psychiatric
      comorbidity and the principal substance of abuse and by the opportunity, through
      their use, of fully discriminating HUD from Major Depression patients and,
      partially, from obese non-psychiatric patients. To further support this
      specificity in the present study, we tested the feasibility of discriminating HUD
      patients from those affected by a non-substance-related addictive behaviour, such
      as GD. In this way, we also investigated the psychopathological peculiarities of
      GD patients. Methods: We compared the severity and frequency of each of the five
      aspects found by us, in 972 (83.5% males; mean age 30.12 +/- 6.6) HUD and 110
      (50% males; average age 30.12 +/- 6.6) GD patients at univariate (T test; Chi
      square) and multivariate (discriminant analysis and logistic regression) level.
      Results: HUD patients showed higher general psychopathology indexes than GD
      patients. The severity of all five psychopathological dimensions was
      significantly greater in HUD patients. Discriminant analysis revealed that SS and
      VS severity were able to discriminate between HUD (higher severity) and GD
      patients (lower severity), whereas PA and SP could not. W-BT severity was
      negatively correlated with SS and VS; GD patients were distinguished by low
      scores for SS and VS low scores associated with high ones for W-BT.
      Psychopathological subtypes characterized by SS and VS symptomatology were better
      represented in HUD patients, whereas PA symptomatology was more frequent in GD
      individuals. No differences were observed regarding the W-BT and SP dimensions.
      At multivariate level, the one prominent characteristic of HUD patients was the
      presence of SS (OR = 5.43) as a prominent qualification for psychopathological
      status. Conclusions: Apart from the lower severity of all psychopathological
      dimensions, only the lower frequency of SS typology seems to be the prominent
      factor in GD patients. The SCL90-defined structure of opioid addiction seems to
      be useful even in non-substance-related addictive disorders, as in the case of GD
      patients, further supporting the possible existence of a psychopathology specific
      to addiction.

PMID- 29371878
TI  - Establishing position papers by the WSES.
AB  - A position paper (PP) should establish a unified voice in areas where controversy
      occurs based upon multiple practices and/or therapeutic choices. Typically, a
      position paper should elucidate the knowledge gap, followed by an evidence-based
      review of options, leading to an "endorsed position." A position paper should
      represent more than the opinion or consensus of the authors but should present
      current opinions and practices supported by the World Society of Emergency
      Surgery (WSES). Accordingly, position papers should require the approval of an
      expert group of WSES and in parallel be presented at an annual meeting prior to
      submission for publication. It is important that a unified approach for drafting
      of position papers be established and endorsed by WSES in order to establish
      credibility and prevent misunderstandings during a smooth transition to
      publication. The purpose of this article is to suggest a uniform process for the
      development of WSES guidelines.

PMID- 29371879
TI  - Casualties of peace: an analysis of casualties admitted to the intensive care
      unit during the negotiation of the comprehensive Colombian process of peace.
AB  - Background: After 52 years of war in 2012, the Colombian government began the
      negotiation of a process of peace, and by November 2012, a truce was agreed. We
      sought to analyze casualties who were admitted to the intensive care unit (ICU)
      before and during the period of the negotiation of the comprehensive Colombian
      process of peace. Methods: Retrospective study of hostile casualties admitted to
      the ICU at a Level I trauma center from January 2011 to December 2016. Patients
      were subsequently divided into two groups: those seen before the declaration of
      the process of peace truce (November 2012) and those after (November 2012
      December 2016). Patients were compared with respect to time periods. Results:
      Four hundred forty-eight male patients were admitted to the emergency room. Of
      these, 94 required ICU care. Sixty-five casualties presented before the truce and
      29 during the negotiation period. Median injury severity score was significantly
      higher before the truce. Furthermore, the odds of presenting with severe trauma
      (ISS > 15) were significantly higher before the truce (OR, 5.4; (95% CI, 2.0
      14.2); p < 0.01). There was a gradual decrease in the admissions to the ICU, and
      the performance of medical and operative procedures during the period observed.
      Conclusion: We describe a series of war casualties that required ICU care in a
      period of peace negotiation. Despite our limitations, our study presents a
      decline in the occurrence, severity, and consequences of war injuries probably as
      a result in part of the negotiation of the process of peace. The hysteresis of
      these results should only be interpreted for their implications in the
      understanding of the peace-health relationship and must not be overinterpreted
      and used for any political end.

PMID- 29371881
TI  - Improving the capacity of community-based workers in Australia to provide initial
      assistance to Iraqi refugees with mental health problems: an uncontrolled
      evaluation of a Mental Health Literacy Course.
AB  - Background: Australia is a multicultural nation with a humanitarian program that
      welcomes a large number of Iraqi refugees. Despite the high prevalence of trauma
      related disorders, professional help-seeking in this group is very low. This
      study sought to evaluate a face-to-face mental health literacy (MHL) Course that
      teaches community-based workers how to provide initial help to Iraqi refugees
      with depression and post-traumatic stress disorder (PTSD) related problems.
      Methods: An uncontrolled pre, post and follow-up design was used to measure
      improvement in MHL in community-based workers assisting Iraqi refugees. Results:
      Eighty-six participants completed the pre- and post-training questionnaires.
      Forty-five (52%) completed all 3-time point questionnaires. Fifty-six percent
      (48/86) of participants were able to correctly recognise 'PTSD' as the problem
      depicted in a vignette before the training. This increased to 77% (66/86) after
      training and was maintained at follow-up with 82% (37/45) correctly recognising
      the problem (p = 0.032). Recognition of depression also increased from 69%
      (59/86) at pre-training to 83% (71/86) after training and to 82% (37/45) at
      follow-up. There was a significant increase in perceived helpfulness of
      professional treatments for depression after training (p < 0.001 at post
      training, p = 0.010 at follow-up). Significant changes were reported in
      confidence of participants when helping an Iraqi refugee with PSTD (p < 0.001 at
      post-training, p < 0.001 at follow-up) and depression (p < 0.001 at post
      training, p = 0.003 at follow-up). A decrease were also found on social distance
      mean scores associated with PTSD (p = 0.006 at post-training, p < 0.001 at follow
      up) and depression (p = 0.007 at follow-up). Changes were not significant
      following training for offering help and helping behaviours in both PSTD and
      depression vignettes and, the 'dangerous/unpredictable' subscale in the
      depression vignette. Conclusion: This training is a recommendable way to improve
      and better equip staff on how to respond to mental health crises and offer Mental
      Health First Aid in a culturally sensitive manner to Iraqi refugees.

PMID- 29371880
TI  - Dissecting the mechanisms and molecules underlying the potential carcinogenicity
      of red and processed meat in colorectal cancer (CRC): an overview on the current
      state of knowledge.
AB  - Meat is a crucial nutrient for human health since it represents a giant supply of
      proteins, minerals, and vitamins. On the opposite hand, the intake of red and
      processed meat is taken into account dangerous due to its potential of
      carcinogenesis and cancer risk improvement, particularly for colorectal cancer
      (CRC), although it has been reported that also the contaminations of beef
      infected by oncogenic bovine viruses could increase colorectal cancer's risk.
      Regarding the mechanisms underlying the potential carcinogenicity of red and
      processed meat, different hypotheses have been proposed. A suggested mechanism
      describes the potential role of the heterocyclic amines (HACs) and polycyclic
      aromatic hydrocarbons (PHAs) in carcinogenesis induced by DNA mutation. Another
      hypothesis states that heme, through the lipid peroxidation process and therefore
      the formation of N-nitroso compounds (NOCs), produces cytotoxic and genotoxic
      aldehydes, resulting in carcinogenesis. Furthermore, a recent proposed
      hypothesis, is based on the combined actions between the N-Glycolylneuraminic
      acid (Neu5Gc) and genotoxic compounds. The purpose of this narrative review is to
      shed a light on the mechanisms underlying the potential carcinogenicity of red
      and processed meat, by summarizing the data reported in literature on this topic.

PMID- 29371882
TI  - Thematic series CAPMH "Forensic Child and Adolescent Psychiatry and Mental Health
      2017".

PMID- 29371883
TI  - Conversion of lignocellulosic agave residues into liquid biofuels using an AFEXTM
      based biorefinery.
AB  - Background: Agave-based alcoholic beverage companies generate thousands of tons
      of solid residues per year in Mexico. These agave residues might be used for
      biofuel production due to their abundance and favorable sustainability
      characteristics. In this work, agave leaf and bagasse residues from species Agave
      tequilana and Agave salmiana were subjected to pretreatment using the ammonia
      fiber expansion (AFEX) process. The pretreatment conditions were optimized using
      a response surface design methodology. We also identified commercial enzyme
      mixtures that maximize sugar yields for AFEX-pretreated agave bagasse and leaf
      matter, at ~ 6% glucan (w/w) loading enzymatic hydrolysis. Finally, the
      pretreated agave hydrolysates (at a total solids loading of ~ 20%) were used for
      ethanol fermentation using the glucose- and xylose-consuming strain Saccharomyces
      cerevisiae 424A (LNH-ST), to determine ethanol yields at industrially relevant
      conditions. Results: Low-severity AFEX pretreatment conditions are required (100
      120  degrees C) to enable efficient enzymatic deconstruction of the agave cell
      wall. These studies showed that AFEX-pretreated A. tequilana bagasse, A.
      tequilana leaf fiber, and A. salmiana bagasse gave ~ 85% sugar conversion during
      enzyme hydrolysis and over 90% metabolic yields of ethanol during fermentation
      without any washing step or nutrient supplementation. On the other hand, although
      lignocellulosic A. salmiana leaf gave high sugar conversions, the hydrolysate
      could not be fermented at high solids loadings, apparently due to the presence of
      natural inhibitory compounds. Conclusions: These results show that AFEX
      pretreated agave residues can be effectively hydrolyzed at high solids loading
      using an optimized commercial enzyme cocktail (at 25 mg protein/g glucan)
      producing > 85% sugar conversions and over 40 g/L bioethanol titers. These
      results show that AFEX technology has considerable potential to convert
      lignocellulosic agave residues to bio-based fuels and chemicals in a biorefinery.

PMID- 29371884
TI  - In vivo selection of sfGFP variants with improved and reliable functionality in
      industrially important thermophilic bacteria.
AB  - Background: Fluorescent reporter proteins (FP) have become an indispensable tool
      for the optimization of microbial cell factories and in synthetic biology per se.
      The applicability of the currently available FPs is, however, constrained by
      species-dependent performance and misfolding at elevated temperatures. To obtain
      functional reporters for thermophilic, biotechnologically important bacteria such
      as Parageobacillus thermoglucosidasius, an in vivo screening approach based on a
      mutational library of superfolder GFP was applied. Results: Flow cytometry-based
      benchmarking of a set of GFPs, sfGFPs and species-specific codon-optimized
      variants revealed that none of the proteins was satisfyingly detectable in P.
      thermoglucosidasius at its optimal growth temperature of 60  degrees C. An
      undirected mutagenesis approach coupled to fluorescence-activated cell sorting
      allowed the isolation of sfGFP variants that were extremely well expressed in the
      chassis background at 60  degrees C. Notably, a few nucleotide substitutions,
      including silent mutations, significantly improved the functionality and
      brightness. The best mutant sfGFP(N39D/A179A) showed an 885-fold enhanced mean
      fluorescence intensity (MFI) at 60  degrees C and is the most reliable reporter
      protein with respect to cell-to-cell variation and signal intensity reported so
      far. The in vitro spectral and thermostability properties were unaltered as
      compared to the parental sfGFP protein, strongly indicating that the combination
      of the amino acid exchange and an altered translation or folding speed, or
      protection from degradation, contribute to the strongly improved in vivo
      performance. Furthermore, sfGFP(N39D/A179A) and the newly developed cyan and
      yellow derivatives were successfully used for labeling several industrially
      relevant thermophilic bacilli, thus proving their broad applicability.
      Conclusions: This study illustrates the power of in vivo isolation of
      thermostable proteins to obtain reporters for highly efficient fluorescence
      labeling. Successful expression in a variety of thermophilic bacteria proved that
      the novel FPs are highly suitable for imaging and flow cytometry-based studies.
      This enables a reliable cell tracking and single-cell-based real-time monitoring
      of biological processes that are of industrial and biotechnological interest.

PMID- 29371885
TI  - Working towards recalcitrance mechanisms: increased xylan and homogalacturonan
      production by overexpression of GAlactUronosylTransferase12 (GAUT12) causes
      increased recalcitrance and decreased growth in Populus.
AB  - Background: The development of fast-growing hardwood trees as a source of
      lignocellulosic biomass for biofuel and biomaterial production requires a
      thorough understanding of the plant cell wall structure and function that
      underlie the inherent recalcitrance properties of woody biomass. Downregulation
      of GAUT12.1 in Populus deltoides was recently reported to result in improved
      biomass saccharification, plant growth, and biomass yield. To further understand
      GAUT12.1 function in biomass recalcitrance and plant growth, here we report the
      effects of P. trichocarpa GAUT12.1 overexpression in P. deltoides. Results:
      Increasing GAUT12.1 transcript expression by 7-49% in P. deltoides PtGAUT12.1
      overexpression (OE) lines resulted in a nearly complete opposite biomass
      saccharification and plant growth phenotype to that observed previously in
      PdGAUT12.1-knockdown (KD) lines. This included significantly reduced glucose,
      xylose, and total sugar release (12-13%), plant height (6-54%), stem diameter (8
      40%), and overall total aerial biomass yield (48-61%) in 3-month-old, greenhouse
      grown PtGAUT12.1-OE lines compared to controls. Total lignin content was
      unaffected by the gene overexpression. Importantly, selected PtGAUT12.1-OE lines
      retained the recalcitrance and growth phenotypes upon growth for 9 months in the
      greenhouse and 2.8 years in the field. PtGAUT12.1-OE plants had significantly
      smaller leaves with lower relative water content, and significantly reduced stem
      wood xylem cell numbers and size. At the cell wall level, xylose and galacturonic
      acid contents increased markedly in total cell walls as well as in soluble and
      insoluble cell wall extracts, consistent with increased amounts of xylan and
      homogalacturonan in the PtGAUT12.1-OE lines. This led to increased cell wall
      recalcitrance, as manifested by the 9-15% reduced amounts of recovered
      extractable wall materials and 8-15% greater amounts of final insoluble pellet in
      the PtGAUT12.1-OE lines compared to controls. Conclusions: The combined phenotype
      and chemotype data from P. deltoides PtGAUT12.1-OE and PdGAUT12.1-KD transgenics
      clearly establish GAUT12.1 as a recalcitrance- and growth-associated gene in
      poplar. Overall, the data support the hypothesis that GAUT12.1 synthesizes either
      an HG-containing primer for xylan synthesis or an HG glycan required for proper
      xylan deposition, anchoring, and/or architecture in the wall, and the possibility
      of HG and xylan glycans being connected to each other by a base-sensitive
      covalent linkage.

PMID- 29371886
TI  - Laccase-derived lignin compounds boost cellulose oxidative enzymes AA9.
AB  - Background: The discovery of lignin as activator for the redox enzyme lytic
      polysaccharide monooxygenases (LPMOs) for the oxidation of cell-wall
      polysaccharides opens a new scenario for investigation of the interplay between
      different lignocellulose-degrading enzymes. The lignin-active enzymes in one
      hand, and the carbohydrate active in the other, are linked through a variety of
      electrons carrier molecules either derived from lignin or enzymatically
      transferred. Likewise, in nature, many lignocellulose-degrading organisms are
      expressing those enzymes simultaneously, and we wanted to test if a major
      commercial available lignin oxidase enzyme, i.e., laccase could benefit and
      synergize the activity of the LPMOs by depolymerizing the insoluble lignin.
      Results: In this work, two fungal laccases together with a mediator (ABTS) were
      used to isolate low-molecular-weight lignin from lignocellulosic biomass. The
      isolated lignins were used as electron donors for activation of LPMOs. A direct
      correlation between the low-molecular-weight lignin isolated with laccases and an
      increased activity of a cellulolytic cocktail containing LPMO was found when pure
      cellulose was hydrolyzed. We then tried to implement existing commercial
      cellulases cocktail with laccase enzymes, but under the conditions tested, the co
      incubation of laccases with LPMOs showed a substrate competition towards oxygen
      inhibiting the LPMO. In addition, we found that laccase treatment may cause other
      modifications to pure cellulose, rendering the material more recalcitrant for
      enzymatic saccharification. Conclusions: Laccase-mediated system was able to
      depolymerize lignin from pre-treated and native sugarcane bagasse and wheat
      straw, and the released phenolic molecules were able to donate electrons to LPMO
      enzymes boosting the overall enzymatic hydrolysis of cellulose. Likewise, other
      poly-phenol oxidase, we might have just started showing possible pros or cons in
      applying several oxidase enzymes for a simultaneous degradation of cellulose and
      lignin, and we found that the competition towards oxygen and their different
      consumption rates must be taken into account for any possible co-application.

PMID- 29371887
TI  - Is cancer progression caused by gradual or simultaneous acquisitions of new
      chromosomes?
AB  - Background: Foulds defined, "Tumor progression (as a) permanent, irreversible
      qualitative change in one or more of its characters" (Cancer Res. 1954).
      Accordingly progressions, such as metastases and acquired drug-resistance, were
      since found to be subspecies of cancers with conserved and numerous new
      chromosomes. Here we ask whether cancers acquire numerous new chromosomes
      gradually or simultaneously in progressions. The currently prevailing theory of
      Nowell (Science, 1976) holds that unexplained "genetic instability" generates
      "variant sublines (with) changes in chromosome number" and that "clonal"
      progressions arise by "stepwise selection of more aggressive sublines". The
      literature, however, contains many examples of "immediate" selections of
      progressions with numerous new chromosomes - notably experimentally initiated
      fusions between cancers and heterologous cells. Furthermore, the stepwise
      progression theory predicts intermediate sublines of cancers with multiple non
      clonal additions of new chromosomes. However, the literature does not describe
      such intermediates. Results: In view of these inconsistencies with stepwise
      progression we test here a saltational theory, in which the inherent variability
      of cancer-specific aneuploidy generates "immediate" progressions with individual
      clonal karyotypes, transcriptomes and phenotypes in single steps. Using cell
      fusion as an established controllable model of "immediate" progression, we
      generated seven immortal murine hybridomas by fusing immortal murine myeloma
      cells and normal antibody-producing B-cells with polyethylene glycol within a few
      minutes. These immortal hybridomas contained individual sets of 71 to 105 clonal
      chromosomes, compared to the 52 chromosomes of the parental myeloma. Thus the
      myeloma had gained 19 to 53 new clonal chromosomes in seven individual hybridomas
      in a single step. Furthermore, no stable intermediates were found, as would be
      predicted by a saltational process. Conclusions: We conclude that random fusions
      between myelomas and normal B-cells generate clonal hybridomas with multiple,
      individual chromosomes in single steps. Similar single-step mechanisms may also
      generate the "late" clonal progressions of cancers with gains of numerous new
      chromosomes and thus explain the absence of intermediates. Latency would reflect
      the low probability of rare stochastic progressions. In conclusion, the
      karyotypic clonality of hybridomas and spontaneous progressions suggests
      karyotypic alterations as proximate causes of neoplastic progressions. Since
      cancer-specific aneuploidy catalyzes karyotypic variation, the degree of
      aneuploidy predicts the clinical risk of neoplastic progression, confirming
      classical predictions based on DNA content.

PMID- 29371888
TI  - Identification of genomic copy number variations associated with specific
      clinical features of head and neck cancer.
AB  - Background: Copy number variations (CNSs) of large genomic regions are an
      important mechanism implicated in the development of head and neck cancer,
      however, for most changes their exact role is not well understood. The aim of
      this study was to find possible associations between gains/losses of genomic
      regions and clinically distinct subgroups of head and neck cancer patients.
      Results: Array comparative genomic hybridization (aCGH) analysis was performed on
      DNA samples in 64 patients with cancer in oral cavity, oropharynx or hypopharynx.
      Overlapping genomic regions created from gains and losses were used for
      statistical analysis. Following regions were overrepresented: in tumors with
      stage I or II a gain of 2.98 Mb on 6p21.2-p11 and a gain of 7.4 Mb on 8q11.1
      q11.23; in tumors with grade I histology a gain of 1.1 Mb on 8q24.13, a loss of a
      large part of p arm of chromosome 3, a loss of a 1.24 Mb on 6q14.3, and a loss of
      terminal 32 Mb region of 8p23.3; in cases with affected lymph nodes a gain of
      0.75 Mb on 3q24, and a gain of 0.9 Mb on 3q26.32-q26.33; in cases with unaffected
      lymph nodes a gain of 1.1 Mb on 8q23.3, in patients not treated with surgery a
      gain of 12.2 Mb on 7q21.3-q22.3 and a gain of 0.33 Mb on 20q11.22. Conclusions:
      Our study identified several genomic regions of interest which appear to be
      associated with various clinically distinct subgroups of head and neck cancer.
      They represent a potentially important source of biomarkers useful for the
      clinical management of head and neck cancer. In particular, the PIK3CA and AGTR1
      genes could be singled out to predict the lymph node involvement.

PMID- 29371889
TI  - Cytogenetic/mutation profile of chronic lymphocytic leukemia/malignant melanoma
      collision tumors of the skin.
AB  - Background: Collision tumors are rare entities that consist of two histologically
      distinct tumor types arising in the same anatomic site. An association between
      chronic lymphocytic leukemia (CLL) and malignant melanoma (MM) has been already
      described. Up to now, they have been documented only at positive regional lymph
      nodes while we focused on collision tumor in a skin lesion. Case presentation: We
      characterized the genomic profile of a skin CLL/MM collision tumor in a patient
      with a 9-years story of CLL. Typical high-grade genomic biomarkers featured the
      CLL: the immunoglobulin heavy variable genes were unmutated; a clonal del(11q),
      involving ATM and BIRC3, was present in the peripheral blood (PB) and skin
      lesion, while a subclonal large del(13q)/D13S319-RB1 was detected only in the PB.
      Interestingly, the del(13q) clone, increased from 10% to 46% from diagnosis to
      relapse. NOTCH1, SF3B1, and TP53 were wild type. The MM lesion carried a
      BRAFV600E and a TERT promoter mutation.As the family story was consistent with a
      genetic predisposition to cancer, we performed mutational analysis of genes
      involved in familial melanoma and CLL, and of BRCA1 and BRCA2. No germinal
      mutation known to predispose to CLL, MM, or breast cancer was found.
      Interestingly, conventional cytogenetic detected a constitutional
      t(12;17)(p13;p13). Conclusions: Our data are consistent with distinct genetic
      landscape of the two tumors which were characterized by specific disease-related
      abnormalities. CLL cells carried poor prognostic imbalances, i.e. large deletions
      of the long arm of chromosomes 11 and 13, while in MM cells two functionally
      linked mutations, i.e. BRAFV600E and a TERT promoter occurred. Although, known
      germline variations predisposing to MM and/or CLL were ruled out, genetic
      counseling suggested the proband family was at high risk for MM.

PMID- 29371891
TI  - Characterization of a functional insertion sequence ISSau2 from Staphylococcus
      aureus.
AB  - Background: ISSau2 has been suggested as a member of the IS150 f subgroup in the
      IS3 family. It encodes a fusion transposase OrfAB produced by programmed - 1
      translational frameshifting with two overlapping reading frames orfA and orfB. To
      better characterize ISSau2, the binding and cleaving activities of the ISSau2
      transposase and its transposition frequency were studied. Results: The purified
      ISSau2 transposase OrfAB was a functional protein in vitro since it bound
      specifically to ISSau2 terminal inverted repeat sequences (IRs) and cleaved the
      transposon ends at the artificial mini-transposon pUC19-IRL-gfp-IRR. In addition,
      the transposition frequency of ISSau2 in vivo was approximately 1.76 +/- 0.13 *
      10- 3, based on a GFP hop-on assay. Furthermore, OrfB cleaved IRs with the
      similar catalytic activity of OrfAB, while OrfA had no catalytic activity.
      Finally, either OrfA or OrfB significantly reduced the transposition of ISSau2
      induced by OrfAB. Conclusion: We have confirmed that ISSau2 is a member of
      IS150/IS3 family. The ISSau2 transposase OrfAB could bind to and cleave the
      specific fragments containing the terminal inverted repeat sequences and induce
      the transposition, suggesting that ISSau2 is at least partially functional.
      Meanwhile, both OrfA and OrfB inhibited the transposition by ISSau2. Our results
      will help understand biological roles of ISSau2 in its host S. aureus.

PMID- 29371890
TI  - Diabetic Foot Australia guideline on footwear for people with diabetes.
AB  - Background: The aim of this paper was to create an updated Australian guideline
      on footwear for people with diabetes. Methods: We reviewed new footwear
      publications, (inter)national guidelines, and consensus expert opinion alongside
      the 2013 Australian footwear guideline to formulate updated recommendations.
      Result: We recommend health professionals managing people with diabetes should:
      (1) Advise people with diabetes to wear footwear that fits, protects and
      accommodates the shape of their feet. (2) Advise people with diabetes to always
      wear socks within their footwear, in order to reduce shear and friction. (3)
      Educate people with diabetes, their relatives and caregivers on the importance of
      wearing appropriate footwear to prevent foot ulceration. (4) Instruct people with
      diabetes at intermediate- or high-risk of foot ulceration to obtain footwear from
      an appropriately trained professional to ensure it fits, protects and
      accommodates the shape of their feet. (5) Motivate people with diabetes at
      intermediate- or high-risk of foot ulceration to wear their footwear at all
      times, both indoors and outdoors. (6) Motivate people with diabetes at
      intermediate- or high-risk of foot ulceration (or their relatives and caregivers)
      to check their footwear, each time before wearing, to ensure that there are no
      foreign objects in, or penetrating, the footwear; and check their feet, each time
      their footwear is removed, to ensure there are no signs of abnormal pressure,
      trauma or ulceration. (7) For people with a foot deformity or pre-ulcerative
      lesion, consider prescribing medical grade footwear, which may include custom
      made in-shoe orthoses or insoles. (8) For people with a healed plantar foot
      ulcer, prescribe medical grade footwear with custom-made in-shoe orthoses or
      insoles with a demonstrated plantar pressure relieving effect at high-risk areas.
      (9) Review prescribed footwear every three months to ensure it still fits
      adequately, protects, and supports the foot. (10) For people with a plantar
      diabetic foot ulcer, footwear is not specifically recommended for treatment;
      prescribe appropriate offloading devices to heal these ulcers. Conclusions: This
      guideline contains 10 key recommendations to guide health professionals in
      selecting the most appropriate footwear to meet the specific foot risk needs of
      an individual with diabetes.

PMID- 29371892
TI  - Hearing Loss in the Elderly: Is the Hearing Handicap Inventory for the Elderly -
      Screening Version Effective in Diagnosis When Compared to the Audiometric Test?
AB  - Introduction  Hearing losses inherent to the natural process of aging represent
      today a major public health issue, despite the little attention that their
      adequate care still receives. Early recognition and proper management of these
      shortcomings can significantly improve hearing, as well as the patient's general
      quality of life, reducing the overall impact of this important and prevalent
      condition of the aging process. Objective  The aim of this research was to
      evaluate the accuracy of the Hearing Handicap Inventory for the Elderly -
      Screening Version (HHIE-S) in the diagnosis of hearing loss in the elderly when
      compared with the audiometric test. Methods  Through a cross-sectional study, our
      target population was composed of 138 individuals, aged over 60 and with any
      otorhinolaryngological complaints, recruited at the Clinic of Otorhinolaryngology
      and Speech Therapy of the Faculdade de Medicina de Marilia (Famema), in the city
      of Marilia, SP, Brazil. Patients already in the process of auditory
      rehabilitation were excluded, as well as those who did not demonstrate the
      minimum level of oral understanding necessary to allow the interview. Results 
      The prevalence of hearing loss according to the questionnaire was of 76.1%, while
      audiometry showed 79.7%. We found the diagnostic accuracy of the instrument to be
      of 86.2%, with a sensitivity of 89.1% and a specificity of 75.0%, regardless of
      gender. Conclusion  Thereby, we conclude that the standardized questionnaire
      under rating is suitable for the screening of hearing loss in the elderly, given
      its high accuracy and user-friendly quality.

PMID- 29371893
TI  - Evaluation of Dizziness Handicap in Adolescents and Adults with Auditory
      Neuropathy Spectrum Disorder.
AB  - Introduction  Vestibular symptoms and damage to the vestibular branch of the
      eighth cranial nerve is reported in individuals with auditory neuropathy spectrum
      disorder (ANSD). However, the real life handicap caused by these vestibular
      problems in individuals with ANSD is not studied. Objective  The present study
      attempted to evaluate the dizziness-related handicap in adolescents and adults
      with ANSD. Method  The dizziness handicap inventory (DHI) was administered to 40
      adolescents and adults diagnosed with ANSD. The study also attempted to determine
      if there is any gender effect on DHI scores and its correlation to the reported
      onset of hearing loss. Results  The results of the study showed that adolescents
      and adults with ANSD had a moderate degree of dizziness-related handicap. The
      dizziness affected their quality of life, causing emotional problems. There was
      no gender effect, and the level of the handicap was greater in the cases in which
      the onset of the hearing loss was reported soon after the diagnosis of ANSD.
      There could be a vestibular compensation that could have resulted in a reduction
      in symptoms in individuals in whom the onset of the hearing loss was reported
      later on. Conclusion  Thus, a detailed assessment of vestibular problems and
      their impact on quality of life is essential in adolescents and adults with ANSD.
      Appropriate management strategies should be considered to resolve their
      vestibular problems and improve their quality of life.

PMID- 29371894
TI  - The Effect of the Cholesterol Levels on Noise-Induced Hearing Loss.
AB  - Introduction  Noise-induced hearing loss (NIHL), which is one of the most common
      occupational diseases among industrialized populations, is associated with
      longstanding exposure to high levels of noise. The pathogenesis of NIHL is not
      clear, but some genes and their activity at the tissue level have been
      investigated. Hypercholesterolemia, which can disturb the microcirculation, can
      be one of the underlying pathologies in hearing loss. Objective  To investigate
      the relationship between NIHL and hypercholesterolemia. Methods  The study group
      was selected among workers who had an occupational exposure of 85 dB of noise for
      at least 10 years. The audiologic assessment was recorded at seven frequencies
      (500 Hz, 1,000 Hz, 2,000 Hz, 3,000 Hz, 4,000 Hz, 6,000 Hz and 8,000 Hz). A total
      of 456 workers were included in the study and divided into two groups: the
      control group (252 patients) and the NIHL group (204 patients). After the
      audiologic measurement, blood samples were taken and investigated for blood
      cholesterol levels. According to these results, the groups were compared. Results
      Both groups were similarly distributed regarding age and occupational exposure
      time ( p  > 0.05). We could not detect any association between cholesterol levels
      and noise-induced hearing loss ( p  < 0.05). According to logistic regression
      analyses, the odds ratios are not significant for both hypercholesterolemia and
      hypertriglyceridemia ( p  > 0.05). Conclusion  Noise-induced hearing loss is
      still a common occupational problem that can be prevented by hearing conservation
      programs and occupational health and safety training. Still, we know little about
      the relationship between NIHL and hypercholesterolemia. According to our
      findings, we cannot detect any relationship. Controlled studies and studies with
      human individuals can be made possible in the future with diagnostic innovations
      in tissue imaging and tissue microcircular sampling.

PMID- 29371895
TI  - Computerized Auditory Training in Students: Electrophysiological and Subjective
      Analysis of Therapeutic Effectiveness.
AB  - Introduction  Computerized auditory training (CAT) has been building a good
      reputation in the stimulation of auditory abilities in cases of auditory
      processing disorder (APD). Objective  To measure the effects of CAT in students
      with APD, with typical or atypical phonological acquisition, through
      electrophysiological and subjective measures, correlating them pre- and post
      therapy. Methods  The sample for this study includes14 children with APD,
      subdivided into children with APD and typical phonological acquisition (G1), and
      children with APD and atypical phonological acquisition (G2). Phonological
      evaluation of children (PEC), long latency auditory evoked potential (LLAEP) and
      scale of auditory behaviors (SAB) were conducted to help with the composition of
      the groups and with the therapeutic intervention. The therapeutic intervention
      was performed using the software Escuta Ativa (CTS Informatica, Pato Branco,
      Brazil) in 12 sessions of 30 minutes, twice a week. For data analysis, the
      appropriate statistical tests were used. Results  A decrease in the latency of
      negative wave N2 and the positive wave P3 in the left ear in G1, and a decrease
      of P2 in the right ear in G2 were observed. In the analysis comparing the pre-
      and post-CAT groups, there was a significant difference in P1 latency in the left
      ear and P2 latency in the right ear, pre-intervention. Furthermore, eight
      children had an absence of the P3 wave, pre-CAT, but after the intervention, all
      of them presented the P3 wave. There were changes in the SAB score pre- and post
      CAT in both groups. The presence of correlation between the scale and some LLAEP
      components was observed. Conclusion  The CAT produced an electrophysiological
      modification, which became evident in the effects of the effects of neural
      plasticity after CAT. The SAB proved to be useful in measuring the therapeutic
      effects of the intervention. Moreover, there were behavioral changes in the SAB
      (higher scores) and correlation with LLAEP.

PMID- 29371896
TI  - The Effects of Prognostic Factors in Idiopathic Sudden Hearing Loss.
AB  - Introduction  Sudden hearing loss is one of the otologic emergencies. The
      treatment of this disease is affected negatively by some prognostic factors.
      Objective  In this study, the effects of early treatment initiation in patients
      with idiopathic sudden hearing loss and of prognostic factors in early treated
      patients were investigated. Methods  Out of the 216 patients admitted between
      September 2007 and September 2015, 154 were identified as having idiopathic
      sudden hearing loss; they were followed-up for a mean time of 7.4 months, and
      evaluated retrospectively. The effects of several parameters on the success of
      the treatment were statistically evaluated, such as the time the treatment was
      initiated, being of the female gender, the severity of the hearing loss, having
      descending type audiogram patterns, being older than 60 years old, and the co
      presence of vertigo. Results  Success rates were found to be significantly higher
      in idiopathic hearing loss patients that were admitted within the first week ( p 
      < 0.05) of the onset of the hearing loss. However, the outcomes were found to be
      similar when patients admitted within the first 3 days and 4-7 days after the
      occurrence of the hearing loss were compared ( p  > 0.05). Parameters such as
      female gender, severe hearing loss, descending type audiogram, being older than
      60 years old, and co-presence of vertigo didn't reveal statistically significant
      effects on the outcome ( p >0.05). Conclusion  The aforementioned prognostic
      factors, which are well-known in the literature, did not have significant effects
      when the idiopathic sudden hearing loss treatment was initiated within the first
      7 days of the onset of the hearing loss.

PMID- 29371897
TI  - Does Body Mass Index Interfere in the Formation of Speech Formants?
AB  - Introduction  Studies in the fields of voice and speech have increasingly focused
      on the vocal tract and the importance of its structural integrity, and changes in
      the anatomy and configuration of the vocal tract determine the variations in
      phonatory and acoustic measurements, especially in the formation of the formants
      (Fs). Recent studies have revealed the functional consequences arising from being
      overweight and having an accumulation of fat in the pharyngeal region, including
      obstructive sleep apnea syndrome (OSAS) and impacts on the voice. Objectives  To
      assess the relationship between body mass index (BMI) and analysis of the speech.
      Methods  This study was approved by the Ethics Committee of the Universidade
      Federal de Sao Paulo (no. 288,430). The cohort consisted of 124 individuals aged
      between 18 and 45 with full permanent dentition and selected randomly. The
      participants underwent a brief medical history taking, BMI assessments and
      recording emissions of the sustained vowels /a/, /epsilon/, /i/, and /u/ by
      acoustic program PRAAT (v. 5.3.85, Boersma and Weenink, Amsterdam, Netherlands).
      Recordings were taken using a unidirectional microphone headset (model Karsect HT
      9, Guangdong, China), with a condenser connected to an external sound card (USB
      SA 2.0, model Andrea, PureAudioTM, Pleasant Grove, UT, USA), to reduce noise.
      Results  There was a significant correlation between BMI and formant 3 (F3) vowel
      /a/; however, there was a low degree of correlation intensity. Conclusions  We
      did not observe a correlation between the BMI and the speech formants, but we
      believe there is a trend in this correlation that leads to changes in speech
      patterns with increases in BMI.

PMID- 29371898
TI  - Microbiology of Tracheal Secretions: What to Expect with Children and Adolescents
      with Tracheostomies.
AB  - Introduction  People with tracheostomies exhibit a higher risk of colonization of
      the lower respiratory tract, acute tracheitis and pneumonia. Despite this, the
      culture of tracheal secretions is not a routine in most hospitals, and sometimes
      empiric therapy is based on personal experience, which is not an ideal situation.
      Objective  To recognize the pathogens present in the tracheal secretions
      collected from people up to 18 years old with tracheostomies. Methods 
      Prospective evaluation of patients under the age of 18 of a tertiary care
      hospital. A standardized questionnaire was completed, and tracheal secretion
      aspirates were sent for microbiological cultures and antibiograms. Results 
      Twenty patients under 18 years of age were evaluated, 65% of whom were male. The
      microbiological culture was positive in 90% of the patients, and the most common
      microorganisms found were Pseudomonas aeruginosa (55.5%) and Staphylococcus
      aureus (27.7%). Discussion  Tracheostomized children and adolescents have
      respiratory tracts colonized by pathogens, the most common of which is
      Pseudomonas aeruginosa . These patients must undergo tracheal secretion cultures,
      whether they present symptoms or not, to determine if there is a correlation
      between the colonization and the infections. This finding could guide the
      adequate treatment, avoiding the inappropriate use of antibiotics and indicating
      the better therapy in cases of laryngeal reconstruction. Conclusion  In this
      sample, the culture of tracheal secretions was mainly positive, and the most
      common agent was P. aeruginosa . We suggest the routine access to Brazilian
      children and adolescents tracheal secretion cultures, which could help to make a
      profile of these children and guide the use of antibiotics.

PMID- 29371899
TI  - Adenotonsillar Hypertrophy in Pre-School Children with Sickle Cell Disease and
      Diagnostic Accuracy of the Sleep Disturbance Scale for Children.
AB  - Introduction  Adenotonsillar hypertrophy is more common in children with sickle
      cell disease, and can lead to sleep-disordered breathing. Objectives  To
      determine the frequency of adenotonsillar hypertrophy in pre-school children with
      sickle cell disease and assess the diagnostic accuracy of the sleep-disordered
      breathing subscale in the Sleep Disturbance Scale for Children. Method 
      Observational study with a group of 48 children with sickle cell disease and a
      control group of 35 children without the disease. The children underwent
      oropharingoscopy and video nasal endoscopy. The parents and/or guardians answered
      the questions of the subscale. Results  Adenotonsillar hypertrophy was observed
      in 25% of the children in the study group, and in 20% of the children in the
      control group, with no statistical difference between the groups. The subscale
      score ranged from 3 to 11 in both groups. There was a statistical significance in
      the study group. The average was 4.79 (standard deviation [SD] +/- 2.50), with
      4.19 (SD +/- 1.72) among the children without adenotonsillar hypertrophy, and 6.5
      (SD +/- 3.40) among the children with adenotonsillar hypertrophy. There was also
      a statistical significance in the control group. The average was 5.23 (SD +/-
      2.81), with 4.44 (SD +/- 2.2) among the children without adenotonsillar
      hypertrophy, and 7.87 (SD +/- 2.89) among the children with adenotonsillar
      hypertrophy. Conclusion  Adenotonsillar hypertrophy was not associated with
      sickle cell disease in pre-school children. The subscale of sleep-disordered
      breathing in the Sleep Disturbance Scale for Children was a useful tool for the
      diagnostic suspicion of adenotonsillar hypertrophy in children in this age group.

PMID- 29371900
TI  - Development and Evaluation of a Blog about Cleft Lip and Cleft Palate and
      Hearing.
AB  - Introduction  Cleft lip and cleft palate can result in impairments in
      communication, specifically in hearing, making the use of technological resources
      such as blogs a fundamental guideline for health professionals. Objective  The
      aim of this study was to prepare and analyze the access to a blog about cleft lip
      and cleft palate and hearing as a pedagogical tool for health professionals.
      Methods  The first stage for the development of the blog was the selection of the
      content that would be addressed and the respective illustrations. The second
      stage was making the blog available through the WordPress platform, and the third
      stage included the evaluation of the blog, of the access to the WordPress
      statistical features, and of the quality of the blog through the Emory
      questionnaire, which was answered by 75 professionals. Results  The blog, titled
      "Fissure and Hearing", was developed with the architecture of a digital
      information environment containing a system of organization, navigation, labeling
      and search (first stage). The address hosting the blog was:
      http://fissuraeaudicao.wordpress.com (second stage). The result of the third
      stage included 56,269 views of the blog from different countries, and Brazil was
      the country with the highest viewing. Regarding the assessment by the Emory
      questionnaire, we found that for most of the major issues, the percentages
      obtained were or equal to 90%, while the analysis of the scales, navigation and
      structure presented the lowest scores. Conclusion  The blog was developed and
      enabled greater access to information available on the web about cleft lip and
      cleft palate and hearing.

PMID- 29371901
TI  - Modified In-Office Maxillary Balloon Sinus Dilation for Post-Procedure Sinus
      Monitoring and Access.
AB  - Introduction  As experience grows with in-office balloon sinus dilation (BSD)
      procedures, technique modifications will evolve to meet specific needs. The major
      disadvantage with the maxillary BSD procedure is that the intact uncinate process
      prevents visualization of and instrument access into the maxillary sinus both
      intraoperatively and postoperatively. Combining a partial or complete uncinectomy
      procedure with maxillary BSD could be beneficial in selected patients with
      certain maxillary sinus problems. Objective  The primary objective of this study
      was to see if, in selected patients, combining an uncinectomy and maxillary sinus
      BSD together allowed visualization of and access to the maxillary sinus cavity at
      the time of the procedure and at follow-up visits. Method  A chart review was
      completed for BSD cases performed from 2013 through mid-2015 identifying patients
      who underwent partial or complete uncinectomy with in-office maxillary sinus BSD.
      A total of 14 patients were identified, with 26 sinuses treated. The data
      collected included: difficulty or problems in performing an uncinectomy with the
      maxillary sinus BSD; visualization and access to the maxillary sinus cavity both
      intraoperatively and at follow-up visits; and occurrence of complications or late
      adverse sequelae. All patients completed a minimum 6-month follow-up. Results 
      Combined uncinectomy and maxillary sinus BSD procedures were easily completed for
      all patients without complications, and no late adverse sequelae were
      encountered. The maxillary sinuses could be visualized and accessed, if needed,
      intraoperatively and at all follow-up visits. Conclusions  In selected subsets of
      maxillary sinus conditions this procedure modification can provide significant
      benefits. A case is presented for illustration.

PMID- 29371902
TI  - Tomographical Findings in Adult Patients Undergoing Endoscopic Sinus Surgery
      Revision.
AB  - Introduction  Many patients undergoing functional endoscopic sinus surgery still
      have an uncontrolled clinical disease in the late post-operative period. Up to
      11.4% of the patients will require a revision surgery. Findings such as the
      residual uncinated process and the lateralization of the middle turbinate were
      considered by some studies as being responsible for failure in the primary
      surgery. Objectives  To describe the tomographical findings in adult patients
      undergoing revision endoscopic sinus surgery, the profile of those patients, and
      verify the mucosal thickening level of the paranasal sinus. Methods  Data were
      collected from medical records and computed tomography reports of 28 patients
      undergoing revision sinus surgery on a private service in the city of Blumenau
      between 2007 and 2014. The score of Lund-Mackay was used to verify the mucosal
      thickening level. Results  Among the 28 patients, 23 were reoperated once, 3 were
      reoperated twice, and 2 were reoperated 3 times. The most relevant findings were
      mucosal thickening of the maxillary sinus (89.28%), deviated septum (75%),
      thickening of the ethmoid (50%) and sphenoidal sinuses (39.28%), and
      pneumatization of the middle turbinate (39.28%). The average obtained in the Lund
      Mackay score was 5.71, with most patients classified in the lower range of
      punctuation. Conclusion  The analysis of the computed tomography scans showed
      persistent structures that may be responsible for the failure of the primary
      surgery. Computed tomography is a useful tool to plan the surgery and quantify
      the post-operative success.

PMID- 29371903
TI  - Tobacco Influence on Taste and Smell: Systematic Review of the Literature.
AB  - Introduction  In Brazil, estimates show that 14.7% of the adult population
      smokes, and changes in smell and taste arising from tobacco consumption are
      largely present in this population, which is an aggravating factor to these
      dysfunctions. Objectives  The objective of this study is to systematically review
      the findings in the literature about the influence of smoking on smell and taste.
      Data Synthesis  Our research covered articles published from January 1980 to
      August 2014 in the following databases: MEDLINE (accessed through PubMed),
      LILACS, Cochrane Library, and SciELO. We conducted separate lines of research:
      one concerning smell and the other, taste. We analyzed all the articles that
      presented randomized controlled studies involving the relation between smoking
      and smell and taste. Articles that presented unclear methodologies and those
      whose main results did not target the smell or taste of the subjects were
      excluded. Titles and abstracts of the articles identified by the research
      strategy were evaluated by researchers. We included four studies, two of which
      were exclusively about smell: the first noted the relation between the perception
      of puff strength and nicotine content; the second did not find any differences in
      the thresholds and discriminative capacity between smokers and nonsmokers. One
      article considered only taste and supports the relation between smoking and
      flavor, another considered both sensory modalities and observes positive results
      toward the relation immediately after smoking cessation. Conclusion  Three of the
      four studies presented positive results for the researched variables.

PMID- 29371904
TI  - Computer-Based Auditory Training Programs for Children with Hearing Impairment -
      A Scoping Review.
AB  - Introduction  Communication breakdown, a consequence of hearing impairment (HI),
      is being fought by fitting amplification devices and providing auditory training
      since the inception of audiology. The advances in both audiology and
      rehabilitation programs have led to the advent of computer-based auditory
      training programs (CBATPs). Objective  To review the existing literature
      documenting the evidence-based CBATPs for children with HIs. Since there was only
      one such article, we also chose to review the commercially available CBATPs for
      children with HI. The strengths and weaknesses of the existing literature were
      reviewed in order to improve further researches. Data Synthesis  Google Scholar
      and PubMed databases were searched using various combinations of keywords. The
      participant, intervention, control, outcome and study design (PICOS) criteria
      were used for the inclusion of articles. Out of 124 article abstracts reviewed, 5
      studies were shortlisted for detailed reading. One among them satisfied all the
      criteria, and was taken for review. The commercially available programs were
      chosen based on an extensive search in Google. The reviewed article was well
      structured, with appropriate outcomes. The commercially available programs cover
      many aspects of the auditory training through a wide range of stimuli and
      activities. Conclusions  There is a dire need for extensive research to be
      performed in the field of CBATPs to establish their efficacy, also to establish
      them as evidence-based practices.

PMID- 29371905
TI  - Clinical Features and Treatment of Fibrous Histiocytomas of the Tongue: A
      Systematic Review.
AB  - Introduction  Benign fibrous histiocytomas are common lesions of the skin that
      rarely affect the tongue. Such cases are available in the literature exclusively
      as case reports. Similarly, malignant fibrous histiocytoma, now classified as
      undifferentiated pleomorphic sarcoma, is exceedingly rare in the tongue and not
      fully understood. Objectives  This study systematically reviews the available
      literature discussing the clinical and pathological features of malignant and
      benign fibrous histiocytomas. Data Synthesis  A total of 20 cases were included
      in this review. Patient-level data were extracted from cases to include clinical
      presentation, workup, treatment, and outcome. Conclusion  Benign fibrous
      histiocytomas are consistent in clinical and histopathologic presentation.
      Surgical treatment provides excellent outcome, with no recurrence in all excised
      cases. Malignant tumors have a more aggressive clinical and pathological
      presentation. Surgical treatment with possible adjuvant radiotherapy resulted in
      recurrence in 40% of cases (follow-up of 24 months), and death due to disease in
      47% of patients (follow-up of 19 months).

PMID- 29371907
TI  - Nanostructure design for drastic reduction of thermal conductivity while
      preserving high electrical conductivity.
AB  - The design and fabrication of nanostructured materials to control both thermal
      and electrical properties are demonstrated for high-performance thermoelectric
      conversion. We have focused on silicon (Si) because it is an environmentally
      friendly and ubiquitous element. High bulk thermal conductivity of Si limits its
      potential as a thermoelectric material. The thermal conductivity of Si has been
      reduced by introducing grains, or wires, yet a further reduction is required
      while retaining a high electrical conductivity. We have designed two different
      nanostructures for this purpose. One structure is connected Si nanodots (NDs)
      with the same crystal orientation. The phonons scattering at the interfaces of
      these NDs occurred and it depended on the ND size. As a result of phonon
      scattering, the thermal conductivity of this nanostructured material was
      below/close to the amorphous limit. The other structure is Si films containing
      epitaxially grown Ge NDs. The Si layer imparted high electrical conductivity,
      while the Ge NDs served as phonon scattering bodies reducing thermal conductivity
      drastically. This work gives a methodology for the independent control of
      electron and phonon transport using nanostructured materials. This can bring the
      realization of thermoelectric Si-based materials that are compatible with large
      scale integrated circuit processing technologies.

PMID- 29371906
TI  - Profile of epigenetic mechanisms in lung tumors of patients with underlying
      chronic respiratory conditions.
AB  - Background: Chronic lung diseases such as chronic obstructive pulmonary disease
      (COPD) and epigenetic events underlie lung cancer (LC) development. The study
      objective was that lung tumor expression levels of specific microRNAs and their
      downstream biomarkers may be differentially regulated in patients with and
      without COPD. Methods: In lung specimens (tumor and non-tumor), microRNAs known
      to be involved in lung tumorigenesis (miR-21, miR-200b, miR-126, miR-451, miR
      210, miR-let7c, miR-30a-30p, miR-155 and miR-let7a, qRT-PCR), DNA methylation,
      and downstream biomarkers were determined (qRT-PCR and immunoblotting) in 40
      patients with LC (prospective study, subdivided into LC-COPD and LC, N =
      20/group). Results: Expression of miR-21, miR-200b, miR-210, and miR-let7c and
      DNA methylation were greater in lung tumor specimens of LC-COPD than of LC
      patients. Expression of downstream markers PTEN, MARCKs, TPM-1, PDCD4, SPRY-2,
      ETS-1, ZEB-2, FGFRL-1, EFNA-3, and k-RAS together with P53 were selectively
      downregulated in tumor samples of LC-COPD patients. In these patients, tumor
      expression of miR-126 and miR-451 and that of the biomarkers PTEN, MARCKs, FGFRL
      1, SNAIL-1, P63, and k-RAS were reduced. Conclusions: Biomarkers of mechanisms
      involved in tumor growth, angiogenesis, migration, and apoptosis were
      differentially expressed in tumors of patients with underlying respiratory
      disease. These findings shed light into the underlying biology of the reported
      greater risk to develop LC seen in patients with chronic respiratory conditions.
      The presence of an underlying respiratory disease should be identified in all
      patients with LC as the differential biological profile may help determine tumor
      progression and the therapeutic response. Additionally, epigenetic events offer a
      niche for pharmacological therapeutic targets.

PMID- 29371908
TI  - Genetic variants of prospectively demonstrated phenocopies in BRCA1/2 kindreds.
AB  - Background: In kindreds carrying path_BRCA1/2 variants, some women in these
      families will develop cancer despite testing negative for the family's pathogenic
      variant. These families may have additional genetic variants, which not only may
      increase the susceptibility of the families' path_BRCA1/2, but also be capable of
      causing cancer in the absence of the path_BRCA1/2 variants. We aimed to identify
      novel genetic variants in prospectively detected breast cancer (BC) or
      gynecological cancer cases tested negative for their families' pathogenic BRCA1/2
      variant (path_BRCA1 or path_BRCA2). Methods: Women with BC or gynecological
      cancer who had tested negative for path_BRCA1 or path_BRCA2 variants were
      included. Forty-four cancer susceptibility genes were screened for genetic
      variation through a targeted amplicon-based sequencing assay. Protein- and RNA
      splicing-dedicated in silico analyses were performed for all variants of unknown
      significance (VUS). Variants predicted as the ones most likely affecting pre-mRNA
      splicing were experimentally analyzed in a minigene assay. Results: We identified
      48 women who were tested negative for their family's path_BRCA1 (n = 13) or
      path_BRCA2 (n = 35) variants. Pathogenic variants in the ATM, BRCA2, MSH6 and
      MUTYH genes were found in 10% (5/48) of the cases, of whom 15% (2/13) were from
      path_BRCA1 and 9% (3/35) from path_BRCA2 families. Out of the 26 unique VUS, 3
      (12%) were predicted to affect RNA splicing (APC c.721G > A, MAP3K1 c.764A > G
      and MSH2 c.815C > T). However, by using a minigene, assay we here show that APC
      c.721G > A does not cause a splicing defect, similarly to what has been recently
      reported for the MAP3K1 c.764A > G. The MSH2 c.815C > T was previously described
      as causing partial exon skipping and it was identified in this work together with
      the path_BRCA2 c.9382C > T (p.R3128X). Conclusion: All women in breast or
      breast/ovarian cancer kindreds would benefit from being offered genetic testing
      irrespective of which causative genetic variants have been demonstrated in their
      relatives.

PMID- 29371909
TI  - Persistence and Fadeout in the Impacts of Child and Adolescent Interventions.
AB  - Many interventions targeting cognitive skills or socioemotional skills and
      behaviors demonstrate initially promising but then quickly disappearing impacts.
      Our paper seeks to identify the key features of interventions, as well as the
      characteristics and environments of the children and adolescents who participate
      in them, that can be expected to sustain persistently beneficial program impacts.
      We describe three such processes: skill-building, foot-in-the-door and sustaining
      environments. We argue that skill-building interventions should target "trifecta"
      skills - ones that are malleable, fundamental, and would not have developed
      eventually in the absence of the intervention. Successful foot-in-the-door
      interventions equip a child with the right skills or capacities at the right time
      to avoid imminent risks (e.g., grade failure or teen drinking) or seize emerging
      opportunities (e.g., entry into honors classes). The sustaining environments
      perspective views high quality of environments subsequent to the completion of
      the intervention as crucial for sustaining early skill gains. These three
      perspectives generate both complementary and competing hypotheses regarding the
      nature, timing and targeting of interventions that generate enduring impacts.

PMID- 29371910
TI  - Draft genome sequence of Streptomyces hyaluromycini MB-PO13T, a hyaluromycin
      producer.
AB  - Streptomyces hyaluromycini MB-PO13T (=NBRC 110483T = DSM 100105T) is type strain
      of the species, which produces a hyaluronidase inhibitor, hyaluromycin. Here, we
      report the draft genome sequence of this strain together with features of the
      organism and generation, annotation and analysis of the genome sequence. The 11.5
      Mb genome of Streptomyces hyaluromycini MB-PO13T encoded 10,098 putative ORFs, of
      which 5317 were assigned with COG categories. The genome harbored at least six
      type I PKS clusters, three type II PKS gene clusters, two type III PKS gene
      clusters, six NRPS gene clusters, and one hybrid PKS/NRPS gene cluster. The type
      II PKS gene cluster including 2-amino-3-hydroxycyclopent-2-enone synthetic genes
      was identified to be responsible for hyaluromycin synthesis. We propose the
      biosynthetic pathway based on bioinformatic analysis.

PMID- 29371911
TI  - TLR signaling inhibitor, phenylmethimazole, in combination with tamoxifen
      inhibits human breast cancer cell viability and migration.
AB  - Heightened co-expression and dysregulated signaling associated with Toll-like
      receptor 3 (TLR3) and Wnt5a is an integral component of solid tumors and
      hematological malignancies. Our previous findings in pancreatic cancer and
      melanoma suggest that inhibition of these pathways by a TLR3 signaling inhibitor,
      phenylmethimazole (C10), results in significantly decreased IL-6 levels, STAT3
      phosphorylation, minimal cancer cell migration and reduced cancer cell growth in
      vitro and in vivo. In this study, we extended our earlier observations by
      performing studies in human breast cancer cells. We found that human MCF-7 breast
      cancer cells express high basal levels of TLR3 and Wnt5a RNA. C10 treatment
      resulted in significantly decreased TLR3 and Wnt5a expression levels. This
      functionally translated into significantly reduced IL-6 levels and STAT3
      phosphorylation in vitro. In addition, the inhibition of this signaling cascade
      by C10 further resulted in decreased cell viability and migration of MCF-7 cells.
      Strikingly, the combination of C10 and tamoxifen, the standard of care therapy
      for breast cancer, further decrease cancer cell growth better than either agent
      alone. These data support the novel finding that inhibition of TLR3 signaling in
      combination with tamoxifen, may increase the effectiveness of current treatments
      of breast cancer.

PMID- 29371912
TI  - The regulation of NLRP3 inflammasome expression during the development of cardiac
      contractile dysfunction in chronic kidney disease.
AB  - Chronic inflammation plays a crucial role in the long-term complications in
      patients with chronic kidney disease (CKD). This study aimed to assess the role
      of NLR pyrin domain-containing protein (NLRP3) inflammasome in cardiac
      contractile dysfunctions in CKD. The cardiac contractile function was evaluated
      and the expression of NLRP3 inflammasome and related cytokines in the heart was
      assessed in a murine sham-operated and 5/6 nephrectomy CKD model in vivo. In
      vitro, H9c2 cells were treated with uremic toxin indoxyl sulfate (IS), with or
      without NLRP3 inflammasome inhibition, which was achieved by using small
      interfering RNA (siRNA)-mediated knockdown of the NLRP3 gene. Moreover, the
      activation of nuclear factor kappaB (NF-kappaB) signaling and apoptosis marker
      levels were assessed in the IS-treated H9c2 cells. The results demonstrated that
      CKD can lead to the development of cardiac contractile dysfunction in vivo
      associated with the upregulation of NLRP3 inflammasome, IL-1beta, IL-18, and
      contribute to the myocardial apoptosis. In vitro experiments showed the
      upregulation of inflammasome, IL-1beta, and IL-18 levels, and cell apoptosis in
      the IS-treated H9c2 cells through the activation of NF-kappaB signaling pathway.
      The transfection of cells with si-NLRP3 was shown to alleviate IL-1beta, IL-18,
      and cell apoptosis. Moreover, decreased cell viability induced by IS was shown to
      be attenuated by IL-1beta or IL-18-neutralizing antibody. In summary, CKD can
      result in the development of cardiac contractile dysfunction associated with the
      upregulation of NLRP3 inflammasome/IL-1beta/IL-18 axis induced by the uremic
      toxins.

PMID- 29371913
TI  - Evaluation of efficacy and safety for bevacizumab in treating malignant pleural
      effusions caused by lung cancer through intrapleural injection.
AB  - Some clinical investigations have assessed the efficacy and safety of bevacizumab
      combined with platinum anti-cancer drugs versus platinum drugs alone in treating
      malignant pleural effusion (MPE) caused by lung cancer through intrapleural
      injection. This report is a meta-analysis of independent research conclusions.
      Eleven controlled trials with 769 MPE patients were included in this report.
      Pooled odds ratios and standardized mean difference with 95% confidence intervals
      were estimated using the fixed or random effects model of meta-analysis. For
      treating MPE through intrapleural injection, bevacizumab combined with platinum
      chemotherapy drugs increased the overall response rate (p = 0.003), decreased the
      incidence of chest pain (p < 0.001) and relieved the dyspnea of patients with MPE
      (p = 0.002), as compared with platinum chemotherapy drugs alone. In addition,
      intrapleural injection of bevacizumab participation decreased the expression of
      vascular endothelial growth factor in MPE (p < 0.001). The main adverse effects
      of two groups were myelotoxicity, hypertension, digestive reaction and damage of
      liver and kidney. However, the presence of bevacizumab did not show an extra
      influence on the incidence of adverse effects (p > 0.05). In summary, bevacizumab
      combined with platinum chemotherapy drugs for treating MPE caused by lung cancer
      through intrapleural injection has a better benefit of overall response rate and
      quality of life. And, the participation of bevacizumab did not increase adverse
      effects.

PMID- 29371914
TI  - MAEL contributes to gastric cancer progression by promoting ILKAP degradation.
AB  - The cancer-testis gene MAEL is involved in the development and progression of
      bladder, liver and colorectal cancers. However, its role in other cancers is
      unclear. By systematically analyzing transcriptomics and genomics data from
      various cancer databases, we identified that the MAEL gene is aberrantly elevated
      in gastric cancer (GC) tissues and that its expression is strongly negatively
      correlated with DNA methylation (Pearson's correlation coefficient = -0.675).
      Survival analysis revealed that MAEL expression may serve as a prognostic marker
      for GC patients (overall survival: hazard ratio [HR] = 1.54, p = 1.2E-4; first
      progression: HR = 1.51, p = 8.7E-4). In vitro and in vivo experiments
      demonstrated that silencing MAEL expression in the GC cell lines HGC-27 and AGS
      inhibits proliferation, colony formation, migration, invasion and growth of
      xenograft tumors, whereas MAEL overexpression exerts the opposite effects in the
      normal gastric cell line GES-1. Mechanistically, MAEL promotes the lysosome
      dependent degradation of the protein phosphatase ILKAP, leading to increased
      phosphorylation of its substrates (p38, CHK1 and RSK2). Moreover, adenovirus
      mediated ILKAP overexpression reversed the oncogenic effects of MAEL in vitro and
      in vivo. Taken together, these results indicate that MAEL exerts its oncogenic
      function by promoting ILKAP degradation in the GC.

PMID- 29371915
TI  - Expansion of tumor-infiltrating lymphocytes and their potential for application
      as adoptive cell transfer therapy in human breast cancer.
AB  - Adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes
      (TILs) has been successful in treating a considerable proportion of patients with
      metastatic melanoma. In addition, some patients with several other solid tumors
      were recently reported to have benefited clinically from such ACT. However, it
      remains unclear whether ACT using TILs is broadly applicable in breast cancer,
      the most common cancer in women. In this study, the utility of TILs as an ACT
      source in breast cancers was explored by deriving TILs from a large number of
      breast cancer samples and assessing their biological potentials. We successfully
      expanded TILs ex vivo under a standard TIL culture condition from over 100 breast
      cancer samples, including all breast cancer subtypes. We also found that the
      information about the percentage of TIL and presence of tertiary lymphoid
      structure in the tumor tissues could be useful for estimating the number of
      obtainable TILs after ex vivo culture. The ex vivo expanded TILs contained a
      considerable level of central memory phenotype T cells (about 20%), and a large
      proportion of TIL samples were reactive to autologous tumor cells in vitro.
      Furthermore, the in vitro tumor-reactive autologous TILs could also function in
      vivo in a xenograft mouse model implanted with the primary tumor tissue.
      Collectively, these results strongly indicate that ACT using ex vivo expanded
      autologous TILs is a feasible option in treating patients with breast cancer.

PMID- 29371916
TI  - The IL-17B-IL-17 receptor B pathway promotes resistance to paclitaxel in breast
      tumors through activation of the ERK1/2 pathway.
AB  - Interleukin 17B (IL-17B) is a pro-inflammatory cytokine that belongs to the IL-17
      cytokines family and binds to IL-17 receptor B (IL-17RB). Here we found that high
      expression of IL-17B and IL-17RB is associated with poor prognosis in patients
      with breast cancer and that IL-17B expression upregulation is specifically
      associated with poorer survival in patients with basal-like breast cancer. We
      thus focused on IL-17B role in breast cancer by using luminal and triple negative
      (TN)/basal-like tumor cell lines. We found that IL-17B induces resistance to
      conventional chemotherapeutic agents. In vivo, IL-17B induced resistance to
      paclitaxel and treatment with an anti-IL-17RB neutralizing antibody completely
      restored breast tumor chemosensitivity, leading to tumor shrinkage. We next
      focused on the signaling pathways activated in human breast cancer cell lines
      upon incubation with IL-17B. We observed that IL-17B induces ERK1/2 pathway
      activation, leading to upregulation of anti-apoptotic proteins of the BCL-2
      family. IL-17B-induced chemoresistance was completely abolished by incubation
      with PD98059, an inhibitor of the MAPK/ERK pathway, indicating that the ERK
      pathway plays a crucial role. Altogether our results emphasize the role of the IL
      17B/IL-17RB signaling pathway in breast tumors and identify IL-17B and its
      receptor as attractive therapeutic targets for potentiating breast cancer
      chemotherapy.

PMID- 29371918
TI  - Long-term administration of tacrolimus and everolimus prevents high cholesterol
      high fructose-induced steatosis in C57BL/6J mice by inhibiting de-novo
      lipogenesis.
AB  - Aim: To investigate the effects of tacrolimus (TC) and everolimus (EV) on non
      alcoholic steatohepatitis (NASH) induced by high fat, high cholesterol and
      fructose (fast food) diet in C57BL/6J mice. Materials and Methods: C57BL/6J mice
      were divided into four groups (n=8). 1) Standard Chow (SC); 2) Fast food (FF)
      diet; 3) FF + Tacrolimus (TC, 1mg/kg) and; 4) FF + Everolimus (EV, 1mg/kg) and
      treated for 16 weeks. Serum and tissue samples were analyzed for evidence of
      inflammation, fibrosis, lipogenesis, and apoptosis. Results: TC and EV treatments
      significantly reduced the hepatic lipid accumulation, improved liver-body weight
      ratio, blood biochemistry, and insulin resistance in mice fed with FF diet.
      However, inflammation, enlarged portal tracts, and fibrosis were pronounced in EV
      treated group. The lipogenic parameters, Peroxisome proliferator-activated
      receptor gamma (PPAR-gamma), Sterol regulatory element-binding protein 1(SREBP
      1), mammalian target of rapamycin (m-TOR), Stearoyl-CoA desaturase-1 (SCD-1) and
      fatty acid translocase (CD36) were significantly down-regulated in livers of TC
      and EV treated groups as compared to FF group. TC improved Bcl2/Bax ratio,
      decreased apoptosis, CYP2E1 protein expression and liver fibrosis levels,
      however, EV offered no such protection. Further, in an In-vitro model of
      lipotoxicity using the mouse hepatocyte (AML-12) cell line, treatment with TC and
      EV significantly reduced lipid accumulation and lipogenic and apoptotic markers
      induced with palmitic acid. Conclusion: In FF diet induced model of NASH, both TC
      and EV inhibited hepatic lipid accumulation and improved metabolic parameters
      such as insulin resistance and dyslipidemia. However, mice administered with EV
      exhibited inflammatory and fibrotic responses despite reduced hepatic steatosis.

PMID- 29371919
TI  - Sensitizing Ewing sarcoma to chemo- and radiotherapy by inhibition of the DNA
      repair enzymes DNA protein kinase (DNA-PK) and poly-ADP-ribose polymerase (PARP)
      1/2.
AB  - Background: DNA-PK and PARP inhibitors sensitize cancer cells to chemo- and
      radiotherapy. ETS transcription factors (EWS-FLI1) have been described as
      biomarkers for PARP-inhibitor sensitivity. Sensitivity to single agent PARP
      inhibitors has so far been limited to homologous recombination repair (HRR)
      deficient tumors, exploiting synthetic lethality. Results: In clonogenic assays,
      single agent rucaparib LD50 values for continuously exposed cells were similar to
      those observed in HRR-defective cells (CAPAN-1 cell line, BRCA2 defective);
      however, both ES cell lines (TC-71, CADO-ES1) had functional HRR. In vivo
      rucaparib administration (10 mg/kg daily) showed no responses. In clonogenic
      assays, rucaparib enhanced temozolomide, camptothecin and radiation cytotoxicity,
      which was most profound for temozolomide (15-29 fold enhancement). NU7441
      increased the cytotoxicity of etoposide, doxorubicin and radiation. Materials and
      Methods: We assessed PARP1/2 (rucaparib) and DNA-PK (NU7441) inhibitors in Ewing
      sarcoma (ES) cell lines by performing growth inhibition and clonogenic assays.
      HRR was measured by RAD51 focus formation. Single agent rucaparib was assessed in
      an in vivo orthotopic model. Conclusions: Single agent rucaparib ES sensitivity
      in vitro was not replicated in vivo. DNA-PK and PARP inhibitors are good chemo
      /radiosensitizers in ES. The future of these inhibitors lies in their combination
      with chemo-/radiotherapy, which needs to be evaluated in clinical trials.

PMID- 29371920
TI  - Hypermethylation of BEND5 contributes to cell proliferation and is a prognostic
      marker of colorectal cancer.
AB  - Aberrant hypermethylation of CpG islands in tumor suppressor genes (TSGs)
      contributes to colorectal tumorigenesis. To identify new colorectal cancer (CRC)
      screening marker, we investigated DNA methylation alterations in novel TSGs.
      Using HumanMethylation450 BeadChip arrays, CpG regions in BEND5 were the most
      highly methylated among all genomic regions in 26 colorectal tumors compared to
      paired non-neoplastic tissues from a Taiwan cohort. Therefore, BEND5 was selected
      for further analysis. Quantitative methylation-specific real-time PCR revealed
      that 86.7% (117/135) of CRC patients exhibited hypermethylated BEND5. Real-time
      reverse transcription PCR identified that BEND5 mRNA expression was downregulated
      in 68% (32/47) of the analyzed samples. BEND5 hypermethylation was associated
      with poor overall survival (OS) in Taiwan patients with early-stage CRC (P =
      0.037). In a CRC tissue set from South Korea, OS was higher in patients with high
      BEND5 protein expression than in those with low BEND5 protein expression (P =
      0.037) by using immunohistochemistry assays. Consistently, BEND5 hypermethylation
      was associated with poor OS in patients with early-stage CRC in The Cancer Genome
      Atlas (TCGA) data set (P = 0.003). Multivariate Cox proportional hazards
      regression analysis further supported that hypermethylation of BEND5 genes was
      significantly associated with OS in Taiwan and TCGA CRC patients (P = 0.023 and
      0.033, respectively). Finally, the cell model assay with transient transfection
      of BEND5 or si-BEND5 knockdown indicated that BEND5 inhibited cancer cell
      proliferation. In conclusion, epigenetic alteration in the candidate TSG BEND5
      contributes to colorectal cancer development and is a prognostic marker of CRC.

PMID- 29371917
TI  - Cell-surface marker discovery for lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths in the United States. Novel
      lung cancer targeted therapeutic and molecular imaging agents are needed to
      improve outcomes and enable personalized care. Since these agents typically
      cannot cross the plasma membrane while carrying cytotoxic payload or imaging
      contrast, discovery of cell-surface targets is a necessary initial step. Herein,
      we report the discovery and characterization of lung cancer cell-surface markers
      for use in development of targeted agents. To identify putative cell-surface
      markers, existing microarray gene expression data from patient specimens were
      analyzed to select markers with differential expression in lung cancer compared
      to normal lung. Greater than 200 putative cell-surface markers were identified as
      being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12,
      CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected
      based on differential mRNA expression in lung tumors vs. non-neoplastic lung
      samples and other normal tissues, and other considerations involving known
      biology and targeting moieties. Protein expression was confirmed by
      immunohistochemistry (IHC) staining and scoring of patient tumor and normal
      tissue samples. As further validation, marker expression was determined in lung
      cancer cell lines using microarray data and Kaplan-Meier survival analyses were
      performed for each of the markers using patient clinical data. High expression
      for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was
      significantly associated with worse survival. These markers should be useful for
      the development of novel targeted imaging probes or therapeutics for use in
      personalized care of lung cancer patients.

PMID- 29371921
TI  - Identification of MALT1 as both a prognostic factor and a potential therapeutic
      target of regorafenib in cholangiocarcinoma patients.
AB  - Intrahepatic cholangiocarcinoma (CCA) is an aggressive cancer that lacks an
      effective targeted therapy. Here, we assessed the therapeutic efficacy of
      regorafenib in CCA, as well as elucidated its underlying mechanism. We first
      demonstrated that regorafenib not only inhibited growth but also induced
      apoptosis in human CCA cells. Subsequently, we used in silico approaches to
      identify MALT1 (Mucosa-associated lymphoid tissue protein 1), which plays an
      important role in activating NF-kappaB, as a potential target of regorafenib.
      Overexpression of Elk-1, but not Ets-1, in HuCCT1 cells markedly reduced their
      sensitivity to regorafenib, which might be attributed to a significant increase
      in MALT1 levels. Our results further demonstrated that this drug drastically
      inhibited MALT1 expression by suppressing the Raf/Erk/Elk-1 pathway. The efficacy
      of regorafenib in decreasing in vivo CCA growth was confirmed in animal models.
      Regorafenib efficacy was observed in two MALT1-positive CCA patients who failed
      to respond to several other lines of therapy. Finally, MALT1 was also identified
      as an independent poor prognostic factor for patients with intrahepatic CCA. In
      conclusion, our study identified MALT1 to be a downstream mediator of the
      Raf/Erk/Elk-1 pathway and suggested that MALT1 may be a new therapeutic target
      for successful treatment of CCA by regorafenib.

PMID- 29371922
TI  - Helicobacter pylori CagA protein activates Akt and attenuates chemotherapeutics
      induced apoptosis in gastric cancer cells.
AB  - Infection with cagA-positive Helicobacter pylori is associated with a higher risk
      of gastric cancer. The cagA gene product, CagA, is translocated into gastric
      epithelial cells and perturbs host cellular biological functions. Etoposide, a
      topoisomerase II inhibitor widely used to couple DNA damage to apoptosis, is a
      common cytotoxic agent used for advanced gastric cancer. We investigate the
      effect of CagA on etoposide-induced apoptosis in gastric cancer cells to
      elucidate whether CagA play a role in gastric carcinogenesis via impairing DNA
      damage-dependent apoptosis. AGS cell lines stably expressing CagA isolated from
      H. pylori 26695 strain were established. In the presence of etoposide, viability
      of parental AGS cells was decreased in a time-and dose-dependent manner, whereas
      CagA-expressing AGS cells were less susceptible to etoposide induced cell-killing
      effect. Suppression of etoposide-induced apoptosis was shown in CagA-expressing
      but not in parental AGS cells by DNA fragmentation, cell cycle, and annexin-V
      assays. This inhibitory effect of etoposide-induced apoptosis conferred by CagA
      was also demonstrated in SCM1 and MKN45 gastric cancer cell lines, with two
      additional chemotherapeutics, 5-FU and cisplatin. The effect of Akt activation on
      inhibition of etoposide-induced cytotoxicity by CagA was also evaluated. CagA
      expression and etoposide administration activate Akt in a dose-dependent manner.
      Enhancement of etoposide cytotoxicity by a PI-3-kinase inhibitor, LY294002, was
      evident in parental but was attenuated in CagA-expressing AGS cells. CagA may
      activate Akt, either in the absence or presence of etoposide, potentially
      contributing to gastric carcinogenesis associated with H. pylori infection and
      therapeutic resistance by impairing DNA damage-dependent apoptosis.

PMID- 29371923
TI  - Targeting the PTTG1 oncogene impairs proliferation and invasiveness of melanoma
      cells sensitive or with acquired resistance to the BRAF inhibitor dabrafenib.
AB  - The pituitary tumor transforming gene 1 (PTTG1) is implicated in tumor growth,
      metastasis and drug resistance. Here, we investigated the involvement of PTTG1 in
      melanoma cell proliferation, invasiveness and response to the BRAF inhibitor
      (BRAFi) dabrafenib. We also preliminary assessed the potential value of
      circulating PTTG1 protein to monitor melanoma patient response to BRAFi or to
      dabrafenib plus trametinib. Dabrafenib-resistant cell lines (A375R and SK-Mel28R)
      were more invasive than their drug-sensitive counterparts (A375 and SK-Mel28),
      but expressed comparable PTTG1 levels. Dabrafenib abrogated PTTG1 expression and
      impaired invasion of the extracellular matrix (ECM) in A375 and SK-Mel28 cells.
      In contrast, it affected neither PTTG1 expression in A375R and SK-Mel28R cells,
      nor ECM invasion in the latter cells, while further stimulated A375R cell
      invasiveness. Assessment of proliferation and ECM invasion in control and PTTG1
      silenced A375 and SK-Mel28 cells, exposed or not to dabrafenib, demonstrated that
      the inhibitory effects of this drug were, at least in part, dependent on its
      ability to down-regulate PTTG1 expression. PTTG1-silencing also impaired
      proliferation and invasiveness of A375R and SK-Mel28R cells, and counteracted
      dabrafenib-induced stimulation of ECM invasion in A375R cells. Further
      experiments performed in A375R cells indicated that PTTG1-silencing impaired cell
      invasiveness through inhibition of MMP-9 and that PTTG1 expression and ECM
      invasion could be also reduced by the CDK4/6 inhibitor LEE011. PTTG1 targeting
      might, therefore, represent a useful strategy to impair proliferation and
      metastasis of melanomas resistant to BRAFi. Circulating PTTG1 also appeared to
      deserve further investigation as biomarker to monitor patient response to
      targeted therapy.

PMID- 29371924
TI  - PTEN loss and level of HER2 amplification is associated with trastuzumab
      resistance and prognosis in HER2-positive gastric cancer.
AB  - Background: Trastuzumab is an active agent against human epidermal growth factor
      receptor 2 (HER2)-positive gastric cancer (GC). This study aimed to characterize
      resistance to trastuzumab-based front-line chemotherapy in HER2+ GC patients and
      to establish factors predictive of this resistance. Results: Among 129 HER2+ GC
      patients, 25% displayed rapid disease progression within 4 months from initiation
      of therapy. These patients showed a higher rate of signet ring cell histology,
      bone metastasis, poor performance status, frequent loss of PTEN expression, and
      low HER2 amplification index compared with patients who were progression-free for
      at least 4 months. In contrast, there was no significant difference in the
      frequency of the PIK3R1 variant. Multivariate analyses confirmed two independent
      molecular predictors for trastuzumab resistance: loss of PTEN expression and low
      HER2 amplification index (<5). Patients with one or both molecular predictors at
      diagnosis exhibited worse progression-free and overall survival compared to those
      without risk factors (p < 0.001 and p = 0.001, respectively). Conclusion: In
      HER2+ GC patients, loss of PTEN expression and low HER2 AI correlated with
      resistance to trastuzumab-based therapy and dismal prognosis. Since patients
      harboring these molecular predictors are unlikely to respond to trastuzumab-based
      therapy, other novel therapeutic targets needed to be considered. Methods: HER2+
      GC patients who were treated with trastuzumab in combination with either 5
      fluorouracil/cisplatin or capecitabine/cisplatin were enrolled. Clinicopathologic
      features and molecular alterations of HER2, phosphoinositide 3-kinase regulatory
      subunit 1 (PIK3R1), and phosphatase and tensin homolog (PTEN) were correlated
      with treatment outcome. Factors predictive of resistance were also explored.

PMID- 29371925
TI  - The glucose and lipid metabolism reprogramming is grade-dependent in clear cell
      renal cell carcinoma primary cultures and is targetable to modulate cell
      viability and proliferation.
AB  - Clear cell renal cell carcinoma (ccRCC) has a poor prognosis despite novel
      biological targeted therapies. Tumor aggressiveness and poor survival may
      correlate with tumor grade at diagnosis and with complex metabolic alterations,
      also involving glucose and lipid metabolism. However, currently no grade-specific
      metabolic therapy addresses these alterations. Here we used primary cell cultures
      from ccRCC of low- and high-grade to investigate the effect on energy state and
      reduced pyridine nucleotide level, and on viability and proliferation, of
      specific inhibition of glycolysis with 2-deoxy-D-glucose (2DG), or fatty acid
      oxidation with Etomoxir. Our primary cultures retained the tissue grade-dependent
      modulation of lipid and glycogen storage and aerobic glycolysis (Warburg effect).
      2DG affected lactate production, energy state and reduced pyridine nucleotide
      level in high-grade ccRCC cultures, but the energy state only in low-grade.
      Rather, Etomoxir affected energy state in high-grade and reduced pyridine
      nucleotide level in low-grade cultures. Energy state and reduced pyridine
      nucleotide level were evaluated by ATP and reduced 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium (MTT) dye quantification, respectively. 2DG treatment
      impaired cell proliferation and viability of low-grade ccRCC and normal cortex
      cultures, whereas Etomoxir showed a cytostatic and cytotoxic effect only in high
      grade ccRCC cultures. Our data indicate that in ccRCC the Warburg effect is a
      grade-dependent feature, and fatty acid oxidation can be activated for different
      grade-dependent metabolic needs. A possible grade-dependent metabolic therapeutic
      approach in ccRCC is also highlighted.

PMID- 29371926
TI  - A natural inhibitor of kidney-type glutaminase: a withanolide from Physalis
      pubescens with potent anti-tumor activity.
AB  - Kidney-type glutaminase (KGA), a mitochondrial enzyme converting glutamine to
      glutamate for energy supply, was over-expressed in many cancers and had been
      regarded as a promising therapeutic target in recent years. Structure-based
      virtual ligand screening predicted physapubescin K, a new withanolide from
      Physalis pubescens, to be potential KGA inhibitor. Enzyme activity inhibition
      assays and microscale thermophoresis experiments had demonstrated the efficiency
      and specificity of physapubescin K targeting KGA. Additionally, physapubescin K
      exhibited potent proliferation inhibitory effects on a panel of human cancer cell
      lines, such as SW1990 and HCC827-ER. It blocked glutamine metabolism in SW1990
      with increasing intracellular level of glutamine and decreasing glutamate and its
      downstream metabolites. Physapubescin K also significantly inhibited the tumor
      growth in a SW1990 xenograft mouse model. Interestingly, physapubescin K could
      reverse the resistance of HCC827-ER cells to erlotinib and synergize with the
      hexokinase 2 inhibitor to markedly enhance the inhibition of SW1990 cell
      proliferation.

PMID- 29371927
TI  - Independent replication of polymorphisms predicting toxicity in breast cancer
      patients randomized between dose-dense and docetaxel-containing adjuvant
      chemotherapy.
AB  - Introduction: Although pharmacogenomics has evolved substantially, a predictive
      test for chemotherapy toxicity is still lacking. We compared the toxicity of
      adjuvant dose-dense doxorubicin-cyclophosphamide (ddAC) and docetaxel-doxorubicin
      cyclophosphamide (TAC) in a randomized multicenter phase III trial and replicated
      previously reported associations between genotypes and toxicity. Results: 646
      patients (97%) were evaluable for toxicity (grade 2 and higher). Whereas AN was
      more frequent after ddAC (P < 0.001), TAC treated patients more often had PNP (P
      < 0.001). We could replicate 2 previously reported associations: TECTA (rs1829;
      OR 4.18, 95% CI 1.84-9.51, P = 0.001) with PNP, and GSTP1 (rs1138272; OR 2.04,
      95% CI 1.13-3.68, P = 0.018) with PNP. Materials and methods: Patients with pT1
      3, pN0-3 breast cancer were randomized between six cycles A60C600 every 2 weeks
      or T75A50C500 every 3 weeks. Associations of 13 previously reported single
      nucleotide polymorphisms (SNPs) with the most frequent toxicities: anemia (AN),
      febrile neutropenia (FN) and peripheral neuropathy (PNP) were analyzed using
      logistic regression models. Conclusions: In this independent replication, we
      could replicate an association between 2 out of 13 SNPs and chemotherapy
      toxicities. These results warrant further validation in order to enable tailored
      treatment for breast cancer patients.

PMID- 29371928
TI  - Differentially expressed mRNAs, lncRNAs, and miRNAs with associated co-expression
      and ceRNA networks in ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by
      systemic inflammation and pathological osteogenesis. However, the genetic
      etiology of AS remains largely unknown. This study aimed to explore the potential
      role of coding and noncoding genes in the genetic mechanism of AS. Using
      microarray analyses, this study comprehensively compared lncRNA, microRNA, and
      mRNA profiles in hip joint ligament tissues from patients with AS and controls. A
      total of 661 lncRNAs, 574 mRNAs, and 22 microRNAs were differentially expressed
      in patients with AS compared with controls. Twenty-two of these genes were then
      validated using real-time polymerase chain reaction. Gene ontology and pathway
      analyses were performed to explore the principal functions of differentially
      expressed genes. The pathways were involved mainly in immune regulation,
      intercellular signaling, osteogenic differentiation, protein synthesis, and
      degradation. Gene signal transduction network, coding-noncoding co-expression
      network, and competing endogenous RNA expression network were constructed using
      bioinformatics methods. Then, two miRNAs, miR-17-5p and miR-27b-3p, that could
      increase the osteogenic differentiation potentials of ligament fibroblasts were
      identified. Finally, differentially expressed, five lncRNAs, four miRNAs, and
      five mRNAs were validated using quantitative real-time polymerase chain reaction.
      These results suggested that mRNAs, lncRNAs, and microRNAs were involved in AS
      pathogenesis. The findings might help characterize the pathogenesis of AS and
      provide novel therapeutic targets for patients with AS in the future.

PMID- 29371929
TI  - miR-769-5p suppressed cell proliferation, migration and invasion by targeting
      TGFBR1 in non-small cell lung carcinoma.
AB  - MicroRNAs (miRNAs) are key regulators of multiple cancers, including non-small
      cell lung carcinoma (NSCLC). The aim of this study was to determine the
      expression pattern of miR-769-5p in NSCLC and to investigate its biological role
      during tumorigenesis. We showed that miR-769-5p was significantly downregulated
      and predicted poor prognosis in NSCLC compared with corresponding normal tissues.
      We then investigated its function and found that miR-769-5p significantly
      inhibited cell proliferation, migration and invasion in vitro and reduced tumor
      growth and metastasis in vivo. Furthermore, we explored the molecular mechanisms
      by which miR-769-5p contributes to NSCLC suppression and identified TGFBR1 as a
      direct target gene of miR-769-5p. Finally, we showed that TGFBR1 had opposite
      effects to those of miR-769-5p on lung cancer cells, suggesting that miR-769-5p
      might inhibit lung tumorigenesis by silencing TGFBR1. Taken together, our results
      demonstrated that miR-769-5p plays a pivotal role in NSCLC by inhibiting cell
      proliferation, migration and invasion by targeting TGFBR1.

PMID- 29371930
TI  - Identification and comparison of novel circular RNAs with associated co
      expression and competing endogenous RNA networks in pulmonary tuberculosis.
AB  - Pulmonary tuberculosis (PTB) is caused by Mycobacterium tuberculosis and is one
      of the most serious diseases worldwide. Circular RNAs (circRNAs) are a large
      class of non-coding RNAs that were identified with potential regulatory roles in
      disease pathogenesis and progression. In this study, we used whole transcriptome
      sequencing to identify circRNAs from 3 PTB patients and 3 healthy individuals to
      determine the expression pattern of circRNAs in blood and the circRNA molecular
      regulatory networks in PTB pathogenesis. One hundred and seventy differentially
      expressed (>= 2-fold change) circRNAs were dysregulated in PTB, compared with in
      healthy individuals. Quantitative real-time polymerase chain reaction was used to
      validate the RNA sequencing analysis from 20 PTB patients, and the results were
      consistent with the sequencing data. Gene Ontology annotation and Kyoto
      Encyclopedia of Genes and Genomes pathway analysis were applied to explore the
      potential circRNA functions of the significantly deregulated genes. Several
      immunity pathways, including endocytosis pathways in cancer, mitogen-activated
      protein kinase signaling pathway, human T-lymphotropic virus type 1 infection,
      and ubiquitin-mediated proteolysis, were involved in PTB pathogenesis. Competing
      endogenous RNAs (ceRNA) were constructed and inferred that aberrant expression of
      circRNA-associated ceRNA resulted in extensive variation in gene expression by
      miRNA-mediated circRNA-mRNA crosstalk interactions. Our study revealed that the
      circRNA-miRNA-mRNA network may shed light on the biological functions of circRNAs
      in PTB and provide useful information for exploring potential roles of circRNA in
      PTB.

PMID- 29371931
TI  - Progesterone and calcitriol reduce invasive potential of endometrial cancer cells
      by targeting ARF6, NEDD9 and MT1-MMP.
AB  - Previously, we have demonstrated that progesterone and calcitriol synergistically
      inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and
      causing cell cycle arrest. Metastasis is the main reason of mortality in cancer
      patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell
      expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix
      Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and
      metastasis. We examined the effects of progesterone, calcitriol and progesterone
      calcitriol combination on metastasis promoting proteins in endometrial cancer.
      Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial
      tumors and in cancer cell lines compared to normal tissues and immortalized EM
      E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins
      significantly inhibited the invasiveness of the cancer cells. The expression
      levels of all three proteins was reduced with progesterone and progesterone
      calcitriol combination treatment, whereas calcitriol alone showed no effect on
      their expression but moderately decreased MT1-MMP activity. Fluorescence
      microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol
      treated endometrial cancer cells. However, progesterone and calcitriol
      progesterone combination treatment revealed MT1-MMP in the cytoplasm.
      Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9,
      and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both
      progesterone and progesterone-calcitriol combination treated cells as well as in
      MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with
      progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer
      dissemination and may have therapeutic benefits for endometrial cancer patients.

PMID- 29371932
TI  - Identification of novel genes in aging osteoblasts using next-generation
      sequencing and bioinformatics.
AB  - During the aging process, impaired osteoblastic function is one key factor of
      imbalanced bone formation and age-related bone loss. The aim of this study is to
      explore the differentially expressed genes in normal and aged osteoblasts and to
      identify genes potentially involved in age-related alteration in bone physiology.
      Based on next generation sequencing and bioinformatics analysis, 12
      differentially expressed microRNAs and 22 differentially expressed genes were
      identified. Up-regulation of miR-204-5p was validated in an array of osteoporotic
      hip fracture in the Gene Expression Omnibus database (GSE74209). The putative
      targets for miR-204-5p were Kruppel-like factor 7 (KLF7) and SRY-box 11 (SOX11).
      Ingenuity Pathway Analysis identified SOX11, involved in osteoarthritis pathway
      and differentiation of osteoblasts, together with miR-204-5p, a potential
      upstream regulator, suggesting the critical role of miR-204-5p-SOX11 regulation
      in the aging process of human bones. In addition, as semaphorin 3A (SEMA3A) and
      ephrin type-A receptor 5 (EPHA5) were involved in nervous system related
      biological functions, we postulated a potential linkage between SEMA3A, EPHA5 and
      development of neurogenic heterotopic ossification. Our findings implicate new
      candidate genes in the diagnosis of geriatric musculoskeletal disorders, and
      provide novel insights that may contribute to the elaboration of new biomarkers
      for neurogenic heterotopic ossification.

PMID- 29371933
TI  - Induction of oxidative stress and cell apoptosis by selenium: the cure against
      oral carcinoma.
AB  - Oral carcinoma (OC) remains one of the most difficult malignancies to cure.
      selenium (Se) is an essential trace mineral for human and animals, but high
      concentrations of Se induce apoptosis and oxidative effects. Although cell
      apoptosis has been evidenced as a critical mechanism mediating the anticancer
      activity of Se, the underlying molecular mechanisms remain elusive. To explore
      the role of Se in rat OC, we examined the weather the oxidative stress-mediated
      apoptotic pathway induced by Se was involved in the development of OC. In this
      study, we successfully constructed the OC rat model by 4-Nitroquinoline-1-oxide
      (4-NQO) exposure which reflected from histopathological observations. Se-induced
      the productions of methane dicarboxylic aldehyde (MDA) and reactive oxygen
      species (ROS), which was accompanied by the inhibition of superoxide dismutase
      (SOD) both in vivo and vitro. The anti-apoptotic gene (Bcl-2) was down-regulated
      and pro-apoptosis members (Bax, Bak, Cyt-c, caspase9 and caspase3) were up
      regulated by Se in OC cells. Meanwhile, we also found that Se could strongly
      inhibited the cell proliferation of OC lines in vitro. These results suggested
      that excessive Se could effectively cause oxidative stress and induce apoptosis
      in OC cells, as a result the OC was also inhibited to some extent. Therefore, the
      information presented in this study is believed to be helpful in supplementing
      data for further therapy of OC.

PMID- 29371934
TI  - Long non-coding RNA Lucat1 is a poor prognostic factor and demonstrates malignant
      biological behavior in clear cell renal cell carcinoma.
AB  - Background: Many long intergenic noncoding RNAs (lincRNAs) are encoded in the
      human genome. However, their biological functions, molecular mechanisms and
      prognostic values associated with clear cell renal cell carcinoma (ccRCC) have
      yet to be elucidated. Methods: We screened the lncRNAs' profile in ccRCC from The
      Cancer Genome Atlas (TCGA) database, and selected Lucat1 for further study. MTS,
      colony formation assay and transwell assay were performed to examine the effect
      of Lucat1 on proliferation and metastasis of ccRCC. The Chip and Rip assay was
      performed to verify that Lucat1 can bind to polycomb PRC2 complex and suppress
      p57 expression. Results: In this study, we found that lncRNA Lucat1 expression
      was significantly up regulated in tumor tissues compared to matched adjacent non
      tumor tissues. The Lucat1 expression level was also associated with grade, the
      clinical pathological stage and the survival time. Functional assays showed that
      Lucat1 can promote renal cancer cell proliferation in vitro and in vivo. Further
      analysis showed that Lucat1 can bind to polycomb PRC2 complex and suppress p57
      expression. Conclusions: Taken together, our results suggest that Lucat1, as a
      regulator of proliferation, may serve as a candidate prognostic biomarker and
      target for novel therapies in human ccRCC.

PMID- 29371935
TI  - Ubiquitin carboxyl-terminal hydrolase isozyme L5 inhibits human glioma cell
      migration and invasion via downregulating SNRPF.
AB  - Ubiquitin C-terminal Hydrolase-L5 (UCH-L5/UCH37), a member of the deubiquitinases
      (DUBs), suppresses protein degeneration via removing ubiquitin from the distal
      subunit of the polyubiquitin chain. The activity of UCH-L5 is enhanced when UCH
      L5 combines with proteasome 19S regulatory subunit by Rpn13/Admr1 receptor and
      inhibited when UCH-L5 interacts with NFRKB. But the role of UCH-L5 in gliomas
      remains unknown. In this study, analysis of 19 frozen and 51 paraffin-embedded
      clinic pathological cases showed that UCH-L5 expression in glioma tissues was
      lower than normal brain tissues. In vitro, we found that UCH-L5 could inhibit
      migration and invasion of U87MG and U251 cells. It has been reported that the
      expression of SNRPN, SNRPF, and CKLF was abnormal in gliomas or other tumors. We
      also found that SNRPF-siRNA, SNRPN-siRNA and CKLF-siRNA could inhibit migration
      and invasion of U87MG cells. And knockdown of UCH-L5 expression improved both
      mRNA expression and protein level of SNRPF. The relationship between UCH-L5 and
      SNRPF was further confirmed in 293T cells. Our study showed that UCH-L5 could
      inhibit migration and invasion of glioma cells via down regulating expression of
      SNRPF. And the above findings suggest that UCH-L5 may inhibit occurrence and
      metastasis of gliomas.

PMID- 29371936
TI  - LncRNA TUG1 sponges miR-145 to promote cancer progression and regulate glutamine
      metabolism via Sirt3/GDH axis.
AB  - Long noncoding RNAs (lncRNAs) are important regulators in cancer progression.
      Deregulation of the lncRNA taurine upregulated gene 1 (TUG1) predicts poor
      prognosis and is implicated in the development of several cancers. In this study,
      we investigated the role of TUG1 in the pathogenesis of intrahepatic
      cholangiocarcinoma (ICC). We found that TUG1 is upregulated in ICC samples, which
      correlates with poor prognosis and adverse clinical pathological characteristics.
      Knockdown of TUG1 inhibited the proliferation, motility, and invasiveness of
      cultured ICC cells, and decreased tumor burden in a xenograft mouse model. When
      we explored the mechanisms underlying these effects, we found that TUG1 acts as
      an endogenous competing RNA (ceRNA) that 'sponges' miR-145, thereby preventing
      the degradation of Sirt3 mRNA and increasing expression of Sirt3 and GDH
      proteins. Accordingly, glutamine consumption, alpha-KG production, and ATP levels
      were dramatically decreased by TUG1 knockdown in ICC cells, and this effect was
      reversed by miR-145 inhibition. These findings indicate that the TUG1/miR
      145/Sirt3/GDH regulatory network may provide a novel therapeutic strategy for
      treatment of ICC.

PMID- 29371937
TI  - Molecular targeting of cell-permeable peptide inhibits pancreatic ductal
      adenocarcinoma cell proliferation.
AB  - Background: Chromosome 16 open reading frame 74 (C16orf74) is highly expressed in
      pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell
      proliferation and invasion through binding to calcineurin (CN). Therefore,
      C16orf74 is a good target for the development of a PDAC treatment. A cell
      permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN
      interaction was designed to examine whether this peptide can inhibit PDAC cell
      proliferation in vitro and in vivo. Method: TheDN-C16orf74 peptide, which
      corresponds to the portion of C16orf74 that interacts with CN, was synthesized,
      and we assessed its anti-tumor activity in proliferation assays with human PDAC
      cells and the underlying molecular signaling pathway. Using an orthotopic
      xenograft model of PDAC, we treated mice intraperitoneally with phosphate
      buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor
      suppressive effects. Result: DN-C16orf74 inhibited the binding of C16orf74 to CN
      in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation,
      and the level of suppression depended on the expression levels of C16orf74 in
      vitro. DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft
      model. Furthermore, the tumor-suppressive effect was associated with inhibition
      of the phosphorylation of Akt and mTOR. Conclusion: The cell-permeable peptide DN
      C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo.

PMID- 29371938
TI  - Large-scale copy number analysis reveals variations in genes not previously
      associated with malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive tumor that is often
      causally associated with asbestos exposure. Comparative genomic hybridization
      techniques and arrays demonstrated a complex set of copy number variations (CNVs)
      in the MPM-genome. These techniques however have a limited resolution, throughput
      and flexibility compared to next-generation sequencing platforms. In this study,
      the presence of CNVs in the MPM-genome was investigated using an MPM-cohort (N =
      85) for which genomic microarray data are available through 'The Cancer Genome
      Atlas' (TCGA). To validate these results, the genomes of MPMs and matched normal
      samples (N = 21) were analyzed using low-pass whole genome sequencing on an
      'Illumina HiSeq' platform. CNVs were detected using in-house developed analysis
      pipelines and frequencies of copy number loss and gain were calculated. In both
      datasets, losses on chromosomes 1, 3, 4, 6, 9, 13 and 22 and gains on chromosomes
      1, 5, 7 and 17 were found in at least 25% and 15% of MPMs, respectively. Besides
      the well-known MPM-associated genes, CDKN2A, NF2 and BAP1, other interesting
      cancer-associated genes were listed as frequently involved in a copy number loss
      (e.g. EP300, SETD2 and PBRM1). Moreover, four cancer-associated genes showed a
      high frequency of copy number gain in both datasets (i.e. TERT, FCGR2B, CD79B and
      PRKAR1A). A statistically significant association between overall survival and
      the presence of copy number loss in the CDKN2A-containing region was observed in
      the TCGA-set. In conclusion, recurrent CNVs were detected in both datasets,
      occurring in regions harboring known MPM-associated genes and genes not
      previously linked to MPM.

PMID- 29371939
TI  - Elucidating respective functions of two domains BIR and C-helix of human IAP
      survivin for precise targeted regulating mitotic cycle, apoptosis and autophagy
      of cancer cells.
AB  - Survivin was the smallest member of the IAP family, which was over expressed in
      many different cancers, and considered to be a promising hot target for cancer
      therapy, and our previous study demonstrated that multiple dominant negative
      mutants from full-length survivin could have many complex effects on cancer
      cells, such as cell cycle, apoptosis, and autophagy. But it was not yet known
      what role the two main domains played in those functions, which would be very
      important for the design of targeted anticancer drugs and for the interpretation
      of their molecular mechanisms. In this study, based on preparation the two parts
      (BIR domain and CC domain) of survivin by genetic engineering and cell
      characterization assay, we discovered that BIR (T34A)-domain peptide could
      inhibit Bcap-37 cells growth in a dose- and time-dependent manner, increase the
      proportion of G2/M phase, and induce caspase-dependent apoptosis via the
      mitochondrial pathway. While CC (T117A)-domain peptide increased the proportion
      of S-phase cells and increased the level of the autophagy marker protein LC3B
      significantly. These further experiments confirmed that TAT-BIR (T34A) peptide
      could be used to inhibit cell proliferation, promote apoptosis, and block
      mitosis, and TAT-CC (T117A) peptide showed mainly to promote autophagy, process
      of DNA replication, and mitosis to breast cancer cells. This research will lay
      the foundation for interpreting the multifunction mechanism of survivin in cell
      fates, further make senses in developing the anticancer drugs targeting it
      precisely and efficiently.

PMID- 29371940
TI  - The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic
      carcinoma growth.
AB  - Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is involved in
      the development and progression of many tumors. In this study, XIST was
      specifically upregulated in pancreatic carcinoma tissues and cell lines; a higher
      XIST expression was correlated to poorer clinicopathologic features. After XIST
      knockdown, the proliferation of PC cell lines was suppressed and cell cycle
      stagnated in G1 phase; XIST knockdown also reduced the protein levels of
      inhibitor of apoptosis-stimulating protein of p53 (iASPP) and Cyclin-dependent
      kinase 1 (CDK1), increased the protein level of P21, a potent CDK inhibitor. In
      PC cell lines, XIST and miR-140/miR-124, two tumor-associated miRNAs, could
      inversely regulate each other, respectively; miR-140/miR-124 could bind to XIST
      and the 3'UTR of PPP1R13L, respectively. XIST and miR-140/miR-124 exerted
      opposite effects on iASPP, CDK1, P21 and P27 proteins; whereas the effects of LV
      sh-XIST on the indicated protein levels could be partially reversed by miR-140
      and/or miR-124 inhibitor. In PC tissues, miR-140 and miR-124 expression was down
      regulated, iASPP and CDK1 mRNA expression was up-regulated. XIST positively
      correlated with iASPP and CDK1, inversely correlated with miR-140 and miR-124,
      respectively. Taken together, our data indicated that XIST might be an oncogenic
      lncRNA that promoted proliferation of PC cell line through inhibiting miR-140/miR
      124 expression and promoting cell cycle-related factor expression, and could be
      regarded as a therapeutic target in human pancreatic carcinoma.

PMID- 29371941
TI  - Doxorubicin-fucoidan-gold nanoparticles composite for dual-chemo-photothermal
      treatment on eye tumors.
AB  - The current research demonstrates the feasible biomedical application of AuNPs
      coated with doxorubicin (Dox)-loaded fucoidan (Fu) for dual-chemotherapy and
      photothermal treatment (PTT) on eye tumors in vitro and in vivo. Marine-derived
      Fu was used as a capping agent to achieve high photostability for AuNPs, and Dox
      as a FDA-approved anti-cancer drug was added to induce chemotherapy. The
      synthesized Dox-Fu@AuNPs exhibited high cytotoxicity on the tumor cells and
      strong light absorption for temperature increase in vitro. After intratumoral
      injection of Dox-Fu@AuNPs in the rabbit eye tumors, PTT-assisted Dox-Fu@AuNPs
      entailed the complete removal of the eye tumors without recurrence for 14 days
      after the treatment. Photoacoustic image contrast from the tumor regions was
      enhanced due to selective light absorption by the administered Dox-Fu@AuNPs.
      Therefore, the proposed Dox-Fu@AuNPs can be a potential nano-theranostic material
      for treating and diagnosing the eye tumors.

PMID- 29371942
TI  - Dietary quercetin potentiates the antiproliferative effect of interferon-alpha in
      hepatocellular carcinoma cells through activation of JAK/STAT pathway signaling
      by inhibition of SHP2 phosphatase.
AB  - Type I interferons (IFN-alpha/beta) have broad and potent immunoregulatory and
      antiproliferative activities, which are negatively regulated by Src homology
      domain 2 containing tyrosine phosphatase-2 (SHP-2). Inhibition of SHP2 by small
      molecules may be a new strategy to enhance the effcacy of type I IFNs. Using an
      in vitro screening assay for new inhibitors of SHP2 phosphatase, we found that
      quercetin was a potent inhibitor of SHP2. Computational modeling showed that
      quercetin exhibited an orientation favorable to nucleophilic attack in the
      phosphatase domain of SHP2. Quercetin enhanced the phosphorylation of signal
      transducer and activator of transcription proteins 1 (STAT1) and promoted
      endogenous IFN-alpha-regulated gene expression. Furthermore, quercetin also
      sensitized the antiproliferative effect of IFN-alpha on hepatocellular carcinoma
      HepG2 and Huh7 cells. The overexpression of SHP2 attenuated the effect of
      quercetin on IFN-alpha-stimulated STAT1 phosphorylation and antiproliferative
      effect, whereas the inhibition of SHP2 promoted the effect of quercetin on IFN
      alpha-induced STAT1 phosphorylation and antiproliferative effect. The results
      suggested that quercetin potentiated the inhibitory effect of IFN-alpha on cancer
      cell proliferation through activation of JAK/STAT pathway signaling by inhibiting
      SHP2. Quercetin warrants further investigation as a novel therapeutic method to
      enhance the efficacy of IFN-alpha/beta.

PMID- 29371943
TI  - Tumorablative conditioning regimen for haploidentical stem cell transplantation
      in 102 children with hematologic malignancies: a single-center experience.
AB  - Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) is widely
      carried out in China, and transplantation related complications decreased
      gradually with the transplant technology improving, and the overall survival(OS)
      increased year by year. However, relapse after transplantation is still one of
      the main causes of death in patients with hematological malignancy. In order to
      reduce the recurrence after HSCT, we set a tumorablative conditioning regimen
      (TAC ) regimen; the aim is as much as possible to eliminate the malignant clone
      to reduce the recurrence without increasing the conditioning toxicity. We
      retrospectively analyzed 102 cases of haplo-HSCT in our hospital from 2012 to
      2017. Ninety-eight out of the 99 (99.0%) patients achieved primary engraftment.
      The 2-year OS and disease free survival (DFS) are 81.4% (83/102) and 77.45%
      (79/102). The cumulative incidence of leukemia relapse is 16.2% (16/99), Twenty
      nine patients developed II-IV acute graft-versus-host disease (aGVHD) (29%)
      within 100 days and only nine patients have grade III-IV aGVHD (9%) in measurable
      99 patients. The conditioning regimen was relatively well tolerated with limited
      regimen-related toxicity. The preliminary results show that TAC is safe and
      effective in haplo-HSCT of children with hematologic malignancies. This study
      will provide a clinical basis for the individualized conditioning regimen.

PMID- 29371944
TI  - Measurement of tumor volume is not superior to diameter for prediction of lymph
      node metastasis in early gastric cancer with minute submucosal invasion.
AB  - Background/Aim: The current indication for endoscopic resection in early gastric
      cancer (EGC) with minute (< 500 um) submucosal invasion is based on tumor
      diameter, which may be insufficient to predict lymph node metastasis (LNM). We
      investigated whether tumor volume might more accurately predict LNM in EGC with
      minute submucosal invasion. Materials and Methods: Among patients who underwent
      gastrectomy for gastric cancer, 346 with well/moderately differentiated EGC with
      submucosal invasion <500 um were evaluated. Three-dimensional tumor volume was
      calculated using an endoscopically resected specimen and compared with 1
      dimensional tumor diameter. Predictive ability of tumor diameter or volume for
      LNM was evaluated using receiver operating characteristic curve analysis.
      Results: Tumor diameter and volume predicted LNM with an area under the curve
      (AUC) of 0.567 and 0.589, respectively. AUC, sensitivity, specificity, positive
      and negative predictive values, and accuracy of the 2 models were not
      significantly different. Tumor diameter >= 3 cm showed a significant association
      with LNM (odds ratio [OR], 2.57; 95% confidence interval [CI], 1.01-6.57; P =
      0.049), whereas a tumor volume cutoff value of 752.8 cm3 showed no significant
      association with LNM (OR, 1.52; 95% CI, 0.59-3.88; P = 0.385). Conclusions: Tumor
      volume had no advantage over diameter for predicting LNM in well/moderately
      differentiated EGC with minute submucosal invasion.

PMID- 29371945
TI  - BICD1 expression, as a potential biomarker for prognosis and predicting response
      to therapy in patients with glioblastomas.
AB  - There is variation in the survival and therapeutic outcome of patients with
      glioblastomas (GBMs). Therapy resistance is an important challenge in the
      treatment of GBM patients. The aim of this study was to identify Temozolomide
      (TMZ) related genes and confirm their clinical relevance. The TMZ-related genes
      were discovered by analysis of the gene-expression profiling in our cell-based
      microarray. Their clinical relevance was verified by in silico meta-analysis of
      the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA)
      datasets. Our results demonstrated that BICD1 expression could predict both
      prognosis and response to therapy in GBM patients. First, high BICD1 expression
      was correlated with poor prognosis in the TCGA GBM cohort (n=523) and in the CGGA
      glioma cohort (n=220). Second, high BICD1 expression predicted poor outcome in
      patients with TMZ treatment (n=301) and radiation therapy (n=405). Third,
      multivariable Cox regression analysis confirmed BICD1 expression as an
      independent factor affecting the prognosis and therapeutic response of TMZ and
      radiation in GBM patients. Additionally, age, MGMT and BICD1 expression were
      combinedly utilized to stratify GBM patients into more distinct risk groups,
      which may provide better outcome assessment. Finally, we observed a strong
      correlation between BICD1 expression and epithelial-mesenchymal transition (EMT)
      in GBMs, and proposed a possible mechanism of BICD1-associated survival or
      therapeutic resistance in GBMs accordingly. In conclusion, our study suggests
      that high BICD1 expression may result in worse prognosis and could be a predictor
      of poor response to TMZ and radiation therapies in GBM patients.

PMID- 29371946
TI  - Episode-like pulse testosterone supplementation induces tumor senescence and
      growth arrest down-modulating androgen receptor through modulation of p-ERK1/2,
      pARser81 and CDK1 signaling: biological implications for men treated with
      testosterone replacement therapy.
AB  - Despite the growing body of knowledge showing that testosterone (T) may not
      significantly affect tumor progression in hypogonadal patients treated for
      prostate cancer (Pca), the use of this hormone in this population still remains
      controversial. The effects of continuous or pulsed T stimulation were tested in
      vitro and in vivo on androgen-sensitive Pca cell lines in order to assess the
      differential biological properties of these two treatment modalities. Pulsed T
      treatment resulted in a greater inhibition than continuous T supplementation of
      tumor growth in vitro and in vivo. The effects of pulsed T treatment on tumor
      growth inhibition, G0/G1 cell cycle arrest, and tumor senescence was more
      pronounced than those obtained upon continuous T treatments. Mechanistic studies
      revealed that G0/G1 arrest and tumor senescence upon pulsed T treatment were
      associated with a marked decrease in cyclin D1, c-Myc and SKp2, CDK4 and p-Rb
      levels and upregulation of p27 and p-ERK1/2. Pulsed, but not continuous, T
      supplementation decreased the expression levels of AR, p-ARser81 and CDK1 in both
      cellular models. The in vitro results were confirmed in an in vivo xenografts,
      providing evidence of a greater inhibitory activity of pulsed supraphysiological
      T supplementation than continuous treatment, both in terms of tumor volume and
      decreased AR, p-ARser81, PSA and CDK1 staining. The rapid cycling from
      hypogonadal to physiological or supra-physiological T intraprostatic
      concentrations results in cytostatic and senescence effects in preclinical models
      of androgen-sensitive Pca. Our preclinical evidence provides relevant new
      insights in the biology of Pca response to pulsed T supplementation.

PMID- 29371947
TI  - Programmed death-ligand 1 expression according to epidermal growth factor
      receptor mutation status in pretreated non-small cell lung cancer.
AB  - Background: Current clinical trials have suggested poorer efficacies of anti
      programmed death-1 (PD-1)/PD-ligand 1 (PD-L1) immunotherapies for non-small cell
      lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations,
      implying lower PD-L1 expression in EGFR-mutant NSCLC than in EGFR-wild type.
      Methods: We retrospectively analyzed correlation between PD-L1 expression and
      EGFR status in clinical samples of pretreated NSCLC. PD-L1 immunohistochemistry
      was performed using the 28-8 anti-PD-L1 antibody for tumor cell membrane
      staining. H-score was adopted to evaluate both percentage and intensity. We
      investigated H-scores >=1, >=5, and >=10 as PD-L1+ cut-offs. H-score >=10 was
      defined as strong PD-L1+. Results: We investigated 96 available histologic
      samples in 77 pretreated patients with NSCLC. Median H-score in EGFR-mutant
      samples (n=65) was 3 (range, 0-150), whereas EGFR-wild-type (n=31) was 8 (range,
      0-134) (p=0.0075). Using H-scores >=1, >=5, and >=10 cut-offs, incidence of PD
      L1+ in EGFR-mutant vs. EGFR-wild-type samples were: 85% (55/65) vs. 94% (29/31)
      (p=0.2159); 42% (27/65) vs. 74% (23/31) (p=0.0027); and 22% (14/65) vs. 48%
      (15/31) (p=0.0074), respectively. Patient-oriented (n=77) univariate analysis for
      strong PD-L1+ found age of sample (p=0.0226) and EGFR mutation status (p=0.0490)
      as significant factors. Multivariate analysis identified EGFR mutation status as
      the only significant factor (p=0.0121, odds ratio 2.99) for strong PD-L1+. H
      scores of PD-L1 expression varied in all 11 cases receiving multiple rebiopsies,
      and categories of positivity migrated in 10 (91%) of 11 patients. Conclusions: PD
      L1 expression was significantly lower in EGFR-mutant NSCLC samples than in EGFR
      wild-type samples. Its expression could be dynamic and affected by age of sample.

PMID- 29371948
TI  - Intrahepatic cholangiocarcinoma patients without indications of lymph node
      metastasis not benefit from lymph node dissection.
AB  - BACKGROUND: To investigate the necessity of routine lymph node dissection (LND)
      in intrahepatic cholangiocarcinoma (ICC) patients without indications of lymph
      node metastasis (LNM) preoperatively. METHODS: 422 consecutive ICC patients who
      undergone curative resection from January 2009 to December 2014 were enrolled and
      categorized as two groups (hepatectomy only or hepatectomy plus LND).
      Clinicopathologic data was compared between the groups by chi2 or Fisher's exact
      test. Overall survival (OS) and recurrence-free survival (RFS) were calculated by
      the Kaplan-Meier method and differences were analyzed using the log-rank test.
      Cox regression model was adopted for multivariable analysis. RESULTS: The median
      OS time of all 422 patients was 41.4 months. One-, 3-, and 5-year OS was 67%,
      47%, and 35%, respectively. A total of 73 patients had undergone curative
      resection combined with LND, of whom 20.5% (15/73) were confirmed lymph node
      positive pathologically. The clinicopathologic characteristics between LND and
      control groups showed no significant differences. Of the 422 patients, 271
      patients had recurrence. The recurrence rates were 65.8% for the LND group and
      63.9% for the non-LND group. Survival analysis revealed that, neither the OS (LND
      vs. non-LND: 32.2 months vs. 46.2 months; p = 0.16) nor the RFS (LND vs. non-LND:
      23.1 months vs. 17.0 months; p = 0.09) had significant difference. Multivariate
      analysis revealed that tumor size, tumor number, carbohydrate antigen19-9,
      carcinoembryonic antigen, and gamma-glutamyl transpeptidase were independent
      predictive factors for OS and RFS. CONCLUSION: Routine LND may not improve
      survival in resectable ICC patients with negative LNM diagnosis before operation.

PMID- 29371949
TI  - Cell activity during peripheral nerve defect repair process using a nerve
      scaffold.
AB  - Peripheral nerve defects, but not artificial nerves, are repaired by endogenous
      cells. We examined cell activity during the repair process in the presence of
      autologous nerves and artificial preparations in order to guide future artificial
      nerve fabrication. PLGA tubes, nerve scaffolds comprising a PLGA tube plus 6,000
      fibroin fibers, or autologous nerves were implanted into 10 mm rat sciatic nerve
      defects (n = 60 per group). Over a period of 1-20 weeks after nerve grafting,
      sections were stained and imaged to distinguish the cell types present and we
      quantified the recovery of motor and sensory function in the surgically implanted
      limb. We observed a decreasing trend in inflammatory cell and fibroblast counts
      over time which ranked in magnitude as: (PLGA group > nerve scaffold > autologous
      nerve> sham) and an opposite trend in Schwann cell counts. Differences in
      withdrawal time from hot water and static sciatic index (SSI) indicated that,
      after repair, sensory and motor function were best in the sham group, followed by
      the autologous group, the nerve scaffold group, and the PLGA group. These
      findings indicate that the inflammatory reaction is significant in the first two
      weeks after nerve grafting, followed by the rebirth of fibroblasts and Schwann
      cells, which guide axon regeneration. This inflammatory response was a
      fundamental stage of peripheral defect repair, but a weaker inflammatory response
      corresponded to better recovery of sensorimotor functional.

PMID- 29371950
TI  - Overexpression of miR-489 enhances efficacy of 5-fluorouracil-based treatment in
      breast cancer stem cells by targeting XIAP.
AB  - Population of cancer stem cells (CSCs) in breast cancer is reported to be
      resistant to chemotherapy. Furthermore, many cases of treatment failure are
      induced by the chemoresistance of CSCs in breast cancer patients. Therefore,
      novel strategies should be explored urgently to reverse drug-resistance in breast
      cancer stem cells (BCSCs). In this study, we isolated and cultured the BCSCs from
      the T-47D and SKBR3 breast cancer cell lines. We observed significant resistance
      to 5-fluorouracil in BCSCs. Mechanically, we found that expression of miR-489 was
      decreased in BCSCs. Furthermore, overexpression of miR-489 was found to increase
      the cytotoxicity of 5-fluorouracil to BCSCs. XIAP, a key anti-apoptotic protein,
      was proved to be the target of miR-489. We found that enforced expression of XIAP
      through its recombinant expression vector abolished the effect of miR-489 on
      reversing the 5-fluorouracil resistance. On the contrary, embelin, a XIAP
      specific inhibitor, was found to sensitize BCSCs to 5-fluorouracil similarly with
      miR-489. In summary, our data demonstrate that introduction with miR-489
      represents a novel strategy to enhance efficacy of 5-fluorouracil-based treatment
      in BCSCs.

PMID- 29371951
TI  - LKB1 loss cooperating with BRAF V600E promotes melanoma cell invasion and
      migration by up-regulation MMP-2 via PI3K/Akt/mTOR pathway.
AB  - The serine/threonine kinase LKB1, act as a tumor suppressor, has been reported in
      several sporadic cancers. However, how the loss of LKB1 promotes melanoma
      invasion and metastasis remains incompletely understood. In this study, we
      inactivated LKB1expression by RNA interference in BRAF mutation and wild type
      melanoma cells respectively. We found LKB1 inactivation cooperate with BRAF V600E
      lead to melanoma cells more aggressive by a series of experiments including wound
      scratch test, Transwell assay. While single alteration, either LKB1 loss or BRAF
      V600E, fails to enhance melanoma cells invasion ability. Mechanistically, LKB1
      loss synergism with BRAF V600E resulted in the activation of the PI3K/Akt/mTOR
      signaling pathway and significant up-regulation expression of MMP-2. In addition,
      LKB1 expression in human melanoma tissues was negatively associated with MMP-2
      expression in the presence of BRAF V600E. Thus, our findings indicate a probable
      explanation on LKB1 function as a tumor suppressor in melanoma and a new
      therapeutic strategy for melanoma by targeting on BRAF and LKB1 together.

PMID- 29371953
TI  - Evaluation of the combination of the dual m-TORC1/2 inhibitor vistusertib
      (AZD2014) and paclitaxel in ovarian cancer models.
AB  - Activation of the PI3K/mTOR pathway has been shown to be correlated with
      resistance to chemotherapy in ovarian cancer. We aimed to investigate the effects
      of combining inhibition of mTORC1 and 2 using the mTOR kinase inhibitor
      vistusertib (AZD2014) with paclitaxel in in vitro and in vivo ovarian cancer
      models. The combination of vistusertib and paclitaxel on cell growth was additive
      in a majority of cell lines in the panel (n = 12) studied. A cisplatin- resistant
      model (A2780Cis) was studied in vitro and in vivo. We demonstrated inhibition of
      mTORC1 and mTORC2 by vistusertib and the combination by showing reduction in p-S6
      and p-AKT levels, respectively. In the A2780CisR xenograft model compared to
      control, there was a significant reduction in tumor volumes (p = 0.03) caused by
      the combination and not paclitaxel or vistusertib alone. In vivo, we observed a
      significant increase in apoptosis (cleaved PARP measured by immunohistochemistry;
      p = 0.0003). Decreases in phospholipid and bioenergetic metabolites were studied
      using magnetic resonance spectroscopy and significant changes in phosphocholine
      (p = 0.01), and ATP (p = 0.04) were seen in tumors treated with the combination
      when compared to vehicle-control. Based on this data, a clinical trial evaluating
      the combination of paclitaxel and vistusertib has been initiated (NCT02193633).
      Interestingly, treatment of ovarian cancer patients with paclitaxel caused an
      increase in p-AKT levels in platelet-rich plasma and it was possible to abrogate
      this increase with the co-treatment with vistusertib in 4/5 patients: we believe
      this combination will benefit patients with ovarian cancer.

PMID- 29371952
TI  - Truncated protein tyrosine phosphatase receptor type O suppresses AKT signaling
      through IQ motif containing GTPase activating protein 1 and confers sensitivity
      to bortezomib in multiple myeloma.
AB  - Proteasome inhibitors are an important part of our chemotherapeutic armamentarium
      against multiple myeloma, but the vast majority of patients eventually develop
      drug-resistant disease through incompletely understood mechanisms. Comparison of
      gene expression profiles (GEPs) of bortezomib-resistant (BR) myeloma cell lines
      with their drug-naive counterparts revealed decreased expression of truncated
      Protein tyrosine phosphatase receptor-type O (PTPROt) in BR cells. Over
      expression of wild-type PTPROt in drug-naive and BR cells reduced myeloma cell
      proliferation, induced apoptosis, and sensitized cells to bortezomib and to
      alkylating agents. PTPROt expression reduced AKT phosphorylation and activity,
      and sensitized to pharmacologic AKT pathway inhibitors, but this was not the case
      for a substrate-trapping catalytic domain-inactivating mutant. Co
      immunoprecipitation and mass spectrometry studies identified IQ motif containing
      GTPase activating protein 1 (IQGAP1) as a PTPROt binding partner, and PTPROt
      reduced tyrosine phosphorylation of IQGAP1, providing a link to AKT activity.
      Analysis of clinically annotated GEP databases identified high PTPROt expression
      as being related to an increased likelihood of achieving complete remission with
      bortezomib therapy, while low expression was linked to a greater likelihood of
      disease progression. Finally, high PTPROt expression associated with prolonged
      median overall survival in patients receiving bortezomib-based therapy in the
      front-line or relapsed and/or refractory settings. Taken together, these data
      identify PTPROt suppression as a novel mechanism of myeloma resistance to
      bortezomib in myeloma cell lines, and also support the possibility that PTPROt
      expression could be used as a biomarker to predict outcomes with bortezomib, and
      by which to select patients for therapy with AKT inhibitors.

PMID- 29371954
TI  - Integrated hepatic transcriptional and serum metabolic studies on circulating
      nutrient metabolism in diurnal laying hens.
AB  - The aim of the study was to see the diurnal variation of nutrients metabolism and
      their regulation under the management of large-scaled production. The hepatic
      transcriptional and serum metabolic studies on circulating nutrient metabolism
      were investigated in diurnal laying hens. Liver and blood were collected from 36
      hens that were slaughtered at 3:30, 7:30, 11:30, 15:30, 19:30, and 23:30 (n = 6),
      respectively. The serum amino acid, fatty acid and glucose levels, as well as the
      hepatic transcriptome were analyzed. The results revealed that the circadian
      clock genes such as Bmal1, Clock, Per1, and Cry2 displayed circadian rhythms in
      hen livers. The genes related to circulating nutrient transportation,
      lipogenesis, lipid catabolism, sterol metabolism, and oxidative/anti-oxidative
      systems also oscillated. However, the nadir of glucose was observed at 7:30 and
      peaked at 11:30 in the day. Amino acid levels peaked mainly at night, and most
      amino acids exhibited circadian rhythms based on CircWave analysis. With the
      exception of undecanoic acid (C11:0), myristoleic acid (C14:1), cis-11, 14
      eicosenoic acid (C20:2), and (cis-4, 7, 10, 13, 16, 19-docosahexaenoic acid)
      C20:3N6 fatty acids, others peaked at 7:30 and 15:30. The results indicated that
      the hens required more glucose in the early morning. More proteins should be
      ingested late in the day, since protein catabolism occurred mostly at night. To
      remove the redundant fats and lipids, fewer should be ingested, especially during
      the night. All these results would help to design a more accurate nutrition
      schedule for improving the performance of laying hens in the future.

PMID- 29371955
TI  - A comparative global phosphoproteomics analysis of obinutuzumab (GA101) versus
      rituximab (RTX) against RTX sensitive and resistant Burkitt lymphoma (BL)
      demonstrates differential phosphorylation of signaling pathway proteins after
      treatment.
AB  - We recently demonstrated that obinutuzumab (GA101), a novel glycoengineered type
      II CD20 Ab compared to rituximab (RTX) mediates significantly enhanced antibody
      dependent cell cytotoxicity (ADCC) in vitro and increased overall survival in a
      Burkitt lymphoma (BL) xenograft non-obese diabetic severe combined
      immunodeficiency gamma (NSG) model. In this study we compared the
      phosphoproteomic changes by pathway analysis following obinutuzumab vs RTX
      against RTX-sensitive (Raji) and -resistant BL (Raji4RH). Phosphoproteomic
      analyses were performed by mass-spectrometry (MS)-based label-free quantitative
      phosphoproteomic profiling. We demonstrated that 418 proteins in Raji and 377
      proteins in Raji 4RH, were differentially phosphorylated (>1.5-fold) after
      obinutuzumab vs. RTX. Proteins that were significantly differentially
      phosphorylated included the B cell antigen receptor (BCR) (PLCG2, BTK and GSK3B),
      Fc gamma phagocytosis (FCRG2B, MAPK1, PLCG2 and RAF1), and natural killer cell
      mediated cytotoxicity (MAPK1, RAF1, PLCG2 and MAPK3) signaling pathways.
      Differential phosphorylation of BCR or cytotoxicity pathway proteins revealed
      significant up-regulation of BTK, PLCY2 and ERK1/RAF1 after obinutuzumab compared
      to RTX. Silencing of PLCG2 in the BCR and MAPK1 in the cytotoxicity pathway
      significantly increased BL proliferation and decreased BL cytotoxicity after
      obinutuzumab compared to RTX. These results in combination with our previous
      results demonstrating a significant improvement in in vitro BL cytotoxicity and
      in vivo BL survival by obinutuzumab compared to RTX may in part be due to
      differential effects on selected BL protein signaling pathways.

PMID- 29371956
TI  - Canine distemper viral infection threatens the giant panda population in China.
AB  - We evaluated exposure to canine distemper virus (CDV) in eight wild giant pandas
      (Ailuropoda melanoleuca) and 125 unvaccinated domestic dogs living in and around
      Foping National Nature Reserve (FNNR), China. Seventy-two percent of unvaccinated
      domestic dogs (mixed breed) had neutralizing antibodies for CDV due to exposure
      to the disease. The eight wild giant pandas were naive to CDV and carried no
      positive antibody titer. RT-PCR assays for hemagglutinin (H) gene confirmed the
      presence of CDV in 31 clinically ill dogs from several areas near FNNR. Genomic
      sequence analysis showed that the 21 canine CDV were highly homologous to each
      other and belonged to the Asian-1 genotype. They showed high homology with the
      GP01 strain sequenced from a fatally infected giant panda, suggesting cross
      species infection. Observational and GPS tracking data revealed home range
      overlap in pandas and dogs around FNNR. This study shows that CDV is endemic in
      domestic dogs near FNNR and that cross-species CDV infection threatens the wild
      giant panda population.

PMID- 29371957
TI  - Anti-Mullerian hormone levels in patients with gestational trophoblastic
      neoplasia treated with different chemotherapy regimens: a prospective cohort
      study.
AB  - Purpose: To assess the ovarian reserve of patients with gestational trophoblastic
      neoplasia (GTN) treated with chemotherapy by evaluating serum anti-Mullerian
      hormone (AMH) and follicle-stimulating hormone (FSH) levels before, during, and
      after chemotherapy. Results: The basal AMH level (mean: 3.98 +/- 3.20 ng/mL)
      negatively correlated with age, while the basal FSH level (mean: 5.71 +/- 9.69
      mIU/mL) had no correlation with age. After 3 chemotherapy cycles, serum AMH
      levels decreased and FSH levels increased. The magnitude of the AMH level decline
      was significantly greater for combination chemotherapy than for single-agent
      dactinomycin D therapy (61.80% vs. 27.57%) (p = 0.0004) and was higher in
      patients whose regimens included etoposide (73.69% vs 40.51%) (p = 0.0359). After
      chemotherapy completion, AMH levels showed a further decline, and cumulative AMH
      concentration change was associated with doses of vincristine (p = 0.009) and
      etoposide (p = 0.032). At the 3-month follow-up, AMH levels significantly
      increased in the dactinomycin D group (p = 0.0067). Materials and Methods: This
      prospective study included 34 patients with GTN. Serum AMH and FSH levels were
      measured before chemotherapy, after the 3rd cycle, and at 2 weeks and 3 months
      after chemotherapy. Cumulative changes of serum AMH levels in patients who
      received different chemotherapy regimens were analyzed. Conclusions: Chemotherapy
      for GTN affects the ovarian reserve, with substantial differences between
      chemotherapy protocols. The results improve our understanding of ovarian toxicity
      and support the use of fertility preservation strategies.

PMID- 29371958
TI  - Gestational diabetes mellitus is associated with decreased adipose and placenta
      peroxisome proliferator-activator receptor gamma expression in a Chinese
      population.
AB  - Peroxisome proliferator-activated receptors gamma (PPARgamma) is a member of
      nuclear receptor superfamily, and studies have demonstrated that dysregulation of
      PPARgamma was associated with gestational diabetes mellitus (GDM), which is one
      of the most common metabolic abnormalities occurring during pregnancy. However,
      the results regarding the associations between PPARgamma and GDM were conflicting
      among different studies. The present study aimed to determine the expression of
      PPARgamma in adipose and placenta from GDM women in a Chinese population and to
      further explore the role of PPARgamma in GDM women. The adipose and placenta
      tissues were isolated from GDM women and healthy pregnant women at term. The mRNA
      and protein expressions of PPARgamma in adipose and placenta tissues were
      determined by qRT-PCR and western blot, respectively. Univariate correlation
      analysis was used to analyze the relationship between PPARgamma expression and
      clinical characteristics of patients. The levels of tryglycerides and HbA1c were
      significantly higher, while the levels of low density lipoprotein (LDL)
      cholesterol, adiponectin and insulin were significantly lower in the GDM women
      than that in the healthy pregnant women. The mRNA and protein expression of
      PPARgamma in both adipose and placenta from GDM women were significantly lower
      than that from healthy pregnant women. PPARgamma mRNA expression in both adipose
      and placenta positively correlated with LDL cholesterol and adiponectin levels,
      and negatively correlated with tryglycerides and glucose levels at 0 h, 1 h and 2
      h of 75 g oral glucose tolerance test. In summary, our results suggest that
      PPARgamma may be a key modulator in the development of GDM, due to the roles of
      PPARgamma in glucose homeostasis and adipose tissue development and function.

PMID- 29371959
TI  - Modulating the metabolism by trimetazidine enhances myoblast differentiation and
      promotes myogenesis in cachectic tumor-bearing c26 mice.
AB  - Trimetazidine (TMZ) is a metabolic reprogramming agent able to partially inhibit
      mitochondrial free fatty acid beta-oxidation while enhancing glucose oxidation.
      Here we have found that the metabolic shift driven by TMZ enhances the myogenic
      potential of skeletal muscle progenitor cells leading to MyoD, Myogenin, Desmin
      and the slow isoforms of troponin C and I over-expression. Moreover, similarly to
      exercise, TMZ stimulates the phosphorylation of the AMP-activated protein kinase
      (AMPK) and up-regulates the peroxisome proliferator-activated receptor gamma
      coactivator 1-alpha (PGC1alpha), both of which are known to enhance the
      mitochondrial biogenesis necessary for myoblast differentiation. TMZ also induces
      autophagy which is required during myoblast differentiation and promotes myoblast
      alignment which allows cell fusion and myofiber formation. Finally, we found that
      intraperitoneally administered TMZ (5mg/kg) is able to stimulate myogenesis in
      vivo both in a mice model of cancer cachexia (C26 mice) and upon cardiotoxin
      damage. Collectively, our work demonstrates that TMZ enhances myoblast
      differentiation and promotes myogenesis, which might contribute recovering stem
      cell blunted regenerative capacity and counteracting muscle wasting, thanks to
      the formation of new myofibers; TMZ is already in use in humans as an anti
      anginal drug and its repositioning might impact significantly on aging and
      regeneration-impaired disorders, including cancer cachexia, as well as have
      implications in regenerative medicine.

PMID- 29371960
TI  - Modulation of inflammation by toll-like receptor 4/nuclear factor-kappa B in
      diarrhea-predominant irritable bowel syndrome.
AB  - In order to investigate the function of toll-like receptor 4/nuclear factor-kappa
      B (TLR4/NF-kappaB) signal pathways in the pathogenesis of diarrhea-predominant
      irritable bowel syndrome (IBS-D), IBS-D animal models were established in wistar
      rats challenged with acute and chronic stresses (29 days). Wistar rats without
      stress-challenged were used as controls. IBS-D models were randomly divided into
      two groups: one was treated with normal saline, another group was treated with
      TLR4/NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC) (50mg/kg/week) for
      continuous four times. Our results demonstrate that continuous stresses can
      induce the characteristic symptoms of IBS-D, including high wet stool rate and
      intestinal flora imbalance. Further examinations of colon tissues show that the
      protein expression levels of TLR4 and NF-kappaB in IBS-D groups are higher than
      that in control group. The secretory levels of interleukin (IL-8), tumor necrosis
      factor alpha (TNFalpha), and myeloid differentiation factor 88 (MyD88) are
      significantly increased in IBS-D group. Administration with PDTC effectively
      downregulates levels of these inflammatory factors. In contrast, interleukin-10
      (IL-10) is in an opposite alteration with lower levels in IBS-D groups and the
      PDTC treatment increases it to the levels as in control group. Moreover,
      inhibition of the TLR4/NF-kappaB by PDTC improves the microstructure of
      intestinal mucosa mainly by increasing the height of villi. Our results suggest
      that TLR4/NF-kappaB signal pathway plays an important role in the modulation of
      inflammatory responses in IBS-D, which might be a therapeutic target for the IBS
      D. All of these findings also provide the evidence concerning an inherent linkage
      between the axis of stress/NF-kappaB/inflammation and IBS-D.

PMID- 29371961
TI  - Knock-in human GDF5 proregion L373R mutation as a mouse model for proximal
      symphalangism.
AB  - Proximal symphalangism (SYM1) is an autosomal dominant disorder, mainly
      characterized by bony fusions of the proximal phalanges of the hands and feet.
      GDF5 and NOG were identified to be responsible for SYM1. We have previously
      reported on a p.Leu373Arg mutation in the GDF5 proregion present in a Chinese
      family with SYM1. Here, we investigated the effects of the GDF-L373R mutation.
      The variant caused proteolysis efficiency of GDF5 increased in ATDC5 cells. The
      variant also caused upregulation of SMAD1/5/8 phosphorylation and increased
      expression of target genes SMURF1, along with COL2A1 and SOX9 which are factors
      associated with chondrosis. Furthermore, we developed a human-relevant SYM1 mouse
      model by making a Gdf5L367R (the orthologous position for L373R in humans) knock
      in mouse. Gdf5L367R/+ and Gdf5L367R/L367R mice displayed stiffness and adhesions
      across the proximal phalanx joint which were in complete accord with SYM1. It was
      also confirmed the joint formation and development was abnormal in Gdf5L367R/+
      and Gdf5L367R/L367R mice, including the failure to develop the primary
      ossification center and be hypertrophic chondrocytes during embryonic
      development. This knock-in mouse model offers a tool for assessing the
      pathogenesis of SYM1 and the function of the GDF5 proregion.

PMID- 29371962
TI  - Overexpression of NR4A1 is associated with tumor recurrence and poor survival in
      non-small-cell lung carcinoma.
AB  - : The expression level and clinical significance of NR4A1 are presently unknown
      in the non-small-cell lung carcinoma (NSCLC). This study aimed to explore the
      expression, prognostic value, and function of NR4A1 in NSCLC. METHODS:
      Clinicopathological parameters of 167 NSCLC patients who received radical surgery
      from January 2007 and December 2012 were retrospectively reviewed. The NR4A1
      expression in NSCLC tumors and the adjacent matched para-carcinoma specimens were
      examined, and the association between NR4A1 expression and clinical variables was
      explored. Cell viability assay, and transwell migration and invasion assays were
      used to access the function of NR4A1 in NSCLC. Kaplan-Meier analysis and Cox
      regression were performed to investigate the prognostic significance of NR4A1 for
      NSCLC. RESULTS: NR4A1 was overexpressed in NSCLC tissues compared with the para
      carcinoma specimens. Consistently, Oncomine analysis showed that NR4A1 was
      overexpressed in NSCLC tissues compared with normal tissues in published datasets
      (P < 0.001). The elevated NR4A1 expression was associated with carcinoma
      recurrence (P < 0.05). The 5-year median overall survival (OS) and progression
      free survival (PFS) were significantly poorer in the NR4A1-overexpression group.
      Multivariate Cox analysis showed that NR4A1 overexpression was an independent
      factor for OS (HR, 95%CI: P < 0.05) and PFS (HR, 95%CI: P < 0.05) in NSCLC.
      Moreover, knockdown of NR4A1 significantly reduced NSCLC cell proliferation,
      migration, and invasion. CONCLUSIONS: NR4A1 exhibits a tumor-promoting effect on
      NSCLC, and might serve as a promising prognostic biomarker and a therapeutic
      target for NSCLC.

PMID- 29371963
TI  - Genome-wide analysis of the human malaria parasite Plasmodium falciparum
      transcription factor PfNF-YB shows interaction with a CCAAT motif.
AB  - Little is known about transcription factor regulation during the Plasmodium
      falciparum intraerythrocytic cycle. In order to elucidate the role of the P.
      falciparum (Pf)NF-YB transcription factor we searched for target genes in the
      entire genome. PfNF-YB mRNA is highly expressed in late trophozoite and schizont
      stages relative to the ring stage. In order to determine the candidate genes
      bound by PfNF-YB a ChIP-on-chip assay was carried out and 297 genes were
      identified. Ninety nine percent of PfNF-YB binding was to putative promoter
      regions of protein coding genes of which only 16% comprise proteins of known
      function. Interestingly, our data reveal that PfNF-YB binding is not exclusively
      to a canonical CCAAT box motif. PfNF-YB binds to genes coding for proteins
      implicated in a range of different biological functions, such as replication
      protein A large subunit (DNA replication), hypoxanthine phosphoribosyltransferase
      (nucleic acid metabolism) and multidrug resistance protein 2 (intracellular
      transport).

PMID- 29371964
TI  - Factor inhibiting HIF1-A novel target of SUMOylation in the human placenta.
AB  - Adaptations to changes in oxygen are critical to ensure proper placental
      development, and impairments in oxygen sensing mechanisms characterize placental
      pathologies such as preeclampsia. In this study, we examined the involvement of
      SUMOylation, a reversible posttranslational modification, in the regulation of
      the asparaginyl hydroxylase Factor Inhibiting Hypoxia Inducible Factor 1 (FIH1)
      in the human placenta in development and in disease status. FIH1 protein
      abundance and spatial distribution in the developing placenta directly correlated
      with oxygen tension in vivo. Immunofluorescence analysis showed that early on
      FIH1 primarily localized to nuclei of cytotrophoblast cells, while after 10 weeks
      of gestation it was present in nuclei and cytoplasm of both cytotrophoblast and
      syncytiotrophoblast cells. Exposure of choriocarcinoma JEG-3 cells to hypoxia
      induced FIH1 SUMOylation by promoting its association to SUMO2/3. Transfection of
      JEG-3 cells with FIH1 constructs containing SUMO-mutated sites revealed that
      SUMOylation of FIH1 by SUMO2/3 targeted it for proteasomal degradation,
      particularly in hypoxia. SUMOylation of FIH1 directly impacted on HIF1A activity
      as determined by HIF-responsive luciferase assay. Co-immunoprecipitation analyses
      revealed enhanced FIH1-SUMO2/3 associations early in development, when FIH1
      levels are low, while deSUMOylation of FIH1 by SENP3 increased later in
      gestation, when FIH1 levels are rising. In preeclampsia, decreased FIH1 protein
      expression associated with impaired deSUMOylation by SENP3 and increased
      association with the ubiquitin ligase RNF4. We propose a novel mode of regulation
      of FIH1 stability by dynamic SUMOylation and deSUMOylation in the human placenta
      in response to changing oxygen tension, thereby mediating HIF1A transcriptional
      activity in physiological and pathological conditions.

PMID- 29371965
TI  - A link between RelB expression and tumor progression in laryngeal cancer.
AB  - Laryngeal cancer is a frequent malignancy originating from the squamous vocal
      epithelium in a multi-stage fashion in response to environmental carcinogens.
      Although most cases can be cured by surgery and/or radiotherapy, advanced and
      relapsing disease is common, and biomarkers of such dismal cases are urgently
      needed. The cancer genome of laryngeal cancers was recently shown to feature a
      signature of aberrant nuclear factor (NF)-kappaB activation, but this finding has
      not been clinically exploited. We analyzed primary tumor samples of 96 well
      documented and longitudinally followed patients covering the whole spectrum of
      laryngeal neoplasia, including 21 patients with benign laryngeal diseases, 15
      patients with dysplasia, 43 patients with early-stage carcinoma, and 17 patients
      with locally advanced carcinoma, for immunoreactivity of RelA, RelB, P50, and
      P52/P100, the main NF-kappaB subunits that activate transcription. Results were
      cross-examined with indices of tumor progression and survival. Interestingly,
      RelB expression increased with tumor stage, grade, and local extent. Moreover,
      patients displaying high RelB immunoreactivity exhibited statistically
      significantly poorer survival compared with patients featuring low levels of RelB
      expression (P = 0.018 by log-rank test). Using Cox regression analyses and tumor
      stage, local extent, grade and RelA/RelB immunoreactivity, we develop a new score
      that can independently predict survival of patients with laryngeal cancer. Hence
      we provide a simple and affordable NF-kappaB-based test to predict prognosis in
      laryngeal cancer.

PMID- 29371966
TI  - Highly preserved consensus gene modules in human papilloma virus 16 positive
      cervical cancer and head and neck cancers.
AB  - In this study, we investigated the consensus gene modules in head and neck cancer
      (HNC) and cervical cancer (CC). We used a publicly available gene expression
      dataset, GSE6791, which included 42 HNC, 14 normal head and neck, 20 CC and 8
      normal cervical tissue samples. To exclude bias because of different human
      papilloma virus (HPV) types, we analyzed HPV16-positive samples only. We
      identified 3824 genes common to HNC and CC samples. Among these, 977 genes showed
      high connectivity and were used to construct consensus modules. We demonstrated
      eight consensus gene modules for HNC and CC using the dissimilarity measure and
      average linkage hierarchical clustering methods. These consensus modules included
      genes with significant biological functions, including ATP binding and
      extracellular exosome. Eigengen network analysis revealed the consensus modules
      were highly preserved with high connectivity. These findings demonstrate that
      HPV16-positive head and neck and cervical cancers share highly preserved
      consensus gene modules with common potentially therapeutic targets.

PMID- 29371967
TI  - Prognostic values of long non-coding RNA MIR22HG for patients with hepatocellular
      carcinoma after hepatectomy.
AB  - Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer
      worldwide and the second most frequent cause of cancer death. The aim of this
      study is to identify the association between the expression of long non-coding
      RNA (lncRNA) MIR22HG and the clinical and tumor characteristics of patients with
      HCC, and to explore the prognostic significance of lncRNA MIR22HG on patients
      with HCC. We retrospectively reviewed 127 patients with HCC(42 female, 85 male)
      who were managed in our hospital between May 1st 2010 and June 30th 2016. The
      expressions of lncRNA MIR22HG were detected by real-time PCR. Prognostic factors
      were evaluated using Kaplan-Meier curves and Cox proportional hazards models. For
      the entire cohort of 127 patients, the normalized real-time PCR showed that the
      expression of lncRNA MIR22HG was lower in HCC tissues compared with corresponding
      nontumorous tissues. MTT assay showed that si-MIR22HG remarkably inhibited the
      proliferation tumor cells in three HCC cell lines including SMMC-7721, Huh-7 and
      Hep3B. Moreover, under-expression of MIR22HG was closely related to tumor
      encapsulation, microvascular invasion (MVI), and TNM stage. Cox proportional
      hazards analysis demonstrated that lncRNA MIR22HG under-expression was an
      independent risk factor associated with the prognosis of patients with HCC. In
      conclusion, we found that lncRNA MIR22HG expressed significantly lower in HCC
      tissues compared with non-tumorous tissues. Under-expression of lncRNAMIR22HG was
      an independent risk factor associated with the prognosis of patients with HCC.

PMID- 29371968
TI  - AMRI-59 functions as a radiosensitizer via peroxiredoxin I-targeted ROS
      accumulation and apoptotic cell death induction.
AB  - Previously, we identified AMRI-59 as a specific pharmaceutical inhibitor of
      peroxiredoxin (PRX) I enzyme activity. In this study, we examined whether AMRI-59
      acts as a radiosensitizer in non-small cell lung cancer cells using clonogenic
      assays. The intracellular mechanisms underlying the radiosensitization effect of
      AMRI-59 were determined via immunoblotting in addition to measurement of ROS
      generation, mitochondrial potential and cell death. AMRI-59 activity in vivo was
      examined by co-treating nude mice with the compound and gamma-ionizing radiation
      (IR), followed by measurement of tumor volumes and apoptosis. The dose
      enhancement ratios of 30 MUM AMRI-59 in NCI-H460 and NCI-H1299 were 1.51 and
      2.12, respectively. Combination of AMRI-59 with IR augmented ROS production and
      mitochondrial potential disruption via enhancement of PRX I oxidation, leading to
      increased expression of gammaH2AX, a DNA damage marker, and suppression of ERK
      phosphorylation, and finally, activation of caspase-3. Notably, inhibition of ROS
      production prevented ERK suppression, and blockage of ERK in combination with
      AMRI-59 and IR led to enhanced caspase-3 activation and apoptosis. In a xenograft
      assay using NCI-H460 and NCI-H1299, combined treatment with AMRI-59 and IR
      delayed tumor growth by 26.98 and 14.88 days, compared with controls, yielding
      enhancement factors of 1.73 and 1.37, respectively. Taken together, the results
      indicate that AMRI-59 functions as a PRX I-targeted radiosensitizer by inducing
      apoptosis through activation of the ROS/gammaH2AX/caspase pathway and suppression
      of ERK.

PMID- 29371969
TI  - MiR-124 acts as a target for Alzheimer's disease by regulating BACE1.
AB  - Although large numbers of microRNAs (miRNAs) expressed in Alzheimer disease (AD)
      have been detected, their functions and mechanisms of regulation remain to be
      fully clarified. Beta-site Amyloid precursor protein Cleaving Enzyme 1 (BACE1)
      has been one of the prime therapeutic targets for AD. Here, we identified that
      miR-124 levels are gradually decreased in AD. In addition, we demonstrated that
      miR-124 suppresses BACE1 expression by directly targeting the 3'UTR of Bace1 mRNA
      in vitro. Inhibition of miR-124 significantly increased BACE1 levels in neuronal
      cells. In contrast, miR-124 overexpression significantly suppressed BACE1
      expression in cells. And finally we determined that downregulation of miR-124
      alleviated Abeta-induced viability inhibition and decreased apoptosis in SH-SY5Y
      cells. Our results demonstrated that miR-124 is a potent negative regulator of
      BACE1 in the cellular AD phenotype and might be involved in the pathogenesis of
      AD.

PMID- 29371970
TI  - MicroRNA miR-147b promotes tumor growth via targeting UBE2N in hepatocellular
      carcinoma.
AB  - As the subfamily of noncoding RNA, microRNAs (miRNAs) broadly regulate the
      development of cancers, while their dysregulation and function in human
      hepatocellular carcinoma (HCC) remains largely unclear. Here, we found the
      expression level of microRNA-147b (miR-147b) is increased aberrantly in HCC tumor
      tissues, and its expression positively correlates to the tumor severity. In both
      MTT and colony formation assay, knockdown of miR-147b dramatically inhibits in
      vitro proliferation of HCC cell lines. More interestingly, we also performed in
      vivo tumorigenesis assay and found that miR-147b can regulate in vivo
      tumorigenesis in nude mice xenograft models. The ubiquitin-conjugating enzyme E2N
      (UBE2N) was identified directly and functionally targeted by miR-147b. The mRNA
      level of UBE2N is increased in HCC tumors or cell lines. Restoring UBE2N
      expression level in tumor cells leads to inhibition of cell proliferation, which
      mimics the effect upon miR-147b knockdown in the same cells. These data
      elucidated the oncogenic role of miR-147b in HCC development and progression with
      therapeutic target potentials.

PMID- 29371971
TI  - Association between the PINX1 and NAT2 polymorphisms and serum lipid levels.
AB  - Jing nationality is a relatively conservative and isolated minority in China.
      Little is known about the association of the PIN2/TERF1-interacting telomerase
      inhibitor 1 (PINX1) and N-acetyltransferase 2 (NAT2) single nucleotide
      polymorphisms (SNPs) and serum lipid levels in the Chinese populations. This
      study aimed to clarify the association of 6 SNPs of the PINX1 and NAT2 and serum
      lipid levels in two Chinese populations. Genotyping of the SNPs was performed in
      1236 Han subjects and 1248 Jing participants. Allelic and genotypic frequencies
      of these variants (except NAT2 rs1799931) were different between the two ethnic
      groups. The minor allele carriers had higher triglyceride (TG, rs11776767,
      rs1495743 and rs1799930), low-density lipoprotein cholesterol (rs6601530) levels
      and the apolipoprotein (Apo)A1/ApoB ratio (rs1495743) in Han nationality; and
      higher total cholesterol (rs1961456), TG (rs11776767, rs6601530 and rs1495743)
      and lower ApoA1 (rs6601530 and rs1799931) levels in Jing minority than the minor
      allele non-carriers. The SNPs were not statistically independent by the multiple
      locus linkage disequilibrium analyses. The integrative haplotypes and gene-by
      gene (G * G) interactions on serum lipid traits were also observed in the two
      populations. Association analysis based on haplotypes and G * G interactions
      might be powerful than single-locus tests. Differences in serum lipid profiles
      between the two populations might partially be attributed to these SNPs, their
      haplotypes and G * G interactions.

PMID- 29371972
TI  - CD44 drives aggressiveness and chemoresistance of a metastatic human osteosarcoma
      xenograft model.
AB  - Background: Osteosarcoma is the most common primary malignant bone tumor with a 5
      year survival rate of up to 70%. However, patients with metastatic disease have
      still a very poor prognosis. Osteosarcoma metastasis models are essential to
      develop novel treatment strategies for advanced disease. Methods: Based on a
      serial transplantation approach, we have established a U-2 OS osteosarcoma
      xenograft model with increased metastatic potential and compared it to other
      metastatic osteosarcoma models from international sources. Subclones with
      differing invasive potential were compared for genomic gains and losses as well
      as gene expression changes by several bioinformatic approaches. Based on the
      acquired results, the effects of a shRNA-mediated CD44 mRNA knockdown on
      migration, invasion and chemosensitivity were evaluated. Results: The CD44 gene
      was part of an amplified region at chromosome 11p found in both U-2 OS subclones
      with enhanced metastatic potential but not in parental U-2 OS cells,
      corresponding with distinct CD44 overexpression. Accordingly, shRNA-mediated CD44
      knockdown significantly attenuated osteosarcoma cell migration, invasion, and
      viability especially in the metastatic subclones of U-2 OS and Saos-2 cells.
      Metastatic subclones generally were hypersensitive against the integrin inhibitor
      cilengitide paralleled by alterations in integrin expression pattern following
      CD44 knock-down. Additionally, attenuation of CD44 expression sensitized these
      cell models against osteosarcoma chemotherapy with doxorubicin but not
      methotrexate and cisplatin. Conclusions: The osteosarcoma xenograft models with
      increased metastatic potential developed in this study can be useful for
      identification of mechanisms driving metastasis and resistance towards clinically
      used and novel therapeutic regimens.

PMID- 29371973
TI  - 17-beta-Estradiol induces spreading depression and pain behavior in alert female
      rats.
AB  - Aims: Test the putative contribution of 17-beta-estradiol in the development of
      spreading depression (SD) events and head pain in awake, non-restrained rats.
      Main Methods: Female, Sprague-Dawley rats were intact or underwent ovariectomy
      followed one week later by surgery to place electrodes onto the dura to detect
      epidural electroencephalographic activity (dEEG). dEEG activity was recorded two
      days later for 12 hours after systemic administration of 17-beta-estradiol (180
      MUg/kg, i.p.). A separate set of rats were observed for changes in exploratory,
      ambulatory, fine, and rearing behaviors; periorbital allodynia was also assessed.
      Key Findings: A bolus of 17-beta-estradiol significantly elevated serum estrogen
      levels, increased SD episodes over a 12-hour recording period and decreased
      rearing behaviors in ovariectomized rats. Pre-administration of ICI 182,780, an
      estrogen receptor antagonist, blocked 17-beta-estradiol-evoked SD events and pain
      behaviors; similar results were observed when the antimigraine therapeutic
      sumatriptan was used. Significance: These data indicate that an estrogen receptor
      mediated mechanism contributes to SD events in ovariectomized rats and pain
      behaviors in both ovariectomized -and intact- rats. This suggests that estrogen
      plays a different role in each phenomenon of migraine where intense fluctuations
      in concentration may influence SD susceptibility. This is the first study to
      relate estrogen peaks to SD development and pain behaviors in awake, freely
      moving female rats, establishing a framework for future preclinical migraine
      studies.

PMID- 29371974
TI  - Novel proteasome inhibitor delanzomib sensitizes cervical cancer cells to
      doxorubicin-induced apoptosis via stabilizing tumor suppressor proteins in the
      p53 pathway.
AB  - Cervical cancer, the third most commonly occurring cancer, is the second leading
      cause of cancer related mortality among women. Aberrant ubiquitination and
      proteasome activity, both human papillomavirus and tumor derived, have been shown
      to contribute to tumor angiogenesis, proliferation, and invasion in many cancers,
      including cervical cancer. Thus, small molecule proteasome inhibitors are a
      potential and strategic treatment option for cervical cancer. In this study,
      novel proteasome inhibitor delanzomib (CEP-18770) exhibited potent pro-apoptotic
      and cytotoxic effects on a panel of cervical cancer cell lines by blocking
      proteasomal activity. Delanzomib also significantly sensitized cervical cancer
      cells to treatment of doxorubicin (Dox), a traditional chemotherapeutic agent.
      Furthermore, proteasome inhibition revealed stabilization of p53 and p53
      transcriptional targets and induction of p38/JNK phosphorylation. Additionally,
      delanzomib worked synergistically with Dox to further upregulate p53 and its
      downstream targets and enhanced Dox-induced p38 phosphorylation. Our study
      strongly supports the 26S proteasome as a potential therapeutic target in
      cervical cancer and proteasome inhibition by delanzomib may be a potential
      treatment strategy for cervical cancer patients.

PMID- 29371975
TI  - The role of prospero homeobox 1 (PROX1) expression in follicular thyroid
      carcinoma cells.
AB  - The prospero homeobox 1 (Prox1) transcription factor is a key player during
      embryogenesis and lymphangiogenesis. Altered Prox1 expression has been found in a
      variety of human cancers, including papillary thyroid carcinoma (PTC).
      Interestingly, Prox1 may exert tumor suppressive or tumor promoting effect,
      depending on the tissue context. In this study, we have analyzed Prox1 expression
      in normal and malignant human thyroid carcinoma cell lines. Moreover, we
      determined the effect of Prox1 silencing and overexpression on the cellular
      processes associated with the metastatic potential of tumor cells: proliferation,
      migration, invasion, apoptosis and anchorage-independent growth, in the
      follicular thyroid carcinoma (FTC) FTC-133 cell line. We found that Prox1
      expression was significantly higher in FTC-derived cells than in PTC-derived
      cells and normal thyroid, and it was associated with the PI3K/Akt signaling
      pathway. In the FTC-133 cells, it was associated with cell invasive potential,
      motility and wound closure capacities, but not with proliferation or apoptosis.
      Modifying Prox1 expression also induced substantial changes in the cytoskeleton
      structure and cell morphology. In conclusion, we have shown that Prox1 plays an
      important role in the development of FTC and that its suppression prevents,
      whereas its overexpression promotes, the malignant behavior of thyroid follicular
      cancer cells.

PMID- 29371976
TI  - HDAC inhibition potentiates immunotherapy in triple negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) represents a more aggressive and difficult
      subtype of breast cancer where responses to chemotherapy occur, but toxicity is
      significant and resistance often follows. Immunotherapy has shown promising
      results in various types of cancer, including breast cancer. Here, we
      investigated a new combination strategy where histone deacetylase inhibitors
      (HDACi) are applied with immune checkpoint inhibitors to improve immunotherapy
      responses in TNBC. Testing different epigenetic modifiers, we focused on the
      mechanisms underlying HDACi as priming modulators of immunotherapy. Tumor cells
      were co-cultured with human peripheral blood mononuclear cells (PBMCs) and flow
      cytometric immunophenotyping was performed to define the role of epigenetic
      priming in promoting tumor antigen presentation and immune cell activation. We
      found that HDACi up-regulate PD-L1 mRNA and protein expression in a time
      dependent manner in TNBC cells, but not in hormone responsive cells. Focusing on
      TNBC, HDACi up-regulated PD-L1 and HLA-DR on tumor cells when co-cultured with
      PBMCs and down-regulated CD4+ Foxp3+ Treg in vitro. HDACi significantly enhanced
      the in vivo response to PD-1/CTLA-4 blockade in the triple-negative 4T1 breast
      cancer mouse model, the only currently available experimental system with
      functional resemblance to human TNBC. This resulted in a significant decrease in
      tumor growth and increased survival, associated with increased T cell tumor
      infiltration and a reduction in CD4+ Foxp3+ T cells in the tumor
      microenvironment. Overall, our results suggest a novel role for HDAC inhibition
      in combination with immune checkpoint inhibitors and identify a promising
      therapeutic strategy, supporting its further clinical evaluation for TNBC
      treatment.

PMID- 29371977
TI  - Insulin and novel thioglycosides exert suppressive effect on human breast and
      colon carcinoma cells.
AB  - The rationale for the implementation of novel therapies should be based on
      hallmarks of cancer. Two novel compounds labelled as thioglycoside A and B were
      designed and evaluated on breast and colon cancer cell lines. We assessed their
      cytotoxic effect after sensitizing cancer cells with insulin. In order to explore
      the underlying mechanisms, we performed tests to assess cell migration and
      motility, apoptosis, expression of glucose transporter 1 and proapoptotic
      proteins. Both compounds proved to have an antitumor effect which was
      significantly enhanced in combination with insulin. Linking glucose and
      anticancer agent presents an approach that exploits the Warburg effect. Targeting
      dysfunctional glycometabolism and increased glucose absorption is emerging as a
      promising anticancer strategy.

PMID- 29371978
TI  - Identification and validation of colorectal neoplasia-specific methylation
      biomarkers based on CTCF-binding sites.
AB  - To date, the sensitivity of currently available biomarkers based on the
      methylation of gene promoters is suboptimal for detecting adenomas and early
      stage colorectal cancer (CRC). We aimed to develop biomarkers with methylated DNA
      binding sites of the multifunctional transcriptional factor CTCF for early
      detection of CRC. Using combined analyses of genome-wide occupation and the
      methylation profile of CTCF-binding sites, we identified candidate CTCF-binding
      sites. Then, we applied methylation-sensitive high-resolution melting (MS-HRM)
      and mass spectrometry analysis to screen and validate these candidate sites in
      diverse sample sets. We identified a set of colorectal neoplasia-specific
      biomarkers with robust performance. The top five biomarkers were selected and
      recommended for early detection of colorectal neoplasia. All of the five novel
      biomarkers exhibited a more robust discriminatory performance than that by BMP3
      and NDRG4, two currently acknowledged robust methylation biomarkers. When the
      five new biomarkers were considered as a marker panel and tumor-positive was
      defined as having two or more (of the five) positive biomarkers, the marker panel
      could achieve a sensitivity of 91.67% for adenomas, 97.44% for Stage I CRC,
      94.06% for Stage II CRC, 93.62% for Stage III CRC, and 93.54% for total
      colorectal tumors with a specificity of 94.05%. To our knowledge, this is the
      first study for colorectal neoplasia-specific methylation biomarkers based on
      CTCF-binding sites. Using a similar strategy, CTCF-binding sites could be
      potentially developed into biomarkers for other tumors. In summary, this study
      opens a new area in developing biomarkers for tumor prevention and treatment.

PMID- 29371979
TI  - ETV4 collaborates with Wnt/beta-catenin signaling to alter cell cycle activity
      and promote tumor aggressiveness in gastrointestinal stromal tumor.
AB  - Gastrointestinal stromal tumor (GIST) is the most common sarcoma, often resulting
      from a KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation.
      The lineage transcription factor ETV1 is expressed similarly in GISTs regardless
      of malignant potential. Although the related transcription factor ETV4 has been
      associated with metastasis and tumor progression in other cancers, its role in
      GIST is unknown. In this study, we found that ETV4 levels were high in a subset
      of human GISTs and correlated with high mitotic rate. Through Gene Set Enrichment
      Analysis in selected human GISTs, we identified a relationship between ETV4
      levels and beta-catenin signaling, especially in advanced GISTs. GIST specimens
      with high ETV4 levels overexpressed cell cycle regulating genes and had aberrant
      activation of the canonical Wnt pathway. In human GIST cell lines, ETV4 RNA
      interference suppressed cell cycle genes and Wnt/beta-catenin signaling. ETV4
      knockdown also reduced tumor cell proliferation, invasion, and tumor growth in
      vivo. Conversely, ETV4 overexpression increased cyclin D1 expression and Wnt/beta
      catenin signaling. Moreover, we determined that ETV4 knockdown destabilized
      nuclear beta-catenin and increased its degradation via COP1, an E3 ligase
      involved in both ETV4 and beta-catenin turnover. Aberrant accumulation of ETV4
      and nuclear beta-catenin was found in patient derived xenografts created from
      metastatic GISTs that became resistant to tyrosine kinase inhibitors.
      Collectively, our findings highlight the significance of ETV4 expression in GIST
      and identify ETV4 as a biomarker in human GISTs.

PMID- 29371981
TI  - Suppressor of fused (Sufu) promotes epithelial-mesenchymal transition (EMT) in
      cervical squamous cell carcinoma.
AB  - Suppressor of fused is essential for the maximal activation of Sonic Hedgehog
      signaling in development and tumorigenesis. However, the role of Sufu in cervical
      carcinoma remains unknown. Here, we report new findings of Sufu in regulating the
      epithelial-to-mesenchymal transition through the FoxM1 transcriptional modulation
      by 14-3-3zeta protein in cervical carcinoma. Sufu is overexpressed in cervical
      squamous cell carcinoma and its level in clinical tumor tissues is positively
      correlated with 14-3-3zeta. Functionanlly, siSufu remarkably prevents the cancer
      cell migration and invasion. We further demonstrate that the transcriptional
      activity of Sufu is increased by FoxM1, of which stability is promoted by 14-3
      3zeta. Knockdown FoxM1 decreases the invasion of SiHa cells and reconstitution of
      Sufu rescues the invasion of these cells.Finally, overexpression of Sufu is
      significantly associated with differentiation grade, FIGO stage, Depth of stromal
      invasion and vascular cancer embolus. Our findings highlight a novel role for
      Sufu in cervical carcinogenesis.

PMID- 29371980
TI  - Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined
      with radiotherapy.
AB  - High-grade neuroepithelial tumor of the central nervous system with BCOR
      alteration (HGNET-BCOR) is a rare, highly malignant tumor. At the time of this
      publication, no standard protocol exists to treat this tumor entity. In this
      work, we tested the responsiveness of the primary culture PhKh1 derived from
      tumor tissue from a pediatric HGNET-BCOR patient (P1) to inhibitors of the Sonic
      hedgehog pathway combined with radiation. The SMO inhibitors vismodegib and
      itraconazole had low effect on the proliferation of the PhKh1 cells. However, the
      GLI inhibitor arsenic trioxide reduced the expression of GLI target genes in the
      PhKh1 cells and in combination with radiotherapy significantly decreased their
      clonogenic potential. PhKh1 cells resistant to arsenic trioxide were
      characterized by the overexpression of molecular chaperones. We combined arsenic
      trioxide and radiation in the relapse therapy protocol of P1, achieving complete
      remission after seven weeks. Clinical remission lasted for six months, when P1
      developed systemic metastases. Meanwhile, an increase in the concentration of
      circulating tumor DNA carrying a BCOR internal tandem duplication was observed.
      Molecular characterization of a second patient (P2) was also performed. In P2, we
      detected a larger tandem duplication and greater activation of the Sonic hedgehog
      pathway than in P1. These findings suggest that combining arsenic trioxide with
      radiotherapy may represent a new therapeutic approach. Moreover, peripheral blood
      analysis for circulating tumor DNA could help in the early detection of systemic
      metastases.

PMID- 29371982
TI  - Biomarkers identification by a combined clinical and metabonomics analysis in
      Henoch-Schonlein purpura nephritis children.
AB  - Background: In children with Henoch-Schonlein purpura (HSP), the severity of
      Henoch-Schonlein purpura nephritis (HSPN) is considered responsible for the
      prognosis of HSP. The pathological process from HSP to HSPN is not clear yet and
      current diagnostic tools have shortcomings in accurate diagnosis of HSPN. This
      study aims to assess clinical characteristics of HSP and HSPN, to identify
      metabolic perturbations involved in HSP progress, and to combine metabolic
      biomarkers and clinical features into a better prediction for HSPN. Methods: A
      total of 162 children were recruited, including 109 HSP patients and 53 healthy
      children (HC). The clinical characteristics were compared between HSPN and HSP
      without nephritis (HSPWN). The serum metabonomics analysis was performed to
      determine the metabolic differences in HSP and HC. Results: Among 109 HSP
      children, 57 progressed to HSPN. The increased D-dimer level was significantly
      associated with renal damage in HSP. The metabonomic profiles revealed
      alterations between various subgroups of HSP and HC, making it possible to
      investigate small-molecule metabolites related to the pathological process of
      HSP. In total, we identified 9 biomarkers for HSP vs. HC, 7 for HSPWN vs. HC, 9
      for HSPN vs. HC, and 3 for HSPN vs. HSPWN. Conclusions: (S)-3-hydroxyisobutyric
      acid, p-Cresol sulfate, and 3-carboxy-4-methyl-5-pentyl-2-furanpropanoic acid
      were found associated with the progress of HSP to HSPN. Moreover, resulting
      biomarkers, when combined with D-dimer, allowed improving the HSPN prediction
      with high sensitivity (94.7%) and specificity (80.8%). Together these findings
      highlighted the strength of the combination of metabonomics and clinical analysis
      in the research of HSP.

PMID- 29371983
TI  - Augmentation of hypoxia-inducible factor-1-alpha in reinfused blood cells
      enhances diabetic ischemic wound closure in mice.
AB  - Diabetes-associated dysfunction in angiogenesis predominantly contributes to
      impairment of wound closure, but a role of hypoxia-inducible factor 1 alpha (HIF
      1a) in the process remain poorly understood. Here, we examined whether expression
      of HIF-1a in re-infused blood cells may improve the diabetic wound closure in
      mice. We found that that expression of HIF-1a in re-infused isogeneic blood cells
      significantly improved diabetic wound healing in mice, seemingly through
      augmentation of wound-associated angiogenesis. Mechanistically, expression of HIF
      1a in re-infused blood cells significantly increased macrophage infiltration at
      the wound site, and macrophages produced vascular endothelial growth factor A
      (VEGF-A) to promote wound-associated angiogenesis. Together, our data suggest
      that augmentation of HIF-1a in reinfused blood cells may enhance diabetic
      ischemic wound closure.

PMID- 29371984
TI  - Clinical significances and features of prompt brain CT scan after intracranial
      artery stenting: analysis of 501 cases.
AB  - Cerebral hemorrhage is a serious complication of intracranial artery stenting
      that could be fatal without timely identification and treatment. Prompt brain CT
      scan would help to evaluate whether cerebral hemorrhage occurs, however, the
      diverse features of the CT scan immediately after stenting could influence the
      judgement sometimes. Therefore, we analyzed and summarized these features to help
      to determine the clinical significance of these CT features. The prompt CT
      features after stenting were classified into three types. Type I indicates that
      no high-density shadows. Type II indicates that high-density shadows scattered in
      the infarct areas and/or subarachnoid spaces without mass effect. Type III
      indicates high-density shadows scattered in and/or out of the infarct areas
      and/or subarachnoid space with obvious mass effects. Based on this
      classification, the patients in both Type I and II would continue the double anti
      platelet treatment (DAPT) and anti-coagulation treatment, while the later need
      closer monitoring. However, patients in Type III must immediately withdraw the
      DAPT and anti-coagulation treatment with close monitoring and surgical
      intervention was needed when necessary. Nineteen (3.79%) patients were classified
      into Type III, and 5 (1.00%) of the 19 were accepted surgical intervention. Two
      of these patients died (0.40%). The prompt CT scan timely distinguishing the
      cerebral hemorrhage was necessary after intracranial artery stent angioplasty.
      Additionally, based on the different prompt CT features to take different
      therapeutic strategies after stenting would achieve better outcomes for ischemic
      stroke or transient ischemic stroke (TIA) patients underwent intracranial artery
      endovascular therapy.

PMID- 29371985
TI  - Relationships between lymphocyte counts and treatment-related toxicities and
      clinical responses in patients with solid tumors treated with PD-1 checkpoint
      inhibitors.
AB  - The relationships between absolute lymphocyte counts (ALC), drug- related
      toxicities, and clinical responses remain unclear in cancer patients treated with
      PD-1 (programmed cell death 1) inhibitors. We performed a retrospective review of
      167 adult solid tumor patients treated with nivolumab or pembrolizumab at a
      single institution between January 2015 and November 2016. Patients with an ALC
      >2000 at baseline had an increased risk of irAE (OR 1.996, p<0.05) on
      multivariate analysis. In a multivariate proportional hazards model, a shorter
      time to progression was noted in patients who were lymphopenic at baseline (HR
      1.45 (p<0.05)) and at three months (HR 2.01 (p<0.05)). Patients with baseline
      lymphopenia and persistent lymphopenia at month 3 had a shorter time to
      progression compared to those who had baseline lymphopenia but recovered with ALC
      > 1000 at 3 months (HR 2.76, p<0.05). Prior radiation therapy was the
      characteristic most strongly associated with lymphopenia at 3 months (OR 2.24,
      p<0.001). These data suggest that patients with higher baseline lymphocyte counts
      have a greater risk for irAE, whereas patients with lymphopenia at baseline and
      persistent lymphopenia while on therapy have a shorter time to progression on
      these agents. These associations require further validation in additional patient
      cohorts.

PMID- 29371986
TI  - MicroRNA-424/E2F6 feedback loop modulates cell invasion, migration and EMT in
      endometrial carcinoma.
AB  - Our previous study explored the roles of microRNA-424 (miR-424) in the
      development of endometrial carcinoma (EC) and analyzed the miR-424/E2F7 axis in
      EC cell growth. In this study, we investigated the status of miR-424 in human
      endometrial cancer tissues, which were collected from a cohort of Zunyi patients.
      We found that the expression level of miR-424 was associated with clinical tumor
      stage, cell differentiation, lymph node metastasis and cell migration ability.
      Cell function experiments demonstrated that miR-424 overexpression suppressed the
      invasion and migration abilities of endometrial carcinoma cells in vitro.
      Bioinformatic predictions and dual-luciferase reporter assays suggested E2F6 as a
      possible target of miR-424. RT-PCR and western blot assays demonstrated that miR
      424 transfection reduced the expression level of E2F6, while inhibiting miR-424
      with ASO-miR-424 (antisense oligonucleotides of miR-424) increased the expression
      level of E2F6. Cell function experiments indicated that E2F6 transfection rescued
      the EC cell phenotype induced by miR-424. In addition, we also found that E2F6
      negatively regulated miR-424 expression in EC cells. In summary, our results
      demonstrated that the miR-424/E2F6 feedback loop modulates cell invasion,
      migration and EMT in EC and that the miR-424/E2Fs regulation network may serve as
      a new and potentially important therapeutic target in EC.

PMID- 29371987
TI  - Sequentially administrated of pemetrexed with icotinib/erlotinib in lung
      adenocarcinoma cell lines in vitro.
AB  - Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase
      inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment
      of tumors. However, survival time was not extended for the patients with lung
      adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study,
      we attempt to assess the optimal schedule of the combined administration of
      pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines
      with wild-type (A549), EGFR T790M (H1975) and activating EGFR mutation (HCC827)
      were applied in vitro to assess the differential efficacy of various sequential
      regimens on cell viability, cell apoptosis and cell cycle distribution. The
      results suggested that the antiproliferative effect of the sequence of pemetrexed
      followed by icotinib/erlotinib was more effective than that of icotinib/erlotinib
      followed by pemetrexed. Additionally, a reduction of G1 phase and increased S
      phase in sequence of pemetrexed followed by icotinib/erlotinib was also observed,
      promoting cell apoptosis. Thus, the sequential administration of pemetrexed
      followed by icotinib/erlotinib exerted a synergistic effect on HCC827 and H1975
      cell lines compared with the reverse sequence. The sequential treatment of
      pemetrexed followed by icotinib/erlotinib has been demonstrated promising
      results. This treatment strategy warrants further confirmation in patients with
      advanced lung AdC.

PMID- 29371988
TI  - Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient
      derived EMP-induced endothelial dysfunction.
AB  - Background: Endothelial microparticles (EMPs) are small vesicles released by
      endothelial cells (ECs); they are considered biomarkers for endothelial
      dysfunction and therapeutic targets in diabetes-related vascular disease.
      Sirtuins have also been shown to play important roles in diabetes by regulating
      endothelial dysfunction. However, the effect of sirtuin-incorporated EMPs on
      their parental ECs remains unknown. Aim: The present study aims to investigate
      the diagnostic value of EMPs in diabetes and detect the protective effects of
      sirtuin 6 (Sirt6) mRNA -incorporated EMPs on endothelial dysfunction. Methods:
      EMPs were prepared from cultured HUVECs and venous blood from patients with
      diabetes (n=10) and from healthy volunteers (n=6) after sequential
      centrifugation. Adv-Sirt6 or Sirt6 siRNA was used to alter Sirt6 expression. EC
      angiogenesis, inflammatory phenotypes, nitric oxide (NO) formation and eNOS
      phosphorylation were used to evaluate endothelial dysfunction. Results: The
      levels of EMPs in diabetic patients and high glucose-cultured HUVECs are high,
      whereas Sirt6 expression in plasma and EMPs is low. EMPs generated from diabetic
      patients or high glucose-cultured HUVECs increase inflammatory chemokine release
      and blunt EC angiogenesis. Furthermore, EMPs enriched with Sirt6 mRNA induces EC
      angiogenesis, increases eNOS phosphorylation and impedes inflammatory chemokine
      release. Inhibition of Sirt6 mRNA expression in EMPs by siRNA hinders
      angiogenesis and eNOS phosphorylation but increases cellular inflammation.
      Conclusion: The Sirt6 mRNA-carrying EMPs may ameliorate endothelial dysfunction
      in diabetic patients.

PMID- 29371989
TI  - Synthesis and characterization of polyphosphazene microspheres incorporating
      demineralized bone matrix scaffolds controlled release of growth factor for
      chondrogenesis applications.
AB  - As a promising strategy for the successful regeneration of articular cartilage,
      tissue engineering has received increasing recognition of control release. Two
      kinds of functional poly (alanine ethyl ester-co-glycine ethyl ester) phosphazene
      microspheres with different ratios of side-substituent groups were synthesized by
      emulsion technique. The rate of degradation/hydrolysis of the polymers was
      carefully tuned to suit the desired application for control release. For
      controlled delivery of growth factors, the microspheres overcame most of severe
      side effects linked to demineralized bone matrix (DBM) scaffolds, which had been
      previously optimized for cartilage regeneration. The application of scaffolds in
      chondrogenic differentiation was investigated by subcutaneous implantation in
      nude mice. In the present study, we have provided a novel microsphere
      incorporating demineralized bone matrix (MS/DBM) scaffolds to release
      transforming growth factor-beta1 or insulin-like growth factors-1. Laser confocal
      fluorescence staining showed that the surface of microspheres was a suitable
      environment for cell attachment. Histological and immunohistochemical evaluations
      have shown that significantly more cartilaginous extracellular matrix was
      detected in MS/DBM group when compared with DBM alone group (P<0.05). In
      addition, the biomechanical test showed that this composite scaffold exhibited
      favorable mechanical strength as a delivery platform. In conclusion, we
      demonstrated that MS/DBM scaffolds was sufficient to support stem bone marrow
      derived mesenchymal stem cells chondrogenesis and neo-cartilage formation.

PMID- 29371990
TI  - CDC5L drives FAH expression to promote metabolic reprogramming in melanoma.
AB  - Metabolic reprogramming allows tumor cells to thrive in the typically hypoxic
      tumor microenvironment. Using immunodetection and clinical data analyses, we
      demonstrate here that fumarylacetoacetate hydrolase (FAH) is highly expressed in
      melanoma and correlates with poor survival. FAH knockdown inhibits proliferation
      and migration, while promoting apoptosis in melanoma cells, result in prolonged
      survival in tumor-bearing mice. Molecular analyses using real time RT-PCR,
      western blot, and 13C tracing showed that these changes are driven by strong
      stimulation of anaplerotic reactions through the TCA cycle and the pentose
      phosphate pathway, resulting in increased fatty acid and nucleotide synthesis.
      Using bioinformatic, ChIP-PCR, and gene silencing analyses, we determined that
      cell division cycle 5-like protein (CDC5L) is an important transcription factor
      regulating FAH expression in melanoma cells. These findings reveal that FAH
      induces metabolic reprogramming in melanoma and so emerges as both a potentially
      useful independent prognostic indicator and an attractive therapeutic target.

PMID- 29371991
TI  - Association of miR-196a2 rs11614913 and miR-499 rs3746444 polymorphisms with
      cancer risk: a meta-analysis.
AB  - Background: MicroRNAs (miRNAs) are small non-coding RNA molecules, which
      participate in diverse biological processes and may regulate tumor suppressor
      genes or oncogenes. Rs11614913 in miR-196a2 and rs3746444 in miR-499 are shown to
      associate with increased/decreased cancer risk. This meta-analysis was performed
      to systematically assess the overall association. Materials and Methods: We
      searched Pubmed, Web of Knowledge, EMBASE, Chinese National Knowledge
      Infrastructure (CNKI) databases until December 2016 to identify eligible studies.
      Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the
      strength of the associations. Results: We assessed published studies of the
      association between these microRNA polymorphisms and cancer risk from 56 studies
      with 21958/26436 cases/controls for miR-196a2 and from 37 studies with
      13759/17946 cases/controls for miR-499. The results demonstrated that miR-196a2
      rs11614913 was significantly associated with a decreased cancer risk, in
      particular with a decreased risk for colorectal cancer and gastric cancer, or for
      Asian population subgroup. In addition, miR-499 rs3746444 polymorphism was
      observed as a risk factor for cancers, in particular, for breast cancer, or for
      in the Asian population. Conclusions: Our meta-analysis suggests that the
      rs11614913 most likely contributes to decreased susceptibility to cancer,
      especially in Asians and colorectal cancer and gastric cancer, and that the
      rs3746444 may increase risk for cancer. Furthermore, more well-designed studies
      with large sample size are still necessary to further elucidate the association
      between polymorphisms and different kinds of cancers risk.

PMID- 29371992
TI  - Prediction of low-risk breast cancer using quantitative DCE-MRI and its
      pathological basis.
AB  - Purpose: This study aimed to evaluate the difference of mass in dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) characteristics between low-risk
      and non-low-risk breast cancers and to explore the possible pathological basis.
      Materials and Methods: Approval from the institutional review board and informed
      consent were acquired for this study. The MR images of 104 patients with
      pathologically proven breast cancer (104 lesions) were prospectively analyzed.
      All of included patients were Chinese woman. The DCE-MRI morphologic findings,
      apparent diffusion coefficient (ADC) values, quantitative DCE-MRI parameters, and
      pathological biomarkers between the two subtypes of breast cancer were compared.
      The quantitative DCE-MRI parameters and ADC values were added to the morphologic
      features in multivariate models to evaluate diagnostic performance in predicting
      low-risk breast cancer. The values were further subjected to the receiver
      operating characteristic (ROC) curve analysis. Results: Low-risk tumors showed
      significantly lower Ktrans and Kepvalues (t = 2.065, P = 0.043 and t = 3.548, P =
      0.001, respectively) and higher ADC value (t = 4.713, P = 0.000) than non-low
      risk breast cancers. Our results revealed no significant differences in clinic
      data and conventional imaging findings between the two breast cancer subtypes.
      Adding the quantitative DCE-MRI parameters and ADC values to conventional MRI
      improved the diagnostic performance of MRI: The area under the ROC improved from
      0.63 to 0.91. Low-risk breast cancers showed significantly lower matrix
      metalloproteinase (MMP)-2 expression (P = 0.000), lower MMP-9 expression (P =
      0.001), and lower microvessel density (MVD) values (P = 0.008) compared with non
      low-risk breast cancers. Ktrans and Kep values were positively correlated with
      pathological biomarkers. The ADC value showed a significant inverse correlation
      with pathological biomarkers. Conclusions: The prediction parameter using Ktrans,
      Kep, and ADC obtained on DCE-MRI and diffusion-weighted imaging could facilitate
      the identification of low-risk breast cancers. Decreased biological factors,
      including MVD, vascular endothelial growth factor, MMP-2, and MMP-9, may explain
      the possible pathological basis.

PMID- 29371993
TI  - Genomic alterations of ERBB receptors in cancer: clinical implications.
AB  - The ERBB family of receptor tyrosine kinases has been implicated in
      carcinogenesis for over three decades with rigorous attention to EGFR and HER2.
      ERBB receptors, consisting of EGFR, HER2, HER3, and HER4 are part of a
      complicated signaling network that activates downstream signaling pathways
      including PI3K/AKT, Ras/Raf/MAPK, JAK/STAT and PKC. It is well established that
      EGFR is amplified and/or mutated in gliomas and non-small-cell lung carcinoma
      while HER2 is amplified and/or over-expressed in breast, gastric, ovarian, non
      small cell lung carcinoma, and several other tumor types. With the advent of next
      generation sequencing and large scale efforts to explore the entire spectrum of
      genomic alterations involved in human cancer progression, it is now appreciated
      that somatic ERBB receptor mutations occur at relatively low frequencies across
      multiple tumor types. Some of these mutations may represent oncogenic driver
      events; clinical studies are underway to determine whether tumors harboring these
      alterations respond to small molecule EGFR/HER2 inhibitors. Recent evidence
      suggests that some somatic ERBB receptor mutations render resistance to FDA
      approved EGFR and HER2 inhibitors. In this review, we focus on the landscape of
      genomic alterations of EGFR, HER2, HER3 and HER4 in cancer and the clinical
      implications for patients harboring these alterations.

PMID- 29371995
TI  - Fluorescence Detection of Cell Death in Liver of Mice Treated with Thioacetamide.
AB  - The purpose of this study was to detect cell death in the liver of mice treated
      with thioacetamide (TAA) using fluorescence bioimaging and compare this outcome
      with that using conventional histopathological examination. At 6 weeks of age, 24
      mice were randomly divided into three groups: group 1 (G1), control group; group
      2 (G2), fluorescence probe control group; group 3 (G3), TAA-treated group. G3
      mice were treated with TAA. Twenty-two hours after TAA treatment, G2 and G3 mice
      were treated with Annexin-Vivo 750. Fluorescence in vivo bioimaging was performed
      by fluorescence molecular tomography at two hours after Annexin-Vivo 750
      treatment, and fluorescence ex vivo bioimaging of the liver was performed. Liver
      damage was validated by histopathological examination. In vivo bioimaging showed
      that the fluorescence intensity was increased in the right upper part of G3 mice
      compared with that in G2 mice, whereas G1 mice showed no signal. Additionally ex
      vivo bioimaging showed that the fluorescence intensity was significantly
      increased in the livers of G3 mice compared with those in G1 or G2 mice (p <
      0.05). Histopathological examination of the liver showed no cell death in G1 and
      G2 mice. However, in G3 mice, there was destruction of hepatocytes and increased
      cell death. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining
      confirmed many cell death features in the liver of G3 mice, whereas no
      pathological findings were observed in the liver of G1 and G2 mice. Taken
      together, fluorescence bioimaging in this study showed the detection of cell
      death and made it possible to quantify the level of cell death in male mice. The
      outcome was correlated with conventional biomedical examination. As it was
      difficult to differentiate histological location by fluorescent bioimaging, it is
      necessary to develop specific fluorescent dyes for monitoring hepatic disease
      progression and to exploit new bioimaging techniques without dye-labeling.

PMID- 29371996
TI  - Molecular Mechanism of Atopic Dermatitis Induction Following Sensitization and
      Challenge with 2,4-Dinitrochlorobenzene in Mouse Skin Tissue.
AB  - Laboratory animal models have been developed to investigate preventive or
      therapeutic effect of medicinal products, or occurrence or progression mechanism
      of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease.
      The murine model with immunologic phenomena resembling human AD was introduced,
      which demonstrated skewedness toward predominance of type-2 helper T cell
      reactivity and pathophysiological changes similar as human AD following 2,4
      dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on
      the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice
      treated with DNCB, and each tissue was equally divided into two sections; one for
      protein and the other for mRNA analysis. Expression of filaggrin, an important
      protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA
      expression for cytokines was determined through semi-quantitative reverse
      transcriptase polymerase chain reaction. Expression of filaggrin protein was
      significantly enhanced in the mice treated with DNCB compared with the vehicle
      (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without
      any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA
      expression, cytokines involved in activity of type-1 helper T (TH1) cell, was
      significantly downregulated in the AD group compared with other control groups.
      These results suggest that suppression of TH1 cell-mediated immune response could
      be reflected into the skin tissue of mice treated with DNCB for AD induction, and
      disturbance of keratinocyte integrity might evoke a compensatory mechanism.

PMID- 29371997
TI  - Inhibition of Adipocyte Differentiation by Anthocyanins Isolated from the Fruit
      of Vitis coignetiae Pulliat is Associated with the Activation of AMPK Signaling
      Pathway.
AB  - Anthocyanins are naturally occurring water-soluble polyphenolic pigments in
      plants that have been shown to protect against cardiovascular diseases, and
      certain cancers, as well as other chronic human disorders. However, the anti
      obesity effects of anthocyanins are not fully understood. In this study, we
      investigated the effects of anthocyanins isolated from the fruit of Vitis
      coignetiae Pulliat on the adipogenesis of 3T3-L1 preadipocytes. Our data
      indicated that anthocyanins attenuated the terminal differentiation of 3T3-L1
      preadipocytes, as confirmed by a decrease in the number of lipid droplets, lipid
      content, and triglyceride production. During this process, anthocyanins
      effectively enhanced the activation of the AMP-activated protein kinase (AMPK);
      however, this phenomenon was inhibited by the co-treatment of compound C, an
      inhibitor of AMPK. Anthocyanins also inhibited the expression of adipogenic
      transcription factors, including peroxisome proliferator-activated receptor
      gamma, CCAAT/enhancer-binding protein a and b, and sterol regulatory element
      binding protein-1c. In addition, anthocyanins were found to potently inhibit the
      expression of adipocyte-specific genes, including adipocyte fatty acid-binding
      protein, leptin, and fatty acid synthase. These results indicate that
      anthocyanins have potent anti-obesity effects due to the inhibition of adipocyte
      differentiation and adipogenesis, and thus may have applications as a potential
      source for an anti-obesity functional food agent.

PMID- 29371998
TI  - Protective Effect of Isoliquiritigenin against Ethanol-Induced Hepatic Steatosis
      by Regulating the SIRT1-AMPK Pathway.
AB  - Ethanol-induced fat accumulation, the earliest and most common response of the
      liver to ethanol exposure, may be involved in the pathogenesis of liver diseases.
      Isoliquiritigenin (ISL), an important constituent of Glycyrrhizae Radix, is a
      chalcone derivative that exhibits antioxidant, anti-inflammatory, and
      phytoestrogenic activities. However, the effect of ISL treatment on lipid
      accumulation in hepatocytes and alcoholic hepatitis remains unclear. Therefore,
      we evaluated the effect and underlying mechanism of ISL on ethanol-induced
      hepatic steatosis by treating AML-12 cells with 200 mM ethanol and/or ISL (0~50
      MUM) for 72 hr. Lipid accumulation was assayed by oil red O staining, and the
      expression of sirtuin1 (SIRT1), sterol regulatory element-binding protein-1c
      (SREBP-1c), AMP-activated protein kinase (AMPK), and peroxisome proliferator
      activated receptor alpha (PPARalpha) was studied by western blotting. Our results
      indicated that ISL treatment upregulated SIRT1 expression and downregulated SREBP
      1c expression in ethanol-treated cells. Similarly, oil red O staining revealed a
      decrease in ethanol-induced fat accumulation upon co-treatment of ethanol-treated
      cells with 10, 20, and 50 MUM of ISL. These findings suggest that ISL can reduce
      ethanol induced-hepatic lipogenesis by activating the SIRT1-AMPK pathway and thus
      improve lipid metabolism in alcoholic fatty livers.

PMID- 29371999
TI  - Antioxidant and Skin Anti-Aging Effects of Marigold Methanol Extract.
AB  - The objective of this study was to evaluate the antioxidant and anti-aging
      effects of marigold methanol extract (MGME) in human dermal fibroblasts. Total
      polyphenolic and flavonoid contents in MGME were 74.8 mg TAE (tannic acid
      equivalent)/g and 85.6 mg RE (rutin equivalent)/g, respectively. MGME (500
      MUg/mL) increased 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-3
      ethylbenzothiazoline-6-sulfonic acid (ABTS) radical-scavenging, and superoxide
      dismutase (SOD)-like antioxidant activities by 36.5, 54.7, and 14.8%,
      respectively, compared with the control. At 1,000 MUg/mL, these activities
      increased by 63.7, 70.6, and 20.6%, respectively. MGME (100 MUg/mL) significantly
      increased the synthesis of type 1 procollagen by 83.7% compared with control
      treatment. It also significantly decreased Matrix Metalloproteinase-2 (MMP-2)
      activity and MMP-1 mRNA expression by 36.5% and 69.5%, respectively; however, it
      significantly increased laminin-5 mRNA expression by 181.2%. These findings
      suggest that MGME could protect human skin against photo-aging by attenuating
      oxidative damage, suppressing MMP expression and/or activity as well as by
      stimulating collagen synthesis.

PMID- 29372001
TI  - Subacute Inhalation Toxicity of Cyclohexanone in B6C3F1 Mice.
AB  - Cyclohexanone (C6H10O, CAS No. 108-94-1) is a colorless oily liquid obtained
      through the oxidation of cyclohexane or dehydrogenation of phenol. It is used in
      the manufacture of adhesives, sealant chemicals, agricultural chemicals, paint
      and coating additives, solvent, electrical and electronic products, paints and
      coatings, photographic supplies, film, photochemicals, and as an intermediate in
      nylon production. Owing to the lack of information on repeated inhalation
      toxicity of cyclohexaone, in this study, we aimed to characterize the subacute
      inhalation toxicity. B6C3F1 mice were exposed to 0, 50, 150, and 250 ppm of
      cyclohexanone for 6 hr/day, 5 days/week for 4 weeks via whole-body inhalation in
      accordance with the OECD Test Guideline 412 (subacute inhalation toxicity: 28-day
      study). Mortality, clinical signs, body weights, food consumption, hematology,
      serum biochemistry, organ weights, as well as gross and histopathological
      findings were evaluated between the control and exposure groups. No mortality or
      remarkable clinical signs were observed during the study. No adverse effects on
      body weight, food consumption, hematology, serum biochemistry, and organ weights,
      gross or histopathological lesions were observed in any male or female mice in
      any of the exposure groups, although some statistically significant changes were
      observed in organ weights. We concluded that no observable adverse effect level
      (NOAEL) is above 250 ppm in mice exposed to cyclohexanone for 6 hr/day for 5
      days/week.

PMID- 29371994
TI  - Microglia at center stage: a comprehensive review about the versatile and unique
      residential macrophages of the central nervous system.
AB  - Microglia cells are the unique residential macrophages of the central nervous
      system (CNS). They have a special origin, as they derive from the embryonic yolk
      sac and enter the developing CNS at a very early stage. They play an important
      role during CNS development and adult homeostasis. They have a major contribution
      to adult neurogenesis and neuroinflammation. Thus, they participate in the
      pathogenesis of neurodegenerative diseases and contribute to aging. They play an
      important role in sustaining and breaking the blood-brain barrier. As innate
      immune cells, they contribute substantially to the immune response against
      infectious agents affecting the CNS. They play also a major role in the growth of
      tumours of the CNS. Microglia are consequently the key cell population linking
      the nervous and the immune system. This review covers all different aspects of
      microglia biology and pathology in a comprehensive way.

PMID- 29372000
TI  - Highly Active Antiretroviral Therapy Alters Sperm Parameters and Testicular
      Antioxidant Status in Diet-Induced Obese Rats.
AB  - The efficacy of highly active antiretroviral therapy (HAART) has led to an
      increase demand for therapeutic use, thereby necessitating investigation into
      drug toxicity. This study was designed to investigate the in vivo effects of
      HAART on sperm parameters and testicular oxidative stress in lean and obese rats.
      Wistar rats (males, n = 40, weighing 180~200 g) were assigned randomly into 4
      groups and treated accordingly for 16 weeks as follows: Control (C): lean group
      fed with standard rat chow; Diet induced obesity (DIO): obese animals fed a high
      caloric diet; C + ART: lean animals treated with HAART; DIO + ART: obese animals
      treated with HAART. An antiretroviral drug combination of Tenofovir,
      Emtricitabine and Efavirenz at a dose of 17, 26 and 50 mg/kg/day was administered
      for the latter 6 weeks via jelly cube feeding. At the end of the experimental
      period, sperm analysis was performed on sperm collected from the caudal
      epididymis, while the testis was homogenized for antioxidant enzyme and lipid
      peroxidation assays. Results showed that HAART significantly decreased sperm
      motility (p < 0.05) in both lean and obese animals, and viability (p < 0.05) in
      the DIO group. Testicular glutathione, catalase and superoxide dismutase were
      significantly decreased (p < 0.05), while Thiobarbituric acid reactive substances
      (TBARS) levels were significantly increased (p < 0.05) when the DIO+ART group was
      compared to Control group. Thus, the decreased sperm qualities associated with
      HAART might be as a result of increased testicular oxidative stress prominent in
      obese animals.

PMID- 29372002
TI  - Subchronic Oral Dose Toxicity Study of Enterococcus Faecalis 2001 (EF 2001) in
      Mice.
AB  - As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001)
      prepared using heat-treatment bacillus mort body EF 2001 in mice, this study
      examined the toxicity of EF 2001 in single and repeated administrations following
      the previous report in order to apply this product to preventive medicine. The
      safety of oral ingestion of EF 2001 was examined in 6-week-old male and female
      ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day
      administrated by gavage of the maximum acceptable dose of EF 2001. The study was
      conducted using distilled water as a control following the methods for general
      toxicity studies described in the "Guidelines for Non-clinical Studies of
      Pharmaceutical Products 2002". As a control, 1) observation of general
      conditions, 2) measurement of body weight, 3) determination of food consumption,
      4) determination of water consumption, 5) blood test and urinalysis and 6)
      pathological examination were performed for the administration of EF 2001. Mice
      received EF 2001 for 13 weeks and results were compared with those of the control
      group that received distilled water. The results of the above examinations
      revealed no significant differences between control and EF 2001 groups for both
      males and females. Thus, no notable toxicity was confirmed with single and
      repeated oral administrations of EF 2001. Oral administration in the above doses
      did not result in abnormal symptoms or death during the observation period. No
      abnormalities in blood cell count or organ weights were seen. Without any
      evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely
      affect living organisms. The 50% lethal dose of EF 2001 with oral administration
      in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male
      and female mice. Therefore, LD50 value for animals was 5,000 mg/kg or more.

PMID- 29372003
TI  - Pretreatment of Low-Dose and Super-Low-Dose LPS on the Production of In Vitro LPS
      Induced Inflammatory Mediators.
AB  - Pretreatment of low-dose lipopolysaccharide (LPS) induces a hyporesponsive state
      to subsequent secondary challenge with high-dose LPS in innate immune cells,
      whereas super-low-dose LPS results in augmented expression of pro-inflammatory
      cytokines. However, little is known about the difference between super-low-dose
      and low-dose LPS pretreatments on immune cell-mediated inflammatory and hepatic
      acute-phase responses to secondary LPS. In the present study, RAW 264.7 cells,
      EL4 cells, and Hepa-1c1c7 cells were pretreated with super-low-dose LPS (SL-LPS:
      50 pg/mL) or low-dose LPS (L-LPS: 50 ng/mL) in fresh complete medium once a day
      for 2~3 days and then cultured in fresh complete medium for 24 hr or 48 hr in the
      presence or absence of LPS (1~10 MUg/mL) or concanavalin A (Con A). SL-LPS
      pretreatment strongly enhanced the LPS-induced production of tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-6, TNF-alpha/IL-10, prostaglandin E2 (PGE2),
      and nitric oxide (NO) by RAW 264.7 cells compared to the control, whereas L-LPS
      increased IL-6 and NO production only. SL-LPS strongly augmented the Con A
      induced ratios of interferon (IFN)-gamma/IL-10 in EL4 cells but decreased the LPS
      induced ratios of IFN-gamma/IL-10 compared to the control, while L-LPS decreased
      the Con A- and LPS-induced ratios of IFN-gamma/IL-10. SL-LPS enhanced the LPS
      induced production of IL-6 by Hepa1c1c-7 cells compared to the control, while L
      LPS increased IL-6 but decreased IL-1beta and C reactive protein (CRP) levels. SL
      LPS pretreatment strongly enhanced the LPS-induced production of TNF-alpha, IL-6,
      IL-10, PGE2, and NO in RAW 264.7 cells, and the IL-6, IL-1beta, and CRP levels in
      Hepa1c1c-7 cells, as well as the ratios of IFN-gamma/IL-10 in LPS- and Con A
      stimulated EL4 cells compared to L-LPS. These findings suggest that pre
      conditioning of SL-LPS may contribute to the mortality to secondary infection in
      sepsis rather than pre-conditioning of L-LPS.

PMID- 29372004
TI  - Mental Stress from Animal Experiments: a Survey with Korean Researchers.
AB  - Animal experiments have been widely conducted in the life sciences for more than
      a century, and have long been a subject of ethical and societal controversy due
      to the deliberate infliction of harm upon sentient animals. However, the harmful
      use of animals may also negatively impact the mental health of researchers
      themselves. We sought to evaluate the anxiety level of researchers engaged in
      animal use to analyse the mental stress from animal testing. The State Anxiety
      Scale of the State-Trait Anxiety Inventory (STAI) was used to evaluate how
      researchers feel when they conduct animal, as opposed to non-animal, based
      experiments (95 non-animal and 98 animal testing researchers). The Trait Anxiety
      Scale of STAI was employed to measure proneness to anxiety, namely the base trait
      of the researchers. Additionally, the information on sex, age, education, income,
      and total working periods was collected. While the Trait Anxiety scores were
      comparable (41.5 +/- 10.9 versus 42.9 +/- 10.1, p = 0.3682, t-test), the State
      Anxiety scores were statistically significantly higher for animal users than non
      animal users (45.1 +/- 10.7 versus 41.3 +/- 9.4, p = 0.011). This trend was
      consistent for both male and female. Notably, younger animal testers (<= 30 years
      of age) with less work experience (<= 2 years) and lower income level (<= 27,000
      USD) exhibited higher anxiety scores, whereas these factors did not affect the
      anxiety level of non-animal users. The present study demonstrated that
      participation in animal experiments can negatively impact the mental health of
      researchers.

PMID- 29372005
TI  - Peptide self-assembly into lamellar phases and the formation of lipid-peptide
      nanostructures.
AB  - Lipids exhibit an extraordinary polymorphism in self-assembled mesophases, with
      lamellar phases as biologically most relevant representative. To mimic lipid
      lamellar phases with amphiphilic designer peptides, seven systematically varied
      short peptides were engineered. Indeed, four peptide candidates (V4D, V4WD,
      V4WD2, I4WD2) readily self-assembled into lamellae in aqueous solution: small
      angle X-ray scattering patterns (SAXS) revealed ordered lamellar structures with
      a repeat distance of ~4-5 nm. Transmission electron microscopy (TEM) images
      confirmed the presence of stacked sheets. Two derivatives (V3D and V4D2) remained
      as loose aggregates dispersed in solution; one peptide (L4WD2) formed twisted
      tapes with internal lamellae and an antiparallel beta-type monomer alignment. To
      understand the interaction of peptides with lipids they were mixed with
      phosphatidylcholines. Low peptide concentrations (1.1 mM) induced the formation
      of a heterogeneous mixture of vesicular structures: large multilamellar vesicles
      (d-spacing ~6.3 nm) coexisted with oligo- or unilamellar vesicles (~50 nm in
      diameter) and bicelle-like structures (~45 nm length, ~18 nm width). High peptide
      concentrations (11 mM) led to unilamellar vesicles (ULV, diameter ~260-280 nm)
      with a homogeneous mixing of lipids and peptides. SAXS revealed the temperature
      dependent fine structure of these ULVs: at 25  degrees C the bilayer is in a
      fully interdigitated state (headgroup-to-headgroup distance dhh ~2.9 nm), whereas
      at 50  degrees C this interdigitation opens up (dhh ~3.6 nm). Our results
      highlight the versatility of self-assembled peptide superstructures: subtle
      changes in the amino acid composition are key design elements in creating peptide
      or lipid-peptide nanostructures with the same richness in morphology as known
      from the lipid-world.

PMID- 29372006
TI  - Dissecting the molecular mechanisms of gene x environment interactions:
      implications for diagnosis and treatment of stress-related psychiatric disorders.
AB  - Epidemiological studies indicate a combined contribution of genetic and
      environmental factors, mainly exposure to adverse life events, in the risk for
      psychiatric disease. Understanding how adverse life events interact with genetic
      predisposition on the molecular level to shape risk and resilience to psychiatric
      disorders may yield important insight into disease mechanism. Using the example
      of the molecular mechanisms of interaction of functional genetic variants within
      the stress-regulating gene FKBP5 and early adversity, it is delineated how this
      interaction could contribute to transdiagnostic disease risk via a combined
      genetic and epigenetic disinhibition of FKBP5 transcription. This knowledge may
      now allow to develop biomarkers for a transdiagnostic subset of psychiatric
      patients and to personalize treatment.

PMID- 29372007
TI  - Clinical Virtual Reality tools to advance the prevention, assessment, and
      treatment of PTSD.
AB  - Numerous reports indicate that the incidence of posttraumatic stress disorder
      (PTSD) in Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn
      (OEF/OIF/OND) military personnel has created a significant behavioural healthcare
      challenge. These findings have served to motivate research on how to better
      develop and disseminate evidence-based treatments for PTSD. The current article
      presents the use of Virtual Reality (VR) as a clinical tool to address the
      assessment, prevention, and treatment of PTSD, based on the VR projects that were
      evolved at the University of Southern California Institute for Creative
      Technologies since 2004. A brief discussion of the definition and rationale for
      the clinical use of VR is followed by a description of a VR application designed
      for the delivery of prolonged exposure (PE) for treating Service Members (SMs)
      and Veterans with combat- and sexual assault-related PTSD. The expansion of the
      virtual treatment simulations of Iraq and Afghanistan for PTSD assessment and
      prevention is then presented. This is followed by a forward-looking discussion
      that details early efforts to develop virtual human agent systems that serve the
      role of virtual patients for training the next generation of clinical providers,
      as healthcare guides that can be used to support anonymous access to trauma
      relevant behavioural healthcare information, and as clinical interviewers capable
      of automated behaviour analysis of users to infer psychological state. The paper
      will conclude with a discussion of VR as a tool for breaking down barriers to
      care in addition to its direct application in assessment and intervention.

PMID- 29372008
TI  - Early indicators of problematic grief trajectories following bereavement.
AB  - Background: Little is known about the development of Prolonged Grief Disorder
      (PGD) symptoms over time in adults. For clinical purposes, it would be useful to
      have knowledge about early indicators of a problematic grief trajectory.
      Objective: This study aimed to identify classes of bereaved individuals with
      similar trajectories of PGD symptoms and to design a provisional screening tool
      including symptoms predicting membership of classes with problematic grief
      trajectories. Method: In a Dutch sample of 166 bereaved individuals, we conducted
      a latent class analysis to identify classes of bereaved individuals with similar
      trajectories of PGD symptoms between two time points (mean of 6 and 18 months
      post-loss, respectively). Next, we used Receiver Operating Characteristic (ROC)
      analyses to examine which symptoms at baseline best predicted membership of
      classes with problematic grief trajectories. Results: We found four different
      classes: a class including individuals with persistent high PGD symptoms (class
      1, 6%), a class of individuals with persistent moderate PGD symptoms (class 2,
      35%), a class of individuals with slightly decreasing moderate PGD symptoms
      (class 3, 33%) and a class of individuals with persistent low PGD symptoms (class
      4, 26%). The endorsement of symptoms 'yearning', 'stunned', 'life is empty' and
      'bitterness' as present 'often' during the preceding month at baseline best
      predicted membership of class 1 or 2. Conclusions: Two classes of individuals
      with problematic grief trajectories were identified. Four symptoms were found
      which could act as early indicators of these two classes in a provisional
      screening tool.

PMID- 29372009
TI  - Attachment styles, grief responses, and the moderating role of coping strategies
      in parents bereaved by the Sewol ferry accident.
AB  - Background: Previous studies on the influence of different types of attachment on
      grief responses have yielded contradictory outcomes. Little research has been
      conducted to identify the psychological processes that moderate the relationship
      between attachment representations and patterns of grief in disaster-related
      grief. Objective: The present study examines the effects of different attachment
      types on the grief responses of parents bereaved by loss of a child in a ferry
      accident, along with the moderating role of coping strategies. Methods: Bereaved
      parents (n = 81) completed self-report questionnaires evaluating attachment,
      coping strategies, complicated grief, and shame/guilt. We performed correlational
      analyses to examine the associations among variables. We also conducted
      hierarchical regression analyses and simple slope analyses to examine the
      moderation effects of coping strategies. Results: Anxious attachment was
      associated with severe shame/guilt, and avoidant attachment correlated with
      complicated grief. Anxious attachment was positively associated with all types of
      coping strategies, and avoidant attachment was negatively related to problem- and
      emotion-focused coping. The use of problem-focused coping strategies was a
      significant moderator of the relationship between the avoidant attachment
      dimension and shame/guilt. Avoidant attachment had a significant effect on
      shame/guilt in groups with a high level of problem-focused coping. In contrast,
      none of the coping strategies significantly moderated the relationship between
      anxious attachment and grief response. Conclusions: The results suggest that
      people with highly avoidant attachment might be overwhelmed by shame and guilt
      when they try to use problem-focused coping strategies. This finding suggests
      that grief interventions should be organized with consideration of individual
      differences in attachment representations.

PMID- 29372010
TI  - PTSD and Complex PTSD: ICD-11 updates on concept and measurement in the UK, USA,
      Germany and Lithuania.
AB  - The 11th revision to the World Health Organization's International Classification
      of Diseases (ICD-11) proposes two distinct sibling conditions: Posttraumatic
      Stress Disorder (PTSD) and Complex PTSD (CPTSD). In this paper, we aim to provide
      an update on the latest research regarding the conceptual structure and
      measurement of PTSD and CPTSD using the International Trauma Questionnaire (ITQ)
      as per ICD-11 proposals in the USA, UK, Germany and Lithuania. Preliminary
      findings suggest that CPTSD is common in clinical and population samples,
      although there may be variations across countries in prevalence rates. In
      clinical samples, preliminary evidence suggests that CPTSD is a more commonly
      observed condition than PTSD. Preliminary evidence also suggests that the ITQ
      scores are reliable and valid and can adequately distinguish between PTSD and
      CPTSD. Further cross-cultural work is proposed to explore differences in PTSD and
      CPTSD across different countries with regard to prevalence, incidence, and
      predictors of PTSD and CPTSD.

PMID- 29372011
TI  - A scoping review of ICD-11 adjustment disorder research.
AB  - Background: Adjustment disorder (AjD) is one of the most used mental disorder
      diagnoses among mental health professionals. Important revisions of the AjD
      definition in the 11th edition of the International Classification of Diseases
      (ICD-11) are proposed. AjD is included in a chapter of disorders specifically
      associated with stress in ICD-11. Objective: This paper aims to review recent
      developments in ICD-11 AjD research, and to discuss the available ICD-11 AjD
      diagnosis validation studies, AjD measures, treatment studies, and outline the
      future perspectives for AjD research and clinical practice. Methods: In total, 10
      empirical studies of AjD ICD-11 were identified and included in this review. We
      searched for studies in Embase, PubMed, PsycINFO, Scopus, PILOTS, SocINDEX, and
      via additional search by contacting authors of published empirical studies and
      reference screening. Results: Review of the studies revealed a lack of validation
      studies of the ICD-11 AjD symptom structure. AjD validation study findings are
      ambiguous, and there is still little support for the proposed two symptom
      structure of AjD for the ICD-11. A self-report AjD measure 'Adjustment Disorder
      New Module' (ADNM) based on the ICD-11 definition has been developed and used in
      all 10 reviewed studies. Two self-help interventions have been developed for the
      ICD-11 AjD, and findings from these studies indicate that self-help low-intensity
      cognitive-behavioural interventions, delivered via bibliography or internet
      based, might be effective treatment of AjD. Conclusions: The AjD definition in
      ICD-11 with a description of a new symptom profile facilitates AjD measurement
      and AjD-focused treatment developments. More studies and insights from clinical
      practice are needed to move the field of AjD research and practice forward.

PMID- 29372012
TI  - The treatment of PTSD in an older adult Norwegian woman using narrative exposure
      therapy: a case report.
AB  - The bulk of the literature on effective treatments for posttraumatic stress
      disorder (PTSD) has focused on children, adolescents, and young adults. The
      evidence on treatments for older adults is sparse. This case report presents the
      application of narrative exposure therapy (NET) for a 70-year-old Norwegian woman
      suffering from PTSD as a result of multiple childhood and late life traumatic
      events. NET is a manualized, short-term, cognitive-behavioural therapy for PTSD,
      originally developed to meet the needs of survivors of war and organized
      violence. Some aspects of NET may be a good fit for older adults, including its
      brevity, simplicity, and concrete nature. The course of therapy included
      psychoeducation, a lifeline exercise, imaginal exposure, and the creation of a
      coherent narrative. Symptoms of depression and posttraumatic stress showed
      improvement over the course of therapy and at follow-up. This suggests that NET
      may have potential as a trauma treatment for older adults.

PMID- 29372013
TI  - The mediating role of shame in the relationship between childhood bullying
      victimization and adult psychosocial adjustment.
AB  - Background: Psychological distress following experiencing bullying victimization
      in childhood has been well documented. Less is known about the impact of bullying
      victimization on psychosocial adjustment problems in young adulthood and about
      potential pathways, such as shame. Moreover, bullying victimization is often
      studied in isolation from other forms of victimization. Objective: This study
      investigated (1) whether childhood experiences of bullying victimization and
      violence were associated with psychosocial adjustment (distress, impaired
      functioning, social support barriers) in young adulthood; (2) the unique effect
      of bullying victimization on psychosocial adjustment; and (3) whether shame
      mediated the relationship between bullying victimization and these outcomes in
      young adulthood. Method: The sample included 681 respondents (aged 19-37 years)
      from a follow-up study (2017) conducted via phone interviews derived from a
      community telephone survey collected in 2013. Results: The regression analyses
      showed that both bullying victimization and severe violence were significantly
      and independently associated with psychological distress, impaired functioning,
      and increased barriers to social support in young adulthood. Moreover, causal
      mediation analyses indicated that when childhood physical violence, sexual abuse,
      and sociodemographic factors were controlled, shame mediated 70% of the
      association between bullying victimization and psychological distress, 55% of the
      association between bullying victimization and impaired functioning, and 40% of
      the association between bullying victimization and social support barriers.
      Conclusions: Our findings support the growing literature acknowledging bullying
      victimization as a trauma with severe and long-lasting consequences and indicate
      that shame may be an important pathway to continue to explore. The unique effect
      of bullying victimization, over and above the effect of violence, supports the
      call to integrate the two research fields.

PMID- 29372014
TI  - A psychometric assessment of Disturbances in Self-Organization symptom indicators
      for ICD-11 Complex PTSD using the International Trauma Questionnaire.
AB  - Background: Two 'sibling disorders' have been proposed for the 11th version of
      the International Classification of Diseases (ICD-11): Posttraumatic Stress
      Disorder (PTSD) and Complex PTSD (CPTSD). To date, no research has attempted to
      identify the optimal symptom indicators for the 'Disturbances in Self
      Organization' (DSO) symptom cluster. Objective: The aim of the current study was
      to assess the psychometric performance of scores of 16 potential DSO symptom
      indicators from the International Trauma Questionnaire (ITQ). Criteria relating
      to score variability and their ability to discriminate were employed. Method:
      Participants (N = 1839) were a nationally representative household sample of non
      institutionalized adults currently residing in the US. Item scores from the ITQ
      were examined in relation to basic criteria associated with interpretability,
      variability, homogeneity, and association with functional impairment. The
      performance of the DSO symptoms was also assessed using 1- and 2-parameter item
      response theory (IRT) models. Results: The distribution of responses for all DSO
      indicators met the criteria associated with interpretability, variability,
      homogeneity, and association with functional impairment. The 1-parameter graded
      response model was considered the best model and indicated that each set of
      indictors performed very similarly. Conclusions: The ITQ contains 16 DSO symptom
      indicators and they perform well in measuring their respective symptom cluster.
      There was no evidence that particular indicators were 'better' than others, and
      it was concluded that the indicators are essentially interchangeable.

PMID- 29372015
TI  - Training the next generation of psychotraumatologists: COllaborative Network for
      Training and EXcellence in psychoTraumatology (CONTEXT).
AB  - In this paper we present a description of the Horizon2020, Marie Sklodowska-Curie
      Action funded, research and training programme CONTEXT: COllaborative Network for
      Training and EXcellence in psychoTraumatology. The three objectives of the
      programme are put forward, each of which refers to a key component of the CONTEXT
      programme. First, we summarize the 12 individual research projects that will take
      place across three priority populations: (i) refugees and asylum seekers, (ii)
      first responders, and (iii) perpetrators and survivors of childhood and gender
      based violence. Second, we detail the mentoring and training programme central to
      CONTEXT. Finally, we describe how the research, together with the training, will
      contribute towards better policy, guidelines, and practice within the field of
      psychotraumatology.

PMID- 29372016
TI  - Dialectical behaviour therapy for posttraumatic stress disorder related to
      childhood sexual abuse: a pilot study in an outpatient treatment setting.
AB  - Background: Dialectical behaviour therapy for posttraumatic stress disorder (DBT
      PTSD), which is tailored to treat adults with PTSD and co-occurring emotion
      regulation difficulties, has already demonstrated its efficacy, acceptance and
      safety in an inpatient treatment setting. It combines elements of DBT with trauma
      focused cognitive behavioural interventions. Objective: To investigate the
      feasibility, acceptance and safety of DBT-PTSD in an outpatient treatment setting
      by therapists who were novice to the treatment, we treated 21 female patients
      suffering from PTSD following childhood sexual abuse (CSA) plus difficulties in
      emotion regulation in an uncontrolled clinical trial. Method: The Clinician
      Administered PTSD Symptom Scale (CAPS), the Davidson Trauma Scale (DTS), the
      Borderline Section of the International Personality Disorder Examination (IPDE)
      and the Borderline Symptom List (BSL-23) were used as primary outcomes. For
      secondary outcomes, depression and dissociation were assessed. Assessments were
      administered at pretreatment, post-treatment and six-week follow-up. Results:
      Improvement was significant for PTSD as well as for borderline personality
      symptomatology, with large pretreatment to follow-up effect sizes for completers
      based on the CAPS (Cohens d = 1.30), DTS (d = 1.50), IPDE (d = 1.60) and BSL-23
      (d = 1.20). Conclusion: The outcome suggests that outpatient DBT-PTSD can safely
      be used to reduce PTSD symptoms and comorbid psychopathology in adults who have
      experienced CSA.

PMID- 29372018
TI  - Sales promotion by wholesalers affects general practitioners' prescription
      behaviours in Japan.
AB  - Background: One method for promoting drugs in Japan has been utilizing
      wholesalers for promotion; however, the effectiveness of the sales promotion has
      been brought into question. Methods: A total of 74,552 responses were collected
      from an internet survey of 511 prescribing doctors in hospitals with less than 19
      beds, which recalled the visits by wholesalers' sales representatives (MS) in
      2014. Each assessed the degree to which MS and/or sales representatives from a
      pharmaceutical company (MR) influenced a decision to prescribe each drug. The
      responses were analysed using the chi-square test and Goodman-Kruskal's gamma to
      evaluate the association between MS calls and doctors' prescription orders.
      Results: Results showed a significant effect of the MS calls on doctors'
      behaviours in terms of new drug prescriptions and subsequent behaviours. The
      results by therapeutic category showed a similar strong influence of the joint
      calls on new prescriptions on some therapeutic classes. The MS calls
      significantly influenced doctors to maintain and increase the prescription volume
      (p < 0.01). Conclusion: This paper demonstrates that sales promotion on the part
      of MSs and MRs adds value to the prescription decisions. Moreover, results
      suggest that MSs enhance prescription outcomes in competitive therapeutic
      categories.

PMID- 29372019
TI  - Can predictive biomarkers of chronic pain find in the immune system?

PMID- 29372017
TI  - Therapeutic biomaterials based on extracellular vesicles: classification of bio
      engineering and mimetic preparation routes.
AB  - Extracellular vesicles (EVs) are emerging as novel theranostic tools. Limitations
      related to clinical uses are leading to a new research area on design and
      manufacture of artificial EVs. Several strategies have been reported in order to
      produce artificial EVs, but there has not yet been a clear criterion by which to
      differentiate these novel biomaterials. In this paper, we suggest for the first
      time a systematic classification of the terms used to build up the artificial EV
      landscape, based on the preparation method. This could be useful to guide the
      derivation to clinical trial routes and to clarify the literature. According to
      our classification, we have reviewed the main strategies reported to date for
      their preparation, including key points such as: cargo loading, surface targeting
      strategies, purification steps, generation of membrane fragments for the
      construction of biomimetic materials, preparation of synthetic membranes inspired
      in EV composition and subsequent surface decoration.

PMID- 29372020
TI  - Pain medication and long QT syndrome.
AB  - Long QT syndrome is a cardiac repolarization disorder and is associated with an
      increased risk of torsades de pointes. The acquired form is most often
      attributable to administration of specific medications and/or electrolyte
      imbalance. This review provides insights into the risk for QT prolongation
      associated with drugs frequently used in the treatment of chronic pain. In the
      field of pain medicine all the major drug classes (i.e. NSAIDs, opioids,
      anticonvulsive and antidepressant drugs, cannabinoids, muscle relaxants) contain
      agents that increase the risk of QT prolongation. Other substances, not used in
      the treatment of pain, such as proton pump inhibitors, antiemetics, and diuretics
      are also associated with long QT syndrome. When the possible benefits of therapy
      outweigh the associated risks, slow dose titration and electrocardiography
      monitoring are recommended.

PMID- 29372021
TI  - Allopregnanolone suppresses mechanical allodynia and internalization of
      neurokinin-1 receptors at the spinal dorsal horn in a rat postoperative pain
      model.
AB  - Background: To identify a new strategy for postoperative pain management, we
      investigated the analgesic effects of allopregnanolone (Allo) in an incisional
      pain model, and also assessed its effects on the activities of the primary
      afferent fibers at the dorsal horn. Methods: In experiment 1, 45 rats were
      assigned to Control, Allo small-dose (0.16 mg/kg), and Allo large-dose (1.6
      mg/kg) groups (n = 15 in each). The weight bearing and mechanical withdrawal
      thresholds of the hind limb were measured before and at 2, 24, 48, and 168 h
      after Brennan's surgery. In experiment 2, 16 rats were assigned to Control and
      Allo (0.16 mg/kg) groups (n = 8 in each). The degree of spontaneous pain was
      measured using the grimace scale after the surgery. Activities of the primary
      afferent fibers in the spinal cord (L6) were evaluated using immunohistochemical
      staining. Results: In experiment 1, the withdrawal threshold of the Allo small
      dose group was significantly higher than that of the Control group at 2 h after
      surgery. Intergroup differences in weight bearing were not significant. In
      experiment 2, intergroup differences in the grimace scale scores were not
      significant. Substance P release in the Allo (0.16 mg/kg) group was significantly
      lower than that in the Control group. Conclusions: Systemic administration of
      Allo inhibited mechanical allodynia and activities of the primary afferent fibers
      at the dorsal horn in a rat postoperative pain model. Allo was proposed as a
      candidate for postoperative pain management.

PMID- 29372022
TI  - Neuroticism and pain catastrophizing aggravate response to pain in healthy
      adults: an experimental study.
AB  - Background: The aim of this study was to investigate the association between
      neuroticism, pain catastrophizing, and experimentally induced pain threshold and
      pain tolerance in a healthy adult sample from two regions of the country of
      Croatia: the island of Korcula and city of Split. Methods: A total of 1,322
      participants were enrolled from the Island of Korcula (n = 824) and the city of
      Split (n = 498). Participants completed a self-reported personality measure
      Eysenck Personality Questionnaire (EPQ) and pain catastrophizing questionnaire
      Pain Catastrophizing Scale (PCS), followed by a mechanical pain pressure
      threshold and tolerance test. We have explored the mediating role of
      catastrophizing in the relationship between neuroticism and pain intensity.
      Results: The results showed that pain catastrophizing partially mediated the
      relationship between neuroticism and pain intensity, suggesting the importance of
      pain catastrophizing in increasing vulnerability to pain. The results also
      indicated gender-related differences, marked by the higher pain threshold and
      tolerance in men. Conclusions: This study adds to the understanding of the
      complex interplay between personality and pain, by providing a better
      understanding of such mechanisms in healthy adults.

PMID- 29372024
TI  - Double blind randomized control trial to evaluate the efficacy of ketoprofen
      patch to attenuate pain during venous cannulation.
AB  - Background: Venipuncture pain is an uncomfortable suffering to the patient. It
      creates anxiety, fear and dissatisfaction. The ketoprofen transdermal patch is a
      proven treatment for musculoskeletal and arthritic pain. We planned this study to
      evaluate the efficacy of the ketoprofen patch to reduce venipuncture pain.
      Methods: Two hundred adult patients, aged 18-60 years, of either sex, ASA grade I
      or II, were enrolled. Presuming that therapy would decrease venipuncture pain by
      30%, a power calculation with alpha = 0.05 and beta = 0.80 required enrollment of
      at least 24 patients into each group. However, 100 patients in each group were
      recruited. Group I (Control) received a placebo patch; Group II (Ketoprofen)
      received a 20 mg ketoprofen patch. A selected vein on the dorsum of the patient's
      non-dominant hand was cannulated with 18 g intravenous cannula 1 h after the
      application of the respective patch. Assessment of pain was done by a 10 cm
      visual analogue scale (VAS) of 0-10, where 0 depicts "no pain" and 10 is "the
      worst imaginable pain". The venipuncture site was assessed for the presence of
      skin erythema, swelling and rashes at 12 h, 24 h and at the time of
      decannulation. Results: Incidence of pain was 100% (94/94) in the control group
      as compared to 93% (85/91) in the ketoprofen group. The severity of the
      venipuncture pain was 6 (2) and 2 (2) for control and ketoprofen groups
      respectively (P < 0.05). Conclusions: Application of a ketoprofen patch at the
      proposed site of venipuncture one hour before the attempt is effective and safe
      for attenuating venipuncture pain.

PMID- 29372023
TI  - Therapeutic lumbar facet joint nerve blocks in the treatment of chronic low back
      pain: cost utility analysis based on a randomized controlled trial.
AB  - Background: Related to escalating health care costs and the questionable
      effectiveness of multiple interventions including lumbar facet joint
      interventions, cost effectiveness or cost utility analysis has become the
      cornerstone of evidence-based medicine influencing coverage decisions. Methods:
      Cost utility of therapeutic lumbar facet joint nerve blocks in managing chronic
      low back pain was performed utilizing data from a randomized, double-blind,
      controlled trial with a 2-year follow-up, with direct payment data from 2016.
      Based on the data from surgical interventions, utilizing the lowest proportion of
      direct procedural costs of 60%, total cost utility per quality adjusted life year
      (QALY) was determined by multiplying the derived direct cost at 1.67. Results:
      Patients in this trial on average received 5.6 +/- 2.6 procedures over a period
      of 2 years, with average relief over a period of 2 years of 82.8 +/- 29.6 weeks
      with 19 +/- 18.77 weeks of improvement per procedure. Procedural cost for one
      year improvement in quality of life showed USD $2,654.08. Estimated total costs,
      including indirect costs and drugs with multiplication of direct costs at 1.67,
      showed a cost of USD $4,432 per QALY. Conclusions: The analysis of therapeutic
      lumbar facet joint nerve blocks in the treatment of chronic low back pain shows
      clinical effectiveness and cost utility at USD $2,654.08 for the direct costs of
      the procedures, and USD $4,432 for the estimated overall cost per one year of
      QALY, in chronic persistent low back pain non-responsive to conservative
      management.

PMID- 29372025
TI  - Cytotoxic activity and subset populations of peripheral blood natural killer
      cells in patients with chronic pain.
AB  - Background: Chronic pain reportedly exerts complex effects on immune function.
      Natural killer (NK) cells are lymphocytes that play a critical role in cellular
      and innate immunity. This study examined changes in the subset populations and
      cytotoxic activity of peripheral blood NK cells in patients with chronic pain.
      Methods: Thirty patients with chronic moderate-to-severe pain (group P) and age
      matched pain-free subjects (group NoP) were enrolled. Peripheral whole blood was
      analyzed for the percentage and expression of NK cell surface markers (CD56 and
      CD16) by flow cytometry. Cytotoxic activity was assayed by evaluating CD69
      expression on CD3-/CD56+NK cells. Results: The percentage of NK cells among total
      lymphocytes was not significantly different between groups P and NoP (16.3 +/-
      9.3 vs. 20.2 +/- 10.5%). Likewise, the percentages of two major NK cell subsets,
      CD56bright and CD56dim, were also not significantly different between the two
      groups. However, the percentage of CD56bright/CD16+ subset, was slightly but
      significantly increased in group P (1.0 +/- 0.9%; P < 0.01) compared with group
      NoP (0.5 +/- 0.6%). The cytotoxicity of NK cells was not different between the
      two groups, showing similar CD69 expression (P vs. NoP = 29.2 +/- 15.2 vs. 32.0
      +/- 15.0%). These findings were not influenced by pain intensity, opioid use, or
      disease causing pain in group P. Conclusions: NK cell cytotoxic activity and
      major subset populations, with the exception of an increased percentage of the
      CD56bright/CD16+ subset, are not significantly altered in patients with chronic
      severe pain.

PMID- 29372026
TI  - Transient paraplegia after neurolytic splanchnic block in a patient with
      metastatic colon carcinoma.
AB  - We present a patient with metastatic colon carcinoma who developed paraplegia
      following a neurolytic splanchnic block. A 41-year old man with metastatic
      adenocarcinoma of the colon received a splanchnic neurolytic block using alcohol
      because of severe abdominal pain. Bilateral motor weakness and a sensorial
      deficit in both legs developed after the procedure. Diffusion magnetic resonance
      imaging revealed spinal cord ischemia between T8 and L1. The motor and sensorial
      deficits were almost completely resolved at the end of the third month. We think
      that anterior spinal artery syndrome due to reversible spasms of the lumbar
      radicular arteries using alcohol have resulted in transient paraplegia. The
      retrograde spread of alcohol to neural structures may have also contributed.

PMID- 29372027
TI  - Lumbar burner and stinger syndrome in an elderly athlete.
AB  - Burner or stinger syndrome is a rare sports injury caused by direct or indirect
      trauma during high-speed or contact sports mainly in young athletes. It affects
      peripheral nerves, plexus trunks or spinal nerve roots, causing paralysis,
      paresthesia and pain. We report the case of a 57-year-old male athlete suffering
      from burner syndrome related to a lumbar nerve root. He presented with prolonged
      pain and partial paralysis of the right leg after a skewed landing during the
      long jump. He was initially misdiagnosed since the first magnet resonance imaging
      was normal whereas electromyography showed denervation. The insurance company
      refused to pay damage claims. Partial recovery was achieved by pain medication
      and physiotherapy. Burner syndrome is an injury of physically active individuals
      of any age and may appear in the cervical and lumbar area. MRI may be normal due
      to the lack of complete nerve transection, but electromyography typically shows
      pathologic results.

PMID- 29372028
TI  - Pain in beta-thalassemia major patients: an important yet neglected issue.

PMID- 29372029
TI  - Iranian Journal of Basic Medical Sciences comes of age on the 20th anniversary of
      publication.

PMID- 29372030
TI  - Changes in expression of klotho affect physiological processes, diseases, and
      cancer.
AB  - Klotho (KL) encodes a single-pass transmembrane protein and is predominantly
      expressed in the kidney, parathyroid glands, and choroid plexus. Genetic studies
      on the KL gene have revealed that DNA hypermethylation is one of the major risk
      factors for aging, diseases, and cancer. Besides, KL exerts anti-inflammatory and
      anti-tumor effects by regulating signaling pathways and the expression of target
      genes. KL participates in modulation of the insulin/insulin-like growth factor-1
      (IGF-1) signaling, which induces the growth hormone (GH) secretion. Accordingly,
      KL mutant mice display multiple aging-like phenotypes, which are ameliorated by
      overexpression of KL. Therefore, KL is an important contributor to lifespan. KL
      is further identified as a regulator of calcium (Ca2+) channel-dependent cell
      physiological processes. KL has been also shown to induce cancer cell apoptosis,
      thus, it is considered as a potential tumor suppressor. Our recent studies have
      indicated that KL modulates an influx of Ca2+ from the extracellular space,
      leading to a change in CCL21-dependent migration in dendritic cells (DCs).
      Interestingly, the regulation of the expression of KL was mediated through a
      phosphoinositide 3-kinase (PI3K) pathway in DCs. Moreover, downregulating of KL
      expression by using siRNA knockdown technique, we observed that the expression of
      Ca2+ channels including Orai3, but not Orai1, Orai2, TRPV5 and TRPV6 was
      significantly reduced in KL-silenced as compared to control BMDCs. Clearly,
      additional research is required to define the role of KL in the regulation of
      organismic and cellular functions through the PI3K signaling and the expression
      of the Ca2+ channels.

PMID- 29372031
TI  - Design, synthesis, and biological evaluation of 6-methoxy-2-arylquinolines as
      potential P-glycoprotein inhibitors.
AB  - Objectives: In the present study, a new series of 6-methoxy-2-arylquinoline
      analogues was designed and synthesized as P-glycoprotein (P-gp) inhibitors using
      quinine and flavones as the lead compounds. Materials and Methods: The cytotoxic
      activity of the synthesized compounds was evaluated against two human cancer cell
      lines including EPG85-257RDB, multidrug-resistant gastric carcinoma cells (P-gp
      positive gastric carcinoma cell line), and EPG85-257P, drug-sensitive gastric
      carcinoma cells. Compounds showing low to moderate toxicity in the MTT test were
      selected to investigate their P-gp inhibition activity. Moreover, trying to
      explain the results of biological experiments, docking studies of the selected
      compounds into the homology-modeled human P-gp, were carried out. The
      physicochemical and ADME properties of the compounds as drug candidate were also
      predicted. Results: Most of our compounds exhibited negligible or much lower
      cytotoxic effect in both cancer cells. Among the series, 5a and 5b, alcoholic
      quinoline derivatives were found to inhibit the efflux of rhodamine 123 at the
      concentration of 10 MUM significantly. Conclusion: Among the tested quinolines,
      5a and 5b showed the most potent P-gp inhibitory activity in the series and were
      1.3-fold and 2.1-fold stronger than verapamil, respectively. SAR data revealed
      that hydroxyl methyl in position 4 of quinolines has a key role in P-gp efflux
      inhibition of our compounds. ADME studies suggested that all of the compounds
      included in this study may have a good human intestinal absorption.

PMID- 29372032
TI  - Protective effect of metformin on D-galactose-induced aging model in mice.
AB  - Objectives: Metformin (Met), an antidiabetic biguanide, reduces hyperglycemia via
      improving glucose utilization and reducing the gluconeogenesis. Met has been
      shown to exert neuroprotective, antioxidant and anti-inflammatory properties. The
      present study investigated the possible effect of Met on the D-galactose (D-gal)
      induced aging in mice. Materials and Methods: Met (1 and 10 mg/kg/p.o.), was
      administrated daily in D-gal-received (500 mg/kg/p.o.) mice model of aging for
      six weeks. Anxiety-like behavior, cognitive function, and physical power were
      evaluated by the elevated plus-maze, novel object recognition task (NORT), and
      forced swimming capacity test, respectively. The brains were analyzed for the
      level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF).
      Results: Met decreased the anxiety-like behavior in D-gal-treated mice. Also, Met
      treated mice showed significantly improved learning and memory ability in NORT
      compared to the D-gal-treated mice. Furthermore, Met increased the physical power
      as well as the activity of SOD and BDNF level in D-gal-treated mice. Conclusion:
      Our results suggest that the use of Met can be an effective strategy for
      prevention and treatment of D-gal-induced aging in animal models. This effect
      seems to be mediated by attenuation of oxidative stress and enhancement of the
      neurotrophic factors.

PMID- 29372033
TI  - Immunogenicity of chimeric MUC1-HER2 vaccine against breast cancer in mice.
AB  - Objectives: Breast cancer is one of the most common cancers in the world and is
      on the increase. MUC1 and HER2 as tumor-associated antigens (TAAs) are abnormally
      expressed to some extent in 75-80% of breast cancers. In our present research, a
      novel chimeric MUC1-HER2 (HM) protein was designed and used to study whether an
      immune response can be generated against these TAAs. In vitro analysis of the
      HER2-MUC1 construct confirmed the co-expression of MUC1 and HER2. Materials and
      Methods: BALB/c mice were immunized with this novel chimeric protein. The humoral
      immune response was assessed by enzyme-linked immunosorbent assay (ELISA). Then,
      BALB/c mice were injected subcutaneously 2*105 4T1-MUC1-HER2 tumor cells.
      Subsequently, tumor size and tumor necrosis measurements, MTT, cytokines assay
      and survival test were performed. Results: The results implied a critical role of
      HER2 and MUC1 antibodies in vaccination against breast cancer. This engineered
      protein can be a good vaccine to stop breast cancer. Conclusion: The results
      implied a critical role of HER2 and MUC1 antibodies in vaccination against breast
      cancer. This engineered protein can be a good vaccine to stop breast cancer.

PMID- 29372034
TI  - Protosappanin A protects against atherosclerosis via anti- hyperlipidemia, anti
      inflammation and NF-kappaB signaling pathway in hyperlipidemic rabbits.
AB  - Objectives: Protosappanin A (PrA) is an effective and major ingredient of
      Caesalpinia sappan L. The current study was aimed to explore the effect of PrA on
      atherosclerosis (AS). Materials and Methods: Firstly, the experimental model of
      AS was established in rabbits by two-month feeding of high fat diet. Then, the
      rabbits were randomly divided into five groups and treated with continuous high
      lipid diet (model control), high lipid diet containing rosuvastatin (positive
      control), 5 mg/kg PrA (low dose) or 25 mg/kg PrA (high dose). Results: Our
      results showed that PrA markedly alleviated AS as indicated by hematoxylin/eosin
      (HE) staining. PrA also reduced hyperlipidemia (as demonstrated by the serum
      levels of total blood cholesterol (TC), triglyceride (TG), low-density
      lipoprotein (LDL) and high-density lipoprotein (HDL)) in a time and dose
      dependent manner, and decreased inflammation (as indicated by the serum levels of
      matrix metalloproteinase-9 [MMP-9], interleukin-6 [IL-6] and tumor necrosis
      factor-alpha [TNF-alpha]). Moreover, PrA significantly inactivated nuclear factor
      kappa B (NF-kappaB) signaling as indicated by nuclear NF-kappaB p65 protein
      expression, as well as the mRNA expression and serum levels of downstream genes,
      interferon-gamma (IFN-gamma) and interferon-gamma-inducible protein 10 (IP10).
      Conclusion: This study proved that PrA might protect against atherosclerosis via
      anti-hyperlipidemia, anti-inflammation and NF-kappaB signaling pathways in
      hyperlipidemic rabbits.

PMID- 29372035
TI  - The toxicity study of synthesized inverse carnosine peptide analogues on HepG2
      and HT-29 cells.
AB  - Objective: Cancer has risen as the main cause of diseases with the highest rate
      of mortality in the world. Drugs used in cancer, usually demonstrate side effects
      on normal tissues. On the other hand, anticancer small peptides, effective on
      target tissues, should be safe on healthy organs, as being naturally originated
      compounds. In addition, they may have good pharmacokinetic properties. carnosine,
      a natural dipeptide, has shown many biological functions, including anti-oxidant,
      anti-senescence, anti-inflammatory and anticancer activities. This study, with
      the aim of introducing new anticancer agents with better properties, is focused
      on the synthesis and cytotoxic evaluation of some peptide analogues of carnosine.
      Materials and Methods: The cytotoxic activity of the synthesized peptides,
      prepared by the solid-phase peptide synthesis method, was evaluated against two
      cell lines of HepG2 and HT-29 using MTT assay, lactate dehydrogenase (LDH) assay
      and flow cytometry analysis. Results: Linear and cyclic analogues of carnosine
      peptide showed cytotoxicity, demonstrated by several experiments, against HepG2
      and HT-29 cell lines with mean IC50 values ranging from 9.81 to 16.23 ug/ml.
      Among the peptides, compounds 1c, 3c and 6b (linear analogue of 3c) showed a
      considerable toxic activity on the cancerous cell lines. Conclusion: The cyclic
      peptide analogues of carnosine with His-beta-Ala-Pro-beta-Ala-His (1c) and beta
      Ala-His-Pro-His-beta-Ala (3c) sequences showed cytotoxic activity on cancerous
      cells of HepG2 and HT-29, better than carnosine, and thus can be good candidates
      to develop new anticancer agents. The mechanism of cytotoxicity may be through
      cell apoptosis.

PMID- 29372036
TI  - Histomorphometric evaluation of mice testicular tissue following short- and long
      term effects of lipopolysaccharide-induced endotoxemia.
AB  - Objectives: Lipopolysaccharide (LPS)-induced endotoxemia is known to cause male
      infertility. This study was designed to explore the effects of bacterial LPS on
      histomorphometric changes of mice testicular tissues. Materials and Methods: In
      experiment 1, a pilot dose responsive study was performed with mice that were
      divided into five groups, receiving 36000, 18000, 9000, and 6750 ug/kg body
      weight (B.W) of LPS or only saline (control). White blood cells (WBC) were
      observed for 3 days after LPS inoculation. In experiment 2, two groups of mice
      were treated with 6750 ug/kg B.W of LPS or only saline (control). Five cases from
      each experimental group were sacrificed at 3, 30, and 60 days after LPS
      inoculation. Left testes were fixed in Bouin's solution, and stained for
      morphometrical assays. Results: Time-course changes of WBC obtained from
      different doses of LPS-treated mice showed that inoculation of 6750 ug/kg B.W
      produced a reversible endotoxemia that lasts for 72 hr and so it was used in the
      second experiment. In experiment 2, during the first 3 days, no significant
      changes were observed in the evaluated parameters instead of seminiferous tubules
      diameter. Spermatogenesis, Johnsen's score, meiotic index, and epithelial height
      were significantly affected at 30th day. However, complete recovery was only
      observed for the spermatogenesis at day 60. Interestingly, deleterious effects of
      LPS on spermatogonia were only seen at 60th day (P<0.05). Conclusion: Endotoxemia
      induced by LPS has long-term detrimental effects on spermatogonia and later stage
      germ cells, which are reversible at the next spermatogenic cycle.

PMID- 29372037
TI  - Neuroprotective effect of berberine chloride on cognitive impairment and
      hippocampal damage in experimental model of vascular dementia.
AB  - Objectives: The major objective of the present study was to investigate the
      potential neuroprotective effect of berberine chloride on vascular dementia.
      Berberine, as an ancient medicine in China and India, is the main active
      component derived from the Berberis sp. Several studies have revealed the
      beneficial effects of berberine in various neurodegenerative disorders. Materials
      and Methods: To induce vascular dementia, chronic bilateral common carotid artery
      occlusion was performed on male Wistar rats. After surgery, the rats were treated
      daily by oral administration of berberine chloride (50 mg/kg) for two months. The
      cognition function of treated rats, were evaluated by Morris Water Maze (MWM)
      test. In addition, Nissl and TUNEL staining were chosen to assess neuronal damage
      within the hippocampal CA1 area. Results: It was obvious that chronic cerebral
      hypoperfusion (CCH), caused cognitive impairment and neuronal damages within CA1
      hippocampal subregion. Berberine chloride was able to prevent cognitive deficits,
      (P<0.05) and reversed CCH-induced hippocampal neuronal loss and apoptosis,
      (P<0.05). Conclusion: Berberine chloride may be considered as a potential
      treatment for cognitive deficits and neuronal injury caused by CCH in the
      hippocampal CA1 area.

PMID- 29372038
TI  - Metabolomics diagnostic approach to mustard airway diseases: a preliminary study.
AB  - Objectives: This study aims to evaluate combined proton nuclear magnetic
      resonance (1H NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)
      metabolic profiling approaches, for discriminating between mustard airway
      diseases (MADs) and healthy controls and for providing biochemical information on
      this disease. Materials and Methods: In the present study, analysis of serum
      samples collected from 17 MAD subjects and 12 healthy controls was performed
      using NMR. Of these subjects, 14 (8 patients and 6 controls) were analyzed by GC
      MS. Then, their spectral profiles were subjected to principal component analysis
      (PCA) and orthogonal partial least squares regression discriminant analysis (OPLS
      DA). Results: A panel of twenty eight metabolite biomarkers was generated for
      MADs, sixteen NMR-derived metabolites (3-methyl-2-oxovaleric acid, 3
      hydroxyisobutyrate, lactic acid, lysine, glutamic acid, proline, hydroxyproline,
      dimethylamine, creatine, citrulline, choline, acetic acid, acetoacetate,
      cholesterol, alanine, and lipid (mainly VLDL)) and twelve GC-MS-derived
      metabolites (threonine, phenylalanine, citric acid, myristic acid, pentadecanoic
      acid, tyrosine, arachidonic acid, lactic acid, propionic acid, 3-hydroxybutyric
      acid, linoleic acid, and oleic acid). This composite biomarker panel could
      effectively discriminate MAD subjects from healthy controls, achieving an area
      under receiver operating characteristic curve (AUC) values of 1 and 0.79 for NMR
      and GC-MS, respectively. Conclusion: In the present study, a robust panel of
      twenty-eight biomarkers for detecting MADs was established. This panel is
      involved in three metabolic pathways including aminoacyl-tRNA biosynthesis,
      arginine, and proline metabolism, and synthesis and degradation of ketone bodies,
      and could differentiate MAD subjects from healthy controls with a higher
      accuracy.

PMID- 29372039
TI  - Monitoring wound healing of burn in rat model using human Wharton's jelly
      mesenchymal stem cells containing cGFP integrated by lentiviral vectors.
AB  - Objectives: Human Wharton's Jelly mesenchymal stem cells (hWMSCs) are
      undifferentiated cells commonly used in regenerative medicine. The aim of this
      study was to develop a reliable tool for tracking hWMSCs when utilized as
      therapeutics in burnt disorders and also to optimize the cell-based treatment
      procedure. Materials and Methods: The hWMSCs were first isolated from fresh
      umbilical cord Wharton's jelly and cultured. The 293LTV cell line was transfected
      by cGFP containing lentiviral vector and the helper plasmids for production of
      the viral particle. The viral particles were collected to transduce the hWMSCs.
      The transduced cells were finally selected based on resistance to puromycin. The
      burned rats (n=24) were treated with cGFP expressing hWMSCs using the cell spray
      method, with the cells being tracked 7, 14 and 21 days later. The rats were
      sacrificed 7, 14 and 21 days following treatment and paraffin embedded sections
      prepared from the burned area for downstream pathological analyses. Results: The
      lentiviral particles carrying the cGFP gene were generated and the hWMSCs were
      transduced. The cGFP-expressing hWMSCs were detected in the burned tissue and the
      burned injuries were improved dramatically as compared to control. Conclusion:
      Because of the establishment of stably transduced cGFP expressing cells and the
      ability to detect cGFP for a relatively long-time interval, the method was found
      to be quite efficient for the purpose of cell tracking. The combination of hWMSC
      based cell therapy and sterile Gauze Vaseline (GV) as covering was proven much
      more efficient than the traditional methods based on GV alone.

PMID- 29372040
TI  - 99mTc-Glucarate for assessment of paclitaxel therapy in human ovarian cancer in
      mice.
AB  - Objectives: The monitoring of cancer treatment response to chemotherapy is
      considered an essential strategy for follow-up of patients. The aim of this study
      was to evaluate the use of 99mTc-glucarate as a radiotracer for in vivo
      quantification and visualization of necrotic area and therapeutic effect of
      paclitaxel in ovarian cancer xenografted nude mice. Materials and Methods: After
      implantation of human ovarian cancer (SKOV-3) in nude mice, tumor xenografted
      mice were enrolled in two groups as control and treatment (paclitaxel) groups.
      99mTc-glucarate uptakes were quantified in tumors of control and treatment groups
      and also tumor imaging was performed with a gamma camera. The necrotic and viable
      areas of tumor and tumoral masses were evaluated through histopathological and
      macroscopic observations, respectively. Results: 99mTc-glucarate uptake in tumor
      of treatment group was higher than control group.99mTc-glucarate uptake in
      ovarian tumor was clearly visualized with gamma imaging in both groups, but
      paclitaxel treated group showed higher radioactive uptake than control mice. The
      necrotic area in tumoral mass of mice treated with paclitaxel was confirmed by
      histopathological observations. Conclusion: 99mTc-glucarate is an effective
      radiotracer for evaluation and monitoring of tumor necrosis caused by
      chemotherapy, and it may be helpful for therapy monitoring in patients with
      cancer.

PMID- 29372041
TI  - Tanshinone IIA inhibits AGEs-induced proliferation and migration of cultured
      vascular smooth muscle cells by suppressing ERK1/2 MAPK signaling.
AB  - Objectives: Vascular smooth muscle cells (VSMCs) play a key role in the
      pathogenesis of diabetic vascular disease. Our current study sought to explore
      the effects of tanshinone IIA on the proliferation and migration of VSMCs induced
      by advanced glycation end products (AGEs). Materials and Methods: In this study,
      we examined the effects of tanshinone IIA by cell proliferation assay and cell
      migration assay. And we explored the underlying mechanism by Western blotting.
      Results: AGEs significantly induced the proliferation and migration of VSMCs, but
      treatment with tanshinone IIA attenuated these effects. AGEs could increase the
      activity of the ERK1/2 and p38 pathways but not the JNK pathway. Treatment with
      tanshinone IIA inhibited the AGEs-induced activation of the ERK1/2 pathway but
      not the p38 pathway. Conclusion: Tanshinone IIA inhibits AGEs-induced
      proliferation and migration of VSMCs by suppressing the ERK1/2 MAPK signaling
      pathway.

PMID- 29372042
TI  - Intrauterine xenotransplantation of human Wharton jelly-derived mesenchymal stem
      cells into the liver of rabbit fetuses: A preliminary study for in vivo
      expression of the human liver genes.
AB  - Objectives: End-stage hepatic failure is a potentially life-threatening condition
      for which orthotopic liver transplantation is the only effective treatment.
      However, a shortage of available donor organs for transplantation each year
      results in the death of many patients waiting for liver transplantation.
      Xenotransplantation, or the transplantation of cells, tissues, or organs between
      different species, was proposed as a possible solution to the worldwide shortage
      of human organs and tissues for transplantation. The purpose of this preliminary
      study was to reconstruct human liver tissue by xenotransplantation of human
      Wharton jelly mesenchymal stem cells (hWJ-MSCs) into fetal rabbit. Materials and
      Methods: Isolation and confirmation of hWJ-MSCs from human umbilical cord was
      performed. Eight rabbits at gestational day 14 were anesthetized. All rabbits
      carried pregnancies to term yielding 40 rabbit fetuses. Intrauterine injection of
      hWJ-MSCs was performed in 24 fetuses. Twenty-seven fetuses were born alive. Ten
      liver samples from injected fetuses were sampled, eight rabbits 3 days after
      birth and two rabbits 21 days after birth. The non-injected fetuses served as
      positive control. Fetuses of non-injected rabbits were negative controls. Using
      real-time polymerase chain reaction (RT-PCR), mRNA expression of albumin (ALB),
      alpha-fetoprotein (AFP), hepatic nuclear factor 4 (HNF4), and CYP2B6 (CYP) were
      detected in liver samples. Results: The human ALB, AFP, HNF4, and CYP mRNAs were
      expressed in the injected sampled fetuses by hWJ-MSCs into fetuses of rabbits in
      utero. Conclusion: Developing xenotransplantation of hWJ-MSCs into rabbit uterus
      can introduce an applied approach for producing human liver tissue in rabbits.

PMID- 29372043
TI  - Mast cells and pro-inflammatory cytokines roles in assessment of grape seeds
      extract anti-inflammatory activity in rat model of carrageenan-induced paw edema.
AB  - Objectives: Reactive oxygen species (ROS)-produced oxidative disorders were
      involved at the pathophysiology of many inflammatory processes via the generation
      of pro-inflammatory cytokines and antioxidant defense system suppression.
      Although herbal antioxidants as mono-therapy relief many inflammatory diseases
      including, autoimmunity rheumatoid arthritis, but as combination therapy with
      other proven anti-inflammatory drugs in order to decreasing their toxic impacts
      has not yet been studied clearly, especially against chemical substances that's
      induced local inflammation with characteristic edema. Materials and Methods:
      Grape seeds extract (GSE) at a concentration of 40 mg/kg B. wt alone or in
      combination with indomethacin (Indo.) at a dose of 5 mg/Kg B. wt orally given for
      10 days prior (gps VI, VII, VIII) or as a single dose after edema induction (gps
      IX, X, XI) in rat's left hind paw by sub-planter single injection of 0.1
      carrageenan: saline solution (1%) (gp. V) to assess the prophylactic and
      therapeutic anti-inflammatory activities of both through the estimation of
      selective inflammatory mediators and oxidative damage-related biomarkers as well
      as tissue mast cell scoring. Furthermore, both substances were given alone (gps
      II, III, IV) for their blood, liver and kidney safety evaluation comparing with
      negative control rats (gp. I) which kept without medication. Results: A marked
      reduction on the inflammatory mediators, edema volume and oxidative byproducts in
      edema bearing rats' prophylactic and treated with grape seeds extract and
      indomethacin was observed. Indomethacin found to induce some toxicological
      impacts which minimized when administered together with GSE. Conclusion: GSE is a
      safe antioxidant agent with anti-inflammatory property.

PMID- 29372044
TI  - Novel frameshift mutation in the KCNQ1 gene responsible for Jervell and Lange
      Nielsen syndrome.
AB  - Objectives: Jervell and Lange-Nielsen syndrome is an autosomal recessive disorder
      caused by mutations in KCNQ1 or KCNE1 genes. The disease is characterized by
      sensorineural hearing loss and long QT syndrome. Materials and Methods: Here we
      present a 3.5-year-old female patient, an offspring of consanguineous marriage,
      who had a history of recurrent syncope and congenital sensorineural deafness. The
      patient and the family members were screened for mutations in KCNQ1 gene by
      linkage analysis and DNA sequencing. Results: DNA sequencing showed a
      c.1532_1534delG (p. A512Pfs*81) mutation in the KCNQ1 gene in homozygous form.
      The results of short tandem repeat (STR) markers showed that the disease in the
      family is linked to the KCNQ1 gene. The mutation was confirmed in the parents in
      heterozygous form. Conclusion: This is the first report of this variant in KCNQ1
      gene in an Iranian family. The data of this study could be used for early
      diagnosis of the condition in the family and genetic counseling.

PMID- 29372045
TI  - Spore liberation in mosses revisited.
AB  - The ability to perform hygroscopic movements has evolved in many plant lineages
      and relates to a multitude of different functions such as seed burial, flower
      protection or regulation of diaspore release. In most mosses, spore release is
      controlled by hygroscopic movements of the peristome teeth and also of the spore
      capsule. Our study presents, for the first time, temporally and spatially well
      resolved kinematic analyses of these complex shape changes in response to
      humidity conditions and provides insights into the sophisticated functional
      morphology and anatomy of the peristome teeth. In Brachythecium populeum the
      outer teeth of the peristome perform particularly complex hygroscopic movements
      during hydration and desiccation. Hydration induces fast inward dipping followed
      by partial re-straightening of the teeth. In their final shape, wet teeth close
      the capsule. During desiccation, the teeth perform an outward flicking followed
      by a re-straightening which opens the capsule. We present a kinematic analysis of
      these shape changes and of the underlying functional anatomy of the teeth. These
      teeth are shown to be composed of two layers which show longitudinal gradients in
      their material composition, structure and geometry. We hypothesize that these
      gradients result in (i) differences in swelling/shrinking capacity and velocity
      between the two layers composing the teeth, and in (ii) a gradient of velocity of
      swelling and shrinking from the tip to the base of the teeth. We propose these
      processes explain the observed movements regulating capsule opening or closing.
      This hypothesis is corroborated by experiments with isolated layers of peristome
      teeth. During hydration and desiccation, changes to the shape and mass of the
      whole spore capsule accompany the opening and closing. Results are discussed in
      relation to their significance for humidity-based regulation of spore release.

PMID- 29372046
TI  - The schism in chiropractic through the eyes of a 1st year chiropractic student.
AB  - Since its inception, the chiropractic profession has been divided along
      ideological fault lines. These divisions have led to a profession wide schism,
      which has limited mainstream acceptance, utilisation, social authority and
      integration. The authors explore the historical origins of this schism, taking
      time to consider historical context, religiosity, perpetuating factors, logical
      fallacies and siege mentality. Evidence is then provided for a way forward, based
      on the positioning of chiropractors as mainstream partners in health care.

PMID- 29372047
TI  - Prevalence and risk factors for hyperthyroidism in Irish cats from the greater
      Dublin area.
AB  - Background: Hyperthyroidism is common in older cats. Prevalence varies
      geographically, but is anecdotally considered low in Ireland. The aim of this
      study was to document prevalence of hyperthyroidism in older cats in the greater
      Dublin area of Ireland and to assess environmental and clinical associations for
      development and identification of the disease. Methods: Primary-care veterinary
      practices were requested to select cats aged 10 years or older where blood
      sampling was being performed for health screening or clinical investigations.
      Surplus serum/plasma samples were submitted to University College Dublin
      Diagnostic Endocrine Laboratory for total thyroxine (T4) measurement. Cats were
      classified as hyperthyroid, equivocal or euthyroid based on a total T4
      concentration (reference interval, 15-60 nmol/L), of >60 nmol/L, 30-60 nmol/L or
      <30 nmol/L, respectively. Simultaneous free T4 or repeat (after 4-6 weeks) total
      T4 measurement was recommended in all equivocal cases. Animals receiving
      treatment for hyperthyroidism were excluded. A questionnaire completed by the
      client and veterinarian detailing historical and physical information was also
      required. Associations between categorical variables were analysed by Chi-square
      or Fisher's exact test and odds ratio (OR) calculated. A P value of <0.05 was
      considered statistically significant. Results: Samples were submitted from 507
      cats including 107 (21.1%) hyperthyroid, 54 (10.6%) equivocal and 346 (68.2%)
      euthyroid. The presence of goitre (P < 0.0001), tachypnoea (P = 0.0378),
      tachycardia (P = 0.002), polyphagia (P = 0.0003) and weight loss (P < 0.0001)
      were significantly associated with hyperthyroidism. Cats with goitre were more
      likely to be diagnosed as hyperthyroid [OR 2.85, (95% CI 1.75-4.62] compared to
      those without. However, goitre was only palpated in 40 of 102 (39.2%)
      hyperthyroid cats. Increasing age was the only significant (P < 0.002) risk
      factor for development of hyperthyroidism. A relationship between hyperthyroidism
      and sex, breed, lifestyle, parasite control, vaccination status or feeding habits
      was not identified. Conclusions: Hyperthyroidism is not uncommon in Irish cats.
      Age was the only significant risk factor for its development. The high proportion
      of hyperthyroid cats without palpable goitre (> 60%) may reflect failure to
      detect goitre and account for the perceived low prevalence of this condition in
      Ireland.

PMID- 29372049
TI  - Open Access publishing: the continuing development of the Journal of Nutritional
      Science.

PMID- 29372048
TI  - Prevalence and characterization of Salmonella in two integrated broiler
      operations in Korea.
AB  - Background: Vertical integration of the broiler industry allows producers to
      combine different biosecurity and sanitation practices, housing technologies, and
      feeding regimens to improve food safety. The purpose of this study was to
      investigate the prevalence and distribution of Salmonella, to determine the
      source of Salmonella contaminants, and to reveal the relationships between
      isolates at each step in the vertically integrated broiler production system in
      two representative integrated broiler companies in Korea. Results: A total of
      2148 samples were collected from 2 broiler breeder hatcheries, 14 broiler breeder
      farms, 3 broiler hatcheries, 16 broiler farms, 8 broiler transporting trucks and
      6 slaughterhouses belonging to representative integrated broiler companies, and
      205 (9.5%) of these samples were positive for Salmonella. The Salmonella
      prevalence in broiler hatcheries (34.0%) and broiler transporting trucks (62.5%)
      was higher (P < 0.05) whereas that in the broiler breeder hatchery (0.8%) was
      lower (P < 0.05), than the overall prevalence. Nine and 13 different Salmonella
      serotypes were isolated from integrated companies A and B, and the predominant
      serotypes were S. Virchow (39.7%) and S. Hadar (59.2%), respectively. Pulsed
      field gel electrophoresis patterns of isolates from the two operations showed
      significant genetic relatedness within a single system. Conclusions: In a
      comparison of the two operations that participated in this study, the prevalence
      of Salmonella differed significantly between the broiler breeder hatchery, and
      broiler hatcheries and broiler farms.

PMID- 29372050
TI  - Improvement of glucose and lipid metabolism via mung bean protein consumption:
      clinical trials of GLUCODIATM isolated mung bean protein in the USA and Canada.
AB  - The aim of the present study was to confirm the effects of a commercially
      available mung bean protein isolate (GLUCODIATM) on glucose and lipid metabolism.
      The main component of GLUCODIATM is 8S globulin, which constitutes 80 % of the
      total protein. The overall structure of this protein closely resembles soyabean
      beta-conglycinin, which accounts for 20 % of total soya protein (soya protein
      isolate; SPI). Many physiological beneficial effects of beta-conglycinin have
      been reported. GLUCODIATM is expected to produce beneficial effects with fewer
      intakes than SPI. We conducted two independent double-blind, placebo-controlled
      clinical studies. In the first (preliminary dose decision trial) study, mung bean
      protein was shown to exert physiological beneficial effects when 3.0 g were
      ingested per d. In the second (main clinical trial) study, mung bean protein
      isolate did not lower plasma glucose levels, although the mean insulin level
      decreased with consumption of mung bean protein. The homeostatic model assessment
      of insulin resistance (HOMA-IR) values significantly decreased with mung bean
      protein. The mean TAG level significantly decreased with consumption of mung bean
      protein isolate. A significant increase in serum adiponectin levels and
      improvement in liver function enzymes were observed. These findings suggest that
      GLUCODIATM could be useful in the prevention of insulin resistance and visceral
      fat accumulation, which are known to trigger the metabolic syndrome, and in the
      prevention of liver function decline.

PMID- 29372051
TI  - Effects of krill oil and lean and fatty fish on cardiovascular risk markers: a
      randomised controlled trial.
AB  - Fish consumption and supplementation with n-3 fatty acids reduce CVD risk. Krill
      oil is an alternative source of marine n-3 fatty acids and few studies have
      investigated its health effects. Thus, we compared krill oil supplementation with
      the intake of fish with similar amounts of n-3 fatty acids on different
      cardiovascular risk markers. In an 8-week randomised parallel study, thirty-six
      healthy subjects aged 18-70 years with fasting serum TAG between 1.3 and 4.0
      mmol/l were randomised to receive either fish, krill oil or control oil. In the
      fish group, subjects consumed lean and fatty fish, according to dietary
      guidelines. The krill and control group received eight capsules per d containing
      4 g oil per d. The weekly intake of marine n-3 fatty acids from fish given in the
      fish group and from krill oil in the krill group were 4103 and 4654 mg,
      respectively. Fasting serum TAG did not change between the groups. The level of
      total lipids (P = 0.007), phospholipids (P = 0.015), cholesterol (P = 0.009),
      cholesteryl esters (P = 0.022) and non-esterified cholesterol (P = 0.002) in the
      smallest VLDL subclass increased significantly in response to krill oil
      supplementation. Blood glucose decreased significantly (P = 0.024) in the krill
      group and vitamin D increased significantly in the fish group (P = 0.024).
      Furthermore, plasma levels of marine n-3 fatty acids increased significantly in
      the fish and krill groups compared with the control (all P <= 0.0003). In
      conclusion, supplementation with krill oil and intake of fish result in health
      beneficial effects. Although only krill oil reduced fasting glucose, fish provide
      health-beneficial nutrients, including vitamin D.

PMID- 29372053
TI  - Optimization of culture conditions for short-term maintenance, proliferation, and
      colony formation of porcine gonocytes.
AB  - Background: Gonocytes give rise to spermatogonial stem cells, and thereby play an
      essential role in establishing spermatogenesis. Optimized culture conditions for
      gonocytes provide an opportunity for their study and in vitro manipulation for
      potential application in reproductive technologies. Using six experiments in a
      step-wise design, we examined the effects of several culture conditions on the
      maintenance, proliferation, and colony formation of porcine gonocytes. Testis
      cells from neonatal piglets were cultured for 7 d in DMEM supplemented with 10%
      fetal bovine serum. The examined culture conditions included using different cell
      seeding densities, gonocyte proportions, incubation temperatures, sampling
      strategies, and medium changing regimens. Results: Confluency of cells was
      optimal (>90% by ~6 d) when 3.0 * 104 testis cells/cm2 containing ~40% gonocytes
      were used. Incubating the cells at 35  degrees C or 37  degrees C resulted in
      similar cell number and viability at confluency, but incubation at 35  degrees C
      resulted in a delayed confluency. In the first 2 d of culture, gonocytes remained
      mostly floating in the medium and gradually settled over the next 5 d.
      Consequently, not changing the medium for 7 d (as opposed to changing it every 2
      d) led to a significant increase in the number of gonocyte colonies by reducing
      the loss of "floating gonocytes". Conclusion: We found that gonocytes require the
      presence of a critical minimum number of somatic cells for settlement, and can
      proliferate and form growing colonies even in a basic medium. Large numbers of
      viable gonocytes remain floating in the medium for several days. The optimized
      culture conditions in the present study included seeding with 3.0 * 104 testis
      cells/cm2 containing ~40% gonocytes, incubating at 37  degrees C, and without
      changing the medium in the first week, which can result in improved colony
      formation of porcine gonocytes.

PMID- 29372055
TI  - HIV positive sero-status disclosure and its determinants among people living with
      HIV /AIDS following ART clinic in Jimma University Specialized Hospital,
      Southwest Ethiopia: a facility- based cross-sectional study.
AB  - Background: Even though, the disclosure of HIV sero- status to sexual partners,
      friends or relatives is the main tool for prevention and care strategies, most of
      the HIV/AIDS patients do not inform their close friends. The most common reasons
      for not disclosure of their status to the community were majorly fear of social
      rejection and discriminations. Therefore, this study assessed the HIV positive
      sero-status disclosure and its determinants among People Living with HIV /AIDS
      (PLWH/A) followed by the Antiretroviral therapy (ART) Clinic in Jimma University
      Specialized Hospital, Southwest Ethiopia. Methods: A facility based cross
      sectional study design was used among 351 ART patients that selected by
      systematic random sampling from ART clinic of Jimma University Specialized
      Hospital in March-2014. Data were collected through interviewer-administered
      questionnaires and analyzed using SPSS version 20.0 software. In a descriptive
      analysis frequency, mean and percentage were calculated. Bivariate and
      multivariate analyses were used to identify associated factors and the
      association between the explanatory and dependent variables was estimated.
      Results: Only 37.6% (n = 132) were revealed their HIV positive status to anyone.
      Disclosure was done towards the sexual partners (88.6%), close family (72.7%) and
      a larger population (18.2%). Age <= 39 years (AOR = 0.014 [95%, CI = 0.005,
      0.037]),Male sex (AOR = 3.039, [95% CI = 1.164, 7.935]), WHO stage III - IV at
      ART start(AOR = 2.766, [95%, CI = 1.321, 5.791]), presence of comorbidity (AOR =
      2.500, [95%, CI = 1.483, 4.214]), having any clinical symptoms for HIV(AOR =
      2.98, [95%, CI = 1.724, 5.152]),Low physical domain related quality of life (AOR
      = 3.83, [95%, CI = 2.008, 7.315]) and high social domain related quality of life
      (AOR = 0.053, [95%, CI = 0.022, 0.125]) were statistically significant
      association with their HIV sero-status disclosure. Conclusions: Findings of this
      study indicated, the disclosure of HIV status is very low. Discloser is more
      likely when the patient is older, male, and has a higher level of education.
      Clinical determinants for disclosure was the WHO stage III-IV, treatment duration
      of >=2 years, comorbidity, presence of clinical symptoms for HIV, low physical
      domain related quality of life, low social domain related quality of life and low
      overall quality of life.

PMID- 29372052
TI  - Nutritional requirements of meat-type and egg-type ducks: what do we know?
AB  - The demand for duck meat, duck eggs, and associated products is increasing each
      year. Classic and modern selection programs have been applied to enhance the
      economic traits of ducks to satisfy the requirements of consumers and enhance the
      incomes of producers. The nutritional requirements of unselected ducks may not be
      adequate, however, to fulfill the potential productivity performance of modern
      birds, including both meat-type and egg-type ducks. In particular, an imbalanced
      diet is associated with low productive performance and signs of nutritional
      deficiency (if insufficient nutrients are supplied), as well as with high feed
      costs and manure problems that reflect flock health and welfare (if excessive
      nutrients are supplied). Thus, the main aim of this review is to summarize the
      results of previous studies that estimated the nutrient requirements of meat-type
      and egg-type ducks in order to evaluate current knowledge and to identify further
      issues that need to be addressed. In addition, the results obtained in previous
      studies are compared in order to understand how to lower commercial feed costs,
      fulfill the genetic potential of selected ducks, protect the environment from
      pollution, and satisfy the welfare and health needs of ducks.

PMID- 29372054
TI  - Alfalfa-containing diets alter luminal microbiota structure and short chain fatty
      acid sensing in the caecal mucosa of pigs.
AB  - Background: Pork produced by outdoor-reared pigs raised mostly on alfalfa
      pastures attracts increasing population of consumer from most of the world. In
      China, pigs were raised with alfalfa-containing diets to seek for good quality
      pork. However, the influence of dietary alfalfa involving high level of insoluble
      dietary fiber (IDF) on pig intestinal luminal microbiota composition remains
      unclear. The objective of this study was to investigate the effects of alfalfa on
      luminal microbiota and short chain fatty acids (SCFA) production, and gene
      expressions involved in SCFA sensing, transporting and absorbing in pig caecal
      mucosa. Results: Twenty-four growing pigs were randomly allotted to four diets
      containing 0%, 5%, 10% and 15% alfalfa meal for a 28-d experiment. Ingestion of
      alfalfa meal-contained diets significantly increased the ratio of body weight
      gain to feed consumption. Illumina MiSeq sequencing of the V3 region of the 16S
      rRNA genes showed that alfalfa-containing diet significantly decreased the
      relative abundance of genera Turicibacter, Acidiphilium, Paracoccus,
      Propionibacterium, Corynebacterium, Pseudomonas, Acinetobacter, and
      Staphylococcus, and increased the relative abundance of genera Lachnospira,
      Marvinbryantia, and Desulfovibrio in the caecal digesta. Butyrate concentration
      was significantly increased in the hindgut by the supplementation of alfalfa meal
      in diets. The mRNA gene expressions of FFAR3, SMCT1, MCT1, PYY, and GCG were
      significantly increased in the caecal mucosa of pigs fed alfalfa meal.
      Conclusions: Our results suggested that alfalfa-containing diet has exerted
      significant impacts on caecal microbiota composition, butyrate concentration and
      significantly upregulated mRNA expression of host caecal mucosal genes involved
      in SCFA sensing and absorption as well as regulation of satiety.

PMID- 29372056
TI  - Home exercise improves the quality of sleep and daytime sleepiness of elderlies:
      a randomized controlled trial.
AB  - Background: Aging causes physiological changes which affect the quality of sleep.
      Supervised physical exercise is an important therapeutic resource to improve the
      sleep of the elderlies, however there is a low adherence to those type of
      programs, so it is necessary to implement an exercise program which is feasible
      and effective. The study aimed to test the hypothesis that a semi-supervised home
      exercise program, improves sleep quality and daytime sleepiness of elderlies of
      the community who present poor sleep quality. Methods: This was a randomized
      controlled trial study, conducted from May to September 2017, in Northeastern
      Brazil, with elderlies of the community aging 60 years old or older, sedentary,
      with lower scores or equal to 5 at the Pittsburgh Sleep Quality Index (PSQI) and
      without cognitive decline. From one hundred ninety-one potential participants
      twenty-eight refused to participate, therefore, one hundred thirty-one (mean age
      68 +/- 7 years), and 88% female, were randomly assigned to an intervention group 
      IG (home exercise and sleep hygiene, n = 65) and a control group - CG (sleep
      hygiene only, n = 66). Sleep assessment tools were used: PSQI, Epworth sleepiness
      scale (ESS) and clinical questionnaire of Berlin. The level of physical activity
      has been assessed by means of International Physical Activity Questionnaire
      adapted for the elderly (IPAQ) and Mini-Mental State Examination for cognitive
      decline. All participants were assessed before and after the 12-week intervention
      period and, also, the assessors were blind. Results: The IG showed significant
      improvement in quality of sleep with a mean reduction of 4.9 +/- 2.7 points in
      the overall PSQI (p < 0.01) and in all its 7 components of evaluation (p < 0.05),
      and improvement of secondary endpoint, daytime sleepiness, a decline of 2.8 +/-
      2.2 points in the ESS (p < 0.01). Conclusion: Our results suggest that semi
      supervised home exercise is effective in improving the quality of sleep and self
      referred daytime sleepiness of sedentary elderlies of the community who presented
      sleep disorders. Trial registration: Ensaiosclinicos.gov.br process number: RBR
      3cqzfy.

PMID- 29372057
TI  - Right orbital edema masquerading a hematologic malignancy.
AB  - Introduction: Multiple myeloma is caused by abnormal proliferation of plasma
      cells that affects more commonly African Americans. It classically presents with
      hypercalcemia, renal failure, anemia, and lytic bone lesions. The aim of this
      article is to present an unusual case of a 63-year-old African-American female
      with multiple myeloma who presented with worsening right-sided eye swelling for
      the past 3 weeks and to briefly review ophthalmologic manifestations of multiple
      myeloma. Case description: Our patient's presentation was associated with a
      throbbing frontal headache, nasal congestion, malaise, and weight loss.
      Differential diagnosis on admission included giant cell arteritis,
      conjunctivitis, preseptal cellulitis, glaucoma, acute sinusitis, or cavernous
      sinus thrombosis. Extensive ophthalmologic evaluation did not show any
      intraocular abnormality. However, a magnetic resonance imaging of the brain
      showed hyperintense foci in the right frontal calvarium leading to the eye
      swelling. Further evaluation revealed pancytopenia, elevated protein levels, and
      inverse albumin-globulin ratio suggestive of a plasma cell dyscrasia. A skeletal
      survey revealed multiple osteolytic lesions. Serum and urine protein
      electrophoresis revealed elevated immunoglobulin G Kappa monoclonal gammopathy.
      Bone marrow biopsy demonstrated a hypercellular marrow comprised at least 70%
      mature appearing plasma cells staining positive for CD138. Chemotherapy with
      cyclophosphamide, bortezomib, and dexamethasone was initiated. After 2 months of
      chemotherapy, orbital swelling has resolved with decrease in M-spike,
      immunoglobulin G, and serum kappa light chains. Conclusion: This case illustrates
      an unusual presentation of multiple myeloma which was eye swelling caused by bony
      infiltration in the calvarium. Although hematologic malignancies tend to have
      more specific signs and symptoms, they should be included in the differentials of
      unilateral orbital edema.

PMID- 29372058
TI  - The rewarding nature of provocation-focused rumination in women with borderline
      personality disorder: a preliminary fMRI investigation.
AB  - Background: Understanding why individuals with borderline personality disorder
      (BPD) ruminate on prior provocations, despite its negative outcomes, is crucial
      to improving interventions. Provocation-focused rumination may be rewarding in
      the short term by amplifying anger and producing feelings of justification,
      validation, and increased energy, while reducing self-directed negative affect.
      If provocation-focused rumination is utilized regularly as a rewarding emotion
      regulation strategy, it could result in increased activation in reward-related
      neural regions. The present pilot study examined neural correlates of provocation
      focused rumination, relative to other forms of thought, in BPD. Method:
      Functional magnetic resonance imaging (fMRI) was utilized to examine this theory
      in a pilot study of women diagnosed with BPD (n = 13) and healthy controls (n =
      16). All participants received highly critical feedback on a previously written
      essay in the scanner, followed by prompts to engage in provocation-focused, self
      focused, and neutral thought. Results: Whole-brain analyses showed that in
      response to the provocation, participants with BPD (compared to controls)
      demonstrated increased activation in the ventrolateral prefrontal cortex (PFC).
      BPD participants also showed greater activation in the dorsomedial PFC during
      provocation-focused rumination (relative to neutral-focus). Subsequent ROI
      analyses revealed that provocation-focused rumination (compared to neutral-focus)
      increased activation in the nucleus accumbens for the BPD group only.
      Conclusions: These findings, while preliminary due to the small sample size and
      limitations of the protocol, provide initial data consistent with the proposed
      neurobiological mechanism promoting provocation-focused rumination in BPD.
      Directions for further research are discussed.

PMID- 29372059
TI  - Factor V Leiden G1691A and prothrombin G20210A mutations among Palestinian
      patients with sickle cell disease.
AB  - Background: Vascular thrombosis is an important pathophysiological aspect of
      sickle cell disease (SCD). This study aimed to investigate the prevalence and
      clinical impact of factor V Leiden G1691A (FVL) and prothrombin G20210A mutations
      among Palestinian sickle cell disease (SCD) patients. Methods: A total of 117 SCD
      patients, including 59 patients with sickle cell anemia (SS), 33 patients with
      sickle beta-thalassemia and 25 individuals with sickle cell trait (AS) were
      studied. The control group consisted of 118 healthy individuals. FVL and
      prothrombin G20210A mutations were determined by RFLP PCR. Results: Analysis of
      the clinical history of SCD patients revealed that seven patients have had
      vascular complications such as ischemic stroke or deep vein thrombosis. In SCD
      patients, the inheritance of the FVL mutation showed a significantly higher
      incidence of pain in joints, chest and abdomen as well as regular dependence on
      blood transfusion compared to SCD with the wild type. Age- and sex-adjusted
      logistic regression analysis revealed a significant association between FVL and
      sickle cell anemia with an odds ratio (OR) of 5.6 (95% confidence intervals [CI]
      of 1.91-39.4, P = 0.039) in SS patients. However, increased prevalence of the FVL
      in AS subjects and sickle beta-thalassemia patients was not statistically
      significant compared to controls (OR 3.97, 95% CI 0.51-28.6, P = 0.17 and OR
      3.59, 95% CI 0.35-41.6, P = 0.26, respectively). The distribution of prothrombin
      G20210A mutation among SCD patients compared to controls was not significantly
      different, thus our findings do not support an association of this mutation with
      SCD. Conclusions: FVL was more prevalent among SS patients compared to controls
      and it was associated with higher incidence of disease complications among SCD
      patients.

PMID- 29372060
TI  - Pregnant mothers are more anemic than lactating mothers, a comparative cross
      sectional study, Bahir Dar, Ethiopia.
AB  - Background: Information on the hemoglobin status of pregnant and lactating
      mothers was scarce. The objectives of this study were to determine the burden and
      determinants of anemia in the pregnant and lactating mother. Methods: A
      comparative cross-sectional study was conducted. Descriptive statistics were used
      to identify the prevalence of anemia. Binary logistic regression and multiple
      linear regressions were used to identify the predictors of anemia. Results: The
      prevalence of anemia in lactating and pregnant women was 43.00% (95% CI
      {confidence interval}, 41% - 45%) and 84% of anemia was microcytic and hypocromic
      anemia. Anemia in lactating and pregnant women was positively associated with
      malaria infection [AOR{adjusted odds ratio} 3.61 (95% CI: 2.63-4.95)], abortion
      [AOR 6.63 (95% CI: 3.23-13.6)], hookworm infection [AOR 3.37 (95% CI: 2.33
      4.88)], tea consumption [AOR 3.63 (95% CI: 2.56-5.14)], pregnancy [AOR 2.24 (95%
      CI: 1.57-3.12)], and Mid-upper arm circumference [ B 0.36 (95% CI: 0.33, -0.4)].
      Anemia in pregnant and lactating mother was negatively associated with urban
      residence [AOR 0.68, (95% CI: 0.5-0.94)], iron supplementation during pregnancy
      [AOR 0.03 (95% CI, 0.02-0.04)], parity [ B -0.18 (95% CI: -0.23, -0.14)], age [B 
      0.03 (95% CI: -0.04, -0.03)]. Conclusion: The burden of anemia was higher in
      pregnant women than lactating women.

PMID- 29372061
TI  - Analysis of changes in trends in the consumption rates of benzodiazepines and
      benzodiazepine-related drugs.
AB  - Background: To analyse trends in the rates of consumption of benzodiazepine (BZD)
      anxiolytics, BZD hypnotics and non-BZD hypnotics and the association with
      contextual factors. Methods: Descriptive time series study. Units of analysis
      were monthly dose per inhabitant per day (DID) and dose per medical card per
      day(DCD) of benzodiazepine(BZD anxiolytics(BZD-A), BZD hypnotics(BZD-H) and non
      BZD hypnotics(Non-BZD-H) between January 2006-December 2015. We analysed 6
      primary healthcare districts(PHD) and used defined daily doses (DDDs) to
      calculate the monthly DIDs(overall and by ATC group). Trends and monthly
      percentage change (MPC) were analysed through joinpoint regression. Results: The
      annual DID increased by 26% overall, the trend was different across ATC groups.
      Consumption in BZD-A and BZD-H increased (27.1%,61.9%), consumption in Non-BZD-H
      decreased by 35%. There was high variability in DCD across the PHD, with an
      overall increase of 10.2%(5.7%-22.9%). By ATC, DCD increased by 10.4% in BZD
      A(4.2%-22.2%) and by 44.2% in BZD-H(33.2%-76.5%). The overall DCD in the Non-BZD
      H decreased by 42.1%(19.7%-50.8%). We found an initial upward trend in
      consumption of BZD-A until April/2008(monthly percentage change -MPC- +0.5%),
      followed by a slightly slower increase (+0.1%). No changes in trend were detected
      in BZD-H. In Non-BZD-H, we observed an upward trend until February/2013(+0.1%),
      followed by a sharp decrease until August/2013(-6.3%), and finally a slight
      decrease(-0.3%). Conclusions: BZD consumption has increased in the last decade,
      with variability across areas. The changes in trends do not coincide with the
      financial crisis, introduction of prescriptions by active ingredient, electronic
      prescriptions or copayment. The only decrease in the Non-BZD-H may be linked to
      an intervention.

PMID- 29372062
TI  - Inferior Olivary nucleus degeneration does not lessen tremor in essential tremor.
AB  - Background: In traditional models of essential tremor, the inferior olivary
      nucleus was posited to play a central role as the pacemaker for the tremor.
      However, recent data call this disease model into question. Case presentation:
      Our patient had progressive, long-standing, familial essential tremor. Upper limb
      tremor began at age 10 and worsened over time. It continued to worsen during the
      nine-year period he was enrolled in our brain donation program (age 85 - 94
      years), during which time the tremor moved from the moderate to severe range on
      examination. On postmortem examination at age 94, there were degenerative changes
      in the cerebellar cortex, as have been described in the essential tremor
      literature. Additionally, there was marked degeneration of the inferior olivary
      nucleus, which was presumed to be of more recent onset. Such degeneration has not
      been previously described in essential tremor postmortems. Despite the presence
      of this degeneration, the patient's tremor not only persisted but it continued to
      worsen during the final decade of his life. Conclusions: Although the
      pathophysiology of essential tremor is not completely understood, evidence such
      as this suggests that the inferior olivary nucleus does not play a critical role
      in the generation of tremor in these patients.

PMID- 29372063
TI  - Production of Aspergillus niger biomass on sugarcane distillery wastewater:
      physiological aspects and potential for biodiesel production.
AB  - Background: Sugarcane distillery waste water (SDW) or vinasse is the residual
      liquid waste generated during sugarcane molasses fermentation and alcohol
      distillation. Worldwide, this effluent is responsible for serious environmental
      issues. In Reunion Island, between 100 and 200 thousand tons of SDW are produced
      each year by the three local distilleries. In this study, the potential of
      Aspergillus niger to reduce the pollution load of SDW and to produce interesting
      metabolites has been investigated. Results: The fungal biomass yield was 35 g L-1
      corresponding to a yield of 0.47 g of biomass/g of vinasse without nutrient
      complementation. Analysis of sugar consumption indicated that mono-carbohydrates
      were initially released from residual polysaccharides and then gradually consumed
      until complete exhaustion. The high biomass yield likely arises from
      polysaccharides that are hydrolysed prior to be assimilated as monosaccharides
      and from organic acids and other complex compounds that provided additional C
      sources for growth. Comparison of the size exclusion chromatography profiles of
      raw and pre-treated vinasse confirmed the conversion of humic- and/or phenolic
      like molecules into protein-like metabolites. As a consequence, chemical oxygen
      demand of vinasse decreased by 53%. Interestingly, analysis of intracellular
      lipids of the biomass revealed high content in oleic acid and physical properties
      relevant for biodiesel application. Conclusions: The soft-rot fungus A. niger
      demonstrated a great ability to grow on vinasse and to degrade this complex and
      hostile medium. The high biomass production is accompanied by a utilization of
      carbon sources like residual carbohydrates, organic acids and more complex
      molecules such as melanoidins. We also showed that intracellular lipids from
      fungal biomass can efficiently be exploited into biodiesel.

PMID- 29372065
TI  - As in Real Estate, Location Is What Matters: A Case Report of Transplant Ureteral
      Obstruction Due to an Inguinal Hernia.
AB  - Background: Kidney allograft dysfunction is common and often reversible but can
      lead to allograft loss if not promptly evaluated. Transplant ureteral obstruction
      in an inguinal hernia is a rare cause of allograft dysfunction, but early
      recognition may prevent allograft loss. Case Presentation: We present a case of a
      man with acute kidney allograft dysfunction who received a deceased donor kidney
      transplant 6 years earlier for end-stage kidney disease secondary to polycystic
      kidney disease. Abdominal ultrasounds revealed hydronephrosis without full
      visualization of the transplant ureter. Abdominal computed tomography revealed
      moderate hydronephrosis of the transplant kidney due to obstructed herniation of
      the transplant ureter in a right inguinal hernia. A stent was inserted into the
      transplant ureter to prevent further allograft dysfunction and facilitate hernia
      repair. Conclusions: Transplant ureteral obstruction is a rare cause of acute
      kidney allograft dysfunction, and its detection can be challenging. The
      recognition of transplant ureteral obstruction is vital to timely management for
      preventing allograft loss.

PMID- 29372064
TI  - Canadians Seeking Solutions and Innovations to Overcome Chronic Kidney Disease
      (Can-SOLVE CKD): Form and Function.
AB  - Purpose of review: This article serves to describe the Can-SOLVE CKD network, a
      program of research projects and infrastructure that has excited patients and
      given them hope that we can truly transform the care they receive. Issue: Chronic
      kidney disease (CKD) is a complex disorder that affects more than 4 million
      Canadians and costs the Canadian health care system more than $40 billion per
      year. The evidence base for guiding care in CKD is small, and even in areas where
      evidence exists, uptake of evidence into clinical practice has been slow.
      Compounding these complexities are the variations in outcomes for patients with
      CKD and difficulties predicting who is most likely to develop complications over
      time. Clearly these gaps in our knowledge and understanding of CKD need to be
      filled, but the current state of CKD research is not where it needs to be. A
      culture of clinical trials and inquiry into the disease is lacking, and much of
      the existing evidence base addresses the concerns of the researchers but not
      necessarily those of the patients. Program overview: The Canadian Institutes of
      Health Research (CIHR) has launched the national Strategy for Patient-Oriented
      Research (SPOR), a coalition of federal, provincial, and territorial partners
      dedicated to integrating research into care. Canadians Seeking Solutions and
      Innovations to Overcome Chronic Kidney Disease (Can-SOLVE CKD) is one of five pan
      Canadian chronic kidney disease networks supported through the SPOR. The vision
      of Can-SOLVE CKD is that by 2020 every Canadian with or at high risk for CKD will
      receive the best recommended care, experience optimal outcomes, and have the
      opportunity to participate in studies with novel therapies, regardless of age,
      sex, gender, location, or ethnicity. Program objective: The overarching objective
      of Can-SOLVE CKD is to accelerate the translation of knowledge about CKD into
      clinical research and practice. By focusing on the patient's voice and
      implementing relevant findings in real time, Can-SOLVE CKD will transform the
      care that CKD patients receive, and will improve kidney health for future
      generations.

PMID- 29372067
TI  - The relationship between physical inactivity and mental wellbeing: Findings from
      a gamification-based community-wide physical activity intervention.
AB  - Mental ill health accounts for 13 per cent of total global disease burden with
      predictions that depression alone will be the leading cause of disease burden
      globally by 2030. Poor mental health is consistently associated with deprivation,
      low income, unemployment, poor education, poorer physical health and increased
      health-risk behaviour. A plethora of research has examined the relationship
      between physical activity and mental wellbeing; however, the influence of
      community-wide gamification-based physical activity interventions on mental
      wellbeing, to the authors' knowledge, is yet to be explored. In view of this
      paucity of attention, the current study examined the relationship between
      physical activity and mental wellbeing pre/post a community-wide, gamification
      based intervention. The findings revealed that increases in mental wellbeing were
      significantly greater for the least active prior to the intervention, and a
      strong, positive correlation between increase in physical activity and increase
      in mental wellbeing was observed.

PMID- 29372066
TI  - Self-regulation resources and physical activity participation among adults with
      type 2 diabetes.
AB  - Physical activity plays a crucial role in the prevention and treatment of type 2
      diabetes. Therefore, it is important to understand why so few adults with type 2
      diabetes regularly engage in physical activity. The role of self-regulation in
      the context of health-related behavior adherence, especially in terms of physical
      activity engagement and adherence, has largely been reviewed based on the
      strength energy model. Building on this line of research, the aim of this
      theoretical work was to highlight how self-regulation and ego depletion can
      influence the lower rate of physical activity participation among adults with
      type 2 diabetes, compared to adults from the general population.

PMID- 29372068
TI  - Congenital absence of the portal vein in a cat.
AB  - Case summary: A 9-month-old female neutered domestic shorthair cat presented with
      a history of episodic ptyalism, lethargy and abnormal behaviour. The clinical
      signs together with elevated pre- and post-prandial bile acid concentrations were
      consistent with hepatic encephalopathy (HE). In the absence of a portosystemic
      shunt (PSS) on abdominal ultrasound, medical management of HE was established
      with a protein-restricted diet and lactulose and the neurological signs resolved.
      Following an episode of acute vomiting and haemorrhagic diarrhoea at 19 months of
      age abdominal ultrasonography was repeated. The portal vein could not be
      demonstrated ultrasonographically; instead, portal vein tributaries were tortuous
      and communicated with the caudal vena cava (CdVC) at the level of the left
      kidney. CT angiography (CTA) confirmed the absence of the portal vein. CTA
      demonstrated the tortuous terminations of the portal tributaries, and several
      systemic veins, draining into the CdVC via a large-diameter paracaval vessel at
      the level of the left kidney. Gastrointestinal signs were stabilised and medical
      management for HE of a protein-restricted diet and lactulose was re-established.
      Relevance and novel information: Congenital absence of the portal vein has not
      been described previously in the cat and should be considered in cats presenting
      with signs suggestive of a PSS and HE. The portal vein in the cat can be
      demonstrated using ultrasound, but complex congenital vascular malformations of
      the portal or systemic abdominal veins should be characterised using CTA and
      further distinguished from other vascular anomalies that may present with similar
      ultrasonographic features.

PMID- 29372069
TI  - Diagnosis and treatment of latent tuberculosis in patients with multiple
      sclerosis, expert consensus. On behalf of the Colombian Association of Neurology,
      Committee of Multiple Sclerosis.
AB  - Background: Multiple sclerosis is an inflammatory and neurodegenerative
      demyelinating disease. Current treatment of multiple sclerosis focuses on the use
      of immunomodulatory, immunosuppressant, and selective immunosuppressant agents.
      Some of these medications may result in high risk of opportunistic infections
      including tuberculosis. Objective: The purpose of this study was to obtain
      consensus from a panel of neurologists, pulmonologists, infectious disease
      specialists, and epidemiology experts regarding the diagnosis, treatment, and
      monitoring of latent tuberculosis in patients with multiple sclerosis. Methods: A
      panel of experts in multiple sclerosis and tuberculosis was established. The
      methodological process was performed in three phases: definition of questions,
      answer using Delphi methodology, and the discussion of questions not agreed.
      Results: Tuberculosis screening is suggested when multiple sclerosis drugs are
      prescribed. The recommended tests for latent tuberculosis are tuberculin and
      interferon gamma release test. When an anti-tuberculosis treatment is indicated,
      monitoring should be performed to determine liver enzyme values with
      consideration of age as well as comorbid conditions such as a history of
      alcoholism, age, obesity, concomitant hepatotoxic drugs, and history of liver
      disease. Conclusion: Latent tuberculosis should be considered in patients with
      multiple sclerosis who are going to be treated with immunomodulatory and
      immunosuppressant medications. Transaminase level monitoring is required on a
      periodic basis depending on clinical and laboratory characteristics. In addition
      to the liver impairment, other side effects should be considered when Isoniazid
      is prescribed.

PMID- 29372070
TI  - A feasibility study of a randomised controlled trial to examine the impact of the
      ABCDE bundle on quality of life in ICU survivors.
AB  - Background: Early rehabilitation has been found to prevent delirium and weakness
      that can hamper the recovery of intensive care unit (ICU) survivors. Integrated
      clinical practice guidelines for managing patient pain, agitation and delirium
      (PAD) have been developed. The Awakening and Breathing Coordination, Delirium
      monitoring/management, and Early exercise/mobility (ABCDE) bundle provides a
      strategy to implement PAD guidelines into everyday clinical practice. However,
      there is limited evidence on the effectiveness of the ABCDE bundle in the
      literature.The purpose of this study was to evaluate the feasibility of
      conducting a full-scale randomised controlled trial comparing the ABCDE bundle to
      standard care in an ICU. Trial feasibility was defined as the successful
      recruitment and retention of trial participants, adherence to the intervention,
      identification of barriers to the intervention, and the rigorous collection of
      outcome data. Methods: A prospective, single-centre, randomised controlled
      feasibility study was conducted. Thirty adult mechanically ventilated
      participants were recruited from an eight-bed ICU in south east Queensland,
      Australia, between April 2015 and December 2015. Participants were randomised to
      receive either the ABCDE bundle or standard routine management. The ABCDE bundle
      integrated prescribed awakening and breathing trials, delirium monitoring and
      management, and prescribed exercise and mobility regimes. Feasibility outcomes
      measured included recruitment and retention rates, intervention fidelity, and the
      feasibility of participant outcome data collection. Outcome measurement assessors
      were blinded to participant assignment. It was not possible to blind the research
      team or the participant to group assignment. Results: In total, 30 (81.1%) of 37
      eligible participants consented and were randomised to the intervention group (n
      = 15) or the control group (n = 15). Of these, 23 (76.6%) participants
      successfully completed the 90-day post discharge assessment. A lengthy
      recruitment period of 8 months was related to overly stringent inclusion and
      exclusion criteria. Intervention adherence exceeded defined success rates with
      participation in awakening and breathing trials, delirium monitoring and exercise
      interventions performed on 80.2, 97.4 and 90.2% of ventilated days respectively.
      Outcome assessments were successfully and accurately performed at ICU and
      hospital discharge and 90-day post hospital discharge. Intervention participants
      were deemed to be delirious on 39.6% of mechanically ventilated days indicating a
      requirement for a scripted regime to prevent delirium. Conclusions: With minor
      adjustment of inclusion and exclusion criteria, the inclusion of delirium
      management protocols, and encouragement of family engagement and involvement, a
      large-scale definitive randomised controlled trial to test the impact of the
      ABCDEF bundle will be feasible. Trial registration: Australian New Zealand
      Clinical Trials Registry 12614000763640 Date registered 17/08/2014.

PMID- 29372071
TI  - A randomised feasibility study to investigate the impact of education and the
      addition of prompts on the sedentary behaviour of office workers.
AB  - Background: Office workers have been identified as being at risk of accumulating
      high amounts of sedentary time in prolonged events during work hours, which has
      been associated with increased risk of a number of long-term health
      conditions.There is some evidence that providing advice to stand at regular
      intervals during the working day, and using computer-based prompts, can reduce
      sedentary behaviour in office workers. However, evidence of effectiveness,
      feasibility and acceptability for these types of intervention is currently
      limited. Methods: A 2-arm, parallel group, cluster-randomised feasibility trial
      to assess the acceptability of prompts to break up sedentary behaviour was
      conducted with office workers in a commercial bank (n = 21). Participants were
      assigned to an education only group (EG) or prompt and education group (PG). Both
      groups received education on reducing and breaking up sitting at work, and the PG
      also received hourly prompts, delivered by Microsoft Outlook over 10 weeks,
      reminding them to stand. Objective measurements of sedentary behaviour were made
      using activPAL monitors worn at three time points: baseline, in the last 2 weeks
      of the intervention period and 12 weeks after the intervention. Focus groups were
      conducted to explore the acceptability of the intervention and the motivations
      and barriers to changing sedentary behaviour. Results: Randomly generated,
      customised prompts, delivered by Microsoft Outlook, with messages about breaking
      up sitting, proved to be a feasible and acceptable way of delivering prompts to
      office workers. Participants in both groups reduced their sitting, but changes
      were not maintained at follow-up. The education session seemed to increase
      outcome expectations of the benefits of changing sedentary behaviour and promote
      self-regulation of behaviour in some participants. However, low self-efficacy and
      a desire to conform to cultural norms were barriers to changing behaviour.
      Conclusions: Prompts delivered by Microsoft Outlook were a feasible, low-cost way
      of prompting office workers to break up their sedentary behaviour, although
      further research is needed to determine whether this has an additional impact on
      sedentary behaviour, to education alone. The role of cultural norms, and
      promoting self-efficacy, should be considered in the design of future
      interventions. Trial registration: This study was registered retrospectively as a
      clinical trial on ClinicalTrials.gov (ID no. NCT02609282) on 23 March 2015.

PMID- 29372072
TI  - The market trend analysis and prospects of cancer molecular diagnostics kits.
AB  - Background: The molecular diagnostics market can be broadly divided into PCR (rt
      PCR, d-PCR), NGS(Next Generation Sequencing), Microarray, FISH(Fluorescent in
      situ-hybridization) and other categories, based on the diagnostic technique.
      Also, depending on the disease being diagnosed, the market can also be divided
      into cancer, infectious diseases, HIV/STDs (herpes, syphilis), and women's health
      issues such as breast cancer, cervical cancer, ovarian cancer, HPV(human
      papillomavirus), and vaginitis.Chromosome analysis (including Fluorescent In-situ
      Hybridization) is one type of blood cancer diagnostic method, which involves the
      direct detection of individual cells with chromosomal translocation, but there
      have been problems of sensitivity when using this method. PCR targeting
      individual genes or the RT (reverse transcription)-PCR method offers outstanding
      sensitivity, but one drawback is the risk of false-positive reaction caused by
      contamination of samples, etc. Blood cancer molecular diagnostics kits allow us
      to overcome these shortcomings, and related products have been under development,
      with a focus on improving detection sensitivity, enabling multiple tests, and
      reducing the cost and diagnostic time. Results: Blood cancer molecular
      diagnostics is usually performed based on platforms such as PCR. The global
      market for blood cancer molecular diagnostics kits is $ 335.9 million as of 2016
      and is expected to reach $ 6980 million in 2026 with an average annual growth
      rate of 32.9%. The market in South Korea is anticipated to grow at an average
      annual rate of 28.9%, from $ 3.75 million as of 2016 to $ 60.89 million in 2026.
      Conclusions: The Market for blood cancer molecular diagnostics kits is judged to
      be higher in growth possibility due to the increase in the number of cancer
      patients.

PMID- 29372074
TI  - Jules Gonin and the Nobel Prize: pioneer of retinal detachment surgery who almost
      received a Nobel Prize in medicine.

PMID- 29372073
TI  - Flight feather development: its early specialization during embryogenesis.
AB  - Background: Flight feathers, a type of feather that is unique to extant/extinct
      birds and some non-avian dinosaurs, are the most evolutionally advanced type of
      feather. In general, feather types are formed in the second or later generation
      of feathers at the first and following molting, and the first molting begins at
      around two weeks post hatching in chicken. However, it has been stated in some
      previous reports that the first molting from the natal down feathers to the
      flight feathers is much earlier than that for other feather types, suggesting
      that flight feather formation starts as an embryonic event. The aim of this study
      was to determine the inception of flight feather morphogenesis and to identify
      embryological processes specific to flight feathers in contrast to those of down
      feathers. Results: We found that the second generation of feather that shows a
      flight feather-type arrangement has already started developing by chick embryonic
      day 18, deep in the skin of the flight feather-forming region. This was confirmed
      by shh gene expression that shows barb pattern, and the expression pattern
      revealed that the second generation of feather development in the flight feather
      forming region seems to start by embryonic day 14. The first stage at which we
      detected a specific morphology of the feather bud in the flight feather-forming
      region was embryonic day 11, when internal invagination of the feather bud
      starts, while the external morphology of the feather bud is radial down-type.
      Conclusion: The morphogenesis for the flight feather, the most advanced type of
      feather, has been drastically modified from the beginning of feather
      morphogenesis, suggesting that early modification of the embryonic morphogenetic
      process may have played a crucial role in the morphological evolution of this key
      innovation. Co-optation of molecular cues for axial morphogenesis in limb
      skeletal development may be able to modify morphogenesis of the feather bud,
      giving rise to flight feather-specific morphogenesis of traits.

PMID- 29372075
TI  - Feasibility of using experimental high viscosity silicone oils: a pilot study.
AB  - Background: Polydimethyl silicones (silicone oils) are used in complex retinal
      surgeries, including difficult or recurrent retinal detachments, severe eye
      trauma, and other indications for long term tamponade. Two major problems with
      currently available silicone oils are emulsification and recurrent retinal
      detachment. The primary endpoint of this study was to evaluate the toxicity and
      safety of high viscosity silicone oils and second, the feasibility of using them
      with currently available vitrectomy systems. Methods: In this experimental study,
      8 eyes of 8 New Zealand White rabbits underwent vitrectomy. The vitreous cavities
      of 2 eyes were filled with medical grade 5500 cS silicone oil, 4 eyes with 12,500
      cS oil, and 2 eyes with 30,000 cS oil for 3 months, after which the animals were
      sacrificed and the eyes sent for histopathological examination. The duration
      required to inject 5 cc each of 1300, 12,500 and 30,000 cS oils, using a
      commercially available system (Alcon VFC Pac) were also evaluated. Results:
      Retinal histopathology was comparable in all eyes, with no excess toxic effect or
      damage seen in eyes with experimental oils. All oils were readily injectable with
      the VFC Pac system. Conclusions: High viscosity experimental silicone oils have
      similar chemical and physical properties to lower viscosity oils currently used.
      Therefore, toxicities are expected to be similar. In a small pilot sample of 8
      rabbit eyes filled with silicone oil for 3 months, histopathology in eyes with
      12,500, 30,000 cS or medical grade 5500 cS silicone oil were similar. Injecting
      these oils using available vitrectomy equipment is feasible. New, high viscosity
      silicone oils may offer several advantages over currently available oils for some
      patients.

PMID- 29372077
TI  - The Role of Patients' Families in Cancer Treatment Decision-Making: Perspectives
      among Eastern and Western families.

PMID- 29372076
TI  - Effects of diffusion time on non-Gaussian diffusion and intravoxel incoherent
      motion (IVIM) MRI parameters in breast cancer and hepatocellular carcinoma
      xenograft models.
AB  - Background: Perfusion-related intravoxel incoherent motion (IVIM) and non
      Gaussian diffusion magnetic resonance (MR) parameters are becoming important
      biomarkers for differentiating malignant from benign tumors without contrast
      agents. However, diffusion-time dependence has rarely been investigated in
      tumors. Purpose: To investigate the relationship between diffusion time and
      diffusion parameters in breast cancer and hepatocellular carcinoma xenograft
      mouse models. Material and Methods: Diffusion-weighted MR images (DWI) were
      obtained on a 7-T magnetic resonance imaging (MRI) scanner at two different
      diffusion times (9.6 ms and 27.6 ms) in human breast cancer (MDA-MB-231) and
      hepatocellular carcinoma (HepG2 and PLC/PRF/5) xenograft mouse models. Perfusion
      related IVIM (fIVIM and D*) and non-Gaussian diffusion (ADC0 and K) parameters
      were estimated. Parametric maps of diffusion changes with the diffusion times
      were generated using a synthetic apparent diffusion coefficient (sADC) obtained
      from b = 438 and 2584 s/mm2. Results: ADC0 values significantly decreased when
      diffusion times were changed from 9.6 ms to 27.6 ms in MDA-MB-231, HepG2, and
      PLC/PRF/5 groups (P = 0.0163, 0.0351, and 0.0170, respectively). K values
      significantly increased in MDA-MB-231 and HepG2 groups (P < 0.0003 and = 0.0007,
      respectively); however, no significant difference was detected in the PLC/PRF/5
      group. fIVIM values increased, although not significantly (P = 0.164-0.748). The
      maps of sADC changes showed that diffusion changes with the diffusion time were
      not homogeneous across tumor tissues. Conclusion: Diffusion MR parameters in both
      breast cancer and HCC xenograft models were found to be diffusion time-dependent.
      Our results show that diffusion time is an important parameter to consider when
      interpreting DWI data.

PMID- 29372078
TI  - Trauma Care in Oman: Where do we stand and where should we be heading?

PMID- 29372079
TI  - Deciphering the Role of the Barr Body in Malignancy: An insight into head and
      neck cancer.
AB  - X chromosome inactivation is the epitome of epigenetic regulation and long non
      coding ribonucleic acid function. The differentiation status of cells has been
      ascribed to X chromosome activity, with two active X chromosomes generally only
      observed in undifferentiated or poorly differentiated cells. Recently, several
      studies have indicated that the reactivation of an inactive X chromosome or X
      chromosome multiplication correlates with the development of malignancy; however,
      this concept is still controversial. This review sought to shed light on the role
      of the X chromosome in cancer development. In particular, there is a need for
      further exploration of the expression patterns of X-linked genes in cancer cells,
      especially those in head and neck squamous cell carcinoma (HNSCC), in order to
      identify different prognostic subpopulations with distinct clinical implications.
      This article proposes a functional relationship between the loss of the Barr body
      and the disproportional expression of X-linked genes in HNSCC development.

PMID- 29372080
TI  - Troponin Testing in the Emergency Department: Real world experience.
AB  - Objectives: The aim of this study was to examine patterns of troponin testing in
      the emergency department of a large tertiary care hospital in Oman and to
      determine its effect on patient management, including length of hospital stay
      (LOS). Methods: This retrospective study analysed the medical records of all
      adult patients undergoing troponin testing in the emergency department of the
      Sultan Qaboos University Hospital, Muscat, Oman, during the month of July 2015.
      Patients who presented with an ST-elevation myocardial infarction were excluded.
      Results: A total of 4,845 patients attended the emergency department during the
      study period; of these, troponin tests were ordered for 588 patients. The
      majority of the patients had negative troponin test results (81.3%). Chest pain,
      palpitations and breathlessness were the most common presenting complaints for
      those with positive troponin results. However, 41.8% of patients did not have any
      cardiac symptoms. Individuals with positive troponin tests had a significantly
      longer LOS compared to those with negative tests (mean: three versus one day; P =
      0.001). In total, only 28.2% of those with positive troponin test results had
      final diagnoses associated with a cardiac condition, such as heart failure, an
      acute coronary syndrome (ACS), atrial fibrillation or other types of arrhythmia.
      Conclusion: A positive troponin test was associated with increased LOS; however,
      only a small proportion of these patients had a final diagnosis associated with a
      cardiac condition. Guidelines should be provided to ensure that troponin testing
      is performed only in cases where an ACS is suspected.

PMID- 29372081
TI  - Epidemiology of Chronic Hepatitis C Infections at a Tertiary Care Centre in Oman.
AB  - Objectives: Chronic hepatitis C (CHC) is a leading cause of liver cirrhosis and
      hepatocellular carcinoma (HCC) worldwide. However, there is a lack of data
      regarding the epidemiology of CHC in Oman. This study aimed to describe the
      clinicopathological characteristics and outcomes of CHC-infected patients at a
      tertiary care hospital in Oman. Methods: This retrospective descriptive hospital
      based study included all CHC-infected patients who presented to the Sultan Qaboos
      University Hospital (SQUH) in Muscat, Oman, between January 2010 and December
      2015. The baseline demographic, clinical, laboratory and radiological data of the
      patients were analysed. Results: A total of 603 CHC-infected patients were
      identified during the study period; of these, 65.8% were male and the mean age
      was 44.8 +/- 16.5 years. The main risk factors associated with CHC infection were
      intravenous drug abuse (23.9%) and a history of blood transfusions (20.7%). The
      most prevalent virus genotypes were 1 and 3 (44.0% and 35.1%, respectively). Upon
      initial presentation, 33.0% of the cohort had liver cirrhosis; of these, 48.7%
      had decompensated cirrhosis and 23.1% had HCCs. Liver transplantation was only
      performed for 7.5% of the cirrhosis patients, mostly as a curative treatment for
      HCC. Conclusion: The implementation of national policies to prevent hepatitis C
      transmission and encourage the early screening of at-risk patients is recommended
      to reduce the burden and consequences of this disease in Oman.

PMID- 29372082
TI  - Interpreting Neonatal Growth Parameters in Oman: Are we doing it right?
AB  - Objectives: This study aimed to compare reference anthropometric measures of
      Omani neonates with the international standard growth charts of the World Health
      Organization (WHO) in order to determine the appropriateness of these growth
      charts to assess the growth of Omani neonates. Methods: This cross-sectional
      study included all healthy full-term Omani neonates born between November 2014
      and November 2015 at the Sultan Qaboos University Hospital, Muscat, Oman. Birth
      weight, length and head circumference measurements were identified and compared
      to those of the 2006 WHO growth charts. Results: A total of 2,766 full-term
      neonates were included in the study, of which 1,401 (50.7%) were male and 1,365
      (49.3%) were female. Mean birth weights for Omani males and females were 3.16 +/-
      0.39 kg and 3.06 +/- 0.38 kg, respectively; these were significantly lower than
      the WHO standard measurements (P <0.001). Similarly, the mean head circumferences
      of Omani males and females (33.8 +/- 1.27 cm and 33.3 +/- 1.26 cm, respectively)
      were significantly lower than those reported in the WHO growth charts (P <0.001).
      In contrast, mean lengths for Omani males and females (52.0 +/- 2.62 cm and 51.4
      +/- 2.64 cm, respectively) were significantly higher than the WHO standard
      measurements (P <0.001). Conclusion: The WHO growth charts might not be
      appropriate for use with Omani neonates; possible alternatives should therefore
      be considered, such as national growth charts based on local data.

PMID- 29372083
TI  - Discrepancies Between Planned and Actual Operating Room Turnaround Times at a
      Large Rural Hospital in Germany.
AB  - Objectives: While several factors have been shown to influence operating room
      (OR) turnaround times, few comparisons of planned and actual OR turnaround times
      have been performed. This study aimed to compare planned and actual OR turnaround
      times at a large rural hospital in Northern Germany. Methods: This retrospective
      study examined the OR turnaround data of 875 elective surgery cases scheduled at
      the Marienhospital, Vechta, Germany, between July and October 2014. The frequency
      distributions of planned and actual OR turnaround times were compared and
      correlations between turnaround times and various factors were established,
      including the time of day of the procedure, patient age and the planned duration
      of the surgery. Results: There was a significant difference between mean planned
      and actual OR turnaround times (0.32 versus 0.64 hours; P <0.001). In addition,
      significant correlations were noted between actual OR turnaround times and the
      time of day of the surgery, patient age, actual duration of the procedure and
      staffing changes affecting the surgeon or the medical specialty of the surgery (P
      <0.001 each). The quotient of actual/planned OR turnaround times ranged from
      1.733-3.000. Conclusion: Significant discrepancies between planned and actual OR
      turnaround times were noted during the study period. Such findings may be
      potentially used in future studies to establish a tool to improve OR planning,
      measure OR management performance and enable benchmarking.

PMID- 29372084
TI  - Mortality Rate and Years of Life Lost Due to Prostate Cancer in Yazd Province,
      Iran: A 10-year study.
AB  - Objectives: Prostate cancer is a leading cause of cancer-related deaths. The
      number of deaths and years of life lost (YLL) due to a disease can be used to
      monitor health status, assess healthcare needs and determine the prioritisation
      and allocation of health resources within a population; in addition, the latter
      calculation can serve as a baseline indicator of premature mortality. This study
      aimed to measure prostate cancer-related mortality and YLL in Yazd Province,
      Iran. Methods: This study included all prostate cancer-related deaths in Yazd
      Province reported between March 2001 and March 2010. Mortality data were obtained
      from a provincial death registration system which integrates data from different
      sources. YLL was calculated based on an individual's age at death and their life
      expectancy according to age group. Results: During the study period, prostate
      cancer was the fourth most common fatal cancer among men, resulting in 324 deaths
      or 10.0% of all cancer-related deaths. The crude mortality rate per 100,000
      individuals increased from 4.7 in 2001 to 8.8 in 2010. Premature deaths caused
      1,358.7 YLL and the YLL caused by prostate cancer deaths more than doubled from
      94.7 in 2001 to 196.5 in 2010. Conclusion: Due to changes in population
      structure, it is likely that the burden of prostate cancer will continue to
      increase in Yazd Province. As such, it is necessary that the national health
      system implements screening programmes and improves public awareness of prostate
      cancer-associated risk factors.

PMID- 29372085
TI  - Distribution of Trauma Care Facilities in Oman in Relation to High-Incidence Road
      Traffic Injury Sites: Pilot study.
AB  - Objectives: Road traffic injuries (RTIs) are considered a major public health
      problem worldwide. In Oman, high numbers of RTIs and RTI-related deaths are
      frequently registered. This study aimed to evaluate the distribution of trauma
      care facilities in Oman with regards to their proximity to RTI-prevalent areas.
      Methods: This descriptive pilot study analysed RTI data recorded in the national
      Royal Oman Police registry from January to December 2014. The distribution of
      trauma care facilities was analysed by calculating distances between areas of
      peak RTI incidence and the closest trauma centre using Google Earth and Google
      Maps software (Google Inc., Googleplex, Mountain View, California, USA). Results:
      A total of 32 trauma care facilities were identified. Four facilities (12.5%)
      were categorised as class V trauma centres. Of the facilities in Muscat, 42.9%
      were ranked as class IV or V. There were no class IV or V facilities in Musandam,
      Al-Wusta or Al-Buraimi. General surgery, orthopaedic surgery and neurosurgery
      services were available in 68.8%, 59.3% and 12.5% of the centres, respectively.
      Emergency services were available in 75.0% of the facilities. Intensive care
      units were available in 11 facilities, with four located in Muscat. The mean
      distance between a RTI hotspot and the nearest trauma care facility was 34.7 km;
      however, the mean distance to the nearest class IV or V facility was 83.3 km.
      Conclusion: The distribution and quality of trauma care facilities in Oman needs
      modification. It is recommended that certain centres upgrade their levels of
      trauma care in order to reduce RTI-associated morbidity and mortality in Oman.

PMID- 29372086
TI  - Evaluation of Family Planning Counselling in North Jordan.
AB  - Objectives: Counselling plays a key role in enhancing reproductive services,
      providing contraception-related information and supporting long-term family
      planning for women of childbearing age. This study aimed to evaluate family
      planning counselling sessions in selected governmental and private clinics in
      northern Jordan. Methods: This cross-sectional study was conducted between
      January and June 2016 in Irbid, Jordan. A total of 200 women attending two
      private clinics affiliated with the Jordanian Association for Family Planning and
      Protection (JAFPP) and six governmental clinics were invited to participate in
      the study. Counselling sessions were attended by an independent observer and
      evaluated with regards to their compliance with the standard Greet, Ask, Tell,
      Help, Explain, Return (GATHER) framework. Results: A total of 198 women
      participated in the study (response rate: 99.0%), including 80 women (40.4%) from
      JAFPP clinics and 118 (59.6%) from governmental clinics. In total, 42.9% of the
      counselling sessions were deemed adequate, with providers applying 80% or more of
      the GATHER framework, while 26.8% of the sessions were deemed semi-adequate and
      30.3% were considered inadequate. Counselling services provided in the
      governmental clinics were significantly less adequate than those provided in
      JAFPP clinics (P <0.001). Conclusion: The quality of counselling services in
      governmental family planning centres in Jordan needs to be improved to ensure
      that women receive the highest possible level of care. Healthcare policymakers
      should therefore focus on developing and supporting effective family planning
      counselling services in northern Jordan.

PMID- 29372087
TI  - Diabetes-Related Knowledge and Preventative Practices Among Government Employees
      with Diabetes in Kuwait.
AB  - Objectives: Diabetes mellitus (DM)-related knowledge and preventative practices
      are vital for the successful management of this condition. In Kuwait, few studies
      have been conducted to evaluate the knowledge and preventative practices of DM
      patients. This study aimed to assess DM-related knowledge and preventative
      practices among government employees with DM in Kuwait and to examine
      associations between DM knowledge, preventative practices and other variables.
      Methods: This cross-sectional study was conducted in June 2015 and involved 345
      employees with DM from 15 government ministries in Kuwait. A self-administered
      Arabic-language questionnaire was designed to assess DM-related knowledge and
      preventative practices based on the Diabetes Knowledge Test and the
      recommendations of the American Diabetes Association, respectively. Results: A
      total of 312 ministry employees agreed to participate in the study (response
      rate: 90.4%). The mean age was 45.6 +/- 10.6 years. A total of 63.4% were male
      and 64.1% were Kuwaiti. The median DM knowledge score was 9 out of 14 and the
      median preventative practice score was 5 out of 14. High knowledge scores were
      significantly associated with education (beta = 1.510; P <=0.001) and income
      (beta = 0.896; P <=0.001). High preventative practice scores were significantly
      associated with income (beta = 1.376; P = 0.002), DM duration (beta = 0.919; P =
      0.026) and knowledge scores (beta = 1.783; P = 0.015). Conclusion: Government
      employees in Kuwait were found to have average DM knowledge and poor preventative
      practices. It is therefore imperative that policy-makers develop educational and
      health-promoting campaigns to target government employees with DM in Kuwait.

PMID- 29372088
TI  - Soft Tissue Rosai-Dorfman Disease: Case report.
AB  - Rosai-Dorfman disease (RDD) is a rare benign proliferative histiocytic disorder
      characterised by massive lymphadenopathy. While extranodal involvement can occur
      in generalised RDD, isolated soft tissue RDD (STRDD) is extremely rare. We report
      a 17-year-old male patient who presented to the maxillofacial outpatient
      department of the Sultan Qaboos Hospital, Salalah, Oman, in 2015 with a painless
      cheek mass which had been slowly growing over the previous two months. Routine
      histopathological examinations and immunohistochemistry confirmed a diagnosis of
      STRDD. Currently, surgical excision is considered to be the most effective
      curative treatment for STRDD, as the outcomes of other treatment modalities are
      still unknown. Despite its rarity, STRDD should be considered in the differential
      diagnosis of histiocytic soft tissue lesions.

PMID- 29372089
TI  - A Case of Persistent Urogenital Sinus: Pitfalls and challenges in diagnosis.
AB  - Persistent urogenital sinus (PUGS) is a rare anomaly whereby the urinary and
      genital tracts fail to separate during embryonic development. We report a three
      year-old female child who was referred to the Sabah Women & Children Hospital,
      Sabah, Malaysia, in 2016 with a pelvic mass. She had been born prematurely at 36
      gestational weeks via spontaneous vaginal delivery in 2013 and initially
      misdiagnosed with neurogenic bladder dysfunction. The external genitalia appeared
      normal and an initial sonogram and repeat micturating cystourethrograms did not
      indicate any urogenital anomalies. She therefore underwent clean intermittent
      catheterisation. Three years later, the diagnosis was corrected following the
      investigation of a persistent cystic mass posterior to the bladder. At this time,
      a clinical examination of the perineum showed a single opening into the
      introitus. Magnetic resonance imaging of the pelvis revealed gross hydrocolpos
      and a genitogram confirmed a diagnosis of PUGS, for which the patient underwent
      surgical separation of the urinary and genital tracts.

PMID- 29372090
TI  - Thyrotoxic Neuropathy: A rare cause of acute flaccid paraplegia.
AB  - Acute polyneuropathy is a rare manifestation of severe hyperthyroidism. We report
      a 22-year-old Omani male who presented to the Sohar Hospital, Sohar, Oman, in
      2016 with acute-onset rapidly progressive flaccid areflexic paraplegia as the
      presenting manifestation of thyrotoxicosis. Nerve conduction studies revealed
      mixed axonal and demyelinating polyneuropathy in both the motor and sensory
      nerves. Treatment of the hyperthyroidism with beta-blockers and carbimazole along
      with physiotherapy resulted in the patient's full recovery and the alleviation of
      his symptoms. Besides highlighting this rare association, this report underscores
      the importance of including thyroid function tests in the evaluation of patients
      with acute polyneuropathy.

PMID- 29372091
TI  - Pitting Oedema in a Patient with Lumbar Disc Herniation: Case report of an
      unusual association.
AB  - Oedema refers to the excessive accumulation of fluid within intercellular tissues
      as a result of disequilibrium between the capillary hydrostatic and oncotic
      pressure gradients. Lumbar disc herniation (LDH) commonly causes lower back pain
      and radicular leg pain. We report a 57-year-old female who presented to the
      neurosurgery clinic of the Bam University of Medical Sciences, Bam, Iran, in 2015
      with pain and pitting oedema in the bilateral lower extremities. Magnetic
      resonance imaging confirmed a diagnosis of LDH of the L3-L4 and L4-L5 vertebrae.
      The patient subsequently underwent a bilateral laminotomy and foraminotomy of the
      involved vertebrae to relieve her pain. Following the surgery, there was a
      complete resolution of the LDH-related symptoms as well as the oedema. Although
      LDH has never before been associated with oedema, it may nevertheless cause lower
      limb oedema in exceptional and rare cases, as highlighted in this patient.

PMID- 29372092
TI  - Intravenous Remifentanil Analgaesia for an Obstetric Patient with Type I
      Neurofibromatosis and a Factor V Leiden Mutation.
AB  - Type I neurofibromatosis is characterised by altered skin pigmentation and the
      growth of benign tumours, particularly along the peripheral nerves and central
      nervous system. We report a 36-year-old primigravida woman in labour who was
      admitted to the obstetric suite of the Hospital Sant Joan de Deu, Barcelona,
      Spain, in 2007 with hypothyroidism, type I neurofibromatosis and a factor V
      Leiden mutation. Due to a lack of cranial and spinal imaging data, an epidural
      was not indicated; instead, continuous intravenous remifentanil analgaesia was
      administered. The remifentanil infusion was self-titrated by the patient using a
      visual analogue scale, with the dosage ranging from 0.01 to 0.25 MUg/kg/minute.
      Due to rotational dystocia, Kjelland-type forceps were used during the delivery.
      After birth, the infant was found to have Apgar scores of 9 and 10, with no
      maternal or neonatal adverse effects observed. Although still controversial,
      remifentanil may be a successful alternative for analgaesia in similar cases;
      however, the specific risks and benefits for each patient should be considered
      prior to administration.

PMID- 29372093
TI  - Gingival Leiomyosarcoma in a Young Woman: Case report and literature review.
AB  - Leiomyosarcoma (LMS) is a rare mesenchymal malignancy, of which 3-10% of cases
      occur in the head and neck region. We report a 22-year-old woman who was referred
      to the University Hospital of Siena, Italy, in 2016 with an ostensibly benign
      asymptomatic lump on the mandibular gingiva. The lesion grew rapidly, causing
      otalgia in the right ear. An excisional biopsy was performed and primary LMS was
      diagnosed histologically. Subsequently, the patient underwent radical re-excision
      of the perilesional mucosa, a partial bone resection and the extraction of four
      teeth. No recurrences or metastases were detectable at a 20-month follow-up. This
      report discusses the differential diagnosis of LMS with regards to other benign
      and malignant lesions and reviews the recent literature on primary and secondary
      oral LMS. Due to its innocuous clinical features-including its asymptomatic
      nature and presentation at a young age-this aggressive malignancy can go
      undetected; therefore, an early histopathological diagnosis is crucial.

PMID- 29372094
TI  - Broad Ligament Lipoleiomyoma Masses: Two curious cases masquerading as ovarian
      carcinomas.
AB  - Lipoleiomyomas are an extremely rare form of uterine leiomyoma; moreover, the
      occurrence of this type of tumour on the broad ligament is even rarer. We report
      two cases of broad ligament lipoleiomyomas in 15- and 38-year-old female patients
      who presented to the Lok Nayak Jai Prakash Hospital in New Delhi, India, between
      2016 and 2017. In both cases, the preoperative diagnosis was of a solid ovarian
      malignancy. Most broad ligament tumours are mistaken for ovarian masses as they
      are difficult to diagnose radiologically.

PMID- 29372095
TI  - Cardiovocal Syndrome: A rare cause of hoarseness in a patient with a history of
      pulmonary tuberculosis.
AB  - Hoarseness is a common clinical condition with underlying causes which can vary
      from reversible and benign to life-threatening and malignant. Cardiovocal
      syndrome may cause hoarseness secondary to left recurrent laryngeal nerve palsy
      when the recurrent laryngeal nerve is mechanically affected due to enlarged
      cardiovascular structures. We report a 28-year-old male who presented to the
      Government Medical College, Thiruvananthapuram, India, in 2013 with hoarseness.
      He had undergone irregular treatment for pulmonary tuberculosis (TB) two years
      previously. Fiber-optic laryngoscopy indicated left vocal cord palsy and a
      computed tomography scan of the chest revealed features of pulmonary hypertension
      with extensive enlargement of the pulmonary arteries. An echocardiogram confirmed
      severe pulmonary arterial hypertension with severe tricuspid regurgitation. He
      was diagnosed with left recurrent laryngeal palsy secondary to cardiovocal
      syndrome. Although reports exist of recurrent laryngeal palsy in TB, this case
      appears to be the first to report cardiovocal syndrome in a patient treated for
      pulmonary TB.

PMID- 29372096
TI  - Calvarial Tuberculosis in a Preschool-Aged Child: An uncommon entity.
AB  - Calvarial tuberculosis is a rare manifestation of tuberculosis, especially in
      children under five years of age. We report a two-and-a-half-year-old male child
      who presented to the Nilratan Sircar Medical College, Kolkata, India, in 2015
      with frontoparietal fluctuant swelling of three months' duration. He had also had
      chronic sinus discharge from the left lower eyelid over the previous six months.
      Computed tomography of the head revealed a frontal swelling along with erosion of
      both the outer and inner plates of the left frontal bone. Fine needle aspiration
      of the pus indicated the presence of acid-fast bacilli. Unfortunately, no primary
      focus of tuberculosis could be established. The patient improved after one year
      of antitubercular therapy without requiring any surgical intervention and with no
      sign of subsequent disease recurrence.

PMID- 29372097
TI  - Paget's Disease of the Breast: A dangerous imitator of eczema.

PMID- 29372098
TI  - T Cell Large Granular Lymphocyte Leukaemia with Cutaneous Infiltration.

PMID- 29372099
TI  - A race to uncover a panoramic view of primary liver cancer.

PMID- 29372100
TI  - The ascent of immune checkpoint inhibitors: is the understudy ready for a leading
      role?

PMID- 29372101
TI  - Cell cycle regulation and anticancer drug discovery.
AB  - Cellular growth, development, and differentiation are tightly controlled by a
      conserved biological mechanism: the cell cycle. This cycle is primarily regulated
      by cyclin-dependent kinase (CDK)-cyclin complexes, checkpoint kinases, and CDK
      inhibitors. Deregulation of the cell cycle is a hallmark of the transformation of
      normal cells into tumor cells. Given its importance in tumorigenesis, several
      cell cycle inhibitors have emerged as potential therapeutic drugs for the
      treatment of cancers-both as single-agent therapy and in combination with
      traditional cytotoxic or molecular targeting agents. In this review, we discuss
      the mechanisms underlying cell cycle regulation and present small-molecule
      anticancer drugs that are under development, including both pan-CDK inhibitors
      and CDK4/6-selective inhibitors. In addition, we provide an outline of some
      promising CDK inhibitors currently in preclinical and clinical trials that target
      cell cycle abnormalities in various cancers.

PMID- 29372102
TI  - Camptothecin-based nanodrug delivery systems.
AB  - The drug camptothecin has a wide range of antitumor effects in cancers including
      gastric cancer, rectal and colon cancer, liver cancer, and lung cancer.
      Camptothecin-based drugs inhibit topoisomerase 1 (Topo 1), leading to destruction
      of DNA, and are currently being used as important chemotherapeutic agents in
      clinical antitumor treatment. However, the main obstacle associated with cancer
      therapy is represented by systemic toxicity of conventional anticancer drugs and
      their low accumulation at the tumor site. In addition, low bioavailability, poor
      water solubility, and other shortcomings hinder their anticancer activity.
      Different from traditional pharmaceutical preparations, nanotechnology-dependent
      nanopharmaceutical preparations have become one of the main strategies for
      different countries worldwide to overcome drug development problems. In this
      review, we summarized the current hotspots and discussed a variety of
      camptothecin-based nanodrugs for cancer therapy. We hope that through this
      review, more efficient drug delivery systems could be designed with potential
      applications in clinical cancer therapy.

PMID- 29372103
TI  - Brain metastasis in advanced colorectal cancer: results from the South Australian
      metastatic colorectal cancer (SAmCRC) registry.
AB  - Objective: Brain metastasis is considered rare in metastatic colorectal cancer
      (mCRC); thus, surveillance imaging does not routinely include the brain. The
      reported incidence of brain metastases ranges from 0.6% to 3.2%. Methods: The
      South Australian mCRC Registry (SAmCRC) was analyzed to assess the number of
      patients presenting with brain metastasis during their lifetime. Due to small
      numbers, a descriptive analysis is presented. Results: Only 59 patients of 4,100
      on the registry at the time of analysis had developed brain metastasis (1.4%).
      The clinical characteristics of those with brain metastasis were as follows: the
      median age was 65.3 years and 51% were female. Where the V-Ki-ras2 Kirsten rat
      sarcoma viral oncogene homolog (KRAS) mutation status of the tumor was known, the
      majority harbored a KRAS mutation (55%); 31 (53%) underwent craniotomy and 55
      (93%) underwent whole-brain radiotherapy. The median survival time from diagnosis
      of brain metastasis was 4.2 months (95% confidence interval 2.9-5.5). Patients
      who underwent craniotomy and radiotherapy had superior survival compared to those
      who underwent whole-brain radiotherapy (8.5 months vs. 2.2 months, respectively).
      Data from the SAmCRC (a population-based registry) confirm that brain metastases
      are rare and the median time to development is approximately 2 years.
      Conclusions: Brain metastasis is a rare outcome in advanced CRC. Patients within
      the registry tended to be female, young in age, and harbored with higher rates of
      KRAS mutations. Whether routine surveillance brain scanning should be considered
      remains controversial given the relative rarity of developing brain metastases in
      mCRC and ultimately, most patients with central nervous system involvement die
      from their extracranial disease.

PMID- 29372104
TI  - Promoter methylation of Wnt/beta-Catenin signal inhibitor TMEM88 is associated
      with unfavorable prognosis of non-small cell lung cancer.
AB  - Objective: Recent research has indicated that altered promoter methylation of
      oncogenes and tumor suppressor genes is an important mechanism in lung cancer
      development and progression. In this study, we investigated the association
      between promoter methylation of TMEM88, a possible inhibitor of the Wnt/beta
      Catenin signaling, and the survival of patients with non-small cell lung cancer
      (NSCLC). Methods: Twelve pairs of tumor and adjacent non-tumor samples were used
      for microarray analyses of DNA methylation and gene expression. For validation,
      more than two hundred additional samples were analyzed for methylation using
      bisulfite pyrosequencing and for gene expression using qRT-PCR. Then the cell
      function were tested by wound healing, transwell, CCK8 and cell cycle assay.
      Results: Our analysis of patient specimens showed that TMEM88 methylation was
      higher in NSCLC tumors (82.2% +/- 10.3, P < 0.01) compared with the adjacent
      normal tissues (65.9% +/- 7.2). The survival analysis revealed that patients with
      high TMEM88 methylation had a shorter overall survival (46 months) compared with
      patients with low TMEM88 methylation (>56 months;P=0.021). In addition, we found
      that demethylation treatment could inhibit tumor cell proliferation, migration,
      and invasion, which was supportive of an association between methylation and
      survival. Conclusions: Based on these consistent observations, we concluded that
      TMEM88 may play an important role in NSCLC progression and that promoter
      methylation of TMEM88 may serve as a biomarker for NSCLC prognosis and treatment.

PMID- 29372106
TI  - Thermogenic protein UCP1 and UCP3 expression in non-small cell lung cancer:
      relation with glycolysis and anaerobic metabolism.
AB  - Uncoupling protein 1 (UCP1) is a proton transporter/channel residing on the inner
      mitochondrial membrane and is involved in cellular heat production. Using
      immunohistochemistry, we investigated the expression of UCP1 and UCP3 in a series
      of 98 patients with non-small cell lung cancer (NSCLC) treated with surgery.
      Expression patterns were correlated with histopathological variables, prognosis,
      and the expression of enzymes/proteins related to cell metabolism. Bronchial
      epithelium did not express UCP1 or UCP3, while alveolar cells strongly expressed
      UCP1. In tumors, strong expression of UCP1 and UCP3 was recorded in 43/98 (43.8%)
      and 27/98 (27.6%) cases, respectively. UCP1 was significantly associated with
      squamous cell histology (P = 0.05), whilst UCP3 was more frequently overexpressed
      in large cell carcinomas (P = 0.08), and was inversely related to necrosis (P =
      0.009). In linear regression analysis, UCP1 was directly related to markers of
      glycolysis [hexokinase (HXKII) and phosphofructokinase (PFK1)] and anaerobic
      glucose metabolism [pyruvate dehydrogenase kinase (PDK1) and lactate
      dehydrogenase (LDH5)]. UCP3 was directly linked with a glucose transporter
      (GLUT2), monocarboxylate transporter (MCT2), glycolysis markers (PFK1 and
      aldolase), and with the phosphorylation of pyruvate dehydrogenase (pPDH). Kaplan
      Meier survival analysis showed that UCP3 was significantly related to poor
      prognosis in squamous cell carcinomas (P = 0.04). UCP1 and UCP3 are overexpressed
      in a large subgroup of non-small cell lung tumors and their expression coincides
      with increased glucose absorption, intensified glycolysis, and anaerobic glucose
      usage. Whether UCPs are targets for therapeutic interventions in lung cancer is a
      hypothesis that demands further investigation.

PMID- 29372105
TI  - Profile of the breast cancer susceptibility marker rs4245739 identifies a role
      for miRNAs.
AB  - Objective: To determine the influence of the single nucleotide polymorphism (SNP)
      rs4245739 on the binding and expression of microRNAs and subsequent MDM4
      expression and the correlation of these factors with clinical determinants of ER
      negative breast cancers. Methods: FindTar and miRanda were used to detect the
      manner in which potential microRNAs are affected by the SNP rs4245739-flanking
      sequence. RNA sequencing data for ER-negative breast cancer from The Cancer
      Genome Atlas (TCGA) were used to compare the expression of miR-184, miR-191, miR
      193a, miR-378, and MDM4 in different rs4245739 genotypes. Results: Comparison of
      ER-negative cancer patients with and without the expression of miR-191 as well as
      profile microRNAs (miR-184, miR-191, miR-193a and miR-378 altogether) can
      differentiate the expression of MDM4 among different rs4245739 genotypes.
      Although simple genotyping alone did not reveal significant clinical
      relationships, the combination of genotyping and microRNA profiles was able to
      significantly differentiate individuals with larger tumor size and lower number
      of involved lymph nodes (P < 0.05) in the risk group (A allele). Conclusions: We
      present two novel methods to analyze SNPs within 3'UTRs that use: (i) a single
      miRNA marker expression and (ii) an expression profile of miRNAs predicted to
      bind to the SNP region. We demonstrate that the application of these two methods,
      in particular the miRNA profile approach, permits detection of new molecular and
      clinical features related to the rs4245739 variant in ER-negative breast cancer.

PMID- 29372107
TI  - Increased expression of YAP1 in prostate cancer correlates with extraprostatic
      extension.
AB  - Objective: Yes associated protein 1 (YAP1) is a member of the Hippo pathway,
      acting as a transcriptional coactivator. To elucidate the role of YAP1 and
      phosphorylated (p)YAP1 in prostate cancer (PCa) tumorigenesis, we investigated
      their expression in clinical samples of PCa and cell lines. Methods: Fifty-four
      tumor, adjacent nontumor, and prostate intraepithelial neoplasia (PIN) tissues
      from patients with PCa after radical prostatectomy were selected from a
      retrospective cohort and studied using immunohistochemistry (IHC). Protein and
      mRNA expression levels of YAP1 were evaluated by Western blot analysis and
      quantitative real-time reverse transcription PCR, respectively, in cancer cell
      lines. Publicly available gene expression datasets were downloaded to analyze
      YAP1 mRNA and protein levels in PCa tissue samples. Results: IHC analysis of PCa
      tissues revealed that YAP1 staining intensities were moderate to weak in the
      nucleus and cytoplasm of tumor cells, whereas adjacent normal epithelia showed
      strong staining. We observed that benign prostates were characterized by higher
      expression levels of both nuclear (P=0.004) and cytosolic (P=0.005) YAP1. pYAP1
      staining was weak in the cytoplasm and absent in the nucleus of all the tissues
      investigated. YAP1 expression was an indicator of extraprostatic extension (EPE).
      The level of YAP1 was negatively correlated with the level of the androgen
      receptor (AR) in The Cancer Genome Atlas dataset and Western blot analysis of
      cell lines. Conclusions: Our study suggested that YAP1 expression is
      heterogeneous in PCa tissue samples; therefore, YAP1 might play different roles
      in different aspects of PCa progression. This might involve AR-YAP1 interplay in
      PCa.

PMID- 29372108
TI  - Complete pathologic response after chemoradiotherapy in a patient with rectal
      squamous cell carcinoma: a case report.
AB  - Squamous cell carcinoma (SCC) of the rectum is a rare disease. A 59-year-old man
      presented with SCC of the middle rectum located 10 cm from the anus. The stage of
      the tumor was revealed to be T3N+M0. The patient received a combined treatment
      with cisplatin and fluorouracil in concomitance with external radiation therapy.
      He then underwent an anterior resection of the rectum. The postoperative
      histopathological findings classified the tumor as ypT0N0 with cancer-free
      margins and lymph nodes. Treatment of SCC remains very challenging, and the
      acquisition of more consistent data is needed.

PMID- 29372109
TI  - Brain metastasis in non-small cell lung cancer (NSCLC) patients with uncommon
      EGFR mutations: a report of seven cases and literature review.
AB  - Brain metastasis (BM) arising from non-small cell lung cancer (NSCLC) with rare
      epidermal growth factor receptor (EGFR) mutations is quite rare. The prognosis
      and therapeutic effects of BM remain enigmatic. To the best of our knowledge,
      this is the first report to make a separate analysis of BM from NSCLC patients
      with original uncommon EGFR mutations. We retrospectively reviewed 7 cases of BM
      arising from 42 cases of uncommon EGFR mutated lung cancer in Tianjin Medical
      University Cancer Institute and Hospital. We also performed a literature review
      to assess therapeutic features and outcomes.

PMID- 29372110
TI  - The accuracy of a non-invasive glucose monitoring device does not depend on
      clinical characteristics of people with type 2 diabetes mellitus.
AB  - Objective: GlucoTrack is a non-invasive device that indirectly measures glucose
      fluctuation in the earlobe tissue. Thus, its accuracy may be subjected to a time
      lag between glucose concentration in blood and tissue. This time lag was shown to
      depend on individual characteristics related to microvascular complications, such
      as diabetes duration, HbA1c level, and smoking history. Therefore, the current
      study investigated the effects of these factors on GlucoTrack performance.
      Research design and methods: Clinical trials were conducted on 114 people with
      type 2 diabetes. Device performance was clinically evaluated using Clarke error
      grid (CEG) analysis and numerically evaluated using the distribution of absolute
      relative difference (ARD) values. Results: CEG analysis revealed that 98.0% of
      glucose readings were within the clinically acceptable CEG A + B zones. Total
      mean ARD was 22.7%. Clinical and numerical accuracies were comparable between
      never smokers and former/current smokers, but slightly reduced in the HbA1c >=
      7.5% group and in the diabetes duration >=15 years group. Yet, likelihood ratio
      and parametric bootstrap tests statistically demonstrated that ARD values did not
      depend on diabetes duration, HbA1c level, or smoking history. Conclusions:
      GlucoTrack performance does not depend on diabetes duration, HbA1c level, and
      smoking history, indicating the device is suitable for various people with type 2
      diabetes.

PMID- 29372111
TI  - Positively worded subscale score of the Perceived Stress Scale is associated with
      cognitive domain function.
AB  - Objectives: To examine the cross-sectional associations of the separate subscales
      of the Perceived Stress Scale (PSS) and tests measuring cognitive domains in
      older adults. Methods: 897 adults over the age of 70 free of amnestic mild
      cognitive impairment and dementia and enrolled in the Einstein Aging Study made
      up the study sample. The PSS-14 was used to measure stress. Three cognitive
      domains (language, episodic memory, and frontal-executive) had previously been
      found using principle component analysis. Linear regression analyses were used to
      determine the relationship between the PSS subscales and cognitive domain
      function. Results: The study sample had a mean age of 79.1 years and 62.8% were
      female. Bivariate correlations show that the PSS-14 positively worded subscale of
      the PSS (PSS-PW) was significantly associated with all three cognitive domains
      (language: r = -0.15, p < 0.001; episodic memory: r = -0.16, p < 0.001; frontal
      executive: r = -0.21, p <0.001) while the negatively worded subscale of the PSS
      (PSS-NW) was not significantly associated with any cognitive domain. In linear
      regression analyses adjusted for age, white race, gender, years of education, and
      depressive symptoms, the PSS-PW remained significantly associated with each of
      the cognitive domains. The PSS-NW was not associated with any cognitive domains
      in any model. The PSS-14 was significantly associated with language and episodic
      memory, but not the frontal-executive domain. Conclusion: Worse PSS-PW scores are
      associated with reduced cognitive function in the executive, memory, and language
      domains in nondemented older adults. The PSS-PW subscale correlated better with
      cognitive function than the overall PSS-14. Future research should evaluate the
      temporality of the association and if stress reduction therapies improve
      cognitive performance.

PMID- 29372112
TI  - Objective Assessment of Activity Limitation in Glaucoma with Smartphone Virtual
      Reality Goggles: A Pilot Study.
AB  - Purpose: To evaluate the use of smartphone-based virtual reality to objectively
      assess activity limitation in glaucoma. Methods: Cross-sectional study of 93
      patients (54 mild, 22 moderate, 17 severe glaucoma). Sociodemographics, visual
      parameters, Glaucoma Activity Limitation-9 and Visual Function Questionnaire -
      Utility Index (VFQ-UI) were collected. Mean age was 67.4 +/- 13.2 years; 52.7%
      were male; 65.6% were driving. A smartphone placed inside virtual reality goggles
      was used to administer the Virtual Reality Glaucoma Visual Function Test (VR
      GVFT) to participants, consisting of three parts: stationary, moving ball,
      driving. Rasch analysis and classical validity tests were conducted to assess
      performance of VR-GVFT. Results: Twenty-four of 28 stationary test items showed
      acceptable fit to the Rasch model (person separation 3.02, targeting 0). Eleven
      of 12 moving ball test items showed acceptable fit (person separation 3.05,
      targeting 0). No driving test items showed acceptable fit. Stationary test person
      scores showed good criterion validity, differentiating between glaucoma severity
      groups (P = 0.014); modest convergence validity, with mild to moderate
      correlation with VFQ-UI, better eye (BE) mean deviation, BE pattern deviation, BE
      central scotoma, worse eye (WE) visual acuity, and contrast sensitivity (CS) in
      both eyes (R = 0.243-0.381); and suboptimal divergent validity. Multivariate
      analysis showed that lower WE CS (P = 0.044) and greater age (P = 0.009) were
      associated with worse stationary test person scores. Conclusions: Smartphone
      based virtual reality may be a portable objective simulation test of activity
      limitation related to glaucomatous visual loss. Translational Relevance: The use
      of simulated virtual environments could help better understand the activity
      limitations that affect patients with glaucoma.

PMID- 29372113
TI  - Preperimetric Glaucoma Prospective Study (PPGPS): Predicting Visual Field
      Progression With Basal Optic Nerve Head Blood Flow in Normotensive PPG Eyes.
AB  - Purpose: To investigate the site specificity of visual field changes in eyes with
      normotensive preperimetric glaucoma (PPG), and to determine factors influencing
      visual field progression. Methods: This prospective study comprised 84 eyes of 84
      normotensive PPG patients followed for at least 16 months. Optic nerve head (ONH)
      blood flow was assessed with tissue-area mean blur rate (MBRT), derived from
      laser speckle flowgraphy. Total deviation (TD) was measured in each sector of the
      Garway-Heath map to evaluate the site specificity of visual field loss. Subjects
      with a TD slope in the first quartile were classified as progressive, and other
      subjects as nonprogressive. Linear and multiple regression analyses were
      performed to determine factors affecting visual field progression. Results: TD in
      the superior sector significantly decreased in the subjects overall during the
      follow-up periods (-0.48 +/- 1.92 dB/y, P = 0.025). Linear regression analysis
      showed that basal MBRT-inferior was correlated significantly with TD-superior
      slope (r = 0.332, P = 0.002). Furthermore, basal MBRT was significantly lower in
      this sector in the progressive than the nonprogressive group (P = 0.010).
      Multiple linear regression analysis revealed that basal MBRT-inferior was the
      only predictive factor for TD-superior slope (beta = 0.329, P = 0.005).
      Conclusions: These findings suggest that superior-sector visual field progression
      is most common in normotensive PPG eyes, and that reduced basal ONH blood flow is
      associated with visual field progression. Translational Relevance: These findings
      provide new insight into the involvement of ONH blood flow impairment in glaucoma
      pathogenesis, and demonstrate the importance of assessing ONH blood flow to
      determine visual field progression in normotensive PPG.

PMID- 29372114
TI  - The Effect of Topical Substance-P Plus Insulin-like Growth Factor-1 (IGF-1) on
      Epithelial Healing After Photorefractive Keratectomy in Rabbits.
AB  - Purpose: To determine whether topical Substance-P (SP) plus insulin-like growth
      factor-1 (IGF-1) can improve corneal healing after photorefractive surface
      ablation in a rabbit. Methods: After a 9.0-mm corneal de-epithelialization using
      a combination of chemical (18% alcohol) and mechanical debridement, excimer
      photorefractive surface ablation was performed bilaterally in eight rabbits (16
      eyes) with an 8.0-mm ablation zone and 70-MUm depth. The right eye was treated
      with SP (250 MUg/mL) and IGF-1 (25 ng/mL) in hyaluronic acid, one drop twice a
      day, and the other eye treated with only hyaluronic acid. The epithelial healing
      process was documented photographically twice a day until healing was complete.
      Six rabbits were sacrificed 6 weeks after photorefractive keratectomy (PRK) and
      corneas examined histologically. Results: Seven of eight rabbit eyes treated with
      SP/IGF-1 healed in a shorter time than the untreated eye. For rabbit #6, both
      eyes healed at the same time. The average healing time (total time until wound
      closure) for the treated eyes was 99 hours, while the average healing time for
      the untreated eyes was 170 hours (P = 0.0490). A persistent epithelial defect was
      found in two of the nontreated eyes but none in the treated eyes. Corneal
      pathology showed some degree of epithelial separation in the central corneal
      wound in three out of six nontreated eyes and in just the treated eye of rabbit
      #6. Conclusion: Topical SP plus IGF-1 increases the epithelial healing rate after
      PRK. There may have been beneficial effects upon cell adhesion as well.
      Translational Relevance: Better and faster healing.

PMID- 29372115
TI  - Benchmark datasets for phylogenomic pipeline validation, applications for
      foodborne pathogen surveillance.
AB  - Background: As next generation sequence technology has advanced, there have been
      parallel advances in genome-scale analysis programs for determining evolutionary
      relationships as proxies for epidemiological relationship in public health. Most
      new programs skip traditional steps of ortholog determination and multi-gene
      alignment, instead identifying variants across a set of genomes, then summarizing
      results in a matrix of single-nucleotide polymorphisms or alleles for standard
      phylogenetic analysis. However, public health authorities need to document the
      performance of these methods with appropriate and comprehensive datasets so they
      can be validated for specific purposes, e.g., outbreak surveillance. Here we
      propose a set of benchmark datasets to be used for comparison and validation of
      phylogenomic pipelines. Methods: We identified four well-documented foodborne
      pathogen events in which the epidemiology was concordant with routine
      phylogenomic analyses (reference-based SNP and wgMLST approaches). These are
      ideal benchmark datasets, as the trees, WGS data, and epidemiological data for
      each are all in agreement. We have placed these sequence data, sample metadata,
      and "known" phylogenetic trees in publicly-accessible databases and developed a
      standard descriptive spreadsheet format describing each dataset. To facilitate
      easy downloading of these benchmarks, we developed an automated script that uses
      the standard descriptive spreadsheet format. Results: Our "outbreak" benchmark
      datasets represent the four major foodborne bacterial pathogens (Listeria
      monocytogenes, Salmonella enterica, Escherichia coli, and Campylobacter jejuni)
      and one simulated dataset where the "known tree" can be accurately called the
      "true tree". The downloading script and associated table files are available on
      GitHub: https://github.com/WGS-standards-and-analysis/datasets. Discussion: These
      five benchmark datasets will help standardize comparison of current and future
      phylogenomic pipelines, and facilitate important cross-institutional
      collaborations. Our work is part of a global effort to provide collaborative
      infrastructure for sequence data and analytic tools-we welcome additional
      benchmark datasets in our recommended format, and, if relevant, we will add these
      on our GitHub site. Together, these datasets, dataset format, and the underlying
      GitHub infrastructure present a recommended path for worldwide standardization of
      phylogenomic pipelines.

PMID- 29372116
TI  - FUSTr: a tool to find gene families under selection in transcriptomes.
AB  - Background: The recent proliferation of large amounts of biodiversity
      transcriptomic data has resulted in an ever-expanding need for scalable and user
      friendly tools capable of answering large scale molecular evolution questions.
      FUSTr identifies gene families involved in the process of adaptation. This is a
      tool that finds genes in transcriptomic datasets under strong positive selection
      that automatically detects isoform designation patterns in transcriptome
      assemblies to maximize phylogenetic independence in downstream analysis. Results:
      When applied to previously studied spider transcriptomic data as well as
      simulated data, FUSTr successfully grouped coding sequences into proper gene
      families as well as correctly identified those under strong positive selection in
      relatively little time. Conclusions: FUSTr provides a useful tool for novice
      bioinformaticians to characterize the molecular evolution of organisms throughout
      the tree of life using large transcriptomic biodiversity datasets and can utilize
      multi-processor high-performance computational facilities.

PMID- 29372117
TI  - Expression status and clinical significance of lncRNA APPAT in the progression of
      atherosclerosis.
AB  - Background: Long non-coding RNAs (lncRNAs) have been reported to modulate
      cardiovascular diseases, and expression dynamics of lncRNAs in the bloodstream
      were proposed to be potential biomarkers for clinical diagnosis. However, few
      cardiovascular diseases-related circulating lncRNAs were identified and their
      prediction power has not been investigated in depth. Here we report a new
      circulating lncRNA, atherosclerotic plaque pathogenesis associated transcript
      (APPAT), and evaluated its role and predicting ability in atherosclerotic
      development. Methods: APPAT was analyzed and screened by high-throughput
      sequencing, and then detected in vitro and in vivo. Immunofluorescence
      fluorescence in situ hybridization (IF-FISH) was utilized to explore distribution
      and subcellular location of APPAT. The expressing alteration of APPAT in samples
      of healthy and pathological coronary artery was explored further. We also
      assessed the level of circulating APPAT in blood samples from healthy
      individuals, and patients with angina pectoris (AP) or myocardial infarction
      (MI). Additionally, we predicted and validated microRNA targets of APPAT, then
      showed the expression level of a candidate target which was primarily measured in
      human VSMCs cell line, coronary artery, and blood samples. Lastly, we examined
      the potential indicating ability of APPAT for the risk of AP or MI. Results:
      APPAT showed significant reduction in ox-LDL treated human VSMCs in vitro. It
      enriched in contractile VSMCs of artery tunica media and mainly existed in
      cytoplasm. Significant down-regulation of APPAT was found in coronary artery
      samples with severe stenosis. More importantly, we observed decreased expression
      of APPAT in blood samples accompanying disease progression. ROC and correlation
      analyses further verified the relatively high predicting ability of APPAT. We
      also observed the predicted miRNA exhibited opposite expression direction to that
      of APPAT. Conclusions: This study revealed that circulating lncRNA-APPAT may
      perform an important function and have some indicating ability on the development
      of atherosclerosis.

PMID- 29372118
TI  - Effects of chronic exposure to thiamethoxam on larvae of the hoverfly Eristalis
      tenax (Diptera, Syrphidae).
AB  - There is widespread concern over the use of neonicotinoid pesticides in the agro
      ecosystem, due in part to their high water solubility which can lead to
      widespread contamination of non-target areas including standing surface water.
      Most studies investigating the negative fitness consequences of neonicotinoids
      have focused on bees, with little research on the impact on other non-target
      insects. Here we examined the effect of exposure on the aquatic larval stages of
      the hoverfly Eristalis tenax L. (Diptera: Syrphidae) to a range of concentrations
      (control, 5, 15, 50, 100 and 500 ppb) of the neonicotinoid thiamethoxam; no
      published studies have thus far examined the effects of neonicotinoids on
      hoverflies. Survival was significantly lower when exposed to 500 ppb
      thiamethoxam, but this concentration exceeds that likely to be found in the
      field. We observed no effect on survival, development or any latent effects on
      adult activity budgets resulting from exposure to lower concentrations (up to 100
      ppb). Our results suggest that E. tenax exposed as larvae to thiamethoxam are
      unlikely to be negatively impacted by this neonicotinoid under field conditions.

PMID- 29372119
TI  - CoMiniGut-a small volume in vitro colon model for the screening of gut microbial
      fermentation processes.
AB  - Driven by the growing recognition of the influence of the gut microbiota (GM) on
      human health and disease, there is a rapidly increasing interest in understanding
      how dietary components, pharmaceuticals and pre- and probiotics influence GM. In
      vitro colon models represent an attractive tool for this purpose. With the dual
      objective of facilitating the investigation of rare and expensive compounds, as
      well as an increased throughput, we have developed a prototype in vitro parallel
      gut microbial fermentation screening tool with a working volume of only 5 ml
      consisting of five parallel reactor units that can be expanded with multiples of
      five to increase throughput. This allows e.g., the investigation of interpersonal
      variations in gut microbial dynamics and the acquisition of larger data sets with
      enhanced statistical inference. The functionality of the in vitro colon model,
      Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two
      common prebiotics using the oligosaccharide inulin and the disaccharide lactulose
      at 1% (w/v). We then investigated fermentation of the scarce and expensive human
      milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose
      and the more common Fructooligosaccharide in fermentations with infant gut
      microbial communities. Investigations of microbial community composition dynamics
      in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput
      sequencing showed excellent experimental reproducibility and allowed us to
      extract significant differences in gut microbial composition after 24 h of
      fermentation for all investigated substrates and fecal donors. Furthermore, short
      chain fatty acids (SCFAs) were quantified for all treatments and donors.
      Fermentations with inulin and lactulose showed that inulin leads to a microbiota
      dominated by obligate anaerobes, with high relative abundance of Bacteroidetes,
      while the more easily fermented lactulose leads to higher relative abundance of
      Proteobacteria. The subsequent study on the influence of HMOs on two infant GM
      communities, revealed the strongest bifidogenic effect for 3'SL for both infants.
      Inter-individual differences of infant GM, especially with regards to the
      occurrence of Bacteroidetes and differences in bifidobacterial species
      composition, correlated with varying degrees of HMO utilization foremost of 6'SL
      and 3'FL, indicating species and strain related differences in HMO utilization
      which was also reflected in SCFAs concentrations, with 3'SL and 6'SL resulting in
      significantly higher butyrate production compared to 3'FL. In conclusion, the
      increased throughput of CoMiniGut strengthens experimental conclusions through
      elimination of statistical interferences originating from low number of
      repetitions. Its small working volume moreover allows the investigation of rare
      and expensive bioactives.

PMID- 29372120
TI  - Social network community structure and the contact-mediated sharing of commensal
      E. coli among captive rhesus macaques (Macaca mulatta).
AB  - In group-living animals, heterogeneity in individuals' social connections may
      mediate the sharing of microbial infectious agents. In this regard, the genetic
      relatedness of individuals' commensal gut bacterium Escherichia coli may be ideal
      to assess the potential for pathogen transmission through animal social networks.
      Here we use microbial phylogenetics and population genetics approaches, as well
      as host social network reconstruction, to assess evidence for the contact
      mediated sharing of E. coli among three groups of captively housed rhesus
      macaques (Macaca mulatta), at multiple organizational scales. For each group,
      behavioral data on grooming, huddling, and aggressive interactions collected for
      a six-week period were used to reconstruct social network communities via the
      Data Cloud Geometry (DCG) clustering algorithm. Further, an E. coli isolate was
      biochemically confirmed and genotypically fingerprinted from fecal swabs
      collected from each macaque. Population genetics approaches revealed that Group
      Membership, in comparison to intrinsic attributes like age, sex, and/or matriline
      membership of individuals, accounted for the highest proportion of variance in E.
      coli genotypic similarity. Social network approaches revealed that such sharing
      was evident at the community-level rather than the dyadic level. Specifically,
      although we found no links between dyadic E. coli similarity and social contact
      frequencies, similarity was significantly greater among macaques within the same
      social network communities compared to those across different communities.
      Moreover, tests for one of our study-groups confirmed that E. coli isolated from
      macaque rectal swabs were more genotypically similar to each other than they were
      to isolates from environmentally deposited feces. In summary, our results suggest
      that among frequently interacting, spatially constrained macaques with complex
      social relationships, microbial sharing via fecal-oral, social contact-mediated
      routes may depend on both individuals' direct connections and on secondary
      network pathways that define community structure. They lend support to the
      hypothesis that social network communities may act as bottlenecks to contain the
      spread of infectious agents, thereby encouraging disease control strategies to
      focus on multiple organizational scales. Future directions includeincreasing
      microbial sampling effort per individual to better-detect dyadic transmission
      events, and assessments of the co-evolutionary links between sociality,
      infectious agent risk, and host immune function.

PMID- 29372121
TI  - Morphology and structure of Homo erectus humeri from Zhoukoudian, Locality 1.
AB  - Background: Regional diversity in the morphology of the H. erectus postcranium is
      not broadly documented, in part, because of the paucity of Asian sites preserving
      postcranial fossils. Yet, such an understanding of the initial hominin taxon to
      spread throughout multiple regions of the world is fundamental to documenting the
      adaptive responses to selective forces operating during this period of human
      evolution. Methods: The current study reports the first humeral rigidity and
      strength properties of East Asian H. erectus and places its diaphyseal
      robusticity into broader regional and temporal contexts. We estimate true cross
      sectional properties of Zhoukoudian Humerus II and quantify new diaphyseal
      properties of Humerus III using high resolution computed tomography. Comparative
      data for African H. erectus and Eurasian Late Pleistocene H. sapiens were
      assembled, and new data were generated from two modern Chinese populations.
      Results: Differences between East Asian and African H. erectus were
      inconsistently expressed in humeral cortical thickness. In contrast, East Asian
      H. erectus appears to exhibit greater humeral robusticity compared to African H.
      erectus when standardizing diaphyseal properties by the product of estimated body
      mass and humeral length. East Asian H. erectus humeri typically differed less in
      standardized properties from those of side-matched Late Pleistocene hominins
      (e.g., Neanderthals and more recent Upper Paleolithic modern humans) than did
      African H. erectus, and often fell in the lower range of Late Pleistocene humeral
      rigidity or strength properties. Discussion: Quantitative comparisons indicate
      that regional variability in humeral midshaft robusticity may characterize H.
      erectus to a greater extent than presently recognized. This may suggest a
      temporal difference within H. erectus, or possibly different ecogeographical
      trends and/or upper limb loading patterns across the taxon. Both discovery and
      analysis of more adult H. erectus humeri are critical to further evaluating and
      potentially distinguishing between these possibilities.

PMID- 29372122
TI  - Alpha-actinin of the chlorarchiniophyte Bigelowiella natans.
AB  - The genome of the chlorarchiniophyte Bigelowiella natans codes for a protein
      annotated as an alpha-actinin-like protein. Analysis of the primary sequence
      indicate that this protein has the same domain structure as other alpha-actinins,
      a N-terminal actin-binding domain and a C-terminal calmodulin-like domain. These
      two domains are connected by a short rod domain, albeit long enough to form a
      single spectrin repeat. To analyse the functional properties of this protein, the
      full-length protein as well as the separate domains were cloned and isolated.
      Characerisation showed that the protein is capable of cross-linking actin
      filaments into dense bundles, probably due to dimer formation. Similar to human
      alpha-actinin, calcium-binding occurs to the most N-terminal EF-hand motif in the
      calmodulin-like C-terminal domain. The results indicate that this Bigelowiella
      protein is a proper alpha-actinin, with all common characteristics of a typical
      alpha-actinin.

PMID- 29372124
TI  - The French press: a repeatable and high-throughput approach to exercising
      zebrafish (Danio rerio).
AB  - Zebrafish are increasingly used as a vertebrate model organism for various traits
      including swimming performance, obesity and metabolism, necessitating high
      throughput protocols to generate standardized phenotypic information. Here, we
      propose a novel and cost-effective method for exercising zebrafish, using a
      coffee plunger and magnetic stirrer. To demonstrate the use of this method, we
      conducted a pilot experiment to show that this simple system provides repeatable
      estimates of maximal swim performance (intra-class correlation [ICC] = 0.34-0.41)
      and observe that exercise training of zebrafish on this system significantly
      increases their maximum swimming speed. We propose this high-throughput and
      reproducible system as an alternative to traditional linear chamber systems for
      exercising zebrafish and similarly sized fishes.

PMID- 29372123
TI  - The importance of local settings: within-year variability in seawater temperature
      at South Bay, Western Antarctic Peninsula.
AB  - The Western Antarctic Peninsula (WAP) has undergone significant changes in air
      and seawater temperatures during the last 50 years. Although highly stenotherm
      Antarctic organisms are expected to be severely affected by the increase of
      seawater temperature, high-resolution datasets of seawater temperature within
      coastal areas of the WAP (where diverse marine communities have been reported)
      are not commonly available. Here we report on within-year (2016-2017) variation
      in seawater temperature at three sites on Doumer Island, Palmer Archipelago, WAP.
      Within a year, Antarctic organisms in South Bay were exposed to water
      temperatures in excess of 2  degrees C for more than 25 days and 2.5  degrees C
      for more than 10 days. We recorded a temperature range between -1.7 degrees  to
      3.0  degrees C. Warming of seawater temperature was 3.75 times faster after
      October 2016 than it was before October. Results from this study indicate that
      organisms at South Bay are already exposed to temperatures that are being used in
      experimental studies to evaluate physiological responses to thermal stress in WAP
      organisms. Continuous measurements of short to long-term variability in seawater
      temperature provides important information for parametrizing meaningful
      experimental treatments that aim to assess the local effects of environmental
      variation on Antarctic organisms under future climate scenarios.

PMID- 29372126
TI  - An Atypical Clinical Presentation of Post-traumatic Syringomyelia: A Case Report
      and Brief Review of the Literature.
AB  - Syringomyelia classically presents as a bilateral sensory loss of the dissociated
      type which includes the loss of pain and temperature with the preservation of
      fine touch, vibratory sensation, and proprioception in the shoulder, arm, and
      hand. Eventually, weakness of the legs, muscle wasting, and ataxia can also be
      seen due to the involvement of the corticospinal tracts and the posterior columns
      of the spinal cord. We present the case of a 64-year-old patient with an atypical
      presentation of post-traumatic syringomyelia. This atypical presentation included
      a unilateral sensory loss of fine touch, pain, and temperature in the shoulder,
      arm, and hand which was of the non-dissociated type with no weakness, muscular
      atrophy, loss of vibratory sensation, or proprioception.

PMID- 29372125
TI  - Dilated Thoracic Esophagus Presenting with Painful Progressive Persistent
      Dysphagia and Leukocytosis of Unknown Origin.
AB  - Esophageal cancer is the eighth-most common cause of cancer-related mortality
      worldwide. The most common presenting symptom in advanced distal esophageal
      cancer is the sensation of sticking food, but it may sometimes present with
      bleeding and related complications, or asymptomatic leukocytosis. We present the
      case of a 77-year-old afebrile man with chronic alcoholism and a dilated thoracic
      esophagus with painful, progressive, and persistent dysphagia and leukocytosis of
      unknown origin. A 77-year-old man with a past medical history of hypertension and
      colonic cancer status post right hemicolectomy (surveillance negative) presented
      to the emergency department with painful, progressive, persistent, and worsening
      dysphagia for the past three weeks. It was associated with an unintentional
      weight loss of ten pounds in one month and nausea with non-bilious and non-bloody
      vomiting for several days. He denied fever, diarrhea, hoarseness of voice, change
      in bowel movement, hematemesis, hematochezia, melena, orthopnea, dyspnea at rest,
      palpitation, and abdominal pain. A chest x-ray (lateral view) showed debris in a
      dilated thoracic esophagus with fluid. An esophagogram showed a 10 x 3 cm
      obstructive mass with irregular mucosa within the proximal esophagus from the
      thoracic vertebra levels four to ten. A computed tomography scan of the chest
      with contrast showed long segment dilatation of the upper and mid-thoracic
      esophagus with generalized circumferential thickening of the distal esophagus. He
      was empirically on cefazolin and metronidazole but later switched to
      piperacillin, tazobactam, and fluconazole. Cardiac risk stratification was done
      for an esophagogastroduodenoscopy. However, the patient and the family opted for
      palliative care and agreed to a do-not-resuscitate/do-not-intubate status. In
      esophageal cancers, tumor-related leukocytosis and neutrophilia are common
      presentations. However, there is no standardized routine screening test for
      esophageal cancers. Thus, when asymptomatic afebrile elderly patients present
      with leukocytosis of unknown origin, clinicians should have suspicions of occult
      malignancy such as esophageal cancers, gastric cancer, and pancreatic cancer.

PMID- 29372127
TI  - "False" Ligaments: A Review of Anatomy, Potential Function, and Pathology.
AB  - This paper, although not an exhaustive review of "false" ligaments in the body,
      describes eight such ligaments. False ligaments are defined as ligamentous
      structures connecting separate parts of the same bone and are thus immobile. The
      ligaments reviewed include the suprascapular ligament, the transforaminal lumbar
      ligaments, the mamillo-accessory ligament, the transverse atlantal ligament, the
      transverse occipital ligament, the transverse humeral ligament, the
      coracoacromial ligament, and the transverse part of the ulnar collateral
      ligament. In this review, the anatomy and histological characteristics of each
      ligament are reviewed. Furthermore, possible functions and associated pathologies
      are described.

PMID- 29372128
TI  - Ticking Bomb: Asymptomatic Mirizzi Syndrome.
AB  - Mirizzi syndrome, also known as extrinsic biliary compression syndrome, is a rare
      clinical entity in which the common bile duct is obstructed by compression by the
      impaction of one or more gallstones in the cystic duct or gallbladder
      infundibulum. This case illustrates an absolutely asymptomatic presentation of
      Mirizzi syndrome in a 62-year-old, otherwise healthy, woman. Mirizzi syndrome was
      treated with preemptive laparotomy cholecystectomy. The present case is exemplary
      for careful evaluation with the proper index of suspicion in establishment of
      preoperative diagnosis as well as prompt treatment prior to development of
      complications.

PMID- 29372129
TI  - Biomechanics of an Expandable Lumbar Interbody Fusion Cage Deployed Through
      Transforaminal Approach.
AB  - Introduction: A novel expandable lumbar interbody fusion cage has been developed
      which allows for a broad endplate footprint similar to an anterior lumbar
      interbody fusion (ALIF); however, it is deployed from a minimally invasive
      transforaminal unilateral approach. The perceived benefit is a stable
      circumferential fusion from a single approach that maintains the anterior tension
      band of the anterior longitudinal ligament.The purpose of this biomechanics
      laboratory study was to evaluate the biomechanical stability of an expandable
      lumbar interbody cage inserted using a transforaminal approach and deployed in
      situ compared to a traditional lumbar interbody cage inserted using an anterior
      approach (control device). Methods: Twelve cadaveric spine specimens (L1-L5) were
      tested intact and after implantation of both the control and experimental devices
      in two (L2-L3 and L3-L4) segments of each specimen; the assignments of the
      control and experimental devices to these segments were alternated. Effect of
      supplemental pedicle screw-rod stabilization was also assessed. Moments were
      applied to the specimens in flexion-extension (FE), lateral bending (LB), and
      axial rotation (AR). The effect of physiologic preload on construct stability was
      evaluated in FE. Segmental motions were measured using an optoelectronic motion
      measurement system. Results: The deployable expendable TLIF cage and control
      devices significantly reduced FE motion with and without compressive preload when
      compared to the intact condition (p<0.05). Segmental motions in LB and AR were
      also significantly reduced with both devices (p<0.05). Under no preload, the
      deployable expendable TLIF cage construct resulted in significantly smaller FE
      motion compared to the control cage construct (p<0.01). Under all other testing
      modes (FE under 400N preload, LB, and AR) the postoperative motions of the two
      constructs did not differ statistically (p>0.05). Adding bilateral pedicle screws
      resulted in further reduction of ROM for all loading modes compared to intact
      condition, with no statistical difference between the two constructs (p>0.05).
      Conclusions: The ability of the deployable expendable interbody cage in reducing
      segmental motions was equivalent to the control cage when used as a stand-alone
      construct and also when supplemented with bilateral pedicle screw-rod
      instrumentation. The larger footprint of the fully deployed TLIF cage combined
      with preservation of the anterior soft-tissue tension band may provide a better
      biomechanical fusion environment by combining the advantages of the traditional
      ALIF and TLIF approaches.

PMID- 29372130
TI  - Tethered Cord as a Complication of Chronic Cerebral Spinal Fluid Diversion.
AB  - Introduction: The etiology and treatment of tethered cord syndrome remains
      controversial, especially in adults. We present an unusual case of tethered cord
      syndrome with an associated epidural lipomatosis likely due to chronic over
      shunting of cerebrospinal fluid (CSF). Methods: A 25-year-old woman had a history
      of Chiari malformation, hydrocephalus, and a ventriculoperitoneal shunt. She
      demonstrated progressively worsening gait, which led to a diagnosis of myelopathy
      and a posterior cervical decompression and fusion was performed. Imaging revealed
      engorgement of the epidural veins ventral to the spinal cord which was causing
      cord compression. Magnetic resonance (MR) imaging of the lumbar spine
      demonstrated a low-lying conus at the level of L2-L3 with an absence of CSF in
      the lumbar cistern. This was associated with this was a widening of the epidural
      space with secondary epidural lipomatosis. She underwent a laminectomy of L5 as
      well as decompression of the inferior aspect of the L4 and superior aspect of the
      S1 lamina. No free flow of CSF could ever be appreciated as was suggested by
      postoperative MR imaging. Postoperatively, the patient did well and was
      discharged in stable condition. Conclusion: Tethering of the spinal cord,
      associated with epidural lipomatosis, may be secondary to over-drainage of CSF.
      Symptoms of back pain and tethered cord phenomenon may warrant surgical
      intervention.

PMID- 29372131
TI  - Tranexamic Acid Reduced the Percent of Total Blood Volume Lost During Adolescent
      Idiopathic Scoliosis Surgery.
AB  - Background: Multilevel posterior spine fusion is associated with significant
      intraoperative blood loss. Tranexamic acid is an antifibrinolytic agent that
      reduces intraoperative blood loss. The goal of this study was to compare the
      percent of total blood volume lost during posterior spinal fusion (PSF) with or
      without tranexamic acid in patients with adolescent idiopathic scoliosis (AIS).
      Methods: Thirty-six AIS patients underwent PSF in 2011-2014; the last half (n=18)
      received intraoperative tranexamic acid. We retrieved relevant demographic,
      hematologic, intraoperative and outcomes information from medical records. The
      primary outcome was the percent of total blood volume lost, calculated from
      estimates of intraoperative blood loss (numerator) and estimated total blood
      volume per patient (denominator, via Nadler's equations). Unadjusted outcomes
      were compared using standard statistical tests. Results: Tranexamic acid and no
      tranexamic acid groups were similar (all p>0.05) in mean age (16.1 vs. 15.2
      years), sex (89% vs. 83% female), body mass index (22.2 vs. 20.2 kg/m2),
      preoperative hemoglobin (13.9 vs. 13.9 g/dl), mean spinal levels fused (10.5 vs.
      9.6), osteotomies (1.6 vs. 0.9) and operative duration (6.1 hours, both). The
      percent of total blood volume lost (TBVL) was significantly lower in the
      tranexamic acid-treated vs. no-tranexamic acid group (median 8.23% vs. 14.30%, p
      = 0.032); percent TBVL per level fused was significantly lower with tranexamic
      acid than without it (1.1% vs. 1.8%, p=0.048). Estimated blood loss (milliliters)
      was similar across groups. Conclusions: Tranexamic acid significantly reduced the
      percentage of total blood volume lost versus no tranexamic acid in AIS patients
      who underwent PSF using a standardized blood loss measure.Level of Evidence: 3.
      Institutional Review Board status: This medical record chart review (minimal
      risk) study was approved by the University of Minnesota Institutional Review
      Board.

PMID- 29372132
TI  - Comparison of quality of life between men and women who underwent Transforaminal
      Percutaneous Endoscopic Discectomy for lumbar disc herniation.
AB  - Background: Studies describing the efficacy of TPED on shortness of recovery and
      improvement of postoperative quality of life are limited, especially regarding
      gender something that has never been reported before in the literature. The
      purpose of this study is to evaluate possible differences of the health-related
      quality of life in patients who underwent TPED for LDH in accordance with sex.
      Methods: Seventy-six patients diagnosed and treated with TPED for LDH with 1 year
      follow-up were selected and divided into two groups of equal number depending on
      sex. Their quality of life was evaluated by using the SF-36 before the operation,
      six weeks, three, six and twelve months postoperatively. A statistical analysis
      was conducted, in order to compare the 8 scaled scores of the SF-36 combining
      each time two chronological phases in the total of patients, in each group and
      between groups. Results: Fifty-two (68.4%) patients were <=63 years old, while
      the rest 24 (31,4%) were >63 years old (mean +/-SD = 56,5 +/-12,1 years). Apart
      from the PF domain, the scores were higher in every visit for the two groups, but
      the change between groups was not significant. Women had a significantly higher
      increase of PF score in 3 months after TPED and in the interval 6 weeks-3 months
      comparing with men. However, in the intervals 3 months-6 months and 3 months-12
      months men presented significantly higher increase compared to women.
      Conclusions: Statistically significant improvement of the quality of life for
      both men and women was observed. Generally, there was no significant difference
      between the two groups. As regards to the physical functioning, it appears to be
      a significant difference which is counterpoised over time. Level of evidence: 2.
      Clinical relevance: TPED for LDH does not present major differences in the
      improvement of quality of life regarding gender.

PMID- 29372133
TI  - The Effect of Smoking on Spinal Fusion.
AB  - Background: Spinal fusion surgery is performed about half a million times per
      year in the United States and millions more worldwide. It is an effective method
      for reducing pain, increasing stability, and correcting deformity in patients
      with various spinal conditions. In addition to being a well-established risk
      factor for a variety of medical conditions, smoking has deleterious effects on
      the bone healing of spinal fusions. This review aims to specifically analyze the
      ways in which smoking affects the outcomes of spinal fusion and to explore ways
      in which these negative consequences can be avoided. Purpose: This article
      provides a complete understanding of the ways smoking affects spinal fusion from
      a biochemical and clinical perspective. Recommendations are also provided for
      ways in which surgeons can limit patient exposure to the most serious negative
      outcomes associated with cigarette smoking. Study Design/Setting: This study was
      a retrospective literature review done using the NCBI database. The research was
      compiled at NYU Hospital for Joint Diseases and the NYU Center for
      Musculoskeletal Care. Methods: A comprehensive literature review was done
      spanning research on a variety of subjects related to smoking and spinal fusion
      surgery. The biochemistry of smoking and fusion healing were examined in great
      detail. In addition, both in vivo animal studies and human clinical studies were
      evaluated to explore fusion success related to the effects of smoking and its
      biochemical factors on spinal fusion surgery. Results: Smoking significantly
      increases the risk of pseudoarthrosis for patients undergoing both lumbar and
      cervical fusions. In addition to nonunion, smoking also increases the risk of
      other perioperative complications such as infection, adjacent-segment pathology,
      and dysphagia. Treatment options are available that can be explored to reduce the
      risk of smoking-related morbidity, such as nicotine replacement therapy and use
      of bone morphogenetic proteins (BMPs). Conclusions: It has been clearly
      demonstrated from both a biochemical and clinical perspective that smoking
      increases the rate of perioperative complications for patients undergoing spinal
      fusion surgery, particularly pseudoarthosis. It has also been shown that there
      are certain approaches that can reduce the risk of morbidity. The most important
      recommendation is smoking cessation for four weeks after surgery. In addition,
      patients may be treated with certain surgical techniques, including the use of
      BMPs, to reduce the risk of pseudoarthrosis. Lastly, nicotine replacement therapy
      is an area of continued interest in relation to spinal fusion outcomes and more
      research needs to be done to determine its efficacy moving forward.

PMID- 29372134
TI  - A Rare Case of T1-2 Thoracic Disc Herniation Mimicking Cervical Radiculopathy.
AB  - Introduction: Thoracic disc herniation is not as common as other disc herniations
      seen at other levels of spinal column. Th1-Th2 disc herniation is an extremely
      rare condition. Physical and cautious radiological examination is significantly
      important for diagnosis. Case Presentation: We report a 45 years old male case
      with complaint of neck pain radiating to right upper extremity. The physical
      examination revealed Th1 radiculopathy symptoms. According to his images
      degeneration at C6-7 level and right T1 root compression due to Th1-Th2 disc
      herniation at foraminal region were evaluated. The patient underwent
      hemilaminectomy, foraminatomy and discectomy at T1-T2 level via posterior
      approach. Conclusion: T1-2 level thoracic disc herniation can accompany with
      cervical region problems and some syndromes can mimic Th1 radiculopathy symptoms.
      The aim of this case report is to keep on mind of this rare condition and to
      emphasize the importance of physical findings and correlations with magnetic
      resonance imaging.

PMID- 29372135
TI  - Long-term Evaluation of Cervical Disc Arthroplasty with the Mobi-C(c) Cervical
      Disc: A Randomized, Prospective, Multicenter Clinical Trial with Seven-Year
      Follow-up.
AB  - Background: Cervical total disc replacement (TDR) is an increasingly accepted
      procedure for the treatment of symptomatic cervical degenerative disc disease.
      Multiple Level I evidence clinical trials have established cervical TDR to be a
      safe and effective procedure in the short-term. The objective of this study is to
      provide a long-term assessment of TDR versus anterior discectomy and fusion for
      the treatment of one- and two-level disc disease. Methods: This study was a
      continuation of a prospective, multicenter, randomized, US FDA IDE clinical trial
      comparing cervical TDR with the Mobi-C(c) Cervical Disc versus ACDF through 7
      years follow-up. Inclusion criteria included a diagnosis of symptomatic cervical
      degenerative disc disease at one or two cervical levels. TDR patients were
      treated using a Mobi-C(c) artificial disc (Zimmer Biomet, Austin TX, USA). ACDF
      with allograft and anterior plate was used as a control treatment. Outcome
      measures were collected preoperatively and postoperatively at 6 weeks, at 3, 6,
      12, 18 months, annually through 60 months, and at 84 months. Measured outcomes
      included Overall success, Neck Disability Index (NDI), VAS neck and arm pain,
      segmental range of motion (ROM), patient satisfaction, SF-12 MCS/PCS, major
      complications, and subsequent surgery rate. The primary endpoint was an FDA
      composite definition of success comprising clinical improvement and an absence of
      major complications and secondary surgery events. Results: A total of 599
      patients were enrolled and treated, with 164 treated with one-level TDR, 225
      treated with two-level TDR, 81 treated with one-level ACDF, and 105 treated with
      two-level ACDF. At seven years, follow-up rates ranged from 73.5% to 84.4%
      (overall 80.2%).The overall success rates of two level TDR and ACDF patients were
      60.8% and 34.2%, respectively (p<0.0001). The overall success rates of one level
      TDR and ACDF patients were 55.2% and 50%, respectively (p>0.05). Both the single
      and two level TDR and ACDF groups showed significant improvement from baseline
      NDI scores, VAS neck and arm pain scores, and SF-12 MCS/PCS scores (p<0.0001). In
      the single level cohort, there was an increased percentage of TDR patients who
      reported themselves as "very satisfied" (TDR 90.9% vs ACDF 77.8%; p= 0.028).
      There was a lower rate of adjacent level secondary surgery in the single level
      TDR patients (3.7%) versus the ACDF patients (13.6%; p = 0.007).In the two level
      TDR group, the NDI success rate was significantly greater in the TDR group (TDR:
      79.0% vs. ACDF: 58.0%; p=0.001). There was significantly more improvement in NDI
      change score at 7 years in the TDR patients versus ACDF. The TDR group had a
      significantly higher rate of patients who were "very satisfied" with their
      treatment compared to the ACDF group (TDR: 85.9% vs. ACDF: 73.9%). The rate of
      subsequent surgery at the index level was significantly lower in the TDR group
      compared to the ACDF group (TDR: 4.4% vs. ACDF: 16.2%; p=0.001). The rate of
      adjacent level secondary surgery was significantly lower in the two level TDR
      (4.4%) patients compared to the ACDF (11.3%; p=0.03) patients. In both single and
      two level cohorts, the percentage of patients with worse NDI (2.5%-3.8% of two
      level surgeries and 1.2%-2.5% of single level surgeries) or worse neck pain (5%
      6.8% of the two level surgeries and 1.3% - 3.8% of the single level surgeries)
      was strikingly low in both groups but trended lower in the TDR patients.
      Conclusions: At seven years, the composite success analysis demonstrated clinical
      superiority of two level TDR over ACDF and non-inferiority of single level TDR
      versus ACDF. There were lower rates of secondary surgery and higher adjacent
      level disc survivorship in both groups. Both surgeries were remarkably effective
      in alleviating pain relative to baseline and the rate of patients with worse
      disability or neck pain was surprisingly low. Overall, greater than 95% of
      patients (from both groups) who underwent TDR and 88% of patients who underwent
      ACDF were "very satisfied" at seven years. The differences in clinical
      effectiveness of TDR versus ACDF becomes more apparent as treatment increases
      from one to two levels, indicating a significant benefit for TDR over ACDF for
      two-level procedures. Ethical Standards: The Mobi-C Clinical Trial
      (ClinicalTrials.gov registration number: NCT00389597) was conducted at 24 sites
      in the US and was approved by the Institutional Review Board, Research Ethics
      Committee, or local equivalent of each participating site. Level of Evidence: 1.

PMID- 29372136
TI  - A Comparison of Three Different Methods of Fixation in the Management of
      Thoracolumbar Fractures.
AB  - Introduction: Management of thoracolumbar fractures remains controversial in the
      literature. The primary aims of this study were to assess different levels of
      fixation with respect to radiological outcomes in terms of fracture reduction and
      future loss of correction. Methods: This is a single center, retrospective study.
      Fifty-five patients presenting with thoracolumbar fractures between January 2012
      and December 2015 were analyzed in the study. The levels of fixation were divided
      in 3 groups, 1 vertebra above and 1 below the fracture (1/1), 2 above and 2 below
      (2/2), and 2 above and 1 below (2/1). Results: The most common mechanism was high
      fall injury and the most common vertebra L1. Burst fractures were the ones with
      the highest incidence. The 2/2 fixation achieved the best reduction of the
      fracture but with no statistical significance. The correction is maintained
      better by the 2/2 fixation but there is no statistical difference compared to the
      other fixations. Insertion of screws at the fracture level did not improve
      outcomes. Conclusion: The data of this study identified a trend towards better
      radiological outcomes for fracture reduction and maintenance of the correction in
      the 2/2 fixations. However these results are not statistically significant.
      Future multicenter prospective clinical trials are needed in order to agree on
      the ideal management and method of fixation for thoracolumbar fractures.

PMID- 29372137
TI  - Demographic Trends in the Use of Intraoperative Neuromonitoring for Scoliosis
      Surgery in the United States.
AB  - Background: Intraoperative neuromonitoring (ION) such as motor-evoked potential
      (MEP), somatosensory evoked potentials (SSEP) and electromyography (EMG) are used
      to detect impending neurological injuries during spinal surgery. To date, little
      is known on the trends in the use of ION for scoliosis surgery in the United
      States. Methods: A retrospective review was performed using the PearlDiver
      Database to identify patients that had scoliosis surgery with and without ION
      from years 2005 to 2011. Demographic information (such as age, gender, region
      within the United States) and clinical information (such as type of ION and rates
      of neurological injury) were assessed. Results: There were 3618 patients who had
      scoliosis surgery during the study period. ION was used in 1361 (37.6%) of these
      cases. The number of cases in which ION was used increased from 27% in 2005 to
      46.9% in 2011 (p < 0.0001). Multimodal ION was used more commonly than unimodal
      ION (64.6% vs. 35.4%). The most commonly used modality was combined SSEP and EMG
      while the least used modality was MEP only. Neurological injuries occurred in
      1.8% and 2.0% of patients that had surgery with and without ION, respectively (p
      = 0.561). ION was used most commonly in patients < 65 years of age and in the
      Northeastern part of the United States (age; p = 0.006, region; p < 0.0001).
      Conclusions: The use of ION for scoliosis surgery gradually increased annually
      from 2005 to 2011. Age and regional differences were noted with neuromonitoring
      being most commonly used for scoliosis surgery in non-elderly patients and in the
      Northeastern part of the United States. No differences were noted in the risk of
      neurological injury in patients that had surgery with and without ION. Although
      the findings from this study may seem to suggest that ION may not influence the
      risk of neurologic injury, this result must be interpreted with caution as
      inherently riskier surgeries may utilize ION more, leading to an actual reduction
      in injuries more dramatic than observed in this study.

PMID- 29372138
TI  - Surgeon Reliability for the Assessment of Lumbar Spinal Stenosis on MRI: The
      Impact of Surgeon Experience.
AB  - Background: Treating surgeon's visual assessment of axial MRI images to ascertain
      the degree of stenosis has a critical impact on surgical decision-making. The
      purpose of this study was to prospectively analyze the impact of surgeon
      experience on inter-observer and intra-observer reliability of assessing severity
      of spinal stenosis on MRIs by spine surgeons directly involved in surgical
      decision-making. Methods: Seven fellowship trained spine surgeons reviewed MRI
      studies of 30 symptomatic patients with lumbar stenosis and graded the stenosis
      in the central canal, the lateral recess and the foramen at T12-L1 to L5-S1 as
      none, mild, moderate or severe. No specific instructions were provided to what
      constituted mild, moderate, or severe stenosis. Two surgeons were "senior"
      (>fifteen years of practice experience); two were "intermediate" (>four years of
      practice experience), and three "junior" (< one year of practice experience). The
      concordance correlation coefficient (CCC) was calculated to assess inter-observer
      reliability. Seven MRI studies were duplicated and randomly re-read to evaluate
      inter-observer reliability. Results: Surgeon experience was found to be a strong
      predictor of inter-observer reliability. Senior inter-observer reliability was
      significantly higher assessing central(p<0.001), foraminal p=0.005 and lateral
      p=0.001 than "junior" group.Senior group also showed significantly higher inter
      observer reliability that intermediate group assessing foraminal stenosis
      (p=0.036). In intra-observer reliability the results were contrary to that found
      in inter-observer reliability. Conclusion: Inter-observer reliability of
      assessing stenosis on MRIs increases with surgeon experience. Lower intra
      observer reliability values among the senior group, although not clearly
      explained, may be due to the small number of MRIs evaluated and quality of MRI
      images.Level of evidence: Level 3.

PMID- 29372139
TI  - Validity and reliability of a novel patient reported outcome tool to evaluate
      post-operative dysphagia, odynophagia, and voice (DOV) disability after anterior
      cervical procedures.
AB  - Background: Existing evaluative instruments for dysphagia, odynophagia, and voice
      disturbance are cumbersome, focus pre-dominately on dysphagia, and often require
      administration by a certified Speech Pathologist. This study was conducted to
      utilize widely accepted instruments such as the American Speech and Hearing
      Association's National Outcomes Measurement System (NOMS) and VAS pain scales to
      validate a novel, patient-reported instrument that quantifies the severity of
      post-operative dysphagia, odynophagia, and voice disabilities (DOV). Methods: The
      DOV was developed and subjected to multiple rounds of face and content validation
      by representative patient cohorts and a panel of clinical experts. An
      established, prospective clinical registry was utilized to collect pre and post
      operative VAS-swallow related pain and DOV measurements for subjects with recent
      anterior cervical procedures (n=25 content validation, n=20 criterion
      validation), or recent lumbar decompressions (n=33). NOMS evaluations were
      performed by a certified Speech Language Pathologist on the first post-operative
      day after minimally invasive anterior approaches to cervical reconstruction were
      performed in the criterion validation cohort. Results: Content validity: Subjects
      with a recent anterior cervical procedure reported a significant increase in post
      operative dysphagia (pre-op: 0.13+/-0.35, post-op: 1.08+/-1.41, p=0.01),
      odynophagia (pre-op: 0.24+/-0.69, post-op: 0.84+/-0.90, p=0.001), and voice (pre
      op: 0.10+/-0.41, post-op: 0.88+/-0.92, p=0.0004) disturbance. In contrast,
      subjects with a recent lumbar procedure did not demonstrate a significant
      increase in post-operative dysphagia, odynophagia, or voice disturbance
      (p>0.05).Criterion validity: Chi-squared contingency testing for independence
      between converted NOMS and DOV instrument scores accepted linkage between the two
      instruments for dysphagia X2(DF: 12, n=20, Expected: 21.03, Observed: 24.4, p:
      0.02) and voice X2(DF: 6, n=20, Expected: 12.60, Observed: 21.28, p: 0.002)
      dimensions. Similarly, converted swallow related VAS and DOV odynophagia
      instruments demonstrated linkage X2(DF: 9, n=20, Expected: 16.92, Observed:
      24.21, p: 0.004).Internal Reliability: Chronbach's alpha coefficient of
      reliability was 0.74 between all DOV survey dimensions. Conclusions: The DOV
      survey is a valid patient-reported instrument to rapidly and reliably detect post
      operative swallow and voice dysfunction.

PMID- 29372140
TI  - Enhancing evaluation of cervical spine: Thresholds for normal CT relationships in
      the subaxial cervical spine.
AB  - Background: Very little normative CT scan data exist defining expected
      relationships of vertebral structures in the intact cervical spine. Better
      understanding of normal relationships should improve sensitivity of injury
      detection, particularly for facet subluxation. The purpose of this paper was to
      describe the normal anatomical relationships and most sensitive measurements to
      detect abnormal alignment in the subaxial cervical spine. Methods: A group of 30
      CT scans with no documented cervical spine injury were utilized from an
      established data base in a trauma population. Twenty-two anatomical measurements
      were made for each level of the subaxial cervical spine using Microview software.
      For the purposes of measurement, the upper confidence limit of normal was
      reported as two standard deviations from the mean. Results: The novel, CT based
      measurements of bone articulation were generally smaller and had lower confidence
      intervals compared to traditional radiographic measurements of midline structures
      (such as interspinous distance, interlaminar widening, disc space widening). The
      upper limit of normal of facet joint height was reported (1.54mm anterior, 1.27mm
      posterior, and 2.0mm midportion) which may help identify distractive-flexion
      injuries. The upper limit of normal vertebral translation (2.0mm) was also
      reported to identify translation/rotation injuries. Conclusions: Normal CT
      measurements for the subaxial cervical spine, especially in the facets, were
      found to have small confidence limits and variation. Based upon these findings,
      we conclude that facet measurements and translation may be better screening tools
      than traditional radiographic criteria based upon midline structures. Using these
      measurements may improve detection of cervical spine injuries warranting further
      imaging or investigation and reducing missed injuries. Clinical Relevance:
      Improved understanding of normal anatomic measures in the subaxial spine will
      allow for better screening and identification of injuries. Ethical Statement:
      This was approved by the Office of Research Institutional Review Board, Baylor
      College of Medicine.

PMID- 29372142
TI  - Corrigendum: HmsC Controls Yersinia pestis Biofilm Formation in Response to Redox
      Environment.
AB  - [This corrects the article on p. 355 in vol. 7, PMID: 28848715.].

PMID- 29372141
TI  - Minimally Invasive Excision of Lumbar Tophaceous Gout: Case Report.
AB  - Background: Symptomatic spinal gout is relatively rare. Open laminectomy, with or
      without fusion, has been so far the standard treatment for symptomatic spinal
      gout. We describe here the first case of spinal tophaceus gout treated with
      minimally invasive surgery. Methods: A 60-year-old patient, morbidly obese, with
      no previous history of gout, presented with neurogenic claudication due to severe
      lumbar canal stenosis at L3/4. Surgery was performed through a minimally invasive
      approach, using tubular retractors. During surgery, an extradural mass with a
      thin capsule and containing white "chalky" partially calcified material, slightly
      adherent to and compressing the theca, was removed. Results: There were no intra-
      or perioperative complications. Surgery successfully improved the functional
      status, with a significant increase in walking distance and no residual leg pain
      or neurogenic claudication. Histopathology confirmed the diagnosis of spinal
      tophaceous gout. Conclusions/Level of evidence: Although spinal gout is usually
      responsive to medical treatment, surgery is often the first line treatment,
      particularly in patients with neurological deficits. Would surgery be indicated,
      we believe that minimally invasive surgery can be effective in treating
      symptomatic spinal tophaceous gout. Level of Evidence: Class IV.

PMID- 29372143
TI  - Colposcopy at a turning point.
AB  - For women who have abnormal Pap test results, the biopsy under colposcopic
      evaluation is the gold standard for determining the treatment modality. To
      increase the effectiveness of colposcopic communication, the International
      Federation for Cervical Pathology and Colposcopy (IFCPC) recently published
      fourth new nomenclature, aiming to create an evidence-based terminology. To
      increase the diagnostic accuracy of colposcopy, multiple biopsies of two or more
      sites are recommended. Recently, with the introduction of human papillomavirus
      (HPV) vaccine for cervical cancer prevention, pre-cancerous diseases caused by
      virus types 16 and 18 have been reduced, which is expected to reduce the number
      of colposcopic examinations and make colposcopic diagnosis more difficult.

PMID- 29372144
TI  - Antenatal corticosteroids and outcomes of preterm small-for-gestational-age
      neonates in a single medical center.
AB  - Objective: This study investigated the effect of an antenatal corticosteroid
      (ACS) in preterm small-for-gestational-age (SGA) neonate. Methods: This study was
      a retrospective cohort study. We compared women who received ACS with unexposed
      controls and evaluated neonatal complications among those having a singleton SGA
      neonate born between 29 and 34 complete gestational weeks. The neonates born
      after 32 weeks of gestation were divided into subgroups. Multivariable logistic
      regression analysis was performed. Results: A total 82 of the preterm infants met
      inclusion criteria; 57 (69.5%) were born after 32 weeks of gestation. There were
      no significant differences in terms of mechanical ventilation, seizure,
      intracranial hemorrhage, retinopathy of prematurity, necrotizing enterocolitis,
      feeding difficulty, and neonatal mortality between infants whose mothers received
      ACS ant those whose mothers did not (all P>0.05). However, newborns whose mothers
      received ACS exhibited a significantly increased risk of developing respiratory
      distress syndrome (RDS) (adjusted odds ratio [aOR], 3.271; 95% confidence
      interval [CI], 1.038-10.305; P=0.043). In case of neonates born beyond 32 weeks
      of gestation, the risk of neonatal hypoglycemia was significantly higher in women
      receiving ACS after controlling for confounding factors (aOR, 5.832; 95% CI,
      1.096-31.031; P=0.039). Conclusion: ACS did not improve neonatal morbidities, in
      SGA neonates delivered between 29 and 34 gestational weeks. Rather, ACS could
      increase the risk of RDS. In cases of SGA neonate delivered between 32 and 34
      complete gestational weeks, the risk of hypoglycemia was significantly increased.
      The use of ACS in women with preterm SGA infants needs to be evaluated further,
      especially after 32 weeks' gestation.

PMID- 29372145
TI  - Effects of corticotropin-releasing hormone on the expression of adenosine
      triphosphate-sensitive potassium channels (Kir6.1/SUR2B) in human term pregnant
      myometrium.
AB  - Objective: Corticotropin-releasing hormone (CRH) is a crucial regulator of human
      pregnancy and parturition. Adenosine triphosphate (ATP)-sensitive potassium
      (KATP) channels are important for regulating myometrial quiescence during
      pregnancy. We investigated regulatory effects of different concentrations of CRH
      on KATP channel expression in human myometrial smooth muscle cells (HSMCs) in in
      vitro conditions. Methods: After treating HSMCs with different concentrations of
      CRH (1, 10, 102, 103, 104 pmol/L), mRNA and protein expression of KATP channel
      subunits (Kir6.1 and SUR2B) was analyzed by reverse transcription-polymerase
      chain reaction and western blot. We investigated which CRH receptor was involved
      in the reaction and measured the effects of CRH on intracellular Ca2+
      concentration when oxytocin was administered in HSMCs using Fluo-8 AM ester.
      Results: When HSMCs were treated with low (1 pmol/L) and high (103, 104 pmol/L)
      CRH concentrations, KATP channel expression significantly increased and
      decreased, respectively. SUR2B mRNA expression at low and high CRH concentrations
      was significantly antagonized by antalarmin (CRH receptor-1 antagonist) and
      astressin 2b (CRH receptor-2 antagonist), respectively; however, Kir6.1 mRNA
      expression was not affected. After oxytocin treatment, the intracellular Ca2+
      concentration in CRH-treated HSMCs was significantly lowered in low concentration
      of CRH (1 pmol/L), but not in high concentration of CRH (103 pmol/L), compared to
      control. Conclusion: Our data demonstrated the regulatory effect was different
      when HSMCs were treated with low (early pregnancy-like) and high (labor-like) CRH
      concentrations and the KATP channel expression showed significant increase and
      decrease. This could cause inhibition and activation, respectively, of uterine
      muscle contraction, demonstrating opposite dual actions of CRH.

PMID- 29372146
TI  - History-indicated cerclage: the association between previous preterm history and
      cerclage outcome.
AB  - Objective: Our hospital's policy is to perform history-indicated cerclage (HIC)
      for pregnant patients with 1 or more second-trimester pregnancy losses. Recently,
      the American College of Obstetricians and Gynecologists (ACOG) guideline
      regarding indications for HIC was changed from 3 or more previous second
      trimester fetal losses to one or more. In this study, we aimed to evaluate the
      efficacy of the revised guideline and to investigate the association between
      previous preterm history and cerclage outcome. Methods: We conducted a
      retrospective observational study of cases of HIC in singleton pregnancies
      performed at our hospital between January 2007 and June 2016. We compared the
      perioperative complications and incidences of preterm delivery in patients with
      one previous second-trimester pregnancy loss against those in patients with >=2
      losses. Results: The incidence of preterm delivery (<32 weeks) was significantly
      lower in patients with one previous second-trimester pregnancy loss than in those
      with >=2 losses (15/194 [8%] vs. 28/205 [14%]). In the 1 loss and >=2 losses
      groups, the rates of preterm premature rupture of membranes (PPROM) were 7% and
      8%, the rates of PPROM at <32 weeks 2.1% and 3.4%, and the ratios of neonatal
      intensive care unit admission 10% and 17%, respectively. Conclusion: Comparison
      of HIC in one previous second-trimester pregnancy loss group with HIC in the 2 or
      more previous second-trimester pregnancy loss group found no difference in
      pregnancy outcome. This finding supports the amended ACOG guideline for HIC
      indications. Based on our results, we also propose development of a new protocol
      for HIC-related complications.

PMID- 29372147
TI  - Evaluation of nausea and vomiting in pregnancy using the Pregnancy-Unique
      Quantification of Emesis and Nausea scale in Korea.
AB  - Objective: Severity of nausea and vomiting of pregnancy (NVP) is associated with
      adverse pregnancy outcomes and poorer quality of life (QOL). The aim of this
      study was to evaluate the severity of NVP and maternal well-being status using
      the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scale in a Korean
      population. Methods: A total of 527 pregnant women who were receiving prenatal
      care at 4 hospitals were asked to participate in the study between January 2015
      and June 2015. The severity of NVP was evaluated by the PUQE scale and maternal
      well-being status was evaluated using the visual analogue scale (VAS).
      Statistical analyses were performed to determine the risk factors associated with
      NVP and the associations between the severity of NVP and QOL. Results: Among the
      472 eligible pregnant women, 381 (80.7%) were suffering from NVP during
      pregnancy. No significant differences (P>0.05) were observed in any of the
      variables between the 2 study groups, with the exception of smoking, alcohol
      consumption, and history of NVP. NVP history was found to be the most powerful
      risk factor (adjusted odds ratio, 11.6; 95% confidence interval, 4.7-28.7). The
      correlation coefficient (r) between the VAS scores of maternal well-being status
      and PUQE severity was -0.25 (r2=0.062; P<0.001). Conclusion: In this study, an
      explicit decline in maternal well-being status was observed according to severity
      of NVP. The PUQE scale may be of help to clinicians, healthcare providers, and
      researchers because of its simplicity and usefulness as a tool for NVP
      evaluation.

PMID- 29372148
TI  - Prevalence of vaginal microorganisms among pregnant women according to trimester
      and association with preterm birth.
AB  - Objective: The aim of this study was to investigate the prevalence of abnormal
      vaginal microorganisms in pregnant women according to trimester, and to determine
      whether the presence of abnormal vaginal colonization is associated with higher
      risk of miscarriage or preterm delivery. Furthermore, we analyzed delivery
      outcomes according to individual microorganism species. Methods: We included
      pregnant women who underwent vaginal culture during routine prenatal check-up
      between January 2011 and June 2016. We compared delivery outcomes according to
      the presence or absence of abnormal vaginal flora grouped by trimester. Results:
      This study included 593 singleton pregnancies. We classified participants into 3
      groups, according to the trimester in which vaginal culture was performed; 1st
      trimester (n=221), 2nd trimester (n=138), and 3rd trimester (n=234). Abnormal
      vaginal colonization rate significantly decreased with advancing trimester of
      pregnancy (21.7% for 1st, 21.0% for 2nd, 14.5% for 3rd; P=0.048). Abnormal
      vaginal colonization detected in the 2nd trimester but not in 1st trimester was
      associated with a significant increase in preterm delivery before 28 weeks of
      gestation (6.9% vs. 0%; P=0.006). Among abnormal vaginal flora isolated in the
      2nd trimester, the presence of Klebsiella pneumonia was identified as significant
      microorganism associated with preterm delivery before 28 weeks of gestation (50%
      vs. 0.7% for K. pneumonia; P=0.029). Conclusion: There is an association between
      abnormal vaginal colonization detected in the 2nd trimester and preterm delivery
      before 28 weeks. K. pneumonia has been identified as the likely causative
      microorganisms.

PMID- 29372149
TI  - Decision-to-delivery interval in emergency cesarean delivery in tertiary care
      hospital in Thailand.
AB  - Objective: To determine the decision-to-delivery interval (DDI) in emergency
      cesarean delivery and associated factors. Methods: A total of 431 pregnant women
      who were indicated for emergency cesarean delivery were included. Clinical
      information and timing of process after decision until delivery and pregnancy
      outcomes were evaluated. Results: Mean age was 30 years, and 59.4% were
      nulliparous. Mean gestational age at delivery was 37.9 weeks. The decision was
      made during normal office hour in 33.2%. Median decision-to-operating room
      interval, decision-to-incision interval, and DDIs were 45, 70, and 82 minutes,
      respectively. Only 3.5% of patients had DDI <=30 minutes, while 52.0% had DDI >75
      minutes. During after office hours, every time interval was significantly shorter
      and 4.9% had DDI <=30 minutes compared to 0.7% in normal office hours (P=0.001).
      Compared to other indications, time intervals were significantly shorter in those
      with non-reassuring fetal heart rate (FHR), and DDI <=30 minutes was achieved in
      18.8% vs. 0.8% (P<0.001). Shortest DDI was observed among those with non
      reassuring FHR during after office hours. Neonatal outcomes were comparable
      between different DDIs. Conclusion: Only 3.5% of emergency cesarean delivery had
      a DDI <=30 minutes (median 82 minutes). Significant shorter time intervals were
      observed in those with non-reassuring FHR during after office hours.

PMID- 29372150
TI  - Total and ionized serum magnesium and calcium levels during magnesium sulfate
      administration for preterm labor.
AB  - Objective: This study aimed to estimate the association between total and ionized
      magnesium, and the changes in serum magnesium and calcium levels in patients with
      preterm labor during magnesium sulfate (MgSO4) administration. Methods: The study
      population included 64 women who were candidates for intravenous MgSO4 treatment
      for preterm labor. Serial blood samples were taken and measured total magnesium
      (T-Mg), ionized magnesium (I-Mg), total calcium (T-Ca), and ionized calcium (I
      Ca) levels every one-week interval (1st, 2nd, 3rd). Results: There was no
      significant difference in T-Mg and I-Mg levels during MgSO4 administration
      (P>0.05). There was no significant difference in T-Ca and I-Ca levels during
      MgSO4 administration (P>0.05). Compared before and after administration of MgSO4,
      T-Mg and I-Mg levels and T-Ca levels were changed allow statistically significant
      (P<0.05). But, there was no significant difference in the I-Ca serum levels
      before and after MgSO4 administration (P=0.495). The I-Mg levels for patients
      with adverse effect were higher than other group but did not reach statistical
      significance (P>0.05). There was significant correlation between levels of I-Mg
      and T-Mg (I-Mg=0.395*T-Mg+0.144, P<0.01). Conclusion: There were no significant
      differences in serum Mg and Ca levels during MgSO4 administration for preterm
      labor. Compared to the before and after administration of MgSO4, only I-Ca levels
      were not substantially changed. There are significant correlations between I-Mg
      and T-Mg levels during administration of MgSO4 and I-Mg level seemed to have more
      correlation with adverse effect than T-Mg.

PMID- 29372151
TI  - Efficacy and side effect of ritodrine and magnesium sulfate in threatened preterm
      labor.
AB  - Objective: In terms of efficacy, several previous studies have shown that the
      success rate in inhibiting preterm labor was not different between magnesium
      sulfate and ritodrine. However, there is a paucity of information regarding the
      efficacy of both medications after consideration of intra-amniotic infection,
      which is one of the most important prognostic factors in patients of threatened
      preterm birth. The objective of this study was to compare the efficacy and safety
      of magnesium sulfate with that of ritodrine in preterm labor. Methods: In this
      retrospective cohort study, we included patients who were admitted and treated
      with either ritodrine or magnesium sulfate with the diagnosis of preterm labor at
      24-33.6 weeks of gestational age between January 2005 to April 2015. Patients
      were divided into 2 groups according to the first-used tocolytics (ritodrine
      group and magnesium sulfate group). We compared the efficacy and prevalence of
      side effect in each group. The efficacy of both tocolytics was evaluated in terms
      of preterm delivery within 48 hours, 7 days, or 37 weeks of gestation and need
      for 2nd line therapy. Results: A total number of 201 patients were enrolled
      including 177 cases in ritodrine group and 24 cases in magnesium sulfate group.
      The efficacy of both tocolytics (preterm delivery within 48 hours, 7 days, or 37
      weeks of gestation and need for 2nd line therapy) was not different between the 2
      groups of cases. In multivariate analysis, gestational age at treatment, twin
      gestation, intra-amniotic infection and maternal C-reactive protein (CRP) was
      associated with treatment failure (preterm delivery within 48 hours), but the
      type of tocolytics was not significantly associated with treatment failure. The
      type of side effect was different in the 2 groups, but the frequency of total
      adverse effect, need for discontinuation of therapy because of maternal adverse
      effect, and severe adverse effect were not different between the two groups of
      cases. Conclusion: The efficacy and safety of magnesium sulfate was similar to
      ritodrine, and can be a substitute tocolytics. Additionally, failure of tocolytic
      therapy was determined by gestational age at treatment, twin gestation, intra
      amniotic infection, and maternal CRP, not by the type of tocolytics.

PMID- 29372152
TI  - Effects of estradiol on HIF-1alpha expression and trophoblast differentiation in
      first trimester villous explant cultures.
AB  - Objective: The purpose of this study was to investigate the effects of estradiol
      on the expression of hypoxia-inducible factor (HIF)-1alpha and the
      differentiation of trophoblasts in human first trimester villous explant
      cultures. Methods: Villous explant cultures were established from first trimester
      human placentas (6-8 weeks of gestation, n=3). Normal villous tissues were
      explanted on Matrigel and incubated under 3% O2 tension for 5 days. To evaluate
      the effects of estradiol on the villous explant cultures, 1 ng/mL of estradiol
      was added to the culture medium. The morphological integrities and viabilities of
      the villous explants were monitored. Immunohistochemistry for alpha5 and alpha1
      integrin was performed to assess differentiation of extravillous trophoblasts
      (EVTs). Expression of HIF-1alpha in villous explant cultures was evaluated by
      western blotting and densitometry. Results: EVTs emerging from first trimester
      villous explant cultures formed outgrowths of cells from the distal ends and
      invaded the surrounding Matrigel. Exposure of villous explants to estradiol
      resulted in the decreased outgrowth of cells from the distal end and decreased
      expression of alpha5 integrin. However, estradiol treatment increased the
      invasion of villous explants into the surrounding Matrigel, concomitant with the
      increased expression of alpha1 integrin, indicating differentiation of EVTs into
      more invasive EVTs. On western blots, the expression of HIF-1alpha decreased
      significantly after treatment with estradiol under 3% O2 tension. Conclusion: Our
      findings suggest that estradiol may downregulate expression of HIF-1alpha in
      placenta, which in turn promote trophoblast differentiation into invasive
      phenotype.

PMID- 29372153
TI  - Cosmetic outcomes of cesarean section scar; subcuticular suture versus
      intradermal buried suture.
AB  - Objective: The objective of the study was to compare cosmetic outcomes and
      overall satisfaction rate of cesarean section scar between conventional
      subcuticular suture and intradermal buried vertical mattress. Methods: Patients
      were enrolled to the study by chart review. A scar assessment was obtained
      retrospectively through a telephone survey. The patient component of the patient
      and observer scar assessment scale (POSAS) was utilized along with the overall
      satisfaction of the patient regarding their cesarean section scar and their
      willingness to choose the same skin closure technique when anticipating their
      next cesarean section. Results: A total of 303 cases of cesarean section was
      recruited, 102 finished telephone surveys were calculated for the analyses.
      Subcuticular suture was regarded as control group (n=52) and intradermal buried
      suture as test group (n=50). The PSAS score of the test group (mean, 21.8) was
      lower than that of the control group (mean, 28), with a statistical significance
      (P=0.02). Overall satisfaction rate did not differ between the two groups. Two
      parameters of the PSAS score and the level of overall satisfaction showed
      significant correlation (Pearson's r, -0.63; P<0.01). Conclusion: We suggested
      the use of intradermal buried vertical mattress as a cosmetically superior skin
      closure method for application in cesarean sections over subcuticular stitch.

PMID- 29372154
TI  - Factors associated with parametrial involvement in patients with stage IB1
      cervical cancer: Who is suitable for less radical surgery?
AB  - Objective: To detect the possible clinicopathologic factors associated with
      parametrial involvement in patients with stage IB1 cervical cancer and to
      identify a cohort of patients who may benefit from less radical surgery. Methods:
      We retrospectively reviewed 120 patients who underwent radical hysterectomy and
      pelvic lymphadenectomy as treatment for stage IB1 cervical cancer. Results:
      Overall, 18 (15.0%) patients had parametrial tumor involvement. Tumor size larger
      than 2 cm, invasion depth greater than 1 cm, presence of lymphovascular space
      involvement (LVSI), corpus involvement, and positive lymph nodes were
      statistically associated with parametrial involvement. Multivariate analysis for
      other factors showed invasion depth >1 cm (P=0.029), and corpus involvement
      (P=0.022) were significantly associated with parametrial involvement. A subgroup
      with tumor size smaller than 2 cm showed no parametrial involvement, regardless
      of invasion depth or presence of LVSI. Conclusion: Tumor size smaller than 2 cm
      showed no parametrial involvement, regardless of invasion depth or presence of
      LVSI. Invasion depth >1 cm and corpus involvement were significantly associated
      with parametrial involvement in multivariate analysis. These finding may suggest
      that tumor size may a strong predictor of parametrial involvement in
      International Federation of Gynecology and Obstetrics stage IB1 cervical cancer,
      which can be used to select a subgroup population for less radical surgery.

PMID- 29372155
TI  - Pre-implantation genetic diagnosis and pre-implantation genetic screening: two
      years experience at a single center.
AB  - Objective: Indications for preimplantation genetic diagnosis
      (PGD)/preimplantation genetic screening (PGS) cycles and clinical outcomes were
      evaluated at CHA Gangnam Medical Center. Methods: This is retrospective cohort
      study. All patients (n=336) who went through in vitro fertilization (IVF)-PGD/PGS
      cycles (n=486) between January 2014 and December 2015 were included in Fertility
      Center of CHA Gangnam Medical Center. Patients underwent IVF-PGD/PGS with 24
      chromosome screening. Patients with euploid embryos had transfer of one or 2
      embryos in a fresh cycle with any subsequent frozen embryo transfer (ET) cycle.
      Compared implantation, clinical pregnancy, ongoing pregnancy, and early abortion
      rates were the main outcome measures. Results: The most common indication for
      PGD/PGS was recurrent spontaneous abortion (n=160). The chromosome rearrangement
      cases (n=116) included 24 Robertsonian translocations, 60 reciprocal
      translocations, 3 inversions, 2 deletions, 4 additions, and 23 mosaicisms. PGS
      cases rather than the PGD cases showed higher implantation rates (26.4% vs.
      20.3%), ongoing pregnancy rates (19.5% vs. 16.4%), and clinical pregnancy rates
      (28.6% vs. 23.3%). Implantation rates (30.3% vs. 23.7%), clinical pregnancy rates
      (39.2% vs. 25.2%), and ongoing pregnancy rates (25.7% vs. 17.5%) were significant
      higher in the blastocyst evaluation group than cleavage stage evaluation group.
      Conclusion: This was the largest study of PGD/PGS for 2 years at a single center
      in Korea. The pregnancy outcomes of PGD cases are slightly lower than PGS cases.
      It was confirmed again that success rate of PGD/PGS is higher if biopsy was done
      at blastocyst than cleavage stage.

PMID- 29372156
TI  - Efficacy of luteal estrogen administration and an early follicular Gonadotropin
      releasing hormone antagonist priming protocol in poor responders undergoing in
      vitro fertilization.
AB  - Objectives: We investigated whether luteal estrogen administration and an early
      follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol
      improves clinical outcomes in poor responders to controlled ovarian stimulation
      for in vitro fertilization (IVF)-embryo transfer, and identified underlying
      mechanisms. Methods: This restrospective study consisted of 65 poor responders
      who underwent the E/G-ant priming protocol. Sixty-four other poor responders
      undergoing conventional protocols without pretreatment were included as the
      control group. Clinical outcomes were compared between 2 groups. Results: The E/G
      ant priming protocol group exhibited improvements over the control group in terms
      of the number of retrieved oocytes (3.58+/-2.24 vs. 1.70+/-1.45; P=0.000), mature
      oocytes (2.68+/-2.11 vs. 1.65+/-1.23; P=0.000), fertilized oocytes (2.25+/-1.74
      vs. 1.32+/-1.26; P=0.001), good embryos (1.62+/-0.91 vs. 1.14+/-0.90, P=0.021).
      Day 3 follicle-stimulating hormone (FSH; 8.40+/-4.84 vs. 16.39+/-13.56; P=0.000)
      and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were
      significantly higher in the control group than in the E/G-ant priming group. The
      overall rate of positive human chorionic gonadotropin tests was higher in the E/G
      ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also,
      clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births
      (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group
      than in the control group. Conclusion: The E/G-ant priming protocol would lead to
      promising results in poor responders to IVF by suppressing endogenous FSH and by
      preventing premature luteinization.

PMID- 29372158
TI  - Acculturation and body mass index among marriage-based immigrant Vietnamese women
      in Korea.
AB  - Objective: This study aimed to analyze the association of socioeconomic factors,
      acculturation, and body mass index (BMI) as the first large prospective cohort
      study to determine the state of health of Vietnamese-born migrant women residing
      in Korea. Methods: Participants were Vietnamese marriage-based immigrant women
      living in Korea. Data (n=1,066) was collected during both periods of baseline
      (2006-2011) and follow-up (2012-2014) in 34 cities in Korea. Results: The results
      show that acculturation stress is relatively low among participants. Current BMI
      showed a significant difference according to the current age, monthly family
      income, and psychophysical stress. Depending on age, education level, monthly
      family income, we identified a significant difference in the annual BMI change.
      In correlation analysis, current BMI was significantly associated with age at
      arrival, reading and writing in Korean language adaptation, and psychophysical
      stress. Annual BMI change was significantly associated with age at arrival and
      years since immigration. Conclusion: Our analysis revealed that acculturation
      measured by Acculturative Stress Scale for International Students had no
      association with current BMI or annual BMI change, but had an association with
      several socioeconomic statuses. This study had the advantage that subjects had a
      homogenous background of marriage-based immigrant women, so we could see the
      association of BMI and acculturation, without considering cofounding factors.

PMID- 29372157
TI  - Clinical experience of long-term use of dienogest after surgery for ovarian
      endometrioma.
AB  - Objective: Endometriosis is a common and recurring gynecologic disease which have
      afflicting females of reproductive age. We investigated the efficacy of long
      term, post-operative use of dienogest for ovarian endometrioma. Methods: We
      studied 203 patients who had undergone laparoscopic or robotic surgery for
      ovarian endometrioma, and were administrated dienogest 2 mg/day beginning in July
      of 2013, and continuing. We evaluated side effects of dienogest and
      ultrasonography was performed every 6 months to detect potential recurrence of
      endometrioma (2 cm) in these post-surgical patients. Results: The follow-up
      observation periods were 30.2+/-20.9 months from surgery. The mean age was 34.1+/
      7.2 years old. The mean diameter of pre-operative endometrioma was 5.6+/-3.0 cm2.
      One hundred eighty-two (89.7%) women received dienogest continuously for 12.0+/
      7.1 months. Of the subjects, 21 (10.3%) patients discontinued dienogest at 2.4+/
      1.0 months. The most common side effect when dienogest was discontinued was
      abnormal uterine bleeding. The occurrence rate of vaginal bleeding was 15.8%, a
      number which did not differ significantly in patients with/without post-operative
      gonadotropin releasing hormone agonist administration. The other side effects
      were gastrointestinal trouble including constipation, acne, headache, depression,
      hot flush, weight gain, and edema. However, no serious adverse events or side
      effects were documented and recurrent endometriomas were diagnosed in 3 patients
      (1.5%). Conclusion: The data indicates that dienogest was both tolerable and safe
      for long-term use as prophylaxis in an effort to obviate the recurrence of
      ovarian endometrioma post-operatively, as well as potential need for surgical re
      intervention.

PMID- 29372159
TI  - The expression of Mullerian inhibiting substance/anti-Mullerian hormone type II
      receptor in myoma and adenomyosis.
AB  - Objective: We compared the expression levels of Mullerian inhibiting substance
      (MIS)/anti-Mullerian hormone type II receptor (AMHRII) in uterine myoma and
      adenomyosis to evaluate the possibility of using MIS/anti-Mullerian hormone (AMH)
      as a biological regulator or therapeutic agent in patients with uterine leiomyoma
      and adenomyosis. Methods: We studied normal uterine myometrium, leiomyoma,
      endometrial tissue, and adenomyosis from 57 patients who underwent hysterectomy
      for uterine leiomyoma (22 cases) or adenomyosis (28 cases) and myomectomy for
      uterine myoma (7 cases). Immunohistochemical staining was used to confirm the
      MIS/AMHRII protein expression level in each tissue. Reverse transcription
      polymerase chain reaction was performed to quantify MIS/AMHRII mRNA expression.
      Results: The MIS/AMHRII protein was more strongly expressed in uterine myoma
      (frequency of MIS/AMHRII expressing cells: 51.95%+/-13.96%) and adenomyosis
      (64.65%+/-4.85%) tissues than that in the normal uterine myometrium (3.15%+/
      1.69%) and endometrium (31.10%+/-7.19%). In the quantitative analysis of
      MIS/AMHRII mRNA expression, MIS/AMHRII mRNA expression levels in uterine myoma
      (mean density: 4.51+/-0.26) and adenomyosis (6.84+/-0.20) tissues were higher
      than that in normal uterine myometrial tissue (0.08+/-0.09) and endometrial
      tissue (1.63+/-0.06). Conclusion: This study demonstrated that MIS/AMHRII was
      highly and strongly expressed on uterine myoma and adenomyosis. Our data suggest
      that MIS/AMH may be evaluated as a biological modulator or therapeutic agent on
      MIS/AMHRII expressing uterine myoma and adenomyosis.

PMID- 29372160
TI  - Is robot-assisted laparoscopic myomectomy limited in multiple myomas?: a
      feasibility for ten or more myomas.
AB  - Objective: To evaluate the feasibility of robot-assisted laparoscopic myomectomy
      in multiple myomas over 10. Methods: A retrospective study was conducted for 662
      patients who underwent robot-assisted laparoscopic myomectomy and open myomectomy
      by a single operator in a tertiary university hospital. Results: A total of 30
      women underwent removal of 10 or more uterine myomas by robotics and 13 patients
      were selected for this study. The average number of myomas removed was 13.7
      (range 10-20). The maximum diameter of the myomas was 6.8 cm (range 5.0-10.0 cm).
      The sum of the diameters of each myoma was 34.7 cm (range 20.0-54.5 cm) and the
      mass of resected myomas for each case was 229.1 g (range 106.8-437.9 g). In no
      case was the robotic procedure converted into conventional laparoscopy or
      laparotomy, and all patients recovered without any major complications. In
      comparison with 13 cases of open myomectomy during the same period, robotic
      surgery took longer time than open surgery (360.5 vs. 183.8 minutes; P=0.001) but
      had shorter postoperative hospital days after surgery (mean 2.5 vs. 3.5 days;
      P=0.003). Conclusion: Robot-assisted laparoscopic myomectomy could be an
      alternative to laparotomic myomectomy for numerous myomas over 10 in number.

PMID- 29372161
TI  - Menstrual characteristics in Korean women with endometriosis: a pilot study.
AB  - Objective: This study aimed to determine whether the menstrual characteristics
      are different in Korean women with or without ovarian endometrioma. Methods: We
      selected 95 premenopausal women aged below 39 years who underwent laparoscopic
      surgery for ovarian endometrioma (n=46) or other benign ovarian tumors (n=49)
      between April 2016 and February 2017. We excluded those with uterine diseases
      that could potentially affect the menstrual characteristics and those on
      anticoagulants or hormonal medication. At admission, menstrual characteristics
      such as cycle length, cycle regularity, and menstrual duration, were collected.
      In addition, amount of menstrual bleeding and severity of dysmenorrhea were
      recorded using a pictorial blood loss assessment chart (PBAC) and visual analogue
      scale, respectively. Results: Age and parity were similar in both women with
      ovarian endometrioma and women with other benign ovarian tumors. Body mass index
      (BMI) was significantly lower (median, 20.9 vs. 22.1 kg/m2; P=0.031) in women
      with ovarian endometrioma. The amount of menstrual bleeding (median PBAC score,
      183 vs. 165), menstrual duration (median, 6 vs. 6 days), and cycle length in
      women with regular cycle (median, 29.0 vs. 29.2 days) were not different between
      the 2 groups. Pain score was significantly higher (median, 4 vs. 3; P=0.005) in
      women with ovarian endometrioma. Conclusion: We found that the menstrual
      characteristics between women with ovarian endometrioma and women with other
      benign ovarian tumors were similar. We also observed that low BMI may be one of
      the risk factor for endometriosis.

PMID- 29372162
TI  - Ultrasound-guided local injection of methotrexate and systemic intramuscular
      methotrexate in the treatment of cesarean scar pregnancy.
AB  - Objective: To assess the efficacy and safety of ultrasound-guided
      intragestational injection of methotrexate (MTX) and systemic intramuscular MTX
      in the management of cesarean scar pregnancies. Methods: This was a retrospective
      case-control study that included women diagnosed with cesarean scar pregnancy at
      CHA Bundang Medical Center unit between 2009 and 2015. The 26 cases were managed
      with local injection of MTX under ultrasound guidance and 15 cases were treated
      with systemic intramuscular of MTX. After the procedure, serial follow-up
      sonographic examination and serum beta-human chorionic gonadotropin (beta-hCG)
      measurement were performed. Results: The mean initial beta-hCG level was
      20,610.73 mIU/mL and ranged from 263.00-71,316.50 mIU/mL. Mean gestational age
      was 6.3 weeks and ranged from 4.8 to 8.5 weeks. The majority of ectopic cases
      were treated successfully and follow-up beta-hCG level declined abruptly
      following the first dose of MTX. The rate of success of local MTX treatment was
      significantly higher than that of systemic MTX treatment. It was 93.75% vs.
      73.33%, respectively (P<0.05). Conclusion: Ultrasound-guided intragestational
      injection of MTX is an effective method for the management of cesarean scar
      pregnancies and is associated with minimal side effects and high treatment
      success.

PMID- 29372163
TI  - A secondary abdominal pregnancy with unusual placental implantation in the
      fallopian tube: a diagnostic challenge.
AB  - We reported a case of secondary abdominal pregnancy with placental implantation
      into the fallopian tube, diagnosed at 16 weeks, in a woman admitted to the
      emergency room complaining of syncopal attacks. The best approach would be
      termination of the pregnancy, taking into consideration the high risk to the
      mother and the low possibility of alive and healthy birth. We had to perform an
      urgent surgical intervention due to the fact that the patient was in a clinically
      unstable condition, which was related to hemoperitoneum. If placental
      implantation is on abdominal organs or vessel the best approach would be to
      ligate the cord and to leave placenta in situ. Taking into consideration the
      place of placental implant, the removal of the fallopian tube with the placenta
      was the safest approach in this case. The best and most acceptable form of
      treatment would be individualized in case of rare form of ectopic pregnancy.

PMID- 29372164
TI  - Prenatal diagnosis of isolated coronary arteriovenous fistula.
AB  - Coronary arteriovenous fistula (CAVF) is a rare condition defined as an anomalous
      termination of the coronary arteries. The etiology of CAVF is either congenital
      or acquired, and iatrogenic CAVF is most commonly caused by cardiovascular
      surgery or percutaneous intervention. Most of the prenatally diagnosed CAVFs were
      related to complex heart disease, and only few cases of an isolated CAVF have
      been reported to date. We successfully diagnosed an isolated CAVF by fetal
      echocardiography at 25.3 weeks of gestation. Accurate prenatal diagnosis resulted
      in the prompt decision for postnatal surgical correction, and the neonate thrived
      well without any complications.

PMID- 29372165
TI  - Gastric type mucinous endocervical adenocarcinoma of the uterine cervix: very
      rare and interesting case.
AB  - Gastric type mucinous endocervical adenocarcinomas of the uterine cervix (GAC)
      are a newly classified mucinous subtype with morphologically in 2014, WHO. They
      have a much more aggressiveness and show unusual metastatic patterns compared to
      usual type endocervical adenocarcinoma. They tend to present at higher stage and
      even in stage I, they have worse survival. Therefore, differential diagnosis of
      GAC from the usual type of endocervical adenocarcinoma is very important because
      they are related to a significant risk of recurrence and decreased 5-year disease
      specific survival. Besides, GACs are mostly not associated with human
      papillomavirus (HPV) infection and p16 immunohistochemistry is also typically
      negative in GAC that is HPV-unassociated tumor. We report a very rare and
      interesting case of stage IB1 GAC with negative HPV DNA and p16.

PMID- 29372166
TI  - Benign multicystic peritoneal mesothelioma treated with laparoendoscopic single
      site surgery: a case report and review of the literature.
AB  - Benign multicystic peritoneal mesothelioma (BMPM) is rare and difficult to
      diagnose before surgery. We report a case of BMPM incidentally discovered during
      laparoendoscopic single site surgery (LESS) for treatment of a pelvic mass. A 47
      year-old Korean menopaused woman presented to our outpatient clinic with a pelvic
      mass. She had a history of right ovary cystectomy with adhesiolysis at a local
      hospital in 2010. Imaging study of the pelvis revealed a multilocular cystic
      mass. LESS was performed and multiple grapelike clusters of cysts were seen in
      the uterus, cul-de-sac, both adnexa, pelvic wall, and omentum. The appendix was
      grossly free. Frozen biopsy confirmed BMPM. Excision of multiple cyst clusters of
      cysts, resection of the uterus with both adnexa, appendectomy, omentectomy, and
      adhesiolysis were performed with LESS. She is well for 2 years with no
      recurrence. BMPM should be included in the differential diagnosis when small
      multichamber cystic mass is found on ultrasonography.

PMID- 29372168
TI  - Comparison of 3 Knee-Specific Quality-of-Life Instruments for Patients With
      Meniscal Tears.
AB  - Background: Meniscal tears are a common cause of knee pain and disability. The
      objective measurement of the health-related quality of life of patients with
      meniscal tears plays a key role in clinical evaluation and therapeutic decision
      making. Several evaluation tools have been used to measure the effects of
      meniscal tears on knee function and quality of life. However, most of these tools
      are nonspecific for meniscal pathology. Purpose/Hypothesis: The purpose of the
      present study was to compare the capability of 3 commonly used knee assessment
      tools to measure the impact of meniscal tears on knee function and quality of
      life: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC),
      the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario
      Meniscal Evaluation Tool (WOMET). Our null hypothesis was that no difference
      would exist among the 3 assessment tools. Study Design: Cohort study (diagnosis);
      Level of evidence, 2. Methods: A total of 207 consecutive patients (mean +/- SD:
      age, 52.6 +/- 14.3 years) with arthroscopically confirmed meniscal tear were
      included. Preoperatively, 3 knee function and quality-of-life scores were
      obtained: KOOS, WOMAC, and WOMET. The relative outcome scores of the
      questionnaires were compared postoperatively. Results: The sum scores (relative
      scores) were as follows: 234.2 +/- 92.5 (55.7%) for the KOOS, 132.6 +/- 54.3
      (55.5%) for the WOMAC, and 113 +/- 30.8 (71%) for the WOMET. The relative score
      results for the WOMET were significantly higher than those for the WOMAC and the
      KOOS (both P < .01), while no significant difference was found between the WOMAC
      and the KOOS (P = .735). Conclusion: A greater impact on health-related quality
      of life for patients with meniscal tears can be measured with the WOMET when
      compared with the WOMAC and the KOOS. Therefore, using the WOMET can be
      recommended for the evaluation of knee function and quality-of-life impairment of
      patients with meniscal tears.

PMID- 29372167
TI  - A Biomechanical Assessment of Biceps Femoris Repair Techniques.
AB  - Background: Knee injuries encountered in clinical practice can involve avulsions
      of the biceps femoris from the fibula and proximal tibia. Advances in tendon
      repair methods now allow for repairs with increased surface areas using modern
      suture anchor techniques. Despite descriptions of repair techniques, there are no
      biomechanical studies on the biceps femoris for comparison. Purpose/Hypothesis:
      The objective of this controlled laboratory study was to determine the failure
      load of the native biceps femoris distal insertion and to evaluate modern repair
      techniques. Our hypothesis was 2-fold: (1) Suture repairs to the tibia and fibula
      would perform better on tensile testing than repairs to the fibula alone, and (2)
      complex bridge repairs, similar to those frequently used in rotator cuff surgery,
      would perform better on tensile testing than simple repairs. Study Design:
      Controlled laboratory study. Methods: A total of 40 paired, fresh-frozen
      cadaveric specimens were dissected, identifying the biceps femoris and its
      insertion on the proximal tibia and fibula. The native biceps femoris footprint
      was left intact in 8 specimens and tested to failure on a uniaxial materials
      testing machine evaluating tensile properties, while in the other 32 specimens,
      the biceps femoris insertion was dissected using a No. 15 scalpel blade,
      underwent repair, and was then tested to failure on a uniaxial materials testing
      machine evaluating tensile properties. Four repair constructs were evaluated,
      with 8 specimens allocated for each: construct 1 involved a simple repair (ie,
      passing suture through tissue in a running Krackow fashion and tying at the
      anchor site) to the fibula with 2 suture anchors, construct 2 involved a simple
      repair to the fibula and tibia with 3 suture anchors, construct 3 was a fibular
      repair with a tibial suture bridge involving the fibula and tibia and 3 suture
      anchors, construct 4 involved a transosseous repair through the fibula and 1
      suture anchor on the tibia. Analysis of variance was used to evaluate for
      significance of the mean failure load and stiffness between groups. Results: The
      mean (+/-95% CI) failure loads were the following: native biceps femoris, 1280 +/
      247.0 N; simple fibular repair, 173 +/- 84.6 N; simple fibular and tibial
      repair, 176 +/- 48.1 N; fibular repair with tibial suture bridge, 191 +/- 78.5 N;
      and transosseous repair, 327 +/- 66.3 N. The mean stiffness values were the
      following: native, 46 +/- 13.0 N/mm; simple fibular repair, 16 +/- 5.1 N/mm;
      simple fibular and tibial repair, 14 +/- 5.4 N/mm; fibular repair with tibial
      suture bridge, 13 +/- 2.8 N/mm; and transosseous repair, 15 +/- 2.5 N/mm.
      Interconstruct comparison of failure loads revealed no statistical difference
      between constructs utilizing anchors alone. The transosseous repair showed a
      significant difference for the failure load when compared with each anchor repair
      construct (P = .02, .02, and .04 for constructs 1, 2, and 3, respectively).
      Interconstruct comparison of stiffness revealed no statistical difference between
      all constructs (P > .86). None of the repair techniques re-created the failure
      load or stiffness of the native biceps femoris tendon (P = .02). Conclusion: In
      this biomechanical study, no difference was found between the mean failure loads
      of different biceps femoris repair constructs involving suture anchors alone and
      No. 2 braided polyester and ultra-high-molecular-weight polyethylene suture. A
      technique involving transosseous fibular tunnels and 2-mm suture tape illustrated
      a greater mean failure load than repairs relying on suture anchors for fixation.
      Clinical Relevance: Understanding the tensile performance of biceps femoris
      repair constructs aids clinicians with preoperative and intraoperative decisions.
      Current biceps femoris repair techniques do not approximate the native strength
      of the tendon. A transosseous style of repair offers the highest failure load.

PMID- 29372169
TI  - A Comprehensive Evaluation of Factors Affecting Healing, Range of Motion,
      Strength, and Patient-Reported Outcomes After Arthroscopic Rotator Cuff Repair.
AB  - Background: Rotator cuff repair (RCR) leads to improved patient outcomes, which
      may or may not coincide with biological healing of the tendon. Many patient
      factors may play a role in subjective and objective patient outcomes of surgery.
      Purpose: To evaluate the effect of various patient factors and tendon healing on
      range of motion, strength, and functional outcomes after arthroscopic RCR. Study
      Design: Case-control study; Level of evidence, 3. Methods: We reviewed patients
      who underwent arthroscopic RCR. Postoperative endpoints included physical
      examination, repeat magnetic resonance imaging (MRI), and patient-reported
      outcome measures. The Short Form-36 (SF-36) was also completed at enrollment.
      Physical examination included range of motion and strength testing. Preoperative
      tear characteristics and postoperative healing on MRI were recorded. Associations
      between these characteristics and rotator cuff healing were determined.
      Multivariate models investigated factors affecting healing and final outcomes.
      Results: A total of 81 patients had MRI before and a minimum of 1 year after RCR.
      Patient-reported outcomes were available for all patients at mean 2.7 years
      (range, 1-7.7 years) after RCR. Seventy-five patients had physical examination
      data. Patients were less likely to heal if they had tears involving multiple
      tendons (P = .037), tears >2.2 cm (P = .037), tears retracted >2.0 cm (P = .006),
      and tears with cumulative Goutallier grade >=3 (P = .003). Patients who healed
      were stronger on manual muscle testing in forward elevation (P < .001) and
      external rotation (P = .005) and on forward elevation isometric testing (P =
      .033), and they reported better patient-reported outcomes (P <= .01) at final
      follow-up. In multivariate models, tendon healing was associated with less pain
      (P = .019) and better patient-reported outcomes (all P <= .006). Lower SF-36
      mental component summary (MCS) score was associated with increased pain (P =
      .025) and lower final American Shoulder and Elbow Surgeons score (P = .035),
      independent of healing status. Conclusion: Larger, more retracted tears with
      greater fatty infiltration are less likely to heal per MRI. Patients who do not
      heal are weaker and have worse patient-reported outcome measures. Lower SF-36 MCS
      score was associated with poorer patient-reported outcomes independent of tendon
      healing.

PMID- 29372170
TI  - Elbow Dislocation and Subluxation Injuries in the National Collegiate Athletic
      Association, 2009-2010 Through 2013-2014.
AB  - Background: Examination of the incidence of elbow dislocation and subluxation
      injuries in the collegiate athlete population is limited. Purpose: To determine
      the incidence of elbow dislocation and subluxation injuries in the National
      Collegiate Athletic Association (NCAA) and investigate the risk factors involved.
      Study Design: Descriptive epidemiology study. Methods: All elbow subluxation and
      dislocation injuries from the 2009-2010 through 2013-2014 academic years in the
      NCAA Injury Surveillance Program database were extracted. The incidence was
      calculated for different injuries, sports, activity, time in game, competition
      status, and injury characteristics. Such differences were compared by use of risk
      ratios to determine risk factors for injury. Results: The overall incidence of
      elbow instability injuries was 0.04 per 10,000 athlete-exposures (AEs). Elbow
      dislocations were more common, with 553 injuries (82.2%, 0.03/10,000 AEs), while
      elbow subluxations were the minority, with 119 injuries (17.8%, 0.01/10,000 AEs).
      Men's wrestling had the highest incidence of elbow instability (1.08/10,000 AEs),
      more than women's gymnastics (0.74), men's football (0.11), and women's
      volleyball (0.06). All injuries occurred via a contact mechanism, and 99.2% were
      new injuries. Sixty-nine percent of injuries kept athletes sidelined for more
      than 2 weeks. Injuries were 3 times more likely to occur in competition
      (0.08/10,000 AEs) than practice (0.03/10,000 AEs). Injuries sustained during
      competition were 1.4 times more likely to occur early in the match than late.
      Conclusion: Elbow instability injuries are an infrequent but serious source of
      disability for select NCAA athletes, with a number of associated risk factors.
      Athletes sustaining these injuries, along with their coaches and medical
      providers, may benefit from these return-to-play data to best manage expectations
      and outcomes.

PMID- 29372171
TI  - Sleep Facilitates Generalisation of Accent Adaptation to a New Talker.
AB  - Lexically-guided phonetic retuning helps listeners adapt to the phonetic
      "fingerprint" of a talker. Previous findings show that listeners can generalise
      from one accented talker to another accented talker, but only for phonetically
      similar talkers. We tested whether sleep-mediated consolidation promotes
      generalisation across accented talkers who are not phonetically similar. Native
      English participants were trained on a Mandarin-accented talker and tested on
      this talker and an untrained Mandarin talker. Experiment 1 showed adaptation for
      the trained talker and a weak transfer to the untrained talker. In Experiment 2,
      participants were trained and tested either in the morning (Same-Day group) or
      evening (Overnight group), and again after twelve hours. Both groups retained
      talker-specific learning over the 12-hour delay. Importantly, the Overnight group
      showed improvements for the untrained talker, whereas the Same-Day group's
      performance on the untrained talker deteriorated. We suggest that sleep
      facilitated talker generalisation by helping listeners abstract away from
      specific acoustic properties of the trained talker.

PMID- 29372172
TI  - Cryptococcal Disease in the Era of "Test and Treat": Is There Cause for Concern?
AB  - Treatment of cryptococcosis requires deferred initiation of antiretroviral
      therapy (ART). Early ART initiation may be detrimental in the context of
      cryptococcal infection by increasing the risk of immune reconstitution
      inflammatory syndrome (IRIS). We present 3 cases where early ART initiation in
      the presence of unrecognized cryptococcal disease had fatal outcomes.

PMID- 29372173
TI  - Acute Transverse Myelitis Caused by Echovirus 11 in a Pediatric Patient: Case
      Report and Review of the Current Literature.
AB  - A 12-year-old boy presented with acute flaccid weakness of the right upper
      extremity and was found to have acute flaccid myelitis with transverse myelitis
      involving the cervical cord (C1-T1). An interdisciplinary team-based approach was
      undertaken, including input from a generalist, an infectious diseases physician,
      and a pediatric neurologist. Consultation was sought from the Minnesota
      Department of Health to investigate for a potential etiology and source of the
      responsible infection. Evaluation for an infectious etiology demonstrated
      infection with human echovirus 11. The patient recovered with some disability.
      Echovirus 11 is among the more common etiologies of acute flaccid myelitis and
      should be considered in the differential diagnosis of this increasingly
      recognized pediatric infection.

PMID- 29372174
TI  - PRUNE Syndrome Is a New Neurodevelopmental Disorder: Report and Review.
AB  - PRUNE syndrome, or neurodevelopmental disorder with microcephaly, hypotonia, and
      variable brain anomalies (OMIM#617481), is a new rare autosomal recessive
      neurodevelopmental disease that is caused by homozygous or compound heterozygous
      mutation in PRUNE1 on chromosome 1q21. Here, We report on 12-month-old and 30
      month-old girls from 2 unrelated Saudi families with typical presentations of
      PRUNE syndrome. Both patients had severe developmental delay, progressive
      microcephaly, and dysmorphic features. Brain magnetic resonance imaging showed
      slight thinning in the corpus callosum, mild frontal brain atrophy, and delayed
      myelination in one of the patients. Both patients had the same missense mutation
      in PRUNE1 (c.383G>A, p.Arg128Gln), which was not reported before in a homozygous
      state. We compared our patients to previously reported cases. In conclusion, We
      suggest that clinicians consider PRUNE syndrome in any child presenting with
      dysmorphic features, developmental delay, progressive microcephaly, central
      hypotonia, peripheral spasticity, delayed myelination, brain atrophy, and a thin
      corpus callosum.

PMID- 29372175
TI  - Reconstruction of a severe mandibular pathological fracture caused by Langerhans
      cell histiocytosis using a free fibula osteocutaneous flap:a case report.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease in which Langerhans cells,
      which are bone marrow-derived antigen-presenting cells, proliferate in single or
      multiple organs. We successfully treated a patient with unifocal LCH of the
      mandible with malocclusion due to a severe pathological fracture, using
      reconstruction with a vascularised free bone.

PMID- 29372176
TI  - Choice and Constraint in the Negotiation of the Grandparent Role: A Mixed-Methods
      Study.
AB  - Few studies have examined how the allocation and consequences of grandchild care
      vary across different socioeconomic groups. We analyze qualitative data alongside
      data from The Irish Longitudinal Study on Ageing (TILDA), in a convergent mixed
      methods approach. Regression models examined characteristics associated with
      grandchild care, and the relationship between grandchild care and depressive
      symptoms and well-being. Qualitative data shed light on processes and choices
      that explain patterns of grandchild care provision. Tertiary-educated
      grandparents provided less intensive grandchild care compared with primary
      educated. Qualitative data indicated that this pattern stems from early boundary
      drawing among higher educated grandparents while lower socioeconomic groups were
      constrained and less able to say no. Intensive grandchild care was associated
      with more depressive symptoms and lower well-being and was moderated by
      participation in social activities and level of education attainment. The effect
      of grandchild care on well-being of grandparents depends on whether it is
      provided by choice or obligation.

PMID- 29372177
TI  - Characterizing Pediatric Non-Malarial Fever and Identifying the At-Risk Child in
      Rural Malawi.
AB  - Objective. To characterize children with non-malarial fever at risk of
      nonrecovery or worsening in rural Malawi. Methods. This is a subgroup analysis of
      patients <=14 years of age from a prospective cohort study in non-malarial fever
      subjects (temperature >=37.5 degrees C, or fever within 48 hours, and malaria
      negative) in southern Malawi cared for at a mobile clinic during the 2016 dry
      (August to September) or wet (November to December) season. Data collection
      included chart review and questionnaires; 14-day follow-up was conducted. We
      conducted univariate descriptive statistics on cohort characteristics, bivariate
      analyses to examine associations between characteristics and outcomes, and
      multivariate logistic regressions to explore factors associated with nonrecovery.
      Results. A total of 2893 patients were screened, 401 were enrolled, 286 of these
      were children, and 280 children completed follow-up. Eighty-seven percent
      reported symptom resolution, 12.9% reported no improvement, and there were no
      deaths or hospitalizations. No improvement was associated with dry season
      presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P
      = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a
      4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] =
      1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic
      were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI =
      1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion.
      Outcomes were generally excellent in this rural, outpatient pediatric cohort,
      though risk factors for nonrecovery included food insecurity, access to a
      standing clinic, and seasonality. Ideally, this study will inform clinic- and
      policy-level changes aimed at ameliorating the modifiable risk factors in Malawi
      and throughout rural Africa.

PMID- 29372178
TI  - Divide and Control: Comparison of Split and Switch Hybridization Sensors.
AB  - Hybridization probes have been intensively used for nucleic acid analysis in
      medicine, forensics and fundamental research. Instantaneous hybridization probes
      (IHPs) enable signalling immediately after binding to a targeted DNA or RNA
      sequences without the need to isolate the probe-target complex (e. g. by gel
      electrophoresis). The two most common strategies for IHP design are
      conformational switches and split approach. A conformational switch changes its
      conformation and produces signal upon hybridization to a target. Split approach
      uses two (or more) strands that independently or semi independently bind the
      target and produce an output signal only if all components associate. Here, we
      compared the performance of split vs switch designs for deoxyribozyme (Dz)
      hybridization probes under optimal conditions for each of them. The split design
      was represented by binary Dz (BiDz) probes; while catalytic molecular beacon
      (CMB) probes represented the switch design. It was found that BiDz were
      significantly more selective than CMBs in recognition of single base
      substitution. CMBs produced high background signal when operated at 55 degrees C.
      An important advantage of BiDz over CMB is more straightforward design and
      simplicity of assay optimization.

PMID- 29372179
TI  - De Novo Synthesis of Phosphorylated Triblock Copolymers with Pathogen Virulence
      Suppressing Properties That Prevent Infection-Related Mortality.
AB  - Phosphate is a key and universal "cue" in response to which bacteria either
      enhance their virulence when local phosphate is scarce or downregulate it when
      phosphate is adundant. Phosphate becomes depleted in the mammalian gut following
      physiologic stress and serves as a major trigger for colonizing bacteria to
      express virulence. This process cannot be reversed with oral supplementation of
      inorganic phosphate because it is nearly completely absorbed in the proximal
      small intestine. In the present study, we describe the de novo synthesis of
      phosphorylated polyethylene glycol compounds with three defined ABA (hydrophilic/
      phobic/-philic) structures, ABA-PEG10k-Pi10, ABA-PEG16k-Pi14, and ABA-PEG20k
      Pi20, and linear polymer PEG20k-Pi20 absent of the hydrophobic block. The 10k,
      16k, and 20k demonstrate the molecular weights of the poly(ethylene glycol)
      block, and Pi10, Pi14, and Pi20 represent the repeating units of phosphate.
      Polymers were tested for their efficacy against Pseudomonas aeruginosa virulence
      in vitro and in vivo by assessing the expression of the phosphate sensing protein
      PstS, the production of key virulence factor pyocyanin, and Caenorhabditis
      elegans killing assays. Results indicate that all phosphorylated polymers
      suppressed phosphate sensing, virulence expression, and lethality in P.
      aeruginosa. Among all of the phosphorylated polymers, ABA-PEG20k-Pi20 displayed
      the greatest degree of protection against P. aeruginosa. To define the role of
      the hydrophobic core in ABA-PEG20k-Pi20 in the above response, we synthesized
      PEG20k-Pi20 in which the hydrophobic core is absent. Results indicate that the
      hypdrophobic core of ABA-PEG20k-Pi20 is a key structure in its protective effect
      against P. aeruginosa, in part due to its ability to coat the surface of
      bacteria. Taken together, the synthesis of novel polymers with defined structures
      and levels of phosphorylation may elucidate their antivirulence action against
      clinically important and lethal pathogens such as P. aeruginosa.

PMID- 29372180
TI  - An atom interferometer inside a hollow-core photonic crystal fiber.
AB  - Coherent interactions between electromagnetic and matter waves lie at the heart
      of quantum science and technology. However, the diffraction nature of light has
      limited the scalability of many atom-light-based quantum systems. We use the
      optical fields in a hollow-core photonic crystal fiber to spatially split,
      reflect, and recombine a coherent superposition state of free-falling 85Rb atoms
      to realize an inertia-sensitive atom interferometer. The interferometer operates
      over a diffraction-free distance, and the contrasts and phase shifts at different
      distances agree within one standard error. The integration of phase coherent
      photonic and quantum systems here shows great promise to advance the capability
      of atom interferometers in the field of precision measurement and quantum sensing
      with miniature design of apparatus and high efficiency of laser power
      consumption.

PMID- 29372181
TI  - Dynamic traction of lattice-confined platinum atoms into mesoporous carbon matrix
      for hydrogen evolution reaction.
AB  - Constructing atomically dispersed platinum (Pt) electrocatalysts is essential to
      build high-performance and cost-effective electrochemical water-splitting
      systems. We present a novel strategy to realize the traction and stabilization of
      isolated Pt atoms in the nitrogen-containing porous carbon matrix (Pt@PCM). In
      comparison with the commercial Pt/C catalyst (20 weight %), the as-prepared
      Pt@PCM catalyst exhibits significantly boosted mass activity (up to 25 times) for
      hydrogen evolution reaction. Results of extended x-ray absorption fine structure
      investigation and density functional theory calculation suggest that the active
      sites are associated with the lattice-confined Pt centers and the activated
      carbon (C)/nitrogen (N) atoms at the adjacency of the isolated Pt centers. This
      strategy may provide insights into constructing highly efficient single-atom
      catalysts for different energy-related applications.

PMID- 29372182
TI  - Stereochemistry and amyloid inhibition: Asymmetric triplex metallohelices
      enantioselectively bind to Abeta peptide.
AB  - Stereochemistry is vital for pharmaceutical development and can determine drug
      efficacy. Herein, 10 pairs of asymmetric triplex metallohelix enantiomers as a
      library were used to screen inhibitors of amyloid beta (Abeta) aggregation via a
      fluorescent cell-based high-throughput method. Intriguingly, Lambda enantiomers
      show a stronger inhibition effect than Delta enantiomers. In addition, the
      metallohelices with aromatic substituents are more effective than those without,
      revealing that these groups play a key role in the Abeta interaction.
      Fluorescence stopped-flow kinetic studies indicate that binding of the Lambda
      enantiomer to Abeta is much faster than that of the Delta enantiomer.
      Furthermore, studies in enzyme digestion, isothermal titration calorimetry,
      nuclear magnetic resonance, and computational docking demonstrate that the
      enantiomers bind to the central hydrophobic alpha-helical region of Abeta13-23,
      although with different modes for the Lambda and Delta enantiomers. Finally, an
      in vivo study showed that these metallohelices extend the life span of the
      Caenorhabditis elegans CL2006 strain by attenuating Abeta-induced toxicity. Our
      work will shed light on the design and screening of a metal complex as an amyloid
      inhibitor against Alzheimer's disease.

PMID- 29372183
TI  - Verwey-type charge ordering transition in an open-shell p-electron compound.
AB  - The Verwey transition in Fe3O4, a complex structural phase transition concomitant
      with a jump in electrical conductivity by two orders of magnitude, has been a
      benchmark for charge ordering (CO) phenomena in mixed-valence transition metal
      materials. CO is of central importance, because it frequently competes with
      functional properties such as superconductivity or metallic ferromagnetism.
      However, the CO state in Fe3O4 turned out to be complex, and the mechanism of the
      Verwey transition remains controversial. We demonstrate an archetypical Verwey
      type transition in an open p-shell anionic mixed-valence compound using
      complementary diffraction and spectroscopic techniques. In Cs4O6, a phase change
      from a cubic structure with a single crystallographic site for the molecular O2x-
      building units to a tetragonal structure with ordered superoxide O2- and peroxide
      O22- entities is accompanied by a drastic drop in electronic conductivity and
      molecular charge fluctuation rates. The simple CO pattern of molecular units and
      the lack of magnetic order suggest Cs4O6 as a model system for disentangling the
      complex interplay of charge, lattice, orbital, and spin degrees of freedom in
      Verwey-type CO processes.

PMID- 29372184
TI  - Toward biomass-derived renewable plastics: Production of 2,5-furandicarboxylic
      acid from fructose.
AB  - We report a process for converting fructose, at a high concentration (15 weight
      %), to 2,5-furandicarboxylic acid (FDCA), a monomer used in the production of
      polyethylene furanoate, a renewable plastic. In our process, fructose is
      dehydrated to hydroxymethylfurfural (HMF) at high yields (70%) using a gamma
      valerolactone (GVL)/H2O solvent system. HMF is subsequently oxidized to FDCA over
      a Pt/C catalyst with 93% yield. The advantage of our system is the higher
      solubility of FDCA in GVL/H2O, which allows oxidation at high concentrations
      using a heterogeneous catalyst that eliminates the need for a homogeneous base.
      In addition, FDCA can be separated from the GVL/H2O solvent system by
      crystallization to obtain >99% pure FDCA. Our process eliminates the use of
      corrosive acids, because FDCA is an effective catalyst for fructose dehydration,
      leading to improved economic and environmental impact of the process. Our techno
      economic model indicates that the overall process is economically competitive
      with current terephthalic acid processes.

PMID- 29372185
TI  - Case Report: Induced Lactation in a Transgender Woman.
AB  - Objective: Our report describes a case of nonpuerperal induced lactation in a
      transgender woman. Methods: We present the relevant clinical and laboratory
      findings, along with a review of the relevant literature. Results: A 30-year-old
      transgender woman who had been receiving feminizing hormone therapy for the past
      6 years presented to our clinic with the goal of being able to breastfeed her
      adopted infant. After implementing a regimen of domperidone, estradiol,
      progesterone, and breast pumping, she was able to achieve sufficient breast milk
      volume to be the sole source of nourishment for her child for 6 weeks. This case
      illustrates that, in some circumstances, modest but functional lactation can be
      induced in transgender women.

PMID- 29372186
TI  - Newborn follow-up after discharge from a tertiary care hospital in the Western
      Cape region of South Africa: a prospective observational cohort study.
AB  - Background: Current practice in the Western Cape region of South Africa is to
      discharge newborns born in-hospital within 24 h following uncomplicated vaginal
      delivery and two days after caesarean section. Mothers are instructed to bring
      their newborn to a clinic after discharge for a health assessment. We sought to
      determine the rate of newborn follow-up visits and the potential barriers to
      timely follow-up. Methods: Mother-newborn dyads at Tygerberg Hospital in Cape
      Town, South Africa were enrolled from November 2014 to April 2015. Demographic
      data were obtained via questionnaire and medical records. Mothers were contacted
      one week after discharge to determine if they had brought their newborns for a
      follow-up visit, and if not, the barriers to follow-up. Factors associated with
      follow-up were analyzed using logistic regression. Results: Of 972 newborns, 794
      (82%) were seen at a clinic for a follow-up visit within one week of discharge.
      Mothers with a higher education level or whose newborns were less than 37 weeks
      were more likely to follow up. The follow-up rate did not differ based on
      hospital length of stay. Main reported barriers to follow-up included maternal
      illness, lack of money for transportation, and mother felt follow-up was
      unnecessary because newborn was healthy. Conclusions: Nearly 4 in 5 newborns were
      seen at a clinic within one week after hospital discharge, in keeping with local
      practice guidelines. Further research on the outcomes of this population and
      those who fail to follow up is needed to determine the impact of postnatal
      healthcare policy.

PMID- 29372188
TI  - Intraoperative OCT of a Retinal Tack.

PMID- 29372187
TI  - GLOBAL OPIOID EPIDEMIC: DOOMED TO FAIL WITHOUT GENETICALLY BASED PRECISION
      ADDICTION MEDICINE (PAMTM): LESSONS LEARNED FROM AMERICA.
AB  - It is a reality that globally opioid deaths have soared for men and women of all
      social, economic status and age from heroin and fentanyl overdoses. Specifically,
      in the United States, deaths from narcotic overdoses have reached alarming
      metrics since 2010. In fact, the Fentanyl rise is driven by drug dealers who sell
      it as heroin or who use it to lace cocaine or to make illegal counterfeit
      prescription opioids. The President's Commission on the crisis has linked the
      death toll as equivalent to "September 11th every three weeks." In fact, The U.S.
      Centre for Disease Control (CDC) released data showing that opioid-related
      overdoses were up 15% in the first three quarters of 2016 compared to 2015.
      Various governmental organizations including NIDA, are actively seeking
      solutions. However, we argue that unless the scientific community embraces
      genetic addiction risk coupled with potential precision or personalized medicine
      to induce "dopamine homeostasis" it will fail. We now have evidence that a ten
      gene and eleven single nucleotide polymorphism (SNP) panel predicts Addiction
      Severity Index (ASI) for both alcohol and drugs of abuse (e.g., Opioids). In a
      large multi-addiction centre study involving seven diverse treatment programs,
      the genetic addiction risk score (GARSTM) was shown to have a predictive
      relationship with ASI-MV derived alcohol (>= seven alleles), and other drugs (>=
      4 alleles) severity risk scores. In a number of neuroimaging studies, we also
      display that in both animal (bench) and abstinent Chinese severe heroin-dependent
      patients (bedside), BOLD dopamine activation across the brain reward circuitry
      revealed increases in resting state functional connectivity as well volume
      connectivity. It is also known that published nutrigenomic (coupling gene
      polymorphisms with altered KB220z) studies reveal improved clinical outcomes
      related to obesity.

PMID- 29372189
TI  - The OCT Angiography Revolution: Five Emerging Themes.

PMID- 29372190
TI  - Impact of Having a Mentally Disabled Child in the Family on the Oral Health of
      the Healthy Sibling: A Comparative Study.
AB  - PURPOSE: To determine and compare oral health status, knowledge and attitude
      among siblings of mentally disabled with siblings of normal healthy children.
      MATERIALS AND METHODS: 240 study subjects consisting of 120 each of siblings of
      mentally disabled and normal, healthy children (control group) matched for age
      and gender were selected by convenience sampling. Oral health was assessed using
      the WHO-1997 proforma. A pretested questionnaire (30 items) was used for oral
      health knowledge and attitude assessment. Statistical analysis was performed
      using the chi-squared and Mann-Whitney tests. RESULTS: Caries prevalence among
      the siblings of mentally disabled and control group was 82% (mean DMFT 1.68 +/-
      1.18) and 45% (mean DMFT 0.58 +/- 0.72), respectively (p < 0.05). The siblings of
      mentally disabled children also showed good oral health knowledge (mean 7.1 +/-
      1.4) and a positive attitude (p < 0.05). CONCLUSION: Siblings of mentally
      disabled children showed higher caries experience. Knowledge and attitude towards
      oral health was comparatively good among siblings of mentally disabled children.
      They exhibited favourable attitudes and involvement in helping their sibling to
      maintain oral health.

PMID- 29372191
TI  - Use of Casein Amorphous Calcium Phosphate (CPP-ACP) on White-spot Lesions:
      Randomised Clinical Trial.
AB  - PURPOSE: To evaluate the efficacy of casein phosphopeptide-amorphous calcium
      phosphate (CPP-ACP) in the remineralisation of white-spot lesions in 80 anterior
      teeth of children aged 5-13 years enrolled in public schools of the city of
      Botucatu, Sao Paulo, Brazil. MATERIALS AND METHODS: The study sample consisted of
      36 individuals divided into 4 groups: G1. control (placebo paste); G2. fluoride
      gel; G3. CPP-ACP; G4: CPP-ACP + fluoride. Each product was applied twice by a
      calibrated examiner with a week of interval between. Lesions were monitored with
      a DIAGNOdent Pen before the first application, before the second application, and
      1 and 3 months after the first application. To evaluate the lesion intensity, the
      Friedman test was applied, and to compare experimental groups, the Kruskal-Wallis
      test was applied. The analyses were complemented with the Dunn test and the level
      of significance was 5%. RESULTS: At the end of the 90-day trial, the use of CPP
      ACP and fluoride showed comparable results in terms of remineralisation. The best
      white-spot lesion remineralisation was observed when CPP-ACP and fluoride were
      combined. CONCLUSION: The use of CPP-ACP is a good alternative for the
      remineralisation of white-spot lesions. The effect can be improved when this
      product is applied in combination with fluoride.

PMID- 29372192
TI  - Challenge in optoelectronic duplex switches: a red emission large-size single
      crystal and a unidirectional flexible thin film of a hybrid multifunctional
      material.
AB  - Photoelectric dual-function features in bulk crystals or flexible thin films make
      them excellent candidates for important and thriving applications in storage,
      sensing and other information fields. Based on superior advantages such as easy
      and environmentally friendly processing, mechanical flexibility, and ability to
      fabricate films and bulk single crystals; we designed a type of molecular
      material with a photoelectric multi-function switch, [N(NH2CH2CH2)3]2Mn2Cl12
      (compound 1), which exhibits intriguing temperature-dependent dielectric and red
      emission switchable characteristics. This material perfectly explains the
      advantages of molecular materials, while 1 can also be used to fabricate a
      transparent unidirectional film with ultra-flexibility. Moreover, this material
      shows the highest record in signal contrast of ~5 (exceeding all the known
      molecular materials/crystalline switches, revealing its potential to obtain high
      efficiency signal-to-noise ratio), sensitive dielectric bi-stability, and
      excellent switching anti fatigue. These features give it a high application value
      in integrated circuits, optoelectronic seamless integration devices and flexible
      multifunctional devices.

PMID- 29372193
TI  - Photochemical relaxation pathways of S6-methylthioinosine and O6-methylguanosine
      in solution.
AB  - S6-Methylthioinosine and O6-methylguanosine are byproducts resulting from the
      enzymatic reactions of sulfur-substituted prodrugs in cells and from the
      interaction of alkylating agents with cellular DNA, respectively. Their
      photochemistry has not been investigated, and it is currently unknown whether
      light absorption by these byproducts may pose any threat to the cell. In this
      contribution, their photoinduced processes upon absorption of UVB radiation are
      reported using broadband transient absorption spectroscopy. Plausible electronic
      relaxation mechanisms are proposed for both biological molecules, which are
      supported by steady-state absorption and emission measurements, and by singlet
      and triplet vertical excitation energies performed on a large subset of ground
      state optimized conformational isomers in solution. The results are compared to
      the body of knowledge gathered in the scientific literature about the light
      induced processes in the sulfur-substituted and canonical purine monomers. In
      particular, it is shown that S6-methylation decreases the rate to populate the
      lowest-energy triplet state and blueshifts the ground-state absorption spectrum
      compared to those for the sulfur-substituted prodrugs and for the 6-thioguanosine
      metabolite. Similarly, O6-methylation decreases the rate of internal conversion
      to the ground state observed in the guanine monomers by more than 10-fold in
      acetonitrile and 40-fold in aqueous solution, while it redshifts the ground-state
      absorption spectrum. Collectively, this investigation provides relevant new
      insights about the relationship between structural modifications of the purine
      chromophore and the electronic relaxation mechanisms in this important group of
      biological molecules.

PMID- 29372194
TI  - A combined theoretical and experimental investigation of the kinetics and
      dynamics of the O(1D) + D2 reaction at low temperature.
AB  - The O(1D) + H2 reaction is a prototype for simple atom-diatom insertion type
      mechanisms considered to involve deep potential wells. While exact quantum
      mechanical methods can be applied to describe the dynamics, such calculations are
      challenging given the numerous bound quantum states involved. Consequently,
      efforts have been made to develop alternative theoretical strategies to portray
      accurately the reactive process. Here we report an experimental and theoretical
      investigation of the O(1D) + D2 reaction over the 50-296 K range. The
      calculations employ three conceptually different approaches - mean potential
      phase space theory, the statistical quantum mechanical method and ring polymer
      molecular dynamics. The calculated rate constants are in excellent agreement over
      the entire temperature range, exhibiting only weak temperature dependence. The
      agreement between experiment and theory is also very good, with discrepancies
      smaller than 26%. Taken together, the present and previous theoretical results
      validate the hypothesis that long-lived complex formation dominates the reaction
      dynamics at low temperature.

PMID- 29372195
TI  - Microfluidic thread based electroanalytical system for green chromatographic
      separations.
AB  - The use of miniaturized chromatographic systems is an important strategy for
      reducing the consumption of supplies related to separations, allowing the
      development of more sustainable analytical methodologies. However, the high cost
      and complexity in the production of these systems combined with the operational
      difficulties and the need for the use of solvent and sample pretreatment are
      challenges to be overcome in order to make the chromatographic methods greener.
      Here, we report the construction and development of a low cost microfluidic
      system for green and solvent-free chromatographic separations with
      electrochemical detection integrated into cotton threads without the use of any
      mechanical pumping to transport the solutions. The manufacture of the proposed
      system was performed by simple assembly of the components, with the separation of
      the species based on an ion exchange mechanism and detection using gold
      electrodes manufactured directly on the cotton threads. A linear range of 0.025
      5.0 mM was obtained for the effective separation of ascorbic acid (AA) and
      dopamine (DA) with detection limits of 2.89 MUM (for AA) and 4.41 MUM (for DA).
      Each analysis was performed at a low cost (less than 0.01 dollars), and with a
      small volume of waste generated (107.1 MUL). So, the proposed system was
      successfully employed to determine the levels of AA and DA present in the tears
      of healthy volunteers without sample pretreatment, indicating the good analytical
      performance of the system and the possibility of performing greener
      chromatographic separations.

PMID- 29372196
TI  - Fluorescence in sub-10 nm channels with an optical enhancement layer.
AB  - Fluorescence microscopy uniquely enables physical and biological research in
      micro- and nanofluidic systems. However, in channels with depths below 10 nm, the
      limited number of fluorophores results in fluorescence intensity below the
      detection limit of optical microscopes. To overcome this barrier, we applied
      Fabry-Perot interference to enhance fluorescence intensity with a silicon nitride
      layer below the sub-10 nm channel. A silicon nitride layer of suitable thickness
      can selectively enhance both absorption and emission wavelengths, leading to a
      fluorescent signal that is enhanced 20-fold and readily imaged with traditional
      microscopes. To demonstrate this method, we studied the mass transport of a
      binary solution of ethanol and Rhodamin B in 8 nm nanochannels. The large
      molecular size of Rhodamin B (~1.8 nm) relative to the channel depth results in
      both separation and reduced diffusivity, deviating from behavior at larger
      scales. This method extends the widely available suite of fluorescence analysis
      tools and infrastructure to unprecedented sub-10 nm scale with relevance to a
      wide variety of biomolecular interactions.

PMID- 29372197
TI  - A method for the quantitative extraction of gold nanoparticles from human
      bronchoalveolar lavage fluids through a glycerol gradient.
AB  - Bronchoalveolar lavage (BAL) is a diagnostic procedure which samples the cellular
      and non-cellular components of the pulmonary epithelial surface. The inherent
      biological noise of BAL fluids inhibits their direct mineralogical analysis while
      currently available particle retrieval protocols are suspected to impose
      quantitative and qualitative bias on the studied particle load. This study
      presents a simple method for the near-lossless extraction of citrate-capped gold
      nanoparticles from human BAL fluids at sub-ppm levels which enables their
      quantitation and surface characterization. This procedure was modeled according
      to fundamental principles of particle sedimentation and liquid-liquid
      interdiffusion and was evaluated by a battery of analytical techniques. The
      extraction yield of gold nanoparticles ranged from 61 to 86%, with a quantitation
      limit at 0.5 MUg ml-1, as measured by inductively-coupled optical emission
      spectroscopy. Dynamic light scattering could resolve the hydrodynamic size
      distribution of extracted particles which returned significantly different photon
      count rates at various concentrations. Their shape and primary size were easily
      observable by electron microscopy while atomic force microscopy, Auger electron
      spectroscopy and X-ray photoelectron spectroscopy could respectively probe the
      particles' biomolecular corona, detect surface-adsorbed S- and N- species, and
      identify carbon-based covalent bonds.

PMID- 29372198
TI  - Complexation of halide ions to tyrosine: role of non-covalent interactions
      evidenced by IRMPD spectroscopy.
AB  - The binding motifs in the halide adducts with tyrosine ([Tyr + X]-, X = Cl, Br,
      I) have been investigated and compared with the analogues with 3-nitrotyrosine
      (nitroTyr), a biomarker of protein nitration, in a solvent-free environment by
      mass-selected infrared multiple photon dissociation (IRMPD) spectroscopy over two
      IR frequency ranges, namely 950-1950 and 2800-3700 cm-1. Extensive quantum
      chemical calculations at B3LYP, B3LYP-D3 and MP2 levels of theory have been
      performed using the 6-311++G(d,p) basis set to determine the geometry, relative
      energy and vibrational properties of likely isomers and interpret the measured
      spectra. A diagnostic carbonyl stretching band at ~1720 cm-1 from the intact
      carboxylic group characterizes the IRMPD spectra of both [Tyr + X]- and [nitroTyr
      + X]-, revealing that the canonical isomers (maintaining intact amino and
      carboxylic functions) are the prevalent structures. The spectroscopic evidence
      reveals the presence of multiple non-covalent forms. The halide complexes of
      tyrosine conform to a mixture of plane and phenol isomers. The contribution of
      phenol-bound isomers is sensitive to anion size, increasing from chloride to
      iodide, consistent with the decreasing basicity of the halide, with relative
      amounts depending on the relative energies of the respective structures. The
      stability of the most favorable phenol isomer with respect to the reference plane
      geometry is in fact 1.3, -2.1, -6.8 kJ mol-1, for X = Cl, Br, I, respectively.
      The change in pi-acidity by ring nitration also stabilizes anion-pi interactions
      yielding ring isomers for [nitroTyr + X]-, where the anion is placed above the
      face of the aromatic ring.

PMID- 29372199
TI  - Barbiturate end-capped non-fullerene acceptors for organic solar cells: tuning
      acceptor energetics to suppress geminate recombination losses.
AB  - We report the synthesis of two barbiturate end-capped non-fullerene acceptors and
      demonstrate their efficient function in high voltage output organic solar cells.
      The acceptor with the lower LUMO level is shown to exhibit suppressed geminate
      recombination losses, resulting in enhanced photocurrent generation and higher
      overall device efficiency.

PMID- 29372200
TI  - Consequences of realistic embedding for the L2,3 edge XAS of alpha-Fe2O3.
AB  - Cluster models of condensed systems are often used to simulate the core-level
      spectra obtained with X-ray Photoelectron Spectroscopy, XPS, or with X-ray
      Absorption Spectroscopy, XAS, especially for near edge features. The main
      objective of this paper is to examine the dependence of the predicted L2,3 edge
      XAS of alpha-Fe2O3, an example of a high spin ionic crystal, on increasingly
      realistic models of the condensed system. It is shown that an FeO6 cluster model
      possessing the appropriate local site symmetry describes most features of the XAS
      and is a major improvement over the isolated Fe3+ cation. In contrast, replacing
      next nearest neighbor positive point charges with Sc3+, a closed shell cation of
      similar spatial extent to Fe3+, only marginally improves the match to experiment.
      This work suggests that second nearest neighbor effects are negligible. Rather,
      major improvements to the predicted L2,3 edge XAS likely requires additional many
      body effects that go beyond the present study in which the multiplets are
      restricted to arise from angular momentum coupling within a single open shell
      configuration.

PMID- 29372201
TI  - High-precision modular microfluidics by micromilling of interlocking injection
      molded blocks.
AB  - Wider use and adaptation of microfluidics is hindered by the infrastructure,
      knowledge, and time required to build prototype systems, especially when multiple
      fluid operations and measurements are required. As a result, 3D printing of
      microfluidics is attracting interest, yet cannot readily achieve the feature
      size, smoothness, and optical transparency needed for many standard microfluidic
      systems. Herein we present a new approach to the design and construction of high
      precision modular microfluidics, using standard injection-molded blocks that are
      modified using micromilling and assembled via elastically averaged contacts.
      Desktop micromilling achieves channel dimensions as small as 50 MUm depth and 150
      MUm width and adhesive films seal channels to allow internal fluid pressure of
      >400 kPa. Elastically averaged connections between bricks result in a mechanical
      locating repeatability of ~1 MUm, enabling fluid to pass between bricks via an O
      ring seal with >99.9% reliability. We demonstrated and tested block-based systems
      for generating droplets at rates above 9000 min-1 and COV <3%, and integrated
      optical sensors. We also show how blocks can be used to build easily
      reconfigurable interfaces with glass microfluidic devices and imaging hardware.
      Microfluidic bricks fabricated by FDM and SLA 3D printing cannot achieve the
      dimensional quality of molded bricks, yet 3D printing allows customized bricks to
      be integrated with standard LEGOs. Our approach enables a wide variety of modular
      microfluidic units to be built using a widely available, cost-effective platform,
      encouraging use in both research and education.

PMID- 29372202
TI  - High-capacity and long-life lithium storage boosted by pseudocapacitance in three
      dimensional MnO-Cu-CNT/graphene anodes.
AB  - Boosting the lifespan of MnO-based materials for future lithium ion batteries is
      one of the primary challenges due to the intrinsic low ionic conductivity and
      volume expansion during the conversion process. Herein, superior lithium storage
      in a new quaternary MnO-Cu-CNT/graphene composite has been demonstrated, which is
      boosted by pseudocapacitance benefitting from the three-dimensional CNT/graphene
      and nanosized Cu additives. Such architecture offers highly interpenetrated
      porous conductive networks in intimate contact with MnO-Cu grains and abundant
      stress buffer space for effective charge transport upon cycling. The ternary MnO
      Cu-graphene electrode contributes an ever-increasing reversible capacity of 938.3
      mA h g-1 after 800 cycles at 0.8 A g-1. In particular, the quaternary MnO-Cu
      CNT/graphene electrode demonstrates a high specific capacity of 1334 mA h g-1 at
      0.8 A g-1 after 800 cycles and long lifetimes of more than 3500 cycles at 5 A g-1
      with a capacity of 557.9 mA h g-1 and close-to-100% Coulombic efficiency. The
      boosted pseudocapacitive lithium storage together with the simple material
      fabrication method in a MnO-Cu-CNT/graphene hybrid could pave the way for the
      development of high-capacity and long-life energy storage devices.

PMID- 29372203
TI  - Self-standing aptamers by an artificial defect-rich matrix.
AB  - The classical alkanethiol post-passivation can prevent nonspecific binding of
      nucleotide bases onto supporting substrates and help aptamers transition from a
      "lying down" to a "standing up" orientation. However, the surface probes display
      lower binding affinity towards targets than those in bulk solutions due to
      unsatisfied hybridization spaces on the alkanethiol passivated substrate. To
      overcome this challenge, an artificial defect-rich matrix possessing an aptamer
      "self-standing" property created by chemical lift-off lithography (CLL) is
      demonstrated. This approach provided artificial defects on a hydroxyl-terminated
      alkanethiol self-assembled monolayer (SAM), which allowed the insertion of
      thiolated aptamers. The diluted surface molecular environment assisted aptamers
      not only to "self-stand" on the surface, but also to separate from each other,
      providing a suitable surface aptamer density and sufficient space for capturing
      targets. With this approach, the binding affinity of the aptamer towards a target
      was comparable to solution-type probes, showing higher recognition efficiency
      than that in conventional methods.

PMID- 29372204
TI  - Graphene induced electrical percolation enables more efficient charge transport
      at a hybrid organic semiconductor/graphene interface.
AB  - Self-assembly of semiconducting polymer chains during crystallization from a
      liquid or melt dictates to a large degree the electronic properties of the
      resulting solid film. However, it is still unclear how charge transport pathways
      are created during crystallization. Here, we performed complementary in situ
      electrical measurements and synchrotron grazing incidence X-ray diffraction
      (GIXD), during slow cooling from the melt of highly regio-regular poly(3
      hexylthiophene) (P3HT) films deposited on both graphene and on silicon. Two
      different charge transport mechanisms were identified, and were correlated to the
      difference in crystallites' orientations and overall amount of crystallites in
      the films on each surface as molecular self-assembly proceeded. On silicon, a
      weak charge transport was enabled as soon as the first edge-on lamellae formed,
      and further increased with the higher amount of crystallites (predominantly edge
      on and randomly oriented lamellae) during cooling. On graphene however, the
      current remained low until a minimum amount of crystallites was reached, at which
      point interconnection of conducting units (face-on, randomly oriented lamellae
      and tie-chains) formed percolated conducting pathways across the film. This lead
      to a sudden rapid increase in current by ~10 fold, and strongly enhanced charge
      transport, despite a much lower amount of crystallites than on silicon.

PMID- 29372205
TI  - An experimental and theoretical study of adenine adsorption on Au(111).
AB  - A model study of adenine adsorption on the Au(111) surface is reported for
      molecular adlayers prepared by evaporation in vacuum and deposition from
      saturated aqueous solution. The electronic structure and adsorption geometry of
      the molecular films were studied experimentally by X-ray photoelectron
      spectroscopy and near edge X-ray absorption fine structure spectroscopy.
      Adsorption models are proposed for the adlayers arising from the different
      preparation methods. Density functional theory calculations were used to examine
      both parallel and upright adenine adsorption geometries, supply additional
      information on the bond strength, and identify which atom is involved in bonding
      to Au(111). In the case of deposition in vacuum, the adenine molecule is bound
      via van der Waals forces to Au(111) with the molecular plane parallel to the
      surface, consistent with the published scanning tunneling microscopy data on this
      system. The most stable parallel adenine configuration was found to have an
      adsorption energy of ca. -1.1 eV using the optB86b-vdW functional. For adenine
      deposition from aqueous solution, the adlayer is disordered, with molecules in an
      upright geometry, and with an adsorption energy of ca. -1.0 eV, coordinated via
      the imino N3 nitrogen atom. The present study contributes to the substantial
      literature of model studies of adenine on Au(111), complementing the existing
      knowledge with information on electronic structure, bonding geometry and
      adsorption energy of this system.

PMID- 29372206
TI  - Electronic characterization of silicon intercalated chevron graphene nanoribbons
      on Au(111).
AB  - Electronic and thermal properties of chevron-type graphene nanoribbons can be
      widely tuned, making them interesting candidates for electronic and
      thermoelectric applications. Here, we use post-growth silicon intercalation to
      unambiguously access nanoribbons' energy position of their electronic frontier
      states. These are otherwise obscured by substrate effects when investigated
      directly on the growth substrate. In agreement with first-principles calculations
      we find a band gap of 2.4 eV.

PMID- 29372207
TI  - A continuing challenge: N-heterocyclic carbene-catalyzed syntheses of gamma
      butyrolactones.
AB  - Catalytic, stereoselective N-heterocyclic carbene-catalyzed reactions facilitate
      efficient construction of many different heterocyclic compounds, such as the
      enantioenriched 5-membered (gamma) lactones highlighted in this tutorial review.
      Herein, various strategies to enable formal [3+2] type annulations between
      electrophilic carbonyl equivalents and homoenolate nucleophiles for the synthesis
      of gamma-lactones are summarized.

PMID- 29372208
TI  - Protective effect of rosmarinic acid and carnosic acid against streptozotocin
      induced oxidation, glycation, inflammation and microbiota imbalance in diabetic
      rats.
AB  - This study evaluated the protective effects of two rosemary components,
      rosmarinic acid (RA) and carnosic acid (CA), against hypoglycemia,
      hyperlipidemia, oxidative stress and an imbalanced gut microbiota architecture in
      diabetic rats. Treatment with RA and CA (30 mg kg-1) decreased the levels of
      fasting plasma glucose (23.7%, 15.6%), total cholesterol (30.4%, 14.1%) and
      triglyceride (65.7%, 47.8%) at 15 weeks. RA and CA also exhibited an anti
      oxidative and anti-glycative effect by lowering the formation of malondialdehyde
      and advanced glycation end products. In addition, they showed protective effects
      against tissue damage and inflammation in the abdominal aorta, based on
      microscopic observations and the analysis of protein expression. Finally, the
      prebiotic effects of RA and CA on gut microbiota were demonstrated by increasing
      the population of diabetes-resistant bacteria and decreasing the amounts of
      diabetes-sensitive bacteria. Overall, RA showed a stronger protective effect than
      CA in mitigating diabetic symptoms in rats.

PMID- 29372209
TI  - High-throughput sorting of eggs for synchronization of C. elegans in a
      microfluidic spiral chip.
AB  - In this study, we report the use of a high-throughput microfluidic spiral chip to
      screen out eggs from a mixed age nematode population, which can subsequently be
      cultured to a desired developmental stage. For the sorting of a mixture
      containing three different developmental stages, eggs, L1 and L4, we utilized a
      microfluidic spiral chip with a trapezoidal channel to obtain a sorting
      efficiency of above 97% and a sample purity (SP) of above 80% for eggs at
      different flow rates up to 10 mL min-1. The result demonstrated a cost-effective,
      simple, and highly efficient method for synchronizing C. elegans at a high
      throughput (~4200 organisms per min at 6 mL min-1), while eliminating challenges
      such as clogging and non-reusability of membrane-based filtration. Due to its
      simplicity, our method can be easily adopted in the C. elegans research
      community.

PMID- 29372210
TI  - X-ray photochemistry of carbon hydride molecular ions.
AB  - Hydride molecular ions are key ingredients of the interstellar chemistry since
      they are precursors of more complex molecules. In regions located near a soft X
      ray source these ions may resonantly absorb an X-ray photon which triggers a
      complex chain of reactions. In this work, we simulate ab initio the X-ray
      absorption spectrum, Auger decay processes and the subsequent fragmentation
      dynamics of two hydride molecular ions, namely CH2+ and CH3+. We show that these
      ions feature strong X-ray absorption resonances which relax through Auger decay
      within 7 fs. The doubly-charged ions thus formed mostly dissociate into smaller
      ionic carbon fragments: in the case of CH2+, the dominant products are either
      C+/H+/H or CH+/H+. For CH3+, the system breaks primary into CH2+ and H+, which
      provides a new route to form CH2+ near a X-ray source. Furthermore, our
      simulations provide the branching ratios of the final products formed after the X
      ray absorption as well as their kinetic and internal energy distributions. Such
      data can be used in the chemistry models of the interstellar medium.

PMID- 29372211
TI  - Adenine radicals generated in alternating AT duplexes by direct absorption of low
      energy UV radiation.
AB  - There is increasing evidence that the direct absorption of photons with energies
      that are lower than the ionization potential of nucleobases may result in
      oxidative damage to DNA. The present work, which combines nanosecond transient
      absorption spectroscopy and quantum mechanical calculations, studies this process
      in alternating adenine-thymine duplexes (AT)n. We show that the one-photon
      ionization quantum yield of (AT)10 at 266 nm (4.66 eV) is (1.5 +/- 0.3) * 10-3.
      According to our PCM/TD-DFT calculations carried out on model duplexes composed
      of two base pairs, (AT)1 and (TA)1, simultaneous base pairing and stacking does
      not induce important changes in the absorption spectra of the adenine radical
      cation and deprotonated radical. The adenine radicals, thus identified in the
      time-resolved spectra, disappear with a lifetime of 2.5 ms, giving rise to a
      reaction product that absorbs at 350 nm. In parallel, the fingerprint of reaction
      intermediates other than radicals, formed directly from singlet excited states
      and assigned to AT/TA dimers, is detected at shorter wavelengths. PCM/TD-DFT
      calculations are carried out to map the pathways leading to such species and to
      characterize their absorption spectra; we find that, in addition to the path
      leading to the well-known TA* photoproduct, an AT photo-dimerization path may be
      operative in duplexes.

PMID- 29372212
TI  - Enhanced cyclability of Li-O2 batteries with cathodes of Ir and MnO2 supported on
      well-defined TiN arrays.
AB  - The cycling stability of Li-O2 batteries has been impeded by the lack of high
      efficiency, and durable oxygen cathodes for the oxygen-reduction reaction (ORR)
      and the oxygen-evolution reaction (OER). Herein we report a novel TiN nanorod
      array-based cathode, which was firstly prepared by growing a TiN nanorod array on
      carbon paper (CP), and then followed by depositing MnO2 ultrathin sheets or Ir
      nanoparticles on the TiN nanorods to form well-ordered, three-dimensional (3D),
      and free-standing structured cathodes: TiN@MnO2/CP and TiN@Ir/CP. Both cathodes
      exhibited good specific capacity and excellent cycling stability. Their specific
      discharge capacities were up to 2637 and 2530 mA h g-1, respectively. After 200
      cycles for 2000 h at a current density of 100 mA g-1, no obvious decays were
      observed for TiN@MnO2/CP and TiN@Ir/CP cathodes, while significant decreases were
      observed after the 80th and 30th cycles for the Pt/C and TiN/CP cathodes,
      respectively. Such high performance can be ascribed to the 3D array structure
      with enough microspace and high surface area, which facilitated the high
      dispersion of active components and prevented the formation of large/irreversible
      Li2O2.

PMID- 29372220
TI  - Improved quantum efficiency models of CZTSe: GE nanolayer solar cells with a
      linear electric field.
AB  - We fabricated and characterized CZTSe:Ge nanolayer (<10 nm) thin film solar cells
      to quantitatively demonstrate an exact analytical model of quantum efficiency for
      Ge doped CZTSe devices. The linear electric field model is developed with the
      incomplete gamma function of the quantum efficiency as compared to the empirical
      data at forward bias conditions. This model is characterized with a consistent
      set of parameters from a series of measurements and the literature. Using the
      analytical modelling method, the carrier collection profile in the absorber is
      calculated and closely fitted by the developed mathematical expressions to
      identify the carrier dynamics during the quantum efficiency measurement of the
      device. The analytical calculation is compared with the measured quantum
      efficiency data at various bias conditions.

PMID- 29372221
TI  - Remarkable reversal of electrostatic interaction forces on zwitterionic soft
      nanointerfaces in a monovalent aqueous electrolyte: an AFM study at the single
      nanoparticle level.
AB  - Soft (nano)colloids are increasingly used in medical applications due to the
      versatile options they offer in terms of e.g. tunable chemical composition,
      adaptable physical properties and (bio)functionalization perspectives. Obtaining
      a clear understanding of the nature of the interaction forces that such particles
      experience with neighboring charged (bio)surfaces is a mandatory prerequisite to
      draw a comprehensive and mechanistic picture of their stability and reactivity
      and to further optimize their current functionalities. In this study, adopting an
      original strategy for nanoparticle attachment to atomic force microscopy (AFM)
      tips, we demonstrate that the sign of electrostatic forces between carboxylate
      terminated poly(amidoamine) nanodendrimers (~9 nm in diameter) and planar
      cysteamine-coated gold surfaces can be tailored under fixed pH conditions upon
      the sole variation of the monovalent salt concentration in solution. The origin
      of this unconventional electrostatic force reversal is deciphered upon
      confrontation between AFM force measurements and mean-field force evaluation
      performed beyond the Derjaguin approximation by integrating the dendrimer and
      cysteamine electrostatic properties derived independently from electrokinetic
      measurements. It is shown that the electrostatic force reversal (i) originates
      from the zwitterionic character of the nanodendrimer-solution interphase, and
      (ii) becomes operational under the strict condition that the sub-nanometric
      separation distance between peripheral carboxylate groups and intraparticulate
      amines is of the order of the characteristic electric Debye layer thickness. The
      possibility to mediate - via suitable adjustment of monovalent salt content in
      solution - both the magnitude and sign of the electrostatic forces acting on soft
      interfaces with zwitterionic functionality paves the way for the design of
      innovative strategies to control the stability of nanoparticles against
      aggregation, and to modulate their adhesion onto inorganic surfaces or living
      organisms.

PMID- 29372222
TI  - Orthogonal supramolecular protein assembly on patterned bifunctional surfaces.
AB  - We report successful and selective dual protein assembly on patterned
      bifunctional betaCD-Ni(ii)NTA surfaces, using red fluorescent protein variants
      with hexahistidine-tags and teal fluorescent protein variants conjugated with a
      peptide containing three adamantyl groups. We show that dual protein patterns can
      only be assembled, when opposing supramolecular interactions have been optimized
      and nonspecific interactions have been sufficiently suppressed.

PMID- 29372224
TI  - Polyacrylamide "revisited": UCST-type reversible thermoresponsive properties in
      aqueous alcoholic solutions.
AB  - Combining experiments and all-atom molecular dynamics simulations, we study the
      conformational behavior of polyacrylamide (PAM) in aqueous alcohol mixtures over
      a wide range of temperatures. This study shows that even when the microscopic
      interaction is dictated by hydrogen bonding, unlike its counterparts that present
      a lower critical solution temperature (LCST), PAM shows a counterintuitive
      tunable upper critical solution temperature (UCST)-type phase transition in
      water/alcohol mixtures that was not reported before. The phase transition
      temperature was found to be tunable between 4 and 60  degrees C by the type and
      concentration of alcohol in the mixture as well as by the solution concentration
      and molecular weight of the polymer. In addition, molecular dynamics simulations
      confirmed a UCST-like behaviour of the PAM in aqueous alcoholic solutions.
      Additionally, it was observed that the PAM is more swollen in pure alcohol
      solutions than in 80% alcoholic solutions due to theta-like behaviour.
      Additionally, in the globular state, the size of the aggregates was found to
      increase with increasing solvent hydrophobicity and polymer concentration of the
      solutions. Above its phase transition temperature, PAM might be present as
      individual polymer chains in the coil state (<=10 nm). As PAM is a widespread
      polymer in many biomedical applications (gel electrophoresis, etc.), this finding
      could be of high relevance for many more practical applications in high
      performance pharmaceuticals and/or sensors.

PMID- 29372223
TI  - Chronic consumption of a western diet modifies the DNA methylation profile in the
      frontal cortex of mice.
AB  - In our previous work in mice, we have shown that chronic consumption of a Western
      diet (WD; 42% kcal fat, 0.2% total cholesterol and 34% sucrose) is correlated
      with impaired cognitive function. Cognitive decline has also been associated with
      alterations in DNA methylation. Additionally, although there have been many
      studies analyzing the effect of maternal consumption of a WD on DNA methylation
      in the offspring, few studies have analyzed how an individual's consumption of a
      WD can impact his/her DNA methylation. Since the frontal cortex is involved in
      the regulation of cognitive function and is often affected in cases of cognitive
      decline, this study aimed to examine how chronic consumption of a WD affects DNA
      methylation in the frontal cortex of mice. Eight-week-old male mice were fed
      either a control diet (CD) or a WD for 12 weeks, after which time alterations in
      DNA methylation were analyzed. Assessment of global DNA methylation in the
      frontal cortex using dot blot analysis revealed that there was a decrease in
      global DNA methylation in the WD-fed mice compared with the CD-fed mice.
      Bioinformatic analysis identified several networks and pathways containing genes
      displaying differential methylation, particularly those involved in metabolism,
      cell adhesion and cytoskeleton integrity, inflammation and neurological function.
      In conclusion, the results from this study suggest that consumption of a WD
      alters DNA methylation in the frontal cortex of mice and could provide one of the
      mechanisms by which consumption of a WD impairs cognitive function.

PMID- 29372225
TI  - Self-organization in dipolar cube fluids constrained by competing anisotropies.
AB  - For magnetite spherical nanoparticles, the orientation of the dipole moment in
      the crystal does not affect the morphology of either zero field or field induced
      structures. For non-spherical particles however, an interplay between particle
      shape and direction of the magnetic moment can give rise to unusual behaviors, in
      particular when the moment is not aligned along a particle symmetry axis. Here we
      disclose for the first time the unique magnetic properties of hematite cubic
      particles and show the exact orientation of the cubes' dipole moment. Using a
      combination of experiments and computer simulations, we show that dipolar
      hematite cubes self-organize into dipolar chains with morphologies remarkably
      different from those of spheres, and demonstrate that the emergence of these
      structures is driven by competing anisotropic interactions caused by the
      particles' shape anisotropy and their fixed dipole moment. Furthermore, we have
      analytically identified a specific interplay between energy, and entropy at the
      microscopic level and found that an unorthodox entropic contribution mediates the
      organization of particles into the kinked nature of the dipolar chains.

PMID- 29372229
TI  - Protein-mediated anti-adhesion surface against oral bacteria.
AB  - Biomedical materials, such as orthopedic biomaterials, have a great impact on
      improving life quality and self-esteem of human beings. However, the usage of
      fixed appliances during dental treatment often increases the difficulty of oral
      cleaning and enlarges the adhesion opportunity of oral bacteria. Furthermore, the
      existing anti-adhesion coatings, such as polyethylene glycol derivatives and
      zwitterionic polymers, have not been universally accepted in the oral environment
      due to their intrinsic problems. Herein, inspired by the anti-adhesion capability
      of bovine serum albumin, we report a facile protein-based anti-bacterial surface,
      showing excellent anti-adhesion performance toward oral bacteria. This protein
      mediated anti-adhesion strategy may provide a promising clue for developing new
      anti-bacterial biomaterials, such as dental fixed appliances, restorative
      materials and medical mouthwashes.

PMID- 29372230
TI  - Near infrared dye-labelled polymeric micro- and nanomaterials: in vivo imaging
      and evaluation of their local persistence.
AB  - The use of micro- and nanomaterials as carriers of therapeutic molecules can
      enhance the efficiency of treatments while avoiding side effects thanks to the
      development of controlled drug delivery systems. The binding of a dye to a drug
      or to a drug carrier has opened up a wide range of possibilities for an effective
      in vivo optical tracing of drug biodistribution by using non-invasive real-time
      technologies prior to their potential use as therapeutic vectors. Here, we
      describe the fluorescent tagging of polymeric micro- and nanomaterials based on
      poly(lactic-co-glycolic) acid and on the thermoresponsive poly(N
      isopropylacrylamide) with the fluorescent probe IR-820 which was chemically
      modified for its covalent coupling to the materials. The chemical modification of
      the dye and the polymers yielded micro- and nanoparticulated labelled materials
      to be potentially used as drug depots of different therapeutic molecules. In
      vitro biological studies revealed their reduced cytotoxicity. A spatiotemporal in
      vivo micro- and nanoparticle tracking allowed the evaluation of the
      biodistribution of materials showing their local persistence and high
      biocompatibility after pathological studies. These results underline the
      suitability of these materials for the local, sustained, not harmful and/or on
      demand drug delivery and the remarkable importance of evaluating the
      biodistribution of materials and tissue persistence for their use as local drug
      depots.

PMID- 29372231
TI  - Nanospheres with a smectic hydrophobic core and an amorphous PEG hydrophilic
      shell: structural changes and implications for drug delivery.
AB  - The structure of nanospheres with a crystalline core and an amorphous diffuse
      shell was investigated by small-angle neutron scattering (SANS), small-, medium-,
      and wide-angle X-ray scattering (SAXS, MAXS and WAXS), and differential scanning
      calorimetry (DSC). Nanospheres, 28 to 35 nm in diameter, were prepared from a
      triblock copolymer with poly(ethylene glycol) (PEG) hydrophilic end-blocks and
      oligomers of alternating desaminotyrosyl-tyrosine octyl ester (DTO) and suberic
      acid (SA) as the central hydrophobic block. In the lyophilized nanospheres, the
      diffraction patterns show that the PEG shell is ~10 nm in thickness and
      crystalline, and the hydrophobic core is ~10 nm in diameter with a smectic liquid
      crystalline texture. In aqueous dispersions, the hydrated PEG forms an amorphous
      shell, but the crystalline phase in the core persists at concentrations down to 1
      mg ml-1 as evidenced by the sharp MAXS diffraction peak at a d-spacing of 24.4 A
      and a melting endotherm at 40  degrees C. As the dispersion is diluted (<1 mg ml
      1), the core becomes less ordered, and its diameter decreases by 50% even though
      the overall size of the nanosphere remains essentially unchanged. It is likely
      that below a critical concentration, intermixing of hydrophobic segments with the
      PEG segments reduces the size and the crystallinity of the core. At these
      concentrations, the PEG corona forms a eutectic with water. The mechanisms by
      which the concentration of the dispersion influences the structure of the
      nanospheres, and consequently their drug-release characteristics, are discussed.

PMID- 29372232
TI  - Assessing Metronomic Chemotherapy for Progressive Pediatric Solid Malignant
      Tumors.

PMID- 29372233
TI  - Birth Defects Potentially Related to Zika Virus Infection During Pregnancy in the
      United States.

PMID- 29372234
TI  - Comparison of Residual Risk-Based Eligibility vs Tumor Size and Nodal Status for
      Power Estimates in Adjuvant Trials of Breast Cancer Therapies.
AB  - Importance: Many large adjuvant clinical trials end up underpowered because of
      fewer than expected events in the control arm. Ensuring a minimum number of
      events would result in more informative trials. Objective: To calculate
      individualized residual risk estimates using residual risk prediction software
      and assess whether defining eligibility based on a minimum residual risk
      threshold could increase the reliability of clinical trial power calculations
      compared with eligibility criteria based on tumor size and nodal status. Design,
      Setting, and Participants: We estimated residual risk in 443 consecutive patients
      with early-stage breast cancer and assessed clinical trial power as a function of
      residual risk distribution among the accrued patients. We defined residual risk
      as the risk of recurrence that remains despite receipt of standard-of-care
      therapy; this risk is determined by baseline prognostic risk and by the
      improvement from adjuvant therapy. We performed trial simulations to examine how
      the power of a 2-arm, 1:1 randomized clinical trial would change as the residual
      risk distribution of the trial population that met eligibility criteria based on
      tumor size and nodal status changes. We also simulated trials that use a minimum
      residual risk value as eligibility criterion. Main Outcomes and Measures:
      Residual risk; clinical trial power as a function of residual risk distribution
      among the patients. Results: In the 443 patients (mean [SD] age, 56.1 [12.3]
      years; range, 23-89 years), baseline prognostic and residual risks differed
      substantially: 328 (74%) patients had more than 20% baseline risk of recurrence;
      however, after adjustment for treatment effect only 12 (27%) had more than 20%
      residual risk. We assessed residual risk distribution in patient cohorts that met
      tumor size- and nodal status-based eligibility criteria for 3 currently accruing
      randomized adjuvant trials; the median residual risks were 28% (interquartile
      range [IQR], 25%-31%), 22% (IQR, 15%-28%), and 22% (IQR, 15%-28%), respectively,
      indicating that the power of these trials could vary unpredictably. Simulations
      showed that trials that use anatomical risk-based eligibility criteria can become
      underpowered if they accrue patients with low residual risk despite all
      participants meeting eligibility requirements. Using a minimum required residual
      risk threshold as eligibility criterion produced more reliable power
      calculations. Conclusions and Relevance: When tumor size and nodal status are
      used to determine trial eligibility, the residual risk of recurrence can vary
      broadly, leading to unstable power estimates. The success of future adjuvant
      trials could be improved by defining patient eligibility based on a minimal
      residual risk of recurrence, and these trials can achieve a prespecified power
      with smaller sample sizes.

PMID- 29372235
TI  - Computational Fluid Dynamics to Evaluate the Effectiveness of Inferior Turbinate
      Reduction Techniques to Improve Nasal Airflow.
AB  - Importance: Inferior turbinate reduction (ITR) is a commonly performed procedure
      for the treatment of nasal obstruction. Which portion of the inferior turbinates
      should be surgically addressed to improve nasal airflow has yet to be determined.
      Objective: To use computational fluid dynamics (CFD) analysis to evaluate the
      airflow changes after reduction along different portions of the inferior
      turbinate. Design, Setting, and Participants: Computed tomographic scans of 5
      patients were selected. Seven CFD models were created for each patient: 1
      unaltered and 6 various ITRs, including 3 one-third ITRs (anterior, middle, and
      posterior one-third); 2 two-thirds ITRs (anterior and posterior two-thirds); and
      1 full-length ITR model. Total airflow rate and nasal resistance was obtained
      through CFD analysis, and regression analysis was performed on the increased
      nasal volume, locations, and nasal resistance for all 5 patients. Main Outcomes
      and Measures: Total airflow rate and nasal resistance was obtained through CFD
      analysis, and regression analysis was performed on the increased nasal volume,
      locations, and nasal resistance for all 5 patients. Results: Full ITR over the
      whole length was consistently most effective to improve nasal airflow and
      resistance for all 5 patients (2 men and 3 women), adjusted for the volume.
      Regression analysis showed a strong linear (R2>=0.79) relationship between nasal
      volume changes and nasal airflow. However, the most effective location of partial
      turbinate reduction was not consistent among patients. Surprisingly, for some
      patients, posterior ITRs were more effective than anterior ITRs. The site of most
      effective partial ITR differed from 1 side to the other even in the same
      individual. Conclusions and Relevance: The effectiveness of partial ITR and
      target location likely depends on individual patient anatomy. The fact that full
      ITRs were consistently most effective and the linear regression between flow and
      nasal volume changes may indicate that the entire length of the IT has a
      functional impact on nasal airflow and resistance. Level of Evidence: NA.

PMID- 29372237
TI  - Data-Driven Surgical Decision Making in Nasal Airway Surgery.

PMID- 29372236
TI  - Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for
      Prostate Cancer With Adverse Pathological Features.
AB  - Importance: Prostate cancer with adverse pathological features (ie, pT3 and/or
      positive margins) after prostatectomy may be managed with adjuvant radiotherapy
      (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for
      biochemical recurrence. The optimal timing of postoperative radiotherapy is
      unclear. Objective: To compare the clinical outcomes of postoperative ART and
      ESRT administered to patients with prostate cancer with adverse pathological
      features. Design, Setting, and Participants: This multi-institutional, propensity
      score-matched cohort study involved 1566 consecutive patients who underwent
      postprostatectomy ART or ESRT at 10 US academic medical centers between January
      1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to
      account for covariates potentially associated with treatment selection. Data were
      collected from January 1 to September 30, 2016. Data analysis was conducted from
      October 1, 2016, to October 21, 2017. Main Outcomes and Measures: Freedom from
      postirradiation biochemical failure, freedom from distant metastases, and overall
      survival. All outcomes were measured from date of surgery to address lead-time
      bias. Results: Of 1566 patients, 1195 with prostate-specific antigen levels of
      0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen
      levels lower than 0.1 ng/mL received ART. The median age (interquartile range)
      was 60 (55-65) years. After propensity score matching, the median (interquartile
      range) follow-up after surgery was similar between the ESRT and ART groups (73.3
      [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with
      ESRT, was associated with higher freedom from biochemical failure (12-year
      actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size,
      26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%
      90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95%
      CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage,
      nodal irradiation, and postoperative androgen deprivation therapy were favorable
      prognostic features on multivariate analysis for biochemical failure. Sensitivity
      analysis demonstrated that the decreased risk of biochemical failure associated
      with ART remained significant unless more than 56% of patients in the ART group
      were cured by surgery alone. This threshold is greater than the estimated 12-year
      freedom from biochemical failure rate of 33% to 52% after radical prostatectomy
      alone, as determined by a contemporary dynamic nomogram. Conclusions and
      Relevance: Adjuvant RT, compared with ESRT, was associated with reduced
      biochemical recurrence, distant metastases, and death for high-risk patients,
      pending prospective validation. These findings suggest that a greater proportion
      of patients with prostate cancer who have adverse pathological features may
      benefit from postprostatectomy ART rather than surveillance followed by ESRT.

PMID- 29372239
TI  - Hearing Loss Among Older Adults With Heart Failure in the United States: Data
      From the National Health and Nutrition Examination Survey.

PMID- 29372238
TI  - Otolaryngologic Manifestations of Klippel-Feil Syndrome in Children.
AB  - Importance: Children with Klippel-Feil syndrome (KFS), characterized principally
      by abnormal fusion of 2 or more cervical vertebrae, may have many additional
      congenital anomalies. The overall prevalence of otolaryngologic manifestations
      among patients with KFS has not been previously characterized. Objective: To
      define the otolaryngologic diagnoses made and procedures performed in 95 patients
      with KFS, which, to our knowledge, is the largest series of this challenging
      patient population published to date. Design, Setting, and Participants: For this
      retrospective review, all patients with KFS who underwent otolaryngology
      consultation at our institution over a 26-year period (January 1989 to December
      2015) were included. Patients were identified using International Classification
      of Diseases, Ninth Revision (ICD-9) codes and were confirmed through individual
      medical record review. Relevant otolaryngologic diagnoses and procedures were
      extracted using ICD-9 and Current Procedural Terminology codes, respectively.
      Selected demographics included age, sex, number of clinic visits, and number of
      procedures. Main Outcomes and Measures: The primary outcomes were the
      otolaryngologic diagnoses and procedures associated with the KFS patient
      population; the secondary outcome was Cormack-Lehane classification documented
      during airway procedures. Results: Overall, 95 patients with KFS were included in
      this study (55 males [58%] and 40 females [42%]); mean (range) age at time of
      presentation to the otorhinolaryngology clinic was 5.8 (birth-23.0) years. Each
      patient with KFS averaged 8 visits to the otorhinolaryngology office and 5
      otolaryngologic diagnoses. The most common diagnosis was conductive hearing loss
      (n = 49 [52%]), followed by sensorineural hearing loss (n = 38 [40%]), and
      dysphagia (n = 37 [39%]). Sixty-two (65%) patients underwent otolaryngologic
      procedures, with 44 (46%) undergoing multiple procedures. The most common
      procedure was tympanostomy tube placement (n = 36 [38%]), followed by office
      flexible endoscopy (n = 23 [24%]). Twelve of the 20 patients who underwent direct
      laryngoscopy had documented Cormack-Lehane classification; 5 of 12 patients (42%)
      had a compromised view (grade 2, 3, or 4) of the larynx. Three patients required
      tracheotomies at this institution for airway stabilization purposes; each had
      severe upper airway obstruction leading to respiratory failure. Conclusions and
      Relevance: Patients with KFS require consultation for a variety of
      otolaryngologic conditions. Among these, hearing loss is the most common, but
      airway issues related to cervical spine fusion are the most challenging.
      Formulating an appropriate care plan in advance is paramount, even for routine
      otolaryngology procedures.

PMID- 29372240
TI  - Medical Specialties of Clinicians Providing Mechanical Thrombectomy to Patients
      With Acute Ischemic Stroke in the United States.

PMID- 29372241
TI  - Pathogen-Reduced Platelets for the Prevention of Bleeding in People of Any Age.
AB  - Clinical Question: Are pathogen-reduced platelets as effective as standard
      platelets for the prevention of bleeding in people of any age requiring platelet
      transfusions? Bottom Line: In people with cancer who have a low platelet count
      due to their disease or its treatment, pathogen-reduced platelet transfusions
      increase risk of platelet refractoriness and platelet transfusion requirement
      (high-quality evidence) but probably do not effect all-cause mortality, risk of
      clinically significant or severe bleeding, or risk of a serious adverse event
      (moderate-quality evidence). There was insufficient evidence for people with
      other diagnoses.

PMID- 29372242
TI  - Characteristics of Patients Using Patient Portals in Oncology.

PMID- 29372243
TI  - Chronic Inflammation After YAG Capsulotomy.

PMID- 29372244
TI  - Assessing Metronomic Chemotherapy for Progressive Pediatric Solid Malignant
      Tumors-Reply.

PMID- 29372245
TI  - Assessing Metronomic Chemotherapy for Progressive Pediatric Solid Malignant
      Tumors.

PMID- 29372246
TI  - Reducing the Burden of Unilateral Vision Impairment and Blindness in Australia.

PMID- 29372248
TI  - Prevalence of High-Risk Human Papillomavirus in Tonsil Tissue in Healthy Adults
      and Colocalization in Biofilm of Tonsillar Crypts.
AB  - Importance: The pathogenesis of human papillomavirus (HPV)-associated
      oropharyngeal squamous cell carcinoma is currently an important topic of
      elucidation. The presence of latent HPV infection in tonsil tissue of healthy
      adults may provide an explanation for a component of this process and contribute
      to the understanding of HPV-associated squamous cell carcinoma oncogenesis of the
      oropharynx. Objective: To determine the prevalence of oropharyngeal HPV and to
      determine the spatial relationship between the virus and crypt biofilm in tonsil
      tissue. Design, Setting, and Participants: A retrospective, cross-sectional study
      was carried out using samples obtained from tonsils that were archived at a
      university hospital following elective nononcologic tonsillectomy from 2012 to
      2015. Samples consisted of formalin-fixed paraffin embedded samples of tumor-free
      tonsil tissue from 102 adults between the ages of 20 and 39 years. Exposures:
      Human papillomavirus status was assessed by polymerase chain reaction, and high
      risk subtypes 16 and 18 were assessed with quantitative polymerase chain reaction
      assay. Samples that demonstrated presence of HPV were then analyzed by in situ
      hybridization to localize the viral capsid protein. These samples were then
      stained with concanavalin A to establish biofilm presence and morphology. These
      samples were also stained with diamidino-phenylindole (DAPI) to visualize
      location of the virus in relation to cell nuclei. These data were then assembled
      for aggregate analysis to colocalize HPV in the biofilm of the tonsillar crypts.
      Main Outcomes and Measures: Outcome measurements were determined prior to data
      collection and include prevalence of high-risk HPV types 16 and 18 in tonsil
      tissue of otherwise healthy adults, as well as demonstration with
      immunohistochemistry of HPV in tonsillar crypt biofilm. Results: In 102 otherwise
      healthy adults (55 [53.9%] female; age range, 20-39 years), the overall
      prevalence of HPV in tonsils was 4.9% (n = 5); and high-risk type 16 or 18, 3.9%
      (n = 4). In this sample population, in situ hybridization colocalized HPV virus
      to the biofilm of the tonsillar crypts. Conclusions and Relevance: Biofilm is
      present in the tonsillar crypts in a considerable proportion of tonsil tissues
      and may be reproducibly identified. Human papillomavirus is demonstrated to
      colocalize to the crypt biofilm. This has important implications with respect to
      the determination of HPV prevalence rates in the oropharynx. It may also play a
      role in the pathogenesis of HPV-related oropharyngeal carcinoma.

PMID- 29372247
TI  - Association of Intracerebral Hemorrhage Among Patients Taking Non-Vitamin K
      Antagonist vs Vitamin K Antagonist Oral Anticoagulants With In-Hospital
      Mortality.
AB  - Importance: Although non-vitamin K antagonist oral anticoagulants (NOACs) are
      increasingly used to prevent thromboembolic disease, there are limited data on
      NOAC-related intracerebral hemorrhage (ICH). Objective: To assess the association
      between preceding oral anticoagulant use (warfarin, NOACs, and no oral
      anticoagulants [OACs]) and in-hospital mortality among patients with ICH. Design,
      Setting, and Participants: Retrospective cohort study of 141 311 patients with
      ICH admitted from October 2013 to December 2016 to 1662 Get With The Guidelines
      Stroke hospitals. Exposures: Anticoagulation therapy before ICH, defined as any
      use of OACs within 7 days prior to hospital arrival. Main Outcomes and Measures:
      In-hospital mortality. Results: Among 141 311 patients with ICH (mean [SD] age,
      68.3 [15.3] years; 48.1% women), 15 036 (10.6%) were taking warfarin and 4918
      (3.5%) were taking NOACs preceding ICH, and 39 585 (28.0%) and 5783 (4.1%) were
      taking concomitant single and dual antiplatelet agents, respectively. Patients
      with prior use of warfarin or NOACs were older and had higher prevalence of
      atrial fibrillation and prior stroke. Acute ICH stroke severity (measured by the
      National Institutes of Health Stroke Scale) was not significantly different
      across the 3 groups (median, 9 [interquartile range, 2-21] for warfarin, 8 [2-20]
      for NOACs, and 8 [2-19] for no OACs). The unadjusted in-hospital mortality rates
      were 32.6% for warfarin, 26.5% for NOACs, and 22.5% for no OACs. Compared with
      patients without prior use of OACs, the risk of in-hospital mortality was higher
      among patients with prior use of warfarin (adjusted risk difference [ARD], 9.0%
      [97.5% CI, 7.9% to 10.1%]; adjusted odds ratio [AOR], 1.62 [97.5% CI, 1.53 to
      1.71]) and higher among patients with prior use of NOACs (ARD, 3.3% [97.5% CI,
      1.7% to 4.8%]; AOR, 1.21 [97.5% CI, 1.11-1.32]). Compared with patients with
      prior use of warfarin, patients with prior use of NOACs had a lower risk of in
      hospital mortality (ARD, -5.7% [97.5% CI, -7.3% to -4.2%]; AOR, 0.75 [97.5% CI,
      0.69 to 0.81]). The difference in mortality between NOAC-treated patients and
      warfarin-treated patients was numerically greater among patients with prior use
      of dual antiplatelet agents (32.7% vs 47.1%; ARD, -15.0% [95.5% CI, -26.3% to 
      3.8%]; AOR, 0.50 [97.5% CI, 0.29 to 0.86]) than among those taking these agents
      without prior antiplatelet therapy (26.4% vs 31.7%; ARD, -5.0% [97.5% CI, -6.8%
      to -3.2%]; AOR, 0.77 [97.5% CI, 0.70 to 0.85]), although the interaction P value
      (.07) was not statistically significant. Conclusions and Relevance: Among
      patients with ICH, prior use of NOACs or warfarin was associated with higher in
      hospital mortality compared with no OACs. Prior use of NOACs, compared with prior
      use of warfarin, was associated with lower risk of in-hospital mortality.

PMID- 29372249
TI  - Prevalence and Causes of Unilateral Vision Impairment and Unilateral Blindness in
      Australia: The National Eye Health Survey.
AB  - Importance: This study determines the prevalence of unilateral vision impairment
      (VI) and unilateral blindness to assist in policy formulation for eye health care
      services. Objective: To determine the prevalence and causes of unilateral VI and
      unilateral blindness in Australia. Design, Setting, and Participants: This cross
      sectional population-based survey was conducted from March 2015 to April 2016 at
      30 randomly selected sites across all strata of geographic remoteness in
      Australia. A total of 1738 indigenous Australians 40 years or older and 3098
      nonindigenous Australians 50 years or older were included. Main Outcomes and
      Measures: The prevalence and causes of unilateral vision impairment and
      blindness, defined as presenting visual acuity worse than 6/12 and 6/60,
      respectively, in the worse eye, and 6/12 or better in the better eye. Results: Of
      the 1738 indigenous Australians, mean (SD) age was 55.0 (10.0) years, and 1024
      participants (58.9%) were female. Among the 3098 nonindigenous Australians, mean
      (SD) age was 66.6 (9.7) years, and 1661 participants (53.6%) were female. The
      weighted prevalence of unilateral VI in indigenous Australians was 12.5% (95% CI,
      11.0%-14.2%) and the prevalence of unilateral blindness was 2.4% (95% CI, 1.7%
      3.3%), respectively. In nonindigenous Australians, the prevalence of unilateral
      VI was 14.6% (95% CI, 13.1%-16.3%) and unilateral blindness was found in 1.4%
      (95% CI, 1.0%-1.8%). The age-adjusted and sex-adjusted prevalence of unilateral
      vision loss was higher in indigenous Australians than nonindigenous Australians
      (VI: 18.7% vs 14.5%; P = .02; blindness: 2.9% vs 1.3%; P = .02). Risk factors for
      unilateral vision loss included older age (odds ratio [OR], 1.60 for each decade
      of age for indigenous Australians; 95% CI, 1.39-1.86; OR, 1.65 per decade for
      nonindigenous Australians; 95% CI, 1.38-1.96), very remote residence (OR, 1.65;
      95% CI, 1.01-2.74) and self-reported diabetes (OR, 1.52; 95% CI, 1.12-2.07) for
      indigenous Australians, and having not undergone an eye examination in the past 2
      years for nonindigenous Australians (OR, 1.54; 95% CI, 1.04-2.27). Uncorrected
      refractive error and cataract were leading causes of unilateral VI in both
      populations (70%-75%). Corneal pathology (16.7%) and cataract (13.9%) were
      leading causes of unilateral blindness in indigenous Australians, while amblyopia
      (18.8%), trauma (16.7%), and age-related macular degeneration (10.4%) were major
      causes of unilateral blindness in nonindigenous Australians. Conclusions and
      Relevance: Unilateral vision loss is prevalent in indigenous and nonindigenous
      Australians; however, most cases are avoidable. As those with unilateral vision
      loss caused by cataract and posterior segment diseases may be at great risk of
      progressing to bilateral blindness, national blindness prevention programs may
      benefit from prioritizing examination and treatment of those with unilateral
      vision loss.

PMID- 29372251
TI  - Temporal Expression of Genes in Biofilm-Forming Ocular Candida albicans Isolated
      From Patients With Keratitis and Orbital Cellulitis.
AB  - Purpose: To study antibiotic susceptibility and biofilm-forming potential of
      ocular isolates of Candida albicans along with gene expression. Methods: Seven
      clinical isolates of C. albicans (keratitis-6 and orbital cellulitis-1) were
      evaluated. Biofilm formation in one isolate was monitored by scanning electron
      microscopy (SEM) and confocal laser scanning microscopy (CLSM). Expression of 27
      genes (real-time PCR) associated with biofilm formation and virulence was
      compared between biofilm-positive and biofilm-negative ocular C. albicans
      isolates. The temporal expression (4 to 72 hours) of the 27 overexpressed genes
      was also determined. Similar studies were also done with biofilm-positive and
      biofilm-negative nonocular C. albicans. Results: Four of seven ocular C. albicans
      isolates exhibited the potential to form biofilm, one of which was resistant to
      three antifungals, whereas three were susceptible to all. SEM studies indicated
      that biofilm increased from two to three adherent layers of cells at 24 hours to
      multiple layers by 72 hours. CLSM showed that biofilm thickness increased from
      5.2 MUm at 24 hours to 17.98 MUm at 72 hours. Upregulation of 27 genes involved
      in virulence and biofilm formation was observed both in the ocular and nonocular
      C. albicans positive for biofilm formation and compared to the respective non
      biofilm-forming C. albicans. The results also indicated similarity in expression
      of genes between biofilm-forming ocular and nonocular pathogenic C. albicans.
      Temporal expression of the 27 genes (involved in adhesion, initiation,
      maturation, and dispersal stages of biofilm) in the biofilm-positive ocular
      isolate indicated that expression pattern followed four different patterns.
      Conclusions: This is the first study showing similarity in expression of genes in
      biofilm-forming ocular and nonocular isolates of C. albicans, suggesting that
      upregulated genes could serve as a potential target for developing therapeutic
      strategies.

PMID- 29372252
TI  - A Novel Type of Multiterminal Motor Endplate in Human Extraocular Muscles.
AB  - Purpose: To investigate the relation between type of motor endplate,
      acetylcholine receptor (AChR) subunit composition, and fiber types in human
      extraocular muscles (EOMs). Methods: EOM samples collected from subjects aged 34
      to 82 years were serially sectioned and processed for immunohistochemistry, with
      specific antibodies against different myosin heavy chain (MyHC) isoforms,
      neurofilament, synaptophysin, and adult epsilon (epsilon) and fetal gamma (gamma)
      AChR subunits as well as alpha-bungarotoxin. Results: A novel type of motor
      endplate consisting of large, multiterminal en plaque endings was found in human
      EOMs, in addition to the previously well-described single en plaque and multiple
      en grappe endplates. Such novel endplates were abundant but exclusively observed
      in myofibers lacking MyHC slow and fast IIa but containing MyHC extraocular
      (MyHCeom), isoforms. Multiple en grappe endings were found only in myofibers
      containing MyHC slow-tonic isoform and contained fetal gamma AChR subunit. Adult
      epsilon and fetal gamma AChR subunits, alone or combined, were found in the
      multiterminal endplates. Distinct AChR subunits were present in adjacent motor
      endplates of a given myofiber containing MyHCeom. Conclusions: Human EOMs have a
      more complex innervation pattern than previously described, comprising also a
      novel type of multiterminal motor endplate present in myofibers containing
      MyHCeom. The heterogeneity in AChR subunit composition in a given myofiber
      suggests the possible presence of polyneuronal innervation in human EOMs.

PMID- 29372250
TI  - Approach for a Clinically Useful Comprehensive Classification of Vascular and
      Neural Aspects of Diabetic Retinal Disease.
AB  - The Early Treatment Diabetic Retinopathy Study (ETDRS) and other standardized
      classification schemes have laid a foundation for tremendous advances in the
      understanding and management of diabetic retinopathy (DR). However, technological
      advances in optics and image analysis, especially optical coherence tomography
      (OCT), OCT angiography (OCTa), and ultra-widefield imaging, as well as new
      discoveries in diabetic retinal neuropathy (DRN), are exposing the limitations of
      ETDRS and other classification systems to completely characterize retinal changes
      in diabetes, which we term diabetic retinal disease (DRD). While it may be most
      straightforward to add axes to existing classification schemes, as diabetic
      macular edema (DME) was added as an axis to earlier DR classifications, doing so
      may make these classifications increasingly complicated and thus clinically
      intractable. Therefore, we propose future research efforts to develop a new,
      comprehensive, and clinically useful classification system that will identify
      multimodal biomarkers to reflect the complex pathophysiology of DRD and
      accelerate the development of therapies to prevent vision-threatening DRD.

PMID- 29372253
TI  - Outer Retinal Dysfunction in the Absence of Structural Abnormalities in Multiple
      Sclerosis.
AB  - Purpose: Recent evidence suggests structural changes distal to the inner retina
      in multiple sclerosis (MS) patients. The functional correlates of these proposed
      structural abnormalities remain unclear. We investigated outer retinal function
      and structure in MS patients, and quantified to what extent outer retinal
      structure influenced function in these patients. Methods: Outer retinal function
      was assessed using the full-field and multifocal electroretinogram (ERG/MF-ERG),
      whereas retinal structure was assessed using spectral-domain optical coherence
      tomography (OCT). Results were compared with preexisting normative data. The
      relationships between electrophysiology parameters and the OCT values
      corresponding to the proposed cellular origins of the ERG and MF-ERG were
      analyzed. Results: Most electrophysiological responses were delayed in MS
      patients, independently of optic neuritis (ON). Inner retinal thickness and
      volumes were reduced, and inner nuclear layer volume marginally increased, in
      eyes with previous ON; all other OCT parameters were normal. OCT results
      correlated with ERG amplitudes, but not with ERG peak times or any MF-ERG
      parameters. Conclusions: We recorded outer retinal dysfunction without detectable
      abnormalities of the corresponding retinal layers in MS patients, not ascribable
      to retrograde degeneration following ON. The findings complement a growing body
      of literature reporting primary retinal abnormalities distal to the ganglion cell
      inner plexiform layer complex in MS patients, with our data suggesting that this
      may be a more widespread phenomenon than previously thought. ERG may be of more
      utility in detecting retinal dysfunction in MS patients than MF-ERG. Analysis of
      peak times, rather than response amplitudes, is recommended.

PMID- 29372254
TI  - A Novel C-Terminal Mutation in Gsdma3 (C+/H-) Leads to Alopecia and Corneal
      Inflammatory Response in Mice.
AB  - Purpose: Mutations in the gene encoding Gasdermin A3 (Gsdma3) have been described
      to cause severe skin phenotypes, including loss of sebaceous glands and alopecia,
      in mice. We discovered a novel C-terminal mutation in Gsdma3 in a new mouse line
      and characterized a less frequently reported corneal phenotype, likely caused by
      degeneration of Meibomian glands of the inner eyelid. Methods: We used histologic
      methods to evaluate the effects of the C+/H- mutation on sebaceous gland and skin
      morphology as well as Meibomian glands of the inner eyelid and corneal tissue.
      Chromosomal aberrations were excluded by karyogram analyses. The mutation was
      identified by Sanger sequencing of candidate genes. Results: Analyses of skin
      samples from affected mice confirmed the frequently reported phenotypes
      associated with mutations in Gsdma3: Degeneration of sebaceous glands and
      complete loss of pelage. Immunologic staining of corneal samples suggested an
      inflammatory response with signs of neovascularization in half of the affected
      older mice. While the corneal phenotype was observed at irregular time points,
      mainly after 6 months, its appearance coincided with a degeneration of Meibomian
      glands in the eyelids of affected animals. Conclusions: The mutation described
      herein is associated with inflammation and neovascularization of corneal tissue.
      Simultaneous degeneration of Meibomian glands in affected animals suggested a
      change in tear-film composition as the underlying cause for the corneal
      phenotype. Our data further support that different pathogenic mechanisms underlie
      some of the reported mutations in Gsdma3.

PMID- 29372255
TI  - Outer Retinal Dysfunction in the Absence of Structural Abnormalities in Multiple
      Sclerosis.
AB  - Purpose: Recent evidence suggests structural changes distal to the inner retina
      in multiple sclerosis (MS) patients. The functional correlates of these proposed
      structural abnormalities remain unclear. We investigated outer retinal function
      and structure in MS patients, and quantified to what extent outer retinal
      structure influenced function in these patients. Methods: Outer retinal function
      was assessed using the full-field and multifocal electroretinogram (ERG/MF-ERG),
      whereas retinal structure was assessed using spectral-domain optical coherence
      tomography (OCT). Results were compared with preexisting normative data. The
      relationships between electrophysiology parameters and the OCT values
      corresponding to the proposed cellular origins of the ERG and MF-ERG were
      analyzed. Results: Most electrophysiological responses were delayed in MS
      patients, independently of optic neuritis (ON). Inner retinal thickness and
      volumes were reduced, and inner nuclear layer volume marginally increased, in
      eyes with previous ON; all other OCT parameters were normal. OCT results
      correlated with ERG amplitudes, but not with ERG peak times or any MF-ERG
      parameters. Conclusions: We recorded outer retinal dysfunction without detectable
      abnormalities of the corresponding retinal layers in MS patients, not ascribable
      to retrograde degeneration following ON. The findings complement a growing body
      of literature reporting primary retinal abnormalities distal to the ganglion cell
      inner plexiform layer complex in MS patients, with our data suggesting that this
      may be a more widespread phenomenon than previously thought. ERG may be of more
      utility in detecting retinal dysfunction in MS patients than MF-ERG. Analysis of
      peak times, rather than response amplitudes, is recommended.

PMID- 29372256
TI  - Dopamine Deficiency Mediates Early Rod-Driven Inner Retinal Dysfunction in
      Diabetic Mice.
AB  - Purpose: Electroretinograms (ERGs) are abnormal in diabetic retinas before the
      appearance of vascular lesions, providing a possible biomarker for diabetic
      vision loss. Previously, we reported that decreased retinal dopamine (DA) levels
      in diabetic rodents contributed to early visual and retinal dysfunction. In the
      current study, we examined whether oscillatory potentials (OPs) could serve as a
      potential marker for detecting early inner retinal dysfunction due to retinal DA
      deficiency. Methods: Retinal function was tested with dark-adapted ERGs, taken at
      3, 4, and 5 weeks after diabetes induction with streptozotocin. Electrical
      responses were analyzed and correlations were made with previously reported
      retinal DA levels. The effect of restoring systemic DA levels or removing DA from
      the retina in diabetic mice on OPs was assessed using L-3,4
      dihydroxyphenylalanine (L-DOPA) treatments and retina-specific tyrosine
      hydroxylase (Th) knockout mice (rTHKO), respectively. Results: Diabetic animals
      had significantly delayed OPs compared to control animals in response to dim, but
      not bright, flash stimuli. L-DOPA treatment preserved OP implicit time in
      diabetic mice. Diabetic rTHKO mice had further delayed OPs compared to diabetic
      mice with normal retinal Th, with L-DOPA treatment also providing benefit.
      Decreasing retinal DA levels significantly correlated with increasing OP delays
      mediated by rod pathways. Conclusions: Our data suggest that inner retinal
      dysfunction in early-stage diabetes is mediated by rod-pathway deficits and DA
      deficiencies. OP delays may be used to determine the earliest functional deficits
      in diabetic retinopathy and to establish an early treatment window for DA
      therapies that may prevent progressive vision loss.

PMID- 29372257
TI  - Rapid Detection and Identification of Uveitis Pathogens by Qualitative Multiplex
      Real-Time PCR.
AB  - Purpose: Infectious uveitis is a serious sight-threatening infection commonly
      caused by herpesviruses and Toxoplasma gondii. Etiologic diagnosis based on the
      clinical evaluation is often challenging. We developed and validated a multiplex
      real-time PCR assay coupled with high-resolution melting (HRM) for rapid
      detection and identification of herpes simplex viruses 1 and 2 (HSV-1 and HSV-2),
      varicella-zoster virus (VZV), cytomegalovirus (CMV), and T. gondii. Methods: The
      assay was designed to target pathogen genome regions that yield products with
      distinct melting temperatures. Analytical specificity, sensitivity, and precision
      of HRM identification were determined. Clinical validation was performed by
      testing 108 intraocular fluids collected from eyes suffering with infectious
      uveitis (n = 30) and controls (n = 78). Results: A nonoverlapping high-precision
      profile for each pathogen was generated following HRM (coefficient of variation
      0%). The assay was highly sensitive, with a limit of detection of 20 genome
      copies for herpesviruses and 200 genome copies for T. gondii. The intra- and
      interassay variability of cycle threshold (Ct) measurement was <=4% and <=6%,
      respectively. Thirteen intraocular specimens collected from suspected cases of
      infectious uveitis were positive (mean Ct values varied from 19.4 to 27.7).
      Melting profiles of positive cases were consistent with HSV-2 (n = 5), VZV (n =
      5), CMV (n = 2), and T. gondii (n = 1). Amplicon identities were confirmed by
      sequencing. Control intraocular samples from patients without a clinical
      diagnosis of infectious uveitis were all negative. Conclusions: This assay allows
      rapid, sensitive, and reliable detection and identification of the most common
      known causes of infectious uveitis, making early pathogen information-based
      intervention possible.

PMID- 29372258
TI  - Retinal Lesion Detection With Deep Learning Using Image Patches.
AB  - Purpose: To develop an automated method of localizing and discerning multiple
      types of findings in retinal images using a limited set of training data without
      hard-coded feature extraction as a step toward generalizing these methods to rare
      disease detection in which a limited number of training data are available.
      Methods: Two ophthalmologists verified 243 retinal images, labeling important
      subsections of the image to generate 1324 image patches containing either
      hemorrhages, microaneurysms, exudates, retinal neovascularization, or normal
      appearing structures from the Kaggle dataset. These image patches were used to
      train one standard convolutional neural network to predict the presence of these
      five classes. A sliding window method was used to generate probability maps
      across the entire image. Results: The method was validated on the eOphta dataset
      of 148 whole retinal images for microaneurysms and 47 for exudates. A pixel-wise
      classification of the area under the curve of the receiver operating
      characteristic of 0.94 and 0.95, as well as a lesion-wise area under the
      precision recall curve of 0.86 and 0.64, was achieved for microaneurysms and
      exudates, respectively. Conclusions: Regionally trained convolutional neural
      networks can generate lesion-specific probability maps able to detect and
      distinguish between subtle pathologic lesions with only a few hundred training
      examples per lesion.

PMID- 29372259
TI  - Lycium Barbarum Polysaccharides Protect Retina in rd1 Mice During Photoreceptor
      Degeneration.
AB  - Purpose: As an active component in wolfberry, lycium barbarum polysaccharides
      (LBP) are capable of protecting retinal neurons in several animal disease models.
      Here, we asked whether LBP rescues the retinal morphology and function in rd1
      mouse, a photoreceptor fast-degenerating animal model of retinitis pigmentosa,
      and in particular focused on LBP's effects on the function of retinal ganglion
      cells (RGCs) during photoreceptor degeneration. Methods: An equal volume of LBP
      or control vehicle was daily intraperitoneal (i.p.) injected in rd1 mice from
      postnatal day 4 (P4) to P14, P20, or P24 when photoreceptors completely
      degenerate. Immunostaining, electroretinogram (ERG), visual behavior tests and
      multielectrode array (MEA) recordings were assessed to determine the structure
      and function of the treated retina. Results: LBP treatment greatly promoted
      photoreceptor survival, enhanced ERG responses, and improved visual behaviors in
      rd1 mice. MEA data showed that LBP treatment in general decreased the abnormally
      high spontaneous spiking that occurs in rd1 mice, and increased the percentage of
      light-responsive RGCs as well as their light-evoked response, light sensitivity,
      signal-to-noise ratio, and response speed. Interestingly, LBP treatment affected
      ON and OFF responses differently. Conclusions: LBP improves retinal morphology
      and function in rd1 mice, and delays the functional decay of RGCs during
      photoreceptor degeneration. This is the first study that has examined in detail
      the effects of LBP on RGC responses. Our data suggest that LBP may help extend
      the effective time window before more invasive RP therapeutic approaches such as
      retinoprosthesis are applied.

PMID- 29372260
TI  - Comparison of outcome measures from different pathways following total knee
      arthroplasty.
AB  - INTRODUCTION: The benefits of extended inpatient rehabilitation following total
      knee arthroplasty (TKA) in local community hospitals (CHs) are unproven. Our
      study compared functional outcomes between patients discharged home and to CHs
      following TKA. METHODS: A case-control study was conducted of patients undergoing
      primary unilateral TKA. Consecutive patients (n = 1,065) were retrospectively
      reviewed using the Knee Society Clinical Rating System (KSCRS), 36-item Short
      Form Health Survey (SF-36) and Oxford Knee Score (OKS) preoperatively, and at the
      six-month and two-year follow-ups. RESULTS: Overall, 967 (90.8%) patients were
      discharged home and 98 (9.2%) to CHs. CH patients were older (mean age 70.7 vs.
      67.2 years; p < 0.0001), female (86.7% vs. 77.5%; p = 0.0388) and less educated
      (primary education and above: 61.7% vs. 73.8%; p = 0.0081). Median CH length of
      stay was 23.0 (range 17.0-32.0) days. Significant predictors of discharge
      destination were older age, female gender, lower education, and poorer ambulatory
      status and physical health. Preoperatively, CH patients had worse KSCRS Function
      (49.2 +/- 19.5 vs. 54.4 +/- 16.8; p = 0.0201), SF-36 Physical Functioning (34.3
      +/- 22.6 vs. 40.4 +/- 22.2; p = 0.0017) and Social Functioning (48.2 +/- 35.1 vs.
      56.0 +/- 35.6; p = 0.0447) scores. CH patients had less improvement for all
      scores at all follow-ups. Regardless of preoperative confounders, with repeated
      analysis of variance, discharge destination was significantly associated with
      KSCRS, SF-36 and OKS scores. CONCLUSION: Older, female and less educated patients
      with poorer preoperative functional scores were more likely to be discharged to
      CHs after TKA. At the two-year follow-up, patients in CHs had less improvement in
      functional outcomes than those discharged home.

PMID- 29372261
TI  - Patients with primary restless legs syndrome have higher prevalence of autonomic
      dysfunction and irritable bowel syndrome.
AB  - INTRODUCTION: Given the limited data on autonomic dysfunction in patients with
      primary restless legs syndrome (pRLS), we compared autonomic dysfunction and
      presence of irritable bowel syndrome (IBS) between patients with pRLS and control
      patients. METHODS: Consecutive adult drug-naive patients with pRLS, and age- and
      gender-matched healthy control patients were enrolled in this study. Diagnoses,
      based on validated self-reported questionnaires, were made using the following
      guidelines: Rome III classification system for functional gastrointestinal
      disorders for IBS; Beck Anxiety Inventory (BAI) and Beck Depression Inventory
      (BDI) for the presence of anxiety and depression, respectively; Pittsburgh Sleep
      Quality Index (PSQI) for severity of sleep disturbances; and Scales for Outcomes
      in Parkinson's disease-Autonomic (SCOPA-AUT) for autonomic dysfunction. RESULTS:
      There were 88 patients with pRLS (18 male, 70 female) and 128 control patients
      (40 men, 88 women). The mean age of the pRLS patients and control patients was
      50.3 +/- 9.3 years and 49.7 +/- 8.2 years, respectively. Overall, 41 (46.6%) of
      the patients with pRLS and 16 (12.5%) of the control patients had IBS. Among
      patients with pRLS, IBS was significantly more common and the total autonomic
      SCOPA-AUT scores were higher than those found among control patients. Among pRLS
      patients with IBS, total autonomic SCOPA-AUT, PSQI, BAI and BDI scores were
      significantly higher than among pRLS patients without IBS. The presence of IBS
      did not affect the severity of restless legs syndrome. CONCLUSION: The presence
      of autonomic nervous system impairment in patients with pRLS and the strong link
      between IBS and pRLS merit further, more extensive investigation.

PMID- 29372263
TI  - [E-Health and reality - what are we facing in patient care?]
AB  - The terms e-Health and digitization are core elements of a change in our time.
      The main drivers of this change - in addition to a dynamic market - are the
      serious advantages for the healthcare sector in the processing of tasks and
      requirements. The large amounts of data, the intensively growing medical
      knowledge, the rapidly advancing technological developments and the goal of a
      personalized, customized therapy for the patient, make the application absolutely
      necessary. While e-Health describes the use of information and communication
      technologies in healthcare, the concept of digitization is associated with the
      underlying processes of change and innovation. Digital technologies include
      software and hardware based developments. The term clinical data intelligence
      describes the property of workability and also characterizes the collaboration of
      clinically relevant systems with which the medical user works. The hierarchy in
      digital processing maps the levels from pure data management through clinical
      decision support to automated process flows and autonomously operating units. The
      combination of patient data management and clinical decision support proves its
      value in terms of error reduction, prevention, quality and safety, especially in
      drug therapy. The aim of this overview is the presentation of the existing
      reality in medical centers with perspectives derived from the point of view of
      the medical user.

PMID- 29372262
TI  - Vascular endothelium dysfunction: a conservative target in metabolic disorders.
AB  - AIM: Vascular endothelium plays a role in capillary transport of nutrients and
      drugs and regulates angiogenesis, homeostasis, as well as vascular tone and
      permeability as a major regulator of local vascular homeostasis. The present
      study has been designed to investigate the role of endothelium in metabolic
      disorders. METHODS: The endothelium maintains the balance between vasodilatation
      and vasoconstriction, procoagulant and anticoagulant, prothrombotic and
      antithrombotic mechanisms. RESULTS: Diabetes mellitus causes the activation of
      aldose reductase, polyol pathway and advanced glycation-end-product formation
      that collectively affect the phosphorylation status and expression of endothelial
      nitric oxide synthatase (eNOS) and causes vascular endothelium dysfunction.
      Elevated homocysteine levels have been associated with increase in LDL oxidation,
      generation of hydrogen peroxides, superoxide anions that increased oxidative
      degradation of nitric oxide. Hyperhomocysteinemia has been reported to increase
      the endogenous competitive inhibitors of eNOS viz L-N-monomethyl arginine (L
      NMMA) and asymmetric dimethyl arginine (ADMA) that may contribute to vascular
      endothelial dysfunction. Hypercholesterolemia stimulates oxidation of LDL
      cholesterol, release of endothelins, and generation of ROS. The increased
      cholesterol and triglyceride level and decreased protective HDL level, decreases
      the activity and expression of eNOS and disrupts the integrity of vascular
      endothelium, due to oxidative stress. Hypertension also stimulates release of
      endothelins, vasoconstrictor prostanoids, angiotensin II, inflammatory cytokines,
      xanthine oxidase and, thereby, reduces bioavailability of nitric oxide.
      CONCLUSION: Thus, the cellular and molecular mechanisms underlying diabetes
      mellitus, hyperhomocysteinemia, hypercholesterolemia hypertension and
      hyperuricemia leads to an imbalance of phosphorylation and dephosphorylation
      status of lipid and protein kinase that cause modulation of vascular endothelial
      L-arginine/nitric oxide synthetase (eNOS), to produce vascular endothelium
      dysfunction.

PMID- 29372264
TI  - [Lichenoid drug reactions].
AB  - Lichenoid drug reactions are rare compared to typical morbilliform drug exanthema
      or urticaria. They are associated with specific drugs or drug families like gold,
      antimalarial drugs, beta-blockers and angiotensin-converting-enzyme inhibitors.
      Recent observations included associations with novel drugs such as biologics (e.
      g. tumour necrosis factor antagonists) and immune checkpoint inhibitors (anti
      programme cell death protein 1 antibodies). Lichenoid drug reactions most often
      resemble lichen planus mainly in areas of ultraviolet-light exposed skin, but
      also mucosal lichen planus and even bullous lesions may occur.

PMID- 29372265
TI  - Percutaneous cholecystostomy for severe (Tokyo 2013 stage III) acute
      cholecystitis.
AB  - PURPOSES: To evaluate the impact of percutaneous cholecystostomy (PC) on severe
      acute cholecystitis (AC). METHODS: According to the ICD-9 classification, we
      retrospectively retrieved medical records of patients discharged with a diagnosis
      of AC from January 2007 to December 2016 at our hospital. Patients were then
      stratified according to the Tokyo 2013 (TG 13) AC severity criteria. Grade III AC
      was diagnosed according to the TG 13 criteria. Indications for PC were failure of
      optimal medical treatment within 48 h, worsening of clinical condition within
      early medical treatment, patients unfit for upfront surgery and patient's
      preference. Ascites was considered a contraindication to PC while coagulopathy
      was considered a minor contraindication. Primary end points were: clinical
      improvement, morbidity and related mortality. Secondary endpoints were AC
      recurrences and elective laparoscopic cholecystectomies (LS). Response was
      evaluated by clinical and blood test improvement. Morbidity was evaluated
      according to the Dindo-Clavien scale. RESULTS: A total of 117 eligible patients
      were diagnosed as grade III AC. Of these, 29 (24.7%) underwent PC. The procedure
      was completed in all cases. Overall morbidity rate was 20.6%. Main complication
      was the drainage dislodgement due to involuntary patient's movement. Overall
      mortality was 17.2% but no causes of death were dependent upon the procedure.
      Clinical improvement was reported in 95.5% of surviving patients. CONCLUSION:
      This study confirms that PC is a valuable tool in the treatment of severe AC.
      Randomized trials are needed to clarify the criteria for patient selection and to
      optimize the timing for both cholecystostomy and cholecystectomy.

PMID- 29372266
TI  - [Leiomyosarcoma of the foreskin : A rare case of mesenchymal foreskin tumor].
AB  - We report a case of a rare mesenchymal foreskin tumor. A slow-growing node was
      detected during the urological examination of a 39-year-old man. A histological
      examination following the node excision showed a superficial leiomyosarcoma.
      Superficial leiomyosarcomas rarely metastasize and are associated with a better
      prognosis than deeper tumors. The patient had no relapse 9 months after a
      successful radical circumcision. We strongly recommend a histological examination
      whenever a growing node in the genital area is found.

PMID- 29372267
TI  - Discussion: Management of Tuberous Breast Deformities: Review of Long-Term
      Outcomes and Patient Satisfaction with BREAST-Q.

PMID- 29372268
TI  - Outcomes of Fat-Augmented Latissimus Dorsi (FALD) Flap Versus Implant-Based
      Latissimus Dorsi Flap for Delayed Post-radiation Breast Reconstruction.
AB  - BACKGROUND: Although free abdominal flaps constitute the gold standard in post
      radiation delayed breast reconstruction, latissimus dorsi-based methods offer
      alternative reconstructive options. This retrospective study aims to compare
      outcomes of delayed breast reconstruction using the fat-augmented latissimus
      dorsi (FALD) autologous reconstruction and the latissimus dorsi-plus-implant
      reconstruction in irradiated women. METHODS: We reviewed the files of 47 post
      mastectomy irradiated patients (aged 29-73 years), who underwent delayed
      latissimus dorsi-based breast reconstruction between 2010 and 2016. Twenty-three
      patients (Group A) had an extended FALD flap and twenty-four patients (Group B)
      an implant-based latissimus dorsi reconstruction. Patients' age, BMI,
      pregnancies, volume of injected fat, implant size, postoperative complications,
      and secondary surgical procedures were recorded and analyzed. RESULTS: Age, BMI,
      pregnancies, and donor-site complications were similar in both groups (p > 0.05).
      Mean fat volume injected initially was 254 cc (ranged 130-380 cc/session); mean
      implant volume was 323 cc (ranged 225-420 cc). Breast complications were
      significantly fewer in Group A (one wound dehiscence, two oily cysts) compared to
      Group B (three cases with wound dehiscence, two extrusions, thirteen severe
      capsular contractions). Non-statistically significant difference was documented
      for secondary procedures between groups; although the mean number of additional
      surgeries/patient was higher in Group A, they referred to secondary lipofilling,
      whereas in Group B they were revision surgeries for complications. CONCLUSIONS:
      The FALD flap constitutes an alternative method for delayed autologous
      reconstruction after post-mastectomy irradiation, avoiding implant-related
      complications. Although additional fat graft sessions might be required, it
      provides an ideal autogenous reconstructive option for thin nulliparous women,
      with a small opposite breast and adequate fat donor sites. LEVEL OF EVIDENCE IV:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 29372269
TI  - Traumatic fractures as a result of motor vehicle collisions in children and
      adolescents.
AB  - PURPOSE: We investigated the incidence and pattern of traumatic fractures
      resulting from motor vehicle collisions in a population of children and
      adolescents (<=18 years old) and to determine the risk factors for nerve injury.
      METHODS: We retrospectively reviewed 734 patients admitted to our university
      affiliated hospitals from 2001 to 2010. RESULTS: This study enrolled 498 male
      (67.8%) and 236 female (32.2%) patients aged 10.9 +/- 5.3 years old. The most
      common injuries were to pedestrians, and the most common fracture sites (438,
      59.7%) were to lower extremities (n = 441, 60.0%). A total of 201 (27.4%)
      patients experienced a nerve injury. Univariate logistic regression analysis
      showed that age (P = 0.014), lower-extremity (P = 0.000), craniofacial (P =
      0.000) and spinal (P = 0.000) fractures were risk factors for nerve injury.
      Multivariate logistic regression analysis indicated that craniofacial [odds ratio
      (OR) = 9.003, 95% confidence interval (CI) 5.159-15.711, P = 0.000)] and spinal
      (experiencedOR = 10.141, 95% CI: 4.649-22.121, P = 0.011) fractures were
      independent risk factors for nerve injury. CONCLUSIONS: Patients in the 15- to 18
      years old group and drivers had the largest sex ratio and highest frequencies of
      both nerve injury and early complications. Craniofacial and spinal fractures were
      independent risk factors for nerve injury. It is therefore important to focus on
      these risk factors to determine the presence of a nerve injury so that early,
      timely diagnosis and targeted treatment can be provided.

PMID- 29372270
TI  - Letter regarding article by Sun et al.: Locking plates versus intramedullary
      nails in the management of displaced proximal humeral fractures: a systematic
      review and meta-analysis.

PMID- 29372271
TI  - Current Status and Future Prospects of Next-Generation Data Management and
      Analytical Decision Support Tools for Enhancing Genetic Gains in Crops.
AB  - Agricultural disciplines are becoming data intensive and the agricultural
      research data generation technologies are becoming sophisticated and high
      throughput. On the one hand, high-throughput genotyping is generating petabytes
      of data; on the other hand, high-throughput phenotyping platforms are also
      generating data of similar magnitude. Under modern integrated crop breeding,
      scientists are working together by integrating genomic and phenomic data sets of
      huge data volumes on a routine basis. To manage such huge research data sets and
      use them appropriately in decision making, Data Management Analysis & Decision
      Support Tools (DMASTs) are a prerequisite. DMASTs are required for a range of
      operations including generating the correct breeding experiments, maintaining
      pedigrees, managing phenotypic data, storing and retrieving high-throughput
      genotypic data, performing analytics, including trial analysis, spatial
      adjustments, identifications of MTAs, predicting Genomic Breeding Values (GEBVs),
      and various selection indices. DMASTs are also a prerequisite for understanding
      trait dynamics, gene action, interactions, biology, GxE, and various other
      factors contributing to crop improvement programs by integrating data generated
      from various science streams. These tools have simplified scientists' lives and
      empowered them in terms of data storage, data retrieval, data analytics, data
      visualization, and sharing with other researchers and collaborators. This chapter
      focuses on availability, uses, and gaps in present-day DMASTs. Graphical
      Abstract.

PMID- 29372272
TI  - Combined evaluation of regional coronary artery calcium and myocardial perfusion
      by 82Rb PET/CT in the identification of obstructive coronary artery disease.
AB  - PURPOSE: Cardiac imaging with PET/CT allows measurement of coronary artery
      calcium (CAC), myocardial perfusion and coronary vascular function. We
      investigated whether the combined assessment of regional CAC score, ischemic
      total perfusion deficit (ITPD) and quantitative coronary vascular function would
      further improve the diagnostic accuracy of PET/CT in predicting obstructive
      coronary artery disease (CAD). METHODS: We analyzed 113 patients with suspected
      CAD referred to 82Rb PET/CT myocardial perfusion imaging with available coronary
      angiographic data. Obstructive CAD was defined as >=75% stenosis. The receiver
      operating characteristic area under curve (AUC) was applied to evaluate the
      ability of CAC score, ITPD, hyperemic myocardial blood flow (MBF) and coronary
      flow reserve (CFR) to identify CAD. RESULTS: Vessels with obstructive CAD (71
      vessels) had higher ITPD (4.6 +/- 6.2 vs. 0.6 +/- 1.3) and lower hyperemic MBF
      (1.01 +/- 0.5 vs. 1.75 +/- 0.6 ml/min/g) and CFR (1.56 +/- 0.6 vs. 2.38 +/- 0.7;
      all p < 0.001) than those without. In prediction of per-vessel CAD, the AUCs for
      the models including CAC/ITPD/hyperemic MBF (0.869) and CAC/ITPD/CFR (0.875) were
      higher (both p < 0.01) than for the model including CAC/ITPD (0.790). Compared
      with CAC/ITPD, continuous net reclassification improvement was 0.69 (95%
      bootstrap confidence interval, CI, 0.365-1.088) for the CAC/ITPD/hyperemic MBF
      model and 0.99 (95% bootstrap CI 0.64-1.26) for the CAC/ITPD/CFR model.
      CONCLUSION: Hyperemic MBF and CFR provide incremental information about the
      presence of CAD over CAC score and perfusion imaging parameters. The combined use
      of CAC, myocardial perfusion imaging and quantitative coronary vascular function
      in may help predict more accurately the presence of obstructive CAD.

PMID- 29372273
TI  - Extraction and detection of bisphenol A in human serum and urine by aptamer
      functionalized magnetic nanoparticles.
AB  - A new type of magnetic nanoparticles (MNPs), as the absorbents of bisphenol A
      (BPA), was prepared by functionalization of Fe3O4@SiO2 with BPA-specific aptamer
      in this work. ssDNA aptamer was immobilized on the Fe3O4@SiO2 surface through
      biotin-avidin interactions, playing a role of the specific probe for BPA. The
      resultant materials (Apt-MNPs) exhibited outstanding magnetic responsibility and
      can be separated efficiently by the magnetic field. Experimental results also
      showed that Apt-MNPs had large adsorption capacity and high competitive
      selectivity for the targeted compound BPA. Furthermore, Apt-MNPs were adopted as
      the specific absorbents to extract and enrich BPA from human serum and urine
      samples. Therefore, an efficient detection method of BPA was developed in
      combination with high-performance liquid chromatography (HPLC). The linearity of
      the method was over a range of 5-10,000 ng mL-1 with a correlation coefficient of
      0.99997, and the limit of detections (LODs) for serum and urine were 2.0 and 1.0
      ng mL-1, respectively. The recoveries of BPA in the spiked human serum and urine
      samples were 90.8 +/- 7.3% (RSD) and 92.3 +/- 1.5%, respectively. Our results
      demonstrated that Apt-MNPs were high-performance adsorbents for extracting and
      enriching BPA, resulting in fast and efficient detection of BPA in serum and
      urine samples. Graphical abstract Aptamer-MNPs were effective for BPA separation
      from serum and urine.

PMID- 29372274
TI  - A comprehensive evaluation of tyrosol and hydroxytyrosol derivatives in extra
      virgin olive oil by microwave-assisted hydrolysis and HPLC-MS/MS.
AB  - A rapid and reliable method to assay the total amount of tyrosol and
      hydroxytyrosol derivatives in extra virgin olive oil has been developed. The
      methodology intends to establish the nutritional quality of this edible oil
      addressing recent international health claim legislations (the European
      Commission Regulation No. 432/2012) and changing the classification of extra
      virgin olive oil to the status of nutraceutical. The method is based on the use
      of high-performance liquid chromatography coupled with tandem mass spectrometry
      and labeled internal standards preceded by a fast hydrolysis reaction step
      performed through the aid of microwaves under acid conditions. The overall
      process is particularly time saving, much shorter than any methodology previously
      reported. The developed approach represents a mix of rapidity and accuracy whose
      values have been found near 100% on different fortified vegetable oils, while the
      RSD% values, calculated from repeatability and reproducibility experiments, are
      in all cases under 7%. Graphical abstract Schematic of the methodology applied to
      the determination of tyrosol and hydroxytyrosol ester conjugates.

PMID- 29372275
TI  - Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older
      Men: Findings from the Hertfordshire Sarcopenia Study (HSS).
AB  - Sarcopenia and osteoporosis are associated with poor health outcomes in older
      people. Relationships between muscle and bone have typically been reported at a
      functional or macroscopic level. The aims of this study were to describe the
      relationships between muscle morphology and bone health among participants of the
      Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5)
      years, were recruited into the HSS. Whole body lean mass as well as appendicular
      lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone
      mineral density (BMD) were obtained through dual-energy X-ray absorptiometry
      scanning. Percutaneous biopsy of the vastus lateralis was performed successfully
      in 99 participants. Image analysis was used to determine the muscle morphology
      variables of slow-twitch (type I) and fast-twitch (type II) myofibre area,
      myofibre density, capillary and satellite cell (SC) density. There were strong
      relationships between whole and appendicular lean body mass in relation to
      femoral neck BMC and BMD (r >= 0.43, p < 0.001). Type II fibre area was
      associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p =
      0.01) with relationships robust to adjustment for age and height. In unadjusted
      analysis, SC density was associated with whole body area (r = 0.30, p = 0.011)
      and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral
      neck. We have demonstrated associations between BMC and changes in muscle at a
      cellular level predominantly involving type II myofibres. Interventions targeted
      at improving muscle mass, function and quality may improve overall
      musculoskeletal health. Larger studies that include women are needed to explore
      these relationships further.

PMID- 29372277
TI  - Hand MRI and the Greulich-Pyle atlas in skeletal age estimation in adolescents.
AB  - OBJECTIVE: To evaluate the feasibility of hand MRI in age assessment in
      adolescents using the Greulich-Pyle (GP) atlas criteria. MATERIALS AND METHODS:
      Two radiologists, who were blinded to the study subjects' chronologic ages, semi
      objectively evaluated 1.5-T MRIs of the left hands of ten patients (13.5 +/- 2.6
      years) who had left-hand radiographs and 50 healthy volunteers (15 +/- 2 years).
      RESULTS: A coronal T1-weighted, volumetric, interpolated, breath-hold examination
      with water excitation (T1 VIBE-3D-WE) achieved the best image quality. The
      correlation between estimated patients' ages on radiographs and MRI was high. The
      average estimated age difference between the MRIs and radiographs was -0.05 years
      for reader 1 and -0.175 years for reader 2. The interclass coefficients (ICCs)
      showed high interobserver agreement (radiographs: ICC = 0.95, MRI: ICC = 0.97).
      The ICC, calculated separately for the male and female volunteers' estimated ages
      by MRI, also showed a high agreement between the two readers (male: ICC = 0.97,
      female: ICC = 0.95). Reader 1 estimated 94% of volunteers within 2 standard
      deviations (SD) and 62% within 1 SD. The results for reader 2 were 92% and 54%,
      respectively. Thirty-nine percent of girls and 27% of boys were estimated to be
      older using 1 SD. CONCLUSION: MRI of the left hand is a feasible alternative to
      hand radiographs for skeletal age estimation in adolescents using the GP criteria
      with 2 SD. Using 1 SD, the age of healthy volunteers tended to be estimated as
      higher than the chronologic age. Future studies should evaluate the results in a
      larger number of participants.

PMID- 29372278
TI  - Isolation and characterization of a novel bacteriophage infecting Vibrio
      alginolyticus.
AB  - Vibrio alginolyticus is a common marine bacterium implicated in disease outbreaks
      in marine farmed fish and invertebrates. Due to the inappropriate use of
      antibiotics in aquaculture, alternative therapies have been proposed. One of the
      most promising options is the use of lytic bacteriophages to control pathogenic
      bacteria. This work describes the isolation and characterization of a lytic phage
      (VEN) against a V. alginolyticus strain (V2) isolated from a disease outbreak in
      common dentex (Dentex dentex) cultured at the Hellenic Centre for Marine Research
      (HCMR) in Crete, Greece. The bacteriophage is morphologically similar to phages
      from Podoviridae family and remained stable for 1 year at 4  degrees C and over 1
      h when kept at 50  degrees C. VEN was able to lyse the host bacteria at several
      multiplicity of infection (MOI) (0.1-100) in liquid cultures. However, it was
      unable to infect other V. alginolyticus strains. Its genome consists of 44,603 bp
      with a GC content of 43.5%, while sequence analysis revealed the presence of 54
      potential ORFs with a T7-like genomic organization. Almost 65% of the predicted
      ORFs presented homology with proteins of the vibriophages Vc1 and phi-A318
      infecting Vibrio cyclitrophicus and Vibrio alginolyticus, respectively.
      Phylogenetic analysis applying the amino acid sequence of the large terminase
      subunit confirmed the close relationship of these phages. Furthermore, the
      comparison of the RNA polymerase of these phages revealed that the motifs A, B
      and C related to the catalytic activity and the recognition loop related to
      promotor identification were also conserved. VEN has an obligate lytic life cycle
      demonstrated by experimental data and genomic analysis. These results suggest
      that VEN may provide a good candidate to control recurrent diseases caused by V.
      alginolyticus at HCMR.

PMID- 29372280
TI  - Correction to: Routine Sildenafil Does Not Improve Clinical Outcomes After Fontan
      Operation.
AB  - The original version of this article unfortunately contained a mistake. The
      presentation of Table 2 was incorrect .The corrected table is given below.

PMID- 29372279
TI  - Blood pressure targets in type 2 diabetes. Evidence against or in favour of an
      aggressive approach.
AB  - When associated with high blood pressure, type 2 diabetes mellitus is
      characterised by a high risk of adverse cardiovascular (CV) and renal outcomes.
      However, both can be effectively reduced by antihypertensive treatment. Current
      guidelines on the treatment of hypertension emphasize the need to effectively
      treat high blood pressure in diabetic individuals, but their recommendations
      differ in terms of the optimal target blood pressure value to aim for in order to
      maximise CV and renal protection. In some guidelines the recommended target blood
      pressure values are <140/90 mmHg (systolic/diastolic), whereas in others, blood
      pressure values close or even less than 130/80 mmHg are recommended. This paper
      will discuss the evidence for and against a conservative or more aggressive blood
      pressure target for treated diabetic hypertensive individuals based on the
      evidence provided by randomised trials, trial meta-analyses and large
      observational studies. Based on the available evidence, it appears that blood
      pressure targets will probably have to be lower than <140/90 mmHg, and that
      values approaching 130/80 mmHg should be recommended. However, evidence in favour
      of even lower systolic values, i.e. <130 mmHg, is limited and is definitively
      against a reduction to <120 mmHg.

PMID- 29372281
TI  - Characterization of the Gut Microbiota in Six Geographical Populations of Chinese
      Rhesus Macaques (Macaca mulatta), Implying an Adaptation to High-Altitude
      Environment.
AB  - Knowledge about the impact of different geographical environments on rhesus
      macaque gut microbiota is limited. In this study, we compared the characteristics
      of gut microbiota in six different Chinese rhesus macaque populations, including
      Hainan, Nanning, Guizhou, Xichang, Jianchuan and Tibet. Through the composition
      analysis of operational taxonomic units (OTUs), we found that there were
      significant differences in the abundance of core overlapping OTUs in the six
      Chinese groups. Specifically, the Tibet population exhibited the highest gut
      microbial diversity and the most unique OTUs. Statistically significant
      differences in the composition of gut microbiota among the six groups at phylum
      and family level were evident. Specifically, Tibet had higher abundances of
      Firmicutes and lower abundances of Bacteroidetes than the other geographical
      groups, and the higher abundance of Firmicutes in the Tibetan group was mainly
      caused by a significant increase in the family Ruminococcaceae and
      Christensenellaceae. Phylogenetic investigation of communities by reconstruction
      of unobserved state analysis showed that the enrichment ratio for environmental
      information processing and organismal systems was the highest in the Tibet
      population. Additionally, our results suggested that in the adaptation process of
      rhesus macaques to different geographical environments, the abundance of the core
      common flora of the intestinal microbes had undergone varying degree of change
      and produced new and unique flora, both of which helped to reshape the gut
      microbiota of rhesus macaques. In particular, this change was more obvious for
      animals in the high-altitude environments.

PMID- 29372283
TI  - Construction of a genome-anchored, high-density genetic map for melon (Cucumis
      melo L.) and identification of Fusarium oxysporum f. sp. melonis race 1
      resistance QTL.
AB  - KEY MESSAGE: Four QTLs and an epistatic interaction were associated with disease
      severity in response to inoculation with Fusarium oxysporum f. sp. melonis race 1
      in a recombinant inbred line population of melon. The USDA Cucumis melo inbred
      line, MR-1, harbors a wealth of alleles associated with resistance to several
      major diseases of melon, including powdery mildew, downy mildew, Alternaria leaf
      blight, and Fusarium wilt. MR-1 was crossed to an Israeli cultivar, Ananas
      Yok'neam, which is susceptible to all of these diseases, to generate a
      recombinant inbred line (RIL) population of 172 lines. In this study, the RIL
      population was genotyped to construct an ultra-dense genetic linkage map with
      5663 binned SNPs anchored to the C. melo genome and exhibits the overall high
      quality of the assembly. The utility of the densely genotyped population was
      demonstrated through QTL mapping of a well-studied trait, resistance to Fusarium
      wilt caused by Fusarium oxysporum f. sp. melonis (Fom) race 1. A major QTL co
      located with the previously validated resistance gene Fom-2. In addition, three
      minor QTLs and an epistatic interaction contributing to Fom race 1 resistance
      were identified. The MR-1 * AY RIL population provides a valuable resource for
      future QTL mapping studies and marker-assisted selection of disease resistance in
      melon.

PMID- 29372282
TI  - Mapping resistance to powdery mildew in barley reveals a large-effect nonhost
      resistance QTL.
AB  - KEY MESSAGE: Resistance factors against non-adapted powdery mildews were mapped
      in barley. Some QTLs seem effective only to non-adapted mildews, while others
      also play a role in defense against the adapted form. The durability and
      effectiveness of nonhost resistance suggests promising practical applications for
      crop breeding, relying upon elucidation of key aspects of this type of
      resistance. We investigated which genetic factors determine the nonhost status of
      barley (Hordeum vulgare L.) to powdery mildews (Blumeria graminis). We set out to
      verify whether genes involved in nonhost resistance have a wide effectiveness
      spectrum, and whether nonhost resistance genes confer resistance to the barley
      adapted powdery mildew. Two barley lines, SusBgtSC and SusBgtDC, with some
      susceptibility to the wheat powdery mildew B. graminis f.sp. tritici (Bgt) were
      crossed with cv Vada to generate two mapping populations. Each population was
      assessed for level of infection against four B. graminis ff.spp, and QTL mapping
      analyses were performed. Our results demonstrate polygenic inheritance for
      nonhost resistance, with some QTLs effective only to non-adapted mildews, while
      others play a role against adapted and non-adapted forms. Histology analyses of
      nonhost interaction show that most penetration attempts are stopped in
      association with papillae, and also suggest independent layers of defence at
      haustorium establishment and conidiophore formation. Nonhost resistance of barley
      to powdery mildew relies mostly on non-hypersensitive mechanisms. A large-effect
      nonhost resistance QTL mapped to a 1.4 cM interval is suitable for map-based
      cloning.

PMID- 29372284
TI  - Do modern total knee replacements improve tibial coverage?
AB  - PURPOSE: The purpose of the present study is to compare newer designs of various
      symmetric and asymmetric tibial components and measure tibial bone coverage using
      the rotational safe zone defined by two commonly utilized anatomic rotational
      landmarks. METHODS: Computed tomography scans (CT scans) of one hundred
      consecutive patients scheduled for total knee arthroplasty were obtained pre
      operatively. A virtual proximal tibial cut was performed and two commonly used
      rotational axes were added for each image: the medio-lateral axis (ML-axis) and
      the medial 1/3 tibial tubercle axis (med-1/3-axis). Different symmetric and
      asymmetric implant designs were then superimposed in various rotational positions
      for best cancellous and cortical coverage. The images were imported to a public
      domain imaging software, and cancellous and cortical bone coverage was computed
      for each image, with each implant design in various rotational positions.
      RESULTS: One single implant type could not be identified that provided the best
      cortical and cancellous coverage of the tibia, irrespective of using the med-1/3
      axis or the ML-axis for rotational alignment. However, it could be confirmed that
      the best bone coverage was dependent on the selected rotational landmark.
      Furthermore, improved bone coverage was observed when tibial implant positions
      were optimized between the two rotational axes. CONCLUSIONS: Tibial coverage is
      similar for symmetric and asymmetric designs, but depends on the rotational
      landmark for which the implant is designed. The surgeon has the option to improve
      tibial coverage by optimizing placement between the two anatomic rotational
      alignment landmarks, the medial 1/3 and the ML-axis. Surgeons should be careful
      assessing intraoperative rotational tibial placement using the described anatomic
      rotational landmarks to optimize tibial bony coverage without compromising
      patella tracking. LEVEL OF EVIDENCE: III.

PMID- 29372285
TI  - Comparison of inflammatory urine markers in patients with interstitial cystitis
      and overactive bladder.
AB  - INTRODUCTION AND HYPOTHESIS: Chronic inflammatory conditions seem to be a shared
      characteristic in patients with interstitial cystitis (IC) and overactive bladder
      (OAB). Thus, we measured 40 inflammatory urine markers in IC patients with or
      without Hunner's lesions (HIC and NHIC respectively) and OAB patients. METHODS:
      Urine was collected from consecutive HIC patients, NHIC patients, and age and
      gender-matched OAB patients with no history of IC, recurrent urinary tract
      infection or bladder cancer. The diagnosis of IC was based on the Asian IC
      guideline criteria. A representative 40 inflammatory growth factors, cytokines,
      and chemokines in urine were measured using a MILLIPLEX immunoassay kit.
      Statistical differences in these markers among the groups were determined by
      nonparametric ANOVA followed by multiple comparison test. The diagnostic
      efficiency of these markers was measured using receiver operating characteristic
      analysis. RESULTS: Vascular endothelial growth factor (VEGF), interleukin-1alpha
      (IL-1alpha), IL-6, and chemokines including CCL2, CCL5, CXCL1, CXCL8, and CXCL10
      were significantly increased in HIC (n = 30) and NHIC (n = 30) patients compared
      with OAB (n = 28) patients. The significant increases in CXCL8 and CXCL10 were
      also found in HIC patients compared with NHIC patients. However, there were no
      significant differences in the other urine markers among the groups. Area under
      the curves for VEGF, CXCL10, CXCL8, IL-1alpha, CCL5, CCL2, IL-6, and CXCL1 to
      detect IC in these patients were 0.87, 0.86, 0.81, 0.80, 0.80, 0.71, 0.66, and
      0.50 respectively. CONCLUSIONS: The increases in angiogenesis-associated proteins
      such as VEGF and CXCL10 may be pathophysiologically important for the development
      of IC.

PMID- 29372286
TI  - Generalized q-sampling imaging fiber tractography reveals displacement and
      infiltration of fiber tracts in low-grade gliomas.
AB  - PURPOSE: Low-grade gliomas (LGGs) are slow growing brain tumors that often cause
      displacement and/or infiltration of the surrounding white matter pathways.
      Differentiation between infiltration and displacement of fiber tracts remains a
      challenge. Currently, there is no reliable noninvasive imaging method capable of
      revealing such white matter alteration patterns. We employed quantitative
      anisotropy (QA) derived from generalized q-sampling imaging (GQI) to identify
      patterns of fiber tract alterations by LGGs. METHODS: Sixteen patients with a
      neuropathological diagnosis of LGG (WHO grade II) were enrolled. Peritumoral
      fiber tracts underwent qualitative and quantitative evaluation. Contralateral
      hemisphere counterparts were used for comparison. Tracts were qualitatively
      classified as unaffected, displaced, infiltrated or displaced, and infiltrated at
      once. The average QA of whole tract (W), peritumoral tract segment (S), and their
      ratio (S/W) were obtained and compared to the healthy side for quantitative
      evaluation. RESULTS: Qualitative analysis revealed 9 (13.8%) unaffected, 24
      (36.9%) displaced, 13 (20%) infiltrated, and 19 (29.2%) tracts with a combination
      of displacement and infiltration. There were no disrupted tracts. There was a
      significant increase in S/W ratio among displaced tracts in the pre-operative
      scans in comparison with the contralateral side. QA values of peritumoral tract
      segments (S) were significantly lower in infiltrated tracts. CONCLUSION: WHO
      grade II LGGs might displace, infiltrate, or cause a combination of displacement
      and infiltration of WM tracts. QA derived from GQI provides valuable information
      that helps to differentiate infiltration from displacement. Anisotropy changes
      correlate with qualitative alterations, which may serve as a potential biomarker
      of fiber tract integrity.

PMID- 29372287
TI  - Poor glycaemic control and its metabolic and demographic risk factors in a
      Malaysian community-based study.
AB  - OBJECTIVES: The lack of population-based evidence on the risk factors for poor
      glycaemic control in diabetics, particularly in resource-poor settings, is a
      challenge for the prevention of long-term complications. This study aimed to
      identify the metabolic and demographic risk factors for poor glycaemic control
      among diabetics in a rural community in Malaysia. METHODS: A total of 1844 (780
      males and 1064 females) known diabetics aged >= 35 years were identified from the
      South East Asia Community Observatory (SEACO) health and demographic surveillance
      site database. RESULTS: 41.3% of the sample had poor glycaemic control. Poor
      glycaemic control was associated with age and ethnicity, with older participants
      (65+) better controlled than younger adults (45-54), and Malaysian Indians most
      poorly controlled, followed by Malay and then Chinese participants. Metabolic
      risk factors were also highly associated with poor glycaemic control.
      CONCLUSIONS: There is a critical need for evidence for a better understanding of
      the mechanisms of the associations between risk factors and glycaemic control.

PMID- 29372288
TI  - Retrospective inconsistent analysis cannot validate safety of a treatment
      strategy.

PMID- 29372289
TI  - ?

PMID- 29372290
TI  - Patient positioning in head and neck cancer : Setup variations and safety margins
      in helical tomotherapy.
AB  - OBJECTIVE: To evaluate the interfractional variations of patient positioning
      during intensity-modulated radiotherapy (IMRT) with helical tomotherapy in head
      and neck cancer and to calculate the required safety margins (sm) for bony
      landmarks resulting from the necessary table adjustments. MATERIALS AND METHODS:
      In all, 15 patients with head and neck cancer were irradiated using the Hi-Art II
      tomotherapy system between April and September 2016. Before therapy sessions,
      patient position was frequently checked by megavolt computed tomography (MV-CT).
      Necessary table adjustments (ta) in the right-left (rl), superior-inferior (si)
      and anterior-posterior (ap) directions were recorded for four anatomical points:
      second, fourth and sixth cervical vertebral body (CVB), anterior nasal spine
      (ANS). Based upon these data sm were calculated for non-image-guided
      radiotherapy, image-guided radiotherapy (IGRT) and image guidance limited to a
      shortened area (CVB 2). RESULTS: Based upon planning CT the actual treatment
      required ta from -0.05 +/- 1.31 mm for CVB 2 (ap) up to 2.63 +/- 2.39 mm for ANS
      (rl). Considering the performed ta resulting from image control (MV-CT) we
      detected remaining ta from -0.10 +/- 1.09 mm for CVB 4 (rl) up to 1.97 +/- 1.64
      mm for ANS (si). After theoretical adjustment of patients position to CVB 2 the
      resulting ta ranged from -0.11 +/- 2.44 mm for CVB6 (ap) to 2.37 +/- 2.17 mm for
      ANS (si). These data imply safety margins: uncorrected patient position: 3.63
      9.95 mm, corrected positioning based upon the whole target volume (IGRT): 1.85
      6.63 mm, corrected positioning based upon CVB 2 (IGRT): 3.13-6.66 mm.
      CONCLUSIONS: The calculated safety margins differ between anatomic regions.
      Repetitive and frequent image control of patient positioning is necessary that,
      however, possibly may be focussed on a limited region.

PMID- 29372293
TI  - Human bone cellsin vitro.
AB  - Human bone cell cultures were established by maintaining collagenase-treated,
      bone fragments in low Ca++ medium. The resulting cell cultures exhibited a high
      level of alkaline phosphatase activity and produced a significant increase in
      intracellular cAMP when exposed to the 1-34 fragment of human parathyroid
      hormone. With continued culture, the cells formed a thick, extracellular matrix
      that mineralized when cultures were provided daily with normal levels of calcium,
      fresh ascorbic acid (50 MUg/ml) and 10 mM beta-glycerol phosphate.
      Biosynthetically, these cells produced type I collagen (without any type III
      collagen), and the bone-specific protein, osteonectin. In addition, the cells
      produced sulfated macromolecules electrophoretically identical to those
      positively identified as the bone proteoglycan in parallel cultures of fetal
      bovine bone cells. This technique provides a useful system for the study of
      osteoblast metabolismin vitro.

PMID- 29372291
TI  - Effects of shorter versus longer storage time of transfused red blood cells in
      adult ICU patients: a systematic review with meta-analysis and Trial Sequential
      Analysis.
AB  - PURPOSE: Patients in the intensive care unit (ICU) are often transfused with red
      blood cells (RBC). During storage, the RBCs and storage medium undergo changes,
      which may have clinical consequences. Several trials now have assessed these
      consequences, and we reviewed the present evidence on the effects of shorter
      versus longer storage time of transfused RBCs on outcomes in ICU patients.
      METHODS: We conducted a systematic review with meta-analyses and trial sequential
      analyses (TSA) of randomised clinical trials including adult ICU patients
      transfused with fresher versus older or standard issue blood. RESULTS: We
      included seven trials with a total of 18,283 randomised ICU patients; two trials
      of 7504 patients were judged to have low risk of bias. We observed no effects of
      fresher versus older blood on death (relative risk 1.04, 95% confidence interval
      (CI) 0.97-1.11; 7349 patients; TSA-adjusted CI 0.93-1.15), adverse events (1.26,
      0.76-2.09; 7332 patients; TSA-adjusted CI 0.16-9.87) or post-transfusion
      infections (1.07, 0.96-1.20; 7332 patients; TSA-adjusted CI 0.90-1.27). The
      results were unchanged by including trials with high risk of bias. TSA confirmed
      the results and the required information size was reached for mortality for a
      relative risk change of 20%. CONCLUSIONS: We may be able to reject a clinically
      meaningful effect of RBC storage time on mortality in transfused adult ICU
      patients as our trial sequential analyses reject a 10% relative risk change in
      death when comparing fresher versus older blood for transfusion.

PMID- 29372297
TI  - Genomic and functional characterisation of two Enterococcus strains isolated from
      Cotija cheese and their potential role in ripening.
AB  - Enterococcus spp. are present in the native microbiota of many traditional
      fermented foods. Their ability to produce antibacterial compounds, mainly against
      Listeria monocytogenes, has raised interest recently. However, there is scarce
      information about their proteolytic and lipolytic potential, and their
      biotechnological application is currently limited because enterococcal strains
      have been related to nosocomial infections. In this work, next-generation
      sequencing and optimised bioinformatic pipelines were used to annotate the
      genomes of two Enterococcus strains-one E. faecium and one E. faecalis-isolated
      from the Mexican artisanal ripened Cotija cheese. A battery of genes involved in
      their proteolytic system was annotated. Genes coding for lipases, esterases and
      other enzymes whose final products contribute to cheese aroma and flavour were
      identified as well. As for the production of antibacterial compounds, several
      peptidoglycan hydrolase- and bacteriocin-coding genes were identified in both
      genomes experimentally and by bioinformatic analyses. E. faecalis showed
      resistance to aminoglycosides and E. faecium to aminoglycosides and macrolides,
      as predicted by the genome functional annotation. No pathogenicity islands were
      found in any of the strains, although traits such as the ability of biofilm
      formation and cell aggregation were observed. Finally, a comparative genomic
      analysis was able to discriminate between the food strains isolated and
      nosocomial strains. In summary, pathogenic strains are resistant to a wide range
      of antibiotics and contain virulence factors that cause host damage; in contrast,
      food strains display less antibiotic resistance, include genes that encode class
      II bacteriocins and express virulence factors associated with host colonisation
      rather than invasion.

PMID- 29372298
TI  - Convenient synthetic approach for tri- and tetraprenylated cyclodipeptides by
      consecutive enzymatic prenylations.
AB  - The prenyltransferases EchPT1 and EchPT2 from Aspergillus ruber are responsible
      for the consecutive prenylations of cyclo-L-Trp-L-Ala, leading to the formation
      of the triprenylated echinulin as the predominant product. In this study, we
      demonstrate that EchPT1 also accepts all stereoisomers of cyclo-Trp-Ala and cyclo
      Trp-Pro and catalyses regiospecific reverse C2-prenylation at the indole nucleus.
      EchPT1 products were well accepted by EchPT2 for multiple consecutive
      prenylations, with conversion yields of 84 to 98% for six of the eight
      substrates. C2-, C5- and C7-triprenylated derivatives are identified as major
      enzyme products, with product yields of 40 to 86% in seven cases. High product
      yields of 25-36%, i.e. approximate 30% of the total enzyme products, were
      observed for tetraprenylated derivatives in the four reaction mixtures with one D
      and one L-configured amino acid residues. To the best of our knowledge,
      enzymatic preparation of tetraprenylated cyclodipeptides with such high efficacy
      has not been reported prior to this study.

PMID- 29372299
TI  - Enzymatic synthesis of avermectin B1a glycosides for the effective prevention of
      the pine wood nematode Bursaphelenchus xylophilus.
AB  - Avermectin produced by Streptomyces avermitilis is an anti-nematodal agent
      against the pine wood nematode Bursaphelenchus xylophilus. However, its potential
      usage is limited by its poor water solubility. For this reason, continuous
      efforts are underway to produce new derivatives that are more water soluble.
      Here, the enzymatic glycosylation of avermectin was catalyzed by uridine
      diphosphate (UDP)-glycosyltransferase from Bacillus licheniformis with various
      UDP sugars. As a result, the following four avermectin B1a glycosides were
      produced: avermectin B1a 4"-beta-D-glucoside, avermectin B1a 4"-beta-D
      galactoside, avermectin B1a 4"-beta-L-fucoside, and avermectin B1a 4"-beta-2
      deoxy-D-glucoside. The avermectin B1a glycosides were structurally analyzed based
      on HR-ESI MS and 1D and 2D nuclear magnetic resonance spectra, and the anti
      nematodal effect of avermectin B1a 4"-beta-D-glucoside was found to exhibit the
      highest activity (IC50 = 0.23 MUM), which was approximately 32 times greater than
      that of avermectin B1a (IC50 = 7.30 MUM), followed by avermectin B1a 4"-beta-2
      deoxy-D-glucoside (IC50 = 0.69 MUM), avermectin B1a 4"-beta-L-fucoside (IC50 =
      0.89 MUM), and avermectin B1a 4"-beta-D-galactoside (IC50 = 1.07 MUM). These
      results show that glycosylation of avermectin B1a effectively enhances its in
      vitro anti-nematodal activity and that avermectin glycosides can be further
      applied for treating infestations of the pine wood nematode B. xylophilus.

PMID- 29372300
TI  - The antibacterial activity of LI-F type peptide against methicillin-resistant
      Staphylococcus aureus (MRSA) in vitro and inhibition of infections in murine
      scalded epidermis.
AB  - LI-F type peptides are a family of cyclic lipodepsipeptide antibiotics isolated
      from Paenibacillus polymyxa and display potent activities against positive
      bacteria including methicillin-resistant S. aureus (MRSA). In this study, we
      investigated the mechanism of action of LI-F type peptide AMP-jsa9 against a MRSA
      (S. aureus CICC10790), which is resistant to ciprofloxacin, gentamicin,
      kanamycin, chloramphenicol, methicillin, and tetracycline. It was found that AMP
      jsa9 mainly targets the cell membrane of MRSA and is able to inhibit biofilm
      formation through killing planktonic bacteria cells. Moreover, AMP-jsa9 can bind
      to DNA in vitro, which represents another pathway for the action on MRSA.
      Furthermore, in vivo treatment of scalded mice with AMP-jsa9 resulted in
      inhibiting MRSA infections and healing of the scalded wound. In addition, it was
      demonstrated that AMP-jsa9 can effectively inhibit MRSA infections in scalded
      murine epidermis and that inflammatory cytokines including IL-8, IL-6, tumor
      necrosis factor alpha (TNF-alpha), and monocyte chemotactic factor-1 (MCP-1) were
      reduced; moreover, both protein and gene expression levels of vascular
      endothelial growth factor (VEGF) and endothelial nitric oxide synthase (e-NOS)
      were enhanced, which promote neovascularization and proliferation of new
      granulation tissue.

PMID- 29372303
TI  - [Comparison of two optical biometric devices for intraocular lens calculation].
AB  - BACKGROUND: Modern cataract surgery not only consists of a minimally invasive
      lens extraction but also of the implantation of a suitable intraocular lens.
      OBJECTIVE: The aim of this prospective trial was a comparison of the predicted
      refractive error of two optical biometers, the IOLMaster 500 and LenStar LS 900
      for intraocular lens power calculation in cataract surgery. MATERIAL AND METHODS:
      This was a prospective, analytical, comparative, non-masked study. A total of 86
      eyes of 86 patients were examined and measured with both instruments before and
      after uneventful cataract surgery. Primary outcome measures were the differences
      of the predicted refractive error of both instruments. The predicted refractive
      error was calculated with different formulas. The results were compared to each
      other, to the desired target refraction as well as to the postoperative spherical
      equivalent. RESULTS: The mean differences in predicted refractive error of both
      instruments varied between 0.9 +/- 0.19 (standard deviation) diopters (D) and
      0.18 +/- 0.30 D depending on the chosen formula. The IOLMaster 500 predicted less
      difference to the desired target refraction as well as to the spherical
      equivalent than the LenStar LS 900 with nearly all formulas. CONCLUSION: Both
      devices generated reproducible exact data with only a small deviation from the
      desired target refraction and from the postoperative spherical equivalent. There
      were statistically significant differences based on the chosen a-constants as
      well as the utilized measurement methods of both instruments.

PMID- 29372301
TI  - Effect of variations in dietary Pi intake on intestinal Pi transporters (NaPi
      IIb, PiT-1, and PiT-2) and phosphate-regulating factors (PTH, FGF-23, and MEPE).
AB  - Hyperphosphatemia is a common condition in patients with chronic kidney disease
      (CKD) and can lead to bone disease, vascular calcification, and increased risks
      of cardiovascular disease and mortality. Inorganic phosphate (Pi) is absorbed in
      the intestine, an important step in the maintenance of homeostasis. In CKD, it is
      not clear to what extent Pi absorption is modulated by dietary Pi. Thus, we
      investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations
      in dietary Pi concentration over 2 days would alter hormones involved in Pi
      metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the
      expression of matrix extracellular phosphoglycoprotein (MEPE) in different
      segments of the small intestine. The animals were divided into groups receiving
      different levels of dietary phosphate: low (Nx/LPi), normal (Nx/NPi), and high
      (Nx/HPi). Serum phosphate, fractional excretion of phosphate, intact serum
      fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were
      significantly higher and ionized calcium was significantly lower in the Nx/HPi
      group than in the Nx/LPi group. The expression levels of NaPi-IIb and PiT-1/2
      were increased in the total jejunum mucosa of the Nx/LPi group compared with the
      Nx/HPi group. Modification of Pi concentration in the diet affected the apoptosis
      of enterocytes, particularly with Pi overload. MEPE expression was higher in the
      Nx/HPi group than in the Nx/NPi. These data reveal the importance of early
      control of Pi in uremia to prevent an increase in serum PTH and FGF-23. Uremia
      may be a determining factor that explains the expressional modulation of the
      cotransporters in the small intestine segments.

PMID- 29372304
TI  - Multiple reward-cue contingencies favor expectancy over uncertainty in shaping
      the reward-cue attentional salience.
AB  - Reward-predicting cues attract attention because of their motivational value. A
      debated question regards the conditions under which the cue's attentional
      salience is governed more by reward expectancy rather than by reward uncertainty.
      To help shedding light on this relevant issue, here, we manipulated expectancy
      and uncertainty using three levels of reward-cue contingency, so that, for
      example, a high level of reward expectancy (p = .8) was compared with the highest
      level of reward uncertainty (p = .5). In Experiment 1, the best reward-cue during
      conditioning was preferentially attended in a subsequent visual search task. This
      result was replicated in Experiment 2, in which the cues were matched in terms of
      response history. In Experiment 3, we implemented a hybrid procedure consisting
      of two phases: an omission contingency procedure during conditioning, followed by
      a visual search task as in the previous experiments. Crucially, during both
      phases, the reward-cues were never task relevant. Results confirmed that, when
      multiple reward-cue contingencies are explored by a human observer, expectancy is
      the major factor controlling both the attentional and the oculomotor salience of
      the reward-cue.

PMID- 29372302
TI  - Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic
      uremic syndrome (HUS).
AB  - Hemolytic uremic syndrome (HUS) is defined as a triad of noninmune
      microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The
      most frequent presentation is secondary to Shiga toxin (Stx)-producing
      Escherichia coli (STEC) infections, which is termed postdiarrheal, epidemiologic
      or Stx-HUS, considering that Stx is the necessary etiological factor. After
      ingestion, STEC colonize the intestine and produce Stx, which translocates across
      the intestinal epithelium. Once Stx enters the bloodstream, it interacts with
      renal endothelial and epithelial cells, and leukocytes. This review summarizes
      the current evidence about the involvement of inflammatory components as central
      pathogenic factors that could determine outcome of STEC infections. Intestinal
      inflammation may favor epithelial leakage and subsequent passage of Stx to the
      systemic circulation. Vascular damage triggered by Stx promotes not only release
      of thrombin and increased fibrin concentration but also production of cytokines
      and chemokines by endothelial cells. Recent evidence from animal models and
      patients strongly indicate that several immune cells types may participate in HUS
      physiopathology: neutrophils, through release of proteases and reactive oxygen
      species (ROS); monocytes/macrophages through secretion of cytokines and
      chemokines. In addition, high levels of Bb factor and soluble C5b-9 (sC5b-9) in
      plasma as well as complement factors adhered to platelet-leukocyte complexes,
      microparticles and microvesicles, suggest activation of the alternative pathway
      of complement. Thus, acute immune response secondary to STEC infection, the Stx
      stimulatory effect on different immune cells, and inflammatory stimulus secondary
      to endothelial damage all together converge to define a strong inflammatory
      status that worsens Stx toxicity and disease.

PMID- 29372305
TI  - Genomic diversity and population structure of three autochthonous Greek sheep
      breeds assessed with genome-wide DNA arrays.
AB  - In the present study, genome-wide genotyping was applied to characterize the
      genetic diversity and population structure of three autochthonous Greek breeds:
      Boutsko, Karagouniko and Chios. Dairy sheep are among the most significant
      livestock species in Greece numbering approximately 9 million animals which are
      characterized by large phenotypic variation and reared under various farming
      systems. A total of 96 animals were genotyped with the Illumina's OvineSNP50K
      microarray beadchip, to study the population structure of the breeds and develop
      a specialized panel of single-nucleotide polymorphisms (SNPs), which could
      distinguish one breed from the others. Quality control on the dataset resulted in
      46,125 SNPs, which were used to evaluate the genetic structure of the breeds.
      Population structure was assessed through principal component analysis (PCA) and
      admixture analysis, whereas inbreeding was estimated based on runs of
      homozygosity (ROHs) coefficients, genomic relationship matrix inbreeding
      coefficients (FGRM) and patterns of linkage disequilibrium (LD). Associations
      between SNPs and breeds were analyzed with different inheritance models, to
      identify SNPs that distinguish among the breeds. Results showed high levels of
      genetic heterogeneity in the three breeds. Genetic distances among breeds were
      modest, despite their different ancestries. Chios and Karagouniko breeds were
      more genetically related to each other compared to Boutsko. Analysis revealed
      3802 candidate SNPs that can be used to identify two-breed crosses and purebred
      animals. The present study provides, for the first time, data on the genetic
      background of three Greek indigenous dairy sheep breeds as well as a specialized
      marker panel that can be applied for traceability purposes as well as targeted
      genetic improvement schemes and conservation programs.

PMID- 29372306
TI  - [Updates on tumours of the salivary glands : 2017 WHO classification].
AB  - In the new 2017 WHO classification, a reduction of the high number of entities of
      salivary carcinomas was implemented. There is only one new carcinoma entity:
      secretory carcinoma. There is a slight increase of reactive and benign entities
      by the inclusion of rare and well-established, but so far not included, lesions.
      Furthermore, there are some conceptual changes and pure changes in terminology.
      The impact of molecular findings is increasing and is so far restricted to
      diagnostic aspects.

PMID- 29372307
TI  - [Proposal for an extended pTNM classification of thyroid carcinoma : Commentary
      on deficits of the 8th edition of the TNM classification (German version)].
AB  - In the 8th edition of the TNM classification of thyroid carcinomas, which was
      introduced in 2017, carcinomas with minimal extrathyroidal extension are no
      longer mentioned, which might cause problems. These tumors were explicitly
      categorized in previous TNM classifications (5-7th editions). Studies on the
      prognostic relevance of minimal extrathyroidal extension have shown conflicting
      results. Moreover, the vast majority of these studies retrospectively analyzed
      only subgroups of thyroid carcinomas (e.g. differentiated thyroid carcinoma,
      papillary thyroid carcinoma). The proposed subcategorization of the current TNM
      classification (8th edition) ensures the continuity of the parameter minimal
      extrathyroidal extension within the TNM categorization of thyroid carcinomas and
      also offers the possibility to prospectively analyze in a standardized manner the
      potential biological relevance of minimal extrathyroidal extension in relation to
      tumor categories (T/pT category).

PMID- 29372308
TI  - Internal tandem duplication mutations in the tyrosine kinase domain of FLT3
      display a higher oncogenic potential than the activation loop D835Y mutation.
AB  - Acute myeloid leukemia (AML) remains the most common form of acute leukemia among
      adults and accounts for a large number of leukemia-related deaths. Mutations in
      FMS-like tyrosine kinase 3 (FLT3) is one of the most prevalent findings in this
      heterogeneous disease. The major types of mutations in FLT3 can be categorized as
      internal tandem duplications (ITD) and point mutations. Recent studies suggest
      that ITDs not only occur in the juxtamembrane region as originally described, but
      also in the kinase domain. Although the juxtamembrane ITDs have been well
      characterized, the tyrosine kinase domain ITDs have not yet been thoroughly
      studied due to their recent discovery. For this reason, we compared ITD mutations
      in the juxtamembrane domain with those in the tyrosine kinase domain, as well as
      with the most common activating point mutation in the tyrosine kinase domain,
      D835Y. The purpose of this study was to understand whether it is the nature of
      the mutation or the location of the mutation that plays the main role in
      leukemogenesis. The various FLT3 mutants were expressed in the murine pro-B cell
      line Ba/F3 and examined for their capacity to form colonies in semisolid medium.
      The size and number of colonies formed by Ba/F3 cells expressing either the
      internal tandem duplication within juxtamembrane domain of the receptor (JMD-ITD)
      or the tyrosine kinase domain (TKD)-ITD were indistinguishable, while Ba/F3 cells
      expressing D835Y/FLT3 failed to form colonies. Cell proliferation and cell
      survival was also significantly higher in TKD-ITD expressing cells, compared to
      cells expressing D835Y/FLT3. Furthermore, TKD-ITD is capable of inducing
      phosphorylation of STAT5, while D835Y/FLT3 fails to induce tyrosine
      phosphorylation of STAT5. Other signal transduction pathways such as the RAS/ERK
      and the PI3K/AKT pathways were activated to the same level in TKD-ITD cells as
      compared to D835Y/FLT3 expressing cells. Taken together, our data suggest that
      TKD-ITD displays similar oncogenic potential to the JMD-ITD but a higher
      oncogenic potential than the D835Y point mutation.

PMID- 29372310
TI  - Potential of delphinidin-3-rutinoside extracted from Solanum melongena L. as
      promoter of osteoblastic MC3T3-E1 function and antagonist of oxidative damage.
AB  - PURPOSE: Increasing evidence suggests the potential use of natural antioxidant
      compounds in the prevention/treatment of osteoporosis. This study was undertaken
      to investigate the effects of purified delphinidin-3-rutinoside (D3R), isolated
      from Solanum melongena L., on osteoblast viability and differentiation in basal
      conditions and its ability to protect MC3T3-E1 cells against oxidative damage
      induced by tert-butyl hydroperoxide (t-BHP). METHODS: MC3T3-E1 osteoblastic cells
      were treated with D3R (10-11-10-5 M for 24 h), followed by treatment with t-BHP
      (250 uM for 3 h). To test cell viability, MTT test was performed. Apoptotic cells
      were stained with Hoechst-33258 dye. Cytoskeleton rearrangement was stained with
      FICT-labelled phalloidin. Intracellular ROS production was measured using
      dichlorofluorescein CM-DCFA. The reduced glutathione to oxidized glutathione
      ratio (GSH/GSSG) contents was measured according to the OPT fluorimetric assay.
      RESULTS: D3R (10-9 M) significantly increases viability of MC3T3-E1 cells and
      promotes osteoblast differentiation by increasing the expression of type I
      collagen, alkaline phosphatase and osteocalcin. Pre-treatment with D3R (10-9 M)
      significantly prevented t-BHP-induced osteoblastic dysfunction and changes in the
      cytoskeleton organization by decreasing intracellular ROS and preventing the
      reduction in GSH/GSSG. D3R did not significantly modify the expression of
      Osteoprotegerin/RANKL system activated by t-BHP suggesting a lack of effect of
      D3R on osteoblast/osteoclast crosstalk. D3R protective effects against t-BHP
      induced osteoblastic dysfunction were mediated by the PI3K/Akt pathway since they
      were completely prevented by LY294002, a PI3K/Akt specific inhibitor.
      CONCLUSIONS: These findings indicate that D3R protects MC3T3-E1 cells from
      oxidative damage and suggest the potential utility of dietary D3R supplement to
      prevent osteoblast dysfunction in age-related osteoporosis.

PMID- 29372309
TI  - More sex chromosomes than autosomes in the Amazonian frog Leptodactylus
      pentadactylus.
AB  - Heteromorphic sex chromosomes are common in eukaryotes and largely ubiquitous in
      birds and mammals. The largest number of multiple sex chromosomes in vertebrates
      known today is found in the monotreme platypus (Ornithorhynchus anatinus, 2n =
      52) which exhibits precisely 10 sex chromosomes. Interestingly, fish, amphibians,
      and reptiles have sex determination mechanisms that do or do not involve
      morphologically differentiated sex chromosomes. Relatively few amphibian species
      carry heteromorphic sex chromosomes, and when present, they are frequently
      represented by only one pair, either XX:XY or ZZ:ZW types. Here, in contrast,
      with several evidences, from classical and molecular cytogenetic analyses, we
      found 12 sex chromosomes in a Brazilian population of the smoky jungle frog,
      designated as Leptodactylus pentadactylus Laurenti, 1768 (Leptodactylinae), which
      has a karyotype with 2n = 22 chromosomes. Males exhibited an astonishing stable
      ring-shaped meiotic chain composed of six X and six Y chromosomes. The number of
      sex chromosomes is larger than the number of autosomes found, and these data
      represent the largest number of multiple sex chromosomes ever found among
      vertebrate species. Additionally, sequence and karyotype variation data suggest
      that this species may represent a complex of species, in which the chromosomal
      rearrangements may possibly have played an important role in the evolution
      process.

PMID- 29372311
TI  - Association between sugar-sweetened beverage consumption and incident
      hypertension in Korean adults: a prospective study.
AB  - PURPOSE: Epidemiological information on the association between sugar-sweetened
      beverage (SSB) consumption and the risk for hypertension (HTN) in Koreans is very
      limited. We tested the hypothesis that increased SSB consumption is related to a
      higher risk of HTN among middle-aged Korean adults in a Korean community-based
      cohort. METHODS: From participants of the cohort from 2001 to 2010, we selected
      5775 subjects without HTN, diabetes, cardiovascular disease, and cancer and who
      had no information on dietary assessment at baseline. To assess the relationship
      between SSB consumption and HTN, we estimated hazard ratios (HRs) and 95%
      confidence intervals using Cox regression analysis. In addition, stratified
      analysis by body mass index (BMI) was conducted. RESULTS: During the follow-up,
      we identified 1175 cases of incident HTN. The adjusted HR of HTN for the highest
      quartile of SSB consumption was 1.21 compared to the lowest quartile.
      Furthermore, higher consumption of SSB was significantly associated with
      increased incidence of HTN in subjects with BMI >= 25 kg/m2, whereas there was no
      significant association among subjects with BMI < 25 kg/m2. CONCLUSIONS: The
      results of this study suggest that SSB consumption was associated with an
      increased risk of HTN, particularly among obese participants.

PMID- 29372312
TI  - Benefit of 18F-fluorocholine PET imaging in parathyroid surgery.
AB  - OBJECTIVES: To assess the additional diagnostic value of 18F-fluorocholine PET
      imaging in preoperative localization of pathologic parathyroid glands in
      clinically manifest hyperparathyroidism in case of negative or conflicting
      ultrasound and scintigraphy results. METHODS: A retrospective, single-institution
      study of 26 patients diagnosed with hyperparathyroidism. In cases where
      ultrasound and scintigraphy failed to detect the location of an adenoma in order
      to allow a focused surgical approach, an additional 18F-fluorocholine PET scan
      was performed and its results were compared with the intraoperative findings.
      RESULTS: A total of 26 patients underwent 18F-fluorocholine PET/CT (n = 11) or
      PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients
      underwent surgery, and the location predicted by PET hybrid imaging was confirmed
      intraoperatively by frozen section and adequate parathyroid hormone drop after
      removal. None of the patients needed revision surgery during follow-up.
      CONCLUSIONS: These results demonstrate that 18F-fluorocholine PET imaging is a
      highly accurate method to detect parathyroid adenomas even in case of previous
      localization failure by other imaging examinations. KEY POINTS: * With 18 F
      fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. * 18
      F-fluorocholine imaging is a highly accurate method to detect parathyroid
      adenomas. * We encourage its use, where ultrasound fails to detect an adenoma.

PMID- 29372313
TI  - Immersive virtual reality-based training improves response in a simulated
      operating room fire scenario.
AB  - BACKGROUND: SAGES FUSE curriculum provides didactic knowledge on OR fire
      prevention. The objective of this study is to evaluate the impact of an immersive
      virtual reality (VR)-based OR fire training simulation system in combination with
      FUSE didactics. METHODS: The study compared a control with a simulation group.
      After a pre-test questionnaire that assessed the baseline knowledge, both groups
      were given didactic material that consists of a 10-min presentation and reading
      materials about precautions and stopping an OR fire from the FUSE manual. The
      simulation group practiced on the OR fire simulation for one session that
      consisted of five trials within a week from the pre-test. One week later, both
      groups were reassessed using a questionnaire. A week after the post-test both
      groups also participated in a simulated OR fire scenario while their performance
      was videotaped for assessment. RESULTS: A total of 20 subjects (ten per group)
      participated in this IRB approved study. Median test scores for the control group
      increased from 5.5 to 9.00 (p = 0.011) and for the simulation group it increased
      from 5.0 to 8.5 (p = 0.005). Both groups started at the same baseline (pre-test,
      p = 0.529) and reached similar level in cognitive knowledge (post-test, p =
      0.853). However, when tested in the mock OR fire scenario, 70% of the simulation
      group subjects were able to perform the correct sequence of steps in
      extinguishing the simulated fire whereas only 20% subjects in the control group
      were able to do so (p = 0.003). The simulation group was better than control
      group in correctly identifying the oxidizer (p = 0.03) and ignition source (p =
      0.014). CONCLUSIONS: Interactive VR-based hands-on training was found to be a
      relatively inexpensive and effective mode for teaching OR fire prevention and
      management scenarios.

PMID- 29372315
TI  - Predicting the ergogenic response to methylphenidate.
AB  - PURPOSE: Methylphenidate (MPH) and other stimulants have been shown to enhance
      physical performance. However, stimulant research has almost exclusively been
      conducted in young, active persons with a normal BMI, and may not generalize to
      other groups. The purpose of this study was to determine whether the ergogenic
      response to MPH could be predicted by individual level characteristics. METHODS:
      We investigated whether weekly minutes of moderate-to-vigorous physical activity
      (MVPA), age, and BMI could predict the ergogenic response to MPH. In a double
      blind, cross-over design 29 subjects (14M, 15F, 29.7 +/- 9.68 years, BMI: 26.1 +/
      6.82, MVPA: 568.8 +/- 705.6 min) ingested MPH or placebo before performing a
      handgrip task. Percent change in mean force between placebo and MPH conditions
      was used to evaluate the extent of the ergogenic response. RESULTS: Mean force
      was significantly higher in MPH conditions [6.39% increase, T(25) = 3.09, p =
      0.005 118.8 +/- 37.96 (+/- SD) vs. 111.8 +/- 34.99 Ns] but variable (coefficient
      of variation:163%). Using linear regression, we observed that min MVPA (T(25) = 
      2.15, beta = -0.400, p = 0.044) and age [T(25) = -3.29, beta = -0.598, p = 0.003]
      but not BMI [T(25) = 1.67, beta = 0.320 p = 0.109] significantly predicted
      percent change in mean force in MPH conditions. CONCLUSIONS: We report that lower
      levels of physical activity and younger age predict an improved ergogenic
      response to MPH and that this may be explained by differences in dopaminergic
      function. This study illustrates that the ergogenic response to MPH is partly
      dependent on individual differences such as habitual levels of physical activity
      and age.

PMID- 29372314
TI  - Adaptive servo-ventilation and sleep quality in treatment emergent central sleep
      apnea and central sleep apnea in patients with heart disease and preserved
      ejection fraction.
AB  - BACKGROUND: Reduced sleep quality is associated with impaired quality of life and
      increased mortality in patients with heart failure. The aim of this study was to
      observe changes in sleep fragmentation and sleep quality in patients with heart
      disease and preserved left ventricular ejection fraction (pEF) treated with
      adaptive servo-ventilation (ASV) therapy for treatment of emergent central sleep
      apnea (TECSA) or central sleep apnea (CSA). METHODS: 114 patients with structural
      heart disease and pEF introduced to ASV therapy between 2010 and 2015 were
      retrospectively analyzed. Patients were stratified into two groups; TECSA (n =
      60) or CSA (n = 54). Changes of sleep fragmentation and sleep quality from
      baseline to ASV initiation were compared. RESULTS: ASV therapy leads to a
      significant reduction of apnea-hypopnea index (AHI) and arousal index in patients
      with TECSA and CSA (?AHI: - 43 +/- 21 vs. - 47 +/- 22/h; ?arousal index - 11 +/-
      15, vs. - 11 +/- 21/h). ASV treatment leads to a significant increase in sleep
      efficiency in TECSA compared to CSA (?SE: 10 +/- 19 vs. 1 +/- 18%, p = 0.019).
      Both groups had significantly longer stage N3 (N3) and rapid eye movement sleep
      (REM) on ASV (?N3: 8 +/- 11 vs. 9 +/- 13%; ?REM 7 +/- 9 vs. 3 +/- 8%; p < 0.05
      for all comparisons baseline vs. ASV). CONCLUSIONS: In patients with heart
      disease and pEF, whose TECSA and CSA were treated with ASV, a significant
      reduction of AHI and arousal index as well as an increase of N3 and REM sleep was
      observed. Increase of sleep efficiency was significantly greater in TECSA
      compared to CSA. Hence, improvements of sleep quality were modestly greater in
      patients with TECSA compared to those with CSA.

PMID- 29372316
TI  - DAWN: Another Boost for Endovascular Thrombectomy in Patients with Acute Ischemic
      Stroke.

PMID- 29372318
TI  - cIMPACT-NOW update 1: Not Otherwise Specified (NOS) and Not Elsewhere Classified
      (NEC).

PMID- 29372319
TI  - Molecular detection of Oxyspirura larvae in arthropod intermediate hosts.
AB  - To determine potential intermediate hosts of Oxyspirura petrowi, a common
      nematode eyeworm of wild gallinaceous birds, various arthropod species including
      red harvester ants, beetles, wood cockroaches, crickets, grasshoppers, katydids,
      and desert termites were screened for the presence of O. petrowi using specific
      polymerase chain reaction (PCR) primers targeting the internal transcribed spacer
      2 region (ITS2) of the eyeworm ribosomal deoxyribonucleic acid (rDNA). This is
      the first study to investigate the intermediate hosts of O. petrowi utilizing
      molecular techniques. We determined 38% (13/34) of the cockroaches, 27% (3/11) of
      the crickets, and 23% (68/289) of the grasshoppers which were positive for O.
      petrowi. Identifying potential intermediate hosts of O. petrowi is essential to
      better understanding the epizoology of the eyeworm's transmission mechanics and
      to controlling infections in wild gallinaceous birds.

PMID- 29372320
TI  - Advances in cardiac cellular electrophysiology - Relevance for clinical
      translation.

PMID- 29372317
TI  - The genetic architecture of mitochondrial dysfunction in Parkinson's disease.
AB  - Mitochondrial impairment is a well-established pathological pathway implicated in
      Parkinson's disease (PD). Defects of the complex I of the mitochondrial
      respiratory chain have been found in post-mortem brains from sporadic PD
      patients. Furthermore, several disease-related genes are linked to mitochondrial
      pathways, such as PRKN, PINK1, DJ-1 and HTRA2 and are associated with
      mitochondrial impairment. This phenotype can be caused by the dysfunction of
      mitochondrial quality control machinery at different levels: molecular,
      organellar or cellular. Mitochondrial unfolded protein response represents the
      molecular level and implicates various chaperones and proteases. If the molecular
      level of quality control is not sufficient, the organellar level is required and
      involves mitophagy and mitochondrial-derived vesicles to sequester whole
      dysfunctional organelle or parts of it. Only when the impairment is too severe,
      does it lead to cell death via apoptosis, which defines the cellular level of
      quality control. Here, we review how currently known PD-linked genetic variants
      interfere with different levels of mitochondrial quality control. We discuss the
      graded risk concept of the most recently identified PARK loci (PARK 17-23) and
      some susceptibility variants in GBA, LRRK2 and SNCA. Finally, the emerging
      concept of rare genetic variants in candidates genes for PD, such as HSPA9, TRAP1
      and RHOT1, complete the picture of the complex genetic architecture of PD that
      will direct future precision medicine approaches.

PMID- 29372321
TI  - Correction to: Collagen degradation as a possibility to determine the post-mortem
      interval (PMI) of animal bones: a validation study referring to an original study
      of Boaks et al. (2014).
AB  - The original version of this article contains an error. The Author Katharina
      Hoeland incorrectly listed as Katharina Holand. The correct spelling is presented
      above. The original article has been corrected.

PMID- 29372322
TI  - Marker evaluation for differentiation of blood and menstrual fluid by methylation
      sensitive SNaPshot analysis.
AB  - The differentiation of blood and menstrual fluid is especially important in cases
      of alleged sexual assault. While the identification of blood is relatively
      straightforward, the identification of menstrual fluid in trace evidence has been
      shown to be more challenging. This may be due to the complex nature of menstrual
      fluid that leads to intra- and inter-individual differences in composition.
      Nevertheless, recent advances in DNA methylation profiling have revealed
      promising markers for the differentiation of the two body fluids and furthermore,
      markers to distinguish menstrual fluid from vaginal fluid. A literature study was
      performed and in total, 11 markers were evaluated in this study of which seven
      could be validated for menstrual fluid and blood identification purposes. Marker
      "BLU2" (chr16:29757334) was identified as most suitable for differentiation of
      blood and menstrual fluid.

PMID- 29372323
TI  - Correction to: Dentate granule progenitor cell properties are rapidly altered
      soon after birth.
AB  - In the original publication figure parts 8c, 8f, and 8i were mixed up and thus
      incorrectly labeled. Here is a corrected version with the parts properly labeled.

PMID- 29372325
TI  - Grey matter structural differences in alcohol-dependent individuals with and
      without comorbid depression/anxiety-an MRI study.
AB  - Although depression and anxiety disorders are common comorbid conditions in
      alcohol dependence, few structural brain imaging studies have compared alcohol
      dependent subjects with and without such comorbidity. In the current study, brain
      scans of 35 alcohol-dependent with and 40 individuals without diagnosis of a
      comorbid ICD-10 depressive or anxiety disorder receiving detoxification inpatient
      treatment were evaluated. Thickness and volumes of automatically segmented
      neuroanatomical structures were measured in FreeSurfer. Furthermore, associations
      of brain structure with biological markers and clinical severity markers of
      alcohol dependence were assessed. Despite comparable addiction severity, the non
      comorbid group had evidence of higher cytotoxic effects of alcohol use on hepatic
      and haematological markers, and showed significantly smaller volumes of total
      cerebral, and cerebellar grey matter. Similarly, they showed unexpected smaller
      hippocampal and nucleus accumbens volumes, and thinner frontal, temporal and
      occipital cortices. Smaller brain volumes correlated with increased markers of
      hepatic and haematological dysfunction, and with longer duration of alcohol
      dependence in the non-comorbid group. Evidence of higher biomarkers of alcohol
      use may be indicative of more severe alcohol dependence or higher vulnerability
      to ethanol toxicity in this group. Furthermore, psychopathology-related drug
      treatment, which occurred in 53% of the comorbid group over the recent years, or
      tissue inflammation may have a moderate effect on the grade of cerebral atrophy
      in alcohol-dependent patients. Longitudinal studies are needed to investigate
      this issue more fully.

PMID- 29372324
TI  - Transient and localized optogenetic activation of somatostatin-interneurons in
      mouse visual cortex abolishes long-term cortical plasticity due to vision loss.
AB  - Unilateral vision loss through monocular enucleation (ME) results in partial
      reallocation of visual cortical territory to another sense in adult mice. The
      functional recovery of the visual cortex occurs through a combination of spared
      eye potentiation and cross-modal reactivation driven by whisker-related,
      somatosensory inputs. Brain region-specific intracortical inhibition was recently
      recognized as a crucial regulator of the cross-modal component, yet the
      contribution of specific inhibitory neuron subpopulations remains poorly
      understood. Somatostatin (SST)-interneurons are ideally located within the
      cortical circuit to modulate sensory integration. Here we demonstrate that
      optogenetic stimulation of visual cortex SST-interneurons prior to eye removal
      decreases ME-induced cross-modal recovery at the stimulation site. Our results
      suggest that SST-interneurons act as local hubs, which are able to control the
      influx and extent of cortical cross-modal inputs into the deprived cortex. These
      insights critically expand our understanding of SST-interneuron-specific
      regulation of cortical plasticity induced by sensory loss.

PMID- 29372326
TI  - Molecular modeling of immersion optical clearing of biological tissues.
AB  - The interaction of six low-molecular tissue-clearing agents (1,2 and 1,3
      propanediol, ethylene glycol, glycerol, xylitol, sorbitol) with the collagen
      mimetic peptide (GPH)3 was studied by applying the methods of classical molecular
      dynamics (GROMACS), molecular docking (AutoDock Vina) and quantum chemistry (PM6
      and B3LYP). The spatial configurations of intermolecular complexes were
      determined and interaction energies calculated. The dependence of the volume
      occupied by the collagen peptide on the clearing agent concentration in an
      aqueous solution was calculated. This dependence is not linear, and has a maximum
      for almost all the agents in the study. The correlations between the optical
      clearing potential and intermolecular interactions parameters, such as the time
      of an agent being in a hydrogen-bonded state, and the relative probability of
      formation of double hydrogen bonds and interaction energies, were determined.
      Using the correlations determined, we predicted the numeric value of the optical
      clearing potential of dextrose molecules in rat skin, which correlates with
      experimental data. A molecular mechanism of tissue optical clearing within the
      post-diffusion stage is suggested. Graphical abstract The molecular modeling of
      the interaction between clearing agents and collagen.

PMID- 29372327
TI  - Content Based Image Retrieval by Using Color Descriptor and Discrete Wavelet
      Transform.
AB  - Due to recent development in technology, the complexity of multimedia is
      significantly increased and the retrieval of similar multimedia content is a open
      research problem. Content-Based Image Retrieval (CBIR) is a process that provides
      a framework for image search and low-level visual features are commonly used to
      retrieve the images from the image database. The basic requirement in any image
      retrieval process is to sort the images with a close similarity in term of
      visually appearance. The color, shape and texture are the examples of low-level
      image features. The feature plays a significant role in image processing. The
      powerful representation of an image is known as feature vector and feature
      extraction techniques are applied to get features that will be useful in
      classifying and recognition of images. As features define the behavior of an
      image, they show its place in terms of storage taken, efficiency in
      classification and obviously in time consumption also. In this paper, we are
      going to discuss various types of features, feature extraction techniques and
      explaining in what scenario, which features extraction technique will be better.
      The effectiveness of the CBIR approach is fundamentally based on feature
      extraction. In image processing errands like object recognition and image
      retrieval feature descriptor is an immense among the most essential step. The
      main idea of CBIR is that it can search related images to an image passed as
      query from a dataset got by using distance metrics. The proposed method is
      explained for image retrieval constructed on YCbCr color with canny edge
      histogram and discrete wavelet transform. The combination of edge of histogram
      and discrete wavelet transform increase the performance of image retrieval
      framework for content based search. The execution of different wavelets is
      additionally contrasted with discover the suitability of specific wavelet work
      for image retrieval. The proposed algorithm is prepared and tried to implement
      for Wang image database. For Image Retrieval Purpose, Artificial Neural Networks
      (ANN) is used and applied on standard dataset in CBIR domain. The execution of
      the recommended descriptors is assessed by computing both Precision and Recall
      values and compared with different other proposed methods with demonstrate the
      predominance of our method. The efficiency and effectiveness of the proposed
      approach outperforms the existing research in term of average precision and
      recall values.

PMID- 29372329
TI  - Gaseous Signaling Molecules in Cardiovascular Function: From Mechanisms to
      Clinical Translation.
AB  - Carbon monoxide (CO), hydrogen sulfide (H2S), and nitric oxide (NO) constitute
      endogenous gaseous molecules produced by specific enzymes. These gases are
      chemically simple, but exert multiple effects and act through shared molecular
      targets to control both physiology and pathophysiology in the cardiovascular
      system (CVS). The gases act via direct and/or indirect interactions with each
      other in proteins such as heme-containing enzymes, the mitochondrial respiratory
      complex, and ion channels, among others. Studies of the major impacts of CO, H2S,
      and NO on the CVS have revealed their involvement in controlling blood pressure
      and in reducing cardiac reperfusion injuries, although their functional roles are
      not limited to these conditions. In this review, the basic aspects of CO, H2S,
      and NO, including their production and effects on enzymes, mitochondrial
      respiration and biogenesis, and ion channels are briefly addressed to provide
      insight into their biology with respect to the CVS. Finally, potential
      therapeutic applications of CO, H2S, and NO with the CVS are addressed, based on
      the use of exogenous donors and different types of delivery systems.

PMID- 29372328
TI  - Review and clinical presentation in reverse shoulder arthroplasty in deltoid
      palsy.
AB  - Deltoid palsy is a classical contraindication for reverse shoulder arthroplasty
      (RSA). However, in cases associating axillary nerve palsy and rotator cuff tear
      or glenohumeral arthritis, few options remain. We present a case in which
      combining RSA with transfer of the pectoralis major and upper and middle
      trapezius transfer provided satisfactory results in a patient suffering of both
      an irreparable rotator cuff tear and a deltoid palsy.Level of evidence IV.

PMID- 29372330
TI  - Pre-incubation in soil improves the nitrogen fertiliser value of hair waste.
AB  - Global generation of human hair waste and its disposal at landfills could
      contribute to the leaching of nitrates into ground water. High concentrations of
      nitrogen (N) and other elements suggest that the waste could be a source of plant
      nutrients and differences in ethnic hair types could affect nutrient release and
      fertiliser value. The objective of this study was to determine the effects of
      hair type, as an N source, and pre-incubation time on dry-matter yield, nutrient
      uptake by spinach (Spinacia oleracea L.) and residual soil nutrients. Salons in
      Pietermaritzburg provided bulk African and Caucasian hair waste, without
      distinguishing age, sex, health status or livelihood of the individuals. The hair
      waste was analysed for elemental composition. A pot experiment was set up under
      glasshouse conditions. The hair waste was incorporated (400 kg N ha-1) into a
      loamy oxisol and pre-incubated for 0, 28, 56 and 84 days before planting spinach.
      Potassium (K) and phosphorus (P) were corrected to the same level for all
      treatments. Spinach seedlings were then cultivated for 6 weeks. Shoot dry-matter
      and the uptake of all nutrients, except P, were increased by the pre-incubation
      of hair. African hair pre-incubated for 28 days resulted in greater dry-matter,
      N, K, Mn and S uptake than Caucasian hair. Increasing pre-incubation resulted in
      a decline in the residual soil pH and exchangeable K. The findings suggested that
      pre-incubation improves the N fertiliser value of hair and that African hair has
      greater value than Caucasian hair when pre-incubated for a short period.

PMID- 29372332
TI  - Letter from the Editor-in-Chief.

PMID- 29372331
TI  - Barriers and facilitators to parents seeking and accessing professional support
      for anxiety disorders in children: qualitative interview study.
AB  - Anxiety disorders are among the most common mental health disorders experienced
      by children, but only a minority of these children access professional help.
      Understanding the difficulties parents face seeking support for child anxiety
      disorders could inform targeted interventions to improve treatment access. The
      aims of the study were to identify barriers and facilitators to seeking and
      accessing professional support for child anxiety disorders, and ways to minimise
      these barriers. A qualitative interview study was conducted with parents of 16
      children (aged 7-11 years) with anxiety disorders identified through screening in
      schools. Barriers and facilitators were identified in relation to four distinct
      stages in the help-seeking process: parents recognising the anxiety difficulty,
      parents recognising the need for professional support, parents contacting
      professionals, and families receiving professional support. Barriers and
      facilitators at each stage related to the child's difficulties, the role of the
      parent, and parent perceptions of professionals and services. Findings illustrate
      the need (1) for readily available tools to help parents and professionals
      identify clinically significant anxiety in children, (2) to ensure that families
      and professionals can easily access guidance on the help-seeking process and
      available support, and (3) to ensure existing services offer sufficient provision
      for less severe difficulties that incorporates direct support for parents.

PMID- 29372333
TI  - PCOS and bone fractures.

PMID- 29372334
TI  - Comparison of clinical, biochemical and histomorphometric analysis of bone
      biopsies in dialysis patients with and without fractures.
AB  - Chronic kidney disease-mineral bone disorders (CKD-MBD) are associated with
      increased risk of fracture. Studies report about 3% of fractures in CKD patients,
      and these occur earlier than in the general population, namely 16 and 13 years
      earlier for men and women, respectively. Better understanding of the
      pathophysiology of fractures would probably contribute to new therapeutic
      approaches. This study aimed to evaluate report of long bone fractures from a
      bone biopsies bank from patients on hemodialysis and compare clinical and
      biochemical characteristics, as well as the results of the histomorphometric
      analysis of trabecular and cortical bone of these patients with a control group
      (without fractures), paired for age, gender, and time on hemodialysis. Bone
      proteins (SOST, DMP1 and MEPE) were evaluated by immunohistochemistry. Seventeen
      patients with fracture and controls were studied. Fracture prevalence was
      0.82/1000 patients/year. Serum phosphorus levels were significantly lower in the
      fracture group. Histomorphometric analysis revealed that all the patients had
      high turnover disease, and the fracture group had smaller volume and trabecular
      thickness, greater osteoid surface, smaller eroded surface, smaller mineralizing
      surface, formation rate and longer mineralization lag time when compared to
      controls; the DMP1 expression in the cortical bone was smaller and the SOST in
      the trabecular bone was higher in fractured patients. As conclusion, we found low
      prevalence of fractures. Both groups had high turnover disease, but the fractured
      ones presented more impaired bone microarchitecture, as well as lower formation
      and greater mineralization defect. Bone proteins expression correlated with
      parameters involved in bone remodeling.

PMID- 29372335
TI  - Higher serum uric acid is associated with higher lumbar spine bone mineral
      density in male health-screening examinees: a cross-sectional study.
AB  - Bone health has been associated with oxidative stress and antioxidants have
      received interest to this end. Serum uric acid (SUA), an end product of purine
      metabolism in humans, has recently shown antioxidant properties regarding bone
      health, but there are conflicting results. The aim of this study was to
      investigate the relationship between SUA levels and lumbar spine bone mineral
      density (BMD) in clinically apparently healthy males aged 40-60 years. We
      performed a cross-sectional study of 6588 Korean males who completed a health
      screening program from January 2011 to December 2014. Of the study participants,
      the mean age was 48.2 +/- 10.7 years. Multiple regression analyses resulted in a
      significant positive association with lumbar spine BMD across SUA quintiles in a
      dose-response manner after adjusting for various confounding factors (p = 0.013);
      for each 1 mg/dl increase of SUA, BMD rose by 0.0054 g/cm2 (p = 0.004).
      Stratified analyses revealed that this association between SUA and lumbar spine
      BMD was consistently observed across all clinically relevant subgroups. The
      present study demonstrated a positive association in males between SUA and lumbar
      spine BMD, suggesting that SUA could have a profitable effect on bone metabolism.

PMID- 29372336
TI  - High-resolution suborganellar localization of Ca2+-binding protein CAS, a novel
      regulator of CO2-concentrating mechanism.
AB  - Many aquatic algae induce a CO2-concentrating mechanism (CCM) associated with
      active inorganic carbon transport to maintain high photosynthetic affinity using
      dissolved inorganic carbon even in low-CO2 (LC) conditions. In the green alga
      Chlamydomonas reinhardtii, a Ca2+-binding protein CAS was identified as a novel
      factor regulating the expression of CCM-related proteins including bicarbonate
      transporters. Although previous studies revealed that CAS associates with the
      thylakoid membrane and changes its localization in response to CO2 and light
      availability, its detailed localization in the chloroplast has not been examined
      in vivo. In this study, high-resolution fluorescence images of CAS fused with a
      Chlamydomonas-adapted fluorescence protein, Clover, were obtained by using a
      sensitive hybrid detector and an image deconvolution method. In high-CO2 (5% v/v)
      conditions, the fluorescence signals of Clover displayed a mesh-like structure in
      the chloroplast and part of the signals discontinuously overlapped with
      chlorophyll autofluorescence. The fluorescence signals gathered inside the
      pyrenoid as a distinct wheel-like structure at 2 h after transfer to LC-light
      condition, and then localized to the center of the pyrenoid at 12 h. These
      results suggest that CAS could move in the chloroplast along the thylakoid
      membrane in response to lowering CO2 and gather inside the pyrenoid during the
      operation of the CCM.

PMID- 29372337
TI  - The roles of H2S and H2O2 in regulating AsA-GSH cycle in the leaves of wheat
      seedlings under drought stress.
AB  - This paper investigated the roles of hydrogen sulfide (H2S) and hydrogen peroxide
      (H2O2) and the possible relationship between them in regulating the AsA-GSH cycle
      in wheat leaves under drought stress (DS). Results showed that DS markedly
      increased the production of H2S and H2O2, the transcript levels and activities of
      ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate
      reductase (MDHAR), and dehydroascorbate reductase (DHAR); malondialdehyde (MDA)
      content; and electrolyte leakage (EL). Meanwhile, DS markedly reduced plant
      height and biomass. Above increases induced by drought stress except MDA content
      and EL were all suppressed by pretreatments with H2S synthesis inhibitor
      aminooxyaceticacid (AOA) and H2O2 synthesis inhibitor diphenylene iodonium (DPI).
      Besides, pretreatments with AOA and DPI further significantly increased MDA
      content and EL and significantly reduced plant height and biomass under DS. DPI
      reduced the production of H2O2 and H2S induced by DS. AOA also reduced the
      production of H2S and H2O2 induced by DS. Pretreatments with NaHS + AOA and H2O2
      + DPI reversed above effects of AOA and DPI. Our results suggested that H2S and
      H2O2 all participated in the up-regulation of AsA-GSH cycle in wheat leaves by DS
      and possibly affected each other.

PMID- 29372338
TI  - Screening for cytotoxic chemical constituents from Justicia procumbens by HPLC
      DAD-ESI-MS and NMR.
AB  - BACKGROUND: The Acanthaceae family is an important source of therapeutic drugs
      and ethno medicines. There are many famous medicinal plants from this family,
      such as Andrographis paniculata, Baphicacanthus cusia, and Dicliptera chinensis.
      Justicia procumbens (J. procumbens) is widely distributed in tropical and sub
      tropical of the world. It has long been used in traditional Chinese medicine for
      cancer. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay
      showed the ethyl acetate extract of J. procumbens had a cytotoxic activity.
      Therefore, qualitative and quantitative analysis of the chemical constituents in
      the ethyl acetate extract was important for understanding its pharmacological
      mechanism. RESULTS: A high-performance liquid chromatography with diode array
      detection coupled to electrospray ionisation quadrupole time-of-flight tandem
      mass spectrometry procedure was established. Eleven dibenzylbutanes and four
      arylnaphthalenes were confirmed by HPLC-DAD-ESI-QTOF-MS analysis. A novel
      dibenzylbutane (5-methoxy-4,4'-di-O-methylsecolariciresinol-9'-monoacetate) and
      seven isomers of arylnaphthalene were isolated and characterized by NMR and QTOF
      MS. Compounds 1, 2, and 13 were detected for the first time. The content of six
      lignans were determinated in the ethyl acetate extract. CONCLUSIONS: This study
      showed that the cytotoxic activity assay of J. procumbens could be mainly
      attributed to the constituents of lignans. The bioactivity of the ethyl acetate
      extract and determined compounds support the traditional use of this plant in
      cancer. These chemical constituents may be developed as novel therapeutics.

PMID- 29372339
TI  - Mind-Body Therapies for Late-Life Mental and Cognitive Health.
AB  - PURPOSE OF REVIEW: A growing body of research supports the use of mind-body
      therapies (MBTs) as minimally invasive and effective approaches for the
      management of late-life mood and cognitive disorders. RECENT FINDINGS: Recent
      randomized controlled trials and meta-analyses indicate that MBTs are effective
      for enhancing well-being, mood, sleep, and cognition in older adults. Evidence
      suggests that mindful movement (e.g., yoga, tai chi, walking meditation) may even
      outperform conventional physical exercise with regard to effects on quality of
      life, mood, and cognitive functioning. Practitioners may recommend MBTs as
      holistic, effective approaches for the management of common late-life mood and
      cognitive disorders. Continued research on MBTs will inform the development of
      even more effective/targeted interventions and contribute to greater acceptance
      and integration of these therapies into geriatric medicine and psychiatry.

PMID- 29372340
TI  - Bowel obstruction secondary to migration of a Ventralex mesh: report of a rare
      complication.

PMID- 29372341
TI  - Parasitic egg rejection decisions of chalk-browed mockingbirds Mimus saturninus
      are independent of clutch composition.
AB  - Obligate avian brood parasites lay their eggs in nests of other host species,
      which assume all the costs of parental care for the foreign eggs and chicks. The
      most common defensive response to parasitism is the rejection of foreign eggs by
      hosts. Different cognitive mechanisms and decision-making rules may guide both
      egg recognition and rejection behaviors. Classical optimization models generally
      assume that decisions are based on the absolute properties of the options (i.e.,
      absolute valuation). Increasing evidence shows instead that hosts' rejection
      decisions also depend on the context in which options are presented (i.e.,
      context-dependent valuation). Here we study whether the chalk-browed
      mockingbird's (Mimus saturninus) rejection of parasitic shiny cowbird (Molothrus
      bonariensis) eggs is a fixed behavior or varies with the context of the clutch.
      We tested three possible context-dependent mechanisms: (1) range effect, (2)
      habituation to variation, and (3) sensitization to variation. We found that
      mockingbird rejection of parasitic eggs does not change according to the
      characteristics of the other eggs in the nest. Thus, rejection decisions may
      exclusively depend on the objective characteristics of the eggs, meaning that the
      threshold of acceptance or rejection of a foreign egg is context-independent in
      this system.

PMID- 29372342
TI  - Determination of flutamide and two major metabolites using HPLC-DAD and HPTLC
      methods.
AB  - Flutamide is a potential antineoplastic drug classified as an anti-androgen. It
      is a therapy for men with advanced prostate cancer, administered orally after
      which it undergoes extensively first pass metabolism in the liver with the
      production of several metabolites. These metabolites are predominantly excreted
      in urine. One of the important metabolites in plasma is 4-nitro-3
      (trifluoromethyl)phenylamine (Flu-1), while the main metabolite in urine is 2
      amino-5-nitro-4-(trifluoromethyl)phenol (Flu-3). In this work the two
      metabolites, Flu-1 and Flu-3, have been synthesized, and then structural
      confirmation has been carried out by HNMR analysis. Efforts were exerted to
      develop chromatographic methods for resolving Flutamide and its metabolites with
      the use of acceptable solvents without affecting the efficiency of the methods.
      The drug along with its metabolites were quantitatively analyzed in pure form,
      human urine, and plasma samples using two chromatographic methods, HPTLC and HPLC
      DAD methods. FDA guidelines for bio-analytical method validation were followed
      and USP recommendations were used for analytical method validation. Interference
      from excipients has been tested by application of the methods to pharmaceutical
      tablets. No significant difference was found between the proposed methods and the
      official one when they were statistically compared at p value of 0.05%.

PMID- 29372343
TI  - Radio Frequency Ablation and Pulsed Radiofrequency for Treating Peripheral
      Neuralgias.
AB  - PURPOSE OF REVIEW: Peripheral nerve pain is common among patients with typical
      management including the use of pain medications, neuropathic agents, steroid
      injections, and nerve blocks. Additionally, the use of pulsed radiofrequency
      (PRF) and radiofrequency ablation (RFA) can be used in the management of chronic
      peripheral nerve pain. Previous studies investigating the effectiveness of RFA
      and PRF, typically case reports, have demonstrated that peripheral nerve RFA and
      PRF have the potential to provide relief of chronic pain for long duration. Our
      study aimed at testing efficacy of RFA/PRF for treating peripheral neuralgia.
      This was a retrospective review. We identified 16 patients who received 17
      RFAs/PRFs. Outcomes of interest collected included pain scores before and after
      procedures, percent improvement in pain after each procedure, and duration of
      improvement until the time of data collection. In addition, demographic data
      including age, sex, and nerves involved were collected. RECENT FINDINGS: Eleven
      patients (12 RFAs/PRFs) (80%) reported improvement after their procedure. Pain
      scores improved significantly from 6.3 +/- 2.3 before each procedure to 3.6 +/-
      2.7 after each procedure (p = 0.003). Eleven patients (12 RFAs/PRFs) reported an
      average improvement of 60.8% +/- 35% after their procedure with an average
      duration of improvement of 128.8 +/- 106.8 days. RFA and PRF can be used to treat
      chronic peripheral pain after conservative methods fail to do so. Large clinical
      trials are needed to confirm our finding.

PMID- 29372344
TI  - "We get them up, moving, and out the door. How do we get them to do what is
      recommended?" Using behaviour change theory to put exercise evidence into action
      for rehabilitation professionals.
AB  - : Recommendations suggest a multicomponent exercise for people with osteoporosis.
      We identified rehabilitation professionals' barriers and facilitators to
      implementing exercise recommendations with people with osteoporosis, and used
      those to make suggestions for targeted knowledge translation interventions.
      Future work will report on development and evaluation of the interventions
      informed by our study. PURPOSE: Rehabilitation professionals can help people with
      osteoporosis to engage in a multicomponent exercise program and perform
      activities of daily living safely. However, rehabilitation professional face
      barriers to implementing exercise evidence, especially for specific disease
      conditions like osteoporosis. We performed a behavioural analysis and identified
      rehabilitation professionals' barriers to and facilitators of implementing
      disease-specific physical activity and exercise recommendations (Too Fit to
      Fracture recommendations), and used the Behaviour Change Wheel to select
      interventions. METHODS: Semi-structured interviews and focus groups were
      conducted with rehabilitation professionals, including physical therapists,
      kinesiologists, and occupational therapists, and transcribed verbatim. Two
      researchers coded data and identified emerging themes. Using the Behaviour Change
      Wheel framework, themes were categorized into capability, opportunity, and
      motivation, and relevant interventions were identified. RESULTS: Ninety-four
      rehabilitation professionals (mean age 40.5 years, 88.3% female) participated.
      Identified barriers were as follows: capability-lack of training in behaviour
      change, how to modify recommendations for physical and cognitive impairments;
      opportunity-lack of resources, time, and team work; motivation-lack of trust
      between providers, fear in providing interventions that may cause harm.
      Interventions selected were as follows: education, training, enablement,
      modelling and persuasion. Policy categories are communication/marketing,
      guidelines, service provision and environmental/social planning. CONCLUSIONS: Key
      barriers to implementing the recommendations are rehabilitation professionals'
      ability to use behaviour change techniques, to modify the recommendations for
      physical and cognitive limitations and to feel comfortable with delivering
      challenging but safe interventions for people with osteoporosis, and lacking
      trust and team work across sectors. Future work will report on development and
      evaluation of knowledge translation interventions informed by our study.

PMID- 29372345
TI  - Correction to: Recurrence with pagetoid spread arising 17 years after surgery for
      intramucosal rectal cancer: a case report.
AB  - After publication of the original article [1] the authors noted that the
      following errors had occurred.

PMID- 29372346
TI  - Heavy Chain Disease of the Small Bowel.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss current knowledge and
      recent findings regarding pathogenesis, outcome, and treatment for heavy chain
      disease (HCD) involving the small bowel, focusing on alpha HCD or
      immunoproliferative small intestinal disease (IPSID), the HCD subtype typically
      affecting the small bowel. RECENT FINDINGS: A link between Campylobacter jejuni
      infection and IPSID has been established, but there is controversy as to the role
      played by this organism in disease pathogenesis. While cytogenetic abnormalities
      involving various immunoglobulin loci and PAX5 have been reported, these have
      been described in rare, single cases, limiting their ability to shed further
      light on disease pathogenesis. IPSID is typically regarded as a pre-lymphomatous
      condition with eventual progression to frank lymphoma; however, recent reports of
      longstanding non-progressive cases have expanded its clinical spectrum. IPSID is
      an uncommon disorder affecting the small intestine. This review focuses on
      current knowledge and novel insight regarding its pathogenesis, outcome, and
      treatment, with an emphasis on future directions.

PMID- 29372347
TI  - Thoracic wall muscle metastasis from pancreatic cancer.
AB  - Skeletal muscle metastasis from pancreatic cancer is rare. We present a 72-year
      old female patient with unresectable pancreatic tail cancer. Fifteen months after
      the introduction of the chemoradiotherapy, an 18-mm elastic hard tumor was found
      in her right chest wall and resected after confirmation of no other metastatic
      lesions. Postoperative pathological examination diagnosed it as a muscle
      metastasis from the pancreatic cancer, and the patient has since been continuing
      chemotherapy for 10 months. A review of the literature regarding skeletal muscle
      metastasis from pancreatic cancer is also presented.

PMID- 29372348
TI  - The Use of Autonomic Modulation Device to Control Training Performance after High
      Intensity Interval Training Program.
AB  - The aim of the present research was to analyze the autonomic response in a group
      of trained swimmers before and after conducting a 4-week period of high-intensity
      interval training (HIT). Heart rate variability was analyzed in 14 swimmers (16.2
      +/- 2.6 years, 169.1 +/- 10.2 cm and 61.3 +/- 9.9 kg) in basal condition and
      during a HIT session before and after completing a training period. The HIT
      session that was evaluated consisted of: 16 * 25 m maximum speed, resting 30 s
      between sets. Participants combined aerobic training with tethered swimming and
      HIT sessions three times per week in a period of 4 weeks. Results showed a
      significantly decrease (p < 0.05) of the standard deviation of the NN intervals
      (SDNN), the standard deviation of differences between adjacent NN intervals
      (SDSD), the number of successive difference of intervals which differ by more
      than 50 ms (NN50), after the training period. Results showed a higher
      parasympathetic activation besides improvements in autonomic adaptation after HIT
      training period.

PMID- 29372349
TI  - Cognitive impairment in rheumatoid arthritis: role of lymphocyte subsets,
      cytokines and neurotrophic factors.
AB  - To what extent the cognitive impairment of rheumatoid arthritis (RA) is modulated
      by autoimmune and/or inflammatory activity is largely unknown. The aim of this
      study was to investigate the role of peripheral inflammation on cognitive
      functions of patients with active (Ac-), controlled (Co-) RA and healthy
      controls. In a cross-sectional study, 102 RA patients and 30 matched healthy
      controls were recruited. B and T cell subsets were immunophenotyped by flow
      cytometry. Plasma cytokines and neurotrophins were measured by flow cytometry and
      ELISA, respectively. Cognitive performance, depression and stress were evaluated
      by structured clinical interviews. Generalized linear modeling (GzLM) was used to
      compare differences between groups and multiple linear regression models were
      used to explore the predictive value of immune variables on cognitive
      performance. RA patients had overall cognitive impairment. Of note, the Ac-RA had
      the poorest performance on digit span (DST) and N-back when compared to Co-RA and
      control group (DST 9.9 +/- 2.1, 12.9 +/- 4.2, 15.5 +/- 4.7, respectively; N-back
      49.2 +/- 8.3, 55.5 +/- 11.1, 60.8 +/- 9.1, respectively, all p < 0.0001). RA
      patients had expansions of immature B cells (Ac-RA 11.2 +/- 7.1, Co-RA: 9 +/-
      5.7, control 5.9 +/- 2.1) and plasma cells (Ac-RA 5.2 +/- 2.5, Co-RA 6.9 +/- 3.7,
      control 2.8 +/- 1.7) as compared to controls, all p < 0.05. RA patients
      (controlled and active disease) had higher plasma levels of TNF, IL-2, IL-4, IL-6
      and IL-10 than controls (all p < 0.002). RA patients had higher BDNF levels (Ac
      RA 17,354.4 +/- 5357.3, Co-RA 13,841.2 +/- 5953.7, control 11,543.3 +/- 3772),
      but lower GDNF levels [median (interquartile range) Ac-RA 0 pg/ml (0.0), Co-RA 0
      pg/ml (4.6) and control 4.7 pg/ml (18.1)] than controls (all p < 0.05). RA
      patients had global cognitive impairment, which was associated with disease
      activity and immune changes.

PMID- 29372350
TI  - Bilateral vision loss due to Leber's hereditary optic neuropathy after long-term
      alcohol, nicotine and drug abuse.
AB  - PURPOSE: Leber's hereditary optic neuropathy is relatively rare, and no clinical
      pathognomonic signs exist. We present a rare case of bilateral vision loss of a
      patient with multiple drug abuse in the history. OBSERVATION: A 31-year-old man
      presented with a history of progressive, decreased vision in both eyes for 6
      month. On examination, his visual acuity was hand motion in both eyes. Funduscopy
      demonstrated a temporal pallor of the optic disc. Goldmann visual field perimetry
      showed a crescent visual field in the right eye and a circular decrease to less
      than 50  degrees  in the left eye. Electroretinogram showed a scotopic b-wave
      amplitude reduction. Optical coherence tomographies, Heidelberg Retina
      tomography, visual evoked potentials, and magnetic resonance imaging with
      contrast as well as blood tests were normal. The patient reported to consume
      various kinds of drugs as well as recreational drug use and alcohol consumption
      since he was 16 years old. We started a hemodilution therapy, believing the
      patient suffered from a bilateral, toxic optic neuropathy due to his lifestyle.
      Laboratory results later on showed Leber's hereditary optic neuropathy.
      CONCLUSION AND IMPORTANCE: Leber's hereditary optic neuropathy is a rare disease
      without a typical, pathognomonic presentation. Even though the patient gave good
      reasons for a toxic optic neuropathy, one should never stop to test for other
      diseases.

PMID- 29372351
TI  - A Method for Guarding Animal Welfare and Public Health: Tracking the Rise of
      Backyard Poultry Ordinances.
AB  - In response to a growing number of permissive urban animal agriculture ordinances
      across the nation, this research reviews the spatial and temporal attributes of
      urban poultry ordinances across 100 municipalities in Colorado. More poultry
      ordinances have been passed or modified in Colorado in the last 5 years than in
      the previous hundred. Comparing regulations to commercial operations and animal
      shelter surrenders, we find that permissive ordinances cluster near major urban
      areas even where they are in close proximity to large commercial operations. Most
      ordinances inadequately address both human and animal health and welfare
      concerns. Provisions governing animal slaughter and routine veterinary care are
      rare, presenting a concern for monitoring and intervening in public health
      crises. In addition, shelters anticipate higher poultry intakes, particularly as
      unwanted birds are turned loose to become strays.

PMID- 29372352
TI  - Three dimensional models in uro-oncology: a future built with additive
      fabrication.
AB  - PURPOSE: Three-dimensional (3D) printing was invented in 1983 but has only just
      begun to influence medicine and surgery. Conversion of digital images into
      physical models demonstrates promise to revolutionize multiple domains of
      surgery. In the field of uro-oncology, researchers and clinicians have recognized
      the potential of this technology and are working towards making it an integral
      part of urological practice. We review current literature regarding 3D printing
      and other 3D technology in the field of urology. METHOD: A comprehensive
      assessment of contemporary literature was performed according to a modified
      PRISMA analysis for the purposes of this narrative review article. Medical
      databases that were searched included: Web of Science, EMBASE and Cochrane
      databases. Articles assessed were limited only to English-language peer-reviewed
      articles published between 1980 and 2017. The search terms used were "3D", "3
      dimensional", "printing", "printing technology", "urology", "surgery". Acceptable
      articles were reviewed and incorporated for their merit and relevance with
      preference given for articles with high impact, original research and recent
      advances. RESULTS: Thirty-five publications were included in final analysis and
      discussion. CONCLUSIONS: The area of 3D printing in Urology shows promising
      results, but further research is required and cost reduction must occur before
      clinicians fully embrace its use. As costs continue to decline and diversity of
      materials continues to expand, research and clinical utilization will increase.
      Recent advances have demonstrated the potential of this technology in the realms
      of education and surgical optimization. The generation of personalized organs
      using 3D printing scaffolding remains the 'holy grail' of this technology.

PMID- 29372353
TI  - Novel technology of molecular radio-guidance for lymph node dissection in
      recurrent prostate cancer by PSMA-ligands.
AB  - PURPOSE: Recently, prostate-specific membrane antigen-radioguided surgery (PSMA
      RGS) has been introduced as a promising new and individual treatment concept in
      patients with localised recurrent prostate cancer (PC). In the following, we want
      to review our experience with PSMA-RGS in patients with localised biochemical
      recurrent PC. METHODS: A non-systematic review of the literature was carried out
      with focus on technical and logistical aspects of PSMA-RGS. Furthermore,
      published data on intraoperative detection of metastatic lesions compared to
      preoperative PSMA-PET and postoperative histopathology, postoperative
      complications as well as oncological follow-up data are summarized. Finally,
      relevant aspects on prerequisites for PSMA-RGS, patient selection, and the
      potential benefit of additional salvage radiotherapy or potential future
      applications of robotic PSMA-RGS with drop-in gamma-probes are discussed.
      RESULTS: First results show that PSMA-RGS is very sensitive and specific in
      tracking suspicious lesions intraoperatively. Prerequisite for patient selection
      and localisation of tumour recurrence is a positive Ga-HBED-CC PSMA positron
      emission tomography (PET) scan with preferably only singular soft tissue or lymph
      node recurrence after primary treatment. Furthermore, PSMA-RGS has the potential
      to positively influence oncological outcome. CONCLUSIONS: PSMA-RGS seems to be of
      high value in patients with localised PC recurrence for exact localisation and
      resection of oftentimes small metastatic lesions using intraoperative and ex vivo
      gamma-probe measurements. However, patient identification on the basis of Ga-HBED
      CC-PSMA PET imaging as well as clinical parameters is crucial to obtain
      satisfactory results.

PMID- 29372354
TI  - Urinary tract infections following radical cystectomy and urinary diversion: a
      review of 1133 patients.
AB  - OBJECTIVE: To investigate the incidence and microbiology of urinary tract
      infection (UTI) within 90 days following radical cystectomy (RC) and urinary
      diversion. METHODS: We reviewed 1133 patients who underwent RC for bladder cancer
      at our institution between 2003 and 2013; 815 patients (72%) underwent orthotopic
      diversion, 274 (24%) ileal conduit, and 44 (4%) continent cutaneous diversion. 90
      day postoperative UTI incidence, culture results, antibiotic
      sensitivity/resistance and treatment were recorded through retrospective review.
      Fisher's exact test, Kruskal-Wallis test, and multivariable analysis were
      performed. RESULTS: A total of 151 urinary tract infections were recorded in 123
      patients (11%) during the first 90 days postoperatively. 21/123 (17%) had
      multiple infections and 25 (20%) had urosepsis in this time span. Gram-negative
      rods were the most common etiology (54% of positive cultures). 52% of UTI
      episodes led to readmission. There was no significant difference in UTI rate,
      etiologic microbiology (Gram-negative rods, Gram-positive cocci, fungi), or
      antibiotic sensitivity and resistance patterns between diversion groups.
      Resistance to quinolones was evident in 87.5% of Gram-positive and 35% of Gram
      negative bacteria. In multivariable analysis, Charlson Comorbidity Index > 2 was
      associated with higher 90-day UTI rate (OR = 1.8, 95% CI 1.1-2.9, p = 0.05) and
      Candida UTI (OR 5.6, 95% CI 1.6-26.5, p = 0.04). CONCLUSIONS: UTI is a common
      complication and cause of readmission following radical cystectomy and urinary
      diversion. These infections are commonly caused by Gram-negative rods. High
      comorbidity index is an independent risk factor for postoperative UTI, but
      diversion type is not.

PMID- 29372355
TI  - Worth a second look: outcomes of patients with initial finding of regular renal
      tissue in CT-guided renal tumor biopsies.
AB  - INTRODUCTION AND OBJECTIVE: Renal tumor biopsy is recommended for histological
      diagnosis of radiologically indeterminate renal masses, to select patients with
      small-renal masses for surveillance approaches, before ablative treatments and to
      confirm metastatic spread of renal cell cancer (RCC), according to the EAU
      guidelines. We aimed to determine outcomes of patients with suspicious renal
      masses with initial finding of regular renal tissue in renal tumor biopsies.
      METHODS: Retrospective database analysis of 101 patients undergoing CT-guided-,
      percutaneous renal tumor biopsies in local anesthesia. RESULTS: In 23/101
      patients, histopathologic evaluation of the biopsies showed regular renal tissue.
      Of these, two patients underwent simultaneous radiofrequency ablation (RFA), 2/23
      underwent radical nephrectomy, despite negative biopsy because of radiological
      suspicious aspect. Overall, 12 patients underwent a second set of biopsies due to
      persistent clinical suspicion. Of these, five were diagnosed with RCC: three
      clear cell renal cell carcinoma (ccRCC) and two papillary renal cell carcinoma
      (pRCC). Benign tumours were found in two patients. A lymphoma was found in two
      patients. In 3/12 patients, also the second set of biopsies showed regular renal
      tissue. CONCLUSION: An unsuspicious histology in CT-guided renal tumor biopsy
      does not preclude patients with suspicious renal masses from being diagnosed with
      malignancies.

PMID- 29372356
TI  - Evaluation of clinical staging of the American Joint Committee on Cancer (eighth
      edition) for prostate cancer.
AB  - OBJECTIVES: This study aimed to evaluate the eighth edition of the American Joint
      Committee on Cancer (AJCC) for clinical staging of prostate cancer based upon
      Surveillance, Epidemiology and, End Results (SEER) database. MATERIALS AND
      METHODS: Patients diagnosed as prostate adenocarcinoma during 2004-2009 without
      any surgical treatment to the primary site were selected from the SEER registry.
      Excluded were cases with incomplete or unavailable staging, PSA and Gleason score
      information. RESULTS: A total of 144,443 cases were identified. The median follow
      up time was 84 months. The median age at diagnosis was 69 years, and median PSA
      was 7 ng/ml. CSS at 10th years was 96.2% for cT2a and 86.2% for cT2b/2c,
      respectively. The survival differences between clinical stage cT2a and cT2b/2c
      still had statistical significance (P < 0.001). For patients with grade group 1,
      there was no statistically significant difference for CCS between the cT2a and
      cT1 (P = 0.310), and between the subgroup of cT1/cT2a with 10 ng/ml <= PSA < 20
      ng/ml and the subgroup of cT2b/2c with PSA < 20 ng/ml (P = 0.126), respectively.
      The CSS of IIIA (T1/2 with PSA >= 20 ng/ml) was less than IIC (P < 0.001), which
      has worst prognosis within stage I/II. The prognosis of T1/2 stage with Gleason
      score grade group 5 and PSA < 20 ng/ml was not only worse than AJCC IIC (P <
      0.001) but also worse than AJCC IIIB (P < 0.001). CONCLUSION: It is necessary to
      maintain a three-tier system to subdivide T2 disease clinically. For patients
      with grade group 1, cT2a and cT1 could merge into one group. Organ-confined
      disease with PSA >= 20 ng/ml or grade group 5 should be separated from stage II.

PMID- 29372357
TI  - Micro-ureteroscopy vs. ureteroscopy: effects of miniaturization on renal
      vascularization and intrapelvic pressure.
AB  - PURPOSE: Ureteroscopy (URS) is related to complications, as fever or
      postoperative urinary sepsis, due to high intrapelvic pressure (IPP) during the
      procedure. Micro-ureteroscopy (m-URS) aims to reduce morbidity by miniaturizing
      the instrument. The objective of this study is to compare IPP and changes in
      renal haemodynamics, while performing m-URS vs. conventional URS. METHODS: A
      porcine model involving 14 female pigs was used in this experimental study. Two
      surgeons performed 7 URS (8/9.8 Fr), for 45 min, and 7 m-URS (4.85 Fr), for 60
      min, representing a total of 28 procedures in 14 animals. A catheter pressure
      transducer measured IPP every 5 min. Haemodynamic parameters were evaluated by
      Doppler ultrasound. The volume of irrigation fluid employed in each procedure was
      also measured. RESULTS: The range of average pressures was 5.08-14.1 mmHg in the
      m-URS group and 6.08-20.64 mmHg in the URS (NS). 30 mmHg of IPP were not reached
      in 90% of renal units examined with m-URS, as compared to 65% of renal units in
      the URS group. Mean peak diastolic velocity decreased from 15.93 to 15.22 cm/s
      (NS) in the URS group and from 19.26 to 12.87 cm/s in the m-URS group (p < 0.01).
      Mean resistive index increased in both groups (p < 0.01). Irrigation fluid volume
      used was 485 mL in the m-URS group and 1475 mL in the URS group (p < 0.001).
      CONCLUSIONS: m-URS requires less saline irrigation volumes than the conventional
      ureteroscopy and increases renal IPP to a lesser extent.

PMID- 29372358
TI  - Laryngeal Manipulation for Dysphagia with Muscle Tension Dysphonia.
AB  - The purpose of the article is to describe the use of laryngeal manipulation as a
      treatment for dysphagia resulting from excessive paralaryngeal muscle tension and
      to identify the patients likely to have symptomatic improvement. This is a
      retrospective single-center case series. A retrospective review identified
      patients from 2007 to 2013 with laryngeal manipulation for muscle tension
      dysphagia in an academic Otolaryngology practice. Subjects with dysphagia not
      attributable to an anatomic cause who attended therapy at least one time were
      included in the study. The primary outcome of the study was subjective
      improvement in dysphagia symptoms (yes/no) during follow-up. Symptoms,
      demographic information, treatment, and response to therapy were recorded. The
      Kruskal-Wallis test was used for analysis of continuous variables, while a Chi
      squared test or fisher's exact test was used for analysis of all categorical
      variables. Forty-four subjects were included, consisting of 37 women and 7 men.
      Subjective improvement in dysphagia was seen in 34 subjects (77.3%). No
      significant differences were seen in improvement based on gender (p = 0.3223),
      race (p = 0.4317), number of sessions with a speech pathologist (p = 0.3198), or
      presenting symptoms including hoarseness (p = 0.0853), pain (p = 1.000), globus
      (p = 0.2834), and cough (p = 1.000). We found subjective improvement with
      laryngeal manipulation as reported during follow-up visits to clinic among
      individuals with muscle tension dysphagia. Patient age, presenting symptoms, and
      number of therapy sessions were not found to be significantly associated with
      resolution of symptoms.

PMID- 29372359
TI  - Anti-inflammatory and antinociceptive properties of the hydroalcoholic fractions
      from the leaves of Annona crassiflora Mart. in mice.
AB  - BACKGROUND: Annona crassiflora Mart., popularly known as "Araticum", is a native
      tree of the Brazilian Cerrado used in folk medicine for treatment of pain and
      inflammatory diseases. We proposed to analyze analgesic and anti-inflammatory
      properties of the filtrate (F1) and the precipitate (F2) of the hydroalcoholic
      fraction from the leaves of Annona crassiflora Mart. in mice. MATERIALS AND
      METHODS: Swiss mice were submitted to formalin-induced nociception test and tail
      flick reflex test, to assess antinociceptive properties, and to the rota-rod
      test, for motor performance analyses. To evaluate anti-inflammatory properties,
      F1 and F2 were orally administered 1 h prior to the intrathoracic injection of
      carrageenan, zymosan, LPS, CXCL8, or vehicle in Balb/c mice and neutrophil
      infiltration was evaluated 4 h after injection. RESULTS: F1 and F2 reduced the
      licking time in the second phase of formalin-induced nociception test, but only
      F2 showed a dose-dependent response. Neither F1 nor F2 reduced the latency time
      in the tail-flick reflex test. In addition, motor performance alteration was not
      observed in F1- or F2-treated mice. F2 treatment significantly inhibited the
      neutrophilia induced by carrageenan, LPS, or CXCL8, but not zymosan. CONCLUSIONS:
      The experimental data demonstrated that hydroalcoholic fractions of Annona
      crassiflora Mart. leaves have remarkable anti-inflammatory and antinociceptive
      activities.

PMID- 29372360
TI  - Ranking composite Cancer Burden Indices for geographic regions: point and
      interval estimates.
AB  - PURPOSE: To develop a composite Cancer Burden Index and produce 95% confidence
      intervals (CIs) as measures of uncertainties for the index. METHODS: The Kentucky
      Cancer Registry has developed a cancer burden Rank Sum Index (RSI) to guide
      statewide comprehensive cancer control activities. However, lack of interval
      estimates for RSI limits its applications. RSI also weights individual measures
      with little inherent variability equally as ones with large variability. To
      address these issues, a Modified Sum Index (MSI) was developed to take into
      account of magnitudes of observed values. A simulation approach was used to
      generate individual and simultaneous 95% CIs for the rank MSI. An uncertainty
      measure was also calculated. RESULTS: At the Area Development Districts (ADDs)
      level, the ranks of the RSI and the MSI were almost identical, while larger
      variation was found at the county level. The widths of the CIs at the ADD level
      were considerably shorter than those at the county level. CONCLUSION: The
      measures developed for estimating composite cancer burden indices and the
      simulated CIs provide valuable information to guide cancer prevention and control
      effort. Caution should be taken when interpreting ranks from small population
      geographic units where the CIs for the ranks overlap considerably.

PMID- 29372361
TI  - Lp (p <= 1) Norm Partial Directed Coherence for Directed Network Analysis of
      Scalp EEGs.
AB  - Partial directed coherence (PDC), which is capable of estimating directed brain
      networks in the frequency domain, has been widely used in various physiological
      recordings such as electroencephalograms (EEGs) and functional magnetic resonance
      imaging. However, clinical data from EEGs are inevitably contaminated with
      unexpected outlier artifacts. This will result in biased networks, which are
      different from the original physiological mechanism because of the L2 norm
      structure utilized in PDC to estimate the directed links. In this work, we define
      a new PDC model in the Lp norm (p <= 1) space to restrict outlier influence and
      use a feasible iteration procedure to solve this model for directed network
      construction. The quantitative evaluation using a predefined simulation network
      demonstrates that Lp-PDC is more consistent with the predefined networks than LS
      PDC and Lasso-PDC under various simulated outlier conditions. Applying the Lp-PDC
      model to resting-state EEGs with ocular artifacts also show that the proposed PDC
      can effectively restrict the ocular artifacts to recover the networks, which is
      also more consistent with the physiological basis. Both simulation and real-life
      EEG applications demonstrate the efficiency of the proposed PDC in suppressing
      the influence of outliers in EEG signals, and the proposed Lp-PDC may be helpful
      to capture reliable causal relationships for related studies contaminated with
      outlier artifacts.

PMID- 29372362
TI  - Large-Scale Traveling Waves in EEG Activity Following Eye Movement.
AB  - In spontaneous, stimulus-evoked, and eye-movement evoked EEG, the oscillatory
      signal shows large scale, dynamically organized patterns of phase. We
      investigated eye-movement evoked patterns in free-viewing conditions.
      Participants viewed photographs of natural scenes in anticipation of a memory
      test. From 200 ms intervals following saccades, we estimated the EEG phase
      gradient over the entire scalp, and the wave activity, i.e. the goodness of fit
      of a wave model involving a phase gradient assumed to be smooth over the scalp.
      In frequencies centered at 6.5 Hz, large-scale phase organization occurred,
      peaking around 70 ms after fixation onset and taking the form of a traveling
      wave. According to the wave gradient, most of the times the wave spreads from the
      posterior-inferior to anterior-superior direction. In these directions, the
      gradients depended on the size and direction of the saccade. Wave propagation
      velocity decreased in the course of the fixation, particularly in the interval
      from 50 to 150 ms after fixation onset. This interval corresponds to the fixation
      related lambda activity, which reflects early perceptual processes following
      fixation onset. We conclude that lambda activity has a prominent traveling wave
      component. This component consists of a short-term whole-head phase pattern of
      specific direction and velocity, which may reflect feedforward propagation of
      visual information at fixation.

PMID- 29372363
TI  - Tumor-Specific Labeling of Pancreatic Cancer Using a Humanized Anti-CEA Antibody
      Conjugated to a Near-Infrared Fluorophore.
AB  - BACKGROUND/PURPOSE: Development of a humanized fluorophore-conjugated antibody
      that can improve contrast for fluorescence-guided oncologic surgeries. METHODS:
      BxPC-3-GFP pancreatic cancer cells were injected into flanks of nude mice.
      Fragments of subcutaneous tumors were grafted onto the pancreatic tail of
      recipient mice to create orthotopic xenograft models of pancreatic cancer. After
      tumors developed for 4 weeks, a humanized anti-carcinoembryonic antigen antibody
      conjugated to an 800 nm near-infrared fluorescent dye (hM5A-IR800) was injected
      intravenously. Mice were imaged at 6, 12, 24, 48, and 72 h after injection.
      RESULTS: Fluorescence imaging showed that hM5A-IR800 specifically localized to
      BxPC-3 human pancreatic cancer cells. The fluorescent probe localized to cell
      surfaces in vitro and specifically co-localized with green fluorescent protein
      labeled tumors in an orthotopic pancreatic xenograft model in vivo. Serial
      imaging at specific time points showed peak signal intensity of the orthotopic
      pancreatic tumor at 48 h; this time point corresponded with a maximal tumor-to
      background ratio (TBR) of 16.6 at 48 h. DISCUSSION: hM5A-IR800 was successfully
      able to specifically label orthotopic pancreatic tumors in situ. The longer
      wavelength allowed deeper tissue penetration, particularly in tumor areas covered
      by normal pancreatic parenchyma. The probe had expected kinetics for an antibody
      fluorophore conjugate, with the peak signal intensity reached at 48 h. A clear
      tumor signal was observed with a TBR > 5 at all time points, with high contrast
      (TBR of 16.6) at 48 h. CONCLUSION: hM5A-IR800 demonstrated excellent tumor
      localization and a very bright signal. It is a promising agent for future
      clinical fluorescence-guided surgery applications.

PMID- 29372364
TI  - Reproductive Decision Support: Preferences and Needs of Couples at Risk for
      Hereditary Cancer and Clinical Geneticists.
AB  - : For couples at high risk of transmitting a cancer predisposition to offspring,
      reproductive decision-making can be challenging. As the choice between available
      reproductive options is preference-sensitive, the use of a decision aid can
      support these couples in their decisional process. The present study aims to
      investigate preferences and needs of involved stakeholders regarding the
      development and implementation of a patient decision aid. Semi-structured
      interviews assessing the needs and preferences regarding the content and
      functionalities of a decision support program were conducted among seven couples
      at risk for hereditary cancer and among eight clinical geneticists involved in
      oncogenetic counseling. Many similarities were found between the expressed
      preferences and needs of both stakeholder groups concerning the content, barriers
      and facilitating factors regarding the use of the decision aid, and its
      implementation. Emphasis was placed on the use of simple non-medical language, an
      extensive explanation of the procedures and techniques used in prenatal diagnosis
      (PND) and preimplantation genetic diagnosis (PGD), and the role of health care
      providers to refer couples to the decision aid. Both stakeholder groups were in
      favor of incorporating narrative stories in the decision aid. Integrating the
      present findings with knowledge on reproductive decisional motives and
      considerations is essential in guiding the development of a decision aid that
      corresponds to the preferences and needs of end-users. TRIAL REGISTRATION:
      NTR5467.

PMID- 29372365
TI  - How Might the Genetics Profession Better Utilize Social Media.
AB  - Social media is a common method of communication in people's personal lives and
      professional settings. Gallagher et al. (2016) recommended, "it is time for
      genetic counselors to embrace social media as a means of communicating with
      patients or other healthcare professionals." Full members of the National Society
      of Genetic Counselors (NSGC) in the USA and Canada and genetics patients in
      Cleveland, OH, were surveyed to determine interest in using social media for
      patient-provider interactions. Both cohorts indicated that patient privacy and
      confidentiality would be a concern; however, survey results indicated patients
      would be interested in using social media to receive general information about
      genetic counseling and to learn about genetics services. Genetic counselors
      indicated privacy issues were not concerning if social media were to be used in
      this capacity. The majority of genetic counselor participants (88.7%) indicated
      they would welcome national guidelines for patient-provider social media use.
      Data from this study demonstrated that sharing what to expect at a genetic
      counseling appointment, defining genetic counseling, and announcing community
      outreach events are possible ways genetic counselors could utilize social media
      to communicate with and educate patients.

PMID- 29372366
TI  - Lethal and sublethal effects of metal-polluted sediments on Chironomus
      sancticaroli Strixino and Strixino, 1981.
AB  - The Cantareira Complex is one of the most important water supplies of the
      metropolitan region of Sao Paulo, Brazil. Previously, it was demonstrated that
      the sediments in this complex were polluted with metals and that Paiva Castro
      Reservoir-the last reservoir in the sequence, which receives water from the five
      previous reservoirs-was the reservoir with the greatest concentration of
      pollutants. Based on field data, it was noticed that copper concentrations in
      sediments were related to morphological alterations in chironomids. The present
      study provides novel monitoring methods and results for the complex by isolating
      the environmental and biological sources of variation. An adaptation of the in
      situ assay proposed by Soares et al. (Arch Environ Contam Toxicol 49:163-172,
      2005), which uses a native tropical Chironomus species and low-cost materials, is
      also provided. The aim of this study was to isolate the effects of sediments from
      Paiva Castro on controlled populations of C. sancticaroli larvae using an in situ
      assay. A seven-day experiment was performed in triplicate. Third instar larvae
      were inoculated in chambers containing sediments from two distinct regions of
      Paiva Castro reservoir and a control site with sand. Five biological responses
      were considered: mouthpart alterations, larval length, width of cephalic capsule,
      mortality and total damage. The results suggest the effects of sediment toxicity
      on larvae include a reduction in length and a higher occurrence of total damage.

PMID- 29372368
TI  - Correction to: Emotion Regulation via the Autonomic Nervous System in Children
      with Attention-Deficit/Hyperactivity Disorder (ADHD).
AB  - This erratum reports an error in Musser, E. D., Backs, R. W., Schmitt, C. F.,
      Ablow, J. C., Measelle, J. R., & Nigg, J. T. (2011). Emotion regulation via the
      autonomic nervous system in children with attention-deficit/hyperactivity
      disorder (ADHD).

PMID- 29372367
TI  - An Imbalance of Approach and Effortful Control Predicts Externalizing Problems:
      Support for Extending the Dual-Systems Model into Early Childhood.
AB  - Although the association between deficits in effortful control and later
      externalizing behavior is well established, many researchers (Nigg Journal of
      Child Psychology and Psychiatry, 47(3-4), 395-422, 2006; Steinberg Developmental
      Review, 28(1), 78-106, 2008) have hypothesized this association is actually the
      product of the imbalance of dual systems, or two underlying traits: approach and
      self-regulation. Very little research, however, has deployed a statistically
      robust strategy to examine that compelling model; further, no research has done
      so using behavioral measures, particularly in longitudinal studies. We examined
      the imbalance of approach and self-regulation (effortful control, EC) as
      predicting externalizing problems. Latent trait models of approach and EC were
      derived from behavioral measures collected from 102 children in a community
      sample at 25, 38, 52, and 67 months (2 to 5 1/2 years), and used to predict
      externalizing behaviors, modeled as a latent trait derived from parent-reported
      measures at 80, 100, 123, and 147 months (6 1/2 to 12 years). The imbalance
      hypothesis was supported: Children with an imbalance of approach and EC had more
      externalizing behavior problems in middle childhood and early preadolescence,
      relative to children with equal levels of the two traits.

PMID- 29372369
TI  - "Transcriptomics": molecular diagnosis of inborn errors of metabolism via RNA
      sequencing.
AB  - Exome wide sequencing techniques have revolutionized molecular diagnostics in
      patients with suspected inborn errors of metabolism or neuromuscular disorders.
      However, the diagnostic yield of 25-60% still leaves a large fraction of
      individuals without a diagnosis. This indicates a causative role for non-exonic
      regulatory variants not covered by whole exome sequencing. Here we review how
      systematic RNA-sequencing analysis (RNA-seq, "transcriptomics") lead to a
      molecular diagnosis in 10-35% of patients in whom whole exome sequencing failed
      to do so. Importantly, RNA-sequencing based discoveries cannot only guide
      molecular diagnosis but might also unravel therapeutic intervention points such
      as antisense oligonucleotide treatment for splicing defects as recently reported
      for spinal muscular atrophy.

PMID- 29372370
TI  - SLC30A family expression in the pancreatic islets of humans and mice: cellular
      localization in the beta-cells.
AB  - Zinc is a vital co-factor for insulin metabolism in the pancreatic beta-cell,
      involved in synthesis, maturation, and crystallization. Two families of zinc
      transporters, namely SLC30A (ZNT) and SLC39A (ZIP) are involved in maintaining
      cellular zinc homeostasis in mammalian cells. Single nuclear polymorphisms or
      mutations in zinc transporters have been associated with insulin resistance and
      risk of type 2 diabetes (T2D) in both humans and mice. Thus, mice can be useful
      for studying the underlying mechanisms of zinc-associated risk of T2D
      development. To determine potential differences in zinc transporter expression
      and cellular localization in the pancreatic beta-cells between humans and mice,
      we examined all members (ZNT1-10) of the ZNT family in pancreatic islets and in
      beta-cell lines derived from both species using immunohistochemistry and
      immunofluorescence microscopic analysis. We found that there were no substantial
      differences in the expression of nine ZNT proteins in the human and mouse islets
      and beta-cells with exception of ZNT3, which was only detected in human beta
      cells, but not in mouse beta-cells. Moreover, we found that ZNT2 was localized on
      the cell surface of both human and mouse beta-cells, suggesting a role of ZNT2 in
      direct export of zinc out of the beta-cell. Together, our study suggests
      functional conservations of the ZNT proteins between humans and mice. We believe
      that our results are of interest for future studies in the association of zinc
      metabolism with risk of T2D in humans using mouse models.

PMID- 29372371
TI  - Surgical treatment of patients with myelomeningocele-related spine deformities:
      study of 26 cases.
AB  - INTRODUCTION: Scoliosis, kyphosis, and sacral agenesis (SA) are common spine
      deformities in myelomeningocele (MMC) patients. Surgery of spine deformities in
      MMC patients is associated with various difficulties as infection, pathological
      skin breakage, instrumentation failure, and neurological deterioration. The
      purposes of this study are to share our clinical experience and discuss different
      surgical techniques which are defined in the literature. PATIENTS AND METHOD: We
      retrospectively evaluated our database of patients with MMC who underwent
      surgical procedures for spine deformities from 2014 to 2016. Demographic and
      clinical data, surgical parameters, surgical techniques and levels, pre- and
      postoperative deformity angles, level of posterior fusion defect, spinal
      malformations, neurological evaluation of lower extremities and complications
      were collated. We divided the cases into three groups according to the type of
      deformities. The groups were lumbar kyphosis (Group 1), congenital scoliosis
      (Group 2), and paralytic scoliosis (Group 3). RESULTS: There were 26 patients in
      the study. Fifteen patients were male and 11 patients were female. The median age
      of the patients was 8.03 (range = 3-17 years) at the time of operation. There
      were 10 patients in Group 1, 7 patients in Group 2, and 9 patients in Group 3. In
      Group 1, preoperative kyphosis angle varied between 51 degrees  and 160 degrees ,
      with an average of 95.7 degrees . In Group 2, preoperative Cobb angle varied
      between 57 degrees  and 150 degrees , with an average of 106.6 degrees . Kyphosis
      was present in 4 patients. Preoperative kyphosis angle varied between 74 degrees 
      and 140 degrees , with an average of 93 degrees . In Group 3, preoperative Cobb
      angle varied between 45 degrees  and 145 degrees , with an average of 72.5
      degrees . CONCLUSION: Spinal deformity in children with MMC has been considered
      to cause severe disability. Surgical treatment is a challenging procedure with a
      wide spectrum of complications, but can provide good correction of spinal
      deformity and pelvic obliquity, and improve the quality of life. Self-growing
      systems which are a new alternative to traditional growing rod systems, must be
      considered to preserve growing potential of spine.

PMID- 29372372
TI  - Surgery for Hepatocellular Carcinoma in Patients with Child-Pugh B Cirrhosis:
      Hepatic Resection Versus Living Donor Liver Transplantation.
AB  - BACKGROUND: Liver transplantation has been established as the optimal treatment
      for hepatocellular carcinoma in cirrhotic patients, but hepatic resection is also
      effective in patients with well-preserved liver function. Determining the
      suitable surgical treatment for patients with Child-Pugh class B cirrhosis is a
      more difficult challenge. METHODS: We retrospectively compared the results of
      hepatic resection and living donor liver transplantation for hepatocellular
      carcinoma in 137 patients with Child-Pugh class B cirrhosis. The procedures were
      performed at Kyushu University Hospital from April 2014 through October 2016.
      RESULTS: Patients who underwent hepatic resection were significantly older and
      had better liver function, larger tumor size, smaller number of tumors, and less
      surgical stress compared with patients who underwent living donor liver
      transplantation. The overall survival rate and the recurrence-free survival rate
      in patients with transplantation were significantly better than that in patients
      with resection. The multivariate analysis showed that recurrent hepatocellular
      carcinoma and microvascular invasion were significant prognostic factors for both
      overall and recurrence-free survival in the hepatic resection group. In the group
      with protein induced by vitamin K absence or antagonist-II >=300 mAU/mL, both the
      overall survival curve and the recurrence-free survival curve in patients with
      living donor liver transplantation were not significantly different from those in
      patients with hepatic resection. CONCLUSIONS: Living donor liver transplantation
      for hepatocellular carcinoma in patients with Child-Pugh class B cirrhosis was
      favorable under the condition of protein induced by vitamin K absence or
      antagonist-II <300 mAU/mL in selected recipients and donors. Hepatic resection
      for recurrent hepatocellular carcinoma and excessive blood loss should be avoided
      in patients with Child-Pugh class B cirrhosis.

PMID- 29372373
TI  - Excellent Prognosis of Central Lymph Node Recurrence-Free Survival for cN0M0
      Papillary Thyroid Carcinoma Patients Who Underwent Routine Prophylactic Central
      Node Dissection.
AB  - INTRODUCTION: In Japan, prophylactic central node dissection (p-CND) for
      papillary thyroid carcinoma (PTC) has been routinely performed in many
      institutions, including ours (Kuma Hospital, Japan). We evaluated the recurrence
      to a central lymph node in patients with cN0M0 PTC who underwent routine p-CND.
      MATERIALS AND METHODS: We enrolled 4301 patients with cN0M0 PTC who underwent an
      initial surgery between 1987 and 2005 (median age 51 years). The postoperative
      follow-up periods ranged from 4 to 362 months (median 164 months). Only 15
      patients underwent radioactive iodine (RAI) ablation (>=30 mCi) after total or
      near total thyroidectomy. RESULTS: Of the 4301 patients with N0M0 PTC who
      underwent p-CND, 2548 (59%) were diagnosed as pN1a on postoperative pathological
      examination. To date, only 52 cases (1.2%) showed recurrence to a central lymph
      node. The 10-year and 20-year central node recurrence-free survival rates were
      excellent at 99.1 and 98.2%, respectively. On multivariate analysis, age >=55
      years, significant extrathyroid extension, tumor size >2 cm, and >=5
      pathologically confirmed central node metastases (but not the presence of central
      node metastasis) independently affected central node recurrence. CONCLUSIONS:
      Under the situation of routine p-CND, the central node recurrence-free survival
      of cN0M0 PTC is excellent. However, future studies, including double-arm studies
      from Japan, should examine whether the omission of p-CND cN0M0 PTC is appropriate
      without RAI ablation in consideration of various factors, including the pros and
      cons of p-CND.

PMID- 29372374
TI  - Cysto-cholecystostomy: A More Physiological Procedure for Hepatic Cysts with
      Biliary Communications and Cystic Dilatations of Main Intrahepatic Ducts.
AB  - OBJECTIVE: Hepatic cysts with biliary communications (HC) and cystic dilatations
      of main intrahepatic ducts (CIHD) can cause biliary obstruction, cholestasis,
      stone formation, cholangitis, liver damage and carcinoma. Conventionally, Roux-Y
      cysto-jejunostomy is employed to manage these conditions. However, it is
      technically demanding and may be complicated with major biliary disruption and
      bacteria migration from intestine to intrahepatic duct. We have carried out
      laparoscopic cysto-cholecystostomies for HC with biliary communication and CIHD
      and evaluated outcomes. METHODS: Twenty patients with HC (n = 10) or CIHD (n =
      10) who successfully underwent laparoscopic cysto-cholecystostomies in our
      center, between September 2010 and March 2017, were reviewed. RESULTS: The mean
      age of the patients at surgery was 2.06 and 2.23 years for HC and CIHD groups,
      respectively. Eighteen patients were symptomatic, with abdominal pain, fever,
      vomiting and jaundice. Laboratory results showed abnormal liver functions in 8
      patients. Pathological results verified hepatic cellular damages in 8 patients.
      The mean operative time was 0.97 and 0.92 h for HC and CIHD patients,
      respectively. The median follow-up duration was 27 months (1-54 months) and 35
      months (1-79 months) for HC and CIHD groups, respectively. No patient developed
      bile leak, anastomotic stenosis, stone formation or cholangitis. Liver function
      normalized postoperatively. CONCLUSIONS: Laparoscopic cysto-cholecystostomy is a
      simpler and more physiological surgical alternative for managing HC with biliary
      communication and CIHD.

PMID- 29372375
TI  - Endoluminal Vacuum Therapy (E-Vac): A Treatment Option in Oesophagogastric
      Surgery.
AB  - BACKGROUND: Leaks from the upper gastrointestinal tract often pose a management
      challenge, particularly when surgical treatment has failed or is impossible.
      Vacuum therapy has revolutionised the treatment of wounds, and its role in
      enabling and accelerating healing is now explored in oesophagogastric surgery.
      METHODS: A piece of open cell foam is sutured around the distal end of a
      nasogastric tube using a silk suture. Under general anaesthetic, the foam covered
      tip is placed endoscopically through the perforation and into any extra-luminal
      cavity. Continuous negative pressure (125 mmHg) is then applied. Re-evaluation
      with change of the negative pressure system is performed every 48-72 h depending
      on the clinical condition. Patients are fed enterally and treated with broad
      spectrum antibiotics and anti-fungal medication until healing, assessed
      endoscopically and/or radiologically, is complete. RESULTS: Since April 2011,
      twenty one patients have been treated. The cause of the leak was
      postoperative/iatrogenic complications (14 patients) and ischaemic/spontaneous
      perforation (seven patients). Twenty patients (95%) completed treatment
      successfully with healing of the defect and/or resolution of the cavity and were
      subsequently discharged from our care. One patient died from sepsis related to an
      oesophageal leak after withdrawing consent for further intervention following a
      single endoluminal vacuum (E-Vac) treatment. In addition, two patients who were
      successfully treated with E-Vac for their leak subsequently died within 90 days
      of E-Vac treatment from complications that were not associated with the E-Vac
      procedure. In two patients, E-Vac treatment was complicated by bleeding. The
      median number of E-Vac changes was 7 (range 3-12), and the median length of
      hospital stay was 35 days (range 23-152). CONCLUSIONS: E-Vac therapy is a safe
      and effective treatment for upper gastrointestinal leaks and should be considered
      alongside more established therapies. Further research is now needed to
      understand the mechanism of action and to improve the ease with which E-Vac
      therapy can be delivered.

PMID- 29372376
TI  - Remote effects in the ipsilateral thalamus and/or contralateral cerebellar
      hemisphere using FDG PET in patients with brain tumors.
AB  - PURPOSE: To evaluate reduced metabolism in the ipsilateral thalamus (TH) and/or
      contralateral cerebellum (CE) according to tumor localization and cortical
      metabolism around the tumor in patients with brain tumors based on FDG uptake.
      METHODS: This study investigated 48 consecutive patients with solitary cerebral
      hemisphere parenchymal brain tumors who underwent PET/CT and MRI. Patients were
      divided into 4 groups (A: reduced uptake in ipsilateral TH and contralateral CE,
      B: reduced uptake in ipsilateral TH only, C: reduced uptake in contralateral CE
      only, and D: no reduced uptake in ipsilateral TH or contralateral CE). FDG uptake
      and MRI findings were compared among these groups. RESULTS: Of 48 patients, group
      A included 24 (50%), group B included 10 (21%), group C included 0, and group D
      included 14 (29%). No significant tendencies were observed between the groups
      regarding tumor localization. However, reduced cortical metabolism around the
      tumor was observed in 22 patients in group A, 7 patients in group B, and 1
      patient in group D. All patients in group B showed reduced metabolism from around
      the tumor up to the ipsilateral TH. CONCLUSION: Reduced FDG uptake in ipsilateral
      TH and contralateral CE usually occur simultaneously in patients with solitary
      brain tumors.

PMID- 29372377
TI  - Microarray profiles reveal that circular RNA hsa_circ_0007385 functions as an
      oncogene in non-small cell lung cancer tumorigenesis.
AB  - OBJECTIVE: Circular RNAs (circRNAs) are a novel class of non-protein-coding RNA.
      Emerging evidence indicates that circRNAs participate in the regulation of many
      pathophysiological processes. This study aims to explore the expression profiles
      and pathological effects of circRNAs in non-small cell lung cancer (NSCLC).
      METHODS: Human circRNAs microarray analysis was performed to screen the
      expression profile of circRNAs in NSCLC tissue. Expressions of circRNA and miRNA
      in NSCLC tissues and cells were quantified by qRTPCR. Functional experiments were
      performed to investigate the biological functions of circRNA, including CCK-8
      assay, colony formation assay, transwell assay and xenograft in vivo assay.
      RESULTS: Human circRNAs microarray revealed a total 957 abnormally expressed
      circRNAs (> twofold, P < 0.05) in NSCLC tissue compared with adjacent normal
      tissue. In further studies, hsa_circ_0007385 was significantly up regulated in
      NSCLC tissue and cells. In vitro experiments with hsa_circ_0007385 knockdown
      resulted in significant suppression of the proliferation, migration and invasion
      of NSCLC cells. In vivo xenograft assay using hsa_circ_0007385 knockdown,
      significantly reduced tumor growth. Bioinformatics analysis and luciferase
      reporter assay verified the potential target miR-181, suggesting a possible
      regulatory pathway for hsa_circ_0007385. CONCLUSION: In summary, results suggest
      hsa_circ_0007385 plays a role in NSCLC tumorigenesis, providing a potential
      therapeutic target for NSCLC.

PMID- 29372379
TI  - Effect on cerebral oxygenation of paracetamol for patent ductus arteriosus in
      preterm infants.
AB  - : Paracetamol seems to have similar success rates compared with indomethacin and
      ibuprofen in closing patent ductus arteriosus (PDA) in preterm infants, but with
      a better safety profile. The aim of our study was to evaluate the possible
      effects of paracetamol on cerebral oxygenation and cerebral blood flow velocity
      (CBFV). Infants with gestational age < 32 weeks with hemodynamically significant
      PDA (hsPDA) were prospectively studied by near infrared spectroscopy (NIRS) after
      the first dose of paracetamol (15 mg/kg) or ibuprofen (10 mg/kg). Cerebral
      regional oxygenation (rSO2C) and fractional oxygen extraction ratio (FOEC) were
      recorded 30 min before (T0) and 60 +/- 20 min (T1), 180 +/- 30 min (T2), and 360
      +/- 30 min (T3) after the beginning of drug infusion. Moreover, mean flow
      velocity (Vmean) and resistance index (RI = PSV-DV/PSV) measured with Doppler
      ultrasound in pericallosal artery were recorded at the same times. Significant
      changes in rSO2C and FOEC were not found during the study period within and
      between the groups. Similarly, Vmean did not vary in infants treated with
      paracetamol or ibuprofen, while RI decreased in the ibuprofen group. CONCLUSION:
      The treatment of hsPDA with paracetamol does not affect cerebral oxygenation in
      very preterm infants; there were no differences in cerebral oxygenation in
      infants treated with paracetamol or ibuprofen, although in the ibuprofen group,
      the possible closure progression of PDA was associated to changes of RI. What is
      Known: * Paracetamol has similar success rates to indomethacin and ibuprofen in
      closing PDA with a better safety profile since previous studies did not report
      adverse effects. What is New: * Paracetamol does not affect cerebral oxygenation
      and perfusion in very preterm infants with PDA and this confirms its good safety
      profile.

PMID- 29372380
TI  - Correlation between religion and hypertension.
AB  - The objectives of the study were to investigate the relationship between religion
      and hypertension, as well as the theoretical mechanism through which religion
      exerts effect on hypertension. A MEDLINE literature search was performed on
      articles describing religion and hypertension (N = 543) excluding unqualified
      ones such as those without expected information, those neither correcting
      confounding factors nor matching the comparison groups and those reporting
      repeated trials. Eight extra articles from references of reviews were added to
      the included studies. Finally, 79 articles were formerly evaluated. Briefly,
      there are limited trials on correlation between religion and hypertension and
      their results are inconsistent. First of all, longitudinal investigations,
      especially the high-quality ones, are deficient. Secondly, studies evaluating
      religion as an integral are scarce, although they can assess religions most
      comprehensively. Third, few studies use several religious measurements that
      represent distinct dimensions of religion. Moreover, divergence exists among
      diverse populations, even if they are assessed by the same indicator. In
      addition, 59% studies are concerned with an unspecified species of religion, and
      Christianity is studied the most among those with a specific category of
      religion. Finally, the possible mechanism underlying religion and hypertension is
      complex, which can partially explain the different results among various
      populations. Comprehensive evaluation of a specific religion should be
      encouraged. In addition, for a specific population, the correlation between
      religion and hypertension should be examined particularly, even if similar
      investigations in other populations have been conducted. Finally, more evidence
      focused on the effects of distinct religions/sects is also required.

PMID- 29372378
TI  - SYK-targeted dendritic cell-mediated cytotoxic T lymphocytes enhance the effect
      of immunotherapy on retinoblastoma.
AB  - PURPOSE: Retinoblastoma (RB) is the most common primary intraocular tumor in
      children. Chemotherapy is currently the main method of RB treatment.
      Unfortunately, RB often becomes chemoresistant and turns lethal. Here, we used in
      vitro cell immunotherapy to explore whether adoptive immunotherapy could be used
      as a potential treatment for RB. We focused on spleen tyrosine kinase (SYK),
      which is significantly upregulated in RB cells and serves as a marker for RB
      cells. METHODS: Using lentiviruses, we genetically modified dendritic cells (DCs)
      to express and present the SYK peptide antigen to cytotoxic T lymphocytes (CTLs)
      in vitro. We used SYK-negative cell lines (MDA-MB-231, MCF-10A, and hTERT-RPE1)
      and SYK-positive cell lines (MCF-7 and RB-Y79) to evaluate the specificity and
      cytotoxicity of DC presented CTLs using FACS, live-cell imaging, and RNA
      interference. RESULTS: The cytotoxicity of CTLs induced by SYK-overexpressing DCs
      (SYK-DC-CTLs) was enhanced more than three times in SYK-positive cell lines
      compared with SYK-negative cell lines. DCs primed with SYK could drive CTL
      cytotoxicity against SYK-positive cell lines but not against SYK-negative cell
      lines. Moreover, SYK-silenced RB-Y79 cells successfully evaded the cytotoxic
      attack from SYK-DC-CTLs. However, SYK-DC-CTLs could target SYK overexpressed
      hTERT-RPE1 cells, suggesting that SYK is a specific antigen for RB. Furthermore,
      SYK-DC-CTL exhibited specific cytotoxicity against carboplatin-resistant RB-Y79
      cells in vitro. CONCLUSIONS: Our data showed that SYK could be a potential
      immunotherapy target mediated by DCs. We propose SYK as a candidate target for
      treatment of chemoresistant RB.

PMID- 29372382
TI  - Comorbid insomnia and sleep apnea: a prevalent but overlooked disorder.

PMID- 29372381
TI  - Cloning and characterization of a specific UDP-glycosyltransferase gene induced
      by DON and Fusarium graminearum.
AB  - KEY MESSAGE: TaUGT5: can reduce the proliferation and destruction of F.
      graminearum and enhance the ability of FHB resistance in wheat. Deoxynivalenol
      (DON) is one of the most important toxins produced by Fusarium species that
      enhances the spread of the pathogen in the host. As a defense, the UDP
      glycosyltransferase (UGT) family has been deduced to transform DON into the less
      toxic form DON-3-O-glucoside (D3G), but the specific gene member in wheat that is
      responsible for Fusarium head blight (FHB) resistance has been little
      investigated and proved. In this study, a DON and Fusarium graminearum responsive
      gene TaUGT5, which is specific for resistant cultivars, was cloned with a 1431 bp
      open reading frame (ORF) encoding 476 amino acids in Sumai3. TaUGT5 is located on
      chromosome 2B, which has been confirmed in nulli-tetrasomic lines of Chinese
      Spring (CS) and is solely expressed among three homologs on the A, B and D
      genomes. Over-expression of this gene in Arabidopsis conferred enhanced tolerance
      when grown on agar plates that contain DON. Similarly, the coleoptiles of wheat
      over-expressing TaUGT5 showed more resistance to F. graminearum, evidencing
      reduced proliferation and destruction of plant tissue by the pathogen. However,
      the disease resistance in spikes was not as significant as that on coleoptile
      compared with wild-type plants. A subcellular localization analysis revealed that
      TaUGT5 was localized on the plasma membrane of tobacco leaf epidermal cells. It
      is possible that TaUGT5 could enhance tolerance to DON, protect the plant cell
      from the pathogen infection and result in better maintenance of the cell
      structure, which slows down pathogen proliferation in plant tissue.

PMID- 29372383
TI  - Surface IgM lambda light chain is involved in the binding and infection of
      infectious bursal disease virus (IBDV) to DT40 cells.
AB  - Infectious bursal disease virus (IBDV) is an important immunosuppressive virus in
      chickens. Surface immunoglobulin M (sIgM)-bearing B lymphocytes act as the major
      targets of IBDV in the bursa of Fabricius, and sIgM may function as one of the
      membrane binding sites responsible for IBDV infection. Recently, using the virus
      overlay protein binding assay, the chicken lambda light chain of sIgM was
      identified to specifically interact with IBDV in a virulence-independent manner
      in vitro. To further investigate sIgM lambda light chain-mediated IBDV binding
      and infection in pre-B cells, the cell line DT40, which is susceptible to both
      pathogenic and attenuated IBDV, was used. Based on the RNA interference strategy,
      the DT40 cell line whose lambda light chain of sIgM was stably knocked down,
      herein termed DT40LKD, was generated by the genomic integration of a specific
      small hairpin RNA and a green fluorescence protein co-expression construct. Flow
      cytometry analysis indicated that the binding of IBDV to DT40LKD cells was
      significantly reduced due to the loss of sIgM lambda light chain. In particular,
      reduced viral replication was observed in IBDV-incubated DT40LKD cells, and no
      viral release into cell culture medium was detected by the IBDV rapid diagnostic
      strips. In addition, the rescue of sIgM lambda light chain expression restored
      viral binding and replication in DT40LKD cells. These results show that sIgM
      lambda light chain appears to be beneficial for IBDV attachment and infection,
      suggesting that sIgM acts as a binding site involved in IBDV infection.

PMID- 29372384
TI  - Validation of the German version of the Kujala score in patients with
      patellofemoral instability: a prospective multi-centre study.
AB  - INTRODUCTION: The Kujala score is the most frequently used questionnaire for
      patellofemoral disorders like pain, instability or osteoarthritis. Unfortunately,
      we are not aware of a validated German version of the Kujala score. The aim of
      our study was the translation and linguistic validation of the Kujala score in
      German-speaking patients with patella instability and the assessment of its
      measurement characteristics. MATERIALS AND METHODS: The German Kujala score was
      developed in several steps of translation. In addition to healthy controls, the
      Kujala German was assessed in consecutive patients undergoing reconstruction of
      the medial patellofemoral ligament for recurrent patellar dislocations. Pre-op, 6
      and 12 months postop the patients completed the Kujala German score, the KOOS,
      the Lysholm score, a VAS Pain, and the SF-12v2 scores. In addition, there was a
      Kujala German Score retest preop after a 1-week interval. RESULTS: We found high
      reliability in terms of internal consistency for the Kujala score (Cronbach's
      alpha = 0.87). Convergent validity with the KOOS (symptom r = 0.65, pain r =
      0.78, ADL r = 0.74, sports/recreation r = 0.84, quality of life r = 0.70), the
      Lysholm score (r = 0.88) and the SF-12 physical component summary score (r =
      0.79) and VAS pain (r = - 0.71) was also very high. Discriminant validity in
      terms of correlation with the SF-12 mental component summary Score was
      satisfactory (r = 0.14). CONCLUSIONS: In conclusion, the German version of the
      Kujala score proved to be a reliable and valid instrument in the setting of a
      typical patellofemoral disease treated with a standard patellofemoral procedure.

PMID- 29372386
TI  - Comparison of sagittal values between lateral decubitus plain radiography and
      supine computed tomography in thoracolumbar fractures: a greater degree of
      kyphosis is observed in plain radiography than CT.
AB  - OBJECTIVE: Radiologic parameters are important factors for planning the treatment
      for thoracolumbar fracture. However, we noted that measurements of the degree of
      kyphosis by lateral decubitus plain radiography were greater than supine CT. The
      cause of this discrepancy is unclear. METHODS: We retrospectively reviewed the
      plain radiographs and CT scans of 90 patients with thoracolumbar fractures
      (fracture group). We measured the segmental sagittal angle (SSA) on lateral
      decubitus plain radiographs and in the median sagittal plane on CT scans obtained
      in the supine position. The method agreement (plain radiography versus CT) was
      determined by utilizing Bland-Altman plots. For the purpose of comparison, the
      same analyses were performed in a group of age and sex-matched controls (normal
      group). After establishing the method disagreement in the fracture group, the
      factors that contributed to the difference in the SSA between plain radiography
      and CT, as well as their threshold values, were determined. RESULTS: On Bland
      Altman plots for the fracture group, the mean difference was 4.53 degrees  [95%
      confidence interval (CI) - 4.87 degrees  to 13.93 degrees ]. For the normal
      group, the mean difference was - 0.64 degrees  (95% CI - 5.87 degrees  to 4.58
      degrees ). On univariate analysis, male sex, thoracolumbar level, and SSA(X) were
      significant factors associated with ?SSA (P = 0.03, 0.002, and 0.000,
      respectively). Multivariable regression analysis showed that SSA(X) was the only
      significant factor. Receiver operating characteristic curve analysis indicated
      that the optimal threshold of SSA(X) was 17 degrees  with a sensitivity of 78%
      and a specificity of 75% (area under curve: 0.752). CONCLUSIONS: The mean SSA
      determined on lateral decubitus plain radiographs indicated significantly more
      kyphosis than that determined on CT images obtained in supine position. When the
      SSA on plain radiography is more than 17 degrees , there might be a significant
      discrepancy between the two imaging modalities. This discrepancy seems to be
      mainly attributable to the difference in patient positioning (lateral decubitus
      position for plain radiography versus supine position for CT imaging).

PMID- 29372387
TI  - Myasthenia gravis and infectious disease.
AB  - BACKGROUND AND PURPOSE: Myasthenia gravis (MG) is an autoimmune disease with
      muscular weakness as the only symptom, and often with immunosuppressive
      treatment. All these aspects could have relevance for the risk of infections as
      well as their prophylactic and curative treatment. METHODS: This is a review
      article, where Web of Science has been searched for relevant key words and key
      word combinations. Full papers were selected first by title and then by abstract.
      RESULTS AND CONCLUSIONS: MG can be triggered and worsened by infections. No virus
      or other pathogen has been proven to have a specific link to MG. Treatment with
      immunosuppressive drugs and thymectomy implies a slightly increased risk for
      infections. Infections should be actively treated, but a few antibiotics are
      avoided due to potential interference with neuromuscular transmission.
      Hospitalization and intensive care may be necessary during infections because of
      MG deterioration and risk of insufficient respiration. Vaccinations are generally
      recommended in MG, but live microorganisms should be avoided if possible in
      immunosuppressed patients.

PMID- 29372389
TI  - Lothar von Frankl-Hochwart (1862-1914).

PMID- 29372388
TI  - Increased pro-inflammatory cytokine gene expression in peripheral blood
      mononuclear cells of patients with polyneuropathies.
AB  - BACKGROUND: Distinct cytokine expression patterns have been reported in
      biomaterial of patients with polyneuropathies (PNP). We investigated gene
      expression profiles of pro- and anti-inflammatory cytokines in peripheral blood
      mononuclear cells (PBMC) of patients with neuropathies of different etiologies.
      METHODS: We prospectively studied 97 patients with neuropathies and compared data
      between diagnostic subgroups and healthy controls. Gene expression of a panel of
      pro- and anti-inflammatory cytokines was analyzed (interleukin-1 [IL-1], IL-2, IL
      6, IL-8, tumor necrosis factor alpha [TNF], IL-4, and IL-10) in PBMC samples.
      Furthermore, protein levels of IL-6, IL-8, and TNF were measured in supernatant
      of PBMC stimulated with lipopolysaccharide (LPS). RESULTS: PNP were associated
      with higher PBMC gene expression of IL-1 (p < 0.05), IL-2 (p < 0.05), IL-8 (p <
      0.001), and TNF (p < 0.01) compared to healthy controls. Inflammatory
      neuropathies were associated with higher gene expression of IL-8 (p < 0.001) and
      TNF (p < 0.05) and lower gene expression of IL-10 (p < 0.05) compared to healthy
      controls. More pro-inflammatory cytokines were elevated in painful neuropathy (IL
      1, IL-2 [p < 0.05], IL-8 [p < 0.001] and TNF [p < 0.05]) than in painless
      neuropathy (IL-8 [p < 0.01] and TNF [p < 0.01]) compared to healthy controls,
      while IL-10 expression was higher in treatment naive patients with painless
      neuropathy compared to patients with painful neuropathy (p < 0.05). Disease
      duration positively correlated with IL-6 gene expression (p < 0.01). Supernatant
      protein levels of IL-6, IL-8, and TNF did not differ between groups. CONCLUSION:
      Systemic gene expression of pro-inflammatory cytokines is increased in patients
      with neuropathies and may be influenced by the presence of neuropathic pain.

PMID- 29372390
TI  - Impact of D-dimer levels for short-term or long-term outcomes in cryptogenic
      stroke patients.
AB  - BACKGROUND: D-dimer levels are used in several clinical settings, such as in
      predicting venous thrombosis, cardioembolic stroke and cancer status. In the
      present study, we investigated the associations between plasma D-dimer levels at
      admission, clinical characteristics and mortality at discharge in cryptogenic
      stroke patients. We also investigated whether D-dimer levels can predict long
      term outcomes in those patients, including those with and without right-to-left
      shunt (RLS). METHODS: Acute cryptogenic stroke patients (n = 295, 72 +/- 13 years
      old) were consecutively enrolled and retrospectively analyzed. We defined the
      cryptogenic stroke as an undetermined etiology according to the Trial of Org
      10172 in Acute Stroke Treatment criteria. Plasma D-dimer levels at admission were
      evaluated. Assessments for RLS were performed using saline contrast-transcranial
      Doppler ultrasonography or contrast-transesophageal echography. Survivors (at
      discharge) underwent follow-up for up to 3 years after stroke onset. RESULTS: Of
      the total enrolled cohort, 17 patients died at discharge. D-dimer levels
      correlated with initial National Institutes of Health Stroke Scale (NIHSS) score
      (r = 0.391, P < 0.001) and were associated with mortality at discharge [odds
      ratio 1.04; 95% confidence interval (CI) 1.00-1.08, P = 0.049] after adjusting
      for age, sex and initial NIHSS score. Of the 278 survivors at discharge, 266
      patients were evaluated to assess RLS during hospitalization, and 62 patients
      (23.3%) exhibited RLS. According to the median plasma D-dimer levels at admission
      (0.7 ug/ml), the patients were divided into a low D-dimer group (n = 136, <
      median) and a high D-dimer group (n = 130, >= median). Patients in the high D
      dimer group were older, more frequently female, had a lower BMI, had a higher
      prevalence of cancer and had greater initial neurological severity compared to
      the patients in the low D-dimer group. During the follow-up period (median, 1093
      days), 31 patients developed recurrent stroke and 33 patients died. High D-dimer
      levels at admission were independently associated with recurrent stroke and all
      cause mortality [hazard ratio (HR) 3.76; 95% CI 1.21-14.1, P = 0.021) in patients
      with RLS, but not in those without RLS (HR 1.35; 95% CI 0.74-2.50, P = 0.335).
      CONCLUSIONS: Increased D-dimer levels at admission were associated with mortality
      at discharge in cryptogenic stroke patients. In addition, high D-dimer levels
      were also associated with long-term outcomes in cryptogenic stroke patients with
      RLS.

PMID- 29372391
TI  - Genotype-phenotype correlation and frequency of distribution in a cohort of
      Chinese Charcot-Marie-Tooth patients associated with GDAP1 mutations.
AB  - Mutations in ganglioside-induced differentiation-associated-protein 1 (GDAP1)
      have been associated with both subtypes of Charcot-Marie-Tooth (CMT) disease,
      autosomal recessive (CMT4A and AR-CMT2K) and autosomal dominant (AD-CMT2K). Over
      80 different mutations have been identified so far. With the use of Sanger
      sequencing and Next Generation Sequencing (NGS) technologies, we screened a
      cohort of 306 unrelated Chinese CMT patients and identified 8 variants in the
      GDAP1 gene in 4 families, 5 of which were novel (R41H, N201Kfs*5, Q38X, V215I and
      Q38R). Application of Bioinformatics tool and classification according to the
      American College of Medical Genetics (ACMG) predicted them of being likely
      pathogenic with the exception of one variant of uncertain significance (VUS). In
      addition, we detected the presence of a single heterozygous variant of uncertain
      significance H256R in one additional family from the CMT cohorts. We found a
      GDAP1 prevalence rate of 1.63% (5/306). Three families (families 1, 2 and 3) were
      found to have an autosomal recessive (AR) pattern of inheritance while family 4
      displayed an autosomal dominant (AD) mode of inheritance. Electro-physiologic
      studies revealed an axonal type of neuropathy (AR-CMT2K and AD-CMT2K) in all
      affected individuals. Clinical characteristics and findings in our study
      demonstrated that the recessive form presented earlier in life and exhibited
      severe symptoms and rapid evolution compared to the dominant form. We observed a
      marked intra-familial variability within the AD family in terms of age at disease
      onset, symptom severity and clinical progression. Our study expands the
      mutational spectrum of GDAP1-related CMT disease with the identification of new
      and unreported GDAP1 variants and demonstrates the predominance of the axonal
      form of neuropathy in CMT disease associated with GDAP1. We highlight the
      clinical characteristics associated with these genotypes and describe the
      relative frequency of GDAP1 variants amongst the Chinese population.

PMID- 29372392
TI  - Management of nonfunctioning pituitary tumors: radiotherapy.
AB  - External beam radiotherapy (RT) is an essential part of the management of
      intracranial tumors and has been used in treating pituitary adenomas for more
      than five decades. It has been demonstrated that conventional RT for
      postoperative residual or progressive nonfunctioning pituitary adenomas (NFAs)
      present an excellent long-term local tumor control, although its use has been
      limited because of the potential late toxicity related to radiation treatments.
      Recent advances in radiation techniques have led to more accurate treatments,
      rendering obsolete many commonly held views of the "old" radiotherapy. New
      techniques include intensity modulated radiotherapy, volumetric-modulated arc
      therapy, and stereotactic techniques, either stereotactic radiosurgery or
      fractionated stereotactic radiotherapy. New techniques allow the delivering of
      higher radiation doses to the target with rapid dose fall-off in the surrounding
      normal tissues, and potentially limiting the long term toxicity of radiation. In
      this review, we present a critical analysis of the most recent available
      literature on the use of radiation in patients with NFAs, focusing particularly
      on the efficacy and safety of radiation stereotactic techniques.

PMID- 29372393
TI  - Approach to the Diagnostic Workup and Management of Small Bowel Lesions at a
      Tertiary Care Center.
AB  - BACKGROUND: Small bowel lesions (SBL) are rare, representing diagnostic and
      management challenges. The purpose of this cross-sectional study was to evaluate
      diagnostic modalities used and management practices of patients with SBL at an
      advanced endoscopic referral center. METHODS: We analyzed patients undergoing
      surgical management for SBL from 2005 to 2015 at a single tertiary care center.
      Patients were stratified into gastrointestinal bleed/anemia (GIBA) or
      obstruction/pain (OP). RESULTS: One hundred and twelve patients underwent surgery
      after presenting with either GIBA (n = 67) or OP (n = 45). The mean age of our
      study population was 61.8 years and 45% were women. Patients with GIBA were more
      likely to have chronic or acute-on-chronic symptoms (100% vs 67%) and more often
      referred from outside hospitals (82 vs. 44%) (p < 0.01). The most common
      preoperative imaging modalities were video capsule endoscopy (VCE) (96%) for GIBA
      and computer tomography CT (78%) for OP. Findings on VCE and CT were most
      frequently concordant with operative findings in GIBA (67%) and OP (54%)
      patients, respectively. Intraoperatively, visual inspection or palpation of the
      bowel successfully identified lesions in 71% of patients. When performed in GIBA
      (n = 26), intraoperative enteroscopy (IE) confirmed or identified lesions in 69%
      of patients. Almost all (90%) GIBA patients underwent small bowel resections;
      most were laparoscopic-assisted (93%). Among patients with OP, 58% had a small
      bowel resection and the majority (81%) were laparoscopic-assisted. Surgical
      exploration failed to identify lesions in 10% of GIBA patients and 24% of OP
      patients. Among patients who underwent resections, 20% of GIBA patients had
      recurrent symptoms compared with 13% of OP patients. CONCLUSION: Management and
      identification of SBL is governed by presenting symptomatology. Optimal
      management includes VCE and IE for GIBA and CT scans for OP patients.
      Comprehensive evaluation may require referral to specialized centers.

PMID- 29372394
TI  - Financial and socio-economic factors influencing pre- and post-cancer therapy
      oral care.
AB  - PURPOSE: The primary objective of this study is to evaluate how attendance at
      dental visits may change as cancer patients move through pre-diagnosis,
      diagnosis, and into survivorship. METHODS: The Health and Retirement Study
      consists of longitudinal survey data collected biannually detailing financial and
      health information in subjects over 51 years old. We assessed a subset of 4195
      patients who received a new cancer diagnosis during the study period. The odds of
      reporting a dental visit were examined using a mixed effects logistic regression
      model. A propensity score weighted analysis of the association between dental
      attendance and survival was also undertaken. RESULTS: The odds of attending a
      dental visit were substantially lower in the peri-diagnosis period OR = 0.784
      (0.700, 0.876) and the post-diagnosis period OR = 0.734 (0.655, 0.823) compared
      to pre-diagnosis. This effect persisted in patients who survived for at least 2
      years indicating that the decline in oral health visits was not due to low
      expected survival. After propensity score weighting, patients who attended a
      dental visit in the peri-diagnosis period demonstrated a reduced hazard of all
      cause mortality HR = 0.825 (0.681, 0.979) compared with those with no attendance.
      CONCLUSIONS: Dental attendance decreases by a statistically and clinically
      significant amount both during and after cancer therapy despite guideline
      recommendations encouraging dental referral and monitoring for many types of
      cancer therapy. Attendance at dental appointments during cancer therapy is
      associated with improved survival, which is likely due to a combination of direct
      and indirect effects.

PMID- 29372395
TI  - Impaired skeletal muscle oxygenation following allogeneic hematopoietic stem cell
      transplantation is associated with exercise capacity.
AB  - INTRODUCTION: Impaired skeletal muscle oxygenation potentially contributes to
      reduced exercise capacity in allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) patients during early recovery and may explain altered hemoglobin
      responses to exercise following allo-HSCT. We investigated whether skeletal
      muscle oxygenation parameters and hemoglobin parameters in the tibialis anterior
      decreased following allo-HSCT, and whether these results were associated with
      declines in exercise capacity. METHODS: We used near-infrared spectroscopy during
      and following a repeated isometric contraction task at 50% of maximal voluntary
      contraction in 18 patients before and after allo-HSCT. RESULTS: The rate of
      decrease in the muscle oxy-hemoglobin saturation (SmO2; an index of skeletal
      muscle oxygenation) was significantly lower after allo-HSCT (P < 0.01). In
      contrast, total hemoglobin (an index of hemoglobin) was not different after allo
      HSCT. Furthermore, SmO2 during and following exercise was associated with
      exercise capacity (r = 0.648; P = 0.004 vs. r = 0.632; P = 0.005). CONCLUSION:
      The results of this study reveal that although the peripheral hemoglobin response
      was not altered by allo-HSCT, skeletal muscle oxygenation was decreased following
      allo-HSCT. Furthermore, the decrease in skeletal muscle oxygenation was
      associated with a reduction in exercise capacity.

PMID- 29372396
TI  - Symptom management: the utility of regional cooling for hand-foot syndrome
      induced by pegylated liposomal doxorubicin in ovarian cancer.
AB  - PURPOSE: Hand-foot syndrome (HFS) is a major side effect of pegylated liposomal
      doxorubicin (PLD). Regional cooling during PLD infusion was shown to improve
      severe HFS. We investigated the utility of frozen gloves and socks (FGS) as a
      simpler cooling method. METHODS: To evaluate the utility and safety of regional
      cooling with FGS for PLD-induced HFS, we retrospectively analyzed patients with
      advanced ovarian cancer who used FGS during PLD-containing regimens. RESULTS:
      Ninety-six patients were analyzed. The incidence of HFS was 51% (>= grade 2, 32%)
      in the PLD group and 38% (>= grade 2, 6%) in the PLD + CBDCA group. The
      respective percentages of patients who underwent PLD dose
      modification/discontinuation were 41%/75% in the PLD group and 9%/30% in the PLD
      + CBDCA group. The reasons for discontinuation of PLD and PLD + CBDCA therapy
      were progressive disease, HFS, allergy, oral mucositis, and others. HFS was the
      only reason for PLD dose modification in both the PLD and PLD + CBDCA groups. The
      completion rate of FGS was 96%, with discontinuation in three cases due to pain
      from cooling. CONCLUSIONS: Our study indicates that FGS is a safe, simple method
      with good tolerability. A prospective study is needed for further assessment.

PMID- 29372397
TI  - Aortic root remodeling in a patient with Turner syndrome using the reference
      curves of aortic diameters in children.
AB  - We report the successful surgical treatment of aortic regurgitation in a 27-year
      old woman with Turner syndrome (TS) who was admitted with exacerbation of dyspnea
      on exertion. Echocardiography showed a bicuspid aortic valve with severe aortic
      regurgitation and computed tomography showed dilatation of the ascending aorta
      and aortic root. Due to the patient's low body surface area (due to TS), standard
      determination of aortic size was not possible; therefore, we used the reference
      curves of aortic diameters in children. Because of the possibility of fatal
      ascending aortic dissection and rupture, we performed concomitant aortic root
      remodeling and aortic valve repair.

PMID- 29372398
TI  - Transapical approach in transcatheter cardiovascular interventions.
AB  - The left ventricular apex has excellent accessibility to the aortic valve, mitral
      valve, left ventricular outflow tract and thoracic aorta. Although the number of
      transapical approach in transcatheter aortic valve replacement has been
      decreasing in recent years, it is still a useful option for patients with very
      poor peripheral vascular access. The apex has been chosen as a primary access
      site for many devices of transcatheter mitral valve repair/replacement and mitral
      valve-in-valve procedures. Additionally, the transapical approach has been used
      for other transcatheter cardiovascular interventions such as paravalvular leak
      repair after mitral or aortic valve replacement, pseudoaneurysm repair of the
      left ventricular outflow tract, and thoracic endovascular aortic repair. Herein,
      I review our own experience and articles of the transapical transcatheter
      cardiovascular interventions and discuss about clinical usability, technical tips
      and complications of the transapical approach in various transcatheter
      cardiovascular interventions.

PMID- 29372399
TI  - Does my patient have a pulmonary embolism? The Wells vs. PISA 2 rule in
      orthopedic patients.
AB  - The diagnosis of venous thromboembolism is difficult in the postoperative setting
      because signs such as hypoxemia, leg pain, and swelling are so common. CTPA can
      also detect subsegmental PE (SSPE), of which the clinical significance has been
      widely debated. Clinical decision rules (CDR), such as the Wells and PISA 2, have
      been developed to identify symptomatic patients at low risk for PE who could
      forgo imaging. We performed this study in order to (1) compare the performance of
      the Wells and PISA 2 CDR in orthopedic patients; (2) compare CDR scores in
      patients with subsegmental PE (SSPE) versus larger clots; and (3) identify
      variables that improve performance of the Wells in orthopedic patients. This
      retrospective cohort study included all orthopedic surgery patients that
      underwent computerized tomographic pulmonary angiography at a single institution
      from 1/1/13 to 12/31/14 and had data to calculate both Wells and PISA 2 scores.
      CDR sensitivity, specificity and c-statistics were calculated. Multivariable
      logistic regression was used to identify variables that improved CDR performance.
      402 patients were included in the study. The Wells rule (cutoff > 4) had
      sensitivity 74% and specificity 45%. PISA 2 (cutoff 0.6) had sensitivity 90% and
      specificity 11%. The Wells performed better than PISA 2: c-statistic 0.60 vs.
      0.50; p = 0.007. The mean Wells score was 5.20 +/- 1.68 for patients with SSPE
      and 5.41 +/- 1.86 for patients with larger clots. Adding the variables prior
      smoking and varicose veins improved the performance of the Wells rule (c
      statistic 0.66 vs. 0.60, p = 0.008). The Wells rule (cutoff > 4) performs better
      than PISA 2 in orthopedic patients. Neither can distinguish patients with SSPE
      from those with larger clots. Although adding past smoking and varicose veins to
      the Wells improves its performance, this requires validation in other
      populations.

PMID- 29372400
TI  - Andexanet alfa to reverse the anticoagulant activity of factor Xa inhibitors: a
      review of design, development and potential place in therapy.
AB  - Direct oral anticoagulants are associated with rates of major bleeding which are
      not negligible, albeit lower than those associated with vitamin K antagonists. No
      specific reversal agent for factor Xa (FXa) direct inhibitors is currently
      available for clinical use. A modified activated human FXa decoy protein,
      andexanet alfa, is being developed that binds FXa direct inhibitors in their
      active site, thus reversing their anticoagulant effect. The purpose of this
      article is to review the design, development and clinical trials of andexanet
      alfa. Andexanet alfa was shown to reverse FXa inhibitors anticoagulant activity
      both in thrombosis animal models, healthy volunteers and patients with acute
      major bleeding. Andexanet alfa has been studied in double-blind, placebo
      controlled phase II and III studies. A preliminary report of the phase III study
      showed that an effective hemostasis was obtained after andexanet alfa infusion in
      the majority of the patients with acute major bleeding associated with FXa
      inhibitors. Additional studies are ongoing and andexanet alfa is expected to be
      launched in the market in the near future.

PMID- 29372401
TI  - Exosomes in Extracellular Matrix Bone Biology.
AB  - PURPOSE OF REVIEW: Exosomes are membrane vesicles that are released by most cell
      types into the extracellular environment. The purpose of this article is to
      discuss the main morphological features and contents of bone-derived exosomes, as
      well as their major isolation and physical characterization techniques.
      Furthermore, we present various scenarios and discuss potential clinical
      applications of bone-derived exosomes in bone repair and regeneration. RECENT
      FINDINGS: Exosomes were believed to be nanosized vesicles derived from the
      multivesicular body. Reports now suggest that nanovesicles could bud directly
      from the plasma membrane. However, the exosome cargo is cell-type specific and is
      derived from the parent cell. In the bone matrix, several intracellular proteins
      lacking a signal peptide are transported to the ECM by exosomes. Besides
      proteins, several mRNA, miRNA, and lipids are exported to the ECM by bone cells
      and bone marrow stromal cells. Recent evidence suggests that several of the
      functional components in the cargo could regulate processes of bone formation,
      inhibit osteoclast activity, and promote fracture repair. Exosomes are powerful
      cellular molecular machines produced without human intervention and packaged with
      physiological cargo that could be utilized for molecular therapy in several
      skeletal disorders such as osteoporosis, osteogenesis imperfecta, and fracture
      healing. Although much work has been done, there is a lot of information that is
      still unknown, as exosomes contain a multitude of molecules whose identity and
      function have yet to be identified.

PMID- 29372402
TI  - Intraoperative intravenous fluorescein as an adjunct during surgery for peroneal
      intraneural ganglion cysts.
AB  - The intraoperative use of intravenous fluorescein is presented in a case of
      peroneal intraneural ganglion cyst. When illuminated with the operative
      microscope and yellow filter, this fluorophore provided excellent visualization
      of the abnormal cystic peroneal nerve and its articular branch connection. The
      articular (synovial) theory for the pathogenesis of intraneural cysts is further
      supported by this pattern of fluorescence. Further, our report presents a novel
      use of fluorescein in peripheral nerve surgery.

PMID- 29372403
TI  - There Is no Ideal Bariatric Procedure.

PMID- 29372404
TI  - Problems of classification in the family Paramyxoviridae.
AB  - A number of unassigned viruses in the family Paramyxoviridae need to be
      classified either as a new genus or placed into one of the seven genera currently
      recognized in this family. Furthermore, numerous new paramyxoviruses continue to
      be discovered. However, attempts at classification have highlighted the
      difficulties that arise by applying historic criteria or criteria based on
      sequence alone to the classification of the viruses in this family. While the
      recent taxonomic change that elevated the previous subfamily Pneumovirinae into a
      separate family Pneumoviridae is readily justified on the basis of RNA dependent 
      RNA polymerase (RdRp or L protein) sequence motifs, using RdRp sequence
      comparisons for assignment to lower level taxa raises problems that would require
      an overhaul of the current criteria for assignment into genera in the family
      Paramyxoviridae. Arbitrary cut off points to delineate genera and species would
      have to be set if classification was based on the amino acid sequence of the RdRp
      alone or on pairwise analysis of sequence complementarity (PASC) of all open
      reading frames (ORFs). While these cut-offs cannot be made consistent with the
      current classification in this family, resorting to genus-level demarcation
      criteria with additional input from the biological context may afford a way
      forward. Such criteria would reflect the increasingly dynamic nature of virus
      taxonomy even if it would require a complete revision of the current
      classification.

PMID- 29372405
TI  - Molecular analysis of barley stripe mosaic virus isolates differing in their
      biological properties and the development of reverse transcription loop-mediated
      isothermal amplification assays for their detection.
AB  - Barley stripe mosaic virus (BSMV) is an important seed-transmitted pathogen
      occurring worldwide. Recently, the occurrence of mild BSMV pathotypes has been
      observed in barley crops in Poland. In this study, the full-length genome
      sequences of mild and aggressive Polish and German BSMV isolates was established.
      Phylogenetic and recombination analysis was performed using Polish and other BSMV
      isolates described to date. The analysis revealed that Polish isolates differed
      only in 25 nucleotides, which suggests that point mutations might have had a
      great impact on the biological properties of the virus. The phylogenetic analysis
      revealed that the closest relationship was that between European and BSMV-CV42,
      BSMV-ND18 and BSMV-Type isolates, whereas the highest genetic distance was
      observed for BSMV-Qasr Ibrim and BSMV-China isolates. A recombination event
      within the alphaa protein of BSMV-De-M and BSMV-CV42 isolates was also detected.
      Moreover, a sensitive reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) method was developed for rapid detection of BSMV
      isolates. The RT-LAMP assay can be used for routine diagnostics of BSMV in seed
      and plant material.

PMID- 29372406
TI  - Evidence for a complex of emergent poleroviruses affecting pepper worldwide.
AB  - In recent years, symptoms of vein yellowing and leaf roll in pepper crops
      associated with the presence of poleroviruses (genus Polerovirus, family
      Luteoviridae) have been emerging in many countries worldwide. Spain was the first
      country in Europe where the yellowing disease of pepper was observed. In this
      work, a polerovirus isolate from Spain that infects pepper and has been shown to
      be transmitted by the aphid Aphis gossyppii (Spain-Almeria 2-2013) was sequenced
      and compared with isolates from Japan, Israel, China and Australia. The genome
      (6125 nt in length, GenBank accession number KY523072) of the isolate from Spain
      has the typical organization of poleroviruses and contains seven open reading
      frames (ORF0 to ORF5 and ORF3a), putatively encoding proteins P0 to P5 and P3a. A
      comparison of the sequence from Spain with the four complete sequences available
      for poleroviruses infecting pepper showed a closer relationship to the isolate
      from Israel and supports the existence of a complex of at least five polerovirus
      species. Given that the symptoms caused by all pepper poleroviruses described to
      date are similar, if not identical, we propose to name them "pepper vein yellows
      virus 1" to "pepper vein yellows virus 5" (PeVYV-1 to PeVYV-5), with PeVYV-5
      corresponding to the polerovirus from Spain described in this work. Our results
      and those published over the last few years have shown that the emergent
      poleroviruses threatening pepper crops around the world are highly complex due to
      recombination events.

PMID- 29372407
TI  - Stroke chameleon (cortical hand syndrome) in a patient with moderate carotid
      stenosis: a neurological double-trouble.

PMID- 29372408
TI  - Ectomycorrhizal inoculation with Pisolithus tinctorius reduces stress induced by
      drought in cork oak.
AB  - We investigated whether the performance of cork oak under drought could be
      improved by colonization with the ectomycorrhizal fungus Pisolithus tinctorius.
      Results show that inoculation alone had a positive effect on plant height, shoot
      biomass, shoot basal diameter, and root growth. Under drought, root growth of
      mycorrhizal plants was significantly increased showing that inoculation was
      effective in increasing tolerance to drought. In accordance, mycorrhizal plants
      subjected to drought showed less symptoms of stress when compared to non
      mycorrhizal plants, such as lower concentration of soluble sugars and starch,
      increased ability to maintain fatty acid content and composition, and increased
      unsaturation level of membrane lipids. After testing some of the mechanisms
      suggested to contribute to the enhanced tolerance of mycorrhizal plants to
      drought, we could not find any by which Pisolithus tinctorius could benefit cork
      oak, at least under the drought conditions imposed in our experiment. Inoculation
      did not increase photosynthesis under drought, suggesting no effect in sustaining
      stomatal opening at low soil water content. Similarly, plant water status was not
      affected by inoculation suggesting that P. tinctorius does not contribute to an
      increased plant water uptake during drought. Inoculation did increase nitrogen
      concentration in plants but it was independent of the water status. Furthermore,
      no significant mycorrhizal effect on drought-induced ROS production or osmotic
      adjustment was detected, suggesting that these factors are not important for the
      improved drought tolerance triggered by P. tinctorius.

PMID- 29372409
TI  - Do doctors understand the test characteristics of lung cancer screening?
AB  - BACKGROUND: Screening for lung cancer with a low-dose computed tomography (CT)
      scan is estimated to prevent 3 deaths per 1000 individuals at high risk; however,
      false positive results and radiation exposure are relevant harms and deserve
      careful consideration. Screening candidates can only make an autonomous decision
      if doctors correctly inform them of the pros and cons of the method; therefore,
      this study aimed to evaluate whether doctors understand the test characteristics
      of lung cancer screening. METHODS: In a randomized trial 556 doctors (members of
      the Austrian Respiratory Society) were invited to answer questions regarding lung
      cancer screening based on online case vignettes. Half of the participants were
      randomized to the group 'solutions provided' and received the correct solutions
      in advance. The group 'solutions withheld' had to rely on prior knowledge or
      estimates. The primary endpoint was the between-group difference in the estimated
      number of deaths preventable by screening. Secondary endpoints were the between
      group differences in the prevalence of lung cancer, prevalence of a positive
      screening results, sensitivity, specificity, positive predictive value, and false
      negative rate. Estimations were also compared with current data from the
      literature. RESULTS: The response rate was 29% in both groups. The reduction in
      the number of deaths due to screening was overestimated six-fold (95% confidence
      interval CI: 4-8) compared with the actual data, and there was no effect of group
      allocation. Providing the correct solutions to doctors had no systematic effect
      on their answers. CONCLUSION: Doctors poorly understand the test characteristics
      of lung cancer screening. Providing the correct solutions in advance did not
      improve the answers. Continuing education regarding lung cancer screening and the
      interpretation of test characteristics may be a simple remedy. CLINICAL TRIAL
      REGISTRATION: Clinical trial registered with www.clinicaltrials.gov
      (NCT02542332).

PMID- 29372410
TI  - Assessing serum albumin concentration, lymphocyte count and prognostic
      nutritional index might improve prognostication in patients with myelofibrosis.
AB  - BACKGROUND: Primary and secondary myelofibrosis (PMF and SMF) are malignant
      diseases of hematopoietic stem cell characterized by the neoplastic
      myeloproliferation and a strong inflammatory milieu. The prognostic nutritional
      index (PNI) integrates information on albumin and absolute lymphocyte count (ALC)
      and reflects the inflammatory, nutritional and immune status of a patient. The
      clinical and prognostic significance of albumin, ALC and PNI in patients with
      myelofibrosis has not been previously investigated. METHODS: We retrospectively
      analyzed a cohort of 83 myelofibrosis patients treated in our institution from
      2006 to 2017. Albumin, ALC and PNI were assessed in addition to other disease
      specific markers. RESULTS: The PMF and SMF patients had significantly lower ALC
      and PNI but similar albumin compared to controls. Lower albumin was significantly
      associated with older age and parameters reflecting more aggressive disease
      biology (e.g. anemia, lower platelet levels, higher lactate dehydrogenase (LDH),
      circulatory blasts, transfusion dependency, blast phase disease), inflammation
      (higher C reactive protein (CRP), constitutional symptoms) and higher degree of
      bone marrow fibrosis. Lower ALC was significantly associated with lower white
      blood cells (WBC) and lower circulatory blasts. Low PNI was associated with lower
      albumin, lower ALC, anemia, lower WBCs, lower serum iron and lower transferrin
      saturation. There was no difference in albumin, ALC and PNI regarding the driver
      mutations. In multivariate analysis adjusted for age and gender, low albumin
      (hazard ratio [HR] = 4.61, P = 0.001), low ALC (HR = 3.54, P = 0.004) and Dynamic
      International Prognostic Scoring System (DIPSS) (HR = 2.45, P = 0.001) were able
      to predict inferior survival independently of each other. Accordingly, low PNI
      (HR = 4.32, P < 0.001) predicted poor survival independently of DIPSS (HR = 3.31,
      P < 0.001). CONCLUSION: Assessing albumin, ALC and PNI might improve
      prognostication in patients with myelofibrosis and could assist in recognition of
      patients under increased risk of death.

PMID- 29372411
TI  - [S1 guideline - Austrian consensus for anticoagulation in the context of atrial
      fibrillation ablation].
AB  - In summary, uninterrupted oral antikoagulation can be recommended, with different
      recommendation classes and levels of evidence, for both, VKA and NOAC therapy, in
      the framework of PVI. Even with low CHA2DS2 VASc scores, OAK is indicated 3-4
      weeks before and 8 weeks after the procedure. Periinterventional bridging with
      heparins should be avoided due to increased bleeding events.The present Consensus
      provides recommendations on the current state of knowledge and has been prepared
      exclusively by members of the Rhythmology Working Group of the Austrian
      Cardiological Society who have great practical experience in catheter ablation
      and peri-interventional OAK in patients with atrial fibrillation. Publication of
      new randomized and controlled studies on the subject are expected in the coming
      months, so that there will certainly be changes in the recommendations. The
      Rhythmology Working Group of the Austrian Cardiological Society will strive to
      keep this S1 guideline regularly up to date. We hope that this consensus is used
      to increase the safety for patients undergoing PVI and to provide physicians with
      a homogeneous approach in Austria.

PMID- 29372412
TI  - The effect of in situ simulation training on the performance of tasks related to
      patient safety during sedation.
AB  - In many countries, procedural sedation outside of the operating room is performed
      by pediatricians. We examined if in situ sedation simulation training (SST) of
      pediatricians improves the performance of tasks related to patient safety during
      sedation in the Emergency Department (ED). We performed a single-center, quasi
      experimental, study evaluating the performance of sedation, before-and-after SST.
      Sixteen pediatricians were evaluated during sedation as part of their usual
      practice, using the previously validated Sedation-Performance-Score (SPS). This
      tool evaluates physician behaviors during sedation that are conducive to safe
      patient outcomes. Following the sedation, providers completed SST, followed by a
      structured debriefing. They were then re-evaluated with the SPS during a
      subsequent patient sedation in the ED. Using multivariate regression, odds ratios
      were calculated for each SPS component, and were compared before and after the
      SST. Thirty-two sedations were performed, 16 before and 16 after SST. SPS scores
      improved from a median of 4 (IQR 2-5) to 6 (IQR 4-7) following SST (p < 0.0009,
      median difference 2, 95% CI 1-3). SST was associated with improved performance in
      four SPS components. The findings of this pilot study suggest that sedation
      simulation training of pediatricians improves several tasks related to patient
      safety during sedation.

PMID- 29372413
TI  - Persistent isoflurane-induced hypotension causes hippocampal neuronal damage in a
      rat model of chronic cerebral hypoperfusion.
AB  - BACKGROUND: Postoperative cognitive dysfunction (POCD) is likely to occur in
      elderly people, who often suffer from cerebral hypoperfusion and white matter
      lesions even in the absence of cerebral infarctions. METHODS: Thirty-two adult
      male rats were randomly assigned to one of four groups: the cerebral
      normoperfusion + normotension group (n = 8), cerebral normoperfusion +
      hypotension group (n = 8), chronic cerebral hypoperfusion (CCH) + normotension
      group (n = 8), and CCH + hypotension group (n = 8). A rat model of CCH was
      developed via the permanent ligation of the bilateral common carotid arteries,
      but ligation was avoided in the cerebral normoperfusion groups. Two weeks later,
      the rats were intubated and mechanically ventilated under isoflurane anesthesia,
      and their mean arterial blood pressure was maintained over 80 mmHg (normotension)
      or below 60 mmHg (hypotension) for 2 h. After preparing brain slices,
      histological cresyl violet staining, ionized calcium binding adaptor molecule 1,
      a marker of microglial activation, or beta amyloid precursor protein, a marker of
      axonal damage, were performed. RESULTS AND CONCLUSION: CCH per se caused
      microglial activation and axonal damage, which was not accentuated by
      hypotension. CCH alone did not cause neuronal damage, but CCH combined with
      hypotension caused significant neuronal damage in the hippocampal CA1 region.
      These results suggest that persistent hypotension during general anesthesia might
      cause neuronal damage in patients with CCH, such as elderly people, and
      contribute to prevention against POCD.

PMID- 29372414
TI  - Changes of the phytoplankton community as symptoms of deterioration of water
      quality in a shallow lake.
AB  - Covering more than 60% of the lake surface, macrophytes determined the taxonomic
      composition of phytoplankton. We have found numerous indications of ecological
      deterioration and an increased trophic level year to year: an increased total
      number of taxa; a significantly increased number of species of Chlorophyta,
      Bacillariophyceae and Cyanoprokaryota; a decreased number of Chrysophyceae;
      increased Nygaard index, and high diversity and variability of phytoplankton
      functional groups. Within 2 years (2002 and 2003) algal biomass doubled: from
      3.616 to 7.968 mg l-1. An increased contribution of Chlorococcales and
      Cyanoprokaryota indicates progressive eutrophication of the lake. The average
      size of planktonic algae increased, particularly Cyanoprokaryota, where small
      celled decreased dramatically and were replaced by large colonies.
      Cyanoprokaryota remained the dominant group of phytoplankton after 10 years, and
      the ecosystem of the lake remained in the turbid state. This group of algae had
      the average biomass 9.734 mg l-1, which constituted almost 92% of the total
      biomass.

PMID- 29372415
TI  - Presenting a conceptual pattern of HSE performance of oil trucks.
AB  - Accidents are among the main problems in the oil product supply chain. The most
      important effective factors in these events are the kind of trucks used and their
      health, safety, and environment (HSE) condition. The aim of this study was to
      present a conceptual pattern of the HSE performance of oil trucks in oil
      industries. In this study, 20 truck models (with fixed tanks), in use over
      different periods of time, were investigated. In this regard, the criteria and
      sub-criteria were first determined in two parts-carrier and tank-and weighted by
      fuzzy analytical hierarchy process (FAHP). The results showed that the most
      important sub-criteria regarding the HSE factors of the carrier were resistance
      and strength of the front and rear shields, the brake system, and the ventilation
      system. The most important sub-criteria regarding the HSE factors of the tank
      were tank shell thickness and a good tank design shape with respect to portable
      material. It should be noted that the weight of the criteria with each other and
      sub-criteria with each other are not equal. This issue is important for decision
      making. The main reason for the use of trucks with the lowest score in developing
      countries is the lack of attention by managers to safety issues and international
      standards and agreements such as the ADR.

PMID- 29372416
TI  - Galectin-3 regulation of wound healing and fibrotic processes: insights for
      chronic skin wound therapeutics.
AB  - A member of the lectin family, galectin-3 is a 250 amino-acid protein that
      contains a C-terminus carbohydrate recognition domain (CRD) that recognizes beta
      galactosides. Considered to have certain common properties associated with
      matricellular proteins, galectin-3 is expressed in the dermis and epidermis in
      healthy skin and is upregulated in skin healing, peaking at day 1 post wounding
      in mice. Galectin-3 has been implicated in several processes central to the wound
      healing response, specifically in the regulation of inflammation, macrophage
      polarization, angiogenesis, fibroblast to myofibroblast transition and re
      epithelialization. However, it appears that many of the effects of Galectin-3 are
      highly tissue specific and context dependent. Genetic deletion of galectin-3
      shows different effects in skin compared to lung, heart, and kidney remodeling.
      In this review, we will compare galectin-3 functions in these tissues.
      Furthermore, we will discuss, based on its identified regulation of cell
      processes, whether in an exogenous form, galectin-3 could represent a novel
      therapeutic for impaired skin healing.

PMID- 29372418
TI  - Tyrosine Residues 232 and 401 Play a Critical Role in the Binding of the Cofactor
      FAD of Acyl-coA Oxidase.
AB  - Acyl-coA oxidase (ACO) is an important flavoenzyme responsible for the first step
      of peroxisomal fatty acid beta-oxidation. In this study, the roles of Tyr232 and
      Tyr401 in flavin adenine dinucleotide (FAD) binding and enzyme catalysis of ACO
      were explored using site-directed mutagenesis. For mutant proteins, different
      levels of activity loss were observed. Wavelength scanning of Y232 and Y401
      mutant proteins indicated that there is no FAD binding in Y401S and Y401G mutant
      ACO. Structure analysis indicated that the phenolic hydroxyl and benzene ring of
      the side chain could stabilize FAD binding through hydrogen bonds network and
      hydrophobic pocket formation. These results indicated that these two tyrosine
      residues play a critical role in the FAD binding of ACO.

PMID- 29372417
TI  - Effect of obesity on outcomes in patients undergoing implantation of continuous
      flow left ventricular assist devices.
AB  - The purpose of this study was to analyze the effect of obesity on outcomes after
      continuous-flow left ventricular assist device (CF-LVAD) implantation. A single
      center retrospective analysis was performed on 526 chronic heart failure patients
      who were implanted with the HeartMate II CF-LVAD (n = 403) or HeartWare HVAD (n =
      123) between November 2003 and March 2016. Patients were stratified into 4 groups
      based on BMI: underweight (< 18.5 kg/m2, n = 18, 3.4%), normal-weight (18.5-25
      kg/m2, n = 173, 32.9%), overweight (25-30 kg/m2, n = 182, 30.2%), and obese (> 30
      kg/m2, n = 153, 33.5%). The underweight group was excluded because of its small
      sample size. Records were reviewed to determine the incidence of postoperative
      complications and survival. Survival at 1, 6, 12, and 24 months were similar
      among normal-weight (91.3, 84.4, 76.3, and 67.6%), overweight (90.4, 80.8, 76.5,
      and 69.6%), and obese patients (90.7, 74.7, 65.3, and 61.3%, p = 0.24).
      Additionally, obesity was not a significant predictor of mortality in Cox
      proportional hazard models (hazard ratio 0.98, 95% confidence interval 0.766
      1.277, p = 0.13). These findings suggest that appropriately selected obese
      patients receive similar survival benefit from CF-LVADs compared to non-obese
      patients, and obesity should not serve as a contraindication to CF-LVAD
      implantation.

PMID- 29372419
TI  - Anti-Hypertensive Peptides Derived from Caseins: Mechanism of Physiological
      Action, Production Bioprocesses, and Challenges for Food Applications.
AB  - This review is focused on the state-of-art of peptides with inhibitory activity
      towards angiotensin I-converting enzyme (ACE) - thus, with anti-hypertensive
      potential - derived from enzymatic hydrolysis of caseins. Firstly, molecular
      characteristics of caseins relevant to a better understanding of this subject
      were concisely commented. Next, a brief description of the pathophysiology of
      hypertension was explained, focusing on the ACE role in regulation of blood
      pressure in human body. Then, casein-derived peptides with ACE inhibitory
      capacity were specifically addressed. The main in vitro and in vivo bioassays
      often reported in literature to assess the anti-hypertensive potential of
      peptides were presented, illustrated with recently published studies, and
      discussed in terms of advantages and limitations of both approaches.
      Characteristics related to amino acid composition and sequence of peptides with
      high ACE-inhibitory potential were also commented. Process parameters of
      enzymatic hydrolysis (types and origins of casein substrates, types of enzymes,
      pH, temperature, and times of reactions) were discussed. Patents dealing with
      casein-derived anti-hypertensive peptides were examined not only in terms of
      amino acid sequences, but also regarding their novelty claims in hydrolysis
      process parameters. Finally, some trends, challenges, and opportunities inferred
      from this literature analysis were commented, emphasizing the importance of this
      research topic in food products development.

PMID- 29372420
TI  - Reusable Software Usability Specifications for mHealth Applications.
AB  - One of the key factors for the adoption of mobile technologies, and in particular
      of mobile health applications, is usability. A usable application will be easier
      to use and understand by users, and will improve user's interaction with it. This
      paper proposes a software requirements catalog for usable mobile health
      applications, which can be used for the development of new applications, or the
      evaluation of existing ones. The catalog is based on the main identified sources
      in literature on usability and mobile health applications. Our catalog was
      organized according to the ISO/IEC/IEEE 29148:2011 standard and follows the SIREN
      methodology to create reusable catalogs. The applicability of the catalog was
      verified by the creation of an audit method, which was used to perform the
      evaluation of a real app, S Health, application created by Samsung Electronics
      Co. The usability requirements catalog, along with the audit method, identified
      several usability flaws on the evaluated app, which scored 83%. Some flaws were
      detected in the app related to the navigation pattern. Some more issues related
      to the startup experience, empty screens or writing style were also found. The
      way a user navigates through an application improves or deteriorates user's
      experience with the application. We proposed a reusable usability catalog and an
      audit method. This proposal was used to evaluate a mobile health application. An
      audit report was created with the usability issues identified on the evaluated
      application.

PMID- 29372421
TI  - Different Digitalization Techniques for 3D Printing of Anatomical Pieces.
AB  - The use of different technological devices that allow the creation of three
      dimensional models is in constant evolution, allowing a greater application of
      these technologies in different fields of health sciences and medical training.
      The equipment for digitalization is becoming increasingly sophisticated allowing
      obtaining three-dimensional which are more defined and similar to real image and
      original object. In this work, different modalities of designing 3D anatomical
      models of bone pieces are presented, for use by students of different disciplines
      in Health Sciences. To do this we digitalized bone pieces, with different models
      of scanners, producing images that can be transformed for 3D printing, with a
      Colido X 3045 printer by digital treatment with different software.

PMID- 29372422
TI  - Socioeconomic and Health Profile of Haitian Immigrants in a Brazilian Amazon
      State.
AB  - We analyzed the sociodemographic profile, migration journey, health conditions,
      and health care access and utilization among recent Haitian immigrants to the
      Brazilian Amazon state of Mato Grosso. We conducted a cross-sectional study with
      a probabilistic sample of 452 Haitians. We administered a bilingual questionnaire
      from December 2014 to February 2015. Data were analyzed using chi square tests to
      evaluate differences among groups. The majority of participants were married men
      younger than 35 years old. They mostly came from the Haiti's Artibonite
      Department, living in Brazil for less than a year. Half of the participants were
      employed at the time of the interviews, and 81.8% relied exclusively on the
      Brazilian Unified Healthcare System for medical care. The overall health profile
      and health care access were good. Haitian migration to Brasil is a case of South
      South migration driven by economic needs. Our population had good health status
      despite socioeconomic challenges.

PMID- 29372423
TI  - Nocardioides astragali sp. nov., isolated from a nodule of wild Astragalus
      chrysopterus in northwestern China.
AB  - A Gram-positive, non-motile, rod-shaped bacterial strain, designated HH06T, was
      isolated from a nodule of Astragalus chrysopterus in northwestern China.
      Phylogenetic analysis of the 16S rRNA gene sequence showed that the strain is
      closely related to Nocardioides alpinus Cr7-14T and Nocardioides furvisabuli DSM
      18445T with 98.5 and 98.1% similiarity, respectively. Growth was observed at 4-28
      degrees C in R2A medium (optimum at 25  degrees C), at 10-30  degrees C in YMA
      and LB medium (optimum in both at 28  degrees C) and at pH 5.0-10.0 in R2A medium
      (optimum at pH 7.0-8.0). The cell wall peptidoglycan was found to contain LL
      diaminopimelic acid as the principal diamino acid and MK-8(H4) was identified as
      the predominant menaquinone. The major polar lipids were identified as
      phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol,
      phosphatidylcholine, two unidentified glycolipids and two unidentified polar
      lipids. The major fatty acids were identified as iso-C16:0 (32.8%) and C18:1
      omega9c (15.1%). The DNA G+C content of strain HH06T was determined to be 71.4
      mol%. Based on phenotypic, chemotaxonomic, phylogenetic properties and DNA-DNA
      relatedness, it is concluded that strain HH06T represents a novel species of the
      genus Nocardioides, for which the name Nocardioides astragali sp. nov. is
      proposed. The type strain is HH06T (= CGMCC 4.7327T = NBRC 112322T).

PMID- 29372424
TI  - A possible mechanism for lincomycin induction of secondary metabolism in
      Streptomyces coelicolor A3(2).
AB  - Lincomycin forms cross-links within the peptidyl transferase loop region of the
      23S ribosomal RNA (rRNA) of the 50S subunit of the bacterial ribosome, which is
      the site of peptide bond formation, thereby inhibiting protein synthesis. We have
      previously reported that lincomycin at concentrations below the minimum
      inhibitory concentration potentiates the production of secondary metabolites in
      actinomycete strains, suggesting that activation of these strains by utilizing
      the dose-dependent response of lincomycin could be used to effectively induce the
      production of cryptic secondary metabolites. Here, we aimed to elucidate the
      fundamental mechanisms underlying lincomycin induction of secondary metabolism in
      actinomycetes. In the present study, the dose-dependent response of lincomycin on
      gene expression of the model actinomycete Streptomyces coelicolor A3(2) and
      possible relationships to secondary metabolism were investigated. RNA sequencing
      analysis indicated that lincomycin produced enormous changes in gene expression
      profiles. Moreover, reverse transcription PCR and/or comparative proteome
      analysis revealed that in S. coelicolor A3(2), lincomycin, which was used at
      concentrations for markedly increased blue-pigmented antibiotic actinorhodin
      production, rapidly enhanced expression of the gene encoding the lincomycin
      efflux ABC transporter, the 23S rRNA methyltransferase, and the ribosome
      splitting factor to boost the intrinsic lincomycin resistance mechanisms and to
      reconstruct the probably stalled 70S ribosomes with lincomycin; and in contrast
      temporarily but dramatically reduced mRNA levels of housekeeping genes, such as
      those encoding FoF1 ATP synthase, RNA polymerase, ribosomal proteins, and
      transcription and translation factors, with an increase in intracellular NTPs. A
      possible mechanism for lincomycin induction of secondary metabolism in S.
      coelicolor A3(2) is discussed on the basis of these results.

PMID- 29372425
TI  - Effects of humic substances on Fe(II) sorption onto aluminum oxide and clay.
AB  - We studied the effects of humic substances (HS) on the sorption of Fe(II) onto Al
      oxide and clay sorbents at pH 7.5 with a combination of batch kinetic experiments
      and synchrotron Fe K-edge EXAFS analyses. Fe(II) sorption was monitored over the
      course of 4 months in anoxic clay and Al-oxide suspensions amended with variable
      HS types (humic acid, HA; or fulvic acid, FA) and levels (0, 1, and 4 wt%), and
      with differing Fe(II) and HS addition sequences (co-sorption and pre-coated
      experiments, where Fe(II) sorbate was added alongside and after HS addition,
      respectively). In the Al-oxide suspensions, the presence of HS slowed down the
      kinetics of Fe(II) sorption, but had limited, if any, effect on the equilibrium
      aqueous Fe(II) concentrations. EXAFS analyses revealed precipitation of Fe(II)
      Al(III)-layered double hydroxide (LDH) phases as the main mode of Fe(II) sorption
      in both the HA-containing and HA-free systems. These results demonstrate that HS
      slow down Fe(II) precipitation in the Al-oxide suspensions, but do not affect the
      composition or stability of the secondary Fe(II)-Al(III)-LDH phases formed.
      Interference of HS with the precipitation of Fe(II)-Al(III)-LDH was attributed to
      the formation organo-Al complexes HS limiting the availability of Al for
      incorporation into secondary layered Fe(II)-hydroxides. In the clay systems, the
      presence of HA caused a change in the main Fe(II) sorption product from Fe(II)
      Al(III)-LDH to a Fe(II)-phyllosilicate containing little structural Al. This was
      attributed to complexation of Al by HA, in combination with the presence of
      dissolved Si in the clay suspension enabling phyllosilicate precipitation. The
      change in Fe(II) precipitation mechanism did not affect the rate of Fe(II)
      sorption at the lower HA level, suggesting that the inhibition of Fe(II)-Al(III)
      LDH formation in this system was countered by enhanced Fe(II)-phyllosilicate
      precipitation. Reduced rates of Fe(II) sorption at the higher HA level were
      attributed to surface masking or poisoning by HA of secondary Fe(II) mineral
      growth at or near the clay surface. Our results suggest that HS play an important
      role in controlling the kinetics and products of Fe(II) precipitation in reducing
      soils, with effects modulated by soil mineralogy, HS content, and HS properties.
      Further work is needed to assess the importance of layered Fe(II) hydroxides in
      natural reducing environments.

PMID- 29372427
TI  - Prelude to "Pediatric and Congenital Heart Disease".

PMID- 29372426
TI  - From lake to estuary, the tale of two waters: a study of aquatic continuum
      biogeochemistry.
AB  - The balance of fresh and saline water is essential to estuarine ecosystem
      function. Along the fresh-brackish-saline water gradient within the C-43
      canal/Caloosahatchee River Estuary (CRE), the quantity, timing and distribution
      of water, and associated water quality significantly influence ecosystem
      function. Long-term trends of water quality and quantity were assessed from Lake
      Okeechobee to the CRE between May 1978 and April 2016. Significant changes to
      monthly flow volumes were detected between the lake and the estuary which
      correspond to changes in upstream management. and climatic events. Across the 37
      year period, total phosphorus (TP) flow-weighted mean (FWM) concentration
      significantly increased at the lake; meanwhile, total nitrogen (TN) FMW
      concentrations significantly declined at both the lake and estuary headwaters.
      Between May 1999 and April 2016, TN, TP, and total organic carbon (TOC), ortho-P,
      and ammonium conditions were assessed within the estuary at several monitoring
      locations. Generally, nutrient concentrations decreased from upstream to
      downstream with shifts in TN/TP from values > 20 in the freshwater portion, ~ 20
      in the estuarine portion, and < 20 in the marine portion indicating a spatial
      shift in nutrient limitations along the continuum. Aquatic productivity analysis
      suggests that the estuary is net heterotrophic with productivity being negatively
      influenced by TP, TN, and TOC likely due to a combination of effects including
      shading by high color dissolved organic matter. We conclude that rainfall
      patterns, land use, and the resulting discharges of runoff drive the ecology of
      the C-43/CRE aquatic continuum and associated biogeochemistry rather than water
      management associated with Lake Okeechobee.

PMID- 29372428
TI  - Cryosurgery in the excision of a giant local recurrent sacral chordoma: a case
      report and literature review.
AB  - PURPOSE: Chordoma is a low-grade malignant tumor with recurrence and metastasis
      tendency that originates from embryonic notochordal remnants. The sacrococcygeal
      region is the most commonly involved site. The aim of this paper is to report the
      results of the use of cryosurgery in the excision of a giant recurrent sacral
      chordoma and review of pertinent literature. METHODS: A 64 years old female
      patient with a locally recurrent sacral chordoma came to our attention after ten
      interventions performed at another institute. A surgical treatment was performed
      using argon cryosurgery. RESULTS: In this case, it was not possible to perform a
      marginal or wide excision, but it was intralesional with the removal of three
      major blocks. The fragments sent for the histological analysis measured total 35
      * 30 * 8 cm with a weight of 4.260 g. CONCLUSIONS: Given the gelatinous structure
      of the tumor and the possibility of contamination of operatory field, cryosurgery
      may be indicated when previous surgeries and the dimensions of tumor mass do not
      allow a resection with negative margins improving radiotherapy efficacy in the
      local control of tumor.

PMID- 29372429
TI  - Exploring traditional aus-type rice for metabolites conferring drought tolerance.
AB  - BACKGROUND: Traditional varieties and landraces belonging to the aus-type group
      of rice (Oryza sativa L.) are known to be highly tolerant to environmental
      stresses, such as drought and heat, and are therefore recognized as a valuable
      genetic resource for crop improvement. Using two aus-type (Dular, N22) and two
      drought intolerant irrigated varieties (IR64, IR74) an untargeted metabolomics
      analysis was conducted to identify drought-responsive metabolites associated with
      tolerance. RESULTS: The superior drought tolerance of Dular and N22 compared with
      the irrigated varieties was confirmed by phenotyping plants grown to maturity
      after imposing severe drought stress in a dry-down treatment. Dular and N22 did
      not show a significant reduction in grain yield compared to well-watered control
      plants, whereas the intolerant varieties showed a significant reduction in both,
      total spikelet number and grain yield. The metabolomics analysis was conducted
      with shoot and root samples of plants at the tillering stage at the end of the
      dry-down treatment. The data revealed an overall higher accumulation of N-rich
      metabolites (amino acids and nucleotide-related metabolites allantoin and
      uridine) in shoots of the tolerant varieties. In roots, the aus-type varieties
      were characterised by a higher reduction of metabolites representative of
      glycolysis and the TCA cycle, such as malate, glyceric acid and glyceric acid-3
      phosphate. On the other hand, the oligosaccharide raffinose showed a higher fold
      increase in both, shoots and roots of the sensitive genotypes. The data further
      showed that, for certain drought-responsive metabolites, differences between the
      contrasting rice varieties were already evident under well-watered control
      conditions. CONCLUSIONS: The drought tolerance-related metabolites identified in
      the aus-type varieties provide a valuable set of protective compounds and an
      entry point for assessing genetic diversity in the underlying pathways for
      developing drought tolerant rice and other crops.

PMID- 29372430
TI  - Emergency physician use of tissue Doppler bedside echocardiography in detecting
      diastolic dysfunction: an exploratory study.
AB  - INTRODUCTION: This study evaluates the agreement between emergency physician (EP)
      assessment of diastolic dysfunction (DD) by a simplified approach using average
      peak mitral excursion velocity (e'A) and an independent cardiologist's diagnosis
      of DD by estimating left atrial (LA) pressure using American Society of
      Echocardiography (ASE) guidelines. METHODS: This was a secondary analysis of 48
      limited bedside echocardiograms (LBE) performed as a part of a research study of
      patients presenting to the Emergency Department (ED) with elevated blood pressure
      but without decompensated heart failure. EPs diagnosed DD based on e'A < 9 cm/s
      alone. A blinded board-certified cardiologist reviewed LBEs to estimate LA
      filling pressures following ASE guidelines. An unweighted kappa measure was
      calculated to determine agreement between EP and cardiologist. RESULTS: Six LBEs
      were deemed indeterminate by the cardiologist and excluded from the analysis.
      Agreement was reached in 41 out of 48 cases (85.4%). The unweighted kappa
      coefficient was 0.74 (95% CI 0.57-0.92). EPs identified 18 out of 20 LBEs
      diagnosed with diastolic dysfunction by the cardiologist. CONCLUSION: There is a
      good agreement between (e'A) by EP and cardiologist interpretation of LBEs.
      Future studies should investigate this simplified approach as a one-step method
      of screening for LV diastolic dysfunction in the ED.

PMID- 29372432
TI  - When it looks and walks like an ant.
AB  - Some jumping spiders (family Salticidae) bear a striking resemblance to ants, a
      dangerous type of prey, both in terms of their appearance and in terms of how
      they move. Recent research has taken important steps toward determining whether
      predators categorize these spiders as ants on the basis of the way they move.

PMID- 29372433
TI  - The heterologous expression of Arabidopsis PAP2 induces anthocyanin accumulation
      and inhibits plant growth in tomato.
AB  - Anthocyanins are naturally occurring secondary metabolites, responsible for the
      color of many plants. The Arabidopsis thaliana MYB90/PAP2 (production of
      anthocyanin pigment 2) was introduced into tomato to study its effect on
      anthocyanin accumulation. The transgenic tomato displayed much greater
      anthocyanin accumulation than wild type in all plant organs, but the organs were
      not fully purple in color except for the stamen. The expression of anthocyanin
      biosynthetic genes and an anthocyanin-related basic helix-loop-helix (bHLH) gene
      SlAN1 was significantly increased in the transgenic line, suggesting that ectopic
      expression of AtPAP2 increases the expression of anthocyanin-related structural
      and regulatory genes to enhance anthocyanin content. Yeast two-hybrid assays
      revealed that the endogenous MYB protein SlAN2 interacted with two putative bHLH
      partners, SlAN1 and SlJAF13, while AtPAP2 only interacted with SlJAF13, which may
      be why AtPAP2 transgenic plants showed limited anthocyanin accumulation in
      fruits. In addition to anthocyanin accumulation, the transgenic tomato plants
      were significantly smaller in size, and the length of primary roots and number of
      lateral roots were obviously decreased. The expression of lignin biosynthetic
      genes was downregulated in transgenic tomato plants, which may be the reason for
      the inhibited growth. The lateral organ boundaries-domain (LBD) genes, which
      regulate lateral root organogenesis in the auxin signaling pathway, were
      downregulated in transgenic tomato roots, which may partly account for the
      disturbed lateral root formation in the transformants. Taken together, the
      results demonstrate that heterologous expression of transcription factor AtPAP2
      not only resulted in anthocyanin accumulation but also inhibited plant growth in
      tomato.

PMID- 29372434
TI  - Linearization of excitatory synaptic integration at no extra cost.
AB  - In many theories of neural computation, linearly summed synaptic activation is a
      pervasive assumption for the computations performed by individual neurons.
      Indeed, for certain nominally optimal models, linear summation is required.
      However, the biophysical mechanisms needed to produce linear summation may add to
      the energy-cost of neural processing. Thus, the benefits provided by linear
      summation may be outweighed by the energy-costs. Using voltage-gated conductances
      in a relatively simple neuron model, this paper quantifies the cost of
      linearizing dendritically localized synaptic activation. Different combinations
      of voltage-gated conductances were examined, and many are found to produce
      linearization; here, four of these models are presented. Comparing the energy
      costs to a purely passive model, reveals minimal or even no additional costs in
      some cases.

PMID- 29372435
TI  - Trunk Reaction Time and Kinematic Changes Following Slip Perturbations in
      Subjects with Recurrent Low Back Pain.
AB  - Postural responses following slip perturbations are critical to fall prevention
      strategies. It is unclear how postural reactions with a handheld task can validly
      be transferred to treadmill-induced slip perturbations in subjects with recurrent
      low back pain (LBP). The purpose of this study was to investigate trunk reaction
      times and trunk flexion angle as well as velocity following the slips between
      subjects with and without LBP. There were 29 subjects with LBP and 40 control
      subjects who participated in the study. Three levels of consecutive treadmill
      induced slip perturbations were introduced at level 1 (duration: 0.10 s,
      velocity: 0.24 m/s, displacement: 1.20 cm), level 2 (0.12 s, 0.72 m/s, 4.32 cm),
      and level 3 (0.12 s, 1.37 m/s, 8.22 cm). The trunk reaction time, swing/step
      times, and trunk flexion angle as well as velocity at heel strike/toe-off were
      compared between the groups. There were significantly longer trunk reaction times
      (t = - 2.03, p = 0.04), swing times (t = - 2.63, p = 0.01), and step times (t = -
      2.53, p = 0.01) in the LBP group at the level 1 slip perturbation. The groups
      demonstrated a significant interaction between the levels and trunk flexion
      angles (F = 4.72, p = 0.03), but there was no interaction between the levels and
      trunk flexion velocities (F = 0.07, p = 0.79). The LBP group demonstrated longer
      reaction times at the level 1 perturbation due to a possible pain recurrence.
      However, this compensatory tolerance was limited at the level 3 perturbation due
      to increased trunk flexion angle at heel strike and toe-off in the LBP group.
      Clinicians may consider a compensatory strategy to improve reaction time and
      minimize trunk flexion following slip perturbations in patients with LBP.

PMID- 29372437
TI  - Breast Milk Iodine Concentration Rather than Maternal Urinary Iodine Is a
      Reliable Indicator for Monitoring Iodine Status of Breastfed Neonates.
AB  - There is no scientific consensus on whether breast milk iodine concentration
      (BMIC) accurately reflects iodine status in lactating mothers and breastfed
      infants. This study aimed to compare BMIC and maternal urinary iodine
      concentration (UIC) as indicators of iodine status in breastfed neonates. In this
      cross-sectional study, 147 lactating mothers and their neonates (3-5 days
      postpartum) were randomly selected from health care centers. Breast milk and
      urine samples were collected from each mother and neonate, and a heel-prick blood
      sample was taken from all neonates as part of a congenital hypothyroidism
      screening program. According to the World Health Organization criteria, median
      urinary iodine concentration (UIC) >= 100 MUg/L in lactating mothers and neonates
      indicates iodine sufficiency. In areas of iodine sufficiency, median BMIC >= 100
      MUg/L is considered an adequate level. Overall, 129 (89.0%) and 16 (11.0%)
      mothers had BMICs >= 100 and ? 100 MUg/L, respectively. Median (interquartile
      range [IQR]) maternal UIC was 70 MUg/L (42-144 MUg/L) and 37 MUg/L (25-100 MUg/L)
      in mothers with breast milk iodine levels >= 100 and ? 100 MUg/L, respectively (P
      = 0.047); values for UIC of neonates born to mothers with BMICs >= 100 and ? 100
      MUg/L were 230 MUg/L (114-310 MUg/L) and 76 MUg/L (41-140 MUg/L), respectively (P
      < 0.001). In the linear regression model, neonate UIC was positively associated
      with BMIC in both unadjusted (beta = 0.558, P < 0.001) and adjusted analysis
      (beta = 0.541, P < 0.001). A similar result was found in logistic regression
      analysis, indicating that neonates born to mothers with BMIC >= 100 MUg/L were
      more likely to have UIC >= 100 MUg/L compared to those whose mothers had BMIC <
      100 MUg/L in both unadjusted (OR = 7.93, P < 0.001) and adjusted analysis (OR =
      7.29, P = 0.001). The present findings indicate that BMIC is a more sensitive
      indicator than maternal UIC for assessment of iodine status in breastfed
      neonates. To address low levels of maternal UIC, further studies on the
      prescription of supplements containing 150 MUg/day iodine during lactation period
      are warranted.

PMID- 29372436
TI  - Antioxidant and Cytoprotective Activity of Oxydiacetate Complexes of Cobalt(II)
      and Nickel(II) with 1,10-Phenantroline and 2,2'-Bipyridine.
AB  - The antioxidant properties of oxydiacetate complexes of cobalt(II) and nickel(II)
      with 1,10-phenantroline and 2,2'-bipyridine have been investigated towards the
      superoxide radical using the nitro blue tetrazolium chloride (NBT) test and the
      cyclic voltammetry (CV). Moreover, the biological activity of the complexes under
      study has been investigated in the Human Dermal Fibroblasts adult (HDFa) cell
      line. In the first step, the cytotoxic and the antiproliferative activities of
      the complexes were examined. Subsequently, the cytoprotective properties of the
      complexes have been investigated in an oxidative stress conditions induced by
      H2O2.

PMID- 29372438
TI  - Health-related quality of life of survivors of childhood acute lymphoblastic
      leukemia: a systematic review.
AB  - PURPOSE: Acute lymphoblastic leukemia (ALL) survivors are the largest group of
      childhood cancer survivors; however, their risk for late effects is high. Cancer
      related late effects have the potential to compromise health-related quality of
      life (HRQL) long into survivorship. None of the reviews so far have focused on
      ALL solely, but described HRQL for all childhood cancers. We aimed to identify
      ALL survivors at risk for poor HRQL and identify possible risk factors. METHOD:
      Following PRISMA guidelines, we performed a systematic review, searching
      published literature in Pubmed, PsycInfo, Embase, and the Cochrane database
      including all publications up to December 16, 2016. Two independent reviewers (JV
      and ER) screened eligible articles and assessed article quality. RESULTS: We
      found 31 studies representing 4356 survivors and 901 proxies. Thirteen studies
      found worse, eight found no difference, and three better, overall HRQL scores
      compared with healthy controls or norms. ALL survivors typically had better
      overall HRQL scores than survivors of other childhood cancers. Clinical variables
      (e.g., treatment received) were not consistently associated with HRQL; however,
      experiencing worse late effects was associated with lower HRQL. Survivor and
      parent socio-demographic factors and psychological factors such as resilience and
      depression were also associated with HRQL. CONCLUSION: ALL survivors appeared to
      have worse or equivalent HRQL compared with controls, but better HRQL than
      survivors of other cancer types. However, studies reported a wide variability in
      HRQL and potential risk factors for poor HRQL. Measuring ALL survivors' HRQL
      longitudinally and comprehensively assessing potential risk factors might
      identify future avenues to intervene early.

PMID- 29372439
TI  - Antioxidant activity of polyphenolic compounds isolated from ethyl-acetate
      fraction of Acacia hydaspica R. Parker.
AB  - BACKGROUND: Acacia hydaspica belongs to family leguminosae possess antioxidant,
      anti-inflammatory and anticancer activities. During our search for antioxidant
      compounds from A. hydaspica, we carried out bioassay guided fractionation and
      obtained antioxidant compounds with free radical scavenging activity. MATERIALS
      AND METHODS: The polyphenol compounds in the plant extract of A. hydaspica were
      isolated by combination of different chromatographic techniques involving vacuum
      liquid chromatography and medium pressure liquid chromatography. The structural
      heterogeneity of isolated compounds was characterized by high pressure liquid
      chromatography, MS-ESI and NMR spectroscopic analyses. The antioxidant potential
      of isolated compounds has been investigated by 1,1-diphenyl-2-picrylhydrazyl
      (DPPH), nitric oxide scavenging potential, hydroxyl radical scavenging potential,
      ferric reducing/antioxidant power (FRAP) model systems and total antioxidant
      capacity measurement. RESULTS: The isolated compounds show the predominance of
      signals representative of 7-O-galloyl catechins, catechins and methyl gallate.
      Flash chromatographic separation gives 750 mg of 7-O galloyl catechin, 400 mg of
      catechin and 150 mg of methyl gallate from 4 g loaded fraction on ISCO. Results
      revealed that C1 was the most potent compound against DPPH (EC50 1.60 +/- 0.035
      uM), nitric oxide radical (EC50 6 +/- 0.346 uM), showed highest antioxidant index
      (1.710 +/- 0.04) and FRAP [649.5 +/- 1.5 uM Fe(II)/g] potency at 12.5 uM dose
      compared to C2, C3 and standard reference, whereas C3 showed lower EC50 values
      (4.33 +/- 0.618 uM) in OH radical scavenging assay. CONCLUSION: Present research
      reports for the first time the antioxidant activity of polyphenolic compounds of
      A. hydaspica. Result showed good resolution and separation from other
      constituents of extract and method was found to be simple and precise. The
      isolation of catechin from this new species could provide a varied opportunity to
      obtain large quantities of catechin and catechin isomers beside from green tea.
      Free radical scavenging properties of isolated catechin isomers from A. hydaspica
      merit further investigations for consumption of this plant in oxidative stress
      related disorders.

PMID- 29372440
TI  - Erratum to: Current status of development of anticancer agents in Japan.

PMID- 29372441
TI  - A new species of Steringotrema Odhner, 1911 (Trematoda: Fellodistomidae) from the
      New Zealand sole Peltorhamphus novaezeelandiae Gunther off Kaka point in the
      Catlins, South Island, New Zealand.
AB  - As a part of a comprehensive survey of macroparasites of commercially exploited
      fish species off the coast of Otago, New Zealand, the parasite fauna of the New
      Zealand sole Peltorhamphus novaezeelandiae Gunther was recently studied.
      Steringotrema robertpoulini n. sp. is described from this host and compared with
      known species of Steringotrema Odhner, 1911. The new species is readily
      distinguished from all of its congeners, except for S. divergens (Rudolphi, 1809)
      Odhner, 1911, by having the follicular vitellarium divided in four zones rather
      than two, and can be differentiated from S. divergens mainly by the posterior
      extent of the intestinal caeca in the hindbody, as well as by host association
      and geographical distribution. DNA sequences of the 28S ribosomal gene were
      generated and phylogenetic analyses were undertaken using maximum likelihood and
      Bayesian inference to assess the phylogenetic position of the new species within
      the family Fellodistomidae Nicoll, 1909. Analyses included the available
      sequences for 14 species of the family distributed among eight genera, along with
      nine species of other members of the order Plagiorchiida La Rue, 1957 as
      outgroups. The resulting topology shows that the new species of Steringotrema is
      nested as the sister species of Steringophorus dorsolineatus (Reimer, 1985) Bray,
      1995. However, low nodal support indicates that relationships among these species
      are not fully resolved and require further revision and denser taxon sampling for
      more detailed molecular work. More information is required to draw further
      conclusions about the taxonomic status of the genera Steringotrema and
      Steringophorus Odhner, 1905.

PMID- 29372442
TI  - Two new species of Haplorchoides Chen, 1949 (Digenea: Heterophyidae) infecting an
      Australian siluriform fish, Neoarius graeffei Kner & Steindachner.
AB  - Combined morphological and molecular analyses are used to characterise two new
      species of Haplorchoides Chen, 1949 (Digenea: Heterophyidae) from an Australian
      siluriform fish. Haplorchoides maiwariensis n. sp. and H. daguilarensis n. sp.
      are described from the intestine of the Blue salmon catfish, Neoarius graeffei
      (Kner & Steindachner) (Siluriformes: Ariidae) from tidal reaches of the Brisbane
      River and from a freshwater creek off Lake Wivenhoe, Kipper Creek, Australia. The
      two new species most obviously differ from all previously described species of
      Haplorchoides in possessing clearly and reliably tripartite seminal vesicles. The
      two new species differ in the size and distribution of vitelline follicles, the
      size of the pigment granules and the form of the ventral sucker. Previously
      described species of Haplorchoides have been reported from Africa and Asia,
      principally from bagrid, schilbeid, silurid and sisorid catfishes; these are the
      first species reported from an ariid catfish. Complete ITS2 and partial 28S
      ribosomal DNA data were generated for both new species. The two species differ
      from each other by eight base pairs in the ITS2 region, and by 13 bp for the 28S
      region. The 28S rDNA sequence of H. daguilarensis agrees with a previously
      reported sequence from an unidentified species of Haplorchoides collected from N.
      graeffei in Lake Wivenhoe, Australia; we identify this previous report as
      relating to H. daguilarensis.

PMID- 29372443
TI  - Sensitivity of caries pathogens to antimicrobial peptides related to caries risk.
AB  - OBJECTIVES: Antimicrobial peptides (AMPs) represent important facets of the
      immune system controlling infectious diseases. However, pathogens show varying
      susceptibilities to AMPs. This study investigates the susceptibilities of strains
      of Streptococcus mutans (SM), Actinomyces naeslundii (AN), and Lactobacillus spp.
      (LB) towards AMPs and if there are correlations between the appearance of such
      high-risk strains and clinical caries status. MATERIAL AND METHODS: Plaque
      samples were collected from patients along with clinical examinations. Bacterial
      strains were identified via selective media, matrix-assisted laser
      desorption/ionization analysis-time of flight (MALDI-TOF), and arbitrary-primed
      PCR (AP-PCR). Each strain was tested for susceptibility to LL-37, HBD-2, HNP-1,
      and HNP-3 or phosphate-buffered saline as negative control in a biofilm model on
      hydroxylapatite discs. Survival rates and resulting risk classification for each
      strain were determined. Correlations were calculated between the number of high
      risk strains (all/S. mutans) appearing in patients and their clinical caries
      status. RESULTS: Forty-seven patients were included with mean DMFT values of 11.4
      +/- 8.7. A total of 8 different SM, 30 LB, and 47 AN strains were detected. One
      way ANOVA indicated that type/concentration of AMPs had major influence on
      reductions of Lactobacilli and Actinomyces. Seventeen strains of AN, 2 of SM, and
      6 of LB had low susceptibilities to AMPs. The number of such strains in patients
      showed significant positive correlations to the DMFT values (all p = 0.001; r =
      0.452; S. mutans p < 0.0001, r = 0.558). CONCLUSION: The occurrence of low
      susceptible strains to AMPs seems to correlate with the individual caries status.
      CLINICAL RELEVANCE: The results may lead to new ways to identify individuals with
      increased caries risk.

PMID- 29372444
TI  - Distance between mandibular canal and third molar root among 20-year-old
      subjects.
AB  - OBJECTIVES: The aim of the study was to evaluate the proximity of the mandibular
      third molar (M3) and the inferior alveolar canal (IAC) in a panoramic radiograph
      of 20-year-old subjects. The specific aim was to assess differences in this
      proximity over time. MATERIALS AND METHODS: Two similar samples of panoramic
      radiographs taken in a routine oral health examination with 20-year time interval
      were examined retrospectively and images with both mandibular M3s were included.
      The material consisted of 300 subjects (25% men, mean age 20.5 +/- 0.6 years).
      The radiographic relationship between the mandibular M3 root and the IAC was
      assessed as follows: the M3 root was either apart from, tangential to,
      superimposed with, or inferior to the IAC. Differences between frequencies were
      tested using the chi-squared test. RESULTS: In the combined samples, only 16% of
      the M3s located apart from the IAC, 15% located tangential to, 61% superimposed
      with, and 8% inferior to the IAC. The proportion of the intimate locations had
      increased during the 20-year time interval from 79 to 88% (P < 0.01) and
      especially in females (P < 0.05). CONCLUSION: The vast majority of the mandibular
      M3s situated very close to the mandibular canal. CLINICAL RELEVANCE: Our results
      suggest that in the cohort of 20-year-old non-extraction subjects, most of the
      M3s are possibly at risk for inferior alveolar nerve injury at removal, as judged
      from the panoramic radiograph, and also the number of such teeth has increased
      over the 20-year period.

PMID- 29372446
TI  - A web-based endodontic case difficulty assessment tool.
AB  - OBJECTIVE: To develop a web-based tool to facilitate identification, evaluation
      and management of teeth requiring endodontic treatment. MATERIALS AND METHODS:
      Following a literature search and thorough analysis of existing case difficulty
      assessment forms, the web-based tool was developed using an online survey builder
      (Qualtrics, Qualtrics Lab, UT, USA). Following feedback from a pilot study, it
      was refined and improved. A study was performed, using the updated version
      (EndoApp) on a cohort (n = 53) of dental professionals and dental students. The
      participants were e-mailed instructions detailing the assessment of five test
      cases using EndoApp, followed by completion of a structured feedback form.
      Analysis of the EndoApp responses was used to evaluate usage times, whereas the
      results of the feedback forms were used to assess user experience and relevance,
      other potential applications and comments on further improvement/s. RESULTS: The
      average usage time was 2 min 7 s; the average times needed for the last three
      (Cases 3-5) were significantly less than the preceding two (Cases 1 & 2) test
      cases. An overwhelming majority of participants expressed favourable views on
      user experience and relevance of the web-based case difficulty assessment tool.
      Only two participants (4%) were unlikely or very unlikely to use EndoApp again.
      The potential application of EndoApp as an 'educational tool' and for 'primary
      care triage' was deemed the most popular features and of greater importance than
      the secondary options of 'fee setting' and as a 'dento-legal justification tool'.
      CONCLUSIONS: Within the study limitations, owing to its ability to quantify the
      level of difficulty and provide guidance, EndoApp was considered user-friendly
      and helped facilitate endodontic case difficulty assessment. From the feedback,
      further improvements and the development of a Smartphone App version are in
      progress. CLINICAL RELEVANCE: EndoApp may facilitate treatment planning, improve
      treatment cost-effectiveness and reduce frequency of procedural errors by
      providing appropriate guidance on endodontic case management.

PMID- 29372445
TI  - Effectiveness of ultrasonically activated irrigation on root canal disinfection:
      a systematic review of in vitro studies.
AB  - OBJECTIVES: Reduction of microbial load from the root canal systems is a pre
      requisite for healing of lesions of endodontic origin. Such microbial reduction
      is influenced by the method of irrigant delivery and activation. The aim of this
      systematic review was to compare the effect of ultrasonically activated
      irrigation (UAI) with other irrigation techniques on the reduction of
      microorganisms during root canal disinfection. MATERIALS AND METHODS: The
      research question was created based on the PICO strategy. Two reviewers
      independently performed a comprehensive literature search in electronic
      databases. Following application of inclusion and exclusion criteria to the
      selected articles, a systematic data extraction sheet was constructed. The
      selected articles were assessed using methodological quality scoring protocol.
      The risk of bias in selected studies was critically assessed by two reviewers.
      RESULTS: A total of 15 articles were included for the systematic review. The
      included studies were heterogeneous in study design; hence, meta-analysis was not
      performed. The overall risk of bias for the selected studies was moderate.
      Overall, UAI showed superior reduction of microbial counts, resulting in better
      disinfection compared to other irrigation systems chosen for comparison in this
      review. CONCLUSION: The use of UAI can bring about superior microbial reduction
      within the root canal system compared to other irrigant activation techniques.
      CLINICAL RELEVANCE: Activation of irrigants with ultrasonic brings about
      significant bacterial reduction from the root canal systems compared to other
      methods of irrigant activation and conventional syringe irrigation. This might
      help in improving the outcome of root canal treatment.

PMID- 29372447
TI  - Lactobacillus rhamnosus intake can prevent the development of Candidiasis.
AB  - OBJECTIVE: This study aimed to investigate the influence of Lactobacillus
      rhamnosus intake on the development of candidiasis and cytokines release.
      MATERIAL AND METHODS: Candida suspensions were inoculated into the oral cavity of
      experimentally immunosuppressed mice for candidiasis induction. The animals were
      divided into experimental groups: candidiasis with no probiotic intake (F),
      candidiasis with probiotic intake during Candida inoculation (FP), and
      candidiasis with probiotic intake 14 days before inoculation with Candida (FPP);
      and control groups: (C), (CP), and (CPP) without inducing candidiasis with
      probiotic intake in the same manner as groups F, FP, and FPP, respectively. After
      these periods, samples were collected from the oral cavity for yeast counts and,
      after euthanasia, the tongues of the animals were removed for histological
      analysis. Sera samples were also collected for analysis of IL-1 beta, TNF-alpha,
      INF-gamma, IL-12, IL-4, and IL-10. RESULTS: FP group showed lower Candida counts
      in the oral cavity, and the presence of Candida was almost not detected in FPP
      group. In tissues, the counts of fungi were significantly lower in FPP group,
      followed by FP. Groups that consumed probiotics also had lower histological and
      inflammatory infiltrates compared to F. Cytokines analysis demonstrated low
      concentrations of TNF-alpha, IL-12, IL-4, and IL-10 in all the groups, and no
      statistical difference between them. The production of IL-6 could be better
      detected, and the experimental groups that consumed the probiotic showed
      significant lower levels of this cytokine. CONCLUSIONS: The results suggest that
      L. rhamnosus intake, especially preventively, may avoid or decrease the
      development of candidiasis in immunosuppressed mice. CLINICAL RELEVANCE: This
      work adds scientific evidences that probiotics intake can avoid the development
      of candidiasis.

PMID- 29372448
TI  - New Therapeutic Approaches for the Treatment of Hyperkalemia in Patients Treated
      with Renin-Angiotensin-Aldosterone System Inhibitors.
AB  - Hyperkalemia (serum potassium > 5.5 mEq/L) is a common clinical problem in
      patients with chronic kidney disease, hypertension, diabetes, and heart failure.
      It can result from increased K+ intake, impaired distribution between
      intracellular and extracellular spaces, and most frequently, decreased renal
      excretion. Patients at the highest risk of hyperkalemia are treated with renin
      angiotensin-aldosterone system inhibitors (RAASIs) as they improve cardiovascular
      and renal outcomes and are strongly recommended in clinical guidelines. However,
      RAASIs cause or increase the risk of hyperkalemia, a key limitation to fully
      titrate RAASIs in patients who are most likely to benefit from treatment. Until
      recently, drugs for the treatment of hyperkalemia presented limited efficacy
      and/or safety concerns and there was an unmet need of new drugs to control
      hyperkalemia while maintaining RAASI therapy. We provide an overview of the
      mechanisms involved in K+ homeostasis and the epidemiology and management of
      hyperkalemia as a complication in cardiovascular patients and, finally, analyze
      the efficacy and safety of two new polymer-based, non-systemic agents, patiromer
      calcium and sodium zirconium cyclosilicate (ZS-9), designed to increase fecal K+
      loss and to normalize elevated serum K+ levels and chronically maintain K+
      homeostasis in hyperkalemic patients treated with RAASIs.

PMID- 29372449
TI  - Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a
      Long-Term Follow-Up.
AB  - PURPOSE: Brugada syndrome is a hereditary disease linked with an increased risk
      of sudden death that may require an implantable cardioverter-defibrillator (ICD)
      in order to halt the arrhythmic events. The aim of this study was to identify
      possible triggers for appropriate ICD therapies in patients with Brugada
      syndrome, focusing on their past and current therapeutic profiles. METHODS:
      Thirty patients with high-risk Brugada syndrome, with ICD implanted at the
      Coimbra Hospital and University Center, were enrolled. Patients were questioned
      about their Brugada syndrome history, previous cardiac events, comorbidities,
      present and past medications, and physical activity. Patients were followed up
      during 5.8 +/- 5.3 years. The ICD was interrogated, and arrhythmic events and
      device therapies were recorded. The cohort who received appropriate ICD therapies
      was compared with the remaining patients to determine the potential link between
      clinical variables and potentially fatal arrhythmic events. RESULTS: More than
      half of the patients (53.3%) took at least one non-recommended drug, and 16.7%
      received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was
      a tendency for more appropriate ICD therapies in patients who took unsafe drugs
      (85.7 versus 45.5%, p = 0.062), and the mean time between unsafe drug intake and
      appropriate ICD therapies was 3.8 +/- 7.5 days. CONCLUSIONS: This study revealed
      that the medical community is still unaware of the pharmacological restrictions
      imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have
      a higher risk of ventricular arrhythmic events.

PMID- 29372450
TI  - Claims data-driven modeling of hospital time-to-readmission risk with latent
      heterogeneity.
AB  - Hospital readmission risk modeling is of great interest to both hospital
      administrators and health care policy makers, for reducing preventable
      readmission and advancing care service quality. To accommodate the needs of both
      stakeholders, a readmission risk model is preferable if it (i) exhibits superior
      prediction performance; (ii) identifies risk factors to help target the most at
      risk individuals; and (iii) constructs composite metrics to evaluate multiple
      hospitals, hospital networks, and geographic regions. Existing work mainly
      addressed the first two features and it is challenging to address the third one
      because available medical data are fragmented across hospitals. To simultaneously
      address all three features, this paper proposes readmission risk models with
      incorporation of latent heterogeneity, and takes advantage of administrative
      claims data, which is less fragmented and involves larger patient cohorts.
      Different levels of latent heterogeneity are considered to quantify the effects
      of unobserved factors, provide composite measures for performance evaluation at
      various aggregate levels, and compensate less informative claims data. To
      demonstrate the prediction performances of the proposed models, a real case study
      is considered on a state-wide heart failure patient cohort. A systematic
      comparison study is then carried out to evaluate the performances of 49 risk
      models and their variants.

PMID- 29372452
TI  - Hibiscus rosa sinensis mediate anxiolytic effect via modulation of ionotropic
      GABA-A receptors: possible mechanism of action.
AB  - The current study was designed with the aim to investigate anti-anxiety potential
      of Hibiscus rosa sinensis roots and its possible mechanism of action. For this
      purpose hole board test, elevated plus maze test and light/dark exploration test
      were employed. The ethanol extract of plant was administered orally at two
      different doses i.e. 100 and 500 mg/kg for consecutive 14 days. The results of
      present investigation indicate that plant extract significantly (p < 0.05)
      increased the number of head dips and rearings as compared to control on
      respective days of observation. The extract increased the time of permanence in
      open arms and the number of head dips in elevated plus maze. In light/dark test,
      our study indicate that Hibiscus rosa sinensis significantly (p < 0.05) increased
      the time spent in light compartment and number of entries as compared to control.
      In addition the anxiolytic effects of HRS at highest tested dose were blocked by
      flumazenil, a GABA-A receptor antagonist that indicate that Hibiscus rosa
      sinensis potentiated the GABAergic actions. The results propose that the ethanol
      extract of Hibiscus rosa sinensis has prospective anxiolytic effect in mice via
      inhibition of ionotropic GABA receptors, using different behavioral paradigms.

PMID- 29372453
TI  - HIV Partner Notification Values and Preferences Among Sex Workers, Fishermen, and
      Mainland Community Members in Rakai, Uganda: A Qualitative Study.
AB  - HIV partner notification involves contacting sexual partners of people who test
      HIV positive and referring them to HIV testing, treatment, and prevention
      services. To understand values and preferences of key and general populations in
      Rakai, Uganda, we conducted 6 focus group discussions and 63 in-depth interviews
      in high prevalence fishing communities and low prevalence mainland communities.
      Participants included fishermen and sex workers in fishing communities, male and
      female mainland community members, and healthcare providers. Questions explored
      three approaches: passive referral, provider referral, and contract referral.
      Qualitative data were coded and analyzed using a team-based matrix approach.
      Participants agreed that passive referral was most suitable for primary partners.
      Provider referral was acceptable in fishing communities for notifying multiple,
      casual partners. Healthcare providers voiced concerns about limited time,
      resources, and training for provider-assisted approaches. Options for partner
      notification may help people overcome barriers to HIV serostatus disclosure and
      help reach key populations.

PMID- 29372451
TI  - BiodentineTM material characteristics and clinical applications: a 3 year
      literature review and update.
AB  - INTRODUCTION: BiodentineTM has frequently been acknowledged in the literature as
      a promising material and serves as an important representative of tricalcium
      silicate based cements used in dentistry. AIM: To provide an update on the
      physical and biological properties of BiodentineTM and to compare these
      properties with those of other tricalcium silicate cements namely, different
      variants of mineral trioxide aggregate (MTA) such as ProRoot MTA, MTA Angelus,
      Micro Mega MTA (MM-MTA), Retro MTA, Ortho MTA, MTA Plus, GCMTA, MTA HP and
      calcium enriched mixture (CEM), Endosequence and BioaggregateTM. STUDY DESIGN: A
      comprehensive literature search for publications from November 20, 2013 to
      November 20, 2016 was performed by two independent reviewers on Medline (PubMed),
      Embase, Web of Science, CENTRAL (Cochrane), SIGLE, SciELO, Scopus, Lilacs and
      clinicaltrials.gov. Electronic and hand search was carried out to identify
      randomised control trials (RCTs), case control studies, case series, case
      reports, as well as in vitro and animal studies published in the English
      language. CONCLUSIONS: The enhanced physical and biologic properties of
      BiodentineTM could be attributed to the presence of finer particle size, use of
      zirconium oxide as radiopacifier, purity of tricalcium silicate, absence of
      dicalcium silicate, and the addition of calcium chloride and hydrosoluble
      polymer. Furthermore, as BiodentineTM overcomes the major drawbacks of MTA it has
      great potential to revolutionise the different treatment modalities in paediatric
      dentistry and endodontics especially after traumatic injuries. Nevertheless, high
      quality long-term clinical studies are required to facilitate definitive
      conclusions.

PMID- 29372455
TI  - Trends in AIDS Mortality, Retention in Opioid Agonist Therapy, and HIV RNA
      Suppression in HIV-Infected People Who Injected Drugs from 2000 to 2015.
AB  - AIDS is a major cause of preventable mortality in HIV-infected people who inject
      drugs (HIV-PWID). An observational study was conducted to examine trends in AIDS
      mortality and related factors among HIV-infected individuals who died between
      2000 and 2015 at an urban hospital. Overall HIV-mortality was 6.5% (413/6307)
      with no changes over time (p 0.76). AIDS mortality dropped in HIV-PWID (p 0.02)
      although it represented 26.4% at the end of study period. Age (per one-year
      increase) [odds ratio (OR) 0.95], third study period (2010-2015) (OR 0.54), HIV
      PWID on opioid agonist therapy (OAT) (OR 0.39), and HIV RNA suppression (OR 0.15)
      were associated with AIDS mortality. OAT was reported in 58.3% (161/276) and RNA
      suppression in 30.9% (85/276) of HIV-PWID. OAT non-retention was due to drop-outs
      [85.2% (98/115)] and rejection [14.8% (17/115)] in HIV-PWID. Therefore,
      additional strategies are required to improve OAT retention and HIV RNA
      suppression to continue reducing AIDS mortality.

PMID- 29372454
TI  - Avoidant Coping Mediates the Relationship Between Self-Efficacy for HIV
      Disclosure and Depression Symptoms Among Men Who Have Sex with Men Newly
      Diagnosed with HIV.
AB  - HIV diagnosis presents a critical opportunity to reduce secondary transmission,
      improve engagement in care, and enhance overall well-being. To develop relevant
      interventions, research is needed on the psychosocial experiences of newly
      diagnosed individuals. This study examined avoidant coping, self-efficacy for HIV
      disclosure decisions, and depression among 92 newly diagnosed men who have sex
      with men who reported recent sexual risk behavior. It was hypothesized that
      avoidant coping would mediate the relationship between self-efficacy and
      depression. Cross-sectional surveys were collected from participants 3 months
      after HIV diagnosis. To test for mediation, multiple linear regressions were
      conducted while controlling for HIV disclosure to sexual partners. Self-efficacy
      for HIV disclosure decisions showed a negative linear relationship to depression
      symptoms, and 99% of this relationship was mediated by avoidant coping. The index
      of mediation of self-efficacy on depression indicated a small-to-medium effect.
      Higher self-efficacy was related to less avoidant coping, and less avoidant
      coping was related to decreased depression symptoms, all else held constant.
      These findings highlight the role of avoidant coping in explaining the
      relationship between self-efficacy for HIV disclosure decisions and depression.

PMID- 29372456
TI  - Role of Gay Neighborhood Status and Other Neighborhood Factors in Racial/Ethnic
      Disparities in Retention in Care and Viral Load Suppression Among Men Who Have
      Sex with Men, Florida, 2015.
AB  - This study's objective was to examine the role of gay neighborhood residence and
      other neighborhood factors in racial/ethnic disparities in retention in HIV care
      and viral load suppression during 2015. Florida residents diagnosed 2000-2014
      with HIV infection and with transmission mode of men who have sex with men (MSM)
      were included in multi-level logistic regression models. Of 29,156 MSM, 29.4%
      were not retained and 34.2% were not virally suppressed. Non-Hispanic Blacks
      (NHB) had a higher likelihood of not being retained (adjusted prevalence ratio
      [aPR] 1.31, 95% confidence interval [CI] 1.24-1.38, p value < 0.0001) and not
      being virally suppressed (aPR 1.82, 95% CI 1.67-1.98, p value < 0.0001) compared
      with non-Hispanic Whites. Among NHBs, rural residence was protective for both
      outcomes. Although gay neighborhood residence was not associated with either
      outcome, the role of other neighborhood factors suggests that individual and
      neighborhood barriers to HIV care and treatment should be addressed among MSM.

PMID- 29372458
TI  - 1H, 15N, and 13C resonance assignments of the third domain from the S. aureus
      innate immune evasion protein Eap.
AB  - Staphylococcus aureus is a widespread and persistent pathogen of humans and
      livestock. The bacterium expresses a wide variety of virulence proteins, many of
      which serve to disrupt the host's innate immune system from recognizing and
      clearing bacteria with optimal efficiency. The extracellular adherence protein
      (Eap) is a multidomain protein that participates in various protein-protein
      interactions that inhibit the innate immune response, including both the
      complement system (Woehl et al in J Immunol 193:6161-6171, 2014) and Neutrophil
      Serine Proteases (NSPs) (Stapels et al in Proc Natl Acad Sci USA 111:13187-13192,
      2014). The third domain of Eap, Eap3, is an ~ 11 kDa protein that was recently
      shown to bind complement component C4b (Woehl et al in Protein Sci 26:1595-1608,
      2017) and therefore play an essential role in inhibiting the classical and lectin
      pathways of complement (Woehl et al in J Immunol 193:6161-6171, 2014). Since
      structural characterization of Eap3 is still incomplete, we acquired a series of
      2D and 3D NMR spectra of Eap3 in solution. Here we report the backbone and side
      chain 1H, 15N, and 13C resonance assignments of Eap3 and its predicted secondary
      structure via the TALOS-N server. The assignment data have been deposited in the
      BMRB data bank under accession number 27087.

PMID- 29372457
TI  - The calmodulin-like protein, CML39, is involved in regulating seed development,
      germination, and fruit development in Arabidopsis.
AB  - KEY MESSAGE: We show that the calcium sensor, CML39, is important in various
      developmental processes from seeds to mature plants. This study bridges previous
      work on CML39 as a stress-induced gene and highlights the importance of calcium
      signalling in plant development. In addition to the evolutionarily-conserved Ca2+
      sensor, calmodulin (CaM), plants possess a large family of CaM-related proteins
      (CMLs). Using a cml39 loss-of-function mutant, we investigated the roles of CML39
      in Arabidopsis and discovered a range of phenotypes across developmental stages
      and in different tissues. In mature plants, loss of CML39 results in shorter
      siliques, reduced seed number per silique, and reduced number of ovules per
      pistil. We also observed changes in seed development, germination, and seed coat
      properties in cml39 mutants in comparison to wild-type plants. Using radicle
      emergence as a measure of germination, cml39 mutants showed more rapid
      germination than wild-type plants. In marked contrast to wild-type seeds, the
      germination of developing, immature cml39 seeds was not sensitive to cold
      stratification. In addition, germination of cml39 seeds was less sensitive than
      wild-type to inhibition by ABA or by treatments that impaired gibberellic acid
      biosynthesis. Tetrazolium red staining indicated that the seed-coat permeability
      of cml39 seeds is greater than that of wild-type seeds. RNA sequencing analysis
      of cml39 seedlings suggests that changes in chromatin modification may underlie
      some of the phenotypes associated with cml39 mutants, consistent with previous
      reports that orthologs of CML39 participate in gene silencing. Aberrant ectopic
      expression of transcripts for seed storage proteins in 7-day old cml39 seedlings
      was observed, suggesting mis-regulation of early developmental programs.
      Collectively, our data support a model where CML39 serves as an important Ca2+
      sensor during ovule and seed development, as well as during germination and
      seedling establishment.

PMID- 29372459
TI  - 1H, 13C, 15N resonance assignment of human YAP 50-171 fragment.
AB  - Yes associated protein (YAP) is an intrinsically disordered protein that plays a
      major role in the Hippo pathway, regulating organ size, cell proliferation,
      apoptosis, and is associated with cancer development. Therefore, the binding
      between YAP and TEAD is an interesting target for cancer therapy. The TEAD
      binding domain of YAP was mapped to protein residues 50-171. To obtain further
      structural insights into this 12 kDa segment of YAP, we report a backbone and a
      partial sidechain assignment of recombinant YAP 50-171.

PMID- 29372460
TI  - Preliminary opinion on assessment categories of stomach ultrasound report and
      data system (Su-RADS).
AB  - OBJECTIVE: Transabdominal ultrasound after oral administration of an echoic
      cellulose-based gastric ultrasound contrast agent (TUS-OCCA) has recently been
      suggested as a valuable mass-screening tool for gastric cancer. The aim of this
      study was to propose a producible stomach ultrasound reporting and data system
      (Su-RADS) using TUS-OCCA for gastric cancer screening. PATIENTS: The study
      includes information of 2738 patients who underwent both gastroscopy and TUS-OCCA
      examinations recorded in software system. Gastroscopy examination with
      pathological diagnosis was considered as gold standard. Various gastric lesions
      were classified into category 1-5 based on gastric wall thicknesses of them
      (especially the mucosa layer). RESULTS: The total malignant ratios of patients
      enrolled in this study were 17.1% (469/2738). The malignant ratios for category 1
      5 were, respectively, 1.1, 1.7, 12.2, 34.2 and 78.1%. Category 2 indicated mild
      thickening of gastric wall at low risk for malignancy (1.7%); category 3
      indicated moderate thickening at moderate risk for malignancy (12.2%); category 4
      indicated severe thickening at high risk for malignancy (34.2%); category 5
      indicated extremely severe thickening at extremely high risk for malignancy
      (78.1%). If category 2 was identified as cut-off point distinguishing between
      benign and malignant, the sensitivity and specificity by Su-RADS are 95.1 and
      78.6%, respectively. CONCLUSION: The Su-RADS system could inform the physicians
      about key findings, indicating the risk for malignancy and necessity of
      additional gastroscopy examination. Prospectively randomly controlled study
      design with larger clinical trial is needed for further investigations.

PMID- 29372462
TI  - Bias in matched case-control studies: DAGs are not enough.

PMID- 29372461
TI  - Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with
      advanced gastric cancer: the Korean Cancer Study Group ST14-11.
AB  - BACKGROUND: Doublet chemotherapy of platinum and 5-fluorouracil is a standard
      first-line treatment for patients with unresectable gastric cancer. Although the
      addition of taxane or irinotecan to this regimen has yielded promising efficacy,
      its use has been limited due to severe toxicities. To overcome this limitation,
      we evaluated the efficacy and safety of the combination of irinotecan,
      oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer. METHODS:
      Chemotherapy-naive patients with pathologically proven advanced gastric
      adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and
      oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80
      mg/m2/day) was administered orally on days 1-7 of every 2-week cycle. RESULTS:
      Forty-four patients (median age 57 years) were enrolled and all but one patient
      had a good performance status (ECOG 0 or 1). A total of 529 cycles were
      administered, with a median of 9.5 (range 1-31) cycles per patient. The overall
      response rate was 61.4% (95% confidence interval [CI] 46.6-74.3). The median
      progression-free survival and overall survival were 10.8 months (95% CI 7.6-14.0)
      and 15.4 months (95% CI 12.6-18.2), respectively. Major toxicities included grade
      3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and
      diarrhea (9.1%). CONCLUSION: These data suggest that the OIS regimen is effective
      and relatively well tolerated in patients with advanced gastric cancer. Given
      that all the patients treated, but one, had a good performance status, these
      results must be confirmed in a patient population more representative of regular
      clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT02527785.

PMID- 29372463
TI  - Dietary non enzymatic antioxidant capacity and the risk of myocardial infarction
      in the Swedish women's lifestyle and health cohort.
AB  - Foods rich in antioxidants have been associated with a reduced risk of myocardial
      infarction. However, findings from randomized clinical trials on the role of
      antioxidant supplementation remain controversial. It has been suggested that
      antioxidants interact with each other to promote cardiovascular health. We
      therefore investigated the association between dietary Non Enzymatic Antioxidant
      Capacity (NEAC), measuring the total antioxidant potential of the whole diet, and
      the risk of myocardial infarction. We followed 45,882 women aged 30-49 years and
      free from cardiovascular diseases through record linkages from 1991 until 2012.
      Dietary NEAC was assessed by a validated food frequency questionnaire collected
      at baseline. Total dietary NEAC was categorized into quintiles and multivariable
      Cox proportional hazard regression models were fitted to estimate hazard ratios
      (HR) with 95% confidence intervals (CI). During a mean follow-up time of 20.3
      years we detected 657 incident cases of myocardial infarction. After adjusting
      for potential confounders, we found a significant 28% lower risk of myocardial
      infarction among women in the fourth (HR: 0.72; 95% CI 0.55-0.95) and a 40% lower
      risk among women in the fifth quintile (HR: 0.60, 95% CI 0.45-0.81) of dietary
      NEAC compared to women in the first quintile, with a significant trend (p-value <
      0.001). Higher dietary NEAC is associated with a lower risk of myocardial
      infarction in young to middle-aged women. These findings support the hypothesis
      that dietary antioxidants protect from myocardial infarction and that this effect
      might be exerted through interactions between antioxidants.

PMID- 29372465
TI  - Melilotus indicus extract induces apoptosis in hepatocellular carcinoma cells via
      a mechanism involving mitochondria-mediated pathways.
AB  - Melilotus indicus, is a traditional medicine used as analgesic and emollient.
      Although Melilotus indicus extract (MIE) has recently been shown to suppress
      growth of several tumor cell lines, information regarding its antitumor mechanism
      is completely unknown. Here, we report the mechanism underlying the effects of
      MIE on human hepatocellular carcinoma cells, specifically HepG2, and SNU-182
      cells. Methanolic MIE impaired the proliferation, and induced cell death in both
      HepG2 and SNU-182 cells but not in normal hepatic L-02 cells. Mechanistically,
      flow cytometric analysis revealed that MIE induces apoptosis in HepG2, and SNU
      182 cells. However, MIE-induced apoptosis were not affected by a pan caspase
      inhibitor z-VAD-fmk as well as MIE did not stimulate caspase activation.
      Furthermore we found that MIE-induced apoptosis could be attributed to a
      mechanism involving mitochondria-mediated pathways evidenced by decrease in the
      mitochondrial membrane potential (DeltaPsim), increase in the Bax/Bcl-2 ratio,
      and translocation of apoptosis inducing factor (AIF) from the mitochondria to the
      nucleus. Suppression in AIF expression by siRNA reduced MIE-induced apoptosis
      which suggested the dependency of MIE on AIF to induce apoptosis in
      hepatocellular carcinoma cells. To the best of our knowledge this is the first
      report elucidating the anticancer mechanism of MIE. Our findings suggested that
      MIE might be a good extract for developing anticancer drugs for human
      hepatocellular carcinoma treatment.

PMID- 29372466
TI  - Co-cultured the MSCs and cardiomyocytes can promote the growth of cardiomyocytes.
AB  - Recently, the incidence of myocardial infarction has been increasing annually.
      Now cell therapy is a major new strategy in the treatment of this public health
      challenge. Most recently, evidences showed that MSCs can reduce the area of
      infarction and improve the heart function. In our study we found that MSCs could
      promote cardiomyocytes proliferation, inhibit the apoptosis of cardiomyocytes and
      promote cardiomyocytes autophagy function. These functions could be a therapeutic
      effect on myocardial infarction. At the same time, we first revealed that MSCs
      may achieve these functions by the activation of VEGF signaling pathways.

PMID- 29372464
TI  - The Potential of Stem Cells in Treatment of Traumatic Brain Injury.
AB  - PURPOSE OF REVIEW: Traumatic brain injury (TBI) is a global public health
      concern, with limited treatment options available. Despite improving survival
      rate after TBI, treatment is lacking for brain functional recovery and structural
      repair in clinic. Recent studies have suggested that the mature brain harbors
      neural stem cells which have regenerative capacity following brain insults. Much
      progress has been made in preclinical TBI model studies in understanding the
      behaviors, functions, and regulatory mechanisms of neural stem cells in the
      injured brain. Different strategies targeting these cell population have been
      assessed in TBI models. In parallel, cell transplantation strategy using a wide
      range of stem cells has been explored for TBI treatment in pre-clinical studies
      and some in clinical trials. This review summarized strategies which have been
      explored to enhance endogenous neural stem cell-mediated regeneration and recent
      development in cell transplantation studies for post-TBI brain repair. RECENT
      FINDINGS: Thus far, neural regeneration through neural stem cells either by
      modulating endogenous neural stem cells or by stem cell transplantation has
      attracted much attention. It is highly speculated that targeting neural stem
      cells could be a potential strategy to repair and regenerate the injured brain.
      Neuroprotection and neuroregeneration are major aspects for TBI therapeutic
      development. With technique advancement, it is hoped that stem cell-based therapy
      targeting neuroregeneration will be able to translate to clinic in not so far
      future.

PMID- 29372467
TI  - The formation of intestinal organoids in a hanging drop culture.
AB  - Recently organoids have become widely used in vitro models of many tissue and
      organs. These type of structures, originated from embryonic or adult mammalian
      intestines, are called "mini guts". They organize spontaneously when intestinal
      crypts or stem cells are embedded in the extracellular matrix proteins
      preparation scaffold (Matrigel). This approach has some disadvantages, as
      Matrigel is undefined (the concentrations of growth factors and other
      biologically active components in it may vary from batch to batch), difficult to
      handle and expensive. Here we show that the organoids derived from chicken embryo
      intestine are formed in a hanging drop without embedding, providing an attractive
      alternative for currently used protocols. Using this technique we obtained
      compact structures composed of contiguous organoids, which were generally similar
      to chicken organoids cultured in Matrigel in terms of morphology and expression
      of intestinal epithelial markers. Due to the simplicity, high reproducibility and
      throughput capacity of hanging drop technique our model may be applied in various
      studies concerning the gut biology.

PMID- 29372468
TI  - Characterization of female germline stem cells from adult mouse ovaries and the
      role of rapamycin on them.
AB  - Germline stem cells (GSCs) play an indispensable role in establishing the
      fertility of an organism. The isolation and culture of adult female GSCs (FGSCs)
      have provided a robust foundation to study the development of female germ cells
      in rodents. However, many problems still need to be identified, such as the
      origin and location of FGSCs and the specific markers for screening. In this
      study, we acquired FGSCs that stably expressed Oct4 from Oct4 promoter-GFP
      transgenic mouse ovarian surface epithelium and cortical layer, and identified
      the cells possessing the representative features including the expression of GSCs
      marker genes and the potentiality of differentiation into all three germ layers
      in vitro. Moreover, rapamycin was confirmed to promote proliferation of mouse
      FGSCs and inhibit the differentiation capability in vivo. In addition to the
      reported disinfection function, rapamycin inhibited the activation of primordial
      follicles, as the inhibitor of mechanistic target of rapamycin pathway. These
      results will contribute to the study on folliculogenesis or oogenesis mechanism
      and have important implications on developing new technology and therapeutic
      approach in medicine for premature ovarian failure, infertility and even ovary
      remodelling in future.

PMID- 29372469
TI  - Single-breath-hold abdominal [Formula: see text]  mapping using 3D Cartesian Look
      Locker with spatiotemporal sparsity constraints.
AB  - OBJECTIVE: Our aim was to develop and validate a 3D Cartesian Look-Locker
      [Formula: see text] mapping technique that achieves high accuracy and whole-liver
      coverage within a single breath-hold. MATERIALS AND METHODS: The proposed method
      combines sparse Cartesian sampling based on a spatiotemporally incoherent Poisson
      pattern and k-space segmentation, dedicated for high-temporal-resolution imaging.
      This combination allows capturing tissue with short relaxation times with
      volumetric coverage. A joint reconstruction of the 3D + inversion time (TI) data
      via compressed sensing exploits the spatiotemporal sparsity and ensures
      consistent quality for the subsequent multistep [Formula: see text] mapping. Data
      from the National Institute of Standards and Technology (NIST) phantom and 11
      volunteers, along with reference 2D Look-Locker acquisitions, are used for
      validation. 2D and 3D methods are compared based on [Formula: see text] values in
      different abdominal tissues at 1.5 and 3 T. RESULTS: [Formula: see text] maps
      obtained from the proposed 3D method compare favorably with those from the 2D
      reference and additionally allow for reformatting or volumetric analysis.
      Excellent agreement is shown in phantom [bias[Formula: see text] < 2%,
      bias[Formula: see text] < 5% for (120; 2000) ms] and volunteer data (3D and 2D
      deviation < 4% for liver, muscle, and spleen) for clinically acceptable scan (20
      s) and reconstruction times (< 4 min). CONCLUSION: Whole-liver [Formula: see
      text] mapping with high accuracy and precision is feasible in one breath-hold
      using spatiotemporally incoherent, sparse 3D Cartesian sampling.

PMID- 29372470
TI  - Uric acid-lowering and renoprotective effects of topiroxostat, a selective
      xanthine oxidoreductase inhibitor, in patients with diabetic nephropathy and
      hyperuricemia: a randomized, double-blind, placebo-controlled, parallel-group
      study (UPWARD study).
AB  - BACKGROUND: Hyperuricemia is supposed to be an independent risk factor for kidney
      dysfunction in diabetic patients. We attempted to examine the uric acid-lowering
      effect and the renoprotective effect of topiroxostat, a selective xanthine
      oxidoreductase inhibitor, in patients with diabetic nephropathy and hyperuricemia
      in this pilot study. METHODS: The study design was randomized, double-blind,
      placebo-controlled, parallel-group study. A total of 65 patients with
      hyperuricemia and diabetic nephropathy with microalbuminuria were enrolled and
      assigned to either the topiroxostat group or the placebo group. Topiroxostat
      (stepwise dosing from 40 to 160 mg/day) or matching placebo was administered BID
      for 28 weeks. The primary endpoint was a change in the urinary albumin-to
      creatinine ratio in the first-morning-void urine sample. Secondary endpoints were
      changes in the estimated glomerular filtration rate and the serum uric acid
      level. RESULTS: At 28 weeks, there was no significant difference in the percent
      change from baseline in the urinary albumin-to-creatinine ratio between the two
      groups (topiroxostat: 0 vs. placebo: 17%, p = 0.3206), but the changes in the
      estimated glomerular filtration rate (- 0.2 vs. - 4.0 mL/min/1.73 m2, p = 0.0303)
      and the serum uric acid level (- 2.94 vs. - 0.20 mg/dL, p < 0.0001) were
      significantly different between the topiroxostat and placebo groups. Gouty
      arthritis occurred in 1 patient in the placebo group and no patients in the
      topiroxostat group. CONCLUSION: These findings support that diabetic nephropathy
      combined with hyperuricemia may be associated with kidney dysfunctions.
      Topiroxostat provides strict control of the serum uric acid level preventing
      decline of eGFR in these patients.

PMID- 29372471
TI  - Validation of estimated glomerular filtration rate equations for Japanese
      children.
AB  - BACKGROUND: The gold standard for evaluation of kidney function is renal inulin
      clearance (Cin). However, the methodology for Cin is complicated and difficult,
      especially for younger children and/or patients with bladder dysfunction.
      Therefore, we developed a simple and easier method for obtaining the estimated
      glomerular filtration rate (eGFR) using equations and values for several
      biomarkers, i.e., serum creatinine (Cr), serum cystatin C (cystC), serum beta-2
      microglobulin (beta2MG), and creatinine clearance (Ccr). The purpose of the
      present study was to validate these equations with a new data set. METHODS: To
      validate each equation, we used data of 140 patients with CKD with clinical need
      for Cin, using the measured GFR (mGFR). We compared the results for each eGFR
      equation with the mGFR using mean error (ME), root mean square error (RMSE), P30,
      and Bland-Altman analysis. RESULTS: The ME of Cr, cystC, beta2MG, and Ccr based
      on eGFR was 15.8 +/- 13.0, 17.2 +/- 16.5, 15.4 +/- 14.3, and 10.6 +/- 13.0
      ml/min/1.73 m2, respectively. The RMSE was 29.5, 23.8, 20.9, and 16.7,
      respectively. The P30 was 79.4, 71.1, 69.5, and 92.9%, respectively. The Bland
      Altman bias analysis showed values of 4.0 +/- 18.6, 5.3 +/- 16.8, 12.7 +/- 17.0,
      and 2.5 +/- 17.2 ml/min/1.73 m2, respectively, for these parameters. CONCLUSION:
      The bias of each eGFR equation was not large. Therefore, each eGFR equation could
      be used.

PMID- 29372472
TI  - Detection of copy number variations by pair analysis using next-generation
      sequencing data in inherited kidney diseases.
AB  - BACKGROUND: Comprehensive genetic approaches for diagnosing inherited kidney
      diseases using next-generation sequencing (NGS) have recently been established.
      However, even with these approaches, we are still failing to detect gene defects
      in some patients who appear to suffer from genetic diseases. One of the reasons
      for this is the difficulty of detecting copy number variations (CNVs) using our
      current approaches. For such cases, we can apply methods of array-based
      comparative genomic hybridization (aCGH) or multiplex ligation and probe
      amplification (MLPA); however, these are expensive and laborious and also often
      fail to identify CNVs. Here, we report seven cases with CNVs in various inherited
      kidney diseases screened by NGS pair analysis. METHODS: Targeted sequencing
      analysis for causative genes was conducted for cases with suspected inherited
      kidney diseases, for some of which a definitive genetic diagnosis had not been
      achieved. We conducted pair analysis using NGS data for those cases. When CNVs
      were detected by pair analysis, they were confirmed by aCGH and/or MLPA. RESULTS:
      In seven cases, CNVs in various causative genes of inherited kidney diseases were
      detected by pair analysis. With aCGH and/or MLPA, pathogenic CNV variants were
      confirmed: COL4A5 or HNF1B in two cases each, and EYA1, CLCNKB, or PAX2 in one
      each. CONCLUSION: We presented seven cases with CNVs in various genes that were
      screened by pair analysis. The NGS-based CNV detection method is useful for
      comprehensive screening of CNVs, and our results revealed that, for a certain
      proportion of cases, CNV analysis is necessary for accurate genetic diagnosis.

PMID- 29372473
TI  - The Sendai declaration for the eradication of kidney disease.

PMID- 29372474
TI  - Optimal conditions and the advantages of using laser microdissection and liquid
      chromatography tandem mass spectrometry for diagnosing renal amyloidosis.
AB  - BACKGROUND: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has
      recently been utilized to accurately detect the amyloid proteins of renal
      amyloidosis. The present study investigated the optimal procedures for analyzing
      samples by LCMS/MS, and the advantage of using this technique to diagnosis renal
      amyloidosis. METHODS: To detect amyloid proteins, laser microdissected glomeruli
      from AL (n = 13) or AA (n = 10) renal amyloidosis patients were digested and
      analyzed by LCMS/MS. To determine the best procedures for analyzing samples by
      LCMS/MS, we examined the suitability of tissue samples, frozen or formalin-fixed
      paraffin-embedded (FFPE), the number of dissected glomeruli required for analysis
      (2, 10, or 50 glomeruli), and the amount of trypsin with or without
      dithiothreitol (DTT). We additionally compared the detection of amyloid proteins
      between immunostaining and LCMS/MS. RESULTS: Examining 10 dissected glomeruli
      from FFPE sections digested with trypsin 3 uL (0.1 mg/mL) without DDT made it
      possible to detect amyloid protein in all 10 AA and in 10 out of 12 AL
      amyloidosis cases. All AA amyloidosis cases were diagnosed using
      immunohistochemistry for amyloid A. With immunostaining, however, there were
      several inconclusive immunoglobulin and/or their light chain staining noted in
      the AA or AL amyloidosis cases. Even so, LCMS/MS was able to accurately detect
      amyloid protein in renal amyloidosis. CONCLUSION: The use of 10 laser
      microdissected glomeruli (170,000-220,000 um2) with amyloid deposition from FFPE
      sections digested with trypsin 3 uL (0.1 mg/mL) allowed the accurate detection of
      amyloid protein in AA and AL amyloidosis.

PMID- 29372475
TI  - Acid Secretion and Its Relationship to Esophageal Reflux Symptom in Patients with
      Subtotal Gastrectomy.
AB  - BACKGROUND: Esophageal reflux symptom has been reported as common in patients
      with subtotal gastrectomy. Management of postoperative esophageal reflux symptom
      is not satisfactory. The aim of this study is to investigate prevalence of
      esophageal reflux symptom after subtotal gastrectomy and assess factors affecting
      esophageal reflux symptom in subtotal gastrectomy patients. METHODS: We
      prospectively enrolled 100 consecutive patients with subtotal gastrectomy who
      were regularly followed up by endoscopic examination. Acid secretory capacity was
      assessed by measuring messenger RNA (mRNA) expression of H+/K+-adenosine
      triphosphatase (ATPase) via real-time polymerase chain reaction (PCR) in biopsy
      specimens. RESULTS: In total, 47 % of patients had typical esophageal reflux
      symptom, where heartburn or regurgitation was experienced at least weekly. Age,
      sex, body mass index, and type of reconstruction did not differ between
      esophageal reflux and non-esophageal-reflux groups. The esophageal reflux group
      had longer duration from time of operation until study (median 5.0 versus 3.6
      years; P = 0.017). Hill grade for gastroesophageal (GE) flap valve was higher in
      the esophageal reflux group than in the non-esophageal-reflux group (P = 0.027).
      H+/K+-ATPase mRNA expression was higher in the esophageal reflux group than in
      the non-esophageal-reflux group [3967.6 (+/- 7583.7) versus 896.2 (+/- 1456.0); P
      = 0.006]. Multivariate analysis revealed that postoperative duration, H+/K+
      ATPase mRNA expression level, and GE flap valve disruption were significantly
      associated with esophageal reflux symptom development. CONCLUSIONS: Esophageal
      reflux symptom is common in patients after subtotal gastrectomy, possibly because
      of anti-reflux-barrier impairment and preservation of acid secretory capacity
      following surgery. Optimal acid suppression may be helpful in managing
      postoperative esophageal reflux symptom.

PMID- 29372476
TI  - Identification of Candidate Biomarkers Associated with Response to Vedolizumab in
      Inflammatory Bowel Disease.
AB  - BACKGROUND/AIMS: Vedolizumab is an anti-alpha4beta7 monoclonal antibody approved
      for the treatment of inflammatory bowel disease (IBD). This exploratory study
      aimed to identify biomarkers associated with vedolizumab response. METHODS:
      Twenty-six IBD patients (15 with Crohn's, 11 with ulcerative or indeterminate
      colitis) initiating vedolizumab at a single center between 2014 and 2016
      underwent sampling of serum and peripheral blood mononuclear cells (PBMCs) before
      and during vedolizumab therapy. Response was defined as steroid-free improvement
      in endoscopic score or Harvey-Bradshaw index/simple clinical colitis activity
      index (reduction greater than 3 or total less than 3). PBMCs were evaluated for
      immunophenotype and expression of alpha4beta7 integrin on lymphocytes before and
      during vedolizumab therapy. Serum vedolizumab levels and alpha4beta7 saturation
      were measured serially after induction. RESULTS: Fourteen out of 26 (54%)
      patients treated with vedolizumab responded to therapy. Pretreatment alpha4beta7
      expression was higher in responders on multiple subsets of T, B, and NK cells,
      with terminal effector memory (p = .0009 for CD4 and .0043 for CD8) and NK cells
      (p = .0047) best discriminating between responders and nonresponders. During
      therapy, log10 serum vedolizumab levels at trough were higher in responders than
      nonresponders (p = .0007). Conversely, the percentage of effector memory T cells
      with free alpha4beta7 at trough was lower in responders than nonresponders (p <
      .0001). However, loss of alpha4beta7 saturation with vedolizumab was more
      sensitive to low serum vedolizumab in nonresponders. CONCLUSIONS: Pretreatment
      alpha4beta7 expression and alpha4beta7 receptor saturation during maintenance
      therapy were identified as candidate biomarkers for vedolizumab response.

PMID- 29372477
TI  - Loss of Response to Anti-Tumor Necrosis Factor Alpha Therapy in Crohn's Disease
      Is Not Associated with Emergence of Novel Inflammatory Pathways.
AB  - BACKGROUND: While monoclonal antibodies against tumor necrosis factor-alpha
      (TNFalpha) are effective in treating Crohn's disease (CD), approximately one
      third of patients lose response. The mechanisms underlying this loss of response
      remain elusive. AIM: We sought to determine if novel biological pathways,
      including TNFalpha-independent inflammatory pathways, emerge in those with loss
      of response to anti-TNFalpha. METHODS: Using RNA microarray technology in 28
      patients with CD, we examined the colonic gene expression differences between
      those with active inflammation in the setting of loss of response to TNFalpha
      antagonist therapy ("loss of responders") compared to anti-TNFalpha naive
      patients with active inflammation and those on anti-TNF therapy in disease
      remission. Pathway enrichment analyses were performed. RESULTS: We found that
      colonic expression of chemokines known to drive inflammation (CXCL20, CXCL9, and
      CXCL10) was elevated in those with loss of response compared to those in
      remission. Expression of genes critical to modulating oxidative stress burden
      (DUOX2, DUOXA2, and NOS2) was also elevated. Additionally, MMP3, MMP1, and MMP12
      were elevated in those with continued inflammation. Gene enrichment analysis
      revealed that loss of responders exhibited dysregulation in the cysteine and
      methionine metabolism pathway, suggesting alteration in oxidative stress burden.
      There were no differences in genes or pathways between loss of responders and
      those who were TNFalpha-naive. However, loss of response occurred despite the
      ability of anti-TNFalpha therapy to normalize APO gene expression. CONCLUSION:
      Our analyses suggest that loss of response to anti-TNFalpha is not driven by the
      emergence of pathways that bypass the action or induce resistance to anti
      TNFalpha therapy.

PMID- 29372478
TI  - Arteriosclerosis Is a Major Predictor of Small Bowel Vascular Lesions.
AB  - BACKGROUND: Most studies have focused on evaluating the association between the
      presence of small bowel vascular lesions (SBVLs) and patients' comorbidities.
      AIMS: We sought to uncover a more fundamental indicator that may predict the
      presence of SBVLs by considering atherosclerosis qualitatively and
      quantitatively. METHODS: We enrolled 79 consecutive patients with obscure
      gastrointestinal bleeding who had undergone computed tomography (CT) and capsule
      endoscopy or double-balloon endoscopy from January 2015 to June 2017. The SBVL
      frequency, type, and location, and the relationship between the presence of SBVLs
      and the patients' clinical characteristics were evaluated. Arterial wall
      calcification was assessed on unenhanced CT images, and a modified Agatston
      scoring system was used to determine the abdominal aorta calcium scores. RESULTS:
      Of the 27 (34%) patients with SBVLs, 15 (19%) had type 1a, 12 (15%) had type 1b,
      and 2 (3%) had type 2a SBVLs. Most of the lesions were located in the jejunum.
      Cardiovascular disease (P = .017), chronic kidney disease (P = .025), and
      arteriosclerosis (P = .0036) were associated with the presence of SBVLs.
      Subsequent multivariate analysis revealed that arteriosclerosis (odds ratio [OR]
      7.29; 95% confidence interval [CI] 1.13-143.9) and superior mesenteric artery
      calcification (OR 16.3; 95% CI 3.64-118.6) were independent predictors of the
      presence of SBVLs. The modified Agatston score was significantly higher in SBVL
      cases than in non-SBVL cases (6384 vs. 2666, P = .0023). CONCLUSIONS:
      Arteriosclerosis, especially increased superior mesenteric artery calcification,
      is associated with an increased likelihood of SBVLs.

PMID- 29372479
TI  - Neuronal Nitric Oxide Synthase Is a Novel Biomarker for the Interstitial Cells of
      Cajal in Stress-Induced Diarrhea-Dominant Irritable Bowel Syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal
      disorder involving changes in normal bowel movements. The pathophysiology of IBS
      is not clearly understood owing to the lack of identifiable pathological
      abnormalities and reliable biomarkers. AIM: The aim of this study was to discover
      the novel and reliable biomarker for IBS. METHOD: In this study, neonatal
      maternal separation (NMS) stress model was used for the IBS mouse model. Further
      assessment was conducted with whole gastrointestinal transit test, quantitative
      RT-PCR, histological examination, and western blot. RESULTS: Male pups developed
      symptoms similar to those of human IBS with diarrhea (IBS-D), such as low-grade
      inflammation, stool irregularity, and increased bowel motility. NMS stress
      influenced to the interstitial cells of Cajal (ICC) and induced altered bowel
      motility, resulting in IBS-D-like symptoms. In addition, we found neuronal nitric
      oxide synthase (nNOS) to be a novel biomarker for ICC under NMS stress. nNOS
      expression was only observed in the ICC of the submucosal plexus of IBS-D mice,
      and the inhibition of nNOS changed the phenotype from IBS-D to IBS with
      constipation. CONCLUSION: Our study demonstrates that early-life stress can
      influence to ICC and modulate bowel activity and that nNOS might be used as a
      biomarker for ICC stimulation in IBS.

PMID- 29372480
TI  - Adalimumab for Induction of Histological Remission in Moderately to Severely
      Active Ulcerative Colitis.
AB  - BACKGROUND: Histological remission represents a target distinct from endoscopic
      healing in ulcerative colitis (UC) and seems a better predictor of clinical
      outcomes. AIMS: The aim of this study was to assess the ability of adalimumab to
      achieve histological remission in UC patients. METHODS: Single-center,
      retrospective, open-label study of patients treated with adalimumab. Eligible
      patients were anti-TNF naive adults with moderately to severely active UC. The
      Mayo score including endoscopy was performed at baseline and weeks 8 and 52.
      Histological activity was scored using the Geboes Index. The primary endpoint was
      histological remission, defined as a Geboes grade <= 3.0, at week 52. RESULTS: We
      included 34 patients. At week 8, 6 of 34 patients (17.6%) achieved histological
      remission. At week 52, 9 patients (26.5%, intention to treat; 31%, per protocol)
      had histological remission. Patients had a significant and progressive reduction
      in the most severe subgrades of Geboes Index from baseline at weeks 8 and 52. At
      weeks 8 and 52, 50 and 61.8% of patients achieved mucosal healing (Mayo
      endoscopic subscore 0-1). All patients who achieved histological remission also
      had mucosal healing. At week 8, 85.3 and 20.6% of patients achieved clinical
      response (decrease in Mayo score <= 3 points) or remission (Mayo score <= 2),
      respectively. At week 52, the corresponding values were 67.6 and 52.9%,
      respectively. At week 52, agreement between histological remission and mucosal
      healing was fair (kappa 0.293). Agreement between histological remission and Mayo
      endoscopic subscore 0 was good (kappa 0.71). CONCLUSIONS: Adalimumab was able to
      achieve histological remission in anti-TNF naive patients with moderately to
      severely active UC.

PMID- 29372482
TI  - Thyroid disorders in alemtuzumab-treated multiple sclerosis patients: a Belgian
      consensus on diagnosis and management.
AB  - This paper deals with thyroid disease that can occur after treatment with
      alemtuzumab (humanized monoclonal anti-CD52) for relapsing-remitting multiple
      sclerosis (MS). The 5-year incidence of thyroid adverse events in phase 3
      clinical trials is up to 40.7%. In most cases, the thyroid dysfunction is mild
      and easily manageable and only few serious thyroid adverse events have been
      reported. The need for patient education on the risk of thyroid dysfunction, as
      well as regular clinical and biochemical thyroid function screening is well
      described. However, practical clinical guidance in case of abnormal thyroid
      related findings prior to or after alemtuzumab treatment is currently lacking.
      Therefore, a Belgian taskforce consisting of MS and thyroid experts was created
      in 2016, with the objective of issuing a clinical thyroid management algorithm
      based on available scientific evidence and personal experience with regard to
      alemtuzumab treatment-related thyroid adverse events.

PMID- 29372483
TI  - Next-Generation Theranostic Agents Based on Polyelectrolyte Microcapsules Encoded
      with Semiconductor Nanocrystals: Development and Functional Characterization.
AB  - Fabrication of polyelectrolyte microcapsules and their use as carriers of drugs,
      fluorescent labels, and metal nanoparticles is a promising approach to designing
      theranostic agents. Semiconductor quantum dots (QDs) are characterized by
      extremely high brightness and photostability that make them attractive
      fluorescent labels for visualization of intracellular penetration and delivery of
      such microcapsules. Here, we describe an approach to design, fabricate, and
      characterize physico-chemical and functional properties of polyelectrolyte
      microcapsules encoded with water-solubilized and stabilized with three-functional
      polyethylene glycol derivatives core/shell QDs. Developed microcapsules were
      characterized by dynamic light scattering, electrophoretic mobility, scanning
      electronic microscopy, and fluorescence and confocal microscopy approaches,
      providing exact data on their size distribution, surface charge, morphological,
      and optical characteristics. The fluorescence lifetimes of the QD-encoded
      microcapsules were also measured, and their dependence on time after preparation
      of the microcapsules was evaluated. The optimal content of QDs used for encoding
      procedure providing the optimal fluorescence properties of the encoded
      microcapsules was determined. Finally, the intracellular microcapsule uptake by
      murine macrophages was demonstrated, thus confirming the possibility of efficient
      use of developed system for live cell imaging and visualization of microcapsule
      transportation and delivery within the living cells.

PMID- 29372481
TI  - The Importance of Muscular Strength: Training Considerations.
AB  - This review covers underlying physiological characteristics and training
      considerations that may affect muscular strength including improving maximal
      force expression and time-limited force expression. Strength is underpinned by a
      combination of morphological and neural factors including muscle cross-sectional
      area and architecture, musculotendinous stiffness, motor unit recruitment, rate
      coding, motor unit synchronization, and neuromuscular inhibition. Although single
      and multi-targeted block periodization models may produce the greatest strength
      power benefits, concepts within each model must be considered within the
      limitations of the sport, athletes, and schedules. Bilateral training, eccentric
      training and accentuated eccentric loading, and variable resistance training may
      produce the greatest comprehensive strength adaptations. Bodyweight exercise,
      isolation exercises, plyometric exercise, unilateral exercise, and kettlebell
      training may be limited in their potential to improve maximal strength but are
      still relevant to strength development by challenging time-limited force
      expression and differentially challenging motor demands. Training to failure may
      not be necessary to improve maximum muscular strength and is likely not necessary
      for maximum gains in strength. Indeed, programming that combines heavy and light
      loads may improve strength and underpin other strength-power characteristics.
      Multiple sets appear to produce superior training benefits compared to single
      sets; however, an athlete's training status and the dose-response relationship
      must be considered. While 2- to 5-min interset rest intervals may produce the
      greatest strength-power benefits, rest interval length may vary based an
      athlete's training age, fiber type, and genetics. Weaker athletes should focus on
      developing strength before emphasizing power-type training. Stronger athletes may
      begin to emphasize power-type training while maintaining/improving their
      strength. Future research should investigate how best to implement accentuated
      eccentric loading and variable resistance training and examine how initial
      strength affects an athlete's ability to improve their performance following
      various training methods.

PMID- 29372486
TI  - Usability and acceptance evaluation of ACESO: a Web-based breast cancer
      survivorship tool.
AB  - PURPOSE: The specific objective of this research is to design and develop a
      personalized Web application to support breast cancer survivors after treatment,
      as they deal with post-treatment challenges, such as comorbidities and side
      effects of treatment. METHODOLOGY: A mixed-methods approach, utilizing a
      combination of think-aloud analysis, personal interviews, and surveys, was
      adopted for user acceptance and usability testing among a group of breast cancer
      survivors. User feedback was gathered on their perceived value of the
      application, and any user-interface issues that may hinder the overall usability
      were identified. RESULTS: The application's portability and capability of
      organizing their entire breast cancer-related medical history as well as tracking
      various quality of life indicators were perceived to be valuable features. The
      application had an overall high usability; however, certain sections of the
      application were not as intuitive to locate. Visual elements of the website were
      appreciated; however, overall experience would benefit from incorporating more
      sociable elements that exhibit positive re-enforcement within the end user and
      provide a friendlier experience. CONCLUSION: The results of the study showcase
      the need for more personalized tools and resources to support survivors in self
      management. It also demonstrates the ability to integrate breast cancer
      survivorship care plans from diverse providers and paves the way to add further
      value-added features in consumer health applications, such as personal decision
      support. IMPLICATIONS FOR CANCER SURVIVORS: Using a personal decision support
      based tool can serve as a training tool and resource, providing these patients
      with pertinent information about the various aspects of their long-term health,
      while educating them about any related side effects and symptoms. It is hoped
      that making such tools more accessible could help in engaging survivors to play
      an active role in managing their health and encourage shared decision-making with
      their providers.

PMID- 29372484
TI  - Comparative impact of systemic delivery of atorvastatin, simvastatin, and
      lovastatin on bone mineral density of the ovariectomized rats.
AB  - PURPOSE: In addition to lipid-lowering properties, statins have been suggested to
      affect bone turnover by increasing the osteoblastic bone formation and blocking
      the osteoclastogenesis. However, there are many controversial reports regarding
      the beneficial effect of statins on osteoporosis. In this study, we investigated
      the therapeutic effects of the most important lipophilic statins administered
      orally for 60 days to the ovariectomized (OVX) female Sprague-Dawley rats and
      compared the effects on different harvested trabecular and compact bones.
      METHODS: Thirty female rats were divided into five equal groups including the
      normal rats, untreated OVX rats (negative control), and the OVX rats treated with
      atorvastatin (20 mg/kg/day), simvastatin (25 mg/kg/day), and lovastatin (20
      mg/kg/day). The osteoporotic animals were treated daily for 60 days and
      euthanized at the end of experiments. The effectiveness of these treatments was
      evaluated by biomechanical testing, histopathologic, histomorphometric, micro-CT
      scan, real-time PCR, and serum biochemical analysis. Moreover, the hepatotoxicity
      and rhabdomyolysis related with these treatments were assessed by biochemistry
      analysis and histopathological evaluation. RESULTS: The results and statistical
      analysis showed that systemic delivery of simvastatin and lovastatin
      significantly increased serum calcium level, expression of osteogenic genes, bone
      mineral density (BMD), and biomechanical properties in comparison to the
      untreated OVX rats, especially in trabecular bones (P < 0.05). The results of
      different analysis also indicated that there was no statistical difference
      between the atorvastatin-treated animals and the negative control. Among all
      treatments, only atorvastatin showed an evident hepatotoxicity and myopathy.
      CONCLUSIONS: It was concluded that the lovastatin and simvastatin efficiently
      ameliorated the OVX-induced osteoporosis. Moreover, the simvastatin-treated
      animals showed more resemblance to the normal group in terms of BMD, expression
      of osteogenic genes, serum biochemical parameters, histomorphometric findings,
      and biomechanical performance with no significant side-effects.

PMID- 29372487
TI  - Innovation and Integrity: Desiderata and Future Directions for Prevention and
      Intervention Science.
AB  - This article summarizes essential implications of the papers within this special
      issue and discusses directions for future prevention and intervention research on
      conceptual issues, methodological and transfer-related challenges and
      opportunities. We identify a need to move from programs to principles in
      intervention research and encourage the implementation of research on potential
      mechanisms underlying intervention effectiveness. In addition, current
      methodological issues in intervention research are highlighted, including
      advancements in methodology and statistical procedures, extended outcome
      assessments, replication studies, and a thorough examination of potential biases.
      We further discuss transfer-related issues, for example the need for more
      research on the flexibility and adaptability of programs and intervention
      approaches as well as more general problems in knowledge translation reasoning
      the need for enhanced communication between practitioners, policy makers, and
      researchers. Finally, we briefly touch on the need to discuss the relation
      between single intervention programs, the mental health system, and changes of
      contextual conditions at the macro level.

PMID- 29372488
TI  - JGIM Embraces Your Work on Substance Use.

PMID- 29372485
TI  - Consumer credit as a novel marker for economic burden and health after cancer in
      a diverse population of breast cancer survivors in the USA.
AB  - BACKGROUND: Consumer credit may reflect financial hardship that patients face due
      to cancer treatment, which in turn may impact ability to manage health after
      cancer; however, credit's relationship to economic burden and health after cancer
      has not been evaluated. METHODS: From May to September 2015, 123 women with a
      history of breast cancer residing in Pennsylvania or New Jersey completed a cross
      sectional survey of demographics, socioeconomic position, comorbidities, SF-12
      self-rated health, economic burden since cancer diagnosis, psychosocial stress,
      and self-reported (poor to excellent) credit quality. Ordinal logistic regression
      evaluated credit's contribution to economic burden and self-rated health.
      RESULTS: Mean respondent age was 64 years. Mean year from diagnosis was 11.5.
      Forty percent of respondents were Black or Other and 60% were White. Twenty-four
      percent self-reported poor credit, and 76% reported good to excellent credit
      quality. In adjusted models, changing income, using savings, borrowing money, and
      being unable to purchase a health need since cancer were associated with poorer
      credit. Better credit was associated with 7.72 ([1.22, 14.20], p = 0.02) higher
      physical health t-score, and a - 2.00 ([- 3.92, - 0.09], p = 0.04) point change
      in psychosocial stress. CONCLUSIONS: This exploratory analysis establishes the
      premise for consumer credit as a marker of economic burden and health for breast
      cancer survivors. Future work should validate these findings in larger samples
      and for other health conditions. IMPLICATIONS FOR CANCER SURVIVORS: Stabilizing
      and monitoring consumer credit may be a potential intervention point for
      mitigating economic burden after breast cancer.

PMID- 29372489
TI  - Reliability of the sliding scale for collecting affective responses to words.
AB  - Warriner, Shore, Schmidt, Imbault, and Kuperman, Canadian Journal of Experimental
      Psychology, 71; 71-88 (2017) have recently proposed a slider task in which
      participants move a manikin on a computer screen toward or further away from a
      word, and the distance (in pixels) is a measure of the word's valence. Warriner,
      Shore, Schmidt, Imbault, and Kuperman, Canadian Journal of Experimental
      Psychology, 71; 71-88 (2017) showed this task to be more valid than the widely
      used rating task, but they did not examine the reliability of the new
      methodology. In this study we investigated multiple aspects of this task's
      reliability. In Experiment 1 (Exps. 1.1-1.6), we showed that the sliding scale
      has high split-half reliability (r = .868 to .931). In Experiment 2, we also
      showed that the slider task elicits consistent repeated responses both within a
      single session (Exp. 2: r = .804) and across two sessions separated by one week
      (Exp. 3: r = .754). Overall, the slider task, in addition to having high
      validity, is highly reliable.

PMID- 29372490
TI  - A database of orthography-semantics consistency (OSC) estimates for 15,017
      English words.
AB  - Orthography-semantics consistency (OSC) is a measure that quantifies the degree
      of semantic relatedness between a word and its orthographic relatives. OSC is
      computed as the frequency-weighted average semantic similarity between the
      meaning of a given word and the meanings of all the words containing that very
      same orthographic string, as captured by distributional semantic models. We
      present a resource including optimized estimates of OSC for 15,017 English words.
      In a series of analyses, we provide a progressive optimization of the OSC
      variable. We show that computing OSC from word-embeddings models (in place of
      traditional count models), limiting preprocessing of the corpus used for inducing
      semantic vectors (in particular, avoiding part-of-speech tagging and
      lemmatization), and relying on a wider pool of orthographic relatives provide
      better performance for the measure in a lexical-processing task. We further show
      that OSC is an important and significant predictor of reaction times in visual
      word recognition and word naming, one that correlates only weakly with other
      psycholinguistic variables (e.g., family size, word frequency), indicating that
      it captures a novel source of variance in lexical access. Finally, some
      theoretical and methodological implications are discussed of adopting OSC as one
      of the predictors of reaction times in studies of visual word recognition.

PMID- 29372491
TI  - Problems Inherent to Augmentation of Natural Enemies in Open Agriculture.
AB  - Augmentation biological control has successfully replaced a lot of insecticide
      use in 'closed system' agriculture (e.g., greenhouses). The profitable
      commercialization of biocontrol agents in greenhouses has created an incentive to
      expand markets for mass-reared beneficial insects into open agricultural systems,
      often without sufficient scientific justification. However, the semi-contained
      nature of greenhouse culture is often critical to the success of augmentation and
      can serve to mask potential pitfalls and intrinsic limitations of this approach
      in open systems. Factors contributing to greenhouse successes include the reduced
      biological diversity of contained agroecosystems, the prevention of agent
      dispersal, the ability to maintain environmental conditions within a range
      favorable for the agent, the exclusion of competitors and natural enemies of the
      agent that might otherwise diminish its efficacy, and the absence of alternative
      prey/hosts that could divert predation/parasitism from the target pest. There are
      also problems arising from collection of source material from locally adapted
      populations, and the inadvertent imposition of artificial selection in the course
      of laboratory rearing. Besides highlighting these pitfalls, this paper aims to
      encourage more consideration of conservation approaches prior to investment in
      augmentation programs which entice farmers into perpetual cycles of 'rear and
      release.' I argue that although augmentation can benefit agriculture whenever it
      replaces pesticide applications, it does not constitute an ecologically
      sustainable solution because it requires continued inputs, and it can distract
      research attention away from more sustainable objectives. Sustainable biological
      control is best achieved through modifications to cultural practices that
      increasingly 'naturalize' agroecosystems, thus facilitating the natural
      recruitment and persistence of beneficial arthropod fauna, combined with habitat
      management geared to increasing overall plant and arthropod diversity in the
      agroecosystem.

PMID- 29372492
TI  - Doctor-pharmacist communication in hospitals: strategies, perceptions,
      limitations and opportunities.
AB  - : Background Effective communication between health professionals contributes to
      safe and efficient patient care, whereas communication breakdown can lead to
      adverse patient outcomes and increased healthcare expenditure. Information on how
      pharmacists and doctors communicate with each other in hospitals is limited.
      Objective To explore usage and perceptions of communication methods by doctors
      and pharmacists in hospital settings. Setting Four public hospitals in Australia.
      Method A mixed method study utilising a pilot questionnaire, semi-structured
      interviews, and electronic survey was designed. Frequentist statistics and
      logistic regression were used to analyse survey data. Thematic analysis was
      conducted to evaluate semi-structured interview data and free-text survey
      comments. MAIN OUTCOME MEASURES: Frequency of use of communication methods,
      perceptions of the convenience, time taken to use, accuracy and effectiveness of
      each method. Results More than 95% of doctors and pharmacists combined used face
      to-face and phone calls to communicate with each other, 70% used a medication
      management plan, and 62% used progress notes. A preference for oral communication
      was confirmed with the expressed need for building professional rapport and
      receiving responses. Perceptions regarding effectiveness of oral communication
      methods were related to perceptions of their convenience and accuracy.
      Professional groups described differences in perceived ownership of various modes
      of communication. Conclusions Preferences for oral communication create potential
      issues with recall and comprehension. Integrating oral communication features
      into written communication methods, e.g. creating responses, conversations,
      building rapport, may change doctors' and pharmacists' perceptions of
      effectiveness. Communication receipt and response functionality in electronic
      medication and record management systems may improve communication.

PMID- 29372493
TI  - The predictive potential of hyponatremia for glioblastoma patient survival.
AB  - Glioblastoma is a devastating malignancy with a dismal survival rate. Currently,
      there are limited prognostic markers of glioblastoma including IDH1, ATRX, MGMT,
      PTEN, EGFRvIII, and others. Although these biomarkers for tumor prognosis are
      available, a surgical biopsy must be performed for these analyses, which has
      morbidity involved. A non-invasive and readily available biomarker is sought
      after which provides clinicians prognostic information. Sodium is an electrolyte
      that is easily and quickly obtained through analysis of a patient's serum.
      Hyponatremia has been shown to have a predictive and negative prognostic
      indication in multiple cancer types, but the role of glioblastoma patients' serum
      sodium at the time of diagnosis in predicting glioblastoma patient survival has
      not been determined. We assessed whether hyponatremia at the time of glioblastoma
      diagnosis correlates to patient survival and show that in our cohort of 200
      glioblastoma patients, sodium, at any level, did not significantly correlate to
      glioblastoma survival, unlike what is seen in multiple other cancer types. We
      further demonstrate that inducing hyponatremia in an orthotopic murine model of
      glioblastoma has no effects on tumor progression and survival.

PMID- 29372494
TI  - Genetic structure and polymorphism analysis of Xinjiang Hui ethnic minority based
      on 21 STRs.
AB  - In the present study, we calculated the allelic frequencies and forensic
      descriptive parameters of Hui ethnic minority on the basis of 21 short tandem
      repeat (STR) loci aiming at understanding population structure better and
      enriching population genetic database. Bloodstain samples of 506 unrelated
      healthy Hui individuals in Xinjiang Uygur Autonomous Region were collected.
      Altogether 268 alleles were observed and the allelic frequencies ranged from
      0.0010 to 0.5306. The combined power of discrimination and the cumulative
      probability of exclusion of the 21 STR loci in Hui ethnic minority were
      0.9999999999999999999999998697 and 0.9999999968, respectively. Population data
      obtained manifested that the panel of 21 STR loci could provide robust genetic
      information for individual identification and paternity testing involved in
      forensic applications for Huis of Xinjiang Region. Furthermore, the present
      results of interpopulation differentiations, phylogenetic trees and principal
      component analysis which were conducted based on the overlapping 16 STR loci
      revealed that Hui group was genetically close to Xibe ethnic group and Han
      populations from different regions.

PMID- 29372495
TI  - Estimation of Cross-Immunity Between Drifted Strains of Influenza A/H3N2.
AB  - To determine the cross-immunity between influenza strains, we design a novel
      statistical method, which uses a theoretical model and clinical data on attack
      rates and vaccine efficacy among school children for two seasons after the 1968
      A/H3N2 influenza pandemic. This model incorporates the distribution of
      susceptibility and the dependence of cross-immunity on the antigenic distance of
      drifted strains. We find that the cross-immunity between an influenza strain and
      the mutant that causes the next epidemic is 88%. Our method also gives estimates
      of the vaccine protection against the vaccinating strain, and the basic
      reproduction number of the 1968 pandemic influenza.

PMID- 29372496
TI  - Discrete and Continuum Approximations for Collective Cell Migration in a Scratch
      Assay with Cell Size Dynamics.
AB  - Scratch assays are routinely used to study the collective spreading of cell
      populations. In general, the rate at which a population of cells spreads is
      driven by the combined effects of cell migration and proliferation. To examine
      the effects of cell migration separately from the effects of cell proliferation,
      scratch assays are often performed after treating the cells with a drug that
      inhibits proliferation. Mitomycin-C is a drug that is commonly used to suppress
      cell proliferation in this context. However, in addition to suppressing cell
      proliferation, mitomycin-C also causes cells to change size during the
      experiment, as each cell in the population approximately doubles in size as a
      result of treatment. Therefore, to describe a scratch assay that incorporates the
      effects of cell-to-cell crowding, cell-to-cell adhesion, and dynamic changes in
      cell size, we present a new stochastic model that incorporates these mechanisms.
      Our agent-based stochastic model takes the form of a system of Langevin equations
      that is the system of stochastic differential equations governing the evolution
      of the population of agents. We incorporate a time-dependent interaction force
      that is used to mimic the dynamic increase in size of the agents. To provide a
      mathematical description of the average behaviour of the stochastic model we
      present continuum limit descriptions using both a standard mean-field
      approximation and a more sophisticated moment dynamics approximation that
      accounts for the density of agents and density of pairs of agents in the
      stochastic model. Comparing the accuracy of the two continuum descriptions for a
      typical scratch assay geometry shows that the incorporation of agent growth in
      the system is associated with a decrease in accuracy of the standard mean-field
      description. In contrast, the moment dynamics description provides a more
      accurate prediction of the evolution of the scratch assay when the increase in
      size of individual agents is included in the model.

PMID- 29372497
TI  - Expectations for Return to Work After Workplace Injuries: The Relationship
      Between Estimated Time to Return to Work and Estimate Accuracy.
AB  - Purpose Worker's expectations for return to working have been found to relate to
      return-to-work (RTW) outcomes; however, it is unclear if this varies depending
      upon the expected time to RTW. To advance the understanding of the relationship
      between expectations and RTW, we set out to answer the following research
      questions: Are shorter estimated times to RTW more accurate than estimates that
      are longer of duration? In addition, we sought to determine if there was a point
      in time that coincides with RTW estimates no longer being reliably related to
      time to RTW. Methods We utilized workers' compensation data from a large, United
      States-based insurance company. Injured workers' (N = 15,221) expectations for
      returning to work were compared with the termination of their total temporary
      indemnity payments. A linear regression model was used to determine if shorter
      lengths of expected time to RTW were more accurate. Quantile regression modelling
      was used to determine if there was point at which the expected time to RTW no
      longer reliably relates to the actual time to RTW. Results Findings indicated a
      positive relationship such that as the number of expected days to RTW increased,
      the number of days of difference (estimate error) between the actual time to RTW
      and the expected time to RTW also increased (beta = 0.34, P < .001). The results
      of the quantile regression modelling indicated that for all quantiles estimated,
      with the exception of the quantile for estimates of 360 days, the relationship
      between the actual time to RTW and the expected time to RTW were statistically
      significant (P < .05). However, for RTW estimates of more than 14 days the
      relationship began decreasing in strength. Conclusion Results indicate that
      injured workers' expectations for RTW can be used for RTW forecasting purposes.
      However, it is the case that RTW events in the near future can be forecasted with
      higher accuracy than those that are more distant, and that in general, injured
      workers will underestimate how long it will take them to RTW.

PMID- 29372498
TI  - Pneumonic plague epidemic in Northeast China in 1910-1911: Dr. Wu Lien-Teh's
      epidemic preventive system for plague control.
AB  - Pneumonic plague that originated in Russian Siberia broke out in Northeast China
      in October 1910-March 1911. On the basis of field visits, autopsy,
      bacteriological identification, and close collaboration with local authorities
      and international colleagues, Dr. Wu Lien-Teh implemented a series of efficient
      antiplague measures, which successfully controlled the development of an
      extraordinary epidemic plague. In his subsequent work, Dr. Wu demonstrated the
      respiratory transmission of pneumonic plague and tarbagans' role in this spread.
      Dr.Wu's academic and cultural contributions are valuable in the medical progress
      in China.

PMID- 29372500
TI  - Examining the Impact of This Is My Brave on Mental Illness Stigma and Willingness
      to Seek Help: A Pilot Study.
AB  - This Is My Brave (TIMB) is a contact-based mental illness stigma reduction
      program, set in theaters, meant to reduce stigma, increase beliefs about
      empowerment and recovery, and improve attitudes towards treatment seeking for
      mental health concerns. The authors conducted the first empirical evaluation of
      TIMB using a pre-post survey design. Approximately 481 audience members of TIMB
      performances were invited to complete a survey of stigmatizing attitudes towards
      mental illness, beliefs about recovery and empowerment, and willingness to seek
      treatment at pre-and post-performance. Analyses of responses from 372
      participants using paired samples t-tests revealed changes in the desired
      direction on all variables from pre-test to post-test. Audience members
      experienced a decrease in stigma, improvements in beliefs about recovery and
      empowerment, and greater willingness to seek treatment. TIMB is a promising
      stigma-reduction program and there is a need for a more detailed investigation of
      the program's impact using more rigorous methodology.

PMID- 29372499
TI  - Prevalence and molecular characteristics of Listeria monocytogenes in cooked
      products and its comparison with isolates from listeriosis cases.
AB  - This study aimed to investigate the prevalence and molecular characteristics of
      Listeria monocytogenes in cooked products in Zigong City, China. The overall
      occurrence of the L. monocytogenes in the ready-to-eat (RTE) shops and mutton
      restaurants surveyed was 16.2% (141/873). An occurrence of 13.5% was observed in
      RTE pork, 6.5% in RTE vegetables, and more than 24.0% in either cooked mutton or
      cooked haggis. Serotype 1/2b (45.4%), 1/2a (33.3%), and 1/2c (14.2%) were the
      predominant types. By comparing the clonal complexes (CCs) based on multilocus
      sequence typing (MLST) of the L. monocytogenes from cooked foods in Zigong City
      and 33 listeriosis cases from different districts of China, CC87, CC9, CC8, and
      CC3 were showed to be prevalent in cooked products and CC87 and CC3 were the
      first two frequent types in the 33 clinic-source strains. All CC87 stains
      harbored the newly reported Listeria pathogenicity island 4 (LIPI-4) gene
      fragment ptsA, and all CC3 strains possessed the Listeria pathogenicity island 3
      (LIPI-3) gene fragment llsX. These may increase the occurrence of the strains
      belonging to CC87 and CC3 in listeriosis cases in China and also underline the
      risk of infection owing to the consumption of the cooked products from Zigong.
      ST619 (serotype 1/2b) harbored both llsX and ptsA, indicating a potential
      hypervirulent sequence type in Zigong.

PMID- 29372501
TI  - Validation of the Community Integration Scale for Adults with Psychiatric
      Disorders (CIS-APP-34).
AB  - The current focus on community integration of individuals with psychiatric
      problems is attracting an increasing interest in the psychological literature, as
      it is regarded as a favorable factor in the recovery and for the well-being of
      these individuals. The Community Integration Scale of Adults with Psychiatric
      Disorders (CIS-APP-34) is a self-report scale developed to assess community
      integration in several dimensions. The main goal of the current study is to
      explore the psychometric properties of CIS-APP-34 in a sample of 411 participants
      with and without a psychiatric illness, with ages between 19 and 91 years old,
      living in the Azores Islands, Portugal. A confirmatory factor analysis was
      carried out to confirm the latent structure of the scale, and a five-factor model
      has presented good fit indices. Further analysis showed that the CIS-APP-34 is a
      measure with good reliability, validity and discriminant ability.

PMID- 29372502
TI  - Invasive alien plant species dynamics in the Himalayan region under climate
      change.
AB  - Climate change will impact the dynamics of invasive alien plant species (IAPS).
      However, the ability of IAPS under changing climate to invade mountain
      ecosystems, particularly the Himalayan region, is less known. This study
      investigates the current and future habitat of five IAPS of the Himalayan region
      using MaxEnt and two representative concentration pathways (RCPs). Two invasive
      species, Ageratum conyzoides and Parthenium hysterophorus, will lose overall
      suitable area by 2070, while Ageratina adenophora, Chromolaena odorata and
      Lantana camara will gain suitable areas and all of them will retain most of the
      current habitat as stable. The southern Himalayan foothills will mostly conserve
      species ecological niches, while suitability of all the five species will
      decrease with increasing elevation. Such invasion dynamics in the Himalayan
      region could have impacts on numerous ecosystems and their biota, ecosystem
      services and human well-being. Trans-boundary response strategies suitable to the
      local context of the region could buffer some of the likely invasion impacts.

PMID- 29372503
TI  - Perception of One-Minute Preceptor (OMP) Model as a Teaching Framework among
      Pediatric Postgraduate Residents: A Feedback Survey.

PMID- 29372504
TI  - Predictors of Pre-operative Anxiety in Indian Children.
AB  - OBJECTIVE: To identify the predictors of pre-operative anxiety in school-going
      children in India. METHODS: A prospective observational study was done at a
      tertiary care teaching hospital. Children aged 7-12 y scheduled for elective
      surgery and their parents were enrolled. Pre-operative anxiety in children and
      parents was assessed using STAI-C and STAI-P questionnaires respectively. The
      child's anxiety in pre-op room, at the time of parental separation and induction
      of anesthesia were assessed using m-YPAS scale. Possible predictors of anxiety
      under 'individual', 'social' and 'healthcare' domains were analyzed using
      logistic regression. The quality of mask induction of anesthesia was assessed
      using Induction Compliance Checklist. RESULTS: Sixty children completed the study
      successfully. Receiver operating characteristic (ROC) curve indicted mYPAS score
      >= 30 (observed score) to identify children with high anxiety as identified by
      STAI-C >=37 (self-reported score). The incidence of high anxiety escalated from
      pre-operative time (48%) to the time of parental separation (72%) and increased
      further at anesthetic induction (95%). Parental anxiety (p = 0.03) and
      socioeconomic background (p = 0.03) were significant predictors of the child's
      pre-operative anxiety. The presence of >4 people at induction (p = 0.002), but
      not pre-operative anxiety, was found significantly more in children with poor
      quality of mask induction. CONCLUSIONS: The incidence of peri-operative anxiety
      in Indian children is significant. Parental anxiety and socioeconomic background
      were found significant predictors of high pre-operative anxiety in our set-up.

PMID- 29372505
TI  - Intravenous Cocaine Results in an Acute Decrease in Levels of Biomarkers of
      Vascular Inflammation in Humans.
AB  - Cocaine use causes significant cardiovascular morbidity from its hemodynamic
      effects. It is less clear whether cocaine promotes atherosclerosis. Vascular
      inflammation is one of the earliest steps in the pathophysiology of
      atherosclerosis. We hypothesized that cocaine results in an increase in
      inflammatory markers. Study objective was to measure the acute effects of
      intravenous cocaine on biomarkers of vascular inflammation. Eleven chronic
      cocaine users were enrolled. After a drug-free period, they received intravenous
      cocaine at 0.36 mg/kg dose in an in-hospital controlled environment. Serum levels
      of soluble CD40 ligand, monocyte chemoattractant protein-1, interleukin 6, and
      soluble intercellular adhesion molecule-1 were measured at baseline, 6 h, 24 h,
      and 6 days after cocaine challenge and at baseline for controls. After cocaine
      challenge, sCD40 ligand levels decreased in subjects and were significantly lower
      at 24 h. MCP-1 levels decreased and were significantly lower at the 6-day time
      point. No significant changes in IL-6 or sICAM-1 level were found. In conclusion,
      intravenous cocaine did not result in an increase in levels of inflammatory
      markers. Levels of MCP-1 and sCD40L decreased significantly. This unexpected
      finding suggests that chronic effects of cocaine on inflammation may be different
      from acute effects or that higher dosing may have differential effects as
      compared to lower dose used here.

PMID- 29372506
TI  - Tissue-Preferential Activity and Induction of the Pepper Capsaicin Synthase PUN1
      Promoter by Wounding, Heat and Metabolic Pathway Precursor in Tobacco and Tomato
      Plants.
AB  - A promoter is an essential structural component of a gene that controls its
      transcription activity in different development stages and in response to various
      environmental stimuli. Knowledge of promoter functionality in heterologous
      systems is important in the study of gene regulation and biotechnological
      application. In order to explore the activity of the pepper capsaicin synthase
      gene (PUN1) promoter, gene constructs of pPUN1::GUS (for beta-glucuronidase) and
      pPUN1::NtKED (for a tobacco wound-responsive protein) were introduced into
      tobacco and tomato, respectively, and their activities were examined. Higher
      levels of GUS staining intensity and transcription were detected in ovary, anther
      and pollen than other tissues or organs in tobacco plants. Likewise, transgenic
      tomato fruits had a higher level of pPUN1::NtKED gene expression than the leaf
      and flower. The PUN1-driven gene expression can be transiently induced by
      wounding, heat (40  degrees C) and the capsaicinoid biosynthetic pathway
      precursor phenylalanine. When compared to the reported pPUN1::GUS-expressing
      Arabidopsis, the PUN1 promoter exhibited a more similar pattern of activities
      among pepper, tobacco and tomato, all Solanaceae plants. Our results suggest the
      potential utility of this tissue-preferential and inducible promoter in other non
      pungent Solanaceae plants for research of gene function and regulation as well as
      in the biotechnological applications.

PMID- 29372507
TI  - Repeated liver stiffness measurement compared with paired liver biopsy in
      patients with non-alcoholic fatty liver disease.
AB  - INTRODUCTION: The value of repeated liver stiffness measurement (LSM) in non
      alcoholic fatty liver disease (NAFLD) has not been shown before. METHODS: A
      longitudinal study of biopsy-proven NAFLD patients was conducted at the Asian
      tertiary hospital from November 2012 to January 2017. Patients with paired liver
      biopsies and LSM were followed prospectively for liver-related and non-liver
      related complications, and survival. RESULTS: The data for 113 biopsy-proven
      NAFLD patients (mean age 51.3 +/- 10.6 years, male 50%) were analyzed. At
      baseline, advanced fibrosis based on histology and LSM was observed in 22 and
      46%, respectively. Paired liver biopsy and LSM at 1-year interval was available
      in 71 and 80% of patients, respectively. High-risk cases (defined as patients
      with advanced fibrosis at baseline who had no fibrosis improvement, and patients
      who developed advanced fibrosis on repeat assessment) were seen in 23 and 53% of
      patients, based on paired liver biopsy and LSM, respectively. Type 2 diabetes
      mellitus was independently associated with high-risk cases. The median follow-up
      was 37 months with a total follow-up of 328 person-years. High-risk cases based
      on paired liver biopsy had significantly higher rates of liver-related
      complications (p = 0.002) but no difference in other outcomes. High-risk patients
      based on paired LSM had a significantly higher rate of liver-related
      complications (p = 0.046), cardiovascular events (p = 0.025) and composite
      outcomes (p = 0.006). CONCLUSION: Repeat LSM can predict liver-related
      complications, similar to paired liver biopsy, and may be useful in identifying
      patients who may be at an increased risk of cardiovascular events. Further
      studies in a larger cohort and with a longer follow-up should be carried out to
      confirm these observations.

PMID- 29372508
TI  - Early candidate biomarkers found from urine of glioblastoma multiforme rat before
      changes in MRI.

PMID- 29372509
TI  - EARLY FLOWERING IN SHORT DAYS (EFS) regulates the seed size in Arabidopsis.
AB  - Post-transcriptional modifications, including histone modifications and DNA
      methylation, alter the chromatin landscape to regulate gene expression, thus
      control various cellular processes in plants. EARLY FLOWERING IN SHORT DAYS (EFS)
      is the major contributor for H3K36 methylation in Arabidopsis and is important
      for plant development. Here, we find that EFS is expressed in different stages of
      embryo morphogenesis, and the efs mutant produces larger embryo that results in
      enlarged seeds. Further analysis reveals that an imprinted gene MOP9.5 is
      hypomethylated at the promoter region and its expression is derepressed in efs
      mutant. MOP9.5 promoter is marked by various epigenetic modifications, and we
      find that following the increase of H3K36me3, H3K27me3 and H3K9me2 levels are
      reduced in efs mutant. This data indicates an antagonistic regulation between
      H3K36me3 and DNA methylation, and/or H3K27me3 at MOP9.5. Our results further show
      that both maternal and paternal EFS alleles are responsible for the seed size
      regulation, which unraveled a novel function of EFS in plant development.

PMID- 29372510
TI  - Responses of biotic interactions of dominant and subordinate species to decadal
      warming and simulated rotational grazing in Tibetan alpine meadow.
AB  - Warming increases competition among plant species in alpine communities by
      ameliorating harsh environmental conditions, such as low temperatures. Grazing,
      as the main human activity, may mitigate the effect of warming, as previously
      reported. However, it is critical to refine the effects of warming on biotic
      interactions among species, for example, by taking the competitive ability of
      species into consideration. Based on a 10-year warming and grazing experiment in
      a Tibetan alpine meadow, we evaluated interspecific biotic interactions of
      dominant and subordinate species, using the approach of interspecific spatial
      associations. Warming significantly increased competition between subordinate and
      dominant species as well as among subordinate species, but not among dominant
      species. Moreover, facilitation of dominant-subordinate species also increased
      under warming. Simulated rotational grazing had similar effects to warming, with
      increasing interspecific competition. Our results show that, when studying the
      effects of warming on biotic interactions among species, it is necessary to
      characterize different species pairs relative to their competitive ability, and
      that simulated rotational grazing does not mitigate the effects of warming in the
      long term. Our results also provide evidence that the spatial pattern of species
      is a critical mechanism in species coexistence.

PMID- 29372511
TI  - Plant non-coding RNAs and epigenetics.

PMID- 29372513
TI  - Representational coexistence in the God concept: Core knowledge intuitions of God
      as a person are not revised by Christian theology despite lifelong experience.
AB  - Previous research has shown that in the minds of young adult religious adherents,
      acquired theology about the extraordinary characteristics of God (e.g.,
      omniscience) coexists with, rather than replaces, an initial concept of God
      formed by co-option of the person concept. We tested the hypothesis that
      representational coexistence holds even after extensive experience with Christian
      theology, as indexed by age. Christian religious adherents ranging in age from 18
      to 87 years were asked to evaluate as true or false statements on which core
      knowledge intuitions about persons and Christian theology about God were
      consistent (both true or both false) or inconsistent (true on one and false on
      the other). Results showed, across adulthood, more theological errors in
      evaluating inconsistent versus consistent statements. Older adults also exhibited
      slower response times to inconsistent versus consistent statements. These
      findings show that despite extensive experience, indeed a lifetime of experience
      for some participants, the Christian theological God concept does not separate
      from the initial person concept from which it is formed. In fact, behavioral
      signatures of representational coexistence were not attenuated by experience. We
      discuss the broader implications of these findings to the acquisition of
      evolutionarily new concepts.

PMID- 29372512
TI  - Some further clarifications on age-related differences in Stroop interference.
AB  - Both the locus and processes underlying the age-related differences in Stroop
      interference are usually inferred from changes in magnitudes of standard (i.e.,
      overall) Stroop interference. Therefore, this study addressed these still-open
      issues directly. To this end, a sample of younger (18-26 years old) and healthy
      older (72-97 years old) was administered the semantic Stroop paradigm (that
      assesses the relative contribution of semantic compared to response conflict both
      of which contribute to overall Stroop interference) combined with a single-letter
      coloring and cuing (SLCC) procedure. Independently of an increased attentional
      focus on the relevant color dimension of Stroop words induced by SLCC (as
      compared to all letters colored and cued, ALCC), greater magnitudes of standard
      Stroop interference were observed in older (as compared to younger) adults. These
      differences were due to greater magnitudes of response conflict whereas
      magnitudes of semantic conflict remained significant and unchanged by healthy
      aging and SLCC. Thus, this direct evidence places the locus of age-related
      differences in Stroop interference at the level of response conflict (as opposed
      to semantic and/or both conflicts). In terms of processes underlying these
      differences, the reported evidence shows that both age-groups are equally
      (in)efficient in (a) focusing on the relevant color dimension and (b) suppressing
      the meaning of the irrelevant word-dimension of Stroop words. Healthy older
      adults are simply less efficient in suppressing the (pre-)response activity
      primed by the fully processed meaning of the irrelevant word-dimension. Standard
      interpretations of age-related differences in Stroop interference and a more
      general issue of how attentional selectivity actually operates in the Stroop task
      are therefore reconsidered in this paper.

PMID- 29372514
TI  - Gene cloning system for sulfonamide-mineralizing Microbacterium sp. strain BR1.
AB  - The wide application of sulfonamide (SA) antibiotics in human and veterinary
      medicine contributes to the accumulation of these antibiotics in the environment
      and the corresponding onset of antibiotic resistance among bacteria.
      Microbacterium sp. BR1 is capable of mineralizing sulfamethoxazole and other SAs
      via a novel mechanism. The genetic basis of SA elimination by BR1 remains
      unknown. Development of an efficient plasmid transfer protocol for Microbacterium
      sp. BR1 is highly desirable, as it would open the door to genetic analysis and
      manipulation of its genome. Here we report that intergeneric Escherichia coli
      Microbacterium spp. BR1 conjugation is an efficient way to introduce various
      plasmids into BR1. The generated transconjugants were stable in the presence of
      antibiotics and the plasmids showed no signs of rearrangements. Nevertheless, the
      plasmids were rapidly lost in the absence of selection. We also show that the
      cumate-inducible beta-glucuronidase reporter gene functions in BR1 and is
      strictly regulated. Our results set the working ground for further genetic
      manipulations of BR1, such as the overexpression of sulfonamide degradation genes
      or the selection of strong microbacterial promoters.

PMID- 29372516
TI  - A rare case of paradoxical embolism from tricuspid valve infective endocarditis
      and patent foramen ovale.

PMID- 29372515
TI  - Generation of transgenic chickens by the non-viral, cell-based method:
      effectiveness of some elements of this strategy.
AB  - Transgenic chickens have, in general, been produced by two different procedures.
      The first procedure is based on viral transfection systems. The second procedure,
      the non-viral method, is based on genetically modified embryonic cells
      transferred directly into the recipient embryo. In this review, we analyzed the
      effectiveness of important elements of the non-viral, cell-based strategy of
      transgenic chicken production. The main elements of this strategy are: isolation
      and cultivation of donor embryonic cells; transgene construction; cell
      transfection in vitro; and chimera production: injection of cells into recipient
      embryos, raising and identification of germline chimeras, mating germline
      chimeras, transgene inheritance, and transgene expression. In this overview,
      recent progress and important limitations in the development of transgenic
      chickens are presented.

PMID- 29372517
TI  - MiR-760 suppresses non-small cell lung cancer proliferation and metastasis by
      targeting ROS1.
AB  - MicroRNAs (miRNAs) have been shown to be critical regulators in many types of
      tumors. The aim of our study was to investigate the role of miR-760 in non-small
      cell lung cancer (NSCLC). We demonstrated that the expression of miR-760 was
      downregulated in NSCLC tissues compared with the adjacent normal tissues. We also
      demonstrated that the expression of miR-760 was downregulated in the NSCLC cell
      lines. Overexpression of miR-760 suppressed the NSCLC cell proliferation, cell
      cycle, and migration. Moreover, we identified that ROS1 was a direct target of
      miR-760 in the NSCLC cell. Elevated expression of miR-760 suppressed ROS1
      expression in the NSCLC cell. We also demonstrated that the expression of ROS1
      was higher in the NSCLC tissues than in the adjacent lung tissues. MiR-760
      expression level was reversely associated with the expression level of ROS1 in
      the NSCLC tissues. In summary, we showed that miR-760 suppressed the NSCLC cell
      proliferation, cell cycle, and migration through regulating the ROS1 expression.
      These data suggested that miR-760 may act as a tumor suppressor gene in the NSCLC
      partly through regulating ROS1 expression.

PMID- 29372519
TI  - Proposal for MSW contaminant classification applied to a tropical aquifer.
AB  - Groundwater is a natural resource exploited worldwide causing danger due to the
      lixiviation of waste deposited, which presents high potential degradation.
      Internationally, regulation aims for the maintenance of the quality of this
      resource. But the local lithology, mainly in countries with tropical weather, was
      not considered. This paper has an objective to propose two methodologies of
      contaminant identification of municipal solid waste (MSW) considering the
      Brazilian regulation, the local lithology and the temporal aspect. The study site
      is located in the midwest of Sao Paulo, at the Marilia Formation, Bauru Aquifer,
      which presents sandstone rich in calcite. At first, the historic monitoring data
      accumulated between 2002 and 2015 were statistically organized. Then,
      methodologies of classification of major constituents and contamination method
      were developed. After these analyses, the compounds that possibly cause anomaly
      in the local environment are Al, As, Ba, Ca, Cd, Co, Cr, Cu, phosphatic,
      nitrogenous, and sulfated compounds, Fe, K, Mn, Ni, and Pb. Some of these have
      lithogenic genesis typical of tropical environment, and others come from the
      disposed waste. Despite different approaches, both methods demonstrate efficiency
      in identifying the pollutants presenting distinctions among themselves in
      conjunction with actual local regulation and the lithogenic source of certain
      compounds.

PMID- 29372518
TI  - High efficacy of (Z)-gamma-bisabolene from the essential oil of Galinsoga
      parviflora (Asteraceae) as larvicide and oviposition deterrent against six
      mosquito vectors.
AB  - The eco-friendly management of mosquitoes with novel and effective larvicides and
      oviposition deterrents is a crucial challenge to prevent outbreaks of mosquito
      borne diseases. However, most of the herbal formulations tested in these years
      showed LC50 values higher of 40 ppm, and significant oviposition deterrent
      activity only when tested at relatively higher doses (> 50 MUg/ml). Herein, we
      studied the chemical composition of the Galinsoga parviflora essential oil (EO).
      This plant is an annual herb native to South America naturalized all over the
      world. We tested the EO larvicidal and oviposition deterrent action on 6 mosquito
      species. Totally 37 compounds were identified in the EO of G. parviflora by GC
      and GC-MS analyses. The major constituent was (Z)-gamma-bisabolene (38.9%). The
      G. parviflora EO and (Z)-gamma-bisabolene showed acute toxicity on An. stephensi
      (LC50 = 31.04 and 2.04 MUg/ml, respectively), Ae. aegypti (LC50 = 34.22 and 2.26
      MUg/ml, respectively), Cx. quinquefasciatus (LC50 = 37.10 and 2.47 MUg/ml,
      respectively), An. subpictus (LC50 = 40.97 and 4.09 MUg/ml, respectively), Ae.
      albopictus (LC50 = 45.55 and 4.50 MUg/ml, respectively) and Cx. tritaeniorhynchus
      (LC50 = 49.56 and 4.87 MUg/ml, respectively) larvae. Furthermore, the oviposition
      deterrent potential of the G. parviflora EO and (Z)-gamma-bisabolene was studied
      on six mosquito vectors, showing that 25 MUg/ml of (Z)-gamma-bisabolene led to an
      Oviposition Activity Index lower of - 0.79 in all tested mosquito vectors.
      Overall, all larvicidal LC50 values estimated for (Z)-gamma-bisabolene were lower
      than 5 MUg/ml. This result far encompasses current evidences of toxicity reported
      for the large majority of botanical products currently tested against mosquito
      young instars, allowing us to propose this compound as an highly effective
      mosquito larvicide and oviposition deterrent.

PMID- 29372521
TI  - Photocatalytic removal of SO2 using natural zeolite modified by TiO2 and
      polyoxypropylene surfactant.
AB  - Air pollution due to emission of various hazardous gases such as SO2 into the
      atmosphere and its control is an important environmental issue. Application of
      photocatalysts is considered as a suitable process to control the gaseous
      pollutants. In this study, the efficiency of clinoptilolite as a natural zeolite
      (Ze) modified by TiO2 (Ze-Ti) and a polymeric surfactant polyoxypropylene (Ze-Ti
      POP) for removal of SO2 was investigated. The nanocomposites were characterized
      by SEM, EDX, and BET analyses. The photocatalytic oxidation experiments of SO2 by
      the nanocomposites and natural zeolite were done under UV irradiation with
      initial SO2 concentration of 500 ppm in a photoreactor. The effects of different
      factors including reaction time, catalyst dose, UV irradiation intensity,
      humidity content, and calcination temperature and dose of TiO2 were studied. The
      modification of clinoptilolite by TiO2 and POP increased considerably the BET
      specific surface area of the nanocomposites. The results showed that maximum
      removal efficiencies of SO2 by Ze-Ti and Ze-Ti-POP under the optimum experimental
      conditions were 82.1 and 87.4%, respectively. Adsorption kinetics data well
      fitted with the Langmuir-Hinshelwood model. Moreover, reusing of nanocomposites
      after three regeneration cycles indicated that application of Ze-Ti and Ze-Ti-POP
      nanocomposites could be a promising approach for SO2 removal. Graphical abstract
      ?.

PMID- 29372520
TI  - Estimation of oxygen effective diffusion coefficient in a non-steady-state
      biofilm based on response time.
AB  - In wastewater treatment, oxygen effective diffusion coefficient (D eff ) is a key
      parameter in the study of oxygen diffusion-reaction process and mechanism in
      biofilms. Almost all the reported methods for estimating the D eff rely on other
      biokinetic parameters, such as substrate consumption rate and reaction rate
      constant. Then, the estimation was complex. In this study, a method independent
      of other biokinetic parameters was proposed for estimating the dissolved oxygen
      (DO) D eff in biofilms. It was based on the dynamic DO microdistribution in a non
      steady-state inactive biofilm, which was measured by the oxygen transfer modeling
      device (OTMD) combining with an oxygen microelectrode system. A pure DO diffusion
      model was employed, and the expression of the DO D eff was obtained by applying
      the analytical solution of the model to a selected critical DO concentration. DO
      D eff in the biofilm from the bioreactor was calculated as (1.054 +/- 0.041) * 10
      9 m2/s, and it was in the same order of magnitude with the reported results.
      Therefore, the method proposed in this study was effective and feasible. Without
      measurement of any other biokinetic parameters, this method was convenient and
      will benefit the study of oxygen transport-reaction process in biofilms and other
      biofouling deposits. Graphical abstract ?.

PMID- 29372522
TI  - Monitoring key organic indoor pollutants and their elimination in a biotrickling
      biofilter.
AB  - A biotrickling filter was evaluated to treat the air of the interior of a
      bioprocess research laboratory. Initially, various solid-phase microextraction
      (SPME) fibers were used to identify and quantify the volatile organic pollutants
      and hexane, methyl isobutyl ketone, benzene, toluene, and xylene were further
      selected as indicators due to their prevalence and relative abundance. The system
      treated organic loading rates between 0.16 mgcarbon m-3 h-1 and close to 30
      mgcarbon m-3 h-1 achieving removal efficiencies (RE) over 85% during 136
      operational days. Respirometry experiments demonstrated that moderate
      acidification (below 5.0), due to microbial activity, adversely affected
      biofilter performance and consequently pH control was necessary to maintain
      performance.

PMID- 29372523
TI  - In type 2 diabetes induced by cigarette smoking, activation of p38 MAPK is
      involved in pancreatic beta-cell apoptosis.
AB  - Type 2 diabetes (T2D) is a chronic disease caused by pancreatic beta-cell
      dysfunction and insulin resistance. Exposure to smoke is a risk factor for
      diabetes; however, its mechanisms are unclear. In an epidemiological study, we
      determined the relationship between cigarette smoking and beta-cell function. T2D
      patients had a history of heavier smoking than people without T2D, and heavy
      smokers had more abnormal glucose metabolism. For various smoking populations,
      there was a dose-effect relationship between decreases of homeostatic model
      assessment (HOMA)-beta levels or the increases of HOMA-insulin resistance (IR)
      levels and amount of smoking (pack-years), which indicated that smoking induced
      beta-cell dysfunction. For MIN6 cells, cigarette smoke extract (CSE) decreased
      insulin secretion and content; enhanced apoptosis, as illustrated by decreases of
      BCL-2 levels, increases of BAX and cleaved caspase-3 levels, and an increased
      apoptotic index; and activated the p38 MAPK pathway. For MIN6 cells, inhibition
      of p-p38 MAPK by SB203580 prevented enhanced apoptosis and the dysfunction of
      insulin secretion induced by CSE. In sum, activation of p38 MAPK is involved in
      the apoptosis of pancreatic beta-cells induced by cigarette smoking, which is a
      possible mechanism for induction of T2D by cigarette smoke.

PMID- 29372524
TI  - Temporal-spatial variation and partitioning of dissolved and particulate heavy
      metal(loid)s in a river affected by mining activities in Southern China.
AB  - The physicochemical properties and heavy metal(loid) concentrations of the river
      water both fluctuate greatly along the river affected by mining activities, and
      the transportation of heavy metal(loid)s is therefore more complicated than
      unpolluted river. Dissolved and particulate heavy metal(loid)s in a river
      polluted by mining activities were measured to study their temporal-spatial
      variation and partitioning. The concentrations of dissolved arsenic (As), cadmium
      (Cd), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were considerably
      high at the sites near the mine area. Notably, dissolved As at most sites were
      higher than the Chinese quality criterion of class II for surface water
      indicating high environmental risk. Mn and Pb at most sites and Ni at a part of
      the sites mainly existed in the particulate phase. For other heavy metal(loid)s,
      i.e., As, Cd, chromium (Cr), and Zn, the particulate phase was extremely high at
      the sites near the mine area and responsible for heavy metal(loid) transport.
      Significant correlations between particulate heavy metal(loid)s and temperature
      and electrical conductivity (EC) were found. However, the partitioning of heavy
      metal(loid)s did not significantly relate to the river water properties, due to
      most heavy metal(loid)s in suspended particulate matter (SPM) are stable and
      affected less by water properties. Except for Cr and Ni, other heavy metal(loid)s
      showed high concentrations in sediments, and considerable Cd, Mn, and Zn existed
      in exchangeable and carbonate fraction indicating high environmental risk. The
      environmental assessment of SPM showed that Cd, Zn, and As, as the main
      pollutants in SPM, all reached extremely polluted level at the sites near the
      mine area, and the environmental risk of heavy metal(loid)s in SPM was higher
      during dry season than that during wet season. The results can contribute to
      understanding the partitioning and transportation of heavy metal(loid)s in the
      river affected by mining activities.

PMID- 29372525
TI  - Development of porosity and surface chemistry of textile waste jute-based
      activated carbon by physical activation.
AB  - Two-step physical activation was used to prepare activated carbon from textile
      waste jute. Raw material was first carbonized under nitrogen and then activated
      by CO2. Based on yield and pore structure, the optimal carbonization temperature
      and time were 500  degrees C and 60 min, respectively. Carbonized sample was next
      activated. The development of porosity and surface chemistry was highly dependent
      on activation temperature and time. Activated carbon produced at 800  degrees C
      was predominantly microporous while that produced at 900  degrees C was more
      mesoporous and macroporous. The shift from microporosity to mesoporosity could be
      used to produce either microporous or mesoporous carbon just by changing the
      activation temperature. Activation also changed the surface chemistry and created
      a more carbonaceous structure. The jute-based activated carbon was mostly
      powdered in form, slightly acidic and effective in adsorbing both heavy metals
      and organics.

PMID- 29372526
TI  - Solar energy harvesting by magnetic-semiconductor nanoheterostructure in water
      treatment technology.
AB  - Photocatalytic degradation of toxic organic pollutants in the wastewater using
      dispersed semiconductor nanophotocatalysts has a number of advantages such as
      high activity, cost effectiveness, and utilization of free solar energy. However,
      it is difficult to recover and recycle nanophotocatalysts since the fine
      dispersed nanoparticles are easily suspended in waters. Furthermore, a large
      amount of photocatalysts will lead to color contamination. Thus, it is necessary
      to prepare photocatalysts with easy separation for the reusable application. To
      take advantage of high photocatalysis activity and reusability, magnetic
      photocatalysts with separation function were utilized. In this review, the
      photocatalytic principle, structure, and application of the magnetic
      semiconductor nanoheterostructure photocatalysts under solar light are evaluated.
      Graphical abstract ?.

PMID- 29372527
TI  - Impacts of urbanization on regional nonpoint source pollution: case study for
      Beijing, China.
AB  - Due to limits on available data, the effects of urban sprawl on regional nonpoint
      source pollution (NPS) have not been investigated over long time periods. In this
      paper, the characteristics of urban sprawl from 1999 to 2014 in Beijing were
      explored by analyzing historical land-use data. The Event Mean Concentration data
      have been collected from all available references, which were used to estimate
      the variation in urban NPSs. Moreover, the impacts of variation in urban sprawl
      on regional NPSs were qualified. The results indicated that the urbanization
      process showed different influences on pollutants, while COD and TN were
      identified as key NPS pollutants. Residential areas contributed more NPS
      pollutants than did roads, which played a tremendous role in the control of urban
      NPS. The results also suggested in part that the impact of urban sprawl on the
      variation of COD decreased while TN increased in Beijing during the study period.
      These results would provide insight into the impacts of urban sprawl on NPS
      variation over a long period, as well as the reference for reasonable urban
      planning directives.

PMID- 29372528
TI  - Hydration of dicalcium silicate and diffusion through neo-formed calcium-silicate
      hydrates at weathered surfaces control the long-term leaching behaviour of basic
      oxygen furnace (BOF) steelmaking slag.
AB  - Alkalinity generation and toxic trace metal (such as vanadium) leaching from
      basic oxygen furnace (BOF) steel slag particles must be properly understood and
      managed by pre-conditioning if beneficial reuse of slag is to be maximised. Water
      leaching under aerated conditions was investigated using fresh BOF slag at three
      different particle sizes (0.5-1.0, 2-5 and 10 * 10 * 20 mm blocks) and a 6-month
      pre-weathered block. There were several distinct leaching stages observed over
      time associated with different phases controlling the solution chemistry: (1)
      free-lime (CaO) dissolution (days 0-2); (2) dicalcium silicate (Ca2SiO4)
      dissolution (days 2-14) and (3) Ca-Si-H and CaCO3 formation and subsequent
      dissolution (days 14-73). Experiments with the smallest size fraction resulted in
      the highest Ca, Si and V concentrations, highlighting the role of surface area in
      controlling initial leaching. After ~2 weeks, the solution Ca/Si ratio (0.7-0.9)
      evolved to equal those found within a Ca-Si-H phase that replaced dicalcium
      silicate and free-lime phases in a 30- to 150-MUm altered surface region. V
      release was a two-stage process; initially, V was released by dicalcium silicate
      dissolution, but V also isomorphically substituted for Si into the neo-formed Ca
      Si-H in the alteration zone. Therefore, on longer timescales, the release of V to
      solution was primarily controlled by considerably slower Ca-Si-H dissolution
      rates, which decreased the rate of V release by an order of magnitude. Overall,
      the results indicate that the BOF slag leaching mechanism evolves from a
      situation initially dominated by rapid hydration and dissolution of primary
      dicalcium silicate/free-lime phases, to a slow diffusion limited process
      controlled by the solubility of secondary Ca-Si-H and CaCO3 phases that replace
      and cover more reactive primary slag phases at particle surfaces.

PMID- 29372529
TI  - Highly efficient degradation of berberine chloride form wastewater by a novel
      three-dimensional electrode photoelectrocatalytic system.
AB  - Fe2O3/graphite (Fe2O3/C) and nano-TiO2-coated glass bead were prepared by
      impregnation and sol-gel method respectively and employed as the catalyst of a
      novel three-dimensional electrode photoelectrocatalytic (3-D PEC) system. The
      photoexcited electrons can transfer from TiO2, Fe2O3 to counter electrode. It
      improves the migration of photoexcited charges, retards the fast recombination of
      electron-hole, and increases the lifetime of photogenerated holes (h+). In
      addition, the cycle reaction of Fe3+/Fe2+ on Fe2O3/C surface enhanced the Fenton
      reaction which can produce more hydroxyl radicals (.OH) and promote the capacity
      of mineralization of the pollutants. This novel 3-D PEC system showed excellent
      performance for the degradation of berberine chloride form (BCF). At the pH value
      of 3, 93% BCF was removed within 60 min; besides, 98.64% COD removal rate, 78.96%
      mineralization, 21.47% mineralization current efficiency, and just 3.16 kW h g
      1TOC energy cost were obtained in 120 min. In this study, we proposed the 3-D PEC
      mechanism. Electron spin resonance (ESR) and scavenging experiments suggest that
      the major reactive oxygen species (ROS) are superoxide radicals (O2.-), .OH, and
      h+, while the role of sulfate radical (SO4.-) is insignificant. This work
      provides a new dimension for the design of reactors for wastewater treatment and
      the construction of the 3-D PEC system can potentially be utilized in water
      purification.

PMID- 29372530
TI  - Preparation and characterization of Na2S-modified biochar for nickel removal.
AB  - Biochar has good adsorption ability to various contaminants. In this work, peanut
      shell, corncob, cotton stalks, and crayfish shell were pyrolyzed under three
      temperatures (300, 450, 600  degrees C) to obtain biochars for the removal of
      Ni2+. The biochars were further modified with 2 mol/L Na2S solution.
      Characterization results showed that the specific surface area and total pore
      volume of the modified biochars increased substantially. Among all the
      adsorbents, the modified corncob biochar (450  degrees C) showed the best Ni2+
      adsorption. The adsorption kinetics followed the Elovich model with an
      equilibrium time of 24 h. The maximum capacity of the modified biochar reached
      15.40 mg/g. The adsorption process was affected by pH, temperature, and
      coexisting ions. Increasing pH (under 7) provided more adsorption sites which
      enhanced adsorption capacity. Experimental results also indicated that the main
      adsorption mechanism of Ni2+ was ion exchange. Findings from this work suggest
      that modified biochar can be used as an effective adsorbent for the removal of
      Ni2+ from wastewater. Graphical abstract ?.

PMID- 29372531
TI  - The toxic nature of murine amylin and the immune responsivity of pancreatic islet
      to conformational antibody in mice.
AB  - The human amylin is a pancreatic peptide hormone found in hyperhormonemic state
      along with insulin in subclinical diabetes. Amylin has been associated with the
      pathology of type 2 diabetes, particularly due to its ability to assembly into
      toxic oligomers and amyloid specimens. On the other hand, some variants such as
      murine amylin has been described as non-amyloidogenic, either in vitro or in
      vivo. Recent data have demonstrated the amyloid propensity of murine amylin and
      the therapeutic analogue pramlintide, suggesting a universality for amylin
      amyloidosis. Here, we report the amyloidogenesis of murine amylin, which showed
      lower responsivity to the fluorescent probe thioflavin T compared to human
      amylin, but presented highly organized fibrilar amyloid material. The aggregation
      of murine amylin also resulted in the formation of cytotoxic specimens, as
      evaluated in vitro in INS-1 cells. The aggregation product from murine amylin was
      responsive to a specific antibody raised against amyloid oligomers, the A11
      oligomer antibody. Pancreatic islets of wild-type Swiss male mice have also shown
      responsivity for the anti-oligomer, indicating the natural abundance of such
      specimen in rodents. These data provide for the first time evidences for the
      toxic nature of oligomeric assemblies of murine amylin and its existence in wild
      type, non-transgenic mice.

PMID- 29372533
TI  - Visual attention shift to printed words during spoken word recognition in
      Chinese: The role of phonological information.
AB  - The aim of this study was to investigate the extent to which phonological
      information mediates the visual attention shift to printed Chinese words in
      spoken word recognition by using an eye-movement technique with a printed-word
      paradigm. In this paradigm, participants are visually presented with four printed
      words on a computer screen, which include a target word, a phonological
      competitor, and two distractors. Participants are then required to select the
      target word using a computer mouse, and the eye movements are recorded. In
      Experiment 1, phonological information was manipulated at the full-phonological
      overlap; in Experiment 2, phonological information at the partial-phonological
      overlap was manipulated; and in Experiment 3, the phonological competitors were
      manipulated to share either fulloverlap or partial-overlap with targets directly.
      Results of the three experiments showed that the phonological competitor effects
      were observed at both the full-phonological overlap and partial-phonological
      overlap conditions. That is, phonological competitors attracted more fixations
      than distractors, which suggested that phonological information mediates the
      visual attention shift during spoken word recognition. More importantly, we found
      that the mediating role of phonological information varies as a function of the
      phonological similarity between target words and phonological competitors.

PMID- 29372532
TI  - N-Acetyl-tryptophan glucoside (NATG) protects J774A.1 murine macrophages against
      gamma radiation-induced cell death by modulating oxidative stress.
AB  - Immune system is amongst the most radiosensitive system to radiation-induced
      cellular and molecular damage. Present study was focused on the evaluation of
      radioprotective efficacy of a novel secondary metabolite, N-acetyl tryptophan
      glucoside (NATG), isolated from a radioresistant bacterium Bacillus sp. INM-1
      using murine macrophage J774A.1 cells experimental model. Radioprotective
      efficacy of NATG against radiation-induced DNA damage and apoptosis was estimated
      using phosphatidyl-serine-externalization Annexin V-PI and Comet assay analysis.
      Radiation-induced cell death is the outcome of oxidative stress caused by free
      radicals. Therefore, perturbations in antioxidant enzymes i.e., superoxide
      dismutase (SOD), catalase, glutathione-s-transferase (GST) and GSH activities in
      irradiated and NATG pre-treated irradiated J774A.1 cells were studied. Results of
      the present study demonstrated that NATG pre-treated (0.25 ug/ml) irradiated (20
      Gy) cells showed significant (p < 0.05) reduction in apoptotic cells index at 4
      48 h as compared to radiation alone cells. Comet assay exhibited significant
      protection to radiation-induced DNA damage in J774A.1 cells. Significantly
      shortened DNA tail length, increased % Head DNA contents and lower olive tail
      moment was observed in NATG pre-treated irradiated cells as compared to radiation
      alone cells. Further, significant increase in catalase (~ 3.9 fold), SOD
      (67.52%), GST (~ 1.9 fold), and GSH (~ 2.5 fold) levels was observed in
      irradiated cells pre-treated with NATG as compared to radiation-alone cells. In
      conclusion, current study suggested that NATG pre-treatment to irradiated cells
      enhanced antioxidant enzymes in cellular milieu that may contribute to reduce
      oxidative stress and decrease DNA damage which resulted to significant reduction
      in the cell death of irradiated macrophages.

PMID- 29372534
TI  - Milk production and blood metabolites of dairy cattle as influenced by thermal
      humidity index.
AB  - The effects of high thermal stress on serum protein metabolites, milk production
      of transition dairy cows in semi-arid areas in South Africa were evaluated.
      Forty, +/- 8 months pregnant, Jersey heifers (+/- 26 months) in zero grazing
      management were selected during summer from two semi-arid communal areas. Summer
      thermal-humidity index (THI) of the areas were THI-1 (72-83: extreme caution) and
      THI-2 (75-87: danger). Blood samples were collected (21 days pre-partum, and 21
      and 75 days post-partum) and analysed for serum protein metabolites. Milk yield
      was recorded daily and samples collected for milk fat, protein, lactose and urea
      nitrogen analysis. Heifers in THI-2 had lower (P < 0.05) total serum proteins,
      albumin and blood urea nitrogen than THI-1. Post-calving, cows in THI-1 had
      higher (P < 0.05) TP (73.4 vs 67.9 g/l) and BUN (4.61 vs 3.77 mmol/l) at 21 DIM,
      and lower (P creatinine at 21 and 75 DIM than THI-2 group. Milk yield, fat and
      protein in THI-2 were all lower (P < 0.05) than THI-1 21DIM. The results confirm
      that heat stress affects utilisation of nutrients in transition dairy cows.

PMID- 29372535
TI  - PD-L1 and IDO1 Are Expressed in Poorly Differentiated Thyroid Carcinoma.
AB  - Poorly differentiated thyroid carcinoma (PDTC) is an aggressive form of thyroid
      cancer that currently has limited effective treatment options. Immune checkpoint
      inhibitors (ICIs) have shown to be an effective treatment for a variety of
      carcinomas. In this study, we explore whether immune checkpoint pathways, such as
      programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1),
      are activated in a cohort of patients with PDTC to determine whether ICIs may be
      an effective therapy for these patients. PDTC from 28 patients were stained for
      IDO1, PD-L1, and CD8 using immunohistochemistry. Staining was scored using an H
      score, and PD-L1 and IDO1 expression was correlated with clinicopathologic
      characteristics. Positivity for PD-L1 and IDO1 was set at an H-score cutoff of
      five. Twenty-five percent (n = 7/28) of the PDTC were positive for PD-L1
      expression. Twenty-nine percent (n = 2/7) of the PD-L1 positive PDTCs also co
      expressed IDO1. The expression of PD-L1 in PDTC was significantly associated with
      tumor size and multifocality, with a non-significant trend towards associations
      with older age, extrathyroidal extension, presence of metastasis, higher stage,
      increased number of CD8+ T cells, and decreased disease-free and overall
      survival. PD-L1 expression occurs in a subset of PDTC, and is associated with a
      subset of clinical features of aggressive thyroid disease. Given the limited
      effective treatments for this patient population, consideration for ICIs as
      monotherapy or in combination with an IDO1 inhibitor should be explored as a
      novel treatment modality for patients with PDTC.

PMID- 29372536
TI  - Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?
AB  - Eosinophilic esophagitis (EoE) is an immune-mediated, chronic esophageal disease
      characterized by esophageal symptoms and esophageal eosinophilia. It is triggered
      by foods and possibly by environmental allergens. Currently, there are no FDA
      approved therapies for EoE. Commonly used treatments include dietary restrictions
      and topical corticosteroids. Many of these therapies are suboptimal in their
      efficacy, have side effects, or diminish patients' quality of life. Biologic
      therapies for EoE have therefore been sought as an alternative. The mechanism by
      which food allergens trigger EoE is thought to be a T helper type 2 (Th2)
      reaction, resulting in secretion of the cytokines IL-4, IL-5, and IL-13. IL-5
      induces eosinophil production and trafficking to the esophagus, and IL-13 induces
      esophageal epithelial cells to secrete eotaxin-3, which drives eosinophil
      chemotaxis and activation. Mepolizumab and reslizumab, two anti-IL-5 antibodies,
      were studied in children and adults with EoE and resulted in reduction of
      esophageal tissue and blood eosinophils, but no significant reduction in
      symptoms. QAX576, an anti-IL-13 antibody, was studied in adults with EoE and
      showed a decrease in the esophageal eosinophil load and a trend towards clinical
      improvement. Since in situ IgE production was demonstrated in the EoE esophagus,
      omalizumab, an anti-IgE antibody, was studied in patients with EoE and not found
      to be overall beneficial. Furthermore, given the increased esophageal epithelial
      cell TNF-alpha expression in EoE, infliximab, an anti-TNF-alpha antibody, was
      studied in patients with EoE, with lack of success both clinically and
      histologically. In summary, although none of the biologicals studied so far in
      EoE have been highly effective, many demonstrated some histological benefit,
      especially those that targeted the Th2 axis. Therefore, the future for
      biologicals is promising as the pathophysiology of EoE is better understood,
      clinical assessment tools are validated, identification of patient subsets that
      respond best to biologicals is made, and dosages of biologicals are optimized.

PMID- 29372537
TI  - Sex and Management of Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic and progressive autoimmune disease more
      common in women than men (3:1). Although sex-based differences may play a complex
      role in promoting an autoimmune dysfunction, to date the comprehensive knowledge
      of the link between sex and RA is still partially lacking. Furthermore, males and
      females have been demonstrated to differently deal with their chronic
      pathologies, modifying the perceived sex-based burden of disease. Gender medicine
      is a newly approach focusing on the impact of gender differences on human
      physiology, pathophysiology, and clinical features of diseases, analyzing the
      complex interrelation and integration of sex and psychological and cultural
      behavior. A better comprehension of possible factors influencing sexual
      dimorphism in RA susceptibility, pattern of presentation, disease activity, and
      outcome could contribute to a tailored approach, in order to limit the morbidity
      of the disease. RA disease activity seems to be higher in women, whereas the
      response rate to synthetic and biologic disease-modifying therapies appears to be
      better in males. Moreover, the common strategies for RA management may be
      affected by concomitant pregnancy or childbearing desire, with particular regard
      to treatments with potential teratogenic effects or impact on fertility. Finally,
      comorbidities, such as fibromyalgia, major depression, and osteoporosis, are more
      frequent in females, while the impact of sex on cardiovascular risk is still
      controversial. Moving from the role of sex in influencing RA pathogenesis,
      epidemiology, and disease characteristics, this review explores the evidence on
      how sex can have an impact on strategies for managing patients with RA.

PMID- 29372539
TI  - Assessment of Plant-Probiotic Performance of Novel Endophytic Bacillus sp. in
      Talc-Based Formulation.
AB  - Endophytic bacteria are considered to have a plethora of plant growth promoting
      and anti-phytopathogenic traits to live within the plants. Hence, they have
      immense promises for plant probiotic development. In the current study, plant
      probiotic endophytic Bacillus sp. CaB5 which has been previously isolated from
      Capsicum annuum was investigated for its performance in talc-based formulation.
      For this, CaB5 was made into formulation with sterile talc, calcium carbonate,
      and carboxymethyl cellulose. The viability analysis of the formulation by
      standard plate count and fluorescence methods has confirmed the stable microbial
      count up to 45 days. Plant probiotic performance of the prepared formulation was
      analyzed on cowpea (Vigna unguiculata) and lady's finger (Abelmoschus
      esculentus). The results showed the formulation treatment to have enhancement
      effect on seed germination as well as plant growth in both selected plants. The
      results highlight the potential of CaB5-based formulation for field application
      to enhance growth of economically important plants.

PMID- 29372538
TI  - Sustained exenatide delivery via intracapsular microspheres for improved survival
      and function of microencapsulated porcine islets.
AB  - The ability of glucagon-like peptide-1 analogs to enhance glucose-dependent
      insulin secretion and to inhibit beta cell apoptosis could be of potential
      benefit for islet transplantation. In this study, we investigated the effect of
      sustained local delivery of exenatide, a synthetic exendin-4, on the in vitro
      viability and function of encapsulated porcine islets. Prior to encapsulation, we
      fabricated exenatide-loaded poly(latic-co-glycolic acid) microspheres, and
      investigated their release behavior with different initial drug-loading amounts.
      Exenatide-loaded microspheres, exhibiting a sustained release over 21 days, were
      subsequently chosen and co-encapsulated with porcine islets in alginate
      microcapsules. During the 21-day period, the islets co-encapsulated with the
      exenatide-loaded microspheres exhibited improved survival and glucose-stimulated
      insulin secretion, compared to those without. This suggested that the
      intracapsular sustained delivery of exenatide via microspheres could be a
      promising strategy for improving survival and function of microencapsulated
      porcine islets for islet xenotransplantation.

PMID- 29372540
TI  - Monitoring Microalgal Neutral Lipid Accumulation with Nile Red.
AB  - The widely applied Nile red (NR) method allows near real-time monitoring of
      microalgal neutral lipid accumulation. When added to a culture sample, optimally,
      the fluorescent dye NR penetrates the microalgal cell wall staining the
      intracellular neutral lipids, and the measured fluorescence is linearly
      correlated to the neutral lipid concentration. Here I describe an optimization
      protocol for determining the optimal staining parameters for each new microalgal
      species, followed by a basic NR staining protocol to be applied for monitoring of
      microalgal neutral lipid accumulation.

PMID- 29372541
TI  - The effects of a multicomponent intervention program on clinical outcomes
      associated with falls in healthy older adults.
AB  - BACKGROUND: Multicomponent intervention programs have been shown to be effective
      in reducing risk factors associated with falls, but the primary target population
      of these interventions is often low-functioning older adults. AIMS: The purpose
      of this study was to investigate the effectiveness of a multicomponent
      intervention program focusing on balance and muscle strength for independently
      functioning community-dwelling older adults. METHODS: Fifty-three independently
      functioning older adults, aged 80.09 +/- 6.62 years, participated in a group
      exercise class (conducted 2 times/week for 8 weeks) emphasizing balance. Outcome
      measures were balance performance using the Fullerton Advanced Balance (FAB)
      scale and muscle strength using the Senior Fitness Test (SFT). RESULTS: The
      intervention improved balance (P < 0.001), and older adults who were classified
      as having high fall risks based on the FAB scores at pre-testing improved more
      than older adults who were classified as having low fall risks (P = 0.017). As a
      result, 22 participants transitioned from a high fall risk group at pre-testing
      to a low fall risk group at post-testing (P < 0.001). The intervention also
      enhanced both upper and lower muscle extremity strength based on SFT results (P <
      0.001) regardless of participants' classification of fall risk status.
      CONCLUSIONS AND DISCUSSION: The multicomponent intervention conducted two times
      per week for 8 weeks was effective in improving balance and enhancing muscle
      strength of independently functioning older adults. The results underscore the
      importance of providing fall prevention interventions to healthy older adults, a
      population often not a target of balance interventions.

PMID- 29372543
TI  - Identification of chronic kidney disease risk in relatively lean Southern
      Chinese: the hypertriglyceridemic waist phenotype vs. anthropometric indexes.
AB  - PURPOSE: Assessing and comparing the ability of the hypertriglyceridemic waist
      (HW) phenotype and anthropometric obesity indexes to identify subjects at high
      risk of chronic kidney disease (CKD) in a relatively lean population in South
      China. METHODS: Using data from a community-based, cross-sectional study
      conducted in Zhuhai City, Southern China, we examined associations between the HW
      phenotype, anthropometric obesity indexes, and incident CKD risk in a relatively
      lean population. Multiple logistic regression analyses were used to evaluate the
      associations. RESULTS: The HW phenotype associated with CKD significantly in the
      unadjusted analysis (OR 3.53, 95% CI 1.65-7.52, P = 0.001). Further adjustment
      for gender, age, and other potential confounding variables had an impact on the
      odd ratios (OR); the OR decreased but still existed (OR 2.91, 95% 1.23-6.87, P =
      0.016). The association of the HW phenotype with CKD remained significant after
      further adjustment for hypertension and diabetes. No significant association
      between the anthropometric indexes and incident CKD was found. CONCLUSION: The HW
      phenotype, but not the anthropometric indexes, is associated with an elevated
      risk of CKD in relatively lean subjects. The HW phenotype appears to be a better
      predictor of CKD than the anthropometric indexes. LEVEL OF EVIDENCE: Level V,
      descriptive study.

PMID- 29372544
TI  - Drug Targets in Neurotrophin Signaling in the Central and Peripheral Nervous
      System.
AB  - Neurotrophins are a family of proteins that play an important role in the
      regulation of the growth, survival, and differentiation of neurons in the central
      and peripheral nervous system. Neurotrophins were earlier characterized by their
      role in early development, growth, maintenance, and the plasticity of the nervous
      system during development, but recent findings also indicate their complex role
      during normal physiology in both neuronal and non-neuronal tissues. Therefore, it
      is important to recognize a deficiency in the expression of neurotrophins, a
      major factor driving the debilitating features of several neurologic and
      psychiatric diseases/disorders. On the other hand, overexpression of
      neurotrophins is well known to play a critical role in pathogenesis of chronic
      pain and afferent sensitization, underlying conditions such as lower urinary
      tract symptoms (LUTS)/disorders and osteoarthritis. The existence of a redundant
      receptor system of high-and low-affinity receptors accounts for the diverse,
      often antagonistic, effects of neurotrophins in neurons and non-neuronal tissues
      in a spatial and temporal manner. In addition, studies looking at bladder
      dysfunction because of conditions such as spinal cord injury and diabetes
      mellitus have found alterations in the levels of these neurotrophins in the
      bladder, as well as in sensory afferent neurons, which further opens a new avenue
      for therapeutic targets. In this review, we will discuss the characteristics and
      roles of key neurotrophins and their involvement in the central and periphery
      nervous system in both normal and diseased conditions.

PMID- 29372545
TI  - Prospects of Cannabidiol for Easing Status Epilepticus-Induced Epileptogenesis
      and Related Comorbidities.
AB  - The hippocampus is one of the most susceptible regions in the brain to be
      distraught with status epilepticus (SE) induced injury. SE can occur from
      numerous causes and is more frequent in children and the elderly population.
      Administration of a combination of antiepileptic drugs can abolish acute seizures
      in most instances of SE but cannot prevent the morbidity typically seen in
      survivors of SE such as cognitive and mood impairments and spontaneous recurrent
      seizures. This is primarily due to the inefficiency of antiepileptic drugs to
      modify the evolution of SE-induced initial precipitating injury into a series of
      epileptogenic changes followed by a state of chronic epilepsy. Chronic epilepsy
      is typified by spontaneous recurrent seizures, cognitive dysfunction, and
      depression, which are associated with persistent inflammation, significantly
      waned neurogenesis, and abnormal synaptic reorganization. Thus, alternative
      approaches that are efficient not only for curtailing SE-induced initial brain
      injury, neuroinflammation, aberrant neurogenesis, and abnormal synaptic
      reorganization but also for thwarting or restraining the progression of SE into a
      chronic epileptic state are needed. In this review, we confer the promise of
      cannabidiol, an active ingredient of Cannabis sativa, for preventing or easing SE
      induced neurodegeneration, neuroinflammation, cognitive and mood impairments, and
      the spontaneous recurrent seizures.

PMID- 29372546
TI  - Neural Crest Stem-Like Cells Non-genetically Induced from Human Gingiva-Derived
      Mesenchymal Stem Cells Promote Facial Nerve Regeneration in Rats.
AB  - Non-genetic induction of somatic cells into neural crest stem-like cells (NCSCs)
      is promising for potential cell-based therapies for post-traumatic peripheral
      nerve regeneration. Here, we report that human gingiva-derived mesenchymal stem
      cells (GMSCs) could be reproducibly and readily induced into NCSCs via non
      genetic approaches. Compared to parental GMSCs, induced NCSC population had
      increased expression in NCSC-related genes and displayed robust differentiation
      into neuronal and Schwann-like cells. Knockdown of the expression of Yes
      associated protein 1 (YAP1), a critical mechanosensor and mechanotransducer,
      attenuated the expression of NCSC-related genes; specific blocking of RhoA/ROCK
      activity and non-muscle myosin II (NM II)-dependent contraction suppressed YAP1
      and NCSC-related genes and concurrently abolished neural spheroid formation in
      NCSCs. Using a rat model of facial nerve defect, implantation of NCSC-laden nerve
      conduits promoted functional regeneration of the injured nerve. These promising
      findings demonstrate that induced NCSCs derived from GMSCs represent an easily
      accessible and promising source of neural stem-like cells for peripheral nerve
      regeneration.

PMID- 29372548
TI  - Hand, foot and mouth disease in an adult.

PMID- 29372547
TI  - Impairment of Novel Object Recognition Memory and Brain Insulin Signaling in
      Fructose- but Not Glucose-Drinking Female Rats.
AB  - Excessive sugar intake has been related to cognitive alterations, but it remains
      unclear whether these effects are related exclusively to increased energy intake,
      and the molecular mechanisms involved are not fully understood. We supplemented
      Sprague-Dawley female rats with 10% w/v fructose in drinking water or with
      isocaloric glucose solution for 7 months. Cognitive function was assessed through
      the Morris water maze (MWM) and the novel object recognition (NOR) tests. Plasma
      parameters and protein/mRNA expression in the frontal cortex and hippocampus were
      determined. Results showed that only fructose-supplemented rats displayed
      postprandial and fasting hypertriglyceridemia (1.4 and 1.9-fold, p < 0.05) and a
      significant reduction in the discrimination index in the NOR test, whereas the
      results of the MWM test showed no differences between groups. Fructose-drinking
      rats displayed an abnormal glucose tolerance test and impaired insulin signaling
      in the frontal cortex, as revealed by significant reductions in insulin receptor
      substrate-2 protein levels (0.77-fold, p < 0.05) and Akt phosphorylation (0.72
      fold, p < 0.05), and increased insulin-degrading enzyme levels (1.86-fold, p <
      0.001). Fructose supplementation reduced the expression of antioxidant enzymes
      and altered the amount of proteins involved in mitochondrial fusion/fission in
      the frontal cortex. In conclusion, cognitive deficits induced by chronic liquid
      fructose consumption are not exclusively related to increased caloric intake and
      are correlated with hypertriglyceridemia, impaired insulin signaling, increased
      oxidative stress and altered mitochondrial dynamics, especially in the frontal
      cortex.

PMID- 29372549
TI  - Pancoast's syndrome: an unusual presentation of invasive pneumococcal disease.

PMID- 29372550
TI  - Analysis of Compounds Dissolved in Nonpolar Solvents by Electrospray Ionization
      on Conductive Nanomaterials.
AB  - Electrospray ionization mass spectrometry (ESI-MS) technique has limitations in
      analysis of compounds that are dissolved in nonpolar solvents. In this study,
      ambient ionization of compounds in solvents that are not "friendly" to
      electrospray ionization, such as n-hexane, is achieved by conductive
      nanomaterials spray ionization (CNMSI) on nanomaterial emitters, including carbon
      nanotubes paper and mesodendritic silver covered metal, which applies high
      voltages to emitters made of these materials without the assistance of polar
      solvents. Although the time intensity curves (TIC) commonly vary from 4.5% to
      23.7% over analyses, protonated molecular ions were found to be the most abundant
      species, demonstrating good reproducibility of the technique in terms of ionized
      species. Higher mass spectrometric responses are observed in analyzing nonpolar
      systems than polar systems. 2-Methoxyacetophenone, 4-methylacetophenone,
      benzothiazole, quinolone, and cycloheptanone as low as 2 pg in n-hexane can be
      directly detected using the developed method. The developed technique expands the
      analysis capability of ESI-MS for direct, online analysis of nonpolar systems,
      such as low polarity extracts, normal phase liquid chromatography eluates, and
      synthetic mixtures. Graphical Abstract.

PMID- 29372551
TI  - Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain.
AB  - Neuropeptides are structurally highly diverse messenger molecules that act as
      regulators of many physiological processes such as development, metabolism,
      reproduction or behavior in general. Differentiation of neuropeptidergic cells
      often corresponds with the presence of the transcription factor DIMMED. In the
      central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly
      occurs in neuroendocrine neurons that release peptides as neurohormones but also
      in interneurons with complex branching patterns. Fly strains with green
      fluorescence protein (GFP)-expressing dimmed cells make it possible to
      systematically analyze the processed neuropeptides in these cells. In this study,
      we mapped individual GFP-expressing neurons of adult D. melanogaster from the
      dimmed (c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types
      of dimmed neurons from the brain/gnathal ganglion. These cells included
      neuroendocrine cells with projection into the retrocerebral complex but also a
      number of large interneurons. Resulting mass spectra not only provided
      comprehensive data regarding mature products from 13 neuropeptide precursors but
      also evidence for the cellular co-localization of neuropeptides from different
      neuropeptide genes. The results can be implemented in a neuroanatomical map of
      the D. melanogaster brain. Graphical Abstract ?.

PMID- 29372552
TI  - Characterization of Disulfide-Linked Peptides Using Tandem Mass Spectrometry
      Coupled with Automated Data Analysis Software.
AB  - Disulfide bond formation is critical for maintaining structure stability and
      function of many peptides and proteins. Mass spectrometry has become an important
      tool for the elucidation of molecular connectivity. However, the interpretation
      of the tandem mass spectral data of disulfide-linked peptides has been a major
      challenge due to the lack of appropriate tools. Developing proper data analysis
      software is essential to quickly characterize disulfide-linked peptides. A
      thorough and in-depth understanding of how disulfide-linked peptides fragment in
      mass spectrometer is a key in developing software to interpret the tandem mass
      spectra of these peptides. Two model peptides with inter- and intra-chain
      disulfide linkages were used to study fragmentation behavior in both collisional
      activated dissociation (CAD) and electron-based dissociation (ExD) experiments.
      Fragments generated from CAD and ExD can be categorized into three major types,
      which result from different S-S and C-S bond cleavage patterns. DiSulFinder is a
      computer algorithm that was newly developed based on the fragmentation observed
      in these peptides. The software is vendor neutral and capable of quickly and
      accurately identifying a variety of fragments generated from disulfide-linked
      peptides. DiSulFinder identifies peptide backbone fragments with S-S and C-S bond
      cleavages and, more importantly, can also identify fragments with the S-S bond
      still intact to aid disulfide linkage determination. With the assistance of this
      software, more comprehensive disulfide connectivity characterization can be
      achieved. Graphical Abstract ?.

PMID- 29372553
TI  - Using Gas Phase Reactions of Hexamethylene Triperoxide Diamine (HMTD) to Improve
      Detection in Mass Spectrometry.
AB  - Our efforts to lower the detection limits of hexamethylene triperoxide diamine
      (HMTD) have uncovered previously unreported gas-phase reactions of primary and
      secondary amines with one of the six methylene carbons. The reaction occurs
      primarily in the atmospheric pressure chemical ionization (APCI) source and is
      similar to the behavior of alcohols with HMTD [1]. However, unlike alcohols, the
      amine reaction conserves the hydrogen peroxide on the intact product.
      Furthermore, with or without amines, HMTD is oxidized to tetramethylene
      diperoxide diamine dialdehyde (TMDDD) in a temperature-dependent fashion in the
      APCI source. Synthesized TMDDD forms very strong adducts (not products) to
      ammonium and amine ions in the electrospray ionization (ESI) source. Attempts to
      improve HMTD detection by generating TMDDD in the APCI source with post-column
      addition of amines were not successful. Signal intensity of the solvent related
      HMTD product in methanol, [HMTD+MeOH2-H2O2]+ (m/z 207.0975), was understandably
      related to the amount of methanol in the HMTD environment as it elutes into the
      source. With conditions optimized for this product, the detection of 100 pg on
      column was accomplished with a robust analysis of 300 pg (1.44 pmol) routinely
      performed on the Orbitrap mass spectrometers. Graphical Abstract ?.

PMID- 29372554
TI  - An Orbital Trap Mass Analyzer Using a Hybrid Magnetic-Electric Field: A
      Simulation Study.
AB  - An orbital ion trap mass analyzer employing hybrid magnetic-electric field was
      designed and simulated. The trap has a rotational symmetrical structure and the
      hybrid trapping field was created in a toroidal space between 12 pairs of sector
      detection electrodes. Ion injection and ion orbital motion inside the trap were
      simulated using SIMION 8.1 with a user Lua program, and the required electric and
      magnetic field were investigated. The image charge signal can be picked up by the
      12 pairs of detection electrodes and the mass resolution was evaluated using FFT.
      The simulated resolving power for the optimized configuration over 79,000 FWHM
      was obtained at the magnetic induction intensity of 0.5 Tesla in the simulation.
      Graphical Abstract ?.

PMID- 29372555
TI  - Gamma Knife Radiosurgery for Hemorrhagic Brainstem Cavernomas.
AB  - AIM: Effectiveness and safety of gamma knife radiosurgery (GKRS) for hemorrhagic
      brainstem cavernous malformations (BSCM) is still an unresolved problem. The
      purpose of this study was to assess treatment results of GKRS for hemorrhagic
      BSCMs. MATERIAL AND METHODS: A retrospective review was performed of patients
      with hemorrhagic BSCMs who were treated at the Acibadem Kozyatagi Hospital GKRS
      unit from May 2007 to October 2015. RESULTS: In total 82 patients were
      identified. All patients had experienced at least one hemorrhagic event (range 1
      3) and all of them presented radiological evidence of hemorrhage. The median
      target volume was 0,3 mL, and the median marginal radiation dose was 12 Gy. The
      mean durations before and after surgery were 25,5 (range 1-204) months and 50,3
      (range 13-113) months respectively. Pretreatment hemorrhage rates were calculated
      from the date of first hemorrhage to the date of radiosurgery. There were 97
      bleeds over 174.4 patient-years during the observation period, with an annual
      hemorrhage rate of 55.7 %. If the first bleed is excluded, the annual hemorrhage
      rate was 8.6%. Only three patients demonstrated rebleeding, which occurred at
      3,12 and 79 months after radiosurgery. Over a total follow up time of 344 patient
      years the annual rebleeding rate was therefore 0,87 %, indicating that the risk
      of BSCM hemorrhage was significantly decreased by radiosurgery. CONCLUSION: In
      this study GKRS was a safe and effective treatment for symptomatic low volume
      BSCMs when using a low marginal dose. A randomized controlled trial is needed
      that compares GKRS to observation if we are to establish the true efficacy of
      this treatment.

PMID- 29372556
TI  - Cutaneous non-tuberculous mycobacteria in Western Sydney, Australia. Population
      study 1996-2013.

PMID- 29372557
TI  - Mesenchymal stem cells promote cell invasion and migration and autophagy-induced
      epithelial-mesenchymal transition in A549 lung adenocarcinoma cells.
AB  - Mesenchymal stem cells (MSCs) are recruited into the tumour microenvironment and
      promote tumour growth and metastasis. Tumour microenvironment-induced autophagy
      is considered to suppress primary tumour formation by impairing migration and
      invasion. Whether these recruited MSCs regulate tumour autophagy and whether
      autophagy affects tumour growth are controversial. Our data showed that MSCs
      promote autophagy activation, reactive oxygen species production, and epithelial
      mesenchymal transition (EMT) as well as increased migration and invasion in A549
      cells. Decreased expression of E-cadherin and increased expression of vimentin
      and Snail were observed in A549 cells cocultured with MSCs. Conversely, MSC
      coculture-mediated autophagy positively promoted tumour EMT. Autophagy inhibition
      suppressed MSC coculture-mediated EMT and reduced A549 cell migration and
      invasion slightly. Furthermore, the migratory and invasive abilities of A549
      cells were additional increased when autophagy was further enhanced by rapamycin
      treatment. Taken together, this work suggests that microenvironments containing
      MSCs can promote autophagy activation for enhancing EMT; MSCs also increase the
      migratory and invasive abilities of A549 lung adenocarcinoma cells. Mesenchymal
      stem cell-containing microenvironments and MSC-induced autophagy signalling may
      be potential targets for blocking lung cancer cell migration and invasion.

PMID- 29372558
TI  - The association between multiple pilomatrixomas and APC gene mutations.

PMID- 29372559
TI  - Are all Xq26.2 duplications overlapping GPC3 on array-CGH a cause of Simpson
      Golabi-Behmel syndrome? When do we need transcript analysis?

PMID- 29372560
TI  - Inhibition of the CSF-1 receptor sensitizes ovarian cancer cells to cisplatin.
AB  - Ovarian cancer is one of the most common female malignancies, and cisplatin-based
      chemotherapy is routinely used in locally advanced ovarian cancer patients.
      Acquired or de novo cisplatin resistance remains the barrier to patient survival,
      and the mechanisms of cisplatin resistance are still not well understood. In the
      current study, we found that colony-stimulating-factor-1 receptor (CSF-1R) was
      upregulated in cisplatin-resistant SK-OV-3 and CaoV-3 cells. Colony-stimulating
      factor-1 receptor knockdown suppressed proliferation and enhanced apoptosis in
      cisplatin-resistant SK-OV-3 and CaoV-3 cells. However, CSF-1R overexpression had
      inverse effects. While parental SK-OV-3 and CaoV-3 cells were more resistant to
      cisplatin after CSF-1R overexpression, CSF-1R knockdown in SK-OV-3 and CaoV-3
      cells promoted cisplatin sensitivity. Overexpression and knockdown studies also
      showed that CSF-1R significantly promoted active AKT and ERK1/2 signalling
      pathways in cisplatin-resistant cells. Furthermore, a combination of cisplatin
      and CSF-1R inhibitor effectively inhibited tumour growth in xenografts. Taken
      together, our results provide the first evidence that CSF-1R inhibition can
      sensitize cisplatin-refractory ovarian cancer cells. This study may help to
      increase understanding of the molecular mechanisms underlying cisplatin
      resistance in tumours.

PMID- 29372561
TI  - Is It Time for Going Beyond the P-Value Paradigm With the Estimation of the
      Probability of Clinical Benefit as a Criterion for Assessing the Outcomes of a
      Clinical Trial? A Case Study in Patients With Major Depressive Disorder.
AB  - The conventional statistical methodologies for evaluating treatment effect are
      based on hypothesis testing (P-value). Alternative measurements of treatment
      effect have been proposed for anti-infective treatments using the probability of
      target attainment. A general framework is proposed to extend this methodology to
      other therapeutic areas. A disease trial model is used for estimating the
      probability of reaching a treatment effect associated with relevant clinical
      benefits, in complement to the evaluation of the probability of rejecting the
      null hypothesis. A case study is presented in depression, where disease status is
      evaluated using bounded clinical scores (Hamilton Depression Rating Scale), and
      detectable treatment effect is inversely proportional to placebo response. The
      beta-regression approach is used to model Hamilton scale scores, and a placebo
      related criterion is proposed for determining the clinical benefit. The
      probability of reaching a clinical benefit represents a reliable criterion for
      replacing the P-value paradigm in the assessment of the outcomes of clinical
      trials.

PMID- 29372562
TI  - Tylosis associated with squamous cell carcinoma of the oesophagus (TOC): Report
      of an African family with a novel RHBDF2 variant.

PMID- 29372563
TI  - Cladosporium cladosporioides-complex infection in a mixed-breed dog.
AB  - A 3-year-old female mixed-breed dog was referred with a 2-day history of serious
      dyspnea, coughing, lethargy, anorexia, and a low-grade right anterior lameness.
      At presentation, the dog had an increased respiratory rate, dull heart and lung
      sounds, and cyanotic mucous membranes. It was hyperthermic and slightly
      dehydrated. Laboratory findings showed mild neutrophilia with a left shift, while
      serum biochemistry variables were in the normal range. However, urinalysis
      revealed mild proteinuria and rare erythrocytes and leukocytes on sediment
      examination. Thoracic radiographs showed a diffuse mixed interstitial and
      alveolar pattern with an air bronchogram, while appendicular radiographs showed a
      right humeral interrupted brush-like periosteal reaction. Thoracic
      ultrasonography revealed mediastinal lymph node enlargement. Cytology from a fine
      needle aspirate of mediastinal lymph nodes revealed a pyogranulomatous
      lymphadenitis with numerous fungal hyphae. Culture on Sabouraud dextrose agar
      isolated dark fungal colonies with microscopic features consistent with
      Cladosporium spp. Sequencing of the internal transcribed spacer region identified
      the fungus as a species of the Cladosporium cladosporioides-complex.

PMID- 29372564
TI  - Optimal Birth Spacing: What Can We Measure and What Do We Want to Know?

PMID- 29372565
TI  - Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic
      pain syndrome.
AB  - BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a
      common disorder in which the two main clinical features are pelvic pain and lower
      urinary tract symptoms. There are currently many approaches for its management,
      using both pharmacological and non-pharmacological interventions. The National
      Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a
      validated measure commonly used to measure CP/CPPS symptoms. OBJECTIVES: To
      assess the effects of non-pharmacological therapies for chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS). SEARCH METHODS: We performed
      a comprehensive search using multiple databases, trial registries, grey
      literature and conference proceedings with no restrictions on the language of
      publication or publication status. The date of the latest search of all databases
      was August 2017. SELECTION CRITERIA: We included randomised controlled trials.
      Inclusion criteria were men with a diagnosis of CP/CPPS. We included all
      available non-pharmacological interventions. DATA COLLECTION AND ANALYSIS: Two
      review authors independently classified studies and abstracted data from the
      included studies, performed statistical analyses and rated quality of evidence
      (QoE) according to the GRADE methods. MAIN RESULTS: We included 38 unique studies
      with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies,
      204 participants) based on short-term follow-up, acupuncture reduces prostatitis
      symptoms in an appreciable number of participants compared with sham procedure
      (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI)
      -7.32 to -4.26, high QoE). Acupuncture likely results in little to no difference
      in adverse events (moderate QoE). It probably also decreases prostatitis symptoms
      compared with standard medical therapy in an appreciable number of participants
      (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, moderate QoE).2.
      Circumcision: (one study, 713 participants) based on short-term follow-up, early
      circumcision probably decreases prostatitis symptoms slightly (NIH-CPSI score MD 
      3.00, 95% CI -3.82 to -2.18, moderate QoE) and may not be associated with a
      greater incidence of adverse events compared with control (a waiting list to be
      circumcised, low QoE).3. Electromagnetic chair: (two studies, 57 participants)
      based on short-term follow-up, we are uncertain of the effects of the use of an
      electromagnetic chair on prostatitis symptoms. It may be associated with a
      greater incidence of adverse events compared with sham procedure (low to very low
      QoE).4. Lifestyle modifications: (one study, 100 participants) based on short
      term follow-up, lifestyle modifications may be associated with a greater
      improvement in prostatitis symptoms in an appreciable number of participants
      compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90,
      95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse
      events.5. Physical activity: (one study, 85 participants) based on short-term
      follow-up, a physical activity programme may cause a small reduction in
      prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69
      to -0.31, low QoE). We found no information regarding adverse events.6. Prostatic
      massage: (two studies, 115 participants) based on short-term follow-up, we are
      uncertain whether the prostatic massage reduces or increases prostatitis symptoms
      compared with control (very low QoE). We found no information regarding adverse
      events.7. Extracorporeal shockwave therapy: (three studies, 157 participants)
      based on short-term follow-up, extracorporeal shockwave therapy reduces
      prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46
      to -4.89, high QoE). These results may not be sustained at medium-term follow-up
      (low QoE). This treatment may not be associated with a greater incidence of
      adverse events (low QoE).8. Transrectal thermotherapy compared to medical
      therapy: (two studies, 237 participants) based on short-term follow-up,
      transrectal thermotherapy alone or in combination with medical therapy may
      decrease prostatitis symptoms slightly when compared with medical therapy alone
      (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study
      reported that participants may experience transient adverse events.9. Other
      interventions: there is uncertainty about the effects of other interventions
      included in this review. We found no information regarding psychological support
      or prostatic surgery. AUTHORS' CONCLUSIONS: Some of the interventions can
      decrease prostatitis symptoms in an appreciable number without a greater
      incidence of adverse events. The QoE was mostly low. Future clinical trials
      should include a full report of their methods including adequate masking,
      consistent assessment of all patient-important outcomes including potential
      treatment-related adverse events and appropriate sample sizes.

PMID- 29372566
TI  - Symptom association probability does not reliably distinguish functional
      heartburn from reflux hypersensitivity.
AB  - BACKGROUND: Symptom association probability (SAP) is thought to distinguish
      reflux hypersensitivity from functional disorders. A diagnosis of hypersensitive
      oesophagus (SAP-positive) indicates that gastro-oesophageal reflux disease (GERD)
      is the cause of continued symptoms. AIM: To conduct an analysis of pH and symptom
      criteria that lead to a diagnosis of SAP-positivity METHODS: We calculated SAP
      for 205 patients with GERD symptoms refractory to proton pump inhibitor (PPI)
      therapy who underwent endoscopy with wireless pH monitoring from 2007 to 2014.
      Patients were divided into three groups: pH-negative with no oesophagitis (n =
      45), pH-positive with no oesophagitis (n = 130), and patients with oesophagitis
      (n = 30). We constructed a 2 * 2 table of symptom and reflux event association
      and quantified the number of 2-minute intervals for each of the 2 * 2 variables
      that distinguished SAP-positive from SAP-negative. In a separate cohort of 58
      patients who had undergone anti-reflux surgery, we evaluated the effects of pre
      surgery SAP. RESULTS: The difference in symptom association parameters that led
      to a diagnosis of an SAP-positive was small (2.98% in oesophagitis-positive;
      1.56% in oesophagitis-negative/pH-positive; 0.48% in oesophagitis-negative/pH
      negative). In the pH-negative/oesophagitis-negative group, a difference of 0.48%
      led to a diagnosis of hypersensitivity. There was significant variability in SAP
      values between day 1 and day 2 of pH testing in all groups, with the greatest in
      the oesophagitis-positive group, despite objective evidence for reflux (27% in
      oesophagitis-positive, 19% pH-positive/oesophagitis-negative, and 7% in pH
      negative/oesophagitis-negative). Pre-surgery SAP was not associated with response
      to anti-reflux surgery. CONCLUSION: In PPI-refractory GERD, SAP cannot accurately
      distinguish reflux hypersensitivity from functional oesophageal symptoms.

PMID- 29372568
TI  - Multistage inhibitors of the malaria parasite: Emerging hope for chemoprotection
      and malaria eradication.
AB  - Over time, several exciting advances have been made in the treatment and
      prevention of malaria; however, this devastating disease continues to be a major
      global health problem and affects millions of people every year. Notably, the
      paucity of new efficient drug molecules and the inevitable drug resistance of the
      malaria parasite, Plasmodium falciparum, against frontline therapeutics are the
      foremost struggles facing malaria eradication initiatives. According to the
      malaria eradication agenda, the discovery of new chemical entities that can
      destroy the parasite at the liver stage, the asexual blood stage, the gametocyte
      stage, and the insect ookinete stage of the parasite life cycle (i.e., compounds
      exhibiting multistage activity) are in high demand, preferably with novel and
      multiple modes of action. Phenotypic screening of chemical libraries against the
      malaria parasite is certainly a crucial step toward overcoming these crises. In
      the last few years, various research groups, including industrial research
      laboratories, have performed large-scale phenotypic screenings that have
      identified a wealth of chemical entities active against multiple life stages of
      the malaria parasite. Vital scientific and technological developments have led to
      the discovery of multistage inhibitors of the malaria parasite; these compounds,
      considered highly valuable starting points for subsequent drug discovery and
      eradication of malaria, are reviewed.

PMID- 29372567
TI  - Review article: the physiological effects and safety of peppermint oil and its
      efficacy in irritable bowel syndrome and other functional disorders.
AB  - BACKGROUND: Peppermint oil has been used for centuries as a treatment for
      gastrointestinal ailments. It has been shown to have several effects on
      gastrointestinal physiology relevant to clinical care and management. AIM: To
      review the literature on peppermint oil regarding its metabolism, effects on
      gastrointestinal physiology, clinical use and efficacy, and safety. METHODS: We
      performed a PubMed literature search using the following terms individually or in
      combination: peppermint, peppermint oil, pharmacokinetics, menthol, oesophagus,
      stomach, small intestine, gallbladder, colon, transit, dyspepsia, nausea,
      abdominal pain, and irritable bowel syndrome. Full manuscripts evaluating
      peppermint oil that were published through 15 July 2017 were reviewed. When
      evaluating therapeutic indications, only randomised clinical trials were
      included. References from selected manuscripts were used if relevant. RESULTS: It
      appears that peppermint oil may have several mechanisms of action including:
      smooth muscle relaxation (via calcium channel blockade or direct enteric nervous
      system effects); visceral sensitivity modulation (via transient receptor
      potential cation channels); anti-microbial effects; anti-inflammatory activity;
      modulation of psychosocial distress. Peppermint oil has been found to affect
      oesophageal, gastric, small bowel, gall-bladder, and colonic physiology. It has
      been used to facilitate completion of colonoscopy and endoscopic retrograde
      cholangiopancreatography. Placebo controlled studies support its use in irritable
      bowel syndrome, functional dyspepsia, childhood functional abdominal pain, and
      post-operative nausea. Few adverse effects have been reported in peppermint oil
      trials. CONCLUSION: Peppermint oil is a natural product which affects physiology
      throughout the gastrointestinal tract, has been used successfully for several
      clinical disorders, and appears to have a good safety profile.

PMID- 29372569
TI  - Intravenous ketamine infusion for a patient with treatment-resistant major
      depression: a 10-month follow-up.
AB  - WHAT IS KNOWN AND OBJECTIVE: Ketamine in a subanaesthetic dose has been shown to
      produce rapid antidepressant effects. Here, we describe a long-term follow-up
      case of a Korean patient with severe major depression who received repeated
      ketamine intravenous therapy (KIT). CASE DESCRIPTION: A 49-year-old woman with a
      6-year history of treatment-resistant major depression was given KIT once every 1
      or 2 weeks over 10 months, for a total of 36 treatments. Her mood stabilized, and
      she showed a nearly 50% reduction in the severity of her depressive symptom. WHAT
      IS NEW AND CONCLUSION: Long-term repeated KIT may be an option for alleviating
      treatment-resistant and relapsing major depression. Further research and large
      clinical trials are needed on the optimum KIT protocol, including dose, dosing
      interval, total number of treatments and when to stop.

PMID- 29372570
TI  - Wnt is here! Could Wnt signalling be promoted to protect against Alzheimer
      disease?: An Editorial for 'Wnt signaling loss accelerates the appearance of
      neuropathological hallmarks of Alzheimer's disease in J20- APP transgenic and
      wild-type mice' on doi:10.1111/jnc.14278.
AB  - This Editorial highlights an article in the current issue by Tapia-Rojas and
      Inestrosa suggesting that attenuation of Wnt signalling may be a triggering
      factor for the pathogenesis of Alzheimer disease (AD) in the J20 mouse model of
      AD. Their study utilises Wnt signalling inhibitors that operate at different
      points in the signalling pathway. The molecular changes of several key Wnt
      signaling components are examined, along with a thorough analysis of both the
      amyloid and tau based pathologies in the mouse brain. Studies focusing on
      inhibition of Wnt signalling in AD mice have the potential to provide much needed
      information regarding the pathological mechanisms by which attenuated Wnt
      signalling impacts on AD.

PMID- 29372571
TI  - Snapshot-CEST: Optimizing spiral-centric-reordered gradient echo acquisition for
      fast and robust 3D CEST MRI at 9.4 T.
AB  - Gradient echo (GRE)-based acquisition provides a robust readout method for
      chemical exchange saturation transfer (CEST) at ultrahigh field (UHF). To develop
      a snapshot-CEST approach, the transient GRE signal and point spread function were
      investigated in detail, leading to optimized measurement parameters and
      reordering schemes for fast and robust volumetric CEST imaging. Simulation of the
      transient GRE signal was used to determine the optimal sequence parameters and
      the maximum feasible number of k-space lines. Point spread function analysis
      provided an insight into the induced k-space filtering and the performance of
      different rectangular reordering schemes in terms of blurring, signal-to-noise
      ratio (SNR) and relaxation dependence. Simulation results were confirmed in
      magnetic resonance imaging (MRI) measurements of healthy subjects. Minimal
      repetition time (TR) is beneficial for snapshot-GRE readout. At 9.4 T, for TR = 4
      ms and optimal flip angle close to the Ernst angle, a maximum of 562 k-space
      lines can be acquired after a single presaturation, providing decent SNR with
      high image quality. For spiral-centric reordered k-space acquisition, the image
      quality can be further improved using a rectangular spiral reordering scheme
      adjusted to the field of view. Application of the derived snapshot-CEST sequence
      for fast imaging acquisition in the human brain at 9.4 T shows excellent image
      quality in amide and nuclear Overhauser enhancement (NOE), and enables guanidyl
      CEST detection. The proposed snapshot-CEST establishes a fast and robust
      volumetric CEST approach ready for the imaging of known and novel exchange
      weighted contrasts at UHF.

PMID- 29372572
TI  - Intermolecular Desymmetrizing Gold-Catalyzed Yne-Yne Reaction of Push-Pull
      Diarylalkynes.
AB  - Push-pull diaryl alkynes are dimerized in the presence of a cationic gold
      catalyst. The polarized structure of the applied starting materials enables the
      generation of a highly reactive vinyl cation intermediate in an intermolecular
      reaction. Trapping of the vinyl cation by a nucleophilic attack of the electron
      poor aryl unit then leads to the selective formation of highly substituted
      naphthalenes in a single step and in complete atom economy.

PMID- 29372573
TI  - Endoscopic ultrasound for rectal cancer staging: A population-based study of
      utilization, impact on treatment patterns, and survival.
AB  - BACKGROUND AND AIM: Optimal rectal cancer (RC) outcomes depend on accurate
      locoregional staging. The study sought to describe the impact of endoscopic
      ultrasound (EUS) on RC treatment patterns and survival. METHODS: Using the
      Surveillance, Epidemiology, and End Results-Medicare database, the study
      identified patients with RC between 2005 and 2007. The study excluded patients
      with stage IV disease, those not enrolled in Medicare parts A and B, those
      enrolled in managed care, and those staged with pelvic magnetic resonance imaging
      (because of low numbers). The study then compared outcomes between patients who
      received EUS and computed tomography of the abdomen and pelvis (CTAP) to those
      staged with CTAP alone after propensity score matching. RESULTS: Between 2005 and
      2007, we identified 3,408 nonmetastatic RC patients. Compared with patients
      staged with CTAP alone, those who received EUS and CTAP were younger (median age:
      75 vs 76 years, P < 0.0001), more likely men (57.6% vs 48.7%, P < 0.0001), with a
      lower Charlson comorbidity index (P < 0.0001). Predictors of EUS included
      socioeconomic status (highest vs lowest) (odds ratio [OR] 1.87, 95% confidence
      interval [CI] 1.4-2.5), care by a gastroenterologist (OR 1.713, 95% CI 1.38
      2.13), and care in a teaching hospital (OR 1.68, 95% CI 1.35-2.08). Receipt of
      neoadjuvant chemoradiation was higher in EUS-staged patients (50.3% vs 16.0%, P <
      0.0001). EUS-staged patients had longer overall survival compared with those
      staged with CTAP alone (60 vs 57 months), but this was not statistically
      significant (P = 0.24). CONCLUSION: Endoscopic ultrasound in RC staging is
      associated with higher utilization of neoadjuvant chemoradiation without a
      significant difference in overall survival.

PMID- 29372574
TI  - Zero-Depth Interfacial Nanopore Capillaries.
AB  - High-fidelity analysis of translocating biomolecules through nanopores demands
      shortening the nanocapillary length to a minimal value. Existing nanopores and
      capillaries, however, inherit a finite length from the parent membranes. Here,
      nanocapillaries of zero depth are formed by dissolving two superimposed and
      crossing metallic nanorods, molded in polymeric slabs. In an electrolyte, the
      interface shared by the crossing fluidic channels is mathematically of zero
      thickness and defines the narrowest constriction in the stream of ions through
      the nanopore device. This novel architecture provides the possibility to design
      nanopore fluidic channels, particularly with a robust 3D architecture maintaining
      the ultimate zero thickness geometry independently of the thickness of the
      fluidic channels. With orders of magnitude reduced biomolecule translocation
      speed, and lowered electronic and ionic noise compared to nanopores in 2D
      materials, the findings establish interfacial nanopores as a scalable platform
      for realizing nanofluidic systems, capable of single-molecule detection.

PMID- 29372575
TI  - Distribution of Ebp pili among clinical and fecal isolates of Enterococcus
      faecalis and evaluation for human platelet activation.
AB  - Although Enterococcus faecalis is known as normal flora in colon, it is also
      amongst the most common causative agents of infective endocarditis (IE). Platelet
      activation resulting from adherence to platelets is an essential step in the
      pathogenesis of IE. One of the factors proposed in adhesion is endocarditis- and
      biofilm- associated pili encoded by ebp operon. The aim of this study was to
      investigate ebp in isolates from different origins and analyze the potential of
      isolates to activate human platelets of different donors. The ebp distribution
      was investigated in E. faecalis from different origin infections (n = 103) and
      fecal flora (n = 20). Then, selected isolates from blood (n = 5), urine (n = 2),
      and fecal flora (n = 3) were analyzed by flow cytometry assay for the ability to
      activate platelets of four different donors. No statistically significant
      difference was found for the ebp presence between infective and fecal isolates.
      Also, it was found that the ability for platelet activation is independent of the
      bacterial origin. However, significant difference was found in platelet
      activation between different donors. The results suggest that the presence or
      absence of ebp is not a critical factor for platelet activation by E. faecalis
      isolates. However, host factors seem to contribute in this activity.

PMID- 29372577
TI  - The association of interferon-gamma, interleukin-4 and interleukin-17 single
      nucleotide polymorphisms with susceptibility to tuberculosis.
AB  - Susceptibility to tuberculosis and progression of the disease depend on
      interactions between the bacterial agent, host immune system, and environmental
      and genetic factors. In this case-controlled study, we aimed to determine the
      role of single-nucleotide polymorphisms of interferon-gamma, interleukin-4 and
      interleukin-17 in susceptibility to tuberculosis. Genomic DNA was extracted from
      peripheral blood samples of patients and controls. The association of single
      nucleotide polymorphisms in interleukin-4 (-590C/T), interleukin-17 (-152A/G) and
      interferon-gamma (+874T/A) was investigated by polymerase chain reaction (PCR)
      restriction fragment length polymorphism and amplification refractory mutation
      system-PCR. A total of 76 tuberculosis patients and 119 healthy individuals were
      included in this study. The interferon-gamma (+874T/A) TA genotype was
      significantly associated with susceptibility to tuberculosis in patients compared
      to controls (OR = 1.76; 95%CI = 0.84-3.71; p = 0.007), while the interferon-gamma
      (+874T/A) TT genotype (OR = 0.51; 95%CI = 0.19-1.36; p = 0.007) had protective
      effects against tuberculosis and was related to a low risk of tuberculosis
      development. The difference between allelic and genotypic frequencies of
      interleukin-4 (-590C/T) between patients and controls was not significant (p =
      0.46). Multivariate logistic regression analysis revealed that the interleukin-17
      (-152A/G) AG genotype (OR = 2.27; 95%CI = 1.19-4.34; p = 0.03) and AA genotype
      (OR = 1.03; 95%CI = 0.43-2.44; p = 0.03) were significantly different between
      patients and controls. In conclusion, single-nucleotide mutations in different
      cytokine genes may have protective effects or increase the risk of tuberculosis.

PMID- 29372576
TI  - Long-term outcomes of rotational atherectomy of underexpanded stents. A single
      center experience.
AB  - OBJECTIVES: To analyze the procedural and long-term outcomes of the use of
      rotational atherectomy (RA) in underexpanded stents in our cohort and to provide
      an overview of currently available data on this technique. BACKGROUND: Stent
      underexpansion (SU) has been related to stent thrombosis and restenosis. RA has
      been used to treat undilatable SU as a bail-out strategy with encouraging
      results. METHODS: This is an observational, single-center study. We included
      patients who underwent stentablation between 2013 and 2017. Baseline
      demographics, procedural results, in-hospital major adverse cardiac events
      (MACE), and long-term follow-up MACE were retrospectively collected. RESULTS: A
      total of 11 patients (90.9% males, mean age 65.4 +/- 18.6) were included in this
      study. Median left ventricle ejection fraction was 53.5% [46.2-55]. Median
      calculated Syntax score was 16 [9-31] and 45.5% of patients were admitted for
      acute coronary syndrome. Radial approach was used in 63.6% of cases. Most
      patients only required one burr (45% used a 1.5 mm diameter burr) during the
      intervention. Procedural success was achieved in 90.9% of the cases. Acute lumen
      gain was 42.7% [30.7-61.49]. There were no in-hospital deaths or MACE. At a
      median follow-up of 26 months, only one patient (9.1%) suffered MACE in the
      context of acute coronary syndrome, and two patients (18.2%) required non-target
      lesion revascularization. No deaths were reported. CONCLUSIONS: RA of under
      expanded stents is a feasible option with a high rate of procedural success. At
      long-term follow-up, all of them were alive and 90.9% of patients remained free
      from MACE.

PMID- 29372579
TI  - Exceeding the daily dosing limit of nonsteroidal anti-inflammatory drugs among
      ibuprofen users.
AB  - PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective and very
      commonly used, but also have side effects. We determined prevalence of NSAID
      dosing exceeding the daily limit (EDL) and identified related user
      characteristics and dosing patterns among current ibuprofen users. METHODS:
      Online 1-week diary study of 1326 ibuprofen users. NSAIDs were identified by list
      based prompting; respondents were not required to know their medications were
      NSAIDs. Details of hourly use were recorded by respondents daily. Deviations from
      dosing directions were programmatically determined afterwards. An exit survey
      obtained information on demographics, medical history, physical and mental health
      status, attitudes regarding label reading and dosing behavior, and knowledge of
      product label instructions. RESULTS: Most diary users (90%) took over-the-counter
      ibuprofen during the week; 37% also took non-ibuprofen NSAIDs. Most did not
      recognize all products taken as NSAIDs. EDL occurred among 11% of users for
      ibuprofen, 4% of users for other NSAIDs, and on 9.1% of NSAID usage days. EDL was
      associated with deviations from detailed dosing directions, particularly
      exceeding the 1-time dose, which occurred more often with medications with 1-pill
      doses. Personal characteristics associated with EDL included male sex, ongoing
      pain, poor physical function, daily smoking, having the attitudes of "choosing my
      own dose" and not starting with the lowest dose, and poor knowledge of the
      recommended 1-time and 24-hour doses. CONCLUSIONS: The prevalence of EDL among
      NSAID users is nontrivial, and it is associated with potentially modifiable
      factors. Educating consumers about NSAIDs and their dosing directions could
      reduce excess dosing.

PMID- 29372578
TI  - Ultrasound guidance versus anatomical landmark approach for femoral artery access
      in coronary angiography: A randomized controlled trial and a meta-analysis.
AB  - OBJECTIVES: The objective was to assess the effect of ultrasound (US)-guidance
      compared to the anatomical landmark (AL) approach in patients requiring femoral
      artery (FA) access for coronary angiography/percutaneous coronary interventions
      (PCI). BACKGROUND: US-guidance has been proposed as a strategy to optimize FA
      access, potentially leading to decreased vascular complications. METHODS:
      Patients requiring FA access for coronary angiography/PCI were randomized to the
      US-guided or AL approaches. The primary endpoint was a composite of immediate
      procedural vascular outcomes, and access-site outcomes at day one. Results were
      subsequently pooled in a study-level meta-analysis of randomized trials comparing
      US-guided FA access to another strategy. RESULTS: A total of 129 patients were
      randomized (64 US-guided group; 65 AL group). The primary endpoint occurred in 30
      patients (47%) with US, and in 39 patients (62%) with AL (P = 0.09). Four
      additional studies met the inclusion criteria and were included in the meta
      analysis (1553 patients). Following data pooling, bleeding events (OR = 0.41;
      95%CI 0.20-0.83; P = 0.01), venipunctures (OR = 0.18; 95%CI: 0.11-0.29; P <
      0.0001), and multiple puncture attempts (OR = 0.24; 95%CI: 0.19-0.31; P < 0.0001)
      were significantly improved with US-guidance, but not successful common FA
      cannulation (OR = 0.84; 95%CI: 0.60-1.17; P = 0.29). CONCLUSION: Our study did
      not show significant benefits for the use of US to guide arterial femoral access
      compared to the anatomical landmark approach, but pooled analysis of five
      randomized trials showed decreased rates of bleeding events and venipunctures,
      and improved first-pass success. The clinical impact of these findings is
      uncertain, and do not warrant a systematic use of US-guidance in this clinical
      setting.

PMID- 29372580
TI  - Young children's non-numerical ordering ability at the start of formal education
      longitudinally predicts their symbolic number skills and academic achievement in
      maths.
AB  - Ordinality is a fundamental feature of numbers and recent studies have
      highlighted the role that number ordering abilities play in mathematical
      development (e.g., Lyons et al., ), as well as mature mathematical performance
      (e.g., Lyons & Beilock, ). The current study tested the novel hypothesis that non
      numerical ordering ability, as measured by the ordering of familiar sequences of
      events, also plays an important role in maths development. Ninety children were
      tested in their first school year and 87 were followed up at the end of their
      second school year, to test the hypothesis that ordinal processing, including the
      ordering of non-numerical materials, would be related to their maths skills both
      cross-sectionally and longitudinally. The results confirmed this hypothesis.
      Ordinal processing measures were significantly related to maths both cross
      sectionally and longitudinally, and children's non-numerical ordering ability in
      their first year of school (as measured by order judgements for everyday events
      and the parents' report of their child's everyday ordering ability) was the
      strongest longitudinal predictor of maths one year later, when compared to
      several measures that are traditionally considered to be important predictors of
      early maths development. Children's everyday ordering ability, as reported by
      parents, also significantly predicted growth in formal maths ability between Year
      1 and Year 2, although this was not the case for the event ordering task. The
      present study provides strong evidence that domain-general ordering abilities
      play an important role in the development of children's maths skills at the
      beginning of formal education.

PMID- 29372581
TI  - Functional Hydride Transfer by a Thiolate-Containing Model of Mono-Iron
      Hydrogenase featuring an Anthracene Scaffold.
AB  - We report the synthesis, X-ray structure and functional biomimetic activity of a
      model complex of mono-iron hydrogenase (Hmd). To achieve the desired biomimetic
      fac-CNS(thiolate) ligation motif, an anthracene framework is used to provide the
      requisite donors in a single chelate. A bulky aryl thiolate (ortho
      dimethylphenyl) is included to achieve mononuclearity. In addition to exhibiting
      structural (X-ray) and spectroscopic (NMR, IR) similarity to the enzyme, the
      complex is competent for H2 activation (heterolysis) and hydride transfer to a
      model substrate-mimicking the functional behavior of the enzyme in a biomimetic
      CNS coordination sphere for the first time.

PMID- 29372582
TI  - Bayesian dose-finding phase I trial design incorporating historical data from a
      preceding trial.
AB  - We consider the problem of incorporating historical data from a preceding trial
      to design and conduct a subsequent dose-finding trial in a possibly different
      population of patients. In oncology, for example, after a phase I dose-finding
      trial is completed in Caucasian patients, investigators often conduct a further
      phase I trial to determine the maximum tolerated dose in Asian patients. This may
      be due to concerns about possible differences in treatment tolerability between
      populations. In this study, we propose to adaptively incorporate historical data
      into prior distributions assumed in a new dose-finding trial. Our proposed
      approach aims to appropriately borrow strength from a previous trial to improve
      the maximum tolerated dose determination in another patient population. We define
      a "historical-to-current (H-C)" parameter representing the degree of borrowing
      based on a retrospective analysis of previous trial data. In simulation studies,
      we examine the operating characteristics of the proposed method in comparison
      with 3 alternative approaches and assess how the H-C parameter functions across a
      variety of realistic settings.

PMID- 29372583
TI  - Transparent, Flexible, Conformal Capacitive Pressure Sensors with Nanoparticles.
AB  - The fundamental challenge in designing transparent pressure sensors is the ideal
      combination of high optical transparency and high pressure sensitivity.
      Satisfying these competing demands is commonly achieved by a compromise between
      the transparency and usage of a patterned dielectric surface, which increases
      pressure sensitivity, but decreases transparency. Herein, a design strategy for
      fabricating high-transparency and high-sensitivity capacitive pressure sensors is
      proposed, which relies on the multiple states of nanoparticle dispersity
      resulting in enhanced surface roughness and light transmittance. We utilize two
      nanoparticle dispersion states on a surface: (i) homogeneous dispersion, where
      each nanoparticle (~500 nm) with a size comparable to the visible light
      wavelength has low light scattering; and (ii) heterogeneous dispersion, where
      aggregated nanoparticles form a micrometer-sized feature, increasing pressure
      sensitivity. This approach is experimentally verified using a nanoparticle
      dispersed polymer composite, which has high pressure sensitivity (1.0 kPa-1 ),
      and demonstrates excellent transparency (>95%). We demonstrate that the
      integration of nanoparticle-dispersed capacitor elements into an array readily
      yields a real-time pressure monitoring application and a fully functional touch
      device capable of acting as a pressure sensor-based input device, thereby opening
      up new avenues to establish processing techniques that are effective on the
      nanoscale yet applicable to macroscopic processing.

PMID- 29372584
TI  - Evolving doublesex expression correlates with the origin and diversification of
      male sexual ornaments in the Drosophila immigrans species group.
AB  - Male ornaments and other sex-specific traits present some of the most dramatic
      examples of evolutionary innovations. Comparative studies of similar but
      independently evolved traits are particularly important for identifying repeated
      patterns in the evolution of these traits. Male-specific modifications of the
      front legs have evolved repeatedly in Drosophilidae and other Diptera. The best
      understood of these novel structures is the sex comb of Drosophila melanogaster
      and its close relatives. Here, we examine the evolution of another male foreleg
      modification, the sex brush, found in the distantly related Drosophila immigrans
      species group. Similar to the sex comb, we find that the origin of the sex brush
      correlates with novel, spatially restricted expression of the doublesex (dsx)
      transcription factor, the primary effector of the Drosophila sex determination
      pathway. The diversity of Dsx expression patterns in the immigrans species group
      closely reflects the differences in the presence, position, and size of the sex
      brush. Together with previous work on sex comb evolution, these observations
      suggest that tissue-specific activation of dsx expression may be a common
      mechanism responsible for the evolution of sexual dimorphism and particularly for
      the origin of novel male-specific ornaments.

PMID- 29372585
TI  - Life-Space Assessment questionnaire: Novel measurement properties for Brazilian
      community-dwelling older adults.
AB  - AIM: The Life-Space Assessment (LSA) assesses mobility from the spaces that older
      adults go, and how often and how independent they move. Despite its increased
      use, LSA measurement properties remain unclear. The aim of the present study was
      to analyze the content validity, reliability, construct validity and
      interpretability of the LSA for Brazilian community-dwelling older adults.
      METHODS: In this clinimetric study we analyzed the measurement properties
      (content validity, reliability, construct validity and interpretability) of the
      LSA administered to 80 Brazilian community-dwelling older adults. Reliability was
      analyzed by Cronbach's alpha (internal consistency), intraclass correlation
      coefficients and 95% confidence interval (reproducibility), and standard error of
      measurement (measurement error). Construct validity was analyzed by Pearson's
      correlations between the LSA and accelerometry (time in inactivity and moderate
      to-vigorous activities), and interpretability was analyzed by determination of
      the minimal detectable change, and floor and ceiling effects. RESULTS: The LSA
      met the criteria for content validity. The Cronbach's alpha was 0.92, intraclass
      correlation coefficient was 0.97 (95% confidence interval 0.95-0.98) and standard
      error of measurement was 4.12. The LSA showed convergence with accelerometry
      (negative correlation with time in inactivity and positive correlation with time
      in moderate to vigorous activities), the minimal detectable change was 0.36 and
      we observed no floor or ceiling effects. CONCLUSIONS: The LSA showed adequate
      reliability, validity and interpretability for life-space mobility assessment of
      Brazilian community-dwelling older adults. Geriatr Gerontol Int 2018; 18: 783
      789.

PMID- 29372586
TI  - Risk of psychological distress in partners with functional disability among older
      Japanese adults.
AB  - AIM: The present cross-sectional study aimed to evaluate the association of
      psychological distress with a partner's disability in an older Japanese
      population, as well as the effect modification of social support on this
      association. METHODS: The baseline survey was carried out between 1 December and
      15 December 2006, and included 6809 participants from whom we collected data
      regarding functional disability and psychological distress. We defined functional
      disability as certification for long-term care insurance in Japan, and
      psychological distress as a Kessler 6 score of >=10 out of 24. A multiple
      logistic regression analysis was used to calculate odds ratios (OR) and 95%
      confidence intervals (CI) for increased psychological distress according to the
      categories of functional disability among partners. Stratified analyses were also
      carried out to investigate whether social support significantly affected the
      association between a partner's functional disability and psychological distress.
      RESULTS: The multiple-adjusted OR for psychological distress was 1.48 (95% CI
      1.06-2.04) among participants whose partners had functional disabilities (vs
      those whose partners did not have functional disabilities). In the social support
      stratified analysis, a significant association with psychological distress was
      observed among participants lacking social support for help with their daily
      housework (OR 2.47, 95% CI 1.23-4.83), but not among those with social support
      (OR 1.18, 95% CI 0.79-1.72); P for interaction = 0.03). CONCLUSIONS: A partner
      with functional disability conferred a significantly higher risk of psychological
      distress on older Japanese individuals, and this association was modified by
      social support. We conclude that social support might buffer psychological
      distress in this population. Geriatr Gerontol Int 2018; 18: 775-782.

PMID- 29372587
TI  - Psychosocial impact of Parkinson's disease-associated dysarthria: Cross-cultural
      adaptation and validation of the Dysarthria Impact Profile into European
      Portuguese.
AB  - AIM: The present study sought to make a cross-cultural adaptation of the
      Dysarthria Impact Profile (DIP) for European Portuguese (EP) and validate it for
      use in Parkinson's disease (PD) patients. METHODS: The cross-cultural adaptation
      was carried out in accordance with the guidelines. The EP version of the DIP was
      administered to 80 people with PD, and 30 sex- and age-matched control
      participants. Psychometric properties, acceptability, feasibility reliability
      (internal consistency and intrarater agreement) and validity (construct,
      convergent and known-groups validity) were assessed using other assessment tools
      (motor disability and impairment, and voice impact). RESULTS: Overall, the EP-DIP
      final version has the same conceptual meaning, semantics, idiomatic and score
      equivalences as the original version. Statistical analyses showed adequate
      feasibility (missing data <5%), good acceptability (ceiling or floor effects
      <15%; high requests of assistance to complete the questionnaire), satisfactory
      internal consistency (Cronbach's alpha = 0.9), weak-to-moderate intrarater
      reliability, good construct validity, strong convergent validity (with the Voice
      Handicap Index; Spearman's P = -0.8) and good known-groups validity (between
      those with PD and control participants). CONCLUSIONS: The EP-DIP version displays
      the salient features of a valid patient-based assessment tool used to measure the
      psychosocial impact of slight-to-mild dysarthria in people with PD. Geriatr
      Gerontol Int 2018; 18: 767-774.

PMID- 29372588
TI  - Five decades of the Fontan operation: A systematic review of international
      reports on outcomes after univentricular palliation.
AB  - Almost fifty years after its first clinical application, the modified Fontan
      operation is among the most frequently performed procedures in congenital heart
      disease surgery in children today. The objective of this review is to
      systematically summarize the international evolution of outcomes in regard to
      morbidity and mortality of patients with Fontan palliation. All studies published
      over the past five decades with more than 100 Fontan patients included were
      screened. In eligible studies, information concerning preoperative patients'
      characteristics, Fontan modifications employed, early mortality, long-term
      survival and frequency of relevant complications was extracted. Ultimately,
      thirty-one studies published by the largest surgical centers with an overall
      number of 9390 patients were included in this review. The extracardiac total
      cavopulmonary anastomosis is the most frequently used Fontan modification.
      Hemodynamic data demonstrate a rigorous overall adherence to suggested Fontan
      selection criteria. The analysis showed a clear trend toward improved early and
      long-term survival over the time period covered. Although inconsistently
      reported, severe complications such as arrhythmias, thromboembolic events and
      protein-losing enteropathy as well as reoperations and reinterventions were
      frequent. In conclusion, patients palliated for complex univentricular heart
      malformations nowadays benefit from the experience and technical developments of
      the past decades and have a significantly improved long-term prognosis. However,
      important issues concerning postoperative long-term morbidity and mortality are
      still unsolved and clear intrinsic limitations of the Fontan circulation are
      becoming evident as the population of Fontan patients ages.

PMID- 29372589
TI  - Aerobic exercise in depressed youth: A feasibility and clinical outcomes pilot.
AB  - AIM: Major depressive disorder (MDD) onset generally occurs in adolescence/early
      adulthood. However, pharmacotherapy use in younger populations is restricted due
      to black box warnings. Aerobic exercise may be a viable treatment option for mild
      to-moderate MDD, but little is known about its acceptability/effectiveness in
      young adults. METHODS: Unmedicated and relatively inactive 18-to-24 olds with MDD
      completed fitness/clinical assessments at baseline and after 12 weeks of
      supervised aerobic exercise (3*/wk; 30-minute sessions in target heart rate [HR]
      zone), with the aim of increasing cardiovascular fitness (VO2max -indexed).
      RESULTS: Post-intervention, predicted VO2max increased, whereas depression scores
      decreased. A correlation existed between time spent in target HR zone and anxiety
      symptom decreases. Exercise adherence and satisfaction were high, and drop-out
      was minimal. CONCLUSIONS: This pilot is among the first to assess the feasibility
      of aerobic exercise as an antidepressant treatment strategy in young adults, a
      group for which options have limited acceptability.

PMID- 29372590
TI  - A Comparative Analysis of Attitudes on Communication Toward Stem Cell Research
      and Regenerative Medicine Between the Public and the Scientific Community.
AB  - Owing to the rapid progress in stem cell research (SCR) and regenerative medicine
      (RM), society's expectation and interest in these fields are increasing. For
      effective communication on issues concerning SCR and RM, surveys for
      understanding the interests of stakeholders is essential. For this purpose, we
      conducted a large-scale survey with 2,160 public responses and 1,115 responses
      from the member of the Japanese Society for Regenerative Medicine. Results showed
      that the public is more interested in the post-realization aspects of RM, such as
      cost of care, countermeasures for risks and accidents, and clarification of
      responsibility and liability, than in the scientific aspects; the latter is of
      greater interest only to scientists. Our data indicate that an increased
      awareness about RM-associated social responsibility and regulatory framework is
      required among scientists, such as those regarding its benefits, potential
      accidents, abuse, and other social consequences. Awareness regarding the
      importance of communication and education for scientists are critical to bridge
      the gaps in the interests of the public and scientists. Stem Cells Translational
      Medicine 2018;7:251-257.

PMID- 29372591
TI  - Clinical yield of fetal echocardiography for suboptimal cardiac visualization on
      obstetric ultrasound.
AB  - OBJECTIVE: Suboptimal cardiac imaging on obstetric ultrasound is a frequent
      referral indication for fetal echocardiography, even in the absence of typical
      risk factors for fetal cardiac disease. The clinical profile of patients and
      findings of examinations performed for such an indication are not well defined.
      Given the increased cost, time and resource utilization of fetal
      echocardiography, we sought to determine the clinical findings of such referrals.
      STUDY DESIGN: We performed a single-center review of such referrals from January
      2010 to June 2016. Patients with commonly accepted indications for fetal
      echocardiography were excluded. Demographic variables and echocardiogram findings
      were collected. Findings were classified as (1) "normal," (2) "probably normal,"
      if minor pathology could not confidently be excluded, or if minor findings were
      noted that were expected to resolve, or (3) "abnormal." Rates of pathology were
      determined with comparison of nonobese and obese populations. RESULTS: A total of
      583 gestations in 562 women were included (median gestational age 23.3 weeks,
      range 19.0-38.4). The median body mass index (BMI) was 34.6 kg/m2 (range 17.2
      66.3 kg/m2 ). The majority of women were obese (BMI >= 30 kg/m2 in 74.6%).
      Overall, 574 of 583 examinations (98.5%) were normal or "probably normal."
      Pathology was noted in 9 fetuses (1.5%), 3 of whom required intervention (0.5%).
      No ductal dependent lesions were diagnosed. There was no significant difference
      in pathology rates between nonobese and obese mothers. CONCLUSIONS: We found a
      low fetal cardiac anomaly rate in studies performed for suboptimal views on
      obstetric ultrasound. The majority of women referred for this indication were
      obese. The practice of routine referral for this indication deserves further
      evaluation.

PMID- 29372592
TI  - Rasagiline delays retinal degeneration in a mouse model of retinitis pigmentosa
      via modulation of Bax/Bcl-2 expression.
AB  - AIMS: Retinitis pigmentosa (RP) is an inherited disease characterized by a
      progressive degeneration of rod photoreceptors. An imbalance between pro- and
      antiapoptotic factors, such as Bax/Bcl-2, has been involved in retinal
      degeneration. To date, no cure or effective treatments are available for RP.
      Rasagiline is an antiparkinsonian drug that has shown neuroprotective effects in
      part attributed to a modulation of Bax/Bcl-2 expression. In this study, we have
      evaluated the use of rasagiline as a potential treatment for RP. METHODS: Newborn
      rd10 mice, a RP model, were treated with oral rasagiline during 30 days followed
      by a functional and morphological characterization of their mouse retinas.
      RESULTS: Treated animals showed a significant improvement in visual acuity and in
      the electrical responses of photoreceptors to light stimuli. Rasagiline delayed
      photoreceptor degeneration, which was confirmed not only by a high photoreceptor
      nuclei counting, but also by a sustained expression of photoreceptor-specific
      markers. In addition, the expression of proapoptotic Bax decreased, whereas the
      antiapoptotic factor Bcl-2 increased after rasagiline treatment. CONCLUSION: This
      study provides new evidences regarding the neuroprotective effect of rasagiline
      in the retina, and it brings new insight into the development of future clinical
      trials using this well-established antiparkinsonian drug to treat RP.

PMID- 29372593
TI  - Lipoedema in patients after bariatric surgery: report of two cases and review of
      literature.
AB  - Lipoedema is a disorder of adipose tissue that is characterized by abnormal
      subcutaneous fat deposition, leading to swelling and enlargement of the lower
      limbs as well as the trunk. This entity is often misdiagnosed as lymphoedema or
      obesity and, therefore, may be overlooked and missed in patients scheduled for
      bariatric surgery. Patients with lipoedema who undergo bariatric surgery may have
      to continue to have extensive lower extremity and trunk adiposity despite
      adequate weight loss. In this report, we present two patients who had extensive
      trunk and lower extremity adiposity, one of them before and the other after the
      bariatric surgery.

PMID- 29372594
TI  - Development and validation of a clinically applicable score to classify cachexia
      stages in advanced cancer patients.
AB  - BACKGROUND: Cachexia is a multifactorial syndrome that is highly prevalent in
      advanced cancer patients and leads to progressive functional impairments. The
      classification of cachexia stages is essential for diagnosing and treating
      cachexia. However, there is a lack of simple tools with good discrimination for
      classifying cachexia stages. Therefore, our study aimed to develop a clinically
      applicable cachexia staging score (CSS) and validate its discrimination of
      clinical outcomes for different cachexia stages. METHODS: Advanced cancer
      patients were enrolled in our study. A CSS comprising the following five
      components was developed: weight loss, a simple questionnaire of sarcopenia (SARC
      F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry.
      According to the CSS, patients were classified into non-cachexia, pre-cachexia,
      cachexia, and refractory cachexia stages, and clinical outcomes were compared
      among the four groups. RESULTS: Of the 297 participating patients, data from 259
      patients were ultimately included. Based on the CSS, patients were classified
      into non-cachexia (n = 69), pre-cachexia (n = 68), cachexia (n = 103), and
      refractory cachexia (n = 19) stages. Patients with more severe cachexia stages
      had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female
      patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027
      in male and female patients, respectively), more severe symptom burden (P <
      0.001), poorer quality of life (P < 0.001 for all subscales except social well
      being), and shorter survival times (P < 0.001). CONCLUSIONS: The CSS is a simple
      and clinically applicable tool with excellent discrimination for classifying
      cachexia stages. This score is extremely useful for the clinical treatment and
      prognosis of cachexia and for designing clinical trials.

PMID- 29372595
TI  - Methotrexate might reduce ischemic stroke in patients with rheumatoid arthritis:
      a population-based retrospective cohort study.
AB  - AIM: To investigate the effects of hydroxychloroquine, sulfasalazine and
      methotrexate on ischemic stroke in patients with rheumatoid arthritis (RA).
      METHODS: This population-based retrospective cohort study included 7904 RA
      patients and 15 808 non-RA patients between 2000 and 2010. All of the
      participants were sampled from the National Health Insurance Research Database
      (NHIRD) of Taiwan. Using univariate analyses, these two groups of patients were
      compared to evaluate the differences in disease-modifying anti-rheumatic drugs
      usage and demographic variables. Cox proportional hazard models and Schoenfeld
      residuals test were performed to estimate the hazard ratios for ischemic stroke
      and proportional hazard assumptions of these drugs, respectively. RESULTS: The
      mean age of participants was about 53 years old, and about 70% of RA patients
      were women. The hazard ratio for ischemic stroke was 1.21 (95% CI: 1.10-1.34; P <
      0.01) in the case group compared with the control group, and this significant
      difference persisted throughout the 10-year period. With respect to RA patients,
      while hydroxychloroquine showed an insignificant protective effect on ischemic
      stroke, sulfasalazine and methotrexate were found out to have inconsistent
      effects during these 10 years. The proportional hazard assumption test of
      methotrexate at > 0.5 defined daily dose (8.75 mg/week) was violated at a
      significant level after adjustment (P = 0.0002). CONCLUSIONS: At a dosage of >
      0.5 defined daily dose, short-term methotrexate might decrease ischemic stroke
      risk in RA patients, while hydroxychloroquine and sulfasalazine were neutral.

PMID- 29372596
TI  - Histopathological evaluation of duodenal biopsy in the PreventCD project. An
      observational interobserver agreement study.
AB  - Aim of the current study was to evaluate the inter-observer agreement between
      pathologists in the diagnosis of celiac disease (CD), in the qualified context of
      a multicenter study. Biopsies from the "PreventCD" study, a multinational-
      prospective- randomized study in children with at least one-first-degree relative
      with CD and positive for HLA-DQ2/HLA-DQ8. Ninety-eight biopsies were evaluated.
      Considering diagnostic samples with villous atrophy (VA), the agreement was
      satisfactory (kappa = 0.84), but much less when assessing the severity of these
      lesions. The use of the recently proposed Corazza-Villanacci classification
      showed a moderately higher level of agreement (kappa = 0.39) than using the Marsh
      Oberhuber system (kappa = 0.31). 57.1% of cases were considered correctly
      oriented. A number of >4 samples per patient was statistically associated to a
      better agreement; orientation did not impact on kappa values. Agreement results
      in this study appear more satisfactory than in previous papers and this is
      justified by the involvement of centers with experience in CD diagnosis and by
      the well-controlled setting. Despite this, the reproducibility was far from
      optimal with a poor agreement in grading the severity of VA. Our results stress
      the need of a minimum of four samples to be assessed by the pathologist.

PMID- 29372597
TI  - Differences in the neural correlates of frontal lobe tests.
AB  - BACKGROUND: The Executive Interview (EXIT25), the executive clock-drawing task
      (CLOX1), and the Frontal Assessment Battery (FAB) are used to assess executive
      function at the bedside. These tests assess distinct psychometric properties. The
      aim of this study was to examine differences in the neural correlates of the
      EXIT25, CLOX1, and FAB based on magnetic resonance imaging. METHODS: Fifty-eight
      subjects (30 with Alzheimer's disease, 10 with mild cognitive impairment, and 18
      healthy controls) participated in this study. Multiple regression analyses were
      performed to examine the brain regions correlated with the EXIT25, CLOX1, and FAB
      scores. Age, gender, and years of education were included as covariates.
      Statistical thresholds were set to uncorrected P-values of 0.001 at the voxel
      level and 0.05 at the cluster level. RESULTS: The EXIT25 score correlated
      inversely with the regional grey matter volume in the left lateral frontal lobe
      (Brodmann areas 6, 9, 44, and 45). The CLOX1 score correlated positively with the
      regional grey matter volume in the right orbitofrontal cortex (Brodmann area 11)
      and the left supramarginal gyrus (Brodmann area 40). The FAB score correlated
      positively with the regional grey matter volume in the right precentral gyrus
      (Brodmann area 6). The left lateral frontal lobe (Brodmann area 9) and the right
      lateral frontal lobe (Brodmann area 46) were identified as common brain regions
      that showed association with EXIT25, CLOX1, and FAB based only a voxel-level
      threshold. CONCLUSIONS: The results of this study suggest that the EXIT25, CLOX1,
      and FAB may be associated with the distinct neural correlates of the frontal
      cortex.

PMID- 29372598
TI  - Risk of hospitalization associated with anticholinergic medication for patients
      with dementia.
AB  - BACKGROUND: With the ageing of the general population, demand has grown for
      measures to prevent hospitalization for dementia, which can exacerbate problems
      associated with activities of daily living in elderly individuals.
      Anticholinergic medication has been shown to cause falls, delirium, and cognitive
      impairment in aged patients. However, the risk of hospitalization associated with
      the administration of anticholinergics is unclear. METHODS: We analyzed the
      records of 61 outpatients (26 men, 35 women; mean age: 78 +/- 7 years; mean
      follow-up period: 420 days) diagnosed with dementia (Alzheimer's disease: n = 45;
      dementia with Lewy bodies: n = 3; undifferentiated n = 13) and prescribed anti
      dementia drugs between May 2013 and December 2014. Medication history was noted,
      and the patients were divided into two groups according to the Anticholinergic
      Risk Scale: with risk (n = 13) and without risk (n = 48). Outcome was judged
      based on an end-point of hospitalization or death. Kaplan-Meier survival and Cox
      proportional hazard analyses were performed. RESULTS: Eight patients with
      anticholinergic risk and 12 without anticholinergic risk reached the end-point (P
      < 0.005). Analysis with a proportional hazard model showed that anticholinergic
      medication administration was related to a higher risk for reaching the end-point
      (crude hazard ratio: 3.62, 95% confidence interval: 1.45-9.04, P < 0.01; adjusted
      hazard ratio: 4.54, 95% confidence interval: 1.03-20.0, P < 0.05). In contrast,
      Mini-Mental State Examination score, Charlson Comorbidity Index, and the number
      of drugs were not major risk factors for hospitalization in patients with
      dementia. CONCLUSION: The Anticholinergic Risk Scale findings were shown to be a
      strong predictor of hospitalization for patients with dementia. We should
      evaluate the anticholinergic burden before initiating anti-dementia therapy.

PMID- 29372599
TI  - Clinical significance of cognitive rehabilitation and psychoeducational
      intervention for family caregivers of patients with posterior cortical atrophy: a
      longitudinal study.

PMID- 29372600
TI  - Effect of preceding home-visit nursing on time to discharge in hospitalization
      for the treatment of behavioural and psychological symptoms of dementia among
      patients with limited familial care.
AB  - BACKGROUND: During hospitalization for behavioural and psychological symptoms of
      dementia (BPSD), it is imperative to build a support system for each patient in
      the community for after they obtain symptom remission. To this end, patients
      lacking adequate family support are less likely to be discharged to their own
      homes and need stronger support systems to be established. This study therefore
      investigated the effects of home-visit nursing before admission on time to home
      discharge among patients with limited familial care who were hospitalized for
      treatment of BPSD. METHODS: A single-centre chart review study was conducted on
      consecutive patients admitted from home between April 2013 and September 2015 for
      treatment of BPSD and who had lived alone or with a working family member. Time
      to home discharge was compared between patients who had home-visit nursing before
      their admission and those who did not. RESULTS: In total, 58 patients were
      enrolled in the study, of whom 12 had preceding home-visit nursing (PHN group)
      and 46 did not (non-PHN group). Patients in the PHN group were younger (77.7 +/-
      4.9 vs. 84.1 +/- 6.1 years, P = 0.0011) and had higher Mini-Mental State
      Examination scores (16.8 +/- 7.2 vs 11.8 +/- 7.3, P = 0.0287). A multivariate Cox
      proportional hazard regression analysis adjusted for age and Mini-Mental State
      Examination scores showed a higher likelihood of discharge to home in the PHN
      group (hazard ratio: 3.85; 95% confidence interval: 1.27-11.6;, P = 0.017) than
      in the non-PHN group. CONCLUSION: Home-visit nursing before admission of BPSD
      patients for treatment could improve the rate of discharge to home among patients
      with limited familial care after subsequent hospitalization. Home-visit nursing
      could also enhance collaborative relationships between social and hospital-based
      care systems, and early implementation could improve the likelihood of vulnerable
      patient types remaining in their own homes for as long as possible.

PMID- 29372601
TI  - Comparing the neuropsychological profiles of mild dementia with Lewy bodies and
      mild Alzheimer's disease.
AB  - BACKGROUND: The present study was conducted to detect neuropsychological
      differences and to identify discriminators between mild dementia with L ewy
      bodies (DLB ) and mild A lzheimer's disease (AD ). METHODS: The present study
      included 37 mild DLB patients, 48 mild AD patients, and 80 healthy elderly
      individuals. A comprehensive battery of neuropsychological tests was
      administrated to assess their cognitive function. Linear stepwise discriminant
      analysis was used to identify the neuropsychological measures with values that
      could differentiate between mild DLB and mild AD . RESULTS: The mild DLB group
      had greater impairments in attention, executive function, and visuospatial
      ability, while mild AD patients performed significantly worse on memory tests.
      Linear stepwise discriminant analysis indicated that the M emory and E xecutive S
      creening's 5-min delayed recall test was the best neuropsychological
      discriminator between mild DLB and mild AD . CONCLUSIONS: Different patterns of
      cognitive impairment facilitate the differentiation of mild DLB from mild AD .
      For patients with mild dementia, better performance on the M emory and E xecutive
      S creening's 5-min delayed recall test suggests that the diagnosis is more likely
      DLB than AD .

PMID- 29372602
TI  - Why do older people refuse resuscitation? A qualitative study examining
      retirement village residents' resuscitation decisions.
AB  - BACKGROUND: There is a dearth of qualitative research on resuscitation
      preferences of older New Zealanders. The aim of this study was to investigate the
      resuscitation preferences of older New Zealanders in a retirement village or
      residential care setting, as well as the reasons for these preferences. METHODS:
      This study had 37 participants from two retirement villages in Auckland, New
      Zealand. Participants were interviewed about a hypothetical case vignette about
      cardiopulmonary resuscitation, and then they completed a semi-structured
      interview. Interviews were subsequently transcribed and analyzed by two
      independent researchers using thematic qualitative methodology. RESULTS: The
      majority of the participants (n = 25, 67.6%) decided against resuscitation, 10
      (27.0%) wanted resuscitation, and 2 (5.4%) were ambivalent about their
      resuscitation preferences. Three main themes emerged during the data analysis
      regarding participants' reasons for deciding against resuscitation: (i) the wish
      for a natural death; (ii) advanced age; and (iii) a realistic awareness about the
      consequences of resuscitation. Responses related to the third these had three
      subthemes: (i) reduced quality of life; (ii) loss of personal integrity and sense
      of existence; and (iii) concern that resuscitation could result in unnecessary
      costs or a burden on others. Among participants who preferred resuscitation, two
      main themes emerged regarding their reasons for wanting resuscitation: (i) the
      wish to prolong a good quality of life; and (ii) unrealistic expectations of
      resuscitation. CONCLUSIONS: Older people in this study were able to make reasoned
      decisions about resuscitation based on balancing their subjective estimations of
      quality of life and the presumed consequences of resuscitation. It is important
      therefore to educate older adults about the potential outcomes of resuscitation
      and explore (and document) their reasoning when discussing resuscitation
      preferences so their wishes can be respected.

PMID- 29372603
TI  - Information processing speed as a mediator between psychosocial stress and global
      cognition in older adults.
AB  - BACKGROUND: The link between psychosocial stress and cognitive function is
      complex, and previous studies have indicated that it may be mediated by
      processing speed. Therefore, the main aim of this study was to examine whether
      processing speed mediates the association between psychosocial stress and global
      cognition in older adults. Moreover, the moderating role of gender in this model
      is examined as well. METHODS: The study included 2322 community-dwelling older
      adults in Malaysia who were randomly selected through a multistage proportional
      cluster random sampling technique. Global cognition construct was measured by the
      Mini-Mental State Examination and Montreal Cognitive Assessment; psychosocial
      stress construct was measured by perceived stress, depression, loneliness, and
      neuroticism; and processing speed was assessed by the Digit Symbol Substitution
      Test. Structural equation modelling was used to analyze the mediation and
      moderation tests. RESULTS: Processing speed was found to partially mediate the
      relationship between psychosocial stress and global cognition (beta in the direct
      model = -0.15, P < 0.001; beta in the full mediation model = -0.11, P < 0.001).
      Moreover, the relationship between psychosocial stress and global cognition was
      found to be significant in men only, whereas the association between processing
      speed and global cognition was significant in men and women. CONCLUSIONS:
      Psychosocial stress may increase the likelihood that older adults will experience
      poor processing capacity, which could reduce their higher level cognition.
      Results indicate that there is a need to develop processing capacity intervention
      programmes for psychologically distressed older adults to prevent them from
      suffering cognitive decline.

PMID- 29372605
TI  - Effects of caffeinated alcoholic beverages with low alcohol and high caffeine
      content on cognitive and motor functions.

PMID- 29372604
TI  - Association between objectively measured chewing ability and frailty: A cross
      sectional study in central Thailand.
AB  - AIM: Limited data are available on the association between oral function and
      frailty, especially in developing countries. Additionally, the association
      between objectively assessed chewing function and frailty has not been well
      studied. The present cross-sectional study tested the hypothesis that objectively
      measured poor chewing ability is associated with frailty in community-dwelling
      older Thai adults. METHODS: The study population comprised 141 people in Nakhon
      Pathom, Thailand (median age 72 years). Demographic and clinical data were
      collected at a community center. Participants were asked to chew a gum designed
      for assessing chewing ability. The differences in gum color before and after
      chewing (DeltaE*ab) were calculated and used as the exposure variable, where a
      lower DeltaE*ab indicates lower chewing ability. Frailty phenotypes were defined
      by weakness, slowness, weight loss, low physical activity level and exhaustion
      components, and used as the outcome variable. Participants with three or more
      components were considered frail, and those with one or two components were
      considered pre-frail. Ordinal logistic regression analyses were carried out to
      assess the association of objective chewing ability with frailty. RESULTS: Of the
      141 participants, 32 (22.7%) were categorized as frail and 78 (55.3%) as pre
      frail. In the analysis adjusted for demographic and health characteristics, the
      adjusted odds ratio of the presence and severity of frailty was significantly
      higher in participants with lower DeltaE*ab (adjusted odds ratio for one decrease
      in DeltaE*ab 1.05, 95% confidence interval 1.01-1.10, P = 0.03). CONCLUSIONS:
      Objectively measured chewing ability was significantly associated with frailty in
      community-dwelling older Thai adults. Geriatr Gerontol Int 2018; 18: 860-866.

PMID- 29372606
TI  - A Versatile Ligand Platform for Palladium- and Nickel-Catalyzed Ethylene
      Copolymerization with Polar Monomers.
AB  - The ability to carry out transition-metal-catalyzed copolymerizations of olefins
      with polar monomers is a great challenge in the field of olefin polymerization.
      Palladium has been the dominant player in this field, while its low-cost nickel
      counterpart has only achieved very limited success. We report the synthesis and
      evaluation of a highly versatile platform based on diphosphazane monoxide
      ligands. Both palladium and nickel catalysts bearing these ligands mediate the
      copolymerization of ethylene with a number of fundamental polar monomers.

PMID- 29372607
TI  - Hepatobiliary and Pancreatic: Massive hepatic cystic echinococcosis compressing
      inferior vena cava.

PMID- 29372609
TI  - Gastrointestinal: Spontaneous air versus dye cholangiogram in bile duct stone
      disease.

PMID- 29372608
TI  - Gastrointestinal: Duodenal variceal bleeding secondary to thrombophilia-related
      portal vein thrombosis.

PMID- 29372610
TI  - Hepatobiliary and Pancreatic: Rare cause of obstructive jaundice by Trichosporon
      asahii.

PMID- 29372611
TI  - Tuning Aromaticity of para-Substituted Benzene Derivatives with an External
      Electric Field.
AB  - Substituent effects are phenomena which play an important role in organic
      chemistry, especially when aromatic species are considered. For this class of
      systems, the question of the interrelation between substituent effect and
      aromaticity arises. The relationship between aromaticity and substituent effects
      appears to be of a competitive nature. This work examines changes in aromaticity
      in para-substituted benzene derivatives exposed to external electric fields of
      various intensities. Three systems with different substituent electron
      accepting/donating properties are studied, namely p-aminophenol, p
      nitrobenzonitrile and p-nitrophenol. In these cases, the competitive character
      between substituent effects and aromaticity is emphasised. It is also shown that
      aromaticity (and the substituent effect) can be tuned using an external electric
      field applied to the system.

PMID- 29372613
TI  - PBJ publishes high-impact original plant biotechnology research with free global
      access.

PMID- 29372612
TI  - Statins decrease leptin expression in human white adipocytes.
AB  - Statin use is associated with increased calorie intake and consequent weight
      gain. It is speculated that statin-dependent improvements in lipid profile may
      undermine the perceived need to follow lipid-lowering and other dietary
      recommendations leading consequently to increased calorie intake. However,
      increases in calorie intake in statin users may also be related to statin
      dependent decreases in satiety factors such as leptin, an adipocyte-derived
      adipokine. The objective of our study was to examine the direct effects of
      statins on leptin expression. Adipocytes are the main source of circulating
      leptin. Therefore, we examined the effects of atorvastatin and simvastatin on
      leptin expression in cultured human white adipocytes. We show that treatment of
      white adipocytes with simvastatin and atorvastatin decreases leptin mRNA
      expression (simvastatin: P = 0.008, atorvastatin: P = 0.03) and leptin secretion
      (simvastatin: P = 0.0001, atorvastatin: P = 0.0001). Both simvastatin and
      atorvastatin mediate decreases in leptin expression via extracellular-signal
      regulated kinases 1/2 and peroxisome proliferator-activated receptor gamma
      pathways (simvastatin: P = 0.01, atorvastatin: P = 0.026). Additionally, statin
      treatment also induced expected increases in adiponectin, while decreasing
      monocyte chemoattractant protein 1 (MCP1) mRNA. Furthermore, statins increased
      secretion of both total as well as high molecular weight adiponectin while
      decreasing MCP1 secretion. To conclude, statins act directly on human white
      adipocytes to regulate adipokine secretion and decrease leptin expression. Leptin
      is an important satiety factor. Hence, statin-dependent decreases in leptin may
      contribute, at least in part, to increases in food intake in statin users.

PMID- 29372614
TI  - Corrigendum.

PMID- 29372615
TI  - Pattern of inpatient pediatric cardiology consultations in sub-Saharan Africa.
AB  - Malawi is one of the poorest nations in the world, ranked 151st among 195
      countries by the World Bank, with an under-5-year mortality rate of 63 per 1000
      live births. There are no previous studies describing the spectrum of inpatient
      pediatric cardiology consultations in sub-Saharan Africa. A descriptive cohort
      study was performed at Kamuzu Central Hospital (KCH), a tertiary care hospital in
      Lilongwe, Malawi. Demographic, anthropometric, and clinical information for all
      cardiology consults patients aged 0-18 years admitted to the children's wards
      over a period of 1 month was reviewed. Seventy-three consults and 69
      echocardiograms were performed on 71 patients (35 males, 38 females). The median
      (IQR) age was 3.1 years (9 months-10.5 years). About 53% (39/73) had failure to
      thrive, 4.1% (3/73) were sero-reactive for HIV and 100% (73/73) were fully
      immunized for age per the Expanded Program on Immunization schedule. Seventy-four
      percent of the echocardiograms were abnormal, with 34.8% (24/69) having
      congenital heart disease (CHD) and 18.8% (13/69) having acquired heart disease
      (AHD) with preserved cardiac function. Among CHD, 10.1% (7/69) had cyanotic CHD
      and 24.6% (17/769 had acyanotic CHD. Among AHD, 10.1% (7/69) had rheumatic heart
      disease with preserved cardiac function. Symptomatic systolic heart failure (HF)
      with ejection fraction <50%, was found in 20.3% (14/69), and pulmonary
      hypertension was diagnosed in 10.1% (7/69). Overall admission mortality was 5.5%
      (4/73). Three patients left the hospital against medical advice. None of the
      patients with systolic HF had CHD. There was no significant association of HIV,
      gender, or failure to thrive on presence of systolic HF. This is the first report
      describing the spectrum of pediatric cardiology consults in an inpatient setting
      in Malawi. There was an unexpectedly high proportion of CHD and systolic HF.
      Further studies should be conducted to explore the implications and potential
      causes of these findings.

PMID- 29372616
TI  - Hemodialysis quality metrics and patient-reported ability to work.

PMID- 29372618
TI  - Corrigendum.

PMID- 29372619
TI  - Inpatient care for emerging adults affected by mental health disorders.

PMID- 29372620
TI  - Decreased inappropriate shocks with new generation ICDs in children and patients
      with congenital heart disease.
AB  - OBJECTIVE: Inappropriate implantable cardioverter defibrillator (ICD) shocks in
      children and patients with congenital heart disease (CHD) remain a major
      complication of device therapy, occurring in as many as 50% of children with
      ICDs. New generation devices include algorithms designed to minimize
      inappropriate shocks. This study aimed to evaluate the effect of new generation
      ICDs on the incidence of inappropriate shocks in the pediatric and CHD
      population. DESIGN: Retrospective study of patients with CHD or under age 25
      receiving ICDs between 2000 and 2015. New generation ICDs were defined as those
      with Medtronic "SmartShock" algorithms. RESULTS: Two hundred eight devices were
      implanted in 146 patients. Rates of inappropriate shocks were similar between
      diagnoses (P = .71). The rate of inappropriate shock was 15% over median 5.8
      years follow-up. In the 36 patients (25%) with new generation ICDs, the rate of
      inappropriate shock was 6.3% over 4 years. Comparing old to new generation ICDs,
      freedom from first inappropriate shock was 90.6% versus 97.1% at 1 year and 80.4%
      versus 97.1% at 3 years (P = .01). Lead fracture was associated with having
      inappropriate shock (hazard ratio 8.5, P < .0001), and there was no significant
      difference between the device groups when lead fractures were excluded. Clinical
      actions were taken in 69% of patients after initial inappropriate shock (such as
      medication or program change, system revision, or explant). When an action was
      taken, subsequent inappropriate shock was reduced (5.3% vs 49.2% at 1 year; P =
      .002). CONCLUSIONS: Pediatric and CHD patients are experiencing reduced
      inappropriate shocks with new generation ICD systems, though reduced lead
      fracture may account for this improvement. Clinical interventions after
      inappropriate shock favorably impact the subsequent rate of shocks once an
      inappropriate shock occurs.

PMID- 29372621
TI  - A new year - and there's plenty in store for EJCC readers!

PMID- 29372622
TI  - Women's experiences of sexual functioning in the early weeks of breast cancer
      treatment.
AB  - This study describes women's sexual functioning in the early weeks of breast
      cancer treatment and the possible sexual changes that women may experience
      compared with pre-treatment functioning. Seventy-five patients filled out a
      questionnaire on sexual functioning and participated in a semi-structured
      interview on changes in sexual life and intimacy after treatment. Sixty-two women
      were sexually active before treatment; three post-treatment patterns of sexual
      behaviour were identified: 22.6% of these women were as active as before
      treatment, 35.5% stopped any sexual activity and 41.9% experienced quantitative
      and qualitative changes. Analyses showed that each pattern had specific
      characteristics regarding current sexual functioning, the kinds of changes
      reported (e.g. decreased frequency and increased tenderness) and the reasons for
      these changes (e.g. tiredness and sex not a priority). Even in the immediate post
      surgical period, women may react in very different ways to treatment in terms of
      sexual functioning. Most women experience changes, but cessation of sexual
      activity is not inevitable. Positive changes (growing tenderness and affection)
      also exist. These important interindividual differences require a person-centred
      approach when the topic of sexuality is being addressed, and practitioners need
      to be sensitive to individual perceptions of change. Early detection of sexual
      changes may prevent the crystallisation of difficulties over time.

PMID- 29372623
TI  - Underestimation of cancer incidence in Iran and necessity for establishing
      population-based cancer registries.

PMID- 29372624
TI  - Selective Hydrogenolysis of Furfural Derivative 2-Methyltetrahydrofuran into
      Pentanediol Acetate and Pentanol Acetate over Pd/C and Sc(OTf)3 Cocatalytic
      System.
AB  - It is of great significance to convert platform molecules and their derivatives
      into high value-added alcohols, which have multitudinous applications. This study
      concerns systematic conversion of 2-methyltetrahydrofuran (MTHF), which is
      obtained from furfural, into 1-pentanol acetate (PA) and 1,4-pentanediol acetate
      (PDA). Reaction parameters, such as the Lewis acid species, reaction temperature,
      and hydrogen pressure, were investigated in detail. 1 H NMR spectroscopy and
      reaction dynamics study were also conducted to help clarify the reaction
      mechanism. Results suggested that cleavage of the primary alcohol acetate was
      less facile than that of the secondary alcohol acetate, with the main product
      being PA. A PA yield of 91.8 % (150  degrees C, 3 MPa H2 , 30 min) was achieved
      by using Pd/C and Sc(OTf)3 as a cocatalytic system and an 82 % yield of PDA was
      achieved (150  degrees C, 30 min) by using Sc(OTf)3 catalyst. Simultaneously, the
      efficient conversion of acetic esters into alcohols by simple saponification was
      carried out and led to a good yield.

PMID- 29372625
TI  - The Effect of Dopant-Free Hole-Transport Polymers on Charge Generation and
      Recombination in Cesium-Bismuth-Iodide Solar Cells.
AB  - The photovoltaic characteristics of CsBi3 I10 -based solar cells with three
      dopant-free hole-conducting polymers are investigated. The effect on charge
      generation and charge recombination in the solar cells using the different
      polymers is studied and the results indicate that the choice of polymer strongly
      affects the device properties. Interestingly, for the solar cell with poly[[2,3
      bis(3-octyloxyphenyl)-5,8-quinoxalinediyl]-2,5-thiophenediyl] (TQ1), the photon
      to-current conversion spectrum is highly improved in the red wavelength region,
      suggesting that the polymer also contributes to the photocurrent generation in
      this case. This report provides a new direction for further optimization of Bi
      halide solar cells by using dopant-free hole-transporting polymers and shows that
      the energy levels and the interaction between the Bi-halide and the conducting
      polymers are very important for solar cell performance.

PMID- 29372626
TI  - Capecitabine/cisplatin versus 5-fluorouracil/cisplatin in Chinese patients with
      advanced and metastatic gastric cancer: Re-analysis of efficacy and safety data
      from the ML17032 phase III clinical trial.
AB  - AIM: To confirm non-inferiority and test potential superiority of
      capecitabine/cisplatin (XP) over 5-fluorouracil (5-FU)/cisplatin (FP) as first
      line treatment for advanced gastric cancer (AGC) in Chinese patients. METHODS: In
      open-label phase III ML17032 trial, AGC (stage IIIA-IV) patients with or without
      metastases were randomized 1:1 to receive cisplatin (80 mg/m2 /day intravenous
      [IV] day 1) with either capecitabine (1000 mg/m2 /day oral [PO] twice daily
      [BID], days 1-14; XP) or 5-FU (800 mg/m2 /day continuous IV days 1-5; FP) every 3
      weeks. The primary objective was to confirm the non-inferiority of XP over FP for
      progression-free survival (PFS). RESULTS: The intent-to-treat (ITT) population
      included 126 Chinese patients (XP-62, FP-64; 67.5% male, mean age 54.7 years).
      The primary analysis was performed on the per-protocol (PP) population (105
      patients; XP-51, FP-54; 65.7% male). Median PFS in the XP and FP groups was 7.2
      and 4.5 months, respectively. The adjusted hazard ratio (HR) for PFS was 0.52
      (95% confidence interval [CI]: 0.32-0.83, P = 0.006). Unadjusted HR for PFS in
      the ITT population was 0.63 (95% CI, 0.42-0.94, P = 0.022). The most frequent
      drug-related grade 3/4 adverse events (AEs) were neutropenia (XP-20.7%, FP-17.7%)
      and gastrointestinal disorders (XP-19.0%, FP-19.4%). The overall incidence of
      grade 3/4 AEs (XP-43.1%, FP-46.8%), serious AEs (XP-1.7%, FP-3.2%), and AEs
      related to treatment discontinuation (XP-10.3%, FP-16.1%) were comparable.
      CONCLUSION: XP had a similar safety profile and may demonstrate superiority for
      PFS compared to FP as first-line treatment of Chinese patients with AGC
      (NCT02563054).

PMID- 29372628
TI  - Antigen-Free Radionuclide-Embedded Gold Nanoparticles for Dendritic Cell
      Maturation, Tracking, and Strong Antitumor Immunity.
AB  - Dendritic cell (DC)-based cancer immunotherapy requires efficient maturation of
      DCs and sensitive monitoring of DCs localized in the lymph nodes that activate T
      cells. This paper reports a robust and simple surface chemistry for highly
      sensitive and stable radionuclide-embedded gold nanoparticles (Poly-Y-RIe-AuNPs)
      prepared with oligotyrosine-modified AuNPs with additional Au shell formation as
      a promising positron emission tomography/computed tomography imaging agent. The
      multiple oligotyrosine binding sites modified on AuNPs provide excellent
      stability for conjugated radioisotopes by forming an Au shell. They can be
      heavily conjugated with radioisotope iodine, which enables sensitive tracking of
      DCs in the lymphatic system. More importantly, it is found that the maturation of
      DCs is possible solely with Poly-Y-RIe-AuNPs without any additional stimulus for
      DC maturation. DCs matured by Poly-Y-RIe-AuNPs induce antitumor immunity to
      cervical cancer comparable to that produced from DCs pulsated with tumor lysates.
      These results demonstrate that the peptide-based surface chemistry of Poly-Y-RIe
      AuNPs is a simple and straightforward method to produce a highly sensitive and
      stable nuclear medicine imaging agent that also improves the efficiency of
      current antitumor immunotherapies.

PMID- 29372627
TI  - Leptin regulates disc cartilage endplate degeneration and ossification through
      activation of the MAPK-ERK signalling pathway in vivo and in vitro.
AB  - Recent findings demonstrate that leptin plays a significant role in chondrocyte
      and osteoblast differentiation. However, the mechanisms by which leptin acts on
      cartilage endplate (CEP) cells to give rise to calcification are still unclear.
      The aim of this study was to evaluate the effects of leptin that induced
      mineralization of CEP cells in vitro and in vivo. We constructed a rat model of
      lumbar disc degeneration and determined that leptin was highly expressed in the
      presence of CEP calcification. Rat CEP cells treated with or without leptin were
      used for in vitro analysis using RT-PCR and Western blotting to examine the
      expression of osteocalcin (OCN) and runt-related transcription factor 2 (Runx2).
      Both OCN and Runx2 expression levels were significantly increased in a dose- and
      time-dependent manner. Leptin activated ERK1/2 and STAT3 phosphorylation in a
      time-dependent manner. Inhibition of phosphorylated ERK1/2 using targeted siRNA
      suppressed leptin-induced OCN and Runx2 expression and blocked the formation of
      mineralized nodules in CEP cells. We further demonstrated that exogenous leptin
      induced matrix mineralization of CEP cells in vivo. We suggest that leptin
      promotes the osteoblastic differentiation of CEP cells via the MAPK/ERK signal
      transduction pathway and may be used to investigate the mechanisms of disc
      degeneration.

PMID- 29372629
TI  - Chest Tube Drainage of the Pleural Space: A Concise Review for Pulmonologists.
AB  - Chest tube insertion is a common procedure usually done for the purpose of
      draining accumulated air or fluid in the pleural cavity. Small-bore chest tubes
      (<=14F) are generally recommended as the first-line therapy for spontaneous
      pneumothorax in non-ventilated patients and pleural effusions in general, with
      the possible exception of hemothoraces and malignant effusions (for which an
      immediate pleurodesis is planned). Large-bore chest drains may be useful for very
      large air leaks, as well as post-ineffective trial with small-bore drains. Chest
      tube insertion should be guided by imaging, either bedside ultrasonography or,
      less commonly, computed tomography. The so-called trocar technique must be
      avoided. Instead, blunt dissection (for tubes >24F) or the Seldinger technique
      should be used. All chest tubes are connected to a drainage system device:
      flutter valve, underwater seal, electronic systems or, for indwelling pleural
      catheters (IPC), vacuum bottles. The classic, three-bottle drainage system
      requires either (external) wall suction or gravity ("water seal") drainage (the
      former not being routinely recommended unless the latter is not effective). The
      optimal timing for tube removal is still a matter of controversy; however, the
      use of digital drainage systems facilitates informed and prudent decision-making
      in that area. A drain-clamping test before tube withdrawal is generally not
      advocated. Pain, drain blockage and accidental dislodgment are common
      complications of small-bore drains; the most dreaded complications include organ
      injury, hemothorax, infections, and re-expansion pulmonary edema. IPC represent a
      first-line palliative therapy of malignant pleural effusions in many centers. The
      optimal frequency of drainage, for IPC, has not been formally agreed upon or
      otherwise officially established.

PMID- 29372630
TI  - What Can We Apply to Manage Acute Exacerbation of Chronic Obstructive Pulmonary
      Disease with Acute Respiratory Failure?
AB  - Acute exacerbation(s) of chronic obstructive pulmonary disease (AECOPD) tend to
      be critical and debilitating events leading to poorer outcomes in relation to
      chronic obstructive pulmonary disease (COPD) treatment modalities, and contribute
      to a higher and earlier mortality rate in COPD patients. Besides pro-active
      preventative measures intended to obviate acquisition of AECOPD, early recovery
      from severe AECOPD is an important issue in determining the long-term prognosis
      of patients diagnosed with COPD. Updated GOLD guidelines and recently published
      American Thoracic Society/European Respiratory Society clinical recommendations
      emphasize the importance of use of pharmacologic treatment including
      bronchodilators, systemic steroids and/or antibiotics. As a non-pharmacologic
      strategy to combat the effects of AECOPD, noninvasive ventilation (NIV) is
      recommended as the treatment of choice as this therapy is thought to be most
      effective in reducing intubation risk in patients diagnosed with AECOPD with
      acute respiratory failure. Recently, a few adjunctive modalities, including NIV
      with helmet and helium-oxygen mixture, have been tried in cases of AECOPD with
      respiratory failure. As yet, insufficient documentation exists to permit
      recommendation of this therapy without qualification. Although there are too few
      findings, as yet, to allow for regular andr routine application of those
      modalities in AECOPD, there is anecdotal evidence to indicate both mechanical and
      physiological benefits connected with this therapy. High-flow nasal cannula
      oxygen therapy is another supportive strategy which serves to improve the
      symptoms of hypoxic respiratory failure. The therapy also produced improvement in
      ventilatory variables, and it may be successfully applied in cases of hypercapnic
      respiratory failure. Extracorporeal carbon dioxide removal has been successfully
      attempted in cases of adult respiratory distress syndrome, with protective
      hypercapnic ventilatory strategy. Nowadays, it is reported that it was also
      effective in reducing intubation in AECOPD with hypercapnic respiratory failure.
      Despite the apparent need for more supporting evidence, efforts to improve
      efficacy of NIV have continued unabated. It is anticipated that these efforts
      will, over time, serve toprogressively decrease the risk of intubation and
      invasive mechanical ventilation in cases of AECOPD with acute respiratory
      failure.

PMID- 29372631
TI  - An Increased Proportion of Apoptosis in CD4+ T Lymphocytes Isolated from the
      Peripheral Blood in Patients with Stable Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND: The pathophysiology of chronic obstructive pulmonary disease (COPD)
      includes inflammation, oxidative stress, an imbalance of proteases and
      antiproteases and apoptosis which has been focused on lately. Abnormal apoptotic
      events have been demonstrated in both epithelial and endothelial cells, as well
      as in inflammatory cells including neutrophils and lymphocytes in the lungs of
      COPD patients. An increased propensity of activated T lymphocytes to undergo
      apoptosis has been observed in the peripheral blood of COPD patients. Therefore,
      the apoptosis of T lymphocytes without activating them was investigated in this
      study. METHODS: Twelve control subjects, 21 stable COPD patients and 15
      exacerbated COPD patients were recruited in the study. The T lymphocytes were
      isolated from the peripheral blood using magnetically activated cell sorting.
      Apoptosis of the T lymphocytes was assessed with flow cytometry using Annexin V
      and 7-aminoactinomycin D. Apoptosis of T lymphocytes at 24 hours after the cell
      culture was measured so that the T lymphocyte apoptosis among the control and the
      COPD patients could be compared. RESULTS: Stable COPD patients had increased
      rates of CD4+ T lymphocyte apoptosis at 24 hours after the cell culture, more
      than the CD4+ T lymphocyte apoptosis which appeared in the control group, while
      the COPD patients with acute exacerbation had an amplified response of CD4+ T
      lymphocyte apoptosis as well as of CD8+ T lymphocyte apoptosis at 24 hours after
      the cell culture. CONCLUSION: Stable COPD patients have more apoptosis of CD4+ T
      lymphocytes, which can be associated with the pathophysiology of COPD in stable
      conditions.

PMID- 29372632
TI  - Optimal wavelength selection for optical spectroscopy of hemoglobin and water
      within a simulated light-scattering tissue.
AB  - An algorithm that selects optimal wavelengths for spectral fitting of diffuse
      light reflectance spectra using a nonnegative least squares method is presented.
      Oxyhemoglobin, deoxyhemoglobin, and water are considered representative
      absorbers, but the approach is not constrained or limited by absorber selection
      provided native basis spectra are available. The method removes wavelengths
      iteratively from a scattering-modulated absorption matrix by maximizing the
      product of its singular values and offers considerable improvements over
      previously published wavelength selection schemes. Resulting wavelength
      selections are valid for a broad range of optical properties and yield lower RMS
      errors than other wavelength combinations. The method is easily modified and
      broadly applicable to tissue optical spectroscopy. Adaptation of the algorithm to
      select optimal light-emitting diodes for fitting blood is described.

PMID- 29372633
TI  - Meeting of the International Task Force for Disease Eradication, October 2017.

PMID- 29372634
TI  - Fact sheet on tuberculosis (updated January 2018).

PMID- 29372635
TI  - [Premature delivery and colonization associated with Ureaplasma parvum].

PMID- 29372636
TI  - [Vertebral osteomyelitis due to Actinomyces: a case report].

PMID- 29372637
TI  - Volatility and Chain Length Interplay of Primary Amines: Mechanistic
      Investigation on the Stability and Reversibility of Ammonia-Responsive Hybrid
      Perovskites.
AB  - Hybrid organic-inorganic perovskites possess promising signal transduction
      properties, which can be exploited in a variety of sensing applications.
      Interestingly, the highly polar nature of these materials, while being a bane in
      terms of stability, can be a boon for sensitivity when they are exposed to polar
      gases in a controlled atmosphere. However, signal transduction during sensing
      induces irreversible changes in the chemical and physical structure, which is one
      of the major lacuna preventing its utility in commercial applications. In the
      context of developing alkylammonium lead(II) iodide perovskite materials for
      sensing, here we address major issues such as reversibility of structure and
      properties, correlation between instability and properties of alkylamines, and
      relation between packing of alkyl chains inside the crystal lattice and the
      response time toward NH3 gas. The current investigation highlights that the vapor
      pressure of alkylamine formed in the presence of NH3 determines the reversibility
      and stability of the original perovskite lattice. In addition, close packing of
      alkyl chains inside the perovskite crystal lattice reduces the response toward
      NH3 gas. The mechanistic study addresses three important factors such as quick
      response, reversibility, and stability of perovskite materials in the presence of
      NH3 gas, which could lead to the design of stable and sensitive two-dimensional
      hybrid perovskite materials for developing sensors.

PMID- 29372638
TI  - Magnetic Phase Transition in Spark-Produced Ternary LaFeSi Nanoalloys.
AB  - Using the magnetocaloric effect in nanoparticles holds great potential for
      efficient refrigeration and energy conversion. The most promising candidate
      materials for tailoring the Curie temperature to room temperature are rare-earth
      based magnetic nanoalloys. However, only few high-nuclearity
      lanthanide/transition-metal nanoalloys have been produced so far. Here we report,
      for the first time, the observation of magnetic response in spark-produced LaFeSi
      nanoalloys. The results suggest that these nanoalloys can be used to exploit the
      magnetocaloric effect near room temperature; such a finding can lead to the
      creation of unique multicomponent materials for energy conversion, thus helping
      toward the realization of a sustainable energy economy.

PMID- 29372639
TI  - Genetic Relationships among Different Chemotypes of Lupinus sulphureus.
AB  - Lupines (Lupinus spp.) are a common plant legume species found on western U.S.
      rangelands. Lupinus spp. may contain quinolizidine and/or piperidine alkaloids
      that can be toxic and/or teratogenic to grazing livestock. Alkaloid profiles may
      vary between and within a species. The objectives of this study were to (1)
      further explore the characteristic alkaloid profiles of Lupinus sulphureus using
      field collections and (2) explore the phylogenetic relationship of the different
      populations and chemotypes of L. sulphureus using the amplified fragment length
      polymorphism method of DNA fingerprinting, thus providing possible explanations
      to the phenomena of multiple chemotypes within a species. A total of 49
      accessions of L. sulphureus were classified into seven chemotypes. The DNA
      profiles showed that one L. sulphureus chemotype, chemotype A, is genetically
      divergent from the other chemotypes of L. sulphureus, suggesting that it
      represents an unresolved lupine taxon, possibly a new lupine species.
      Additionally, the different chemotypes of L. sulphureus represented different
      genetic groups, as shown by Bayesian cluster analysis and principle component
      analysis.

PMID- 29372640
TI  - Thermodynamics of Halide Binding to a Neutral Bambusuril in Water and Organic
      Solvents.
AB  - Driving forces of anion binding in water in contrast to nonpolar environments are
      of high interest because of their relevance to biology and medicine. Here we
      report a neutral bambusuril macrocycle (1), soluble in both water and nonpolar
      solvents due to decoration with 12 polyethylene glycol-based substituents. The
      new bambusuril has the highest affinity for I- in pure water ever reported for a
      synthetic macrocycle relying on hydrogen bonding interactions rather than metal
      coordination or Coulombic forces. Isothermal titration calorimetry (ITC)
      experiments in nine different solvents, ranging from polar water to nonpolar
      carbon tetrachloride, provided insight into the forces responsible for halide
      binding by bambusurils. The different importance of anion solvation and solvent
      expulsion from the cavity of the macrocycle in various solvents is illustrated by
      the fact that halide binding in water and chloroform is exclusively driven by
      favorable enthalpy with an entropic penalty, while in alcohols and nonpolar
      solvents, both favorable enthalpy and entropy contribute to anion encapsulation.
      DFT calculations and correlation of thermodynamic data with the solvent Swain
      acity parameter further underscore the importance of solvent effects on anion
      binding by bambusurils.

PMID- 29372642
TI  - Abu-Sahl al-Masihi (died circa 1010 AD): The Persian physician in the early
      medieval era.
AB  - In the early medieval era, in the time which is called the Islamic Golden Age,
      medicine flourished through the practice of Persian physicians (9th to 12th
      century AD). Abu-Sahl al-Masihi (died circa 1010 AD) was one of the physicians in
      that period who had great influence on the progress of medicine by his own
      writings as well as his influence on great scholars like Biruni and Avicenna as
      their teacher. He was a polymath and had many writings in various fields of
      science, in particular medical sciences. Some of his manuscripts in medicine were
      Al-Mia fil-Tibb (Book of the Hundred), Kitab al-Teb al-Koli (The General
      Medicine), Ezhar al-Hekmat Allah Ta'ala fi Khalgh al-Ensan (God's Mystery on the
      Creation of Man), Resalat al-Adwiya (Treatise of Drugs), Osool Elm Nabz (the
      Principles of Pulse), and Resala f i Tahqiq Amral-Waba' (On the determination of
      the matter of infectious diseases). As a sign of his impact in Persian medicine,
      many later physicians (until 19th century) referred to and cited his works in
      their manuscripts several times.

PMID- 29372641
TI  - Enhanced Metal-Insulator Transition Performance in Scalable Vanadium Dioxide Thin
      Films Prepared Using a Moisture-Assisted Chemical Solution Approach.
AB  - Vanadium dioxide (VO2) is a strong-correlated metal-oxide with a sharp metal
      insulator transition (MIT) for a range of applications. However, synthesizing
      epitaxial VO2 films with desired properties has been a challenge because of the
      difficulty in controlling the oxygen stoichiometry of VO x, where x can be in the
      range of 1 < x < 2.5 and V has multiple valence states. Herein, a unique moisture
      assisted chemical solution approach has been developed to successfully manipulate
      the oxygen stoichiometry, to significantly broaden the growth window, and to
      significantly enhance the MIT performance of VO2 films. The obvious broadening of
      the growth window of stoichiometric VO2 thin films, from 4 to 36  degrees C, is
      ascribed to a self-adjusted process for oxygen partial pressure at different
      temperatures by introducing moisture. A resistance change as large as 4 orders of
      magnitude has been achieved in VO2 thin films with a sharp transition width of
      less than 1  degrees C. The much enhanced MIT properties can be attributed to the
      higher and more uniform oxygen stoichiometry. This technique is not only
      scientifically interesting but also technologically important for fabricating
      wafer-scaled VO2 films with uniform properties for practical device applications.

PMID- 29372643
TI  - Child with cerebral malformations and epilepsy.
AB  - PURPOSE: Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a rare
      autosomal dominant genetic disorder involving multiple organ systems and
      primarily characterized by structural brain abnormalities and a distinctive
      facial appearance. METHODS: To study the clinical characteristics, gene types and
      seizures of BWCFF. The natural history, clinical data and peripheral blood sample
      were collected in the child and his patients. To screen the beta-actin gene
      (ACTB) of a newly diagnosed child, hoping to find the gene mutation. RESULTS: The
      child had left ptosis, ocular hypertelorism, arched eyebrows, only 30% of the
      left ear hearing, a slight hypotonia, normal muscle strength, walking
      instability. The seizures were difficult to control with antiepileptic drugs and
      presented some degree of psychomotor development delay. Genetic screening showed
      De Novo in ACTB gene (c.484A> G, p.Thr162Ala). Parents did not detect related
      gene mutations. CONCLUSIONS: Patients with typical facial features and cerebral
      cortical malformations associated with refractory epilepsy should be highly
      suspected BWCFF. Patients are advised to carry out genetic screening to confirm
      the diagnosis.

PMID- 29372645
TI  - Martha Wollstein: A pioneer American female clinician-scientist.
AB  - Martha Wollstein was not only the first fully specialized pediatric perinatal
      pathologist practicing exclusively in a North America children's hospital, she
      also blazed another pathway as a very early pioneer female clinician-scientist.
      Wollstein provided patient care at Babies Hospital of New York City from 1891
      until her retirement in 1935, and also simultaneously worked for many years as a
      basic scientist at the prestigious Rockefeller Institute for Medical Research.
      Wollstein published over 65 papers, many frequently cited, during her career on a
      wide range of topics including pediatric and infectious diseases. Wollstein was a
      rare female in the field of pathology in an era when just a relatively small
      number of women became doctors in any medical specialty. Wollstein was born into
      an affluent Jewish American family in New York City in 1868 and graduated from
      the Women's Medical College in 1889. This paper explores her family support and
      ethnic and religious background, which helped facilitate her professional
      success. During her time, she was recognized internationally for her research and
      was respected for her medical and scientific skills; unfortunately today her
      important career has been largely forgotten.

PMID- 29372644
TI  - Quantitative assessment of demyelination in ischemic stroke in vivo using
      macromolecular proton fraction mapping.
AB  - A recent MRI method, fast macromolecular proton fraction (MPF) mapping, was used
      to quantify demyelination in the transient middle cerebral artery occlusion
      (MCAO) rat stroke model. MPF and other quantitative MRI parameters (T1, T2,
      proton density, and apparent diffusion coefficient) were compared with
      histological and immunohistochemical markers of demyelination (Luxol Fast Blue
      stain, (LFB)), neuronal loss (NeuN immunofluorescence), axonal loss (Bielschowsky
      stain), and inflammation (Iba1 immunofluorescence) in three animal groups ( n = 5
      per group) on the 1st, 3rd, and 10th day after MCAO. MPF and LFB optical density
      (OD) were significantly reduced in the ischemic lesion on all days after MCAO
      relative to the symmetrical regions of the contralateral hemisphere. Percentage
      changes in MPF and LFB OD in the ischemic lesion relative to the contralateral
      hemisphere significantly differed on the first day only. Percentage changes in
      LFB OD and MPF were strongly correlated (R = 0.81, P < 0.001) and did not
      correlate with other MRI parameters. MPF also did not correlate with other
      histological variables. Addition of T2 into multivariate regression further
      improved agreement between MPF and LFB OD (R = 0.89, P < 0.001) due to correction
      of the edema effect. This study provides histological validation of MPF as an
      imaging biomarker of demyelination in ischemic stroke.

PMID- 29372646
TI  - Correction to: Finley et al., Evaluation of tremolite asbestos exposures
      associated with the use of commercial products.

PMID- 29372647
TI  - Corrigendum.

PMID- 29372648
TI  - Pulse pressure and blood pressure components:. Is the sum more than the parts?

PMID- 29372649
TI  - Differential expression of snoRNAs in oral squamous cell carcinomas: new
      potential diagnostic markers.
AB  - BACKGROUND: Small nucleolar RNAs (snoRNAs) are small non-coding RNA sequences
      whose most studied function is ribosome biogenesis. The altered expression of
      snoRNA is observed in tumoral processes such as breast cancer and multiple
      myeloma. However, we have not found any references to snoRNAs in oral squamous
      cell carcinomas (OSCC) in the literature at the time this article was written.
      MATERIAL AND METHODS: We have analyzed snoRNA expression in frozen OSCC tissue
      samples and have compared them to healthy controls. RNA was extracted from a
      total of eight OSCC samples and eight control samples, measuring the differential
      expression of small RNAs with the Affymetrix(r) miRNA 4.1 Array Plate microarray
      platform. RESULTS: Results were analyzed using the Transcriptome Analysis Console
      3.0 (TAC) software. We obtained a total of 16 deregulated snoRNAs of which one
      was over expressed and 15 were under expressed. SnoRNAs expression was altered in
      OSCC and could serve as a diagnostic marker.

PMID- 29372650
TI  - Dr Catherine Louisa Corbett MB ChB DPH (1877-1960), Diary in Serbia. Her work
      with the Scottish Women's Hospitals in Serbia and Russia, 1915-1917.
AB  - Catherine Corbett was the second woman to gain a medical degree from the
      University of Manchester Medical School in 1905; however, little was known about
      her life or work, apart from the fact that she was a School Medical Inspector
      (SMI) and never married. The rediscovery of her Diary in Serbia (1916) has
      revealed her work for the Scottish Women's Hospitals (SWH) during the First World
      War in Serbia (1915-1916). Her time alongside her female colleagues was a good
      experience, however the harsh conditions, especially those she experienced during
      a further period working in Russia (1916-1917), left her exhausted and
      psychologically stressed. After the war, her job as a SMI in Burnley and her
      pursuit of rock climbing helped her adjust to a normal life and allowed her to
      promote her views on female education.

PMID- 29372652
TI  - Francis I. Proctor, MD and his wife Elizabeth C. Proctor: Their lives and legacy.
AB  - The Francis I. Proctor Foundation for Research in Ophthalmology is
      internationally recognized for its research in the fields of ocular inflammatory
      and infectious diseases. Although the name of one of its founders, Francis I.
      Proctor, MD (1864-1936) is memorialized, the legacy of his wife, Elizabeth C.
      Proctor (1882-1975) is not as well known. They were both full partners in this
      endeavor. Francis, a successful and wealthy ophthalmologist, retired to Santa Fe,
      New Mexico. After their marriage, they became interested in the problem of
      blinding trachoma, then an endemic problem on the Native American Indian
      reservations. The couple selected Phillips Thygeson, MD (1903-2002), a young
      ophthalmologist with an interest in infectious diseases, as their lead
      investigator. Using their own funds, the Proctors paid for Thygeson and
      themselves to study trachoma in Egypt, and then establish a trachoma research
      laboratory in Arizona where the causative agent of trachoma was identified. Not
      only did the Proctors fund these studies, they also studied bacteriology so they
      could help in the laboratory themselves. After Francis' death, Elizabeth endowed
      the Foundation in 1947 and continued to support it. She also established the
      Proctor Medal for The Association for Research in Vision and Ophthalmology.

PMID- 29372651
TI  - Gamma-glutamyltransferase, possible novel biomarker in colon diverticulosis: a
      case-control study.
AB  - The gamma-glutamyltransferase (GGT) is recognized in medical practice as a useful
      indicator for the detection of liver lesions, especially those induced by the
      excessive consumption of alcoholic or cholesterol-associated drinks. The present
      study, although it includes a very small number of cases diagnosed with colon
      diverticulosis-diverticulitis associated with polyposis at the same intestinal
      level, identifies the presence of increased circulating concentrations of this
      enzyme in the serum. Its serum levels are tracked "dynamically" throughout a year
      after the diagnosis and start of the therapy. The study calls into question the
      release of the enzyme from the edge of the enterocytes' brush-like edge, leading
      to the pathogenic disturbance of regional redox homeostasis. The hypothesis gives
      the circulating values of GGT predictive value for cellular oxidative stress, as
      well as for indirectly expressing the glutathione level in cytosol.

PMID- 29372653
TI  - Mortimer Frank, Johann Ludwig Choulant, and the history of anatomical
      illustration.
AB  - Mortimer Frank (1874-1919) was an ophthalmologist in Chicago, Illinois. He
      published a number of papers on the history of medicine, and was secretary of the
      Chicago Society of the History of Medicine and editor of their Bulletin. His
      major contribution to the history of medicine relates to the history of
      anatomical illustration. The classic book on that subject had been published in
      1852 in German by the physician and historian, Johann Ludwig Choulant (1791
      1861). However, by Frank's time this text was both out dated and out of print.
      Frank took on the tremendous project of translating Choulant's German text into
      English as History and Bibliography of Anatomic Illustration in Its Relation to
      Anatomic Science and The Graphic Arts. He improved Choulant's text with the
      results of his and other scholars' research, greatly enlarging the text. Frank
      supplemented the original book with a biography of Choulant, essays on anatomists
      not considered in the original text, and an essay on the history of anatomical
      illustration prior to those authors discussed by Choulant. This book, now
      referred to as Choulant/Frank, has been reprinted several times, and is still
      useful as a reference in this field, though some of its research is now dated.

PMID- 29372654
TI  - Functional TSH receptor antibodies in children with autoimmune thyroid diseases.
AB  - INTRODUCTION: The diagnostic value of the level of TSH receptor antibodies (TSHR
      Ab) in the population of children with autoimmune thyroid diseases (AITDs) is
      still unknown. The aim of this cross-sectional study was to investigate the
      prevalence of TSHR-Ab in a paediatric cohort with AITD and healthy controls.
      MATERIALS AND METHODS: A total of 240 serum samples were obtained from 205
      patients with AITD, type 1 diabetes (T1D), juvenile arthritis (JA), and healthy
      controls (C). TSHR stimulating (TSI) and -blocking (TBI) immunoglobulins were
      measured in cell-based bioassays using CHO cells expressing a chimeric TSHR and a
      c-AMP response-element-dependent luciferase. TSI was reported as percentage of
      specimen-to-reference ratio (cutoff 140SRR%). Blocking activity was defined as
      percent inhibition of luciferase expression relative to induction with bovine TSH
      alone (40% inhibition). RESULTS: C as well as children with JA and T1D were both
      TSI and TBI negative. In contrast, children with Graves' disease (GD) were
      positive for TSI in 47/53 samples (88.7%) while those with thyroidal and orbital
      GD showed TSI positivity in 95.8% (23/24 samples). Serum TSI levels were SRR% 320
      +/- 157 and 417 +/- 135 in GD and GD + orbitopathy, respectively (p = .02).
      Children with Hashimoto's thyroiditis (HT) were TSI positive in 4/83 (4.8%)
      samples, including two with orbital involvement. TSI levels were increased in HT
      children with vs. those without eye disease (SRR% 177 vs. 51, p < .01). In
      comparison, TBI were negative in all tested samples of children with GD but
      positive in one HT sample. CONCLUSIONS: In conclusion, TSI is prevalent in
      children with GD while the highest serum TSI levels were noted in children with
      AITD and orbitopathy.

PMID- 29372655
TI  - Optogenetic investigation of the variable neurovascular coupling along the
      interhemispheric circuits.
AB  - The interhemispheric circuit connecting the left and the right mammalian brain
      plays a key role in integration of signals from the left and the right side of
      the body. The information transfer is carried out by modulation of simultaneous
      excitation and inhibition. Hemodynamic studies of this circuit are inconsistent
      since little is known about neurovascular coupling of mixed excitatory and
      inhibitory signals. We investigated the variability in hemodynamic responses
      driven by the interhemispheric circuit during optogenetic and somatosensory
      activation. We observed differences in the neurovascular response based on the
      stimulation site - cell bodies versus distal projections. In half of the
      experiments, optogenetic stimulation of the cell bodies evoked a predominant post
      synaptic inhibition in the other hemisphere, accompanied by metabolic oxygen
      consumption without coupled functional hyperemia. When the same transcallosal
      stimulation resulted in predominant post-synaptic excitation, the hemodynamic
      response was biphasic, consisting of metabolic dip followed by functional
      hyperemia. Optogenetic suppression of the postsynaptic excitation abolished the
      coupled functional hyperemia. In contrast, light stimulation at distal
      projections evoked consistently a metabolic response. Our findings suggest that
      functional hyperemia requires signals originating from the cell body and the
      hemodynamic response variability appears to reflect the balance between the post
      synaptic excitation and inhibition.

PMID- 29372657
TI  - A Message from the Editor-in-Chief.

PMID- 29372656
TI  - Conjugation of phosphonoacetic acid to nucleobase promotes a mechanism-based
      inhibition.
AB  - Small molecule inhibitors have a powerful blocking action on viral polymerases.
      The bioavailability of the inhibitor, nevertheless, often raise a significant
      selectivity constraint and may substantially limit the efficacy of therapy.
      Phosphonoacetic acid has long been known to possess a restricted potential to
      block DNA biosynthesis. In order to achieve a better affinity, this compound has
      been linked with natural nucleotide at different positions. The structural
      context of the resulted conjugates has been found to be crucial for the
      acquisition by DNA polymerases. We show that nucleobase-conjugated
      phosphonoacetic acid is being accepted, but this alters the processivity of DNA
      polymerases. The data presented here not only provide a mechanistic rationale for
      a switch in the mode of DNA synthesis, but also highlight the nucleobase-targeted
      nucleotide functionalization as a route for enhancing the specificity of small
      molecule inhibitors.

PMID- 29372658
TI  - Acute and sublethal effects of organophosphate insecticide chlorpyrifos on
      freshwater fish Oreochromis niloticus.
AB  - Chlorpyrifos is a widely used organosphosphate insecticide in India. Residue of
      the insecticide is frequently detected in trace to moderate concentration in food
      grains and in surface water of different freshwater ecosystems of the country. In
      this study, 96 h LC50 of the technical grade (94% a.i.) and commercial
      formulation (20% EC) of chlorpyrifos to freshwater fish Oreochromis niloticus
      were determined as 90.0 and 42.0 ug/L based on 2 h actual concentration of
      chlorpyrifos in water. About 96 h exposure to sublethal concentrations (0, 12.0
      and 25.0 MUg/L) of the commercial formulation (20% EC) of chlorpyrifos reduced
      the level of hepatic glycogen, activities of alkaline phosphatase,
      acetylcholinesterase, and catalase in liver and elevated the level of plasma
      glucose and activities of hepatic acid phosphatase, aspartate aminotransferase,
      and alanine aminotransferase in O. niloticus. About 28-day exposure to these sub
      lethal concentrations caused anemia in fish, while 90 days exposure reduced
      growth of the fish and carcass concentration of crude protein and crude lipid as
      compared to control. It was concluded from this study that commercial formulation
      of chlorpyrifos (20% EC) was highly toxic to O. niloticus. Exposure to sub-lethal
      concentrations of the insecticide could induce oxidative stress and anemia
      resulting in reduced growth of the fish.

PMID- 29372659
TI  - Novel anti-inflammatory and analgesic agents: synthesis, molecular docking and in
      vivo studies.
AB  - Twelve new derivatives of benzothiazole bearing benzenesulphonamide and
      carboxamide were synthesised and investigated for their in vivo anti
      inflammatory, analgesic and ulcerogenic activities. Molecular docking showed an
      excellent binding interaction of the synthesised compounds with the receptors,
      with 17c showing the highest binding energy (-12.50 kcal/mol). Compounds 17c and
      17i inhibited carrageenan-induced rat paw oedema at 72, 76, and 80% and 64, 73,
      and 78% at 1 h, 2 h, and 3 h, respectively. In the analgesic activity experiment,
      compounds 17c, 17 g, and 17i had ED50 (uM/kg) of 96, 127, and 84 after 0.5 h;
      102, 134, and 72 after 1 h and 89, 156, and 69 uM/kg after 2 h, respectively,
      which were comparable with 156, 72, and 70 uM/kg for celecoxib. The ulcerogenic
      index of the most active derivatives 17c and 17i were 0.82 and 0.89,
      respectively, comparable to 0.92 for celecoxib. The physicochemical studies of
      the new derivatives showed that they will not have oral bioavailability problems.

PMID- 29372661
TI  - Goethe: A bipolar personality? Periodicity of affective states in Johann Wolfgang
      von Goethe as reflected by Paul Julius Mobius.
AB  - This paper aims to investigate the character and etiological basis of German poet
      Johann Wolfgang von Goethe's mental disorder. From 1898, German neuropsychiatrist
      Paul Julius Mobius developed the hypothesis that Goethe's work provided several
      hints for the notion that the German poet suffered from a distinct bipolar
      disorder. The paper investigates Mobius's psychopathographic study on Goethe and
      his hypothesis of a mood periodicity in Goethe against the mirror of modern
      concepts. Mobius came to the conclusion that Goethe's illness was bipolar in
      character and became visible at intervals of seven years and lasted for about two
      years. The majority of Mobius's contemporary psychiatric colleagues (Emil
      Kraepelin, Max Isserlin, Ernst Kretschmer, Josef Breuer) supported this view
      which has still not been convincingly challenged. In present-day terms, Mobius's
      hypothesis can be best mirrored as a subclinical foundation of mood disorder.
      Furthermore, with his extensive study, Mobius disproved the common notion that
      Goethe had suffered from an illness as the result of a syphilitic infection.

PMID- 29372662
TI  - QSAR modelling using combined simple competitive learning networks and RBF neural
      networks.
AB  - The aim of this study was to propose a QSAR modelling approach based on the
      combination of simple competitive learning (SCL) networks with radial basis
      function (RBF) neural networks for predicting the biological activity of chemical
      compounds. The proposed QSAR method consisted of two phases. In the first phase,
      an SCL network was applied to determine the centres of an RBF neural network. In
      the second phase, the RBF neural network was used to predict the biological
      activity of various phenols and Rho kinase (ROCK) inhibitors. The predictive
      ability of the proposed QSAR models was evaluated and compared with other QSAR
      models using external validation. The results of this study showed that the
      proposed QSAR modelling approach leads to better performances than other models
      in predicting the biological activity of chemical compounds. This indicated the
      efficiency of simple competitive learning networks in determining the centres of
      RBF neural networks.

PMID- 29372660
TI  - Current challenges for cancer vaccine adjuvant development.
AB  - INTRODUCTION: Although much progress has been made in the last decade(s) toward
      development of effective cancer vaccines, there are still important obstacles to
      therapeutic successes. New generations of cancer vaccines will benefit from a
      combination adjuvant approach that targets multiple branches of the immune
      response. Areas covered: Herein we describe how combinatorial adjuvant strategies
      can help overcome important obstacles to cancer vaccine development, including
      antigen immunogenicity and tumor immune suppression. Tumor antigens may be both
      tolerogenic and may utilize active mechanisms to suppress host immunity,
      including downregulation of MHC molecules to evade recognition and upregulation
      of immune inhibitory receptors, to subvert an effective immune response. The
      current cancer vaccine literature was surveyed to identify advancements in the
      understanding of the biological mechanisms underlying poor antigen immunogenicity
      and tumor immune evasion, as well as adjuvant strategies designed to overcome
      them. Expert commentary: Poor immunogenicity of tumor antigens and tumor immune
      evasion mechanisms make the design of cancer vaccines challenging. Growing
      understanding of the tumor microenvironment and associated immune responses
      indicate the importance of augmenting not only the effector response, but also
      overcoming the endogenous regulatory response and tumor evasion mechanisms.
      Therefore, new vaccines will benefit from multi-adjuvanted approaches that
      simultaneously stimulate immunity while preventing inhibition.

PMID- 29372663
TI  - Eugenol, a plant-derived phenolic nutraceutical, protects thiol (SH) group in
      myocardium from ROS-mediated oxidation under chemotherapeutic stress induced by
      arsenic trioxide - a in vivo model study.
AB  - Arsenic trioxide is an effective chemotherapeutic agent for the treatment of
      acute promyelocytic leukemia. The clinical usefulness of arsenic trioxide is
      narrow due to different organ toxicities. It is hypothesized that the generation
      of reactive oxygen species by arsenic trioxide leads to thiol-based oxidative
      damage in rat myocardium. In this study, the defensive effect of eugenol on thiol
      based oxidative stress was investigated in arsenic trioxide-treated rats. Rats
      were orally administered with arsenic trioxide (4 mg/kg per day) alone and in
      combination with eugenol (5 mg/kg per day) for 30 days. Reduction in relative
      organ weight, total thiol level, protein thiol content, acid-soluble thiol
      content, thioredoxin activity, and protein content was witnessed in arsenic
      trioxide-treated rats. Additionally, the total antioxidant activity, tissue GSH
      level, and GSH/GSSG ratio were considerably diminished. However, the co-treatment
      of eugenol noticeably sheltered the arsenic trioxide-mediated cardiotoxicity. In
      conclusion, eugenol is a prospective phenolic compound, of natural origin, for
      protecting the thiol group in myocardium from oxidative stress by
      chemotherapeutic compounds.

PMID- 29372664
TI  - Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: A
      systematic review and meta-analysis.
AB  - Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2)
      inhibitors on cardiovascular outcomes have not been well established. We pooled
      evidence from all available clinical trials to assess the cardiovascular effects
      of this drug. Design A systematic review and meta-analysis of randomised
      controlled trials. Methods We queried electronic databases (MEDLINE, Scopus,
      CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published
      and unpublished placebo controlled trials of SGLT2 inhibitors. Only studies with
      a follow-up period of at least 24 weeks and reporting at least one cardiovascular
      outcome were included. Results from trials were presented as odds ratios (ORs)
      with 95% confidence intervals (CIs) and were pooled using a random-effects model.
      Results Thirty-five eligible studies (canagliflozin, nine; empagliflozin, eight;
      dapagliflozin, 18), consisting of 34,987 patients with type 2 diabetes mellitus
      were included. Pooled results show that SGLT2 inhibitors, when compared to
      placebo, significantly reduce all-cause mortality (OR 0.79, 95% CI 0.70-0.89; P <
      0.001), major adverse cardiac events (OR 0.8, 95% CI 0.76-0.92; P < 0.001), non
      fatal myocardial infarction (OR 0.85, 95% CI 0.73-0.98; P = 0.03) and heart
      failure/hospitalisation for heart failure (OR 0.67, 95% CI 0.59-0.76; P < 0.001)
      in patients with type 2 diabetes mellitus. No significant difference was noted in
      the occurrence of stroke (OR 1.02, 95% CI 0.85-1.21; P = 0.87), atrial
      fibrillation (OR 0.61, 95% CI 0.31-1.19; P = 0.15) or unstable angina (OR 0.95,
      95% CI 0.73-1.25; P = 0.73). In addition, there was no heterogeneity between
      different drugs in the SGLT2 inhibitor class for all of the clinical outcomes
      studied ( I2 = 0). Conclusions SGLT2 inhibitors significantly reduce the
      incidence of mortality, major adverse cardiac events, non-fatal myocardial
      infarction and heart failure in patients with type 2 diabetes mellitus. Subtypes
      of SGLT2 inhibitors appear to have similar cardiovascular effects.

PMID- 29372666
TI  - Christiaan Barnard's personal attitude to apartheid.

PMID- 29372665
TI  - DNA methylation of the Oct4A enhancers in embryonal carcinoma cells after
      etoposide treatment is associated with alternative splicing and altered
      pluripotency in reversibly senescent cells.
AB  - The epigenetic mechanisms underlying chemoresistance in cancer cells resulting
      from drug-induced reversible senescence are poorly understood. Chemoresistant ESC
      like embryonal carcinoma PA1 cells treated with etoposide (ETO) were previously
      found to undergo prolonged G2 arrest with transient p53-dependent upregulation of
      opposing fate regulators, p21CIP1 (senescence) and OCT4A (self-renewal). Here we
      report on the analysis of the DNA methylation state of the distal enhancer (DE)
      and proximal enhancer (PE) of the Oct4A gene during this dual response. When
      compared to non-treated controls the methylation level increased from 1.3% to
      12.5% and from 3% to 19.4%, in the DE and PE respectively. It included CpG and
      non-CpG methylation, which was not chaotic but presented two patterns in each
      enhancer. Discorrelating with methylation of enhancers, the transcription of
      Oct4A increased, however, a strong expression of the splicing form Oct4B was also
      induced, along with down-regulation of the Oct4A partners of in the
      pluripotency/self-renewal network Sox2 and Lin28. WB demonstrated disjoining of
      the OCT4A protein from the chromatin-bound fraction. In survival clones,
      methylation of the DE was considerably erased, while some remnant of methylation
      of the PE was still observed. The alternative splicing for Oct4B was reduced,
      Oct4A level insignificantly decreased, while the expression of Sox2 and Lin28
      recovered, all three became proportionally above the control. These findings
      indicate the involvement of the transient patterned methylation of the Oct4A
      enhancers and alternative splicing in the adaptive regulation of cell fate choice
      during the p53-dependant dual state of reversible senescence in ESC-like cancer
      stem cells.

PMID- 29372667
TI  - Living with asthma in 19th-century France: The doctor, Armand Trousseau, and the
      patient, Emile Pereire.
AB  - Major advances in the French medical system following the French Revolution have
      stimulated a rich historiography of which Michel Foucault's Naissance de la
      clinique: une archeologie du regard medical (1963) and Erwin H. Ackerknecht's
      Medicine at the Paris Hospital, 1794-1848 (1967) are of lasting significance.
      Changes in the organisation and structure of hospitals accompanied the
      development and availability of new medical technologies and procedures and
      encouraged a more intense study of the aetiology and pathology of disease.
      Theories about asthma and its treatment profited from this dynamic environment as
      Classical Greek doctrines about the effect of the humours on bodily imbalance
      gave way to an increasingly more precise understanding of the nature and cause of
      asthma. The clinician and teacher, Armand Trousseau (1801-1867), who held the
      chair of Clinical Medicine at the Hotel-Dieu in Paris and was himself an
      asthmatic, promoted new theories about the illness and developed innovative ways
      of dealing with its effects. Among his patients was the banker and financier,
      Emile Pereire (1800-1875), a lifelong asthmatic. Based on the Pereire Family
      Archives (hereafter AFP), the case of Emile Pereire provides a preface to the
      later case of that other, more famous, asthmatic, Marcel Proust.

PMID- 29372668
TI  - The ciliary protein RPGRIP1L governs autophagy independently of its proteasome
      regulating function at the ciliary base in mouse embryonic fibroblasts.
AB  - Previously, macroautophagy/autophagy was demonstrated to be regulated inter alia
      by the primary cilium. Mutations in RPGRIP1L cause ciliary dysfunctions resulting
      in severe human diseases summarized as ciliopathies. Recently, we showed that
      RPGRIP1L deficiency leads to a decreased proteasomal activity at the ciliary base
      in mice. Importantly, the drug-induced restoration of proteasomal activity does
      not rescue ciliary length alterations in the absence of RPGRIP1L indicating that
      RPGRIP1L affects ciliary function also via other mechanisms. Based on this
      knowledge, we analyzed autophagy in Rpgrip1l-negative mouse embryos. In these
      embryos, autophagic activity was decreased due to an increased activation of the
      MTOR complex 1 (MTORC1). Application of the MTORC1 inhibitor rapamycin rescued
      dysregulated MTORC1, autophagic activity and cilia length but not proteasomal
      activity in Rpgrip1l-deficient mouse embryonic fibroblasts demonstrating that
      RPGRIP1L seems to regulate autophagic and proteasomal activity independently from
      each other.

PMID- 29372669
TI  - Evolutionary conservation of DNA methylation in CpG sites within ultraconserved
      noncoding elements.
AB  - Ultraconserved noncoding elements (UCNEs) constitute less than 1 Mb of vertebrate
      genomes and are impervious to accumulating mutations. About 4000 UCNEs exist in
      vertebrate genomes, each at least 200 nucleotides in length, sharing greater than
      95% sequence identity between human and chicken. Despite extreme sequence
      conservation over 400 million years of vertebrate evolution, we show both ordered
      interspecies and within-species interindividual variation in DNA methylation in
      these regions. Here, we surveyed UCNEs with high CpG density in 56 species
      finding half to be intermediately methylated and the remaining near 0% or 100%.
      Intermediately methylated UCNEs displayed a greater range of methylation between
      mouse tissues. In a human population, most UCNEs showed greater variation than
      the LINE1 transposon, a frequently used epigenetic biomarker. Global methylation
      was found to be inversely correlated to hydroxymethylation across 60 vertebrates.
      Within UCNEs, DNA methylation is flexible, conserved between related species, and
      relaxed from the underlying sequence selection pressure, while remaining
      heritable through speciation.

PMID- 29372670
TI  - RNA polymerase I activation and hibernation: unique mechanisms for unique genes.
AB  - In yeast, transcription of ribosomal DNA (rDNA) by RNA polymerase I (Pol I) is
      regulated by unique mechanisms acting at the level of the enzyme. Under stress
      situations such as starvation, Pol I hibernates through dimerization. When growth
      conditions are restored, dimer disassembly and Rrn3 binding drive enzyme
      activation and subsequent recruitment to rDNA.

PMID- 29372671
TI  - Capital social de los padres de escolares de una zona vulnerable.
AB  - El capital social supone importantes inversiones materiales, simbolicas y de
      esfuerzos. Conocer el capital social de una comunidad puede facilitar la
      comprension del beneficio de las relaciones comunitarias para la promocion de
      salud. Con el objetivo de reconocer los componentes del capital social de padres
      de escolares atendiendo una escuela en una zona vulnerable de la ciudad de
      Cordoba, Argentina, indagamos a traves de grupos focales acerca de elementos
      esenciales del capital social. La asintonia socio-cultural entre los pobladores
      originarios y los reubicados, la estigmatizacion policial y el clientelismo
      politico han generado desconfianza del uno hacia el otro en diferentes aspectos
      convivenciales, siendo la familia la unica red de apoyo. La escuela se reconoce
      como espacio adonde la gente espontaneamente se organiza para invertir en redes
      sociales, presentandose asi con potencialidad para la promocion de conductas
      saludables, por el lugar simbolico que ocupa para los padres.

PMID- 29372673
TI  - Impact of ageing on problem size and proactive interference in arithmetic facts
      solving.
AB  - Arithmetic facts (AFs) are required when solving problems such as "3 * 4" and
      refer to calculations for which the correct answer is retrieved from memory.
      Currently, two important effects that modulate the performance in AFs have been
      highlighted: the problem size effect and the proactive interference effect. The
      aim of this study is to investigate possible age-related changes of the problem
      size effect and the proactive interference effect in AF solving. To this end, the
      performance of young and older adults was compared in a multiplication production
      task. Furthermore, an independent measure of proactive interference was assessed
      to further define the architecture underlying this effect in multiplication
      solving. The results indicate that both young and older adults were sensitive to
      the effects of interference and of the problem size. That is, both interference
      and problem size affected performance negatively: the time needed to solve a
      multiplication problem increases as the level of interference and the size of the
      problem increase. Regarding the effect of ageing, the problem size effect remains
      constant with age, indicating a preserved AF network in older adults.
      Interestingly, sensitivity to proactive interference in multiplication solving
      was less pronounced in older than in younger adults suggesting that part of the
      proactive interference has been overcome with age.

PMID- 29372674
TI  - The effect of offset cues on saccade programming and covert attention.
AB  - Salient peripheral events trigger fast, "exogenous" covert orienting. The
      influential premotor theory of attention argues that covert orienting of
      attention depends upon planned but unexecuted eye-movements. One problem with
      this theory is that salient peripheral events, such as offsets, appear to summon
      attention when used to measure covert attention (e.g., the Posner cueing task)
      but appear not to elicit oculomotor preparation in tasks that require overt
      orienting (e.g., the remote distractor paradigm). Here, we examined the effects
      of peripheral offsets on covert attention and saccade preparation. Experiment 1
      suggested that transient offsets summoned attention in a manual detection task
      without triggering motor preparation planning in a saccadic localisation task,
      although there were a high proportion of saccadic capture errors on "no-target"
      trials, where a cue was presented but no target appeared. In Experiment 2, "no
      target" trials were removed. Here, transient offsets produced both attentional
      facilitation and faster saccadic responses on valid cue trials. A third
      experiment showed that the permanent disappearance of an object also elicited
      attentional facilitation and faster saccadic reaction times. These experiments
      demonstrate that offsets trigger both saccade programming and covert attentional
      orienting, consistent with the idea that exogenous, covert orienting is tightly
      coupled with oculomotor activation. The finding that no-go trials attenuates
      oculomotor priming effects offers a way to reconcile the current findings with
      previous claims of a dissociation between covert attention and oculomotor control
      in paradigms that utilise a high proportion of catch trials.

PMID- 29372672
TI  - Rooted tRNAomes and evolution of the genetic code.
AB  - We advocate for a tRNA- rather than an mRNA-centric model for evolution of the
      genetic code. The mechanism for evolution of cloverleaf tRNA provides a root
      sequence for radiation of tRNAs and suggests a simplified understanding of code
      evolution. To analyze code sectoring, rooted tRNAomes were compared for several
      archaeal and one bacterial species. Rooting of tRNAome trees reveals conserved
      structures, indicating how the code was shaped during evolution and suggesting a
      model for evolution of a LUCA tRNAome tree. We propose the polyglycine hypothesis
      that the initial product of the genetic code may have been short chain
      polyglycine to stabilize protocells. In order to describe how anticodons were
      allotted in evolution, the sectoring-degeneracy hypothesis is proposed. Based on
      sectoring, a simple stepwise model is developed, in which the code sectors from a
      1->4->8->~16 letter code. At initial stages of code evolution, we posit strong
      positive selection for wobble base ambiguity, supporting convergence to 4-codon
      sectors and ~16 letters. In a later stage, ~5-6 letters, including stops, were
      added through innovating at the anticodon wobble position. In archaea and
      bacteria, tRNA wobble adenine is negatively selected, shrinking the maximum size
      of the primordial genetic code to 48 anticodons. Because 64 codons are recognized
      in mRNA, tRNA-mRNA coevolution requires tRNA wobble position ambiguity leading to
      degeneracy of the code.

PMID- 29372676
TI  - Comparison of miRNA Evolution and Function in Plants and Animals.
AB  - MicroRNAs (miRNAs), as a major player in post-transcriptional regulation of gene
      expression, have been reported to regulate a broad variety of key biological
      processes, including growth, development and stress responses in both plants and
      animals. While the biogenesis and regulatory abilities of miRNAs have been
      extensively studied, the evolutionary history of miRNAs still needs more
      exploration. So far, several models explain the origination of plant and animal
      MIRNA (MIR) genes. Both inter-species and intra-species conservation and
      divergence of miRNAs exhibits functional adaptation to changing environments in
      evolution. Here we summarize recent progress in how these similarities and
      differences contribute to the characteristic features of miRNA evolution in the
      two kingdoms.

PMID- 29372677
TI  - [A woman with acute abdominal pain after a gastric bypass].
AB  - A 35-year-old woman with a history of gastric bypass presented with acute
      abdominal pain, nausea and an urge to move. She showed normal vital signs. We
      found abdominal guarding and elevated ASAT, ALAT and LDH. A CT scan showed the
      whirl sign, caused by a mesenteric herniation through the Roux-en-Y gastric
      bypass.

PMID- 29372678
TI  - [A Papua New Guinean with three foot ulcers].
AB  - A 25-year-old Papuan presented with three painless foot ulcers with undermined
      edges, induration and oedema. The appearance was typical for Buruli ulcer, which
      is caused by Mycobacterium ulcerans. A smear was positive for acid fast bacilli.
      Buruli ulcers are found in patients from humid and tropical regions and are
      treated with rifampicin and streptomycin during eight weeks.

PMID- 29372679
TI  - [Spontaneous clinical improvement in a COPD patient].
AB  - BACKGROUND: Bullous lung emphysema is a progressive disease, which may be partly
      explained by gradual expansion of bullae. These air-spaces arise after
      destruction of alveolar lung tissue. In some patients, bullae can merge into a
      giant bulla comprising more than 30% of the hemithorax. This bulla compresses
      surrounding relatively healthy lung parenchyma and regression results in
      improvement of pulmonary function, exertional tolerance and quality of life. This
      can be achieved with medication, surgery and with new experimental bronchoscopic
      lung volume reduction therapy. CASE DESCRIPTION: A 58-year-old man presented at
      the outpatient clinic because of exertion-induced dyspnoea. Additional
      diagnostics revealed bullous lung emphysema in which the left lower lobe had been
      transformed into a single large bulla over the course of 7 years of monitoring.
      His exertional tolerance continued to decrease gradually until there was an
      unexpected spectacular improvement of his lung function. This improvement proved
      to be caused by spontaneous resorption of the bulla. CONCLUSION: Patients with
      severe bullous lung emphysema may benefit from resorption of large bullae. This
      mostly requires treatment, but resorption sometimes can be a spontaneous
      occurrence.

PMID- 29372680
TI  - Antimicrobial Drug Resistance in Fish Pathogens.
AB  - Major concerns surround the use of antimicrobial agents in farm-raised fish,
      including the potential impacts these uses may have on the development of
      antimicrobial-resistant pathogens in fish and the aquatic environment. Currently,
      some antimicrobial agents commonly used in aquaculture are only partially
      effective against select fish pathogens due to the emergence of resistant
      bacteria. Although reports of ineffectiveness in aquaculture due to resistant
      pathogens are scarce in the literature, some have reported mass mortalities in
      Penaeus monodon larvae caused by Vibrio harveyi resistant to trimethoprim
      sulfamethoxazole, chloramphenicol, erythromycin, and streptomycin. Genetic
      determinants of antimicrobial resistance have been described in aquaculture
      environments and are commonly found on mobile genetic elements which are
      recognized as the primary source of antimicrobial resistance for important fish
      pathogens. Indeed, resistance genes have been found on transferable plasmids and
      integrons in pathogenic bacterial species in the genera Aeromonas, Yersinia,
      Photobacterium, Edwardsiella, and Vibrio. Class 1 integrons and IncA/C plasmids
      have been widely identified in important fish pathogens (Aeromonas spp., Yersinia
      spp., Photobacterium spp., Edwardsiella spp., and Vibrio spp.) and are thought to
      play a major role in the transmission of antimicrobial resistance determinants in
      the aquatic environment. The identification of plasmids in terrestrial pathogens
      (Salmonella enterica serotypes, Escherichia coli, and others) which have
      considerable homology to plasmid backbone DNA from aquatic pathogens suggests
      that the plasmid profiles of fish pathogens are extremely plastic and mobile and
      constitute a considerable reservoir for antimicrobial resistance genes for
      pathogens in diverse environments.

PMID- 29372683
TI  - The role of statins as therapeutic agents in cancer.
AB  - Statins are the inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase. This enzyme catalyzes conversion of HMG-CoA to mevalonate, which are
      the intermediates in cholesterol biosynthetic pathway. Statins also play an
      important role in carcinogenesis, because they are able to affect the cancer cell
      metabolism. Their effect has been observed in several cellular processes, such as
      angiogenesis, metastasis, apoptosis and cell proliferation. However, these
      effects are highly dependent on type of cancer and individual statins vary in
      their antitumor potential. This review summarizes the recent epidemiological
      evidence and preclinical studies that showed effects of all clinically used
      statins in vitro and in vivo. We also consider the results of different
      observational and retrospective studies focused on association among statins and
      cancer risk which are still under open discussion.

PMID- 29372682
TI  - The role of CYP17A1 in prostate cancer development: structure, function,
      mechanism of action, genetic variations and its inhibition.
AB  - Androgens play an important role during the development of both normal prostate
      epithelium and prostate cancer and variants of genes involved in androgen
      metabolism may be related to an increased risk of prostate disease. Cytochrome
      P450 17alpha-hydroxylase/17,20-lyase (CYP17A1) is a key regulatory enzyme in the
      steroidogenic pathway; it catalyses both 17alpha-hydroxylase and 17,20-lyase
      activities and is essential for the production of both androgens and
      glucocorticoids. In this review, we focus on the structure and enzymatic activity
      of CYP17A1 and the mechanism of modulation of CYP17A1 activities. We discuss the
      relationship between common genetic variations in CYP17A1 gene and prostate
      cancer risk and the main effects of these variations on the prediction of
      susceptibility and clinical outcomes of prostate cancer patients. The mechanism
      of action, the efficacy and the clinical potential of CYP17A1 inhibitors in
      prostate cancer are also summarized.

PMID- 29372681
TI  - CtBP impedes JNK- and Upd/STAT-driven cell fate misspecifications in regenerating
      Drosophila imaginal discs.
AB  - Regeneration following tissue damage often necessitates a mechanism for cellular
      re-programming, so that surviving cells can give rise to all cell types
      originally found in the damaged tissue. This process, if unchecked, can also
      generate cell types that are inappropriate for a given location. We conducted a
      screen for genes that negatively regulate the frequency of notum-to-wing
      transformations following genetic ablation and regeneration of the wing pouch,
      from which we identified mutations in the transcriptional co-repressor C-terminal
      Binding Protein (CtBP). When CtBP function is reduced, ablation of the pouch can
      activate the JNK/AP-1 and JAK/STAT pathways in the notum to destabilize cell
      fates. Ectopic expression of Wingless and Dilp8 precede the formation of the
      ectopic pouch, which is subsequently generated by recruitment of both anterior
      and posterior cells near the compartment boundary. Thus, CtBP stabilizes cell
      fates following damage by opposing the destabilizing effects of the JNK/AP-1 and
      JAK/STAT pathways.

PMID- 29372684
TI  - Role of S-adenosylmethionine cycle in carcinogenesis.
AB  - Alterations in enzymatic activities underlying the cellular capacity to maintain
      functional S-adenosylmethionine (SAM) cycle are associated with modified levels
      of its constituents. Since SAM is the most prominent donor of methyl group for
      sustaining the methylation pattern of macromolecules by methyltransferases, its
      availability is an essential prerequisite for sustaining the methylation pattern
      of nucleic acids and proteins. In addition, increased intracellular
      concentrations of S-adenosylhomocysteine and homocysteine, another two
      constituents of SAM cycle, exerts an inhibitory effect on the enzymatic activity
      of methyltranferases. While methylation pattern of DNA and histones is considered
      as an important regulatory hallmark in epigenetically regulated gene expression,
      amended methylation of several cellular proteins, including transcription
      factors, affects their activity and stability. Indeed, varied DNA methylome is a
      common consequence of disturbed SAM cycle and is linked with molecular changes
      underlying the transformation of the cells that may underlay the carcinogenesis.
      Here we summarize the recent evidences about the impact of disturbed SAM cycle on
      carcinogenesis.

PMID- 29372685
TI  - DNA methylation as mechanism of apoptotic resistance development in endometrial
      cancer patients.
AB  - DNA methylation is a significant epigenetic modification which plays a key role
      in regulation of gene expression and influences functional changes in endometrial
      tissue. Aberrant DNA methylation changes result in deregulation of important
      apoptotic proteins during endometrial carcinogenesis and apoptosis resistance
      development. Evading apoptosis is still a major problem in the successful
      treatment of endometrial cancer patients. The aim of our study was to examine the
      promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid
      endometrial cancer patients, precancerous lesions and healthy tissue from various
      normal menstrual cycle phases using a unique pre-designed methylation platform.
      We observed as the first a significant difference in promoter DNA methylation
      status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05)
      during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of
      normal menstrual cycle. The results of our study indicate that deregulation of
      mitochondrial apoptotic pathway can considerably contributes to the apoptosis
      resistance development and may be helpful in identifying of new potent biomarkers
      in endometrial cancer.

PMID- 29372686
TI  - Proton MR spectroscopic imaging of human glioblastomas at 1.5 Tesla.
AB  - In this study we evaluated clinical feasibility of proton magnetic resonance
      spectroscopy metabolite mapping (1H MRSI) by using 1.5 Tesla MR-scanner in 10
      patients with high-grade glioblastoma. In vivo 1H MRSI performed with a
      relatively short scan time of 20 minutes enabled to obtain comprehensive
      information about metabolic changes in glioblastoma and adjacent tissues namely
      in the peritumoral edema, in the middle and solid part of the tumor, and in the
      normal-appearing brain tissue. Spectroscopically it was possible to identify
      initiation of neuronal cell death in the solid tumorous tissue via decreased N
      acetyl-aspartate to creatine ratio (? tNAA/tCr) and expanding carcinogenesis
      reflected in elevated choline ratios (? tCho/tCr and tCho/tNAA). We showed also
      the central necrosis of glioblastoma accompanied by the tissue hypoxia, which
      were apparent as increased lactate and lipids ratios (? Lac/tCr and lip/Lac).
      Metabolic changes were noticeable also in the peritumoral area, showing the
      glioblastoma infiltration into the surrounding tissues. In intracranial tumors,
      1H MRSI performed on 1.5 Tesla field strength was sufficient to provide
      information about the stage of carcinogenesis, tumor expansion or necrotization
      and thus it could be considered as a useful diagnostic tool in oncology.

PMID- 29372687
TI  - Cyclin-dependent kinase 2 inhibitor SU9516 increases sensitivity of colorectal
      carcinoma cells Caco-2 but not HT29 to BH3 mimetic ABT-737.
AB  - Colorectal carcinoma (CRC) that represents one of the major causes for cancer
      related death in humans is often associated with over-expression of anti
      apoptotic proteins of Bcl-2 family. The aim of presented study was to determine
      the effect of ABT-737 inhibitor of anti-apoptotic proteins Bcl-2, Bcl-XL and Bcl
      w as well as cyclin-dependent kinase 2 (CDK2) inhibitor SU9516 alone and in
      combination with ABT-737 on survival of colorectal cell lines HT29 and Caco-2. We
      have shown that both Caco-2 and HT29 cells that are relatively resistant to ABT
      737 are also partially sensitive to SU9516, which increased sensitivity of Caco-2
      but not HT29 cells to ABT-737. Increased sensitivity of Caco-2 cells to ABT-737
      after addition of SU9516 correlated well with SU9516-induced decrease of Mcl-1
      expression while we have not observed downregulation of Mcl-1 after the treatment
      of HT29 cells with SU9516. Instead of this, we have shown that treatment of HT29
      cells with SU9516 is associated with decreased expression of tumour suppressor
      protein p53. Our findings provide a rationale for clinical use of Bcl-2 family
      inhibitors in combination with CDK2 inhibitors for treatment of Mcl-1-dependent
      colorectal tumours associated with expression of Bcl-2, Bcl-XL and Bcl-w
      proteins. In addition, we have shown potential of CDK2 inhibitors for treatment
      of tumours expressing R273H mutant p53.

PMID- 29372688
TI  - Testosterone as a prospective predictor of pathological Gleason score and
      pathological stage in prostate cancer.
AB  - The aim of the study was to assess the relationship between preoperative
      circulating levels of total serum testosterone and pathological Gleason score and
      pathological stage in prostate cancer patients who underwent radical retropubic
      prostatectomy. The levels of total serum testosterone were measured in the
      morning just before surgery in a group of 201 prostate cancer patients.
      Multinomial logistic regression models were used to model the association between
      total preoperative testosterone (individually or in combination with other
      preoperative predictors such as age, PSA, clinical stage and biopsy Gleason
      score) and pathological Gleason score, pathological stage in prostate cancer
      patients. The association between age and total testosterone was modelled by
      robust regression. The total serum testosterone, in combination with other
      prognostic factors (age, PSA, clinical stage and biopsy Gleason score) in models,
      was not statistically significant predictor of pathological Gleason score and
      pathological stage. The highly significant relationship between age and
      preoperative total testosterone was observed (p = 0). In prostate cancer
      patients, the level of total serum testosterone increased with age. In
      conclusion, total testosterone is not a statistically significant predictive
      factor for pathological Gleason score and pathological stage.

PMID- 29372689
TI  - DPYD genotype and haplotype analysis and colorectal cancer susceptibility in a
      case-control study from Slovakia.
AB  - Dihydropyrimidine dehydrogenase (DPD) acts as the first-step enzyme catabolizing
      pyrimidines in vivo. DPYD gene mutations interfere with the breakdown of uracil
      and thymine. Genetic variations of DPYD can cause an enzyme deficiency state,
      which results in severe toxicity or other adverse side effects such as DNA damage
      or RNA damage caused by imbalance of the nucleotide pool. Our case-control study
      investigates the possible association between seven DPYD gene polymophisms
      (rs1801267, rs72547602, rs1801160, rs3918290, rs1801159, rs1801158, rs1801265)
      and risk of colorectal cancer (CRC). The association analysis for DPD was
      performed on 273 CRC patients and 187 healthy controls. There is significant
      allele association of SNP rs1801160 with colorectal cancer (p = 0.003, OR =
      3.264, 95% CI = 1.425-7.475) in present analysis. Haplotype analysis of four DPYD
      polymorphisms showed significant difference in the distribution "IISt" haplotype
      between cases and controls. In comparison to the most common haplotype (VISt),
      the "IISt" haplotype was associated with increased risk for CRC (p = 0.038, OR =
      2.733, 95% CI = 1.019-7.326). The present study suggests that the SNP rs1801160
      and the "IISt" haplotype in the DPYD gene may also have a role in colorectal
      cancer risk.

PMID- 29372691
TI  - Prediction of radiation necrosis in a rodent model using magnetic resonance
      imaging apparent transverse relaxation ([Formula: see text]).
AB  - BACKGROUND AND PURPOSE: Radiation necrosis remains an irreversible long-term side
      effect following radiotherapy to the brain. The ability to predict areas that
      could ultimately develop into necrosis could lead to prevention and management of
      radiation necrosis. MATERIALS AND METHODS: Fischer 344 rats were irradiated using
      two platforms (micro-CT irradiator and x-Rad 225 IGRT) with radiation up to 30 Gy
      for the micro-CT and 40 Gy for the xRAD-224 to half the brain. Animals were
      subsequently imaged using a 9.4 T MRI scanner every 2-4 weeks for up to 28 weeks
      using a 7-echo gradient echo sequence. The apparent transverse relaxation
      constant ([Formula: see text]) was calculated and retrospectively analyzed.
      RESULTS: Animals irradiated with the low-dose rate micro-CT did not exhibit any
      symptoms or imaging changes associated with RN. Animals irradiated with the xRAD
      225 exhibited imaging changes consistent with RN at week 24. Analysis of the
      [Formula: see text] coefficient within the lesion and hippocampus shows the
      potential for detection of RN up to 10 weeks prior to morphological changes.
      CONCLUSIONS: The ability to predict areas of RN and increases of [Formula: see
      text] within the hippocampus provides a method for long-term monitoring and
      prediction of RN.

PMID- 29372690
TI  - Association of single nucleotide polymorphisms in FGF-RAS/MAP signalling cascade
      with breast cancer susceptibility.
AB  - The fibroblast growth factor receptors (FGFRs) and Ras/mitogen activated protein
      (RAS/MAP) signalling cascades are the main molecular pathways involved in breast
      carcinogenesis. This study aims to determine the association between FGF10
      (rs4415084 C>T), FGFR2 (rs2981582 C>T) and MAP3K1 (rs889312 A>C) gene
      polymorphisms and breast cancer, to analyse the discriminative ability of each
      SNP and to test the accuracy of the predictive breast cancer risk model which
      includes all SNPs. We conducted a case-control study of 170 women (57.06 +/-
      11.60 years) with histologically confirmed breast cancer and 146 controls (50.24
      +/- 10.69 years). High resolution melting (HRM) method with Sanger sequencing
      validation was used in analyses. We have revealed significant association of
      FGFR2 and MAP3K1 polymorphisms with breast cancer. The odds ratio of FGFR2 T
      allele was 1.897 (95% CI 1.231-2.936, p = 0.004) and MAP3K1 C allele 1.804 (95%
      CI 1.151-2.845, p = 0.012). FGFR2 polymorphism achieved the best discriminative
      ability (41.95%). The Random Forest algorithm selected FGFR2, MAP3K1 and age as
      important breast cancer predictors. The accuracy of this prediction model
      approached moderate accuracy (70%), with 35.9% sensitivity and 88.6% specificity.

PMID- 29372692
TI  - Numerical implementation of magneto-acousto-electrical tomography (MAET) using a
      linear phased array transducer.
AB  - In this study, the performance and implementation of magneto-acousto-electrical
      tomography (MAET) is investigated using a linear phased array (LPA) transducer.
      The goal of MAET is to image the conductivity distribution in biological bodies.
      It uses the interaction between ultrasound and a static magnetic field to
      generate velocity current density distribution inside the body. The resultant
      voltage due to velocity current density is sensed by surface electrodes attached
      on the body. In this study, the theory of MAET is reviewed. A 16-element LPA
      transducer with 1 MHz excitation frequency is used to provide beam directivity
      and steerability of acoustic waves. Different two-dimensional numerical models of
      breast and tumour are formed to analyze the multiphysics problem coupled with
      acoustics and electromagnetic fields. In these models, velocity current density
      distributions are obtained for pulse type ultrasound excitations. The static
      magnetic field is assumed as 1 T. To sense the resultant voltage caused by the
      velocity current density, it is assumed that two electrodes are attached on the
      surface of the body. The performance of MAET is shown through sensitivity matrix
      analysis. The sensitivity matrix is obtained for two transducer positions with 13
      steering angles between [Formula: see text] to [Formula: see text] with [Formula:
      see text] angular intervals. For the reconstruction of the images, truncated
      singular value decomposition method is used with different signal-to-noise ratio
      (SNR) values (20 dB, 40 dB, 60 dB and 80 dB). The resultant images show that the
      perturbation (5 mm  *  5 mm) placed 35 mm depth can be detected even if the SNR
      is 20 dB.

PMID- 29372693
TI  - Small bowel transanal evisceration mimicking a rectal prolapse. A case report and
      review of literature.
AB  - : Transanal intestinal evisceration is a very uncommon and dramatic occurrence,
      linked most frequently to rectal prolapse rupture or, very rarely, to traumatic
      pathology. The Authors describe a case of a 74-year-old female patient who
      required urgent hospital admission because of a seemingly strangulated rectal
      prolapse. During surgical preparation the protruding mass was recognized as small
      bowel loops herniating from the anus. Evisceration was due to spontaneous rectal
      wall rupture, most likely caused by increased abdominal pressure and consequent
      breach through the weakened rectum. Surgical treatment consisted in small bowel
      resection combined with an Hartmann's procedure. Spontaneous rectal rupture
      without a pre-existing rectal prolapse is a rather infrequent and challenging
      condition; its mechanism is still incompletely explained. The management is
      surgical and may range from primary repair up to extensive intestinal resection
      to include a defunctioning colostomy. KEY WORDS: Rectal prolapse, Spontaneous
      rectal rupture, Transanal evisceration.

PMID- 29372694
TI  - Dundee takes mouth cancer campaign further.

PMID- 29372695
TI  - Under cover.

PMID- 29372697
TI  - Special feature: Crisis at Christmas Dental Service 2017.

PMID- 29372698
TI  - Oral health: The loss of Jimmy Steele.

PMID- 29372703
TI  - Strategy and initiatives launch event held in Greater Manchester.

PMID- 29372706
TI  - Erratum.

PMID- 29372705
TI  - Mike Curtis: 'It's criminal that we still have such high levels of childhood
      caries'.

PMID- 29372707
TI  - Orthodontics: Hammer horror.

PMID- 29372710
TI  - Robert Timperley 1922-2017.

PMID- 29372708
TI  - Flowable composite as fissure sealing material? A systematic review and meta
      analysis.
AB  - Objectives The aim of this systematic review and meta-analysis was to evaluate
      fissure sealant retention in clinical studies in which investigators used
      flowable composites as pit and fissure sealants compared with conventional resin
      based pit and fissure sealants.Data sources and data selection The authors
      conducted a literature search (all articles published until April 13, 2017) to
      identify studies for inclusion in this systematic review. They assessed the
      quality of the evidence provided by using the modified Jadad scale and performed
      meta-analyses by using a random-effects model.Data extraction and data synthesis
      The authors found 11 studies that met the inclusion criteria for the systematic
      review and nine studies that could be used for the meta-analysis. Of the 11
      studies identified in the systematic review, four scored as having a low risk of
      bias, and seven scored as having a medium risk of bias. Our meta-analysis showed
      a significant positive effect of using flowable composites as a fissure sealant
      material (odds ratio, 2.387 [95% CI, 1.047, 5.444; P = 0.039]).Conclusion It
      seems that the use of flowable composite as a fissure sealing material can
      slightly increase the retention rate of sealants compared with conventional resin
      based sealants.

PMID- 29372711
TI  - Dentists on film: Pardon Us.

PMID- 29372714
TI  - Reunite with former King's classmates this March.

PMID- 29372715
TI  - UK dental practices are struggling to fill roles.

PMID- 29372716
TI  - New national dental implant standards.

PMID- 29372717
TI  - Conference report: Strategies for creating a collaborative network in research
      and teaching: CEDACORE.

PMID- 29372719
TI  - Paediatric dentistry: Dental Check by One.

PMID- 29372723
TI  - Dendritic phospholipid-based drug delivery systems.
AB  - A class of new dendritic phospholipid compounds with different hydrophilic
      dendritic poly(l-lysine) peripheries from generations 1 (G1) to 3 (G3) (DPL-1 to
      DPL-3) were synthesised and nano-drug delivery systems based on these compounds
      were prepared (DPN-2 and DPN-3). DPL-1 couldn't self-assemble into nanocarriers.
      The size, TEM image, and the CD spectrum of DPN-2 and DPN-3 were experimentally
      examined. The effect of the peripheral structure of dendritic phospholipid-based
      nanocarriers on their biological performance and drug delivery efficiency was
      studied. In vitro cytotoxicity studies demonstrated that the DOX-loaded DPN-3
      shows higher cytotoxicity against 4T1 cells and BGC823 cells than DPN-2. DOX
      loaded DPN-3 also showed excellent behaviours in cell internalization and 4T1
      multicellular spheroid penetration. The composition of the hydrophilic block in
      dendritic phospholipids affected the self-assembly behaviour, properties and
      delivery efficiency of the formed nanocarriers. This work will be helpful for
      building drug delivery systems with characteristics of high delivery efficiency
      and low cytotoxicity for clinical applications.

PMID- 29372720
TI  - Dental radiography: Acceptable radiographs.

PMID- 29372724
TI  - Uptake of fatty acids by a single endothelial cell investigated by Raman
      spectroscopy supported by AFM.
AB  - In this work, confocal Raman imaging was used to study the formation of lipid
      droplets (LDs) in vitro in a single endothelial cell upon incubation with
      polyunsaturated fatty acids (10 or 25 MUM) including arachidonic acid (AA) and
      its deuterated analog (AA-d8), eicosapentaenoic acid (EPA) and docosahexaenoic
      acid (DHA). Based on the Raman spectra obtained from a single endothelial cell,
      it was possible to investigate biochemical changes induced by addition of
      polyunsaturated fatty acids. In particular, the content of lipids in the formed
      LDs and the unsaturation degree were identified by Raman spectroscopy by marker
      bands at 1660 cm-1 due to the C[double bond, length as m-dash]C stretching and at
      ~3015 cm-1 due to the stretching mode of [double bond, length as m-dash]C-H
      associated with C[double bond, length as m-dash]C double bonds (except for a
      deuterated form where these bands are shifted respectively). To establish if the
      exogenous fatty acid was taken up by the cell and stored in LDs, a deuterium
      labelled polyunsaturated fatty acid was used. AA-d8 shows characteristic bands at
      around 2200-2300 cm-1 assigned to the [double bond, length as m-dash]C-D
      stretching modes. We established the uptake of AA and the accumulation of EPA
      into newly formed LDs in the endothelial cells. In contrast, no accumulation of
      DHA in LDs was observed even though LDs were formed upon DHA incubation.
      Furthermore, using AFM we demonstrated that the presence of LDs in the
      endothelium affected endothelial stiffness which could have pathophysiological
      significance. In summary, the results suggest that the formation of LDs in the
      endothelium involves exogenous and endogenous polyunsaturated fatty acids, and
      their relative contribution to the LD formation seems distinct for AA, EPA and
      DHA.

PMID- 29372725
TI  - Evolution of 2D tin oxides on the surface of molten tin.
AB  - The exfoliation of two dimensional (2D) oxides, established on the surface of
      specific liquid metals, has recently been introduced. One such liquid metal is
      molten tin, which forms a variety of surface 2D oxides. However, the development
      behaviour of these surface tin oxides is still unknown. Here the evolution of
      stoichiometry and thickness from single-layer SnO to highly oxidised multi-layer
      SnO2 in ambient oxygen is explored.

PMID- 29372726
TI  - First principles study of electronic transport properties in novel FeB2 flake
      based nanodevices.
AB  - First-principles calculations can provide theoretical support for the promising
      applications of innovative two-probe devices based on FeB2 flakes at different
      temperatures. Results indicate that these FeB2-based devices not only exhibit a
      prominent transport capacity and a predictable strong current, but also possess
      outstanding electrical conductivity compared with many flake-based devices.
      Devices with FeB2 flakes at temperatures not above 1000 K have advantageous
      transmission and low-voltage current because of the delocalization of electronic
      states, essentially resulting from their undeformed flake structures.
      Importantly, Fe atoms are pivotal in the electron transport of FeB2-based
      devices. The edge effect of the flakes is also analyzed. These new-type FeB2
      flakes can realize substantial value in nanoscale functional devices.

PMID- 29372727
TI  - Toward a muon-specific electronic structure theory: effective electronic Hartree
      Fock equations for muonic molecules.
AB  - An effective set of Hartree-Fock (HF) equations are derived for electrons of
      muonic systems, i.e., molecules containing a positively charged muon, conceiving
      the muon as a quantum oscillator, which are completely equivalent to the usual
      two-component HF equations used to derive stationary states of the muonic
      molecules. In these effective equations, a non-Coulombic potential is added to
      the orthodox coulomb and exchange potential energy terms, which describes the
      interaction of the muon and the electrons effectively and is optimized during the
      self-consistent field cycles. While in the two-component HF equations a muon is
      treated as a quantum particle, in the effective HF equations it is absorbed into
      the effective potential and practically transformed into an effective potential
      field experienced by electrons. The explicit form of the effective potential
      depends on the nature of muon's vibrations and is derivable from the basis set
      used to expand the muonic spatial orbital. The resulting effective Hartree-Fock
      equations are implemented computationally and used successfully, as a proof of
      concept, in a series of muonic molecules containing all atoms from the second and
      third rows of the Periodic Table. To solve the algebraic version of the equations
      muon-specific Gaussian basis sets are designed for both muon and surrounding
      electrons and it is demonstrated that the optimized exponents are quite distinct
      from those derived for the hydrogen isotopes. The developed effective HF theory
      is quite general and in principle can be used for any muonic system while it is
      the starting point for a general effective electronic structure theory that
      incorporates various types of quantum correlations into the muonic systems beyond
      the HF equations.

PMID- 29372729
TI  - Porphyrin-sensitized solar cells: systematic molecular optimization, coadsorption
      and cosensitization.
AB  - As a promising low-cost solar energy conversion technique, dye-sensitized solar
      cells have undergone spectacular development since 1991. For practical
      applications, improvement of power conversion efficiency has always been one of
      the major research topics. Porphyrins are outstanding sensitizers endowed with
      strong sunlight harvesting ability in the visible region and multiple reaction
      sites available for functionalization. However, judicious molecular design in
      consideration of light-harvest, energy levels, operational dynamics, adsorption
      geometry and suppression of back reactions is specifically required for achieving
      excellent photovoltaic performance. This feature article highlights some of the
      recently developed porphyrin sensitizers, especially focusing on the systematic
      dye structure optimization approach in combination with coadsorption and
      cosensitization methods in pursuing higher efficiencies. Herein, we expect to
      provide more insights into the structure-performance correlation and molecular
      engineering strategies in a stepwise manner.

PMID- 29372728
TI  - Ab initio and transition state theory study of the OH + HO2 -> H2O + O2(3Sigmag
      )/O2(1Deltag) reactions: yield and role of O2(1Deltag) in H2O2 decomposition and
      in combustion of H2.
AB  - Reactions of hydroxyl (OH) and hydroperoxyl (HO2) are important for governing the
      reactivity of combustion systems. We performed post-CCSD(T) ab initio
      calculations at the W3X-L//CCSD = FC/cc-pVTZ level to explore the triplet ground
      state and singlet excited-state potential energy surfaces of the OH + HO2 -> H2O
      + O2(3Sigmag-)/O2(1Deltag) reactions. Using microcanonical and multistructural
      canonical transition state theories, we calculated the rate constant for the
      triplet and singlet channels over the temperature range 200-2500 K, represented
      by k(T) = 3.08 * 1012T0.07 exp(1151/RT) + 8.00 * 1012T0.32 exp(-6896/RT) and k(T)
      = 2.14 * 106T1.65 exp(-2180/RT) in cm3 mol-1 s-1, respectively. The branching
      ratios show that the yield of singlet excited oxygen is small (<0.5% below 1000
      K). To ascertain the importance of singlet oxygen channel, our new kinetic
      information was implemented into the kinetic model for hydrogen combustion
      recently updated by Konnov (Combust. Flame, 2015, 162, 3755-3772). The updated
      kinetic model was used to perform H2O2 thermal decomposition simulations for
      comparison against shock tube experiments performed by Hong et al. (Proc.
      Combust. Inst., 2013, 34, 565-571), and to estimate flame speeds and ignition
      delay times in H2 mixtures. The simulation predicted a larger amount of
      O2(1Deltag) in H2O2 decomposition than that predicted by Konnov's original model.
      These differences in the O2(1Deltag) yield are due to the use of a higher ab
      initio level and a more sophisticated methodology to compute the rate constant
      than those used in previous studies, thereby predicting a significantly larger
      rate constant. No effect was observed on the rate of the H2O2 decomposition and
      on the flame speeds and ignition delay times of different H2-oxidizer mixtures.
      However, if the oxidizer is seeded with O3, small differences appear in the flame
      speed. Given that O2(1Deltag) is much more reactive than O2(3Sigmag-), we do not
      preclude an effect of the singlet channel of the titled reaction in other
      combustion systems, especially in systems where excited oxygen plays an important
      role.

PMID- 29372730
TI  - Inducing chemical reactivity on specific sites of a molecule using the Coulomb
      interaction exerted by a low energy electron.
AB  - Remarkable site-specificity in the resonant attachment of low energy electrons
      (LEEs) to molecular targets is proposed as an efficient method for inducing
      chemical reactivity on specific sites of molecules. The Coulomb interaction
      between the attached electron and the most polarizable molecular electrons
      localized on the attached site is the reason for site-specific chemical
      reactivity. The Coulombically induced site-specific chemical reactivity is best
      illustrated by the LEE induced chemical transformation of a weakly bound
      molecular complex into a strong covalent adduct. The chemical transformation
      occurs due to the Coulombically induced nucleophilicity on a specific molecular
      moiety in the complex. A simple strategy for inducing site-specific chemical
      reactivity using a LEE may find new avenues in chemical synthesis.

PMID- 29372731
TI  - Computational analysis of carbohydrate recognition based on hybrid QM/MM
      modeling: a case study of norovirus capsid protein in complex with Lewis antigen.
AB  - Norovirus is a major pathogen of nonbacterial acute gastroenteritis in humans and
      animals. Carbohydrate recognition between norovirus capsid proteins and Lewis
      antigens is considered to play a critical role in initiating infection of
      eukaryotic cells. In this article, we first report a detailed atomistic
      simulation study of the norovirus capsid protein in complex with the Lewis
      antigen based on ab initio QM/MM combined with MD-FEP simulations. To understand
      the mechanistic details of ligand binding, we analyzed and compared the
      carbohydrate recognition mechanism of the wild-type P domain protein with a
      mutant protein. Small structural differences between two capsid proteins are
      observed on the weak interaction site of residue 389, which is located on the
      solvent exposed surface of the P domain. To further clarify affinity differences
      in ligand binding, we directly evaluated free energy changes of the ligand
      binding process. Although the mutant protein loses its interaction energy with
      the Lewis antigen, this small amount of energy penalty is compensated for by an
      increase in the solvation stability, which is induced by structural
      reorganization at the ligand binding site on the protein surface. As a sum of
      these opposite energy components, the mutant P domain obtains a slightly enhanced
      binding affinity for the Lewis antigen. The present computational study clearly
      demonstrated that a detailed free energy balance of the interaction energy
      between the capsid protein and the surrounding aqueous solvent is the mechanistic
      basis of carbohydrate recognition in the norovirus capsid protein.

PMID- 29372732
TI  - The fold preference and thermodynamic stability of alpha-synuclein fibrils is
      encoded in the non-amyloid-beta component region.
AB  - The heterogeneity of the synucleinopathies, neurological disorders that include
      Parkinson's disease (PD), indicates that toxicity, seeding/cross-seeding ability,
      and propagation of alpha-synuclein (alphaS) assemblies depend on their distinct
      structural characteristics or "strain". To examine the molecular signature that
      encodes the aggregation seed, conformational preference, and thermodynamic
      stability of full-length alphaS fibrils, we performed molecular dynamics
      simulations on two non-amyloid-beta component (NAC) fibril structures, containing
      residues 61-95 of two distinct alphaS fibrils. We identified several discrete hot
      spots in the recognized hydrophobic core of NAC (residues 68-82) that could
      initiate the early assembly of alphaS. We show that NAC fibrils inherit the
      preferred fold of their parent alphaS fibril, but could switch conformational
      preference in two fibril mutants K80Q and E83Q under different solution
      conditions. Similar to alphaS fibrils, NAC fibrils are also sensitive to
      temperature and salt concentration. The favorable solvation free energy of NAC
      fibrils at low temperature (280 K) suggests a propensity for cold-denaturation.
      Our results indicate that the strain-dependent synucleinopathies may be partially
      imprinted in the fold-dependent thermodynamic properties of NAC fibrils,
      providing structural insights into the emerging development of anti-PD treatments
      that target the NAC region of alphaS.

PMID- 29372733
TI  - Triphenylamine based yellowish-orange light emitting organic dyes (donor-pi
      acceptor) for hybrid WLEDs and OLEDs: synthesis, characterization and theoretical
      study.
AB  - Six novel yellowish-orange light emitting dye molecules consisting of an electron
      deficient phenone (acceptor) linked to triphenylamine (donor), were designed and
      synthesized. The photophysical and electrochemical properties of the dyes were
      systematically investigated and examined using DFT calculations. All the
      synthesized dye materials have shown high quantum yields (ranging from
      0.35to0.74%). The dyes emitted intense yellowish-orange (x = 0.427, y = 0.481) to
      orange color (x = 0.511, y = 0.484) with appropriate CIE color coordinates. The
      synthesised dyes were used for generating white light by fabricating white LEDs.
      Among all hybrid white LED devices TPA-2 has shown bright white emission with CIE
      color coordinates x = 0.32, y = 0.33. Theoretical calculations have been
      performed to explore the optical, electronic, charge transport, and stability
      properties of the TPA derivatives as charge transport and emissive materials for
      organic light emitting devices (OLEDs). The results show that, all the
      derivatives are highly luminescent and their hole transport performances are more
      favourable than their electron transport performances. So these materials can be
      used as hole transport materials for OLEDs.

PMID- 29372734
TI  - A new approach to fabricate the Mn(ii)-based magnetic refrigerant through
      incorporation of a diamagnetic {LiO4} spacer.
AB  - A new 3D MOF [MnLi2(ip)2(H2O)2] (1) with a 1D heterometallic inorganic Mn(ii)
      Li(i) chain is reported. With the assistance of diamagnetic {LiO4} connectors,
      which separate the paramagnetic Mn(ii) ions and act as magnetic spacers, very
      weak magnetic interactions were obtained. Remarkably, 1 showed a significant
      magnetocaloric effect (MCE) with a large entropy change value of 30.4 J kg-1 K-1
      for DeltaH = 8 T at 2 K.

PMID- 29372736
TI  - Supercurrent and multiple Andreev reflections in micrometer-long ballistic
      graphene Josephson junctions.
AB  - Ballistic Josephson junctions are predicted to support a number of exotic physics
      processess, providing an ideal system to inject the supercurrent in the quantum
      Hall regime. Herein, we demonstrate electrical transport measurements on
      ballistic superconductor-graphene-superconductor junctions by contacting graphene
      to niobium with a junction length up to 1.5 MUm. Hexagonal boron nitride
      encapsulation and one-dimensional edge contacts guarantee high-quality graphene
      Josephson junctions with a mean free path of several micrometers and record-low
      contact resistance. Transports in normal states including the observation of
      Fabry-Perot oscillations and Sharvin resistance conclusively witness the
      ballistic propagation in the junctions. The critical current density JC is over
      one order of magnitude larger than that of the previously reported junctions.
      Away from the charge neutrality point, the ICRN product (IC is the critical
      current and RN the normal state resistance of junction) is nearly a constant,
      independent of carrier density n, which agrees well with the theory for ballistic
      Josephson junctions. Multiple Andreev reflections up to the third order are
      observed for the first time by measuring the differential resistance in the
      micrometer-long ballistic graphene Josephson junctions.

PMID- 29372735
TI  - Isolation of circulating plasma cells from blood of patients diagnosed with
      clonal plasma cell disorders using cell selection microfluidics.
AB  - Blood samples from patients with plasma cell disorders were analysed for the
      presence of circulating plasma cells (CPCs) using a microfluidic device modified
      with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a
      CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy
      of undetermined significance (MGUS), all patients with smouldering and
      symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs
      was higher in patients with symptomatic MM compared with MGUS and smouldering MM
      (p < 0.05). FISH analysis revealed the presence of chromosome 13 deletions in
      CPCs that correlated with bone marrow results. Point mutations in KRAS were
      identified, including different mutations from sub-clones derived from the same
      patient. The microfluidic assay represents a highly sensitive method for
      enumerating CPCs and allows for the cytogenetic and molecular characterization of
      CPCs.

PMID- 29372737
TI  - The effect of metal distribution on the luminescence properties of mixed
      lanthanide metal-organic frameworks.
AB  - A series of lanthanide metal-organic frameworks (MOFs) of the general formula
      [Ln(Hodip)(H2O)].nH2O (Sm, 1; Eu, 2; Gd, 3; Tb, 4; Dy, 5; Er, 6; H4odip = 5,5'
      oxydiisophthalic acid) have been prepared and shown crystallographically to have
      isostructural three-dimensional frameworks. The fluorescence emission spectra of
      the europium compound 2, which is red, and the terbium compound 4, which is
      green, show characteristic peaks for transitions involving the metal centres,
      whereas that for the gadolinium compound 3 is dominated by transitions involving
      Hodip. Using a 1 : 1 : 1 mixture of europium, gadolinium and terbium nitrates in
      the synthesis resulted in the mixed-metal MOF
      [Gd0.17Tb0.19Eu0.64(Hodip)(H2O)].nH2O 7, for which the ratio of the metal ions
      was determined using EDX spectroscopy. The fluorescence emission spectrum of 7 is
      dominated by europium emission bands reflecting the higher proportion of Eu3+
      centres and quenching of the terbium fluorescence by metal-to-metal energy
      transfer. A series of core-shell MOF materials based on the Ln(Hodip)(H2O)
      framework have been prepared in order to isolate the lanthanides in different
      domains within the crystals. The emission spectra for materials with Gd@Tb@Eu (8)
      and Tb@Eu@Gd (9) are dominated by terbium emissions, suggesting that physical
      separation from europium suppresses quenching. In contrast, the material with
      Eu@Gd@Tb (10) shows only broad ligand bands and europium emissions. This confirms
      that core-shell MOFs have different fluorescence properties to simple mixed-metal
      MOFs, demonstrating that the spatial distribution of the metals within a mixed
      lanthanide MOF affects the fluorescence behaviour.

PMID- 29372741
TI  - Correction: A tetramer micelle: the smallest aggregation number corresponding to
      the vertex number of regular polyhedra in platonic micelles.
AB  - Correction for 'A tetramer micelle: the smallest aggregation number corresponding
      to the vertex number of regular polyhedra in platonic micelles' by Shota Fujii et
      al., Soft Matter, 2018, DOI: .

PMID- 29372742
TI  - InPZnS alloy quantum dots with tris(hexylthio)phosphine as a dual anionic
      precursor.
AB  - Recently, InP-based quantum dots (QDs) have received significant attention due to
      their usefulness in display applications, and the search for good optical
      properties has led to numerous reports on the testing of reaction variables.
      However, most researchers have precluded the most important anion precursors in
      their studies, instead of focusing only on
      tris(trimethylsilyl)phosphine(P(SiMe3)3, TMS3P) precursors. Due to its
      vulnerability to moisture, TMS3P is unstable and difficult to handle. In the
      current study, a new anionic precursor, tris(hexylthio)phosphine(THTP), is
      introduced for use with InP-based QDs. Owing to its activated phosphine and
      sulfur atoms, the THTP molecule is a dual anionic precursor for both InP and ZnS
      QDs. When THTP is reacted with indium and zinc precursors, InPZnS alloy QDs can
      be fabricated. To observe the synthesis mechanism and probe the intermediate, FAB
      mass and 31P-NMR analyses were conducted, resulting in the identification of an
      intermediate of MW 504. Finally, the surface was coated with a ZnS shell to
      obtain the emission wavelength from 530 nm to 570 nm and a maximum quantum
      efficiency of 42% when a ZnI2 precursor was used.

PMID- 29372743
TI  - Dextran-coated iron oxide nanoparticle-improved therapeutic effects of human
      mesenchymal stem cells in a mouse model of Parkinson's disease.
AB  - Parkinson's disease (PD) is a prevalent neurodegenerative disease characterized
      by the loss of dopaminergic (DA) neurons. With their migration capacity toward
      the sites of diseased DA neurons in the PD brain, mesenchymal stem cells (MSCs)
      have the potential to differentiate to DA neurons for the replacement of damaged
      neurons and to secrete neurotrophic factors for the protection and regeneration
      of diseased DA neurons; therefore MSCs show promise for the treatment of PD. In
      this study, for the first time, we demonstrate that dextran-coated iron oxide
      nanoparticles (Dex-IO NPs) can improve the therapeutic efficacy of human MSCs
      (hMSCs) in a mouse model of PD induced by a local injection of 6-hydroxydopamine
      (6-OHDA). In situ examinations not only show that Dex-IO NPs can improve the
      rescue effect of hMSCs on the loss of host DA neurons but also demonstrate that
      Dex-IO NPs can promote the migration capacity of hMSCs toward lesioned DA neurons
      and induce the differentiation of hMSCs to DA-like neurons at the diseased sites.
      We prove that in vitro Dex-IO NPs can enhance the migration of hMSCs toward 6
      OHDA-damaged SH-SY5Y-derived DA-like cells, induce hMSCs to differentiate to DA
      like neurons in the conditioned media derived from 6-OHDA-damaged SH-SY5Y-derived
      DA-like cells and promote the protection/regeneration effects of hMSCs on 6-OHDA
      damaged SH-SY5Y-derived DA-like cells. We confirm the potential of MSCs for cell
      based therapy for PD. Dex-IO NPs can be used as a tool to accelerate and optimize
      MSC therapeutics for PD applicable clinically.

PMID- 29372744
TI  - Magnetic bistability of a TbPc2 submonolayer on a graphene/SiC(0001) conductive
      electrode.
AB  - The alteration of the properties of single-molecule magnets (SMMs) due to the
      interaction with metallic electrodes is detrimental to their employment in
      spintronic devices. Conversely, herein we show that the terbium(iii) bis
      phthalocyaninato complex, TbPc2, maintains its SMM behavior up to 9 K on a
      graphene/SiC(0001) substrate, making this alternative conductive layer highly
      promising for molecular spintronic applications.

PMID- 29372745
TI  - Salt-assisted synthesis of 3D open porous g-C3N4 decorated with cyano groups for
      photocatalytic hydrogen evolution.
AB  - Three-dimensional open porous graphitic carbon nitride with cyano groups (3D OPG
      C3N4-CN) has been fabricated by a facile two-step process that combines NaCl
      assisted freeze-drying with calcination. NaCl not only works as a template for
      the 3D open porous structure, but also facilitates the decomposition of g-C3N4
      around 500  degrees C to some extent. Meanwhile, a moderate amount of cyano
      groups acting as electron capture centers are introduced at the edge of the 3D
      open porous g-C3N4 during the formation process. Compared with bulk g-C3N4
      without NaCl assistance, the 3D OPG-C3N4-CN exhibits improved light absorption,
      reduced carrier recombination and more active sites. As a result, the enhanced
      hydrogen production of 3D OPG-C3N4-CN reaches up to 1590 MUmol h-1 g-1 when using
      Pt as a cocatalyst, which is about six times as much as that of the bulk g-C3N4.

PMID- 29372746
TI  - Trace level Al3+ detection in aqueous media utilizing luminescent ensembles
      comprising pyrene laced dynamic surfactant assembly.
AB  - Easily synthesizable amphiphilic probes have been designed for the detection of
      Al3+ exclusively at mesoscopic interfaces. The surface charge of the surfactant
      assemblies and the fluidity of the lipid aggregates show pronounced effects on
      the extent of Al3+ detection. Excellent sensitivity has been observed
      specifically in the presence of anionic surfactants and the lipid membranes with
      more sol-like characteristics. Moreover, a variation in the modes of Al3+
      complexation is observed on shifting from one regioisomer to another. For
      instance, the para isomer exhibits a 1 : 2 stoichiometry with the Al3+ ion, while
      for the ortho-isomer, it is a 1 : 1 interaction. Considering the excellent
      sensitivity of the probe molecule towards Al3+, the present system has been
      utilized for the estimation of soluble aluminum content in acidic soil samples as
      well as in pharmaceutical tablets. Low-cost paper strips are developed for rapid,
      on-site detection of Al3+ without involving advanced instruments or trained
      technicians. Finally, the bioimaging of Al3+ is achieved in cervical cancer
      (HeLa) cells.

PMID- 29372747
TI  - The p(O2)-T stability domain of cubic perovskite Ba0.5Sr0.5Co0.8Fe0.2O3-delta.
AB  - Cubic perovskite-type Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF) is one of the mixed
      ionic-electronic conductors with the highest oxygen permeability known to date.
      It serves as a parent material for the development of functional derivatives for
      electrochemical applications including oxygen separation membranes, solid
      electrolyte cell electrodes and electrocatalysts for the oxygen evolution
      reaction. The present study is focused on the determination of the precise
      stability boundaries of cubic perovskite BSCF employing a coulometric titration
      technique in combination with thermogravimetric analysis, X-ray and neutron
      diffraction, and molecular dynamics simulations. Both the low-p(O2) and high
      p(O2) stability boundaries at 700-950  degrees C were found to correspond to a
      fixed value of oxygen content in the perovskite lattice of 3 - delta = ~2.13 and
      ~2.515, respectively. The stability limits in this temperature range are
      expressed by the following equations: high-p(O2) boundary: log p(O2) (atm) (+/
      0.1) = -10 150/T (K) + 8.055; low-p(O2) boundary: log p(O2) (atm) (+/-0.03) = -20
      750/T (K) + 4.681. The p(O2)-T phase diagram of the BSCF system under oxidizing
      conditions is addressed in a wider temperature range and is shown to include a
      region of precipitation of a "low-temperature" phase occurring at 400-500 
      degrees C. The fraction of the low-temperature precipitate, which co-exists with
      the cubic perovskite phase and is stable up to 790-820  degrees C, increases upon
      increasing p(O2) in the range 0.21-1.0 atm.

PMID- 29372748
TI  - Correction: 3D polymer objects with electronic components interconnected via
      conformally printed electrodes.
AB  - Correction for '3D polymer objects with electronic components interconnected via
      conformally printed electrodes' by Yejin Jo, et al., Nanoscale, 2017, 9, 14798
      14803.

PMID- 29372749
TI  - Corrigendum: Inhibitor Selectivity for Cyclin-Dependent Kinase 7: A Structural,
      Thermodynamic, and Modelling Study.

PMID- 29372751
TI  - The impact of health and health insurance literacy on access to care for
      Hispanic/Latino communities.
AB  - OBJECTIVES: The aim of this study was to assess the impact of health literacy
      (HL) and health insurance literacy (HIL) on health insurance status and access to
      health care services for Spanish-speaking communities living in Massachusetts.
      METHODS: A total of 139 surveys (descriptive, knowledge-based HIL questions, and
      Short Assessment of Health Literacy in Spanish) and 30 semi-structured interviews
      were collected and analyzed using chi-square, Mann-Whitney U test, and logistic
      regression analysis. RESULTS: The majority of participants had inadequate HL
      (56%) and HIL (93%). There were differences in HL scores (t = 4.1; p < .0001)
      between the insured (M = 12.3, SD = 5.7) and uninsured (M = 7.9, SD = 6.7) and
      differences (t = 1.9; p = .05) between those with adequate HIL (M = 14.3, SD =
      4.3) and inadequate HIL (M = 10.2, SD = 6.6). Participants who were uninsured (MW
      U = 37.6; p < .0001) and who had inadequate HL (MW U = 5.2; p = .02) were more
      likely to have never accessed health care in the U.S. Participants who had never
      accessed health care were 93% less likely to be insured and those with adequate
      HL were three times more likely to be insured. CONCLUSIONS: Health literacy and
      HIL are closely associated with insurance status and access to health care for
      Spanish-speaking communities, indicating the need for further research and
      enhanced public health efforts to improve knowledge and awareness around
      navigating health care systems.

PMID- 29372750
TI  - The Role of Preterm Birth in the Association Between Opioid Maintenance Therapy
      and Neonatal Abstinence Syndrome.
AB  - BACKGROUND: Pregnant women treated with methadone as opioid maintenance therapy
      are more likely than women treated with buprenorphine to deliver preterm. Preterm
      birth is associated with less risk of neonatal abstinence syndrome (NAS). We
      sought to assess the role of preterm birth as a mediator of the relationship
      between in utero exposure to methadone and NAS compared with buprenorphine.
      METHODS: We studied 716 women receiving methadone or buprenorphine and delivering
      liveborn infants at Magee-Womens Hospital, Pittsburgh, Pennsylvania (2013-15). We
      implemented inverse probability weighted marginal structural models to isolate
      the role of preterm birth (<37 weeks' gestation). Weights accounted for
      confounding by maternal age, race, insurance, parity, delivery year, marital,
      employment, hepatitis C, and smoking status. RESULTS: Approximately 57% of the
      cohort were treated with methadone. Preterm birth was more common in methadone
      exposed pregnancies (25% versus 14%). The incidence of NAS treatment was higher
      in methadone compared with buprenorphine-exposed infants (65% vs 49%), and term
      compared with preterm births (64% vs 36%). For every 100 infants liveborn to
      mothers treated for opioid dependence, there were 13 excess cases of NAS among
      infants exposed to methadone compared with buprenorphine (adjusted risk
      difference [RD] 13.3, 95% confidence interval [CI] 5.7, 20.9). Among term births,
      this increased to 17 excess cases of NAS in methadone- compared with
      buprenorphine-exposed (RD 16.7, 95% CI 9.3, 24.0). CONCLUSION: The further
      increased risk of NAS associated with methadone use vs buprenorphine in term
      deliveries emphasises the utility of buprenorphine in clinical settings aimed at
      decreasing NAS.

PMID- 29372753
TI  - The face of tiredness in insomnia from the self-perspective: A focus on
      attentional and interpretative biases.

PMID- 29372752
TI  - Catalytic Dearomative Spirocyclization via Gold Carbene Species Derived from
      Ynamides: Efficient Synthesis of 2-Azaspiro[4.5]decan-3-ones.
AB  - An intramolecular catalytic dearomatization of phenols via gold carbene species
      proceeded to provide 2-azaspiro[4.5]decan-3-ones. The use of NHC ligand and water
      as a co-solvent was critical for achieving high reactivity. This reaction did not
      require hazardous diazo compounds as carbene sources and proceeded even under
      air. The obtained spirocyclic product could be readily transformed into a
      gabapentin derivative by hydrogenation and deprotection.

PMID- 29372755
TI  - [Preparation and evaluation of multidentate ligand-bonded silica chromatographic
      medium].
AB  - Iminodisuccinic acid (IDS), a green environment-friendly multidentate chelating
      agent, was used as a ligand to synthesize IDS-Silica stationary phase under the
      optimized conditions. The binding capacity of IDS on the stationary phase was
      measured by potentiometric titration. The chromatographic properties and metal
      chelating property on IDS-Silica column were investigated. Three standard protein
      mixtures were separated successfully with IDS-Silica column. The results showed
      that the IDS-Silica column displayed a typical cation exchange property. The
      binding characteristics of six different metal ions on IDS-Silica stationary
      phase were examined by inductively coupled plasma-atomic emission spectroscopy
      (ICP-AES). The results validated that the variation of binding capacities of
      metal ions on the stationary phase were consistent with the chelating stability
      order of the IDS-Silica column for metal ions. Compared with the other silica
      columns bonded with the three different aminocarboxyl ligands, the bonding
      amounts of Cu2+ on IDS-Silica column was the largest, which indicated that IDS
      had stronger chelating ability for metal ions. This characteristic lays the
      foundation for IDS as a good chromatographic packing used in the field of
      immobilized metal affinity chromatography (IMAC), thus probably provides an
      effective solution to reduce the leaking problem of metal ion from IMAC column
      during protein elution with one competitive agent.

PMID- 29372756
TI  - [Preparation and investigation of novel pyrrolidinium-bonded stationary phase for
      reversed-phase high-performance liquid chromatography].
AB  - A new ionic liquid-based high-performance liquid chromatography stationary phase
      is reported. A derivative of N-methyl pyrrolidinium tetrafluoroborate was
      covalently immobilized on the surface of silica particles to prepare silica-based
      N-methyl pyrrolidinium tetrafluoroborate (SilprMP BF4) stationary phase. The
      obtained ionic liquid-modified silica was evaluated and confirmed by elemental
      analysis, infrared spectroscopy, and thermogravimetric analysis. A column was
      packed with the modified particles. The retention behavior of aromatic compounds,
      alkyl benzenes, and acidic and basic compounds on the SilprMP BF4 stationary
      phase was studied under reversed-phase liquid chromatography conditions. The
      effect of the eluent pH on the separation of the acidic and basic compounds was
      also studied. The new stationary phase involves multiple retention mechanisms,
      such as electrostatic, hydrophobic, ion-dipole, and anion-exchange interactions,
      which might lead to multipurpose separation media.

PMID- 29372757
TI  - [Rapid determination of 55 fungicides in siraitia grosvenoriis by QuEChERS and
      high performance liquid chromatography-tandem mass spectrometry].
AB  - A method for the determination of 55 fungicides in siraitia grosvenoriis by
      QuEChERS and high performance liquid chromatography-tandem mass spectrometry
      (HPLC-MS/MS) was established. The samples were extracted with acetonitrile
      containing 1%(v/v) acetic acid, then dehydrated by anhydrous magnesium sulfate
      and purified by anhydrous sodium sulfate, N-propyl ethylenediamine (PSA) and C18.
      Then, 95% (v/v) acetonitrile aqueous solution (organic phase) and water (aqueous
      phase), both containing 0.005 mol/L ammonium formate and 0.01% (v/v) formic acid,
      were used as mobile phases with gradient elution. The compounds were tested by
      positive electrospray ion source (ESI+) and dynamic multiple reaction monitoring
      (DMRM) mode. Fifty-five fungicides were quantified by external standard method
      considering matrix effects. The correlation coefficients (R2) were greater than
      0.99, which indicated that the linear dependence of the 55 fungicides were good
      in the range of 1.0-100.0 MUg/kg. The LODs (S/N>3) and LOQs (S/N>10) of all the
      fungicides were 1.0 MUg/kg and 10.0 MUg/kg, respectively. The recoveries were in
      the range of 76.96%-118.45% and the relative standard deviations (RSDs) ranged
      from 3.44% to 19.63% (n=6). This method has the advantages of rapidity, accuracy
      and sensitivity for the high-throughput detection of fungicides residues in
      siraitia grosvenoriis.

PMID- 29372758
TI  - [Fast determination of pericarpium papaveris illegally added in foods by
      TurboFlow online purification-ultra performance liquid chromatography-triple
      quadrupole/linear ion trap mass spectrometry].
AB  - A fast confirmation method was developed for the determination of the six markers
      of pericarpium papaveris, morphine, codeine, narcotine, papavarine, thebaine and
      protopine in foods, by TurboFlow online purification-ultra performance liquid
      chromatography-triple quadrupole/linear ion trap mass spectrometry (TF-UPLC-QTRAP
      MS). The sample was extracted with 0.10 mol/L HCl. After the procedure of removal
      of lipid with hexane, the extraction solution was analyzed by TF-UPLC-QTRAP MS.
      The main factors influencing the purification efficiency including TurboFlow
      column, mobile phase and elution solution were optimized. The six opium alkaloids
      were detected by positive electrospray ionization tandem mass spectrometry in the
      multiple reaction monitoring-information-dependent acquisition-enhanced product
      ion (MRM-IDA-EPI) mode, and quantified by solvent standard internal standard
      method. The limits of detection were 0.05-0.5 MUg/kg and the limits of
      quantification were 0.2-2 MUg/kg for the six opium alkaloids. The recoveries were
      in the range of 81.1%-98.6% with the relative standard deviations ranging from
      2.9% to 15.7% (n=6). The method is sensitive and accurate, and has been
      successfully applied to the detection of pericarpium papaveris illegally added in
      foods.

PMID- 29372759
TI  - [Determination of six allergenic coumarin compounds in children's toys using
      hollow-fiber liquid-phase microextraction followed by ultra-performance liquid
      chromatography-tandem mass spectrometry].
AB  - A comprehensive analytical method was developed for the determination of six
      allergenic coumarin compounds (coumarin, 7-methyl coumarin, 7-methoxycoumarin, 7
      ethoxy-4-methyl coumarin, 4,6-dimethyl-8-tert-butyl coumarin and
      hexahydrocoumarin) in children's toys based on hollow-fiber liquid-phase
      microextraction (HF-LPME) followed by ultra-performance liquid chromatography
      tandem mass spectrometry (UPLC-MS/MS). HF-LPME was employed in sample
      pretreatment with the following parameters:extraction solvent of n-octanol,
      stirring rate of 700 r/min, extraction time of 50 min and amount of sodium
      chloride of 0.7 g. After chromatographic separation on an ACQUITY UPLC BEH Phenyl
      column (150 mm*2.1 mm, 1.7 MUm), the target compounds were analyzed under
      multiple reaction monitoring (MRM) mode in positive electrospray ionization mode.
      The limits of quantification (LOQs) of the six allergenic coumarin compounds were
      either 2 MUg/kg (7-ethoxy-4-methyl coumarin and 4,6-dimethyl-8-tert-butyl
      coumarin) or 10 MUg/kg (coumarin, hexahydrocoumarin, 7-methyl coumarin and 7
      methoxycoumarin). The average recoveries at different spiked levels ranged from
      70.8% to 118.9% with relative standard deviations (RSDs) of 0.19%-16.34% (n=6).
      The proposed method is accurate, sensitive, reliable, and can be applied for the
      inspection and quality control of toy products.

PMID- 29372760
TI  - [High sensitive non-derivative determination of cyclovirobuxin D by high
      performance liquid chromatography-electrochemical determination].
AB  - A high-performance liquid chromatography-electrochemical detection (HPLC-ECD)
      method was developed to determine cyclovirobuxin D (CVB-D) levels in tablets and
      human blood samples. A column with a positive charge-modified C18 stationary
      phase, C18HCE, was selected to analyze CVB-D, because it provided a sharper and
      more symmetric peak for CVB-D than conventional C18 stationary phase. Two types
      of working electrode materials, glassy carbon (GC) and boron-doped diamond (BDD),
      were evaluated. BDD was found to provide better sensitivity than GC owing to its
      lower background current and baseline noise. Utilizing the BDD electrode, C18HCE
      column, and optimized mobile phase composition, the developed HPLC-ECD method
      showed a much better sensitivity. The limit of detection and limit of
      quantification of the HPLC-ECD method for CVB-D were 0.198 and 0.297 MUg/L,
      respectively. It was approximately 12727, 11481, and 2630 times more sensitive
      than ultraviolet (UV), evaporative light scattering detection, and charged
      aerosol detection, respectively. The sensitivity of the developed HPLC-ECD method
      was comparable or even better (16.8 times) than reported mass spectrometry (MS)
      methods for the determination of CVB-D. Additionally, it offered a much wider
      linear dynamic range (up to 4 orders of magnitude, 0.297-1891 MUg/L) and was much
      less complicated than MS methods for determination of CVB-D. The developed HPLC
      ECD method can be used for determination of CVB-D at both high and low
      concentrations. Good intra-day (relative standard deviation (RSD) of peak
      area<5.08%) and inter-day (RSD of peak area<5.57%) reproducibilities of the
      developed HPLC-ECD method were obtained even for a low mass concentration (59.1
      MUg/L) sample. After the optimized parameters were acquired, this method was
      applied to the quantitative analysis of CVB-D in CVB-D tablets and human blood
      samples. With a slight modification, the current HPLC-ECD method can also be
      applied to analyze many other basic compounds including basic drugs and
      environmental pollutants.

PMID- 29372761
TI  - [Determination of patulin in fruits and jam by solid phase extraction-ultra
      performance liquid chromatography].
AB  - With magnesium silicate, silica gel, diatomite and calcium sulfate as raw
      materials, a new solid phase extraction column was prepared through a series of
      processes of grinding to ethanol homogenate, drying and packing into
      polypropylene tube. The sample was hydrolyzed by pectinase, extracted by
      acetonitrile and purified by solid phase extraction. The target compounds were
      separated on a C18 column (100 mm*2.1 mm, 1.8 MUm), using 0.8% (v/v)
      tetrahydrofuran solution as mobile phase with a flow rate of 0.5 mL/min. The
      detection wavelength was 276 nm. The effect of pectinase on extraction yield and
      purification effect of solid-phase extraction column were investigated. The
      optimum chromatographic conditions were selected. There was a good linear
      relationship between the peak heights and the mass concentrations of patulin in
      the range of 0.1 to 10 mg/L with the correlation coefficient (R2) of 1. The limit
      of detection for this method was 10.22 MUg/kg. The spiked recoveries of samples
      were 86.58%-94.84% with the relative standard deviations (RSDs) of 1.45%-2.28%.
      The results indicated that the self-made solid phase extraction column had a good
      purification efficiency, and the UPLC had a high separation efficiency. The
      method is simple, accurate and of great significance for the quality and safety
      control of fruit products.

PMID- 29372762
TI  - [Determination of iminodiacetic acid and glycine in dehydrogenation products of
      diethanolamine by pre-column derivatization and high performance liquid
      chromatography].
AB  - An analytical method was developed for the determination of iminodiacetic acid
      (IDA) and glycine (Gly), the dehydrogenation products of diethanolamine, by high
      performance liquid chromatography (HPLC) coupled with pre-column derivatization
      using p-toluenesulfonyl chloride (PTSC) as the derivatization reagent. IDA and
      Gly reacted with PTSC in the alkaline environment (pH 11) under 45C for 15 min.
      Then the derivatization products were analyzed by HPLC-MS. The separation was
      carried out on a high performance liquid chromatograph equipped with an
      ultraviolet detector. A VP-ODS column (200 mm*4.6 mm, 5 MUm) was employed using
      0.03 mol/L ammonium acetate (pH 5.5)-acetonitrile (87:13, v/v) as mobile phases
      for isocratic elution at a flow rate of 1 mL/min and detection wavelength of 235
      nm. The results showed good linearities for iminodiacetic acid of 900-2100 mg/L,
      and for glycine of 20-100 mg/L, respectively. The linear correlation coefficients
      (R2) were both greater than 0.999. The limits of detection (LODs) of IDA and Gly
      were 0.0897 mg/L and 0.0262 mg/L and the recoveries were in the range of 98.7%
      99.3% and 98.0%-99.5%, respectively. The relative standard deviations (RSDs) of
      IDA and Gly were in the range of 0.89%-1.23% and 0.95%-1.11% (n=3). The method
      has the characteristics of mild reaction conditions and high accuracy, and is
      well suitable for the determination of IDA and Gly in industrial production.

PMID- 29372763
TI  - [Determination of 18 polychlorinated biphenyls in camellia seeds by multiple
      vortex and gas chromatography-triple quadrupole mass spectrometry].
AB  - A method based on the cleaning effects of different sorbents and gas
      chromatography-triple quadrupole mass spectrometry (GC-QQQ-MS/MS) was developed
      for the determination of 18 polychlorinated biphenyls (PCBs) in camellia seeds.
      The camellia seeds were extracted with acetonitrile, salted out with sodium
      chloride, then cleaned-up by QuEChERS with anhydrous MgSO4, C18, primary
      secondary amine (PSA), and multi walled carbon nanotubes (NANO) using multiple
      vortex after the centrifugal separation, and finally analyzed by GC-QQQ-MS/MS in
      multiple reaction monitoring mode via positive electrospray ionization. All the
      18 PCBs could be completely separated with an excellent linear relationship. The
      limits of detection for the 18 PCBs were 5 MUg/kg. For all the samples, the mean
      spiked recoveries was 109.2% with relative standard deviations (RSDs) of 2.9%
      6.2% (n=3). The extraction, purification and analytical methods were developed
      and assessed. The method was successfully applied to the 48 samples from three
      main producing provinces of camellia seeds. All the 18 PCBs were not detected
      from the 48 samples.

PMID- 29372764
TI  - [Determination of three organotin pesticide residues in apples and cabbages by
      gas chromatography-electron impact/positive chemical ionization mass
      spectrometry].
AB  - A method for the simultaneous determination of fenbutatin oxide, triphenyltin and
      cyhexatin in apples and cabbages was developed by gas chromatography-mass
      spectrometry coupled with two different ionization techniques, electron impact
      (EI) ionization and positive chemical ionization (PCI). At first, the samples
      were digested by hydrobromic acid, and extracted by acetone-hexane (1:2, v/v).
      The extracts were derivatized by sodium tetraethylborate as the derivatization
      reagent, and cleaned up by the Florisil SPE columns. Finally, the samples were
      analyzed by GC-EI/MS and GC-PCI/MS in selected ion monitoring (SIM) mode. The
      results showed that good linearities were obtained with correlation coefficients
      (r2) greater than 0.997 for fenbutatin oxide in the range of 75-500 MUg/L in both
      foods, triphenyltin in the range of 50-1000 MUg/L in cabbages and 50-500 MUg/L in
      apples and cyhexatin in the range of 50-1000 MUg/L in the two foods. The accuracy
      was checked at three spiked levels (50, 100 and 200 MUg/kg) in cabbages and
      apples. The limits of detection (LODs, S/N=3) were 0.01-0.05 mg/kg (EI) and 0.01
      0.02 mg/kg (PCI), and the limits of quantifications (LOQs, S/N=10) were 0.03-0.16
      mg/kg (EI) and 0.02-0.06 mg/kg (PCI). The average recoveries ranged from 59.24%
      97.36% (apples) and 50.54%-94.54% (cabbages) in the mode of EI, and the
      corresponding values were 65.38%-95.86% and 62.56%-90.44% in the mode of PCI. The
      relative standard deviations (RSDs) were all less than 6.9% (n=6). The PCI method
      can be used to improve the accuracy in comparing with the EI, in terms of good
      selectivity and high sensitivity.

PMID- 29372765
TI  - [Determination of flavor compounds in foxtail millet wine by gas chromatography
      mass spectrometry coupled with headspace solid phase microextraction].
AB  - To comprehensively understand flavor compounds and aroma characteristics of
      foxtail millet wine, extraction conditions were optimized with 85 MUm
      polyacrylate (PA), 100 MUm polydimethylsiloxane (PDMS), 75 MUm carboxen
      (CAR)/PDMS and 50/30 MUm divinylbenzene (DVB)/CAR/PDMS fibers. The flavor
      compounds in foxtail millet wine were investigated by gas chromatography-mass
      spectrometry (GC-MS) coupled with headspace solid phase microextraction (HS
      SPME), and the odor characteristics and intensity were analyzed by odor active
      values (OAVs). The samples of 8 mL were placed in headspace vials with 1.5 g
      NaCl, then the headspace vials were heated at 60C for 40 min. Using HS-SPME with
      different fibers, a total of 55 flavor compounds were identified from the
      samples, including alcohols, esters, benzene derivatives, hydrocarbons, acids,
      aldehydes, ketones, terpenes, phenols and heterocycle compounds. The main flavor
      compounds were alcohols compounds. According to their OAVs, phenylethyl alcohol,
      styrene, 1-methyl-naphthalene, 2-methyl-naphthalene, benzaldehyde,
      benzeneacetaldehyde and 2-methoxy-phenol were established to be odor-active
      compounds. Phenylethyl alcohol and benzeneacetaldehyde were the most prominent
      odor-active compounds. PA and PDMS fibers had good extraction effect for polar
      and nonpolar compounds, respectively. CAR/PDMS and DVB/CAR/PDMS provided a
      similar compounds profile for moderate polar compounds. This research
      comprehensively determined flavor compounds of foxtail millet wine, and provided
      theoretical basis for product development and quality control.

PMID- 29372766
TI  - [Isolation and purification of seven catechin compounds from fresh tea leaves by
      semi-preparative liquid chromatography].
AB  - An effective and simple method was established to simultaneously purify seven tea
      catechins (gallocatechin (GC), epigallocatechin (EGC), catechin (C),
      epigallocatechin-3-O-gallate (EGCG), epicatechin (EC), epigallocatechin-3-O-(3-O
      methyl)-gallate (EGCG3"Me) and epicatechin-3-O-gallate (ECG)) from fresh tea
      leaves by semi-preparative high performance liquid chromatography (HPLC). Fresh
      leaves of Tieguanyin tea were successively extracted with methanol and
      chloroform. Then crude catechins were precipitated from the aqueous fraction of
      chloroform extraction by adding lead subacetate. Crude catechins were used for
      the isolation of the seven target catechin compounds by semi-preparative HPLC.
      Methanol-water and acetonitrile-water were sequentially used as mobile phases.
      After two rounds of semi-preparative HPLC, all target compounds were achieved
      with high purities (>90%). The proposed method was tested on two additional tea
      cultivars and showed similar results. This method demonstrated a simple and
      efficient strategy based on solvent extraction, ion precipitation and semi
      preparative HPLC for the preparation of multiple catechins from tea leaves.

PMID- 29372767
TI  - [Simultaneous determination of six fluorescent whitening agents in plastic and
      paper packaging materials by high performance liquid chromatography].
AB  - A novel analytical method was developed for the simultaneous determination of six
      fluorescent whitening agents (FWAs:FWA 135, FWA 184, FWA 185, FWA 199, FWA 378
      and FWA 393) in paper and plastic food packaging materials by high performance
      liquid chromatography with fluorescence detection (HPLC-FLD). The sample was
      extracted with mixed solution of chloroform and acetonitrile (3:7, v/v), then
      cleaned up by HLB solid phase extraction column. Qualitative and quantitative
      analyses were carried out by HPLC. The sample was separated on a Phenomenex C18
      column using acetonitrile and 5 mmol/L ammonium acetate aqueous solution as
      mobile phases. The results indicated that the linear range of FWA393 was 15-1500
      MUg/L and the linear ranges of the other five FWAs were 5-500 MUg/L with
      correlation coefficients greater than 0.999. The recoveries in spiked samples
      were between 80.4% and 125.0% with RSDs (n=6) of 1%-13%. Furthermore, this method
      was applied to analyze 12 samples in the market to verify the practicality of the
      method. The method showed the advantages of simplicity, high recovery and good
      precision, and is suitable for the detection of the six fluorescent whitening
      agents in food packaging materials.

PMID- 29372768
TI  - [Determination of oxygenates in methanol-to-olefin gasoline byproducts and
      methanol-to-gasoline product with solid phase extraction-gas chromatography].
AB  - Silica solid phase extraction (SPE) column was used for sample pretreatment to
      enrich the target analytes and simplify background. Due to its high efficiency,
      reliability and simplicity, the technique has been widely used in many fields.
      The byproduct gasoline of methanol-to-olefin (MTO) and the product of methanol-to
      gasoline (MTG) mainly consist of hydrocarbons along with small amounts of
      oxygenates. Trace amounts of oxygenates are hard to identify because of their
      complex hydrocarbon components. With the SPE technique, the samples were
      separated into two major classes, oxygenates and hydrocarbons. Oxygenates were
      then determined with gas chromatography-mass spectrometry (GC-MS). The elution
      conditions of the silica solid phase extraction column were optimized with the
      standard sample. Under the optimized elution conditions, the hydrocarbons were
      first eluted from the SPE column with 5 mL dichloromethane, the oxygenates were
      then eluted with 3 mL acetonitrile. The recoveries of standard samples were
      tested before and after pretreatment. The standard recoveries were 87.7%-95.3%.
      The oxygenates except methanol and ethanol were then quantified by gas
      chromatography-flame ionization detection (GC-FID) and internal standard method.
      Methanol and ethanol were then quantified by extracting characteristic ion
      chromatograms and external standard method. The results show that the oxygenates
      of MTO byproduct gasoline and MTG product mainly consist of ketones and
      aldehydes. The method improves the sensitivities of the target compounds and
      reduces the interference of the background.

PMID- 29372769
TI  - [Determination of fipronil and its metabolites in bird eggs by ultra-performance
      liquid chromatography-tandem mass spectrometry with dispersive solid phase
      extraction].
AB  - An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)
      method was developed to determine fipronil and its metabolites (fipronil
      desulfinyl, fipronil sulfone and fipronil sulfide) in bird eggs. The samples were
      extracted with acetonitrile containing 0.1%(v/v) acetic acid, and then purified
      by a mixture of anhydrous sodium sulfate, octadecyl carbon silica gel (C18-N)
      sorbent and ethylenediamine-N-propyl carbon silica gel (NH2-PSA) sorbent. The
      analysis was performed by a UPLC-MS/MS system with Shim-pack GIST C18 column (50
      mm*2.1 mm, 2 MUm). The mobile phases consisted of methanol and 1 mmol/L ammonium
      acetate aqueous solution by gradient elution, and multiple reaction monitoring
      (MRM) mode with negative electrospray ionization was used. The effect of the
      dosages of anhydrous sodium sulfate, C18-N and NH2-PSA in cleaning-up agent was
      studied. The main influence factors and analytical conditions were modified. Four
      linear calibration curves were obtained with correlation coefficients r2 >=
      0.9989. The recoveries were determined at three concentrations and ranged from
      95.09%-103.26%. The limit of quantification (LOQ) was 0.2 MUg/kg. It is suitable
      for the determination of fipronil and its metabolites in bird eggs.

PMID- 29372770
TI  - [Rapid screening of fipronil and its metabolites in egg and egg products by solid
      phase extraction-liquid chromatography-quadrupole time-of-flight mass
      spectrometry].
AB  - A method for rapid screening of fipronil and its metabolites in egg and egg
      products was developed by liquid chromatography coupled with quadrupole time-of
      flight mass spectrometry (LC-QTOF MS). The samples were extracted by acid
      acetonitrile, cleaned up by PRiME HLB SPE. The separation was performed on a
      Poroshell 120 EC C18 column (150 mm*3 mm, 2.7 MUm) with gradient elution using
      water and acetonitrile as mobile phases. The target compounds were monitored
      under negative ionization mode with electrospray ionization (ESI) source and two
      databases of accurate mass and fragment ions were created. The matrix effects in
      four kinds of egg and egg products were considered and the quantification was
      carried out by internal standard method. The results demonstrated that the linear
      ranges were from 0.1 to 5 MUg/L with good correlation coefficients (r2>0.99). The
      limits of detection (LODs, S/N>3) and limits of quantitation (LOQs, S/N>10) were
      0.2 MUg/kg and 1 MUg/kg, respectively. The recoveries of fipronil and its
      metabolites in different matrixes spiked with 1, 2 and 5 MUg/kg varied from 82.6%
      98.1%, and the relative standard deviations (RSDs) were between 3.8%-9.9% (n=6).
      The method can effectively correct the ionization suppression. It is sensitive,
      accurate and suitable for the rapid screening of fipronil, fipronil sulfide,
      fipronil sulfone and fipronil desulfinyl in egg, egg noodle, cake and mayonnaise.

PMID- 29372771
TI  - [Determination of fipronil and its metabolites in eggs and egg products with gas
      chromatography-negative chemical ionization-mass spectrometry].
AB  - A method was established for the determination of fipronil and its metabolites in
      eggs and egg products with gas chromatography-negative chemical ionization-mass
      spectrometry (GC-NCI-MS). The targets were extracted from samples with
      acetonitrile, and followed by a simple cleanup step known as dispersive solid
      phase extraction QuEChERS. The extracts were determined by GC-NCI-MS, and
      quantified by external standard method with matrix correction standard curves.
      The recoveries were in the range of 87.0% to 99.3% at four spiked levels (0.1,
      2.0, 4.0 and 20.0 MUg/kg), and all RSDs were not more than 12.7% for the four
      analytes. The linearity of the method was good between 0.005 and 0.10 mg/L, and
      all LOQs were less than 0.10 MUg/kg. So this method can be used to determine the
      residues of fipronil and its metabolites in eggs and egg products.

PMID- 29372772
TI  - [Research progress of bonded chiral stationary phases].
AB  - Chiral separation is important in biological medicine and other fields. High
      performance liquid chromatography (HPLC) is widely used in chiral separation and
      analysis for its economic, rapid and efficient characteristics. Chiral stationary
      phase (CSP) is the key to achieve chiral resolution in HPLC. Meanwhile, the key
      to preparing effective CSP is the screening of chiral selector. In recent years,
      a lot of CSPs with different chiral selectors had been prepared. Silica gel
      immobilized CSP is especially attached great attention because of its high
      solvent tolerance and stability. In this paper, the new type of CSPs prepared by
      using chiral single molecules, polysaccharides, cyclodextrins, macrocyclic
      antibiotics, crown ethers, calixarenes and alkaloids as chiral selectors are
      summarized, and the development prospect of immobilized CSPs are also discussed.

PMID- 29372773
TI  - [Preparation of organic-inorganic hybrid poly(ionic liquids) material and
      evaluation of the adsorption to dyes].
AB  - An organic-inorganic hybrid poly(ionic liquids) material was prepared by using
      allyl triethoxysilane and 1-vinyl-3-octyl imidazolium bromide ionic liquids via
      combining free radical polymerization with sol-gel process. The prepared hybrid
      poly(ionic liquids) material was characterized by infrared spectroscopy and
      scanning electron microscopy. The adsorption properties of the prepared material
      to common dyes such as tartrazine, sunset yellow, amaranth and allura red were
      investigated. The results showed that the prepared poly(ionic liquids) material
      had excellent adsorption properties to sunset yellow and allura red. The
      adsorption capacities were 29.20 and 86.17 mg/g, respectively. When the
      adsorption time was 5 min, the material showed a fast adsorption rate to allura
      red and sunset yellow, which were 87.5% and 72.8% of the balance adsorption
      capacities, respectively.

PMID- 29372774
TI  - [Confirmation and analysis of the metabolites of pentachlorophenol in loaches
      using ultra-performance liquid chromatography-high resolution mass spectrometry].
AB  - A method for the characterization of the metabolite pentachlorophenol hydrogen
      sulfate (PCP-SO3H) of pentachlorophenol (PCP) in loaches was developed based on
      ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC
      HRMS). The loach samples exposed in low concentration of PCP solution were
      firstly crushed, then extracted by acetonitrile-water solution (70:30, v/v)
      containing 8% (v/v) triethylamine and purified by mixed anion exchange solid
      phase extraction (SPE) cartridges. The chromatographic separation was carried out
      on a Waters ACQUITY BEH C18 column (100 mm*2.1 mm, 1.7 MUm). The qualitative
      analysis of the metabolites of PCP was operated in a negative electrospray ion
      mode (ESI-) under full mass-data dependent MS2 (full mass-ddMS2) mode, and the
      data of quasi-molecular ion, isotope ions, and MS2 fragmentation ions of
      metabolites were obtained. The results revealed that the sulfonation was the main
      metabolic pathway for PCP in loaches, not the hydroxylation or glucuronate
      pathway. And the metabolite was found to be PCP-SO3H. Besides, with the increase
      of exposure time in PCP solution, the concentration of metabolite PCP-SO3H
      firstly increased; when the exposure time was up to 36 h, the concentration of
      metabolite in loach reached a maximum value; and then extending the exposure
      time, the concentration of PCP-SO3H gradually decreased. When the exposure time
      was up to 120 h, the concentration of PCP-SO3H in loaches reached a lowest value,
      and no significant change occurred for further time. The developed UPLC-HRMS
      method in this study could be used for the investigation of the metabolism of PCP
      in living beings.

PMID- 29372775
TI  - [Determination of hydroxyproline in liver tissue by hydrophilic interaction
      chromatography-quadrupole/electrostatic field orbitrap high resolution mass
      spectrometry].
AB  - A method for the determination of hydroxyproline (Hyp) in liver tissue of mice by
      hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap
      high resolution mass spectrometry (HILIC-HRMS) was developed. The liver tissue
      samples of normal mice and liver fibrosis mice induced by carbon tetrachloride
      were hydrolyzed by concentrated hydrochloric acid. After filtrated and diluted by
      solution, the diluent was separated on an Hypersil GOLD HILIC column (100 mm*2.1
      mm, 3 MUm). Water-acetonitrile (28:72, v/v)were used as the mobile phases with
      isocratic elution. Finally, the target analytes were detected in positive model
      by HRMS equipped with an electrospray ionization source. The linear range of
      hydroxyproline was from 0.78 to 100.00 MUg/L with the correlation coefficient
      (R2) of 0.9983. The limit of quantification was 0.78 MUg/L. By detecting the
      spiked samples, the recoveries were in the range of 97.4%-100.9% with the
      relative standard deviations (RSDs) between 1.4% and 2.0%. In addition,
      comparison of the measurement results by this method and the chloramine T method
      was proceeded. It was found that the linear correlation between the two methods
      was very good, and the Pearson correlation coefficient was 0.927. And this method
      had simpler operation procedure and higher accuracy than chloramine T method.
      This method can be used for the quick determination of hydroxyproline in liver
      tissue samples.

PMID- 29372776
TI  - [Determination of 21 illegally added chemical drugs in health foods using ultra
      performance liquid chromatography-tandem mass spectrometry coupled with
      QuEChERS].
AB  - A method for the simultaneous determination of 21 illegally added chemical drugs
      in improving sleep and immunity health foods using ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed. Oral liquid
      and health wine samples were shaken with acetonitrile and acetonitrile-water
      formic acid (60:39:1, v/v/v), respectively, then purified by QuEChERS method. The
      extracts were separated on an Acquity UPLCTM BEH C18 column (50 mm*2.1 mm, 1.7
      MUm) with gradient elution of acetonitrile and 2 mmol/L ammonium acetate solution
      containing 0.1% (v/v) formic acid as mobile phases. The electrospray ionization
      in positive ion mode was used for analysis in multiple reaction monitoring (MRM)
      mode. The results showed that the target drugs had a good linear relationship in
      the range of 1-100 MUg/L with the correlation coefficients (R2) >= 0.992. The
      limits of detection (LODs) and limits of quantification (LOQs) were 0.07-3.41
      MUg/kg and 0.22-11.36 MUg/kg, respectively. The average recoveries of the 21
      chemical drugs in oral liquid and health wine were in the range of 61.4%-116.5%
      and 67.4%-98.4% with the relative standard deviations (RSDs) of 0.2%-13.4% and
      0.2%-11.8%, respectively. The developed method is sensitive and reliable. It has
      been successfully used for the detection of illegally added chemical drugs in
      real samples.

PMID- 29372777
TI  - [Determination of 64 veterinary drug residues in aquatic products by ultra-high
      performance liquid chromatography-quadrupole/electrostatic field orbitrap high
      resolution mass spectrometry].
AB  - A method has been developed for the simultaneous determination of 64 veterinary
      drugs in aquatic products using ultra-high performance liquid chromatography
      quadrupole/electrostatic field orbitrap high-resolution mass spectrometry. The
      samples were extracted with an acetonitrile/water mixture (80/20, v/v), cleaned
      up by normal hexane saturated with acetonitrile and primary secondary amine (PSA)
      adsorbent, quantified with external standard method. The drugs were analyzed in
      full scan/data dependent mass spectrum 2 (Full MS/ddMS2) Top 1 mode. The
      calibration curves of the 64 drugs were linear with the correlation coefficients
      more than 0. 9967. The average recoveries of the 64 analytes ranged from 56.2% to
      124.6%, and the relative standard deviations (RSDs) were 1.3%-29.8% in the three
      kinds of matrixes (fish, shrimp and shell) at three levels. The limits of
      quantification were 0.2-10 MUg/kg. The method is simple, rapid, sensitive,
      reliable and suitable for the screening of residues in aquatic products.

PMID- 29372778
TI  - [Simultaneous determination of seven avermectin residues in aquatic products by
      modified QuEChERS combined with high-performance liquid chromatography-tandem
      mass spectrometry].
AB  - A method was established for the simultaneous determination of seven avermectin
      (AVMs) residues, such as avermectin, ivermectin, doramectin, selamectin,
      eprinomectin, moxidectin and emamectin, in aquatic products using modified
      QuEChERS and high-performance liquid chromatography -tandem mass spectrometry
      (HPLC-MS/MS). The samples were extracted with 0.2% (v/v) ammoniate acetonitrile,
      and then 3 g of anhydrous magnesium sulfate and 2 g of anhydrous sodium sulfate
      were added to remove moisture and precipitate proteins. The samples were purified
      with 100 mg of C18 and 500 mg of anhydrous magnesium sulfate. The mobile phases
      comprised of acetonitrile (containing 0.1% (v/v) formic acid and 5 mmol/L
      ammonium acetate) and water (containing 0.1% (v/v) formic acid and 5 mmol/L
      ammonium acetate). The prepared samples were separated on a Varian Pursuit ULTRA
      C8 column (100 mm*2.0 mm, 2.8 MUm) and determined using heated electrospray
      ionization (HESI) in the positive ion multiple reaction monitoring (MRM) mode.
      The analytes were quantified using external standard with the matrix-matched
      standard calibration curve method. The results showed that the solvent and matrix
      matched standard curves for avermectin, ivermectin, doramectin, selamectin,
      eprinomectin and moxidectin in the range of 2-200 MUg/L and for emamectin in the
      range of 0.2-20 MUg/L were all linear, and the correlation coefficients (r) were
      >= 0.9972. The recoveries were 71.6%-112.8% with the relative standard deviations
      in the range of 4.7%-13.1%. The limits of quantification (LOQs) for avermectin,
      ivermectin, doramectin, selamectin, eprinomectin and moxidectin were all 5 MUg/kg
      and for emamectin was 0.25 MUg/kg. The present method is simple, repeatable, and
      suitable for the simultaneous determination of the residues of the seven
      avermectins in aquatic products.

PMID- 29372779
TI  - [Simultaneous rapid determination of 12 microcystins and one nodularin in water
      by direct injection-ultra performance liquid chromatography-triple quadrupole
      mass spectrometry].
AB  - A rapid method was developed for the simultaneous determination of 12
      microcystins (MCs) and one nodularin (NOD) in water by direct injection-ultra
      performance liquid chromatography-triple quadrupole mass spectrometry (UPLC
      MS/MS). The water samples were first diluted with equal volume of methanol, and
      then filtered through polyether sulfone (PES) syringe filter. The filtrates were
      directly injected into the UPLC system. The separation of the analytes was
      carried out on an ACQUITY UPLC BEH 300 C18 column (100 mm*2.1 mm, 1.7 MUm) with
      gradient elution using mobile phases of acetonitrile containing 0.1% (v/v) formic
      acid and 0.2% (v/v) formic acid aqueous solution. The 12 microcystins and one
      nodularin were detected by positive electrospray ionization in the multiple
      reaction monitoring (MRM) mode, and quantified by standard solvent external
      standard method. The limits of detection were 0.03-0.1 MUg/L and the limits of
      quantification were 0.1-0.3 MUg/L. The recoveries were in the range of 79.5%-123%
      with the relative standard deviations ranging from 1.0% to 20% (n=6). The method
      is simple, sensitive and accurate, and has been successfully applied to the
      detection of the 13 kinds of algae toxins in water.

PMID- 29372780
TI  - [Determination and identification of acrylamide residues in poly-acrylamide by
      ultra-performance liquid chromatography-quadrupole electrostatic field orbitrap
      high-resolution mass spectrometry].
AB  - A new method for the direct determination of acrylamide residues in poly
      acrylamide (PAM) by ultra-performance liquid chromatography (UPLC)-quadrupole
      electrostatic field orbitrap high-resolution mass spectrometry with the Hypercarb
      column was developed. With being diluted by water, the PAM sample was dissolved
      well by high-speed stirring. After filtering through a 0.22 MUm aqueous phase
      microporous membrane, the sample was analyzed by high-resolution mass
      spectrometry directly. Chromatographic analysis was carried out using a Hypercarb
      column, distilled water and methanol applied as the mobile phases. In addition,
      the column temperature was strictly set at 20C. The sample was determined in the
      mode of parallel reaction monitoring (PRM). Accurate mass-to-charge ratio
      extraction of the target compound ion and its fragment ion were utilized with
      elemental composition analysis and isotope distribution of the fragment ion to
      further improve the accuracy of qualitative and quantitative analysis. Meanwhile,
      the fragmentation pattern of acrylamide was acquired. The calibration curve
      showed a good linearity in the range of 2-50 MUg/L with the correlation
      coefficient of 0.9998. The limit of detection (LOD) was 1.5 MUg/kg, satisfying
      the detection demands. The recoveries of the acrylamide were in the range of
      101.3%-107.1%. The relative standard deviations (RSD) were 3.1%-4.1%. The
      applications indicated that the mass percentages of AM in PAM were in the range
      of 0-0.43%. The proposed method is easy, fast, sensitive and suitable for the
      determination and confirmation of acrylamide residues in PAM.

PMID- 29372781
TI  - [Determination of total phthalates in perfume and their exposure assessment].
AB  - A novel method for rapid screening of phthalates (PAEs) in perfumes was
      developed. The PAEs were hydrolyzed to phthalic acid (PA), and the PA in the
      acidified solution was extracted with tributyl phosphate (TBP) which was detected
      by high performance liquid chromatography-diode array detection (HPLC-DAD).
      Meanwhile exposure dose to PAEs was estimated by the percentage of a topically
      applied dose that permeates the skin. The parameters such as the concentration
      and volume of KOH, the volume of ethanol, hydrolysis time and temperature were
      employed to evaluate the hydrolysis efficiency of PAEs. The optimized hydrolysis
      conditions were 10 mL of 4 mol/L KOH, and 1 mL of ethanol at 80C for 20 min. The
      linear range of phthalic acid was 3-240 MUmol/L with a good correlation
      coefficient (R2=0.9991). The limits of detection (LOD) and quantification (LOQ)
      were 4.6 MUmol/kg and 5.9 MUmol/kg, respectively. The recoveries varied from
      83.4% to 92.7% with relative standard deviations equal to or lower than
      6.8%(n=5). A total of 35 perfume samples were determined, and the contents of
      total PAEs were found in the range of < LOD-77.738 mmol/kg, and the max exposure
      dose to PAEs for female adults was 0.4742 MUg/(kg.d) through use of perfumes. The
      method is simple and reliable, and has a wide range of applicability. It can be
      used as a new choice for the detection of PAEs in perfume.

PMID- 29372782
TI  - [Simultaneous determination of three benzimidazole fungicides in fruits and
      vegetables by capillary electrophoresis based on bacterial cellulose].
AB  - A simple and rapid capillary electrophoresis (CE) method was developed for the
      determination of trace thiophanate-methyl, carbendazim and benomyl in fruits and
      vegetables. Herein, bacterial cellulose (BC) was used as additive in running
      buffer to improve the separation efficiency. CE experimental parameters such as
      detection wavelength, concentration and pH of the running buffer, separation
      voltage as well as the contents of BC in running buffer were systematically
      investigated. Under the optimized conditions, three benzimidazole fungicides
      could be accurate quantified in 8 min using H3BO3/Na2B4O7 (4 mmol/L, pH 9.0)
      containing 0.3% (mass fraction) BC for background electrolyte, 15 kV for the
      separation voltage, 25C for the column temperature and 275 nm for detection
      wavelength. Good linearities for the three benzimidazole fungicides were obtained
      with correlation coefficients (r2) >= 0.997. The limits of detection (LODs) of
      the three benzimidazole fungicides were between 5.0 and 10.0 MUg/L. The relative
      standard deviations (RSDs, n=5) of inter-day were 0.82%-1.0% for retention times
      and 2.4%-2.9% for peak areas. The proposed method was further applied to
      determine the residues of the three benzimidazole fungicides in fruits and
      vegetables. The recoveries were in the range of 93.5%-103.0% with RSDs no more
      than 8.0%. These results indicated that the proposed method can serve as an
      efficient tool for the simultaneous determination of the three benzimidazole
      fungicides in fruits and vegetables.

PMID- 29372783
TI  - [Analysis on metabolites with small molecule of serum in bone marrow suppression
      model mice with metabolomics method].
AB  - Bone marrow suppression is a common symptom in patients with malignant tumor
      after chemotherapy. Studying the changes of metabolites caused by bone marrow
      depression can provide insights for the diagnosis of bone marrow suppression
      disease and for the development of drug therapy. Male BalB/C mice were injected
      with cyclophosphamide to establish a bone marrow suppression model. Gas
      chromatography-mass spectrometry (GC-MS) with fingerprinting was used to analyze
      the normal and model mice blood metabolites. Principal component analysis and
      orthogonal to partial least squares discriminant analysis (OPLS-DA) on
      metabolomics for data multidimensional statistical analysis was also used.
      Compared to the normal group in terms of the metabolic profile of bone marrow
      suppression mice, there were 15 endogenous metabolites in mouse plasma, nine of
      which were statistically significantly different, including glucose-1-phosphate,
      4-nitrophenol, acetanilide, cortisone, nicotinamide, loganin, caffeic acid,
      linoleic acid and oleic acid (P<0.05). These results indicate that metabolite can
      be used as an important marker in bone marrow suppression, which can help to
      reveal the pathogenesis of bone marrow suppression induced by chemotherapy and
      determine the disease development stage and the effectiveness of follow-up
      treatment.

PMID- 29372784
TI  - [Determination of six amide herbicide residues in soil by QuEChERS-gas
      chromatography-mass spectrometry].
AB  - A method was developed for the determination of six amide herbicides, such as
      acetochlor, alachlor, metolachlor, metazachlor, butachlor and pretilachlor, by
      QuEChERS-gas chromatography-mass spectrometry. The soil samples were extracted by
      10 mL acetonitrile, 10 mL deionized water and 4 g sodium chloride, then purified
      with 50 mg N-propyl ethylenediamine (PSA), 50 mg C18, 10 mg graphitized carbon
      black (GCB) and 100 mg MgSO4. Low-polar silica capillary column HP-5MS was used.
      The extracts were detected by electron impact ionization (EI) source in the
      selected ion monitoring (SIM) mode. The results showed that good linearities were
      obtained with the mass concentrations of the six amide herbicides in the range of
      0.01-1.00 mg/L, and their correlation coefficients ranged from 0.9996 to 1.0000.
      Under the condition of adding contents of 0.025, 0.10 and 0.50 mg/kg, the average
      recoveries of the six amide herbicides ranged from 92.0% to 108%, and the
      relative standard deviations were 1.64%-8.25%. The limits of detection (LODs)
      were 0.002-0.006 mg/kg and the limits of quantification (LOQs) were 0.005-0.02
      mg/kg. Comparing with the gas chromatography-electron capture detection (GC-ECD)
      which used to detect the amide herbicides, this method can improve the anti
      interference ability, and get better separation of the six amide herbicides. The
      method has the advantages of simplicity, rapidity, and application value.

PMID- 29372785
TI  - [The miRNA aberrant expression dependence on DNA methylation in HeLa cells
      treated with mitomycin C].
AB  - The dependence of expression of miRNAs and their precursors (pre-miRNAs) on the
      DNA methylation level in HeLa cells 8 days after mitomycin C treatment was
      studied. A massive parallel DNA sequencing method was applied to analyze miRNA
      expression. 5-Azacytidine (DNA methylation inhibitor) was added to the medium 6
      days after mutagenic agent exposure. The results indicated that the change in
      expression for some mature miRNAs (39 of 61) was accompanied by the change in the
      expression of their pre-miRNAs, while there were no significant changes in the
      expression of pre-miRNA for other mature miRNAs (22 of 61). The aberrant
      expression was maintained by 8 of 61 mature miRNAs and 6 of 55 pre-miRNAs in the
      induced HeLa cells after 5-azacytidine treatment. In addition, the expression of
      more than 90% of miRNAs, which indicated a significant change in expression after
      mitomycin C treatment, does not depend or depends slightly on the DNA methylation
      level in HeLa cells without mitomycin C treatment. The results suggest that
      mitomycin C induces aberrant DNA methylation which affects maintenance of changes
      in the miRNA expression in cell generations after mutagen treatment.

PMID- 29372786
TI  - [The length of chromatin loops in meiotic prophase I of warm-blooded vertebrates
      depends on the DNA compositional organization].
AB  - In meiotic prophase I, chromatin fibrils attached to the lateral elements of the
      synaptonemal complexes (SC) form loops. SCAR DNA (synaptonemal complex associated
      regions of DNA) is a family of genomic DNA tightly associated with the SC and
      located at the chromatin loop basements. Using the hybridization technique, it
      was demonstrated that localization of SCAR DNA was evolutionarily conserved in
      the isochore compositional fractions of the three examined genomes of warm
      blooded vertebrates-human, chicken, and golden hamster. The introduction of the
      concept of the comparative loops (CL) of DNA that form of chromatin attach to SC
      in the isochore compositional fractions provided the calculation of their length.
      An inverse proportional relationship between the length of CL DNA and the GC
      level in the isochore compartments of the studied warm-blooded vertebrate genomes
      was revealed. An exception was the GCpoorest L1 isochore family. For different
      compositional isochores of the human and chicken genomes, the number of genes in
      the CL DNA was evaluated. A model of the formation of GC-rich isochores in
      vertebrate genomes, according to which there was not only an increase in the GC
      level but also the elimination of functionally insignificant noncoding DNA
      regions, as well as joining of isochores decreasing in size, was suggested.

PMID- 29372787
TI  - [Nucleotide sequence and structural analysis of cryptic plasmid pBL90 from
      Brevibacterium lactofermentum].
AB  - The nucleotide sequence of cryptic plasmid (designated as pBL90) detected in the
      cells of Brevibacterium lactofermentum DSM 1412 was determined. The length of
      plasmid DNA is 67826 bp. Comparison of the nucleotide sequence of pBL90 with
      known plasmid sequences showed no long regions of significant homology. Computer
      analysis of the plasmid DNA revealed 29 open reading frames (ORFs). The amino
      acid sequences of 15 ORFs (approximately 25% of plasmid length) have a high
      (>70%) level of identity to proteins from different plasmids of Corynebacterium
      representatives, including replicative proteins. Unusual in pBL90 is the presence
      of replicative genes from two different families and types of replication.

PMID- 29372788
TI  - [Induced expression of Serratia marcescens ribonuclease III gene in transgenic
      Nicotiana tabacum L. cv. SR1 tobacco plants].
AB  - Transgenic Nicotiana tabacum L. cv. SR1 plants, characterized by an increase in
      the level of dsRNA-specific hydrolytic activity after induction by wounding, were
      obtained. The Solanum lycopersicum anionic peroxidase gene promoter (new for
      plant genetic engineering) was for the first time used for the induced expression
      of the target Serratia marcescens RNase III gene. Upon infection with the tobacco
      mosaic virus (TMV), the transgenic plants of the obtained lines did not differ
      significantly from the control group in the level of TMV capsid protein
      accumulation. In general, no delay in the development of the infection symptoms
      was observed in transgenic plants as compared with the control group. The
      obtained transgenic plants represent a new model for the study of the biological
      role of endoribonucleases from the RNase III family, including in molecular
      mechanisms of resistance to pathogens.

PMID- 29372789
TI  - [Genetic diversity and differentiation of Siberian spruce populations at nuclear
      microsatellite loci].
AB  - The results of the study of 21 populations of Siberian spruce (Picea obovata
      Ledeb.) from different parts of the species natural range by microsatellite (SSR)
      analysis of nuclear DNA are presented. Using nine loci developed for Picea abies
      (L.) Karst. and Picea glauca (Moench) Voss and detecting variation in Picea
      obovata, the parameters of intra- and interpopulation genetic diversity, as well
      as the degree of population differentiation, were determined. It was demonstrated
      that the population of Siberian spruce in the study was characterized by a
      relatively high average level of intrapopulation variability (H o = 0.408; H e =
      0.423) and low interpopulation differentiation (F st = 0.048, P = 0.001) at this
      class of DNA markers. The genetic distance between populations ranged from 0.009
      to 0.167, averaging 0.039. The isolated Magadan population, located in the
      extreme Northeast of Russia at a considerable distance from the main species
      range and characterized by the lowest genetic diversity among the studied
      populations, was maximally differentiated from the rest of the spruce
      populations. In addition, the steppe Ubukun population from Buryatia and the
      population from the Bogd Khan Uul Biosphere Reserve, Mongolia, were considerably
      different in the genetic structure from most populations of Siberian spruce,
      although to a lesser extent than the Magadan population. These findings are
      consistent with the results of previous studies of this species carried out using
      allozyme and microsatellite loci of chloroplast DNA and point to the prospects of
      using nuclear microsatellites as DNA markers to analyze the population genetic
      structure of Siberian spruce.

PMID- 29372790
TI  - [SSR polymorphism of modern cultivars and autochthonous forms of the pear tree
      from North Caucasus].
AB  - Genetic similarity and relatedness within the set of pear genotypes including
      autochthonous Circassian cultivars from North Caucasus, European cultivars,
      accessions of Pyrus caucasica Fed., and modern Russian cultivars were estimated
      on the basis of analysis of SSR loci. The level of polymorphism for the studied
      loci varied from 11 to 15 alleles per locus in the set of 29 samples of pears. A
      higher level of allelic polymorphism of SSR loci was revealed for a set of P.
      caucasica samples in comparison with modern cultivated cultivars: from 9 to 12
      alleles for P. caucasica and from 6 to 8 alleles for modern cultivars. Specific
      alleles for the mentioned groups of pears were identified. UPGMA clustering
      revealed two distinct groups: one includes P. caucasica accessions and
      autochthonous Caucasian cultivars and the other group includes all cultivated
      European and Russian pear cultivar. The results support the hypothesis of an
      isolated gene pool formation of autochthonous pear cultivars of the North
      Caucasus and their probable origin from the wild P. caucasica.

PMID- 29372791
TI  - [Expression of the stilbene synthase genes in the needles of spruce Picea
      jezoensis].
AB  - Stilbenes are valuable plant phytoalexins, the biosynthesis of which is
      characteristic of different groups of phylogenetically unrelated plants. It is
      believed that all the stilbenes are the derivatives of resveratrol (3,5,4'
      trihydroxy-trans-stilbene) or compounds close to it (pinosylvin or piceatannol).
      The last stage of the resveratrol biosynthesis takes place with the involvement
      of stilbene synthase or resveratrol synthase (STS). The family Pinaceae is
      characterized by the presence of the derivatives of pinosylvin (genus Pinus) and
      piceatannol (genus Picea), the biosynthetic pathways of which are scarcely
      examined. Previously, in different species of the genus Picea, only two stilbene
      synthase genes were described. On the basis of RNA isolated from the needles of
      spruce Picea jezoensis, the full-length cDNAs of the four stilbene synthase
      genes, PjSTS1a, PjSTS1b, PjSTS2, and PjSTS3, were obtained. Then, using the clone
      frequency analysis and real-time PCR, expression of the PjSTS1a, PjSTS1b, PjSTS2,
      and PjSTS3 genes was examined in the needles of P. jezoensis accessions of
      different age and sampled in different seasons (spring, summer, autumn, winter).
      Among the analyzed transcripts, the PjSTS1a and PjSTS1b genes were the most
      frequent, indicating their higher level of expression compared to other STS
      genes. The highest level of PjSTS1a and PjSTS1b expression was observed in
      autumn, while the level of PjSTS2 and PjSTS3 expression was the highest in spring
      and winter. Moreover, the highest PjSTS expression was detected in the young
      tissues of P. jezoensis in autumn, which may indicate a higher level of stilbene
      biosynthesis in these tissues.

PMID- 29372792
TI  - [Phylogeny of firs (genus Abies, Pinaceae) based on multilocus nuclear markers
      (AFLP)].
AB  - To study the phylogenetic relationships, evolutionary history, and molecular
      systematics of firs (genus Abies), the phylogenetic reconstruction, based on
      nuclear multilocus markers-amplified fragment length polymorphism (AFLP)-was
      conducted. Using seven combinations of selective primers, 84 samples of 39 taxa
      were genotyped for 553 polymorphic AFLP loci. A comparison with our earlier
      chloroplast and mitochondrial phylogenies of the genus (in 2014) shows that the
      nuclear phylogeny generally is more congruent to the chloroplast tree. Most of
      the clades resolved by the chloroplast phylogeny were supported also in the AFLP
      tree. Employing the nuclear DNA-based tree, we revealed the presence of new
      groups and the differences in the topology of several clades. AFLP confirmed the
      monophyly of Asian species of section Balsamea and their sister position in
      relation to the American group of species of this section. As shown by the tree
      of chloroplast DNA, Asian species of section Balsamea do not form a monophyletic
      group, but belong to the clade comprising the majority of Asian species.
      Phylogenetically mitochondrial DNA data to a large extent are not congruent to
      the nuclear and chloroplast DNA trees, and are more in line with geographical
      distribution of species. Conflicts between nuclear and cytoplasmic phylogeny were
      analyzed. Taking them into account, we consider the hypothesis of a hybrid origin
      of particular groups of firs, including ancient hybridization in section
      Balsamea. A comparison of molecular data with traditional taxonomy of the genus
      is discussed.

PMID- 29372793
TI  - [Genes encoding hevein-like antimicrobial peptides WAMPs: Expression in response
      to phytohormones and environmental factors].
AB  - We investigated the role of genes of hevein-like antimicrobial peptides of the
      WAMP family in the protection of wheat plants against biotic and abiotic stress.
      The semiquantitative RT-PCR method was used to examine the expression of wamp
      genes in wheat seedlings in response to infection by pathogens and exposure to
      phytohormones and ions of a heavy metal ion-cadmium. We discovered that wheat
      germ contamination by harmful fungi significantly increases expression of genes
      of the wamp family, and the primary transcript is wamp-2. We determined that
      salicylic acid, rather than methyl jasmonate, induces expression of genes of the
      wamp family. We showed that abiotic stress induced by cadmium ions inhibits
      expression of wamp genes in the roots with no effect on their expression in
      shoots. The results support the protective role of wamp genes in the response of
      wheat plants to infections by pathogens. In turn, the resistance to abiotic
      stress induced by cadmium ions does not appear to be associated with expression
      of genes of the wamp family.

PMID- 29372794
TI  - [Metaphase and meiotic chromosomes, synaptonemal complexes (SC) of the lizard
      Zootoca vivipara].
AB  - Somatic mitotic and meiotic chromosomes at the pachytene and at the metaphase I
      of the males of the viviparous lizard, Zootoca vivipara (Lichtenstein, 1823),
      from northwestern Russia, belonging to the Russian form of Z. v. vivipara, are
      examined. The spreading of synaptonemal complexes (SC) of their chromosomes are
      obtained and analyzed for the first time. Eighteen SC are observed, including SC
      of the Z1Z1 (pairs 5 or 6) and the Z2Z2 (pair 13) sex chromosomes.
      Characteristics of SC are compared with the number and the shape of bivalents and
      with those of the karyotype structure. In the studied Russian form of Z. v.
      vivipara, the length ratios of bivalents correlate with that of mitotic
      chromosomes (2n = 36); however, some specificity in the morphology of SC of the
      Z1Z1 sex chromosomes is reported in this article.

PMID- 29372795
TI  - [The analysis of association between type 2 diabetes and polymorphic markers in
      the CDKAL1 gene and in the HHEX/IDE locus].
AB  - The increase in diabetes was noted at the turn of the 21st century. Patients with
      type 2 diabetes (T2DM) make up the majority of patients. Diabetes is a
      multifactorial disease. It arises from adverse effects of environmental factors
      on the body of genetically susceptible peoples. According to modern concepts,
      T2DM is a polygenic disease. Each of the involved genes contributes to the risk
      of developing of this disease. In our study, the association between polymorphic
      genetic markers rs7756992, rs9465871, rs7754840, and rs10946398 in the CDKAL1
      gene and rs1111875 in the HHEX/IDE locus and T2DM in the Russian population were
      studied. Four hundred forty patients with type 2 diabetes and 264 healthy
      individuals without any signs of the disease were examined. The comparative
      analysis of distribution of genotypes and allele frequencies points to an
      association between polymorphic genetic markers rs7756992, rs9465871, and
      rs10946398 in the CDKAL1 gene and this disease. For the other polymorphic genetic
      markers (rs7754840 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus), no
      statistically significant associations are found. On the basis of these data, we
      can conclude that the CDKAL1 gene is associated with development of T2DM. For the
      HHEX/IDE locus, such an association is absent.

PMID- 29372796
TI  - [A simple and effective method for assessing chromatin diminution values in
      copepods using qPCR].
AB  - The value of chromatin diminution (CD) in different species of freshwater
      cyclopoid copepods can differ significantly. The biological and evolutionary
      roles of these differences remain unclear. To expand the knowledge on CD
      distribution and magnitude in this group of copepods, a quick method for its
      evaluation was required. This study proposes a simple approach for CD assessment
      in copepods using quantitative realtime PCR (qPCR). The magnitude of changes in
      the genome size was assessed by comparing fluorescence curves of qPCR fragments
      of target genes for pre- and post-diminution materials. The method was tested on
      four cyclopoid copepods species. In Cyclops kolensis, CD was assessed as 95.3 +/-
      1.2; in Acanthocyclops vernalis it was assessed at 94.6 +/- 0.8%; at C. insignis,
      it was 82.3 +/- 5.2%; and for the first time, CD was found in Megacyclops viridis
      at 91.1 +/- 2.6%. The advantages of our approach are its rapidity, simplicity and
      minimal requirements of materials studied.

PMID- 29372797
TI  - [Insulators can disrupt weak transcription derived from the white gene enhancer
      in Drosophila transgenic lines].
AB  - Increasing evidence suggests that noncoding RNA transcribed from the enhancers
      play an important role in the regulation of gene transcription. Insulators are
      the regulatory elements that limit the activity of enhancers and form independent
      transcriptional domains. Using a transgenic lines, we show that the Fab-7
      insulator of the bithorax complex and the MDG4 (gypsy) insulator are able to
      disrupt weak transcription derived from the enhancer regulating the white gene
      expression in the eyes. The ability of insulators to disrupt weak transcription
      may play a role in the enhancer-blocking activity.

PMID- 29372798
TI  - [Genetic diversity of charrs of the Commander Islands based on the analysis of
      mitochondrial DNA].
AB  - Nucleotide sequences of the mitochondrial DNA cytochrome b (CytB) gene fragment
      and the control region (D-loop) of Dolly Varden (Salvelinus malma) from the
      Commander Islands and the Kol River of the Kamchatka Peninsula were examined. A
      high level of genetic variability of island populations comparable to that of the
      mainland population of western Kamchatka was demonstrated. The belonging of the
      Commander Islands chars to the genetic lineage of northern Dolly Varden
      Salvelinus malma malma was confirmed.

PMID- 29372799
TI  - The insulin-like receptor gene expression in the tissues synthesizing
      gonadotropic hormones at sexual maturation of Drosophila melanogaster females].
AB  - The insulin/insulin-like growth factor signaling pathway is involved in the
      regulation of the synthesis of insect gonadotropic hormones, juvenile (JH) and 20
      hydroxyecdysone (20E). We carried out the immunohistochemical analysis of the
      insulin receptor (InR) expression in the corpus allatum (the JH-producing gland)
      and in the ovarian follicular cells (a site for the synthesis of 20E precursor,
      ecdysone) in the process of sexual maturation of D. melanogaster females and
      examined the influence of exogenous JH on the InR expression in these tissues.
      For the first time, it was demonstrated that InR was expressed in follicular
      cells and that its expression in corpus allatum and follicular cells of
      Drosophila females was stage-specific, i.e., the expression intensity in young
      females greatly exceeded that in mature individuals. We also found a negative
      feedback loop in the regulation of JH levels by the insulin signaling pathway in
      Drosophila adults: the experimental increase in the JH titers in young females
      dramatically reduced the InR expression intensity in corpus allatum and
      follicular cells.

PMID- 29372800
TI  - [Use of site-specific DNA endonucleases in genome-wide studies of human DNA].
AB  - During the last decades, site-specific DNA endonucleases have served as a key
      instrument to study primary structure of DNA and genetic engineering. Here, we
      describe examples of these enzyme uses in genome-wide analysis of human DNA
      including restriction endonucleases involvement during sample preparation for
      sequencing using NGS devices, as well as visualization of cleavage of DNA repeats
      by endonucleases. The first studies on application of DNA endonucleases in the
      rapidly developing area of epigenetic analysis of genomes, which is facilitated
      by the recent discovery of a new class of enzymes, 5-methylcytosinedependent site
      specific DNA endonucleases, are of special interest.

PMID- 29372801
TI  - [The evolution of heat shock genes and expression patterns of heat shock proteins
      in the species from temperature contrasting habitats].
AB  - Heat shock genes are the most evolutionarily ancient among the systems
      responsible for adaptation of organisms to a harsh environment. The encoded
      proteins (heat shock proteins, Hsps) represent the most important factors of
      adaptation to adverse environmental conditions. They serve as molecular
      chaperones, providing protein folding and preventing aggregation of damaged
      cellular proteins. Structural analysis of the heat shock genes in individuals
      from both phylogenetically close and very distant taxa made it possible to reveal
      the basic trends of the heat shock gene organization in the context of adaptation
      to extreme conditions. Using different model objects and nonmodel species from
      natural populations, it was demonstrated that modulation of the Hsps expression
      during adaptation to different environmental conditions could be achieved by
      changing the number and structural organization of heat shock genes in the
      genome, as well as the structure of their promoters. It was demonstrated that
      thermotolerant species were usually characterized by elevated levels of Hsps
      under normal temperature or by the increase in the synthesis of these proteins in
      response to heat shock. Analysis of the heat shock genes in phylogenetically
      distant organisms is of great interest because, on one hand, it contributes to
      the understanding of the molecular mechanisms of evolution of adaptogenes and, on
      the other hand, sheds the light on the role of different Hsps families in the
      development of thermotolerance and the resistance to other stress factors.

PMID- 29372802
TI  - [Detection of putative polysaccharide biosynthesis genes in Azospirillum
      brasilense strains from serogroups I and II].
AB  - It is known that in Azospirillum brasilense strains Sp245 and SR75 included in
      serogroup I, the repeat units of their O-polysaccharides consist of five residues
      of D-rhamnose, and in strain SR15, of four; and the heteropolymeric O
      polysaccharide of A. brasilense type strain Sp7 from serogroup II contains not
      less than five types of repeat units. In the present work, a complex of
      nondegenerate primers to the genes of A. brasilense Sp245 plasmids AZOBR_p6,
      AZOBR_p3, and AZOBR_p2, which encode putative enzymes for the biosynthesis of
      core oligosaccharide and O-polysaccharide of lipopolysaccharide, capsular
      polysaccharides, and exopolysaccharides, was proposed. By using the designed
      primers, products of the expected sizes were synthesized in polymerase chain
      reactions on genomic DNA of A. brasilense Sp245, SR75, SR15, and Sp7 in 36, 29,
      23, and 12 cases, respectively. As a result of sequencing of a number of
      amplicons, a high (86-99%) level of identity of the corresponding putative
      polysaccharide biosynthesis genes in three A. brasilense strains from serogroup I
      was detected. In a blotting-hybridization reaction with the biotin-labeled DNA of
      the A. brasilense gene AZOBR_p60122 coding for putative permease of the ABC
      transporter of polysaccharides, localization of the homologous gene in ~120-MDa
      plasmids of the bacteria A. brasilense SR15 and SR75 was revealed.

PMID- 29372803
TI  - [Prebreeding selection of rice with colored pericarp based on genotyping Rc and
      Pb genes].
AB  - The research was aimed at developing prebreeding resources of Kazakhstan rice
      varieties with colored pericarp for breeding. During the study, hybrid analysis
      of inheritance of the trait "colored pericarp" in breeding material used for the
      work was performed. Rice genotypes with colored pericarp, as well as white rice
      varieties possessing important breeding traits and maturing under conditions of
      the republic, were selected from the collection of the Institute of Plant Biology
      and Biotechnology, Republic of Kazakhstan. Identification of allelic status of Rc
      (red pericarp) and Pb (anthocyanin pericarp) genes was performed for selected
      samples using the PCR method. When selecting parental forms for crossing, foreign
      rice varieties with colored pericarp (Rubin, Mavr, Black rice, etc.) were used as
      recipient forms. As donors, we used local white rice varieties of Kazakhstan
      breeding adapted to the soil and climate conditions of rice growing regions
      (Madina, Marzhan, Bakanasskiy, PakLi) as well as foreign varieties. The ability
      to set hybrid caryopses and the percentage of sterility were determined in
      obtained F1 rice hybrids. As a result, the most promising prebreeding material
      was selected, which will be used for breeding Kazakhstan rice varieties with
      colored pericarp.

PMID- 29372804
TI  - [Genetic, phenotypic, and phytochemical polymorphism in Eastern European
      populations of Mentha arvensis L.]
AB  - Variability of M. arvensis from five geographically distanced populations was
      examined using morphological traits and phytochemical composition of essential
      oil and with the help of DNA fingerprinting using ISSR markers. The population
      differentiation based on morphological traits was weak. Analysis of the essential
      oil composition provided the subdivision of the sample into three groups and, on
      the basis of the composition of ISSR amplicons, into four groups of specimens. A
      high degree of genetic polymorphism of M. arvensis and substantial, though
      incomplete, population differentiation were identified. It was demonstrated that
      the population of M. arvensis from the Komi Republic was the most genetically
      isolated, while the populations from Moscow and Penza provinces were weakly
      differentiated from each other. The population from the Republic of Belarus (near
      Grodno) was genetically and phytochemically considerably different from the other
      studied populations, although morphologically indistinguishable from them. We
      argue that the differentiation was caused not only by the isolation by distance
      but also owing to the formation of three different ecotypes adapted to different
      climatic conditions.

PMID- 29372805
TI  - [Microsatellite loci variation and investigation of gene flow between two
      karyoforms of Cricetulus barabensis sensu lato (Rodentia, Cricetidae)].
AB  - We examine the diversity of six microsatellite loci and partial RAG1 exon of
      "barabensis" and "pseudogriseus" karyoforms in Cricetulus barabensis sensu lato
      species complex. A total of 435 specimens from 68 localities ranging from Altai
      to the Far East are investigated. The results of the population structure
      analysis (factor analysis and NJ tree based on Nei genetic distances) support
      subdivision into two well-differentiated clusters corresponding to the two
      karyoforms. These karyoforms are also well differentiated by the level of
      microsatellite variability. In several "barabensis" specimens, we found
      microsatellite alleles that are common in "pseudogriseus" populations but are
      otherwise absent in "barabensis." Most of these specimens originate from a single
      population in one of the zones of potential contact between karyoforms,
      Kharkhorin in Central Mongolia. These molecular results are consistent with
      previously published karyological data in suggesting that rare hybridization
      events between the two chromosomal races occur in nature.

PMID- 29372806
TI  - [Genetic variation of the mtDNA cyt b locus in topmouth gudgeon introduced into
      water bodies in the northern part of the Black Sea region].
AB  - The up-to-date phylogeographical distribution of the topmouth gudgeon
      Pseudorasbora parva Temminck et Schlegel 1846 in water bodies of the Northern
      Black Sea region is considered. Genetic variation of mtDNA cyt b gene is
      analyzed. It is established that topmouth gudgeon penetrated and spread in the
      basins of the Dnieper and Don rivers and in water bodies of Crimea from the
      secondary center of its dispersion- water bodies of Central Europe. It is
      demonstrated that haplotypes of topmouth gudgeon in the Danube delta are the most
      homologous to the haplotypes in the native range of the species in China. A
      considerable decrease in the level of genetic variation in the populations in the
      Black Sea region is reported.

PMID- 29372807
TI  - [Results of molecular genetic testing in Russian patients with Pendred syndrome
      and allelic disorders].
AB  - Pendred syndrome is an autosomal recessive inherited disorder characterized by a
      combination of sensorineural hearing impairment and euthyroid goiter; its
      clinical manifestation in children is hardly distinguishable from nonsyndromic
      hearing loss. Pendred syndrome is one of the most frequent types of syndromic
      hearing loss. Hearing impairment is accompanied by abnormal development of the
      bony labyrinth-enlarged vestibular aqueduct (EVA) and occasionally combined with
      Mondini dysplasia. Mutations in the SLC26A4 gene, which encodes the pendrin
      protein, are responsible for both Pendred syndrome and for allelic disorder
      (nonsyndromic enlarged vestibular aqueduct). The present study for the first time
      conducted molecular genetic analysis in 20 Russian patients with Pendred
      syndrome, EVA and/or Mondini dysplasia. As a result, six pathogenic mutations in
      the SLC26A4 gene were revealed in four patients. The mutation c.222G>T
      (p.Trp74Cys) was detected for the first time. Mutations were found in patients
      with Pendred syndrome and nonsyndromic EVA with or without Mondini dysplasia.
      Mutations were not detected in patients with isolated Mondini dysplasia. One
      proband with clinical diagnosis Pendred syndrome was homozygous for the c.35delG
      mutation in the GJB2 gene. The absence of frequent mutations, including well
      known ones or "hot" exons in the SLC26A4 gene, was reported. Therefore, the
      optimal method to search for mutations in the SLC26A4 gene in Russian patients is
      Sanger sequencing of all exons and exon-intron boundaries in the SLC26A4 gene.

PMID- 29372808
TI  - A Folate-Conjugated Dual-Modal Fluorescent Magnetic Resonance Imaging Contrast
      Agent that Targets Activated Macrophages In Vitro and In Vivo.
AB  - Mucin-1 (MUC1), a transmembrane glycoprotein is aberrantly expressed on ~90% of
      breast cancer and is an excellent target for nanoparticulate targeted imaging. In
      this study, the development of a dye-doped NIR emitting mesoporous silica
      nanoparticles platform conjugated to tumor-specific MUC1 antibody (ab-tMUC1-NIR
      MSN) for in vivo optical detection of breast adenocarcinoma tissue is reported.
      The structural properties, the in vitro and in vivo performance of this
      nanoparticle-based probe were evaluated. In vitro studies showed that the MSN
      based optical imaging nanoprobe is non-cytotoxic and targets efficiently mammary
      cancer cells overexpressing human tMUC1 protein. In vivo experiments with female
      C57BL/6 mice indicated that this platform accumulates mainly in the liver and did
      not induce short-term toxicity. In addition, we demonstrated that the ab-tMUC1
      NIR-MSN nanoprobe specifically detects mammary gland tumors overexpressing human
      tMUC1 in a human MUC1 transgenic mouse model.

PMID- 29372809
TI  - [Association study of genetic markers of schizophrenia and its cognitive
      endophenotypes].
AB  - A replicative analysis of associations of 15 SNPs located in the regions of 11
      genes (TCF4, VRK2, NOTCH4, ZNF804A, AGBL1, RELN, ZFP64P1, KCNB2, CSMD1, CPVL,
      NRIP1) and three intergenic regions (SLCO6A1/LINCOO491,
      LOC105376248/LOC105376249, SPA17/NRGN) with schizophrenia was conducted in the
      Russian population of the Siberian region. These SNPs were previously identified
      in genome-wide association studies (GWAS) of schizophrenia and cognitive
      abnormalities. The present study confirmed associations of KCNB2 rs2247572, CSMD1
      rs2616984, and intergenic rs12807809 located in SPA17/NRGN with schizophrenia. It
      was established that the frequency of the CSMD1 rs2616984 G/G genotype was higher
      in patients compared to the control group (OR = 1.73; CI: 1.14-2.62; r = 0.0337).
      The frequencies of the KCNB2 rs2247572 TT genotype (OR = 0.41; CI: 0.20-0.87; r =
      0.0485) and intergenic rs12807809 CT genotype located in SPA17/NRGN (OR = 0.70;
      CI: 0.53-0.94; r = 0.0464) were significantly decreased in patients compared to
      the control group.

PMID- 29372810
TI  - Treatment of coronary bifurcation lesions: current knowledge and future
      perspectives.
AB  - Coronary lesions at bifurcation sites are frequent and still remain a challenging
      subset for the interventional cardiologist. Although in the last years the
      provisional stenting technique has shown more consistent results, coronary
      bifurcation interventions still share a worse procedural success rate and
      increased rates of mid- and long-term cardiac events. Most of the dedicated
      devices proposed in the last few years have failed to show improved results when
      compared with standard devices. The broader use of imaging techniques, such as
      intravascular ultrasound and optical coherence tomography, lead to a better
      understanding of the real anatomy of bifurcations and has shown to be a great
      tool for percutaneous coronary intervention optimization. Preliminary results
      come from drug-coated balloons and bioresorbable vascular scaffolds, especially
      for the 'leave nothing behind' concept, particularly interesting in this setting
      of lesions.

PMID- 29372811
TI  - Changes in growth and sleep across school nights, weekends and a winter holiday
      period in two Australian schools.
AB  - Studies suggest that there may be an association between sleep and growth;
      however, the relationship is not well understood. Changes in biology and external
      factors such as school schedule heavily impact the sleep of adolescents, during a
      critical phase for growth. This study assessed the changes in sleep across school
      days, weekends and school holidays, while also measuring height and weight
      changes, and self-reported alterations in food intake and physical activity. The
      impact of morningness-eveningness (M-E) on height change and weight gain was also
      investigated. In a sample of 63 adolescents (mean age = 13.13, SD = 0.33, 31
      males) from two independent schools in South Australia, height and weight were
      measured weekly for 4 weeks prior to the school holidays and 4 weeks after the
      school holidays. Participants also completed a Morningness/Eveningness Scale and
      7-day sleep, diet and physical activity diaries prior to, during and after the
      school holidays. Participants at one school had earlier wake times during the
      weekends than participants attending the other school, leading to a significantly
      shorter sleep duration on weekends for those participants. Regardless of school,
      sleep was significantly later and longer during the holidays (p < 0.001) and
      those with a stronger morning preference fell asleep (F18,36 = 3.4, p = 0.001)
      and woke (F18,44 = 2.0, p = 0.027) earlier than evening types. Growth rate was
      lower during the holiday weeks. For those attending the school with limited sleep
      in opportunities, growth after the holidays was lower for those with greater
      evening preference, whereas for those at the other school, growth was greater for
      those with greater evening preference. The increase in average weight from pre-
      to post-holidays was greater for those attending the school with limited
      opportunities to sleep longer. Participants reported greater food intake during
      the holidays compared to school days and greater physical activity levels on
      weekends compared to school days, and school days compared to holidays. Results
      suggest that time of day preference may impact growth, with evening types who
      cannot sleep in growing at a slower rate than evening types who can or morning
      types. This may be related to sleep restriction. Despite sleep being both later
      and longer during the school holidays, participants' growth slowed during the
      holiday period. It is possible that this may be a reflection of other behavioural
      changes in the holidays (increased food intake and reduced physical activity), as
      sleep timing during the school period was related to growth.

PMID- 29372813
TI  - Seasonal variation of admission severity and outcomes in ischemic stroke - a
      consecutive hospital-based stroke registry.
AB  - Different morbidities and mortalities of ischemic stroke may occur among seasons.
      For detecting the seasonal variations of severity after stroke onset and
      prognosis, we employed a retrospective analysis on a prospective regional
      hospital-based stroke registry and included a total of 1039 consecutive patients
      with onset date from January 2014 to December 2015. Patients were divided into
      four groups according to the onset seasons. Baseline characteristics, stroke
      subtypes, admission National Institute of Health Stroke Scale (NIHSS) score and
      modified Rankin Scale (mRS) score in 90 d were recorded and compared. Ordinal
      logistic regression was used to evaluate the association of seasons and severity
      or outcomes. Higher proportion of cardiac embolisms appeared in spring and winter
      (p < 0.001). The median admission NIHSS score was 5 in spring, 3 in summer, 4 in
      fall and 4 in winter (p = 0.036). After 90 d from onset, 40.5% of patients in
      spring suffered poor outcome (mRS 3-6), while 24.6% in summer, 33.9% in fall and
      40.1% in winter (p < 0.001). After adjusted for age, sex, stroke subtypes and
      other covariates, patients in spring and winter had 1.76 times (95%CI 1.14-2.70,
      p = 0.010) and 1.53 times (95%CI 1.08-2.18, p = 0.017) the risk of suffering
      higher severity category than patients in summer, respectively. Compared with
      summer group, risk of worse outcomes at 90 d increased to 2.30 times in spring
      (95%CI 1.53-3.45, p < 0.001), 1.57 times in fall (95%CI 1.14-2.16, p = 0.006) and
      2.09 times in winter (95%CI 1.50-2.91, p < 0.001), respectively. In conclusion,
      onset seasons were associated with severity and outcomes in ischemic stroke, and
      patients admitted in spring and winter had more severity and worse outcomes than
      patients in summer.

PMID- 29372814
TI  - Bacillus velezensis CC09: A Potential 'Vaccine' for Controlling Wheat Diseases.
AB  - Biocontrol bacteria that can act like a "vaccine", stimulating plant resistance
      to pathogenic diseases, are still not fully elucidated. In this study, an
      endophytic bacterium, Bacillus velezensis CC09, labeled with green fluorescent
      protein, was tested for its colonization, migration, and expression of genes
      encoding iturin A synthetase within wheat tissues and organs as well as for
      protective effects against wheat take-all and spot blotch diseases. The results
      showed that strain CC09 not only formed biofilm on the root surface but was also
      widely distributed in almost every tissue, including the epidermis, cortex, and
      xylem vessels, and even migrated to stems and leaves, resulting in 66.67% disease
      control efficacy (DCE) of take-all and 21.64% DCE of spot blotch. Moreover, the
      gene cluster encoding iturin A synthase under the control of the pitu promoter is
      expressed in B. velezensis CC09 in wheat tissues, which indicates that iturin A
      might contribute to the in-vivo antifungal activity and leads to the disease
      control. All these data suggested that strain CC09 can act like a 'vaccine' in
      the control of wheat diseases, with a single treatment inoculated on roots
      through multiple mechanisms.

PMID- 29372812
TI  - Pseudomonas aeruginosa Biofilms: Host Response and Clinical Implications in Lung
      Infections.
AB  - Pseudomonas aeruginosa is a major health challenge that causes recalcitrant
      multidrug-resistant infections, especially in immunocompromised and hospitalized
      patients. P. aeruginosa is an important cause of nosocomial and ventilator
      associated pneumonia characterized by high prevalence and fatality rates. P.
      aeruginosa also causes chronic lung infections in individuals with cystic
      fibrosis. Multidrug- and totally drug-resistant strains of P. aeruginosa are
      increasing threats that contribute to high mortality in these patients. The
      pathogenesis of many P. aeruginosa infections depends on its ability to form
      biofilms, structured bacterial communities that can coat mucosal surfaces or
      invasive devices. These biofilms make conditions more favorable for bacterial
      persistence, as embedded bacteria are inherently more difficult to eradicate than
      planktonic bacteria. The molecular mechanisms that underlie P. aeruginosa biofilm
      pathogenesis and the host response to P. aeruginosa biofilms remain to be fully
      defined. However, it is known that biofilms offer protection from the host immune
      response and are also extremely recalcitrant to antimicrobial therapy. Therefore,
      development of novel therapeutic strategies specifically aimed at biofilms is
      urgently needed. Here, we review the host response, key clinical implications of
      P. aeruginosa biofilms, and novel therapeutic approaches to treat biofilms
      relevant to lung infections. Greater understanding of P. aeruginosa biofilms will
      elucidate novel avenues to improve outcomes for P. aeruginosa pulmonary
      infections.

PMID- 29372815
TI  - Understanding important issues in young-onset dementia care: the perspective of
      healthcare professionals.
AB  - AIM: Psychosocial research on the lived experiences of young-onset dementia
      patients and caregivers has identified salient issues about their care, however,
      views on care from the perspective of young-onset dementia healthcare
      professionals is less well known. The aim of this study was to investigate and
      identify important issues in young-onset dementia care provision from a
      healthcare provider perspective. METHODS: The design was an exploratory
      qualitative interview study. In-depth semistructured interviews were conducted
      with healthcare professionals with clinical expertise in young-onset dementia
      drawn from medicine, nursing and allied health. Thematic analysis was applied to
      interview transcripts to identify themes representing important underlying issues
      in care across the dementia clinical pathway (i.e., prediagnosis, diagnosis and
      postdiagnosis). RESULTS: In prediagnosis, it is important for healthcare
      professionals to recognize symptoms as organic and degenerative and more than
      psychological, and to refer patients to an appropriate clinical facility for
      assessment. During diagnosis, it may be challenging to determine dementia, and
      methods are employed to manage diagnostic uncertainty. Following diagnosis,
      optimizing routine clinical care is important and can include the provision of
      practical informational guidance, empathic concern and psychoeducational support.
      Meeting service-user requirements in the community is an important aspect of
      care, and may be facilitated by the involvement of clinical nurse specialists.
      CONCLUSION: The findings are presented as a paradigm for holistic young-onset
      dementia care. The paradigm offers a framework for contemplating and evaluating
      the criteria and quality of young-onset dementia care.

PMID- 29372816
TI  - Mechanisms of social synchrony between circadian activity rhythms in cohabiting
      marmosets.
AB  - In marmosets, social synchrony between circadian profiles of activity is stronger
      in animals that cohabit in a family. The activity of three breeding pairs was
      recorded by actiwatches to investigate the mechanisms involved in the synchrony
      between the circadian activity profiles during cohabitation in marmoset
      reproductive pairs. The dyads were submitted to LD 12:12 (21 days) and LL: 1)
      cohabitation (24 days), 2) removal of the cage mate (20 days), 3) reintroduction
      of the mate into the cage of the 1st situation (30 days) and 4) removal of the
      cage mate (7 days). Next, they were rejoined and maintained in LD 12:12 (11
      days). In conditions involving cohabitation of pair, the general and maximum
      correlation indexes between circadian profiles were higher in cage mates compared
      to animals of the same or different sex with which they maintain only acoustic
      and olfactive contact. This strong synchrony between rhythms was accompanied by a
      stable phase relationship at the activity onset and offset, with identical
      circadian periods between mates. When the pairs were separated, there was a break
      in stability in the phase relationships between activity profiles with different
      circadian periods and a greater phase angle difference between rhythms of cage
      mates. During separation, two females and one male progressively anticipated the
      activity onset and offset in a phase similar to that in previous conditions,
      expressing entrainment to the mate. During the first reintroduction, two pairs
      exhibited signs of masking in rhythm. Although modulation in the rhythm of some
      animals has been observed through acoustic cues from animals outside the colony,
      we suggest that cohabitation favors strong synchrony between the circadian
      activity profiles of marmoset reproductive pairs involving synchronization by
      entrainment and masking. Further studies in the absence of external social cues
      are necessary to clarify the role of these mechanisms on social synchronization
      in marmosets.

PMID- 29372841
TI  - Bmal1-deficient mouse fibroblast cells do not provide premature cellular
      senescence in vitro.
AB  - Bmal1 is a core circadian clock gene. Bmal1-/- mice show disruption of the clock
      and premature aging phenotypes with a short lifespan. However, little is known
      whether disruption of Bmal1 leads to premature aging at cellular level. Here, we
      established primary mouse embryonic fibroblast (MEF) cells derived from Bmal1-/-
      mice and investigated its effects on cellular senescence. Unexpectedly, Bmal1-/-
      primary MEFs that showed disrupted circadian oscillation underwent neither
      premature replicative nor stress-induced cellular senescence. Our results
      therefore uncover that Bmal1 is not required for in vitro cellular senescence,
      suggesting that circadian clock does not control in vitro cellular senescence.

PMID- 29372842
TI  - Decreased daytime light intensity at nonwindow hospital beds: Comparisons with
      light intensity at window hospital beds and light exposure in nonhospitalized
      elderly individuals.
AB  - Light is crucial for the synchronization of internal biological rhythms with
      environmental rhythms. Hospitalization causes a range of unfavorable medical
      conditions, including delirium, sleep disturbances, depressed mood, and increased
      fall, especially in elderly people. The hospital room environment contributes
      significantly to patients' circadian physiology and behavior; however, few
      studies have evaluated light intensity in hospital settings. In this study,
      bedside light intensity during the daytime (6:00-21:00) was measured at 1-min
      intervals using a light meter on 4869 bed-days at the Inabe General Hospital in
      Mie, Japan (latitude 35 degrees N), for approximately 1 month in each season.
      Daytime light exposure in home settings was measured in nonhospitalized elderly
      individuals (n = 1113) for two consecutive days at 1-min intervals using a wrist
      light meter. Median daytime light intensities at window and nonwindow hospital
      beds were 327.9 lux [interquartile range (IQR), 261.5-378.4] and 118.4 lux (IQR,
      100.6-142.9), respectively, and daytime light intensity measured in
      nonhospitalized elderly individuals was 337.3 lux (IQR, 165.5-722.7). Compared
      with data in nonhospitalized elderly individuals, nonwindow beds were exposed to
      significantly lower daytime light intensity (p < 0.001), whereas window beds were
      exposed to similar daytime light intensity to that of home settings (p = 1.00).
      These results were consistent regardless of seasons (spring, summer, fall, and
      winter) or room directions (north vs. south facing). The lowest median daytime
      light intensity was observed at nonwindow beds in north-facing rooms during the
      winter (84.8 lux; IQR, 76.0-95.8). Further studies evaluating the incidence of in
      hospital outcomes between patients hospitalized in window and nonwindow beds are
      needed.

PMID- 29372843
TI  - Analysis of Fusion Genes by NanoString System: A Role in Lung Cytology?
AB  - CONTEXT: - Patients with non-small cell lung cancer harboring ALK receptor
      tyrosine kinase ( ALK), ROS proto-oncogene 1 ( ROS1), and ret proto-oncogene (
      RET) gene rearrangements can benefit from specific kinase inhibitors. Detection
      of fusion genes is critical for determining the best treatment. Assessing
      rearrangements in non-small cell lung cancer remains challenging, particularly
      for lung cytology. OBJECTIVE: - To examine the possible application of the
      multiplex, transcript-based NanoString system (NanoString Technologies, Seattle,
      Washington) in the evaluation of fusion genes in lung adenocarcinoma samples.
      DATA SOURCES: - This study is a narrative literature review. Studies about
      NanoString, gene fusions, and lung adenocarcinoma were collected from PubMed
      (National Center for Biotechnology Information, Bethesda, Maryland). We found 7
      articles about the application of the NanoString system to detect fusion genes on
      formalin-fixed, paraffin-embedded tumor tissues and one article evaluating the
      adequacy of lung cytologic specimens for NanoString gene expression analysis.
      CONCLUSIONS: - To maximize the yield of molecular tests on small lung biopsies,
      the NanoString nCounter system has been suggested to detect fusion genes.
      NanoString fusion gene assays have been successfully applied on formalin-fixed,
      paraffin-embedded tissues. Although there are only a few studies available, the
      application of NanoString assays may also be feasible in lung cytology. According
      to available data, the NanoString system could strengthen the routine molecular
      characterization of lung adenocarcinoma.

PMID- 29372844
TI  - Molecular Testing of Non-Small Cell Lung Carcinoma Diagnosed by Endobronchial
      Ultrasound-Guided Transbronchial Fine-Needle Aspiration.
AB  - CONTEXT: - Given the increasing demand for molecular testing of non-small cell
      lung carcinoma specimens to guide therapeutic decision-making, and the trend
      toward minimally invasive techniques for obtaining diagnostic tissue,
      cytopathology laboratories must devise strategies to maximize DNA yield for
      necessary molecular testing. OBJECTIVE: - To describe our experience at Cleveland
      Clinic with epidermal growth factor receptor ( EGFR) mutation testing by next
      generation sequencing and anaplastic lymphoma kinase ( ALK) gene rearrangement
      testing by fluorescence in situ hybridization of non-small cell lung carcinomas
      diagnosed by cytology, with an emphasis on specimens obtained by endobronchial
      ultrasound-guided transbronchial fine-needle aspiration. DATA SOURCES: - Data
      sources include a review of the current literature, including published articles
      from our institution. CONCLUSIONS: - At our institution, liquid-based cytology
      specimens are the primary resource used for molecular testing of non-small cell
      lung carcinomas; in most instances, adequate DNA can be extracted from the
      residual cell pellet for next-generation sequencing, and ThinPrep slides can be
      used reliably for fluorescence in situ hybridization testing for ALK gene
      rearrangements. In occasional cases where the cell pellet material is not
      adequate for molecular testing, cell blocks and/or surgical pathology specimens
      are secondary options. The cytopathologist's role in specimen handling and triage
      is essential to ensure that molecular testing can be carried out successfully.

PMID- 29372845
TI  - Myeloid Neoplasm With Germline Predisposition: A 2016 Update for Pathologists.
AB  - CONTEXT: - Myeloid neoplasms with familial occurrence have been rarely reported
      in the past. With the advance of molecular technology and better understanding of
      the molecular pathogenesis of myeloid neoplasms, investigating the genetic causes
      of familial acute myeloid leukemia or myelodysplastic syndrome has become
      feasible in the clinical setting. Recent studies have identified a rapidly
      expanding list of germline mutations associated with increased risks of
      developing myeloid neoplasm in the affected families. It is important to
      recognize these entities, as such a diagnosis may dictate a unique approach in
      clinical management and surveillance for the patients and carriers. OBJECTIVE: -
      To raise the awareness of myeloid neoplasms arising in the setting of familial
      inheritance among practicing pathologists. DATA SOURCES: - Based on recent
      literature and the 2016 revision of the World Health Organization classification
      of hematopoietic neoplasms, we provided an up-to-date review of myeloid neoplasm
      with germline predisposition. CONCLUSIONS: - This short review focused on the
      clinical, pathologic, and molecular characterization of myeloid neoplasm with
      germline predisposition. We emphasized the important features that will help
      practicing pathologists to recognize these newly described entities.

PMID- 29372847
TI  - In Reply.

PMID- 29372846
TI  - Pathology of Melanotic Schwannoma.
AB  - CONTEXT.-: Melanotic schwannoma (MS) is a nerve sheath tumor with a uniform
      composition of variably melanin-producing Schwann cells and metastatic potential.
      The MS is an uncommon neoplasm, accounting for less than 1% of all nerve sheath
      tumors, with a predilection for spinal nerve involvement. Microscopically, the
      tumors are characterized by spindle and epithelioid cells arranged in interlacing
      fascicles, with marked accumulation of melanin in neoplastic cells and associated
      melanophages. The MSs are frequently associated with Carney complex, showing
      features of psammoma bodies and adipose-like cells. Strict criteria of malignancy
      in MS are not well developed, although a combination of worrisome histologic
      features (large, vesicular nuclei, with macronucleoli, brisk mitotic activity,
      and necrosis) raises concern for aggressive behavior. OBJECTIVE.-: To review the
      current status of the MS literature, discussing putative etiology,
      histopathology, current genetics, and differential diagnoses, including overlap
      with other pigmented tumors. DATA SOURCES.-: Search of PubMed (National Center
      for Biotechnology Information, Bethesda, Maryland) and the authors' own
      experiences. CONCLUSIONS.-: The occurrence of MS at several unusual anatomic
      sites and its spectrum of morphologic patterns can result in significant
      diagnostic difficulty, and correct diagnosis is particularly important because of
      its high tendency to recur locally and to metastasize, which highlights the
      importance of diagnostic recognition, ancillary molecular genetic testing, and
      close clinical follow-up of patients with MS.

PMID- 29372848
TI  - Hepatic Epithelioid Hemangioendothelioma.
AB  - Epithelioid hemangioendothelioma is a rare vascular tumor, composed of
      epithelioid and histiocytoid vascular endothelial cells in myxoid or fibrotic
      stroma, which can arise in multiple locations throughout the body. In the liver,
      this neoplasm usually presents on imaging as an incidental finding of multifocal,
      heterogeneously enhancing nodules in both lobes or presents clinically with
      nonspecific abdominal symptoms. Histologically, the tumor has been mistaken for
      metastatic carcinoma, angiosarcoma, hepatocellular carcinoma, and
      cholangiocarcinoma. The neoplasm usually stains positive for vascular markers,
      such as factor VIII-related antigen, CD31, and CD34, and negative for
      cytokeratins. The translocation t(1;3)(p36.3;q25), resulting in the CAMTA1- WWTR1
      fusion product, is the most commonly identified genetic abnormality with this
      tumor. Although hepatic epithelioid hemangioendothelioma can have a varied
      clinical course, it is generally considered less aggressive than angiosarcoma.
      There is no consensus treatment protocol and techniques including liver
      transplantation, liver resection, chemotherapy and/or radiation therapy, and
      surveillance have all been used with varying outcomes.

PMID- 29372849
TI  - Historical Insights for Early Adopters of Whole Slide Imaging.

PMID- 29372850
TI  - In Defense of the Academic Autopsy.

PMID- 29372851
TI  - A New Kind of Autopsy for 21st Century Medicine.

PMID- 29372852
TI  - Primary Breast Atypical Lipomatous Tumor/ Well-Differentiated Liposarcoma and
      Dedifferentiated Liposarcoma.
AB  - Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and its
      higher-grade counterpart, dedifferentiated liposarcoma (DDL), are extraordinarily
      rare tumors in the breast. The main differential diagnostic consideration of
      primary breast ALT/WDL is malignant phyllodes tumor with liposarcomatous
      differentiation, and the main differential diagnostic consideration of DDL in the
      breast is metaplastic breast carcinoma, particularly the spindle cell type, with
      heterologous sarcomatous differentiation. These differential diagnoses may be
      particularly challenging when evaluating limited core needle biopsy sampling.
      MDM2 and/or CDK4 protein overexpression and gene amplification are beneficial
      ancillary studies that can help establish the diagnosis of primary breast ALT/WDL
      and DDL, and effectively rule out the diagnoses of malignant phyllodes tumor and
      metaplastic breast carcinoma.

PMID- 29372853
TI  - A standardized protocol to reduce pediatric baclofen pump infections: a quality
      improvement initiative.
AB  - OBJECTIVE Intrathecal baclofen pumps are generally placed in children for the
      treatment of spasticity and dystonia. Use of implants in this pediatric
      population with comorbidities is reported to have a high risk of complications
      and infections. With the aim of reducing baclofen pump-related infections, a
      quality improvement project was instituted at the authors' institution. METHODS A
      workflow paradigm unique to baclofen pump implantation aimed at decreasing
      implant-related infections was implemented. All baclofen pump operations
      performed at the authors' institution between August 2012 and June 2016 were
      reviewed. An infection prevention protocol was created and implemented in August
      2014 based on a literature review and the consensus opinion of the pediatric
      neurosurgeons in the group. Compliance with the prevention bundle was tracked.
      Case outcomes before and after implementation of the protocol with a minimum of 3
      months of follow-up were retrospectively reviewed. Univariate and multivariate
      analyses were performed to assess the association of the steps in the prevention
      bundle with infection and complication outcomes. RESULTS A total of 128 baclofen
      pump surgeries were performed (64 preprotocol and 64 postprotocol). The patient
      age range was 3 to 27 years. The overall compliance rate with the infection
      prevention bundle was 82%. The pre- and postimplementation infection rates were
      12.5% and 6.3%, respectively (p = 0.225). The total pre- and postimplementation
      complication rates were 23.4% and 9.4%, respectively (p = 0.032). The absolute
      and relative risk reductions for infections were 6.3% (95% CI 3.8%-16.3%) and
      50%, respectively; for complications, the absolute and relative risk reductions
      were 14.1% (95% CI 1.5%-26.7%) and 60%, respectively. CONCLUSIONS The total
      complication rate following intrathecal baclofen pump surgery was significantly
      lower after implementation of the quality improvement protocol. This study is an
      example of using checklist standardization to diminish special cause variability.

PMID- 29372854
TI  - Adenosine-induced cardiac standstill for endovascular treatment of pediatric vein
      of Galen malformations.
AB  - Vein of Galen malformations are congenital high-flow vascular malformations that
      often present with heart failure, hydrocephalus, developmental delay, and
      intracranial hemorrhage. Because open surgical treatment is associated with high
      morbidity and mortality, endovascular embolization is increasingly becoming the
      preferred method of intervention. However, embolization of these lesions can be
      difficult because of their high-flow nature. The use of adenosine-induced cardiac
      standstill for treatment of vein of Galen malformations has not been previously
      described in neonates. The authors describe 3 treatments in 2 patients that
      demonstrate that the use of adenosine is well tolerated and allows safe
      transarterial embolization of high-flow vein of Galen malformations in the
      pediatric population.

PMID- 29372855
TI  - Placement of baclofen pump catheter through a C1-2 puncture: technical note.
AB  - Intrathecal baclofen has been suggested as an effective and safe treatment for
      intractable spasticity and dystonia. Techniques of lumbar and intraventricular
      catheter placement have been previously described. The purpose of this study was
      to describe a technique to implant catheters for intrathecal baclofen infusion
      through C1-2 puncture. Four of 5 consecutively treated patients underwent
      successful placement of catheters for intrathecal baclofen. There were no
      instances of infection, CSF leak, or catheter migration seen during a follow-up
      period of at least 6 months; furthermore, there were no occurrences of vertebral
      artery or spinal cord injury. All patients had an effective stabilization or
      reduction of their upper-extremity, lower-extremity, or trunk tone. There were no
      cases of worsening hypertonia. The authors' preliminary experience with C1-2
      puncture for placement of the intrathecal baclofen catheter seems to indicate
      that this is a safe and efficacious technique. Lessons learned from the failed
      attempt at C1-2 puncture will be delineated.

PMID- 29372856
TI  - Editorial. Damage capitation as malpractice reform.

PMID- 29372857
TI  - Early experience of placing image-guided minimally invasive pedicle screws
      without K-wires or bone-anchored trackers.
AB  - OBJECTIVE Image guidance for spine surgery has been reported to improve the
      accuracy of pedicle screw placement and reduce revision rates and radiation
      exposure. Current navigation and robot-assisted techniques for percutaneous
      screws rely on bone-anchored trackers and Kirchner wires (K-wires). There is a
      paucity of published data regarding the placement of image-guided percutaneous
      screws without K-wires. A new skin-adhesive stereotactic patient tracker
      (SpineMask) eliminates both an invasive bone-anchored tracker and K-wires for
      pedicle screw placement. This study reports the authors' early experience with
      the use of SpineMask for "K-wireless" placement of minimally invasive pedicle
      screws and makes recommendations for its potential applications in lumbar fusion.
      METHODS Forty-five consecutive patients (involving 204 screws inserted) underwent
      K-wireless lumbar pedicle screw fixation with SpineMask and intraoperative
      neuromonitoring. Screws were inserted by percutaneous stab or Wiltse incisions.
      If required, decompression with or without interbody fusion was performed using
      mini-open midline incisions. Multimodality intraoperative neuromonitoring
      assessing motor and sensory responses with triggered electromyography (tEMG) was
      performed. Computed tomography scans were obtained 2 days postoperatively to
      assess screw placement and any cortical breaches. A breach was defined as any
      violation of a pedicle screw involving the cortical bone of the pedicle. RESULTS
      Fourteen screws (7%) required intraoperative revision. Screws were removed and
      repositioned due to a tEMG response < 13 mA, tactile feedback, and 3D
      fluoroscopic assessment. All screws were revised using the SpineMask with the
      same screw placement technique. The highest proportion of revisions occurred with
      Wiltse incisions (4/12, 33%) as this caused the greatest degree of SpineMask
      deformation, followed by a mini midline incision (3/26, 12%). Percutaneous screws
      via a single stab incision resulted in the fewest revisions (7/166, 4%).
      Postoperative CT demonstrated 7 pedicle screw breaches (3%; 5 lateral, 1 medial,
      1 superior), all with percutaneous stab incisions (7/166, 4%). The radiological
      accuracy of the SpineMask tracker was 97% (197/204 screws). No patients suffered
      neural injury or required postoperative screw revision. CONCLUSIONS The
      noninvasive cutaneous SpineMask tracker with 3D image guidance and tEMG
      monitoring provided high accuracy (97%) for percutaneous pedicle screw placement
      via stab incisions without K-wires.

PMID- 29372859
TI  - Editorial. Developing next-generation systems for surgical navigation.

PMID- 29372858
TI  - Myositis following spine radiosurgery for metastatic disease: a case series.
AB  - OBJECTIVE Spinal stereotactic body radiation therapy (SBRT) has emerged as an
      attractive method to deliver high doses of radiation to oligometastatic spinal
      tumors with radioresistant histology. Because SBRT is a palliative therapy,
      attention to potential radiation toxicities is paramount when counseling
      patients. The objective of this study was to report radiation-induced myositis
      after SBRT, a previously undescribed complication. METHODS A total of 667
      patients received 891 spine SBRT treatments (either 24 Gy in 1 fraction or 27 Gy
      in 3 fractions) from 2011 to 2016 and underwent retrospective review. Eleven
      patients were identified as having radiographic evidence of myositis following
      SBRT. Clinical and pathologic results were collected, including receipt of anti
      vascular endothelial growth factor (VEGF) therapy, radiation dose, equivalent
      dose in 2-Gy fractions (EQD2), biologically effective dose (BED), and volume of
      muscle treated. Treatment toxicities were classified according to the Common
      Terminology Criteria for Adverse Events (CTCAE; version 4.03). Univariate
      statistical analyses were performed to evaluate the relationships between
      radiation fractionation schedule and myositis and between anti-VEGF therapy and
      myositis. RESULTS The cumulative incidence of myositis was 1.9% at 1 year. The
      median of the mean dose administered to muscle with myositis was 17.5 Gy. The
      median EQD2 was 55.1 Gy, and the median BED was 82.7 Gy. The median time to the
      development of clinical symptoms was 1.4 months, while the median time to imaging
      evidence was 4.7 months. Two patients (18.2%) had CTCAE grade 3 complications.
      Single-fraction spine SBRT (HR 4.5, 95% CI 1.2-16.9; p = 0.027) was associated
      with increased risk of developing myositis whereas receipt of anti-VEGF therapy
      was not (HR 2.2, 95% CI 0.6-7.1; p = 0.2). CONCLUSIONS Radiation myositis
      following spinal radiosurgery is a rare but important complication. Single
      fraction treatment schedules may be associated with increased risk of myositis
      but should be validated in a larger series.

PMID- 29372860
TI  - Prospective, randomized, multicenter study with 2-year follow-up to compare the
      performance of decompression with and without interlaminar stabilization.
AB  - OBJECTIVE Surgical decompression is extremely effective in relieving pain and
      symptoms due to lumbar spinal stenosis (LSS). Decompression with interlaminar
      stabilization (D+ILS) is as effective as decompression with posterolateral fusion
      for stenosis, as shown in a major US FDA pivotal trial. This study reports a
      multicenter, randomized controlled trial in which D+ILS was compared with
      decompression alone (DA) for treatment of moderate to severe LSS. METHODS Under
      approved institutional ethics review, 230 patients (1:1 ratio) randomized to
      either DA or D+ILS (coflex, Paradigm Spine) were treated at 7 sites in Germany.
      Patients had moderate to severe LSS at 1 or 2 adjacent segments from L-3 to L-5.
      Outcomes were evaluated up to 2 years postoperatively, including Oswestry
      Disability Index (ODI) scores, the presence of secondary surgery or lumbar
      injections, neurological status, and the presence of device- or procedure-related
      severe adverse events. The composite clinical success (CCS) was defined as
      combining all 4 of these outcomes, a success definition validated in a US FDA
      pivotal trial. Additional secondary end points included visual analog scale (VAS)
      scores, Zurich Claudication Questionnaire (ZCQ) scores, narcotic usage, walking
      tolerance, and radiographs. RESULTS The overall follow-up rate was 91% at 2
      years. There were no significant differences in patient-reported outcomes at 24
      months (p > 0.05). The CCS was superior for the D+ILS arm (p = 0.017). The risk
      of secondary intervention was 1.75 times higher among patients in the DA group
      than among those in the D+ILS group (p = 0.055). The DA arm had 228% more lumbar
      injections (4.5% for D+ILS vs 14.8% for DA; p = 0.0065) than the D+ILS one.
      Patients who underwent DA had a numerically higher rate of narcotic use at every
      time point postsurgically (16.7% for D+ILS vs 23% for DA at 24 months). Walking
      Distance Test results were statistically significantly different from baseline;
      the D+ILS group had > 2 times the improvement of the DA. The patients who
      underwent D+ILS had > 5 times the improvement from baseline compared with only 2
      times the improvement from baseline for the DA group. Foraminal height and disc
      height were largely maintained in patients who underwent D+ILS, whereas patients
      treated with DA showed a significant decrease at 24 months postoperatively (p <
      0.001). CONCLUSIONS This study showed no significant difference in the individual
      patient-reported outcomes (e.g., ODI, VAS, ZCQ) between the treatments when
      viewed in isolation. The CCS (survivorship, ODI success, absence of neurological
      deterioration or device- or procedure-related severe adverse events) is
      statistically superior for ILS. Microsurgical D+ILS increases walking distance,
      decreases compensatory pain management, and maintains radiographic foraminal
      height, extending the durability and sustainability of a decompression procedure.
      Clinical trial registration no.: NCT01316211 (clinicaltrials.gov).

PMID- 29372861
TI  - Safety and efficacy of balloon kyphoplasty at 4 or more levels in a single
      anesthetic session.
AB  - OBJECTIVE In this case series, the authors evaluated the safety of balloon
      kyphoplasty at 4 or more vertebral levels in a single anesthetic session. The
      current standard is that no more than 3 levels should be cemented at one time
      because of a perceived risk of increased complications. METHODS A retrospective
      chart review was performed for 19 consecutive patients who underwent >= 4-level
      balloon kyphoplasty between July 1, 2011, and December 31, 2015. Outcomes
      documented included kyphoplasty-associated complications and incidences of
      subsequent vertebral fracture. RESULTS Nineteen patients aged 22 to 95 years
      (mean 66.1 years, median 66 years; 53% male, 47% female) had 4 or more vertebrae
      cemented during the same procedure (mean 4.6 levels [62 thoracic, 29 lumbar]). No
      postoperative anesthetic complication, infection, extensive blood loss,
      symptomatic cement leakage, pneumothorax, or new-onset anemia was observed. Five
      patients experienced new compression fracture within a mean of 278 days
      postoperatively. One patient with metastatic cancer suffered bilateral pulmonary
      embolism 19 days after surgery, but no evidence of cement in the pulmonary
      vasculature was found. CONCLUSIONS In this case series, kyphoplasty performed on
      4 or more vertebral levels was not found to increase risk to patient safety, and
      it might decrease unnecessary risks associated with multiple operations. Also,
      morbidity associated with leaving some fractures untreated because of an
      unfounded fear of increased risk of complications might be decreased by treating
      4 or more levels in the same anesthetic session.

PMID- 29372862
TI  - Damage capitation in the modern liability climate: a primer for neurosurgeons and
      systematic review of the literature.
AB  - OBJECTIVE Neurosurgery, and particularly spine surgery, is among the most highly
      litigated medical specialties in the US, rendering the current malpractice
      climate of primary importance to spine surgeons nationwide. One of the primary
      methods of tort reform in the civil justice system is malpractice damage
      capitation (or "caps"); however, its efficacy is widely debated. The purpose of
      this article is to serve as a review for the practicing neurosurgeon, with
      particular emphasis on short- and long-term effects of damage caps and on the
      current debate regarding their utility, based on a systematic review of the
      literature. METHODS The Meta-Analysis of Observational Studies in Epidemiology
      (MOOSE) guidelines for systematic review of observational studies were used in
      the design of the study. Multiple medical and legal online databases (MEDLINE,
      Scopus, EMBASE, and JSTOR) were queried using the key words "malpractice" and
      "damage capitation" for articles from 2000 to 2014. A total of 96 abstracts were
      screened for inclusion and exclusion criteria. Of these, 22 articles were
      reviewed in full and another 15 were excluded for study design or poor quality of
      data. Five more studies were added after cross-checking the bibliographies of the
      included articles. The resulting 12 articles were evaluated; relevant data were
      extracted using a standardized metric. RESULTS Five studies were found showing
      varying effects of capitation on physician availability, with only 1 of these
      specifically showing increased availability of neurosurgery and elective spine
      coverage in states with capitation. Four studies demonstrated that capitation
      overall succeeds in decreasing jury awards and frequency of claims filed. Last, 3
      studies were found showing an overall decrease in malpractice premiums for states
      that passed damage capitation. CONCLUSIONS There is evidence in the literature
      showing that total and noneconomic damage capitation has the potential to improve
      the practice environment for neurosurgeons nationwide. Additionally, there are
      other factors that affect malpractice premium rates, such as the investment
      markets, which are not affected by these laws. All of these are important for
      spine surgeons to consider and be aware of in advocating for appropriate reform
      measures in their states.

PMID- 29372863
TI  - Ossified ligamentum flavum of the thoracic spine presenting as spontaneous
      intracranial hypotension: case report.
AB  - Ossification of the ligament flavum in the thoracic spine is an uncommon
      radiological finding in the Western population but can present with back pain,
      varying degrees of myelopathy, and even paraplegia on occasion. The authors here
      present the case of a 50-year-old woman with a history of progressive back pain
      and symptoms of spontaneous intracranial hypotension who was found to have an
      ossified ligamentum flavum of the thoracic spine resulting in a dural erosion
      cerebrospinal fluid leak. Surgery involved removal of the ossified ligament
      flavum at T10-11, facetectomy, ligation of the nerve root, and primary closure of
      the dura, which resulted in complete resolution of the patient's symptoms.
      Radiological, clinical, and intraoperative findings are discussed to assist
      surgeons with an accurate diagnosis and treatment in the setting of this unusual
      presentation.

PMID- 29372864
TI  - Beauty parlor stroke syndrome due to a bone fragment from an osteophyte of the
      atlas: case report.
AB  - Beauty parlor stroke syndrome (BPSS) is a rare condition characterized by
      mechanical impingement of a vertebral artery (VA) during neck rotation and/or
      hyperextension followed by vertebrobasilar insufficiency. However, there have
      been no reports of BPSS in which the cause of mechanical impingement was
      identified and no cases for which surgical treatment was reported. The authors
      report the case of a 56-year-old Japanese man who presented with presyncope that
      occurred during cervical extension. Given the possibility of vertebrobasilar
      insufficiency, digital subtraction angiography and CT angiography were performed.
      These studies revealed that the right VA was hypoplastic and the left VA was
      dominant. Moreover, in the position of cervical extension, the dominant left VA
      showed constriction caused by a bone fragment of an osteophyte of the atlas.
      Removal of the bone fragment was performed. Postoperative left vertebral
      angiography showed improvement of blood flow in the extended position, and the
      presyncope completely disappeared. The pathomechanism of this case was a bone
      fragment compressing the left VA in the C-1 groove during neck extension. In BPSS
      patients with recurrent transient symptoms, the possibility of this mechanism of
      VA constriction by a free bone fragment should be considered.

PMID- 29372865
TI  - Encrusted Cystitis with Suspected Ureteral Obstruction Following Cystoscopic
      Guided Laser Ablation of Ectopic Ureters in a Dog.
AB  - A 1 yr old 30 kg spayed female Labrador retriever presented for stranguria and
      hematuria 3 wk after cystoscopic laser ablation for ectopic ureters. Encrusted
      cystitis was diagnosed based on ultrasonography, cystoscopy, urinalysis, and
      culture of Corynebacterium urealyticum from the urine. Unilateral hydronephrosis
      and hydroureter were suspected to be secondary to obstruction at the trigone. The
      dog was treated with focal debridement of plaques at the left ureter, urinary
      acidification, and long-term antibiotic therapy with complete recovery. This is
      the first report of encrusted cystitis as a complication of cystoscopic-guided
      laser ablation for ectopic ureters, and suggests cystoscopic debridement may be
      useful if ureteral obstruction occurs.

PMID- 29372866
TI  - A Comparison of Ex Vivo Leak Pressures for Four Enterotomy Closures in a Canine
      Model.
AB  - Initial and maximum intraluminal leak pressures of four enterotomy closures were
      compared. Closure patterns included a modified Gambee, simple interrupted, simple
      continuous, and skin staple closure. Forty-eight 3-cm enterotomy constructs were
      created from jejunal segments harvested from 12 dogs. Twelve each were randomly
      assigned to the four closure methods. Time of closure, as well as initial and
      maximum leak pressures, were measured and compared. The modified Gambee closure
      was the slowest closure to perform, with skin staple closure being the fastest.
      All suture patterns tested had higher mean initial leak pressures than reported
      physiologic intestinal pressures during peristalsis, although the skin staple
      closures resulted in leakage below normal physiologic pressure in several
      samples. The modified Gambee closure was able to sustain a significantly higher
      initial leak pressure than skin staple closures. The modified Gambee suture
      pattern had the greatest maximum leak pressure of all enterotomy closure patterns
      tested. Use of the modified Gambee suture pattern should be considered in
      enterotomy closure, although in vivo studies are required to determine if these
      differences are clinically significant.

PMID- 29372867
TI  - Treatment of Sinonasal Aspergillosis by Debridement and Sinonasal Deposition
      Therapy with Clotrimazole Under Rhinoscopic Guidance.
AB  - Rhinoscopy was performed on 10 dogs with sinonasal aspergillosis (SNA). Direct
      access to the sinus via the nasal ostium was possible with a flexible endoscope
      to allow sinuscopy. Debridement of fungal plaques in the frontal sinus and the
      nasal cavity was performed, and a sinus and nasal deposition therapy with
      clotrimazole (1%) cream was made under rhinoscopic guidance. No oral medication
      was administered following the procedure. A rhinoscopic follow-up was performed
      monthly until cure. Six of ten (60%) dogs presented fungal plaques in the nasal
      cavity and in the frontal sinus and 4/10 (40%) dogs presented fungal plaques only
      in the frontal sinus. Five of ten (50%) dogs were considered to be cured at the
      first follow-up rhinoscopy, 4/10 (40%) after the second follow-up, and 1/10 (10%)
      after the third. Two dogs had delayed recurrence of SNA rhinoscopically assessed
      12 and 21 mo, respectively, after the last clotrimazole treatment. Endoscopic
      debridement of fungal plaques and clotrimazole (1%) cream deposition therapy
      seems to be a valuable minimally invasive technique for SNA treatment in dogs
      without the use of complementary oral medication. Delayed recurrence is a
      potential finding following treatment of SNA.

PMID- 29372868
TI  - Short-Term Prospective Clinical Evaluation of a Polyglycolic Acid Tibial
      Tuberosity Advancement Cage Implant.
AB  - This study investigated the short-term radiographic healing of the osteotomy
      following tibial tuberosity advancement (TTA), maintenance of patellar tendon
      angle (PTA), and complications in dogs receiving a polyglycolic acid (PGA) TTA
      cage. Patients diagnosed with unilateral cranial cruciate ligament disease
      requiring a 9- or 12-mm TTA cage were included. Twenty-six consecutive client
      owned dogs were prospectively selected for this clinical study. Age, weight, sex,
      breed, cage size, surgery date, and follow-up time were recorded. Radiographs
      were scored for healing and measured for PTA immediately, at 6 wk, and at 10 wk
      postoperatively. All stifles were assessed for complications throughout the study
      period. Stifles with PGA cages had similar overall healing scores compared to
      previously reported values for metallic cages, and the PTA was well maintained at
      6 and 10 wk postoperatively. Polyglycolic acid cages were associated with a
      higher complication rate (10/26, 38%; 95% confidence interval, 0.19-0.61)
      compared with previously reported complication rates for metallic cages. Despite
      favorable healing scores and overall PTA maintenance, PGA cage use resulted in a
      high complication rate. Proposed advantages offered by this particular implant
      over currently used metallic cages are offset by this high complication rate.
      Additional investigation of bioabsorbable materials and implant design should be
      considered.

PMID- 29372869
TI  - VMAT Stereotactic Body Radiation Therapy in a Multimodal Approach to a Carotid
      Paraganglioma in a Dog.
AB  - A 7 yr old female pit bull terrier was presented for a cervical soft tissue
      swelling located in the left jugular region. No abnormalities were present at
      physical examination or in the laboratory workup. Computed tomography and MRI
      scans showed a well-defined, ovoid, single mass in the left dorsal cervical
      region connected to the common carotid artery, histologically consistent with
      carotid body paraganglioma. The mass was surgically resected. Frameless
      stereotactic body radiation therapy with volumetric modulated arc therapy was set
      up as adjuvant treatment. After radiation therapy, systemic chemotherapy with
      carboplatin was started. During the first yr of follow-up, acute grade I
      dermatitis and grade I left-side laryngeal mucositis were recognized. One yr
      after radiation therapy, no signs of late radiotoxicity or tumor recurrence were
      observed. Grade I thrombocytopenia concurrent with chemotherapy was observed.
      This is the first reported case of a carotid body paraganglioma treated by
      multimodal therapy, with surgical resection and adjuvant radiotherapy and
      chemotherapy. Stereotactic body radiation therapy with volumetric modulated arc
      therapy treatment after surgery provided excellent disease control and was well
      tolerated with slight side effects.

PMID- 29372870
TI  - Stereotactic Volume Modulated Arc Radiotherapy in Canine Meningiomas: Imaging
      Based and Clinical Neurological Posttreatment Evaluation.
AB  - A prospective study to assess high-dose hypofractionated volume modulated arc
      radiotherapy feasibility and efficacy in canine meningiomas was conducted. Thirty
      nine patients with encephalic and spinal meningiomas assumed from MRI findings
      were recruited and received high-dose hypofractionated volumetric modulated arc
      radiotherapy by a linear accelerator equipped with an external beam modulator
      micro-multileaf collimator and an XVI cone beam computed tomography system. The
      prescribed mean dose was 33 Gy in five fractions. The treatment feasibility was
      tested through planned and delivered dose agreement checks. Regular clinical
      examinations were performed during and after irradiation time, with regard to
      mentation, deambulation, cranial nerve dysfunction, and seizures. Serial MRI
      exams were done 60 days after irradiation and after 4, 6, 12, 18, and 24 mo.
      Volumetric disease reduction criteria implemented with clinical neurological
      systematic evaluation were adopted to assess the course and to categorize
      patients' responses. Complete and partial responses were observed on the whole in
      65.5% of alive patients 24 mo after irradiation. Two-yr overall and disease
      specific survival rates were 74.3% and 97.4%, respectively, and the putative
      radiotoxic effects were found to be few and slight.

PMID- 29372871
TI  - Clinical Features of English Bulldogs with Presumed Arrhythmogenic Right
      Ventricular Cardiomyopathy: 31 Cases (2001-2013).
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of
      sudden death in people and boxer dogs that has recently been described in English
      bulldogs. The objective of this retrospective study was to describe the clinical
      characteristics of English bulldogs with presumed ARVC. The medical records were
      searched for English bulldogs examined between 2001 and 2013 with a clinical
      diagnosis of ARVC. The average age of the 31 dogs identified was 9.2 +/- 1.6 yr
      (range 7-13 yr). Males were overrepresented by a factor of 2.9 to 1. At initial
      presentation, 5 dogs had subclinical arrhythmia, 10 dogs had clinical signs
      attributable to arrhythmia, and 16 dogs had congestive heart failure. Eighteen
      dogs (58%) had ventricular tachycardia and five (16%) also had supraventricular
      arrhythmias. Four dogs experienced sudden death, 2 dogs died from congestive
      heart failure, 11 dogs were euthanized for cardiac causes, and 2 dogs died or
      were euthanized for noncardiac causes. Kaplan-Meier analysis showed a median
      survival time of 8.3 mo. This is the first study to describe the clinical
      characteristics of a population of English bulldogs with presumed ARVC. Further
      studies are needed to better characterize the clinical features of the disease in
      this breed.

PMID- 29372872
TI  - Preventing "Flat-headed" Babies: A Commentary on "Impact of Parent Practices of
      Infant Positioning on Head Orientation Profile and Development of Positional
      Plagiocephaly in Healthy Term Infants".

PMID- 29372873
TI  - A novel mesial temporal stereotactic coordinate system.
AB  - OBJECTIVE Stereotactic laser ablation and neurostimulator placement represent an
      evolution in staged surgical intervention for epilepsy. As this practice evolves,
      optimal targeting will require standardized outcome measures that compare
      electrode lead or laser source with postprocedural changes in seizure frequency.
      The authors propose and present a novel stereotactic coordinate system based on
      mesial temporal anatomical landmarks to facilitate the planning and delineation
      of outcomes based on extent of ablation or region of stimulation within mesial
      temporal structures. METHODS The body of the hippocampus contains a natural axis,
      approximated by the interface of cornu ammonis area 4 and the dentate gyrus. The
      uncal recess of the lateral ventricle acts as a landmark to characterize the
      anterior-posterior extent of this axis. Several volumetric rotations are
      quantified for alignment with the mesial temporal coordinate system. First, the
      brain volume is rotated to align with standard anterior commissure-posterior
      commissure (AC-PC) space. Then, it is rotated through the axial and sagittal
      angles that the hippocampal axis makes with the AC-PC line. RESULTS Using this
      coordinate system, customized MATLAB software was developed to allow for
      intuitive standardization of targeting and interpretation. The angle between the
      AC-PC line and the hippocampal axis was found to be approximately 20 degrees -30
      degrees  when viewed sagittally and approximately 5 degrees -10 degrees  when
      viewed axially. Implanted electrodes can then be identified from CT in this
      space, and laser tip position and burn geometry can be calculated based on the
      intraoperative and postoperative MRI. CONCLUSIONS With the advent of stereotactic
      surgery for mesial temporal targets, a mesial temporal stereotactic system is
      introduced that may facilitate operative planning, improve surgical outcomes, and
      standardize outcome assessment.

PMID- 29372874
TI  - Letter to the Editor. Is there any relationship between estrogen
      receptor/progesterone receptor status and recurrence of meningioma?

PMID- 29372875
TI  - Cushing, Penfield, and cortical stimulation.
AB  - Harvey Cushing and Wilder Penfield enjoyed a unique professional and personal
      relationship. Shortly before his retirement from Harvard University in 1933,
      Cushing sent Penfield 8 sketches that he drew in 1902 and 1903 while he was at
      Johns Hopkins Hospital. The first series of 3 sketches illustrate the
      relationship between a cortical hemorrhagic lesion and the motor strip in a
      patient with focal motor seizures. The second series also comprises 3 sketches.
      These depict the operative findings in a patient in whom Cushing had electrically
      stimulated the precentral gyrus, before resecting the cortex subserving motility
      of the upper extremity to control painful dyskinetic movements. The third series
      consists of 2 sketches that illustrate the results of stimulation of the motor
      strip as an aid in the safe resection of an epileptogenic focus in a patient with
      Jacksonian seizures. These sketches are the subjects of this paper. They add to
      the relatively sparse record of Cushing's activities in cortical stimulation and
      in the treatment of functional disorders.

PMID- 29372876
TI  - The impact of spine disease, relative to cranial disease, on perception of health
      and care experience: an analysis of 1484 patients in a tertiary center.
AB  - OBJECTIVE Patient-reported outcomes have been increasingly mandated by regulators
      and payers to evaluate hospital and physician performance. The purpose of this
      study is to delineate the differences in patient-reported experience of hospital
      care for cranial and spinal operations. METHODS The authors selected all patients
      who underwent inpatient, elective cranial or spinal procedures and completed the
      Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey
      at a single, high-volume, tertiary care institution between October 2012 and
      September 2015. The association of the surgical procedure and diagnosis with
      various HCAHPS composite measures, calculated across 9 domains using standard top
      box methodology, was investigated. Multivariable logistic regression models were
      fitted for outcomes that were significant with procedure type and diagnosis group
      on univariate analysis, adjusting for age, sex, case complexity, overall health
      rating, and education level. RESULTS A total of 1484 patients met criteria and
      returned an HCAHPS survey. Overall, patients undergoing a cranial procedure gave
      top-box (most favorable) scores more often in pain management measure (66.3% vs
      59.6%, p = 0.01) compared with those undergoing spine surgery. Furthermore,
      despite better discharge scores (93.1% vs 87.1%, p < 0.001), spinal patients were
      less likely to report excellent health (7.4% vs 12.7%). Lastly, patients with a
      primary diagnosis of brain or spinal tumor compared with those with degenerative
      spinal disease and those with other neurosurgical diagnoses provided top-box
      scores more often regarding communication with doctors (82.7% vs 76.4% vs 75.2%,
      p = 0.04), pain management (71.8% vs 60.9% vs 59.1%, p = 0.002), and global
      rating (90.4% vs 84.0% vs 87.3%, p = 0.02). On multivariable analysis, spinal
      patients had significantly lower odds of reporting top-box scores in pain
      management (OR 0.67, 95% CI 0.52-0.85; p = 0.001), staff responsiveness (OR 0.68,
      95% CI 0.53-0.87; p = 0.002), and global rating (OR 0.59, 95% CI 0.42-0.82; p =
      0.002), and significantly higher odds of top-box scoring in discharge information
      (OR 2.15, 95% CI 1.45-3.18; p < 0.001) than cranial patients. Similarly, brain
      tumor cases were associated with significantly higher odds of top-box scoring in
      communication with doctors (OR 1.46, 95% CI 1.01-2.12; p = 0.04), pain management
      (OR 1.81, 95% CI 1.29-2.55; p < 0.001), staff responsiveness (OR 1.88, 95% CI
      1.33-2.66; p < 0.001), and global rating (OR 2.00, 95% CI 1.26-3.17; p = 0.003)
      compared with degenerative spine cases. CONCLUSIONS Significant differences in
      patient-reported experience with hospital care exist across different cranial and
      spine surgery patient populations. Overall, spinal patients, particularly those
      with degenerative spine disease, rated their health and their hospital experience
      lower relative to cranial patients. Identifying weaker areas of hospital
      performance in target populations can stimulate quality initiatives that aim to
      increase the overall hospital score.

PMID- 29372877
TI  - Early nerve repair in traumatic brachial plexus injuries in adults: treatment
      algorithm and first experiences.
AB  - OBJECTIVE The object of this study was to assess the advantages and disadvantages
      of early nerve repair within 2 weeks following adult traumatic brachial plexus
      injury (ATBPI). METHODS From 2009 onwards, the authors have strived to repair as
      early as possible extended C-5 to C-8 or T-1 lesions or complete loss of C-5 to C
      6 or C-7 function in patients in whom there was clinical and radiological
      suspicion of root avulsion. Among a group of 36 patients surgically treated in
      the period between 2009 and 2011, surgical findings in those who had undergone
      treatment within 2 weeks after trauma were retrospectively compared with results
      in those who had undergone delayed treatment. The result of biceps muscle
      reanimation was the primary outcome measure. RESULTS Five of the 36 patients were
      referred within 2 weeks after trauma and were eligible for early surgery. Nerve
      ruptures and/or avulsions were found in all early cases of surgery. The
      advantages of early surgery are as follows: no scar formation, easy anatomical
      identification, and gap length reduction. Disadvantages include less-clear
      demarcation of vital nerve tissue and unfamiliarity with the interpretation of
      frozen-section examination findings. All 5 early-treatment patients recovered a
      biceps force rated Medical Research Council grade 4. CONCLUSIONS Preliminary
      results of nerve repair within 2 weeks of ATBPI are encouraging, and the benefits
      outweigh the drawbacks. The authors propose a decision algorithm to select
      patients eligible for early surgery. Referral standards for patients with ATBPI
      must be adapted to enable early surgery.

PMID- 29372878
TI  - The transperiosteal "inside-out" occipital artery harvesting technique.
AB  - OBJECTIVE The occipital artery (OA) is a frequently used donor vessel for
      posterior circulation bypass procedures due to its proximity to the recipient
      vessels and its optimal caliber, length, and flow rate. However, its tortuous
      course through multiple layers of suboccipital muscles necessitates layer-by
      layer dissection. The authors of this cadaveric study aimed to describe a
      landmark-based novel anterograde approach to harvest OA in a proximal-to-distal
      "inside-out" fashion, which avoids multilayer dissection. METHODS Sixteen
      cadaveric specimens were prepared for surgical simulation, and the OA was
      harvested using the classic (n = 2) and novel (n = 14) techniques. The specimens
      were positioned three-quarters prone, with 45 degrees  contralateral head
      rotation. An inverted hockey-stick incision was made from the spinous process of
      C-2 to the mastoid tip, and the distal part of the OA was divided to lift up a
      myocutaneous flap, including the nuchal muscles. The OA was identified using the
      occipital groove (OG), the digastric muscle (DM) and its groove (DG), and the
      superior oblique muscle (SOM) as key landmarks. The OA was harvested
      anterogradely from the OG and within the flap until the skin incision was reached
      (proximal-to-distal technique). In addition, 35 dry skulls were assessed
      bilaterally (n = 70) to study additional craniometric landmarks to infer the
      course of the OA in the OG. RESULTS The OA was consistently found running in the
      OG, which was found between the posterior belly of the DM and the SOM. The mean
      total length of the mobilized OA was 12.8 +/- 1.2 cm, with a diameter of 1.3 +/-
      0.1 mm at the suboccipital segment and 1.1 +/- 0.1 mm at the skin incision. On
      dry skulls, the occipitomastoid suture (OMS) was found to be medial to the OG in
      the majority of the cases (68.6%), making it a useful landmark to locate the OG
      and thus the proximal OA. CONCLUSIONS The anterograde transperiosteal inside-out
      approach for harvesting the OA is a fast and easy technique. It requires only
      superficial dissection because the OA is found directly under the periosteum
      throughout its course, obviating tedious layer-by-layer muscle dissection. This
      approach avoids critical neurovascular structures like the vertebral artery. The
      key landmarks needed to localize the OA using this technique include the OMS, OG,
      DM and DG, and SOM.

PMID- 29372879
TI  - Microsurgical clipping of ophthalmic artery aneurysms: surgical results and
      visual outcomes with 208 aneurysms.
AB  - OBJECTIVE While most paraclinoid aneurysms can be clipped with excellent results,
      new postoperative visual deficits are a concern. New technology, including flow
      diverters, has increased the popularity of endovascular therapy. However,
      endovascular treatment of paraclinoid aneurysms is not without procedural risks,
      is associated with higher rates of incomplete aneurysm occlusion and recurrence,
      and may not address optic nerve compression symptoms that surgical debulking can.
      The increasing endovascular management of paraclinoid aneurysms should be
      justified by comparisons to surgical benchmarks. The authors, therefore,
      undertook this study to define patient, visual, and aneurysm outcomes in the most
      common type of paraclinoid aneurysm: ophthalmic artery (OphA) aneurysms. METHODS
      Results from microsurgical clipping of 208 OphA aneurysms in 198 patients were
      retrospectively reviewed. Patient demographics, aneurysm morphology (size,
      calcification, etc.), clinical characteristics, and patient outcomes were
      recorded and analyzed. RESULTS Despite 20% of these aneurysms being large or
      giant in size, complete aneurysm occlusion was accomplished in 91% of 208 cases,
      with OphA patency preserved in 99.5%. The aneurysm recurrence rate was 3.1% and
      the retreatment rate was 0%. Good outcomes (modified Rankin Scale score 0-2) were
      observed in 96.2% of patients overall and in all 156 patients with unruptured
      aneurysms. New visual field defects (hemianopsia or quadrantanopsia) were
      observed in 8 patients (3.8%), decreased visual acuity in 5 (2.4%), and monocular
      blindness in 9 (4.3%). Vision improved in 9 (52.9%) of the 17 patients with
      preoperative visual deficits. CONCLUSIONS The most important risk associated with
      clipping OphA aneurysms is a new visual deficit. Meticulous microsurgical
      technique is necessary during anterior clinoidectomy, aneurysm dissection, and
      clip application to optimize visual outcomes, and aggressive medical management
      postoperatively might potentially decrease the incidence of delayed visual
      deficits. As the results of endovascular therapy and specifically flow diverters
      become known, they warrant comparison with these surgical benchmarks to determine
      best practices.

PMID- 29372880
TI  - Deep brain stimulation outcomes in patients implanted under general anesthesia
      with frame-based stereotaxy and intraoperative MRI.
AB  - OBJECTIVE The authors' aim in this study was to evaluate placement accuracy and
      clinical outcomes in patients who underwent implantation of deep brain
      stimulation devices with the aid of frame-based stereotaxy and intraoperative MRI
      after induction of general anesthesia. METHODS Thirty-three patients with
      movement disorders (27 with Parkinson's disease) underwent implantation of
      unilateral or bilateral deep brain stimulation systems (64 leads total). All
      patients underwent the implantation procedure with standard frame-based
      techniques under general anesthesia and without microelectrode recording. MR
      images were acquired immediately after the procedure and fused to the
      preoperative plan to verify accuracy. To evaluate clinical outcome, different
      scales were used to assess quality of life (EQ-5D), activities of daily living
      (Unified Parkinson's Disease Rating Scale [UPDRS] part II), and motor function
      (UPDRS part III during off- and on-medication and off- and on-stimulation
      states). Accuracy was assessed by comparing the coordinates (x, y, and z) from
      the preoperative plan and coordinates from the tip of the lead on intraoperative
      MRI and postoperative CT scans. RESULTS The EQ-5D score improved or remained
      stable in 71% of the patients. When in the off-medication/on-stimulation state,
      all patients reported significant improvement in UPDRS III score at the last
      follow-up (p < 0.001), with a reduction of 25.2 points (46.3%) (SD 14.7 points
      and 23.5%, respectively). There was improvement or stability in the UPDRS II
      scores for 68% of the Parkinson's patients. For 2 patients, the stereotactic
      error was deemed significant based on intraoperative MRI findings. In these
      patients, the lead was removed and replaced after correcting for the error during
      the same procedure. Postoperative lead revision was not necessary in any of the
      patients. Based on findings from the last intraoperative MRI study, the mean
      difference between the tip of the electrode and the planned target was 0.82 mm
      (SD 0.5 mm, p = 0.006) for the x-axis, 0.67 mm (SD 0.5 mm, p < 0.001) for the y
      axis, and 0.78 mm (SD 0.7 mm, p = 0.008) for the z-axis. On average, the
      euclidian distance was 1.52 mm (SD 0.6 mm). In patients who underwent bilateral
      implantation, accuracy was further evaluated comparing the first implanted side
      and the second implanted side. There was a significant mediolateral (x-axis)
      difference (p = 0.02) in lead accuracy between the first (mean 1.02 mm, SD 0.57
      mm) and the second (mean 0.66 mm, SD 0.50 mm) sides. However, no significant
      difference was found for the y- and z-axes (p = 0.10 and p = 0.89, respectively).
      CONCLUSIONS Frame-based DBS implantation under general anesthesia with
      intraoperative MRI verification of lead location is safe, accurate, precise, and
      effective compared with standard implantation performed using awake
      intraoperative physiology. More clinical trials are necessary to directly compare
      outcomes of each technique.

PMID- 29372881
TI  - Clinical outcomes of intracranial solitary fibrous tumor and hemangiopericytoma:
      analysis according to the 2016 WHO classification of central nervous system
      tumors.
AB  - OBJECTIVE The authors conducted this retrospective study to investigate the
      clinical outcomes of intracranial solitary fibrous tumor (SFT) and
      hemangiopericytoma (HPC), defined according to the 2016 WHO classification of
      central nervous system (CNS) tumors. METHODS Histopathologically proven
      intracranial SFT and HPC cases treated in the period from June 1996 to September
      2014 were retrospectively reviewed and analyzed. Two neuropathologists reviewed
      pathological slides and regraded the specimens according to the 2016 WHO
      classification. Factors associated with progression-free survival (PFS) and
      overall survival (OS) were statistically evaluated with uni- and multivariate
      analyses. RESULTS The records of 47 patients-10 with SFT, 33 with HPC, and 4 with
      anaplastic HPC-were reviewed. A malignant transition from conventional SFT to WHO
      grade III SFT/HPC was observed in 2 cases, and 13 HPC cases were assigned grade
      III SFT/HPC. Mean and median follow-ups were 114.6 and 94.7 months, respectively
      (range 7.1-366.7 months). Gross-total resection (GTR) was significantly
      associated with longer PFS and OS (p = 0.012 for both), and adjuvant radiation
      therapy versus no such therapy led to significantly longer PFS (p = 0.018).
      Extracranial metastases to the liver, bone, lung, spine, and kidney occurred in
      10 patients (21.3%). Grade III SFT/HPC was strongly correlated with the
      development of extracranial metastases (p = 0.031). CONCLUSIONS The 2016 WHO
      classification of CNS tumors reflected the different types of pathological
      malignant progression and clinical outcomes better than prior classifications.
      Gross-total resection should be the primary treatment goal in patients with
      SFT/HPC, regardless of the pathological grade, and radiation can be administered
      as adjuvant therapy for patients with SFT/HPC that shows an aggressive phenotype
      or that is not treated with GTR.

PMID- 29372882
TI  - Validation of a neurovascular comorbidities index for retrospective database
      analysis.
AB  - OBJECTIVE Comorbidities have a significant effect on patient outcomes. Accounting
      for this effect is especially important in retrospective reviews of large
      databases; overpowered studies are at risk for finding significant results
      because of inaccurate patient risk stratification. The authors previously created
      a neurovascular comorbidities index (NCI) for patients with an unruptured
      intracranial aneurysm and found that the model's ability to predict patient
      outcomes was statistically significantly improved over that of the routinely used
      Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). In this
      study, the authors aimed to validate use of the NCI over that of the CCI and ECI
      for risk stratification of patients with other neurovascular diseases. METHODS
      The authors queried the National (Nationwide) Inpatient Sample database for the
      years 2002-2012 to compare the accuracy of the previously validated NCI with that
      of the CCI and ECI with respect to predicting outcomes for patients who had an
      arteriovenous malformation, a ruptured intracranial aneurysm, carotid artery
      stenosis, or dural arteriovenous fistula and who underwent surgical intervention.
      RESULTS For patients with an arteriovenous malformation, the NCI outperformed the
      CCI and ECI in predicting poor outcome, hospital length of stay (LOS), and total
      cost but was equivalent to the CCI in predicting death. For patients with a
      ruptured intracranial aneurysm, the NCI outperformed the ECI and CCI in
      predicting death, poor outcome, LOS, and total cost. For patients with carotid
      artery stenosis, the NCI outperformed the ECI and CCI in predicting LOS, but it
      was equivalent to the ECI in predicting death and total cost and inferior to the
      CCI in predicting poor outcome (p < 0.002 for all). An insufficient number of
      patients with dural arteriovenous fistula who underwent surgical intervention
      were available for analysis (n < 10), and they therefore were excluded from
      study. For 11 of 12 metrics, the NCI was the significantly more efficient model.
      CONCLUSIONS The NCI outperforms the CCI and ECI by providing more appropriate and
      efficient risk stratification of patients regarding death, outcome, LOS, and
      cost. Given this finding, the NCI should be used for retrospective reviews of
      patient outcomes instead of the CCI or ECI.

PMID- 29372883
TI  - Brain repair by hematopoietic growth factors in the subacute phase of traumatic
      brain injury.
AB  - OBJECTIVE Traumatic brain injury (TBI) is a major cause of long-term disability
      and death in young adults. The lack of pharmaceutical therapy for post-acute TBI
      recovery remains a crucial medical challenge. Stem cell factor (SCF) and
      granulocyte colony-stimulating factor (G-CSF), which are 2 key hematopoietic
      growth factors, have shown neuroprotective and neurorestorative effects in
      experimental stroke. The objective of this study was to determine the therapeutic
      efficacy of combined treatment (SCF + G-CSF) in subacute TBI. METHODS Young-adult
      male C57BL mice were subject to TBI in the cortex of the right hemisphere. After
      TBI induction, mice were randomly divided into 2 groups: a vehicle control group
      and an SCF + G-CSF treatment group. Mice without TBI served as sham operative
      controls. Treatment was initiated 2 weeks after TBI induction. SCF (200 MUg/kg)
      and G-CSF (50 MUg/kg) or an equal volume of vehicle solution was subcutaneously
      injected daily for 7 days. A battery of neurobehavioral tests for evaluation of
      memory and cognitive function (water maze and novel object recognition tests),
      anxiety (elevated plus maze test), and motor function (Rota-Rod test) was
      performed during the period of 2-9 weeks after treatment. Neurodegeneration and
      dendritic density in both hemispheres were determined through histochemistry and
      immunohistochemistry at 11 weeks posttreatment. RESULTS Water maze testing showed
      that TBI-impaired spatial learning and memory was restored by SCF + G-CSF
      treatment. The findings from the elevated plus maze tests revealed that SCF + G
      CSF treatment recovered TBI-caused anxiety and risk-taking behavior. There were
      no significant differences between the treated and nontreated TBI mice in both
      the Rota-Rod test and novel object recognition test. In the brain sections, the
      authors observed that widespread degenerating neurons were significantly
      increased in both hemispheres in the TBI-vehicle control mice. TBI-induced
      increases in neurodegeneration were significantly reduced by SCF + G-CSF
      treatment in the contralateral hemisphere, making it no different from that of
      the sham controls. Dendritic density in the frontal cortex of the contralateral
      hemisphere was significantly reduced in the TBI-vehicle control mice, whereas SCF
      + G-CSF-treated TBI mice showed significant increases of the dendritic density in
      the same brain region. SCF + G-CSF-treated TBI mice also showed a trend toward
      increasing dendritic density in the contralateral hippocampus. CONCLUSIONS SCF +
      G-CSF treatment in the subacute phase of TBI restored TBI-impaired spatial
      learning and memory, prevented posttraumatic anxiety and risk-taking behavior,
      inhibited TBI-induced neurodegeneration, and enhanced neural network remodeling.
      These findings suggest the therapeutic potential of hematopoietic growth factors
      for brain repair in the subacute phase of TBI.

PMID- 29372884
TI  - Volumetric changes and clinical outcome for petroclival meningiomas after primary
      treatment with Gamma Knife radiosurgery.
AB  - OBJECTIVE Petroclival meningiomas (PCMs) can cause devastating clinical symptoms
      due to mass effect on cranial nerves (CNs); thus, patients harboring these tumors
      need treatment. Many neurosurgeons advocate for microsurgery because removal of
      the tumor can provide relief or result in symptom disappearance. Gamma Knife
      radiosurgery (GKRS) is often an alternative for surgery because it can cause
      tumor shrinkage with improvement of symptoms. This study evaluates qualitative
      volumetric changes of PCM after primary GKRS and its impact on clinical symptoms.
      METHODS The authors performed a retrospective study of patients with PCM who
      underwent primary GKRS between 2003 and 2015 at the Gamma Knife Center of the
      Elisabeth-Tweesteden Hospital in Tilburg, the Netherlands. This study yields 53
      patients. In this study the authors concentrate on qualitative volumetric tumor
      changes, local tumor control rate, and the effect of the treatment on trigeminal
      neuralgia (TN). RESULTS Local tumor control was 98% at 5 years and 93% at 7 years
      (Kaplan-Meier estimates). More than 90% of the tumors showed regression in volume
      during the first 5 years. The mean volumetric tumor decrease was 21.2%, 27.1%,
      and 31% at 1, 3, and 6 years of follow-up, respectively. Improvement in TN was
      achieved in 61%, 67%, and 70% of the cases at 1, 2, and 3 years of follow-up,
      respectively. This was associated with a mean volumetric tumor decrease of 25% at
      the 1-year follow-up to 32% at the 3-year follow-up. CONCLUSIONS GKRS for PCMs
      yields a high tumor control rate with a low incidence of neurological deficits.
      Many patients with TN due to PCM experienced improvement in TN after
      radiosurgery. GKRS achieves significant volumetric tumor decrease in the first
      years of follow-up and thereafter.

PMID- 29372885
TI  - Immune response after a single intravenous peramivir administration in children
      with influenza.
AB  - BACKGROUND: Immune response after intravenous peramivir administration, which is
      approved for children with influenza infection in Japan, is unclear. METHODS:
      Kinetics of viral load and serum cytokine levels before and after peramivir
      therapy were analysed in 17 and 8 hospitalized children infected with influenza A
      and B, respectively. Additionally, haemagglutination inhibition (HI) titre was
      measured. The first day of hospital admission was defined as day 0. RESULTS:
      Serum interleukin (IL)-6 levels in influenza-A-infected children significantly
      decreased after peramivir administration, unlike in those with influenza B where
      a decrease on day 1 was followed by an increase on day 2. Serum IL-6 kinetics
      were similar to viral load kinetics in both influenza-A- and B-infected children
      between days 0 and 2. Serum IL-8 levels gradually decreased after peramivir
      therapy in influenza-A-infected children but increased between days 1 and 2 in
      influenza-B-infected children. Conversely, serum IL-10 levels gradually decreased
      over time. Serum interferon-gamma and granulocyte macrophage colony-stimulating
      factor levels remained low until day 5. Day 0-4 serum HI titres were <4-fold in
      all children infected with influenza A or B. Additionally, day 5 HI titres were
      positive in 4 of 6 influenza A cases and all 3 influenza B cases. CONCLUSIONS:
      Our results suggest that viral load and inflammatory cytokine kinetics were
      associated with the antiviral therapy used and that second peramivir
      administration should be considered in influenza B. The results also highlight
      antiviral agents as key determinants of the clinical course of influenza virus
      infection in children.

PMID- 29372886
TI  - The outcome of HIV-positive late presenters according to detectable CMV DNA and
      anti-CMV treatment.
AB  - BACKGROUND: HIV late presenters are at high risk of cytomegalovirus (CMV)
      reactivation and end-organ disease. CMV viraemia has been associated with poor
      survival but the effect of anti-CMV treatment has not been studied in this
      setting. METHODS: HIV-positive patients were included in a retrospective study if
      presenting with <350 CD4+ T-cells/MUl and starting an antiretroviral treatment
      within 3 months of the diagnosis. Primary end point was 5-year survival according
      to the presence of CMV viraemia, CMV end-organ disease and anti-CMV treatment.
      RESULTS: 302 patients were included. 157 patients (52%) presented CMV viraemia
      (CMV-V) and 44 (14.6%) CMV end-organ disease (CMV-EOD). 5-year mortality was
      higher in CMV-EOD and CMV-V patients than in CMV-negative patients (11.4 versus
      9.6 versus 0%; P=0.002). In patients with CMV-V, 5-year mortality was numerically
      higher in untreated patients (12.9% versus 6.9%; P=0.257) without reaching
      statistical significance. At univariate analysis the diagnosis of serious
      opportunistic infections (cryptococcosis, progressive multifocal
      leukoencephalopathy, lymphoma; P=0.001) and the absence of a negative CMV DNA in
      the follow-up (P<0.001) were associated with poor outcome. At multivariate
      analysis HCV coinfection (P=0.016; aOR 6.98, 95% CI 1.50, 32.59), the absence of
      a negative CMV DNA in the follow-up (P<0.001; aOR 19.40, 95% CI 3.70, 101.64) and
      marginally the absence of anti-CMV treatment (P=0.052; aOR 4.944, 95% CI 0.99,
      24.73) were independent predictors of poor outcome. CONCLUSIONS: CMV reactivation
      in HIV-positive patients with poor immunity is associated with worse prognosis:
      the pre-emptive use of anti-CMV therapy was associated with a better outcome in
      patients with CMV-V.

PMID- 29372887
TI  - NRAM: a disruptive carbon-nanotube resistance-change memory.
AB  - Advanced memory technology based on carbon nanotubes (CNTs) (NRAM) possesses
      desired properties for implementation in a host of integrated systems due to
      demonstrated advantages of its operation including high speed (nanotubes can
      switch state in picoseconds), high endurance (over a trillion), and low power
      (with essential zero standby power). The applicable integrated systems for NRAM
      have markets that will see compound annual growth rates (CAGR) of over 62%
      between 2018 and 2023, with an embedded systems CAGR of 115% in 2018-2023
      (http://bccresearch.com/pressroom/smc/bcc-research-predicts:-nram-(finally)-to
      revolutionize-computer-memory). These opportunities are helping drive the
      realization of a shift from silicon-based to carbon-based (NRAM) memories. NRAM
      is a memory cell made up of an interlocking matrix of CNTs, either touching or
      slightly separated, leading to low or higher resistance states respectively. The
      small movement of atoms, as opposed to moving electrons for traditional silicon
      based memories, renders NRAM with a more robust endurance and high temperature
      retention/operation which, along with high speed/low power, is expected to
      blossom in this memory technology to be a disruptive replacement for the current
      status quo of DRAM (dynamic RAM), SRAM (static RAM), and NAND flash memories.

PMID- 29372888
TI  - Effects of flexibility and aspect ratio on the aerodynamic performance of
      flapping wings.
AB  - In the current study, we experimentally investigated the flexibility effects on
      the aerodynamic performance of flapping wings and the correlation with aspect
      ratio at angle of attack alpha  =  45 degrees . The Reynolds number based on the
      chord length and the wing tip velocity is maintained at Re  =  5.3  *  103. Our
      result for compliant wings with an aspect ratio of 4 shows that wing flexibility
      can offer improved aerodynamic performance compared to that of a rigid wing.
      Flexible wings are found to offer higher lift-to-drag ratios; in particular,
      there is significant reduction in drag with little compromise in lift. The
      mechanism of the flexibility effects on the aerodynamic performance is addressed
      by quantifying the aerodynamic lift and drag forces, the transverse displacement
      on the wings and the flow field around the wings. The regime of the effective
      stiffness that offers improved aerodynamic performance is quantified in a range
      of about 0.5-10 and it matches the stiffness of insect wings with similar aspect
      ratios. Furthermore, we find that the aspect ratio of the wing is the predominant
      parameter determining the flexibility effects of compliant wings. Compliant wings
      with an aspect ratio of two do not demonstrate improved performance compared to
      their rigid counterparts throughout the entire stiffness regime investigated. The
      correlation between wing flexibility effects and the aspect ratio is supported by
      the stiffness of real insect wings.

PMID- 29372889
TI  - Hydrogenated TiO2 nanotube photonic crystals for enhanced photoelectrochemical
      water splitting.
AB  - We report the design, fabrication and characterization of novel TiO2 nanotube
      photonic crystals with a crystalline core/disordered shell structure as well as
      substantial oxygen vacancies for photoelectrochemical (PEC) water splitting. The
      novel TiO2 nanotube photonic crystals are fabricated by annealing of anodized
      TiO2 nanotube photonic crystals in hydrogen atmosphere at various temperatures.
      The optimized novel TiO2 nanotube photonic crystals produce a maximal
      photocurrent density of 2.2 mA cm-2 at 0.22 V versus Ag/AgCl, which is two times
      higher that of the TiO2 nanotube photonic crystals annealed in air. Such
      significant PEC performance improvement can be ascribed to synergistic effects of
      the disordered surface layer and oxygen vacancies. The reduced band gap owing to
      the disordered surface layer and localized states induced by oxygen vacancies can
      enhance the efficient utilization of visible light. In addition, the disordered
      surface layer and substantial oxygen vacancies can promote the efficiency for
      separation and transport of the photogenerated carriers. This work may open up
      new opportunities for the design and construction of the high efficient and low
      cost PEC water splitting system.

PMID- 29372890
TI  - Reactive molecular dynamics simulations of the mechanical properties of various
      phosphorene allotropes.
AB  - Although various phosphorene allotropes have been theoretically predicted to be
      stable at 0 K, the mechanical properties and fracture mechanism at room
      temperature remain unclear for many of them. We investigate through reactive
      molecular dynamics simulations at room temperature the mechanical properties of
      phosphorene allotropes including: five sheets with hexagonal structures (beta-,
      gamma-, delta-, theta-, and alpha-phosphorene), one sheet with 4-8 membered rings
      (4-8-P), and two sheets with 5-7 membered rings. High, moderate and slight
      anisotropies in their mechanical properties are observed, depending on their
      crystal structures. Their Young's moduli and tensile strength are approximately
      in the range from 7.3% through 25%, and from 8.6% through 22% of those of
      graphene, respectively. At the early stage of fracture, eye-shaped cracks are
      formed by local bond breaking and perpendicular to the tensile direction in
      hexagonal and 4-8-P sheets. Complete fractures take place with straight cracks in
      these hexagonal sheets under tension along the zigzag direction and under tension
      along the square edge direction in the 4-8-P sheet. Crack meandering and
      branching are observed during the tension of alpha-, beta-, and gamma-phosphorene
      along the armchair direction; and along the square diagonal direction in the 4-8
      P sheet. Under uniaxial tension of two phosphorene sheets with 5-7 atom rings, 12
      and 10 membered rings are formed by merging two neighbor heptagons, and a
      heptagon and its neighbor pentagon, respectively. These 12 and 10 membered rings
      coalesce subsequently, causing the failure of these two sheets. The results are
      of great importance in the design of these novel phosphorene allotropes.

PMID- 29372891
TI  - Lithium effects on the mechanical and electronic properties of germanium
      nanowires.
AB  - Semiconductor nanowire arrays promise rapid development of a new generation of
      lithium (Li) batteries because they can store more Li atoms than conventional
      crystals due to their large surface areas. During the charge-discharge process,
      the electrodes experience internal stresses that fatigue the material and limit
      the useful life of the battery. The theoretical study of electronic and
      mechanical properties of lithiated nanowire arrays allows the designing of
      electrode materials that could improve battery performance. In this work, we
      present a density functional theory study of the electronic band structure,
      formation energy, binding energy, and Young's modulus (Y) of hydrogen passivated
      germanium nanowires (H-GeNWs) grown along the [111] and [001] crystallographic
      directions with surface and interstitial Li atoms. The results show that the
      germanium nanowires (GeNWs) with surface Li atoms maintain their semiconducting
      behavior but their energy gap size decreases when the Li concentration grows. In
      contrast, the GeNWs can have semiconductor or metallic behavior depending on the
      concentration of the interstitial Li atoms. On the other hand, Y is an indicator
      of the structural changes that GeNWs suffer due to the concentration of Li atoms.
      For surface Li atoms, Y stays almost constant, whereas for interstitial Li atoms,
      the Y values indicate important structural changes in the GeNWs.

PMID- 29372892
TI  - Titanium contacts to graphene: process-induced variability in electronic and
      thermal transport.
AB  - Contact resistance (R C) is a major limiting factor in the performance of
      graphene devices. R C is sensitive to the quality of the interface and the
      composition of the contact, which are affected by the graphene transfer process
      and contact deposition conditions. In this work, a linear correlation is observed
      between the composition of Ti contacts, characterized by x-ray photoelectron
      spectroscopy, and the Ti/graphene contact resistance measured by the transfer
      length method. We find that contact composition is tunable via deposition rate
      and base pressure. Reactor base pressure is found to effect the resultant contact
      resistance. The effect of contact deposition conditions on thermal transport
      measured by time-domain thermoreflectance is also reported. Interfaces with
      higher oxide composition appear to result in a lower thermal boundary
      conductance. Possible origins of this thermal boundary conductance change with
      oxide composition are discussed.

PMID- 29372893
TI  - High-performance Cu nanoparticles/three-dimensional graphene/Ni foam hybrid for
      catalytic and sensing applications.
AB  - A novel hybrid of Cu nanoparticles/three-dimensional graphene/Ni foam (Cu
      NPs/3DGr/NiF) was prepared by chemical vapor deposition, followed by a galvanic
      displacement reaction in Ni- and Cu-ion-containing salt solution through a one
      step reaction. The as-prepared Cu NPs/3DGr/NiF hybrid is uniform, stable,
      recyclable and exhibits an extraordinarily high catalytic efficiency for the
      reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) with a reduction rate
      constant K = 0.056 15 s-1, required time ~30 s and excellent sensing properties
      for the non-enzymatic amperometric hydrogen peroxide (H2O2) with a linear range
      ~50 MUM-9.65 mM, response time ~3 s, detection limit ~1 MUM. The results indicate
      that the as-prepared Cu NPs/3DGr/NiF hybrid can be used to replace expensive
      noble metals in catalysis and sensing applications.

PMID- 29372895
TI  - The importance of the helical structure of a MamC-derived magnetite-interacting
      peptide for its function in magnetite formation.
AB  - Biomineralization is the process of mineral formation by organisms and involves
      the uptake of ions from the environment in order to produce minerals, with the
      process generally being mediated by proteins. Most proteins that are involved in
      mineral interactions are predicted to contain disordered regions containing large
      numbers of negatively charged amino acids. Magnetotactic bacteria, which are used
      as a model system for iron biomineralization, are Gram-negative bacteria that can
      navigate through geomagnetic fields using a specific organelle, the magnetosome.
      Each organelle comprises a membrane-enveloped magnetic nanoparticle, magnetite,
      the formation of which is controlled by a specific set of proteins. One of the
      most abundant of these proteins is MamC, a small magnetosome-associated integral
      membrane protein that contains two transmembrane alpha-helices connected by an
      ~21-amino-acid peptide. In vitro studies of this MamC peptide showed that it
      forms a helical structure that can interact with the magnetite surface and affect
      the size and shape of the growing crystal. Our results show that a disordered
      structure of the MamC magnetite-interacting component (MamC-MIC) abolishes its
      interaction with magnetite particles. Moreover, the size and shape of magnetite
      crystals grown in in vitro magnetite-precipitation experiments in the presence of
      this disordered peptide were different from the traits of crystals grown in the
      presence of other peptides or in the presence of the helical MIC. It is suggested
      that the helical structure of the MamC-MIC is important for its function during
      magnetite formation.

PMID- 29372894
TI  - Structure of Rubisco from Arabidopsis thaliana in complex with 2
      carboxyarabinitol-1,5-bisphosphate.
AB  - The crystal structure of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco) from Arabidopsis thaliana is reported at 1.5 A resolution. In light of
      the importance of A. thaliana as a model organism for understanding higher plant
      biology, and the pivotal role of Rubisco in photosynthetic carbon assimilation,
      there has been a notable absence of an A. thaliana Rubisco crystal structure. A.
      thaliana Rubisco is an L8S8 hexadecamer comprising eight plastome-encoded
      catalytic large (L) subunits and eight nuclear-encoded small (S) subunits. A.
      thaliana produces four distinct small-subunit isoforms (RbcS1A, RbcS1B, RbcS2B
      and RbcS3B), and this crystal structure provides a snapshot of A. thaliana
      Rubisco containing the low-abundance RbcS3B small-subunit isoform. Crystals were
      obtained in the presence of the transition-state analogue 2-carboxy-D-arabinitol
      1,5-bisphosphate. A. thaliana Rubisco shares the overall fold characteristic of
      higher plant Rubiscos, but exhibits an interesting disparity between sequence and
      structural relatedness to other Rubisco isoforms. These results provide the
      structural framework to understand A. thaliana Rubisco and the potential
      catalytic differences that could be conferred by alternative A. thaliana Rubisco
      small-subunit isoforms.

PMID- 29372896
TI  - Crystal structure of the outer membrane protein OmpU from Vibrio cholerae at 2.2
      A resolution.
AB  - Vibrio cholerae causes a severe disease that kills thousands of people annually.
      The outer membrane protein OmpU is the most abundant outer membrane protein in V.
      cholerae, and has been identified as an important virulence factor that is
      involved in host-cell interaction and recognition, as well as being critical for
      the survival of the pathogenic V. cholerae in the host body and in harsh
      environments. The mechanism of these processes is not well understood owing to a
      lack of the structure of V. cholerae OmpU. Here, the crystal structure of the V.
      cholerae OmpU trimer is reported to a resolution of 2.2 A. The protomer forms a
      16-beta-stranded barrel with a noncanonical N-terminal coil located in the lumen
      of the barrel that consists of residues Gly32-Ser42 and is observed to
      participate in forming the second gate in the pore. By mapping the published
      functional data onto the OmpU structure, the OmpU structure reinforces the notion
      that the long extracellular loop L4 with a beta-hairpin-like motif may be
      critical for host-cell binding and invasion, while L3, L4 and L8 are crucially
      implicated in phage recognition by V. cholerae.

PMID- 29372897
TI  - The deduced role of a chitinase containing two nonsynergistic catalytic domains.
AB  - The glycoside hydrolase family 18 chitinases degrade or alter chitin. Multiple
      catalytic domains in a glycoside hydrolase family 18 chitinase function
      synergistically during chitin degradation. Here, an insect group III chitinase
      from the agricultural pest Ostrinia furnacalis (OfChtIII) is revealed to be an
      arthropod-conserved chitinase that contains two nonsynergistic GH18 domains
      according to its catalytic properties. Both GH18 domains are active towards
      single-chained chitin substrates, but are inactive towards insoluble chitin
      substrates. The crystal structures of each unbound GH18 domain, as well as of
      GH18 domains complexed with hexa-N-acetyl-chitohexaose or penta-N-acetyl
      chitopentaose, suggest that the two GH18 domains possess endo-specific
      activities. Physiological data indicated that the developmental stage-dependent
      gene-expression pattern of OfChtIII was the same as that of the chitin synthase
      OfChsA but significantly different from that of the chitinase OfChtI, which is
      indispensable for cuticular chitin degradation. Additionally, immunological
      staining indicated that OfChtIII was co-localized with OfChsA. Thus, OfChtIII is
      most likely to be involved in the chitin-synthesis pathway.

PMID- 29372898
TI  - The folate-binding module of Thermus thermophilus cobalamin-dependent methionine
      synthase displays a distinct variation of the classical TIM barrel: a TIM barrel
      with a 'twist'.
AB  - Methyl transfer between methyltetrahydrofolate and corrinoid molecules is a key
      reaction in biology that is catalyzed by a number of enzymes in many prokaryotic
      and eukaryotic organisms. One classic example of such an enzyme is cobalamin
      dependent methionine synthase (MS). MS is a large modular protein that utilizes
      an SN2-type mechanism to catalyze the chemically challenging methyl transfer from
      the tertiary amine (N5) of methyltetrahydrofolate to homocysteine in order to
      form methionine. Despite over half a century of study, many questions remain
      about how folate-dependent methyltransferases, and MS in particular, function.
      Here, the structure of the folate-binding (Fol) domain of MS from Thermus
      thermophilus is reported in the presence and absence of methyltetrahydrofolate.
      It is found that the methyltetrahydrofolate-binding environment is similar to
      those of previously described methyltransferases, highlighting the conserved role
      of this domain in binding, and perhaps activating, the methyltetrahydrofolate
      substrate. These structural studies further reveal a new distinct and
      uncharacterized topology in the C-terminal region of MS Fol domains. Furthermore,
      it is found that in contrast to the canonical TIM-barrel beta8alpha8 fold found
      in all other folate-binding domains, MS Fol domains exhibit a unique beta8alpha7
      fold. It is posited that these structural differences are important for MS
      function.

PMID- 29372900
TI  - PRISM-EM: template interface-based modelling of multi-protein complexes guided by
      cryo-electron microscopy density maps. Corrigendum.
AB  - A revised Table 6 and Supporting Information are provided for the article by Kuzu
      et al. [(2016), Acta Cryst. D72, 1137-1148].

PMID- 29372899
TI  - A DNA structural alphabet provides new insight into DNA flexibility.
AB  - DNA is a structurally plastic molecule, and its biological function is enabled by
      adaptation to its binding partners. To identify the DNA structural polymorphisms
      that are possible in such adaptations, the dinucleotide structures of 60 000 DNA
      steps from sequentially nonredundant crystal structures were classified and an
      automated protocol assigning 44 distinct structural (conformational) classes
      called NtC (for Nucleotide Conformers) was developed. To further facilitate
      understanding of the DNA structure, the NtC were assembled into the DNA
      structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and the
      projection of CANA onto the graphical representation of the molecular structure
      was proposed. The NtC classification was used to define a validation score called
      confal, which quantifies the conformity between an analyzed structure and the
      geometries of NtC. NtC and CANA assignment were applied to analyze the structural
      properties of typical DNA structures such as Dickerson-Drew dodecamers, guanine
      quadruplexes and structural models based on fibre diffraction. NtC, CANA and
      confal assignment, which is accessible at the website https://dnatco.org, allows
      the quantitative assessment and validation of DNA structures and their subsequent
      analysis by means of pseudo-sequence alignment. An animated Interactive 3D
      Complement (I3DC) is available in Proteopedia at
      http://proteopedia.org/w/Journal:Acta_Cryst_D:2.

PMID- 29372901
TI  - The novel thermostable cellulose-degrading enzyme DtCel5H from Dictyoglomus
      thermophilum: crystallization and X-ray crystallographic analysis.
AB  - Cellulose-based products constitute the great majority of municipal waste, and
      applications of cellulases in the conversion of waste biomass to biofuels will be
      a key technology in future biorefineries. Currently, multi-enzymatic pre
      treatment of biomass is a crucial step in making carbohydrates more accessible
      for subsequent fermentation. Using bioinformatics analysis, endo-beta-(1,4)
      glucanase from Dictyoglomus thermophilum (DtCel5H) was identified as a new member
      of glycosyl hydrolase family 5. The gene encoding DtCel5H was cloned and the
      recombinant protein was overexpressed for crystallization and biophysical
      studies. Here, it is shown that this enzyme is active on cellulose substrates and
      is highly thermostable. Crystals suitable for crystallographic investigations
      were also obtained in different crystallization conditions. In particular,
      ordered crystals of DtCel5H were obtained using either ammonium sulfate or
      polyethylene glycol (PEG) as a precipitant agent. The crystals obtained in the
      presence of ammonium sulfate belonged to space group P32, with unit-cell
      parameters a = 73.1, b = 73.1, 73.1, c = 127.8 A, and diffracted to 1.5 A
      resolution, whereas the second crystal form belonged to the orthorhombic space
      group P212121, with unit-cell parameters a = 49.3, b = 67.9, c = 103.7 A, and
      diffracted to 1.6 A resolution. The crystal structure was solved in both space
      groups using molecular-replacement methods. Structure-activity and structure
      stability studies of DtCel5H will provide insights for the design of high
      performance enzymes.

PMID- 29372902
TI  - Crystal structure of cytoplasmic acetoacetyl-CoA thiolase from Saccharomyces
      cerevisiae.
AB  - Thiolases are vital enzymes which participate in both degradative and
      biosynthetic pathways. Biosynthetic thiolases catalyze carbon-carbon bond
      formation by a Claisen condensation reaction. The cytoplasmic acetoacetyl-CoA
      thiolase from Saccharomyces cerevisiae, ERG10, catalyses carbon-carbon bond
      formation in the mevalonate pathway. The structure of a S. cerevisiae
      biosynthetic thiolase has not previously been reported. Here, crystal structures
      of apo ERG10 and its Cys91Ala variant were solved at resolutions of 2.2 and 1.95
      A, respectively. The structure determined shows that ERG10 shares the
      characteristic thiolase superfamily fold, with a similar active-site architecture
      to those of type II thiolases and a similar binding pocket, apart from Ala159 at
      the entrance to the pantetheine-binding cavity, which appears to be a determinant
      of the poor binding ability of the substrate. Moreover, comparative binding
      pocket analysis of molecule B in the asymmetric unit of the apo structure with
      that of the CoA-bound complex of human mitochondrial acetoacetyl-CoA thiolase
      indicates the canonical binding mode of CoA. Furthermore, the steric hindrance
      revealed in a structural comparison of molecule A with the CoA-bound form raise
      the possibility of conformational changes that are associated with substrate
      binding.

PMID- 29372903
TI  - Structure of aspartate beta-semialdehyde dehydrogenase from Francisella
      tularensis.
AB  - Aspartate beta-semialdehyde dehydrogenase (ASADH) is an enzyme involved in the
      diaminopimelate pathway of lysine biosynthesis. It is essential for the viability
      of many pathogenic bacteria and therefore has been the subject of considerable
      research for the generation of novel antibiotic compounds. This manuscript
      describes the first structure of ASADH from Francisella tularensis, the causative
      agent of tularemia and a potential bioterrorism agent. The structure was
      determined at 2.45 A resolution and has a similar biological assembly to other
      bacterial homologs. ASADH is known to be dimeric in bacteria and have extensive
      interchain contacts, which are thought to create a half-sites reactivity enzyme.
      ASADH from higher organisms shows a tetrameric oligomerization, which also has
      implications for both reactivity and regulation. This work analyzes the apo form
      of F. tularensis ASADH, as well as the binding of the enzyme to its cofactor
      NADP+.

PMID- 29372904
TI  - Structure and stability of the Human respiratory syncytial virus M2-1 RNA-binding
      core domain reveals a compact and cooperative folding unit.
AB  - Human syncytial respiratory virus is a nonsegmented negative-strand RNA virus
      with serious implications for respiratory disease in infants, and has recently
      been reclassified into a new family, Pneumoviridae. One of the main reasons for
      this classification is the unique presence of a transcriptional antiterminator,
      called M2-1. The puzzling mechanism of action of M2-1, which is a rarity among
      antiterminators in viruses and is part of the RNA polymerase complex, relies on
      dissecting the structure and function of this multidomain tetramer. The RNA
      binding activity is located in a monomeric globular 'core' domain, a high
      resolution crystal structure of which is now presented. The structure reveals a
      compact domain which is superimposable on the full-length M2-1 tetramer, with
      additional electron density for the C-terminal tail that was not observed in the
      previous models. Moreover, its folding stability was determined through chemical
      denaturation, which shows that the secondary and tertiary structure unfold
      concomitantly, which is indicative of a two-state equilibrium. These results
      constitute a further step in the understanding of this unique RNA-binding domain,
      for which there is no sequence or structural counterpart outside this virus
      family, in addition to its implications in transcription regulation and its
      likeliness as an antiviral target.

PMID- 29372905
TI  - Production, biophysical characterization and initial crystallization studies of
      the N- and C-terminal domains of DsbD, an essential enzyme in Neisseria
      meningitidis.
AB  - The membrane protein DsbD is a reductase that acts as an electron hub,
      translocating reducing equivalents from cytoplasmic thioredoxin to a number of
      periplasmic substrates involved in oxidative protein folding, cytochrome c
      maturation and oxidative stress defence. DsbD is a multi-domain protein
      consisting of a transmembrane domain (t-DsbD) flanked by two periplasmic domains
      (n-DsbD and c-DsbD). Previous studies have shown that DsbD is required for the
      survival of the obligate human pathogen Neisseria meningitidis. To help
      understand the structural and functional aspects of N. meningitidis DsbD, the two
      periplasmic domains which are required for electron transfer are being studied.
      Here, the expression, purification and biophysical properties of n-NmDsbD and c
      NmDsbD are described. The crystallization and crystallographic analysis of n
      NmDsbD and c-NmDsbD are also described in both redox states, which differ only in
      the presence or absence of a disulfide bond but which crystallized in completely
      different conditions. Crystals of n-NmDsbDOx, n-NmDsbDRed, c-NmDsbDOx and c
      NmDsbDRed diffracted to 2.3, 1.6, 2.3 and 1.7 A resolution and belonged to space
      groups P213, P321, P41 and P1211, respectively.

PMID- 29372906
TI  - Structural characterization of a novel monotreme-specific protein with
      antimicrobial activity from the milk of the platypus.
AB  - Monotreme lactation protein (MLP) is a recently identified protein with
      antimicrobial activity. It is present in the milk of monotremes and is unique to
      this lineage. To characterize MLP and to gain insight into the potential role of
      this protein in the evolution of lactation, the crystal structure of duck-billed
      platypus (Ornithorhynchus anatinus) MLP was determined at 1.82 A resolution. This
      is the first structure to be reported for this novel, mammalian antibacterial
      protein. MLP was expressed as a FLAG epitope-tagged protein in mammalian cells
      and crystallized readily, with at least three space groups being observed (P1, C2
      and P21). A 1.82 A resolution native data set was collected from a crystal in
      space group P1, with unit-cell parameters a = 51.2, b = 59.7, c = 63.1 A, alpha =
      80.15, beta = 82.98, gamma = 89.27 degrees . The structure was solved by SAD
      phasing using a protein crystal derivatized with mercury in space group C2, with
      unit-cell parameters a = 92.7, b = 73.2, c = 56.5 A, beta = 90.28 degrees . MLP
      comprises a monomer of 12 helices and two short beta-strands, with much of the N
      terminus composed of loop regions. The crystal structure of MLP reveals no three
      dimensional similarity to any known structures and reveals a heretofore unseen
      fold, supporting the idea that monotremes may be a rich source for the
      identification of novel proteins. It is hypothesized that MLP in monotreme milk
      has evolved to specifically support the unusual lactation strategy of this
      lineage and may have played a central role in the evolution of these mammals.

PMID- 29372907
TI  - Solution NMR structures of oxidized and reduced Ehrlichia chaffeensis
      thioredoxin: NMR-invisible structure owing to backbone dynamics.
AB  - Thioredoxins are small ubiquitous proteins that participate in a diverse variety
      of redox reactions via the reversible oxidation of two cysteine thiol groups in a
      structurally conserved active site. Here, the NMR solution structures of a
      reduced and oxidized thioredoxin from Ehrlichia chaffeensis (Ec-Trx, ECH_0218),
      the etiological agent responsible for human monocytic ehrlichiosis, are
      described. The overall topology of the calculated structures is similar in both
      redox states and is similar to those of other thioredoxins: a five-stranded,
      mixed beta-sheet (beta1-beta3-beta2-beta4-beta5) surrounded by four alpha
      helices. Unlike other thioredoxins studied by NMR in both redox states, the 1H
      15N HSQC spectrum of reduced Ec-Trx was missing eight additional amide cross
      peaks relative to the spectrum of oxidized Ec-Trx. These missing amides
      correspond to residues Cys35-Glu39 in the active-site-containing helix (alpha2)
      and Ser72-Ile75 in a loop near the active site, and suggest a change in backbone
      dynamics on the millisecond-to-microsecond timescale associated with the breakage
      of an intramolecular Cys32-Cys35 disulfide bond in a thioredoxin. A consequence
      of the missing amide resonances is the absence of observable or unambiguous NOEs
      to provide the distance restraints necessary to define the N-terminal end of the
      alpha-helix containing the CPGC active site in the reduced state. This region
      adopts a well defined alpha-helical structure in other reported reduced
      thioredoxin structures, is mostly helical in oxidized Ec-Trx and CD studies of Ec
      Trx in both redox states suggests there is no significant difference in the
      secondary structure of the protein. The NMR solution structure of reduced Ec-Trx
      illustrates that the absence of canonical structure in a region of a protein may
      be owing to unfavorable dynamics prohibiting NOE observations or unambiguous NOE
      assignments.

PMID- 29372908
TI  - Crystal structures of the archaeal RNase P protein Rpp38 in complex with RNA
      fragments containing a K-turn motif.
AB  - A characteristic feature of archaeal ribonuclease P (RNase P) RNAs is that they
      have extended helices P12.1 and P12.2 containing kink-turn (K-turn) motifs to
      which the archaeal RNase P protein Rpp38, a homologue of the human RNase P
      protein Rpp38, specifically binds. PhoRpp38 from the hyperthermophilic archaeon
      Pyrococcus horikoshii is involved in the elevation of the optimum temperature of
      the reconstituted RNase P by binding the K-turns in P12.1 and P12.2. Previously,
      the crystal structure of PhoRpp38 in complex with the K-turn in P12.2 was
      determined at 3.4 A resolution. In this study, the crystal structure of PhoRpp38
      in complex with the K-turn in P12.2 was improved to 2.1 A resolution and the
      structure of PhoRpp38 in complex with the K-turn in P12.1 was also determined at
      a resolution of 3.1 A. Both structures revealed that Lys35, Asn38 and Glu39 in
      PhoRpp38 interact with characteristic G.A and A.G pairs in the K-turn, while
      Thr37, Asp59, Lys84, Glu94, Ala96 and Ala98 in PhoRpp38 interact with the three
      nucleotide bulge in the K-turn. Moreover, an extended stem-loop containing P10
      P12.2 in complex with PhoRpp38, as well as PhoRpp21 and PhoRpp29, which are the
      archaeal homologues of the human proteins Rpp21 and Rpp29, respectively, was
      affinity-purified and crystallized. The crystals thus grown diffracted to a
      resolution of 6.35 A. Structure determination of the crystals will demonstrate
      the previously proposed secondary structure of stem-loops including helices P12.1
      and P12.2 and will also provide insight into the structural organization of the
      specificity domain in P. horikoshii RNase P RNA.

PMID- 29372911
TI  - Prognostic Impact of Pretreatment Fluorodeoxyglucose Positron Emission
      Tomography/Computed Tomography SUVmax in Patients With Locally Advanced Cervical
      Cancer.
AB  - OBJECTIVE: The aim of this study was to investigate the impact of SUVmax
      fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)
      measured in the primary tumor, pelvic and para-aortic node with disease-free
      survival (DFS) and overall survival (OS) in patients with locally advanced
      cervical cancer. METHODS AND MATERIALS: A total of 92 patients with histological
      diagnosis of locally advanced cervical cancer are treated with radiochemotherapy
      plus brachytherapy boost from January 2008 to April 2014 in our Institution. A
      pretreatment FDG-PET/CT for staging and radiotherapy planning was performed, and
      the value of SUVmax measured in primary tumor and positive nodes was related to
      DFS and OS. RESULTS: Univariate analysis showed that DFS is related to FDG-PET/CT
      positive para-aortic nodes (P = 0.01), International Federation of Gynecology and
      Obstetrics (FIGO) stage of disease (P = 0.01), and primary tumor SUVmax (P =
      0.02), and OS is related to positive para-aortic nodes (P = 0.01) and primary
      tumor SUVmax (P = 0.02).In multivariate analysis, DFS is modified by FDG-PET/CT
      positive para-aortic lymph nodes, stage and high T SUVmax (P = 0.02; P = 0.003; P
      = 0.04), but the only worse prognostic factor of OS is the high SUVmax in the
      primary tumor (P = 0.01). CONCLUSIONS: We found that T SUVmax, stage, and para
      aortic lymph node status assessed by FDG-PET were independent prognostic factors
      of DFS, whereas only T SUVmax correlated with OS.

PMID- 29372909
TI  - Structure of the mouse acidic amino acid decarboxylase GADL1.
AB  - Pyridoxal 5'-phosphate (PLP) is a ubiquitous cofactor in various enzyme classes,
      including PLP-dependent decarboxylases. A recently discovered member of this
      class is glutamic acid decarboxylase-like protein 1 (GADL1), which lacks the
      activity to decarboxylate glutamate to gamma-aminobutyrate, despite its homology
      to glutamic acid decarboxylase. Among the acidic amino acid decarboxylases, GADL1
      is most similar to cysteine sulfinic acid decarboxylase (CSAD), but the
      physiological function of GADL1 is unclear, although its expression pattern and
      activity suggest a role in neurotransmitter and neuroprotectant metabolism. The
      crystal structure of mouse GADL1 is described, together with a solution model
      based on small-angle X-ray scattering data. While the overall fold and the
      conformation of the bound PLP are similar to those in other PLP-dependent
      decarboxylases, GADL1 adopts a more loose conformation in solution, which might
      have functional relevance in ligand binding and catalysis. The structural data
      raise new questions about the compactness, flexibility and conformational
      dynamics of PLP-dependent decarboxylases, including GADL1.

PMID- 29372913
TI  - Eu(iii) and Cm(iii) tetracarbonates - in the quest for the limiting species in
      solution.
AB  - The structural and spectroscopic properties of the compounds
      [C(NH2)3]5[Gd:M(CO3)4(H2O)].0.75H2O (1) and [C(NH2)3]5[Y:M(CO3)4].2H2O (2) (M =
      Eu, Cm) were determined. The crystals contain differently hydrated tetracarbonate
      complexes, [M(CO3)4(H2O)]5- and [M(CO3)4]5-, which were used as structural and
      spectroscopic models of Eu(iii) and Cm(iii) tetracarbonate species in aqueous
      solutions. The luminescence spectra of the crystals were used to establish the
      stoichiometry and stability of the limiting species of the aqueous Eu(iii) and
      Cm(iii) carbonate systems at different temperatures and in a broad range of ionic
      strengths. By implementing this method together with the Pitzer approach used for
      the description of highly concentrated systems, it was possible to determine the
      thermodynamic functions of the reaction [Eu(CO3)3]3- + CO32- ? [Eu(CO3)4]5- under
      standard conditions for the first time (DeltaH degrees  = 31.4 +/- 2 kJ mol-1 and
      DeltaS degrees  = 82 +/- 10 J mol-1 K-1). The proposed model for Eu(iii)
      carbonates is consistent with the data recorded for the Cm(iii)-carbonate
      systems. The presented results are important not only from the point of view of
      environmental issues, but also for the coordination chemistry of f-elements in
      general.

PMID- 29372912
TI  - [Assessment of worklife areas and stress intensity among Border Guard officers].
AB  - BACKGROUND: Stress is associated with the performance of high-risk occupations.
      It can be defined as a set of reactions that results from mismatched working
      conditions and requirements to capabilities of an employee. People who
      differently assess these areas of work may experience varying degrees of stress.
      MATERIAL AND METHODS: The total of 128 Border Guard officers took part in the
      test. A subjective assessment of areas of work was made by using the Areas of
      Worklife Survey. The Perceived Stress Scale (PSS-10) was used to examine the
      severity of stress. RESULTS: Three groups of examined people, differing
      significantly in the assessment of all areas of working life, were identified.
      Affiliation of the examined people to these groups explains 8% of the variability
      in the severity of stress. The results of the regression analysis allowed to
      consider the assessments of 3 areas of working life (control, rewards and
      workload) as important predicators of the severity of stress experienced by
      officers. The model turned out to be statistically significant, the variables
      included in the model explain 19% of the variability of the dependent variable.
      CONCLUSIONS: The officers who assess the areas of working life differently,
      differ in terms of severity of the experienced stress. The severity of stress is
      significantly related to the ability to make independent decisions and to enjoy
      rewards. The stress experienced by Border Guard officers is mainly related to the
      assessment of the following areas of work: sense of control, rewards and
      workload. Med Pr 2018;69(2):199-210.

PMID- 29372914
TI  - Could new U(ii) complexes be accessible via tuning hybrid heterocalix[4]arene? A
      theoretical study of redox and structural properties.
AB  - Tuning the building blocks of pyrrole and arene/pyridine in hybrid
      heterocalix[4]arene allows for the possible accessibility of several intriguing
      divalent uranium complexes, which are energetically stabilized by enhanced
      delta(U-Ar) bonds and further corroborated by computed UIII/II reduction
      potentials.

PMID- 29372915
TI  - Removal of the Fe(iii) site promotes activation of the human cystic fibrosis
      transmembrane conductance regulator by high-affinity Zn(ii) binding.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel
      is activated by ATP binding at the interface of two cytoplasmic nucleotide
      binding domains (NBDs) and phosphorylation of the regulatory (R) domain by
      protein kinase A (PKA). The human CFTR has two functionally active thiol groups
      for gating regulation by chemical modification. Although modification of C832 in
      the R domain with N-ethylmaleimide promotes channel opening, glutathionylation of
      C1344 in NBD2 inhibits channel opening. Our recent studies demonstrated that the
      N-ethylmaleimide-induced potentiation involves a high-affinity inhibitory Fe3+
      site at the interface between the R domain and intracellular loop 3 (ICL3).
      However, it is unknown whether the glutathionylation-evoked inhibition implies
      another stimulatory metal site. Here, Fe3+-insensitive mutations at the R-ICL3
      interface were employed to further examine whether Zn2+ potentiated the activity
      of the human CFTR channel by targeting C1344 once the interfacial Fe3+ bridge was
      disrupted. The results showed that internal nanomolar Zn2+ increased its activity
      by about two- to threefold at a low level of protein kinase A, and the increase
      was reversed by EDTA or DTT or reduced glutathione but suppressed by a high level
      of protein kinase A, N-ethylmaleimide modification or a C1344A mutation. It is
      interesting that this Zn2+-triggered potentiation is not found in the wild type
      human CFTR to which endogenous Fe3+ is bound. Thus, the high-affinity binding of
      Zn2+ to C1344 in NBD2 may stimulate human CFTR activity in a phosphorylation
      dependent manner, but the primary binding of Fe3+ to the ICL3-R interface may
      prohibit this stimulation.

PMID- 29372916
TI  - Network structure of SnO2 hollow sphere/PANI nanocomposites for electrochemical
      performance.
AB  - Homogeneous SnO2 hollow spheres have been synthesized through a hydrothermal
      method without a template, followed by in situ polymerization of PANI. The
      resulting SnO2 hollow spheres were uniformly deposited onto the surface or
      embedded into the PANI nanofibers to form a SnO2-PANI network structure. As
      electrode materials, the SnO2-PANI composites exhibit greatly enhanced specific
      capacitance (477 F g-1 at a current density of 1 A g-1) and superior cycling
      performance (no capacitance loss after 3000 galvanostatic charge-discharge
      cycles). These intriguing features are attributed to the interaction between the
      SnO2 hollow spheres and PANI network. On the one hand, the SnO2 spheres not only
      provide larger area for electrochemical reaction but also release volume
      expansion during the charge-discharge process. On the other hand, the conducting
      PANI improves electrical conductivity and maintains mechanical integrity of the
      composites as well.

PMID- 29372917
TI  - The synergistic effect of Ceria and Co in N-doped leaf-like carbon nanosheets
      derived from a 2D MOF and their enhanced performance in the oxygen reduction
      reaction.
AB  - Novel two-dimensional Ceria@Co, N-doped leaf-like porous carbon nanosheets (Ce
      HPCNs) were fabricated using an efficient aqueous solution-mediated method. More
      importantly, the prepared Ce-HPCNs demonstrate even better electrocatalytic
      performance than the commercial Pt/C due to the synergistic effect of the oxygen
      buffer CeO2 with Co-Nx, and exhibit a new direction and impact in the development
      of new catalysts for energy applications.

PMID- 29372918
TI  - Iron-catalyzed C(sp3)-H functionalization of N,N-dimethylanilines with
      isocyanides.
AB  - An efficient ligand-free Fe-catalyzed oxidative Ugi-type reaction toward the
      assembly of alpha-amino amides and short peptides is described. The reaction
      proceeds through the alpha-C(sp3)-H oxidation of N,N-dimethylanilines and further
      nucleophilic attack of the resulting iminium species by isocyanides. Additive
      screening showed that judicious choice of the carboxylic acid could lead to the
      formation of alpha-amino imides via a 3-component reaction. The process occurs
      with operational simplicity and is compatible with a variety of sensitive
      functional groups.

PMID- 29372919
TI  - Electrochemical surface-enhanced Raman spectroscopy (EC-SERS) study of the
      interaction between protein aggregates and biomimetic membranes.
AB  - Human diseases characterized by the uncontrolled deposition of insoluble
      extracellular protein aggregates are collectively referred to as amyloidoses.
      Such diseases include Alzheimer's, Parkinson's, Huntington's, and prion disease.
      In Alzheimer's disease, it is believed that amyloid-beta proteins may be
      responsible for pore and defect formation within cellular membranes, leading to a
      breakdown of cellular homeostasis causing eventual neuronal death. This theory is
      referred to as the amyloid pore hypothesis of Alzheimer's disease. In this work,
      the interaction between a model amyloid-forming protein (insulin) and a
      biomimetic membrane was studied at the molecular level. Protein at different
      stages of aggregation was allowed to interact with a biomimetic membrane formed
      on a nanostructured substrate using Langmuir-Blodgett/Langmuir-Schaefer
      deposition. Electrochemical surface-enhanced Raman spectroscopy (EC-SERS) was
      used to monitor the molecular level changes occurring as a result of this
      interaction. Based on the results it was observed that oligomers and protofibrils
      caused the most significant membrane deterioration whilst native protein appeared
      to play a protective role. To the best of our knowledge, this work represents the
      first EC-SERS investigation of protein aggregate-biomembrane interactions, and
      highlights the usefulness of this tool for studying complex biomolecular
      interactions.

PMID- 29372920
TI  - Proton and oxygen ion conductivity in the pyrochlore/fluorite family of Ln2
      xCaxScMO7-delta (Ln = La, Sm, Ho, Yb; M = Nb, Ta; x = 0, 0.05, 0.1) niobates and
      tantalates.
AB  - The tolerance factor is a good criterion to understand the structural transitions
      in Ln2-xCaxScMO7-delta (Ln = La, Sm, Ho, Yb; M = Nb, Ta; x = 0, 0.05, 0.1).
      Decreasing the Ln ionic radius in Ln2ScNb(Ta)O7 leads to a morphotropic
      transition from a pyrochlore to a fluorite-like structure. Ca2+-doping leads to a
      pyrochlore-to-fluorite transition in Ln2-xCaxScMO7-delta (Ln = La, Sm) and a
      fluorite-to-pyrochlore transition in Ho2-xCaxScNbO7-delta. Proton contribution to
      the total conductivity was observed for Ln2-xCaxScNb(Ta)O7-delta (Ln = La, Sm; x
      = 0, 0.05, 0.1) 3+/5+ pyrochlores and the maximum proton contribution was shown
      by Sm1.9Ca0.1ScMO6.95 (M = Nb, Ta), which are located at the boundary between
      pyrochlores and fluorites (comparative study of electrical conduction and oxygen
      diffusion). Proton conduction of Sm1.9Ca0.1ScNbO6.95 and Sm1.9Ca0.1ScTaO6.95
      pyrochlores persists up to 800 and 850  degrees C, respectively. The conductivity
      of fluorite-like Ho2-xCaxScNbO7-delta (x = 0, 0.05) and Yb2ScNbO7 is dominated by
      the oxygen ion transport, in accordance with their energy activation values 1.09
      1.19 eV. The dielectric permittivity and TG studies were used for the
      investigation of oxygen vacancy dynamics and water incorporation into the Ln2
      xCaxScNb(Ta)O7-delta (Ln = La, Sm, Ho, Yb; x = 0, 0.05, 0.1) lattice. It is shown
      that oxygen vacancy-related dielectric relaxation in the range of 550-650 
      degrees C (ambient air), typical of pyrochlores and fluorites with pure oxygen
      ion conductivity, decreases and disappears for proton-conducting oxides.

PMID- 29372921
TI  - Evolutionary selection of personalized melanoma cell/tissue dual-homing peptides
      for guiding bionanofibers to malignant tumors.
AB  - Both melanoma cells and tissues were allowed to interact with an identical pool
      of billions of human-safe phage nanofiber clones with each genetically displaying
      a unique 12-mer peptide at the tips, respectively, resulting in the discovery of
      bionanofibers displaying a melanoma cell/tissue dual-homing peptide for
      personalized targeted melanoma therapy.

PMID- 29372927
TI  - Pyrosome consumption by benthic organisms during blooms in the northeast Pacific
      and Gulf of Mexico.

PMID- 29372928
TI  - Albuminuria and Cerebral Small Vessel Disease: A Systematic Review and Meta
      Analysis.
AB  - OBJECTIVES: To determine whether albuminuria, a marker of systemic endothelial
      dysfunction, is associated with cerebral small vessel disease (SVD). DESIGN:
      Systematic review following the Meta-analyses Of Observational Studies in
      Epidemiology guidelines; independent reviewers searched Pubmed/Medline and
      Scopus, data were extracted, studies were evaluated on quality, and random
      effects models were implemented for meta-analysis. SETTING: Observational studies
      quantifying an association between albuminuria and cerebral SVD. PARTICIPANTS:
      Adults. MEASUREMENTS: Magnetic resonance imaging-defined markers of cerebral SVD;
      white matter hyperintensities (WMHs), lacunar infarcts (LIs), cerebral
      microbleeds (CMBs), and enlarged perivascular spaces (EPVSs). RESULTS: Of 31
      eligible studies comprising 23,056 participants identified, 27 were included in
      quantitative synthesis. Most of the studies were cross-sectional and of varying
      quality. On meta-analysis, albuminuria was associated with greater risk of WMHs
      (odds ratio (OR) = 1.70, 95% confidence interval (CI) = 1.43-2.01; 13,548
      subjects, 2,665 cases; I2  = 44%), LIs (OR = 1.86, 95% CI = 1.49-2.31; 12,857
      subjects, 998 cases; I2  = 27%), CMBs (OR = 1.78, 95% CI = 1.30-2.43; 7,645
      subjects; 748 cases; I2  = 39%), and EPVSs in the basal ganglia (OR = 1.78, 95%
      CI = 1.02-3.09; 1,388 subjects, 399 cases; I2  = 37%) and centrum semiovale (OR =
      3.27, 95% CI = 1.49-7.20; 1,146 subjects, 460 cases; I2  = 66%). Sensitivity
      analyses for high-quality and general population studies, but also studies
      controlling for cardiovascular disease risk factors and renal function, confirmed
      the findings and resolved the moderate heterogeneity and publication bias that
      were evident in the overall analyses. CONCLUSION: Albuminuria is independently
      associated with cerebral SVD, indicating shared microvascular pathology in the
      kidney and the brain. The results suggest that peripheral systemic microvascular
      disease biomarkers could be useful in the evaluation of brain microvascular
      damage.

PMID- 29372931
TI  - Spotlights are papers selected by editors published in peer-reviewed journals
      that may be more regionally specific or appearing in languages other than
      English.

PMID- 29372929
TI  - Gamma-glutamyl transferase predicts future stroke: A Korean nationwide study.
AB  - OBJECTIVE: Although gamma-glutamyl transferase (GGT) is generally regarded as an
      alternative biomarker for alcohol consumption, its independent role in vascular
      diseases emerged recently. However, its role in stroke remains unknown. The aim
      of this study is to clarify the impact of GGT on stroke in a large-sized,
      national, standardized population cohort in Korea. METHODS: In Korea, the
      National Health Insurance Service (NHIS) provides full-coverage health insurance
      service for all citizens. Using data from the NHIS, the NHIS-National Sample
      Cohort was designed by randomly selecting 2% of Koreans, carefully considering
      demographic characteristics. We analyzed eligible individuals from this
      standardized cohort. The Cox proportional hazards model was used for the study
      investigating the relationship between GGT and stroke. RESULTS: Among the 456,100
      eligible participants, 7,459 patients (1.64%) developed stroke as follows: 5,789
      ischemic strokes, 1,046 intracerebral hemorrhages (ICHs), and 624 subarachnoid
      hemorrhages. GGT was independently correlated with increased risk of stroke after
      adjustment for alcohol consumption and stroke risk factors (hazard ratio [HR] =
      1.39, 95% confidence interval [CI] = 1.29-1.51). The risks of both ischemic
      stroke (HR = 1.45, 95% CI = 1.32-1.58) and ICH (HR = 1.46, 95% CI = 1.18-1.80)
      were significantly elevated with increasing GGT. Despite some effect
      modifications by sex, age, and alcohol, the risk of total stroke and ischemic
      stroke in association with GGT remained significant in all subgroups.
      INTERPRETATION: In a standard Korean population, GGT was a novel biomarker
      predicting stroke risk, independently from alcohol consumption and other risk
      factors. Ann Neurol 2018;83:375-386.

PMID- 29372930
TI  - Eliciting adverse effects data from participants in clinical trials.
AB  - BACKGROUND: Analysis of drug safety in clinical trials involves assessing adverse
      events (AEs) individually or by aggregate statistical synthesis to provide
      evidence of likely adverse drug reactions (ADR). While some AEs may be
      ascertained from physical examinations or tests, there is great reliance on
      reports from participants to detect subjective symptoms, where he/she is often
      the only source of information. There is no consensus on how these reports should
      be elicited, although it is known that questioning methods influence the extent
      and nature of data detected. This leaves room for measurement error and
      undermines comparisons between studies and pooled analyses. This review
      investigated comparisons of methods used in trials to elicit participant-reported
      AEs. This should contribute to knowledge about the methodological challenges and
      possible solutions for achieving better, or more consistent, AE ascertainment in
      trials. OBJECTIVES: To systematically review the research that has compared
      methods used within clinical drug trials (or methods that would be specific for
      such trials) to elicit information about AEs defined in the protocol or in the
      planning for the trial. SEARCH METHODS: Databases (searched to March 2015 unless
      indicated otherwise) included: Embase; MEDLINE; MEDLINE in Process and Other Non
      Indexed Citations; Cochrane Methodology Register (July 2012); Cochrane Central
      Register of Controlled Trials (February 2015); Cochrane Database of Systematic
      Reviews; Database of Abstracts of Reviews of Effects (January 2015); Health
      Technology Assessment database (January 2015); CINAHL; CAB Abstracts; BIOSIS
      (July 2013); Science Citation Index; Social Science Citation Index; Conference
      Proceedings Citation Index - Science. The search used thesaurus headings and
      synonyms for the following concepts: (A): Adverse events AND measurement; (B):
      Participants AND elicitation (also other synonyms for extraction of information
      about adverse effects from people); (C): Participants AND checklists (also other
      synonyms as for B). Pragmatic ways were used to limit the results whilst trying
      to maintain sensitivity. There were no date or sample size restrictions but only
      reports published in English were included fully, because of resource constraints
      as regards translation. SELECTION CRITERIA: Two types of studies were included:
      drug trials comparing two or more methods within- or between-participants to
      elicit participant-reported AEs, and research studies performed outside the
      context of a trial to compare methods which could be used in trials (evidenced by
      reference to such applicability). Primary outcome data included AEs elicited from
      participants taking part in any such clinical trial. We included any participant
      reported data relevant for an assessment of drug-related harm, using the original
      authors' terminology (and definition, where available), with comment on whether
      the data were likely to be treatment-emergent AEs or not. DATA COLLECTION AND
      ANALYSIS: Titles and abstracts were independently reviewed for eligibility. Full
      texts of potentially eligible citations were independently reviewed for final
      eligibility. Relevant data were extracted and subjected to a 100% check.
      Disagreements were resolved by discussion, involving a third author. The risk of
      bias was independently assessed by two authors. The Cochrane 'Risk of bias' tool
      was used for reports comparing outcomes between participants, while for within
      participant comparisons, each study was critically evaluated in terms of
      potential impact of the design and conduct on findings using the framework of
      selection, performance, detection, attrition, reporting, and other biases. An
      attempt was made to contact authors to retrieve protocols or specific relevant
      missing information. Reports were not excluded on the basis of quality unless
      data for outcomes were impossible to compare (e.g. where denominators differed).
      A narrative synthesis was conducted because differences in study design and
      presentation meant that a quantitative meta-analysis was not possible. MAIN
      RESULTS: The 33 eligible studies largely compared open questions with checklist
      type questions or rating scales. Two included participant interviews. Despite
      different designs, populations and details of questioning methods, the narrative
      review showed that more specific questioning of participants led to more AEs
      detected compared to a more general enquiry. A subset of six studies suggested
      that more severe, bothersome, or otherwise clinically relevant AEs were reported
      when an initial open enquiry was used, while some less severe, bothersome, or
      clinically relevant AEs were only reported with a subsequent specific enquiry.
      However, two studies showed that quite severe or debilitating AEs were only
      detected by an interview, while other studies did not find a difference in the
      nature of AEs between elicitation methods. No conclusions could be made regarding
      the impact of question method on the ability to detect a statistically
      significant difference between study groups. There was no common statistical
      rubric, but we were able to represent some effect measures as a risk ratio of the
      proportion of participants with at least one AE. This showed a lower level of
      reporting for open questions (O) compared to checklists (CL), with a range for
      the risk ratios of 0.12 to 0.64. AUTHORS' CONCLUSIONS: This review supports
      concerns that methods to elicit participant-reported AEs influence the detection
      of these data. There was a risk for under-detection of AEs in studies using a
      more general elicitation method compared to those using a comprehensive method.
      These AEs may be important from a clinical perspective or for patients. This
      under-detection could compromise ability to pool AE data. However, the impact on
      the nature of the AE detected by different methods is unclear. The wide variety
      and low quality of methods to compare elicitation strategies limited this review.
      Future studies would be improved by using and reporting clear definitions and
      terminology for AEs (and other important variables), frequency and time period
      over which they were ascertained, how they were graded, assessed for a
      relationship to the study drug, coded, and tabulated/reported. While the many
      potential AE endpoints in a trial may preclude the development of general AE
      patient-reported outcome measurement instruments, much could also be learnt from
      how these employ both quantitative and qualitative methods to better understand
      data elicited. Any chosen questioning method needs to be feasible for use by both
      staff and participants.

PMID- 29372933
TI  - Targeting apoptosis pathways in infections.
AB  - The programmed cell death pathway of apoptosis is essential for mammalian
      development and immunity as it eliminates unwanted and dangerous cells. As part
      of the cellular immune response, apoptosis removes the replicative niche of
      intracellular pathogens and enables the resolution of infections. To subvert
      apoptosis, pathogens have evolved a diverse range of mechanisms. In some
      circumstances, however, pathogens express effector molecules that induce
      apoptotic cell death. In this review, we focus on selected host-pathogen
      interactions that affect apoptotic pathways. We discuss how pathogens control the
      fate of host cells and how this determines the outcome of infections. Finally,
      small molecule inhibitors that activate apoptosis in cancer cells can also induce
      apoptotic cell death of infected cells. This suggests that targeting host death
      factors to kill infected cells is a potential therapeutic option to treat
      infectious diseases.

PMID- 29372934
TI  - Clinical outcome of Descemet's stripping endothelial keratoplasty with
      femtosecond laser-prepared grafts.

PMID- 29372936
TI  - 2018: The dog year ahead.

PMID- 29372937
TI  - Editorial to the Special Issue "Stem Cell Characterization Across Species".

PMID- 29372938
TI  - Second-Generation Antipsychotic-Induced Hypoglycemia.
AB  - Complaints of hypoglycemia resemble the sedative effect of antipsychotics. As
      such, clinicians may overlook hypoglycemia in patients with psychiatric
      disorders. Here, a case of hypoglycemia associated with hyperinsulinemia induced
      by quetiapine in a female patient with bipolar disorder is reported. The case
      suggests that clinicians should be aware of the potential for hypoglycemia
      induced by second-generation antipsychotics.

PMID- 29372939
TI  - Can Statins Diminish Depression?
AB  - Depression is a common malady associated with numerous chronic medical conditions
      such as coronary artery disease, hypertension, and diabetes. Statins provide
      protection against coronary and cerebrovascular diseases by decreasing
      cholesterol synthesis in the liver. Statin medications also reduce inflammation.
      Since the pathophysiology of depression involves inflammation, statins could have
      a role in the treatment of mood disorders and might become a pharmacotherapy
      option for patients experiencing depression. There is evidence suggesting an
      antidepressant effect when statins are adjunctively co-prescribed with
      antidepressant medicines. However, confounding data also exist refuting a
      positive effect of these drugs at elevating mood. More research is required to
      confirm a potentially beneficial effect of prescribing statins to people with
      clinical depression.

PMID- 29372941
TI  - Patient Reported Outcomes.

PMID- 29372940
TI  - Delusional Psychosis in Graves' Disease.

PMID- 29372942
TI  - Preventing Excessive Gestational Weight Gain and Postpartum Weight Retention.

PMID- 29372943
TI  - Investigating the Barriers to the Uptake of Diabetic RetinaScreen.
AB  - Diabetic retinopathy is a significant complication of diabetes, and the most
      common cause of blindness in people under the age of 65. The National Diabetic
      Retinal Screening Programme (Diabetic RetinaScreen) was established to detect
      sight threatening retinopathies. The purpose of this cross-sectional study is to
      determine the barriers to the uptake of Diabetic RetinaScreen, to investigate
      discrepancies in attendance, if any, between patients whose diabetes care is
      delivered in a large tertiary referral hospital out-patient setting or in general
      practice, and to evaluate general practitioner&apos;s satisfaction with the
      service. Older age (OR 1.023, 95% CI 1.001 to 1.046) and complications of
      diabetes, excluding ocular complications, (OR 2.741, 95% CI 1.158 to 6.489) were
      associated with increased attendance at Diabetic RetinaScreen. Online referral is
      now available and the preferred method of referral. Efforts to encourage younger
      patients who do not yet have complications of diabetes may be beneficial.

PMID- 29372944
TI  - Determination of the Lung Clearance Index (LCI) in a Paediatric Cystic Fibrosis
      Cohort.
AB  - The pathogenesis of CF lung disease may start in infancy. Therefore, it is
      important to monitor the early stages of its progress. The Exhalyzer D is the
      first commercially available device designed to measure lung ventilation
      inhomogeneity at any age. This study was conducted to assess the performance and
      feasibility of using the Exhalyzer D in a paediatric CF clinic. A total of 91
      subjects were recruited (23 controls, and 68 patients with CF). The majority of
      CF patients (79%) and controls (78%) completed at least two successful washouts.
      A strong linear correlation was noted between LCI and FEV1. Children with CF
      under six years of age struggled to perform the washout in a technically correct
      manner. A clear learning effect was observed, with improved technique and shorter
      testing times on repeated visits.

PMID- 29372945
TI  - Decrease in the Uptake of Seasonal Influenza Vaccine in Persons Aged 65 Years and
      Older In Ireland since the 2009 Influenza A (H1N1) Pdm09 Pandemic.
AB  - In Ireland, there is year-on-year variation in the seasonal influenza vaccine
      uptake for people aged 65 years and older. We obtained aggregate vaccine uptake
      data (2004/05-2014/15) by area and age group and applied the 2011 relative
      deprivation score and GP-density by area. Using Poisson regression model, we
      estimated the associations between those variables and uptake before and after
      the 2009 pandemic. After adjusting for age, deprivation status and GP-density,
      overall persons aged ?65 years were less likely to receive the vaccine after the
      pandemic compared to before (RR=0.89, 95%CI: 0.82-0.96). Uptake increased with
      age; both those in the 70-74 and ?75 year age groups were more likely to receive
      the vaccine compared to those aged 65-69 years (RR=1.18, 95%CI:1.14-1.24;
      RR=1.34, 95%CI:1.28-1.39 respectively). Qualitative studies should be undertaken
      to explore whether changes in public perception on risks of the disease and the
      vaccine and/or public funding and policy influenced the uptake.

PMID- 29372946
TI  - Self-Harm, Methadone Use and Drug-Related Deaths amongst Those Registered As
      Being of No Fixed Abode or Homeless in Ireland.
AB  - This work aims to contribute to the evidence base regarding the health of those
      who experience homelessness in Ireland by collating data on methadone use, drug
      related deaths and emergency department presentations due to self-harm. Data from
      the Central Methadone Treatment List (CTL), National Self-Harm Registry Ireland
      and the National Drug-Related Deaths Index were analysed. The percentage on the
      CTL registered as being of no fixed abode (NFA) or homeless increased from 2% to
      7% from 2011-2014. The absolute number of presentations with deliberate self-harm
      from those of NFA increased by 49% from 2007-2014. The number of drug-related
      deaths amongst those of NFA or homeless and who died in Dublin fluctuated from
      2004-13 with an overall upward trend. There is an urgent need to adequately
      resource and coordinate those services which aim to address factors (social and
      health inequalities, mental ill-health and addiction) which lead people into -
      and prevent them exiting from - homelessness.

PMID- 29372947
TI  - The Perception of Art among Patients and Staff on a Renal Dialysis Unit.
AB  - This study investigated the purpose and effectiveness of giving outpatients an
      opportunity to engage in art activities while receiving dialysis treatment. A
      mixed method study was conducted. 21 semi-structured interviews were conducted
      with outpatients attending the dialysis unit and 13 surveys of clinicians were
      completed. The principle reasons to partake in the art activity programme
      included: to pass time, to relieve boredom, to be creative, to try something new,
      distraction from concerns, to stay positive and to achieve something new.
      Patients who did not participate in the programme pass their time primarily by
      watching TV or sleeping. All staff who partook in the survey were satisfied with
      the programme and wanted it to continue. Our findings indicate that the creative
      arts programme is viewed positively by staff and patients alike, and might be
      useful in other hospital departments. Further in depth qualitative research would
      be useful to interrogate the potential effect of engagement in art on positive
      mental health and quality of life for patients with chronic conditions.

PMID- 29372948
TI  - Menorrhagia Outcomes of Minimally Invasive Treatments (MOMITS): A 2 to 5-year
      follow-up.
AB  - We conducted a retrospective postal questionnaire-based study to assess the
      effectiveness and patient experience of minimally invasive treatments for
      menorrhagia by performing a two- to five-year follow up of patient symptoms.
      Questionnaires were distributed to 111 and 117 women following thermal balloon
      endometrial ablation (TBEA) and levonorgestrel intrauterine system (LNG-IUS),
      with response rates of 58.5% and 43.6% respectively. Sanitary pad use during the
      heaviest day of bleeding reduced by 8.4 and 5.2 pads in the TBEA and LNG-IUS
      groups respectively (p<0.05). An improvement in patients' quality of life (QOL)
      score exceeding 10 points was found in 79% and 61% in the TBEA and LNG-IUS groups
      respectively. Patient satisfaction (PS) improved in all areas, more so regarding
      participation in social activities in the TBEA group (p<0.05). Women undergoing
      TBEA would recommend the procedure to other women in 95%, and 93% in the LNG-IUS
      group. TBEA and LNG-IUS are highly acceptable management options for the
      treatment of menorrhagia, with improvement in QOL, PS and menstrual blood loss.

PMID- 29372949
TI  - Antenatal Pertussis Vaccination: Why are General Practitioners Reluctant? A Mixed
      Methods StudySetting.
AB  - Pertussis has a disproportionately higher morbidity and mortality in infants less
      than 3 months of age. International and national guidelines recommend pertussis
      vaccination during pregnancy, as a safe and effective way to protect these
      infants. Antenatal pertussis vaccination uptake rates remain suboptimal, with
      many health care professionals (HCPs) still not recommending it. The reasons
      underlying this reluctance on behalf of HCPs have not been fully established.
      This study aims to evaluate the current practice and attitudes of General
      Practitioners (GPs) with regard to antenatal pertussis vaccination. An embedded
      mixed method design was used. The response rate was 41% (n=109). 54% of GPs who
      responded (n=59) routinely recommend antenatal pertussis vaccination. Safety
      concerns and a sense of isolation emerged as the major qualitative themes. More
      safety data, adequate funding from the Health Service Executive (HSE) and support
      from secondary care may help to increase the GP recommendation rate and enhance
      vaccination uptake in pregnancy.

PMID- 29372950
TI  - Surgical Site Infection after Caesarean Section? There Is an App for That:
      Results from a Feasibility Study On Costs and Benefits.
AB  - Surgical site infections (SSIs) are one of the most common and, yet, preventable
      healthcare associated infections. In Ireland, the rate of Caesarean section (CS)
      is increasing, while postpartum hospital stay is decreasing, adversely affecting
      SSI among women. There is much need to develop post-discharge surveillance which
      can effectively monitor, detect, and arrange treatment for affected women. The
      use of modern technology to survey SSI following discharge from hospital remains
      unexplored. We report the results of a feasibility study which investigates
      whether an integrated mobile application (hereafter, app) is more cost-beneficial
      than a stand-alone app or telephone helpline at surveying SSI following CS. We
      find women prefer the integrated app (47.5%; n=116/244) over the stand-alone app
      (8.2%; n=20/244) and telephone helpline (18.0%; 44/244), although there is no
      significant difference in women's valuation of these services using willingness
      to pay techniques. The stand-alone app is the only cost-beneficial service due to
      low labour costs. Future research should employ alternative measures when
      evaluating the benefits of the health technology. The use of a mobile app as a
      mechanism for postpartum care could represent a considerable advancement towards
      technological health care.

PMID- 29372951
TI  - Interaction of Broadband Access and Education Levels in Determining the Rate of
      Emergency Medical Admissions.
AB  - Background We examined the effect of broadband access, educational status and
      their interaction on local population health. Methods We calculated the annual
      admission incidence rates for each small area population unit within our hospital
      catchment, relating quintiles of broadband access to two groups a) full time
      education to primary level (less than or equal to 15 years) and b) full time
      education to tertiary level (>18 years). Univariate and multivariable risk
      estimates were calculated, using truncated Poisson regression. Results 82,368
      admissions in 44,628 patients were included. Broadband access was a linear
      predictor of the admission incidence rate with decreases from Q1 (least access)
      50.8 (95%CI 30.2 to 71.4) to Q5 (highest access) 17.9 (95%CI 13.4 to 22.4). Areas
      with greater numbers educated only to primary level were more influenced by
      broadband access. Conclusion Broadband access is a predictor of the emergency
      medical admission rate; this effect is modulated by the baseline education level.

PMID- 29372952
TI  - Acute Respiratory Failure Post Single Lung Transplantation: An Unusual Cause.
AB  - Vascular complications of pulmonary vessels post-transplant are rare but are
      associated with high morbidity and mortality. We describe the first published
      case of surgical management of pulmonary vein stenosis complicated by early
      thrombosis post single lung transplantation. This report describes early
      diagnostic techniques and subsequent management options in such patients where
      pulmonary vascular complications are a potential.

PMID- 29372953
TI  - An Unusual Presentation of Sarcoidosis.
AB  - Bilateral pleural effusions are a rare manifestation of sarcoidosis. We describe
      here the case of a 30 year old Vietnamese man living in Ireland who presented
      with a 4 month history of cough, dyspnoea on exertion and fatigue. On chest CT,
      he was found to have bilateral pleural effusions, bihilar lymphadenopathy and
      multiple pulmonary nodules. Pleural biopsy confirmed the presence of non
      caseating granulomas. He was commenced on steroids with excellent clinical
      response.

PMID- 29372954
TI  - Treatment Options for Amelobastic Carcinoma of the Mandible: A Case Series and
      Review of the Literature.
AB  - We retrospectively review the only three cases in the Irish National
      Maxillofacial Unit over a 12-year period. Methods involved retrospectively
      reviewing clinical notes, radiology and histopathology of three cases. Case one
      was an 80-year-old male presenting with mandibular swelling, who received
      radiotherapy alone. Case two was a 26-year-old male with swelling and
      odynophagia. He underwent left hemimandibulectomy and fibular free flap
      reconstruction. Case three was a 64-year-old female with mental nerve involvement
      who underwent a right hemimandibulectomy. The cases presented here illustrate a
      diverse sample regarding patient demographics and management approaches. Surgery
      usually necessitates en bloc resection, free flap reconstruction and 1-1.5 cm
      margins. Adjuvant radiotherapy may be required for close margins.

PMID- 29372955
TI  - Donegal Going against the Flow: National Differences in Long-Term Urinary
      Catheterisation Rates in Men (> 65 Years) With Benign Prostatic Hypertrophy.
AB  - An analysis of Primary Care Reimbursement Service (PCRS, 2013) data demonstrated
      high rates of urinary catheter changes in Donegal compared to other regions of
      Ireland. There is a catheter change rate of 10.2% in Donegal men over 65 with
      medical cards (GMS) compared to rates of 2.7% and 0.17% in Waterford and South
      Dublin, respectively1. This 60-fold difference between an area with perceived
      good access to services (South Dublin) and Donegal an area that does not,
      prompted a survey of general practitioners in each of these areas to assess
      whether true male catheterisation rates were similarly disproportionate in
      Donegal. Based on this, data was collected from a population of 23,794 GMS
      patients in GP training practices in Donegal (Rural), Leinster (Urban) and
      Waterford (Suburban). The data sampled for Donegal demonstrated 19 long-term
      catheters (LTCs per 8603 GMS) compared to four LTCs (per 5,800 GMS) in Leinster
      and 3 LTCs (per 9,391 GMS) in Waterford (Table 1). This anomaly in LTC rates may
      be a proxy for lack of access to basic Urology services.

PMID- 29372956
TI  - Prevalence and Seasonal Variation of Incidental MRI Paranasal Inflammatory
      Changes in an Asymptomatic Irish Population.
AB  - Inflammatory changes in the paranasal sinuses are a common incidental finding on
      magnetic resonance imaging (MRI) of the head and neck. This study aimed to assess
      the prevalence and seasonal variation of inflammatory paranasal sinus changes in
      an asymptomatic Irish population. Retrospective analysis was performed on 221
      patients who underwent brain MRI at the time points of winter and summer. T2
      weighted sequences were evaluated for paranasal sinus disease. Nearly half the
      patients in the study exhibited morphological paranasal sinus changes on imaging
      suggesting that these could be considered a normal variant. Correlation of
      imaging findings with clinical symptoms and signs remain crucial to the diagnosis
      of sinusitis.

PMID- 29372958
TI  - Judge Obstetricians by Intention; Not Intervention.

PMID- 29372959
TI  - A Case of Pleuroparenchymal Fibroelastosis.

PMID- 29372957
TI  - Bisphosphonates in General Practice: An Audit on the Management of Osteoporosis.

PMID- 29372960
TI  - [Control of the gene activity by polycomb and trithorax group proteins in
      Drosophila].
AB  - Combinatorial expression of the genes in multicellular organisms leads to the
      development of different cell types. The important epigenetic regulators of
      higher eukaryotes are the Polycomb group (PcG) and Trithorax group (TrxG)
      proteins. These factors control the transcription of a large number of genes
      involved in various cellular processes. Dysregulation of PcG and TrxG systems
      leads to developmental abnormalities and cancer. This review focuses on the main
      characteristics and properties of the Drosophila PRE elements. Furthermore, we
      summarize the information on the protein components of the PcG and TrxG groups
      and their functional activities and discuss the main aspects of competition
      between the proteins of these classes as well as their possible mechanisms of
      action.

PMID- 29372961
TI  - [Coactivator complexes participate in different stages of the Drosophila
      melanogaster hsp70 gene transcription].
AB  - The objective of this study was to identify transcriptional coactivators
      participating in transcription elongation of the hsp70 gene induced by heat
      shock. We found that all investigated coactivator complexes participate in
      transcription of this gene, as significant level of them were present at the gene
      promoter in its active state. For most of the coactivators (except for p300/CBP,
      Set2, and Mediator complex), we also observed a considerable increase of their
      binding level at the coding region of the gene after activation of its
      transcription by heat shock. We assume that coactivators CHD1, ISWI, Brm, Kismet
      L, INO80, Mi-2, Gcn5, Lid/KDM5, Set1, DART1, DART4, SSRP1, PAF1, and Fs(1)h/Brd4
      bind to the promoter of the active hsp70 gene and migrate to its coding region
      together with elongating RNA polymerase II. It can be suggested that some of
      these coactivators play an important role in stimulating the transition of the
      RNA polymerase II complex from transcription initiation to elongation stage.

PMID- 29372963
TI  - [Histone-like protein H-NS as a negative regulator of quorum sensing systems in
      gram-negative bacteria].
AB  - The effects of histone-like protein H-NS on transcription of promoters of the
      Quorum Sensing regulated operons from marine luminescent mesophilic bacterium
      Aliivibrio fischeri and psychrophilic Aliivibrio logei, as well as from
      pathogenic Pseudomonas aeruginosa, are studied. In the present work, the plasmids
      carrying DNA fragments with the promoters Pr1f (upstream of the luxICDABEG operon
      from A. fischeri), Pr1l (upstream of the luxCDABEG operon from A. logei), Pr2l
      (upstream of luxI gene from A. logei), PluxCf (upstream of luxC gene from A.
      fischeri), and PlasI (upstream of lasI gene from P. aerugenosa) are used. In
      these plasmids, promoter-operator regions are transcriptionally fused to the
      reporter genes cassette luxCDABE from Photorhabdus luminescens. Here we have
      shown that the transcription of the QS-regulated promoters in E. coli hns::kan
      cells increases 100 to 1000 times. Furthermore, transcription of the QS-regulated
      promoters in E. coli hns + cells increases 10 to 100 times in the cells
      transformed with the plasmid carrying gene ardA ColIb-P9 encoding DNA mimic
      antirestriction protein ArdA, inhibitor of the type I restriction-modification
      systems.

PMID- 29372964
TI  - [The role of remodeling complexes CHD1 and ISWI in spontaneous and UV-induced
      mutagenesis control in yeast Saccharomyces cerevisiae].
AB  - Chromatin remodulators are special multiprotein machines capable of transforming
      the structure, constitution, and positioning of nucleosomes on DNA. Biochemical
      activities of remodeling complexes CHD1 and ISWI from the SWI2/SNF2 family are
      well established. They ensure correct positioning of nucleosomes along the
      genome, which is probably critical for genome stability, in particular, after
      action of polymerases, repair enzymes, and transcription. In this paper, we show
      that single mutations in genes ISW1, ISW2, and CHD1 weakly affect repair and
      mutagenic processes in yeast cells. At the same time, there are differences in
      the effect of these mutations on spontaneous mutation levels, which indicates
      certain specificity of action of protein complexes ISW1, ISW2, and CHD1 on
      expression of different genes that control repair and mutation processes in
      yeast.

PMID- 29372965
TI  - [Polymorphic sites in transcribed spacers of 35S rRNA genes as an indicator of
      origin of the Paeonia cultivars].
AB  - Region ITS1-5.8S rDNA-ITS2 is sequenced in 27 varieties of cultivated ornamental
      peonies, ten of which presumably originate from Paeonia lactiflora, one from P.
      officinalis, 13 from hybridization of P. lactiflora and P. peregrina, or P.
      officinalis, and three are Itoh hybrids. Comparative analysis of distribution
      patterns of polymorphic sites (PS) for the obtained DNA sequences and data from
      GenBank is carried out. Hypotheses of origin of the studied varieties, except for
      two, which, as previously assumed, originate from hybridization of P. lactiflora
      and P. peregrina, are confirmed. It is shown that the sequence ITS1-5.8S rDNA
      ITS2 is a good genetic marker for cultivars of the P. lactiflora group and Itoh
      hybrids, and that the PS distribution patterns in these sequences can provide
      valuable information on the kinship and origin of individual varieties. However,
      insufficient knowledge of wild species from the P. officinalis kinship group
      limits the use of this marker in the study of varieties obtained through
      interspecific hybridization within the Paeonia section.

PMID- 29372966
TI  - [Analysis of microsatellite loci variability in rare and endemic species Allium
      regelianum A.K. Becker ex Iljin].
AB  - SSR analysis of rare and endemic species Allium regelianum, which grows in the
      south of Russia, was performed for the first time. Variability analysis of 88
      accessions of A. regelianum was carried out using four highly polymorphic
      microsatellite loci (PIC value ranged from 0.55 to 0.72). SSR-analysis made it
      possible to revealed polymorphism within and among the populations of A.
      regelianum from Volgograd region. Analysis of Wright's F-statistics and the
      analysis of molecular variance showed that more than 90% of total genetic
      variation of the species was attributed to the differences within the populations
      and less than 10% of the differences were found among the populations. Cluster
      analysis of 46 accessions of A. regelianum from three populations of Volgograd
      region and principal coordinate analysis of all accessions did not reveal
      differentiation among the populations.

PMID- 29372967
TI  - [Fish growth hormone genes: Divergence of coding sequences in salmonid fishes].
AB  - Comparison of coding nucleotide sequences of the paralogous GH1 and GH2 genes, as
      well as of the growth hormone amino acid sequences, in the species of closely
      related salmonid genera Salvelinus, Oncorhynchus, and Salmo was performed. It was
      demonstrated that, in different groups of salmonids, the amino acid substitution
      rates were considerably different. In some cases, an obvious discrepancy between
      the divergence of growth hormone genes and phylogenetic schemes based on other
      methods and approaches was revealed. These findings suggest that the reason may
      be multidirectional selection at duplicated genes at different stages of
      evolution.

PMID- 29372968
TI  - Gold Nanoparticles Compromise TNF-alpha-Induced Endothelial Cell Adhesion
      Molecule Expression Through NF-kappaB and Protein Degradation Pathways and Reduce
      Neointima Formation in A Rat Carotid Balloon Injury Model.
AB  - The aim of this study was to investigate the anti-inflammatory effects and
      mechanism of action of the gold nanoparticles (AuNPs) on vascular injury. In
      vitro vascular endothelial cell (EC) inflammation and in vivo rat carotid balloon
      injury models were used. The expression of TNF-alpha-induced cell adhesion
      molecules (CAMs) was suppressed by the AuNPs in human umbilical vein ECs and
      aortic ECs. The AuNPs reduced TNF-alpha-induced intracellular ROS production and
      NF-kappaB signaling pathways and enhanced CAM protein degradation by increasing
      their ubiquitination. However, they did not interfere with the mTOR pathway for
      protein synthesis and TNF-alphabinding to ECs. These effects led to a reduction
      of monocyte adhesion to EC monolayers in vitro and endothelial CAM expression and
      monocyte/macrophage level in the vascular injured areas, contributing to a
      substantial decrease of arterial neointima formation in the rat carotid balloon
      injury model. The serum gold concentration was 99.5+/-18 ng/ml after three-day
      oral administration. Moreover, incubation of the AuNPs with serum and albumin led
      to an increase of particle sizes of the AuNPs. Collectively, we provide the first
      evidence that demonstrates that AuNPs possess anti-inflammatory bioactivity on
      vascular ECsin vitro and can reduce arterial neointima hyperplasia during
      vascular injury in vivo.

PMID- 29372969
TI  - [The genetic diversity of burbot (Lota lota L., 1758) of Western Siberia (the
      analysis of the mtDNA control region polymorphism)].
AB  - The genetic variability of burbot (Lota lota L., 1758) inhabiting the Ob-Irtysh
      and Taz river basins in Western Siberia has been studied based on the
      polymorphism of the hypervariable fragment of mtDNA control region (407 bp). The
      analysis of 134 fish samples revealed 30 haplotypes, 23 of which were new. Among
      haplotypes, previously detected in Eurasia and North America, EB30 was the most
      frequently found in Western Siberia (45.5% frequency). The results of our study
      are in agreement with previous research pointing to the genetic differentiation
      of two burbot subspecies, L. l. lota and L. l. maculosa, and indicate that burbot
      inhabiting the Ob-Irtysh and Taz river basins belong to the Eurasian-Beringian
      clade (nominative subspecies L. l. lota). However, a high genetic diversity of
      burbot in Western Siberia, along with a relatively high differentiation of burbot
      groups within studied territory, points to a regional specificity of burbot
      population.

PMID- 29372970
TI  - [Genetic diversity of the Pacific walrus (Odobenus rosmarus divergens) in the
      western part of the Chukchi Sea].
AB  - We study 117 Pacific walrus samples from three rookeries within the western part
      of Chukchi Sea (Cape Vankarem, Cape Serdtse-Kamen, and Kolyuchin Island). We
      analyze the variability of nuclear (20 microsatellite loci) and mitochondrial DNA
      (three fragments). Two microsatellite loci which are described as microsatellites
      for the first time are used in this study: repeated sequences within introns of
      Coro1c and Plod2 genes. A high degree of genetic diversity is demonstrated for
      both nuclear and mitochondrial markers compared to Atlantic walrus. A high degree
      of genetic diversity is preserved within populations of Pacific walrus, despite a
      strong decline in the recent past. We discover the absence of significant
      differentiation for microsatellite loci and the presence of weak differentiation
      for mtDNA (mainly for a D-loop fragment). Walrus specimens that use the rookeries
      of the western part of Chukchi Sea are thought to belong to a single reproductive
      group.

PMID- 29372971
TI  - Multifunctional Surface-Enhanced Raman Spectroscopy-Detectable Silver
      Nanoparticles Combined Photodynamic Therapy and pH-Triggered Chemotherapy.
AB  - This research paper reports the development of a multifunctional anti-cancer
      prodrug system based on silver nanoparticles. This prodrug system is composed of
      70-nm sized nanoparticles and features photodynamic therapeutic properties and
      active, pH-triggered drug release. The silver nanoparticles are decorated with a
      folic acid (FA) targeting ligand via an amide bond, and also conjugated to the
      chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond.
      Both FA and DOX are attached to the silver nanoparticles through a polyethylene
      glycol (PEG) spacer. This prodrug system can preferentially enter cells that over
      express folic acid receptors, with subsequent intracellular drug release
      triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier
      system exhibits photodynamic therapeutic (PDT) activity, so that the cell
      viability of cancer cells that overexpress folate receptors can be further
      reduced upon light irradiation. The dual effects of pH-triggered drug release and
      PDT increase the therapeutic efficacy of this system. The multifunctional
      nanoparticles can be probed intracellularly through Surface-Enhanced Raman
      Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores
      the applicability of this multifunctional silver nanoparticle-based system for
      cancer theranostics.

PMID- 29372972
TI  - [Molecular phylogenetic analysis of Diacyclops and Acanthocyclops (Copepoda:
      Cyclopoida) from Lake Baikal].
AB  - Lake Baikal is inhabited by a relatively large number of cyclopid species, many
      of which are endemics. Two genera, Diacyclops Kiefer, 1927 and Acanthocyclops
      Kiefer, 1927, are the most specious in the lake. Taxonomic discrimination of the
      majority of representatives of these genera is difficult owing to their high
      morphological similarities and poor standard description. In this study, a
      molecular phylogenetic analysis of Lake Baikal members of the
      Diacyclops/Acanthocyclops group is performed on the basis of mitochondrial
      cytochrome c oxidase subunit I (COI) gene. It is shown that a fragment of COI
      1000 bp long is sufficient for intragenus discrimination of the cyclopids of Lake
      Baikal. The issues of Diacyclops/Acanthocyclops taxonomy are reflected in the
      obtained molecular data. Two distinct phylogenetic groups of Diacyclops genus
      with uncertain taxonomic status are revealed.

PMID- 29372973
TI  - [Assessment of the genetic distances between some species of the family
      Bradybaenidae (Mollusca, Pulmonata)].
AB  - On the basis of inter-simple sequence repeat (ISSR) loci and the nucleotide
      sequences of nuclear (18S and ITS-1) and mitochondrial genes (COI and 16S), a
      phylogenetic analysis of the three species of terrestrial mollusks of the family
      Bradybaenidae (Mollusca, Pulmonata), Bradybaena fruticum Mull., Bradybaena
      schrencki Midd., and Bradybaena transbaicalia Shileyko, was conducted to clarify
      their taxonomic status. The analysis showed that Br. fruticum was far apart from
      the other two species (Br. schrencki and Br. transbaicalia). The genetic distance
      between the latter puts in doubt their status as distinct species. It is
      suggested that the species Br. transbaicalia can be treated as a form of Br.
      schrencki var. transbaicalia.

PMID- 29372974
TI  - [Developing forensic reference database by 18 autosomal STR for DNA
      identification in Republic of Belarus].
AB  - For the Republic of Belarus, development of a forensic reference database on the
      basis of 18 autosomal microsatellites (STR) using a population dataset (N =
      1040), "familial" genotypic dataset (N = 2550) obtained from expertise
      performance of paternity testing, and a dataset of genotypes from a criminal
      registration database (N = 8756) is described. Population samples studied consist
      of 80% ethnic Belarusians and 20% individuals of other nationality or of mixed
      origin (by questionnaire data). Genotypes of 12346 inhabitants of the Republic of
      Belarus from 118 regional samples studied by 18 autosomal microsatellites are
      included in the sample: 16 tetranucleotide STR (D2S1338, TPOX, D3S1358, CSF1PO,
      D5S818, D8S1179, D7S820, THO1, vWA, D13S317, D16S539, D18S51, D19S433, D21S11,
      F13B, and FGA) and two pentanucleotide STR (Penta D and Penta E). The samples
      studied are in Hardy-Weinberg equilibrium according to distribution of genotypes
      by 18 STR. Significant differences were not detected between discrete populations
      or between samples from various historical ethnographic regions of the Republic
      of Belarus (Western and Eastern Polesie, Podneprovye, Ponemanye, Poozerye, and
      Center), which indicates the absence of prominent genetic differentiation.
      Statistically significant differences between the studied genotypic datasets also
      were not detected, which made it possible to combine the datasets and consider
      the total sample as a unified forensic reference database for 18 "criminalistic"
      STR loci. Differences between reference database of the Republic of Belarus and
      Russians and Ukrainians by the distribution of the range of autosomal STR also
      were not detected, corresponding to a close genetic relationship of the three
      Eastern Slavic nations mediated by common origin and intense mutual migrations.
      Significant differences by separate STR loci between the reference database of
      Republic of Belarus and populations of Southern and Western Slavs were observed.
      The necessity of using original reference database for support of forensic
      expertise practice in the Republic of Belarus was demonstrated.

PMID- 29372975
TI  - Intranasal Administration of chitosan-Coated Nanostructured Lipid Carriers Loaded
      with GDNF Improves Behavioral and Histological Recovery in a Partial Lesion Model
      of Parkinson's Disease.
AB  - Parkinson's disease (PD) is the second most frequent neurodegenerative disorder,
      but current therapies are only symptomatic. A promising alternative to address
      the neurodegenerative process is the use of neurotrophic factors, such as the
      glial cell-derived neurotrophic factor (GDNF). However, its clinical use has been
      limited due to its short half-life and rapid degradation after in vivo
      administration, in addition to difficulties in crossing the blood-brain barrier
      (BBB). This barrier is a limiting factor in brain drug development, making the
      future progression of neurotherapeutics difficult. In the past few years,
      intranasal drug delivery has appeared as an alternative non-invasive
      administration route to bypass the BBB and target drugs directly to the CNS.
      Thus, the aim of this work was to study the in vivo neuroprotective effect of
      intranasally administered GDNF, encapsulated in chitosan-coated nanostructured
      lipid carrier (CS-NLC-GDNF), in a 6-OHDA partially lesioned rat model. The
      developed CS-NLC-GDNF showed a particle size of approximately 130 nm and high
      encapsulation efficiency. The in vitro study in PC-12 cells demonstrated the
      ability of the encapsulated GDNF to protect these cells against 6-OHDA toxin.
      After two weeks of daily intranasal administration of treatments, the
      administration of CS-NLC-GDNF achieved a behavioral improvement in rats, as well
      as a significant improvement in both the density of TH+ fibres in the striatum
      and the TH+ neuronal density in the SN. Thus, it can be concluded that the nose
      to-brain delivery of CS-NLC-GDNF could be a promising therapy for the treatment
      of PD.

PMID- 29372976
TI  - Rivaroxaban in Stable Cardiovascular Disease.

PMID- 29372977
TI  - Rivaroxaban in Stable Cardiovascular Disease.

PMID- 29372978
TI  - Rivaroxaban in Stable Cardiovascular Disease.

PMID- 29372979
TI  - Rivaroxaban in Stable Cardiovascular Disease.

PMID- 29372980
TI  - Rivaroxaban in Stable Cardiovascular Disease.

PMID- 29372981
TI  - Removal of Certain Time of Inspection and Duties of Inspector Regulations for
      Biological Products. Direct final rule.
AB  - The Food and Drug Administration (FDA, Agency, or we) is amending the general
      biologics regulations relating to time of inspection requirements and also
      removing duties of inspector requirements. FDA is taking this action to remove
      outdated requirements and accommodate new approaches, such as a risk-based
      inspection frequency for drug establishments, thereby providing flexibility
      without diminishing public health protections. This action is part of FDA's
      implementation of Executive Orders (E.O.s) 13771 and 13777. Under these E.O.s,
      FDA is comprehensively reviewing existing regulations to identify opportunities
      for repeal, replacement, or modification that will result in meaningful burden
      reduction while allowing the Agency to achieve our public health mission and
      fulfill statutory obligations. The Agency is issuing these amendments directly as
      a final rule because we believe they are noncontroversial and FDA anticipates no
      significant adverse comments.

PMID- 29372982
TI  - Applications of Quantum Dots in Cancer Detection and Diagnosis: A Review.
AB  - The mechanisms of carcinogenesis, cancer invasion and metastasis remain unclear
      because of the complexity of cancer cells and tumor microenvironment. Thus, the
      urgent development of a novel approach for cancer detection and real-time
      monitoring is crucial in order to decipher the intricate molecular information
      responsible for tumor biological behaviors. Quantum dots (QDs) are engineered
      fluorescent nanoparticles with unique optical and chemical properties, which have
      shown a great potential as promising platforms for biomedical applications. Here,
      we focus on the clinical applications of quantum dot-based nanotechnology in
      cancer detection and diagnosis, covering topics on individual cancer diagnosis
      and treatment by in-vitro and in-vivo molecular imaging technologies, sentinel
      lymph node (SLN) mapping, cancer associated proteins detection in blood,
      circulation tumor cells (CTCs) detection, and in-depth understanding of the
      biological behaviors from the perspective of tumor microenvironment. In addition,
      the major challenges in translating quantum dot-based detection methodologies
      into clinical applications and promising future directions are also discussed.

PMID- 29372983
TI  - The Cellular and Molecular Mechanisms Underlying Silver Nanoparticle/Chitosan
      Oligosaccharide/Poly(vinyl alcohol) Nanofiber-Mediated Wound Healing.
AB  - Wound healing is a complex pathophysiological process that occurs frequently in
      everyday pathology and remains a challenge during the treatment of trauma.
      Previously, we prepared silver nanoparticle/chitosan oligosaccharide/poly(vinyl
      alcohol) (PVA/COS-AgNP) nanofibers via an electrospinning technique. These
      nanofibers promoted the proliferation of human skin fibroblasts (HSFs) and the
      expression of transforming growth factor TGF-beta1 in the early stage of wound
      repair, although the specific mechanisms remain unclear. Therefore, considering
      that TGF-beta1 has emerged as a major modulator of wound healing, the objective
      of this study was to further understand whether the molecular mechanisms
      responsible for PVA/COS-AgNP nanofiber-mediated wound healing include the TGF
      beta1/Smad signal transduction pathway. In this study, we used human skin
      fibroblasts (HSFs) to investigate the molecular and cellular mechanisms
      underlying PVA/COSAgNP nanofiber-mediated wound healing. Cell adhesion and
      proliferation experiments, immunofluorescence staining, hydroxyproline content
      measurements, flow cytometry, quantitative real-time PCR (qRT-PCR), and western
      blotting (WB) were used to analyze the wound healing mechanisms of human skin
      fibroblasts treated with various concentrations of PVA/COS-AgNP nanofibers and
      the combined application of silver nanofibers and SB431542 (an inhibitor of the
      TGF-beta1 receptor kinase). Our study showed that PVA/COS-AgNP nanofibers
      markedly promoted fibroblast proliferation, collagen synthesis, and cell
      adherence. We also found that treating fibroblasts with PVA/COS-AgNP nanofibers
      stimulated cell cycle progression from G1 into the S and G2 phases, reducing the
      proportion of cells in the G0/G1 phase and inducing S and G2/M arrest.
      Importantly, the cell factors associated with the TGF-beta1/Smad signal
      transduction pathway, such as TGF-beta1, TGFbetaRI, TGFbetaRII, pSmad2, pSmad3,
      collagen I, collagen III, and fibronectin were also up-regulated. Moreover, this
      enhancing effect was markedly inhibited by the TGFbetaRI receptor inhibitor,
      SB431542. Therefore, the PVA/COS-AgNP nanofibers used to accelerate wound healing
      do so by activating the TGF-beta1/Smad signal transduction pathway.

PMID- 29372984
TI  - Surgery for Drug-Resistant Epilepsy in Children.

PMID- 29372985
TI  - Surgery for Drug-Resistant Epilepsy in Children.

PMID- 29372986
TI  - Characterization of DNA Condensation by Conformationally Restricted Dipeptides
      and Gene Delivery.
AB  - A wide variety of non-viral vectors have been developed for gene delivery in past
      few decades but find limited applications mainly due to lower encapsulation,
      endosomal entrapment, high toxicity and low transfection efficiency. In this
      work, we explored plasmid DNA binding ability of several low molecular weight
      dipeptides containing alpha,beta-dehydrophenylalanine (DeltaF) and found that an
      arginine containing dipeptide, arginine-alpha,beta-dehydrophenylalanine (R
      DeltaF) condensed pEGFP-N1 plasmid into positively charged spherical
      nanoparticles of size 250-275 nm. Single molecule techniques showed that R-DeltaF
      interacted with the plasmid DNA in a dose dependent manner which was accompanied
      by a decrease in diffusion time of the plasmid DNA as well as release of the
      bound fluorophore. The plasmid DNA in R-DeltaF-plasmid complex (R-DeltaF-Pl) was
      stable against DNase action. A pH dependent release of the plasmid DNA from R
      DeltaF-Pl was observed and the released plasmid DNA retained its natural
      conformation at endosomal pH, as evidenced from time correlated single photon
      counting. R-DeltaF-Pl was biocompatible and showed ready uptake in HEK 293T
      cells. Transfection assays using reporter plasmids for green fluorescent protein
      (GFP), luciferase enzyme and chloramphenicol acetyltransferase (CAT) showed R
      DeltaF mediated gene delivery both in the presence and absence of serum in the
      medium. Ease of synthesis, homogenous assembly and biocompatibility balanced with
      significant expression of gene of interest make R-DeltaF a potential vector for
      development for in vivo application.

PMID- 29372987
TI  - Fertility Preservation in Women.

PMID- 29372988
TI  - Measurement of In Vitro Single Cell Temperature by Novel Thermocouple Nanoprobe
      in Acute Lung Injury Models.
AB  - Energy metabolism may alter pattern differences in acute lung injury (ALI) as one
      of the causes but the detailed features at single-cellular level remain unclear.
      Changes in intercellular temperature and adenosine triphosphate (ATP)
      concentration within the single cell may help to understand the role of energy
      metabolism in causing ALI. ALI in vitro models were established by treating mice
      lung epithelial (MLE-12) cells with lipopolysaccharide (LPS), hydrogen peroxide
      (H2O2), hydrochloric acid (HCl) and cobalt chloride (CoCl2, respectively. 100 nm
      micro thermocouple probe (TMP) was inserted into the cytosol by micromanipulation
      system and thermoelectric readings were recorded to calculate the intracellular
      temperature based on standard curve. The total ATP contents for the MLE-12 cells
      were evaluated at different time intervals after treatments. A significant
      increase of intracellular temperature was observed after 10 or 20 MUg/L LPS and
      HCl treatments. The HCl increased the temperature in a dose-dependent manner. On
      the contrary, H2O2 induced a significant decline of intracellular temperature
      after treatment. No significant difference in intracellular temperature was
      observed after CoCl2 exposure. The intracellular ATP levels decreased in a time
      dependent manner after treatment with H2O2 and HCl, while the LPS and CoCl2 had
      no significant effect on ATP levels. The intracellular temperature responses
      varied in different ALI models. The concentration of ATP in the MLE-12 cells
      played part in the intracellular temperature changes. No direct correlation was
      observed between the intracellular temperature and concentration of ATP in the
      MLE-12 cells.

PMID- 29372989
TI  - Fertility Preservation in Women.

PMID- 29372990
TI  - Synthesis of One-Dimensional Pillar Arrays by Electrohydrodynamic Jet Printing
      for Glucose Sensor.
AB  - One-dimensional (1-D) Ag arrays were formed by electrohydrodynamic jet-printing
      (EHD) of polyvinylpyrrolidone (PVP, 1,300 k, Aldrich) solution ink. The 1-D Ag
      arrays were formed on slide glass by controlling the viscosity and printing
      conditions such as the tip to the substrate distance, the applied voltage, the
      flow rate of ink and the velocity. The printed pillars were dried at 80  degrees
      C to get rid of the solvent and sintered at 400  degrees C for 30 min. We found
      that the arrays of Ag pillars can be fabricated by using the EHD printing method.
      We could control the diameter of the pillars in the range of 100-200 MUm and the
      length rage between 300 and 700 MUm. In order to produce a better performance of
      glucose sensor, we infiltrated a glucose oxidase as a glucose detector into the
      Ag pillars previously coated with the mixed solution of multi-walled carbon
      nanotube (MWCNT, Iljin), Nafion and Pt nanoparticles. In addition, the Ag array
      electrode with glucose oxidase was used as a working electrode for glucose
      detection via the three-electrode electrochemical method.

PMID- 29372991
TI  - Evidence-based management of irritable bowel syndrome with diarrhea.
AB  - Irritable bowel syndrome (IBS), a complex disorder of the gastrointestinal tract,
      is characterized by abdominal pain associated with defecation or changes in stool
      form or frequency. IBS is associated with substantial burden, including direct
      medical costs and indirect costs. Direct costs associated with IBS in the United
      States have been estimated to exceed $1 billion. However, indirect costs, such as
      negative effect on quality of life (QOL) and work productivity, are difficult to
      quantify. There are 3 main subtypes: IBS with prominent diarrhea (IBS-D), IBS
      with constipation, and IBS with mixed symptoms of both constipation and diarrhea.
      A number of pharmacologic agents have been used to treat IBS-D despite lack of
      approval by the FDA for this indication. The pharmacologic agents that are
      indicated by the FDA for the treatment of IBS-D include alosetron, eluxadoline,
      and rifaximin. The negative impact of IBS-D symptoms on QOL reported by patients
      indicate there is an unmet need for therapies that effectively treat and manage
      the symptoms of this condition. Addressing gaps in treatment is an important
      priority.

PMID- 29372992
TI  - Telehealth

PMID- 29372993
TI  - Anti-hMC2RL1 Functionalized Gold Nanoparticles for Adrenocortical Tumor Cells
      Targeting and Imaging.
AB  - The low rate of cure of adrenocortical carcinomas (ACC) in children and adults is
      related to germ line TP53 mutation, late diagnosis, incomplete surgical
      resection, and lack of an efficient adjunctive therapy. To provide a new approach
      for the improvement of ACC diagnosis and therapy, the present study aimed to
      explicitly target ACC cells using gold nanoparticle (AuNP) probes bound to
      specific antibodies. Immunohistochemistry of ACC and positive and negative
      control tissue micro-sections under light microscopy was used to test a purified
      polyclonal antibody raised against the 80-93, outer loop 1 position of the human
      melanocortin receptor 2 (hMC2R). Both this and a control commercial antibody were
      found to specifically target cells known to express hMC2R. These were bound to
      FITC-labeled AuNPs and tested via direct immunofluorescence using the H295R ACC
      cell line. Both probes recognized only cells expressing hMC2R and exhibited very
      low background. Further studies are required to ascertain the potential of AuNPs
      bound to ACC cells for tumor diagnostics via imaging analysis or as a delivery
      device for targeted therapy.

PMID- 29372995
TI  - The Eminent Domain of Sanitary Science and the Usefulness of State Boards in
      Guarding the Public Welfare.

PMID- 29372996
TI  - Sugar-Sweetened Beverage Tax in West Virginia.

PMID- 29372997
TI  - Medical Marijuana Legal in West Virginia?

PMID- 29372998
TI  - The New Approach for Establishing the Cellular Response Guideline for Medical
      Applications of Polydiacetylene as Innovative Parameters.
AB  - Argon plasma jet (Ar-PJ) has been widely used in clinical medicine; however, the
      cellular effects of Ar-PJ therapy applying to living tissues have not been
      clarified yet. It is necessary to investigate cellular responses to Ar-PJ in
      establishing guidelines on the therapeutic use of Ar-PJ. Interestingly, in the Ar
      PJ-treated cells, the fragmented mitochondria, a typical cellular stress
      indicator, were discovered even in the cells located in the live zones (1~3
      zones). Using microscopic measurements of the mitochondrial length, we found that
      the fragmented mitochondria were mainly in the zones 1 and 2, the closest to the
      direct exposure point of Ar-PJ. Whereas, the mitochondria in the zone 4 retained
      their lengths to normal. This quantitative measurement of mitochondrial
      morphology was combined with the color scores of the polymerizable supramolecular
      (PS) sensor in diagnostic categories. The results demonstrate that the
      mitochondrial length (0.98~3.94 MUm) is inversely proportional to the PS sensor
      color scores (87~0) in the zones 1~4. On the combination of these three
      diagnostic parameters, the effective range of Ar-PJ for cellular responses was
      determined: the zones 1~3, the color scores 87~12 and the mitochondrial lengths
      0.98~2.57 MUm. Our study is the first demonstration of mitochondrial
      fragmentation in response to Ar-PJ and the first attempt to establish the
      diagnostic guideline for Ar-PJ therapies by combinations with biological,
      physical and chemical aspects. Thus, this study will make great advances in the
      field of bioplasma applications.

PMID- 29372999
TI  - Death Certificates: Cardiac Arrest is not a Cause of Death.

PMID- 29373002
TI  - Progressive Supranuclear Palsy - A Case Study from the Perspective of a Primary
      Care Physician Son.
AB  - Progressive Supranuclear Palsy (PSP) is a rare geriatric pathology, from the
      abnormal deposition of the tau protein, combining the motor tremor and
      bradykinesia of Parkinson's disease with the cognitive defects of Alzheimer's
      disease.  As physical and mental debilities progressively manifest in PSP, the
      physician, family, and patient face decisions on how to manage this terminal
      neurodegenerative disease.  Physicians note the outcomes of decisions and often
      express, either to peers or internally to oneself, how they would handle a
      similar situation affecting their own family.  In this case, we will explore PSP
      and examine a physician's perspective as his father navigates his journey through
      it.

PMID- 29373003
TI  - Curcumin Acetate Nanocrystals for sustained Pulmonary Delivery: Preparation,
      Characterization and In Vivo Evaluation.
AB  - The main objective of this study was to test the hypothesis that inhaled
      nanocrystals of a highly lipophilic drug could be used as a novel approach for
      producing sustained pulmonary delivery. Curcumin acetate, an ester prodrug of
      curcumin, was utilized as a highly lipophilic model drug. Curcumin acetate was
      subjected to wet ball milling to produce different particle sizes of nanocrystals
      and microparticles, and the milled curcumin acetate was spray-dried to yield
      similar inhalable microparticles. Following intrapulmonary administration in
      rats, pharmacokinetic experiments indicated that curcumin acetate significantly
      extended the pulmonary absorption time by 7.2-fold compared to curcumin, possibly
      due to the high lipophilicity of the former. The biodistribution data showed that
      aerosolized curcumin acetate nanocrystals 123.7 nm in size not only prolonged
      pulmonary retention, with the AUC value of curcumin acetate being 7.62-fold
      higher than that of the microparticles 1120 nm in size, but also increased the
      local in vivo release rate by 3.3-fold and the local availability of converted
      curcumin by 25.1-fold. In addition, the improved local availability resulted in
      better pharmacological efficacy in a monocrotaline-induced rat model of pulmonary
      arterial hypertension. This study was the first to demonstrate that inhalable
      nanocrystals are a feasible means for the sustained pulmonary delivery of highly
      lipophilic drugs.

PMID- 29373004
TI  - Acquires Anterior Thoracic Lung Herniation and Repair: A Rare Case and
      Discussion.
AB  - We report a case of acquired anterior thoracic lung herniation in a 63-yeal-old
      female.  This painful herniation developed four years after uncomplicated video
      assisted thoracic surgery for lung cancer resection and adjuvant radiation for
      concomitant breast cancer.  The herniation site was remote from all prior
      incisions, and demonstrated intercostal muscle denervation and radiation
      fibrosis.  The 8 cm x 10 cm chest wall defect was reconstructed with inlay
      PROCEED mesh and reinforced with a pedicled latissimus dorsi flap.  Five months
      postoperatively the patient had complete resolution of symptoms, no evidence of
      herniation, and a stable wound.

PMID- 29373005
TI  - Effect of Nanodiamond and Nanoplatinum Liquid, DPV576, on Human Primary
      Keratinocytes.
AB  - Nanofabrics are now being used in a wide range of products that come into direct
      contact with skin, including carpet, clothing, and medical fabrics. In the
      current study, we examined the effect of a dispersed aqueous mixture of
      nanodiamond (ND) and nanoplatinum (NP) (DPV576) on human primary keratinocytes
      with respect to transient receptor potential vanilloid (TRPV) channel expression,
      secretion of cytokines and production of nerve growth factor (NGF). Keratinocytes
      were treated with DPV576 at concentrations of 1:10 and 1:100 dilutions for 24
      hours in vitro, and their activation of was determined by production of cytokines
      TNF-alpha, IL-1beta, and prostaglandin (PGE2), and by production of NGF.
      Inhibitor experiments were carried out by incubating keratinocytes with the TRPV4
      selective antagonist HC-067047. TRPV receptor expression (TRPV1, TRPV3 and TRPV4)
      on keratinocytes as well as changes in Ca2+ potential were examined by flow
      cytometry. DPV576 treatment of keratinocytes resulted in the following effects:
      (1) stimulation of keratinocytes as indicated by the significant secretion of
      cytokines IL-1beta, TNF-alpha, and PGE2, an effect noted only at higher
      concentration (1:10); (2) significant decrease in the expression of TRPV4 on
      keratinocytes with a spike in the calcium flux, but no change in the expression
      of TRPV1 and TRPV3; (3) induction of cytokine secretion independent of TRPV4, as
      the addition of TRPV4 inhibitor had no significant effect on the cytokine
      production from keratinocytes; (4) induction of NGF secretion by keratinocytes.
      These results demonstrate that DPV576 activates keratinocytes via multiple
      signaling pathways which may reduce stress associated with inflammation, pain,
      and circadian rhythms. ND/NP-coated fabrics that target the modulation of local
      inflammation, pain, and circadian rhythms could potentially be of benefit to
      humans.

PMID- 29373006
TI  - The War on Drugs...or Doctors?

PMID- 29373007
TI  - New Schedule for Administering HPV Vaccinations.

PMID- 29373008
TI  - Inverse Opal-like Porous MoSex Films for Hydrogen Evolution Catalysis:
      Overpotential-Pore Size Dependence.
AB  - Transition metal dichalcogenides (TMDs) are prized as electrocatalysts for
      hydrogen evolution reaction (HER). Common TMD syntheses entail conditions of high
      temperatures and reagents that are detrimental to the environment. The
      electrochemical synthesis of TMDs is advocated as a viable alternative to the
      conventional synthetic procedures in terms of simplicity, ecological
      sustainability, and versatility of deposition on various surfaces at room
      temperature. In this work, we demonstrate the successful fabrication of
      electrocatalytic inverse opal porous MoSex films, where 2 <= x <= 3, via solid
      template-assisted electrodeposition from the simultaneous electroreduction of
      molybdic acid and selenium dioxide as the respective metal and chalcogen
      precursors in an aqueous electrolyte. The electrosynthesized porous MoSex films
      contain pores with diameters of 0.1, 0.3, 0.6, or 1.0 MUm, depending on the size
      of the polystyrene bead template used. The investigation reveals that porous
      MoSex films with a pore size of 0.1 MUm, which prevailed over the other pore
      sizes, are endowed with the lowest HER overpotential of 0.57 V at -30 mA cm-2 and
      a Tafel slope of 118 mV dec-1, alluding to the adsorption step as rate limiting.
      Across all pore sizes, the Volmer adsorption step limits the HER mechanism.
      Nevertheless, the pore size dictates the catalytic activity of the porous MoSex
      films apropos of HER overpotential such that the HER performance of smaller pore
      sizes of 0.1 and 0.3 MUm surpasses those with wider pore sizes of 0.6 and 1.0
      MUm. The observed trends in their HER behavior may be rationalized by the tunable
      surface wettability as pore sizes vary. These fundamental findings offer a
      glimpse into the efficacy of electrodeposited porous TMDs as electrocatalysts and
      exemplify the feasibility of the electrosynthesis method in altering the
      morphological structure of the TMDs.

PMID- 29373010
TI  - Copolymers of Bis-Diketopyrrolopyrrole and Benzothiadiazole Derivatives for High
      Performance Ambipolar Field-Effect Transistors on Flexible Substrates.
AB  - We develop an "acceptor dimerization" strategy by a bis-diketopyrrolopyrrole
      (2DPP) for an ambipolar organic semiconductor. Copolymers of 2DPP and
      benzothiadiazole (BTz) derivatives, P2DPP-BTz and P2DPP-2FBTz, are designed and
      synthesized. Both of the polymers exhibit narrow optical bandgaps of ca. 1.30 eV.
      The strong electron-withdrawing property of 2DPP results in low-lying lowest
      unoccupied molecular orbital (LUMO) energy levels of the polymers, improving the
      electron mobilities. 2D grazing incident X-ray diffraction and atomic force
      microscopy indicate that the P2DPP-BTz exhibits a small pi-pi stacking distance
      of 3.59 A and a smooth interface, thus promoting high mobility. To take full
      advantage of the flexibility of organic semiconductors, flexible field-effect
      transistors (FETs) were fabricated on poly(ethylene terephthalate) (PET)
      substrates. The FETs based on P2DPP-BTz show high performance with hole and
      electron mobilities of 1.73 and 2.58 cm2 V-1 s-1, respectively. Our results
      demonstrate that the 2DPP acceptor is a promising building block for high
      mobility ambipolar polymers.

PMID- 29373011
TI  - Oversampling To Improve Spatial Resolution for Liquid Extraction Mass
      Spectrometry Imaging.
AB  - Liquid extraction mass spectrometry imaging (MSI) experiments provide users with
      direct analysis of biological surfaces with minimal sample preparation. Until
      now, much of the effort to increase spatial resolution for MSI with liquid
      extraction techniques has focused on reducing the size of the sampling area.
      However, this can be experimentally challenging. Here, we present oversampling as
      a simple alternative to increase the spatial resolution using nanospray
      desorption electrospray ionization (nano-DESI) MSI. By imaging partial rat spinal
      cord tissue sections, two major concerns with oversampling are addressed: whether
      endogenous molecules are significantly depleted from repeated sampling events and
      whether analytes are redistributed as a result of oversampling. In depth
      examination of ion images for representative analytes show that depletion and
      redistribution do not affect analyte localization in the tissue sample. Nano-DESI
      MSI experiments using three times oversampling provided higher spatial
      resolution, allowing the observation of features not visible with undersampling.
      Although proper care must be taken to ensure that oversampling will work in
      specific applications, we envision oversampling as a simple approach to increase
      image quality for liquid extraction MSI techniques.

PMID- 29373012
TI  - Are the Risks from Microplastics Truly Trivial?

PMID- 29373009
TI  - Genome Mining and Assembly-Line Biosynthesis of the UCS1025A Pyrrolizidinone
      Family of Fungal Alkaloids.
AB  - UCS1025A is a fungal polyketide/alkaloid that displays strong inhibition of
      telomerase. The structures of UCS1025A and related natural products are featured
      by a tricyclic furopyrrolizidine connected to a trans-decalin fragment. We mined
      the genome of a thermophilic fungus and activated the ucs gene cluster to produce
      UCS1025A at a high titer. Genetic and biochemical analysis revealed a PKS-NRPS
      assembly line that activates 2S,3S-methylproline derived from l-isoleucine,
      followed by Knoevenagel condensation to construct the pyrrolizidine moiety.
      Oxidation of the 3S-methyl group to a carboxylate leads to an oxa-Michael
      cyclization and furnishes the furopyrrolizidine. Our work reveals a new strategy
      used by nature to construct heterocyclic alkaloid-like ring systems using
      assembly line logic.

PMID- 29373013
TI  - Efficient Access to Imidazo[1,2- a]pyridines/pyrazines/pyrimidines via Catalyst
      Free Annulation Reaction under Microwave Irradiation in Green Solvent.
AB  - An expeditious catalyst-free heteroannulation reaction for imidazo[1,2-
      a]pyridines/pyrimidines/pyrazines was developed in green solvent under microwave
      irradiation. Using H2O-IPA as the reaction medium, various substituted 2
      aminopyridines/pyrazines/pyrimidines underwent annulation reaction with alpha
      bromoketones under microwave irradiation to provide the corresponding imidazo[1,2
      a]pyridines/pyrimidines/pyrazines in excellent yields. The synthetic methodology
      appears to be very simple and superior to the already reported procedures with
      the high abundance of commercial reagents and great ability in expanding the
      molecular diversity. The present synthetic sequence is visualized as an
      environmentally benign process which allows the introduction of three points of
      structural diversity to expand chemical space with excellent purity and yields.
      The anti-inflammatory and antimicrobial activities of the derivatives were
      evaluated. Screening results uncovered three derivatives with strong inhibition
      of albumin denaturation and two derivatives were active on Proteus and Klebsiella
      bacteria. These positive bioassay results implied that the library of potential
      anti-inflammatory agents could be rapidly prepared in an ecofriendly manner, and
      provided new insights into drug discovery for medicinal chemists.

PMID- 29373014
TI  - Dual-Modal Probe Based on Polythiophene Derivative for Pre- and Intraoperative
      Mapping of Lymph Nodes by SPECT/Optical Imaging.
AB  - The metastatic spread of primary tumors to regional lymph nodes (LNs) is an
      important prognostic indicator for cancer staging and clinical therapy.
      Therefore, developing lymphatic mapping probes with improved accuracy and
      efficiency is of vital importance. Conjugated polymers (CPs) have been
      established as useful optical probes for sensitive biological and chemical
      detection. As a member of CPs family, polythiophene derivatives have drawn
      increasing attraction because of their superior photostability, signal
      amplification ability, and flexible structures for modification. In addition,
      these excellent properties allow the promising in vivo application to real-time
      LNs mapping. Here, we first reported a radiolabeled dual-modal probe based on the
      polythiophene derivative (99mTc-PTP) that was used for LNs mapping with high
      sensitivity and specificity by preoperative single-photon emission computed
      tomography imaging and intraoperative optical guidance. 99mTc-PTP exhibits an
      excellent radio-fluorescence guidance ability and a remarkable biocompatibility
      and holds great potential to be a powerful probe for noninvasive LNs mapping.

PMID- 29373015
TI  - Chemical Approach to Ultrastiff, Strong, and Environmentally Stable Graphene
      Films.
AB  - Reduced graphene oxide (rGO) sheets prepared by a modified Hofmann method (Ho
      rGO) have large graphitic domains with few structural defects, facilitating the
      dense packing between rGO sheets to enhance the mechanical performances of the
      resultant graphene films. Graphene films are fabricated by the filtration of the
      aqueous dispersions of Ho-rGO sheets and further treated by thermal annealing.
      They display high moduli (stiffness) of 54.6 +/- 1.4 GPa and high tensile
      strengths of 521 +/- 19 MPa. They also exhibit high toughness and good electrical
      properties. The intact structure of Ho-rGO sheets narrows the nanochannels in the
      film matrices, greatly reducing the water infiltration into films and providing
      the graphene films with excellent environmental stability. These graphene films
      are attractive for practical applications because of their light weights and
      ultrastiff and ultrastrong mechanical properties.

PMID- 29373017
TI  - Fe(III)-Doped g-C3N4 Mediated Peroxymonosulfate Activation for Selective
      Degradation of Phenolic Compounds via High-Valent Iron-Oxo Species.
AB  - Herein, we proposed a new peroxymonosulfate (PMS) activation system employing the
      Fe(III) doped g-C3N4 (CNF) as catalyst. Quite different from traditional sulfate
      radical-based advanced oxidation processes (SR-AOPs), the PMS/CNF system was
      capable of selectively degrading phenolic compounds (e.g., p-chlorophenol, 4-CP)
      in a wide pH range (3-9) via nonradical pathway. The generated singlet oxygen
      (1O2) in the PMS/CNF3 (3.46 wt % Fe) system played negligible role in removing 4
      CP, and high-valent iron-oxo species fixated in the nitrogen pots of g-C3N4
      (=FeV?O) was proposed as the dominant reactive species by using dimethyl
      sulfoxide as a probe compound. The mechanism was hypothesized that PMS was first
      bound to the Fe(III)-N moieties to generate =FeV?O, which effectively reacted
      with 4-CP via electron transfer. GC-MS analysis indicated that 4-chlorocatechol
      and 1,4-benzoquinone were the major intermediates, which could be further
      degraded to carboxylates. The kinetic results suggested that the formation of
      =FeV?O was proportional to the dosages of PMS and CNF3 under the experimental
      conditions. Also, the PMS/CNF3 system exhibited satisfactory removal of 4-CP in
      the presence of inorganic anions and natural organic matters. We believe that
      this study will provide a new routine for effective PMS activation by
      heterogeneous iron-complexed catalysts to efficiently degrade organic
      contaminants via nonradical pathway.

PMID- 29373016
TI  - Optogenetic Reconstitution for Determining the Form and Function of Membraneless
      Organelles.
AB  - It has recently become clear that large-scale macromolecular self-assembly is a
      rule, rather than an exception, of intracellular organization. A growing number
      of proteins and RNAs have been shown to self-assemble into micrometer-scale
      clusters that exhibit either liquid-like or gel-like properties. Given their
      proposed roles in intracellular regulation, embryo development, and human
      disease, it is becoming increasingly important to understand how these
      membraneless organelles form and to map their functional consequences for the
      cell. Recently developed optogenetic systems make it possible to acutely control
      cluster assembly and disassembly in live cells, driving the separation of
      proteins of interest into liquid droplets, hydrogels, or solid aggregates. Here
      we propose that these approaches, as well as their evolution into the next
      generation of optogenetic biophysical tools, will allow biologists to determine
      how the self-assembly of membraneless organelles modulates diverse biochemical
      processes.

PMID- 29373018
TI  - Sterol Structure Strongly Modulates Membrane-Islet Amyloid Polypeptide
      Interactions.
AB  - Amyloid formation has been implicated in a wide range of human diseases, and the
      interaction of amyloidogenic proteins with membranes are believed to be important
      for many of them. In type-2 diabetes, human islet amyloid polypeptide (IAPP)
      forms amyloids, which contribute to beta-cell death and dysfunction in the
      disease. IAPP-membrane interactions are potential mechanisms of cytotoxicity. In
      vitro studies have shown that cholesterol significantly modulates the ability of
      model membranes to induce IAPP amyloid formation and IAPP-mediated membrane
      damage. It is not known if this is due to the general effects of cholesterol on
      membranes or because of specific sterol-IAPP interactions. The effects of
      replacing cholesterol with eight other sterols/steroids on IAPP binding to model
      membranes, membrane disruption, and membrane-mediated amyloid formation were
      examined. The primary effect of the sterols/steroids on the IAPP-membrane
      interactions was found to reflect their effect upon membrane order as judged by
      fluorescence anisotropy measurements. Specific IAPP-sterol/steroid interactions
      have smaller effects. The fraction of vesicles that bind IAPP was inversely
      correlated with the sterols/steroids' effect on membrane order, as was the extent
      of IAPP-induced membrane leakage and the time to form amyloids. The correlation
      between the fraction of vesicles binding IAPP and membrane leakage was
      particularly tight, suggesting the restriction of IAPP to a subset of vesicles is
      responsible for incomplete leakage.

PMID- 29373019
TI  - Response to Comment on "Visible-Light-Driven Photocatalytic Degradation of
      Organic Water Pollutants Promoted by Sulfite Addition".

PMID- 29373020
TI  - Measurement of Magnetic Exchange in Asymmetric Lanthanide Dimetallics: Toward a
      Transferable Theoretical Framework.
AB  - Magnetic exchange interactions within the asymmetric dimetallic compounds
      [hqH2][Ln2(hq)4(NO3)3].MeOH, (Ln = Er(III) and Yb(III), hqH = 8-hydroxyquinoline)
      have been directly probed with EPR spectroscopy and accurately modeled by spin
      Hamiltonian techniques. Exploitation of site selectivity via doping experiments
      in Y(III) and Lu(III) matrices yields simple EPR spectra corresponding to
      isolated Kramers doublets, allowing determination of the local magnetic
      properties of the individual sites within the dimetallic compounds. CASSCF-SO
      calculations and INS and far-IR measurements are all employed to further support
      the identification and modeling of the local electronic structure for each site.
      EPR spectra of the pure dimetallic compounds are highly featured and correspond
      to transitions within the lowest-lying exchange-coupled manifold, permitting
      determination of the highly anisotropic magnetic exchange between the lanthanide
      ions. We find a unique orientation for the exchange interaction, corresponding to
      a common elongated oxygen bridge for both isostructural analogs. This suggests a
      microscopic physical connection to the magnetic superexchange. These results are
      of fundamental importance for building and validating model microscopic
      Hamiltonians to understand the origins of magnetic interactions between
      lanthanides and how they may be controlled with chemistry.

PMID- 29373021
TI  - Gold Nanoparticle-Based Photoluminescent Nanoswitch Controlled by Host-Guest
      Recognition and Enzymatic Hydrolysis for Arginase Activity Assay.
AB  - The development of simple yet powerful methods for monitoring enzyme activity is
      of great significance. Herein, a facile, convenient, cost-effective, and
      continuous fluorescent method for the detection of arginase and its inhibitor has
      been reported based on a host-guest interaction-controlled and enzymatic
      hydrolysis-controlled luminescent nanoswitch. The fluorescence intensity of 6-aza
      2-thiothymine-stabilized gold nanoparticle (ATT-AuNP) is enhanced by l-arginine,
      owing to the formation of a supramolecular host-guest assembly between the
      guanidine group of l-arginine and ATT molecules capped on the AuNP surface.
      However, hydrolysis of l-arginine, catalyzed by arginase, leads to a decrease in
      the fluorescence intensity of l-arginine/ATT-AuNPs hybrids. Upon incorporation of
      the arginase inhibitor l-norvaline, the fluorescence of the ATT-AuNP-based
      detecting system is restored. The linear range of arginase activity determination
      is from 0.0625 to 1.15 U/mL and the limit of detection is 0.056 U/mL. The half
      maximal inhibition value IC50 of l-norvaline is determined to be 5.6 mM. The
      practicability of this luminescent nanoswitch is validated by assaying the
      arginase activity in rat liver and monitoring the response of rat liver arginase
      to pharmacological agent. Compared to the existing fluorescent method of arginase
      activity assay, the approach demonstrated here does not involve any complicated
      technical manipulation, thereby greatly simplifying the detection steps. We
      propose that this AuNP-based luminescent nanoswitch would find wide applications
      in the field of life sciences and medicine.

PMID- 29373022
TI  - Comment on "Visible-Light-Driven Photocatalytic Degradation of Organic Water
      Pollutants Promoted by Sulfite Addition".

PMID- 29373023
TI  - Understanding Conversion-Type Electrodes for Lithium Rechargeable Batteries.
AB  - The need/desire to lower the consumption of fossil fuels and its environmental
      consequences has reached unprecedented levels in recent years. A global effort
      has been undertaken to develop advanced renewable energy generation and
      especially energy storage technologies, as they would enable a dramatic increase
      in the effective and efficient use of renewable (and often intermittent) energy
      sources. The development of electrical energy storage (EES) technologies with
      high energy and power densities, long life, low cost, and safe use represents a
      challenge from both the fundamental science and technological application points
      of view. While the advent and broad deployment of lithium-ion batteries (LIBs)
      has dramatically changed the EES landscape, their performance metrics need to be
      greatly enhanced to keep pace with the ever-increasing demands imposed by modern
      consumer electronics and especially the emerging automotive markets. Current
      battery technologies are mostly based on the use of a transition metal oxide
      cathode (e.g., LiCoO2, LiFePO4, or LiNiMnCoO2) and a graphite anode, both of
      which depend on intercalation/insertion of lithium ions for operation. While the
      cathode material currently limits the battery capacity and overall energy
      density, there is a great deal of interest in the development of high-capacity
      cathode materials as well as anode materials. Conversion reaction materials have
      been identified/proposed as potentially high-energy-density alternatives to
      intercalation-based materials. However, conversion reaction materials react
      during lithiation to form entirely new products, often with dramatically changed
      structure and chemistry, by reaction mechanisms that are still not completely
      understood. This makes it difficult to clearly distinguish the limitations
      imposed by the mechanism and practical losses from initial particle morphology,
      synthetic approaches, and electrode preparations. Transition metal compounds such
      as transition metal oxides, sulfides, fluorides, phosphides, and nitrides can
      undergo conversion reactions yielding materials with high theoretical capacity
      (generally from 500 to 1500 mA h g-1). In particular, a number of transition
      metal oxides and sulfides have shown excellent electrochemical properties as high
      capacity anode materials. In addition, some transition metal fluorides have shown
      great potential as cathode materials for Li rechargeable batteries. In this
      Account we present mechanistic studies, with emphasis on the use of operando
      methods, of selected examples of conversion-type materials as both potentially
      high-energy-density anodes and cathodes in EES applications. We also include
      examples of the conceptually similar conversion-type reactions involving
      chalcogens and halogens, with emphasis on the Li-S system. In this case we focus
      on the problems arising from the low electrical conductivities of elemental
      sulfur and Li2S and the "redox shuttle" phenomena of polysulfides. In addition to
      mechanistic insights from the use of operando methods, we also cover several key
      strategies in electrode materials design such as controlling the size,
      morphology, composition, and architecture.

PMID- 29373024
TI  - Translocation of Bioactive Molecules through Carbon Nanotubes Embedded in the
      Lipid Membrane.
AB  - One of the major challenges of nanomedicine and gene therapy is the effective
      translocation of drugs and genes across cell membranes. In this study, we
      describe a systematic procedure that could be useful for efficient drug and gene
      delivery into the cell. Using fully atomistic molecular dynamics (MD)
      simulations, we show that molecules of various shapes, sizes, and chemistries can
      be spontaneously encapsulated in a single-walled carbon nanotube (SWCNT) embedded
      in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer, as we
      have exemplified with dendrimers, asiRNA, ssDNA, and ubiquitin protein. We
      compute the free energy gain by the molecules upon their entry inside the SWCNT
      channel to quantify the stability of these molecules inside the channel as well
      as to understand the spontaneity of the process. The free energy profiles suggest
      that all molecules can enter the channel without facing any energy barrier but
      experience a strong energy barrier (?kBT) to translocate across the channel. We
      propose a theoretical model for the estimation of encapsulation and translocation
      times of the molecules. Whereas the model predicts the encapsulation time to be
      of the order of few nanoseconds, which match reasonably well with those obtained
      from the simulations, it predicts the translocation time to be astronomically
      large for each molecule considered in this study. This eliminates the possibility
      of passive diffusion of the molecules through the CNT-nanopore spanning across
      the membrane. To counter this, we put forward a mechanical method of ejecting the
      encapsulated molecules by pushing them with other free-floating SWCNTs of
      diameter smaller than the pore diameter. The feasibility of the proposed method
      is also demonstrated by performing MD simulations. The generic strategy described
      here should work for other molecules as well and hence could be potentially
      useful for drug- and gene-delivery applications.

PMID- 29373025
TI  - Effects of 4-Hydroxyphenyl 4-Isoprooxyphenylsulfone (BPSIP) Exposure on
      Reproduction and Endocrine System of Zebrafish.
AB  - The compound 4-hydroxyphenyl 4-isoprooxyphenylsulfone (BPSIP), a derivative of
      bisphenol S (BPS), has been detected in thermal paper and human urine samples;
      however, its potential effects on the endocrine system are largely unknown. The
      present study was conducted to determine the adverse effects of BPSIP on egg
      production, relative organ weights, plasma levels of sex hormones, and
      transcription of genes related to the hypothalamus-pituitary-gonad (HPG) axis in
      zebrafish (Danio rerio). In male fish, the gonadosomatic index was significantly
      decreased at concentrations of 5 and 50 MUg/L BPSIP. The estrogenic (increase in
      the 17beta-estradiol/testosterone [E2/T] ratio) and antiandrogenic (decrease in
      T) effects were observed in fish exposed to BPSIP and males were more sensitive
      to the adverse effects than females. The changes in sex hormones were supported
      by the regulation of genes along the HPG axis, such as cyp19, 17betahsd, and
      cyp17 transcripts. Although the effective concentration for endocrine disruption
      was greater than that of BPS, the actions of BPSIP on the steroidogenic pathway
      were similar to the effects of BPS exposure.

PMID- 29373026
TI  - Super Strong Be-Be Bonds: Theoretical Insight into the Electronic Structure of Be
      Be Complexes with Radical Ligands.
AB  - The electronic structure of complexes formed by the interaction of Be2 with
      radical ligands (L:Be-Be:L) has been studied by means of the high-level
      theoretical protocol CCSD(T)/cc-pVTZ. At this level of theory, no matter the
      nature of the ligand, the Be-Be bond becomes up to 300 times stronger compared to
      isolated Be2, indicating that these kinds of complexes are thermodynamically
      stable and, thus, that they could be experimentally detected. Moreover, among all
      of the ligands considered, the strength of the Be-Be bond for L = [CN]* was
      calculated to be 330 kJ.mol-1, slightly greater than the strongest up to date L =
      F* complex, thus setting a new mark for the strongest Be-Be bond reported so far
      in the literature. Wave function analysis methods explain this strong interaction
      as a result of the oxidation of the Be2 moiety to Be22+ due to charge transfer
      toward the L ligands. In this study, we have also considered F:Mg-Mg:F complexes,
      which show very similar properties as the ones described for the analogous F:Be
      Be:F.

PMID- 29373027
TI  - Bisannulation of Benzamides and Cyclohexadienone-Tethered Allenes Triggered by
      Cp*Rh(III)-Catalyzed C-H Activation and Relay Ene Reaction.
AB  - The diastereoselective bisannulation of N-(pivaloyloxy)benzamides and
      cyclohexadienone-tethered allenes was accomplished through Cp*Rh(III)-catalyzed C
      H activation and relay ene reaction, providing a 3-isoquinolonyl cis
      hydrobenzofuran framework with high yields and diastereoselectivities. This
      reaction tolerates a wide range of functional groups, enabling further
      conversions to tricyclic and bridged-ring structures. Moreover, the
      dearomatization modification of phenol-contained bioactive molecule is also
      elaborated.

PMID- 29373028
TI  - Orbital Edelstein Effect as a Condensed-Matter Analog of Solenoids.
AB  - We theoretically study current-induced orbital magnetization in a chiral crystal.
      This phenomenon is an orbital version of the Edelstein effect. We propose an
      analogy between the current-induced orbital magnetization and an Ampere field in
      a solenoid in classical electrodynamics. To quantify this effect, we define a
      dimensionless parameter from the response coefficients relating a current density
      with an orbital magnetization. This dimensionless parameter can be regarded as a
      number of turns within a unit cell when the crystal is regarded as a solenoid,
      and it represents how "chiral" the crystal is. By focusing on the dimensionless
      parameter, one can design a band structure that realizes the induction of large
      orbital magnetization. In particular, a Weyl semimetal with all of the Weyl nodes
      close to the Fermi energy can have a large value for this dimensionless
      parameter, which can exceed that of a classical solenoid.

PMID- 29373029
TI  - Nickel-Catalyzed Domino Heck Cyclization/Suzuki Coupling for the Synthesis of 3,3
      Disubstituted Oxindoles.
AB  - The first nickel-catalyzed domino Heck cyclization/Suzuki coupling reaction for
      the synthesis of 3,3-disubstituted oxindoles bearing quaternary all-carbon
      centers is reported. A wide range of electrophiles, such as aryl iodides,
      bromides, triflates, and chlorides, are all compatible with the reaction
      conditions. Moreover, cheap aryl esters, which undergo catalytic C-O bond
      cleavage, could also be employed as electrophiles. The approach shows good yields
      and broad scope, complementing a more practical and sustainable alternative to
      the conventional palladium-based analogues.

PMID- 29373030
TI  - Synthesis of Aromatic Sulfonamides through a Copper-Catalyzed Coupling of
      Aryldiazonium Tetrafluoroborates, DABCO.(SO2)2, and N-Chloroamines.
AB  - A copper-catalyzed aminosulfonylation of aryldiazonium tetrafluoroborates,
      DABCO.(SO2)2, and N-chloroamines is described. This coupling reaction provides an
      efficient and simple approach to a wide range of sulfonamides in moderate to good
      yields under mild conditions. Mechanistic investigation suggests that a radical
      process and transition-metal catalysis are merged in this tandem reaction.

PMID- 29373031
TI  - Photoredox Approach to N-Acyl-N'-aryl-N,N'-aminals Using Enamides and Their
      Conversion to gamma-Lactams.
AB  - A photoredox catalytic approach to synthetically valuable N-acyl-N'-aryl-N,N'
      aminals is described. This method uses the addition of a radical precursor to
      enamides, with subsequent interception of the cationic iminium intermediate with
      an arylamine. The reaction has been shown to be compatible with electron-rich and
      electron-deficient arylamines, and moderate to good levels of
      diastereoselectivity can be attained using a chiral enamide. Furthermore, the N
      acyl-N'-aryl-N,N'-aminal reaction products can be readily cyclized, providing a
      novel synthetic route to valuable gamma-lactams.

PMID- 29373033
TI  - Investigation of Chemical Stability of Dihalogenated Organotelluranes in Organic
      Aqueous Media: The Protagonism of Water.
AB  - The biological activity of tellurium compounds is closely related to the
      tellurium oxidation state or some of their structural features. Hypervalent
      dihalogenated organotelluranes 1-[butyl(dichloro)-lambda4-tellanyl]-2
      (methoxymethyl)benzene (1a) and 1-[butyl(dibromide)-lambda4-tellanyl]-2
      (methoxymethyl)benzene (1b) have been described as inhibitors of proteases
      (cysteine and threonine) and tyrosine phosphatases. However, poor attention has
      been given to their physicochemical properties. Here, a detailed investigation of
      the stability in water of these organotelluranes is reported using 125Te NMR
      analysis. Dihalogenated organotelluranes 1a and 1b were both stable in DMSO- d6
      (from 25 to 75  degrees C), demonstrating their thermal stability. However, the
      addition of a phosphate buffer solution (pH 2-8) to 1a or 1b resulted in an
      immediate conversion to a new Te species, assumed to be the corresponding
      telluroxide. Similar behavior was observed in pure water, demonstrating the low
      chemical stability of these dihalogenated species in the presence of water. These
      results allow concluding that previous biological activity reported for
      dihalogenated organotelluranes 1a and 1b could be attributed to the corresponding
      derivatives from the reaction with water. In the same way as for AS-101, we
      demonstrated that organotelluranes 1a and 1b are not stable in aqueous solution.
      It suggests a proactive role of these organotelluranes in previously reported
      biological activity.

PMID- 29373032
TI  - Tissue Level Diet and Sex-by-Diet Interactions Reveal Unique Metabolite and
      Clustering Profiles Using Untargeted Liquid Chromatography-Mass Spectrometry on
      Adipose, Skeletal Muscle, and Liver Tissue in C57BL6/J Mice.
AB  - Dietary intervention is commonly used for weight loss or to improve health, as
      diet-induced obesity increases the risk of developing type 2 diabetes,
      hypertension, cardiovascular disease, stroke, osteoarthritis, and certain
      cancers. Various dietary patterns are associated with effects on health, yet
      little is known about the effects of diet at the tissue level. Using untargeted
      metabolomics, this study aimed to identify changes in water-soluble metabolites
      in C57BL/6J males and females fed one of five diets (Japanese, ketogenic,
      Mediterranean, American, and standard mouse chow) for 7 months. Metabolite
      abundance was examined in liver, skeletal muscle, and adipose tissue for sex,
      diet, and sex-by-diet interaction. Analysis of variance (ANOVA) suggests that
      liver tissue has the most metabolic plasticity under dietary changes compared
      with adipose and skeletal muscle. The ketogenic diet was distinguishable from
      other diets for both males and females according to partial least-squares
      discriminant analysis. Pathway analysis revealed that the majority of pathways
      affected play an important role in amino acid metabolism in liver tissue. Not
      surprisingly, amino acid profiles were affected by dietary patterns in skeletal
      muscle. Few metabolites were significantly altered in adipose tissue relative to
      skeletal muscle and liver tissue, indicating that it was largely stable,
      regardless of diet alterations. The results of this study revealed that the
      ketogenic diet had the largest effect on physiology, particularly for females.
      Furthermore, metabolomics analysis revealed that diet affects metabolites in a
      tissue-specific manner and that liver was most sensitive to dietary changes.

PMID- 29373034
TI  - Hamigerans R and S: Nitrogenous Diterpenoids from the New Zealand Marine Sponge
      Hamigera tarangaensis.
AB  - Seven new members of the hamigeran family of diterpenoids have been isolated from
      the New Zealand marine sponge Hamigera tarangaensis. Among the new additions are
      hamigeran R (1), considered to be the first benzonitrile-based marine natural
      product, and hamigeran S (2), the first dimeric structure in the series. The
      formation of 1 and 2 is thought to occur via the reaction of hamigeran G with a
      nitrogen source, where the nitrile carbon of 1 is derived from the terpenoid
      skeleton.

PMID- 29373035
TI  - Epithelial Na+ channel differentially contributes to shear stress-mediated
      vascular responsiveness in carotid and mesenteric arteries from mice.
AB  - A potential "new player" in arteries for mediating shear stress responses is the
      epithelial Na+ channel (ENaC). The contribution of ENaC as shear sensor in intact
      arteries, and particularly different types of arteries (conduit and resistance),
      is unknown. We investigated the role of ENaC in both conduit (carotid) and
      resistance (third-order mesenteric) arteries isolated from C57Bl/6J mice. Vessel
      characteristics were determined at baseline (60 mmHg, no flow) and in response to
      increased intraluminal pressure and shear stress using a pressure myograph. These
      protocols were performed in the absence and presence of the ENaC inhibitor
      amiloride (10 uM) and after inhibition of endothelial nitric oxide synthase
      (eNOS) by Nomega-nitro-l-arginine methyl ester (l-NAME; 100 uM). Under no-flow
      conditions, amiloride increased internal and external diameters of carotid (13 +/
      2%, P < 0.05) but not mesenteric (0.5 +/- 0.9%, P > 0.05) arteries. In response
      to increased intraluminal pressure, amiloride had no effect on the internal
      diameter of either type of artery. However, amiloride affected the stress-strain
      curves of mesenteric arteries. With increased shear stress, ENaC-dependent
      effects were observed in both arteries. In carotid arteries, amiloride augmented
      flow-mediated dilation (9.2 +/- 5.3%) compared with control (no amiloride, 6.2 +/
      3.3%, P < 0.05). In mesenteric arteries, amiloride induced a flow-mediated
      constriction (-11.5 +/- 6.6%) compared with control (-2.2 +/- 4.5%, P < 0.05). l
      NAME mimicked the effect of ENaC inhibition and prevented further amiloride
      effects in both types of arteries. These observations indicate that ENaC
      contributes to shear sensing in conduit and resistance arteries. ENaC-mediated
      effects were associated with NO production but may involve different (artery
      dependent) downstream signaling pathways. NEW & NOTEWORTHY The epithelial Na+
      channel (ENaC) contributes to shear sensing in conduit and resistance arteries.
      In conduit arteries ENaC has a role as a vasoconstrictor, whereas in resistance
      arteries ENaC contributes to vasodilation. Interaction of ENaC with endothelial
      nitric oxide synthase/nitric oxide signaling to mediate the effects is supported;
      however, cross talk with other shear stress-dependent signaling pathways cannot
      be excluded.

PMID- 29373036
TI  - TIMP3 deficiency exacerbates iron overload-mediated cardiomyopathy and liver
      disease.
AB  - Chronic iron overload results in heart and liver diseases and is a common cause
      of morbidity and mortality in patients with genetic hemochromatosis and secondary
      iron overload. We investigated the role of tissue inhibitor of metalloproteinase
      3 (TIMP3) in iron overload-mediated tissue injury by subjecting male mice lacking
      Timp3 ( Timp3-/-) and wild-type (WT) mice to 12 wk of chronic iron overload.
      Whereas WT mice with iron overload developed diastolic dysfunction, iron
      overloaded Timp3-/- mice showed worsened cardiac dysfunction coupled with
      systolic dysfunction. In the heart, loss of Timp3 was associated with increased
      myocardial fibrosis, greater Timp1, matrix metalloproteinase ( Mmp) 2, and Mmp9
      expression, increased active MMP-2 levels, and gelatinase activity. Iron overload
      in Timp3-/- mice showed twofold higher iron accumulation in the liver compared
      with WT mice because of constituently lower levels of ferroportin. Loss of Timp3
      enhanced the hepatic inflammatory response to iron overload, leading to greater
      neutrophil and macrophage infiltration and increased hepatic fibrosis. Expression
      of inflammation-related MMPs (MMP-12 and MMP-13) and inflammatory cytokines (IL
      1beta and monocyte chemoattractant protein-1) was elevated to a greater extent in
      iron-overloaded Timp3-/- livers. Gelatin zymography demonstrated equivalent
      increases in MMP-2 and MMP-9 levels in WT and Timp3-/- iron-overloaded livers.
      Loss of Timp3 enhanced the susceptibility to iron overload-mediated heart and
      liver injury, suggesting that Timp3 is a key protective molecule against iron
      mediated pathology. NEW & NOTEWORTHY In mice, loss of tissue inhibitor of
      metalloproteinase 3 ( Timp3) was associated with systolic and diastolic
      dysfunctions, twofold higher hepatic iron accumulation (attributable to
      constituently lower levels of ferroportin), and increased hepatic inflammation.
      Loss of Timp3 enhanced the susceptibility to iron overload-mediated injury,
      suggesting that Timp3 plays a key protective role against iron-mediated
      pathology.

PMID- 29373037
TI  - Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac
      Nrf2 dysregulation in chronic heart failure.
AB  - The imbalance between the synthesis of reactive oxygen species and their
      elimination by antioxidant defense systems results in macromolecular damage and
      disruption of cellular redox signaling, affecting cardiac structure and function,
      thus contributing to contractile dysfunction, myocardial hypertrophy, and
      fibrosis in chronic heart failure [chronic heart failure (CHF)]. The Kelch-like
      ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (Nrf2)
      pathway is an important antioxidant defense mechanism and is closely associated
      with oxidative stress-mediated cardiac remodeling in CHF. In the present study,
      we investigated the regulation of myocardial Nrf2 in the postmyocardial
      infarction (post-MI) state. Six weeks post-MI, Nrf2 protein was downregulated in
      the heart, resulting in a decrease of Nrf2-targeted antioxidant enzymes, whereas
      paradoxically the transcription of Nrf2 was increased, suggesting that
      translational inhibition of Nrf2 may contribute to the dysregulation in CHF. We
      therefore hypothesized that microRNAs may be involved in the translational
      repression of Nrf2 mRNA in the setting of CHF. Using quantitative real-time PCR
      analysis, we found that three microRNAs, including microRNA-27a, microRNA-28-3p,
      and microRNA-34a, were highly expressed in the left ventricle of infarcted hearts
      compared with other organs. Furthermore, in vitro analysis revealed that cultured
      cardiac myocytes and fibroblasts expressed these three microRNAs in response to
      TNF-alpha stimulation. These microRNAs were preferentially incorporated into
      exosomes and secreted into the extracellular space in which microRNA-enriched
      exosomes mediated intercellular communication and Nrf2 dysregulation. Taken
      together, these results suggest that increased local microRNAs induced by MI may
      contribute to oxidative stress by the inhibition of Nrf2 translation in CHF. NEW
      & NOTEWORTHY The results of this work provide a novel mechanism mediated by
      microRNA-enriched exosomes, contributing to the nuclear factor erythroid 2
      related factor 2 dysregulation and subsequent oxidative stress. Importantly,
      these new findings will provide a promising strategy to improve the therapeutic
      efficacy through targeting nuclear factor erythroid 2-related factor 2-related
      microRNAs in the chronic heart failure state, which show potentially clinical
      applications.

PMID- 29373040
TI  - Australian Adolescents and Young Adults-Trends in Cancer Incidence, Mortality,
      and Survival Over Three Decades.
AB  - PURPOSE: Cancer is a significant health concern for adolescents and young adults
      (AYAs; aged 15-24 years). Monitoring population-level changes in incidence,
      mortality, and survival is complicated by the lack of published data presenting
      statistics separately for AYAs. This study synthesizes and reviews data on AYA
      cancers in Australia, including trends in incidence and mortality. METHODS:
      National data were extracted for 1980-2012, primarily from the Australian Cancer
      Database and Australian National Mortality Database. Incidence, mortality, and
      survival trends are described, and incidence and mortality projections are
      reported. RESULTS: In 2000-2009, the annual all-cancer incidence was 31.7 cases
      per 100,000 population, and the mortality rate was 4.1 per 100,000. Incidence,
      mortality, and survival varied widely, indicating areas of concern. Melanoma was
      the most common cancer, and bone cancer had the highest mortality and poorest
      survival rates. All-cancer incidence rates peaked in the late 1990s, but then
      declined, largely due to melanoma. All-cancer mortality decreased throughout the
      study period, but showed no improvements for some common sites (i.e., brain,
      bone, soft tissue). Further reductions in all-cancer incidence and mortality are
      projected for the next decade, although specific cancers (colorectal cancers and
      lymphomas) were projected to increase in incidence. CONCLUSIONS: Observed
      Australian cancer trends are largely consistent with trends for other high-income
      populations. While overall decreases in incidence and mortality are encouraging,
      consistently high mortality and poor survival for some cancers remain concerning.
      Planned data initiatives for AYAs with cancer will aid in resolving whether
      trends continue and projections are realized in the future.

PMID- 29373039
TI  - Contraceptive Method Choice Among Young Adults: Influence of Individual and
      Relationship Factors.
AB  - Because decisions related to contraceptive behavior are often made by young
      adults in the context of specific relationships, the relational context likely
      influences use of contraceptives. Data presented here are from in-person
      structured interviews with 536 Black, Hispanic, and White young adults from East
      Los Angeles, California. We collected partner-specific relational and
      contraceptive data on all sexual partnerships for each individual, on four
      occasions, over one year. Using three-level multinomial logistic regression
      models, we examined individual and relationship factors predictive of
      contraceptive use. Results indicated that both individual and relationship
      factors predicted contraceptive use, but factors varied by method. Participants
      reporting greater perceived partner exclusivity and relationship commitment were
      more likely to use hormonal/long-acting methods only or a less effective
      method/no method versus condoms only. Those with greater participation in sexual
      decision making were more likely to use any method over a less effective
      method/no method and were more likely to use condoms only or dual methods versus
      a hormonal/long-acting method only. In addition, for women only, those who
      reported greater relationship commitment were more likely to use hormonal/long
      acting methods or a less effective method/no method versus a dual method. In
      summary, interactive relationship qualities and dynamics (commitment and sexual
      decision making) significantly predicted contraceptive use.

PMID- 29373038
TI  - Actin polymerization contributes to enhanced pulmonary vasoconstrictor reactivity
      after chronic hypoxia.
AB  - Chronic hypoxia (CH) augments basal and endothelin-1 (ET-1)-induced pulmonary
      vasoconstrictor reactivity through reactive oxygen species (ROS) generation and
      RhoA/Rho kinase (ROCK)-dependent myofilament Ca2+ sensitization. Because ROCK
      promotes actin polymerization and the actin cytoskeleton regulates smooth muscle
      tension, we hypothesized that actin polymerization is required for enhanced basal
      and ET-1-dependent vasoconstriction after CH. To test this hypothesis, both end
      points were monitored in pressurized, endothelium-disrupted pulmonary arteries
      (fourth-fifth order) from control and CH (4 wk at 0.5 atm) rats. The actin
      polymerization inhibitors cytochalasin and latrunculin attenuated both basal and
      ET-1-induced vasoconstriction only in CH vessels. To test whether CH directly
      alters the arterial actin profile, we measured filamentous actin (F-actin)-to
      globular actin (G-actin) ratios by fluorescent labeling of F-actin and G-actin in
      fixed pulmonary arteries and actin sedimentation assays using homogenized
      pulmonary artery lysates. We observed no difference in actin polymerization
      between groups under baseline conditions, but ET-1 enhanced actin polymerization
      in pulmonary arteries from CH rats. This response was blunted by the ROS
      scavenger tiron, the ROCK inhibitor fasudil, and the mDia (RhoA effector)
      inhibitor small-molecule inhibitor of formin homology domain 2. Immunoblot
      analysis revealed an effect of CH to increase both phosphorylated (inactive) and
      total levels of the actin disassembly factor cofilin but not phosphorylated
      cofilin-to-total cofilin ratios. We conclude that actin polymerization
      contributes to increased basal pulmonary arterial constriction and ET-1-induced
      vasoconstrictor reactivity after CH in a ROS- and ROCK-dependent manner. Our
      results further suggest that enhanced ET-1-mediated actin polymerization after CH
      is dependent on mDia but independent of changes in the phosphorylated cofilin-to
      total cofilin ratio. NEW & NOTEWORTHY This research is the first to demonstrate a
      role for actin polymerization in chronic hypoxia-induced basal pulmonary arterial
      constriction and enhanced agonist-induced vasoconstrictor activity. These results
      suggest that a reactive oxygen species-Rho kinase-actin polymerization signaling
      pathway mediates this response and may provide a mechanistic basis for the
      vasoconstrictor component of pulmonary hypertension.

PMID- 29373041
TI  - What Predicts Exercise Maintenance and Well-Being? Examining The Influence of
      Health-Related Psychographic Factors and Social Media Communication.
AB  - Habitual exercising is an important precursor to both physical and psychological
      well-being. There is, thus, a strong interest in identifying key factors that can
      best motivate individuals to sustain regular exercise regimen. In addition to the
      importance of psychographic factors, social media use may act as external
      motivator by allowing users to interact and communicate about exercise. In this
      study, we examined the influence of health consciousness, health-oriented
      beliefs, intrinsic motivation, as willingness to communicate about health on
      social media, social media activity on exercise, and online social support on
      exercise maintenance and well-being on a sample of 532 American adults. Employing
      structural equation modeling, we found that health-oriented beliefs mediated the
      effect of health consciousness on intrinsic motivation which in turn was a
      significant predictor of exercise maintenance. Exercise maintenance significantly
      predicted both physical and psychological well-being. Extrinsic motivators, as
      measured by willingness to communicate about health on social media, social media
      activity on exercise, and online social support did not however significantly
      influence exercise maintenance. These findings have implications for the design
      and implementation of exercise-promoting interventions by identifying underlying
      factors that influence exercise maintenance.

PMID- 29373042
TI  - A Test of The Risk Perception Attitude Framework as a Message Tailoring Strategy
      to Promote Diabetes Screening.
AB  - The risk perception attitude (RPA) framework was tested as a message tailoring
      strategy to encourage diabetes screening. Participants (N = 602) were first
      categorized into one of four RPA groups based on their diabetes risk and efficacy
      perceptions and then randomly assigned to receive a message that matched their
      RPA, mismatched their RPA, or a control message. Participants receiving a matched
      message reported greater intentions to engage in self-protective behavior than
      participants who received a mismatched message or the control message. The
      results also showed differences in attitudes and behavioral intentions across the
      four RPA groups. Participants in the responsive group had more positive attitudes
      toward diabetes screening than the other three groups, whereas participants in
      the indifferent group reported the weakest intentions to engage in self
      protective behavior.

PMID- 29373043
TI  - Expired Epinephrine Maintains Chemical Concentration and Sterility.
AB  - OBJECTIVES: Epinephrine shortages affect nearly all American emergency medical
      services (EMS) systems. Utilization of expired epinephrine could mitigate this
      situation in daily EMS operations. Concerns about using expired medications
      include sterility, potency, and potential harmful chemical decay byproducts.
      There are no cross-platform analyses of sterility and chemical purity of multiple
      samples of expired parenteral epinephrine. We hypothesized that epinephrine
      injections will remain sterile and will retain their active ingredient's content
      for more than 30 months past expiration. METHODS: Six parenteral epinephrine
      prefilled syringes, 1 mg/10 mL, with an expiration date of January 1, 2012 had
      been stored in the climate controlled setting of a hospital inpatient pharmacy
      where they remained until they were taken for chemical or microbial analysis 30
      months after expiration. An unexpired parenteral epinephrine prefilled syringe
      content was used as a control. Contents of three separate syringes with expired
      content from the same lot and one control underwent ultra-high pressure liquid
      chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR)
      to determine epinephrine content and stability. In parallel, contents of another
      three expired epinephrine syringes were analyzed for sterility by plating on
      aerobic, anaerobic, and fungal media in a hospital microbiology laboratory. The
      aerobic plates were checked for growth in 3 days, the anaerobic in 5 days, and
      the fungal in 28 days. RESULTS: UHPLC-MS and NMR showed that content of
      epinephrine present in the original sample remained unchanged compared to the
      control. There was no statistical difference in the UHPLC-MS and NMR signal
      amplitudes between the control and the expired samples. No chemical degradation
      byproducts were detected using NMR. There was no growth of any bacteria or
      fungus. CONCLUSION: Recurrent epinephrine shortages impact EMS and hospital
      operations in the United States. Individual administrators may be hesitant to
      authorize use of expired pharmaceuticals due to perceived potential complications
      or fear of litigation. This study shows that the original parenteral epinephrine
      remains sterile and detectably pure more than 2.5 years after expiration. Further
      study of the sterility and chemical integrity of expired medications that had
      been subjected to the conditions of EMS vehicles may be a future research
      endeavor based on the aforementioned paradigm.

PMID- 29373044
TI  - Interactive Effect between On-Scene Hypoxia and Hypotension on Hospital Mortality
      and Disability in Severe Trauma.
AB  - BACKGROUND: It is unclear whether effect size of the hypoxia is different on in
      hospital mortality and disability according to hypotension status in the field.
      METHODS: Adult severe trauma (ST) patients during 2012-13 who were treated by
      emergency medical services (EMS) and had abnormal revised trauma scores in the
      field or who had positive trauma triage criteria were analyzed. Exposure was
      hypoxia (<94%) measured by EMS. End points were hospital mortality and disability
      defined as a Glasgow Outcome Scale that decreased by 2 points or more.
      Multivariable logistic regression with interaction model between hypoxia and
      hypotension was used for outcomes to calculate the adjusted odds ratios (AOR)
      with 95% confidence intervals (95% CIs) after adjusting for potential
      confounders. RESULTS: A total of 17,406 EMS-ST patients were analyzed. Of those,
      2,598 (14.9%) died, and 3,292 (21.5%) were considered disabled at discharge. The
      total hypoxia group showed higher mortality and disability indices (35.7 and
      51.2%) than the non-hypoxia group (10.7 and 15.9%) (each p-value < 0.0001). The
      AOR of hypoxia was 2.15 (1.92-2.40) for mortality and was 1.97 (1.75-2.21) for
      disability. In the interaction model, AORs for mortality by hypoxia in the
      hypotensive and non-hypotensive groups were 2.66 (2.32-3.04) and 1.74 (1.61
      1.87), respectively (P < 0.0001 for interaction). The AORs for disability in the
      hypotensive and non-hypotensive groups were 2.17 (1.87-2.53) and 1.55 (1.42
      1.69), respectively (P < 0.0001 for interaction). CONCLUSIONS: The effect of
      hypoxia was much greater in the hypotensive group than in the non-hypotensive
      group both in terms of mortality and disability.

PMID- 29373045
TI  - Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and
      sensitization of angiotensin II-induced hypertension in adult offspring.
AB  - Accumulating evidence indicates that maternal high-fat diet (HFD) is associated
      with metabolic syndrome and cardiovascular disease in adult offspring. The
      present study tested the hypothesis that maternal HFD modulates the brain renin
      angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that
      alter angiotensin II (ANG II) and TNF-alpha actions and sensitize the ANG II
      elicited hypertensive response in adult offspring. All offspring were cross
      fostered by dams on the same or opposite diet to yield the following four groups:
      offspring from normal-fat control diet-fed dams suckled by control diet-fed dams
      (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a
      HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group).
      RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated
      upregulation of mRNA expression of several RAS components, NADPH oxidase, and
      proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during
      either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring
      also showed decreased cardiac baroreflex sensitivity and increased pressor
      responses to intracerebroventricular microinjection of either ANG II or TNF
      alpha. Furthermore, chronic systemic infusion of ANG II resulted in enhanced
      upregulation of mRNA expression of RAS components, NADPH oxidase, and
      proinflammatory cytokines in the lamina terminalis and paraventricular nucleus
      and an augmented hypertensive response in the OHC, OCH, and OHH groups compared
      with the OCC group. The results suggest that maternal HFD blunts cardiac
      baroreflex function and enhances pressor responses to ANG II or proinflammatory
      cytokines through upregulation of the brain RAS, oxidative stress, and
      inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal
      high-fat diet during either pregnancy or lactation is sufficient for perinatal
      programming of sensitization for hypertension, which is associated with
      hyperreactivity of central cardiovascular nuclei that, in all likelihood,
      involves elevated expression of the renin-angiotensin system, NADPH oxidase, and
      proinflammatory cytokines. The present study demonstrates, for the first time,
      the central mechanism underlying maternal high-fat diet sensitization of the
      hypertensive response in adult offspring.

PMID- 29373046
TI  - Comparative Evaluation of Using NOTA and DOTA Derivatives as Bifunctional
      Chelating Agents in the Preparation of 68Ga-Labeled Porphyrin: Impact on
      Pharmacokinetics and Tumor Uptake in a Mouse Model.
AB  - PURPOSE: Both NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid) and DOTA
      (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) derivatives have been
      used as bifunctional chelating agents (BFCAs) for the preparation of 68Ga-labeled
      target-specific agents having potential for positron emission tomography (PET)
      imaging of cancerous lesions. In the present work, the authors have attempted a
      comparative pharmacokinetic evaluation between 68Ga-labeled porphyrins prepared
      using NOTA and DOTA derivatives as the BFCAs. PROCEDURES: A symmetrical porphyrin
      derivative, 5,10,15,20-tetrakis(p-carboxymethyleneoxyphenyl)porphyrin, was
      synthesized and coupled with two different BFCAs viz. p-NH2-benzyl-NOTA and p-NH2
      benzyl-DOTA. Both the porphyrin-BFCA conjugates were radiolabeled with 68Ga. A
      comparative bioevaluation involving pharmacokinetics and tumor affinity was
      performed in a tumor-bearing small animal model. RESULTS: Gallium-68-labeled
      porphyrin-amido-benzyl-NOTA and porphyrin-amido-benzyl-DOTA complexes were
      prepared with high radiochemical purity. Both radiolabeled complexes exhibited
      almost similar stability in human serum and near-identical tumor affinity and
      pharmacokinetic behavior in animal studies. CONCLUSION: The present study
      demonstrates that the pharmacokinetic behavior of 68Ga-labeled porphyrin
      derivatives, prepared using either NOTA or DOTA derivatives as BFCAs, remains
      almost identical and hence both NOTA and DOTA derivatives could be considered
      equivalent for developing 68Ga-based PET agents for imaging of tumorous lesions.

PMID- 29373047
TI  - The study of surface electromyography used for the assessment of abductor
      hallucis muscle activity in patients with hallux valgus.
AB  - BACKGROUND: Hallux valgus is a common foot disorder. In patients with hallux
      valgus, the anatomy and biomechanics of foot is subject to alterations.
      OBJECTIVE: The aim of this clinical and neurophysiological study is to compare
      the activity of abductor hallucis (AbdH) muscle between the group of patients
      with hallux valgus and control group of healthy people, with the use of surface
      electromyography. METHODS: The study involved 44 feet with diagnosed hallux
      valgus (research group) and 42 feet without deformation (control group). The X
      ray images, measurements of range of motion in the first metatarsophalangeal
      joint and in hallux interphalangeal joint, and the surface electromyography study
      recorded from AbdH muscle were performed. RESULTS: Considering the amplitude of
      motor unit action potential, study participants with hallux valgus demonstrate
      significantly less activity of AbdH muscle than people without hallux valgus
      deformity. This activity is not dependent on the severity of valgus, age, or
      range of motion. CONCLUSIONS: It is speculated that the changes of the AbdH
      function may occur in the period before clinical appearance of hallux valgus
      deformity, or at the onset of distortion development. Further studies are needed
      for a comprehensive assessment of AbdH muscle in patients with hallux valgus.

PMID- 29373049
TI  - Predicting Short- and Long-Term Mating Orientations: The Role of Sex and the Dark
      Tetrad.
AB  - Previous literature has extensively considered factors that influence short- and
      long-term mating orientations, with specific attention given to individual
      differences (e.g., sex and personality). Although research has established the
      role "darker" personality traits (i.e., the dark triad) play in mating
      orientation, this triad has recently been reconceptualized as a tetrad. Due to
      this reconceptualization, the current study sought to establish the utility of
      sex and the dark tetrad in predicting individual short- and long-term mating
      orientations. In addition, as an alternative to previous methodology, the
      orientations were assessed using a continuous measure. A total of 464
      participants, ages 18 to 69, completed an online questionnaire assessing dark
      tetrad traits and mating orientations. Results showed that sex, trait
      psychopathy, and trait sadism were significant predictors of a short-term mating
      orientation. For long-term mating orientations, there was no predictive utility
      of sex, but there were positive associations for narcissism and negative
      associations for psychopathy and sadism. These findings add further understanding
      of the predictors of mating orientation and the utility of the tetrad in
      predicting mating orientations. In addition, the findings offer future mating
      orientation studies an alternative measure to the traditional dichotomous format.

PMID- 29373048
TI  - Role of TGF-beta activated kinase-1 inhibitor on the interaction between
      macrophages and mesangial cells on the condition of high glucose.
AB  - OBJECTIVE: To investigate the effect of TGF-beta activated kinase-1(TAK1)
      inhibitor 5Z-7-oxozeaenol on the interaction between macrophages and mesangial
      cells exposed to high glucose. METHODS: The macrophages and mesangial cells were
      cultured separately or co-cultured and divided into seven groups: inhibitor
      control group, mannitol control group, normal control group, high glucose group
      and inhibitor groups. The expression of p-TAK1, TAK1 binding protein (TAB1),
      transcription factor NF - kappa B (NF-kappaB p65) of macrophages were analyzed by
      Western blotting. The intracellular localization of NF-kappaB p65 was analyzed by
      immunofluorescence. The levels of inflammation cytokines and extracellular matrix
      were determined by enzyme-linked immune sorbent assay. Migration of macrophages
      was observed by microscope. RESULTS: Compared with control group, the expression
      of p-TAK1, TAB1, NF-kappaB p65 were significantly higher in high glucose group (P
      < 0.05). Both in co-culture group and single culture group, the levels of
      inflammation cytokines and extracellular matrix (P < 0.05) in high glucose group
      were higher than that in control group. Exposed to high glucose, the levels of
      inflammation cytokines and extracellular matrix in co-cultured group were higher
      than that in single culture group (P < 0.05). 5Z-7-oxozeaenol can decrease those
      cytokines secretion, comparing with high glucose group (P < 0.05). The number of
      macrophages migration were decreased by 5Z-7-oxozeaenol (P < 0.05). CONCLUSION:
      Exposed to high glucose, macrophages and mesangial cells can interact with each
      other to promote the secretion of inflammation cytokines and extracellular
      matrix. TAK1 inhibitor can reduce the secretion of inflammation cytokines and
      extracellular matrix components by intervening NF-kappaB p65 nuclear transfer and
      inhibiting macrophage migration.

PMID- 29373050
TI  - Diagnostic Accuracy of the CASI-4R Psychosis Subscale for Children Evaluated in
      Pediatric Outpatient Clinics.
AB  - Diagnostic accuracy of the Diagnostic and Statistical Manual of Mental Disorders
      oriented Child and Adolescent Symptom Inventory (CASI-4R) Psychotic Symptoms
      scale was tested using receiver operating characteristic analyses to identify
      clinically significant psychotic symptoms. Participants were new outpatients (N =
      700), ages 6.0 to 12.9 years (M = 9.7, SD = 1.8) at 9 child outpatient mental
      health clinics, who participated in the Longitudinal Assessment of Manic Symptoms
      (LAMS) Study baseline assessment. Because LAMS undersampled participants with low
      mania scores by design, present analyses weighted low scorers to produce unbiased
      estimates. Psychotic symptoms, operationally defined as a score of 3 or more for
      hallucinations or 4 or more for delusions based on the Schedule for Affective
      Disorders and Schizophrenia (K-SADS) psychosis items, occurred in 7% of youth. K
      SADS diagnoses for those identified with psychotic symptoms above threshold
      included major depressive disorder, bipolar spectrum disorder, attention
      deficit/hyperactivity disorder, posttraumatic stress disorder, psychotic
      disorders, and autism spectrum disorder. The optimal psychosis screening cut
      score (maximizing sensitivity and specificity) was 2.75+ (corresponding
      diagnostic likelihood ratio [DiLR] = 4.29) for the parent version and 3.50+ (DiLR
      = 5.67) for the teacher version. The Area under the Curve for parent and teacher
      report was .83 and .74 (both p < .001). Parent report performed significantly
      better than teacher report for identifying psychotic symptoms above threshold (p
      = .03). The CASI-4R Psychosis subscale (J) appears clinically useful for
      identifying psychotic symptoms in children because of its brevity and accuracy.

PMID- 29373051
TI  - Self-Perceived Physical Attractiveness in Relation to Scars Among Adolescent and
      Young Adult Cancer Survivors: A Population-Based Study.
AB  - OBJECTIVE: Cancer treatment may result in various effects that last long after
      treatment has been concluded. The purpose of this study was to explore to what
      extent scars affect adolescents and young adults postcancer treatment. METHODS:
      In this population-based study, a study-specific questionnaire was developed by a
      method used in several previous investigations carried out by our research group,
      Clinical Cancer Epidemiology. Question development involved expert validation by
      professionals from oncology units, midwives, epidemiologists, and statisticians.
      The questionnaire was developed in collaboration with adolescent and young adult
      cancer survivors. The topics covered in the questionnaire were as follows:
      psychosocial health, body image and sexuality, fertility, education, work, and
      leisure. The web-based questionnaire was sent to teenage and young adult cancer
      survivors and matched controls in Sweden. RESULTS: In this study, the relative
      risk of feeling less attractive due to scars was higher both for female cancer
      survivors RR 1.48, CI 1.05-2.08 and male cancer survivors RR 1.90, CI 1.15-3.13
      compared to controls. The feeling of attractiveness was negatively related to the
      size of scars in both cancer and control groups. In a logistic regression
      analysis, significant associations were found between age, education, exercise,
      depression, and the feeling of low attractiveness due to scars. CONCLUSIONS: The
      results of this study provide a basis for care interventions for teenage and
      young adult cancer patients during and after cancer treatment. Further research
      is needed on care interventions to reduce, if possible, the impact of scars.

PMID- 29373052
TI  - Methylenetetrahydrofolate reductase C677T polymorphism and diabetic retinopathy.

PMID- 29373053
TI  - The Status-Health Paradox: Organizational Context, Stress Exposure, and Well
      being in the Legal Profession.
AB  - Prior research evaluates the health effects of higher status attainment by
      analyzing highly similar individuals whose circumstances differ after some
      experience a "status boost." Advancing that research, we assess health
      differences across organizational contexts among two national samples of lawyers
      who were admitted to the bar in the same year in their respective countries. We
      find that higher-status lawyers in large firms report more depression than lower
      status lawyers, poorer health in the American survey, and no health advantage in
      Canada. Adjusting for income exacerbates these patterns-were it not for their
      higher incomes, large-firm lawyers would have a greater health disadvantage.
      Last, we identify two stressors in the legal profession, overwork and work-life
      conflict, that are more prevalent in the private sector and increase with firm
      size. Adjusting for these stressors explains well-being differences across
      organizational contexts. This study documents the role of countervailing
      mechanisms in health inequality research.

PMID- 29373055
TI  - Strategies for Inclusion, 3rd Edition By Lauren J. Lieberman and Cathy Houston
      Wilson.

PMID- 29373054
TI  - Erratum.

PMID- 29373057
TI  - Athletic Training Service Characteristics for Patients With Ankle Sprains
      Sustained During High School Athletics.
AB  - CONTEXT:   Limited information exists on the amount and type of care provided by
      athletic trainers (ATs) treating athletes who sustained ankle sprains in the high
      school setting. OBJECTIVE:   To describe AT services provided for patients with
      ankle sprains injured in high school athletics. DESIGN:   Descriptive
      epidemiology study. SETTING:   Athletic training facility (ATF) visits and AT
      services collected from 147 high schools in 26 states. PATIENTS OR OTHER
      PARTICIPANTS:   High school student-athletes participating in 13 boys' and 14
      girls' sports who sustained a diagnosed ankle sprain during the 2011-2012 through
      2013-2014 academic years. The ATs documented 3213 ankle sprains. MAIN OUTCOME
      MEASURE(S):   Number of ATF visits and individual AT services and mean ATF visits
      (per injury) and AT services (per injury) were calculated by sport and for time
      loss injuries (participation-restriction time of at least 24 hours) and non-time
      loss injuries (participation-restriction time <24 hours). RESULTS:   During the 3
      year period, 19 925 ATF visits were reported, with an average of 6 (interquartile
      range = 1-7) ATF visits per ankle sprain. Most ATF visits were for non-time-loss
      injuries (65.1%). Football accounted for the largest proportions of ankle sprains
      (27.3%) and ATF visits (35.0%). In total, 71 404 AT services were provided for
      ankle sprains. Therapeutic activities or exercise were the most common AT
      services (47.4%), followed by neuromuscular reeducation (16.6%), strapping
      (14.2%), and modalities (11.5%). An average of 22 (interquartile range = 4-28) AT
      services were reported per ankle sprain. The average number of AT services per
      injury was higher among patients with time-loss than non-time-loss injuries (35
      versus 19; P < .001). CONCLUSIONS:   The ATs provided a variety of services to
      treat high school athletes who had sustained ankle sprains, including therapeutic
      exercises and neuromuscular reeducation, which were supported by research.
      However, ATs should consider using manual therapy (use supported by grade B
      evidence) and therapeutic exercise more (use supported by grade A evidence).

PMID- 29373056
TI  - Linear Acceleration in Direct Head Contact Across Impact Type, Player Position,
      and Playing Scenario in Collegiate Women's Soccer Players.
AB  - CONTEXT:   Heading, an integral component of soccer, exposes athletes to a large
      number of head impacts over a career. The literature has begun to indicate that
      cumulative exposure may lead to long-term functional and psychological deficits.
      Quantifying an athlete's exposure over a season is a first step in understanding
      cumulative exposure. OBJECTIVE:   To measure the frequency and magnitude of
      direct head impacts in collegiate women's soccer players across impact type,
      player position, and game or practice scenario. DESIGN:   Cross-sectional study.
      SETTING:   National Collegiate Athletic Association Division I institution.
      PATIENTS OR OTHER PARTICIPANTS:   Twenty-three collegiate women's soccer
      athletes. MAIN OUTCOME MEASURE(S):   Athletes wore Smart Impact Monitor
      accelerometers during all games and practices. Impacts were classified during
      visual, on-field monitoring of athletic events. All direct head impacts that
      exceeded the 10 g threshold were included in the final data analysis. The
      dependent variable was linear acceleration, and the fixed effects were (1) type
      of impact: clear, pass, shot, unintentional deflection, or head-to-head contact;
      (2) field position: goalkeeper, defense, forward, or midfielder; (3) playing
      scenario: game or practice. RESULTS:   Shots (32.94 g +/- 12.91 g, n = 38; P =
      .02) and clears (31.09 g +/- 13.43 g, n = 101; P = .008) resulted in higher mean
      linear accelerations than passes (26.11 g +/- 15.48 g, n = 451). Head-to-head
      impacts (51.26 g +/- 36.61 g, n = 13; P < .001) and unintentional deflections
      (37.40 g +/- 34.41 g, n = 24; P = .002) resulted in higher mean linear
      accelerations than purposeful headers (ie, shots, clears, and passes). No
      differences were seen in linear acceleration across player position or playing
      scenario. CONCLUSIONS:   Nonheader impacts, including head-to-head impacts and
      unintentional deflections, resulted in higher mean linear accelerations than
      purposeful headers, including shots, clears, and passes, but occurred
      infrequently on the field. Therefore, these unanticipated impacts may not add
      substantially to an athlete's cumulative exposure, which is a function of both
      frequency and magnitude of impact.

PMID- 29373058
TI  - A Functional Return-to-Play Progression After Exertional Heat Stroke in a High
      School Football Player.
AB  - OBJECTIVE:   To present a functional return-to-play (RTP) progression after
      exertional heat stroke (EHS) in a 17-year-old high school football defensive end
      (height = 185 cm, mass = 145.5 kg). BACKGROUND:   The patient had no pertinent
      medical history but moved to a warm climate several days before the EHS occurred.
      After completing an off-season conditioning test (14- * 110-yd [12.6- * 99.0-m]
      sprints) on a warm afternoon (temperature = approximately 34 degrees C [93
      degrees F], relative humidity = 53%), the patient collapsed. An athletic trainer
      (AT) was called to the field, where he found the patient conscious but exhibiting
      central nervous system dysfunction. Emergency medical services were summoned and
      immediately transported the patient to the hospital. DIFFERENTIAL DIAGNOSIS:  
      Exertional heat stroke, heat exhaustion, exertional sickling, rhabdomyolysis, and
      cardiac arrhythmia. TREATMENT:   The patient was immediately transported to a
      hospital, where his oral temperature was 39.6 degrees C (103.3 degrees F). He was
      transferred to a children's hospital and treated for rhabdomyolysis,
      transaminitis, and renal failure. He was hospitalized for 11 days. After a
      physician's clearance once the laboratory results normalized, an RTP progression
      was completed. The protocol began with light activity and progressed over 3 weeks
      to full football practice. During activity, an AT monitored the patient's
      gastrointestinal temperature, heart rate, rating of perceived exertion, fluid
      consumption, and sweat losses. UNIQUENESS:   Documentation of RTP guidelines for
      young athletes is lacking. We used a protocol intended for the football setting
      to ensure the athlete was heat tolerant, had adequate physical fitness, and could
      safely RTP. Despite his EHS, he recovered fully, with no lasting effects, and
      successfully returned to compete in the final 5 games of the season. CONCLUSIONS:
      Using a gradual RTP progression and close monitoring, a high school defensive
      end successfully returned to football practice and games after EHS. This case
      demonstrates the feasibility of implementing a safe RTP protocol after EHS and
      may serve as a guide to ATs working in the high school setting. This case also
      highlights the need for more research in this area.

PMID- 29373061
TI  - Cirripede Cypris Antennules: How Much Structural Variation Exists Among
      Balanomorphan Species from Hard-Bottom Habitats?
AB  - Barnacle cypris antennules are important for substratum attachment during
      settlement and on through metamorphosis from the larval stage to sessile adult.
      Studies on the morphology of cirripede cyprids are mostly qualitative, based on
      descriptions from images obtained using a scanning electron microscope (SEM). To
      our knowledge, our study is the first to use scanning electron microscopy to
      quantify overall structural diversity in cypris antennules by measuring 26
      morphological parameters, including the structure of sensory organs. We analyzed
      cyprids from seven species of balanomorphan barnacles inhabiting rocky shore
      communities; for comparison, we also included a sponge-inhabiting balanomorphan
      and a verrucomorphan species. Multivariate analysis of the structural parameters
      resulted in two distinct clusters of species. From nonmetric multidimensional
      scaling plots, the sponge-inhabiting Balanus spongicola and Verruca stroemia
      formed one cluster, while the other balanomorphan species, all from hard bottoms,
      grouped together in the other cluster. The shape of the attachment disk on
      segment 3 is the key parameter responsible for the separation into two clusters.
      The present results show that species from a coastal hard-bottom habitat may
      share a nearly identical antennular structure that is distinct from barnacles
      from other habitats, and this finding supports the fact that such species also
      have rather similar reactions to substratum cues during settlement. Any
      differences that may be found in settlement biology among such species must
      therefore be due either to differences in the properties of their adhesive
      mechanisms or to the way that sensory stimuli are detected by virtually identical
      setae and processed into settlement behavior by the cyprid.

PMID- 29373062
TI  - Eastern Oysters Crassostrea virginica Produce Plastic Morphological Defenses in
      Response to Crab Predators Despite Resource Limitation.
AB  - Many prey react to predation risk by altering their phenotype to reduce their
      chances of being consumed but incur reductions in growth and fecundity when
      reacting to predators. To determine when to produce defenses, prey collect
      information and evaluate the costs and benefits of defense induction. Resource
      availability can affect prey ability and willingness to incur defense costs. When
      resources are scarce, defenses may suffer disproportionate decreases in energy
      allocation if defenses would further reduce prey access to resources or if
      resources are needed to maintain metabolic functions. We tested the effects of
      predation risk and resource availability on plastic defenses in eastern oysters
      Crassostrea virginica and present novel findings that oysters continued to
      produce defended shells in response to predators when resources were limited,
      even though they grew smaller, lighter shells when deprived of food in control
      conditions. Predation risk affected all three tested shell metrics (area, weight,
      and strength), but food availability did not. Although low food levels often
      limit expression of predator defenses, predator cues caused oysters to build
      shells that were larger and heavier, with a similar trend for shell strength, in
      treatments with both low and high food levels, suggesting that predation is an
      important pressure in this system. The differences between predator and control
      treatments were greater under conditions of low food availability, and thus,
      resource availability may influence interpretations of plastic responses to
      predators.

PMID- 29373060
TI  - Comparison of Compressive Myofascial Release and the Graston Technique for
      Improving Ankle-Dorsiflexion Range of Motion.
AB  - CONTEXT:   Restricted dorsiflexion (DF) at the ankle joint can cause acute and
      chronic injuries at the ankle and knee. Myofascial release and instrument
      assisted soft tissue mobilization (IASTM) techniques have been used to increase
      range of motion (ROM); however, evidence directly comparing their effectiveness
      is limited. OBJECTIVE:   To compare the effects of a single session of
      compressive myofascial release (CMR) or IASTM using the Graston Technique (GT) on
      closed chain ankle-DF ROM. DESIGN:   Randomized controlled trial. SETTING:  
      Laboratory. PATIENTS OR OTHER PARTICIPANTS:   Participants were 44 physically
      active people (53 limbs) with less than 30 degrees  of DF. INTERVENTION(S):  
      Limbs were randomly assigned to 1 of 3 groups: control, CMR, or GT. Both
      treatment groups received one 5-minute treatment that included scanning the area
      and treating specific restrictions. The control group sat for 5 minutes before
      measurements were retaken. MAIN OUTCOME MEASURE(S):   Standing and kneeling ankle
      DF were measured before and immediately after treatment. Change scores were
      calculated for both positions, and two 1-way analyses of variance were conducted.
      RESULTS:   A difference between groups was found in the standing ( F2,52 = 13.78,
      P = .001) and kneeling ( F2,52 = 5.85, P = .01) positions. Post hoc testing
      showed DF improvements in the standing position after CMR compared with the GT
      and control groups (both P = .001). In the kneeling position, DF improved after
      CMR compared with the control group ( P = .005). CONCLUSIONS:   Compressive
      myofascial release increased ankle DF after a single treatment in participants
      with DF ROM deficits. Clinicians should consider adding CMR as a treatment
      intervention for patients with DF deficits.

PMID- 29373063
TI  - Growing Safe: Acute Size Escape from Desiccation in Juvenile Crepipatella
      peruviana (Mollusca: Gastropoda).
AB  - Desiccation is an important limiting factor in the intertidal zone. Generally
      decreasing seaward, desiccation stress can also be alleviated in wet
      microhabitats. Juvenile snails are generally more susceptible to desiccation than
      adults, and, for some species, juveniles must therefore hide in microhabitats to
      survive emersion. The transition from hiding in safe microhabitats to being able
      to survive fully exposed for the duration of low tide is not well documented. In
      this study, we investigated the influence of size on desiccation tolerance in
      juveniles of the calyptraeid gastropod Crepipatella peruviana to determine the
      size at which they can first survive exposure to air. Juveniles 2-13 mm long were
      exposed to 75% or 100% relative humidity for 0.5-6.5 hours. Juveniles smaller
      than 5 mm in shell length did not survive emersion at 75% relative humidity for
      even 0.5 hours; surprisingly, most also perished after short exposures to air at
      100% relative humidity, suggesting that something other than desiccation stress
      may also be at play. In marked contrast, 82% of juveniles larger than 6 mm in
      shell length survived exposure to 75% relative humidity for the full 6.5 hours.
      In a field survey, no juveniles smaller than 9 mm were found on exposed rock but
      rather were found only in wet microhabitats. We suggest that the clearly defined
      size escape from desiccation may reflect a change in gill functioning or a
      newfound ability to retain water more effectively within the mantle cavity at low
      tide.

PMID- 29373059
TI  - Dynamic Varus and the Development of Iliotibial Band Syndrome.
AB  - CONTEXT:   Although the risk of osteoarthritis development after acute knee
      injury has been widely studied, the long-term consequences of knee overuse injury
      are not well understood. OBJECTIVE:   To identify the relationship between gait
      related risk factors associated with osteoarthritis and the development of
      iliotibial band syndrome (ITBS) in members of a single University Army Reserve
      Officers' Training Corps unit. DESIGN:   Prospective cohort study. SETTING:  
      Biomechanics laboratory. PATIENTS OR OTHER PARTICIPANTS:   Sixty-eight cadets
      undergoing standardized physical fitness training. INTERVENTION(S):   Three
      dimensional lower extremity kinematics (240 Hz) and kinetics (960 Hz) were
      collected for 3 bilateral trials during shod running at 4.0 m/s +/- 10%. Injury
      tracking was conducted for 7 months of training. MAIN OUTCOME MEASURE(S):  
      Biomechanical variables, including varus thrust and knee-adduction moment, were
      compared between the injured and control groups. RESULTS:   Twenty-six cadets
      with no history of overuse injury served as the control group, whereas 6 cadets
      (7 limbs) who developed ITBS that required them to modify their training program
      or seek medical care (or both) served as the injured group. Maximum varus
      velocity was higher ( P = .006) and occurred sooner during stance ( P = .04) in
      the injured group than in the control group, indicating greater varus thrust.
      Maximum knee-varus angle and maximum knee-adduction moment were higher ( P = .02
      and P = .002, respectively) and vertical stiffness was lower ( P = .03) in the
      injured group. CONCLUSIONS:   Measures of dynamic varus stability appeared to be
      altered in individuals who developed ITBS. Biomechanical knee variables
      previously identified as increasing the risk for knee osteoarthritis were also
      associated with the development of ITBS in healthy adults.

PMID- 29373064
TI  - Natural Variation in Responses to Acute Heat and Cold Stress in a Sea Anemone
      Model System for Coral Bleaching.
AB  - Rising ocean temperatures disrupt the symbiosis between corals and their
      microalgae, accelerating global decline of coral reef ecosystems. Because of the
      difficulty of performing laboratory experiments with corals, the sea anemone
      Aiptasia has emerged as an important model system for molecular studies of coral
      bleaching and symbiosis. Here, we investigate natural variation in bleaching
      responses among different genetic lineages of Aiptasia. Both heat- and cold
      induced paths to symbiosis breakdown were analyzed. Significant genetic variation
      in response to acute heat stress was observed, with severe bleaching of two
      Aiptasia strains from Hawaii but minimal bleaching of strains from the U.S. South
      Atlantic, including the strain used to generate the Aiptasia reference genome.
      Both strains from Hawaii hosted Symbiodinium type B1, whereas strains from the
      U.S. South Atlantic hosted type A4 or B2. In contrast to the results from
      exposures to acute heat stress, negligible variation was observed in response to
      a pulsed cold shock despite moderate bleaching across all strains. These results
      support our hypothesis that bleaching responses to distinct stressors are
      independent. Our findings emphasize the role of stress regime when predicting
      adaptive responses of symbiotic cnidarians to changing climates, because genetic
      variation may exist for some forms of stress-induced bleaching but not others.

PMID- 29373066
TI  - About the Cover.

PMID- 29373065
TI  - Differences in Larval Arm Movements Correlate with the Complexity of Musculature
      in Two Phylogenetically Distant Echinoids, Eucidaris tribuloides (Cidaroidea) and
      Lytechinus variegatus (Euechinoidea).
AB  - Within a common body plan, echinoid planktotrophic larvae are morphologically
      diverse, with variations in overall size, the length, and number of arms and the
      presence or absence of epidermal structures. In this report, we are interested in
      variation in larval arm-flexing behavior and correlated differences in larval
      musculature. Larvae of the cidaroid Eucidaris tribuloides exhibit conspicuous and
      regular arm-flexing behavior. In contrast, Lytechinus variegatus, a
      representative of the euechinoid clade, does not exhibit this behavior. We
      hypothesized that there were differences in musculature that correlated with this
      behavioral contrast and compared the development and structure of larval muscles
      between these species. We report substantial differences in some aspects of
      larval musculature. In addition to previously described oral musculature, both
      larvae possessed polygon-shaped musculature at the basal end of the larva.
      However, larval musculature in E. tribuloides was larger and contained additional
      muscles not observed in larvae of L. variegatus. Therefore, a conspicuous larval
      behavior consisting of repeated flexing of the postoral and posterodorsal larval
      arms was correlated with a larger, more complex musculature. This simple contrast
      indicates that larval musculature not associated with endoderm evolves in a
      manner that relates to differences in larval behavior and that additional
      comparisons are warranted.

PMID- 29373067
TI  - Role of TRP Channels in Dinoflagellate Mechanotransduction.
AB  - Transient receptor potential (TRP) ion channels are common components of
      mechanosensing pathways, mainly described in mammals and other multicellular
      organisms. To gain insight into the evolutionary origins of eukaryotic
      mechanosensory proteins, we investigated the involvement of TRP channels in
      mechanosensing in a unicellular eukaryotic protist, the dinoflagellate
      Lingulodinium polyedra. BLASTP analysis of the protein sequences predicted from
      the L. polyedra transcriptome revealed six sequences with high similarity to
      human TRPM2, TRPM8, TRPML2, TRPP1, and TRPP2; and characteristic TRP domains were
      identified in all sequences. In a phylogenetic tree including all mammalian TRP
      subfamilies and TRP channel sequences from unicellular and multicellular
      organisms, the L. polyedra sequences grouped with the TRPM, TPPML, and TRPP
      clades. In pharmacological experiments, we used the intrinsic bioluminescence of
      L. polyedra as a reporter of mechanoresponsivity. Capsaicin and RN1734, agonists
      of mammalian TRPV, and arachidonic acid, an agonist of mammalian TRPV, TRPA,
      TRPM, and Drosophila TRP, all stimulated bioluminescence in L. polyedra.
      Mechanical stimulation of bioluminescence, but not capsaicin-stimulated
      bioluminescence, was inhibited by gadolinium (Gd3+), a general inhibitor of
      mechanosensitive ion channels, and the phospholipase C (PLC) inhibitor U73122.
      These pharmacological results are consistent with the involvement of TRP-like
      channels in mechanosensing by L. polyedra. The TRP channels do not appear to be
      mechanoreceptors but rather are components of the mechanotransduction signaling
      pathway and may be activated via a PLC-dependent mechanism. The presence and
      function of TRP channels in a dinoflagellate emphasize the evolutionary
      conservation of both the channel structures and their functions.

PMID- 29373068
TI  - Upregulation and Nuclear Location of MMP28 in Alveolar Epithelium of Idiopathic
      Pulmonary Fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive aging-associated
      disease of unknown etiology. A growing body of evidence indicates that aberrant
      activated alveolar epithelial cells induce the expansion and activation of the
      fibroblast population, leading to the destruction of the lung architecture. Some
      matrix metalloproteinases (MMPs) are upregulated in IPF, indicating that they may
      be important in the pathogenesis and/or progression of IPF. In the present study,
      we examined the expression of MMP28 in this disease and evaluated its functional
      effects in two alveolar epithelial cell lines and in human primary bronchial
      epithelial cells. We found that the enzyme is expressed in bronchial (apical and
      cytoplasmic localization) and alveolar (cytoplasmic and nuclear localization)
      epithelial cells in two different groups of patients with IPF. In vitro MMP28
      epithelial silencing decreased the proliferation rate and delayed wound closing,
      whereas overexpression showed opposite effects, protecting from apoptosis and
      enhanced epithelial-mesenchymal transition. Our findings demonstrate that MMP28
      is upregulated in epithelial cells from IPF lungs, where it may play a role in
      increasing the proliferative and migratory phenotype in a catalysis-dependent
      manner.

PMID- 29373069
TI  - Preferences for Communicating about Breast Cancer Screening Among
      Racially/Ethnically Diverse Older Women.
AB  - Differences exist across breast cancer screening guidelines regarding frequency
      of screening and age of discontinuation for older women (>=70 years) at average
      risk for breast cancer. These differences highlight concerns about the benefits
      and harms of screening, and may negatively impact older women's ability to make
      informed screening decisions. This study examined preferences for communicating
      about screening mammography among racially/ethnically diverse, older women. In
      depth interviews were conducted with 59 women with no breast cancer history. Non
      proportional quota sampling ensured roughly equal numbers on age (70-74 years,
      >=75 years), race/ethnicity (non-Hispanic/Latina White, non-Hispanic/Latina
      Black, Hispanic/Latina), and education (<=high school diploma, >high school
      diploma). Interviews were audio-recorded, transcribed, and analyzed using NVivo
      10. Thematic analyses revealed that rather than being told to get mammograms,
      participants wanted to hear about the benefits and harms of screening
      mammography, including overdiagnosis. Participants recommended that this
      information be communicated via physicians or other healthcare providers,
      included in brochures/pamphlets, and presented outside of clinical settings
      (e.g., in senior groups). Results were consistent regardless of participants'
      age, race/ethnicity, or education. Findings revealed that older women desire
      information about the benefits and harms of screening mammography, and would
      prefer to learn this information through discussions with healthcare providers
      and multiple other formats.

PMID- 29373070
TI  - Lipolysis-Stimulating Peptide from Soybean Protects Against High Fat Diet-Induced
      Apoptosis in Skeletal Muscles.
AB  - Obesity is generally associated with low-grade chronic inflammation that involves
      the recruitment of macrophages and other inflammation factors to the adipocytes
      of obese individuals. Tumor necrosis factor-alpha (TNF-alpha), a cytokine
      associated with systemic inflammation, is elevated in conditions of obesity. TNF
      alpha is an important factor that plays an important role in skeletal muscle
      wasting. Apoptosis of myonuclei contributes to the loss of muscle mass and
      therefore plays an important role in skeletal muscle atrophy. In mouse models
      that were fed a high fat diet (HFD), a lipolysis-stimulating peptide-VHVV
      (purified from hydrolysate resulting from flavourzyme treatment of soy protein)
      was found to reduce HFD-related apoptotic effects in mice skeletal muscle and
      potentially control atrophy. HFD fed mice had heavier body weight than those fed
      with normal chow, and VHVV administration restricted lipid accumulation in muscle
      tissues of mice fed with HFD but increased nutrient uptake. Moreover, specific
      concentrations of VHVV regulated TNF-alpha expression that was elevated by HFD,
      suppressed apoptosis-related proteins and regulated the proteins of lipid
      metabolism.

PMID- 29373071
TI  - Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative
      Breast Cancer.
AB  - Purpose Studies suggest that a subset of patients with triple-negative breast
      cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit
      from an AR inhibitor. This phase II study evaluated the antitumor activity and
      safety of enzalutamide in patients with locally advanced or metastatic AR
      positive TNBC. Patients and Methods Tumors were tested for AR with an
      immunohistochemistry assay optimized for breast cancer; nuclear AR staining > 0%
      was considered positive. Patients received enzalutamide 160 mg once per day until
      disease progression. The primary end point was clinical benefit rate (CBR) at 16
      weeks. Secondary end points included CBR at 24 weeks, progression-free survival,
      and safety. End points were analyzed in all enrolled patients (the intent-to
      treat [ITT] population) and in patients with one or more postbaseline assessment
      whose tumor expressed >= 10% nuclear AR (the evaluable subgroup). Results Of 118
      patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to
      33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable
      subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7
      months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the
      evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months
      to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to
      not yet reached) in the evaluable subgroup. Fatigue was the only treatment
      related grade 3 or higher adverse event with an incidence of > 2%. Conclusion
      Enzalutamide demonstrated clinical activity and was well tolerated in patients
      with advanced AR-positive TNBC. Adverse events related to enzalutamide were
      consistent with its known safety profile. This study supports additional
      development of enzalutamide in advanced TNBC.

PMID- 29373072
TI  - Cytokinins and the CRE1 receptor influence endogenous gibberellin levels in
      Medicago truncatula.
AB  - Gibberellins (GAs) and cytokinins (CKs) are hormones that play antagonistic roles
      in several developmental processes in plants. However, there has been little
      exploration of their reciprocal interactions. Recent work in Medicago truncatula
      has revealed that GA signalling can regulate CK levels and response in roots.
      Here, we examine the reciprocal interaction, by assessing how CKs and the CRE1
      (Cytokinin Response 1) CK receptor may influence endogenous GA levels. Real-Time
      RT-PCR analyses revealed that the expression of key GA biosynthesis genes is
      regulated in response to a short-term CK treatment and requires the CRE1
      receptor. Similarly, GA quantifications indicated that a short-term CK treatment
      decreases the GA1 pool in wild-type plants and that GA levels are increased in
      the cre1 mutant compared to the wild-type. These data suggest that the M.
      truncatula CRE1-dependent CK signaling pathway negatively regulates bioactive GA
      levels.

PMID- 29373074
TI  - Gizzard Helminths in Female Northern Pintails ( Anas acuta) Wintering Along the
      Texas Coast.
AB  - Gizzard helminths were examined in 100 (50 adult, 50 juvenile) female northern
      pintails ( Anas acuta). Sixty-three individual helminths, representing 5 species
      ( Amidostomum acutum, Echinuria uncinata, Epomidiostomum uncinatum, Streptocara
      crassicauda, and Gastrotaenia cygni) were found. Twenty-seven northern pintails
      were infected with 1-3 helminth species and averaged 1.4 species. Overall, A.
      acutum and G. cygni were the most prevalent and abundant species (20%, n = 31 and
      10%, n = 25, respectively), followed by S. crassicauda (5%, n = 5), E. uncinata
      (1%, n = 1), and E. uncinatum (1%, n = 1). Intensity of infection for A. acutum,
      E. uncinata, E. uncinatum, S. crassicauda, and G. cygni was 1.6 +/- 0.3 [SE], 1.0
      +/- 0, 1.0 +/- 0, 1.0 +/- 0, and 2.5 +/- 0.6, respectively. Our findings
      represent new information about gizzard helminth infections in northern pintails
      wintering along the Texas coast.

PMID- 29373073
TI  - Transcriptional profiling reveals gland-specific differential expression in the
      three major salivary glands of the adult mouse.
AB  - RNA-Seq was used to better understand the molecular nature of the biological
      differences among the three major exocrine salivary glands in mammals.
      Transcriptional profiling found that the adult murine parotid, submandibular, and
      sublingual salivary glands express greater than 14,300 protein-coding genes, and
      nearly 2,000 of these genes were differentially expressed. Principle component
      analysis of the differentially expressed genes revealed three distinct clusters
      according to gland type. The three salivary gland transcriptomes were dominated
      by a relatively few number of highly expressed genes (6.3%) that accounted for
      more than 90% of transcriptional output. Of the 912 transcription factors
      expressed in the major salivary glands, greater than 90% of them were detected in
      all three glands, while expression for ~2% of them was enriched in an individual
      gland. Expression of these unique transcription factors correlated with
      sublingual and parotid specific subsets of both highly expressed and
      differentially expressed genes. Gene ontology analyses revealed that the highly
      expressed genes common to all glands were associated with global functions, while
      many of the genes expressed in a single gland play a major role in the function
      of that gland. In summary, transcriptional profiling of the three murine major
      salivary glands identified a limited number of highly expressed genes,
      differentially expressed genes, and unique transcription factors that represent
      the transcriptional signatures underlying gland-specific biological properties.

PMID- 29373075
TI  - Trpv4 involvement in the sex differences in blood pressure regulation in
      spontaneously hypertensive rats.
AB  - Arterial pressure (AP) is lower in premenopausal women than in men of a similar
      age. Premenopausal women exhibit a lower sympathetic activity and a greater
      baroreceptor reflex; however, mechanisms controlling sex differences in blood
      pressure regulation are not well understood. We hypothesized that different
      neuronal functions in the cardiovascular centers of the brains of men and women
      may contribute to the sex difference in cardiovascular homeostasis. Our previous
      studies on male spontaneously hypertensive rats (SHRs) and their normotensive
      counterparts, Wistar Kyoto (WKY) rats, revealed that the gene-expression profile
      of the nucleus tractus solitarius (NTS), a region of the medulla oblongata that
      is pivotal for regulating the set point of AP, is strongly associated with AP.
      Thus, we hypothesized that gene-expression profiles in the rat NTS are related to
      sex differences in AP regulation. Because female SHRs clearly exhibit lower AP
      than their male counterparts of a similar age, we investigated whether SHR NTS
      exhibits sex differences in gene expression by using microarray and RT-qPCR
      experiments. The transcript for transient receptor potential cation channel
      subfamily V member 4 ( Trpv4) was found to be upregulated in SHR NTS in females
      compared with that in males. The channel was expressed in neurons and glial cells
      within NTS. The TRPV4 agonist 4-alpha-phorbol-12,13-didecanoate (4alpha-PDD)
      decreased blood pressure when injected into NTS of rats. These findings suggest
      that altered TRPV4 expression might be involved in the sex differences in blood
      pressure regulation.

PMID- 29373077
TI  - Genetics of fasting and postprandial metabolite levels are overlapping.
AB  - In 2015, a genome-wide association study described 59 independent signals that
      showed strong associations with 85 fasting metabolite concentrations as measured
      by the Biocrates AbsoluteIDQ p150 kit. However, the human body resides in a
      nonfasting state for the greater part of the day, and the genetic basis of
      postprandial metabolite concentrations remains largely unknown. We systematically
      examined these previously identified genetic associations in postprandial
      metabolite concentrations after a mixed meal. Of these 85 metabolites, 23 were
      identified with significant changes after the meal, for which 38 gene-metabolite
      associations were analyzed. Of these 38 associations, 31 gene-metabolite
      associations were replicated with postprandial metabolite concentrations. These
      data indicate that the genetics of fasting and postprandial metabolite levels are
      significantly overlapping.

PMID- 29373078
TI  - Molecular Detection of Theileria annulata in Cattle from Different Regions of
      Punjab, Pakistan, by Using Recombinase Polymerase Amplification and Polymerase
      Chain Reaction.
AB  - Piroplasmosis is one of the most important diseases of livestock, constraining
      optimal production and leading to economic loss. This study was carried out to
      detect Theileria annulata by using 2 different molecular techniques: recombinase
      polymerase amplification (RPA) and conventional polymerase chain reaction (PCR).
      Blood samples were collected from 274 ticks infesting asymptomatic cattle from
      several counties in the Chakwal, Faisalabad, and Jhang districts of Punjab
      Province in Pakistan by using FTA cards. After extraction of genomic DNA, each
      sample was subjected to RPA optimized to amplify a 281-bp fragment of the Enolase
      gene for T. annulata. The specificity of the test was confirmed using positive
      DNA samples of related piroplasm species, whereas the analytical sensitivity was
      calculated using different serial dilutions of a long fragment of the same gene.
      The RPA results were positive for 48 (17.51%) of 274 samples. All 274 samples
      were screened using conventional PCR, and 21 (7.66%) samples were positive for T.
      annulata. All the samples that were RPA positive but PCR negative were sequenced,
      which confirmed the results of RPA. The highest positive rate was found in
      Chakwal district, followed by Faisalabad and Jhang districts. This study
      demonstrates the application of highly sensitive and specific rapid diagnostic
      methods for T. annulata to a regional screening program. This is the first report
      of tick-borne disease from Pakistan by using RPA.

PMID- 29373079
TI  - Carotid body: a metabolic sensor implicated in insulin resistance.
AB  - The carotid body is now looked at as a multipurpose sensor for blood gases, blood
      pH, and several hormones. The matter of glucose sensing by the carotid body has
      been debated for several years in the literature, and these days there is a
      consensus that carotid body activity is modified by metabolic factors that
      contribute to glucose homeostasis. However, the sensing ability for glucose is
      still being pondered: are the carotid bodies low glucose sensors or, in contrast,
      are they overresponsive in high-glucose conditions? Herein, we debate the glucose
      and insulin sensing capabilities of the carotid body as key early events in the
      overactivation of the carotid body, which is increasingly recognized as an
      important feature of metabolic diseases. Additionally, we dedicate a final
      section to discuss new outside-the-box therapies designed to decrease carotid
      body activity that may be used for treating metabolic diseases.

PMID- 29373081
TI  - The effect of sex and localised fatigue on triceps surae musculoarticular
      stiffness.
AB  - PURPOSE: The main purpose of this study was to investigate the influence of
      fatigue on musculoarticular stiffness (MAS) of the ankle joint across sexes.
      METHODS: Twenty-seven males and 26 females participated in the study. After
      baseline assessment of MAS and related variables, localised fatigue was induced
      in triceps surae using the standing heel-rise test during which the subjects were
      instructed to lift and drop the heel at a frequency of 0.5 Hz. When subjects were
      unable to continue due to exhaustion the test was terminated and another MAS test
      was performed soon after. RESULTS: Significant higher triceps surae MAS was found
      in men compared to women (p < .01). MAS decreased (p < .01) between pre- and post
      fatigue on average from 18.0 to 17.0 KN m-1 and from 14.5 to 13.9 KN m-1 in men
      and women, respectively. Percentage changes revealed, however, that in relative
      terms the changes in all the variables evaluated were similar (p > .01) between
      sexes, with MAS less than 5%. CONCLUSION: Despite the sex-related differences at
      baseline, fatigue seems to affect biomechanical properties of the ankle joint
      similarly in men and women.

PMID- 29373076
TI  - Rat models of 17beta-estradiol-induced mammary cancer reveal novel insights into
      breast cancer etiology and prevention.
AB  - Numerous laboratory and epidemiologic studies strongly implicate endogenous and
      exogenous estrogens in the etiology of breast cancer. Data summarized herein
      suggest that the ACI rat model of 17beta-estradiol (E2)-induced mammary cancer is
      unique among rodent models in the extent to which it faithfully reflects the
      etiology and biology of luminal types of breast cancer, which together constitute
      ~70% of all breast cancers. E2 drives cancer development in this model through
      mechanisms that are largely dependent upon estrogen receptors and require
      progesterone and its receptors. Moreover, mammary cancer development appears to
      be associated with generation of oxidative stress and can be modified by multiple
      dietary factors, several of which may attenuate the actions of reactive oxygen
      species. Studies of susceptible ACI rats and resistant COP or BN rats provide
      novel insights into the genetic bases of susceptibility and the biological
      processes regulated by genetic determinants of susceptibility. This review
      summarizes research progress resulting from use of these physiologically relevant
      rat models to advance understanding of breast cancer etiology and prevention.

PMID- 29373083
TI  - Gut microbiome may contribute to insulin resistance and systemic inflammation in
      obese rodents: a meta-analysis.
AB  - A number of studies have associated obesity with altered gut microbiota, although
      results are discordant regarding compositional changes in the gut microbiota of
      obese animals. Herein we used a meta-analysis to obtain an unbiased evaluation of
      structural and functional changes of the gut microbiota in diet-induced obese
      rodents. The raw sequencing data of nine studies generated from high-fat diet
      (HFD)-induced obese rodent models were processed with QIIME to obtain gut
      microbiota compositions. Biological functions were predicted and annotated with
      KEGG pathways with PICRUSt. No significant difference was observed for alpha
      diversity and Bacteroidetes-to-Firmicutes ratio between obese and lean rodents.
      Bacteroidia, Clostridia, Bacilli, and Erysipelotrichi were dominant classes, but
      gut microbiota compositions varied among studies. Meta-analysis of the nine
      microbiome data sets identified 15 differential taxa and 57 differential pathways
      between obese and lean rodents. In obese rodents, increased abundance was
      observed for Dorea, Oscillospira, and Ruminococcus, known for fermenting
      polysaccharide into short chain fatty acids (SCFAs). Decreased Turicibacter and
      increased Lactococcus are consistent with elevated inflammation in the obese
      status. Differential functional pathways of the gut microbiome in obese rodents
      included enriched pyruvate metabolism, butanoate metabolism, propanoate
      metabolism, pentose phosphate pathway, fatty acid biosynthesis, and glycerolipid
      metabolism pathways. These pathways converge in the function of carbohydrate
      metabolism, SCFA metabolism, and biosynthesis of lipid. HFD-induced obesity
      results in structural and functional dysbiosis of gut microbiota. The altered gut
      microbiome may contribute to obesity development by promoting insulin resistance
      and systemic inflammation.

PMID- 29373082
TI  - Artificial intelligence, physiological genomics, and precision medicine.
AB  - Big data are a major driver in the development of precision medicine. Efficient
      analysis methods are needed to transform big data into clinically-actionable
      knowledge. To accomplish this, many researchers are turning toward machine
      learning (ML), an approach of artificial intelligence (AI) that utilizes modern
      algorithms to give computers the ability to learn. Much of the effort to advance
      ML for precision medicine has been focused on the development and implementation
      of algorithms and the generation of ever larger quantities of genomic sequence
      data and electronic health records. However, relevance and accuracy of the data
      are as important as quantity of data in the advancement of ML for precision
      medicine. For common diseases, physiological genomic readouts in disease
      applicable tissues may be an effective surrogate to measure the effect of genetic
      and environmental factors and their interactions that underlie disease
      development and progression. Disease-applicable tissue may be difficult to
      obtain, but there are important exceptions such as kidney needle biopsy
      specimens. As AI continues to advance, new analytical approaches, including those
      that go beyond data correlation, need to be developed and ethical issues of AI
      need to be addressed. Physiological genomic readouts in disease-relevant tissues,
      combined with advanced AI, can be a powerful approach for precision medicine for
      common diseases.

PMID- 29373084
TI  - Immunization with a Mixture of Nucleoprotein from Human Metapneumovirus and
      AbISCO-100 Adjuvant Reduces Viral Infection in Mice Model.
AB  - The human metapneumovirus (hMPV) is the second leading cause globally of acute
      infection of the respiratory tract in children, infecting the upper and lower
      airways. The hMPV may induce an inappropriate Th2-type immune response, which
      causes severe pulmonary inflammation, leading to the obstruction of airways.
      Despite its severe epidemiological relevance, no vaccines are currently available
      for the prevention of hMPV-induced illness. In this investigation, we
      demonstrated that immunization of mice with the recombinant hMPV nucleoprotein
      (hMPV-N) mixed with the AbISCO-100 adjuvant reduced viral replication in lungs
      following challenge with the virus. We found that immunized mice had reduced
      weight loss, decreased granulocytes in the lung, an increased level of specific
      nucleoprotein antibodies of IgG1 and IgG2a-isotypes, and a local profile of
      Th1/Th17-type cytokines. Our results suggest that immunization with the hMPV-N
      and the AbISCO-100 adjuvant induces a reduction of viral infection and could be
      considered for the development of an hMPV vaccine.

PMID- 29373085
TI  - Spread of Vancomycin-Resistant Enterococcus faecium Isolates Despite Validated
      Infection Control Measures in an Italian Hospital: Antibiotic Resistance and
      Genotypic Characterization of the Endemic Strain.
AB  - An alarming increase of vancomycin-resistant Enterococcus faecium (VREfm)
      isolates was detected in an Italian referral hospital subjected to policies of
      infection control validated by the Joint Commission International. Analysis of
      the population structure of 122 consecutive, nonreplicate VREfm isolates
      collected over an 18-month period identified a single major clone that spread
      around the whole hospital, rapidly establishing an endemic state. It belonged to
      sequence type (ST) 17 and showed a highly multidrug-resistant phenotype, being
      resistant to all antimicrobial classes for the carriage of several resistance
      determinants. Furthermore, some strains with decreased susceptibility to
      daptomycin were detected. Eighteen out of the 122 isolates did not group in the
      major clone. They showed a low spreading potential inside the hospital wards,
      even if most of them displayed a multidrug-resistant phenotype and belonged to a
      hospital-adapted lineage. Causes that led to the VREfm endemic state have not
      been fully elucidated. However, it is conceivable that the increase in systemic
      antibiotic consumption and the use of selective digestive tract decontamination,
      including vancomycin in critically ill patients during the period before 2014,
      may have played a role in the ST17 clone dissemination, but additional traits
      conferring high fitness in hospital environment cannot be excluded.

PMID- 29373086
TI  - Influenza Virus: Dealing with a Drifting and Shifting Pathogen.
AB  - Numerous modern technological and scientific advances have changed the vaccine
      industry. However, nearly 70 years of influenza vaccine usage have passed without
      substantial changes in the underlying principles of the vaccine. The challenge of
      vaccinating against influenza lies in the constantly changing nature of the virus
      itself. Influenza viruses undergo antigenic evolution through antigenic drift and
      shift in their surface glycoproteins. This has forced frequent updates of vaccine
      antigens to ensure that the somewhat narrowly focused vaccine-induced immune
      responses defend against circulating strains. Few vaccine production systems have
      been developed that can entertain such constant changes. Although influenza virus
      infection induces long-lived immunologic memory to the same or similar strains,
      most people do not encounter the same strain repeatedly in their lifespan,
      suggesting that enhancement of natural immunity is required to improve influenza
      vaccines. It is clear that transformative change of influenza vaccines requires a
      rethink of how we immunize. In this study, we review the problems associated with
      the changing nature of the virus, and highlight some of the approaches being
      employed to improve influenza vaccines.

PMID- 29373087
TI  - An Outbreak of NDM-1-Producing Klebsiella pneumoniae, Associated with OmpK35 and
      OmpK36 Porin Loss in Tunisia.
AB  - OBJECTIVES: To describe clinical and molecular characteristics of an outbreak due
      to metallo-beta-lactamases (MBLs) producing Klebsiella pneumoniae collected at
      Charles Nicolle Hospital of Tunis and to analyze the impact of outer membrane
      porin (OMP) loss on carbapenem resistance levels. METHODS: Between 2010 and 2015,
      178 carbapenem-resistant Enterobacteriaceae were isolated. Screening for MBL
      production was performed using combined disk diffusion method, with imipenem and
      ethylene diamine tetraacetic acid (EDTA) as inhibitors. Resistance genes and
      virulence factors were identified by polymerase chain reaction (PCR) and
      sequencing. Genotyping was performed by pulsed-field gel electrophoresis and
      multilocus sequence typing. Genetic environment of carbapenemase genes was
      determined by PCR mapping. Conjugation assays were performed, and plasmids were
      assigned to incompatibility groups by PCR-based replicon typing. OMPs were
      profiled by sodium dodecyl sulfate-polyacrilamide gel electrophoresis, and porin
      genes were sequenced. RESULTS: Nineteen K. pneumoniae (10.6%) showing MBL
      activity were isolated from patients hospitalized on four different wards. NDM-1
      was the only MBL identified, in association with blaOXA-48. All strains lacked at
      least one OMP, and carbapenem resistance levels were remarkably elevated in
      strains lacking OmpK35 and OmpK36. blaNDM-1 was located in IncFIA-type
      conjugative plasmid, with the same genetic context in all strains. The
      epidemiological diffusion of blaNDM-1 was due to two clones, one major clone
      belonging to sequence type (ST) 147 (n = 16) and the other clone belonging to
      ST307 (n = 3). CONCLUSIONS: This study describes an outbreak of NDM-1-producing
      K. pneumoniae strains, isolated from a Tunisian hospital, caused by two clones
      belonging to ST147 and ST307; and highlights the role of OMPs loss, in
      combination with beta-lactamase expression, in conferring high carbapenem
      resistance.

PMID- 29373088
TI  - Molecular Characterization and Clonal Diversity of Methicillin-Resistant and 
      Susceptible Staphylococcus aureus Isolates of Milk of Cows with Clinical Mastitis
      in Tunisia.
AB  - The aim of this study was to determine the genetic lineages, and the frequency of
      antibiotic resistance and virulence determinants in methicillin-resistant
      Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus (MSSA)
      isolates recovered from milk of cows with clinical mastitis. Three hundred milk
      samples from bovine with clinical mastitis were obtained from 30 dairy farms in
      different regions of Tunisia. Fifteen of the 300 tested samples contained S.
      aureus (5%), in three cases were MRSA. Isolates (one/sample) were typed (S.
      aureus protein A [spa], multilocus sequence typing and accessory gene regulator
      [agr]). The presence of resistance and virulence genes was analyzed by PCR. The
      three MRSA isolates contained mecA and blaZ genes (one of them also the msr(A)
      gene), and carried the enterotoxin gene sen; they were typed as t10381-ST4114 or
      t267-ST4120, and corresponded to agr type-I. Twelve MSSA isolates were recovered
      and harbored the blaZ (7 strains) or erm(C) genes (1 strain). The MSSA isolates
      presented seven different spa-types, associated to new sequence types (STs): t426
      ST4118, t267-ST4120, t1773-ST4115, t509-ST4119, t529-ST4117, t2844-ST4113, and
      t2802-ST4112; most isolates (8/12) were typed as t267/ST4120. All S. aureus
      isolates were scn-negative, except one MSSA of lineage ST4119 that exhibited the
      immune evasion cluster type D, and harbored the seg, sei, sem, seo, and seu
      enterotoxin genes. Four MSSA isolates carried the toxic shock syndrome toxin 1
      gene (tst). S. aureus (including MRSA) is an important cause of bovine mastitis,
      showing isolates with high genetic diversity and high content in virulence genes.

PMID- 29373089
TI  - Multiparametric MR Imaging of the Prostate after Treatment of Prostate Cancer.
AB  - The use of multiparametric magnetic resonance (MR) imaging in prostate cancer
      therapy is increasing, as newer treatment methods and management approaches
      emerge. The mainstays of therapy-radiation and surgery-are being supplemented
      (and even replaced) by novel focal therapy methods. Laser and ultrasonographic
      ablation, photodynamic therapy, electroporation, and cryoablation are the most
      common focal therapies, each with its own imaging findings. Typical ablation
      zones have a central focus of enhancement with peripheral rim enhancement; thus,
      dynamic contrast material-enhanced (DCE) MR imaging is the most important
      sequence for evaluation of treatment in the immediate posttherapeutic setting.
      Detection of recurrence can initiate salvage therapy, but recurrence can be
      difficult to detect on T2-weighted images, again necessitating DCE MR imaging and
      also diffusion-weighted imaging. Furthermore, the location of recurrence can vary
      depending on the therapy. With radiation therapy, the most common site of
      recurrence is the prior tumor site, whereas after prostatectomy, the recurrence
      usually occurs around the vesicoureteral anastomosis. Regarding management, there
      is an increased emphasis on watchful waiting and active surveillance, for which
      MR imaging has a critical role in both selection and follow-up of patients who
      undergo active surveillance. As MR imaging is being increasingly used for imaging
      suspected recurrence, it is important for radiologists to be familiar with the
      normal posttreatment findings and patterns and MR imaging findings of recurrence.
      (c)RSNA, 2018.

PMID- 29373092
TI  - Do Genomic Assays Provide the Necessary Confidence to De-escalate Adjuvant
      Therapy?

PMID- 29373093
TI  - Exercise Implementation in Oncology: One Size Does Not Fit All.

PMID- 29373090
TI  - The Beta 2 Adrenergic Receptor Antagonist Timolol Improves Healing of Combined
      Burn and Radiation Wounds.
AB  - In a scenario involving a nuclear detonation during war or a terrorist attack,
      acute radiation exposure combined with thermal and blast effects results in
      severe skin injury. Although the cutaneous injury in such a scenario may not be
      lethal, it may lead to inflammation, delayed wound healing and loss of the skin
      barrier, resulting in an increased risk of infection. In this study, we tested
      the potential use of timolol, a beta-adrenergic receptor antagonist, to improve
      epidermal wound closure after combined burn and radiation injury using an ex vivo
      human skin culture model. Daily application of 10 MU M timolol after combined
      injury (burn and 10 Gy ex vivo irradiation) increased wound epithelialization by
      5-20%. In addition, exposure to 10 Gy significantly suppressed epidermal
      keratinocyte proliferation by 46% at 48 h postirradiation. Similar to what has
      been observed in a thermal burn injury, the enzyme phenylethanolamine N
      methyltransferase (PNMT), which generates epinephrine, was elevated in the
      combined thermal burn and radiation wounds. This likely resulted in elevated
      tissue levels of this catecholamine, which has been shown to delay healing. Thus,
      with the addition of timolol to the wound to block the binding of locally
      generated epinephrine to the beta-adrenergic receptor, healing is improved. This
      work suggests that by antagonizing local epinephrine action within the wound, a
      beta-adrenergic receptor antagonist such as timolol may be a useful adjunctive
      treatment to improve healing in the combined burn and radiation injury.

PMID- 29373091
TI  - Validating Baboon Ex Vivo and In Vivo Radiation-Related Gene Expression with
      Corresponding Human Data.
AB  - The research for high-throughput diagnostic tests for victims of radio/nuclear
      incidents remains ongoing. In this context, we have previously identified
      candidate genes that predict risk of late-occurring hematologic acute radiation
      syndrome (HARS) in a baboon model. The goal of the current study was to validate
      these genes after radiation exposure in humans. We also examined ex vivo relative
      to in vivo measurements in both species and describe dose-response relationships.
      Eighteen baboons were irradiated in vivo to simulate different patterns of
      partial- or total-body irradiation (TBI), corresponding to an equivalent dose of
      2.5 or 5 Sv. Human in vivo blood samples were obtained from patients exposed to
      different dose ranges: diagnostic computerized tomography (CT; 0.004-0.018 Sv);
      radiotherapy for prostate cancer (0.25-0.3 Sv); and TBI of leukemia patients (2 *
      1.5 or 2 * 2 Sv, five patients each). Peripheral whole blood of another five
      baboons and human samples from five healthy donors were cultivated ex vivo and
      irradiated with 0-4 Sv. RNA was isolated pairwise before and 24 h after
      irradiation and converted into cDNA. Gene expression of six promising candidate
      genes found previously by us in a baboon model ( WNT3, POU2AF1, CCR7, ARG2,
      CD177, WLS), as well as three genes commonly used in ex vivo whole blood
      experiments ( FDXR, PCNA, DDB2) was measured using qRT-PCR. We confirmed the six
      baboon candidate genes in leukemia patients. However, expression for the
      candidate gene FDXR showed an inverse relationship, as it was downregulated in
      baboons and upregulated in human samples. Comparisons among the in vivo and ex
      vivo experiments revealed the same pattern in both species and indicated
      peripheral blood cells to represent the radiation-responsive targets causing WNT3
      and POU2AF1 gene expression changes. CCR7, ARG2, CD177 and WLS appeared to be
      altered due to radiation-responsive targets other than the whole blood cells.
      Linear dose-response relationships of FDXR, WNT3 and POU2AF1 using human ex vivo
      samples corresponded with human in vivo samples, suggesting that ex vivo models
      for in vivo dose estimates can be used over a wide dose range (0.001-5 Sv for
      POU2AF1). In summary, we validated six baboon candidate genes in humans, but the
      FDXR measurements underscored the importance of independent assessments even when
      candidates from animal models have striking gene sequence homology to humans.
      Since whole blood cells represented the same radiation-responsive targets for
      FDXR, WNT3 and POU2AF1 gene expression changes, ex vivo cell culture models can
      be utilized for in vivo dose estimates over a dose range covering up to 3.5 log
      scales. These findings might be a step forward in the development of a gene
      expression-based high-throughput diagnostic test for populations involved in
      large-scale radio/nuclear incidents.

PMID- 29373094
TI  - Phase III, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and
      Immunogenicity of SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in
      Patients Treated With Neoadjuvant Therapy for Human Epidermal Growth Factor
      Receptor 2-Positive Early Breast Cancer.
AB  - Purpose This phase III study compared SB3, a trastuzumab (TRZ) biosimilar, with
      reference TRZ in patients with human epidermal growth factor receptor 2-positive
      early breast cancer in the neoadjuvant setting ( ClinicalTrials.gov identifier:
      NCT02149524). Patients and Methods Patients were randomly assigned to receive
      neoadjuvant SB3 or TRZ for eight cycles concurrently with chemotherapy (four
      cycles of docetaxel followed by four cycles of fluorouracil, epirubicin, and
      cyclophosphamide) followed by surgery, and then 10 cycles of adjuvant SB3 or TRZ.
      The primary objective was comparison of breast pathologic complete response
      (bpCR) rate in the per-protocol set; equivalence was declared if the 95% CI of
      the ratio was within 0.785 to 1.546 or the 95% CI of the difference was within +/
      13%. Secondary end points included comparisons of total pathologic complete
      response rate, overall response rate, event-free survival, overall survival,
      safety, pharmacokinetics, and immunogenicity. Results Eight hundred patients were
      included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates
      were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR
      was 1.259 (95% CI, 1.085 to 1.460), which was within the predefined equivalence
      margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the
      lower limit contained within and the upper limit outside the equivalence margin.
      The total pathologic complete response rates were 45.8% and 35.8% and the overall
      response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Overall,
      96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and
      10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up
      to cycle 9) with SB3 and TRZ, respectively. Conclusion Equivalence for efficacy
      was demonstrated between SB3 and TRZ on the basis of the ratio of bpCR rates.
      Safety and immunogenicity were comparable.

PMID- 29373095
TI  - Reply to S.C. Adams et al, C. Lopez et al, and R.U. Newton et al.

PMID- 29373096
TI  - What Is the "Home" in Home-Based Exercise? The Need to Define Independent
      Exercise for Survivors of Cancer.

PMID- 29373097
TI  - Effective Exercise Interventions for Patients and Survivors of Cancer Should be
      Supervised, Targeted, and Prescribed With Referrals From Oncologists and General
      Physicians.

PMID- 29373098
TI  - Reply to M. Horiguchi et al.

PMID- 29373099
TI  - Evaluating Noninferiority With Clinically Interpretable Statistics for the
      PROSELICA Study to Assess Treatment Efficacy of a Reduced Dose of Cabazitaxel for
      Treating Metastatic Prostate Cancer.

PMID- 29373101
TI  - There seems to be no benefit from using bioactive proteins in bone-augmentation
      procedures for implant placement.

PMID- 29373102
TI  - Tranexamic acid may result in small decrease in blood loss in patients undergoing
      orthognathic surgery.

PMID- 29373103
TI  - Insufficient evidence about the association between primary tooth eruption and
      fever.

PMID- 29373100
TI  - Impact of EML4-ALK Variant on Resistance Mechanisms and Clinical Outcomes in ALK
      Positive Lung Cancer.
AB  - Purpose Advanced anaplastic lymphoma kinase ( ALK) fusion-positive non-small-cell
      lung cancers (NSCLCs) are effectively treated with ALK tyrosine kinase inhibitors
      (TKIs). However, clinical outcomes in these patients vary, and the benefit of
      TKIs is limited as a result of acquired resistance. Emerging data suggest that
      the ALK fusion variant may affect clinical outcome, but the molecular basis for
      this association is unknown. Patients and Methods We identified 129 patients with
      ALK-positive NSCLC with known ALK variants. ALK resistance mutations and clinical
      outcomes on ALK TKIs were retrospectively evaluated according to ALK variant. A
      Foundation Medicine data set of 577 patients with ALK-positive NSCLC was also
      examined. Results The most frequent ALK variants were EML4-ALK variant 1 in 55
      patients (43%) and variant 3 in 51 patients (40%). We analyzed 77 tumor biopsy
      specimens from patients with variants 1 and 3 who had progressed on an ALK TKI.
      ALK resistance mutations were significantly more common in variant 3 than in
      variant 1 (57% v 30%; P = .023). In particular, ALK G1202R was more common in
      variant 3 than in variant 1 (32% v 0%; P < .001). Analysis of the Foundation
      Medicine database revealed similar associations of variant 3 with ALK resistance
      mutation and with G1202R ( P = .010 and .015, respectively). Among patients
      treated with the third-generation ALK TKI lorlatinib, variant 3 was associated
      with a significantly longer progression-free survival than variant 1 (hazard
      ratio, 0.31; 95% CI, 0.12 to 0.79; P = .011). Conclusion Specific ALK variants
      may be associated with the development of ALK resistance mutations, particularly
      G1202R, and provide a molecular link between variant and clinical outcome. ALK
      variant thus represents a potentially important factor in the selection of next
      generation ALK inhibitors.

PMID- 29373104
TI  - Continuous positive airway pressure probably results in fewer apnea-hypopnea
      episodes per hour but not in less sleepiness compared with mandibular advance
      devices in patients with obstructive sleep apnea.

PMID- 29373105
TI  - Meta-Analysis Comparing the Safety and Efficacy of Dual Versus Triple
      Antithrombotic Therapy in Patients With Atrial Fibrillation Undergoing
      Percutaneous Coronary Intervention.
AB  - In patients with atrial fibrillation undergoing percutaneous coronary
      intervention (PCI), the effectiveness and safety of dual compared with triple
      antithrombotic therapy are a matter of debate, especially when considering the
      prevention of end points at low incidence, such as myocardial infarction (MI),
      stent thrombosis, or mortality. This study-level meta-analysis included 4
      controlled randomized trials and 6,036 patients with a clinical indication to
      chronic oral anticoagulation (OAC) after PCI, mainly for atrial fibrillation.
      Patients receiving dual therapy with a single antiplatelet agent, essentially a
      P2Y12 inhibitor, plus OAC were compared with those treated with triple therapy
      (aspirin, a P2Y12 inhibitor, and OAC). The incidence of the following outcomes
      was evaluated: Thrombolysis In Myocardial Infarction major and minor bleeding,
      MI, stent thrombosis, stroke, cardiovascular, and all-cause death. Occurrence of
      Thrombolysis In Myocardial Infarction major bleeding was significantly lower in
      patients treated with dual therapy: 1.97% versus 3.53% in those on triple therapy
      (odds ratios 0.55, 95% confidence interval 0.39 to 0.78, p = 0.0007); rates of
      minor bleeding were also decreased in the former (57% relative reduction). With
      dual therapy, there was not a statistically significant difference in all-cause
      and cardiovascular mortality (3.81% vs 4.01%, p = 0.37 and 1.62% vs 2.02%, p =
      0.42, respectively). Incidence of MI (3.25% vs 2.78%, p = 0.61), definite stent
      thrombosis (0.92% vs 0.66%, p = 0.46), and stroke (1.28% vs 1.32%, p = 0.85) was
      similar in the 2 treatment strategies. In patients with long-term indication to
      OAC after PCI, compared with triple therapy, dual antithrombotic therapy reduces
      bleeding, without an excess in thromboembolic and ischemic cardiac events.

PMID- 29373107
TI  - Letter to the Editor.

PMID- 29373106
TI  - [Papillomavirus, could we speak about cancer and prevention?]

PMID- 29373109
TI  - Recurrent Facial Edema.

PMID- 29373108
TI  - Blood lead levels and longitudinal language outcomes in children from 4 to 12
      years.
AB  - OBJECTIVES: In this study, the authors aimed to examine the association of a
      range of blood lead levels on language skills assessed at 4, 6, 10 and 12 years
      of age using a prospective longitudinal design controlling for potential
      confounding variables including maternal vocabulary, caregiver's psychological
      distress and symptomatology, child's race and prenatal drug exposure. METHODS:
      The participants (N = 278) were a subsample of a large longitudinal study that
      examined the association of prenatal drug exposure on children who were followed
      prospectively from birth and assessed for receptive and expressive language
      skills at 4, 6, 10 and 12 years of age. Blood lead levels were determined at 4
      years of age by atomic absorption spectrometry. A mixed model approach with
      restricted maximum likelihood procedures was used to assess the association of
      lead on language outcomes. RESULTS: Longitudinal mixed model analyses suggested a
      negative effect of lead exposure on both receptive and expressive language, with
      the adverse outcomes of lead exposure appearing to become more prominent at 10
      and 12 years. Higher caregiver vocabulary was positively associated with child's
      language scores whereas caregiver psychological distress appeared to negatively
      affect language scores. Prenatal drug exposure was not related to the effects of
      lead on language skills. CONCLUSIONS: These findings suggest that elevated blood
      lead levels occurring early in life may be associated with poorer language skills
      at older ages. A language rich environment may minimize the negative influence of
      early lead exposure on language skills, with psychological distress seemingly
      exacerbating the negative outcome.

PMID- 29373110
TI  - Gorlin Syndrome.
AB  - Gorlin syndrome is a rare autosomal dominant disease caused by mutations in the
      sonic hedgehog signaling pathway. Of particular importance is the PTCH1 gene. The
      disease is characterized by the development of multiple basal cell carcinomas at
      young ages. These tumors may present with other skin manifestations such as
      palmoplantar pits and with extracutaneous manifestations such as odontogenic
      keratocysts and medulloblastoma. Although the dermatologist may be key for
      recognizing clinical suspicion of the syndrome, a multidisciplinary team is
      usually necessary for diagnosis, treatment, and follow-up. Skin treatment may be
      complicated due to the large number of basal cell carcinomas and the extent of
      involvement. In recent years, new drugs that inhibit targets in the sonic
      hedgehog pathway have been developed. Although these agents appear promising
      options for patients with Gorlin syndrome, their efficacy is limited by adverse
      effects and the development of resistance.

PMID- 29373112
TI  - Ergonomics in Dermatology: Good Posture During Physical Examinations.

PMID- 29373111
TI  - Description of patients excluded for Mohs surgery after pre-surgical evaluation:
      data from the Regesmohs Spanish registry.
AB  - BACKGROUND: Regesmohs registry is a nationwide registry including patients
      evaluated for Mohs surgery in 17 Spanish centres since July 2013. Given that Mohs
      surgery is the therapy with best results for high risk basal cell carcinoma (BCC)
      and other skin tumours, we wanted to describe the reasons that lead to some
      patients being excluded from this therapy and the alternative treatments that
      they received. These data may be useful to avoid excluding patients for Mohs
      surgery use, to estimate the healthcare demand of these patients and the demand
      for Hedgehog inhibitors therapy in this group. OBJECTIVE: To describe patients
      excluded for Mohs surgery after pre-surgical assessment, and the treatments that
      they received. METHODS: Regesmohs includes all consecutive patients assessed for
      Mohs surgery in the participating centres, collecting data on patient
      characteristics, intervention, and short and long-term results. Patients excluded
      for Mohs surgery after pre-surgical evaluation were described. RESULTS: 3011
      patients were included in Regesmohs from July 2013 to October 2016. In 85, Mohs
      surgery was not performed as they were considered inadequate candidates. 67 had
      BCC. Reasons for exclusion were: medical contraindication (27.1%, n=23) low-risk
      tumour in (18.8%, n=16) and giant tumour and bone invasion (15.3%, n=13). Only 1
      patient (1.2%) showed lymph node involvement and no patients had visceral
      metastases. Of the 85 excluded patients, 29 (34.1%) were treated with
      conventional surgery, 24 (28.3%) with radiotherapy, 4 (4.7%) with inhibitors of
      the Hedgehog pathway (only indicated for BCC), and 2 (2.4%) received palliative
      care. We had no follow-up data on 14 patients (16.5%). CONCLUSION: Medical
      comorbidities were the most common reason for withholding Mohs surgery.
      Withholding therapy on the basis of distant extension is uncommon. Most excluded
      patients received simpler therapies: conventional surgery or radiotherapy, with
      hedgehog inhibitors being a new option.

PMID- 29373113
TI  - Comparison of the effects of 1MHz and 3MHz therapeutic ultrasound on endothelium
      dependent vasodilation of humans: a randomised clinical trial.
AB  - OBJECTIVE: To compare the effects of different waveforms of 1MHz and 3MHz
      therapeutic ultrasound on endothelial function in healthy subjects. DESIGN:
      Randomised placebo-controlled, crossover study with concealed allocation and
      assessor blinding. SETTING: Imaging Centre of the University Hospital.
      PARTICIPANTS: Thirty volunteers aged between 18 and 35 years were divided into
      two homogeneous groups (1MHz and 3MHz). INTERVENTIONS: Continuous (CUT;
      0.4W/cm2SATA), pulsed (PUT; 20% duty cycle, 0.08W/cm2SATA) and placebo waveforms
      (equipment off) of ultrasound (1MHz and 3MHz) were randomized and applied over
      the brachial artery for 5minutes. MAIN OUTCOME MEASURES: Endothelial function was
      evaluated using the flow-mediated dilation (FMD) technique. RESULTS: Both 1MHz
      [CUT: mean difference 4%, 95% confidence interval (CI) 2 to 6%, P<0.001; PUT:
      mean difference 4%, 95% CI 2 to 6%, P<0.001] and 3MHz (CUT: mean difference 4%,
      95% CI 2 to 6%, P<0.001; PUT: mean difference 4%, 95% CI 2 to 6%, P<0.001) of
      therapeutic ultrasound increased %FMD by approximately 4% compared with the
      placebo waveforms. The endothelium-dependent vasodilator responses were the same
      for both types of waves and frequencies. No differences in baseline diameter,
      hyperaemic flow, and nitroglycerin-mediated diameter and vasodilation were
      observed between groups. CONCLUSION: Both CUT and PUT ultrasound waveforms
      improved endothelial function. The 1MHz and 3MHz frequencies of therapeutic
      ultrasound led to similar improvement in endothelial function in healthy
      volunteers. Clinical trial registration number RBR-4z5z3t.

PMID- 29373114
TI  - The influence of pre-existing rib fractures on Global Human Body Models
      Consortium thorax response in frontal and oblique impact.
AB  - Many post-mortem human subjects (PMHS) considered for use in biomechanical impact
      tests have pre-existing rib fractures (PERFs), usually resulting from
      cardiopulmonary resuscitation. These specimens are typically excluded from impact
      studies with the assumption that the fractures will alter the thoracic response
      to loading. We previously used the Global Human Body Models Consortium 50th
      percentile whole-body finite element model (GHBMC M50-O) to demonstrate that up
      to three lateral or bilateral PERFs do not meaningfully influence the response of
      the GHBMC thorax to lateral loading. This current study used the GHBMC M50-O to
      explore the influence of PERFs on thorax response in frontal and oblique loading.
      Up to six PERFs were simulated on the anterior or lateral rib regions, and the
      model was subjected to frontal or oblique cylindrical impactor, frontal seatbelt,
      or frontal seatbelt + airbag loading. Changes in thorax force-compression
      responses due to PERFs were generally minor, with the greatest alterations seen
      in models with six PERFs on one side of the ribcage. The observed changes,
      however, were small relative to mid-size male corridors for the loading
      conditions simulated. PERFs altered rib strain patterns, but the changes did not
      translate to changes in global thoracic response. Within the limits of model
      fidelity, the results suggest that PMHS with up to six PERFs may be appropriate
      for use in frontal or oblique impact testing.

PMID- 29373115
TI  - Active disturbance rejection control based robust output feedback autopilot
      design for airbreathing hypersonic vehicles.
AB  - Since motion control plant (y(n)=f(?)+d) was repeatedly used to exemplify how
      active disturbance rejection control (ADRC) works when it was proposed, the
      integral chain system subject to matched disturbances is always regarded as a
      canonical form and even misconstrued as the only form that ADRC is applicable to.
      In this paper, a systematic approach is first presented to apply ADRC to a
      generic nonlinear uncertain system with mismatched disturbances and a robust
      output feedback autopilot for an airbreathing hypersonic vehicle (AHV) is devised
      based on that. The key idea is to employ the feedback linearization (FL) and
      equivalent input disturbance (EID) technique to decouple nonlinear uncertain
      system into several subsystems in canonical form, thus it would be much easy to
      directly design classical/improved linear/nonlinear ADRC controller for each
      subsystem. It is noticed that all disturbances are taken into account when
      implementing FL rather than just omitting that in previous research, which
      greatly enhances controllers' robustness against external disturbances. For
      autopilot design, ADRC strategy enables precise tracking for velocity and
      altitude reference command in the presence of severe parametric perturbations and
      atmospheric disturbances only using measurable output information. Bounded-input
      bounded-output (BIBO) stable is analyzed for closed-loop system. To illustrate
      the feasibility and superiority of this novel design, a series of comparative
      simulations with some prominent and representative methods are carried out on a
      benchmark longitudinal AHV model.

PMID- 29373116
TI  - Uncommon hereditary gynaecological tumour syndromes: pathological features in
      tumours that may predict risk for a germline mutation.
AB  - The most common hereditary gynaecological tumour syndromes are hereditary breast
      and ovarian cancer syndrome and Lynch syndrome. However, pathologists also may
      encounter gynaecological tumours in women with rare hereditary syndromes. Many of
      these tumours exhibit distinctive gross and microscopic features that are
      associated with a risk for an inherited gene mutation. The sensitivity and
      specificity of these tumour pathology features for predicting an inherited
      mutation vary depending on the syndrome. By recognising these tumour features,
      pathologists may potentially contribute to the diagnosis of an unsuspected
      syndrome by recommending referral of the patient for formal risk assessment by
      genetic counselling. Patients additionally benefit from diagnosis of an inherited
      syndrome because many also carry a lifetime risk for developing primary
      malignancies outside of the gynaecological tract. Early diagnosis of an inherited
      syndrome permits early screening, detection, and management of additional
      malignancies associated with the syndrome. This review highlights these rare
      syndromes and their tumour pathology, including Peutz-Jeghers syndrome (gastric
      type mucinous carcinoma of the cervix; ovarian sex cord tumour with annular
      tubules); hereditary leiomyoma renal cell carcinoma syndrome (uterine leiomyoma);
      tuberous sclerosis complex (uterine PEComa; uterine lymphangioleiomyomatosis);
      DICER1 syndrome (ovarian Sertoli-Leydig cell tumour; cervical embryonal
      rhabdomyosarcoma); rhabdoid tumour predisposition syndrome 2 (small cell
      carcinoma of the ovary, hypercalcaemic type); Cowden syndrome (endometrial
      endometrioid adenocarcinoma); naevoid basal cell carcinoma syndrome (ovarian
      fibroma); and Von Hippel-Lindau syndrome (clear cell papillary cystadenoma of the
      broad ligament).

PMID- 29373118
TI  - Prognostic implications of telomerase expression in pituitary adenomas.
AB  - OBJECTIVES: To analyse the prognostic value of telomerase expression in patients
      with pituitary adenomas (PAs) followed-up for at least 8 years. PATIENTS AND
      METHODS: A retrospective study was conducted of samples from 51 PAs (40 typical
      and 11 atypical) from patients who underwent transsphenoidal surgery between 2006
      and 2008 and from 10 normal pituitary glands obtained by autopsy. Telomerase
      expression was assessed by immunohistochemistry, correlating the expression with
      that of Ki-67 and p53. RESULTS: We observed telomerase expression in 43 PAs
      (84.3%, 32 of the 40 typical PAs and in the 11 atypical PAs), which was higher in
      the clinically nonfunctioning cases (P=.0034) and very rare in the patients with
      acromegaly (P=.0001). There was a significant association between the percentage
      of tumour cells (>10%) and the recurrence of the adenoma (P=.039). There was no
      correlation with the expression of Ki-67 and p53 (P=.4986), and there were no
      differences according to age, sex, tumour size and invasiveness. CONCLUSIONS: A
      telomerase expression rate greater than 10% in the pituitary tumour tissue was
      associated with recurrence or progression of the PA, especially in the
      nonfunctioning cases.

PMID- 29373117
TI  - The evolution of cognitive models: From neuropsychology to neuroimaging and back.
AB  - This paper provides a historical and future perspective on how neuropsychology
      and neuroimaging can be used to develop cognitive models of human brain
      functions. Section 1 focuses on the emergence of cognitive modelling from
      neuropsychology, why lesion location was considered to be unimportant and the
      challenges faced when mapping symptoms to impaired cognitive processes. Section 2
      describes how established cognitive models based on behavioural data alone cannot
      explain the complex patterns of distributed brain activity that are observed in
      functional neuroimaging studies. This has led to proposals for new cognitive
      processes, new cognitive strategies and new functional ontologies for cognition.
      Section 3 considers how the integration of data from lesion, behavioural and
      functional neuroimaging studies of large cohorts of brain damaged patients can be
      used to determine whether inter-patient variability in behaviour is due to
      differences in the premorbid function of each brain region, lesion site or
      cognitive strategy. This combination of neuroimaging and neuropsychology is
      providing a deeper understanding of how cognitive functions can be lost and re
      learnt after brain damage - an understanding that will transform our ability to
      generate and validate cognitive models that are both physiologically plausible
      and clinically useful.

PMID- 29373119
TI  - Nuclear Excluded Autism-Associated Phosphatase and Tensin Homolog Mutations
      Dysregulate Neuronal Growth.
AB  - BACKGROUND: Phosphatase and tensin homolog (PTEN) negatively regulates downstream
      protein kinase B signaling, resulting in decreased cellular growth and
      proliferation. PTEN is mutated in a subset of children with autism spectrum
      disorder (ASD); however, the mechanism by which specific point mutations alter
      PTEN function is largely unknown. Here, we assessed how ASD-associated single
      nucleotide variations in PTEN (ASD-PTEN) affect function. METHODS: We used viral
      mediated molecular substitution of human PTEN into Pten knockout mouse neurons
      and assessed neuronal morphology to determine the functional impact of ASD-PTEN.
      We employed molecular cloning to examine how PTEN's stability, subcellular
      localization, and catalytic activity affect neuronal growth. RESULTS: We
      identified a set of ASD-PTEN mutations displaying altered lipid phosphatase
      function and subcellular localization. We demonstrated that wild-type PTEN can
      rescue the neuronal hypertrophy, while PTEN H93R, F241S, D252G, W274L, N276S, and
      D326N failed to rescue this hypertrophy. A subset of these mutations lacked
      nuclear localization, prompting us to examine the role of nuclear PTEN in
      regulating neuronal growth. We found that nuclear PTEN alone is sufficient to
      regulate soma size. Furthermore, forced localization of the D252G and W274L
      mutations into the nucleus partially restores regulation of soma size.
      CONCLUSIONS: ASD-PTEN mutations display decreased stability, catalytic activity,
      and/or altered subcellular localization. Mutations lacking nuclear localization
      uncover a novel mechanism whereby lipid phosphatase activity in the nucleus can
      regulate mammalian target of rapamycin signaling and neuronal growth.

PMID- 29373122
TI  - WITHDRAWN: Non-infectious stressors and innate immune response.
AB  - This article has been withdrawn at the request of the author(s). The Publisher
      apologizes for any inconvenience this may cause. The full Elsevier Policy on
      Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 29373121
TI  - Thalamic Control of Cognition and Social Behavior Via Regulation of Gamma
      Aminobutyric Acidergic Signaling and Excitation/Inhibition Balance in the Medial
      Prefrontal Cortex.
AB  - BACKGROUND: The mediodorsal thalamus plays a critical role in cognition through
      its extensive innervation of the medial prefrontal cortex (mPFC), but how the two
      structures cooperate at the single-cell level to generate associated cognitive
      functions and other mPFC-dependent behaviors remains elusive. Maintaining the
      proper balance between excitation and inhibition (E/I balance) is of principal
      importance for organizing cortical activity. Furthermore, the PFC E/I balance has
      been implicated in successful execution of multiple PFC-dependent behaviors in
      both animal research and the context of human psychiatric disorders. METHODS:
      Here, we used a pharmacogenetic strategy to decrease mediodorsal thalamic
      activity in adult male rats and evaluated the consequences for E/I balance in PFC
      pyramidal neurons as well as cognition, social interaction, and anxiety. RESULTS:
      We found that dampening mediodorsal thalamic activity caused significant
      reductions in gamma-aminobutyric acidergic signaling and increased E/I balance in
      the mPFC and was concomitant with abnormalities in these behaviors. Furthermore,
      by selectively activating parvalbumin interneurons in the mPFC with a novel
      pharmacogenetic approach, we restored gamma-aminobutyric acidergic signaling and
      E/I balance as well as ameliorated all behavioral impairments. CONCLUSIONS: These
      findings underscore the importance of thalamocortical activation of mPFC gamma
      aminobutyric acidergic interneurons in a broad range of mPFC-dependent behaviors.
      Furthermore, they highlight this circuitry as a platform for therapeutic
      investigation in psychiatric diseases that involve impairments in PFC-dependent
      behaviors.

PMID- 29373123
TI  - FOREWORD.

PMID- 29373120
TI  - Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents.
AB  - Sleep homeostasis and circadian function are important maintaining factors for
      optimal health and well-being. Conversely, sleep and circadian disruptions are
      implicated in a variety of adverse health outcomes, including substance use
      disorders. These risks are particularly salient during adolescence. Adolescents
      require 8 to 10 hours of sleep per night, although few consistently achieve these
      durations. A mismatch between developmental changes and social/environmental
      demands contributes to inadequate sleep. Homeostatic sleep drive takes longer to
      build, circadian rhythms naturally become delayed, and sensitivity to the phase
      shifting effects of light increases, all of which lead to an evening preference
      (i.e., chronotype) during adolescence. In addition, school start times are often
      earlier in adolescence and the use of electronic devices at night increases,
      leading to disrupted sleep and circadian misalignment (i.e., social jet lag).
      Social factors (e.g., peer influence) and school demands further impact sleep and
      circadian rhythms. To cope with sleepiness, many teens regularly consume highly
      caffeinated energy drinks and other stimulants, creating further disruptions in
      sleep. Chronic sleep loss and circadian misalignment enhance developmental
      tendencies toward increased reward sensitivity and impulsivity, increasing the
      likelihood of engaging in risky behaviors and exacerbating the vulnerability to
      substance use and substance use disorders. We review the neurobiology of brain
      reward systems and the impact of sleep and circadian rhythms changes on addiction
      vulnerability in adolescence and suggest areas that warrant additional research.

PMID- 29373124
TI  - Binding kinetics of five drugs to beta2-adrenoceptor using peak profiling method
      and nonlinear chromatography.
AB  - Investigations of drug-protein interactions have advanced our knowledge of ways
      to design more rational drugs. In addition to extensive thermodynamic studies,
      ongoing works are needed to enhance the exploration of drug-protein binding
      kinetics. In this work, the beta2-adrenoceptor (beta2-AR) was immobilized on N,
      N'-carbonyldiimidazole activated amino polystyrene microspheres to prepare an
      affinity column (4.6 mm * 5.0 cm, 8 MUm). The beta2-AR column was utilized to
      determine the binding kinetics of five drugs to the receptor. Introducing peak
      profiling method into this receptor chromatographic analysis, we determined the
      dissociation rate constants (kd) of salbutamol, terbutaline, methoxyphenamine,
      isoprenaline hydrochloride and ephedrine hydrochloride to beta2-AR to be 15 (+/
      1), 22 (+/-1), 3.3 (+/-0.2), 2.3 (+/-0.2) and 2.1 (+/-0.1) s-1, respectively. The
      employment of nonlinear chromatography (NLC) in this case exhibited the same rank
      order of kd values for the five drugs bound to beta2-AR. We confirmed that both
      the peak profiling method and NLC were capable of routine measurement of receptor
      drug binding kinetics. Compared with the peak profiling method, NLC was
      advantageous in the simultaneous assessment of the kinetic and apparent
      thermodynamic parameters. It will become a powerful method for high throughput
      drug-receptor interaction analysis.

PMID- 29373126
TI  - Scalability of pre-packed preparative chromatography columns with different
      diameters and lengths taking into account extra column effects.
AB  - Small pre-packed columns are commonly used to estimate the optimum run parameters
      for pilot and production scale. The question arises if the experiments obtained
      with these columns are scalable, because there are substantial changes in extra
      column volume when going from a very small scale to a benchtop column. In this
      study we demonstrate the scalability of pre-packed disposable and non-disposable
      columns of volumes in the range of 0.2-20 ml packed with various media using
      superficial velocities in the range of 30-500 cm/h. We found that the relative
      contribution of extra column band broadening to total band broadening was not
      only high for columns with small diameters, but also for columns with a larger
      volume due to their wider diameter. The extra column band broadening can be more
      than 50% for columns with volumes larger than 10 ml. An increase in column
      diameter leads to high additional extra column band broadening in the filter,
      frits, and adapters of the columns. We found a linear relationship between intra
      column band broadening and column length, which increased stepwise with increases
      in column diameter. This effect was also corroborated by CFD simulation. The
      intra column band broadening was the same for columns packed with different
      media. An empirical engineering equation and the data gained from the extra
      column effects allowed us to predict the intra, extra, and total column band
      broadening just from column length, diameter, and flow rate.

PMID- 29373125
TI  - Highly uniform porous silica layer open-tubular capillary columns produced via in
      situ biphasic sol-Gel processing for open-tubular capillary
      electrochromatography.
AB  - We report a highly uniform porous layer open tubular (PLOT) column for capillary
      electrochromatography (CEC) analysis. The PLOT column is easily fabricated using
      a single-step in-situ biphasic reaction, producing homogeneous porous-layer
      modified surface with ~240 nm thickness in a 50 MUm-id capillary. CEC performance
      of the PLOT column has been investigated and optimized under various experimental
      parameters. Using a mixture of naphthalene and biphenyl as the test sample, we
      show that the PLOT column exhibits good separation efficiency with resolution
      >3.0 and theoretical plate numbers over 6 * 104, as well as good intra-/inter-day
      repeatability and column-to-column repeatability. The column has been
      successfully applied for CEC analysis of three different types of samples without
      any further modification of the columns, including complicated peptide products
      from tryptic-digestion of proteins (lysozyme and BSA), beta-blockers (basic
      samples) and polycyclic aromatic hydrocarbons (neutral samples). Efficient
      separation has been achieved, which could be attributed to the enhanced surface
      to-volume ratio of the PLOT column that will increase the interaction between
      solid phase and mobile phase in CEC. In addition, base-line separation of neutral
      samples indicates the reversed phase chromatographic property of the PLOT column,
      which could be induced by the residue of hexadecyltrimethylammonium bromide used
      in the fabrication process. Our study show that the present PLOT column is a
      promising approach that can significantly enhance CEC separation efficiency and
      could be of potential value in analysis of various different samples.

PMID- 29373127
TI  - Microwave-assisted decomplexation and in-situ headspace in-syringe dynamic
      derivatization of dimethylamine borane with high performance liquid
      chromatography-fluorescence detection.
AB  - A rapid, sensitive, selective, and simple method for monitoring dimethylamine
      borane (DMAB) in aqueous sample is proposed by combining microwave-assisted de
      complexation, headspace liquid phase in-situ derivatization extraction, and high
      performance liquid chromatography-fluorescence detection for the determination of
      DMAB in samples. The present procedure involves de-complexation of DMAB using
      microwave irradiation, evolution of dimethylamine (DMA) to the headspace from an
      alkalized sample solution, and dynamic headspace liquid-phase derivatization
      extraction (Dy-HS-LPDE) of DMA with 9-fluorenylmethyl chloroformate in a syringe
      barrel. In addition to the optimal Dy-HS-LPDE and chromatographic parameters
      described in our previous study, the de-complexation of DMAB by thermal and
      microwave-assisted procedures and evolution of DMA into the headspace from an
      alkalized solution and modification of the Dy-HS-LPDE method are thoroughly
      investigated. The results indicate that complete de-complexation was obtained at
      70  degrees C for 5 min, 30  degrees C for 10 min, or using microwave irradiation
      for 30 s at any applied power. It indicates that the DMAB complex easily
      undergoes de-complexation under microwave irradiation. The linearity range was
      0.01-0.5 mg L-1 for DMAB and 0.0077-0.38 mg L-1 for DMA, with a coefficient of
      determination of 0.9995, and limit of detection of 3 MUg L-1 (limit of
      quantitation of 10 MUg L-1) for DMAB. The recoveries of DMAB are 95.3% (3.0% RSD)
      for waste water when spiked 0.05 mg L-1 and 93.5% (5.4% RSD) for the samples
      spiked with copper and nickel salts (5 mM each in the spiked waste sample). The
      whole analytical procedure can be completed within 25 min. The results confirm
      that the present method is a rapid, sensitive, selective, automated, low-cost and
      eco-friendly procedure to identify DMAB in samples.

PMID- 29373128
TI  - Early stages in the history of gas chromatography.
AB  - The creation of gas chromatography is traditionally associated with the names of
      Nobel Prize winner Archer Martin and his colleagues Richard Synge and Anthony
      James. However, sometimes references to their predecessors can be found. An
      investigation conducted by the authors of this article not only confirmed the
      reliability of these references; but in fact led to the conclusion that by 1952,
      which is commonly believed to be the year when gas chromatography was born, many
      research papers had already been devoted to this method, mainly, in its gas-solid
      version. These papers are considered in this article.

PMID- 29373129
TI  - Profiling of polyunsaturated fatty acids in human serum using off-line and on
      line solid phase extraction-nano-liquid chromatography-quadrupole-time-of-flight
      mass spectrometry.
AB  - Polyunsaturated fatty acids (PUFAs) play a pivotal role in the biological
      effects, and are the potential biomarkers for some diseases. However, the
      structural diversity and similarity, the low concentration, and the interference
      of high abundant endogenous components challenge the PUFAs profiling. Herein, a
      novel analytical approach, off-line and on-line solid phase extraction-nano
      liquid chromatography-quadrupole-time-of-flight mass spectrometry (off-line and
      on-line SPE-nano-LC-Q-TOF-MS), was established to monitor the PUFAs. The
      combination of off-line and on-line SPE removed most of impurities, and the
      recoveries ranged from 80.1% to 93.0% and the matrix effects were from 85.1% to
      92.8%. Using this method, 51 PUFAs could be separated well and quantified with
      the limits of quantification between 0.006 and 2.2 pg. Finally, this developed
      method was applied successfully to simultaneously qualify and quantify the
      potential biomarkers in the allergic patients. 21 PUFAs including LTB4, 5S-, 11S
      , 15S-HETE and 15S-HEPE showed significant differences. Our study indicated that
      the established method has the potential to sensitively and accurately determine
      the PUFAs in biological samples.

PMID- 29373130
TI  - Hypersensitivity to levothyroxine: A case report of a successful oral
      desensitization.

PMID- 29373132
TI  - In situ analysis of gelatinolytic activity in human dentin.
AB  - Matrix metalloproteinases (MMPs) such as gelatinases are differentially expressed
      in human tissues. These enzymes cleave specific substrates involved in cell
      signaling, tissue development and remodeling and tissue breakdown. Recent
      evidences show that gelatinases are crucial for normal dentin development and
      their activity is maintained throughout the entire tooth function in the oral
      cavity. Due to the lack of information about the exact location and activity of
      gelatinases in mature human dentin, the present study was designed to examine
      gelatinolytic levels in sound dentin. In situ zymography using confocal
      microscopy was performed on both mineralized and demineralized dentin samples.
      Sites presenting gelatinase activity were identified throughout the entire
      biological tissue pursuing different gelatinolytic levels for distinct areas:
      predentin and dentinal tubule regions presented higher gelatinolytic activity
      compared to intertubular dentin. Dentin regions with higher gelatinolytic
      activity immunohistochemically were partially correlated with MMP-2 expression.
      The maintenance of gelatinolytic activity in mature dentin may have biological
      implications related to biomineralization of predentin and tubular/peritubular
      dentinal regions, as well as regulation of defensive mechanisms of the dentin
      pulp complex.

PMID- 29373131
TI  - [Rheumatoid arthritis and polycythemia vera JAK2 negative association:
      Polycythemia may be worsening under methotrexate?]

PMID- 29373133
TI  - Genotoxic and mutagenic potential of camphorquinone in L5178/TK+/- mouse lymphoma
      cells.
AB  - OBJECTIVES: Camphorquinone (CQ) is the most important photoinitiator used in
      dental composite resins. Sparse data indicate a mutagenic potential of CQ.
      Therefore, it was aim of this study to evaluate the cytotoxicity, genotoxicity,
      and mutagenicity of CQ in L5178Y TK+/- mouse lymphoma cells. METHODS: L5178Y/TK+/
      cells were exposed to different concentrations of non-irradiated CQ (0.25
      2.5mM). Cytotoxicity was evaluated by propidium iodide assay, determination of
      suspension growth rate, relative total growth and the mitotic index.
      Intracellular levels of reactive oxygen/nitrogen species (ROS/RNS) were
      quantified by 2',7'-dichlorofluoresceine diacetate (DCFH-DA). Early induction of
      DNA strand breaks and oxidative DNA base lesions was assessed using the 8
      hydroxyguanine DNA-glycosylase 1 (hOGG1)-modified alkaline comet assay, whereas
      mutagenicity of CQ was determined in the mouse lymphoma TK assay (MLA), according
      to OECD Guideline No. 490. RESULTS: CQ (0.5-2.5mM) induced concentration- and
      time-dependent inhibition of cell growth associated with increased ROS/RNS
      production, amounting to 2342%+/-1108% of controls after 90min at 2.5mM.
      Additionally, CQ concentration-dependently caused direct DNA-damage, i.e.
      formation of DNA strand breaks and 8-hydroxy-2'-deoxyguanosine. Whereas the MLA
      indicated lack of mutagenicity of CQ after a 4h of treatment, CQ concentration
      dependently increased total mutant frequency (MF) after 24h (about 2-fold at
      2.5mM). But, based on the global evaluation factor concept, increase in MF did
      not reach biologically relevance. SIGNIFICANCE: CQ induced concentration
      dependent, cytotoxic and genotoxic effects in L5178Y/TK+/- cells, most likely due
      to oxidative stress, but without mediating obvious biological relevant
      mutagenicity.

PMID- 29373134
TI  - Wear of polyetherketoneketones - Influence of titanium dioxide content and
      antagonistic material.
AB  - OBJECTIVE: The aim of this laboratory study was to analyze the influence of
      titanium dioxide (TiO2) content and antagonistic material on the wear of
      polyetherketoneketones (PEKKs). METHODS: Twenty-four disk-shaped specimens of two
      PEKK materials containing either 10wt% or 20wt% TiO2 particles (P10 and P20) were
      dynamically loaded in a chewing simulator with 49N and additional thermal cycling
      (5-55 degrees C). Subgroups of 8 specimens each were loaded with spherical
      antagonists made from either steatite ceramic (St), zirconia (Zr), or the same
      PEKK material (P10 or P20). After 120,000, 240,000, 480,000, 840,000, and
      1,200,000 loading cycles the vertical substance loss and the volume loss of the
      loaded specimens were evaluated using a laser scanner. Data were checked
      considering the normal distribution (Shapiro-Wilk test) and were inspected for
      significant differences by means of single factor variance analyses and post hoc
      pair comparison (Games-Howell test). RESULTS: After 1,200,000 chewing cycles,
      statistical analyses revealed a significant influence of the antagonistic
      material. A significant difference was also found between the tested PEKKs if Zr
      was used as the antagonist. The volume loss ranged from between 0.073mm3 (P20
      P20) and 0.228mm3 (P10-St), and the vertical substance loss ranged between
      73.71MUm (P20-P20) and 115.268MUm (P10-Zr). SIGNIFICANCE: The inclusion of TiO2
      particles influences the wear behavior of PEKK materials.

PMID- 29373135
TI  - PAFIYAMA syndrome evidence in highly trained population.

PMID- 29373136
TI  - Impact of a novel contrast reduction system on contrast savings in coronary
      angiography - The DyeVert randomised controlled trial.
AB  - AIMS: The most prominent procedure-related and thus modifiable risk factor for
      contrast-induced acute kidney injury is contrast media (CM) volume. The DyeVertTM
      system has been designed to reduce the amount of CM. The primary objective of
      this randomised controlled trial was thus to examine whether the novel DyeVertTM
      contrast reduction system (Osprey Medical Inc., Minnetonka, MN, USA) leads to a
      reduction in CM volume in patients undergoing diagnostic coronary angiography.
      METHODS: Patients scheduled for a diagnostic coronary angiogram were randomised
      to angiography with or without the DyeVertTM system. The primary efficacy
      endpoint was mean CM volume. Image quality was evaluated by an independent
      reviewer blinded to treatment allocation. RESULTS: A total of 96 patients
      underwent randomisation. Baseline characteristics were well balanced between
      groups. Use of the DyeVertTM system resulted in a significant 41.0% reduction in
      CM volume (36.9+/-10.9mL versus 62.5+/-12.7mL, p<0.001). Image quality using the
      DyeVertTM system was non-inferior compared to control (p=0.03). There were no
      device-related adverse events. CONCLUSIONS: The DyeVertTM system leads to
      significant reduction in CM volume in patients undergoing diagnostic coronary
      angiography, while maintaining image quality.

PMID- 29373138
TI  - Individual and contextual factors for the child abuse potential of Croatian
      mothers: The role of social support in times of economic hardship.
AB  - The study assessed mothers' risk for abusing their children in middle adolescence
      in relation to individual and contextual factors during the economic crisis in
      Croatia. Socioeconomic status of mothers, family economic pressure, and mothers'
      exposure to stress were measured. Special attention was given to the perceived
      availability of social support as one of protective factors potentially buffering
      the negative impact of risks of child abuse. The community sample included 746
      mothers (Mage = 42.85; SDage = 5.319). The results showed that the risk of child
      abuse is higher for mothers with lower education, those who perceive themselves
      as suffering greater family economic hardship, those who have experienced a
      higher number of stressful events, and those with lower social support. When the
      mothers perceive a lower availability of social support, the effects of exposure
      to cumulative risk, namely the combination of socioeconomic status, economic
      pressure, and exposure to stress, are stronger. Since social support proved to be
      one of the key protective factors in the relationship between adverse life
      circumstances and parenting, the development of effective and non-stigmatized
      interventions aiming to increase social support, positive social relationships,
      and adequate parenting practices for parents facing economic hardship is an
      important direction for future family policy measures.

PMID- 29373137
TI  - Indicators of nutrient pollution in Long Island, New York, estuarine
      environments.
AB  - Roughly eight million people live on Long Island, including Brooklyn and Queens,
      and despite improvements in wastewater treatment, nearly all its coastal
      waterbodies are impaired by excessive nitrogen. We used nutrient stoichiometry
      and stable isotope ratios in estuarine biota and soils to identify water
      pollution hot spots and compare among potential indicators. We found strong
      gradients in delta15N values, which were correlated with watershed land cover,
      population density, and wastewater discharges. Weaker correlations were found for
      delta13C values and nutrient stoichiometric ratios. Structural equation modeling
      identified contrasts between western Long Island, where delta15N values depended
      on watershed population density, and eastern Long Island where delta15N values
      reflected agriculture and sewage discharges. These results illustrate the use of
      stable isotopes as water quality indicators, and establish a baseline against
      which the efficacy of strategies to reduce nutrients can be measured.

PMID- 29373139
TI  - Sinus pericranii: early infant diagnosis.

PMID- 29373140
TI  - [Foot drop: an iatrogenic complication of spinal anesthesia].
AB  - BACKGROUND AND OBJECTIVES: Foot drop in postoperative period is very rare after
      spinal anesthesia. Early clinical assessment and diagnostic interventions is of
      prime importance to establish the etiology and to start appropriate management.
      Close follow-up is warranted in early postoperative period in cases when patient
      complain paresthesia or pain during needle insertion or drug injection. CASE
      REPORT: A 22-year-old male was undergone lower limb orthopedic surgery in spinal
      anesthesia. During shifting from postoperative ward footdrop was suspected during
      routine assessment of regression of spinal level. Immediately the patient was
      referred to a neurologist and magnetic resonance imaging was done, which was
      inconclusive. Conservative management was started and nerve conduction study was
      done on the 4th postoperative day that confirmed pure motor neuropathy of right
      peroneal nerve. Patient was discharged with ankle splint and physiotherapy after
      slight improvement in motor power (2/5). CONCLUSIONS: Foot drop is very rare
      after spinal anesthesia. Any suspected patient must undergo emergent neurological
      consultation and magnetic resonance imaging to exclude major finding and need for
      early surgical intervention.

PMID- 29373141
TI  - [The influence of the menstrual cycle on acute and persistent pain after
      laparoscopic cholecystectomy].
AB  - BACKGROUND AND OBJECTIVES: Fluctuations of female sex hormones during menstrual
      cycle influence pain perception. Endogenous pain inhibition is impaired in
      follicular phase of menstrual cycle. We tested the primary hypothesis that the
      women having surgery during their follicular phase have more acute pain and
      require higher opioids than those in the luteal phase, and secondarily we tested
      that women who have surgery during their follicular phase have more incisional
      pain at 3 month postoperatively. METHODS: 127 adult females having laparoscopic
      cholecystectomy were randomized to have surgery during the luteal or follicular
      phase of their menstrual cycle. Standardized anesthesia and pain management
      regimen was given to all patients. Pain and analgesic consumption were evaluated
      in post-anesthesia care unit and every 4h in the first 24h. Adverse effects were
      questioned every 4h. Time to oral intake and ambulation were recorded. Post
      surgical pain, hospital anxiety, depression scale, SF-12 questionnaire were
      evaluated at 1 and 3 month visits. RESULTS: There was no difference in acute pain
      scores and analgesic consumption through the 24h period, Visual Analog Scale at
      24h was 1.5+/-1.5cm for follicular group 1.4+/-1.7cm for luteal group (p=0.57).
      Persistent postoperative pain was significantly more common one and at three
      month, with an incidence was 33% and 32% in the patients at follicular phase
      versus 16% and 12% at luteal phase, respectively. The Visual Analog Scale at one
      and at three month was 1.6+/-0.7cm and 1.8+/-0.8cm for follicular group and 2.7+/
      1.3cm and 2.9+/-1.7cm in the luteal group (p=0.02), respectively. There were no
      significant differences between the groups with respect to anxiety and
      depression, SF-12 scores at either time. Nausea was more common in follicular
      phase group (p=0.01) and oral feeding time was shorter in follicular phase (5.9+/
      0.9h) than in luteal phase (6.8+/-1.9h, p=0.02). CONCLUSIONS: Although persistent
      postoperative pain was significantly more common one and three months after
      surgery the magnitude of the pain was low. Our results do not support scheduling
      operations to target particular phases of the menstrual cycle.

PMID- 29373142
TI  - Respuesta de los autores.

PMID- 29373143
TI  - [Antipneumococcal vaccination in Catalonian adults: Vaccine coverages and
      adequacy to distinct guideline recommendations].
AB  - OBJECTIVES: To know antipneumococcal vaccination coverages among Catalonian
      adults and evaluate the adequacy of vaccine use according to 3 distinct current
      vaccination guidelines. DESIGN: Population-based cross-sectional study. SETTING:
      Primary Health Care. Catalonia, Spain. PARTICIPANTS: A total of 2,033,465
      individuals>=50 years-old registered in the Catalonian Health Institute. MAIN
      MEASUREMENTS: Vaccination status for the 23-valent pneumococcal polysaccharide
      vaccine (PPV23) and/or the 13-valent pneumococcal conjugate vaccine (PCV13) was
      revised at 1/01/2015. Adequacy of vaccination status was determined according to
      3 distinct vaccination recommendation guidelines: Spanish Ministry of Health
      (basically coinciding with Catalonian Health Institute's recommendations),
      Spanish Society of Family Physicians (semFYC) and Centers for Disease Control and
      Prevention (CDC). RESULTS: Overall, 789,098 (38.8%) persons had received PPV23
      and 5,031 (0.2%) had received PCV13. PPV23 coverage largely increased with
      increasing age (4.8% in 50-59 years, 35.5% in 60-69 years, 71.9% in 70-79 years
      and 79.5% in>=80 years; P<.001), whereas PCV13 coverage was very small in all age
      groups. Considering the 3 analysed vaccine guidelines a 46.1% of the overall
      study population were adequacy vaccinated according to Spanish Ministry's
      recommendations, 19.3% according to semFYC's recommendations and 4.6% according
      to CDC's recommendations. CONCLUSION: PPV23 coverage among Catalonian adults may
      be considered as intermediate, but PCV13 coverage is very small. The
      institutional recommendations (Spanish Ministry) are more followed than
      corporative (semFYC) or less local (CDC) recommendations in clinical practice.

PMID- 29373144
TI  - Sialendoscopy for sialolithiasis in children: 4-8 years follow up.
AB  - Sialolithiasis is rare in children, there are no guidelines for its treatment,
      and there are few, if any, long term follow-up studies. We report a retrospective
      review of medical records of children who were treated for sialolithiasis by
      sialendoscopy between 1 January 2007 and 31 December 2011, and who have been
      followed up for 4-8 years. Personal and clinical details, including age, sex,
      symptoms, whether the lithiasis was parotid or submandibular, the technique of
      sialendoscopy and complications, were recorded. Twenty-six children (30 sides)
      were successfully treated by sialendoscopy between 2007 and 2011 (mean (range)
      age 12 (3-17) years). Stones were removed from the parotid gland in four patients
      and the submandibular gland in 22. The main indication for sialendoscopy was
      swelling of the salivary gland during meals. Twenty-six procedures were done
      endoscopically. Twelve were treated with a wire basket alone, 10 by the combined
      approach, and laser was used in eight. Four patients developed complications, but
      without long-term effects. During follow-up of 4-8 years there were no recurrent
      swellings. We conclude that endoscopic treatment of stones in childhood is an
      efficient and conservative option for salivary glands, has few complications and
      no clinical recurrence at medium to long-term follow-up.

PMID- 29373145
TI  - Core Needle Biopsy of an Anterior Mediastinal Thymoma: Creation of a Safe Access
      Route by Hydrodissection.

PMID- 29373146
TI  - Alterations in male reproductive hormones in relation to environmental DDT
      exposure.
AB  - DDT [1, 1, 1-trichloro-2,2-bis (p-chlorophenyl)-ethane] compounds are used for
      indoor residual spraying (IRS) to control malaria mosquitoes. DDT is an endocrine
      disruptor chemical in experimental conditions, but little is known of adverse
      effects related to living conditions with continual uptake across a time span by
      all possible means of exposure. Based on estrogenic and/or anti-androgenic
      effects found in animal studies, we hypothesized that chronic DDT/DDE exposures
      in men may be associated with changes in male reproductive hormones. We tested
      this hypothesis by compared the magnitude and direction of associations between
      DDT and DDE (1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene) concentrations and
      male reproductive hormones in samples collected from IRS and non-IRS areas. We
      sampled a cross-section of 535 men (aged 18-40 years). Men living in IRS villages
      had significantly higher DDT and DDE concentrations compared with men from non
      IRS villages. Men with DDT or DDE uptake (as reflected in detectable plasma
      concentrations) had significantly higher total-, free and bio-available
      testosterone (T), and lower follicle stimulating hormone (FSH) concentrations;
      lower luteinizing hormone (LH) concentrations were only evident with DDT uptake.
      To establish a dose-dependent effect, four sub-categories were defined. Men with
      the highest DDT (74-519 MUg/g) and DDE (173-997 MUg/g) concentrations had
      significantly higher total-, free and bio-available T, and lower FSH
      concentrations compared with subjects with non-detectable isomer concentrations.
      Estradiol concentrations were significantly higher in men with DDT and DDE
      concentrations in both the third (DDE: 27-172 MUg/g; DDT: 5-73 MUg/g) and fourth
      (DDE: 173-997 MUg/g; DDT: 74-519 MUg/g) categories. Men from IRS villages were
      significantly more likely to have higher total and bioavailable T as well as
      higher estradiol concentrations OR = 2.5 (95% CI 1.2, 3.2); OR 2.5 (95% CI 1.6,
      4.0) and OR = 2.3 (95% CI 1.3, 4.1) compared to men from non-IRS villages, after
      controlling for age, BMI, personal use of pesticides, and smoking. Men living in
      IRS villages with life-long exposure (17.6 (+/-6) years) at the current residence
      with multiple exposure modalities incurred the highest degree of physiological
      imbalance over and above circulating isomer concentrations. Further studies are
      needed to elucidate the health implications of these findings.

PMID- 29373147
TI  - [Examining and touching the skin].

PMID- 29373148
TI  - Effect of an enhanced recovery after surgery protocol in patients undergoing
      pancreaticoduodenectomy: A randomized controlled trial.
AB  - BACKGROUND & AIMS: Evidence of the advantages of enhanced recovery after surgery
      (ERAS) protocols following pancreaticoduodenectomy (PD) is limited. The aim of
      this study was to examine the efficiency of ERAS protocols in patients following
      PD. METHODS: Between June 2014 and October 2016, patients undergoing PD were
      randomly assigned to receive ERAS protocols or standard care. The primary
      endpoint was the postoperative length of stay. Secondary endpoints included
      postoperative complications, postoperative quality-of-life (QoR-40J),
      readmission, and medical cost. RESULTS: Of 80 eligible patients, 74 were analyzed
      in intention-to-treat principles: 37 in the control group and 37 in the ERAS
      group. The mean length of stay in the ERAS group was significantly shorter than
      that in the control group (20.1 +/- 5.4 vs 26.9 +/- 13.5 days, P < 0.001). The
      ERAS group had a significantly lower percentage of postoperative complications
      (32.4% vs 56.8%, P = 0.034) and readmissions (0% vs 8.1%, P = 0.038). Quality-of
      life was also significantly better in the ERAS group (184 +/- 12.4 vs 177 +/-
      14.5, P = 0.022). The total medical cost was lower in the ERAS group, but not
      significantly ($25,445 +/- 5065 vs $28,384 +/- 9999, P = 0.085). CONCLUSIONS: The
      optimization of ERAS protocols in patients undergoing PD is safe and accelerates
      perioperative recovery and quality-of-life, thereby reducing the length of stay.
      Morbidity was significantly decreased in the ERAS group without compromising
      surgical outcome. REGISTRATION NUMBER: UMIN000014068.

PMID- 29373149
TI  - Comment on: Lifestyle predictors of obese and non-obese patients with
      nonalcoholic fatty liver disease: A cross-sectional study.

PMID- 29373150
TI  - Overexpressed SIRT6 attenuates cisplatin-induced acute kidney injury by
      inhibiting ERK1/2 signaling.
AB  - Sirtuin 6 (SIRT6) is a NAD+-dependent deacetylase associated with numerous
      aspects of health and physiology. Overexpression of SIRT6 has emerged as a
      protector in cardiac tissues against pathologic cardiac hypertrophy. However, the
      mechanism of this protective effect is not fully understood. Here, both in vivo
      and in vitro results demonstrated that SIRT6 overexpression can attenuate
      cisplatin-induced kidney injury in terms of renal dysfunction, inflammation and
      apoptosis. In addition, SIRT6 knockout aggravated kidney injury caused by
      cisplatin. We also found that SIRT6 bound to the promoters of ERK1 and ERK2 and
      deacetylated histone 3 at Lys9 (H3K9) thereby inhibiting ERK1/2 expression.
      Furthermore, inhibition of ERK1/2 activity eliminated aggravation of kidney
      injury caused by SIRT6 knock out. Thus, our findings uncover the protective
      effect of SIRT6 on the kidney and define a new mechanism by which SIRT6 regulates
      inflammation and apoptosis. This may provide a new therapeutic target for kidney
      injury under stress.

PMID- 29373151
TI  - Reply to Dr Wael Agur.

PMID- 29373152
TI  - Management of female stress urinary incontinence.

PMID- 29373153
TI  - Diaphragmatic Ultrasound Correlates with Inspiratory Muscle Strength and
      Pulmonary Function in Healthy Subjects.
AB  - Diaphragm ultrasound (DUS) has been used to identify diaphragm dysfunction.
      However, its correlations with respiratory strength and lung function are
      unclear, even in healthy patients. A total of 64 healthy patients (30 males) had
      lung function and inspiratory strength (maximal inspiratory pressure and sniff
      nasal inspiratory pressure) measured. Gastric and oesophageal pressures were
      measured in a subgroup (n = 40). DUS was characterized by mobility (quiet
      breathing [QB] and deep breathing [DB]) and thickness (at functional residual
      capacity [ThFRC] and total lung capacity [ThTLC]). We calculated the thickening
      fraction (TF). During QB, DUS was similar between sexes. However, during DB,
      females had lower mobility, thickness and TF than males. Mobility at DB, ThTLC
      and TF significantly correlated with lung function and inspiratory strength.
      These correlations were affected by sex. DUS correlated with inspiratory gastric
      pressure. In healthy patients, DUS correlated with lung function and inspiratory
      strength during DB. Significant differences between genders were noticeable when
      DUS was performed during DB.

PMID- 29373154
TI  - Characteristic Echocardiographic Manifestations of Behcet's Disease.
AB  - The objective of this study was to determine the characteristic echocardiographic
      manifestations of Behcet's disease. Ninety-seven Behcet's patients admitted to
      our hospital from January 2002 to December 2016 were retrospectively analyzed.
      There were 63 patients (64.9%) with cardiac involvement; these included 47 men
      (74.6%) and 16 women (25.4%). Of these 63 patients, most (74.6%) exhibited
      valvular lesions, especially aortic regurgitation. The primary characteristic
      manifestations of valves were cusp prolapse with aneurysmal changes, vegetation
      like lesions and echo-free spaces within the annulus. Second (30.0%) were aortic
      lesions, including aortic dilation or aneurysm formation, aortic pseudoaneurysm
      and coronary sinus aneurysm. Other manifestations, such as cardiac thrombosis,
      coronary arterial pseudoaneurysm, pulmonary aneurysm and pericardial effusion,
      were rare. Cardiac involvement is not uncommon in Behcet's patients, especially
      in males, and it is characterized by valvular disease, especially aortic
      regurgitation. The diagnosis of Behcet's disease should be considered when
      evaluating patients with these characteristic echocardiographic manifestations.

PMID- 29373155
TI  - Emergency Department Contribution to the Prescription Opioid Epidemic.
AB  - STUDY OBJECTIVE: We characterize the relative contribution of emergency
      departments (EDs) to national opioid prescribing, estimate trends in opioid
      prescribing by site of care (ED, office-based, and inpatient), and examine
      whether higher-risk opioid users receive a disproportionate quantity of their
      opioids from ED settings. METHODS: This was a retrospective analysis of the
      nationally representative Medical Expenditure Panel Survey from 1996 to 2012.
      Individuals younger than 18 years and with malignancy diagnoses were excluded.
      All prescriptions were standardized through conversion to milligrams of morphine
      equivalents. Reported estimates are adjusted with multivariable regression
      analysis. RESULTS: From 1996 to 2012, 47,081 patient-years (survey-weighted
      population of 483,654,902 patient-years) surveyed by the Medical Expenditure
      Panel Survey received at least 1 opioid prescription. During the same period, we
      observed a 471% increase in the total quantity of opioids (measured by total
      milligrams of morphine equivalents) prescribed in the United States. The
      proportion of opioids from office-based prescriptions was high and increased
      throughout the study period (71% of the total in 1996 to 83% in 2012). The amount
      of opioids originating from the ED was modest and declined throughout the study
      period (7.4% in 1996 versus 4.4% in 2012). For people in the top 5% of opioid
      consumption, ED prescriptions accounted for only 2.4% of their total milligrams
      of morphine equivalents compared with 87.8% from office visits. CONCLUSION:
      Between 1996 and 2012, opioid prescribing for noncancer patients in the United
      States significantly increased. The majority of this growth was attributable to
      office visits and refills of previously prescribed opioids. The relative
      contribution of EDs to the prescription opioid problem was modest and declining.
      Thus, further efforts to reduce the quantity of opioids prescribed may have
      limited effect in the ED and should focus on office-based settings. EDs could
      instead focus on developing and disseminating tools to help providers identify
      high-risk individuals and refer them to treatment.

PMID- 29373156
TI  - Initial Observations of Salivary Brain-Derived Neurotrophic Factor Levels in Rett
      Syndrome.

PMID- 29373157
TI  - New-Onset Status Epilepticus in Pediatric Patients: Causes, Characteristics, and
      Outcomes.
AB  - BACKGROUND: Many pediatric patients presenting with status epilepticus have no
      history of seizures. METHODS: We retrospectively analyzed the clinical
      characteristics of patients aged one month to 21 years who presented during six
      consecutive years with convulsive status epilepticus and without a history of
      seizures. New-onset refractory status epilepticus was defined as status
      epilepticus refractory to two lines of treatment, without an identified cause in
      the first 48 hours. RESULTS: Of 460 patients with status epilepticus, 79 (17.2%)
      presented with new-onset status epilepticus, including four (0.9%) with new-onset
      refractory status epilepticus. Of those patients, 54.4% were female, and the
      median age was 3.5 years (IQR: 1.08 to 6.75). The median seizure duration was 20
      minutes (IQR: 10 to 40 minutes). Etiology was unknown in 36.7%, symptomatic in
      30.3%, provoked in 16.5%, and provoked with an existing symptomatic etiology in
      16.5%. Patients were followed for a median duration of 63 months (IQR: 21 to 97).
      The mortality rate was 3.8%. Of 55 patients who were developmentally normal at
      baseline, 29.1% had a significant cognitive impairment at the last follow-up, and
      20% had academic difficulties or behavioral problems. Patients with symptomatic
      etiology had greater odds of having cognitive and behavioral problems compared
      with patients with unknown etiology (odds ratio = 3.83, P = 0.012). CONCLUSIONS:
      Patients with new-onset status epilepticus are at risk for recurrent seizures,
      recurrent status epilepticus, death, and subsequent cognitive-behavioral
      impairment. Specific monitoring and care interventions might be required in this
      high-risk population.

PMID- 29373158
TI  - Cardiac Arrest Following Abdominal Catastrophe in a Toddler.

PMID- 29373159
TI  - Single-ended prediction of listening effort using deep neural networks.
AB  - The effort required to listen to and understand noisy speech is an important
      factor in the evaluation of noise reduction schemes. This paper introduces a
      model for Listening Effort prediction from Acoustic Parameters (LEAP). The model
      is based on methods from automatic speech recognition, specifically on
      performance measures that quantify the degradation of phoneme posteriorgrams
      produced by a deep neural net: Noise or artifacts introduced by speech
      enhancement often result in a temporal smearing of phoneme representations, which
      is measured by comparison of phoneme vectors. This procedure does not require a
      priori knowledge about the processed speech, and is therefore single-ended. The
      proposed model was evaluated using three datasets of noisy speech signals with
      listening effort ratings obtained from normal hearing and hearing impaired
      subjects. The prediction quality was compared to several baseline models such as
      the ITU-T standard P.563 for single-ended speech quality assessment, the American
      National Standard ANIQUE+ for single-ended speech quality assessment, and a
      single-ended SNR estimator. In all three datasets, the proposed new model
      achieved clearly better prediction accuracies than the baseline models;
      correlations with subjective ratings were above 0.9. So far, the model is trained
      on the specific noise types used in the evaluation. Future work will be concerned
      with overcoming this limitation by training the model on a variety of different
      noise types in a multi-condition way in order to make it generalize to unknown
      noise types.

PMID- 29373160
TI  - Visualization of age-related vascular alterations in facial skin using optical
      coherence tomography-based angiography.

PMID- 29373161
TI  - Quantitative microstructural cerebral changes in neurofibromatosis type 1.
AB  - OBJECTIVES: To evaluate microstructural cerebral changes in children with
      neurofibromatosis type 1 (NF1) based on T2 relaxation time measurements at
      3Tesla. METHODS: From our dataset of pediatric MRI examinations at 3T 19
      pediatric NF1 patients (1.9-14.3 years of age, 9 girls, 10 boys) were
      retrospectively selected and compared with the previously published group of 44
      healthy children (0-16 years of age). MRI examination included a triple echo TSE
      sequence as basis for T2 maps. T2 relaxation times were measured in 37 brain
      regions. RESULTS: Compared with healthy controls, T2 relaxation times had the
      tendency to be increased by 1.01% (GM) to 11.85% (dentate nucleus) for NF1
      patients. Only in posterior limb of the internal capsule and parietooccipital
      white matter values were reduced. No differences were observed between both
      hemispheres. Overall, no strong evidence supporting a difference between NF1
      patients with and without optic glioma or with normal and impaired
      neuropsychological development was observed. CONCLUSIONS: Using T2 relaxation
      times it was possible to describe measurable microstructural differences in
      multiple brain regions between NF1 patients and healthy children regardless of
      whether signal abnormalities were visible on conventional images.

PMID- 29373162
TI  - Altered functional connectivity in post-ischemic stroke depression: A resting
      state functional magnetic resonance imaging study.
AB  - OBJECTIVE: In previous studies, post-stroke depression (PSD) was found to be
      related to stroke characteristics as well as social and psychological factors.
      This study identified altered functional connectivity (FC) in patients with PSD
      at the subacute phase in three brain networks: default mood network (DMN),
      cognitive control network (CCN), and affective network (AN). The correlation
      between FC and the severity of PSD was investigated. MATERIALS AND METHODS:
      Resting-state functional magnetic resonance image (rs-fMRI) was performed on 26
      PSD patients (6 females), 24 stroke patients without depression (5 females), and
      24 age-matched normal controls (6 females) all aged 40-75 years. The FC values of
      DMN, CCN, and AN were calculated and compared among the three groups. The
      Hamilton Depression Rating Scale (HDRS) (17 items) was employed and the score was
      correlated with FC in the PSD group. RESULTS: The FCs of the three networks were
      altered in PSD patients at the subacute phase compared to stroke patients without
      depression and normal controls (NC). Moreover, the left inferior parietal gyrus,
      the left orbital part of inferior frontal gyrus, and left angular gyrus (which
      indicated altered FC) were significantly correlated with HDRS scores in PSD
      patients. CONCLUSIONS: Alteration of the three neural networks might be
      correlated with the development of PSD at the subacute phase of stroke.

PMID- 29373163
TI  - Social Determinants of LGBT Cancer Health Inequities.
AB  - OBJECTIVES: To describe the extant literature on social determinants of health as
      they relate to the cancer disparities and to highlight the research findings
      relating to lesbian, gay, bisexual, and transgender (LGBT) populations. DATA
      SOURCES: Published scientific literature and clinical literature, and published
      reports from the World Health Organization and US Department of Health and Human
      Services. CONCLUSION: The larger literature on health inequities is moving beyond
      individual-level predictors of risk to evaluate the influence of social
      determinants of health on the persistent health inequalities in a population. As
      it has for other groups, additional research into social determinants of health
      for LGBT persons of color may play an important role in identifying and reducing
      cancer inequities for this group. IMPLICATIONS FOR NURSING PRACTICE: Increased
      awareness of the factors that contribute to health inequities for the LGBT
      population may provide insight into improving patient-provider relationships with
      LGBT patients. A large body of experiential and clinical knowledge positions
      nurses to conduct meaningful research to expand the current understanding of the
      social determinants of LGBT cancer health inequities.

PMID- 29373165
TI  - Relapsing Pott disease caused by Mycobacterium heckeshornense in a well
      controlled HIV-infected patient.

PMID- 29373164
TI  - High frequency jet ventilation during endolaryngeal surgery: Risk factors for
      complications.

PMID- 29373166
TI  - Ultrastructural study on the embryonic development of the orthokeratinized
      epithelium and its cornified layer (lingual nail) on the ventral surface of the
      lingual apex in the domestic duck (Anas platyrhynchos f. domestica).
AB  - The lingual nail as the cornified layer of the orthokeratinized epithelium in
      birds is responsible for the collection of solid food by pecking. The aim of the
      present study is to determine the manner of orthokeratinized epithelium
      development and assess the degree of readiness of the epithelium to fulfill its
      mechanical function at hatching. Three developmental phases are distinguished,
      i.e. embryonic, transformation and pre-hatching stage. In the embryonic stage
      lasting until day 13 of incubation the epithelium is composed of several layers
      of undifferentiated cells. During the transformation stage, from day 14 to 20 of
      incubation, the epithelium becomes differentiated to form three layers. A
      characteristic feature is the formation of osmophilic granules in the superficial
      layer, referred to as periderm granules. Until the pre-hatching stage the fibrous
      cytoskeleton of epithelial cells and an impermeable epithelial barrier are
      gradually developed. In the pre-hatching stage, a cornified lingual nail is
      formed, while the periderm is exfoliated. At hatching the orthokeratinized
      epithelium and lingual nail are fully developed and ready to perform feeding
      activities. The presence of periderm, similarly as in the epidermis, indicates
      the ectodermal derivation of the oral cavity epithelium. Moreover, occurrence of
      osmophilic granules may be considered as evidence for the phylogenetic affinity
      of birds and reptiles.

PMID- 29373167
TI  - Do high sound pressure levels of crowing in roosters necessitate passive
      mechanisms for protection against self-vocalization?
AB  - High sound pressure levels (>120dB) cause damage or death of the hair cells of
      the inner ear, hence causing hearing loss. Vocalization differences are present
      between hens and roosters. Crowing in roosters is reported to produce sound
      pressure levels of 100dB measured at a distance of 1m. In this study we measured
      the sound pressure levels that exist at the entrance of the outer ear canal. We
      hypothesize that roosters may benefit from a passive protective mechanism while
      hens do not require such a mechanism. Audio recordings at the level of the
      entrance of the outer ear canal of crowing roosters, made in this study, indeed
      show that a protective mechanism is needed as sound pressure levels can reach
      amplitudes of 142.3dB. Audio recordings made at varying distances from the
      crowing rooster show that at a distance of 0.5m sound pressure levels already
      drop to 102dB. Micro-CT scans of a rooster and chicken head show that in roosters
      the auditory canal closes when the beak is opened. In hens the diameter of the
      auditory canal only narrows but does not close completely. A morphological
      difference between the sexes in shape of a bursa-like slit which occurs in the
      outer ear canal causes the outer ear canal to close in roosters but not in hens.

PMID- 29373168
TI  - Risk factors of urinary tract infection caused by extended spectrum beta
      lactamase-producing Escherichia coli in emergency department.
AB  - OBJECTIVES: The incidence of urinary tract infection (UTI) due to extended
      spectrum beta-lactamase (ESBL)-producing Escherichia coli has increased over
      recent years. Initial empirical therapy is often ineffective for these resistant
      isolates resulting in prolonged hospitalization and increased mortality. This
      study was conducted to determine the risk factors of UTI caused by ESBL E. coli
      in the emergency department (ED). METHODS: This is a retrospective case-control
      study at a university hospital in Korea with UTI patients who visited ED between
      June 2015 and December 2016. We compared case patients with ESBL E. coli UTI (n =
      50) to control patients with non-ESBL-producing E. coli UTI (n = 100), which were
      matched for age and sex. Multivariate logistic regression analysis was used to
      explore risk factors. RESULTS: Our study showed that hospital-acquired infection
      (OR = 3.86; 95% CI = 1.26-11.8; p = .017), prior UTI within 1 year (OR = 3.26;
      95% CI = 1.32-8.05; p = .010), and underlying cerebrovascular disease (OR = 3.24;
      95% CI = 1.45-7.25; p = .004) were independent risk factors for acquisition of
      ESBL-producing E. coli. Notably, 35 (70%) out of 50 case patients had community
      acquired infection, and 68% and 54% of ESBL E. coli were resistance to
      ciprofloxacin and trimethoprim-sulfamethoxazole, respectively. On the contrary,
      98% of ESBL E. coli was susceptible to amikacin. CONCLUSION: The main risk
      factors identified in our study should be considered when treating UTI patients
      in ED. Amikacin may improve the outcome of empirical treatment without increasing
      carbapenem utilization.

PMID- 29373169
TI  - Xuebijing combined with ulinastation benefits patients with sepsis: A meta
      analysis.
AB  - BACKGROUND: The potential benefits and possible risks associated with Xuebijing
      when combined with ulinastatin for sepsis treatment are not fully understood.
      METHODS: Databases, such as PubMed, Web of Science, CNKI, WanFang and VIP, were
      searched to collect randomized, controlled trials. Studies were screened, data
      were extracted, and the methodological quality was assessed by two reviewers
      independently. A meta-analysis was carried out with Stata 11.0 software. RESULTS:
      A total of 16 studies involving 1192 participants were enrolled for meta-analysis
      based on the inclusion and exclusion criteria. The results showed that compared
      with the group using routine therapies and the group using a single
      administration of either ulinastatin or Xuebijing, the trial group using
      Xuebijing combined with ulinastatin was significantly superior in the following
      aspects: mortality (RR = 0. 54,95% CI (0. 41, 0. 70, P = .000), 7 d APACHE II
      (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), duration of mechanical ventilation
      (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), average length of time in the
      intensive care unit (SMD = -1.21, 95%CI (-1.62, -0.80), P = .000), incidence of
      multiple organ dysfunction syndromes (RR = 0. 54, 95% CI (0.41, 0. 70, P = .000),
      interleukin-6 (SMD = -1.36,95%CI (-2.46, -0.27), P = .000), lipopolysaccharide
      (SMD = -9.92, 95%CI (-11.7, -7.90), P = .006), and procalcitonin (SMD = -0.30,
      95%CI (-0.34, -0.26), P = .012). CONCLUSIONS: Our results found that Xuebijing
      when combined with ulinastatin was superior to both routine therapies and the
      single administration of either ulinastatin or Xuebijing. This finding provides a
      new therapeutic option for the treatment of sepsis.

PMID- 29373170
TI  - Time crunch: increasing the efficiency of assessment of technical surgical skill
      via brief video clips.
AB  - BACKGROUND: Video review for assessment of surgical performance is gaining
      popularity but is time consuming for busy expert reviewers, making review delays
      inevitable. Decreasing review time and including nonexpert reviewers may
      facilitate more timely reviews. We hypothesized that a shorter duration video
      clip would not affect the quality of expert ratings compared with full-length
      review. A secondary aim was to examine the reliability between expert and novice
      raters and how it was affected by video clip duration. METHODS: Videos of
      laparoscopic suturing performed on a live porcine model by premedical students,
      surgery residents, and fully trained surgeons were edited into 3 different
      durations: full, part, and 30-second versions. Video clips (n = 36) were reviewed
      by experienced surgeons (n = 3) and novice volunteers (n = 4) using the validated
      Global Operative Assessment of Laparoscopic Skills (GOALS) assessment. Videos
      were assigned randomly during 3 review cycles held 1 week apart. Each cycle
      included 1 iteration of the 12 performance videos. We assessed the impact of the
      duration of the video on reviewer scores and inter-rater reliability. RESULTS:
      Variance in scores for 2 of 4 GOALS domains was dependent on the duration of the
      video clip (P < .05). Total GOALS scores were greater for part and 30-second
      clips compared with full clips (P < .05). Inter-rater reliability was greatest
      for full clips (intraclass correlation = 0.68) and decreased significantly for
      shorter clips. CONCLUSION: Our hypothesis was rejected as shorter video durations
      for surgical performance assessment led to inflated reviewer ratings both for
      expert and novice reviewers. Shortening duration of the video cannot be
      recommended for accurate performance assessment.

PMID- 29373171
TI  - Evolution of a level I pediatric trauma center: Changes in injury mechanisms and
      improved outcomes.
AB  - BACKGROUND: Trauma is the leading cause of mortality among children, underscoring
      the need for specialized child-centered care. The impact on presenting mechanisms
      of injury and outcomes during the evolution of independent pediatric trauma
      centers is unknown. The aim of this study was to evaluate the impact of our
      single center transition from an adult to American College of Surgeons-verified
      pediatric trauma center. METHODS: A retrospective analysis was performed of 1,190
      children who presented as level I trauma activations between 2005 and 2016.
      Patients were divided into 3 chronological treatment eras: adult trauma center,
      early pediatric trauma center, and late pediatric trauma center after American
      College of Surgeons verification review. Comparisons were made using Pearson
      chi2, Wilcoxon rank sum, and Kruskal-Wallis tests. RESULTS: The predominant
      mechanism of injury was motor vehicle crash, with increases noted in
      assault/abuse (2% adult trauma center, 11% late pediatric trauma center). A
      decrease in intensive care admissions was identified during late pediatric trauma
      center compared with early pediatric trauma center and adult trauma center (51%
      vs 62.4% vs 67%, P < .001), with concomitant increases in admissions to the floor
      and immediate operative interventions, but overall mortality was unchanged.
      CONCLUSION: Transition to a verified pediatric trauma center maintains the safety
      expected of the American College of Surgeons certification, but with notable
      changes identified in mechanism of injury and improvements in resource
      utilization.

PMID- 29373172
TI  - Identifying quality markers of a safe surgical ward: An interview study of
      patients, clinical staff, and administrators.
AB  - BACKGROUND: Postoperative care quality is variable. Risk-adjusted mortality rates
      differ between institutions despite comparable complication rates. This indicates
      that there are underlying factors rooted in how care is delivered that determines
      patient safety. This study aims to evaluate systematically the surgical ward
      environment with respect to process-driven and structural factors to identify
      quality markers for safe care, from which new safety metrics may be derived.
      METHODS: Semistructured interviews of clinicians, nurses, patients and
      administrators were undertaken for the study. RESULTS: In the study, 97% of staff
      members recognized the existence of variation in patient safety between surgical
      wards. Four main error-prone processes were identified: ward rounds (57%),
      medication prescribing and administration (49%), the presence of outliers (43%),
      and deficiencies in communication between clinical staff (43%). Structural
      factors were categorized as organizational or environmental; organizational
      included shortage in staffing (39%) and use of temporary staff (27%).
      Environmental factors considered layout and patient visibility to nurses (49%) as
      well as cleanliness (29%). Safety indicators identified included staff experience
      level (31%), overall layout of the ward, cleanliness and leadership (all 27%
      each). The majority of patients (87%) identified staff attentiveness as a safety
      indicator. CONCLUSION: This study demonstrates that there are a number of factors
      that may contribute to safety on the surgical ward spanning multiple processes,
      organizational, and environmental factors. Safety indicators identified across
      all these categories presents an opportunity to develop broader and more
      effectual safety improvement measures focusing on multiple areas simultaneously.

PMID- 29373173
TI  - Synchronization of cyclic and acyclic embryo recipient mares with donor mares.
AB  - This study compared hormone treatments given to mares during anestrus, spring
      transition, and different stages of the estrous cycle, by assessing uterine
      features and pregnancy rates after embryo transfer (ET). Embryo recipient mares
      (n = 160) were equally arranged as follows: G1-spontaneous ovulation (control),
      G2-anestrus, G3-spring transition, G4-early estrus, G5-estrus, G6-diestrus, G7
      early diestrus treated with a dose of dinoprost, and G8-early diestrus treated
      with two doses of dinoprost. At treatment initiation (Day-4), G2-7 were given
      dinoprost and estradiol-17beta, thereafter, estradiol-17beta was repeated on Days
      3,-2, and -1. On Day0, mares received long-acting altrenogest. Then, each mare
      had one ET performed from Day + 3 to Day + 8 after altrenogest. Immediately
      before the ET, mares received a boost of altrenogest and had uterine features
      assessed. Pregnant mares on each of the checks (by 7, 30, 60, and 120d after ET)
      were maintained on weekly injections of LA-P4 until 120d. G8 received similar
      management, but dinoprost was repeated on Day-3. G1-G6 and G8 displayed uterine
      edema and satisfactory pregnancy rates >=65%. Repeating dinoprost to G8 likely
      ensured proper luteolysis and response to estrogen as determined by higher
      uterine edema scores and pregnancy rates than G7 (p < .05). Our results were
      consistent with previous studies and other successful commercial ET programs
      (except G7), thus, demonstrating the usefulness of the hormone treatments
      described herein to synchronize embryo recipient mares with donor mares. Thus, we
      foresee that other groups may use the strategies described herein for the
      management of embryo recipient mares.

PMID- 29373174
TI  - Neutrophil gelatinase-associated lipocalin in patients with sarcoidosis.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein
      that is involved in the innate immune system and increased expression has been
      detected in diverse diseases. Sarcoidosis is a systemic granulomatous disorder
      and its clinical course and prognosis are changeable and highly divergent. This
      study aimed to examine the expression of NGAL in patients with sarcoidosis. In
      addition, we examined whether NGAL could serve as a marker of disease activity
      and prognosis. METHODS: Ninety-six sarcoidosis patients were studied. Serum
      samples collected at the time of diagnosis were examined for NGAL by cellular
      enzyme-linked immunosorbent assay. The level of NGAL was compared with clinical,
      radiological and laboratory data. RESULTS: Patients with sarcoidosis had
      significantly higher levels of NGAL (the median [interquartile range] was 35.1
      ng/mL [23.5-60.8] in sarcoidosis patients versus 17.2 ng/mL [13.0-27.0] in the
      reference population, p < .0001). NGAL levels were not correlated with markers
      for disease activity. During the follow-up period, 26 patients (27.1%)
      deteriorated and received systemic corticosteroid therapy for organ dysfunction.
      In those patients, NGAL levels were significantly higher than in those who did
      not receive corticosteroid therapy (56.5 ng/mL [27.3-92.3] versus 34.3 ng/mL
      [23.0-53.0], p = .0201). Upon multivariate logistic regression analysis, elevated
      NGAL levels at diagnosis were associated with subsequent use of systemic
      corticosteroid therapy (hazard ratio, 1.20; 95% confidence interval, 1.09-1.31; p
      = .0004). CONCLUSION: NGAL may be a useful marker to predict the disease course
      of sarcoidosis.

PMID- 29373175
TI  - A novel point mutation affecting Asn76 of dystrophin protein leads to
      dystrophinopathy.
AB  - Mutations in the DMD gene lead to Duchenne and Becker muscular dystrophy
      (DMD/BMD). Missense mutations are rare cause of DMD/BMD. A six-month-old male
      patient presented with mild generalized muscle weakness, hypotonia, and delayed
      motor development. Dystrophinopathy was suspected because of highly elevated
      serum creatine kinase level (1497 U/L) and tiered DMD gene analysis was
      performed. Multiplex ligation-dependent probe amplification (MLPA) assay showed
      deletion of exon 4, which could not be confirmed by another method. Sequencing of
      exon 4 revealed a novel de novo point mutation (c.227A>T, p.Asn76Ile) in the N
      terminal actin-binding domain (N-ABD) of dystrophin protein. The false positive
      MLPA result was explained by the fact that the affected nucleotide lies directly
      at the 3' ligation site of the MLPA probe. Sequencing of the whole coding region
      of DMD gene proved c.227A>T to be the sole variant being potentially pathogenic.
      According to in silico analyses the mutation was predicted to be highly
      destabilizing on N-ABD structure possibly leading to protein malfunction. Muscle
      biopsy was performed and dystrophin immunohistochemistry results were suggestive
      of BMD. Our results highlight the importance of confirmatory testing of single
      exon deletions detected by MLPA and we describe a novel, destabilizing missense
      mutation in the DMD gene.

PMID- 29373176
TI  - Evaluation of a Shorter Follow-up Time to Capture Benefit of a Trial Vocal Fold
      Augmentation.
AB  - OBJECTIVE: Trial vocal fold injection (TVFI) is employed diagnostically for
      patients with subtle glottic insufficiency to explore potential for improvement.
      Clinical experience demonstrates the time to and length of peak benefit of the
      TVFI is variable. Previous studies collected data 4 weeks or more after TVFI. The
      aim of this study was to compare subjectively successful and unsuccessful TVFI
      patient groups. It is hypothesized that patients with subjectively reported
      success will also have significant improvements in Voice Handicap Index-10 (VHI
      10), phase closure percentage, and aerodynamic measures 2 weeks after trial
      augmentation. METHODS/DESIGN: Subjects with glottic insufficiency were included
      in this retrospective review if they underwent office-based, per-oral vocal fold
      injection augmentation specifically for trial purposes. Patients were divided
      into "successful" and "unsuccessful" groups based on their subjective experience
      during the 2-week post-TVFI period. VHI-10, subjective report, phase closure
      evaluation using frame-by-frame analysis, and aerodynamic data were collected pre
      and 2 weeks post-TVFI. RESULTS: Of the subjects, 15 of 23 (65%) reported a
      successful subjective improvement of their symptom, whereas 8 (35%) were
      unsuccessful (only partial improvement or no improvement). The number of subjects
      with an improvement in VHI-10 by 5 or more points was not significantly different
      between groups. The number of subjects that demonstrated complete, long phase
      closure was significantly higher in the successful group (P = 0.021).
      CONCLUSIONS: The understanding of how to more precisely determine the success of
      TVFI remains incomplete. Subjective improvement of successful TVFI was captured
      with basic clinical questioning, yet the VHI-10 was unable to confidently
      demonstrate this reported success 2 weeks after TVFI.

PMID- 29373177
TI  - The quest for higher sensitivity in MRI through higher magnetic fields.

PMID- 29373178
TI  - Current use of beta-blockers in patients with coronary artery disease.
AB  - Beta-blockers have long comprised a cornerstone in the symptomatic treatment of
      ischemic heart disease and in the secondary prevention of myocardial infarction
      and heart failure. The majority of studies underlying the evidence of a
      beneficial effect of beta-blockers on outcomes were conducted more than 25 years
      ago. In a contemporary era where treatment strategies and secondary prophylactic
      therapy have undergone several changes, the continued role of beta-blockers in
      ischemic heart disease has been questioned, especially in the absence of heart
      failure or a recent myocardial infarction. In summary, few randomized clinical
      trials are available on the effect of beta-blockers in the reperfusion era,
      especially on hard endpoints. Likewise, the results of numerous observational
      studies and meta-analysis are conflicting, emphasizing the need for additional
      large-scale randomized clinical trials to evaluate the role of beta-blocker
      therapy in current clinical practice.

PMID- 29373179
TI  - Post-transplant outcomes in pediatric ventricular assist device patients: A
      PediMACS-Pediatric Heart Transplant Study linkage analysis.
AB  - BACKGROUND: Pediatric ventricular assist device (VAD) support as bridge to
      transplant has improved waitlist survival, but the effects of pre-implant status
      and VAD-related events on post-transplant outcomes have not been assessed. This
      study is a linkage analysis between the PediMACS and Pediatric Heart Transplant
      Study databases to determine the effects of VAD course on post-transplant
      outcomes. METHODS: Database linkage between October 1, 2012 and December 31, 2015
      identified 147 transplanted VAD patients, the primary study group. The comparison
      cohort was composed of 630 PHTS patients without pre-transplant VAD support. The
      primary outcome was post-transplant survival, with secondary outcomes of post
      transplant length of stay, freedom from infection and freedom from rejection.
      RESULTS: At implant, the VAD cohort was INTERMACS Profile 1 in 33 (23%), Profile
      2 in 89 (63%) and Profile 3 in 14 (10%) patients. The VAD cohort was older,
      larger, and less likely to have congenital heart disease (p < 0.0001). However,
      they had greater requirements for inotrope and ventilator support and increased
      liver and renal dysfunction (p < 0.0001), both of which normalized at transplant
      after device support. Importantly, there were no differences in 1-year post
      transplant survival (96% vs 93%, p = 0.3), freedom from infection (81% vs 79%, p
      = 0.9) or freedom from rejection (71% vs 74%, p = 0.87) between cohorts.
      CONCLUSIONS: Pediatric VAD patients have post-transplant outcomes equal to that
      of medically supported patients, despite greater pre-implant illness severity.
      Post-transplant survival, hospital length of stay, infection and rejection were
      not affected by patient acuity at VAD implantation or VAD-related complications.
      Therefore, VAD as bridge to transplant mitigates severity of illness in children.

PMID- 29373180
TI  - Immunotherapy, an evolving approach for the management of triple negative breast
      cancer: Converting non-responders to responders.
AB  - Immunotherapy comprises a promising new era in cancer therapy. Immune checkpoint
      inhibitors targeting either the programmed death (PD)-1 receptor or its ligand PD
      L1 were first approved by the Food and Drug Administration (FDA) for the
      management of metastatic melanoma in 2011. The approval of this class is being
      extended to include other types of immunogenic tumors. Although breast cancer
      (BC) was first categorized as non-immunogenic tumor type, there are certain
      subsets of BC that showed a high level of tumor infiltrating lymphocytes (TILs).
      Those subsets include the triple negative breast cancer (TNBC) and HER-2 positive
      breast tumors. Preliminary data from clinical trials presented promising outcomes
      for patients with advanced stage/metastatic TNBC. While the objective response
      rate (ORR) was relatively low, it is still promising because of the observation
      that the patients who respond to the treatment with immune checkpoint blockade
      have favorable prognosis and often show a significant increase in the overall
      survival. Therefore, the main challenge is to find ways to enhance the tumor
      response to such therapy and to convert the non-responders to responders. This
      will consequently bring new hopes for patients with advanced stage metastatic
      TNBC and help to decrease death tolls from this devastating disease. In the
      current review, we are highlighting and discussing the up-to-date strategies
      adopted at either the preclinical or the clinical settings to enhance tumor
      responsiveness to immunotherapy.

PMID- 29373181
TI  - The role of stereotactic body radiotherapy in reirradiation of head and neck
      cancer recurrence.
AB  - INTRODUCTION: Head and neck cancer recurrence is a therapeutic challenge due to
      the anatomical and functional constraints of the head and neck area. Stereotactic
      body radiotherapy (SBRT) is a high-precision technique of radiotherapy that
      consists of delivering a high ablative biological dose in 1-5 high-dose
      fractions, requiring a very high precision of the radiotherapy process with
      potential application in this clinical setting METHODS: Different studies that
      investigate the role of SBRT in the treatment of recurrent head and neck cancer
      have been reviewed. Indications to properly select patients for this treatment
      are presented. RESULTS: Retrospective studies and phase I-II trials with selected
      patients have shown low to moderate toxicity, with an efficacy at least similar
      to that of treatment with combinations of radiotherapy and chemotherapy. In
      selected patients, SBRT is a treatment option for recurrent head and neck cancer
      with low toxicity. DISCUSSION: New prospective studies should clarify data
      regarding the efficacy and toxicity of SBRT in head and neck cancer recurrence.

PMID- 29373182
TI  - The many-faced role of autophagy in liver diseases.

PMID- 29373183
TI  - B-Natriuretic Peptide Pathway Modulation for the Management of Heart Failure With
      Reduced Ejection Fraction.

PMID- 29373184
TI  - Dose-volume and radiobiological dependence on the calculation grid size in
      prostate VMAT planning.
AB  - This study evaluated the effects of dose-volume and radiobiological dependence on
      the calculation grid size in prostate volumetric-modulated arc therapy (VMAT)
      planning. Ten patients with prostate cancer were selected for this retrospective
      treatment planning study. Prostate VMAT plans were created for the patients using
      the 6 MV photon beam produced by a Varian TrueBEAM linac with the calculation
      grid size equal to 1, 2, 2.5, 3, 4, and 5 mm. Dose-volume histograms (DVHs) of
      targets and organs at risk were generated for different grid sizes. We calculated
      the radiobiological parameters of the tumor control probability (TCP) of clinical
      target volume (CTV) and planning target volume (PTV), and the normal tissue
      complication probability (NTCP) of organs at risk (rectal wall, rectum, bladder
      wall, bladder, left femur, and right femur). The homogeneity, conformity, and
      gradient indexes of CTV and PTV were calculated for different grid sizes. The TCP
      of PTV was found decreasing with a rate of 0.06%/mm when the calculation grid
      size increased from 1 to 5 mm. On the other hand, both NTCPs of rectal wall and
      rectum were found decreasing with rates of 0.03%/mm and 0.05%/mm, respectively,
      with an increase of grid size. The homogeneity index of PTV increased with a rate
      of 0.57/mm of the calculation grid size, whereas the conformity index of PTV
      decreased with a rate of 0.0075/mm. The gradient index of PTV was found
      increasing with a rate equal to 0.05/mm. In prostate VMAT planning, variations of
      dose-volume and radiobiological parameters with calculation grid size on PTV,
      rectal wall, and rectum were more significant than those of CTV and other organs
      at risk such as bladder wall, bladder, and femurs. Results in this study are
      important in the treatment planning quality assurance when the calculation grid
      size is varied to compromise a shorter dose computing time.

PMID- 29373185
TI  - Control of hospitals and nursing homes in France: The 2016 reform may indirectly
      improve a dysfunctional system.
AB  - In France, the supervisory bodies require hospitals and nursing homes to undergo
      various control procedures. A stack of legislation and control measures has piled
      up, with no provision for their interconnection being included in any of the
      legislation. The purpose of the article is to point to the prospects for better
      control opened up by the legislation modernising the health system adopted on 26
      January 2016. The reform will neither directly change the partitioning between
      the supervisory bodies preventing the sharing of information and the
      harmonisation of the practices in terms of control, nor change the internal
      partitioning within the supervisory body. But in hospitals, the reform will
      improve the interconnection of control of quality/control inspections/control of
      strategy using a common medical project and pooling certain cross-cutting
      functions, and implementing the control of quality for the new local hospital
      groupings as a whole. In nursing homes, the generalisation of multi-year aims and
      means contracts would allow a better interconnection of the control of strategy
      and the control of quality since it provides managers with the means of
      constructing projects for the evolution of their establishments over a period of
      time, and accompanies changes in the socio-medical offer to improve the provision
      of care. These changes would allow a more credible, coherent, useful, and
      equitable control.

PMID- 29373186
TI  - Rationalizing the introduction and use of pharmaceutical products: The role of
      managed entry agreements in Central and Eastern European countries.
AB  - This paper aims to provide an overview of the rationalization strategies for the
      introduction and use of pharmaceuticals, focusing on the role of managed entry
      agreements (MEA) in Central and Eastern European (CEE) countries, namely
      Bulgaria, the Czech Republic, Croatia, Hungary, Poland and Romania. We developed
      a conceptual framework on MEAs that was used as the basis for a standardized
      assessment questionnaire sent to country experts to capture their perceptions on
      their countries' rationalization strategies and MEAs. Our study shows that the
      main role of MEAs and other related policies embedded in the health care system
      is to limit the budget impact of drugs in all examined 6 countries. Uncertainty
      about outcomes and appropriate utilization seem to be of lower priority. Finance
      based MEAs are used by all countries. Performance-based MEAs are scarce and used
      to a limited extent by Hungary and Poland. The overall transparency of the
      existence and details of MEAs is limited. Expansion of the use and increased
      transparency of MEAs is recommended. Still, the informational infrastructure and
      competencies in implementing MEA's need to be developed further.

PMID- 29373187
TI  - The use of preventable hospitalization for monitoring the performance of local
      health authorities in long-term care.
AB  - OBJECTIVE: The objective of the study was to examine whether there are
      differences in the performance of long-term care programs between local health
      authorities, using preventable hospitalization as an indicator. METHODS: A
      retrospective cohort study compared the rate of preventable hospitalization for
      local health authorities in Tuscany (Italy) between January 2012 and September
      2016. Several administrative datasets for the patients in long-term care programs
      were linked at the individual (patient) level. Elderly disabled patients 65 years
      of age and older in long-term care programs in Tuscany from both types of
      programs: nursing homes (n = 4 196) and home care (n = 15 659) were included in
      the study. RESULTS: The rate of preventable hospitalization differed considerably
      between local health authorities. Three out twelve local health authorities had a
      significantly lower and one had a significantly higher preventable
      hospitalization rate than the regional average. CONCLUSION: There was a large
      variation in the rate of preventable hospitalization among the local health
      authorities. Applying preventable hospitalization as an indicator for quality,
      with implications for periodical audit can be used for monitoring the performance
      of a long-term care program.

PMID- 29373188
TI  - Socioeconomic status and waiting times for health services: An international
      literature review and evidence from the Italian National Health System.
AB  - In the absence of priority criteria, waiting times are an implicit rationing
      instrument where the absence or limited use of prices creates an excess of
      demand. Even in the presence of priority criteria, waiting times may be unfair
      because they reduce health care demand of patients in lower socio-economic
      conditions due to high opportunity costs of time or a decay in their health
      level. Significant evidence has shown a relationship between socioeconomic status
      and the length of waiting time. The first phase of the study involved an
      extensive review of the existent literature for the period of 2002-2016 in the
      main databases (Scopus, PubMed and Science Direct). Twenty-eight met the
      eligibility criteria. The 27 papers were described and classified. The e mpirical
      objective of this study was to determine whether socioeconomic characteristics
      affect waiting time for different health services in the Italian national health
      system. The services studied were specialist visits, diagnostics tests and
      elective surgeries. A classification tree and logistic regression models were
      implemented. Data from the 2013 Italian Health National Survey were used. The
      analysis found heterogeneous results for different types of service. Individuals
      with lower education and economic resources have a higher risk of experiencing
      excessive waiting times for diagnostic and specialist visits. For elective
      surgery, socioeconomic inequalities are present but appear to be lower.

PMID- 29373189
TI  - Patient blood management in cardiac surgery: Results.
AB  - OBJECTIVE: The main objective of the study was to evaluate the effect of
      implementing a blood-saving programme in patients undergoing elective cardiac
      surgery with an analysis of the transfusion rate and complications. MATERIALS AND
      METHODS: A single-centre, observational, retrospective, comparative study which
      included 604 consecutive patients older than 15 years old undergoing elective
      cardiac surgery. Two groups of patients were created according to whether or not
      they were included in a blood-saving protocol, and analysed between December 2012
      and July 2013 (293 patients, prep group) and April 2015 to May 2016 (311
      patients, posp group). RESULTS: The overall blood product transfusion rate was
      reduced in the posp group (89.5 vs. 67.6%; P<0.001), as well as individually: red
      blood cell concentrates (83.6%; P<0.001), fresh frozen plasma (36.2 vs. 21.2%;
      P<0.001), platelets (40.8 vs. 32.7; P<0.001). By contrast, fibrinogen use
      increased from 16.4 to 49% (P<0.001). Postoperative complications were similar in
      both groups, except for pulmonary complications (57.8 vs. 43.1%; P<0.001). Length
      of hospital stay was similar in both groups except in the Critical Care Unit with
      longer stay for the prep group (5.81+/-8.00 vs. 4.18+/-4.38; P=0.002). Mortality
      did not change. CONCLUSIONS: The implementation of a blood-saving programme in
      the cardiac surgery area has favourable consequences, such as a saving in blood
      product and a reduction of pulmonary complications, although without decreasing
      the mortality rate.

PMID- 29373190
TI  - What have we learned from reporting safety incidents in the Surgical Block?:
      Cross-sectional descriptive study of two-years of activity of a multidisciplinary
      analytical group.
AB  - BACKGROUND AND OBJECTIVES: Incident Reporting Systems (IRS) are considered a tool
      that facilitates learning and safety culture. Using the experience gained with
      SENSAR, we evaluated the feasibility and the activity of a multidisciplinary
      group analyzing incidents in the surgical patient notified to a general community
      system, that of the Observatory for Patient Safety (OPS). MATERIAL AND METHOD:
      Cross-sectional observational study planned for two years. After training in the
      analysis, a multidisciplinary group was created in terms of specialties and
      professional categories, which would analyze the incidents in the surgical
      patient notified to the OPS. Incidents are classified and their circumstances
      analyzed. RESULTS: Between March 2015 and 2017, 95 incidents were reported (4 by
      non-professionals). Doctors reported more than nurses, at 54 (56.84%) vs. 37
      (38.94%). The anaesthesia unit reported most at 46 (48.42%) (P=.025). The types
      of incidents mainly related to the care procedure (30.52%); to the preoperative
      period (42.10%); and to the place, the surgical area (48.42%). Significant
      differences were detected according to the origin of the notifier (P=.03). No
      harm, or minor morbidity, constituted 88% of the incidents. Errors were
      identified in 79%. The analysis of the incidents directed the measures to be
      taken. CONCLUSIONS: The activity undertaken by the multidisciplinary analytical
      group during the period of study facilitated knowledge of the system among the
      professionals and enabled the identification of areas for improvement in the
      Surgical Block at different levels.

PMID- 29373191
TI  - Change in the efficacy of influenza vaccination after repeated inoculation under
      antigenic mismatch: A systematic review and meta-analysis.
AB  - OBJECTIVES: To examine the effects of repeated influenza vaccination on medically
      attended influenza (MAI) and acute respiratory illness (ARI) risk according to
      the antigenic matching between vaccine and circulating virus strains. METHODS: We
      performed a systematic review and meta-analysis of randomized studies that
      compared the risk of MAI and ARI between subjects who had been vaccinated for two
      consecutive seasons (multiple vaccine group) and those who had been vaccinated in
      the current season and not in the previous season (single vaccine group).
      RESULTS: Of 1467 articles identified, eight studies covering ten seasons were
      included in meta-analyses. Six studies assessed efficacy against MAI in children,
      yielding the risk ratios (RR) of 2.04 (95% CI 1.29-3.22) when circulating strains
      mismatched vaccine strains, and 0.64 (0.33-1.22) when circulating strains matched
      vaccine strains. When stratified by vaccine types, the reduced efficacy was
      significant for live-attenuated influenza vaccine only. Three studies
      investigated efficacy against ARI in children, with the RR of 0.96 (0.81-1.15).
      The results on adults and the elderly were scarce. CONCLUSIONS: Influenza vaccine
      efficacy against mismatch strains was lower in repeatedly vaccinated children as
      compared with those vaccinated for the current season only. The scarcity of
      available studies may call for further randomized controlled trials on repeated
      influenza vaccination.

PMID- 29373193
TI  - Antibody recognition of cathepsin L1-derived peptides in Fasciola hepatica
      infected and/or vaccinated cattle and identification of protective linear B-cell
      epitopes.
AB  - Fasciola hepatica infection causes important economic losses in livestock and
      food industries around the world. In the Republic of Ireland F. hepatica
      infection has an 76% prevalence in cattle. Due to the increase of anti-helminthic
      resistance, a vaccine-based approach to control of Fasciolosis is urgently
      needed. A recombinant version of the cysteine protease cathepsin L1 (rmFhCL1)
      from F. hepatica has been a vaccine candidate for many years. We have found that
      vaccination of cattle with this immunodominant antigen has provided protection
      against infection in some experimental trials, but not in others. Differential
      epitope recognition between animals could be a source of variable levels of
      vaccine protection. Therefore, we have characterised for first time linear B-cell
      epitopes recognised within the FhCL1 protein using sera from F. hepatica-infected
      and/or vaccinated cattle from two independent trials. Results showed that all F.
      hepatica infected animals recognised the region 19-31 of FhCL1, which is situated
      in the N-terminal part of the pro-peptide. Vaccinated animals that showed fluke
      burden reduction elicited antibodies that bound to the regions 120-137, 145-155,
      161-171 of FhCL1, which were not recognised by non-protected animals. This data,
      together with the high production of specific IgG2 in animals showing vaccine
      efficacy, suggest important targets for vaccine development.

PMID- 29373192
TI  - The cost-effectiveness of trivalent and quadrivalent influenza vaccination in
      communities in South Africa, Vietnam and Australia.
AB  - BACKGROUND: To inform national healthcare authorities whether quadrivalent
      influenza vaccines (QIVs) provide better value for money than trivalent influenza
      vaccines (TIVs), we assessed the cost-effectiveness of TIV and QIV in low-and
      middle income communities based in South Africa and Vietnam and contrasted these
      findings with those from a high-income community in Australia. METHODS:
      Individual based dynamic simulation models were interfaced with a health economic
      analysis model to estimate the cost-effectiveness of vaccinating 15% of the
      population with QIV or TIV in each community over the period 2003-2013.
      Vaccination was prioritized for HIV-infected individuals, before elderly aged 65+
      years and young children. Country or region-specific data on influenza-strain
      circulation, clinical outcomes and costs were obtained from published sources.
      The societal perspective was used and outcomes were expressed in International$
      (I$) per quality-adjusted life-year (QALY) gained. RESULTS: When compared with
      TIV, we found that QIV would provide a greater reduction in influenza-related
      morbidity in communities in South Africa and Vietnam as compared with Australia.
      The incremental cost-effectiveness ratio of QIV versus TIV was estimated at
      I$4183/QALY in South Africa, I$1505/QALY in Vietnam and I$80,966/QALY in
      Australia. CONCLUSIONS: The cost-effectiveness of QIV varied between communities
      due to differences in influenza epidemiology, comorbidities, and unit costs.
      Whether TIV or QIV is the most cost-effective alternative heavily depends on
      influenza B burden among subpopulations targeted forvaccination in addition to
      country-specific willingness-to-pay thresholds and budgetary impact.

PMID- 29373194
TI  - A simple clinical method for predicting the benefit of prone vs. supine
      positioning in reducing heart exposure during left breast radiotherapy.
AB  - BACKGROUND AND PURPOSE: The benefit of reduced radiation heart exposure in the
      prone vs. supine position individually differs. In this prospective cohort study,
      the goal was to develop a simple method for the operation of a validated model
      for the prediction of preferable treatment position during left breast
      radiotherapy. MATERIAL AND METHODS: In 100 cases, a single CT slice was utilized
      for the collection of the needed patient-specific data (in addition to body mass
      index, the distance of the LAD from the chest wall and the area of the heart
      included in the radiation fields at the middle of the heart in the supine
      position). Outcome was analyzed in relation to the full CT series acquired in
      both positions and dosimetric data. RESULTS: Great consistency was found between
      the tested and original method regarding sensitivity and specificity. The
      prioritization of LAD dose, and the use of heart dose and position-specific dose
      constraints as safety measures ensure sensitivity and specificity values of 82.8%
      and 87.3%, respectively. In an additional "routine clinical practice" series of
      60 patients the new method seemed feasible in routine clinical practice. External
      testing on a 28-case series indicated similar accuracy. CONCLUSION: We consider
      this simple clinical tool appropriate for assisting individual positioning aiming
      at maximum heart protection during left breast irradiation.

PMID- 29373195
TI  - Ototoxicity and cochlear sparing in children with medulloblastoma: Proton vs.
      photon radiotherapy.
AB  - PURPOSE: To compare ototoxicity rates between medulloblastoma patients treated
      with protons vs. photons. MATERIALS AND METHODS: The study included 84 children
      diagnosed with medulloblastoma treated with either passively scattered protons (n
      = 38) or photons (n = 46). Patients underwent maximal safe resection followed by
      craniospinal irradiation, posterior fossa and/or tumor bed boost and chemotherapy
      according to one of 3 multi-institutional trials. Median audiogram follow-up was
      56 months for protons and 66 months for photons. RESULTS: Mean cochlear dose
      (Dmc) was lower in patients treated with protons for both standard (p < 0.0001)
      and high-risk disease (p < 0.001). Grade 3 and 4 ototoxicity was seen in 7 of 75
      (9.3%) and 9 of 91 (9.9%) ears (Brock, p = 0.91), 13 of 75 (17.3%) and 19 of 91
      (20.9%) ears (POG, p = 0.56), and 15 of 75 (20.0%) and 21 of 91 (23.1%) ears
      (SIOP Boston, p = 0.63) with protons and photons respectively. CONCLUSIONS: While
      cochlear doses were lower in the proton group, patients treated with either
      protons or photons had similar Grade 3 and 4 ototoxicity rates.

PMID- 29373196
TI  - Treatment outcome and prognostic factors for adult patients with medulloblastoma:
      The Rare Cancer Network (RCN) experience.
AB  - BACKGROUND AND PURPOSE: The optimal treatment for adults with newly diagnosed
      medulloblastoma (MB) has not been defined. We report a large series of cases from
      the Rare Cancer Network. MATERIAL AND METHODS: Thirteen institutions enrolled 206
      MB patients who underwent postoperative radiotherapy (RT) between 1976 and 2014.
      Log-rank univariate and Cox-modeled multivariate analyses were used to analyze
      data collected. RESULTS: Median patient age was 29 years; follow-up was 31
      months. All patients had the tumor resected; surgery was complete in 140 (68%)
      patients. Postoperative RT was given in 202 (98%) patients, and 94% received
      craniospinal irradiation (CSI) and, usually, a posterior fossa boost. Ninety
      eight (48%) patients had chemotherapy, mostly cisplatin and vincristine-based.
      The 10-year local control, overall survival, and disease-free survival rates were
      46%, 51%, and 38%, respectively. In multivariate analyses, Karnofsky Performance
      Status (KPS) >=80 and CSI were significant for disease-free and overall survival
      (P <= .04 for all); receiving chemotherapy and KPS >=80 correlated with better
      local-control rates. CONCLUSIONS: Patients with high KPS who received CSI had
      better rates of disease-free and overall survival. Chemotherapy was associated
      with better local control. These results may serve as a benchmark for future
      studies designed to improve outcomes for adults with medulloblastoma.

PMID- 29373197
TI  - The role of inflammatory cytokines and tumor associated macrophages (TAMs) in
      microenvironment of pancreatic cancer.
AB  - Pancreatic cancer is considered as one of the most lethal types of cancer due to
      its poor prognosis and lack of effective therapeutic approaches. Although many
      studies have been done on pancreatic cancer, the current treatment methods did
      not exhibit successful results. Hence, novel strategies are needed for treatment
      of pancreatic cancer. The microenvironment of pancreatic cancer contains many
      factors such as inflammatory cytokines and tumor associated macrophages (TAMs),
      which influence the tumor's status. These factors can be upregulated and
      consequently lead to exacerbation of tumor progression. Understanding the role of
      pro- and anti-inflammatory cytokines and the function of TAMs in the pancreatic
      cancer microenvironment might lead to development and improvement of novel
      strategies in the diagnosis and treatment of pancreatic cancer and may result in
      promising treatments for this type of cancer.

PMID- 29373199
TI  - Facial morphology and growth following surgery for congenital midline cervical
      cleft patients.
AB  - Congenital midline cervical cleft (CMCC) is a rare condition that consists of a
      cutaneous midline neck lesion with a sinus extending inferiorly towards the
      sternum. A fibrous band that extends superiorly to the mandible is a consistent
      feature of the condition. Restriction of growth of the mandible, possibly due to
      incomplete removal of the band, is the most significant long-term problem. It
      remains unclear whether early removal of the fibrous band might allow catch-up
      growth of the mandible. This study utilized non-invasive three-dimensional
      photographs to objectively evaluate the facial growth of six CMCC patients. The
      growth of these CMCC patients was compared to the average growth of age- and sex
      matched controls from a database of three-dimensional facial photographs of
      clinically normal subjects. After surgical removal of the fibrous cord, CMCC
      patients experience growth in the chin at the same rate as in the normal
      population; no evidence was found for catch-up growth. As a result, individuals
      with CMCC are likely to require further surgical intervention to correct the
      residual retrognathia on completion of facial growth. Early excision of the
      lesion including aggressive resection of the fibrous band is still recommended,
      as this should optimize the early growth of the mandible in infancy.

PMID- 29373200
TI  - Survey of patient experiences of orthognathic surgery: health-related quality of
      life and satisfaction.
AB  - The objective of this study was to assess changes in patient quality of life
      (QoL) after orthognathic surgery at the Kuwait University Dental Clinic. A self
      administered Arabic version of the Orthognathic Quality of Life Questionnaire
      (OQLQ) and two different visual analogue scales (VAS) were used. Sixty-six
      patients participated (63.6% female). The deformities were corrected by
      bimaxillary jaw surgery (83.3%), Le Fort I (9.1%), and bilateral sagittal split
      osteotomy (7.6%). The most important reasons given for undertaking the surgery
      were facial aesthetics (80.3%) and bite correction (75.8%). Of the patients who
      had reported moderate to high levels of problems pre-surgery, the majority
      reported improvements in facial appearance (91.3%), appearance of the teeth
      (97.0%), biting (96.3%), chewing (92.3%), and eating function (76.5%). Overall,
      93.9% of patients reported better conditions after surgery, and the satisfaction
      level was very high (VAS 91.6%). The VAS score for QoL increased significantly
      from pre-surgery (73.0%) to post-surgery (93.6%) (P=0.0001). The OQLQ score was
      also significantly decreased after surgery, reflecting improvements in the
      'social aspects of dentofacial deformity', 'facial aesthetics', 'oral function',
      and 'awareness of dentofacial aesthetics' domains (P=0.0001). Overall, the
      patients who underwent orthognathic surgery were satisfied and had improved QoL.
      The satisfaction rate in the present study reflects successful treatment with
      orthognathic surgery.

PMID- 29373198
TI  - Lineage specification in innate lymphocytes.
AB  - Innate lymphoid cells (ILCs) are immune cells that lack specific antigen
      receptors but possess similar effector functions as T cells. Concordantly, ILCs
      express many transcription factors known to be important for T cell effector
      function. ILCs develop from lymphoid progenitors in fetal liver and adult bone
      marrow. However, the identification of ILC progenitor (ILCP) and other precursors
      in peripheral tissues raises the question of whether ILC development might occur
      at extramedullary sites. We discuss central and local generation in maintaining
      ILC abundance at peripheral sites.

PMID- 29373201
TI  - Small size of metastatic lymph nodes with extracapsular spread greatly impacts
      treatment outcomes in oral squamous cell carcinoma patients.
AB  - Extracapsular spread (ECS) of metastatic lymph nodes from oral carcinoma is the
      most significant prognostic predictor of a poor treatment outcome. However, only
      a few reports on prognostic factors in ECS-positive cases have been investigated.
      To address this problem, a detailed examination of ECS pathology was conducted to
      determine the prognostic factors of oral squamous cell carcinoma (OSCC) with ECS
      of metastatic lymph nodes. This study involved 63 OSCC patients with at least one
      pathologically metastatic node with ECS. Among the 229 metastatic lymph nodes,
      149 exhibited ECS. Univariate analysis revealed that a poor outcome and
      recurrence were significantly associated with the number of ECS-positive nodes,
      density of ECS, and the minor axis of the smallest ECS-positive node. However,
      multivariate analysis identified only small size of ECS-positive nodes as a
      significant and independent factor predicting recurrence and a poor outcome.
      Thus, small size of ECS-positive nodes is the most important prognostic indicator
      for OSCC with ECS in metastatic lymph nodes. The classification of ECS status
      using the minor axis of ECS-positive nodes may be useful for further prediction
      of a poorer prognosis in OSCC cases. Standardization of ECS diagnosis and
      multicenter prospective studies will be required to confirm and refine these
      findings.

PMID- 29373202
TI  - Reconstruction of the mandibular condyle using the microvascular lateral femoral
      condyle flap.
AB  - The lateral femoral condyle (LFC) flap is a new flap first reported in 2015 for
      the treatment of osteomyelitis in hand surgery. This paper introduces a technique
      of osteochondral LFC flap harvest for mandibular condyle reconstruction and
      reports on the use of this flap in temporomandibular joint reconstruction. For
      condyle resection, a pre-auricular approach saving the temporal artery and vein
      is performed. A step osteotomy technique is used for condyle resection. LFC
      harvesting starts with dissection of the popliteal artery and vein. The superior
      genicular artery and vein are identified and followed along their periosteal
      branches. An osteochondral flap according to the condyle defect is harvested from
      the anterior pole of the knee. The flap is banded according to the defect and
      fixed to the mandibular neck with three miniscrews. Follow-up computed tomography
      scans should be performed at 1 week, 6 months, and 1year after surgery. The case
      of a 58-year-old female patient with osteomyelitis of the left mandibular condyle
      after multiple preoperative therapies is reported. The LFC flap technique was
      used for left condyle reconstruction, resulting in good functional and
      morphological outcomes at the 6-month postoperative follow-up. In conclusion, the
      osteochondral LFC flap is a new and promising technique for mandibular condyle
      reconstruction for special indications.

PMID- 29373203
TI  - Editor's Choice - A Prospective Study to Evaluate Complete Wound Healing and Limb
      Salvage Rates After Angiosome Targeted Infrapopliteal Balloon Angioplasty in
      Patients with Critical Limb Ischaemia.
AB  - OBJECTIVE/BACKGROUND: To evaluate complete wound healing and limb salvage rates
      in patients with critical limb ischaemia (CLI) with concurrent foot
      ulceration/gangrene who underwent angiosome targeted infrapopliteal balloon
      angioplasty. METHODS: This was a prospective observational study. In total, 212
      patients who underwent successful infrapopliteal balloon angioplasty to assist
      wound healing and achieve limb salvage were included from June 2014 to March
      2016. Propensity score matching was developed to compare complete wound healing,
      1 year amputation free survival (AFS), and limb salvage rates between the two
      study groups (direct revascularisation [DR] and indirect revascularisation [IR]).
      RESULTS: Direct flow to the foot wounds based on the angiosome principle was
      achieved in 117 legs (55.2%) versus 95 legs (44.8%) that represented the IR
      group. Seventy-three matched pairs were obtained to minimise intergroup
      differences in baseline characteristics. Twelve months after angioplasty, the
      complete wound healing rates were 80.8% and 63.0% (p = .02), AFS rates were 72.6%
      and 61.6% (p = .164), and limb salvage rates were 90.4% and 82.2% (p = .148) in
      the DR and IR groups, respectively. CONCLUSION: This study suggests that the
      complete wound healing rate is better when the target foot lesion receives direct
      perfusion following the angiosome concept, whereas limb salvage and AFS rates
      were not significantly different among the DR and IR groups.

PMID- 29373204
TI  - Trends in physical activity, health-related fitness, and gross motor skills in
      children during a two-year comprehensive school physical activity program.
AB  - OBJECTIVES: The purpose of this study was to examine the trends in school-day
      step counts, health-related fitness, and gross motor skills during a two-year
      Comprehensive School Physical Activity Program (CSPAP) in children. DESIGN:
      Longitudinal trend analysis. METHODS: Participants were a sample of children
      (N=240; mean age=7.9+/-1.2 years; 125 girls, 115 boys) enrolled in five low
      income schools. Outcome variables consisted of school day step counts, Body Mass
      Index (BMI), estimated VO2 Peak, and gross motor skill scores assessed using the
      Test of Gross Motor Development-3rd Edition (TGMD-3). Measures were collected
      over a two-year CSPAP including a baseline and several follow-up time-points.
      Multi-level mixed effects models were employed to examine time trends on each
      continuous outcome variable. Markov-chain transition models were employed to
      examine time trends for derived binary variables for school day steps, BMI, and
      estimated VO2 Peak. RESULTS: There were statistically significant time
      coefficients for estimated VO2 Peak (b=1.10mL/kg/min, 95% C.I. [0.35mL/kg/min
      2.53mL/kg/min], p=0.009) and TGMD-3 scores (b=7.8, 95% C.I. [6.2-9.3], p<0.001).
      There were no significant changes over time for school-day step counts or BMI.
      Boys had greater change in odds of achieving a step count associating with 30min
      of school day MVPA (OR=1.25, 95% C.I. [1.02-1.48], p=0.044). CONCLUSIONS: A two
      year CSPAP related to increases in cardio-respiratory endurance and TGMD-3
      scores. School day steps and BMI were primarily stable across the two-year
      intervention.

PMID- 29373205
TI  - A 20*20m repeated sprint field test replicates the demands of wheelchair rugby.
AB  - OBJECTIVES: To assess the physiological responses to, and the agreement between,
      a 20*20m repeated sprint field test and wheelchair rugby game play, as well as
      the reliability of the test. DESIGN: Cross-sectional and longitudinal. METHODS:
      Heart rate (HR), blood lactate ([La-]B), and ratings of perceived exertion (RPE)
      were collected in nineteen elite wheelchair rugby athletes before, during, and
      after a 20*20m repeated sprint field test and game play. Times to complete 5, 10,
      and 20m during the field test were also collected. RESULTS: Peak HR and peak [La
      ]B were positively correlated during the field test (r=0.470, p=0.043), as were
      peak HR and peak speed (r=0.493, p=0.031), and peak [La-]B and peak speed
      (r=0.559, p=0.013). During game play, peak [La-]B was correlated with peak RPE
      (rho=0.703, p=0.001). Intra-class correlations (ICCs) between the field test and
      game play were significant for peak HR (ICC=0.922, p<0.001) and peak [La-]B
      (ICC=0.845, p<0.001). Bland-Altman analysis revealed good agreement between HR
      and [La-]B obtained during the field test and game play and excellent between-day
      reliability of the 20*20m sprint test. CONCLUSIONS: The physiological demands of
      a 20*20m repeated sprint field test are similar to those of elite wheelchair
      rugby game play and the test is highly reliable. This simple to implement field
      test may be useful as a component of team selection and in assessing the
      effectiveness of training interventions or monitoring athletes across training
      phases.

PMID- 29373206
TI  - Aggressive ossifying fibroma of right ethmoidal sinus: A case report.
AB  - BACKGROUND: Ossifying fibroma is a rare benign fibro-osseous lesion seen in the
      bones of the head and neck area. It is mostly found in the mandible followed by
      the maxilla and rarely in the paranasal sinuses along with the orbit and skull
      bones. CASE PRESENTATION: A 30-year-old male patient presented with headache and
      incidental finding of a right ethmoidal sinus ossifying fibroma by paranasal
      sinuses CT scan and MRI of the face. A flexible fiber-optic nasal endoscopy
      examination revealed a right side fullness. A non-contrasted CT scan of the
      paranasal sinus showed hyperdense lesion at the right ethmoid air cells.
      Functional endoscopic sinus surgery was performed and multiple nasal-mass
      biopsies were taken which showed fibro-osseous lesion most consistent with
      aggressive ossifying fibroma. Later, a near total resection of skull base tumor
      by endoscopic surgery was done and patient was discharged next day in a good
      condition. CONCLUSION: Ossifying fibroma is a rare lesion found in the head and
      neck area and it is unusual to be found in the paranasal sinuses. Thus crucial
      attention to the clinical, radiographical and histopathological examination
      should be taken for more accurate diagnosis and thus appropriate management.

PMID- 29373207
TI  - Karakousis's abdominoinguinal approach for the treatment of a primary
      retroperitoneal parasitic leiomyoma with inguinal extension. A case report.
AB  - INTRODUCTION: Primary retroperitoneal parasitic leiomyoma (PRPL) with inguinal
      extension is a diagnostic-therapeutic challenge due to its uncertain
      etiopathogenesis and because it has been considered unresectable according to
      customary surgical techniques in some instances. The abdominoinguinal incision
      described by Karakousis in the 1980s allows a safe and radical approach for lower
      quadrants abdominopelvic tumors. OBJECTIVES: We present the case of a rare PRPL
      satisfactorily treated through Karakousis's approach. PRESENTATION OF CASE: A 35
      year-old woman was referred from the Gynecology Service to our Unit. She suffered
      from a pelvic tumor with left inguinal extension. Initially, it was diagnosed as
      a retroperitoneal sarcomatous tumor as any digestive and/or gynecological origins
      of the pelvic tumor were excluded. A radical oncologic excision with permanent
      neuro-vascular control was undertaken using a left Karakousis's abdominoinguinal
      approach. The final anatomopathological report was PRPL. The patient was
      discharged after 8 days. She is disease-free 18 months later. DISCUSSION: PRPL
      variant could be related to remnant embryogenic cells of the ducts of Wolf and
      Muller. Karakousis's approach allowed an en-bloc ilioinguinal removal of the
      tumor in continuity, with permanent control of the aorto-ileo-femoral axis, the
      sparing of the neuro-vascular package, and ensured a total abdominal wall
      restoration. CONCLUSIONS: PRPL is a rare extrauterine entity probably derived
      from remnant embryogenic cells. The absence of clinical guidelines recommend an
      individualized treatment of these patients. Karakousis's abdominoinguinal
      approach should be present in any surgeon's armamentarium as the resectability
      rate of tumors of the lower quadrant of the abdomen increases up to 95%.

PMID- 29373208
TI  - Predictors of Shunt Dysfunction and Overall Survival in Patients with Variceal
      Bleeding Treated with Transjugular Portosystemic Shunt Creation Using the Fluency
      Stent Graft.
AB  - RATIONALE AND OBJECTIVES: Transjugular intrahepatic portosystemic shunt (TIPS) is
      an established method for portal hypertension. This study was to investigate the
      long-term safety, technical success, and patency of TIPS, and to determine the
      risk factors and clinical impacts of shunt dysfunction. MATERIALS AND METHODS: A
      total of 154 consecutive patients undergoing embolotherapy of gastric coronary
      vein and/or short gastric vein and TIPS creation were prospectively studied.
      Follow-up data included technical success, patency and revision of TIPS, and
      overall survival of patients. RESULTS: During the study, the primary and
      secondary technical success rates were 98.7% and 100%, respectively. Sixty-three
      patients developed shunt dysfunction, 30 with shunt stenosis and 33 with shunt
      occlusion. The cumulative 60-month primary, primary assisted, and secondary
      patency rates were 19.6%, 43.0%, and 93.4%, respectively. The cumulative 60-month
      overall survival rates were similar between the TIPS dysfunction group and the
      TIPS non-dysfunction group (68.6% vs. 58.6%, P = .096). Baseline portal vein
      thrombosis (P < .001), use of bare stents (P = .018), and portal pressure
      gradient (PPG) (P = .020) were independent predictors for shunt dysfunction,
      hepatocellular carcinoma (P < .001), and ascites (P = .003) for overall survival.
      The accuracy of PPG for shunt dysfunction was statistically significant (P <
      .001), and a cutoff value of 8.5 had 77.8% sensitivity and 64.8% specificity.
      CONCLUSIONS: The long-term safety, technical success, and patency of TIPS were
      good; baseline portal vein thrombosis, use of bare stents, and PPG were
      significantly associated with shunt dysfunction; shunt dysfunction has little
      impact on patients' long-term survival because of high secondary patency rates.

PMID- 29373209
TI  - Automated Radiology-Pathology Module Correlation Using a Novel Report Matching
      Algorithm by Organ System.
AB  - OBJECTIVES AND RATIONALE: Radiology-pathology correlation is time-consuming and
      is not feasible in most clinical settings, with the notable exception of breast
      imaging. The purpose of this study was to determine if an automated radiology
      pathology report pairing system could accurately match radiology and pathology
      reports, thus creating a feedback loop allowing for more frequent and timely
      radiology-pathology correlation. METHODS: An experienced radiologist created a
      matching matrix of radiology and pathology reports. These matching rules were
      then exported to a novel comprehensive radiology-pathology module. All distinct
      radiology-pathology pairings at our institution from January 1, 2016 to July 1,
      2016 were included (n = 8999). The appropriateness of each radiology-pathology
      report pairing was scored as either "correlative" or "non-correlative." Pathology
      reports relating to anatomy imaged in the specific imaging study were deemed
      correlative, whereas pathology reports describing anatomy not imaged with the
      particular study were denoted non-correlative. RESULTS: Overall, there was 88.3%
      correlation (accuracy) of the radiology and pathology reports (n = 8999). Subset
      analysis demonstrated that computed tomography (CT) abdomen/pelvis, CT
      head/neck/face, CT chest, musculoskeletal CT (excluding spine), mammography,
      magnetic resonance imaging (MRI) abdomen/pelvis, MRI brain, musculoskeletal MRI
      (excluding spine), breast MRI, positron emission tomography (PET), breast
      ultrasound, and head/neck ultrasound all demonstrated greater than 91%
      correlation. When further stratified by imaging modality, CT, MRI, mammography,
      and PET demonstrated excellent correlation (greater than 96.3%). Ultrasound and
      non-PET nuclear medicine studies demonstrated poorer correlation (80%).
      CONCLUSION: There is excellent correlation of radiology imaging reports and
      appropriate pathology reports when matched by organ system. Rapid, appropriate
      radiology-pathology report pairings provide an excellent opportunity to close
      feedback loop to the interpreting radiologist.

PMID- 29373210
TI  - Discriminating Depth of Response to Therapy in Multiple Myeloma Using Whole-body
      Diffusion-weighted MRI with Apparent Diffusion Coefficient: Preliminary Results
      From a Single-center Study.
AB  - RATIONALE AND OBJECTIVES: This study aimed to measure apparent diffusion
      coefficient (ADC) in Chinese patients with newly diagnosed multiple myeloma by
      whole-body diffusion-weighted magnetic resonance imaging (WB-DWI MRI) and assess
      the diagnostic accuracy of ADC in the discrimination of deep response to
      induction chemotherapy. MATERIALS AND METHODS: Seventeen patients underwent WB
      DWI MRI before and after induction chemotherapy (week 20). DWI images and ADC
      maps were produced and 89 regions of interest were chosen. ADC percent changes
      were compared between deep (complete response or very good partial response) and
      non-deep responders (partial response, minimal response, stable disease, or
      progressive disease) as International Myeloma Working Group criteria. Diagnostic
      accuracy of ADC was calculated using specific cut offs. Predictive positive value
      of ADC was calculated to predict deep response to consolidation therapy. RESULTS:
      Lesions reduced in size and number and signal intensity decreased in follow-up
      DWI, which did not differ between deep and non-deep responders. ADC percent
      changes were significantly higher in deep responders (36.79%) than in non-deep
      responders (11.50%) after induction therapy (P = .02) in per lesion analysis. ADC
      percent increases by 46.96%, 78.0% yielded specificity at 81.4%, 90.7% in
      discriminating deep response to induction therapy. Predictive positive value
      predicting deep response to consolidation therapy was 60.5% by using ADC cutoff
      >1.00 * 10-3 mm2/s at week 20. CONCLUSIONS: ADC from WB-DWI MRI increased
      remarkably in patients who achieved deep response at the end of induction
      chemotherapy, which represented a confirmatory diagnostic tool to discriminate
      deep response to induction therapy for patients with multiple myeloma. ADC may
      have a potential to predict deep response to consolidation therapy.

PMID- 29373211
TI  - Effect of Matrix Size on the Image Quality of Ultra-high-resolution CT of the
      Lung: Comparison of 512 * 512, 1024 * 1024, and 2048 * 2048.
AB  - RATIONALE AND OBJECTIVES: This study aimed to assess the effect of matrix size on
      the spatial resolution and image quality of ultra-high-resolution computed
      tomography (U-HRCT). MATERIALS AND METHODS: Slit phantoms and 11 cadaveric lungs
      were scanned on U-HRCT. Slit phantom scans were reconstructed using a 20-mm field
      of view (FOV) with 1024 matrix size and a 320-mm FOV with 512, 1024, and 2048
      matrix sizes. Cadaveric lung scans were reconstructed using 512, 1024, and 2048
      matrix sizes. Three observers subjectively scored the images on a three-point
      scale (1 = worst, 3 = best), in terms of overall image quality, noise, streak
      artifact, vessel, bronchi, and image findings. The median score of the three
      observers was evaluated by Wilcoxon signed-rank test with Bonferroni correction.
      Noise was measured quantitatively and evaluated with the Tukey test. A P value of
      <.05 was considered significant. RESULTS: The maximum spatial resolution was 0.14
      mm; among the 320-mm FOV images, the 2048 matrix had the highest resolution and
      was significantly better than the 1024 matrix in terms of overall quality, solid
      nodule, ground-glass opacity, emphysema, intralobular reticulation, honeycombing,
      and clarity of vessels (P < .05). Both the 2048 and 1024 matrices performed
      significantly better than the 512 matrix (P < .001), except for noise and streak
      artifact. The visual and quantitative noise decreased significantly in the order
      of 512, 1024, and 2048 (P < .001). CONCLUSION: In U-HRCT scans, a large matrix
      size maintained the spatial resolution and improved the image quality and
      assessment of lung diseases, despite an increase in image noise, when compared to
      a 512 matrix size.

PMID- 29373212
TI  - Associations of County-level Radiologist and Mammography Facility Supply with
      Screening Mammography Rates in the United States.
AB  - RATIONALE AND OBJECTIVES: The present study aims to assess associations of
      Medicare beneficiary screening mammography rates with local mammography facility
      and radiologist availability. MATERIALS AND METHODS: Mammography screening rates
      for Medicare fee-for-service beneficiaries were obtained for US counties using
      the County Health Rankings data set. County-level certified mammography facility
      counts were obtained from the United States Food and Drug Administration. County
      level mammogram-interpreting radiologist and breast imaging subspecialist counts
      were determined using Centers for Medicare & Medicaid Services fee-for-service
      claims files. Spearman correlations and multivariable linear regressions were
      performed using counties' facility and radiologist counts, as well as counts
      normalized to counties' Medicare fee-for-service beneficiary volume and land
      area. RESULTS: Across 3035 included counties, average screening mammography rates
      were 60.5% +/- 8.2% (range 26%-88%). Correlations between county-level screening
      rates and total mammography facilities, facilities per 100,000 square mile county
      area, total mammography-interpreting radiologists, and mammography-interpreting
      radiologists per 100,000 county-level Medicare beneficiaries were all weak (r =
      0.22-0.26). Correlations between county-level screening rates and mammography
      rates per 100,000 Medicare beneficiaries, total breast imaging subspecialist
      radiologists, and breast imaging subspecialist radiologists per 100,000 Medicare
      beneficiaries were all minimal (r = 0.06-0.16). Multivariable analyses overall
      demonstrated radiologist supply to have a stronger independent effect than
      facility supply, although effect sizes remained weak for both. CONCLUSION:
      Mammography facility and radiologist supply-side factors are only weakly
      associated with county-level Medicare beneficiary screening mammography rates,
      and as such, screening mammography may differ from many other health-care
      services. Although efforts to enhance facility and radiologist supply may be
      helpful, initiatives to improve screening mammography rates should focus more on
      demand-side factors, such as patient education and primary care physician
      education and access.

PMID- 29373214
TI  - Early Androgen Deprivation Therapy Improves Survival, But How Do We Determine in
      Whom?

PMID- 29373213
TI  - Does Second Reader Opinion Affect Patient Management in Pancreatic Ductal
      Adenocarcinoma?
AB  - RATIONALE AND OBJECTIVES: To determine the impact of second-opinion assessment on
      cancer staging and patient management in patients with pancreatic ductal
      adenocarcinoma. METHODS AND MATERIALS: This retrospective study was approved by
      our institutional review board with a waiver of informed consent. Second-opinion
      reports between January 1, 2009 and December 31, 2013, alongside outside reports
      for 65 consecutive cases of biopsy-proven pancreatic adenocarcinomas, were
      presented in random order to two experienced abdominal surgeons who independently
      reviewed them blinded to the origin of the report, images of the examinations,
      and patient identifier. Each surgeon filled in a questionnaire for each report
      recommending cancer staging and patient management. Recommended patient
      management and staging were evaluated against reference standards (actual patient
      management at 6 months following second-opinion assessment, and pathology or
      other clinical and imaging reference standards at 6 months or longer,
      respectively) using Cohen kappa. RESULTS: Cancer staging differed in 13% (9 of
      65) of cases for surgeon 1 and in 18.4% (12 of 65) for surgeon 2. Patient
      management changed in 38.4% (25 of 65) of cases for surgeon 1 and in 20% (13 of
      65) for surgeon 2. When compared to the pathologic staging gold standard, second
      opinion was correct in 85.7% (six of seven) of the time for both surgeons.
      Recommended patient management from second-opinion reports showed good agreement
      with the reference standard (weighted k = 0.6467 [0.4014-0.892] and weighted k =
      0.6262 [0.3954-0.857] for surgeon 2). CONCLUSION: Second-opinion review by
      subspecialized oncologic radiologists can impact patient care, specifically in
      terms of management decision.

PMID- 29373215
TI  - Focal Therapy in Primary Localised Prostate Cancer: The European Association of
      Urology Position in 2018.
AB  - : Radical treatment of localised prostate cancer is recognised to be an
      unnecessary intervention or overtreatment in many men. Consequently, there has
      been a rapid uptake in the use of focal ablative therapies. However, there are
      several biological and practical concerns about such approaches as they have yet
      to be proved as robust treatment options. In particular, the multifocal nature of
      prostate cancer argues against unifocal treatment, while limitations in imaging
      can preclude the accurate identification of the number, location, and extent of
      prostate cancer foci. To date, a number of ablative options have reported results
      on mainly low-risk disease. Most series are relatively immature, with a lack of
      consistent follow-up, and the morbidity of retreatment is often not considered.
      The authors consider focal therapy to be an investigational modality, and
      encourage prospective recording of outcomes and recruitment of suitable patients.
      PATIENT SUMMARY: Focal therapy of prostate cancer is the targeted destruction of
      cancer within a specific part of the prostate gland, sparing the rest of the
      prostate and nearby tissue. This procedure could potentially reduce side effects
      when compared with established standard treatments, such as surgery or
      radiotherapy, which treat the entire prostate. Studies show that for most men
      with low-risk cancer, active surveillance is the preferred treatment option.
      However, the available data regarding all forms of focal therapy are still poor
      and inconclusive. Consequently, due to both the lack of clear results associated
      with focal therapy and the difficulties in detecting all cancerous areas of the
      prostate, focal therapy should be considered an investigational modality only.

PMID- 29373216
TI  - An Update on Fatalities Due to Venomous and Nonvenomous Animals in the United
      States (2008-2015).
AB  - INTRODUCTION: To review recent (2008-2015) United States mortality data from
      deaths caused by nonvenomous and venomous animals and compare with historical
      data. METHODS: The Centers for Disease Control and Prevention Wide-Ranging Online
      Data for Epidemiologic Research database was queried to return all animal-related
      fatalities between 2008 and 2015. Mortality frequencies for animal-related
      fatalities were calculated using the estimated 2011 United States population.
      Inclusion criteria included all mortalities that were a consequence of bite,
      contact, attack, or envenomation (International Classification of Diseases 10th
      revision codes W53-W59 and X20-X29). RESULTS: There were 1610 animal-related
      fatalities, with the majority from nonvenomous animals (4.8 deaths per 10million
      persons annually). The largest proportion of animal-related fatalities was due to
      "other mammals," largely composed of horses and cattle. Deaths attributable to
      Hymenoptera (hornets, wasps, and bees) account for 29.7% of the overall animal
      related fatalities and have been steady over the last 20 years. Dog-related
      fatality frequencies are stable, although the fatality frequency of 4.6 deaths
      per 10 million persons among children 4 years of age or younger was nearly 4-fold
      greater than in the other age groups. CONCLUSIONS: Appropriate education and
      prevention measures aimed at decreasing injury from animals should be directed at
      the high-risk groups of agricultural workers and young children with dogs. Public
      policy and treatment pricing should align to ensure adequate available medication
      for those at risk of anaphylaxis from stings from Hymenoptera.

PMID- 29373217
TI  - An Effective Treatment in the Austere Environment? A Critical Appraisal into the
      Use of Intra-Articular Local Anesthetic to Facilitate Reduction in Acute Shoulder
      Dislocation.
AB  - Acute shoulder dislocation is a common injury in the outdoor environment. The
      objective of this systematic review of the literature was to determine if intra
      articular local anesthetic (IAL) is an effective treatment that could have
      prehospital application. A methodical search of MEDLINE, PubMed, and EMBASE
      databases targeted publications from January 1, 1990 until January 1, 2017.
      Eligible articles compared IAL with other analgesic techniques in patients 16
      years or older experiencing acute glenohumeral dislocation. Reduction success,
      complications, and patient-reported outcome measures underwent comparison. All
      identified publications originated from the hospital setting. Procedural success
      rates ranged widely among randomized control trials comparing IAL with
      intravenous analgesia and sedation (IAL 48-100%, intravenous analgesia and
      sedation 44-100%). A pooled risk ratio [RR] favored intravenous analgesia and
      sedation (RR 0.91, 95% confidence interval [CI] 0.84-0.98), but there was
      significant inconsistency within the analysis (I2 = 75%). IAL provided lower
      complication rates (4/170, 2%) than intravenous analgesia and sedation (20/150,
      13%) (RR 1.11, 95% CI 1.04-1.19, I2 = 63%). One trial found a clinically relevant
      reduction in visual analogue pain scores when comparing IAL against no additional
      analgesia in the first minute (IAL 21+/-13 mm; control 49+/-15 mm; P<0.001) and
      fifth minute (IAL 10+/-10 mm; control 40+/-14 mm, P<0.001) after reduction. The
      results suggest that IAL is an effective intervention for acute anterior shoulder
      dislocation that would have a place in the repertoire of the remote physician.
      Further research might be beneficial in determining the outcomes of performing
      IAL in the prehospital setting.

PMID- 29373219
TI  - Cutaneous Vascular Responses of the Hands and Feet to Cooling, Rewarming, and
      Hypoxia in Humans.
AB  - INTRODUCTION: This study investigated skin vasomotor responses in the fingers and
      toes during cooling and rewarming with and without normobaric hypoxia. METHODS:
      Fourteen volunteers (8 males and 6 females) were exposed to gradual air cooling
      (mean+/-SD: -0.4+/-0.1oC.min-1) followed by rewarming (+0.5+/-0.1oC.min-1) while
      breathing normoxic air (FIO2 0.21 at 761+/-3 mm Hg) or hypoxic gas (FIO2 0.12, at
      761+/-3 mm Hg, equivalent to ~5000 m above sea level). Throughout the gradual
      cooling and rewarming phases, rectal temperature was measured, and skin
      temperatures and laser Doppler skin blood flow were measured on the thumb, little
      finger, and great and little toe pads. RESULTS: During gradual cooling, skin
      temperature but not deep body temperature decreased. No differences in cutaneous
      vascular conductance were found for the toes or thumb (P=0.169 great toe; P=0.289
      little toe; P=0.422 thumb). Cutaneous vascular conductance was reduced in the
      little finger to a greater extent at the same mean skin temperatures (34.5
      33.5oC) in the hypoxic compared with normoxic conditions (P=0.047). The onset of
      vasoconstriction and release of vasoconstriction in the thumb and little finger
      occurred at higher mean skin temperatures in hypoxia compared with normoxia
      (P<0.05). The onset of vasoconstriction and release of vasoconstriction in the
      toes occurred at similar skin temperatures (P=0.181 and P=0.132, respectively).
      CONCLUSION: The earlier vasoconstrictor response and later release of
      vasoconstriction in the finger during hypoxic conditions may result in a greater
      dose of cold to that digit, taking longer to rewarm following the release of
      vasoconstriction.

PMID- 29373220
TI  - Core Content for Wilderness Medicine Training: Development of a Wilderness
      Medicine Track Within an Emergency Medicine Residency.
AB  - Wilderness medicine training has become increasingly popular among medical
      professionals with numerous educational opportunities nationwide. Curricula for
      fellowship programs and for medical student education have previously been
      developed and published, but a specific curriculum for wilderness medicine
      education during emergency medicine (EM) residency has not. The objective of this
      study is to create a longitudinal wilderness medicine curriculum that can be
      incorporated into an EM residency program. Interest-specific tracks are becoming
      increasingly common in EM training. We chose this model to develop our curriculum
      specific to wilderness medicine. Outlined in the article is a 3-year longitudinal
      course of study that includes a core didactic curriculum and a plan for graduated
      level of responsibility. The core content is specifically related to the required
      EM core content for residency training with additions specific to wilderness
      medicine for the residents who pursue the track. The wilderness medicine
      curriculum would give residencies a framework that can be used to foster learning
      for residents interested in wilderness medicine. It would enhance the coverage of
      wilderness and environmental core content education for all EM residents in the
      program. It would provide wilderness-specific education and experience for
      interested residents, allowing them to align their residency program requirements
      through a focused area of study and enhancing their curriculum vitae at
      graduation. Finally, given the popularity of wilderness medicine, the presence of
      a wilderness medicine track may improve recruitment for the residency program.

PMID- 29373221
TI  - Reply to "Movement-related neural processing in people with congenital mirror
      movements beyond the (cortical) surface".

PMID- 29373222
TI  - Predicting contrast-induced nephropathy after percutaneous coronary intervention:
      Do we need formulas? A cardiological perspective.

PMID- 29373223
TI  - Factors associated with pulmonary dysfunction in patients undergoing coronary
      artery bypass graft surgery with use of intra-aortic balloon pump.
AB  - OBJECTIVE: The aim of this study was to identify pulmonary dysfunction and
      factors associated with prolonged mechanical ventilation, hospital stay, weaning
      failure and mortality in patients undergoing coronary artery bypass grafting with
      use of intra-aortic balloon pump (IABP). METHODS: This observational study
      analyzed respiratory, surgical, clinical and demographic variables and related
      them to outcomes. RESULTS: We analyzed 39 patients with a mean age of 61.2 years.
      Pulmonary dysfunction, characterized by mildly impaired gas exchange, was present
      from the immediate postoperative period to the third postoperative day.
      Mechanical ventilation time was influenced by the use of IABP and PaO2/FiO2,
      female gender and smoking. Intensive care unit (ICU) stay was influenced by
      APACHE II score and use of IABP. Mortality was strongly influenced by APACHE II
      score, followed by weaning failure. CONCLUSION: Pulmonary dysfunction was present
      from the first to the third postoperative day. Mechanical ventilation time was
      influenced by female gender, smoking, duration of IABP use and PaO2/FiO2 on the
      first postoperative day. ICU stay was influenced by APACHE II score and duration
      of IABP. Mortality was influenced by APACHE II score, followed by weaning
      failure.

PMID- 29373225
TI  - Response to Binar et al "Comment on 'Dysphagia and Obstructive Sleep Apnea in
      Acute, First-Ever, Ischemic Stroke'".

PMID- 29373224
TI  - Analysis of CDK2 mutations in Chinese men with non-obstructive azoospermia who
      underwent testis biopsy.
AB  - To examine whether mutations of the CDK2 gene exist in Chinese men with non
      obstructive azoospermia (NOA) with different histopathology, we recruited 175
      Chinese men with idiopathic NOA who underwent testis biopsy, including
      hypospermatogenesis, germ cell maturation arrest and Sertoli cell only syndrome.
      Genomic DNA was extracted from peripheral blood samples. Subsequently, the seven
      exons of the CDK2 gene were amplified using polymerase chain reaction with
      specific primers, respectively. The polymerase chain reaction products were
      sequenced on an automated sequencer. We identified four known single nucleotide
      polymorphisms: c.324G>A in exon 1; c.363T>C in exon 2; c.*570G>A; and c.*1160G>C
      in the 3' UTR of the CDK2 gene. Comparison of the genotype and allele frequencies
      showed no significant differences between NOA cases and controls for the four
      single nucleotide polymorphisms. Furthermore, no significant differences were
      found between each pathological group and control group, respectively. The
      results indicate that mutations in the coding sequence of the CDK2 gene may not
      be responsible for idiopathic NOA in Chinese men. Future studies in large cohorts
      of different ethnic populations are warranted to establish whether associations
      exist between the CDK2 gene and NOA.

PMID- 29373226
TI  - Multiple Cerebral Infarctions Due to Patent Foramen Ovale in a Patient with
      Eosinophilic Granulomatosis with Polyangiitis.
AB  - A 51-year-old man was diagnosed with eosinophilic granulomatosis with
      polyangiitis 6 years ago due to asthma, sinusitis, hypereosinophilia, and
      peripheral neuropathy based on the diagnostic criteria of American College of
      Rheumatology, and corticosteroid therapy achieved a remission. One year ago, he
      was hospitalized due to deep venous thrombosis (DVT) and pulmonary embolism, and
      rivaroxaban was administrated. He was admitted to our hospital for acute onset of
      diplopia and right hemiparesis. Peripheral blood examinations disclosed
      leukocytosis with hypereosinophilia. Perinuclear anti-neutrophil cytoplasmic
      antibodies were positive. Diffusion-weighted imaging showed multiple fresh
      ischemic lesions. Chronic ischemic lesions were seen in subcortical cerebral
      region. No stenosis or occlusion was shown in extracranial and intracranial
      arteries on magnetic resonance angiography. Ultrasonography of leg vein showed
      DVT. Right-to-left shunt through patent foramen ovale after Valsalva maneuver was
      seen on transesophageal echocardiography. Treatment with corticosteroid and
      cyclophosphamide alleviated clinical deterioration. Rivaroxaban was changed to
      warfarin. Diplopia and muscle strength of right limbs were improved. This is a
      first case of multiple cerebral infarction caused by paradoxical embolism due to
      patent foramen ovale with DVT based on hypercoagulable state of
      hypereosinophilia. Overall this case illustrates that eosinophilic granulomatosis
      with polyangiitis can be a risk factor for multiple cerebral infarction in the
      systemic phase and that transesophageal echocardiography and ultrasonography of
      leg vein should be conducted in stroke patient with eosinophilic granulomatosis
      with polyangiitis.

PMID- 29373227
TI  - Outcome of Acute Ischemic Stroke after the Treatment with Edaravone and 0.6 Mg/Kg
      Alteplase in Japanese Patients with Diabetes.
AB  - BACKGROUND: We investigated how diabetes mellitus (DM) affects the outcome of
      acute ischemic stroke (AIS), comparing with the outcomes in those who had
      hypertension (HT) and atrial fibrillation (AF). METHODS: This study was a sub
      analysis of PROTECT4.5, which was previously performed as a large-scale,
      prospective observational study of edaravone with approximately 10,000 patients
      with AIS in Japan. The study patients treated with edaravone alone or edaravone +
      alteplase (recombinant tissue plasminogen activator [tPA]) were analyzed for
      their outcomes and explored for the risk factors of poor outcome, after being
      divided into 8 groups according to their affected complications of DM, HT, or AF
      in the groups treated with edaravone alone or edaravone + tPA. RESULTS: Among
      patients treated with edaravone alone and edaravone + tPA, the mean reduction in
      the National Institutes of Health Stroke Scale from baseline to 3 months after
      the onset was 2.0 and 4.4 in DM groups, respectively. The reduction was smaller
      in these groups compared with other groups (3.3-4.3 and 6.0-7.7, respectively).
      The logistic regression model revealed that DM was an independent risk factor for
      highly unfavorable outcome of modified Rankin Scale score 3-6 at 3 months after
      the onset, among both patients treated with edaravone alone and those treated
      with edaravone + tPA (odds ratio [OR]: 2.23, 95% confidential interval [CI]: 1.42
      3.50 and OR: 2.05, 95% CI: 1.33-3.14, respectively). CONCLUSIONS: DM is suggested
      to adversely affect the outcome of AIS in Japanese patients.

PMID- 29373228
TI  - Effects of Early Mobilization after Acute Stroke: A Meta-Analysis of Randomized
      Control Trials.
AB  - BACKGROUND: Early mobilization is inconsistently associated with the recovery of
      stroke. We aim to examine the effect of early mobilization on patients with acute
      stroke. METHODS: PubMed, EMBASE, and the Cochrane library were searched up to
      April 2017. Randomized controlled trials that reported risk estimates or mean
      with standard deviation were included. Primary outcomes were defined as modified
      Rankin scale score 0-2 and mortality, and secondary outcomes were Barthel Index,
      length of stay, and incidence of complications. Summary relative risk,
      standardized mean difference (SMD), and weighted mean difference (WMD) were
      calculated as needed. Sensitivity analyses were also conducted to test stability
      of results. RESULTS: Six studies (8 publications) were included to analyze the
      effects of early mobilization after stroke. No differences between groups were
      observed for modified Rankin scale 0-2 (relative risk [RR]: .80; 95% confidence
      interval [CI]: .58-1.02; I2=45%) and the risk of death (RR: 1.21, 95% CI: .76
      1.65; I2=0%). Compared with conventional practice, early mobilization was
      superior in Barthel Index (SMD: .66; 95% CI: .00-1.31; I2=85.9%), and shorter
      hospital stay for stroke patients (WMD: -1.97; 95% CI: -2.63 to -1.32; I2=15.3%).
      We found no significant difference between groups on the incidence of
      complications. CONCLUSIONS: Current evidence revealed that no statistical
      significant difference between early mobilization and non-early mobilization was
      observed on modified Rankin scale score 0-2 and mortality. Interestingly, early
      mobilization is associated with an increased Barthel Index and shorter hospital
      stay for patients. Further research is necessary to verify the effect of early
      mobilization on patients with acute stroke.

PMID- 29373229
TI  - Comment on "Dysphagia and Obstructive Sleep Apnea in Acute, First-Ever, Ischemic
      Stroke".

PMID- 29373231
TI  - Automatic recognition of gait patterns in human motor disorders using machine
      learning: A review.
AB  - BACKGROUND: automatic recognition of human movement is an effective strategy to
      assess abnormal gait patterns. Machine learning approaches are mainly applied due
      to their ability to work with multidimensional nonlinear features. PURPOSE: to
      compare several machine learning algorithms employed for gait pattern recognition
      in motor disorders using discriminant features extracted from gait dynamics.
      Additionally, this work highlights procedures that improve gait recognition
      performance. METHODS: we conducted an electronic literature search on Web of
      Science, IEEE, and Scopus, using "human recognition", "gait patterns'', and
      "feature selection methods" as relevant keywords. RESULTS: analysis of the
      literature showed that kernel principal component analysis and genetic algorithms
      are efficient at reducing dimensional features due to their ability to process
      nonlinear data and converge to global optimum. Comparative analysis of machine
      learning performance showed that support vector machines (SVMs) exhibited higher
      accuracy and proper generalization for new instances. CONCLUSIONS: automatic
      recognition by combining dimensional data reduction, cross-validation and
      normalization techniques with SVMs may offer an objective and rapid tool for
      investigating the subject's clinical status. Future directions comprise the real
      time application of these tools to drive powered assistive devices in free-living
      conditions.

PMID- 29373232
TI  - An adaptive, real-time cadence algorithm for unconstrained sensor placement.
AB  - This paper evaluates a new and adaptive real-time cadence detection algorithm
      (CDA) for unconstrained sensor placement during walking and running. Conventional
      correlation procedures, dependent on sensor position and orientation, may
      alternately detect either steps or strides and consequently suffer from false
      negatives or positives. To overcome this limitation, the CDA validates
      correlation peaks as strides using the Sylvester's criterion (SC). This paper
      compares the CDA with conventional correlation methods. 22 volunteers completed 7
      different circuits (approx. 140 m) at three gaits-speeds: walking (1.5 m s-1),
      running (3.4 m s-1), and sprinting (5.2 and 5.7 m s-1), disturbed by various gait
      related activities. The algorithm was simultaneously evaluated for 10 different
      sensor positions. Reference strides were obtained from a foot sensor using a
      dedicated offline algorithm. The described algorithm resulted in consistent
      numbers of true positives (85.6-100.0%) and false positives (0.0-2.9%) and showed
      to be consistently accurate for cadence feedback across all circuits, subjects
      and sensors (mean +/- SD: 98.9 +/- 0.2%), compared to conventional cross
      correlation (87.3 +/- 13.5%), biased (73.0 +/- 16.2) and unbiased (82.2 +/- 20.6)
      autocorrelation procedures. This study shows that the SC significantly improves
      cadence detection, resulting in robust results for various gaits, subjects and
      sensor positions.

PMID- 29373230
TI  - Hyperperfusion after Clipping of Aneurysm: A Rare Entity.
AB  - BACKGROUND: Cerebral vasospasm is an uncontrollable and sometimes fatal
      complication occurring after subarachnoid hemorrhage. However, cerebral
      hyperperfusion syndrome is a rare complication after subarachnoid hemorrhage.
      Although plain computed tomography of cerebral hyperperfusion syndrome looks
      similar to cerebral infarction induced by cerebral vasospasm, they should be
      distinguished from each other because they require completely different
      treatments. CASE DESCRIPTION: A 65-year-old man complained of severe headache and
      vomiting. A computed tomography scan of his head showed subarachnoid hemorrhage
      with acute hydrocephalus caused by intraventricular hematoma and aneurysm of the
      left middle cerebral artery. After endoscopic irrigation of the ventricular
      hematoma to decrease the intracranial pressure, we performed neck clipping for
      the ruptured aneurysm. We used a temporary clip to the proximal M1 segment twice
      for a total of 15 minutes. Five days after the clipping, a computed tomography
      scan of the patient's head showed a large low-density area in the left cerebral
      hemisphere. Although cerebral infarction caused by cerebral vasospasm was
      suspected, his perfusion computed tomography demonstrated a state of
      hyperperfusion corresponding to the low-density area. We started treatment to
      prevent vasodilation and excessive cerebral blood flow instead of treatment for
      cerebral vasospasm. After changing the treatment, the patient's symptoms
      gradually improved, and his perfusion computed tomography (8 days after surgery)
      showed no excessive increased blood flow. CONCLUSIONS: We present a case of
      cerebral hyperperfusion syndrome and its successful treatment, distinct from that
      of cerebral vasospasm, after ruptured aneurysm clipping. In addition, we discuss
      the mechanism of this rare syndrome based on previous reports.

PMID- 29373233
TI  - Instantaneous VO2 from a wearable device.
AB  - We present a method for calculating instantaneous oxygen uptake (VO2) through the
      use of a non-invasive and non-obtrusive (i.e. without a face mask) wearable
      device, together with its clinical evaluation against a standard technique based
      upon expired gas calorimetry. This method can be integrated with existing
      wearable devices, we implemented it in the "Device for Reliable Energy
      Expenditure Monitoring" (DREEM). The DREEM comprises a single lead
      electrocardiogram (ECG) device combined with a tri-axial accelerometer and is
      worn around the waist. Our clinical evaluation tests the developed method against
      a gold standard for VO2, expired gas calorimetry, using an ethically approved
      protocol comprising active exercise and sedentary periods. The study was
      performed on 42 participants from a wide sample population including healthy
      people, athletes and an at-risk health group including persons affected by
      obesity. We developed an algorithm combining heart rate (HR) and the integral of
      absolute acceleration (IAA), with results showing a correlation of r = 0.93 for
      instantaneous VO2, and r = 0.97 for 3 min mean VO2, this is a considerably
      improved estimation of VO2 in comparison to methods utilising HR and IAA
      independently.

PMID- 29373234
TI  - Design, optimisation and testing of a compact, inexpensive elastic element for
      series elastic actuators.
AB  - This paper presents the development of a compact torsion spring for use as an
      elastic element in a lightweight series elastic actuator for an active orthosis.
      This orthosis is going to be utilised as an assistive device for motorically
      impaired stroke-patients. In the design a two-step optimisation strategy was
      implemented to meet all requirements for the torsion spring. The first step was
      to identify a promising topology for the element. In the second step, the shape
      was optimised based on a finite element model using two different optimisation
      methods in order to minimise the von Mises equivalent stresses. Four promising
      variants of the identified topology were extracted from these calculations, one
      of which was then chosen as the final design. A prototype was manufactured by a
      laser cutting process, which is a new procedure in the context of elastic
      elements for series elastic actuators. The calculation results were validated
      successfully by measurement of the spring properties of this prototype.

PMID- 29373235
TI  - Oral prednisolone in preschool children with virus-associated wheeze: a
      prospective, randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Children of preschool age often have episodes of virus-associated
      wheeze, and research assessing efficacy of corticosteroids for paediatric wheeze
      exacerbations is inconclusive. METHODS: This non-inferiority, randomised, double
      blind, placebo-controlled trial was to compare the efficacy of placebo versus
      oral prednisolone in children aged 24-72 months presenting with virus-associated
      wheeze at the paediatric emergency department of Princess Margaret Hospital in
      Perth, WA, Australia. Eligible participants were randomly assigned (1:1) using a
      computer-generated random number program to receive placebo or prednisolone (1
      mg/kg per day) for 3 days. The primary outcome was total length of stay in
      hospital until ready for discharge. Following an analysis to test the hypothesis
      that placebo is non-inferior to prednisolone, a post-hoc superiority analysis was
      done to test the hypothesis that prednisolone was superior to placebo. A non
      inferiority margin of 10% was used to establish non-inferiority. Efficacy
      analyses were on a modified intention-to-treat basis, whereby patients were
      excluded from the final efficacy analysis if consent was withdrawn, two doses of
      study drug were vomited, or paperwork was lost. All participants were included in
      safety analyses. This study is registered with the Australian and New Zealand
      Clinical Trials Registry, number ACTRN12612000394842. FINDINGS: Between June 11,
      2012, and June 10, 2015, we screened 3727 patients for eligibility. 624 eligible
      patients were randomly assigned to treatment, and 605 patients were included in
      the modified intention-to-treat analysis (300 patients from the placebo group,
      305 patients from the prednisolone group). The median length of stay until ready
      for discharge was longer in the placebo group (540 min [IQR 124-971]) than in the
      prednisolone group (370 min [121-709]); placebo was inferior to prednisolone. In
      the post-hoc superiority analysis of 605 patients, the unadjusted ratio of
      geometric mean for length of stay was 0.79 (95% CI 0.64-0.97; p=0.0227) for the
      prednisolone group relative to the placebo group. No serious adverse events were
      reported during the study or follow-up period. One child in the placebo group had
      a non-specific maculopapular rash, which resolved spontaneously. Two children
      (one from each group) were reported to be hyperactive during follow-up
      assessments. INTERPRETATION: Oral prednisolone had a clear benefit over placebo
      at reducing the length of stay in children presenting to a paediatric emergency
      department with virus-associated wheeze and was well tolerated. FUNDING: Western
      Australian Department of Health.

PMID- 29373236
TI  - Hyperechogenicity of lenticulostriate vessels: A poor prognosis or a normal
      variant? A seven year retrospective study.
AB  - BACKGROUND: Lenticulostriate vasculopathy (LSV) is a hyperechogenicity of the
      lenticulostriate branches of the basal ganglia and/or thalamus' middle cerebral
      arteries and is frequently seen in neonatology. Our study primarily describes the
      perinatal data and long-term follow-up of newborns with lenticulostriate vessel
      hyperechoic degeneration. Secondly, it describes the cerebral imaging data as a
      function of perinatal factors and neurodevelopmental follow-up of these newborns.
      METHODS: This retrospective study assesses the outcome of newborns with LSV
      hyperechogenicity on cerebral ultrasound (two grades). These children were born
      between January 2008 and September 2015 and were treated in a large level III
      neonatal intensive care unit. Thirty-four term-equivalent age children underwent
      MRIs using a standardized protocol of T2, T1 3D, diffusion and spectro-MRI
      sequences. The MRIs retrospectively measured the white matter and basal ganglia
      apparent diffusion coefficients (ADC). RESULTS: Fifty-eight neonates, ranging
      from 25 to 42 weeks gestational age (GA), were diagnosed with LSV. There was a
      significantly increased high-grade LSV when accompanied by fetal heart rate
      abnormalities (p = 0.03) and the neonate's need for respiratory support at birth
      (P = 0.002). The mean ADC score was substantially superior in the high-grade
      versus the low-grade LSVs (p = 0.023). There were no noteworthy outcome
      differences between a high and low grade LSV. The mean ADC for basal ganglions
      was appreciably higher in children with a severe prognoses (death or
      developmental disorder) as compared to children with no abnormalities (p < 0.01).
      CONCLUSION: From the results of our study, it appears that a low-grade LSV could
      be considered as a normal variant. There are no unifying diagnostic criteria for
      LSV on cerebral ultrasound. With a cerebral MRI, the use of ADC values of basal
      ganglia may well underscore the importance of such data in predicting long-term
      outcomes.

PMID- 29373237
TI  - Bacilli-containing granuloma with subsequent granuloma annulare-like eruptions
      following Bacillus Calmette-Guerin vaccination.

PMID- 29373238
TI  - Effect of longitudinal changes of body fat on the incidence and regression of
      nonalcoholic fatty liver disease.
AB  - AIMS: To investigate the longitudinal association between changes in body fat
      amount and the incidence and regression of nonalcoholic fatty liver disease
      (NAFLD). METHODS: We performed a cohort study of 2017 subjects without liver
      disease or significant alcohol consumption from 2007 to 2008 and participated in
      a voluntary follow-up between 2011 and 2013. Of the 2017 subjects, we enrolled
      956 (47.4%) subjects who had available abdominal fat data in both 2007-2008 and
      2011-2013. NAFLD was diagnosed on the basis of ultrasonographic findings. Adipose
      tissue area was evaluated by computed tomography. RESULTS: We observed 145
      incident cases of NAFLD (22.6% of 642), and 79 subjects experienced a regression
      of NAFLD (25.2% of 314) during a median of 4.64 years. An increasing change in
      visceral adipose tissue (VAT) area was associated with a higher incidence of
      NAFLD (highest tertile vs. lowest tertile of VAT hazard ratio [HR] 2.45, 95%
      confidence interval [CI] 1.56-3.85, P for trend <0.001) in the multivariable
      analysis. An increasing change in VAT area was inversely associated with the
      regression of NAFLD (highest tertile vs. lowest tertile of VAT HR 0.40, 95% CI
      0.20-0.80, P for trend = 0.008). CONCLUSIONS: An increasing change in VAT area
      was longitudinally associated with a higher risk of incident NAFLD and inversely
      associated with the regression of NAFLD.

PMID- 29373239
TI  - Sorafenib and fluvastatin synergistically alleviate hepatic fibrosis via
      inhibiting the TGFbeta1/Smad3 pathway.
AB  - BACKGROUND: Effective strategies for the treatment of hepatic fibrosis are
      urgently in need. AIMS: To investigate the effect of the co-treatment of
      sorafenib and fluvastatin on hepatic fibrosis and the underlying mechanisms.
      METHODS: A diethylnitrosamine-induced hepatic fibrosis rat model was used to
      evaluate the anti-fibrosis effect. Epithelial mesenchymal transition (EMT) of
      hepatocytes and hepatic stellate cells (HSCs) in response to sorafenib and
      fluvastatin was explored. A co-treatment effect on TGFbeta1 expression was
      explored in the Kupffer cells of rats. The effect of co-treatment on the
      regulation of the TGFbeta1/Smad3 pathway was investigated in both L02 cells and
      LX-2 cells. RESULTS: Sorafenib and fluvastatin synergistically reduced collagen
      content, alpha-SMA expression, lamin level, and hyaluronic acid level in the rat
      hepatic model. Combination treatment significantly inhibited the expression of
      mesenchymal markers and promoted the expression of epithelial markers in
      hepatocytes. Co-treatment statistically suppressed the production of TGFbeta1 in
      Kupffer cells. Suppression of EMT in parallel with alleviated up-regulation of
      fibronectin and alpha-SMA expression was observed in TGFbeta1-activated LX-2
      cells. Mechanistically, sorafenib plus fluvastatin blocked the TGFbeta1/Smad3
      signaling pathway via inhibiting phosphorylation of TbetaR II in hepatocytes and
      HSCs. CONCLUSIONS: Sorafenib and fluvastatin synergistically alleviated
      diethylnitrosamine-induced hepatic fibrosis in rats. Sorafenib plus fluvastatin
      may be a potential combination treatment for hepatic fibrotic diseases.

PMID- 29373240
TI  - Sticking particles to solid surfaces using Moringa oleifera proteins as a glue.
AB  - Experimental studies have been made to test the idea that seed proteins from
      Moringa oleifera which are novel, natural flocculating agents for many particles
      could be used to promote adhesion at planar interfaces and hence provide routes
      to useful nanostructures. The proteins bind irreversibly to silica interfaces.
      Surfaces that had been exposed to protein solutions and rinsed were then exposed
      to dispersions of sulfonated polystyrene latex. Atomic force microscopy was used
      to count particle density and identified that the sticking probability was close
      to 1. Measurements with a quartz crystal microbalance confirmed the adhesion and
      indicated that repeated exposures to solutions of Moringa seed protein and
      particles increased the coverage. Neutron reflectivity and scattering experiments
      indicate that particles bind as a monolayer. The various results show that the 2S
      albumin seed protein can be used to fix particles at interfaces and suggest
      routes for future developments in making active filters or improved interfaces
      for photonic devices.

PMID- 29373241
TI  - French translation and cross-cultural adaptation of the Michigan Hand Outcomes
      Questionnaire and the Brief Michigan Hand Outcomes Questionnaire.
AB  - Patient-Reported Outcome Measures (PROMs) are important clinical devices for
      evaluating injuries and surgeries of the hand. However, some of the most widely
      used questionnaires, such as the MHQ and bMHQ, are currently unavailable in
      French, which prevents them from being used in the French Canadian province of
      Quebec as well as in other French-speaking nations. We therefore intend to
      develop valid and culturally adapted French translations of the afore-mentioned
      questionnaires. Two independent bilingual translators converted all English
      questionnaires to French. Two distinct translators then translated the French
      versions back to English in reverse-blinded fashion. Discrepancies between the
      original and second English versions were examined by a committee of four
      bilingual healthcare professionals before final French translations of all
      documents were produced. Thirty patients bilingual in French and English were
      then asked to complete the original and French versions of the MHQ and bMHQ.
      Their answers were compared in order to assess the accuracy of our translation.
      In light of these findings, revised French versions were produced. French
      versions of the MHQ and bMHQ questionnaires produced metrological qualities of
      validity and fidelity with an inter-class correlation superior to 0.90 and a
      kappa coefficient of 0.81 to 1. Clinical applicability revealed the distribution
      of scores according to disease process was reproducible between the English and
      French versions. PROM translation requires a rigorous process in order to achieve
      strong metrological qualities in both the original and translated versions. We
      produced French translations of the MHQ and bMHQ by abiding to the Beaton method
      of cross-cultural adaptation of self-reported measures.

PMID- 29373242
TI  - Fluticasone in mild to moderate atopic dermatitis relapse: A randomized
      controlled trial.
AB  - BACKGROUND: The long-term efficacy of corticosteroids to prevent atopic
      dermatitis (AD) relapses has partially been addressed in children. This study
      compared an intermittent dosing regimen of fluticasone propionate (FP) cream
      0.05% with its vehicle base in reducing the risk of relapse in children with
      stabilized AD. METHODS: A randomized controlled, multicentric, double-blind trial
      was conducted. Children (2-10 years) with mild/moderate AD (exclusion criteria:
      >30% affected body surface area and/or head) were enrolled into an Open-label
      Stabilization Phase (OSP) of up to 2 weeks on twice daily FP. Those who achieved
      treatment success entered the Double-blind Maintenance Phase (DMP). They were
      randomly allocated to receive FP or vehicle twice-weekly on consecutive days for
      16 weeks. The primary study endpoint was relapse rate; time to relapse and
      severity of disease were also studied. Kaplan-Meier estimates were calculated.
      RESULTS: Fifty-four patients (29 girls) entered the OSP (23 mild AD) and 49 (26
      girls) continued into the DMP. Mean age was 5.5 (SD: 2.8) and 5.1 (SD: 2.3) yrs
      for FP and vehicle groups, respectively. Four patients withdrew from the DMP (two
      in every group). Patients treated with FP twice weekly had a 2.7 fold lower risk
      of experiencing a relapse than patients treated with vehicle (relative risk 2.72,
      SD: 1.28; p=0.034). FP was also superior to vehicle for delaying time to relapse.
      Both treatment therapies were well tolerated. CONCLUSION: This long-term study
      shows that twice weekly FP provides an effective maintenance treatment to control
      the risk of relapse in children with AD.

PMID- 29373243
TI  - Haploidentical stem cell transplantation in a boy with chronic granulomatous
      disease.
AB  - Chronic granulomatous disease is a primary immunodeficiency caused by mutations
      in any one of the five components of the NADPH oxidase in phagocytic leucocytes.
      This causes impaired microbial killing, which leads to severe life-threatening
      bacterial and fungal infections. Currently, allogenic hematopoietic stem cell
      transplantation (HSCT) is the only curative treatment for chronic granulomatous
      disease, although gene therapy may provide a new therapeutic option for the
      treatment of patients with CGD. Haploidentical HSCT provides a potentially
      curative treatment option for patients who lack a suitably HLA-matched donor, but
      only a few cases have been reported in the literature. Herein, we report a boy
      with X-linked chronic granulomatous disease treated successfully by
      haploidentical HSCT with post-transplant cyclophosphamide using a treosulfan
      based conditioning regimen.

PMID- 29373244
TI  - Race and Sex Disparities in Outcomes of Dialysis Access Maintenance
      Interventions.
AB  - PURPOSE: To determine whether utilization and outcomes of dialysis access
      maintenance interventions vary by patient race or sex. MATERIALS AND METHODS:
      Data for this retrospective cohort study of first-time arteriovenous (AV) access
      recipients were drawn from a 5% sample of Medicare beneficiaries, containing
      claims from all clinical settings (2009-2014) in 2,693 patients who received
      their first AV fistula/graft in 2009. Maintenance interventions-angiography,
      angioplasty, thrombolysis, stent placement, and venous embolization-were
      identified by corresponding Current Procedural Terminology codes. Outcomes of
      primary patency (PP), postinterventional primary patency (PIPP), and
      postinterventional secondary patency (PISP) were calculated with utilization
      records. Associations between demographic data and patency times were evaluated
      by a multivariate survival approach, controlling for baseline differences in
      patient age, comorbid disease, type of dialysis access, and interventionist
      specialty. RESULTS: AV grafts (AVGs) were created with greater frequency in women
      (32% vs 23% in men; P < .001) and minority patients (39% in black, 32% in
      Hispanic, and 29% in Asian patients vs 21% in white patients; P < .001). Women
      were at greater hazards for loss of PP (hazard ratio [HR], 1.49; 95% confidence
      interval [CI], 1.09-2.14) and PIPP (HR, 1.42; 95% CI, 1.01-2.00). Black patients
      were at greater hazards for loss of PP (HR, 1.37; 95% CI, 1.23-1.54) and PISP
      (HR, 1.29; 95% CI, 1.01-1.65). AVG creation predisposed patients to patency loss
      in all models (P < .001). CONCLUSIONS: Dialysis access patency rates are lower
      for women and black patients. More frequent primary AVG creation in women and
      minority patients additionally predisposes these patients to patency loss.

PMID- 29373245
TI  - Structured Reporting of IR Procedures: Effect on Report Compliance, Accuracy, and
      Satisfaction.
AB  - PURPOSE: To compare effect of free-text versus structured reporting of IR
      procedures on report quality and report coding and value. MATERIALS AND METHODS:
      In this retrospective study, 432 common consecutive free-text IR reports created
      during 4 months (from September 2013 to December 2013) before implementation of
      structured reporting (February 2014) and 415 structured IR reports created after
      implementation (from September 2014 to December 2014) were reviewed to assess
      ease of use and compliance with reporting requirements for regulatory
      requirements and coding. IR staff and trainees and referring physicians to IR
      were surveyed on procedure report attributes, such as detail, quality, and
      clarity. RESULTS: Structured reporting increased compliance with reporting
      fluoroscopy time, radiation dose, and contrast administration compared with free
      text reports (402/432 [93.1%] vs 251/415 [60.5%], P < .001; 402/432 [93.1%] vs
      242/415 [58.3%], P < .001; and 395/432 [91.4%] vs 257/415 [61.9%], P < .001).
      Structured reporting decreased addendum requests for insufficient documentation
      from 43% (121/435 [28%] to 50/415 [12%], P = .01). Most IR physicians found
      structured reports to require less time to complete (21/26 [81%]), to be easier
      to complete (23/26 [89%]), and to have a similar or higher level of detail (19/26
      [73%]) compared with free-text reports. Referring physicians were more satisfied
      with structured reports compared with free-text reports (6.9/10 vs 5.6/10, P =
      .03). CONCLUSIONS: Structured IR reporting compared with free-text reporting
      improves compliance with radiation dose and contrast reporting, reporting and
      coding efficiency, and satisfaction among IR and referring physicians.

PMID- 29373246
TI  - Yttrium-90 Radioembolization of the Right Inferior Phrenic Artery in 20 Patients
      with Hepatocellular Carcinoma.
AB  - PURPOSE: To address the feasibility of infusion of yttrium-90 (90Y) glass
      microspheres directly through the right inferior phrenic artery (RIPA). MATERIALS
      AND METHODS: From November 2015 to May 2017, 20 patients underwent 90Y
      radioembolization through the RIPA. When the systemic-to-pulmonary shunt was
      demonstrated on C-arm computed tomography (CT) of the RIPA, prophylactic
      embolization by polyvinyl alcohol (PVA) particles was performed prior to infusion
      of 90Y glass microspheres. Follow-up CT scans were retrospectively reviewed for
      pulmonary complications. Tumor response was determined by the modified Response
      Evaluation Criteria in Solid Tumors. RESULTS: Nine (45%) patients had systemic-to
      pulmonary shunts on C-arm CT images of the RIPA. The feeder of the systemic-to
      pulmonary shunt was the azygoesophageal branch (n = 7) and the anterior branch (n
      = 2). The mean activity of 90Y glass microspheres infused into the RIPA was 0.49
      GBq (range, 0.19-1.55 GBq). No patient had symptomatic radiation pneumonitis or
      cutaneous complications during follow-up. Seven patients had focal atelectasis (n
      = 5), focal ground-glass opacity (n = 2), and/or a small amount of pleural
      effusion (n = 2) on follow-up image. Best tumor response fed by the RIPA was
      complete response (n = 4), partial response (n = 9), stable disease (n = 2),
      progressive disease (n = 4), and unevaluable (n = 1). CONCLUSION: The
      administration of 90Y glass microspheres through the RIPA may be safe after
      embolization of a systemic-to-pulmonary shunt identified on C-arm CT.

PMID- 29373247
TI  - Discrimination and identification of Q-markers based on 'Spider-web' mode for
      quality control of traditional Chinese medicine.
AB  - BACKGROUND: The safety and effectiveness of traditional Chinese medicine (TCM) in
      clinical practice is directly related to the quality of TCM. And, the quality
      control of TCM is a pivotal issue to the quality of TCM, but also an obstacle
      impeding the modernization of TCM. PURPOSE: The purpose of this work is to
      compile and develop a strategy based on discrimination and identification of
      quality markers (Q-markers) for quality control of TCM. METHODS: Mainly
      established by seven variables derived from four dimensions including content,
      stability, pharmacokinetics and pharmacology, the 'Spider-web' mode was
      undertaken to assess the Q-marker property of candidate compounds originated from
      TCM by taking regression area (A) and coefficient variation (CV) of the tested
      compounds into account. The importance index (ImI), ImI = A * 1/CV, was suggested
      to focus Q-markers. RESULTS: The compounds with larger regression area (A) and
      less coefficient variation (CV) are preferentially adopted as Q-markers, which
      should possess the satisfactory properties of content, stability,
      pharmacokinetics and pharmacological activity. To the contrary, the compounds are
      excluded on the grounds of the unsatisfactory Q-markers' property, less
      regression area (A) and larger coefficient variation (CV), which cannot represent
      the quality of TCM. CONCLUSIONS: The 'Spider-web' mode can filter out the
      redundant constituents and focus on the key indexes of quality control - Q
      markers. The screened Q-markers possess the optimal integrated properties of
      content, stability, pharmacokinetics and pharmacology among the numerous and
      complicated ingredients of TCM, which can comprehensively characterize inherent
      quality of TCM. In summary, the novel strategy established in this work provides
      a valuable perspective for the quality control of TCM.

PMID- 29373249
TI  - Percutaneous Repair of a Giant Aortic Aneurysm.

PMID- 29373248
TI  - Measurement of coronary bifurcation angle with coronary CT angiography: A phantom
      study.
AB  - PURPOSE: Accurate determination of the bifurcation angle and correlation with
      plaque buildup may lead to the prediction of coronary artery disease (CAD). This
      work evaluates two techniques to measure bifurcation angles in 3D space using
      coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: Nine
      phantoms were fabricated with different bifurcation angles ranging from 55.3
      degrees  to 134.5 degrees . General X-ray and CCTA were employed to acquire 2D
      and 3D images of the bifurcation phantoms, respectively. Multiplanar reformation
      (MPR) and volume rendering technique (VRT) were used to measure the bifurcation
      angle between the left anterior descending (LAD) and left circumflex arteries
      (LCx). The measured angles were compared with the true values to determine the
      accuracy of each measurement technique. Inter-observer variability was evaluated.
      The two techniques were further applied on 50 clinical CCTA cases to verify its
      clinical value. RESULTS: In the phantom setting, the mean absolute differences
      calculated between the true and measured angles by MPR and VRT were 2.4 degrees
      +/-2.2 degrees  and 3.8 degrees +/-2.9 degrees , respectively. Strong correlation
      was found between the true and measured bifurcation angles. Furthermore, no
      significant differences were found between the bifurcation angles measured using
      either technique. In clinical settings, large difference of 12.0 degrees +/-10.6
      degrees  was found between the two techniques. CONCLUSION: In the phantom
      setting, both techniques demonstrated a significant correlation to the true
      bifurcation angle. Despite the lack of agreement of the two techniques in the
      clinical context, our findings in phantoms suggest that MPR should be preferred
      to VRT for the measurement of coronary bifurcation angle by CCTA.

PMID- 29373250
TI  - Selection of the Best of 2017 in Vascular Risk and Cardiac Rehabilitation.

PMID- 29373251
TI  - Ultrasound-assessed Pulmonary Contusion After CPR.

PMID- 29373252
TI  - Selection of the Best of 2017 in Acute and Chronic Heart Failure.

PMID- 29373253
TI  - Effect of Early Treatment With Ivabradine Plus Beta-blockers on Long-term
      Outcomes in Patients Hospitalized With Systolic Heart Failure.

PMID- 29373254
TI  - Early Sacubitril/Valsartan-driven Benefit on Exercise Capacity in Heart Failure
      With Reduced Ejection Fraction: A Pilot Study.

PMID- 29373255
TI  - Delirium in Patients With Heart Failure: Influence of Attendance Times in an
      Emergency Department.

PMID- 29373256
TI  - Severe obstructive sleep apnea in children with elevated blood pressure.
AB  - The objective was to determine the prevalence of habitual snoring and obstructive
      sleep apnea (OSA) in a cohort of children referred for elevated blood pressure
      (BP), and to determine the association between OSA and BP elevation, learning
      difficulties, and behavioral problems. We performed a retrospective review of 446
      consecutive new patients referred for elevated BP. One hundred four (23%) had
      habitual snoring. Patients with habitual snoring were more likely to be obese
      (86.5 vs. 55.6%, P < .001) and to have Medicaid insurance (52.4 vs. 36%, P =
      .004). Seventy-four patients had polysomnography, of which 57 (77%) had OSA; 21
      (37%) had severe OSA. Severe OSA was associated with higher office systolic BP
      index after adjusting for body mass index, age, sex, and socioeconomic status
      (beta = 0.07, P = .014). Fifty-two percent of patients with severe OSA had office
      systolic BP in the Stage 2 hypertension range. Children with habitual snoring or
      OSA were not at increased risk of receiving school services for a learning
      disability or receiving medications for inattention or mood problems. In summary,
      habitual snoring is common in children referred for elevated BP, and those with
      severe OSA are at higher risk of significantly increased BP.

PMID- 29373257
TI  - Immunomodulatory Nonstructural Proteins of Influenza A Viruses.
AB  - Influenza epidemics and pandemics still represent a severe public health threat
      and cause significant morbidity and mortality worldwide. As intracellular
      parasites, influenza viruses are strongly dependent on the host cell machinery.
      To ensure efficient production of progeny viruses, viral proteins extensively
      interfere with cellular signalling pathways to inhibit antiviral responses or to
      activate virus-supportive functions. Here, we review various functions of the
      influenza virus nonstructural proteins NS1, PB1-F2, and PA-X in infected cells
      and how post-transcriptional modifications of these proteins affect the viral
      life cycle. Furthermore, we discuss newly discovered interactions between these
      proteins and the antiviral interferon response.

PMID- 29373258
TI  - Fast growing melanoma following treatment with vismodegib for locally advanced
      basal cell carcinomas: report of two cases.

PMID- 29373259
TI  - An unusual swelling of the supraorbital region.

PMID- 29373260
TI  - Thalamic Directional Deep Brain Stimulation for tremor: Spend less, get more.
AB  - BACKGROUND: Directional Deep Brain Stimulation (D-DBS) allows axially asymmetric
      electrical field shaping, away from structures causing side-effects. However,
      concerns regarding the impact on device lifespan and complexity of the monopolar
      survey have contributed to sparing use of these features. OBJECTIVE: To
      investigate whether chronically implanted D-DBS systems can improve the
      therapeutic window, without a negative impact on device lifespan, in thalamic
      deep brain stimulation (DBS). METHODS: We evaluated stable outcomes of initial
      programming sessions (4-6 weeks post-implantation) retrospectively in 8 patients
      with drug-resistant disabling tremor syndromes. We assessed the impact of
      directional stimulation on the Therapeutic Window (TW), Therapeutic Current
      Strength (TCS), tremor scores, disability scores and total electrical energy
      delivered. Finally, we performed Volume of Tissue Activation (VTA) modelling,
      based on a range of parameters. RESULTS: We report significant gains in TW (91%)
      and reductions in TCS (31%) with stimulation in the best direction compared to
      best omnidirectional stimulation alternative. Tremor and ADL scores improvements
      remained unchanged at six months. There was no increase in averaged IPG power
      consumption (there is a 6% reduction over the omnidirectional-only alternative).
      Illustrative VTA modelling shows that D-DBS achieves 85% of the total activation
      volume at just 69% of the stimulation amplitude of non-directional configuration.
      CONCLUSIONS: D-DBS can improve the therapeutic window over non-directional DBS,
      leading to significant reduction in disability that may be sustained without
      additional reprogramming visits. When averaged across the cohort, power output
      and predicted device lifespan was not impacted by the use of directional
      stimulation in this study.

PMID- 29373261
TI  - Facilitators and barriers to pregnant women's participation in research: A
      systematic review.
AB  - BACKGROUND: Although there is consensus among many that exclusion of pregnant
      women from clinical research should be justified, there is uncertainty as to
      whether and why pregnant women themselves would be willing to participate even if
      they were found to be eligible. The objective was to identify the reasons why
      pregnant women participate in clinical research and thereby to distinguish
      between facilitators and barriers. METHODS: We conducted a systematic review of
      articles regarding pregnant women's reasons for participation in clinical
      research. We used the PubMed/MEDLINE, EMBASE, PsycINFO and CINAHL databases and
      retrieved additional articles through manually searching the reference lists. We
      included all articles that reported on pregnant women's reasons for participation
      in clinical research. We accumulated all reasons that were mentioned in the total
      of articles and collated them to themes, classifying these themes as a
      facilitator or a barrier. RESULTS: The search identified thirty articles that met
      the inclusion criteria. Themes classified as facilitators: aspirational benefits,
      collateral benefits, direct benefits, third party influence and lack of
      inconvenience. Themes classified as barriers: inconveniences, risks,
      randomisation, lack of trust in research enterprise, medical reasons and third
      party influence. CONCLUSIONS: Pregnant women report mostly altruistic and
      personal reasons for their willingness to participate in clinical research, while
      barriers primarily relate to inconveniences. It appears that pregnant women's
      described reasoning is similar to the described reasoning of non-pregnant
      research subjects. Enhancing the facilitators and overcoming the barriers is the
      next step to increase the evidence-base underlying maternal and foetal health.

PMID- 29373262
TI  - A longitudinal study of perinatal depression among Chinese high-risk pregnant
      women.
AB  - BACKGROUND: Information is needed on the prevalence of depression in Chinese
      women with medically defined complications across the perinatal period, as well
      as key risk factors to develop appropriate perinatal mental health services and
      ensure the services target those most in need. AIM: The goal of this study was to
      examine whether women's perinatal depression scores change across the perinatal
      period and evaluate risk factors associated with postnatal depression at 6-weeks
      after delivery. METHODS: A sample of 167 Chinese pregnant women with medically
      defined complications and an Edinburgh Postnatal Depression Scale>=9 and/or a
      Postpartum Depression Screening Scale>=60 were followed throughout early
      pregnancy (<28 weeks), late pregnancy (>28 weeks), 3-days and 6-weeks after
      delivery. FINDINGS: Repeated measures analysis of variance showed that there were
      significant differences on the Edinburgh Postnatal Depression Scale and
      Postpartum Depression Screening Scale scores at each time point between high-risk
      depressed and low-risk depressed groups. Binary logistic regression indicated a
      significant association between postnatal depression at 6-weeks after delivery
      and depression in late pregnancy and 3-days after delivery, postnatal stress
      events, postnatal complications, and concerns about the fetus. CONCLUSIONS:
      Postnatal depression is a common condition with limited research among Chinese
      pregnant women with medically defined complications. Additional research is
      warranted to develop strategies to identify high-risk depressed pregnant women as
      well as effective treatment options during the perinatal period.

PMID- 29373263
TI  - Legionella pneumonia appeared during hospitalization in a patient with
      hematological malignancy confirmed by sputum culture after negative urine antigen
      test.
AB  - Legionella pneumophila is recognized as a common causative organism for community
      acquired pneumonia, but it is rarely a causative organism for hospital-acquired
      pneumonia, except in cases of hospital outbreak. Recently, most of the Legionella
      cases have been diagnosed using the urine antigen test. However, this test can
      reliably detect only L. pneumophila serogroup 1. Here we report a 63-year-old
      male patient who was recently diagnosed with acute leukemia and treated with
      chemotherapy and who developed pneumonia on hospital day 8 during the nadir
      phase. He was later diagnosed with Legionella pneumonia by culture despite a
      negative urine antigen test. This case suggests that Legionella pneumonia is an
      important differential diagnosis for pneumonia in inpatients in the early phase
      of hospitalization and that when Legionella infection is clinically suspected,
      culture using selective media or molecular tests should be performed even if the
      urine antigen test is negative.

PMID- 29373265
TI  - Susceptibility of Clostridium species isolated in Japan to fidaxomicin and its
      major metabolite OP-1118.
AB  - The narrow-spectrum macrocyclic antibiotic fidaxomicin is approved for treatment
      of Clostridium difficile infection in many countries and is currently under
      evaluation in Japan for this indication. This study was conducted to evaluate the
      effects of fidaxomicin and its major metabolite, OP-1118, on Clostridium spp.
      isolated in Nagasaki University Hospital, Japan. Isolates were cultured and
      antimicrobial susceptibility analyses performed according to the Clinical
      Laboratory Standards Institute methods. Ninety-eight isolates were obtained
      between 2012 and 2015, 50 of C. difficile and 48 of eight other Clostridium spp.
      Fidaxomicin had the lowest minimum inhibitory concentration (MIC) of the
      antimicrobials tested against C. difficile, with MIC90 (MIC range) 0.12 MUg/mL
      (0.015-0.25), versus vancomycin MIC90 0.5 MUg/mL (0.5), metronidazole MIC90 0.5
      MUg/mL (0.12-0.5), and OP-1118 MIC90 4.0 MUg/mL (0.5-4.0). Fidaxomicin and OP
      1118 each had a similar spectrum of activity against the other Clostridium spp.
      C. butyricum and the 29 fidaxomicin- and OP-1118-susceptible C. perfringens
      isolates had the lowest MIC values, and C. bolteae and C. hathewayi higher. All
      the C. ramosum isolates (n = 6) and one of 30 C. perfringens isolates had low
      susceptibility to fidaxomicin and OP-1118 (i.e., MIC >64 MUg/mL). In summary,
      this study showed that fidaxomicin was active against a number of Clostridium
      spp., including C. difficile. Fidaxomicin was generally more effective than its
      major metabolite OP-1118, but both showed a similar spectrum of activity,
      suggesting that OP-1118 contributes to the antimicrobial activity of fidaxomicin.
      These findings were broadly in accordance with those of similar studies conducted
      in other settings.

PMID- 29373266
TI  - Molecular diagnosis and characterization of a culture-negative mycotic aneurysm
      due to ST54 Haemophilus influenzae type b with PBP 3 alterations.
AB  - Mycotic aneurysm is a rare but life-threatening disease that warrants an
      integrated therapeutic approach involving surgical intervention and prolonged
      antibiotic use. However, the causative organisms are often unidentified because
      antibiotics started empirically render blood and tissue cultures negative.
      Molecular diagnosis has been reported to be useful in such culture-negative
      cases. We report a case of a culture-negative mycotic aortic aneurysm due to
      Haemophilus influenzae, diagnosed by direct 16S rRNA polymerase chain reaction
      (PCR) and sequencing of the resected aneurysm tissue. PCR for serotype revealed
      type b, and PCR and sequencing of the ftsI gene revealed alterations in
      penicillin-binding protein 3, suggesting resistance to ampicillin. Multilocus
      sequence typing demonstrated that the isolate belonged to sequence type 54.

PMID- 29373264
TI  - Disseminated fusariosis emerged from prolonged local genital infection after cord
      blood transplantation.
AB  - Disseminated fusariosis (DF) is a rare life threatening fungal infection in
      immunocompromised hosts. We herein report a case of a fatal DF mimicking
      varicella zoster virus (VZV) infection that was emerged from a localized genital
      infection during cord blood transplantation (CBT) in a patient with severe
      aplastic anemia (SAA). The patient developed an ulcer following small painful
      vesicles mimics herpes simplex virus infection (HSV) on the glans penis before
      CBT, but a Fusarium species was identified. Despite administration of
      voriconazole, liposomal amphotericin B and granulocyte transfusion, the lesion
      was extended to extensive skin looked like VZV infection and the patients died
      after CBT. Massive fusarium infiltration was detected in multiple organs at
      autopsy. A genetic analysis of the mold identified Fusarium solani after his
      death. It should be noted that in patients with fusarium infection, localized and
      disseminated lesions of fusarium infection sometimes mimic HSV and VZV
      infections, which hampers an early diagnosis.

PMID- 29373267
TI  - Mediastinal, subcutaneous and multiple muscular abscesses caused by group B
      streptococcus serotype VIII in a type 2 diabetes mellitus patient.
AB  - We report a case of mediastinal subcutaneous and multiple muscular abscesses
      caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus
      patient. The patient arrived at the hospital with the chief complaint of
      immobility, and blood examination results suggested an acute infection and poorly
      controlled diabetes mellitus. Group B streptococcal bacteria were cultured from
      the patient's blood, and identified as serotype VIII upon further analysis. The
      patient recovered without any sequelae after percutaneous drainage, antibiotic
      therapy, and intensive glycemic control. Although the incidence of group B
      streptococcal infection in non-pregnant adults has recently increased in many
      developed countries, information on serotype VIII infection is quite limited. The
      reason is that serotype VIII group B streptococci are a Japan-specific serotype,
      and rarely cause invasive infections, even in Japan. Therefore, further
      surveillance and case reports should be documented in the future.

PMID- 29373268
TI  - Meningococcal meningitis with neurological complications and meningococcemia due
      to serogroup W sequence type 11 complex.
AB  - Invasive meningococcal disease (IMD) caused by the serogroup W (MenW) sequence
      type-11 complex strain has recently emerged worldwide. Meningococcal infections
      due to this strain are associated with high case fatality and often atypical
      clinical manifestations. However, the annual IMD incidence was low, and MenW is
      rare in Japan. We described the first Japanese case of meningococcal meningitis
      and meningococcemia caused by this strain in a previously healthy 27-year-old
      woman. This case showed various neurological complications such as abducens
      palsy, cerebellitis, and cerebellar infarction, and reactive arthritis. This case
      provides useful information on the possibility of spreading IMD strains and the
      cause of various complications.

PMID- 29373269
TI  - Surrogating and redirection of pyrazolo[1,5-a]pyrimidin-7(4H)-one core, a novel
      class of potent and selective DPP-4 inhibitors.
AB  - The initial focus on characterizing novel pyrazolo[1,5-a]pyrimidin-7(4H)-one
      derivatives as DPP-4 inhibitors, led to a potent and selective inhibitor compound
      b2. This ligand exhibits potent in vitro DPP-4 inhibitory activity (IC50: 80 nM),
      while maintaining other key cellular parameters such as high selectivity, low
      cytotoxicity and good cell viability. Subsequent optimization of b2 based on
      docking analysis and structure-based drug design knowledge resulted in d1.
      Compound d1 has nearly 2-fold increase of inhibitory activity (IC50: 49 nM) and
      over 1000-fold selectivity against DPP-8 and DPP-9. Further in vivo IPGTT assays
      showed that compound b2 effectively reduce glucose excursion by 34% at the dose
      of 10 mg/kg in diabetic mice. Herein we report the optimization and design of a
      potent and highly selective series of pyrazolo[1,5-a]pyrimidin-7(4H)-one DPP-4
      inhibitors.

PMID- 29373270
TI  - Reversed isoniazids: Design, synthesis and evaluation against Mycobacterium
      tuberculosis.
AB  - Novel reversed isoniazid (RINH) agents were synthesized by covalently linking
      isoniazid with various efflux pump inhibitor (EPI) cores and their structural
      motifs. These RINH agents were then evaluated for anti-mycobacterial activity
      against sensitive, isoniazid mono-resistant and MDR clinical isolates of M.
      tuberculosis and a selected number of compounds were also tested ex vivo for
      intracellular activity as well as in the ethidium bromide (EB) assay for efflux
      pump inhibition efficacy. The potency of some compounds against various strains
      of M. tuberculosis (4a-c, 7 and 8; H37Rv-MIC99 <=1.25 uM, R5401-MIC99 <=2.5 uM,
      X_61-MIC99 <=5 uM) demonstrated the potential of the reversed anti-TB agent
      strategy towards the development of novel anti-mycobacterial agents to address
      the rapidly growing issue of resistance. Further, macrophage activity with >90%
      inhibition by 1a-c and 3b (MIC90 <=13.42 uM) and inhibition of EB efflux
      demonstrated by these compounds are encouraging.

PMID- 29373271
TI  - Synthesis, biological evaluation and docking study of a new series of di
      substituted benzoxazole derivatives as selective COX-2 inhibitors and anti
      inflammatory agents.
AB  - A new series of substituted-N-(3,4-dimethoxyphenyl)-benzoxazole derivatives 13a
      13p was synthesized and evaluated in vitro for their COX (I and II) inhibitory
      activity, in vivo anti-inflammatory and ulcerogenic potential. Compounds 13d,
      13h, 13k, 13l and 13n exhibited significant COX-2 inhibitory activity and
      selectivity towards COX-2 over COX-1. These selected compounds were screened for
      their in vivo anti-inflammatory activity by carrageenan induced rat paw edema
      method. Among these compounds, 13d was the most promising analogs of the series
      with percent inhibition of 84.09 and IC50 value of 0.04 uM and 1.02 uM (COX-2 and
      COX-1) respectively. Furthermore, ulcerogenic study was performed and tested
      compounds (13d, 13h, 13k, 13l) demonstrated a significant gastric tolerance than
      ibuprofen. Molecular docking study was also performed with resolved crystal
      structure of COX-2 to understand the binding mechanisms of newly synthesized
      inhibitors in the active site of COX-2 enzyme and the results were found to be
      concordant with the biological evaluation studies of the compounds. These newly
      synthesized inhibitors also showed acceptable pharmacokinetic profile in the in
      silico ADME/T analyses.

PMID- 29373272
TI  - Chemosynthetic homologues of Mycoplasma pneumoniae beta-glycolipid antigens for
      the diagnosis of mycoplasma infectious diseases.
AB  - Mycoplasma pneumoniae expresses beta-glycolipids (beta-GGLs) in cytoplasmic
      membranes, which possess a unique beta(1 -> 6)-linked disaccharide epitope, which
      has high potential in biochemical and medicinal applications. In the present
      study, a series of beta-GGLs homologues with different acyl chains (C12, C14,
      C16, and C18) were prepared from a common precursor. An ELISA assay using an anti
      (beta-GGLs) monoclonal antibody indicated that the synthetic homologues with long
      acyl chains had greater diagnostic potential in the order C18 > C16 > C14 > C12.
      Toward a simultaneous detection of natural glycolipids by mass spectrometry (MS),
      a deuterium-labeled C16 homologue (beta-GGL-C16-d3) was prepared and applied as
      an internal standard for a high-resolution electrospray ionization MS (ESI-MS)
      analysis. The ESI-MS analysis was used to identify and quantify acyl homologues
      (C16/C16, C16/C18, and C18/C18) of beta-GGL-C16 in cultured M. pneumoniae. A beta
      GGLs homologue with a 1,2-diacetyl group (C2) was also prepared as a "water
      soluble" glycolipid homologue and characterized by 1H NMR spectroscopy. We
      envisage that each of these chemosynthetic homologues will provide promising
      approaches to solve medical and biological problems associated with mycoplasma
      infectious diseases (MIDs).

PMID- 29373273
TI  - Generation of a New Disease-specific Prognostic Score for Patients With Brain
      Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS
      Score) and Validation of Two Other Indices.
AB  - INTRODUCTION: Patients with small-cell lung cancer (SCLC) demonstrate an
      exception in the treatment of brain metastases (BM), because in patients with
      SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality.
      The purpose of this study was to develop a prognostic score for patients with
      brain metastases from SCLC treated with WBRT. PATIENTS AND METHODS: The present
      study was conducted utilizing a single-institution, previously described,
      retrospective database of patients with SCLC who were treated with WBRT (n =
      221). Univariate and multivariate analyses were performed to generate the "brain
      metastases from SCLC score" (BMS score) based on favorable prognostic factors:
      Karnofsky performance status (KPS > 70), extracerebral disease status (stable
      disease/controlled), and time of appearance of BM (synchronous). Furthermore, the
      disease-specific graded prognostic assessment score as well as the recursive
      partitioning analysis (RPA) were performed and compared with the new BMS score by
      using the log-rank (Mantel-Cox) test. RESULTS: BMS score and RPA showed the most
      significant differences between classes (P < .001). BMS score revealed a mean
      overall survival (OS) of 2.62 months in group I (0-1 points), 6.61 months in
      group II (2-3 points), and 12.31 months in group III (4 points). The BMS score
      also identified the group with the shortest survival (2.62 months in group I),
      and the numbers of patients in each group were most equally distributed with the
      BMS score. CONCLUSION: The new BMS score was more prognostic than the RPA and
      disease-specific graded prognostic assessment scores. The BMS score is easy to
      use and reflects known prognostic factors in contemporary patients with SCLC
      treated with WBRT. Future studies are necessary to validate these findings.

PMID- 29373274
TI  - Efficacy and Safety of Ramucirumab With Docetaxel Versus Placebo With Docetaxel
      as Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer: A Subgroup
      Analysis According to Patient Age in the REVEL Trial.
AB  - INTRODUCTION: Ramucirumab, a recombinant human immunoglobulin G1 monoclonal
      antibody receptor antagonist designed to block the ligand-binding site of
      vascular endothelial growth factor receptor-2 (VEGFR-2), was evaluated as second
      line treatment in combination with docetaxel in patients with non-small-cell lung
      cancer in the REVEL trial (NCT01168973). Ramucirumab significantly improved
      overall survival (OS) and progression-free survival (PFS). We report age subgroup
      analysis results primarily on the basis of a 65-year cutoff. PATIENTS AND
      METHODS: Patients were randomized 1:1 to ramucirumab with docetaxel or placebo
      with docetaxel (n = 1253). Of these, 798 were younger than 65 years (ramucirumab,
      n = 391; control, n = 407) and 455 were 65 years or older (ramucirumab, n = 237;
      control, n = 218). Treatment comprised 21-day cycles of 75 mg/m2 docetaxel with
      10 mg/kg ramucirumab or placebo. Prespecified age subgroup analyses were
      performed, including OS, PFS, and objective response rate. Quintiles age analysis
      was conducted to establish a relationship between efficacy and age. The Lung
      Cancer Symptom Scale (LCSS) measured quality of life outcomes. Safety was
      assessed according to adverse events (AEs). RESULTS: Patients younger than 65
      years showed favorable OS outcomes with ramucirumab treatment (hazard ratio [HR],
      0.74; 95% confidence interval [CI], 0.62-0.87; P < .001) and PFS (HR, 0.68; 95%
      CI, 0.59-0.79; P < .001). In patients 65 years or older, benefits of ramucirumab
      were not as evident; after model adjustment for prognostic factors, OS and PFS
      HRs were 0.96 (95% CI, 0.77-1.21; P = .04) and 0.87 (95% CI, 0.71-1.05; P = .03),
      respectively. Age analysis according to quintiles showed HRs favoring ramucirumab
      for all age groupings. LCSS scores and AEs did not considerably differ between
      age groups. CONCLUSION: In this subgroup analysis, true treatment effect
      differences on the basis of age have not been established, and treatment should
      not be deterred solely because of age.

PMID- 29373275
TI  - [Procrastination in the self-management of gestational diabetes].

PMID- 29373276
TI  - [Acute myelitis by blast effect].

PMID- 29373277
TI  - [Two successive opportunistic infections associated with severe CD4
      lymphocytopenia revealing systemic sarcoidosis].

PMID- 29373278
TI  - [Arterial hemodynamic parameters and cardiovascular risk in HIV patients with
      controlled infection].
AB  - Although viral replication is apparently controlled with highly active
      antiretroviral therapy, cardiovascular risk of patients living with HIV remains a
      concern in clinical practice with population ageing. Cardiovascular risk profile
      in patients living with HIV is changing with the emergence of new parameters
      related to the persistence of residual viral replication, the antecedent and
      severity of immunodepression, the resulting chronic inflammation, as well as
      prolonged exposure to antiretroviral drugs and "classical" cardiovascular risk
      factors. Estimating risk models in patients living with HIV are not sufficient to
      integrate duration of exposure and control quality of all cardiovascular risk
      factors at the individual level. Aortic stiffness is a marker of the alteration
      of structural and functional properties of the wall of the large arterial trunks.
      This marker has an independent predictive value for total and cardiovascular
      mortality in the general population but also in the presence of risk factors and
      may offer clinical information about accelerated vascular ageing in people living
      with HIV. Aortic stiffness can be estimated non-invasively by applanation
      tonometry with carotid-femoral pulse wave velocity. This measure may be useful in
      clinical practice for early identification of at risk patients. Study of the
      determinants of aortic stiffening process in this population may optimize
      cardiovascular prevention.

PMID- 29373279
TI  - Hepatic epithelioid hemangioendothelioma: A misdiagnosed rare liver tumor.

PMID- 29373280
TI  - [Light chain multiple myeloma revealed by a dorsal epidural compressive tumor].

PMID- 29373281
TI  - Giant transverse colon diverticulum.

PMID- 29373282
TI  - [Forensic medical examination of adolescent and adult victims of sexual assault
      or intimate partner violence who do not complain to the police - An observational
      study in Seine-Saint-Denis, France].
AB  - OBJECTIVES: to identify characteristics of victims of sexual assault or domestic
      violence who consulted in a Department of Forensic Medicine without a formal
      complaint to the police. METHODS: observational study (03/01/2014-08/31/2015) of
      individuals (age>15years) consulting in a Department of Forensic Medicine near
      Paris, France, after a sexual assault or domestic violence. Among the individuals
      who were examined in the department of Forensic Medicine, we compared the
      individuals who had not complained to the police to those who had complained to
      the police. RESULTS: A hundred and nine individuals have consulted without a
      prior complaint to the police, including 73 persons after domestic violence (i.e.
      4% of all persons examined with or without a complaint to the police) and 36
      persons after a sexual assault (i.e. 8% of all persons examined). Regarding
      domestic violence, the proportion of persons presenting recent traumatic injuries
      was lower among those who did not complain to the police than among those who did
      (64% vs. 78%, P=0.008). Regarding sexual violence, the persons who did not
      complain to the police were more frequently uncertain about the assault (42% vs.
      13%, P<0.001), reported more frequently a recent alcohol or drug intake (42% vs.
      26%, P=0.039) and less frequently showed extragenital traumatic injuries than the
      persons who did complain to the police (22% vs. 43%, P=0.016). CONCLUSION: the
      persons examined who had not complained to the police accounted for less than one
      in 20. The extension of the activity of a Department of Forensic Medicine to
      persons who do not want to be involved in a judicial process is not sufficient
      for the majority of victims to consult a forensic physician.

PMID- 29373283
TI  - Nature of Emotion Categories: Comment on Cowen and Keltner.
AB  - Cowen and Keltner (2017) published the latest installment in a longstanding
      debate about whether measures of emotion organize themselves into categories or
      array themselves more continuously along affective dimensions. We discuss several
      notable features of the study and suggest future studies should consider asking
      questions more directly about physical and psychological variation within emotion
      categories as well as similarities between categories.

PMID- 29373284
TI  - Erythropoietin to Enhance Recovery of Erectile Function in Men Following Radical
      Prostatectomy: The ERECT Trial.
AB  - Erythropoietin receptors have been localized to human penile tissue and
      periprostatic neurovascular bundles. ERECT is a placebo-controlled, phase 2,
      randomized trial assessing the effect of erythropoietin on recovery of erectile
      function for men undergoing radical prostatectomy for prostate cancer.

PMID- 29373285
TI  - Comparison of Outcomes Obtained After Regular Surgery Versus Live Operative
      Surgical Cases: Single-centre Experience with Green Laser Enucleation of the
      Prostate.
AB  - BACKGROUND: Live surgery remains controversial. Although it may improve surgical
      training and accelerate the dissemination of technical steps of surgical
      procedures, controversy exists regarding patient safety in live surgery.
      OBJECTIVE: To compare the perioperative outcomes of "en bloc" green laser
      enucleation of the prostate (GreenLEP) performed in workshops during live case
      demonstration (LCD) and in standard conditions (SCs). DESIGN, SETTING, AND
      PARTICIPANTS: Between June 2015 and January 2017, all consecutive patients who
      underwent GreenLEP for benign prostatic obstruction performed by a single surgeon
      were prospectively enrolled. Perioperative data and early postoperative
      complications according to Clavien-Dindo classification were collected. Workshop
      programmes started locally according to the European Association of Urology
      policy on live surgical events in June 2015 to enrol small groups of urologists
      in the GreenLEP technique. INTERVENTION: Endoscopic enucleation of the prostate
      using a GreenLight fibre. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes
      were compared between the LCD and SC groups. RESULTS AND LIMITATIONS: Of the 126
      performed procedures, 37 were performed live during 17 LCDs with a median
      attendee number of 3. The patients' baseline characteristics were similar in both
      groups. Intraoperative parameters were comparable: total energy of 62 [53; 77]
      versus 56kJ [44; 69] (p=0.068), operative time of 61 [53; 71] versus 55min [45;
      66] (p=0.1), and morcellating time of 3 [3; 5] versus 4min [2; 6] (p=0.82) in the
      LCD versus SC group. The catheterisation time (2d [1; 2]) and length of hospital
      stay (2d [2; 3]) were similar. The overall complication rate was comparable in
      the LCD (18.9%) and SC (24.7%) groups (p=0.64). Preoperative parameters
      significantly improved from baseline without any significant differences between
      the two groups. Limitations included a small number of attendees/workshop, and
      case selections were made by the surgeon himself. CONCLUSIONS: GreenLEP was safe
      and provided satisfactory functional outcomes in both conditions. From this
      preliminary study, it seems that LCD did not jeopardise the surgeon's skill or
      technique. Similar studies are required to further assess patient safety and
      outcomes associated with live surgical events. PATIENT SUMMARY: According to the
      surgeon expertise, endoscopic enucleation of the prostate performed during live
      case demonstration provided similar functional outcomes to that performed in
      standard condition and could therefore be considered a safe potential educational
      tool.

PMID- 29373287
TI  - Exporisq-HAP database: 20 years of monitoring French occupational exposure to
      polycyclic aromatic hydrocarbon mixtures and identification of exposure
      determinants.
AB  - BACKGROUND: Millions of workers are exposed to polycyclic aromatic hydrocarbons
      (PAHs), a well-known family of carcinogens, but occupational exposure data about
      PAH mixture compositions are scarce. OBJECTIVES: To provide a detailed picture of
      airborne PAH exposures encountered in the French industrial landscape over the
      previous 20 years and to identify determinants driving exposures. METHODS:
      Results from 1643 airborne samples of 16 gaseous and particulate PAHs implemented
      into the Exporisq HAP database from 1995 to 2014 were used to describe exposure
      levels and aerosol chemical composition in many industries and activities.
      Compliance of benzo[a]pyrene (BaP) levels with several existing occupational
      exposure limits for long-term exposure was assessed. RESULTS: BaP levels were
      lower than those reported in the literature, but the level and composition of PAH
      mixtures were highly variable between and within industries. Numerous exposure
      determinants (e.g., product composition, type and temperature of process,
      ventilation and confinement) were assumed to explain these differences. The
      highest levels were found in industries using products derived from coal
      (aluminum, silicon, and coke production, manufacturing of carbon products and
      foundries), with mean BaP levels up to 23 times higher than the French
      recommended value of 150 ng/m3. Forty-seven percent of the occupational
      activities exceeded this value. Conversely, exposures resulting from petroleum
      derived products were relatively low. CONCLUSIONS: As health effects depend on
      PAH levels but also on the composition of the mixture, exposure assessments must
      characterize the entire mixtures and record specific determinants to define
      homogeneous exposure groups and to accurately assess health risks.

PMID- 29373286
TI  - TRPC proteins contribute to development of diabetic retinopathy and regulate
      glyoxalase 1 activity and methylglyoxal accumulation.
AB  - OBJECTIVE: Diabetic retinopathy (DR) is induced by an accumulation of reactive
      metabolites such as ROS, RNS, and RCS species, which were reported to modulate
      the activity of cation channels of the TRPC family. In this study, we use
      Trpc1/4/5/6-/- compound knockout mice to analyze the contribution of these TRPC
      proteins to diabetic retinopathy. METHODS: We used Nanostring- and qPCR-based
      analysis to determine mRNA levels of TRPC channels in control and diabetic
      retinae and retinal cell types. Chronic hyperglycemia was induced by
      Streptozotocin (STZ) treatment. To assess the development of diabetic
      retinopathy, vasoregression, pericyte loss, and thickness of individual retinal
      layers were analyzed. Plasma and cellular methylglyoxal (MG) levels, as well as
      Glyoxalase 1 (GLO1) enzyme activity and protein expression, were measured in WT
      and Trpc1/4/5/6-/- cells or tissues. MG-evoked toxicity in cells of both
      genotypes was compared by MTT assay. RESULTS: We find that Trpc1/4/5/6-/- mice
      are protected from hyperglycemia-evoked vasoregression determined by the
      formation of acellular capillaries and pericyte drop-out. In addition,
      Trpc1/4/5/6-/- mice are resistant to the STZ-induced reduction in retinal layer
      thickness. The RCS metabolite methylglyoxal, which represents a key mediator for
      the development of diabetic retinopathy, was significantly reduced in plasma and
      red blood cells (RBCs) of STZ-treated Trpc1/4/5/6-/- mice compared to controls.
      GLO1 is the major MG detoxifying enzyme, and its activity and protein expression
      were significantly elevated in Trpc1/4/5/6-deficient cells, which led to
      significantly increased resistance to MG toxicity. GLO1 activity was also
      increased in retinal extracts from Trpc1/4/5/6-/- mice. The TRPCs investigated
      here are expressed at different levels in endothelial and glial cells of the
      retina. CONCLUSION: The protective phenotype in diabetic retinopathy observed in
      Trpc1/4/5/6-/- mice is suggestive of a predominant action of TRPCs in Muller
      cells and microglia because of their central position in the retention of a
      proper homoeostasis of the neurovascular unit.

PMID- 29373288
TI  - Variability of Outcome Reporting Following Arthroscopic Bankart Repair in
      Adolescent Athletes: A Systematic Review.
AB  - PURPOSE: To conduct a systematic review of the literature to assess the
      variability of the reporting of outcome measures after arthroscopic Bankart
      repair for traumatic anterior shoulder instability in the adolescent population.
      METHODS: A systematic review was conducted investigating all studies reporting
      outcomes after arthroscopic Bankart repair in the adolescent population. Four
      databases (Medline, EMBASE, Ovid, and Google Scholar) were screened for clinical
      studies involving the arthroscopic management of anterior shoulder instability in
      adolescents. A full-text review of eligible studies was conducted. Inclusion and
      exclusion criteria were applied to the searched studies. A quality assessment was
      completed for each included study using the Methodological Index for
      Nonrandomized Studies instrument and the Center for Evidence-Based Medicine's
      Levels of Evidence Scale. RESULTS: We identified 8 eligible studies involving 274
      patients (282 shoulders). There was considerable variation with regard to
      reported outcomes after arthroscopic Bankart repair for anterior shoulder
      instability in the adolescent population. The most common patient-reported
      outcomes included the Rowe Score (50%), Single Assessment Numeric Evaluation
      (37.5%), American Shoulder and Elbow Surgeons Shoulder Outcome Score (25%), and
      the Constant Score (25%). Clinical outcomes reported included recurrence (100%),
      return to sport (62.5%), patient satisfaction (37.5%), stability (37.5%), pain
      scores (37.5%), and range of motion (12.5%). CONCLUSIONS: There is considerable
      variation in reported clinical outcome measurements after arthroscopic Bankart
      repair for traumatic shoulder instability in the adolescent population. This
      study supports the need for standardized outcome reporting after arthroscopic
      anterior shoulder instability surgery in adolescents. LEVEL OF EVIDENCE: Level
      IV, systematic review of Level II-IV studies.

PMID- 29373289
TI  - Patient-Reported Outcomes of Capsular Repair Versus Capsulotomy in Patients
      Undergoing Hip Arthroscopy: Minimum 5-Year Follow-up-A Matched Comparison Study.
AB  - PURPOSE: To elucidate whether capsular closure during hip arthroscopy affected
      patient outcomes over midterm follow-up. METHODS: Between 2008 and 2011, data
      were prospectively collected and retrospectively reviewed on patients who
      underwent hip arthroscopy. Patients were then matched for age, gender, worker's
      compensation, body mass index, and acetabular coverage. The inclusion criteria
      were capsular repair or unrepaired capsulotomy, lateral-center edge angle >=18
      degrees , and minimum 5-year follow-up. The exclusion criteria were previous hip
      surgery or conditions and Tonnis grade >1. Patient-reported outcome scores (PROs)
      included modified Harris hip score (mHHS), nonarthritic hip score, hip outcome
      score sport-specific subscale, and visual analog score for pain, which were
      collected preoperatively, at 3 months, and annually thereafter. Minimal clinical
      important difference (MCID) and patient acceptable symptomatic state (PASS) for
      both groups were analyzed. Patient satisfaction was noted as well as any
      complications, secondary surgery, and conversion to arthroplasty. RESULTS:
      Minimum 5-year follow-up was available for 82.5% (287 of 348) hips that met the
      inclusion criteria and were eligible for matching. Ultimately, 65 patients who
      underwent capsular repair could be matched in a 1:1 ratio to 65 patients with
      release. Both groups had significant improvements in all mean PROs. The repair
      group had significant improvement of mean PROs, visual analog score, and patient
      satisfaction at both 2-year and minimum 5-year follow-up. The unrepaired group
      had a significant decrease in mHHS (P = .001) and patient satisfaction (P = .01)
      between 2- and 5-year follow-up. Despite decreasing mHHS in the repair group
      between 2- and 5-year follow-up, both groups met the MCID and PASS criteria with
      no significant difference between them. More patients in the release group
      required conversion to hip arthroplasty (18.5% vs 10.8%). Subgroup analysis
      considering various perioperative factors confirmed this trend. Rate of revision
      arthroscopy was the same in both groups (15.4%). Complication rate was low (4.6%
      vs 6.4%) in both groups. CONCLUSIONS: Patients undergoing hip arthroscopy and who
      have minimal or no arthritis have significant short-term improvement, whether the
      capsule is closed or left unrepaired. However, at midterm follow-up, patients who
      had unrepaired capsules had deterioration in mHHS as well as a higher rate of
      conversion to arthroplasty, even when controlling for various perioperative
      variables. Despite this, patients in both groups met the MCID and PASS criteria.
      This study suggests that routine capsular closure may lead to more consistently
      durable outcome in patients undergoing hip arthroscopy, but also that individual
      patient pathology may dictate capsular management. LEVEL OF EVIDENCE: Level III,
      retrospective comparative study.

PMID- 29373290
TI  - Clinical Outcomes of Arthroscopic Primary Repair of Proximal Anterior Cruciate
      Ligament Tears Are Maintained at Mid-term Follow-up.
AB  - PURPOSE: To assess the mid-term clinical outcomes in patients with proximal
      avulsion anterior cruciate ligament (ACL) tears undergoing arthroscopic primary
      repair with suture anchors. METHODS: The first 11 consecutive patients with
      proximal avulsion tears treated with arthroscopic primary repair were evaluated
      at mid-term (minimum 5-year) follow-up. Physical examination was performed;
      laxity examination consisting of the Lachman, pivot-shift, and anterior drawer
      tests was performed; and patients were asked to complete the Lysholm, modified
      Cincinnati, Single Assessment Numeric Evaluation, and International Knee
      Documentation Committee (IKDC) questionnaires. RESULTS: Of the 11 patients, 10
      were seen at a mean follow-up of 6.0 +/- 1.5 years (range, 4.8-9.2 years). One
      patient was lost to follow-up, in whom failure had already occurred at short-term
      follow-up. One additional patient underwent reoperation for a medial meniscus
      tear and also had a partial ACL tear; this patient was clinically stable at last
      follow-up. All patients had full range of motion. Nine patients had negative
      Lachman and negative pivot-shift examination findings (IKDC score of A), and 1
      patient had a 1A Lachman result and 1+ pivot-shift result (IKDC score of B). The
      mean Lysholm score was 96.0 +/- 4.5 (range, 88-100); modified Cincinnati score,
      95.6 +/- 7.4 (range, 80-100); Single Assessment Numeric Evaluation score, 95.4 +/
      5.4 (range, 85-100); preinjury Tegner score, 7.2 +/- 1.2 (range, 5-9);
      postoperative Tegner score, 6.6 +/- 1.8 (range, 3-9); and IKDC subjective score,
      92.3 +/- 11.3 (range, 64-100). CONCLUSIONS: The clinical outcomes of arthroscopic
      primary repair of proximal ACL tears with suture anchors are excellent and are
      maintained at mid-term follow-up in a carefully selected subset of patients with
      proximal tears and excellent tissue quality. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 29373291
TI  - Proximal Long Head Biceps Rupture: A Predictor of Rotator Cuff Pathology.
AB  - PURPOSE: To investigate whether acute rupture of the proximal long head biceps is
      a harbinger of disease of the nearby supraspinatus and subscapularis tendons.
      METHODS: A retrospective chart review from February 1, 2008, to August 31, 2016,
      was performed at our institution identifying patients who presented with an acute
      (<12-week) history of "Popeye" deformity of the distal biceps and a magnetic
      resonance imaging (MRI) of the affected shoulder. MRI images were then reviewed
      in duplicate to determine supraspinatus and subscapularis tendon tear incidence,
      size, chronicity, and depth. The association between rotator cuff status and
      acute long head biceps rupture as well as patient age, sex, smoking status, hand
      dominance, and history of diabetes mellitus or trauma was then evaluated.
      RESULTS: A total of 116 patients were included in this study (mean age: 61.9 +/-
      10.9 years). A significant proportion (n = 99; incidence: 85%) were found to have
      some degree of supraspinatus or subscapularis tendon tearing on MRI (P < .001).
      These patients were also found to be significantly older compared with those with
      an intact rotator cuff (mean age 63.3 +/- 10.7 vs 54.2 +/- 9.2; P = .001). Full
      thickness rotator cuff tears were significantly more likely to involve the
      supraspinatus as opposed to the subscapularis (incidence: 44% and 21%; P = .002).
      CONCLUSIONS: Despite the expected association of rotator cuff disease with
      increasing patient age, the results of this study also affirm the hypothesis that
      inflammation in the rotator cuff interval signaled by rupture of the long head of
      biceps is a harbinger of rotator cuff disease. Clinicians should have a high
      index of suspicion regarding concomitant anterosuperior rotator cuff pathology in
      patients presenting with acute long head of biceps rupture. Early evaluation with
      advanced imaging should be strongly considered. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 29373292
TI  - Should Acetabular Retroversion Be Treated Arthroscopically? A Systematic Review
      of Open Versus Arthroscopic Techniques.
AB  - PURPOSE: To compare patient-reported outcomes, progression of radiographic
      arthritis, revision rates, and complications for hips with acetabular
      retroversion treated by open versus arthroscopic methods. METHODS: The PubMed and
      EMBASE databases were searched in August 2016 for literature on the open and
      arthroscopic techniques using the PRISMA (Preferred Reporting Items for
      Systematic Reviews and Meta-analyses) method. All studies published in the
      English language that focused on the surgical treatment of femoroacetabular
      impingement caused by retroversion were included. All arthroscopic procedures,
      such as acetabuloplasty and labral repair, and open procedures, including
      anteverting periacetabular osteotomy and surgical dislocation with osteoplasty,
      were included. Articles that did not describe how retroversion was defined were
      excluded, as were studies with less than 6 months' follow-up and fewer than 5
      patients. Two authors screened the results and selected articles for this review
      based on the inclusion and exclusion criteria. All results were scored using the
      Methodological Index for Non-randomized Studies (MINORS) criteria. RESULTS: There
      were 386 results returned and 15 articles that met the inclusion criteria of this
      study. Among the studies, 11 reviewed arthroscopic techniques and 4 reviewed open
      surgical procedures. Both techniques yield good results based on patient-reported
      outcomes with minimal progression of osteoarthritis and low complication rates.
      CONCLUSIONS: This review showed statistically and clinically significant
      improvements for the treatment of acetabular retroversion based on patient
      reported outcomes, with low progression of radiographic arthritis, revision
      rates, and complications using both open and arthroscopic methods. LEVEL OF
      EVIDENCE: Level IV, systematic review of Level I to IV studies.

PMID- 29373293
TI  - Biceps Autograft Augmentation for Rotator Cuff Repair: A Systematic Review.
AB  - PURPOSE: To improve surgical outcomes in patients with massive cuff defects,
      different techniques and augmentations are proposed. The biceps tendon is easily
      available as an autograft. Our aim was to conduct a qualitative systematic review
      of various methods and surgical techniques that use a biceps autograft (BAG) for
      rotator cuff repair. Functional outcomes are also reported. We hypothesized that
      by using a BAG to treat massive rotator cuff tears, a more anatomic and
      biomechanical reconstruction could be achieved compared with other techniques.
      METHODS: A qualitative systematic review was conducted (MEDLINE and Embase
      databases) to inventory surgical techniques for use of a BAG for rotator cuff
      repair. The following search terms were used for MEDLINE: biceps AND (augment* OR
      autograft* OR transplantation* OR (cuff AND graft*) OR biceps-incorporat*).
      Studies were included if the following criteria were fulfilled: description of
      surgical technique, only human subjects, functional outcomes noted, all study
      designs except technical notes, and no restrictions on study date. The quality of
      the studies was assessed in a standardized manner using a tool based on the
      Cochrane handbook. RESULTS: We identified 981 studies; among these, 8 case series
      met the inclusion criteria. We identified 6 studies as high quality and 2 as
      medium quality. Different techniques for harvest and augmentation were used. Some
      studies left the proximal or distal portion intact, whereas others used it as a
      free graft. The clinical results of these studies showed significantly improved
      function, pain relief, and range of motion at follow-up, although this was not
      compared with a control group. The constructs were intact on magnetic resonance
      imaging in most patients (82%) within 2 years. CONCLUSIONS: It can be concluded
      that use of a BAG is an option for augmentation in massive rotator cuff tears,
      although no definitive recommendations can be given. This is based on Level IV
      medium- and high-quality studies. LEVEL OF EVIDENCE: Level IV, systematic review
      of Level IV studies.

PMID- 29373294
TI  - Propionibacterium acnes Suture Contamination in Arthroscopic Rotator Cuff Repair:
      A Prospective Randomized Study.
AB  - PURPOSE: To examine the contamination rate of the anchor-suture and to determine
      the efficacy of 2 different surgical skin preparation solutions with or without a
      plastic adhesive drape from suture contamination in arthroscopic rotator cuff
      repair. METHODS: A prospective randomized study was undertaken to evaluate 126
      consecutive patients undergoing arthroscopic rotator cuff repair. Each shoulder
      was prepared with one of 2 randomly selected solutions according to an assigned
      envelope that indicated the procedure to be used: chlorhexidine-alcohol (1%
      chlorhexidine gluconate and 70% isopropyl alcohol) or povidone-iodine. Then, each
      group was further divided according to the usage of a plastic drape. The first
      cut-tails of the anchor-suture after cuff fixation were submitted to aerobic and
      anaerobic cultures. RESULTS: The overall rate of Propionibacterium acnes-positive
      cultures was 47% (14 of 31 cases) in the povidone-iodine group, 33% (11 of 33
      cases) in the povidone-iodine with a drape group, 33% (10 of 30 cases) in the
      chlorhexidine-alcohol group, and 9.3% (3 of 32 cases) in the chlorhexidine
      alcohol with a drape group. The positive culture rate in the chlorhexidine
      alcohol with a drape group was lower than that in the povidone-iodine group
      (relative risk, 0.2; 95% confidence interval: 0.064-0.63; number needed to treat,
      2.7; P < .0001). Coagulase-negative staphylococci were isolated in the povidone
      iodine with a drape (1 case) and chlorhexidine-alcohol with a drape group (2
      cases). No other bacteria were isolated, and no infections occurred in any of the
      patients treated in this study during the minimum 12-month follow-up period.
      CONCLUSIONS: Chlorhexidine-alcohol solution with an adhesive plastic drape was
      more effective than chlorhexidine-alcohol without a plastic drape and povidone
      iodine with/without a plastic drape in eliminating P acnes suture contamination.
      However, the usage of a plastic drape slightly increased the risk of coagulase
      negative Staphylococcus proliferation. LEVEL OF EVIDENCE: Level I, therapeutic,
      prospective, randomized trial.

PMID- 29373295
TI  - The Correlation Between Arthroscopically Defined Acetabular Cartilage Defects and
      a Proposed Preoperative Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of
      Cartilage Index in Hips of Patients With Femoroacetabular Impingement Syndrome.
AB  - PURPOSE: To evaluate a delayed gadolinium-enhanced magnetic resonance imaging of
      cartilage (dGEMRIC) index designed to predict focal acetabular articular
      cartilage damage in patients with femoroacetabular impingement (FAI). METHODS:
      The inclusion criteria were patients who underwent dGEMRIC and hip arthroscopy
      between April 2010 and August 2015 for FAI syndrome. The exclusion criteria were
      previous hip conditions, a Tonnis grade greater than 1, and a delay between
      magnetic resonance imaging and surgery greater than 180 days. The cutoff value
      for full-thickness chondral damage was set to 350 milliseconds. The coronal
      anterolateral (CAL) index was designed to evaluate focal articular anterolateral
      chondral defects. We calculated the binary classification test of the CAL index
      for full-thickness chondral damage, with arthroscopy as the gold standard. We
      calculated the correlation between the CAL index and the arthroscopically defined
      acetabular labrum articular disruption (ALAD) and Outerbridge grades and tested
      for differences between no or mild focal chondral damage and moderate or severe
      focal chondral damage. We repeated this analysis on the sagittal superior index,
      a combination of the sagittal anterior and posterior indices. RESULTS: A total of
      195 hips (183 patients) were reviewed. The CAL index showed a sensitivity of 55%
      (95% confidence interval [CI], 32%-76%), specificity of 81% (95% CI, 74%-86%),
      positive predictive value of 27% (95% CI, 18%-37%), and negative predictive value
      of 93% (95% CI, 90%-96%). The CAL index showed a significant difference between
      no or mild focal chondral damage and moderate or severe focal chondral damage per
      both ALAD and Outerbridge groups (P < .0001). The CAL index was moderately
      inversely correlated with ALAD and Outerbridge grades (rho = -0.403, P < .0001).
      The sagittal superior index was not significantly different between the groups
      and showed a weak correlation with focal defects. CONCLUSIONS: The CAL index may
      play a role in ruling out full-thickness articular cartilage defects in patients
      with FAI syndrome. In addition, it may help in differentiating between no or mild
      focal chondral damage and moderate or severe focal chondral damage. LEVEL OF
      EVIDENCE: Level III, case-control study.

PMID- 29373296
TI  - Acetabular All-Suture Anchor for Labral Repair: Incidence of Intraoperative
      Failure due to Pullout.
AB  - PURPOSE: To report on the incidence and features of intraoperative anchor pullout
      in a consecutive series of patients undergoing arthroscopic labral repair of the
      hip. METHODS: Over an 18-month period, 434 consecutive cases underwent labral
      repair by a single surgeon with a particular anchor system. The following data
      were recorded: (1) age and gender of all cases; (2) number of anchors used; (3)
      number of cases in which intraoperative anchor failure occurred; (4) number of
      anchors that failed; and (5) age and gender of those cases in which anchor
      failure occurred. Failures were reported for 3-month intervals. One patient
      underwent repair with an alternative anchor system during this time period and
      was excluded. RESULTS: Mean age was 34.2 (14-71) years with 180 males and 254
      females. A total of 2,007 anchors were used, averaging 4.6 per case (1-8). Thirty
      three anchors pulled out among 30 patients, representing a 1.6% incidence among
      all anchors. Mean age among pullouts was 37.8 (17-54) years with 11 males and 19
      females. There was no difference compared with patient population in which no
      anchor pulled: mean 33.9 (14-71) years (P = .085) with 169 males and 235 females
      (P = .578). Pullouts were evenly distributed over the 3-month intervals (4, 4, 6,
      6, 5, 8). Pullout was mostly due to failure to securely imbed the anchor in bone.
      Only 2 were known to pull out in the presence of being securely seated in bone.
      CONCLUSIONS: These data support that the security of this particular all-suture
      anchor at implantation is exceptionally reliable for a single experienced
      surgeon, and there is no demonstrable learning curve. LEVEL OF EVIDENCE: Level
      IV, retrospective review of a case series.

PMID- 29373297
TI  - Humeral Retroversion and Capsule Thickening in the Overhead Throwing Athlete: A
      Systematic Review.
AB  - PURPOSE: To investigate the humeral and soft-tissue adaptations, including
      humeral retroversion, range of motion, and posterior capsule changes, in overhead
      throwing athletes. METHODS: We performed a systematic review in accordance with
      Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)
      guidelines. PubMed, MEDLINE, CENTRAL (Cochrane Central Register of Controlled
      Trials), and Embase were searched from January 1, 2011, through April 23, 2017,
      by 2 reviewers independently and in duplicate. The methodologic quality of all
      included articles was assessed using the Methodological Index for Non-randomized
      Studies criteria. Interobserver agreement for assessments of eligibility was
      calculated with the Cohen kappa statistic. Descriptive statistics and raw counts
      were used to summarize data. RESULTS: We identified 14 studies (6 Level IV and 8
      Level III) including 1,152 overhead throwing athletes. The mean age of the
      included athletes was 18.37 years (standard deviation, 1.52 years), with 59% of
      the athletes being pitchers and 41% being position players. Significantly greater
      humeral retroversion was found across all studies evaluating bony morphology in
      the dominant arm of overhead throwing athletes (range of mean differences, 9.6
      degrees -25.8 degrees ). Each of these studies also found decreased internal
      rotation in the dominant arm (range of mean internal rotation differences, -28
      degrees  to -7.8 degrees ). Five studies found a significant negative correlation
      between the difference in humeral retroversion between the 2 arms and the
      difference in internal rotation (range of Pearson correlation coefficients, -0.56
      to -0.35). Soft-tissue adaptations were assessed in 5 studies, with 4 identifying
      significantly thicker posterior capsules and 2 identifying significantly stiffer
      posterior capsules (P < .05). CONCLUSIONS: Overhead throwing athletes
      consistently show several distinct changes in their dominant shoulder. These
      include increased humeral retroversion and the presence of a thickened and stiff
      posterior capsule. Concomitantly, there is often reduced internal rotation and
      increased external rotation of the dominant arm. LEVEL OF EVIDENCE: Level IV,
      systematic review of Level III and IV studies.

PMID- 29373298
TI  - Patient Reported Outcomes Measurement Information System Scores Are Responsive to
      Early Changes in Patient Outcomes Following Arthroscopic Partial Meniscectomy.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that Patient
      Reported Outcomes Measurement Information System (PROMIS) computer-adaptive
      testing (CAT) physical function and pain interference scores can detect early
      variations in postoperative outcomes following arthroscopic partial meniscectomy
      and to determine whether age, sex, body mass index, mechanical symptoms, duration
      of symptoms, and the severity of chondrosis affect these scores. METHODS: Seventy
      five patients who had undergone a partial meniscectomy between September 2015 and
      March 2016 and had both preoperative and postoperative PROMIS-CAT data for
      physical function, pain interference, and depression were included. Demographic,
      clinical, and surgical data including the presence of intraoperative chondral
      lesions were collected for statistical analysis to assess for factors that led to
      differences in PROMIS-CAT outcomes. RESULTS: Preoperatively, patients had
      decreased physical function and increased pain interference in excess of 1
      standard deviation from the general population with mean PROMIS scores of 38.5
      and 63.5, respectively. At the 6-week postoperative visit, patients had
      significant improvements in both physical function and pain interference with
      mean scores of 43.4 (P < .001, SE = 0.75) and 55.5 (P < .001, SE = 0.83). Female
      patients had less improvement in PROMIS physical function (P = .03) and
      depression (P = .02) scores postoperatively compared with male patients. Patients
      with high-grade articular cartilage lesions had less improvement in physical
      function (P = .014) and pain interference (P = .010) at 6 weeks postoperative
      compared with patients with low grade or no chondral lesion. CONCLUSIONS: PROMIS
      CAT provides responsive outcome measures to early postoperative changes in
      physical function and pain following arthroscopic partial meniscectomy and has
      prognostic value in patient outcomes 6 weeks after procedure. LEVEL OF EVIDENCE:
      Level IV case series.

PMID- 29373299
TI  - Post-operative delayed elevation of ALT correlates with early death in patients
      with HBV-related hepatocellular carcinoma and Post-hepatectomy Liver Failure.
AB  - BACKGROUND: Post-hepatectomy Liver Failure (PHLF) remains the primary cause of
      perioperative death. The kinetics of transaminase levels are usually measured as
      markers of hepatocellular injury following partial hepatectomy, but their
      correlation with PHLF and post-operative mortality is unclear. The aim of study
      was to compare the post-operative transaminase kinetics with short term survival
      in those patients that developed PHLF. METHODS: A retrospective review of
      patients with HBV-related HCC and who developed PHLF was performed. Logistic
      regression analysis was conducted to analyze risk factors for postoperative
      delayed elevation of ALT (PDE-ALT) PHLF and lethal PHLF. RESULT: Of the 69
      patients who developed PHLF 36 (52%) died. In those patients who died the mean +/
      SD ALT and AST rose from day (POD) 1-3 and continued to fluctuate with highly
      abnormal levels beyond day 3 with a mean +/- SD peak ALT level beyond POD 3 of
      1851 +/- 1644 U/L (p < 0.001). CONCLUSIONS: The kinetics of the post-operative
      transaminases were significantly correlated with perioperative mortality in those
      patients who developed PHLF. PDE-ALT indicates an increased risk of death in HBV
      related HCC patients with PHLF.

PMID- 29373300
TI  - "The Filter is Kind of Broken": Family Caregivers' Attributions About Behavioral
      and Psychological Symptoms of Dementia.
AB  - OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are common,
      often challenging to manage, and may erode caregivers' well-being. Few studies
      have explored caregivers' perspectives of what causes these behaviors, but such
      attributions may be important-particularly if they negatively impact the care
      dyad. This study examined causal attributions about BPSD among individuals caring
      for a family member with dementia. DESIGN: In-depth qualitative data were
      obtained from family caregivers of older adults with dementia. SETTING: As part
      of a larger study (NINR R01NR014200), four focus groups were conducted with
      caregivers by an experienced facilitator. PARTICIPANTS: A total of 26 family
      caregivers participated in the four focus groups. MEASUREMENTS: Caregivers
      reported their own attributions about the causes of their care recipient's BPSD.
      Sessions were audio-recorded. Data were transcribed, coded to determine relevant
      concepts, and reduced to identify major categories. RESULTS: Five categories were
      determined. Caregivers attributed BPSD to: 1) neurobiological disease factors; 2)
      physical symptoms or comorbid health conditions; 3) psychological reactions to
      dementia; 4) shifting social roles and relationships following dementia onset;
      and 5) environmental changes such as lack of routine and medical transitions
      (e.g., hospitalization). Despite this seemingly multifactorial attribution to
      BPSD etiology, a number of respondents also indicated that BPSD were at least
      partly within the care recipient's control. CONCLUSIONS: Family caregivers
      attribute BPSD to a range of care recipient and environmental factors.
      Caregivers' own causal beliefs about BPSD may reflect unmet educational needs
      that should be considered in the development of targeted interventions to
      minimize caregiving stress.

PMID- 29373301
TI  - Conceptual distortions of hand structure are robust to changes in stimulus
      information.
AB  - Previous studies showed stereotyped distortions in hand representations. People
      judge their knuckles as farther forward in the hand than they actually are. The
      cause of this bias remains unclear. We tested whether both visual and tactile
      information contribute to the bias. In Experiment 1, participants judged the
      location of their knuckles by pointing to the location on their palm with: (1) a
      metal baton (using vision and touch), (2) a metal baton while blindfolded (using
      touch), or (3) a laser pointer (using vision). Distal mislocalisations were found
      in all conditions. In Experiment 2, we investigated whether judgments are
      influenced by visual landmarks such as creases. Participants localized their
      knuckles on either a photograph of their palm or a silhouette. Distal
      mislocalisations were apparent in both conditions. These results show that distal
      biases are resistant to changes in stimulus information, suggesting that such
      mislocalisations reflect a conceptual mis-representation of hand structure.

PMID- 29373302
TI  - When is cognitive penetration a plausible explanation?
AB  - Albert Newen and Petra Vetter argue that neurophysiological considerations and
      psychophysical studies provide striking evidence for cognitive penetration. This
      commentary focuses mainly on the neurophysiological considerations, which have
      thus far remained largely absent in the philosophical debate concerning cognitive
      penetration, and on the cognitive penetration of perceptual experiences, which is
      the form of cognitive penetration philosophers have debated about the most. It is
      argued that Newen and Vetter's evidence for cognitive penetration is unpersuasive
      because they do not sufficiently scrutinize the details of the empirical studies
      they make use of-the details of the empirical studies are crucial also when the
      studies are used in philosophical debates. The previous does not mean that
      cognitive penetration could not occur. Quite the contrary, details of the
      feedback connections to the visual perceptual module and one of the candidates
      presented by Newen and Vetter suggest that cognitive penetration can occur in
      rare cases.

PMID- 29373303
TI  - First fruits of the RO-ILS system: Are we learning anything new?

PMID- 29373304
TI  - Epidemiology of type 1 diabetes in Asturias: 2002-2011.
AB  - INTRODUCTION: Type 1 diabetes mellitus (T1DM) is one of the most common chronic
      diseases in childhood. An increased incidence of T1DM has recently been noted in
      children under 15 years of age, and especially in the younger group. The purpose
      of this study was to know the incidence of T1DM in Asturias and its
      characteristics. MATERIAL AND METHODS: Children and young adults under 40 years
      of age living in Asturias and diagnosed with T1DM in public and private centers
      from January 1, 2002 to December 31, 2011, were included in the study.
      Information collected included age, sex, date of diagnosis, initial symptoms, and
      biochemical parameters of the disease. RESULTS: A total of 436 patients were
      diagnosed, of whom 59.63% were males; 169 were younger than 15 years, 56.8% of
      them males. The age-adjusted overall incidence rate (IR) in Asturias of people
      diagnosed with diabetes before 40 years of age during this period was
      9.45/100.000 population/year (95% CI: 8.58-10.38), 11.07 in males (95% CI: 9.77
      12.50) and 7.77 in females (95% CI: 6,66-9,00). In subjects under 30 years of
      age, IR rate was 10.82 (95% CI: 9.67-12.07), 11.91 in males (95% CI: 10.23-13.78)
      and 7.61 in females (95% CI: 6,25-9.17). The IR in subjects younger than 15 years
      of age was 15.60 (95% CI: 13.33-18.13), 17.24/100,000 population/year (95% CI:
      13.97-21.06) in males and 13, 86 (95% CI: 10.86-17.42) in females. Estimated IR
      adjusted by age group in children under 15 years of age was 9.58 (95% CI: 6.64
      13.39) in those aged 0-4 years, 18.25 in those aged 5-9 years (95% CI: 14.06
      23.31), and 18.78 (95% CI: 14.67-23.69) between 10 and 14 years of age. IR
      remained stable in virtually all age groups and in both sexes, except in girls
      under 4 years of age, who showed a significant upward trend. There were
      significant differences in incidence between the central area of Asturias,
      predominantly urban, and the peripheral areas, mainly devoted to farming and
      livestock breeding. Thus, while IR in Mieres was 8/100,000/year, in Jarrio
      reached 25.6/100,000/year. CONCLUSION: In Asturias, incidence of T1DM in children
      and young adults is similar to that of the surrounding communities, but lower
      than the average in Spain. It has remained stable in recent years, except in the
      younger girls (in whom it has increased), and shows a great geographical
      variability between the center of the region and the periphery.

PMID- 29373305
TI  - First detection of tick-borne encephalitis virus RNA in clinical specimens of
      acutely ill patients in Hungary.
AB  - Tick-borne encephalitis virus (TBEV) is one of the endemic flaviviruses in
      Hungary, which is responsible for human infections every year. Neurological
      involvement in the disease is characterized by meningitis, encephalitis or
      meningoencephalitis which can result in long-term neurological and
      neuropsychiatric sequelae. Microbiological diagnosis of acute cases is
      predominantly based on serological tests due to the limited duration of viremia
      and long incubation period, however, the application of molecular methods can
      also supplement the serological diagnosis and provides epidemiological data. The
      aim of this study was to determine how viral RNA could successfully be detected
      from different body fluids of serologically confirmed acute cases. Serum, whole
      blood, cerebrospinal fluid and urine samples of 18 patients from the total of the
      19 serologically diagnosed cases were investigated by using the RT-PCR method.
      Two sera and one urine sample of three patients tested positive and the European
      subtype of TBEV could be identified. As far as we know this was the first time
      that TBEV RNA could be detected from human clinical samples in Hungary. Our
      finding highlights that the application of molecular methods besides serological
      tests can be a valuable tool in differential diagnosis especially in areas like
      Hungary, where two or more flaviviruses are co-circulating.

PMID- 29373306
TI  - Isolated populations of Ixodes lividus ticks in the Czech Republic and Belgium
      host genetically homogeneous Rickettsia vini.
AB  - In the last two decades, the advent of molecular methods has revealed a
      remarkable diversity of rickettsiae (Rickettsiales: Rickettsiaceae) in
      invertebrates. Several species of these obligate intracellular bacteria are known
      to cause human infections, hence more attention has been directed towards human
      biting ectoparasites. A spotted fever group Rickettsia sp. was previously
      detected in Ixodes lividus ticks (Ixodidae) associated with sand martins
      (Hirundinidae: Riparia riparia). In order to identify whether this rickettsia
      varies among isolated tick populations, a total of 1758 I. lividus ticks and five
      Ixodes ricinus ticks (Ixodidae) were collected in the Czech Republic and 148 I.
      lividus ticks were collected in Belgium, from nests of sand martins, European bee
      eaters (Meropidae: Merops apiaster), Eurasian tree sparrows (Passeridae: Passer
      montanus), and from captured sand martins. We screened 165 and 78 I. lividus
      ticks (from the Czech Republic and Belgium, respectively) and all five I. ricinus
      ticks for the presence of rickettsial DNA. Only I. lividus samples were positive
      for Rickettsia vini, a spotted fever group rickettsia that commonly infects the
      tree-hole tick Ixodes arboricola (Ixodidae). Maximum likelihood analysis of the
      rickettsial sequences showed that the most closely related organism to R. vini
      corresponds to an uncharacterized rickettsia detected in Argas lagenoplastis
      (Argasidae), a nidicolous soft tick of the fairy martin (Hirundinidae:
      Petrochelidon ariel) in Australia. The observed variability of R. vini sequences
      from isolated tick populations was low; all 85 sequenced samples were identical
      to each other in five out of six partial rickettsial genes, except for the sca4
      sequence (99.9% identity, 808/809 nt) that differed in I. lividus ticks from two
      sampling sites in the Czech Republic.

PMID- 29373307
TI  - Bacterial communities adapted to higher external resistance can reduce the onset
      potential of anode in microbial fuel cells.
AB  - We investigated how bacterial communities adapted to external resistances and
      exhibited the performance of electricity production in microbial fuel cells
      (MFCs) with external resistance of 10 Omega (LR-MFC) and 1000 Omega (HR-MFC). The
      HR-MFC exhibited better performance than the LR-MFC. The power densities of the
      LR-MFC and the HR-MFC were 5.2 +/- 1.6 mW m-2 and 28 +/- 9.6 mW m-2 after day
      197, respectively. Low-scan cyclic voltammetry analyses indicated that the onset
      potential of the HR-MFC was more negative than that of the LR-MFC, suggesting
      that the higher external resistance led to enrichment of the highly current
      producing bacteria on the anode surface. All clones of Geobacter retrieved from
      the LR-MFC and the HR-MFC were members of the Geobacter metallireducens clade.
      Although the population density of Geobacter decreased from days 366-427 in the
      HR-MFC, the current density was almost maintained. Multidimensional scaling
      analyses based on denaturing gradient gel electrophoresis profiles indicated that
      the dynamics of the biofilm and anolytic communities changed synchronously in the
      two MFCs, but the dynamics of the bacterial communities in the LR-MFC and the HR
      MFC were different from each other, reflecting different processes in adaptation
      to the different external resistances. The results suggest that the microbial
      community structure was formed by adapting to higher external resistance,
      exhibiting more negative onset potential and higher performance of the HR-MFC
      through collaborating with anode-respiring bacteria and fermenters.

PMID- 29373308
TI  - Effect of inoculum size on single-cell oil production from glucose and xylose
      using oleaginous yeast Lipomyces starkeyi.
AB  - Oleaginous microbes can convert substrates such as carbon dioxide, sugars, and
      organic acids to single-cell oils (SCOs). Among the oleaginous microorganisms,
      Lipomyces starkeyi is a particularly well-suited host given its impressive native
      abilities, including the capability to utilize a wide variety of carbon sources.
      In this work, the potential of L. starkeyi NBRC10381 to produce SCOs in a
      synthetically nitrogen-limited mineral medium (-NMM) was investigated by
      differing the inoculum size using glucose and/or xylose as a carbon source.
      Fermentation using glucose and xylose as mixed carbon sources generated the
      highest production of biomass at 40.8 g/L, and achieved a lipid content of 84.9%
      (w/w). When either glucose or xylose was used separately, the totals for achieved
      lipid content were 79.6% (w/w) and 85.1% (w/w), respectively. However, biomass
      production was higher for glucose than for xylose (30.3 vs. 28.7 g/L,
      respectively). This study describes the first simultaneous achievement of higher
      levels of cell mass and lipid production using glucose and/or xylose as the
      carbon sources in different inoculum sizes.

PMID- 29373309
TI  - Metabolic dependent and independent pH-drop shuts down VirSR quorum sensing in
      Clostridium perfringens.
AB  - Clostridium perfringens produces various exotoxins and enzymes that cause food
      poisoning and gas gangrene. The genes involved in virulence are regulated by the
      agr-like quorum sensing (QS) system, which consists of a QS signal synthesis
      system and a VirSR two-component regulatory system (VirSR TCS) which is a global
      regulatory system composed of signal sensor kinase (VirS) and response regulator
      (VirR). We found that the perfringolysin O gene (pfoA) was transiently expressed
      during mid-log phase of bacterial growth; its expression was rapidly shut down
      thereafter, suggesting the existence of a self-quorum quenching (sQQ) system. The
      sQQ system was induced by the addition of stationary phase culture supernatant
      (SPCS). Activity of the sQQ system was heat stable, and was present following
      filtration through the ultrafiltration membrane, suggesting that small molecules
      acted as sQQ agents. In addition, sQQ was also induced by pure acetic and butyric
      acids at concentrations equivalent to those in the stationary phase culture,
      suggesting that organic acids produced by C. perfringens were involved in sQQ. In
      pH-controlled batch culture, sQQ was greatly diminished; expression level of pfoA
      extended to late-log growth phase, and was eventually increased by one order of
      magnitude. Furthermore, hydrochloric acid induced sQQ at the same pH as was used
      in organic acids. SPCS also suppressed the expression of genes regulated by VirSR
      TCS. Overall, the expression of virulence factors of C. perfringens was
      downregulated by the sQQ system, which was mediated by primary acidic metabolites
      and acidic environments. This suggested the possibility of pH-controlled anti
      virulence strategies.

PMID- 29373310
TI  - [Obstetrical follow-up and perinatal prognosis in drug addict pregnant women].
AB  - OBJECTIVE: To identify the factors associated with a good obstetric follow-up and
      a good perinatal prognosis, in order to adapt the management of pregnant women
      with addiction to opiates. METHODS: A retrospective study was carried out in our
      maternity between January 2012 and December 2014, including 104 women who were
      addicted to opiates, whether or not they were substituted, with or without
      associated consumptions, regardless of the term of delivery beyond 22 weeks of
      amenorrhea. RESULTS: A good obstetrical follow-up was observed by 32.7% of women.
      The father's presence (OR=3.9; P=0.0113) and investment in pregnancy (OR=4.4;
      P=0.0029), as well as the desired character of the pregnancy (OR=4.5; P=0.0008)
      appeared to be associated with the quality of the observed follow-up. Preterm
      deliveries (11.8 versus 35.8%; P=0.0103), and social measures taken at the
      discharge of the newborn from the maternity (2.9 versus 24.3%, P=0.0057) were
      less frequent. A good perinatal prognosis was found for 29.8% of the cases.
      Associated consumptions <3 (OR=2.6 [1.1-6.2]; P=0.0281) confirmed by negative
      urine drug screening (OR=2.9 [1.1-7.8]; P=0.0307) were more numerous. CONCLUSION:
      Although the follow-up and the perinatal prognosis of these pregnancies have
      improved considerably in recent years, it seems necessary to further optimize
      their management.

PMID- 29373311
TI  - [How I do... sacrospinofixation following Richter technique by mini-invasive
      vaginal route].

PMID- 29373312
TI  - [Impact of the detection of small for gestational age fetuses on the neonatal
      prognosis].
AB  - OBJECTIVE: We sought to evaluate whether the antenatal identification of small
      for gestational age (SGA) fetuses could influence the neonatal and obstetric
      prognosis. METHODS: This was a retrospective cohort study. All liveborn singleton
      neonates with a birthweight<3rd centile, born>32 weeks of gestation between
      January 1, 2011 and December 31, 2012 were included. Fetuses were considered
      "suspected SGA" when the estimated fetal weight was<10th centile or when a
      diagnosis of clinical or ultrasound SGA was explicitly noted in the record.
      Obstetrical and neonatal follow-up and outcomes of suspected SGA (SGAS group) and
      non-suspected (SGANS group) were compared, with Chi2 and the Fisher exact test
      when appropriate. RESULTS: Hundred and forty-seven neonates were included. Among
      these, 54% were suspected SGA before birth. Gestational age was lower (38.5 weeks
      gestation [WG] vs. 39.6 WG, P<0.001) and there was a higher preterm birth rate in
      the SGAS group (10% vs. 0%, P=0.005). The rate of elective cesarean sections (17%
      vs. 3%, P=0.005) was higher in the SGAS group, whereas the rate of nonelective
      cesarean sections was lower (20% vs. 33%, P=0.002). Neonatal morbidity was
      similar in both groups, as well as birth weight. CONCLUSION: SGA fetal screening
      in our cohort was associated with a higher rate of medical intervention and
      preterm birth without neonatal benefit. Nevertheless, the study's power and
      methodology are not adequate to reduce the risk of fetal death in utero or severe
      asphyxia associated with non-identification of a SGA fetus.

PMID- 29373313
TI  - [In vitro fertilization versus conversion to intrauterine insemination in
      patients with poor response to controlled ovarian hyperstimulation].
AB  - In women undergoing controlled ovarian hyperstimulation (COH) for in vitro
      fertilization (IVF), a poor ovarian response, defined as three of fewer mature
      follicles, can lead to cancellation of the cycle. However, in women with at least
      one patent tube and normal semen parameters, conversion to intrauterine
      insemination (IUI) is considered an option, offering reasonable pregnancy rates
      at a lower cost and without the complications associated with oocyte retrieval.
      Studies have shown that in cycles with only one mature follicle, IVF should be
      canceled. However, in cycles with 2 or 3 mature follicles, patients have the
      choice between IVF and conversion to IUI. Some studies have shown that IVF is
      superior to IUI in such cases, whereas other reports failed to find any
      difference. Most of these studies are retrospective and limited by the presence
      of several biases and low numbers of cycles, and to this date, there is no
      consensus on the best approach. We have thus designed a multicenter, randomized
      non-inferiority study, comparing live birth rates following conversion to IUI or
      IVF in patients with 2 or 3 mature follicles in COH cycles. Nine hundred and
      forty patients will be randomized on trigger day to either IVF or conversion to
      IUI. Our study will also include a medico-economic analysis.

PMID- 29373314
TI  - CRISPR/Cas9-mediated modification of the extreme C-terminus impairs PDGF
      stimulated activity of Duox2.
AB  - Duox2 belongs to the large family of NADPH-oxidase enzymes that are implicated in
      immune response, vasoregulation, hormone synthesis, cell growth and
      differentiation via the regulated synthesis of H2O2 and reactive oxygen species.
      We and others have shown that Duox2 and H2O2 are involved in platelet-derived
      growth factor (PDGF) induced migration of fibroblasts. Now, using the CRISPR/Cas9
      mediated genome editing we demonstrate that the extreme C-terminal region of
      Duox2 is required for PDGF-stimulated activity of Duox2 and H2O2 production. We
      generated the fibroblast cells that stably co-express the wild-type or C
      terminally modified Duox2 and fluorescent H2O2 probe Hyper. We found that
      nonsense substitution of the last 23 amino acids in Duox2 results in complete
      loss of PDGF stimulation of intracellular H2O2 and fibroblast migration, yet
      these mutations have no effects on the expression of Duox2 and other NADPH
      oxidases in cells. These findings illustrate for the first time that the extreme
      C-terminus of Duox2 is required for the functional activity of the enzyme.
      Furthermore, the conservative nature of the C-terminus suggests its role for
      activity in other NADPH-oxidases.

PMID- 29373315
TI  - Pleiotropy of ABO gene: correlation of rs644234 with E-selectin and lipid levels.
AB  - BACKGROUND: The ABO gene has been widely studied and associated with many
      different diseases such as myocardial infarction and diabetes. Pleiotropic
      effects of the ABO locus have been demonstrated. Indeed it affects different
      phenotypes such as E- and P-selectins, triglycerides and total cholesterol. The
      goal of this work was to study the SNP rs644234 located in the ABO gene with
      different phenotypes related with diseases where the ABO gene has been involved.
      METHODS: We analyzed the SNP rs644234 located in the ABO gene, by performing
      association studies with different lipid phenotypes as well as with the soluble E
      selectin levels in 348 adults from the STANISLAS Family Study. RESULTS: The major
      rs644234*T allele was associated with increased levels of soluble E-selectin
      (p=8.7*10-12). According to the lipid phenotypes, the major rs644234*T allele was
      associated with decreased levels of apolipoproteins E (ApoE) (p=0.001) and low
      density lipoprotein cholesterol (LDL-C) (p=0.032) but was associated with
      increased levels of high-density lipoprotein cholesterol (HDL-C) (p=0.013). The
      association of the HDL-C was especially significant in the male individuals
      (p=0.001). CONCLUSIONS: We confirmed that ABO is a major locus for serum soluble
      E-selectin levels variability, and we also correlated this gene with different
      lipid phenotypes. Furthermore, we demonstrated that this pleiotropic effect is
      independent. This is the first time that a correlation has been made between the
      ABO gene and the ApoE levels. According to these results, the major allele of
      this polymorphism may have a protective effect when it comes to cardiovascular
      related diseases, and more specifically when it comes to the lipid phenotypes.

PMID- 29373316
TI  - Practical recommendations for managing hemolyzed samples in clinical chemistry
      testing.
AB  - We suggest here a pragmatic approach for managing results of clinical chemistry
      testing in hemolyzed samples collected from adults/older children, attempting to
      balance the need to produce quality laboratory data with clinical urgency of
      releasing test results. Automatic measurement of the hemolysis index (H-index) in
      serum or plasma is highly advisable, whilst low-quality assessment of this test
      remains less good than a visual inspection. Regarding its practical use, when the
      H-index value does not generate an analytically significant bias, results can be
      released, whilst when the value is associated with analyte variation in a range
      between analytically and clinically significant bias (i.e. variation does not
      exceed the reference change value [RCV]), results of hemolysis-sensitive tests
      can be released in association with a comment describing the direction in which
      data are potentially altered, suggesting the need to collect another sample. When
      the H-index is associated with analyte variation exceeding clinically significant
      bias (i.e. variation exceeds the RCV), results of hemolysis-sensitive tests
      should be suppressed and replaced with a comment that biased results cannot be
      released because the sample is preanalytically compromised and advising the
      recollection of another sample. If H-index values reach an even higher critical
      cut-off (i.e. H-index corresponding to a cell-free hemoglobin concentration >=10
      g/L), all laboratory data may be unreliable and should hence be suppressed and
      replaced with a comment that all data cannot be released because the sample is
      grossly hemolyzed, also suggesting the recollection of another sample. Due to
      inaccuracy and imprecision, the use of corrective formulas for adjusting data of
      hemolysis-sensitive tests is discouraged.

PMID- 29373317
TI  - Violence against Nursing Students in the Workplace: An Iranian Experience.
AB  - Background Workplace violence has a great impact on the quality of patient care
      and satisfaction. This study aimed to determine the extent of violence
      experienced by nursing students, and its predisposing factors. Methods This was a
      cross-sectional study which was conducted on 150 nursing students in teaching
      hospitals of Ardabil University of Medical Sciences. A questionnaire form was
      used for data collection. Results Participants stated they were abused physically
      (12.7%), verbally (73.3%), racial (40.7%), and sexually (5.3%). The lack of
      awareness of the population about the tasks of the nursing students (40.0%) was
      the most important risk factor for violence against them. Conclusion The violence
      against nursing students is a common problem in the workplace. It is mainly
      caused by the lack of awareness of people from the duties of the nursing
      students. Therefore, it is necessary to educate the population about the
      responsibilities of nurses and nursing students.

PMID- 29373318
TI  - Clinical follow-up data and the rate of development of precocious and rapidly
      progressive puberty in patients with premature thelarche.
AB  - BACKGROUND: We aimed to evaluate the clinical follow-up data of patients with
      premature thelarche and determine the rate of development of precocious and early
      puberty in these patients. METHODS: The charts of 158 girls with premature
      thelarche who were followed-up in our pediatric endocrinology polyclinic were
      reviewed. The patients were divided into three groups according to the age at
      onset: group 1 (0-1 month) (n=12), group 2 (1-24 months) (n=40) and group 3 (2-8
      years) (n=106). RESULTS: At admission, the mean height standard deviation score
      (SDS), body weight (BW)-SDS, body mass index (BMI) and BMI-SDS were significantly
      higher in group 3 than in group 1 and group 2. At admission, 8.8% of the patients
      were obese and 24% of the patients were overweight. The majority of patients who
      were obese and overweight were in group 3. At the end of the follow-up, thelarche
      regressed in 24.7%, persisted in 32.9%, progressed in 25.9% and had a cyclic
      pattern in 16.5% of the patients. Precocious or rapidly progressive puberty
      developed in 47 of the 158 patients (29.7%). The mean age at progression to early
      or rapidly progressive puberty was 98.1+/-17.6 months. A total of 89.3% of the
      patients who progressed to early or rapidly progressive puberty were in group 3.
      CONCLUSIONS: Precocious or rapidly progressive puberty developed in 29.7% of
      subjects with premature thelarche. As patients who developed rapidly progressive
      puberty had a higher BW-SDS and BMI-SDS than those who did not, it is suggested
      that the increase in weight could stimulate rapidly progressive puberty in cases
      with premature thelarche.

PMID- 29373319
TI  - Brain gray matter volume differences in obese youth with type 2 diabetes: a pilot
      study.
AB  - BACKGROUND: Adults with type 2 diabetes (T2D) have significantly lower gray
      matter volume (GMV) compared to healthy peers. Whether GMV differences exist in
      youth with T2D remains unclear. Thus, we compared global and regional GMV between
      obese youth with T2D with age, race and sex similar healthy controls. METHODS: In
      a cross-sectional study, 20 obese youth with T2D underwent T1-weighted brain
      magnetic resonance imaging (MRI). Comparisons were made to 20 age, race and sex
      similar controls. Differences in global and regional GMV between groups were
      identified using voxel-based morphometry (VBM). RESULTS: Youth with T2D had a
      significantly lower global GMV-to-intracranial volume ratio (0.51+/-0.02 in T2D
      vs. 0.53+/-0.02 in controls, p=0.02, Cohen's d=0.85). There were 14 regions where
      GMV was significantly lower in the T2D group, and nine of these were found in
      either the temporal or occipital lobes. There were six regions with increased GMV
      in T2D. All regional differences were significant at p<0.05 after adjusting for
      multiple comparisons. CONCLUSIONS: Results from this pilot study show obese youth
      with T2D have significantly lower global GMV and regional GMV differences, when
      compared to their age, race and sex similar peers. Future work is needed to
      determine whether these brain findings are a direct result of adolescent-onset
      T2D.

PMID- 29373320
TI  - Hypercalcemia, hyperkalemia and supraventricular tachycardia in a patient with
      subcutaneous fat necrosis.
AB  - BACKGROUND: Subcutaneous fat necrosis (SCFN) is a rare, self-limiting condition
      that has been associated with several complications including hypercalcemia. CASE
      PRESENTATION: We present the case of a 6-week-old male who presented to his
      pediatrician with a dime-sized erythematous nodule consistent with SCFN, who was
      also found to have supraventricular tachycardia (SVT). Laboratory findings
      revealed hypercalcemia and hyperkalemia. Extensive evaluation for the electrolyte
      disturbances revealed no other etiology. This case reinforces that SCFN should be
      considered in newborns with hypercalcemia of unknown etiology. Additionally, this
      case is the first to suggest a connection between SCFN and hyperkalemia.
      Electrolyte abnormalities can potentially contribute to arrhythmogenesis and may
      have triggered the arrhythmia in our patient. CONCLUSIONS: Our case highlights
      the importance of remaining vigilant in the workup of atypical rashes of the
      infant, which should include early assessment of serum electrolytes.

PMID- 29373321
TI  - Whole blood viscosity and cerebral blood flow velocities in obese hypertensive or
      obese normotensive adolescents.
AB  - BACKGROUND: Obesity affects all major organ systems and leads to increased
      morbidity and mortality. Whole blood viscosity is an important independent
      regulator of cerebral blood flow. The aim of the present study was to evaluate
      the effect of whole blood viscosity on cerebral artery blood flow velocities
      using transcranial Doppler ultrasound in pediatric patients with obesity compared
      to healthy controls and analyze the effect of whole blood viscosity and blood
      pressure status to the cerebral artery blood flow velocities. METHODS: Sixty
      patients with obesity diagnosed according to their body mass index (BMI)
      percentiles aged 13-18 years old were prospectively enrolled. They were grouped
      as hypertensive or normotensive according to their ambulatory blood pressure
      monitoring. Whole blood viscosity and middle cerebral artery velocities by
      transcranial Doppler ultrasound were studied and compared to 20 healthy same aged
      controls. RESULTS: Whole blood viscosity values in hypertensive (0.0619+/-0.0077
      poise) and normotensive (0.0607+/-0.0071 poise) groups were higher than controls
      (0.0616+/-0.0064 poise), with no significance. Middle cerebral artery blood flow
      velocities were higher in the obese hypertensive (73.9+/-15.0 cm/s) and obese
      normotensive groups (75.2+/-13.5 cm/s) than controls (66.4+/-11.5 cm/s), but with
      no statistical significance. CONCLUSIONS: Physiological changes in blood
      viscosity and changes in blood pressure did not seem to have any direct effect on
      cerebral blood flow velocities, the reason might be that the cerebral circulation
      is capable of adaptively modulating itself to changes to maintain a uniform
      cerebral blood flow.

PMID- 29373323
TI  - Art is not special: an assault on the last lines of defense against the
      naturalization of the human mind.
AB  - The assumption that human cognition requires exceptional explanations holds
      strong in some domains of behavioral and brain sciences. Scientific aesthetics in
      general, and neuroaesthetics in particular, abound with claims for art-specific
      cognitive or neural processes. This assumption fosters a conceptual structure
      disconnected from other fields and biases the sort of processes to be studied.
      More generally, assuming that art is special is to cling to the idea that some
      aspect of our species' mental constitution makes us unique, special, and
      meaningful. This assumption continues to relegate scientific aesthetics to the
      periphery of science and hampers a naturalized view of the human mind.

PMID- 29373322
TI  - The utility of body mass index as an indicator for lipid abnormalities in non
      fasting children.
AB  - BACKGROUND: Many studies have reported the association between body mass index
      (BMI) and fasting lipid profiles in children. However, little information exists
      about the screening of dyslipidemia in the non-fasted state. This study assessed
      whether BMI can predict non-fasting lipid abnormalities in children. METHODS:
      Using gender-separated analysis, 3895 boys and 3866 girls (aged 11-12 years) were
      investigated. Total cholesterol (TC), triglyceride (TG) and HDL-cholesterol (HDL
      C) were measured, and non-HDL-C (=TC-[HDL-C]) was calculated. A BMI z-score was
      employed as the weight status. Gender-specific 95th percentiles of TC, TG and non
      HDL-C were defined as "elevated", with the 5th percentiles of HDL-C defined as
      "reduced". RESULTS: TG and non-HDL-C were positively, and HDL-C was negatively
      correlated with the BMI z-score in both genders. Both obese (2<BMI z-score) and
      overweight (1<BMI z-score<=2) were associated with the risks of elevated TG, non
      HDL-C and reduced HDL-C. In both genders, a receiver operating characteristic
      curve demonstrated that the utility of predicting the above lipid abnormalities
      was moderate; the areas under the curve ranged from 0.60 to 0.70. The optimal cut
      off for the BMI z-score for predicting elevated TG, non-HDL-C and reduced HDL-C
      were 0.52, 0.55 and 0.51 in boys and 0.34, 0.38 and 0.35 in girls, respectively.
      CONCLUSIONS: The BMI could be an indicator of abnormalities of non-fasting TG,
      non-HDL-C and HDL-C in both genders.

PMID- 29373324
TI  - Effect of hysteretic and non-hysteretic negative capacitance on tunnel FETs DC
      performance.
AB  - This work experimentally demonstrates that the negative capacitance effect can be
      used to significantly improve the key figures of merit of tunnel field effect
      transistor (FET) switches. In the proposed approach, a matching condition is
      fulfilled between a trained-polycrystalline PZT capacitor and the tunnel FET
      (TFET) gate capacitance fabricated on a strained silicon-nanowire technology. We
      report a non-hysteretic switch configuration by combining a homojunction TFET and
      a negative capacitance effect booster, suitable for logic applications, for which
      the on-current is increased by a factor of 100, the transconductance by 2 orders
      of magnitude, and the low swing region is extended. The operation of a hysteretic
      negative capacitance TFET, when the matching condition for the negative
      capacitance is fulfilled only in a limited region of operation, is also reported
      and discussed. In this late case, a limited improvement in the device performance
      is observed. Overall, the paper demonstrates the main beneficial effects of
      negative capacitance on TFETs are the overdrive and transconductance
      amplification, which exactly address the most limiting performances of current
      TFETs.

PMID- 29373325
TI  - Acute Delirium in a Hypothyroid Patient Precipitated by Iodine Supplements Use.

PMID- 29373327
TI  - Salivary duct carcinoma.
AB  - PURPOSE OF REVIEW: The review puts new information on geno- and phenotype of
      salivary duct carcinoma (SDC) in the perspective of the updated 2017 WHO
      classification. RECENT FINDINGS: The proportion of SDC is increasing. This may be
      because of a true rise in incidence, but certainly to better diagnostic tests and
      changed WHO definitions. In this light, a substantial proportion of carcinoma
      expleomorphic adenoma is now attributed to the category of SDC. 'Low-grade SDC'
      and 'SDC in-situ' of the former WHO classification, are now named low-grade and
      high-grade intraductal carcinoma (IDC), respectively. Recent series quantify
      biologic aggressiveness: perineural growth, vascular invasion, and extracapsular
      extension in lymph node metastasis are each observed in two out of three patients
      with SDC. Most patients die within 3 years, but once 5-year disease-free survival
      is reached, further disease activity is exceptional. The typical molecular
      biological profile with high human epidermal growth factor receptor 2 and
      androgen receptor expression is increasingly successfully exploited in clinical
      trials for advanced SDC. SUMMARY: The aggressive SDC is increasingly diagnosed.
      Despite intensive combined surgery and radiation therapy, many patients recur,
      for whom new bullets, targeting the molecular biological mechanisms, are the
      subject of ongoing clinical trials.

PMID- 29373326
TI  - Results in Adult Cochlear Implant Recipients With Varied Asymmetric Hearing: A
      Prospective Longitudinal Study of Speech Recognition, Localization, and
      Participant Report.
AB  - OBJECTIVES: Asymmetric hearing with severe to profound hearing loss (SPHL) in one
      ear and better hearing in the other requires increased listening effort and is
      detrimental for understanding speech in noise and sound localization. Although a
      cochlear implant (CI) is the only treatment that can restore hearing to an ear
      with SPHL, current candidacy criteria often disallows this option for patients
      with asymmetric hearing. The present study aimed to evaluate longitudinal
      performance outcomes in a relatively large group of adults with asymmetric
      hearing who received a CI in the poor ear. DESIGN: Forty-seven adults with
      postlingual hearing loss participated. Test materials included objective and
      subjective measures meant to elucidate communication challenges encountered by
      those with asymmetric hearing. Test intervals included preimplant and 6 and 12
      months postimplant. Preimplant testing was completed in participants' everyday
      listening condition: bilateral hearing aids (HAs) n = 9, better ear HA n = 29,
      and no HA n = 9; postimplant, each ear was tested separately and in the bimodal
      condition. RESULTS: Group mean longitudinal results in the bimodal condition
      postimplant compared with the preimplant everyday listening condition indicated
      significantly improved sentence scores at soft levels and in noise, improved
      localization, and higher ratings of communication function by 6 months
      postimplant. Group mean, 6-month postimplant results were significantly better in
      the bimodal condition compared with either ear alone. Audibility and speech
      recognition for the poor ear alone improved significantly with a CI compared with
      preimplant. Most participants had clinically meaningful benefit on most measures.
      Contributory factors reported for traditional CI candidates also impacted results
      for this population. In general, older participants had poorer bimodal speech
      recognition in noise and localization abilities than younger participants.
      Participants with early SPHL onset had better bimodal localization than those
      with later SPHL onset, and participants with longer SPHL duration had poorer CI
      alone speech understanding in noise but not in quiet. Better ear pure-tone
      average (PTA) correlated with all speech recognition measures in the bimodal
      condition. To understand the impact of better ear hearing on bimodal performance,
      participants were grouped by better ear PTA: group 1 PTA <=40 dB HL (n = 19),
      group 2 PTA = 41 to 55 dB HL (n = 14), and group 3 PTA = 56 to 70 dB HL (n = 14).
      All groups showed bimodal benefit on speech recognition measures in quiet and in
      noise; however, only group 3 obtained benefit when noise was toward the CI ear.
      All groups showed improved localization and ratings of perceived communication.
      CONCLUSIONS: Receiving a CI for the poor ear was an effective treatment for this
      population. Improved audibility and speech recognition were evident by 6 months
      postimplant. Improvements in sound localization and self-reports of communication
      benefit were significant and not related to better ear hearing. Participants with
      more hearing in the better ear (group 1) showed less bimodal benefit but greater
      bimodal performance for speech recognition than groups 2 and 3. Test batteries
      for this population should include quality of life measures, sound localization,
      and adaptive speech recognition measures with spatially separated noise to
      capture the hearing loss deficits and treatment benefits reported by this patient
      population.

PMID- 29373328
TI  - Nature and role of surgical margins in transoral laser microsurgery for early and
      intermediate glottic cancer.
AB  - PURPOSE OF REVIEW: Summarize recent findings regarding the impact of margin
      status on oncologic outcomes and organ preservation, as well as evaluate possible
      management policies of close and positive margins after transoral laser
      microsurgery (TLM) for Tis-T2 glottic carcinomas. RECENT FINDINGS: Impact of
      margin status on survival rates remains controversial, whereas some authors found
      close and positive margins to be independent risk factors for recurrence and
      poorer survival rates, others did not find any significant variations compared
      with negative ones. A common trend can be observed in performing a watchful
      waiting policy or second look TLM in patients with close-superficial and positive
      single-superficial margins. Further treatment seems preferable in case of deep
      and positive multiple superficial margins. SUMMARY: Positive margins are present
      in up to 50% of patients treated by TLM, even though a high rate of false
      positivity, reaching 80%, has been described. Close and positive single
      superficial margins seem to be linked to higher recurrence rates compared with
      negative margins, even though watchful wait and see policy, especially when
      performed by adjunctive visual aids like Narrow Band Imaging, maintains good
      final oncological and organ preservation outcomes. Further treatments are
      required in case of deep margin positivity.

PMID- 29373329
TI  - The lysophosphatidic acid acyltransferases (acylglycerophosphate
      acyltransferases) family: one reaction, five enzymes, many roles.
AB  - PURPOSE OF REVIEW: Lysophosphatidic acid acyltransferases
      (LPAATs)/acylglycerophosphate acyltransferases (AGPATs) are a homologous group of
      enzymes that all catalyze the de novo formation of phosphatidic acid from
      lysophosphatidic acid (LPA) and a fatty acyl-CoA. This review seeks to resolve
      the apparent redundancy of LPAATs through examination of recent literature.
      RECENT FINDINGS: Recent molecular studies suggest that individual LPAAT
      homologues produce functionally distinct pools of phosphatidic acid, whereas gene
      ablation studies demonstrate unique roles despite a similar biochemical function.
      Loss of the individual enzymes not only causes diverse effects on down-stream
      lipid metabolism, which can vary even for a single enzyme from one tissue to the
      next, but also results in a wide array of physiological consequences, ranging
      from cognitive impairment, to lipodystrophy, to embryonic lethality. SUMMARY:
      LPAATs are critical mediators of cell membrane phospholipid synthesis, regulating
      the production of specific down-stream glycerophospholipid species through
      generation of distinct pools of phosphatidic acid that feed into dedicated
      biosynthetic pathways. Loss of any specific LPAAT can lead to alterations in
      cellular and organellar membrane phospholipid composition that can vary for a
      single enzyme in different tissues, with unique pathophysiological implications.

PMID- 29373330
TI  - The importance of cohort research starting early in life to understanding child
      health.
AB  - PURPOSE OF REVIEW: The current review addresses the importance of the prospective
      cohort design in large, unselected populations starting early in life for
      understanding the origins of childhood health disorders. RECENT FINDINGS: Cohort
      studies originating in healthy populations have contributed to great advances in
      health, especially in cardiovascular diseases, but have only recently been
      applied systematically to study the origins of childhood disorders. Several large
      population-based pregnancy and/or birth cohorts have been developed in different
      parts of the world, and these are beginning to contribute to better understanding
      of the underlying causes of rare but important childhood disorders, such as
      autism. The environmental influences on child health outcomes (ECHO) Program is
      distinct in leveraging and building upon 84 existing cohorts to prospectively
      investigate the role of early-life exposures and underlying biological mechanisms
      in childhood health and disease, specifically perinatal conditions, obesity,
      neurodevelopmental disorders, asthma and related pulmonary disorders as well as
      optimum child health. ECHO is expected to comprise approximately 50 000 children.
      It is the first US study of this size and scope since the US Collaborative
      Perinatal Project of 1959-1966. SUMMARY: The ECHO project represents a new
      approach to cohort studies in childhood, efficiently making use of extant cohorts
      while adding new data collection elements that should permit novel insights into
      the underlying causes of several important pediatric conditions.

PMID- 29373331
TI  - The physiology of neonatal resuscitation.
AB  - PURPOSE OF REVIEW: As the infant's physiology changes dramatically after birth,
      modern neonatal resuscitation approaches should detect and be modified in
      response to these changes. This review describes the changes in respiratory
      physiology at birth and highlights approaches that can assist these changes.
      RECENT FINDINGS: To better target assistance given to infants at birth, the
      changes in lung physiology have been classified into three phases. The first
      phase involves lung aeration. As little or no gas exchange can occur, assistance
      should focus on airway liquid clearance. During the second phase, as airway
      liquid resides in lung tissue, assistance should focus on minimizing the
      complications associated with lung edema. The third phase occurs whenever the
      liquid is cleared from the tissue and respiratory mechanics stabilize. Although
      more traditional approaches are most effective during this phase, this is not the
      case for the first two phases. Furthermore, the glottis actively adducts during
      apnea in newborns and so noninvasive respiratory support requires the infant to
      be breathing so that the glottis will open. SUMMARY: The respiratory support
      provided to infants at birth should match the infant's changing physiology during
      transition, which requires a more sophisticated approach and equipment than
      current recommendations.

PMID- 29373332
TI  - Prognostic Implications of Predischarge Assessment of Gait Speed After Hip
      Fracture Surgery.
AB  - BACKGROUND AND PURPOSES: Hip fracture represents one of the most severe injuries
      in the older adults. In long-term survivors, disability is common and walking
      ability may be considered important predictor of functional recovery. We,
      therefore, investigated whether 4-m gait speed, assessed in older persons early
      after surgical repair of hip fracture, could predict functional recovery and
      subsequent development of major clinical outcomes. METHODS: This was a
      prospective cohort study. We included adults older than 65 years, admitted to a
      community acute care hospital with hip fracture, undergoing surgical repair. As
      soon as the participant was able to stand and walk, using walking aids as needed
      but with no person's help, the 4-m walking speed was tested as the main
      predictive variable. The outcome variables included the change in the Barthel
      Index (BI) from prehospital through 1 year postoperative as a continuous variable
      and 2 dichotomous outcomes, that is, (1) a decrease in BI greater than 5 points
      in 1 year and (2) a composite endpoint, combining 5+ points BI decline, death,
      falls, institutionalization, and need for 24-hour home assistance in 1 year.
      RESULTS: Sixty-two participants (mean age = 85 years) were enrolled and
      evaluated, on average 6 days (standard error of the mean [SEM] = 0.2) after hip
      fracture surgery. Compared with prefracture (mean = 96.3; SEM = 0.9), BI
      decreased 1 month after surgery (mean = 76.5; SEM = 2.1) and recovered only
      partially at 2 (mean = 84.1; SEM = 2.2) and 12 months (mean = 87.2; SEM = 2.8). A
      predischarge value of the walking speed below the median (20.5 cm/s) predicted a
      substantial BI reduction throughout the 12 months. Furthermore, the adjusted risk
      of a decline in the functional status was reduced by 5% (odds ratio = 0.95; 95%
      confidence interval, 0.91-0.997; P = .038) and that of the combined outcome by 7%
      (odds ratio = 0.93; 95% confidence interval, 0.88-0.99; P = .013) for each
      centimeter per second of predischarge walking speed. DISCUSSION AND CONCLUSION:
      The 4-m walking speed, measured early after surgical repair of hip fracture, has
      profound long-term prognostic implications. This assessment approach might prove
      helpful in clinical decision-making on the postoperative management of older hip
      fracture persons.

PMID- 29373333
TI  - Adding sufentanil to ropivacaine in continuous thoracic paravertebral block fails
      to improve analgesia after video-assisted thoracic surgery: A randomised
      controlled trial.
AB  - BACKGROUND: The benefit of adding opioid to a local anaesthetic for continuous
      thoracic paravertebral analgesia after video-assisted thoracic surgery (VATS) is
      unclear. OBJECTIVES: To analyse the analgesic efficacy of ropivacaine and
      sufentanil in combination compared with ropivacaine alone after VATS. DESIGN: A
      randomised, double-blinded, single-centre clinical trial. SETTING: A tertiary
      university hospital between March 2010 and April 2014. PATIENTS: Ninety patients
      were recruited, two were not included leaving 88 randomised into two groups.
      Eighteen patients were excluded from analysis and 70 completed the study.
      INTERVENTION: To receive thoracic paravertebral analgesia with either 2 mg ml
      ropivacaine and 0.25 MUg ml sufentanil (ropivacaine + sufentanil group) or 2 mg
      ml ropivacaine alone (ropivacaine group) for 48 h postoperatively. Infusion rate
      was set at 0.15 ml kg h in both groups. MAIN OUTCOME MEASURES: The primary
      endpoint was the mean total amount of self-administered morphine by the patients
      in each group at 48 h postoperatively. RESULTS: The mean +/- SD total amount of
      self-administered morphine was not significantly different between groups (53.1
      +/- 27.2 mg in the ropivacaine + sufentanil group vs. 58.8 +/- 34.3 mg in the
      ropivacaine group; P = 0.72). No significant differences were found between the
      two groups in either pain scores at rest or during movement, in opioid-related
      adverse reactions, in patient satisfaction or length of hospital stay.
      CONCLUSION: Adding 0.25 MUg ml sufentanil to 2 mg ml ropivacaine in continuous
      thoracic paravertebral analgesia for VATS did not reduce morphine consumption or
      pain scores when compared with ropivacaine alone. We cannot recommend its use for
      routine clinical practice. Further studies analysing different concentrations and
      infusion rates of sufentanil are needed before a lack of efficacy can be
      confirmed. TRIAL REGISTRATION: Clinical trial registrations: EudraCT: 2009-014832
      38. ClinicalTrials.gov: NCT 01082744.

PMID- 29373334
TI  - Comparison of double intravenous vasopressor automated system using nexfin versus
      manual vasopressor bolus administration for maintenance of haemodynamic stability
      during spinal anaesthesia for caesarean delivery: A randomised double-blind
      controlled trial.
AB  - BACKGROUND: Hypotension is a common side effect of spinal anaesthesia during
      caesarean delivery and is associated with maternal and foetal adverse effects. We
      developed an updated double intravenous vasopressor automated (DIVA) system that
      administers phenylephrine or ephedrine based on continuous noninvasive
      haemodynamic monitoring using the Nexfin device. OBJECTIVE: The aim of our
      present study is to compare the performance and reliability of the DIVA system
      against Manual Vasopressor Bolus administration. DESIGN: A randomised, double
      blind controlled trial. SETTING: Single-centre, KK Women's and Children's
      Hospital, Singapore. PATIENTS: Two hundred and thirty-six healthy women
      undergoing elective caesarean delivery under spinal anaesthesia. MAIN OUTCOME
      MEASURES: The primary outcome was the incidence of maternal hypotension. The
      secondary outcome measures were reactive hypertension, total vasopressor
      requirement and maternal and neonatal outcomes. RESULTS: The DIVA group had a
      significantly lower incidence of maternal hypotension, with 39.3% (46 of 117)
      patients having any SBP reading less than 80% of baseline compared with 57.5% (65
      of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also
      had fewer hypotensive episodes than the manual vasopressor bolus group (4.67
      versus 7.77%; P < 0.0001). There was no difference in the incidence of reactive
      hypertension or the total vasopressor requirement. The DIVA group had less wobble
      in system performance. Maternal and neonatal outcomes were similar. CONCLUSION:
      The DIVA system achieved better control of maternal blood pressure after spinal
      anaesthesia than manual vasopressor bolus administration. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT02277730.

PMID- 29373335
TI  - Anterior Mandibular Lingual Defect As a Possible Cause of Near-Fatal Bleeding
      During Routine Dental Implant Surgery: A Retrospective Computed Tomography Study.
AB  - INTRODUCTION: The anterior mandible is generally regarded as a safe anatomical
      region for implant placement. However, anatomical variations may lead to severe
      intraoperative complications with potential fatal outcome. The objective of this
      study was to evaluate the anterior mandibular lingual defect (AMLD) in patients
      undergoing implant surgery. MATERIALS AND METHODS: The CT data of 338 consecutive
      dental implant patients were reformatted with appropriate software. The AMLDs
      were first identified using 3-D reconstruction and further evaluated in the
      relevant 2-D slices. RESULTS: The AMLD was present in 10.95% of patients; of
      these, 83.8% were present bilaterally. No significant differences were found
      between sex, age, or race within the investigated population with regards to the
      presence of the AMLD. CONCLUSIONS: The presence of an AMLD might be a possible
      cause of near-fatal bleeding during routine dental implant surgery. This study
      found the presence of the AMLD in a small (10.95%), but not negligible number of
      patients. To avoid possible complications, meticulous planning and the use of 3-D
      imaging are advisable before performing implant surgery in this anatomical
      region.

PMID- 29373336
TI  - Competing Flow Between Partial Circulatory Support and Native Cardiac Output: A
      Clinical Computational Fluid Dynamics Study.
AB  - Partial circulatory support is a promising concept for the treatment of heart
      failure patients. A better understanding of induced hemodynamic changes is
      essential for optimizing treatment efficacy. Computational fluid dynamics (CFD)
      is an alternative method to gain insight into flow phenomena difficult to obtain
      in vivo. In 10 patients implanted with a Circulite Synergy Micro-pump (HeartWare,
      Framingham, Massachusetts) (a continuous flow partial circulatory assist device
      connecting the left atrium to the right subclavian artery), transient CFD
      simulations were performed. Patients were divided into two groups depending on
      their cardiac output (CO; high CO group: 5.5 +/- 1.1 L/min, low CO group: 1.7 +/-
      0.7 L/min). The partial assist device provided a supporting flow of 1.5 +/- 0.8
      L/min. Support was highest at diastole and decreased during systole because of a
      collision of the blood flows from the partial assist device and the CO. Reversed
      flow counteracting the flow of the device was significantly higher for the high
      CO group (mean flow in peak systole: -2.18 +/- 1.08 vs. 0.23 +/- 0.59 L/min; p =
      0.002) showing an inverse correlation between CO and amount of reversed flow
      during peak systole (R = -0.7; p < 0.02). The flow collision lead to higher total
      pressures at the point of collision and consequently in the Circulite outflow
      graft. The CFD simulations allow quantifying hemodynamic alterations in patients
      with partial support consisting of a flow collision, thereby reducing
      effectiveness of the circulatory support. Partial support in heart failure
      patients alternates their hemodynamics not only in providing support for the
      circulation but also inducing unfavorable changes in flow patterns.

PMID- 29373337
TI  - Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A
      Pilot Study.
AB  - PURPOSE: To describe corneal innervation and trigeminal alterations in drug-naive
      patients with Parkinson disease (PD). METHODS: A case series study was conducted
      by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72,
      68, and 66, respectively). Ophthalmologic assessment included Ocular Surface
      Disease Index questionnaire, visual acuity by the logarithm of the minimum angle
      of resolution score, pupillary light reflexes, extrinsic ocular movements,
      corneal sensitivity, and slit-lamp examination. Corneal innervation parameter
      changes were evaluated in vivo using the Confoscan 4 confocal microscope, and
      they were compared with a control data set. The Heidelberg Retina Tomograph 3
      (HRT3) has been used to assess retinal alterations in our patients, if compared
      with normal range values provided by the HRT3. Moreover, 3T magnetic resonance
      imaging (MRI) analysis of water diffusion property changes of trigeminal nerves
      was performed. All data were analyzed and compared with 2 control data sets made
      by 14 age-matched controls. RESULTS: Patients with PD showed profound alterations
      of corneal innervation and of trigeminal diffusion MRI parameters, compared with
      controls. Strong differences (PD vs. controls) were found for deep nerve
      tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2
      vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with
      the normal range. Diffusion MRI showed profound changes of white matter diffusion
      properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029
      vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106).
      CONCLUSIONS: Corneal innervation changes might occur earlier in patients with PD
      than in retinal ones. Confocal corneal innervation analysis might provide
      possible early biomarkers for a better PD evaluation and for its earlier
      diagnosis.

PMID- 29373339
TI  - No Differences in Renal Function between Balanced 6% Hydroxyethyl Starch
      (130/0.4) and 5% Albumin for Volume Replacement Therapy in Patients Undergoing
      Cystectomy: A Randomized Controlled Trial: Erratum.

PMID- 29373338
TI  - Corneal Neurotization for Neurotrophic Keratopathy: Clinical Outcomes and In Vivo
      Confocal Microscopic and Histopathological Findings.
AB  - PURPOSE: To describe the long-term outcomes and in vivo confocal microscopic
      (IVCM) and histopathological findings after corneal neurotization surgery.
      METHODS: We included 2 patients who underwent corneal neurotization surgery for
      severe unilateral neurotrophic keratopathy secondary to cerebellopontine angle
      meningioma. Corneal sensation was measured using the Cochet-Bonnet esthesiometer
      (CBE) (0-60 mm). IVCM was performed using the Heidelberg HRT3 Rostock Corneal
      Module. Histopathological examination was performed on the excised corneoscleral
      disc of patient 2. RESULTS: In patient 1, corneal sensation improved from 0 mm
      preoperatively to 60 mm in all 4 quadrants by 2 years postoperatively and was
      maintained at 5 years postoperatively with identifiable subbasal and stromal
      corneal nerves on IVCM. In patient 2, corneal sensation improved from 0 mm
      preoperatively to 10 mm in 3 quadrants (9 months postoperatively) but returned to
      0 mm in all quadrants by 2 years postoperatively. IVCM failed to identify any
      subbasal and stromal corneal nerves. At 5 years postoperatively, evisceration was
      performed to ameliorate uncontrolled and persistent ocular pain and poor
      cosmesis. Histopathological examination of the excised corneoscleral disc
      confirmed the presence of normal-sized, central corneal stromal nerve fascicles
      but without direct continuity with the transplanted perilimbal nerve bundles.
      CONCLUSIONS: Our study elucidates the mechanism of corneal neurotization surgery
      at a cellular level. Although only 1 patient achieved long-term improvement in
      corneal sensation postoperatively, the findings on IVCM and histopathological
      examination suggest that partial regeneration/maintenance of corneal nerves after
      corneal neurotization surgery is likely attributed to the paracrine neurotrophic
      support, instead of direct sprouting, from the perilimbal transplanted nerve
      fascicles.

PMID- 29373340
TI  - Residual Force Enhancement Is Preserved for Conditions of Reduced Contractile
      Force.
AB  - INTRODUCTION: The isometric muscle force attained after active stretch is greater
      than that attained in a purely isometric contraction. This property is referred
      to as residual force enhancement (RFE). Because RFE is thought to be caused by a
      titin-based passive force, it should be preserved in reduced contractile force
      states. Therefore, we evaluated the magnitude of RFE in normal and reduced
      contractile force states. METHODS: Skinned fibers of rabbit psoas and soleus (N =
      60) were used in all experiments. Reduced contractile force states were induced
      (i) by using a low Ca concentration (N = 30), (ii) by adding 20 mM butanedione
      monoxime (N = 15), and (iii) by lowering the pH level (N = 15). Force enhancement
      and reference isometric tests were conducted for each condition. In the force
      enhancement tests, fibers were actively stretched from an average sarcomere
      length of 2.4 to 3.0 MUm. The isometric force attained 15 s after the end of
      stretching was used for analysis. In the isometric reference tests, fibers were
      activated isometrically at an average sarcomere length of 3.0 MUm, and the force
      at steady state was used for analysis. The absolute and relative magnitudes of
      RFE were calculated. RESULTS: The absolute RFE was the same for the normal and
      reduced contractile force states. Because the isometric reference force was
      smaller in the reduced contractile force states, the relative RFE was greater in
      the reduced contractile force than the normal states for all conditions.
      CONCLUSION: RFE was preserved in the reduced contractile force states.

PMID- 29373341
TI  - TOXIC EFFECTS OF HYDROXYCHLOROQUINE ON THE CHOROID: Evidence From Multimodal
      Imaging.
AB  - PURPOSE: To investigate the choroidal changes that occur in hydroxychloroquine
      (HCQ) retinopathy using multimodal imaging including fluorescein angiography,
      indocyanine green angiography, and optical coherence tomography (OCT) angiography
      and to correlate these changes with retinal findings obtained using OCT and
      fundus autofluorescence. METHODS: In 20 patients (n = 40 eyes) with systemic
      lupus erythematosus or rheumatoid arthritis diagnosed to have HCQ retinopathy,
      imaging modalities including swept-source OCT, fundus autofluorescence,
      fluorescein angiography, indocyanine green angiography, and OCT angiography were
      used to evaluate retinal and choroidal changes associated with retinopathy. The
      assessments included specific findings such as presence of hyperfluorescent or
      hypofluorescent lesions on angiography and signal void zones on OCT angiography,
      their frequencies, and the correlations among the retinal and choroidal findings.
      These findings were also correlated with the severity of retinopathy. Retinopathy
      progression was defined using fundus autofluorescence and OCT and correlated with
      the retinal/choroidal findings. RESULTS: Fluorescein angiography demonstrated a
      hyperfluorescent area, which reflects a defective retinal pigment epithelium,
      with multiple tiny dark spots within the area. Indocyanine green angiography
      showed a hypofluorescent area with dark spots, which was matched to the
      hypoautofluorescent area on fundus autofluorescence. Although there were no
      specific morphologic abnormalities in the choroid layers using en face choroidal
      imaging, OCT angiography demonstrated signal void areas on the choriocapillaris
      in the areas of the retinal pigment epithelium defect. Even after cessation of
      HCQ, there was progression of retinopathy in eyes with choroidal involvement,
      particularly on the area of choroidal findings. CONCLUSION: Multimodal imaging
      demonstrates choriocapillaris degeneration in eyes with HCQ retinopathy,
      particularly those with severe retinopathy. The choroidal change was associated
      with outer retinal toxicity of HCQ.

PMID- 29373343
TI  - NANN Celebrates Award Winners.

PMID- 29373342
TI  - CHORIOCAPILLARIS FLOW VOIDS IN CRYPTOCOCCAL CHOROIDITIS USING OPTICAL COHERENCE
      TOMOGRAPHY ANGIOGRAPHY.
AB  - PURPOSE: To report an unusual case of cryptococcal choroiditis and highlight the
      multimodal imaging findings, particularly the choriocapillaris flow voids using
      optical coherence tomography angiography. METHODS: Retrospective review of the
      clinical course of a single patient with cryptococcal choroiditis. RESULTS: A 69
      year-old man undergoing chemotherapy for T-cell prolymphocytic leukemia developed
      disseminated crytococcal neoformans infection. He developed bilateral
      cryptococcal choroiditis with multiple yellow-white choroidal lesion on
      fundoscopy in both eyes. Multimodal imaging of the choroidal lesions revealed
      flow voids at the level of the choriocapillaris on optical coherence tomography
      angiography that corresponded to hypocyanescent areas on indocyanine green
      angiography when registered and overlaid on the indocyanine green angiography
      images. The superficial and deep capillary plexuses were spared. CONCLUSION: This
      case illustrates that optical coherence tomography angiography was useful in
      demonstrating that the cryptococcal choroidal lesions impaired choriocapillaris
      perfusion but spared the superficial and deep retinal plexuses.

PMID- 29373344
TI  - Nursing Assessment of Intra-abdominal Hypertension and Abdominal Compartment
      Syndrome in the Neonate.
AB  - BACKGROUND: Abdominal compartment syndrome in the surgical neonate is a low
      frequency, high-risk occurrence that if overlooked is often accompanied with long
      term sequelae and sometimes death. The importance of early detection of signs and
      symptoms through expert nursing assessment cannot be overstated. PURPOSE: To
      review the components of nursing assessment as it applies to detection of
      abdominal compartment syndrome in the surgical neonate and its relationship to
      the pathophysiology. METHODS/SEARCH STRATEGY: Detailed search of the nursing and
      medical literature. IMPLICATIONS FOR PRACTICE: The purpose of this article is to
      describe the onset of abdominal compartment syndrome in the neonate. Early
      detection of this low-frequency, high-risk occurrence hinges on expert nursing
      assessment. Complications of abdominal compartment syndrome in the neonate
      involve bowel perforation, short bowel syndrome, and sometimes death. Components
      of this expert nursing assessment and its relationship to the pathophysiology of
      compartment syndrome are presented.

PMID- 29373345
TI  - Basic Knowledge of Tracheoesophageal Fistula and Esophageal Atresia.
AB  - BACKGROUND: Tracheoesophageal fistula (TEF) and esophageal atresia (EA) are rare
      anomalies in neonates. Up to 50% of neonates with TEF/EA will have Vertebral
      anomalies (V), Anal atresia (A), Cardiac anomalies (C), Tracheoesophageal fistula
      (T), Esophageal atresia (E), Renal anomalies (R), and Limb anomalies (L)
      (VACTERL) association, which has the potential to cause serious morbidity.
      PURPOSE: Timely management of the neonate can greatly impact the infant's overall
      outcome. Spreading latest evidence-based knowledge and sharing practical
      experience with clinicians across various levels of the neonatal intensive care
      unit and well-baby units have the potential to decrease the rate of morbidity and
      mortality. METHODS/SEARCH STRATEGY: PubMed, CINAHL, Cochrane Review, and Google
      Scholar were used to search key words- tracheoesophageal fistula, esophageal
      atresia, TEF/EA, VACTERL, long gap, post-operative management, NICU, pediatric
      surgery-for articles that were relevant and current. FINDINGS/RESULTS:
      Advancements in both technology and medicine have helped identify and decrease
      postsurgical complications. More understanding and clarity are needed to manage
      acid suppression and its effects in a timely way. IMPLICATIONS FOR PRACTICE:
      Knowing the clinical signs of potential TEF/EA, clinicians can initiate
      preoperative management and expedite transfer to a hospital with pediatric
      surgeons who are experts in TEF/EA management to prevent long-term morbidity.
      IMPLICATIONS FOR RESEARCH: Various methods of perioperative management exist, and
      future studies should look into standardizing perioperative care. Other areas of
      research should include acid suppression recommendation, reducing long-term
      morbidity seen in patients with TEF/EA, postoperative complications, and how we
      can safely and effectively decrease the length of time to surgery for long-gap
      atresia in neonates.

PMID- 29373346
TI  - Complex Surgical Infants Benefit From Postdischarge Telemedicine Visits.
AB  - BACKGROUND: Transition from the neonatal intensive care unit (NICU) to home is
      challenging for caregivers of complex surgical infants. A prospective,
      observational cohort pilot study using telemedicine to improve transition was
      implemented in a quaternary level IV NICU. PURPOSE: (1) To assess, identify, and
      resolve patient care concerns in the immediate postdischarge period. (2) To
      improve caregiver knowledge and care practices. DESIGN METHODS: Caregivers of
      medically complex infants participated in telemedicine visits with neonatal
      providers within 1 week of discharge. Providers reviewed infant health, equipment
      use, and outpatient follow-up. Video was used to visualize the infant, home
      environment, and care practices. Caregivers completed a postvisit satisfaction
      survey. RESULTS: Ninety-three visits were performed from May 2015 to March 2017.
      Seventy-six percent of visits were postsurgery patients. Seventy-eight
      postdischarge issues were identified: medication administration (13%),
      respiratory (19%), feeding (33%), and surgical site (35%). Fifty percent of
      caregivers reported that telemedicine visits prevented an additional call or
      visit to a clinician; 12% prompted an earlier visit (n = 93). Caregiver
      satisfaction rating was high. Median estimation of total mileage saved by
      respondents was 1755 miles. CONCLUSIONS: Postdischarge telemedicine visits with
      complex surgical NICU graduates identify clinical issues, provide caregivers with
      support, and save travel time. Advanced practice nurses are instrumental in
      patient recruitment, with patient visits, and in providing postdischarge
      continuity of care. Barriers to implementation were identified. IMPLICATION FOR
      PRACTICE AND RESEARCH: A randomized controlled study is warranted to measure the
      value of telemedicine visits for specific patient cohorts.

PMID- 29373347
TI  - What Is the Evidence for Use of a Supplemental Feeding Tube Device as an
      Alternative Supplemental Feeding Method for Breastfed Infants?
AB  - BACKGROUND: According to the Healthy People 2020 goals, the sustainability of
      breastfeeding duration rates within the United States has not been achieved. To
      increase these rates, it is important that women with breastfeeding difficulties
      receive the support needed to continue breastfeeding. When supplementation
      occurs, it is essential that the breastfeeding relationship be preserved. Various
      methods of supplementation are often recommended including use of the
      supplemental feeding tube device (SFTD). PURPOSE: The question guiding this brief
      is "What evidence exists to support the use of an SFTD as a method of
      supplementation for breastfed infants?" SEARCH STRATEGY: The PubMed and CINAHL
      databases were queried for original research published in English from 1990
      through July 2016. Search terms included "supplemental feeding tube,"
      "breastfeeding," "term infants," "premature infants," "Supplemental Nursing
      System," "Lact-aid," and "supply line." FINDINGS: Very limited research exists on
      the use of SFTDs as a method of supplementation for breastfed infants; however,
      existing research suggests that an SFTD may be useful as a supplementation method
      for breastfed infants. High-quality research is needed to evaluate the efficacy
      of using an SFTD for supporting exclusive and all breastfeeding rates.
      IMPLICATIONS FOR PRACTICE: Nurses and providers need to be educated and trained
      in the use of SFTDs as well as all supplemental feeding methods. Information on
      efficacy and SFTD use should also be included in policies related to
      breastfeeding and human milk use. IMPLICATIONS FOR RESEARCH: Further research
      should determine best methods of supplementation for breastfed infants and should
      examine differences in breastfeeding rates when using the SFTD for
      supplementation.

PMID- 29373348
TI  - 2017 ANC Reviewers.

PMID- 29373349
TI  - A Quality Improvement Initiative to Increase Scoring Consistency and Accuracy of
      the Finnegan Tool: Challenges in Obtaining Reliable Assessments of Drug
      Withdrawal in Neonatal Abstinence Syndrome.

PMID- 29373350
TI  - FOCUS ON FAMILY CAREGIVERS.

PMID- 29373351
TI  - Colorectal Cancer Awareness for Women via Facebook: A Pilot Study.
AB  - Colorectal cancer is the third leading cause of cancer death among U.S. women.
      Women report being screened for colorectal cancer less often than men, and if
      colorectal cancer screening guidelines were routinely followed, approximately 60%
      of colorectal cancer deaths could be prevented. Many colorectal cancer screening
      interventions have not used Facebook, which is the most popular social media site
      among women. Little is known about engaging women in colorectal cancer screening
      and risk reduction information using Facebook. The "Colorectal Cancer Screening
      Awareness for Women" Facebook page was created to promote colorectal cancer
      screening and risk reduction awareness among women. Facebook posts targeted women
      aged 45-64 years and highlighted colorectal cancer screening methods, guidelines,
      and colorectal cancer risk reduction strategies. Demographics and data about the
      women's interactions with the page were collected using Facebook analytics and
      analyzed. The majority of the 391 users of the Colorectal Cancer Screening
      Awareness for Women Facebook page were women aged 45-54 years (56.5%). The most
      "liked" posts were related to colorectal cancer risk reduction behaviors. In an
      effort to increase routine colorectal cancer screening and colorectal cancer risk
      reduction behaviors, gastroenterology nurses and practices should consider
      Facebook as a good method to regularly engage women in colorectal cancer
      screening and colorectal cancer risk reduction information.

PMID- 29373352
TI  - Identifying Needs in Young Adults With Inflammatory Bowel Disease: A Qualitative
      Study.
AB  - Successful transitional care for young adults entails that healthcare teams
      recognize and understand the attitudes, perspectives, and developmental maturity
      of young adults. The aim of this study was to identify the needs of young adults
      with inflammatory bowel disease. Young adults 18-30 years of age were recruited
      from the McMaster University Medical Centre adult inflammatory bowel disease
      (IBD) clinic between July 2012 and May 2013. Semistructured interviews were audio
      taped, transcribed verbatim, and coded using a constant comparative method. QSR
      NVivo10 software was used to manage the data. Twenty-one young adults, including
      15 subjects diagnosed as adolescents (younger than 18 years) and 6 subjects
      diagnosed as young adults, were interviewed. Four broad categories of needs were
      identified: psychosocial, informational, self-advocacy, and daily living needs.
      The most commonly reported needs were psychosocial and the least common were
      daily living needs. Results from this study may be used to inform clinical
      practitioners of potential needs that may be important to the overall quality of
      patient health during young adulthood. In addition, these findings may be used to
      evaluate existing transition and self-management tools to measure success of
      transition interventions more effectively.

PMID- 29373353
TI  - Illness Cognitions and Health-Related Quality of Life of Patients With
      Inflammatory Bowel Disease.
AB  - Patients' cognitions about their disease and treatment are important mediators
      between health and quality of life of patients with chronic diseases and also
      explain the occurrence of individual differences in individuals' adjustment to
      chronic disease. The aim of this study was to examine the relationship between
      illness cognitions and health-related quality of life among adult patients with
      inflammatory bowel disease. Self-report data on illness cognition and health
      related quality of life were collected from 118 people with Crohn disease or
      ulcerative colitis. Illness cognition of greater helplessness significantly
      predicted health-related quality of life in patients with inflammatory bowel
      disease. A relative contribution of acceptance and perceived benefits was not
      confirmed as a predictor of health-related quality of life. The other variables
      (type of disease, duration of disease, age, and episode of relapses) did not have
      statistical significance, except for gender. Results demonstrate that
      experiencing helplessness in relation to the disease, its treatment, and
      consequences can be generalized to patients in all areas of daily life, leading
      to deterioration in their overall psychological and physical functioning. These
      results can provide useful indicators of potential patient's adherence in
      treatment and self-management of inflammatory bowel disease.

PMID- 29373354
TI  - Predictors of Impaired Mental Health and Support Seeking in Adults With
      Inflammatory Bowel Disease: An Online Survey.
AB  - This study explored the possible factors associated with psychological distress
      in adults with inflammatory bowel disease (IBD) and also engagement in mental
      health services (MHS) in those reporting distress in a large Australian cohort.
      Participants with IBD completed an online survey assessing perceived IBD activity
      (Manitoba Index; MI), mental health status (K10), demographic details, and
      engagement with MHS for IBD-associated issues. Of 336 participants, 76.5%
      perceived themselves as having active disease over the past 6 months, and on K10
      scores, 51.8% had a mental health issue. Of participants with a mental health
      issue, only 21.3% were currently receiving mental health support. A stepwise
      logistic regression analysis correctly classified 78.7% of the status of
      receiving mental health support, with lower income (<$60,000 per annum) the only
      significant predictor. Paradoxically, the degree of psychological distress did
      not correlate with seeking mental health support. The data show that in
      individuals with ongoing symptoms attributed to active IBD, mental health issues
      are highly prevalent, with older age and higher income being additional drivers
      of mental health issues. The greater challenge, however, seems not to be
      identifying mental health issues, but in getting those in need to engage in MHS.

PMID- 29373355
TI  - Effect of Information of Patients' Coping Style on Pregastroscopy Anxiety.
AB  - Examination of the relationship between patients' coping style, pregastroscopy
      information, and anxiety associated with gastroscopy in China was the aim of this
      study. A pretest, post-test, nonrandom assignment study with a two by two design
      was conducted. One hundred forty-five patients who underwent initial gastroscopy
      without sedation were classified into 2 groups on the basis of the coping style:
      information seekers or information avoiders using the Information Subscale of the
      Krantz Health Opinion Survey (KHOS-I). All participants were given standardized
      procedural information about gastroscopy as routine care. Half of each group was
      assigned to receive additional sensory information describing what sensation they
      would experience and how to cooperate to alleviate the discomfort. State anxiety
      assessed by the State Anxiety Scale of Spielberg's State-Trait Anxiety Inventory,
      blood pressure, and pulse were measured at enrollment and before gastroscopy. The
      information seekers and avoiders who received additional sensory information
      experienced significantly less state anxiety after the intervention. In contrast,
      the information seekers and avoiders who received standardized procedural
      information maintained their preintervention state anxiety level. Most patients
      reported their preference for sensory information. In conclusion, the provision
      of sensory information could significantly reduce patients' pregastroscopy
      anxiety regardless of patients' information coping style.

PMID- 29373357
TI  - INTERVENTIONS FOR DYSPHAGIA IN ESOPHAGEAL CANCER.

PMID- 29373356
TI  - HEPATOCELLULAR CARCINOMA WITH CARDIAC CIRRHOSIS AFTER THE FONTAN PROCEDURE.

PMID- 29373358
TI  - IT'S THE LITTLE THINGS.

PMID- 29373359
TI  - Predicting Survival in Patients Treated With Extracorporeal Membrane Oxygenation
      After Myocardial Infarction.
AB  - OBJECTIVES: Acute myocardial infarction is the most common cause of cardiogenic
      shock. Although the number of patients with acute myocardial infarction
      complicated by cardiogenic shock who were treated with venoarterial
      extracorporeal membrane oxygenation increased during the last decade, detailed
      data on survival are lacking. We sought to analyze covariates that were
      independently associated with survival in this patient population and to
      externally validate the newly developed prEdictioN of Cardiogenic shock OUtcome
      foR Acute myocardial infarction patients salvaGed by venoarterial Extracorporeal
      membrane oxygenation (ENCOURAGE) score. DESIGN: Retrospective clinical study.
      SETTING: A single academic teaching hospital. PATIENTS: Adult patients with acute
      myocardial infarction complicated by cardiogenic shock who were supported by
      venoarterial extracorporeal membrane oxygenation from June 2008 to September
      2016. INTERVENTIONS: Fourteen individual variables were assessed for their
      association with the primary endpoint. These variables were prespecified by the
      study team as being the most likely to affect survival. A receiver operating
      characteristic analysis was also performed to test the ability of the ENCOURAGE
      score to predict survival in this patient cohort. MEASUREMENTS AND MAIN RESULTS:
      The primary endpoint of the study was in-hospital survival. A total of 61
      patients were included in the analysis. Thirty-seven (60.7%) could be weaned from
      venoarterial extracorporeal membrane oxygenation and 36 (59.0%) survived.
      Survival was significantly higher in patients less than 65 years old (odds ratio,
      14.6 [CI, 2.5-84.0]; p = 0.003), whose body mass index was less than 32 kg/m
      (odds ratio, 5.5 [CI, 1.2-25.4]; p = 0.029) and international normalized ratio
      was less than 2 (odds ratio, 7.3 [CI, 1.3-40.1]; p = 0.022). In patients where
      the first lactate drawn was less than 3 mmol/L, the survival was not
      significantly higher (odds ratio, 4.4 [CI, 0.6-32.6]; p = 0.147). The C-statistic
      for predicting survival using a modified version of the ENCOURAGE score, which
      replaced prothrombin activity less than 50% with an international normalized
      ratio greater than 2, was 0.74 (95% CI, 0.61-0.87). CONCLUSIONS: In this single
      center study, several important covariates were associated with improved survival
      in patients with acute myocardial infarction complicated by cardiogenic shock who
      were supported by venoarterial extracorporeal membrane oxygenation and the
      ENCOURAGE score was found to be externally valid for predicting survival to
      hospital discharge.

PMID- 29373360
TI  - Sepsis-Associated Coagulopathy Severity Predicts Hospital Mortality.
AB  - OBJECTIVES: To assess whether sepsis-associated coagulopathy predicts hospital
      mortality. DESIGN: Retrospective cohort study. SETTING: One-thousand three
      hundred beds urban academic medical center. PATIENTS: Six-thousand one-hundred
      forty-eight consecutive patients hospitalized between January 1, 2010, and
      December 31, 2015. INTERVENTIONS: Mild sepsis-associated coagulopathy was defined
      as an international normalized ratio greater than or equal to 1.2 and less than
      1.4 plus platelet count less than or equal to 150,000/uL but greater than
      100,000/uL; moderate sepsis-associated coagulopathy was defined with either an
      international normalized ratio greater than or equal to 1.4 but less than 1.6 or
      platelets less than or equal to 100,000/uL but greater than 80,000/uL; severe
      sepsis-associated coagulopathy was defined as an international normalized ratio
      greater than or equal to 1.6 and platelets less than or equal to 80,000/uL.
      MEASUREMENTS AND MAIN RESULTS: Hospital mortality increased progressively from
      25.4% in patients without sepsis-associated coagulopathy to 56.1% in patients
      with severe sepsis-associated coagulopathy. Similarly, duration of
      hospitalization and ICU care increased progressively as sepsis-associated
      coagulopathy severity increased. Multivariable analyses showed that the presence
      of sepsis-associated coagulopathy, as well as sepsis-associated coagulopathy
      severity, was independently associated with hospital mortality regardless of
      adjustments made for baseline patient characteristics, hospitalization variables,
      and the sepsis-associated coagulopathy-cancer interaction. Odds ratios ranged
      from 1.33 to 2.14 for the presence of sepsis-associated coagulopathy and from
      1.18 to 1.51 for sepsis-associated coagulopathy severity for predicting hospital
      mortality (p < 0.001 for all comparisons). CONCLUSIONS: The presence of sepsis
      associated coagulopathy identifies a group of patients with sepsis at higher risk
      for mortality. Furthermore, there is an incremental risk of mortality as the
      severity of sepsis-associated coagulopathy increases.

PMID- 29373361
TI  - Urgent Chemotherapy in Sepsis-Like Shock Related to Hematologic Malignancies.
AB  - OBJECTIVES: Hematologic malignancies may result in multiple organ involvement
      including pulmonary and renal dysfunctions, and the less common acute circulatory
      failure. We herein addressed the outcome of patients with sepsis-like shock
      related to aggressive hematologic malignancies. DESIGN: A 10-year (2007-2016)
      monocenter retrospective study. SETTINGS: A medical ICU in a tertiary care
      center. PATIENTS: Patients with circulatory shock requiring vasopressors and who
      subsequently received chemotherapy. Shock was presumably related to the
      underlying malignancy after ruling out an ongoing or new-onset infectious
      process. The extent and time course of organ failures was assessed by a modified
      Sequential Organ Failure Assessment score devoid of the platelet component.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seventeen patients were
      included, including 13 with non-Hodgkin lymphoma, two with hyperleukocytic acute
      myeloid leukemia, and two with "Human Herpes virus 8"-associated multicentric
      Castleman's disease. The following associated conditions prompted urgent
      administration of chemotherapy: tumor lysis syndrome (n = 10), hemophagocytic
      lymphohistiocytosis (n = 3), compressive bulky tumor (n = 3), pulmonary
      involvement (n = 3), and disseminated intravascular coagulation (n = 1).
      Following the initiation of chemotherapy, a number of patients died rapidly from
      untractable multiple organ failure. In contrast, chemotherapy led to a fast and
      dramatic improvement in organ failures in early survivors, as shown by the
      decrease in the modified Sequential Organ Failure Assessment score. However, the
      overall outcome was poor since only four and three patients could be discharged
      alive from the ICU and the hospital, and three and two patients remained alive at
      6 months and 1 year. CONCLUSIONS: Multiple organ dysfunction syndrome related to
      hematologic malignancies is associated with a dismal outcome. A chemotherapy
      trial may provide a fast prognostic assessment of the reversibility of organ
      failure.

PMID- 29373363
TI  - Match Situations Leading to Head Injuries in Professional Male Football (Soccer)
      A Video-based Analysis Over 12 Years.
AB  - OBJECTIVE: To identify risk situations promoting head injuries in professional
      male football (soccer) and to investigate the impact of a rule change in 2006
      punishing elbow-head contacts. DESIGN: Analysis of video sequences of head events
      leading to head injury. PARTICIPANTS: Professional football players of the first
      male German Bundesliga. MAIN OUTCOME MEASURES: Observational criteria of head
      impacts on video recordings (players' actions preceding head injuries, foul play
      referee's decision and assessment of rater, ball possession, on-pitch medical
      treatment, and consequences of head impact). RESULTS: Three hundred thirty-four
      head injuries were reported in kicker Sportmagazin corresponding to an incidence
      rate of 2.25 (95% confidence interval 2.01-2.51) per 1000 player match hours. The
      injured player predominantly jumped (60%), headed the ball (36%), or ran forwards
      (20%); the noninjured players mainly jumped (64%), headed the ball (27%), or
      raised the elbow to the head (23%). Free ball situations (2 players challenge for
      the ball) caused most of the head injuries (81%). The players' action "raising
      the elbow" during a head injury seemed to be lower after the rule change.
      CONCLUSIONS: Jumping for the ball with the intention of heading is the
      predominant action associated with head injury risk. Head injuries occur most
      often when players challenge for the ball in a header duel. As head injuries bear
      the potential risk of long-term health sequelae, the identification of
      situational circumstances is essential to develop preventative means in the
      future.

PMID- 29373364
TI  - Combined Anterolateral, Anterior, and Anteromedial Ankle Impingement in an
      Adolescent Soccer Player-A Case Report and Review of the Literature.
AB  - A unique case of combined anterolateral, anterior, and anteromedial ankle
      impingement in an adolescent soccer player is presented in this article. To the
      best of our knowledge, this is the only report of circumferential, massive,
      anterior ankle impingement in children described in the literature. The
      importance of proper diagnosis and treatment of such a lesion is illustrated in
      this case report. We also emphasize that clinical examination combined with 3D
      computed tomography scan reconstruction is an excellent and cost-effective
      imaging modality that can help with the diagnosis of anterior ankle impingement.
      Finally, open surgical treatment showed excellent results in an elite athlete.

PMID- 29373362
TI  - Acute Kidney Injury and Subsequent Frailty Status in Survivors of Critical
      Illness: A Secondary Analysis.
AB  - OBJECTIVES: Acute kidney injury frequently complicates critical illness and is
      associated with high morbidity and mortality. Frailty is common in critical
      illness survivors, but little is known about the impact of acute kidney injury.
      We examined the association of acute kidney injury and frailty within a year of
      hospital discharge in survivors of critical illness. DESIGN: Secondary analysis
      of a prospective cohort study. SETTING: Medical/surgical ICU of a U.S. tertiary
      care medical center. PATIENTS: Three hundred seventeen participants with
      respiratory failure and/or shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Acute kidney injury was determined using Kidney Disease Improving Global
      Outcomes stages. Clinical frailty status was determined using the Clinical
      Frailty Scale at 3 and 12 months following discharge. Covariates included mean
      ICU Sequential Organ Failure Assessment score and Acute Physiology and Chronic
      Health Evaluation II score as well as baseline comorbidity (i.e., Charlson
      Comorbidity Index), kidney function, and Clinical Frailty Scale score. Of 317
      patients, 243 (77%) had acute kidney injury and one in four patients with acute
      kidney injury was frail at baseline. In adjusted models, acute kidney injury
      stages 1, 2, and 3 were associated with higher frailty scores at 3 months (odds
      ratio, 1.92; 95% CI, 1.14-3.24; odds ratio, 2.40; 95% CI, 1.31-4.42; and odds
      ratio, 4.41; 95% CI, 2.20-8.82, respectively). At 12 months, a similar
      association of acute kidney injury stages 1, 2, and 3 and higher Clinical Frailty
      Scale score was noted (odds ratio, 1.87; 95% CI, 1.11-3.14; odds ratio, 1.81; 95%
      CI, 0.94-3.48; and odds ratio, 2.76; 95% CI, 1.34-5.66, respectively). In
      supplemental and sensitivity analyses, analogous patterns of association were
      observed. CONCLUSIONS: Acute kidney injury in survivors of critical illness
      predicted worse frailty status 3 and 12 months postdischarge. These findings have
      important implications on clinical decision making among acute kidney injury
      survivors and underscore the need to understand the drivers of frailty to improve
      patient-centered outcomes.

PMID- 29373365
TI  - Sarcopenia and Postoperative Complication Risk in Gastrointestinal Surgical
      Oncology: A Meta-analysis.
AB  - OBJECTIVE: The aim of the study was to evaluate sarcopenia as a predictor of
      postoperative risk of major and total complications after surgery for
      gastrointestinal cancer. BACKGROUND: Sarcopenia is associated with poor survival
      in gastrointestinal cancer patients, but the role of sarcopenia as prognostic
      tool in surgical oncology has not been established, and no consensus exists
      regarding assessment and management of sarcopenic patients. METHODS: We performed
      a systematic search for citations in EMBASE, Web of Science, and PubMed from 2004
      to January 31, 2017. Random effects meta-analyses were used to estimate the
      pooled risk ratio for postoperative complications by Clavien-Dindo grade (total
      complications: grade >=2; major complications: grade >=3) in patients with
      sarcopenia versus patients without sarcopenia. Stratified analyses were performed
      by sarcopenia criteria, cutoff level, assessment methods, study quality, cancer
      diagnosis, and "Enhanced Recovery After Surgery" care. RESULTS: Twenty-nine
      studies (n = 7176) were included with sarcopenia prevalence ranging between 12%
      and 78%. Preoperative incidence of sarcopenia was associated with increased risk
      of major complications (risk ratio 1.40; 95% confidence interval, 1.20-1.64; P <
      0.001; I = 52%) and total complications (risk ratio 1.35; 95% confidence
      interval, 1.12-1.61; P = 0.001; I = 60%). Moderate heterogeneity was found for
      both meta-analyses. Subgroup analyses showed that sarcopenia remained a
      consistent risk factor across stratification by sarcopenia criteria, assessment
      methods, study quality, and diagnoses. CONCLUSIONS: Sarcopenia was associated
      with an increased risk of complications after gastrointestinal tumor resection,
      but lack of methodological consensus hampers the interpretation and clinical
      utilization of these findings. Combining assessment of muscle mass with measures
      of physical function may increase the prognostic value and accuracy in
      preoperative risk stratification.

PMID- 29373366
TI  - Assessing the Safety of Overlapping Surgery at a Children's Hospital.
AB  - IMPORTANCE: Media reports have questioned the safety of overlapping surgical
      procedures, and national scrutiny has underscored the necessity of single-center
      evaluations of its safety; however, sample sizes are likely small. We compared
      the safety profiles of overlapping and nonoverlapping pediatric procedures at a
      single children's hospital and discussed methodological considerations of the
      evaluation. DATA AND DESIGN: Retrospective analysis of inpatient pediatric
      surgical procedures (January 2013 to September 2015) at a single pediatric
      referral center. Overlapping and nonoverlapping procedures were matched in an
      unbalanced manner (m:n) by procedure. Mixed models adjusting for Vizient
      predicted risk, case-mix, and surgeon compared inpatient mortality and length of
      stay (LOS). RESULTS: Among 315 overlapping procedures, 256 (81.3%) were matched
      to 645 nonoverlapping procedures. There were 6 deaths in all. The adjusted odds
      ratio for mortality did not differ significantly between nonoverlapping and
      overlapping procedures (adjusted odds ratio = 0.94 vs overlapping; 95% CI, 0.02
      48.5; P = 0.98). Wide confidence intervals were minimally improved with Bayesian
      methods (95% CI, 0.07-12.5). Adjusted LOS estimates were not clinically different
      by overlapping status (0.6% longer for nonoverlapping; 95% CI, 9.7% shorter to
      12.2% longer; P = 0.91). Among the 87 overlapping procedures with the greatest
      overlap (>=60 min or >=50% of operative duration), there were no deaths.
      CONCLUSIONS: The safety of overlapping and nonoverlapping surgical procedures did
      not differ at this children's center. These findings may not extrapolate to other
      centers. LOS or intraoperative measures may be more appropriate than mortality
      for safety evaluations due to low event rates for mortality.

PMID- 29373367
TI  - A Framework for a Battlefield Trauma System for Civilians.

PMID- 29373368
TI  - Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During
      Extracorporeal Cardiopulmonary Resuscitation.
AB  - OBJECTIVE: We tested the hypothesis that systemic administration of an A2AR
      agonist will reduce multiorgan IRI in a porcine model of ECPR. SUMMARY BACKGROUND
      DATA: Advances in ECPR have decreased mortality after cardiac arrest; however,
      subsequent IRI contributes to late multisystem organ failure. Attenuation of IRI
      has been reported with the use of an A2AR agonist. METHODS: Adult swine underwent
      20 minutes of circulatory arrest, induced by ventricular fibrillation, followed
      by 6 hours of reperfusion with ECPR. Animals were randomized to vehicle control,
      low-dose A2AR agonist, or high-dose A2AR agonist. A perfusion specialist using a
      goal-directed resuscitation protocol managed all the animals during the
      reperfusion period. Hourly blood, urine, and tissue samples were collected.
      Biochemical and microarray analyses were performed to identify differential
      inflammatory markers and gene expression between groups. RESULTS: Both the
      treatment groups demonstrated significantly higher percent reduction from peak
      lactate after reperfusion compared with vehicle controls. Control animals
      required significantly more fluid, epinephrine, and higher final pump flow while
      having lower urine output than both the treatment groups. The treatment groups
      had lower urine NGAL, an early marker of kidney injury (P = 0.01), lower plasma
      aspartate aminotransferase, and reduced rate of troponin rise (P = 0.01). Pro
      inflammatory cytokines were lower while anti-inflammatory cytokines were
      significantly higher in the treatment groups. CONCLUSIONS: Using a novel and
      clinically relevant porcine model of circulatory arrest and ECPR, we demonstrated
      that a selective A2AR agonist significantly attenuated systemic IRI and warrants
      clinical investigation.

PMID- 29373370
TI  - Conversion During Laparoscopic Liver Resections: A Step Forward.

PMID- 29373369
TI  - A Nationwide, Systematic, and Comprehensive Assessment of Surgical Capacity in
      Lebanon: Results of the Surgical Capacity in Areas With Refugees (SCAR) Study.
AB  - OBJECTIVE: We sought to perform a systematic, comprehensive, and nationwide cross
      sectional analysis of surgical capacity in Lebanon. BACKGROUND: Providing
      surgical care in refugee areas is increasingly recognized as a global health
      priority. The surgical capacity of Lebanon where at least 1 in 6 inhabitants is
      currently a refugee remains unknown. METHODS: The Surgical Capacity in Areas with
      Refugees cross-sectional study included 3 steps: (1) geographically mapping all
      hospitals providing surgical care in Lebanon, (2) systematically assessing each
      hospital's surgical capacity, and (3) identifying surgical care gaps/disparities.
      First, a list of hospitals in Lebanon and their locations was generated combining
      data from the Lebanese Ministry of Health and Syndicate of Hospitals. Specialty,
      rehabilitation, and maternity facilities were excluded. Second, the validated 5
      domain Personnel, Infrastructure, Procedures, Equipment, and Supplies (PIPES)
      tool was administered in each hospital through a face-to-face or phone interview.
      Hospitals' PIPES indices were computed; data were aggregated and analyzed for
      geographic and private/public disparities. RESULTS: A total of 129 hospitals were
      geographically mapped; 20% were public. The PIPES tool was administered in all
      hospitals (100%). The mean PIPES index was 10.98 (Personnel = 14.91,
      Infrastructure = 15.36, Procedures = 37.47, Equipment = 21.63, Supplies = 24.78).
      The number of hospital beds, operating rooms, surgeons, and anesthesiologists per
      100,000 people were 217, 8, 16, and 9, respectively. Deficiencies in
      infrastructure were significant, whereby 62%, 36%, 16%, and 5% of hospitals lack
      incinerators, pretested blood, intensive care units, and computed tomography,
      respectively. Continuous external electricity was lacking in 16 hospitals (12%).
      Compared to private hospitals, public hospitals had a lower PIPES index (10.48 vs
      11.1, P = 0.022), including lower Personnel and Infrastructure scores (12.31 vs
      15.57, P = 0.03; 14.04 vs 15.7, P = 0.003, respectively). Geographically, the
      administrative governorates with highest refugee concentrations had the lowest
      PIPES indices. CONCLUSIONS: Evaluating surgical capacity in Lebanon reveals
      significant deficiencies, most pronounced in public hospitals in which refugee
      care is provided and in areas with the highest refugee concentration.

PMID- 29373371
TI  - Effect of Polydeoxyribonucleotide Injection in a Patient With Carpal Tunnel
      Syndrome.
AB  - Ultrasound-guided corticosteroid injection into the carpal tunnel is widely
      performed for the management of carpal tunnel syndrome. However, this injection
      may worsen the condition in patients with type 2 diabetes mellitus.
      Polydeoxyribonucleotide was recently recognized as a substitute for
      corticosteroid because of its anti-inflammatory effects. A 41-yr-old woman with
      type 2 diabetes mellitus was admitted to our rehabilitation clinic with a 1-mo
      history of numbness and tingling in her right hand and first three fingers tips.
      She declined corticosteroid treatment because of a previous episode of
      uncontrolled blood glucose levels after corticosteroid injection. Therefore,
      ultrasound-guided polydeoxyribonucleotide injections into the carpal tunnel were
      carried out. At the 6-mo follow-up, the patient demonstrated an improvement in
      the carpal tunnel syndrome symptoms without any complications. Thus,
      polydeoxyribonucleotide injections into the carpal tunnel can be an alternative
      to corticosteroid injections for carpal tunnel syndrome if there are limitations
      because of adverse effects of the latter.

PMID- 29373372
TI  - Ultrasound-Guided Shoulder Injection or Ultrasound Guides the Shoulder
      Injection?: Standard Versus State-of-the-Art.

PMID- 29373373
TI  - Response to the Letter to the Editor on "Point-of-Care Ultrasonography Findings
      and Care Use Among Patients Undergoing Ultrasound-Guided Shoulder Injections".

PMID- 29373374
TI  - An Innovative End-of-Life Nursing Education Consortium Curriculum That Prepares
      Nursing Students to Provide Primary Palliative Care.
AB  - Research has demonstrated that patients facing serious, life-limiting illnesses
      and their families benefit from receiving palliative care. Increasingly, however,
      specialty palliative care has limited resources. Prelicensure nursing students
      who are educated to provide primary palliative care to patients with serious
      illness and at the end of life can fill that gap. This article describes the
      development and implementation of an innovative online nursing curriculum that
      prepares students with essential primary palliative nursing knowledge and skills.

PMID- 29373375
TI  - Use of Team-Based Learning in a Nursing Leadership Course: An Action Research
      Study.
AB  - Team-based learning (TBL) is a learner-centered method widely used in health
      sciences education. The aim of this action research study was to determine the
      contribution of TBL to the learning experience of students participating in a
      nursing leadership course. The study was conducted in 2 cycles over 2 semesters,
      and TBL was embedded in regular class hours. Results suggest that TBL made
      positive contributions to student learning.

PMID- 29373376
TI  - Ventricular septal defect and left ventricular outflow tract obstruction after
      transcatheter aortic valve implantation.
AB  - : Ventricular septal defect (VSD) has been reported as a rare complication after
      transcatheter aortic valve implantation (TAVI), presenting with signs of heart
      failure. Furthermore, left ventricular outflow tract obstruction (LVOTO) may
      worsen after TAVI, especially in cases of severe left ventricular hypertrophy and
      small cavity. However, the simultaneous appearance of VSD and LVOT after TAVI has
      not been reported before. We report a case of combined VSD and LVOTO after TAVI.

PMID- 29373377
TI  - State of Evidence-Based Practice in Physician Assistant Education.
AB  - PURPOSE: Evidence-based practice (EBP) involves using the best evidence available
      to guide patient care. The use of EBP improves patient outcomes and the quality
      of care delivered. Studies have investigated how EBP is taught in other health
      professions but not in physician assistant (PA) programs. The purpose of this
      study was to explore how PA programs teach this subject matter. METHODS: After
      permission was obtained, a survey was adapted from a similar study completed in
      medical schools. Requests were emailed to 186 accredited PA programs with
      available contact information. These data were analyzed using descriptive
      statistics. The text responses were reviewed and summarized to describe how EBP
      was taught in the programs surveyed. RESULTS: Eighty-four responses were received
      from the 186 PA programs contacted with the survey request, giving a 45.2%
      return. Approximately 95% of respondents reported having formal EBP training in
      their curriculum. Respondents reported formal EBP training through a variety of
      educational activities, with time spent on these activities ranging from 4 hours
      to 550 hours. Barriers to implementation of an EBP curriculum were reported by
      27% of respondents, with the most common barrier being lack of time. CONCLUSIONS:
      Most PA programs that responded have formal EBP training in the curriculum. There
      is little standardization regarding the methods used and time spent in these
      activities. The Accreditation Review Commission on Education for the Physician
      Assistant may be able to assist in overcoming the reported barriers and improving
      standardization by implementing a specific EBP accreditation standard.

PMID- 29373378
TI  - Patient Reported Pain After Successful Nonunion Surgery: Can We Completely
      Eliminate It?
AB  - OBJECTIVES: To investigate what factors are associated with continued long-term
      pain after fracture nonunion surgery. DESIGN: Prospective cohort study. SETTING:
      Single Academic Institution. PATIENTS/PARTICIPANTS: Three hundred forty-one
      patients surgically treated for fracture nonunion were prospectively followed.
      Demographics, radiographic evaluations, VAS pain scores, and short
      musculoskeletal functional assessment (SMFA) scores were collected at routine
      intervals. Only patients who had a minimum of 1-year follow-up and complete
      healing were included this analysis. Patients were divided into a high-pain and
      low-pain cohort for comparison. Inclusion criteria for the high-pain cohort were
      defined as any patient who reported a pain score greater than one standard
      deviation above the mean. MAIN OUTCOME MEASURES: Long-term VAS pain scores and
      factors contributing to increased patient-reported long-term VAS pain scores.
      RESULTS: Two hundred seventy patients met criteria and were included in this
      analysis, with 223 patients (82.6%) in the low-pain cohort and 47 patients
      (17.4%) in the high-pain cohort. The mean long-term pain score was 7.47 +/- 1.2
      in the high-pain group and 1.78 +/- 1.9 in the low-pain group. Within the high
      pain cohort, 55.6% of patients reported a net increase in pain from baseline to
      long-term follow-up compared with 10.5% in the low-pain cohort (P < 0.0005). High
      baseline pain score (P = 0.003), increased Charlson comorbidity index (CCI) (P =
      0.008), lower income level (P = 0.014), and current smoking status (P = 0.033)
      were found to be significantly more prevalent in the high-pain cohort.
      CONCLUSIONS: Patients with higher baseline pain scores, elevated Charlson
      comorbidity index, lower income level or history of smoking are at an increased
      risk of reporting significant and potentially debilitating long-term pain after
      nonunion surgery. Although patients may expect complete relieve of pain,
      orthopaedic surgeons must inform patients of the possibility of experiencing pain
      1 year or more postoperatively. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29373379
TI  - Clinically Relevant Outcome Measures Following Limb Osseointegration; Systematic
      Review of the Literature.
AB  - OBJECTIVES: The current standard of care for an amputee is a socket-based
      prostheses. An osseointegrated implant (OI) is an alternative for prosthetic
      attachment. Osseointegration addresses reported problems related to wearing a
      socket interface, such as skin issues, discomfort, diminished function, quality
      of life, prosthetic use, and abandonment. The purpose of this report is to
      systematically review current literature regarding OI to identify and categorize
      the reported clinically relevant outcome measures, rate the quality of available
      evidence, and synthesize the findings. DATA SOURCES: A multidisciplinary team
      used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
      methods. Search methodology was based on identifying clinically relevant
      articles. Three databases were searched: PubMed, CINAHL, and Web of Science.
      STUDY SELECTION: Clinical studies with aggregated data reporting at least 1
      clinically relevant outcome measure were included. DATA EXTRACTION: The Grading
      of Recommendations Assessment, Development, and Evaluation (GRADE) criterion was
      used for critical appraisal and recommendations. CONCLUSIONS: This review
      identified 21 clinically relevant observational studies. Outcome measures were
      categorized into the following 9 categories: vibratory stimulation,
      complications, biomechanics, economics, patient-reported outcome measures,
      electromyography, x-ray, physical functional performance, and energy consumption.
      This systematic review consisted of Level III and IV observational studies.
      Homogeneous outcome measures with strong psychometric properties across
      prospective studies do not exist to date. Higher-level, prospective, randomized,
      long-term, clinically relevant trials are needed to prove efficacy of OI compared
      with socket prosthetic attachment. Osseointegration was at least equivalent to
      sockets in most studies. In some cases, it was superior. Osseointegration
      represents a promising alternative to socket prosthetic attachments for extremity
      amputees. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 29373380
TI  - Cephalomedullary Nail Fixation of Intertrochanteric Femur Fractures: Are Two
      Proximal Screws Better Than One?: Erratum.

PMID- 29373381
TI  - Outpatient management of community-acquired pneumonia.
AB  - PURPOSE OF REVIEW: The first guidelines on community-acquired pneumonia (CAP)
      were published in 1993, but since then many of the challenges regarding the
      outpatient management of CAP persist. These include the difficulty in
      establishing the initial clinical diagnosis, its risk stratification, which will
      dictate the place of treatment, the empirical choice of antibiotics, the relative
      scarcity of novel antibiotics and the importance of knowing local microbiological
      susceptibility patterns. RECENT FINDINGS: New molecular biology methods have
      changed the etiologic perspective of CAP, especially the contribution of virus.
      Lung ultrasound and biomarkers might aid diagnosis and severity stratification in
      the outpatient setting. Antibiotic resistance is a growing problem that
      reinforces the importance of novel antibiotics. And finally, prevention and the
      use of anti-pneumococcal vaccine are instrumental in reducing the burden of
      disease. SUMMARY: Most of CAP cases are managed in the community; however, most
      research comes from hospitalized severe patients. New and awaited advances might
      contribute to aid diagnosis, cause and assessment of patients with CAP in the
      community. This knowledge might prove decisive in the execution of stewardship
      programmes that maintain current antibiotics, safeguard future ones and reinforce
      prevention.

PMID- 29373382
TI  - Cost-Utility Analysis of Virtual and Mannequin-Based Simulation.
AB  - INTRODUCTION: The purposes of this study were to (1) compare learning outcomes
      between students who participated in mannequin-based simulation activities and
      students who participated in virtual simulation activities and (2) describe a
      cost-utility analysis comparing the two types of simulation activities in terms
      of costs and multiple measures of effectiveness. METHODS: Nursing student
      participants were randomly assigned to one of two experimental groups to complete
      either a mannequin-based or virtual simulation activity. The simulation scenario
      was the same for both groups and involved the care of a hospitalized patient
      experiencing a chronic obstructive pulmonary disease exacerbation. Participants
      completed presimulation and postsimulation assessments reflecting qualitative and
      quantitative measures of learning. A random sample of participants from each
      group completed a postsimulation performance assessment during which they
      interacted one on one with a standardized patient. RESULTS: Eighty-four nursing
      students were enrolled in the study and completed the simulation activities.
      There were no significant differences in quantitative measures of learning or
      performance between participants in the mannequin-based and virtual simulation
      groups. Participants' qualitative responses to postintervention written
      reflections and questions yielded additional data for describing learning from
      the two interventions. In the cost-utility analysis, the virtual simulation
      activity had a more favorable cost-utility ratio of US $1.08 versus the mannequin
      based simulation activity's US $3.62. CONCLUSIONS: Healthcare educators striving
      to make evidence-based decisions about how to best employ simulation pedagogy may
      consider these findings about the cost utility of various simulation modalities.
      However, additional research is needed.

PMID- 29373383
TI  - Validity of Simulation-Based Assessment for Accreditation Council for Graduate
      Medical Education Milestone Achievement.
AB  - INTRODUCTION: The Accreditation Council for Graduate Medical Education requires
      biannual evaluation of anesthesiology residents on 25 subcompetency milestones.
      Some milestone domains are particularly challenging to repeatedly and reliably
      observe during clinical care. Simulation-Based Milestones Assessment (SBMA) may
      help overcome these challenges. However, few studies have examined the external
      validation of simulation assessment scores (ie, the relationships between
      simulation-based assessment scores and other standard measures of ability) for
      milestones. This study analyzed whether SBMA scores (1) discriminate by
      postgraduate year, (2) improve over time, and (3) correlate with traditional
      measures of performance. METHODS: This is a retrospective analysis of 55
      residents' SBMA data from 30 scenarios for two academic years. Each scenario was
      evaluated for time-in-training discrimination. Scenarios were then analyzed for
      SBMA scoring trends over time, and SBMA scores were compared with residents'
      clinical evaluations. RESULTS: Twenty-four SBMA scenarios discriminated by
      postgraduate year. Repeated measure analysis of variance showed statistically
      significant between-session score improvements (F (3, 54) = 17.79, P < 0.001).
      Pearson correlation coefficients demonstrated moderate to strong correlation
      between SBMA and clinical evaluations: January 2015 r = 0.67, P < 0.01 (n = 27);
      May 2015 r = 0.43, P = 0.09 (n = 17); November 2015 r = 0.70, P < 0.01 (n = 24);
      and April 2016 r = 70, P < 0.01 (n = 27). CONCLUSIONS: The associations between
      SBMA scores and experience level, time-in-training, and clinical performance
      evaluations provide evidence that SBMA may be used as metrics of residents'
      Accreditation Council for Graduate Medical Education milestone competencies.

PMID- 29373384
TI  - Learning Theory Foundations of Simulation-Based Mastery Learning.
AB  - STATEMENT: Simulation-based mastery learning (SBML), like all education
      interventions, has learning theory foundations. Recognition and comprehension of
      SBML learning theory foundations are essential for thoughtful education program
      development, research, and scholarship. We begin with a description of SBML
      followed by a section on the importance of learning theory foundations to shape
      and direct SBML education and research. We then discuss three principal learning
      theory conceptual frameworks that are associated with SBML-behavioral,
      constructivist, social cognitive-and their contributions to SBML thought and
      practice. We then discuss how the three learning theory frameworks converge in
      the course of planning, conducting, and evaluating SBML education programs in the
      health professions. Convergence of these learning theory frameworks is
      illustrated by a description of an SBML education and research program in
      advanced cardiac life support. We conclude with a brief coda.

PMID- 29373385
TI  - Leveraging Quick Response Code Technology to Facilitate Simulation-Based
      Leaderboard Competition.
AB  - INTRODUCTION: Leaderboards provide feedback on relative performance and a
      competitive atmosphere for both self-guided improvement and social comparison.
      Because simulation can provide substantial quantitative participant feedback,
      leaderboards can be used, not only locally but also in a multidepartment,
      multicenter fashion. Quick Response (QR) codes can be integrated to allow
      participants to access and upload data. We present the development,
      implementation, and initial evaluation of an online leaderboard employing
      principles of gamification using points, badges, and leaderboards designed to
      enhance competition among healthcare providers. METHOD: This article details the
      fundamentals behind the development and implementation of a user-friendly,
      online, multinational leaderboard that employs principles of gamification to
      enhance competition and integrates a QR code system to promote both self
      reporting of performance data and data integrity. An open-ended survey was
      administered to capture perceptions of leaderboard implementation. RESULTS:
      Conceptual step-by-step instructions detailing how to apply the QR code system to
      any leaderboard using simulated or real performance metrics are outlined using an
      illustrative example of a leaderboard that employed simulated cardiopulmonary
      resuscitation performance scores to compare participants across 17 hospitals in 4
      countries for 16 months. The following three major descriptive categories that
      captured perceptions of leaderboard implementation emerged from initial
      evaluation data from 10 sites: (1) competition, (2) longevity, and (3) perceived
      deficits. CONCLUSIONS: A well-designed leaderboard should be user-friendly and
      encompass best practices in gamification principles while collecting and storing
      data for research analyses. Easy storage and export of data allow for
      longitudinal record keeping that can be leveraged both to track compliance and to
      enable social competition.

PMID- 29373386
TI  - High-Fidelity Realistic Acute Medical Simulation and SBAR Training at a Tertiary
      Hospital in Blantyre, Malawi.

PMID- 29373387
TI  - Bibliometric Study of Scientific Research on Scleral Lenses.
AB  - PURPOSE: To analyze the state of scientific publications in the field of scleral
      lenses applying a bibliometric study. METHODS: The database used in this
      bibliometric study was SCOPUS, the largest abstract and citation database of peer
      reviewed literature: scientific journals, books, and conference proceedings.
      Using remote download techniques, articles published between 1962 (year of first
      registrations) and 2015 were selected by entering the main descriptors: "scleral
      contact lenses" and "scleral lenses," limiting the field for the article,
      keywords, and abstract, linked with the OR tab. We applied the following
      bibliometric indicators: Price index, doubling time and annual growth rate, Price
      transience index, Lotka law of scientific productivity, and Bradford zones.
      RESULTS: The authors recovered 361 contributions (articles, reviews, letters to
      the editor, etc.) for 1962 to 2016. The distribution for five-year periods shows
      a significant increase in 2012 to 2016, with a growth of 222.22% in comparison
      with the previous period 2012 to 2016. The countries with the highest production
      are the United states with 135 contributions, United Kingdom with 46, and India
      with 19. The most productive institutions are Harvard Medical school, Boston
      Foundation for Sight, and Moorfields Eye Hospital National Health Service
      Foundation Trust. Classification of authors based on productivity is strongly
      concentrated in small producers, with a transient index of 59.03. The total
      number of authors is 891, representing a coauthor index of 2.47 for the 361
      documents retrieved. The authors with the highest productivity are Kenneth W.
      Pullum, Perry Rosenthal, and Deborah S. Jacobs, with an h-index between 12 and 19
      documents. The number of documents published on scleral lenses shows a
      significant increase in the last 5 years, and currently, they represent only
      1.44% of all publications on contact lenses. CONCLUSIONS: Bibliometric studies
      have become essential tools for evaluating scientific activity, allowing an
      overview of the growth, size, and distribution of scientific literature
      associated with a particular discipline.

PMID- 29373388
TI  - Effect of the Rigid Gas-Permeable Contact Lens Use on the Endothelial Cells in
      Patients With Keratoconus.
AB  - OBJECTIVES: To compare the changes in the corneal endothelial cells of both the
      patients with keratoconus who use rigid gas-permeable (RGP) contact lens and who
      do not use any contact lens with healthy population. METHODS: Thirty-three
      patients with keratoconus who use RGP contact lenses (group 1), 20 patients with
      keratoconus who do not use any contact lens (group 2), and 40 healthy controls
      were included in the study. Changes in the corneal endothelial cells of all
      patients were evaluated using a noncontact specular microscope. Endothelial cell
      density (ECD), coefficient of variability (CV), hexagonal cell percentage (%HEX),
      and central corneal thickness (CCT) of the patients were evaluated in the study.
      RESULTS: In the groups 1, 2, and 3, the mean ECD was 2,420.8+/-247, 2,579.5+/
      240, and 2,589.5+/-271 cells/mm, the mean CV was 357+/-9, 34+/-7, and 34+/-6, the
      mean %HEX was 54.3+/-13, 59.1+/-14, and 57.4+/-10, and the mean CCT was 508+/-33,
      504+/-43, and 561+/-34 MUm, respectively. There was no significant difference
      between the groups in terms of ECD, CV, and %HEX. Although significant
      differences between the groups 1 to 3 and groups 2 to 3 in terms of CCT were
      detected (P=0.001 and P=0.004, respectively), no significant difference was
      observed between the groups 1 and 2. CONCLUSIONS: Although significant difference
      was found between the groups 1 to 2 and normal population in terms of CCT, no
      difference was detected between all the groups in terms of the other parameters.
      In this study, we report that long-term use of RGP contact lens in patients with
      keratoconus had no effect on the corneal endothelial cells.

PMID- 29373389
TI  - Review of Contact Lens-Related Complications.
AB  - The purpose of this article is to provide a review of existing literature
      describing complications with contemporary contact lenses and their management.
      It is envisioned that this will serve as a useful summary of noninfectious and
      infectious complications associated with contact lens wear.

PMID- 29373390
TI  - Optimized Protocol for Testing Multipurpose Contact Lens Solution Efficacy
      Against Acanthamoeba.
AB  - OBJECTIVES: To evaluate the interlaboratory and intralaboratory reproducibility
      of a proposed protocol for multipurpose contact lens solution (MPS) disinfection
      efficacy against Acanthamoeba. METHODS: Acanthamoeba castellanii and Acanthamoeba
      polyphaga and four MPS with different biocidal agents were used to evaluate the
      protocol in two different laboratories. In addition to the negative control, a
      positive control and neutralization control were used. One experiment was
      performed in triplicate, and all other experiments were performed in duplicate in
      each laboratory. Acanthamoeba trophozoites were grown axenically, and cysts were
      generated using the starvation method. Trophozoites and cysts at a concentration
      of 2.0 * 10 to 2.0 * 10 organisms per milliliter were exposed to the test MPS for
      0, 4 or 6 (manufacturer's recommended soak time [MRST]), 8, and 24 hr. Survivors
      were determined by a limiting dilution method that used a most probable number
      evaluation. RESULTS: The positive and negative controls displayed consistent
      results and trends both within each laboratory and between each laboratory for
      trophozoites and cysts of both A. castellanii and A. polyphaga. The
      neutralization control consistently demonstrated the ability of the neutralizing
      agents to neutralize the MPS and the positive control and demonstrated no
      inhibition of Acanthamoeba by the negative control. Testing in triplicate and
      duplicate demonstrated the reproducibility of the protocol both within each
      laboratory and between the laboratories. Our results demonstrated that the MPS at
      the MRST and at 8 hr (likely overnight soak time) are generally more effective
      against trophozoites than they are against cysts. Only the MPS with hydrogen
      peroxide as the biocidal agent was able to provide a greater than three-log kill
      of cysts at the MRST and longer. Among the MPS we tested, trophozoites of A.
      castellanii and A. polyphaga showed similar responses. Some variability was
      observed when testing cysts of both species. In both laboratories, one
      nonhydrogen peroxide containing MPS had some effect (>1 log kill) on A. polyphaga
      cysts. This solution had no effect (<1 log kill) on A. castellanii cysts, A.
      castellanii trophozoites, and A. polyphaga trophozoites. CONCLUSIONS: The
      protocol that we have revised and evaluated is a well-controlled and reproducible
      procedure that can effectively evaluate the efficacy of MPS against Acanthamoeba
      trophozoites. Some variability was observed when testing the cyst stage.

PMID- 29373391
TI  - Integrated HIV-Care Into Primary Health Care Clinics and the Influence on
      Diabetes and Hypertension Care: An Interrupted Time Series Analysis in Free
      State, South Africa Over 4 Years.
AB  - BACKGROUND: Noncommunicable diseases (NCDs), specifically diabetes and
      hypertension, are rising in high HIV-burdened countries such as South Africa. How
      integrated HIV care into primary health care (PHC) influences NCD care is
      unknown. We aimed to understand whether differences existed in NCD care (pre-
      versus post-integration) and how changes may relate to HIV patient numbers.
      SETTING: Public sector PHC clinics in Free State, South Africa. METHODS: Using a
      quasiexperimental design, we analyzed monthly administrative data on 4 indicators
      for diabetes and hypertension (clinic and population levels) during 4 years as
      HIV integration was implemented in PHC. Data represented 131 PHC clinics with a
      catchment population of 1.5 million. We used interrupted time series analysis at
      +/-18 and +/-30 months from HIV integration in each clinic to identify changes in
      trends postintegration compared with those in preintegration. We used linear
      mixed-effect models to study relationships between HIV and NCD indicators.
      RESULTS: Patients receiving antiretroviral therapy in the 131 PHC clinics studied
      increased from 1614 (April 2009) to 57, 958 (April 2013). Trends in new diabetes
      patients on treatment remained unchanged. However, population-level new
      hypertensives on treatment decreased at +/-30 months from integration by 6/100,
      000 (SE = 3, P < 0.02) and was associated with the number of new patients with
      HIV on treatment at the clinics. CONCLUSIONS: Our findings suggest that during
      the implementation of integrated HIV care into PHC clinics, care for hypertensive
      patients could be compromised. Further research is needed to understand
      determinants of NCD care in South Africa and other high HIV-burdened settings to
      ensure patient-centered PHC.

PMID- 29373392
TI  - Randomized Controlled Trial of the SystemCHANGE Intervention on Behaviors Related
      to Cardiovascular Risk in HIV+ Adults.
AB  - OBJECTIVE: To examine the effect of a lifestyle behavior intervention
      (SystemCHANGE) on physical activity and diet quality among sedentary people
      living with HIV (PLHIV). All participants expressed a desire to improve lifestyle
      health behaviors. METHODS: One hundred and seven HIV+ adults were randomized to
      either the intervention (6, in-person, standardized group sessions focusing on
      improving lifestyle behaviors) or a control condition (general advice on AHA diet
      and exercise guidelines). All participants wore an ActiGraph accelerometer and
      completed 24-hour dietary recalls at baseline, 3, and 6 months. Generalized
      estimating equations were used to examine intervention effects. The primary
      activity outcome was time spent in moderate-to-vigorous physical activity, and
      the primary dietary outcome was Healthy Eating Index. RESULTS: Mean age was 53
      years, 65% were male, and 86% African American. Approximately 90% attended at
      least half of the sessions and 60% attended 5 or more sessions. The intervention
      did not significantly improve our primary lifestyle behavior endpoints (P >=
      0.05); however, intervention participants consumed fewer carbohydrates-primarily
      sugar-sweetened beverages-per day and lost 0.732 kg body weight compared with a
      0.153 weight gain in the control group (P = 0.03). CONCLUSIONS: Among sedentary
      PLHIV at high risk of cardiovascular disease, the SystemCHANGE intervention
      reduced daily carbohydrate intake and body weight, but did not increase physical
      activity or improve overall diet quality. Future work should identify fundamental
      personal, interpersonal, and contextual factors that will increase physical
      activity and improve overall diet quality among this population, and integrate
      these factors into tailored, lifestyle interventions for aging PLHIV.

PMID- 29373393
TI  - Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons
      Living With HIV With Opioid Use Disorders Transitioning to the Community: Results
      of a Double-Blind, Placebo-Controlled Randomized Trial.
AB  - OBJECTIVE: To determine whether extended-release naltrexone (XR-NTX) would
      improve or maintain viral suppression (VS) among prisoners or jail detainees with
      HIV and opioid use disorder (OUD) transitioning to the community. DESIGN: A 4
      site, prospective randomized double-blind, placebo-controlled trial was conducted
      among prison and jail inmates with HIV and OUD transitioning to the community
      from September 2010 through March 2016. METHODS: Eligible participants (N = 93)
      were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 66) or placebo
      (n = 27) starting at release and observed for 6 months. The primary outcome was
      the proportion that maintained or improved VS (<50 copies/mL) from baseline to 6
      months. RESULTS: Participants allocated to XR-NTX significantly improved to VS
      (<50 copies/mL) from baseline (37.9%) to 6 months (60.6%) (P = 0.002), whereas
      the placebo group did not (55.6% at baseline to 40.7% at 6 months P = 0.294).
      There was, however, no statistical significant difference in VS levels at 6
      months between XR-NTX (60.6%) vs. placebo (40.7%) (P = 0.087). After controlling
      for other factors, only allocation to XR-NTX (adjusted odds ratio = 2.90; 95%
      confidence interval = 1.04 to 8.14, P = 0.043) was associated with the primary
      outcome. Trajectories in VS from baseline to 6 months differed significantly (P =
      0.017) between treatment groups, and the differences in the discordant values
      were significantly different as well (P = 0.041): the XR-NTX group was more
      likely than the placebo group to improve VS (30.3% vs. 18.5%), maintain VS (30.3%
      vs. 27.3), and less likely to lose VS (7.6% vs. 33.3%) by 6 months. CONCLUSIONS:
      XR-NTX improves or maintains VS after release to the community for incarcerated
      people living with HIV with OUD.

PMID- 29373394
TI  - Associations Between Multiple Forms of Discrimination and Tobacco Use Among
      People Living With HIV: The Mediating Role of Avoidance Coping.
AB  - BACKGROUND: People living with HIV (PLWH) have higher levels of tobacco use
      compared with the general population, increasing their risk of morbidity and
      mortality. PLWH also face potential chronic stressors related to the stigma and
      discrimination associated with HIV and other characteristics (eg, race and sexual
      orientation). These experiences may be associated with harmful health behaviors,
      such as tobacco use. The purpose of the current study is to explore the
      psychosocial context of tobacco use in PLWH, examining avoidance coping as a
      mediator in the relationship between multiple forms of discrimination and tobacco
      use. SETTING: Participants included 202 PLWH recruited from an HIV primary care
      clinic in Birmingham, AL, between 2013 and 2015. METHODS: Participants responded
      to parallel items assessing experiences of discrimination related to HIV status,
      race, and sexual orientation, as well as items assessing avoidance coping. Data
      on current tobacco use were obtained from participants' clinic records. Mediation
      models for each form of discrimination (HIV, race and sexual orientation)
      adjusting for demographic variables and the other forms of discrimination were
      evaluated. RESULTS: The indirect effect of HIV-related discrimination on
      likelihood of tobacco use through avoidance coping was significant, suggesting
      that avoidance coping mediates the association between HIV-related discrimination
      and tobacco use. However, the indirect effects of the other forms of
      discrimination were not significant. CONCLUSIONS: Given the disparity in tobacco
      use in PLWH, behavioral scientists and interventionists should consider including
      content specific to coping with experiences of discrimination in tobacco
      prevention and cessation programs for PLWH.

PMID- 29373395
TI  - Repetitive Deep TMS for Parkinson Disease: A 3-Month Double-Blind, Randomized
      Sham-Controlled Study.
AB  - PURPOSE: To study the effects of a repetitive deep transcranial magnetic
      stimulation (rDTMS) in patients with Parkinson disease using the H5 coil for the
      low-frequency stimulation of the primary motor cortex, followed by the high
      frequency rDTMS of the prefrontal cortex. METHODS: The main outcome measures were
      the total and motor scores of the Unified Parkinson's Disease Rating Scale
      (UPDRS). Secondary measures included rating of depression and quantitative motor
      tasks. RESULTS: Forty-eight patients were randomized 1:1 into real or sham rDTMS
      treatment arms. Analyses (n = 42) of both UPDRS scores revealed a significant
      main effect for time between baseline and day 90 (end of treatment), indicating
      that there was an improvement of both scores over time in the whole sample.
      Although effects of treatment and time-by-treatment were insignificant, simple
      effects analysis of both measures was significant in the rDTMS group and reached
      a P-value of 0.06 in the sham group. The response rate was higher in patients
      with longer disease duration and higher motor UPDRS scores. Side effects were
      more common in the rDTMS group but were transient and tolerable. CONCLUSIONS:
      Although rDTMS treatment exhibited some motor improvements, we could not
      demonstrate an advantage for real treatment over sham. Further research is
      required to establish stimulation parameters that may induce potentially more
      beneficial outcomes, probably in patients with longer and more sever disease.

PMID- 29373396
TI  - Clinical Neurophysiology Training in a Developing Country: Institutional
      Resources and Profiles.
AB  - PURPOSE: The purpose of this study was to describe the characteristics and
      preferences of clinical neurophysiology (CN) fellows, as well as the resources
      available for their training, in a developing country such as Mexico. METHODS: An
      online survey (25 questions) was given to Mexican CN fellows from May to June
      2017, covering their reasons for choosing the CN subspecialty, their activities,
      future plans, institutional resources, and administrative staff. Descriptive
      statistics were used. RESULTS: Total respondents: 20/22 (90%), 65% female from 7
      CN centers (80% public and 20% private hospitals) in Mexico City. Seventy-five
      percent chose CN out of personal interest, and all were not unsatisfied with
      their academic program. Most plan to work in private practice (75%) and are
      interested in learning EEG (85%) and intraoperative monitoring (75%-85%). The
      highest-reported training time by CN area allocated by the programs was as
      follows: EEG (27%), electromyography (22%), and evoked potentials (16%). The
      average number of fellows per center was 4; 75% of the centers perform epilepsy
      surgery, of which 60% offer invasive intracranial studies for the evaluation of
      surgical candidates. CONCLUSIONS: Mexican CN fellows are satisfied with their
      choice and with the academic program. They are increasingly interested in
      intraoperative monitoring, which is not addressed in current Mexican CN Programs.

PMID- 29373397
TI  - Getting a Charge Out of You.

PMID- 29373400
TI  - LEGISLATIVE DEPARTMENT.

PMID- 29373398
TI  - PERSPECTIVES.

PMID- 29373402
TI  - PRODUCTS AND INFORMATION.

PMID- 29373403
TI  - Heroes-and You-Can Make a Difference.

PMID- 29373404
TI  - Idiopathic Canalicular Inflammatory Disease: New Disease Description of Clinical
      Patterns, Investigations, Management, and Outcomes.
AB  - PURPOSE: The objective of this perspective is to present a separate disease
      description of "idiopathic canalicular inflammatory disease" and outline the
      diagnostic criteria and early experiences with its investigations and management.
      METHODS: Retrospective case series of 44 canaliculi of 22 eyes of 11 patients
      presenting at a tertiary care Dacryology service over a period of 2 years with
      typical clinical patterns of inflammatory canaliculitis and its outcomes were
      studied. All the patients underwent microbiological work-up with culture and
      sensitivity, dacryoendoscopy imaging, serial Fourier domain ocular coherence
      tomography, and collagen vascular profiles. Stages in the evolution of the
      disease were studied. All patients were treated initially with topical steroids
      followed by punctal dilatation and placement of mini-monoka stents. Five patients
      in addition had a small biopsy from the inflamed portion of the vertical
      canaliculus. Stents were extubated at 6 weeks. RESULTS: Forty-four canaliculi
      were diagnosed to have idiopathic canalicular inflammatory disease during the
      study period. There was a female preponderance (81.8%, 9/11) and the mean age at
      presentation was 57 years. All patients presented with unilateral epiphora
      without any discharge, pain, or swelling. Collagen vascular profiles and
      screening for autoimmune diseases were negative. Clinical picture ranged from
      stages 1 to 5, consisting of edema, progressive centripetal vascularization,
      pouting of vascularized mucosa, membrane formation, and progressive scarring. The
      presentation begins in 1 eye and usually involves the other eye at a mean of 6
      months. Ocular coherence tomography and dacryoendoscopy were of adjunctive value
      in the diagnosis. Histopathological examination was suggestive of a chronic
      inflammation. All patients had relentless progression to end-stage disease,
      although delayed significantly by steroids and monoka intubation. CONCLUSION:
      Idiopathic canalicular inflammatory disease has a distinct and typical clinical
      behavior and the current study proposed diagnostic features and disease staging.
      The use of topical and systemic immunosuppressive agents needs to be explored to
      formulate effective protocols for its management.

PMID- 29373405
TI  - Bony Regrowth After Deep Lateral Orbital Decompression.
AB  - PURPOSE: To report on 2 cases of late bony regrowth with clinically apparent
      proptosis after deep lateral orbital decompression for thyroid orbitopathy.
      METHODS: A retrospective review of 2 cases identified by the authors as having
      late bony regrowth. The authors review the clinical, historical, radiologic, and
      anatomical findings and discuss the significance thereof. RESULTS: Bony regrowth
      with bowing toward the middle cranial fossa is observed at postoperative month 8
      in the first case. Cortical bone and marrow was observed to regrow at 2 years
      postoperatively in the second case. Both patients underwent successful repeat
      deep lateral orbital decompression with resolution of proptosis and clinical
      symptoms. CONCLUSIONS: Late bony regrowth should be considered as a possible
      cause of recurrent proptosis after orbital decompression in thyroid eye disease.

PMID- 29373407
TI  - The Individualized Facelift Technique in Improving Facial Asymmetry for Asian
      Patients.
AB  - PURPOSE: Among multiple influential factors affecting facial symmetry, the role
      of soft tissue is often overlooked. Skin and skeletal differences between Asian
      and Caucasian people also require the adaptation of current techniques for Asian
      patients. This article aimed to explore the ability of individual facelift
      techniques to improve facial symmetry and reset youthful eye in Asian people,
      while a new method, called the grid method, was tried to evaluate the improvement
      in facial symmetry. METHODS: The authors conducted a review of 58 consecutive
      facelifts, which were all performed by a single surgeon between April 2009 and
      December 2016 following institutional review board approval. Among them, 21
      patients underwent lower eyelid blepharoplasty. The original frontal photograph
      of each patient was evaluated by the grid method. Five independent plastic
      surgeons reviewed the facial asymmetry of the images before and after the
      operations using a visual analog scale to analyze the facial asymmetry of the
      patients. RESULTS: In the preoperative group evaluated by the grid, the mean
      facial asymmetry score was 4.11, while in the postoperative group, the mean score
      was 1.07, which was significantly lower than the mean score before the operation
      (p < 0.001). The change in mean scores illustrated that the technique was
      effective in improving facial symmetry in Asian people. A total of 8 patients
      experienced hematomas and recovered well without obvious sequelae. CONCLUSIONS:
      The individual facelift technique was effective for improving facial symmetry and
      reshaping youthful eye in Asian people.

PMID- 29373406
TI  - Interlamellar Autogenous Tarsal Graft for the Correction of Lower Eyelid
      Trichiasis Associated With Eyelid Margin Thinning.
AB  - PURPOSE: To evaluate the use of autogenous tarsal graft for surgical correction
      of lower eyelid trichiasis associated with eyelid thinning. METHODS: A total of
      23 eyelids of 19 consecutive patients with trichiasis were operated with a
      variant of the Van Millingen procedure. The surgery consisted of interposing a 3
      mm high fragment of autogenous ipsilateral upper eyelid tarsus corresponding to
      the trichiasis segment between the pretarsal anterior lamella and the lower
      tarsal plate. Preoperative assessment included quantification of eyelid thickness
      on the midpoint of the segment with trichiasis, biomicroscopy of the eyelid
      margin and location of the trichiasis. All patients were examined at 1, 3, 6, and
      12 months after surgery. Eyelid thickness was measured at 1 month and 12 months
      of follow up. RESULTS: Preoperatively the mean thickness of the eyelid margin was
      0.99 mm +/- 0.06 standard error. One month postoperatively eyelid thickness
      increased to 2.08 +/- 0.28 standard error, decreasing over time to reach 1. 48 mm
      +/- 0.18 standard error 1 year after surgery, a value that did not differ from
      that of the control group. Small granulomas were diagnosed only in the early
      phases of the postoperative period. Trichiasis recurrence was seen in just 1
      eyelid. Isolated abnormal lashes lateral or medial to the graft were present in 5
      eyelids at the end of the study. CONCLUSIONS: Autogenous tarsal grafts placed
      parallel to the lower tarsus are a good option both to correct misdirected
      eyelashes and to restore normal lower eyelid thickness.

PMID- 29373408
TI  - From the Editors.

PMID- 29373409
TI  - Letter to the Editor.

PMID- 29373410
TI  - The Arrest of the University of Utah Nurse Was Wrong!: The Legal and Ethical
      Issues Discussed and Lessons Learned.

PMID- 29373411
TI  - JPNN Best Manuscripts and Reviewers of the Year.

PMID- 29373412
TI  - Transitions in Care: Risk, Recovery, and Best Practices.

PMID- 29373413
TI  - The Art of Skillful Disclosure.

PMID- 29373414
TI  - Emerging Trends in Perinatal Quality and Risk With Recommendations for Patient
      Safety.

PMID- 29373416
TI  - Oxytocin Use in Labor: Legal Implications.

PMID- 29373415
TI  - Ethical Considerations of a Neonatal Intensive Care Unit Pharmacist.

PMID- 29373417
TI  - Marijuana-Perinatal and Legal Issues With Use During Pregnancy.
AB  - Although still illegal at the federal level, marijuana has been legalized for
      medical and/or recreational use in 29 states, causing a dynamically changing
      legal and social landscape. While the legalization of marijuana at the state
      level provides criminal protection for use by adults, there remain civil legal
      implications for families brought about by mandated reporting laws. Mandated
      reporting requirements have not been updated to account for the movement toward
      legalization, risking overload of community child protection resources. There is
      little evidence to inform development of guidelines and protocols for screening,
      educating, testing of mothers and newborns, and reporting. There are perinatal
      issues in this evolving environment as well. Discriminatory testing, length of
      time the drug remains in the system, potential for compromised provider-patient
      relationships, inconsistent education and referrals, breastfeeding during
      marijuana use, punitive or legal interventions that may have a negative
      psychosocial impact on a new family, and the risk for development of community
      standards of care based on opinion rather than science are just a few of the
      issues realized after marijuana legalization. These legal and perinatal issues
      are discussed in detail, along with considerations for practice and policy in
      caring for cannabis-exposed pregnant women and newborns.

PMID- 29373418
TI  - Litigation in Perinatal Care: The Deposition Process.
AB  - Litigation in perinatal nursing represents a disproportionate share of indemnity
      payouts and results in excessive psychological stress. Testimony at deposition or
      trial can be challenging for clinicians; little is taught in training or
      postgraduate education regarding litigation. Nurses, midwives, and physicians can
      effectively navigate the deposition process and prepare for trial testimony by
      understanding the plaintiff's goals, recognizing the role of documentation, and
      becoming familiar with various plaintiff's strategies including reptile theory.
      Knowledge of psychological concepts such as confirmation bias and cognitive
      dissonance may assist clinicians in responding to plaintiff's lines of
      questioning. Deposition preparation is crucial to the defense and requires active
      participation on the part of clinicians; it may include mock deposition or use of
      simulation laboratories. Common mistakes in deposition may be avoided with
      foresight and anticipatory planning by clinicians working closely with risk
      managers and defense attorneys. This article provides an overview of the
      deposition process, including the plaintiff's goals and common approaches, as
      well as the role of documentation and common errors of deponents.

PMID- 29373419
TI  - Institutional Betrayal and Gaslighting: Why Whistle-Blowers Are So Traumatized.
AB  - Despite whistle-blower protection legislation and healthcare codes of conduct,
      retaliation against nurses who report misconduct is common, as are outcomes of
      sadness, anxiety, and a pervasive loss of sense of worth in the whistle-blower.
      Literature in the field of institutional betrayal and intimate partner violence
      describes processes of abuse strikingly similar to those experienced by whistle
      blowers. The literature supports the argument that although whistle-blowers
      suffer reprisals, they are traumatized by the emotional manipulation many
      employers routinely use to discredit and punish employees who report misconduct.
      "Whistle-blower gaslighting" creates a situation where the whistle-blower doubts
      her perceptions, competence, and mental state. These outcomes are accomplished
      when the institution enables reprisals, explains them away, and then pronounces
      that the whistle-blower is irrationally overreacting to normal everyday
      interactions. Over time, these strategies trap the whistle-blower in a maze of
      enforced helplessness. Ways to avoid being a victim of whistle-blower
      gaslighting, and possible sources of support for victims of whistle-blower
      gaslighting are provided.

PMID- 29373420
TI  - Institutional Betrayal and Gaslighting: Why Whistle-Blowers Are So Traumatized.

PMID- 29373421
TI  - Partnering With a Medical Malpractice Insurer to Improve Patient Safety and
      Decrease Risk.
AB  - Implementing evolving science into clinical practice remains challenging.
      Assimilating new scientific evidence into clinical protocols and best practice
      recommendations, in a timely manner, can be difficult. In this article, we
      examine the value of partnering with a captive medical malpractice insurance
      company and its Patient Safety Organization to use data and convening
      opportunities to build upon the principles of implementation science and foster
      efficient and widespread adoption of the most current evidence-based
      interventions. Analyses of medical malpractice and root-cause analysis data set
      the context for this partnership and acted as a catalyst for creating best
      practice guidelines for adopting therapeutic hypothermia in the treatment of
      neonatal encephalopathy. What follows is a powerful example of successfully
      leveraging the collective wisdom of healthcare providers across specialties and
      institutional lines to move patient safety forward while managing risk.

PMID- 29373423
TI  - Care Through the Newborn's Eyes.
AB  - Separation of mothers and infants after birth is standard practice for many
      hospitals, yet not evidence-based. Nonseparation clearly has numerous benefits.
      However, newborns lack a voice to make choices to direct their course of care.
      The evidence supports nonseparation strategies for mothers and infants that
      promote attachment, physiologic regulation, nutrition, sleep, communication, and
      management of stress/pain. Moreover, the evidence is compelling that
      nonseparation is essential. The time has come to act on the evidence and begin
      seeing the care we provide through the newborn's eyes.

PMID- 29373422
TI  - Infants in Drug Withdrawal: A National Description of Nurse Workload, Infant
      Acuity, and Parental Needs.
AB  - Infants in drug withdrawal have complex physiological and behavioral states,
      requiring intensive nursing care. The study objectives were to describe acuity,
      parental needs, and nurse workload of infants in drug withdrawal compared with
      other infants. The design was cross-sectional and involved secondary nurse survey
      data from 6045 staff nurses from a national sample of 104 neonatal intensive care
      units. Nurses reported the care of 15 233 infants, 361 (2.4%) of whom were in
      drug withdrawal. Three-fourths of hospitals had at least 1 infant in drug
      withdrawal. In these hospitals, the mean number of infants in drug withdrawal was
      4.7. Infant acuity was significantly higher among infants in drug withdrawal.
      Parents of infants in drug withdrawal required significantly more care to address
      complex social situations (51% vs 12%). The number of infants assigned to nurses
      with at least 1 infant in withdrawal (mean = 2.69) was significantly higher than
      typical (mean = 2.51). Given infant acuity and parental needs, policies
      legislating patient-to-nurse ratios should permit professional discretion on the
      number of patients to assign nurses caring for infants in drug withdrawal.
      Managers and charge nurses should consider the demands of caring for infants in
      drug withdrawal in assignment decisions and provide support and education.

PMID- 29373424
TI  - Grateful for the Generosity of Strangers.

PMID- 29373425
TI  - The Effect of Heat Stress on Measures of Running Performance and Heart Rate
      Responses During A Competitive Season in Male Soccer Players.
AB  - Measures of running performance (RP) and heart rate responses (HR) to matchplay
      during three different heat stress (HS) conditions were assessed in seven
      National Collegiate Athletic Association (NCAA) Division I male soccer players.
      Total distance (TD), as well as distance covered within distinct velocity zones
      [walking (WALK), jogging (JOG), low speed running (LSR), high-speed running
      (HSR), sprinting (SPRINT), low-intensity running (LIR), and high-intensity
      running (HIR)] were assessed using GPS units over 12 matches. HS was monitored
      during each match, and matches were defined as low (HSlow, n=4), moderate (HSmod,
      n=4), or high (HShigh, n=4) HS. Minutes played were significantly different
      across HS conditions (p=0.03). Therefore, distance covered within each movement
      velocity was assessed relative to minutes played, and as a percentage of total
      playing time. WALKrel was significantly greater during HShigh compared to HSlow
      (p=0.035). LIRrel was significantly greater during HSmod (p=0.015) compared to
      HSlow. A trend was observed for %WALK being higher during HShigh compared to
      HSlow (p=0.066). %LIR was significantly greater during HShigh compared to HSlow
      (p=0.048). HIR was not significantly different across HS conditions. Percent of
      time spent >85% HRmax was significantly greater during HShigh (p=0.002) and HSmod
      (p<0.001) compared to HSlow. Percent of time spent between 65-84% HRmax was
      significantly greater during HSlow compared to HShigh (p<0.001). Results indicate
      that HS resulted in increased LIR and %HR>=85, while HIR was maintained. HIR
      performance may be conserved through decreased playing time and/or the adoption
      of pacing strategies. This may assist coaches in altering player management
      strategies to optimize team performance.

PMID- 29373426
TI  - Tapering Practices of Strongman Athletes.
AB  - Winwood, PW, Dudson, MK, Wilson, D, Mclaren-Harrison, JKH, Redjkins, V,
      Pritchard, HJ, and Keogh, JWL. Tapering practices of strongman athletes. J
      Strength Cond Res 32(5): 1181-1196, 2018-This study provides the first empirical
      evidence of how strongman athletes taper for strongman competitions. Strongman
      athletes (n = 454) (mean +/- SD: 33.2 +/- 8.0 years, 178.1 +/- 10.6 cm, 108.6 +/-
      27.9 kg, 12.6 +/- 8.9 years general resistance training, 5.3 +/- 5.0 years
      strongman implement training) completed a self-reported 4-page internet survey on
      tapering practices. Analysis by sex (male and female), age (<=30 and >30 years),
      body mass (<=105 and >105 kg), and competitive standard (local/regional amateur,
      national amateur and professional) was conducted. Eighty-seven percent (n = 396)
      of strongman athletes reported that they used a taper. Athletes stated that their
      typical taper length was 8.6 +/- 5.0 days, with the step taper the most commonly
      performed taper (52%). Training volume decreased during the taper by 45.5 +/-
      12.9%, and all training ceased 3.9 +/- 1.8 days out from competition. Typically,
      athletes reported that training frequency and training duration stayed the same
      or decreased and training intensity decreased to around 50% in the last week.
      Athletes generally stated that tapering was performed to achieve recovery, rest,
      and peak performance; the deadlift, yoke walk, and stone lifts/work took longer
      to recover from than other lifts; assistance exercises were reduced or removed in
      the taper; massage, foam rolling, nutritional changes, and static stretching were
      strategies used in the taper; and, poor tapering occurred when athletes trained
      too heavy/hard or had too short a taper. These data will assist strongman
      athletes and coaches in the optimization of tapering variables leading to more
      peak performances. Future research could investigate the priming and
      preactivation strategies strongman athletes use on competition day.

PMID- 29373427
TI  - Noninvasive Assessment of Internal and External Player Load: Implications for
      Optimizing Athletic Performance.
AB  - Heishman, AD, Curtis, MA, Saliba, E, Hornett, RJ, Malin, SK, and Weltman, AL.
      Noninvasive assessment of internal and external player load: implications for
      optimizing athletic performance. J Strength Cond Res 32(5): 1280-1287, 2018-Few
      data exist that assess athlete tracking and monitoring for the development of
      strategies to optimize performance and reduce fatigue in elite athletes. The
      purpose of the present study was to assess the efficacy of external load and
      internal stress monitoring as assessment tools for examining a performance index
      of fatigue. A retrospective analysis was performed on data collected over the
      course of the preseason in 10 elite male NCAA Division 1 basketball players.
      Internal stress was assessed using Omegawave Technology readiness scores and
      compared with the performance index of countermovement jump (CMJ). The external
      load that accumulated during the previous practice, quantified by PlayerLoad (PL;
      Catapult), was compared with CMJ values and Omegawave scores. The results
      indicated that high, compared to low CNS Omegawave Readiness Scores (6.7 +/-
      05.1, 4.5 +/- 1.2 AU; p < 0.001), were associated with increased CMJ (62.1 +/-
      6.5 vs. 59.4 +/- 6.6 cm; p = 0.05), Power (6,590 +/- 526.7 vs. 6,383.5 +/- 606.8
      W; p = 0.05), Omegawave Overall Readiness (5.8 +/- 1.1 vs. 5.0 +/- 0.7 AU; p =
      0.05), and Omega Potential (Omega) (21.3 +/- 6.3 vs. 9.9 +/- 20.8 mV; p = 0.07).
      An increased PL during the previous exposure was associated with decreased CMJ
      (58.7 +/- 4.7 cm vs. 60.4 +/- 5.1 cm; p < 0.001) and increased TRIMP (135.1 +/-
      35.9 vs. 65.6 +/- 20.0 AU; p < 0.001), and duration (115.4 +/- 27.1 vs. 65.56 +/-
      20.0 minutes; p = < 0.001) despite no differences in Omegawave CNS Readiness
      scores. We conclude that Omegawave and Catapult technologies provide independent
      information related to performance and may be effective tools for monitoring
      athlete performance.

PMID- 29373428
TI  - Four-Week Unstructured Break Improved Athletic Performance in Collegiate Rugby
      Players.
AB  - Jensen, CD, Gleason, D, and VanNess, JM. Four-week unstructured break improved
      athletic performance in collegiate rugby players. J Strength Cond Res 32(6): 1671
      1677, 2018-This study analyzed the changes in athletic performance and
      anthropometric characteristics in collegiate male club rugby athletes (n = 14)
      after a 4-week winter break. All measurements were collected before and after the
      break. Body composition was assessed by body mass index and hydrostatic weighing.
      Performance measurements were as follows: V[Combining Dot Above]O2max, vertical
      jump, 10-yard sprint, squat max, and bench press max. Before testing, each
      subject was acclimated to the protocols to reduce learning effects. During the 4
      week break, no workouts were provided for the athletes; it was unsupervised and
      unstructured. Participants were required to maintain and submit self-reported
      nutritional and activity logs during this period. After the break, the athletes
      demonstrated a 5.0% improvement in V[Combining Dot Above]O2max (absolute increase
      of 2.25 ml.kg.min), 6.8% improvement in vertical jump (1.50 inches), and a 14.3%
      increase in squat max (38.64 lb). Although increases in body mass (1.0%) were not
      significant, the body fat percentage exhibited a relative increase of 19.3%
      (absolute change from 13.35 to 15.93%). A significant discriminate function
      analysis indicated statistical differences between groups based on these
      variables. Self-reported behavior logs confirmed participation in >3 days of
      moderate to intense physical activity per week but somewhat poor dietary habits.
      These results indicate that collegiate rugby athletes may not need prescribed
      exercise routines during seasonal breaks in the athletic schedule. However, it
      may be beneficial to provide structured nutritional advice during unsupervised
      periods.

PMID- 29373429
TI  - Gender differences in mechanical properties of the Achilles tendon: Longitudinal
      response to repetitive loading exercise.
AB  - Gender differences have been observed in the mechanical properties of the
      Achilles tendon, which may help to explain the increased risk of injury in males.
      However, the response and recovery of tendon mechanics to repetitive loading
      exercise, as well as gender dependent responses, are not well understood. Our
      purpose was to compare Achilles tendon mechanical properties between males and
      females prior to, immediately after, and 60-minutes following a repetitive
      loading exercise. Seventeen female (age: 24.0 +/- 3.9yrs; height: 167.4 +/-
      6.9cm; mass: 64.9 +/- 8.5kg) and 18 male (age: 23.9 +/- 2.4yrs; height: 179.2 +/-
      5.09cm; mass: 78.4 +/- 8.7kg) recreationally active individuals volunteered.
      Utilizing isokinetic dynamometry and diagnostic ultrasound, baseline levels of
      Achilles tendon force, elongation, stiffness, stress, strain and Young's modulus
      were assessed prior to 100 successive calf raises using a Smith machine at 20% of
      participant body mass. Outcomes were reassessed immediately, and 60-minutes post
      exercise. Females exhibited less Achilles tendon force, stiffness, stress and
      modulus compared to males, regardless of time point. Both genders responded to
      repetitive loading exercise similarly, with immediate decreases in mechanical
      properties of the Achilles tendon from baseline to immediately post-exercise.
      Tendon properties were observed to be equal to baseline values at 60-min post
      exercise. Baseline differences in tendon properties may help to explain the
      disparity in injury risk, as both genders responded to and recovered from
      exercise similarly. Future research should aim to include additional time points
      (both leading up to and following 60-minutes), and assess tendon responses to
      more sport specific activities, while also including patients diagnosed with
      Achilles tendon injuries.

PMID- 29373430
TI  - Post Activation Potentiation and Concentric Contraction Performance: Effects on
      Rate of Torque Development, Neuromuscular Efficiency and Tensile Properties.
AB  - This study investigated how a 6s maximal voluntary isometric conditioning
      contration (MVIC) affected plantar flexor twitch rate of torque development
      (RTDTW), as well as peak torque (PTCC) and rate of torque development (RTDCC) of
      maximal voluntary concentric contractions (MVCC) performed at 60 degrees /s.
      RTDCC and normalized triceps surae electromyography signals (EMGTS) were measured
      during different phases of contraction. Additionally, muscle tendon unit passive
      stiffness index (SI) calculated from the torque-angle relation was measured
      following each MVCC.Enhancements were found in the RTDTW immediately (by 59.7%)
      and up to 480s (by 6.0%) post MVIC (p<0.05). RTDCC during the 100-200ms, 50
      200ms, and 0-200ms phases and PTCC were enhanced (by 5.7-9.5%) from 90-300s post
      conditioning (p<0.05). Neuromuscular efficiency increased (decreased EMGTS/RTDCC)
      in the 50-200ms and 0-200ms phases by 8.8-12.4%, from 90-480s post MVIC (p<0.05).
      No significant changes were found in the SI or in RTDCC during the 50-100ms
      phase, suggesting that the enhancements reported, reflect mainly contractile
      rather than neural or tensile mechanisms.PAP effects on PTCC and RTDCC were
      significant, and more durable at a lower velocity than previously reported.
      Enhancement in RTDCC and neuromuscular efficiency were found to be more prominent
      in later phases (>100ms) of the MVCC. This suggests that enhanced contractile
      properties, attained via MVIC, benefit concentric contraction performance.

PMID- 29373431
TI  - The Importance of Strength and Power on Key Performance Indicators in Elite Youth
      Soccer.
AB  - The purpose of this investigation was to examine the importance of strength and
      power in relation to key performance indicators (KPI's) within competitive soccer
      match play. This was achieved through using an experimental approach where
      fifteen subjects were recruited from a professional soccer club's scholarship
      squad during the 2013/14 season. Following anthropometric measures, power and
      strength were assessed across a range of tests which included the squat jump
      (SJ), countermovement jump (CMJ), 20 metre (m) sprint and arrowhead change of
      direction test. A predicted 1-repetition maximum (RM) was also obtained for
      strength by performing a 3RM test for both the back squat and bench press and a
      total score of athleticism (TSA) was provided by summing z-scores for all fitness
      tests together, providing one complete score for athleticism. Performance
      analysis data was collected during 16 matches for the following KPIs: passing,
      shooting, dribbling, tackling and heading. Alongside this, data concerning player
      ball involvements (touches) was recorded. Results showed that there was a
      significant correlation (p < 0.05) between CMJ (r = 0.80), SJ (r = 0.79) and TSA
      (r = 0.64) in relation to heading success. Similarly, a significant correlation
      (p < 0.05) between predicted 1RM squat strength and tackle success (r = 0.61).
      These data supports the notion that strength and power training are important to
      soccer performance, particularly when players are required to win duels of a
      physical nature. There were no other relationships found between the fitness data
      and the KPI's recorded during match play which may indicate that other aspects of
      player's development such as technical skill, cognitive function and sensory
      awareness are more important for soccer-specific performance.

PMID- 29373432
TI  - Comparison of sprint interval and endurance training in team sport athletes.
AB  - PURPOSE: High volume endurance training (ET) has traditionally been used to
      improve aerobic capacity but is extremely time-consuming in contrast to low
      volume short duration sprint interval training (SIT) that improves maximal oxygen
      uptake (V[Combining Dot Above]O2max) to a similar extent. Few studies have
      compared the effects of SIT versus ET using running-based protocols, or in team
      sport athletes. METHODS: Club level male Gaelic football players were randomly
      assigned to SIT (n=7; 21.6 +/- 2.1 yr) or ET (n=8; 21.9 +/- 3.5 yr) for six
      sessions over two weeks. V[Combining Dot Above]O2max, muscle mitochondrial enzyme
      activity, running economy (RE), and high intensity endurance capacity (HEC) were
      measured before and after training. RESULTS: An increase in V[Combining Dot
      Above]O2max (P<0.05) following two weeks of both SIT and ET was observed.
      Performance in HEC increased by 31.0% and 17.2% after SIT and ET, respectively
      (P<0.05). RE assessed at 8, 9, 10 and 11 kmh, lactate threshold and vV[Combining
      Dot Above]O2max were unchanged following both SIT and ET. Maximal activity of 3
      beta-hydroxylacyl coenzyme A dehydrogenase (beta-HAD) was increased in response
      to both SIT and ET (P<0.05), whereas the maximal activity of citrate synthase
      remained unchanged following training (p=0.07). CONCLUSION: A running-based
      protocol of SIT is a time-efficient training method for improving aerobic
      capacity and HEC, and maintaining indices of running economy and lactate
      threshold in team sport athletes.

PMID- 29373433
TI  - Leptin and Leptin Receptor Genes Are Associated With Obesity-Related Traits
      Changes in Response to Aerobic Training Program.
AB  - Leonska-Duniec, A, Jastrzebski, Z, Jazdzewska, A, Krzysztof, F, and Cieszczyk, P.
      Leptin and leptin receptor genes are associated with obesity-related traits
      changes in response to aerobic training program. J Strength Cond Res 32(4): 1036
      1044, 2018-Leptin (LEP) and leptin receptor (LEPR) genes have been studied for
      their potential association with development of human obesity and its related
      complications. Therefore, we have decided to check whether selected body mass,
      body composition, and metabolic variables observed in physically active
      participants will be modulated by the polymorphisms. The genotype distribution
      was examined in a group of 201 women measured for chosen traits before and after
      the completion of a 12-week aerobic training program. Our results revealed a
      significant interaction between training and LEP genotype for glucose level. A
      training-related decrease in plasma glucose concentration in the LEP AG
      heterozygotes differed significantly from the change in the homozygotes. The
      polymorphism was also associated with fat-free mass (FFM), total body water
      (TBW), total cholesterol, triglycerides, and low-density lipoprotein cholesterol
      (LDL-C) levels. Another finding was a significant interaction between training
      and LEPR for LDL-C level. As opposed to AG and GG, AA homozygotes demonstrated a
      training-related decrease in LDL-C level. Our findings also showed that the LEPR
      G allele is connected with obesity-related traits. The participants with the GG
      genotype had higher body mass, body mass index (BMI), FFM, and TBW during the
      entire study period. This study provides evidence that polymorphisms in the LEP
      and LEPR genes are associated with the magnitude of the effects of regular
      physical activity on glucose and LDL-C levels, respectively. In addition, we
      found the association of the G allele of the LEPR polymorphism with body mass and
      BMI.

PMID- 29373434
TI  - Assessing Asymmetries in Change of Direction Speed Performance; Application of
      Change of Direction Deficit.
AB  - The aims of this study were to quantify asymmetries in change of direction (COD)
      performance via completion time and COD deficit, and determine its influence on
      asymmetry profiling of COD ability. A secondary aim was to evaluate the
      relationship between linear speed, 505 time and COD deficit. Forty-three youth
      netball athletes (age: 15.4 +/- 1.1 years, height: 1.71 +/- 0.06 m, mass: 63.3 +/
      6.6 kg) performed the 505 for both left and right limbs and a 10 m sprint test.
      Asymmetries in 505 completion time and COD deficit were quantified for dominant
      (D) (faster) and non-dominant (ND) (slower) directions. Paired sample t-tests
      revealed significant differences between D and ND directions for 505 time and COD
      deficit (p < 0.0001, g = -0.53 to -0.60). Substantially greater asymmetries for
      COD deficit were observed compared to 505 time (p < 0.0001, g = 1.03). Only two
      subjects displayed an asymmetry >=10% based on 505 times. Conversely, based on
      COD deficit, 21 subjects demonstrated asymmetries >=10%. Large significant
      associations were observed between 505 time and COD deficit (r = 0.500-0.593, p
      <= 0.002). Large significant inverse associations were demonstrated between 10 m
      sprint time and COD deficit (r = -0.539 to -0.633, p <= 0.001) indicating faster
      athletes had longer COD deficits. Nine subjects were classified differently for
      COD ability when comparing standardized scores for 505 time versus COD deficit.
      Quantification of asymmetries in COD ability should be based on COD deficits;
      inspection of 505 times only could lead to misinterpretations of an athlete's COD
      symmetry and COD ability. Faster youth netball athletes demonstrate longer COD
      deficits, thus, researchers and practitioners are encouraged to improve their
      youth netball athletes' ability to rapidly decelerate, change direction and
      reaccelerate from 180 degrees  turns.

PMID- 29373435
TI  - Match-play running demands and technical performance among elite Gaelic
      footballers: Does divisional status count?
AB  - The aim of the current study was to compare positional differences in running
      demands and technical performance variables among elite Gaelic football teams
      from separate Divisions. Data were obtained from a Division 1 (26.7 +/- 2.9
      years, 179.2 +/- 21.3 cm, 89.9 +/- 21.2 kg) and a Division 3 (25.7 +/- 3.5 years,
      183.0 +/- 4.7 cm, 84.4 +/- 6.5 kg) team. Match-play running variables were
      collected using 4-Hz global positioning system (GPS) units (VX Sport, New
      Zealand) (Match data sets; Division 1: n = 107, Division 3: n = 97). Selected
      variables assessed were high speed running distance (HSR) (>=17 km.h), number of
      high-speed efforts (HSE) (>= 17 km.h), relative high-speed distance (RHSD) (>= 17
      km.h; m.min) and percentage of time at high speed (%HS). Each variable was
      analysed across the 5 positional groups in Gaelic football (full-back, half-back,
      midfield, half-forward, full-forward). The same 25 competitive games were
      analysed using GPS and the Sports Code video analysis system (Sports Code Elite
      V9, Sportstec, NSW, Australia). Technical performance variables selected for
      analysis were total kick/hand passes, tackles, shots and percentage of time in
      possession. HSR running demands were differentiated between the divisions; the
      Division 3 team demonstrated significantly greater HSR, HSE, RHSD and %HS than
      the Division 1 team (p <0.05). Positional-specific analysis found that the
      Division 3 fullback and midfield positional lines had significantly greater HSR,
      RHSD and %HS than their Division 1 counterparts. The Division 1 team made a
      greater number of total tackles, with significantly more tackles in the middle
      third (p <0.05). The Division 3 team performed a significantly greater number of
      hand passes and unsuccessful shots per game (p <0.01). The results of the present
      study indicate that overall technical proficiency, rather than high-speed running
      profiles, differentiate Division 1 and 3 Gaelic football teams.

PMID- 29373436
TI  - Factors Associated With Pediatric Hospital-Acquired Pressure Injuries.
AB  - PURPOSE: The purpose of this study was to identify associations among pediatric
      patient characteristics (age and gender), hospital characteristics, inpatient
      unit characteristics (unit type, pressure injury prevention practices, and nurse
      staffing measures), and hospital-acquired pressure injuries (HAPIs) in a group of
      pediatric patients and in those determined to be at risk for pressure injury.
      DESIGN: A descriptive, correlational analysis of data from a large dataset.
      SUBJECTS AND SETTING: The sample comprised 39,984 children aged 1 day to 18 years
      of age from 678 pediatric units in 271 participating hospitals across the United
      States. METHODS: Data related to pressure injuries and prevention among pediatric
      patients from the National Database of Nursing Quality Indicators (NDNQI) were
      analyzed. All data were collected during the year 2012. Descriptive statistics
      were used to summarize the study sample. Hierarchical logistic regression
      analysis was used to analyze patient age and gender, unit type, pressure injury
      risk, prevention and staffing measures, and hospital characteristics associated
      with HAPI. RESULTS: The likelihood of a HAPI was more than 9 times higher among
      patients who were determined to be at risk for pressure injuries (odds ratio
      [OR]: 9.42, 95% confidence interval [CI]: 7.28-12.17, P < .001) compared to
      patients deemed not at risk. Hospital-acquired pressure injury was more likely to
      occur on pediatric critical care units (OR: 2.59, 95% CI: 1.28-5.26, P = .009)
      and rehabilitation units (OR: 4.05, 95% CI: 1.21-13.55, P = .02). Patients from
      hospitals that only provided care for children (OR: 2.6, 95% CI: 1.42-4.78, P =
      .002) were also more likely to be associated with HAPI compared to hospitals that
      provided care for adults and children. Among the 11,203 pediatric patients deemed
      at risk for pressure injuries, 95.8% received one or more prevention
      interventions. There were no prevention interventions associated with a lower
      occurrence of HAPI. CONCLUSIONS: Study findings support pressure injury risk
      assessment among pediatric patients and elucidates important information
      regarding pediatric unit and hospital characteristics associated with HAPI.

PMID- 29373437
TI  - Yield and Costs of Evaluating Children With Cyclic Vomiting Syndrome.
AB  - BACKGROUND AND OBJECTIVES: Cyclic vomiting syndrome (CVS) clinical guidelines
      recommend an algorithm of basic testing for standard patients, and more targeted
      testing, including laboratory and imaging studies, in the presence of specific
      red flags. The cost-effectiveness of this screening of children with suspected
      CVS is lacking. The objectives of this study are to determine whether screening
      studies in CVS patients results in diagnostic change and to estimate their
      healthcare cost. METHOD: Charts of patients (1-18 years) with suspected CVS were
      retrospectively reviewed at a single center. Results and cost of laboratory and
      imaging studies were analyzed. RESULTS: A total of 503 charts were reviewed from
      electronic medical records with the International Classification of Diseases-9
      (ICD-9) code 536.2 or search terms "CVS, cyclic vomiting, persistent
      emesis/vomiting, hyperemesis, or intractable/ periodic vomiting." Of these, 165
      (33%) had a diagnosis of CVS and 135 (82%) children (mean age 7.7 +/- 4.3; 73
      (54%) girls) met CVS criteria based on North American Society for Pediatric
      Gastroenterology, Hepatology and Nutrition diagnostic criteria. Of those meeting
      CVS criteria, 6 (4%) had a change in management based on the CVS screening
      evaluation. The mean cost of screening per patient that met CVS criteria was
      $6125.02 and the estimated total cost for all patients who met CVS criteria was
      $826,877.88. CONCLUSIONS: The screening metabolic laboratory results, pelvic
      ultrasound, magnetic resonance imaging, and upper endoscopy resulted in a
      diagnosis change in few patients screened for CVS. Most children who met criteria
      for CVS did not benefit from screening evaluation as results did not change
      clinical diagnosis or management, and were associated with higher cost.

PMID- 29373439
TI  - Psychological Factors and Outcomes in the Surgical Treatment of Pediatric
      Patients With Median Arcuate Ligament Syndrome.
AB  - OBJECTIVE: Median arcuate ligament syndrome (MALS) is a frequently overlooked
      cause of chronic abdominal pain (CAP), and results in many symptoms that mimic
      other gastrointestinal conditions that result in CAP. A small, but growing body
      of literature indicates that surgery improves quality of life (QOL) in patients
      with MALS. The purpose of the current study was to examine the psychological
      characteristics of pediatric patients with MALS to determine their prevalence and
      impact on surgical outcomes. METHODS: Thirty-two pediatric patients completed
      psychological assessments before surgery, and 6 months postsurgical intervention.
      Descriptive analyses and t tests were conducted to characterize the sample and
      compare psychosocial and QOL items. To explore possible associations between
      coping and ultimate changes in QOL, exploratory multiple regressions were
      conducted. RESULTS: Comorbid psychological conditions were common, occurring in
      about half the sample before and after surgery. Current pain significantly
      improved, as well as patient and parent-reported QOL constructs (Ps < 0.05).
      Parent-reported observations of patients using catastrophizing or helpless
      strategies to cope with pain before surgery was significantly associated with
      changes in patient and parent-reported QOL following surgery (Ps = 0.04).
      CONCLUSIONS: Comorbid psychological conditions are common in pediatric patients
      with MALS, and are maintained following surgery. While surgery improved pain and
      QOL, the need for presurgical psychological interventions for MALS is implicated.

PMID- 29373440
TI  - Esophageal Squamous Cell Papillomatosis Arising in Focal Dermal Hypoplasia in a 3
      Year-Old Girl.

PMID- 29373441
TI  - Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With
      Celiac Disease.
AB  - OBJECTIVES: Celiac disease (CD) is associated with thyroid autoimmunity and other
      autoimmune diseases. Data are, however, lacking regarding the relationship
      between thyroid autoimmunity and thyroid function, especially in regard to CD.
      Our aim was to investigate the impact of thyroid autoimmunity on thyroid function
      in 12-year-old children with CD compared to their healthy peers. METHODS: A case
      referent study was conducted as part of a CD screening of 12-year-olds. Our study
      included 335 children with CD and 1695 randomly selected referents. Thyroid
      autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb).
      Thyroid function was assessed with thyroid-stimulating hormone and free
      thyroxine. RESULTS: TPOAb positivity significantly increased the risk of
      developing hypothyroidism in all children. The odds ratios (with 95% confidence
      intervals) were 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening
      detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32)
      in all CD cases together. Among children with TPOAb positivity, hypothyroidism
      was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with
      CD (10/19) than in children without CD (12/46). CONCLUSIONS: The risk of thyroid
      dysfunction due to thyroid autoimmunity is larger for those with CD than their
      healthy peers. Our study indicates that a gluten-free diet does not reduce the
      risk of thyroid dysfunction. Further studies are required for improved
      understanding of the role of the gluten-free diet for the risk of autoimmune
      diseases in children with CD.

PMID- 29373442
TI  - Stroop Test Validation to Screen for Minimal Hepatic Encephalopathy in Pediatric
      Extrahepatic Portal Venous Obstruction.
AB  - OBJECTIVES: Minimal hepatic encephalopathy (MHE) has been reported in children
      with extrahepatic portal vein obstruction (EHPVO). MHE assessment is restricted
      to research situations as neuropsychiatric tests are time-intensive. Computerized
      Stroop Test (CST) has been used in cirrhotic adults for MHE screening. The study
      aims to assess MHE frequency in young Indian children with EHPVO and validate CST
      for MHE screening in pediatric EHPVO. METHODS: Thirty-seven children with EHPVO
      between 7 and 12 years of age and 37 age- and sex-matched controls were enrolled.
      Fasting plasma ammonia was measured. MHE was diagnosed by Revised Amsterdamse
      Kinder Intelligentie Test. The performance of a Tamil language version of CST in
      MHE screening was assessed. RESULTS: MHE was diagnosed in 18.9% (7/37) of EHPVO
      (EHPVO-MHE). Plasma ammonia levels were higher in EHPVO-MHE compared to EHPVO
      without MHE (EHPVO-No-MHE) but abnormal plasma ammonia levels are unsuitable for
      MHE screening. CST was administered in 35 EHPVO and 37 controls. EHPVO-MHE,
      compared to EHPVO-No-MHE, had longer "on time," "off time," "(on+off) time," and
      "(on-off) time." For MHE diagnosis, specificity and sensitivity of "(on+off)
      time" were 100% and 89.6% for a cutoff of >180.4 seconds (area under receiver
      operating characteristic = 0.97). CONCLUSIONS: In the absence of other risk
      factors for neurological insult or patent surgical shunts, MHE frequency in young
      Indian children with EHPVO, determined by Revised Amsterdamse Kinder
      Intelligentie Test, was lesser than in earlier studies. CST is suitable for MHE
      screening in clinical practice to select patients for neuropsychiatric
      evaluation.

PMID- 29373443
TI  - Evidence-Based Medicine: Abdominoplasty.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Differentiate between techniques for standard abdominoplasty and
      lipoabdominoplasty. 2. Assess patients for risk associated with abdominoplasty
      alone and combined with other procedures. 3. Implement newer modalities for
      abdominoplasty perioperative pain management. 4. Better understand the
      implications and techniques for rectus diastasis correction by rectus sheath
      plication. 5. Understand the evidence for eliminating the need for drains in
      abdominoplasty. SUMMARY: This update to past Maintenance of Certification
      articles offers new perspectives and builds on past knowledge regarding patient
      assessment, perioperative management, surgical execution, and complications of
      abdominoplasty.

PMID- 29373444
TI  - Preoperative Planning in the Surgical Correction of Tibial Nonunions and
      Malunions.
AB  - Three typical cases demonstrate the achievement of precision in the
      reconstruction of ununited fractures of the tibia by preliminary planning with
      the aid of tracings on roentgenograms, templates, and goniometer measurements.

PMID- 29373445
TI  - Valgus Slipped Capital Femoral Epiphysis: Pathophysiology of Motion and Results
      of Intracapsular Realignment.
AB  - OBJECTIVES: The purpose of this study was to report (1) a different but specific
      pattern of impingement in hips involved with valgus slipped capital femoral
      epiphysis (valgus SCFE) and (2) the results of surgical treatment using
      intracapsular realignment techniques. DESIGN: Case series. SETTING: Multiple
      academic centers. PATIENTS: Six patients with 8 involved hips referred for valgus
      alignment of proximal femoral epiphysis (valgus SCFE). INTERVENTION:
      Intracapsular realignment osteotomy combined with periacetabular osteotomy if
      needed. MAIN OUTCOME MEASUREMENT: The clinical and radiographical results and
      pathophysiology of motion. RESULTS: Eight hips in 6 patients were treated with
      subcapital (5 hips) or femoral neck (3 hips) osteotomy for realignment. The
      medially prominent metaphysis created an inclusive impingement at the anterior
      acetabular wall, whereas the high coxa valga favored impacting impingement at the
      posterior head-neck junction. The mean preoperative epiphyseal-shaft angle of
      110.5 (range 90-125 degrees) was reduced to 62 degrees (range 55-70 degrees)
      postoperatively. At the last follow-up, all but 1 hip were pain-free and
      impingement-free, with normal range of motion. One hip was replaced after
      repeated attempts of correction. The overall hip functional result using modified
      Merle d'Aubigne scoring system was excellent in 5 hips (18-16 points), good in 2
      hips (16-15 points), and poor in 1 hip (6 points). CONCLUSIONS: Impingement in
      valgus SCFE deformity is specific and complex. Anatomical realignment can lead to
      favorable results by the restoration of normal morphology and impingement-free
      range of motion. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29373446
TI  - Intraosseous Plating for the Management of Cortical Defects.
AB  - The management of fractures with segmental bone loss or abundant comminution on
      the far cortex is often complicated by deformity or frank hardware failure. Using
      plate constructs that rely on off-axis loading may not be sufficient to support
      the limb until healing occurs. There are a number of techniques to mitigate this
      problem, notably the use of intramedullary nails and bicolumnar plating of the
      fracture. These techniques are not always possible and do come with the biologic
      cost of additional surgery. In this article, the authors present a technique
      along with 2 case examples of using plates in an intraosseous location that was
      described by Dr Mast in his classic orthopaedic text. By placing these plates in
      the intramedullary space and then interdigitating fixation from the standard
      cortical plate, a rigid "I-beam" of fixation can be created to mitigate the
      eccentric loading placed on extraosseous plates. This technique is especially
      useful in situations in which intramedullary nails are precluded (comminuted
      intraarticular and some periprosthetic fractures).

PMID- 29373447
TI  - Does Posterior Fixation of Partially Unstable Open-Book Pelvic Ring Injuries
      Decrease Symphyseal Plate Failure? A Biomechanical Study.
AB  - OBJECTIVE: Recent clinical study suggests an advantage to adding an iliosacral
      screw to the anterior fixation construct for anteroposterior compression type-2
      (OTA/AO type 61-B1), partially unstable open-book pelvic ring injuries. Others
      have described stress examination to determine any required supplemental
      fixation. However, biomechanical studies investigating iliosacral fixation
      requirements for this injury are lacking. Our objective was to determine whether
      adding an iliosacral screw to symphyseal plate fixation decreases displacement in
      a well-defined open-book pelvic ring injury model. METHODS: An open-book pelvic
      ring injury was created in 10 human cadaveric pelves by unilaterally releasing
      the sacrospinous, sacrotuberous, and anterior sacroiliac ligaments plus
      transection of the pubic symphysis, approximating the classically described
      anteroposterior compression type-2 (APC-2) injury. Specimens were divided into 2
      groups: (1) symphyseal plating and (2) plating plus an iliosacral screw. Using a
      standard bilateral stance model loaded at 550 N, displacement measurements were
      obtained at 210,000 and 500,000 cycles. RESULTS: Three specimens failed before
      210,000 cycles because of technical errors and were excluded from analysis. For
      the remaining 7, there was no significant difference in displacement between the
      2 groups, and none sustained implant failure. Post hoc analysis showed that a
      large sample size (45/group) would be required to detect any difference with 80%
      power, indicating a small effect size with limited clinical application.
      CONCLUSIONS: Adding an iliosacral screw to the symphyseal plate fixation does not
      provide improved biomechanical outcome in classically described APC-2 injuries.
      Clinically, stress examination may be useful to determine the need for
      supplemental posterior fixation in APC-2 injuries.

PMID- 29373448
TI  - Endosteal Substitution With an Intramedullary Rod in Fractures of the Femur.
AB  - BACKGROUND: Morbid obesity and segmental fracture/bone loss are challenging
      problems in the treatment of fractures and nonunions of the distal femur. The use
      of an intramedullary rod as an endosteal substitute for a deficient medial cortex
      along with a lateral locked plate is 1-tool to combat these problems. This
      article describes the technique used and its results at a single Level 1 trauma
      center. METHODS: Retrospective chart and radiographic review of all patients
      treated for acute fractures and nonunions of the distal femur using endosteal
      substitution with an intramedullary nail and a lateral locked plate. Fixation
      construct was determined at the surgeon's discretion and was strongly influenced
      by bone loss and patient body habitus. RESULTS: Seven of 8 acute fractures and 8
      of 8 nonunions healed without an unplanned reoperation. There were no cases of
      secondary displacement after fixation, and only 1 unplanned reoperation in the
      study group. CONCLUSION: Endosteal substitution with an intramedullary rod and
      the use of a lateral locked plate provides the stability needed to allow bone
      healing under prolonged or supraphysiologic loads seen in morbid obesity or
      segmental bone loss. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 29373449
TI  - Soft Tissue Structures Differ in Patients With Prearthritic Hip Disease.
AB  - BACKGROUND: Clinically, understanding how the soft tissue envelope adapts to
      various forms of hip dysfunction could enhance both surgical and nonsurgical
      management. Very few studies have looked at soft tissue structures as
      preoperative discriminators between varying underlying etiologies of hip
      conditions. PURPOSE: To demonstrate that the magnetic resonance arthrography
      assessment of soft tissue structures of the hip will preoperatively differ in
      patients with different underlying hip joint diseases. METHODS: Fifty-seven
      patients who underwent preoperative magnetic resonance arthrography and
      corrective hip surgery were retrospectively identified yielding 3 groups: 17 with
      developmental dysplasia of the hip (DDH) (11 F, 6 M; mean age 35.1 years, range
      19.6-53.6); 20 with isolated labral tears (LTs) (17 F, 3 M; mean age 38.4 years,
      range 15.2-62.1), and 20 with cam-type femoroacetabular impingement (FAI) (11 F,
      9 M; mean age 38.8 years, range 18.9-51.2). Measurements of the hip labral
      length, capsule thickness, and psoas, rectus femoris, and gluteal muscle
      dimensions were performed, with normalization of the values for statistical
      analysis. RESULTS: The superior labral length was significantly greater in the
      DDH group [normalized value (NV): 0.30] compared with the FAI group (NV: 0.25, P
      < 0.05). In addition, the superior (12 o'clock) capsular thickness (NV: 0.24) was
      significantly greater compared with the LT group (NV: 0.15, P < 0.05) and the FAI
      group (NV: 0.16, P < 0.05). The DDH group also had a significantly greater
      anterior (3 o'clock) capsular thickness (NV: 0.18) compared with the LT group
      (NV: 0.13, P < 0.05). The transverse dimension of the rectus femoris was larger
      in the DDH group (NV: 1.39) compared with the FAI group (NV: 1.14, P < 0.05).
      CONCLUSION: An enlarged rectus femoris and thicker hip capsule as well as an
      enlarged labrum are characteristic findings in hip dysplasia. LEVEL OF EVIDENCE:
      Prognostic Level III. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29373450
TI  - Outcomes of Presumed Aseptic Long-Bone Nonunions With Positive Intraoperative
      Cultures Through a Single-Stage Surgical Protocol.
AB  - OBJECTIVE: To evaluate the outcomes of a single-stage surgical protocol to treat
      a presumed aseptic long-bone nonunion with positive intraoperative cultures
      obtained at the time of surgery. DESIGN: Retrospective comparative series.
      SETTING: Orthopaedic specialty hospital. PATIENTS AND METHODS: We retrospectively
      identified 77 patients with long-bone nonunions thought to be aseptic
      preoperatively, which grew bacteria from cultures obtained at the time of index
      nonunion surgery. INTERVENTION: Fifty (65%) patients underwent open debridement
      of the nonunion site followed by surgical stabilization through plates and
      screws. Twenty-seven (35%) patients underwent exchange nailing with canal
      reamings used for cultures. MAIN OUTCOME MEASUREMENT: Rate of radiographic union,
      time to clinical and radiographic union, nonunion rate after index nonunion
      surgery, and final union rate after revision procedures. RESULTS: Osseous union
      after the index nonunion surgery was achieved in 84% of the patients (65 of 77).
      Time to clinical union was 6.3 months (range, 1-24 months), and time to
      radiographic union was 7.4 months (range, 2-24 months). Eighteen percent (14 of
      77 patients) did not heal after the index nonunion surgery and required
      additional surgeries. The final union rate after revision surgery was 99% (76 of
      77 patients). CONCLUSIONS: Eighty-four percent of presumed aseptic nonunions of
      long-bone fractures with positive intraoperative cultures fully healed after a
      single-stage surgical protocol and long-term antibiotic when appropriate. When
      patients are diagnosed with a subclinical infected nonunion, they should be
      counseled about the higher likelihood of reoperation, but in most cases can
      expect excellent union rates after 1 additional surgery. LEVEL OF EVIDENCE:
      Prognostic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 29373451
TI  - Does Total Hip Arthroplasty Reduce the Risk of Secondary Surgery Following the
      Treatment of Displaced Acetabular Fractures in the Elderly Compared to Open
      Reduction Internal Fixation? A Pilot Study.
AB  - OBJECTIVES: The goal of open reduction and internal fixation (ORIF) is to
      anatomically reduce the facture and maintain a congruent hip joint. However, ORIF
      in the elderly is technically challenging. Therefore, there are advocates for
      acute total hip arthroplasty (THA) in this patient population. The primary
      purpose of this study was to evaluate the rate of revision surgery in elderly
      patients with acetabular fractures treated with ORIF or THA. The secondary
      purpose was to compare patient's self-reported functional outcomes. DESIGN:
      Retrospective review. SETTING: Two American College of Surgeons Level 1 trauma
      centers. PATIENTS/PARTICIPANTS: Thirty-three patients were treated with ORIF and
      37 were treated with THA. The mean follow-up was 22 months (range 6-89 months).
      Patients were interviewed, and radiographs were examined. INTERVENTION: Treatment
      of displaced acetabular fractures with either ORIF or THA. MAIN OUTCOME
      MEASUREMENTS: Need for reoperation. Harris Hip Score and SF-36 questionnaire.
      RESULTS: Those treated with ORIF had a higher rate of reoperation (10/33, 30%)
      compared with those treated with THA (5/37, 14%); however, this was not
      statistically significant (P = 0.12). Patients reported better bodily pain scores
      as measured by SF-36 (48 vs. 39, P = 0.04), and a trend toward improved function
      as measured by patient reported Harris Hip Scores (82 vs. 63, P = 0.06) in those
      treated with THA compared with ORIF. CONCLUSIONS: Acute reconstruction of
      acetabular fractures with THA in the geriatric population seems to compare
      favorably with ORIF, with a similar rate of complications, but with improved pain
      scores. In addition, there was a high rate of conversion to THA within 2 years of
      injury when patients were treated with ORIF. Acute THA as primary treatment in
      this patient population merits further, more controlled, comparative study. LEVEL
      OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29373452
TI  - Generic Preoperative Planning for Proximal Femoral Osteotomy in the Treatment of
      Nonunion of the Femoral Neck.
AB  - Despite improvements in surgical technique and overall patient care, failed
      treatment of fractures of the femoral neck persists. For the physiologically
      young patient, joint preservation is the preferred method of treatment.
      Unfortunately, the best treatment option, proximal femoral osteotomy, is fast
      becoming a lost art. Preoperative planning is critical in this regard. The
      described preoperative planning work flow is a reliable method for obtaining the
      desired deformity correction for a variety of proximal femoral malunions and
      nonunion. Revisiting the classic Pauwels osteotomy for femoral neck nonunion is
      an appropriate vehicle to supply the first link in resurrecting this treatment
      modality by providing a standardized preoperative planning protocol.

PMID- 29373453
TI  - Use of Spring Plates in Fixation of Comminuted Posterior Wall Acetabular
      Fractures.
AB  - OBJECTIVES: Surgical management of comminuted posterior wall acetabular fractures
      with marginal fragments remains difficult. The purpose of this study was to
      evaluate the use of spring plates as adjunctive fixation in comminuted posterior
      wall acetabular fractures. METHODS: A retrospective review of patients treated
      for posterior wall acetabular fractures with the use of customized spring plates
      as adjunctive fixation between 2000 and 2017 was performed. Patients were
      evaluated radiographically according to the grading criteria of Matta.
      Complications including subsequent revision surgery and hardware failure were
      recorded. RESULTS: Fifty-two patients underwent surgical fixation of posterior
      wall acetabular fractures with the use of customized 3.5-mm spring plates
      combined with posterior buttress compression plating over the spring plates as
      definitive fixation. Mean follow-up was 13.9 months (range: 3-140 months). Forty
      two patients had radiographic grades of excellent, with 6 good, 1 fair, and 3
      poor. There were no hardware complications. Five patients underwent revision
      surgery, including 4 patients (7.7%) who underwent a total hip arthroplasty due
      to advanced arthritis. CONCLUSIONS: The use of customized spring plates is a
      viable method of adjunctive fixation for comminuted posterior wall fractures with
      marginal fragmentation. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 29373454
TI  - Double Oblique Osteotomy: A Technique for Correction of Posttraumatic Deformities
      of the Distal Femur.
AB  - OBJECTIVE: To evaluate the outcomes of a double oblique osteotomy for the
      management of distal femoral malunions and a combination malunion/nonunion.
      DESIGN: Case series. SETTING: Level 1/2 hospital. PATIENTS/PARTICIPANTS: Ten
      patients with a mean age of 50 years (range 30-69 years) with posttraumatic
      deformities of the distal femur. INTERVENTION: A 2-level, length-sparing
      osteotomy was performed in accordance with a detailed preoperative plan for
      correction of the mechanical axis in a distal femoral deformity. MAIN OUTCOME
      MEASUREMENTS: Radiographic alignment and physical examination. RESULTS: Average
      length of follow-up was 26 months. The average coronal plane correction was 12
      degrees (range 4-20 degrees) for a residual coronal plane deformity average of 0
      degrees. The residual flexion deformity was less than 10 degrees in all cases.
      All rotational deformities were corrected to within 5 degrees of neutral. The
      average limb length correction was 1.6 cm (range 0.4-2.6 cm). Eight patients
      recovered without complication. One patient received bone grafting to achieve
      union, and a prominent angled blade plate was removed in another. An isolated
      saphenous nerve sensory deficit resolved spontaneously. CONCLUSIONS: The double
      oblique osteotomy is a reliable technique for the correction of multiplane
      deformities of the distal femur. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29373455
TI  - Routine Postoperative Computed Tomography Scans After Pelvic Fracture Fixation: A
      Necessity or a Luxury?
AB  - INTRODUCTION: There is no consensus regarding the postoperative radiology imaging
      protocol after pelvic fracture surgery. Some institutes routinely scan all
      patients after their surgery, others do not. The aim of this study was to assess
      the value of routine use of computed tomography (CT) scans after pelvic fracture
      surgery and to determine the sensitivity of conventional plain radiographs and
      intraoperative fluoroscopy in detecting metalwork malposition. PATIENTS AND
      METHODS: The radiographs and clinical notes of patients undergoing pelvic
      fracture surgery in the period between January 2010 and December 2015 were
      reviewed. Patients were categorized into 2 main groups: group A-patients whose
      fixation entailed the use of a sacroiliac (SI) screws and group B-patients whose
      fixation did not require an SI screw. Furthermore, the patients were classified
      according to the position of metalwork in their postoperative plain radiographs
      and perioperative fluoroscopy into 3 groups: (1) Safe: When there was no
      suspicion of metalwork malposition. (2) Suspicious: When there was some suspicion
      of malposition but radiographs were inconclusive. (3) Definite: When plain
      imaging showed a definite malposition. RESULTS: One hundred ninety-eight patients
      were included in this study (161 in group A and 37 in group B). In group A, 148
      (92%) were classified as safe, 10 were suspicious (6%), and 3 (2%) showed
      definite malposition. Of the fractures that were believed to be safe on plain
      radiographs, 78% were confirmed to be safe on CT scans, whereas 22% showed
      malpositioned metalwork, and 7 patients (4%) required a revision surgery. Plain
      radiographs showed a sensitivity of 27% in detecting metalwork malposition and a
      specificity of 99%. Increasing the number of screws significantly increased the
      risk of malposition and reoperation (P = 0.006 and 0.002 respectively). The plain
      images of group B were all classified as safe. The CT scans detected 2 cases with
      long metalwork protruding into the soft tissues, none of which required a
      revision surgery. CONCLUSION: Perioperative fluoroscopy and plain postoperative
      radiographs have a low sensitivity in detecting the metalwork malposition after
      pelvic fracture surgery. We recommend the use of routine postoperative CT scans
      in patients whose fixation entails the use of SI screws. In this series, routine
      scanning of patients who did not have SI screws added no significant clinical
      value. LEVEL OF EVIDENCE: Level IV Diagnostic. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 29373457
TI  - Prevalence of Posttraumatic Stress Disorder in Patients With Multiple Sclerosis.
AB  - Chronic and life-threatening illnesses, such as multiple sclerosis (MS), have
      been identified as significant stressors potentially triggering posttraumatic
      stress disorder (PTSD). The study aims to investigate the prevalence of PTSD
      according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition,
      Text Revision (DSM-IV-TR) criteria in a large sample of patients with MS. A total
      of 988 patients with MS were screened with the Impact of Event Scale-Revised, and
      then assessed with the PTSD module of the Structured Clinical Interview for DSM
      IV and with the Clinician-Administered PTSD Scale to confirm PTSD diagnosis.
      Posttraumatic symptoms were reported by 25.5% of the sample. A confirmed
      diagnosis of PTSD was found in 5.7% of patients, but prevalence could reach 8.5%,
      including also dropout patients. Further studies are needed to evaluate if
      adjustment disorder could better encompass the frequently encountered
      subthreshold posttraumatic stress symptoms and how clinicians can deal with these
      symptoms with appropriate interventions.

PMID- 29373458
TI  - Relationship Between the DSM-5 Anxious Distress Specifier and the Hamilton
      Depression Rating Scale Anxiety/Somatization Factor.
AB  - We examined the association between the Hamilton Depression Scale (HAMD) approach
      to classifying depressed patients into anxious and nonanxious subgroups and the
      Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
      anxious distress specifier subtyping. Two hundred two depressed patients were
      interviewed with semistructured diagnostic interviews. Patients were rated on the
      17-item HAMD and the Hamilton Anxiety Rating Scale and completed the Clinically
      Useful Anxiety Outcome Scale. Both approaches toward identifying anxiety in
      depressed patients resulted in most of the patients meeting the anxiety subtype.
      Both subtyping methods were significantly correlated with clinician-rated and
      self-report measures of anxiety, and scores on the anxiety scales were higher in
      the patients who met the anxious subtype. However, DSM-5 anxious distress
      subtyping was only marginally associated with the HAMD anxiety/somatization
      factor subtyping approach (k = 0.21), and dimensional scores were only moderately
      correlated (r = 0.50). These findings indicate that the DSM-5 and HAMD approaches
      toward identifying an anxious subtype of depression are not interchangeable.

PMID- 29373459
TI  - Differences in Mental Health Service Use Among Unemployed Veterans of Different
      Eras.
AB  - Mental disorders have been linked to unemployment among veterans. Improving
      mental health conditions, such as depression, can improve veteran employment
      outcomes. This study compared mental health treatment among unemployed Operation
      Enduring Freedom (OEF; in Afghanistan) and Operation Iraqi Freedom (OIF; in Iraq)
      veterans and veterans from other service eras. The study included 3165 unemployed
      veterans from six Veterans Affairs medical centers with a positive screen that
      indicates a possible mental disorder. Chi-squared tests and logistic regression
      analyses assessed whether veteran era was associated with mental health
      treatment. Unemployed OEF/OIF veterans were less likely to receive psychotropic
      medication and four or more psychotherapy sessions compared to veterans from
      other eras. Multivariable analyses controlling for age found associations based
      on younger age rather than era. Younger unemployed veterans received fewer mental
      health services, which is concerning because reducing mental health symptoms may
      increase employment and employment may reduce symptoms, which are key factors in
      reintegration into civilian life.

PMID- 29373456
TI  - Natural Medicines for Psychotic Disorders: A Systematic Review.
AB  - Patients with psychotic disorders regularly use natural medicines, although it is
      unclear whether these are effective and safe. The aim of this study was to
      provide an overview of evidence for improved outcomes by natural medicines. A
      systematic literature search was performed through Medline, PsycINFO, CINAHL, and
      Cochrane until May 2015. In 110 randomized controlled trials, evidence was found
      for glycine, sarcosine, N-acetylcysteine, some Chinese and ayurvedic herbs,
      ginkgo biloba, estradiol, and vitamin B6 to improve psychotic symptoms when added
      to antipsychotics. Ginkgo biloba and vitamin B6 seemed to reduce tardive
      dyskinesia and akathisia. Results on other compounds were negative or
      inconclusive. All natural agents, except reserpine, were well tolerated. Most
      study samples were small, study periods were generally short, and most results
      need replication. However, there is some evidence for beneficial effects of
      certain natural medicines.

PMID- 29373470
TI  - ERRATUM.

PMID- 29373460
TI  - Early low-anticoagulant desulfated heparin after traumatic brain injury: Reduced
      brain edema and leukocyte mobilization is associated with improved watermaze
      learning ability weeks after injury.
AB  - BACKGROUND: Unfractionated heparin administered immediately after traumatic brain
      injury (TBI) reduces brain leukocyte (LEU) accumulation, and enhances early
      cognitive recovery, but may increase bleeding after injury. It is unknown how non
      anticoagulant heparins, such as 2,3-O desulfated heparin (ODSH), impact post-TBI
      cerebral inflammation and long-term recovery. We hypothesized that ODSH after TBI
      reduces LEU-mediated brain inflammation and improves long-term neurologic
      recovery. METHODS: CD1 male mice (n = 66) underwent either TBI (controlled
      cortical impact [CCI]) or sham craniotomy. 2,3-O desulfated heparin (25 mg/kg
      [25ODSH] or 50 mg/kg [50ODSH]) or saline was administered for 48 hours after TBI
      in 46 animals. At 48 hours, intravital microscopy visualized rolling LEUs and
      fluorescent albumin leakage in the pial circulation, and the Garcia Neurologic
      Test assessed neurologic function. Brain edema (wet/dry ratio) was evaluated post
      mortem. In a separate group of animals (n = 20), learning/memory ability (% time
      swimming in the Probe platform quadrant) was assessed by the Morris Water Maze 17
      days after TBI. Analysis of variance with Bonferroni correction determined
      significance (p < 0.05). RESULTS: Compared with CCI (LEU rolling: 32.3 +/- 13.7
      LEUs/100 MUm per minute, cerebrovascular albumin leakage: 57.4 +/- 5.6%), both
      ODSH doses reduced post-TBI pial LEU rolling (25ODSH: 18.5 +/- 9.2 LEUs/100 MUm
      per minute, p = 0.036; 50ODSH: 7.8 +/- 3.9 LEUs/100 MUm per minute, p < 0.001)
      and cerebrovascular albumin leakage (25ODSH: 37.9 +/- 11.7%, p = 0.001, 50ODSH:
      32.3 +/- 8.7%, p < 0.001). 50ODSH also reduced injured cerebral hemisphere edema
      (77.7 +/- 0.4%) vs. CCI (78.7 +/- 0.4 %, p = 0.003). Compared with CCI, both ODSH
      doses improved Garcia Neurologic Test at 48 hours. Learning/memory ability (%
      time swimming in target quadrant) was lowest in CCI (5.9 +/- 6.4%) and
      significantly improved in the 25ODSH group (27.5 +/- 8.2%, p = 0.025).
      CONCLUSION: 2,3-O desulfated heparin after TBI reduces cerebral LEU recruitment,
      microvascular permeability and edema. 2,3-O desulfated heparin may also improve
      acute neurologic recovery leading to improved learning/memory ability weeks after
      injury.

PMID- 29373474
TI  - Association Between Enterovirus Infection and Asthma in Children: A 16-year
      Nationwide Population-based Cohort Study.
AB  - BACKGROUND: Both virus-induced asthma and enterovirus (EV) infection are common
      in children; however, the relationship between EV infection and virus-induced
      asthma has not been systematically investigated in a cohort study. This
      nationwide population-based cohort study investigated the association between EV
      infection and asthma. METHODS: We used data from the Taiwan National Health
      Insurance Research Database. The study sample consisted of insured children who
      were younger than 18 years and had EV infection between 1997 and 2013 and were
      followed until December 2013. We identified 36,935 children with EV infection and
      compared them based on 36,935 age-, sex-, urbanization- and income-matched
      controls to analyze the risk of subsequent asthma. Cox regression analyses were
      performed and adjusted for sex, age, urbanization, income, preterm labor and
      small for gestational age, perinatal complications, allergic rhinitis, allergic
      conjunctivitis, atopic dermatitis and bronchiolitis. RESULTS: The mean follow-up
      interval for all patients was 8.59 years (standard deviation = 4.35 years). The
      mean latency period between initial EV infection and onset of asthma was 2.77
      years (standard deviation = 2.43 years). EV infection was significantly
      associated with a higher incidence of asthma (hazard ratio = 1.65; 95% confidence
      interval: 1.60-1.71). CONCLUSIONS: A significant association was observed between
      EV infection and asthma in children. Health providers should be aware of the
      higher potential for children with EV to develop asthma in the future.

PMID- 29373475
TI  - Lessons From an Outbreak of Varicella Infection in Pediatric Hemato-oncology
      Patients.
AB  - BACKGROUND: Immunocompromised patients exposed to varicella may experience
      significant morbidity and a 7% mortality rate. Management and outcome of an
      outbreak of varicella infection among hospitalized pediatric hemato-oncology
      patients using the guidelines of the American Academy of Pediatrics Committee on
      Infectious Diseases are presented. METHODS: This retrospective study describes an
      outbreak of varicella infection between February 2011 and June 2011. Data were
      retrieved from the patients' files. Positive polymerase chain reaction results
      for varicella zoster virus from vesicular skin lesions were used for the
      diagnosis of varicella infection. RESULTS: Twelve pediatric hemato-oncology
      patients experienced 13 episodes of varicella infection, 11 underwent 1 episode
      each and 1 patient had 2 episodes. All exposed patients without immunity received
      varicella zoster immune globulins or intravenous immunoglobulin and were isolated
      as recommended by the guidelines. Infected patients received intravenous
      acyclovir. One patient with acute lymphoblastic leukemia at induction
      chemotherapy died. All the other patients survived. CONCLUSIONS: Our experience
      in the management of hospitalized immunocompromised patients exposed to varicella
      was that a positive IgG serology did not confer protection after exposure to
      varicella infection and thus can not serve as a marker for immunity. Unlike the
      isolation period sufficient for immunocompetent patients, crusted lesions can be
      contagious and thus require extended isolation for immunocompromised patients.
      Patients receiving rituximab are at greater risk of having persistent or
      recurrent disease. Studies with a larger sample size should be performed to
      better assess the management of immunocompromized patients exposed to varicella.

PMID- 29373476
TI  - Safety, Tolerability and Pharmacokinetics of MEDI8897, an Extended Half-life
      Single-dose Respiratory Syncytial Virus Prefusion F-targeting Monoclonal Antibody
      Administered as a Single Dose to Healthy Preterm Infants.
AB  - BACKGROUND: MEDI8897 is a recombinant human monoclonal antibody being developed
      for prophylaxis of serious respiratory syncytial virus (RSV) disease in all
      infants. METHODS: In this phase 1b/2a dose-escalation study, healthy preterm
      infants with a gestational age of 32-35 weeks were randomized to receive a single
      intramuscular injection of MEDI8897 (10, 25 or 50 mg) or placebo. Safety,
      pharmacokinetics, RSV-neutralizing antibody and antidrug antibody (ADA)
      assessments were performed during the 360-day follow-up period. Infants who
      experienced medically attended lower respiratory tract infections (LRTIs) were
      tested for RSV. RESULTS: MEDI8897 serum half-life ranged from 62.5-72.9 days. On
      day 151, 87% of infants in the 50 mg group had serum concentrations above the 90%
      effective concentration target level of 6.8 ug/mL, and 90% showed a >=4-fold rise
      from baseline in serum RSV-neutralizing antibody levels. Adverse events (AEs)
      were reported in 17 of 18 (94.4%) placebo and 66 of 71 (93.0%) MEDI8897
      recipients. Three MEDI8897 recipients experienced 5 serious AEs (3 LRTIs, 2
      febrile seizures). ADA was detected at any time postbaseline in 28.2% of MEDI8897
      recipients and at day 361 only in 26.5% of subjects. ADA response was not
      associated with AEs. Five (7%) MEDI8897 recipients experienced medically attended
      LRTIs through day 150; 1 tested positive for RSV (10 mg group). CONCLUSIONS:
      MEDI8897 had a favorable safety profile in healthy preterm infants. The extended
      half-life of MEDI8897 and demonstrated RSV-neutralizing activity support
      protection from RSV for the duration of a typical 5-month season after a single
      50 mg intramuscular (IM) dose.

PMID- 29373477
TI  - Refined Lab-score, a Risk Score Predicting Serious Bacterial Infection in Febrile
      Children Less Than 3 Years of Age.
AB  - BACKGROUND: The identification of serious bacterial infection (SBI) in children
      with fever without source remains a challenge. A risk score called Lab-score,
      based on C-reactive protein, procalcitonin and urinary dipstick results was
      derived to predict SBI. However, all biomarkers were initially dichotomized,
      leading to weak statistical reliability and lack of transportability across
      diverse settings. We aimed to refine and validate this risk-score algorithm.
      METHODS: The Lab-score was refined using a secondary analysis of a multicenter
      cohort study of children with fever without source via multilevel regression
      modeling. The external validation was conducted on data from a Canadian cohort
      study. RESULTS: Eight hundred seventy-seven children (24% SBI) were included for
      the derivation study, and 347 (16% SBI) for validation. Only C-reactive protein,
      procalcitonin, age and urinary dipstick remained independently associated with
      SBI. The model achieved an area under the receiver operating characteristic (ROC)
      curve of 0.94 (95% confidence interval [CI]: 0.93-0.96), which was significantly
      higher than any other isolated biomarker (P < 0.0001), and the original Lab-score
      (P < 0.0001). According to a decision curve analysis, the model yielded a better
      strategy than those based on independently considered biomarkers, or on the
      original Lab-score. The threshold analysis led to a cutoff that yielded 96% (95%
      CI: 92-98) sensitivity and 73% (95% CI: 70-77) specificity. The external
      validation found similar predictive abilities: 0.96 area under the ROC curve (95%
      CI: 0.93-0.99), 95% sensitivity (95% CI: 85-99) and 87% specificity (95% CI: 83
      91). CONCLUSION: The refined Lab-score demonstrated higher prediction ability for
      SBI than the original Lab-score, with promising wider applicability across
      settings. These results require validation in additional populations.

PMID- 29373478
TI  - Microvascular endothelial dysfunction is associated with albuminuria: the
      Maastricht Study.
AB  - OBJECTIVE: Albuminuria is thought to be a biomarker of microvascular and
      macrovascular endothelial dysfunction. However, direct evidence for an
      association of microvascular endothelial dysfunction with albuminuria is limited.
      In addition, experimental data suggest a stronger association of microvascular
      endothelial dysfunction with albuminuria in individuals with than in those
      without diabetes. METHODS: We examined cross-sectional associations of flicker
      light-induced retinal arteriolar dilation (n = 2095) and heat-induced skin
      hyperemia (n = 1508) with 24-h albuminuria in the population-based, diabetes
      enriched Maastricht Study. We used linear regression analyses to adjust for age,
      sex, type 2 diabetes, and cardiovascular disease risk factors. In addition, we
      tested for statistical interaction with type 2 diabetes. RESULTS: Median
      [interquartile range] albuminuria was 6.5 [3.9-11.6] mg/24 h and 8.2% had
      albuminuria at least 30 mg/24 h. After adjustment, albuminuria was 1.168 (95%
      confidence interval, 1.046-1.303) times greater in participants in the quartile
      with the smallest flicker light-induced retinal arteriolar dilation relative to
      those with the greatest dilation, and this association was stronger in
      participants with type 2 diabetes (Pinteraction < 0.10). Further, each 100
      percentage points lower heat-induced skin hyperemia was associated with a 1.022
      (1.010-1.035) times greater albuminuria in participants with type 2 diabetes,
      whereas it was not associated with albuminuria in nondiabetic participants
      (Pinteraction < 0.10). CONCLUSION: This is the first population-based study that
      provides direct evidence that microvascular endothelial dysfunction is associated
      with albuminuria, and that this association is stronger in individuals with than
      in those without type 2 diabetes.

PMID- 29373479
TI  - Orthostatic hypotension in older persons is not associated with cognitive
      functioning, features of cerebral damage or cerebral blood flow.
AB  - OBJECTIVE: Particularly in old age, orthostatic hypotension has been related to
      worse cognitive functioning, possibly caused by reduced cerebral blood flow
      (CBF). This study investigates whether orthostatic hypotension in older people is
      associated with cognitive dysfunction and, if so, whether this association is
      mediated by cerebral vascular damage and/or decreased CBF. METHODS: Four hundred
      and twenty participants of the Discontinuation of ANtihypertensive Treatment in
      Elderly People (DANTE) Study Leiden (mean age 81 years, all using
      antihypertensive medication and with mild cognitive deficits), and MRI data from
      214 participants of the nested DANTE MRI sub-study. Orthostatic hypotension was
      defined as either a SBP decrease at least 20 mmHg and/or a DBP decrease of at
      least 10 mmHg within 3 min of standing up. Cognitive functioning was assessed
      using a battery of six cognitive tests covering global cognition, memory
      function, executive function and psychomotor speed. Cerebral vascular damage and
      CBF were assessed using MRI. RESULTS: The prevalence of orthostatic hypotension
      was 47% (n = 199). Compared with the group without orthostatic hypotension,
      participants with orthostatic hypotension showed no differences in any of the
      cognitive functions, features of cerebral small vessel disease, microstructural
      integrity or CBF. CONCLUSION: In this population of older persons, the presence
      of orthostatic hypotension was not associated with decreased cognition. In
      addition, no differences were found in the supposedly underlying cerebral
      vascular mechanisms.

PMID- 29373480
TI  - The final word about LDL-cholesterol lowering.

PMID- 29373481
TI  - Hepatic actions of androgens in the regulation of metabolism.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent findings on
      hepatic actions of androgens in the regulation of protein, lipid and glucose
      metabolism. The rationale for liver-targeted testosterone use will be provided.
      RECENT FINDINGS: Liver-targeted testosterone administration, via the oral route,
      induces protein anabolic effect by reducing the rate of protein oxidation to a
      similar extent to that of systemic testosterone administration. Recent evidence
      indicates that testosterone exerts whole-body anabolic effect through inhibition
      of nitrogen loss via the hepatic urea cycle. Several hepatic effects of
      androgens, particularly on glucose metabolism, are direct and take place before
      any changes in body composition occur. This includes an increase in insulin
      secretion and sensitivity, and reduction in hepatic glucose output by
      testosterone. Furthermore, lack of testosterone in the liver exacerbates diet
      induced impairment in glucose metabolism. In the liver, androgens induce the full
      spectrum of metabolic changes through interaction with growth hormone or
      aromatization to estradiol. SUMMARY: Liver-targeted testosterone therapy may open
      up a new approach to achieve whole-body anabolism without systemic side-effects.
      Aromatizable androgens may be superior to nonaromatizable androgens in inducing a
      complex spectrum of direct, estrogen-mediated and other hormone-mediated effects
      of androgens.

PMID- 29373482
TI  - Rare monogenic causes of primary adrenal insufficiency.
AB  - PURPOSE OF REVIEW: Monogenic disorders play significant roles in the pathogenesis
      of childhood-onset primary adrenal insufficiency (PAI). The most common form of
      PAI is congenital adrenal hyperplasia (CAH), which includes the enzymatic defects
      of the steroidogenic pathway. This review focuses on less common forms of
      monogenic PAI (i.e. non-CAH monogenic PAI) with particular attention on their
      cause, clinical phenotypes and genetic epidemiology. RECENT FINDINGS: Non-CAH
      monogenic PAI can be classified into three major categories: first,
      adrenocorticotropic hormone resistance, second, impaired adrenal redox
      homeostasis and third, defective organogenesis of the adrenal glands. The
      clinical phenotypes of the mutation-carrying patients vary depending on the
      responsible gene, and they are partially explained by the tissue RNA expression
      patterns. Genetic epidemiology studies conducted in Turkey and Japan showed that
      about 80% of PAI of unknown cause was monogenic. SUMMARY: Genetic basis of non
      CAH monogenic PAI had been less clearly understood than CAH; however, significant
      advances have been made with use of new research techniques such as next
      generation sequencing. Understanding of these rare forms of PAI may contribute to
      clarifying the physiology and pathology of the adrenal glands.

PMID- 29373483
TI  - Spatial Distribution, Chemical Fraction and Fuzzy Comprehensive Risk Assessment
      of Heavy Metals in Surface Sediments from the Honghu Lake, China.
AB  - Spatial concentrations and chemical fractions of heavy metals (Cr, Cu, Pb, Zn and
      Cd) in 16 sampling sites from the Honghu Lake were investigated using an atomic
      absorption spectrophotometer and optimized BCR (the European Community Bureau of
      Reference) three-stage extraction procedure. Compared with the corresponding
      probable effect levels (PELs), adverse biological effects of the studied five
      sediment metals decreased in the sequence of Cr > Cu > Zn > Pb > Cd. Geo
      accumulation index (Igeo) values for Cr, Cu, Pb and Zn in each sampling site were
      at un-contamination level, while the values for Cd varied from un-contamination
      level to moderate contamination level. Spatially, the enrichment degree of Cd in
      lower part of the South Lake, the west part of the North Lake and the outlet were
      higher than the other parts of Honghu Lake. For metal chemical fractions, the
      proportions of the acid-extractable fraction of five metal contents were in the
      descending order: Cd, Cu, Zn, Pb and Cr. Cd had the highest bioaccessibility.
      Being the above indexes focused always on heavy metals' total content or chemical
      fraction in deterministic assessment system, which may confuse decision makers,
      the fuzzy comprehensive risk assessment method was established based on PEI
      (Potential ecological risk index), RAC (Risk assessment code) and fuzzy theory.
      Average comprehensive risks of heavy metals in sediments revealed the following
      orders: Cd (considerable risk) > Cu (moderate risk) > Zn (low risk) > Pb > Cr.
      Thus, Cd and Cu were determined as the pollutants of most concern. The central
      part of South Honghu Lake (S4, S5, S6, S9, S12 and S14), east part of the North
      Honghu Lake (S1) and outlet of outlet of the Honghu Lake (S10) were recommended
      as the priority control areas. Specifically, it is necessary to pay more
      attention to S1, S4, S5, S6, S9 and S16 when decision making for their calculated
      membership values (probabilities) of adjacent risk levels quite close.

PMID- 29373485
TI  - Control of the Singular Points Location for Miniature Switches with Magnetically
      Driven Contacts.
AB  - This paper presents and discusses usefulness and possibility of control of the
      singular points location of a driving magnetic field under as structure
      considerations as well as selection of energizing magnet systems for miniature
      electromagnetic switches. The sample results of theoretical analysis and
      experimental testing concern selected reed switches with normally open contacts
      as well as a developed miniature switch with a metallic ball contact. It must be
      noted that the switch with the contact performed by means of the metallic tiny
      ball can be effectively used both as a change-over switch as well as a detector
      of the energizing magnetic field distribution under designing and assembling of
      any electromagnetic contact device preferably with an increased degree of
      integration and miniaturization.

PMID- 29373484
TI  - Mechanisms of Cardiovascular Protection Associated with Intermittent Hypobaric
      Hypoxia Exposure in a Rat Model: Role of Oxidative Stress.
AB  - More than 140 million people live and works (in a chronic or intermittent form)
      above 2500 m worldwide and 35 million live in the Andean Mountains. Furthermore,
      in Chile, it is estimated that 55,000 persons work in high altitude shifts, where
      stays at lowlands and interspersed with working stays at highlands. Acute
      exposure to high altitude has been shown to induce oxidative stress in healthy
      human lowlanders, due to an increase in free radical formation and a decrease in
      antioxidant capacity. However, in animal models, intermittent hypoxia (IH) induce
      preconditioning, like responses and cardioprotection. Here, we aimed to describe
      in a rat model the responses on cardiac and vascular function to 4 cycles of
      intermittent hypobaric hypoxia (IHH). Twelve adult Wistar rats were randomly
      divided into two equal groups, a four-cycle of IHH, and a normobaric hypoxic
      control. Intermittent hypoxia was induced in a hypobaric chamber in four
      continuous cycles (1 cycle = 4 days hypoxia + 4 days normoxia), reaching a
      barometric pressure equivalent to 4600 m of altitude (428 Torr). At the end of
      the first and fourth cycle, cardiac structural, and functional variables were
      determined by echocardiography. Thereafter, ex vivo vascular function and
      biomechanical properties were determined in femoral arteries by wire myography.
      We further measured cardiac oxidative stress biomarkers (4-Hydroxy-nonenal, HNE;
      nytrotirosine, NT), reactive oxygen species (ROS) sources (NADPH and
      mitochondrial), and antioxidant enzymes activity (catalase, CAT; glutathione
      peroxidase, GPx, and superoxide dismutase, SOD). Our results show a higher
      ejection and shortening fraction of the left ventricle function by the end of the
      4th cycle. Further, femoral vessels showed an improvement of vasodilator capacity
      and diminished stiffening. Cardiac tissue presented a higher expression of
      antioxidant enzymes and mitochondrial ROS formation in IHH, as compared with
      normobaric hypoxic controls. IHH exposure determines a preconditioning effect on
      the heart and femoral artery, both at structural and functional levels,
      associated with the induction of antioxidant defence mechanisms. However,
      mitochondrial ROS generation was increased in cardiac tissue. These findings
      suggest that initial states of IHH are beneficial for cardiovascular function and
      protection.

PMID- 29373486
TI  - Green Synthesis of Fluorescent Palladium Nanoclusters.
AB  - Metal nanoclusters, with dimensions between atomic and nanoparticles, have
      attracted a great deal of attention due to their significantly unusual
      properties. Water-soluble palladium nanoclusters (Pd NCs) with blue-green
      fluorescence were synthesized by a water bath heating method, with methionine as
      a stabilizer and ascorbic acid as a reducing agent. We investigated the optimal
      synthesis conditions, stability, and pH response of the obtained products in
      detail. The synthesized materials were characterized by ultraviolet-absorption
      spectroscopy, fluorescence spectroscopy, high-resolution transmission electron
      microscopy, and atomic force microscopy. These experimental results showed that
      the Pd NCs had a small size of ~1.91 nm, with a uniform size distribution.
      Additionally, the Pd NCs emitted blue-green fluorescence under ultraviolet light
      with a quantum yield of 5.47%. Notably, both stabilizers and reducing agents used
      in this synthesis method are nutrients for humans, non-toxic, and harmless. This
      method could be viewed as a biologically friendly and green way of preparing
      fluorescent metal nanoclusters. The as-prepared fluorescent Pd NCs also possessed
      excellent fluorescence detection ability and were very sensitive to low
      concentrations of hemoglobin, with a linear response in the range of 0.25-3.5 MUM
      and a detection limit of 50 nM.

PMID- 29373487
TI  - The Mechanical Properties of Biocompatible Apatite Bone Cement Reinforced with
      Chemically Activated Carbon Fibers.
AB  - Calcium phosphate cement (CPC) is a well-established bone replacement material in
      dentistry and orthopedics. CPC mimics the physicochemical properties of natural
      bone and therefore shows excellent in vivo behavior. However, due to their
      brittleness, the application of CPC implants is limited to non-load bearing
      areas. Generally, the fiber-reinforcement of ceramic materials enhances fracture
      resistance, but simultaneously reduces the strength of the composite. Combining
      strong C-fiber reinforcement with a hydroxyapatite to form a CPC with a chemical
      modification of the fiber surface allowed us to adjust the fiber-matrix interface
      and consequently the fracture behavior. Thus, we could demonstrate enhanced
      mechanical properties of CPC in terms of bending strength and work of fracture to
      a strain of 5% (WOF5). Hereby, the strength increased by a factor of four from
      9.2 +/- 1.7 to 38.4 +/- 1.7 MPa. Simultaneously, the WOF5 increased from 0.02 +/-
      0.004 to 2.0 +/- 0.6 kJ?m-2, when utilizing an aqua regia/CaCl2 pretreatment. The
      cell proliferation and activity of MG63 osteoblast-like cells as biocompatibility
      markers were not affected by fiber addition nor by fiber treatment. CPC
      reinforced with chemically activated C-fibers is a promising bone replacement
      material for load-bearing applications.

PMID- 29373488
TI  - A Review of Eight High-Priority, Economically Important Viral Pathogens of
      Poultry within the Caribbean Region.
AB  - Viral pathogens cause devastating economic losses in poultry industries
      worldwide. The Caribbean region, which boasts some of the highest rates of
      poultry consumption in the world, is no exception. This review summarizes
      evidence for the circulation and spread of eight high-priority, economically
      important poultry viruses across the Caribbean region. Avian influenza virus
      (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV),
      infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV),
      infectious bursal disease virus (IBDV), fowl adenovirus group 1 (FADV Gp1), and
      egg drop syndrome virus (EDSV) were selected for review. This review of
      serological, molecular, and phylogenetic studies across Caribbean countries
      reveals evidence for sporadic outbreaks of respiratory disease caused by
      notifiable viral pathogens (AIV, IBV, NDV, and ILTV), as well as outbreaks of
      diseases caused by immunosuppressive viral pathogens (IBDV and FADV Gp1). This
      review highlights the need to strengthen current levels of surveillance and
      reporting for poultry diseases in domestic and wild bird populations across the
      Caribbean, as well as the need to strengthen the diagnostic capacity and
      capability of Caribbean national veterinary diagnostic laboratories.

PMID- 29373489
TI  - A Novel Inverse Solution of Contact Force Based on a Sparse Tactile Sensor Array.
AB  - High-density tactile sensing has been pursued for humanoid robotic hands to
      obtain contact force information while the elastomer skin cover is traditionally
      considered to impair the force discrimination. In this work, we try to utilize
      the diffusion effect of the elastomer cover to identify an arbitrary contact
      force load just based on a sparse tactile sensor array. By numerical analysis, we
      proved the monotonous relation between the Pearson's correlation coefficient and
      the relative distance of two single-force loads. Then, we meshed the elastomer
      surface and conducted the calibration load process to establish the calibration
      database of the sensing outputs. Afterwards, we applied the correlation method to
      the database and the sensing output of the unknown load to determine its location
      and intensity. For validation tests of the proposed method, we designed and
      fabricated a 3 * 3 sparse tactile sensor array with flat elastomer cover and
      established an automatic three-axis loading system. The validation tests were
      implemented including 100 random points with force intensity ranging from 0.1 to
      1 N. The test results show that the method has good accuracy of detecting force
      load with the mean location error of 0.46 mm and the mean intensity error of
      0.043 N, which meets the basic requirements of tactile sensing. Therefore, it is
      feasible for the sparse tactile sensor array to realize high-density load
      detection.

PMID- 29373490
TI  - Cellular Interaction and Tumoral Penetration Properties of Cyclodextrin
      Nanoparticles on 3D Breast Tumor Model.
AB  - Amphiphilic cyclodextrins are biocompatible oligosaccharides that can be used for
      drug delivery especially for the delivery of drugs with solubility problems
      thanks to their unique molecular structures. In this paper, Paclitaxel was used
      as a model anticancer drug to determine the inclusion complex properties of
      amphiphilic cyclodextrins with different surface charge. Paclitaxel-loaded
      cyclodextrin nanoparticles were characterized in terms of mean particle diameter,
      zeta potential, encapsulation efficacy, drug release profile and cell culture
      studies. It was determined that the nanoparticles prepared from the inclusion
      complex according to characterization studies have a longer release profile than
      the conventionally prepared nanoparticles. In order to mimic the tumor
      microenvironment, breast cancer cells and healthy fibroblast cells were used in 3
      dimensional (3D) cell culture studies. It was determined that the activities of
      nanoparticles prepared by conventional methods behave differently in 2
      dimensional (2D) and 3D cell cultures. In addition, it was observed that the
      nanoparticles prepared from the inclusion complex have a stronger anti-tumoral
      activity in the 3D multicellular tumor model than the drug solution. Furthermore,
      polycationic amphiphilic cyclodextrin nanoparticles can diffuse and penetrate
      through multilayer cells in a 3D tumor model, which is crucial for an eventual
      antitumor effect.

PMID- 29373491
TI  - Microservices in Web Objects Enabled IoT Environment for Enhancing Reusability.
AB  - In the ubiquitous Internet of Things (IoT) environment, reusing objects instead
      of creating new one has become important in academics and industries. The
      situation becomes complex due to the availability of a huge number of connected
      IoT objects, and each individual service creates a new object instead of reusing
      the existing one to fulfill a requirement. A well-standard mechanism not only
      improves the reusability of objects but also improves service modularity and
      extensibility, and reduces cost. Web Objects enabled IoT environment applies the
      principle of reusability of objects in multiple IoT application domains through
      central objects repository and microservices. To reuse objects with microservices
      and to maintain a relationship with them, this study presents an architecture of
      Web of Objects platform. In the case of a similar request for an object, the
      already instantiated object that exists in the same or from other domain can be
      reused. Reuse of objects through microservices avoids duplications, and reduces
      time to search and instantiate them from their registries. Further, this article
      presents an algorithm for microservices and related objects discovery that
      considers the reusability of objects through the central objects repository. To
      support the reusability of objects, the necessary algorithm for objects matching
      is also presented. To realize the reusability of objects in Web Objects enabled
      IoT environment, a prototype has been designed and implemented based on a use
      case scenario. Finally, the results of the prototype have been analyzed and
      discussed to validate the proposed approach.

PMID- 29373493
TI  - Traditional Malian Solid Foods Made from Sorghum and Millet Have Markedly Slower
      Gastric Emptying than Rice, Potato, or Pasta.
AB  - From anecdotal evidence that traditional African sorghum and millet foods are
      filling and provide sustained energy, we hypothesized that gastric emptying rates
      of sorghum and millet foods are slow, particularly compared to non-traditional
      starchy foods (white rice, potato, wheat pasta). A human trial to study gastric
      emptying of staple foods eaten in Bamako, Mali was conducted using a carbon-13
      (13C)-labelled octanoic acid breath test for gastric emptying, and subjective pre
      test and satiety response questionnaires. Fourteen healthy volunteers in Bamako
      participated in a crossover design to test eight starchy staples. A second
      validation study was done one year later in Bamako with six volunteers to correct
      for endogenous 13C differences in the starches from different sources. In both
      trials, traditional sorghum and millet foods (thick porridges and millet
      couscous) had gastric half-emptying times about twice as long as rice, potato, or
      pasta (p < 0.0001). There were only minor changes due to the 13C correction. Pre
      test assessment of millet couscous and rice ranked them as more filling and
      aligned well with postprandial hunger rankings, suggesting that a preconceived
      idea of rice being highly satiating may have influenced subjective satiety
      scoring. Traditional African sorghum and millet foods, whether viscous in the
      form of a thick porridge or as non-viscous couscous, had distinctly slow gastric
      emptying, in contrast to the faster emptying of non-traditional starchy foods,
      which are popular among West African urban consumers.

PMID- 29373495
TI  - Indirect Reconstruction of Pore Morphology for Parametric Computational
      Characterization of Unidirectional Porous Iron.
AB  - This paper addresses the problem of reconstructing realistic, irregular pore
      geometries of lotus-type porous iron for computer models that allow for simple
      porosity and pore size variation in computational characterization of their
      mechanical properties. The presented methodology uses image-recognition
      algorithms for the statistical analysis of pore morphology in real material
      specimens, from which a unique fingerprint of pore morphology at a certain
      porosity level is derived. The representative morphology parameter is introduced
      and used for the indirect reconstruction of realistic and statistically
      representative pore morphologies, which can be used for the generation of
      computational models with an arbitrary porosity. Such models were subjected to
      parametric computer simulations to characterize the dependence of engineering
      elastic modulus on the porosity of lotus-type porous iron. The computational
      results are in excellent agreement with experimental observations, which confirms
      the suitability of the presented methodology of indirect pore geometry
      reconstruction for computational simulations of similar porous materials.

PMID- 29373492
TI  - Do Neuroendocrine Peptides and Their Receptors Qualify as Novel Therapeutic
      Targets in Osteoarthritis?
AB  - Joint tissues like synovium, articular cartilage, meniscus and subchondral bone,
      are targets for neuropeptides. Resident cells of these tissues express receptors
      for various neuroendocrine-derived peptides including proopiomelanocortin (POMC)
      derived peptides, i.e., alpha-melanocyte-stimulating hormone (alpha-MSH),
      adrenocorticotropin (ACTH) and beta-endorphin (beta-ED), and sympathetic
      neuropeptides like vasoactive intestinal peptide (VIP) and neuropeptide y (NPY).
      Melanocortins attained particular attention due to their immunomodulatory and
      anti-inflammatory effects in several tissues and organs. In particular, alpha
      MSH, ACTH and specific melanocortin-receptor (MCR) agonists appear to have
      promising anti-inflammatory actions demonstrated in animal models of
      experimentally induced arthritis and osteoarthritis (OA). Sympathetic
      neuropeptides have obtained increasing attention as they have crucial trophic
      effects that are critical for joint tissue and bone homeostasis. VIP and NPY are
      implicated in direct and indirect activation of several anabolic signaling
      pathways in bone and synovial cells. Additionally, pituitary adenylate cyclase
      activating polypeptide (PACAP) proved to be chondroprotective and, thus, might be
      a novel target in OA. Taken together, it appears more and more likely that the
      anabolic effects of these neuroendocrine peptides or their respective receptor
      agonists/antagonists may be exploited for the treatment of patients with
      inflammatory and degenerative joint diseases in the future.

PMID- 29373494
TI  - Microtubule-Actin Crosslinking Factor 1 and Plakins as Therapeutic Drug Targets.
AB  - Plakins are a family of seven cytoskeletal cross-linker proteins (microtubule
      actin crosslinking factor 1 (MACF), bullous pemphigoid antigen (BPAG1)
      desmoplakin, envoplakin, periplakin, plectin, epiplakin) that network the three
      major filaments that comprise the cytoskeleton. Plakins have been found to be
      involved in disorders and diseases of the skin, heart, nervous system, and cancer
      that are attributed to autoimmune responses and genetic alterations of these
      macromolecules. Despite their role and involvement across a spectrum of several
      diseases, there are no current drugs or pharmacological agents that specifically
      target the members of this protein family. On the contrary, microtubules have
      traditionally been targeted by microtubule inhibiting agents, used for the
      treatment of diseases such as cancer, in spite of the deleterious toxicities
      associated with their clinical utility. The Research Collaboratory for Structural
      Bioinformatics (RCSB) was used here to identify therapeutic drugs targeting the
      plakin proteins, particularly the spectraplakins MACF1 and BPAG1, which contain
      microtubule-binding domains. RCSB analysis revealed that plakin proteins had 329
      ligands, of which more than 50% were MACF1 and BPAG1 ligands and 10 were
      documented, clinically or experimentally, to have several therapeutic
      applications as anticancer, anti-inflammatory, and antibiotic agents.

PMID- 29373496
TI  - The Neuroscience of Growth Mindset and Intrinsic Motivation.
AB  - Our actions can be triggered by intentions, incentives or intrinsic values.
      Recent neuroscientific research has yielded some results about the growth mindset
      and intrinsic motivation. With the advances in neuroscience and motivational
      studies, there is a global need to utilize this information to inform educational
      practice and research. Yet, little is known about the neuroscientific interplay
      between growth mindset and intrinsic motivation. This paper attempts to draw on
      the theories of growth mindset and intrinsic motivation, together with
      contemporary ideas in neuroscience, outline the potential for neuroscientific
      research in education. It aims to shed light on the relationship between growth
      mindset and intrinsic motivation in terms of supporting a growth mindset to
      facilitate intrinsic motivation through neural responses. Recent empirical
      research from the educational neuroscience perspective that provides insights
      into the interplay between growth mindset and intrinsic motivation will also be
      discussed.

PMID- 29373497
TI  - Ultrafast Chemistry of Water Radical Cation, H2O*+, in Aqueous Solutions.
AB  - Oxidation reactions by radicals constitute a very important class of chemical
      reactions in solution. Radiation Chemistry methods allow producing, in a
      controlled way, very reactive oxidizing radicals, such as OH*, CO3*-, NO3*, SO4*
      , and N3*. Although the radical cation of water, H2O*+, with a very short
      lifetime (shorter than 1 ps) is the precursor of these radicals in aqueous
      solutions, its chemistry is usually known to be limited to the reaction of proton
      transfer by forming OH* radical. Herein, we stress situations where H2O*+
      undergoes electron transfer reaction in competition with proton transfer.

PMID- 29373498
TI  - Defining Multidrug Resistance of Gram-Negative Bacteria in the Dutch-German
      Border Region-Impact of National Guidelines.
AB  - Preventing the spread of multidrug-resistant Gram-negative bacteria (MDRGNB) is a
      public health priority. However, the definition of MDRGNB applied for planning
      infection prevention measures such as barrier precautions differs depending on
      national guidelines. This is particularly relevant in the Dutch-German border
      region, where patients are transferred between healthcare facilities located in
      the two different countries, because clinicians and infection control personnel
      must understand antibiograms indicating MDRGNB from both sides of the border and
      using both national guidelines. This retrospective study aimed to compare
      antibiograms of Gram-negative bacteria and classify them using the Dutch and
      German national standards for MDRGNB definition. A total of 31,787 antibiograms
      from six Dutch and four German hospitals were classified. Overall, 73.7% were no
      MDRGNB according to both guidelines. According to the Dutch and German guideline,
      7772/31,787 (24.5%) and 4586/31,787 (12.9%) were MDRGNB, respectively (p <
      0.0001). Major divergent classifications were observed for extended-spectrum beta
      lactamase (ESBL) -producing Enterobacteriaceae, non-carbapenemase-producing
      carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa and
      Stenotrophomonas maltophilia. The observed differences show that medical staff
      must carefully check previous diagnostic findings when patients are transferred
      across the Dutch-German border, as it cannot be assumed that MDRGNB requiring
      special hygiene precautions are marked in the transferred antibiograms in
      accordance with both national guidelines.

PMID- 29373499
TI  - A Proposal for IoT Dynamic Routes Selection Based on Contextual Information.
AB  - The Internet of Things (IoT) is based on interconnection of intelligent and
      addressable devices, allowing their autonomy and proactive behavior with Internet
      connectivity. Data dissemination in IoT usually depends on the application and
      requires context-aware routing protocols that must include auto-configuration
      features (which adapt the behavior of the network at runtime, based on context
      information). This paper proposes an approach for IoT route selection using fuzzy
      logic in order to attain the requirements of specific applications. In this case,
      fuzzy logic is used to translate in math terms the imprecise information
      expressed by a set of linguistic rules. For this purpose, four Objective
      Functions (OFs) are proposed for the Routing Protocol for Low Power and Loss
      Networks (RPL); such OFs are dynamically selected based on context information.
      The aforementioned OFs are generated from the fusion of the following metrics:
      Expected Transmission Count (ETX), Number of Hops (NH) and Energy Consumed (EC).
      The experiments performed through simulation, associated with the statistical
      data analysis, conclude that this proposal provides high reliability by
      successfully delivering nearly 100% of data packets, low delay for data delivery
      and increase in QoS. In addition, an 30% improvement is attained in the network
      life time when using one of proposed objective function, keeping the devices
      alive for longer duration.

PMID- 29373500
TI  - Evaluation of Two-Diabetes Related microRNAs Suitability as Earlier Blood
      Biomarkers for Detecting Prediabetes and type 2 Diabetes Mellitus.
AB  - Increased the incidence of prediabetes and type 2 diabetes (T2D) worldwide raises
      an urgent need to develop effective tools for early disease detection to
      facilitate future preventive interventions and improve patient's care. We
      evaluated the suitability of diabetes-related miR-375 and miR-9 as earlier
      biomarkers for detecting prediabetes and T2D.TaqMan-based RT-qPCR was used to
      quantify the expression of miRNAs in peripheral blood of 30 prediabetes patients,
      30 T2D patients and 30 non-diabetic healthy controls. Compared to controls, miR
      375 and miR-9 were expressed at higher levels in prediabetes patients and
      progressively more enriched in T2D patients. Both miRNAs were directly associated
      with the presence of prediabetes and T2D independently of known risk factors to
      T2D and miR-375 was independently associated with the development of T2D. Both
      miRNAs were positively correlated with the glycemic status and other T2D risk
      factors. The ROC analysis indicated good diagnostic abilities for miR-375 to
      distinguish overall patients from control and prediabetes from T2D patients.
      Whereas, miR-9 showed lower values and borderline significance in discriminating
      the subject groups. The combination of miRNAs enhanced the predictability to
      discriminate patients from control. These results suggest that miR-375 and miR-9
      are associated with the susceptibility to developing T2D and miR-375 alone or in
      combination with miR-9 could serve as biomarkers for early detection of
      prediabetes and T2D.

PMID- 29373502
TI  - Label-Free Aptasensor for Lysozyme Detection Using Electrochemical Impedance
      Spectroscopy.
AB  - This research develops a label-free aptamer biosensor (aptasensor) based on
      graphite-epoxy composite electrodes (GECs) for the detection of lysozyme protein
      using Electrochemical Impedance Spectroscopy (EIS) technique. The chosen
      immobilization technique was based on covalent bonding using carbodiimide
      chemistry; for this purpose, carboxylic moieties were first generated on the
      graphite by electrochemical grafting. The detection was performed using
      [Fe(CN)6]3-/[Fe(CN)6]4- as redox probe. After recording the frequency response,
      values were fitted to its electric model using the principle of equivalent
      circuits. The aptasensor showed a linear response up to 5 uM for lysozyme and a
      limit of detection of 1.67 uM. The sensitivity of the established method was
      0.090 uM-1 in relative charge transfer resistance values. The interference
      response by main proteins, such as bovine serum albumin and cytochrome c, has
      been also characterized. To finally verify the performance of the developed
      aptasensor, it was applied to wine analysis.

PMID- 29373501
TI  - Impact & Blast Traumatic Brain Injury: Implications for Therapy.
AB  - Traumatic brain injury (TBI) is one of the most frequent causes of combat
      casualties in Operations Iraqi Freedom (OIF), Enduring Freedom (OEF), and New
      Dawn (OND). Although less common than combat-related blast exposure, there have
      been significant numbers of blast injuries in civilian populations in the United
      States. Current United States Department of Defense (DoD) ICD-9 derived diagnoses
      of TBI in the DoD Health Care System show that, for 2016, severe and moderate
      TBIs accounted for just 0.7% and 12.9%, respectively, of the total of 13,634
      brain injuries, while mild TBIs (mTBIs) accounted for 86% of the total. Although
      there is a report that there are differences in the frequency of long-term
      complications in mTBI between blast and non-blast TBIs, clinical presentation is
      classified by severity score rather than mechanism because severity scoring is
      associated with prognosis in clinical practice. Blast TBI (bTBI) is unique in its
      pathology and mechanism, but there is no treatment specific for bTBIs-these
      patients are treated similarly to TBIs in general and therapy is tailored on an
      individual basis. Currently there is no neuroprotective drug recommended by the
      clinical guidelines based on evidence.

PMID- 29373503
TI  - Interrupting Prolonged Sitting with Regular Activity Breaks does not Acutely
      Influence Appetite: A Randomised Controlled Trial.
AB  - Regular activity breaks increase energy expenditure; however, this may promote
      compensatory eating behaviour. The present study compared the effects of regular
      activity breaks and prolonged sitting on appetite. In a randomised, cross-over
      trial, 36 healthy adults (BMI (Body Mass Index) 23.9 kg/m2 (S.D. = 3.9))
      completed four, two-day interventions: two with prolonged sitting (SIT), and two
      with sitting and 2 min of walking every 30 min (RAB). Standardized meals were
      provided throughout the intervention, with an ad libitum meal at the end of Day
      2. Appetite and satiety were assessed throughout both days of each intervention
      using five visual analogue scales. The five responses were combined into a single
      appetite response at each time point. The area under the appetite response curve
      (AUC) was calculated for each day. Intervention effects for appetite response AUC
      and ad libitum meal intake were tested using linear mixed models. Appetite AUC
      did not differ between interventions (standardised effect of RAB compared to SIT:
      Day 1: 0.11; 95% CI: -0.28, 0.06; p = 0.212; Day 2: 0.04; 95% CI: -0.15, 0.24; p
      = 0.648). There was no significant difference in energy consumed at the ad
      libitum lunch meal on Day 2 between RAB and SIT. Interrupting prolonged sitting
      with regular activity breaks does not acutely influence appetite or volume of
      food consumed, despite inferred increases in energy expenditure. Longer-term
      investigation into the effects of regular activity breaks on energy balance is
      warranted.

PMID- 29373504
TI  - The Response of HeLa Cells to Fluorescent NanoDiamond Uptake.
AB  - Fluorescent nanodiamonds are promising probes for nanoscale magnetic resonance
      measurements. Their physical properties predict them to have particularly useful
      applications in intracellular analysis. Before using them in intracellular
      experiments however, it should be clear whether diamond particles influence cell
      biology. While cytotoxicity has already been ruled out in previous studies, we
      consider the non-fatal influence of fluorescent nanodiamonds on the formation of
      reactive oxygen species (an important stress indicator and potential target for
      intracellular sensing) for the first time. We investigated the influence of
      different sizes, shapes and concentrations of nanodiamonds on the genetic and
      protein level involved in oxidative stress-related pathways of the HeLa cell, an
      important model cell line in research. The changes in viability of the cells and
      the difference in intracellular levels of free radicals, after diamond uptake,
      are surprisingly small. At lower diamond concentrations, the cellular metabolism
      cannot be distinguished from that of untreated cells. This research supports the
      claims of non-toxicity and includes less obvious non-fatal responses. Finally, we
      give a handhold concerning the diamond concentration and size to use for non
      toxic, intracellular measurements in favour of (cancer) research in HeLa cells.

PMID- 29373505
TI  - Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the
      Endocytosis Pathway Analysis and Intracellular Localization.
AB  - Using renewable and biocompatible natural-based resources to construct functional
      biomaterials has attracted great attention in recent years. In this work, we
      successfully prepared a series of steroid-based cationic lipids by integrating
      various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile
      and efficient synthetic approach. The plasmid DNA (pDNA) binding affinity of the
      steroid-based cationic lipids, average particle sizes, surface potentials,
      morphologies and stability of the steroid-based cationic lipids/pDNA lipoplexes
      were disclosed to depend largely on the steroid skeletons. Cellular evaluation
      results revealed that cytotoxicity and gene transfection efficiency of the
      steroid-based cationic lipids in H1299 and HeLa cells strongly relied on the
      steroid hydrophobes. Interestingly, the steroid lipids/pDNA lipoplexes inclined
      to enter H1299 cells mainly through caveolae and lipid-raft mediated endocytosis
      pathways, and an intracellular trafficking route of "lipid-raft-mediated
      endocytosis->lysosome->cell nucleic localization" was accordingly proposed. The
      study provided possible approach for developing high-performance steroid-based
      lipid gene carriers, in which the cytotoxicity, gene transfection capability,
      endocytosis pathways, and intracellular trafficking/localization manners could be
      tuned/controlled by introducing proper steroid skeletons/hydrophobes. Noteworthy,
      among the lipids, Cho-Arg showed remarkably high gene transfection efficacy, even
      under high serum concentration (50% fetal bovine serum), making it an efficient
      gene transfection agent for practical application.

PMID- 29373506
TI  - Annoyance Judgment and Measurements of Environmental Noise: A Focus on Italian
      Secondary Schools.
AB  - The effects of noise on students' health, well-being, and learning are of growing
      concern among both the general public and policy-makers in Europe. Several
      studies have highlighted the consequences of noise on children's learning and
      performance at school. This study investigates the relationship between noise
      judgment in school goers aged 11-18 and noise measurements aimed at evaluating
      their exposure at school. For this purpose, a questionnaire was administered to
      521 individuals in 28 classrooms in eight schools of four cities in Italy, with
      different environmental characteristics. Using a Likert-type scale, a selected
      set of responses related to noise generated an Annoyance Index (AI) score for
      each student and a classroom median score (MAI). From the noise data acquired, a
      global noise score (GNS) was assigned to each classroom. A higher AI was found in
      industrialized areas and among younger students. No significant differences in
      noise judgment were found by gender. A significant inverse correlation was
      described between MAI and GNS, thus the better the acoustic quality of the
      classrooms, the less the perceived noise and annoyance. The results show that
      noise perception and consequent disturbance are highly correlated with classroom
      acoustics, and confirm that annoyance represents the most widespread subjective
      response to noise.

PMID- 29373507
TI  - Effect of Cyclic Dynamic Compressive Loading on Chondrocytes and Adipose-Derived
      Stem Cells Co-Cultured in Highly Elastic Cryogel Scaffolds.
AB  - In this study, we first used gelatin/chondroitin-6-sulfate/hyaluronan/chitosan
      highly elastic cryogels, which showed total recovery from large strains during
      repeated compression cycles, as 3D scaffolds to study the effects of cyclic
      dynamic compressive loading on chondrocyte gene expression and extracellular
      matrix (ECM) production. Dynamic culture of porcine chondrocytes was studied at 1
      Hz, 10% to 40% strain and 1 to 9 h/day stimulation duration, in a mechanical
      driven multi-chamber bioreactor for 14 days. From the experimental results, we
      could identify the optimum dynamic culture condition (20% and 3 h/day) to enhance
      the chondrocytic phenotype of chondrocytes from the expression of marker (Col I,
      Col II, Col X, TNF-alpha, TGF-beta1 and IGF-1) genes by quantitative real-time
      polymerase chain reactions (qRT-PCR) and production of ECM (GAGs and Col II) by
      biochemical analysis and immunofluorescence staining. With up-regulated growth
      factor (TGF-beta1 and IGF-1) genes, co-culture of chondrocytes with porcine
      adipose-derived stem cells (ASCs) was employed to facilitate chondrogenic
      differentiation of ASCs during dynamic culture in cryogel scaffolds. By replacing
      half of the chondrocytes with ASCs during co-culture, we could obtain similar
      production of ECM (GAGs and Col II) and expression of Col II, but reduced
      expression of Col I, Col X and TNF-alpha. Subcutaneous implantation of
      cells/scaffold constructs in nude mice after mono-culture (chondrocytes or ASCs)
      or co-culture (chondrocytes + ASCs) and subject to static or dynamic culture
      condition in vitro for 14 days was tested for tissue-engineering applications.
      The constructs were retrieved 8 weeks post-implantation for histological analysis
      by Alcian blue, Safranin O and Col II immunohistochemical staining. The most
      abundant ectopic cartilage tissue was found for the chondrocytes and chondrocytes
      + ASCs groups using dynamic culture, which showed similar neo-cartilage formation
      capability with half of the chondrocytes replaced by ASCs for co-culture. This
      combined co-culture/dynamic culture strategy is expected to cut down the amount
      of donor chondrocytes needed for cartilage-tissue engineering.

PMID- 29373508
TI  - Frame-Insensitive Expression Cloning of Fluorescent Protein from Scolionema
      suvaense.
AB  - Expression cloning from cDNA is an important technique for acquiring genes
      encoding novel fluorescent proteins. However, the probability of in-frame cDNA
      insertion following the first start codon of the vector is normally only 1/3,
      which is a cause of low cloning efficiency. To overcome this issue, we developed
      a new expression plasmid vector, pRSET-TriEX, in which transcriptional slippage
      was induced by introducing a DNA sequence of (dT)14 next to the first start codon
      of pRSET. The effectiveness of frame-insensitive cloning was validated by
      inserting the gene encoding eGFP with all three possible frames to the vector.
      After transformation with one of these plasmids, E. coli cells expressed eGFP
      with no significant difference in the expression level. The pRSET-TriEX vector
      was then used for expression cloning of a novel fluorescent protein from
      Scolionema suvaense. We screened 3658 E. coli colonies transformed with pRSET
      TriEX containing Scolionema suvaense cDNA, and found one colony expressing a
      novel green fluorescent protein, ScSuFP. The highest score in protein sequence
      similarity was 42% with the chain c of multi-domain green fluorescent protein
      like protein "ember" from Anthoathecata sp. Variations in the N- and/or C
      terminal sequence of ScSuFP compared to other fluorescent proteins indicate that
      the expression cloning, rather than the sequence similarity-based methods, was
      crucial for acquiring the gene encoding ScSuFP. The absorption maximum was at 498
      nm, with an extinction efficiency of 1.17 * 105 M-1.cm-1. The emission maximum
      was at 511 nm and the fluorescence quantum yield was determined to be 0.6. Pseudo
      native gel electrophoresis showed that the protein forms obligatory homodimers.

PMID- 29373509
TI  - Offshore Earthquakes Do Not Influence Marine Mammal Stranding Risk on the
      Washington and Oregon Coasts.
AB  - The causes of marine mammals stranding on coastal beaches are not well
      understood, but may relate to topography, currents, wind, water temperature,
      disease, toxic algal blooms, and anthropogenic activity. Offshore earthquakes are
      a source of intense sound and disturbance and could be a contributing factor to
      stranding probability. We tested the hypothesis that the probability of marine
      mammal stranding events on the coasts of Washington and Oregon, USA is increased
      by the occurrence of offshore earthquakes in the nearby Cascadia subduction zone.
      The analysis carried out here indicated that earthquakes are at most, a very
      minor predictor of either single, or large (six or more animals) stranding
      events, at least for the study period and location. We also tested whether
      earthquakes inhibit stranding and again, there was no link. Although we did not
      find a substantial association of earthquakes with strandings in this study, it
      is likely that there are many factors influencing stranding of marine mammals and
      a single cause is unlikely to be responsible. Analysis of a subset of data for
      which detailed descriptions were available showed that most live stranded animals
      were pups, calves, or juveniles, and in the case of dead stranded mammals, the
      commonest cause of death was trauma, disease, and emaciation.

PMID- 29373510
TI  - Advances in Degradable Embolic Microspheres: A State of the Art Review.
AB  - Considerable efforts have been placed on the development of degradable
      microspheres for use in transarterial embolization indications. Using the
      guidance of the U.S. Food and Drug Administration (FDA) special controls document
      for the preclinical evaluation of vascular embolization devices, this review
      consolidates all relevant data pertaining to novel degradable microsphere
      technologies for bland embolization into a single reference. This review
      emphasizes intended use, chemical composition, degradative mechanisms, and pre
      clinical safety, efficacy, and performance, while summarizing the key advantages
      and disadvantages for each degradable technology that is currently under
      development for transarterial embolization. This review is intended to provide an
      inclusive reference for clinicians that may facilitate an understanding of
      clinical and technical concepts related to this field of interventional
      radiology. For materials scientists, this review highlights innovative devices
      and current evaluation methodologies (i.e., preclinical models), and is designed
      to be instructive in the development of innovative/new technologies and
      evaluation methodologies.

PMID- 29373511
TI  - Poly-N-Acetyllactosamine Neo-Glycoproteins as Nanomolar Ligands of Human Galectin
      3: Binding Kinetics and Modeling.
AB  - Galectin-3 (Gal-3) is recognized as a prognostic marker in several cancer types.
      Its involvement in tumor development and proliferation makes this lectin a
      promising target for early cancer diagnosis and anti-cancer therapies. Gal-3
      recognizes poly-N-acetyllactosamine (LacNAc)-based carbohydrate motifs of
      glycoproteins and glycolipids with a high specificity for internal LacNAc
      epitopes. This study analyzes the mode and kinetics of binding of Gal-3 to a
      series of multivalent neo-glycoproteins presenting complex poly-LacNAc-based
      oligosaccharide ligands on a scaffold of bovine serum albumin. These neo
      glycoproteins rank among the strongest Gal-3 ligands reported, with Kd reaching
      sub-nanomolar values as determined by surface plasmon resonance. Significant
      differences in the binding kinetics were observed within the ligand series,
      showing the tetrasaccharide capped with N,N'-diacetyllactosamine (LacdiNAc) as
      the strongest ligand of Gal-3 in this study. A molecular model of the Gal-3
      carbohydrate recognition domain with docked oligosaccharide ligands is presented
      that shows the relations in the binding site at the molecular level. The neo
      glycoproteins presented herein may be applied for selective recognition of Gal-3
      both on the cell surface and in blood serum.

PMID- 29373512
TI  - Self-Harm among Young People Detained in the Youth Justice System in Sri Lanka.
AB  - Self-harm is prevalent in incarcerated adults, yet comparatively few studies of
      self-harm in detained youth (and even fewer in low- and middle-income countries)
      have been published. We examined the prevalence and correlates of self-harm in a
      sample of 181 young people (mean age 15.0 years, SD = 2.3) detained in the youth
      justice system in Sri Lanka. Structured face-to-face questionnaires assessed
      demographic characteristics, family and social background, substance use, self
      harm history (including frequency, method, and intention), bullying
      victimization, physical and sexual abuse (victimization and perpetration), and
      exposure to self-harm/suicide by others. Seventy-seven participants (43%)
      reported a lifetime history of self-harm, 19 of whom (25%) who reported doing so
      with suicidal intent. Fifty participants (65% of those with a history of self
      harm) reported engaging in self-harm impulsively, with no prior planning. A
      history of self-harm was associated with being female, prior sexual abuse
      victimization, prior exposure to self-harm by friends, and a lifetime history of
      self-harm ideation. High rates of substance use, bullying victimization, parental
      incarceration, and exposure to suicide were reported across the sample. Young
      people detained in the youth justice system in Sri Lanka are a vulnerable group
      with high rates of self-harm, substance use, and psychosocial risk factors.
      Strategies for identifying and preventing self-harm, and targeted psychological
      interventions designed specifically to address impulsivity, may contribute to
      more positive outcomes in this marginalised population.

PMID- 29373513
TI  - Almond Consumption and Processing Affects the Composition of the Gastrointestinal
      Microbiota of Healthy Adult Men and Women: A Randomized Controlled Trial.
AB  - BACKGROUND: Almond processing has been shown to differentially impact
      metabolizable energy; however, the effect of food form on the gastrointestinal
      microbiota is under-investigated. OBJECTIVE: We aimed to assess the
      interrelationship of almond consumption and processing on the gastrointestinal
      microbiota. DESIGN: A controlled-feeding, randomized, five-period, crossover
      study with washouts between diet periods was conducted in healthy adults (n =
      18). Treatments included: (1) zero servings/day of almonds (control); (2) 1.5
      servings (42 g)/day of whole almonds; (3) 1.5 servings/day of whole, roasted
      almonds; (4) 1.5 servings/day of roasted, chopped almonds; and (5) 1.5
      servings/day of almond butter. Fecal samples were collected at the end of each
      three-week diet period. RESULTS: Almond consumption increased the relative
      abundances of Lachnospira, Roseburia, and Dialister (p <= 0.05). Comparisons
      between control and the four almond treatments revealed that chopped almonds
      increased Lachnospira, Roseburia, and Oscillospira compared to control (p <
      0.05), while whole almonds increased Dialister compared to control (p = 0.007).
      There were no differences between almond butter and control. CONCLUSIONS: These
      results reveal that almond consumption induced changes in the microbial community
      composition of the human gastrointestinal microbiota. Furthermore, the degree of
      almond processing (e.g., roasting, chopping, and grinding into butter)
      differentially impacted the relative abundances of bacterial genera.

PMID- 29373515
TI  - A Review of Apps for Calming, Relaxation, and Mindfulness Interventions for
      Pediatric Palliative Care Patients.
AB  - Patients and families increasingly use mobile apps as a relaxation and
      distraction intervention for children with complex, chronic medical conditions in
      the waiting room setting or during inpatient hospitalizations; and yet, there is
      limited data on app quality assessment or review of these apps for level of
      engagement, functionality, aesthetics, or applicability for palliative pediatric
      patients. The pediatric palliative care study team searched smartphone
      application platforms for apps relevant to calming, relaxation, and mindfulness
      for pediatric and adolescent patients. Apps were reviewed using a systematic data
      extraction tool. Validated Mobile Application Rating Scale (MARS) scores were
      determined by two blinded reviewers. Apps were then characterized by infant,
      child, adolescent, and adult caregiver group categories. Reviewer discussion
      resulted in consensus. Sixteen of the 22 apps identified were included in the
      final analysis. The apps operated on either iOS or Android platforms. All were
      available in English with four available in Spanish. Apps featured a relaxation
      approach (12/16), soothing images (8/16), and breathing techniques (8/16). Mood
      and sleep patterns were the main symptoms targeted by apps. Provision of mobile
      apps resource summary has the potential to foster pediatric palliative care
      providers' knowledge of app functionality and applicability as part of ongoing
      patient care.

PMID- 29373517
TI  - Prediction of Tensile Behavior of UHSFRC Considering the Flow Field in the
      Placing Dominated by Shear Flow.
AB  - Considering the case of fabricating a UHSFRC (ultra-high strength fiber
      reinforced concrete) beam with the method of one end placing and self-flowing to
      the other end, it was intended to simulate the variation of the fiber orientation
      distribution according to the flow distance and the variation of the resultant
      tensile behaviors. Then the validity of the simulation approach was shown by
      comparing the simulated results with experimental ones. A three-point bending
      test with a notched beam was adopted for the experiment and a finite element
      analysis was performed to obtain the simulated results for the bending test
      considering the flow-dependent tensile behavior of the UHSFRC. From the
      simulation for the fiber orientation distribution according to the flow distance,
      it could be found that the major change in the fiber orientation distribution
      took place within a short flow distance and most of the fibers became nearly
      aligned to the flow direction. After some flow distance, there was a not-so
      remarkable variation in the fiber orientation distribution that could influence
      the tensile behavior of the composite. For this flow region, the consistent
      flexural test results, regardless of flow distance, demonstrate the reliability
      of the simulation.

PMID- 29373514
TI  - The Ever-Evolving Concept of the Cancer Stem Cell in Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic
      cancer, is the 4th most frequent cause of cancer-related death worldwide,
      primarily due to the inherent chemoresistant nature and metastatic capacity of
      this tumor. The latter is believed to be mainly due to the existence of a
      subpopulation of highly plastic "stem"-like cells within the tumor, known as
      cancer stem cells (CSCs), which have been shown to have unique metabolic,
      autophagic, invasive, and chemoresistance properties that allow them to
      continuously self-renew and escape chemo-therapeutic elimination. As such,
      current treatments for the majority of PDAC patients are not effective and do not
      significantly impact overall patient survival (<7 months) as they do not affect
      the pancreatic CSC (PaCSC) population. In this context, it is important to
      highlight the need to better understand the characteristics of the PaCSC
      population in order to develop new therapies to target these cells. In this
      review, we will provide the latest updates and knowledge on the inherent
      characteristics of PaCSCs, particularly their unique biological properties
      including chemoresistance, epithelial to mesenchymal transition, plasticity,
      metabolism and autophagy.

PMID- 29373516
TI  - Phycoerythrin Peptide from Pyropia yezoensis Alleviates Endoplasmic Reticulum
      Stress Caused by Perfluorooctane Sulfonate-Induced Calcium Dysregulation.
AB  - Perfluorooctane sulfonate (PFOS), a stable fluorosurfactant, causes endoplasmic
      reticulum (ER) stress in the brain. This study was designed to investigate
      whether a phycoerythrin-derived peptide of Pyropia yezoensis (PYP) reduces PFOS
      induced ER stress associated with calcium dysregulation. The protective effects
      of PYP were determined by cell viability, immunoblotting for ER stress response
      protein glucose-regulated protein 78 (GRP78) and calcium-dependent protein
      kinases in rat frontal cortical neurons. PFOS-induced decrease in cell viability
      was attenuated by PYP pretreatment (1 ug/mL) for 24 h, which was downregulated by
      inhibiting tropomyosin-receptor kinase B (TrkB). PYP pretreatment downregulated
      the increase in intracellular calcium levels and phosphorylation of
      calcium/calmodulin-dependent protein kinase II and c-Jun N-terminal kinase which
      are associated with a PFOS-induced increase in GRP78. The PFOS-induced increase
      in GRP78 was downregulated via activation of TrkB receptor-linked extracellular
      signal-regulated kinases 1/2 (ERK1/2) by PYP pretreatment. Moreover, PYP
      microinjections (1 ug/kg, 0.54 nmol) attenuated the GRP78 expression in rat
      prefrontal cortex caused by PFOS (10 mg/kg) exposure for 2 weeks. These findings
      demonstrate that PYP enhances frontal cortical neuron viability via activation of
      TrkB receptor-ERK1/2 signaling and attenuation of ER stress in rat prefrontal
      cortex against PFOS exposure, suggesting that PYP might prevent neuronal
      dysfunctions caused by PFOS-induced ER stress.

PMID- 29373518
TI  - Impact of MAC Delay on AUV Localization: Underwater Localization Based on
      Hyperbolic Frequency Modulation Signal.
AB  - Medium Access Control (MAC) delay which occurs between the anchor node's
      transmissions is one of the error sources in underwater localization. In
      particular, in AUV localization, the MAC delay significantly degrades the ranging
      accuracy. The Cramer-Rao Low Bound (CRLB) definition theoretically proves that
      the MAC delay significantly degrades the localization performance. This paper
      proposes underwater localization combined with multiple access technology to
      decouple the localization performance from the MAC delay. Towards this goal, we
      adopt hyperbolic frequency modulation (HFM) signal that provides multiplexing
      based on its good property, high-temporal correlation. Owing to the multiplexing
      ability of the HFM signal, the anchor nodes can transmit packets without MAC
      delay, i.e., simultaneous transmission is possible. In addition, the simulation
      results show that the simultaneous transmission is not an optional communication
      scheme, but essential for the localization of mobile object in underwater.

PMID- 29373519
TI  - Responses of an Agricultural Soil Microbiome to Flooding with Seawater after
      Managed Coastal Realignment.
AB  - Coastal areas have become more prone to flooding with seawater due to climate
      change-induced sea-level rise and intensified storm surges. One way to cope with
      this issue is by "managed coastal realignment", where low-lying coastal areas are
      no longer protected and instead flooded with seawater. How flooding with seawater
      impacts soil microbiomes and the biogeochemical cycling of elements is poorly
      understood. To address this, we conducted a microcosm experiment using soil cores
      collected at the nature restoration project site Gyldensteen Strand (Denmark),
      which were flooded with seawater and monitored over six months. Throughout the
      experiment, biogeochemical analyses, microbial community fingerprinting and the
      quantification of marker genes documented clear shifts in microbiome composition
      and activity. The flooding with seawater initially resulted in accelerated
      heterotrophic activity that entailed high ammonium production and net removal of
      nitrogen from the system, also demonstrated by a concurrent increase in the
      abundances of marker genes for ammonium oxidation and denitrification. Due to the
      depletion of labile soil organic matter, microbial activity decreased after
      approximately four months. The event of flooding caused the largest shifts in
      microbiome composition with the availability of labile organic matter
      subsequently being the most important driver for the succession in microbiome
      composition in soils flooded with seawater.

PMID- 29373521
TI  - Detection of Abrin by Electrochemiluminescence Biosensor Based on Screen Printed
      Electrode.
AB  - For the convenience of fast measurement in the outdoor environment, a portable
      electrochemiluminescence biosensor with the screen-printed electrode as the
      reaction center was developed, which possesses the characteristics of high
      sensitivity, small scale, simplified operation and so on, and has been used for
      in situ detection of abrin. First, combining with magnetic separation technique,
      the "biotin-avidin" method was used to immobilize the polyclonal antibody (pcAb)
      on the magnetic microspheres surface as the capture probe. Secondly, the
      Ru(bpy)32+-labeled monoclonal antibody (mcAb) was used as the specific
      electrochemiluminescence signal probe. Then, the "mcAb-toxin-pcAb" sandwich model
      was built to actualize the quantitative detection of abrin on the surface of the
      screen-printed electrode. The linear detection range was 0.5-1000 ng/mL; the
      regression equation was Y = 89.251lgX + 104.978 (R = 0.9989, n = 7, p < 0.0001);
      and the limit of detection (LOD) was 0.1 ng/mL. The sensing system showed high
      sensitivity, excellent specificity and good anti-interference ability, and could
      be used for the analysis of trace abrin in various environmental samples with
      good recovery and reproducibility. Compared with the traditional
      electrochemiluminescence sensing device, its miniaturization and portability
      gives it potential to satisfy the requirement of in situ detection.

PMID- 29373520
TI  - Complete Chloroplast Genome Sequence and Phylogenetic Analysis of Paeonia ostii.
AB  - Paeonia ostii, a common oil-tree peony, is important ornamentally and
      medicinally. However, there are few studies on the chloroplast genome of Paeonia
      ostii. We sequenced and analyzed the complete chloroplast genome of P. ostii. The
      size of the P. ostii chloroplast genome is 152,153 bp, including a large single
      copy region (85,373 bp), a small single-copy region (17,054 bp), and a pair of
      inverted repeats regions (24,863 bp). The P. ostii chloroplast genome encodes 111
      genes, including 77 protein-coding genes, four ribosomal RNA genes, and 30
      transfer RNA genes. The genome contains forward repeats (22), palindromic repeats
      (28), and tandem repeats (24). The presence of rich simple-sequence repeat loci
      in the genome provides opportunities for future population genetics work for
      breeding new varieties. A phylogenetic analysis showed that P. ostii is more
      closely related to Paeonia delavayi and Paeonialudlowii than to Paeoniaobovata
      and Paeoniaveitchii. The results of this study provide an assembly of the whole
      chloroplast genome of P. ostii, which may be useful for future breeding and
      further biological discoveries. It will provide a theoretical basis for the
      improvement of peony yield and the determination of phylogenetic status.

PMID- 29373522
TI  - lncRNA Gene Signatures for Prediction of Breast Cancer Intrinsic Subtypes and
      Prognosis.
AB  - Background: Breast cancer is intrinsically heterogeneous and is commonly
      classified into four main subtypes associated with distinct biological features
      and clinical outcomes. However, currently available data resources and methods
      are limited in identifying molecular subtyping on protein-coding genes, and
      little is known about the roles of long non-coding RNAs (lncRNAs), which occupies
      98% of the whole genome. lncRNAs may also play important roles in subgrouping
      cancer patients and are associated with clinical phenotypes. Methods: The purpose
      of this project was to identify lncRNA gene signatures that are associated with
      breast cancer subtypes and clinical outcomes. We identified lncRNA gene
      signatures from The Cancer Genome Atlas (TCGA )RNAseq data that are associated
      with breast cancer subtypes by an optimized 1-Norm SVM feature selection
      algorithm. We evaluated the prognostic performance of these gene signatures with
      a semi-supervised principal component (superPC) method. Results: Although lncRNAs
      can independently predict breast cancer subtypes with satisfactory accuracy, a
      combined gene signature including both coding and non-coding genes will give the
      best clinically relevant prediction performance. We highlighted eight potential
      biomarkers (three from coding genes and five from non-coding genes) that are
      significantly associated with survival outcomes. Conclusion: Our proposed methods
      are a novel means of identifying subtype-specific coding and non-coding potential
      biomarkers that are both clinically relevant and biologically significant.

PMID- 29373523
TI  - Evolution of Structural and Optical Properties of ZnO Nanorods Grown on Vacuum
      Annealed Seed Crystallites.
AB  - In this study, the ambient condition for the as-coated seed layer (SL) annealing
      at 350  degrees C is varied from air or nitrogen to vacuum to examine the
      evolution of structural and optical properties of ZnO nanorods (NRs). The NR
      crystals of high surface density (~240 rods/MUm2) and aspect ratio (~20.3) show
      greatly enhanced (002) degree of orientation and crystalline quality, when grown
      on the SLs annealed in vacuum, compared to those annealed in air or nitrogen
      ambient. This is due to the vacuum-annealed SL crystals of a highly preferred
      orientation toward (002) and large grain sizes. X-ray photoelectron spectroscopy
      also reveals that the highest O/Zn atomic ratio of 0.89 is obtained in the case
      of vacuum-annealed SL crystals, which is due to the effective desorption of
      hydroxyl groups and other contaminants adsorbed on the surface formed during
      aqueous solution-based growth process. Near band edge emission (ultra violet
      range of 360-400 nm) of the vacuum-annealed SLs is also enhanced by 44% and 33%
      as compared to those annealed in air and nitrogen ambient, respectively, in
      photoluminescence with significant suppression of visible light emission
      associated with deep level transition. Due to this improvement of SL optical
      crystalline quality, the NR crystals grown on the vacuum-annealed SLs produce ~3
      times higher ultra violet emission intensity than the other samples. In summary,
      it is shown that the ZnO NRs preferentially grow along the wurtzite c-axis
      direction, thereby producing the high crystalline quality of nanostructures when
      they grow on the vacuum-annealed SLs of high crystalline quality with minimized
      impurities and excellent preferred orientation. The ZnO nanostructures of high
      crystalline quality achieved in this study can be utilized for a wide range of
      potential device applications such as laser diodes, light-emitting diodes,
      piezoelectric transducers and generators, gas sensors, and ultraviolet detectors.

PMID- 29373524
TI  - Photo-Induced Room-Temperature Gas Sensing with a-IGZO Based Thin-Film
      Transistors Fabricated on Flexible Plastic Foil.
AB  - We present a gas sensitive thin-film transistor (TFT) based on an amorphous
      Indium-Gallium-Zinc-Oxide (a-IGZO) semiconductor as the sensing layer, which is
      fabricated on a free-standing flexible polyimide foil. The photo-induced sensor
      response to NO2 gas at room temperature and the cross-sensitivity to humidity are
      investigated. We combine the advantages of a transistor based sensor with
      flexible electronics technology to demonstrate the first flexible a-IGZO based
      gas sensitive TFT. Since flexible plastic substrates prohibit the use of high
      operating temperatures, the charge generation is promoted with the help of UV
      light absorption, which ultimately triggers the reversible chemical reaction with
      the trace gas. Furthermore, the device fabrication process flow can be directly
      implemented in standard TFT technology, allowing for the parallel integration of
      the sensor and analog or logical circuits.

PMID- 29373525
TI  - Three-Dimensionally Hierarchical Graphene Based Aerogel Encapsulated Sulfur as
      Cathode for Lithium/Sulfur Batteries.
AB  - A simple and effective method was developed to obtain the electrode for
      lithium/sulfur (Li/S) batteries with high specific capacity and cycling
      durability via adopting an interconnected sulfur/activated carbon/graphene
      (reduced graphene oxide) aerogel (S/AC/GA) cathode architecture. The AC/GA
      composite with a well-defined interconnected conductive network was prepared by a
      reduction-induced self-assembly process, which allows for obtaining compact and
      porous structures. During this process, reduced graphene oxide (RGO) was formed,
      and due to the presence of oxygen-containing functional groups on its surface, it
      not only improves the electronic conductivity of the cathode but also effectively
      inhibits the polysulfides dissolution and shuttle. The introduced activated
      carbon allowed for lateral and vertical connection between individual graphene
      sheets, completing the formation of a stable three-dimensionally (3D)
      interconnected graphene framework. Moreover, a high specific surface area and 3D
      interconnected porous structure efficiently hosts a higher amount of active
      sulfur material, about 65 wt %. The designed S/AC/GA composite electrodes deliver
      an initial capacity of 1159 mAh g-1 at 0.1 C and can retain a capacity of 765 mAh
      g-1 after 100 cycles in potential range from 1 V to 3 V.

PMID- 29373526
TI  - The Dynamic Effects of Isosteviol on Insulin Secretion and Its Inability to
      Counteract the Impaired beta-Cell Function during Gluco-, Lipo-, and
      Aminoacidotoxicity: Studies In Vitro.
AB  - Isosteviol (ISV), a diterpene molecule, is an isomer of the backbone structure of
      a group of substances with proven antidiabetic capabilities. The aim of this
      study was to investigate if ISV elicits dynamic insulin release from pancreatic
      islets and concomitantly is able to ameliorate gluco-, lipo-, and
      aminoacidotoxicity in clonal beta-cell line (INS-1E) in relation to cell
      viability and insulin secretion. Isolated mice islets placed into perifusion
      chambers were perifused with 3.3 mM and 16.7 mM glucose with/without 10-7 M ISV.
      INS-1E cells were incubated for 72 h with either 30 mM glucose, 1 mM palmitate or
      10 mM leucine with or without 10-7 M ISV. Cell viability was evaluated with a
      Cytotoxic Fluoro-test and insulin secretion was measured in Krebs-Ringer Buffer
      at 3.3 mM and 16.7 mM glucose. In the presence of 3.3 mM glucose, 10-7 M ISV did
      not change basal insulin secretion from perifused islets. However, at a high
      glucose level of 16.7 mM, 10-7 M ISV elicited a 2.5-fold increase (-ISV: 109.92
      +/- 18.64 ng/mL vs. +ISV: 280.15 +/- 34.97 ng/mL; p < 0.01). After 72 h gluco-,
      lipo-, or aminoacidotoxicity in INS-1E cells, ISV treatment did not significantly
      affect cell viability (glucotoxicity, -ISV: 19.23 +/- 0.83%, +ISV: 18.41 +/-
      0.90%; lipotoxicity, -ISV: 70.46 +/- 3.15%, +ISV: 65.38 +/- 2.81%;
      aminoacidotoxicity: -ISV: 8.12 +/- 0.63%; +ISV: 7.75 +/- 0.38%, all
      nonsignificant). ISV did not improve impaired insulin secretion (glucotoxicity, 
      ISV: 52.22 +/- 2.90 ng/mL, +ISV: 47.24 +/- 3.61 ng/mL; lipotoxicity, -ISV: 19.94
      +/- 4.10 ng/mL, +ISV: 22.12 +/- 3.94 ng/mL; aminoacidotoxicity: -ISV: 32.13 +/-
      1.00 ng/mL; +ISV: 30.61 +/- 1.54 ng/mL, all nonsignificant). In conclusion, ISV
      acutely stimulates insulin secretion at high but not at low glucose
      concentrations. However, ISV did not counteract cell viability or cell
      dysfunction during gluco-, lipo-, or aminoacidotoxicity in INS-1E cells.

PMID- 29373527
TI  - Transcriptome Analysis of Kiwifruit in Response to Pseudomonas syringae pv.
      actinidiae Infection.
AB  - Kiwifruit bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa)
      has brought about a severe threat to the kiwifruit industry worldwide since its
      first outbreak in 2008. Studies on other pathovars of P. syringae are revealing
      the pathogenesis of these pathogens, but little about the mechanism of kiwifruit
      bacterial canker is known. In order to explore the species-specific interaction
      between Psa and kiwifruit, we analyzed the transcriptomic profile of kiwifruit
      infected by Psa. After 48 h, 8255 differentially expressed genes were identified,
      including those involved in metabolic process, secondary metabolites metabolism
      and plant response to stress. Genes related to biosynthesis of terpens were
      obviously regulated, indicating terpens may play roles in suppressing the growth
      of Psa. We identified 283 differentially expressed resistant genes, of which most
      U-box domain containing genes were obviously up regulated. Expression of genes
      involved in plant immunity was detected and some key genes showed differential
      expression. Our results suggest that Psa induced defense response of kiwifruit,
      including PAMP (pathogen/microbe-associated molecular patterns)-triggered
      immunity, effector-triggered immunity and hypersensitive response. Metabolic
      process was adjusted to adapt to these responses and production of secondary
      metabolites may be altered to suppress the growth of Psa.

PMID- 29373528
TI  - A IR-Femtosecond Laser Hybrid Sensor to Measure the Thermal Expansion and Thermo
      Optical Coefficient of Silica-Based FBG at High Temperatures.
AB  - In this paper, a hybrid sensor was fabricated using a IR-femtosecond laser to
      measure the thermal expansion and thermo-optical coefficient of silica-based
      fiber Bragg gratings (FBGs). The hybrid sensor was composed of an inline fiber
      Fabry-Perot interferometer (FFPI) cavity and a type-II FBG. Experiment results
      showed that the type-II FBG had three high reflectivity resonances in the
      wavelength ranging from 1100 to 1600 nm, showing the peaks in 1.1, 1.3 and 1.5
      MUm, respectively. The thermal expansion and thermo-optical coefficient (1.3 MUm,
      1.5 MUm) of silica-based FBG, under temperatures ranging from 30 to 1100  degrees
      C, had been simultaneously calculated by measuring the wavelength of the type-II
      FBG and FFPI cavity length.

PMID- 29373529
TI  - A Systematic Review of Behavioural Interventions Promoting Healthy Eating among
      Older People.
AB  - Because eating habits are inseparably linked with people's physical health,
      effective behaviour interventions are highly demanded to promote healthy eating
      among older people. The aim of this systematic review was to identify effective
      diet interventions for older people and provide useful evidence and direction for
      further research. Three electronic bibliographic databases-PubMed, Scopus and Web
      of Science Core Collection were used to conduct a systematic literature search
      based on fixed inclusion and exclusion criteria. English language peer-reviewed
      journal articles published between 2011 and 2016 were selected for data
      extraction and quality assessment. Finally, a total of 16 studies were
      identified. The studies' duration ranged from three weeks to seven years. The
      majority of studies were carried out in European countries. Seven studies had a
      moderate quality while the remaining studies were at a less than moderate level.
      Three dietary educational interventions and all meal service related
      interventions reported improvements in older people's dietary variety, nutrition
      status, or other health-related eating behaviours. Multicomponent dietary
      interventions mainly contributed to the reduction of risk of chronic disease. The
      results supported that older people could achieve a better dietary quality if
      they make diet-related changes by receiving either dietary education or healthier
      meal service. Further high-quality studies are required to promote healthy eating
      among older people by taking regional diet patterns, advanced information
      technology, and nudging strategies into account.

PMID- 29373530
TI  - Type-4 Resistant Starch in Substitution for Available Carbohydrate Reduces
      Postprandial Glycemic Response and Hunger in Acute, Randomized, Double-Blind,
      Controlled Study.
AB  - Resistant starch (RS) is a type of dietary fiber that has been acknowledged for
      multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory
      of RS that has been more intensively studied as new types of RS4 emerge in the
      food supply. The primary aim of this randomized, double-blind, controlled study
      was to characterize the postprandial glucose response in healthy adults after
      consuming a high fiber scone containing a novel RS4 or a low fiber control scone
      without RS4. Secondary aims included assessment of postprandial insulin response,
      postprandial satiety, and gastrointestinal tolerance. The fiber scone
      significantly reduced postprandial glucose and insulin incremental areas under
      the curves (43-45% reduction, 35-40% reduction, respectively) and postprandial
      glucose and insulin maximum concentrations (8-10% and 22% reduction,
      respectively). The fiber scone significantly reduced hunger and desire to eat
      during the 180 min following consumption and yielded no gastrointestinal side
      effects compared with the control scone. The results from this study demonstrate
      that a ready-to-eat baked-good, such as a scone, can be formulated with RS4
      replacing refined wheat flour to yield statistically significant and clinically
      meaningful reductions in blood glucose and insulin excursions. This is the first
      study to report increased satiety after short-term RS4 intake, which warrants
      further investigation in long-term feeding studies.

PMID- 29373531
TI  - Comparative Studies on Thermal, Mechanical, and Flame Retardant Properties of PBT
      Nanocomposites via Different Oxidation State Phosphorus-Containing Agents
      Modified Amino-CNTs.
AB  - High-performance poly(1,4-butylene terephthalate) (PBT) nanocomposites have been
      developed via the consideration of phosphorus-containing agents and amino-carbon
      nanotube (A-CNT). One-pot functionalization method has been adopted to prepare
      functionalized CNTs via the reaction between A-CNT and different oxidation state
      phosphorus-containing agents, including chlorodiphenylphosphine (DPP-Cl),
      diphenylphosphinic chloride (DPP(O)-Cl), and diphenyl phosphoryl chloride
      (DPP(O3)-Cl). These functionalized CNTs, DPP(Ox)-A-CNTs (x = 0, 1, 3), were,
      respectively, mixed with PBT to obtain the CNT-based polymer nanocomposites
      through a melt blending method. Scanning electron microscope observations
      demonstrated that DPP(Ox)-A-CNT nanoadditives were homogeneously distributed
      within PBT matrix compared to A-CNT. The incorporation of DPP(Ox)-A-CNT improved
      the thermal stability of PBT. Moreover, PBT/DPP(O3)-A-CNT showed the highest
      crystallization temperature and tensile strength, due to the superior dispersion
      and interfacial interactions between DPP(O3)-A-CNT and PBT. PBT/DPP(O)-A-CNT
      exhibited the best flame retardancy resulting from the excellent carbonization
      effect. The radicals generated from decomposed polymer were effectively trapped
      by DPP(O)-A-CNT, leading to the reduction of heat release rate, smoke production
      rate, carbon dioxide and carbon monoxide release during cone calorimeter tests.

PMID- 29373532
TI  - The Role of Bacteria, Probiotics and Diet in Irritable Bowel Syndrome.
AB  - Irritable bowel syndrome is a highly prevalent gastrointestinal disorder that
      threatens the quality of life of millions and poses a substantial financial
      burden on healthcare systems around the world. Intense research into the human
      microbiome has led to fascinating discoveries which directly and indirectly
      implicate the diversity and function of this occult organ in irritable bowel
      syndrome (IBS) pathophysiology. The benefit of manipulating the gastrointestinal
      microbiota with diet and probiotics to improve symptoms has been demonstrated in
      a wealth of both animal and human studies. The positive and negative mechanistic
      roles bacteria play in IBS will be explored and practical probiotic and dietary
      choices offered.

PMID- 29373533
TI  - Suppression of Fatty Acid and Triglyceride Synthesis by the Flavonoid Orientin
      through Decrease of C/EBPdelta Expression and Inhibition of PI3K/Akt-FOXO1
      Signaling in Adipocytes.
AB  - Plant flavonoids have a variety of biological properties. In a previous study, we
      found that the tea of the Asian dayflower, Commelina communis L., decreased the
      body weight gain in high-fat diet-fed mice. In this study, we studied the anti
      adipogenic ability of a flavonoid orientin that is found in abundance in C.
      communis. Orientin repressed the accumulation of intracellular triglyceride (TG)
      in mouse adipocyte 3T3-L1 cells. The treatment with orientin also decreased the
      mRNA levels of the genes involved in adipogenesis, lipogenesis, lipolysis, and TG
      synthesis, and reduced the release of glycerol. Orientin lowered the expression
      of CCAAT/enhancer binding protein (C/EBP) delta in the early stage of
      adipogenesis, leading to a decrease in the expression of the adipogenic master
      transcription factors such as peroxisome proliferator-activated receptor (PPAR)
      gamma and C/EBPalpha. Moreover, the anti-adipogenic effect of orientin repressed
      the phosphorylation of Akt and subsequent phosphorylation of forkhead box protein
      O1 (FOXO1), which inhibits the transcription of the Ppar gene. These results
      indicate that a plant flavonoid orientin suppressed the expression of the
      Ppargamma gene through repression of C/ebpdelta expression and inhibition of the
      phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes.

PMID- 29373535
TI  - Strapdown Airborne Gravimetry Quality Assessment Method Based on Single Survey
      Line Data: A Study by SGA-WZ02 Gravimeter.
AB  - Quality assessment is an important part in the strapdown airborne gravimetry.
      Root mean square error (RMSE) evaluation method is a classical way to evaluate
      the gravimetry quality, but classical evaluation methods are preconditioned by
      extra flight or reference data. Thus, a method, which is able to largely conquer
      the premises of classical quality assessment methods and can be used in single
      survey line, has been developed in this paper. According to theoretical analysis,
      the method chooses the stability of two horizontal attitude angles, horizontal
      specific force and vertical specific force as the determinants of quality
      assessment method. The actual data, collected by SGA-WZ02 from 13 flights 21
      lines in certain survey, was used to build the model and elaborate the method. To
      substantiate the performance of the quality assessment model, the model is
      applied in extra repeat line flights from two surveys. Compared with internal
      RMSE, standard deviation of assessment residuals are 0.23 mGal and 0.16 mGal in
      two surveys, which shows that the quality assessment method is reliable and
      stricter. The extra flights are not necessary by specially arranging the route of
      flights. The method, summarized from SGA-WZ02, is a feasible approach to assess
      gravimetry quality using single line data and is also suitable for other
      strapdown gravimeters.

PMID- 29373534
TI  - Betaine Supplementation Enhances Lipid Metabolism and Improves Insulin Resistance
      in Mice Fed a High-Fat Diet.
AB  - Obesity is a major driver of metabolic diseases such as nonalcoholic fatty liver
      disease, certain cancers, and insulin resistance. However, there are no effective
      drugs to treat obesity. Betaine is a nontoxic, chemically stable and naturally
      occurring molecule. This study shows that dietary betaine supplementation
      significantly inhibits the white fat production in a high-fat diet (HFD)-induced
      obese mice. This might be due to betaine preventing the formation of new white
      fat (WAT), and guiding the original WAT to burn through stimulated mitochondrial
      biogenesis and promoting browning of WAT. Furthermore, dietary betaine
      supplementation decreases intramyocellular lipid accumulation in HFD-induced
      obese mice. Further analysis shows that betaine supplementation reduced
      intramyocellular lipid accumulation might be associated with increasing
      polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of
      fatty acid synthesis in muscle. Notably, by performing insulin-tolerance tests
      (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could
      be observed for improvement of obesity and non-obesity induced insulin
      resistance. Together, these findings could suggest that inhibiting WAT
      production, intramyocellular lipid accumulation and inflammation, betaine
      supplementation limits HFD-induced obesity and improves insulin resistance.

PMID- 29373536
TI  - Sustainability of a Compartmentalized Host-Parasite Replicator System under
      Periodic Washout-Mixing Cycles.
AB  - The emergence and dominance of parasitic replicators are among the major hurdles
      for the proliferation of primitive replicators. Compartmentalization of
      replicators is proposed to relieve the parasite dominance; however, it remains
      unclear under what conditions simple compartmentalization uncoupled with internal
      reaction secures the long-term survival of a population of primitive replicators
      against incessant parasite emergence. Here, we investigate the sustainability of
      a compartmentalized host-parasite replicator (CHPR) system undergoing periodic
      washout-mixing cycles, by constructing a mathematical model and performing
      extensive simulations. We describe sustainable landscapes of the CHPR system in
      the parameter space and elucidate the mechanism of phase transitions between
      sustainable and extinct regions. Our findings revealed that a large population
      size of compartments, a high mixing intensity, and a modest amount of nutrients
      are important factors for the robust survival of replicators. We also found two
      distinctive sustainable phases with different mixing intensities. These results
      suggest that a population of simple host-parasite replicators assumed before the
      origin of life can be sustained by a simple compartmentalization with periodic
      washout-mixing processes.

PMID- 29373537
TI  - Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with
      Caffeine: A Preclinical Study in Arthritic Rats.
AB  - The purpose of the present study was to determine whether caffeine modifies the
      pharmacokinetics and pharmacodynamics of (S)-ketoprofen following oral
      administration in a gout-type pain model. 3.2 mg/kg of (S)-ketoprofen alone and
      combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma
      levels were determined between 0.5 and 24.0 h. Additionally, antinociception was
      evaluated based on the protocol of the PIFIR (pain-induced functional impairment
      in the rat) model before blood sampling between 0.5 and 4.0 h. Significant
      differences in Cmax, AUC0-24, and AUC0-infinity values were observed with
      caffeine administration (p < 0.05). Also, significant differences in Emax, Tmax,
      and AUC0-4 values were determined when comparing the treatments with and without
      caffeine (p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a
      counter-clockwise hysteresis loop was observed regardless of the administration
      of caffeine. When the relationship between AUCe and AUCp was fitted to the
      sigmoidal Emax model, a satisfactory correlation was found (R2 > 0.99) as well as
      significant differences in Emax and EC50 values (p < 0.05). With caffeine, Emax
      and EC50 values changed by 489.5% and 695.4%, respectively. The combination
      studied represents a convenient alternative for the treatment of pain when
      considering the advantages offered by using drugs with different mechanisms of
      action.

PMID- 29373538
TI  - Novel Formulations of Phase Change Materials-Epoxy Composites for Thermal Energy
      Storage.
AB  - This research aimed to evaluate the thermal properties of new formulations of
      phase change materials (PCMs)-epoxy composites, containing a thickening agent and
      a thermally conductive phase. The composite specimens produced consisted of
      composites fabricated using (a) inorganic PCMs (hydrated salts), epoxy resins and
      aluminum particulates or (b) organic PCM (paraffin), epoxy resins, and copper
      particles. Differential Scanning Calorimetry (DSC) was used to analyze the
      thermal behavior of the samples, while hardness measurements were used to
      determine changes in mechanical properties at diverse PCM and conductive phase
      loading values. The results indicate that the epoxy matrix can act as a container
      for the PCM phase without hindering the heat-absorbing behavior of the PCMs
      employed. Organic PCMs presented reversible phase transformations over multiple
      cycles, an advantage that was lacking in their inorganic counterparts. The
      enthalpy of the organic PCM-epoxy specimens increased linearly with the PCM
      content in the matrix. The use of thickening agents prevented phase segregation
      issues and allowed the fabrication of specimens containing up to 40% PCM, a
      loading significantly higher than others reported. The conductive phase seemed to
      improve the heat transfer and the mechanical properties of the composites when
      present in low percentages (<10 wt %); however, given its mass, the enthalpy
      detected in the composites was reduced as their loading further increased. The
      conductive phase combination (PCM + epoxy resin + hardener + thickening agent)
      presents great potential as a heat-absorbing material at the temperatures
      employed.

PMID- 29373540
TI  - Functionalizable Sol-Gel Silica Coatings for Corrosion Mitigation.
AB  - Corrosion is constantly a major problem of the world economy in the field of
      metal products, metal processing and other areas that utilise metals. Previously
      used compounds utilizing hexavalent chromium were amongst the most effective
      materials for corrosion protection but regulations have been recently introduced
      that forbid their use. Consequently, there is a huge drive by engineers,
      technologists and scientists from different disciplines focused on searching a
      new, more effective and environmentally-friendly means of corrosion protection.
      One novel group of materials with the potential to solve metal protection
      problems are sol-gel thin films, which are increasingly interesting as mitigation
      corrosion barriers. These environmentally-friendly and easy-to-obtain coatings
      have the promise to be an effective alternative to hexavalent chromium compounds
      using for anti-corrosion industrial coatings. In this review the authors present
      a range of different solutions for slow down the corrosion processes of metallic
      substrates by using the oxides and doped oxides obtained by the sol-gel method.
      Examples of techniques used to the sol-gel coating examinations, in terms of anti
      corrosion protection, are also presented.

PMID- 29373539
TI  - Acute Limb Ischemia-Much More Than Just a Lack of Oxygen.
AB  - Acute ischemia of an extremity occurs in several stages, a lack of oxygen being
      the primary contributor of the event. Although underlying patho-mechanisms are
      similar, it is important to determine whether it is an acute or chronic event.
      Healthy tissue does not contain enlarged collaterals, which are formed in
      chronically malperfused tissue and can maintain a minimum supply despite
      occlusion. The underlying processes for enhanced collateral blood flow are
      sprouting vessels from pre-existing vessels (via angiogenesis) and a lumen
      extension of arterioles (via arteriogenesis). While disturbed flow patterns with
      associated local low shear stress upregulate angiogenesis promoting genes,
      elevated shear stress may trigger arteriogenesis due to increased blood volume.
      In case of an acute ischemia, especially during the reperfusion phase, fluid
      transfer occurs into the tissue while the vascular bed is simultaneously reduced
      and no longer reacts to vaso-relaxing factors such as nitric oxide. This process
      results in an exacerbative cycle, in which increased peripheral resistance leads
      to an additional lack of oxygen. This whole process is accompanied by an
      inundation of inflammatory cells, which amplify the inflammatory response by
      cytokine release. However, an extremity is an individual-specific composition of
      different tissues, so these processes may vary dramatically between patients. The
      image is more uniform when broken down to the single cell stage. Because each
      cell is dependent on energy produced from aerobic respiration, an event of acute
      hypoxia can be a life-threatening situation. Aerobic processes responsible for
      yielding adenosine triphosphate (ATP), such as the electron transport chain and
      oxidative phosphorylation in the mitochondria, suffer first, thus disrupting the
      integrity of cellular respiration. One consequence of this is irreparable damage
      of the cell membrane due to an imbalance of electrolytes. The eventual increase
      in net fluid influx associated with a decrease in intracellular pH is considered
      an end-stage event. Due to the lack of ATP, individual cell organelles can no
      longer sustain their activity, thus initiating the cascade pathways of apoptosis
      via the release of cytokines such as the BCL2 associated X protein (BAX). As
      ischemia may lead to direct necrosis, inflammatory processes are further
      aggravated. In the case of reperfusion, the flow of nascent oxygen will cause
      additional damage to the cell, further initiating apoptosis in additional
      surrounding cells. In particular, free oxygen radicals are formed, causing severe
      damage to cell membranes and desoxyribonucleic acid (DNA). However, the increased
      tissue stress caused by this process may be transient, as radical scavengers may
      attenuate the damage. Taking the above into final consideration, it is clearly
      elucidated that acute ischemia and subsequent reperfusion is a process that leads
      to acute tissue damage combined with end-organ loss of function, a condition that
      is difficult to counteract.

PMID- 29373541
TI  - Effect of Cation Ordering on the Performance and Chemical Stability of Layered
      Double Perovskite Cathodes.
AB  - The effect of A-site cation ordering on the cathode performance and chemical
      stability of A-site cation ordered LaBaCo2O5+delta and disordered La0.5Ba0.5CoO3
      delta materials are reported. Symmetric half-cells with a proton-conducting
      BaZr0.9Y0.1O3-delta electrolyte were prepared by ceramic processing, and good
      chemical compatibility of the materials was demonstrated. Both A-site ordered
      LaBaCo2O5+delta and A-site disordered La0.5Ba0.5CoO3-delta yield excellent
      cathode performance with Area Specific Resistances as low as 7.4 and 11.5
      Omega.cm2 at 400  degrees C and 0.16 and 0.32 Omega.cm2 at 600  degrees C in 3%
      humidified synthetic air respectively. The oxygen vacancy concentration,
      electrical conductivity, basicity of cations and crystal structure were evaluated
      to rationalize the electrochemical performance of the two materials. The
      combination of high-basicity elements and high electrical conductivity as well as
      sufficient oxygen vacancy concentration explains the excellent performance of
      both LaBaCo2O5+delta and La0.5Ba0.5CoO3-delta materials at high temperatures. At
      lower temperatures, oxygen-deficiency in both materials is greatly reduced,
      leading to decreased performance despite the high basicity and electrical
      conductivity. A-site cation ordering leads to a higher oxygen vacancy
      concentration, which explains the better performance of LaBaCo2O5+delta. Finally,
      the more pronounced oxygen deficiency of the cation ordered polymorph and the
      lower chemical stability at reducing conditions were confirmed by coulometric
      titration.

PMID- 29373542
TI  - Environment vs. Plant Ontogeny: Arthropod Herbivory Patterns on European Beech
      Leaves along the Vertical Gradient of Temperate Forests in Central Germany.
AB  - Environmental and leaf trait effects on herbivory are supposed to vary among
      different feeding guilds. Herbivores also show variability in their preferences
      for plant ontogenetic stages. Along the vertical forest gradient, environmental
      conditions change, and trees represent juvenile and adult individuals in the
      understorey and canopy, respectively. This study was conducted in ten forests
      sites in Central Germany for the enrichment of canopy research in temperate
      forests. Arthropod herbivory of different feeding traces was surveyed on leaves
      of Fagus sylvatica Linnaeus (European beech; Fagaceae) in three strata. Effects
      of microclimate, leaf traits, and plant ontogenetic stage were analyzed as
      determining parameters for herbivory. The highest herbivory was caused by
      exophagous feeding traces. Herbivore attack levels varied along the vertical
      forest gradient for most feeding traces with distinct patterns. If differences of
      herbivory levels were present, they only occurred between juvenile and adult F.
      sylvatica individuals, but not between the lower and upper canopy. In contrast,
      differences of microclimate and important leaf traits were present between the
      lower and upper canopy. In conclusion, the plant ontogenetic stage had a stronger
      effect on herbivory than microclimate or leaf traits along the vertical forest
      gradient.

PMID- 29373544
TI  - Artificial Vector Calibration Method for Differencing Magnetic Gradient Tensor
      Systems.
AB  - The measurement error of the differencing (i.e., using two homogenous field
      sensors at a known baseline distance) magnetic gradient tensor system includes
      the biases, scale factors, nonorthogonality of the single magnetic sensor, and
      the misalignment error between the sensor arrays, all of which can severely
      affect the measurement accuracy. In this paper, we propose a low-cost artificial
      vector calibration method for the tensor system. Firstly, the error parameter
      linear equations are constructed based on the single-sensor's system error model
      to obtain the artificial ideal vector output of the platform, with the total
      magnetic intensity (TMI) scalar as a reference by two nonlinear conversions,
      without any mathematical simplification. Secondly, the Levenberg-Marquardt
      algorithm is used to compute the integrated model of the 12 error parameters by
      nonlinear least-squares fitting method with the artificial vector output as a
      reference, and a total of 48 parameters of the system is estimated
      simultaneously. The calibrated system outputs along the reference platform
      orthogonal coordinate system. The analysis results show that the artificial
      vector calibrated output can track the orientation fluctuations of TMI
      accurately, effectively avoiding the "overcalibration" problem. The accuracy of
      the error parameters' estimation in the simulation is close to 100%. The
      experimental root-mean-square error (RMSE) of the TMI and tensor components is
      less than 3 nT and 20 nT/m, respectively, and the estimation of the parameters is
      highly robust.

PMID- 29373543
TI  - Vitamin E as an Antioxidant in Female Reproductive Health.
AB  - Vitamin E was first discovered in 1922 as a substance necessary for reproduction.
      Following this discovery, vitamin E was extensively studied, and it has become
      widely known as a powerful lipid-soluble antioxidant. There has been increasing
      interest in the role of vitamin E as an antioxidant, as it has been discovered to
      lower body cholesterol levels and act as an anticancer agent. Numerous studies
      have reported that vitamin E exhibits anti-proliferative, anti-survival, pro
      apoptotic, and anti-angiogenic effects in cancer, as well as anti-inflammatory
      activities. There are various reports on the benefits of vitamin E on health in
      general. However, despite it being initially discovered as a vitamin necessary
      for reproduction, to date, studies relating to its effects in this area are
      lacking. Hence, this paper was written with the intention of providing a review
      of the known roles of vitamin E as an antioxidant in female reproductive health.

PMID- 29373546
TI  - A Micro-Resonant Gas Sensor with Nanometer Clearance between the Pole Plates.
AB  - In micro-resonant gas sensors, the capacitive detection is widely used because of
      its simple structure. However, its shortcoming is a weak signal output caused by
      a small capacitance change. Here, we reduced the initial clearance between the
      pole plates to the nanometer level, and increased the capacitance between the
      pole plates and its change during resonator vibration. We propose a fabricating
      process of the micro-resonant gas sensor by which the initial clearance between
      the pole plates is reduced to the nanometer level and a micro-resonant gas sensor
      with 200 nm initial clearance is fabricated. With this sensor, the resonant
      frequency shifts were measured when they were exposed to several different
      vapors, and high detection accuracies were obtained. The detection accuracy with
      respect to ethanol vapor was 0.4 ppm per Hz shift, and the detection accuracy
      with respect to hydrogen and ammonias vapors was 3 ppm and 0.5 ppm per Hz shift,
      respectively.

PMID- 29373548
TI  - Hyperspectral Image Classification for Land Cover Based on an Improved Interval
      Type-II Fuzzy C-Means Approach.
AB  - Few studies have examined hyperspectral remote-sensing image classification with
      type-II fuzzy sets. This paper addresses image classification based on a
      hyperspectral remote-sensing technique using an improved interval type-II fuzzy c
      means (IT2FCM*) approach. In this study, in contrast to other traditional fuzzy c
      means-based approaches, the IT2FCM* algorithm considers the ranking of interval
      numbers and the spectral uncertainty. The classification results based on a
      hyperspectral dataset using the FCM, IT2FCM, and the proposed improved IT2FCM*
      algorithms show that the IT2FCM* method plays the best performance according to
      the clustering accuracy. In this paper, in order to validate and demonstrate the
      separability of the IT2FCM*, four type-I fuzzy validity indexes are employed, and
      a comparative analysis of these fuzzy validity indexes also applied in FCM and
      IT2FCM methods are made. These four indexes are also applied into different
      spatial and spectral resolution datasets to analyze the effects of spectral and
      spatial scaling factors on the separability of FCM, IT2FCM, and IT2FCM* methods.
      The results of these validity indexes from the hyperspectral datasets show that
      the improved IT2FCM* algorithm have the best values among these three algorithms
      in general. The results demonstrate that the IT2FCM* exhibits good performance in
      hyperspectral remote-sensing image classification because of its ability to
      handle hyperspectral uncertainty.

PMID- 29373549
TI  - A Novel Grid SINS/DVL Integrated Navigation Algorithm for Marine Application.
AB  - Integrated navigation algorithms under the grid frame have been proposed based on
      the Kalman filter (KF) to solve the problem of navigation in some special
      regions. However, in the existing study of grid strapdown inertial navigation
      system (SINS)/Doppler velocity log (DVL) integrated navigation algorithms, the
      Earth models of the filter dynamic model and the SINS mechanization are not
      unified. Besides, traditional integrated systems with the KF based correction
      scheme are susceptible to measurement errors, which would decrease the accuracy
      and robustness of the system. In this paper, an adaptive robust Kalman filter
      (ARKF) based hybrid-correction grid SINS/DVL integrated navigation algorithm is
      designed with the unified reference ellipsoid Earth model to improve the
      navigation accuracy in middle-high latitude regions for marine application.
      Firstly, to unify the Earth models, the mechanization of grid SINS is introduced
      and the error equations are derived based on the same reference ellipsoid Earth
      model. Then, a more accurate grid SINS/DVL filter model is designed according to
      the new error equations. Finally, a hybrid-correction scheme based on the ARKF is
      proposed to resist the effect of measurement errors. Simulation and experiment
      results show that, compared with the traditional algorithms, the proposed
      navigation algorithm can effectively improve the navigation performance in middle
      high latitude regions by the unified Earth models and the ARKF based hybrid
      correction scheme.

PMID- 29373545
TI  - Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central
      Nervous System: A Potential Neurological Combinatory Therapy?
AB  - This brief review of the neurological effects of growth hormone (GH) and
      gonadotropin-releasing hormone (GnRH) in the brain, particularly in the cerebral
      cortex, hypothalamus, hippocampus, cerebellum, spinal cord, neural retina, and
      brain tumors, summarizes recent information about their therapeutic potential as
      treatments for different neuropathologies and neurodegenerative processes. The
      effect of GH and GnRH (by independent administration) has been associated with
      beneficial impacts in patients with brain trauma and spinal cord injuries. Both
      GH and GnRH have demonstrated potent neurotrophic, neuroprotective, and
      neuroregenerative action. Positive behavioral and cognitive effects are also
      associated with GH and GnRH administration. Increasing evidence suggests the
      possibility of a multifactorial therapy that includes both GH and GnRH.

PMID- 29373550
TI  - A Fiber Bragg Grating-Based Dynamic Tension Detection System for Overhead
      Transmission Line Galloping.
AB  - Galloping of overhead transmission lines (OHTLs) may induce conductor breakage
      and tower collapse, and there is no effective method for long distance
      distribution on-line galloping monitoring. To overcome the drawbacks of the
      conventional galloping monitoring systems, such as sensitivity to electromagnetic
      interference, the need for onsite power, and short lifetimes, a novel optical
      remote passive measuring system is proposed in the paper. Firstly, to solve the
      hysteresis and eccentric load problem in tension sensing, and to extent the
      dynamic response range, an 'S' type elastic element structure with flanges was
      proposed. Then, a tension experiment was carried out to demonstrate the dynamic
      response characteristics. Moreover, the designed tension sensor was stretched
      continuously for 30 min to observe its long time stability. Last but not the
      least, the sensor was mounted on a 70 m conductor model, and the conductor was
      oscillated at different frequencies to investigate the dynamic performance of the
      sensor. The experimental results demonstrate the sensor is suitable for the OHTL
      galloping detection. Compared with the conventional sensors for OHTL monitoring,
      the system has many advantages, such as easy installation, no flashover risk,
      distribution monitoring, better bandwidth, improved accuracy and higher
      reliability.

PMID- 29373547
TI  - The Effect of Triptolide in Rheumatoid Arthritis: From Basic Research towards
      Clinical Translation.
AB  - Triptolide (TP), a major extract of the herb Tripterygium wilfordii Hook F
      (TWHF), has been shown to exert potent pharmacological effects, especially an
      immunosuppressive effect in the treatment of rheumatoid arthritis (RA). However,
      its multiorgan toxicity prevents it from being widely used in clinical practice.
      Recently, several attempts are being performed to reduce TP toxicity. In this
      review, recent progress in the use of TP for RA, including its pharmacological
      effects and toxicity, is summarized. Meanwhile, strategies relying on chemical
      structural modifications, innovative delivery systems, and drug combinations to
      alleviate the disadvantages of TP are also reviewed. Furthermore, we also discuss
      the challenges and perspectives in their clinical translation.

PMID- 29373551
TI  - Depression in Intimate Partner Violence Victims in Slovenia: A Crippling Pattern
      of Factors Identified in Family Practice Attendees.
AB  - This multi-centre cross-sectional study explored associations between prevalence
      of depression and exposure to intimate partner violence (IPV) at any time in
      patients' adult life in 471 participants of a previous IPV study. In 2016, 174
      interviews were performed, using the Short Form Domestic Violence Exposure
      Questionnaire, the Zung Scale and questions about behavioural patterns of
      exposure to IPV. Family doctors reviewed patients' medical charts for period from
      2012 to 2016, using the Domestic Violence Exposure Medical Chart Check List, for
      conditions which persisted for at least three years. Depression was found to be
      associated with any exposure to IPV in adult life and was more likely to affect
      women. In multivariable logistic regression modelling, factors associated with
      self-rated depression were identified (p < 0.05). Exposure to emotional and
      physical violence was identified as a risk factor in the first model, explaining
      23% of the variance. The second model explained 66% of the variance; past
      divorce, dysfunctional family relationships and a history of incapacity to work
      increased the likelihood of depression in patients. Family doctors should
      consider IPV exposure when detecting depression, since lifetime IPV exposure was
      found to be 40.4% and 36.9% of depressed revealed it.

PMID- 29373552
TI  - Self-Assembled Supramolecular Nanoparticles Improve the Cytotoxic Efficacy of CK2
      Inhibitor THN7.
AB  - Since the approval of imatinib in 2001, kinase inhibitors have revolutionized
      cancer therapies. Inside this family of phosphotransferases, casein kinase 2
      (CK2) is of great interest and numerous scaffolds have been investigated to
      design CK2 inhibitors. Recently, functionalized indeno[1,2-b]indoles have been
      revealed to have high potency against human cancer cell lines such as MCF-7
      breast carcinoma and A-427 lung carcinoma. 4-Methoxy-5-isopropyl-5,6,7,8
      tetrahydroindeno[1,2-b]indole-9,10-dione (THN7), identified as a potent inhibitor
      of CK2 (IC50 = 71 nM), was selected for an encapsulation study in order to
      evaluate its antiproliferative activity as THN7-loaded cyclodextrin
      nanoparticles. Four alpha-cyclodextrins (alpha-CDs) were selected to encapsulate
      THN7 and all experiments indicated that the nanoencapsulation of this CK2
      inhibitor in alpha-CDs was successful. No additional surface-active agent was
      used during the nanoformulation process. Nanoparticles formed between THN7 and
      alpha-C6H13 amphiphilic derivative gave the best results in terms of
      encapsulation rate (% of associated drug = 35%), with a stability constant (K11)
      of 298 mol.L-1 and a size of 132 nm. Hemolytic activity of the four alpha-CDs was
      determined before the in cellulo evaluation and the alpha-C6H13 derivative gave
      the lowest value of hemolytic potency (HC50 = 1.93 mol.L-1). Only the THN7-loaded
      cyclodextrin nanoparticles showing less toxicity on human erythrocytes (alpha
      C6H13, alpha-C8H17 and alpha-C4H9) were tested against A-427 cells. All drug
      loaded nanoparticles caused more cytotoxicity against A-427 cells than THN7
      alone. Based on these results, the use of amphiphilic CD nanoparticles could be
      considered as a drug delivery system for indeno[1,2-b]indoles, allowing an
      optimized bioavailability and offering perspectives for the in vivo development
      of CK2 inhibitors.

PMID- 29373553
TI  - Anti-Inflammatory and Antitumor Effects of Hydroxytyrosol but Not Oleuropein on
      Experimental Glioma In Vivo. A Putative Role for the Renin-Angiotensin System.
AB  - Functional roles of the angiotensin peptides of the renin-angiotensin system
      (RAS) cascade can be analyzed through their corresponding proteolytic regulatory
      enzymes aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase B
      (APB), aminopeptidase N (APN) and insulin-regulated aminopeptidase (IRAP). These
      enzyme activities generate active or inactive angiotensin peptides that alter the
      ratios between their bioactive forms, regulating several important processes such
      as the regulation of cardiovascular functions, body water regulation, normal
      memory consolidation and retrieval, but also cell growth, differentiation and
      apoptosis or the inflammatory response. We have previously described that the
      treatment with hydroxytyrosol but not with oleuropein or with the mixture of both
      compounds led to the significant inhibition of tumor growth in an in vivo glioma
      model by mechanisms not only related to redox balance. Using this glioma model,
      here we analyze the effects of the phenolic compounds oleuropein and
      hydroxytyrosol in circulating RAS-regulating ASAP, APA, APN, APB and IRAP
      specific activities and the pro-inflammatory cytokines IL-6 and TNFalpha to
      understand the relationship between the antitumor and anti-inflammatory effects
      of hydroxytyrosol, but not oleuropein, and the components of the RAS. We found
      that oleuropein increased all the activities analyzed and promoted a pro
      inflammatory status, whereas hydroxytyrosol only modified ASAP and IRAP
      activities and promotes an anti-inflammatory status. When administrated together,
      oleuropein overrode the effects of hydroxytyrosol. Our results suggest a role for
      angiotensin III and angiotensin 1-7 in both tumor growth inhibition and anti
      inflammatory response promoted by hydroxytyrosol.

PMID- 29373554
TI  - The Effect of Childhood Health Status on Adult Health in China.
AB  - Childhood health in China was poor in the 1950s and 1960s because of limited
      nutrition. In the last three decades, China has distinguished itself through its
      tremendous economic growth and improvements in health and nutrition. However,
      prior to such growth, access to good nutrition was more variable, with
      potentially important implications, not only for childhood health, but also for
      adult health, because of its long-term effects lasting into adulthood. To shed
      light on these issues, this study examined the long-run association between
      childhood health and adult health outcomes among a middle-aged Chinese population
      and addresses the endogeneity of childhood health. A nationwide database from the
      2011 China Health and Retirement Longitudinal Study (CHARLS) was employed. Three
      adult health outcomes variables were used: self-reported health status,
      cognition, and physical function. The local variation in grain production in the
      subjects' fetal period and the first 24 months following birth was employed as an
      instrument for childhood health in order to correct for its endogeneity.
      Childhood health recalled by the respondents was positively and significantly
      associated with their adult health outcomes in terms of self-reported health
      status, cognition, and physical function in single-equation estimates that did
      not correct for the endogeneity of childhood health. A good childhood health
      status increased the probabilities of good adult health, good adult cognitive
      function, and good adult physical function by 16% (95% CI: 13-18%), 13% (95% CI:
      10-15%), and 14% (95% CI: 12-17%), respectively. After correcting for
      endogeneity, the estimated effects of good childhood health were consistent but
      stronger. We also studied the male and female populations separately, finding
      that the positive effects of childhood health on adult health were larger for
      males. In China, childhood health significantly affects adult health. This
      suggests that early interventions to promote childhood health will have long-term
      benefits in China and that health-care policies should consider their long-term
      impacts over the life cycle in addition to their effects on specific age groups.

PMID- 29373555
TI  - Microstructures and Properties of Laser Cladding Al-TiC-CeO2 Composite Coatings.
AB  - Al-TiC-CeO2 composite coatings have been prepared by using a laser cladding
      technique, and the microstructure and properties of the resulting composite
      coatings have been investigated using scanning electron microscopy (SEM), a 3D
      microscope system, X-ray diffraction (XRD), micro-hardness testing, X-ray stress
      measurements, friction and wear testing, and an electrochemical workstation. The
      results showed that an Al-Fe phase appears in the coatings under different
      applied laser powers and shows good metallurgical bonding with the matrix. The
      dilution rate of the coating first decreases and then increases with increasing
      laser power. The coating was transformed from massive and short rod-like
      structures into a fine granular structure, and the effect of fine grain
      strengthening is significant. The microhardness of the coatings first decreases
      and then increases with increasing laser power, and the maximum microhardness can
      reach 964.3 HV0.2. In addition, the residual stress of the coating surface was
      tensile stress, and crack size increases with increasing stress. When the laser
      power was 1.6 kW, the coating showed high corrosion resistance.

PMID- 29373556
TI  - Long-Term Weight Loss Effects of a Behavioral Weight Management Program: Does the
      Community Food Environment Matter?
AB  - This study examined whether community food environments altered the longer-term
      effects of a nationwide behavioral weight management program on body mass index
      (BMI). The sample was comprised of 98,871 male weight management program
      participants and 15,385 female participants, as well as 461,302 and 37,192
      inverse propensity-score weighted matched male and female controls. We measured
      the community food environment by counting the number of supermarkets,
      convenience stores, and fast food restaurants within a 1-mile radius around each
      person's home address. We used difference-in-difference regression models with
      person and calendar time fixed effects to estimate MOVE! effects over time in sub
      populations defined by community food environment attributes. Among men, after an
      initial decrease in BMI at 6 months, the effect of the program decreased over
      time, with BMI increasing incrementally at 12 months (0.098 kg/m2, p < 0.001), 18
      months (0.069 kg/m2, p < 0.001), and 24 months (0.067 kg/m2, p < 0.001). Among
      women, the initial effects of the program decreased over time as well. Women had
      an incremental BMI change of 0.099 kg/m2 at 12 months (p < 0.05) with non
      significant incremental changes at 18 months and 24 months. We found little
      evidence that these longer-term effects of the weight management program differed
      depending on the community food environment. Physiological adaptations may
      overwhelm environmental influences on adherence to behavioral regimens in
      affecting longer-term weight loss outcomes.

PMID- 29373558
TI  - Physiological Effects of Visual Stimulation with Forest Imagery.
AB  - This study was aimed to clarify the physiological effects of visual stimulation
      using forest imagery on activity of the brain and autonomic nervous system.
      Seventeen female university students (mean age, 21.1 +/- 1.0 years) participated
      in the study. As an indicator of brain activity, oxyhemoglobin (oxy-Hb)
      concentrations were measured in the left and right prefrontal cortex using near
      infrared time-resolved spectroscopy. Heart rate variability (HRV) was used as an
      indicator of autonomic nervous activity. The high-frequency (HF) component of
      HRV, which reflected parasympathetic nervous activity, and the ratio of low
      frequency (LF) and high-frequency components (LF/HF), which reflected sympathetic
      nervous activity, were measured. Forest and city (control) images were used as
      visual stimuli using a large plasma display window. After sitting at rest viewing
      a gray background for 60 s, participants viewed two images for 90 s. During rest
      and visual stimulation, HRV and oxy-Hb concentration in the prefrontal cortex
      were continuously measured. Immediately thereafter, subjective evaluation of
      feelings was performed using a modified semantic differential (SD) method. The
      results showed that visual stimulation with forest imagery induced (1) a
      significant decrease in oxy-Hb concentrations in the right prefrontal cortex and
      (2) a significant increase in perceptions of feeling "comfortable," "relaxed,"
      and "natural."

PMID- 29373559
TI  - Data Analyses and Modelling for Risk Based Monitoring of Mycotoxins in Animal
      Feed.
AB  - Following legislation, European Member States should have multi-annual control
      programs for contaminants, such as for mycotoxins, in feed and food. These
      programs need to be risk based implying the checks are regular and proportional
      to the estimated risk for animal and human health. This study aimed to prioritize
      feed products in the Netherlands for deoxynivalenol and aflatoxin B1 monitoring.
      Historical mycotoxin monitoring results from the period 2007-2016 were combined
      with data from other sources. Based on occurrence, groundnuts had high priority
      for aflatoxin B1 monitoring; some feed materials (maize and maize products and
      several oil seed products) and complete/complementary feed excluding dairy cattle
      and young animals had medium priority; and all other animal feeds and feed
      materials had low priority. For deoxynivalenol, maize by-products had a high
      priority, complete and complementary feed for pigs had a medium priority and all
      other feed and feed materials a low priority. Also including health consequence
      estimations showed that feed materials that ranked highest for aflatoxin B1
      included sunflower seed and palmkernel expeller/extracts and maize. For
      deoxynivalenol, maize products were ranked highest, followed by various small
      grain cereals (products); all other feed materials were of lower concern. Results
      of this study have proven to be useful in setting up the annual risk based
      control program for mycotoxins in animal feed and feed materials.

PMID- 29373557
TI  - Autoimmunity and Gastric Cancer.
AB  - Alterations in the immune response of patients with autoimmune diseases may
      predispose to malignancies, and a link between chronic autoimmune gastritis and
      gastric cancer has been reported in many studies. Intestinal metaplasia with
      dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin
      cells, which are typical features of late-stage autoimmune gastritis, are
      considered precursor lesions. Autoimmune gastritis has been associated with the
      development of two types of gastric neoplasms: intestinal type and type I gastric
      carcinoid. Here, we review the association of autoimmune gastritis with gastric
      cancer and other autoimmune features present in gastric neoplasms.

PMID- 29373560
TI  - Effect of Temperature on Flavor Compounds and Sensory Characteristics of Maillard
      Reaction Products Derived from Mushroom Hydrolysate.
AB  - Maillard reaction products (MRPs) were prepared from mushroom hydrolysate (MH) by
      heating with d-xylose and l-cysteine at various temperatures (100  degrees C-140 
      degrees C) for 2 h at a pH of 7.4. The sensory characteristics of MH and MRPs
      were evaluated by panelists and volatile compounds were analyzed by GC/MS.
      Additionally, partial least squares regression (PLSR) was performed to analyze
      the correlation between quantitative sensory characteristics and GC/MS data.
      GC/MS results revealed that higher reaction temperature resulted in more nitrogen
      and sulfur containing compounds in MRPs while alcohols, ketones and aldehydes
      were the major flavor compounds obtained in MH. PLSR results showed that 3
      phenylfuran and 2-octylfuran were the compounds responsible for the caramel-like
      flavor; 1-octen-3-ol, (E)-2-octen-1-ol and geranyl acetone were significantly and
      positively correlated to mushroom-like flavor, whereas, 2-thiophene
      carboxaldehyde, 2,5-thiophenedicarboxaldehyde and 3-methylbutanal positively
      affected MRPs meat-like attribute. Overall, 125  degrees C was identified as the
      optimal temperature for preparing MRPs with abundant volatile compounds and
      favorable sensory characteristics; the concentration of free amino acids and 5'
      GMP, which are associated with the umami taste, in MRPs derived under 125 
      degrees C were 3 to 4 times higher than those in MH.

PMID- 29373561
TI  - Sex-Specific Associations in Nutrition and Activity-Related Risk Factors for
      Chronic Disease: Australian Evidence from Childhood to Emerging Adulthood.
AB  - Global assessments of burden of disease suggests there are sex differences in
      risk factors for chronic disease, including overweight/obesity, dietary patterns
      and habitual physical activity. Given that prevention efforts aim to target such
      factors to reduce disease risk, the age at which sex differences may occur is of
      particular interest. Early life to young adulthood is the optimal time for
      intervention, with lifestyle habits typically forming during this period. This
      study aimed to identify the sex differences in risk factors for chronic disease
      during childhood (5-9 years), adolescence (10-17 years) and emerging adulthood
      (18-25 years) in a large population-representative Australian sample. Among
      children in this study (n = 739), no sex-related differences were observed. Among
      adolescents (n = 1304), females were more likely than males to meet daily fruit
      and vegetable recommendations (12.9% vs. 7.5%; OR = 1.84, 95% CI = 1.16, 2.93, p
      < 0.05). Among emerging adults (n = 909), females were less likely to be
      overweight/obese (30.1% vs. 39.8%; OR = 0.65, 95% CI = 0.44, 0.95, p < 0.05) and
      more likely to meet physical activity recommendations (52.1% vs. 42.3%; OR =
      1.44, 95% CI = 1.01, 2.06, p < 0.05). These findings suggest that sex differences
      for risk factors of chronic disease occur during adolescence and emerging
      adulthood, although the differences are not consistent across age periods. From
      adolescence onwards, it appears that females exhibit lower risk factors than
      males and a life span approach to risk factor monitoring is warranted.

PMID- 29373562
TI  - Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein
      Expressed Using ExpressTec.
AB  - Proinsulin-transferrin fusion protein (ProINS-Tf) has been designed and
      successfully expressed from the mammalian HEK293 cells (HEK-ProINS-Tf). It was
      found that HEK-ProINS-Tf could be converted into an activated form in the liver.
      Furthermore, HEK-ProINS-Tf was demonstrated as an extra-long acting insulin
      analogue with liver-specific insulin action in streptozotocin (STZ)-induced type
      1 diabetic mice. However, due to the low production yield from transfected HEK293
      cells, there are other interesting features, including the oral bioavailability,
      which have not been fully explored and characterized. To improve the protein
      production yield, an alternative protein expression system, ExpressTec using
      transgenic rice (Oryza sativa L.), was used. The intact and active rice-derived
      ProINS-Tf (ExpressTec-ProINS-Tf) was successfully expressed from the transgenic
      rice expression system. Our results suggested that, although the insulin-like
      bioactivity of ExpressTec-ProINS-Tf was slightly lower in vitro, its potency of
      in vivo blood glucose control was considerably stronger than that of HEK-ProINS
      Tf. The oral delivery studies in type 1 diabetic mice demonstrated a prolonged
      control of blood glucose to near-normal levels after oral administration of
      ExpressTec-ProINS-Tf. Results in this report suggest that ExpressTec-ProINS-Tf is
      a promising insulin analog with advantages including low cost, prolonged and
      liver targeting effects, and most importantly, oral bioactivity.

PMID- 29373563
TI  - Study of Stroke Incidence in the Aseer Region, Southwestern Saudi Arabia.
AB  - Recent data regarding first-stroke incidence in Saudi Arabia in general and in
      the Aseer region in particular are scarce and even lacking. The aim of this work
      was to study the first-time stroke incidence in the Aseer region, southwestern
      Saudi Arabia. All first-stroke patients admitted to all hospitals in the Aseer
      region over a one-year period (January through December 2016) were included.
      Stroke patients outside the Aseer region were excluded from the study. The
      incidence per 100,000 patients and the concomitant 95% CI (Confidence Intervals)
      were computed. The present study included 1249 first-time stroke patients and
      calculated an overall minimal incidence rate of hospitalized first-time stroke of
      57.64 per 100,000 persons per year (95% CI: 57.57-57.70). A steady increase was
      noticed depending on the patients' age, reaching a figure of 851.81 (95% CI:
      849.2-854.5) for those patients aged 70 years and more. Overall, the incidence
      rate for females (48.14; 95% CI: 48.04-48.24) was lower compared to males (65.52;
      95% CI: 65.1-66.0). Taking into consideration the expected rise of the elderly
      because of the prominent medical services provided by the Saudi government,
      leading to a subsequent change in the horizontal and vertical age distribution
      structure of the population, an increase in the number of stroke patients is
      expected. It is suggested to establish a nationwide stroke surveillance system in
      the Kingdom, with the objective to report, analyze, and maintain an updated
      overview of the stroke status in Saudi Arabia.

PMID- 29373565
TI  - Intention for Car Use Reduction: Applying a Stage-Based Model.
AB  - This study investigates which variables drive intention to reduce car use by
      modelling a stage of change construct with mechanisms in the Theory of Planned
      Behavior (TPB) and Norm Activation Model (NAM). Web questionnaires (n = 794) were
      collected via 11 workplaces. The socio-demographics, work commute, stage of
      change, attitudes to sustainable travel modes, social norms, perceived behavioral
      control, and personal norm were assessed. An initial descriptive analysis
      revealed that 19% of the employees saw no reason to reduce their car use; 35%
      would like to reduce their car use but felt it was impossible; 12% were thinking
      about reducing their car use but were unsure of how or when to do this; 12% had
      an aim to reduce current car use, and knew which journeys to replace and which
      modes to use; and 23% try to use modes other than a car for most journeys, and
      will maintain or reduce their already low car use in the coming months. A series
      of Ordered Logit Models showed that socio-demographic variables did not explain
      the stage of change. Instead, personal norms, instrumental and affective
      attitudes, and perceived behavioral control toward sustainable travel modes were
      all significant and explained 43% of the variance in stage of change.
      Furthermore, it was found that the significant relationships were not linear in
      nature. The analysis also showed an indirect effect of social norms on the stage
      of change through personal norms. Implications are discussed regarding the design
      of interventions aimed at influencing a sustainable work commute.

PMID- 29373566
TI  - Cistus incanus from Strandja Mountain as a Source of Bioactive Antioxidants.
AB  - The purpose of the present study is to survey the extraction conditions and
      explore the antioxidant potential of the wild herb Cistus incanus, which is non
      traditional in Bulgarian ethnomedicine and widespread in the Strandja Mountain.
      The influence of the extraction time (0-500 min) and solvent composition (0-50%
      ethanol in water) on the polyphenols, flavonoid yields and on the antioxidant
      capacity of the extracts of leaves, stalks (wood parts) and bud mixture were
      studied. The antioxidant capacity (AOC) was evaluated by use of scavenging assays
      of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. Total polyphenol and flavonoid
      contents were quantified using UV-vis (ultraviolet-visible) spectrophotometry.
      The optimal yield of the desired components was obtained with 30% ethanol in
      water solvent at the 390th min of extraction time. In addition, the influence of
      seasonality (winter and summer Cistus incanus), and of the different aerial parts
      hard-coated seeds, buds, and a mixture of leaves and stalks of the wild plant-on
      the presence of polyphenols, flavonoids, and AOC were investigated. The present
      work revealed that the high values of polyphenols, flavonoids and the high AOC
      occurred not only in the summer leaves, but were also found in the winter leaves,
      hard-coated seeds, buds, and stalks. Based on the obtained results, the Cistus
      incanus from Strandja Mountain could be an excellent new source of natural
      antioxidants in food and for the pharmaceutical industries.

PMID- 29373567
TI  - Do Natural Experiments of Changes in Neighborhood Built Environment Impact
      Physical Activity and Diet? A Systematic Review.
AB  - Physical activity and diet are major modifiable risk factors for chronic disease
      and have been shown to be associated with neighborhood built environment.
      Systematic review evidence from longitudinal studies on the impact of changing
      the built environment on physical activity and diet is currently lacking. A
      systematic review of natural experiments of neighborhood built environment was
      conducted. The aims of this systematic review were to summarize study
      characteristics, study quality, and impact of changes in neighborhood built
      environment on physical activity and diet outcomes among residents. Natural
      experiments of neighborhood built environment change, exploring longitudinal
      impacts on physical activity and/or diet in residents, were included. From five
      electronic databases, 2084 references were identified. A narrative synthesis was
      conducted, considering results in relation to study quality. Nineteen papers,
      reporting on 15 different exposures met inclusion criteria. Four studies included
      a comparison group and 11 were pre-post/longitudinal studies without a comparison
      group. Studies reported on the impact of redeveloping or introducing cycle and/or
      walking trails (n = 5), rail stops/lines (n = 4), supermarkets and farmers'
      markets (n = 4) and park and green space (n = 2). Eight/15 studies reported at
      least one beneficial change in physical activity, diet or another associated
      health outcome. Due to limitations in study design and reporting, as well as the
      wide array of outcome measures reported, drawing conclusions to inform policy was
      challenging. Future research should consider a consistent approach to measure the
      same outcomes (e.g., using measurement methods that collect comparable physical
      activity and diet outcome data), to allow for pooled analyses. Additionally,
      including comparison groups wherever possible and ensuring high quality reporting
      is essential.

PMID- 29373568
TI  - Current Age, Age at First Sex, Age at First Homelessness, and HIV Risk
      Perceptions Predict Sexual Risk Behaviors among Sexually Active Homeless Adults.
AB  - While HIV disproportionately impacts homeless individuals, little is known about
      the prevalence of HIV risk behaviors in the southwest and how age factors and HIV
      risk perceptions influence sexual risk behaviors. We conducted a secondary data
      analysis (n = 460) on sexually active homeless adults from a cross-sectional
      study of participants (n = 610) recruited from homeless service locations, such
      as shelters and drop-in centers, in an understudied region of the southwest.
      Covariate-adjusted logistic regressions were used to assess the impact of age at
      homelessness onset, current age, age at first sex, and HIV risk perceptions on
      having condomless sex, new sexual partner(s), and multiple sexual partners (>=4
      sexual partners) in the past 12 months. Individuals who first experienced
      homelessness by age 24 were significantly more likely to report condomless sex
      and multiple sexual partners in the past year than those who had a later onset of
      their first episode of homelessness. Individuals who were currently 24 years or
      younger were more likely to have had condomless sex, new sexual partners, and
      multiple sexual partners in the past 12 months than those who were 25 years or
      older. Those who had low perceived HIV risk had lower odds of all three sexual
      risk behaviors. Social service and healthcare providers should consider a younger
      age at homelessness onset when targeting HIV prevention services to youth
      experiencing homelessness.

PMID- 29373569
TI  - Efficacy and Acceptability of 1 Liter of Polyethylene Glycol with Ascorbic Acid
      vs. 2 Liters of Polyethylene Glycol Plus Mosapride and Sennoside for Colonoscopy
      Preparation.
AB  - BACKGROUND [color=black]Bowel preparation is an important factor for an optimal
      outcome of colonoscopy. Recently, polyethylene glycol (PEG) solution has been in
      common use for bowel cleansing for colonoscopy, but some patients are intolerant
      of PEG because of taste or volume. A low-volume PEG administered with ascorbic
      acid solution (PEG-Asc) was designed to improve tolerability, but the
      administration of this method is more complex than that with PEG alone. This
      study aimed to compare bowel cleansing efficacy, safety, and tolerability of 1 L
      PEG-Asc with a 2 L PEG preparation with use of sennosides and mosapride.[/color]
      MATERIAL AND METHODS [color=black]This was a prospective, single-center, non
      inferiority trial that included 112 patients (PEG-Asc group, 68; PEG group, 44).
      The primary endpoint was the efficacy of colon cleansing assessed by endoscopists
      using a validated 4-point scale according to the Aronchick scale and was verified
      by a blinded investigator. Acceptability, tolerability, and adenoma detection
      rate (ADR) of these 2 regimens were secondary endpoints.[/color][color=black]
      [/color] RESULTS [color=black]We found no statistically significant differences
      between the groups in colon-cleansing efficacy or in the adenoma detection rate
      (ADR). Moreover, overall, patients significantly favored PEG-Asc over PEG,
      reflecting better acceptance of PEG-Asc. Additionally, more patients favored PEG
      Asc over PEG for a hypothetical future colonoscopy. [/color] CONCLUSIONS
      [color=black]The alternate 1 L PEG-Asc regimen and standard 2 L PEG regimen were
      clinically equivalent with respect to cleansing efficacy, safety, and ADR, and
      more patients favored PEG-Asc than PEG. This alternate regimen may improve
      patient compliance and acceptance of surveillance colonoscopy.[/color].

PMID- 29373570
TI  - Do cannabinoids play a role in the control of glaucoma?
AB  - INTRODUCTION: The use of cannabinoids in diverse clinical conditions is today a
      subject of debate. Its use has been proposed for the control of glaucoma.
      However, there is controversy about its real effectiveness and safety. METHODS:
      To answer this question we used Epistemonikos, the largest database of systematic
      reviews in health, which is maintained by screening multiple information sources,
      including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the
      systematic reviews, reanalyzed data of primary studies and generated a summary of
      findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified
      five systematic reviews including three studies overall, all of them randomized
      controlled trials. We concluded that although cannabinoids could decrease
      intraocular pressure, the effect would be transient and associated with frequent
      adverse effects.

PMID- 29373571
TI  - The microenvironment of classical Hodgkin lymphoma: heterogeneity by Epstein-Barr
      virus presence and location within the tumor.
AB  - This corrects the article DOI: 10.1038/bcj.2016.26.

PMID- 29373564
TI  - Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z.
AB  - Galectin-3 (Gal-3) regulates basic cellular functions such as cell-cell and cell
      matrix interactions, growth, proliferation, differentiation, and inflammation. It
      is not surprising, therefore, that this protein is involved in the pathogenesis
      of many relevant human diseases, including cancer, fibrosis, chronic inflammation
      and scarring affecting many different tissues. The papers published in the
      literature have progressively increased in number during the last decades,
      testifying the great interest given to this protein by numerous researchers
      involved in many different clinical contexts. Considering the crucial role
      exerted by Gal-3 in many different clinical conditions, Gal-3 is emerging as a
      new diagnostic, prognostic biomarker and as a new promising therapeutic target.
      The current review aims to extensively examine the studies published so far on
      the role of Gal-3 in all the clinical conditions and diseases, listed in
      alphabetical order, where it was analyzed.

PMID- 29373572
TI  - Intraspecific variation in oxidative stress tolerance in a model cnidarian:
      Differences in peroxide sensitivity between and within populations of
      Nematostella vectensis.
AB  - Nematostella vectensis is a member of the phylum Cnidaria, a lineage that
      includes anemones, corals, hydras, and jellyfishes. This estuarine anemone is an
      excellent model system for investigating the evolution of stress tolerance
      because it is easy to collect in its natural habitat and to culture in the
      laboratory, and it has a sequenced genome. Additionally, there is evidence of
      local adaptation to environmental stress in different N. vectensis populations,
      and abundant protein-coding polymorphisms have been identified, including
      polymorphisms in proteins that are implicated in stress responses. N. vectensis
      can tolerate a wide range of environmental parameters, and has recently been
      shown to have substantial intraspecific variation in temperature preference. We
      investigated whether different clonal lines of anemones also exhibit differential
      tolerance to oxidative stress. N. vectensis populations are continually exposed
      to reactive oxygen species (ROS) generated during cellular metabolism and by
      other environmental factors. Fifteen clonal lines of N. vectensis collected from
      four different estuaries were exposed to hydrogen peroxide. Pronounced
      differences in survival and regeneration were apparent between clonal lines
      collected from Meadowlands, NJ, Baruch, SC, and Kingsport, NS, as well as among
      12 clonal lines collected from a single Cape Cod marsh. To our knowledge, this is
      the first example of intraspecific variability in oxidative stress resistance in
      cnidarians or in any marine animal. As oxidative stress often accompanies heat
      stress in marine organisms, resistance to oxidative stress could strongly
      influence survival in warming oceans. For example, while elevated temperatures
      trigger bleaching in corals, oxidative stress is thought to be the proximal
      trigger of bleaching at the cellular level.

PMID- 29373573
TI  - Maternal obesity increases insulin resistance, low-grade inflammation and
      osteochondrosis lesions in foals and yearlings until 18 months of age.
AB  - INTRODUCTION: Obesity is a growing concern in horses. The effects of maternal
      obesity on maternal metabolism and low-grade inflammation during pregnancy, as
      well as offspring growth, metabolism, low-grade inflammation, testicular
      maturation and osteochondrotic lesions until 18 months of age were investigated.
      MATERIAL AND METHODS: Twenty-four mares were used and separated into two groups
      at insemination according to body condition score (BCS): Normal (N, n = 10, BCS
      <=4) and Obese (O, n = 14, BCS >=4.25). BCS and plasma glucose, insulin,
      triglyceride, urea, non-esterified fatty acid, serum amyloid A (SAA), leptin and
      adiponectin concentrations were monitored throughout gestation. At 300 days of
      gestation, a Frequently Sampled Intravenous Glucose Tolerance Test (FSIGT) was
      performed. After parturition, foals' weight and size were monitored until 18
      months of age with plasma SAA, leptin, adiponectin, triiodothyronine (T3),
      thyroxine (T4) and cortisol concentrations measured at regular intervals. At 6,
      12 and 18 months of age, FSIGT and osteoarticular examinations were performed.
      Males were gelded at one year and expression of genes involved in testicular
      maturation analysed by RT-qPCR. RESULTS: Throughout the experiment, maternal BCS
      was higher in O versus N mares. During gestation, plasma urea and adiponectin
      were decreased and SAA and leptin increased in O versus N mares. O mares were
      also more insulin resistant than N mares with a higher glucose effectiveness.
      Postnatally, there was no difference in offspring growth between groups.
      Nevertheless, plasma SAA concentrations were increased in O versus N foals until
      6 months, with O foals being consistently more insulin resistant with a higher
      glucose effectiveness. At 12 months of age, O foals were significantly more
      affected by osteochondrosis than N foals. All other parameters were not different
      between groups. CONCLUSION: In conclusion, maternal obesity altered metabolism
      and increased low-grade inflammation in both dams and foals. The risk of
      developing osteochondrosis at 12 months of age was also higher in foals born to
      obese dams.

PMID- 29373574
TI  - Loss to follow-up before and after initiation of antiretroviral therapy in HIV
      facilities in Lilongwe, Malawi.
AB  - INTRODUCTION: Although several studies have explored factors associated with loss
      to follow-up (LTFU) from HIV care, there remains a gap in understanding how these
      factors vary by setting, volume of patient and patients' demographic and clinical
      characteristics. We determined rates and factors associated with LTFU in HIV care
      Lilongwe, Malawi. METHODS: We conducted a retrospective cohort study of HIV
      infected individuals aged 15 years or older at the time of registration for HIV
      care in 12 ART facilities, between April 2012 and March 2013. HIV-positive
      individuals who had not started ART (pre-ART patients) were clinically assessed
      to determine ART eligibility at registration and during clinic follow-up visits.
      ART-eligible patients were initiated on triple antiretroviral combination. Study
      data were abstracted from patients' cards, facility ART registers or electronic
      medical record system from the date of registration for HIV care to a maximum
      follow-up period of 24 months. Descriptive statistics were undertaken to
      summarize characteristics of the study patients. Separate univariable and
      multivariable poisson regression models were used to explore factors associated
      with LTFU in pre-ART and ART care. RESULTS: A total of 10,812 HIV-infected
      individuals registered for HIV care. Of these patients, 1,907 (18%) and 8,905
      (82%) enrolled in pre-ART and ART care, respectively. Of the 1,907 pre-ART
      patients, 490 (26%) subsequently initiated ART and were included in both the pre
      ART and ART analyses. The LTFU rates among patients in pre-ART and ART care were
      48 and 26 per 100 person-years, respectively. Of the 9,105 ART patients with
      reasons for starting ART, 2,451 (27%) were initiated on ART because of pregnancy
      or breastfeeding (Option B+) status. Multivariable analysis showed that being
      >=35 years and female were associated with decreased risk of LTFU in the pre-ART
      and ART phases of HIV care. However, being in WHO clinical stage 3 (adjusted risk
      ratio (aRR) 1.35, 95% confidence interval (CI): 1.20-1.51) and stage 4 (aRR 1.87,
      95% CI: 1.62-2.18), body mass index <= 18.4 (aRR 1.24, 95% CI: 1.11-1.39) at ART
      initiation, poor adherence to clinic appointments (aRR 4.55, 95% CI: 4.16-4.97)
      and receiving HIV care in rural facilities (aRR 2.32, 95% CI: 1.94-2.87) were
      associated with increased risk of LTFU among ART patients. Being re-initiated on
      ART once (aRR 0.20, 95% CI: 0.17-0.22), more than once (aRR 0.06, 95% CI: 0.05
      0.07), and being enrolled at a low-volume facility (aRR 0.25, 95% CI: 0.20-0.30)
      were associated with decreased risk of LTFU from ART care. CONCLUSION: A sizeable
      proportion of ART LTFU occurred among women enrolled during pregnancy or breast
      feeding. Non- compliance to clinic and receiving ART in a rural facility or high
      volume facility were associated with increased risk of LTFU from ART care.
      Developing effective interventions that target high-risk subgroups and contexts
      may help reduce LTFU from HIV care.

PMID- 29373575
TI  - Biochar amendment changes jasmonic acid levels in two rice varieties and alters
      their resistance to herbivory.
AB  - Biochar addition to soil not only sequesters carbon for the long-term but
      enhances agricultural productivity. Several well-known benefits arise from
      biochar amendment, including constant provision of nutrients, increased soil
      moisture retention, decreased soil bulk density, and sometimes the induction of
      systemic resistance against foliar and soil borne plant pathogens. However, no
      research has investigated the potential of biochar to increase resistance against
      herbivory. The white-backed plant hopper (WBPH) (Sogatella furcifera Horvath) is
      a serious agricultural pest that targets rice (Oryza sativa L.), a staple crop
      that feeds half of the world's human population. Therefore, we investigated the
      (1) optimization of biochar amendment levels for two rice varieties
      ('Cheongcheong' and 'Nagdong') and (2) subsequent effects of different biochar
      amendments on resistance and susceptibility of these two varieties to WBPH
      infestation. Initial screening results for the optimization level revealed that
      the application of biochar 10% (w/w) to the rooting media significantly improved
      plant physiological characteristics of both rice varieties. However, levels of
      biochar amendment, mainly 1, 2, 3, and 20%, resulted in negative effects on plant
      growth characteristics. Cheongcheong and Nagdong rice plants grown with the
      optimum biochar level showed contrasting reactions to WBPH infestation.
      Specifically, biochar application significantly increased plant growth
      characteristics of Nagdong when exposed to WBPH infestation and significantly
      decreased these characteristics in Cheongcheong. The amount of WBPH-induced
      damage to plants was significantly lower and higher in Nagdong and Cheongcheong,
      respectively, compared to that in the controls. Higher levels of jasmonic acid
      caused by the biochar priming effect could have accumulated in response to WBPH
      infestation, resulting in a maladaptive response to stress, negatively affecting
      growth and resistance to WBPH in Cheongcheong. This study highlights the
      importance of investigating the effects of biochar on different rice varieties
      before application on a commercial scale to avoid potential crop losses.

PMID- 29373576
TI  - Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal
      dynamics at the Drosophila neuromuscular junction.
AB  - Retrograde signaling is essential for neuronal growth, function and survival;
      however, we know little about how signaling endosomes might be directed from
      synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a
      plus-end directed microtubule motor protein, as a regulator of sorting of
      endosomes in Drosophila larval motor neurons. The number of synaptic boutons and
      the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular
      junction (NMJ) are normal, but we find a significant decrease in the number of
      presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically
      enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or
      suppressed by activation of BMP signaling in motoneurons. Consistently,
      activation of BMP signaling that normally enhances the accumulation of
      phosphorylated form of BMP transcription factor Mad in the nuclei, can be
      suppressed by genetic removal of Khc-73. Using a number of assays including live
      imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of
      retrograde-bound endosomes to leave the synaptic area and join the retrograde
      axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic
      at the synapse and modulator of retrograde BMP signaling in motoneurons.

PMID- 29373577
TI  - IgA and IgG against Mycobacterium tuberculosis Rv2031 discriminate between
      pulmonary tuberculosis patients, Mycobacterium tuberculosis-infected and non
      infected individuals.
AB  - As part of a major project to investigate protective and diagnostic immune
      markers against tuberculosis (TB), we measured antibody isotype responses to
      Mycobacterium tuberculosis (Mtb) antigens (LAM, Rv2031, and HBHA) in cohorts of
      149 pulmonary tuberculosis patients (PTBP), 148 household contacts (HHCs), and 68
      community controls (CCs) in an endemic setting. ELISA was used to measure levels
      of IgA, IgG, and IgM from sera of cohorts at baseline, and at 6 and 12 months
      from entry. The results show that there were significant differences in IgA, IgG,
      and IgM responses to the different antigens and in the three cohorts. At
      baseline, the level of IgM against RV2031 and LAM did not vary between cohorts,
      but the levels of IgA and IgG against Rv2031 were significantly higher in PTB
      patients than HHCs and CCs, followed by HHCs, and the lowest in CCs. In patients,
      there was a significant variation in antibody responses before and after
      chemotherapy. The levels of IgA and IgG against HBHA, and IgA against Rv2031
      decreased significantly and remained low, while IgA and IgG against LAM increased
      significantly and remained high following chemotherapy. However, the levels of
      IgM against Rv2031 and LAM increased at 6 months but decreased again at 12
      months. IgM against HBHA did not show any significant variation before and after
      chemotherapy. Similarly, there were also significant variations in antibody
      responses in HHCs over time. Our results show that there are significant
      variations in IgA, IgG and IgM responses to the different antigens and in the
      three cohorts, implying that not all antibody isotype responses are markers of
      clinical TB. In addition, the current and previous studies consistently show that
      IgA and IgG against Rv2031 discriminate between clinical disease, Mtb-infected
      and non-infected individuals.

PMID- 29373578
TI  - Diagnostic metabolite biomarkers of chronic typhoid carriage.
AB  - BACKGROUND: Salmonella Typhi and Salmonella Paratyphi A are the agents of enteric
      (typhoid) fever; both can establish chronic carriage in the gallbladder. Chronic
      Salmonella carriers are typically asymptomatic, intermittently shedding bacteria
      in the feces, and contributing to disease transmission. Detecting chronic
      carriers is of public health relevance in areas where enteric fever is endemic,
      but there are no routinely used methods for prospectively identifying those
      carrying Salmonella in their gallbladder. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      aimed to identify biomarkers of Salmonella carriage using metabolite profiling.
      We performed metabolite profiling on plasma from Nepali patients undergoing
      cholecystectomy with confirmed S. Typhi or S. Paratyphi A gallbladder carriage
      (and non-carriage controls) using two-dimensional gas chromatography coupled with
      time-of-flight mass spectrometry (GCxGC-TOFMS) and supervised pattern recognition
      modeling. We were able to significantly discriminate Salmonella carriage samples
      from non-carriage control samples. We were also able to detect differential
      signatures between S. Typhi and S. Paratyphi A carriers. We additionally compared
      carriage metabolite profiles with profiles generated during acute infection;
      these data revealed substantial heterogeneity between metabolites associated with
      acute enteric fever and chronic carriage. Lastly, we found that Salmonella
      carriers could be significantly distinguished from non-carriage controls using
      only five metabolites, indicating the potential of these metabolites as
      diagnostic markers for detecting chronic Salmonella carriers.
      CONCLUSIONS/SIGNIFICANCE: Our novel approach has highlighted the potential of
      using metabolomics to search for diagnostic markers of chronic Salmonella
      carriage. We suggest further epidemiological investigations of these potential
      biomarkers in alternative endemic enteric fever settings.

PMID- 29373580
TI  - Fast and robust shape diameter function.
AB  - The shape diameter function (SDF) is a scalar function defined on a closed
      manifold surface, measuring the neighborhood diameter of the object at each
      point. Due to its pose oblivious property, SDF is widely used in shape analysis,
      segmentation and retrieval. However, computing SDF is computationally expensive
      since one has to place an inverted cone at each point and then average the
      penetration distances for a number of rays inside the cone. Furthermore, the
      shape diameters are highly sensitive to local geometric features as well as the
      normal vectors, hence diminishing their applications to real-world meshes which
      often contain rich geometric details and/or various types of defects, such as
      noise and gaps. In order to increase the robustness of SDF and promote it to a
      wide range of 3D models, we define SDF by offsetting the input object a little
      bit. This seemingly minor change brings three significant benefits: First, it
      allows us to compute SDF in a robust manner since the offset surface is able to
      give reliable normal vectors. Second, it runs many times faster since at each
      point we only need to compute the penetration distance along a single direction,
      rather than tens of directions. Third, our method does not require watertight
      surfaces as the input-it supports both point clouds and meshes with noise and
      gaps. Extensive experimental results show that the offset-surface based SDF is
      robust to noise and insensitive to geometric details, and it also runs about 10
      times faster than the existing method. We also exhibit its usefulness using two
      typical applications including shape retrieval and shape segmentation, and
      observe a significant improvement over the existing SDF.

PMID- 29373579
TI  - An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2
      to the plasma membrane of renal collecting duct principal cells.
AB  - Stimulation of renal collecting duct principal cells with antidiuretic hormone
      (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and
      the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane.
      The membrane insertion facilitates water reabsorption from primary urine and fine
      tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs)
      interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the
      GTPase. However, GEFs involved in the control of AQP2 in renal principal cells
      are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity,
      specifically activates RhoA, and is expressed in primary renal inner medullary
      collecting duct principal (IMCD) cells. Through screening of 18,431 small
      molecules and synthesis of a focused library around one of the hits, we
      identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule,
      Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did
      not interfere with RhoA activation through other GEFs or activities of other
      members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted
      the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD
      cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA
      activation in the control of AQP2 trafficking.

PMID- 29373581
TI  - MUMmer4: A fast and versatile genome alignment system.
AB  - The MUMmer system and the genome sequence aligner nucmer included within it are
      among the most widely used alignment packages in genomics. Since the last major
      release of MUMmer version 3 in 2004, it has been applied to many types of
      problems including aligning whole genome sequences, aligning reads to a reference
      genome, and comparing different assemblies of the same genome. Despite its broad
      utility, MUMmer3 has limitations that can make it difficult to use for large
      genomes and for the very large sequence data sets that are common today. In this
      paper we describe MUMmer4, a substantially improved version of MUMmer that
      addresses genome size constraints by changing the 32-bit suffix tree data
      structure at the core of MUMmer to a 48-bit suffix array, and that offers
      improved speed through parallel processing of input query sequences. With a
      theoretical limit on the input size of 141Tbp, MUMmer4 can now work with input
      sequences of any biologically realistic length. We show that as a result of these
      enhancements, the nucmer program in MUMmer4 is easily able to handle alignments
      of large genomes; we illustrate this with an alignment of the human and
      chimpanzee genomes, which allows us to compute that the two species are 98%
      identical across 96% of their length. With the enhancements described here,
      MUMmer4 can also be used to efficiently align reads to reference genomes,
      although it is less sensitive and accurate than the dedicated read aligners. The
      nucmer aligner in MUMmer4 can now be called from scripting languages such as
      Perl, Python and Ruby. These improvements make MUMer4 one the most versatile
      genome alignment packages available.

PMID- 29373582
TI  - Vitrectomy without prone positioning for rhegmatogenous retinal detachments in
      eyes with inferior retinal breaks.
AB  - PURPOSE: To compare the anatomic and functional outcomes of pars plana vitrectomy
      (PPV) for treating rhegmatogenous retinal detachments (RRDs) between two groups
      with and without postoperative prone positioning. METHODS: This retrospective
      cohort study included 142 eyes of 142 patients with a primary RRD. All patients
      underwent PPV with 20% sulfur hexafluoride gas tamponade and were divided into
      two groups: the groups that did and did not maintain a prone position
      postoperatively. All patients were followed for more than 3 months. The main
      outcome measures were the best-corrected visual acuity (BCVA), retinal
      reattachment rate, and postoperative complications. RESULTS: Sixty-five eyes were
      included in the prone position group and 77 eyes in the group without prone
      positioning; the respective initial reattachment rates were 83.1% and 96.1%, a
      difference that reach significance (p = 0.011). In the eyes with inferior breaks,
      the initial reattachment rate was 94.7% (18 eyes) without prone positioning,
      which was significantly (p = 0.036) better than the 60% (6 eyes) initial
      reattachment rate in the group with prone positioning. In the eyes without
      inferior breaks, there was no significant difference in the initial reattachment
      rates between the two groups. The BCVAs at the 3-month postoperative visit did
      not differ significantly between the two groups. An epiretinal membrane (ERM) was
      observed postoperatively in 10 (13.0%) eyes in the group without prone
      positioning; no ERMs were seen postoperatively in eyes in which the internal
      limiting membrane (ILM) was peeled during PPV. CONCLUSIONS: PPV without
      postoperative prone positioning is associated with a higher reattachment rate in
      eyes with a RRD, especially those with inferior retinal breaks. PPV with
      postoperative supine and lateral positioning might be beneficial to manage RRDs
      associated with inferior retinal breaks if ILM peeling is performed
      intraoperatively.

PMID- 29373583
TI  - Zinc stimulates glucose oxidation and glycemic control by modulating the insulin
      signaling pathway in human and mouse skeletal muscle cell lines.
AB  - Zinc is a metal ion that is an essential cell signaling molecule. Highlighting
      this, zinc is an insulin mimetic, activating cellular pathways that regulate
      cellular homeostasis and physiological responses. Previous studies have linked
      dysfunctional zinc signaling with several disease states including cancer,
      obesity, cardiovascular disease and type 2 diabetes. The present study evaluated
      the insulin-like effects of zinc on cell signaling molecules including tyrosine,
      PRSA40, Akt, ERK1/2, SHP-2, GSK-3beta and p38, and glucose oxidation in human and
      mouse skeletal muscle cells. Insulin and zinc independently led to the
      phosphorylation of these proteins over a 60-minute time course in both mouse and
      human skeletal muscle cells. Similarly, utilizing a protein array we identified
      that zinc could active the phosphorylation of p38, ERK1/2 and GSK-3B in human and
      ERK1/2 and GSK-3B in mouse skeletal muscle cells. Glucose oxidation assays were
      performed on skeletal muscle cells treated with insulin, zinc, or a combination
      of both and resulted in a significant induction of glucose consumption in mouse
      (p<0.01) and human (p<0.05) skeletal muscle cells when treated with zinc alone.
      Insulin, as expected, increased glucose oxidation in mouse (p<0.001) and human
      (0.001) skeletal muscle cells, however the combination of zinc and insulin did
      not augment glucose consumption in these cells. Zinc acts as an insulin mimetic,
      activating key molecules implicated in cell signaling to maintain glucose
      homeostasis in mouse and human skeletal muscle cells. Zinc is an important metal
      ion implicated in several biological processes. The role of zinc as an insulin
      memetic in activating key signaling molecules involved in glucose homeostasis
      could provide opportunities to utilize this ion therapeutically in treating
      disorders associated with dysfunctional zinc signaling.

PMID- 29373584
TI  - Epigallocatechin-3-gallate confers protection against corticosterone-induced
      neuron injuries via restoring extracellular signal-regulated kinase 1/2 and
      phosphatidylinositol-3 kinase/protein kinase B signaling pathways.
AB  - Extensive studies suggested epigallocatechin-3-gallate (EGCG) has significant
      neuroprotection against multiple central neural injuries, but the underlying
      mechanisms still remain poorly elucidated. Here we provide evidence to support
      the possible involvement of extracellular signal-regulated kinase 1/2 (ERK1/2)
      and phosphatidylinositol-3 kinase/ protein kinase B (PI3K/AKT) pathways in EGCG
      mediated protection against corticosterone-induced neuron injuries. As an
      essential stress hormone, corticosterone could induce obvious neurotoxicity in
      primary hippocampal neurons. Pre-treatment with EGCG ameliorated the
      corticosterone-induced neuronal injuries; however, it was blocked by
      pharmacological inhibitors for ERK1/2 (U0126) and PI3K/AKT (LY294002).
      Furthermore, the results confirmed that EGCG restored the corticosterone-induced
      decrease of ERK1/2 and PI3K/AKT phosphorylation, and attenuated the
      corticosterone-induced reduction of peroxisome proliferators-activated receptor
      gamma coactivator-1alpha (PGC-1alpha) expression and ATP production. Taken
      together, these findings indicated that EGCG has significant neuroprotection
      against corticosterone-induced neuron injuries partly via restoring the ERK1/2
      and PI3K/AKT signaling pathways as well as the PGC-1alpha-mediated ATP
      production.

PMID- 29373585
TI  - Implication of molecular vascular smooth muscle cell heterogeneity among arterial
      beds in arterial calcification.
AB  - Vascular calcification is a strong and independent predictive factor for
      cardiovascular complications and mortality. Our previous work identified
      important discrepancies in plaque composition and calcification types between
      carotid and femoral arteries. The objective of this study is to further
      characterize and understand the heterogeneity in vascular calcification among
      vascular beds, and to identify molecular mechanisms underlying this process. We
      established ECLAGEN biocollection that encompasses human atherosclerotic lesions
      and healthy arteries from different locations (abdominal, thoracic aorta,
      carotid, femoral, and infrapopliteal arteries) for histological, cell isolation,
      and transcriptomic analysis. Our results show that lesion composition differs
      between these locations. Femoral arteries are the most calcified arteries
      overall. They develop denser calcifications (sheet-like, nodule), and are highly
      susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic
      differences between SMCs originating from these locations, as microarray analysis
      showed specific transcriptomic profiles between primary SMCs isolated from each
      arterial bed. These molecular differences translated into functional disparities.
      SMC from femoral arteries showed the highest propensity to mineralize due to an
      increase in basal TGFbeta signaling. Our results suggest that biological
      heterogeneity of resident vascular cells between arterial beds, reflected by our
      transcriptomic analysis, is critical in understanding plaque biology and
      calcification, and may have strong implications in vascular therapeutic
      approaches.

PMID- 29373586
TI  - Developmental profiling of microRNAs in the human embryonic inner ear.
AB  - Due to the extreme inaccessibility of fetal human inner ear tissue, defining of
      the microRNAs (miRNAs) that regulate development of the inner ear has relied on
      animal tissue. In the present study, we performed the first miRNA sequencing of
      otic precursors in human specimens. Using HTG miRNA Whole Transcriptome assays,
      we examined miRNA expression in the cochleovestibular ganglion (CVG), neural
      crest (NC), and otic vesicle (OV) from paraffin embedded (FFPE) human specimens
      in the Carnegie developmental stages 13-15. We found that in human embryonic
      tissues, there are different patterns of miRNA expression in the CVG, NC and OV.
      In particular, members of the miR-183 family (miR-96, miR-182, and miR-183) are
      differentially expressed in the CVG compared to NC and OV at Carnegie
      developmental stage 13. We further identified transcription factors that are
      differentially targeted in the CVG compared to the other tissues from stages 13
      15, and we performed gene set enrichment analyses to determine differentially
      regulated pathways that are relevant to CVG development in humans. These findings
      not only provide insight into the mechanisms governing the development of the
      human inner ear, but also identify potential signaling pathways for promoting
      regeneration of the spiral ganglion and other components of the inner ear.

PMID- 29373587
TI  - Qualitative analysis of the dynamics of policy design and implementation in
      hospital funding reform.
AB  - BACKGROUND: As in many health care systems, some Canadian jurisdictions have
      begun shifting away from global hospital budgets. Payment for episodes of care
      has begun to be implemented. Starting in 2012, the Province of Ontario
      implemented hospital funding reforms comprising three elements: Global Budgets;
      Health Based Allocation Method (HBAM); and Quality-Based Procedures (QBP). This
      evaluation focuses on implementation of QBPs, a procedure/diagnosis-specific
      funding approach involving a pre-set price per episode of care coupled with best
      practice clinical pathways. We examined whether or not there was consensus in
      understanding of the program theory underpinning QBPs and how this may have
      influenced full and effective implementation of this innovative funding model.
      METHODS: We undertook a formative evaluation of QBP implementation. We used an
      embedded case study method and in-depth, one-on-one, semi-structured, telephone
      interviews with key informants at three levels of the health care system:
      Designers (those who designed the QBP policy); Adoption Supporters (organizations
      and individuals supporting adoption of QBPs); and Hospital Implementers (those
      responsible for QBP implementation in hospitals). Thematic analysis involved an
      inductive approach, incorporating Framework analysis to generate descriptive and
      explanatory themes that emerged from the data. RESULTS: Five main findings
      emerged from our research: (1) Unbeknownst to most key informants, there was
      neither consistency nor clarity over time among QBP designers in their
      understanding of the original goal(s) for hospital funding reform; (2) Prior to
      implementation, the intended hospital funding mechanism transitioned from ABF to
      QBPs, but most key informants were either unaware of the transition or believe it
      was intentional; (3) Perception of the primary goal(s) of the policy reform
      continues to vary within and across all levels of key informants; (4) Four years
      into implementation, the QBP funding mechanism remains misunderstood; and (5)
      Ongoing differences in understanding of QBP goals and funding mechanism have
      created challenges with implementation and difficulties in measuring success.
      CONCLUSIONS: Policy drift and policy layering affected both the goal and the
      mechanism of action of hospital funding reform. Lack of early specification in
      both policy goals and hospital funding mechanism exposed the reform to reactive
      changes that did not reflect initial intentions. Several challenges further
      exacerbated implementation of complex hospital funding reforms, including a
      prolonged implementation schedule, turnover of key staff, and inconsistent
      messaging over time. These factors altered the trajectory of the hospital funding
      reforms and created confusion amongst those responsible for implementation.
      Enacting changes to hospital funding policy through a process that is
      transparent, collaborative, and intentional may increase the likelihood of
      achieving intended effects.

PMID- 29373588
TI  - Subsequent somatic axis and bone tissue metabolism responses to a low-zinc diet
      with or without phytase inclusion in broiler chickens.
AB  - Zinc is required for normal bone development and cartilage formation. The purpose
      of this study was to assess the effect of with adding organic Zn (alone or
      phytase inclusion) at the reduced dose to growing male Ross 308 chickens on
      somatic axis and bone tissue metabolism. 200 one-day old broilers were divided
      into the negative control group fed diet without Zn or phytase inclusion,
      positive control group receiving Zn in the 100% of daily recommended dose from
      ZnO, and two experimental groups fed diet introduced Zn in 25% of daily
      recommendation as a glycine chelate (Zn-Gly) with or without phytase inclusion
      (500 FTU.kg-1). Supplemental organic Zn increased bone Zn and Mg content, serum
      IGF-1, growth hormone and leptin concentration. Additional phytase inclusion
      increased body weight gain, blood plasma Ca, Fe, Zn and osteocalcin concentration
      and tibia ash percentage when compared to the Zn-deprived control. Bone geometry,
      yield and ultimate strengths were enhanced in both organic Zn supplemented
      groups, and the overall mechanical strength parameters of bone were better in
      these groups than in the positive control group supplemented with standard dose
      of inorganic Zn. Also marked improvements in the thickness of articular and the
      growth plate cartilages as well as real bone volume and thickness of metaphyseal
      trabeculae were achieved in all broilers fed Zn-supplemented diet irrespective of
      phytase inclusion, however, the highest cancellous bone mass and the best
      trabecular structure were noted after ZnO supplementation. In concludion,
      although dietary organic Zn given to growing broilers in 25% of daily recommended
      dose improved general bone properties and mechanical strength, the obtained
      results do not allow to unambiguously state that organic Zn supplementation at
      this level, even after phytase inclusion, is sufficient for proper bone
      development.

PMID- 29373589
TI  - Sensorimotor adaptation of voice fundamental frequency in Parkinson's disease.
AB  - OBJECTIVE: This study examined adaptive responses to auditory perturbation of
      fundamental frequency (fo) in speakers with Parkinson's disease (PD) and control
      speakers. METHOD: Sixteen speakers with PD and nineteen control speakers produced
      sustained vowels while they received perturbed auditory feedback (i.e., fo
      shifted upward or downward). Speakers' pitch acuity was quantified using a just
      noticeable-difference (JND) paradigm. Twelve listeners provided estimates of the
      speech intelligibility for speakers with PD. RESULTS: Fifteen responses from each
      speaker group for each shift direction were included in analyses. While control
      speakers generally showed consistent adaptive responses opposing the
      perturbation, speakers with PD showed no compensation on average, with individual
      PD speakers showing highly variable responses. In the PD group, the degree of
      compensation was not significantly correlated with age, disease progression,
      pitch acuity, or intelligibility. CONCLUSIONS: These findings indicate reduced
      adaptation to sustained fo perturbation and higher variability in PD compared to
      control participants. No significant differences were seen in pitch acuity
      between groups, suggesting that the fo adaptation deficit in PD is not the result
      of purely perceptual mechanisms. SIGNIFICANCE: These results suggest there is an
      impairment in vocal motor control in PD. Building on these results, contributions
      can be made to developing targeted voice treatments for PD.

PMID- 29373590
TI  - Risk preferences impose a hidden distortion on measures of choice impulsivity.
AB  - Measuring temporal discounting through the use of intertemporal choice tasks is
      now the gold standard method for quantifying human choice impulsivity
      (impatience) in neuroscience, psychology, behavioral economics, public health and
      computational psychiatry. A recent area of growing interest is individual
      differences in discounting levels, as these may predispose to (or protect from)
      mental health disorders, addictive behaviors, and other diseases. At the same
      time, more and more studies have been dedicated to the quantification of
      individual attitudes towards risk, which have been measured in many clinical and
      non-clinical populations using closely related techniques. Economists have
      pointed to interactions between measurements of time preferences and risk
      preferences that may distort estimations of the discount rate. However, although
      becoming standard practice in economics, discount rates and risk preferences are
      rarely measured simultaneously in the same subjects in other fields, and the
      magnitude of the imposed distortion is unknown in the assessment of individual
      differences. Here, we show that standard models of temporal discounting -such as
      a hyperbolic discounting model widely present in the literature which fails to
      account for risk attitudes in the estimation of discount rates- result in a large
      and systematic pattern of bias in estimated discounting parameters. This can lead
      to the spurious attribution of differences in impulsivity between individuals
      when in fact differences in risk attitudes account for observed behavioral
      differences. We advance a model which, when applied to standard choice tasks
      typically used in psychology and neuroscience, provides both a better fit to the
      data and successfully de-correlates risk and impulsivity parameters. This results
      in measures that are more accurate and thus of greater utility to the many fields
      interested in individual differences in impulsivity.

PMID- 29373591
TI  - A trivalent Apx-fusion protein delivered by E. coli outer membrane vesicles
      induce protection against Actinobacillus pleuropneumoniae of serotype 1 and 7
      challenge in a murine model.
AB  - Actinobacillus pleuropneumoniae (APP) causes serious economic losses in the swine
      industry, and is the etiologic agent of porcine pleuropneumonia. In this study we
      have engineered a trivalent Apx fusion protein enclosed in outer membrane
      vesicles (Apxr-OMV) and studied its immunoprotective efficacy against APP
      serotypes 1 and 7 challenge in mice. The results showed that the IgG levels in
      the Apxr-OMVs immune group were significantly higher than those of the negative
      control (P < 0.05). Up-regulation of both Th1 (IFN-gamma, IL-2) and Th2 (IL-4)
      cytokines were detected in splenocytes of Apxr-OMVs immune group. The survival
      rates 87.5% and 62.5% were observed against APP strain 1516 of serotype 7 and APP
      strain 2701 of serotype 1 in the groups of Apxr-OMVs immune group, respectively.
      Histopathological lesions of the pulmonary structure alveoli were found to be
      minimal in APX-OMV group challenged with APP serotypes 1 and 7. These results
      strongly indicated that engineered OMVs could effectively induce specific humoral
      or cellular immune responses. Moreover, Apxr-OMVs used as novel vaccine provides
      cross-protective immunity against different serotype 1 and 7 of APP infection in
      a mouse model. In contrast, the OMV-empty and PBS as negative controls or
      inactivated strain of APP-2701 and APP-1516 as positive controls for the animal
      study cannot provide protection or cross-protection.

PMID- 29373592
TI  - Strontium isotopes reveal weathering processes in lateritic covers in southern
      China with implications for paleogeographic reconstructions.
AB  - The isotope ratios of Sr are useful tracers for studying parent material sources,
      weathering processes, and biogeochemical cycling. Mineralogical and geochemical
      investigations of two lateritic weathering covers, in an area close to the Tropic
      of Cancer (Guangxi Province, southern China), were undertaken to study the
      regional weathering processes and Sr isotopic sources. We found that weathering
      and decomposition of Rb- and Sr-bearing minerals change the Sr isotopic
      composition in weathering products (lateritic soils). Weathering of illite
      lowered the 87Sr/86Sr ratio whereas dissolving and leaching of carbonate minerals
      increased the 87Sr/86Sr ratio. An Fe nodular horizon is widely developed on the
      top of the weathering covers in the studied area and it differs from the
      lateritic soil horizon in mineral composition, construction, and elemental
      concentration. Furthermore, both Fe2O3 and P2O5 (concentrations) are negatively
      correlated with the 87Sr/86Sr ratios, suggesting fixation of apatite by Fe oxides
      is a controlling factor of the Sr isotopic composition in the Fe nodular horizon.
      The 87Sr/86Sr and Nb/Sr ratios imply the contents and proportions of Fe nodules
      and clay are critical in controlling the changes of Sr isotopic composition in
      the Fe nodular horizon. The two stages of the weathering process of carbonate
      rocks are revealed by the87Sr/86Sr versus Nb/Sr diagram. The 87Sr/86Sr and Rb/Sr
      ratios suggest that Sr isotopes in the weathering covers within the studied area
      are derived mainly from parent rock weathering and that the contributions from
      allothogenic Sr isotopes are limited. A comparison of Sr isotopic composition
      signatures in the weathering covers of the studied area and Guizhou Province
      provided insight into the Sr isotopic source and paleogeographic evolution of
      southern China. From the Permian to the Triassic, the continental fragment
      sources of the South China sedimentary basin changed significantly. In the
      Permian, Southern China presented the paleogeographic pattern that the north was
      higher (in elevation) than the south.

PMID- 29373593
TI  - Laying sequence interacts with incubation temperature to influence rate of
      embryonic development and hatching synchrony in a precocial bird.
AB  - Incubation starts during egg laying for many bird species and causes
      developmental asynchrony within clutches. Faster development of late-laid eggs
      can help reduce developmental differences and synchronize hatching, which is
      important for precocial species whose young must leave the nest soon after
      hatching. In this study, we examined the effect of egg laying sequence on length
      of the incubation period in Wood Ducks (Aix sponsa). Because incubation
      temperature strongly influences embryonic development rates, we tested the
      interactive effects of laying sequence and incubation temperature on the ability
      of late-laid eggs to accelerate development and synchronize hatching. We also
      examined the potential cost of faster development on duckling body condition.
      Fresh eggs were collected and incubated at three biologically relevant
      temperatures (Low: 34.9 degrees C, Medium: 35.8 degrees C, and High: 37.6 degrees
      C), and egg laying sequences from 1 to 12 were used. Length of the incubation
      period declined linearly as laying sequence advanced, but the relationship was
      strongest at medium temperatures followed by low temperatures and high
      temperatures. There was little support for including fresh egg mass in models of
      incubation period. Estimated differences in length of the incubation period
      between eggs 1 and 12 were 2.7 d, 1.2 d, and 0.7 d at medium, low and high
      temperatures, respectively. Only at intermediate incubation temperatures did
      development rates of late-laid eggs increase sufficiently to completely
      compensate for natural levels of developmental asynchrony that have been reported
      in Wood Duck clutches at the start of full incubation. Body condition of
      ducklings was strongly affected by fresh egg mass and incubation temperature but
      declined only slightly as laying sequence progressed. Our findings show that
      laying sequence and incubation temperature play important roles in helping to
      shape embryo development and hatching synchrony in a precocial bird.

PMID- 29373594
TI  - Biofilm formation and transcriptome analysis of Streptococcus gallolyticus subsp.
      gallolyticus in response to lysozyme.
AB  - Streptococcus gallolyticus subsp. gallolyticus is a commensal bacterium of the
      human gastrointestinal tract, and a pathogen causing infective endocarditis and
      other biofilm-associated infections via exposed collagen. This study focuses on
      the characterization of the biofilm formation and collagen adhesion of S.
      gallolyticus subsp. gallolyticus under different conditions. In this study, it
      has been observed that the isolate UCN 34 is resistant to 20 mg/ml lysozyme in
      BHI medium, whereas the strain BAA-2069 builds more biofilm in the presence of
      lysozyme compared to in a control of BHI without lysozyme. A transcriptome
      analysis with whole genome microarrays of these two isolates in BHI medium with
      lysozyme compared to control without lysozyme revealed changes in gene expression
      levels. In the isolate BAA-2069, 67 genes showed increased expression in the
      presence of lysozyme, while in the isolate UCN 34, 165 genes showed increased
      expression and 30 genes showed decreased expression through lysozyme treatment.
      Products of genes which were higher expressed are in involved in transcription
      and translation, in cell-wall modification, in hydrogen peroxide resistance and
      in bacterial immunity. Furthermore, the adhesion ability of different strains of
      S. gallolyticus subsp. gallolyticus to collagen type I and IV was analyzed.
      Thereby, we compared the adhesion of 46 human isolates with 23 isolates from
      animals. It was shown that the adhesion ability depends significantly on whether
      the isolate was isolated from human or animal. For example, high adhesion ability
      was observed for strain UCN 34 isolated from an infective endocarditis patient,
      whereas strain DSM 16831 isolated from koala feces adhered only marginally to
      collagen. Full genome microarray analysis of these two strains revealed strain
      dependent gene expression due to adhesion. The expression of 25 genes of a
      transposon and 15 genes of a phage region in strain DSM 16831 were increased,
      which corresponds to horizontal gene transfer. Adherence to collagen in strain
      UCN 34 led to higher expression of 27 genes and lower expression of 31 genes.
      This was suggestive of a change in nutrient uptake.

PMID- 29373595
TI  - Hospitalizations due to unintentional transport injuries among Aboriginal
      population of British Columbia, Canada: Incidence, changes over time and
      ecological analysis of risk markers.
AB  - BACKGROUND: Worldwide, Indigenous people have disproportionately higher rates of
      transport injuries. We examined disparities in injury-related hospitalizations
      resulting from transport incidents for three population groups in British
      Columbia (BC): total population, Aboriginal off-reserve, and Aboriginal on
      reserve populations. We also examined sociodemographic, geographic and ethnic
      risk markers for disparities. METHODS: We identified Aboriginal people through
      BC's universal health care insurance plan insurance premium group and birth and
      death record notations. We calculated crude incidence rate and Standardized
      Relative Risk (SRR) of hospitalization for unintentional transport injury,
      standardized for age, gender and Health Service Delivery Area (HSDA), relative to
      the total population of BC. We tested hypothesized associations of geographic,
      socio-economic, and employment-related characteristics of Aboriginal communities
      with SRR of transport injury by multivariable linear regression. RESULTS: During
      the period 1991-2010, the SRR for the off-reserve Aboriginal population was 1.77
      (95% CI: 1.71 to 1.83); and 2.00 (95% CI: 1.93 to 2.07) among those living on
      reserve. Decline in crude rate and SRRs was observed over this period among both
      the Aboriginal and total populations of BC, but was proportionally greater among
      the Aboriginal population. The best-fitting multivariable risk marker model was
      an excellent fit (R2 = 0.912, p<0.001), predicted SRRs very close to observed
      values, and retained the following terms: urban residence, population per room,
      proportion of the population with a high school certificate, proportion of the
      population employed; and multiplicative interactions of Aboriginal ethnicity with
      population per room and proportion of the population employed. CONCLUSIONS:
      Disparities in risk of hospitalization due to unintentional transport injury have
      narrowed. Aboriginal ethnicity modifies the effects of socioeconomic risk
      factors. Continued improvement of socioeconomic conditions and implementation of
      culturally relevant injury prevention interventions are needed.

PMID- 29373597
TI  - High dietary zinc feeding promotes persistence of multi-resistant E. coli in the
      swine gut.
AB  - High levels of zinc oxide are used frequently as feed additive in pigs to improve
      gut health and growth performance and are still suggested as an alternative to
      antimicrobial growth promoters. However, we have recently described an increase
      of multi-resistant E. coli in association to zinc feeding in piglets. This
      previous study focused on clonal diversity of E. coli, observing the effect on
      multi-resistant strains by chance. To shed further light into this highly
      important topic and falsify our previous findings, we performed a zinc pig
      feeding trial where we specifically focused on in-depth analysis of antimicrobial
      resistant E. coli. Under controlled experimental conditions, piglets were
      randomly allocated to a high dietary zinc (zinc group) and a background zinc
      feeding group (control group). At different ages samples were taken from feces,
      digesta, and mucosa and absolute E. coli numbers were determined. A total of 2665
      E. coli isolates were than phenotypically tested for antimicrobial resistance and
      results were confirmed by minimum inhibitory concentration testing for random
      samples. In piglets fed with high dietary zinc, we detected a substantial
      increase of multi-resistant E. coli in all gut habitats tested, ranging from 28.9
      30.2% multi-resistant E. coli compared to 5.8-14.0% in the control group. This
      increase was independent of the total number of E. coli. Interestingly, the total
      amount of the E. coli population decreased over time. Thus, the increase of the
      multi-resistant E. coli populations seems to be linked with persistence of the
      resistant population, caused by the influence of high dietary zinc feeding. In
      conclusion, these findings corroborate our previous report linking high dietary
      zinc feeding of piglets with the occurrence of antimicrobial resistant E. coli
      and therefore question the feeding of high dietary zinc oxide as alternative to
      antimicrobial growth promoters.

PMID- 29373596
TI  - Increasingly inbred and fragmented populations of Plasmodium vivax associated
      with the eastward decline in malaria transmission across the Southwest Pacific.
AB  - The human malaria parasite Plasmodium vivax is more resistant to malaria control
      strategies than Plasmodium falciparum, and maintains high genetic diversity even
      when transmission is low. To investigate whether declining P. vivax transmission
      leads to increasing population structure that would facilitate elimination, we
      genotyped samples from across the Southwest Pacific region, which experiences an
      eastward decline in malaria transmission, as well as samples from two time points
      at one site (Tetere, Solomon Islands) during intensified malaria control.
      Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New
      Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and
      hypoendemic Vanuatu (n = 24) revealed increasing population structure and
      multilocus linkage disequilibrium yet a modest decline in diversity as
      transmission decreases over space and time. In Solomon Islands, which has had
      sustained control efforts for 20 years, and Vanuatu, which has experienced
      sustained low transmission for many years, significant population structure was
      observed at different spatial scales. We conclude that control efforts will
      eventually impact P. vivax population structure and with sustained pressure,
      populations may eventually fragment into a limited number of clustered foci that
      could be targeted for elimination.

PMID- 29373598
TI  - Quantitative characterization of viscoelastic behavior in tissue-mimicking
      phantoms and ex vivo animal tissues.
AB  - Viscoelasticity of soft tissue is often related to pathology, and therefore, has
      become an important diagnostic indicator in the clinical assessment of suspect
      tissue. Surgeons, particularly within head and neck subsites, typically use
      palpation techniques for intra-operative tumor detection. This detection method,
      however, is highly subjective and often fails to detect small or deep
      abnormalities. Vibroacoustography (VA) and similar methods have previously been
      used to distinguish tissue with high-contrast, but a firm understanding of the
      main contrast mechanism has yet to be verified. The contributions of tissue
      mechanical properties in VA images have been difficult to verify given the
      limited literature on viscoelastic properties of various normal and diseased
      tissue. This paper aims to investigate viscoelasticity theory and present a
      detailed description of viscoelastic experimental results obtained in tissue
      mimicking phantoms (TMPs) and ex vivo tissues to verify the main contrast
      mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation
      technique was employed with the Hertzian model to acquire absolute, quantitative,
      point measurements of the elastic modulus (E), long term shear modulus (eta), and
      time constant (tau) in homogeneous TMPs and ex vivo tissue in rat liver and
      porcine liver and gallbladder. Viscoelastic differences observed between porcine
      liver and gallbladder tissue suggest that imaging modalities which utilize the
      mechanical properties of tissue as a primary contrast mechanism can potentially
      be used to quantitatively differentiate between proximate organs in a clinical
      setting. These results may facilitate more accurate tissue modeling and add
      information not currently available to the field of systems characterization and
      biomedical research.

PMID- 29373599
TI  - Drug drug interaction extraction from the literature using a recursive neural
      network.
AB  - Detecting drug-drug interactions (DDI) is important because information on DDIs
      can help prevent adverse effects from drug combinations. Since there are many new
      DDI-related papers published in the biomedical domain, manually extracting DDI
      information from the literature is a laborious task. However, text mining can be
      used to find DDIs in the biomedical literature. Among the recently developed
      neural networks, we use a Recursive Neural Network to improve the performance of
      DDI extraction. Our recursive neural network model uses a position feature, a
      subtree containment feature, and an ensemble method to improve the performance of
      DDI extraction. Compared with the state-of-the-art models, the DDI detection and
      type classifiers of our model performed 4.4% and 2.8% better, respectively, on
      the DDIExtraction Challenge'13 test data. We also validated our model on the PK
      DDI corpus that consists of two types of DDIs data: in vivo DDI and in vitro DDI.
      Compared with the existing model, our detection classifier performed 2.3% and
      6.7% better on in vivo and in vitro data respectively. The results of our
      validation demonstrate that our model can automatically extract DDIs better than
      existing models.

PMID- 29373600
TI  - Schistosoma mansoni infection suppresses the growth of Plasmodium yoelii
      parasites in the liver and reduces gametocyte infectivity to mosquitoes.
AB  - Malaria and schistosomiasis are major parasitic diseases causing morbidity and
      mortality in the tropics. Epidemiological surveys have revealed coinfection rates
      of up to 30% among children in Sub-Saharan Africa. To investigate the impact of
      coinfection of these two parasites on disease epidemiology and pathology, we
      carried out coinfection studies using Plasmodium yoelii and Schistosoma mansoni
      in mice. Malaria parasite growth in the liver following sporozoite inoculation is
      significantly inhibited in mice infected with S. mansoni, so that when low
      numbers of sporozoites are inoculated, there is a large reduction in the
      percentage of mice that go on to develop blood stage malaria. Furthermore,
      gametocyte infectivity is much reduced in mice with S. mansoni infections. These
      results have profound implications for understanding the interactions between
      Plasmodium and Schistosoma species, and have implications for the control of
      malaria in schistosome endemic areas.

PMID- 29373601
TI  - Transcriptional changes detected in fecal RNA of neonatal dairy calves undergoing
      a mild diarrhea are associated with inflammatory biomarkers.
AB  - After birth, a newborn calf has to adapt to an extrauterine life characterized by
      several physiological changes. In particular, maturation of the gastrointestinal
      tract in a new environment loaded with potential pathogens, which can predispose
      neonatal calves to develop diarrhea, and is a major cause of morbidity and
      mortality during the first 4 wks of life. We aimed to investigate the
      inflammatory adaptations at a transcriptomic level in the gastrointestinal (GI)
      tract to a mild diarrhea in neonatal dairy calves using RNA isolated from fresh
      fecal samples. Eight newborn Jersey male calves were used from birth to 5 wks of
      age and housed in individual pens. After birth, calves received 1.9 L of
      colostrum from their respective dams. Calves had ad-libitum access to water and
      starter grain (22% CP) and were fed twice daily a total of 5.6 L pasteurized
      whole milk. Starter intake, body weight (BW), fecal score, withers height (WH),
      and rectal temperature (RT) were recorded throughout the experiment. Blood
      samples were collected weekly for metabolic and inflammatory profiling from wk 0
      to wk 5. Fresh fecal samples were collected weekly and immediately flash frozen
      until RNA was extracted using a Trizol-based method, and subsequently, an RT-qPCR
      analysis was performed. Orthogonal contrasts were used to evaluate linear or
      quadratic effects over time. Starter intake, BW, and WH increased over time.
      Fecal score was greatest (2.6 +/- 0.3) during wk 2. The concentrations of IL-6,
      ceruloplasmin, and haptoglobin had a positive quadratic effect with maximal
      concentrations during wk 2, which corresponded to the maximal fecal score
      observed during the same time. The concentration of serum amyloid A decreased
      over time. The mRNA expression of the proinflammatory related genes TLR4, TNFA,
      IL8, and IL1B had a positive quadratic effect of time. A time effect was observed
      for the cell membrane sodium-dependent glucose transporter SLC5A1, for the major
      carbohydrate facilitated transporter SLC2A2, and water transport function AQP3,
      where SLC5A1 and AQP3 had a negative quadratic effect over time. Our data support
      the use of the fecal RNA as a noninvasive tool to investigate intestinal
      transcriptomic profiling of dairy calves experiencing diarrhea, which would be
      advantageous for future research including nutritional effects and health
      conditions.

PMID- 29373602
TI  - Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in
      nonvalvular atrial fibrillation patients: Comparative effectiveness and safety
      evaluated using a propensity-score-matched approach.
AB  - : Prior real-world studies have shown that apixaban is associated with a reduced
      risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin.
      However, few studies evaluated the effectiveness and safety of apixaban according
      to its dosage, and most studies contained limited numbers of patients prescribed
      2.5 mg twice-daily (BID) apixaban. Using pooled data from 4 American claims
      database sources, baseline characteristics and outcomes for patients prescribed 5
      mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1
      propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and
      6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients
      prescribed 2.5 mg BID apixaban were older, had clinically more severe
      comorbidities, and were more likely to have a history of stroke and bleeding
      compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID
      apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70,
      95% confidence interval [CI]: 0.60-0.81) and major bleeding (HR: 0.59, 95% CI:
      0.53-0.66). Compared with warfarin, 2.5 mg BID apixaban was also associated with
      a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49-0.81) and major bleeding (HR:
      0.59, 95% CI: 0.49-0.71). In this real-world study, both apixaban doses were
      assessed in 2 patient groups differing in age and clinical characteristics. Each
      apixaban dose was associated with a lower risk of stroke/SE and major bleeding
      compared with warfarin in the distinct population for which it is being
      prescribed in United States clinical practice. TRIAL REGISTRATION:
      Clinicaltrials.Gov Identifier: NCT03087487.

PMID- 29373603
TI  - N-acetylcysteine alleviates cadmium-induced placental endoplasmic reticulum
      stress and fetal growth restriction in mice.
AB  - Cadmium (Cd) is a developmental toxicant that induces fetal growth restriction
      (FGR). Placental endoplasmic reticulum (ER) stress is associated with FGR. This
      study investigated the effects of N-acetylcysteine (NAC) on Cd-induced placental
      ER stress and FGR. Pregnant mice were intraperitoneally injected with CdCl2 daily
      from gestational day (GD)13 to GD17. As expected, Cd reduced fetal weight and
      crown-rump length. Cd decreased the internal space of blood vessels in the
      placental labyrinth layer and inhibited placental cell proliferation. Several
      genes of growth factors, such as Vegf-a, placental growth factor, Igf1 and Igf1r,
      and several genes of nutrient transport pumps, such as Glut1, Fatp1 and Snat2,
      were down-regulated in placenta of Cd-treated mice. Moreover, Cd evoked placental
      ER stress. Of interest, NAC alleviated Cd-induced FGR. Additional experiment
      showed that NAC inhibited Cd-induced impairment of placental development and
      placental ER stress. Therefore, NAC may be exploited for prevention of Cd-induced
      placental insufficiency and FGR.

PMID- 29373604
TI  - Excessive scleral shrinkage, rather than choroidal thickening, is a major
      contributor to the development of hypotony maculopathy after trabeculectomy.
AB  - PURPOSE: We previously reported that eyes with hypotony maculopathy (HM) after
      trabeculectomy (TLE) exhibited more reduction of axial length (AL) than those
      without HM, suggesting that inward collapse of the scleral wall may contribute to
      the development of HM after TLE. However, we did not evaluate change in choroidal
      thickness (CT), which could influence AL measures. We compared the magnitude and
      rate of AL and CT changes in eyes with and without HM by simultaneously measuring
      these parameters before and after TLE. METHODS: We enrolled 77 eyes of
      77consecutive patients with glaucoma, who underwent TLE between March 2014 and
      March 2016. Intraocular pressure (IOP), central corneal thickness, keratometry,
      AL, and CT were measured pre- and postoperatively, up to 6 months. These
      biometrics were compared in eyes with and without HM. RESULTS: The 14 patients
      who developed HM were significantly younger than those who did not. The eyes with
      HM exhibited significantly reduced AL (2.8%) compared to those without HM (0.7%).
      There was no significant difference in CT change between the two groups. The rate
      of AL reduction was significantly correlated with age, postoperative IOP, and
      preoperative AL. Post-adjustment logistic regression analysis revealed that eyes
      with AL reduction rate >= 2% had 11.67 higher risk for developing HM (95%
      confidence interval, 1.28-106.6; P = 0.03). CONCLUSIONS: AL reduction rates >= 2%
      were significantly associated with HM. Excessive reduction in AL, which was seen
      in eyes with HM, was not an artificial measure resulting from choroidal
      thickening but rather reflected reductions in the anterior-posterior diameter of
      the eyeball. Inward collapse of the scleral wall leads to redundancy of the
      chorioretinal tissue, contributing to the development of HM after TLE.

PMID- 29373605
TI  - Plant identity and shallow soil moisture are primary drivers of stomatal
      conductance in the savannas of Kruger National Park.
AB  - Our goal was to describe stomatal conductance (gs) and the site-scale
      environmental parameters that best predict gs in Kruger National Park (KNP),
      South Africa. Dominant grass and woody species were measured over two growing
      seasons in each of four study sites that represented the natural factorial
      combination of mean annual precipitation [wet (750 mm) or dry (450 mm)] and soil
      type (clay or sand) found in KNP. A machine-learning (random forest) model was
      used to describe gs as a function of plant type (species or functional group) and
      site-level environmental parameters (CO2, season, shortwave radiation, soil type,
      soil moisture, time of day, vapor pressure deficit and wind speed). The model
      explained 58% of the variance among 6,850 gs measurements. Species, or plant
      functional group, and shallow (0-20 cm) soil moisture had the greatest effect on
      gs. Atmospheric drivers and soil type were less important. When parameterized
      with three years of observed environmental data, the model estimated mean daytime
      growing season gs as 68 and 157 mmol m-2 sec-1 for grasses and woody plants,
      respectively. The model produced here could, for example, be used to estimate gs
      and evapotranspiration in KNP under varying climate conditions. Results from this
      field-based study highlight the role of species identity and shallow soil
      moisture as primary drivers of gs in savanna ecosystems of KNP.

PMID- 29373606
TI  - Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid
      hormones.
AB  - Significant sex specific differences in the progression of HIV/AIDS have been
      reported. Several studies have implicated steroid hormones in regulating host
      factor expression and modulating HIV transmission and replication. However, the
      exact mechanism exerted by steroid hormones estrogen and progesterone in the
      regulation of HIV-1 replication is still unclear. Results from the current study
      indicated a dose dependent down regulation of HIV-1 replication in monocyte
      derived macrophages pre-treated with high concentrations of estrogen or
      progesterone. To elucidate the molecular mechanisms associated with the down
      regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays
      to analyze the expression profile of host genes involved in antiviral responses.
      Several chemokines, cytokines, transcription factors, interferon stimulated genes
      and genes involved in type-1 interferon signaling were down regulated in cells
      infected with HIV-1 pre-treated with high concentrations of estrogen or
      progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells
      treated with low concentrations of estrogen or progesterone. The down regulation
      of CXCL9, CXCL10 and CXCL11 chemokines and IL-1beta, IL-6 cytokines in response
      to high concentrations of estrogen and progesterone pre-treatment in HIV-1
      infected cells was confirmed at the protein level by quantitating chemokine and
      cytokine concentrations in the culture supernatant. These results demonstrate
      that a potent anti-inflammatory response is mediated by pre-treatment with high
      concentrations of estrogen and progesterone. Thus, our study suggests a strong
      correlation between the down-modulation of anti-viral and pro-inflammatory
      responses mediated by estrogen and progesterone pre-treatment and the down
      regulation of HIV-1 replication. These findings may be relevant to clinical
      observations of sex specific differences in patient populations and point to the
      need for further investigation.

PMID- 29373607
TI  - Editing of the human TRIM5 gene to introduce mutations with the potential to
      inhibit HIV-1.
AB  - The type I interferon (IFN-I)-inducible human restriction factor TRIM5alpha
      inhibits the infection of human cells by specific nonhuman retroviruses, such as
      N-MLV and EIAV, but does not generally target HIV-1. However, the introduction of
      two aminoacid substitutions, R332G and R355G, in the human TRIM5alpha
      (huTRIM5alpha) domain responsible for retroviral capsid recognition leads to
      efficient HIV-1 restriction upon stable over-expression. CRISPR-Cas-based
      approaches to precisely edit DNA could be employed to modify TRIM5 in human
      cells. Toward this aim, we used a DNA transfection-based CRISPR-Cas9 genome
      editing protocol to successfully mutate TRIM5 to its potentially HIV-1
      restrictive version by homology-directed repair (HDR) in HEK293T cells. Nine
      clones bearing at least one HDR-edited TRIM5 allele containing both mutations
      were isolated (5.6% overall efficiency), whereas another one contained only the
      R332G mutation. Of concern, several of these HDR-edited clones contained on
      target undesired mutations, and none had all the alleles corrected. Our study
      demonstrates the feasibility of editing the TRIM5 gene in human cells and
      identifies the main challenges to be addressed in order to use this approach to
      confer protection from HIV-1.

PMID- 29373608
TI  - Interleukin-33 induces interleukin-8 expression via JNK/c-Jun/AP-1 pathway in
      human umbilical vein endothelial cells.
AB  - Interleukin (IL)-33 is a member of the IL-1 cytokine family with dual functions
      as a traditional cytokine and as a transcriptional regulator. We recently
      reported that IL-33 up-regulated growth regulated oncogene (GRO)-alpha/CXCL1
      expression in human vascular endothelial cells. The aim of this study was to
      investigate the effect of IL-33 on the expression of IL-8/CXCL8, another member
      of the CXC-chemokine family, and to elucidate its signaling pathways in human
      umbilical vein endothelial cells (HUVECs). Immunocytochemical staining and
      Western immunoblot analysis revealed that IL-33 augmented IL-8 protein expression
      in HUVECs. Real time reverse transcription-polymerase chain reaction (RT-PCR) and
      enzyme-linked immunosorbent assay (ELISA) showed that IL-33 significantly
      increased IL-8 mRNA and secretion in a dose- and time-dependent manner. IL-33
      preferentially stimulated proliferating subconfluent cells, and increased IL-8
      secretion to a higher level compared with confluent cells. IL-33 also stimulated
      phosphorylations of c-Jun N-terminal kinase (JNK) and c-Jun, and enhanced
      activator protein (AP)-1 DNA-binding activity, all of which were suppressed by
      SP600125, a JNK inhibitor. Moreover, IL-33-induced IL-8 mRNA and secretion were
      also suppressed by SP600125. Transfection of c-Jun small interfering RNA into
      cultured HUVECs significantly reduced the IL-33-induced increase in IL-8
      secretion from HUVECs. The present study demonstrates that IL-33 induces IL-8
      expression via JNK/c-Jun/AP-1 pathway in human vascular endothelial cells, and
      provides a new insight into the role of IL-33-induced IL-8 in the pathophysiology
      of atherosclerosis and vascular inflammation.

PMID- 29373609
TI  - Systematic identification of latent disease-gene associations from PubMed
      articles.
AB  - Recent scientific advances have accumulated a tremendous amount of biomedical
      knowledge providing novel insights into the relationship between molecular and
      cellular processes and diseases. Literature mining is one of the commonly used
      methods to retrieve and extract information from scientific publications for
      understanding these associations. However, due to large data volume and
      complicated associations with noises, the interpretability of such association
      data for semantic knowledge discovery is challenging. In this study, we describe
      an integrative computational framework aiming to expedite the discovery of latent
      disease mechanisms by dissecting 146,245 disease-gene associations from over 25
      million of PubMed indexed articles. We take advantage of both Latent Dirichlet
      Allocation (LDA) modeling and network-based analysis for their capabilities of
      detecting latent associations and reducing noises for large volume data
      respectively. Our results demonstrate that (1) the LDA-based modeling is able to
      group similar diseases into disease topics; (2) the disease-specific association
      networks follow the scale-free network property; (3) certain subnetwork patterns
      were enriched in the disease-specific association networks; and (4) genes were
      enriched in topic-specific biological processes. Our approach offers promising
      opportunities for latent disease-gene knowledge discovery in biomedical research.

PMID- 29373612
TI  - Are meta-analyses clinically useful?

PMID- 29373610
TI  - Don't speak too fast! Processing of fast rate speech in children with specific
      language impairment.
AB  - BACKGROUND: Perception of speech rhythm requires the auditory system to track
      temporal envelope fluctuations, which carry syllabic and stress information.
      Reduced sensitivity to rhythmic acoustic cues has been evidenced in children with
      Specific Language Impairment (SLI), impeding syllabic parsing and speech
      decoding. Our study investigated whether these children experience specific
      difficulties processing fast rate speech as compared with typically developing
      (TD) children. METHOD: Sixteen French children with SLI (8-13 years old) with
      mainly expressive phonological disorders and with preserved comprehension and 16
      age-matched TD children performed a judgment task on sentences produced 1) at
      normal rate, 2) at fast rate or 3) time-compressed. Sensitivity index (d') to
      semantically incongruent sentence-final words was measured. RESULTS: Overall
      children with SLI perform significantly worse than TD children. Importantly, as
      revealed by the significant Group * Speech Rate interaction, children with SLI
      find it more challenging than TD children to process both naturally or
      artificially accelerated speech. The two groups do not significantly differ in
      normal rate speech processing. CONCLUSION: In agreement with rhythm-processing
      deficits in atypical language development, our results suggest that children with
      SLI face difficulties adjusting to rapid speech rate. These findings are
      interpreted in light of temporal sampling and prosodic phrasing frameworks and of
      oscillatory mechanisms underlying speech perception.

PMID- 29373611
TI  - Accuracy and reliability of noninvasive stroke volume monitoring via ECG-gated 3D
      electrical impedance tomography in healthy volunteers.
AB  - Cardiac output (CO) and stroke volume (SV) are parameters of key clinical
      interest. Many techniques exist to measure CO and SV, but are either invasive or
      insufficiently accurate in clinical settings. Electrical impedance tomography
      (EIT) has been suggested as a noninvasive measure of SV, but inconsistent results
      have been reported. Our goal is to determine the accuracy and reliability of EIT
      based SV measurements, and whether advanced image reconstruction approaches can
      help to improve the estimates. Data were collected on ten healthy volunteers
      undergoing postural changes and exercise. To overcome the sensitivity to heart
      displacement and thorax morphology reported in previous work, we used a 3D EIT
      configuration with 2 planes of 16 electrodes and subject-specific reconstruction
      models. Various EIT-derived SV estimates were compared to reference measurements
      derived from the oxygen uptake. Results revealed a dramatic impact of posture on
      the EIT images. Therefore, the analysis was restricted to measurements in supine
      position under controlled conditions (low noise and stable heart and lung
      regions). In these measurements, amplitudes of impedance changes in the heart and
      lung regions could successfully be derived from EIT using ECG gating. However,
      despite a subject-specific calibration the heart-related estimates showed an
      error of 0.0 +/- 15.2 mL for absolute SV estimation. For trending of relative SV
      changes, a concordance rate of 80.9% and an angular error of -1.0 +/- 23.0
      degrees  were obtained. These performances are insufficient for most clinical
      uses. Similar conclusions were derived from lung-related estimates. Our findings
      indicate that the key difficulty in EIT-based SV monitoring is that purely
      amplitude-based features are strongly influenced by other factors (such as
      posture, electrode contact impedance and lung or heart conductivity). All the
      data of the present study are made publicly available for further investigations.

PMID- 29373613
TI  - Passings to note: Paul Michael Packman, MD; S. Charles Schulz, MD.
AB  - One of the keys to the success of Annals of Clinical Psychiatry has always been
      the tireless efforts of our dedicated Editorial Board. We recently lost 2
      longtime Editorial Board members, Drs. Paul Michael Packman and S. Charles
      Schulz. Both will be greatly missed.

PMID- 29373614
TI  - The association of adverse mental health effects with repeated exposure to
      disasters.
AB  - BACKGROUND: It has been assumed that the mental health effects of repeated trauma
      should be incrementally greater than simple additive effects of separate trauma.
      However, repeated disasters afflicting the same population are uncommon. This
      study investigated psychiatric disorders following differential exposures to
      repeated disasters. METHODS: Mental health effects of exposure to repeated
      disasters of 547 individuals exposed to either flooding, tornadoes, dioxin
      contamination, and/or radioactive well water were assessed. Structured diagnostic
      interviews assessed prevalence of psychiatric disorders before and after each of
      the disasters. A multiple logistic regression model was used to test the
      association of post-disaster disorders after each flood with the total number of
      flood exposures, controlling for lifetime pre-disaster disorders. RESULTS:
      Approximately one-fifth to one-third of the disaster-exposed groups had a
      psychiatric disorder following exposure to disaster, but disaster-related
      posttraumatic stress disorder and incident psychiatric disorders were nonexistent
      or rare in both post-disaster periods. Most identified post-disaster
      psychopathology consisted of alcohol use that predated the disasters.
      CONCLUSIONS: Findings suggest that alcohol use disorder may be more
      representative of a risk factor for, rather than an outcome of, flood exposure.
      This possibility is supported by the high lifetime pre-flood prevalence of
      alcohol use disorders in flood plain populations.

PMID- 29373615
TI  - Is binge eating a cognitive disorder? Results from the International Mood
      Disorders Collaborative Project.
AB  - BACKGROUND: Individuals with binge eating disorder (BED) are differentially
      affected by attention-deficit/hyperactivity disorder (ADHD), obesity, and
      substance use disorder. We have investigated to what extent cognitive deficits
      are relevant to binge eating behavior (BEB). METHODS: Data from the International
      Mood Disorders Collaborative Project were retrospectively and cross-sectionally
      analyzed to compare individuals with and without BEB on measures of anhedonia and
      general cognitive functions (n = 566). BEB was assessed using items from the Mini
      International Neuropsychiatric Interview Plus 5.0.0 for DSM-IV-TR that correspond
      with DSM-5-defined diagnostic criteria for BED. Individuals currently prescribed
      benzodiazepines were excluded from analyses. RESULTS: Individuals with BEB were
      more likely to exhibit anhedonia (P = .044) and general cognitive (P = .005)
      symptoms, when compared to those without BEB. We also observed that individuals
      with BEB were more likely to have specific psychiatric (eg, ADHD) and medical
      (eg, obesity) disorders (P < .05). CONCLUSIONS: Our results suggest that a
      central disturbance in cognitive processes may be mechanistically relevant to the
      cause and treatment of BEB in adults.

PMID- 29373616
TI  - Differences in the cognitive profile of depression between racial groups.
AB  - BACKGROUND: There is little research concerning whether race is associated with
      different clinical presentations of psychiatric disorders. Understanding the
      racial aspects of cognitive differences among depressed adults could help
      identify specific targets for depression treatment. METHODS: We recruited 59
      participants (52.5% white, 47.5% African American), age 18 to 60, with a current
      diagnosis of major depressive disorder (MDD). All participants underwent a
      cognitive battery that included tasks assessing decision-making, response
      inhibition, working memory, and executive planning. Differences between white and
      African American groups were analyzed using analysis of variance or equivalent
      nonparametric tests. RESULTS: There were no differences in demographic variables
      of age, sex, and education, but white individuals reported a significantly
      earlier age of first depressive episode compared with African American
      individuals. The African American group, however, showed significantly lower
      quality of decision-making and less risk adjustment on the Cambridge Gambling
      Task, and made more errors on the Spatial Working Memory task. CONCLUSIONS: Our
      finding that specific cognitive domains differ as a function of racial
      differences in MDD might have differential prognostic and treatment implications.

PMID- 29373617
TI  - Determinants of cognitive function in individuals with type 2 diabetes mellitus:
      A meta-analysis.
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with deficits across
      multiple cognitive domains; however, the determinants of cognitive impairment in
      T2DM are not well characterized. We aimed to evaluate body mass index (BMI),
      glycemic control, and T2DM duration as moderators of cognitive dysfunction in
      T2DM. METHODS: We conducted a meta-analytic review of the literature reporting
      data on BMI, hemoglobin A1c (HbA1c), T2DM duration, and validated measures of
      processing speed (ie, Digit Symbol Substitution Test, Trail Making Test [TMT]-A),
      verbal learning and memory (ie, Rey Auditory Verbal Learning Test), and working
      memory/executive function (ie, TMT-B) among individuals with vs without T2DM.
      RESULTS: Individuals with T2DM demonstrated deficits across multiple cognitive
      domains (k = 40; n = 4,252 T2DM; n = 22,322 non-T2DM; effect sizes 0.21 to 0.35).
      Illness duration and BMI did not significantly moderate measures of cognition;
      however, higher HbA1c levels were significantly associated with deficits in
      measures of processing speed (R2 values 0.41 to 0.73, P < .01) and working
      memory/executive function (R2 = 0.62, P < .001). CONCLUSIONS: Adults with T2DM
      exhibited significant deficits across multiple domains of cognitive function.
      Additionally, we identified an association between poorer glycemic control and
      cognitive dysfunction. A clinical translation of our findings relates to the
      reduction in morbidity by improving glycemic control.

PMID- 29373618
TI  - Effectiveness of mindfulness-based stress reduction in a community sample over 2
      years.
AB  - BACKGROUND: Although numerous studies have demonstrated that mindfulness-based
      stress reduction (MBSR) improves clinical and nonclinical outcomes, few studies
      have followed MBSR participants for >12 months, and few have analyzed post
      intervention home practice. METHODS: We followed a community sample of 247 self
      referred adults for 2 years after completion of an 8-week MBSR program. Dependent
      variables, including self-reported anxiety, depression, perceived wellness,
      mindfulness, and duration and frequency of continued home practice, were measured
      before and after the program and every 6 months after. RESULTS: Participants
      reported significantly improved symptoms of depression and anxiety, increased
      perceived wellness, and increased mindfulness after the 8-week intervention
      compared with preintervention reports. These improvements persisted for 2 years.
      Correlations between post-intervention home practice and mindfulness indicated
      that individuals who continued to practice developed greater mindfulness, which
      was associated with improved mental health and wellness. CONCLUSIONS:
      Participants who completed the MBSR program reported significant improvements in
      anxiety, depression, perceived wellness, and mindfulness during the program.

PMID- 29373619
TI  - A brief history of polarity in mood and its diagnostic evolution.
AB  - BACKGROUND: We reviewed the historical development of diagnostic nomenclature and
      classification systems of mood disorders. METHODS: A literature search in PubMed
      and Google Scholar was performed using multiple search terms. Also, the criteria
      and classification of various mood disorders were reviewed and compared across
      all editions of DSM. We also reviewed several books and the references of the
      found articles. RESULTS: This review describes the historical development of the
      concepts and diagnostic nomenclature of mood disorders, including the
      encompassing of most of the now major depressive disorder under the prior manic
      depressive illness. Additionally, we examine how mood disorders have been
      developed, classified, and split into subcategories historically until the
      current classification. We observed that the modern nosology (DSM-5) leans a bit
      more toward a spectrum approach. CONCLUSIONS: The pendulum has swung a bit from
      splitting toward lumping. The current diagnostic system blurs some of the
      boundaries between bipolar and unipolar disorders, as in the case of changing
      nomenclature to "mixed features" in both types of illnesses. This is supported by
      many experts (and some studies) who advocate for the spectrum concept in mood at
      the phenotypic level. The spectrum concept is more supported by evidence and
      further examination driven by both unconfined clinical observations and
      biological anchor points and markers to scientifically examine the zones of
      rarity and boundaries between disorders. This would be more fruitful than the
      arbitrary DSM number of criteria or episode durations and the artificial
      separation of manic-depressive illness.

PMID- 29373620
TI  - Stuttering and levetiracetam: Case report and research proposal.

PMID- 29373621
TI  - Modafinil associated with new-onset obsessivecompulsive disorder.

PMID- 29373627
TI  - Comparison of Performance of the VIP and WMT in a Criminal Forensic Sample.
AB  - Objective: To compare the efficacy of the Validity Indicator Profile (VIP) and
      Word Memory Test (WMT) in a criminal forensic population. Method: Potential
      participants included 225 male evaluees from a maximum-security Federal prison
      referred for neuropsychological evaluation for either forensic purposes or for
      suspected neurocognitive dysfunction as part of a medical evaluation. Examinees
      were included in the analysis if administered the VIP (Verbal, Nonverbal, or both
      tests) and WMT along with at least two other freestanding PVTs; 74 satisfied
      these criteria. Participants were then categorized as having probable Malingered
      Neurocognitive Dysfunction (+MND) if they failed at least two freestanding
      validity indicators, negative for MND (-MND) if they passed all indicators, and
      Possible MND (pMND) if they failed one indicator. Results: Groups were very
      demographically similar. There were significant differences in WMT scores and
      distribution of VIP profiles across groups. Whether using traditional or
      investigative cut scores, and whether using the WMT with or without consideration
      of a GMIP profile, the WMT demonstrated superior sensitivity and specificity on
      nearly every comparison. Conclusions: The VIP, when interpreted in the
      traditional fashion, and the WMT with GMIP, both had more than adequate
      psychometric properties when used with criminal forensic evaluees, strengthening
      the body of literature supporting their use for these types of evaluations.
      Counting a positive on either of the VIP subtests as an indication of +MND
      improves the psychometric properties of the VIP slightly, although the WMT had
      the better overall classification accuracy.

PMID- 29373628
TI  - Effects of Personal Protective Equipment Use and Good Workplace Hygiene on
      Symptoms of Neurotoxicity in Solvent-Exposed Vehicle Spray Painters.
AB  - Objectives: To assess the association between the use of personal protective
      equipment (PPE) and good workplace hygiene and symptoms of neurotoxicity in
      solvent-exposed vehicle spray painters. Methods: Exposure control measures
      including PPE-use and workplace hygiene practices and symptoms of neurotoxicity
      were assessed in 267 vehicle repair spray painters. Symptoms were assessed using
      an adapted version of the EUROQUEST Questionnaire. Results: Frequent respirator
      and glove use was inversely and significantly associated with symptoms of
      neurotoxicity in a dose-dependent manner (P < 0.05 for trend) with the strongest
      protective effect found for consistent glove use (odds ratios [OR] 0.1-0.2, P <
      0.01, for reporting >=10 and >=5 symptoms). A clear dose-response trend was also
      observed when combining frequency of respirator and glove use (P < 0.05 for
      reporting >=5 and >=10 symptoms), with an overall reduction in risk of 90% (OR,
      0.1, P < 0.01) for those who consistently used both types of PPE. Protective
      effects were most pronounced for the symptom domains of psychosomatic (P < 0.05
      for trend, for combined PPE use), mood (P < 0.05), and memory and concentration
      symptoms combined (P < 0.05), with reductions in risk of >80%. Poor hygiene
      workplace practices, such as solvent exposure to multiple body parts (OR 3.4, P =
      0.11 for reporting >=10 symptoms), were associated with an increased risk of
      symptoms. When using a general workplace hygiene score derived from a combination
      of PPE-use and (good) workplace practice factors an inverse and significant dose
      response trend was observed for reporting >=5 (P < 0.01) and >=10 symptoms (P <
      0.01). Conclusions: This study has shown that PPE-use and good workplace hygiene
      are associated with a strongly reduced risk of symptoms of neurotoxicity in
      solvent-exposed vehicle spray painters.

PMID- 29373629
TI  - Are there tides within trees?
AB  - Background: Tree stem diameters and electrical stem potentials exhibit rhythmic
      variations with periodicities of 24-25 h. Under free-running conditions of
      constant light or darkness these rhythms were suggested to be mediated by the
      lunisolar gravitational force. Scope: To further unravel the regulation of tree
      stem diameter dilatations, many of the published time courses of diameter
      variations were re-evaluated in conjunction with the contemporaneous time courses
      of the lunisolar tidal acceleration. This was accomplished by application of the
      Etide program, which estimates, with high temporal resolution, local
      gravitational changes as a consequence of the diurnal variations of the lunisolar
      gravitational force due to the orbits and relative positions of Earth, Moon and
      Sun. In all instances investigated, it was evident that a synchronism exists
      between the times of the turning points of both the lunisolar tide and stem
      diameter variations when the direction of extension changes. This finding of
      synchrony documents that the lunisolar tide is a regulator of the tree stem
      diameter dilatations. Conclusions: Under the described experimental conditions,
      rhythms in tree stem diameter dilations and electrical stem potentials are
      controlled by the lunisolar gravitational acceleration.

PMID- 29373630
TI  - Reply: No evidence for rare TRAP1 mutations influencing the risk of idiopathic
      Parkinson's disease.

PMID- 29373631
TI  - Physiological and Anatomical Outputs of Rat Genital Cortex.
AB  - Rat somatosensory genital cortex contains a large sexually monomorphic
      representation of the penis in males and the clitoris in females. Genital cortex
      microstimulation-evoked movements of legs, trunk and genitals, which showed sex
      specific differences related to mating behaviors and included thrusting in males
      and lordosis-like movements in females. Erections/tumescence of penis or clitoris
      could not be evoked, however. Anterograde tracer injections into penis/clitoris
      cortex revealed eleven corticocortical and 10 subcortical projection targets,
      which were qualitatively similar in both sexes. Corticocortical genital-cortex
      projections innervated about 3% of the cortical surface and most were analog to
      other somatosensory projections targeting motor cortex, secondary somatosensory
      cortex, parietal cortex and perirhinal cortex. Corticocortical projections that
      differed from other parts of somatosensory cortex targeted male scrotum cortex,
      female vulva cortex, the somatosensory-ear-auditory-cortex-region and the caudal
      parietal area. Aligning cytoarchitectonic borders with motor topography, sensory
      genital responses and corticocortical projections identified a candidate region
      for genital motor cortex. Most subcortical genital-cortex-projections were analog
      to other thalamic, tectal or pontine projections of somatosensory cortex. Genital
      cortex-specific subcortical projections targeted amygdala and nucleus submedius
      and accumbens. Microstimulation-effects and projections support a sexual function
      of genital cortex and suggest that genital cortex is a major hub of sexual
      sensorimotor processing in rodents.

PMID- 29373633
TI  - On the Neural and Mechanistic Bases of Self-Control.
AB  - Intertemporal choice requires a dynamic interaction between valuation and
      deliberation processes. While evidence identifying candidate brain areas for each
      of these processes is well established, the precise mechanistic role carried out
      by each brain region is still debated. In this article, we present a
      computational model that clarifies the unique contribution of frontoparietal
      cortex regions to intertemporal decision making. The model we develop samples
      reward and delay information stochastically on a moment-by-moment basis. As
      preference for the choice alternatives evolves, dynamic inhibitory processes are
      executed by way of asymmetric lateral inhibition. We find that it is these
      lateral inhibition processes that best explain the contribution of frontoparietal
      regions to intertemporal decision making exhibited in our data.

PMID- 29373634
TI  - A Brief History of the Encoding of Hand Position by the Cerebral Cortex:
      Implications for Motor Control and Cognition.
AB  - Encoding hand position by the cerebral cortex is essential not only for the
      neural representation of the body image but also for different actions based on
      eye-hand coordination. These include reaching for visual objects as well as
      complex movement sequences, such as tea-making, tool use, and object
      construction, among many others. All these functions depend on a continuous
      refreshing of the hand position representation, relying on both predictive
      signaling and afferent information. The hand position influence on neural
      activity in the parietofrontal system, together with eye position signals, are
      the basic elements of an eye-hand matrix from which all the above functions can
      emerge and could be regarded as key features of a network with several entry
      points, command nodes and outflow pathways, as confirmed by the discovery of a
      direct parietospinal projection for the control of hand action. The integrity of
      this system is crucial for daily life, as testified by the consequences of
      cortical lesions, spanning from severe paralysis to complex forms of apraxia. In
      this review, I will sketch my personal understanding of the scientific and
      conceptual trajectory of a line of investigation with many unexpected influences
      on cortical function and disease, from motor behavior to cognition.

PMID- 29373635
TI  - Fear Extinction Recall Modulates Human Frontomedial Theta and Amygdala Activity.
AB  - Human functional magnetic resonance imaging (fMRI) and electroencephalography
      (EEG) studies, as well as animal studies, indicate that the amygdala and
      frontomedial brain regions are critically involved in conditioned fear and that
      frontomedial oscillations in the theta range (4-8 Hz) may support communication
      between these brain regions. However, few studies have used a multimodal approach
      to probe interactions among these key regions in humans. Here, our goal was to
      bridge the gap between prior human fMRI, EEG, and animal findings. Using
      simultaneous EEG-fMRI recordings 24 h after fear conditioning and extinction,
      conditioned stimuli presented (CS+E, CS-E) and not presented during extinction
      (CS+N, CS-N) were compared to identify effects specific to extinction versus fear
      recall. Differential (CS+ vs. CS-) electrodermal, frontomedial theta (EEG) and
      amygdala responses (fMRI) were reduced for extinguished versus nonextinguished
      stimuli. Importantly, effects on theta power covaried with effects on amygdala
      activation. Fear and extinction recall as indicated by theta explained 60% of the
      variance for the analogous effect in the right amygdala. Our findings show for
      the first time the interplay of amygdala and frontomedial theta activity during
      fear and extinction recall in humans and provide insight into neural circuits
      consistently linked with top-down amygdala modulation in rodents.

PMID- 29373636
TI  - Visual Attention and Math Performance in Survivors of Childhood Acute
      Lymphoblastic Leukemia.
AB  - Objective: Attentional and academic difficulties, particularly in math, are
      common in survivors of childhood acute lymphoblastic leukemia (ALL). Of cognitive
      deficits experienced by survivors of childhood ALL, attention deficits may be
      particularly responsive to intervention. However, it is unknown whether deficits
      in particular aspects of attention are associated with deficits in math skills.
      The current study investigated relationships between math calculation skills,
      performance on an objective measure of sustained attention, and parent- and
      teacher-reported attention difficulties. Method: Twenty-four survivors of
      childhood ALL (Mage = 13.5 years, SD = 2.8 years) completed a computerized
      measure of sustained attention and response control and a written measure of math
      calculation skills in the context of a comprehensive clinical neuropsychological
      evaluation. Parent and teacher ratings of inattention and impulsivity were
      obtained. Results: Visual response control and visual attention accounted for
      26.4% of the variance observed among math performance scores after controlling
      for IQ (p < .05). Teacher-rated, but not parent-rated, inattention was
      significantly negatively correlated with math calculation scores. Conclusions:
      Consistency of responses to visual stimuli on a computerized measure of attention
      is a unique predictor of variance in math performance among survivors of
      childhood ALL. Objective testing of visual response control, rather than parent
      rated attentional problems, may have clinical utility in identifying ALL
      survivors at risk for math difficulties.

PMID- 29373637
TI  - No evidence for rare TRAP1 mutations influencing the risk of idiopathic
      Parkinson's disease.

PMID- 29373632
TI  - Neurotransmitter deficits from frontotemporal lobar degeneration.
AB  - Frontotemporal lobar degeneration causes a spectrum of complex degenerative
      disorders including frontotemporal dementia, progressive supranuclear palsy and
      corticobasal syndrome, each of which is associated with changes in the principal
      neurotransmitter systems. We review the evidence for these neurochemical changes
      and propose that they contribute to symptomatology of frontotemporal lobar
      degeneration, over and above neuronal loss and atrophy. Despite the development
      of disease-modifying therapies, aiming to slow neuropathological progression, it
      remains important to advance symptomatic treatments to reduce the disease burden
      and improve patients' and carers' quality of life. We propose that targeting the
      selective deficiencies in neurotransmitter systems, including dopamine,
      noradrenaline, serotonin, acetylcholine, glutamate and gamma-aminobutyric acid is
      an important strategy towards this goal. We summarize the current evidence-base
      for pharmacological treatments and suggest strategies to improve the development
      of new, effective pharmacological treatments.

PMID- 29373638
TI  - Renal Considerations in the Treatment of Hypertension.
AB  - There are renal implications when employing intensive blood pressure control
      strategies. While this approach provides cardiovascular benefit in patients with
      and without chronic kidney disease, the impact on renal disease progression
      differs according to the pattern of underlying renal injury. In the setting of
      proteinuria, stringent blood pressure control has generally conferred a
      protective effect on renal disease progression, but in the absence of
      proteinuria, this benefit tends to be much less impressive. Thiazide diuretics
      are frequently part of the regimen to achieve intensive blood pressure control.
      These drugs can cause hyponatremia and present with biochemical evidence
      mimicking the syndrome of inappropriate antidiuretic hormone secretion. Altered
      prostaglandin transport may explain the unique susceptibility to this
      complication observed in some patients. Hyperkalemia is also a complication of
      intensive blood pressure lowering particularly in the setting of renin
      angiotensin-aldosterone blockade. There are strategies and new drugs now
      available that can allow use of these blockers and at the same time ensure a
      normal plasma potassium concentration.

PMID- 29373640
TI  - Quantifying within-plant spatial heterogeneity in carbohydrate availability in
      cotton using a local-pool model.
AB  - Background and Aims: Within-plant spatial heterogeneity in the production of and
      demand for assimilates may have major implications for the formation of fruits.
      Spatial heterogeneity is related to organ age, but also to position on the plant.
      This study quantifies the variation in local carbohydrate availability for the
      phytomers in the same cohort using a cotton growth model that captures
      carbohydrate production in phytomers and carbohydrate movement between phytomers.
      Methods: Based on field observations, we developed a functional-structural plant
      model of cotton that simulates production and storage of carbohydrates in
      individual phytomers and transport of surplus to other phytomers. Simulated total
      leaf area, total above-ground dry mass, dry mass distribution along the stem, and
      dry mass allocation fractions to each organ at the plant level were compared with
      field observations for plants grown at different densities. The distribution of
      local carbohydrate availability throughout the plant was characterized and a
      sensitivity analysis was conducted regarding the value of the carbohydrate
      transport coefficient. Key Results: The model reproduced cotton leaf expansion
      and dry mass allocation across plant densities adequately. Individual leaf area
      was underestimated at very high plant densities. Best correspondence with
      measured plant traits was obtained for a value of the transport coefficient of
      0.1 d-1. The simulated translocation of carbohydrates agreed well with results
      from C-labelling studies. Moreover, simulation results revealed the heterogeneous
      pattern of local carbohydrate availability over the plant as an emergent model
      property. Conclusions: This modelling study shows how heterogeneity in local
      carbohydrate production within the plant structure in combination with
      limitations in transport result in heterogeneous satisfaction of demand over the
      plant. This model provides a tool to explore phenomena in cotton that are thought
      to be determined by local carbohydrate availability, such as branching pattern
      and fruit abortion in relation to climate and crop management.

PMID- 29373641
TI  - Cortical Responses to Input From Distant Areas are Modulated by Local Spontaneous
      Alpha/Beta Oscillations.
AB  - Any given area in human cortex may receive input from multiple, functionally
      heterogeneous areas, potentially representing different processing threads. Alpha
      (8-13 Hz) and beta oscillations (13-20 Hz) have been hypothesized by other
      investigators to gate local cortical processing, but their influence on cortical
      responses to input from other cortical areas is unknown. To study this, we
      measured the effect of local oscillatory power and phase on cortical responses
      elicited by single-pulse electrical stimulation (SPES) at distant cortical sites,
      in awake human subjects implanted with intracranial electrodes for epilepsy
      surgery. In 4 out of 5 subjects, the amplitudes of corticocortical evoked
      potentials (CCEPs) elicited by distant SPES were reproducibly modulated by the
      power, but not the phase, of local oscillations in alpha and beta frequencies.
      Specifically, CCEP amplitudes were higher when average oscillatory power just
      before distant SPES (-110 to -10 ms) was high. This effect was observed in only a
      subset (0-33%) of sites with CCEPs and, like the CCEPs themselves, varied with
      stimulation at different distant sites. Our results suggest that although alpha
      and beta oscillations may gate local processing, they may also enhance the
      responsiveness of cortex to input from distant cortical sites.

PMID- 29373639
TI  - A novel metabolism-based phenotypic drug discovery platform in zebrafish uncovers
      HDACs 1 and 3 as a potential combined anti-seizure drug target.
AB  - Despite the development of newer anti-seizure medications over the past 50 years,
      30-40% of patients with epilepsy remain refractory to treatment. One explanation
      for this lack of progress is that the current screening process is largely biased
      towards transmembrane channels and receptors, and ignores intracellular proteins
      and enzymes that might serve as efficacious molecular targets. Here, we report
      the development of a novel drug screening platform that harnesses the power of
      zebrafish genetics and combines it with in vivo bioenergetics screening assays to
      uncover therapeutic agents that improve mitochondrial health in diseased animals.
      By screening commercially available chemical libraries of approved drugs, for
      which the molecular targets and pathways are well characterized, we were able to
      reverse-identify the proteins targeted by efficacious compounds and confirm the
      physiological roles that they play by utilizing other pharmacological ligands.
      Indeed, using an 870-compound screen in kcna1-morpholino epileptic zebrafish
      larvae, we uncovered vorinostat (ZolinzaTM; suberanilohydroxamic acid, SAHA) as a
      potent anti-seizure agent. We further demonstrated that vorinostat decreased
      average daily seizures by ~60% in epileptic Kcna1-null mice using video-EEG
      recordings. Given that vorinostat is a broad histone deacetylase (HDAC)
      inhibitor, we then delineated a specific subset of HDACs, namely HDACs 1 and 3,
      as potential drug targets for future screening. In summary, we have developed a
      novel phenotypic, metabolism-based experimental therapeutics platform that can be
      used to identify new molecular targets for future drug discovery in epilepsy.

PMID- 29373643
TI  - Corrigendum.

PMID- 29373642
TI  - Feeling stretched or compressed? The multiple mechanosensitive responses of wood
      formation to bending.
AB  - Background and Aims: Trees constantly experience wind, perceive resulting
      mechanical cues, and modify their growth and development accordingly. Previous
      studies have demonstrated that multiple bending treatments trigger ovalization of
      the stem and the formation of flexure wood in gymnosperms, but ovalization and
      flexure wood have rarely been studied in angiosperms, and none of the experiments
      conducted so far has used multidirectional bending treatments at controlled
      intensities. Assuming that bending involves tensile and compressive strain, we
      hypothesized that different local strains may generate specific growth and wood
      differentiation responses. Methods: Basal parts of young poplar stems were
      subjected to multiple transient controlled unidirectional bending treatments
      during 8 weeks, which enabled a distinction to be made between the wood formed
      under tensile or compressive flexural strains. This set-up enabled a local
      analysis of poplar stem responses to multiple stem bending treatments at growth,
      anatomical, biochemical and molecular levels. Key Results: In response to
      multiple unidirectional bending treatments, poplar stems developed significant
      cross-sectional ovalization. At the tissue level, some aspects of wood
      differentiation were similarly modulated in the compressed and stretched zones
      (vessel frequency and diameter of fibres without a G-layer), whereas other
      anatomical traits (vessel diameter, G-layer formation, diameter of fibres with a
      G-layer and microfibril angle) and the expression of fasciclin-encoding genes
      were differentially modulated in the two zones. Conclusions: This work leads us
      to propose new terminologies to distinguish the 'flexure wood' produced in
      response to multiple bidirectional bending treatments from wood produced under
      transient tensile strain (tensile flexure wood; TFW) or under transient
      compressive strain (compressive flexure wood; CFW). By highlighting similarities
      and differences between tension wood and TFW and by demonstrating that plants
      could have the ability to discriminate positive strains from negative strains,
      this work provides new insight into the mechanisms of mechanosensitivity in
      plants.

PMID- 29373644
TI  - Control of plant leaf movements by the lunisolar tidal force.
AB  - Background: Investigations into the diurnal ascent and descent of leaves of beans
      and other species, as well as experimental interventions into these movements,
      such as exposures to light at different times during the movement cycle, led to
      the concept of an endogenous 'clock' as a regulator of these oscillations. The
      causal origin of leaf movement can be traced to processes that modulate cell
      volume in target tissues of the pulvinus and petiole. However, these elements of
      the leaf-movement process do not sufficiently account for the rhythms that are
      generated following germination in constant light or dark conditions, or when
      plants are transferred to similar free-running conditions. Scope: To further
      unravel the regulation of leaf-movement rhythms, many of the published time
      courses of leaf movements that provided evidence for the concept of the
      endogenous clock were analysed in conjunction with the contemporaneous time
      courses of the lunisolar tidal acceleration. This was accomplished by application
      of the Etide program, which estimates, with high temporal resolution, local
      gravitational changes as a consequence of the diurnal variations of the lunisolar
      gravitational force due to the orbits and relative positions of Earth, Moon and
      Sun. To substantiate the results obtained in earthbound laboratories additional
      experiments were performed in the International Space Station (ISS). Tidal
      recurrence within the ISS exhibited a periodicity of 45 min. In all instances
      investigated, it was evident that a synchronism exists between the times of the
      turning points of both the lunisolar tide and of the leaftide when the direction
      of leaf movement changes. This finding of synchrony documents that the lunisolar
      tide is a regulator of the leaftide, and that the rhythm of leaf movement is not
      of endogenous origin but is an expression of an exogenous lunisolar clock
      impressed upon the leaf-movement apparatus. Conclusions: A huge number of
      correlations between leaftide and Etide time courses were established for leaf
      movement rhythms in natural conditions of the greenhouse, in conditions of
      constant light or dark, and under the microgravity conditions of the
      International Space Station. Even the apparently spontaneous short-period, small
      amplitude rhythms recorded from leaves under unusual growth conditions are
      consistent with the hypothesis of a lunisolar zeitgeber. Synchronism between
      leaftide and Etide is discussed in terms of classical and quantum mechanics.

PMID- 29373645
TI  - Influence of external stenting on venous graft flow parameters in coronary artery
      bypass grafting: a randomized study.
AB  - OBJECTIVES: Long-term patency of saphenous vein grafts (SVGs) remains a concern
      after coronary artery bypass grafting. Interventions to overcome this problem
      include monitoring intraoperative flow profile and, more recently, external
      stenting of SVGs. It is not known to what extent external stenting changes the
      perioperative flow characteristics of SVGs. The aim of this study was to assess
      whether the presence of an external stent affects perioperative graft flow
      parameters as evaluated by transit time flowmetry. METHODS: Thirty-five patients
      were included from 1 centre participating in a multicentre, randomized clinical
      trial of external stenting of SVGs. Patients were eligible if scheduled for on
      pump multivessel coronary artery bypass grafting including planned SVGs to both
      the right and the left coronary territories. Each patient received external
      stenting of a single SVG randomly allocated intraoperatively to either coronary
      territory. The primary end-points were mean graft flow, pulsatility index,
      percentage of diastolic filling and percentage of backward flow in stented versus
      non-stented SVGs. RESULTS: External stenting was performed in 17 SVGs supplying
      the left territory (20 non-stented SVGs for control) and in 18 SVGs supplying the
      right territory (18 non-stented SVGs for control). No significant difference was
      found in flow parameters between stented and non-stented SVGs in the overall
      group or between pre-defined groups of SVGs supplying the right and left
      territories, respectively. CONCLUSIONS: External stenting of SVGs do not affect
      intraoperative flow parameters significantly. CLINICAL TRIAL REGISTRATION:
      clinicaltrials.gov identifier: NCT02511834.

PMID- 29373646
TI  - Somatic symptoms and internalizing problems in urban youth: a cross-cultural
      comparison of Czech and Russian adolescents.
AB  - Background: Although the association between somatic complaints and internalizing
      problems (anxiety, somatic anxiety and depression) is well established, it
      remains unclear whether the pattern of this relationship differs by gender and in
      different cultures. The aim of this study was to examine cross-cultural and
      gender-specific differences in the association between somatic complaints and
      internalizing problems in youth from the Czech Republic and Russia. Methods: The
      Social and Health Assessment, a self-report survey, was completed by
      representative community samples of adolescents, age 12-17 years, from the Czech
      Republic (N = 4770) and Russia (N = 2728). Results: A strong association was
      observed between somatic complaints and internalizing psychopathology. Although
      the levels of internalizing problems differed by country and gender, they
      increased together with and largely in a similar way to somatic complaints for
      boys and girls in both countries. Conclusion: The association between somatic
      symptoms and internalizing problems seems to be similar for boys and girls across
      cultures.

PMID- 29373647
TI  - Eggerthella lenta Bloodstream Infections Are Associated With Increased Mortality
      Following Empiric Piperacillin-Tazobactam (TZP) Monotherapy: A Population-based
      Cohort Study.
AB  - Background: Eggerthella lenta is a anaerobic gram-positive bacilli associated
      with polymicrobial intraabdominal infections. Recently, E. lenta was recognized
      as an important cause of anaerobic bloodstream infections (BSIs) associated with
      high mortality. Eggerthella lenta has been reported to have high minimal
      inhibitory concentrations (MICs) to piperacillin-tazobactam (TZP), a broad
      spectrum antibiotic with anaerobic coverage commonly used in multiple centers for
      empiric treatment of abdominal sepsis. Methods: We describe a retrospective
      population-based analysis of invasive E. lenta infections from 2009 through 2015.
      A logistic regression analysis for 30-day mortality risk factors was conducted.
      Results: We identified 107 E. lenta infections, 95 (89%) were BSIs, 11 (10%) skin
      and soft tissue infections, and 1 intraabdominal abscess. Polymicrobial
      infections were found in 40%; 72% of isolates were from a gastrointestinal
      source, most commonly appendicitis (33%) of which two-thirds were perforated. TZP
      MIC50 and MIC90 for E. lenta isolates were 32 MUg/mL and 64 MUg/mL, respectively.
      The overall 30-day mortality for BSI was 23% and was independently associated
      with empiric TZP monotherapy (odds ratio [OR], 4.4; 95% confidence interval [CI],
      1.2-16; P = .02) and intensive care unit stay (OR, 6.2; 95% CI, 1.4-27.3; P =
      .01). Thirty-day mortality rates were significantly influenced by the use of
      different TZP MIC breakpoints. Conclusions: Our results demonstrate the increased
      recognition of E. lenta as an anaerobic opportunistic pathogen and highlight the
      need for improved empiric antimicrobial guidelines and TZP MIC breakpoints with
      better correlation to clinical outcomes to guide appropriate management of
      invasive E. lenta infections.

PMID- 29373648
TI  - Management and Outcomes of Childhood Renal Artery Stenosis and Middle Aortic
      Syndrome.
AB  - BACKGROUND: Renal artery stenosis (RAS) in isolation or in conjunction with
      middle aortic syndrome (MAS) are important vascular causes of childhood
      hypertension. Few longitudinal studies have assessed the risk of surgical or
      endovascular intervention, and outcomes by etiology or extent of vascular
      disease. METHODS: In a retrospective study of 93 children seen over 30 years with
      RAS and/or MAS, data on vascular involvement (isolated RAS vs. RAS with MAS),
      etiology (unknown, inflammatory, or genetic), and management were collected. Time
      to first intervention (endovascular or surgical) was assessed by Cox regression.
      Mixed-effects analysis examined the longitudinal change in blood pressure after
      intervention compared to antihypertensive medications alone. RESULTS: Children
      were 7.0 +/- 5.4 years old. Etiology was unknown in 50%, genetic in 26% and
      inflammatory in 24% of children. Children had isolated RAS (49%) or MAS with or
      without RAS (51%). Overall, 70% were managed with surgical or endovascular
      intervention. After adjusting for age, sex, and systolic blood pressure, children
      with unknown etiology had a higher risk of intervention compared to those with
      genetic and inflammatory diseases (hazard ratio 3.1, 95% confidence interval [CI]
      1.7, 5.6). Children with RAS and MAS were less likely to receive intervention
      (hazard ratio 0.4, 95% CI 0.2, 0.8) than isolated RAS. Over a median follow-up of
      2 years, 65% remained hypertensive. The longitudinal changes in systolic blood
      pressure did not differ by etiology, or between interventional and medical
      management. CONCLUSIONS: Hypertension persists despite endovascular or surgical
      management of childhood RAS and MAS highlighting the importance of close
      monitoring and ongoing medical management.

PMID- 29373649
TI  - Application of hybrid Stage I palliation for patients with two ventricular
      cavities and hypoplastic left heart structures.
AB  - OBJECTIVES: To assess the feasibility of hybrid Stage I palliation consisting of
      bilateral pulmonary artery bandings and ductal stenting for patients with 2
      ventricular cavities and hypoplastic left heart structures. METHODS: Eleven
      consecutive patients who underwent hybrid Stage I palliation between 2010 and
      2017 were enrolled. The diagnoses were interrupted aortic arch/coarctation of the
      aorta, ventricular septal defect and significant left ventricular (LV) outflow
      tract obstruction in 5 patients, critical aortic stenosis and reduced LV
      contraction in 3 patients and hypoplastic left heart complex in 3 patients.
      RESULTS: The median age at definitive surgery was 12 months (range 6-22 months).
      During the mean follow-up period of 24 months (range 9-83 months) following the
      definitive surgery, there was 1 death. Two patients with interrupted aortic
      arch/coarctation of the aorta did not undergo the Yasui operation but underwent
      arch repair and ventricular septal defect closure after the growth of the aortic
      valve and LV outflow tract. For 2 of the 3 patients with critical aortic
      stenosis, biventricular repair was performed. Of the 3 patients with hypoplastic
      left heart complex, 2 patients showed growth of the mitral valve and left
      ventricle following LV rehabilitation by balloon pulmonary artery dilatation or
      surgical debanding of the banded pulmonary arteries and subsequently underwent
      biventricular repair, which resulted in 1 death. CONCLUSIONS: Hybrid Stage I
      palliation would be a safe and beneficial treatment for patients with 2
      ventricles, as a bridge to decide whether and how to achieve a biventricular
      repair and whether it should be preceded by a preliminary LV rehabilitation.

PMID- 29373650
TI  - Melatonin protects oocytes from MEHP exposure-induced meiosis defects in porcine.
AB  - In 2011, DEHP (plasticizer) was reported to illegally be added in food and
      beverage products in Taiwan, which caused great concerns about food safety
      worldwide. DHEP has multiple toxic effects to human and animals such as endocrine
      disruption, cardiotoxicity, reproductive function, and development defects.
      However, the toxic effects of DEHP on mammalian oocyte quality are still unclear.
      Since MEHP is the active metabolite of DEHP in vivo, in this study we used
      porcine oocyte as model to explore the effects of MEHP on oocyte maturation and
      we also studied the effects of melatonin administration on MEHP exposure-induced
      meiosis defects. Our results showed that exposure to MEHP significantly decreased
      the polar body extrusion rate in porcine oocytes. Further study showed that cell
      cycle progression, meiotic spindle organization, and actin assembly were all
      disturbed after MEHP exposure. Moreover, the DNA and histone methylation levels
      were also affected, showing with altered 5mC and H3K4me2 levels. These results
      indicated that MEHP affected porcine oocyte maturation, while MEHP exposure
      induced meiotic defects were all remarkably ameliorated by the administration of
      melatonin in porcine oocytes. We further tried to explore the causes of MEHP
      toxicity on oocytes, and we found that MEHP exposure resulted in significant
      elevations of oxidative stress and induced early apoptosis as well as elevated
      autophagy, while melatonin administration could reduce these. Taken together, our
      results indicated that MEHP exposure induced deterioration of oocyte quality,
      whereas melatonin supplement showed amelioration on oocyte maturation through its
      rescue effects on oocyte oxidative stress-mediated apoptosis and autophagy.

PMID- 29373651
TI  - Extracellular matrix glycation and receptor for advanced glycation end-products
      activation: a missing piece in the puzzle of the association between diabetes and
      cancer.
AB  - A growing body of epidemiologic evidence suggests that people with diabetes are
      at a significantly higher risk of many forms of cancer. However, the molecular
      mechanisms underlying this association are not fully understood. Cancer cells are
      surrounded by a complex milieu, also known as tumor microenvironment, which
      contributes to the development and metastasis of tumors. Of note, one of the
      major components of this niche is the extracellular matrix (ECM), which becomes
      highly disorganized during neoplastic progression, thereby stimulating cancer
      cell transformation, growth and spread. One of the consequences of chronic
      hyperglycemia, the most frequently observed sign of diabetes and the etiological
      source of diabetes complications, is the irreversible glycation and oxidation of
      proteins and lipids leading to the formation of the advanced glycation end
      products (AGEs). These compounds may covalently crosslink and biochemically
      modify structure and functions of many proteins, and AGEs accumulation is
      particularly high in long-living proteins with low biological turnover, features
      that are shared by most, if not all, ECM proteins. AGEs-modified proteins are
      recognized by AGE-binding proteins, and thus glycated ECM components have the
      potential to trigger Receptor for advanced glycation end-products-dependent
      mechanisms. The biological consequence of receptor for advanced glycation end
      products activation mechanisms seems to be connected, in different ways, to drive
      some hallmarks of cancer onset and tumor growth. The present review intends to
      highlight the potential impact of ECM glycation on tumor progression by
      triggering receptor for advanced glycation end-products-mediated mechanisms.

PMID- 29373652
TI  - Impact of adenotonsillectomy on the dentofacial development of obstructed
      children.

PMID- 29373653
TI  - Presynaptic GABAA Receptors Modulate Thalamocortical Inputs in Layer 4 of Rat V1.
AB  - Fast inhibitory GABAergic transmission plays a fundamental role in neural
      circuits. Current theories of cortical function assume that fast GABAergic
      inhibition acts via GABAA receptors on postsynaptic neurons, while presynaptic
      effects of GABA depend on GABAB receptor activation. Manipulations of GABAA
      receptor activity in vivo produced different effects on cortical function, which
      were generally ascribed to the mode of action of a drug, more than its site of
      action. Here we show that in rodent primary visual cortex, alpha4-containing
      GABAA receptors can be located on subsets of glutamatergic and GABAergic
      presynaptic terminals and decrease synaptic transmission. Our data provide a
      novel mechanistic insight into the effects of changes in cortical inhibition; the
      ability to modulate inputs onto cortical circuits locally, via presynaptic
      regulation of release by GABAA receptors.

PMID- 29373654
TI  - Behavioral Responses of Pityophthorus juglandis (Coleoptera: Curculionidae:
      Scolytinae) to Volatiles of Black Walnut and Geosmithia morbida (Ascomycota:
      Hypocreales: Bionectriaceae), the Causal Agent of Thousand Cankers Disease.
AB  - Thousand cankers disease (TCD) is a pest complex formed by the association of the
      walnut twig beetle (WTB), Pityophthorus juglandis Blackman (Coleoptera:
      Curculionidae: Scolytinae), with the fungal pathogen Geosmithia morbida Kolarik,
      Freeland, Utley and Tisserat (Ascomycota: Hypocreales: Bionectriaceae). Current
      monitoring and detection efforts for WTB rely on a pheromone lure that is
      effective over a limited distance while plant- and fungal-derived volatiles that
      may facilitate host location remain poorly understood. In this study, we test the
      hypothesis that adult beetles are attracted to volatiles of black walnut, Juglans
      nigra L. (Juglandaceae), and the pathogen, G. morbida. We measured the response
      of beetles to head-space volatiles collected from leaves and stems of 12
      genotypes of black walnut and found genotypic variation in the attractiveness of
      host trees to adult WTB. Volatile profiles of the most attractive genotypes
      contained more alpha-pinene and beta-pinene, and adult beetles were attracted to
      both of these compounds in olfactometer bioassays. In bioassays, we also
      demonstrated that adult WTB are attracted to volatiles of G. morbida. These
      findings suggest that, in addition to the aggregation pheromone, dispersing WTB
      potentially use host plant and fungal volatiles to locate suitable larval hosts.
      Finally, we conducted a field experiment to determine the extent to which
      ethanol, a common attractant for bark beetles, and limonene, a known bark beetle
      repellent, influence the behavior of adult WTB to pheromone-baited traps.
      Although ethanol did not increase trap capture, WTB were repelled by limonene,
      suggesting that this compound could be used to manipulate and manage WTB
      populations.

PMID- 29373655
TI  - Development and Validation of an Analytical Methodology Based on Liquid
      Chromatography-Electrospray Tandem Mass Spectrometry for the Simultaneous
      Determination of Phenolic Compounds in Olive Leaf Extract.
AB  - A simple method was validated for the analysis of 31 phenolic compounds using
      liquid chromatography-electrospray tandem mass spectrometry. Proposed method was
      successfully applied to the determination of phenolic compounds in an olive leaf
      extract and 24 compounds were analyzed quantitatively. Olive biophenols were
      extracted from olive leaves by using microwave-assisted extraction with
      acceptable recovery values between 78.1 and 108.7%. Good linearities were
      obtained with correlation coefficients over 0.9916 from calibration curves of the
      phenolic compounds. The limits of quantifications were from 0.14 to 3.2 MUg g-1.
      Intra-day and inter-day precision studies indicated that the proposed method was
      repeatable. As a result, it was confirmed that the proposed method was highly
      reliable for determination of the phenolic species in olive leaf extracts.

PMID- 29373657
TI  - Cardiac desmoid tumour.

PMID- 29373658
TI  - The outcome of reoperative pulmonary endarterectomy surgery.
AB  - OBJECTIVES: Pulmonary endarterectomy (PEA) is the treatment of choice for
      patients with chronic thromboembolic pulmonary hypertension (PH). Despite
      excellent outcomes following PEA, a small proportion of patients have residual
      proximal disease or present with recurrent chronic thromboembolic PH and may
      benefit from further surgery. The aim of this study was to analyse outcomes
      following reoperative PEA at a high-volume national tertiary referral centre for
      the management of chronic thromboembolic PH. METHODS: This retrospective analysis
      was performed using our prospectively maintained PH database to identify all
      patients who underwent reoperative PEA surgery between the commencement of the
      programme in 1997 and January 2017, and the patients' data were collected for
      analysis. RESULTS: Twelve patients underwent reoperative PEA during the period of
      study. The mean interval between primary procedure and reoperative procedure was
      6.3 years. Significant improvements were observed in pulmonary haemodynamics
      following reoperative PEA. Mean pulmonary arterial pressure decreased from 46.8
      to 29.8 mmHg (P < 0.0001) and pulmonary vascular resistance decreased from 662 to
      362 dyne.s.cm-5 (P = 0.0007). A significant functional improvement in the 6-min
      walking test distance was also observed, increasing from 327 to 460 m at 6 months
      postoperatively (P = 0.0018). Median length of hospital stay was 12 days. In
      hospital mortality was 8.3% with 1-year survival of 83.3%. CONCLUSIONS:
      Reoperative PEA is technically possible and relatively safe, achieving good
      functional and physiological outcomes. Patients must be carefully selected by a
      multidisciplinary team, and surgery should be performed in experienced centres.

PMID- 29373659
TI  - Simultaneous Aesthetic Eyelid Surgery and Orbital Decompression for
      Rehabilitation of Thyroid Eye Disease: The One-Stage Approach.
AB  - Background: Aesthetic rehabilitation of thyroid orbitopathy includes orbital
      decompression, correction of eyelid retraction, and aesthetic blepharoplasty,
      performed traditionally in separate stages. Objectives: To report the results of
      orbital decompression surgery associated with aesthetic eyelid surgery in one
      stage for aesthetic rehabilitation of patients affected by thyroid eye disease.
      Methods: Retrospective, multicentric study including 40 consecutive patients, who
      underwent orbital decompression surgery associated with aesthetic eyelid surgery
      in two centers: Genova (group 1) + Buenos Aires (group 2). Surgical techniques
      are described in detail. Results: Mean patient age in the study group was 41.2,
      85% of the patients were female, and minimum follow-up time was 12 months, with
      average follow up of 27 months. All patients underwent orbital decompression; at
      the same time, 26 patients (65%) underwent bilateral upper blepharoplasty and 32
      patients (80%) underwent transconjunctival lower blepharoplasty. Associated upper
      eyelid procedures included 23 patients (58%) undergoing upper eyelid retraction
      repair, 9 patients (23%) undergoing associated inferior retractor recession, and
      12 patients (30%) closed transcanthal lateral canthopexy. Seven patients (17%)
      needed strabismus surgery for the treatment of new-onset diplopia and none
      required further revision eyelid surgery. Conclusions: Shorr and Seiff suggested
      4 stages of surgical rehabilitation: (1) orbital decompression; (2) eye muscle
      surgery; (3) correction of eyelid retraction; and (4) removal of excess fat and
      skin. This is the first study to suggest single-stage aesthetic rehabilitation
      consisting of combined orbital decompression and aesthetic eyelid surgery. This
      approach has high patient satisfaction and significant reduction in direct and
      indirect healthcare costs. Level of Evidence 4: 

PMID- 29373656
TI  - Role of smooth muscle cells in coronary artery bypass grafting failure.
AB  - Atherosclerosis is the underlying pathology of many cardiovascular diseases. The
      formation and rupture of atherosclerotic plaques in the coronary arteries results
      in angina and myocardial infarction. Venous coronary artery bypass grafts are
      designed to reduce the consequences of atherosclerosis in the coronary arteries
      by diverting blood flow around the atherosclerotic plaques. However, vein grafts
      suffer a high failure rate due to intimal thickening that occurs as a result of
      vascular cell injury and activation and can act as 'a soil' for subsequent
      atherosclerotic plaque formation. A clinically-proven method for the reduction of
      vein graft intimal thickening and subsequent major adverse clinical events is
      currently not available. Consequently, a greater understanding of the underlying
      mechanisms of intimal thickening may be beneficial for the design of future
      therapies for vein graft failure. Vein grafting induces inflammation and
      endothelial cell damage and dysfunction, that promotes vascular smooth muscle
      cell (VSMC) migration, and proliferation. Injury to the wall of the vein as a
      result of grafting leads to the production of chemoattractants, remodelling of
      the extracellular matrix and cell-cell contacts; which all contribute to the
      induction of VSMC migration and proliferation. This review focuses on the role of
      altered behaviour of VSMCs in the vein graft and some of the factors which
      critically lead to intimal thickening that pre-disposes the vein graft to further
      atherosclerosis and re-occurrence of symptoms in the patient.

PMID- 29373660
TI  - Elucidating the interaction between light competition and herbivore feeding
      patterns using functional-structural plant modelling.
AB  - Background and Aims: Plants usually compete with neighbouring plants for
      resources such as light as well as defend themselves against herbivorous insects.
      This requires investment of limiting resources, resulting in optimal resource
      distribution patterns and trade-offs between growth- and defence-related traits.
      A plant's competitive success is determined by the spatial distribution of its
      resources in the canopy. The spatial distribution of herbivory in the canopy in
      turn differs between herbivore species as the level of herbivore specialization
      determines their response to the distribution of resources and defences in the
      canopy. Here, we investigated to what extent competition for light affects plant
      susceptibility to herbivores with different feeding preferences. Methods: To
      quantify interactions between herbivory and competition, we developed and
      evaluated a 3-D spatially explicit functional-structural plant model for Brassica
      nigra that mechanistically simulates competition in a dynamic light environment,
      and also explicitly models leaf area removal by herbivores with different feeding
      preferences. With this novel approach, we can quantitatively explore the extent
      to which herbivore feeding location and light competition interact in their
      effect on plant performance. Key Results: Our results indicate that there is
      indeed a strong interaction between levels of plant-plant competition and
      herbivore feeding preference. When plants did not compete, herbivory had
      relatively small effects irrespective of feeding preference. Conversely, when
      plants competed, herbivores with a preference for young leaves had a strong
      negative effect on the competitiveness and subsequent performance of the plant,
      whereas herbivores with a preference for old leaves did not. Conclusions: Our
      study predicts how plant susceptibility to herbivory depends on the composition
      of the herbivore community and the level of plant competition, and highlights the
      importance of considering the full range of dynamics in plant-plant-herbivore
      interactions.

PMID- 29373662
TI  - Massive pneumopericardium as onset symptom of fistulizing oesophageal cancer.

PMID- 29373661
TI  - Macrophage Migration Inhibitory Factor and microRNA-451a in Response to
      Mindfulness-based Therapy or Treatment as Usual in Patients with Depression,
      Anxiety, or Stress and Adjustment Disorders.
AB  - Background: Macrophage migration inhibitory factor is a proinflammatory cytokine
      that has been associated with various psychiatric disorders. MicroRNA-451a can
      directly target macrophage migration inhibitory factor and downregulate its
      expression in cells. However, the role of macrophage migration inhibitory factor
      and microRNA-451a in psychiatric patients treated with psychotherapeutic
      interventions is unknown. In this study, our aim was to investigate levels of
      macrophage migration inhibitory factor and its regulating microRNA-451a in
      patients with depression, anxiety, or stress and adjustment disorders who
      underwent mindfulness-based therapy or treatment as usual. Methods: A total of
      168 patients with psychiatric disorders were included from a randomized
      controlled trial that compared mindfulness-based therapy with treatment as usual.
      Plasma levels of macrophage migration inhibitory factor and microRNA-451a were
      measured at baseline and after the 8-week follow-up using Luminex assay and qPCR.
      Results: Macrophage migration inhibitory factor levels decreased significantly in
      patients posttreatment, whereas microRNA-451a levels showed a nonsignificant
      change. Macrophage migration inhibitory factor levels were inversely associated
      with microRNA-451a expression levels at baseline (beta=-0.04, P=.008). The change
      in macrophage migration inhibitory factor levels (follow-up levels minus baseline
      levels) was associated with the change in microRNA-451a (follow-up levels minus
      baseline levels) (beta=-0.06, P < .0001). The change in either macrophage
      migration inhibitory factor or microRNA-451a was not associated with improvement
      in psychiatric symptoms. Conclusion: We demonstrate that the levels of macrophage
      migration inhibitory factor decreased after psychotherapeutic interventions in
      patients with psychiatric disorders. However, this reduction was not associated
      with an improvement in psychiatric symptoms in response to the treatment. We also
      found an association between macrophage migration inhibitory factor and its
      regulating microRNA. However, this association needs to be further examined in
      future studies.

PMID- 29373663
TI  - Plant architecture and foliar senescence impact the race between wheat growth and
      Zymoseptoria tritici epidemics.
AB  - Background and Aims: In order to optimize crop management in innovative
      agricultural production systems, it is crucial to better understand how plant
      disease epidemics develop and what factors influence them. This study explores
      how canopy growth, its spatial organization and leaf senescence impact
      Zymoseptoria tritici epidemics. Methods: We used the Septo3D model, an epidemic
      model of Septoria tritici blotch (STB) coupled with a 3-D virtual wheat
      structural plant model (SPM). The model was calibrated and evaluated against
      field experimental data. Sensitivity analyses were performed on the model to
      explore how wheat plant traits impact the interaction between wheat growth and Z.
      tritici epidemics. Key Results: The model reproduces consistently the effects of
      crop architecture and weather on STB progress on the upper leaves. Model
      sensitivity analyses show that the effects of plant traits on epidemics depended
      on weather conditions. The simulations confirm the known effect of increased stem
      height and stem elongation rate on limiting STB progress on upper leaves.
      Strikingly, the timing of leaf senescence is one of the most influential traits
      on simulated STB epidemics. When the green life span duration of leaves is
      reduced by early senescence, epidemics are strongly reduced. Conclusions: We
      introduce the notion of a 'race' for the colonization of emerging healthy host
      tissue between the growing canopy and the developing epidemics. This race is 2
      fold: (1) an upward race at the canopy scale where STB must catch the newly
      emerging leaves before they grow away from the spore sources; and (2) a local
      race at the leaf scale where STB must use the resources of its host before it is
      caught by leaf apical senescence. The results shed new light on the importance of
      dynamic interactions between host and pathogen.

PMID- 29373664
TI  - Opportunities to Improve Fluoroquinolone Prescribing in the United States for
      Adult Ambulatory Care Visits.
AB  - The Food and Drug Administration warned against fluoroquinolone use for
      conditions with effective alternative agents. An estimated 5.1% of adult
      ambulatory fluoroquinolone prescriptions were for conditions that did not require
      antibiotics, and 19.9% were for conditions where fluoroquinolones are not
      recommended first-line therapy. Unnecessary fluoroquinolone use should be
      reduced.

PMID- 29373665
TI  - Insights into radiographic investigations for headaches in general practice.
AB  - Background/Objective: Headaches present commonly in general practice, and doctors
      face uncertainties and pressures in dealing with them. This study identifies key
      characteristics of headaches investigated through head imaging, in the hope of
      strengthening existing guidelines. Method: A 7-year retrospective analysis of
      head imaging scans ordered for investigating headaches among patients aged >=18
      in an Australian general practice setting. Results: A total of 109 of the 517
      (21.1%) patients required head imaging, although 14 (2.7%) of these had repeat
      scans. Three-quarters were females, and most of the headaches were recurrent
      (56.9%), severe (62.4%) or had associated red flags (78.0%). Computed tomography
      (CT) and magnetic resonance imaging (MRI) were the only scans adopted (4:1 and
      1:1 for first and repeat scans, respectively). Twelve (11.0%) scans had findings
      likely to explain the headaches after the initial scans, with no difference in
      findings between diagnoses from CTs and MRIs (P = 0.41). Repeat scans offered no
      additional benefits, and roughly one in three patients were referred to third
      party carers (mostly neurologists). Females had more recurrent headaches (OR =
      2.63; CI = 1.09-6.35; P = 0.03). Patients with psycho-morbidities were less
      likely to have scan findings that explained their headaches (OR = 0.22; CI = 0.06
      0.88; P = 0.03), and, though not quite significant, were also more likely to
      undergo imaging (OR = 1.47; CI 0.96-2.27; P = 0.08). Conclusion: Significant
      intracranial findings were uncommon following imaging for headaches, and MRIs
      offer no advantages over CTs. Repeating head scans within 5 years offers no clear
      benefits. Psycho-morbidities should be considered when deciding the imaging
      needs, given the lesser chance of findings. Larger studies will help validate
      these findings.

PMID- 29373666
TI  - Identification of Odor Blend Used by Caenorhabditis elegans for Pathogen
      Recognition.
AB  - Animals have evolved specialized pathways to detect appropriate food sources and
      avoid harmful ones. Caenorhabditis elegans can distinguish among the odors of
      various species of bacteria, its major food source, but little is known about
      what specific chemical cue or combination of chemical cues C. elegans uses to
      detect and recognize different microbes. Here, we examine the strong innate
      attraction of C. elegans for the odor of the pathogenic bacterium, Serratia
      marcescens. This initial attraction likely facilitates ingestion and infection of
      the C. elegans host. Using solid-phase microextraction and gas chromatography
      coupled with mass spectrometry, we identify 5 volatile odors released by S.
      marcescens and identify those that are attractive to C. elegans. We use genetic
      methods to show that the amphid chemosensory neuron, AWCON, senses both S.
      marcescens-released 2-butanone and acetone and drives attraction to S.
      marcescens. In C. elegans, pairing a single odorant with food deprivation results
      in a reduced attractive response for that specific odor. We find that pairing the
      natural odor of S. marcescens with food deprivation results in a reduced
      attraction for the natural odor of S. marcescens and a similar reduced attraction
      for the synthetic blend of acetone and 2-butanone. This result indicates that
      only 2 odorants represent the more complex odor bouquet of S. marcescens.
      Although bacterial-released volatiles have long been known to be attractive to C.
      elegans, this study defines for the first time specific volatile cues that
      represent a particular bacterium to C. elegans.

PMID- 29373667
TI  - Experimental ex vivo lung perfusion with sevoflurane: effects on damaged donor
      lung grafts.
AB  - OBJECTIVES: Volatile anaesthetics can provide significant protection against
      reperfusion injury in various experimental settings. The aim of this study was to
      assess the potential of sevoflurane treatment, the most commonly used volatile
      anaesthetic in modern anaesthesia, in rat lungs donated after circulatory death
      and reconditioned in an ex vivo lung perfusion (EVLP) system. METHODS: Fifteen
      rats were sacrificed and divided into 3 groups. In the control and sevoflurane
      groups, the heart-lung blocks were exposed to 1 h of warm ischaemia and 2 h of
      cold ischaemia and were mounted on an EVLP circuit for 3 h, in the absence or in
      the presence of 2% sevoflurane. In the baseline group, heart-lung blocks were
      harvested immediately after euthanasia. Physiological data, lung nitro-oxidative
      stress, lactate dehydrogenase (LDH), expression of cytokines, oedema and
      histopathological findings were assessed during or post-EVLP. RESULTS: The
      sevoflurane group showed significantly reduced LDH (8.82 +/- 3.58 arbitrary unit
      vs 3.80 +/- 3.02 arbitrary unit, P = 0.03), protein carbonyl (1.17 +/- 0.44
      nmol?mg-1 vs 0.55 +/- 0.11 nmol?mg-1, P = 0.006), 3-nitrotyrosine (197.44 +/-
      18.47 pg?mg-1 vs 151.05 +/- 23.54 pg?mg-1, P = 0.004), cytokine-induced
      neutrophil chemoattractant factor 1 (1.17 +/- 0.32 ng?mg-1 vs 0.66 +/- 0.28 ng?mg
      1, P = 0.03) and tumour necrosis factor alpha (1.50 +/- 0.59 vs 0.59 +/- 0.38
      ng?mg-1, P = 0.02) when compared with the control group. In addition, sevoflurane
      lungs gained significantly less weight (0.72 +/- 0.09 g vs 0.72 +/- 0.09 g, P =
      0.044), had less perivascular oedema (0.58 +/- 0.09 vs 0.47 +/- 0.07, P = 0.036),
      and improved static pulmonary compliance (+0.215 ml?cmH2O-1, P = 0.003) and peak
      airways pressure (-1.33 cmH2O, P = 0.04) but similar oxygenation capacity (+1.61
      mmHg, P = 0.77) and pulmonary vascular resistances (+0.078 mmHg?min?ml-1, P =
      0.15) when compared with the control group. CONCLUSIONS: These findings suggest
      that the potential of sevoflurane in protecting the lungs donated after cardiac
      death and reconditioned using EVLP could improve the outcome of these lungs
      following subsequent transplantation.

PMID- 29373669
TI  - Corrigendum to: Incidence of infective endocarditis among patients considered at
      high risk.

PMID- 29373668
TI  - Pervasive Correlated Evolution in Gene Expression Shapes Cell and Tissue Type
      Transcriptomes.
AB  - The evolution and diversification of cell types is a key means by which animal
      complexity evolves. Recently, hierarchical clustering and phylogenetic methods
      have been applied to RNA-seq data to infer cell type evolutionary history and
      homology. A major challenge for interpreting this data is that cell type
      transcriptomes may not evolve independently due to correlated changes in gene
      expression. This nonindependence can arise for several reasons, such as common
      regulatory sequences for genes expressed in multiple tissues, that is,
      pleiotropic effects of mutations. We develop a model to estimate the level of
      correlated transcriptome evolution (LCE) and apply it to different data sets. The
      results reveal pervasive correlated transcriptome evolution among different cell
      and tissue types. In general, tissues related by morphology or developmental
      lineage exhibit higher LCE than more distantly related tissues. Analyzing new
      data collected from bird skin appendages suggests that LCE decreases with the
      phylogenetic age of tissues compared, with recently evolved tissues exhibiting
      the highest LCE. Furthermore, we show correlated evolution can alter patterns of
      hierarchical clustering, causing different tissue types from the same species to
      cluster together. To identify genes that most strongly contribute to the
      correlated evolution signal, we performed a gene-wise estimation of LCE on a data
      set with ten species. Removing genes with high LCE allows for accurate
      reconstruction of evolutionary relationships among tissue types. Our study
      provides a statistical method to measure and account for correlated gene
      expression evolution when interpreting comparative transcriptome data.

PMID- 29373670
TI  - General ion recombination effect in a liquid ionization chamber in high-dose-rate
      pulsed photon and electron beams.
AB  - Liquid ionization chambers (LICs) are highly sensitive to dose irradiation and
      have small perturbations because of their liquid-filled sensitive volume. They
      require a sensitive volume much smaller than conventional air-filled chambers.
      However, it has been reported that the collection efficiency has dependencies on
      the dose per pulse and the pulse repetition frequency of a pulsed beam. The
      purpose of this study was to evaluate in detail the dependency of the ion
      collection efficiency on the pulse repetition frequency. A microLion (PTW,
      Freiburg, Germany) LIC was exposed to photon and electron beams from a TrueBeam
      (Varian Medical Systems, Palo Alto, USA) linear accelerator. The pulse repetition
      frequency was varied, but the dose per pulse was fixed. A theoretical evaluation
      of the collection efficiency was performed based on Boag's theory. Linear
      correlations were observed between the frequency and the relative collection for
      all energies of the photon and electron beams. The decrease in the collected
      charge was within 1% for all the flattened photon and electron beams, and they
      were 1.1 and 1.8% for the 6 and 10 MV flattening filter-free photon beams,
      respectively. The theoretical ion collection efficiency was 0.990 for a 10 MV
      flattened photon beam with a dose rate of 3 Gy.min-1. It is suggested that the
      collected charge decreased because of the short time intervals of the beam pulse
      compared with the ion collection time. Thus, it is important to correctly choose
      the pulse repetition frequency, particularly when flattening filter-free mode is
      used for absolute dose measurements.

PMID- 29373671
TI  - Modeling the Phenology of Asian Citrus Psyllid (Hemiptera: Liviidae) in Urban
      Southern California: Effects of Environment, Habitat, and Natural Enemies.
AB  - Modeling can be used to characterize the effects of environmental drivers and
      biotic factors on the phenology of arthropod pests. From a biological control
      perspective, population dynamics models may provide insights as to when the most
      vulnerable pest life stages are available for natural enemies to attack. Analyses
      presented here used temperature and habitat dependent, instar-specific, discrete
      models to investigate the population dynamics of Asian citrus psyllid, Diaphorina
      citri Kuwayama (Hemiptera: Liviidae). This pest is the target of a classical
      biological control program with the parasitoid Tamarixia radiata (Waterston)
      (Hymenoptera: Eulophidae). The population trends of D. citri eggs, nymphs, and
      adults, citrus flush growth patterns, and T. radiata activity were monitored
      monthly on orange and lemon trees at 10 urban sites in southern California for a
      2-yr period. Cumulative D. citri egg, nymph, and adult days recorded at each
      site, were regressed against accumulated degree-days (DDs) to model the
      population dynamics of each development stage in relation to temperature. Using a
      biofix point of 1 January, the model predicted that 10% and 90% of eggs were laid
      by 198 and 2,255 DD, respectively. Populations of small and large D. citri nymphs
      increased slowly with 90% of the population recorded by 2,389 and 2,436 DD,
      respectively. D. citri adults were present year round with 10 and 90% of the
      population recorded by 95 and 2,687 DD, respectively. The potential implications
      of using DD models for optimizing inoculative releases of natural enemies, such
      as T. radiata into citrus habitat infested with D. citri, are discussed.

PMID- 29373673
TI  - A 17-Year-Old Boy With Right Face Palsy, Left Leg Weakness, and Lytic Skull-Bone
      Lesions.
AB  - Human T-cell lymphotropic virus (HTLV), an infection that is endemic in certain
      parts of Asia, Africa, and South America, has been associated with malignancy and
      neurological deficits. Here, we describe a pediatric patient with chronic HTLV-I
      infection who developed complications associated with HTLV-I (ie, adult T-cell
      leukemia/lymphoma and HTLV-I-associated myelopathy/tropical spastic paraparesis).
      To our knowledge, this presentation in a child has never been described. The
      patient underwent a bone marrow transplant and, at the time of this writing, was
      in remission. This case report highlights the fact that HTLV-related
      complications, previously expected to occur after decades of infection, also can
      occur in pediatric patients, particularly those who acquired HTLV-I perinatally.

PMID- 29373672
TI  - Global Trends in CD4 Cell Count at the Start of Antiretroviral Therapy:
      Collaborative Study of Treatment Programs.
AB  - Background: Early initiation of combination antiretroviral therapy (cART), at
      higher CD4 cell counts, prevents disease progression and reduces sexual
      transmission of human immunodeficiency virus (HIV). We describe the temporal
      trends in CD4 cell counts at the start of cART in adults from low-income, lower
      middle-income, upper-middle-income, and high-income countries (LICs, LMICs,
      UMICs, and HICs, respectively). Methods: We included HIV-infected individuals
      aged >=16 years who started cART between 2002 and 2015 in a clinic participating
      in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the
      Collaboration of Observational HIV Epidemiological Research in Europe (COHERE).
      Missing CD4 cell counts at the start of cART were estimated through multiple
      imputation. Weighted mixed-effect models were used to smooth trends in median CD4
      cell counts. Results: A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs,
      and 19 HICs were included. Overall, the modeled median CD4 cell count at the
      start of cART increased from 2002 to 2015, from 78/uL (95% confidence interval,
      58-104/uL) to 287/uL (250-328/uL) in LICs, from 99/uL (71-140/uL) to 234/uL (192
      285/uL) in LMICs, from 71/uL (49-104/uL) to 311/uL (255-379/uL) in UMICs, and
      from 161/uL (143-181/uL) to 327/uL (286-372/uL) in HICs. In LICs, LMICs, and
      UMICs, the increase was more pronounced in women; in HICs, the opposite was
      observed. Conclusions: Median CD4 cell counts at the start of cART increased in
      all income groups, but generally remained below 350/MUL in 2015. Substantial
      additional efforts and resources are required to achieve earlier diagnosis,
      linkage to care, and initiation of cART.

PMID- 29373674
TI  - Two decades of blaVIM-2-producing Pseudomonas aeruginosa dissemination: an
      interplay between mobile genetic elements and successful clones.
AB  - Objectives: Information on clonal lineages and genetic platforms involved in the
      mobilization of carbapenemases between Pseudomonas aeruginosa strains in Portugal
      is scarce. Here, we outline the genetic drivers contributing to the occurrence of
      blaVIM-2-producing P. aeruginosa over two decades. Methods: A collection of
      carbapenem-resistant P. aeruginosa clinical isolates (n = 263, 1995-2014) was
      screened for carbapenemase production by Blue-Carba and PCR. Antimicrobial
      susceptibility testing was performed according to EUCAST and clonal analysis by
      MLST. Nine isolates representing different integrons and STs were selected for
      WGS, followed by bioinformatics. Results: Twenty-seven blaVIM-2-producing P.
      aeruginosa belonging to 10 STs were identified, with ST179 and ST111 being the
      most prevalent and persistent clones. blaVIM-2 was associated with seven class I
      integrons frequently co-harbouring aminoglycoside resistance genes. In58 was
      commonly identified, followed by derivatives and In100. blaVIM-2-harbouring
      transposons of the Tn3 and Tn402 families were linked to different plasmids or
      integrative conjugative elements of the clc family. Conclusions: The
      dissemination of blaVIM-2 carrying integrons is associated with a complex
      interplay between different mobile genetic elements, including the overlooked
      integrative conjugative elements, and successful spread of particular clones.

PMID- 29373675
TI  - Zoonotic Infection With Pigeon Paramyxovirus Type 1 Linked to Fatal Pneumonia.
AB  - The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1)
      infection in humans are poorly known. We performed virological, pathological, and
      epidemiological analyses of a Dutch case, and compared the results with those of
      a US case. Both infections occurred in transplant patients under
      immunosuppressive therapy and caused fatal respiratory failure. Both virus
      isolates clustered with PPMV-1, which has pigeons and doves as reservoir.
      Experimentally inoculated pigeons became infected and transmitted the virus to
      naive pigeons. Both patients were likely infected by contact with infected
      pigeons or doves. Given the large populations of feral pigeons with PPMV-1
      infection in cities, increasing urbanization, and a higher proportion of
      immunocompromised individuals, the risk of severe human PPMV-1 infections may
      increase. We recommend testing for avian paramyxovirus type 1, including PPMV-1,
      in respiratory disease cases where common respiratory pathogens cannot be
      identified.

PMID- 29373676
TI  - The Precarity of Older Adults Living Alone With Cognitive Impairment.
AB  - Purpose of the Study: To examine the lived experience of older adults living
      alone with cognitive impairment to better understand their needs and concerns.
      Based on our previous work suggesting that older adults living alone often
      experience a sense of precarity, we were interested in exploring this construct
      in older adults living alone with a diagnosis of cognitive impairment. The notion
      of precarity points to the uncertainty deriving from coping with cumulative
      pressures while trying to preserve a sense of independence. Design and Methods:
      This is a qualitative study of 12 adults aged 65 and older living alone with
      cognitive impairment. Six participants had a diagnosis of Alzheimer's disease; 6
      had a diagnosis of mild cognitive impairment. Participants' lived experiences
      were elicited through 40 ethnographic interviews and participant observation in
      their homes. Using a qualitative content analysis approach, interview transcripts
      and fieldnotes were analyzed to identify codes and themes. Results: Qualitative
      analysis of transcripts revealed three themes. Theme 1 described the distress
      stemming from the uncertainty of having cognitive impairment that has an
      unpredictable course. Theme 2 drew attention to the tendency of participants to
      feel responsible for managing their cognitive impairment. Theme 3 described the
      pressures stemming from the lack of appropriate services to support independent
      living for persons with cognitive impairment. Implications: These 3 themes all
      pointed to facets of precarity. Findings also suggest the dearth of programs to
      support older adults living alone with cognitive impairment and the need to
      develop novel programs and interventions.

PMID- 29373677
TI  - Pathway involving the N155H mutation in HIV-1 integrase leads to dolutegravir
      resistance.
AB  - Background: Dolutegravir, an integrase strand-transfer inhibitor (STI), shows a
      high genetic barrier to resistance. Dolutegravir is reported to be effective
      against viruses resistant to raltegravir and elvitegravir. In this study, we
      report the case of a patient treated with dolutegravir monotherapy. Failure of
      dolutegravir treatment was observed concomitant with the appearance of N155H
      K211R-E212T mutations in the integrase (IN) gene in addition to the polymorphic
      K156N mutation that was present at baseline in this patient. Methods: The impact
      of N155H-K156N-K211R-E212T mutations was studied in cell-free, culture-based
      assays and by molecular modelling. Results: Cell-free and culture-based assays
      confirm that selected mutations in the patient, in the context of the polymorphic
      mutation K156N present at the baseline, lead to high resistance to dolutegravir
      requiring that the analysis be done at timepoints longer than usual to properly
      reveal the results. Interestingly, the association of only N155H and K156N is
      sufficient for significant resistance to dolutegravir. Modelling studies showed
      that dolutegravir is less stable in IN/DNA complexes with respect to the WT
      sequence. Conclusions: Our results indicate that the stability of STI IN/DNA
      complexes is an important parameter that must be taken into account when
      evaluating dolutegravir resistance. This study confirms that a pathway including
      N155H can be selected in patients treated with dolutegravir with the help of the
      polymorphic K156N that acts as a secondary mutation that enhances the resistance
      to dolutegravir.

PMID- 29373679
TI  - Mechanistic peculiarities of activation-induced mobilization of cytotoxic
      effector proteins in human T cells.
AB  - It is widely accepted that cytotoxic T and NK cells store effector proteins
      including granzymes, perforin and Fas ligand (FasL) in intracellular granules,
      often referred to as secretory lysosomes. Upon target cell encounter, these
      organelles are transported to the cytotoxic immunological synapse, where they
      fuse with the plasma membrane to release the soluble effector molecules and to
      expose transmembrane proteins including FasL on the cell surface. We previously
      described two distinct species of secretory vesicles in T and NK cells that
      differ in size, morphology and protein loading, most strikingly regarding FasL
      and granzyme B. We now show that the signal requirements for the mobilization of
      one or the other granule also differ substantially. We report that prestored FasL
      can be mobilized independent of extracellular Ca2+, whereas the surface exposure
      of lysosome-associated membrane proteins (Lamps; CD107a and CD63) and the release
      of granzyme B are calcium-dependent. The use of selective inhibitors of actin
      dynamics unequivocally points to different transport mechanisms for individual
      vesicles. While inhibitors of actin polymerization/dynamics inhibit the surface
      appearance of prestored FasL, they increase the activation-induced mobilization
      of CD107a, CD63 and granzyme B. In contrast, inhibition of the actin-based motor
      protein myosin 2a facilitates FasL-, but impairs CD107a-, CD63- and granzyme B
      mobilization. From our data, we conclude that distinct cytotoxic effector
      granules are differentially regulated with respect to signaling requirements and
      transport mechanisms. We suggest that a T cell might 'sense' which effector
      proteins it needs to mobilize in a given context, thereby increasing efficacy
      while minimizing collateral damage.

PMID- 29373678
TI  - Design and evaluation of a novel flavonoid-based radioprotective agent utilizing
      monoglucosyl rutin.
AB  - In this study, three novel flavonoid composite materials, created by combining an
      aglycone [quercetin (QUE), hesperetin (HES) or naringenin (NAR)] with
      monoglucosyl rutin (MGR), were designed to test for improved radioprotectivity
      compared with that provided by administration of MGR alone. Aglycone in the MGR
      composite state was highly soluble in water, compared with aglycone alone
      dissolved in dimethyl sulfoxide or distilled water. The antioxidant activity of
      the three flavonoid composites was as high as that of MGR only. Next, the
      cytotoxicity test after 30 min treatment of an MGR composite showed a clear
      reduction in cell viability and suggested that a rapid introduction of aglycone
      into cells had taken place. In addition, QUE/MGR and HES/MGR composites strongly
      scavenged intracellular reactive oxygen species (ROS) induced by X-ray
      irradiation as well as MGR alone did. However, in the colony-formation assay
      using irradiated Chinese hamster ovary (CHO) cells, the HES/MGR composite showed
      a stronger radioprotective effect than MGR alone did, but the QUE/MGR composite
      showed no additional protective effect compared with the control. Furthermore, it
      was revealed that QUE and QUE/MGR composite treatment had the effect of reducing
      the glutathione (GSH) content in cells, and that QUE showed a stronger inhibition
      of PARP activity compared that of HES and NAR. Our data demonstrated that when
      designing a flavonoid composite as a radioprotective agent, it was necessary to
      select an appropriate aglycone, considering not only its antioxidant ability but
      also its inhibitory effect on cell recovery or DNA repair after radiation injury.

PMID- 29373680
TI  - Diversity of Leafhoppers (Hemiptera: Cicadellidae) Associated with Border Grasses
      and Maize During the Wet and Dry Seasons in Mexico.
AB  - Leafhoppers constitute one of the largest groups of pests causing damage to crops
      worldwide. Edge grasses, which are border crops (also known as border grasses),
      contain diverse plant species and maintain large populations of leafhoppers
      during the tropical dry and wet seasons. However, little is known about the
      diversity of leafhoppers on these grasses. The objective of this study was to
      characterize the diversity of leafhoppers on maize and on surrounding border
      grasses during the dry and wet seasons. Leafhopper adults were collected with a
      sweep net from border grasses during the dry season, when maize is absent. During
      the wet, maize-growing season, leafhoppers were collected in both the maize
      fields and their surrounding edge grasses. A highly diverse (H' = 1.97 +/- 2.03)
      leafhopper population was seen on the edge grasses during the dry season, and
      during the wet season, leafhopper diversity was higher in the edge grasses (H'=
      1.79 +/- 1.72) than in the maize fields themselves (H'= 1.67 +/- 1.12).
      Throughout the wet season, the most abundant leafhopper species in border grasses
      were Stirellus bicolor (Van Duzee) (Hemiptera: Cicadellidae), Graminella sonora
      (Ball) (Hemiptera: Cicadellidae), and Balclutha incisa (Matsumura) (Hemiptera:
      Cicadellidae), whereas Dalbulus maidis (DeLong) (Hemiptera: Cicadellidae) was the
      most abundant species in maize fields. All of these species were from the
      subfamily Deltocephalinae. Canonical Component Analysis showed that leafhopper
      abundance of Sibovia compta (Fowler) (Hemiptera: Cicadellidae), Graphocephala
      aurolineata (Fowler) (Hemiptera: Cicadellidae), D. maidis, and S. bicolor was
      associated with abiotic factors such as relative humidity, soil moisture,
      temperature, and pluvial precipitation. Nevertheless, for most leafhopper
      species, abundances were not significantly correlated with the abiotic variables
      measured.

PMID- 29373682
TI  - The impact of adenotonsillectomy on the dentofacial development of obstructed
      children.

PMID- 29373681
TI  - How equitable is social franchising? Case studies of three maternal healthcare
      franchises in Uganda and India.
AB  - Substantial investments have been made in clinical social franchising to improve
      quality of care of private facilities in low- and middle-income countries but
      concerns have emerged that the benefits fail to reach poorer groups. We assessed
      the distribution of franchise utilization and content of care by socio-economic
      status (SES) in three maternal healthcare social franchises in Uganda and India
      (Uttar Pradesh and Rajasthan). We surveyed 2179 women who had received antenatal
      care (ANC) and/or delivery services at franchise clinics (in Uttar Pradesh only
      ANC services were offered). Women were allocated to national (Uganda) or state
      (India) SES quintiles. Franchise users were concentrated in the higher SES
      quintiles in all settings. The percent in the top two quintiles was highest in
      Uganda (over 98% for both ANC and delivery), followed by Rajasthan (62.8% for
      ANC, 72.1% for delivery) and Uttar Pradesh (48.5% for ANC). The percent of
      clients in the lowest two quintiles was zero in Uganda, 7.1 and 3.1% for ANC and
      delivery, respectively, in Rajasthan and 16.3% in Uttar Pradesh. Differences in
      SES distribution across the programmes may reflect variation in user fees, the
      average SES of the national/state populations and the range of services covered.
      We found little variation in content of care by SES. Key factors limiting the
      ability of such maternal health social franchises to reach poorer groups may
      include the lack of suitable facilities in the poorest areas, the inability of
      the poorest women to afford any private sector fees and competition with free or
      even incentivized public sector services. Moreover, there are tensions between
      targeting poorer groups, and franchise objectives of improving quality and
      business performance and enhancing financial sustainability, meaning that middle
      income and poorer groups are unlikely to be reached in large numbers in the
      absence of additional subsidies.

PMID- 29373683
TI  - Aortic elongation in aortic aneurysm and dissection: the Tubingen Aortic
      Pathoanatomy (TAIPAN) project.
AB  - OBJECTIVES: To study the lengths and diameters of aortic segments in healthy and
      diseased aortas and to assess the role of aortic elongation in Type A aortic
      dissection (TAD) prediction. METHODS: Ectasia and aneurysm were defined by
      ascending aorta diameters of 45-54 mm and >=55 mm, respectively. Computed
      tomography angiography studies of 256 healthy, 102 ectasia, 38 aneurysm, 17 pre
      TAD and 166 TAD aortas were analysed using curved multiplanar reformats. RESULTS:
      The study groups were structurally equal. The diameter of the ascending aorta was
      35 mm in the control group and was larger (P < 0.001) in the pre-TAD (43 mm) and
      TAD (56 mm) groups. The length of the ascending aorta from the aortic annulus to
      the brachiocephalic trunk was 92 mm in the control group, 113 mm in the ectasia
      group, 120 mm in the aneurysm group and 111 mm and 118 mm in the pre-TAD and TAD
      groups (all P < 0.001 compared with the control group). An ascending aorta length
      of 120 mm was exceeded in 2% of the control group, 31% of the ectasia group, 50%
      of the aneurysm group, 24% of the pre-TAD group and 48% of the TAD group. The
      correlation between the diameter and the length of the ascending aorta was r =
      0.752; therefore, both parameters must be examined separately. A score
      considering both parameters identified 23.5% of pre-TAD patients, significantly
      more than the diameter alone, and 31.4% of ectasia aortas were elongated.
      CONCLUSIONS: Patients with ectatic (45-54 mm diameter) and elongated (>=120 mm)
      ascending aortas represent a high-risk subpopulation for TAD.

PMID- 29373685
TI  - Phytosphingosine is a novel activator of GPR120.
AB  - GPR120 is a receptor for long chain fatty acids and is expressed in small
      intestinal endocrine cells, L cells and adipose tissue. Activation of GPR120
      promotes the secretion of incretin GLP-1, which is known to have effects on anti
      metabolic syndrome. As such, GPR120 is a potential target of pharmaceuticals for
      type II diabetes. In this study, we performed ligand-screening for GPR120 on
      glycero- and sphingo-type lipids and their derivatives using a Transforming
      Growth Factor alpha-shedding assay. We found that phytosphingosine (PHS)
      activates GPR120 in a manner comparable to the natural ligand alpha-linolenic
      acid (ALA) and superior to that of the synthetic ligand GW9508. The IC50 value of
      PHS was 33.4 MUM, of ALA was 31.0 MUM and of GW9508 was 41.7 MUM. Additionally,
      PHS-induced activation of GPR120 was inhibited by the specific antagonist AH7614.
      Many of the natural or synthetic ligands found thus far are compounds with
      carboxyl groups. However, PHS does not possess a carboxyl group, suggesting that
      its manner of interaction with GPR120 may be significantly different from that of
      other ligands. Since PHS is rich in the plasma membrane of yeast, our results
      imply that PHS found in fermented food could have effects on anti-diabetes
      through activation of GPR120.

PMID- 29373684
TI  - The effects of dietary sulfur amino acids on growth performance, intestinal
      morphology, enzyme activity, and nutrient transporters in weaning piglets.
AB  - Early weaning results in intestinal dysfunction in piglets, while sulfur amino
      acids (SAA) are involved in improving intestinal functions. We tested a
      hypothesis that dietary supplementation with SAA can improve intestinal functions
      of weaning piglets and analyzed the effects of different dietary SAA levels on
      intestinal functions. A total of 80 piglets (Duroc * Landrace * Yorkshire) were
      weaned at 21 d of age and randomly assigned to one of the five diets that
      contained 0.53%, 0.63%, 0.74%, 0.85%, or 0.96% SAA, which corresponded to 70%,
      85%, 100%, 115%, or 130% of the SAA:Lys ratio recommended by the National
      Research Council (2012). The 14 d feeding experiment involved 16 pens per diet
      and one piglet per pen. Eight randomly selected piglets from each treatment were
      euthanized for tissue sampling on day 7 and 14 post weaning. Supplementation with
      SAA led to a rise over time in G:F (linear, P = 0.001; quadratic, P = 0.001).
      Between day 0 and 14 of treatment, the jejunal crypt depth decreased (linear, P =
      0.018; quadratic, P = 0.015), while that of the duodenal villus (linear, P =
      0.049) and ileal villus width (linear, P = 0.029; quadratic, P = 0.034)
      increased. The activities of jejunal alkaline phosphatase (ALP) were
      quadratically increased (P = 0.040) from day 0 to 14 due to dietary SAA. Dietary
      SAA also elevated the activities of jejunal lactase (linear, P = 0.003;
      quadratic, P = 0.004), jejunal sucrase (linear, P = 0.032; quadratic, P = 0.027),
      and jejunal contents of glutathione (GSH) from day 0 to 7, as well as the
      activity of jejunal maltase (linear, P = 0.014; quadratic, P = 0.001) between day
      0 and 14. During the first wk, dietary SAA linearly increased the amounts of
      intestinal-type fatty acid-binding protein (I-FABP) (P = 0.048) and SGLT-1 (P =
      0.021) and linearly decreased the amount of GLUT2 (P = 0.029) proteins in the
      jejunum. The abundance of jejunal I-FABP (P = 0.044) and PEPT1 (P = 0.049)
      protein linearly increased from day 0 to 14 in response to this supplementation.
      These findings indicate that there is a dose-dependent response to dietary SAA on
      feed efficiency and intestinal parameters of weanling pigs.

PMID- 29373686
TI  - Protective Effectiveness of Inactivated Hantavirus Vaccine Against Hemorrhagic
      Fever With Renal Syndrome.
AB  - As there is no effective treatment against hemorrhagic fever with renal syndrome
      (HFRS), the development of effective vaccine is important. An inactivated
      hantavirus vaccine (IHV) has been used in Korea, but there has been controversy
      regarding its effectiveness. We conducted a case-control study to evaluate the
      vaccine effectiveness (VE) of IHV against HFRS in the Korean military. Unadjusted
      and adjusted VEs of IHV were 59.1% and 58.9%, respectively. VE was higher in
      divisions with high incidence of HFRS (unadjusted VE, 71.4%; adjusted VE, 78.7%).
      Our study demonstrated the moderate effectiveness of IHV in high-risk populations
      residing in endemic area.

PMID- 29373687
TI  - Substituting Abacavir for Stavudine in Children Who Are Virally Suppressed
      Without Lipodystrophy: Randomized Clinical Trial in Johannesburg, South Africa.
AB  - Objectives: Abacavir has replaced stavudine in antiretroviral therapy (ART)
      regimens because it has largely been phased out as a result of toxicity concerns;
      this loss has reduced further the already-limited drug options for children. Few
      data regarding virologic and metabolic outcomes among children who undergo
      substitution of stavudine exist. We evaluated the effects of preemptive
      substitution of abacavir for stavudine in children initially without
      lipodystrophy and virally suppressed on a stavudine-containing regimen. Methods:
      At Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa, virally
      suppressed human immunodeficiency virus (HIV)-infected children >=36 months of
      age without lipodystrophy were randomly assigned to continue taking stavudine as
      part of their ART regimen (n = 106) or to have abacavir substituted for stavudine
      (n = 107). The children were followed for 56 weeks after randomization in the
      context of a larger trial of treatment options for ART-experienced children.
      Results: The mean age of the children was 4.3 years, and the mean duration of ART
      before random assignment was 3.5 years. No differences in virological outcomes,
      CD4 response, growth, or dyslipidemia were noted between the stavudine and
      abacavir groups. By 56 weeks, children in the abacavir group had less clinically
      detected lipodystrophy (4.7% vs 16%, respectively), a higher proportion of leg
      fat relative to total fat (0.243 vs 0.230, respectively; P = .006), and a lower
      trunk/leg-skinfold ratio (0.547 vs 0.569, respectively; P = .003) than the
      children in the stavudine group. Conclusion: Substituting abacavir for stavudine
      did not compromise virological response to treatment and was associated with
      significantly less lipodystrophy. These results support recommendations that
      favor abacavir in this population.

PMID- 29373688
TI  - Compromised JMJD6 Histone Demethylase Activity Affects VHL Gene Repression in
      Preeclampsia.
AB  - Context: The von Hippel Lindau (VHL) protein is a key executor of the cellular
      hypoxic response that is compromised in preeclampsia, a serious disorder
      complicating 5% to 7% of pregnancies. To date, the mechanisms controlling VHL
      gene expression in the human placenta remain elusive. Objective: We examined VHL
      epigenetic regulation in normal pregnancy and in preeclampsia, a pathology
      characterized by placental hypoxia. Design, Setting, and Participants: Placentae
      were obtained from early-onset preeclampsia (n = 56; <34 weeks of gestation) and
      late-onset preeclampsia (n = 19; >=34 weeks of gestation). Placentae from healthy
      normotensive age-matched preterm control (n = 43) and term control (n = 23)
      pregnancies were included as controls. Main Outcome Measure(s): We measured the
      activity of Jumonji domain containing protein 6 (JMJD6), a ferrous iron (Fe2+)-
      and oxygen-dependent histone demethylase, and examined its function in the
      epigenetic control of VHL. Results: JMJD6 regulates VHL gene expression in the
      human placenta. VHL downregulation in preeclampsia is dependent on decreased
      JMJD6 demethylase activity due to hypoxia and reduced Fe2+ bioavailability.
      Chromatin immunoprecipitation assays revealed decreased association of JMJD6 and
      its histone targets with the VHL promoter. Findings in preeclampsia were
      corroborated in a murine model of pharmacological hypoxia using FG-4592.
      Placentae from FG-4592-treated mice exhibited reduced VHL levels, accompanied by
      placental morphological alterations and reduced pup weights. Notably, Fe2+
      supplementation rescued JMJD6 histone demethylase activity in histone from E-PE
      and FG-4592-treated mice. Conclusions: Our study uncovers epigenetic regulation
      of VHL and its functional consequences for altered oxygen and iron homeostasis in
      preeclampsia.

PMID- 29373689
TI  - Central Line-Associated Mucor velutinosus Bloodstream Infection in an
      Immunocompetent Pediatric Patient.
AB  - We report here the isolation of Mucor velutinosus from multiple blood cultures
      performed on samples from Broviac catheters and culture of a Broviac insertion
      site wound sample from a 6-year-old boy with a history of intestinal failure
      secondary to chronic intestinal pseudo-obstruction, parenteral nutrition, and
      jejunostomy tube dependence. Examination of a slide from the culture revealed the
      presence of wide nonseptate hyphae with sporangiophores, columella, and
      chlamydospores. The fungal isolate was sent to the National Institutes of Health
      for further evaluation and was identified as Mucor velutinosus by matrix-assisted
      laser desorption ionization-time-of-flight mass spectrometry and genomic
      sequencing. The patient was treated successfully with intravenous amphotericin B
      and prompt removal of his central line. To the best of our knowledge, this is the
      first case of M velutinosus bloodstream infection in a child without cancer.

PMID- 29373690
TI  - Novel Function of Cyclooxygenase-2: Suppressing Mycobacteria by Promoting
      Autophagy via the Protein Kinase B/Mammalian Target of Rapamycin Pathway.
AB  - In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2)
      expression considerably increases to defend the body against mycobacteria by
      regulating adaptive immunity and restoring the mitochondrial inner membrane.
      Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important
      bactericidal mechanism. However, the association between M. tuberculosis-induced
      COX-2 and autophagy-mediated antimycobacterial response has not been explored.
      Here, COX-2 expression silencing reduced the autophagy and bactericidal activity
      against intracellular M. tuberculosis, while COX-2 overexpression reversed the
      above effects. In addition, enhancement of bactericidal activity was suppressed
      by inhibiting autophagy in COX-2-overexpressing cells, indicating that COX-2
      accelerated mycobacterial elimination by promoting autophagy. Furthermore, the
      regulatory effects of COX-2 on autophagy were mediated by its catalytic products,
      which functioned through inhibiting the protein kinase B/mammalian target of
      rapamycin pathway. Thus, COX-2 contributes to host defense against mycobacterial
      infection by promoting autophagy, establishing the basis for development of novel
      therapeutic agents against tuberculosis by targeting COX-2.

PMID- 29373691
TI  - Recombination of plasmids in a carbapenem-resistant NDM-5-producing clinical
      Escherichia coli isolate.
AB  - Objectives: To investigate the genetic features of five plasmids recovered from
      an NDM-5-producing clinical Escherichia coli strain, BJ114, and to characterize
      the plasmid recombination event that occurred during the conjugation process.
      Methods: The genetic profiles of the five plasmids were determined by PCR,
      conjugation, S1-PFGE, Southern hybridization and WGS analysis. Plasmid sequences
      were analysed with various bioinformatic tools. Results: Complete sequences of
      five plasmids were obtained. Two small plasmids, pBJ114-141 and pBJ114-46, were
      speculated to have recombined into a large fusion plasmid, pBJ114T-190. When
      conjugated to other E. coli strains, some of the fusion plasmids were able to be
      resolved into the original two single plasmids. A non-conjugative plasmid, pBJ114
      96, exhibited a high degree of sequence identity with the phage P7-like plasmid
      as well as an mcr-1-bearing plasmid. Another plasmid, pBJ114-78, was found to
      contain multidrug resistance genes and various mobile elements. Conclusions: The
      fusion plasmid recoverable from the transconjugant was found to be generated as a
      result of a recombination event that occurred upon interaction between a blaNDM-5
      carrying plasmid and another plasmid present in the parental strain. Such
      recombination events presumably play a potential role in the dissemination of the
      blaNDM genes among different plasmids and pathogenic bacterial strains.

PMID- 29373692
TI  - Comment on: Failure of rivaroxaban to prevent thrombosis in four patients with
      anti-phospholipid syndrome: reply.

PMID- 29373693
TI  - Lung-Derived Exosomal miR-483-3p Regulates the Innate Immune Response to
      Influenza Virus Infection.
AB  - Exosomes regulate cell-cell communication by transferring functional proteins and
      RNAs between cells. Here, to clarify the function of exosomes during influenza
      virus infection, we characterized lung-derived exosomal microRNAs (miRNAs). Among
      the detected miRNAs, miR-483-3p was present at high levels in bronchoalveolar
      lavage fluid (BALF) exosomes during infection of mice with various strains of
      influenza virus, and miR-483-3p transfection potentiated gene expression of type
      I interferon and proinflammatory cytokine upon viral infection of MLE-12 cells.
      RNF5, a regulator of the RIG-I signaling pathway, was identified as a target gene
      of miR-483-3p. Moreover, we found that CD81, another miR-483-3p target, functions
      as a negative regulator of RIG-I signaling in MLE-12 cells. Taken together, this
      study indicates that BALF exosomal miRNAs may mediate the antiviral and
      inflammatory response to influenza virus infection.

PMID- 29373694
TI  - Impact of antiretroviral resistance and virological failure on HIV-1
      informational entropy.
AB  - Objectives: The present study investigated the relationship between genomic
      variability and resistance of HIV-1 sequences in protease (PR) and reverse
      transcriptase (RT) regions of the pol gene. In addition, we analysed the
      resistance among 651 individuals presenting antiretroviral virological failure,
      from 2009 to 2011, in the state of Sao Paulo, Brazil. Methods: The genomic
      variability was quantified by using informational entropy methods and the
      relationship between resistance and replicative fitness, as inferred by the
      residual viral load and CD4+ T cell count. Results: The number of antiretroviral
      schemes is related to the number of resistance mutations in the HIV-1 PR (alpha =
      0.2511, P = 0.0003, R2 = 0.8672) and the RT (alpha = 0.7892, P = 0.0001, R2 =
      0.9141). Increased informational entropy rate is related to lower levels of HIV-1
      viral loads (alpha = -0.0121, P = 0.0471, R2 = 0.7923), lower levels of CD4+ T
      cell counts (alpha = -0.0120, P = 0.0335, R2 = 0.8221) and a higher number of
      antiretroviral resistance-related mutations. Conclusions: Less organized HIV
      genomes as inferred by higher levels of informational entropy relate to less
      competent host immune systems, lower levels of HIV replication and HIV genetic
      evolution as a consequence of antiretroviral resistance.

PMID- 29373695
TI  - Determination of Organophosphorous Pesticides in Blood Using Microextraction in
      Packed Sorbent and Gas Chromatography-Tandem Mass Spectrometry.
AB  - The aim of our work was to develop a method for the determination of six
      organophosphorous pesticides (Ops) (azynphos-ethyl (AZP), diazinon (DZN),
      chlorpyrifos (CLP), chlorfenvinfos (CLF), parathion-ethyl (PRT) and quinalphos
      (QLP)) in whole blood using microextraction by packed sorbent (MEPS) and analysis
      by gas chromatography-tandem mass spectrometry (GC-MS/MS). The optimization of
      the MEPS procedure was performed using a design of experiments (DOE) approach,
      assessing different factors that significantly affected the extraction
      efficiency. Ultimately, the number of sample strokes, wash volume, percentage of
      2-propanol in the wash solvent and the number of elution strokes were
      successfully optimized using a response surface methodology (RSM). The developed
      and optimized method was fully validated according to international guidelines.
      Linearity was established from 2.5 to 50 MUg/mL for AZP and from 0.5 to 50 MUg/mL
      for the remaining compounds, with coefficients of determination (R2) higher than
      0.99 in all cases. The lower limit of quantification were 2.5 MUg/mL (AZP) and
      0.5 MUg/mL (remaining compounds). Recoveries ranged from 61% to 77%. Intra- and
      inter-day precision and accuracy were considered adequate according to the
      guidelines. This is the first method employing MEPS as a sample preparation
      procedure for the analysis of these OPs in whole blood.

PMID- 29373696
TI  - Immunogenicity and safety of pneumococcal vaccination in patients with systemic
      sclerosis.

PMID- 29373697
TI  - Azithromycin-resistant Neisseria gonorrhoeae spreading amongst men who have sex
      with men (MSM) and heterosexuals in New South Wales, Australia, 2017.
AB  - Objectives: To identify the genetic basis of resistance as well as to better
      understand the epidemiology of a recent surge in azithromycin-resistant Neisseria
      gonorrhoeae in New South Wales, Australia. Methods: Azithromycin-resistant N.
      gonorrhoeae isolates (n = 118) collected from 107 males, 10 females and 1
      transsexual between January and July 2017 were genotyped using a previously
      described iPLEX method. The results were compared with phenotypic resistance
      profiles and available patient data. Results: The iPLEX results revealed 10
      different N. gonorrhoeae genotypes (designated AZI-G1 to AZI-G10) of which three
      were responsible for the majority of infections; AZI-G10 (74.6%, 88 isolates; 87
      males and 1 transsexual), AZI-G4 (11.0%, 13 isolates; 7 males and 6 females) and
      AZI-G7 (6.8%, 8 isolates; 7 males and 1 female). The observed resistance was
      attributable to one of two different azithromycin resistance mechanisms; the 23S
      rRNA C2611T mutation was identified in 24% of isolates, whereas the majority of
      resistance (76%) was associated with a meningococcal-type mtrR variant.
      Additionally, one isolate was found to harbour both the 23S rRNA C2611T mutation
      and a type XXXIV mosaic penA sequence associated with cephalosporin resistance.
      Conclusions: These data indicate outbreaks of azithromycin-resistant gonococci
      amongst networks of MSM and heterosexuals in New South Wales. The results also
      provide further evidence that azithromycin may soon be an ineffective treatment
      option for gonococcal infection and highlight the urgent need to explore
      alternative therapies.

PMID- 29373698
TI  - Randomized Trial to Compare Smoking Cessation Rates of Snus, with and without
      Smokeless Tobacco Health-Related Information, and a Nicotine Lozenge.
AB  - Introduction: Nicotine replacement medications are moderately effective in
      increasing quit rates. However, some smokers reject such aids, suggesting the
      value of considering alternative options. Snus, a smokeless tobacco product with
      low nitrosamine content, could offer an alternative. This study compared smoking
      cessation rates for snus, with and without information about reduced risk
      relative to smoking, with a nicotine lozenge (without relative risk information).
      Methods: A randomized, open-label, multicenter clinical trial with 649 smokers,
      aged 21 to 65, who smoked at least 10 cigarettes per day for the past year and
      were motivated to quit smoking. Participants were followed for up to 12 months
      and were provided no counseling or support. Smoking cessation was analyzed as
      continuous smoking abstinence (no smoking following quit date) and repeated point
      prevalence abstinence (no smoking within past 7 days). Results: Abstinence rates
      did not differ significantly between snus and the nicotine lozenge -continuous
      abstinence did not differ at any timepoint, and point prevalence rates differed
      only at month 3, when the lozenge group showed higher abstinence rates (17.4%)
      than either of the two snus groups (snus alone: 8.7%; snus plus information:
      10.1%). Large percentages of participants used the products during the treatment
      period. Providing relative risk information to snus users did not affect snus
      use. The amount of use did not predict subsequent outcome. Adverse events were
      reported at similar rates across the three groups. Conclusions: Smoking cessation
      rates were comparable between snus and a nicotine lozenge, but success rates in
      this trial were low. Implications: This randomized trial of the nicotine lozenge,
      snus, or snus plus information on the relative risks of smokeless tobacco vs.
      smoking found comparable but low smoking cessation rates for all three groups at
      weeks 12, 26, and 52.  The one-time provision of relative risk information did
      not lead to greater snus use among those provided the information, suggesting no
      effect for this brief intervention.

PMID- 29373699
TI  - Characteristics and mechanism of apogeotropic central positional nystagmus.
AB  - Here we characterize persistent apogeotropic type of central positional
      nystagmus, and compare it with the apogeotropic nystagmus of benign paroxysmal
      positional vertigo involving the lateral canal. Nystagmus was recorded in 27
      patients with apogeotropic type of central positional nystagmus (22 with
      unilateral and five with diffuse cerebellar lesions) and 20 patients with
      apogeotropic nystagmus of benign paroxysmal positional vertigo. They were tested
      while sitting, while supine with the head straight back, and in the right and
      left ear-down positions. The intensity of spontaneous nystagmus was similar while
      sitting and supine in apogeotropic type of central positional nystagmus, but
      greater when supine in apogeotropic nystagmus of benign paroxysmal positional
      vertigo. In central positional nystagmus, when due to a focal pathology, the
      lesions mostly overlapped in the vestibulocerebellum (nodulus, uvula, and
      tonsil). We suggest a mechanism for apogeotropic type of central positional
      nystagmus based on the location of lesions and a model that uses the velocity
      storage mechanism. During both tilt and translation, the otolith organs can relay
      the same gravito-inertial acceleration signal. This inherent ambiguity can be
      resolved by a 'tilt-estimator circuit' in which information from the semicircular
      canals about head rotation is combined with otolith information about linear
      acceleration through the velocity-storage mechanism. An example of how this
      mechanism works in normal subjects is the sustained horizontal nystagmus that is
      produced when a normal subject is rotated at a constant speed around an axis that
      is tilted away from the true vertical (off-vertical axis rotation). We propose
      that when the tilt-estimator circuit malfunctions, for example, with lesions in
      the vestibulocerebellum, the estimate of the direction of gravity is erroneously
      biased away from true vertical. If the bias is toward the nose, when the head is
      turned to the side while supine, there will be sustained, unwanted, horizontal
      positional nystagmus (apogeotropic type of central positional nystagmus) because
      of an inappropriate feedback signal indicating that the head is rotating when it
      is not.

PMID- 29373700
TI  - The Role of KLRG1 in Human CD4+ T-Cell Immunity Against Tuberculosis.
AB  - Background: KLRG1 is a marker of terminally differentiated CD8+ T cells in viral
      infection, but its role in human Mycobacterium tuberculosis infection remains
      elusive. Methods: A set of cohorts of patients with tuberculosis was designed,
      and the expression profiles and functions of KLRG1+CD4+ T cells were determined
      with and without antibody blocking. Results: KLRG1 expression on CD4+ T cells was
      significantly increased in patients with active tuberculosis, compared with
      healthy controls and patients without tuberculosis. Upon M. tuberculosis-specific
      stimulation, the ability to secrete interferon gamma, interleukin 2, and tumor
      necrosis factor alpha was significantly greater in KLRG1-expressing CD4+ T cells
      than in their KLRG-negative counterparts and was accompanied by a decreased
      proportion of regulatory T cells and increased Akt signaling. However, KLRG1
      expressing CD4+ T cells had a shorter life-span, which was associated with a
      higher apoptosis rate but a similar proliferative response. Blockade of KLRG1
      signaling significantly enhanced interferon gamma and interleukin 2 secretion
      without affecting either cell apoptosis or multiplication. Addition of a specific
      Akt inhibitor prevented this increased cytokine response, implicating the Akt
      signaling pathway. Conclusions: Our study delineated the profile of KLRG1+CD4+ T
      cells in patients with tuberculosis and suggests that M. tuberculosis infection
      drives CD4+ T cells to acquire increased effector function in a terminally
      differentiated state, which is restrained by KLRG1 via KLRG1/Akt signaling
      pathway.

PMID- 29373701
TI  - Contextual factors influence work outcomes in employed patients with ankylosing
      spondylitis starting etanercept: 2-year results from AS@Work.
AB  - Objectives: The aim was to determine changes over time in work outcomes and
      investigate the predictive value of baseline personal and work-related factors on
      the evolution of work outcomes among employed patients with AS initiating
      etanercept. Methods: Employment status, absenteeism and presenteeism were
      assessed using the Work Productivity and Activity Impairment for AS questionnaire
      in a 24-month open-label, observational study (NCT01421303). The potential effect
      of baseline factors on work outcomes was analysed using predictive modelling (Cox
      regression and linear mixed models). Results: After 24 months, 11/75 (14.7%)
      patients had permanently withdrawn from employment (seven because of AS).
      Absenteeism and presenteeism decreased significantly within 6 months of
      etanercept treatment and remained stable thereafter. Predictive modelling
      indicated that male sex (hazard ratio = 0.18; 95% CI: 0.04, 0.85), (log) number
      of working hours per week (hazard ratio = 0.13; 95% CI: 0.03, 0.51) and the
      possibility of developing skills (hazard ratio = 0.42; 95% CI: 0.19, 0.91)
      positively influenced time in employment. Over time, lower absenteeism was
      significantly associated with the quality of contact with colleagues [coefficient
      (s.e.): -0.35 (0.10)] and importance of the job for quality of life [-0.49
      (0.17)], and higher absenteeism with current smoking [1.66 (0.44)] and change in
      job because of illness [1.51 (0.66)]. Over time, lower presenteeism was
      associated with male sex [-14.5 (2.64)], the possibility of postponing work [
      6.60 (2.73)], quality of contact with colleagues [-2.04 (0.96)] and >50 workers
      in the company [-7.65 (2.76)], and higher presenteeism with manual profession
      [8.41 (2.72)]. Conclusion: Contextual factors influence work outcomes over time
      and should not be ignored when aiming to improve work outcomes in patients with
      AS. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov,
      NCT01421303.

PMID- 29373702
TI  - Tissue-specific changes in apoplastic proteins and cell wall structure during
      cold acclimation of winter wheat crowns.
AB  - The wheat (Triticum aestivum L.) crown is the critical organ of low temperature
      stress survival over winter. In cold-acclimated crowns, ice formation in the
      apoplast causes severe tissue disruption as it grows at the expense of
      intracellular water. While previous crown studies have shown the vascular
      transition zone (VTZ) to have a higher freezing sensitivity than the shoot apical
      meristem (SAM), the mechanism behind the differential freezing response is not
      fully understood. Cooling cold-acclimated crowns to -10  degrees C resulted in an
      absence of VTZ tetrazolium chloride staining, whereas the temperatures at which
      50% of the SAM stained positive and 50% of plants recovered (LT50) were similar
      after cold acclimation for 21 (-16  degrees C) and 42 d (-20  degrees C) at 4 
      degrees C. Proteomic analysis of the apoplastic fluids identified dehydrins,
      vernalization-responsive proteins, and cold shock proteins preferentially
      accumulated in the SAM. In contrast, modifications to the VTZ centered on
      increases in pathogenesis-related proteins, anti-freeze proteins, and sugar
      hydrolyzing enzymes. Fourier transform infrared spectroscopy focal plane array
      analysis identified the biochemical modification of the cell wall to enhance
      methyl-esterified cross-linking of glucuronoarabinoxylans in the VTZ. These
      findings indicate that the SAM and VTZ express two distinct tissue-specific
      apoplastic responses during cold acclimation.

PMID- 29373703
TI  - Trajectories of Acute Diabetes-Specific Stress in Adolescents With Type 1
      Diabetes and Their Caregivers Within the First Year of Diagnosis.
AB  - Objectives: Our aims were to describe stress trajectories for newly diagnosed
      type 1 diabetes (T1D) in adolescents and their parents, explore whether
      resilience is associated with stress trajectories, and to examine the effects of
      stress trajectories on diabetes-specific outcomes. Methods: Fifty-nine youth aged
      10-18 years with newly diagnosed T1D and a primary caregiver were followed for 12
      months. Stress and resilience were assessed using questionnaires every 3 months,
      and diabetes-specific outcomes (self-care, quality of life, and hemoglobin A1C)
      at 6 and 12 months. Parent and adolescent stress trajectories were identified
      using semiparametric group-based modeling. Results: Four stress trajectories
      emerged for parents and three emerged for adolescents. Adolescent trajectories
      were stable throughout the 12 months, and those with stable low stress had the
      highest levels of resilience. Further, the stable low stress group had higher
      quality of life scores at 12-month postdiagnosis. In contrast, stress for parents
      changed considerably over the 12-month period, and trajectory groups did not
      associate with 12-month outcomes. Conclusions: Distinct patterns of stress
      emerged for both the adolescent and parent cohorts. Resilience at the time of
      diagnosis was particularly protective for adolescents. These results suggest that
      stress-reducing and resilience-promoting interventions for newly diagnosed
      adolescents with T1D may have potential to improve longer-term outcomes.

PMID- 29373704
TI  - Comment on: Failure of rivaroxaban to prevent thrombosis in four patients with
      anti-phospholipid syndrome.

PMID- 29373705
TI  - Trabecular Bone Score in Obese and Nonobese Subjects With Primary
      Hyperparathyroidism Before and After Parathyroidectomy.
AB  - Context: Obesity has been shown to be unfavorable to skeletal microarchitecture
      when assessed by trabecular bone score (TBS). The influence of adiposity on
      skeletal microstructure in primary hyperparathyroidism (PHPT) has not yet been
      evaluated. Objective: To investigate the effect of obesity on TBS and bone
      mineral density (BMD) in subjects with PHPT at baseline and through 2 years after
      parathyroidectomy. Design: Prospective observational study. Setting: Referral
      center. Patients or Other Participants: Thirty men and women with PHPT undergoing
      parathyroid surgery. Main Outcome Measures: TBS and BMD by dual-energy X-ray
      absorptiometry (DXA). Results: There were notable improvements in lumbar spine
      and femoral neck BMD in the obese (lumbar spine: 4.3 +/- 4.7%, femoral neck: 3.8
      +/- 6.6%; P < 0.05 for both) and nonobese subjects (lumbar spine: 3.8 +/- 5.6%,
      femoral neck 3.1 +/- 5.0%; P < 0.05 for both) but no marked change in TBS in
      either group at 24 months postparathyroidectomy. Obese subjects had fully
      degraded TBS values compared with the nonobese subjects, whose TBS values were
      minimally below normal throughout the study (baseline: 1.199 +/- 0.086 vs 1.327
      +/- 0.099, respectively; P = 0.003; 24 months: 1.181 +/- 0.061 vs 1.352 +/-
      0.114, respectively; P = 0.001), despite improvements in BMD. Conclusions: The
      detrimental effect of obesity on TBS, an index of bone quality, was demonstrated
      in subjects with PHPT. Obesity was associated with fully degraded skeletal
      microarchitecture as measured by TBS in PHPT, despite similar values in bone
      density by DXA compared with nonobese subjects. TBS values did not improve
      postparathyroidectomy in either obese or nonobese subjects.

PMID- 29373706
TI  - Maturation of the 90S pre-ribosome requires Mrd1 dependent U3 snoRNA and 35S pre
      rRNA structural rearrangements.
AB  - In eukaryotes, ribosome biogenesis requires folding and assembly of the precursor
      rRNA (pre-rRNA) with a large number of proteins and snoRNPs into huge RNA-protein
      complexes. In spite of intense genetic, biochemical and high-resolution cryo-EM
      studies in Saccharomyces cerevisiae, information about the structure of the 35S
      pre-rRNA is limited. To overcome this, we performed high-throughput SHAPE
      chemical probing on the 35S pre-rRNA within 90S pre-ribosomes. We focused our
      analyses on external (5'ETS) and internal (ITS1) transcribed spacers as well as
      the 18S rRNA region. We show that in the 35S pre-rRNA, the central pseudoknot is
      not formed and the central core of the 18S rRNA is in an open configuration but
      becomes more constrained in 20S pre-rRNA. The essential ribosome biogenesis
      protein Mrd1 influences the structure of the 18S rRNA region locally and is
      involved in organizing the central pseudoknot and surrounding structures. We
      demonstrate that U3 snoRNA dynamically interacts with the 35S pre-rRNA and that
      Mrd1 is required for disrupting U3 snoRNA base pairing interactions in the 5'ETS.
      We propose that the dynamic U3 snoRNA interactions and Mrd1 are essential for
      establishing the structure of the central core of 18S rRNA that is required for
      processing and 40S subunit function.

PMID- 29373708
TI  - Professor Adayapalam Tyagarajan Natarajan (1928-2017): a tribute.

PMID- 29373707
TI  - Cardiovascular and cerebrovascular comorbidities of juvenile dermatomyositis in
      US children: an analysis of the National Inpatient Sample.
AB  - Objective: JDM is associated with multiple potential risk factors for
      cardiovascular disease, including reduced heart rate variability,
      systolic/diastolic cardiac dysfunction, abnormal brachial artery reactivity and
      metabolic syndrome. However, little is known about cardiovascular risk in JDM. We
      sought to examine the association between JDM and cardiovascular risk factors and
      disease in US children. Methods: Data from the 2002-12 National Inpatient Sample
      was analysed, including ~20% of all US hospitalizations (n = 14 535 620
      paediatric hospitalizations). Results: JDM was significantly associated with 12
      of 13 comorbidities, including hypertension [survey logistic regression; crude
      odds ratio (95% CI): 22.25 (15.51, 31.92)], obesity [5.87 (3.44, 10.02)],
      uncomplicated diabetes [7.95 (4.21, 15.00)], lipid abnormalities [5.84 (2.77,
      12.31)], particularly lipodystrophy [151.08 (38.24, 596.86)], peripheral and
      visceral atherosclerosis [10.09 (3.70, 27.56)], late effects of cerebrovascular
      disease [15.49 (2.37, 101.43)], personal history of transient ischaemic attack
      and cerebral infarction [10.82 (2.46, 47.65)], pulmonary circulatory disorder
      [12.23 (2.59, 57.73)], arrhythmia [3.93 (2.80, 5.52)], bradycardia [4.22 (2.65,
      6.74)] and hypotension [2.62 (1.27, 5.39)]. Conclusions: There are significantly
      higher odds of cardiovascular and cerebrovascular comorbidities among inpatients
      with JDM, with adolescents, girls and racial/ethnic minorities being at highest
      risk.

PMID- 29373710
TI  - Smart Glasses for Neurosurgical Navigation by Augmented Reality.
AB  - BACKGROUND: Wearable devices with heads-up displays or smart glasses can overlay
      images onto the sight of the wearer. This technology has never been applied to
      surgical navigation. OBJECTIVE: To assess the applicability and accuracy of smart
      glasses for augmented reality (AR)-based neurosurgical navigation. METHODS: Smart
      glasses were applied to AR-based neurosurgical navigation. Three-dimensional
      computer graphics were created based on preoperative magnetic resonance images
      and visualized in see-through smart glasses. Optical markers were attached to the
      smart glasses and the patient's head for accurate navigation. Two motion capture
      cameras were used for registration and continuous monitoring of the location of
      the smart glasses in relation to the patient's head. After the accuracy was
      assessed with a phantom, this technique was applied in 2 patients with brain
      tumors located in the brain surface. RESULTS: A stereoscopic view by image
      overlay through the smart glasses was successful in the phantom and in both
      patients. Hands-free neuronavigation inside the operative field was available
      from any angles and distances. The targeting error in the phantom measured in 75
      points ranged from 0.2 to 8.1 mm (mean 3.1 +/- 1.9 mm, median 2.7 mm). The
      intraoperative targeting error between the visualized and real locations in the 2
      patients (measured in 40 points) ranged from 0.6 to 4.9 mm (mean 2.1 +/- 1.1 mm,
      median 1.8 mm). CONCLUSION: Smart glasses enabled AR-based neurosurgical
      navigation in a hands-free fashion. Stereoscopic computer graphics of targeted
      brain tumors corresponding to the surgical field were clearly visualized during
      surgery.

PMID- 29373709
TI  - Selection of external beam radiotherapy approaches for precise and accurate
      cancer treatment.
AB  - Physically precise external-beam radiotherapy (EBRT) technologies may not
      translate to the best outcome in individual patients. On the other hand, clinical
      considerations alone are often insufficient to guide the selection of a specific
      EBRT approach in patients. We examine the ways in which to compare different EBRT
      approaches based on physical, biological and clinical considerations, and how
      they can be enhanced with the addition of biophysical models and machine-learning
      strategies. The process of selecting an EBRT modality is expected to improve in
      tandem with knowledge-based treatment planning.

PMID- 29373711
TI  - Pioglitazone Therapy of PAX8-PPARgamma Fusion Protein Thyroid Carcinoma.
AB  - Context: A subset of thyroid carcinomas expresses an oncogenic paired box 8
      (PAX8) and peroxisome proliferator activated receptor gamma (PPARgamma) fusion
      protein (PPFP). The PPARgamma/PPFP ligand pioglitazone is highly therapeutic in a
      transgenic mouse model of PPFP thyroid carcinoma, but whether pioglitazone is
      therapeutic in patients with PPFP thyroid carcinoma is unknown. Case Description:
      Tumor blocks from 40 patients with progressive thyroid cancer despite standard-of
      care therapy were screened for PPFP, and the tumor from only one patient (2.5%)
      was positive. The patient had a 6.0-cm acetabular soft tissue metastasis from
      Hurthle cell carcinoma that caused severe pain on weight bearing and had a serum
      thyroglobulin level of 1974 ng/mL. After 24 weeks of therapy with pioglitazone,
      the metastatic lesion was 3.9 cm, the thyroglobulin level was 49.4 ng/mL, and the
      patient was pain-free. Thirteen months after discontinuation of pioglitazone, the
      metastatic lesion was 3.6 cm, the thyroglobulin level was 4.7 ng/mL, and the
      patient remained pain-free. Conclusions: Pioglitazone may be therapeutic in
      patients with PPFP thyroid cancer. However, thyroid cancers that are progressive
      despite standard-of-care therapy appear to only rarely express PPFP.

PMID- 29373713
TI  - Corrigendum: Disruption of OsSEC3A increases the content of salicylic acid and
      induces plant defense responses in rice.

PMID- 29373712
TI  - Whole-Body Single-Cell Sequencing Reveals Transcriptional Domains in the Annelid
      Larval Body.
AB  - Animal bodies comprise diverse arrays of cells. To characterize cellular
      identities across an entire body, we have compared the transcriptomes of single
      cells randomly picked from dissociated whole larvae of the marine annelid
      Platynereis dumerilii. We identify five transcriptionally distinct groups of
      differentiated cells, each expressing a unique set of transcription factors and
      effector genes that implement cellular phenotypes. Spatial mapping of cells into
      a cellular expression atlas, and wholemount in situ hybridization of group
      specific genes reveals spatially coherent transcriptional domains in the larval
      body, comprising, for example, apical sensory-neurosecretory cells versus
      neural/epidermal surface cells. These domains represent new, basic subdivisions
      of the annelid body based entirely on differential gene expression, and are
      composed of multiple, transcriptionally similar cell types. They do not represent
      clonal domains, as revealed by developmental lineage analysis. We propose that
      the transcriptional domains that subdivide the annelid larval body represent
      families of related cell types that have arisen by evolutionary diversification.
      Their possible evolutionary conservation makes them a promising tool for evo-devo
      research.

PMID- 29373714
TI  - Corrigendum: Map-based cloning and characterization of BPH29, a B3 domain
      containing recessive gene conferring brown planthopper resistance in rice.

PMID- 29373716
TI  - Epidemiological trends of cryptococcosis in Italy: Molecular typing and
      susceptibility pattern of Cryptococcus neoformans isolates collected during a 20
      year period.
AB  - In the present study clinical data and isolates from cases of cryptococcosis
      recorded during clinical surveys carried out in Italy from 1997 to 2016, were
      investigated. Molecular typing and antifungal susceptibility testing were
      performed in order to delineate the epidemiological trend of cryptococcosis in
      Italy and to define wild-type population for four different antifungal compounds.
      During the studied period, a total of 302 cases collected from 32 centers of 11
      Italian regions were recorded. Analysis of clinical data showed a significant
      increase of frequency (from 7% to 38%) of cryptococcosis in human
      immunodeficiency virus (HIV)-negative patients primarily with hematologic
      malignancies and solid organ transplantations. The prevalence of the molecular
      types has significantly changed during the study period, showing an increase of
      VNIII isolates from 11% to 41% in HIV-negative patients, and a decrease of VNIV
      isolates from 36% to 16%. Antifungal susceptibility testing allowed us to
      calculate the epidemiological cut-off for flucytosine (1 mg/l), fluconazole (8
      mg/l), itraconazole (0.5 mg/l), and voriconazole (0.25 mg/l). Most of the
      isolates were wild-type strains. Comparison of the MIC distributions according to
      molecular types showed that VNIV isolates had lower MICs for fluconazole and
      itraconazole than the VNI and VIII isolates. The current study emphasizes that
      the epidemiology of cryptococcosis in Italy has significantly changed over the
      last decades.

PMID- 29373715
TI  - Positive-sense RNA viruses reveal the complexity and dynamics of the cellular and
      viral epitranscriptomes during infection.
AB  - More than 140 post-transcriptional modifications (PTMs) are known to decorate
      cellular RNAs, but their incidence, identity and significance in viral RNA are
      still largely unknown. We have developed an agnostic analytical approach to
      comprehensively survey PTMs on viral and cellular RNAs. Specifically, we used
      mass spectrometry to analyze PTMs on total RNA isolated from cells infected with
      Zika virus, Dengue virus, hepatitis C virus (HCV), poliovirus and human
      immunodeficiency virus type 1. All five RNA viruses significantly altered global
      PTM landscapes. Examination of PTM profiles of individual viral genomes isolated
      by affinity capture revealed a plethora of PTMs on viral RNAs, which far exceeds
      the handful of well-characterized modifications. Direct comparison of viral
      epitranscriptomes identified common and virus-specific PTMs. In particular,
      specific dimethylcytosine modifications were only present in total RNA from virus
      infected cells, and in intracellular HCV RNA, and viral RNA from Zika and HCV
      virions. Moreover, dimethylcytosine abundance during viral infection was
      modulated by the cellular DEAD-box RNA helicase DDX6. By opening the Pandora's
      box on viral PTMs, this report presents numerous questions and hypotheses on PTM
      function and strongly supports PTMs as a new tier of regulation by which RNA
      viruses subvert the host and evade cellular surveillance systems.

PMID- 29373717
TI  - Integrated transcriptomic and regulatory network analyses identify microRNA-200c
      as a novel repressor of human pluripotent stem cell-derived cardiomyocyte
      differentiation and maturation.
AB  - Aims: MicroRNAs (miRNAs) are crucial for the post-transcriptional control of
      protein-encoding genes and together with transcription factors (TFs) regulate
      gene expression; however, the regulatory activities of miRNAs during cardiac
      development are only partially understood. In this study, we tested the
      hypothesis that integrative computational approaches could identify miRNAs that
      experimentally could be shown to regulate cardiomyogenesis. Methods and results:
      We integrated expression profiles with bioinformatics analyses of miRNA and TF
      regulatory programs to identify candidate miRNAs involved with cardiac
      development. Expression profiling showed that miR-200c, which is not normally
      detected in adult heart, is progressively down-regulated both during cardiac
      development and in vitro differentiation of human embryonic stem cells (hESCs) to
      cardiomyocytes (CMs). We employed computational methodologies to predict target
      genes of both miR-200c and five key cardiac TFs to identify co-regulated gene
      networks. The inferred cardiac networks revealed that the cooperative action of
      miR-200c with these five key TFs, including three (GATA4, SRF and TBX5) targeted
      by miR-200c, should modulate key processes and pathways necessary for CM
      development and function. Experimentally, over-expression (OE) of miR-200c in
      hESC-CMs reduced the mRNA levels of GATA4, SRF and TBX5. Cardiac expression of
      Ca2+, K+ and Na+ ion channel genes (CACNA1C, KCNJ2 and SCN5A) were also
      significantly altered by knockdown or OE of miR-200c. Luciferase reporter assays
      validated miR-200c binding sites on the 3' untranslated region of CACNA1C. In
      hESC-CMs, elevated miR-200c increased beating frequency, and repressed both Ca2+
      influx, mediated by the L-type Ca2+ channel and Ca2+ transients. Conclusions: Our
      analyses demonstrate that miR-200c represses hESC-CM differentiation and
      maturation. The integrative computation and experimental approaches described
      here, when applied more broadly, will enhance our understanding of the interplays
      between miRNAs and TFs in controlling cardiac development and disease processes.

PMID- 29373719
TI  - Quantification of 15 Psychotropic Drugs in Serum and Postmortem Blood Samples
      after a Modified Mini-QuEChERS by UHPLC-MS-MS.
AB  - The aim of the study was to develop a LC-MS-MS method able to detect and quantify
      a number of frequently prescribed antipsychotic and antidepressant drugs for
      toxicological purposes. Separation of compounds was performed on a C-18 RP column
      by Ultra High-Pressure Chromatography over a 11 min run. A modified single step
      QuEChERS protocol consisted essentially by the addition of acetonitrile,
      potassium carbonate and magnesium sulfate in 100 MUL of sample, vortexing,
      centrifugation and evaporation has been selected. The method achieves
      satisfactory recoveries for 15 psychotropic drugs with a mean R% of 85% and
      provides efficient purification of the sample from endogenous interferences,
      simplicity and short sample handling times. The method was validated and provided
      satisfactory accuracy with recoveries ranging from 85 to 113% and precision with
      CV ranging from 1.2 to 13.2%. LODs were determined to be from 0.0003 to 0.017
      MUg/mL while LOQs were from 0.001 to 0.05 MUg/mL for the 15 drugs. Matrix effect
      was below 20% and the analytes were stable in the matrix for 3 weeks. The method
      proved to be suitable for both analysis of clinical samples for Therapeutic Drug
      Monitoring and antemortem or postmortem whole blood samples of forensic cases. A
      number of samples with clinical and forensic interest were successfully analyzed
      demonstrating the effectiveness of QuEChERS in this field.

PMID- 29373718
TI  - The aberrant splicing of BAF45d links splicing regulation and transcription in
      glioblastoma.
AB  - Background: Glioblastoma, the most aggressive primary brain tumor, is genetically
      heterogeneous. Alternative splicing (AS) plays a key role in numerous
      pathologies, including cancer. The objectives of our study were to determine
      whether aberrant AS could play a role in the malignant phenotype of glioma and to
      understand the mechanism underlying its aberrant regulation. Methods: We obtained
      surgical samples from patients with glioblastoma who underwent 5-aminolevulinic
      fluorescence-guided surgery. Biopsies were taken from the tumor center as well as
      from adjacent normal-appearing tissue. We used a global splicing array to
      identify candidate genes aberrantly spliced in these glioblastoma samples.
      Mechanistic and functional studies were performed to elucidate the role of our
      top candidate splice variant, BAF45d, in glioblastoma. Results: BAF45d is part of
      the switch/sucrose nonfermentable complex and plays a key role in the development
      of the CNS. The BAF45d/6A isoform is present in 85% of over 200 glioma samples
      that have been analyzed and contributes to the malignant glioma phenotype through
      the maintenance of an undifferentiated cellular state. We demonstrate that BAF45d
      splicing is mediated by polypyrimidine tract-binding protein 1 (PTBP1) and that
      BAF45d regulates PTBP1, uncovering a reciprocal interplay between RNA splicing
      regulation and transcription. Conclusions: Our data indicate that AS is a
      mechanism that contributes to the malignant phenotype of glioblastoma.
      Understanding the consequences of this biological process will uncover new
      therapeutic targets for this devastating disease.

PMID- 29373720
TI  - StopWatch: The preliminary evaluation of a smartwatch-based system for passive
      detection of cigarette smoking.
AB  - Introduction: Recent developments in smoking cessation support systems and
      interventions have highlighted the requirement for unobtrusive, passive ways to
      measure smoking behaviour. A number of systems have been developed for this that
      either use bespoke sensing technology, or expensive combinations of wearables and
      smartphones. Here we present StopWatch, a system for passive detection of
      cigarette smoking that runs on a low-cost smartwatch and does not require
      additional sensing or a connected smartphone. Methods: Our system uses motion
      data from the accelerometer and gyroscope in an Android smartwatch to detect the
      signature hand movements of cigarette smoking. It uses machine learning
      techniques to transform raw motion data into motion features, and in turn into
      individual drags and instances of smoking. These processes run on the smartwatch,
      and do not require a smartphone. Results: We conducted preliminary validations of
      the system in daily smokers (n=13) in laboratory and free-living conditions
      running on an Android LG G-Watch. In free-living conditions, over a 24-hour
      period, the system achieved precision of 86% and recall of 71%. Conclusions:
      StopWatch is a system for passive measurement of cigarette smoking that runs
      entirely on a commercially available Android smartwatch. It requires no
      smartphone so the cost is low, and needs no bespoke sensing equipment so
      participant burden is also low. Performance is currently lower than other more
      expensive and complex systems, though adequate for some applications. Future
      developments will focus on enhancing performance, validation on a range of
      smartwatches, and detection of electronic cigarette use. Implications: We present
      a low-cost, smartwatch-based system for passive detection of cigarette smoking.
      It uses data from the motion sensors in the watch to identify the signature hand
      movements of cigarette smoking. The system will provide the detailed measures of
      individual smoking behaviour needed for context-triggered just-in-time smoking
      cessation support systems, and to enable just-in-time adaptive interventions.
      More broadly, the system will enable researchers to obtain detailed measures of
      individual smoking behaviour in free-living conditions that are free from the
      recall errors and reporting biases associated with self-report of smoking.

PMID- 29373722
TI  - Sodium-hydrogen exchange inhibition attenuates glycoside-induced hypertrophy in
      rat ventricular myocytes.

PMID- 29373721
TI  - DARC matter(s) for inflammatory cells.

PMID- 29373723
TI  - CETP inhibition and HDL: what is the trial REVEALing?

PMID- 29373724
TI  - Niels Voigt talks to W. Jonathan Lederer, keynote lecturer at the "Gottingen
      Channels" Symposium 2017.

PMID- 29373725
TI  - Cytosolic Glutamine Synthetase Isozymes Play Redundant Roles in Ammonium
      Assimilation Under Low-Ammonium Conditions in Roots of Arabidopsis thaliana.
AB  - Ammonium is a major nitrogen source for plants; it is assimilated into glutamine
      via a reaction catalyzed by glutamine synthetase (GLN). Arabidopsis expresses
      four cytosolic GLN genes, GLN1; 1, GLN1; 2, GLN1; 3 and GLN1; 4, in roots.
      However, the function and organization of these GLN1 isozymes in ammonium
      assimilation in roots remain unclear. In this study, we aimed to characterize the
      four GLN1 isozymes. The levels of growth of the wild type and gln1 single and
      multiple knockout lines were compared in a hydroponic culture at ammonium
      concentrations of 0.1 and 3 mM. Under the low-ammonium concentration, in single
      mutants for each GLN1 gene, there was little effect on growth, whereas the triple
      mutant for GLN1; 1, GLN1; 2 and GLN1; 3 grew slowly and accumulated ammonium.
      Under the high-ammonium concentration, the single mutant for GLN1; 2 showed 50%
      decreases in fresh weight and glutamine, whereas the other gln1 single mutants
      did not show notable changes in the phenotype. The double mutant for GLN1; 1 and
      GLN1; 2 showed less growth and a lower glutamine concentration than the single
      mutant for GLN1; 2. Promoter analysis indicated an overlapping expression of
      GLN1; 1 with GLN1; 2 in the surface layers of the roots. We thus concluded that:
      (i) at a low concentration, ammonium was assimilated by GLN1; 1, GLN1; 2 and
      GLN1; 3, and they were redundant; (ii) low-affinity GLN1; 2 could contribute to
      ammonium assimilation at concentrations ranging from 0.1 to 3 mM; and (iii) GLN1;
      1 supported GLN1; 2 within the outer cell layers of the root.

PMID- 29373728
TI  - Pathways to Linguistic Isolation Among Older U.S. Immigrants: Assessing the Role
      of Living Arrangements and English Proficiency.
AB  - Objectives: To identify diverse pathways to linguistic isolation (LI) and explain
      the differences in LI for older immigrants from different countries. Method: A
      demographic decomposition of LI was applied to 18 largest origin subgroups of
      foreign-born, ages 65 and older, in the 2010-2014 American Community Survey data.
      Results: LI varied from 12% for older Indians to 68% for older Ukrainians.
      Decomposition analysis identified 3 components: (a) Limited English proficiency
      (LEP); (b) Solitary living; and (c) Limited English of co-resident others. The
      relative contribution of components differed by country of origin, pointing to
      different pathways to LI. Older Mexicans have the highest LEP, but moderate LI
      due to infrequent solitary living and the English proficiency of co-resident
      others. Many Chinese and Vietnamese older adults are LI because they live with
      other LEP adults. Older Europeans' common pathway to LI is solitary living.
      Discussion: Components of LI in ethnic communities can inform communication
      strategies for older LEP lacking access to critical information.

PMID- 29373727
TI  - Determinants of Reduced Genetic Capacity for Butyrate Synthesis by the Gut
      Microbiome in Crohn's Disease and Ulcerative Colitis.
AB  - Background and Aims: Alterations in short chain fatty acid metabolism,
      particularly butyrate, have been reported in inflammatory bowel disease, but
      results have been conflicting because of small study numbers and failure to
      distinguish disease type, activity or other variables such as diet. We performed
      a comparative assessment of the capacity of the microbiota for butyrate
      synthesis, by quantifying butyryl-CoA:acetate CoA-transferase [BCoAT] gene
      content in stool from patients with Crohn's disease [CD; n = 71], ulcerative
      colitis [UC; n = 58] and controls [n = 75], and determined whether it was related
      to active vs inactive inflammation, microbial diversity, and composition and/or
      dietary habits. Methods: BCoAT gene content was quantified by quantitative
      polymerase chain reaction [qPCR]. Disease activity was assessed clinically and
      faecal calprotectin concentration measured. Microbial composition was determined
      by sequencing 16S rRNA gene. Dietary data were collected using an established
      food frequency questionnaire. Results: Reduced butyrate-synthetic capacity was
      found in patients with active and inactive CD [p < 0.001 and p < 0.01,
      respectively], but only in active UC [p < 0.05]. In CD, low BCoAT gene content
      was associated with ileal location, stenotic behaviour, increased inflammation,
      lower microbial diversity, greater microbiota compositional change, and decreased
      butyrogenic taxa. Reduced BCoAT gene content in patients with CD was linked with
      a different regimen characterised by lower dietary fibre. Conclusions: Reduced
      butyrate-synthetic capacity of the microbiota is more evident in CD than UC and
      may relate to reduced fibre intake. The results suggest that simple replacement
      of butyrate per se may be therapeutically inadequate, whereas manipulation of
      microbial synthesis, perhaps by dietary means, may be more appropriate.

PMID- 29373726
TI  - Fibre intake and the development of inflammatory bowel disease: A European
      prospective multi-centre cohort study (EPIC-IBD).
AB  - Background and Aims: Population-based prospective cohort studies investigating
      fibre intake and development of inflammatory bowel disease are lacking. Our aim
      was to investigate the association between fibre intake and the development of
      Crohn's disease [CD] and ulcerative colitis [UC] in a large European population.
      Methods: In total, 401326 participants, aged 20-80 years, were recruited in eight
      countries in Europe between 1991 and 1998. At baseline, fibre intake [total
      fibres, fibres from fruit, vegetables and cereals] was recorded using food
      frequency questionnaires. The cohort was monitored for the development of
      inflammatory bowel disease. Each case was matched with four controls and odds
      ratios [ORs] for the exposures were calculated using conditional logistic
      regression. Sensitivity analyses according to smoking status were computed.
      Results: In total, 104 and 221 participants developed incident CD and UC,
      respectively. For both CD and UC, there were no statistically significant
      associations with either quartiles, or trends across quartiles, for total fibre
      or any of the individual sources. The associations were not affected by adjusting
      for smoking and energy intake. Stratification according to smoking status showed
      null findings apart from an inverse association with cereal fibre and CD in non
      smokers [Quartile 4 vs 1 OR = 0.12, 95% confidence interval = 0.02-0.75, p =
      0.023, OR trend across quartiles = 0.50, 95% confidence interval = 0.29-0.86, p =
      0.017]. Conclusion: The results do not support the hypothesis that dietary fibre
      is involved in the aetiology of UC, although future work should investigate
      whether there may be a protective effect of specific types of fibre according to
      smoking status in CD.

PMID- 29373729
TI  - Resting-state functional connectivity predicts neuroticism and extraversion in
      novel individuals.
AB  - The personality dimensions of neuroticism and extraversion are strongly
      associated with emotional experience and affective disorders. Previous studies
      reported functional magnetic resonance imaging (fMRI) activity correlates of
      these traits, but no study has used brain-based measures to predict them. Here,
      using a fully cross-validated approach, we predict novel individuals' neuroticism
      and extraversion from functional connectivity (FC) data observed as they simply
      rested during fMRI scanning. We applied a data-driven technique, connectome-based
      predictive modeling (CPM), to resting-state FC data and neuroticism and
      extraversion scores (self-reported NEO Five Factor Inventory) from 114
      participants of the Nathan Kline Institute Rockland sample. After dividing the
      whole brain into 268 nodes using a predefined functional atlas, we defined each
      individual's FC matrix as the set of correlations between the activity
      timecourses of every pair of nodes. CPM identified networks consisting of
      functional connections correlated with neuroticism and extraversion scores, and
      used strength in these networks to predict a left-out individual's scores. CPM
      predicted neuroticism and extraversion in novel individuals, demonstrating that
      patterns in resting-state FC reveal trait-level measures of personality. CPM also
      revealed predictive networks that exhibit some anatomical patterns consistent
      with past studies and potential new brain areas of interest in personality.

PMID- 29373731
TI  - The Power of Prevention and Youth Voice: A Strategy for Social Work to Ensure
      Youths' Healthy Development.
AB  - The opening plenary session at the 2017 Annual Conference of the Society for
      Social Work and Research, which focused on ensuring healthy youth development,
      highlighted the need to include young people as partners in research and
      evaluation. In doing so, the conference participants joined the voices of a
      growing group of social work scholars committed to youth participation and
      engagement, who have also highlighted the importance of youth voice in the
      development of prevention strategies and programming that are aligned with the
      lived experience of young people. Presenting four unique social work efforts
      designed to harness the power of youth voice, this article shines a spotlight on
      the role of social work research and practice in harnessing the power of youth
      participation in efforts of promote healthy youth development. This article
      concludes by illustrating the benefits of youth engagement for young people,
      communities, and researchers.

PMID- 29373730
TI  - Cell-cycle regulation of non-enzymatic functions of the Drosophila
      methyltransferase PR-Set7.
AB  - Tight cell-cycle regulation of the histone H4-K20 methyltransferase PR-Set7 is
      essential for the maintenance of genome integrity. In mammals, this mainly
      involves the interaction of PR-Set7 with the replication factor PCNA, which
      triggers the degradation of the enzyme by the CRL4CDT2 E3 ubiquitin ligase. PR
      Set7 is also targeted by the SCFbeta-TRCP ligase, but the role of this additional
      regulatory pathway remains unclear. Here, we show that Drosophila PR-Set7
      undergoes a cell-cycle proteolytic regulation, independently of its interaction
      with PCNA. Instead, Slimb, the ortholog of beta-TRCP, is specifically required
      for the degradation of the nuclear pool of PR-Set7 prior to S phase.
      Consequently, inactivation of Slimb leads to nuclear accumulation of PR-Set7,
      which triggers aberrant chromatin compaction and G1/S arrest. Strikingly, these
      phenotypes result from non-enzymatic PR-Set7 functions that prevent proper
      histone H4 acetylation independently of H4K20 methylation. Altogether, these
      results identify the Slimb-mediated PR-Set7 proteolysis as a new critical
      regulatory mechanism required for proper interphase chromatin organization at
      G1/S transition.

PMID- 29373732
TI  - Study of Novel Autoantibodies in Schizophrenia.
AB  - A recent genome-wide association (GWA) study confirmed 108 genetic loci that were
      strongly associated with schizophrenia. Fifteen schizophrenia-associated genes
      were selected for this study based on a number of selection criteria including
      their high expression in both brain tissues and B-lymphocyte cells. We aimed to
      investigate whether individuals with schizophrenia showed different levels of
      plasma IgG antibodies against protein-derived fragments encoded by these 15
      genes. A total of 356 plasma samples were used to analyze circulating IgG
      antibodies against 18 target peptide antigens using an in-house enzyme-linked
      immunosorbent assay. Of 18 antigens tested, 6 (derived from DPYD, MAD1L1,
      ZNF804A, DRD2, TRANK1, and MMP16, respectively) showed increased IgG levels and 3
      (derived from TSNARE1, TCF4, and VRK2, respectively) showed decreased IgG levels
      in patients with schizophrenia compared with control subjects. Receiver operating
      characteristic (ROC) curve analysis revealed that the anti-TRANK1 IgG assay had
      the area under the ROC curve of 0.68 (95% CI = 0.62-0.73), with the highest
      sensitivity of 20.7% against specificity of 95.2% among all 18 tests. There was
      no difference in positivity of anti-double strand DNA IgG between the patient
      group and the control group and no correlation between total IgG levels and each
      individual IgG level tested. Although risperidone treatment showed confounding
      effects on overall IgG levels in the circulation (combined P = .005), anti-TRANK1
      IgG levels did not appear to be significantly affected (t = 1.358, P = .176). In
      conclusion, this study suggests that circulating anti-TRANK1 IgG is likely to
      serve as a biomarker for identification of a subgroup of schizophrenia.

PMID- 29373733
TI  - Functional relevance of radiographic spinal progression in axial
      spondyloarthritis: results from the GErman SPondyloarthritis Inception Cohort.
AB  - Objectives: The aim of the study was to investigate the functional relevance of
      the development of structural damage in the spine in patients with early axial
      spondyloarthritis (axSpA). Methods: Altogether, 210 patients with early axSpA
      (symptom duration ?10 years) who completed a 2-year clinical and radiographic
      follow-up in the GErman SPondyloarthritis Inception Cohort were included. An
      association between structural damage in the spine [modified Stoke AS Spine Score
      (mSASSS)] and functional status (the BASFI) or spinal mobility (the BASMI) was
      assessed in a longitudinal linear mixed model analysis; both unstandardized
      (beta) and standardized (betastand) regression coefficients were calculated.
      Results: There was an association between mSASSS and BASFI: beta = 0.05 (95% CI:
      0.03, 0.08) and betastand = 0.20 (95% CI: 0.11, 0.59) adjusted for disease
      activity parameters (the BASDAI and CRP), the presence of definite radiographic
      sacroiliitis and sex. An association between mSASSS and BASMI was stronger: beta
      = 0.08 (95% CI: 0.05, 0.11) and betastand = 0.41 (95% CI: 0.25, 0.57) adjusted
      for the same parameters. These data indicate that, over time, an increase of 20
      or 12 mSASSS points would be responsible for an increase of one BASFI or one
      BASMI point, respectively. Disease activity (BASDAI) also showed a significant
      association with BASFI [beta = 0.79 (95% CI: 0.71, 0.86) and betastand = 0.71
      (95% CI: 0.63, 0.77)] and BASMI [beta = 0.22 (95% CI: 0.15, 0.30) and betastand =
      0.28 (95% CI: 0.18, 0.37)]. Conclusion: Structural damage in the spine and
      disease activity are both determinants of the functional status and spinal
      mobility in early axSpA.

PMID- 29373734
TI  - Long-Term Testosterone Administration on Insulin Sensitivity in Older Men With
      Low or Low-Normal Testosterone Levels.
AB  - Background: Serum testosterone levels and insulin sensitivity both decrease with
      age. Severe testosterone deficiency is associated with the development of insulin
      resistance. However, the effects of long-term testosterone administration on
      insulin sensitivity in older men with low or low-normal testosterone levels
      remain unknown. Methods: The Testosterone Effects on Atherosclerosis in Aging Men
      Trial was a placebo-controlled, randomized, double-blind trial. The participants
      were 308 community-dwelling men, >=60 years old, with total testosterone 100 to
      400 ng/dL or free testosterone <50 pg/mL. A subset of 134 nondiabetic men (mean
      age, 66.7 +/- 5.1 years) underwent an octreotide insulin suppression test at
      baseline and at 3 and 36 months after randomization to measure insulin
      sensitivity. Insulin sensitivity was estimated as the steady-state plasma glucose
      (SSPG) concentration at equilibrium during octreotide and insulin administration.
      Secondary outcomes included total lean mass (TLM) and total fat mass (TFM) by
      dual energy x-ray absorptiometry. Results: There was a significant (P = 0.003)
      increase in SSPG in the placebo group, whereas no change was seen in testosterone
      treated subjects from baseline to 36 months; however, the between-group
      differences in change in SSPG over 3 years were not statistically significant
      (+15.3 +/- 6.9 mg/dL in the placebo group vs +6.2 +/- 6.4 mg/dL in the
      testosterone group; mixed-model effect, P = 0.17). Changes in SSPG with
      testosterone treatment were not associated with changes in serum total or free
      testosterone concentrations. Changes in TFM but not TLM were associated with
      increases in SSPG. Stratification by age or baseline total testosterone level did
      not show significant intervention effects. Conclusion: Testosterone
      administration for 36 months in older men with low or low-normal testosterone
      levels did not improve insulin sensitivity.

PMID- 29373735
TI  - Systematic editing of synthetic RIG-I ligands to produce effective antiviral and
      anti-tumor RNA immunotherapies.
AB  - Retinoic acid-inducible gene I (RIG-I) recognizes double-stranded viral RNAs
      (dsRNAs) containing two or three 5' phosphates. A few reports of 5'-PPP
      independent RIG-I agonists have emerged, but little is known about the molecular
      principles underlying their recognition. We recently found that the bent duplex
      RNA from the influenza A panhandle promoter activates RIG-I even in the absence
      of a 5'-triphosphate moiety. Here, we report that non-canonical synthetic RNA
      oligonucleotides containing G-U wobble base pairs that form a bent helix can
      exert RIG-I-mediated antiviral and anti-tumor effects in a sequence- and site
      dependent manner. We present synthetic RNAs that have been systematically
      modified to enhance their efficacy and we outline the basic principles for
      engineering RIG-I agonists applicable to immunotherapy.

PMID- 29373737
TI  - Interleukin 1alpha (IL-1alpha) Promotes Pathogenic Immature Myeloid Cells and IL
      1beta Favors Protective Mature Myeloid Cells During Acute Lung Infection.
AB  - Bacterial pneumonia is a common risk factor for acute lung injury and sepsis
      mediated death, but the mechanisms underlying the overt inflammation and
      accompanying pathology are unclear. Infiltration of immature myeloid cells and
      necrotizing inflammation mediate severe pathology and death during pulmonary
      infection with Francisella tularensis. However, eliciting mature myeloid cells
      provides protection. Yet, the host factors responsible for this pathologic
      immature myeloid cell response are unknown. Here, we report that while the influx
      of both mature and immature myeloid cells is strictly MyD88 dependent, the
      interleukin 1 (IL-1) receptor mediates an important dual function via its ligands
      IL-1alpha and IL-1beta. Although IL-1beta favors the appearance of bacteria
      clearing mature myeloid cells, IL-1alpha contributes to lung infiltration by
      ineffective and pathologic immature myeloid cells. Finally, IL-1alpha and IL
      1beta are not the sole factors involved, but myeloid cell responses during acute
      pneumonia were largely unaffected by lung levels of interleukin 10, interleukin
      17, CXCL1, granulocyte colony-stimulating factor, and granulocyte-macrophage
      colony-stimulating factor.

PMID- 29373736
TI  - Metabolomics of osteoarthritis: emerging novel markers and their potential
      clinical utility.
AB  - OA is a multifactorial and progressive disease with no cure yet. Substantial
      efforts have been made and several biochemical and genetic markers have been
      reported, but neither alone nor in combination is adequate to identify early OA
      changes or determine disease progression with sufficient predictive values.
      Recent advances in metabolomics and its application to the study of OA have led
      to elucidation of involvement of several metabolic pathways and new specific
      metabolic markers for OA. Some of these metabolic pathways affect amino acid
      metabolism, including branched chain amino acids and arginine, and phospholipid
      metabolism involving conversion of phosphatidylcholine to
      lysophosphatidylcholine. These metabolic markers appear to be clinically
      actionable and may potentially improve the clinical management of OA patients. In
      this article, we review the recent studies of metabolomics of OA, discuss those
      novel metabolic markers and their potential clinical utility, and indicate future
      research directions in the field.

PMID- 29373738
TI  - The Relation Between Multiple Informal Caregiving Roles and Subjective Physical
      and Mental Health Status Among Older Adults: Do Racial/Ethnic Differences Exist?
AB  - Purpose of the Study: The present study examined whether race/ethnicity moderated
      the relation between type of caregiving role (none, one, or multiple care
      recipients) and subjective physical and mental health among older adults. Design
      and Methods: The sample was drawn from the 2009 California Health Interview
      Survey. Racially/ethnically diverse adults aged 55 and older (n = 24,241) were
      categorized into 3 groups by caregiving roles: noncaregivers (n = 18,626;
      referent), caregivers with a single caregiving role (n = 4,023), and caregivers
      with multiple caregiving roles (n = 1,772). A 2-way analysis of covariance was
      conducted to test main and interaction effects. Results: After adjustment for
      covariates, noncaregivers reported significantly worse self-rated health and
      lower psychological distress than caregivers with any type of role. The
      interaction between race/ethnicity and caregiving roles was significant only for
      self-rated health (p < .05). Blacks with multiple caregiving roles had poorer
      self-rated health than those with a single caregiving role and better self-rated
      health than noncaregivers, whereas other racial/ethnic groups with multiple
      caregiving roles had better self-rated health compared to both noncaregivers and
      those with a single caregiving role. Our sensitivity analysis showed that
      controlling caregiving-related variables present only among caregivers eliminated
      the differences in self-rated health between the two types of caregivers.
      Implications: Findings suggest that caregivers report better self-rated health
      than noncaregivers and that the relation of multiple caregiving roles with self
      rated health differs by race/ethnicity, with blacks differing from other
      racial/ethnic groups. This implies that caregivers experience gain, or are
      selected into the role of caregiving by virtue of having good health.

PMID- 29373739
TI  - Preclinical Pharmacological Development of Chlorcyclizine Derivatives for the
      Treatment of Hepatitis C Virus Infection.
AB  - Hepatitis C virus (HCV) is a small, single-stranded, positive-sense RNA virus
      that infects more than an estimated 70 million people worldwide. Untreated,
      persistent HCV infection often results in chronic hepatitis, cirrhosis, or liver
      failure, with progression to hepatocellular carcinoma. Current anti-HCV regimens
      comprising direct acting antivirals (DAAs) can provide curative treatment;
      however, due to high costs there remains a need for effective, shorter-duration,
      and affordable treatments. Recently, we disclosed anti-HCV activity of the cheap
      antihistamine chlorcyclizine, targeting viral entry. Following our hit-to-lead
      optimization campaign, we report evaluation of preclinical in vitro absorption,
      distribution, metabolism, and excretion properties, and in vivo pharmacokinetic
      profiles of lead compounds. This led to selection of a new lead compound and
      evaluation of efficacy in chimeric mice engrafted with primary human hepatocytes
      infected with HCV. Further development and incorporation of this compound into
      DAA regimens has the potential to improve treatment efficacy, affordability, and
      accessibility.

PMID- 29373740
TI  - Structural properties and gene-silencing activity of chemically modified DNA-RNA
      hybrids with parallel orientation.
AB  - We report, herein, a new class of RNAi trigger molecules based on the
      unconventional parallel hybridization of two oligonucleotide chains. We have
      prepared and studied several parallel stranded (ps) duplexes, in which the
      parallel orientation is achieved through incorporation of isoguanine and
      isocytosine to form reverse Watson-Crick base pairs in ps-DNA:DNA, ps-DNA:RNA, ps
      (DNA-2'F-ANA):RNA, and ps-DNA:2'F-RNA duplexes. The formation of these duplexes
      was confirmed by UV melting experiments, FRET and CD studies. In addition, NMR
      structural studies were conducted on a ps-DNA:RNA hybrid for the first time.
      Finally, we provide evidence for the unprecedented finding that ps-DNA:RNA and ps
      DNA:2'F-RNA hybrids can engage the RNAi pathway to silence gene expression in
      vitro.

PMID- 29373741
TI  - High rates of cerebral toxoplasmosis in HIV patients presenting with meningitis
      in Accra, Ghana.
AB  - Background: Data on adult meningitis among patients infected with the human
      immunodeficiency virus (HIV) is scarce in western sub-Saharan Africa, including
      Ghana. Methods: HIV-infected adults with a provisional diagnosis of meningitis
      were consecutively enrolled, between August 2014 and January 2016. After patient
      data collection, cerebrospinal fluid (CSF) was obtained and evaluated for
      microbiological aetiologies, cell counts and biochemistry. Caregiver clinicians
      provided limited data for inpatients at the end-point of discharge or death.
      Results: Complete data sets from 84 patients were analysed (inpatients=63,
      outpatients=21). Median age was 40 years with 56% (47/84) being females. Only 30%
      (25/84) of the patients were on antiretroviral therapy (ART). CD4+ T-cell count
      was available for 81% (68/84) of patients and 61.9% (52/84) had counts below 150
      cells/MUL [median and interquartile range=56 (13.8-136)]. Microbiological
      aetiologies were detected in 60.7% (51/84) patients with the following
      distribution-Toxoplasmosis (25%), Epstein-Barr virus (28.6%), Cytomegalovirus and
      Cryptococcus (2.4%) each. Co-infection was identified in 20.7% (17/84) of the
      patients. Conclusion: Patients presenting with symptoms of meningitis had
      advanced HIV/AIDS, a quarter of whom had cerebral toxoplasmosis or infection with
      EBV. A high index of suspicion, laboratory exclusion of cryptococcal meningitis
      and prompt patient management with anti-toxoplasmosis empiric therapy may thus be
      required for optimal treatment.

PMID- 29373742
TI  - Single and joint antibacterial activity of aqueous garlic extract and Manuka
      honey on extended-spectrum beta-lactamase-producing Escherichia coli.
AB  - Background: Multidrug resistance and recent technological advances have renewed
      interest in natural product drug discovery from ancient remedies such as Allium
      sativum (garlic) and honey. This study assessed antibacterial activity of aqueous
      garlic extract (AGE) and Manuka honey on extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli. Methods: Thirty clinical isolates of E. coli were
      collected and screened for ESBL production by double-disc synergy test. Single
      and joint antibacterial activity of AGE and Manuka honey against ESBL-producing
      E. coli were determined by agar well dilution and checkerboard methods,
      respectively. Results: Minimum inhibitory concentration (MIC) and minimum
      bactericidal concentration (MBC) of AGE ranged from 125-250 mg/mL and 250-500
      mg/mL, respectively. MIC and MBC of Manuka honey ranged from 12.5-25% v/v and 25
      50% v/v, respectively. The combination of AGE and Manuka honey exhibited
      different effects on selected ESBL-producing E. coli; synergism (1/4H+1/16G),
      additive (1/8H+1/2G, 1/2H+1/16G), indifference (1/16H+MICG, MICH+1/16G,
      2MICH+1/32G) and antagonism (4MICH+1/32G). Conclusions: Manuka honey exhibited
      greater antibacterial activity against ESBL-producing E. coli than AGE.
      Antibacterial activity, and the interaction of AGE and Manuka honey against ESBL
      producing E. coli are dependent on their concentration. Studies assessing
      antibacterial activity of potent phytochemicals in AGE and honey would provide
      insights to mechanisms of interaction for development of new drug leads.

PMID- 29373744
TI  - Respiratory Syncytial Virus-A ON1 Genotype Emergence in Central Mexico in 2009
      and Evidence of Multiple Duplication Events.
AB  - Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory
      infections. An RSV-A genotype (ON1) that contains a 72-nt duplication was
      reported in 2012 and has since extended worldwide. Methods: We analyzed 345
      respiratory samples obtained between 2003 and 2014 to assess the relevance of ON1
      infections. Nucleotidic and deduced amino acid sequences from viruses detected in
      San Luis Potosi and sequences previously reported were analyzed. Results: RSV ON1
      was detected in 105 samples. The earliest case of ON1 infection was detected in
      November 2009, almost 1 year prior to detection of this virus in Canada. Amino
      acid sequence analysis of the duplication region showed the presence of Y273N and
      L274P substitutions in RSV GA2 viruses that, when combined, resulted in 4
      different GXXSPSQ sequence motifs at positions 272-278. Three of these motifs
      were present in both the original and duplicated regions of ON1 strains.
      Additional signature amino acid substitutions were observed in ON1 strains that
      have the different sequence motifs. Conclusions: ON1 strains include viruses that
      appear to be the result of at least 3 independent duplication events. Molecular
      data of strains from diverse geographical regions should help define the
      frequency and implications of this evolution mechanism.

PMID- 29373743
TI  - A comparison of the electrocortical response to monetary and social reward.
AB  - Affective science research on reward processing has primarily focused on monetary
      rewards. There has been a growing interest in evaluating the neural basis of
      social decision-making and reward processing. The present study employed a within
      subject design and compared the reward positivity (RewP), an event-related
      potential component that is present following favorable feedback and absent or
      reduced following unfavorable feedback, during monetary and social reward tasks.
      Specifically, 114 participants (75 females) completed a monetary reward task and
      a novel social reward task that were matched on trial structure, timing, and
      feedback stimuli in a counterbalanced order. Results indicated that the monetary
      and social RewP were of similar magnitude, positively correlated and demonstrated
      comparable psychometric properties, including reliability and dependability.
      Across both the monetary and social tasks, women demonstrated a greater RewP
      compared with men. This study provides a novel methodological approach toward
      examining the electrocortical response to social reward that is comparable to
      monetary reward.

PMID- 29373745
TI  - Modeling heterotic effects in beef cattle using genome-wide SNP-marker genotypes.
AB  - An objective of commercial beef cattle crossbreeding programs is to
      simultaneously optimize use of additive (breed differences) and non-additive
      (heterosis) effects. A total of 6,794 multibreed and crossbred beef cattle with
      phenotype and Illumina BovineSNP50 genotype data were used to predict genomic
      heterosis for growth and carcass traits by applying two methods assumed to be
      linearly proportional to heterosis. The methods were as follows: 1) retained
      heterozygosity predicted from genomic breed fractions (HET1) and 2) deviation of
      adjusted crossbred phenotype from midparent value (HET2). Comparison of methods
      was based on prediction accuracy from cross-validation. Here, a mutually
      exclusive random sampling of all crossbred animals (n = 5,327) was performed to
      form five groups replicated five times with approximately 1,065 animals per
      group. In each run within a replicate, one group was assigned as a validation
      set, while the remaining four groups were combined to form the reference set. The
      phenotype of the animals in the validation set was assumed to be unknown; thus,
      it resulted in every animal having heterosis values that were predicted without
      using its own phenotype, allowing their adjusted phenotype to be used for
      validation. The same approach was used to test the impact of predicted heterosis
      on accuracy of genomic breeding values (GBV). The results showed positive
      heterotic effects for growth traits but not for carcass traits that reflect the
      importance of heterosis for growth traits in beef cattle. Heterosis predicted by
      HET1 method resulted in less variable estimates that were mostly within the range
      of estimates generated by HET2. Prediction accuracy was greater for HET2 (0.37
      0.98) than HET1 (0.34-0.43). Proper consideration of heterosis in genomic
      evaluation models has debatable effects on accuracy of EBV predictions. However,
      opportunity exists for predicting heterosis, improving accuracy of genomic
      selection, and consequently optimizing crossbreeding programs in beef cattle.

PMID- 29373747
TI  - Effect of nutrition labels on dietary quality among college students: a
      systematic review and meta-analysis.
AB  - Context: College students are at an elevated risk of poor nutrition and eating
      habits. Objective: The aim of this systematic review was to examine and quantify
      the effect of nutrition labels on diet quality in college students. Data Sources:
      Literature searches were conducted in 4 electronic databases. Study Selection:
      Peer-reviewed publications that assessed the effect of nutrition label use on
      food choice or dietary intake in college students were included. Data Extraction:
      Twenty-two randomized controlled trials, cohort studies, and pre-post studies
      were identified. Results: Sixteen studies found label exposure to be associated
      with improved diet. Of the 13 studies reporting calories selected or consumed, 8
      found that posting labels at the point of purchase decreased calories, 4 found no
      effect, and 1 found that calories consumed increased after posting labels. Nine
      of the 12 studies assessing noncaloric measures found that nutrition labels
      positively affected diet quality. Meta-analysis of pre-post studies found a
      decrease of 36 kcal (P < 0.05) with label exposure. Conclusions: Nutrition labels
      had a moderate but positive effect on dietary intake of college students.

PMID- 29373746
TI  - Distinct and redundant functions of three homologs of RNase III in the
      cyanobacterium Synechococcus sp. strain PCC 7002.
AB  - RNase III is a ribonuclease that recognizes and cleaves double-stranded RNA.
      Across bacteria, RNase III is involved in rRNA maturation, CRISPR RNA maturation,
      controlling gene expression, and turnover of messenger RNAs. Many organisms have
      only one RNase III while others have both a full-length RNase III and another
      version that lacks a double-stranded RNA binding domain (mini-III). The genome of
      the cyanobacterium Synechococcus sp. strain PCC 7002 (PCC 7002) encodes three
      homologs of RNase III, two full-length and one mini-III, that are not essential
      even when deleted in combination. To discern if each enzyme had distinct
      responsibilities, we collected and sequenced global RNA samples from the wild
      type strain, the single, double, and triple RNase III mutants. Approximately 20%
      of genes were differentially expressed in various mutants with some operons and
      regulons showing complex changes in expression levels between mutants. Two RNase
      III's had a role in 23S rRNA maturation and the third was involved in copy number
      regulation one of six native plasmids. In vitro, purified RNase III enzymes were
      capable of cleaving some of the known Escherichia coli RNase III target
      sequences, highlighting the remarkably conserved substrate specificity between
      organisms yet complex regulation of gene expression.

PMID- 29373748
TI  - Backscattered electron imaging and elemental analysis of rapidly frozen plant
      cells using variable accelerating voltage.
AB  - Rapidly frozen rosemary leaves were observed at variable accelerating voltages in
      a low-vacuum scanning electron microscope equipped with a cryo transfer system.
      After water was sublimated from the fractured face of the leaf, distinct
      backscattered electron (BSE) images were obtained depending on the accelerating
      voltages applied. At 5 kV, surface cell wall structure was observed, whereas at
      10 and 15 kV chloroplasts lining the inside of the cell wall and membrane were
      visualized. With energy dispersive X-ray microanalysis, elemental information
      corresponding to the BSE images was obtained. Besides visualization of the
      structures and elemental composition close to the living state, information on
      layers at different depths from the surface could be detected by varying the
      accelerating voltage in this system.

PMID- 29373749
TI  - The rear window: structural and functional plasticity in tree responses to
      climate change inferred from growth rings.

PMID- 29373750
TI  - Internal Carotid Artery Bifurcation Aneurysms: Microsurgical Strategies and
      Operative Nuances for Different Aneurysmal Directions.
AB  - BACKGROUND: Internal carotid artery bifurcation aneurysms (ICAbifAs), comprising
      approximately 5% of intracranial aneurysms, are characterized clinically by their
      tendency to occur at a younger age and surgically by the technical difficulties
      posed by their domes being adherent to the frontal lobe, their location at the
      apex of the sylvian fissure, and their relation to myriad perforator complexes.
      OBJECTIVE: To review the nuances of technique and operative strategy specific to
      aneurysmal direction in the light of our experience with ICAbifAs. METHODS:
      ICAbifAs managed at our institute from January 2001 to July 2016 were analyzed.
      Detailed analysis of clinical data, pre- and postoperative radiology, operative
      notes and videos, and clinical outcome was done. RESULTS: Fifty-one patients with
      ICAbifAs were treated in the study period out of which 40 patients underwent
      microsurgical clipping. The median age was 48 yr (range 14-68 yr). Nearly 95% of
      the patients presented in a good clinical grade (World Federation of Neurological
      Surgeons grade 1 and 2). At 6-mo follow-up, 36 patients (90%) had good clinical
      outcome (Glasgow Outcome Scale 4 and 5). According to their direction, ICAbifAs
      were grouped as anteriorly directed (10 cases), superiorly directed (23 cases),
      and posteriorly directed (7 cases). Operative techniques and nuances utilized
      depend on aneurysmal direction and are presented here. CONCLUSION: An appropriate
      surgical strategy based on the direction of ICAbifAs as per the preoperative
      radiology, meticulous dissection of aneurysmal wall from adjacent perforators,
      and clip application with the aim of remodeling the ICA bifurcation are integral
      to achieving a good outcome.

PMID- 29373751
TI  - Inferring putative virulence factors for Pythium insidiosum by proteomic
      approach.
AB  - Pythium insidiosum is the etiologic agent of pythiosis, a life-threatening
      disease that affects human and animals, has difficult diagnosis, and therapy.
      Studies on protein characterization of P. insidiosum are scarce, so we aimed to
      determine the protein profile of P. insidiosum by mass spectrometry and
      bioinformatics strategies targeting in proteins that may act as putative
      virulence factors. Therefore, an extraction protocol was standardized to obtain
      the total proteins of P. insidiosum. By the analysis of Image Master 2D Platinum
      software, it was found that 186 spots ranging between 12 and 89 KDa and
      isoelectric point from 4 to 7. By the analysis of 2D-SDS-PAGE it was possible to
      visualize and excise 103 spots, which were hydrolyzed with trypsin and submitted
      to mass spectrometry, resulting in the identification of 36 different proteins.
      Three of them were classified as proteins supposedly related to virulence factors
      due to its functions, such as glucan 1,3-beta glucosidase, Heat shock protein
      (Hsp) 70 and enolase. These results may contribute to a better understanding of
      the virulence factors of this medically important oomycete, as well as to
      subsidize new studies on diagnosis and therapeutic approaches.

PMID- 29373752
TI  - Identity Disturbance, Feelings of Emptiness, and the Boundaries of the
      Schizophrenia Spectrum.
AB  - Historical and current research on borderline personality disorder reveal certain
      affinities with schizophrenia spectrum psychopathology. This is also the case for
      the borderline criteria of "identity disturbance" and "feelings of emptiness,"
      which reflect symptomatology frequently found in schizophrenia and schizotypal
      personality disorder. Unfortunately, the diagnostic manuals offer limited insight
      into the nature of these criteria, including possible deviations and similarities
      with schizophrenia spectrum symptomatology. In this article, we attempt to
      clarify the concepts of identity disturbance and feelings of emptiness with an
      emphasis on the criteria's differential diagnostic significance. Drawing on
      contemporary philosophy, we distinguish between a "narrative" self and a "core"
      self, suggesting that this distinction may assist differential diagnostic efforts
      and contribute to mark the psychopathological boundaries of these disorders.

PMID- 29373753
TI  - Dicer partner protein tunes the length of miRNAs using base-mismatch in the pre
      miRNA stem.
AB  - Dicer partner proteins Drosophila Loquacious-PB (Loqs-PB) and human TRBP tune the
      length of miRNAs produced by Dicer from a subset of pre-miRNAs and thereby alter
      their target repertoire, by an unknown mechanism. Here, we developed a novel high
      throughput method that we named Dram-seq (Dice randomized pre-miRNA pool and seq)
      to study length distributions of miRNAs produced from thousands of different pre
      miRNA variants. Using Dram-seq, we found that a base-mismatch in the pre-miRNA
      stem can alter the length of miRNAs compared with a base-pair at the same
      position in both Drosophila and human, and is important for the miRNA length
      tuning by Loqs-PB. Loqs-PB directly bound base-mismatched nucleotides in the pre
      miRNA stem. We speculate that Loqs-PB tunes miRNA length by changing the
      conformation of base-mismatched nucleotides in the pre-miRNA stem to that of base
      paired ones and thereby altering the distance of the pre-miRNA stem.

PMID- 29373754
TI  - Age Differences in Face Processing: The Role of Perceptual Degradation and
      Holistic Processing.
AB  - Objectives: We simultaneously investigated the role of three hypotheses regarding
      age-related differences in face processing: perceptual degradation, impaired
      holistic processing, and an interaction between the two. Methods: Young adults
      (YA) aged 20-33-year olds, middle-age adults (MA) aged 50-64-year olds, and older
      adults (OA) aged 65-82-year olds were tested on the context congruency paradigm,
      which allows measurement of face-specific holistic processing across the life
      span (Meinhardt-Injac, Persike & Meinhardt, 2014. Acta Psychologica, 151, 155
      163). Perceptual degradation was examined by measuring performance with faces
      that were not filtered (FSF), with faces filtered to preserve low spatial
      frequencies (LSF), and with faces filtered to preserve high spatial frequencies
      (HSF). Results: We found that reducing perceptual signal strength had a greater
      impact on MA and OA for HSF faces, but not LSF faces. Context congruency effects
      were significant and of comparable magnitude across ages for FSF, LSF, and HSF
      faces. By using watches as control objects, we show that these holistic effects
      reflect face-specific mechanisms in all age groups. Discussion: Our results
      support the perceptual degradation hypothesis for faces containing only HSF and
      suggest that holistic processing is preserved in aging even under conditions of
      reduced signal strength.

PMID- 29373755
TI  - Can We Reduce the Duration of Untreated Psychosis? A Systematic Review and Meta
      Analysis of Controlled Interventional Studies.
AB  - Reduction of duration of untreated psychosis (DUP) is the key strategy of early
      interventions for improving the outcomes of first-episode psychosis. Although
      several controlled interventional studies have been conducted with the aim of
      reducing DUP, the results are highly inconsistent and conflicting. The current
      study systematically searches Web of Science and Ovid for English original
      articles investigating interventions adopted to reduce DUP, compared to a control
      intervention, up to April 6, 2017. Sixteen controlled interventional studies were
      retrieved, including 1964 patients in the intervention arm and 1358 in the
      control arm. The controlled intervention studies were characterized by standalone
      first episode psychosis services, standalone clinical high risk services,
      community interventions, healthcare professional training, and multifocus
      interventions. Random effects meta-analyses were conducted. There was no summary
      evidence that available interventions are successful in reducing DUP during the
      first episode of psychosis (Hedges' g = -0.12, 95% CI = -0.25 to 0.01). Subgroup
      analyses showed no differences within each subgroup, with the exception of
      clinical high risk services (Hedges' g = -0.386, 95% CI = -0.726 to -0.045).
      These negative findings may reflect a parceled research base in the area, lack of
      prospective randomized controlled trials (only 2 randomized cluster designed
      studies were present) and small sample sizes. There was substantial heterogeneity
      (I2 = 66.4%), most of which was accounted by different definitions of DUP onset
      (R2 = .88). Psychometric standardization of DUP definition, improvement of study
      design, and implementation of preventative strategies seem the most promising
      avenues for reducing DUP and improving outcomes of first-episode psychosis.

PMID- 29373756
TI  - Alterations of Intrinsic Connectivity Networks in Antipsychotic-Naive First
      Episode Schizophrenia.
AB  - Background: The investigation of large-scale intrinsic connectivity networks in
      antipsychotic-naive first-episode schizophrenia increases our understanding of
      system-level cerebral dysfunction in schizophrenia while enabling control of
      confounding effects of medication and disease progression. Reports on functional
      connectivity in antipsychotic-naive patients have been mixed and the relation
      between network alterations, psychopathology and cognition is unclear. Methods: A
      total number of 47 patients with first-episode schizophrenia who had never
      received antipsychotic medication and 47 healthy controls were scanned with
      functional magnetic resonance imaging under resting conditions. Main outcome
      measures were differences in functional connectivity between groups and the
      relationship between network alterations, psychopathology and cognition. Results:
      Altered connectivity was found between right central executive network (CEN) and
      right ventral attention network (VAN) (patients > controls, P = .001), left CEN
      and left VAN (P = .002), and between posterior default mode network and auditory
      network (P = .006). Association between network connectivity and clinical
      characteristics was found as interactions between the effects of group and
      sustained attention (P = .005) and between group and processing speed (P = .007)
      on the connectivity between right CEN and right VAN. Conclusions: Our findings
      suggest that the early phase of schizophrenia is characterized by increased
      connectivity between fronto-parietal networks suggested to be involved in the
      control of cognitive and sensory functions. Moreover, the present study suggests
      that the problem of not disengaging the VAN leads to difficulties with attention
      and possibly subjective awareness.

PMID- 29373758
TI  - Drug-Drug Interactions Between PA-824 and Darunavir Based on Pharmacokinetics in
      Rats by LC-MS-MS.
AB  - Currently, patients with co-infection with HIV and tuberculosis are treated with
      more than one drug. PA-824 a new chemical entity and a member of a class of
      compounds known as nitroimidazo-oxazines, has significant antituberculosis
      activity and a unique mechanism of action. Darunavir (PrezistaTM) is a new
      protease inhibitor of HIV-1. A simple, sensitive and rapid LC-MS-MS method has
      been developed and validated for simultaneous determination of PA-824 and
      darunavir. Chromatographic separation was achieved on Agilent Eclipse plus C18
      column (100 mm * 2.1 mm, 3.5 MUm) using gradient elution of acetonitrile-water
      (90:10, v/v) with fast gradient elution at a flow rate of 0.6 mL/min and run time
      of 4.5 min. The mass spectrometer was run in positive electrospray ionization
      mode using multiple reaction monitoring to monitor the mass transitions. The
      method was validated for accuracy, precision, linearity, range, selectivity,
      lower limit of quantification, recovery and matrix effect. All validation
      parameters met the acceptance criteria according to regulatory guidelines. The
      method had been successfully applied to a pharmacokinetic study of fixed dose
      administration of PA-824, darunavir and their combination in rats. The results
      indicated that when co-administration of darunavir could decrease the amount of
      PA-824 in vivo and extend the elimination half-life.

PMID- 29373759
TI  - Results of a Targeted Screening Program for Congenital Cytomegalovirus Infection
      in Infants Who Fail Newborn Hearing Screening.
AB  - Background: Congenital cytomegalovirus (CMV) infection is a major cause of
      sensorineural hearing loss. By law, newborns in Connecticut who fail newborn
      hearing screening are tested for infection with CMV. This targeted screening is
      controversial, because most children with congenital CMV infection are
      asymptomatic, and CMV-related hearing loss can have a delayed onset. Our hospital
      uses a saliva polymerase chain reaction (PCR) assay (confirmed by a urine PCR
      assay) to detect CMV. Here, we report the results of the first year of our
      screening program. Methods: We reviewed the medical records of newborns in the
      Yale New Haven Health System who failed the newborn hearing screening test
      between January 1 and December 31, 2016. Results: Of 10964 newborns, 171 failed
      newborn hearing screening, and 3 of these newborns had positive saliva CMV PCR
      test results. Of these 3 newborns, 2 had positive results on the confirmatory
      test (for 1 of them the confirmatory test was not performed until the infant was
      10 weeks old), and 1 had a negative result on the confirmatory test. Three
      additional newborns with congenital CMV infection were tested because of clinical
      indications (1 for ventriculomegaly on prenatal ultrasound and 2 for CMV
      infection of the mother). Results of audiology follow-up were available for 149
      (87.1%) of the 171 newborns who failed newborn hearing screening; 127 (85.2%) had
      normal results. Conclusion: Our targeted screening program for congenital CMV
      infection had a low yield. Consideration should be given to other strategies for
      identifying children at risk of hearing loss as a result of congenital CMV
      infection.

PMID- 29373760
TI  - Automated annotation of mobile antibiotic resistance in Gram-negative bacteria:
      the Multiple Antibiotic Resistance Annotator (MARA) and database.
AB  - Background: Multiresistance in Gram-negative bacteria is often due to acquisition
      of several different antibiotic resistance genes, each associated with a
      different mobile genetic element, that tend to cluster together in complex
      conglomerations. Accurate, consistent annotation of resistance genes, the
      boundaries and fragments of mobile elements, and signatures of insertion, such as
      DR, facilitates comparative analysis of complex multiresistance regions and
      plasmids to better understand their evolution and how resistance genes spread.
      Objectives: To extend the Repository of Antibiotic resistance Cassettes (RAC) web
      site, which includes a database of 'features', and the Attacca automatic DNA
      annotation system, to encompass additional resistance genes and all types of
      associated mobile elements. Methods: Antibiotic resistance genes and mobile
      elements were added to RAC, from existing registries where possible. Attacca
      grammars were extended to accommodate the expanded database, to allow overlapping
      features to be annotated and to identify and annotate features such as composite
      transposons and DR. Results: The Multiple Antibiotic Resistance Annotator (MARA)
      database includes antibiotic resistance genes and selected mobile elements from
      Gram-negative bacteria, distinguishing important variants. Sequences can be
      submitted to the MARA web site for annotation. A list of positions and
      orientations of annotated features, indicating those that are truncated, DR and
      potential composite transposons is provided for each sequence, as well as a
      diagram showing annotated features approximately to scale. Conclusions: The MARA
      web site (http://mara.spokade.com) provides a comprehensive database for mobile
      antibiotic resistance in Gram-negative bacteria and accurately annotates
      resistance genes and associated mobile elements in submitted sequences to
      facilitate comparative analysis.

PMID- 29373757
TI  - Mutations involving the SRY-related gene SOX8 are associated with a spectrum of
      human reproductive anomalies.
AB  - SOX8 is an HMG-box transcription factor closely related to SRY and SOX9. Deletion
      of the gene encoding Sox8 in mice causes reproductive dysfunction but the role of
      SOX8 in humans is unknown. Here, we show that SOX8 is expressed in the somatic
      cells of the early developing gonad in the human and influences human sex
      determination. We identified two individuals with 46, XY disorders/differences in
      sex development (DSD) and chromosomal rearrangements encompassing the SOX8 locus
      and a third individual with 46, XY DSD and a missense mutation in the HMG-box of
      SOX8. In vitro functional assays indicate that this mutation alters the
      biological activity of the protein. As an emerging body of evidence suggests that
      DSDs and infertility can have common etiologies, we also analysed SOX8 in a
      cohort of infertile men (n = 274) and two independent cohorts of women with
      primary ovarian insufficiency (POI; n = 153 and n = 104). SOX8 mutations were
      found at increased frequency in oligozoospermic men (3.5%; P < 0.05) and POI
      (5.06%; P = 4.5 * 10-5) as compared with fertile/normospermic control populations
      (0.74%). The mutant proteins identified altered SOX8 biological activity as
      compared with the wild-type protein. These data demonstrate that SOX8 plays an
      important role in human reproduction and SOX8 mutations contribute to a spectrum
      of phenotypes including 46, XY DSD, male infertility and 46, XX POI.

PMID- 29373761
TI  - When Gist and Familiarity Collide: Evidence From False Recognition in Younger and
      Older Adults.
AB  - Objectives: Aging is associated with decreased recollection required to offset
      misleading effects of familiarity, as well as an increased mnemonic reliance on
      gist-based over detail-based information. We tested the novel hypothesis that age
      related decrements in overriding familiarity can be eliminated under conditions
      in which gist-based information facilitates retrieval. Method: Twenty-seven
      younger adults and 27 older adults viewed scenes from two categories in an
      incidental encoding phase. In a recognition phase, old scenes were intermixed
      with new scenes from the studied categories and an unstudied category, with each
      new scene reappearing after 4, 18, or 48 intervening scenes. Participants were to
      respond "yes" to old scenes, and "no" to new scenes, including their repetitions.
      Results: Despite encoding the scenes similarly, older adults made more false
      endorsements of new and repeated new scenes from studied categories. Both groups,
      however, were equally unlikely to falsely recognize new and repeated new scenes
      from the unstudied category. Discussion: When helpful gist and misleading
      familiarity collide, gist wins, and eliminates age-related increases in false
      recognition.

PMID- 29373762
TI  - Evolutionary diversification of galactinol synthases in Rosaceae: adaptive roles
      of galactinol and raffinose during apple bud dormancy.
AB  - Galactinol synthase (GolS) is a key enzyme in the biosynthetic pathway of
      raffinose family oligosaccharides (RFOs), which play roles in carbon storage,
      signal transduction, and osmoprotection. The present work assessed the
      evolutionary history of GolS genes across the Rosaceae using several
      bioinformatic tools. Apple (Malus * domestica) GolS genes were transcriptionally
      characterized during bud dormancy, in parallel with galactinol and raffinose
      measurements. Additionally, MdGolS2, a candidate to regulate seasonal galactinol
      and RFO content during apple bud dormancy, was functionally characterized in
      Arabidopsis. Evolutionary analyses revealed that whole genome duplications have
      driven GolS gene evolution and diversification in Rosaceae speciation. The strong
      purifying selection identified in duplicated GolS genes suggests that
      differential gene expression might define gene function better than protein
      structure. Interestingly, MdGolS2 was differentially expressed during bud
      dormancy, concomitantly with the highest galactinol and raffinose levels. One of
      the intrinsic adaptive features of bud dormancy is limited availability of free
      water; therefore, we generated transgenic Arabidopsis plants expressing MdGolS2.
      They showed higher galactinol and raffinose contents and increased tolerance to
      water deficit. Our results suggest that MdGolS2 is the major GolS responsible for
      RFO accumulation during apple dormancy, and these carbohydrates help to protect
      dormant buds against limited water supply.

PMID- 29373764
TI  - [Wernicke-Korsakoff syndrome secondary to cytomegalovirus encephalitis: A case
      report].
AB  - Cytomegalovirus (CMV) is one of the opportunistic microorganisms with the highest
      prevalence in immunocompromised patients. Reactivation has decreased after the
      introduction of highly active antiretroviral therapy (HAART). Encephalitis has
      been reported in the coinfection as one of the most frequent presentations.We
      present the case of a young adult patient with HIV infection and rapid
      neurological deterioration due to classic clinical symptoms and signs of the
      Wernicke-Korsakoff syndrome, with no risk factors for thiamine deficiency, with
      images by nuclear magnetic resonance typical of the syndrome, and identification
      of cytomegalovirus in cerebrospinal fluid. The specific treatment for CMV managed
      to control the symptoms with neurological sequelae in progression towards
      improvement.This is one of the few cases reported in the literature of Wernicke
      syndrome secondary to cytomegalovirus encephalitis.

PMID- 29373765
TI  - [In vitro susceptibility of Cuban Aspergillus spp. strains of clinical and
      environmental origin].
AB  - INTRODUCTION: The behavior of antifungal susceptibility of Aspergillus spp. in
      Cuba remains unknown. The antifungals recommended to treat aspergillosis are
      amphotericin B, itraconazole, voriconazole and echinocandins. The influence of
      the environment may set off the emergence of drug-resistance in these
      microorganisms. OBJECTIVE: To evaluate in vitro susceptibility of Aspergillus
      spp. strains to amphotericin B, itraconazole and voriconazol, and the
      relationship between susceptibility patterns and their origin. MATERIALS AND
      METHODS: Minimum inhibitory concentrations of amphotericin B, itraconazole and
      voriconazole were determined for 60 Aspergillus spp. strains of clinical and
      environmental origin using the M38-A2 method of the Clinical and Laboratory
      Standards Institute. RESULTS: We found 21 amphotericin B resistant strains
      (mainly from clinical samples and hospital environments), as well as three
      itraconazole resistant strains (from non-hospital outdoor and indoor
      environments). No voriconazole resistance was found. No relationship was found
      between strain origin and susceptibility. CONCLUSIONS: Results suggest the
      possible existence of environmental factors or interactions with resistant
      genotypes which may give rise to resistant phenotypes in our country. This is the
      first report of in vitro  Aspergillus spp. resistant strains in Cuba. These
      studies should be broadened and include molecular and phylogenetic analyses.

PMID- 29373763
TI  - Comparative advantages of infrapatellar fat pad: an emerging stem cell source for
      regenerative medicine.
AB  - Growing evidence indicates that infrapatellar fat pad (IPFP)-derived stem cells
      (IPFSCs) exert robust proliferation capacities and multilineage differentiation
      potentials. However, few papers summarize the advantages that the IPFP and IPFSCs
      have in regenerative medicine. In this review we delineate the development and
      anatomy of the IPFP by comparing it with an adjacent fibrous tissue, synovium,
      and a more frequently harvested fat depot, subcutaneous adipose tissue.
      Furthermore, we explore the similarities and differences of stem cells from these
      three tissues in terms of IPFSCs, synovium-derived stem cells and subcutaneous
      adipose tissue-derived stem cells in proliferation capacity and tri-lineage
      differentiation potentials, including chondrogenesis, osteogenesis and
      adipogenesis. Finally, we highlight the advantages of IPFSCs in regenerative
      medicine, such as the abundant accessibility and the ability to resist
      inflammation and senescence, two hurdles for cell-based tissue regeneration.
      Considering the comparative advantages of IPFSCs, the IPFP can serve as an
      excellent stem cell source for regenerative medicine, particularly for cartilage
      regeneration.

PMID- 29373766
TI  - [Optimizing resources to reduce costs to determine HIV viral load in limited
      resources settings].
AB  - INTRODUCTION: HIV viral load testing is a key factor to evaluate the
      accomplishment of the UNAIDS target of 90% of viral suppression among people
      receiving antiretroviral therapy. Pooled samples are a potentially accurate and
      economic approach in resource-constrained settings, but efficiency can be
      negatively affected by high prevalence rates of virological failure. OBJECTIVE:
      Strategies were assessed to increase the relative efficiency of pooled HIV viral
      load testing in resource-constrained settings. MATERIALS AND METHODS: We
      evaluated two strategies: a) plasma samples were not included in pools if
      patients had <12 months on antiretroviral therapy, patients had previous viral
      load >1,000 copies/ml, or were antiretroviral therapy naive patients, and b)
      plasma pools were organized separately for first and second-line antiretroviral
      therapy regimens. Individual viral load tests were used to compare pooled
      results. RESULTS: Negative predictive values were similar for patients on first
      (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens
      (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among
      individuals on first-line antiretroviral therapy was lower than second-line
      antiretroviral therapy patients (p <0.01), resulting in greater savings in
      laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI
      71.0 to 76.7) compared with the group of patients on second-line antiretroviral
      therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). CONCLUSION: Selecting the samples
      to be included in the pools and selecting the pools according to ART regimens are
      criteria that could lead to decreased spending on laboratory tests for HIV viral
      load determination in resource-constrained settings.

PMID- 29373767
TI  - [Characteristics of Clostridium difficile infection in a high complexity hospital
      and report of the circulation of the NAP1/027 hypervirulent strain in Colombia].
AB  - INTRODUCTION: Clostridium difficile is the main pathogen related to healthcare
      associated diarrhea and it is the cause of 20 to 30% of diarrhea cases caused by
      antibiotics. In Colombia and Latin America, the knowledge about the
      epidemiological behavior of this infection is limited. OBJECTIVE: To describe the
      characteristics of a series of patients with C. difficile infection. MATERIALS
      AND METHODS: We performed a descriptive case series study of patients with C.
      difficile infection hospitalized in the Fundacion Clinica Shaio from January,
      2012, to November, 2015. RESULTS: We analyzed 36 patients. The average age was 65
      years. The risk factors associated with the infection were: previous use of
      antibiotics (94.4%), prior hospitalization in the last three months (66.7%) and
      use of proton pump inhibitors (50%). The most common comorbidities were chronic
      kidney disease (41.7%) and diabetes mellitus (30.6%). The most frequent symptoms
      were more than three loose stools per day (97.1%) and abdominal pain (42.9%).
      According to the severity of the disease, 44.4% of cases were classified as mild
      to moderate, 38.9% as severe, and 11.1% as complicated or severe. The detection
      of the toxin by PCR (GeneXpert) was the most common diagnostic procedure (63.8%).
      Global mortality during hospitalization was 8%. We identified four strains with
      serotype NAP1/027 and nine samples positive for binary toxin. CONCLUSION:
      Clostridium difficile infection should be suspected in patients with diarrhea and
      traditional risk factors associated with this disease. We report the circulation
      of the hypervirulent strain serotype NAP1/027 in Colombia, which should be
      countered with epidemiological surveillance and a prompt diagnosis.

PMID- 29373768
TI  - Results of the national surveillance of antimicrobial resistance of
      Enterobacteriaceae and Gram negative bacilli in health care-associated infections
      in Colombia, 2012-2014.
AB  - INTRODUCTION: The Colombian National Antimicrobial Resistance Monitoring System
      for the surveillance of healthcare-associated infections was set up to meet this
      problem in the third quarter of 2012. OBJECTIVE: To describe resistance profiles
      and laboratory-based surveillance based on the information collected by the
      System. MATERIALS AND METHODS: We conducted a retrospective and descriptive study
      of the information notified to the Colombian Public Health Surveillance System
      (Sivigila), and in the Whonet databases covering the period from July 2012 to
      December 2014 provided by the primary data-generating units in the country, as
      well as laboratory surveillance results from 1,642 phenotypic and genotypic tests
      on carbapenemase isolates (927 from Enterobacteriaceae, 614 from Pseudomonas spp.
      and 101 from Acinetobacter spp.). RESULTS: There was a significant increase in
      Escherichia coli resistance to third-generation cephalosporins (reaching 26.3% in
      ICUs and 22.5% in other hospital wards), and Klebsiella pneumoniae resistance to
      ertapenem also increased (reaching 14.6% in ICUs). Acinetobacter baumannii
      carbapenem resistance exceeded 50% in ICUs whereas Pseudomonas aeruginosa had
      lower carbapenem resistance (38.8%). KPC (n = 574) and NDM (n=57) were the most
      frequently occurring carbapenemases in Enterobacteriaceae, VIM (n=229) and KPC
      (n=114) in P. aeruginosa, and OXA-23 in A. baumannii (n=87); several
      carbapenemase combinations were identified, KPC + VIM being the most common in
      Pseudomonas spp. and Enterobacteriaceae. CONCLUSION: The data from the
      surveillance of healthcare-associated infections revealed significant carbapenem
      resistance profiles and antimicrobial resistance mechanisms circulating in
      Colombian healthcare institutions.

PMID- 29373769
TI  - [Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity
      in a sample from Colombian population].
AB  - INTRODUCTION: The genetic makeup of the host contributes to the clinical profile
      of dengue. This could be due to the effect of variants in the genes encoding pro
      inflammatory cytokines. OBJECTIVE: To evaluate the association between the
      variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue
      severity in a sample of Colombian population. MATERIALS AND METHODS: We evaluated
      the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG
      candidate genes, respectively, in 226 patients with dengue infection. The
      genotypes were typed using both polymerase chain reaction (PCR) and restriction
      fragment length polymorphism (RFLP). To determine the risk of different dengue
      phenotypes, we compared allele frequencies with chi-square and genotypes and
      haplotypes using logistic regression. Finally, these analyzes were adjusted with
      data from self-identification or the ancestral genetic component. RESULTS: The A
      allele in the rs2069843 polymorphism, adjusted by self-identification, was
      associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire
      sample, this polymorphism, adjusted by the ancestral genetic component, was
      reproducible. In addition, there were significant associations between GGT and
      GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue
      hemorrhagic fever patients, with and without adjustment by ancestral genetic
      component. Additionally, the AGC allelic combination produced 58.03 pg/ml of
      interleukin-6 more than the GGC combination, regardless of European, Amerindian
      and African genetic components. CONCLUSIONS: The variants of GGT and GAC
      polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG
      genes, respectively, were correlated with the susceptibility to dengue severity
      in a sample of Colombian population.

PMID- 29373770
TI  - [Spirometry in a population of coal miners in Paipa, Colombia].
AB  - INTRODUCTION: Respiratory diseases resulting from exposure to particulate matter
      such as in coal mining remains a research challenge in this country and a public
      health issue. Spirometry is a basic test of fundamental respiratory function for
      the diagnosis and monitoring of these types of chronic lung diseases. OBJECTIVE:
      To determine spirometric values in the coal mining municipality of Paipa and
      their association with age and occupational exposure times. MATERIALS AND
      METHODS: We conducted a descriptive cross-sectional study. The occupational
      respiratory disease questionnaire of the American Thoracic Society (ATS) was
      completed while spirometric measurements were performed and interpreted in
      accordance with international recommendations for conducting the test. RESULTS:
      The sample consisted of 226 coal mining workers of the municipality of Paipa.
      Twenty-eight subjects (12.3%) of the sample showed patterns of obstructive and
      restrictive respiratory disease with mild degrees of severity. Eighty subjects
      (35%) showed a decrease in the forced vital capacity ratio/expiratory volume in
      one second (FVC/FEV1). A statistically significant association between age range
      (p=0.002) and years of mining work (p=0.34) with the development of restrictive
      and obstructive disorders was found. Also, there was a statistically significant
      association between age range (p<0.01) and years of mining work (p<0.01) with
      various degrees of severity of the spirometric pattern. CONCLUSIONS: Spirometry
      is a useful test for detecting the presence of respiratory disorders in the
      population of coal miners. The time of exposure was significantly associated with
      the respiratory disease exhibited by these miners.

PMID- 29373771
TI  - [Estimation of underreporting of Chikungunya virus infection cases in Girardot,
      Colombia, from November, 2014, to May, 2015].
AB  - INTRODUCTION: Chikungunya virus infection in Colombia became epidemic in 2015. It
      is estimated that there is underreporting of cases to the public health
      surveillance system which can induce bias in epidemiological projections for
      decision making, a serious problem, as it veils the real magnitude and actual
      epidemiological importance of this disease. OBJECTIVE: To estimate the
      underreporting of cases of chikungunya infection in the municipality of Girardot,
      Cundinamarca, from November, 2014, to May, 2015. MATERIALS AND METHODS: We
      conducted a descriptive and retrospective study using surveys in 132 blocks
      selected by simple random sampling for community active search and the revision
      of 100% of the individual records of health services and those from the public
      health surveillance system for institutional active search. The data were
      analyzed using EpiInfo, version 7. RESULTS: The attack rate was 64.7%. The
      estimated underreporting was 36.1% for not attending medical consultation while
      24.9% of cases were not reported to the public health surveillance system. The
      principal cause for not seeking medical consultation among those surveyed (n=392;
      43%) was self-medication, followed by the collapse of health services (n=207;
      23%). RESULTS: The attack rate was 64.7%. The estimated underreporting was 36.1%
      for not attending medical consultation while 24.9% of cases were not reported to
      the public health surveillance system. The principal cause for not seeking
      medical consultation among those surveyed (n=392; 43%) was self-medication,
      followed by the collapse of health services (n=207; 23%). CONCLUSION: The overall
      underreporting since the beginning of the epidemic in Girardot was 87.05%.This
      research explains 60.9% of this underreporting.

PMID- 29373772
TI  - [Periodontal microbiota and microorganisms isolated from heart valves in patients
      undergoing valve replacement surgery in a clinic in Cali, Colombia].
AB  - INTRODUCTION: Periodontitis is an infectious disease that affects the support
      tissue of the teeth and it is associated with different systemic diseases,
      including cardiovascular disease. Microbiological studies facilitate the
      detection of microorganisms from subgingival and cardiovascular samples.
      OBJECTIVE: To describe the cultivable periodontal microbiota and the presence of
      microorganisms in heart valves from patients undergoing valve replacement surgery
      in a clinic in Cali. MATERIALS AND METHODS: We analyzed 30 subgingival and
      valvular tissue samples by means of two-phase culture medium, supplemented blood
      agar and trypticase soy agar with antibiotics. Conventional PCR was performed on
      samples of valve tissue. RESULTS: The periodontal pathogens isolated from
      periodontal pockets were: Fusobacterium nucleatum (50%), Prevotella intermedia/
      nigrescens (40%), Campylobacter rectus (40%), Eikenella corrodens (36.7%), Gram
      negative enteric bacilli (36.7%), Porphyromonas gingivalis (33.3%), and
      Eubacterium spp. (33.3%). The pathogens isolated from the aortic valve were
      Propionibacterium acnes (12%), Gram negative enteric bacilli (8%), Bacteroides
      merdae (4%), and Clostridium bifermentans (4%), and from the mitral valve we
      isolated P. acnes and Clostridium beijerinckii. Conventional PCR did not return
      positive results for oral pathogens and bacterial DNA was detected only in two
      samples. CONCLUSIONS: Periodontal microbiota of patients undergoing surgery for
      heart valve replacement consisted of species of Gram-negative bacteria that have
      been associated with infections in extraoral tissues. However, there is no
      evidence of the presence of periodontal pathogens in valve tissue, because even
      though there were valve and subgingival samples positive for Gram-negative
      enteric bacilli, it is not possible to maintain they corresponded to the same
      phylogenetic origin.

PMID- 29373773
TI  - [How to intervene and prevent stunting of children from homes belonging to the
      Sisben in Caldas].
AB  - INTRODUCTION: Growth retardation or chronic malnutrition (low height for age)
      indicates a failure in the natural genetic potential that allows us to growth.
      OBJECTIVE: To estimate predictive models of growth retardation in households with
      children younger than five years in the department of Caldas and registered in
      the identification system of potential beneficiaries of social programs (Sistema
      de Identificacion de Potenciales Beneficiarios de Programas Sociales, Sisben).
      MATERIALS AND METHODS: We conducted an analytical study in all households
      (N=56,987) included in the Sisben III database with the presence of children
      younger than five years (N=33,244). The variables under study were demographic
      and socioeconomic characteristics, health service access, housing, poverty,
      education, job market, and growth retardation. The multivariate analysis was done
      in two phases: first, an exploratory analysis of households using hierarchical
      classification (cluster), then estimation of a nonlinear predictive model
      (probit) with growth retardation as the dependent variable. RESULTS: The largest
      proportion of growth retardation in children younger than five years was found in
      southcentral Caldas, in urban centers, and households with monthly income lower
      than USD$ 65. CONCLUSION: Poverty in Caldas women-headed households with children
      younger than five years registered in the Sisben was the main predictor of growth
      retardation.

PMID- 29373774
TI  - [Mitochondrial DNA diversity in prehispanic bone remains on the eastern Colombian
      Andes].
AB  - INTRODUCTION: DNA extracted from ancient human bones allows to analyze the
      genetic makeup of pre-Columbian populations and to determine the dynamics that
      gave rise to the diversity of contemporary populations. OBJECTIVE: To determine
      the genetic diversity of skeletal remains associated with the Templo del Sol (Sun
      Temple) and their relationship with other contemporary and ancient communities of
      America. MATERIALS AND METHODS: We analyzed 13 individuals belonging to the pre
      Columbian Muisca Period (IX-XVI centuries AD) from the vicinities of the Templo
      del Sol (Sun Temple) (Sogamoso, Boyaca) in the eastern Colombian Andes.
      Mitochondrial DNA was amplified and RFLPs were performed in order to type the
      four traditional Amerindian haplogroups (A, B, C and D). In addition, autosomal
      markers including amelogenin and Y-chromosome STRs were amplified. RESULTS: Among
      the observed mitochondrial lineages, haplogroup A was the most frequent, followed
      by haplogroups B and C; no evidence of haplogroup D was found. The genetic
      variation analysis indicated a similar diversity of pre-ColumbianMuiscas to that
      of contemporary populations belonging to the Chibcha linguistic family from
      Colombia and Central America. Molecular sexing was accomplished and it was
      compared to osteological data. With only one exception, anthropological and
      molecular data were consistent. CONCLUSIONS: Our results contribute new genetic
      elements supporting the hypothesis of Central American origin of the Chibcha
      groups of the Cundiboyacense plateau, and allowed sex typing and kinship
      evaluations.

PMID- 29373775
TI  - [Validation of an analytical methodology to determine polychlorinated biphenyls
      in samples from blood plasma].
AB  - INTRODUCTION: Polychlorinated biphenyls are among the five most toxic persistent
      contaminants for living organisms according to the Agency for Toxic Substances
      and Disease Registry (ATSDR). OBJECTIVE: To standardize and validate an
      analytical method to determine and quantify polychlorinated biphenyl indicators
      in samples from blood plasma by means of gas chromatography-mass spectrometry.
      MATERIALS AND METHODS: We fortified a plasma pool to do the matrix assays.
      Additionally, we used the NIST SRM(r) 1958 reference material for the veracity
      and intermediate accuracy assays. RESULTS: Methodology recovery percentages
      ranged between 88.4 and 97.5%, and the bias was less than 20%. Detection and
      quantification limits were 0.04 MUg/L and 0.10 MUg/L, respectively, for all
      polychlorinated biphenyl indicators. The linearity represented by the
      determination coefficient (R2) varied between 0.9866 and 0.9886. Accuracy,
      expressed as relative standard deviation was less than 20% in all the linear work
      range (0.5-500 MUg/L). Finally, we analyzed 115 samples from Colombian population
      in various zones of the country and we found 65 positive samples, from which two
      samples were above HBM-II (7.0 MUg/L, 2XSigmaPCB 138, 153, 180), and two, above
      HBM-I (3.5 MUg/L, 2XSigmaPCB 138, 153, 180). CONCLUSION: The method we developed
      is accurate for PCB analysis in blood plasma samples and could be used for
      biological surveillance of these contaminants in the Colombian population.

PMID- 29373776
TI  - ?
AB  - Introduccion. El caseinato de sodio, una sal de la caseina utilizada como agente
      proinflamatorio en ratones, es capaz de inducir granulopoyesis en vivo e
      incrementar la produccion de citocinas esenciales en dicho evento.Objetivo.
      Evaluar si el caseinato de sodio es capaz de inducir un efecto biologico en
      celulas de origen linfoide y la produccion de citocinas involucradas con este
      linaje.Materiales y metodos: Se utilizaron ratones hembra BALB/c de 8 a 12
      semanas de edad. Los animales se inyectaron cuatro veces, con intervalos de 48
      horas, por via intraperitoneal con 1 ml de caseinato de sodio (10 % de SFB p/v).
      La poblacion de linfocitos B y la incorporacion de bromodesoxiuridina (BrdU) se
      analizaron mediante citometria de flujo. La deteccion de la interleucina 7 se
      evaluo mediante la tecnica de ELISA.Resultados. Tras la inyeccion por via
      intraperitoneal, el numero de linfocitos B 220+ provenientes del bazo de ratones
      tratados con caseinato de sodio aumento comparados con los que solo recibieron el
      vehiculo como tratamiento (89,01+/-1,03 Vs. 75,66+/-2,08), asi como la
      incorporacion de BrdU en celulas B220+ (38,59+/-4,48 Vs. 11,82+/-1,04). Se
      evidencio, asimismo, el incremento en la concentracion de la interleucina 7 (IL
      7) en el suero de los ratones tratados con caseinato de sodio, comparados con los
      que solo recibieron el vehiculo (62,1+/-17,5 Vs. 26,9+/-4,4 pg/ml).Conclusion. El
      caseinato de sodio fue capaz de aumentar el numero de linfocitos B en bazo de
      ratones, asi como inducir la produccion de IL-7, citocina clave para la
      linfopoyesis B.

PMID- 29373777
TI  - Commented review of the Colombian legislation regarding the ethics of health
      research.
AB  - The scope of ethics in health research transcends its legal framework and the
      regulations established in Resolution 8430 of 1993. These norms represent a
      fundamental tool to determine the minimum protection standards for research
      subjects, and, therefore, they should be known, applied properly, and reflect
      upon by all researchers in the field.Here I present and discuss from an
      analytical point of view the regulations that guide research in health. In this
      framework, health is understood as a multidimensional process, and research in
      health as a multidisciplinary exercise involving basic, clinical and public
      health research, collective health, and other related sciences.The main
      analytical categories are related to the principles and actors involved in
      research (regulatory authorities, ethical committees, and special or vulnerable
      subjects and populations), and to professional ethics codes, in addition to
      informed consents and data management.Despite the contribution of this
      legislation to the qualification of health research, my conclusion is that the
      national legislation in ethics for health research requires updating regarding
      technological and scientific developments, as well as specifications from the
      multiple types of health studies.

PMID- 29373778
TI  - [Urinalysis as a diagnostic tool in severe malaria].
AB  - Malaria accounts for a significant morbidity and mortality rate around the world,
      especially in communities with limited access to healthcare. Some clinical signs
      in urine, like haematuria, coluria and proteinuria, help for the early diagnosis
      of severe malaria cases.A narrative review was conducted by analyzing 91
      publications on studies about severe malaria cases and the use of urinalysis.A
      urinalysis can detect metabolic disturbances and organ injury. Its diagnostic
      utility for frequent complications caused by malaria, such as hepatic injury,
      kidney dysfunction and hemolysis, has been confirmed by recent Colombian
      studies.This test is an easy-to-use tool in outpatient clinics and with
      hospitalized patients to promptly recognize complicated cases, allowing the
      timely identification of different lesions in patients with malaria, thus
      contributing to the reduction of severe morbidity and mortality.

PMID- 29373779
TI  - ?

PMID- 29373780
TI  - Trends in the Management of Spontaneous Pneumothorax: A Single Center Experience.
AB  - Objectives: Management of patients with primary spontaneous pneumothorax is
      controversial.  We sought to review our experience in the treatment of primary
      spontaneous pneumothorax (PSP) by comparing outcomes from video-assisted
      thoracoscopic surgery (VATS) with thoracotomy. : A retrospective review of
      electronic and paper medical charts identified 104 consecutive operations
      performed at University of Kentucky Chandler Medical Center for spontaneous
      pneumothorax management between the dates of January 2000 and January 2013. 
      Follow-up phone calls were made to ensure absence of re-ocurrences outside of our
      hospital system. : Eighty-eight patients (85%) underwent VATS repair with
      unilateral and contralateral recurrence rates of 7% and 11% respectively.  Mean
      operative time was 97 minutes; mean postoperative hospital stay was 6 days. 
      Mechanical pleurodesis/pleurectomy was performed in 94% of cases.  Comparatively
      16 patients (16%) underwent thoracotomy repair with unilateral and contralateral
      recurrence rates of 0.00% and 6% respectively.  Mean operative time for the
      thoracotomy group was 188 minutes; mean postoperative hospital stay was 5 days. 
      Mechanical pleurodesis was performed 12 times (75%). : In our study, the VATS
      group had a significant reduction in operating room time (P = .001), a non
      significant increase in unilateral recurrence (p = .587), and no reduction in
      postoperative length of stay.  Contralateral recurrence rate did not vary between
      groups.

PMID- 29373781
TI  - A Focused Observation Tool Using Dreyfus Stages of Skill Acquisition as an
      Evaluative Scale.
AB  - Focused Observartion (FO) is associated with assessing complex skills and differs
      from generalized observations and evaluations.  We've developed a FO assessing
      clinical procedural skills using Hubert Dreyfus Stages of Skill Acquisition as
      descriptive anchors.  This study sought to analyze the effectiveness of this
      measure of skill progression.  During week 1 and week 4 of training, FO was
      performed repetitively on 6 residents during endotracheal intubation.  Skill
      stage ratings were converted to numerical scores.  A dependent, paired samples t
      test was calculated using total mean score (dependent variable) and an effect
      size.  (Cohen's d) was performed to ascertain the standardized mean difference
      between observations.  A significant improvement in mean scores occurred between
      Week 1 (AVG 1.2, STDV +/- 0.1) and Week 4 (AVG 2.0, STDV +/- 0.1) (t= -3.9,
      p<.05) Calculated Chohen's d indicates that this difference was meaningful.  This
      study demonstrates success in adapting a Focused Observation technique and an
      innovative evaluative scale based upon Dreyfus stages of skill acquisition.

PMID- 29373782
TI  - Traffic Fatalities in West Virginia and the Remaining United States, 2008-2012.
AB  - Purpose: Research has shown that Appalachia has a higher traffic fatality rate
      than the non-Appalachian United States.  This study compared traffic fatality
      rates in West Virginia to the rest of the United States. Methods: Fatality
      Analysis Reporting System and Census data from 2008-2012 were used to calculate
      traffic fatality rates. Poisson regression was used to model rate ratios
      stratified by age, sex, rurality, and transportation type, as well as rate ratios
      per licensed driver, vehicles registered and miles travelled. Results: The West
      Virginia traffic fatality rate was 71% higher that the United States.  Fatality
      rates per-capita were elevated for vehicle passengers and drivers of passenger
      vehicles, and large trucks.  In contrast, rates for pedestrians and bicyclists
      were lower that the rest of the country. Conclusion: Public health intervention
      and further research are likely needed to discern reasons as to why this
      disparity exists in West Virginia.

PMID- 29373783
TI  - Metastatic Renal Cell Carcinoma of the Head and Neck: A Case Series.
AB  - Background: Renal cell carcinoma (RCC) accounts for over 80% of malignant tumors
      arising from the kidney.  However, metastatic RCC to the head and neck is a
      relatively rare entity. Case Presentation: We describe three patients with
      metastatic RCC to the head and neck with the involvement of the parapharyngeal
      space, the level V region of the neck, and the maxillary sinus. Conclusion:
      Metastatic RCC in the head and neck is uncommon; however, it must be taken into
      consideration given a patient with a history of RCC.  Multiple pathways allow for
      the spread of RCC to the head and neck region.  Treatment options include
      mastectomy or local radiation and systemic chemotherapy.

PMID- 29373784
TI  - Delignified and Densified Cellulose Bulk Materials with Excellent Tensile
      Properties for Sustainable Engineering.
AB  - Today's materials research aims at excellent mechanical performance in
      combination with advanced functionality. In this regard, great progress has been
      made in tailoring the materials by assembly processes in bottom-up approaches. In
      the field of wood-derived materials, nanocellulose research has gained increasing
      attention, and materials with advanced properties were developed. However, there
      are still unresolved issues concerning upscaling for large-scale applications.
      Alternatively, the sophisticated hierarchical scaffold of wood can be utilized in
      a top-down approach to upscale functionalization, and one can profit at the same
      time from its renewable nature, CO2 storing capacity, light weight, and good
      mechanical performance. Nevertheless, for bulk wood materials, a wider
      multipurpose industrial use is so far impeded by concerns regarding durability,
      natural heterogeneity as well as limitations in terms of functionalization,
      processing, and shaping. Here, we present a novel cellulose bulk material concept
      based on delignification and densification of wood resulting in a high
      performance material. A delignification process using hydrogen peroxide and
      acetic acid was optimized to delignify the entire bulk wooden blocks and to
      retain the highly beneficial structural directionality of wood. In a subsequent
      step, these cellulosic blocks were densified in a process combining compression
      and lateral shear to gain a very compact cellulosic material with entangled
      fibers while retaining unidirectional fiber orientation. The cellulose bulk
      materials obtained by different densification protocols were structurally,
      chemically, and mechanically characterized revealing superior tensile properties
      compared to native wood. Furthermore, after delignification, the cellulose bulk
      material can be easily formed into different shapes, and the delignification
      facilitates functionalization of the bioscaffold.

PMID- 29373785
TI  - Efficient NIR Emission from Nd, Er, and Tm Complexes with Fluorinated Selenolate
      Ligands.
AB  - (DME)2Ln(SeC6F5)3 (Ln = Nd, Er, Tm) can be isolated in high yield by reductive
      cleavage of the Se-Se bond in (SeC6F5)2 with elemental Ln in DME. All three Ln
      compounds are isostructural, with 8 coordinate Ln bound to four O from DME, three
      terminally bound Se(C6F5), and a dative bond from an arene fluoride to a fluorine
      at the ortho position of one selenolate. Emission measurements indicate that
      these compounds are bright NIR sources.

PMID- 29373786
TI  - Recent Advances in CRISPR Base Editing: From A to RNA.

PMID- 29373788
TI  - Magnetic Structure of SmCo5 from 5 K to the Curie Temperature.
AB  - The crystal and magnetic structure of SmCo5 is determined by neutron powder
      diffraction between 5 K and the Curie temperature. In order to overcome the
      enormous neutron absorption of samarium, a 154Sm isotopically enriched sample was
      used. The ordered magnetic moments of both crystallographically distinct cobalt
      atoms are not significantly different over the whole temperature range. They
      decrease from 2.2 MUB at 5 K to about 0.6 MUB at 1029 K. Samarium's ordered
      magnetic moment decreases from 1.0 MUB at 5 K, runs through a minimum of 0.2 MUB
      around 650 K, and becomes larger than cobalt's ordered magnetic moment above 950
      K. No sign or orientation change of the samarium and cobalt ordered magnetic
      moments is found between the Curie temperature and 5 K. SmCo5 is thus a
      ferromagnet and does not switch to a ferrimagnetic state as discussed in the
      literature.

PMID- 29373787
TI  - Transformations of Nanoenabled Copper Formulations Govern Release, Antifungal
      Effectiveness, and Sustainability throughout the Wood Protection Lifecycle.
AB  - Here we compare the standard European benchmark of wood treatment by molecularly
      dissolved copper amine (Cu-amine), also referred to as aqueous copper amine
      (ACA), against two nanoenabled formulations: copper(II)oxide nanoparticles (CuO
      NPs) in an acrylic paint to concentrate Cu as a barrier on the wood surface, and
      a suspension of micronized basic copper carbonate (CuCO3.Cu(OH)2) for wood
      pressure treatment. After characterizing the properties of the (nano)materials
      and their formulations, we assessed their effects in vitro against three fungal
      species: Coniophora puteana, Gloeophyllum trabeum, and Trametes versicolor,
      finding them to be mediated only partially by ionic transformation. To assess the
      use phase, we quantify both release rate and form. Cu leaching rates for the two
      types of impregnated wood (conventional and nanoenabled) are not significantly
      different at 172 +/- 6 mg/m2, with Cu being released predominantly in ionic form.
      Various simulations of outdoor aging with release sampling by runoff, during
      condensation, by different levels of mechanical shear, all resulted in comparable
      form and rate of release from the nanoenabled or the molecular impregnated woods.
      Because of dissolving transformations, the nanoenabled impregnation does not
      introduce additional concern over and above that associated with the traditional
      impregnation. In contrast, Cu released from wood coated with the CuO acrylate
      contained particles, but the rate was at least 100-fold lower. In the same
      ranking, the effectiveness to protect against the wood-decaying basidiomycete
      Coniophora puteana was significant with both impregnation technologies but
      remained insignificant for untreated wood and wood coated by the acrylic CuO.
      Accordingly, a lifecycle-based sustainability analysis indicates that the CuO
      acrylic coating is less sustainable than the technological alternatives, and
      should not be developed into a commercial product.

PMID- 29373789
TI  - Efficient Transition State Optimization of Periodic Structures through Automated
      Relaxed Potential Energy Surface Scans.
AB  - This work explores how constrained linear combinations of bond lengths can be
      used to optimize transition states in periodic structures. Scanning of
      constrained coordinates is a standard approach for molecular codes with localized
      basis functions, where a full set of internal coordinates is used for
      optimization. Common plane wave-codes for periodic boundary conditions almost
      exlusively rely on Cartesian coordinates. An implementation of constrained linear
      combinations of bond lengths with Cartesian coordinates is described. Along with
      an optimization of the value of the constrained coordinate toward the transition
      states, this allows transition optimization within a single calculation. The
      approach is suitable for transition states that can be well described in terms of
      broken and formed bonds. In particular, the implementation is shown to be
      effective and efficient in the optimization of transition states in zeolite
      catalyzed reactions, which have high relevance in industrial processes.

PMID- 29373790
TI  - Cytotoxic and Noncytotoxic Metabolites from Teratosphaeria sp. FL2137, a Fungus
      Associated with Pinus clausa.
AB  - A new naphthoquinone, teratosphaerone A (1), four new naphthalenones, namely,
      teratosphaerone B (2), structurally related to 1, iso-balticol B (3), iso
      balticol B-4,9-acetonide (4), and (+)-balticol C (5), a new furanonaphthalenone,
      (3a S,9 R,9a S)-1(9a),3(3a),9-hexahydromonosporascone (6), and the known
      metabolite monosporascone (7) were isolated from Teratosphaeria sp. FL2137, a
      fungal strain inhabiting the internal tissue of recently dead but undecomposed
      foliage of Pinus clausa. The structures of 1-6 were elucidated on the basis of
      their spectroscopic data including 2D NMR, and absolute configurations of 2, 3,
      and 6 were determined by the modified Mosher's ester method. When evaluated in a
      panel of five tumor cell lines, metabolites 1 and 7 isolated from a cytotoxic
      fraction of the extract exhibited moderate selectivity for metastatic breast
      adenocarcinoma cell line MDA-MB-231. Of these, 1 showed cytotoxicity to this cell
      line with an IC50 of 1.2 +/- 0.1 MUM.

PMID- 29373791
TI  - Lipovelutibols A-D: Cytotoxic Lipopeptaibols from the Himalayan Cold Habitat
      Fungus Trichoderma velutinum.
AB  - Four novel lipovelutibols A (1), B (2), C (3), and D (4) containing six amino
      acid residues with leucinol at the C-terminus and a fatty acyl moiety (n
      octanoyl) at its N-terminus were isolated from the psychrotrophic fungus
      Trichoderma velutinum collected from the Himalayan cold habitat. The structures
      (1-4) were determined by NMR and MS/MS, and the stereochemistry of amino acids by
      Marfey's method. Lipopeptaibols 2 and 4 were found to contain d-isovaline, a
      nonproteinogenic amino acid, but lacked alpha-aminoisobutyric acid,
      characteristic of peptaibols. Cytotoxic activity of 2 and 4 was observed against
      HL-60, LS180, MDA-MB-231, and A549 cancer cell lines.

PMID- 29373792
TI  - Structure Reassignment of Cryptorigidifoliols E and K.
AB  - The structures of the alpha-pyrones cryptorigidifoliols E (5) and K (11) have
      been reassigned as 5C and 11C.

PMID- 29373794
TI  - Selective Synthesis of (Z)-Diazadiphosphafulvalene from 2,2'-bis-Azaphosphindole.
AB  - The unprecedented 2,2'-bis(azaphosphindole) has been synthesized via a new route.
      Reaction with NaH afforded a dianion derivative 5, which is easily transformed to
      alkylated bis(azaphosphindole) or (Z)-P,P,N,N-cisoid diazadiphosphafulvalene. The
      reaction features good regioselectivity and high steroselectivity. Relatively
      strong fluorescence is observed with diazadiphosphafulvalenes. The X-ray crystal
      structure analysis showed that dianion ligand 5 is bonded to two Na atoms in a
      bridging cis-fashion, which allows the synthesis of diazadiphosphafulvalene in a
      highly stereoselective approach.

PMID- 29373793
TI  - The Thermodynamics of Anion Complexation to Nonpolar Pockets.
AB  - The interactions between nonpolar surfaces and polarizable anions lie in a gray
      area between the hydrophobic and Hofmeister effects. To assess the affinity of
      these interactions, NMR and ITC were used to probe the thermodynamics of eight
      anions binding to four different hosts whose pockets each consist primarily of
      hydrocarbon. Two classes of host were examined: cavitands and cyclodextrins. For
      all hosts, anion affinity was found to follow the Hofmeister series, with
      associations ranging from 1.6-5.7 kcal mol-1. Despite the fact that cavitand
      hosts 1 and 2 possess intrinsic negative electrostatic fields, it was determined
      that these more enveloping hosts generally bound anions more strongly. The
      observation that the four hosts each possess specific anion affinities that
      cannot be readily explained by their structures, points to the importance of
      counter cations and the solvation of the "empty" hosts, free guests, and host
      guest complexes, in defining the affinity.

PMID- 29373796
TI  - Risk Assessment Tools in Pulmonary Arterial Hypertension. Prognosis for
      Prospective Trials?

PMID- 29373795
TI  - Asymmetric Synthesis of Chiral Acyclic Purine Nucleosides Containing a Hemiaminal
      Ester Moiety via Three-Component Dynamic Kinetic Resolution.
AB  - An efficient route to construct chiral acyclic purine nucleosides containing a
      hemiaminal ester moiety is reported via three-component dynamic kinetic
      resolution of purines, aldehydes, and acid anhydrides. The procedure provides
      diverse chiral acyclic purine nucleoside analogues in a regioselective manner
      with good yields (up to 93% yield) and excellent enantioselectivities (up to 95%
      ee). Furthermore, the chiral (acyloxyalkyl)-5-fluorouracil could also be
      generated as a potential prodrug of 5-fluorouracil.

PMID- 29373798
TI  - Is It Time to Consider Obstructive Sleep Apnea Syndrome a Risk Factor for
      Alzheimer's Disease?

PMID- 29373797
TI  - Does Extracorporeal Membrane Oxygenation Improve Survival in Pediatric Acute
      Respiratory Failure?
AB  - RATIONALE: Extracorporeal membrane oxygenation (ECMO) has supported gas exchange
      in children with severe respiratory failure for more than 40 years, without ECMO
      efficacy studies. OBJECTIVES: To compare the mortality and functional status of
      children with severe acute respiratory failure supported with and without ECMO.
      METHODS: This cohort study compared ECMO-supported children to pair-matched non
      ECMO-supported control subjects with severe acute respiratory distress syndrome
      (ARDS). Both individual case matching and propensity score matching were used.
      The study sample was selected from children enrolled in the cluster-randomized
      RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure)
      clinical trial. Detailed demographic and daily physiologic data were used to
      match patients. The primary endpoint was in-hospital mortality. Secondary
      outcomes included hospital-free days, ventilator-free days, and change in
      functional status at hospital discharge. MEASUREMENTS AND MAIN RESULTS: Of 2,449
      children in the RESTORE trial, 879 (35.9%) non-ECMO-supported patients with
      severe ARDS were eligible to match to 61 (2.5%) ECMO-supported children. When
      individual case matching was used (60 matched pairs), the in-hospital mortality
      rate at 90 days was 25% (15 of 60) for both the ECMO-supported and non-ECMO
      supported children (P > 0.99). With propensity score matching (61 matched pairs),
      the ECMO-supported in-hospital mortality rate was 15 of 61 (25%), and the non
      ECMO-supported hospital mortality rate was 18 of 61 (30%) (P = 0.70). There was
      no difference between ECMO-supported and non-ECMO-supported patients in any
      secondary outcomes. CONCLUSIONS: In children with severe ARDS, our results do not
      demonstrate that ECMO-supported children have superior outcomes compared with non
      ECMO-supported children. Definitive answers will require a rigorous multisite
      randomized controlled trial.

PMID- 29373800
TI  - Household Air Pollution and Chronic Obstructive Pulmonary Disease. "A Riddle,
      Wrapped in a Mystery, Inside an Enigma".

PMID- 29373799
TI  - The Role of the Vascular and Structural Response to Activity in the Development
      of Achilles Tendinopathy: A Prospective Study.
AB  - BACKGROUND: Several risk factors have been suggested in the development of
      Achilles tendinopathy, but large-scale prospective studies are limited. PURPOSE:
      To investigate the role of the vascular response to activity of the Achilles
      tendon, tendon thickness, ultrasound tissue characterization (UTC) of tendon
      structure, and foot posture as possible risk factors in the development of
      Achilles tendinopathy. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS:
      The study began with 351 first-year students at Ghent University. After 51
      students were excluded, 300 were tested in the academic years 2013-2014 and 2014
      2015 and were followed prospectively for 2 consecutive years by use of a
      multilevel registration method. Of those, 250 students were included in the
      statistical analysis. At baseline, foot posture index and UTC were investigated
      bilaterally. Blood flow and tendon thickness were measured before and after a
      running activity. Cox regression analyses were performed to identify significant
      contributors to the development of Achilles tendinopathy. RESULTS: During the 2
      year follow-up, 27 of the included 250 participants developed Achilles
      tendinopathy (11%). Significant predictive effects were found for female sex and
      blood flow response after running ( P = .022 and P = .019, respectively). The
      risk of developing Achilles tendinopathy increased if the blood flow increase
      after running was reduced, regardless of sex, foot pronation, and timing of flow
      measurements. The model had a predictive accuracy of 81.5% regarding the
      development of Achilles tendinopathy, with a specificity of 85.0% and a
      sensitivity of 50.0%. CONCLUSION: This prospective study identified both female
      sex and the diminished blood flow response after running as significant risk
      factors for the development of Achilles tendinopathy. UTC of tendon structure,
      Achilles tendon thickness, and foot posture did not significantly contribute to
      the prediction of Achilles tendinopathy. A general evaluation of tendon structure
      by UTC, measurement of tendon thickness, or determination of the foot posture
      index will not allow clinicians to identify patients at risk for developing
      Achilles tendinopathy. Furthermore, it may be possible to improve blood flow
      after activity by using noninvasive techniques (such as prostaglandins,
      compression stockings, heat, massage, and vibration techniques). These techniques
      may be useful in the prevention and management of Achilles tendinopathy, but
      further research is needed.

PMID- 29373801
TI  - Long-term Clinical Outcomes After Microfracture of the Glenohumeral Joint:
      Average 10-Year Follow-up.
AB  - BACKGROUND: Microfracture is an effective surgical treatment for full-thickness
      cartilage defects of the knee; however, little is known regarding long-term
      outcomes after microfracture in the shoulder. PURPOSE: To present long-term
      clinical outcomes of patients undergoing microfracture of full-thickness
      articular cartilage defects of the glenohumeral joint. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: Sixteen consecutive patients (17 shoulders) were
      retrospectively reviewed who underwent arthroscopic microfracture of the humeral
      head and/or glenoid surface, with or without additional procedures between 2001
      and 2008 and with a minimum follow-up of 8.5 years. All patients completed pre-
      and postoperative surveys containing the visual analog scale, American Shoulder
      and Elbow Surgeons form, and Simple Shoulder Test. Complications and reoperations
      were analyzed. Failure was defined by biological resurfacing or conversion to
      arthroplasty. RESULTS: Of the original 16 patients (17 shoulders), 13 patients
      (14 shoulders) were available for mean follow-up at 10.2 +/- 1.8 years after
      microfracture (range, 8.5-15.8 years), for an overall clinical follow-up rate of
      82%. The patients (6 men, 7 women) were 36.1 +/- 12.9 years old at time of
      microfracture. The average size of humeral head defects was 5.20 cm2 (range, 4.0
      7.84 cm2), and the average size of glenoid defects was 1.53 cm2 (range, 1.0-3.75
      cm2). Four patients (4 shoulders) underwent at least 1 reoperation, and 3 were
      considered to have structural failures. The average time to failure was 3.7 years
      after microfracture (range, 0.2-9.6 years). The overall survival rate was 76.6%
      at 9.6 years. For these patients, there were statistically significant
      improvements in visual analog scale, Simple Shoulder Test, and American Shoulder
      and Elbow Surgeons scores as compared with preoperative values at long-term
      follow-up ( P < .05 for all), without any significant change from short-term
      (mean, 2.3 years) to long-term (mean, 10.2 years) follow-up. There was no
      significant difference in Single Assessment Numeric Evaluation or Short Form-12
      Physical or Mental scores between short- and long-term follow-up. When compared
      with short-term follow-up, in which 2 patients had already failed, 1 additional
      patient progressed to failure at 9.6 years after the original microfracture. Two
      patients (2 shoulders) were considered to have clinical failure. Owing to the
      overall number of failures (3 structural failure and 2 clinical failure), the
      total long-term success rate of glenohumeral microfracture is 66.7% in the
      current study. CONCLUSION: Treating full-thickness symptomatic chondral defects
      of the glenohumeral joint with microfracture can result in long-term improved
      function and reduced pain for some patients. However, in this case series, 21.4%
      of patients required conversion to arthroplasty <10 years after the index
      microfracture procedure, and 33% to 42% of patients were considered to have
      potential clinical failure. Additional studies with larger patient cohorts are
      needed.

PMID- 29373803
TI  - Knockdown of Nrf2 inhibits angiogenesis by downregulating VEGF expression through
      PI3K/Akt signaling pathway in cerebral microvascular endothelial cells under
      hypoxic conditions.
AB  - Ischemic stroke is a major cerebrovascular disease resulting from a transient or
      permanent local reduction of cerebral blood flow. Angiogenesis plays an important
      role in cerebral microvascular repair after ischemic stroke. This study aimed at
      investigating the effect of NF-E2-related factor 2 (Nrf2) on the angiogenesis of
      mouse cerebral microvascular endothelial bEnd.3 cells in a hypoxic environment.
      We found that Nrf2 expression was temporarily increased in hypoxia-induced bEnd.3
      cells. Knockdown of Nrf2 inhibited the proliferation, migration, as well as tube
      formation in hypoxia-induced bEnd.3 cells. Meanwhile, vascular endothelial growth
      factor and PI3K/Akt signaling pathways were identified to be regulated by Nrf2 in
      hypoxia-induced bEnd.3 cells. It was found that silencing of Nrf2 downregulated
      the expression levels of NAD(P)H:quinine oxidoreductase-1, vascular endothelial
      growth factor, p-Akt, and heme oxygenase-1 in hypoxia-induced bEnd.3 cells. Data
      suggested that hypoxia induced the transient increase of Nrf2, which plays a key
      role in the angiogenesis of cerebral microangiogenesis, and that Nrf2 regulates
      the proliferation, migration, as well as tube formation likely through PI3K/Akt
      signaling pathway in hypoxia-induced bEnd.3 cells. Our study provides proof of
      concept for the modulation of Nrf2, so as to tilt the balance toward
      angiogenesis, representing a therapeutic strategy for hypoxia or ischemia
      disorders such as stroke.

PMID- 29373802
TI  - Positive End-Expiratory Pressure Lower Than the ARDS Network Protocol Is
      Associated with Higher Pediatric Acute Respiratory Distress Syndrome Mortality.
AB  - RATIONALE: The ARDS Network (ARDSNet) used a positive end-expiratory pressure
      (PEEP)/FiO2 model in many studies. In general, pediatric intensivists use less
      PEEP and higher FiO2 than this model. OBJECTIVES: To evaluate whether children
      managed with PEEP lower than recommended by the ARDSNet PEEP/FiO2 model had
      higher mortality. METHODS: This was a multicenter, retrospective analysis of
      patients with pediatric acute respiratory distress syndrome (PARDS) managed
      without a formal PEEP/FiO2 protocol. Four distinct datasets were combined for
      analysis. We extracted time-matched PEEP/FiO2 values, calculating the difference
      between PEEP level and the ARDSNet-recommended PEEP level for a given FiO2. We
      analyzed the median difference over the first 24 hours of PARDS diagnosis against
      ICU mortality and adjusted for confounding variables, effect modifiers, or
      factors that may have affected the propensity to use lower PEEP. MEASUREMENTS AND
      MAIN RESULTS: Of the 1,134 patients with PARDS, 26.6% were managed with lower
      PEEP relative to the amount of FiO2 recommended by the ARDSNet protocol. Patients
      managed with lower PEEP experienced higher mortality than those who were managed
      with PEEP levels in line with or higher than recommended by the protocol (P <
      0.001). After adjustment for hypoxemia, inotropes, comorbidities, severity of
      illness, ventilator settings, nitric oxide, and dataset, PEEP lower than
      recommended by the protocol remained independently associated with higher
      mortality (odds ratio, 2.05; 95% confidence interval, 1.32-3.17). Findings were
      similar after propensity-based covariate adjustment (odds ratio, 2.00; 95%
      confidence interval, 1.24-3.22). CONCLUSIONS: Patients with PARDS managed with
      lower PEEP relative to FiO2 than recommended by the ARDSNet model had higher
      mortality. Clinical trials targeting PEEP management in PARDS are needed.

PMID- 29373804
TI  - Quantitative trait loci analysis of root traits under phosphorus deficiency at
      the seedling stage in wheat.
AB  - Deficiency of available phosphorus (P) in soil limits wheat production and
      creates a need to develop P-deficiency-tolerant cultivars. Plant roots, important
      organs for absorbing nutrients and synthesizing growth regulators, are good
      candidates for P-efficiency screening. In this study, we evaluated five root
      traits under hydroponic culture conditions either with (AP) or without (NP)
      applied P in a recombinant inbred line population (H461/CM107) of Triticum
      aestivum L. at the seedling stage. Four significant quantitative trait loci (QTL)
      were detected, on chromosomes 1D, 2D, 3D, and 7D in NP-treated plants, explaining
      up to 13.0%, 11.0%, 14.4%, and 12.8% of the phenotypic variance, respectively.
      Among these QTL, Qrt.sicau-3D and Qrt.sicau-7D showed pleiotropic and additive
      effects. All QTL were found to be novel. The diversity array technology markers
      flanking the QTL were converted to simple sequence repeat markers that can be
      deployed in future genetic studies of P deficiency. These QTL lead to an increase
      in root biomass and respond to P-deficiency stress; these characteristics are
      crucial to improve root traits for breeding or further investigation of the
      gene(s) involved in P-deficiency tolerance.

PMID- 29373805
TI  - Systematic Review and Meta-analysis of Outcomes After Hip Arthroscopy in
      Femoroacetabular Impingement.
AB  - BACKGROUND: Femoroacetabular impingement (FAI) has become a more commonly
      recognized cause of limited hip range of motion and hip pain among young adults
      and athletes. Hip arthroscopy is recommended for the surgical treatment of this
      disorder, unless specific contraindications exist. Despite the increasing rate of
      published studies in this area, there remains no aggregate data for outcomes
      after this approach. PURPOSE: To evaluate risk factors and outcomes after
      arthroscopic management of FAI, including return to play, revision rate, surgical
      and nonsurgical complications, change in alpha-angle, intraoperative bone
      resection, and patient-reported outcomes. STUDY DESIGN: Meta-analysis and
      systematic review. METHODS: A review of the current literature was performed with
      the terms "femoroacetabular impingement," "hip arthroscopy," and numerous
      variations thereof in PubMed, EMBASE, BioMed Central, Cochrane, Science Direct,
      and Scopus, yielding 1723 abstracts. After screening by eligibility criteria, 31
      articles were included. The incidence of bilateral FAI was determined by
      enrollment data, and pooled estimates were calculated for postoperative patient
      reported outcome measures, alpha-angles, return to sport, postoperative
      complications, and reoperation risk. RESULTS: A total of 1981 hips among 1911
      patients were identified, with a mean +/- SD age of 29.9 +/- 1.9 years and 29.5
      +/- 14.0 months of follow-up. The incidence of bilateral FAI in these studies
      that required operative intervention was 3.6%. The pooled risk of reoperation
      after hip arthroscopy, including revision surgery or subsequent total hip
      arthroplasty, was 5.5% (95% CI, 3.6%-7.5%). The risk of clinical complications
      was 1.7% (95% CI, 0.9%-2.5%). In total, 87.7% of patients demonstrated return to
      sport after surgery (95% CI, 82.4%-92.9%, P < .001), and all patient-reported
      outcomes improved postoperatively, with the highest increase observed in the Hip
      Outcome Score sports scale (41.7 points; 95% CI, 34.1-49.4; P < .001). The alpha
      angle decreased by an average of 23.6 degrees  (95% CI, 18.2 degrees -29.0
      degrees ; P < .001). We identified 11 factors associated with the success of hip
      arthroscopy in FAI and 16 factors associated with failure or negative outcomes.
      CONCLUSION: A high percentage of patients return to sport activities after hip
      arthroscopy for FAI, with a low rate of complications and reoperation. All
      patient-reported outcome measures, except for mental health, significantly
      improved after surgery.

PMID- 29373806
TI  - Intra-articular Injections of Platelet-Rich Plasma Releasate Reduce Pain and
      Synovial Inflammation in a Mouse Model of Osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease leading to pain
      and disability for which no curative treatment exists. A promising biological
      treatment for OA is intra-articular administration of platelet-rich plasma (PRP).
      PRP injections in OA joints can relieve pain, although the exact working
      mechanism is unclear. PURPOSE: To examine the effects of PRP releasate (PRPr) on
      pain, cartilage damage, and synovial inflammation in a mouse OA model. STUDY
      DESIGN: Controlled laboratory study. METHODS: OA was induced unilaterally in the
      knees of male mice (n = 36) by 2 intra-articular injections of collagenase at
      days -7 and -5. At day 0, pain was measured by registering weight distribution on
      the hindlimbs, after which mice were randomly divided into 2 groups. Mice
      received 3 intra-articular injections of PRP or saline in the affected knee.
      Seven mice per group were euthanized at day 5 for assessment of early synovial
      inflammation and cartilage damage. Pain in the remaining mice was registered for
      a total of 3 weeks. These mice were euthanized at day 21 for assessment of
      cartilage damage and synovial inflammation on histological evaluation. Antibodies
      against iNOS, CD163, and CD206 were used to identify different subtypes of
      macrophages in the synovial membrane. RESULTS: Mice in the PRPr group increased
      the distribution of weight on the affected joint in 2 consecutive weeks after the
      start of the treatment ( P < .05), whereas mice in the saline group did not. At
      day 21, PRPr-injected knees had a thinner synovial membrane ( P < .05) and a
      trend toward less cartilage damage in the lateral joint compartment ( P = .053)
      than saline-injected knees. OA knees treated with saline showed less anti
      inflammatory (CD206+ and CD163+) cells at day 5 than healthy knees, an
      observation that was not made in the PRPr-treated group. A higher level of pain
      at day 7 was associated with a thicker synovial membrane at day 21. The presence
      of CD206+ cells was negatively associated with synovial membrane thickness.
      CONCLUSION: In a murine OA model, multiple PRPr injections reduced pain and
      synovial thickness, possibly through modulation of macrophage subtypes. CLINICAL
      RELEVANCE: PRPr injections in early OA or shortly after joint trauma can reduce
      pain and synovial inflammation and may inhibit OA development in patients.

PMID- 29373807
TI  - Prostate ultrasound imaging: evaluation of a two-step scoring system in the
      diagnosis of prostate cancer.
AB  - RATIONALE AND OBJECTIVES: This study aims to investigate the feasibility and
      performance of a two-step scoring system of ultrasound imaging in the diagnosis
      of prostate cancer. MATERIAL AND METHODS: 75 patients with 888 consecutive
      histopathologically verified lesions were included in this study. Step 1, an
      initial 5-point scoring system was developed based on conventional transrectal
      ultrasound (TRUS). Step 2, a final scoring system was evaluated according to
      contrast-enhanced transrectal ultrasound (CE-TRUS). Each lesion was evaluated
      using the two-step scoring system (step 1 + step 2) and compared with only using
      conventional TRUS (step 1). RESULTS: 888 lesions were histologically verified:
      315 of them were prostate cancer from 46 patients and 573 were benign prostatic
      hypertrophy (BPH) from 29 patients. According to the two-step scoring system, 284
      lesions were upgraded and 130 lesions were downgraded from step 1 to step 2 (this
      means using step 2 to assess the results by step 1). However, 96 cases were
      improperly upgraded after step 2 and 48 malignant lesions were still missed after
      step 2 as score-1. For the two-step scoring system, the sensitivity, specificity,
      and accuracy were 84.7%, 83.2%, and 83.7%, respectively, versus 22.8%, 96.6%, and
      70.4%, respectively, for conventional TRUS. The area under the ROC curve (AUC)
      for lesion diagnosis was 0.799-0.952 for the two-step scoring system, versus
      0.479-0.712 for conventional TRUS. The difference in the diagnostic accuracy of
      the two-step scoring system and conventional TRUS was statistically significant
      (P<0.0001). CONCLUSION: The two-step scoring system was straightforward to use
      and achieved a considerably accurate diagnostic performance for prostate cancer.
      The application of the two-step scoring system for prostate cancer is promising.

PMID- 29373808
TI  - Post-vitrectomy cataract acceleration in phakic eyes: a review.
AB  - Vitrectomy is considered the standard therapy for the treatment of posterior
      segment disease; however, after a significant improvement of the visual acuity,
      there is a reduction in visual acuity due to cataract formation, which requires
      further surgery. Nuclear sclerotic cataract (NSC) is the most common type of
      cataract seen after vitrectomy. The pathogenesis of post-vitrectomy NSC is
      unclear; several hypotheses have been formulated without any conclusions. In
      order to correct post-vitrectomy NSC, phacoemulsification with intraocular lens
      implantation is performed. This surgery itself has some complications, such as
      longer surgical time and the increased risk of capsular rupture as compared to
      phacoemulsification done alone. In this review, different hypotheses proposed by
      different authors in their studies and possible measures that are known so far to
      prevent post-vitrectomy NSC are discussed along with its treatments and their
      complications. Moreover, we aim to describe the pathophysiology of the formation
      of post-vitrectomy NSC.

PMID- 29373809
TI  - Pressing diseases that represent promising targets for gene therapy.
AB  - Over time, there has been a growing interest in the application of gene therapy
      within the healthcare industry as demonstrated by the nearly 3,000 clinical
      trials associated with gene therapy that are listed in clinicaltrials.gov.
      However, there are various difficulties associated with gene therapy that have
      limited the realization of licensed gene therapies to only a handful of
      treatments. Furthermore, efforts to develop gene therapeutics have been narrowly
      focused and most clinical trials have sought to develop treatments for cancer
      (64.6%), monogenic diseases (10.5%), infectious diseases (7.4%), and
      cardiovascular diseases (7.4%). In addition, nearly 70% of clinical trials have
      utilized viral-based delivery systems, despite various concerns associated with
      this strategy. Each of these factors highlights the lack of diversity in the
      development of gene therapeutics that should be addressed. In recent years,
      developments in gene manipulation and delivery such as CRISPR and non-viral
      vectors (e.g., liposomes) demonstrate promise for improving outcomes for gene
      therapy. The increased fidelity and capacity afforded by these technologies
      provide the potential to improve upon contemporary gene therapy approaches and
      enable the development of treatments for less-emphasized disorders. In this
      review, we provide a summary of gene delivery technology and discuss various
      developments in gene therapy technology. We conclude by proposing several genetic
      conditions that represent promising targets for gene therapy given recent
      developments in gene delivery and manipulation.

PMID- 29373811
TI  - Long non-coding RNA CASC2 regulates Sprouty2 via functioning as a competing
      endogenous RNA for miR-183 to modulate the sensitivity of prostate cancer cells
      to docetaxel.
AB  - Prostate cancer (PC) is the most common cancer in men; however, limited effect is
      obtained due to the therapy resistance. CASC2 acts as a tumor suppressor in human
      malignancies serving as a ceRNA for miRNAs; Sprouty2 (SPRY2), a key antagonist of
      RTK signalling, also serves as a tumor suppressor. Herein, CASC2 and SPRY2
      expression was down-regulated in PC tissues and cell lines; the overexpression of
      CASC2 and SPRY2 could suppress PC cell proliferation, promote PC cell apoptosis,
      and enhance the sensitivity of PC cells to docetaxel. CASC2 positively regulated
      SPRY2 expression and inhibited downstream extracellular regulated protein kinases
      (ERK) signaling activation through SPRY2. By using online tools, miR-183 might be
      a direct target of CASC2, and might simultaneously bind to the 3'UTR of SPRY2.
      The direct binding between CASC2, miR-183 and SPRY2 was then validated; miR-183
      inhibition enhanced the cytotoxicity of docetaxel on PC cells, which could be
      partially attenuated by SPRY2 knockdown. In summary, CASC2 competes with SPRY2
      for miR-183 binding to rescue the expression of SPRY2 in PC cells, thus enhancing
      the sensitivity of PC cells to docetaxel through SPRY2 downstream ERK signaling
      pathway; CASC2 and SPRY2 might be novel adjuvants for docetaxel-based
      chemotherapy for PC.

PMID- 29373812
TI  - Journey of sperms from production by males to storage by queens in Crematogaster
      osakensis (Hymenoptera: Formicidae).
AB  - Ants show a unique reproductive system among insects. Males finish sperm
      production, and their testes degenerate at a young stage. After copulation,
      spermatozoa are transferred into the queens, who store the received sperm cells
      throughout their long lifespan without additional mating. In the present study,
      we investigated the reproductive biology of Crematogaster osakensis from male
      sexual maturation to sperm transfer, and sperm storage in queens. The sperm
      production was completed by eclosion and all produced spermatozoa had migrated to
      the seminal vesicle and the testes shrank until 10 days after eclosion. Sperm
      were not connected with bundles in mature males. The sperm cells were immobilized
      in the seminal vesicle. The sperm cells with the spermatophore were ejaculated
      into the bursa copulatrix and remained immotile during transfer from the bursa
      copulatrix to the spermathecal reservoir via the spermathecal duct. These
      findings provide significant insights into the importance of sperm
      immobilization, which prevents sperm damage and/or production of reactive oxygen
      species rather than swimming faster competed with rival male spermatozoa to reach
      into the sperm storage site, even in the polyandrous species, C. osakensis.
      Immobilization was also observed in the spermathecal reservoir 5 years after
      mating. This observation suggests that sperm immobilization is one of the
      important factors for successful long-term sperm storage and maintaining low
      levels of sperm metabolism.

PMID- 29373810
TI  - Long-term T cell responses in the brain after an ischemic stroke.
AB  - Stroke, which occurs during a loss of blood flow to the brain, is a global
      disease that accounts for 10% of yearly mortality. But stroke is also a leading
      cause of long-term adult disability, with recovery continuing for months to years
      after initial stroke onset. This long-term functional recovery from stroke
      encompasses changes in neuronal structure and function, and occurs throughout the
      post-stroke brain. Much less understood is whether the adaptive immune cells that
      infiltrated the brain during acute post-stroke neuroinflammation remain long
      term, and if their presence supports or hinders functional recovery. Studies show
      that T cell subsets and their derived cytokines exhibit diverse protective and
      detrimental effects in the immediate acute phase following stroke. Interestingly,
      T cells are also important in regulating physiological behavior, which hints at a
      potential role in functional recovery after stroke. Moreover, T cell egress into
      the post-stroke brain might actually peak weeks after stroke onset, suggesting a
      long-term role for the adaptive immune system in the injured CNS. However, the
      significance of T cells in the long-term functional and behavioral recovery and
      repair phase of stroke remains largely unexplored. We summarize here recent work
      in delineating the beneficial and detrimental effects of T cells after a stroke,
      including antigen-specific and non-specific effects of T cells in the post-stroke
      recovery phase. We also highlight the role of T cells in other CNS diseases that
      may suggest mechanisms for future study of these adaptive immune cells in the
      ischemic brain.

PMID- 29373813
TI  - Functional regulation of large conductance Ca2+-activated K+ channels in vascular
      diseases.
AB  - The large conductance Ca2+-activated potassium channels, the BK channels, is
      widely expressed in various tissues and activated in a Ca2+- and voltage
      dependent manner. The activation of BK channels hyperpolarizes vascular smooth
      muscle cell membrane potential, resulting in vasodilation. Under
      pathophysiological conditions, such as diabetes mellitus and hypertension,
      impaired BK channel function exacerbates vascular vasodilation and leads to organ
      ischemia. The vascular BK channel is composed of 4 pore-forming subunits, BK
      alpha together with 4 auxiliary subunits: beta1 subunits (BK-beta1) or gamma1
      subunits (BK-gamma1). Recent studies have shown that down-regulation of the BK
      beta1 subunit in diabetes mellitus induced vascular dysfunction; however, the
      molecular mechanism of these vascular diseases is not well understood. In this
      review, we summarize the potential mechanisms regarding BK channelopathy and the
      potential therapeutic targets of BK channels for vascular diseases.

PMID- 29373814
TI  - Behavioral and endocrine responses to season and social dynamics of captive male
      southern hairy-nosed wombats (Lasiorhinus latifrons).
AB  - Although southern hairy-nosed wombats (SHN wombats; Lasiorhinus latifrons) rarely
      breed in captivity, further knowledge of their reproductive physiology and
      behavior is likely to improve their breeding potential. This study examined the
      effect of seasonal variation and changes in social dynamics on the physiology and
      behavior of a captive population of male SHN wombats (n = 6). Seasonal changes in
      urinary testosterone metabolites (UTM), urinary cortisol metabolites (UCM),
      qualitative estimates of spermatorrhoea (QS), aggressive behavior and
      reproductive behavior were measured over an 11-month period. While there was no
      effect of month on QS (GLM ANOVA, P = 0.27), reproductive behavior (GLM ANOVA, P
      = 0.19) or aggressive behavior (Tukey pairwise comparisons), the secretion of UTM
      (GLM ANOVA, P = 0.051) was only marginally affected by season, compared to that
      reported for wild male SHN wombats. Mean UCM concentrations of July and August
      2016 were significantly higher than those between October 2015 and January 2016
      (Tukey pairwise comparisons). To examine social dynamics, two trials of animal
      positioning exchange with the enclosure system were implemented and behavioral
      data were examined for each trial over a six week period; UTM, UCM and general
      behaviors (n = 27) were measured for each trial. Neither UTM nor UCM
      concentration varied significantly (P >= 0.45) before and after the exchanges.
      "Scratching" decreased at the group level following the animal exchange in both
      trials, suggesting reduction in self-grooming may be a behavioral response to
      novel stimuli. UCM and UTM concentrations were both positively correlated with
      "standing still" and "body rub" behaviors. This may be evidence of a hormonal
      control of a "freezing behavioral response" to external stimuli and marking
      behavior, respectively. As there was no evidence that changing the social
      dynamics affected reproductive or agonistic behavior or hormone concentrations,
      it was concluded that captive male wombats in this study showed reduced
      reproductive seasonality compared to wild wombats and that animal exchange
      resulted in a behavioral response to novel stimuli but was not sufficient to
      affect testosterone or cortisol secretion, within the context of our study.

PMID- 29373815
TI  - Sphingosine-1-phosphate (S1P) activates STAT3 to protect against de novo acute
      heart failure (AHF).
AB  - AIMS: Acute heart failure (AHF) is a burden disease, with high mortality and re
      hospitalisations. Using an ex-vivo model of AHF, we have previously reported that
      sphingosine-1-phosphate (S1P) confers cardioprotection. However, the mechanisms
      remain to be elucidated. In the present study, we aimed to examine the role of
      the cardioprotective signal transducer and activator of transcription 3 (STAT3)
      in S1P mediated improved functional recovery in AHF. MATERIAL AND METHODS:
      Isolated hearts from male Long-Evans rats were subjected to hypotensive AHF for
      35 min followed by a recovery phase of 30 min (n >= 4/group). S1P (10 nM) was
      given during either the hypotensive or the recovery phase with/without an
      inhibitor of STAT3, AG490. Functional parameters were recorded throughout the
      experiment. KEY FINDINGS: Following an AHF insult, S1P, given during the recovery
      phase, improved the heart rate (HR) compared to the control (175.2 +/- 30.7 vs.
      71.6 +/- 27.4 beats per minute (BPM); p < 0.05), with no changes in the left
      ventricular developed pressure. This effect was associated with an increase in
      phosphorylated STAT3 levels in the nucleus. Addition of AG490 with S1P abolished
      the cardioprotective effect of S1P (42.3 +/- 17.1 vs. 148.8 +/- 26.4 BPM for S1P;
      p < 0.05). SIGNIFICANCE: Our data suggest that S1P protects in an ex-vivo rat
      heart model of AHF by activation of STAT3 and provide further evidence for the
      usage of S1P as a potential therapy in patients suffering from AHF.

PMID- 29373816
TI  - Extracellular vesicle therapeutics for liver disease.
AB  - Extracellular vesicles (EVs) are endogenous nanoparticles that play important
      roles in intercellular communication. Unmodified and engineered EVs can be
      utilized for therapeutic purposes. For instance, mesenchymal stem cell (MSC)
      derived EVs have shown promise for tissue repair, while drug-loaded EVs have the
      potential to be used for cancer treatment. The liver is an ideal target for EV
      therapy due to the intrinsic regenerative capacity of hepatic tissue and the
      tropism of systemically injected nanovesicles for this organ. This review will
      give an overview of the potential of EV therapeutics in liver disease.
      Specifically, the mechanisms by which MSC-EVs induce liver repair will be
      covered. Moreover, the use of drug-loaded EVs for the treatment of hepatocellular
      carcinoma will also be discussed. Although there are several challenges
      associated with the clinical translation of EVs, these biological nanoparticles
      represent a promising new therapeutic modality for liver disease.

PMID- 29373817
TI  - trans-Resveratrol ameliorates anxiety-like behaviors and fear memory deficits in
      a rat model of post-traumatic stress disorder.
AB  - trans-Resveratrol, a natural polyphenol enriched in grape seed and skin, has been
      extensively investigated for its antioxidant, anti-inflammatory and anti
      psychiatric properties. The present study examined the effects of trans
      resveratrol on ameliorating anxiety-like behaviors and fear memory deficits
      induced by time-dependent sensitization (TDS) procedure, which is a classical
      animal model for mimicking posttraumatic stress disorder (PTSD). The results
      suggested that trans-resveratrol at doses of 10, 20 and 40 mg/kg (via gavage,
      i.g.) reversed TDS-induced decreases in the percentage of time spent in the
      center of arena, the open arm entries and time spent in the open arms in the open
      field and elevated plus maze tests. It also decreased the percentage of freezing
      time in the contextual fear paradigm that was increased in TDS treated rats.
      Further study suggested that TDS-induced abnormality in the limbic hypothalamus
      pituitary-adrenal gland (L-HPA) axis was reversed by trans-resveratrol, i.e. it
      reversed increased adrenal gland index and corticotropin-releasing factor (CRF)
      levels, and rescued the differential expression of glucocorticoid receptor (GR)
      in the hypothalamus, hippocampus and amygdala. Neurobiological studies suggested
      that trans-resveratrol increased phosphorylation of cAMP response element binding
      protein (pCREB) and brain derived neurotrophic factor (BDNF) levels, which were
      decreased in rats subjected to TDS. These results provide compelling evidence
      that trans-resveratrol protects neurons against PTSD-like stress insults by
      regulation of L-HPA axis function and activation of downstream neuroprotective
      molecules, such as pCREB and BDNF expression.

PMID- 29373818
TI  - A novel fibrinolytic serine metalloprotease from the marine Serratia marcescens
      subsp. sakuensis: Purification and characterization.
AB  - This study demonstrates the purification and characterization of a fibrinolytic
      serine metalloprotease from the marine Serratia marcescens subsp. sakuensis
      (KU296189.1). The purified enzyme (1033 U/mg) had a molecular weight of 43 KDa,
      with optimum pH and temperature being 7 and 55  degrees C. The in vitro half-life
      of the fibrinolytic enzyme at 37  degrees C was found to be 19 h. The kinetic
      constants, Km and Vmax of the purified enzyme determined using fibrin as
      substrate was 0.66 mg/mL and 158.73 U/mL. The Kcat and catalytic efficiency of
      the enzyme was found to be 12.21 min-1 and 18.32 mL/(mg min) respectively. The
      fibrinolytic enzyme did not show any proteolytic activity towards blood plasma
      proteins like haemoglobin, gamma-globulins and transferrin. In vitro studies
      revealed that the fibrinolytic enzyme displayed 38% clot lysis for a period of 3
      h which was higher than that displayed by streptokinase and heparin. A total of
      seven peptide sequences were obtained after the LC-MS/MS-TOF analysis, out of
      which only four sequences showed 67% homology with the sequences of the other
      proteases. All these results suggest its novelty and potential application in
      thrombolytic therapy.

PMID- 29373819
TI  - Beliefs about FDA tobacco regulation, modifiability of cancer risk, and tobacco
      product comparative harm perceptions: Findings from the HINTS-FDA 2015.
AB  - Smokers who inaccurately believe that FDA evaluates cigarettes for safety hold
      lower harm perceptions of cigarettes compared to those who do not hold this
      belief. However, not much is known about associations between beliefs about FDA
      tobacco regulatory authority and comparative harm perceptions of tobacco
      products. Data were analyzed from the Health Information National Trends Survey,
      HINTS-FDA 2015 (N = 3738), which is a cross-sectional, probability-based,
      nationally representative survey of U.S. non-institutionalized civilian adults
      aged 18 years or older. Weighted multinomial and logistic regression analyses
      regressed comparative harm perceptions on sociodemographic factors, beliefs about
      FDA regulatory authority, perceptions of FDA credibility, and beliefs about
      modifiability of cancer risk (behavioral cancer causal beliefs and cancer
      fatalism). Findings indicate that, compared to non-users, current tobacco users
      are more likely to report believing that e-cigarettes are less harmful than
      cigarettes, to report believing that some cigarette types may be less harmful
      than others, and to report believing that tobacco products are safer now than
      they were five years ago. Awareness of FDA regulatory authority was associated
      with reporting the belief that tobacco products are safer now than five years
      ago, that e-cigarettes are less harmful than cigarettes, and that some cigarette
      types are less harmful than other cigarette types. Believing behavior as a cause
      of cancer and endorsing cancer fatalism were associated with uncertainty of
      comparative harm perceptions. Communication efforts can help target inaccurate
      beliefs by raising awareness about regulation of tobacco products as well as the
      risks of tobacco products.

PMID- 29373820
TI  - Molecular detection of Leishmania (Leishmania) infantum in phlebotomine sandflies
      from a visceral leishmaniasis endemic area in northwestern of Sao Paulo State,
      Brazil.
AB  - This study identified the natural infection rate of Leishmania (Leishmania)
      infantum in Lutzomyia longipalpis sandflies collected in a neighborhood around a
      kennel, in Dracena, northwestern of Sao Paulo state. This region is highly
      endemic for visceral leishmaniasis in Brazil. Insects were captured during 2-3
      nights monthly for 11 months (January-November 2012) using 10 automatic light
      traps around a kennel in a transition between periurban and urban neighborhood.
      Capture aimed the determination of the minimal infection rate (MIR) on the area.
      A total of 1690 Lu. longipalpis were captured during the studied period. Out of
      them, 292 (17.25%) were females and were grouped in 165 pools containing 1 to
      five insects for DNA extraction and PCR analysis. Positive results for L. (L)
      infantum in conventional PCR and real time PCR were shown in 7.28% (12/165) and
      4.85% (8/165) of the analysis respectively. These data confirm that Lu.
      longipalpis captured in the study area were infected by L. (L.) infantum. The MIR
      of sandflies during the 11 months of captures was 4.10% for female the total of
      292 female sandflies collected. A high DNA concentration of L. (L.) infantum was
      detected on sandflies especially in kennel, chicken coop and neighboring houses,
      where higher abundance of hosts for blood source were present.

PMID- 29373821
TI  - Pharyngeal Airway Space Changes After Condylar Replacement and Mandibular
      Advancement Surgery.
AB  - PURPOSE: The aim of this study was to examine the total volume and cross
      sectional areas of the pharyngeal airway after bilateral condylar replacement and
      mandibular advancement surgery. MATERIALS AND METHODS: A total of 137 patients
      (126 women and 11 men) underwent bilateral temporomandibular joint total joint
      replacement performed by 1 surgeon. A subsample of 30 patients who underwent
      condylar replacement and only mandibular advancement were evaluated for impact on
      the airway. Measurements were taken preoperatively, postoperatively, and at a
      follow-up 1 year after surgery on cone beam computed tomography scans.
      InVivoDental 3-dimensional imaging (Anatomage, San Jose, CA) was used to measure
      airway space regarding total volume (in cubic centimeters); minimum cross
      sectional area (in square millimeters); minimum cross sections of the first,
      second, and third cervical vertebrae; and whether the patient had mandibular
      retrognathia before surgery. A second operator was used to test for interoperator
      error. Descriptive and bivariate statistics were computed, and the P value was
      set at .05. RESULTS: There was a significant increase in all measurements at the
      follow-up visit compared with the preoperative visit. There were no significant
      differences between groups based on simultaneous Le Fort I surgery, mandibular
      retrognathia, and gender. However, there were statistically significant
      differences in cross sections 1 and 2, as well as minimum cross-sectional area,
      regarding age. Condylar replacement and mandibular advancement have a significant
      association with an increase in airway space. The intraclass correlation
      coefficient showed excellent agreement between interoperator measurements.
      CONCLUSIONS: Patients undergoing bilateral temporomandibular joint replacement
      and mandibular advancement surgery showed an increase in pharyngeal airway space
      at a 1-year follow-up. In this study, age was significantly associated with the
      cross-sectional areas of the airway, with older patients having smaller values.

PMID- 29373822
TI  - Electrophysiological individual face adaptation effects with fast periodic visual
      stimulation resist long interruptions in adaptation.
AB  - This study used fast periodic visual stimulation (FPVS) and
      electroencephalography (EEG) to investigate whether the reduction of face
      adaptation effects over time is due to the introduction of a novel stimulus. In
      adapting sequences, one individual face was presented at a rate of 6 Hz over 60
      s. In testing sequences this adapted face was alternated with a novel individual
      face at the same rate for 20 s, so that face identity was repeated at a frequency
      of 3 Hz (i.e. 6 Hz/2). Testing sequences started immediately or 9-15 s after
      adapting sequences. Identity adaptation produced a selective response at 3 Hz
      over the right occipito-temporal cortex both with and without delay after
      adapting sequences. These results suggest that the adaptation effect persists for
      several seconds, and that the decay of the adaptation effect is due to the
      introduction of a novel face stimulus.

PMID- 29373823
TI  - Angiography Before Posterior Mediastinal Tumor Resection: Selection Criteria and
      Patient Outcomes.
AB  - BACKGROUND: Resection of posterior mediastinal tumors may be complicated by
      bleeding or neurologic injury. Preoperative spinal angiography of mediastinal
      tumors has been underreported or not commonly practiced. This study evaluated the
      selection criteria and outcomes of patients with posterior mediastinal tumors who
      underwent preoperative angiography and embolization. METHODS: This was a single
      institution retrospective study of patients with posterior mediastinal tumors
      from 2002 to 2016. Multilevel spinal angiography was performed, with or without
      selective arterial embolization of vascular supply, in patients selected by
      thoracic or neurologic surgeons. RESULTS: Ten of 87 patients (11%) with posterior
      mediastinal tumors underwent preoperative angiography. A mean of 11 arteries
      (range, 2 to 25) were studied. Embolization in 7 of 10 patients successfully
      occluded 1 to 3 arteries. There was no significant difference in age, sex, body
      mass index, American Society of Anesthesiologists Physical Status Classification,
      operative time, operative blood loss, complications, or death between patients
      with or without angiography. Patients who underwent angiography had larger tumors
      (1,490 vs 97 cm3, p < 0.0001), involvement of the neuroforamen (44% vs 10%, p <
      0.05), and a longer hospital stay (9 vs 4.5 days, p < 0.05). Angiography was
      complicated in 1 patient by vocal cord ulceration after intubation of a tumor
      compressed trachea. Shared blood supply between the tumor and the spinal cord
      precluded embolization and tumor resection in 1 patient. Use of angiography
      increased over time. CONCLUSIONS: Selective preoperative angiography for
      evaluation of posterior mediastinal tumors identifies arterial variations,
      threatened spinal arteries, and targets for embolization. The specific role of
      angiography and embolization requires further investigation to standardize
      indications and protocols for the number of arteries examined.

PMID- 29373824
TI  - Amplatzer Device Embolization to the Aortic Arch Discovered Two Years After
      Implantation.

PMID- 29373825
TI  - Postoperative Complications Drive Unplanned Readmissions After Esophagectomy for
      Cancer.
AB  - BACKGROUND: Hospital readmissions are increasingly viewed as a marker of inferior
      health care quality and penalized with decreased reimbursement. The timing of,
      and reasons for, readmissions after esophagectomy for cancer are not well
      understood. We examined the association of complications to 30-day postoperative
      related, unplanned readmission to identify opportunities for improvement in
      patient care. METHODS: We analyzed the American College of Surgeons National
      Surgical Quality Improvement Program database (2012 to 2015) to characterize 30
      day postoperative unplanned readmissions after esophagectomy for cancer using
      descriptive statistics. Type and timing of readmission after discharge was
      assessed. A Cox proportional hazards model was developed to identify predictors
      of readmission. RESULTS: Of 3,723 patients who underwent esophagectomy for
      cancer, 1,419 (38.1%) experienced >=1 complication within 30 days. A total of 400
      patients (10.7%) experienced related, unplanned readmissions within 30 days of
      the operation, and postoperative complications were documented in 263 (65.8%).
      Leading causes of readmission were infectious, pulmonary, and gastrointestinal
      complications. Of these patients, 155 (59%) were readmitted within 7 days and 236
      (90%) within 14 days of discharge. The Cox proportional hazards model identified
      readmission being associated with occurrence of postdischarge infectious,
      pulmonary, venous thromboembolic, and urinary tract infection complications, in
      hospital urinary tract infection complications, and log-transformation of length
      of stay (representing increasing length of stay) (all p < 0.05). CONCLUSIONS:
      Postoperative occurrence of common complications and prolonged length of stay are
      associated with unplanned readmission after esophagectomy. Most patients are
      readmitted within 1 week of discharge. Earlier follow-up after discharge may
      identify patients with complications and facilitate outpatient intervention to
      prevent readmission.

PMID- 29373826
TI  - An Element of Life.
AB  - While it has been known for decades that the essential function of selenium was
      in the form of its incorporation as selenocysteine into selenoproteins-including
      the enzyme glutathione peroxidase-4-now, Ingold et al. (2018) reveal the precise
      role of selenolate-based catalysis by this enzyme.

PMID- 29373827
TI  - Meiotic Recombination: Genetics' Good Old Scalpel.
AB  - In the era of genome engineering, a new study returns to classical genetics to
      decipher genotype-phenotype relationships in unprecedented throughput and with
      unprecedented accuracy. Capitalizing on natural variation in yeast strains and
      frequent meiotic recombination, She and Jarosz (2018) dissect and map to
      nucleotide resolution, simple and complex determinants of diverse phenotypic
      traits.

PMID- 29373830
TI  - Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor.
AB  - KRASG12C was recently identified to be potentially druggable by allele-specific
      covalent targeting of Cys-12 in vicinity to an inducible allosteric switch II
      pocket (S-IIP). Success of this approach requires active cycling of KRASG12C
      between its active-GTP and inactive-GDP conformations as accessibility of the S
      IIP is restricted only to the GDP-bound state. This strategy proved feasible for
      inhibiting mutant KRAS in vitro; however, it is uncertain whether this approach
      would translate to in vivo. Here, we describe structure-based design and
      identification of ARS-1620, a covalent compound with high potency and selectivity
      for KRASG12C. ARS-1620 achieves rapid and sustained in vivo target occupancy to
      induce tumor regression. We use ARS-1620 to dissect oncogenic KRAS dependency and
      demonstrate that monolayer culture formats significantly underestimate KRAS
      dependency in vivo. This study provides in vivo evidence that mutant KRAS can be
      selectively targeted and reveals ARS-1620 as representing a new generation of
      KRASG12C-specific inhibitors with promising therapeutic potential.

PMID- 29373829
TI  - Mapping Causal Variants with Single-Nucleotide Resolution Reveals Biochemical
      Drivers of Phenotypic Change.
AB  - Understanding the sequence determinants that give rise to diversity among
      individuals and species is the central challenge of genetics. However, despite
      ever greater numbers of sequenced genomes, most genome-wide association studies
      cannot distinguish causal variants from linked passenger mutations spanning many
      genes. We report that this inherent challenge can be overcome in model organisms.
      By pushing the advantages of inbred crossing to its practical limit in
      Saccharomyces cerevisiae, we improved the statistical resolution of linkage
      analysis to single nucleotides. This "super-resolution" approach allowed us to
      map 370 causal variants across 26 quantitative traits. Missense, synonymous, and
      cis-regulatory mutations collectively gave rise to phenotypic diversity,
      providing mechanistic insight into the basis of evolutionary divergence. Our data
      also systematically unmasked complex genetic architectures, revealing that
      multiple closely linked driver mutations frequently act on the same quantitative
      trait. Single-nucleotide mapping thus complements traditional deletion and
      overexpression screening paradigms and opens new frontiers in quantitative
      genetics.

PMID- 29373828
TI  - Functional Classification and Experimental Dissection of Long Noncoding RNAs.
AB  - Over the last decade, it has been increasingly demonstrated that the genomes of
      many species are pervasively transcribed, resulting in the production of numerous
      long noncoding RNAs (lncRNAs). At the same time, it is now appreciated that many
      types of DNA regulatory elements, such as enhancers and promoters, regularly
      initiate bi-directional transcription. Thus, discerning functional noncoding
      transcripts from a vast transcriptome is a paramount priority, and challenge, for
      the lncRNA field. In this review, we aim to provide a conceptual and experimental
      framework for classifying and elucidating lncRNA function. We categorize lncRNA
      loci into those that regulate gene expression in cis versus those that perform
      functions in trans and propose an experimental approach to dissect lncRNA
      activity based on these classifications. These strategies to further understand
      lncRNAs promise to reveal new and unanticipated biology with great potential to
      advance our understanding of normal physiology and disease.

PMID- 29373832
TI  - Nudt21 Controls Cell Fate by Connecting Alternative Polyadenylation to Chromatin
      Signaling.

PMID- 29373831
TI  - Context-Dependent and Disease-Specific Diversity in Protein Interactions within
      Stress Granules.
AB  - Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form
      during cellular stress and are increasingly implicated in human
      neurodegeneration. To study the proteome and compositional diversity of SGs in
      different cell types and in the context of neurodegeneration-linked mutations, we
      used ascorbate peroxidase (APEX) proximity labeling, mass spectrometry, and
      immunofluorescence to identify ~150 previously unknown human SG components. A
      highly integrated, pre-existing SG protein interaction network in unstressed
      cells facilitates rapid coalescence into larger SGs. Approximately 20% of SG
      diversity is stress or cell-type dependent, with neuronal SGs displaying a
      particularly complex repertoire of proteins enriched in chaperones and autophagy
      factors. Strengthening the link between SGs and neurodegeneration, we demonstrate
      aberrant dynamics, composition, and subcellular distribution of SGs in cells from
      amyotrophic lateral sclerosis (ALS) patients. Using three Drosophila ALS/FTD
      models, we identify SG-associated modifiers of neurotoxicity in vivo. Altogether,
      our results highlight SG proteins as central to understanding and ultimately
      targeting neurodegeneration.

PMID- 29373833
TI  - SnapShot: O-Glycosylation Pathways across Kingdoms.
AB  - O-glycosylation is one of the most abundant and diverse types of post
      translational modifications of proteins. O-glycans modulate the structure,
      stability, and function of proteins and serve generalized as well as highly
      specific roles in most biological processes. This ShapShot presents types of O
      glycans found in different organisms and their principle biosynthetic pathways.
      To view this SnapShot, open or download the PDF.

PMID- 29373834
TI  - New zwitterionic monoterpene indole alkaloids from Uncaria rhynchophylla.
AB  - Four new zwitterionic monoterpene indole alkaloids, rhynchophyllioniums A-D (1
      4), together with eight known alkaloids (5-12), were isolated from the hook
      bearing stems of Uncaria rhynchophylla. Their structures were elucidated by
      extensive spectroscopic data analysis of MS, 1D and 2D NMR, and ECD, and the
      zwitterionic forms and absolute configurations of 1 and 2 were unambiguously
      confirmed by single crystal X-ray diffraction analysis. All the isolates,
      including the monoterpene indole alkaloids with free C-22 carboxyl group and
      those with C-22 carboxyl methyl ester, were proved to be naturally coexisting in
      the herb by LC-MS analysis. This is the first report of monoterpene indole
      alkaloids that exist in the form of zwitterion. Additionally, the cytotoxic
      activities of all isolates against A549, HepG2, and MCF-7 cell lines are
      reported.

PMID- 29373835
TI  - The in vitro detection of botulinum neurotoxin-cleaved endogenous VAMP is epitope
      dependent.
AB  - The in vitro potency of botulinum neurotoxin (BoNT) serotypes is often measured
      by monitoring cleavage of their soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) protein substrates. A frequently used method
      is Western blot, whereby the full-length protein and cleaved form migrate at
      different molecular weights. Until now, it has been extremely difficult to detect
      the cleaved cellular form of the SNARE protein vesicle associated membrane
      protein 1, 2 or 3 (VAMP1, 2 or 3) by Western blot. These VAMP isoforms are the
      substrates of BoNT serotypes BoNT/B, D, F and G as well as tetanus neurotoxin.
      Using custom made anti-VAMP antibodies against epitopes either side of the
      cleavage sites for BoNT/B, BoNT/D and BoNT/F, we have successfully detected the
      cleaved C-terminal VAMP fragment in cortical neurons. These new antibodies enable
      quantitative assessment of the potency of VAMP-cleaving neurotoxins by a gain of
      signal Western blot assay.

PMID- 29373836
TI  - Patients' perceived needs of health care providers for low back pain management:
      a systematic scoping review.
AB  - BACKGROUND CONTEXT: Optimal management of low back pain (LBP) involves patients'
      active participation in care, facilitated by positive interactions with their
      health care provider(s) (HCP). An understanding of patients' perceived needs
      regarding their HCP is, therefore, necessary to achieve such outcomes. Therefore,
      the aim of the present study is to review the existing literature regarding
      patients' perceived needs of HCP managing LBP. METHODS: A systematic scoping
      review of publications in MEDLINE, EMBASE, CINAHL, and PsycINFO (1990-2016) was
      performed. Descriptive data regarding study design and methodology were
      extracted, and risk of bias was assessed. Aggregates of patients' perceived needs
      of HCP for LBP were categorized. RESULTS: Forty-three studies (30 qualitative, 12
      quantitative, and 1 mixed methods) from 1,829 were relevant. Four areas of
      perceived need emerged: (1) there are several characteristics of HCP that
      patients desire, such as good communication and shared decision-making; (2)
      patients wanted HCP to provide information, including a cause of their LBP and
      legitimization of their symptoms; (3) patients' valued holistic, individualized
      care, and continuity of care; and (4) patients perceived long waiting times,
      difficulties with access to treatment, cost, and personal effort to be obstacles
      to care. CONCLUSIONS: Patients with LBP want patient-centered care, to be
      actively involved, and they have identified characteristics of HCP that foster a
      good provider-patient relationship. They noted areas of dissatisfaction with HCP
      and perceived obstacles to care. Given limited health care resources, HCP and
      policy makers need to implement novel methods of health care delivery that
      address these issues to facilitate improved patient satisfaction and achieve
      better patient and health system outcomes.

PMID- 29373837
TI  - Evaluation of five automated and one manual method for Toxoplasma and human DNA
      extraction from artificially spiked amniotic fluid.
AB  - OBJECTIVES: Molecular detection of Toxoplasma gondii plays a crucial role in the
      prenatal and neonatal diagnosis of congenital toxoplasmosis (CT). Sensitivity of
      this diagnosis is partly related to the efficiency of parasite DNA extraction and
      amplification. DNA extraction methods with automated platforms have been
      developed. Therefore, it is essential to evaluate them in combination with
      adequate PCR amplification assays. METHODS: In this multisite study, we
      investigated the suitability of two recent automated procedures for the isolation
      of Toxoplasma DNA from amniotic fluid (AF) (Magtration system 12GC, PSS and
      Freedom EVO VacS, Tecan), compared with three other automated procedures
      (MagNAPure Compact, Roche, BioRobot EZ1, Qiagen and modified NucliSens easyMAG,
      bioMerieux) and with the manual DNA extraction QIAamp DNA Mini kit (Qiagen). Two
      Toxoplasma PCR assays targeting the '529-bp' repeat DNA element were used, based
      upon dual hybridization (FRET) or hydrolysis (TaqMan) probes. A total of 1296
      PCRs were performed including 972 Toxoplasma PCRs. RESULTS: We showed variable
      efficacy (4.2%-100% positive results) among the DNA extraction procedures in
      isolating up to five T. gondii cells/mL in AF samples. Moreover, for a given DNA
      extraction method, variable results were obtained among the two Toxoplasma PCR
      assays for detecting up to five T. gondii cells/mL: when using TaqMan PCR, all
      the automated systems yielded more than 60% positive results. Nevertheless, when
      testing the DNA extracts in triplicate, four out of six extraction methods
      allowed a satisfactory detection of low amounts of T. gondii DNA (>=33% of
      positive results) independently of the PCR assay used. CONCLUSIONS: Despite the
      influence of the subsequent PCR method used, this study should help
      microbiologists in the choice of DNA extraction methods for the detection of T.
      gondii in amniotic fluid. The extraction method should be checked as adequate for
      the PCR assay used.

PMID- 29373838
TI  - Quantifying multiple sclerosis pathology in post mortem spinal cord using MRI.
AB  - Multiple sclerosis (MS) is a common inflammatory, demyelinating and degenerative
      disease of the central nervous system. The majority of people with MS present
      with symptoms due to spinal cord damage, and in more advanced MS a clinical
      syndrome resembling that of progressive myelopathy is not uncommon. Significant
      efforts have been undertaken to predict MS-related disability based on short-term
      observations, for example, the spinal cord cross-sectional area measured using
      MRI. The histo-pathological correlates of spinal cord MRI changes in MS are
      incompletely understood, however a surge of interest in tissue microstructure has
      recently led to new approaches to improve the precision with which MRI indices
      relate to underlying tissue features, such as myelin content, neurite density and
      orientation, among others. Quantitative MRI techniques including T1 and T2,
      magnetisation transfer (MT) and a number of diffusion-derived indices have all
      been successfully applied to post mortem MS spinal cord. Combining advanced
      quantification of histological features with quantitative - particularly
      diffusion-based - MRI techniques provide a new platform for high-quality
      MR/pathology data generation. To more accurately quantify grey matter pathology
      in the MS spinal cord, a key driver of physical disability in advanced MS,
      remains an important challenge of microstructural imaging.

PMID- 29373840
TI  - Icariin modulates mitochondrial function and apoptosis in high glucose-induced
      glomerular podocytes through G protein-coupled estrogen receptors.
AB  - Podocyte apoptosis in glomerular lesions has been found to have a dominant role
      in the progression of diabetic nephropathy. The present research aimed to explore
      the beneficial effect of icariin on diabetic podocytes by interfering in the
      process of apoptosis. Podocyte apoptosis was significantly exacerbated after high
      glucose treatment, with the level of reactive oxygen species (ROS) increasing
      simultaneously. Here, we demonstrated that icariin, which is a G protein-coupled
      estrogen receptor 1 (GPER) agonist, inhibited podocyte apoptosis by reducing ROS,
      maintaining the integrity of mitochondrial membranes. Moreover, the stabilization
      of mitochondria by icariin was reversed when GPER was knocked down in podocytes.
      Meanwhile, icariin inhibited the caspase cascade in podocyte apoptosis by
      promoting Bcl-2 expression and mitochondrial translocation. The above findings at
      least partly elucidated the mechanism by which icariin stabilized podocytes by
      inducing the mitochondrial Bcl-2 translocation and therefore preventing
      downstream apoptosis.

PMID- 29373839
TI  - Nogo-B receptor increases the resistance of estrogen receptor positive breast
      cancer to paclitaxel.
AB  - Intrinsic or acquired chemoresistance is a hurdle in oncology. Only 7%-16% of
      estrogen receptor alpha (ERalpha) positive breast cancer cases achieve a
      pathological complete response (pCR) after neo-adjuvant chemotherapy. Nogo-B
      receptor (NgBR) is a cell surface receptor that binds farnesylated Ras and
      promotes Ras translocation to the plasma membrane. Here, we demonstrate NgBR as a
      potential therapeutic target for ERalpha positive breast cancer patients to
      attenuate paclitaxel resistance. NgBR knockdown enhanced paclitaxel-induced cell
      apoptosis by modulating expression of p53 and survivin in ERalpha positive breast
      cancer cells via NgBR-mediated PI3K/Akt and MAPK/ERK signaling pathways. NgBR
      knockdown attenuated either 17beta-estradiol or epidermal growth factor
      stimulated phosphorylation of ERalpha at Serine 118 residue. The ChIP-PCR assay
      further demonstrated that NgBR knockdown decreased ERalpha binding to the
      estrogen response element (ERE) of the ERalpha target gene and increased the
      binding of p53 to the promoter region of survivin to attenuate survivin
      transcription. In summary, our data suggest that NgBR expression is essential to
      promoting ERalpha positive breast cancer cell resistance to paclitaxel. Findings
      from this study implicate a novel therapeutic target for treating ERalpha
      positive breast cancer in neo-adjuvant/adjuvant chemotherapy.

PMID- 29373841
TI  - Recent advances in siRNA delivery for cancer therapy using smart nanocarriers.
AB  - Small interfering RNAs (siRNAs) can selectively target and downregulate disease
      causing genes, holding great promise in treating human diseases, especially
      malignant cancers. However, how to efficiently deliver siRNAs into target cell
      cytosol is a problem that has hindered their clinical application. Here, we
      review the recent strategies for siRNA delivery on the basis of smart
      nanocarriers by using stimuli-responsive materials. We highlight the rationales
      of how to design smart nanocarriers responsive to physiological and external
      stimuli to improve the delivery efficiency, targeting precision and gene
      silencing efficacy. Finally, we provide an outlook on the fundamental limitation
      for clinical translation of siRNA-based nanomedicine that should be overcome by
      the combination of chemistry, biology, material and medical science.

PMID- 29373842
TI  - Bowel Invisible Microscopic Endometriosis: Leave It Alone.

PMID- 29373843
TI  - ROS and redox signaling in myocardial ischemia-reperfusion injury and
      cardioprotection.
AB  - Ischemia-reperfusion (IR) injury is central to the pathology of major
      cardiovascular diseases, such as stroke and myocardial infarction. IR injury is
      mediated by several factors including the elevated production of reactive oxygen
      species (ROS), which occurs particularly at reperfusion. The mitochondrial
      respiratory chain and NADPH oxidases of the NOX family are major sources of ROS
      in cardiomyocytes. The first part of this review discusses recent findings and
      controversies on the mechanisms of superoxide production by the mitochondrial
      electron transport chain during IR injury, as well as the contribution of the NOX
      isoforms expressed in cardiomyocytes, NOX1, NOX2 and NOX4, to this damage. It
      then focuses on the effects of ROS on the opening of the mitochondrial
      permeability transition pore (mPTP), an inner membrane non-selective pore that
      causes irreversible damage to the heart. The second part analyzes the redox
      mechanisms of cardiomyocyte mitochondrial protection; specifically, the
      activation of the hypoxia-inducible factor (HIF) pathway and the antioxidant
      transcription factor Nrf2, which are both regulated by the cellular redox state.
      Redox mechanisms involved in ischemic preconditioning, one of the most effective
      ways of protecting the heart against IR injury, are also reviewed. Interestingly,
      several of these protective pathways converge on the inhibition of mPTP opening
      during reperfusion. Finally, the clinical and translational implications of these
      cardioprotective mechanisms are discussed.

PMID- 29373844
TI  - Citrullinated fibrinogen impairs immunomodulatory function of bone marrow
      mesenchymal stem cells by triggering toll-like receptor.
AB  - Bone marrow mesenchymal stem cells (BMSC) have been shown to possess
      immunomodulatory activities, while its role in rheumatoid arthritis (RA) remains
      unknown. Citrullinated fibrinogen (cfb) has been considered as a specific
      autoantigen in RA pathogenesis. Our study aims to determine the role of cfb on
      immunomodulatory function of BMSC. We demonstrated the specific role of toll-like
      receptor 4 (TLR4)-NFkappaB pathway in the pro-inflammatory response of BMSC to
      cfb with increased production of interleukin (IL)-6, IL-8 and chemokine CC motif
      ligand 2 (CCL2). Moreover, cfb impaired BMSC-mediated suppression of peripheral
      blood mononuclear cells (PBMC) proliferation and reduced the production of the
      key immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO) in BMSC. We have
      uncovered a previously unrecognized role of cfb in interfering BMSC-mediated
      immunoregulation in RA. Cfb could act as a damage-associated molecule pattern
      (DAMP) for BMSC and thereby contribute to the propagation of inflammation in RA.

PMID- 29373845
TI  - Daptomycin treatment in Gram-positive vascular graft infections.
AB  - BACKGROUND: Daptomycin is a bactericidal antibiotic approved for the treatment of
      skin and soft tissue infections and right-side endocarditis. However, there is a
      lack of published data outlining its usefulness in vascular graft infections
      (VGI). The aim of this study was to describe the clinical experience of
      daptomycin use in the treatment of VGI caused by Gram-positive bacteria. METHODS:
      This was a retrospective cohort study of patients diagnosed with VGI receiving
      daptomycin at a tertiary care hospital during the period January 2010 to December
      2012. RESULTS: Of a total 1066 consecutive patients who had undergone vascular
      grafts (VG), 25 were diagnosed with VGI. Fifteen of these patients (11 prosthetic
      VG, three autologous VG, one both types) received daptomycin (median dose
      6.7mg/kg/day, range 4.1-7.1mg/kg/day; median age 69 years, range 45-83 years; 80%
      male). The infected bypass was removed in 13 cases. The most common reason for
      selecting daptomycin was kidney failure (53%). The Gram-positive organisms
      isolated were coagulase-negative Staphylococcus (n=10), Staphylococcus aureus
      (n=3) (two methicillin-resistant S. aureus), Enterococcus faecium (n=2), and
      Enterococcus faecalis (n=1). The mean follow-up was 69 months (interquartile
      range 48-72 months). Ten patients (66.7%) achieved complete healing of the VGI. A
      recurrence of the infection was observed in 100% of patients in whom the bypass
      was not removed. Among patients who did not achieve complete healing, one needed
      a supracondylar amputation and one died as a consequence of infection. Five
      patients received treatment with rifampicin in addition to daptomycin and they
      were all cured. CONCLUSIONS: The use of daptomycin and surgery for Gram-positive
      VGI was effective and well tolerated, and this may be a good alternative for the
      treatment of VGI in patients with peripheral arterial disease in whom renal
      insufficiency is common.

PMID- 29373846
TI  - Soluble expression of biologically active methionine sulfoxide reductase B1
      (PaMsrB1) from Carica papaya in Escherichia coli and isolation of its protein
      targets.
AB  - Plant methionine sulfoxide reductase B1 (MsrB1) protects the photosynthetic
      apparatus from oxidative damage by scavenging reactive oxygen species to repair
      Met-oxidized proteins in response to abiotic stresses and biotic attack. Papaya
      MsrB1 (PaMsrB1) was identified previously to interact with papaya ringspot virus
      NIa-Pro, and this interaction inhibits the import of PaMsrB1 into the
      chloroplast. Further functional characterization of PaMsrB1 requires the
      production of a biologically active purified recombinant protein. In this report,
      PaMsrB1 as a fusion protein containing an N-terminal maltose-binding protein
      (MBP) was expressed in Escherichia coli Rosetta (DE3) cells and purified.
      Production of soluble fusion protein was greater when the cells were cultured at
      16  degrees C than at 37  degrees C. The Factor Xa protease digested MBP-PaMsrB1
      fusion protein and subsequently purified recombinant PaMsrB1 specifically reduced
      the R-diastereomer of methionine sulfoxide (MetSO) and Dabsyl-MetSO to Met in the
      presence of dithiothreitol. Eight chloroplast-localized and five non-chloroplast
      localized candidate proteins that interact with PaMsrB1 were isolated by affinity
      chromatography and liquid chromatography coupled to tandem mass spectrometry. The
      results provide a platform to further understand the anti-oxidative defense
      mechanism of PaMsrB1.

PMID- 29373847
TI  - Housing and testing in mixed-sex rooms increases motivation and accuracy during
      operant testing in both male and female mice.
AB  - Operant behavior tasks are widely used in neuroscience research, but little is
      known about how variables such as housing and testing conditions affect rodent
      operant performance. We have previously observed differences in operant
      performance in male and female mice depending on whether mice were housed and
      tested in rooms containing only one sex versus rooms containing both sexes. Here,
      male and female mice in either single-sex or mixed sex housing rooms were trained
      on fixed ratio 1 (FR1) and progressive ratio (PR) tasks. For both sexes, animals
      in the mixed sex room had more accurate performance in FR1 and were more
      motivated in the PR task. We then moved the single sex housed animals to the
      mixed sex room and vice versa. Animals that started in mixed sex housing had no
      change to PR, but both sexes who started in single sex housing were more
      motivated after the switch. Additionally, the females that moved into single-sex
      housing performed less accurately in FR1. We conclude that housing and testing
      conditions can affect performance on FR1 and PR tasks. As these tasks are
      commonly used as training steps to more complex tasks, housing and testing
      conditions should be carefully considered during experiment design and reported
      in publications.

PMID- 29373848
TI  - On the Cusp of a Healthcare Revolution: BME Technologies Have the Potential to
      ?Transform Our World?
AB  - Of the key technologies listed as "ready to propel industries and transform our
      world" in the 2017 report Top 50 Emerging Technologies: Growth Opportunities of
      Strategic Imperative, most fall under the scope of biomedical engineering (BME).
      Issued by the major market research and analysis company Frost and Sullivan [1],
      the report's findings are no surprise to the researchers, clinicians, and others
      who are heavily invested in this field.

PMID- 29373849
TI  - Automated Insulin Delivery: Taking the Guesswork out of Diabetes Management.
AB  - For individuals with Type 1 or insulin-requiring Type 2 diabetes, new technology
      may offer something they desperately need, but is now nigh impossible: the
      ability to maintain ideal blood glucose levels all day, every day.

PMID- 29373850
TI  - Machine Learning Takes on Health Care: Leonard D'Avolio's Cyft Employs Big Data
      to Benefit Patients and Providers.
AB  - When Leonard D'Avolio (Figure 1) was working on his Ph.D. degree in biomedical
      informatics, he saw the power of machine learning in transforming multiple
      industries; health care, however, was not among them. "The reason that Amazon,
      Netflix, and Google have transformed their industries is because they have
      embedded learning throughout every aspect of what they do. If we could prove that
      is possible in health care too, I thought we would have the potential to have a
      huge impact," he says.

PMID- 29373851
TI  - Carbon Monoxide, Repurposed: Researchers Are Developing Myriad Ways to Deliver CO
      to Treat Sickle Cell Anemia, Lung Disease, and More.
AB  - In the 16th century, Paracelsus-the father of modern toxicology-wrote that "all
      things are poison and nothing is without poison; the dose alone makes a thing not
      poison." While it's conceivable that too much of a good thing, such as water or
      oxygen, could be fatal, the opposite-that smaller quantities of a bad thing might
      be beneficial-may be harder to believe. But four centuries after Paracelsus
      shared this idea, two researchers decided to apply the more counterintuitive
      notion of Paracelsus' dogma for a notoriously toxic chemical: carbon monoxide
      (CO).

PMID- 29373852
TI  - Technology You Can Swallow: Moving Beyond Wearable Sensors, Researchers Are
      Creating Ingestible Ones.
AB  - Around 6 p.m. each evening, the streets of Boston's suburbs come alive with the
      physically fit and those aspiring to be. They are runners, bikers, walkers, and
      scooter riders of all different body shapes and ages who would seem to have
      little in common except one thing-an electronic band wrapped around their wrist.
      For many of these people, it's hard to imagine life without the daily nagging
      from a personal health device to meet their daily prescript of 10,000 steps.

PMID- 29373853
TI  - Tiny Conveyance: Micro- and Nanorobots Prepare to Advance Medicine.
AB  - In the science-fiction classic Fantastic Voyage [1], a shrink-ray zaps a
      submarine and the crew within it, and the resulting microscopic vehicle ventures
      inside a human body to destroy a blood clot and save a prominent patient's life.
      While that scenario remains in the realm of make-believe, it may not be long
      before micro- and nanoscale robots can navigate a person's blood vessels and
      execute a medical task, such as the targeted delivery of drugs or even the
      performance of some medical procedures.

PMID- 29373854
TI  - A New Fight Against Colon Cancer: As Cancer Rates Rise Among Younger Adults,
      Researchers Look for New Screening and Treatment Options.
AB  - Although the overall incidence of colon cancer has been falling over the past few
      decades, a pair of recent studies revealed a startling trend. In February 2017,
      researchers published a report showing that colon cancer rates were rising among
      younger adults. Some skeptics suggested the spike might simply reflect earlier
      detection and not necessarily represent a real increase in the disease. But a
      follow-up study found that Gen-Xers and millenials aren't just getting cancer
      diagnoses earlier; they are dying from colon cancer at slightly higher rates than
      in previous decades. Death rates among adults aged 20-54 have increased slightly,
      to 4.3 deaths per 100,000 people in 2014, up from 3.9 per 100,000 in 2004.

PMID- 29373855
TI  - Toward Better Management for Asthma: From Smart Inhalers to Injections to
      Wearables, Researchers Are Finding New Ways to Improve Asthma Treatment.
AB  - Although asthma has been around since Hippocrates' time, more people are being
      diagnosed with the disease than ever before. Over the last 20 years, the global
      burden of asthma has increased by almost 30%, as more than 235 million people
      most of them children-cope with the breathlessness and wheezing characteristic of
      the disease. In particular, cases have spiked in China and India, where pollution
      is reported to sometimes be deadly. Researchers with the Health Effects
      Institute, a Boston-based nonprofit that studies the health effects of pollution,
      recently reported that air pollution in India and China alone contributed to more
      than half of the four million deaths worldwide due to air pollution in 2015.

PMID- 29373856
TI  - Black and White and Shades of Gray [State of the Art].
AB  - "Moderation in all things" is a popular saying that many of us have heard all our
      lives. Still, a good number of people seem to have forgotten the sentiment behind
      this advice. Instead of looking for the good that exists within the bad and the
      bad that dwells within the good, people are choosing to line up behind one
      extreme or another. Nuances are being ignored in favor of strong positions on
      either side of the middle. This has led inevitably to polarization, partisanship,
      and balkanization in our society. For some reason, moderation has been forgotten.

PMID- 29373857
TI  - The Brain Willis Circle and Ring Electric Power Systems: Analogies
      [Retrospectroscope].
AB  - The word analogy is a synonym of likeness, resemblance, similitude, or affinity
      and involves two concepts being placed side by side, as in a comparison [1]. The
      workings of nature and those of human societies are amenable to such analogous
      comparison-even though the evolution of the natural world obviously spans
      millions of years [2], while human societies are much younger, relatively puppies
      by comparison. This article considers two interesting examples from these two
      realms that show remarkable similarities (possibly a result of sheer chance),
      i.e., a circulatory brain anastomosis, the circle of Willis (CW), and modern
      power transmission-distribution systems in the ring arrangement. Remember that
      electric networks handle the flow of charges [say, in coulombs per second (C/s)
      or electric charge per unit time, which is current), whereas hydraulic systems
      deal with fluid flow [say, in liters per minutes (L/min) or volume/unit time or
      fluid mass/unit time]. Hence, these systems too are analogous, a well-known fact
      often mentioned by instructors of electrical engineering courses.

PMID- 29373858
TI  - Capturing Genetic Diversity: The Power of the CC and DO Mouse Models.

PMID- 29373859
TI  - Urine Arsenic and Arsenic Metabolites in U.S. Adults and Biomarkers of
      Inflammation, Oxidative Stress, and Endothelial Dysfunction: A Cross-Sectional
      Study.
AB  - BACKGROUND: Arsenic (As) exposure has been associated with increased risk for
      cardiovascular disease (CVD) and with biomarkers of potential CVD risk and
      inflammatory processes. However, few studies have evaluated the effects of As on
      such biomarkers in U.S. populations, which are typically exposed to low to
      moderate As concentrations. OBJECTIVES: We investigated associations between As
      exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk
      in a subset of participants from the New Hampshire Health Study, a population
      with low to moderate As exposure (n=418). METHODS: Associations between toenail
      As, total urine As (uAs), and %uAs metabolites [monomethyl (%uMMAV), dimethyl
      (%uDMAV), and inorganic (%iAs) species] and plasma biomarkers, including soluble
      plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1,
      respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha,
      plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15
      F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models.
      RESULTS: Covariate-adjusted estimates of associations with a doubling of urinary
      As suggested an 8.8% increase in 15-F2t-IsoP (95% CI: 3.2, 14.7), and a doubling
      of toenail As was associated with a 1.7% increase in VCAM-1 (95% CI: 0.2, 3.2).
      Additionally, a 5% increase in %uMMA was associated with a 7.9% increase in 15
      F2t-IsoP (95% CI: 2.1, 14.1), and a 5% increase in %uDMA was associated with a
      2.98% decrease in 15-F2t-IsoP [(95% CI: -6.1, 0.21); p=0.07]. However, in
      contrast with expectations, a doubling of toenail As was associated with a 2.3%
      decrease (95% CI: -4.3, -0.3) in MMP-9, and a 5% increase in %uMMA was associated
      with a 7.7% decrease (95% CI: -12.6, -2.5) in PAI-1. CONCLUSION: In a cross
      sectional study of U.S. adults, we observed some positive associations of uAs and
      toenail As concentrations with biomarkers potentially relevant to CVD
      pathogenesis and inflammation, and evidence of a higher capacity to metabolize
      inorganic As was negatively associated with a marker of oxidative stress.
      https://doi.org/10.1289/EHP2062.

PMID- 29373861
TI  - The Sister Study Cohort: Baseline Methods and Participant Characteristics.
AB  - BACKGROUND: The Sister Study was designed to address gaps in the study of
      environment and breast cancer by taking advantage of more frequent breast cancer
      diagnoses among women with a sister history of breast cancer and the presumed
      enrichment of shared environmental and genetic exposures. OBJECTIVE: The Sister
      Study sought a large cohort of women never diagnosed with breast cancer but who
      had a sister (full or half) diagnosed with breast cancer. METHODS: A multifaceted
      national effort employed novel strategies to recruit a diverse cohort, and
      collected biological and environmental samples and extensive data on potential
      breast cancer risk factors. RESULTS: The Sister Study enrolled 50,884 U.S. and
      Puerto Rican women 35-74y of age (median 56 y). Although the majority were non
      Hispanic white, well educated, and economically well off, substantial numbers of
      harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic
      white: 16%; no college degree: 35%; household income <$50,000: 26%). Although all
      had a biologic sister with breast cancer, 16.5% had average or lower risk of
      breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score).
      Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of
      age (79%), never-smokers (56%) with body mass indexes (BMIs) of <29.9 kg/m2
      (70%). Few (5%) reported any cancer prior to enrollment. CONCLUSIONS: The Sister
      Study is a unique cohort designed to efficiently study environmental and genetic
      risk factors for breast cancer. Extensive exposure data over the life-course and
      baseline specimens provide important opportunities for studying breast cancer and
      other health outcomes in women. Collaborations are welcome.
      https://doi.org/10.1289/EHP1923.

PMID- 29373860
TI  - Cadmium-Associated Differential Methylation throughout the Placental Genome:
      Epigenome-Wide Association Study of Two U.S. Birth Cohorts.
AB  - BACKGROUND: Cadmium (Cd) is a ubiquitous environmental toxicant that can
      accumulate in the placenta during pregnancy, where it may impair placental
      function and affect fetal development. OBJECTIVES: We aimed to investigate Cd
      associated variations in placental DNA methylation (DNAM) and associations with
      gene expression; we also aimed to identify novel pathways involved in Cd
      associated reproductive toxicity. METHODS: Using placental DNAM and Cd
      concentrations in the New Hampshire Birth Cohort Study (NHBCS, n=343) and the
      Rhode Island Child Health Study (RICHS, n=141), we performed an epigenome-wide
      association study (EWAS) between Cd and DNAM, adjusting for tissue heterogeneity
      using a reference-free method. Cohort-specific results were aggregated via
      inverse variance weighted fixed effects meta-analysis, and variably methylated
      CpGs were associated with gene expression. We then performed functional
      enrichment analysis and tests for associations between gene expression and birth
      size metrics. RESULTS: We identified 17 Cd-associated differentially methylated
      CpG sites with meta-analysis p-values<1*10-5, two of which were within a 5% false
      discovery rate (FDR). DNAM levels at 9 of the 17 loci were associated with
      increased expression of 6 genes (5% FDR): TNFAIP2, EXOC3L4, GAS7, SREBF1, ACOT7,
      and RORA. Higher placental expression of TNFAIP2 and ACOT7 and lower expression
      of RORA were associated with lower birth weight z-scores (p-values<0.05).
      CONCLUSION: Cd-associated differential DNAM and corresponding DNAM-expression
      associations were observed at loci involved in inflammatory signaling and cell
      growth. The expression levels of genes involved in inflammatory signaling
      (TNFAIP2, ACOT7, and RORA) were also associated with birth weight, suggesting a
      role for inflammatory processes in Cd-associated reproductive toxicity.
      https://doi.org/10.1289/EHP2192.

PMID- 29373863
TI  - Mutagenicity and Lung Toxicity of Smoldering vs. Flaming Emissions from Various
      Biomass Fuels: Implications for Health Effects from Wildland Fires.
AB  - BACKGROUND: The increasing size and frequency of wildland fires are leading to
      greater potential for cardiopulmonary disease and cancer in exposed populations;
      however, little is known about how the types of fuel and combustion phases affect
      these adverse outcomes. OBJECTIVES: We evaluated the mutagenicity and lung
      toxicity of particulate matter (PM) from flaming vs. smoldering phases of five
      biomass fuels, and compared results by equal mass or emission factors (EFs)
      derived from amount of fuel consumed. METHODS: A quartz-tube furnace coupled to a
      multistage cryotrap was employed to collect smoke condensate from flaming and
      smoldering combustion of red oak, peat, pine needles, pine, and eucalyptus.
      Samples were analyzed chemically and assessed for acute lung toxicity in mice and
      mutagenicity in Salmonella. RESULTS: The average combustion efficiency was 73 and
      98% for the smoldering and flaming phases, respectively. On an equal mass basis,
      PM from eucalyptus and peat burned under flaming conditions induced significant
      lung toxicity potencies (neutrophil/mass of PM) compared to smoldering PM,
      whereas high levels of mutagenicity potencies were observed for flaming pine and
      peat PM compared to smoldering PM. When effects were adjusted for EF, the
      smoldering eucalyptus PM had the highest lung toxicity EF (neutrophil/mass of
      fuel burned), whereas smoldering pine and pine needles had the highest
      mutagenicity EF. These latter values were approximately 5, 10, and 30 times
      greater than those reported for open burning of agricultural plastic, woodburning
      cookstoves, and some municipal waste combustors, respectively. CONCLUSIONS: PM
      from different fuels and combustion phases have appreciable differences in lung
      toxic and mutagenic potency, and on a mass basis, flaming samples are more
      active, whereas smoldering samples have greater effect when EFs are taken into
      account. Knowledge of the differential toxicity of biomass emissions will
      contribute to more accurate hazard assessment of biomass smoke exposures.
      https://doi.org/10.1289/EHP2200.

PMID- 29373865
TI  - The ATAD2 bromodomain binds different acetylation marks on the histone H4 in
      similar fuzzy complexes.

PMID- 29373864
TI  - Sulfur denitrosylation by an engineered Trx-like DsbG enzyme identifies
      nucleophilic cysteine hydrogen bonds as key functional determinant.

PMID- 29373866
TI  - An intermediate cell state allows rerouting of cell fate.
AB  - Somatic cell reprogramming into pluripotent stem cells using transcriptional
      factors or chemical compounds has been shown to include an intermediate cell
      state with epithelial features. Two recent papers show that this intermediate
      state can be redirected to create other differentiated cell types-specifically
      hepatocytes and neurons-using chemical cocktails. These results shed new light on
      a critical intermediate in cell fate conversion with mechanistic and practical
      implications.

PMID- 29373862
TI  - Association of Low-Moderate Arsenic Exposure and Arsenic Metabolism with Incident
      Diabetes and Insulin Resistance in the Strong Heart Family Study.
AB  - BACKGROUND: High arsenic exposure has been related to diabetes, but at low
      moderate levels the evidence is mixed. Arsenic metabolism, which is partly
      genetically controlled and may rely on certain B vitamins, plays a role in
      arsenic toxicity. OBJECTIVE: We evaluated the prospective association of arsenic
      exposure and metabolism with type 2 diabetes and insulin resistance. METHODS: We
      included 1,838 American Indian men and women free of diabetes (median age, 36 y).
      Arsenic exposure was assessed as the sum of inorganic arsenic (iAs),
      monomethylarsonate (MMA), and dimethylarsinate (DMA) urine concentrations
      (SigmaAs). Arsenic metabolism was evaluated by the proportions of iAs, MMA, and
      DMA over their sum (iAs%, MMA%, and DMA%). Homeostasis model assessment for
      insulin resistance (HOMA2-IR) was measured at baseline and follow-up visits.
      Incident diabetes was evaluated at follow-up. RESULTS: Median SigmaAs, iAs%,
      MMA%, and DMA% was 4.4 MUg/g creatinine, 9.5%, 14.4%, and 75.6%, respectively.
      Over 10,327 person-years of follow-up, 252 participants developed diabetes.
      Median HOMA2-IR at baseline was 1.5. The fully adjusted hazard ratio [95%
      confidence interval (CI)] for incident diabetes per an interquartile range
      increase in SigmaAs was 1.57 (95% CI: 1.18, 2.08) in participants without
      prediabetes at baseline. Arsenic metabolism was not associated with incident
      diabetes. SigmaAs was positively associated with HOMA2-IR at baseline but
      negatively with HOMA2-IR at follow-up. Increased MMA% was associated with lower
      HOMA2-IR when either iAs% or DMA% decreased. The association of arsenic
      metabolism with HOMA2-IR differed by B-vitamin intake and AS3MT genetics
      variants. CONCLUSIONS: Among participants without baseline prediabetes, arsenic
      exposure was associated with incident diabetes. Low MMA% was cross-sectional and
      prospectively associated with higher HOMA2-IR. Research is needed to confirm
      possible interactions of arsenic metabolism with B vitamins and AS3MT variants on
      diabetes risk. https://doi.org/10.1289/EHP2566.

PMID- 29373867
TI  - [Dacryoendoscopic Surgery-Factors Influencing Postoperative Results].
AB  - BACKGROUND: Dacryoendoscopy (DE) is an established method in lacrimal surgery.
      Long-term follow-up-analyses of this surgery are of great interest. Here, factors
      influencing postoperative success rates should be considered to elect suitable
      patients. METHODS: In this retrospective study, patients having had
      dacryoendoscopic surgery were included. Using a questionnaire, a prospective
      follow-up analysis was made. Pre- and intraoperative factors were correlated with
      treatment success, which was defined as improved epiphora, absence of a second
      lacrimal surgery and no signs of chronic dacryocystitis (secretion, pain at the
      lacrimal sac). Additionally, we asked for patient's satisfaction with the
      postoperative result (categorized in "very good", "good", "poor", and "bad").
      RESULTS: Overall, 215 DE of 182 patients (130 women, 52 men) were studied. Mean
      patient age was 58 +/- 17 years (range: 18 to 91 years). Follow-up was 31 to 77
      months (median: 55 months). Treatment success after this time was 59.1%, in which
      neither patient's age nor sex showed significant influences. In comparison to
      complete stenosis, incomplete obstruction could be treated successfully twice as
      often (p = 0.02). Patients suffering from ectatic lacrimal sacs had a risk of 1.9
      for failing therapy (p = 0.01). A trend concerning worse cure rates could be
      observed in patients with postsaccal localization of stenosis (p = 0.2) and an
      age of older than 49 years (p = 0.1). Surgical results evaluated by the patients
      were "very good" in 32.1% and "good" in 30.2%. CONCLUSION: Dacryoendoscopy with
      its minimally invasive approach is suitable as a first-step procedure in lacrimal
      surgery. The absence of a scar and the quick recovery are vitally important for
      the patients. Medically important is that the topographic anatomy is preserved by
      using dacryoendoscopy, so other surgical techniques can be performed later
      without limitations, if necessary. Patients with incomplete obstructions and a
      localization of stenosis, being pre- to intrasaccal, profit from this treatment
      method in particular.

PMID- 29373868
TI  - [Chronic Progressive External Ophthalmoplegia Ptosis: Problems with Diagnostics
      and Treatment].
AB  - Ptosis is often the first symptom of chronic progressive external ophthalmoplegia
      (CPEO), a rare muscle disorder. As the disease progresses, it can lead to ocular
      motility defects. Ptosis is present in the early stages of the disease and can be
      corrected by levator surgery. Due to the rarity of CPEO (< 1% of ptosis
      patients), further diagnostic steps with muscle biopsy and genetic analysis of
      mitochondrial DNA are usually not considered in the early phase. Intraoperative
      abnormal observations during ptosis surgery and postoperative motility problems
      are signs of CPEO. If CPEO is confirmed, alternative surgical methods can correct
      the ptosis, like frontalis suspension.

PMID- 29373869
TI  - [Tarsal Kink: Pathognomonic Presentation and Therapy of a Rare Congenital Upper
      Eyelid Malformation].
AB  - BACKGROUND: Presentation of a congenital abnormality that is rare, but follows a
      distinct course and can be diagnosed and cured promptly if the pathognomonic
      presentation is recognized. A congenital tarsal kink leads to a malposition of
      the upper eyelid margin that must not be missed, as it will lead to ulcerative
      keratitis if it is not treated. CASE PRESENTATION: An otherwise healthy newborn
      was presented after delivery with forceps with marked unilateral purulent
      secretion and blepharospasm. DIFFERENTIAL DIAGNOSIS: Neonatal dacryocystitis,
      gonococcal infection, congenital entropion with ulcerative keratitis, tarsal
      kink. EXAMINATION: It was not possible to fully examine the lid and cornea with
      the baby awake. Due to total inversion of the lid margin, no lashes could be
      seen. Under general anesthesia, the tarsal kink, with complete inversion of the
      lid margin and a corneal ulcer, was confirmed. TREATMENT: The literature offers
      several methods to correct this rare malposition, all of which aim to strengthen
      the anterior lamella to correct the kink. After incision of the kink and
      repositioning of the tarsus and securing the position with fixation sutures, the
      ulcer healed quickly and completely; lid closure and lid contour were normal and
      symmetrical. SUMMARY: Complete inversion of the lid margin is the pathognomonic
      sign of tarsal kink, giving the impression of "missing" lashes, accompanied by
      blepharospasm, followed by purulent secretion and corneal ulceration. The
      condition must not be misdiagnosed as only immediate correction can prevent
      severe damage.

PMID- 29373870
TI  - ?

PMID- 29373871
TI  - [DOG and BVA Guideline No. 24b - Noninfectious uveitis posterior].

PMID- 29373872
TI  - Depression in Women with Breast Cancer: A Systematic Review of Cross-Sectional
      Studies in Iran
AB  - Objective: Breast cancer is one of the most common cancers in women and has more
      severe mental and emotionaleffects than other types. Depression as a mental
      disorder affects people's mental well-being, physical symptoms,occupational
      performance, and finally quality of life. The aim of this study was to determine
      depression levels inIranian women with breast cancer. Methods: A systematic
      review study was conducted in 2017. English and Persiandatabases (PubMed, SCOPUS,
      Web of Science, Google Scholar, SID, Magiran) were searched with key words suchas
      Depression Or Depressive Disorders AND Women AND Breast Cancer OR Tumor OR
      Neoplasm OR MalignancyAND Iran. Inclusion criteria allowed for cross-sectional
      studies conducted in Iran (published in English or Persianlanguage journals),
      studies that had key words in their keywords or their titles and standard
      instruments for measuringdepression in patients. Of the 160 publications found,
      eight were selected after reviewing the title, abstract and fullarticle. Results:
      Age of women with breast cancer in selected studies ranged from 43.8 (SD = 47.1)
      to 55.9 (SD = 14.6)years. Duration of cancer in most studies was about 1-2 years.
      In most studies, mild levels of depression for womenwith breast cancer were
      present. However, in one study it was stated that 69.4% of participants had
      serious levels ofdepression. Conclusions: There is increase in the risk of
      depression in women with breast cancer. Therefore, it seemsnecessary to plan
      preventive and therapeutic measures in order to improve the mental health and
      quality of life of theaffected patients.

PMID- 29373873
TI  - Attitude and Practice Regarding Breast Cancer Early Detection among Iranian
      Women: A Systematic Review
AB  - Objectives: To determining attitudes and practice regarding breast cancer early
      detection techniques (breastself-examination (BSE), clinical breast examination
      (CBE) and mammography) among Iranian woman. Methods:International (PubMed, ISI,
      and Google Scholar) and national (SID and Magiran) databases were reviewed up
      toSeptember 2017 to identify articles related to the attitudes and practices of
      Iranian women concerning breast cancerscreening behavior with reference to BSE ,
      CBE and mammography. The screening steps, analysis of quality of thestudies and
      extraction of the papers were performed by two reviewers. Results: Of the 532
      studies included initially, 21performed on 10,521 people were considered
      eligible. Subjects with a positive attitude toward BSE in various studieswere
      13.5% to 94.0% with an average of 47.6%. Positive attitudes to CBE and
      mammography were found in 21.0%and 26.4%, respectively. Participant performance
      of BSE ranged from 2.6% to 84.7%, with an average of 21.9%. Therespective figures
      for CBE and mammography were 15.8% and 16.7%. Conclusion: Considering the poor
      performanceand low rates for positive attitudes, it is suggested that educational
      programs should be conducted across the country.

PMID- 29373874
TI  - More Reasonable Animal Model for Study the Effect of Pneumoperitoneum on
      Abdominal Tumor Cells
AB  - Background: Many animal experimental studies showed that abdominal tumor cells
      will be widely spread duringlaparoscopic treatment and grow into metastases.
      These results are different from clinical observations. There is ahypothesis that
      too much tumor cells was injected in the animals lead to the results of theses
      bias. We aim to learn thedifference of abdominal cavity volume between human body
      and the nude mice and to determine reasonable amountof tumor cells in the animal
      experiments. Methods: The insufflated CO2 volume which represents the capacity of
      theabdominal cavity was recorded during laparoscopic process in 212 patients and
      20 nude mice respectively, the relativevolume of nude mice and human body was
      calculated.Based on data from the literature and this study , the amountof tumor
      cells in the animal experiments was determined.According to these data, we set up
      a new animal modeland a traditional one respectively,and compared the rate of
      successful modeling and tumor formation between twoanimal models. Results: The
      intraperitoneal volumes of humans and nude mice were 3.01+/-0.36 L and 0.011+/
      0.001 Lrespectively.The number of tumor cells that be uesd in animal should be
      approximately 0.26*105 in terms of knowndata in human beings.Compared with the
      traditional animal model which formed a large number of intraperitonealtumor
      metastasis, the new animal model was shows more moderately,and the rate of
      successful modeling was similar.Conclusion: In animal experiments, to simulate
      the clinical situation, about 0.26*105 tumor cells should be inject inperitoneal
      cavity of the nude mice.

PMID- 29373875
TI  - The Economic Burden of Metastatic Castration Resistant Prostate Cancer and
      Skeletal Related Events in Japanese University Hospitals
AB  - Objective: Although androgen deprivation therapy (ADT) has improved the survival
      and quality of life of patientswith prostate cancer, resistance to treatment
      inevitably results in transition to a castration resistant state (CRPC) and,
      inadvanced cases, bone metastasis, leading to skeletal related events (SRE). In
      order to understand the current burden onpatients in Japan, there is a need to
      estimate the healthcare costs of CRPC treatment in current clinical practice.
      Methods:This retrospective observational cohort study utilized claims data from
      13 national university hospitals through thePlatform for Clinical Information
      Statistical Analysis database. Extracted data included the use of diagnostic
      tests, thefrequency and cost of hospitalizations and outpatient visits, and
      medication costs, using values from the Healthcare FeeSystem and the National
      Health Insurance Drug Price List relative to each observed year. Results: Data
      were collectedfrom 4001 patients with CRPC, 97% of whom had undergone ADT.
      Between 2005 and 2016, the mean annualizeddirect medical cost per patient was
      Y739,147 (US$7060), of which 91% was related to medication, 4.8% to laboratoryand
      imaging, 4.1% to radiotherapy, and 0.1% to surgery. A total of 771 (19%) of the
      4001 CRPC patients experiencedan SRE. Resource utilization was significantly
      higher (p<0.0001) in patients with SRE than in those without, withmean annualized
      medication costs per patient of Y1,074,885 and Y659,006, respectively, and
      Y108,807 and Y71,392,respectively, for laboratory and imaging. The occurrence of
      even one SRE led to a significant increase in costs and theuse of analgesics,
      compared to the prior period. Conclusions: A diagnosis of CRPC is associated with
      considerablehealthcare resource utilization and increased economic burden on
      patients, which are significantly higher in those withSREs. Treatments that can
      prevent or delay SREs may help ease this burden, thereby providing cost savings
      acrossJapanese healthcare systems.

PMID- 29373876
TI  - Prognostic Value of IL-10 and Its Relationship with Disease Stage in Iranian
      Patients with Multiple Myeloma
AB  - Background: Several studies have demonstrated roles of interleukins in the
      pathogenesis of multiple myeloma (MM).Objective: Here we considered correlations
      among serum levels of IL-10, stage of disease and clinical laboratory
      diseasemarkers in Iranian MM patients to investigate whether the interleukin
      might have prognostic significance. Materialsand Methods: In this cross-sectional
      study, a total of 60 subjects (40 patients and 20 controls) were recruited.
      Afterpreliminary laboratory tests, disease stage was evaluated and serum levels
      of IL-10 were measured using an enzymelinkedimmunosorbent assay (ELISA). Results:
      The mean concentration of serum IL-10 in patients (2.39+/-0.82 ng/ml) was
      significantly higher (p<0.0001) than that in healthy controls (0.34+/-0.15
      ng/ml). A positive and significantcorrelation (p<0.0001) was observed with the
      disease stage. The highest plasma cell proportions were recorded forMM stage III
      patients (68.8+/-9.21%), differing significantly from those of stage I patients
      (50.0+/-10.0%; p=0.011). TheBeta-2 microglobulin value in stage III patients
      (7.7+/-1.13mg/l) was significantly higher than in those with stage II(4.31+/-0.64
      mg/l; p<0.0001) and stage I (2.8+/-0.4 mg/l; p<0.0001). There was also a positive
      and significant correlation(p=0.002) between IL-10 levels and B2M. A trend
      (p=0.06) for positive correlation was observed between IL-10 levelsand plasma
      cells. Conclusions: The correlation of IL-10 with disease stage and markers of
      disease activity indicatesimportant roles in MM pathogenesis and progression.
      Therefore, measurement of serum IL-10 might be helpful forpredicting stage and
      clinical management of MM.

PMID- 29373878
TI  - Brain-Derived Neurotrophic Factor Role in Autism Remains Elusive: A Flashback on
      the Route That Has Brought Us Here.

PMID- 29373877
TI  - Serum MicroRNA-21 Negatively Relates to Expression of Programmed Cell Death-4 in
      Patients with Epithelial Ovarian Cancer
AB  - Background: Ovarian cancer is the third most common cancer of the female genital
      tract and the leading causeof cancer death associated with gynecologic tumors.
      MicroRNAs regulate at least 60% of human genes, includingtumor suppressor genes
      and oncogenes and, thereby, can affect cancer risk. Aim of the work: We aimed to
      assess anydiagnostic role for serum miR-21 as a biomarker in human ovarian cancer
      and to study relations with programmedcell death-4 (PDCD4), one of its target
      proteins, hoping to help explain heterogeneity of this cancer type and
      facilitatestratification of regimens for therapy. Subjects and Methods: A total
      of 60 newly diagnosed ovarian cancer cases and30 apparently healthy females were
      recruited. Serum microRNA-21 levels were measured by TaqMan- Real time PCRassay
      and PDCD4 by ELISA. Results: Significant over-expression of serum miR-21 and
      lower serum PDCD4 levelswere observed in ovarian cancer patients as compared to
      the control group. A statistically significant inverse correlationwas also
      evident between miR-21 and PDCD4. However, no significant links were noted
      observed between miR-21and tumor grade, stage or histopathological type.
      Conclusion: The present work showed significantly up-regulationof serum miR21 in
      the recruited group of patients and a significant inverse relation association
      between miR-21andPDCD4. These findings suggest that miR-21 may be used as a
      diagnostic biomarker for human ovarian cancer.

PMID- 29373879
TI  - Ghrelin Alleviates MDMA-Induced Disturbance of Serum Glucose and Lipids Levels in
      the Rat.
AB  - Hepatotoxicity is one of the clinically adverse effects of ecstasy (3, 4
      methylenedioxymethamphetamine; MDMA) consumption. The detoxification tissue,
      liver, plays a central role in maintaining circulating levels of glucose and
      lipid. Hypoglycemia and hypotriglyceridemia have been reported due to ecstasy
      abuse. Ghrelin is a 28-amino-acid peptide secreted predominantly from the
      stomach. It has been demonstrated that ghrelin has hepatoprotective effects and
      is able to increase blood glucose concentration. In the current study, we
      explored the effect of hepatotoxic dose of MDMA and therapeutic use of exogenous
      ghrelin on the serum levels of glucose and lipids in four groups of rats. MDMA
      caused a severe and transient reduction in circulating levels of glucose and
      triglyceride and increased serum LDL. However, cholesterol and HDL levels
      remained unchanged. Meanwhile, altered hepatic architecture was observed with
      intracellular vacuolation that may indicate intracellular accumulation of lipid
      droplets. In addition, following ghrelin administration, the blood sugar levels
      improved and LDL levels returned to the baseline value, and ghrelin treatment did
      not improve triglycerides levels. These results showed that MDMA causes
      hypoglycemia, hypotriglyceridemia, and hyper LDL-cholesterolemia. To our
      knowledge, this is the first report showing ghrelin administration could improve
      hypoglycemia and normalize LDL levels induced by MDMA and partially restore
      hepatic architecture.

PMID- 29373880
TI  - The Effect of Recombinant HopH Protein of Helicobacter pylori on the VEGF
      Expression in Metastatic Breast Cancer Model.
AB  - Breast cancer imposes a considerable amount of cancer-related mortality and
      morbidity among women worldwide. Many efforts are in progress to reduce the
      disease burden and amongst the bacterial-based products received considerable
      attention as potential anti-cancer drugs. In the present study, the effect of
      recombinant pro-inflammatory outer membrane protein (HopH) of Helicobacter pylori
      on the angiogenic factor and tumor development in metastatic breast cancer model
      was evaluated. The HopH gene was cloned into Pet28a vector, induced by IPTG and
      expressed and purified by Ni-NTA affinity chromatography. The expressed protein
      was confirmed by SDS-page. The breast cancer tumor induction was performed using
      Breast cancer cell line (4T1). The mice were divided into different groups and
      underwent treatment by recombinant HopH and Herceptin, subsequently. The
      treatment effectiveness on tumor size was followed, and the expression level of
      vascular endothelial growth factor was evaluation by real time PCR. The SDS-PAGE
      analysis confirmed the expression of HopH protein with an approximate 34KD
      weight. Based on our results, the expression level of VEGF was significantly
      reduced in HopH-treated mice group comparing to the control and Herceptin group.
      Our results have shown that the recombinant HopH protein can effectively reduce
      VEGF expression in breast cancer tumor which was associated with reduction of
      tumor size. The HopH protein can be considered as a potential anti-cancer agent
      for future cancer therapeutic studies.

PMID- 29373881
TI  - The Impact of Thymidylate Synthase and Methylenetetrahydrofolate Reductase
      Genotypes on Sensitivity to 5-Fluorouracil Treatment in Colorectal Cancer Cells.
AB  - 5-fluorouracil (5-FU) is one of the major components of many standard regimens
      for chemotherapy of colorectal cancer (CRC) and some other malignancies. Given
      the known relationship between thymidylate synthase (TS) and
      methylenetetrahydrofolate reductase (MTHFR) activity and 5-FU metabolism, this
      study investigated the impact of selected functional polymorphisms of the TS and
      MTHFR genes on chemotherapy resistance in 5 human CRC cell lines. HCT116, SW1116,
      HT29/219, LS180, and Caco-2 CRC cells were cultured as monolayer and their
      chemosensitivity to 5-FU, oxaliplatin, and irinotecan was determined by MTT
      assay. Genomic DNA was extracted from the cultured cells, and a 6-bp insertion or
      deletion (6-bp ins/del) polymorphism in 3'-UTR of the TS gene was determined by
      the PCR-RFLP method. Genotyping of MTHFR 677 C/T and 1298A/C single nucleotide
      polymorphism (SNP) was also performed by MS-PCR and PCR-RFLP, respectively. Caco
      2 with the homozygous TS 6-bp ins/ins and MTHFR 677 T/T and 1298 C/C genotype,
      was the most 5-FU resistant cell line. HCT116 with the homozygous TS 6-bp del/del
      and MTHFR 1298 A/A and heterozygous MTHFR 677 C/T genotype was the least 5-FU
      resistant cell. LS180, the second most 5-FU resistant cell line, was heterozygous
      for all three polymorphic sits. HT29/219 and SW1116 cells with homozygous TS 6-bp
      ins/ins and heterozygous MTHFR 677 C/T and 1298 A/C genotypes had intermediate 5
      FU sensitivity. The results indicate that TS 3'-UTR 6-bp insertion and MTHFR 677T
      and 1298C alleles increase 5-FU resistance in CRC cells. No relationship was
      observed between TS and MTHFR genotypes and oxaliplatin or irinotecan sensitivity
      in these cells.

PMID- 29373882
TI  - The Association Between Bisphenol A and Polycystic Ovarian Syndrome: A Case
      Control Study.
AB  - Polycystic ovarian syndrome (PCOS) is an endocrine metabolic disorder with
      unclear etiopathogenesis among reproductive age women. Evidences show genetic
      susceptibility and environmental factors were associated with PCOS. The aim of
      this study was to find the association between urinary concentrations of
      Bisphenol-A as an endocrine disrupting chemical (EDC) and PCOS. A case-control
      study was conducted in 51 samples in each group. All cases were selected from
      women who diagnosed with PCOS at Gynecology and infertility center. The control
      group was selected from women who had clinical file in the center due to previous
      problem and came for routine check-up and pap smear. The participants were asked
      to collect a first-morning urine sample before any medical interventions. Total
      BPA in urine were measured with High Performance Liquid Chromatography (HPLC)
      method. Comparison of BPA level between two groups shows significantly higher
      level in PCOS group compared with control group (3.34 +/- 2.63 vs 1.43 +/- 1.57
      ng/mL, P<0.001). Using logistic regression analysis, BPA as the main dependent
      variable, was significantly associated with PCOS with adjusted Odds Ratio (OR)
      equal to 1.53 (95% CI: 1.14-2.05, P =0.004). The results of this study indicated
      that BPA may play a major role in the PCOS pathogenesis. Further investigations
      with better design are necessary to confirm this association.

PMID- 29373883
TI  - The Relation of Carotid Arteries' Intima-Media Thickness With Snoring and
      Obstructive Sleep Apnea in Type 2 Diabetes Patients.
AB  - In recent decades, the relation of carotid artery intima-media thickness (IMT) as
      a marker of atherosclerosis with snoring and sleep disorders has been drawing
      attention. The aim of this study was to evaluate the relation of carotid arteries
      IMT with snoring in type 2 diabetic patients. This cross-sectional study was
      performed on type 2 diabetes patients referring to Mashhad University of Medical
      Sciences' clinics. The stop Bang, Epworth sleepiness scale, and Stanford
      questionnaires were used for evaluation of daily sleepiness and snoring. For
      assessment of carotid artery thickness, Madison X8 ultrasound with 10 MHz
      superficial probes was utilized. The data were entered into SPSS software, and
      then the ANOVA test with Turkey, chi-square comparison technique, and Kruskal
      Wallis with Mann-Whitney U technique was used. The level of significance was
      considered P<=0.05. In total 80 patients (37 snorers and 43 non-snorers) entered
      the study. The mean carotid artery IMT in the group of snoring patients (0.72+/
      0.17) was significantly higher than non-snorers (0.56+/-0.17) (P<0.001).
      Frequency of daily based on Stanford and ESS questionnaires was 23.8% and 39.2%.
      The association of sleepiness and snoring was confirmed by Stanford and ESS
      questionnaires with P=0.026 and P=0.007. Patients with higher risk of apnea had
      higher thickness of the mean carotid artery IMT (P<0.001). The mean carotid
      artery IMT had a positive significant relation with age (P=0.002), serum
      creatinine level (P<0.002), blood cholesterol (P=0.02) and HbAIC level (P=0.04).
      Findings of this study provides evidence on the relation of carotid artery IMT in
      diabetic patients with snoring independent of other effective factors. Also,
      results showed that snoring is associated with increased daily sleepiness and
      patients with higher risk of apnea had higher thickness of the mean carotid
      artery IMT.

PMID- 29373884
TI  - Effect of Progesterone on Latent Phase Prolongation in Patients With Preterm
      Premature Rupture of Membranes.
AB  - Preterm premature rupture of membranes (PPROM) is a condition leading to an
      increased risk of maternal and neonatal morbidity and mortality in pregnant
      women. To prevent this complication, some studies have proposed using
      prophylactic progesterone. However, due to lack of sufficient relevant data,
      there is still need for further studies in this regard. This study was performed
      to determine the effect of rectal progesterone on the latent phase and maternal
      and neonatal outcome variables in females with PPROM. During the present
      randomized clinical trial study (IRCT201512077676N4), a total of 120 patients
      with PPROM at pregnancy ages between 26 and 32 weeks were randomly assigned to 2
      equal intervention and control groups. In the intervention group, progesterone
      suppositories (400 mg per night) were administered until delivery or completion
      of the 34th gestational week and was compared with placebo effect in control
      group. The latent phase and maternal and neonatal outcome variables were compared
      between the two groups. The mean age of patients was 29.56+/-5.66 (19-42) and
      29.88+/-5.57 (17-40) years in the intervention and control group, respectively.
      The two groups were almost identical in the confounding factors. The median
      latent phase was 8.5 days in the intervention group vs. 5 days in the control
      group in the 28th-30th weeks of gestation, which was significantly higher in the
      intervention group (P=0.001). Among maternal and neonatal outcome variables, only
      the mean birth-weight was significantly higher in the intervention group than
      that in the controls (1609.92+/-417.28 gr vs. 1452.03+/-342.35 gr, P=0.03).
      Administration of progesterone suppository in patients with PPROM at gestational
      ages of 28 to 30 weeks is effective in elongating the latent phase and increasing
      birth-weight with no significant complications.

PMID- 29373885
TI  - The Effect of Rosa Damascena Extract on Expression of Neurotrophic Factors in the
      CA1 Neurons of Adult Rat Hippocampus Following Ischemia.
AB  - Ischemic stroke is an important cause of death and disability in the world. Brain
      ischemia causes damage to brain cell, and among brain neurons, pyramidal neurons
      of the hippocampal CA1 region are more susceptive to ischemic injury. Recent
      findings suggest that neurotrophic factors protect against ischemic cell death. A
      dietary component of Rosa damascene extract possibly is associated with
      expression of neurotrophic factors mRNA following ischemia, so it can have
      therapeutic effect on cerebral ischemia. The present study attempts to evaluate
      the neuroprotective effect of Rosa damascene extract on adult rat hippocampal
      neurons following ischemic brain injury. Forty-eight adult male Wistar rats
      (weighing 250+/-20 gr and ages 10-12 weeks) used in this study, animals randomly
      were divided into 6 groups including Control, ischemia/ reperfusion (IR), vehicle
      and three treated groups (IR+0.5, 1, 2 mg/ml extract). Global ischemia was
      induced by bilateral common carotid arteries occlusion for 20 minutes. The
      treatment was done by different doses of Rosa damascena extract for 30 days.
      After 30 days cell death and gene expression in neurons of the CA1 region of the
      hippocampus were evaluated by Nissl staining and real time PCR assay. We found a
      significant decrease in NGF, BDNF and NT3 mRNA expression in neurons of CA1
      region of the hippocampus in ischemia group compared to control group (P<0.0001).
      Our results also revealed that the number of dark neurons significantly increases
      in ischemia group compared to control group (P<0.0001). Following treatment with
      Rosa damascene extract reduced the number of dark neurons that was associated
      with NGF, NT3, and BDNF mRNA expression. All doses level had positive effects,
      but the most effective dose of Rosa damascena extract was 1 mg/ml. Our results
      suggest that neuroprotective activity of Rosa damascena can enhance hippocampal
      CA1 neuronal survival after global ischemia.

PMID- 29373886
TI  - The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor
      Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF.
AB  - Cerebral ischemic stroke is a common leading cause of disability. Flaxseed is a
      richest plant-based source of antioxidants. In this study, the effects of
      flaxseed oil (FSO) pretreatment on functional motor recovery and gene expression
      and protein content of neurotrophic factors in motor cortex area in rat model of
      brain ischemia/reperfusion (I/R) were assessed. Transient middle cerebral artery
      occlusion (tMCAo) in rats was used as model brain I/R. Rats (6 in each group)
      were randomly divided into four groups of Control (Co+normal saline [NS]), Sham
      (Sh+NS), tMCAo+NS and tMCAo+FSO. After three weeks of pretreatment with vehicle
      or FSO (0.2 ml~800 mg/kg body weight), the rats were operated in sham and
      ischemic groups. Ischemia was induced for 1 h and then reperfused. After 24 h of
      reperfusion, neurological examination was performed, and animals were sacrificed,
      and their brains were used for molecular and histopathological studies. FSO
      significantly improved the functional motor recovery compared with tMCAo+NS group
      (P<0.05). A significant reduction in brain-derived neurotrophic factor (BDNF) and
      glial cell-derived neurotrophic factor (GDNF) mRNAs and protein levels were
      observed in the tMCAo+NS group compared with Co+NS and Sh+NS group (P<0.05). A
      significant increase of BDNF and GDNF mRNAs and proteins was recorded in the
      tMCAo+FSO group compared with Co+NS, Sh+NS and tMCAO+NS groups (P<0.05). The
      results of the current study demonstrated that pretreatment with FSO had
      neuroprotective effects on motor cortex area following cerebral ischemic stroke
      by increasing the neurotrophic factors (BDNF, GDNF).

PMID- 29373887
TI  - Chondrosarcoma in Metachondromatosis: A Rare Case Report.
AB  - Metachondromatosis which was first described in 1971 by Maroteaux is a rare
      genetic disease consisting of osteochondromas and enchondromas, caused by loss of
      function of the PTPN11 gene. It is distinct from other cartilaginous tumors such
      as multiple osteochondromas and hereditary multiple exostosis by the distribution
      and orientation of lesions, and pattern of inheritance. In Metachondromatosis
      osteochondromas typically occur in hands, feet, femur, and tibia while
      enchondromas commonly affect the pelvic bones and femurs. Both tumors are
      generally reported to regress in adulthood. To the best of our knowledge only one
      case of Chondrosarcoma has been reported, and our case is the second reported
      case of Chondrosarcoma in metachondromatosis.

PMID- 29373888
TI  - Sarcoid Myopathy Mimicking Polymyositis: A Case Report and Pool Analysis of the
      Literature Reviews.
AB  - A 59-year-old man presented with proximal myopathy, myalgia, and weight loss,
      with the initial markedly elevated serum creatine kinase at 11,000 U/L. Due to
      his refusal for muscle biopsy, he was initially treated as inflammatory myositis
      and responded well with the corticosteroids. However, he subsequently had a
      relapse of the symptoms with more extensive systemic involvement, i.e.,
      hypercalcemia, lymphadenopathy and subcutaneous nodules. Finally, a biopsy of the
      thigh and subcutaneous nodule revealed non-caseating granulomatous inflammation,
      consistent with sarcoidosis. He responded well to the corticosteroids, and
      finally, azathioprine was added as a steroid-sparing agent. Including our series,
      there are 103 cases of symptomatic muscle involvement in sarcoidosis patients
      published in the English literature to date. Further pool analysis of the cases
      will be reported in this review.

PMID- 29373889
TI  - Paraplegia After Off-Pump Coronary Artery By-Pass Grafting.
AB  - Paraplegia is an exceedingly rare neurologic complication after off-pump coronary
      artery bypass graft (OPCAB) surgery commonly caused by spinal cord ischemia
      (SCI). SCI is not a well unknown clinical phenomenon in the postoperative course.
      SCI has been reported after noncardiac surgery in otherwise healthy subjects in
      whom only one risks factor i.e. severe hypotension has been documented. SCI has
      also been reported as a rare complication among the other neurologic sequels of
      cardiac surgery. We report a case of paraplegia in a patient with metabolic
      syndrome and multiples risk factors after an OPCAB. This patient may be
      considered as an interesting case as no any ischemic event was found in the
      imaging modalities and culprit lesion may be attributed to 1-left internal
      thoracic artery use as an important blood perfusion to anterior spinal artery
      vasculature and 2-Disc herniation at intervertebral space of T as a culprit
      lesion 3-transient intraoperative hypotension. The patient was managed by lower
      extremities physiotherapy and skin care, however, after 3months of follow-up, no
      evidence of recovery was detected.

PMID- 29373890
TI  - Long-term Results of Adjuvant Imatinib Treatment for Localized Gastrointestinal
      Stromal Tumors after Surgery
AB  - Objective: Despite the development of two significant classifications for
      recurrence risk evaluation among patientsengaged with gastrointestinal stromal
      tumor and corresponding treatment criteria, recurrence happens in a numberof the
      patients who were once classified as ineligible for treatment and hence removed
      from treatment program. Assuch, the aim of the present study is to increase the
      number of patients recognized as eligible for treatment, so as tofurther reduce
      recurrence rate of this disease. Materials and Methods: A total of 26 patients
      from Ilam, Kermanshah,Lorestan, Kurdistan, and some parts of Hamedan, entered
      this study from 2006 until 2016. The western provincesincluded have similar
      socioeconomical conditions. Inclusion criteria were operable tumors confirmed
      radiologicallywith a gross size larger than 3 centimeters regardless of the
      mitosis rate in microscopic power fields, tumor location, orpresence of
      peritoneal involvement during the surgery. Imatinib capsules were administered
      daily at 400 mg for 3 years.The patients were followed up every 3 months by
      radiology, ultrasonography, biochemical assessment, and clinicalexamination.
      Results and Conclusions: The overall survival after 10-years follow up was 100%,
      while 5-year survivalwithout relapse was 95%. Mean overall survival was 106
      months, and only one patient who had limited peritonealinvolvement experienced
      relapse and he is still alive after 2 years. The drug was well tolerated and no
      significant sideeffects were observed.

PMID- 29373891
TI  - Fas-Antisense Long Noncoding RNA and Acute Myeloid Leukemia: Is There any
      Relation?
AB  - In recent years, lncRNAs have been considered as potential predictive biomarkers
      for prognosis of different humancancers. One example is the FAS antisense RNA 1
      (FAS-AS1) located in the 10q23.31 region which is transcribed fromthe opposite
      strand of the FAS gene. FAS has an important role in regulation of apoptotic
      pathways and there is aninverse correlation between FAS-AS1 expression level and
      production of the soluble form of Fas, so that it might havepotential as a
      therapeutic target to improve chemotherapy effectiveness. In the present study we
      therefore evaluatedFAS-AS1 expression in blood samples of de novo AML patients
      and healthy controls using real-time quantitativereverse transcription-PCR (qRT
      PCR). Our results indicated that the expression level of FAS-AS1 lncRNA
      demonstratedno significant difference between AML patients and healthy
      individuals. We conclude from the obtained data thatFAS-AS1 is not an informative
      and reliable biomarker for AML diagnosis, although our results need to be
      confirmedin further studies.

PMID- 29373892
TI  - Curcumin Analog Pentagamavunon-1 (PGV-1) Sensitizes Widr Cells to 5-Fluorouracil
      through Inhibition of NF-kappaB Activation
AB  - Cell cycle regulation and the NF-kappaB pathway in cancer cells are important in
      mediating resistance to 5-Fluorouracil(5-FU). Pentagamavunon-1 (PGV-1), a
      curcumin analog, is known to exhibit stronger growth inhibitory effects
      thancurcumin itself in several cancer cells. In this study, we evaluated the
      potency of PGV-1 in combination with 5-FUin WiDr colon cancer cells. In MTT
      assays, PGV-1 did not only exhibit stronger growth inhibitory effects than both5
      FU and curcumin, but also enhanced the cytotoxicity of 5-FU. Flow cytometry
      demonstrated that single treatmentswith PGV-1 and 5-FU resulted in different
      effects on cell cycle profiles. PGV-1 induced G2/M arrest while 5-FUcaused S
      phase arrest at low concentration (1 MUM) and G1-phase arrest at high
      concentration (100 MUM). Interestingly,the combination of 5-FU and PGV-1 enhanced
      cell accumulation in S-phase. Although a single treatment with either5-FU or PGV
      1 increased cyclin D1 at the protein level, the combination treatment resulted in
      significant suppression.In addition, PGV-1 inhibited activation of NF-kappaB and
      suppressed the expression of cyclooxygenase-2, an NF-kappaBdownstream protein. In
      conclusion, PGV-1 increased the cytotoxic effect of 5-FU on WiDr cells through
      inhibition ofNF-kappaB activation.

PMID- 29373893
TI  - The Effect of Mammary Extracellular Matrix in Controlling Oral and Mammary Cancer
      Cells
AB  - Extracellular matrix (ECM) plays an important role in the normal physiology of
      tissues and progression to disease.Earlier studies and our external microarray
      data analysis indicated that mammary matrix from involuting tissue
      showedupregulation of genes involved in ECM remodeling. The present study
      examines the fate of mammary and oral cancercells grown in the ECM from lactating
      mammary gland. Our findings show that non-tumorigenic cells, MCF10A andDOK cells
      did not proliferate but the tumorigenic and metastatic cells, SCC25 and MDA-MB
      231, underwent apoptosiswhen grown on mammary ECM isolated from lactating mice.
      In addition, the cytokinesis marker, CEP55, was repressedin the oral and breast
      cancer cells. In contrast, these cells proliferated normally on mammary ECM
      isolated from miceundergoing involution. External microarray data analysis of
      mammary tissue further revealed over expression (~16 fold)of QSOX1 gene, which
      promotes cellular quiescence, in lactating mammary gland. A recent study has
      indicated thatQSOX1 overexpression in breast cancer cells led to reduced
      proliferation and tumorigenic properties. This extracellularprotein in mammary
      ECM may be responsible for reduced cellular proliferation. The present study has
      shown that ECMfrom lactating mammary gland can regulate signals to oral and
      breast cancer cells to halt cell division. This preliminaryobservation provided
      insights into the potential role of ECM factors present in lactating mammary
      gland as therapeutictargets to control cancer cell division. This preliminary
      study is an attempt to understand not only the requirement ofECM remodeling
      factors essential for the growth and survival of cancer cells but also the
      factors present in the lactationmatrix that simultaneously halts cell division
      and selectively inhibits the growth of cancer cells.

PMID- 29373894
TI  - Health-Related Quality of Life before and after Surgical Resection of
      Hepatocellular Carcinoma: A Prospective Study
AB  - Background and Objectives: This large-scale prospective cohort study of a Taiwan
      population applied generalizedestimating equations (GEEs) to evaluate changing
      trends in health-related quality of life (HRQoL) and to comparepredictors of
      HRQoL before and after surgical resection of hepatocellular carcinoma (HCC)
      performed during2011-2014. Materials and Methods: The Short Form-36 Health Survey
      (SF-36) and Functional Assessment of CancerTherapy-Hepatobiliary were used in a
      preoperative assessment and in 3- and 6-month postoperative assessments of 332HCC
      patients. Results: The HRQoL was signficantly (p<0.05) improved at 3 months after
      surgical resection of HCCand plateaued at 6 months after surgery. Scores for both
      the SF-36 Physical Component Summary (PCS) and MentalComponent Summary (MCS) were
      significantly higher at the third month after surgery (p<0.05) compared to
      thepreoperative period. Both scores also exceeded the norms after hepatic
      resection of HCC. However, PCS scores weregenerally higher than MCS scores
      throughout the study period. After adjusting for time effects and baseline
      predictors,GEE approaches revealed the following explanatory variables for HRQoL:
      time of HRQoL assessment, gender, age,education, coresidence with family,
      chemotherapy, average length of hospital stay, and preoperative functional
      status.Conclusions: Hepatic resection significantly increased HRQoL in patients
      with HCC (p<0.05). However, an evaluationof HRQoL after hepatic resection should
      consider several factors other than outcomes of the surgery itself.
      Additionally,patients should be advised that their HRQoL improvement after
      surgery might depend not only on the success of surgery,but also on their
      preoperative functional status.

PMID- 29373895
TI  - Pattern of Failure with Locally Advanced Cervical Cancer- A Retrospective Audit
      and Analysis of Contributory Factors
AB  - Background: The majority of the global burden of cervical cancer is affecting
      developing countries. Despiteimprovement in treatment of patients presenting at a
      locally advanced stage, approximately 50% experience recurrencewithin the 1st two
      years. This study was conducted to analyse contributory factors for recurrence
      within 24 months.Methods: The present retrospective study was undertaken to
      analyse factors affecting recurrence, type of failure andthe follow up pattern of
      patients who completed treatment with a minimum follow-up period of 6 months
      during thestudy period of 5 years. Results: Out of 323 patients included in the
      study, 112 (34.7%) presented with recurrencewithin the follow-up period. The
      stage and histology had a significant impact on disease free survival (DFS). Of
      thosewho were followed-up regularly, recurrence was observed in 28.7% with a DFS
      of 81.3 months, in contrast to the 48.5% patients with a DFS of 45.0 months for
      whom follow-up was irregular. The failure pattern was mostly in the formof nodal
      recurrence (61%). On univariate analysis, treatment time, EBRT and ICBT gap and
      mean EQD2 point A werefound to associated with a better outcome in terms of 2yr
      DFS. On Cox regression analysis, stage, histology, treatmentgap (HR-0.48) and
      follow up pattern (HR-0.24) retained their effects on survival. Point A dose was
      higher in patientswithout recurrence (P value 0.000) unlike other assymmetric
      parameters. Conclusion: Apart from point A cumulativedose (mean EQD2), stage,
      histology and treatment gap were the factors that affected early local failure.
      An interestingresult was that follow-up pattern had a significant impact on DFS
      period.

PMID- 29373896
TI  - Differential Response of B Cells to an Immunogen, a Mitogen and a Chemical
      Carcinogen in a Mouse Model System
AB  - Background: B cells are specific antibody generating cells which respond to
      foreign intruders in the circulation.The purpose of this study was to compare the
      relative immunogenic potentials of three well established agent types viz.an
      immunogen, a mitogen and a carcinogen, by following B cell responses to their
      presence in a mouse model system.Methods: Mice were treated with tetanus toxoid
      (immunogen), poke weed mitogen (typical mitogen), and benzo-alpha-pyrene
      (carcinogen) and generated B cell populations were determined in isolated splenic
      lymphocytes (splenocytes)by flow cytometry using specific anti-B cell marker
      antibodies. Flow cytometric estimation of LDL receptor (LDLR)expression, along
      with associated B cell markers, was also conducted. Kit based estimation of serum
      IgG, westernblotting for LDLR estimation on total splenocytes and spectrometry
      for cholesterol and serum protein estimation werefurther undertaken. Student's T
      tests and one way ANOVA followed by the Bonferroni method were employed
      forstatistical analysis. Results: The mitogen was found to better stimulate B
      cell marker expression than the immunogen,although the latter was more effective
      at inducing antibody production. The chemical carcinogen benzo-alpha-pyrene atlow
      concentration acted potentially like a mitogen but almost zero immunity was
      apparent at a carcinogenic dose, witha low profile for LDLR expression and
      intracellular cholesterol. Conclusion: The findings in our study demonstratean
      impact of concentration of BaP on generation of humoral immunity. Probably by
      immunosuppression throughrestriction of B-cell populations and associated
      antibodies, benzo-alpha-pyrene may exerts carcinogenicity. The level
      ofcholesterol was found to be a pivotal target.

PMID- 29373897
TI  - Association of ARID5B Genetic Variants with Risk of Childhood B Cell Precursor
      Acute Lymphoblastic Leukaemia in Latvia
AB  - Background: Acute lymphoblastic leukaemia (ALL) is the most common malignancy in
      childhood. Despitenumerous investigations very little is still known about its
      aetiology. However, in one genome wide association studyconducted to identify the
      possible genetic risk factors, two allelic variations rs10821936 and rs10994982
      in the 3rdintron of the ARID5B gene were identified as possible ALL risk alleles.
      Association between ARID5B gene variants andALL risk was also been confirmed for
      different ethnic groups. Materials and Methods: Eight genetic variants in thegene
      ARID5B were genotyped - rs10994982, rs7908445, rs7923074, rs10821936, rs10821937,
      rs7896246, rs10821938and rs7089424 in 77 ALL patients in remission and in 122 age
      and gender matched controls; parental samples werealso genotyped in 50 cases.
      Results: Six out of the eight (rs7908445, rs7923074, rs10821936, rs10821937,
      rs7896246and rs7089424) analysed allelic variations were identified in the case
      control analysis as statistically significant riskalleles for ALL development. In
      the family study and using hybrid analysis, all allelic variations were
      significantlyassociated with ALL. During the study, risk haplotype was identified
      rs10994982/rs7908445/rs7923074/
      rs10821936/rs10821937/rs7896246/rs10821938/rs7089424 - ATACCAAG - with a
      frequency in cases of 0.17 and in the controlgroup at 0.29 (chi square = 6.69, p
      value = 0.009). In the family association study the same haplotype showed
      statisticalsignificance (chi squared = 10.3, p value = 0.001). Conclusions:
      Results of the study replicate and extend previouslypublished findings for ARID5B
      localized allelic variants, but do not explain the mechanism of action related to
      thepathogenesis of ALL.

PMID- 29373898
TI  - Anti-ROR1 scFv-EndoG as a Novel Anti-Cancer Therapeutic Drug
AB  - Aim: Immunotoxins are proteins that consist of an antibody fragment linked to a
      toxin, used as agents for targetedtherapy of cancers. Although the most potent
      immunotoxins are made from bacterial and plant toxins, obstacles whichcontribute
      to poor responses are immunogenicity in patients and rapid development of
      neutralizing antibodies. In thepresent study we proposed a new therapeutic
      immunotoxin for targeted cancer therapy of ROR1 expressing cancers:an anti ROR1
      single chain fragment variable antibody (scFv)-endonuclease G (anti ROR1 scFv
      EndoG). Methods:The three-dimensional structure of anti ROR1 scFv-EndoG protein
      was modeled and structure validation tools wereemployed to confirm the accuracy
      and reliability of the developed model. In addition, stability and integrity of
      themodel were assessed by molecular dynamic (MD) simulation. Results: All results
      suggested the protein model tobe acceptable and of good quality. Conclusions:
      Anti-ROR1 scFv-EndoG would be expected to bind to the ROR1extracellular domain by
      its scFv portion and selectively deliver non-immunogenic human endonuclease G
      enzyme asan end-stage apoptosis molecule into ROR1-expressing cancer cells and
      lead rapidly to apoptosis. We believe that antiROR1 and other anti-tumor antigen
      scFv-EndoG forms may be helpful for cancer therapy.

PMID- 29373899
TI  - Mitochondrial Effects of Teucrium Polium and Prosopis Farcta Extracts in
      Colorectal Cancer Cells
AB  - Background: Teucrium Polium and Prosopis Farcta have been traditionally employed
      in cancer treatment. In thisstudy we evaluated the effects of methanolic extracts
      of these two plants in HT-29 cells. Methods: IC50s of extractswere obtained via
      MTT assay and the levels of ROS production, cell death, collapse of mitochondrial
      membranepotential and Sirt3 enzyme activity were determined. Results: After 48
      hours exposure, IC50s for Teucrium and Prosopisextracts were 3 and 2MUg/ml,
      respectively. Extracts induced higher ROS production after 6 hours than after 12
      hours.Mitochondrial membrane potential collapse and cell death rate were also
      increased; Teucrium caused greater cell deaththan Prosopis. Extracts from both
      plants increased Sirt3 activity in its normal form, but only Teucrium extract
      caused asignificant increase in activity of Sirt3 enzyme isolated from cancer
      cells. Conclusion: Teucrium and Prosopis extractsexert anticancer activity via
      mitochondrial alterations, as exemplified by increased ROS levels, Sirt3 activity
      and celldeath in HT-29 colorectal cancer cells.

PMID- 29373900
TI  - Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinomas: A Single
      Center Study from Iran
AB  - Introduction: Lung cancer is the fifth leading tumor in Iran, and while its
      incidence remains relatively low, ithas been increasing steadily. Targeted
      therapies have brought new hope to patients with non small cell lung
      cancer(NSCLC). The epidermal growth factor receptor (EGFR) gene is the prototype
      member of the type I receptor tyrosinekinase (TK) family and plays a pivotal role
      in cell proliferation and differentiation. Studies from Asian countries
      haverevealed a higher frequency of EGFR mutations than in the West. The aim of
      this study was to measure the frequencyand type of EGFR mutations in a group of
      Iranian patients with lung adenocarcinomas. Methods: Formalin fixedparaffin
      embedded (FFPE) lung adenocarcinoma tissues from 103 Iranian patients were
      sequentially tested for EGFRmutations by the polymerase chain reaction (PCR)
      followed by direct nucleotide sequencing of exons 18, 19, 20, and21. Patient's
      demographics and other clinical details were obtained from the medical records of
      hospitals affiliated toIran University of Medical Sciences, Tehran, Iran.
      Statistical analyses were performed with SPSS v.20. Results: EGFRmutations were
      detected in 25/103 (24.3%) patients. The most frequent was an exon 21 point
      mutation (L858R) (15patients; 60%), followed by one in exon 19 (10 patients;
      40%). The frequency of EGFR mutations in never-smokerpatients was significantly
      higher than in smokers (68% versus 32%; p < 0. 01). Conclusion: EGFR mutation
      frequencyis higher than in the West but lower than in East Asian and almost equal
      to reported rates for Indian and North Africanpopulations. Smoking is negatively
      associated with EGFR mutations in Iranian lung adenocarcinomas.

PMID- 29373901
TI  - Compliance with National Guidelines on the Treatment of Stage II-IVB
      Nasopharyngeal Carcinoma in a Regional Cancer Center of Southern China
AB  - Objective: It is unknown whether the treatment provided to patients with stage II
      IVB NPC in southern Chinaadheres to the 2015 NCCN guidelines. Consequently, a
      retrospective analysis was conducted, in order to evaluatethe compliance with
      NCCN guidelines and identify the areas for improvement. Methods: The present
      study was aretrospective study that included patients with stage II-IVB NPC in
      southern China during the period 2013 and 2014.The treatment regimens were
      compared with the 2015 NCCN guidelines in order to identify potential
      noncomplianceregarding the treatment for stage II-IVB NPC. The statistical
      analyses included descriptive statistics, univariateand/or multivariate analysis
      using SPSS version 16.0.0. Results: A total of 215 patients, including 166 men
      (77.21%)and 49 women (22.79%), were involved in the analysis. Although the
      overall rate of noncompliance with the NCCNrecommendations was 23.26%, the
      noncompliance rate of concurrent chemoradiation (CCRT), induction of
      chemotherapy(IC) followed by CCRT and CCRT followed by adjuvant chemotherapy (AC)
      was 7.02%, 39.76% and 50.00%,respectively. Univariate analysis indicated that
      NCCN noncompliance regarding the treatment for stage II-IVB NPCdid not exhibit a
      significant correlation with the parameters age, gender, insurance status,
      education profile, first clinicdepartment, careers, comorbidities and overall
      clinical stage, but it indicated a significant association with the
      therapeuticschedule (P<0.05). The multivariate analysis indicated that the NCCN
      noncompliance regarding the treatment for stageII-IVB NPC exhibited a
      statistically significant difference between CCRT and CCRT followed by AC
      (OR=0.10, 95%CI 0.04-0.27, P<0.05 ), although the difference noted between CCRT
      and IC followed by CCRT was not significantlydifferent (OR=1.71, 95% CI 0.50
      5.87,P=0.40). Conclusions: The use of specific therapeutic schedules may affect
      thenoncompliance with NCCN guidelines regarding the treatment for stage II-IVB
      NPC in southern China, notably withregard to the treatment schedule of CCRT
      followed by AC.

PMID- 29373902
TI  - Beliefs and Behavior of Saudi Women in the University of Tabuk Toward Breast Self
      Examination Practice
AB  - Background: Breast cancer is one of the most frequent types of malignancy
      worldwide, Breast Self Exam (BSE)is considered as a simple method to screen and
      detect breast cancer, then early beginning of treatment and enhancingsurvival
      rates. Aim: To Identify the health beliefs about breast Self-Examination and its
      relationships with thefrequency of BSE among the women in the University of Tabuk
      at Saudi Arabia. Methods: Descriptive, cross-sectionalcorrelational design was
      used; Champion Health Beliefs Model (CHBM) was utilized to assess health beliefs
      among 400women who answered a self-administered questionnaire. Results: Among the
      400 respondents, almost all the sample(382,95.5%) heard about BSE. However, only
      (7.8%) practiced BSE regularly each month in the past year, and (9%)is intended
      to perform BSE monthly in future. There was a positive relationship between
      performing BSE last year andthe beliefs of susceptibility and confidence. While,
      intention to perform BSE in the future was significantly correlatedto seriousness
      and confidence. Perceived barriers were negatively related to BSE performance in
      last 12 months and infuture. Conclusion: Health beliefs affect the behavior of
      women in practicing BSE. Confidence was related positivelyto BSE in past year,
      and future practice, while barriers belief was as the negative factor to perform
      BSE.

PMID- 29373903
TI  - Hemostatic Abnormalities in Multiple Myeloma Patients
AB  - Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder
      characterized by clonal proliferation ofplasma cells in the bone marrow. Diverse
      hemostatic abnormalities have been reported in patients with myeloma
      whichpredispose to bleeding and also thrombosis. Methods: Complete blood count,
      biochemical parameters and parametersof hemostasis i.e. platelet count,
      prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin
      time(TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus
      anticoagulant, were assessed in 29 MM patientsand 30 age matched controls.
      Results: The most frequent abnormal screening parameter was APTT. Of the six
      indicativeof a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT,
      reduced plasma fibrinogen and factor VIII, atleast one was abnormal in 8 (27.6%)
      patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer,
      elevatedfactor VIII and plasma fibrinogen, one or more marker was present in 24
      (82.7%). D-dimer was the most commonprothrombotic marker, being elevated in 22
      (75.9%) patients. One or more laboratory parameter of hemostasis wasabnormal in
      all 29 (100%) patients. Though thrombotic complications are reported to be less
      frequent as compared tohemorrhagic manifestations, one or more marker of
      thrombosis was present in 24 (82.7%) patients. Conclusion: Thisstudy provided
      laboratory evidence of hemostatic dysfunction which may be associated with
      thrombotic or bleedingcomplications at diagnosis in all MM patients. Hence,
      screening for these abnormalities at the time of diagnosis shouldhelp improved
      prognosis in such cases.

PMID- 29373904
TI  - Eupatorin and Salvigenin Potentiate Doxorubicin-Induced Apoptosis and Cell Cycle
      Arrest in HT-29 and SW948 Human Colon Cancer Cells
AB  - Background: Cancer persists as one of the world's most pressing maladies. Notable
      points about chemotherapy aredrug side effects which are almost universally
      encountered. Emerging knowledge focusing on mechanisms of toxicitydue to
      chemotherapy has led to characterization of novel methods, including the
      exploitation of natural compounds,in combination therapies. Flavonoids are
      natural polyphenolic compounds that play protective roles against tumor
      celldevelopment. The focus of this study was apoptotic effects of two flavonoids,
      eupatorin and salvigenin, in combinationwith doxorubicin on a cellular model of
      colon cancer. Method: Upon establishing a non-effective dose of doxorubicin,and
      effective doses of eupatorin (100MUM) and salvigenin (150MUM) via MTT,
      morphological features of apoptosis weredistinguished using DAPI staining and
      cell cycle blockage in the sub-G1 phase. Apoptosis was determined by annexin/PI
      and western blotting. ROS levels and MMP were measured to show any role of
      mitochondria in apoptosis. Results:Co-administration of flavonoids with
      doxorubicin induced apoptosis via the mitochondrial pathway as
      mitochondrialmembrane potential and ROS production were changed. Annexin/PI
      analysis demonstrated that apoptosis frequencywas increased with the combination
      treatments in colon cancer cells. Finally, the combination of these flavonoids
      withdoxorubicin increased the Bax/Bcl-2 ratio, caspase-3 expression and PARP
      cleavage. Conclusion: Combination offlavonoids with doxorubicin induces apoptosis
      and enhances effect on cancer cells which might allow amelioration ofside effects
      by dose lowering.

PMID- 29373905
TI  - Significance of DNA Replication Licensing Proteins (MCM2, MCM5 and CDC6), p16 and
      p63 as Markers of Premalignant Lesions of the Uterine Cervix: Its Usefulness to
      Predict Malignant Potential
AB  - Cervical cancer continues to be a leading cancer among women in many parts of the
      world. Nation-wide screeningwith the Pap smear has not been implemented in India
      due to the lack of adequately trained cytologists. Identificationof biomarkers to
      predict malignant potential of the identified low risk lesions is essential to
      avoid excessive retestingand follow up. The current study analyzed the expression
      patterns of DNA replication licensing proteins, proliferationinhibitor protein
      p16INK4A and tumor suppresser protein p63 in cervical tissues and smears to
      assess the ability ofthese proteins to predict progression. Methods: Cervical
      smears and corresponding tissues were immunostained usingmouse monoclonal
      antibodies against MCM2, MCM5, CDC6, p16 and p63. Smears were treated with a non
      ionicsurfactant sodium deoxycholate prior to immuno-cytochemistry. The standard
      ABC method of immunohistochemistrywas performed using DAB as the chromogen. The
      immunostained samples were scored on a 0-3+ scale and stainingpatterns of smears
      were compared with those of tissue sections. Sensitivity and specificity for each
      of these markers werecalculated taking histopathology as the gold standard.
      Result: All the markers were positive in malignant and dysplasticcells. MCM
      protein expression was found to be up-regulated in LSIL, HSIL and in malignancies
      to a greater extentthan p16 as well as p63. CDC6 protein was preferentially
      expressed in high grade lesions and in invasive squamouscell carcinomas. A
      progressive increase in the expression of DNA replication licensing proteins in
      accordance withthe grades of cervical intraepithelial lesion suggests these
      markers as significant to predict malignant potential of lowgrade lesions in
      cervical smears. Conclusion: MCMs and CDC6 can be applied as biomarkers to
      predict malignantpotential of low grade lesions identified in screening
      programmes and retesting / follow up might be confined to thosewith high risk
      lesions alone so that overuse of resources can be safely avoided.

PMID- 29373906
TI  - Thai Water Lily Extract Induces B16 Melanoma Cell Apoptosis and Inhibits Cellular
      Invasion Through the Role of Cellular Oxidants
AB  - Melanoma is a cancer that is associated with a high capacity of invasion.
      Oxidative stress is recognized as cancergrowth and progression. The phytochemical
      pigments of natural products show either anti-oxidant or pro-oxidantactivity from
      the redox system. In addition, the phytophenolics also prevent cancer cell
      proliferation and progression.Objective: This study aims to investigate the
      effects of Thai water lily on cell apoptosis and cellular invasion throughthe
      role of cellular oxidants in B16 melanoma cells. Methods: The cytotoxicity and
      cell apoptosis of Thai water lilyextract treating B16 cells were performed by
      using the MTT and Annexin V/PI-flow cytometry methods, respectively. Inaddition,
      cellular oxidants and cancer cell invasion were also obtained by using DCFH-DA
      and Boyden chamber assays,respectively. Results: Thai water lily, Nymphaea
      stellate extract was shown to be markedly toxic to B16 melanomacells with IC50 =
      814 MUg/ml. The extract at 800 and 1,000 MUg/ml demonstrated pro-oxidant activity
      relating to the cellapoptosis. The low concentrations of the extract at 200 and
      400 MUg/ml showed the anti-oxidant function associatedwith the inhibitory effect
      of melanoma cell invasion. Conclusion: Thai water lily extract may play an
      important rolein bioactive work as a chemo preventive agent on the modulation of
      cellular oxidative stress-induced apoptosis andsuppressed cancer cell invasion.

PMID- 29373907
TI  - Knowledge and Practices Related to Screening for Breast Cancer among Women in
      Delhi, India
AB  - Background: Breast cancer is a major public health problem globally. The ongoing
      epidemiological, socio-culturaland demographic transition by accentuating the
      associated risk factors has disproportionately increased the incidenceof breast
      cancer cases and resulting mortality in developing countries like India. Early
      diagnosis with rapid initiationof treatment reduces breast cancer mortality.
      Therefore awareness of breast cancer risk and a willingness to undergoscreening
      are essential. The objective of the present study was to assess the knowledge and
      practices relating to screeningfor breast cancer among women in Delhi. Methods:
      Data were obtained from 222 adult women using a pretested
      selfadministeredquestionnaire. Results: Rates for knowledge of known risk factors
      of breast cancer were: family historyof breast cancer, 59.5%; smoking, 57.7%; old
      age, 56.3%; lack of physical exercise, 51.9%; lack of breastfeeding,48.2%; late
      menopause, 37.4%; and early menarche, 34.7%. Women who were aged < 30 and those
      who were unmarriedregistered significantly higher knowledge scores (p <= 0.01).
      Breast self-examination (BSE) was regularly practicedat-least once a month by
      41.4% of the participants. Some 48% knew mammography has a role in the early
      detectionof breast cancer. Since almost three-fourths of the participants
      believed BSE could help in early diagnosis of breastcancer, which is not
      supported by evidence, future studies should explore the consequences of
      promoting BSE at thepotential expense of screening mammography. Conclusion: Our
      findings highlight the need for awareness generationamong adult women regarding
      risk factors and methods for early detection of breast cancer.

PMID- 29373908
TI  - Molecular Subtypes of Indonesian Breast Carcinomas - Lack of Association with
      Patient Age and Tumor Size
AB  - Objective: Breast carcinoma (BC) is a heterogeneous disease that exhibits
      variation in biological behaviour,prognosis and response to therapy. Molecular
      classification is generally into Luminal A, Luminal B, HER2+ and
      triplenegative/basal-like, depending on receptor characteristics. Clinical
      factors that determined the BC prognosis are age andtumor size. Since information
      on molecular subtypes of Indonesian BCs is limited, the present study was
      conducted,with attention to subtypes in relation to age and tumor size. Methods:
      A retrospective cross-sectional study of 247paraffin-embedded samples of invasive
      BC from Dr. Sardjito General Hospital Yogyakarta in the year 2012- 2015
      wasperformed. Immunohistochemical staining using anti- ER, PR, HER2, Ki-67 and CK
      5/6 antibodies was applied toclassify molecular subtypes. Associations with age
      and tumor size were analyzed using the Chi Square Test. Results:The Luminal A was
      the most common subtype of Indonesian BC (41.3%), followed by triple negative
      (25.5%), HER2(19.4%) and luminal B (13.8%). Among the triple negative lesions,
      the basal-like subtype was more frequent than thenon basal-like (58.8 % vs
      41.2%). Luminal B accounted for the highest percentage of younger age cases (< 40
      yearsold) while HER2+ was most common in older age (> 50 years old) patients.
      Triple negative/basal-like were commonlylarge in size. Age (p = 0.080) and tumor
      size (p = 0.462) were not significantly associated with molecular subtypes ofBC.
      Conclusion: The most common molecular subtype of Indonesian BC is luminal A,
      followed by triple-negative,HER2+ and luminal B. The majority of triple-negative
      lesions are basal-like. There are no association between ageand tumor size with
      molecular subtypes of Indonesian BCs.

PMID- 29373909
TI  - Congenital Hypertrophy of Retinal Pigment Epithelium for Diagnosis of Familial
      Adenomatous Polyposis - the First FAP registry in Iran
AB  - Objective: Familial adenomatous polyposis (FAP), an autosomal dominant inherited
      disorder is characterized by thepresence of multiple adenomatous colorectal
      polyps, which can develop into cancer during early adulthood. Therefore,early
      diagnosis is essential. Most FAP patients have several extracolonic
      manifestations, including congenital hypertrophyof the retinal pigment epithelium
      (CHRPE). Whereas genetic markers may provide the main route to detection of
      ''atrisk'' subjects , at present this approach is clearly limited and searches
      for a noninvasive phenotypic marker continueto be high priority.The aim of this
      study was to describe the pattern of distribution of CHRPE lesions and
      evaluatetheir diagnostic value in FAP patients and their family members in a
      local population. Methods: A total of 23 FAPpatients and 26 relatives belonging
      to 12 families at high risk of developing FAP were subjected to colonoscopic
      andophthalmological examination. Result: Retinal examinations demonstrated
      prevalences of CHRPE in FAP patents andtheir siblings of 78% and 38%,
      respectively. We were able to illustrate a significant correlation between FAP
      diseaseand the presence of retinal lesions. Sensitivity and specificity of CHRPE
      as a screening test to detect the presence ofFAP are 78.3% and 61.5%,
      respectively, with a positive predictive value of 64.3% and a negative predictive
      value of76.2 %. A "lesion form" significant difference was found between FAP and
      normal participants.Spearman nonparametricanalysis revealed no correlation
      between age and number or size of lesions. Conclusion: Multiple CHRPE lesions
      area diagnostic feature of FAP patients They are specific and sensitive clinical
      markers of this disease (specificity 60%and sensitivity 77%).

PMID- 29373910
TI  - Expression of VEGF and Cox-2 in Patients with Esophageal Squamous Cell Carcinoma
AB  - Esophageal cancer is a highly aggressive neoplasm. In Brazil, it is the sixth
      most frequent among men and fifteenthamong women. The most common type is
      squamous cell carcinoma (SCC), responsible for 96% of cases. Twenty
      eightspecimens of Esophael squamous cell carcinoma (ESCC) were obtained by
      surgery procedures.The tissues werefixed in formalin and embedded in paraffin. In
      each case, all available hematoxylin and eosin stained sections wereexamined and
      a representative block was selected. The ages of these patients ranged from 40 to
      93 years, with a meanage of 60 years. Results: The histological grade of tumors
      was 4 well-differentiated, 19 moderately differentiated and5 poorly
      differentiated. Expression of Cox-2 and VEGF in ESCC was demonstrated in 23
      (82,14%) and 13 (44,43%)cases, respectively. Adjacent normal mucosa was positive
      in 11 (39,29%) samples and 9 (32,15%) samples for Cox-2and VEGF, respectively. No
      relationship between the expression of Cox-2 and VEGF with the
      clinicopathologicalparameters, including gender, age, surgical margin, lymph node
      status and tumor differentiation. The median follow-upperiod was 60 months.
      Survival analysis of patients with ESCC showed no relationship with the
      expression of Cox-2and VEGF. Conclusion: VEGF and Cox-2 are expressed in ESCC.
      Cox-2, VEGF, play a significant role in the originand development of ESCC and the
      inhibitors of these proteins could prove to be an important therapeutic tool in
      thecontrol of this disease.

PMID- 29373911
TI  - Can Histological Grade and Mitotic Index Replace Ki67 to Determine Luminal Breast
      Cancer Subtypes?
AB  - Introduction: Breast cancer can be classified into subtypes based on
      immunohistochemical markers, with Ki67expression levels being used to divide
      luminal BC tumors in luminal A and B subtypes; however, Ki67 is not
      routinelydetermined due to a lack of standardization. Objective: To evaluate
      histological grade and Eliminate: the mitotic indexto determine if they can be
      used as an alternative method to Ki67 staining for luminal subtype definition.
      Methods:We evaluated estrogen receptor positive breast cancer tissue samples.
      Pathological analysis included determinationof Ki67. A low level of Ki67 was
      defined as <14% positive cells. Results: We evaluated 151 breast cancer
      samples;24 (15,9%) were classified as I; 74 as HG II (49%), and 53 (35,1%) as HG
      III. The median value for Ki67 was 13%(range: <1% - 82%) and for MI was 2 (0-12).
      Histological grade I tumors exhibited Ki67 values significantly lower thanHG II
      and III tumors (Anova, Tamhane test p=0,001). A higher Ki67 value was related to
      a higher MI (Rho Spermanp=0,336; R2= 0,0273). ROC curve analysis determined that
      a MI >= 3 had a sensibility of 61.9% and specificity of66.7% in predicting a high
      Ki67 value (>=14%) (area under the curve: 0,691; p =0,0001). A HG I tumor or HG
      II-IIIwith MI <=2, had a high probability of corresponding to a LA tumor (76,3%),
      as defined using Ki67 expression, whilethe probability of a LB subtype was higher
      with HG II-III and a MI >=3 (57.4%). Global discrimination was 68.1%.Conclusions:
      For the LA subtype, our predictive model showed a good correlation of HG and MI
      with the classificationbased on Ki67<14%. In the LB subtype, the model showed a
      weak correlation; therefore Ki67 determination seems tobe needed for this group
      of patients.

PMID- 29373912
TI  - Molecular Subtypes, Apoptosis and Proliferation Status in Indonesian Diffuse
      Large B-Cell Lymphoma Cases
AB  - Objective: The diffuse large B-cell lymphoma (DLBCL) has two major molecular
      subtypes, germinal centerB-cell-like (GCB) and non-GCB. These have differing
      behavior which affects overall patient survival. However,immunohistochemistry
      based molecular subtyping of Indonesian DLBCLs has been limited. This was the
      focus of thepresent study, with a focus of attention on the apoptotic index (AI)
      and the proliferation index (PI) of the two molecularsubtypes. Materials and
      Methods: During the study period of 3.5 years, a total of 98 cases of DLBCL were
      identified.Molecular subtypes and PI were determined by immunohistochemistry and
      TUNEL method was used to determinethe AI. Result: GCB accounted for 31 cases
      (31.6%) and non-GCB the remainder (68.4%). Gender showed a slightmale
      predominance (54 cases, 55.1%), with a higher incidence in the extra-nodal region
      (57 cases, 58.2%). The AIand PI were significantly higher in GCB (p<0.001 in the
      Mann-Whitney test) and a Spearman correlation coefficienttest showed that PI was
      positively correlated with AI (r=0.673, p<0.001). Conclusion: The findings
      indicate that thenon-GCB subtype is more common than GCB in Indonesian DLBCL. GCB
      features significantly higher PI and AI,which themselves appear linked.

PMID- 29373913
TI  - Evaluation of HPV DNA positivity in colorectal cancer patients in Kerman,
      Southeast Iran
AB  - Background: The HPV virus is known to be oncogenic and associations with many
      cancers has been proven.Although many studies have been conducted on the possible
      relationship with colorectal cancer (CRC), a definitiverole of the virus has yet
      to be identified. Method: In this cross-sectional study, the frequency of HPV
      positivity in CRCsamples in Kerman was assessed in 84 cases with a mean age of
      47.7 +/- 12.5 years over two years. Qualitative realtime PCR was performed using
      general primers for the L1 region of HPV DNA. Results: Out of 84 CRC samples,
      19(22.6%), proved positive for HPV DNA. Genotyping of positive samples showed all
      of these to be of high risk HPVtype. Prevalence of HPV infection appears to
      depend geographic region, life style, diet and other factors. Conclusion: Inour
      location frequency of CRC is low, and this limited the sample size for evaluation
      of HPV DNA. The most prevalenttypes were HPV types 51 and 56. While HPV infection
      may play an important role in colorectal carcinogenesis, thisneeds to be assessed
      in future studies.

PMID- 29373914
TI  - Genetic Polymorphism of Thiopurine S-methyltransferase in Children with Acute
      Lymphoblastic Leukemia in Jordan
AB  - Background and Aims: It has been demonstrated that homozygote and heterozygote
      mutant allele carriers forthiopurine S-methyltransferase (TPMT) are at high risk
      of developing myelosuppression after receiving standard dosesof 6-mercaptopurine
      (6-MP). The aim of this study was to determine the frequency of TPMT deficient
      alleles in childrenwith acute lymphoblastic leukemia (ALL) in Jordan and to
      compare it with other ethnic groups. Methods: We included52 ALL childhood cases
      from King Hussein Cancer Research Center in Jordan. Genotyping of the rs1800460,
      rs1800462,and rs1142345 SNPs was performed by polymerase chain reaction (PCR)
      followed by sequencing. Comparisons weremade with historical data for controls
      and for both volunteers and cases from other middle-eastern countries.
      Results:Mutant TPMT alleles were present in 3.8% (2/52) of patients. Allelic
      frequencies were 1.0% for both TPMT*B andTPMT*C. None of the patients were
      heterozygous or homozygous for TPMT*3A or TPMT *2. We did not find
      statisticallysignificant differences in the distribution of mutant alleles
      between Jordan and other middle-eastern countries for bothhealthy volunteers or
      ALL patients. Conclusions: The overall frequency of TPMT mutant alleles was low
      and did notexhibit differences compared to other middle-eastern countries,
      including Jordanian studies assessing TPMT mutantalleles in healthy volunteers.
      The current results question the value of TPMT genotyping in the Jordanian
      population.

PMID- 29373915
TI  - RapidArc vs Conventional IMRT for Head and Neck Cancer Irradiation: Is Faster
      Necessary Better?
AB  - Purpose: The aim of this study was to dosimetrically evaluate and compare double
      arc RapidArc (RA) withconventional IMRT (7 fields) plans for irradiation of
      locally advanced head and neck cancers (LAHNC), focusing ontarget coverage and
      doses received by organs at risk (OAR). Methods: Computed tomography scans of 20
      patientswith LAHNC were obtained. Contouring of the target volumes and OAR was
      done. Two plans were made for eachpatient, one using IMRT and the other double
      arc RA, and calculated doses to planning target volume (PTV) and OARwere
      compared. Monitor units for each technique were also calculated. Results: PTV
      coverage was similar with bothtechniques. The homogeneity index (HI) was higher
      for the IMRT plans with a value of 0.108 +/- 0.021 compared to0.0975 +/- 0.017
      for double arc RA plans (p-value of 0.540). The double arc RA plans achieved a
      better conformitywith a CI95%= 1.01 +/- 0.021 compared to 1.05 +/- 0.057 achieved
      with the IMRT plans (p-value of 0.036). The averagemonitor units (MU) +/-SD were
      930.5 +/- 142.42 for the IMRT plans as opposed to 484.25 +/- 69.47 for the double
      arc RAplans (P-value of 0.002). Double arc plans provided better OAR sparing with
      a significant p-value of 0.002 and 0.004for the right and left parotid glands,
      respectively. Conclusions: RA is a rapid and accurate technique that uses
      lowerMUs than conventional IMRT. Double arc plans provide better dose conformity,
      OAR sparing and a more homogeneoustarget coverage compared to IMRT.

PMID- 29373916
TI  - Intra-Operative Frozen Sections for Ovarian Tumors - A Tertiary Center Experience
AB  - Background: Accuracy of diagnosis with intra-operative frozen sections is
      extremely important in the evaluationof ovarian tumors so that appropriate
      surgical procedures can be selected. Study design: All patients who withintra
      operative frozen sections for ovarian masses in a tertiary center over nine years
      from June 2008 until April 2017were reviewed. Frozen section diagnosis and final
      histopathological reports were compared. Main outcome measures:Sensitivity,
      specificity, positive and negative predictive values of intra-operative frozen
      section as compared to finalhistopathological results for ovarian tumors.
      Results: A total of 92 cases were recruited for final evaluation. The
      frozensection diagnoses were comparable with the final histopathological reports
      in 83.7% of cases. The sensitivity, specificity,positive predictive value and
      negative predictive value for benign and malignant ovarian tumors were 95.6%,
      85.1%,86.0% and 95.2% and 69.2%, 100%, 100% and 89.2% respectively. For
      borderline ovarian tumors, the sensitivity andspecificity were 76.2% and 88.7%,
      respectively; the positive predictive value was 66.7% and the negative
      predictivevalue was 92.7%. Conclusion: The accuracy of intra-operative frozen
      section diagnoses for ovarian tumors is highand this approach remains a reliable
      option in assessing ovarian masses intra-operatively.

PMID- 29373917
TI  - Immunohistochemical and Biochemical Expression Patterns of TTF-1, RAGE, GLUT-1
      and SOX2 in HCV-Associated Hepatocellular Carcinomas
AB  - Objective: To investigate the expression of TTF-1, RAGE, GLUT1 and SOX2 in HCV
      associated HCCs and insurrounding non-tumorous liver tissue. Material and
      Methods: Tissue material from partial hepatectomy cases forHCC along with
      corresponding serum samples and 30 control serum samples from healthy volunteers
      were studied.Biopsies were classified into: non-tumor hepatic tissue (36
      sections); HCC (33 sections) and liver cell dysplasia(LCD) (15 sections). All
      cases were positive for HCV. Immunohistochemistry (IHC), gene extraction and
      quantitativereal-time reverse-transcription assays (qRT-PCR) were applied.
      Results: By IHC, LCD and HCC showed significantlyhigh percentages of positive
      cases with all markers. SOX2 showed significant increase with higher HCC grades,
      whileRAGE demonstrated an inverse relation and GLUT-1 and TTF-1 lacked any
      correlation. In nontumorous-HCV tissue,we found significantly high TTF-1, low
      RAGE and negative SOX2 expression. RAGE, GLUT-1 and SOX2 shownon-significant
      elevation positivity in high grade HCV compared to low grade lesions. TTF-1, RAGE
      and SOX2exhibited low expression in cirrhosis compared to fibrosis. Biochemical
      studies on serum and tissue extracts revealedsignificant down-regulation of RAGE,
      GLUT-1 and SOX2 genes, as well as significant up-regulation of the TTF-1gene in
      HCC cases compared to controls. All studied genes show significant correlation
      with HCC grade. In non-tumortissue, only TTF-1 gene expression had a significant
      correlation with the fibrosis score. Conclusion: Higher expressionof TTF-1, RAGE,
      GLUT-1 and SOX2 in HCC and dysplasia compared to non-tumor tissues indicates up
      regulation ofthese markers as early events during the development of HCV
      associated HCC.

PMID- 29373918
TI  - Carbon Footprint in Flexible Ureteroscopy: A Comparative Study on the
      Environmental Impact of Reusable and Single-Use Ureteroscopes.
AB  - PURPOSE: There are no comparative assessments on the environmental impact of
      endourologic instruments. We evaluated and compared the environmental impact of
      single-use flexible ureteroscopes with reusable flexible ureteroscopes. PATIENTS
      AND METHODS: An analysis of the typical life cycle of the LithoVueTM (Boston
      Scientific) single-use digital flexible ureteroscope and Olympus Flexible Video
      Ureteroscope (URV-F) was performed. To measure the carbon footprint, data were
      obtained on manufacturing of single-use and reusable flexible ureteroscopes and
      from typical uses obtained with a reusable scope, including repairs, replacement
      instruments, and ultimate disposal of both ureteroscopes. The solid waste
      generated (kg) and energy consumed (kWh) during each case were quantified and
      converted into their equivalent mass of carbon dioxide (kg of CO2) released.
      RESULTS: Flexible ureteroscopic raw materials composed of plastic (90%), steel
      (4%), electronics (4%), and rubber (2%). The manufacturing cost of a flexible
      ureteroscope was 11.49 kg of CO2 per 1 kg of ureteroscope. The weight of the
      single-use LithoVue and URV-F flexible ureteroscope was 0.3 and 1 kg,
      respectively. The total carbon footprint of the lifecycle assessment of the
      LithoVue was 4.43 kg of CO2 per endourologic case. The total carbon footprint of
      the lifecycle of the reusable ureteroscope was 4.47 kg of CO2 per case.
      CONCLUSION: The environmental impacts of the reusable flexible ureteroscope and
      the single-use flexible ureteroscope are comparable. Urologists should be aware
      that the typical life cycle of urologic instruments is a concerning source of
      environmental emissions.

PMID- 29373919
TI  - Communicating the unknown: descriptions of pictured scenes and events presented
      on video by children and adolescents using aided communication and their peers
      using natural speech.
AB  - The facility to describe scenes and events is important in everyday
      communication, but little is known about the description skills and strategies of
      young people using aided communication. This article explores how 81 children and
      adolescents using aided communication and 56 peers using natural speech, aged 5
      15 years, described pictured scenes and events presented on video to a partner
      who had no prior knowledge of the content. The group who used aided communication
      took longer and included fewer elements in their descriptions than the reference
      group; however, the groups did not differ in their use of irrelevant or incorrect
      elements, suggesting that both groups stayed on topic. Measures related to aided
      message efficiency correlated significantly with measures of spoken language
      comprehension. There were no significant differences between groups for their
      descriptions of pictured scenes and video events. Analyses showed both
      unpredicted group similarities and predictable differences, suggesting key
      components for future research consideration.

PMID- 29373920
TI  - Contralateral lumbosacral plexopathy following lumbar microdiscectomy.
AB  - We describe the unique case of a 51-year-old lady who developed a contralateral
      lumbosacral plexopathy two days after a lumbar microdiscectomy. This is the first
      report to date of this complication occurring following this procedure. We review
      the literature regarding lumbosacral plexopathy and discuss the evidence base
      behind investigating and managing this condition and the potential
      pathophysiological mechanisms which underlie its development. We draw comparisons
      with the more widely recognised post-operative brachial neuritis, characterised
      by delayed onset brachial plexopathy developing after cervical decompression, and
      propose an immune-mediated inflammatory mechanism linking the two conditions.

PMID- 29373921
TI  - "Understanding my ALS". Experiences and reflections of persons with amyotrophic
      lateral sclerosis and relatives on participation in peer group rehabilitation.
AB  - PURPOSE: The aim of this study was to gain insight into experiences and
      reflections of persons with amyotrophic lateral sclerosis and relatives
      concerning the peer group rehabilitation programme "More Life - Less Illness".
      METHODS: This qualitative study used the Interpretive Description methodology
      with Symbolic Interactionism as the analytical framework. Eighteen programme
      participants representing persons with amyotrophic lateral sclerosis (n = 8) and
      relatives (n = 10) were included. Data consisted of individual interviews and
      participant observation. RESULTS: The analysis revealed two categorical themes,
      "Sense of Community Building" and "Understanding my ALS", which represented the
      participants' experiences and reflections on peer group rehabilitation. Through
      the analysis, it became apparent that "Sense of Community Building" gave rise to
      an increased and personalised understanding of amyotrophic lateral sclerosis
      among the participants. As a part of the continuous processing of the knowledge
      gained, "Facing Facts" and "Retaining Normality" appeared as subthemes regarding
      the participants' ability to live a less dependent and more meaningful life.
      CONCLUSIONS: This study of peer group rehabilitation for persons with amyotrophic
      lateral sclerosis and relatives indicates that programme participation leads to
      positive experiences in terms of living a shared meaningful life despite severe
      disability. The findings may guide practice to develop longitudinal peer group
      rehabilitation programmes with joint inclusion of persons with amyotrophic
      lateral sclerosis and relatives. Implications for Rehabilitation Peer group
      rehabilitation may facilitate an increased and personalised understanding of what
      it means to live with amyotrophic lateral sclerosis. A programme design with six
      months of sequential sessions enables a continuous processing of shared
      experiences and gained knowledge. Joint participation of persons with amyotrophic
      lateral sclerosis and their relatives supports both their internal relationship
      and social networking. Peer group rehabilitation in amyotrophic lateral sclerosis
      should help overcome obstacles concerning the needs of participants,
      accessibility, and geographical distance.

PMID- 29373922
TI  - Development and biological evaluation of vesicles containing bile salt of
      telmisartan for the treatment of diabetic nephropathy.
AB  - The aim of present study was to develop and evaluate vesicles containing bile
      salt formulation of telmisartan for the treatment of diabetic nephropathy.
      Different vesicles containing bile salt formulations were developed by varying
      ratios of soybean phosphatidylcholine and sodium deoxycholate. Prepared
      formulations were characterized for their size, polydispersity index, zeta
      potential, morphology and entrapment efficiency. Further, the renoprotective
      outcome of optimized formulation was studied in streptozotocin-induced diabetic
      nephropathy rat model. Results of the present study demonstrated that the average
      vesicles size, polydispersity index, zeta potential and entrapment efficiency
      were found to be in the range of 64.98 +/- 1.40 to 167.60 +/- 6.46 nm, 0.02 +/-
      0.04 to 0.31 +/- 0.01, -24.30 +/- 1.39 to -42.60 +/- 6.67 mV and 29.68 +/- 1.08%
      to 77.21 +/- 0.52%, respectively. Further, the best chosen formulation F4
      presented vesicles size, polydispersity index, zeta potential and entrapment
      efficiency of 64.98 +/- 1.40 nm, 0.24 +/- 0.02, -35.40 +/- 1.48 mV and 77.21 +/-
      0.52%, respectively. In addition, formulation F4 improved the biological indices
      in streptozotocin-induced diabetic nephropathy in rats. It was concluded that
      prepared formulation exerts a valuable results on diabetic nephropathy and it may
      be a potential pharmaceutical dosage form for the treatment of diabetic
      nephropathy.

PMID- 29373923
TI  - A Unique Case of Cutaneous Larva Migrans Acquired Within the Province of Quebec
      and Successfully Treated With Topical Ivermectin.
AB  - Cutaneous larva migrans (CLM) is a zoonotic helminthiasis frequently imported to
      Canada by travellers to beach destinations in the tropics. The preferred
      treatment is oral ivermectin. We present a case of CLM acquired within the
      province of Quebec, a first in our provincial health records. Our case also puts
      forward the use of topical ivermectin as a possibly effective CLM treatment
      approach as our patient was successfully treated with 1 month of an ivermectin 1%
      cream applied locally twice daily.

PMID- 29373924
TI  - Efficacy and Safety of Apremilast Monotherapy for Moderate to Severe Psoriasis:
      Retrospective Study.
AB  - BACKGROUND: Apremilast is a new oral drug for the treatment of moderate to severe
      plaque psoriasis that reduces inflammation by inhibiting phosphodiesterase 4. Its
      efficacy and safety data are limited; hence, real-world outcomes are important
      for elucidating the full spectrum of its adverse events (AEs) and expanding
      generalizability of clinical trial findings. OBJECTIVE: Assess the efficacy and
      safety of apremilast monotherapy in real-world practice. METHODS: A retrospective
      chart review was conducted in 2 academic dermatology practices. Efficacy was
      measured as the proportion of patients achieving a >=75% reduction from baseline
      Psoriasis Area and Severity Index score (PASI-75) or a Psoriasis Global
      Assessment (PGA) score of 0 (clear) or 1 (almost clear) at 16 weeks. Safety was
      measured as the proportion of patients reporting >=1 AE at 16 weeks. RESULTS:
      Thirty-four patients were included. EFFICACY: 19 patients (55.9%) achieved PASI
      75 or PGA 0/1. SAFETY: 23 patients (67.6%) experienced >=1 AEs. Five patients
      (14.7%) withdrew treatment prior to week 16 due to AEs. One patient withdrew
      treatment due to mood lability and depression. Common AEs included headache
      (32.4%), nausea (20.6%), diarrhoea (14.7%), weight loss (8.8%), and loose stool
      (8.8%). CONCLUSION: Apremilast monotherapy had higher efficacy with similar
      safety outcomes in the real world compared to clinical trials. There were higher
      proportions of reported headaches compared to clinical trials. This study
      supports the apremilast monotherapy clinical trial findings, suggesting that it
      has an acceptable safety profile and significantly reduces the severity of
      moderate to severe plaque psoriasis. Limitations include the retrospective nature
      of the study.

PMID- 29373925
TI  - Disseminated Eczema Following Radiotherapy: A Case Report.
AB  - BACKGROUND: Radiotherapy-induced acute skin reactions are common and an expected
      effect of radiotherapy. Eczematous eruptions, however, are rarely reported, with
      disseminated eczema in particular being infrequently seen and likely
      underrecognized. OBJECTIVE: We present a unique case of disseminated vesicular
      eczema following radiotherapy for ductal carcinoma in situ. CONCLUSIONS: The
      development of a localized vesicular eruption with subsequent dissemination can
      occur following radiotherapy. The mechanism of autosensitization is poorly
      understood but likely involves a cell-mediated immune response. Recognition is
      important to prevent excessive and inappropriate investigation and treatment.

PMID- 29373926
TI  - Treatment of Knee Osteoarthritis with Bone Marrow-Derived Mononuclear Cell
      Injection: 12-Month Follow-up.
AB  - Objectives To evaluate the main symptoms of knee osteoarthritis (OA) and tissue
      structure changes after a single dose bone marrow-derived mononuclear cell (BM
      MNC) intra articular injection. Case series study. Patients with knee OA Kellgren
      Lawrence (K-L) grade II and III received 1 injection of BM MNC. The clinical
      results were analyzed with the Knee injury and Osteoarthritis Outcome Score
      (KOOS) and Knee Society Score (KSS) before, 3, 6, and 12 months after injection.
      Radiological evaluation was performed with a calibrated x-ray and the magnetic
      resonance (MR) imaging before and 6 to 7 months postinjection. Results A total of
      34 knees were treated with BM MNC injections. Mean (+/-SD) age of patient group
      was 53.96 +/- 14.15 years; there were 16 males, 16 females, KL grade II, 16; KL
      grade III, 18. The average injected count of BM MNCs was 45.56 +/- 34.94 * 106
      cells. At the endpoint of 12 months 65% of patients still had minimal perceptible
      clinical improvement of the KOOS total score. The mean improvement of KOOS total
      score was +15.3 and of the KSS knee score was +21.45 and the function subscale
      +27.08 ( P < 0.05) points. The Whole Organ Magnetic Resonance Imaging Score
      (WORMS) improved from 44.31 to 42.93 points ( P < 0.05). No adverse effects after
      the BM-MNC injection were observed. Conclusions The single dose BM MNC partially
      reduces clinical signs of the knee osteoarthritis stage II/III and in some cases,
      decreases degenerative changes in the joint building tissue over 12-month period.

PMID- 29373927
TI  - Comparative study of oral lipid nanoparticle formulations (LNFs) for chemical
      stabilization of antitubercular drugs: physicochemical and cellular evaluation.
AB  - Rifampicin (RIF) and Isoniazid (INH) are two major first-line antitubercular
      drugs (ATDs) that are typically administered orally, in combination. However, INH
      catalysed degradation of RIF under acidic pH environment of the stomach is a
      major concern related to its oral delivery, and is dramatically accelerated upon
      further exposure to and interaction with INH. This interaction, in turn, triggers
      a direct decline in the available RIF dose below the sub-therapeutic level,
      thereby diminishing its therapeutic efficacy. We hypothesized that encapsulation
      of both these important ATDs into lipid nanoparticle formulations (LNFs) may help
      mitigate the acid hydrolysis of RIF, its subsequent interaction with INH and its
      eventual INH-mediated accelerated chemical degradation in the gastric
      environment. We further hypothesized that these LNFs would be capable of enhanced
      uptake and localization into intra-cellular compartments of lung macrophages,
      thereby potentially targeting the Tb pathogen in its in vivo niche. For this
      purpose, we evaluated two promising LNFs, viz., solid lipid nanoparticles (SLNs)
      and nanostructured lipid carriers (NLCs) for encapsulating these ATDs. Here, we
      report on the design, development and comparative evaluation of SLN and NLC-based
      lipid formulations of both INH and RIF. Our strategy of nanoencapsulation
      substantially prolonged encapsulated RIF release and improved its chemical
      stability in presence of INH in a simulated gastric acidic environment. In vitro
      cell culture studies showed a well-quantifiable uptake of LNFs in a human
      alveolar macrophage cell line. Overall, these evaluations provided promising
      results for establishing the potential of both formulations for TB therapy.

PMID- 29373928
TI  - Three new Lycopodium alkaloids from Lycopodium japonicum.
AB  - Three new Lycopodium alkaloids (1-3), together with 15 known alkaloids, were
      isolated from club moss Lycopodium japonicum. Their structures were determined by
      extensive spectroscopic analysis, including 1D and 2D NMR spectra. Compound 1 has
      an unusual beta-oriented methyl group substituted at C-15 and an alpha-hydroxy
      cyclopentenone moiety. All new alkaloids were evaluated for the inhibition of T
      type calcium channel.

PMID- 29373929
TI  - Third-Generation Human Epidermal Growth Factor Receptor 2 Chimeric Antigen
      Receptor Expression on Human T Cells Improves with Two-Signal Activation.
AB  - Patient derived T cells activated ex vivo with CD3/CD28 beads show superior
      expansion. Therefore, CD3/CD28 beads have huge potential to be used in the clinic
      for immunotherapy applications. Two protocols were devised to evaluate if the
      expression of third-generation human epidermal growth factor receptor 2 chimeric
      antigen receptor (CAR) can be improved on human T cells activated with CD3/CD28
      beads. In protocol 1, unconcentrated human epidermal growth factor receptor 2 CAR
      retroviral supernatants were used, and in protocol 2, concentrated virus was
      used. The results demonstrate that compared to unconcentrated viral supernatants,
      transduction with the concentrated virus improved the infection rate of bead
      activated CD4 T cells from ~40% to ~70%, and the fluorescent intensity values
      improved from ~12,000 to ~28,000 mean fluorescence intensity units. These results
      demonstrate the utility of these protocols for CAR immunotherapies.

PMID- 29373930
TI  - Does progesterone to oocyte index have a predictive value for IVF outcome? A
      retrospective cohort and review of the literature.
AB  - The potential adverse effect of Serum progesterone (SP) elevation on the day of
      hCG administration is a matter of continued debate. Our study aimed to evaluate
      the relative value of progesterone to a number of aspirated oocytes ratio (POI)
      to predict clinical pregnancy (CP) and live birth (LB) in fresh IVF cycles and to
      review the relevant literature. A retrospective analysis of GnRH Antagonist IVF
      ET cycles. POI was calculated by dividing the SP on the day of hCG by the number
      of aspirated mature oocytes. A multivariate logistic regression analysis was
      performed to evaluate the predictive value of POI for CP and LB. Cycle outcome
      parameters included clinical pregnancy, live-birth and miscarriage. A total of
      2,693 IVF/ICSI cycles were analyzed. POI was inversely associated with CP
      adjusted OR 0.063 (95% CI 0.016-0.249, p < .001) and with LB adjusted OR 0.036
      (95% CI 0.007-0.199, p < .001). For prediction of LB, the area under the curve
      (AUC) was 0.68 (95% CI 0.64-0.71, p < .001) for the POI model. POI above the 90th
      percentile with a value of 0.36 ng/mL/oocyte results in CP and LB rates of 8.0
      and 5.9%, respectively. POI is a simple index for the prediction of IVF-ET cycle
      outcomes, it can advocate a limit above which embryo transfer should be
      reconsidered.

PMID- 29373931
TI  - Neurosurgical image: giant pituitary adenoma and multiple aneurysms.
AB  - Pituitary adenomas are associated with intracranial aneurysms. Giant non
      functioning pituitary adenomas with aneurysms in their vicinity pose technical
      surgical challengesas aneurysm rupture can be catastrophic during surgery. We
      present the case of a middle aged women who presented with progressive visual
      loss in both eyes caused by a giant pituitary adenoma compressing the optic
      chiasma. She also had associated mirror image carotid aneurysms embedded in the
      tumour. They were successfully coiled preoperatively and the tumour was removed
      safely with improvement of her symptoms.

PMID- 29373932
TI  - Challenging predictions between affective temperaments, depression and anxiety in
      a Kosovo student community sample.
AB  - OBJECTIVE: The relationship between temperament and mental health problems is
      seen very important as we hope to explain the trajectory of this interaction. The
      aim of this study was to test the validity of affective temperaments for
      predicting psychiatric morbidity, by explaining the relationships between
      temperament, anxiety and depression in a community sample. METHODS: This was a
      cross-sectional study. The present sample consisted of 960 participants (347
      male, 622 female) with a mean age of M = 28.4 (SD = 10) randomly recruited.
      Affective temperaments were measured by the brief version of TEMPS-A, depression
      and anxiety measured with Beck Depression Inventory and Beck Anxiety Inventory.
      RESULTS: The Cronbach alpha reliability coefficients for affective temperaments
      were between .72 and .81, for BDI and BAI, were .88 and .90. The study found
      significant gender differences on depressive [t(959) = -4.2, p<.001], cyclothymic
      [t(957) = -4.6, p < .001] and anxious temperament [t(957) = -8.2, p < .001],
      females having higher scores than males, and reverse results on hyperthermic
      temperament [t(958) = 2.1, p < .045], males having higher scores than females. No
      gender difference is found in irritable temperament [t(955) = -.581, p < .561].
      Affective temperaments were found significant predictors for depression and
      anxiety. The combination of the depressive temperament and cyclothymic
      temperament explained the 32% variance of depression and the 25% variance of
      anxiety. CONCLUSIONS: Study findings are consistent with some other studies and
      stress the importance of screening for effective temperament in order to early
      identify depression and anxiety. Further investigation is needed to understand
      what are other factors that influence the relationship between affective
      temperaments with depression and anxiety.

PMID- 29373934
TI  - Investigating relations among stress, sleep and nail cortisol and DHEA.
AB  - In the current study, we present data investigating the relationships among
      stress, sleep disturbance, self-control, and levels of cortisol (CORT) and
      dehydroepiandrosterone (DHEA) in fingernail clippings. Currently, hair CORT is
      the only routinely used noninvasive, validated, biomarker of chronic exposure to
      stress-related hormones. Nail clippings represent an important potential
      alternative sample matrix for assessing chronic hormone exposure, as it offers a
      different timeline of hormone incorporation than scalp hair, and may be
      obtainable from populations in which hair either is lacking or is unavailable for
      cultural reasons. Moreover, there is established precedent for using fingernail
      clippings to attain biomarker data. However, the value of nail hormone assessment
      for psychological research is currently unknown due to a paucity of information
      on the relations between nail hormone concentrations and environmental or
      psychological variables. In the present study, we collected data from a low
      income, minority population (N = 47; 97% African American) to demonstrate
      feasibility and acceptability of nail collection and analysis of the adrenal
      steroids CORT and DHEA. Participants reported on perceived stress, sleep and self
      control abilities. Correlational analyses suggest that exposure to stressful
      events, disturbances in sleep and waking were associated with higher levels of
      nail DHEA, while self-control was associated with higher levels of nail CORT. We
      discuss the potential importance of this methodology for investigating
      biological, behavioral, and subjective indices of stress and well-being.

PMID- 29373933
TI  - Outcomes of clients in need of intensive team care in Flexible Assertive
      Community Treatment in Sweden.
AB  - BACKGROUND: Flexible Assertive Community Treatment (Flexible ACT) has been
      implemented in Sweden during recent years due to increasing interest in
      integrated services for people with severe mental illness. To date, few studies
      have been done on Flexible ACT effectiveness. AIMS: The overall aim of this study
      was to explore the extent to which clients assigned to the Flexible ACT board for
      ACT intensive care were stabilized with improved everyday functioning, social
      outcomes, and changes in healthcare use. METHODS: Ninety-three participants with
      psychosis, in need of ACT from six newly started Flexible ACT teams, were
      included. Data were collected using the Social Outcome Index scale (SIX),
      Practical and Social Functioning Scale, and a healthcare usage questionnaire.
      RESULTS: There was a significant positive change in everyday functioning and in
      the SIX-item 'friendship' at 18-months follow-up. A positive correlation was also
      found between everyday functioning and the SIX-item 'friendship' and a negative
      correlation between duration of ACT and everyday functioning. A significant
      increase in number of inpatient hospital days and psychiatric outpatient visits
      also occurred. CONCLUSION: Clients with psychosis who need ACT may benefit from
      Flexible ACT through improved social functioning. Being involved in meaningful
      activities and supported by others are key aspects of recovering from mental
      illness and are enhanced by Flexible ACT.

PMID- 29373935
TI  - Pharmacokinetic drug evaluation of avibactam + ceftazidime for the treatment of
      hospital-acquired pneumonia.
AB  - INTRODUCTION: Ceftazidime-avibactam (CAZ-AVI) is a combination of a third
      generation cephalosporin and a non-beta-lactam, beta-lactamase inhibitor,
      recently approved for urinary tract infections and complicated abdominal
      infections. Moreover, it represents a treatment option for patients with hospital
      acquired pneumonia (HAP), especially when caused by multidrug-resistant (MDR)
      bacteria. Areas covered: The review focuses on the pharmacokinetics (PK) of CAZ
      AVI in HAP and on preclinical and clinical studies evaluating PK/pharmacodynamics
      (PD) in this field. Expert opinion: In vitro and in vivo data about PK/PD of CAZ
      AVI confirm that penetration of CAZ-AVI in the epithelial lining fluid (ELF)
      represents approximately 30% of the plasma concentrations. Clinical studies
      documented that CAZ-AVI 2000 mg/500 mg every 8 h is the optimal dose regimen to
      achieve the PK/PD target attainment in patients with HAP. Thus, CAZ-AVI could
      represent an option both to treat HAP caused by Gram-negative bacilli (GNB)
      displaying resistance to most of the antibiotics and to reduce the use of
      carbapenems, limiting the onset of resistance profiles among GNB. Additional
      information about specific patients populations, such as critically-ill subjects
      or pediatric patients, are needed for a more individualized use of CAZ-AVI.

PMID- 29373936
TI  - The moderating role of meaning in life in the relationship between perceived
      stress and diurnal cortisol.
AB  - Previous studies have suggested that meaning in life may buffer the negative
      effects of stress. This study is the first to investigate the moderating role of
      meaning in life in the relationship between the perception of stress and diurnal
      cortisol in two independent samples of healthy adults. In study 1 (n = 172, men =
      82, women = 90, age range = 21-55 years, mean age = 37.58 years), the results of
      moderated regression analyses revealed that there was a significant positive
      relationship between overall perceived stress in the past month and both diurnal
      cortisol levels (area-under-the-curve with respect to the ground; AUCg) and the
      diurnal cortisol slope (DCS) only in individuals with low levels of meaning in
      life conceptualized as the degree to which one engages in activities that are
      personally valued and important. In study 2 (n = 259, men = 125, women = 134, age
      range = 18-54 years, mean age = 29.06 years), we found a non-significant
      interaction term between meaning in life conceptualized as having goals and a
      sense of excitement regarding one's future and perception of stress in a model of
      both adjusted AUCg and DCS. The results were independent of age, sex, body mass
      index, education, and race. The results shed light on the importance and the
      complexity of the construct of meaning in life and offer a possible explanation
      for why some people who face stressors may be more vulnerable than others to
      developing stress-related health problems.

PMID- 29373937
TI  - Binaural model-based dynamic-range compression.
AB  - OBJECTIVE: Binaural cues such as interaural level differences (ILDs) are used to
      organise auditory perception and to segregate sound sources in complex acoustical
      environments. In bilaterally fitted hearing aids, dynamic-range compression
      operating independently at each ear potentially alters these ILDs, thus
      distorting binaural perception and sound source segregation. DESIGN: A binaurally
      linked model-based fast-acting dynamic compression algorithm designed to
      approximate the normal-hearing basilar membrane (BM) input-output function in
      hearing-impaired listeners is suggested. A multi-center evaluation in comparison
      with an alternative binaural and two bilateral fittings was performed to assess
      the effect of binaural synchronisation on (a) speech intelligibility and (b)
      perceived quality in realistic conditions. STUDY SAMPLE: 30 and 12 hearing
      impaired (HI) listeners were aided individually with the algorithms for both
      experimental parts, respectively. RESULTS: A small preference towards the
      proposed model-based algorithm in the direct quality comparison was found.
      However, no benefit of binaural-synchronisation regarding speech intelligibility
      was found, suggesting a dominant role of the better ear in all experimental
      conditions. CONCLUSION: The suggested binaural synchronisation of compression
      algorithms showed a limited effect on the tested outcome measures, however,
      linking could be situationally beneficial to preserve a natural binaural
      perception of the acoustical environment.

PMID- 29373938
TI  - Spread of carbapenem resistant Enterobacteriaceae at tertiary care cancer
      hospital in Egypt.

PMID- 29373939
TI  - Fish DNA barcoding around large marine infrastructure for improved biodiversity
      assessment and monitoring.
AB  - Accurate species-level identification is pivotal for environmental assessments
      and monitoring. The PERU LNG terminal is composed of large marine infrastructure
      located on the central coast of Peru. Since construction, taxonomically
      challenging species such as drum fishes (Sciaenidae) have been attracted to the
      new hard-bottom habitat. We conducted a DNA barcoding study to investigate fish
      diversity and constructed a DNA barcode reference library. We examined 56
      vouchered specimens and identified 24 unique species. Intra- and interspecific
      divergence estimates ranged between 0 and 0.64% and 11 and 35.5%, respectively.
      We assessed the efficiency of the reference library to identify 29 non-vouchered
      specimens. We had 82.5% efficiency by using both our reference library (n = 17)
      and GenBank (n = 24). We highlight the importance of implementing molecular
      barcoding for complementing biodiversity assessments in marine environments. This
      study represents a first step towards generating a comprehensive DNA barcode
      reference library for marine fishes in Peru.

PMID- 29373940
TI  - Zein nanoparticle as a novel BMP6 derived peptide carrier for enhanced osteogenic
      differentiation of C2C12 cells.
AB  - Zein nanoparticles as a carrier system for BMP6-derived peptide were prepared by
      liquid-liquid phase separation procedure and characterized with SEM, DLS, FTIR
      and thermogravimetric methods. After peptide encapsulation, nanoparticle size
      increased from 236.3 +/- 92.2 nm to 379.4 +/- 116.8 nm. The encapsulation
      efficiency of peptide was 72.6% and the release of peptide from Zein
      nanoparticles was partly sustained in trypsin containing phosphate buffered
      saline (pH 7.4) for up to 14 days. Peptide-loaded nanoparticles showed similar
      cell viability compared with blank ones. ALP activity of C2C12 cells treated with
      peptide-loaded nanoparticles (500 ug/mL) was evaluated 7, 14, 21 and 28 days
      after culture. In peptide-loaded nanoparticles, ALP activity was significantly
      higher (p < .05) compared with other groups at day 14. Alizarin Red S staining
      showed, C2C12 cells behind peptide-loaded nanoparticles had significantly (p <
      .05) higher calcium deposition at day 21. The results of RT-qPCR show that the
      BMP-6 peptide activated expression of RUNX2 as a transcription factor. In turn,
      RUNX2 regulates SPP1 and BGLAP gene expression, as osteogenic marker genes. The
      results confirm that the peptide-loaded Zein nanoparticles, as osteoinductive
      material, may be used to repair small area of bone defects, with low load
      bearing.

PMID- 29373941
TI  - Nutritional status and nutritional risk in patients with neuroendocrine tumors.
AB  - BACKGROUND: Malnutrition is frequent among patients with malignancies and
      associated with impaired function, reduced quality of life and increased
      mortality. Few data are available in patients with neuroendocrine tumors (NET) on
      nutritional status, nutritional risk, and nutrition impact symptoms (NIS). We
      aimed to assess nutritional status (NS) and risk, level of function and
      associations with NIS in NET patients. METHODS: In a cross-sectional study of NET
      patients, we measured body mass index (BMI) and handgrip strength (HGS) as
      markers of NS and muscle function assessed by HGS. The nutritional risk score
      (NRS) was determined by NRS-2002. NIS was assessed by the eating symptoms
      questionnaire (ESQ), and disease-related appetite questionnaire (DRAQ). RESULTS:
      We included 186 patients (51% women), median age 66 years. We observed low BMI
      (<20.5 kg/m2) in 12%, low HGS in 25%, and impaired level of function in 43% of
      the patients. About 38% were at nutritional risk, more frequent in patients with
      residual disease (45% versus 29%, p < .05). Both low HGS, impaired level of
      function and being at nutritional risk were associated with the NIS: Nausea,
      vomiting, stomach ache and dry mouth (p < .05) whereas poor appetite and early
      satiety were only associated with being at nutritional risk and having impaired
      level of function (p < .05, all). CONCLUSIONS: Almost 40% of NET patients were at
      nutritional risk; and 25% had impaired HGS associated with specific NIS that
      preclude food intake. We recommend that NET outpatients are screened with NRS
      2002 and that HGS and NIS are determined if NET patients need nutritional
      therapy.

PMID- 29373942
TI  - Determination of essential oils composition of blanket-leaf (Stachys byzantina C.
      Koch.) by microwave assisted extraction coupled to headspace single-drop
      microextraction.
AB  - The composition of essential oils from Stachys byzantina was studied by simple
      method based on gas chromatography-mass spectrophotometry (GC-MS) following
      microwave assisted headspace single-drop microextraction (MA-HS-SDME) method.
      Several parameters affecting MA-HS-SDME such as sample mass, solvent volume,
      extraction time, microwave power and the nature of extracting solvent were
      optimised. The MA-HS-SDME method was compared with traditional hydrodistillation
      (HD) method. Within the study elaborated, thirty-eight components were extracted
      and identified. Compared with HD, MA-HS-SDME is an easy, rapid and efficient
      method for the analysis of essential oils in S. byzantina.

PMID- 29373943
TI  - Twelve tips for constructing a multiple mini-interview.
AB  - Health professions the world over value various competencies in their
      practitioners that are not easily captured by academic measures of performance.
      As a result, many programs have begun using multiple mini-interviews (MMIs) to
      facilitate the selection of candidates who are most likely to demonstrate and
      further develop such qualities. In this twelve-tips article, the authors offer
      evidence- and experience-based advice regarding how to construct an MMI that is
      fit for purpose. The tips are provided chronologically, offering guidance
      regarding how one might conceptualize their goals for creating an MMI, how to
      establish a database of stations that are context appropriate, and how to prepare
      both candidates and examiners for their task. While MMIs have been shown to have
      utility in many instances, the authors urge caution against over-generalization
      by stressing the importance of post-MMI considerations including data monitoring
      and integration between one's admissions philosophy and one's curricular efforts.

PMID- 29373944
TI  - Using gold nanoparticles in diagnosis and treatment of melanoma cancer.
AB  - Several studies have been devoted to clear functionalization of gold
      nanoparticles (AuNPs) in different fields such as cellular and molecular biology,
      microbiology, immunology and physiology. In line with the high diagnostic value
      of AuNPs, its therapeutic application has been intensively developed in tumour
      therapy, in recent years. One of the best clinical applications of AuNPs is its
      use in targeted delivery of anti-cancer drugs. Recent studies have focused on the
      application of AuNPs to treat melanoma - a malignant neoplasm sourced from
      melanocytes skin cells - with poor prognosis in advanced stages. Furthermore,
      early diagnosis can be successfully achieved through utilizing this technique
      even at early stages with localized distribution. Herein, this study details the
      previous researches focusing on the use of AuNPs as a novel diagnostic and
      therapeutic option in management of melanoma.

PMID- 29373945
TI  - Perfusion Enhances Hypertrophic Chondrocyte Matrix Deposition, But Not the Bone
      Formation.
AB  - Perfusion bioreactors have been an effective tool in bone tissue engineering.
      Improved nutrient delivery and the application of shear forces have stimulated
      osteoblast differentiation and matrix production, allowing for generation of
      large, clinically sized constructs. Differentiation of hypertrophic chondrocytes
      has been considered an alternative strategy for bone tissue engineering. We
      studied the effects of perfusion on hypertrophic chondrocyte differentiation,
      matrix production, and subsequent bone formation. Hypertrophic constructs were
      created by differentiation in chondrogenic medium (2 weeks) and maturation in
      hypertrophic medium (3 weeks). Bioreactors were customized to study a range of
      flow rates (0-1200 MUm/s). During chondrogenic differentiation, increased flow
      rates correlated with cartilage matrix deposition and the presence of collagen
      type X. During induced hypertrophic maturation, increased flow rates correlated
      with bone template deposition and the increased secretion of chondroprotective
      cytokines. Following an 8-week implantation into the critical-size femoral defect
      in nude rats, nonperfused constructs displayed larger bone volume, more compact
      mineralized matrix, and better integration with the adjacent native bone.
      Therefore, although medium perfusion stimulated the formation of bone template in
      vitro, it failed to enhance bone regeneration in vivo. However, the promising
      results of the less developed template in the critical-sized defect warrant
      further investigation, beyond interstitial flow, into the specific environment
      needed to optimize hypertrophic chondrocyte-based constructs for bone repair.

PMID- 29373946
TI  - Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic
      Spinal Cord Injury.
AB  - There are no effective therapies available currently to ameliorate loss of
      function for patients with spinal cord injuries (SCIs). In addition, proposed
      treatments that demonstrated functional recovery in animal models of acute SCI
      have failed almost invariably when applied to chronic injury models. Glial scar
      formation in chronic injury is a likely contributor to limitation on
      regeneration. We have removed existing scar tissue in chronically contused rat
      spinal cord using a rose Bengal-based photo ablation approach. In this study, we
      compared two chemically modified rose bengal derivatives to unmodified rose
      bengal, both confirming and expanding on our previously published report. Rats
      were treated with unmodified rose bengal (RB1) or rose bengal modified with
      hydrocarbon (RB2) or polyethylene glycol (RB3), to determine the effects on scar
      components and spared tissue post-treatment. Our results showed that RB1 was more
      efficacious than RB2, while still maintaining minimal collateral effects on
      spared tissue. RB3 was not taken up by the cells, likely because of its size, and
      therefore had no effect. Treatment with RB1 also resulted in an increase in
      serotonin eight days post-treatment in chronically injured spinal cords. Thus, we
      suggest that unmodified rose Bengal is a potent candidate agent for the
      development of a therapeutic strategy for scar ablation in chronic SCI.

PMID- 29373948
TI  - Traumatic Brain Injury Disrupts Pain Signaling in the Brainstem and Spinal Cord.
AB  - Chronic pain is a common consequence of traumatic brain injury (TBI) that can
      increase the suffering of a patient and pose a significant challenge to
      rehabilitative efforts. Unfortunately, the mechanisms linking TBI to pain are
      poorly understood, and specific treatments for TBI-related pain are still
      lacking. Our laboratory has shown that TBI causes pain sensitization in areas
      distant to the site of primary injury, and that changes in spinal gene expression
      may underlie this sensitization. The aim of this study was to examine the roles
      that pain modulatory pathways descending from the brainstem play in pain after
      TBI. Deficiencies in one type of descending inhibition, diffuse noxious
      inhibitory control (DNIC), have been suggested to be responsible for the
      development of chronic pain by allowing excess and uncontrolled afferent
      nociceptive inputs. Here we expand our knowledge of pain after TBI in two ways:
      (1) by outlining the neuropathology in pain-related centers of the brain and
      spinal cord involved in DNIC using the rat lateral fluid percussion (LFP) model
      of TBI, and (2) by evaluating the effects of a potent histone acetyl transferase
      inhibitor, anacardic acid (AA), on LFP-induced pain behaviors and neuropathology
      when administered for several days after TBI. The results revealed that TBI
      induces transient mechanical allodynia and a chronic persistent loss of DNIC.
      Further, while short-term AA treatment can block acute nociceptive sensitization
      and some early neuropathological changes, this treatment neither prevented the
      loss of DNIC nor did it alter long-term neuropathological changes in the brain or
      spinal cord.

PMID- 29373947
TI  - Reduced Functional Connectivity in Adults with Persistent Post-Concussion
      Symptoms: A Functional Near-Infrared Spectroscopy Study.
AB  - Concussion, or mild traumatic brain injury (mTBI), accounts for ~80% of all TBIs
      across North America. The majority of mTBI patients recover within days to weeks;
      however, 14-36% of the time, acute mTBI symptoms persist for months or even years
      and develop into persistent post-concussion symptoms (PPCS). There is a need to
      find biomarkers in patients with PPCS, to improve prognostic ability and to
      provide insight into the pathophysiology underlying chronic symptoms. Recent
      research has pointed toward impaired network integrity and cortical communication
      as a biomarker. In this study we investigated functional near-infrared
      spectroscopy (fNIRS) as a technique to assess cortical communication deficits in
      adults with PPCS. Specifically, we aimed to identify cortical communication
      patterns in prefrontal and motor areas during rest and task, in adult patients
      with persistent symptoms. We found that (1) the PPCS group showed reduced
      connectivity compared with healthy controls, (2) increased symptom severity
      correlated with reduced coherence, and (3) connectivity differences were best
      distinguishable during task and in particular during the working memory task (n
      back task) in the right and left dorsolateral prefrontal cortex (DLPFC). These
      data show that reduced brain communication may be associated with the
      pathophysiology of mTBI and that fNIRS, with a relatively simple acquisition
      paradigm, may provide a useful biomarker of this injury.

PMID- 29373949
TI  - Effect of Tumor Size on Risk of Metastatic Disease and Survival for Thyroid
      Cancer: Implications for Biopsy Guidelines.
AB  - BACKGROUND: In many risk-stratification systems, the decision to biopsy thyroid
      nodules is determined by their sonographic features and size. Nevertheless, even
      low-suspicion nodules are often biopsied at small size thresholds because it is
      assumed that larger malignant nodules are associated with poorer outcomes. The
      aim of this study was to quantify the effect of thyroid cancer tumor size on
      survival and risk of T4 stage, nodal disease, and distant metastases. METHODS:
      The Surveillance, Epidemiology, and End Results 18 database was queried to obtain
      tumor size, staging information, and survival data for cases of differentiated
      thyroid cancer (DTC) and non-DTC reported between 2004 and 2014. Observed
      probabilities of tumor extent at diagnosis, including regional nodal disease and
      distant metastases, as a function of size and tumor histology were estimated for
      thyroid cancers measuring between 1 and 150 mm. A multivariate Cox regression
      model was used to describe all-cause mortality as a function of patient and tumor
      characteristics, and the functional dependence of mortality on size was computed.
      RESULTS: A total of 112,128 patients were analyzed, with 67% having thyroid
      cancers >=1 cm, and 29% >= 2.5 cm. For DTC tumors <4 cm, the risk of local
      invasion, nodal metastases, or distant metastases was low, and there was no size
      threshold associated with a sharp rise in adverse outcomes. For DTC tumors <4 cm,
      the probability of distant metastases was <3%. Older age, male sex, non-DTC
      histology, T4 stage, and regional and distant metastatic disease increased the
      all-cause mortality rate. Tumor size did not increase the mortality rate above
      baseline until tumors were >2.5 cm. CONCLUSION: Increasing tumor size does not
      affect survival until a threshold of 2.5 cm. Since the dimension of nodules on
      ultrasound has been shown to be larger than their size at gross pathology, these
      findings suggest that recommended size thresholds to biopsy low-suspicion thyroid
      nodules can be increased.

PMID- 29373950
TI  - Compassion, medical humanities and medical education.
AB  - Compassion is central to person centred clinical care. Medical Humanities have
      developed both as an academic discipline and as a resource for education over the
      past 30 years. The article will discuss what compassion is in a clinical context,
      and explore whether compassionate clinical practice can be enhanced by using the
      humanities in medical education in primary care.

PMID- 29373953
TI  - Rice nucleosome patterns undergo remodeling coincident with stress-induced gene
      expression.
AB  - BACKGROUND: Formation of nucleosomes along eukaryotic DNA has an impact on
      transcription. Major transcriptional changes occur in response to low external
      phosphate (Pi) in plants, but the involvement of chromatin-level mechanisms in Pi
      starvation responses have not been investigated. RESULTS: We mapped nucleosomes
      along with transcriptional changes after 24-h of Pi starvation in rice (Oryza
      sativa) by deep sequencing of micrococcal nuclease digested chromatin and
      ribosome-depleted RNA. We demonstrated that nucleosome patterns at rice genes
      were affected by both cis- and trans-determinants, including GC content and
      transcription. Also, categorizing rice genes by nucleosome patterns across the
      transcription start site (TSS) revealed nucleosome patterns that correlated with
      distinct functional categories of genes. We further demonstrated that Pi
      starvation resulted in numerous dynamic nucleosomes, which were enhanced at genes
      differentially expressed in response to Pi starvation. CONCLUSIONS: We
      demonstrate that rice nucleosome patterns are suggestive of gene functions, and
      reveal a link between chromatin remodeling and transcriptional changes in
      response to deficiency of a major macronutrient. Our findings help to enhance the
      understanding towards eukaryotic gene regulation at the chromatin level.

PMID- 29373954
TI  - Genomic selection models for directional dominance: an example for litter size in
      pigs.
AB  - BACKGROUND: The quantitative genetics theory argues that inbreeding depression
      and heterosis are founded on the existence of directional dominance. However,
      most procedures for genomic selection that have included dominance effects
      assumed prior symmetrical distributions. To address this, two alternatives can be
      considered: (1) assume the mean of dominance effects different from zero, and (2)
      use skewed distributions for the regularization of dominance effects. The aim of
      this study was to compare these approaches using two pig datasets and to confirm
      the presence of directional dominance. RESULTS: Four alternative models were
      implemented in two datasets of pig litter size that consisted of 13,449 and
      11,581 records from 3631 and 2612 sows genotyped with the Illumina PorcineSNP60
      BeadChip. The models evaluated included (1) a model that does not consider
      directional dominance (Model SN), (2) a model with a covariate b for the average
      individual homozygosity (Model SC), (3) a model with a parameter lambda that
      reflects asymmetry in the context of skewed Gaussian distributions (Model AN),
      and (4) a model that includes both b and lambda (Model Full). The results of the
      analysis showed that posterior probabilities of a negative b or a positive lambda
      under Models SC and AN were higher than 0.99, which indicate positive directional
      dominance. This was confirmed with the predictions of inbreeding depression under
      Models Full, SC and AN, that were higher than in the SN Model. In spite of
      differences in posterior estimates of variance components between models,
      comparison of models based on LogCPO and DIC indicated that Model SC provided the
      best fit for the two datasets analyzed. CONCLUSIONS: Our results confirmed the
      presence of positive directional dominance for pig litter size and suggested that
      it should be taken into account when dominance effects are included in genomic
      evaluation procedures. The consequences of ignoring directional dominance may
      affect predictions of breeding values and can lead to biased prediction of
      inbreeding depression and performance of potential mates. A model that assumes
      Gaussian dominance effects that are centered on a non-zero mean is recommended,
      at least for datasets with similar features to those analyzed here.

PMID- 29373955
TI  - SLALOM, a flexible method for the identification and statistical analysis of
      overlapping continuous sequence elements in sequence- and time-series data.
AB  - BACKGROUND: Protein or nucleic acid sequences contain a multitude of associated
      annotations representing continuous sequence elements (CSEs). Comparing these
      CSEs is needed, whenever we want to match identical annotations or integrate
      distinctive ones. Currently, there is no ready-to-use software available that
      provides comprehensive statistical readout for comparing two annotations of the
      same type with each other, which can be adapted to the application logic of the
      scientific question. RESULTS: We have developed a method, SLALOM (for StatisticaL
      Analysis of Locus Overlap Method), to perform comparative analysis of sequence
      annotations in a highly flexible way. SLALOM implements six major operation modes
      and a number of additional options that can answer a variety of statistical
      questions about a pair of input annotations of a given sequence collection. We
      demonstrate the results of SLALOM on three different examples from biology and
      economics and compare our method to already existing software. We discuss the
      importance of carefully choosing the application logic to address specific
      scientific questions. CONCLUSION: SLALOM is a highly versatile, command-line
      based method for comparing annotations in a collection of sequences, with a
      statistical read-out for performance evaluation and benchmarking of predictors
      and gene annotation pipelines. Abstraction from sequence content even allows
      SLALOM to compare other kinds of positional data including, for example, data
      coming from time series.

PMID- 29373956
TI  - Age independency of mobility decrease assessed using the Locomotive Syndrome Risk
      Test in elderly with disability: a cross-sectional study.
AB  - BACKGROUND: Mobility decrease is reportedly age-dependent in community dwelling
      elderly, and a major factor of disability in the geriatric population. The
      purpose of this study is to examine whether mobility decrease, as assessed using
      a set of tests, is similarly age-dependent in elderly adults who already have
      disability. METHODS: One hundred thirty-five community-dwelling elderly (54 men,
      81 women) with disability and 1469 independent community dwellers (1009 men, 460
      women) were analyzed. Disability was defined having a certified need for care
      under the long-term care insurance system in Japan. Lower extremity mobility
      decrease was quantified using the Locomotive Syndrome Risk Test, which comprises
      the two-step test, stand-up test, and 25-Question Geriatric Locomotive Function
      Scale (GLFS-25). RESULTS: Multivariable regression analyses indicated no age
      related decrease in the three test scores among elderly with disability, whereas
      these scores all decreased with age among independent community dwellers. All the
      test scores decreased as care level increased. CONCLUSIONS: Mobility decrease
      among elderly adults with disability is unrelated to age. However, the severity
      of care level is associated with mobility decrease.

PMID- 29373957
TI  - Patterns of variation in cis-regulatory regions: examining evidence of purifying
      selection.
AB  - BACKGROUND: With only 2 % of the human genome consisting of protein coding genes,
      functionality across the rest of the genome has been the subject of much debate.
      This has gained further impetus in recent years due to a rapidly growing
      catalogue of genomic elements, based primarily on biochemical signatures (e.g.
      the ENCODE project). While the assessment of functionality is a complex task, the
      presence of selection acting on a genomic region is a strong indicator of
      importance. In this study, we apply population genetic methods to investigate
      signals overlaying several classes of regulatory elements. RESULTS: We
      disentangle signals of purifying selection acting directly on regulatory elements
      from the confounding factors of demography and purifying selection linked to e.g.
      nearby protein coding regions. We confirm the importance of regulatory regions
      proximal to coding sequence, while also finding differential levels of selection
      at distal regions. We note differences in purifying selection among transcription
      factor families. Signals of constraint at some genomic classes were also strongly
      dependent on their physical location relative to coding sequence. In addition,
      levels of selection efficacy across genomic classes differed between African and
      non-African populations. CONCLUSIONS: In order to assign a valid signal of
      selection to a particular class of genomic sequence, we show that it is crucial
      to isolate the signal by accounting for the effects of demography and linked
      purifying selection. Our study highlights the intricate interplay of factors
      affecting signals of selection on functional elements.

PMID- 29373958
TI  - Determinants of HIV infection among adolescent girls and young women aged 15-24
      years in South Africa: a 2012 population-based national household survey.
AB  - BACKGROUND: South Africa is making tremendous progress in the fight against HIV,
      however, adolescent girls and young women aged 15-24 years (AGYW) remain at
      higher risk of new HIV infections. This paper investigates socio-demographic and
      behavioural determinants of HIV infection among AGYW in South Africa. METHODS: A
      secondary data analysis was undertaken based on the 2012 population-based
      nationally representative multi-stage stratified cluster random household sample.
      Multivariate stepwise backward and forward regression modelling was used to
      determine factors independently associated with HIV prevalence. RESULTS: Out of
      3092 interviewed and tested AGYW 11.4% were HIV positive. Overall HIV prevalence
      was significantly higher among young women (17.4%) compared to adolescent girls
      (5.6%). In the AGYW model increased risk of HIV infection was associated with
      being young women aged 20-24 years (OR = 2.30, p = 0.006), and condom use at last
      sex (OR = 1.91, p = 0.010), and decreased likelihood was associated with other
      race groups (OR = 0.06, p < 0.001), sexual partner within 5 years of age (OR =
      0.53, p = 0.012), tertiary level education (OR = 0.11, p = 0.002), low risk
      alcohol use (OR = 0.19, p = 0.022) and having one sexual partner (OR = 0.43, p =
      0.028). In the adolescent girls model decreased risk of HIV infection was
      associated with other race groups (OR = 0.01, p < 0.001), being married (OR =
      0.07), p = 0.016], and living in less poor household (OR = 0.08, p = 0.002). In
      the young women's models increased risk of HIV infection was associated with
      condom use at last sex (OR = 2.09, p = 0.013), and decreased likelihood was
      associated with other race groups (OR = 0.17, p < 0.001), one sexual partner (OR
      = 0.6, p = 0.014), low risk alcohol use (OR = 0.17, p < 0.001), having a sexual
      partner within 5 years of age (OR = 0.29, p = 0.022), and having tertiary
      education (OR = 0.29, p = 0.022). CONCLUSION: These findings support the need to
      design combination prevention interventions which simultaneously address socio
      economic drivers of the HIV epidemic, promote education, equity and access to
      schooling, and target age-disparate partnerships, inconsistent condom use and
      risky alcohol consumption.

PMID- 29373959
TI  - Sequential decitabine and carboplatin treatment increases the DNA repair protein
      XPC, increases apoptosis and decreases proliferation in melanoma.
AB  - BACKGROUND: Melanoma has two key features, an over-representation of UV-induced
      mutations and resistance to DNA damaging chemotherapy agents. Both of these
      features may result from dysfunction of the nucleotide excision repair pathway,
      in particular the DNA damage detection branch, global genome repair (GGR). The
      key GGR component XPC does not respond to DNA damage in melanoma, the cause of
      this lack of response has not been investigated. In this study, we investigated
      the role of methylation in reduced XPC in melanoma. METHODS: To reduce
      methylation and induce DNA-damage, melanoma cell lines were treated with
      decitabine and carboplatin, individually and sequentially. Global DNA methylation
      levels, XPC mRNA and protein expression and methylation of the XPC promoter were
      examined. Apoptosis, cell proliferation and senescence were also quantified. XPC
      siRNA was used to determine that the responses seen were reliant on XPC
      induction. RESULTS: Treatment with high-dose decitabine resulted in global
      demethylation, including the the shores of the XPC CpG island and significantly
      increased XPC mRNA expression. Lower, clinically relevant dose of decitabine also
      resulted in global demethylation including the CpG island shores and induced XPC
      in 50% of cell lines. Decitabine followed by DNA-damaging carboplatin treatment
      led to significantly higher XPC expression in 75% of melanoma cell lines tested.
      Combined sequential treatment also resulted in a greater apoptotic response in
      75% of cell lines compared to carboplatin alone, and significantly slowed cell
      proliferation, with some melanoma cell lines going into senescence. Inhibiting
      the increased XPC using siRNA had a small but significant negative effect,
      indicating that XPC plays a partial role in the response to sequential decitabine
      and carboplatin. CONCLUSIONS: Demethylation using decitabine increased XPC and
      apoptosis after sequential carboplatin. These results confirm that sequential
      decitabine and carboplatin requires further investigation as a combination
      treatment for melanoma.

PMID- 29373960
TI  - Gastric bacterial Flora in patients Harbouring Helicobacter pylori with or
      without chronic dyspepsia: analysis with matrix-assisted laser desorption
      ionization time-of-flight mass spectroscopy.
AB  - BACKGROUND: The gastric microbiota has recently been implicated in the causation
      of organic/structural gastroduodenal diseases (gastric and duodenal ulcers,
      gastric cancer) in patients with Helicobacter pylori (H. pylori) infection. We
      aimed to ascertain, in patients harbouring H. pylori, the role of the gastric
      microbiota in the causation of symptoms (chronic dyspepsia) in the absence of
      organic disease. METHODS: Seventy-four gastric biopsy samples obtained at
      endoscopy from patients with (n = 21) or without (n = 53) chronic dyspepsia, and
      that tested positive by the bedside rapid urease test for H. pylori infection,
      were cultured for detection of H. pylori and non-H. pylori organisms. The
      cultured organisms were identified by matrix-assisted laser desorption ionization
      time-of-flight mass spectroscopy (MALDI-TOF MS). RESULTS: A total of 106 non-H.
      pylori isolates were obtained from 74 patients' samples. This included 33
      isolates (median 2, range 1-2 per patient) from dyspeptic and 73 (median 2, range
      1-2 per patient) from non-dyspeptic patients. These were identified from the
      Bruker Biotyper 2 database as Staphylococcus spp., Streptococcus spp.,
      Lactobacillus spp., Micrococcus spp., Enterococcus spp., Pseudomonas spp.,
      Escherichia spp., Klebsiella spp. and Bacillus spp., Staphylococcus and
      Lactobacillus were identified significantly more commonly in dyspeptics and
      Streptococcus, Pseudomonas, Escherichia coli and Klebsiella pneumoniae in non
      dyspeptics. All identified organisms belonged to the phyla Firmicutes and
      Proteobacteria. CONCLUSIONS: There is a qualitative difference in the gastric
      microbial spectrum between patients harbouring H. pylori with and without chronic
      dyspepsia. Whether these organisms have an independent role in the development or
      prevention of dyspepsia or act in concurrence with H. pylori needs study.

PMID- 29373961
TI  - Forehead or ear temperature measurement cannot replace rectal measurements,
      except for screening purposes.
AB  - BACKGROUND: Measuring rectal temperature in children is the gold standard, but
      ear or forehead measures are less traumatic and faster. The quality of non
      invasive devices has improved but concerns remain whether they are reliable
      enough to substitute rectal thermometers. The aim was to evaluate in a real-life
      children population whether the forehead or ear temperature measurements could be
      used in screening to detect fever and if the agreement with the rectal
      temperature for different age groups is acceptable for clinical use. METHODS:
      Cross-sectional clinical study comparing temporal and tympanic temperatures to
      rectal temperature in 0-18-year-old children. The ear thermometer was a Pro 4000
      Thermoscan, the temporal Exergen TAT. Rectal temperature >= 38.0  degrees C was
      defined as fever. RESULTS: Among 995 children, 39% had a fever. The ear
      thermometer had a significantly greater ability to detect fever than the temporal
      thermometer (AUC 0.972; 95% CI: 0.963-0.981 versus AUC 0.931; 95% CI: 0.915
      0.947, p < 0.0001). Both devices had the lowest sensitivity in the youngest and
      oldest children, and only the ear thermometer reached a sensitivity above 90% in
      the 0.5-5-year age group. The Bland-Altman analysis showed that the 95% limits of
      agreement for the temporal thermometer was between - 1.2 to + 1.5  degrees C and
      for the ear thermometer between - 0.97 to + 1.07  degrees C. CONCLUSIONS: Based
      on a large sample of children, the temporal measurement of temperature is not
      currently recommendable, but with the technology used in this study the ear
      measurement proved useful for screening purposes, especially among children aged
      6 months to 5 years. For the exact measurement of temperature, the rectal method
      is still recommended.

PMID- 29373962
TI  - Process, structural, and outcome quality indicators of nutritional care in
      nursing homes: a systematic review.
AB  - BACKGROUND: The quality of nursing homes (NHs) has attracted a lot of interest in
      recent years and is one of the most challenging issues for policy-makers.
      Nutritional care should be considered an important variable to be measured from
      the perspective of quality management. The aim of this systematic review is to
      describe the use of structural, process, and outcome indicators of nutritional
      care in NHs and the relationship among them. METHODS: The literature search was
      carried out in Pubmed, Embase, Scopus, and Web of Science. A temporal filter was
      applied in order to select papers published in the last 10 years. All types of
      studies were included, with the exception of reviews, conference proceedings,
      editorials, and letters to the editor. Papers published in languages other than
      English, Italian, and Spanish were excluded. RESULTS: From the database search,
      1063 potentially relevant studies were obtained. Of these, 19 full-text articles
      were considered eligible for the final synthesis. Most of the studies adopted an
      observational cross-sectional design. They generally assessed the quality of
      nutritional care using several indicators, usually including a mixture of many
      different structural, process, and outcome indicators. Only one of the 19 studies
      described the quality of care by comparing the results with the threshold values.
      Nine papers assessed the relationship between indicators and six of them
      described some significant associations-in the NHs that have a policy related to
      nutritional risk assessment or a suitable scale to weigh the residents, the
      prevalence or risk of malnutrition is lower. Finally, only four papers of these
      nine included risk adjustment. This could limit the comparability of the results.
      CONCLUSION: Our findings show that a consensus must be reached for defining a set
      of indicators and standards to improve quality in NHs. Establishing the
      relationship between structural, process, and outcome indicators is a challenge.
      There are grounds for investigating this theme by means of prospective
      longitudinal studies that take the risk adjustment into account.

PMID- 29373963
TI  - The presentation of a short adapted questionnaire to measure asthma knowledge of
      parents.
AB  - BACKGROUND: The aim of this study is to establish asthma knowledge of parents of
      children (0-18 years) with asthma at the outpatient clinic. METHODS: A translated
      and adapted a 21 item Likert type 5 point scale questionnaire (Cronbach's alpha
      coefficient 0.73) was completed by 291 parents of children with asthma. Total
      asthma knowledge scores were associated with demographic and psychosocial
      variables. RESULTS: Factor analysis resulted in a new reduced 10 item
      questionnaire (Cronbach's alpha-coefficient 0.72). Higher educational level of
      parents was associated with better asthma knowledge (p < 0.008 and p < 0.003).
      Parents showed more knowledge (p < 0.001) on non-medication questions. Asthma
      knowledge of the parent did not correlate with child age, gender, duration of
      airway problems, time since diagnosis or severity of asthma. CONCLUSIONS:
      Education of parents concerning the working mechanism, indications and use of
      asthma medications are an essential part of asthma education. Asthma education
      should be repeated frequently to parents of children with long-term airway
      problems or diagnosed asthma. Special attention must be paid to parents with only
      high school education or less.

PMID- 29373964
TI  - Palliative and end-of-life care research in Scotland 2006-2015: a systematic
      scoping review.
AB  - BACKGROUND: The Scottish Government set out its 5-year vision to improve
      palliative care in its Strategic Framework for Action 2016-2021. This includes a
      commitment to strengthening research and evidence based knowledge exchange across
      Scotland. A comprehensive scoping review of Scottish palliative care research was
      considered an important first step. The aim of the review was to quantify and map
      palliative care research in Scotland over the ten-year period preceding the new
      strategy (2006-15). METHODS: A systematic scoping review was undertaken.
      Palliative care research involving at least one co-author from a Scottish
      institution was eligible for inclusion. Five databases were searched with
      relevant MeSH terms and keywords; additional papers authored by members of the
      Scottish Palliative and End of Life Care Research Forum were added. RESULTS: In
      total, 1919 papers were screened, 496 underwent full text review and 308 were
      retained in the final set. 73% were descriptive studies and 10% were
      interventions or feasibility studies. The top three areas of research focus were
      services and settings; experiences and/or needs; and physical symptoms. 58 papers
      were concerned with palliative care for people with conditions other than cancer 
      nearly one fifth of all papers published. Few studies focused on ehealth, health
      economics, out-of-hours and public health. Nearly half of all papers described
      unfunded research or did not acknowledge a funder (46%). CONCLUSIONS: There was a
      steady increase in Scottish palliative care research during the decade under
      review. Research output was strong compared with that reported in an earlier
      Scottish review (1990-2005) and a similar review of Irish palliative care
      research (2002-2012). A large amount of descriptive evidence exists on living and
      dying with chronic progressive illness in Scotland; intervention studies now need
      to be prioritised. Areas highlighted for future research include palliative
      interventions for people with non-malignant illness and multi-morbidity; physical
      and psychological symptom assessment and management; interventions to support
      carers; and bereavement support. Knowledge exchange activities are required to
      disseminate research findings to research users and a follow-up review to examine
      future research progress is recommended.

PMID- 29373965
TI  - Empiric antibiotic therapy in urinary tract infection in patients with risk
      factors for antibiotic resistance in a German emergency department.
AB  - BACKGROUND: The aim of this study was to identify clinical risk factors for
      antimicrobial resistances and multidrug resistance (MDR) in urinary tract
      infections (UTI) in an emergency department in order to improve empirical
      therapy. METHODS: UTI cases from an emergency department (ED) during January 2013
      and June 2015 were analyzed. Differences between patients with and without
      resistances towards Ciprofloxacin, Piperacillin with Tazobactam (Pip/taz),
      Gentamicin, Cefuroxime, Cefpodoxime and Ceftazidime were analyzed with Fisher's
      exact tests. Results were used to identify risk factors with logistic regression
      modelling. Susceptibility rates were analyzed in relation to risk factors.
      RESULTS: One hundred thirty-seven of four hundred sixty-nine patients who met the
      criteria of UTI had a positive urine culture. An MDR pathogen was found in 36.5%
      of these. Overall susceptibility was less than 85% for standard antimicrobial
      agents. Logistic regression identified residence in nursing homes, male gender,
      hospitalization within the last 30 days, renal transplantation, antibiotic
      treatment within the last 30 days, indwelling urinary catheter and recurrent UTI
      as risk factors for MDR or any of these resistances. For patients with no risk
      factors Ciprofloxacin had 90%, Pip/taz 88%, Gentamicin 95%, Cefuroxime 98%,
      Cefpodoxime 98% and Ceftazidime 100% susceptibility. For patients with 1 risk
      factor Ciprofloxacin had 80%, Pip/taz 80%, Gentamicin 88%, Cefuroxime 78%,
      Cefpodoxime 78% and Ceftazidime 83% susceptibility. For 2 or more risk factors
      Ciprofloxacin drops its susceptibility to 52%, Cefuroxime to 54% and Cefpodoxime
      to 61%. Pip/taz, Gentamicin and Ceftazidime remain at 75% and 77%, respectively.
      CONCLUSIONS: We identified several risk factors for resistances and MDR in UTI.
      Susceptibility towards antimicrobials depends on these risk factors. With no risk
      factor cephalosporins seem to be the best choice for empiric therapy, but in
      patients with risk factors the beta-lactam penicillin Piperacillin with
      Tazobactam is an equal or better choice compared to fluoroquinolones,
      cephalosporins or gentamicin. This study highlights the importance of monitoring
      local resistance rates and its risk factors in order to improve empiric therapy
      in a local environment.

PMID- 29373966
TI  - Microeconomic institutions and personnel economics for health care delivery: a
      formal exploration of what matters to health workers in Rwanda.
AB  - BACKGROUND: Most developing countries face important challenges regarding the
      quality of health care, and there is a growing consensus that health workers play
      a key role in this process. Our understanding as to what are the key
      institutional challenges in human resources, and their underlying driving forces,
      is more limited. A conceptual framework that structures existing insights and
      provides concrete directions for policymaking is also missing. METHODS: To gain a
      bottom-up perspective, we gather qualitative data through semi-structured
      interviews with different levels of health workers and users of health services
      in rural and urban Rwanda. We conducted discussions with 48 health workers and 25
      users of health services in nine different groups in 2005. We maximized within
      group heterogeneity by selecting participants using specific criteria that affect
      health worker performance and career choice. The discussion were analysed
      electronically, to identify key themes and insights, and are documented with a
      descriptive quantitative analysis relating to the associations between
      quotations. The findings from this research are then revisited 10 years later
      making use of detailed follow-up studies that have been carried out since then.
      RESULTS: The original discussions identified both key challenges in human
      resources for health and driving forces of these challenges, as well as possible
      solutions. Two sets of issues were highlighted: those related to the size and
      distribution of the workforce and those related to health workers' on-the-job
      performance. Among the latter, four categories were identified: health workers'
      poor attitudes towards patients, absenteeism, corruption and embezzlement and
      lack of medical skills among some categories of health workers. The discussion
      suggest that four components constitute the deeper causal factors, which are,
      ranked in order of ease of malleability, incentives, monitoring arrangements,
      professional and workplace norms and intrinsic motivation. Three institutional
      innovations are identified that aim at improving performance: performance pay,
      community health workers and increased attention to training of health workers.
      Revisiting the findings from this primary research making use of later in-depth
      studies, the analysis demonstrates their continued relevance and usefulness. We
      discuss how the different factors affect the quality of care by impacting on
      health worker performance and labour market choices, making use of insights from
      economics and development studies on the role of institutions. CONCLUSION: The
      study results indicate that health care quality to an important degree depends on
      four institutional factors at the microlevel that strongly impact on health
      workers' performance and career choice, and which deserve more attention in
      applied research and policy reform. The analysis also helps to identify ways
      forwards, which fit well with the Ministry's most recent strategic plan.

PMID- 29373967
TI  - Personality dimensions emerging during adolescence and young adulthood are
      underpinned by a single latent trait indexing impairment in social functioning.
AB  - BACKGROUND: Personality with stable behavioural traits emerges in the adolescent
      and young adult years. Models of putatively distinct, but correlated, personality
      traits have been developed to describe behavioural styles including schizotypal,
      narcissistic, callous-unemotional, negative emotionality, antisocial and
      impulsivity traits. These traits have influenced the classification of their
      related personality disorders. We tested if a bifactor model fits the data better
      than correlated-factor and orthogonal-factor models and subsequently validated
      the obtained factors with mental health measures and treatment history. METHOD: A
      set of self-report questionnaires measuring the above traits together with
      measures of mental health and service use were collected from a volunteer
      community sample of adolescents and young adults aged 14 to 25 years (N = 2443).
      RESULTS: The bifactor model with one general and four specific factors emerged in
      exploratory analysis, which fit data better than models with correlated or
      orthogonal factors. The general factor showed high reliability and validity.
      CONCLUSIONS: The findings suggest that a selected range of putatively distinct
      personality traits is underpinned by a general latent personality trait that may
      be interpreted as a severity factor, with higher scores indexing more impairment
      in social functioning. The results are in line with ICD-11, which suggest an
      explicit link between personality disorders and compromised interpersonal or
      social function. The obtained general factor was akin to the overarching
      dimension of personality functioning (describing one's relation to the self and
      others) proposed by DSM-5 Section III.

PMID- 29373968
TI  - Frail-VIG index: a concise frailty evaluation tool for rapid geriatric
      assessment.
AB  - BACKGROUND: Demographic changes have led to an increase in the number of elderly
      frail persons and, consequently, systematic geriatric assessment is more
      important than ever. Frailty Indexes (FI) may be particularly useful to
      discriminate between various degrees of frailty but are not routinely assessed
      due, at least in part, to the large number of deficits assessed (from 30 to 70).
      Therefore, we have developed a new, more concise FI for rapid geriatric
      assessment (RGA)-the Frail-VIG index ("VIG" is the Spanish/Catalan abbreviation
      for Comprehensive Geriatric Assessment), which contains 22 simple questions that
      assess 25 different deficits. Here we describe this FI and report its ability to
      predict mortality at 24 months. METHODS: Prospective, observational, longitudinal
      study of geriatric patients followed for 24 months or until death. The study
      participants were patients (n = 590) admitted to the Acute Geriatric Unit at the
      at the University Hospital of Vic (Barcelona) during the year 2014. Participants
      were classified into one of seven groups based on their Frail-VIG score (0-0.15;
      0.16-0.25; 0.26-0.35; 0.36-0.45; 0.46-0.55; 0.56-0.65; and 0.66-1). Survival
      curves for these groups were compared using the log-rank test. ROC curves were
      used to assess the index's capacity to predict mortality at 24 months. RESULTS:
      Mean (standard deviation) patient age was 86.4 (5.6) years. The 24-month
      mortality rate was 57.3% for the whole sample. Significant between-group
      (deceased vs. living) differences (p < 0.05) were observed for most index
      variables. Survival curves for the seven Frail-VIG groups differed significantly
      (X2 = 433.4, p < 0.001), with an area under the ROC curve (confidence interval)
      of 0.90 (0.88-0.92) at 12 months and 0.85 (0.82-0.88) at 24 months.
      Administration time for the Frail-VIG index ranged from 5 to 10 min. CONCLUSIONS:
      The Frail-VIG index, which requires less time to administer than previously
      validated FIs, presents a good discriminative capacity for the degree of frailty
      and a high predictive capacity for mortality in the present cohort. Although more
      research is needed to confirm the validity of this instrument in other
      populations and settings, the Frail-VIG may provide clinicians with a RGA method
      and also a reliable tool to assess frailty in routine practice.

PMID- 29373969
TI  - miR-34a is involved in CSE-induced apoptosis of human pulmonary microvascular
      endothelial cells by targeting Notch-1 receptor protein.
AB  - BACKGROUND: Abnormal apoptosis of lung endothelial cells has been observed in
      emphysematous lung tissue and has been suggested to be an important upstream
      event in the pathogenesis of chronic obstructive pulmonary disease (COPD).
      Studies have shown that microRNAs (miRNAs) contribute to the pathogenesis of
      pulmonary diseases by regulating cell apoptosis. The present study was designed
      to investigate the expression of microRNA-34a (miR-34a) in human pulmonary
      microvascular endothelial cells (HPMECs) exposed to cigarette smoke extract
      (CSE), and the potential regulatory role of miR-34a in endothelial cell
      apoptosis. RESULTS: Our results showed that the expression of miR-34a was
      significantly increased in CSE-treated HPMECs, and inhibiting miR-34a attenuated
      CSE-induced HPMEC apoptosis. Furthermore, expression of Notch-1, a receptor
      protein in the Notch signalling pathway, was decreased and was inversely
      correlated with miR-34a expression in HPMECs treated with CSE. Computational
      miRNA target prediction confirmed that Notch-1 is a target of miR-34a. Luciferase
      reporter assay further confirmed the direct interaction between miR-34a and the
      3'-untranslated region (UTR) of Notch-1. Restoration of Notch-1 pathway was able
      to partially block the effect of miR-34a on HPMEC apoptosis. These results
      indicate that Notch-1 is a critical downstream target of miR-34a in regulating
      the CSE-induced HPMEC apoptosis. CONCLUSIONS: Our results suggest that miR-34a
      plays a key role in CSE-induced endothelial cell apoptosis by directly regulating
      its target gene Notch-1 in endothelial cells.

PMID- 29373970
TI  - Role of L-carnitine in female infertility.
AB  - BACKGROUND: L-carnitine (LC), and its acetylated form, acetyl L-carnitine (ALC),
      have immense functional capabilities to regulate the oxidative and metabolic
      status of the female reproductive system. The vulnerability of this system to
      free radicals demand for advanced strategies to combat them. For this purpose,
      the 'quasi vitamins' LC and ALC can be used either individually, or in
      combination with each other or with other antioxidants. MAIN BODY: This review
      (a) summarizes the effects of carnitines on female fertility along with the
      findings from various in vivo and in vitro studies involving human, animal and
      assisted reproductive technology, and (b) proposes their mechanism of actions in
      improving female fertility through their integrated actions on reducing cellular
      stress, maintaining hormonal balance and enhancing energy production. They
      reportedly aid beta-oxidation in oocytes, maintain its cell membrane stability by
      acetylation of phospholipids and amphiphilic actions, prevent free radical
      induced DNA damage and also stabilize acetyl Co-A/Co-A ratio for adequate acetyl
      storage as energy supply to maintain the robustness of reproductive cells.
      CONCLUSION: While both LC and ALC have their applications in improving female
      fertility, ALC is preferred for its better antioxidant properties and LC for
      amelioration of energy supply to the cells. These beneficial effects show great
      promise in its application as a treatment option for women facing infertility
      disorders.

PMID- 29373971
TI  - Development and application of an indirect enzyme-linked immunosorbent assay
      based on recombinant capsid protein for the detection of mink circovirus
      infection.
AB  - BACKGROUND: Mink circovirus (MiCV) is a newly discovered pathogen associated with
      mink diarrhea. The prevalence and economic importance of this virus remain poorly
      understood, and no specific serological assay has been developed for the
      diagnosis of MiCV infection. RESULTS: In this study, a recombinant capsid protein
      antigen expressed in Escherichia coli was utilized to establish an indirect
      enzyme-linked immunosorbent assay (iELISA). Results revealed that the assay had
      no cross-reactivity with other related pathogens, and the respective sensitivity
      and specificity of the proposed iELISA were 92.31% and 91.67% compared with those
      obtained of Western blot on 138 serum samples from minks. The correlation
      coefficient between iELISA and Western blot was 0.838 (p > 0.05). iELISA was
      applied to detect MiCV antibodies in 683 clinical serum samples from different
      farms from the major mink industry province in China, and 21 of 24 farms with 163
      of 683 (23.87%) individuals were tested positive for MiCV antibodies. The
      positive rates of each of the 21 flocks ranged from 2.33% to 73.68%. CONCLUSIONS:
      These results indicated that iELISA was a sensitive and specific method suitable
      for the large-scale detection of MiCV infections in mink. This study provided an
      effective method for the serological diagnosis and positive rate investigation of
      MiCV infection.

PMID- 29373973
TI  - Factors deterring dentistry, medical, pharmacy, and social science undergraduates
      from pursuing nursing as a healthcare career: a cross-sectional study in an Asian
      university.
AB  - BACKGROUND: Globally more registered nurses need to be recruited to meet the
      needs of aging populations and increased co-morbidity. Nursing recruitment
      remains challenging when compared to other healthcare programs. Despite
      healthcare students having similar motivation in joining the healthcare industry,
      many did not consider nursing as a career choice. This study aims to identify the
      deterrents to choosing nursing among healthcare undergraduates by examining the
      differences in the factors influencing healthcare career choices and nursing as a
      career choice. METHODS: A cross sectional study was conducted using a 35-parallel
      items instrument known as Healthcare Career Choice and Nursing Career Choice
      scale. Six hundred and four (n = 604) first year medical, pharmacy, dentistry and
      social science students from a university in Singapore completed the survey.
      RESULTS: Nursing as a career was perceived by healthcare students to be more
      likely influenced by prior healthcare exposure, the nature of the work, job
      prospects, and social influences. Lack of autonomous decision making, perceived
      lower ability to make diagnosis, having to attend to patients' hygiene needs,
      engendered stigma, and lack of parental support were identified as deterring
      factors to choosing nursing as a career. CONCLUSION: An understanding of the
      deterrents to choosing nursing as career allows policy makers and educational
      leaders to focus on recruitment strategies. These include providing more exposure
      to nurses' roles in early school years, helping young people to overcome the fear
      of providing personal hygiene care, promoting nurses' autonomous nursing
      practice, addressing gender stigma, and overcoming parental objection.

PMID- 29373972
TI  - Differential gene expression in the evolution of sex pheromone communication in
      New Zealand's endemic leafroller moths of the genera Ctenopseustis and
      Planotortrix.
AB  - BACKGROUND: Sex pheromone communication in moths has attracted the attention of
      evolutionary biologists due to the vast array of pheromone compounds used,
      addressing questions of how this diversity arose and how male reception has
      evolved in step with the female signal. Here we examine the role of changing gene
      expression in the evolution of mate recognition systems in leafroller moths,
      particularly focusing on genes involved in the biosynthetic pathways of sex
      pheromones in female pheromone glands and the peripheral reception repertoire in
      the antennae of males. From tissue-specific transcriptomes we mined and compared
      a database of genes expressed in the pheromone glands and antennae of males and
      females of four closely related species of leafroller moths endemic to New
      Zealand, Ctenopseutis herana and C. obliquana, and Planotortrix excessana and P.
      octo. The peculiarity of this group, compared to other Lepidoptera, is the use of
      (Z)-5-tetradecenyl acetate, (Z)-7-tetradecenyl acetate, and (Z)-8-tetradecenyl
      acetate as sex pheromone components. RESULTS: We identify orthologues of
      candidate genes from the pheromone biosynthesis pathway, degradation and
      transport, as well as genes of the periphery olfactory repertoire, including
      large families of binding proteins, receptors and odorant degrading enzymes. The
      production of distinct pheromone blends in the sibling species is associated with
      the differential expression of two desaturase genes, deast5 and desat7, in the
      pheromone glands. In male antennae, three odorant receptors, OR74, OR76a and OR30
      are over-expressed, but their expression could not be clearly associated with the
      detection of species-specific pheromones components. In addition these species
      contain duplications of all three pheromone binding proteins (PBPs) that are also
      differentially expressed among species. CONCLUSIONS: While in females differences
      in the expression of desaturases may be sufficient to explain pheromone blend
      differences among these New Zealand leafroller species, in males differential
      expression of several genes, including pheromone binding proteins, may underpin
      differences in the response by males to changing pheromone components among the
      species.

PMID- 29373974
TI  - Degree of mosaicism in trophectoderm does not predict pregnancy potential: a
      corrected analysis of pregnancy outcomes following transfer of mosaic embryos.
AB  - BACKGROUND: Preimplantation genetic screening (PGS) is increasingly utilized as
      an adjunct procedure to IVF. Recently healthy euploid live birth were reported
      following transfer of mosaic embryos. Several recent publications have surmised
      that the degree of trophectoderm (TE) mosaicism in transferred embryos is
      predictive of ongoing pregnancy and miscarriage rates. METHODS: This is a
      corrected analysis of previously published retrospective data on vitro
      fertilization (IVF) cycle outcomes involving replacement of 143 mosaic and 1045
      euploid embryos tested by PGS, utilizing high-resolution next-generation
      sequencing (NGS) of TE and determination of percentages of mosaicism. Receiver
      operating curves (ROCs) and measurement of area under the curve (AUC) were used
      to evaluated the accuracy of the predictor variable, proportion of aneuploid
      cells in a TE biopsy specimen, with IVF outcomes, ongoing pregnancy and
      miscarriage rates. RESULTS: Confirming findings of the previously published
      report we also found higher ongoing pregnancy rates (63.3% vs. 39.2%) and lower
      miscarriage rates (10.2% vs. 24.3%) with euploid embryo transfers than with
      mosaic embryo transfer. There, however, were no significant differences in
      ongoing pregnancy or miscarriage rates among mosaic embryo transfers at any
      threshold of aneuploidy. Based on AUC, TE biopsies predicted ongoing pregnancy
      for euploid, as well as mosaic embryos, in a range of 0.50 to 0.59 and
      miscarriage in a range from 0.50 to 0.66 CONCLUSIONS: Degree of TE mosaicism was
      a poor predictor of ongoing pregnancy and miscarriage.

PMID- 29373975
TI  - Evaluation of a community-based, family focused healthy weights initiative using
      the RE-AIM framework.
AB  - BACKGROUND: Childhood overweight and obesity is a major public health concern.
      Community-based interventions have the potential to reach caregivers and
      children. However, the overall health impact of these programs is rarely
      comprehensively assessed. This study evaluated a physical activity and healthy
      eating family program (Healthy Together; HT) using the RE-AIM framework. METHODS:
      Ten sites implemented the 5-week program. Thirty-nine staff members and 277
      program participants (126 caregivers [M age  = 35.6] and 151 children [M age  =
      13]) participated in the evaluation. Each RE-AIM dimension was assessed
      independently using a mixed-methods approach. Sources of data included archival
      records, interviews and surveys. Effectiveness outcome variables were assessed at
      pre- and post-intervention and 6-month follow-up. RESULTS: Reach: HT participants
      were almost entirely recruited from existing programs within sites.
      Effectiveness: Caregivers' nutrition related efficacy beliefs increased following
      HT (ps < .03). Participation in HT was not associated with significant changes in
      physical activity or nutrition behaviour or perceived social support (ps > .05).
      Knowledge surrounding healthy diets and physical activity increased in children
      and caregivers (ps < .05). Adoption: Thirty-five percent of sites approached to
      implement HT expressed interest. The 10 sites selected recruited existing staff
      members to implement HT. IMPLEMENTATION: Program objectives were met 72.8% of the
      time and 71 adaptations were made. HT was finance- and time-dependent.
      Maintenance: Two sites fully implemented HT in the follow-up year and 5 sites
      incorporated aspects of HT into other programs. CONCLUSIONS: Working alongside
      organizations that develop community programs to conduct comprehensive, arms
      length evaluations can systematically highlight areas of success and challenges.
      Overall HT represents a feasible community-based intervention; however further
      support is required in order to ensure the program is effective at positively
      targeting the desired outcomes. As a result of this evaluation, modifications are
      currently being implemented to HT.

PMID- 29373976
TI  - Calculating census tract-based life expectancy in New York state: a generalizable
      approach.
AB  - BACKGROUND: Life expectancy at birth (LE) has been calculated for states and
      counties. LE estimates at these levels mask health disparities in local
      communities. There are no nationwide estimates at the sub-county level. We
      present a stepwise approach for calculating LE using census tracts in New York
      state to identify health disparities. METHODS: Our study included 2751 census
      tracts in New York state, but excluded New York City. We used population data
      from the 2010 United States Census and 2008-2010 mortality data from the state
      health department. Tracts were assigned to 99.97% of the deaths. We removed
      tracts which had a majority of people living in group quarters. Deaths in these
      tracts are often recorded elsewhere. Of the remaining 2679 tracts, 6.6% of the
      tracts had standard errors >= 2 years. A geographic aggregation tool was used to
      aggregate tracts with fewer than 60 deaths, and then aggregate areas that had
      standard errors of >= 2 years. RESULTS: Aggregation resulted in a 9.9% reduction
      in the number of areas. Tracts with < 2% of population living below the poverty
      level had a LE of 82.8 years, while tracts with a poverty level >= 25% had a LE
      of 75.5. We observed differences in LE in border areas, of up to 10.4 years, when
      excluding or including deaths of study area residents that occurred outside the
      study area. The range and standard deviation at the county level (77.5-82.8, SD =
      1.2 years) were smaller than our final sub-county areas (64.7-92.0, SD = 3.3
      years). The correlation between LE and poverty were similar and statistically
      significant (p < 0.0001) at the county (r = - 0.58) and sub-county level (r = -
      0.58). The correlations between LE and percent African-American at the county
      level were (r = 0.11, p = 0.43) and at the sub-county level (r = - 0.25, p <
      0.0001). CONCLUSION: The proposed approach for geocoding and aggregation of
      mortality and population data provides a solution for health departments to
      produce stable empirically-derived LE estimates using data coded to the tract.
      Reliable estimates within sub-county areas are needed to aid public health
      officials in focusing preventive health programs in areas where health
      disparities would be masked by county level estimates.

PMID- 29373978
TI  - Is ERAS effective and safe in laparoscopic gastrectomy for gastric carcinoma? A
      meta-analysis.
AB  - BACKGROUND: It is still unclear whether enhanced recovery after surgery is
      effective and safe in laparoscopic gastrectomy for gastric carcinoma. METHODS:
      Cochrane library databases, Medline, Embase, and Pubmed were searched from
      January 1, 1986, to December 31, 2016. Randomized controlled trials (RCTs)
      comparing fast-track recovery with conventional recovery strategies in
      laparoscopic radical gastrectomy for gastric carcinoma were included. The main
      outcomes measured were postoperative hospital stay, time to first flatus,
      hospital charge, and overall complication rate. RESULTS: Six RCTs with 400
      patients were included in this study. Fast-track surgery has shorter
      postoperative hospital stays (weighted mean difference (WMD) - 2.65; 95% CI, -
      4.01 to - 1.29, z = 3.82, P < 0.01) and less hospitalization expenditure (WMD -
      523.43; 95% CI, - 799.79 to - 247.06, z = 3.71, P < 0.01) than conventional
      recovery strategies. There was no significant difference with respect to duration
      to first flatus (WMD - 17.72; 95% CI, - 39.46-4.02, z = 1.60, P = 0.11) and
      complication rate (OR 1.57; 95% CI, 0.82-2.98, z = 1.37, P = 0.17). CONCLUSIONS:
      Enhanced recovery after surgery is effective and safe and is thus recommended in
      laparoscopic radical gastrectomy for gastric carcinoma.

PMID- 29373977
TI  - Association of thrombocytosis with COPD morbidity: the SPIROMICS and COPDGene
      cohorts.
AB  - BACKGROUND: Thrombocytosis has been associated with COPD prevalence and increased
      all-cause mortality in patients with acute exacerbation of COPD (AECOPD); but
      whether it is associated with morbidity in stable COPD is unknown. This study
      aims to determine the association of thrombocytosis with COPD morbidity including
      reported AECOPD, respiratory symptoms and exercise capacity. METHODS:
      Participants with COPD were included from two multi-center observational studies
      (SPIROMICS and COPDGene). Cross-sectional associations of thrombocytosis
      (platelet count >=350 * 109/L) with AECOPD during prior year (none vs. any),
      exertional dyspnea (modified Medical Research Council (mMRC) score >= 2), COPD
      Assessment Test (CAT) score >= 10, six-minute-walk distance (6MWD), and St.
      George Respiratory questionnaire (SGRQ) were modeled using multivariable logistic
      or linear regression. A pooled effect estimate for thrombocytosis was produced
      using meta-analysis of data from both studies. RESULTS: Thrombocytosis was
      present in 124/1820 (6.8%) SPIROMICS participants and 111/2185 (5.1%) COPDGene
      participants. In meta-analysis thrombocytosis was associated with any AECOPD
      (adjusted odds ratio [aOR] 1.5; 95% confidence interval [95% CI]: 1.1-2.0),
      severe AECOPD (aOR 1.5; 95% CI: 1.1-2.2), dyspnea (mMRC >= 2 aOR 1.4; 95% CI: 1.0
      1.9), respiratory symptoms (CAT >= 10 aOR 1.6; 95% CI: 1.1-2.4), and higher SGRQ
      score (beta 2.7; 95% CI: 0.5, 5). Thrombocytosis was also associated with
      classification into Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      group D (aOR 1.7 95% CI: 1.2-2.4). CONCLUSIONS: Thrombocytosis was associated
      with higher likelihood of prior exacerbation and worse symptoms. Platelet count,
      a commonly measured clinical assay, may be a biomarker for moderate-severe COPD
      symptoms, guide disease classification and intensity of treatment. Future
      longitudinal studies investigating the role of platelets in COPD progression may
      be warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01969344 (SPIROMICS) and
      NCT00608764 (COPDGene).

PMID- 29373979
TI  - Identification and genome analysis of tomato chlorotic spot virus and dsRNA
      viruses from coinfected vegetables in the Dominican Republic by high-throughput
      sequencing.
AB  - The Tomato chlorotic spot virus (TCSV) was first reported in the 1980s, having
      its occurrence limited to Brazil and Argentina. Due to an apparent mild severity
      in the past, molecular studies concerning TCSV were neglected. However, TCSV has
      disseminated over the USA and Caribbean countries. In Dominican Republic TCSV has
      been recently reported on important cultivated crops such as pepper and beans. In
      this work, we provide the first complete genome of a TCSV isolate from
      symptomatic plants in Dominican Republic, which was obtained by high-throughput
      sequencing. In addition, three dsRNA viruses from different virus families were
      identified coinfecting these plants Bell pepper endornavirus (BPEV), Southern
      tomato virus (STV) and Pepper cryptic virus 2 (PCV-2). Phylogenetic analysis
      showed that the Dominican Republic TCSV isolate has a close relationship with
      other TCSV isolates and a reassortant isolate between TCSV and Groundnut ringspot
      virus (GRSV), all found in USA. BPEV, STV and PCV-2 isolates from Dominican
      Republic were close related to corresponding American isolates. The possible
      biological implications of these virus-mixed infections are discussed.

PMID- 29373980
TI  - Do we need new trials of procalcitonin-guided antibiotic therapy?
AB  - Using biomarkers as a guide to tailor the duration of antibiotic treatment in
      respiratory infections is an attractive hypothesis assessed in several studies.
      Recent work aiming to summarize the evidence assessed the effect of a
      procalcitonin (PCT)-guided antibiotic treatment on outcomes in acute lower
      respiratory tract infections (LRTI), suggesting that significant reductions in
      antibiotic duration occur when using a PCT-guided algorithm. However,
      controversial evidence also suggested PCT-guided algorithms were associated with
      increased antibiotic duration and increased incidence of Clostridium difficile,
      without any impact on mortality, in real-world settings. So, although using PCT
      guided antibiotic stewardship is promising, after more than a decade of
      randomized controlled trials on this topic the evidence in its favor is still
      less than compelling due to limitations in trial design, not taking into
      consideration fundamental aspects of PCT biology, and the absence of evidence
      based antimicrobial duration in intervention and control groups. In this
      commentary we highlight some questions and limitations of primary PCT study data
      that might impact interpretation and clinical use of PCT at the bedside.

PMID- 29373981
TI  - Assessment of anxiety-depression levels and perceptions of quality of life in
      adolescents with dysmenorrhea.
AB  - BACKGROUND: This study aimed to assess the anxiety-depression levels and the
      perceptions of quality of life, as well as the factors affecting these variables,
      in adolescents with dysmenorrhea. METHODS: The participants included 60
      adolescents with dysmenorrhea and 41 healthy adolescents between the ages of 12
      and 18. This study used the Pediatric Quality of Life Inventory (PedsQL) for
      assessing the perceptions of quality of life, the State-Trait Anxiety Inventory
      (STAI) for measuring anxiety levels, and the Children's Depression Inventory
      (CDI) for measuring depression levels. RESULTS: It was determined that compared
      to healthy controls, the depression and anxiety scores were higher and the
      quality of life was impaired in adolescents with dysmenorrhea. In addition, it
      was shown that the depression and anxiety levels increased and the psychosocial
      health subscale scores of quality of life decreased with increasing dysmenorrhea
      severity. However, the likelihood of dysmenorrhea was found to be higher with
      increasing depression scores, while the anxiety levels had no effect on
      dysmenorrhea. CONCLUSION: In dysmenorrhea management, it is important to enhance
      awareness among pediatric clinicians and gynecologists regarding the associations
      between dysmenorrhea and mental problems.

PMID- 29373982
TI  - Secoisolariciresinol diglucoside is a blood-brain barrier protective and anti
      inflammatory agent: implications for neuroinflammation.
AB  - BACKGROUND: Secoisolariciresinol diglucoside (SDG), the main lignan in flaxseed,
      is known for its beneficial effects in inflammation, oxidative stress, heart
      disease, tumor progression, atherosclerosis, and diabetes. SDG might be an
      attractive natural compound that protects against neuroinflammation. Yet, there
      are no comprehensive studies to date investigating the effects of SDG on brain
      endothelium using relevant in vivo and in vitro models. METHODS: We evaluated the
      effects of orally administered SDG on neuroinflammatory responses using in vivo
      imaging of the brain microvasculature during systemic inflammation and aseptic
      encephalitis. In parallel, the anti-inflammatory actions of SDG on brain
      endothelium and monocytes were evaluated in vitro blood-brain barrier (BBB)
      model. Multiple group comparisons were performed by one-way analysis of variance
      with Dunnet's post hoc tests. RESULTS: We found that SDG diminished leukocyte
      adhesion to and migration across the BBB in vivo in the setting of aseptic
      encephalitis (intracerebral TNFalpha injection) and prevented enhanced BBB
      permeability during systemic inflammatory response (LPS injection). In vitro SDG
      pretreatment of primary human brain microvascular endothelial cells (BMVEC) or
      human monocytes diminished adhesion and migration of monocytes across brain
      endothelial monolayers in conditions mimicking CNS inflammatory responses.
      Consistent with our in vivo observations, SDG decreased expression of the
      adhesion molecule, VCAM1, induced by TNFalpha, or IL-1beta in BMVEC. SDG
      diminished expression of the active form of VLA-4 integrin (promoting leukocyte
      adhesion and migration) and prevented the cytoskeleton changes in primary human
      monocytes activated by relevant inflammatory stimuli. CONCLUSION: This study
      indicates that SDG directly inhibits BBB interactions with inflammatory cells and
      reduces the inflammatory state of leukocytes. Though more work is needed to
      determine the mechanism by which SDG mediates these effects, the ability of SDG
      to exert a multi-functional response reducing oxidative stress, inflammation, and
      BBB permeability makes it an exciting potential therapeutic for neuroinflammatory
      diseases. SDG can serve as an anti-inflammatory and barrier-protective agent in
      neuroinflammation.

PMID- 29373983
TI  - Safety and efficacy of hematopoietic and mesanchymal stem cell therapy for
      treatment of T1DM: a systematic review and meta-analysis protocol.
AB  - INTRODUCTION: Insulin standard treatment of T1DM cannot cure the patients as
      different chronic complications occurred subsequently. Investigations on a
      curative treatment in T1DM propose cell replacement or maintenance instead of
      exogenous insulin therapy, but different dimensions of this novel treatment are
      not clarified. METHODS AND ANALYSIS: We will include all clinical trials which
      have evaluated the efficacy MSC or HSC transplantation in T1DM treatment;
      electronically search bibliographic databases, country registration data banks,
      and gray literatures; and hand-search two key journals, two experts' article, and
      references of the included articles with no language restriction. Primary outcome
      is the extent of reduction in insulin requirement and secondary outcomes are
      safety of MSC and HSC therapy, effect of this therapy on diabetic parameters,
      effect of the rout of transplantation and origin of the MSC or HSC on efficacy of
      treatment, studies heterogeneity and potential reasons of it. Heterogeneity and
      its severity will be calculated with Q Cochrane test, P value, and I2 index.
      STATA software version 12 will be used for meta-analysis. PROSPERO Registration
      number: CRD42016047176. ETHICS AND DISSEMINATION: We will publish the systematic
      review in a peer review journal; as it presents an analysis of published
      literature, the study does not require ethical approval. STRENGTHS AND
      LIMITATIONS OF THIS STUDY: This systematic review and meta-analysis will
      investigate the efficacy of MSC and HSC transplantation in T1DM treatment with no
      language restriction. Also we will evaluate gray literatures after hand
      searching. This protocol is prepared according to Preferred Reporting Items for
      Systematic Review and Meta-Analysis Protocols (PRISMA-P). Two reviewers will
      evaluate screened full texts, extract data, and asses risk of bias of eligible
      primary studies independently. As there is the possibility that we miss some
      unpublished primary studies due to negative results, we will use funnel plot to
      detect this and correct it with fill and trim method.

PMID- 29373984
TI  - The effect of targeted exercise on knee-muscle function in patients with
      persistent hamstring deficiency following ACL reconstruction - study protocol for
      a randomized controlled trial.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) reconstruction, using hamstring auto
      graft is a common surgical procedure, which often leads to persistent hamstring
      muscle-strength deficiency and reduced function. The purpose of this randomized
      controlled trial (RCT) is to investigate the effect of a combined, progressive,
      strength and neuromuscular exercise intervention on knee muscle strength,
      functional capacity and hamstring muscle-tendon morphology in ACL-reconstructed
      patients with persistent hamstring muscle-strength deficiency compared with
      controls. METHODS/DESIGN: The study is designed as a multicenter, parallel-group
      RCT with balanced randomization (1:1) and blinded outcome assessments (level of
      evidence: II) and will be reported in accordance with the CONSORT Statement.
      Fifty ACL-reconstructed patients (hamstring auto-graft) with persistent limb-to
      limb knee-flexor muscle-strength asymmetry at 12-24 months' post surgery, will be
      recruited through outpatient clinics and advertisements. Patients will be
      randomized to a 12-week progressive, strength and neuromuscular exercise group
      (SNG) with supervised training twice weekly or a control intervention (CON)
      consisting of a home-based, low-intensity exercise program. Outcome measures
      include between-group change in maximal isometric knee-flexor strength (primary
      outcome) and knee-extensor muscle strength, hamstring-to-quadriceps strength
      ratios of the leg that has been operated on and Knee injury and Osteoarthritis
      Outcome Score (KOOS) (secondary outcomes). In addition, several explorative
      outcomes will be investigated: The International Knee Documentation Committee
      Subjective Knee Form (IKDC), the Tegner Activity Score, rate of force development
      (RFD) for the knee flexors and extensors, tendon regeneration and potential
      muscle hypertrophy at graft harvest site evaluated by magnetic resonance imaging
      (MRI), postural control, kinetic/kinematic gait characteristics and knee-related
      functional capacity. DISCUSSION: This RCT is designed to investigate the effect
      of combined, progressive-resistance and neuromuscular exercises on knee
      flexor/extensor strength, in the late rehabilitation phase following ACL
      reconstruction. Reduced hamstring strength represents a potential risk factor for
      secondary ACL rupture and accelerated progression of osteoarthritis. If deemed
      effective, the intervention paradigm introduced in this study may help to improve
      current treatment strategies in ACL-reconstructed patients. TRIAL REGISTRATION:
      ClinicalTrials.gov, ID: NCT02939677 (recruiting). Registered on 20 October 2016.

PMID- 29373985
TI  - Reversal of end-stage heart failure in juvenile hemochromatosis with iron
      chelation therapy: a case report.
AB  - BACKGROUND: Juvenile hemochromatosis is the most severe form of iron overloading
      phenotype. Although rare, it should be suspected in patients who present with
      hypogonadotropic hypogonadism, diabetes mellitus, or cardiomyopathy without a
      clear cause. CASE PRESENTATION: A young Serbian male presenting with end-stage
      heart failure was referred for extracorporeal membrane oxygenation. An
      endomyocardial biopsy revealed cytoplasmic iron deposits in myocytes. His
      condition was stabilized with biventricular assist devices and he was listed for
      heart transplantation. Iron chelation therapy was commenced and resulted in rapid
      removal of iron burden. Serial outpatient echocardiograms demonstrated myocardial
      recovery such that a successful biventricular assist device explant occurred 131
      days after initial implant. Targeted gene sequencing revealed a loss-of-function
      mutation within the HJV gene, which is consistent with juvenile hemochromatosis.
      CONCLUSIONS: This rare case of a patient with juvenile hemochromatosis associated
      with a HJV mutation provides histologic evidence documenting the reversal of
      associated end-stage heart failure, requiring emergent mechanical circulatory
      support, with iron chelation therapy.

PMID- 29373986
TI  - Etiological heterogeneity and clinical variability in newborns with esophageal
      atresia.
AB  - BACKGROUND: The aim of this study was to define different characteristics of
      infants with esophageal atresia and correlations with neonatal level of care,
      morbidity and mortality occurring during hospital stay. METHODS: Charts of all
      newborns with esophageal atresia (EA) admitted to our University NICU between
      January 2003 and November 2016 were reviewed and subdivided in four groups
      related to different clinical presentations; EA as an isolated form (A), with a
      concomitant single malformation (B), as VACTERL association (C), and in the
      context of a syndrome or an entity of multiple congenital anomalies (D). RESULTS:
      We recruited 67 infants with EA (with or without tracheoesophageal fistula),
      distributed in groups as follows: A 31.3%, B 16.4%, C 26.8% and D 25.3%. Type of
      atresia was not statistically different among different groups. Mortality was
      higher in groups C and D, especially if associated with congenital heart defects.
      In survivors, we found different auxological evolution and prognostic profiles
      considering duration in days of invasive mechanical ventilation and total
      parenteral nutrition, as well as length of stay and corrected gestational age at
      discharge. CONCLUSIONS: In the context of genetic and syndromic entities,
      subjects with VACTERL association showed a lower mortality rate although a higher
      and more complex level of intensive care was noted in comparison to infants
      without VACTERL genetic and syndromic entities.

PMID- 29373987
TI  - Hospital recruitment for a pragmatic cluster-randomized clinical trial: Lessons
      learned from the COMPASS study.
AB  - BACKGROUND: Pragmatic randomized clinical trials are essential to determine the
      effectiveness of interventions in "real-world" clinical practice. These trials
      frequently use a cluster-randomized methodology, with randomization at the site
      level. Despite policymakers' increased interest in supporting pragmatic
      randomized clinical trials, no studies to date have reported on the unique
      recruitment challenges faced by cluster-randomized pragmatic trials. We
      investigated key challenges and successful strategies for hospital recruitment in
      the Comprehensive Post-Acute Stroke Services (COMPASS) study. METHODS: The
      COMPASS study is designed to compare the effectiveness of the COMPASS model
      versus usual care in improving functional outcomes, reducing the numbers of
      hospital readmissions, and reducing caregiver strain for patients discharged home
      after stroke or transient ischemic attack. This model integrates early supported
      discharge planning with transitional care management, including nurse-led follow
      up phone calls after 2, 30, and 60 days and an in-person clinic visit at 7-14
      days involving a functional assessment and neurological examination. We present
      descriptive statistics of the characteristics of successfully recruited hospitals
      compared with all eligible hospitals, reasons for non-participation, and
      effective recruitment strategies. RESULTS: We successfully recruited 41 (43%) of
      95 eligible North Carolina hospitals. Leading, non-exclusive reasons for non
      participation included: insufficient staff or financial resources (n = 33, 61%),
      lack of health system support (n = 16, 30%), and lack of support of individual
      decision-makers (n = 11, 20%). Successful recruitment strategies included:
      building and nurturing relationships, engaging team members and community
      partners with a diverse skill mix, identifying gatekeepers, finding mutually
      beneficial solutions, having a central institutional review board, sharing
      published pilot data, and integrating contracts and review board administrators.
      CONCLUSIONS: Although we incorporated strategies based on the best available
      evidence at the outset of the study, hospital recruitment required three times as
      much time and considerably more staff than anticipated. To reach our goal, we
      tailored strategies to individuals, hospitals, and health systems. Successful
      recruitment of a sufficient number and representative mix of hospitals requires
      considerable preparation, planning, and flexibility. Strategies presented here
      may assist future trial organizers in implementing cluster-randomized pragmatic
      trials. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02588664 . Registered on 23
      October 2015.

PMID- 29373988
TI  - Who should conduct ethnobotanical studies? Effects of different interviewers in
      the case of the Chacobo Ethnobotany project, Beni, Bolivia.
AB  - BACKGROUND: That the answers elicited through interviews may be influenced by the
      knowledge of the interviewer is accepted across disciplines. However, in
      ethnobotany, there is little evidence to quantitatively assess what impact this
      effect may have. We use the results of a large study of traditional ecological
      knowledge (TEK) of plant use of the Chacobo and Pacahuara of Beni, Bolivia, to
      explore the effects of interviewer identity and knowledge upon the elicited plant
      species and uses. METHODS: The Chacobo are a Panoan speaking tribe of about 1000
      members (300+ adults) in Beni, Bolivia. Researchers have collected
      anthropological and ethnobotanical data from the Chacobo for more than a century.
      Here, we present a complete ethnobotanical inventory of the entire adult Chacobo
      population, with interviews and plant collection conducted directly by Chacobo
      counterparts, with a focus on the effects caused by external interviewers.
      RESULTS: Within this large study, with a unified training for interviewers, we
      did find that different interviewers did elicit different knowledge sets, that
      some interviewers were more likely to elicit knowledge similar to their own, and
      that participants interviewed multiple times often gave information as different
      as that from two randomly chosen participants. CONCLUSIONS: Despite this, we did
      not find this effect to be overwhelming-the amount of knowledge an interviewer
      reported on the research subject had comparatively little effect on the amount of
      knowledge that interviewer recorded from others, and even those interviewers who
      tended to elicit similar answers from participants also elicited a large
      percentage of novel information.

PMID- 29373989
TI  - Effectiveness and safety of bifidobacteria and berberine in people with
      hyperglycemia: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Berberine is one of the most important examples of a Chinese
      traditional medicine that has hypoglycemic effects but there have been no
      randomized controlled trials of the drug in a larger sample. In addition, the use
      of probiotic biotherapy to maintain an appropriate intestinal flora may represent
      an effective early intervention for hyperglycemia. Unfortunately, there has been
      a shortage of relevant research on this possibility at the population level. This
      study was designed to determine the hypoglycemic effect and safety of both
      bifidobacteria and berberine administration to newly diagnosed patients with pre
      diabetes or diabetes mellitus. METHODS/DESIGN: This is a multicenter, double
      blind, randomized, and parallel-controlled study that includes a run-in period of
      2 weeks and a treatment period of 16 weeks, which will be conducted between June
      2015 and October 2018. The 300 randomized patients will be assigned to the
      following four groups for 16 weeks' treatment: Bifidobacterium, berberine,
      Bifidobacterium combined berberine, and placebo control groups. The primary
      outcome is the absolute value of fasting plasma glucose compared with baseline
      after 16 weeks of treatment. DISCUSSION: This is the first randomized controlled
      trial to determine the hypoglycemic effect and safety of both bifidobacteria and
      berberine administration to newly diagnosed patients with pre-diabetes or
      diabetes mellitus. It may provide support for the use of berberine and
      bifidobacteria in the treatment of diabetes. TRIAL REGISTRATION:
      ClinicalTrials.gov, ID: NCT03330184 . Retrospectively registered on 18 October
      2017.

PMID- 29373990
TI  - Targeted next-generation sequencing analysis in couples at increased risk for
      autosomal recessive disorders.
AB  - BACKGROUND: Many of the genetic childhood disorders leading to death in the pre-
      or neonatal period or during early childhood follow autosomal recessive modes of
      inheritance and bear specific challenges for genetic counseling and prenatal
      diagnostics. Parents are carriers but clinically unaffected, and diseases are
      rare but have recurrence risks of 25% in the same family. Often, affected
      children (or fetuses) die before a genetic diagnosis can be established, post
      mortem analysis and phenotypic descriptions are insufficient and DNA from
      affected fetuses or children is not available for later analysis. A genetic
      diagnosis showing biallelic causative mutations is, however, the requirement for
      targeted carrier testing in parents and prenatal and preimplantation genetic
      diagnosis in further pregnancies. METHODS: We undertook targeted next-generation
      sequencing (NGS) for carrier screening of autosomal recessive lethal disorders in
      8 consanguineous and 5 non-consanguineous couples with one or more affected
      children. We searched for heterozygous variants (non-synonymous coding or splice
      variants) in parents' DNA, using a set of 430 genes known to be causative for
      rare autosomal recessive diseases with poor prognosis, and then filtering for
      variants present in genes overlapping in both partners. Putative pathogenic
      variants were tested for cosegregation in affected fetuses or children where
      material was available. RESULTS: The diagnosis for the premature death in
      children was established in 5 of the 13 couples. Out of the 8 couples in which no
      causative diagnosis could be established 4 consented to undergo further analysis,
      in two of those a potentially causative variant in a novel candidate gene was
      identified. CONCLUSIONS: For the families in whom causative variants could be
      identified, these may now be used for prenatal and preimplantation genetic
      diagnostics. Our data show that NGS based gene panel sequencing of selected genes
      involved in lethal autosomal recessive disorders is an effective tool for carrier
      screening in parents and for the identification of recessive gene defects and
      offers the possibility of prenatal and preimplantation genetic diagnosis in
      further pregnancies in families that have experienced deaths in early childhood
      and /or multiple abortions.

PMID- 29373991
TI  - Ethnomycological knowledge in three communities in Amealco, Queretaro, Mexico.
AB  - BACKGROUND: Fungi have multiple uses in temperate areas of Mexico, but an
      important decrease in the traditional knowledge of uses and customs of mushrooms
      becomes a fundamental issue for fungi conservation. However, only few studies
      quantify the traditional ethnomycological knowledge in Mexico, and this study is
      the first quantitative report for Queretaro, a central state with both Otomi and
      Mestizo communities and a high fungi diversity. METHODS: The present study was
      conducted registering traditional knowledge on the use and consumption of
      mushrooms in three Hnahnu (Otomi) communities (Tesquedo, Xajay, and Tenasda) in
      Amealco de Bonfil, Queretaro, Mexico, between August 2013 and November 2014. We
      conducted a stratified sampling, where uses common Hnahnu and Spanish names, and
      eight quantitative variables that conform the "Edible Mushrooms Cultural
      Significant Index" (EMCI) were recorded from 100 informants. For the
      classification and ordination analysis of species and uses, we used multivariate
      techniques such as cluster, multidimensional scaling, and principal components
      (PC). RESULTS: Thirty-three mushrooms species were registered, most of them used
      for consumption by households, few aimed for commercial purposes, one species is
      medicinal, another has veterinary, and other ludic uses (as a toy). The three
      species with the highest EMCSI were Amanita basii, Fistulinella wolfeana, and
      Lactarius indigo. Edibility was the main use detected in the survey, and people
      harvested mushrooms provided by the forest mainly during the rainy season. We
      observed that mushroom searching and collection are activities that strengthen
      the family ties and are crucial for the transfer of this knowledge through
      generations. Cluster analysis separates groups according to different values in
      EMCSI variables, and principal components ordinate the species by frequencies
      (PC1) and traditions (PC2). CONCLUSIONS: The current state of knowledge in the
      studied communities is strong, especially among women, but with a tendency to
      disappear due to migration and lack of interest among new generations. Future
      quantitative studies are important to analyze tendencies of the traditional
      ethnomycological knowledge transferred to new generations.

PMID- 29373993
TI  - A hybrid type I trial to increase Veterans' access to insomnia care: study
      protocol for a randomized controlled trial.
AB  - BACKGROUND: Chronic insomnia is among the most reported complaints of Veterans
      and military personnel referred for mental health services. It is highly comorbid
      with medical and psychiatric disorders, and is associated with significantly
      increased healthcare utilization and costs. Evidence-based psychotherapy, namely
      Cognitive Behavioral Therapy for Insomnia (CBTI), is an effective treatment and
      recommended over prescription sleep medications. While CBTI is part of a
      nationwide rollout in the Veterans Health Administration to train hundreds of
      providers, access to treatment is still limited for many Veterans due to limited
      treatment availability, low patient and provider knowledge about treatment
      options, and Veteran barriers such as distance and travel, work schedules, and
      childcare. Uptake of a briefer, more primary-care-friendly treatment into routine
      clinical care in Veterans Affairs (VA) primary care settings, where insomnia is
      typically first recognized and diagnosed, may effectively and efficiently
      increase access to effective insomnia interventions and help decrease the risks
      and burdens related to chronic insomnia. METHODS: This hybrid type I trial is
      composed of two aims. The first preliminarily tests the clinical non-inferiority
      of Brief Behavioral Treatment for Insomnia (BBTI) versus the current "gold
      standard" treatment, CBTI. The second is a qualitative needs assessment, guided
      by the Consolidated Framework for Implementation Research (CFIR), to identify
      potential factors that may affect successful implementation and integration of
      behavioral treatments for insomnia in the primary care setting. To identify
      potential implementation factors, individual interviews are conducted with the
      Veterans who participate in the clinical trial, as well as VA primary care
      providers and nursing staff. DISCUSSION: It is increasingly important to better
      understand barriers to, and facilitators of, implementing insomnia interventions
      in order to ensure that Veterans have the best access to care. Furthermore, it is
      important to evaluate the potential for new avenues of treatment delivery, like
      BBTI in the primary care setting, which can benefit Veterans who may not have
      adequate access to specialty mental health providers trained in CBTI. TRIAL
      REGISTRATION: ClinicalTrials.gov, ID: NCT02724800 . Registered on 31 March 2016.

PMID- 29373994
TI  - Combined miglustat and enzyme replacement therapy in two patients with type 1
      Gaucher disease: two case reports.
AB  - BACKGROUND: Intravenous enzyme replacement therapy is a first-line therapy for
      Gaucher disease type 1, and substrate reduction therapy represents an oral
      treatment alternative. Both enzyme replacement therapy and substrate reduction
      therapy are generally used as monotherapies in Gaucher disease. However, one
      randomized study and several case reports have described combination therapy over
      short time periods. CASE PRESENTATION: We report two female Gaucher disease type
      1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement
      therapy and miglustat substrate reduction therapy were administered to overcome
      refractory clinical symptoms. The first patient was diagnosed at age 17 and
      developed Gaucher disease-related bone manifestations that worsened despite
      starting imiglucerase enzyme replacement therapy. After switching to miglustat
      substrate reduction therapy, her bone symptoms improved, but she developed
      tremors and eventually switched back to enzyme replacement therapy. Miglustat was
      later recommenced in combination with ongoing enzyme replacement therapy due to
      continued bone pain, and her bone symptoms improved along with maintained
      visceral manifestations. Enzyme replacement therapy was subsequently tapered off
      and the patient has since been successfully maintained on miglustat. The second
      patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement
      therapy aged 15. After 9 years on enzyme replacement therapy she switched to
      miglustat substrate reduction therapy and her core symptoms were
      maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later
      added as a boost to therapy and her symptoms were subsequently maintained over a
      2.3-year period. However, miglustat was discontinued due to her relocation,
      necessitating an increase in enzyme replacement therapy dose. Overall, both
      patients benefited from combination therapy. CONCLUSION: While the majority of
      Gaucher disease type 1 patients will not need treatment with both substrate
      reduction therapy and enzyme replacement therapy, the current case reports
      demonstrate that judicious use of combination therapy may be of benefit in some
      cases.

PMID- 29373992
TI  - Beyond genomics: understanding exposotypes through metabolomics.
AB  - BACKGROUND: Over the past 20 years, advances in genomic technology have enabled
      unparalleled access to the information contained within the human genome.
      However, the multiple genetic variants associated with various diseases typically
      account for only a small fraction of the disease risk. This may be due to the
      multifactorial nature of disease mechanisms, the strong impact of the
      environment, and the complexity of gene-environment interactions. Metabolomics is
      the quantification of small molecules produced by metabolic processes within a
      biological sample. Metabolomics datasets contain a wealth of information that
      reflect the disease state and are consequent to both genetic variation and
      environment. Thus, metabolomics is being widely adopted for epidemiologic
      research to identify disease risk traits. In this review, we discuss the
      evolution and challenges of metabolomics in epidemiologic research, particularly
      for assessing environmental exposures and providing insights into gene
      environment interactions, and mechanism of biological impact. MAIN TEXT:
      Metabolomics can be used to measure the complex global modulating effect that an
      exposure event has on an individual phenotype. Combining information derived from
      all levels of protein synthesis and subsequent enzymatic action on metabolite
      production can reveal the individual exposotype. We discuss some of the
      methodological and statistical challenges in dealing with this type of high
      dimensional data, such as the impact of study design, analytical biases, and
      biological variance. We show examples of disease risk inference from metabolic
      traits using metabolome-wide association studies. We also evaluate how these
      studies may drive precision medicine approaches, and pharmacogenomics, which have
      up to now been inefficient. Finally, we discuss how to promote transparency and
      open science to improve reproducibility and credibility in metabolomics.
      CONCLUSIONS: Comparison of exposotypes at the human population level may help
      understanding how environmental exposures affect biology at the systems level to
      determine cause, effect, and susceptibilities. Juxtaposition and integration of
      genomics and metabolomics information may offer additional insights. Clinical
      utility of this information for single individuals and populations has yet to be
      routinely demonstrated, but hopefully, recent advances to improve the robustness
      of large-scale metabolomics will facilitate clinical translation.

PMID- 29373995
TI  - Ecology, feeding and natural infection by Leishmania spp. of phlebotomine sand
      flies in an area of high incidence of American tegumentary leishmaniasis in the
      municipality of Rio Branco, Acre, Brazil.
AB  - BACKGROUND: Phlebotomine sand flies (Diptera: Psychodidae) are insects of medical
      importance due to their involvement in the zoonotic transmission of Leishmania
      spp. to vertebrates. The aim of this work was to study the ecology of the sand
      fly fauna of two types of environments, a rural environment (the Transacreana
      Road) and an urban park (Horto Florestal Park), both located in the municipality
      of Rio Branco in the state of Acre, Brazil. Additionally, this study intended to
      investigate Leishmania infection and blood meal sources of these sand flies using
      molecular techniques. METHODS: The sand fly fauna was studied in different
      environments (i.e. forest and peridomestic environments in a rural area, and an
      urban forest) using Shannon traps and HP light traps to collect sand fly
      specimens over 13 consecutive months (December 2014 to January 2016). For
      investigating natural infection by Leishmania and the source of sand fly blood
      meals, DNA samples were extracted from female sand flies and subjected to
      polymerase chain reaction targeting ITS1 and cytb genes. DNA sequencing was
      subsequently used to identify species of Leishmania and the source of blood
      meals. RESULTS: A total of 2515 individual sand flies of 43 species were
      collected and identified, Trichophoromyia auraensis (839; 33.35%),
      Trichophoromyia spp. (537; 21.35%) and Evandromyia saulensis (187; 7.43%) were
      more abundant in the rural area (S = 41 species) than in the urban forest. No
      significant differences were found in species richness between forest and
      peridomestic environments in the rural area (H = 0.04; P > 0.05), but a larger
      number of species was found in the forest. Leishmania DNA was sequenced in 13
      samples, confirming the presence of L. (V.) braziliensis in Th. auraensis (n =
      1), Ev. saulensis (n = 2), Ev. walkeri (n = 1), Ps. llanosmartinsi (n = 1), Pi.
      nevesi (n = 2), Ps. davisi (n = 1), Ps. ayrozai (n = 1), Pa. aragaoi (n = 1), Ny.
      antunesi (n = 1) and Ev. infraspinosa (n = 1). Only Ps. ayrozai possessed a
      sequence similar to that of L. (V.) guyanensis (99%). Through microscopic
      analysis, five specimens of Ev. saulensis were found to possess flagellate forms
      in the hindgut, with an infection rate of 2.4%. Samples from 33 fed females were
      submitted to cytb gene amplification, for which sequencing determined that all
      were similar to the sequence deposited on GenBank for Gallus gallus (domestic
      chicken). CONCLUSIONS: The high abundance of Trichophoromyia auraensis and Ev.
      saulensis, and the detection of L. (V.) braziliensis DNA, suggests that both
      species may be vectors of American tegumentary leishmaniasis. Psychodopygus
      ayrozai was found to be infected by L. (V) braziliesnsis and L. (V.) guyanensis,
      and although collected in low abundance, it may be a potential vector in the
      region. The sand fly fauna was found to be rich and diverse with predominance of
      the genus Psychodopygus. Identification of food sources of fed females showed
      that 100% amplified a gene region compatible with the domestic chicken, which
      although considered refractory in the disease transmission cycle, may have an
      influence on the population dynamics of sand flies.

PMID- 29373997
TI  - Indigenous uses of ethnomedicinal plants among forest-dependent communities of
      Northern Bengal, India.
AB  - BACKGROUND: Traditional knowledge on ethnomedicinal plant is slowly eroding. The
      exploration, identification and documentation on utilization of ethnobotanic
      resources are essential for restoration and preservation of ethnomedicinal
      knowledge about the plants and conservation of these species for greater interest
      of human society. METHODS: The study was conducted at fringe areas of Chilapatta
      Reserve Forest in the foothills of the eastern sub-Himalayan mountain belts of
      West Bengal, India, from December 2014 to May 2016. Purposive sampling method was
      used for selection of area. From this area which is inhabited by aboriginal
      community of Indo-Mongoloid origin, 400 respondents including traditional
      medicinal practitioners were selected randomly for personal interview schedule
      through open-ended questionnaire. The questionnaire covered aspects like plant
      species used as ethnomedicines, plant parts used, procedure for dosage and
      therapy. RESULTS: A total number of 140 ethnomedicinal species was documented, in
      which the tree species (55) dominated the lists followed by herbs (39) and shrubs
      (30). Among these total planted species used for ethnomedicinal purposes, 52
      species were planted, 62 species growing wild or collected from the forest for
      use and 26 species were both wild and planted. The present study documented 61
      more planted species as compared to 17 planted species documented in an
      ethnomedicinal study a decade ago. The documented species were used to treat 58
      human diseases/ailments including nine species used to eight diseases/ailments of
      domestic animals. Stomach-related problems were treated by maximum number of
      plants (40 species) followed by cuts and wounds with 27 plant species and least
      with one species each for 17 diseases or ailments. Maximum number of 12
      diseases/ailments was cured by Melia azedarach followed by Centella asiatica and
      Rauvolfia serpentina which were used to cure 11 diseases/ailments each.
      CONCLUSIONS: The list of 140 plant species indicates that the Chilapatta Reserve
      Forest and its fringe areas are rich in biodiversity of ethnobotanical plant
      species. Rauvolfia serpentina were the most valuable species in terms of its
      maximal use with higher use value. The documentation of 78 species maintained in
      the home gardens indicates the community consciousness on the conservation values
      of these ethnobotanical species. The communities should be encouraged with
      improved cultivation techniques of commercially viable ethnobotanical species
      through capacity building, timely policy intervention along with strong market
      linkage. This will ensure income generation and livelihood improvement and
      ultimate conservation of these species.

PMID- 29373996
TI  - Performance of critical care prognostic scoring systems in low and middle-income
      countries: a systematic review.
AB  - BACKGROUND: Prognostic models-used in critical care medicine for mortality
      predictions, for benchmarking and for illness stratification in clinical trials
      have been validated predominantly in high-income countries. These results may not
      be reproducible in low or middle-income countries (LMICs), not only because of
      different case-mix characteristics but also because of missing predictor
      variables. The study objective was to systematically review literature on the use
      of critical care prognostic models in LMICs and assess their ability to
      discriminate between survivors and non-survivors at hospital discharge of those
      admitted to intensive care units (ICUs), their calibration, their accuracy, and
      the manner in which missing values were handled. METHODS: The PubMed database was
      searched in March 2017 to identify research articles reporting the use and
      performance of prognostic models in the evaluation of mortality in ICUs in LMICs.
      Studies carried out in ICUs in high-income countries or paediatric ICUs and
      studies that evaluated disease-specific scoring systems, were limited to a
      specific disease or single prognostic factor, were published only as abstracts,
      editorials, letters and systematic and narrative reviews or were not in English
      were excluded. RESULTS: Of the 2233 studies retrieved, 473 were searched and 50
      articles reporting 119 models were included. Five articles described the
      development and evaluation of new models, whereas 114 articles externally
      validated Acute Physiology and Chronic Health Evaluation, the Simplified Acute
      Physiology Score and Mortality Probability Models or versions thereof. Missing
      values were only described in 34% of studies; exclusion and or imputation by
      normal values were used. Discrimination, calibration and accuracy were reported
      in 94.0%, 72.4% and 25% respectively. Good discrimination and calibration were
      reported in 88.9% and 58.3% respectively. However, only 10 evaluations that
      reported excellent discrimination also reported good calibration.
      Generalisability of the findings was limited by variability of inclusion and
      exclusion criteria, unavailability of post-ICU outcomes and missing value
      handling. CONCLUSIONS: Robust interpretations regarding the applicability of
      prognostic models are currently hampered by poor adherence to reporting
      guidelines, especially when reporting missing value handling. Performance of
      mortality risk prediction models in LMIC ICUs is at best moderate, especially
      with limitations in calibration. This necessitates continued efforts to develop
      and validate LMIC models with readily available prognostic variables, perhaps
      aided by medical registries.

PMID- 29373998
TI  - Photobiomodulation versus light-emitting diode (LED) therapy in the treatment of
      temporomandibular disorder: study protocol for a randomized, controlled clinical
      trial.
AB  - BACKGROUND: Temporomandibular disorder (TMD) is described as a subgroup of
      orofacial pain with a set of signs and symptoms that involve the
      temporomandibular joint, masticatory muscles, ears, and neck. TMD can occur
      unilaterally or bilaterally and approximately 70% of the population is affected
      with at least one sign. The disorder progresses with orofacial pain, muscle pain
      involving the masticatory and cervical muscles, joint noises (clicks and pops),
      joint block, mandibular dysfunction, and headache. The etiology can be abnormal
      occlusion and/or posture, trauma involving local tissues, repetitive microtrauma,
      parafunctional habits, and an increase in emotional stress. Studies have
      demonstrated that phototherapy is an efficient option for the treatment of TMD,
      leading to improvements in pain and orofacial function. METHODS: The aim of the
      proposed study is to compare the effects of two sources of photobiomodulation in
      individuals with TMD. A randomized, controlled, double-blind, clinical trial is
      proposed, which will involve 80 individuals aged 18-65 years allocated to either
      a laser group or light-emitting diode (LED) group submitted to 12 sessions of
      phototherapy. The Research Diagnostic Criteria for TMDs will be used to evaluate
      all participants. Pain will be measured using the visual analog scale and maximum
      vertical mandibular movement will be determined with the aid of digital calipers.
      DISCUSSION: This study compares the effects of two modalities of laser therapy on
      the pain and orofacial function of patients with TMD dysfunction.
      Photobiomodulation and LED therapy are treatment options for reducing the
      inflammatory process and pain as well as inducing the regeneration of the target
      tissue. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03257748 . Registered on 8
      August 2017.

PMID- 29373999
TI  - Combining 16S rRNA gene variable regions enables high-resolution microbial
      community profiling.
AB  - BACKGROUND: Most of our knowledge about the remarkable microbial diversity on
      Earth comes from sequencing the 16S rRNA gene. The use of next-generation
      sequencing methods has increased sample number and sequencing depth, but the read
      length of the most widely used sequencing platforms today is quite short,
      requiring the researcher to choose a subset of the gene to sequence (typically 16
      33% of the total length). Thus, many bacteria may share the same amplified
      region, and the resolution of profiling is inherently limited. Platforms that
      offer ultra-long read lengths, whole genome shotgun sequencing approaches, and
      computational frameworks formerly suggested by us and by others all allow
      different ways to circumvent this problem yet suffer various shortcomings. There
      is a need for a simple and low-cost 16S rRNA gene-based profiling approach that
      harnesses the short read length to provide a much larger coverage of the gene to
      allow for high resolution, even in harsh conditions of low bacterial biomass and
      fragmented DNA. RESULTS: This manuscript suggests Short MUltiple Regions
      Framework (SMURF), a method to combine sequencing results from different PCR
      amplified regions to provide one coherent profiling. The de facto amplicon length
      is the total length of all amplified regions, thus providing much higher
      resolution compared to current techniques. Computationally, the method solves a
      convex optimization problem that allows extremely fast reconstruction and
      requires only moderate memory. We demonstrate the increase in resolution by in
      silico simulations and by profiling two mock mixtures and real-world biological
      samples. Reanalyzing a mock mixture from the Human Microbiome Project achieved
      about twofold improvement in resolution when combing two independent regions.
      Using a custom set of six primer pairs spanning about 1200 bp (80%) of the 16S
      rRNA gene, we were able to achieve ~ 100-fold improvement in resolution compared
      to a single region, over a mock mixture of common human gut bacterial isolates.
      Finally, the profiling of a Drosophila melanogaster microbiome using the set of
      six primer pairs provided a ~ 100-fold increase in resolution and thus enabling
      efficient downstream analysis. CONCLUSIONS: SMURF enables the identification of
      near full-length 16S rRNA gene sequences in microbial communities, having
      resolution superior compared to current techniques. It may be applied to standard
      sample preparation protocols with very little modifications. SMURF also paves the
      way to high-resolution profiling of low-biomass and fragmented DNA, e.g., in the
      case of formalin-fixed and paraffin-embedded samples, fossil-derived DNA, or DNA
      exposed to other degrading conditions. The approach is not restricted to
      combining amplicons of the 16S rRNA gene and may be applied to any set of
      amplicons, e.g., in multilocus sequence typing (MLST).

PMID- 29374000
TI  - A Breastfeed-Promoting Mobile App Intervention: Usability and Usefulness Study.
AB  - BACKGROUND: Breastfeeding is proven to have lasting health benefits for both
      mothers and infants; however, 6-month exclusive breastfeeding rate remains below
      20% in Thailand. Although the number of research literature and commercial apps
      for breastfeeding women is significantly growing, they are country-specific and
      restricted to English-speaking users. There exists a major knowledge gap on how
      mobile health apps could support breastfeeding in Thailand. To address these
      gaps, MoomMae has been developed with the intention to support Thai women in
      breastfeeding outside of their homes and in keeping their feeding records.
      OBJECTIVE: The aim of this study was to evaluate the usability and usefulness of
      MoomMae, a mobile phone app designed to support breastfeeding women. METHODS: Our
      study was reviewed and approved by Thailand's National Science and Technology
      Development Agency (NSTDA) ethics committee. A total of 21 breastfeeding women
      with at least one Android phone or tablet were recruited via convenience and
      snowball sampling. The study process for each participant was as follows: the
      participant was requested to attend a preuse interview and given the app to use
      for 4 weeks. Following this period, a postuse interview was conducted to examine
      the usability and usefulness of the app. Both sessions were held individually and
      audiorecorded for qualitative analysis. RESULTS: The mean scores of usability and
      usefulness from the postuse survey were 4.33 (SD 0.87; range 1-5) and 4.60 (SD
      0.74; range 2-5). Our qualitative analysis revealed a total of 137 feedbacks: 71
      related to usability and 66 associated with usefulness. A further sentimental
      analysis showed that comments on usability were generally negative (59 negative,
      11 positive, and 1 neutral), and comments on usefulness were relatively positive
      (56 positive, 9 negative, and 1 neutral). We discovered 26 unique design issues
      and proposed recommendations for future improvement. CONCLUSIONS: Our usability
      and usefulness assessment of MoomMae demonstrated that MoomMae has a great
      potential to be a useful self-management tool for breastfeeding mothers in
      Thailand. The qualitative analysis suggested that the app is supportive of
      breastfeeding on demand, but the flow and inputs of the app should be redesigned
      to be more intuitive. For future implementations, the most desirable feature is a
      pump-reminding notification system.

PMID- 29374001
TI  - Effect of a Titanium Tetrafluoride Varnish in the Prevention and Treatment of
      Carious Lesions in the Permanent Teeth of Children Living in a Fluoridated
      Region: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: Titanium tetrafluoride (TiF4) has regained interest due to new
      formulations that have been shown to be more effective against tooth
      demineralization than sodium fluoride (NaF) formulations in vitro and in situ.
      OBJECTIVE: The aim of this study is to evaluate the effect of two types of
      varnishes (4% TiF4 and a commercial 5% NaF) on the prevention of carious lesions
      and the treatment of noncavitated enamel carious lesions in the permanent teeth
      of children living in a fluoridated area. METHODS: This randomized, controlled,
      parallel and single-blind clinical trial involves 63 children, 6-7 years old,
      living in Bauru, Sao Paulo, Brazil. Children were selected according to their
      caries activity (ie, presence of at least 1 tooth with a Nyvad score of 1) and
      randomly divided into the following treatment categories: 4% TiF4 varnish (2.45 %
      F-, pH 1, FGM); 5% NaF varnish (2.26% F-, pH 5, Duraphat, Colgate) and control
      (placebo varnish, pH 5, FGM). The varnishes will be applied on all permanent
      teeth, once a week for 4 weeks and they will be reapplied only once 6 and 12
      months after the study begins. Two calibrated examiners will carry out the
      clinical examination (International Caries Detection and Assessment System
      [ICDAS] and Nyvad indexes, kappa>.8) at baseline, before the first application,
      after the 1st, 6th, 12th, and 18th month of the study begins. Furthermore,
      quantitative fluorescence changes will be measured using Quantitative Light
      Induced Fluorescence (QLF). The degree of patient satisfaction with the treatment
      will also be computed. The data will undergo statistical analysis (P<.05).
      RESULTS: This ongoing study is funded by funding agencies from Brazil (Sao Paulo
      Research Foundation, FAPESP-015/14149-1, and National Council for Scientific and
      Technological Development, CNPq-401313/2016-6). We expect to confirm the efficacy
      of TiF4 on the prevention and treatment of carious lesions by comparing it to NaF
      varnish. The subjects are under 1 month evaluation and the dropout was about 8%.
      No differences between the treatments have been detected at the first month so
      far (P>.05). CONCLUSIONS: If our hypothesis is confirmed, TiF4 varnish can be
      marketed and applied at the individual level and used in community programs to
      control dental caries. TRIAL REGISTRATION: Brazilian Clinical Trials Registry:
      RBR-5VWJ4Y; http://www.ensaiosclinicos.gov.br/rg/?q=RBR-5VWJ4Y (Archived by
      WebCite at http://www.webcitation.org/6wUurEnm7).

PMID- 29374002
TI  - Examining the Frequency and Contribution of Foods Eaten Away From Home in the
      Diets of 18- to 30-Year-Old Australians Using Smartphone Dietary Assessment
      (MYMeals): Protocol for a Cross-Sectional Study.
AB  - BACKGROUND: Young Australians aged between 18 and 30 years have experienced the
      largest increase in the body mass index and spend the largest proportion of their
      food budget on fast food and eating out. Frequent consumption of foods purchased
      and eaten away from home has been linked to poorer diet quality and weight gain.
      There has been no Australian research regarding quantities, type, or the
      frequency of consumption of food prepared outside the home by young adults and
      its impact on their energy and nutrient intakes. OBJECTIVES: The objective of
      this study was to determine the relative contributions of different food outlets
      (eg, fast food chain, independent takeaway food store, coffee shop, etc) to the
      overall food and beverage intake of young adults; to assess the extent to which
      food and beverages consumed away from home contribute to young adults' total
      energy and deleterious nutrient intakes; and to study social and physical
      environmental interactions with consumption patterns of young adults. METHODS: A
      cross-sectional study of 1008 young adults will be conducted. Individuals are
      eligible to participate if they: (1) are aged between 18 and 30 years; (2) reside
      in New South Wales, Australia; (3) own or have access to a smartphone; (4) are
      English-literate; and (5) consume at least one meal, snack, or drink purchased
      outside the home per week. An even spread of gender, age groups (18 to 24 years
      and 25 to 30 years), metropolitan or regional geographical areas, and high and
      low socioeconomic status areas will be included. Participants will record all
      food and drink consumed over 3 consecutive days, together with location purchased
      and consumed in our customized smartphone app named Eat and Track (EaT).
      Participants will then complete an extensive demographics questionnaire. Mean
      intakes of energy, nutrients, and food groups will be calculated along with the
      relative contribution of foods purchased and eaten away from home. A subsample of
      19.84% (200/1008) of the participants will complete three 24-hour recall
      interviews to compare with the data collected using EaT. Data mining techniques
      such as clustering, decision trees, neural networks, and support vector machines
      will be used to build predictive models and identify important patterns. RESULTS:
      Recruitment is underway, and results will be available in 2018. CONCLUSIONS: The
      contribution of foods prepared away from home, in terms of energy, nutrients,
      deleterious nutrients, and food groups to young people's diets will be
      determined, as will the impact on meeting national recommendations. Foods and
      consumption behaviors that should be targeted in future health promotion efforts
      for young adults will be identified.

PMID- 29374003
TI  - Mobile Health Technology Interventions for Suicide Prevention: Protocol for a
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Previous research has reported that two of the major barriers to help
      seeking for individuals at risk of suicide are stigma and geographical isolation.
      Mobile technology offers a potential means of delivering evidence-based
      interventions with greater specificity to the individual, and at the time that it
      is needed. Despite documented motivation by at-risk individuals to use mobile
      technology to track mental health and to support psychological interventions,
      there is a shortfall of outcomes data on the efficacy of mobile health (mHealth)
      technology on suicide-specific outcomes. OBJECTIVE: The objective of this study
      is to develop a protocol for a systematic review and meta-analysis that aims to
      evaluate the effectiveness of mobile technology-based interventions for suicide
      prevention. METHODS: The search includes the Cochrane Central Register of
      Controlled Trials (CENTRAL: The Cochrane Library), MEDLINE, Embase, PsycINFO,
      CRESP and relevant sources of gray literature. Studies that have evaluated
      psychological or nonpsychological interventions delivered via mobile computing
      and communication technology, and have suicidality as an outcome measure will be
      included. Two authors will independently extract data and assess the study
      suitability in accordance with the Cochrane Collaboration Risk of Bias Tool.
      Studies will be included if they measure at least one suicide outcome variable
      (ie, suicidal ideation, suicidal intent, nonsuicidal self-injurious behavior,
      suicidal behavior). Secondary outcomes will be measures of symptoms of
      depression. Where studies are sufficiently homogenous and reported outcomes are
      amenable for pooled synthesis, meta-analysis will be performed. A narrative
      synthesis will be conducted if the data is unsuitable for a meta-analysis.
      RESULTS: The review is in progress, with findings expected by summer 2018.
      CONCLUSIONS: To date, evaluations of mobile technology-based interventions in
      suicide prevention have focused on evaluating content as opposed to efficacy.
      Indeed, previous research has identified mobile applications that appear to
      present harmful content. The current review will address a gap in the literature
      by evaluating the efficacy of stand-alone mobile technology tools in suicide
      prevention. It is imperative that research identifies the evidence base for such
      tools in suicide prevention in order to inform policy, guide clinical practice,
      inform users and focus future research. TRIAL REGISTRATION: PROSPERO
      International Prospective Register of Systematic Reviews CRD42017072899; https://
      www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42017072899  (Archived by
      WebCite at http://www.webcitation.org/ 6tZAj0yqJ).

PMID- 29374004
TI  - eHealth Technologies, Multimorbidity, and the Office Visit: Qualitative Interview
      Study on the Perspectives of Physicians and Nurses.
AB  - BACKGROUND: eHealth is a broad term referring to the application of information
      and communication technologies in the health sector, ranging from health records
      to telemedicine and multiple forms of health education and digital tools. By
      providing increased and anytime access to information, opportunities to exchange
      experiences with others, and self-management support, eHealth has been heralded
      as transformational. It has created a group of informed, engaged, and empowered
      patients as partners, equipped to take part in shared decision making and
      effectively self-manage chronic illness. Less attention has been given to health
      care professionals' (HCPs) experiences of the role of eHealth in patient
      encounters. OBJECTIVE: The objective of this study was to examine HCPs'
      perspectives on how eHealth affects their relationships with patients living with
      multiple chronic conditions, as well as its ethical and practical ramifications.
      METHODS: We interviewed HCPs about their experiences with eHealth and its impact
      on the office visit. Eligible participants needed to report a caseload of >=25%
      of patients with multimorbidity to address issues of managing complex chronic
      conditions and coordination of care. We used a semistructured discussion guide
      for in-depth interviews, and follow-up interviews served to clarify and expand
      upon initial discussions. Constant comparisons and a narrative approach guided
      the analyses, and a relational ethics conceptual lens was applied to the data to
      identify emergent themes. RESULTS: A total of 12 physicians and nurses (6 male, 6
      female; median years of practice=13) participated. eHealth tools most frequently
      described were Web-based educational resources for patients and Web-based
      resources for HCPs such as curated scientific summaries on diagnostic criteria,
      clinical therapies, and dosage calculators. Analysis centered on a grand theme of
      the two-way conversation between HCPs and patients, which addresses a general
      recentering of the ethical relationship between HCPs and patients around
      engagement. Subthemes explain the evolution of the two-way conversation, and
      having, using, and supporting the two-way conversation with patients, primarily
      as this relates to achieving adherence and health outcomes. CONCLUSIONS: Emerging
      ethical concerns were related to the ambiguity of the ideal of empowered patients
      and the ways in which health professionals described enacting those ideals in
      practice, showing how the cultural shift toward truly mutually respectful and
      collaborative practice is in transition. HCPs aim to act in the best interests of
      their patients; the challenge is to benefit from emergent technologies that may
      enhance patient-HCP interactions and effective care, while abiding by
      regulations, dealing with the strictures of the technology itself, and managing
      changing demands on their time.

PMID- 29374005
TI  - Intrapersonal Variation in Goal Setting and Achievement in Health Coaching: Cross
      Sectional Retrospective Analysis.
AB  - BACKGROUND: Chronic conditions in the United States are among the most costly and
      preventable of all health problems. Research suggests health coaching is an
      effective strategy for reducing health risks including decreases in weight, blood
      pressure, lipids, and blood glucose. Much less is known about how and when
      coaching works. OBJECTIVE: The aim of this study was to conduct an analysis of
      intrapersonal variations in participants' progression in health coaching,
      examining gender and age-related differences. METHODS: This was a cross
      sectional, retrospective analysis of 35,333 health coaching participants between
      2012 and 2016. Differences in number of goals and activities set and completed,
      and number of interactions were assessed using negative binomial models.
      Differences in goal type were assessed using logistic regression for gender and
      using the Welch test for age to account for unequal variances. RESULTS:
      Participants choosing online coaching were more likely to be younger and female
      (P<.001). Gender and age differences were found for the types of goals set by
      participants. Regarding program activity, women set and completed 12% more action
      steps than men (P<.001), averaging 21% more interactions than men (P<.001); no
      gender differences were found in number of goals completed (P=.12), although the
      percentage of males and females completing goals was significantly different at
      60 and 120 days postenrollment (P<.001). Results indicated significant age
      related differences in all aspects of program activity: number of interactions,
      goals set and completed, action steps set and completed (all P values <.01), as
      well as significant differences in percentage of individuals completing initial
      goals within 30 days, with older individuals completing more than younger
      individuals did (all P values <.001). CONCLUSIONS: This study found significant
      intrapersonal variation in how people participate in and progress through a
      coaching program. Age-related variations were found in all aspects of coaching
      activity, from modality preference and initial choice of goal type (eg, weight
      management, tobacco cessation) to goal completion, whereas gender-related
      differences were demonstrated for all program activities except number of goals
      set and completed. These findings indicate that to maximize behavior change,
      coaches need to personalize the coaching experience to the individual.

PMID- 29374006
TI  - Web-Based Training Program Using Cognitive Behavioral Therapy to Enhance
      Cognitive Flexibility and Alleviate Psychological Distress Among Schoolteachers:
      Pilot Randomized Controlled Trial.
AB  - BACKGROUND: Schoolteachers are known to be faced with various stresses in their
      work. A simple, less onerous, and effective intervention technique that can
      enhance the stress management skills, particularly, cognitive flexibility, of
      schoolteachers is needed. OBJECTIVE: This study aimed to determine whether stress
      management training using a Web-based cognitive behavioral therapy (CBT) program
      is effective for enhancing the cognitive flexibility of schoolteachers and
      alleviating their subjective distress. METHODS: This study was conducted in a
      random controlled design covering public elementary schoolteachers. Teachers
      allocated to the intervention group received 120 min of group education and
      completed homework using a Web-based CBT program that lasted for 3 months. The
      items of outcome evaluation were cognitive flexibility and subjective distress,
      and the efficacy of intervention was evaluated at 3 months after intervention.
      RESULTS: A total of 240 participants were randomly allocated to the intervention
      group (120 individuals) and the control group (120 individuals). On the basis of
      the principle of intention to treat, the intervention group and the control group
      were compared regarding the amount of change from before intervention to after
      intervention, using a general linear model. Scores of cognitive flexibility and
      subjective distress were significantly more improved in the intervention group
      than in the control group. CONCLUSIONS: The results of this study suggest that
      simple stress management training using a Web-based CBT program in elementary
      schoolteachers enhances cognitive flexibility and alleviates subjective distress.

PMID- 29374007
TI  - A Web-Based Course on Public Health Principles in Disaster and Medical
      Humanitarian Response: Survey Among Students and Faculty.
AB  - BACKGROUND: Web-based public health courses are becoming increasingly popular.
      "Public Health Principles in Disaster and Medical Humanitarian Response" is a
      unique Web-based course in Hong Kong. This course aimed to fill a public health
      training gap by reaching out to postgraduates who are unable to access face-to
      face learning. OBJECTIVE: The aim of this paper was to use a structured framework
      to objectively evaluate the effectiveness of a Web-based course according to
      Greenhalgh et al's quality framework and the Donabedian model to make
      recommendations for program improvement. METHODS: An interim evaluation of the
      first cohort of students in 2014 was conducted according to the Donabedian model
      and a quality framework by Greenhalgh et al using objective and self-reported
      data. RESULTS: Students who registered for the first cohort (n=1152) from June
      16, 2014 to December 15, 2014 (6 months) were surveyed. Two tutors and the course
      director were interviewed. The Web-based course was effective in using technology
      to deliver suitable course materials and assessment and to enhance student
      communication, support, and learning. Of the total number of students registered,
      59.00% (680/1152) were nonlocal, originating from 6 continents, and 72.50%
      (835/1152) possessed a bachelor's or postgraduate degree. The completion rate was
      20.00% (230/1152). The chi-square test comparing students who completed the
      course with dropouts showed no significant difference in gender (P=.40), age
      (P=.98), occupation (P=.43), or qualification (P=.17). The cost (HK $272 per
      student) was lower than that of conducting a face-to-face course (HK $4000 per
      student). CONCLUSIONS: The Web-based course was effective in using technology to
      deliver a suitable course and reaching an intended audience. It had a higher
      completion rate than other Web-based courses. However, sustainable sources of
      funding may be needed to maintain the free Web-based course.

PMID- 29374008
TI  - Helen McShane and colleagues reply to Deborah Cohen.

PMID- 29374009
TI  - Response to: 'Switching from the bio-originators to biosimilar: is it premature
      to recommend this procedure?' by Cantini and Benucci.

PMID- 29374010
TI  - Response to: 'Simultaneous inhibition of alpha4/beta7 integrin and tumor necrosis
      factor-alpha in concomitant spondyloarthritis and inflammatory bowel disease' by
      Richard et al.

PMID- 29374011
TI  - Consider Addison's disease in differential diagnosis of eating disorders in
      children and young people.

PMID- 29374013
TI  - Government postpones first ACOs to allow further consultation.

PMID- 29374014
TI  - Surgeon whose manslaughter conviction was quashed faces GMC hearing.

PMID- 29374015
TI  - Use paracetamol for most acute sore throats, says NICE.

PMID- 29374012
TI  - miR-29 contributes to normal endothelial function and can restore it in
      cardiometabolic disorders.
AB  - We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the
      setting of cardiometabolic disorders represented by type 2 diabetes mellitus
      (T2DM). miR-29 was dysregulated in resistance arterioles obtained by biopsy in
      T2DM patients. Intraluminal delivery of miR-29a-3p or miR-29b-3p mimics restored
      normal endothelium-dependent vasodilation (EDVD) in T2DM arterioles that
      otherwise exhibited impaired EDVD Intraluminal delivery of anti-miR-29b-3p in
      arterioles from non-DM human subjects or rats or targeted mutation of Mir29b-1/a
      gene in rats led to impaired EDVD and exacerbation of hypertension in the rats.
      miR-29b-3p mimic increased, while anti-miR-29b-3p or Mir29b-1/a gene mutation
      decreased, nitric oxide levels in arterioles. The mutation of Mir29b-1/a gene led
      to preferential differential expression of genes related to nitric oxide
      including Lypla1. Lypla1 was a direct target of miR-29 and could abrogate the
      effect of miR-29 in promoting nitric oxide production. Treatment with Lypla1
      siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b-1/a
      mutant rats or treated with anti-miR-29b-3p. These findings indicate miR-29 is
      required for normal endothelial function in humans and animal models and has
      therapeutic potential for cardiometabolic disorders.

PMID- 29374016
TI  - Drug companies are unwilling to share information on trial protocols, study
      finds.

PMID- 29374017
TI  - Alcohol labels should include information on calorie content, public health
      doctors say.

PMID- 29374018
TI  - Enhancer-Driven Gene Expression Changes Facilitate Metastasis.
AB  - Altered enhancer activity allows for dynamic gene expression to promote
      osteosarcoma metastasis.

PMID- 29374019
TI  - Dimerization Is Critical for the Functions of Wild-type and Mutant KRAS.
AB  - Wild-type KRAS increases survival and resistance to MEK inhibitors in KRAS-mutant
      lung cancer cells.

PMID- 29374020
TI  - Blood Monocyte Frequency May Be a Biomarker for Response to Anti-PD-1.
AB  - CD14+CD16-HLA-DRhi monocyte frequency was linked to response to anti-PD-1 in
      patients with melanoma.

PMID- 29374021
TI  - Chromosomal Instability Drives Metastasis Independent of Aneuploidy.
AB  - Chromosomal instability (CIN) promotes metastasis with little effect on primary
      tumor growth.

PMID- 29374022
TI  - Molecular and functional identification of a novel photopigment in Pecten ciliary
      photoreceptors.
AB  - The two basic animal photoreceptor types, ciliary and microvillar, use different
      light-transduction schemes: their photopigments couple to Gt versus Gq proteins,
      respectively, to either mobilize cyclic nucleotides or trigger a lipid signaling
      cascade. A third class of photoreceptors has been described in the dual retina of
      some marine invertebrates; these present a ciliary morphology but operate via
      radically divergent mechanisms, prompting the suggestion that they comprise a
      novel lineage of light sensors. In one of these organisms, an uncommon putative
      opsin was uncovered that was proposed to signal through Go Orthologues
      subsequently emerged in diverse phyla, including mollusks, echinoderms, and
      chordates, but the cells in which they express have not been identified, and no
      studies corroborated their function as visual pigments or their suggested
      signaling mode. Conversely, in only one invertebrate species, Pecten irradians,
      have the ciliary photoreceptors been physiologically characterized, but their
      photopigment has not been identified molecularly. We used the transcriptome of
      Pecten retina to guide the cloning by polymerase chain reaction (PCR) and rapid
      amplification of cDNA ends (RACE) extensions of a new member of this group of
      putative opsins. In situ hybridization shows selective transcription in the
      distal retina, and specific antibodies identify a single band of the expected
      molecular mass in Western blots and distinctly label ciliary photoreceptors in
      retina sections. RNA interference knockdown resulted in a reduction in the early
      receptor current-the first manifestation of light transduction-and prevented the
      prolonged aftercurrent, which requires a large buildup of activated rhodopsin. We
      also obtained a full-length clone of the alpha-subunit of a Go from Pecten retina
      complementary DNA and localized it by in situ hybridization to the distal
      photoreceptors. Small interfering RNA targeting this Go caused a specific
      depression of the photocurrent. These results establish this novel putative opsin
      as a bona fide visual pigment that couples to Go to convey the light signal.

PMID- 29374023
TI  - Miles W Carroll replies to Deborah Cohen.

PMID- 29374024
TI  - Paediatrician convicted of manslaughter must be erased from register, rules High
      Court.

PMID- 29374025
TI  - A 8-year population-based cohort study of irritable bowel syndrome in childhood
      with history of atopic dermatitis.
AB  - Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder
      affecting a large number of people worldwide. Based on the concept of central
      sensitization, we conducted a population-based cohort analysis to investigate the
      risk of IBS in children with atopic dermatitis (AD) as one of the first steps in
      the atopic march. From 2000 to 2007, 1 20 014 children with newly diagnosed AD
      and 1 20 014 randomly selected non-AD controls were included in the study. By the
      end of 2008, incidences of IBS in both cohorts and the AD cohort to non-AD cohort
      hazard ratios (HRs) and CIs were measured. The incidence of IBS during the study
      period was 1.45-fold greater (95% CI: 1.32 to 1.59) in the AD cohort than in the
      non-AD cohort (18.8 vs 12.9 per 10 000 person-years). The AD to non-AD HR of IBS
      was greater for girls (1.60, 95% CI: 1.39 to 1.85) and children>=12 years (1.59,
      95% CI: 1.23 to 2.05). The HR of IBS in AD children increased from 0.84 (95% CI:
      0.75 to 0.94) for those with <=3 AD related visits to 16.7 (95% CI: 14.7 to 18.9)
      for those with >5 visits (P<0.0001, by the trend test). AD children had a greater
      risk of developing IBS. Further research is needed to clarify the role of allergy
      in the pathogenesis of IBS.

PMID- 29374026
TI  - A broad atlas of somatic hypermutation allows prediction of activation-induced
      deaminase targets.
AB  - Activation-induced deaminase (AID) initiates antibody diversification in germinal
      center (GC) B cells through the deamination of cytosines on immunoglobulin genes.
      AID can also target other regions in the genome, triggering mutations or
      chromosome translocations, with major implications for oncogenic transformation.
      However, understanding the specificity of AID has proved extremely challenging.
      We have sequenced at very high depth >1,500 genomic regions from GC B cells and
      identified 275 genes targeted by AID, including 30 of the previously known 35 AID
      targets. We have also identified the most highly mutated hotspot for AID activity
      described to date. Furthermore, integrative analysis of the molecular features of
      mutated genes coupled to machine learning has produced a powerful predictive tool
      for AID targets. We also have found that base excision repair and mismatch repair
      back up each other to faithfully repair AID-induced lesions. Finally, our data
      establish a novel link between AID mutagenic activity and lymphomagenesis.

PMID- 29374028
TI  - Paediatric obesity appears to lower the risk of diabetes if selection bias is
      ignored.
AB  - BACKGROUND: Frustrated with the onslaught of articles reporting fascination with
      results that appear paradoxical but are merely due to selection bias, we studied
      the apparent effect of obesity on diabetes risk in youth who had a test for
      diabetes. We hypothesised that obese subjects would have lower rates of diabetes
      than non-obese subjects due to selection bias, and consequently, obesity would
      appear to lower the risk of diabetes. METHODS: Retrospective cohort study of
      children (4-9 years), pre-teens (10-12 years) and teenagers (13-19 years).
      Participation was restricted to those who had a test of haemoglobin A1C along
      with measured height and weight. Body mass index percentile via the Centers for
      Disease Control and Prevention age and sex standards was calculated and
      categorised. The main outcome was A1C%, subsequently categorised at the level for
      diagnosis of diabetes mellitus (>=6.5%). RESULTS: The sample consisted of 134
      (2%) underweight, 1718 (30%) healthy weight, 660 (12%) overweight and 3190 (56%)
      obese individuals. 16% (n=936) had an A1C>=6.5%. Overall, healthy weight children
      had 8.2 times the risk of A1C>=6.5% (95% CI 5.3 to 12.7) compared with those in
      the obese category. The relative risk was 13 in pre-teens (95% CI 8.5 to 20.0)
      and 3.9 in teenagers (95% CI 3.3 to 4.7). CONCLUSIONS: Healthy weight was
      associated with a 4-13 times higher relative risk of diabetes mellitus compared
      with being obese. While apparently shocking, the study's fatal flaw (selection
      bias) explains the 'paradoxical' finding. Ignoring selection bias can delay
      advances in medical science.

PMID- 29374027
TI  - Initiation of inflammatory tumorigenesis by CTLA4 insufficiency due to type 2
      cytokines.
AB  - Genetically predisposed CTLA4 insufficiency in humans is associated with gastric
      cancer development, which is paradoxical to the prototypical role of CTLA4 in
      suppressing antitumor immunity. CTLA4 is a critical immune checkpoint against
      autoimmune disorders. Autoimmunity has been implicated in protumor or antitumor
      activities. Here, we show that CTLA4 insufficiency initiates de novo
      tumorigenesis in the mouse stomach through inflammation triggered by host
      intrinsic immune dysregulation rather than microbiota, with age-associated
      progression to malignancy accompanied by epigenetic dysregulation. The
      inflammatory tumorigenesis required CD4 T cells, but not the TH1 or TH17 subsets.
      Deficiencies in IL-4 and IL-13 or IL-4 receptor alpha broke the link between
      inflammation and initiation of tumorigenesis. This study establishes the
      causality of CTLA4 insufficiency in gastric cancer and uncovers a role of type 2
      inflammation in initiating gastric epithelial transformation. These findings
      suggest possible improvement of immune therapies by blocking tumorigenic type 2
      inflammation while preserving antitumor type 1 immunity.

PMID- 29374029
TI  - Salt Stress-Induced Loss of Iron Oxidoreduction Activities and Reacquisition of
      That Phenotype Depend on rus Operon Transcription in Acidithiobacillus
      ferridurans.
AB  - The type strain of the mineral-oxidizing acidophilic bacterium Acidithiobacillus
      ferridurans was grown in liquid medium containing elevated concentrations of
      sodium chloride with hydrogen as electron donor. While it became more tolerant to
      chloride, after about 1 year, the salt-stressed acidophile was found to have lost
      its ability to oxidize iron, though not sulfur or hydrogen. Detailed molecular
      examination revealed that this was due to an insertion sequence, ISAfd1, which
      belongs to the ISPepr1 subgroup of the IS4 family, having been inserted
      downstream of the two promoters PI and PII of the rus operon (which codes for the
      iron oxidation pathway in this acidophile), thereby preventing its transcription.
      The ability to oxidize iron was regained on protracted incubation of the culture
      inoculated onto salt-free solid medium containing ferrous iron and incubated
      under hydrogen. Two revertant strains were obtained. In one, the insertion
      sequence ISAfd1 had been excised, leaving an 11-bp signature, while in the other
      an ~2,500-bp insertion sequence (belonging to the IS66 family) was detected in
      the downstream inverted repeat of ISAfd1 The transcriptional start site of the
      rus operon in the second revertant strain was downstream of the two ISs, due to
      the creation of a new "hybrid" promoter. The loss and subsequent regaining of the
      ability of A. ferriduransT to reduce ferric iron were concurrent with those
      observed for ferrous iron oxidation, suggesting that these two traits are closely
      linked in this acidophile.IMPORTANCE Iron-oxidizing acidophilic bacteria have
      primary roles in the oxidative dissolution of sulfide minerals, a process that
      underpins commercial mineral-processing biotechnologies ("biomining"). Most of
      these prokaryotes have relatively low tolerance to chloride, which limits their
      activities when only saline or brackish waters are available. The study showed
      that it was possible to adapt a typical iron-oxidizing acidophile to grow in the
      presence of salt concentrations similar to those in seawater, but in so doing
      they lost their ability to oxidize iron, though not sulfur or hydrogen. The
      bacterium regained its capacity for oxidizing iron when the salt stress was
      removed but simultaneously reverted to tolerating lower concentrations of salt.
      These results suggest that the bacteria that have the main roles in biomining
      operations could survive but become ineffective in cases where saline or brackish
      waters are used for irrigation.

PMID- 29374030
TI  - Microbiome structure influences infection by the parasite Crithidia bombi in
      bumble bees.
AB  - Recent declines in bumble bee populations are of great concern, and have prompted
      critical evaluations of the role of pathogen introductions and host resistance in
      bee health. One factor that may influence host resilience when facing infection
      is the gut microbiota. Previous experiments with Bombus terrestris, a European
      bumble bee, showed that the gut microbiota can protect against Crithidia bombi, a
      widespread trypanosomatid parasite of bumble bees. However, the particular
      characteristics of the microbiome responsible for this protective effect have
      thus far eluded identification. Using wild and commercially-sourced Bombus
      impatiens, an important North American pollinator, we conducted cross-wise
      microbiota transplants to naive hosts of both backgrounds, and challenged them
      with Crithidia As with B. terrestris, we find that microbiota-dependent
      protection against Crithidia operates in B. impatiens Lower Crithidia infection
      loads were experimentally associated with high microbiome diversity, large gut
      bacterial populations, and the presence of Apibacter, Lactobacillus Firm-5, and
      Gilliamella in the gut community. These results indicate that even subtle
      differences between gut community structures can have a significant impact on the
      microbiome's ability to defend against parasite infections.Importance Many wild
      bumble bee populations are under threat by human activity, including through
      introductions of pathogens via commercially-raised bees. Recently, it was found
      that the bumble bee gut microbiota can help defend against a common parasite,
      Crithidia bombi, but the particular factors contributing to this protection are
      unknown. Using both wild and commercially-raised bees, we conduct microbiota
      transplants to show that microbiome diversity, total gut bacterial load, and the
      presence of certain core members of the microbiota may all impact bee
      susceptibility to Crithidia infection. Bee origin (genetic background) was also a
      factor. Finally, by examining this phenomenon in a previously uninvestigated bee
      species, our study demonstrates that microbiome-mediated resistance to Crithidia
      is conserved across multiple bumble bee species. These findings highlight how
      intricate interactions between hosts, microbiomes, and parasites can have wide
      ranging consequences for the health of ecologically important species.

PMID- 29374031
TI  - Bacterial Catabolism of beta-Hydroxypropiovanillone and beta
      Hydroxypropiosyringone Produced in the Reductive Cleavage of Arylglycerol-beta
      Aryl Ether in Lignin.
AB  - Sphingobium sp. strain SYK-6 converts four stereoisomers of arylglycerol-beta
      guaiacyl ether into achiral beta-hydroxypropiovanillone (HPV) via three
      stereospecific reaction steps. Here, we determined the HPV catabolic pathway and
      characterized the HPV catabolic genes involved in the first two steps of the
      pathway. In SYK-6 cells, HPV was oxidized to vanilloyl acetic acid (VAA) via
      vanilloyl acetaldehyde (VAL). The resulting VAA was further converted into
      vanillate through the activation of VAA by coenzyme A. A syringyl-type HPV
      analog, beta-hydroxypropiosyringone (HPS), was also catabolized via the same
      pathway. SLG_12830 (hpvZ), which belongs to the glucose-methanol-choline
      oxidoreductase family, was isolated as the HPV-converting enzyme gene. An hpvZ
      mutant completely lost the ability to convert HPV and HPS, indicating that hpvZ
      is essential for the conversion of both the substrates. HpvZ produced in
      Escherichia coli oxidized both HPV and HPS and other 3-phenyl-1-propanol
      derivatives. HpvZ localized to both the cytoplasm and membrane of SYK-6 and used
      ubiquinone derivatives as electron acceptors. Thirteen gene products of the 23
      aldehyde dehydrogenase (ALDH) genes in SYK-6 were able to oxidize VAL into VAA.
      Mutant analyses suggested that multiple ALDH genes, including SLG_20400,
      contribute to the conversion of VAL. We examined whether the genes encoding
      feruloyl-CoA synthetase (ferA) and feruloyl-CoA hydratase/lyase (ferB and ferB2)
      are involved in the conversion of VAA. Only FerA exhibited activity toward VAA;
      however, disruption of ferA did not affect VAA conversion. These results indicate
      that another enzyme system is involved in VAA conversion.IMPORTANCE Cleavage of
      the beta-aryl ether linkage is the most essential process in lignin
      biodegradation. Although the bacterial beta-aryl ether cleavage pathway and
      catabolic genes have been well documented, there have been no reports regarding
      the catabolism of HPV or HPS, the products of cleavage of beta-aryl ether
      compounds. HPV and HPS have also been found to be obtained from lignin by
      chemoselective catalytic oxidation by 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone/tert-butyl nitrite/O2, followed by cleavage of the beta-aryl ether
      with zinc. Therefore, value-added chemicals are expected to be produced from
      these compounds. In this study, we determined the SYK-6 catabolic pathways for
      HPV and HPS and identified the catabolic genes involved in the first two steps of
      the pathways. Since SYK-6 catabolizes HPV through 2-pyrone-4,6-dicarboxylate,
      which is a building block for functional polymers, characterization of HPV
      catabolism is important not only for understanding the bacterial lignin catabolic
      system but also for lignin utilization.

PMID- 29374032
TI  - Bioavailability of mineral-bound iron to a snow algae-bacteria co-culture and
      implications for albedo-altering snow algae blooms.
AB  - Snow algae can form large-scale blooms across the snowpack surface and near
      surface environments. These pigmented blooms can decrease snow albedo, increase
      local melt rates, and may impact the global heat budget and water cycle. Yet,
      underlying causes for the geospatial occurrence of these blooms remain
      unconstrained. One possible factor contributing to snow algae blooms is the
      presence of mineral dust as a micronutrient source. We investigated the
      bioavailability of iron (Fe) -bearing minerals, including forsterite (Fo90,
      Mg1.8Fe0.2SiO4), goethite, smectite and pyrite as Fe sources for a Chloromonas
      brevispina - bacteria co-culture through laboratory-based experimentation. Fo90
      was capable of stimulating snow algal growth and increased the algal growth rate
      in otherwise Fe-depleted co-cultures. Fo90-bearing systems also exhibited a
      decrease in bacteria:algae ratios compared to Fe-depleted conditions, suggesting
      a shift in microbial community structure. The C. brevispina co-culture also
      increased the rate of Fo90 dissolution relative to an abiotic control. Analysis
      of 16S rRNA genes in the co-culture identified Gammaproteobacteria,
      Betaprotoeobacteria and Sphingobacteria, all of which are commonly found in snow
      and ice environments. Archaea were not detected. Collimonas and Pseudomonas,
      which are known to enhance mineral weathering rates, comprised two of the top
      eight (> 1 %) OTUs. These data provide unequivocal evidence that mineral dust can
      support elevated snow algae growth under otherwise Fe-depleted growth conditions,
      and that snow algae can enhance mineral dissolution under these
      conditions.IMPORTANCE Fe, a key micronutrient for photosynthetic growth, is
      necessary to support the formation of high-density snow algae blooms. The
      laboratory experiments described herein allow for a systematic investigation of
      snow algae-bacteria-mineral interactions and their ability to mobilize and uptake
      mineral-bound Fe. Results provide unequivocal and comprehensive evidence that
      mineral-bound Fe in Fe-bearing Fo90 was bioavailable to Chloromonas brevispina
      snow algae within an algae-bacteria co-culture. This evidence includes: 1) an
      observed increase snow algae density and growth rate; 2) decreased bacteria:algae
      ratios in Fo90-containing cultures relative to cultures grown under similarly Fe
      depleted conditions with no mineral-bound Fe present; and 3) increased Fo90
      dissolution rates in the presence of algae-bacteria co-cultures relative to
      abiotic mineral controls. These results have important implications for the role
      of mineral dust in supplying micronutrients to the snow microbiome, which may
      help support dense snow algae blooms capable of lowering snow albedo, and
      increase snow melt rates on regional, and possibly global, scales.

PMID- 29374033
TI  - Functional Expression of the Clostridium ljungdahlii Acetyl-CoA Synthase in
      Clostridium acetobutylicum as Demonstrated by a Novel In Vivo CO Exchange
      Activity, on the Way to Heterologous Installation of a Functional Wood-Ljungdahl
      Pathway.
AB  - Engineering the Wood-Ljungdahl pathway (WLP) in the established industrial
      organism Clostridium acetobutylicum would allow for the conversion of
      carbohydrates into butanol, acetone, and other metabolites at higher yields than
      is currently possible, while minimizing CO2 and H2 release. To this effect, we
      expressed 11 C. ljungdahlii core genes coding for enzymes and accessory proteins
      of the WLP in C. acetobutylicum The engineered WLP in C. acetobutylicum showed
      functionality of the Eastern branch of the pathway based on the formation of
      labeled 5,10-methylenetetrahydrofolate from 13C-labeled formate, as well as
      functionality of the Western branch as evidenced by the formation of CO from CO2
      However, the lack of labeling in acetate and butyrate pools indicated that the
      connection between the two branches is not functional. The focus of our
      investigation then centered on the functional expression of the acetyl-CoA
      synthase (ACS), which forms a complex with the CO dehydrogenase (CODH) and serves
      to link the two branches of the WLP. The CODH/ACS complex catalyzes the reduction
      of CO2 to CO and the condensation of CO with a methyl-group to form acetyl-CoA,
      respectively. Here we show the simultaneous activities of both recombinant
      enzymes. We demonstrate in vivo, the classical in vitro ACS carbonyl-carbon
      exchange assay, whereby the carbonyl carbon of acetyl-CoA is exchanged with the
      CO carbon. Our data suggest that the low heterologous expression of ACS may limit
      the functionality of the heterologous WLP in C. acetobutylicumIMPORTANCE The
      bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) from C.
      ljungdahlii was heterologously expressed in the obligate heterotroph C.
      acetobutylicum Functional activity of the CODH was confirmed through both the
      oxidation and reduction of CO, as had previously been shown for the heterologous
      CODH from C. carboxidivorans Significantly, a novel in vivo assay for ACS
      exchange activity using 13C tracers was developed and used to confirm functional
      ACS expression.

PMID- 29374034
TI  - Novel method reveals a narrow phylogenetic distribution of bacterial dispersers
      in environmental communities exposed to low hydration conditions.
AB  - In this study, we developed a method that provides community-level surface
      dispersal profiles under controlled hydration conditions from environmental
      samples and enables us to isolate and uncover the diversity of the fastest
      bacterial dispersers. The method expands on the Porous Surface Model (PSM),
      previously used to monitor dispersal of individual bacterial strains in liquid
      films at the surface of a porous ceramic disc. The novel procedure targets
      complex communities and captures the dispersed bacteria on a solid medium for
      growth and detection. The method was first validated by distinguishing motile
      Pseudomonas putida and Flavobacterium johnsoniae strains from their non-motile
      mutants. Applying the method to soil and lake water bacterial communities showed
      that community-scale dispersal declined as conditions became drier. However, for
      both communities, dispersal was detected even under low hydration conditions
      (matric potential: -3.1 kPa), previously proven too dry for P. putida KT2440
      motility. We were then able to specifically recover and characterize the fastest
      dispersers from the inoculated communities. For both soil and lake samples, 16S
      rRNA gene amplicon sequencing revealed that the fastest dispersers were
      substantially less diverse than the total communities. The dispersing fraction of
      the soil microbial community was dominated by Pseudomonas which increased in
      abundance at low hydration conditions, while the dispersing fraction of the lake
      community was dominated by Aeromonas and, under wet conditions (-0.5 kPa), also
      by Exiguobacterium The results gained in this study bring us a step closer to
      assessing the dispersal ability within complex communities under environmentally
      relevant conditions.IMPORTANCE Dispersal is a key process of bacterial community
      assembly. Yet, very few attempts have been made at assessing bacterial dispersal
      at the community level as focus has previously been on pure culture studies. A
      crucial factor for dispersal in habitats where hydration conditions vary, such as
      soils, is the thickness of the liquid films surrounding solid surfaces, but
      little is known on how the ability to disperse in such films varies within
      bacterial communities. Therefore, we developed a method to profile community
      dispersal and identify fast dispersers on a rough surface resembling soil
      surfaces. Our results suggest that within the motile fraction of a bacterial
      community only a minority of the bacterial types are able to disperse in the
      thinnest liquid films. During dry periods, these efficient dispersers can gain a
      significant fitness advantage through their ability to colonize new habitats
      ahead of the rest of the community.

PMID- 29374035
TI  - Functional Characterization of Three Specific Acyl-Coenzyme A Synthetases
      Involved in Anaerobic Cholesterol Degradation in Sterolibacterium denitrificans
      Chol1S.
AB  - The denitrifying betaproteobacterium Sterolibacterium denitrificans Chol1S
      catabolizes steroids such as cholesterol via an oxygen-independent pathway. It
      involves enzyme reaction sequences described for aerobic cholesterol and bile
      acid degradation as well as enzymes uniquely found in anaerobic steroid-degrading
      bacteria. Recent studies provided evidence that in S. denitrificans, the cholest
      4-en-3-one intermediate is oxygen-independently oxidized to Delta4-dafachronic
      acid (C26-oic acid), which is subsequently activated by a substrate-specific acyl
      coenzyme A (acyl-CoA) synthetase (ACS). Further degradation was suggested to
      proceed via unconventional beta-oxidation, where aldolases, aldehyde
      dehydrogenases, and additional ACSs substitute for classical beta-hydroxyacyl-CoA
      dehydrogenases and thiolases. Here, we heterologously expressed three cholesterol
      induced genes that putatively code for AMP-forming ACSs and characterized two of
      the products as specific 3beta-hydroxy-Delta5-cholenoyl-CoA (C24-oic acid)- and
      pregn-4-en-3-one-22-oyl-CoA (C22-oic acid)-forming ACSs, respectively. A third
      heterologously produced ATP-dependent ACS was inactive with C26-, C24-, or C22
      oic-acids but activated 3aalpha-H-4alpha-(3'propanoate)-7abeta-methylhexahydro
      1,5-indanedione (HIP) to HIP-CoA, a rather late intermediate of aerobic
      cholesterol degradation that still contains the CD rings of the sterane skeleton.
      This work provides experimental evidence that anaerobic steroid degradation
      proceeds via numerous alternate CoA-ester-dependent or -independent enzymatic
      reaction sequences as a result of aldolytic side chain and hydrolytic sterane
      ring C-C bond cleavages. The aldolytic side chain degradation pathway comprising
      highly exergonic ACSs and aldehyde dehydrogenases is considered to be essential
      for driving the unfavorable oxygen-independent C26 hydroxylation
      forward.IMPORTANCE The biological degradation of ubiquitously abundant steroids
      is hampered by their low solubility and the presence of two quaternary carbon
      atoms. The degradation of cholesterol by aerobic Actinobacteria has been studied
      in detail for more than 30 years and involves a number of oxygenase-dependent
      reactions. In contrast, much less is known about the oxygen-independent
      degradation of steroids in denitrifying bacteria. In the cholesterol-degrading
      anaerobic model organism Sterolibacterium denitrificans Chol1S, initial evidence
      has been obtained that steroid degradation proceeds via numerous alternate
      coenzyme A (CoA)-ester-dependent/independent reaction sequences. Here, we
      describe the heterologous expression of three highly specific and characteristic
      acyl-CoA synthetases, two of which play key roles in the degradation of the side
      chain, whereas a third one is specifically involved in the B ring degradation.
      The results obtained shed light into oxygen-independent steroid degradation
      comprising more than 40 enzymatic reactions.

PMID- 29374036
TI  - Fate of the Urinary Tract Virus BK Human Polyomavirus in Source-Separated Urine.
AB  - Human polyomaviruses are emerging pathogens that infect a large percentage of the
      human population and are excreted in urine. Consequently, urine that is collected
      for fertilizer production often has high concentrations of polyomavirus genes. We
      studied the fate of infectious double-stranded DNA (dsDNA) BK human polyomavirus
      (BKPyV) in hydrolyzed source-separated urine with infectivity assays and
      quantitative PCR (qPCR). Although BKPyV genomes persisted in the hydrolyzed urine
      for long periods of time (T90 [time required for 90% reduction in infectivity or
      gene copies] of >3 weeks), the viruses were rapidly inactivated (T90 of 1.1 to 11
      h) in most of the tested urine samples. Interestingly, the infectivity of dsDNA
      bacteriophage surrogate T3 (T90 of 24 to 46 days) was much more persistent than
      that of BKPyV, highlighting a major shortcoming of using bacteriophages as human
      virus surrogates. Pasteurization and filtration experiments suggest that BKPyV
      virus inactivation was due to microorganism activity in the source-separated
      urine, and SDS-PAGE Western blots showed that BKPyV protein capsid disassembly is
      concurrent with inactivation. Our results imply that stored urine does not pose a
      substantial risk of BKPyV transmission, that qPCR and infectivity of the dsDNA
      surrogate do not accurately depict BKPyV fate, and that microbial inactivation is
      driven by structural elements of the BKPyV capsid.IMPORTANCE We demonstrate that
      a common urinary tract virus has a high susceptibility to the conditions in
      hydrolyzed urine and consequently would not be a substantial exposure route to
      humans using urine-derived fertilizers. The results have significant implications
      for understanding virus fate. First, by demonstrating that the dsDNA (double
      stranded DNA) genome of the polyomavirus lasts for weeks despite infectivity
      lasting for hours to days, our work highlights the shortcomings of using qPCR to
      estimate risks from unculturable viruses. Second, commonly used dsDNA surrogate
      viruses survived for weeks under the same conditions that BK polyomavirus
      survived for only hours, highlighting issues with using virus surrogates to
      predict how human viruses will behave in the environment. Finally, our
      mechanistic inactivation analysis provides strong evidence that microbial
      activity drives rapid virus inactivation, likely through capsid disassembly.
      Overall, our work underlines how subtle structural differences between viruses
      can greatly impact their environmental fate.

PMID- 29374037
TI  - Whole-Genome Sequencing and Genetic Analysis Reveal Novel Stress Responses to
      Individual Constituents of Essential Oils in Escherichia coli.
AB  - Food preservation by the use of essential oils (EOs) is being extensively studied
      because of the antimicrobial properties of their individual constituents (ICs).
      Three resistant mutants (termed CAR, CIT, and LIM) of Escherichia coli MG1655
      were selected by subculturing with the ICs carvacrol, citral, and (+)-limonene
      oxide, respectively. These derivative strains showed increased MIC values of ICs
      and concomitantly enhanced resistance to various antibiotics (ampicillin,
      trimethoprim, chloramphenicol, tetracycline, kanamycin, novobiocin, norfloxacin,
      cephalexin, and nalidixic acid) compared to those for the parental strain (wild
      type [WT]). Whole-genome sequencing (WGS) of these hyperresistant strains
      permitted the identification of single nucleotide polymorphisms (SNPs) and
      deletions in comparison to the WT. In order to analyze the contribution of these
      mutations to the increased antimicrobial resistance detected in hyperresistant
      strains, derivative strains were constructed by allelic reversion. A role of the
      SoxR D137Y missense mutation in CAR was confirmed by growth in the presence of
      some ICs and antibiotics and by its tolerance to ICs but not to lethal heat
      treatments. In CIT, increased resistance relied on contributions by several
      detected SNPs, resulting in a frameshift in MarR and an in-frame GyrB DeltaG157
      mutation. Finally, both the insertion resulting in an AcrR frameshift and large
      chromosomal deletions found in LIM were correlated with the hyperresistant
      phenotype of this strain. The nature of the obtained mutants suggests intriguing
      links to cellular defense mechanisms previously implicated in antibiotic
      resistance.IMPORTANCE The antimicrobial efficacy of ICs has been proven over the
      years, together with their potential to improve traditional heat treatments by
      reducing treatment intensity and, consequently, adverse effects on food quality.
      However, the mechanisms of bacterial inactivation by ICs are still not well
      understood, in contrast to antibiotics. We performed WGS of three E. coli strains
      that are hyperresistant to ICs. The information provided detailed insight into
      the mechanisms of bacterial resistance arising from exposure to carvacrol,
      citral, and (+)-limonene oxide. Future experiments will undoubtedly yield
      additional insights into genes and pathways contributing to the acquisition of
      endogenous resistance to ICs.

PMID- 29374038
TI  - Methanogens Are Major Contributors to Nitrogen Fixation in Soils of the Florida
      Everglades.
AB  - The objective of this study was to investigate the interaction of the nitrogen
      (N) cycle with methane production in the Florida Everglades, a large freshwater
      wetland. This study provides an initial analysis of the distribution and
      expression of N-cycling genes in Water Conservation Area 2A (WCA-2A), a section
      of the marsh that underwent phosphorus (P) loading for many years due to runoff
      from upstream agricultural activities. The elevated P resulted in increased
      primary productivity and an N limitation in P-enriched areas. Results from
      quantitative real-time PCR (qPCR) analyses indicated that the N cycle in WCA-2A
      was dominated by nifH and nirK/S, with an increasing trend in copy numbers in P
      impacted sites. Many nifH sequences (6 to 44% of the total) and nifH transcript
      sequences (2 to 49%) clustered with the methanogenic Euryarchaeota, in stark
      contrast to the proportion of core gene sequences representing Archaea (<=0.27%
      of SSU rRNA genes) for the WCA-2A microbiota. Notably, archaeal nifH gene
      transcripts were detected at all sites and comprised a significant proportion of
      total nifH transcripts obtained from the unimpacted site, indicating that
      methanogens are actively fixing N2 Laboratory incubations with soils taken from
      WCA-2A produced nifH transcripts with the production of methane from H2 plus CO2
      and acetate as electron donors and carbon sources. Methanogenic N2 fixation is
      likely to be an important, although largely unrecognized, route through which
      fixed nitrogen enters the anoxic soils of the Everglades and may have significant
      relevance regarding methane production in wetlands.IMPORTANCE Wetlands are the
      most important natural sources of the greenhouse gas methane, and much of that
      methane emanates from (sub)tropical peatlands. Primary productivity in these
      peatlands is frequently limited by the availability of nitrogen or phosphorus;
      however, the response to nutrient limitations of microbial communities that
      control biogeochemical cycling critical to ecosystem function may be complex and
      may be associated with a range of processes, including methane production. We
      show that many, if not most, of the methanogens in the peatlands of the Florida
      Everglades possess the nifH gene and actively express it for N2 fixation coupled
      with methanogenesis. These findings indicate that archaeal N2 fixation would play
      crucial role in methane emissions and overall N cycle in subtropical wetlands
      suffering N limitation.

PMID- 29374039
TI  - Novel Cell Wall Hydrolase CwlC from Bacillus thuringiensis Is Essential for
      Mother Cell Lysis.
AB  - In this study, a sporulation-specific gene (tentatively named cwlC) involved in
      mother cell lysis in Bacillus thuringiensis was characterized. The encoded CwlC
      protein consists of an N-terminal N-acetylmuramoyl-l-alanine amidase (MurNAc-LAA)
      domain and a C-terminal amidase02 domain. The recombinant histidine-tagged CwlC
      proteins purified from Escherichia coli were able to directly bind to and digest
      the B. thuringiensis cell wall. The CwlC point mutations at the two conserved
      glutamic acid residues (Glu-24 and Glu-140) shown to be critical for the
      catalytic activity in homologous amidases resulted in a complete loss of cell
      wall lytic activity, suggesting that CwlC is an N-acetylmuramoyl-l-alanine
      amidase. Results of transcriptional analyses indicated that cwlC is transcribed
      as a monocistronic unit and that its expression is dependent on sporulation sigma
      factor K (sigmaK). Deletion of cwlC completely blocked mother cell lysis during
      sporulation without impacting the sporulation frequency, Cry1Ac protein
      production, and insecticidal activity. Taken together, our data suggest that CwlC
      is an essential cell wall hydrolase for B. thuringiensis mother cell lysis during
      sporulation. Engineered B. thuringiensis strains targeting cwlC, which allows the
      crystal inclusion to remain encapsulated in the mother cell at the end of
      sporulation, may have the potential to become more effective biological control
      agents in agricultural applications since the crystal inclusion remains
      encapsulated in the mother cell at the end of sporulation.IMPORTANCE Mother cell
      lysis has been well studied in Bacillus subtilis, which involves three distinct
      yet functionally complementary cell wall hydrolases. In this study, a novel cell
      wall hydrolase, CwlC, was investigated and found to be essential for mother cell
      lysis in Bacillus thuringiensis CwlC of B. thuringiensis only shows 9 and 21%
      sequence identity with known B. subtilis mother cell hydrolases CwlB and CwlC,
      respectively, suggesting that mechanisms of mother cell lysis may differ between
      B. subtilis and B. thuringiensis The cwlC gene deletion completely blocked the
      release of spores and crystals from the mother cell without affecting
      insecticidal activity. This may provide a new effective strategy for crystal
      encapsulation against UV light inactivation.

PMID- 29374040
TI  - Deterioration-Associated Microbiome of Stone Monuments: Structure, Variation, and
      Assembly.
AB  - Research on the microbial communities that colonize stone monuments may provide a
      new understanding of stone biodeterioration and microbe-induced carbonate
      precipitation. This work investigated the seasonal variation of microbial
      communities in 2016 and 2017, as well as its effects on stone monuments. We
      determined the bacterial and fungal compositions of 12 samples from four well
      separated geographic locations by using 16S rRNA and internal transcribed spacer
      gene amplicon sequencing. Cyanobacteria and Ascomycota were the predominant
      bacterial and fungal phyla, respectively, and differences in species abundance
      among our 12 samples and 2 years showed no consistent temporal or spatial trends.
      Alpha diversity, estimated by Shannon and Simpson indices, revealed that an
      increase or decrease in bacterial diversity corresponded to a decrease or
      increase in the fungal community from 2016 to 2017. Large-scale association
      analysis identified potential bacteria and fungi correlated with stone
      deterioration. Functional prediction revealed specific pathways and microbiota
      associated with stone deterioration. Moreover, a culture-dependent technique was
      used to identify microbial isolates involved in biodeterioration and
      carbonatogenesis; 64% of 85 bacterial isolates caused precipitation of carbonates
      in biomineralization assays. Imaging techniques including scanning electron
      microscopy with energy-dispersive spectroscopy, X-ray diffraction, and
      fluorescence imaging identified CaCO3 crystals as calcite and vaterite. Although
      CaCO3 precipitation induced by bacteria often has esthetically deleterious
      impacts on stone monuments, this process may potentially serve as a novel,
      environmentally friendly bacterial self-inoculation approach to the conservation
      of stone.IMPORTANCE Comprehensive analyses of the microbiomes associated with the
      deterioration of stone monuments may contribute to the understanding of
      mechanisms of deterioration, as well as to the identification of potentially
      beneficial or undesirable microbial communities and their genomic pathways. In
      our study, we demonstrated that Cyanobacteria was the predominant bacterial
      phylum and exhibited an increase from 2016 to 2017, while Proteobacteria showed a
      decreasing trend. Apart from esthetic deterioration caused by cyanobacteria and
      fungi, white plaque, which is composed mainly of CaCO3 and is probably induced by
      Crossiella and Cyanobacteria, was also considered to be another threat to stone
      monuments. We showed that there was no significant correlation between microbial
      population variation and geographic location. Specific functional genes and
      pathways were also enriched in particular bacterial species. The CaCO3
      precipitation induced by an indigenous community of carbonatogenic bacteria also
      provides a self-inoculation approach for the conservation of stone.

PMID- 29374041
TI  - The Babesia divergens Asia Lineage Is Maintained through Enzootic Cycles between
      Ixodes persulcatus and Sika Deer in Hokkaido, Japan.
AB  - Parasites of the Babesiadivergens Asia lineage, which are closely related to B.
      divergens in Europe and Babesia sp. strain MO1 in the United States, were
      recently reported in sika deer (Cervus nippon) in eastern Japan. To identify the
      tick vector(s) for this parasite, we conducted a field survey in Hokkaido, Japan,
      where the infection rate in sika deer is the highest in the country. A specific
      PCR system which detects and discriminates between lineages within B. divergens
      and between those lineages and Babesia venatorum showed that Ixodes persulcatus
      (11/822), but not sympatric Ixodes ovatus (0/595) or Haemaphysalis sp. (0/163)
      ticks, carried B. divergens Asia lineage. Genomic DNA was archived from salivary
      glands of partially engorged I. persulcatus females and three isolates of B.
      divergens Asia lineage were newly described. The 18S rRNA gene sequence of the
      isolates formed the Asia lineage cluster with those previously described in sika
      deer isolates. One salivary gland also contained parasites of Babesia microti
      U.S. lineage, which were subsequently isolated in a hamster in vivoB. venatorum
      (strain Etb5) was also detected in one I. persulcatus tick. The 18S rRNA sequence
      of Etb5 was 99.7% identical to that of B. venatorum (AY046575) and was
      phylogenetically positioned in a taxon composed of B. venatorum isolates from
      Europe, China, and Russia. The geographical distribution of I. persulcatus is
      consistent with that of B. divergens in sika deer in Japan. These results suggest
      that I. persulcatus is a principal vector for B. divergens in Japan and Eurasia,
      where I. persulcatus is predominantly distributed.IMPORTANCE The Babesiadivergens
      Asia lineage of parasites closely related to B. divergens in Europe and Babesia
      sp. MO1 in the United States was recently reported in Cervus nippon in eastern
      Japan. In this study, specific PCR for the Asia lineage identified 11 positives
      in 822 host-seeking Ixodes persulcatus ticks, a principal vector for many tick
      borne disease agents. Gene sequences of three isolates obtained from DNA in
      salivary glands of female ticks were identical to each other and to those in C.
      nippon We also demonstrate the coinfection of B. divergens Asia lineage with
      Babesia microti U.S. lineage in a tick salivary gland and, furthermore, isolated
      the latter in a hamster. These results suggest that I. persulcatus is the
      principal vector for B. divergens as well as for B. microti, and both parasites
      may be occasionally cotransmitted by I. persulcatus This report will be important
      for public health, since infection may occur through transfusion.

PMID- 29374042
TI  - Genome Analysis of Fimbriiglobus ruber SP5T, a Planctomycete with Confirmed
      Chitinolytic Capability.
AB  - Members of the bacterial order Planctomycetales have often been observed in
      associations with Crustacea. The ability to degrade chitin, however, has never
      been reported for any of the cultured planctomycetes although utilization of N
      acetylglucosamine (GlcNAc) as a sole carbon and nitrogen source is well
      recognized for these bacteria. Here, we demonstrate the chitinolytic capability
      of a member of the family Gemmataceae, Fimbriiglobus ruber SP5T, which was
      isolated from a peat bog. As revealed by metatranscriptomic analysis of chitin
      amended peat, the pool of 16S rRNA reads from F. ruber increased in response to
      chitin availability. Strain SP5T displayed only weak growth on amorphous chitin
      as a sole source of carbon but grew well with chitin as a source of nitrogen. The
      genome of F. ruber SP5T is 12.364 Mb in size and is the largest among all
      currently determined planctomycete genomes. It encodes several enzymes putatively
      involved in chitin degradation, including two chitinases affiliated with the
      glycoside hydrolase (GH) family GH18, GH20 family beta-N-acetylglucosaminidase,
      and the complete set of enzymes required for utilization of GlcNAc. The gene
      encoding one of the predicted chitinases was expressed in Escherichia coli, and
      the endochitinase activity of the recombinant enzyme was confirmed. The genome
      also contains genes required for the assembly of type IV pili, which may be used
      to adhere to chitin and possibly other biopolymers. The ability to use chitin as
      a source of nitrogen is of special importance for planctomycetes that inhabit N
      depleted ombrotrophic wetlands.IMPORTANCE Planctomycetes represent an important
      part of the microbial community in Sphagnum-dominated peatlands, but their
      potential functions in these ecosystems remain poorly understood. This study
      reports the presence of chitinolytic potential in one of the recently described
      peat-inhabiting members of the family Gemmataceae, Fimbriiglobus ruber SP5T This
      planctomycete uses chitin, a major constituent of fungal cell walls and
      exoskeletons of peat-inhabiting arthropods, as a source of nitrogen in N-depleted
      ombrotrophic Sphagnum-dominated peatlands. This study reports the chitin
      degrading capability of representatives of the order Planctomycetales.

PMID- 29374043
TI  - Targeting Bacteria and Methanogens To Understand the Role of Residual Slurry as
      an Inoculant in Stored Liquid Dairy Manure.
AB  - Microbial communities in residual slurry left after removal of stored liquid
      dairy manure have been presumed to increase methane emission during new storage,
      but these microbes have not been studied. While actual manure storage tanks are
      filled gradually, pilot- and farm-scale studies on methane emissions from such
      systems often use a batch approach. In this study, six pilot-scale outdoor
      storage tanks with (10% and 20%) and without residual slurry were filled
      (gradually or in batch) with fresh dairy manure, and methane and methanogenic and
      bacterial communities were studied during 120 days of storage. Regardless of
      filling type, increased residual slurry levels resulted in higher abundance of
      methanogens and bacteria after 65 days of storage. However, stronger correlation
      between methanogen abundance and methane flux was observed in gradually filled
      tanks. Despite some variations in the diversity of methanogens or bacteria with
      the presence of residual slurry, core phylotypes were not impacted. In all
      samples, the phylum Firmicutes predominated (~57 to 70%) bacteria: >90% were
      members of ClostridiaMethanocorpusculum dominated (~57 to 88%) archaeal
      phylotypes, while Methanosarcina gradually increased with storage time. During
      peak flux of methane, Methanosarcina was the major player in methane production.
      The results suggest that increased levels of residual slurry have little impact
      on the dominant methanogenic or bacterial phylotypes, but large population sizes
      of these organisms may result in increased methane flux during the initial phases
      of storage.IMPORTANCE Methane is the major greenhouse gas emitted from stored
      liquid dairy manure. Residual slurry left after removal of stored manure from
      tanks has been implicated in increasing methane emissions in new storages, and
      well-adapted microbial communities in it are the drivers of the increase. Linking
      methane flux to the abundance, diversity, and activity of microbial communities
      in stored slurries with different levels of residual slurry can help to improve
      the mitigation strategy. Mesoscale and lab-scale studies conducted so far on
      methane flux from manure storage systems used batch-filled tanks, while the
      actual condition in many farms involves gradual filling. Hence, this study
      provides important information toward determining levels of residual slurry that
      result in significant reduction of well-adapted microbial communities prior to
      storage, thereby reducing methane emissions from manure storage tanks filled
      under farm conditions.

PMID- 29374044
TI  - Inhibitory Effect of Vascular Endothelial Growth Factor on the Slowly Activating
      Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) exerts a number of
      beneficial effects on ischemic myocardium via its angiogenic properties. However,
      little is known about whether VEGF has a direct effect on the electrical
      properties of cardiomyocytes. In the present study, we investigated the effects
      of different concentrations of VEGF on delayed rectifier potassium currents (IK)
      in guinea pig ventricular myocytes and their effects on action potential (AP)
      parameters. METHODS AND RESULTS: IK and AP were recorded by the whole-cell patch
      clamp method in ventricular myocytes. Cells were superfused with control solution
      or solution containing VEGF at different concentrations for 10 minutes before
      recording. Some ventricular myocytes were pretreated with a phosphatidylinositol
      3-kinase inhibitor for 1 hour before the addition of VEGF. We found that VEGF
      inhibited the slowly activating delayed rectifier potassium current (IKs) in a
      concentration-dependent manner (18.13+/-1.04 versus 12.73+/-0.34, n=5, P=0.001;
      12.73+/-0.34 versus 9.05+/-1.20, n=5, P=0.036) and prolonged AP duration (894.5+/
      36.92 versus 746.3+/-33.71, n=5, P=0.021). Wortmannin, a phosphatidylinositol 3
      kinase inhibitor, eliminated these VEGF-induced effects. VEGF had no significant
      effect on the rapidly activating delayed rectifier potassium current (IKr),
      resting membrane potential, AP amplitude, or maximal velocity of depolarization.
      CONCLUSIONS: VEGF inhibited IKs in a concentration-dependent manner through a
      phosphatidylinositol 3-kinase-mediated signaling pathway, leading to AP
      prolongation. The results indicate a promising therapeutic potential of VEGF in
      prevention of ventricular tachyarrhythmias under conditions of high sympathetic
      activity and ischemia.

PMID- 29374045
TI  - More, More, More: Reducing Thrombosis in Acute Coronary Syndromes Beyond Dual
      Antiplatelet Therapy-Current Data and Future Directions.

PMID- 29374046
TI  - Comparison of Prevalence, Awareness, Treatment, and Control of Cardiovascular
      Risk Factors in China and the United States.
AB  - BACKGROUND: The reasons for China's high stroke prevalence are not well
      understood. The cardiovascular risk factor profiles of China and the United
      States have not been directly compared in nationally representative population
      samples. METHODS AND RESULTS: Using data from the CHARLS (China Health and
      Retirement Longitudinal Study) and the NHANES (US National Health and Nutrition
      Examination Survey), we compared cardiovascular risk factors from 2011 to 2012
      among people aged 45 to 75 years between the 2 countries (China, 12 654 people;
      United States, 2607 people): blood pressure, cholesterol, body mass index, waist
      circumference, fasting plasma glucose, hemoglobin A1c, and high-sensitivity C
      reactive protein. Compared with the United States, China had a lower prevalence
      of hypertension but a higher mean blood pressure and a higher proportion of
      patients with severe hypertension (>=160/100 mm Hg) (10.5% versus 4.5%). China
      had substantially lower rates of hypertension treatment (46.8% versus 77.9%) and
      control (20.3% versus 54.7%). Dyslipidemia was less common in China, but lipid
      levels were not significantly different because dyslipidemia awareness and
      control rates in China were 3- and 7-fold lower than US rates, respectively. High
      sensitivity C-reactive protein, body mass index, and waist circumference were
      significantly lower in China than in the United States. Clustering of
      hypertension with other cardiovascular risk factors was more common in China.
      CONCLUSIONS: Hypertension is more common in the United States, but blood pressure
      levels are higher in China, which may be responsible for China's high stroke
      prevalence. The low rates of awareness, treatment, and control of hypertension
      provide an exceptional opportunity for China to reduce risk in its population.

PMID- 29374047
TI  - Use of Direct Oral Anticoagulants in Canadian Primary Care Practice 2010-2015: A
      Cohort Study From the Canadian Primary Care Sentinel Surveillance Network.
AB  - BACKGROUND: As questions have been raised about the appropriateness of direct
      oral anticoagulant (DOAC) dosing among outpatients with atrial fibrillation, we
      examined this issue in patients being managed by primary care providers. METHODS
      AND RESULTS: This was a retrospective cohort new-user study using electronic
      medical records from 744 Canadian primary care clinicians. Potentially
      inappropriate DOAC prescribing was defined as prescribing lower or higher doses
      than those recommended by guidelines for patients with nonvalvular atrial
      fibrillation. Of the 6658 patients with nonvalvular atrial fibrillation who were
      prescribed a DOAC (mean age: 74.8; 55% male), 626 (9.4%) had a CHADS2 score of 0,
      and 168 (2.5%) had a CHADS-VASc score of 0. Of the DOAC prescriptions, 527 (7.7%)
      were deemed potentially inappropriate: 496 (7.2%) were potentially underdosed,
      and 31 (0.5%) were prescribed a dose that was higher than recommended. Patients
      were more likely to be prescribed lower-than-recommended doses if they were
      female (adjusted odds ratio [aOR]: 1.3 [95% confidence interval (CI), 1.0-1.5]),
      had multiple comorbidities (aOR: 1.4 [95% CI, 1.1-1.8])-particularly heart
      failure (aOR: 1.6 [95% CI, 1.2-2.0]) or dementia (aOR: 1.4 [95% CI, 1.1-1.8])-or
      if they were also taking aspirin (aOR: 1.7 [95% CI, 1.3-2.1]) or nonsteroidal
      anti-inflammatory drugs (aOR: 1.2 [95% CI, 1.02-1.5]). Potentially inappropriate
      DOAC dosing was more common in rural practices (aOR: 2.1 [95% CI, 1.7-2.6]) or
      smaller practices (aOR: 1.9 [95% CI, 1.6-2.4] for practices smaller than median).
      CONCLUSIONS: The vast majority of DOAC prescriptions in our cohort of primary
      care-managed patients appeared to be for appropriate doses, particularly since
      prescribing a reduced dose of DOAC may be appropriate in frail patients or those
      taking other medications that predispose to bleeding.

PMID- 29374048
TI  - Arachidonic Acid, but Not Omega-3 Index, Relates to the Prevalence and
      Progression of Abdominal Aortic Aneurysm in a Population-Based Study of Danish
      Men.
AB  - BACKGROUND: Animal models support dietary omega-3 fatty acids protection against
      abdominal aortic aneurysm (AAA), but clinical data are scarce. The sum of red
      blood cell proportions of the omega-3 eicosapentaenoic and docosahexaenoic acids,
      known as omega-3 index, is a valid surrogate for long-term omega-3 intake. We
      investigated the association between the omega-3 index and the prevalence and
      progression of AAA. We also investigated associations between AAA and arachidonic
      acid, an omega-6 fatty acid that is a substrate for proinflammatory lipid
      mediators. METHODS AND RESULTS: We obtained blood samples from 498 AAA patients
      (maximal aortic diameter >=30 mm) within a population-based ultrasound-screening
      trial in men and from 199 age-matched controls who screened negative. We
      determined the fatty acids of red blood cells by gas chromatography. During a
      median follow-up of 4.85 years, 141 AAA patients reached criteria for vascular
      surgical repair. Participants were high consumers of omega-3 (average omega-3
      index: 7.6%). No significant associations were found for omega-3 index. In
      contrast, arachidonic acid in AAA patients was higher than in controls (P<0.001),
      and individuals in the upper tertile of arachidonic acid at baseline had higher
      probability of having AAA (odds ratio: 1.309; 95% confidence interval, 1.021
      1.678; P=0.033). AAA patients at the upper tertile of arachidonic acid at
      baseline had a 54% higher risk of needing surgical repair during follow-up
      (hazard ratio: 1.544; 95% confidence interval, 1.127-2.114; P=0.007).
      CONCLUSIONS: Omega-3 index is unrelated to men with AAA from a country in which
      fish consumption is customarily high. Arachidonic acid is associated with AAA
      presence and progression. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT00662480.

PMID- 29374050
TI  - Is THIS the way to better improvement?

PMID- 29374051
TI  - Small-Cell Neuroendocrine Tumors: Cell State Trumps the Oncogenic Driver.
AB  - Small-cell neuroendocrine cancers often originate in the lung but can also arise
      in the bladder or prostate. Phenotypically, small-cell carcinoma of the bladder
      (SCCB) shares many similarities with small-cell lung cancer (SCLC). It is unknown
      whether SCCB and SCLC share common genetic driver mutations. Clin Cancer Res;
      24(8); 1775-6. (c)2018 AACRSee related article by Chang et al., p. 1965.

PMID- 29374052
TI  - The Strategy of PIKing a Target: What Is AKTually Most Effective?
AB  - Breast and gynecologic cancers harboring PIK3CA mutations showed no significant
      responses to AZD5363, a pan-AKT catalytic inhibitor, in contrast with previous in
      vitro data showing activity of the drug in this subset of cancers. These results
      raise the question of how to select the most accurate predictive biomarkers of
      response. Clin Cancer Res; 24(9); 2029-31. (c)2018 AACRSee related article by
      Banerji et al., p. 2050.

PMID- 29374049
TI  - Evidence Gaps in the Era of Non-Vitamin K Oral Anticoagulants.

PMID- 29374053
TI  - Wide Expression and Significance of Alternative Immune Checkpoint Molecules, B7x
      and HHLA2, in PD-L1-Negative Human Lung Cancers.
AB  - Purpose: Immunotherapy targeting the PD-1/PD-L1 pathway has changed the treatment
      landscape of non-small cell lung carcinoma (NSCLC). We demonstrated that HHLA2, a
      newly identified immune inhibitory molecule, was widely expressed in NSCLC. We
      now compared the expression and function of PD-L1 with alternative immune
      checkpoints, B7x and HHLA2.Experimental Design: Expression was examined in tissue
      microarrays consisting of 392 resected NSCLC tumors. Effects of PD-L1, B7x, and
      HHLA2 on human T-cell proliferation and cytokine production were
      investigated.Results: PD-L1 expression was identified in 25% and 31% of tumors in
      the discovery and validation cohorts and was associated with higher stage and
      lymph node involvement. The multivariate analysis showed that stage, TIL status,
      and lymph node involvement were independently associated with PD-L1 expression.
      B7x was expressed in 69% and 68%, whereas HHLA2 was positive in 61% and 64% of
      tumors in the two sets. The coexpression of PD-L1 with B7x or HHLA2 was
      infrequent, 6% and 3%. The majority (78%) of PD-L1-negative cases expressed B7x,
      HHLA2, or both. The triple-positive group had more TIL infiltration than the
      triple-negative group. B7x-Ig and HHLA2-Ig inhibited TCR-mediated proliferation
      of CD4 and CD8 T cells more robustly than PD-L1-Ig. All three significantly
      suppressed cytokine productions by T cells.Conclusions: The majority of PD-L1
      negative lung cancers express alternative immune checkpoints. The roles of the
      B7x and HHLA2 pathway in mediating immune evasion in PD-L1-negative tumors
      deserve to be explored to provide the rationale for an effective immunotherapy
      strategy in these tumors. Clin Cancer Res; 24(8); 1954-64. (c)2018 AACR.

PMID- 29374054
TI  - Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in
      High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC
      Study.
AB  - Purpose: Adjuvant sunitinib therapy compared with placebo prolonged disease-free
      survival (DFS) in patients with locoregional high-risk renal cell carcinoma (RCC)
      in the S-TRAC trial (ClinicalTrials.gov number NCT00375674). A prospectively
      designed exploratory analysis of tissue biomarkers was conducted to identify
      predictors of treatment benefit.Experimental Design: Tissue blocks were used for
      immunohistochemistry (IHC) staining of programmed cell death ligand 1 (PD-L1),
      CD4, CD8, and CD68. DFS was compared between < versus >= median IHC parameter
      using the Kaplan-Meier method. For biomarkers with predictive potential, receiver
      operating characteristics curves were generated.Results: Baseline characteristics
      were similar in patients with (n = 191) and without (n = 419) IHC analysis. Among
      patients with IHC, longer DFS was observed in patients with tumor CD8+ T-cell
      density >= versus < median [median (95% CI), not reached (6.83-not reached)
      versus 3.47 years (1.73-not reached); hazard ratio (HR) 0.40 (95% CI, 0.20-0.81);
      P = 0.009] treated with sunitinib (n = 101), but not with placebo (n = 90). The
      sensitivity and specificity for CD8+ T-cell density in predicting DFS were 0.604
      and 0.658, respectively. Shorter DFS was observed in placebo-treated patients
      with PD-L1+ versus PD-L1- tumors (HR 1.75; P = 0.103). Among all patients with PD
      L1+ tumors, DFS was numerically longer with sunitinib versus placebo (HR 0.58; P
      = 0.175).Conclusions: Greater CD8+ T-cell density in tumor tissue was associated
      with longer DFS with sunitinib but not placebo, suggesting predictive treatment
      effect utility. Further independent cohort validation studies are warranted. The
      prognostic value of PD-L1 expression in primary tumors from patients with high
      risk nonmetastatic RCC should also be further explored. Clin Cancer Res; 24(7);
      1554-61. (c)2018 AACR.

PMID- 29374055
TI  - Circulating Tumor Cells with Stem-Like Phenotypes for Diagnosis, Prognosis, and
      Therapeutic Response Evaluation in Hepatocellular Carcinoma.
AB  - Background: In the present study, we assessed the clinical value of circulating
      tumor cells (CTC) with stem-like phenotypes for diagnosis, prognosis, and
      surveillance in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) by
      an optimized qPCR-based detection platform.Methods: Differing subsets of CTCs
      were investigated, and a multimarker diagnostic CTC panel was constructed in a
      multicenter patient study with independent validation (total n = 1,006),
      including healthy individuals and patients with chronic hepatitis B infection
      (CHB), liver cirrhosis (LC), benign hepatic lesion (BHL), and HBV-related HCC,
      with area under the receiver operating characteristic curve (AUC-ROC) reflecting
      diagnostic accuracy. The role of the CTC panel in treatment response surveillance
      and its prognostic significance were further investigated.Results: The AUC of the
      CTC panel was 0.88 in the training set [sensitivity = 72.5%, specificity = 95.0%,
      positive predictive value (PPV) = 92.4, negative predictive value (NPV) = 77.8]
      and 0.93 in the validation set (sensitivity = 82.1%, specificity = 94.2%, PPV =
      89.9, NPV = 89.3). This panel performed equally well in detecting early-stage and
      alpha-fetoprotein-negative HCC, as well as differentiating HCC from CHB, LC, and
      BHL. The CTC load was decreased significantly after tumor resection, and patients
      with persistently high CTC load showed a propensity of tumor recurrence after
      surgery. The prognostic significance of the CTC panel in predicting tumor
      recurrence was further confirmed [training: HR = 2.692; 95% confidence interval
      (CI), 1.617-4.483; P < 0.001; and validation: HR = 3.127; 95% CI, 1.360-7.190; P
      = 0.007].Conclusions: Our CTC panel showed high sensitivity and specificity in
      HCC diagnosis and could be a real-time parameter for risk prediction and
      treatment monitoring, enabling early decision-making to tailor effective
      antitumor strategies. Clin Cancer Res; 24(9); 2203-13. (c)2018 AACR.

PMID- 29374056
TI  - A dual role of the extracellular domain of Drosophila Crumbs for morphogenesis of
      the embryonic neuroectoderm.
AB  - Epithelia are highly polarised tissues and several highly conserved polarity
      protein complexes serve to establish and maintain polarity. The transmembrane
      protein Crumbs (Crb), the central component of the Crb protein complex, is
      required, among others, for the maintenance of polarity in most epithelia in the
      Drosophila embryo. However, different epithelia exhibit different phenotypic
      severity upon loss of crb Using a transgenomic approach allowed us to more
      accurately define the role of crb in different epithelia. In particular, we
      provide evidence that the loss of epithelial tissue integrity in the ventral
      epidermis of crb mutant embryos is due to impaired actomyosin activity and an
      excess number of neuroblasts. We demonstrate that the intracellular domain of Crb
      could only partially rescue this phenotype, while it is able to completely
      restore tissue integrity in other epithelia. Based on these results we suggest a
      dual role of the extracellular domain of Crb in the ventral neuroectoderm. First,
      it is required for apical enrichment of the Crb protein, which in turn regulates
      actomyosin activity and thereby ensures tissue integrity; and second, the
      extracellular domain of Crb stabilises the Notch receptor and thereby ensures
      proper Notch signalling and specification of the correct number of neuroblasts.

PMID- 29374057
TI  - Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced
      degradation of HMG-CoA reductase.
AB  - Cholesterol biosynthesis is tightly regulated in the cell. For example, high
      sterol concentrations can stimulate degradation of the rate-limiting cholesterol
      biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA
      reductase, HMGCR). HMGCR is broken down by the endoplasmic reticulum membrane
      associated protein complexes consisting of insulin-induced genes (Insigs) and the
      E3 ubiquitin ligase gp78. Here we found that HMGCR degradation is partially
      blunted in Chinese hamster ovary (CHO) cells lacking gp78 (gp78-KO). To identify
      other ubiquitin ligase(s) that may function together with gp78 in triggering
      HMGCR degradation, we performed a small-scale short hairpin RNA-based screening
      targeting endoplasmic reticulum-localized E3s. We found that knockdown of both
      ring finger protein 145 (Rnf145) and gp78 genes abrogates sterol-induced
      degradation of HMGCR in CHO cells. We also observed that RNF145 interacts with
      Insig-1 and -2 proteins and ubiquitinates HMGCR. Moreover, the tetrapeptide
      sequence YLYF in the sterol-sensing domain and the Cys-537 residue in the RING
      finger domain were essential for RNF145 binding to Insigs and RNF145 E3 activity,
      respectively. Of note, amino acid substitutions in the YLYF or of Cys-537
      completely abolished RNF145-mediated HMGCR degradation. In summary, our study
      reveals that RNF145, along with gp78, promotes HMGCR degradation in response to
      elevated sterol levels and identifies residues essential for RNF145 function.

PMID- 29374058
TI  - Glioma tumor suppressor candidate region gene 1 (GLTSCR1) and its paralog GLTSCR1
      like form SWI/SNF chromatin remodeling subcomplexes.
AB  - The mammalian SWI/SNF chromatin remodeling complex is a heterogeneous collection
      of related protein complexes required for gene regulation and genome integrity.
      It contains a central ATPase (BRM or BRG1) and various combinations of 10-14
      accessory subunits (BAFs for BRM/BRG1 Associated Factors). Two distinct complexes
      differing in size, BAF and the slightly larger polybromo-BAF (PBAF), share many
      of the same core subunits but are differentiated primarily by having either AT
      rich interaction domain 1A/B (ARID1A/B in BAF) or ARID2 (in PBAF). Using density
      gradient centrifugation and immunoprecipitation, we have identified and
      characterized a third and smaller SWI/SNF subcomplex. We termed this complex GBAF
      because it incorporates two mutually exclusive paralogs, GLTSCR1 (glioma tumor
      suppressor candidate region gene 1) or GLTSCR1L (GLTSCR1-like), instead of an
      ARID protein. In addition to GLTSCR1 or GLTSCR1L, the GBAF complex contains BRD9
      (bromodomain-containing 9) and the BAF subunits BAF155, BAF60, SS18, BAF53a, and
      BRG1/BRM. We observed that GBAF does not contain the core BAF subunits BAF45,
      BAF47, or BAF57. Even without these subunits, GBAF displayed in vitro ATPase
      activity and bulk chromatin affinity comparable to those of BAF. GBAF associated
      with BRD4, but, unlike BRD4, the GBAF component GLTSCR1 was not required for the
      viability of the LNCaP prostate cancer cell line. In contrast, GLTSCR1 or
      GLTSCR1L knockouts in the metastatic prostate cancer cell line PC3 resulted in a
      loss in proliferation and colony-forming ability. Taken together, our results
      provide evidence for a compositionally novel SWI/SNF subcomplex with cell type
      specific functions.

PMID- 29374059
TI  - Thermodynamic characterization of the multivalent interactions underlying rapid
      and selective translocation through the nuclear pore complex.
AB  - Intrinsically disordered proteins (IDPs) play important roles in many biological
      systems. Given the vast conformational space that IDPs can explore, the
      thermodynamics of the interactions with their partners is closely linked to their
      biological functions. Intrinsically disordered regions of Phe-Gly nucleoporins
      (FG Nups) that contain multiple phenylalanine-glycine repeats are of particular
      interest, as their interactions with transport factors (TFs) underlie the
      paradoxically rapid yet also highly selective transport of macromolecules
      mediated by the nuclear pore complex. Here, we used NMR and isothermal titration
      calorimetry to thermodynamically characterize these multivalent interactions.
      These analyses revealed that a combination of low per-FG motif affinity and the
      enthalpy-entropy balance prevents high-avidity interaction between FG Nups and
      TFs, whereas the large number of FG motifs promotes frequent FG-TF contacts,
      resulting in enhanced selectivity. Our thermodynamic model underlines the
      importance of functional disorder of FG Nups. It helps explain the rapid and
      selective translocation of TFs through the nuclear pore complex and further
      expands our understanding of the mechanisms of "fuzzy" interactions involving
      IDPs.

PMID- 29374060
TI  - S-Glutathionylation of estrogen receptor alpha affects dendritic cell function.
AB  - Glutathione S-transferase Pi (GSTP) is a thiolase that catalyzes the addition of
      glutathione (GSH) to receptive cysteines in target proteins, producing an S
      glutathionylated residue. Accordingly, previous studies have reported that S
      glutathionylation is constitutively decreased in cells from mice lacking GSTP
      (Gstp1/p2-/-). Here, we found that bone marrow-derived dendritic cells (BMDDCs)
      from Gstp1/p2-/- mice have proliferation rates that are greater than those in
      their WT counterparts (Gstp1/p2+/+). Moreover, Gstp1/p2-/- BMDDCs had increased
      reactive oxygen species (ROS) levels and decreased GSH:glutathione disulfide
      (GSSG) ratios. Estrogen receptor alpha (ERalpha) is linked to myeloproliferation
      and differentiation, and we observed that its steady-state levels are elevated in
      Gstp1/p2-/- BMDDCs, indicating a link between GSTP and ERalpha activities. BMDDCs
      differentiated by granulocyte-macrophage colony-stimulating factor had elevated
      ERalpha levels, which were more pronounced in Gstp1/p2-/- than WT mice. When
      stimulated with lipopolysaccharide for maturation, Gstp1/p2-/- BMDDCs exhibited
      augmented endocytosis, maturation rate, cytokine secretion, and T-cell
      activation; heightened glucose uptake and glycolysis; increased Akt signaling (in
      the mTOR pathway); and decreased AMPK-mediated phosphorylation of proteins. Of
      note, GSTP formed a complex with ERalpha, stimulating ERalpha S-glutathionylation
      at cysteines 221, 245, 417, and 447; altering ERalpha's binding affinity for
      estradiol; and reducing overall binding potential (receptor density and affinity)
      3-fold. Moreover, in Gstp1/p2-/- BMDDCs, ERalpha S-glutathionylation was
      constitutively decreased. Taken together, these findings suggest that GSTP
      mediated S-glutathionylation of ERalpha controls BMDDC differentiation and
      affects metabolic function in dendritic cells.

PMID- 29374061
TI  - Leptin enhances hypothalamic lactate dehydrogenase A (LDHA)-dependent glucose
      sensing to lower glucose production in high-fat-fed rats.
AB  - The responsiveness of glucose sensing per se to regulate whole-body glucose
      homeostasis is dependent on the ability of a rise in glucose to lower hepatic
      glucose production and increase peripheral glucose uptake in vivo In both rodents
      and humans, glucose sensing is lost in diabetes and obesity, but the site(s) of
      impairment remains elusive. Here, we first report that short-term high-fat
      feeding disrupts hypothalamic glucose sensing to lower glucose production in
      rats. Second, leptin administration into the hypothalamus of high-fat-fed rats
      restored hypothalamic glucose sensing to lower glucose production during a
      pancreatic (basal insulin)-euglycemic clamp and increased whole-body glucose
      tolerance during an intravenous glucose tolerance test. Finally, both chemical
      inhibition of hypothalamic lactate dehydrogenase (LDH) (achieved via hypothalamic
      LDH inhibitor oxamate infusion) and molecular knockdown of LDHA (achieved via
      hypothalamic lentiviral LDHA shRNA injection) negated the ability of hypothalamic
      leptin infusion to enhance glucose sensing to lower glucose production in high
      fat-fed rats. In summary, our findings illustrate that leptin enhances LDHA
      dependent glucose sensing in the hypothalamus to lower glucose production in high
      fat-fed rodents in vivo.

PMID- 29374063
TI  - Putting Canoe in place: a tale of two GEFs.

PMID- 29374062
TI  - Protein binders and their applications in developmental biology.
AB  - Developmental biology research would benefit greatly from tools that enable
      protein function to be regulated, both systematically and in a precise spatial
      and temporal manner, in vivo In recent years, functionalized protein binders have
      emerged as versatile tools that can be used to target and manipulate proteins.
      Such protein binders can be based on various scaffolds, such as nanobodies,
      designed ankyrin repeat proteins (DARPins) and monobodies, and can be used to
      block or perturb protein function in living cells. In this Primer, we provide an
      overview of the protein binders that are currently available and highlight recent
      progress made in applying protein binder-based tools in developmental and
      synthetic biology.

PMID- 29374064
TI  - Forkhead Box F2 Suppresses Gastric Cancer through a Novel FOXF2-IRF2BPL-beta
      Catenin Signaling Axis.
AB  - DNA methylation has been identified as a hallmark of gastric cancer (GC).
      Identifying genes that are repressed by DNA promoter methylation is essential in
      providing insights into the molecular pathogenesis of gastric cancer. Using
      genome-wide methylation studies, we identified that transcription factor forkhead
      box F2 (FOXF2) was preferentially methylated in gastric cancer. We then
      investigated the functional significance and clinical implication of FOXF2 in
      gastric cancer. FOXF2 was silenced in gastric cancer cell lines and cancer
      tissues by promoter methylation, which was negatively associated with mRNA
      expression. Ectopic expression of FOXF2 inhibited proliferation, colony
      formation, G1-S cell-cycle transition, induced apoptosis of gastric cancer cell
      lines, and suppressed growth of xenograft tumors in nude mice; knockdown of FOXF2
      elicited opposing effects. FOXF2 inhibited Wnt signaling by inducing beta-catenin
      protein ubiquitination and degradation independently of GSK-3beta. FOXF2 directly
      bound the promoter of E3 ligase interferon regulatory factor 2-binding protein
      like (IRF2BPL) and induced its transcriptional expression. IRF2BPL in turn
      interacted with beta-catenin, increasing its ubiquitination and degradation.
      Multivariate Cox regression analysis identified FOXF2 hypermethylation as an
      independent prognostic factor of poor survival in early-stage gastric cancer
      patients. In conclusion, FOXF2 is a critical tumor suppressor in gastric
      carcinogenesis whose methylation status serves as an independent prognostic
      factor for gastric cancer patients.Significance: FOXF2-mediated upregulation of
      the E3 ligase IRF2BPL drives ubiquitylation and degradation of beta-catenin in
      gastric cancer, blunting Wnt signaling and suppressing carcinogenesis. Cancer
      Res; 78(7); 1643-56. (c)2018 AACR.

PMID- 29374066
TI  - miR-508 Defines the Stem-like/Mesenchymal Subtype in Colorectal Cancer.
AB  - Colorectal cancer includes an invasive stem-like/mesenchymal subtype, but its
      genetic drivers, functional, and clinical relevance are uncharacterized. Here we
      report the definition of an altered miRNA signature defining this subtype that
      includes a major genomic loss of miR-508. Mechanistic investigations showed that
      this miRNA affected the expression of cadherin CDH1 and the transcription factors
      ZEB1, SALL4, and BMI1. Loss of miR-508 in colorectal cancer was associated with
      upregulation of the novel hypoxia-induced long noncoding RNA AK000053. Ectopic
      expression of miR-508 in colorectal cancer cells blunted epithelial-to
      mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro
      and in vivo In clinical colorectal cancer specimens, expression of miR-508
      negatively correlated with stemness and EMT-associated gene expression and
      positively correlated with patient survival. Overall, our results showed that miR
      508 is a key functional determinant of the stem-like/mesenchymal colorectal
      cancer subtype and a candidate therapeutic target for its treatment.Significance:
      These results define a key functional determinant of a stem-like/mesenchymal
      subtype of colorectal cancers and a candidate therapeutic target for its
      treatment. Cancer Res; 78(7); 1751-65. (c)2018 AACR.

PMID- 29374067
TI  - RNF6 Promotes Colorectal Cancer by Activating the Wnt/beta-Catenin Pathway via
      Ubiquitination of TLE3.
AB  - Gene amplification is a hallmark of cancer and is frequently observed in
      colorectal cancer. Previous whole-genome sequencing of colorectal cancer clinical
      specimens identified amplification of Ring finger protein 6 (RNF6), a RING-domain
      E3 ubiquitin ligase. In this study, we showed that RNF6 is upregulated in 73.5%
      (147/200) of patients with colorectal cancer and was positively associated with
      RNF6 gene amplification. Furthermore, RNF6 expression and its gene amplification
      were independent prognostic factors for poor outcome of patients with colorectal
      cancer. RNF6 promoted cell growth, cell-cycle progression, and epithelial-to
      mesenchymal transition in colorectal cancer cells; RNF6 also promoted colorectal
      tumor growth and lung metastasis in mouse models. Mechanistic investigations
      revealed that RNF6 bound and ubiquitylated transducin-like enhancer of split 3
      (TLE3), a transcriptional repressor of the beta-catenin/TCF4 complex. RNF6
      mediated degradation of TLE3 significantly suppressed the association of TLE3
      with TCF4/LEF, which in turn led to recruitment of beta-catenin to TCF4/LEF,
      triggering Wnt/beta-catenin activation. Restoration of TLE3 expression abolished
      the oncogenic effects of RNF6. Taken together, these results demonstrate that
      RNF6 plays a pivotal oncogenic role in colorectal tumorigenesis.Significance:
      RNF6-mediated ubiquitination and degradation of TLE3 activates the Wnt/beta
      catenin pathway in colorectal carcinogenesis. Cancer Res; 78(8); 1958-71. (c)2018
      AACR.

PMID- 29374068
TI  - Successful Treatment of Scleredema Diabeticorum With Tranilast: Three Case
      Reports.

PMID- 29374065
TI  - Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor
      Cell Activity in Patients with Ovarian Cancer.
AB  - Metformin is a broadly prescribed drug for type 2 diabetes that exerts antitumor
      activity, yet the mechanisms underlying this activity remain unclear. We show
      here that metformin treatment blocks the suppressive function of myeloid-derived
      suppressor cells (MDSC) in patients with ovarian cancer by downregulating the
      expression and ectoenzymatic activity of CD39 and CD73 on monocytic and
      polymononuclear MDSC subsets. Metformin triggered activation of AMP-activated
      protein kinase alpha and subsequently suppressed hypoxia-inducible factor alpha,
      which was critical for induction of CD39/CD73 expression in MDSC. Furthermore,
      metformin treatment correlated with longer overall survival in diabetic patients
      with ovarian cancer, which was accompanied by a metformin-induced reduction in
      the frequency of circulating CD39+CD73+ MDSC and a concomitant increase in the
      antitumor activities of circulating CD8+ T cells. Our results highlight a direct
      effect of metformin on MDSC and suggest that metformin may yield clinical benefit
      through improvement of antitumor T-cell immunity by dampening CD39/CD73-dependent
      MDSC immunosuppression in ovarian cancer patients.Significance: The antitumor
      activity of an antidiabetes drug is attributable to reduced immunosuppressive
      activity of myeloid-derived tumor suppressor cells. Cancer Res; 78(7); 1779-91.
      (c)2018 AACR.

PMID- 29374069
TI  - Type 1 Diabetes in Parents and Risk of Attention Deficit/Hyperactivity Disorder
      in Offspring: A Population-Based Study in Sweden.
AB  - OBJECTIVE: To explore whether a family history of type 1 diabetes (T1D) is
      associated with an increased incidence of attention deficit/hyperactivity
      disorder (ADHD) in offspring. RESEARCH DESIGN AND METHODS: Individuals with T1D
      were identified from the nationwide Swedish National Hospital Discharge Register
      and Swedish Outpatient Register in Sweden and were linked to the Swedish Multi
      Generation Register to identify their offspring. Cox regression was used to
      calculate the hazard ratio (HR) of ADHD in offspring of patients with T1D
      compared with the general population. RESULTS: A total of 15,615 individuals were
      born after their parents were diagnosed with T1D. After a set of confounding
      factors was controlled for, offspring of T1D patients had a significantly
      increased risk of ADHD with an HR of 1.29 (95% CI 1.15-1.42). Maternal T1D was
      associated with an enhanced risk of ADHD (HR 1.35 [95% CI 1.18-1.55]) compared
      with paternal T1D (HR 1.20 [95% CI 1.03-1.41]), but the difference was not
      statistically significant. CONCLUSIONS: In this retrospective cohort study, we
      found that a parental history of T1D was associated with a 29% increased risk of
      being diagnosed with ADHD. However, the underlying mechanisms need to be explored
      in future studies.

PMID- 29374070
TI  - An ancient Sec10-formin fusion provides insights into actin-mediated regulation
      of exocytosis.
AB  - Exocytosis, facilitated by the exocyst, is fundamentally important for remodeling
      cell walls and membranes. Here, we analyzed For1F, a novel gene that encodes a
      fusion of an exocyst subunit (Sec10) and an actin nucleation factor (formin). We
      showed that the fusion occurred early in moss evolution and has been retained for
      more than 170 million years. In Physcomitrella patens, For1F is essential, and
      the expressed protein is a fusion of Sec10 and formin. Reduction of For1F or
      actin filaments inhibits exocytosis, and For1F dynamically associates with Sec6,
      another exocyst subunit, in an actin-dependent manner. Complementation
      experiments demonstrate that constitutive expression of either half of the gene
      or the paralogous Sec10b rescues loss of For1F, suggesting that fusion of the two
      domains is not essential, consistent with findings in yeast, where formin and the
      exocyst are linked noncovalently. Although not essential, the fusion may have had
      selective advantages and provides a unique opportunity to probe actin regulation
      of exocytosis.

PMID- 29374071
TI  - Effects of active acromegaly on bone mRNA and microRNA expression patterns.
AB  - OBJECTIVE: To evaluate the response of bone to chronic long-term growth hormone
      (GH) and insulin-like growth factor-1 (IGF1) excess by measuring the expression
      of selected mRNA and microRNA (miR) in bone tissue samples of patients with
      active acromegaly. DESIGN: Case-control study. METHODS: Bone tissue samples were
      obtained during transsphenoidal adenomectomy from the sphenoid bone (sella
      turcica) from 14 patients with clinically and biochemically confirmed acromegaly
      and 10 patients with clinically non-functioning pituitary adenoma (NFPA) matched
      by sex and age. Expression of genes involved in the regulation of bone remodeling
      was studied using quantitative polymerase chain reaction (qPCR). RESULTS: Of the
      genes involved in osteoblast and osteoclast activity, only alkaline phosphatase
      (ALP) mRNA was 50% downregulated in patients with acromegaly. GH excess caused
      increased expression of the Wnt signaling antagonists (DKK1) and agonists
      (WNT10B) and changes in the levels of miR involved in mesenchymal stem cell
      commitment to chondrocytes (miR-199a-5p) or adipocytes (miR-27-5p, miR-125b-5p,
      miR-34a-5p, miR-188-3p) P < 0.05; q < 0.1. Relevant compensatory mechanisms were
      found through the changes in miR involved in osteoblastogenesis (miR-210-5p, miR
      135a-5p, miR-211, miR-23a-3p, miR-204-5p), but the expression of TWIST1 was 50%
      downregulated and RUNX2 was unchanged. CONCLUSIONS: Acromegaly had minimal
      effects on tested mRNAs specific to osteoblast or osteoclast function except for
      downregulated ALP expression. The expressions of miR known to be involved in
      mesenchymal stem cell commitment and downregulated TWIST1 expression suggest
      acromegaly has a negative effect on osteoblastogenesis.

PMID- 29374072
TI  - Asb2alpha-Filamin A Axis Is Essential for Actin Cytoskeleton Remodeling During
      Heart Development.
AB  - RATIONALE: Heart development involves differentiation of cardiac progenitors and
      assembly of the contractile sarcomere apparatus of cardiomyocytes. However,
      little is known about the mechanisms that regulate actin cytoskeleton remodeling
      during cardiac cell differentiation. OBJECTIVE: The Asb2alpha (Ankyrin repeat
      containing protein with a suppressor of cytokine signaling box 2) CRL5 (cullin 5
      RING E3 ubiquitin ligase) triggers polyubiquitylation and subsequent degradation
      by the proteasome of FLNs (filamins). Here, we investigate the role of Asb2alpha
      in heart development and its mechanisms of action. METHODS AND RESULTS: Using
      Asb2 knockout embryos, we show that Asb2 is an essential gene, critical to heart
      morphogenesis and function, although its loss does not interfere with the overall
      patterning of the embryonic heart tube. We show that the Asb2alpha E3 ubiquitin
      ligase controls Flna stability in immature cardiomyocytes. Importantly, Asb2alpha
      mediated degradation of the actin-binding protein Flna marks a previously
      unrecognized intermediate step in cardiac cell differentiation characterized by
      cell shape changes and actin cytoskeleton remodeling. We further establish that
      in the absence of Asb2alpha, myofibrils are disorganized and that heartbeats are
      inefficient, leading to embryonic lethality in mice. CONCLUSIONS: These findings
      identify Asb2alpha as an unsuspected key regulator of cardiac cell
      differentiation and shed light on the molecular and cellular mechanisms
      determining the onset of myocardial cell architecture and its link with early
      cardiac function. Although Flna is known to play roles in cytoskeleton
      organization and to be required for heart function, this study now reveals that
      its degradation mediated by Asb2alpha ensures essential functions in
      differentiating cardiac progenitors.

PMID- 29374073
TI  - Genetic Fate Mapping Defines the Vascular Potential of Endocardial Cells in the
      Adult Heart.
AB  - RATIONALE: Endocardium is the major source of coronary endothelial cells (ECs) in
      the fetal and neonatal hearts. It remains unclear whether endocardium in the
      adult stage is also the main origin of neovascularization after cardiac injury.
      OBJECTIVE: To define the vascular potential of adult endocardium in homeostasis
      and after cardiac injuries by fate-mapping studies. METHODS AND RESULTS: We
      generate an inducible adult endocardial Cre line (Npr3 [natriuretic peptide
      receptor C]-CreER) and show that Npr3-CreER efficiently and specifically labels
      endocardial cells but not coronary blood vessels in the adult heart. The adult
      endocardial cells do not contribute to any vascular ECs during cardiac
      homeostasis. To examine the formation of blood vessels from endocardium after
      injury, we generate 4 cardiac injury models with Npr3-CreER mice: myocardial
      infarction, myocardial ischemia-reperfusion, cryoinjury, and transverse aortic
      constriction. Lineage tracing experiments show that adult endocardium minimally
      contributes to coronary ECs after myocardial infarction. In the myocardial
      ischemia-reperfusion, cryoinjury, or transverse aortic constriction models, adult
      endocardial cells do not give rise to any vascular ECs, and they remain on the
      inner surface of myocardium that connects with lumen circulation. In the
      myocardial infarction model, very few endocardial cells are trapped in the
      infarct zone of myocardium shortly after ligation of coronary artery, indicating
      the involvement of endocardial entrapment during blood vessels formation. When
      these adult endocardial cells are relocated and trapped in the infarcted
      myocardium by transplantation or myocardial constriction model, very few
      endocardial cells survive and gain vascular EC properties, and their contribution
      to neovascularization in the injured myocardium remains minimal. CONCLUSIONS:
      Unlike its fetal or neonatal counterpart, adult endocardium naturally generates
      minimal, if any, coronary arteries or vascular ECs during cardiac homeostasis or
      after injuries.

PMID- 29374074
TI  - CD22 Promotes B-1b Cell Responses to T Cell-Independent Type 2 Antigens.
AB  - CD22 (Siglec-2) is a critical regulator of B cell activation and survival. CD22-/
      mice generate significantly impaired Ab responses to T cell-independent type 2
      (TI-2) Ags, including haptenated Ficoll and pneumococcal polysaccharides, Ags
      that elicit poor T cell help and activate BCR signaling via multivalent epitope
      crosslinking. This has been proposed to be due to impaired marginal zone (MZ) B
      cell development/maintenance in CD22-/- mice. However, mice expressing a mutant
      form of CD22 unable to bind sialic acid ligands generated normal TI-2 Ab
      responses, despite significantly reduced MZ B cells. Moreover, mice treated with
      CD22 ligand-binding blocking mAbs, which deplete MZ B cells, had little effect on
      TI-2 Ab responses. We therefore investigated the effects of CD22 deficiency on B
      1b cells, an innate-like B cell population that plays a key role in TI-2 Ab
      responses. B-1b cells from CD22-/- mice had impaired BCR-induced proliferation
      and significantly increased intracellular Ca2+ concentration responses following
      BCR crosslinking. Ag-specific B-1b cell expansion and plasmablast differentiation
      following TI-2 Ag immunization was significantly impaired in CD22-/- mice,
      consistent with reduced TI-2 Ab responses. We generated CD22-/- mice with reduced
      CD19 levels (CD22-/-CD19+/-) to test the hypothesis that augmented B-1b cell BCR
      signaling in CD22-/- mice contributes to impaired TI-2 Ab responses. BCR-induced
      proliferation and intracellular Ca2+ concentration responses were normalized in
      CD22-/-CD19+/- B-1b cells. Consistent with this, TI-2 Ag-specific B-1b cell
      expansion, plasmablast differentiation, survival, and Ab responses were rescued
      in CD22-/-CD19+/- mice. Thus, CD22 plays a critical role in regulating TI-2 Ab
      responses through regulating B-1b cell signaling thresholds.

PMID- 29374075
TI  - Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV
      Evasion of T Cell Immunity.
AB  - Unlike cytosolic processing and presentation of viral Ags by virus-infected
      cells, Ags first expressed in infected nonprofessional APCs, such as CD4+ T cells
      in the case of HIV, are taken up by dendritic cells and cross-presented. This
      generally requires entry through the endocytic pathway, where endosomal proteases
      have first access for processing. Thus, understanding virus escape during cross
      presentation requires an understanding of resistance to endosomal proteases, such
      as cathepsin S (CatS). We have modified HIV-1MN gp120 by mutating a key CatS
      cleavage site (Thr322Thr323) in the V3 loop of the immunodominant epitope
      IGPGRAFYTT to IGPGRAFYVV to prevent digestion. We found this mutation to
      facilitate cross-presentation and provide evidence from MHC binding and X-ray
      crystallographic structural studies that this results from preservation of the
      epitope rather than an increased epitope affinity for the MHC class I molecule.
      In contrast, when the protein is expressed by a vaccinia virus in the cytosol,
      the wild-type protein is immunogenic without this mutation. These proof-of
      concept results show that a virus like HIV, infecting predominantly
      nonprofessional presenting cells, can escape T cell recognition by incorporating
      a CatS cleavage site that leads to destruction of an immunodominant epitope when
      the Ag undergoes endosomal cross-presentation.

PMID- 29374077
TI  - CD11b+ Dendritic Cell-Mediated Anti-Mycobacterium tuberculosis Th1 Activation Is
      Counterregulated by CD103+ Dendritic Cells via IL-10.
AB  - Mycobacterium tuberculosis, the pathogen causing pulmonary tuberculosis (TB) in
      humans, has evolved to delay Th1 immunity in the lung. Although conventional
      dendritic cells (cDCs) are known to be critical to the initiation of T cell
      immunity, the differential roles and molecular mechanisms of migratory CD11b+ and
      CD103+ cDC subsets in anti-M. tuberculosis Th1 activation remain unclear. Using a
      murine model of pulmonary M. tuberculosis infection, we found that slow arrival
      of M. tuberculosis-bearing migratory CD11b+ and CD103+ cDCs at the draining lymph
      nodes preceded the much-delayed Th1 immunity and protection in the lung. Contrary
      to their previously described general roles in Th polarization, CD11b+ cDCs, but
      not CD103+ cDCs, were critically required for Th1 activation in draining lymph
      nodes following M. tuberculosis infection. CD103+ cDCs counterregulated CD11b+
      cDC-mediated Th1 activation directly by producing the immune-suppressive cytokine
      IL-10. Thus, our study provides new mechanistic insights into differential Th
      immune regulation by migratory cDC subsets and helps to develop novel vaccines
      and therapies.

PMID- 29374078
TI  - Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in
      Th1 Cells.
AB  - IL-10 is a pleiotropic cytokine with multifaceted functions in establishing
      immune homeostasis. Although expressed by Th1 and Th2 cells, conventional Th1
      cells produce marginal levels of IL-10 compared with their Th2 counterparts. In
      this study, we investigated the epigenetic mechanisms of Il-10 gene expression in
      Th1 cells. Bioinformatics EMBOSS CpG plot analysis and bisulfite pyrosequencing
      revealed three CpG DNA methylation sites in the Il-10 gene locus. Progressive DNA
      methylation at all of the CpG regions of interest (ROIs) established a repressive
      program of Il-10 gene expression in Th1 cells. Interestingly, Th1 cells treated
      with IL-12 and IL-27 cytokines, thereby mimicking a chronic inflammatory
      condition in vivo, displayed a significant increase in IL-10 production that was
      accompanied by selective DNA demethylation at ROI 3 located in intron 3. IL-10
      producing T cells isolated from lymphocytic choriomeningitis virus-infected mice
      also showed enhanced DNA demethylation at ROI 3. Binding of STAT1 and STAT3 to
      demethylated ROI 3 enhanced IL-10 expression in an IL-12/IL-27-dependent manner.
      Accordingly, CD4+ T cells isolated from STAT1- or STAT3-knockout mice were
      significantly defective in IL-10 production. Our data suggest that, although
      stably maintained DNA methylation at the promoter may repress IL-10 expression in
      Th1 cells, locus-specific reversible DNA demethylation may serve as a threshold
      platform to control transient Il-10 gene expression.

PMID- 29374076
TI  - PAD4 Deficiency Leads to Decreased Organ Dysfunction and Improved Survival in a
      Dual Insult Model of Hemorrhagic Shock and Sepsis.
AB  - Indirect acute respiratory distress syndrome (iARDS) is caused by a nonpulmonary
      inflammatory process resulting from insults such as nonpulmonary sepsis.
      Neutrophils are thought to play a significant role in mediating ARDS, with the
      development of iARDS being characterized by dysregulation and recruitment of
      activated neutrophils into the lung. Recently, a novel mechanism of microbial
      killing by neutrophils was identified through the formation of neutrophil
      extracellular traps (NETs). NETs are composed of large webs of decondensed
      chromatin released from activated neutrophils into the extracellular space; they
      are regulated by the enzyme peptidylarginine deiminase 4 (PAD4) through mediation
      of chromatin decondensation via citrullination of target histones. Components of
      NETs have been implicated in ARDS. However, it is unknown whether there is any
      pathological significance of NET formation in ARDS caused indirectly by
      nonpulmonary insult. We subjected PAD4-/- mice and wild-type mice to a "two-hit"
      model of hypovolemic shock (fixed-pressure hemorrhage [Hem]) followed by septic
      cecal ligation and puncture (CLP) insult (Hem/CLP). Mice were hemorrhaged and
      resuscitated; 24 h after Hem, mice were then subjected to CLP. Overall, PAD4
      deletion led to an improved survival as compared with wild-type mice. PAD4-/-
      mice displayed a marked decrease in neutrophil influx into the lung, as well
      decreased presence of proinflammatory mediators. PAD4-/- mice were also able to
      maintain baseline kidney function after Hem/CLP. These data taken together
      suggest PAD4-mediated NET formation contributes to the mortality associated with
      shock/sepsis and may play a role in the pathobiology of end organ injury in
      response to combined hemorrhage plus sepsis.

PMID- 29374080
TI  - Injury Prevention: where to from here?

PMID- 29374079
TI  - TLR7 escapes X chromosome inactivation in immune cells.
AB  - Toll-like receptor 7 (TLR7) is critical to the induction of antiviral immunity,
      but TLR7 dosage is also a key pathogenic factor in systemic lupus erythematosus
      (SLE), an autoimmune disease with strong female bias. SLE prevalence is also
      elevated in individuals with Klinefelter syndrome, who carry one or more
      supernumerary X chromosomes, suggesting that the X chromosome complement
      contributes to SLE susceptibility. TLR7 is encoded by an X chromosome locus, and
      we examined here whether the TLR7 gene evades silencing by X chromosome
      inactivation in immune cells from women and Klinefelter syndrome males. Single
      cell analyses of TLR7 allelic expression demonstrated that substantial fractions
      of primary B lymphocytes, monocytes, and plasmacytoid dendritic cells not only in
      women but also in Klinefelter syndrome males express TLR7 on both X chromosomes.
      Biallelic B lymphocytes from women displayed greater TLR7 transcriptional
      expression than the monoallelic cells, correlated with higher TLR7 protein
      expression in female than in male leukocyte populations. Biallelic B cells were
      preferentially enriched during the TLR7-driven proliferation of CD27+ plasma
      cells. In addition, biallelic cells showed a greater than twofold increase over
      monoallelic cells in the propensity to immunoglobulin G class switch during the
      TLR7-driven, T cell-dependent differentiation of naive B lymphocytes into
      immunoglobulin-secreting cells. TLR7 escape from X inactivation endows the B cell
      compartment with added responsiveness to TLR7 ligands. This finding supports the
      hypothesis that enhanced TLR7 expression owing to biallelism contributes to the
      higher risk of developing SLE and other autoimmune disorders in women and in men
      with Klinefelter syndrome.

PMID- 29374081
TI  - Write to the editor.

PMID- 29374082
TI  - Retraction: Car safety seats for children: rear facing for best protection.

PMID- 29374083
TI  - A model for the conformational activation of the structurally quiescent
      metalloprotease ADAMTS13 by von Willebrand factor.

PMID- 29374084
TI  - Pleiotropic effects of O-glycosylation in colon cancer.
AB  - Changes in the O-glycosylation of proteins have long been associated with the
      development of cancer, but establishing causal relationships between altered
      glycosylation and cancer progression remains incomplete. In this study, the
      authors perform comparative analyses of the cellular phenotypes, transcriptional
      changes, and alterations in the glycoproteome in colon cancer cells that
      differentially express one glycosyltransferase. Their results provide a wealth of
      data on which future studies can be based.

PMID- 29374085
TI  - Comparing Three Data Mining Algorithms for Identifying the Associated Risk
      Factors of Type 2 Diabetes
AB  - Background: Increasing the prevalence of type 2 diabetes has given rise to a
      global health burden and a concern among health service providers and health
      administrators. The current study aimed at developing and comparing some
      statistical models to identify the risk factors associated with type 2 diabetes.
      In this light, artificial neural network (ANN), support vector machines (SVMs),
      and multiple logistic regression (MLR) models were applied, using demographic,
      anthropometric, and biochemical characteristics, on a sample of 9528 individuals
      from Mashhad City in Iran. Methods: This study has randomly selected 6654 (70%)
      cases for training and reserved the remaining 2874 (30%) cases for testing. The
      three methods were compared with the help of ROC curve. Results: The prevalence
      rate of type 2 diabetes was 14% in our population. The ANN model had 78.7%
      accuracy, 63.1% sensitivity, and 81.2% specificity. Also, the values of these
      three parameters were 76.8%, 64.5%, and 78.9%, for SVM and 77.7%, 60.1%, and
      80.5% for MLR. The area under the ROC curve was 0.71 for ANN, 0.73 for SVM, and
      0.70 for MLR. Conclusion: Our findings showed that ANN performs better than the
      two models (SVM and MLR) and can be used effectively to identify the associated
      risk factors of type 2 diabetes.

PMID- 29374086
TI  - The role of tight junction proteins in ovarian follicular development and ovarian
      cancer.
AB  - Tight junctions (TJ) are protein structures that control the transport of water,
      ions and macromolecules across cell layers. Functions of the transmembrane TJ
      protein, occluding (OCLN) and the cytoplasmic TJ proteins, tight junction protein
      1 (TJP1; also known as zona occludens protein-1), cingulin (CGN) and claudins
      (CLDN) are reviewed, and current evidence of their role in the ovarian function
      is reviewed. Abundance of OCLN, CLDNs and TJP1 mRNA changed during follicular
      growth. In vitro treatment with various growth factors known to affect ovarian
      folliculogenesis indicated that CGN, OCLN and TJP1 are hormonally regulated. The
      summarized studies indicate that expression of TJ proteins (i.e., OCLN, CLDN,
      TJP1 and CGN) changes with follicle size in a variety of vertebrate species but
      whether these changes in TJ proteins are increased or decreased depends on
      species and cell type. Evidence indicates that autocrine, paracrine and endocrine
      regulators, such as fibroblast growth factor-9, epidermal growth factor,
      androgens, tumor necrosis factor-alpha and glucocorticoids may modulate these TJ
      proteins. Additional evidence presented indicates that TJ proteins may be
      involved in ovarian cancer development in addition to normal follicular and
      luteal development. A model is proposed suggesting that hormonal downregulation
      of TJ proteins during ovarian follicular development could reduce barrier
      function (i.e., selective permeability of molecules between theca and granulosa
      cells) and allow for an increase in the volume of follicular fluid as well as
      allow additional serum factors into the follicle that may directly impact
      granulosa cell functions.

PMID- 29374087
TI  - Food restriction but not fish oil increases fertility in hens: role of RARRES2?
AB  - Overfed hens selected for their rapid growth become fatter and develop
      reproductive disorders. Herein, we aimed to demonstrate that food restriction
      leading to a weight reduction and/or a supplementation with fish oil may be
      effective in preventing reproductive disorders through the regulation of
      adipokine expression in broiler hens. This study included four groups of food
      restricted (Rt) or ad libitum hens (Ad, feeding at a rate 1.7 times greater than
      Rt hens) supplemented or unsupplemented with fish oil (1%). The Rt diet
      significantly increased plasma chemerin (RARRES2) levels during the laying
      period, delayed sexual maturity by one week and improved egg quality and
      fertility. These effects were associated with higher progesterone production in
      response to IGF1 (or LH) in cultured granulosa cells and in vivo egg yolk, as
      compared with Ad hens. Fish oil supplementation had similar effects to the Rt
      diet on progesterone (P < 0.05), but without any effect on fertility. Using RT
      PCR, we found that RARRES2 levels were lower in theca cells of Rt hens and NAMPT
      levels were increased by the fish oil supplementation. A significant positive
      correlation between RARRES2 expression in granulosa cells and the weight of F1
      preovulatory follicle was observed, as well as a negative correlation of plasma
      RARRES2 levels with hatchability. Thus, food restriction but not fish oil
      supplementation improved fertility, and this was associated with variations in
      RARRES2 plasma and ovarian expression in hens.

PMID- 29374088
TI  - Healthcare utilisation and costs of home mechanical ventilation.
AB  - BACKGROUND: Individuals using home mechanical ventilation (HMV) frequently choose
      to live at home for quality of life, despite financial burden. Previous studies
      of healthcare utilisation and costs do not consider public and private
      expenditures, including caregiver time. OBJECTIVES: To determine public and
      private healthcare utilisation and costs for HMV users living at home in two
      Canadian provinces, and examine factors associated with higher costs. METHODS:
      Longitudinal, prospective observational cost analysis study (April 2012 to August
      2015) collecting data on public and private (out-of-pocket, third-party
      insurance, caregiving) costs every 2 weeks for 6 months using the Ambulatory and
      Home Care Record. Functional Independence Measure (FIM) was used at baseline and
      study completion. Regression models examined variables associated with total
      monthly costs selected a priori using Andersen and Newman's framework for
      healthcare utilisation, relevant literature, and clinical expertise. Data are
      reported in 2015 Canadian dollars ($C1=US$0.78=?0.51=?0.71). RESULTS: We enrolled
      134 HMV users; 95 with family caregivers. Overall median (IQR) monthly healthcare
      cost was $5275 ($2291-$10 181) with $2410 (58%) publicly funded; $1609 (39%)
      family caregiving; and $141 (3%) out-of-pocket (<1% third-party insurance).
      Median healthcare costs were $8733 ($5868-$15 274) for those invasively
      ventilated and $3925 ($1212-$7390) for non-invasive ventilation. Variables
      associated with highest monthly costs were amyotrophic lateral sclerosis (1.88,
      95% CI 1.09 to 3.26, P<0.03) and lower FIM quintiles (higher dependency) (up to
      6.98, 95% CI 3.88 to 12.55, P<0.0001) adjusting for age, sex, tracheostomy and
      ventilation duration. CONCLUSIONS: For HMV users, most healthcare costs were
      publicly supported or associated with family caregiving. Highest costs were
      incurred by the most dependent users. Understanding healthcare costs for HMV
      users will inform policy decisions to optimise resource allocation, helping
      individuals live at home while minimising caregiver burden.

PMID- 29374089
TI  - Pulmonary melioidosis with laryngeal involvement: an unusual site of infection.

PMID- 29374090
TI  - A runny nose.

PMID- 29374091
TI  - Recent advances in the understanding of endothelial barrier function and fluid
      therapy.
AB  - Elucidation of the structural basis of endothelial barrier function and the study
      of transcapillary fluid exchange dynamics are areas of active research. There has
      been significant enhancement in our understanding of the ultrastructural basis of
      endothelial barrier function. The role of glycocalyx has received special
      attention. Experimental evidence has called for a revision in the classic
      Starling principle of transcapillary exchange. The glycocalyx model provides a
      potential structural mechanism for the revised Starling principle. This knowledge
      can provide the framework for understanding the volume expansion effect of fluid
      therapy and the physiological basis of fluid therapy.

PMID- 29374093
TI  - Public smoking ban and socioeconomic inequalities in smoking prevalence and
      cessation: a cross-sectional population-based study in Geneva, Switzerland (1995
      2014).
AB  - INTRODUCTION: Smoking bans were suggested to reduce smoking prevalence and
      increase quit ratio but their equity impact remains unclear. We aimed to
      characterise the socioeconomic status (SES)-related inequalities in smoking
      prevalence and quit ratio before and after the implementation of a public smoking
      ban. METHODS: We included data from 17 544 participants in the population-based
      cross-sectional Bus Sante study in Geneva, Switzerland, between 1995 and 2014. We
      considered educational attainment (primary, secondary and tertiary) as a SES
      indicator. Outcomes were smoking prevalence (proportion of current smokers) and
      quit ratio (ex-smokers to ever-smokers ratio). We used segmented linear
      regression to assess the overall impact of smoking ban on outcome trends. We
      calculated the relative (RII) and slope (SII, absolute difference) indexes of
      inequality, quantifying disparities between educational groups in outcomes
      overall (1995-2014), before and after ban implementation (November 2009).
      RESULTS: Least educated participants displayed higher smoking prevalence
      (RII=2.04, P<0.001; SII=0.15, P<0.001) and lower quit ratio (RII=0.73, P<0.001;
      SII=-0.18, P<0.001). As in other studies, smoking ban implementation coincided
      with a temporary reduction of smoking prevalence (P=0.003) and increase in quit
      ratio (P=0.02), with a progressive return to preban levels. Inequalities
      increased (P<0.05) in relative terms for smoking prevalence (RIIbefore=1.84,
      P<0.001 and RIIafter=3.01, P<0.001) and absolute terms for both outcomes (smoking
      prevalence: SIIbefore=0.14, P<0.001 and SIIafter=0.19, P<0.001; quit ratio:
      SIIbefore=-0.15, P<0.001 and SIIafter=-0.27, P<0.001). CONCLUSIONS:
      Implementation of a public smoking ban coincided with a short-lived decrease in
      smoking prevalence and increase in quit ratio but also with a widening in SES
      inequalities in smoking-related outcomes.

PMID- 29374094
TI  - Heat-not-burn tobacco products: concerns from the Italian experience.

PMID- 29374092
TI  - MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated
      phenotype by deregulation of estrogen and NGF signaling.
AB  - Neuroblastoma (NB) is a remarkably heterogenic childhood tumor of the sympathetic
      nervous system with clinical behavior ranging from spontaneous regression to
      poorly differentiated tumors and metastasis. MYCN is amplified in 20% of cases
      and correlates with an undifferentiated, aggressive phenotype and poor prognosis.
      Estrogen receptor alpha (ERalpha) and the nerve growth factor (NGF) receptors
      TrkA and p75NTR are involved in neuronal differentiation and survival. We have
      previously shown that MYCN, via miR-18a, targets ERalpha in NB cells. Here, we
      demonstrate that interference with miR-18a or overexpression of ERalpha is
      sufficient to induce NGF signaling and to modulate both basal and NGF-induced
      neuronal differentiation in MYCN-amplified NB cells. Proteomic analysis confirmed
      an increase of neuronal features and showed that processes linked to tumor
      initiation and progression were inhibited upon ERalpha overexpression. Indeed,
      ectopic ERalpha expression was sufficient to inhibit metabolic activity and
      tumorigenic processes, including glycolysis, oxidative phosphorylation, cell
      viability, migration, and anchorage independent growth. Importantly, ERalpha
      overexpression reduced tumor burden in NB mouse models and high ERalpha levels
      were linked to improved survival in patients. In addition to ERalpha, several
      other nuclear hormone receptors (NHRs), including the glucocorticoid and the
      retinoic acid receptors, correlated with clinical markers for favorable and low
      stage NB disease. Our data suggest that MYCN targets ERalpha and thereby NGF
      signaling to maintain an undifferentiated and aggressive phenotype. Notably, we
      identified the estrogen-NGF crosstalk, as well as a set of other NHRs, as
      potential prognostic markers and targets for therapeutic strategies against NB.

PMID- 29374095
TI  - Bladder cancer and occupational exposure to metalworking fluid mist: a counter
      matched case-control study in French steel-producing factories.
AB  - OBJECTIVES: To assess the relationship between occupational exposure to
      metalworking fluids (MWFs) in the steel-producing industry and bladder cancer
      incidence. METHODS: A nested case-control study on bladder cancer was set up in a
      cohort of workers from six French steel-producing factories. Three controls were
      randomly selected for each incident bladder cancer case diagnosed from 2006 to
      2012. Controls were matched to cases on age at diagnosis and counter-matched on a
      surrogate measure of exposure to MWFs derived from a job-exposure matrix. Cases
      (n=84) and controls (n=251) were face-to-face interviewed. Experts assessed
      occupational exposure to MWFs (straight, soluble and synthetic) using
      questionnaires and reports from factory visits. Occupational exposures were based
      on three metrics: duration, frequency-weighted duration and cumulative exposure
      index. Conditional multiple logistic regressions were used to determine ORs and
      95% CIs, taking non-occupational and occupational exposure into account. RESULTS:
      In the 25 years before diagnosis, ORs increased significantly with duration of
      exposure to straight MWFs (OR=1.13 (1.02-1.25)) and increased with frequency
      weighted duration of exposure to straight MWFs (OR=1.44 (0.97-2.14)). These
      results remained valid after adjusting for duration of smoking, average number of
      cigarettes smoked per day, time since smoking cessation and exposure to
      polycyclic aromatic hydrocarbons (PAHs). ORs also increased with soluble MWFs but
      not significantly. No significant association was found with older exposures to
      MWFs or with exposure to synthetic MWFs. CONCLUSION: The increased risk of
      bladder cancer observed among workers exposed to straight MWFs and to a lesser
      extent to soluble MWFs may be explained by the presence of carcinogens (such as
      PAH) in mineral oils component of straight and soluble oils. Prevention therefore
      remains necessary in sectors using MWFs.

PMID- 29374096
TI  - Human service work, gender and antidepressant use: a nationwide register-based 19
      year follow-up of 752 683 women and men.
AB  - OBJECTIVES: To examine antidepressant use among male and female human service
      professionals. METHODS: A random sample of individuals between 25 years and 54
      years of age (n=752 683; 49.2% women; mean age 39.5 years). Information about
      each individual's filled antidepressant prescriptions from 1995 to 2014 was
      provided by the Social Insurance Institution. First, antidepressant use in five
      broad human service categories was compared with that in all other occupations
      grouped together, separately for men and women. Then, each of the 15 human
      service professions were compared with all other occupations from the same
      skill/education level (excluding other human services professions). Cox models
      were applied and the results are presented as HRs for antidepressant use with 95%
      CIs. RESULTS: The hazard of antidepressant use was higher among men working in
      human service versus all other occupations with the same skill/occupational level
      (1.22, 95% CI 1.18 to 1.27), but this was not the case for women (0.99, 95% CI
      0.98 to 1.01). The risks differed between professions: male health and social
      care professionals (including medical doctors, nurses, practical nurses and home
      care assistants), social workers, childcare workers, teachers and psychologists
      had a higher risk of antidepressant use than men in non-human service
      occupations, whereas customer clerks had a lower risk. CONCLUSIONS: Male human
      service professionals had a higher risk of antidepressant use than men working in
      non-human service occupations. Gendered sociocultural norms and values related to
      specific occupations as well as occupational selection may be the cause of the
      elevated risk.

PMID- 29374097
TI  - Incidence of cardiovascular disease in a historical cohort of Danish
      firefighters.
AB  - OBJECTIVES: Firefighters are exposed to multiple cardiovascular hazards, but few
      epidemiological studies have addressed their cardiovascular morbidity. The
      objective of this study was therefore to examine the incidence of cardiovascular
      diseases (CVD) in Danish firefighters. METHODS: We used individual historical
      employment records on 11.691 male Danish firefighters supplied by trade unions
      and fire agencies. The Supplementary Pension Fund Register was used to establish
      two occupational reference groups (a random sample from the male employed
      population and military employees). Information on CVD incidence was retrieved
      from the nationwide Danish National Patient Registry. SIRs and Poisson regression
      analyses (incidence rate ratio) were used for estimation of risks, including 95%
      CIs. RESULTS: In comparison with the population sample, the age-adjusted and
      calendar time-adjusted SIR for all CVDs combined was increased in firefighters
      (SIR=1.10, 95% CI 1.05 to 1.15). The risk was also elevated for the most frequent
      outcomes, including angina pectoris (SIR=1.16, 95% CI 1.08 to 1.24), acute
      myocardial infarction (SIR=1.16, 95% CI 1.06 to 1.26), chronic ischaemic heart
      disease (SIR=1.15, 95% CI 1.06 to 1.24) and atrial fibrillation/flutter
      (SIR=1.25, 95% CI 1.14 to 1.36). This analysis showed the most elevated SIRs for
      CVD in full-time firefighters compared with part-time/volunteer firefighters.
      Both types of firefighters employed <15 years had an increased risk of CVD.
      Similar risk patterns appeared in comparisons with the military. Internal
      analysis supported external findings. CONCLUSION: The risk of overall CVD,
      including the most frequent subtypes was modestly increased in Danish
      firefighters and was most elevated in full-time firefighters compared with other
      male employees.

PMID- 29374098
TI  - Social rank affects the haematologic profile in red deer hinds.
AB  - We studied the effects of social rank on the haematologic profile in a herd of 24
      female Iberian red deer hinds. Social rank hierarchy was determined and blood
      samples were taken and analysed. After adjusting for age and body mass, dominance
      ranking showed a significant negative effect (ie, lower values in dominant hinds)
      on white blood cell (WBC) count, haemoglobin and haematocrit. Our results are
      similar to those reported for stressed individuals due to physical
      immobilisation, but do not support the predicted enhanced erythropoiesis due to
      higher levels of androgens. The results for WBC numbers may also reflect that
      subordinate hinds must allocate a higher amount of resources to immunity as a
      result of injuries incurred from dominant hinds, while simultaneously facing
      restricted access to food sources. For red blood cell (RBC) counts, the results
      may be due to subordinate hinds likely needing increased haematocrit and
      haemoglobin levels for fast flight responses. Our data show that social rank
      influences haematologic profile, and thus it should be considered when correctly
      interpreting blood analyses in social cervid species.

PMID- 29374099
TI  - Comparative effectiveness of individualised homeopathy and antibiotics in the
      treatment of bovine clinical mastitis: randomised controlled trial.
AB  - : Based on the widespread use of homeopathy in dairy farm practice when treating
      mastitis, a blind randomised controlled trial (RCT) was conducted to assess the
      effectiveness of homeopathic treatment of clinical mastitis on four dairy farms.
      The study considered specific guidelines for RCTs as well as the basic principles
      of individualised homeopathy and involved 180 lactating dairy cows. Evaluation of
      cure rates was based on clinical investigation of the udder and on laboratory
      analysis of milk samples. In culture-positive cases, the antibiotic treatment
      provided suboptimal bacteriological cures (60-81 per cent) but was more effective
      than individualised homeopathy (33-43 per cent) whose effects appeared little
      different to those of placebos (45-47 per cent) (P<=0.05). On the cytological
      cure level, all three treatment methods were similarly ineffective: antibiotic
      being 2-21 per cent, individualised homeopathy 0-8 per cent and placebo 3-13 per
      cent (P<=0.05; P=0.13). Antibiotics, individualised homeopathy and placebo had
      similar effects on bacteriological and cytological cure in cases of culture
      negative milk samples (P>0.4) and Escherichia coli infections (P=1.0). The study
      results implied that the effectiveness of individualised homeopathy does not go
      beyond a placebo effect and successful treatment is highly dependent on the
      specific mastitis pathogen. Thus, antimicrobial or alternative remedies used
      should be based on the bacterial culture of the milk sample. TRIAL REGISTRATION
      NUMBER: NTP-ID: 00008011-1-9, Pre-results.

PMID- 29374100
TI  - Long-term complications following tibial plateau levelling osteotomy in small
      dogs with tibial plateau angles > 30 degrees .
AB  - Tibial plateau levelling osteotomy (TPLO) is commonly performed for surgical
      management of cranial cruciate ligament (CCL) disease. It has been suggested that
      small dogs may have steeper tibial plateau angles (TPAs) than large dogs, which
      has been associated with increased complication rates after TPLO. A retrospective
      study was performed to assess the rate and nature of long-term complications
      following TPLO in small dogs with TPAs>30 degrees . Medical records were reviewed
      for dogs with TPAs>30 degrees  treated for CCL rupture by TPLO with a 2.0 mm
      plate over a five-year period. Radiographs were assessed to determine TPA,
      postoperative tibial tuberosity width and to identify any complication. Up-to
      date medical records were obtained from the referring veterinary surgeon and any
      complications in the year after surgery were recorded. The effects of different
      variables on complication rate were assessed using logistic regression analysis.
      Minor complications were reported in 22.7 per cent of cases. This is similar to
      or lower than previously reported complication rates for osteotomy techniques in
      small dogs and dogs with steep TPAs. A smaller postoperative TPA was the only
      variable significantly associated with an increased complication rate. No major
      complications were identified.

PMID- 29374101
TI  - The effect of white matter hyperintensities on verbal memory: Mediation by
      temporal lobe atrophy.
AB  - OBJECTIVE: To determine the relationship between white matter hyperintensities
      (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe
      atrophy, and verbal memory deficits in Alzheimer disease (AD) and other
      dementias. METHODS: We recruited groups of participants with and without AD,
      including strata with extensive WMH and minimal WMH, into a cross-sectional proof
      of-principle study (n = 118). A consecutive case series from a memory clinic was
      used as an independent validation sample (n = 702; Sunnybrook Dementia Study;
      NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as
      the brain parenchymal fraction) using structural MRI and verbal memory using the
      California Verbal Learning Test. Using path modeling with an inferential
      bootstrapping procedure, we tested an indirect effect of WMH on verbal recall
      that depends sequentially on temporal lobe atrophy and verbal learning. RESULTS:
      In both samples, WMH predicted poorer verbal recall, specifically due to temporal
      lobe atrophy and poorer verbal learning (proof-of-principle -1.53, 95% bootstrap
      confidence interval [CI] -2.45 to -0.88; and confirmation -0.66, 95% CI [-0.95 to
      -0.41] words). This pathway was significant in subgroups with (-0.20, 95% CI [
      0.38 to -0.07] words, n = 363) and without (-0.71, 95% CI [-1.12 to -0.37] words,
      n = 339) AD. Via the identical pathway, WMH contributed to deficits in
      recognition memory (-1.82%, 95% CI [-2.64% to -1.11%]), a sensitive and specific
      sign of AD. CONCLUSIONS: Across dementia syndromes, WMH contribute indirectly to
      verbal memory deficits considered pathognomonic of Alzheimer disease,
      specifically by contributing to temporal lobe atrophy.

PMID- 29374102
TI  - Early time course of major bleeding on antiplatelet therapy after TIA or ischemic
      stroke.
AB  - OBJECTIVE: To study the early time course of major bleeding and its subtypes in
      patients with cerebral ischemia on dual and single antiplatelet therapy. METHODS:
      We performed a post hoc analysis on individual patient data from 6 randomized
      clinical trials (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic
      Events [CAPRIE], Second European Stroke Prevention Study [ESPS-2], Management of
      Atherothrombosis With Clopidogrel in High-Risk Patients [MATCH], Clopidogrel for
      High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance
      [CHARISMA], European/Australasian Stroke Prevention in Reversible Ischaemia Trial
      [ESPRIT], and Prevention Regimen for Effectively Avoiding Second Strokes
      [PRoFESS]) including 45,195 patients with a TIA or noncardioembolic ischemic
      stroke. We studied incidence rates of bleeding per antiplatelet regimen
      stratified by time from randomization (<=30, 31-90, 91-180, 181-365, >365 days).
      We calculated incidence rates per trial and pooled estimates with random-effects
      meta-analysis. We performed Poisson regression to assess differences between time
      periods with adjustment for age and sex. RESULTS: The incidence of major bleeding
      on aspirin plus clopidogrel and aspirin plus -dipyridamole was highest in the
      first 30 days, 5.8 and 4.9 per 100 person-years, respectively, and was
      significantly higher than at 31 to 90 days (rate ratio 1.98, 95% confidence
      interval 1.16-3.40 for aspirin plus clopidogrel; rate ratio 1.94, 95% confidence
      interval 1.24-3.03 for aspirin plus dipyridamole). Incidence rates on aspirin and
      clopidogrel monotherapy were 2.8 and 2.5 per 100 person-years, respectively, in
      the first 30 days, with no significant change over time. The time course was
      similar for gastrointestinal bleeds. There was no early excess of intracranial
      hemorrhage in patients on either dual or single antiplatelet therapy. CONCLUSION:
      Dual antiplatelet therapy is associated with high early risks of major and
      gastrointestinal bleeding that decline after the first month in trial cohorts.

PMID- 29374103
TI  - Erythrocyte Fraction Within Retrieved Thrombi Contributes to Thrombolytic
      Response in Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Recent advent of endovascular thrombectomy (EVT) enables
      us to provide a new perspective on the use of tPA (tissue-type plasminogen
      activator) through histological analysis of retrieved thrombus. We investigated
      the responsiveness of intravenous thrombolysis (IVT) according to the thrombus
      composition in EVT-attempted patients with acute ischemic stroke. METHODS: We
      reviewed 92 consecutive patients with anterior circulation stroke who received
      combined IVT and EVT for 2 years. IVT responsiveness is defined as any decrease
      in the clot burden from baseline computed tomographic angiography to digital
      subtraction angiography during EVT. We histologically analyzed the relative
      fractions of red blood cells (RBCs), congregated fibrin and platelets, and white
      blood cells in the retrieved thrombi using semiautomated color-based segmentation
      method. Clinical characteristics according to the RBC fraction were investigated,
      and associated factors with IVT responsiveness were explored. RESULTS: Fifty-two
      patients with histological analyses were stratified into lowest, middle, and
      highest tertiles of RBC fraction. Toward higher RBC fraction, there was more
      common susceptibility vessel signs on magnetic resonance imaging (50.0% versus
      66.7% versus 91.7%; P=0.022) and prevalent IVT responsiveness (25.0% versus 41.7%
      versus 75.0%; P=0.010). IVT-responsive group (n=23) had higher RBC fraction
      (45.7+/-15.5% versus 35.9+/-12.2%; P=0.010), lower fibrin and platelet (50.4+/
      14.0% versus 58.5+/-11.1%; P=0.027), and lower white blood cells fraction (3.9+/
      2.1% versus 5.5+/-3.0%; P=0.027) than IVT-unresponsive group (n=29). After
      adjusting for potential variables, RBC fraction (odds ratio, 1.05; 95% confidence
      interval, 1.01-1.10) remained only independent determinant of IVT responsiveness.
      CONCLUSIONS: In EVT-attempted patients with acute ischemic stroke, IVT
      responsiveness would be closely associated with RBC fraction.

PMID- 29374104
TI  - Functional Trajectories, Cognition, and Subclinical Cerebrovascular Disease.
AB  - BACKGROUND AND PURPOSE: Cognition and education influence functional
      trajectories, but whether associations differ with subclinical brain infarcts
      (SBI) or white matter hyperintensity volume (WMHV) is unknown. We hypothesized
      that SBI and WMHV moderated relationships between cognitive performance and
      education and functional trajectories. METHODS: A total of 1290 stroke-free
      individuals underwent brain magnetic resonance imaging and were followed for 7.3
      years (mean) with annual functional assessments with the Barthel index (range, 0
      100). Magnetic resonance imaging measurements included pathology-informed SBI (PI
      SBI) and WMHV (% total cranial volume). Generalized estimating equation models
      tested associations between magnetic resonance imaging variables and baseline
      Barthel index and change in Barthel index, adjusting for demographic, vascular,
      cognitive, and social risk factors, and stroke and myocardial infarction during
      follow-up. We tested interactions among education level, baseline cognitive
      performance (Mini-Mental State score), and functional trajectories and ran models
      stratified by levels of magnetic resonance imaging variables. RESULTS: Mean age
      was 70.6 (SD, 9.0) years; 19% had PI-SBI, and mean WMHV was 0.68%. Education did
      not modify associations between cognition and functional trajectories. PI-SBI
      modified associations between cognition and functional trajectories (P=0.04) with
      a significant protective effect of better cognition on functional decline seen
      only in those without PI-SBI. There was no significant interaction for WMHV
      (P=0.8). PI-SBI, and greater WMHV, were associated with 2- to 3-fold steeper
      functional decline, holding cognition constant. CONCLUSIONS: PI-SBI moderated the
      association between cognition and functional trajectories, with 3-fold greater
      decline among those with PI-SBI (compared with no PI-SBI) and normal baseline
      cognition. This highlights the strong and independent association between
      subclinical markers and patient-centered trajectories over time.

PMID- 29374105
TI  - Validating the TeleStroke Mimic Score: A Prediction Rule for Identifying Stroke
      Mimics Evaluated Over Telestroke Networks.
AB  - BACKGROUND AND PURPOSE: Up to 30% of acute stroke evaluations are deemed stroke
      mimics, and these are common in telestroke as well. We recently published a risk
      prediction score for use during telestroke encounters to differentiate stroke
      mimics from ischemic cerebrovascular disease derived and validated in the
      Partners TeleStroke Network. Using data from 3 distinct US and European
      telestroke networks, we sought to externally validate the TeleStroke Mimic (TM)
      score in a broader population. METHODS: We evaluated the TM score in 1930
      telestroke consults from the University of Utah, Georgia Regents University, and
      the German TeleMedical Project for Integrative Stroke Care Network. We report the
      area under the curve in receiver-operating characteristic curve analysis with 95%
      confidence interval for our previously derived TM score in which lower TM scores
      correspond with a higher likelihood of being a stroke mimic. RESULTS: Based on
      final diagnosis at the end of the telestroke consultation, there were 630 of 1930
      (32.6%) stroke mimics in the external validation cohort. All 6 variables included
      in the score were significantly different between patients with ischemic
      cerebrovascular disease versus stroke mimics. The TM score performed well (area
      under curve, 0.72; 95% confidence interval, 0.70-0.73; P<0.001), similar to our
      prior external validation in the Partners National Telestroke Network.
      CONCLUSIONS: The TM score's ability to predict the presence of a stroke mimic
      during telestroke consultation in these diverse cohorts was similar to its
      performance in our original cohort. Predictive decision-support tools like the TM
      score may help highlight key clinical differences between mimics and patients
      with stroke during complex, time-critical telestroke evaluations.

PMID- 29374106
TI  - Comorbid Psychiatric Disease Is Associated With Lower Rates of Thrombolysis in
      Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) improves outcomes after
      acute ischemic stroke but is underused in certain patient populations. Mental
      illness is pervasive in the United States, and patients with comorbid psychiatric
      disease experience inequities in treatment for a range of conditions. We aimed to
      determine whether comorbid psychiatric disease is associated with differences in
      IVT use in acute ischemic stroke. METHODS: Acute ischemic stroke admissions
      between 2007 and 2011 were identified in the Nationwide Inpatient Sample.
      Psychiatric disease was defined by International Classification of Diseases,
      Ninth Revision, Clinical Modification codes for secondary diagnoses of
      schizophrenia or other psychoses, bipolar disorder, depression, or anxiety. Using
      logistic regression, we tested the association between IVT and psychiatric
      disease, controlling for demographic, clinical, and hospital factors. RESULTS: Of
      the 325 009 ischemic stroke cases meeting inclusion criteria, 12.8% had any of
      the specified psychiatric comorbidities. IVT was used in 3.6% of those with, and
      4.4% of those without, psychiatric disease (P<0.001). Presence of any psychiatric
      disease was associated with lower odds of receiving IVT (adjusted odds ratio,
      0.80; 95% confidence interval, 0.76-0.85). When psychiatric diagnoses were
      analyzed separately individuals with schizophrenia or other psychoses, anxiety,
      or depression each had significantly lower odds of IVT compared to individuals
      without psychiatric disease. CONCLUSIONS: Acute ischemic stroke patients with
      comorbid psychiatric disease have significantly lower odds of IVT. Understanding
      barriers to IVT use in such patients may help in developing interventions to
      increase access to evidence-based stroke care.

PMID- 29374107
TI  - Potato Mop-Top Virus Co-Opts the Stress Sensor HIPP26 for Long-Distance Movement.
AB  - Virus movement proteins facilitate virus entry into the vascular system to
      initiate systemic infection. The potato mop-top virus (PMTV) movement protein,
      TGB1, is involved in long-distance movement of both viral ribonucleoprotein
      complexes and virions. Here, our analysis of TGB1 interactions with host
      Nicotiana benthamiana proteins revealed an interaction with a member of the heavy
      metal-associated isoprenylated plant protein family, HIPP26, which acts as a
      plasma membrane-to-nucleus signal during abiotic stress. We found that knockdown
      of NbHIPP26 expression inhibited virus long-distance movement but did not affect
      cell-to-cell movement. Drought and PMTV infection up-regulated NbHIPP26 gene
      expression, and PMTV infection protected plants from drought. In addition,
      NbHIPP26 promoter-reporter fusions revealed vascular tissue-specific expression.
      Mutational and biochemical analyses indicated that NbHIPP26 subcellular
      localization at the plasma membrane and plasmodesmata was mediated by lipidation
      (S-acylation and prenylation), as nonlipidated NbHIPP26 was predominantly in the
      nucleus. Notably, coexpression of NbHIPP26 with TGB1 resulted in a similar
      nuclear accumulation of NbHIPP26. TGB1 interacted with the carboxyl-terminal CVVM
      (prenyl) domain of NbHIPP26, and bimolecular fluorescence complementation
      revealed that the TGB1-HIPP26 complex localized to microtubules and accumulated
      in the nucleolus, with little signal at the plasma membrane or plasmodesmata.
      These data support a mechanism where interaction with TGB1 negates or reverses
      NbHIPP26 lipidation, thus releasing membrane-associated NbHIPP26 and redirecting
      it via microtubules to the nucleus, thereby activating the drought stress
      response and facilitating virus long-distance movement.

PMID- 29374108
TI  - Fine-Tuning of Photosynthesis Requires CURVATURE THYLAKOID1-Mediated Thylakoid
      Plasticity.
AB  - The thylakoid membrane system of higher plant chloroplasts consists of
      interconnected subdomains of appressed and nonappressed membrane bilayers, known
      as grana and stroma lamellae, respectively. CURVATURE THYLAKOID1 (CURT1) protein
      complexes mediate the shape of grana stacks in a dosage-dependent manner and
      facilitate membrane curvature at the grana margins, the interface between grana
      and stroma lamellae. Although grana stacks are highly conserved among land
      plants, the functional relevance of grana stacking remains unclear. Here, we show
      that inhibiting CURT1-mediated alteration of thylakoid ultrastructure in
      Arabidopsis (Arabidopsis thaliana) reduces photosynthetic efficiency and plant
      fitness under adverse, controlled, and natural light conditions. Plants that lack
      CURT1 show less adjustment of grana diameter, which compromises regulatory
      mechanisms like the photosystem II repair cycle and state transitions.
      Interestingly, CURT1A suffices to induce thylakoid membrane curvature in planta
      and thylakoid hyperbending in plants overexpressing CURT1A. We suggest that CURT1
      oligomerization is regulated at the posttranslational level in a light-dependent
      fashion and that CURT1-mediated thylakoid plasticity plays an important role in
      fine-tuning photosynthesis and plant fitness during challenging growth
      conditions.

PMID- 29374110
TI  - If all vets are equal, why the pay gap?

PMID- 29374109
TI  - Neurodevelopment in Young Children Born to HIV-Infected Mothers: A Meta-analysis.
AB  - CONTEXT: HIV-infected (HIV+) children have worse neurodevelopmental outcomes
      compared with HIV-uninfected children. However, little is known regarding the
      differences in neurodevelopment between young HIV+ children, HIV-exposed but
      uninfected (HEU) children, and HIV-unexposed and uninfected (HUU) children.
      OBJECTIVE: To systematically review and meta-analyze data on neurodevelopmental
      performance between young HIV+, HEU, and HUU children. DATA SOURCES: We
      systematically searched the following electronic bibliographic databases: Ovid
      Medline, Embase, PsycINFO, Education Resources Information Center, and the
      Cochrane Database of Systematic Reviews. STUDY SELECTION: Studies were selected
      on the basis of defined inclusion criteria. Titles, abstracts, and full texts
      were assessed by 2 independent reviewers. DATA EXTRACTION: Data were extracted by
      2 independent reviewers and cross-checked by 2 additional reviewers. RESULTS:
      Forty-five studies were identified for inclusion in the systematic review, and of
      these, 11 were included in the meta-analysis on the basis of availability of
      Bayley Scales of Infant and Toddler Development scores. Within the meta-analysis,
      when compared with their HUU peers, HIV+ and HEU children had lower cognitive and
      motor scores. HIV+ and HEU children with antiretroviral (ARV) exposure had lower
      cognitive and motor scores compared with those without ARV exposure. LIMITATIONS:
      We were unable to control adequately for intravenous drug use, geographic
      location, or quality of the assessment independently. CONCLUSIONS: Both HIV+ and
      HEU children had worse developmental outcomes compared with HUU children. HIV+
      and HEU children with ARV exposure also had worse developmental outcomes compared
      with those without exposure; however, these results should be interpreted with
      caution. More research is needed to identify the impact of ARV exposure on young
      children.

PMID- 29374111
TI  - Gender pay gap exists across the profession.

PMID- 29374112
TI  - Avian influenza prevention zone extended.

PMID- 29374113
TI  - Mystery solved for mass mortality event.
AB  - It's been almost three years since over 200,000 saiga antelopes died in central
      Kazakhstan, in a mass mortality event that shocked researchers and wildlife
      experts alike. But now, as Georgina Mills explains, research has revealed that
      there was more to the deaths than first thought.

PMID- 29374114
TI  - Turn talk into action, say animal charities.

PMID- 29374115
TI  - Medicines update.

PMID- 29374118
TI  - Treatment of sheep scab in the UK: preventing the spread of resistant mites.

PMID- 29374119
TI  - How to treat Pseudomonas otitis in dogs.

PMID- 29374121
TI  - Linguatula serrata in an imported Romanian street dog.

PMID- 29374122
TI  - Current status of feline lungworm in the UK.

PMID- 29374123
TI  - Health hazards associated with feeding raw foods.

PMID- 29374124
TI  - The value of good first-opinion practice.

PMID- 29374125
TI  - The value of good first-opinion practice.

PMID- 29374127
TI  - Correction.

PMID- 29374126
TI  - Continuing the campaign on brachycephalic dogs.

PMID- 29374128
TI  - Young scientist award in feline medicine.

PMID- 29374132
TI  - Michael Pittaway.
AB  - A widely respected veterinary surgeon and an innovator within the profession,
      Michael Pittaway was also a man of great charm and huge energy, who applied his
      skills across a wide range of interests.

PMID- 29374135
TI  - Sulfenylation of Human Liver and Kidney Microsomal Cytochromes P450 and Other
      Drug-Metabolizing Enzymes as a Response to Redox Alteration.
AB  - The lumen of the endoplasmic reticulum (ER) provides an oxidizing environment to
      aid in the formation of disulfide bonds, which is tightly regulated by both
      antioxidant proteins and small molecules. On the cytoplasmic side of the ER,
      cytochrome P450 (P450) proteins have been identified as a superfamily of enzymes
      that are important in the formation of endogenous chemicals as well as in the
      detoxication of xenobiotics. Our previous report described oxidative inhibition
      of P450 Family 4 enzymes via oxidation of the heme-thiolate cysteine to a
      sulfenic acid (-SOH) (Albertolle, M. E. et al. (2017) J. Biol. Chem. 292, 11230
      11242). Further proteomic analyses of murine kidney and liver microsomes led to
      the finding that a number of other drug-metabolizing enzymes located in the ER
      are also redox-regulated in this manner. We expanded our analysis of sulfenylated
      enzymes to human liver and kidney microsomes. Evaluation of the sulfenylation,
      catalytic activity, and spectral properties of P450s 1A2, 2C8, 2D6, and 3A4 led
      to the identification of two classes of redox sensitivity in P450 enzymes: heme
      thiolate-sensitive and thiol-insensitive. These findings provide evidence for a
      mammalian P450 regulatory mechanism, which may also be relevant to other drug
      metabolizing enzymes. (Data are available via ProteomeXchange with identifier
      PXD007913.).

PMID- 29374136
TI  - Prepubertal Development of GABAergic Transmission to Gonadotropin-Releasing
      Hormone (GnRH) Neurons and Postsynaptic Response Are Altered by Prenatal
      Androgenization.
AB  - Gonadotropin-releasing hormone (GnRH) neurons regulate reproduction through
      pulsatile GnRH release. Women with polycystic ovary syndrome (PCOS) have
      persistently elevated luteinizing hormone release frequency, reflecting GnRH
      release; this exacerbates hyperandrogenemia and disrupted reproductive cycles
      that are characteristic of this disorder. Clinical evidence suggests that
      neuroendocrine features of PCOS may manifest peripubertally. Adult mice
      prenatally exposed to androgens (PNA) mimic several reproductive features of
      PCOS. GnRH neurons from these mice have increased firing activity and receive
      increased GABAergic transmission, which is excitatory. When changes emerge during
      development is unknown. To study the typical postnatal development of GABAergic
      transmission and the effects of PNA treatment and sex, whole-cell voltage-clamp
      recordings were made of GABAergic postsynaptic currents (PSCs) in GnRH neurons in
      brain slices from prepubertal through adult control and PNA female and male mice.
      GABAergic transmission was present by 1 week of age in females and males and
      increased in frequency, reaching adult levels at 3 and 4 weeks, respectively.
      GABAergic PSC frequency was elevated in 3-week-old PNA versus control females.
      PSC frequency in both controls and PNA mice was activity independent, suggesting
      that PNA induces changes in synapse organization. PNA also alters the functional
      response of GnRH neurons to GABA. GABA induced firing in fewer neurons from 3
      week-old PNA than control females; membrane potential depolarization induced by
      GABA was also reduced in cells from PNA mice at this age. PNA thus induces
      changes during development in the presynaptic organization of the GABAergic
      network afferent to GnRH neurons as well as the postsynaptic GnRH neuron
      response, both of which may contribute to adult reproductive
      dysfunction.SIGNIFICANCE STATEMENT The central neuronal network that regulates
      reproduction is overactive in polycystic ovary syndrome (PCOS), a leading cause
      of infertility. Recent evidence of neuroendocrine dysfunction in midpubertal
      girls suggests that the pathophysiological mechanisms underlying PCOS may arise
      before pubertal maturation. Prenatal exposure to androgens (PNA) in mice mimics
      several neuroendocrine features of PCOS. GABAergic transmission to gonadotropin
      releasing hormone (GnRH) neurons is important for reproduction and is increased
      in adult PNA mice. The typical development of this network and when changes with
      PNA and sex arise relative to puberty are unknown. These studies provide evidence
      that PNA alters prepubertal development of the GABAergic network afferent to GnRH
      neurons, including both the presynaptic organization and postsynaptic response.
      These changes may contribute to reproductive dysfunction in adults.

PMID- 29374137
TI  - Inhalation Frequency Controls Reformatting of Mitral/Tufted Cell Odor
      Representations in the Olfactory Bulb.
AB  - In mammals, olfactory sensation depends on inhalation, which controls activation
      of sensory neurons and temporal patterning of central activity. Odor
      representations by mitral and tufted (MT) cells, the main output from the
      olfactory bulb (OB), reflect sensory input as well as excitation and inhibition
      from OB circuits, which may change as sniff frequency increases. To test the
      impact of sampling frequency on MT cell odor responses, we obtained whole-cell
      recordings from MT cells in anesthetized male and female mice while varying
      inhalation frequency via tracheotomy, allowing comparison of inhalation-linked
      responses across cells. We characterized frequency effects on MT cell responses
      during inhalation of air and odorants using inhalation pulses and also "playback"
      of sniffing recorded from awake mice. Inhalation-linked changes in membrane
      potential were well predicted across frequency from linear convolution of 1 Hz
      responses; and, as frequency increased, near-identical temporal responses could
      emerge from depolarizing, hyperpolarizing, or multiphasic MT responses. However,
      net excitation was not well predicted from 1 Hz responses and varied
      substantially across MT cells, with some cells increasing and others decreasing
      in spike rate. As a result, sustained odorant sampling at higher frequencies led
      to increasing decorrelation of the MT cell population response pattern over time.
      Bulk activation of sensory inputs by optogenetic stimulation affected MT cells
      more uniformly across frequency, suggesting that frequency-dependent
      decorrelation emerges from odor-specific patterns of activity in the OB network.
      These results suggest that sampling behavior alone can reformat early sensory
      representations, possibly to optimize sensory perception during repeated
      sampling.SIGNIFICANCE STATEMENT Olfactory sensation in mammals depends on
      inhalation, which increases in frequency during active sampling of olfactory
      stimuli. We asked how inhalation frequency can shape the neural coding of odor
      information by recording from projection neurons of the olfactory bulb while
      artificially varying odor sampling frequency in the anesthetized mouse. We found
      that sampling an odor at higher frequencies led to diverse changes in net
      responsiveness, as measured by action potential output, that were not predicted
      from low-frequency responses. These changes led to a reorganization of the
      pattern of neural activity evoked by a given odorant that occurred preferentially
      during sustained, high-frequency inhalation. These results point to a novel
      mechanism for modulating early sensory representations solely as a function of
      sampling behavior.

PMID- 29374138
TI  - A Shared Vision for Machine Learning in Neuroscience.
AB  - With ever-increasing advancements in technology, neuroscientists are able to
      collect data in greater volumes and with finer resolution. The bottleneck in
      understanding how the brain works is consequently shifting away from the amount
      and type of data we can collect and toward what we actually do with the data.
      There has been a growing interest in leveraging this vast volume of data across
      levels of analysis, measurement techniques, and experimental paradigms to gain
      more insight into brain function. Such efforts are visible at an international
      scale, with the emergence of big data neuroscience initiatives, such as the BRAIN
      initiative (Bargmann et al., 2014), the Human Brain Project, the Human Connectome
      Project, and the National Institute of Mental Health's Research Domain Criteria
      initiative. With these large-scale projects, much thought has been given to data
      sharing across groups (Poldrack and Gorgolewski, 2014; Sejnowski et al., 2014);
      however, even with such data-sharing initiatives, funding mechanisms, and
      infrastructure, there still exists the challenge of how to cohesively integrate
      all the data. At multiple stages and levels of neuroscience investigation,
      machine learning holds great promise as an addition to the arsenal of analysis
      tools for discovering how the brain works.

PMID- 29374139
TI  - Predictors for Postoperative Loss of Lumbar Lordosis After Long Fusions
      Arthrodesis in Patients with Adult Scoliosis.
AB  - BACKGROUND Loss of lumbar lordosis (LL) is closely related to clinical symptoms
      and operative complications, however, few studies have identified its predictors.
      The purpose of our study was to identify the predictors for loss of LL in
      patients with adult scoliosis and provided evidence for surgical decision-making.
      MATERIAL AND METHODS There were 69 patients with adult scoliosis who underwent
      long fusions arthrodesis from January 2006 to March 2015 included in this
      retrospectively study. The patients were divided into two cohorts according the
      average loss of LL: cohort LL (loss of LL below the average) and cohort GL (loss
      of LL above the average). Multivariate logistic regression analysis and the
      receiver operating characteristic curve were used to identify the predictors.
      RESULTS There were statistically significant differences between the two cohorts
      in preoperative LL (p=0.002), postoperative LL (p=0.036), last follow-up LL
      (p<0.001), postoperative loss LL (p<0.001), preoperative SVA (p=0.007), last
      follow-up SVA (p=0.018), and pelvic incidence (p=0.016). Preoperative LL <23.5
      (OR=0.920, 95% CI=0.870-0.973, p=0.003) and preoperative sagittal vertical axis
      >4.28 (OR=1.199, 95% CI=1.007-1.429, p=0.041) had good accuracy to predict
      postoperative loss of LL. CONCLUSIONS Loss of LL commonly occurred after long
      fusions arthrodesis in patients with adult scoliosis. Postoperative deteriorated
      sagittal balance was more frequently than deteriorated coronal balance.
      Preoperative LL <23.5 and preoperative SVA >4.28 were the predictors for
      postoperative greater loss of LL in patients after long fusions arthrodesis. More
      attention should be paid to how to maintain the LL in patients with preoperative
      predictors, especially if both the identified predictors are present.

PMID- 29374140
TI  - microRNA-874 suppresses tumor proliferation and metastasis in hepatocellular
      carcinoma by targeting the DOR/EGFR/ERK pathway.
AB  - The delta opioid receptor (DOR) is involved in the regulation of malignant
      transformation and tumor progression of hepatocellular carcinoma (HCC). However,
      regulation of the DOR in HCC remains poorly defined. We found that miR-874 was
      identified as a negative regulator of the DOR, which is a direct and functional
      target of miR-874 via its 3' untranslated region (UTR). Moreover, miR-874 was
      downregulated in HCC and its expression was inversely correlated with DOR
      expression. Downregulation of miR-874 was also associated with larger tumor size,
      more vascular invasion, a poor TNM stage, poor tumor differentiation, and
      inferior patient outcomes. Functionally, overexpression of miR-874 in the HCC
      cell line SK-hep-1 inhibited cell growth, migration, in vitro invasion, and in
      vivo tumorigenicity. Furthermore, miR-874 overexpression suppressed the DOR,
      resulting in a downregulated epidermal growth factor receptor (EGFR) and
      extracellular signal-regulated kinase (ERK) phosphorylation. The EGFR activator
      epidermal growth factor (EGF)-can rescue the proliferation and migration
      suppression induced by miR-874 overexpression, and the rescue effects of the EGF
      were blocked by an ERK inhibitor. Our study results suggest that miRNA-874 is a
      negative regulator of the DOR that can suppress tumor proliferation and
      metastasis in HCC by targeting the DOR/EGFR/ERK pathway, which may be a potential
      target for HCC treatment.

PMID- 29374141
TI  - iPSC modeling of severe aplastic anemia reveals impaired differentiation and
      telomere shortening in blood progenitors.
AB  - Aplastic Anemia (AA) is a bone marrow failure (BMF) disorder, resulting in bone
      marrow hypocellularity and peripheral pancytopenia. Severe aplastic anemia (SAA)
      is a subset of AA defined by a more severe phenotype. Although the immunological
      nature of SAA pathogenesis is widely accepted, there is an increasing recognition
      of the role of dysfunctional hematopoietic stem cells in the disease phenotype.
      While pediatric SAA can be attributable to genetic causes, evidence is evolving
      on previously unrecognized genetic etiologies in a proportion of adults with SAA.
      Thus, there is an urgent need to better understand the pathophysiology of SAA,
      which will help to inform the course of disease progression and treatment
      options. We have derived induced pluripotent stem cell (iPSC) from three
      unaffected controls and three SAA patients and have shown that this in vitro
      model mimics two key features of the disease: (1) the failure to maintain
      telomere length during the reprogramming process and hematopoietic
      differentiation resulting in SAA-iPSC and iPSC-derived-hematopoietic progenitors
      with shorter telomeres than controls; (2) the impaired ability of SAA-iPSC
      derived hematopoietic progenitors to give rise to erythroid and myeloid cells.
      While apoptosis and DNA damage response to replicative stress is similar between
      the control and SAA-iPSC-derived-hematopoietic progenitors, the latter show
      impaired proliferation which was not restored by eltrombopag, a drug which has
      been shown to restore hematopoiesis in SAA patients. Together, our data highlight
      the utility of patient specific iPSC in providing a disease model for SAA and
      predicting patient responses to various treatment modalities.

PMID- 29374142
TI  - The BAX/BAK-like protein BOK is a prognostic marker in colorectal cancer.
AB  - The intrinsic or mitochondrial apoptosis pathway is controlled by the interaction
      of antiapoptotic and pro-apoptotic members of the BCL-2 protein family.
      Activation of this death pathway plays a crucial role in cancer progression and
      chemotherapy responses. The BCL-2-related ovarian killer (BOK) possesses three
      BCL-2 homology domains and has been proposed to act in a similar pro-apoptotic
      pathway as the pro-apoptotic proteins BAX and BAK. In this study, we showed that
      stage II and III colorectal cancer patients possessed decreased levels of BOK
      protein in their tumours compared to matched normal tissue. BOK protein levels in
      tumours were also prognostic of clinical outcome but increased BOK protein levels
      surprisingly associated with earlier disease recurrence and reduced overall
      survival. We found no significant association of BOK protein tumour levels with
      ER stress markers GRP78 or GRP94 or with cleaved caspase-3. In contrast, BOK
      protein levels correlated with Calreticulin. These data indicate BOK as a
      prognostic marker in colorectal cancer and suggest that different activities of
      BOK may contribute to cancer progression and prognosis.

PMID- 29374143
TI  - N6-methyladenosine links RNA metabolism to cancer progression.
AB  - N6-methyladenosine (m6A) is the most abundant mRNA modification. With the
      development of antibody-based sequencing technologies and the findings of m6A
      related "writers", "erasers", and "readers", the relationships between m6A and
      mRNA metabolism are emerging. The m6A modification influences almost every step
      of RNA metabolism that comprises mRNA processing, mRNA exporting from nucleus to
      cytoplasm, mRNA translation, mRNA decay, and the biogenesis of long-non-coding
      RNA (lncRNA) and microRNA (miRNA). Recently, more and more studies have found m6A
      is associated with cancer, contributing to the self-renewal of cancer stem cell,
      promotion of cancer cell proliferation, and resistance to radiotherapy or
      chemotherapy. Inhibitors of m6A-related factors have been explored, and some of
      them were identified to inhibit cancer progression, indicating that m6A could be
      a target for cancer therapy. In this review, we are trying to summarize the
      regulation and function of m6A in human carcinogenesis.

PMID- 29374144
TI  - Dual PI3K/mTOR inhibitor BEZ235 as a promising therapeutic strategy against
      paclitaxel-resistant gastric cancer via targeting PI3K/Akt/mTOR pathway.
AB  - Paclitaxel (PTX) is widely used in the front-line chemotherapy for gastric cancer
      (GC), but resistance limits its use. Due to the lack of proper models, mechanisms
      underlying PTX resistance in GC were not well studied. Using established PTX
      resistant GC cell sublines HGC-27R, we for the first time integrated biological
      traits and molecular mechanisms of PTX resistance in GC. Data revealed that PTX
      resistant GC cells were characterized by microtubular disorders, an EMT
      phenotype, reduced responses to antimitotic drugs, and resistance to apoptosis
      (marked by upregulated beta-tubulin III, vimentin, attenuated changes in G2/M
      molecules or pro-apoptotic factors in response to antimitotic drugs or apoptotic
      inducers, respectively). Activation of the phosphoinositide 3-kinase, the
      serine/threonine kinase Akt and mammalian target of rapamycin (PI3K/Akt/mTOR) and
      mitogen-activated protein kinase (MAPK) pathways were also observed, which might
      be the reason for above phenotypic alternations. In vitro data suggested that
      targeting these pathways were sufficient to elicit antitumor responses in PTX
      resistant GC, in which the dual PI3K/mTOR inhibitor BEZ235 displayed higher
      therapeutic efficiency than the mTOR inhibitor everolimus or the MEK inhibitor
      AZD6244. Antitumor effects of BEZ235 were also confirmed in mice bearing HGC-27R
      tumors. Thus, these data suggest that PI3K/Akt/mTOR and MAPK pathway inhibition,
      especially PI3K/mTOR dual blockade, might be a promising therapeutic strategy
      against PTX-resistant GC.

PMID- 29374145
TI  - Human papillomavirus E7 induces p63 expression to modulate DNA damage response.
AB  - Cervical cancer is the third most common malignancy diagnosed in women worldwide.
      The major aetiological factor underlying the malignant transformation of cervical
      cells is the persistent infection with high-risk human papillomaviruses (HR-HPV),
      with more than 99% of cases expressing viral sequences. Here, we report a
      previously unknown mechanism driven by high-risk human papillomavirus E7 protein
      to modulate response to DNA damage in cervical cancer cells. Our data shows that
      HR-HPV E7 oncoprotein induces the transcription of the p53-family member p63,
      which modulates DNA damage response pathways, to facilitate repair of DNA damage.
      Based on our findings, we proposed a model, where HR-HPV could interfere with the
      sensitivity of transformed cells to radiation therapy by modulating DNA damage
      repair efficiency. Importantly, we have shown for the first time a critical role
      for p63 in response to DNA damage in cervical cancer cells.

PMID- 29374146
TI  - Neutralization of CD95 ligand protects the liver against ischemia-reperfusion
      injury and prevents acute liver failure.
AB  - Ischemia-reperfusion injury is a common pathological process in liver surgery and
      transplantation, and has considerable impact on the patient outcome and survival.
      Death receptors are important mediators of ischemia-reperfusion injury, notably
      the signaling pathways of the death receptor CD95 (Apo-1/Fas) and its
      corresponding ligand CD95L. This study investigates, for the first time, whether
      the inhibition of CD95L protects the liver against ischemia-reperfusion injury.
      Warm ischemia was induced in the median and left liver lobes of C57BL/6 mice for
      45 min. CD95Fc, a specific inhibitor of CD95L, was applied prior to ischemia.
      Hepatic injury was assessed via consecutive measurements of liver serum enzymes,
      histopathological assessment of apoptosis and necrosis and caspase assays at 3,
      6, 12, 18 and 24 h after reperfusion. Serum levels of liver enzymes, as well as
      characteristic histopathological changes and caspase assays indicated pronounced
      features of apoptotic and necrotic liver damage 12 and 24 h after ischemia
      reperfusion injury. Animals treated with the CD95L-blocker CD95Fc, exhibited a
      significant reduction in the level of serum liver enzymes and showed both
      decreased histopathological signs of parenchymal damage and decreased caspase
      activation. This study demonstrates that inhibition of CD95L with the CD95L
      blocker CD95Fc, is effective in protecting mice from liver failure due to
      ischemia-reperfusion injury of the liver. CD95Fc could therefore emerge as a new
      pharmacological therapy for liver resection, transplantation surgery and acute
      liver failure.

PMID- 29374147
TI  - Involvement of both caspase-8 and Noxa-activated pathways in endoplasmic
      reticulum stress-induced apoptosis in triple-negative breast tumor cells.
AB  - Recent evidences indicate that triple-negative breast cancer (TNBC) cells with a
      mesenchymal phenotype show a basal activation of the unfolded protein response
      (UPR) that increases their sensitivity to endoplasmic reticulum (ER) stress
      although the underlying cell death mechanism remains largely unexplored. Here we
      show that both caspase-8-dependent and -independent apoptotic mechanisms are
      activated in TNBC cells undergoing sustained ER stress. Activation of the
      extrinsic apoptotic pathway by ER stress involves ATF4-dependent upregulation of
      tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL
      R2/DR5). In addition, accumulation of BH3-only protein Noxa at the mitochondria
      further contributes to apoptosis following ER stress in TNBC cells. Accordingly,
      simultaneous abrogation of both extrinsic and intrinsic apoptotic pathways is
      required to inhibit ER stress-induced apoptosis in these cells. Importantly,
      persistent FLICE-inhibitory protein (FLIP) expression plays an adaptive role to
      prevent early activation of the extrinsic pathway of apoptosis upon ER stress.
      Overall, our data show that ER stress induces cell death through a pleiotropic
      mechanism in TNBC cells and suggest that targeting FLIP expression may be an
      effective approach to sensitize these tumor cells to ER stress-inducing agents.

PMID- 29374148
TI  - Downregulation of annexin A3 inhibits tumor metastasis and decreases drug
      resistance in breast cancer.
AB  - Annexin A3 (ANXA3) is dysregulated and plays an important role in various
      cancers. However, the role of ANXA3 in breast cancer is still unclear. Here, we
      observed that the expression level of ANXA3 was significantly upregulated in
      breast cancer tissues. ANXA3 knockdown inhibited cell invasion but promoted cell
      proliferation in both in vitro and in vivo assays. Furthermore, we found that
      ANXA3 knockdown inhibited the NFkappaB pathway via upregulating IkappaBalpha,
      resulting in mesenchymal-epithelial transition (MET) and a heterogeneity change
      of breast cancer stem cells (BCSCs). In addition, we demonstrated that ANXA3
      knockdown increased the sensitivity of breast cancer cells to doxorubicin by
      increasing the drug uptake. The combination of ANXA3 knockdown and doxorubicin
      treatment simultaneously inhibited tumor growth and metastasis in vivo. This
      study described the role and mechanisms of ANXA3 in regulating BCSCs and breast
      cancer growth and metastasis, indicating that downregulating ANXA3 together with
      chemotherapy might be a novel therapeutic strategy for treating breast cancer.

PMID- 29374149
TI  - FLI1 and PKC co-activation promote highly efficient differentiation of human
      embryonic stem cells into endothelial-like cells.
AB  - Rationale-endothelial cells (ECs) play important roles in various regeneration
      processes and can be used in a variety of therapeutic applications, such as
      cardiac regeneration, gene therapy, tissue-engineered vascular grafts and
      prevascularized tissue transplants. ECs can be acquired from pluripotent and
      adult stem cells. To acquire ECs from human embryonic stem cells (hESCs) in a
      fast, efficient and economic manner. We established a conditional overexpression
      system in hESCs based on 15 transcription factors reported to be responsible for
      hematopoiesis lineage. Among them, only overexpression of FLI1 could induce hESCs
      to a hematopoietic lineage. Moreover, simultaneous overexpression of FLI1 and
      activation of PKC rapidly and efficiently induced differentiation of hESCs into
      induced endothelial cells (iECs) within 3 days, while neither FLI1 overexpression
      nor PKC activation alone could derive iECs from hESCs. During induction, hESCs
      differentiated into spindle-like cells that were consistent in appearance with
      ECs. Flow cytometric analysis revealed that 92.2-98.9% and 87.2-92.6% of these
      cells were CD31+ and CD144+, respectively. Expression of vascular-specific genes
      dramatically increased, while the expression of pluripotency genes gradually
      decreased during induction. iECs incorporated acetylated low-density
      lipoproteins, strongly expressed vWF and bound UEA-1. iECs also formed capillary
      like structures both in vitro and in vivo. RNA-seq analysis verified that these
      cells closely resembled their in vivo counterparts. Our results showed that co
      activation of FLI1 and PKC could induce differentiation of hESCs into iECs in a
      fast, efficient and economic manner.

PMID- 29374150
TI  - Primed atypical ductal hyperplasia-associated fibroblasts promote cell growth and
      polarity changes of transformed epithelium-like breast cancer MCF-7 cells via miR
      200b/c-IKKbeta signaling.
AB  - Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating cancer
      cell proliferation, and invasion, but how the premalignant stromal fibroblasts
      trigger epithelial changes remain unclear. We demonstrate that atypical ductal
      hyperplasia-associated fibroblasts (AHFs) are one kind of activated fibroblasts
      and stimulate cell growth and polarity change of epithelium-like tumor cell MCF-7
      as CAFs-like fibroblasts. Microarray shows miR-200b and miR-200c are
      downregulated during AHFs and CAFs, and contribute to stromal fibroblast
      activity. Additionally, miR-200b/c with target gene IKKbeta (inhibitor of nuclear
      factor kappa-B kinase beta) control PAI-1 (plasminogen activator inhibitor-1)
      expression to regulate growth and polarity changes of MCF-7 cells through NF
      kappaB pathway. Exploring the difference of AHFs in premalignant transformation
      is crucial for understanding the pathobiology of breast cancer progression.

PMID- 29374151
TI  - Beyond a phenomenological description of magnetostriction.
AB  - Magnetostriction, the strain induced by a change in magnetization, is a universal
      effect in magnetic materials. Owing to the difficulty in unraveling its
      microscopic origin, it has been largely treated phenomenologically. Here, we show
      how the source of magnetostriction-the underlying magnetoelastic stress-can be
      separated in the time domain, opening the door for an atomistic understanding. X
      ray and electron diffraction are used to separate the sub-picosecond spin and
      lattice responses of FePt nanoparticles. Following excitation with a 50-fs laser
      pulse, time-resolved X-ray diffraction demonstrates that magnetic order is lost
      within the nanoparticles with a time constant of 146 fs. Ultrafast electron
      diffraction reveals that this demagnetization is followed by an anisotropic,
      three-dimensional lattice motion. Analysis of the size, speed, and symmetry of
      the lattice motion, together with ab initio calculations accounting for the
      stresses due to electrons and phonons, allow us to reveal the magnetoelastic
      stress generated by demagnetization.

PMID- 29374152
TI  - Distinct epigenetic programs regulate cardiac myocyte development and disease in
      the human heart in vivo.
AB  - Epigenetic mechanisms and transcription factor networks essential for
      differentiation of cardiac myocytes have been uncovered. However, reshaping of
      the epigenome of these terminally differentiated cells during fetal development,
      postnatal maturation, and in disease remains unknown. Here, we investigate the
      dynamics of the cardiac myocyte epigenome during development and in chronic heart
      failure. We find that prenatal development and postnatal maturation are
      characterized by a cooperation of active CpG methylation and histone marks at cis
      regulatory and genic regions to shape the cardiac myocyte transcriptome. In
      contrast, pathological gene expression in terminal heart failure is accompanied
      by changes in active histone marks without major alterations in CpG methylation
      and repressive chromatin marks. Notably, cis-regulatory regions in cardiac
      myocytes are significantly enriched for cardiovascular disease-associated
      variants. This study uncovers distinct layers of epigenetic regulation not only
      during prenatal development and postnatal maturation but also in diseased human
      cardiac myocytes.

PMID- 29374153
TI  - Gamma and beta bursts during working memory readout suggest roles in its
      volitional control.
AB  - Working memory (WM) activity is not as stationary or sustained as previously
      thought. There are brief bursts of gamma (~50-120 Hz) and beta (~20-35 Hz)
      oscillations, the former linked to stimulus information in spiking. We examined
      these dynamics in relation to readout and control mechanisms of WM. Monkeys held
      sequences of two objects in WM to match to subsequent sequences. Changes in beta
      and gamma bursting suggested their distinct roles. In anticipation of having to
      use an object for the match decision, there was an increase in gamma and spiking
      information about that object and reduced beta bursting. This readout signal was
      only seen before relevant test objects, and was related to premotor activity.
      When the objects were no longer needed, beta increased and gamma decreased
      together with object spiking information. Deviations from these dynamics
      predicted behavioral errors. Thus, beta could regulate gamma and the information
      in WM.

PMID- 29374154
TI  - SIRT1 induces epithelial-mesenchymal transition by promoting autophagic
      degradation of E-cadherin in melanoma cells.
AB  - Melanoma is highly metastatic, and understanding of its molecular mechanism is
      urgently needed for the development of therapeutic targets and prognostic
      assessment for metastatic melanoma. SIRT1 is a nicotinamide adenine dinucleotide
      (NAD+)-dependent protein deacetylase, belonging to the mammalian sirtuin family.
      It has been reported that SIRT1 is associated with metastasis in various cancers.
      However, the molecular mechanism of SIRT1 in melanoma metastasis remains to be
      clarified. Here we report that SIRT1 induces the epithelial-mesenchymal
      transition (EMT) by accelerating E-cadherin degradation via autophagy and
      facilitates melanoma metastasis. Initially, we found that SIRT1 expression was
      frequently elevated in metastatic melanoma compared with primary melanoma. In
      addition, SIRT1 induced the EMT and promoted cell migration and invasion by
      decreasing E-cadherin expression. Further work demonstrated that SIRT1
      accelerated the autophagic degradation of E-cadherin through deacetylation of
      Beclin 1. In addition, inhibition of autophagy recovered E-cadherin expression
      and suppressed cell migration and invasion by delaying the degradation of E
      cadherin in SIRT1-overexpressing cells. Overall, our findings reveal a novel
      molecular mechanism for SIRT1 in melanoma metastasis, indicating that SIRT1 may
      serve as a viable therapeutic target for metastatic melanoma.

PMID- 29374155
TI  - Kruppel-like factor 4-dependent Staufen1-mediated mRNA decay regulates cortical
      neurogenesis.
AB  - Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a
      critical role in diverse cellular physiology. While most of these functions
      attribute to its role as a transcription factor, it is postulated that Klf4 may
      play a role other than transcriptional regulation. Here we demonstrate that Klf4
      loss in neural progenitor cells (NPCs) leads to increased neurogenesis and
      reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding
      protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a
      complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1
      recruitment to the 3'-untranslated region of neurogenesis-associated mRNAs,
      increasing Stau1-mediated mRNA decay (SMD) of these transcripts. Stau1 depletion
      abrogated SMD of target mRNAs and rescued neurogenesis defects in Klf4
      overexpressing NPCs. Furthermore, Ddx5/17 knockdown significantly blocked Klf4
      mediated mRNA degradation. Our results highlight a novel molecular mechanism
      underlying stability of neurogenesis-associated mRNAs controlled by the
      Klf4/Ddx5/17/Stau1 axis during mammalian corticogenesis.

PMID- 29374156
TI  - Caging tin oxide in three-dimensional graphene networks for superior volumetric
      lithium storage.
AB  - Tin and its compounds hold promise for the development of high-capacity anode
      materials that could replace graphitic carbon used in current lithium-ion
      batteries. However, the introduced porosity in current electrode designs to
      buffer the volume changes of active materials during cycling does not afford high
      volumetric performance. Here, we show a strategy leveraging a sulfur sacrificial
      agent for controlled utility of void space in a tin oxide/graphene composite
      anode. In a typical synthesis using the capillary drying of graphene hydrogels,
      sulfur is employed with hard tin oxide nanoparticles inside the contraction
      hydrogels. The resultant graphene-caged tin oxide delivers an ultrahigh
      volumetric capacity of 2123 mAh cm-3 together with good cycling stability. Our
      results suggest not only a conversion-type composite anode that allows for good
      electrochemical characteristics, but also a general synthetic means to
      engineering the packing density of graphene nanosheets for high energy storage
      capabilities in small volumes.

PMID- 29374157
TI  - Targeting EHMT2 reverses EGFR-TKI resistance in NSCLC by epigenetically
      regulating the PTEN/AKT signaling pathway.
AB  - Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance
      is a major obstacle in the treatment of non-small cell lung cancer (NSCLC).
      Epigenetic alterations have been shown to be involved in NSCLC oncogenesis;
      however, their function in EGFR-TKI resistance remains uncharacterized. Here, we
      found that an EHMT2 inhibitor, UNC0638, can significantly inhibit cell growth and
      induce apoptosis in EGFR-TKI-resistant NSCLC cells. Additionally, we also found
      that EHMT2 expression and enzymatic activity levels were elevated in EGFR-TKI
      resistant NSCLC cells. Moreover, we determined that genetic or pharmacological
      inhibition of EHMT2 expression enhanced TKI sensitivity and suppressed migration
      and tumor sphere formation in EGFR-TKI-resistant NSCLC cells. Further
      investigation revealed that EHMT2 contributed to PTEN transcriptional repression
      and thus facilitated AKT pathway activation. The negative relationship between
      EHMT2 and PTEN was confirmed by our clinical study. Furthermore, we determined
      that combination treatment with the EHMT2 inhibitor and Erlotinib resulted in
      enhanced antitumor effects in a preclinical EGFR-TKI-resistance model. We also
      found that high EHMT2 expression along with low PTEN expression can predict poor
      overall survival in patients with NSCLC. In summary, our findings showed that
      EHMT2 facilitated EGFR-TKI resistance by regulating the PTEN/AKT pathway in NSCLC
      cells, suggesting that EHMT2 may be a target in the clinical treatment of EGFR
      TKI-resistant NSCLC.

PMID- 29374158
TI  - Global observations of reflectors in the mid-mantle with implications for mantle
      structure and dynamics.
AB  - Seismic tomography indicates that flow is commonly deflected in the mid-mantle.
      However, without a candidate mineral phase change, causative mechanisms remain
      controversial. Deflection of flow has been linked to radial changes in viscosity
      and/or composition, but a lack of global observations precludes comprehensive
      tests by seismically detectable features. Here we perform a systematic global
      scale interrogation of mid-mantle seismic reflectors with lateral size 500-2000
      km and depths 800-1300 km. Reflectors are detected globally with variable depth,
      lateral extent and seismic polarity and identify three distinct seismic domains
      in the mid-mantle. Near-absence of reflectors in seismically fast regions may
      relate to dominantly subvertical heterogeneous slab material or small impedance
      contrasts. Seismically slow thermochemical piles beneath the Pacific generate
      numerous reflections. Large reflectors at multiple depths within neutral regions
      possibly signify a compositional or textural transition, potentially linked to
      long-term slab stagnation. This variety of reflector properties indicates
      widespread compositional heterogeneity at mid-mantle depths.

PMID- 29374159
TI  - The responsively decreased PKM2 facilitates the survival of pancreatic cancer
      cells in hypoglucose.
AB  - Cancer cells predominantly produce energy at a high rate of glycolysis even in
      aerobic environment. It is termed as Warburg effect and is necessary for the
      tumorigenesis. Studies showed pyruvate kinase M2 (PKM2), a key regulator of the
      Warburg effect, is overexpressed and involved in numerous cancers. However, the
      expression and function of PKM2 in pancreatic cancer (PC) remain undefined. Our
      results showed that PKM2 is overexpressed in the PC tissue compared to the
      peritumoral tissue. Unexpected, the downregulation of PKM2 did not affect the
      proliferation, invasion, and chemoresistance of PC cells. Since pancreatic cancer
      is a hypovascular tumor with comparably insufficient energy supply, we further
      investigate the relationship between PKM2 and hypoglucose. Interestingly, we
      further discovered that decreased expression of PKM2 was detected in PC samples
      with lower microvessel density as well as in PC cells treated with hypoglucose
      condition (0.5 mM). Furthermore, the downregulation of PKM2 facilitated, while
      the upregulation of PKM2 inhibited, PC cells survival during hypoglucose. We
      further revealed that the repressed PKM2 induced autophagy, high NADPH/NADP
      ratio, and biomacromolecule production, but reduced ROS accumulation. Moreover,
      AMPKalpha1 knockdown repressed the autophagy and survival of PC cells during
      hypoglucose, which were promoted by PKM2 knockdown. Collectively, our study
      indicates that decreased PKM2 diverts glucose metabolism to biomacromolecule
      accumulation and antioxidants generation during glucose deprivation. This
      metabolism alteration elevates AMPKalpha1-dependent autophagy, which facilitates
      PC cell survival during glucose deprivation. Therefore, functions of PKM2 are
      complicated and cannot be defined as oversimplified promoter or inhibitor in PC.

PMID- 29374160
TI  - Dendritic core-shell nickel-iron-copper metal/metal oxide electrode for efficient
      electrocatalytic water oxidation.
AB  - Electrochemical water splitting requires efficient water oxidation catalysts to
      accelerate the sluggish kinetics of water oxidation reaction. Here, we report a
      promisingly dendritic core-shell nickel-iron-copper metal/metal oxide electrode,
      prepared via dealloying with an electrodeposited nickel-iron-copper alloy as a
      precursor, as the catalyst for water oxidation. The as-prepared core-shell nickel
      iron-copper electrode is characterized with porous oxide shells and metallic
      cores. This tri-metal-based core-shell nickel-iron-copper electrode exhibits a
      remarkable activity toward water oxidation in alkaline medium with an
      overpotential of only 180 mV at a current density of 10 mA cm-2. The core-shell
      NiFeCu electrode exhibits pH-dependent oxygen evolution reaction activity on the
      reversible hydrogen electrode scale, suggesting that non-concerted proton
      electron transfers participate in catalyzing the oxygen evolution reaction. To
      the best of our knowledge, the as-fabricated core-shell nickel-iron-copper is one
      of the most promising oxygen evolution catalysts.

PMID- 29374161
TI  - Female sexual behavior in mice is controlled by kisspeptin neurons.
AB  - Sexual behavior is essential for the survival of many species. In female rodents,
      mate preference and copulatory behavior depend on pheromones and are synchronized
      with ovulation to ensure reproductive success. The neural circuits driving this
      orchestration in the brain have, however, remained elusive. Here, we demonstrate
      that neurons controlling ovulation in the mammalian brain are at the core of a
      branching neural circuit governing both mate preference and copulatory behavior.
      We show that male odors detected in the vomeronasal organ activate kisspeptin
      neurons in female mice. Classical kisspeptin/Kiss1R signaling subsequently
      triggers olfactory-driven mate preference. In contrast, copulatory behavior is
      elicited by kisspeptin neurons in a parallel circuit independent of Kiss1R
      involving nitric oxide signaling. Consistent with this, we find that kisspeptin
      neurons impinge onto nitric oxide-synthesizing neurons in the ventromedial
      hypothalamus. Our data establish kisspeptin neurons as a central regulatory hub
      orchestrating sexual behavior in the female mouse brain.

PMID- 29374162
TI  - A dual role for the N-terminal domain of the IL-3 receptor in cell signalling.
AB  - The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the
      haemopoietic, vascular and immune systems and is overexpressed in acute and
      chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine
      receptor family in which the alpha-subunits consist of two fibronectin III-like
      domains that bind cytokine, and a third, evolutionarily unrelated and
      topologically conserved, N-terminal domain (NTD) with unknown function. Here we
      show by crystallography that, while the NTD of IL3Ralpha is highly mobile in the
      presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W.
      Mutagenesis, biochemical and functional studies show that the NTD of IL3Ralpha
      regulates IL-3 binding and signalling and reveal an unexpected role in preventing
      spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in
      this cytokine receptor family, protecting against inappropriate signalling and
      dynamically regulating cytokine receptor binding and function.

PMID- 29374163
TI  - Mitochondrial levels determine variability in cell death by modulating apoptotic
      gene expression.
AB  - Fractional killing is the main cause of tumour resistance to chemotherapy. This
      phenomenon is observed even in genetically identical cancer cells in homogeneous
      microenvironments. To understand this variable resistance, here we investigate
      the individual responses to TRAIL in a clonal population of HeLa cells using live
      cell microscopy and computational modelling. We show that the cellular
      mitochondrial content determines the apoptotic fate and modulates the time to
      death, cells with higher mitochondrial content are more prone to die. We find
      that all apoptotic protein levels are modulated by the mitochondrial content.
      Modelling the apoptotic network, we demonstrate that these correlations, and
      especially the differential control of anti- and pro-apoptotic protein pairs,
      confer mitochondria a powerful discriminatory capacity of apoptotic fate. We find
      a similar correlation between the mitochondria and apoptotic proteins in colon
      cancer biopsies. Our results reveal a different role of mitochondria in apoptosis
      as the global regulator of apoptotic protein expression.

PMID- 29374164
TI  - Molecular snapshots of APE1 proofreading mismatches and removing DNA damage.
AB  - Human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is an essential DNA repair
      enzyme which uses a single active site to process DNA damage via two distinct
      activities: (1) AP-endonuclease and (2) 3' to 5' exonuclease. The AP-endonuclease
      activity cleaves at AP-sites, while the exonuclease activity excises bulkier 3'
      mismatches and DNA damage to generate clean DNA ends suitable for downstream
      repair. Molecular details of the exonuclease reaction and how one active site can
      accommodate various toxic DNA repair intermediates remains elusive despite being
      biologically important. Here, we report multiple high-resolution APE1-DNA
      structural snapshots revealing how APE1 removes 3' mismatches and DNA damage by
      placing the 3' group within the intra-helical DNA cavity via a non-base flipping
      mechanism. This process is facilitated by a DNA nick, instability of a
      mismatched/damaged base, and bending of the DNA. These results illustrate how
      APE1 cleanses DNA dirty-ends to generate suitable substrates for downstream
      repair enzymes.

PMID- 29374166
TI  - Pronounced centennial-scale Atlantic Ocean climate variability correlated with
      Western Hemisphere hydroclimate.
AB  - Surface-ocean circulation in the northern Atlantic Ocean influences Northern
      Hemisphere climate. Century-scale circulation variability in the Atlantic Ocean,
      however, is poorly constrained due to insufficiently-resolved paleoceanographic
      records. Here we present a replicated reconstruction of sea-surface temperature
      and salinity from a site sensitive to North Atlantic circulation in the Gulf of
      Mexico which reveals pronounced centennial-scale variability over the late
      Holocene. We find significant correlations on these timescales between salinity
      changes in the Atlantic, a diagnostic parameter of circulation, and widespread
      precipitation anomalies using three approaches: multiproxy synthesis,
      observational datasets, and a transient simulation. Our results demonstrate links
      between centennial changes in northern Atlantic surface-circulation and
      hydroclimate changes in the adjacent continents over the late Holocene. Notably,
      our findings reveal that weakened surface-circulation in the Atlantic Ocean was
      concomitant with well-documented rainfall anomalies in the Western Hemisphere
      during the Little Ice Age.

PMID- 29374165
TI  - Automated NMR resonance assignments and structure determination using a minimal
      set of 4D spectra.
AB  - Automated methods for NMR structure determination of proteins are continuously
      becoming more robust. However, current methods addressing larger, more complex
      targets rely on analyzing 6-10 complementary spectra, suggesting the need for
      alternative approaches. Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete
      pipeline for NOE-driven structure determination of medium- to larger-sized
      proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a
      single, fully protonated protein sample in an iterative ansatz where common NOEs
      between different spin systems supplement conventional through-bond
      connectivities to establish assignments of sidechain and backbone resonances at
      high levels of completeness and with a minimum error rate. The 4D-CHAINS
      assignments are then used to guide automated assignment of long-range NOEs and
      structure refinement in autoNOE-Rosetta. Our results on four targets ranging in
      size from 15.5 to 27.3 kDa illustrate that the structures of proteins can be
      determined accurately and in an unsupervised manner in a matter of days.

PMID- 29374167
TI  - Discovery of new molecular entities able to strongly interfere with Hsp90 C
      terminal domain.
AB  - Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone deeply
      involved in the complex network of cellular signaling governing some key
      functions, such as cell proliferation and survival, invasion and angiogenesis.
      Over the past years the N-terminal protein domain has been fully investigated as
      attractive strategy against cancer, but despite the many efforts lavished in the
      field, none of the N-terminal binders (termed "classical inhibitors"), currently
      in clinical trials, have yet successfully reached the market, because of the
      detrimental heat shock response (HSR) that showed to induce; thus, recently, the
      selective inhibition of Hsp90 C-terminal domain has powerfully emerged as a more
      promising alternative strategy for anti-cancer therapy, not eliciting this cell
      rescue cascade. However, the structural complexity of the target protein and,
      mostly, the lack of a co-crystal structure of C-terminal domain-ligand, essential
      to drive the identification of new hits, represent the largest hurdles in the
      development of new selective C-terminal inhibitors. Continuing our investigations
      on the identification of new anticancer drug candidates, by using an orthogonal
      screening approach, here we describe two new potent C-terminal inhibitors able to
      induce cancer cell death and a considerable down-regulation of Hsp90 client
      oncoproteins, without triggering the undesired heat shock response.

PMID- 29374168
TI  - Downregulation of MCL-1 and upregulation of PUMA using mTOR inhibitors enhance
      antitumor efficacy of BH3 mimetics in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) shows a higher malignant and poorer clinical
      outcome compared with other breast cancer subtypes. Albeit that chemotherapy is
      the first choice for TNBC treatment, rapid emergence of chemoresistance and
      variability of chemotherapeutic responses in TNBC patients call for novel
      therapeutic strategies. Here, we reported evidences highlighting that combination
      of BH3 mimetics and mTOR inhibitors could be a promising therapeutic strategy to
      improve TNBC treatment. Our results showed that combination of the BH3 mimetic
      ABT263 and typical mTOR inhibitors, BEZ235 or AZD8055, leads to efficient
      apoptosis in vitro. Tumor regression was significantly improved by combination
      therapy compared with either drug alone in the xenograft model. Further
      mechanistic investigations revealed that mTOR inhibitors induced the suppression
      of MCL-1; concomitantly, the expression level of PUMA was significantly
      upregulated in a FOXO3a-dependent manner. The specific changes of MCL-1 and PUMA
      facilitated the release of the apoptotic regulators, such as BIM, BAX, and BAK,
      to induce the activation of mitochondrial apoptotic pathway, thereby sensitizing
      the ABT263 activity in TNBC. Therefore, our findings provided evidences that mTOR
      inhibitors can enhance antitumor efficacy of BH3 mimetics via downregulating MCL
      1 and upregulating PUMA in TNBC; it could be a promising therapeutic strategy to
      treat TNBC.

PMID- 29374169
TI  - Strong indirect coupling between graphene-based mechanical resonators via a
      phonon cavity.
AB  - Mechanical resonators are promising systems for storing and manipulating
      information. To transfer information between mechanical modes, either direct
      coupling or an interface between these modes is needed. In previous works, strong
      coupling between different modes in a single mechanical resonator and direct
      interaction between neighboring mechanical resonators have been demonstrated.
      However, coupling between distant mechanical resonators, which is a crucial
      request for long-distance classical and quantum information processing using
      mechanical devices, remains an experimental challenge. Here, we report the
      experimental observation of strong indirect coupling between separated mechanical
      resonators in a graphene-based electromechanical system. The coupling is mediated
      by a far-off-resonant phonon cavity through virtual excitations via a Raman-like
      process. By controlling the resonant frequency of the phonon cavity, the indirect
      coupling can be tuned in a wide range. Our results may lead to the development of
      gate-controlled all-mechanical devices and open up the possibility of long
      distance quantum mechanical experiments.

PMID- 29374170
TI  - Room temperature magneto-optic effect in silicon light-emitting diodes.
AB  - In weakly spin-orbit coupled materials, the spin-selective nature of
      recombination can give rise to large magnetic-field effects, e.g. on the electro
      luminescence of molecular semiconductors. Although silicon has weak spin-orbit
      coupling, observing spin-dependent recombination through magneto
      electroluminescence is challenging: silicon's indirect band-gap causes an
      inefficient emission and it is difficult to separate spin-dependent phenomena
      from classical magneto-resistance effects. Here we overcome these challenges and
      measure magneto-electroluminescence in silicon light-emitting diodes fabricated
      via gas immersion laser doping. These devices allow us to achieve efficient
      emission while retaining a well-defined geometry, thus suppressing classical
      magnetoresistance effects to a few percent. We find that electroluminescence can
      be enhanced by up to 300% near room temperature in a seven Tesla magnetic field,
      showing that the control of the spin degree of freedom can have a strong impact
      on the efficiency of silicon LEDs.

PMID- 29374171
TI  - Lipopolysaccharide O-antigen delays plant innate immune recognition of Xylella
      fastidiosa.
AB  - Lipopolysaccharides (LPS) are among the known pathogen-associated molecular
      patterns (PAMPs). LPSs are potent elicitors of PAMP-triggered immunity (PTI), and
      bacteria have evolved intricate mechanisms to dampen PTI. Here we demonstrate
      that Xylella fastidiosa (Xf), a hemibiotrophic plant pathogenic bacterium,
      possesses a long chain O-antigen that enables it to delay initial plant
      recognition, thereby allowing it to effectively skirt initial elicitation of
      innate immunity and establish itself in the host. Lack of the O-antigen modifies
      plant perception of Xf and enables elicitation of hallmarks of PTI, such as ROS
      production specifically in the plant xylem tissue compartment, a tissue not
      traditionally considered a spatial location of PTI. To explore translational
      applications of our findings, we demonstrate that pre-treatment of plants with Xf
      LPS primes grapevine defenses to confer tolerance to Xf challenge.

PMID- 29374172
TI  - Subcortical evidence for a contribution of arousal to fMRI studies of brain
      activity.
AB  - Cortical activity during periods of rest is punctuated by widespread, synchronous
      events in both electrophysiological and hemodynamic signals, but their behavioral
      relevance remains unclear. Here we report that these events correspond to
      momentary drops in cortical arousal and are associated with activity changes in
      the basal forebrain and thalamus. Combining fMRI and electrophysiology in
      macaques, we first establish that fMRI transients co-occur with spectral shifts
      in local field potentials (LFPs) toward low frequencies. Applying this knowledge
      to fMRI data from the human connectome project, we find that the fMRI transients
      are strongest in sensory cortices. Surprisingly, the positive cortical transients
      occur together with negative transients in focal subcortical areas known to be
      involved with arousal regulation, most notably the basal forebrain. This
      subcortical involvement, combined with the prototypical pattern of LFP spectral
      shifts, suggests that commonly observed widespread variations in fMRI cortical
      activity are associated with momentary drops in arousal.

PMID- 29374174
TI  - Generalized Fano lineshapes reveal exceptional points in photonic molecules.
AB  - The optical behavior of coupled systems, in which the breaking of parity and time
      reversal symmetry occurs, is drawing increasing attention to address the physics
      of the exceptional point singularity, i.e., when the real and imaginary parts of
      the normal-mode eigenfrequencies coincide. At this stage, fascinating phenomena
      are predicted, including electromagnetic-induced transparency and phase
      transitions. To experimentally observe the exceptional points, the near-field
      coupling to waveguide proposed so far was proved to work only in peculiar cases.
      Here, we extend the interference detection scheme, which lies at the heart of the
      Fano lineshape, by introducing generalized Fano lineshapes as a signature of the
      exceptional point occurrence in resonant-scattering experiments. We investigate
      photonic molecules and necklace states in disordered media by means of a near
      field hyperspectral mapping. Generalized Fano profiles in material science could
      extend the characterization of composite nanoresonators, semiconductor
      nanostructures, and plasmonic and metamaterial devices.

PMID- 29374173
TI  - Differential coding of reward and movement information in the dorsomedial
      striatal direct and indirect pathways.
AB  - The direct and indirect pathways of the basal ganglia have long been thought to
      mediate behavioral promotion and inhibition, respectively. However, this classic
      dichotomous model has been recently challenged. To better understand neural
      processes underlying reward-based learning and movement control, we recorded from
      direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in the
      dorsomedial striatum of D1-Cre and D2-Cre mice performing a probabilistic
      Pavlovian conditioning task. dSPNs tend to increase activity while iSPNs decrease
      activity as a function of reward value, suggesting the striatum represents value
      in the relative activity levels of dSPNs versus iSPNs. Lick offset-related
      activity increase is largely dSPN selective, suggesting dSPN involvement in
      suppressing ongoing licking behavior. Rapid responses to negative outcome and
      previous reward-related responses are more frequent among iSPNs than dSPNs,
      suggesting stronger contributions of iSPNs to outcome-dependent behavioral
      adjustment. These findings provide new insights into striatal neural circuit
      operations.

PMID- 29374176
TI  - Decadal climate predictability in the southern Indian Ocean captured by SINTEX-F
      using a simple SST-nudging scheme.
AB  - Decadal climate variability in the southern Indian Ocean has great influences on
      southern African climate through modulation of atmospheric circulation. Although
      many efforts have been made to understanding physical mechanisms, predictability
      of the decadal climate variability, in particular, the internally generated
      variability independent from external atmospheric forcing, remains poorly
      understood. This study investigates predictability of the decadal climate
      variability in the southern Indian Ocean using a coupled general circulation
      model, called SINTEX-F. The ensemble members of the decadal reforecast
      experiments were initialized with a simple sea surface temperature (SST) nudging
      scheme. The observed positive and negative peaks during late 1990s and late 2000s
      are well reproduced in the reforecast experiments initiated from 1994 and 1999,
      respectively. The experiments initiated from 1994 successfully capture warm SST
      and high sea level pressure anomalies propagating from the South Atlantic to the
      southern Indian Ocean. Also, the other experiments initiated from 1999 skillfully
      predict phase change from a positive to negative peak. These results suggest that
      the SST-nudging initialization has the essence to capture the predictability of
      the internally generated decadal climate variability in the southern Indian
      Ocean.

PMID- 29374175
TI  - Three-dimensional reconstruction and NURBS-based structured meshing of coronary
      arteries from the conventional X-ray angiography projection images.
AB  - Despite its two-dimensional nature, X-ray angiography (XRA) has served as the
      gold standard imaging technique in the interventional cardiology for over five
      decades. Accordingly, demands for tools that could increase efficiency of the XRA
      procedure for the quantitative analysis of coronary arteries (CA) are constantly
      increasing. The aim of this study was to propose a novel procedure for three
      dimensional modeling of CA from uncalibrated XRA projections. A comprehensive
      mathematical model of the image formation was developed and used with a robust
      genetic algorithm optimizer to determine the calibration parameters across XRA
      views. The frames correspondences between XRA acquisitions were found using a
      partial-matching approach. Using the same matching method, an efficient procedure
      for vessel centerline reconstruction was developed. Finally, the problem of
      meshing complex CA trees was simplified to independent reconstruction and meshing
      of connected branches using the proposed nonuniform rational B-spline (NURBS)
      based method. Because it enables structured quadrilateral and hexahedral meshing,
      our method is suitable for the subsequent computational modelling of CA
      physiology (i.e. coronary blood flow, fractional flow reverse, virtual stenting
      and plaque progression). Extensive validations using digital, physical, and
      clinical datasets showed competitive performances and potential for further
      application on a wider scale.

PMID- 29374177
TI  - Nanopillars with E-field accessible multi-state (N >= 4) magnetization having
      giant magnetization changes in self-assembled BiFeO3-CoFe2O4/Pb(Mg1/3Nb2/3)
      38at%PbTiO3 heterostructures.
AB  - We have deposited self-assembled BiFeO3-CoFe2O4 (BFO-CFO) thin films on (100)
      oriented SrRuO3-buffered Pb(Mg1/3Nb2/3)0.62Ti0.38O3 (PMN-38PT) single crystal
      substrates. These heterostructures were used for the study of real-time changes
      in the magnetization with applied DC electric field (E DC ). With increasing E DC
      , a giant magnetization change was observed along the out-of-plane (easy) axis.
      The induced magnetization changes of the CFO nanopillars in the BFO/CFO layer
      were about DeltaM/M rDC  = 93% at E DC  = -3 kv/cm. A giant converse
      magnetoelectric (CME) coefficient of 1.3 * 10-7 s/m was estimated from the data.
      By changing E DC , we found multiple(N >= 4) unique possible values of a stable
      magnetization with memory on the removal of the field.

PMID- 29374179
TI  - High-resolution patterning of solution-processable materials via externally
      engineered pinning of capillary bridges.
AB  - Electronics based on solution-processable materials are promising for
      applications in many fields which stimulated enormous research interest in liquid
      drying and pattern formation. However, assembling of structure with
      submicrometre/nanometre resolution through liquid process is very challenging. We
      show a simple method to rapidly generate polymer structures with deep
      submicrometre-sized features over large areas. In this method, a solution film is
      dried on a substrate under a suspended flexible template with groove/ridge
      surface topography. Upon solvent evaporation, the solution splits in the grooves
      and forms capillary bridges between the template and substrate, which are firmly
      pinned by the edges of the template grooves. This groove pinning stabilizes the
      contact lines, thereby allowing the formation of fine patterned structures with
      high aspect ratios which were used to fabricate various functional materials and
      electronic devices. We also produced secondary self-assembled nano-stripe
      patterns with resolutions of about 50 nm on the primary lines.

PMID- 29374180
TI  - c-FLIP is a target of the E3 ligase deltex1 in gastric cancer.
AB  - The ubiquitin E3 ligase DELTEX1 (DTX1) is specifically downregulated in gastric
      cancer tissues, and expression of DTX1 is linked to better prognoses and survival
      in gastric cancer. Cellular FLICE inhibitory protein (c-FLIP) is known for its
      pivotal role in the resistance of cancer cells to death receptor-induced cell
      death. Here, we show that DTX1 is an E3 ligase for c-FLIP in gastric cancer
      cells. DTX1 promoted c-FLIP downregulation. Overexpression of DTX1 sensitized
      gastric cancer cells to TRAIL-induced apoptosis, whereas DTX1-knockdown
      attenuated apoptosis induction. DTX1 binds c-FLIPL and directs it into the
      endosome-lysosomal pathway for proteasome-independent degradation. Moreover,
      induction of DTX1 in AGS cells by geldanamycin conferred susceptibility of those
      cells to TRAIL-induced apoptosis. Our results reveal a tumor-suppressive role for
      DTX1 and suggest a new approach to increasing TRAIL efficacy by raising DTX1
      levels in gastric cancer therapy. DTX1 also enhanced c-FLIP degradation and FasL
      induced and TRAIL-induced apoptosis in T cells, suggesting that DTX1 constitutes
      one of the physiological mechanisms regulating c-FLIP stability.

PMID- 29374178
TI  - Characterizing hepatitis C virus epidemiology in Egypt: systematic reviews, meta
      analyses, and meta-regressions.
AB  - Egypt is the most affected nation by hepatitis C virus (HCV) and needs a
      comprehensive characterization of HCV epidemiology to inform the scale-up of
      treatment and prevention programs. Systematic reviews, meta-analyses, and meta
      regressions were conducted. A total of 25 incidence, 259 prevalence, and 47
      genotype studies were identified. Incidence and prevalence levels were high
      across all populations. Genotype 4 accounted for 94.1% of infections with a
      relative Shannon Diversity Index of only 14.4%. Pooled mean HCV prevalence was
      estimated at 11.9% (95% CI = 11.1-12.6%) among the general population, 55.6% (95%
      CI = 49.4-61.7%) among populations at high risk, 14.3% (95% CI = 10.3-18.8%)
      among populations at intermediate risk, 56.0% (95% CI = 50.4-61.6%) among
      populations with liver-related conditions, and 35.0% (95% CI = 27.3-43.1%) among
      special clinical populations. Mean HCV viremic rate was estimated at 66.7% (95%
      CI = 61.7-71.5%). Meta-regression indicated 6% lower odds for HCV prevalence for
      each one-year increment in publication year (AOR = 0.94; 95% CI = 0.92-0.96). HCV
      prevalence is high with evidence for ongoing transmission mainly through
      healthcare. Genotype diversity is low with genotype 4 dominance. Two-thirds of
      antibody-positive Egyptians are chronically infected and need treatment. Clinical
      populations should be prioritized for screening. Despite the large-scale
      epidemic, prevalence appears to be declining rapidly consistent with a
      contracting epidemic.

PMID- 29374181
TI  - Development and characterisation of a panel of phosphatidylinositide 3-kinase -
      mammalian target of rapamycin inhibitor resistant lung cancer cell lines.
AB  - The PI3K-mTOR pathway is involved in regulating all hallmarks of cancer, and is
      often dysregulated in NSCLC, making it an attractive therapeutic target in this
      setting. Acquired resistance to PI3K-mTOR inhibition is a major hurdle to
      overcome in the success of PI3K-mTOR targeted agents. H460, A549, and H1975
      resistant cells were generated by prolonged treatment in culture with Apitolisib
      (GDC-0980), a dual PI3K-mTOR inhibitor over a period of several months, from age
      matched parent cells. Resistance was deemed to have developed when a log fold
      difference in IC50 had been achieved. Resistant cell lines also exhibited
      resistance to another widely investigated PI3K-mTOR dual inhibitor; Dactolisib
      (BEZ235). Cell lines were characterised at the level of mRNA (expression array
      profiling expression of >150 genes), miRNA (expression array profiling of 2100
      miRNAs), protein (bottoms-up label-free mass spectrometry) and phosphoprotein
      (expression array profiling of 84 phospho/total proteins). Key alterations were
      validated by qPCR and Western blot. H1975 cells were initially most sensitive to
      Apitolisib (GDC-0980), but developed resistance more quickly than the other cell
      lines, perhaps due to increased selective pressure from the impressive initial
      effect. In-depth molecular profiling suggested epithelial-mesenchymal transition
      (EMT) may play a role in resistance to PI3K-mTOR dual inhibition in NSCLC.

PMID- 29374182
TI  - HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely
      Sampled Transmission Dynamics Analysis from 1986 to 2012.
AB  - Since HIV-1 treatment is increasingly considered an effective preventionstrategy,
      it is important to study local HIV-1 epidemics to formulate tailored
      preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until
      2005. To investigatethe shift in epidemiological trends, we studied the
      transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1
      transmission cohort that included 85 percent ofHIV-1-infected individuals linked
      to clinical care between 1986 and 2012 based on detailedclinical,
      epidemiological, behavioral and HIV-1 genetic information. Subtyping
      andtransmission cluster reconstruction were performed using maximum likelihood
      and Bayesianmethods, and the transmission chain network was linked to the
      clinical, epidemiological andbehavioral data. The results reveal that for the
      main HIV-1 subtype A1 and B sub-epidemics,young and drug-naive HIV-1-infected
      individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The
      results of this study provide a better understanding of thedynamics of the HIV-1
      infection in Cyprus, which may impact the development of preventionstrategies.
      Furthermore, this methodology for analyzing densely sampled transmissiondynamics
      is applicable to other geographic regions to implement effective HIV-1
      preventionstrategies in local settings.

PMID- 29374184
TI  - Creating a mouse model resistant to induced ischemic stroke and cardiovascular
      damage.
AB  - Vascular prostanoids, isomerized from an intermediate prostaglandin (PG), H2,
      produced by cyclooxygenase (COX), exert various effects on the vascular system,
      both protective and destructive. During endothelial dysfunction, vascular
      protector prostacyclin/prostaglandin I2 (PGI2) is decreased, while inflammatory
      PGE2 and thrombotic TXA2 are increased. Therefore, our research aim was to
      reverse the event by controlling PGH2 metabolism by generating an in vivo model
      via enzymatic engineering of COX-1 and prostacyclin synthase (PGIS). The COX-1
      and PGIS genes were linked to a 10-residue amino acid linker to form a Single
      chain Enzyme Complex (SCHEC), COX-1-10aa-PGIS. Transgenic (CP-Tg) mice in a FVB/N
      background were generated using the pronuclear microinjection method. We first
      confirmed mRNA and protein expression of COX-1-10aa-PGIS in various CP-Tg mouse
      tissues, as well as upregulation of circulating PGI2. We then examined the
      cardiovascular function of these mice. Our CP-Tg mice exhibited marked resistance
      to vascular assault through induced carotid arterial blockage, acute thrombotic
      stroke and arterial arrest, angiotensin-induced peripheral vasoconstriction, and
      hepatic lipid accumulation after receiving a high-fat diet. They also had a
      longer lifespan compared with wild-type mice. This study raises the possibility
      of fighting cardiovascular diseases by regulating cellular arachidonic acid
      derived PGH2 metabolites using enzymatic engineering.

PMID- 29374183
TI  - Structural insight into molecular mechanism of poly(ethylene terephthalate)
      degradation.
AB  - Plastics, including poly(ethylene terephthalate) (PET), possess many desirable
      characteristics and thus are widely used in daily life. However, non
      biodegradability, once thought to be an advantage offered by plastics, is causing
      major environmental problem. Recently, a PET-degrading bacterium, Ideonella
      sakaiensis, was identified and suggested for possible use in degradation and/or
      recycling of PET. However, the molecular mechanism of PET degradation is not
      known. Here we report the crystal structure of I. sakaiensis PETase (IsPETase) at
      1.5 A resolution. IsPETase has a Ser-His-Asp catalytic triad at its active site
      and contains an optimal substrate binding site to accommodate four
      monohydroxyethyl terephthalate (MHET) moieties of PET. Based on structural and
      site-directed mutagenesis experiments, the detailed process of PET degradation
      into MHET, terephthalic acid, and ethylene glycol is suggested. Moreover, other
      PETase candidates potentially having high PET-degrading activities are suggested
      based on phylogenetic tree analysis of 69 PETase-like proteins.

PMID- 29374185
TI  - Synergistic effect of a novel autophagy inhibitor and Quizartinib enhances cancer
      cell death.
AB  - Drug combinations have been increasingly applied in chemotherapy as a strategy to
      enhance the efficacy of anti-cancer treatment. The appropriate drug combinations
      may achieve synergistic effects beyond monotherapies alone. AC220 (Quizartinib),
      an FLT3 receptor tyrosine kinase inhibitor, developed for the treatment of AML,
      has been tested in phase II human clinical trials. However, AC220 as a
      monotherapy is not efficacious enough. In this study, we performed a small
      molecule screening of 12 640 compounds in order to find a compound that increase
      the AC220 efficacy in chemotherapy. We identified that TAK-165, a HER2 inhibitor,
      even when used at low nanomolar doses in combination with AC220, was able to
      induce cell death in different cancer cells, but not in non-cancer cell lines. We
      showed that TAK-165 and AC220 act synergistically to downregulate key signaling
      pathways and potently induce cancer cell death. Furthermore, we demonstrated that
      TAK-165 inhibited autophagy in a HER2-independent manner. Finally, we showed that
      the combination of TAK-165 and AC220 induced cell death in cancer cells through
      the activation of chaperone-mediated autophagy. Overall, these findings support
      the strategy for using AC220 and an autophagy inhibitor such as TAK-165 in a
      combinatorial treatment to enhance the efficacy of cancer therapies.

PMID- 29374186
TI  - Three-dimensional histochemistry and imaging of human gingiva.
AB  - In the present study, 3D histochemistry and imaging methodology is described for
      human gingiva to analyze its vascular network. Fifteen human gingiva samples
      without signs of inflammation were cleared using a mixture of 2-parts benzyl
      benzoate and 1-part benzyl alcohol (BABB), after being immunofluorescently
      stained for CD31, marker of endothelial cells to visualize blood vessels in
      combination with fluorescent DNA dyes. Samples were imaged in 3D with the use of
      confocal microscopy and light-sheet microscopy and image processing. BABB
      clearing caused limited tissue shrinkage 13 +/- 7% as surface area and 24 +/- 1%
      as volume. Fluorescence remained intact in BABB-cleared gingiva samples and light
      sheet microscopy was an excellent tool to image gingivae whereas confocal
      microscopy was not. Histochemistry on cryostat sections of gingiva samples after
      3D imaging validated structures visualized in 3D. Three-dimensional images showed
      the vascular network in the stroma of gingiva with one capillary loop in each
      stromal papilla invading into the epithelium. The capillary loops were tortuous
      with structural irregularities that were not apparent in 2D images. It is
      concluded that 3D histochemistry and imaging methodology described here is a
      promising novel approach to study structural aspects of human gingiva in health
      and disease.

PMID- 29374187
TI  - Downy mildew symptoms on grapevines can be reduced by volatile organic compounds
      of resistant genotypes.
AB  - Volatile organic compounds (VOCs) play a crucial role in the communication of
      plants with other organisms and are possible mediators of plant defence against
      phytopathogens. Although the role of non-volatile secondary metabolites has been
      largely characterised in resistant genotypes, the contribution of VOCs to
      grapevine defence mechanisms against downy mildew (caused by Plasmopara viticola)
      has not yet been investigated. In this study, more than 50 VOCs from grapevine
      leaves were annotated/identified by headspace-solid-phase microextraction gas
      chromatography-mass spectrometry analysis. Following P. viticola inoculation, the
      abundance of most of these VOCs was higher in resistant (BC4, Kober 5BB, SO4 and
      Solaris) than in susceptible (Pinot noir) genotypes. The post-inoculation
      mechanism included the accumulation of 2-ethylfuran, 2-phenylethanol, beta
      caryophyllene, beta-cyclocitral, beta-selinene and trans-2-pentenal, which all
      demonstrated inhibitory activities against downy mildew infections in water
      suspensions. Moreover, the development of downy mildew symptoms was reduced on
      leaf disks of susceptible grapevines exposed to air treated with 2-ethylfuran, 2
      phenylethanol, beta-cyclocitral or trans-2-pentenal, indicating the efficacy of
      these VOCs against P. viticola in receiver plant tissues. Our data suggest that
      VOCs contribute to the defence mechanisms of resistant grapevines and that they
      may inhibit the development of downy mildew symptoms on both emitting and
      receiving tissues.

PMID- 29374188
TI  - Impact of left atrial appendage morphology on thrombus formation after successful
      left atrial appendage occlusion: Assessment with cardiac-computed-tomography.
AB  - A standardized imaging algorithm by cardiac computed tomography angiography
      (cCTA) (LOVE-view) was used in 30 patients to evaluate the influence of different
      left atrial appendage (LAA) morphologies on development of thrombosis in the LAA
      6 months after implantation of an occlusion device (Watchman or Amplatzer-Cardiac
      Plug) in patients with non-valvular atrial fibrillation, CHA2DS2-VASc-Score >1
      and a contraindication for oral anticoagulation. The distribution of different
      LAA morphologies was 40% windsock, 17% broccoli and 43% chicken wing type. There
      was no significant difference in the level of thrombosis regarding LAA morphology
      or the type of chosen occlusion device. The rates of complete LAA thrombosis was
      40% in broccoli type, 33% in windsock and 15% in chicken wing type. Independently
      of LAA type, 13% had none and 60% incomplete thrombosis. The ratio of density
      (LA/LAA) was 0.14 in patients with complete thrombosis and 0.67 in those with
      none or incomplete thrombosis. cCTA and the LOVE-view-imaging-algorithm were
      shown to be a valuable method for standardized imaging in clinical routine in a
      greater set of patients. Surprisingly thrombosis of the occluded LAA was still in
      progress in most cases at 6 months, whereas further studies are needed defining
      its clinical consequences, especially for the selection of the optimal post
      procedural antithrombotic treatment strategy.

PMID- 29374189
TI  - Electronic Structure and Band Gap Engineering of Two-Dimensional Octagon
      Nitrogene.
AB  - A new phase of nitrogen with octagon structure has been predicted in our previous
      study, which we referred to as octagon-nitrogene (ON). In this work, we make
      further investigations of its stability and electronic structures. The phonon
      dispersion has no imaginary phonon modes, which indicates that ON is dynamically
      stable. Using ab initio molecular dynamic simulations, this structure is found to
      be stable up to room temperature and possibly higher, and ripples that are
      similar to that of graphene are formed on the ON sheet. Based on the density
      functional theory calculation, we find that single layer ON is a two-dimension
      wide gap semiconductor with an indirect band gap of 4.7 eV. This gap can be
      decreased by stacking due to the interlayer interactions. Biaxial tensile strain
      and perpendicular electric field can greatly influence the band structure of ON,
      in which the gap decreases and eventually closes as the biaxial tensile strain or
      the perpendicular electric field increases. In other words, both biaxial tensile
      strain and a perpendicular electric field can drive the insulator-to-metal
      transition, and thus can be used to engineer the band gap of ON. From our
      results, we see that ON has potential applications in many fields, including
      electronics, semiconductors, optics and spintronics.

PMID- 29374190
TI  - Real-Time Characterization Using in situ RHEED Transmission Mode and TEM for
      Investigation of the Growth Behaviour of Nanomaterials.
AB  - A novel characterization technique using both in situ reflection high-energy
      electron diffraction (RHEED) transmission mode and transmission electron
      microscopy (TEM) has been developed to investigate the growth behaviour of
      semiconductor nanostructures. RHEED employed in transmission mode enables the
      acquisition of structural information during the growth of nanostructures such as
      nanorods. Such real-time observation allows the investigation of growth
      mechanisms of various nanomaterials that is not possible with conventional ex
      situ analytical methods. Additionally, real-time monitoring by RHEED transmission
      mode offers a complete range of information when coupled with TEM, providing
      structural and chemical information with excellent spatial resolution, leading to
      a better understanding of the growth behaviour of nanomaterials. Here, as a
      representative study using the combined technique, the nucleation and
      crystallization of InAs nanorods and the epitaxial growth of InxGa1-xAs(GaAs)
      shell layers on InAs nanorods are explored. The structural changes in the InAs
      nanorods at the early growth stage caused by the transition of the local growth
      conditions and the strain relaxation processes that occur during epitaxial
      coating of the shell layers are shown. This technique advances our understanding
      of the growth behaviour of various nanomaterials, which allows the realization of
      nanostructures with novel properties and their application in future electronics
      and optoelectronics.

PMID- 29374191
TI  - High-resolution seismic event detection using local similarity for Large-N
      arrays.
AB  - We develop a novel method for seismic event detection that can be applied to
      large-N arrays. The method is based on a new detection function named local
      similarity, which quantifies the signal consistency between the examined station
      and its nearest neighbors. Using the 5200-station Long Beach nodal array, we
      demonstrate that stacked local similarity functions can be used to detect seismic
      events with amplitudes near or below noise levels. We apply the method to one
      week continuous data around the 03/11/2011 Mw 9.1 Tohoku-Oki earthquake, to
      detect local and distant events. In the 5-10 Hz range, we detect various events
      of natural and anthropogenic origins, but without a clear increase in local
      seismicity during and following the surface waves of the Tohoku-Oki mainshock. In
      the 1-Hz low-pass-filtered range, we detect numerous events, likely representing
      aftershocks from the Tohoku-Oki mainshock region. This high-resolution detection
      technique can be applied to both ultra-dense and regular array recordings for
      monitoring ultra-weak micro-seismicity and detecting unusual seismic events in
      noisy environments.

PMID- 29374193
TI  - A new bound on polymer quantization via an opto-mechanical setup.
AB  - The existence of a minimal measurable length as a characteristic length in the
      Planck scale is one of the main features of quantum gravity and has been widely
      explored in the context. Various different deformations of spacetime have been
      employed successfully for the purpose. However, polymer quantization approach is
      a relatively new and dynamic field towards the quantum gravity phenomenology,
      which emerges from the symmetric sector of the loop quantum gravity. In this
      article, we extend the standard ideas of polymer quantization to find a new and
      tighter bound on the polymer deformation parameter. Our protocol relies on an
      opto-mechanical experimental setup that was originally proposed to explore some
      interesting phenomena by embedding the minimal length into the standard canonical
      commutation relation. We extend this scheme to probe the polymer length deformed
      canonical commutation relation of the center of mass mode of a mechanical
      oscillator with a mass around the Planck scale. The method utilizes the novelty
      of exchanging the relevant mechanical information with a high intensity optical
      pulse inside an optical cavity. We also demonstrate that our proposal is within
      the reach of the current technologies and, thus, it could uncover a decent
      realization of quantum gravitational phenomena thorough a simple table-top
      experiment.

PMID- 29374192
TI  - Novel mechanisms of Collagenase Santyl Ointment (CSO) in wound macrophage
      polarization and resolution of wound inflammation.
AB  - Collagenases are useful in enzymatic wound debridement. Clostridial collagenase,
      marketed as Collagenase Santyl Ointment (CSO), is FDA approved for such use.
      Building on the scientific premise that collagenases as well as collagen
      degradation products may regulate immune cell function, we sought to investigate
      the potential role of CSO in wound inflammation. We tested the hypothesis that in
      addition to enacting debridement, CSO contributes to the resolution of persistent
      wound inflammation. Wound macrophages were isolated from PVA sponges loaded with
      CSO or petrolatum and implanted in mice. Significant increase in pro-reparative
      and decrease in pro-inflammatory polarization was noted in macrophages of acute
      as well as diabetic wounds. Wound macrophages from CSO-treated group displayed
      increased production of anti-inflammatory cytokines IL-10 and TGF-beta, and
      decreased levels of pro-inflammatory cytokines TNF-alpha and IL-1beta. The active
      ingredient of CSO, CS-API, induced the expression of mphiheal /M(IL-4)
      polarization markers ex vivo. CS-API treatment attenuated transactivation of NF
      kappaB and significantly induced STAT6 phosphorylation. A significant role of a
      novel PGE2-EP4 pathway in CS-API induced STAT6 activation and the mphiheal /M(IL
      4) polarization was identified. Taken together, findings of this work reposition
      CSO as a potential agent that may be effective in resolving wound inflammation,
      including diabetic wounds.

PMID- 29374194
TI  - 2-Phenylquinazolinones as dual-activity tankyrase-kinase inhibitors.
AB  - Tankyrases (TNKSs) are enzymes specialized in catalyzing poly-ADP-ribosylation of
      target proteins. Several studies have validated TNKSs as anti-cancer drug targets
      due to their regulatory role in Wnt/beta-catenin pathway. Recently a lot of
      effort has been put into developing more potent and selective TNKS inhibitors and
      optimizing them towards anti-cancer agents. We noticed that some 2
      phenylquinazolinones (2-PQs) reported as CDK9 inhibitors were similar to
      previously published TNKS inhibitors. In this study, we profiled this series of 2
      PQs against TNKS and selected kinases that are involved in the Wnt/beta-catenin
      pathway. We found that they were much more potent TNKS inhibitors than they were
      CDK9/kinase inhibitors. We evaluated the compound selectivity to tankyrases over
      the ARTD enzyme family and solved co-crystal structures of the compounds with
      TNKS2. Comparative structure-based studies of the catalytic domain of TNKS2 with
      selected CDK9 inhibitors and docking studies of the inhibitors with two kinases
      (CDK9 and Akt) revealed important structural features, which could explain the
      selectivity of the compounds towards either tankyrases or kinases. We also
      discovered a compound, which was able to inhibit tankyrases, CDK9 and Akt kinases
      with equal uM potency.

PMID- 29374195
TI  - Restrained management of copper level enhances the antineoplastic activity of
      imatinib in vitro and in vivo.
AB  - The present study was designed to investigate if elevated copper level can be
      targeted to enhance the efficacy of a significant anticancer drug, imatinib
      (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK
      293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common
      drug target. The cell lines were treated with the different doses of copper
      chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with
      the drug for 24 h in standard culture medium and conditions. The treated cells
      were subjected to various assays including MTT, PARP, p-53, caspase-7, caspase-3,
      LDH and single cell electrophoresis. The study shows that DSF and Cu (II)
      synergizes the anticancer activity of ITB to a significant extent in a dose
      specific way as evidenced by the combinations treated groups. Furthermore, the
      same treatment strategy was employed in cancer-induced rats in which the
      combinations of ITB-DSF and ITB-Cu II showed enhanced antineoplastic activity as
      compared to ITB alone. However, DSF was more effective than Cu (II) as an
      adjuvant to the drug. Hence, restrained manipulation of copper level in tumor
      cells can orchestrate the redox and molecular dispositions inside the cells
      favoring the induction of apoptosis.

PMID- 29374196
TI  - Predicting non-melanoma skin cancer via a multi-parameterized artificial neural
      network.
AB  - Ultraviolet radiation (UVR) exposure and family history are major associated risk
      factors for the development of non-melanoma skin cancer (NMSC). The objective of
      this study was to develop and validate a multi-parameterized artificial neural
      network based on available personal health information for early detection of
      NMSC with high sensitivity and specificity, even in the absence of known UVR
      exposure and family history. The 1997-2015 NHIS adult survey data used to train
      and validate our neural network (NN) comprised of 2,056 NMSC and 460,574 non
      cancer cases. We extracted 13 parameters for our NN: gender, age, BMI, diabetic
      status, smoking status, emphysema, asthma, race, Hispanic ethnicity,
      hypertension, heart diseases, vigorous exercise habits, and history of stroke.
      This study yielded an area under the ROC curve of 0.81 and 0.81 for training and
      validation, respectively. Our results (training sensitivity 88.5% and specificity
      62.2%, validation sensitivity 86.2% and specificity 62.7%) were comparable to a
      previous study of basal and squamous cell carcinoma prediction that also included
      UVR exposure and family history information. These results indicate that our NN
      is robust enough to make predictions, suggesting that we have identified novel
      associations and potential predictive parameters of NMSC.

PMID- 29374197
TI  - A comparative study of fruit and vegetable consumption and physical activity
      among adolescents in 49 Low-and-Middle-Income Countries.
AB  - Physical inactivity and low consumption of fruits and vegetables (FV) during
      adolescence may persist through adulthood, putting adolescents at risk of
      developing chronic diseases. Although studies from high-income countries have
      reported differences in FV consumption and physical activity (PA) between
      adolescent boys and girls, few exist from low-and-middle-income countries
      (LMICs). In this study, we examined patterns of FV consumption and PA among
      adolescent boys and girls in LMICs. Country selection was based on availability
      of Global School-Based Student Health Survey (GSHS) data from 2004 to 2013. The
      total analytic sample was 164,771 adolescents from 49 LMICs. Descriptive
      statistics were generated to determine adolescents meeting the World Health
      Organization (WHO) recommendations for FV and PA. A Rao-Scott adjusted chi-square
      statistic was computed to assess gender differences. Less than 30% of adolescents
      across all countries met the WHO guidelines for FV consumption or PA. Morocco
      (29.5%) and India (29.5%) however had the highest percentage of adolescents
      meeting recommendations for FV and PA, respectively. Adolescent boys were more
      active than girls, and this difference was more notable in the Middle East and
      North African region. Adolescents achieving the WHO recommendations for daily
      consumption of FV and PA were consistently low in all countries.

PMID- 29374198
TI  - Color and time perception: Evidence for temporal overestimation of blue stimuli.
AB  - The perceived duration of a visual stimulus depends on various features, such as
      its size, shape, and movement. Potential effects of stimulus color have not been
      investigated in sufficient detail yet, but the well-known effects of arousal on
      time perception suggest that arousing hues, such as red, might induce an
      overestimation of duration. By means of a two-interval duration discrimination
      task in the sub-second range, we investigated whether participants overestimate
      the duration of red stimuli in comparison to blue stimuli, while controlling for
      differences in brightness (individual adjustments by means of flicker photometry)
      and saturation (colorimetric adjustment in terms of the CIELAB color space).
      Surprisingly, our results show an overestimation of the duration of blue compared
      to red stimuli (indicated by a shift of the point of subjective equality), even
      though the red stimuli were rated as being more arousing. The precision
      (variability) of duration judgments, i.e., the duration difference limen, did not
      differ between red and blue stimuli, questioning an explanation in terms of
      attentional processes.

PMID- 29374199
TI  - AmPEP: Sequence-based prediction of antimicrobial peptides using distribution
      patterns of amino acid properties and random forest.
AB  - Antimicrobial peptides (AMPs) are promising candidates in the fight against
      multidrug-resistant pathogens owing to AMPs' broad range of activities and low
      toxicity. Nonetheless, identification of AMPs through wet-lab experiments is
      still expensive and time consuming. Here, we propose an accurate computational
      method for AMP prediction by the random forest algorithm. The prediction model is
      based on the distribution patterns of amino acid properties along the sequence.
      Using our collection of large and diverse sets of AMP and non-AMP data (3268 and
      166791 sequences, respectively), we evaluated 19 random forest classifiers with
      different positive:negative data ratios by 10-fold cross-validation. Our optimal
      model, AmPEP with the 1:3 data ratio, showed high accuracy (96%), Matthew's
      correlation coefficient (MCC) of 0.9, area under the receiver operating
      characteristic curve (AUC-ROC) of 0.99, and the Kappa statistic of 0.9.
      Descriptor analysis of AMP/non-AMP distributions by means of Pearson correlation
      coefficients revealed that reduced feature sets (from a full-featured set of 105
      to a minimal-feature set of 23) can result in comparable performance in all
      respects except for some reductions in precision. Furthermore, AmPEP outperformed
      existing methods in terms of accuracy, MCC, and AUC-ROC when tested on benchmark
      datasets.

PMID- 29374200
TI  - Interplay between TETs and microRNAs in the adult brain for memory formation.
AB  - 5-hydroxymethylation (5-hmC) is an epigenetic modification on DNA that results
      from the conversion of 5-methylcytosine by Ten-Eleven Translocation (TET)
      proteins. 5-hmC is widely present in the brain and is subjected to dynamic
      regulation during development and upon neuronal activity. It was recently shown
      to be involved in memory processes but currently, little is known about how it is
      controlled in the brain during memory formation. Here, we show that Tet3 is
      selectively up-regulated by activity in hippocampal neurons in vitro, and after
      formation of fear memory in the hippocampus. This is accompanied by a decrease in
      miR-29b expression that, through complementary sequences, regulates the level of
      Tet3 by preferential binding to its 3'UTR. We newly reveal that SAM68, a nuclear
      RNA-binding protein known to regulate splicing, acts upstream of miR-29 by
      modulating its biogenesis. Together, these findings identify novel players in the
      adult brain necessary for the regulation of 5-hmC during memory formation.

PMID- 29374202
TI  - Chirality recognition of winding vine-shaped heterobiaryls with molecular
      asymmetry. Kinetic and dynamic kinetic resolution by Shi's asymmetric
      epoxidation.
AB  - The chirality of winding vine-shaped heterobiaryls with molecular asymmetry is
      recognized by a sugar-based chiral oxidant. Kinetic resolution of (+/-)
      bisbenzoimidazole bearing an olefin moiety takes place with Shi's asymmetric
      epoxidation to observe krel value up to ca. 35 affording the corresponding
      epoxide. The reaction of a (+/-)-bithiophene derivative also recognized the
      chirality to give the corresponding epoxide with er of 96:4 at 39% conversion.
      Dynamic kinetic resolution is found to take place when unsymmetrical biaryl
      composed of benzoimidazole/thiophene is subjected to Shi's epoxidation, whose
      conversion of the racemic substrate exceeds to 50%.

PMID- 29374201
TI  - C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs
      from complement factor H: implications for retinal inflammation.
AB  - Retinal inflammation plays a key role in the progression of age-related macular
      degeneration (AMD), a condition that leads to loss of central vision. The
      deposition of the acute phase pentraxin C-reactive protein (CRP) in the macula
      activates the complement system, thereby contributing to dysregulated
      inflammation. The complement protein factor H (FH) can bind CRP and down-regulate
      an inflammatory response. However, it is not known whether a truncated form of
      FH, called factor H-like protein 1 (FHL-1), which plays a significant regulatory
      role in the eye, also interacts with CRP. Here, we compare the binding properties
      of FHL-1 and FH to both CRP and the related protein pentraxin-3 (PTX3). We find
      that, unlike FH, FHL-1 can bind pro-inflammatory monomeric CRP (mCRP) as well as
      the circulating pentameric form. Furthermore, the four-amino acid C-terminal tail
      of FHL-1 (not present in FH) plays a role in mediating its binding to mCRP. PTX3
      was found to be present in the macula of donor eyes and the AMD-associated Y402H
      polymorphism altered the binding of FHL-1 to PTX3. Our findings reveal that the
      binding characteristics of FHL-1 differ from those of FH, likely underpinning
      independent immune regulatory functions in the context of the human retina.

PMID- 29374203
TI  - Effect of secondary phase on the electromagnetic shielding effectiveness of
      magnesium alloy.
AB  - The microstructure, electrical conductivity, and electromagnetic interference
      (EMI) shielding effectiveness (SE) of Mg-xZn and Mg-xSn (x = 3,5) alloys prepared
      under different rolling and heat treatment conditions were systematically
      investigated to understand the effect of secondary-phase orientation on the
      electromagnetic-shielding property of magnesium alloys. Alloys were rolled to
      form basal textures and then subjected to different durations of solid-solution
      treatment and aging to induce the precipitation of secondary-phase particles
      along a specific direction. Experimental results indicated that in Mg-Zn and Mg
      Sn alloys, secondary phases precipitated along directions perpendicular and
      parallel to the basal plane, respectively. When the direction of the incident
      electromagnetic wave is perpendicular to the basal plane, precipitates in Mg-Sn
      alloy parallel to the basal plane improve SE. The increment in SE is mainly
      attributed to the improvement in the reflection and multiple reflection losses of
      incident electromagnetic waves, which are caused by increasing the amounts of
      precipitates with specific orientations. Mg-5Sn alloy subjected to 16 h of
      solution treatment at 480  degrees C and 60 h of artificial aging at 170  degrees
      C for 60 h exhibited the maximum value of 107-89 dB and maximum increment in SE
      of 13 dB at 1200 MHz.

PMID- 29374204
TI  - A retrospective clinical comparison of daptomycin vs daptomycin and a beta-lactam
      antibiotic for treating vancomycin-resistant Enterococcus faecium bloodstream
      infections.
AB  - There is limited clinical evidence to support the combination of daptomycin and
      beta-lactam antibiotics (DAP + BLA) for treatment of vancomycin-resistant
      enterococci (VRE) bloodstream infections (BSI). We conducted a prospective
      observational cohort study of VRE-BSI during 2010-2015. The primary endpoint was
      mortality at the end of treatment. We included 114 patients who received DAP for
      VRE-BSI. Of these 87 (76.3%) received DAP + BLA. There were no significant
      differences in mortality between the DAP and DAP + BLA groups on univariable
      analysis (10/27 vs. 34/87, P = 0.85). A subgroup analysis of patients with
      enterococcal DAP minimum inhibitory concentrations (MICs) <=2 mg/L, revealed that
      those treated with DAP + BLA had a lower mortality (adjusted hazard ratio [aHR],
      0.23; 95% confidence interval [CI], 0.06-0.93; P = 0.04) after adjustment for
      other significant predictors of mortality, including the DAP dose. In addition,
      patients receiving high-dose (>=9 mg/kg) DAP + BLA independently had a better
      survival than those receiving low-dose DAP alone (aHR = 5.16), low-dose DAP + BLA
      (aHR = 5.39), and high-dose DAP alone (aHR = 19.01) (P < 0.05 for all
      comparisons). For patients with VRE-BSIs, the DAP MIC of the isolate and the DAP
      dose influence the effect of DAP + BLA on outcome. A high-dose DAP + BLA might
      improve survival. These findings support the use of high-dose DAP + BLA for
      treatment of VRE-BSI.

PMID- 29374205
TI  - Vibrio cholerae embraces two major evolutionary traits as revealed by targeted
      gene sequencing.
AB  - Vibrio cholerae inhabits aquatic environments worldwide and has over 200
      recognized serogroups classified by O-polysaccharide specificity. Here, we report
      that V. cholerae selects either of two genetic traits during their evolution.
      Sequencing of the specific gene locus MS6_A0927 revealed that 339 of 341 strains
      of V. cholerae and closely related Vibrio species originating from 34 countries
      over a century carried either metY (M) (~1,269 bp) or luxR-hchA (LH) (~1,600 bp)
      genes, and consequently those vibrios were separated into two clusters, M (45.4%)
      and LH (54.6%). Only two strains contained both M and LH in the same locus.
      Moreover, extensive polymorphisms in those genes were detected in M and LH with
      79 and 46 sequence variations, respectively. V. cholerae O1 strains isolated from
      cholera outbreaks worldwide, and some non-O1 strains evolving from O1 via
      exchange of genes encoding cell surface polysaccharides possessed LH alleles.
      Analysis of polymorphisms in the gene locus implicated a high degree of genetic
      diversity and identical subpopulations among the V. cholerae species.

PMID- 29374206
TI  - Transcriptomic characterization and potential marker development of contrasting
      sugarcane cultivars.
AB  - Sugarcane (Saccharum officinarum L.) is an important crop for sugar production
      and bioenergy worldwide. In this study, we performed transcriptome sequencing for
      six contrasting sugarcane genotypes involved in leaf abscission, tolerance to
      pokkah boeng disease and drought stress. More than 465 million high-quality reads
      were generated, which were de novo assembled into 93,115 unigenes. Based on a
      similarity search, 43,526 (46.74%) unigenes were annotated against at least one
      of the public databases. Functional classification analyses showed that these
      unigenes are involved in a wide range of metabolic pathways. Comparative
      transcriptome analysis revealed that many unigenes involved in response to
      abscisic acid and ethylene were up-regulated in the easy leaf abscission
      genotype, and unigenes associated with response to jasmonic acid and salicylic
      acid were up-regulated in response to the pokkah boeng disease in the tolerance
      genotype. Moreover, unigenes related to peroxidase, antioxidant activity and
      signal transduction were up-regulated in response to drought stress in the
      tolerant genotype. Finally, we identified a number of putative markers, including
      8,630 simple sequence repeats (SSRs) and 442,152 single-nucleotide polymorphisms
      (SNPs). Our data will be important resources for future gene discovery, molecular
      marker development, and genome studies in sugarcane.

PMID- 29374207
TI  - Variability in phase and amplitude of diurnal rhythms is related to variation of
      mood in bipolar and borderline personality disorder.
AB  - Variable mood is an important feature of psychiatric disorders. However, its
      measurement and relationship to objective measureas of physiology and behaviour
      have rarely been studied. Smart-phones facilitate continuous personalized
      prospective monitoring of subjective experience and behavioural and physiological
      signals can be measured through wearable devices. Such passive data streams allow
      novel estimates of diurnal variability. Phase and amplitude of diurnal rhythms
      were quantified using new techniques that fitted sinusoids to heart rate (HR) and
      acceleration signals. We investigated mood and diurnal variation for four days in
      20 outpatients with bipolar disorder (BD), 14 with borderline personality
      disorder (BPD) and 20 healthy controls (HC) using a smart-phone app, portable
      electrocardiogram (ECG), and actigraphy. Variability in negative affect, positive
      affect, and irritability was elevated in patient groups compared with HC. The
      study demonstrated convincing associations between variability in subjective mood
      and objective variability in diurnal physiology. For BPD there was a pattern of
      positive correlations between mood variability and variation in activity, sleep
      and HR. The findings suggest BPD is linked more than currently believed with a
      disorder of diurnal rhythm; in both BPD and BD reducing the variability of sleep
      phase may be a way to reduce variability of subjective mood.

PMID- 29374208
TI  - Down-regulation of guanylate binding protein 1 causes mitochondrial dysfunction
      and cellular senescence in macrophages.
AB  - Macrophage polarization is tightly associated with its metabolic reprograming and
      immune dysfunction. However, the intracellular molecules/pathways that connect
      these alterations in inflammatory macrophages remain largely unidentified.
      Herein, we explored the role of guanylate binding protein 1 (Gbp1), an
      intracellular anti-microbial protein, in regulating polarization, metabolic
      reprogramming, and cellular aging of macrophages. We showed that Gbp1 expression
      in inguinal white adipose tissue is significantly decreased in high-fat diet -fed
      and aged mice. Gbp1 expression is significantly induced by IFNgamma and LPS in
      macrophages but not adipocytes. Downregulation of Gbp1 expression causes
      macrophage polarization towards a pro-inflammatory phenotype. Gbp1 knockdown (Kd)
      macrophages have impaired mitochondrial respiratory function, which is further
      supported by down-regulation of genes encoding electron transport chain
      components and genes involved in fatty acid oxidation and mitochondrial function.
      Moreover, we observed Gbp1 is localized in both cytosol and mitochondrial
      fraction, and Gbp1 Kd macrophages display decreased mitophagy activity. More
      interestingly, Gbp1 Kd macrophages undergo senescence as evidenced by increased
      activation of AMPK-p53 pathway and positive staining of beta-galactosidase. These
      observations suggest that Gbp1 may play an important role in protecting against
      mitochondrial dysfunction and preserving immune function of macrophages during
      inflammatory stress and aging.

PMID- 29374209
TI  - Mitonuclear interactions may contribute to fitness of fungal hybrids.
AB  - Hybridization between species is being recognized as a major force in the rapid
      adaptive evolution of fungal plant pathogens. The first stages of interspecific
      hybridization necessarily involve nuclear-mitochondrial chimeras. In their 2001
      publication, Olson and Stenlid reported that mitochondria control the virulence
      of first generation hybrids between the North American fungal pathogen
      Heterobasidion irregulare and its congeneric H. occidentale. By assessing
      saprobic ability and gene expression of H. irregulare * H. annosum sensu stricto
      hybrids and of their parental genotypes, we demonstrate that mitochondria also
      influence saprobic growth of hybrids. Moreover, gene expression data suggest that
      fungal fitness is modulated by an intimate interplay between nuclear genes and
      mitochondrial type, and is dependent on the specific mitonuclear combination.

PMID- 29374210
TI  - Characterization of Conformational Ensembles of Protonated N-glycans in the Gas
      Phase.
AB  - Ion mobility mass spectrometry (IM-MS) is a technique capable of investigating
      structural changes of biomolecules based on their collision cross section (CCS).
      Recent advances in IM-MS allow us to separate carbohydrate isomers with subtle
      conformational differences, but the relationship between CCS and atomic structure
      remains elusive. Here, we characterize conformational ensembles of gas-phase N
      glycans under the electrospray ionization condition using molecular dynamics
      simulations with enhanced sampling. We show that the separation of CCSs between
      isomers reflects folding features of N-glycans, which are determined both by
      chemical compositions and protonation states. Providing a physicochemical basis
      of CCS for N-glycans helps not only to interpret IM-MS measurements but also to
      estimate CCSs of complex glycans.

PMID- 29374211
TI  - Low Altitude Solar Magnetic Reconnection, Type III Solar Radio Bursts, and X-ray
      Emissions.
AB  - Type III solar radio bursts are the Sun's most intense and frequent nonthermal
      radio emissions. They involve two critical problems in astrophysics, plasma
      physics, and space physics: how collective processes produce nonthermal radiation
      and how magnetic reconnection occurs and changes magnetic energy into kinetic
      energy. Here magnetic reconnection events are identified definitively in Solar
      Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets,
      current sheets, and cusp-like geometries on top of time-varying magnetic loops,
      and strong outflows along pairs of open magnetic field lines. Type III bursts
      imaged by the Murchison Widefield Array and detected by the Learmonth
      radiospectrograph and STEREO B spacecraft are demonstrated to be in very good
      temporal and spatial coincidence with specific reconnection events and with
      bursts of X-rays detected by the RHESSI spacecraft. The reconnection sites are
      low, near heights of 5-10 Mm. These images and event timings provide the long
      desired direct evidence that semi-relativistic electrons energized in magnetic
      reconnection regions produce type III radio bursts. Not all the observed
      reconnection events produce X-ray events or coronal or interplanetary type III
      bursts; thus different special conditions exist for electrons leaving
      reconnection regions to produce observable radio, EUV, UV, and X-ray bursts.

PMID- 29374212
TI  - Tissue Factor-bearing MPs and the risk of venous thrombosis in cancer patients: A
      meta-analysis.
AB  - Cancer patients with Tissue Factor (TF)-bearing MPs have been presented
      association with increased risk of venous thromboembolism (VTE), but results of
      these studies have not been consistent. We aimed to conduct a meta-analysis to
      assess the relationship between TF-bearing MPs and risk of VTE in patients with
      cancer. PubMed, Web of Science and EMBASE Databases were systematically retrieved
      up to1th June 2017. Two case-control studies and four cohort studies met the
      entry requirements in this analysis. The summary odd ratio (OR) were estimated by
      a random effect model. The overall OR was 1.76 (95% CI: 1.21-2.56, I2 = 62.0%).
      The OR of case-control studies was 3.41 (95% CI: 1.45-8.02, I2 = 0.0%) and that
      of cohort studies was1.53 (95% CI: 1.05-2.24, I2 = 66.1%). The association
      between TF-bearing MPs and the risk of VTE in cancer patients was found in this
      meta-analysis. Publication bias testing and sensitivity subgroup analysis
      suggested that results of this meta-analysis were robustness. In conclusion, TF
      bearing MPs were associated with increased risk of VTE in patients with cancer.
      Whereas, more well-designed studies and more comprehensive adjustments for
      confounders in further studies are warranted to affirm the association.

PMID- 29374213
TI  - Cerebrospinal fluid chemokine patterns in children with enterovirus 71-related
      encephalitis.
AB  - Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth
      disease (HFMD) as well as neurological complications, such as encephalitis. The
      chemokines involved in the migration of leukocytes have increasingly been
      implicated in infectious diseases of the central nervous system. Few studies have
      evaluated the levels of chemokines in HMFD children with EV71-related
      encephalitis. In the present study, we evaluated the cerebrospinal fluid (CSF)
      levels of the chemokines IL-8, RANTES, MIG, MCP-1 and IP-10 in 99 children with
      EV71-related encephalitis and 22 children with febrile convulsion (FC). We found
      that the concentrations of IL-8, RANTES, MIG and IP-10 were significantly higher
      in HFMD children with encephalitis compared to patients with FC. Additionally,
      these four chemokines were dramatically reduced during convalescence. Inversely,
      the level of MCP-1 was lower in encephalitis patients than FC patients and was
      not significantly reduced during convalescence. Additionally, MIG was strongly
      correlated with IP-10 in encephalitis patients. Furthermore, the area under the
      ROC curve (AUC) of CSF MIG and IP-10 in distinguishing encephalitis from FC were
      0.869 and 0.876, and the corresponding sensitivities/specificities were
      67.7%/100.0% and 67.7%/95.5%, respectively. In conclusion, our results indicate
      that chemokines play important roles in the pathogenesis of EV71 infection.

PMID- 29374214
TI  - Phylogenomic reclassification of the world's most venomous spiders
      (Mygalomorphae, Atracinae), with implications for venom evolution.
AB  - Here we show that the most venomous spiders in the world are phylogenetically
      misplaced. Australian atracine spiders (family Hexathelidae), including the
      notorious Sydney funnel-web spider Atrax robustus, produce venom peptides that
      can kill people. Intriguingly, eastern Australian mouse spiders (family
      Actinopodidae) are also medically dangerous, possessing venom peptides strikingly
      similar to Atrax hexatoxins. Based on the standing morphology-based
      classification, mouse spiders are hypothesized distant relatives of atracines,
      having diverged over 200 million years ago. Using sequence-capture phylogenomics,
      we instead show convincingly that hexathelids are non-monophyletic, and that
      atracines are sister to actinopodids. Three new mygalomorph lineages are elevated
      to the family level, and a revised circumscription of Hexathelidae is presented.
      Re-writing this phylogenetic story has major implications for how we study venom
      evolution in these spiders, and potentially genuine consequences for antivenom
      development and bite treatment research. More generally, our research provides a
      textbook example of the applied importance of modern phylogenomic research.

PMID- 29374215
TI  - Geophysical investigations unravel the vestiges of ancient meandering channels
      and their dynamics in tidal landscapes.
AB  - Whether or not one can detect relict signatures of the past imprinted in current
      landscapes is a question of the utmost theoretical and practical relevance for
      meandering tidal channels, owing to their influence on the morphodynamic
      evolution of tidal landscapes, a critically fragile environment, especially in
      face of expected climatic changes. Unravelling the sedimentary patterns of
      ancient channels is an expensive process that usually requires high resolution
      sediment coring. Here we use a novel inversion process of multi-frequency
      electromagnetic measurements to reveal the signature and characterize the
      dynamics of a salt-marsh paleo-meander in the Venice Lagoon. We show that the
      ancient meander migrated laterally while vertically aggrading, developing a
      peculiar bar geometry which is less common in analogous fluvial meanders. The
      observed point-bar dynamics and the associated architectural geometry are
      consistent with remote sensing and borehole data and contrast with current
      assessments of tidal meander morphodynamics mediated from classical fluvial
      theories. In addition, the proposed technique, rapid and non-invasive, bears
      important consequences for detecting buried stratal geometries and reconstructing
      the spatial distribution of ancient sedimentary bodies, providing quantitative
      data for the description of landscape evolution in time.

PMID- 29374216
TI  - Warning signals of biodiversity collapse across gradients of tropical forest
      loss.
AB  - We evaluate potential warning signals that may aid in identifying the proximity
      of ecological communities to biodiversity thresholds from habitat loss-often
      termed "tipping points"-in tropical forests. We used datasets from studies of
      Neotropical mammal, frog, bird, and insect communities. Our findings provide only
      limited evidence that an increase in the variance (heteroskedasticity) of
      biodiversity-related parameters can provide a general warning signal of impending
      threshold changes in communities, as forest loss increases. However, such an
      apparent effect was evident for amphibians in the Brazilian Atlantic Forest and
      Amazonian mammal and bird communities, suggesting that impending changes in some
      species assemblages might be predictable. We consider the potential of such
      warning signs to help forecast drastic changes in biodiversity.

PMID- 29374217
TI  - Increased Exposure of Tacrolimus by Co-administered Mycophenolate Mofetil:
      Population Pharmacokinetic Analysis in Healthy Volunteers.
AB  - The objective of the study was to investigate the pharmacokinetic drug-drug
      interactions between tacrolimus (TAC) and mycophenolate mofetil (MMF) in healthy
      Korean male volunteers. Seventeen volunteers participated in a three-period,
      single-dose, and fixed sequence study. They sequentially received MMF, TAC, and
      the combination. Concentrations of TAC, mycophenolic acid (MPA), and its
      metabolites MPA 7-O-glucuronide and MPA acyl glucuronide were measured. The
      variants of CYP3A4, CYP3A5, SLCO1B1, SLCO1B3, ABCC2, UGT1A9, and UGT2B7 were
      genotyped. Drug interaction was evaluated with a non-compartmental analysis and
      population pharmacokinetic modelling to quantify the interaction effect. A total
      of 1,082 concentrations of those analytes were analysed. AUC0-inf of TAC
      increased by 22.1% (322.4 +/- 174.1 to 393.6 +/- 121.7 ng.h/mL; P < 0.05) when co
      administered with MMF, whereas the pharmacokinetic parameters of MPA and its
      metabolites were not changed by TAC. Apparent clearance (CL/F) of TAC was 17.8
      L/h [relative standard error (RSE) 11%] or 13.8 L/h (RSE 11%) without or with
      MMF, respectively. Interaction was explained by the exponential model. The CYP3A5
      genotype was the only significant covariate. The population estimate of CL/F of
      TAC was 1.48-fold (RSE 16%) in CYP3A5 expressers when compared to nonexpressers.
      CL/F of TAC was decreased when co-administered with MMF in these subjects.

PMID- 29374218
TI  - Different milk diets have substantial effects on the jejunal mucosal immune
      system of pre-weaning calves, as demonstrated by whole transcriptome sequencing.
AB  - There is increasing evidence that nutrition during early mammalian life has a
      strong influence on health and performance in later life. However, there are
      conflicting data concerning the appropriate milk diet. This discrepancy
      particularly applies to ruminants, a group of mammals that switch from
      monogastric status to rumination during weaning. Little is known regarding how
      the whole genome expression pattern in the juvenile ruminant gut is affected by
      alternative milk diets. Thus, we performed a next-generation-sequencing-based
      holistic whole transcriptome analysis of the jejunum in male pre-weaned German
      Holstein calves fed diets with restricted or unlimited access to milk during the
      first 8 weeks of life. Both groups were provided hay and concentrate ad libitum.
      The analysis of jejunal mucosa samples collected 80 days after birth and four
      weeks after the end of the feeding regimes revealed 275 differentially expressed
      loci. While the differentially expressed loci comprised 67 genes encoding
      proteins relevant to metabolism or metabolic adaptation, the most distinct
      difference between the two groups was the consistently lower activation of the
      immune system in calves that experienced restricted milk access compared to
      calves fed milk ad libitum. In conclusion, different early life milk diets had
      significant prolonged effects on the intestinal immune system.

PMID- 29374219
TI  - Depletion of HDAC1, 7 and 8 by Histone Deacetylase Inhibition Confers Elimination
      of Pancreatic Cancer Stem Cells in Combination with Gemcitabine.
AB  - Trichostatin A (TSA) possess histone deacetylase (HDAC) inhibitory potential, can
      reverse the deactivation of tumor suppressor genes and inhibit tumor cell
      proliferation. We evaluated the effect of TSA on HDAC expression, tumor cell
      proliferation, and cancer stem cells (CSCs) activities in pancreatic ductal
      adenocarnoma (PDAC) cells. The PDAC cell lines MiaPaCa-2 and PANC-1 were
      distinctly sensitive to TSA, with enhanced apoptosis, compared to SAHA. TSA or
      SAHA inhibited vimentin, HDACs 1, 7 and 8, upregulated E-cadherin mRNA and
      protein levels in the PDAC cells, and time-dependently downregulated Oct-4, Sox
      2, and Nanog, as well as inhibited PDAC tumorsphere formation. TSA also induces
      accumulation of acetylated histones, while increasing histone 3 lysine 4 or 9
      dimethylation levels in PDAC cells and enhancing the epigenetic activity of SAHA.
      The anti-CSCs effect of TSA was like that obtained by silencing HDAC-1 or 7 using
      siRNA, and enhances Gemcitabine activity. Our study highlights the molecular
      targetability of HDACs 1, 7, and 8, confirm their PDAC-CSCs maintaining role, and
      demonstrate that compared to SAHA, TSA modulates the epigenetically- mediated
      oncogenic activity of PDAC-CSCs, and potentiate Gemcitabine therapeutic activity,
      making a case for further exploration of TSA activity alone or in combination
      with Gemcitabine in PDAC therapy.

PMID- 29374220
TI  - Silica Gel Coated Spherical Micro resonator for Ultra-High Sensitivity Detection
      of Ammonia Gas Concentration in Air.
AB  - A silica gel coated microsphere resonator is proposed and experimentally
      demonstrated for measurements of ammonia (NH3) concentration in air with ultra
      high sensitivity. The optical properties of the porous silica gel layer change
      when it is exposed to low (parts per million (ppm)) and even ultra-low (parts per
      billion (ppb)) concentrations of ammonia vapor, leading to a spectral shift of
      the WGM resonances in the transmission spectrum of the fiber taper. The
      experimentally demonstrated sensitivity of the proposed sensor to ammonia is
      estimated as 34.46 pm/ppm in the low ammonia concentrations range from 4 ppm to
      30 ppm using an optical spectrum analyser (OSA), and as 800 pm/ppm in the ultra
      low range of ammonia concentrations from 2.5 ppb to 12 ppb using the frequency
      detuning method, resulting in the lowest detection limit (by two orders of
      magnitude) reported to date equal to 0.16 ppb of ammonia in air. In addition, the
      sensor exhibits excellent selectivity to ammonia and very fast response and
      recovery times measured at 1.5 and 3.6 seconds, respectively. Other attractive
      features of the proposed sensor are its compact nature, simplicity of
      fabrication.

PMID- 29374221
TI  - Fingerprint analysis of Huolingshengji Formula and its neuroprotective effects in
      SOD1G93A mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized
      by progressive loss of motor neurons. There are no definitive pathogenic
      mechanisms and effective treatments for ALS now. Traditional Chinese medicine
      (TCM) plays an important role in Chinese health care system. Huolingshengji
      Formula (HLSJ) is a TCM formula which is applied for treating flaccid syndrome.
      Our previous clinical study has indicated that HLSJ may have therapeutic effects
      in ALS patients. In the present study, we analyzed the chemical profile of HLSJ
      by the high-performance liquid chromatographic (HPLC) fingerprint analysis. And
      we investigated the therapeutic effects and neuroprotective mechanisms of HLSJ
      against ALS in SOD1G93A mouse model. Eleven typical peaks were identified by the
      fingerprint analysis of HLSJ, and the HPLC method had good precision,
      repeatability and stability. Consistent with our clinical studies, HLSJ
      significantly prolonged the lifespan, extended the disease duration, and
      prevented the motor neuron loss in the anterior horn of the lumbar spinal cords
      in SOD1G93A ALS model mice. Additionally, HLSJ alleviated the atrophy of the
      gastrocnemius muscles and ameliorated the apoptotic and inflammatory levels in
      the spinal cords of SOD1G93A mice. Collectively, our study indicated that HLSJ
      might be a novel candidate for the treatment of ALS.

PMID- 29374223
TI  - Integrated Optical Modulator Based on Transition between Photonic Bands.
AB  - An area efficient novel optical modulator with low operation voltage is designed
      based on integrated Mach-Zehnder Interferometer with a photonic crystal slab
      structure as the phase shifter. Plasma dispersion effect is utilized so that
      photonic band-to-band transition occurs at the operating frequency leading to a
      high index change (Deltan = ~4) for pi-phase shift on the modulator. This
      approach reduces the phase shifter length to a few micrometers (~5 um) in a
      silicon on insulator platform and operating voltage required is around 1 V. Low
      voltage together with short optical interaction length decrease optical losses
      and power consumption during modulation process providing a great opportunity for
      size and system cost optimization.

PMID- 29374222
TI  - Measuring dynamic social contacts in a rehabilitation hospital: effect of wards,
      patient and staff characteristics.
AB  - Understanding transmission routes of hospital-acquired infections (HAI) is key to
      improve their control. In this context, describing and analyzing dynamic inter
      individual contact patterns in hospitals is essential. In this study, we used
      wearable sensors to detect Close Proximity Interactions (CPIs) among patients and
      hospital staff in a 200-bed long-term care facility over 4 months. First, the
      dynamic CPI data was described in terms of contact frequency and duration per
      individual status or activity and per ward. Second, we investigated the
      individual factors associated with high contact frequency or duration using
      generalized linear mixed-effect models to account for inter-ward heterogeneity.
      Hospital porters and physicians had the highest daily number of distinct
      contacts, making them more likely to disseminate HAI among individuals.
      Conversely, contact duration was highest between patients, with potential
      implications in terms of HAI acquisition risk. Contact patterns differed among
      hospital wards, reflecting varying care patterns depending on reason for
      hospitalization, with more frequent contacts in neurologic wards and fewer,
      longer contacts in geriatric wards. This study is the first to report proximity
      sensing data informing on inter-individual contacts in long-term care settings.
      Our results should help better understand HAI spread, parameterize future
      mathematical models, and propose efficient control strategies.

PMID- 29374224
TI  - New role of phenothiazine derivatives as peripherally acting CB1 receptor
      antagonizing anti-obesity agents.
AB  - Developing peripherally active cannabinoid 1 (CB1) receptor antagonists is a
      novel therapeutic approach for the management of obesity. An unusual
      phenothiazine scaffold containing CB1R antagonizing hit was identified by
      adopting virtual screening work flow. The hit so identified was further modified
      by introducing polar functional groups into it to enhance the polar surface area
      and decrease the hydrophobicity of the resulting molecules. CB1 receptor
      antagonistic activity for the designed compounds was computed by the previously
      established pharmacophore and three dimensional quantitative structure-activity
      relationship models. Docking studies of these designed compounds confirmed the
      existence of favourable interactions within the active site of the CB1 receptor.
      The designed compounds were synthesized and evaluated for their CB1 receptor
      antagonistic activity. Parallel artificial membrane permeability assay was
      performed to evaluate their potential to permeate into the central nervous system
      wherein it was observed that the compounds did not possess the propensity to
      cross the blood brain barrier and would be devoid of central nervous system side
      effects. In pharmacological evaluation, the synthesized compounds (23, 25, 27 and
      34) showed significant decrease in food intake suggesting their potential
      application in the management of obesity through CB1 receptor antagonist
      activity.

PMID- 29374225
TI  - Long range haplotyping of paired-homologous chromosomes by single-chromosome
      sequencing of a single cell.
AB  - The longest possible haplotype is chromosome haplotype that is a set of co
      inherited alleles occurred on a single strand chromosome inherited from one
      parent. Standard whole-genome shotgun sequencing technologies are limited by the
      inability to independently study the haplotype of homologous chromosomes due to
      the short-reads sequencing strategy and disturbance of homologue chromosomes.
      Here, we investigated several types of chromosomal abnormalities by a dilution
      based method to separate an intact copy of homologous chromosome from human
      metaphase cells, and then single chromosomes were independently amplified by
      whole-genome amplification methods, converted into barcoded sequencing libraries,
      and sequenced in multiplexed pools by Illumina sequencers. We analyzed single
      chromosome derived from single metaphase cells of one patient with balanced
      chromosomal translocation t(3;5)(q24;q13), one patient with (47, XXY) karyotype
      and one with (47, XY, 21+) Down syndrome. We determined the translocation region
      of chromosomes in patient with t(3;5)(q24;q13) balanced chromosomal translocation
      by shallow whole-genome sequencing, which is helpful to pinpoint the chromosomal
      break point. We showed that SCS can physically separate and independently
      sequence three copies of chromosome 21 of Down syndrome patient. SCS has
      potential applications in personal genomics, single-cell genomics, and clinical
      diagnosis, particularly in revealing chromosomal level of genetic diseases.

PMID- 29374226
TI  - Impact of the huge 2011 Tohoku-oki tsunami on the phenotypes and genotypes of
      Japanese coastal threespine stickleback populations.
AB  - On March 11, 2011, a large earthquake occurred, causing a tsunami which struck
      the Pacific coast of northeast Japan. We investigated the ecological and genetic
      effects of the large tsunami on the threespine stickleback (genus Gasterosteus)
      populations in Otsuchi Town, which was one of the most severely damaged areas
      after the tsunami. Our environmental surveys showed that spring water may have
      contributed to the habitat recovery. Morphological analysis of the stickleback
      before and after the tsunami showed morphological shifts in the gill raker
      number, which is a foraging trait. Genetic analyses revealed that the allelic
      richness of one population was maintained after the tsunami, whereas that of
      another decreased in 2012 and then started to recover in 2013. Additionally, we
      found that the large tsunami and ground subsidence created new spring water-fed
      pools with sticklebacks, suggesting that the tsunami brought sticklebacks into
      these pools. Genetic analysis of this population showed that this population
      might be derived from hybridization between freshwater Gasterosteus aculeatus and
      anadromous G. nipponicus. Overall, our data indicate that tsunamis can influence
      morphologies and genetic structures of freshwater fishes. Furthermore, spring
      water may play important roles in the maintenance and creation of fish habitats,
      faced with environmental disturbance.

PMID- 29374227
TI  - A 'NanoSuit' successfully protects petals of cherry blossoms in high vacuum:
      examination of living plants in an FE-SEM.
AB  - Land plants have evolved on dry land and developed surface barriers to protect
      themselves from environmental stresses. We have previously reported that
      polymerization of a natural extracellular substance (ECS) on the outer surface of
      animals by electron beam or plasma irradiation, can give rise to a nano-scale
      layer, termed the "NanoSuit", which can keep small animals alive under the high
      vacuum of a scanning electron microscope (SEM). In the present research, we have
      focused on plants, using petals of cherry blossoms, as experimental specimens and
      examined their behavior under high vacuum conditions. Experiments on healthy
      living petals have demonstrated that without any pre-treatment, the overall
      morphology of specimens is well preserved and intact after imaging in an SEM,
      suggesting that natural substances on the petal surface behave like animal ECS
      and form a NanoSuit following irradiation with an electron beam. Furthermore, we
      have shown that the surface material can be extracted with chloroform and
      polymerized into a free-standing membrane by plasma irradiation. From our
      results, we conclude that surface materials, which have the ability to prevent
      water loss under natural conditions, increase the barrier ability and can protect
      plants under high vacuum conditions.

PMID- 29374228
TI  - The acute effects on duodenal gene expression in healthy men following
      consumption of a low-fat meal enriched with theobromine or fat.
AB  - Increasing apoA-I synthesis may improve HDL functionality and lower CVD risk. As
      theobromine and fat increase fasting apoA-I concentrations, and the intestine is
      involved in apoA-I production, the acute effects of both were studied on duodenal
      gene transcription to better understand underlying mechanisms. In this crossover
      study, 8 healthy men received once a low fat (LF) meal, a LF meal plus
      theobromine (850 mg), or a high fat (HF) meal. Five hours after meal intake
      duodenal biopsies were taken for microarray analysis. Theobromine and HF
      consumption did not change duodenal apoA-I expression. Theobromine did not change
      gene expression related to lipid and cholesterol metabolism, whereas those
      related to glycogen/glucose breakdown were downregulated. HF consumption
      increased gene expression related to lipid and cholesterol uptake and transport,
      and to glucose storage, while it decreased those related to glucose uptake.
      Furthermore, genes related to inflammation were upregulated, but inflammation
      markers in plasma were not changed. In healthy men, acute theobromine and fat
      consumption did not change duodenal apoA-I mRNA, but inhibited expression of
      genes related to glucose metabolism. Furthermore, HF intake activated in the
      duodenum expression of genes related to lipid and cholesterol metabolism and to
      inflammation.

PMID- 29374229
TI  - Pulsatile stretch as a novel modulator of amyloid precursor protein processing
      and associated inflammatory markers in human cerebral endothelial cells.
AB  - Amyloid beta (Abeta) deposition is a hallmark of Alzheimer's disease (AD).
      Vascular modifications, including altered brain endothelial cell function and
      structural viability of the blood-brain barrier due to vascular pulsatility, are
      implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature
      are often not considered in in vitro models of the blood-brain barrier. We
      demonstrate, for the first time, that pulsatile stretch of brain vascular
      endothelial cells modulates amyloid precursor protein (APP) expression and the
      APP processing enzyme, beta-secretase 1, eventuating increased-Abeta generation
      and secretion. Concurrent modulation of intercellular adhesion molecule 1 and
      endothelial nitric oxide synthase (eNOS) signaling (expression and
      phosphorylation of eNOS) in response to pulsatile stretch indicates parallel
      activation of endothelial inflammatory pathways. These findings mechanistically
      support vascular pulsatility contributing towards cerebral Abeta levels.

PMID- 29374230
TI  - Targeted and Untargeted Metabolic Profiling of Wild Grassland Plants identifies
      Antibiotic and Anthelmintic Compounds Targeting Pathogen Physiology, Metabolism
      and Reproduction.
AB  - Plants traditionally used by farmers to manage livestock ailments could reduce
      reliance on synthetic antibiotics and anthelmintics but in many cases their
      chemical composition is unknown. As a case study, we analyzed the metabolite
      profiles of 17 plant species and 45 biomass samples from agricultural grasslands
      in England using targeted and untargeted metabolite profiling by liquid
      chromatography mass spectrometry. We identified a range of plant secondary
      metabolites, including 32 compounds with known antimicrobial/anthelmintic
      properties which varied considerably across the different plant samples. These
      compounds have been shown previously to target multiple aspects of pathogen
      physiology and metabolism in vitro and in vivo, including inhibition of quorum
      sensing in bacteria and egg viability in nematodes. The most abundant bioactive
      compounds were benzoic acid, myricetin, p-coumaric acid, rhamnetin, and
      rosmarinic acid. Four wild plants (Filipendula ulmaria (L.) Maxim., Prunella
      vulgaris L., Centuarea nigra L., and Rhinanthus minor L.) and two forage legumes
      (Medicago sativa L., Trifolium hybridium L.) contained high levels of these
      compounds. Forage samples from native high-diversity grasslands had a greater
      abundance of medicinal compounds than samples from agriculturally improved
      grasslands. Incorporating plants with antibiotic/anthelmintic compounds into
      livestock feeds may reduce global drug-resistance and preserve the efficacy of
      last-resort drugs.

PMID- 29374231
TI  - Modulation of oncogenic miRNA biogenesis using functionalized polyamines.
AB  - MicroRNAs are key factors in the regulation of gene expression and their
      deregulation has been directly linked to various pathologies such as cancer. The
      use of small molecules to tackle the overexpression of oncogenic miRNAs has
      proved its efficacy and holds the promise for therapeutic applications. Here we
      describe the screening of a 640-compound library and the identification of
      polyamine derivatives interfering with in vitro Dicer-mediated processing of the
      oncogenic miR-372 precursor (pre-miR-372). The most active inhibitor is a
      spermine-amidine conjugate that binds to the pre-miR-372 with a KD of 0.15 uM,
      and inhibits its in vitro processing with a IC50 of 1.06 uM. The inhibition of
      miR-372 biogenesis was confirmed in gastric cancer cells overexpressing miR-372
      and a specific inhibition of proliferation through de-repression of the tumor
      suppressor LATS2 protein, a miR-372 target, was observed. This compound modifies
      the expression of a small set of miRNAs and its selective biological activity has
      been confirmed in patient-derived ex vivo cultures of gastric carcinoma.
      Polyamine derivatives are promising starting materials for future studies about
      the inhibition of oncogenic miRNAs and, to the best of our knowledge, this is the
      first report about the application of functionalized polyamines as miRNAs
      interfering agents.

PMID- 29374232
TI  - A dynamic allosteric pathway underlies Rad50 ABC ATPase function in DNA repair.
AB  - The Mre11-Rad50 protein complex is an initial responder to sites of DNA double
      strand breaks. Many studies have shown that ATP binding to Rad50 causes global
      changes to the Mre11-Rad50 structure, which are important for DNA repair
      functions. Here we used methyl-based NMR spectroscopy on a series of mutants to
      describe a dynamic allosteric pathway within Rad50. Mutations result in changes
      in the side chain methyl group chemical environment that are correlated with
      altered nanosecond timescale dynamics. We also observe striking relationships
      between the magnitude of chemical shift perturbations and Rad50 and Mre11
      activities. Together, these data suggest an equilibrium between a ground state
      and an "active" dimerization competent state of Rad50 that has locally altered
      structure and dynamics and is poised for ATP-induced dimerization and eventual
      ATP hydrolysis. Thus, this sparsely populated intermediate is critical for Mre11
      Rad50-directed DNA double strand break repair.

PMID- 29374234
TI  - Prevention of Invasive Aspergillus Fungal Infections with the Suspension and
      Delayed-Release Tablet Formulations of Posaconazole in Patients with Haematologic
      Malignancies.
AB  - Posaconazole is a triazole antifungal used to prevent invasive fungal infections
      (IFIs) in patients receiving chemotherapy or haemotopoietic stem cell
      transplantation. Due to highly variable bioavailability of the oral suspension
      formulation, a delayed-release tablet was developed which showed improved
      bioavailability. A minimal target posaconazole plasma concentration of 0.7 mg/L
      is recommended for prophylaxis of IFIs. However, the relationship between plasma
      concentration of posaconazole and its efficacy against IFIs remains unclear. We
      analysed trough posaconazole concentrations and response against IFIs in 50 and
      104 patients with haematologic malignancies receiving prophylactic posaconazole
      as the tablet or suspension formulation, respectively. Mean plasma concentration
      of posaconazole was 1.91 +/- 1.06 mg/L and 0.82 +/- 0.57 mg/L in the tablet and
      the oral suspension group, respectively (p < 0.0001). The percentage of patients
      reaching the minimal target concentration of 0.7 mg/L was 92.0% and 47.1% in the
      tablet and oral suspension groups, respectively (p < 0.0001). Emergent
      aspergillosis occurred in 9 (8.7%) patients in the suspension group and in none
      of the patients taking the tablet formulation (p = 0.032). Our results show a
      relationship between plasma concentrations of posaconazole and its prophylactic
      efficacy in patients with haematologic malignancies. Target posaconazole
      concentrations are reached more efficiently with the tablet than with the
      suspension formulation.

PMID- 29374235
TI  - The effect of environmental factors and migration dynamics on the prevalence of
      antibiotic-resistant Escherichia coli in estuary environments.
AB  - Understanding the antibiotic resistance transmission mechanisms and migration
      dynamics of antibiotic-resistant bacteria (ARB) in the natural environment is
      critical given the increasing prevalence of antibiotic resistance. The aim of
      this study was to examine the fate of sulfonamide-resistant fecal bacteria (E.
      coli) in an estuary ecosystem and to explore the role and contribution of
      environmental factors in this process. The prevalence of sulfonamide-resistance
      status of E. coli was analyzed over different seasons in two estuary systems.
      Environmental factors and disturbance indices of anthropogenic activities were
      evaluated by detecting antibiotic concentrations, heavy metal abundance and other
      physicochemical parameters. The abundances of antibiotic-resistant E. coli were
      significantly attenuated during land-sea migration suggesting that estuary
      environments play a natural mitigation role in the contamination of freshwaters
      by antibiotic-resistant E. coli. Additionally, environmental factors and
      disturbance indices of anthropogenic activities significantly correlated with the
      distribution and migration of antibiotic-resistant E. coli in the estuaries.
      Lastly, simulation experiments suggested differential adaptability between
      antibiotic-resistant and non-resistant E. coli towards environmental changes in
      estuary environments. Meanwhile, our results indicate that low concentrations of
      antibiotics will not increase the competitive advantage of resistant E. coli in
      estuaries.

PMID- 29374237
TI  - Role of fluorine in two-dimensional dichalcogenide of SnSe 2.
AB  - Authors report an effect of F substitution on layered SnSe2 through the
      successful synthesis of polycrystalline SnSe2-deltaF x (0.000 <= x <= 0.010) by
      solid-state reaction. Accompanied with density functional theory calculations,
      the blue shift of A1g peak in Raman spectra reveal that F- ions are substituted
      at Se vacancy sites as decreasing the reduced mass of vibrational mode associated
      with Sn-Se bonding. From the measurements of electrical parameters, conductivity
      as well as carrier concentration are governed by thermally activated behavior,
      while such behavior is suppressed in Hall mobility, which occurs as F ratio
      increases. Based on Arrhenius relation, it is found that the potential barrier
      height at the grain boundary is suppressed with increasing F amount, suggesting
      that the F- ion is a promising candidate for the grain boundary passivation in
      the two-dimensional dichalcogenide system.

PMID- 29374233
TI  - GWAS of epigenetic aging rates in blood reveals a critical role for TERT.
AB  - DNA methylation age is an accurate biomarker of chronological age and predicts
      lifespan, but its underlying molecular mechanisms are unknown. In this genome
      wide association study of 9907 individuals, we find gene variants mapping to five
      loci associated with intrinsic epigenetic age acceleration (IEAA) and gene
      variants in three loci associated with extrinsic epigenetic age acceleration
      (EEAA). Mendelian randomization analysis suggests causal influences of menarche
      and menopause on IEAA and lipoproteins on IEAA and EEAA. Variants associated with
      longer leukocyte telomere length (LTL) in the telomerase reverse transcriptase
      gene (TERT) paradoxically confer higher IEAA (P < 2.7 * 10-11). Causal modeling
      indicates TERT-specific and independent effects on LTL and IEAA. Experimental
      hTERT-expression in primary human fibroblasts engenders a linear increase in DNA
      methylation age with cell population doubling number. Together, these findings
      indicate a critical role for hTERT in regulating the epigenetic clock, in
      addition to its established role of compensating for cell replication-dependent
      telomere shortening.

PMID- 29374236
TI  - SOX2 activation predicts prognosis in patients with head and neck squamous cell
      carcinoma.
AB  - SOX2 copy number and mRNA expression were analysed to examine the clinical
      significance of SOX2 activation in HNSCC. Gene expression signatures reflecting
      SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were
      classified into two subgroups according to the gene expression signature: SOX2
      high and SOX2-low. The clinical significance of SOX2 activation was further
      validated in two independent cohorts. Moreover, clinical significance of SOX2
      activation in response to radiotherapy was assessed in patients with HNSCC. The
      relationship between SOX2 activation and radiotherapy was validated in an in
      vitro experiment. Patients in the SOX2-high subgroup had a better prognosis than
      patients in the SOX2-low subgroup in all three patient cohorts. Results of
      multivariate regression analysis showed that SOX2 signature was an independent
      predictor of the overall survival of patients with HNSCC (hazard ratio, 1.45; 95%
      confidence interval, 1.09-1.92; P = 0.01). Interestingly, SOX2 activation was a
      predictor of therapy outcomes in patients receiving radiotherapy. Moreover, SOX2
      overexpression enhanced the effect of radiotherapy in HNSCC cell lines. SOX2
      activation is associated with improved prognosis of patients with HNSCC and might
      be used to predict which patients might benefit from radiotherapy.

PMID- 29374238
TI  - Transcriptional Regulation on Aneuploid Chromosomes in Divers Candida albicans
      Mutants.
AB  - Candida albicans is a diploid fungus and a predominant opportunistic human
      pathogen. Notably, C. albicans employs reversible chromosomal aneuploidies as a
      means of survival in adverse environments. We previously characterized
      transcription on the monosomic chromosome 5 (Ch5) that arises with adaptation to
      growth on the toxic sugar sorbose in the mutant Sor125(55). We now extend this
      analysis to the trisomic hybrid Ch4/7 within Sor125(55) and a diverse group of
      three mutants harboring a single Ch5. We find a similar pattern of
      transcriptional changes on either type of aneuploid chromosome within these
      mutants wherein expression of many genes follows chromosome ploidy, consistent
      with a direct mechanism to regulate genes important for adaptation to growth. In
      contrast, a significant number of genes are expressed at the disomic level,
      implying distinct mechanisms compensating for gene dose on monosomic or trisomic
      chromosomes consistent with maintaining cell homeostasis. Finally, we find
      evidence for an additional mechanism that elevates expression of genes on normal
      disomic Ch4 and Ch7 in mutants to levels commensurate with that found on the
      trisomic Ch4/7b in Sor125(55). Several of these genes are similarly
      differentially regulated among mutants, suggesting they play key functions in
      either maintaining aneuploidy or adaptation to growth conditions.

PMID- 29374239
TI  - Optimizing OCT acquisition parameters for assessments of vitreous haze for
      application in uveitis.
AB  - Detection and evaluation of inflammatory activity in uveitis is essential to the
      management of the condition, and yet continues to be largely dependent on
      subjective clinical measures. Optical coherence tomography (OCT) measurement of
      vitreous activity is an alternative to clinical vitreous haze scoring and has
      passed a number of early validation studies. In this study we aimed to evaluate
      the impact of 'operator factors' on the variability of the technique as part of
      the validation process, and to help evaluate its suitability for 'real world'
      use. Vitreous haze index was calculated as a ratio between the reflectivity of
      the vitreous and of the outer retina in each scan. Different scanning conditions
      were tested and their effect on the measurement is reported. Our results show
      that the 'quantitative imaging' technique of OCT-measured vitreous activity had
      good reliability in normal subjects under a range of 'real world' conditions,
      such as when the operator changes the averaging value. The technique was however
      vulnerable to highly inaccurate focussing or abnormal downward displacement of
      the image. OCT-based quantification of vitreous activity is a promising
      alternative to current subjective clinical estimates, with sufficient 'tolerance'
      to be used in routine clinical practice as well as clinical trials.

PMID- 29374240
TI  - Positive interactions of major-effect QTLs with genetic background that enhances
      rice yield under drought.
AB  - To improve the grain yield of the lowland-adapted popular rice variety Samba
      Mahsuri under reproductive-stage drought (RS) and to understand the interactions
      between drought QTLs, two mapping populations were developed using marker
      assisted selection (MAS) and marker-assisted recurrent selection (MARS). The mean
      grain yield of pyramided lines (PLs) with qDTY 2.2  + qDTY 4.1 in MAS is
      significantly higher under RS and irrigated control than lines with single QTLs.
      Among MARS PLs, lines with four qDTYs (qDTY 1.1  + qDTY 2.1  + qDTY 3.1  + qDTY
      11.1 ) and two QTLs (qDTY 1.1  + qDTY 11.1 ) yielded higher than PLs with other
      qDTY combinations. The selected PLs showed a yield advantage of 0.3-2.0 t ha-1
      under RS. An allelic profile of MAS PLs having same qDTY combination but with
      different yields under drought was studied. Hierarchical clustering grouped
      together the selected lines with high yield under drought. Epistasis test showed
      the interaction of qDTY 4.1 and qDTY 9.1 loci with qDTY 7.1 significantly
      increased yield under drought and all the lines with higher yield under drought
      possessed the conserved region of qDTY 7.1 on chromosome 7. The positive
      interactions among QTLs, effectiveness of QTLs in different backgrounds,
      introgression of DTY QTLs together with resistance to biotic stresses shall help
      enhance grain yield under RS.

PMID- 29374241
TI  - Dual regulation of activity and intracellular localization of the PASTA kinase
      PrkC during Bacillus subtilis growth.
AB  - The activity of the PrkC protein kinase is regulated in a sophisticated manner in
      Bacillus subtilis cells. In spores, in the presence of muropeptides, PrkC
      stimulates dormancy exit. The extracellular region containing PASTA domains binds
      peptidoglycan fragments to probably enhance the intracellular kinase activity.
      During exponential growth, the cell division protein GpsB interacts with the
      intracellular domain of PrkC to stimulate its activity. In this paper, we have
      reinvestigated the regulation of PrkC during exponential and stationary phases.
      We observed that, during exponential growth, neither its septal localization nor
      its activity are influenced by the addition of peptidoglycan fragments or by the
      deletion of one or all PASTA domains. However, Dynamic Light Scattering
      experiments suggest that peptidoglycan fragments bind specifically to PrkC and
      induce its oligomerization. In addition, during stationary phase, PrkC appeared
      evenly distributed in the cell wall and the deletion of one or all PASTA domains
      led to a non-activated kinase. We conclude that PrkC activation is not as
      straightforward as previously suggested and that regulation of its kinase
      activity via the PASTA domains and peptidoglycan fragments binding occurs when
      PrkC is not concentrated to the bacterial septum, but all over the cell wall in
      non-dividing bacillus cells.

PMID- 29374242
TI  - Population coding of grasp and laterality-related information in the macaque
      fronto-parietal network.
AB  - Preparing and executing grasping movements demands the coordination of sensory
      information across multiple scales. The position of an object, required hand
      shape, and which of our hands to extend must all be coordinated in parallel. The
      network formed by the macaque anterior intraparietal area (AIP) and hand area
      (F5) of the ventral premotor cortex is essential in the generation of grasping
      movements. Yet, the role of this circuit in hand selection is unclear. We
      recorded from 1342 single- and multi-units in AIP and F5 of two macaque monkeys
      (Macaca mulatta) during a delayed grasping task in which monkeys were instructed
      by a visual cue to perform power or precision grips on a handle presented in five
      different orientations with either the left or right hand, as instructed by an
      auditory tone. In AIP, intended hand use (left vs. right) was only weakly
      represented during preparation, while hand use was robustly present in F5 during
      preparation. Interestingly, visual-centric handle orientation information
      dominated AIP, while F5 contained an additional body-centric frame during
      preparation and movement. Together, our results implicate F5 as a site of visuo
      motor transformation and advocate a strong transition between hand-independent
      and hand-dependent representations in this parieto-frontal circuit.

PMID- 29374243
TI  - Large Area Radial Junction Silicon Nanowire Solar Mini-Modules.
AB  - In this work, we introduce the demonstration of 5 * 5 cm2 mini-modules based on
      radial junction silicon nanowire (RJ SiNW) devices grown by plasma-assisted vapor
      liquid-solid (VLS) technique. The mini-modules are obtained thanks to an
      industrial laser scribing technique. The electrical parameters have been
      highlighted to address the performance of these devices and perspectives towards
      competitive RJ SiNW solar modules. Moreover, electroluminescence (EL)
      measurements were also conducted to assess the uniformity of the fabricated mini
      modules. In addition, the structural characterization of solar cells and laser
      scribed lines has been assessed by scanning electron microscopy (SEM). The
      challenges and perspectives are also discussed.

PMID- 29374244
TI  - Ischemia Reperfusion Injury after Gradual versus Rapid Flow Restoration for
      Middle Cerebral Artery Occlusion Rats.
AB  - Ischemia-reperfusion injury (IRI) is an important cause of adverse prognosis
      after recanalization in patients with acute occlusion of major intracranial
      artery (AOMIA). Here, we provided data indicating that gradual flow restoration
      (GFR) would be superior to rapid flow restoration (RFR) in alleviating cerebral
      IRIs in middle cerebral artery occlusion (MCAO) rats. A total of 94 MCAO rats
      with 15, 30 and 60-minute occlusion were randomly assigned to receive either GFR
      or RFR intervention. There were significant differences between GFR and RFR group
      in mean neurological severity score (1.02 versus 1.28; p < 0.05), median infarct
      ratio (0.016 versus 0.12; p < 0.001), median neuronal apoptosis ratio (1.81
      versus 14.46; p < 0.001), and mean histopathological abnormality score (0.92
      versus 1.66; p < 0.001). In addition, these differences were mainly distributed
      in 30-minute and 60-minute occlusion rats, not in 15-minute occlusion rats. These
      results indicated that GFR rather than RFR could effectively alleviate cerebral
      IRIs in MCAO rats, especially in rats with longer occlusion duration, suggesting
      that GFR may be particularly applicable to AOMIA patients who are presented to
      neurointerventionalists in the later-time of recanalization therapy window.

PMID- 29374245
TI  - Identifying Hallmark Symptoms of Developmental Prosopagnosia for Non-Experts.
AB  - Developmental prosopagnosia (DP) is characterised by a severe and relatively
      selective deficit in face recognition, in the absence of neurological injury.
      Because public and professional awareness of DP is low, many adults and children
      are not identified for formal testing. This may partly result from the lack of
      appropriate screening tools that can be used by non-experts in either
      professional or personal settings. To address this issue, the current study
      sought to (a) explore when DP can first be detected in oneself and another, and
      (b) identify a list of the condition's everyday behavioural manifestations.
      Questionnaires and interviews were administered to large samples of adult DPs,
      their unaffected significant others, and parents of children with the condition;
      and data were analysed using inductive content analysis. It was found that DPs
      have limited insight into their difficulties, with most only achieving
      realisation in adulthood. Nevertheless, the DPs' reflections on their childhood
      experiences, together with the parental responses, revealed specific indicators
      that can potentially be used to spot the condition in early childhood. These
      everyday hallmark symptoms may aid the detection of individuals who would benefit
      from objective testing, in oneself (in adults) or another person (for both adults
      and children).

PMID- 29374247
TI  - Author Correction: Plant spatial patterns identify alternative ecosystem
      multifunctionality states in global drylands.
AB  - In the version of this Article originally published, the values of two of the
      functions used to calculate the multifunctionality index were incorrect, which
      affected Figs 3,4 of the main article and Supplementary Figs 3,4,5,6,9. Please
      see the correction notice for full details.

PMID- 29374246
TI  - Lignin and cellulose dynamics with straw incorporation in two contrasting
      cropping soils.
AB  - Incorporation of crop residues is essential to enhance soil organic matter in
      arable ecosystems. Here, we monitored the dynamics of cellulose and lignin, the
      most abundant constituents of plant residues, and their relationships with enzyme
      activities, microbial gene abundances and soil properties after 13-year long-term
      and one-year short-term crop straw incorporation into upland and upland-paddy
      soils in a field-based experiment. Lignin, rather than cellulose, accumulated in
      both soils following straw incorporation. Cellulose was almost completely
      converted into non-cellulose forms within 6 and 3 months after straw
      incorporation into upland and upland-paddy rotation soils, respectively. Whereas,
      lignin accumulated at the rate of 129 and 137 mg kg-1 yr-1 within 13 years' straw
      incorporation in upland and upland-paddy rotation, respectively. The predominance
      of recalcitrant vanillyl monomers in upland-paddy rotation indicated a high
      stability of lignin. Structural equation models revealed that the key factor
      driving cellulose and lignin dynamics was available nitrogen, followed by enzymes
      activities (cellobiohydrolases and laccases) and functional genes abundances
      (cbhI and laccase-like) as mediated by soil pH. Our findings highlighted that
      upland might have higher carbon sequestration rate, whereas upland-paddy rotation
      system was more beneficial for accumulation of recalcitrant organic fractions
      under crop residue incorporation.

PMID- 29374249
TI  - The optimal dosage regimen of vitamin D supplementation for correcting deficiency
      in adolescents: a pilot randomized controlled trial.
AB  - BACKGROUND/OBJECTIVES: Vitamin D deficiency is common in adolescents but the
      optimal dosage regimen for correcting deficiency is unknown. To test the safety
      and efficacy of two different vitamin D dosage regimens to correct vitamin D
      deficiency in adolescents. SUBJECTS/METHODS: In this 12-month, double-blind,
      randomized placebo-controlled trial, 28 adolescents (serum 25 hydroxyvitamin D
      (25(OH)D) of 21 to 50 nmol/L) were randomly assigned to one of three groups:
      monthly (n = 9; vitamin D3 50,000 IU orally monthly plus three placebo tablets 3
      monthly), 3-monthly (n = 9; 150,000 IU (3 * 50,000 IU tablets) 3-monthly and
      placebo orally monthly), or placebo (n = 10; placebo monthly and three placebo
      tablets 3-monthly). Serum 25(OH)D was measured at baseline, 3, 6 and 12 months.
      RESULTS: Two participants withdrew after their baseline measurement from the 3
      monthly group. At 12 months, one participant was deficient (<=50 nmol/L) in both
      the monthly and 3-monthly groups, whereas six out of ten in the placebo remained
      deficient (P = 0.055). At 12 months, the average serum 25(OH)D levels for the
      monthly, 3-monthly and placebo groups were 76.4, 64.7 and 49.7 nmol/L,
      respectively (P < 0.001 and P = 0.04 for differences between monthly and placebo
      groups and 3-monthly and placebo groups respectively, after adjustment for age,
      sex and seasonal variation). Adherence was 100% and adverse events were minor.
      CONCLUSIONS: Both 50,000 IU monthly and 150,000 IU 3-monthly of vitamin D3 safely
      and effectively corrects vitamin D deficiency in adolescents. These data provide
      treatment options which can be used by health practitioners to tailor vitamin D
      dosage regiments according to patient preference and context.

PMID- 29374248
TI  - Role of Quzhou Fructus Aurantii Extract in Preventing and Treating Acute Lung
      Injury and Inflammation.
AB  - Quzhou Fructus Aurantii (QFA) is an authentic herb of local varieties in
      Zhejiang, China, which is usually used to treat gastrointestinal illnesses, but
      its effects on respiratory inflammation have not been reported yet. In our study,
      the anti-inflammatory activity of QFA extract (QFAE) was evaluated on copper
      sulfate pentahydrate (CuSO4.5H2O)-induced transgenic neutrophil fluorescent
      zebrafish model. QFAE showed a significant effect of anti-inflammation in
      CuSO4.5H2O-induced zebrafish by reducing the neutrophil number in the
      inflammatory site. We investigated the anti-inflammatory activity of QFAE on
      lipopolysaccharide (LPS)-induced acute lung injury (ALI) mice models and RAW
      264.7 cells. QFAE had an anti-inflammatory effect on reducing total cells,
      neutrophils, and macrophages in BALF and attenuated alveolus collapse,
      neutrophils infiltration, lung W/D ratio, myeloperoxidase (MPO) protein
      expression and other pulmonary histological changes in lung tissues, as well as
      hematological changes. Levels of pro-inflammatory cytokines, including TNF, IL-6,
      IFN-gamma, MCP-1, and IL-12p70, were decreased, whereas anti-inflammatory
      cytokine IL-10 was increased after treatment with QFAE both in vivo and in vitro.
      In summary, our results suggested that QFAE had apparent anti-inflammatory
      effects on CuSO4.5H2O-induced zebrafish, LPS-induced ALI mice, and RAW 264.7
      cells. Furthermore, QFAE may be a therapeutic drug to treat ALI/ARDS and other
      respiratory inflammations.

PMID- 29374250
TI  - Activated forms of astrocytes with higher GLT-1 expression are associated with
      cognitive normal subjects with Alzheimer pathology in human brain.
AB  - Although the cognitive impairment in Alzheimer's disease (AD) is believed to be
      caused by amyloid-beta (Abeta) plaques and neurofibrillary tangles (NFTs),
      several postmortem studies have reported cognitive normal subjects with AD brain
      pathology. As the mechanism underlying these discrepancies has not been
      clarified, we focused the neuroprotective role of astrocytes. After examining 47
      donated brains, we classified brains into 3 groups, no AD pathology with no
      dementia (N-N), AD pathology with no dementia (AD-N), and AD pathology with
      dementia (AD-D), which represented 41%, 21%, and 38% of brains, respectively. No
      differences were found in the accumulation of Abeta plaques or NFTs in the
      entorhinal cortex (EC) between AD-N and AD-D. Number of neurons and synaptic
      density were increased in AD-N compared to those in AD-D. The astrocytes in AD-N
      possessed longer or thicker processes, while those in AD-D possessed shorter or
      thinner processes in layer I/II of the EC. Astrocytes in all layers of the EC in
      AD-N showed enhanced GLT-1 expression in comparison to those in AD-D. Therefore
      these activated forms of astrocytes with increased GLT-1 expression may exert
      beneficial roles in preserving cognitive function, even in the presence of Abeta
      and NFTs.

PMID- 29374252
TI  - Pioneering the chromatin landscape.

PMID- 29374251
TI  - A two-step synthesis of nanosheet-covered fibers based on alpha-Fe2O3/NiO
      composites towards enhanced acetone sensing.
AB  - A novel hierarchical heterostructures based on alpha-Fe2O3/NiO nanosheet-covered
      fibers were synthesized using a simple two-step process named the electrospinning
      and hydrothermal techniques. A high density of alpha-Fe2O3 nanosheets were
      uniformly and epitaxially deposited on a NiO nanofibers. The crystallinity,
      morphological structure and surface composition of nanostructured based on alpha
      Fe2O3/NiO composites were investigated by XRD, SEM, TEM, EDX, XPS and BET
      analysis. The extremely branched alpha-Fe2O3/NiO nanosheet-covered fibers
      delivered an extremely porous atmosphere with huge specific surface area
      essential for superior gas sensors. Different nanostructured based on alpha
      Fe2O3/NiO composites were also explored by adjusting the volume ratio of the
      precursors. The as-prepared samples based on alpha-Fe2O3/NiO nanocomposite
      sensors display apparently enhanced sensing characteristics, including higher
      sensing response, quick response with recovery speed and better selectivity
      towards acetone gas at lower operating temperature as compared to bare NiO
      nanofibers. The sensing response of S-2 based alpha-Fe2O3/NiO nanosheet-covered
      fibers were 18.24 to 100 ppm acetone gas at 169  degrees C, which was about 6.9
      times higher than that of bare NiO nanofibers. The upgraded gas sensing
      performance of composites based on alpha-Fe2O3/NiO nanosheet-covered fibers might
      be ascribed to the exclusive morphologies with large surface area, p-n
      heterojunctions and the synergetic performance of alpha-Fe2O3 and NiO.

PMID- 29374253
TI  - DNA.Land is a framework to collect genomes and phenomes in the era of abundant
      genetic information.

PMID- 29374254
TI  - ADCY3, neuronal primary cilia and obesity.

PMID- 29374255
TI  - Our shared history.

PMID- 29374256
TI  - Screening a small molecule library to identify inhibitors of NF-kappaB inducing
      kinase and pro-labor genes in human placenta.
AB  - The non-canonical NF-kappaB signaling (RelB/p52) pathway drives pro-labor genes
      in the human placenta, including corticotropin-releasing hormone (CRH) and
      cyclooxygenase-2 (COX-2), making this a potential therapeutic target to delay
      onset of labor. Here we sought to identify small molecule compounds from a pre
      existing chemical library of orally active drugs that can inhibit this NF-kappaB
      signaling, and in turn, human placental CRH and COX-2 production. We used a cell
      based assay coupled with a dual-luciferase reporter system to perform an in vitro
      screening of a small molecule library of 1,120 compounds for inhibition of the
      non-canonical NF-kappaB pathway. Cell toxicity studies and drug efflux transport
      MRP1 assays were used to further characterize the lead compounds. We have found
      that 14 drugs have selective inhibitory activity against lymphotoxin beta complex
      induced activation of RelB/p52 in HEK293T cells, several of which also inhibited
      expression of CRH and COX-2 in human term trophoblast. We identified
      sulfapyridine and propranolol with activity against CRH and COX-2 that deserve
      further study. These drugs could serve as the basis for development of orally
      active drugs to affect length of gestation, first in an animal model, and then in
      clinical trials to prevent preterm birth during human pregnancy.

PMID- 29374257
TI  - Differential physiological responses and tolerance to potentially toxic elements
      in biodiesel tree Jatropha curcas.
AB  - Environmental pollution by potentially toxic elements (PTEs) has become a serious
      problem with increasing industrialization and the disturbance of natural
      biogeochemical cycles. Jatropha is an oilseed-bearing shrub with high potential
      for biodiesel production in arid regions. In this study, we examined the
      physiological responses of this plant to five representative PTEs (Cd, Cr, Cu,
      Ni, and Zn) in a hydroponic culture. Application of higher concentrations of Cd
      and Zn led to severe leaf chlorosis, and Cd, Cu, and Ni treatments resulted in
      significant growth retardation. Higher enrichment of the applied PTEs in the
      shoots was observed for Zn- and Cd-treated plants, with the latter reaching 24
      fold enrichment in plants exposed to 10 MUM Cd, suggesting that Jatropha can cope
      with relatively higher internal concentrations of toxic Cd. Although Cd stress
      led to the disturbance of essential mineral homeostasis and photosynthesis, this
      induced an increase in thiol compounds in the roots, suggesting defensive
      responses of Jatropha to PTEs. This study showed that Jatropha exhibits distinct
      sensitivities and physiological responses to different PTEs. This study also
      provides basic knowledge for diagnosing the physiological status of Jatropha
      trees for potential dual use in afforestation and as a sustainable energy supply.

PMID- 29374259
TI  - Interplay of bimolecular and Auger recombination in photoexcited carrier dynamics
      in silicon nanocrystal/silicon dioxide superlattices.
AB  - We report results of investigating carrier recombination in silicon
      nanocrystal/silicon dioxide superlattices. The superlattices prepared by nitrogen
      free plasma enhanced chemical vapour deposition contained layers of silicon
      nanocrystals. Femtosecond transient transmission optical spectroscopy was used to
      monitor carrier mechanisms in the samples. The three-particle Auger recombination
      was observed in accord with previous reports. However, under high pump
      intensities (high photoexcited carrier densities) the bimolecular process
      dominated the recombination. Detailed analysis of measured data and fitting
      procedure made it possible to follow and quantify the interplay between the two
      recombination processes. The bimolecular recombination was interpreted in terms
      of the trap-assisted Auger recombination.

PMID- 29374258
TI  - Identification of a Golgi GPI-N-acetylgalactosamine transferase with tandem
      transmembrane regions in the catalytic domain.
AB  - Many eukaryotic proteins are anchored to the cell surface via the glycolipid
      glycosylphosphatidylinositol (GPI). Mammalian GPIs have a conserved core but
      exhibit diverse N-acetylgalactosamine (GalNAc) modifications, which are added via
      a yet unresolved process. Here we identify the Golgi-resident GPI-GalNAc
      transferase PGAP4 and show by mass spectrometry that PGAP4 knockout cells lose
      GPI-GalNAc structures. Furthermore, we demonstrate that PGAP4, in contrast to
      known Golgi glycosyltransferases, is not a single-pass membrane protein but
      contains three transmembrane domains, including a tandem transmembrane domain
      insertion into its glycosyltransferase-A fold as indicated by comparative
      modeling. Mutational analysis reveals a catalytic site, a DXD-like motif for UDP
      GalNAc donor binding, and several residues potentially involved in acceptor
      binding. We suggest that a juxtamembrane region of PGAP4 accommodates various GPI
      anchored proteins, presenting their acceptor residue toward the catalytic center.
      In summary, we present insights into the structure of PGAP4 and elucidate the
      initial step of GPI-GalNAc biosynthesis.

PMID- 29374260
TI  - Configurable topological textures in strain graded ferroelectric nanoplates.
AB  - Topological defects in matter behave collectively to form highly non-trivial
      structures called topological textures that are characterised by conserved
      quantities such as the winding number. Here we show that an epitaxial
      ferroelectric square nanoplate of bismuth ferrite subjected to a large strain
      gradient (as much as 105 m-1) associated with misfit strain relaxation enables
      five discrete levels for the ferroelectric topological invariant of the entire
      system because of its peculiar radial quadrant domain texture and its inherent
      domain wall chirality. The total winding number of the topological texture can be
      configured from - 1 to 3 by selective non-local electric switching of the
      quadrant domains. By using angle-resolved piezoresponse force microscopy in
      conjunction with local winding number analysis, we directly identify the
      existence of vortices and anti-vortices, observe pair creation and annihilation
      and manipulate the net number of vortices. Our findings offer a useful concept
      for multi-level topological defect memory.

PMID- 29374261
TI  - HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to
      entecavir: structural insights into HBV-RT inhibition by entecavir.
AB  - Hepatitis B virus (HBV) reverse transcriptase (RT) is essential for viral
      replication and is an important drug target. Nonetheless, the notorious
      insolubility of HBV RT has hindered experimental structural studies and structure
      based drug design. Here, we demonstrate that a Q151M substitution alone at the
      nucleotide-binding site (N-site) of human immunodeficiency virus type-1 (HIV-1)
      RT renders HIV-1 highly sensitive to entecavir (ETV), a potent nucleoside
      analogue RT inhibitor (NRTI) against HBV. The results suggest that Met151 forms a
      transient hydrophobic interaction with the cyclopentyl methylene of ETV, a
      characteristic hydrophobic moiety of ETV. We thus solved the crystal structures
      of HIV-1 RTQ151M:DNA complex with bound dGTP or ETV-triphosphate (ETV-TP). The
      structures revealed that ETV-TP is accommodated at the N-site slightly apart from
      the ribose ring of the 3'-end nucleotide, compared to the position of bound dGTP
      and previously reported NRTI/dNTP. In addition, the protruding methylene group of
      bound ETV-TP directly pushes the side-chain of Met184 backward. Met184 is a key
      residue that confers ETV resistance upon substitution with smaller Ile/Val. These
      results provide novel insights into NRTI binding to the N-site and further
      provide important clues for the development of novel anti-HBV/HIV-1 RT inhibitors
      to overcome critical drug resistance.

PMID- 29374262
TI  - Measurements of growing surface tension of amorphous-amorphous interfaces on
      approaching the colloidal glass transition.
AB  - There is mounting evidence indicating that relaxation dynamics in liquids
      approaching their glass transition not only become increasingly cooperative, but
      the relaxing regions also become more compact in shape. Of the many theories of
      the glass transition, only the random first-order theory-a thermodynamic
      framework-anticipates the surface tension of relaxing regions to play a role in
      deciding both their size and morphology. However, owing to the amorphous nature
      of the relaxing regions, even the identification of their interfaces has not been
      possible in experiments hitherto. Here, we devise a method to directly quantify
      the dynamics of amorphous-amorphous interfaces in bulk supercooled colloidal
      liquids. Our procedure also helped unveil a non-monotonic evolution in dynamical
      correlations with supercooling in bulk liquids. We measure the surface tension of
      the interfaces and show that it increases rapidly across the mode-coupling area
      fraction. Our experiments support a thermodynamic origin of the glass transition.

PMID- 29374263
TI  - Ceramide Synthase 6 Deficiency Enhances Inflammation in the DSS model of Colitis.
AB  - Colitis, an inflammatory disease of the digestive tract, is increasing in
      incidence and prevalence. Intestinal inflammation can occur as a consequence of
      dysfunctions in sphingolipid metabolism. In this study we used ceramide synthase
      6 (CerS6) deficient mice, which have a reduced ability to generate long chain C16
      ceramide, to investigate the role of this enzyme in dextran sodium salt (DSS)
      induced colitis. While CerS6-deficient mice are protected from T cell mediated
      colitis, in the T cell independent DSS model lack of CerS6 resulted in a more
      rapid onset of disease symptoms. CerS6-deficient mice maintained low levels of
      C16-ceramide after DSS treatment, but the inflammatory lipid sphingosine-1
      phosphate was significantly increased in colon tissue. In the absence of CerS6,
      DSS induced more severe pathology in the colon including enhanced neutrophil
      infiltration. In vivo analysis of myeloperoxidase activity, an enzyme released
      from neutrophils, was approximately 2.5-fold higher in CerS6-deficient mice
      compared to wild type. Differences in intestinal permeability did not account for
      the increase in neutrophils. Our study suggests that lack of CerS6 expression
      differentially impacts the development of colitis, depending on the model used.

PMID- 29374264
TI  - Oxidative stress induced by Cu nutritional disorders in Citrus depends on
      nitrogen and calcium availability.
AB  - Nutritional stress caused by copper (Cu) deficiency or toxicity affects fruit
      production of citrus orchards worldwide, but this could be minimised by fine
      tuned fertilisation in the orchards. Two experiments were performed aiming to
      evaluate the photosynthetic capacity and the antioxidant enzyme activities of
      Swingle citrumelo seedlings, grown in nutrient solution (NS) with two levels of
      nitrogen (N) in the first experiment (adequate-N and high-N) and two levels of
      calcium (Ca) in the second (low-Ca and adequate-Ca). Plants were then exposed to
      various Cu levels (low, medium and high) for 15 days. Plants under Cu-toxicity
      exhibited specific effects on reactive oxygen species formation and root-to-shoot
      plant signalling. Copper absorption was greater with increased Cu concentration
      in the NS, which reduced plant biomass accumulation, gas exchange measurements,
      the activity of nitrate reductase and affected Cu partitioning between roots and
      shoots. Despite these effects, oxidative stress induced by excess-Cu was reduced
      at the highest N dose when compared to control and, on the contrary, increased
      with low-Ca supply. Therefore, a rational supply of N or Ca minimises Cu-induced
      stress damages to roots and leaves of plants, by directly enhancing the
      antioxidant system and protecting the associated antioxidative enzyme activities,
      whilst maintaining photosynthesis.

PMID- 29374265
TI  - Endoscopic non-ablative fractional laser therapy in an orthotopic colon tumour
      model.
AB  - Colorectal cancer is one of the leading causes of cancer-related deaths. Although
      several therapeutic management strategies are available at the early colon cancer
      stages, such as endoscopic mucosal or submucosal dissection, associated
      complications often include bleeding or bowel perforations. As an alternative
      approach, we investigated endoscopic non-ablative fractional laser (eNAFL)
      irradiation as a minimally invasive therapeutic modality for the treatment of
      early-stage colorectal cancer. By implanting SL4-DsRed colon cancer cells into
      the colons of the C57BL/6 mice, we developed an orthotopic colon tumour mouse
      model and demonstrated the early-stage tumour growth delay following the eNAFL
      irradiation. Additionally, we evaluated the temperature changes in the eNAFL
      irradiated area using numerical simulations, and induced inflammation using
      histological analysis. Our results indicate a minimal thermal damage confined to
      the irradiated spot, sparing the adjacent tissue and alteration in the tumour
      microenvironment. eNAFL irradiation may be clinically useful as a minimally
      invasive therapeutic intervention at the early stage of tumourigenesis. In
      future, an optimal eNAFL therapeutic dose should be determined, in order to
      increase the efficacy of this approach.

PMID- 29374266
TI  - Monoclonal and oligoclonal TCR AV and BV gene usage in CD4+ T cells from pigs
      immunised with C-strain CSFV vaccine.
AB  - The classical swine fever virus C-strain vaccine (C-strain vaccine) plays a vital
      role in preventing and controlling the spread of classical swine fever (CSF).
      However, the protective mechanisms of C-strain vaccine and cellular immunity
      conferred by T cell receptors (TCRs) are less well defined. We aimed to analyse
      the association between the complementarity determining region 3 (CDR3)
      spectratype of alphabetaTCR in CD4+ T cells and C-strain vaccine; and to find
      conserved CDR3 amino acid motifs in specific TCR alpha- and beta-chains. We found
      that the CDR3 spectratype showed dynamic changes correlating with C-strain
      vaccine immunisation and that TCR AV5S/8-3S/8-4S/14/38 and BV4S/6S/7S/15S/30 gene
      families showed clonal expansion in immunised pigs. The sequences of CDR3 from
      these clonally expanded T cells indicated a high frequency of the 'KLX' motif in
      the TCR alpha chain and the 'GGX' motif in beta chain, and Jalpha39, Jalpha43,
      Jbeta2.5 and Jbeta2.3 genes were also found in high frequency. To the best of our
      knowledge, this is the first report describing the dynamic changes of
      alphabetaTCRs and conserved CDR3 amino acid motifs in CD4+ T cells from C-strain
      vaccine-immunised pigs, which will provide a basis for the development of high
      efficiency epitope vaccines.

PMID- 29374267
TI  - Quorum-sensing control of antibiotic resistance stabilizes cooperation in
      Chromobacterium violaceum.
AB  - Many Proteobacteria use quorum sensing to regulate production of public goods,
      such as antimicrobials and proteases, that are shared among members of a
      community. Public goods are vulnerable to exploitation by cheaters, such as
      quorum sensing-defective mutants. Quorum sensing- regulated private goods, goods
      that benefit only producing cells, can prevent the emergence of cheaters under
      certain growth conditions. Previously, we developed a laboratory co-culture model
      to investigate the importance of quorum-regulated antimicrobials during
      interspecies competition. In our model, Burkholderia thailandensis and
      Chromobacterium violaceum each use quorum sensing-controlled antimicrobials to
      inhibit the other species' growth. Here, we show that C. violaceum uses quorum
      sensing to increase resistance to bactobolin, a B. thailandensis antibiotic, by
      increasing transcription of a putative antibiotic efflux pump. We demonstrate
      conditions where C. violaceum quorum-defective cheaters emerge and show that in
      these conditions, bactobolin restrains cheaters. We also demonstrate that
      bactobolin restrains quorum-defective mutants in our co-culture model, and the
      increase in antimicrobial-producing cooperators drives the C. violaceum
      population to become more competitive. Our results describe a mechanism of
      cheater restraint involving quorum control of efflux pumps and demonstrate that
      interspecies competition can reinforce cooperative behaviors by placing
      constraints on quorum sensing-defective mutants.

PMID- 29374268
TI  - The impact of failure: unsuccessful bacterial invasions steer the soil microbial
      community away from the invader's niche.
AB  - Although many environments like soils are constantly subjected to invasion by
      alien microbes, invaders usually fail to succeed, succumbing to the robust
      diversity often found in nature. So far, only successful invasions have been
      explored, and it remains unknown to what extent an unsuccessful invasion can
      impact resident communities. Here we hypothesized that unsuccessful invasions can
      cause impacts to soil functioning by decreasing the diversity and niche breadth
      of resident bacterial communities, which could cause shifts to community
      composition and niche structure-an effect that is likely exacerbated when
      diversity is compromised. To examine this question, diversity gradients of soil
      microbial communities were subjected to invasion by the frequent, yet oft
      unsuccessful soil invader, Escherichia coli, and evaluated for changes to
      diversity, bacterial community composition, niche breadth, and niche structure.
      Contrary to expectations, diversity and niche breadth increased across treatments
      upon invasion. Community composition and niche structure were also altered, with
      shifts of niche structure revealing an escape by the resident community away from
      the invader's resources. Importantly, the extent of the escape varied in response
      to the community's diversity, where less diverse communities experienced larger
      shifts. Thus, although transient and unsuccessful, the invader competed for
      resources with resident species and caused tangible impacts that modified both
      the diversity and functioning of resident communities, which can likely generate
      a legacy effect that influences future invasion attempts.

PMID- 29374269
TI  - The widespread dissemination of integrons throughout bacterial communities in a
      riverine system.
AB  - Anthropogenic inputs increase levels of antimicrobial resistance (AMR) in the
      environment, however, it is unknown how these inputs create this observed
      increase, and if anthropogenic sources impact AMR in environmental bacteria. The
      aim of this study was to characterise the role of waste water treatment plants
      (WWTPs) in the dissemination of class 1 integrons (CL1s) in the riverine
      environment. Using sample sites from upstream and downstream of a WWTP, we
      demonstrate through isolation and culture-independent analysis that WWTP effluent
      significantly increases both CL1 abundance and antibiotic resistance in the
      riverine environment. Characterisation of CL1-bearing isolates revealed that CL1s
      were distributed across a diverse range of bacteria, with identical complex
      genetic resistance determinants isolated from both human-associated and common
      environmental bacteria across connected sites. Over half of sequenced CL1s lacked
      the 3'-conserved sequence ('atypical' CL1s); surprisingly, bacteria carrying
      atypical CL1s were on average resistant to more antibiotics than bacteria
      carrying 3'-CS CL1s. Quaternary ammonium compound (QAC) resistance genes were
      observed across 75% of sequenced CL1 gene cassette arrays. Chemical data analysis
      indicated high levels of boron (a detergent marker) downstream of the WWTP.
      Subsequent phenotypic screening of CL1-bearing isolates demonstrated that ~90%
      were resistant to QAC detergents, with in vitro experiments demonstrating that
      QACs could solely select for the transfer of clinical antibiotic resistance genes
      to a naive Escherichia coli recipient. In conclusion, this study highlights the
      significant impact of WWTPs on environmental AMR, and demonstrates the widespread
      carriage of clinically important resistance determinants by environmentally
      associated bacteria.

PMID- 29374271
TI  - Reduction but no shift in brain activation after arithmetic learning in children:
      A simultaneous fNIRS-EEG study.
AB  - Neurocognitive studies of arithmetic learning in adults have revealed decreasing
      brain activation in the fronto-parietal network, along with increasing activation
      of specific cortical and subcortical areas during learning. Both changes are
      associated with a shift from procedural to retrieval strategies for problem
      solving. Here we address the critical, open question of whether similar
      neurocognitive changes are also evident in children. In this study, 20 typically
      developing children were trained to solve simple and complex multiplication
      problems. The one-session and two-week training effects were monitored using
      simultaneous functional near-infrared spectroscopy (fNIRS) and
      electroencephalography (EEG). FNIRS measurement after one session of training on
      complex multiplication problems revealed decreased activation at the left angular
      gyrus (AG), right superior parietal lobule, and right intraparietal sulcus. Two
      weeks of training led to decreased activation at the left AG and right middle
      frontal gyrus. For both simple and complex problems, we observed increased alpha
      power in EEG measurements as children worked on trained versus untrained
      problems. In line with previous multiplication training studies in adults,
      reduced activation within the fronto-parietal network was observed after
      training. Contrary to adults, we found that strategy shifts via arithmetic
      learning were not contingent on the activation of the left AG in children.

PMID- 29374270
TI  - A retrospective cohort study on the outcomes of ischemic stroke patients with
      adjuvant Korean Medicine treatment.
AB  - This study aims to examine the long-term effect of adjuvant treatment in Korean
      Medicine (KM) clinics in ischemic stroke patients, using a national sample cohort
      from the National Health Insurance Service in Korea between 2010 and 2013. The
      National Health Insurance Service - National Sample Cohort database from 2002 to
      2013 was used in this study. Ischemic stroke patients were defined and covariates
      were included to account for socioeconomic variables, comorbidities and disease
      severity. Propensity score matching was applied. Cox proportional hazards
      modeling and Kaplan-Meier analysis were applied to determine the differences
      between KM and non-KM treated groups. The results shows that KM-treated group had
      a higher probability of survival than non-KM group patients. No significant
      difference was observed between the risk of readmission between the treated and
      non-treated patients. Kaplan-Meier analysis showed a weak effect of KM treatments
      in the patients with 8 to 28 days of hospital stay for a lower risk of recurrence
      than in non-treated patients. In conclusion, KM treatment of mild to moderate
      ischemic stroke patients has a mild effect on the survival probability of stroke.
      Its effect for improving long-term recurrence need to be explored in the future
      studies.

PMID- 29374273
TI  - Resource control of epidemic spreading through a multilayer network.
AB  - While the amount of resource is an important factor in control of contagions,
      outbreaks may occur when they reach a finite fraction of the population. An
      unexplored issue is how much the resource amount is invested to control this
      outbreak. Here we analyze a mechanic model of epidemic spreading, which considers
      both resource factor and network layer. We find that there is a resource
      threshold, such that a significant fraction of the total population may be
      infected (i.e., an outbreak will occur) if the amount of resource is below this
      threshold, but the outbreak may be effectively eradicated if it is beyond the
      threshold. The threshold is dependent upon both the connection strength between
      the layers and their internal structure. We also find that the layer-layer
      connection strength can lead to the phase transition from the first-order phase
      to the continuous one or vice versa, whereas the internal connection can result
      in a different kind of phase transition (i.e., the so-called hybrid phase
      transition) apart from first-order and continuous one. Our results could have
      important implications for government decisions on public health resources
      devoted to epidemic disease control.

PMID- 29374272
TI  - Structural changes in alginate-based microspheres exposed to in vivo environment
      as revealed by confocal Raman microscopy.
AB  - A next-generation cure for type 1 diabetes relies on immunoprotection of insulin
      producing cells, which can be achieved by their encapsulation in microspheres
      made of non-covalently crosslinked hydrogels. Treatment success is directly
      related to the microsphere structure that is characterized by the localization of
      the polymers constituting the hydrogel material. However, due to the lack of a
      suitable analytical method, it is presently unknown how the microsphere structure
      changes in vivo, which complicates evaluation of different encapsulation
      approaches. Here, confocal Raman microscopy (CRM) imaging was tailored to serve
      as a powerful new tool for tracking structural changes in two major encapsulation
      designs, alginate-based microbeads and multi-component microcapsules. CRM
      analyses before implantation and after explantation from a mouse model revealed
      complete loss of the original heterogeneous structure in the alginate microbeads,
      making the intentionally high initial heterogeneity a questionable design choice.
      On the other hand, the structural heterogeneity was conserved in the
      microcapsules, which indicates that this design will better retain its
      immunoprotective properties in vivo. In another application, CRM was used for
      quantitative mapping of the alginate concentration throughout the microbead
      volume. Such data provide invaluable information about the microenvironment cells
      would encounter upon their encapsulation in alginate microbeads.

PMID- 29374274
TI  - Membrane potential synchrony of neurons in anterior cingulate cortex plays a
      pivotal role in generation of neuropathic pain.
AB  - The pathophysiology of neuropathic pain generation has not been fully
      investigated. Previous studies have primarily focused on changes in the
      properties of single neurons in the brain after nerve injury; however, little is
      known concerning the role of neuron-to-neuron connections in neuropathic pain
      pathogenesis. Synaptic transmission potentiation in anterior cingulate cortex
      (ACC) has been confirmed to be responsible for the formation of neuropathic pain.
      Thus, analysis of interneuronal connections in the ACC is an important approach
      for understanding the mechanism of neuropathic pain since it provides information
      on the potency of synaptic transmission. Here, we recorded membrane potentials
      from pairs of ACC neurons in anaesthetised rats and found that cross-correlations
      between pairs of ACC neurons significantly increased after surgery for chronic
      constriction injury (CCI). Moreover, CCI surgery could also enhance the power
      spectrum density of lower and higher-frequency membrane oscillations while having
      no effect on middle-frequency oscillations. The activation of membrane potential
      synchrony and power spectrum was reversed by the electrical synapse blocker
      mefloquine and pain behaviour was simultaneously alleviated. Our results may
      indicate that activation of membrane potential synchrony contributes to
      generation of neuropathic pain.

PMID- 29374275
TI  - Usefulness of the genetic risk score to identify phenocopies in families with
      familial hypercholesterolemia?
AB  - Familial hypercholesterolemia (FH) is caused by mutations in LDLR (low-density
      lipoprotein receptor), APOB (apolipoprotein B), PCSK9 (proprotein convertase
      subtilisin/kexin type 9), or APOE (apolipoprotein E) genes in approximately 80%
      of the cases. Polygenic forms of hypercholesterolemia may be present among
      patients clinically diagnosed with FH but with no identified mutation (FH
      mutation-negative (FH/M-)). To address whether polygenic forms may explain
      phenocopies in FH families, we calculated a 6-single-nucleotide polymorphism
      (SNP) genetic risk score (GRS) in all members from five French FH families where
      a mutation was identified (FH/M+) as well as some phenocopies (FH/M-). In two
      families, three FH/M- patients present a high GRS suggesting a polygenic
      hypercholesterolemia for these phenocopies. However, a high GRS is also observed
      in nine FH/M+ patients and in four unaffected relatives from three families.
      These observations indicate that the GRS does not seem to be a good diagnostic
      tool at the individual level. Nevertheless, the GRS seems to be a contributor of
      the severity of hypercholesterolemia since patients who cumulate a mutation and a
      high GRS exhibit higher low-density lipoprotein cholesterol levels when compared
      to patients with only FH (p = 0.054) or only polygenic hypercholesterolemia (p =
      0.0039). In conclusion, the GRS can be used as a marker of the severity of
      hypercholesterolemia but does not seem to be a reliable tool to distinguish
      phenocopies within FH families.

PMID- 29374276
TI  - Patient experience and utility of genetic information: a cross-sectional study
      among patients tested for cancer susceptibility and thrombophilia.
AB  - We evaluated whether genetic tests with evidence of clinical and personal utility
      (i.e. APC and BRCA1/2 tests) are associated with higher satisfaction and a more
      positive perception of care experience than those with undefined utility (i.e.
      tests for thrombophilia). A cross-sectional survey was performed through
      telephone interviews to patients tested for deleterious variants in APC or
      BRCA1/2 genes, or for inherited thrombophilia (FV Leiden and/or FIIG20210A)
      during a 5-year period (2008-2012). Three aspects of patient experience were
      assessed: effective communication through pre- and post-test genetic counselling;
      collaboration between caregivers on the management of patient care; and impact of
      genetic testing on quality of life. Overall 237 patients had telephone
      interviews. Multivariate logistic regression analyses showed that patients tested
      for APC or BRCA1/2 variants were more likely to be satisfied with both pre- and
      post-test counselling than those tested for inherited thrombophilia (APC vs.
      thrombophilia, p = 0.039 and 0.005; BRCA1/2 vs. thrombophilia, p = 0.030 and
      <0.001). Patients tested for APC were more likely to report an improvement in
      quality of life than those for thrombophilia (OR = 2.97, 95%CI 1.14, 7.72; p =
      0.025). A positive association was observed between patients who underwent
      BRCA1/2 testing, and self-perceived improvement in quality of life (OR = 1.41,
      95%CI 0.74, 2.69; p = 0.294). Tests of undefined clinical and personal utility
      are associated with a lower degree of patient satisfaction with genetic
      counselling and no clear opinions on changes in quality of life compared with
      those with well-defined utility.

PMID- 29374277
TI  - CXorf56, a dendritic neuronal protein, identified as a new candidate gene for X
      linked intellectual disability.
AB  - Intellectual disability (ID) comprises a large group of heterogeneous disorders,
      often without a known molecular cause. X-linked ID accounts for 5-10% of male ID
      cases. We investigated a large, three-generation family with mild ID and behavior
      problems in five males and one female, with a segregation suggestive for X-linked
      inheritance. Linkage analysis mapped a disease locus to a 7.6 Mb candidate region
      on the X-chromosome (LOD score 3.3). Whole-genome sequencing identified a 2 bp
      insertion in exon 2 of the chromosome X open reading frame 56 gene (CXorf56),
      resulting in a premature stop codon. This insertion was present in all
      intellectually impaired individuals and carrier females. Additionally, X
      inactivation status showed skewed methylation patterns favoring the inactivation
      of the mutated allele in the unaffected carrier females. We demonstrate that the
      insertion leads to nonsense-mediated decay and that CXorf56 mRNA expression is
      reduced in the impaired males and female. In murine brain slices and primary
      hippocampal neuronal cultures, CXorf56 protein was present and localized in the
      nucleus, cell soma, dendrites, and dendritic spines. Although no other families
      have been identified with pathogenic variants in CXorf56, these results suggest
      that CXorf56 is the causative gene in this family, and thus a novel candidate
      gene for X-linked ID with behavior problems.

PMID- 29374278
TI  - Birth weight and body mass index z-score in childhood brain tumors: A cross
      sectional study.
AB  - Children with brain tumors (CBT) are at higher risk of cardiovascular disease and
      type 2 diabetes compared to the general population, in which birth weight is a
      risk factor for these diseases. However, this is not known in CBT. The primary
      aim of this study was to explore the association between birth weight and body
      mass measures in CBT, compared to non-cancer controls. This is a secondary data
      analysis using cross-sectional data from the CanDECIDE study (n = 78 CBT and n =
      133 non-cancer controls). Age, sex, and birth weight (grams) were self-reported,
      and confirmed through examination of the medical records. Body mass index (BMI)
      was calculated from height and weight measures and reported as kg/m2. BMI z
      scores were obtained for subjects under the age of 20 years. Multivariable linear
      regression was used to evaluate the relationship between birth weight and BMI and
      BMI z-score, adjusted for age, sex, puberty, and fat mass percentage. Higher
      birth weight was associated with higher BMI and BMI z-score among CBT and
      controls. In conclusion, birth weight is a risk factor for higher body mass
      during childhood in CBT, and this may help the identification of children at risk
      of future obesity and cardiometabolic risk.

PMID- 29374280
TI  - Formation, Microstructure, and Conductivity of a Novel Ga2S3-Sb2S3-AgI
      Chalcogenide System.
AB  - Novel glasses in a Ga2S3-Sb2S3-AgI system were prepared with a melt-quenching
      method, and their glass-forming region was identified. The maximum dissolvable
      AgI in glasses was 65 mol%. The thermal, optical, and structural properties of
      glasses were investigated as a function of AgI and Ga2S3 contents. The Ga2S3
      Sb2S3-AgI glasses possess a wide region of transmission window (0.65-14 MUm). An
      ionic conductivity of approximately 1.01 * 10-3 S/cm can be obtained for a 40
      (0.8Sb2S3-0.2Ga2S3)-60AgI glass at an ambient temperature, and the ionic
      conductivity increased as temperature increased. The relative activation energy
      of Ag+ conduction was also calculated. These novel glasses show potential for the
      combined application of infrared optics and solid electrolytes.

PMID- 29374279
TI  - Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation
      towards Multipotency.
AB  - Recently, we reported that bacterial incorporation induces cellular
      transdifferentiation of human fibroblasts. However, the bacterium-intrinsic
      cellular- transdifferentiation factor remained unknown. Here, we found that
      cellular transdifferentiation is caused by ribosomes. Ribosomes, isolated from
      both prokaryotic and eukaryotic cells, induce the formation of embryoid body-like
      cell clusters. Numerous ribosomes are incorporated into both the cytoplasm and
      nucleus through trypsin-activated endocytosis, which leads to cell-cluster
      formation. Although ribosome-induced cell clusters (RICs) express several
      stemness markers and differentiate into derivatives of all three germ layers in
      heterogeneous cell populations, RICs fail to proliferate, alter the methylation
      states of pluripotent genes, or contribute to teratoma or chimera formation.
      However, RICs express markers of epithelial-mesenchymal transition without
      altering the cell cycle, despite their proliferation obstruction. These findings
      demonstrate that incorporation of ribosomes into host cells induces cell
      transdifferentiation and alters cellular plasticity.

PMID- 29374281
TI  - Experimentally evoked same-sex sexual behaviour in pigeons: better to be in a
      female-female pair than alone.
AB  - Same-sex sexual behaviour has been noted among social animals. However, because
      of the large number of observations necessary, data from controlled experiments
      are lacking. In this study, we performed experiments to evaluate the effects of
      male and female removal in colonies of the feral pigeon (Columba livia f.
      urbana). After the experimental removal of males, five long-lasting female-female
      pairs occurred. We found that those pairs could successfully raise offspring in a
      manner comparable to female-male pairs. Same-sex sexual behaviour and pairing in
      females is thus a better alternative to postponed breeding or breeding alone
      without the help of a partner. In contrast, in the case of female-removal
      experiments, same-sex pairing behaviour occurred in males as a temporary
      phenomenon with characteristic mutual aggression. Additionally, under a male
      biased sex ratio, we observed father-son and father-daughter copulations. To the
      best of our knowledge, these results are the first obtained under controlled
      experimental conditions which demonstrate that the sex ratio of a population can
      shift the social structure and cause cooperative same-sex breeding behaviour to
      arise in a monogamous species.

PMID- 29374282
TI  - The Altered Supramolecular Structure of Dopamine D2 Receptors in Disc1-deficient
      Mice.
AB  - Disc1 is a susceptibility gene for psychiatric disorders including schizophrenia.
      It has been suggested that excess transmission through dopamine type 2 receptors
      (D2Rs) in the striatum is an underlying mechanism of pathogenesis. In this study,
      we used super-resolution microscopy to study the distribution of D2Rs at the
      nanoscale in mice lacking exons 2 and 3 of Disc1 (Disc1-deficient mice). We found
      that D2Rs in the nucleus accumbens (NAc) of wild-type mice form nanoclusters (~
      20,000 nm2), and that Disc1-deficient mice have larger and more D2R nanoclusters
      than wild-type mice. Interestingly, administration of clozapine reduced the size
      and spatial distribution of the nanoclusters only in Disc1-deficient mice.
      Moreover, we observed that medium spiny neurons in the NAc of Disc1-deficient
      mice had reduced spine density on their dendrites than did wild-type mice, and
      this was also reversed by clozapine administration. The altered D2R nanoclusters
      might be morphological representations of the altered dopaminergic transmission
      in disease states such as schizophrenia.

PMID- 29374284
TI  - Well-Being and Resilience in Children With Speech and Language Disorders.
AB  - Purpose: Children with speech and language disorders are at risk in relation to
      psychological and social well-being. The aim of this study was to understand the
      experiences of these children from their own perspectives focusing on risks to
      their well-being and protective indicators that may promote resilience. Method:
      Eleven 9- to 12-year-old children (4 boys and 7 girls) were recruited using
      purposeful sampling. One participant presented with a speech sound disorder, 1
      presented with both a speech and language disorder, and 9 with language
      disorders. All were receiving additional educational supports. Narrative inquiry,
      a qualitative design, was employed. Data were generated in home and school
      settings using multiple semi-structured interviews with each child over a 6-month
      period. A total of 59 interviews were conducted. The data were analyzed to
      identify themes in relation to potential risk factors to well-being and
      protective strategies. Results: Potential risk factors in relation to well-being
      were communication impairment and disability, difficulties with relationships,
      and concern about academic achievement. Potential protective strategies were
      hope, agency, and positive relationships. Conclusion: This study highlights the
      importance of listening to children's narratives so that those at risk in
      relation to well-being can be identified. Conceptualization of well-being and
      resilience within an ecological framework may enable identification of protective
      strategies at both individual and environmental levels that can be strengthened
      to mitigate negative experiences.

PMID- 29374283
TI  - Measurements of AMPs in stratum corneum of atopic dermatitis and healthy skin
      tape stripping technique.
AB  - Decreased levels of antimicrobial peptides (AMPs) in atopic dermatitis (AD) have
      previously been reported and have been linked to the increased susceptibility to
      skin infections found in AD patients. This study intents to identify AMPs: hBD-2,
      hBD-3, RNase7, psoriasin and LL-37 in AD patients and healthy controls, and
      determine concentrations in consecutive depths of the outer most skin layers.
      Tape stripping was used on lesional and non-lesional skin. From each skin site,
      35 consecutive tape strips were collected and pooled in groups of 5. Commercially
      available ELISA kits were used to determine AMP concentration in stratum corneum
      samples. hBD-2, hBD-3, RNase7 and psoriasin were identified in stratum corneum
      samples. hBD-3-level was markedly higher in AD non-lesional skin compared to
      healthy controls, and a similar trend was observed for RNase7. Most AMPs were
      distributed evenly through 35 tape strips, implying a homogeneous distribution of
      antimicrobial defense in the outer most skin layers. The findings indicate that
      AD patients may not suffer from a general baseline deficiency in AMPs, and that
      the innate immune defense is present throughout the stratum corneum, both
      insights of importance for understanding the role of AMPs in AD.

PMID- 29374285
TI  - A Narrative Evaluation of Mandarin-Speaking Children With Language Impairment.
AB  - Purpose: We aimed to study narrative skills in Mandarin-speaking children with
      language impairment (LI) to compare with children with LI speaking Indo-European
      languages. Method: Eighteen Mandarin-speaking children with LI (mean age 6;2
      [years;months]) and 18 typically developing (TD) age controls told 3 stories
      elicited using the Mandarin Expressive Narrative Test (de Villiers & Liu, 2014).
      We compared macrostructure-evaluating descriptions of characters, settings,
      initiating events, internal responses,plans, actions, and consequences. We also
      studied general microstructure, including productivity, lexical diversity,
      syntactic complexity, and grammaticality. In addition, we compared the use of 6
      fine-grained microstructure elements that evaluate particular Mandarin linguistic
      features. Results: Children with LI exhibited weaknesses in 5 macrostructure
      elements, lexical diversity, syntactic complexity, and 3 Mandarin-specific, fine
      grained microstructure elements. Children with LI and TD controls demonstrated
      comparable performance on 2 macrostructure elements, productivity,
      grammaticality, and the remaining 3 fine-grained microstructure features.
      Conclusions: Similarities and differences are noted in narrative profiles of
      children with LI who speak Mandarin versus those who speak Indo-European
      languages. The results are consistent with the view that profiles of linguistic
      deficits are shaped by the ambient language. Clinical implications are discussed.

PMID- 29374287
TI  - [Liquid ecstasy intoxication : GHB is more prevalent than assumed and is
      potentially more harmful].

PMID- 29374286
TI  - Evidence of Cross-Regulation in Two Closely Related Pyruvate-Sensing Systems in
      Uropathogenic Escherichia coli.
AB  - Two-component systems (TCSs) dictate many bacterial responses to environmental
      change via the activation of a membrane-embedded sensor kinase, which has
      molecular specificity for a cognate response regulator protein. However, although
      the majority of TCSs operate through seemingly strict cognate protein-protein
      interactions, there have been several reports of TCSs that violate this classical
      model of signal transduction. Our group has recently demonstrated that some of
      these cross-interacting TCSs function in a manner that imparts a fitness
      advantage to bacterial pathogens. In this study, we describe interconnectivity
      between the metabolite-sensing TCSs YpdA/YpdB and BtsS/BtsR in uropathogenic
      Escherichia coli (UPEC). The YpdA/YpdB and BtsS/BtsR TCSs have been previously
      reported to interact in K12 E. coli, where they alter the expression of putative
      transporter genes yhjX and yjiY, respectively. These target genes are both
      upregulated in UPEC during acute and chronic murine models of urinary tract
      infection, as well as in response to pyruvate and serine added to growth media in
      vitro. Here, we show that proper regulation of yhjX in UPEC requires the presence
      of all components from both of these TCSs. By utilizing plasmid-encoded
      luciferase reporters tracking the activity of the yhjX and yjiY promoters, we
      demonstrate that deletions in one TCS substantially alter transcriptional
      activity of the opposing system's target gene. However, unlike in K12 E. coli,
      single gene deletions in the YpdA/YpdB system do not alter yjiY gene expression
      in UPEC, suggesting that niche and lifestyle-specific pressures may be selecting
      for differential cross-regulation of TCSs in pathogenic and non-pathogenic E.
      coli.

PMID- 29374288
TI  - [Quality of life and posttraumatic stress disorder after out-of-hospital cardiac
      arrest].
AB  - BACKGROUND: Survival rate after out-of-hospital cardiac arrest (OHCA) is
      increasing. However, there is a lack of data concerning long-term quality of life
      of affected patients. OBJECTIVES: This study aims to investigate the
      psychological effects of out-of-hospital cardiopulmonary resuscitation. METHODS:
      All patients who were admitted to our hospital after OHCA between 01 January 2008
      and 30 June 2015 and could be discharged in good neurological condition were
      asked to fill out the Impact of Event Scale-Revised (IES-R) and 36-Item Short
      Form Health Survey (SF-36). For statistical analysis, the mean, standard
      deviation and student's t-test were used (level of significance p < 0.05).
      RESULTS: Of 280 OHCA survivors, 56 patients (20.0%) were discharged from the
      hospital in good neurological condition. Of those, 20 patients (35.7%) were
      willing to participate in this study, among them 11 women and 9 men. Compared to
      the cohort of the German normative data, the results of the SF-36 questionnaire
      of OHCA survivors showed significantly lower values in all SF-36 subscales and
      also for the summary scores. There was no significant difference compared to
      patients with myocardial infarction. Average values of the IES-R subscales for
      intrusion and avoidance were 9.9 +/- 9.3 and 9.7 +/- 7.7, respectively, and 11.3
      +/- 7.4 for hyperarousal. Calculations indicated the suspected diagnosis of
      posttraumatic stress disorder in 2 of the 20 patients (10%). DISCUSSION: Even in
      patients who could be discharged from the hospital after OHCA in good
      neurological condition, the quality of life is significantly lower compared to
      the standard population but not compared to patients with myocardial infarction.
      The data also suggest that a relevant number of patients after OHCA is affected
      by posttraumatic stress disorder. Further research efforts on optimization of
      post-resuscitation care should not only focus on survival rates but also on
      improving quality of life.

PMID- 29374289
TI  - [Subcutaneous port site metastasis after da Vinci radical laparoscopic
      prostatectomy].

PMID- 29374290
TI  - [Potential of specialized outpatient palliative care].
AB  - Palliative care patients with incurable advanced disease suffering from complex
      symptoms can receive specialized outpatient palliative care in addition to the
      existing ambulatory care system. Qualified physicians and nurses care for
      patients and their dependents in cooperation with other professionals. In
      addition to a 24/7 on-call service for emergencies or acute crises, patients and
      their dependents are offered regular visits.

PMID- 29374291
TI  - Intracardiac echocardiography for percutaneous patent foramen ovale and atrial
      septal defect occlusion.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) plays a unique role in
      transcatheter closure of atrial septal defects (ASD) and patent foramen ovale
      (PFO). However, problems such as the need for general anesthesia, possible trauma
      from endotracheal intubation, presence of "blind spots," and occasional
      inadequate imaging of some cardiac structures have necessitated better imaging
      techniques. Our study aimed to compare the findings of TEE during the initial
      diagnostic examination with those from intracardiac echocardiography (ICE)
      acquired during the interventional procedure. METHODS: A total of 65 patients in
      whom TEE was used for the diagnosis of ASD or PFO were included. Of these, 40
      patients (61.5%) had ASD with significant left to right shunt and 25 (38.5%)
      patients had PFO associated with transient ischemic attack or stroke. ICE imaging
      was performed under local anesthesia in all patients to guide interatrial
      communication closure. RESULTS: ICE provided adequate views of the defects and
      surrounding structures during the various stages of device deployment. In eight
      patients (12.3%) an additional anatomical variation was detected. All patients
      had successful device implantation and were discharged 1 day after the procedure.
      CONCLUSION: ICE is a safe and high-quality imaging technique for guiding
      transcatheter ASD and PFO occlusion. Additionally, ICE can both facilitate device
      implantation and detect cardiac abnormalities that are not identified with TEE
      during the initial diagnostic investigation.

PMID- 29374292
TI  - Cardiac MRI for detecting left atrial/left atrial appendage thrombus in patients
      with atrial fibrillation : Meta-analysis and systematic review.
AB  - BACKGROUND: The aim of this meta-analysis was to evaluate the accuracy of cardiac
      magnetic resonance (CMR) in detecting left atrial/left atrial appendage (LA/LAA)
      thrombus and to analyze the difference between the diagnostic accuracy of various
      imaging sequences. METHODS: PubMed, Web of Science, Embase, and the Cochrane
      Library were systematically searched for studies from 2000 to 2017 that compared
      CMR with transesophageal echocardiography (TEE) in detecting LA/LAA thrombus. The
      CMR images were analyzed in four categories: (1) cine-CMR; (2) first-pass
      contrast-enhanced 3D CMR angiography (CE-MRA); (3) delayed-enhancement CMR (DE
      CMR); and (4) CMR, regardless of the magnetic resonance sequences used.
      Descriptive and quantitative information was extracted and Meta-DiSc 1.4 was used
      to perform the analysis. RESULTS: The analysis included 582 patients from seven
      publications. The pooled sensitivity, specificity, diagnostic odds ratio,
      positive likelihood ratio, negative likelihood ratio, and summary receiver
      operating characteristic of cine-CMR were 91.00%, 93.00%, 50.43, 10.04, 0.24, and
      93.93%, respectively; for CE-MRA, the values were 77.00%, 97.00%, 179.21, 51.77,
      0.30, and 97.63%, respectively; for DE-CMR, 100.00%, 99.00%, 849.70, 77.62, 0.09,
      and 99.38%, respectively; and for CMR, 80.00%, 99.00%, 187.54, 24.21, 0.17, and
      97.71%, respectively. CONCLUSION: In patients with atrial fibrillation, CMR has
      been proven to be a favorable diagnostic technique for the detection and
      assessment of LA/LAA thrombus. Among the imaging sequences evaluated, DE-CMR had
      the highest sensitivity, specificity, and diagnostic accuracy.

PMID- 29374294
TI  - Imaging of Spontaneous and Traumatic Cervical Artery Dissection : Comparison of
      Typical CT Angiographic Features.
AB  - INTRODUCTION: Cervical artery dissection (CAD) is an important etiology of
      ischemic stroke and early recognition is vital to protect patients from the major
      complication of cerebral embolization by administration of anticoagulants. The
      etiology of arterial dissections differ and can be either spontaneous or
      traumatic. Even though the historical gold standard is still catheter
      angiography, recent studies suggest a good performance of computed tomography
      angiography (CTA) for detection of CAD. We conducted this research to evaluate
      the variety and frequency of possible imaging signs of spontaneous and traumatic
      CAD and to guide neuroradiologists' decision making. METHODS: Retrospective
      review of the database of our multiple injured patients admitted to the
      Department of Trauma, Hand, and Reconstructive Surgery of the University Hospital
      Munster in Germany (a level 1 trauma center) for patients with traumatic CAD
      (tCAD) and of our stroke database (2008-2015) for patients with spontaneous CAD
      (sCAD) and CT/CTA on initial clinical work-up. All images were evaluated
      concerning specific and sensitive radiological features for dissection by two
      experienced neuroradiologists. Imaging features were compared between the two
      etiologies. RESULTS: This study included 145 patients (99 male, 46 female; 45 +/-
      18.8 years of age), consisting of 126 dissected arteries with a traumatic and 43
      with spontaneous etiology. Intimal flaps were more frequently observed after
      traumatic etiology (58.1% tCADs, 6.9% sCADs; p < 0.001); additionally,
      multivessel dissections were much more frequent in trauma patients (3 sCADs, 21
      tCADs) and only less than half (42%) of the patients with traumatic dissections
      showed cervical spine fractures. CONCLUSION: Neuroradiologists should be aware
      that intimal flaps and multivessel dissections are more common after a traumatic
      etiology. In addition, it seems important to conduct a CTA in a trauma setting,
      even if no cervical spine fracture is detected.

PMID- 29374293
TI  - Effects of the SGLT2 inhibitor ipragliflozin on various diabetic symptoms and
      progression of overt nephropathy in type 2 diabetic mice.
AB  - Diabetic nephropathy is the leading cause of end-stage renal disease and is
      associated with high-cardiovascular risk and significant morbidity and mortality.
      The recent development of sodium-glucose cotransporter (SGLT) 2 inhibitors offers
      a new antidiabetic therapy via enhanced glucose excretion; however, the
      beneficial effect of these drugs on the development of type 2 diabetic overt
      nephropathy is still largely unclear. We examined the therapeutic effects of the
      SGLT2 inhibitor ipragliflozin on various diabetic symptoms and the progression of
      nephropathy in uninephrectomized type 2 diabetic mice, which exhibit not only
      typical diabetic symptoms, such as impaired insulin secretion, glucose
      intolerance, hyperglycemia, and obesity, but also overt nephropathy with decline
      in renal function. Diabetes was induced by intraperitoneal administration of
      nicotinamide (1000 mg/kg) and streptozotocin (150 mg/kg) to uninephrectomized
      high-fat diet-fed mice. Ipragliflozin (0.1-3 mg/kg) was orally administered to
      diabetic mice once daily for 4 weeks. Repeated administration of ipragliflozin
      improved diabetic symptoms, such as hyperglycemia and insulin resistance, via an
      increase in urinary glucose excretion. In addition, ipragliflozin attenuated
      albuminuria/proteinuria and the decline in renal function, and improved renal
      injury, including glomerulosclerosis and interstitial fibrosis. Our results
      demonstrate that ipragliflozin improves various diabetic symptoms and delays
      development of diabetic nephropathy. Therefore, SGLT2 inhibitors could constitute
      a novel therapeutic target for the treatment of type 2 diabetes with overt
      nephropathy.

PMID- 29374295
TI  - Correction to: Health status of Polish children and adolescents after cancer
      treatment.
AB  - The first and family names of the authors were interchanged. The correct author
      names are now correctly presented in this article.

PMID- 29374296
TI  - Population pharmacokinetics of Rilpivirine in HIV-1-infected patients treated
      with the single-tablet regimen rilpivirine/tenofovir/emtricitabine.
AB  - PURPOSE: Rilpivirine, prescribed for the treatment of HIV infection, presents an
      important inter-individual pharmacokinetic variability. We aimed to determine
      population pharmacokinetic parameters of rilpivirine in adult HIV-infected
      patients and quantify their inter-individual variability. METHODS: We conducted a
      multicenter, retrospective, and observational study in patients treated with the
      once-daily rilpivirine/tenofovir disoproxil fumarate/emtricitabine regimen. As
      part of routine therapeutic drug monitoring, rilpivirine concentrations were
      measured by UPLC-MS/MS. Population pharmacokinetic analysis was performed using
      NONMEM software. Once the compartmental and random effects models were selected,
      covariates were tested to explain the inter-individual variability in
      pharmacokinetic parameters. The final model qualification was performed by both
      statistical and graphical methods. RESULTS: We included 379 patients, resulting
      in the analysis of 779 rilpivirine plasma concentrations. Of the observed trough
      individual plasma concentrations, 24.4% were below the 50 ng/ml minimal effective
      concentration. A one-compartment model with first-order absorption best described
      the data. The estimated fixed effect for plasma apparent clearance and
      distribution volume were 9 L/h and 321 L, respectively, resulting in a half-life
      of 25.2 h. The common inter-individual variability for both parameters was 34.1%
      at both the first and the second occasions. The inter-individual variability of
      clearance was 30.3%. CONCLUSIONS: Our results showed a terminal half-life lower
      than reported and a high proportion of patients with suboptimal rilpivirine
      concentrations, which highlights the interest of using therapeutic drug
      monitoring in clinical practice. The population analysis performed with data from
      "real-life" conditions resulted in reliable post hoc estimates of pharmacokinetic
      parameters, suitable for individualization of dosing regimen.

PMID- 29374297
TI  - [Chronic heart failure in older patients : Updated national healthcare guidelines
      on chronic heart failure from a geriatric perspective].
AB  - The incidence and prevalence of chronic heart failure (CHF) increase with age. In
      the second edition of the National Disease Management Guidelines (NVL) on CHF,
      published in August 2017, geriatric aspects are specifically addressed. The paper
      provides an overview of the recommendations by the guidelines on drug therapy,
      device therapy and operative therapy as well on the coordination of care focusing
      on older and multimorbid patients.

PMID- 29374298
TI  - [Regional differences in the development of hospitalizations : An effect of
      different demographic trends?]
AB  - Population aging and population decline in many regions of the Federal Republic
      of Germany are key elements of demographic change. In the regions concerned there
      is a rising number of older people and, simultaneously, a declining population.
      So far, the consequences of regional shrinkage and growth for inpatient care
      don't seem to have been analysed very well. This paper analyses the influence of
      population aging and declining/increasing population (demographic factors) as
      well as other, non-demographic factors on the number of hospitalizations in
      Germany and the Federal States since 2000.One result of the analysis is that
      there are major differences between the Federal States. The analysis shows, for
      example, an increase of hospitalizations in Berlin while in Saxony-Anhalt the
      number of hospitalizations declines. The increase in Berlin was the result of
      population aging and, to a lower extent, an increase in population. In Saxony
      Anhalt the declining population resulted in a decreasing number of
      hospitalizations. Population aging and non-demographic factors were not able to
      compensate this trend.Overall, the effect of demographic factors on the number of
      hospitalizations remains constant over time. Short-term changes of
      hospitalizations are due to non-demographic factors, such as epidemiological
      trends, (for example trends of incidence or prevalence), or structural changes of
      health care service (for example patients shifting between different sectors of
      health care or the introduction of new reimbursement systems).

PMID- 29374299
TI  - [Reimbursement of health apps by the German statutory health insurance].
AB  - A reimbursement category for "apps" does not exist in German statutory health
      insurance. Nevertheless different ways for reimbursement of digital health care
      products or processes exist. This article provides an overview and a description
      of the most relevant finance and reimbursement categories for apps in German
      statutory health insurance. The legal qualifications and preconditions of
      reimbursement in the context of single contracts with one health insurance fund
      will be discussed as well as collective contracts with national statutory health
      insurance funds. The benefit of a general outline appeals especially in respect
      to the numerous new players and products in the health care market. The article
      will highlight that health apps can challenge existing legal market access and
      reimbursement criteria and paths. At the same time, these criteria and paths
      exist. In terms of a learning system, they need to be met and followed.

PMID- 29374300
TI  - Head and neck cancer patient experience of a new dietitian-delivered health
      behaviour intervention: 'you know you have to eat to survive'.
AB  - PURPOSE: The aim of this study was to explore head and neck cancer (HNC) patient
      experiences of a novel dietitian delivered health behaviour intervention.
      METHODS: This study is a qualitative study which employed semi-structured
      individual interviews using open and axial coding and then final selective coding
      to organise the data. Patients with HNC who had participated in a dietitian
      delivered health behaviour intervention to reduce malnutrition were invited to
      discuss their experience of this intervention. Individual interviews were
      conducted, transcribed and analysed using grounded theory. RESULTS: Nine patients
      participated in the interviews. Four dimensions were identified in the initial
      coding process: 'information', which described patients' desire for tailored
      advice during their treatment; 'challenges of treatment experience', which
      described the difficulties related to treatment side effects; 'key messages:
      importance of eating and maintaining weight', which covered perceived integral
      messages delivered to patients by dietitians; and 'dietitian's approach'
      describing patient experiences of empathic and compassionate dietitians. Two
      overarching themes resulted from examining the connections and relationships
      between these dimensions: 'survival', a connection between eating and living; and
      'support', describing the valued working partnership between dietitian and
      patient. CONCLUSIONS: Dimensions and themes overlapped with the qualitative
      literature on HNC patient experience of treatment. However, some themes, such as
      the empowerment of a message linking eating to survival, appeared unique to this
      study. Patients found this message to be delivered in a supportive manner that
      motivated change.

PMID- 29374301
TI  - Correction to: Comparing Percutaneous Transluminal Angioplasty and Stent
      Placement for Treatment of Subclavian Arterial Occlusive Disease: A Systematic
      Review and Meta-Analysis.
AB  - The original version of this paper contained an error.

PMID- 29374302
TI  - [Durvalumab improves prognosis of stage III non-small-cell lung cancer after
      definitive chemoradiotherapy].

PMID- 29374303
TI  - Negative allosteric modulation of alpha 5-containing GABAA receptors engenders
      antidepressant-like effects and selectively prevents age-associated hyperactivity
      in tau-depositing mice.
AB  - RATIONALE: Associated with frank neuropathology, patients with Alzheimer's
      disease suffer from a host of neuropsychiatric symptoms that include depression,
      apathy, agitation, and aggression. Negative allosteric modulators (NAMs) of
      alpha5-containing GABAA receptors have been suggested to be a novel target for
      antidepressant action. We hypothesized that pharmacological modulation of this
      target would engender increased motivation in stressful environments. METHODS: We
      utilized electrophysiological recordings from Xenopus oocytes and behavioral
      measures in mice to address this hypothesis. RESULTS: In the forced-swim assay in
      mice that detects antidepressant drugs, the alpha5beta3gamma2 GABAAlpha receptor
      NAM, RY-080 produced a marked antidepressant phenotype. Another compound, PWZ
      029, was characterized as an alpha5beta3gamma2 receptor NAM of lower intrinsic
      efficacy in electrophysiological studies in Xenopus oocytes. In contrast to RY
      080, PWZ-029 was only moderately active in the forced-swim assay and the
      alpha5beta3gamma2 receptor antagonist, Xli-093, was not active at all. The
      effects of RY-080 were prevented by the non-selective benzodiazepine receptor
      antagonist flumazenil as well as by the selective ligands, PWZ-029 and Xli-093.
      These findings demonstrate that this effect of RY-080 is driven by negative
      allosteric modulation of alpha5betagamma2 GABAA receptors. RY-080 was not active
      in the tail-suspension test. We also demonstrated a reduction in the age
      dependent hyperactivity exhibited by transgenic mice that accumulate pathological
      tau (rTg4510 mice) by RY-080. The decrease in hyperactivity by RY-080 was
      selective for the hyperactivity of the rTg4510 mice since the locomotion of
      control strains of mice were not significantly affected by RY-080. CONCLUSIONS:
      alpha5betagamma2 GABAA receptor NAMs might function as a pharmacological
      treatment for mood, amotivational syndromes, and psychomotor agitation in
      patients with Alzheimer's and other neurodegenerative disorders.

PMID- 29374304
TI  - Differences in trait impulsivity do not bias the response to pharmacological drug
      challenge in the rat five-choice serial reaction time task.
AB  - RATIONALE: Maladaptive impulsivity is symptomatic of several neuropsychiatric
      disorders including schizophrenia, attention-deficit hyperactivity disorder
      (ADHD), and substance abuse disorders; paradigms designed to assess the
      underlying neurobiology of this behavior are essential for the discovery of novel
      therapeutic agents. Various models may be used to assess impulsivity as measured
      by the five-choice serial reaction time task (5-CSRTT), including variable inter
      trial interval (ITI) sessions, the selection of extreme high and low impulsivity
      phenotypes from a large outbred population of rats, as well as pharmacological
      challenges. OBJECTIVES: The aim of this study is to evaluate if pharmacological
      challenge models for impulsivity are biased by underlying differences in
      impulsivity phenotype. METHODS: Extreme high and low impulsivity phenotypes were
      selected in the 5-CSRTT, and dose-dependent effects of various pharmacological
      challenges, namely MK-801, yohimbine, and cocaine, were evaluated on task
      performance, specifically accuracy and premature responses. RESULTS: All three
      compounds increased premature responding, while a decrease in attentional
      performance occurred following MK-801 and yohimbine administration. No
      differences in drug-induced impulsivity between rats selected for high or low
      impulsivity or in parameters indicative of attentional performance could be
      determined. CONCLUSIONS: Our findings indicate that different pharmacological
      challenges increase impulsivity on the 5-CSRTT, with modest effects on attention.
      These effects were not influenced by underlying differences in impulsivity
      phenotype, which is an important prerequisite to reliably use these challenge
      models to screen and profile compounds with putative anti-impulsive
      characteristics.

PMID- 29374305
TI  - Effects of nicotine self-administration on incentive salience in male Sprague
      Dawley rats.
AB  - RATIONALE: Prolonged use of nicotine appears to enhance incentive salience, a
      motivational-cognitive process that transforms an otherwise neutral stimulus into
      a "wanted" stimulus. It has been suggested that nicotinic enhancement of
      incentive salience contributes to the potential of relapse in individuals with
      tobacco addiction. However, there are two main limitations of prior research that
      caution this claim: (a) the use of passive experimentally delivered nicotine and
      (b) the use of sign-tracking as an index of incentive salience, without
      acknowledging the competing nature of goal- and sign-tracking responses.
      OBJECTIVES: To determine whether nicotinic enhancement of incentive salience
      attributed to non-nicotinic stimuli occurs when rats self-administer nicotine,
      and whether it is facilitated by a prior history of nicotine self-administration.
      METHODS: Twenty-three male rats were trained daily, for 24 days, on a nicotine
      self-administration (SA) paradigm in the morning, and on a four-conditioned
      stimuli Pavlovian conditioned approach (4-CS PCA) task in the afternoon. Self
      administration was followed by extinction and cue reinstatement. A subcutaneous
      nicotine challenge was performed during the last 7 days of the study. RESULTS:
      Nicotine self-administration selectively enhanced sign-tracking in the 4-CS PCA.
      Upon extinction, sign-tracking quickly declined to control levels. Experimenter
      administered nicotine enhanced sign-tracking similarly regardless of nicotine
      history. CONCLUSIONS: The results suggest that nicotinic enhancement of incentive
      salience is transient, and a previous history of nicotine use does not cause
      further sensitization. Taken together, these results suggest that nicotine
      enhances incentive salience, particularly-and perhaps exclusively-while onboard.

PMID- 29374306
TI  - Intraoperative colonic pulse oximetry in left-sided colorectal surgery: can it
      predict anastomotic leak?
AB  - BACKGROUND: An anastomotic leak is a fairly common and a potentially lethal
      complication in colorectal surgery. Objective methods to assess the viability and
      blood circulation of the anastomosis could help in preventing leaks.
      Intraoperative pulse oximetry is a cheap, easy to use, fast, and readily
      available method to assess tissue viability. Our aim was to study whether
      intraoperative pulse oximetry can predict the development of an anastomotic leak.
      METHODS: The study was a prospective single-arm study conducted between the years
      2005 and 2011 in Helsinki University Hospital. Patient material consisted of 422
      patients undergoing elective left-sided colorectal surgery. The patients were
      operated by one of the three surgeons. All of the operations were partial or
      total resections of the left side of the colon with a colorectal anastomosis. The
      intraoperative colonic oxygen saturation was measured with pulse oximetry from
      the colonic wall, and the values were analyzed with respect to post-operative
      complications. RESULTS: 2.3 times more operated anastomotic leaks occurred when
      the colonic StO2 was <= 90% (11/129 vs 11/293). The mean colonic StO2 was 91.1 in
      patients who developed an operated anastomotic leak and 93.0 in patients who did
      not. With logistic regression analysis, the risk of operated anastomotic leak was
      4.2 times higher with StO2 values <= 90%. CONCLUSIONS: Low intraoperative colonic
      StO2 values are associated with the occurrence of anastomotic leak. Despite its
      handicaps, the method seems to be useful in assessing anastomotic viability.

PMID- 29374308
TI  - [Importance of laparoscopic liver resection compared to laparoscopic
      radiofrequency ablation].

PMID- 29374309
TI  - [Branch duct IPMN: resection or surveillance?]

PMID- 29374310
TI  - [Laparoscopic ileocecal resection compared with infliximab for terminal ileitis].

PMID- 29374307
TI  - Cellular populations and thermosensing mechanisms of the hypothalamic
      thermoregulatory center.
AB  - Temperature affects all aspects of life down to the diffusion rates of
      biologically active molecules and reaction rates of enzymes. The reciprocal
      argument holds true as well and every biological process down to enzymatic
      reactions influences temperature. In order to assure biological stability,
      mammalian organisms possess the remarkable ability to maintain internal body
      temperature within a narrow range, which in humans and mice is close to 37 
      degrees C, despite wide environmental temperature variations and different rates
      of internal heat production. Nevertheless, body temperature is not a static
      property but adaptively regulated upon physiological demands and in the context
      of pathological conditions. The brain region that has been primarily associated
      with internal temperature regulation is the preoptic area and the anterior
      portion of the hypothalamus. Similar to a thermostat, this brain area detects
      deep brain temperature, integrates temperature information from peripheral body
      sensors, and-based on these inputs--controls body temperature homeostasis.
      Discovered more than a century ago, we still know comparatively little about the
      molecular and cellular make-up of the hypothalamic thermoregulatory center. After
      a brief historic outline that led to the discovery of the thermoregulatory
      center, we here review recent studies that have considerably advanced our
      understanding of hypothalamic thermoregulation. We touch upon proposed mechanisms
      of intrinsic deep brain temperature detection and focus on newly identified
      hypothalamic cell populations that mediate thermoregulatory responses and that
      provide novel entry points not only to shed light on the mechanistic
      underpinnings of the thermoregulatory center but also to probe its therapeutic
      value.

PMID- 29374311
TI  - Detection of painted-over traces of blood and seminal fluid.
AB  - Dealing with a refurbished crime scene is a special challenge for forensic
      investigators. In such cases, a crime scene may not have only been cleaned in
      order to erase all traces but the walls of an indoor crime scene could also be
      painted over in order to mask traces of the crime. So far, very few publications
      have shown that painted-over traces of blood and seminal fluid can be detected
      using a forensic light source or infrared photography. To date, there have been
      no systematically executed research studies including guidelines on which
      settings to use depending on the color of the wall. Moreover, no comparative
      study has addressed the question of whether it is better to use infrared
      photography or a forensic light source to visualize painted-over bloodstains. The
      present study covers the aforementioned gaps and shows that painted-over
      bloodstains are most easily visualized by infrared photography, while traces of
      seminal fluid are most easily visualized at 440 nm in combination with a yellow
      filter-both independent of the color of the wall paint.

PMID- 29374312
TI  - [X-ray Phase Contrast : Principles, potential and advances in clinical
      translation].
AB  - More than 100 years ago Max von Laue in Munich discovered that X-rays can be
      interpreted not only as X-ray quanta in a particle picture, but also show a wave
      character. This property has been used for a long time in basic research (e.g. in
      crystallography for determining the structure of proteins), but so far has had no
      application in medical imaging. In the last 10 years, however, very impressive
      technological progress could be made in preclinical research, which also makes
      the utilization of the wave character of X-ray light possible for medical
      imaging. These novel radiography procedures, so-called phase-contrast and dark
      field imaging, have a great potential for a pronounced improvement in X-ray
      imaging and therefore, also the diagnosis of important diseases. This article
      describes the basic principles of these novel procedures, summarizes the
      preclinical research results already achieved exemplified by various organs and
      shows the potential for future clinical utilization in radiography and computed
      tomography.

PMID- 29374313
TI  - [Importance of Virchow-Robin spaces].
AB  - Virchow-Robin spaces are perivascular fluid-filled cavities that surround
      perforating arteries and veins in the brain parenchyma. As a rule in healthy
      people they are approximately 5 mm in diameter. Typical localizations are
      brainstem ganglia, mesencephalon and the white matter of the brain. Morphological
      imaging characteristics of Virchow-Robin spaces are round or tubular, smoothly
      bordered areas which are hyperintense in T2-weighted sequences. Virchow-Robin
      spaces represent a physiological structure in normal brain parenchyma. It is
      assumed that they contain interstitial fluid filled with macrophages and play an
      important role in the drainage of interstitial fluid in the direction of the
      cervical lymph system. In many diseases, such as Alzheimer's disease,
      cerebrovascular diseases and traumatic brain injuries, an association with
      Virchow-Robin spaces is assumed. In the differential diagnostics lacunar
      infarcts, cystic space-occupying lesions, low-grade malignant tumors and
      arachnoid cysts must be considered. In individual studies an association with
      frequently occurring expanded perivascular spaces in patients with arterial
      hypertension and patients with CADASIL disease was established. Rarely, Virchow
      Robin spaces are so expanded that they lead to compression of the aqueduct or the
      foramina of Monro with subsequent hydrocephalus.

PMID- 29374314
TI  - [Advanced cartilage imaging for detection of cartilage injuries and osteochondral
      lesions].
AB  - BACKGROUND: Osteochondral defects represent a main risk factor for osteoarthritis
      of the ankle. OBJECTIVES: The aim of this article is to provide an overview of
      current optimal clinical cartilage imaging techniques of the foot and ankle and
      to show typical osteochondral injuries on imaging. MATERIALS AND METHODS: A
      thorough literature search was performed and was supported by personal
      experience. RESULTS: Cartilage imaging of the foot and ankle remains challenging.
      However, advanced morphological and quantitative magnetic resonance (MR) imaging
      techniques may provide useful clinical information, for example, concerning
      cartilage repair surgery. Compared to MRI, MR arthrography (MR-A) and CT
      arthrography (CT-A) have higher sensitivity with respect to detection of
      osteochondral defects. Regarding smaller joints of the foot, mainly advanced
      osteoarthritic changes are detected on conventional radiography; only in rare
      cases, MR and CT imaging of these smaller joints is of relevance. CONCLUSIONS:
      While at the smaller joints of the foot cartilage imaging only plays a minor
      role, at the ankle joint cross-sectional cartilage imaging using CT and MRI
      becomes more and more important for clinicians due to emerging therapeutic
      options, such as different osteochondral repair techniques.

PMID- 29374315
TI  - Robotic-assisted Roux-en-Y hepaticojejunostomy after bile duct injury.
AB  - BACKGROUND: The Da Vinci Robotic Surgical System has positioned itself as a tool
      that improves the ergonomics of the surgeon, facilitating dissection in confined
      spaces and enhancing the surgeon's skills. The technical aspects for successful
      bile duct repair are well-vascularized ducts, tension-free anastomosis, and
      complete drainage of hepatic segments, and all are achievable with robotic
      assisted approach. METHODS: This was a retrospective study of our prospectively
      collected database of patients with iatrogenic bile duct injury who underwent
      robotic-assisted Roux-en-Y hepaticojejunostomy. Pre-, intra-, and short-term
      postoperative data were analyzed. RESULTS: A total of 30 consecutive patients
      were included. The median age was 46.5 years and 76.7% were female. Neo
      confluences with section of hepatic segment IV were performed in 7 patients
      (those classified as Strasberg E4). In the remaining 23, a Hepp-Couinaud
      anastomosis was built. There were no intraoperative complications, the median
      estimated blood loss was 100 mL, and the median operative time was 245 min. No
      conversion was needed. The median length of stay was 6 days and the median length
      of follow-up was 8 months. The overall morbidity rate was 23.3%. Two patients
      presented hepaticojejunostomy leak. No mortality was registered. CONCLUSION:
      Robotic surgery is feasible and can be safely performed, with acceptable short
      term results, in bile duct injury repair providing the advantages of minimally
      invasive surgery. Further studies with larger number of cases and longer follow
      up are needed to establish the role of robotic assisted approaches in the
      reconstruction of BDI.

PMID- 29374316
TI  - Pediatric acute kidney injury and the subsequent risk for chronic kidney disease:
      is there cause for alarm?
AB  - Acute kidney injury (AKI) is characterized clinically as an abrupt decline in
      renal function marked by reduced excretion of waste products, disordered
      electrolytes, and disrupted fluid homeostasis. The recent development of a
      standardized AKI definition has transformed our understanding of AKI epidemiology
      and outcomes. We now know that in the short term, children with AKI experience
      greater morbidity and mortality; additionally, observational studies have
      established that chronic renal sequelae are far more common after AKI events than
      previously realized. Many of these studies suggest that patients who develop AKI
      are at greater risk for the subsequent development of chronic kidney disease
      (CKD). The goal of this review is to critically evaluate the data regarding the
      association between AKI and CKD in children. Additionally, we describe best
      practice approaches for future studies, including the use of consensus AKI
      criteria, the application of rigorous definitions for CKD and renal sequelae, and
      the inclusion of non-AKI comparator groups. Finally, based upon existing data, we
      suggest an archetypal approach to follow-up care for the AKI survivors who may be
      at greater CKD risk, including children with more severe AKI, those who endure
      repeated AKI episodes, patients who do not experience full recovery, and those
      with pre-existing CKD.

PMID- 29374317
TI  - Thymoma-associated multiorgan autoimmunity with exclusive gastrointestinal tract
      involvement: case report and review of the literature.
AB  - Thymoma-associated multiorgan autoimmunity (TAMA) is a recently delineated and
      rare paraneoplastic syndrome reported in patients with thymoma. The disorder is
      characterized by graft-versus-host disease-like pathology affecting the skin,
      gastrointestinal tract (GIT), and liver, and is usually associated with a poor
      outcome. We document a case of TAMA with exclusive GIT involvement which included
      the stomach, small and large bowel, presenting in a 66-year-old male patient 5
      years after complete resection of a type B2 thymoma. A brief review is provided
      of this scarce syndrome, the GIT pathology described in the 21 TAMA cases
      reported to date, and the unique characteristics of patients with exclusive GIT
      involvement by this acquired autoimmune disorder.

PMID- 29374320
TI  - Peritoneal and pleural fluids may appear hyperintense on hepatobiliary phase
      using hepatobiliary MR contrast agents.
AB  - AIM: To describe the effect of hepatobiliary-specific MR imaging contrast agent
      (HBCA) administration on the signal intensity of peritoneal and pleural fluid
      effusions on T1-weighted MR images. MATERIALS AND METHODS: From October 2015 to
      May 2016 139 patients (mean 60+/-10 years old, 69 % males) with peritoneal or
      pleural effusions without biliary leakage who underwent HBCA-MRI (Gd-BOPTA or Gd
      EOB-DTPA) at 1.5T and 3T were included from two centres. The fluid signal
      intensity was classified as hypo/iso/hyperintense before/after HBCA
      administration. The relative signal enhancement (RE) was calculated. RESULTS: On
      hepatobiliary phase (HBP), peritoneal fluids appeared hyper/isointense in 88-100
      % and pleural effusions in 100 % of the patients following Gd-BOPTA
      administration. All fluids remained hypointense following Gd-EOB-DTPA. The signal
      intensity of fluids increased with both HBCA but RE was significantly higher
      following Gd-BOPTA (p=0.002 to <0.001). RE was correlated with HBP acquisition
      time-point (r=0.42, p<0.001 and r=0.50, p=0.033 for peritoneal and pleural
      fluids). CONCLUSION: The signal intensity of pleural and peritoneal fluids
      progressively increases following HBCA administration in the absence of biliary
      leakage. Due to its later hepatobiliary phase, this is more pronounced after Gd
      BOPTA injection, leading to fluid hyperintensity that is not observed after Gd
      EOB-DTPA injection. KEY POINTS: * Fluids appear hyper/isointense on HBP in most
      patients after Gd-BOPTA injection. * Fluids remain hypointense on HBP after Gd
      EOB-DTPA injection. * RE of fluids increases with time after liver-specific Gd
      injection. * RE of fluids is higher in patients with chronic liver disease.

PMID- 29374318
TI  - Multicenter validation of cancer gene panel-based next-generation sequencing for
      translational research and molecular diagnostics.
AB  - The simultaneous detection of multiple somatic mutations in the context of
      molecular diagnostics of cancer is frequently performed by means of amplicon
      based targeted next-generation sequencing (NGS). However, only few studies are
      available comparing multicenter testing of different NGS platforms and gene
      panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK)
      performed a multicenter interlaboratory trial for targeted NGS using the same
      formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre
      characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon
      carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed
      information regarding pre-characterized mutations was not disclosed to the
      partners. Commercially available and custom-designed cancer gene panels were used
      for library preparation and subsequent sequencing on several devices of two NGS
      different platforms. For every case, centrally extracted DNA and FFPE tissue
      sections for local processing were delivered to each partner site to be sequenced
      with the commercial gene panel and local bioinformatics. For cancer-specific
      panel-based sequencing, only centrally extracted DNA was analyzed at seven
      sequencing sites. Subsequently, local data were compiled and bioinformatics was
      performed centrally. We were able to demonstrate that all pre-characterized
      mutations were re-identified correctly, irrespective of NGS platform or gene
      panel used. However, locally processed FFPE tissue sections disclosed that the
      DNA extraction method can affect the detection of mutations with a trend in favor
      of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a
      very robust method for simultaneous detection of various mutations in FFPE tissue
      specimens if certain pre-analytical conditions are carefully considered.

PMID- 29374321
TI  - Multiparametric MRI as a potential surrogate endpoint for decision-making in
      early treatment response following concurrent chemoradiotherapy in patients with
      newly diagnosed glioblastoma: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the value of multiparametric MRI for determination of
      early treatment response following concurrent chemoradiotherapy in patients with
      newly diagnosed glioblastoma. METHODS: A computerized search of Ovid-MEDLINE and
      EMBASE up to 1 October 2017 was performed to find studies on the diagnostic
      performance of multiparametric MRI for differentiating true progression from
      pseudoprogression. The beginning search date was not specified. Pooled estimates
      of sensitivity and specificity were obtained using hierarchical logistic
      regression modeling. We performed meta-regression and sensitivity analyses to
      explain the effects of the study heterogeneity. RESULTS: Nine studies including
      456 patients were included. Pooled sensitivity and specificity were 84 % (95 % CI
      74-91) and 95 % (95 % CI 83-99), respectively. Area under the hierarchical
      summary receiver operating characteristic curve was 0.95 (95 % CI 0.92-0.96).
      Meta-regression showed true progression in the study population, the mean age and
      the reference standard were significant factors affecting heterogeneity.
      CONCLUSION: Multiparametric MRI may be used as a potential surrogate endpoint for
      assessment of early treatment response, especially in the differentiation of true
      progression from pseudoprogression. However, based on the current evidence,
      monoparametric and multiparametric MRI perform equally in the clinical context.
      Further evaluation will be needed. KEY POINTS: * Multiparametric MRI shows high
      diagnostic performance for early treatment response in glioblastoma. *
      Multiparametric MRI could differentiate true progression from pseudoprogression
      in newly diagnosed glioblastoma. * The normalized rCBV derived from DSC was the
      most commonly used parameter.

PMID- 29374322
TI  - Diagnosis of breast cancer based on microcalcifications using grating-based phase
      contrast CT.
AB  - OBJECTIVES: Microcalcifications are an important feature in the diagnosis of
      breast cancer, especially in the early stages. In this paper, a CT-based method
      is proposed to potentially distinguish benign and malignant breast diseases based
      on the distributions of microcalcifications using grating-based phase-contrast
      imaging on a conventional X-ray tube. METHODS: The method presented based on the
      ratio of dark-field signals to attenuation signals in CT images is compared with
      the existing method based on the ratio in projections, and the threshold for the
      classification of microcalcifications in the two types of breast diseases is
      obtained using our approach. The experiment was operated on paraffin-fixed
      specimens that originated from 20 female patients ranging from 27-65 years old.
      RESULTS: Compared with the method based on projection images (AUC = 0.87), the
      proposed method is more effective (AUC = 0.95) to distinguish the two types of
      diseases. The discrimination threshold of microcalcifications for the
      classification of diseases in CT images is found to be 3.78 based on the Youden
      index. CONCLUSIONS: The proposed method can be further developed to improve the
      early diagnosis and diagnostic accuracy and reduce the clinical misdiagnosis rate
      of breast cancer. KEY POINTS: * Microcalcifications are of special importance to
      indicate early breast cancer. * Grating-based phase-contrast imaging can improve
      the diagnosis of breast cancers. * The method described here can better classify
      benign and malignant breast diseases.

PMID- 29374323
TI  - Trans-suppression of defense DEFB1 gene in intestinal epithelial cells following
      Cryptosporidium parvum infection is associated with host delivery of parasite
      Cdg7_FLc_1000 RNA.
AB  - To counteract host immunity, Cryptosporidium parvum has evolved multiple
      strategies to suppress host antimicrobial defense. One such strategy is to reduce
      the production of the antimicrobial peptide beta-defensin 1 (DEFB1) by host
      epithelial cells but the underlying mechanisms remain unclear. Recent studies
      demonstrate that a panel of parasite RNA transcripts of low protein-coding
      potential are delivered into infected host cells and may modulate host gene
      transcription. Using in vitro models of intestinal cryptosporidiosis, in this
      study, we analyzed the expression profile of host beta-defensin genes in host
      cells following infection. We found that C. parvum infection caused a significant
      downregulation of the DEFB1 gene. Interestingly, downregulation of DEFB1 gene was
      associated with host delivery of Cdg7_FLc_1000 RNA transcript, a C. parvum RNA
      that has previously demonstrated to be delivered into the nuclei of infected host
      cells. Knockdown of Cdg7_FLc_1000 in host cells could attenuate the trans
      suppression of host DEFB1 gene and decreased the parasite burden. Therefore, our
      data suggest that trans-suppression of DEFB1 gene in intestinal epithelial cells
      following C. parvum infection involves host delivery of parasite Cdg7_FLc_1000
      RNA, a process that may be relevant to the epithelial defense evasion by C.
      parvum at the early stage of infection.

PMID- 29374324
TI  - First report of a naturally patent infection with Dirofilaria immitis in an otter
      (Lutra lutra).
AB  - Dirofilaria immitis causes a severe and life-threatening cardio-pulmonary disease
      in Europe, Asia, Africa, and the Americas; also, zoonotic infections have been
      reported. This parasitic vector-borne disease is mostly common in domestic and
      wild canids and felids. Here, we present a rare finding of this roundworm in the
      heart of a Eurasian otter (Lutra lutra). Four mature specimens of D. immitis were
      found in the right ventricle of the heart. Necropsy was performed after the
      animal was found road-killed in Eastern Serbia, close to the Danube River. Two
      heartworms were females, one was male and sex for one remained unidentified.
      Microfilariae were present in the uterus of one of the female heartworms,
      indicating that otters can act as reservoirs of dirofilariasis in the wild. This
      is the first report of a patent infection in a free-ranging otter.

PMID- 29374326
TI  - Investigating the bone mineral density in children with solid tumors in southern
      Iran: a case-control study.
AB  - : Along with increasing childhood cancer survival, there is increasing concern
      about its chronic complications. We showed that 20.5 and 45.9% of children with
      solid tumors in southern Iran had low bone mass for chronological age in lumbar
      and femoral area, which was associated with serum ferritin and hemoglobin. 52.4%
      of these children had vitamin D deficiency, as well. PURPOSE/INTRODUCTION: Along
      with increasing the childhood cancer survival, there is increasing concern about
      the chronic complications of the disease and the related therapies. This study
      aims to compare the vitamin D status and bone mineral apparent density (BMAD) of
      these children with healthy ones and assess some possible associated factors.
      METHOD: This case-control study enrolled 50 children with solid tumors and their
      age- and sex-matched controls. Dual-energy X-ray absorptiometry was used to
      assess bone mineral density. Body mass index, puberty, physical activity, sun
      exposure, and biochemical data were assessed. RESULTS: 52.4% of children with
      solid tumors had vitamin D deficiency, and there was no significant difference
      between the prevalence of vitamin D deficiency in patients and controls (P =
      0.285). The prevalence of low bone mass for chronological age in lumbar area was
      20.5 and 12.5% in patients and controls, respectively (P = 0.399). Lumbar spine
      BMD was associated with hemoglobin level (r = 0.468, P = 0.049), while low bone
      mass in femoral neck was associated with serum ferritin (859 +/- 1037 in low bone
      mass vs. 178 +/- 264 in without low bone mass, P = 0.039). CONCLUSION: Vitamin D
      deficiency and low bone mass are prevalent among Iranian children with solid
      tumors. Future studies are warranted to investigate the best strategies to
      prevent and treat vitamin D deficiency and low bone mass in children surviving
      cancer.

PMID- 29374325
TI  - Treating Hallucinations and Delusions Associated With Parkinson's Disease
      Psychosis.
AB  - PURPOSE OF REVIEW: We discuss features of Parkinson's disease psychosis (PDP)
      including symptomology and pathophysiology. Treatment options, including non
      pharmacologic strategies, dose reduction of offending agents, and the addition of
      non-dopaminergic antipsychotics, are addressed. The efficacy of second-generation
      antipsychotics and novel agents is examined. RECENT FINDINGS: Pimavanserin, a 5
      HT2A/C receptor inverse agonist with no other receptor activity, has shown
      efficacy and tolerability and is now FDA approved for PDP treatment. Research
      into novel targets is ongoing. PDP is a morbid complication of Parkinson's
      disease with complex incompletely understood mechanisms. Treatment is directed
      towards mitigation of psychosis without worsening of motor features.

PMID- 29374327
TI  - Tranexamic acid as a local hemostasis method after dental extraction in patients
      on warfarin: a randomized controlled clinical study.
AB  - OBJECTIVES: The present work is a controlled, blinded, and randomized clinical
      trial comparing hemostatic measures for the control of post-tooth extraction
      hemorrhage in patients on anticoagulation therapy with warfarin. MATERIALS AND
      METHODS: The sample consisted of 37 patients (37.8% male and 62.2% female) with a
      mean age of 45.5 years. After randomization, 20 patients were allocated to the
      control group (conventional hemostasis measures) and 17 to the study group
      (addition of local tranexamic acid). All variables that could influence the
      outcome were similar between the groups and no significant difference was seen (p
      > 0.05). RESULTS: In the assessment of immediate hemostasis, for the control
      group, the time to achieve cessation of bleeding was 9.1 (+/- 3.6) minutes. For
      the study group this was much lower, and this difference (6.018 / confidence
      interval of 95%, 4.677 to 7.359) was statistically significant (p < 0.001). In
      evaluating the control of intermediate hemorrhage, the use of tranexamic acid was
      more significantly associated with the absence of bleeding, especially in the
      first 24 h. CONCLUSIONS AND CLINICAL RELEVANCE: Thus, this measure of local
      hemostasis in topical form with gauze compression and irrigation was shown to be
      more effective in reducing the time to attain immediate hemostasis, and in
      preventing intermediate hemorrhage.

PMID- 29374328
TI  - Possible effect of SNAIL family transcriptional repressor 1 polymorphisms in non
      syndromic cleft lip with or without cleft palate.
AB  - OBJECTIVE: Orofacial development is a complex process subjected to failure
      impairing. Indeed, the cleft of the lip and/or of the palate is among the most
      frequent inborn malformations. The JARID2 gene has been suggested to be involved
      in non-syndromic cleft lip with or without cleft palate (nsCL/P) etiology. JARID2
      interacts with the polycomb repressive complex 2 (PRC2) in regulating the
      expression patterns of developmental genes by modifying the chromatin state.
      MATERIALS AND METHODS: Genes coding for the PRC2 components, as well as other
      genes active in cell differentiation and embryonic development, were selected for
      a family-based association study to verify their involvement in nsCL/P. A total
      of 632 families from Italy and Asia participated to the study. RESULTS: Evidence
      of allelic association was found with polymorphisms of SNAI1; in particular, the
      rs16995010-G allele was undertransmitted to the nsCL/P cases [P = 0.004, odds
      ratio = 0.69 (95% C.I. 0.54-0.89)]. However, the adjusted significance value
      corrected for all the performed tests was P = 0.051. CONCLUSIONS: The findings
      emerging by the present study suggest for the first time an involvement of SNAI1
      in the nsCL/P onset. CLINICAL RELEVANCE: Interestingly, SNAI1 is known to promote
      epithelial to mesenchymal transition by repressing E-cadherin expression, but it
      needs an intact PRC2 to act this function. Alterations of this process could
      contribute to the complex etiology of nsCL/P.

PMID- 29374329
TI  - Using electrical resistivity tomography to assess the effectiveness of managed
      aquifer recharge in a salinized coastal aquifer.
AB  - Over 40 years, the detrital aquifer of the Plana de Castellon (Spanish
      Mediterranean coast) has been subjected to seawater intrusion because of long dry
      periods combined with intensive groundwater exploitation. Against this backdrop,
      a managed artificial recharge (MAR) scheme was implemented to improve the
      groundwater quality. The large difference between the electrical conductivity
      (EC) of the ambient groundwater (brackish water due to marine intrusion) and the
      recharge water (freshwater) meant that there was a strong contrast between the
      resistivities of the brackish water saturated zone and the freshwater saturated
      zone. Electrical resistivity tomography (ERT) can be used for surveying similar
      settings to evaluate the effectiveness of artificial recharge schemes. By
      integrating geophysical data with lithological information, EC logs from
      boreholes, and hydrochemical data, we can interpret electrical resistivity (ER)
      with groundwater EC values and so identify freshwater saturated zones. Using this
      approach, ERT images provided a high-resolution spatial characterization and an
      accurate picture of the shape and extent of the recharge plume of the MAR site.
      After 5 months of injection, a freshwater plume with an EC of 400-600 MUS/cm had
      formed that extended 400 m in the W-E direction, 250 m in the N-S direction, and
      to a depth of 40 m below piezometric level. This study also provides correlations
      between ER values with different lithologies and groundwater EC values that can
      be used to support other studies.

PMID- 29374330
TI  - Osmotic pressure between arbitrarily charged planar surfaces: A revisited
      approach.
AB  - The properties of ionic solutions between charged surfaces are often studied
      within the Poisson-Boltzmann framework, by finding the electrostatic potential
      profile. For example, the osmotic pressure between two charged planar surfaces
      can be evaluated by solving coupled equations for the electrostatic potential and
      osmotic pressure. Such a solution relies on symmetry arguments and is restricted
      to either equally or oppositely charged surfaces. Here, we provide a different
      and more efficient scheme to derive the osmotic pressure straightforwardly,
      without the need to find the electrostatic potential profile. We derive
      analytical expressions for the osmotic pressure in terms of the inter-surface
      separation, salt concentration, and arbitrary boundary conditions. Such results
      should be useful in force measurement setups, where the force is measured between
      two differently prepared surfaces, or between two surfaces held at a fixed
      potential difference. The proposed method can be systematically used for
      generalized Poisson-Boltzmann theories in planar geometries, as is demonstrated
      for the sterically modified Poisson-Boltzmann theory.

PMID- 29374331
TI  - Pressure pain thresholds over the cranio-cervical region in headache: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Sensitivity of tissues can be measured by algometry. Decreased
      pressure pain thresholds over the cranio-cervical area are supposed to reflect
      signs of sensitization of the trigemino-cervical nucleus caudalis. A systematic
      review was conducted to assess the current scientific literature describing
      pressure pain threshold (PPT) values over the cranio-cervical region in patients
      with migraine, tension-type headache (TTH), and cervicogenic headache (CeH). A
      literature search was executed in three databases. The search strategy included
      the following keywords: migraine, TTH, CeH, PPT and algometry. A total of 624
      papers was identified of which relevant papers were subsequently assessed for
      methodological quality. Twenty-two selected papers were assessed by two
      independent reviewers and the majority of studies scored low risk of bias on the
      selected items. Mean PPT values of several sites measured in the cranio-cervical
      region in patients with migraine, chronic TTH and CeH scored lower values
      compared to controls. The trapezius muscle (midpoint between vertebrae C7 and
      acromion) was the most frequently targeted site and showed significantly lower
      PPT values in adults with migraine (pooled standardized mean difference kPa: 1.26
      [95%CI -1.71, -0.81]) and chronic TTH (pooled standardized mean difference kPa: 
      2.00 [95%CI -2.93, -1.08]). Most studies found no association between PPT values
      and headache characteristics such as frequency, duration or intensity. Further
      standardization of PPT measurement in the cranio-cervical region is recommended.

PMID- 29374332
TI  - Frequency and Impact of Adverse Events in Inpatients: A Nationwide Analysis of
      Episodes between 2000 and 2015.
AB  - Despite being a potential cause of morbidity and economic costs, adverse events
      remain insufficiently studied. Therefore, we aimed to assess the frequency and
      impact of adverse events among inpatients. We analysed an administrative database
      containing a registration of all hospitalisations occurring in Portuguese public
      hospitals between 2000 and 2015. We identified all episodes with a registration
      of adverse events, and classified them into three categories, namely (1)
      misadventures of surgical and medical care, (2) complications of surgical or
      medical procedures, and (3) adverse drug events (including adverse drug
      reactions, poisoning events, and late effects). These episodes were compared over
      their length of stay, in-hospital mortality, and hospital costs with an equal
      number of hospitalisations matched for patients' and episodes' characteristics.
      Between 2000 and 2015, 5.8% (n = 861,372) of all Portuguese hospitalisations had
      a registration of at least one adverse event. Hospitalisations with registration
      of adverse events had a median length of stay of 8 days, median hospitalisation
      costs of 3060.7 Euro, and an in-hospital mortality of 6.7%. Hospitalisations with
      registration of misadventures of care, complications of procedures and adverse
      drug reactions had significantly higher lengths of stay and hospitalisation costs
      than their matched controls. In-hospital mortality was significantly higher for
      episodes of misadventures of care and complications of procedures, but lower for
      adverse drug events hospitalisations. Therefore, adverse events are common among
      inpatients, and have an important clinical and economic impact. Administrative
      databases may be useful in their epidemiological assessment.

PMID- 29374333
TI  - Energy Spectrum CT Image Detection Based Dimensionality Reduction with Phase
      Congruency.
AB  - The image feature detection is widely used in image registration, image stitching
      and object recognition. The feature detection algorithm can be applied to the
      detection of artificial images, and can be used to detect the energy spectrum CT
      image. A new algorithm of phase consistency detection based on dimensionality
      reduction is proposed in this paper. We mainly focus on the phase congruency of
      the spectral CT images in the paper and try to use dimensionality reduction to
      integrate the information of phase congruency detected in the image. The
      experimental results show that the algorithm can detect the energy spectrum CT
      image with clear edge and contour, which is beneficial to the subsequent
      processing. Meanwhile, the algorithm presented is more effective in diagnosis of
      disease for medical professionals.

PMID- 29374334
TI  - Correction to: Spatial and temporal distribution of carbon dioxide gas using
      GOSAT data over IRAN.
AB  - The original version of this article unfortunately contained an error in the
      affiliation section.

PMID- 29374335
TI  - Renal sympathetic nerve activity after catheter-based renal denervation.
AB  - BACKGROUND: Catheter-based renal sympathetic denervation (RDN) has been
      considered a potential treatment for therapy resistant hypertension (RHT).
      However, in a randomized placebo-controlled trial, RDN did not lead to a
      substantial blood pressure (BP) reduction. We hypothesized that variation in the
      reported RDN efficacy might be explained by incomplete nerve disruption as
      assessed by renal 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy.
      METHODS: In 21 RHT patients (median age 60 years), we performed 123I-mIBG
      scintigraphy before and 6 weeks after RDN. Additionally, we assessed changes in
      BP (24 h day, night, and average), plasma- and urinary-catecholamines and plasma
      renin activity (PRA) before and after RDN. Planar scintigraphy was performed at
      15 min and 4 h after 123I-mIBG administration. The ratio of the mean renal
      (specific) counts vs. muscle (non-specific) counts represented 123I-mIBG uptake.
      Renal 123I-mIBG washout was calculated between 15 min and 4 h. RESULTS: After RDN
      office-based systolic BP decreased from 172 to 153 mmHg (p = 0.036), while
      diastolic office BP (p = 0.531), mean 24 h systolic and diastolic BP (p = 0.602,
      p = 0.369, respectively), PRA (p = 0.409) and plasma catecholamines (p = 0.324)
      did not significantly change post-RDN. Following RDN, 123I-mIBG renal uptake at
      15 min was 3.47 (IQR 2.26-5.53) compared to 3.08 (IQR 2.79-4.95) before RDN (p =
      0.289). Renal 123I-mIBG washout did not change post-RDN (p = 0.230). In addition,
      there was no significant correlation between the number of denervations and the
      renal 123I-mIBG parameters. CONCLUSIONS: No changes were observed in renal 123I
      mIBG uptake or washout at 6 weeks post-RDN. These observations support incomplete
      renal denervation as a possible explanation for the lack of RDN efficacy.

PMID- 29374336
TI  - Characterization of a Whole-Cell Biotransformation Using a Constitutive Lysine
      Decarboxylase from Escherichia coli for the High-Level Production of Cadaverine
      from Industrial Grade L-Lysine.
AB  - Cadaverine is used for the synthesis of the novel bio-polyamides 54, 56, and 510.
      Here, we examine the feasibility of using a lysine decarboxylase (LdcC) from
      Escherichia coli for high-level production of cadaverine. After sequential
      optimization of whole-cell biotransformation conditions, recombinant E. coli
      overexpressing LdcC (EcLdcC) could produce 1.0 M cadaverine from 1.2 M crude L
      lysine solution after 9 h. EcLdcC retained a higher cadaverine yield after being
      reused 10 times at acidic and alkaline pH values than that of a recombinant E.
      coli strain overexpressing an inducible lysine decarboxylase (CadA), a
      conventional cadaverine producer (90 vs. 51% at pH 6 and 55 vs. 15% at pH 8).
      This study reveals that EcLdcC is a promising whole-cell biocatalyst for the bio
      based production of cadaverine from industrial grade L-lysine in comparison to
      EcCadA.

PMID- 29374338
TI  - Intraductal Papillary Neoplasm of the Bile Duct (IPNB): Case Report and
      Literature Review of a Challenging Disease to Diagnose.

PMID- 29374339
TI  - Differential expression of FOXO1 during development and myoblast differentiation
      of Qinchuan cattle and its association analysis with growth traits.
AB  - Our previous work reported a relationship between FOXO1 mutations and growth of
      Qinchuan (QC) cattle. Here, we performed differential expression analysis of
      FOXO1 and its association analysis with growth traits in QC cattle. First, we
      measured the expression of the FOXO1 gene in nine tissues during three
      developmental stages. The results showed that FOXO1 was abundantly expressed in
      tissues of calves but was strongly repressed in adulthood, although there was
      significant transcription in skeletal muscle. FOXO1 expression showed gradual up
      regulation during differentiation of primary bovine skeletal muscle cells. We
      also identified six SNPs of the bovine FOXO1 gene by sequencing DNA pools of
      samples from 488 individuals, and association analysis indicated that five SNPs
      were significantly associated with some growth traits in the QC population. We
      further analyzed four haplotype combinations of the six SNPs and found
      significant correlation with body length (P<0.01). In conclusion, FOXO1
      participates in bovine myocyte differentiation and expression, and may be a
      strong candidate as a gene that affects growth traits that could be exploited in
      a QC cattle breeding program. More generally, our data provide a new theoretical
      basis for QC beef breeding and beef quality improvement.

PMID- 29374337
TI  - Lipidomics unveils the complexity of the lipidome in metabolic diseases.
AB  - Dysregulation of lipid metabolism is responsible for pathologies of human
      diseases including metabolic diseases. Recent advances in lipidomics analysis
      allow for the targeted and untargeted identification of lipid species and for
      their quantification in normal and diseased conditions. Herein, this review
      provides a brief introduction to lipidomics, highlights its application to
      characterize the lipidome at the cellular and physiological levels under
      different biological conditions, and discusses the potential for the use of
      lipidomics in the discovery of biomarkers.

PMID- 29374340
TI  - Illness-death model: statistical perspective and differential equations.
AB  - The aim of this work is to relate the theory of stochastic processes with the
      differential equations associated with multistate (compartment) models. We show
      that the Kolmogorov Forward Differential Equations can be used to derive a
      relation between the prevalence and the transition rates in the illness-death
      model. Then, we prove mathematical well-definedness and epidemiological
      meaningfulness of the prevalence of the disease. As an application, we derive the
      incidence of diabetes from a series of cross-sections.

PMID- 29374341
TI  - Late-onset cobalamin C deficiency Chinese sibling patients with neuropsychiatric
      presentations.
AB  - The Cobalamin C deficiency (cblC), characterized with elevated methylmalonic
      acidemia and homocystinuria in plasma, is an inborn error of cobalamin
      metabolism. The late-onset cblC siblings patients were rarely reported. In this
      study, we analyzed the clinical presentations and treatment outcomes of late
      onset cblC in Chinese sibling patients with neuropsychiatric presentations. The
      clinical data of four pairs of Chinese patients were retrospectively analyzed.
      Serum homocysteine, urine organic acids measurements, neuroimaging exams and gene
      analysis were carried out in all patents. Patients were reevaluated after
      treatments with cobalamin, folate, betaine, L-carnitine and compound vitamin B.
      The mean age at disease onset was 13.7 (range 2-19) years. The neuropsychiatric
      disturbances including cognitive decline (3/8), psychiatric disturbances (4/8),
      gait instability (2/8), lower extremity weakness and numbness (3/8) and
      thromboembolic events (1/8). Two patients suffered nephropathy. The mean serum
      homocysteine when patients were diagnosed was 109.4 (range 69.5-138) MUM/L. The
      abnormal radioimaging included scoliosis by X-ray (5/6), cerebral atrophy (4/6)
      and spinal cord atrophy (3/6) by MRI scan. Three pairs of siblings showed
      heterozygous mutations of MMACHC gene including c.482G > A (4/6), c.354G > C
      (2/6), c.570insT (2/6), c.445_446del (2/6) and c.656_4658del (2/6). The other two
      siblings showed homozygous mutation with c.452A > G in MMACHC gene. After
      treatments, the psychiatric symptoms were obviously relieved in all the patients.
      In Chinese siblings with late-onset cblC, the main clinic manifestation and
      abnormal radioimaging were cognitive decline and cerebral atrophy respectively.
      The most common gene mutation was c.482G > A of MMACHC gene. The patients
      responded well to the treatments.

PMID- 29374343
TI  - Preliminary Results that Assess Metformin Treatment in a Preclinical Model of
      Pancreatic Cancer Using Simultaneous [18F]FDG PET and acidoCEST MRI.
AB  - PURPOSE: We sought to determine if the synergy between evaluations of glucose
      uptake in tumors and extracellular tumor acidosis measured with simultaneous
      positron emission tomography (PET)/magnetic resonance imaging (MRI) can improve
      longitudinal evaluations of the response to metformin treatment. PROCEDURES: A
      standard 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET protocol that evaluates
      glucose uptake in tumors, and a standard acidoCEST MRI protocol that measures
      extracellular pH (pHe) in tumors, were simultaneously performed to assess eight
      vehicle-treated (control) mice and eight metformin-treated mice 1 day before
      treatment, 1 day after initiating daily treatment with metformin, and 7 days
      after initiating treatment. Longitudinal changes in SUVmax and extracellular pH
      (pHe) were evaluated for each treatment group, and differences in SUVmax and pHe
      between metformin-treated and control groups were also evaluated. RESULTS: MRI
      acquisition protocols had little effect on the PET count rate, and the PET
      instrumentation had little effect on image contrast during acidoCEST MRI,
      verifying that [18F]FDG PET and acidoCEST MRI can be performed simultaneously.
      The average SUVmax of the tumor model had a significant decrease after 7 days of
      treatment with metformin, as expected. The average tumor pHe decreased after 7
      days of metformin treatment, which reflected the inhibition of the consumption of
      cytosolic lactic acid caused by metformin. However, the average SUVmax of the
      tumor model was not significantly different between the metformin-treated and
      control groups after 7 days of treatment, and average pHe was also not
      significantly different between these groups. For comparison, the combination of
      average SUVmax and pHe measurements significantly differed between the treatment
      group and control group on Day 7. CONCLUSIONS: [18F]FDG PET and acidoCEST MRI
      studies can be performed simultaneously. The synergistic combination of assessing
      glucose uptake and tumor acidosis can improve differentiation of a drug-treated
      group from a control group during drug treatment of a tumor model.

PMID- 29374342
TI  - Multimodal MR imaging in hepatic encephalopathy: state of the art.
AB  - Hepatic encephalopathy (HE) is a neurological or neuropsychological complication
      due to liver failure or portosystemic shunting. The clinical manifestation is
      highly variable, which can exhibit mild cognitive or motor impairment initially,
      or gradually progress to a coma, even death, without treatment. Neuroimaging
      plays a critical role in uncovering the neural mechanism of HE. In particular,
      multimodality MR imaging is able to assess both structural and functional
      derangements of the brain with HE in focal or neural network perspectives. In
      recent years, there has been rapid development in novel MR technologies and
      applications to investigate the pathophysiological mechanism of HE. Therefore, it
      is necessary to update the latest MR findings regarding HE by use of
      multimodality MRI to refine and deepen our understanding of the neural traits in
      HE. Herein, this review highlights the latest MR imaging findings in HE to
      refresh our understanding of MRI application in HE.

PMID- 29374344
TI  - Assessment of antimicrobial drug administration and antimicrobial residues in
      food animals in Enugu State, Nigeria.
AB  - Imprudent administration of antimicrobial drugs in food-producing animals can
      facilitate the development and spread of antimicrobial-resistant organisms and
      also enhance the occurrence of antimicrobial residue in animal products. This
      study was undertaken to assess antimicrobial drug administration to food animals
      in livestock farms in Enugu State and determine livestock farmers' awareness on
      the consequences of imprudent antimicrobial administration to food animals and
      finally the prevalence of antimicrobial drug residues in edible tissues of cattle
      and pigs in the state. Structured questionnaire was used to extract information
      on antimicrobial drug administration and consequences of irresponsible use of
      antimicrobials in food animals from 109 livestock farms/farmers randomly selected
      using multi-stage sampling technique. Premi(r) test technology (R-Biopharm,
      Germany) was used to screen for antimicrobial residues in edible tissues from 300
      carcasses consisting of 165 cattle and 135 pigs slaughtered for human consumption
      in two major slaughterhouses in Enugu State. Tetracyclines (90.8%), penicillins
      and beta-lactams (89.9%), and aminoglycoside (57.8%) were the classes of
      antimicrobials most frequently administered to food animals in the farms
      surveyed. Withdrawal period was not observed in 65% of the farms. About 30% of
      cattle and 23% of pig carcasses screened contained detectable amounts of
      antimicrobial residues. There is widespread indiscriminate administration of
      antimicrobial drugs in food animals in Enugu State. This underscores the need for
      public enlightenment on prudent use of antimicrobial drugs in food-producing
      animals in order to preserve the therapeutic efficacy for sustainable livestock
      production and to safeguard human health.

PMID- 29374345
TI  - Influence of green grass-based diets on growth and reproductive performance in
      dairy heifers.
AB  - The objective of this study was to monitor the changes in growth, dry matter
      intake, and blood profiles (nutrition and reproductive hormones) of dairy heifers
      in response to green grass-based diets. Twelve crossbred heifers were equally
      divided into group 1: rice straw and concentrate; group 2: rice straw, green
      grass, and concentrate; group 3: green grass and concentrate; group 4: green
      grass, soybean hay, and concentrate. Dry matter intake in group 4 was found 6%
      higher (P < 0.05) than group 1. Negative body weight gain was found in group 1
      and group 2 showed 14% higher body weight gain per 30 days compared to groups 3
      and 4 (P < 0.05). Heifers in group 4 had significantly (P < 0.05) higher heart
      girth gain, serum albumin, urea, and blood urea nitrogen than the heifers in
      other groups. Endocrine parameters were found similar among groups. Overall,
      supply of green grass especially a mix of leguminous and non-leguminous was found
      advantageous in heifer feeding.

PMID- 29374347
TI  - Association between preoperative thyrotrophin and clinicopathological and
      aggressive features of papillary thyroid cancer.
AB  - PURPOSE: We aimed to investigate the relation between preoperative serum
      thyrotrophin (TSH) and clinicopathological features in patients with papillary
      thyroid carcinoma (PTC) and microcarcinoma (PTMC). METHODS: Patients who
      underwent thyroidectomy and diagnosed to have benign nodular disease or PTC/PTMC
      in our clinic were evaluated retrospectively. Patients with a previous history of
      thyroid surgery, patients using antithyroid medications or thyroid hormone and
      patients with tumors known to be unresponsive to TSH were excluded. RESULTS: Data
      of 1632 patients were analyzed. Histopathological diagnosis was benign in 969
      (59.4%) and malignant in 663 (40.6%) patients. Preoperative median serum TSH was
      significantly higher in malignant compared to benign group (1.41 IU/dL vs. 0.98
      IU/dL, p < 0.001). Malignancy risk increased gradually as going from
      hyperthyroidism to euthyroidism and hypothyroidism (20, 40.6, and 59.1%,
      respectively, p < 0.05). Serum TSH was lowest in benign nodular disease, higher
      in PTMC and highest in PTC (p < 0.001). This was also true when patients with
      positive antithyroid peroxidase/antithyroglobulin and with lymphocytic
      thyroiditis were excluded from the analysis (p < 0.001). Serum TSH was higher in
      patients with bilateral tumor, capsular invasion and lymph node metastasis (LNM)
      compared to patients with unilateral tumor, without capsule invasion and without
      LNM, respectively (p = 0.036, p = 0.002, and p = 0.001, respectively). Patients
      with aggressive variant PTC had higher serum TSH than nonaggressive ones (p <
      0.05). CONCLUSION: Preoperative serum TSH is associated with PTMC, PTC and LNM.
      Serum TSH seems to be related with thyroid cancer regardless of autoimmunity.
      With the present study, for the first time, we showed an association between
      serum TSH and aggressive variants of PTC.

PMID- 29374348
TI  - Driver electronics design and control for a total artificial heart linear motor.
AB  - For any implantable device size and efficiency are critical properties. Thus, a
      linear motor for a Total Artificial Heart was optimized with focus on driver
      electronics and control strategies. Hardware requirements were defined from power
      supply and motor setup. Four full bridges were chosen for the power electronics.
      Shunt resistors were set up for current measurement. Unipolar and bipolar
      switching for power electronics control were compared regarding current ripple
      and power losses. Here, unipolar switching showed smaller current ripple and
      required less power to create the necessary motor forces. Based on calculations
      for minimal power losses Lorentz force was distributed to the actor's four coils.
      The distribution was determined as ratio of effective magnetic flux through each
      coil, which was captured by a force test rig. Static and dynamic measurements
      under physiological conditions analyzed interaction of control and hardware and
      all efficiencies were over 89%. In conclusion, the designed electronics,
      optimized control strategy and applied current distribution create the required
      motor force and perform optimal under physiological conditions. The developed
      driver electronics and control offer optimized size and efficiency for any
      implantable or portable device with multiple independent motor coils. Graphical
      Abstract ?.

PMID- 29374346
TI  - Accessing Gene Expression in Treatment-Resistant Schizophrenia.
AB  - Schizophrenia (SCZ) is a mental disorder arising from a complex interaction of
      genetic and environmental factors. It has been suggested that treatment-resistant
      schizophrenia (TRS) is a distinct, more severe, and homogenous subgroup of
      schizophrenia that could present specific biological markers. Our aim was to
      characterize expression of target genes in blood of TRS patients compared with
      non-TRS (NTRS) patients and healthy controls (HC). TRS has been defined using
      failure to respond to two previous antipsychotic trials. We hypothesized that
      genes involved in neurodevelopment, myelination, neuroplasticity,
      neurotransmission, and miRNA processing could be involved in treatment
      resistance; then, we investigated 13 genes related to those processes in 256
      subjects, being 94 healthy controls and 162 schizophrenia patients treated with
      antipsychotics. Of those, 78 were TRS patients and 84 were NTRS patients.
      Peripheral blood samples were collected from all subjects and RNA was isolated.
      Gene expression analysis was performed using the TaqMan low-density array (TLDA)
      technology. To verify the influence of expression quantitative trait loci
      (eQTLs), we evaluated single-nucleotide polymorphism (SNP) of all genes using
      data from GTEx Project. SNP genotypes were obtained from HumanOmniExpress
      BeadChip. We did not detect gene expression differences between TRS and NTRS
      subjects, indicating candidate genes specific to treatment resistance. We
      detected an upregulation of CNR1 and UFD1L gene expression in patients (TRS and
      NTRS groups) when compared to controls, that may be associated with the release
      of neurotransmitters, which can influence neuronal plasticity, or with a stress
      response-activating protein degradation. DICER1 and AKT1 expression increased
      slightly across the groups and could differentiate only the extreme opposite
      groups, HC and TRS. Both genes act in heterogeneous pathways, such as cell
      signaling and miRNA processing, and seem to have an increased demand in the TRS
      group. We did not detect any eQTLs in our sample that could explain differences
      in mRNA levels, suggesting a possible regulation by other mechanism, not driven
      by genotypes. Our data strengthen the importance of several biological pathways
      involved in the schizophrenia refractoriness and severity, adding knowledge to
      develop more effective treatments in the future.

PMID- 29374349
TI  - Pyogenic Granuloma of the Jejunum: an Unusual Cause of Anemia.
AB  - Pyogenic granuloma is a benign vascular lesion, uncommon in the gastrointestinal
      tract, and extremely rare in the small bowel. The diagnosis can be challenging
      prior to surgery, because of its unusual endoscopic appearance.We present a case
      of pyogenic granuloma of the jejunum diagnosed by capsule endoscopy and double
      balloon enteroscopy and successfully managed by surgical resection.

PMID- 29374350
TI  - Intraoperative Nefopam Reduces Acute Postoperative Pain after Laparoscopic
      Gastrectomy: a Prospective, Randomized Study.
AB  - BACKGROUND: We assessed whether intraoperative nefopam would reduce opioid
      consumption and relieve postoperative pain in patients undergoing laparoscopic
      gastrectomy. METHODS: The 60 enrolled patients were randomly assigned to the
      control (n = 32) or nefopam (n = 28) group. All patients were blinded to their
      group assignment. We administered 100 ml of normal saline only (control group) or
      20 mg of nefopam mixed in 100 ml normal saline (nefopam group) after anesthesia
      induction and at the end of surgery. The cumulative amount of fentanyl via
      intravenous patient-controlled analgesia (PCA), incidence of rescue analgesic
      medication, and numerical rating scale (NRS) for postoperative pain were
      evaluated along with the total remifentanil consumption. RESULTS: The mean
      infusion rate of remifentanil was significantly lower in the nefopam group (0.08
      +/- 0.05 MUg/kg/min) than in the control group (0.13 +/- 0.06 MUg/kg/min) (P <
      0.001). Patients in the nefopam group required less fentanyl via intravenous PCA
      than those in the control group during the first 6 h after surgery (323.8 +/-
      119.3 MUg vs. 421.2 +/- 151.6 MUg, P = 0.009). Additionally, fewer patients in
      the nefopam group than in the control group received a rescue analgesic during
      the initial 6 h postoperatively (78.6 vs. 96.9%, P = 0.028). The NRS measured
      while patients were in the post-anesthetic care unit was significantly lower in
      the nefopam group than in the control group (3.8 +/- 1.1 vs. 4.8 +/- 1.4, P =
      0.012). The subsequent NRS obtained after patients had been transferred to the
      general ward was comparable between the two groups during the following
      postoperative period. CONCLUSIONS: Intraoperative nefopam decreased postoperative
      pain and opioid consumption in the acute postoperative period after laparoscopic
      gastrectomy. Hence, nefopam may be considered as a component of multimodal
      analgesia after laparoscopic gastrectomy.

PMID- 29374351
TI  - miR-328 mediates a metabolic shift in colon cancer cells by targeting
      SLC2A1/GLUT1.
AB  - PURPOSE: Increasing evidence shows that altered metabolism is a critical hallmark
      in colon cancer. There is a strong need to explore the molecular mechanisms
      underlying cancer metabolism. Whether the aberrant expression of microRNAs
      contributes to cancer metabolism is not fully understood. miR-328 is a putative
      potential target of SLC2A1, but the regulating mechanism between them remains
      unknown. We have examined whether miR-328 directly regulates SLC2A1/GLUT1
      expression in colon cancer cells. METHODS: We performed in silico bioinformatic
      analyses to identify miR-328-mediated molecular pathways and targets. We also
      performed luciferase assays and western blot analyses in LOVO and SW480 colon
      cancer cell lines. In addition, we assessed miR-328 expression in 47 paired tumor
      and normal tissue specimens from resected colon cancer patients. RESULTS:
      Luciferase reporter assays showed that miR-328 directly targeted SLC2A1 3'
      untranslated region (UTR), with a significant decrease in luciferase activity in
      both LOVO and SW480 cell lines. These results were validated by western blot. miR
      328 expression was significantly downregulated in tumor tissue compared with
      paired normal tissue. CONCLUSIONS: Our results show that miR-328 targets
      SLC2A1/GLUT1. We suggest that miR-328 may be involved in the orchestration of the
      Warburg effect in colon cancer cells. Furthermore, miR-328 expression is reduced
      in colon cancer patients and thus inversely correlates with the classically
      reported upregulated SLC2A1/GLUT1 expression in tumors.

PMID- 29374352
TI  - Image Guidance Technologies for Interventional Pain Procedures: Ultrasound,
      Fluoroscopy, and CT.
AB  - Chronic pain is a common medical condition. Patients who suffer uncontrolled
      chronic pain may require interventions including spinal injections and various
      nerve blocks. Interventional procedures have evolved and improved over time since
      epidural injection was first introduced for low back pain and sciatica in 1901.
      One of the major contributors in the improvement of these interventions is the
      advancement of imaging guidance technologies. The utilization of image guidance
      has dramatically improved the accuracy and safety of these interventions. The
      first image guidance technology adopted by pain specialists was fluoroscopy. This
      was followed by CT and ultrasound. Fluoroscopy can be used to visualize bony
      structures of the spine. It is still the most commonly used guidance technology
      in spinal injections. In the recent years, ultrasound guidance has been
      increasingly adopted by interventionists to perform various injections. Because
      its ability to visualize soft tissue, vessels, and nerves, this guidance
      technology appears to be a better option than fluoroscopy for interventions
      including SGB and celiac plexus blocks, when visualization of the vessels may
      prevent intravascular injection. The current evidence indicates the efficacies of
      these interventions are similar between ultrasound guidance and fluoroscopy
      guidance for SGB and celiac plexus blocks. For facet injections and interlaminar
      epidural steroid injections, it is important to visualize bony structures in
      order to perform these procedures accurately and safely. It is worth noting that
      facet joint injections can be done under ultrasound guidance with equivalent
      efficacy to fluoroscopic guidance. However, obese patients may present challenge
      for ultrasound guidance due to its poor visualization of deep anatomical
      structures. Regarding transforaminal epidural steroid injections, there are
      limited evidence to support that ultrasound guidance technology has equivalent
      efficacy and less complications comparing to fluoroscopy. However, further
      studies are required to prove the efficacy of ultrasound-guided transforaminal
      epidural injections. SI joint is unique due to its multiplanar orientation,
      irregular joint gap, partial ankylosis, and thick dorsal and interosseous
      ligament. Therefore, it can be difficult to access the joint space with
      fluoroscopic guidance and ultrasound guidance. CT scan, with its cross-sectional
      images, can identify posterior joint gap, is most likely the best guidance
      technology for this intervention. Intercostal nerves lie in the subcostal grove
      close to the plural space. Significant risk of pneumothorax is associated with
      intercostal blocks. Ultrasound can provide visualization of ribs and pleura.
      Therefore, it may improve the accuracy of the injection and reduce the risk of
      pneumothorax. At present time, most pain specialists are familiar with
      fluoroscopic guidance techniques, and fluoroscopic machines are readily available
      in the pain clinics. In the contrast, CT guidance can only be performed in
      specially equipped facilities. Ultrasound machine is generally portable and
      inexpensive in comparison to CT scanner and fluoroscopic machine. As pain
      specialists continue to improve their patient care, ultrasound and CT guidance
      will undoubtedly be incorporated more into the pain management practice. This
      review is based on a paucity of clinical evidence to compare these guidance
      technologies; clearly, more clinical studies is needed to further elucidate the
      pro and cons of each guidance method for various pain management interventions.

PMID- 29374353
TI  - Gouty arthritis: decision-making following dual-energy CT scan in clinical
      practice, a retrospective analysis.
AB  - To establish whether dual-energy CT (DECT) is a diagnostic tool, i.e., associated
      with initiation or discontinuation of a urate lowering drug (ULD). Secondly, to
      determine whether DECT results (gout deposition y/n) can be predicted by clinical
      and laboratory variables. Digital medical records of 147 consecutive patients
      with clinical suspicion of gout were analyzed retrospectively. Clinical data
      including medication before and after DECT, lab results, and results from
      diagnostic joint aspiration and DECT were collected. The relationship between
      DECT results and clinical and laboratory results was evaluated by univariate
      regression analyses; predictors showing a p < 0.10 were entered in a multivariate
      logistic regression model with the DECT result as outcome variable. A backward
      stepwise technique was applied. After the DECT, 104 of these patients had a
      clinical diagnosis of gout based on the clinical judgment of the rheumatologist,
      and in 84 of these patients, the diagnosis was confirmed by demonstration of
      monosodium urate (MSU) crystals in synovial fluid (SF) or by positive DECT. After
      DECT, the current ULD was modified in 33 (22.4%) of patients; in 29 of them, ULD
      was started and in 1 it was intensified. Following DECT, the current ULD was
      stopped in three patients. In the multivariable regression model, cardiovascular
      disease (OR 3.07, 95% CI 1.26-7.47), disease duration (OR 1.008, 95% CI 1.001
      1.016), frequency of attack (OR 1.23, 95% CI 1.07-1.42), and creatinine clearance
      (OR 2.03, 95% CI 0.91-1.00) were independently associated with positive DECT
      results. We found that the DECT result increases the confidence of the
      prescribers in their decision to initiation or discontinuation of urate lowering
      therapy regimen in of mono- or oligoarthritis. It may be a useful imaging tool
      for patients who cannot undergo joint aspiration because of contraindications or
      with difficult to aspirate joints, or those who refuse joint aspiration. We also
      suggest the use of DECT in cases where a definitive diagnosis cannot be made from
      signs, symptoms, and MSU analysis alone.

PMID- 29374354
TI  - Missing motoric manipulations: rethinking the imaging of the ventral striatum and
      dopamine in human reward.
AB  - Human neuroimaging studies of natural rewards and drugs of abuse frequently assay
      the brain's response to stimuli that, through Pavlovian learning, have come to be
      associated with a drug's rewarding properties. This might be characterized as a
      'sensorial' view of the brain's reward system, insofar as the paradigms are
      designed to elicit responses to a reward's (drug's) sight, aroma, or flavor. A
      different field of research nevertheless suggests that the mesolimbic dopamine
      system may also be critically involved in the motor behaviors provoked by such
      stimuli. This brief review and commentary surveys some of the preclinical data
      supporting this more "efferent" (motoric) view of the brain's reward system, and
      discusses what such findings might mean for how human brain imaging studies of
      natural rewards and drugs of abuse are designed.

PMID- 29374355
TI  - Physical activity mitigates adverse effect of metabolic syndrome on vessels and
      brain.
AB  - Metabolic syndrome (MetS) adversely affects the vasculature and cerebral white
      matter (CWM) integrity. Arterial stiffening has been associated with diminished
      CWM integrity. Physical activity (PA) can ameliorate components of MetS and
      subsequently affect arterial stiffening and CWM integrity. Our aim was to
      determine the role of PA on mitigating the adverse influence of MetS on arterial
      stiffness and CWM integrity. In a cross-sectional study design, sixty-six middle
      aged adults (40-62 years) composed of 18 sedentary MetS (Sed MetS), 21 physically
      active MetS (Active MetS), and 27 healthy individuals absent of MetS risk factors
      were studied. Carotid artery stiffness was assessed via simultaneous ultrasound
      and tonometry. CWM integrity was measured using diffusion tensor imaging (DTI)
      through metrics of fractional anisotropy (FA) and mean diffusivity (MD). Carotid
      beta-stiffness index in Active MetS was lower than Sed MetS but was not different
      from Healthy controls (6.6 +/- 1.5, 7.7 +/- 2.1, and 5.6 +/- 1.6 au, p = 0.001).
      CWM integrity was significantly greater in Active MetS subjects compared to Sed
      MetS subjects but statistically equal to Healthy controls in the anterior limb of
      the internal capsule, and splenium of the corpus callosum, uncinate fasciculus,
      and superior corona radiata (all p < 0.05). Middle-aged individuals with MetS who
      habitually perform PA demonstrated lower arterial stiffness and more favorable
      CWM integrity than their sedentary peers, indicating that PA may be effective in
      mitigating the adverse effects of MetS on the vasculature and brain at midlife.

PMID- 29374356
TI  - Altered intrinsic brain activity and memory performance improvement in patients
      with end-stage renal disease during a single dialysis session.
AB  - Memory deficits are considered to have a great influence on self-management,
      dietary restriction and therapeutic regimen for end-stage renal disease (ESRD)
      patients with dialysis treatment. This study was aim to investigate the
      spontaneous brain activity and its relationship with memory performance in ESRD
      patients before dialysis (T1) and after 24 h (T2) during a single dialysis
      session. 23 ESRD patients and 25 matched healthy controls (HCs) were scanned
      using functional magnetic resonance imaging (fMRI) at T1, and all patients were
      also scanned at T2. Amplitude of low-frequency fluctuation (ALFF) and regional
      homogeneity (ReHo) methods were used to evaluate the spontaneous brain activity
      between two groups. The Auditory Verbal Learning Test-Huashan version (AVLT-H)
      was performed to assess memory function. Compared with HCs, ESRD group showed a
      significant decreases in the immediate recall total score (IR-S), short-term
      delayed recall score (SR-S), and long-term delayed recall score (LR-S) at T1. IR
      S, SR-S, LR-S and recognition score (REC-S) were significantly increased at T2.
      Compared with HCs at T1, ESRD patients showed that the lower mean ALFF (mALFF)
      values were mainly located in dorsolateral prefrontal cortex (DLPFC), medial
      frontal gyrus, and precuneus. Higher ReHo in the bilateral inferior temporal
      gyrus and left hippocampus and lower ReHo in the right precentral gyrus, anterior
      cingulate cortex were found at T1 too. The mALFF values of the DLPFC and
      precuneus were significantly increased during a dialysis session, while no
      significantly difference of ReHo region was found. Furthermore, the increased
      mALFF values of the DLPFC were significantly positively correlated with the
      improvement in the IR-S. Our results indicated that increased regional
      spontaneous activity of the DLPFC may reflect memory performance improvement
      after a single dialysis treatment, which may provide insight into the effect of
      hemodialysis on spontaneous brain function during a single dialysis session.

PMID- 29374357
TI  - Do Words Matter? Stigmatizing Language and the Transmission of Bias in the
      Medical Record.
AB  - BACKGROUND: Clinician bias contributes to healthcare disparities, and the
      language used to describe a patient may reflect that bias. Although medical
      records are an integral method of communicating about patients, no studies have
      evaluated patient records as a means of transmitting bias from one clinician to
      another. OBJECTIVE: To assess whether stigmatizing language written in a patient
      medical record is associated with a subsequent physician-in-training's attitudes
      towards the patient and clinical decision-making. DESIGN: Randomized vignette
      study of two chart notes employing stigmatizing versus neutral language to
      describe the same hypothetical patient, a 28-year-old man with sickle cell
      disease. PARTICIPANTS: A total of 413 physicians-in-training: medical students
      and residents in internal and emergency medicine programs at an urban academic
      medical center (54% response rate). MAIN MEASURES: Attitudes towards the
      hypothetical patient using the previously validated Positive Attitudes towards
      Sickle Cell Patients Scale (range 7-35) and pain management decisions (residents
      only) using two multiple-choice questions (composite range 2-7 representing
      intensity of pain treatment). KEY RESULTS: Exposure to the stigmatizing language
      note was associated with more negative attitudes towards the patient (20.6
      stigmatizing vs. 25.6 neutral, p < 0.001). Furthermore, reading the stigmatizing
      language note was associated with less aggressive management of the patient's
      pain (5.56 stigmatizing vs. 6.22 neutral, p = 0.003). CONCLUSIONS: Stigmatizing
      language used in medical records to describe patients can influence subsequent
      physicians-in-training in terms of their attitudes towards the patient and their
      medication prescribing behavior. This is an important and overlooked pathway by
      which bias can be propagated from one clinician to another. Attention to the
      language used in medical records may help to promote patient-centered care and to
      reduce healthcare disparities for stigmatized populations.

PMID- 29374359
TI  - Long-Term Cognitive Impairment after Hospitalization for Community-Acquired
      Pneumonia: a Prospective Cohort Study.
AB  - BACKGROUND: Recent studies suggest older patients hospitalized for community
      acquired pneumonia are at risk for new-onset cognitive impairment. The
      characteristics of long-term cognitive impairment after pneumonia, however, have
      not been elucidated. OBJECTIVE: To characterize long-term cognitive impairment
      among adults of all ages hospitalized for community-acquired pneumonia. DESIGN:
      Prospective cohort study. PARTICIPANTS: Adults without severe preexisting
      cognitive impairment who were hospitalized with community-acquired pneumonia.
      MAIN MEASURES: At enrollment, we estimated baseline cognitive function with the
      Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2-
      and 12-month follow-up, we assessed cognition using the Repeatable Battery for
      the Assessment of Neuropsychological Status (RBANS) and tests of executive
      function, diagnosing cognitive impairment when results were >= 1.5 standard
      deviations below published age-adjusted means for the general population. We also
      identified subtypes of mild cognitive impairment using standard definitions. KEY
      RESULTS: We assessed 58 (73%) of 80 patients who survived to 2-month follow-up
      and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of
      survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild
      cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2
      months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS.
      Moderate-to-severe cognitive impairment was common among adults >= 65 years [4/13
      (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of
      those < 65 years [10/43 (23%) and 8/43 (19%) at 2 and 12 months, respectively].
      Deficits were most often noted in visuospatial function, attention, and memory.
      CONCLUSIONS: A year after hospitalization for community-acquired pneumonia,
      moderate-to-severe impairment in multiple cognitive domains affected one-third of
      patients >= 65 years old and 20% of younger patients, and another third of
      survivors had mild cognitive impairment.

PMID- 29374358
TI  - Identifying Older Adults at Risk of Delirium Following Elective Surgery: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Postoperative delirium is a common preventable complication
      experienced by older adults undergoing elective surgery. In this systematic
      review and meta-analysis, we identified prognostic factors associated with the
      risk of postoperative delirium among older adults undergoing elective surgery.
      METHODS: Medline, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials,
      and AgeLine were searched for articles published between inception and April 21,
      2016. A total of 5692 titles and abstracts were screened in duplicate for
      possible inclusion. Studies using any method for diagnosing delirium were
      eligible. Two reviewers independently completed all data extraction and quality
      assessments using the Cochrane Risk-of-Bias Tool for randomized controlled trials
      (RCTs) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random effects
      meta-analysis models were used to derive pooled effect estimates. RESULTS: Forty
      one studies (9384 patients) reported delirium-related prognostic factors. Among
      our included studies, the pooled incidence of postoperative delirium was 18.4%
      (95% confidence interval [CI] 14.3-23.3%, number needed to follow [NNF] = 6).
      Geriatric syndromes were important predictors of delirium, namely history of
      delirium (odds ratio [OR] 6.4, 95% CI 2.2-17.9), frailty (OR 4.1, 95% CI 1.4
      11.7), cognitive impairment (OR 2.7, 95% CI 1.9-3.8), impairment in activities of
      daily living (ADLs; OR 2.1, 95% CI 1.6-2.6), and impairment in instrumental
      activities of daily living (IADLs; OR 1.9, 95% CI 1.3-2.8). Potentially
      modifiable prognostic factors such as psychotropic medication use (OR 2.3, 95% CI
      1.4-3.6) and smoking status (OR 1.8 95% CI 1.3-2.4) were also identified.
      Caregiver support was associated with lower odds of postoperative delirium (OR
      0.69, 95% CI 0.52-0.91). DISCUSSION: Though caution must be used in interpreting
      meta-analyses of non-randomized studies due to the potential influence of
      unmeasured confounding, we identified potentially modifiable prognostic factors
      including frailty and psychotropic medication use that should be targeted to
      optimize care.

PMID- 29374360
TI  - How Primary Care Providers Talk to Patients about Genome Sequencing Results:
      Risk, Rationale, and Recommendation.
AB  - BACKGROUND: Genomics will play an increasingly prominent role in clinical
      medicine. OBJECTIVE: To describe how primary care physicians (PCPs) discuss and
      make clinical recommendations about genome sequencing results. DESIGN:
      Qualitative analysis. PARTICIPANTS: PCPs and their generally healthy patients
      undergoing genome sequencing. APPROACH: Patients received clinical genome reports
      that included four categories of results: monogenic disease risk variants (if
      present), carrier status, five pharmacogenetics results, and polygenic risk
      estimates for eight cardiometabolic traits. Patients' office visits with their
      PCPs were audio-recorded, and summative content analysis was used to describe how
      PCPs discussed genomic results. KEY RESULTS: For each genomic result discussed in
      48 PCP-patient visits, we identified a "take-home" message (recommendation),
      categorized as continuing current management, further treatment, further
      evaluation, behavior change, remembering for future care, or sharing with family
      members. We analyzed how PCPs came to each recommendation by identifying 1) how
      they described the risk or importance of the given result and 2) the rationale
      they gave for translating that risk into a specific recommendation. Quantitative
      analysis showed that continuing current management was the most commonly coded
      recommendation across results overall (492/749, 66%) and for each individual
      result type except monogenic disease risk results. Pharmacogenetics was the most
      common result type to prompt a recommendation to remember for future care
      (94/119, 79%); carrier status was the most common type prompting a recommendation
      to share with family members (45/54, 83%); and polygenic results were the most
      common type prompting a behavior change recommendation (55/58, 95%). One-fifth of
      recommendation codes associated with monogenic results were for further
      evaluation (6/24, 25%). Rationales for these recommendations included patient
      context, family context, and scientific/clinical limitations of sequencing.
      CONCLUSIONS: PCPs distinguish substantive differences among categories of genome
      sequencing results and use clinical judgment to justify continuing current
      management in generally healthy patients with genomic results.

PMID- 29374363
TI  - Non-coding RNAs, epigenetics, and cancer: tying it all together.
AB  - While only a small part of the human genome encodes for proteins, biological
      functions for the so-called junk genome are increasingly being recognized through
      high-throughput technologies and mechanistic experimental studies. Indeed, novel
      mechanisms of gene regulation are being discovered that require coordinated
      interaction between DNA, RNA, and proteins. Therefore, interdisciplinary efforts
      are still needed to decipher these complex transcriptional networks. In this
      review, we discuss how non-coding RNAs (ncRNAs) are epigenetically regulated in
      cancer and metastases and consequently how ncRNAs participate in the sculpting of
      the epigenetic profile of a cancer cell, thus modulating the expression of other
      RNA molecules. In the latter case, ncRNAs not only affect the DNA methylation
      status of certain genomic loci but also interact with histone-modifying
      complexes, changing the structure of the chromatin itself. We present several
      examples of epigenetic changes causing aberrant expression of ncRNAs in the
      context of tumor progression. Interestingly, there are also important epigenetic
      changes and transcriptional regulatory effects derived from their aberrant
      expression. As ncRNAs can also be used as biomarkers for diagnosis and prognosis
      or explored as potential targets, we present insights into the use of ncRNAs for
      targeted cancer therapy.

PMID- 29374361
TI  - Targeting Senescent Cells in Fibrosis: Pathology, Paradox, and Practical
      Considerations.
AB  - PURPOSE OF THE REVIEW: Senescent cells have the capacity to both effect and limit
      fibrosis. Senotherapeutics target senescent cells to improve aging conditions.
      Here, we review the contexts in which senescent cells mediate wound healing and
      fibrotic pathology and the potential utility of senotherapeutic drugs for
      treatment of fibrotic disease. RECENT FINDINGS: Multi-action and temporal
      considerations influence deleterious versus beneficial actions of senescent
      cells. Acutely generated senescent cells can limit proliferation, and the
      senescence-associated secretory phenotype (SASP) contains factors that can
      facilitate tissue repair. Long-lived senescent cells that evade clearance or are
      generated outside of programmed remodeling can deplete the progenitor pool to
      exhaust regenerative capacity and through the SASP, stimulate continual
      activation, leading to disorganized tissue architecture, fibrotic damage, sterile
      inflammation, and induction of bystander senescence. Senescent cells contribute
      to fibrotic pathogenesis in multiple tissues, including the liver, kidney, and
      lung. Senotherapeutics may be a viable strategy for treatment of a range of
      fibrotic conditions.

PMID- 29374362
TI  - The regulatory network analysis of long noncoding RNAs in human colorectal
      cancer.
AB  - Colorectal cancer (CRC) is among one of the most prevalent and lethiferous
      diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to
      function as a key regulatory factor in human cancer, but the potential regulatory
      mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated
      several expression profiles to obtain 55 differentially expressed (DE) lncRNAs.
      We first detected lncRNA interactions with transcription factors, microRNAs,
      mRNAs, and RNA-binding proteins to construct a regulatory network and then create
      functional enrichment analyses for them using bioinformatics approaches. We found
      the upregulated genes in the regulatory network are enriched in cell cycle and
      DNA damage response, while the downregulated genes are enriched in cell
      differentiation, cellular response, and cell signaling. We then employed module
      based methods to mine several intriguing modules from the overall network, which
      helps to classify the functions of genes more specifically. Next, we confirmed
      the validity of our network by comparisons with a randomized network using
      computational method. Finally, we attempted to annotate lncRNA functions based on
      the regulatory network, which indicated its potential application. Our study of
      the lncRNA regulatory network provided significant clues to unveil lncRNAs
      potential regulatory mechanisms in CRC and laid a foundation for further
      experimental investigation.

PMID- 29374364
TI  - Effectiveness of laser adjunctive therapy for surgical treatment of gingival
      recession with flap graft techniques: a systematic review and meta-analysis.
AB  - Various flap graft techniques in the treatment of gingival recession have already
      been reported in the literatures for root coverage. Laser therapy has effects of
      ablative, hemostatic, and decontamination. Therefore, we performed a meta
      analysis of randomized controlled trials (RCTs) to compare the efficacy of flap
      surgery combined with laser with surgery alone for treating gingival recession.
      The studies were searched from PubMed, Embase, Web of science, and the Cochrane
      Central Register of Controlled Trials by two reviewers up to August 2017. The
      quality of RCTs was assessed by Cochrane Handbook. Data were extracted from
      studies and analyzed by Review Manager 5.3. 95% confidence interval (CI) and risk
      ratio (RR) were calculated for dichotomous data. Seven RCTs with 173 patients and
      296 teeth were included in the meta-analysis. We found no statistically
      significant differences between two groups in GRD (gingival recession depth) (P =
      0.21), GRW (gingival recession width) (P = 0.92), RES (root esthetic score) (P =
      0.21), and CRC (complete root coverage) (P = 0.09). Statistically significant
      differences were found between two groups in the WKT (width of keratinized
      tissue) (P < 0.0001) and 1-year follow-up of PD (probing depth) (P = 0.03) and
      CAL (clinical attachment level) (P < 0.00001). The meta-analysis found that
      surgery with laser therapy provided clinical advantages in terms of WKT and 1
      year follow-up of PD and CAL. However, flap graft associated with laser did not
      offer additional benefit to root coverage and esthetics in treating gingival
      recession. More long-term studies are required to assess these parameters.

PMID- 29374366
TI  - Conspecific and Heterogeneric Lacewings Respond to (Z)-4-Tridecene Identified
      from Chrysopa formosa (Neuroptera: Chrysopidae).
AB  - Green lacewings (Chrysopidae) are predators of soft-bodied pest insects and are
      among the most important biological control agents in crop protection. Chrysopa
      spp. are of special importance since, unlike most green lacewing species, adults
      are also predatory. The current study was undertaken in search of Chrysopa
      formosa compounds with semiochemical activity. Using coupled gas chromatography
      electroantennography (GC-EAG), head and thorax extracts of C. formosa elicited
      EAG responses to a compound subsequently identified by coupled GC/mass
      spectrometry, microchemistry, chemical synthesis and GC peak enhancement as (Z)-4
      tridecene. In field experiments, this compound decreased attraction of adult C.
      formosa to (1R,4aS,7S,7aR)-nepetalactol and that of Chrysoperla carnea species
      complex to a ternary floral lure, with the inhibitory effect found to be dose
      dependent. Our results suggest that (Z)-4-tridecene may serve as a general
      warning signal among multiple green lacewing species. Perspectives for potential
      practical applications are discussed.

PMID- 29374365
TI  - Liposomal Form of Tetra(Aryl)Tetracyanoporphyrazine: Physical Properties and
      Photodynamic Activity In Vitro.
AB  - Tetra(aryl)tetracyanoporphyrazines are the promising group of dyes for
      photodynamic therapy of tumors with unique combination of photosensitizer
      properties and sensitivity of fluorescence parameters to the environment
      viscosity. However, in vivo application of such hydrophobic photosensitizers
      requires using of drug carriers ensuring efficient delivery to the tumor site.
      The present study is focused on obtaining liposomes loaded with tetrakis(4
      benzyloxyphenyl)tetracyanoporphyrazine and examining their properties depending
      on lipid composition. An efficient loading of the dye and a high long-term
      stability were proved for the liposomes composed of phosphatidylcholine with
      cholesterol and phosphatidylglycerol. This can be explained by the presence of
      negatively charged lipids in the bilayer and, as a consequence, a high value of
      the surface potential. A high rate of cellular uptake and a strong photoinduced
      toxicity give the prerequisites for the further use of the liposomal form of the
      photosensitizer for photodynamic therapy of tumors.

PMID- 29374367
TI  - The Genetics of Food Allergy.
AB  - PURPOSE OF REVIEW: Food allergy likely arises from a complex interplay between
      environmental triggers and genetic susceptibility. Here, we review recent studies
      that have investigated the genetic pathways and mechanisms that may contribute to
      the pathogenesis of food allergy. RECENT FINDINGS: A heritability component of
      food allergy has been observed in multiple studies. A number of monogenic
      diseases characterized by food allergy have elucidated pathways that may be
      important in pathogenesis. Several population-based genetic variants associated
      with food allergy have also been identified. The genetic mechanisms that play a
      role in the development of food allergy are heterogeneous and complex. Advances
      in our understanding of the genetics of food allergy, and how this predisposition
      interacts with environmental exposures to lead to disease, will improve our
      understanding of the key pathways leading to food allergy and inform more
      effective prevention and treatment strategies.

PMID- 29374368
TI  - Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried
      Azithromycin Particles with L-Leucine for Inhalation.
AB  - PURPOSE: Inhalation therapy is popular to treat lower respiratory tract
      infections. Azithromycin is effective against some bacteria that cause
      respiratory tract infections; but it has poor water solubility that may limit its
      efficacy when administrated as inhalation therapy. In this study, dry powder
      inhaler formulations were developed by co-spray drying azithromycin with L
      leucine with a purpose to improve dissolution. METHODS: The produced powder
      formulations were characterized regarding particle size, morphology, surface
      composition and in-vitro aerosolization performance. Effects of L-leucine on the
      solubility and in-vitro dissolution of azithromycin were also evaluated. RESULTS:
      The spray dried azithromycin alone formulation exhibited a satisfactory aerosol
      performance with a fine particle fraction (FPF) of 62.5 +/- 4.1%. Addition of L
      leucine in the formulation resulted in no significant change in particle
      morphology and FPF, which can be attributed to enrichment of azithromycin on the
      surfaces of composite particles. Importantly, compared with the spray-dried
      amorphous azithromycin alone powder, the co-spray dried powder formulations of
      azithromycin and L-leucine demonstrated a substantially enhanced in-vitro
      dissolution rate. Such enhanced dissolution of azithromycin could be attributed
      to the formation of composite system and the acidic microenvironment around
      azithromycin molecules created by the dissolution of acidic L-leucine in the co
      spray dried powder. Fourier transform infrared spectroscopic data showed
      intermolecular interactions between azithromycin and L-leucine in the co-spray
      dried formulations. CONCLUSIONS: We developed the dry powder formulations with
      satisfactory aerosol performance and enhanced dissolution for a poorly water
      soluble weak base, azithromycin, by co-spray drying with an amino acid, L
      leucine.

PMID- 29374369
TI  - The effects of hydraulic works and wetlands function in the Salado-River basin
      (Buenos Aires, Argentina).
AB  - Man-made activities exert great influences on fluvial ecosystems, with lowland
      rivers being substantially modified through agricultural land use and
      populations. The recent construction of drainage canals in the upper stretch of
      the Salado-River basin caused the mobilization of huge amounts of salts formerly
      stored in the groundwater. The main aim of this work was to analyze the effect of
      the discharges of those canals into the Salado-River water, under different
      hydrologic conditions, and the role of the wetlands and shallow lakes placed
      along the canals' system. Physicochemical variables were measured and water
      samples were taken during times of high water, mean flows, drought, and extreme
      drought. The environmental variables and the plankton development were related to
      the hydrologic regime and reached minimum values during floods because of low
      temperatures and dilution. Local effects on the water's ionic composition became
      pronounced during droughts because of groundwater input. Nutrient concentrations
      were mainly associated with point wastewater discharges. Conductivity, ion
      concentrations, total plankton biomass, and species richness increased in the
      Salado-River downstream site, after the canals' discharges. The artificial
      drainage system definitely promotes the incorporation of salts into the Salado
      River basin. In this scenario, a careful hydraulic management is needed to take
      into account this issue of secondary salinization that threatens the economic
      exploitation of the region. The wetlands present in this study acted as service
      environments not only helping to reduce salt, nutrient, and suspended-solid
      concentrations downstream but also contributing a plethora of species and
      plankton biomass into the Salado-River main course.

PMID- 29374370
TI  - Twitter Use in the Hematopoietic Cell Transplantation Community.
AB  - PURPOSE OF REVIEW: Social media has revolutionized the access and exchange of
      information in healthcare. The microblogging platform Twitter has been used by
      blood and marrow transplant physicians over the last several years with
      increasing enthusiasm. We review the adoption of Twitter in the transplant
      community and its implications on clinical care, education, and research. RECENT
      FINDINGS: Twitter allows instantaneous access to the latest research
      publications, developments at national and international meetings, networking
      with colleagues, participation in advocacy, and promoting available clinical
      trials. Additionally, Twitter serves as a gateway for resources dedicated to
      education and support for patients undergoing transplantation. We demonstrate the
      utilization and various applications in using Twitter among hematopoietic cell
      transplant healthcare professionals, patients, and other affiliated stakeholders.
      Professionalism concerns with clinician use of such social media platforms,
      however, also exist. Overall, Twitter has enhanced and increased the
      opportunities for engagement in the transplant community.

PMID- 29374372
TI  - Targeting the CACNA1A IRES as a Treatment for Spinocerebellar Ataxia Type 6.
AB  - We have discovered that the P/Q-type voltage-gated Ca2+ channel (VGCC) gene,
      CACNA1A, encodes both the alpha1A (Cav2.1) subunit and a newly recognized
      transcription factor, alpha1ACT, by means of a novel internal ribosomal entry
      site (IRES) within the alpha1A C-terminal coding region. alpha1ACT, when mutated
      with an expansion of the polyglutamine tract in the C-terminus, gives rise to
      spinocerebellar ataxia type 6 (SCA6). Because silencing of the entire CACNA1A
      gene would result in the loss of the essential Cav2.1 channel, the IRES
      controlling alpha1ACT expression is an excellent target for selective silencing
      of alpha1ACT as a therapeutic intervention for SCA6. We performed a high
      throughput screen of FDA-approved small molecules using a dual luciferase
      reporter system and identified ten hits able to selectively inhibit the IRES. We
      identified four main candidates that showed selective suppression of alpha1ACT
      relative to alpha1A in HEK cells expressing a native CACNA1A vector. We
      previously pursued another avenue of molecular intervention through miRNA
      silencing. We studied three human miRNAs (miRNA-711, -3191-5p, -4786) that would
      potentially bind to sequences within the CACNA1A IRES region, based on an miRNA
      prediction program. Only miRNA-3191-5p was found to selectively inhibit the
      translation of alpha1ACT in cells. We developed a hyperacute model of SCA6 in
      mice by injecting a pathogenic form of the IRES-mediated alpha1ACT (AAV9
      alpha1ACTQ33). Finally, we tested the effectiveness of the miRNA therapy by co
      expressing either control miRNA or miRNA-3191-5p and found that miRNA-3191-5p
      decreased the levels of alpha1ACTQ33 and prevented the hyperacute disease in
      mice. These studies provide the proof of principle that a therapy directed at
      selectively preventing alpha1ACT expression could be used to treat SCA6.

PMID- 29374371
TI  - Rethinking Antimicrobial Prophylaxis in the Transplant Patient in the World of
      Emerging Resistant Organisms-Where Are We Today?
AB  - PURPOSE OF REVIEW: The use of prophylactic antibiotics during the neutropenic
      period in hematopoietic stem cell transplantation has been the standard of care
      at most institutions for the past 20 years. We sought to review the benefits and
      risks of this practice. RECENT FINDINGS: Emerging data has highlighted the
      potential costs of antibacterial prophylaxis, from selecting for antibiotic
      resistance to perturbing the microbiome and contributing to increase risk for
      Clostridium difficile and perhaps graft-versus-host-disease, conditions which may
      lead to poorer outcomes. Though in many studies prophylactic antibiotics improved
      morbidity and mortality outcomes, the potential harms including antibiotic
      resistance, Clostridium difficile infection, and alterations of the gut
      microbiome should be considered. Future studies aimed to better risk-stratify
      patients and limit the use of broad-spectrum antibiotics are warranted.

PMID- 29374373
TI  - Utilization of stress testing for low-risk patients with chest discomfort in the
      emergency department.
AB  - BACKGROUND: The management of patients presenting to an emergency department with
      chest discomfort at low-risk for acute coronary syndrome represents a common
      clinical challenge. Such patients are often triaged to chest pain units for
      monitoring and cardiac stress testing for further risk stratification. METHODS:
      We conducted a retrospective study of 292 low-risk patients who presented to an
      emergency department with chest discomfort. We performed physician-adjudicated
      chart reviews of all patients with positive stress tests to assess downstream
      testing, subsequent coronary revascularization, and outcomes. RESULTS: Of the 292
      patients, 33 (11.3%) had stress tests positive for ischemia, and 12 (4.1%)
      underwent diagnostic cardiac catheterization. Of the 292 patients, 4 (1.4%)
      underwent coronary revascularization that may have resulted in a mortality
      benefit. CONCLUSION: These data suggest a very low yield of detecting clinically
      significant coronary disease with stress testing low-risk patients with chest
      discomfort in emergency department chest pain units.

PMID- 29374374
TI  - Constant iodine intake through the diet could improve hypothyroidism treatment: a
      case report.
AB  - Currently, hypothyroidism is usually treated only with drugs; patients are never
      told that they could regulate their levels of iodine with dietary recommendations
      in a complementary way. The objective of this work was to explore the effect of a
      constant iodine intake through the diet in a postmenopausal woman with
      subclinical grade II hypothyroidism, who also had mild hypercholesterolemia and
      obesity. Baseline anthropometric nutritional, pharmacological, and habit data
      were obtained, then the woman was scheduled for 1 month a diet in which she was
      provided food naturally containing iodine, so that the recommended requirements
      (iodine 150 MUg/day) were met. All the information about which foods contain this
      mineral was supplied and explained to the patient. This diet was also designed to
      help her to gradually lose weight, and was more balanced and closer to the
      nutritional recommendations. The results obtained in this work were satisfactory,
      having achieved improved blood levels of thyroid-stimulating hormone (1.78
      MUIU/mL) and reduced total cholesterol levels (198 mg/dL). Statement of
      hypercholesterolemia was demoted. In addition, a significant improvement in
      relation to weight and body volume was reached (body mass index fell from 30.13
      to 28.5 kg/m2), an important fact since it has impacted the overall well-being of
      the patient. In conclusion, it was demonstrated that a constant iodine intake
      through the diet for this patient with grade II hypothyroidism was very
      effective, and therefore, this aspect should be also considered during
      hypothyroidism treatment.

PMID- 29374375
TI  - Geochemical characteristics of n-alkanes and isoprenoids in coal seams from Zhuji
      coal mine, Huainan coalfield, China, and their relationship with coal-forming
      environment.
AB  - Ten coal seams in Upper Shihezi Formation, Lower Shihezi Formation, and Shanxi
      Formation from the Zhuji mine, Huainan coalfield, China, were analyzed for n
      alkanes and isoprenoids (pristine and phytane) using gas chromatography-mass
      spectrometry (GC-MS), with an aim of reconstructing the coal-forming plants and
      depositional environments along with organic carbon isotope analyses. The total n
      alkane concentrations ranged from 34.1 to 481 mg/kg. Values of organic carbon
      isotope (delta13Corg) ranged from - 24.6 to - 23.70/00. The calorific value
      (Qb,d), maximum vitrinite reflectance (Romax), proximate, and ultimate analysis
      were also determined but showed no correlation with n-alkane concentrations.
      Carbon Preference Index (CPI) values ranged from 0.945 to 1.30, suggesting no
      obvious odd/even predominance of n-alkane. The predominance of C11 and C17 n
      alkanes implied that the coal may be deposited in the fresh and mildly brackish
      environment. According to the contrary changing trend of pristine/phytane (Pr/Ph)
      ratio and boron concentrations, Pr/Ph can be used as an indicator to reconstruct
      the marine transgression-regression in sedimentary environment of coal formation.
      The influence of marine transgression may lead to the enrichment of pyrite sulfur
      in the coal seam 4-2. C3 plants (- 32 to - 210/00) and marine algae (- 23 to -
      160/00) were probably the main coal-forming plants in the studied coal seams. No
      correlation of the n-alkane concentration and redox condition of the depositional
      environment with organic carbon isotope composition were found.

PMID- 29374376
TI  - Rhizospheric effects on the microbial community of e-waste-contaminated soils
      using phospholipid fatty acid and isoprenoid glycerol dialkyl glycerol tetraether
      analyses.
AB  - We performed the study of rhizospheric effects on soil microbial community
      structure, including bacteria, fungi, actinomycete, and archaea, at an electronic
      waste (e-waste) recycling site by analyzing the phospholipid fatty acid (PLFA)
      and isoprenoid glycerol dialkyl glycerol tetraether (GDGT) contents. By comparing
      PLFA and isoprenoid GDGT profiles of rhizospheric and surrounding bulk soils of
      11 crop species, we observed distinct microbial community structures. The total
      PLFA concentration was significantly higher in rhizospheric soils than in non
      rhizospheric soils, whereas no obvious difference was found in the total
      isoprenoid GDGT concentrations. The microbial community structure was also
      different, with higher ratios of fungal-to-bacterial PLFAs (F/B) and lower
      relative abundance of Gram-positive bacteria in rhizospheric soils. The extent of
      rhizospheric effects varied among plant species, and Colocasia esculenta L. had
      the greatest positive effects on the total microbial biomass. Dissolved organic
      carbon and pH were the main environmental factors affecting the microbial
      community represented by PLFAs, while the archaeal community was influenced by
      copper and zinc in all soils. These results offer a comprehensive view of
      rhizospheric effects on microbes in heavy metal and persistent organic pollutant
      co-contaminated soil, and provide fundamental knowledge regarding microbial
      ecology in e-waste-contaminated soils.

PMID- 29374377
TI  - Toxicity of aqueous mixture of phenol and chlorophenols upon photosensitized
      oxidation initiated by sunlight or vis-lamp.
AB  - It is well established that aquatic wildlife in marine and freshwater of the
      European Union is exposed to natural and synthetic endocrine disruptor compounds
      (EDCs) which are able to interfere with the hormonal system causing adverse
      effects on the intact physiology of organisms. The traditional wastewater
      treatment processes are inefficient on the removal of EDCs in low concentration.
      Moreover, not only the efficiency of treatment must be considered but also
      toxicological aspects. Taking into account all these aspects, the main goal of
      the study was to investigate the photochemical decomposition of hazardous
      phenolic compounds under simulated as well as natural sunlight from the toxicity
      point of view. The studies were focused on photodegradation of 2,4-dichlorophenol
      as well as mixture of phenol, 2-chlorophenol and 2,4-dichlorophenol.
      Photosensitized oxidation process was carried out in homogeneous and
      heterogeneous system. V. fischeri luminescence inhibition was used to determine
      the changes of toxicity in mixture during simulated and natural irradiation. The
      photodegradation was carried out in three kinds of water matrix; moreover, the
      influence of presence of inorganic matter on the treatment process was
      investigated. The experiments with natural sunlight proved applicability of
      photosensitive chitosan for visible-light water pollutant degradation. The
      results of toxicity investigation show that using photosensitive chitosan for
      visible-light, the toxicity of reaction mixture towards V. fischeri has
      significantly decreased. The EC50 was found to increase over the irradiation
      time; this increase was not proportional to the transformation of the parent
      compounds.

PMID- 29374378
TI  - Protective effect of melatonin on cadmium-induced changes in some maturation and
      reproductive parameters of female Prussian carp (Carassius gibelio B.).
AB  - The aim of this study was to determine whether melatonin (Mel), which is a known
      antioxidant and free radical scavenger, could perform the role of a preventive
      agent against the toxic effects of cadmium (Cd2+) on mortality, fish growth,
      gonadosomatic index (GSI), luteinizing hormone (LH) secretion, the response to
      hormonal stimulation of spawning, and also tissue accumulation of Cd in Prussian
      carp females. These females received melatonin implants and were exposed to 0.4
      or 4.0 mg/L of Cd (as CdCl2.2.5H2O) over either a 5- or 3-month period, followed
      by further 2 months of purification in clear water. Negative changes caused by
      exposure to cadmium in the water were as follows: higher fish mortality, lower
      body weight, increased accumulation of cadmium in the brain and ovary, lowered
      GSI, impaired spontaneous LH secretion during exposure, and impaired LH secretion
      during stimulation of spawning. All of these effects were observed in the group
      of fish exposed to 0.4 and/or 4.0 mg Cd/L but did not occur or were less
      pronounced in the groups exposed to cadmium in the presence of melatonin released
      from the implants. During depuration, in the group of fish which had been exposed
      to the highest Cd concentration, we observed a significant improvement in fish
      survival rate, body growth, inhibition of further cadmium accumulation in
      tissues, and gradual return of spontaneous LH secretion as well as normalization
      of the GSI value to the control group levels. In conclusion, these findings
      indicate that melatonin can be a preventive agent for some toxic effects on fish
      reproduction induced by environmental cadmium contamination.

PMID- 29374379
TI  - Effects of dissolved organic matter leaching from macrophyte litter on black
      water events in shallow lakes.
AB  - In recent years, the black water phenomenon has become an environmental event in
      eutrophic shallow lakes in China, leading to deterioration of lake ecosystems and
      potable water crises. Decomposition of macrophyte debris has been verified as a
      key inducement for black water events. In this study, the effects of the
      decomposition of dissolved organic matter (Kottelat et al., WASP 187:343-351,
      2008) derived from macrophyte leachate on the occurrence of black water events
      are investigated to clarify the detailed mechanisms involved. Results show that
      dissolved organic matter (DOM) is composed of a trace of chromophoric DOM and
      mostly non-chromophoric dissolved organic matter (CDOM). DOM decomposition is
      accompanied by varied concentration of CDOM components, generation of organic
      particles, and increased microbial concentrations. These processes increase water
      chroma only during initial 48 h, so the intensified water color cannot be
      maintained by DOM decomposition alone. During DOM decomposition, microorganisms
      first consume non-CDOM, increasing the relative CDOM concentration and turning
      the water color to black (or brown). Simultaneously, tryptophan and aromatic
      proteins, which are major ingredients of CDOM, enhance UV light absorption,
      further aggravating the macroscopic phenomenon of black color. Our results show
      that DOM leached from decayed macrophytes promotes or even triggers the
      occurrence of black water events and should be taken more seriously in the
      future.

PMID- 29374380
TI  - Cooking oil fume-derived PM2.5 induces apoptosis in A549 cells and MAPK/NF
      kB/STAT1 pathway activation.
AB  - Cooking oil fumes (COFs) are the major sources of indoor air pollution in Asia.
      It is well known that alveolar cells are key participants in the development of
      respiratory system; however, it still remains unknown whether alveolar cells are
      affected by COFs. Therefore, the present study investigated the effects of COFs
      on alveolar cells (A549 cells) and illuminated its apoptotic mechanism in
      response to COF-PM2.5 exposure. When A549 cells were exposed to COF-PM2.5, cell
      viability was substantially decreased, while the generation of ROS increased, and
      LDH levels and CCK-8 levels gradually changed within a dose-dependent manner. The
      nitrite concentration in the supernatants was augmented, while the SOD activity
      and GSH recycling were decreased upon COF-PM2.5. Moreover, COF-PM2.5 treatment
      increased mRNA levels of COX-2, inducible NO synthase, and TNF-alpha, and Elisa
      assay suggested that secretory proteins IL-6 and TNF-alpha were also increased.
      Furthermore, the Bax/Bcl-2 mRNA ratio was increased, and cleaved caspase-3
      protein was activated in the A549 cells. Strikingly, COF-PM2.5 induced the
      phosphorylation of STAT1 at Tyr701/Ser727 and activation of NF-kB and ERK1/2,
      p38, and JNK of the MAPK pathway. In short, our study suggested that COF-PM2.5
      resulted in inflammation, apoptosis, and cell damage in A549 cells, which might
      be modulated via the activation of MAPK/NF-kB/STAT1 pathway.

PMID- 29374382
TI  - Zinc Supplementation Does Not Affect Glucagon Response to Intravenous Glucose and
      Insulin Infusion in Patients with Well-Controlled Type 2 Diabetes.
AB  - Glucagon dysregulation is an essential component in the pathophysiology of type 2
      diabetes. Studies in vitro and in animal models have shown that zinc co-secreted
      with insulin suppresses glucagon secretion. Zinc supplementation improves blood
      glucose control in patients with type 2 diabetes, although there is little
      information about how zinc supplementation may affect glucagon secretion. The
      objective of this study was to evaluate the effect of 1-year zinc supplementation
      on fasting plasma glucagon concentration and in response to intravenous glucose
      and insulin infusion in patients with type 2 diabetes. A cross-sectional study
      was performed after 1-year of intervention with 30 mg/day zinc supplementation or
      a placebo on 28 patients with type 2 diabetes. Demographic, anthropometric, and
      biochemical parameters were determined. Fasting plasma glucagon and in response
      to intravenous glucose and insulin infusion were evaluated. Patients of both
      placebo and supplemented groups presented a well control of diabetes, with mean
      values of fasting blood glucose and glycated hemoglobin within the therapeutic
      goals established by ADA. No significant differences were observed in plasma
      glucagon concentration, glucagon/glucose ratio or glucagon/insulin ratio fasting,
      after glucose or after insulin infusions between placebo and supplemented groups.
      No significant effects of glucose or insulin infusions were observed on plasma
      glucagon concentration. One-year zinc supplementation did not affect fasting
      plasma glucagon nor response to intravenous glucose or insulin infusion in well
      controlled type 2 diabetes patients with an adequate zinc status.

PMID- 29374381
TI  - Phonological and graphotactic influences on spellers' decisions about consonant
      doubling.
AB  - Even adults sometimes have difficulty choosing between single- and double-letter
      spellings, as in spinet versus spinnet. The present study examined the
      phonological and graphotactic factors that influence adults' use of single versus
      double medial consonants in the spelling of nonwords. We tested 111 adults from a
      community sample who varied widely in spelling ability. Better spellers were more
      affected than less good spellers by phonological context in that they were more
      likely to double consonants after short vowels and less likely to double
      consonants after long vowels. Although descriptions of the English writing system
      focus on the role of phonology in determining use of single versus double
      consonants, participants were also influenced by graphotactic context. There was
      an effect of preceding graphotactic context, such that spellers were less likely
      to use a double consonant when they spelled the preceding vowel with more than
      one letter than when they spelled it with one letter. There was also an effect of
      following graphotactic context, such that doubling rate varied with the letters
      that the participant used at the end of the nonword. These graphotactic
      influences did not differ significantly in strength across the range of spelling
      ability in our study. Discussion focuses on the role of statistical learning in
      the learning of spelling patterns, especially those patterns that are not
      explicitly taught.

PMID- 29374383
TI  - Festina Lente-a curiously apt aphorism for Interventional Cardiac
      Electrophysiology in 2018.

PMID- 29374384
TI  - A phase II study of tipifarnib and gemcitabine in metastatic breast cancer.
AB  - Background Tipifarnib is an orally active, competitive inhibitor of
      farnesyltransferase which has shown encouraging signs of activity either alone or
      when combined with other agents. Clinical studies of tipifarnib in combination
      with anti-estrogen therapy have yielded disappointing results. In contrast,
      tipifarnib appears to be synergistic in combination with anthracycline based
      chemotherapy. Here we report the results of the first prospective phase II trial
      evaluating the efficacy of the novel combination of tipifarnib and gemcitabine in
      the treatment of metastatic breast cancer. Patients and Methods 30 postmenopausal
      women with metastatic breast cancer were treated on a 21-day cycle with
      tipifarnib 300 mg PO twice daily from days 1 through 14. Gemcitabine was
      administered intravenously at a dose of 1000 mg/m2 on days 1 and 8. Patients were
      treated until disease progression or unacceptable toxicity. Results There was one
      complete response and four partial responses yielding an objective response rate
      of 16.7%. Median progression-free survival and overall survival was 2.5 months
      (95% confidence interval: 1.6-5.7 months) and 13.1 months (95% confidence
      interval: 9.1-20.6 months), respectively. 40% of patients experienced grade 4
      neutropenia in this study. Conclusion The combination of tipifarnib and
      gemcitabine is not well tolerated with high rates of myelosuppression and is not
      more effective than gemcitabine monotherapy in the treatment of metastatic breast
      cancer.

PMID- 29374386
TI  - Rearranging Deck Chairs on a Sinking Ship? : Some Reflections on Ethics and
      Reproduction Looking Back at 2017 and Ahead at 2018.

PMID- 29374385
TI  - Cyclospora cayetanensis infections among diarrheal outpatients in Shanghai: a
      retrospective case study.
AB  - Cyclospora cayetanensis is a foodborne and waterborne pathogen that causes
      endemic and epidemic human diarrhea worldwide. A few epidemiological studies
      regarding C. cayetanensis infections in China have been conducted. During 2013, a
      total of 291 stool specimens were collected from patients with diarrhea at a
      hospital in urban Shanghai. C. cayetanensis was not detected in any of the stool
      specimens by traditional microscopy, whereas five stool specimens (1.72%, 5/291)
      were positive by PCR. These positive cases confirmed by molecular technology were
      all in the adult group (mean age 27.8 years; 2.94%, 5/170) with watery diarrhea.
      Marked infection occurred in the rainy season of May and July. Sequence and
      phylogenetic analyses of the partial 18S rRNA genes of C. cayetanensis isolated
      showed intra-species diversity of this parasite. This study showed, for the first
      time, that C. cayetanensis is a pathogen in outpatients with diarrhea in
      Shanghai, albeit at a low level. However, the transmission dynamics of this
      parasite in these patients remain uncertain.

PMID- 29374387
TI  - Delineation of two intracranial areas and the perpendicular intracranial width is
      sufficient for intracranial volume estimation.
AB  - OBJECTIVES: The aim of the present study is to determine if the delineation of
      one or two optimally chosen intracranial areas (ICA) is enough to achieve
      adequate estimates of intracranial volume (ICV) in magnetic resonance imaging.
      METHODS: The correlations of 62 fully delineated ICVs with four types of ICV
      estimates were calculated. The estimate types were: (1) a single midsagittal ICA,
      (2) single ICA multiplied by the intracranial width perpendicular to the ICA, (3)
      sum of two ICAs multiplied by the perpendicular intracranial width and (4) shape
      preserving piecewise cubic interpolation using two ICAs. For methods 2-4, the
      fully delineated ICVs were randomly separated into an evaluation and a validation
      set of equal size. Method 1 was validated against all of the fully delineated
      ICVs. RESULTS: Estimates from method 1 had a Pearson correlation of 0.904 with
      fully delineated ICV. For method 2, the correlation was 0.986 when delineating
      the sagittal ICA at 31% of the sagittal intracranial width. For methods 3 and 4,
      the correlations were both 0.997 when delineating the sagittal ICAs at 17.5 and
      64% and at 12 and 64% respectively. CONCLUSIONS: Delineation of two specific
      intracranial areas is sufficient for intracranial volume estimation. MAIN
      MESSAGES: * Delineation of two specific intracranial areas is sufficient for
      intracranial volume estimation. * The estimates had a Pearson correlation of
      0.997 with intracranial volume. * The estimation should take no more than 5 min.

PMID- 29374388
TI  - Morphological Description of the Immature Stages of Nyssomyia umbratilis (Ward &
      Frahia) (Diptera: Psychodidae: Phlebotominae), the Main Vector of Leishmania
      guyanensis Floch (Kinetoplastida: Trypanosomatidae) in the Brazilian Amazon
      Region.
AB  - Nyssomyia umbratilis (Ward & Frahia) is the main vector of Leishmania guyanensis
      in the Brazilian Amazon region, where it is widely distributed. Studies have
      hypothesized that this phlebotomine is part of a cryptic species complex,
      spatially delimited by the Amazonian river systems, and with different
      transmission potential of L. guyanensis. In the present study, the immature
      stages of N. umbratilis are described from laboratory-reared specimens
      originating from the states of Amazonas and Para, Brazil. Based on scanning
      electron and optical microscopy examinations, fine morphological structures
      (eggshell, setae, and mouthparts of larvae and pupae) are presented. A new form
      of sandfly pupae sexing (non-invasive) is also provided. The correct
      identification of insect is extremely important for the epidemiology of certain
      diseases. However, only the morphological characters of adult can be insufficient
      to separate accurately the closely related species. It is expected that the
      present description may contribute to solve the taxonomic problem involving N.
      umbratilis.

PMID- 29374389
TI  - Community action research track: Community-based participatory research and
      service-learning experiences for medical students.
AB  - Community-based participatory research (CBPR) and service-learning are unique
      experiential approaches designed to train medical students how to provide
      individualized patient care from a population perspective. Medical schools in the
      US are required to provide support for service-learning and community projects.
      Despite this requirement, few medical schools offer structured service-learning.
      We developed the Community Action Research Track (CART) to integrate population
      medicine, health promotion/disease prevention and the social determinants of
      health into the medical school curriculum through CBPR and service-learning
      experiences. This article provides an overview of CART and reports the program
      impact based on students' participation, preliminary evaluations and
      accomplishments. CART is an optional 4-year service-learning experience for
      medical students interested in community health. The curriculum includes a
      coordinated longitudinal program of electives, community service-learning and
      lecture-based instruction. From 2009-2015, 146 CART students participated.
      Interests in public health (93%), community service (73%), primary care (73%),
      CBPR (60%) and community medicine (60%) were the top reasons for enrolment.
      Significant improvements in mean knowledge were found when measuring the
      principles of CBPR, levels of prevention, determining health literacy and patient
      communication strategies (all p's < 0.05). Most students (73%) were satisfied
      with CART. Projects were disseminated by at least 65 posters and four oral
      presentations at local, national and international professional meetings. Six
      manuscripts were published in peer-reviewed journals. CART is an innovative
      curriculum for training future physicians to be community-responsive physicians.
      CART can be replicated by other medical schools interested in offering a
      longitudinal CBPR and service-learning track in an urban metropolitan setting.

PMID- 29374390
TI  - Multivariate normal maximum likelihood with both ordinal and continuous
      variables, and data missing at random.
AB  - A novel method for the maximum likelihood estimation of structural equation
      models (SEM) with both ordinal and continuous indicators is introduced using a
      flexible multivariate probit model for the ordinal indicators. A full information
      approach ensures unbiased estimates for data missing at random. Exceeding the
      capability of prior methods, up to 13 ordinal variables can be included before
      integration time increases beyond 1 s per row. The method relies on the axiom of
      conditional probability to split apart the distribution of continuous and ordinal
      variables. Due to the symmetry of the axiom, two similar methods are available. A
      simulation study provides evidence that the two similar approaches offer equal
      accuracy. A further simulation is used to develop a heuristic to automatically
      select the most computationally efficient approach. Joint ordinal continuous SEM
      is implemented in OpenMx, free and open-source software.

PMID- 29374391
TI  - Extracellular Vesicles As miRNA Nano-Shuttles: Dual Role in Tumor Progression.
AB  - Tumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer,
      interacting with target cells of the tumor microenvironment, such as fibroblasts,
      immune and endothelial cells. EVs can modulate tumor progression, angiogenic
      switch, metastasis, and immune escape. These vesicles are nano-shuttles
      containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs
      contained in extracellular vesicles (EV-miRNAs) are disseminated in the
      extracellular space and are able to influence the expression of target genes with
      either tumor suppressor or oncogenic functions, depending on both parental and
      target cells. Metastatic cancer cells can balance their oncogenic potential by
      expressing miRNAs with oncogenic function, whilst exporting miRNAs with tumor
      suppressor roles out of the cells. Importantly, treatment of cancer cells with
      specific natural and chemical compounds could induce the elimination of miRNAs
      with oncogenic function, thereby reducing their aggressiveness. In this review,
      we discuss the mechanisms by which EV-miRNAs, acting as miRNAs with oncogenic or
      tumor suppressor functions, could contribute to cancer progression.

PMID- 29374393
TI  - Ultrasound follow-up of an unusual giant urinoma in a newborn.
AB  - Urinoma, defined as an encapsulation of urine caused by urine extravasation into
      the perirenal space either through rupture of a calyceal fornix or a tear in the
      renal parenchyma, is an uncommon finding in prenatal diagnosis and the neonatal
      period. Urinoma can be associated with any urinary tract obstruction, or, as
      reported in several published cases, related to vesicoureteral reflux, kidney
      dysplasia, or complication arising during amniocentesis. We report on a newborn
      with a perinatal urinoma, with initial slight corpusculated fluid associated with
      nonobstructive and nonrefluxing megaureter, and no signs of kidney dysplasia.
      Close sonography follow-up of the urinoma allowed complex differential diagnoses,
      including cystic, septated, and solid perirenal masses, due to dissimilar and
      peculiar ultrasound images during urinoma evolution stages.

PMID- 29374392
TI  - p53 expression and subcellular survivin localization improve the diagnosis and
      prognosis of patients with diffuse astrocytic tumors.
AB  - PURPOSE: Diffuse astrocytic tumors are the most frequently occurring primary
      central nervous system (CNS) tumors. Their histological sub-classification into
      diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GB) is
      challenging and the available prognostic factors are limited to age and tumor
      subtype. Biomarkers that may improve the histological sub-classification and/or
      serve as prognostic factors are, therefore, urgently needed. The relationship
      between survivin and p53 in diffuse astrocytic tumor progression and survival is
      currently unclear. Here, we aimed to assess the relevance of these proteins in
      the accuracy of the histological sub-classification of these tumors and their
      respective treatment responses. METHODS: One hundred and thirty-three formalin
      fixed paraffin-embedded diffuse astrocytic tumor samples were included. The tumor
      samples were histologically reviewed and subsequently assessed for p53 and
      survivin expression and the presence of the IDH R132H mutation by
      immunohistochemistry. p53 expression levels and survivin subcellular localization
      patterns were correlated with histological classification and clinical outcome.
      RESULTS: We found that age and histological subtype were the only features with a
      prognostic impact. In addition, we found that high p53 expression levels and a
      nuclear survivin localization correlated with the AA subtype, whereas cytoplasmic
      survivin localization correlated with the GB subtype. We also found that patients
      carrying tumors with a high cytoplasmic survivin expression, a high nuclear
      survivin expression or a high p53 expression, and who did not receive
      radiotherapy, exhibited poorer short-term and long-term overall survival rates.
      CONCLUSIONS: Our data suggest that subcellular survivin localization and p53
      expression may be employed as valuable tools to improve the accuracy of the
      histological sub-classification of diffuse astrocytic tumors. Patients whose
      tumors overexpress these proteins may benefit from radiotherapy, irrespective age
      and/or histological classification.

PMID- 29374394
TI  - Isolated fallopian tube metastasis from colorectal cancer: ultrasonographic
      features.
AB  - We present here the first-reported case of tubal metastasis from colorectal
      cancer diagnosed by a preoperative pelvic ultrasound. A 53-year-old woman
      suffering from vaginal discharge was referred to us 2 years after she underwent a
      partial colectomy for adenocarcinoma. The pelvic ultrasound examination revealed
      a right pelvic mass of 52 * 24 * 38 mm, independent of the right ovary, which was
      apparently unaffected. A right salpingo-oophorectomy was performed and the
      definitive histopathology examination showed a recurrence of the initial
      adenocarcinoma with a right tubal metastasis. The eventuality of such an unusual
      site of metastasis should be remembered.

PMID- 29374395
TI  - Ultrasonographic findings of shoulder teno-muscular structures in symptomatic and
      asymptomatic dogs.
AB  - PURPOSE: B-mode sonographic evaluation of shoulder joint in dogs provides
      qualitative information concerning mainly tendon and muscles structures. Although
      the sonographic findings of tenomuscular lesions have been described previously,
      their frequency in symptomatic and asymptomatic patients has not been reported
      yet. Aim of the study was to describe and compare qualitative ultrasonographic
      findings of shoulder joint in clinically symptomatic and asymptomatic dogs and to
      speculate which lesions might be considered major responsible for lameness.
      METHODS: Fifty-two dogs with shoulder lameness and 58 asymptomatic dogs (both
      with unremarkable radiographic findings) underwent ultrasonographic B-mode
      examination of the scapulohumeral joint. Lesions detected were recorded and
      statistically compared between groups. RESULTS: Significant differences between
      groups were observed for the number of ultrasonographic abnormalities detected
      and for fluid accumulation, biceps brachii tendon (BT) lesions and bone surface
      irregularities. Sonography was considered useful for the determination of lesions
      absence and for the detection of BT lesions, fluid accumulation, muscle
      lacerations and bone surface irregularities. The odds for symptomatic dogs were
      greater than for asymptomatic patients to ultrasonographically diagnose BT
      lesions, fluid accumulation and bone surface irregularities. CONCLUSIONS:
      Ultrasound has proven to be a useful tool in the evaluation of
      tenomusculoskeletal structures of shoulder in dogs with unremarkable radiographic
      findings. Our results suggest that ultrasonography is useful in the diagnosis of
      tendon abnormalities, fluid accumulation, muscle lacerations and bone surface
      irregularities as potential contributors to shoulder lameness in dogs.

PMID- 29374396
TI  - Thyroid adenolipoma: a case report.
AB  - Generally, small quantities of adipose tissue is present in the thyroid gland.
      The adenolipoma of the thyroid gland is considered a rare finding. It consists in
      a benign, encapsulated neoplasm composed of mature adipose tissue and glandular
      elements. We report a case of a 71 year-old female patient presenting with
      swelling of the anterior neck and history of airway obstruction. Ultrasound (US)
      examination showed a bulky multinodular goiter which caused dislocation and
      compression of the trachea. The scans performed at the level of the isthmic
      region showed the presence of a hyperechoic oval formation with a homogeneous
      echostructure and regular contours; these characteristics suggested the
      lipomatous nature of the nodule. The patient was subsequently subjected to a
      Computer Tomography (CT) of the neck for a pre-operative balance of the goitre
      and to exclude extra-thyroid pathologies. The CT scan confirmed the sonographic
      findings, and the probable adipose nature of the isthmic formation. After the
      patient has been subjected to total thyroidectomy and histological examination
      confirmed the diagnosis of adenolipoma.

PMID- 29374397
TI  - A novel method for creating custom shaped ballistic gelatin trainers using
      plaster molds.
AB  - Simulation based procedural training is an effective and frequently used method
      for teaching vascular access techniques which often require commercial trainers.
      These can be prohibitively expensive, which allows for homemade trainers made of
      gelatin to be a more cost-effective and attractive option. Previously described
      trainers are often rectangular with a flat surface that is dissimilar to human
      anatomy. We describe a novel method to create a more anatomically realistic
      trainer using ballistic gelatin, household items, and supplies commonly found in
      an emergency department such as the plaster wrap typically used to make splints.

PMID- 29374398
TI  - Iatrogenic intratendinous ganglion cyst of the extensor digitorum tendon
      following intravenous cannulation.
AB  - Peripheral venous cannulation is one of the most commonly performed medical
      procedures in hospital medicine. The dorsal metacarpal veins are typically used
      for cannulation as they are easily accessible. We present the first case of an
      iatrogenic intratendinous ganglion cyst of the extensor digitorum tendon of the
      middle finger following intravenous cannulation.

PMID- 29374399
TI  - Sonographic evaluation of kidney echogenicity and morphology among HIV sero
      positive adults at Lagos University Teaching Hospital.
AB  - AIM: To evaluate the role of kidney echogenicity and morphology in the diagnosis
      of human immunodeficiency virus-associated nephropathy (HIVAN). SUBJECTS AND
      METHODS: In the cross-sectional study, a sample of 340 anti-retroviral therapy
      (ART)-naive AIDS patients underwent laboratory CD4+ count, serum creatinine
      determination and sonographic renal echogenicity grading and size measurement.
      Rounded kidneys were described as bulbous while bean-shaped kidneys were
      described as reniform; echogenicity was categorized into grades 0, 1, 2 and 3.
      Kidney length, width, thickness and volume were measured in HIVAN and control
      groups. RESULTS: Mean age of the population was 42.7 +/- 9.4 years; 87.4% had
      HIVAN. Mean CD4+ count, serum creatinine and GFR for HIVAN patients were 153.1 +/
      103.2 cells/mm3, 218.4 +/- 147.4 mmol/L and 50.1 +/- 23.6 mL/min/1.73 m2 for
      males and 121.9 +/- 91.0 cells/mm3, and 222.0 +/- 150.4 mmol/L and 39.3 +/- 20.6
      mL/min/1.73 m2 for females, respectively; control subjects and non-HIVAN patients
      had grade 0 renal echogenicity; 56.9% of HIVAN patients had echogenicity grade 3;
      5.3% had kidney length < 10 cm; 73.9% had bulbous kidneys; the kidney was
      significantly wider and thicker in HIVAN (p < 0.05). CONCLUSION: Sonographic
      evaluation of renal echogenicity and morphology can reliably predict HIVAN
      diagnosis. Apathy to screening and late presentation were high while HIV/AIDS
      remains an important public health problem in the city of Lagos. Unilateral
      reduction in kidney size could be a major sequela of AIDS while sonographic
      measurement of absolute kidney length appears inadequate in the evaluation of
      AIDS patients with nephropathy.

PMID- 29374400
TI  - Three-dimensional echocardiography for the assessment of left ventricular
      geometry and papillary muscle morphology in hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HC) is characterized by left ventricular
      (LV) hypertrophy and associated with papillary muscle (PM) abnormalities. The aim
      of this study was to evaluate the utility of three-dimensional echocardiography
      (3DE) for the geometric assessment of LV hypertrophy and PM morphology. METHODS:
      The study included 24 patients with an established diagnosis of HC and 31 healthy
      controls. 3DE was performed using an iE33 or EPIQ 7C ultrasound system with an X5
      1 transducer. QLAB software was used for the 3D analysis of LV wall thickness
      (LVWT) and PM morphology and hypertrophy; the number and cross-sectional area
      (CSA) of anterolateral and posteromedial PMs; and the presence of bifid or
      accessory PMs. RESULTS: Patients with HC had a larger LVWT compared to controls
      in all segments (p < 0.001), and LVWT was largest in the midventricular septal
      segment (2.12 +/- 0.68 cm). The maximum LVWT followed a spiral pattern from the
      LV base to the apex. The CSA of both anterolateral and posteromedial PMs was
      larger in patients with HC than in controls (1.92 vs. 1.15 cm2; p = 0.001 and
      1.46 vs. 1.08 cm2; p = 0.033, respectively). The CSA of the posteromedial PM was
      larger in patients with LVOT obstruction than in those without (2.64 vs 1.16 cm2,
      p = 0.021). CONCLUSIONS: 3DE allows the assessment of LV geometry and PM
      abnormalities in patients with HC. 3DE demonstrated that the maximum hypertrophy
      was variable and generally located in a spiral from the LV base to the apex.

PMID- 29374401
TI  - Inter-rater and intra-rater reliability of the airway diameter measured by
      sonography.
AB  - INTRODUCTION: Sonography has gained a broad field of applications in current
      anesthetic practice. During airway management, it could have an important role,
      because it allows real-time measurement of anatomical aspects and a functional
      evaluation with high safety profile. However, assessment of the reliability and
      precision of these measurements is critical if sonography is used as a clinical
      diagnostic tool. The aim of the study was to estimate inter-rater and intra-rater
      reliability of the airway diameter measured by sonography in heathy volunteers.
      METHODS: We conducted a cross-sectional study during 2015 on healthy adult
      volunteers. Using sonography, transverse internal diameter of subglottic space
      was measured twice by two blinded sonographers. RESULTS: Agreement was classified
      as very good for intra-rater measurements (ICC = 0.84) and good for the inter
      rater measurements (ICC = 0.71). The 95% CI of agreement limits for the intra
      rater measurements were inferior to those for the inter-rater measurements.
      CONCLUSIONS: Ultrasound measurement is a reliable and precise method to measure
      the internal subglottic diameter of the airway. Ultimately, this method may
      provide clinicians valuable information regarding airway diameter in adults and
      may help to guide treatment options.

PMID- 29374402
TI  - Urgent need to apply a common language in image-guided thermal ablations.

PMID- 29374403
TI  - Detection of carious lesions utilizing depolarization imaging by polarization
      sensitive optical coherence tomography.
AB  - As dental caries is one of the most common diseases, the early and noninvasive
      detection of carious lesions plays an important role in public health care.
      Optical coherence tomography (OCT) with its ability of depth-resolved, high
      resolution, noninvasive, fast imaging has been previously recognized as a
      promising tool in dentistry. Additionally, polarization sensitive imaging
      provides quantitative measures on the birefringent tissue properties and can be
      utilized for imaging dental tissue, especially enamel and dentin. By imaging
      three exemplary tooth samples ex vivo with proximal white spot, brown spot, and
      cavity, we show that the combination of polarization sensitive OCT and the degree
      of polarization uniformity (DOPU) algorithm is a promising approach for the
      detection of proximal carious lesions due to the depolarization contrast of
      demineralized tissue. Furthermore, we investigate different sizes of the DOPU
      evaluation kernel on the resulting contrast and conclude a suitable value for
      this application. We propose that DOPU provides an easy to interpret image
      representation and appropriate contrast for possible future screening
      applications in early caries diagnostics.

PMID- 29374404
TI  - Scalable and massively parallel Monte Carlo photon transport simulations for
      heterogeneous computing platforms.
AB  - We present a highly scalable Monte Carlo (MC) three-dimensional photon transport
      simulation platform designed for heterogeneous computing systems. Through the
      development of a massively parallel MC algorithm using the Open Computing
      Language framework, this research extends our existing graphics processing unit
      (GPU)-accelerated MC technique to a highly scalable vendor-independent
      heterogeneous computing environment, achieving significantly improved performance
      and software portability. A number of parallel computing techniques are
      investigated to achieve portable performance over a wide range of computing
      hardware. Furthermore, multiple thread-level and device-level load-balancing
      strategies are developed to obtain efficient simulations using multiple central
      processing units and GPUs.

PMID- 29374405
TI  - Shortwave-infrared Raman spectroscopic classification of water fractions in
      articular cartilage ex vivo.
AB  - Water loss is an early onset indicator of osteoarthritis. Although Raman
      spectroscopy (RS) holds the potential for measurement of cartilage hydration, the
      knowledge of Raman OH-stretch bands of biological tissue is very limited. We
      assesed here the sensitivity of RS to identify and classify water types in the
      cartilage. Raman spectrum measurements over the high wavenumber range were
      employed to identify different water fractions in articular cartilage. Raman
      spectra were collected from wet and sequentially dehydrated cartilage along with
      pure collagen type II and chondroitin sulfate standards. OH-stretch band of
      cartilage is dominated by mobile water, up to 95% of total intensities. We
      identified six peaks in cartilage spectrum using second-derivative analysis:
      peaks at 3200 and 3650  cm-1 are associated with organic matrix (both collagen
      and proteglycan) and matrix-bound water molecules. Peaks at 3250, 3453, and 3630 
      cm-1 are associated with collagen and collagen-related water molecules, whereas
      the peak at 3520  cm-1 is associated with proteoglycan (PG) and PG-related water
      molecules. The current work is the first thorough analysis of the Raman OH
      stretch band of the cartilage and with the knowledge generated by this study, it
      may now be possible to study on cartilage hydration by RS.

PMID- 29374406
TI  - Minimum Residual Disease in Patients Post Radical Prostatectomy for Prostate
      Cancer: Theoretical Considerations, Clinical Implications and Treatment Outcome
AB  - Introduction: Minimal residual disease (MRD) remaining after curative therapy for
      prostate cancer has the potentialfor growth and can result in metastasis.
      Circulating prostate cells (CPCs) and bone marrow micro-metastasis (mM)could
      represent different types of MRD. We here determined; biochemical failure free
      survival rates; time to BF after10 years follow-up; and the presence of CPCs and
      mM in patients treated with radical prostatectomy (RP) for prostatecancer.
      Methods and Patients: One month after RP, blood and bone marrow were sampled for
      assessment of CPCsand mM. Cases were classified as: group A, CPC negative and mM
      negative; group B, CPC negative and mM positive;Group C, CPC positive and mM
      negative; and Group D, CPC positive and mM positive. Subjects were followed
      withserial determination of PSA levels, recording the time at which BF occurred
      defined as a serum PSA >0.2ng/ml. Afterten years of follow-up Kaplan-Meier
      survival curves were generated and the restricted mean survival time (RMST)
      foreach group calculated. Results: A total of 321 men participated, 140 in group
      A with survival of 92.7% (86.3 to 96.2),39 in group B with 55.8% (37.2 to 70.9);
      54 in group C with 6.41% (1.19 to 18.21) and 88 in group D with 4.96%(1.64to
      11.13%. The RMST (in years) were: group A, 9.47 (9.24 to 9.69); group B, 9.23
      (8.87 to 9.58); group C, 4.62 (4.46to 4.77); and group D, 3.57 (3.52 and 3.63) (p
      value<0.001 between groups: A versus C and D, B versus C and D).Conclusions: CPC
      positive men have more aggressive disease, with increased early failure; men who
      are only positivefor mM are at greater risk of late failure. These two forms of
      MRD represent different clinical entities with respect tobiochemical failure and
      could be used to guide clinical treatment decisions.

PMID- 29374407
TI  - Increased Risk of Penile Cancer among Men Working in Agriculture
AB  - Background: Previous Brazilian studies have indicated that working in agriculture
      could lead to an increased riskof penile cancer. The present descriptive study
      aimed at establishing a possible association between penile cancer
      andagricultural occupation. Materials and methods: Data on a total of 103 penile
      cancer patients were obtained frommedical records of two reference centres for
      cancer treatment in the state of Paraiba, Northeast Brazil. Informationabout
      sexual behaviour was obtained in interviews for 48 cases. Results: Of 103
      patients 38 and 52 were illiterateand had not completed graduation, respectively,
      and 60 earned less than twice the minimum wage. All together, 72(70%) worked in
      agriculture and 39 confirmed involvement in application of agrochemicals. A
      history of phimosiswas noted for 42 (69%) out of 61 patients and 40 (59%) out of
      68 ever smoked. Pathological signs of HPV infectionwere detected in 45 (70%) out
      of 64 patients. Of the 48 interviewed patients, 27 (56%) confirmed sexual contact
      withprostitutes and eight (19%) out of 43 had sex with animals. Conclusions: Data
      confirmed the presence of several riskfactors for penile cancer, like phimosis,
      smoking, HPV infection and promiscuous sexual behaviour. The high numberof
      Brazilian agricultural workers with penile cancer was unexpected if compared with
      other professional groups. Futurestudies should focus on this group of men and
      elucidate possible reasons for their increased risk.

PMID- 29374408
TI  - Cancer Diagnosis Epigenomics Scientific Workflow Scheduling in the Cloud
      Computing Environment Using an Improved PSO Algorithm
AB  - Objective: Epigenetic modifications involving DNA methylation and histone statud
      are responsible for the stablemaintenance of cellular phenotypes. Abnormalities
      may be causally involved in cancer development and thereforecould have diagnostic
      potential. The field of epigenomics refers to all epigenetic modifications
      implicated in controlof gene expression, with a focus on better understanding of
      human biology in both normal and pathological states.Epigenomics scientific
      workflow is essentially a data processing pipeline to automate the execution of
      various genomesequencing operations or tasks. Cloud platform is a popular
      computing platform for deploying large scale epigenomicsscientific workflow. Its
      dynamic environment provides various resources to scientific users on a pay-per
      use billingmodel. Scheduling epigenomics scientific workflow tasks is a
      complicated problem in cloud platform. We here focusedon application of an
      improved particle swam optimization (IPSO) algorithm for this purpose. Methods:
      The IPSOalgorithm was applied to find suitable resources and allocate epigenomics
      tasks so that the total cost was minimizedfor detection of epigenetic
      abnormalities of potential application for cancer diagnosis. Result: The results
      showed thatIPSO based task to resource mapping reduced total cost by 6.83 percent
      as compared to the traditional PSO algorithm.Conclusion: The results for various
      cancer diagnosis tasks showed that IPSO based task to resource mapping canachieve
      better costs when compared to PSO based mapping for epigenomics scientific
      application workflow.

PMID- 29374409
TI  - Synthesis, Characterization, and Evaluation of Cancer Prevention Activity of
      Novel Modified Heterocyclic Compounds
AB  - Anticancer approaches may employ change of molecular structure to enhance
      preventive influence of chemicalagents. The present examination concerned the
      potential anticancer impact of modified heterocyclic compounds. Astrategy was
      developed to combine tetrazole moieties from different diamines with 2
      aminobenzoic and substitutedbenzoyl chloride compounds with attention to
      synthesis, characterization and assessment of cancer preventive activity,applying
      IR, 1HNMR, 13CNMR and Mass spectra.

PMID- 29374410
TI  - Dose Calculation Accuracy of AAA and AcurosXB Algorithms for Small Central and
      Interface Lung Lesions - Verification with Gafchromic Film Dosimetry
AB  - Dose calculation for small field radiotherapy with heterogeneity often involves
      discrepancies, so that algorithmsused by treatment planning systems (TPS) should
      be evaluated with reference to achieving optimal treatment results.Accuracy of
      two model based algorithms, AcurosXB (AcXB) and the analytical anisotropic
      algorithm (AAA) fromEclipse TPS, were here tested. Measurements are made using
      Gafchromic EBT3 films with indigenously generated lungphantoms irradiated with 6
      MV photons. Lung phantoms contained two types of tumor plugs, one kept at an
      interfaceattached to the chest wall in right lung (RIT) and the other at the
      centre of the left lung (LCT). RIT and LCT werestudied with two different tumor
      diameters, 1.5 cm and 2.5 cm. Scanned images were planned in TPS with 3D-CRT,IMRT
      and VMAT and individual plans for each tumor were irradiated keeping the
      Gafchromic film at the centre ofthe tumor to evaluate the dose distribution in
      the central plane. Both algorithms, irrespective of delivery techniques,showed
      more deviation with smaller than larger diameter tumors. Also, both demonstrated
      maximum deviation at thejunction of tumor and lung in both RIT and LCT cases.
      However, the deviation observed was higher with AAA and aminimal acceptable
      deviation of within 4 % was achieved with AcurosXB.

PMID- 29374411
TI  - Fast Foods, Sweets and Beverage Consumption and Risk of Colorectal Cancer: A Case
      Control Study in Jordan
AB  - Background: The effects of consuming fast foods, sweets and beverages on the
      development of colorectal cancer(CRC) are unclear. The aim of this case-control
      study was to assess possible associations between the consumptionof different
      fast foods, sweets and beverages and CRC risk in a Jordanian population. Methods:
      Two hundred andtwenty diagnosed CRC cases and 281 controls were enrolled. Diet
      history was obtained using a validated quantitativequestionnaire. Results:
      Consumption of some types of fast food, and particularly falafel, was associated
      with an increasedrisk of developing CRC. Elevated risk was found for potato and
      corn chips with an AOR of 4.36 (95%CI: 1.24-15.28)for daily consumption and 3.33
      (95%CI: 1.00-11.11) for >=5 servings/week. Consuming 1-2 or >5 servings per week
      offried potatoes or 2-3 servings per week of chicken in sandwiches also increased
      the risk while exposure to fresh tomatojuice and hot pepper sauce on a monthly
      basis appeared to exert a protective effect. Conclusions: Consumption of
      friedfast food items was significantly linked with an increased risk of
      developing CRC in Jordan.

PMID- 29374412
TI  - Lack of Association between Red Meat Consumption and a Positive Fecal
      Immunochemical Colorectal Cancer Screening Test in Khon Kaen, Thailand: a
      Population- Based Randomized Controlled Trial
AB  - Background: There is convincing evidence from epidemiological studies that meat
      consumption increasescolorectal cancer (CRC) risk. However, assessment of any
      association with a positive fecal immunochemical test(FIT) in CRC screening has
      been limited. If a link could be shown this might be helpful for establishing a
      risk groupfor colonoscopy. Objective: This study aimed to assess any association
      between meat consumption and other lifestylefactors and a positive FIT result in
      a Thai population. Methods: A cross-sectional analytical study was conducted
      with1,167 participants in a population-based randomized controlled trial. CRC was
      screened from May 2016 - February2017. Subjects aged 45-74 years who met the
      eligibility criteria were randomly allocated to the study arm. A positiveFIT was
      determined with cut-off 100 ng/mL. Multiple logistic regression was used to
      analyze any relationship betweenlifestyle factors and a positive FIT. Result: The
      total number of subjects was 1,060 (90.8% return rate of FIT). WithFIT100,
      FIT150, and FIT200, positive tests were found in 92 (8.68%), 74 (6.98%), and 60
      (5.66%), respectively. Nosignificant associations were noted with any of the
      variables, except for being aged 60-74 years (ORadj = 1.62, 95%CI: 1.03-2.54)
      Borderline significance was observed for high consumption of vegetables (ORadj =
      0.62, 95% CI:0.36-1.07) and being male (ORadj = 1.39, 95% CI: 0.87-2.22).
      Conclusion: Despite the evidence from the literature,no association was here
      found between a positive FIT result and meat consumption or other well
      established lifestyleparameters. Being aged 60-74 years was a risk factor which
      should be taken into account in CRC screening strategyin countries like Thailand
      with limited access to endoscopy.

PMID- 29374413
TI  - Photodynamic Cancer Therapy Using Wavelet Based Monte Carlo Computation of Light
      Absorption with a Genetic Algorithm
AB  - Objective: The method to treating cancer that combines light and light-sensitive
      drugs to selectively destroytumour cells without harming healthy tissue is called
      photodynamic therapy (PDT). It requires accurate data for lightdose distribution,
      generated with scalable algorithms. One of the benchmark approaches involves
      Monte Carlo (MC)simulations. This gives an accurate assessment of light dose
      distribution, but is very demanding in computation time,which prevents routine
      application for treatment planning. Methods: In order to resolve this problem, a
      design forMC simulation based on the gold standard software in biophotonics was
      implemented with a large modern waveletbased genetic algorithm search (WGAS).
      Result: The accuracy of the proposed method was compared to that with thestandard
      optimization method using a realistic skin model. The maximum stop band
      attenuation of the designed LP,HP, BP and BS filters was assessed using the
      proposed WGAS algorithm as well as with other methods. Conclusion:In this paper,
      the proposed methodology employs intermediate wavelets which improve the
      diversification rate of thecharged genetic algorithm search and that leads to
      significant improvement in design effort efficiency.

PMID- 29374414
TI  - A Modified Epirubicin and Oxaliplatin Plus Capecitabine (EOX) Regimen as a Second
      Line Therapy in Patients with Advanced Gastric Cancer
AB  - Objective: We aimed to evaluate the effectiveness of an mEOX (modified
      epirubicin, oxaliplatin plus capecitabine)regimen as second line therapy after
      failure of mDCF (modified docetaxel, cisplatin plus fluorouracil). Methods:
      Gasticcancer patients for whom first-line therapy was unsuccessful and who
      subsequently received mEOX (epirubicin 50 mg/m2 on day 1, oxaliplatin 85 mg/m2
      day 1 and capecitabine twice-daily dose of 625 mg/ m2, p.o. for 2 weeks) every
      3weeks until disease progression or unacceptable toxicity, were retrospectively
      analyzed. Results: The study populationcomprised 129 cases with a median age of
      55 years (range= 27-78), the majority being male (76 %). Most (75.2%)had >= 2
      sites of metastasis. The median number of chemotherapy courses was five (range= 2
      9). Forty-nine achieveda partial response and 33 showed stable disease, resulting
      in a ORR (overall response rate) of 38% and a DCR (diseasecontrol rate) of 63.6%.
      The most frequent features of grade 3-4 hematological and non-hematological
      toxicity wereneutropenia (8.5%) and nausea/vomiting (5.4%). None of the patients
      suffered death due to toxicity. The median PFSwas 4.7 months (95% CI, 4.1-5.3)
      and the OS was 7.4 months (95% CI, 6.3-8.5). On multivariate analysis, age >=
      60years and ECOG performance status (0-1) were independent prognostic factors
      affecting PFS and OS. Conslusions:In advanced gastric cancer patients, who
      progress after first line chemotherapy and have an ECOG performance statusof 0-1,
      mEOX is a well tolerated triple regimen associated with a promising OS and PFS.

PMID- 29374415
TI  - [Inhibitors of cyclin-dependent kinases (CDK) - a new group of medicines in
      therapy of advanced breast cancer].
AB  - Cyclin-dependent kinases (CDKs) are a family of enzyme proteins present in cell
      nuclei that regulate the various stages of the cell cycle. They act as proto
      oncogens, and increased expression of some of these proteins (CDK4 and CDK6) is
      observed in breast cancer cells and associated with decreased sensitivity to anti
      estrogen therapy. CDK inhibitors are chemicals that inhibit the enzymatic
      activity of specific CDKs. Currently three drugs in this group are available on
      the market and are registered for the treatment of advanced HR-positive, HER2
      negative breast cancer. Two drugs in this class (palbociclib and ribociclib) are
      registered for first-line treatment in combination with letrozole, two
      (palbociclib and abemaciclib) are approved for second line therapy in combination
      with fulvestrant. In both indications, the addition of a CDK inhibitor to
      standard hormone therapy doubled the median progression-free survival (PFS).

PMID- 29374416
TI  - [Type and frequency of cardiac symptoms in patients with pulmonary sarcoidosis].
AB  - AIM: The aim of the study was to assess the type and frequency of prevalence of
      cardiac symptoms in patients with pulmonary sarcoidosis. MATERIALS AND METHODS:
      The study group consisted of 54 patients (21 female, 33 male), with biopsy-proven
      pulmonary sarcoidosis. Mean age was 45.85 +/-11.77 years. According to time
      passed from diagnosis of sarcoidosis patients were divided into 2 subgroups.
      Additionally, age, sex, left ventricular ejection fraction, cigarette smoking and
      comorbidities were analyzed. Course and stage of sarcoidosis were also included
      in the analysis. RESULTS: The frequency of cardiovascular symptoms in the study
      group was 87.04%. 59.26% of patients reported chest pain, the same subjects
      reported dyspnoea. 48.15% of respondents reported heart palpitations, 33.33% pre
      syncope states, 12.96% syncope, and 37.04% edema of lower limbs. There were no
      statistically significant differences in the incidence of analyzed symptoms,
      depending on the duration of lung sarcoidosis. CONCLUSIONS: Patients with
      pulmonary sarcoidosis who report cardiovascular symptoms require further
      diagnostics.

PMID- 29374417
TI  - [Thyroid dysfunction in patients with small intestinal bacterial overgrowth].
AB  - : Small intestinal bacterial overgrowth (SIBO), similarly as thyroid diseases, is
      characterized by chronic diarrhea or constipation, but it is not known whether
      there is a causal relationship between these disorders. AIM: The aim of the study
      was to assess thyroid function indices in different clinical forms of SIBO.
      MATERIALS AND METHODS: The study was performed in 34 patients with diarrhea
      predominant SIBO (group I), 30 with constipation predominant SIBO (group II) and
      30 clinically healthy subjects (control group - K). Small intestinal bacterial
      overgrowth was assessed with lactulose hydrogen breath test (LHBT) using the
      breath-hydrogen analyzer (Gastrolyser, Bedfont). Serum thyrotropin (TSH), free
      triiodothyronine (FT3) and free thyroxine (FT4) levels were determined by
      immunochemical method (ELFA) and anti-thyroid peroxidase (ATPO) protein level by
      immunoenzymatic method (ELISA). RESULTS: LHBT value was respectively in groups: K
      - 8,5 +/- 2,9 ppm, I - 66,9 +/- 16,9 ppm, II- 62,0 +/- 15,5 ppm (p <0,001). The
      levels of hormones were similar in group K and I, whereas in group II
      differentiated: FSH 2,5 +/- 0,7 vs. 3,8 +/- 1,8 mU/L (p <0,05), FT3- 5,1 +/- 1,2
      vs. 3,7 +/- 1,0 mU/L (p <0,05), FT4 - 14,1 +/- 2,5 vs. 9,4 mU/L (p <0,01). In
      both groups of patients the levels of ATPO were statistically significantly
      higher than in the control group - respectively: K - 6,3 +/- 3,1 IU/ml , I - 39,9
      +/- 23,4 IU/ml (p < 0,001), II - 94,1 +/- 56,3 IU/ml (p <0,001). CONCLUSIONS:
      Thyroid function may be impaired in patients with small intestinal bacterial
      overgrowth which should be taken into account in the diagnostic and therapeutic
      management of the diseases of these organs.

PMID- 29374418
TI  - Fast apixaban-related resolution of left ventricular thrombi in a patient with
      dilated cardiomyopathy.
AB  - Left ventricular thrombi (LVTs) develop most often in patients with post
      myocardial left ventricular dysfunction and in cardiomyopathies, particularly in
      dilated cardiomyopathy (DCM). They constitute a danger of systemic embolization.
      So far, direct-acting oral anticoagulants (DOACs), including apixaban - a
      selective inhibitor of active Factor X, have not been systematically investigated
      in patients with LVTs; study comparing the efficacy of apixaban and warfarin has
      been undertaken only recently. A few case reports or case series presenting
      patients with LVTs treated with DOACs are available in the literature. The
      authors described a case of a 53-year-old male with DCM, hospitalized due to
      heart failure exacerbation. In echocardiography, apart from typical features of
      DCM, three apical LVTs connected with false tendons were revealed. Treatment with
      apixaban was introduced, initially in a dose of 2.5 mg twice daily, as creatinine
      concentration was 2.0 mg/dl, and after 2 days - when creatinine concentration
      dropped, the dose was augmented to 5 mg twice a day. Gradual resolution of LVTs
      was observed from day 3; they disappeared completely after one week. There were
      no symptoms of systemic embolization. The patient was discharged with advice to
      take apixaban permanently. To the best of the authors knowledge, the case
      presented is the fastest resolution of LVTs during therapy with apixaban reported
      in the literature and the first description of DOAC use for multiple LVTs.

PMID- 29374419
TI  - Implantable cardioverter defibrillator does not cure the heart.
AB  - A man with non-ischemic cardiomyopathy, EF 22%, permanent AF and ICD was admitted
      for elective device replacement. The need for the optimization of the ventricular
      rate and avoidance of right ventricular pacing made it necessary to up-grade the
      existing pacing system using direct His bundle pacing and dual chamber ICD. This
      enabled the regularization of ventricular rate, avoiding the RV pacing and
      optimize the beta-blocker dose. The one month follow-up already showed reduction
      in left ventricle diameter, improvement in ejection fraction, NYHA class decrease
      to II. The His bundle pacing enabled the optimal treatment of the patient
      resulting in excellent clinical improvement.

PMID- 29374420
TI  - [The impact of electronic cigarettes usage on the endothelial function and the
      progression of atherosclerosis].
AB  - The exponetial growth in popularity of electronic cigarettes in the world markets
      intensifies the debate about their health effects. The smoking of traditional
      tabacoo products is a factor associated with the endothelium damage and
      progression of atherosclerosis. The elimination of the combustion process in
      electronic cigarettes allows to conclude that they are less harmful to a vascular
      endothelium than traditional tobacco products. E-cigarette aerosol contains many
      compounds that have an influence on initiation and progression of
      atherosclerosis. Nicotine protherogenic action is not fully explained. On one
      hand, nicotine modifies metabolic pathways leading to atherosclerosis, whereas
      epidemiological studies do not show an increased risk of cardiovascular disease
      in the population using nicotine replacement therapy or snuff. Acrolein,
      formaldehyde and the ultrafine particles generated during e-liquid heating have
      an impact on initiation and progression of atherosclerosis, but their level is
      lower than that of tobacco smoke. In order to assess accurately the longterm
      effects of e-cigarettes, it is necessary to conduct epidemiological studies
      measuring the effects of using e-cigarettes. It is claimed that the use of
      electronic cigarettes has a potential impact on the development of
      atherosclerosis, but is significantly lower than that of traditional cigarettes.

PMID- 29374421
TI  - [Celiac disease - disease of children and adults: symptoms, disease
      complications, risk groups and comorbidities].
AB  - About 1% of human population suffers from celiac disease (CD) and it is one of
      the most commonly diagnosed autoimmune disorders. Until recently it was believed
      that CD affects mainly children, but as the newest studies show, up to 60%
      recently diagnosed patients are adults, often over the age of 60. CD's medical
      signs are nonspecific. Atypical course of the disease with extraintestinal
      symptoms is being increasingly observed. The disease may also be asymptomatic
      over many years. The studies show that the average diagnosis of CD takes more
      than 10 years since the first symptoms appear. Nonspecific medical signs cause
      undiagnosed patients suffering from CD to visit gastroenterologists,
      endocrinologists, allergists, gynaecologists and other medical specialists.
      However, most frequently general practitioners have the first encounter with
      patients suffering from CD, therefore they are able to recognize symptoms of the
      disease at the earliest and refer the patient to a gastroenterologist. Early
      diagnosis and beginning of the treatment reduce complications of untreated CD.
      The aim of this paper is to show general practitioners symptoms, disease
      complications, risk groups and comorbidities of CD.

PMID- 29374422
TI  - [Fixed and temporary keratoprosthesis].
AB  - Keratoprosthesis is a chance for all patients who have bilateral visual loss due
      to corneal pathology so serious and extensive that it cannot be removed by graft
      transplantation. This problem mainly affects less developed countries. The
      eyesight of these patients could return to normal if corneal transplants were
      practiced and keratoprosthesis were widely available. Keratoplasty makes great
      progress and gets better and better results. The future will show whether there
      will be more reliable and biologically integrated keratoprosthesis, with low risk
      of complications.

PMID- 29374423
TI  - Un siglo del Instituto Nacional de Salud y una proyeccion para los proximos anos.

PMID- 29374424
TI  - On the tenth value distance of the photon field along the maze of high-energy
      linear accelerator vaults.
AB  - There is a wide range in the reported photon tenth value distance (TVD) in the
      maze of high-energy linear accelerator vaults. In order to gain insight into the
      appropriate use of the TVD value during door design, we performed measurements of
      the photon dose in the maze of four vaults. In addition, our study represents the
      first to describe a scenario where an inner borated polyethylene (BPE) door for
      neutron shielding is installed in the maze downstream to Point A, the point on
      the maze centerline that is just visible from the isocenter. The measurements
      were made along the maze centerline at 1 m above the floor. In all cases, the
      accelerator operated at a nominal energy of 15 MV. Of the four vaults, three were
      equipped with an inner BPE door at a distance of 1.0-2.1 m downstream to Point A.
      The door was made of 10.16 cm (4") BPE sandwiched between two 0.635 cm (1/4")
      steel face plates. The photon dose in the maze without a BPE door decreases
      exponentially with a characteristic TVD of 6 m beyond a distance of 2.5 m from
      Point A. The presence of a BPE door in an identical vault not only reduces the
      photon intensity in the maze by about an order of magnitude, but also softens the
      energy spectrum with a shortened TVD of 4.7 m, significantly lessening the
      shielding burden at the outer maze entrance. In contrast to the common use of
      Point A as the reference point to specify distance, the photon dose in the maze
      with a BPE door located downstream to Point A can be satisfactorily described as
      exponential functions of the distance measured from the door, which shows good
      consistency among the three vaults of different room parameters.

PMID- 29374425
TI  - Complement system in lung transplantation.
AB  - The complement system is a cascade of multiple proteins that have been known to
      mediate inflammatory response. This tightly regulated system has been recognized
      to play a role in adaptive immunity via humoral and cell-mediated processes.
      There is evidence from animal and human studies that the complement system is
      involved in various outcomes of solid organ transplantation. Most of the studies
      have been done in the field of kidney transplantation. In this paper, we review
      the studies looking at lung transplantation. The complement cascade appears to
      have a prominent role in mediating lung allograft damage in the setting of
      ischemia-reperfusion injury, humoral rejection, as well as chronic allograft
      dysfunction. In this review, we look at the available data regarding the role of
      complement in these outcomes and propose some ideas about future direction of
      research in this field.

PMID- 29374426
TI  - [Quorum sensing in Gram-negative bacteria: signal molecules, inhibitors and their
      potential therapeutic application].
AB  - Quorum Sensing (QS) is a phenomenon of chemical cell-to-cell communication
      consisting in the synthesis and secretion of signal molecules called autoinducers
      into the environment, which contribute in regulation of various physiological
      processes. QS was identified in different bacterial species, including symbiotic
      and pathogenic bacteria. QS systems play a crucial role in regulation of
      expression of genes which control motility, biofilm formation, and synthesis of
      virulence factors by pathogenic bacteria. These systems recognize signal
      molecules of different specificity which belong to a few groups and enable intra-
      and interspecific communication of bacterial cells as well as communication with
      cells of eukaryotic organisms (hosts). Inhibition of QS called Quorum Quenching
      (QQ) is now regarded to be a promising strategy to combat bacterial infections.
      So far, a large group of substances of natural and synthetic origin with a
      function of QS inhibitors, which can have potential therapeutic applications, has
      been identified.

PMID- 29374427
TI  - [Inhibitors of enzymes with potential medical applications].
AB  - From the earliest times, medicine has focused on finding the most suitable and
      effective treatment for every patient. At present, a dynamic development of
      diagnostic methods and techniques for designing new drugs allows to create
      therapies for many diseases at the molecular level. Among the many drugs
      appearing on the medical market every year, special attention should be paid to
      those whose action is based on the inhibition of proteolytic enzyme activity.
      Protease inhibitors are a diverse group of biologically active molecules for
      which antiviral, antimicrobial, antifungal, antiparasitic or anticancer effects
      have been documented. Successes in the treatment of HIV infection, hepatitis C
      and influenza diseases certainly encourage researchers to look for new inhibitors
      that could be used in new therapies. This paper provides an overview of selected
      information on enzyme inhibitors, especially protease inhibitors, which are
      already registered medicines and substances that are promising candidates for
      medical use.

PMID- 29374428
TI  - [Metalloproteases and their inhibitors: role in pathogenesis of selected
      examples].
AB  - Proteolytic enzymes and their inhibitors are crucial in host-pathogen
      interaction. Metalloproteases secreted by pathogenic microbes play an important
      role in destroying not only host tissues but also their immune proteins.
      Metalloproteinase inhibitors, in contrast, may serve as effective therapeutic
      agents, which is especially important because of the increasing number of
      microorganisms resistant to known antibiotics. The role of metalloproteases
      produced by the bacterium Pseudomonas aeruginosa in the colonization of the host
      organism is described. Attention has also been paid to the role of inhibitors of
      these enzymes in defense responses and underlined their potential role in
      inhibiting the development of infection.

PMID- 29374429
TI  - [The involvement of matrix metalloproteinases in the development and progression
      of neoplasm diseases].
AB  - Neoplasm diseases are one of the main causes of death in Poland and worldwide.
      Forming and progression of tumour are regulated by the number of factors, among
      which one of the most important are matrix metalloproteinases (MMPs), zinc
      dependant proteases, responsible for remodeling of extracellular matrix (ECM).
      They may induce cancer progression directly by modifying the ECM, enabling cancer
      growth and migrating of cells released from tumour, as well as invading adjacent
      tissue and blood or lymphatic vessels. MMPs may also induce carcinogenesis in
      indirect way by modifying tumour microenvironment and secreting factors promoting
      or inhibiting particular processes. There is number of factors secreted by cancer
      cells, stromal components and ECM elements regulating activation and
      functionality of matrix metalloproteinases. Understanding the mechanisms and
      pathways underlying regulation and activation of MMPs is crucial for
      comprehension of carcinogenesis and metastasis, and may contribute to developing
      of new therapeutic strategies.

PMID- 29374430
TI  - [Ubiquitin-proteasome pathway as a target for therapeutic strategies].
AB  - In Eukaryota, the majority of intracellular proteins are degraded by the
      ubiquitin-26S proteasome pathway. Through degradation of proteins tagged with
      polyubiquitin chains, the 26S proteasomes, multicatalytic proteolytic complexes,
      participate in regulation of key cellular processes such as cell cycle,
      proliferation and cell differentiation, apoptosis, transcription, signal
      transduction, morphogenesis, immune response, response to stress and to
      extracellular effectors, modulation of cell-surface receptors, antigen
      presentation, proteolysis of enzymes and regulatory proteins, and protein quality
      control in endoplasmic reticulum. Dysfunction of the ubiquitin-proteasome pathway
      is associated with many diseases, including cancer, neurodegeneration, autoimmune
      and inflammatory response, as well as infectious diseases. In recent years,
      besides proteasomes, the enzymes that drive ubiquitination and deubiquitination
      have entered clinical trials as potential therapeutic targets. Small molecular
      inhibitors against proteasomes have been discovered, as well as inhibitors of the
      ubiquitin cascade enzymes and deubiquitinating enzymes. Second generation
      inhibitors of proteasomes have been successfully approved for clinical
      application.

PMID- 29374431
TI  - [Biologically active compounds and methods of their removal through
      biocatalysis].
AB  - Pharmaceuticals and other biologically active substances are produced in
      increasing numbers. Because of increased usage and improper storage, they pass
      into surface water, ground water and drinking water directly or through
      wastewaters. This is a threat to many living organisms, including humans, because
      of hormonal imbalances primarily related to reproductive processes or the problem
      of microbial drug resistance. Due to the scale of the emission and limited
      possibilities of decomposition of these pollutants by physico-chemical methods it
      is necessary to develop new efficient processes. One of the proposed solutions is
      the use of tools offered by biocatalysis. Thanks to the biocatalysis process, a
      wide range of biologically active compounds can be removed, by using of enzymes
      with low substrate specificity and operating in environmentally friendly
      conditions. Recent studies indicate the effectiveness of those methods used in
      the removal of pollutants of different chemical structure, with the formation of
      non-toxic metabolites.

PMID- 29374432
TI  - [Different faces of phenoloxidase in animals].
AB  - Phenoloxidases are oxidoreducting enzymes whose main function is the oxidation of
      phenols. The term phenoloxidase is often used interchangeably to describe three
      different enzymes: tyrosinase (EC 1.14.18.1), catechol oxidase, and laccase. Of
      these, only tyrosinase has two activities: (1) oxygenase activity to hydroxylate
      monophenols to ortho-diphenols and (2) oxidase activity responsible for further
      oxidation of ortho-diphenols to ortho-quinones. Tyrosinase is a key enzyme
      involved in the melanogenesis process, resulting in the formation of black-brown
      eumelanin and yellow-red feomelanin. In addition to the pigmentary role, human
      melanin protects against harmful ultraviolet radiation, while in invertebrate
      animals melanin is involved in the process of cuticle hardening, wound healing,
      clot formation, maintenance of intestinal homeostasis and defense reactions. In
      invertebrates, the tyrosinase is synthesized as a proenzyme that is activated by
      a serine proteases' cascade known as the phenoloxidase system. This system is
      considered as one of the innate immunity mechanisms.

PMID- 29374433
TI  - [Biological significance of edible mushrooms in mycoremediation].
AB  - The importance of fungi in environmental remediation is due both to their ability
      to biotransformation of xenobiotics and to accumulate heavy metals. These
      processes depend primarily on the species, while the role of the species or
      systematic affiliation is less important, as is the strategy of symbiosis, for
      example: mycorrhiza, parasitism or saprophytism. The main factors controlling the
      absorption of metals by mushrooms are bioavailability and soil type, while
      xenobiotics are dependent on soil factors such as cation exchange capacity, pH,
      or organic matter content. The composition of the substrate is an important
      factor as there are large differences in the intake of individual substances. The
      composition, the amount of impurities present, but also the age of the mycelium
      that may be present in nature for many years or (compared) only for several
      months under culture conditions. It is a well-known fact that the content of
      mushroom fruiting bodies is correlated with the emission of pollutants.

PMID- 29374434
TI  - [Industrial application of lipases].
AB  - The ability of lipases to perform specific reactions of transformation
      (biotransformation) makes these enzymes a useful tool used in many syntheses, for
      example: in the production of detergents, cosmetics, biosurfactants, in the oil
      chemical, paper, dairy, food or pharmaceutical industries. Lipases are ubiquitous
      enzymes but only lipases produced by microorganisms are important for industrial
      applications due to their wide variety of properties such as stability in organic
      solvents, action under mild conditions, high substrate specificity and region-
      and enantioselectivity, as well as the relatively simple methods of their
      production in fermentors and recovery from the culture medium. This paper reviews
      the latest achievements in the production of lipases in the submerged
      fermentation and solid state fermentation using waste products from the
      agricultural industry. In addition, new applications of lipases were described,
      including those for the synthesis of biopolymers and biodiesel and for the
      production of enantiomeric pharmaceuticals, agrochemicals and flavoring
      compounds.

PMID- 29374436
TI  - Rebooting the generally recognized as safe (GRAS) approach for food additive
      safety in the US.
AB  - The US Food and Drug Administration (FDA) has premarket review authority over
      food additives, but a food manufacturer may, according to the legislation,
      intentionally add a substance to human food or animal food without their
      premarket review or approval if the substance is generally recognized, among
      qualified experts, to be safe under the conditions of its intended use. Generally
      recognized as safe (GRAS) implies that the current scientific community agrees on
      the adequacy of how data is generated. This system has come under public pressure
      because of doubts as to its efficiency and the FDA's recent GRAS rule is part of
      the response. The FDA guidance for testing food additives, known as the
      "Redbook", is about two decades old. Work toward a new "Redbook" is on the way,
      but the US Grocery Manufacturer Association (GMA) also has initiated the
      development of an independent standard on how to perform GRAS determinations.
      This review of the current guidance shows a very rigorous system for higher
      concern levels, but also many waiving options. Opportunities and challenges for
      safety evaluations of food additives are discussed. Where scientific progress has
      allowed improving existing and adapting new methods, these should be adopted to
      improve product safety and animal welfare. The continuous adaptation of such
      improved methods is therefore needed. Especially, there are opportunities to
      embrace developments within the toxicity testing for the 21st century movement
      and evidence-based toxicology approaches. Also, the growing understanding of the
      limitations of traditional tests needs to be considered.

PMID- 29374435
TI  - A Human Chondrocyte-Derived In Vitro Model of Alcohol-Induced and Steroid-Induced
      Femoral Head Necrosis.
AB  - BACKGROUND Worldwide, femoral head necrosis (FHN), which is also known as
      avascular necrosis of the femoral head or osteonecrosis of the femoral head,
      affects millions of people. Excess alcohol intake and steroid use are two common
      associations with FHN, but their pathogenesis remains unknown. The aim of this
      study was to develop an in vitro model using human chondrocytes to study alcohol
      induced and steroid-induced FHN. MATERIAL AND METHODS In this study, the in vitro
      model used a monolayer culture of articular chondrocytes derived from patients
      with non-traumatic FHN (Ficat and Arlet, Stage III). Normal chondrocytes were
      obtained from patients with femoral neck fracture resulting from road traffic
      accident (Garden, Stage IV). Alcohol-stimulated and steroid-stimulated articular
      chondrocytes were evaluated by a cell proliferation assay, measurement of calcium
      levels (alizarin red), measurement of alkaline phosphatase (ALP) levels,
      detection of glycosaminoglycan (GAG) secretion using safranin O histochemical
      staining, and analysis of cartilage-specific genes, ACAN, SOX9, OPG, TGF-beta,
      RANKL, and RUNX2, using quantitative real-time polymerase chain reaction (qRT
      PCR). RESULTS Both alcohol and steroids, but especially steroids, accelerated the
      degradation of cartilage by suppression of chondrogenesis while promoting
      chondrocyte hypertrophy and activating osteogenic differentiation, as assessed by
      cell proliferation assay, detection of glycosaminoglycan (GAG) secretion, and
      analysis of cartilage-specific genes. CONCLUSIONS A human chondrocyte-derived in
      vitro model of alcohol-induced and steroid-induced FHN demonstrated chondrocyte
      hypertrophy and activated osteogenic differentiation.

PMID- 29374437
TI  - Comment on "Alternative acute oral toxicity assessment under REACH based on sub
      acute toxicity values".

PMID- 29374438
TI  - Reply to Comment on "Alternative acute oral toxicity assessment under REACH based
      on sub-acute toxicity values".

PMID- 29374439
TI  - 1st INEXO Symposium: Alternative models in vitro, ex ovo and organisms: From
      research to applications in pathologies and aging.

PMID- 29374440
TI  - In silico methods - Computational alternatives to animal testing.

PMID- 29374441
TI  - A New Burgess Shale Polychaete and the Origin of the Annelid Head Revisited.
AB  - Annelida is one of the most speciose (~17,000 species) and ecologically
      successful phyla. Key to this success is their flexible body plan with metameric
      trunk segments and bipartite heads consisting of a prostomium bearing sensory
      structures and a peristomium containing the mouth. The flexibility of this body
      plan has traditionally proven problematic for reconstructing the evolutionary
      relationships within the Annelida. Although recent phylogenies have focused on
      resolving the interrelationships of the crown group [1-3], many questions remain
      regarding the early evolution of the annelid body plan itself, including the
      origin of the head [4]. Here we describe an abundant and exceptionally well
      preserved polychaete with traces of putative neural and vascular tissues for the
      first time in a fossilized annelid. Up to three centimeters in length,
      Kootenayscolex barbarensis gen. et sp. nov. is described based on more than 500
      specimens from Marble Canyon [5] and several specimens from the original Burgess
      Shale site (both in British Columbia, Canada). K. barbarensis possesses biramous
      parapodia along the trunk, bearing similar elongate and thin notochaetae and
      neurochaetae. A pair of large palps and one median antenna project from the
      anteriormost dorsal margin of the prostomium. The mouth-bearing peristomium bears
      neuropodial chaetae, a condition that is also inferred in Canadia and
      Burgessochaeta from the Burgess Shale, suggesting a chaetigorous origin for the
      peristomial portion of the head and a secondary loss of peristomial parapodia and
      chaetae in modern polychaetes.

PMID- 29374442
TI  - Coconut crabs.
AB  - Mark Laidre introduces the coconut crab (Birgus latro), the world's largest
      terrestrial invertebrate.

PMID- 29374443
TI  - Cavefishes.
AB  - Life in caves means life in perpetual darkness. This has two dramatic effects on
      animals: it eliminates the need to see and reduces the availability of food as
      there is no local photosynthesis. Food availability for cave dwellers is often
      seasonal, episodic or unscheduled. Like other cave animals, fish species adapted
      for cave life exhibit a suite of sensory, morphological, physiological and
      behavioral traits that are shared among species from phylogenetically distant
      families. Most cave fishes are entirely or partially blind. The most extreme of
      them, the obligatory cave-dwelling fish that spend their entire life in caves,
      are the subject of this primer. At present, over 200 such cavefish species have
      been described, and all of them have evolved independently from surface
      ancestors. Thus, each cavefish species is a replicate of the same natural
      experiment, testing the evolutionary response of a sighted surface fish to the
      absence of light and the limitations on food in a subterranean environment. The
      evolutionary responses converge on loss of eyes and pigmentation and the
      augmentation of other senses, such as taste, smell or mechanosensation, as well
      as a more efficient metabolism, changes in feeding behavior, altered activity
      levels, loss of circadian rhythmicity and increased wakefulness. However, not all
      of these troglomorphic traits are present in every cavefish species.

PMID- 29374444
TI  - Wild Sri Lankan elephants retreat from the sound of disturbed Asian honey bees.
AB  - Asian elephants (Elephas maximus) are threatened primarily by habitat loss and
      human-elephant conflict. In addition to establishing protected areas and
      corridors for wildlife, empowering farmers to protect their crops is crucial for
      Asian elephant conservation [1,2]. Elephants can habituate to artificial
      deterrents, hence natural biological alternatives are of great interest [2,3].
      African elephants (Loxodonta africana) avoid African honey bees (Apis mellifera
      scutellata), inspiring 'beehive fences' as a successful means of small-scale crop
      protection [4,5]. Here, we used a recording of a disturbed hive of cavity
      dwelling Asian honey bees (Apis cerana indica) and conducted sound playbacks to
      120 wild elephants in 28 different groups resting under trees in Uda Walawe
      National Park in Sri Lanka. Elephants responded by moving significantly further
      away from their resting site in bee playback trials compared to controls.
      Elephants also increased vocalization rates, as well as investigative and
      reassurance behaviours in response to bee sounds, but did not display dusting or
      headshaking behaviour.

PMID- 29374445
TI  - Mitophagy: Vps13D Couples Mitochondrial Fission and Autophagic Clearance.
AB  - Mitophagy maintains mitochondrial homeostasis and cell health. A new study
      demonstrates that the ubiquitin-binding protein Vps13D functions downstream of
      the fission factor Drp1 to control mitochondrial size and autophagic clearance in
      Drosophila midgut cells.

PMID- 29374446
TI  - Speech Comprehension: Stimulating Discussions at a Cocktail Party.
AB  - When humans listen to speech, ongoing cortical oscillations entrain to the
      acoustic signal. New research demonstrates that electrically stimulating the
      brain in time with speech rhythm can improve intelligibility for speech in noise.

PMID- 29374447
TI  - Brain Rhythms: Higher-Frequency Theta Oscillations Make Sense in Moving Humans.
AB  - The hippocampal theta rhythm is critical for learning and memory. New research
      demonstrates that theta oscillations in freely moving humans are similar in
      frequency and function to those observed in rodents and are modulated by movement
      speed and exploratory behavior.

PMID- 29374448
TI  - Organelles: The Emerging Signalling Chart of Mitochondrial Dynamics.
AB  - Many molecular and functional details of single events in mitochondrial dynamics
      have been reported, but little is known about their coordination. A recent study
      describes how cellular Ca2+ signals, via remodelling the actin cytoskeleton,
      synchronise the formation of endoplasmic reticulum-mitochondria contacts with
      inner and outer mitochondrial membrane fission.

PMID- 29374449
TI  - Evo-Devo: The Double Identity of Insect Wings.
AB  - Sometime in the Devonian, perhaps about 400 million years ago, insects became the
      first clade to conquer the sky. Recent evo-devo studies have begun to unravel the
      mysterious origin of the flight structure that made insects into extraordinary
      six-legged fliers.

PMID- 29374450
TI  - Chromosome Biology: The Sight of DNA, at Last!
AB  - Chromosomes are shaped by the combined function of the condensin and cohesin Smc
      kleisin complexes. After more than two decades of research in this field, a new
      study finally sheds light on how these machines might interact with their DNA
      substrates.

PMID- 29374451
TI  - Sex Determination: Sterility Genes out of Sequence.
AB  - The canonical model for the evolution of separate sexes in plants invokes
      sterility mutations at two linked loci. A new study claims to have found them in
      asparagus, but the order of their origin does not conform to expectation.

PMID- 29374452
TI  - Antigen Presentation: Visualizing the MHC Class I Peptide-Loading Bottleneck.
AB  - The peptide-loading complex is a bottleneck in antigen presentation by major
      histocompatibility complex (MHC) class I molecules. While the structures of its
      individual components were known, the recent report of the 7.2 A structure of the
      entire complex now fits them into their functional context, explaining this
      monumental step in antigen acquisition by MHC class I molecules.

PMID- 29374453
TI  - Topographic Maps: Motor Axons Wait Their Turn.
AB  - Topographic maps are a basic organizational feature of nervous systems, and their
      construction involves both spatial and temporal cues. A recent study reports a
      novel mechanism of topographic map formation which relies on the timing of axon
      initiation.

PMID- 29374454
TI  - Resistance to Plum Pox Virus (PPV) in apricot (Prunus armeniaca L.) is associated
      with down-regulation of two MATHd genes.
AB  - BACKGROUND: Plum pox virus (PPV), causing Sharka disease, is one of the main
      limiting factors for Prunus production worldwide. In apricot (Prunus armeniaca
      L.) the major PPV resistance locus (PPVres), comprising ~ 196 kb, has been mapped
      to the upper part of linkage group 1. Within the PPVres, 68 genomic variants
      linked in coupling to PPV resistance were identified within 23 predicted
      transcripts according to peach genome annotation. Taking into account the
      predicted functions inferred from sequence homology, some members of a cluster of
      meprin and TRAF-C homology domain (MATHd)-containing genes were pointed as PPV
      resistance candidate genes. RESULTS: Here, we have characterized the global
      apricot transcriptome response to PPV-D infection identifying six PPVres locus
      genes (ParP-1 to ParP-6) differentially expressed in resistant/susceptible
      cultivars. Two of them (ParP-3 and ParP-4), that encode MATHd proteins, appear
      clearly down-regulated in resistant cultivars, as confirmed by qRT-PCR.
      Concurrently, variant calling was performed using whole-genome sequencing data of
      24 apricot cultivars (10 PPV-resistant and 14 PPV-susceptible) and 2 wild
      relatives (PPV-susceptible). ParP-3 and ParP-4, named as Prunus armeniaca PPVres
      MATHd-containing genes (ParPMC), are the only 2 genes having allelic variants
      linked in coupling to PPV resistance. ParPMC1 has 1 nsSNP, while ParPMC2 has 15
      variants, including a 5-bp deletion within the second exon that produces a
      frameshift mutation. ParPMC1 and ParPMC2 are adjacent and highly homologous
      (87.5% identity) suggesting they are paralogs originated from a tandem
      duplication. Cultivars carrying the ParPMC2 resistant (mutated) allele show lack
      of expression in both ParPMC2 and especially ParPMC1. CONCLUSIONS: Accordingly,
      we hypothesize that ParPMC2 is a pseudogene that mediates down-regulation of its
      functional paralog ParPMC1 by silencing. As a whole, results strongly support
      ParPMC1 and/or ParPMC2 as host susceptibility genes required for PPV infection
      which silencing may confer PPV resistance trait. This finding may facilitate
      resistance breeding by marker-assisted selection and pave the way for gene
      edition approaches in Prunus.

PMID- 29374455
TI  - How patient participation was used to develop a questionnaire that is fit for
      purpose for assessing quality of life in severe asthma.
AB  - BACKGROUND: Previous research shows that existing asthma quality of life
      questionnaires fail to measure the burden of oral corticosteroids that can be
      used to treat severe asthma, and are therefore not fit for purpose for severe
      asthma according to the USA's Federal Drug Authority's (FDA) criteria for content
      validity. Patient input and documentation of that input is key to achieving
      content validity according to FDA guidelines. This paper describes the process of
      constructing a new questionnaire to measure the burden of asthma symptoms and
      burden of treatment in severe asthma, using criteria specified by the FDA.
      METHODS: A draft severe asthma questionnaire (SAQ) was constructed using
      qualitative input from severe asthma patients who took part in an earlier study.
      The aim of this study was to improve that draft questionnaire using a further
      group of patients. In four iterative focus groups, 16 people with severe asthma
      completed the draft questionnaire, discussed the wording and structure and
      suggested changes that were incorporated into the final version. RESULTS: The
      original intention to ask patients to identify whether problems were caused by
      asthma symptoms or side effects of medication was abandoned as the attribution of
      cause was found to be difficult and inconsistent. The recall period of 2 weeks
      was acceptable but fails to reflect the patients' desire to express the
      variability of severe asthma. Patients suggested improvements to the wording of
      the draft questionnaire, including splitting some items in two, combining two
      items in one, and changes to some of the words in individual items and the
      response scale. CONCLUSIONS: The final version of the questionnaire was
      substantially different from one constructed using only qualitative reports from
      patients about the quality of life deficits of severe asthma. Patients make a
      valuable contribution to the questionnaire if they are asked to comment and
      improve an initial draft and where patients are treated as partners in the
      process of questionnaire construction, rather than only as a source of
      information to experts who construct the questionnaire.

PMID- 29374456
TI  - Inbreeding and runs of homozygosity before and after genomic selection in North
      American Holstein cattle.
AB  - BACKGROUND: While autozygosity as a consequence of selection is well understood,
      there is limited information on the ability of different methods to measure true
      inbreeding. In the present study, a gene dropping simulation was performed and
      inbreeding estimates based on runs of homozygosity (ROH), pedigree, and the
      genomic relationship matrix were compared to true inbreeding. Inbreeding based on
      ROH was estimated using SNP1101, PLINK, and BCFtools software with different
      threshold parameters. The effects of different selection methods on ROH patterns
      were also compared. Furthermore, inbreeding coefficients were estimated in a
      sample of genotyped North American Holstein animals born from 1990 to 2016 using
      50 k chip data and ROH patterns were assessed before and after genomic selection.
      RESULTS: Using ROH with a minimum window size of 20 to 50 using SNP1101 provided
      the closest estimates to true inbreeding in simulation study. Pedigree inbreeding
      tended to underestimate true inbreeding, and results for genomic inbreeding
      varied depending on assumptions about base allele frequencies. Using an ROH
      approach also made it possible to assess the effect of population structure and
      selection on distribution of runs of autozygosity across the genome. In the
      simulation, the longest individual ROH and the largest average length of ROH were
      observed when selection was based on best linear unbiased prediction (BLUP),
      whereas genomic selection showed the largest number of small ROH compared to BLUP
      estimated breeding values (BLUP-EBV). In North American Holsteins, the average
      number of ROH segments of 1 Mb or more per individual increased from 57 in 1990
      to 82 in 2016. The rate of increase in the last 5 years was almost double that of
      previous 5 year periods. Genomic selection results in less autozygosity per
      generation, but more per year given the reduced generation interval. CONCLUSIONS:
      This study shows that existing software based on the measurement of ROH can
      accurately identify autozygosity across the genome, provided appropriate
      threshold parameters are used. Our results show how different selection
      strategies affect the distribution of ROH, and how the distribution of ROH has
      changed in the North American dairy cattle population over the last 25 years.

PMID- 29374457
TI  - Association between diabetes and pesticides: a case-control study among Thai
      farmers.
AB  - BACKGROUND: Pesticides are an agricultural chemical suspected to be a significant
      contributor to a global diabetes pandemic. The purpose of this study was to
      confirm previous findings of the link between diabetes and some agricultural
      pesticides and to identify the particular pesticides that are most likely to pose
      a risk of diabetes in the community. METHODS: A population-based case-controlled
      study was conducted among residents in the Bang Rakam district of Phitsanulok
      Province in Thailand. Lifetime pesticide exposure and other relevant data were
      collected from 866 participating cases with diabetes mellitus and 1021 healthy
      controls. RESULTS: After adjusting for gender, age, BMI, cigarette smoking,
      alcohol consumption, family history of diabetes, and occupation, it was found
      that the prevalence of diabetes was positively associated with exposure to all
      types of pesticides, including insecticides, herbicides, fungicides,
      rodenticides, and molluscicides, with exposure to rodenticides being
      statistically significant (OR = 1.35; 95%CI 1.04-1.76). Among 35 individual brand
      named pesticides investigated, we found statistically significant ORs with three
      insecticides, including one organochlorine [endosulfan (OR = 1.40; 95%CI 1.01
      1.95)], one organophosphate [mevinphos (OR = 2.22; 95%CI 1.17-4.19)], and one
      carbamate [carbaryl/Sevin (OR = 1.50; 95%CI 1.02-2.19)]; and one fungicides
      [benlate (OR = 2.08; 95%CI 1.03-4.20)]. CONCLUSIONS: Our results suggest that the
      occurrence of diabetes among Thai farmer was associated with pesticide exposure.
      This finding is in line with previous epidemiological and animal studies. Further
      study using a larger sample size is needed to confirm the relationship and to
      identify the more toxic compounds.

PMID- 29374458
TI  - Unique depot formed by an oil based vaccine facilitates active antigen uptake and
      provides effective tumour control.
AB  - BACKGROUND: Oil emulsions are commonly used as vaccine delivery platforms to
      facilitate slow release of antigen by forming a depot at the injection site.
      Antigen is trapped in the aqueous phase and as the emulsion degrades in vivo the
      antigen is passively released. DepoVaxTM is a unique oil based delivery system
      that directly suspends the vaccine components in the oil diluent that forces
      immune cells to actively take up components from the formulation in the absence
      of passive release. The aim of this study was to use magnetic resonance imaging
      (MRI) with additional biological markers to evaluate and understand differences
      in clearance between several different delivery systems used in peptide-based
      cancer vaccines. METHODS: C57BL/6 mice were implanted with a cervical cancer
      model and vaccinated 5 days post-implant with either DepoVax (DPX), a water-in
      oil emulsion (w/o), a squalene oil-in-water emulsion (squal o/w) or a
      saponin/liposome emulsion (sap/lip) containing iron oxide-labeled targeted
      antigen. MRI was then used to monitor antigen clearance, the site of injection,
      tumour and inguinal lymph node volumes and other gross anatomical changes. HLA-A2
      transgenic mice were also vaccinated to evaluate immune responses of human
      directed peptides. RESULTS: We demonstrated differences in antigen clearance
      between DPX and w/o both in regard to how quickly the antigen was cleared and the
      pattern in which it was cleared. We also found differences in lymph node
      responses between DPX and both squal o/w and sap/lip. CONCLUSIONS: These studies
      underline the unique mechanism of action of this clinical stage vaccine delivery
      system.

PMID- 29374459
TI  - Systemic air embolism after percutaneous computed tomography-guided lung biopsy
      due to a kink in the coaxial biopsy system: a case report.
AB  - BACKGROUND: Systemic air embolism is a rare but potentially life-threatening
      complication of percutaneous computed tomography (CT)-guided lung biopsy. The
      incidence might be underestimated because of failure to diagnose this adverse
      event in asymptomatic patients; early recognition is difficult. CASE
      PRESENTATION: We report the case of a 73-year-old man with systemic air embolism,
      a complication of percutaneous CT-guided lung biopsy, due to a kink in the
      coaxial biopsy system. Serial post-procedure CT scans demonstrated the causal
      relationship. CONCLUSIONS: Sequential post-biopsy CT scans demonstrated a causal
      relationship between this systemic air embolism and percutaneous biopsy, and
      allowed the radiologist to track the course of the emboli and their resolution.
      Awareness of air entry via the introducer needle and an early post-biopsy CT scan
      are crucial for early detection of systemic air embolism. If air embolism occurs
      in an asymptomatic patient, we recommend performing a delayed chest CT scan to
      follow the air's course.

PMID- 29374460
TI  - Precision and agreement of higher order aberrations measured with ray tracing and
      Hartmann-Shack aberrometers.
AB  - BACKGROUND: To assess the precision and agreement of measurements of higher order
      aberrations (HOAs) obtained with a ray tracing aberrometer (iTrace) and a
      Hartmann-Shack aberrometer (Topcon KR-1 W). METHODS: Prospective evaluation of
      the diagnostic test. Data from the right eyes of 92 normal subjects obtained
      using the two devices were included in this study. Two observers performed 3
      consecutive scans to determine the intraobserver repeatability and interobserver
      reproducibility. About one week later, one observer performed an additional 3
      consecutive scans to obtain the intersession reproducibility. The within-subject
      standard deviation (Sw), test-retest repeatability (TRT) and intraclass
      correlation coefficient (ICC) were used to assess the precision, while Bland
      Altman plots were performed to assess the agreement. RESULTS: For intraobserver
      repeatability of the ocular, corneal and internal HOAs, Topcon KR-1 W showed a
      2.77Sw of 0.079 MUm or less and ICCs of 0.761 or more; and iTrace showed a 2.77Sw
      of 0.105 MUm or less and ICCs of 0.805 or more. The ICCs of the internal HOAs of
      interobserver reproducibility were less than 0.75 except for spherical aberration
      (SA) (0.862), and interobserver reproducibility of the counterpart showed similar
      but lower results. For the ocular, corneal and internal HOA measurements,
      statistically significant differences existed between the Topcon KR-1 W and
      iTrace (all P < 0.05). No significant differences were observed in the ocular SA
      and internal coma. CONCLUSIONS: The ray tracing and Hartmann-Shack method
      aberrometers provided excellent repeatability but less reliable reproducibility
      in the measurement of HOAs (except for SA). The two aberrometers should not be
      interchangeable in clinical application because of the significant differences in
      HOA measurements between them.

PMID- 29374462
TI  - Community participation during two mass anti-malarial administrations in
      Cambodia: lessons from a joint workshop.
AB  - Two mass drug administrations (MDA) against falciparum malaria were conducted in
      2015-16, one as operational research in northern Cambodia, and the other as a
      clinical trial in western Cambodia. During an April 2017 workshop in Phnom Penh
      the field teams from Medecins Sans Frontieres and the Mahidol-Oxford Tropical
      Medicine Research Unit discussed lessons for future MDAs.

PMID- 29374461
TI  - Allele phasing is critical to revealing a shared allopolyploid origin of Medicago
      arborea and M. strasseri (Fabaceae).
AB  - BACKGROUND: Whole genome duplication plays a central role in plant evolution.
      There are two main classes of polyploid formation: autopolyploids which arise
      within one species by doubling of similar homologous genomes; in contrast,
      allopolyploidy (hybrid polyploidy) arise via hybridization and subsequent
      doubling of nonhomologous (homoeologous) genomes. The distinction between
      polyploid origins can be made using gene phylogenies, if alleles from each genome
      can be correctly retrieved. We examined whether two closely related tetraploid
      Mediterranean shrubs (Medicago arborea and M. strasseri) have an allopolyploid
      origin - a question that has remained unsolved despite substantial previous
      research. We sequenced and analyzed ten low-copy nuclear genes from these and
      related species, phasing all alleles. To test the efficacy of allele phasing on
      the ability to recover the evolutionary origin of polyploids, we compared these
      results to analyses using unphased sequences. RESULTS: In eight of the gene trees
      the alleles inferred from the tetraploids formed two clades, in a non-sister
      relationship. Each of these clades was more closely related to alleles sampled
      from other species of Medicago, a pattern typical of allopolyploids. However, we
      also observed that alleles from one of the remaining genes formed two clades that
      were sister to one another, as is expected for autopolyploids. Trees inferred
      from unphased sequences were very different, with the tetraploids often placed in
      poorly supported and different positions compared to results obtained using
      phased alleles. CONCLUSIONS: The complex phylogenetic history of M. arborea and
      M. strasseri is explained predominantly by shared allotetraploidy. We also
      observed that an increase in woodiness is correlated with polyploidy in this
      group of species and present a new possibility that woodiness could be a
      transgressive phenotype. Correctly phased homoeologues are likely to be critical
      for inferring the hybrid origin of allopolyploid species, when most genes retain
      more than one homoeologue. Ignoring homoeologous variation by merging the
      homoeologues can obscure the signal of hybrid polyploid origins and produce
      inaccurate results.

PMID- 29374463
TI  - Rapid conjugative mobilization of a 100 kb segment of Bacillus subtilis
      chromosomal DNA is mediated by a helper plasmid with no ability for self
      transfer.
AB  - BACKGROUND: The conjugative plasmid, pLS20, isolated from Bacillus subtilis
      natto, has an outstanding capacity for rapid self-transfer. In addition, it can
      function as a helper plasmid, mediating the mobilization of an independently
      replicating co-resident plasmid. RESULTS: In this study, the oriT sequence of
      pLS20cat (oriTLS20) was eliminated to obtain the plasmid, pLS20catDeltaoriT. This
      resulted in the complete loss of the conjugative transfer of the plasmid but
      still allowed it to mobilize a co-resident mobilizable plasmid. Moreover,
      pLS20catDeltaoriT was able to mobilize longer DNA segments, up to 113 kb of
      chromosomal DNA containing oriTLS20, after mixing the liquid cultures of the
      donor and recipient for only 15 min. CONCLUSIONS: The chromosomal DNA
      mobilization mediated by pLS20catDeltaoriT will allow us to develop a novel
      genetic tool for the rapid, easy, and repetitive mobilization of longer DNA
      segments into a recipient chromosome.

PMID- 29374464
TI  - Disseminated cryptococcosis presenting initially as lower limb cellulitis in a
      renal transplant recipient - a case report.
AB  - BACKGROUND: Cellulitis is an unusual presentation of disseminated cryptococcosis,
      a serious infection seen predominantly in immunocompromised hosts. Disseminated
      cryptococcosis carries significant morbidity for transplant recipients,
      especially of the pulmonary and central nervous systems, and carries a high
      mortality risk. CASE PRESENTATION: We report a 59-year-old renal transplant
      recipient who presented with bilateral lower leg cellulitis without other
      symptoms or signs. Failure of conventional therapy for cellulitis prompted a skin
      biopsy confirming cryptococcal cellulitis. Additional evaluation to exclude
      disseminated disease revealed Cryptococcus neoformans in blood cultures and
      cerebrospinal fluid (CSF). Treatment included reduction in immunosuppression
      regimen and targeted treatment for cryptococcal disease with liposomal
      amphotericin B and flucytosine followed by fluconazole consolidation and
      maintenance therapy. Treatment with liposomal amphotericin B and flucytosine
      followed by fluconazole consolidation and maintenance therapy achieved a good
      clinical response. Our patient achieved significant reduction in leg cellulitis
      and recovered without serious complication. CONCLUSIONS: This case suggests that
      cutaneous cryptococcosis in immunosuppressed patients warrants a low threshold
      for investigation for disseminated disease even in the absence of other symptoms
      or signs.

PMID- 29374465
TI  - Penetrating aortic injury left untreated for 20 days: a case report.
AB  - BACKGROUND: Penetrating aortic trauma remains one of the most challenging
      injuries with a high mortality rate if left untreated, or if the surgical
      treatment is delayed. We present an uncommon case of a late diagnosed abdominal
      firearm injury, in which the bullet partially penetrated the wall of the aorta,
      creating a plug that prevented immediate death due to massive bleeding. CASE
      PRESENTATION: A 26-year-old Libyan man was a victim of a firearm wound, with a
      bullet penetrating his abdominal wall from the left to right side. After the
      assault, the victim, spent up to 20 days crossing the Mediterranean Sea to leave
      his country of origin. Abdominal radiography revealed the presence of a bullet
      located anteriorly to the second lumbar vertebra, while computed tomography
      angiography, unexpectedly, demonstrated that the bullet penetrated partially into
      the aortic wall at the level of the left renal artery. The bullet penetrated the
      aortic wall for half of its length, creating a plug that avoided immediate life
      threatening bleeding at the time of the gunshot injury. The bullet was removed
      and the aortic lesion was repaired. The patient was discharged 6 days after the
      surgical procedure, in good health. CONCLUSIONS: We presented a very rare case of
      late diagnosis of aortic injury caused by a gunshot lesion, in which the
      particular trajectory of the bullet helped avoid immediate life-threatening
      bleeding and, probably, saved the patient's life.

PMID- 29374466
TI  - Case report: a fatal case of disseminated adenovirus infection in a non
      transplant adult haematology patient.
AB  - BACKGROUND: We report a fatal case of disseminated adenovirus infection in a non
      transplant haematology adult patient with chronic lymphocytic leukaemia who had
      completed combination chemoimmunotherapy a few months before developing
      respiratory symptoms. In such non-transplant patients, monitoring for adenovirus
      in the blood is not routine. However, with adenoviruses, when there is a more
      peripheral (i.e. non-blood) site of infection such as the chest, serial
      adenovirus monitoring in blood for the duration of that illness may be warranted.
      CASE PRESENTATION: This case started with an initial bacterial chest infection
      that responded to treatment, followed by an adenovirus pneumonitis that
      disseminated to his blood a week later with levels of up to 92 million adenovirus
      DNA copies/ml. Despite prompt treatment with cidofovir, his respiratory function
      continued to deteriorate over the next two weeks and he was moved to intensive
      care. Intravenous immunoglobulin and ribavirin were subsequently added to his
      treatment. However, he died soon after this with a final adenovirus load of 20
      million copies/ml in his blood. CONCLUSIONS: We recommend that even in non
      transplant haematology patients, where such patients present with an acute
      respiratory adenovirus infection, teams should consider checking the blood for
      adenovirus to check for signs of disseminated infection. The earlier this can be
      tested, the earlier treatment can be initiated (if adenovirus positive), which
      may produce more successful clinical outcomes.

PMID- 29374467
TI  - The global switch from trivalent oral polio vaccine (tOPV) to bivalent oral polio
      vaccine (bOPV): facts, experiences and lessons learned from the south-south zone;
      Nigeria, April 2016.
AB  - BACKGROUND: The globally synchronized switch from trivalent Oral Polio Vaccine
      (tOPV) to bivalent Oral Polio Vaccine (bOPV) took place in Nigeria on April 18th
      2016. The country is divided into six geopolitical zones. This study reports the
      experiences and lessons learned from the switch process in the six states that
      make up Nigeria's south-south geopolitical zone. METHODS: This was a descriptive
      retrospective review of Nigeria's switch plan and structures used for
      implementing the tOPV-bOPV switch in the south-south zone. Nigeria's National
      Polio Emergency Operation Centre (NPEOC) protocols, global guidelines and reports
      from switch supervisors during the switch were used to provide background
      information for this study. Quantitative data were derived from reviewing switch
      monitoring and validation documents as submitted to the NPEOC RESULTS: The switch
      process took place in all 3078 Health Facilities (HFs) and 123 Local Government
      Areas (LGAs) that make up the six states in the zone. A total of $139,430 was
      used for this process. The 'healthcare personnel' component received the highest
      budgetary allocation (59%) followed by the 'logistics' component (18%). Akwa Ibom
      state was allocated the highest number of healthcare personnel and hence received
      the most budgetary allocation compared to the six states (total healthcare
      personnel = 458, total budgetary allocation = $17,428). Validation of the switch
      process revealed that eight HFs in Bayelsa, Cross-River, Edo and Rivers states
      still possessed tOPV in cold-chain while six HFs in Cross-River and Rivers states
      had tOPV out of cold-chain but without the 'do not use' sticker. Akwa-Ibom was
      the only state in the zone to have bOPV and Inactivated Polio Vaccine (IPV)
      available in all its HFs monitored. CONCLUSION: The Nigerian tOPV-bOPV switch was
      successful. For future Oral Polio Vaccine (OPV) withdrawals, implementation of
      the switch plan would be more feasible with an earlier dissemination of funds
      from global donor organizations, which would greatly aid timely planning and
      preparations. Increased budgetary allocation to the 'logistics' component to
      accommodate unexpected hikes in transportation prices and the general
      inefficiencies with power supply in the country is also advised.

PMID- 29374468
TI  - Chronic kidney disease alters lipid trafficking and inflammatory responses in
      macrophages: effects of liver X receptor agonism.
AB  - BACKGROUND: Our aim was to evaluate lipid trafficking and inflammatory response
      of macrophages exposed to lipoproteins from subjects with moderate to severe
      chronic kidney disease (CKD), and to investigate the potential benefits of
      activating cellular cholesterol transporters via liver X receptor (LXR) agonism.
      METHODS: LDL and HDL were isolated by sequential density gradient
      ultracentrifugation of plasma from patients with stage 3-4 CKD and individuals
      without kidney disease (HDLCKD and HDLCont, respectively). Uptake of LDL,
      cholesterol efflux to HDL, and cellular inflammatory responses were assessed in
      human THP-1 cells. HDL effects on inflammatory markers (MCP-1, TNF-alpha, IL
      1beta), Toll-like receptors-2 (TLR-2) and - 4 (TLR-4), ATP-binding cassette class
      A transporter (ABCA1), NF-kappaB, extracellular signal regulated protein kinases
      1/2 (ERK1/2) were assessed by RT-PCR and western blot before and after in vitro
      treatment with an LXR agonist. RESULTS: There was no difference in macrophage
      uptake of LDL isolated from CKD versus controls. By contrast, HDCKD was
      significantly less effective than HDLCont in accepting cholesterol from
      cholesterol-enriched macrophages (median 20.8% [IQR 16.1-23.7] vs control (26.5%
      [IQR 19.6-28.5]; p = 0.008). LXR agonist upregulated ABCA1 expression and
      increased cholesterol efflux to HDL of both normal and CKD subjects, although the
      latter continued to show lower efflux capacity. HDLCKD increased macrophage
      cytokine response (TNF-alpha, MCP-1, IL-1beta, and NF-kappaB) versus HDLCont. The
      heightened cytokine response to HDLCKD was further amplified in cells treated
      with LXR agonist. The LXR-augmentation of inflammation was associated with
      increased TLR-2 and TLR-4 and ERK1/2. CONCLUSIONS: Moderate to severe impairment
      in kidney function promotes foam cell formation that reflects impairment in
      cholesterol acceptor function of HDLCKD. Activation of cellular cholesterol
      transporters by LXR agonism improves but does not normalize efflux to HDLCKD.
      However, LXR agonism actually increases the pro-inflammatory effects of HDLCKD
      through activation of TLRs and ERK1/2 pathways.

PMID- 29374469
TI  - Perioperative incidence of airway obstructive and hypoxemic events in patients
      with confirmed or suspected sleep apnea - a prospective, randomized pilot study
      comparing propofol/remifentanil and sevoflurane/remifentanil anesthesia.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for perioperative
      complications but data on anesthesia regimen are scarce. METHODS: In patients
      with established or strongly suspected OSA, we assessed in a prospective,
      randomized design the effects on nocturnal apnea-hypopnea-index (AHI) and oxygen
      saturation (SpO2) of propofol/remifentanil or sevoflurane/remifentanil based
      anesthesia. Patients were selected by a history for OSA and / or a positive STOP 
      questionnaire and received general anesthesia using remifentanil (12 MUg/kg/h)
      combined either with propofol (4-6 mg/kg/h, n = 27) or sevoflurane (approx. 2.2
      vol% endtidal, n = 27). AHI and SpO2 were measured during the nights before and
      after anesthesia. RESULTS: There were no differences in AHI between anesthetic
      regimens nor between the pre- and postoperative nights (propofol: 8.6 h- 1
      (median, CI: 3.6-21.9) vs. 7.9 h- 1 (1.8-28.8); p = 0.97; sevoflurane: 3.8 h- 1
      (1.8-7.3) vs. 2.9 h- 1 (1.2-9.5); p = 0.85). Postoperative minimum SpO2
      (propofol: 80.7% +/- 4.6, sevoflurane: 81.6 +/- 4.6) did not differ from their
      respective preoperative baselines (propofol: 79.6% +/- 6.5; p = 0.26,
      sevoflurane: 80.8% +/- 5.2; p = 0.39). Even in patients with a preanesthetic AHI
      > 15, nocturnal AHI remained unchanged postoperatively. CONCLUSION: Thus, in a
      cohort of patients with suspected or confirmed OSA undergoing surgery of moderate
      duration and severity neither the volatile agent sevoflurane nor the intravenous
      anesthetic propofol altered nocturnal AHI or oxygen saturation, when combined
      with the short acting opioid remifentanil. TRIAL REGISTRATION: German Clinical
      Trials Register, DRKS00005824 retrospectively registered on 03/12/2014.

PMID- 29374470
TI  - Association of thyroid nodules with adiposity: a community-based cross-sectional
      study in China.
AB  - BACKGROUND: The association between thyroid nodules and adiposity remains
      controversial. We performed a cross-sectional, community-based study to examine
      whether thyroid nodules are associated with overweight and obesity, as defined
      with body mass index (BMI) and waist circumference. METHODS: The study included
      1482 subjects (>=20 years of age; residing in Nanjing, China) receiving
      questionnaire interview, anthropometric measurements, laboratory tests and
      thyroid ultrasonography in 2009-2010. Overweight and obesity were defined as BMI
      >=24 and >=28 kg/m2, respectively. Central obesity was defined as waist
      circumference at >=90 cm in men and >=80 cm in women. A sensitivity analysis was
      conducted using the American Diabetes Association (ADA) criteria for overweight
      and obesity (BMI >= 23 and >=25 kg/m2). RESULTS: Thyroid nodules were identified
      in 12.6% of the subjects. A greater proportion of the subjects with thyroid
      nodules had a BMI at >=24 kg/m2 (51.9% vs. 40.5% in those without thyroid
      nodules, P = 0.003) and central obesity (43.3% vs. 24.2%, P < 0.001). After
      adjustment for other confounders, central obesity was still associated with
      significantly elevated risk of thyroid nodules (OR 1.62, 95%CI 1.14-2.28),
      whereas obesity/overweight based on BMI was not in both the main analysis and
      sensitivity analysis with the alternative criteria. In the subgroup analysis, BMI
      >=24 kg/m2 (OR 1.61, 95%CI 1.01-2.54), as well as BMI >=25 kg/m2 (OR 1.95, 95%CI
      1.14-3.34), was significantly associated with higher risk of thyroid nodules
      among women. Using the ADA criteria, overweight and obesity were associated with
      thyroid nodules (OR 5.59, 95%CI 1.39-22.51 and 5.15, 95%CI 1.30-20.37) in thyroid
      stimulating hormone (TSH) > 4.2 mIU/L subgroup. Central obesity correlated with
      higher risk of thyroid nodules regardless of age (< 50 years: OR 1.87, 95%CI 1.05
      3.32: >=50 years: OR 1.54, 95%CI 1.00-2.37) and in the following subgroups: men
      (OR 1.91, 95%CI 1.14-3.20), TSH > 4.2 mIU/L (OR 3.05, 95%CI 1.01-9.22), and urine
      iodine >=200 ug/L (OR 1.79, 95%CI 1.14-2.81). CONCLUSION: Waist circumference is
      superior to BMI for assessing risk of thyroid nodules in Chinese subjects.

PMID- 29374471
TI  - Subchronic toxicity, immunoregulation and anti-breast tumor effect of
      Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia
      L.
AB  - BACKGROUND: Morinda citrifolia L. that was reported with immunomodulating and
      cytotoxic effects has been traditionally used to treat multiple illnesses
      including cancer. An anthraquinone derived from fruits of Morinda citrifolia L.,
      nordamnacanthal, is a promising agent possessing several in vitro biological
      activities. However, the in vivo anti-tumor effects and the safety profile of
      nordamnacanthal are yet to be evaluated. METHODS: In vitro cytotoxicity of
      nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human
      MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with
      nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the
      in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged
      mice. Changes of tumor size and immune parameters were evaluated on the untreated
      and nordamnacanthal treated mice. RESULTS: Nordamnacanthal was found to possess
      cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on
      the cell cycle and Annexin V results, nordamnacanthal managed to induce cell
      death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of
      toxicity and changes of serum liver profile were observed in nordamnacanthal
      treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight
      of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C
      mice after 28 days of treatment. Treatment with nordamnacanthal was also able to
      increase tumor immunity as evidenced by the immunophenotyping of the spleen and
      YAC-1 cytotoxicity assays. CONCLUSION: Nordamnacanthal managed to inhibit the
      growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease
      the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds
      interesting anti-cancer properties that can be further explored.

PMID- 29374472
TI  - Exploring health care seeking knowledge, perceptions and practices for childhood
      diarrhea and pneumonia and their context in a rural Pakistani community.
AB  - BACKGROUND: Where access to facilities for childhood diarrhea and pneumonia is
      inadequate, community case management (CCM) is an effective way of improving
      access to care. In Pakistan, utilization of CCM for these diseases through the
      Lady Health Worker Program remains low. Challenges of access to facilities
      persist leading to delayed care and poor outcomes. Estimating caregiver
      knowledge, understanding their perceptions and practices, and recognizing how
      these are related to care seeking decisions about childhood diarrhea and
      pneumonia is crucial to bring about coherence between supply and demand-side
      practices. METHODS: Data was collected from family caregivers to explore their
      knowledge, perceptions and practices regarding childhood diarrhea and pneumonia.
      Data from a household survey with 7025 caregivers, seven focus group discussion
      (FGDs), seven in-depth interviews (IDIs), and 20 detailed narrative interviews
      are used to explore caregiver knowledge, perceptions and practices. RESULTS:
      Household survey shows that most family caregivers recognize main signs and
      symptoms of diarrhea such as loose stools (76%). Fewer recognize signs and
      symptoms of pneumonia such as breathing problems (21%). Few caregivers (18%) have
      confidence in lady health workers' (LHWs) ability to treat childhood diarrhea and
      pneumonia. Care seeking from LHWs remains negligible (< 1%). Caregivers
      overwhelmingly prefer to seek care from doctors (97%). Seventy-five percent
      caregivers sought care from private providers and 45% from public providers.
      FGDs, IDIs, and narrative interviews show that care mostly begins with home
      remedies and sometimes self-prescribed medicines. Treatment delays occur because
      of caregiver inability to recognize disease, use of home remedies, financial
      constraints, and low utilization of community based LHW services. Caregivers do
      not seek care from LHWs because of lack of trust and LHWs' inability to provide
      medicines. If finances allow, private doctors, who caregivers perceive as more
      responsive, are preferred over public sector doctors. Financial resources,
      availability of time, support for household chores by family and community
      determine whether, when, and from whom caregivers seek care. CONCLUSIONS: Many
      children do not receive recommended diarrhea and pneumonia treatment on time.
      Taking into consideration caregiver concerns, adequate supply of medicines to
      LHWs, improved facility level care could improve care seeking practices and child
      health outcomes. TRIAL REGISTRATION: The trial is registered with 'Australian New
      Zealand Clinical Trials Registry'. Registration Number: ACTRN12613001261707 .
      Registered 18 November 2013.

PMID- 29374473
TI  - Epidemiology of gastrointestinal symptoms in young and middle-aged Swiss adults:
      prevalences and comorbidities in a longitudinal population cohort over 28 years.
AB  - BACKGROUND: Although subacute and chronic gastrointestinal symptoms are very
      common in primary care, epidemiological date are sparse. The aim of the study was
      to examine and quantify the prevalence of subacute and chronic gastrointestinal
      symptoms and their associations with somatic and mental disorders in the general
      population. METHODS: Data were collected prospectively between 1981 (age m = 22,
      f = 23) and 2008 (age 49/50) from the Zurich Cohort Study (n = 292 men, 299
      women), a representative general population survey. The participants were
      assessed using a semi-structured interview, the "Structured Psychopathological
      Interview and Rating of the Social Consequences of Psychological Disturbances for
      Epidemiology" (SPIKE). Prevalence rates were computed to be representative of the
      general population aged 22-50. Associations were quantified by odds ratios (ORs)
      and their 99% confidence intervals (CI). RESULTS: The prevalences of intestinal
      and of gastric symptoms were significantly higher among women in all categories
      examined. For example, any gastric symptoms: f. 26.4% vs m.15.2%; any intestinal
      symptoms: 27.6% vs 14.6%; nausea/vomitus: 19.1% vs 4.5%; constipation: 15.8% vs
      6.5% (all p < 0.001). Strong associations (all p < 0.0001) were found between
      fatigue (1 month) and chronic stomach (OR = 9.96, 99%-CI: 5.53-17.94) and chronic
      intestinal symptoms (OR = 9.02, 99%-CI: 4.92-16.54). Panic attacks were
      associated with subacute intestinal symptoms (OR = 4.00, 99%-CI: 2.43-6.59).
      Anxiety was more strongly associated with subacute intestinal symptoms (OR =
      3.37, 99%-CI: 2.23-5.08) than with subacute stomach symptoms (OR = 1.85, 1.20
      2.86). Bipolar disorders were associated with subacute stomach symptoms (OR =
      1.83, 1.18-2.17) and unipolar depression with subacute intestinal symptoms (OR =
      2.05, 1.34-3.15). CONCLUSIONS: Remarkably high prevalence rates of gastric and
      intestinal complaints were observed in women (over 1/4; men 1/7).
      Fatigue/neurasthenia was the strongest co-factor in both conditions. Various
      syndromes related to anxiety, phobia, and panic disorders showed further
      significant associations. The integration of psychiatric and/or psychological
      treatment could help address the functional part of gastric and intestinal
      syndromes.

PMID- 29374474
TI  - GenIO: a phenotype-genotype analysis web server for clinical genomics of rare
      diseases.
AB  - BACKGROUND: GenIO is a novel web-server, designed to assist clinical genomics
      researchers and medical doctors in the diagnostic process of rare genetic
      diseases. The tool identifies the most probable variants causing a rare disease,
      using the genomic and clinical information provided by a medical practitioner.
      Variants identified in a whole-genome, whole-exome or target sequencing studies
      are annotated, classified and filtered by clinical significance. Candidate genes
      associated with the patient's symptoms, suspected disease and complementary
      findings are identified to obtain a small manageable number of the most probable
      recessive and dominant candidate gene variants associated with the rare disease
      case. Additionally, following the American College of Medical Genetics and
      Genomics and the Association of Molecular Pathology (ACMG-AMP) guidelines and
      recommendations, all potentially pathogenic variants that might be contributing
      to disease and secondary findings are identified. RESULTS: A retrospective study
      was performed on 40 patients with a diagnostic rate of 40%. All the known genes
      that were previously considered as disease causing were correctly identified in
      the final inherit model output lists. In previously undiagnosed cases, we had no
      additional yield. CONCLUSION: This unique, intuitive and user-friendly tool to
      assists medical doctors in the clinical genomics diagnostic process is openly
      available at https://bioinformatics.ibioba-mpsp-conicet.gov.ar/GenIO/ .

PMID- 29374475
TI  - Prediction of HIV-associated neurocognitive disorder (HAND) from three genetic
      features of envelope gp120 glycoprotein.
AB  - BACKGROUND: HIV-associated neurocognitive disorder (HAND) remains an important
      and yet potentially underdiagnosed manifestation despite the fact that the modern
      combination antiretroviral therapy (cART) has achieved effective viral
      suppression and greatly reduced the incidence of life-threatening events.
      Although HIV neurotoxicity is thought to play a central role, the potential of
      viral genetic signature as diagnostic and/or prognostic biomarker has yet to be
      fully explored. RESULTS: Using a manually curated sequence metadataset (80
      specimens, 2349 sequences), we demonstrated that only three genetic features are
      sufficient to predict HAND status regardless of sampling tissues; the accuracy
      reached 100 and 94% in the hold-out testing subdataset and the entire dataset,
      respectively. The three genetic features stratified HAND into four distinct
      clusters. Extrapolating the classification to the 1619 specimens registered in
      the Los Alamos HIV Sequence Database, the global HAND prevalence was estimated to
      be 46%, with significant regional variations (30-71%). The R package
      HANDPrediction was implemented to ensure public availability of key codes.
      CONCLUSIONS: Our analysis revealed three amino acid positions in gp120
      glycoprotein, providing the basis of the development of novel cART regimens
      specifically optimized for HAND-associated quasispecies. Moreover, the classifier
      can readily be translated into a diagnostic biomarker, warranting prospective
      validation.

PMID- 29374476
TI  - Extracellular vesicle-derived DNA for performing EGFR genotyping of NSCLC
      patients.
AB  - Tumor cells shed an abundance of extracellular vesicles (EVs) to body fluids
      containing bioactive molecules including DNA, RNA, and protein. Investigations in
      the field of tumor-derived EVs open a new horizon in understanding cancer biology
      and its potential as cancer biomarkers as well as platforms for personalized
      medicine. This study demonstrates that successfully isolated EVs from plasma and
      bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC)
      patients contain DNA that can be used for EGFR genotyping through liquid biopsy.
      In both plasma and BALF samples, liquid biopsy results using EV DNA show higher
      accordance with conventional tissue biopsy compared to the liquid biopsy of
      cfDNA. Especially, liquid biopsy with BALF EV DNA is tissue-specific and
      extremely sensitive compared to using cfDNA. Furthermore, use of BALF EV DNA also
      demonstrates higher efficiency in comparison to tissue rebiopsy for detecting
      p.T790 M mutation in the patients who developed resistance to EGFR-TKIs. These
      finding demonstrate possibility of liquid biopsy using EV DNA potentially
      replacing the current diagnostic methods for more accurate, cheaper, and faster
      results.

PMID- 29374477
TI  - Epoetin beta pegol for treatment of anemia ameliorates deterioration of
      erythrocyte quality associated with chronic kidney disease.
AB  - BACKGROUND: Epoetin beta pegol (continuous erythropoietin receptor activator;
      C.E.R.A.) is currently widely used for the treatment of anemia associated with
      chronic kidney disease (CKD). Therapeutic control of anemia is assessed by
      monitoring haemoglobin (Hb) levels. However, certain qualitative aspects of
      erythrocytes are also impaired in CKD, including loss of deformability and
      shortened life-span. Therefore, monitoring Hb alone could potentially fail to
      reveal pathological changes in erythrocytes. Focusing on erythrocyte quality in
      CKD may lead to more effective anemia therapy with C.E.R.A. METHODS: A CKD rat
      model was induced by uninephrectomy followed by anti-Thy1.1 antibody injection.
      From 5 weeks after the operation, C.E.R.A. (0.6 MUg/kg) or vehicle was
      administered every 2 weeks. Erythrocyte deformability was quantified with
      ektacytometry and erythrocyte turnover was estimated by biotin labeling.
      Intracellular calcium level was assessed by Fluo-3/AM. RESULTS: Erythrocyte
      deformability progressively declined in CKD rats. Furthermore, erythrocyte
      turnover in the circulation drastically accelerated in CKD rats. With
      administration of C.E.R.A. at a dose sufficient to adequately control Hb,
      deterioration of erythrocyte deformability and turnover in CKD rats were
      significantly improved. Intracellular calcium, which plays a pivotal role in the
      mediation of erythrocyte quality, was significantly increased in CKD and was
      normalized by C.E.R.A. TREATMENT:  CONCLUSION: C.E.R.A. treatment exerted a
      favorable effect not only on anemia but also on the improvement of erythrocyte
      quality. C.E.R.A. administered for the treatment of CKD-associated anemia may
      confer therapeutic benefits on erythrocytes.

PMID- 29374478
TI  - Operation and challenges of home-based medical practices in the US: findings from
      six aggregated case studies.
AB  - BACKGROUND: Home-based primary care (HBPC) is a multidisciplinary, ongoing care
      strategy that can provide cost-effective, in-home treatment to meet the needs of
      the approximately four million homebound, medically complex seniors in the U.S.
      Because there is no single model of HBPC that can be adopted across all types of
      health organizations and U.S. geographic regions, we conducted a six-site HBPC
      practice assessment to better understand different operation structures, common
      challenges, and approaches to delivering HBPC. METHODS: Six practices varying in
      size, care team composition and location agreed to participate. At each site we
      conducted unstructured interviews with key informants and directly observed
      practices and procedures in the field and back office. RESULTS: The aggregated
      case studies revealed important issues focused on team composition, patient
      characteristics, use of technology and urgent care delivery. Common challenges
      across the practices included provider retention and unmet community demand for
      home-based care services. Most practices, regardless of size, faced challenges
      around using electronic medical records (EMRs) and scheduling systems not
      designed for use in a mobile practice. Although many practices offered urgent
      care, practices varied in the methods used to provide care including the use of
      community paramedics and telehealth technology. CONCLUSIONS: Learnings compiled
      from these observations can inform other HBPC practices as to potential best
      practices that can be implemented in an effort to improve efficiency and
      scalability of HBPC so that seniors with multiple chronic conditions can receive
      comprehensive primary care services in their homes.

PMID- 29374479
TI  - Determinants of adolescent pregnancy in sub-Saharan Africa: a systematic review.
AB  - BACKGROUND: Adolescent pregnancy has been persistently high in sub-Saharan
      Africa. The objective of this review is to identify factors influencing
      adolescent pregnancies in sub-Saharan Africa in order to design appropriate
      intervention program. METHODS: A search in MEDLINE, Scopus, Web of science, and
      Google Scholar databases with the following keywords: determinants, factors,
      reasons, sociocultural factors, adolescent pregnancy, unintended pregnancies, and
      sub- Saharan Africa. Qualitative and cross-sectional studies intended to assess
      factors influencing adolescent pregnancies as the primary outcome variable in sub
      Saharan Africa were included. Our search was limited to, articles published from
      the year 2000 to 2017 in English. Twenty-four (24) original articles met the
      inclusion criteria. RESULTS: The study identified Sociocultural, environmental
      and Economic factors (Peer influence, unwanted sexual advances from adult males,
      coercive sexual relations, unequal gender power relations, poverty, religion,
      early marriage, lack of parental counseling and guidance, parental neglect,
      absence of affordable or free education, lack of comprehensive sexuality
      education, non-use of contraceptives, male's responsibility to buy condoms, early
      sexual debut and inappropriate forms of recreation). Individual factors
      (excessive use of alcohol, substance abuse, educational status, low self-esteem,
      and inability to resist sexual temptation, curiosity, and cell phone usage).
      Health service-related factors (cost of contraceptives, Inadequate and unskilled
      health workers, long waiting time and lack of privacy at clinics, lack of
      comprehensive sexuality education, misconceptions about contraceptives, and non
      friendly adolescent reproductive services,) as influencing adolescent pregnancies
      in Sub-Saharan Africa CONCLUSION: High levels of adolescent pregnancies in Sub
      Saharan Africa is attributable to multiple factors. Our study, however,
      categorized these factors into three major themes; sociocultural and economic,
      individual, and health service related factors as influencing adolescent
      pregnancies. Community sensitization, comprehensive sexuality education and
      ensuring girls enroll and stay in schools could reduce adolescent pregnancy
      rates. Also, provision of adolescent-friendly health services in schools and
      healthcare centers and initiating adolescent empowerment programs could have a
      positive impact.

PMID- 29374480
TI  - The challenges of interventions to promote healthier food in independent
      takeaways in England: qualitative study of intervention deliverers' views.
AB  - BACKGROUND: Much of the food available from takeaways, pubs and restaurants
      particularly that sold by independent outlets, is unhealthy and its consumption
      is increasing. These food outlets are therefore important potential targets for
      interventions to improve diet and thus prevent diet related chronic diseases.
      Local authorities in England have been charged with delivering interventions to
      increase the provision of healthy food choices in independent outlets, but prior
      research shows that few such interventions have been rigorously developed or
      evaluated. We aimed to learn from the experiences of professionals delivering
      interventions in independent food outlets in England to identify the operational
      challenges and their suggestions for best practice. METHODS: We used one-to-one
      semi-structured qualitative interviews to explore the views and experiences of
      professionals who were either employees of, or contracted by, a local authority
      to deliver interventions to increase the provision of healthier food choices in
      independent food outlets. Purposive sampling was used to recruit a sample which
      included men and women, from a range of professional roles, across different
      areas of England. Interviews were informed by a topic guide, and proceeded until
      no new themes emerged. Interviews were recorded, transcribed verbatim and
      analysed using the Framework method. RESULTS: We conducted 11 individual
      interviews. Participants focussed on independent takeaways and their unhealthy
      food offerings, and highlighted the advantages and disadvantages of intervention
      delivery methods, their evaluation and impact. The main barriers to
      implementation of interventions in independent takeaways were identified as
      limited funding and the difficulties of engaging the food outlet owner/manager.
      Engagement was thought to be facilitated by delivering intensive, interactive and
      tailored interventions, clear and specific information, and incentives, whilst
      accounting for practical, primarily financial, constraints of food businesses.
      Alternative intervention approaches, targeting suppliers or customers, were
      suggested. CONCLUSIONS: Participants emphasised independent takeaways as
      particularly challenging, but worthwhile intervention targets. Participants
      perceived that interventions need to take account of the potentially challenging
      operating environment, particularly the primacy of the profit motive. Upstream
      interventions, engaging suppliers, as well as those that drive consumer demand,
      may be worth exploring. Rigorous, evidence-informed development and evaluation of
      such interventions is needed.

PMID- 29374481
TI  - Use of health services according to income before and after elimination of
      copayment in Germany and restriction of universal health coverage in Spain.
AB  - BACKGROUND: In Germany copayment for medical consultation was eliminated in 2013,
      and in Spain universal health coverage was partly restricted in 2012. This study
      shows the relationship between income and the use of health services before and
      after these measures in each country. METHODS: Data were taken from the 2009 and
      2014 Socio-Economic Panel conducted in Germany, and from the 2009 and 2014
      European Health Surveys in Spain. The health services investigated were physician
      consultations and hospital admissions, and the measure of socioeconomic position
      used was household income. The magnitude of the relationship between
      socioeconomic position and the use of each health service in people from 16 to 74
      years old was estimated by calculating the percentage ratio using binary
      regression. RESULTS: In Germany, after adjusting for age, sex, and need for care,
      in the model comparing the two lower income categories to the two higher
      categories, the percentage ratio for physician consultation was 0.97 (95% CI 0.96
      0.99) in 2009 and 0.98 (95% CI 0.97-0.99) in 2014, and the percentage ratio for
      hospitalization was 1.01 (95% CI 0.93-1.10) in 2009 and 1.16 (95% CI 1.08-1.25)
      in 2014. In Spain, after adjusting for age, sex, and self-rated health, the
      percentage ratio for physician consultation was 0.99 (95% CI 0.94-1.05) in 2009
      and 1.08 (95% CI 1.03-1.14) in 2014, and the percentage ratio for hospitalization
      was 1.04 (95% CI 0.92-1.18) in 2009 and 0.99 (95% CI 0.87-1.14) in 2014.
      CONCLUSION: The results suggest that elimination of the copayment in Germany did
      not change the frequency of physician consultations, whereas after the
      restriction of universal health coverage in Spain, subjects with lower incomes
      had a higher frequency of physician consultations.

PMID- 29374482
TI  - What is known about pathways to mental health care for Australian Aboriginal
      young people?: a narrative review.
AB  - OBJECTIVES: To (1) gain an understanding of current trajectories of Aboriginal
      young people through the mental health care system in Australia; (2) summarize
      what mental health care pathways have been developed or evaluated to guide mental
      health care delivery for Aboriginal young people; and (3) identify barriers and
      facilitators to the adoption of effective mental health care pathways for
      Aboriginal young people. METHODS: Databases, including, AMED, Embase, Global
      Health, Health and Psychosocial Instruments, Healthstar, MEDLINE, PsychINFO via
      Ovid, CINAHL via EBSCO, The Cochrane Library, Indigenous Collections, Informit
      and Health Systems Evidence, were searched to identify evidence concerning mental
      health service delivery for Aboriginal young people in a primary care setting.
      RESULTS: We did not identify any reports or publications explicitly describing
      the current trajectories of Aboriginal young people through the mental health
      care system in Australia. Furthermore, we were unable to locate any mental health
      related treatment pathways which had been explicitly developed or modified to
      meet the needs of Aboriginal young people. The use of appropriate assessment
      tools, engagement of family and community, flexibility, and central coordination
      have been identified in the literature as potential facilitators of culturally
      appropriate mental health service delivery for Aboriginal children and
      adolescents. CONCLUSIONS: Aboriginal children and adolescents may face additional
      difficulties navigating the mental health care system in Australia due to complex
      socio-cultural factors and the dearth of culturally appropriate and effective
      mental-health related treatment pathways. Additional research regarding (1)
      practice trends in Aboriginal settings and (2) how Aboriginal child and
      adolescent mental health can be improved is urgently needed to inform clinical
      practice and improve mental health service access and outcomes for Aboriginal
      young people in Australia.

PMID- 29374483
TI  - Engineering E. coli for simultaneous glucose-xylose utilization during methyl
      ketone production.
AB  - BACKGROUND: We previously developed an E. coli strain that overproduces medium
      chain methyl ketones for potential use as diesel fuel blending agents or as
      flavors and fragrances. To date, the strain's performance has been optimized
      during growth with glucose. However, lignocellulosic biomass hydrolysates also
      contain a substantial portion of hemicellulose-derived xylose, which is typically
      the second most abundant sugar after glucose. Commercialization of the methyl
      ketone-producing technology would benefit from the increased efficiency resulting
      from simultaneous, rather than the native sequential (diauxic), utilization of
      glucose and xylose. RESULTS: In this study, genetic manipulations were performed
      to alleviate carbon catabolite repression in our most efficient methyl ketone
      producing strain. A strain engineered for constitutive expression of xylF and
      xylA (involved in xylose transport and metabolism) showed synchronized glucose
      and xylose consumption rates. However, this newly acquired capability came at the
      expense of methyl ketone titer, which decreased fivefold. Further efforts were
      made to improve methyl ketone production in this strain, and we found that two
      strategies were effective at enhancing methyl ketone titer: (1) chromosomal
      deletion of pgi (glucose-6-phosphate isomerase) to increase intracellular NADPH
      supply and (2) downregulation of CRP (cAMP receptor protein) expression by
      replacement of the native RBS with an RBS chosen based upon mutant library
      screening results. Combining these strategies resulted in the most favorable
      overall phenotypes for simultaneous glucose-xylose consumption without
      compromising methyl ketone titer at both 1 and 2% total sugar concentrations in
      shake flasks. CONCLUSIONS: This work demonstrated a strategy for engineering
      simultaneous utilization of C6 and C5 sugars in E. coli without sacrificing
      production of fatty acid-derived compounds.

PMID- 29374484
TI  - Distant and proximate factors associated with maternal near-miss: a nested case
      control study in selected public hospitals of Addis Ababa, Ethiopia.
AB  - BACKGROUND: Ethiopia is one of the sub-Saharan Africa countries with the highest
      maternal mortality. Maternal near-misses are more common than deaths and
      statistically stronger for a comprehensive analysis of the determinants. The
      study aimed to identify the factors associated with maternal near-miss in
      selected public hospitals of Addis Ababa, Ethiopia. METHODS: We conducted a
      nested case-control study in five selected public hospitals of Addis Ababa,
      Ethiopia from May 1, 2015 to April 30, 2016. Participants were interviewed by
      well-trained data collectors using pre-tested questionnaire. Medical records were
      also reviewed to gather relevant information. World Health Organization criteria
      were used to identify maternal near-miss cases. A total of three controls matched
      for age and study area was selected for each maternal near-miss case. Bivariate
      and multivariable conditional logistic regressions were performed using Stata
      version 13.0. RESULTS: A total of 216 maternal near-miss cases and 648 controls
      were included in the study. The main factors associated with maternal near-miss
      were: history of chronic hypertension (AOR = 10.80,95% CI; 5.16-22.60), rural
      residency (AOR = 10.60,95% CI;4.59-24.46), history of stillbirth (AOR = 6.03,95%
      CI;2.09-17.41), no antenatal care attendance (AOR = 5.58,95% CI;1.94-16.07) and
      history of anemia (AOR = 5.26,95% CI;2.89-9.57). CONCLUSIONS: There is a need for
      appropriate interventions in order to improve the identified factors. The factors
      can be modified through a better access to medical and maternity care, scaling up
      of antenatal care in rural areas, improve in infrastructure to fulfill referral
      chain from primary level to secondary and tertiary health care levels, and health
      education to pregnant women.

PMID- 29374485
TI  - Fake facts and alternative truths in medical research.
AB  - BACKGROUND: Fake news and alternative facts have become commonplace in these so
      called "post-factual times." What about medical research - are scientific facts
      fake as well? Many recent disclosures have fueled the claim that scientific facts
      are suspect and that science is in crisis. Scientists appear to engage in facting
      interests instead of revealing interesting facts. This can be observed in terms
      of what has been called polarised research, where some researchers continuously
      publish positive results while others publish negative results on the same issue 
      even when based on the same data. In order to identify and address this
      challenge, the objective of this study is to investigate how polarised research
      produce "polarised facts." Mammography screening for breast cancer is applied as
      an example. MAIN BODY: The main benefit with mammography screening is the reduced
      breast cancer mortality, while the main harm is overdiagnosis and subsequent
      overtreatment. Accordingly, the Overdiagnosis to Mortality Reduction Ratio (OMRR)
      is an estimate of the risk-benefit-ratio for mammography screening. As there are
      intense interests involved as well as strong opinions in debates on mammography
      screening, one could expect polarisation in published results on OMRR. A
      literature search identifies 8 studies publishing results for OMRR and reveals
      that OMRR varies 25-fold, from 0.4 to 10. Two experts in polarised research were
      asked to rank the attitudes of the corresponding authors to mammography screening
      of the identified publications. The results show a strong correlation between the
      OMRR and the authors' attitudes to screening (R = 0.9). CONCLUSION: Mammography
      screening for breast cancer appears as an exemplary field of strongly polarised
      research. This is but one example of how scientists' strong professional
      interests can polarise research. Instead of revealing interesting facts
      researchers may come to fact interests. In order to avoid this and sustain trust
      in science, researchers should disclose professional and not only financial
      interests when submitting and publishing research.

PMID- 29374486
TI  - Quality of care during childbirth in Tanzania: identification of areas that need
      improvement.
AB  - BACKGROUND: Making use of good, evidence based routines, for management of normal
      childbirth is essential to ensure quality of care and prevent, identify and
      manage complications if they occur. Two essential routine care interventions as
      defined by the World Health Organization are the use of the Partograph and Active
      Management of the Third Stage of Labour. Both interventions have been evaluated
      for their ability to assist health providers to detect and deal with
      complications. There is however little research about the quality of such
      interventions for routine care. Qualitative studies can help to understand how
      such complex interventions are implemented. This paper reports on findings from
      an observation study on maternity wards in Tanzania. METHODS: The study took
      place in the Lake Zone in Tanzania. Between 2014 and 2016 the first author
      observed and participated in the care for women on maternity wards in four rural
      and semi-urban health facilities. The data is a result of approximately 1300
      hours of observations, systematically recorded primarily in observation notes and
      notes of informal conversations with health providers, women and their families.
      Detailed description of care processes were analysed using an ethnographic
      analysis approach focused on the sequential relationship of the 'stages of
      labour'. Themes were identified through identification of recurrent patterns.
      RESULTS: Three themes were identified: 1) Women's movement between rooms during
      birth, 2) health providers' assumptions and hope for a 'normal' birth, 3) fear of
      poor outcomes that stimulates intervention during birth. Women move between
      different rooms during childbirth which influences the care they receive. Few
      women were monitored during their first stage of labour. Routine birth monitoring
      appeared absent due to health providers 'assumptions and hope for good outcomes.
      This was rooted in a general belief that most women eventually give birth without
      problems and the partograph did not correspond with health providers' experience
      of the birth process. Contextual circumstances also limited health worker ability
      to act in case of complications. At the same time, fear for being held personally
      responsible for outcomes triggered active intervention in second stage of labour,
      even if there was no indication to intervene. CONCLUSIONS: Insufficient
      monitoring leads to poor preparedness of health providers both for normal birth
      and in case of complications. As a result both underuse and overuse of
      interventions contribute to poor quality of care. Risk and complication
      management have for many years been prioritized at the expense of routine care
      for all women. Complex evaluations are needed to understand the current
      implementation gaps and find ways for improving quality of care for all women.

PMID- 29374487
TI  - Current trials for frontline therapy of mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a rare and incurable subtype of non-Hodgkin's
      lymphoma that generally affects older individuals. However, the use of high-dose
      therapy and autologous stem cell transplant has improved significantly the
      prognosis of this hematological malignancy, but at the cost of increased
      toxicities, such as acute toxic death and secondary malignancies. But thanks to a
      rising understanding of the biology of MCL, the explosion of specifically
      targeted new efficacious agents, immunotherapy agents, and cellular therapies in
      the frontline setting, the prognosis of MCL is expected to improve
      dramatically.The initial treatment of MCL is currently not standardized and the
      therapeutic landscape of MCL is rapidly evolving. This review provides an
      extensive overview of the current frontline therapy trials for MCL and presents
      the results of innovative regimen, including some integrating novel agents and
      desintensified chemotherapy.

PMID- 29374488
TI  - Effects of dance on cognitive function among older adults: a protocol for
      systematic review and meta-analysis.
AB  - BACKGROUND: Cognitive impairment is characterized by problems in thinking,
      memory, language, and judgment that are greater than cognitive changes in normal
      aging. Considering the unprecedented growth of the older adult population and the
      projected increase in the prevalence of cognitive impairment, it is imperative to
      find effective strategies to improve or maintain cognitive function in older
      adults. The objective of this review is to summarize the effects of dance versus
      any other control group on cognitive function, physical function, adverse events,
      and quality of life in older adults. METHOD: We will search the following
      databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials
      (CENTRAL) to identify the randomized controlled trials (RCTs) evaluating the
      effects of dance on cognitive function among older adults. Also, we will search
      http://apps.who.int/trialsearch , clinicaltrials.gov and conference abstracts to
      identify ongoing and unpublished studies. There will be no restrictions on
      language, date, or journal of publication. Reviewers will independently and in
      duplicate screen for eligible studies using pre-defined criteria. Data extraction
      from eligible studies will be performed independently and in duplicate. The
      Cochrane risk of bias tool will be used to assess the risk of bias of studies.
      Our primary outcome of interest is cognitive function, more specifically the
      executive function domain. We will include other domains as well such as
      processing speed and reaction time. Secondary outcomes of interest are physical
      function. The secondary outcomes also include adverse events including falls and
      quality of life. We will use Review Manager (RevMan 5.3) to pool the effect of
      dance for each outcome where possible. Results will be presented as relative
      risks along with 95% confidence intervals for dichotomous outcomes and as mean
      differences, or standardized mean differences along with 95% confidence
      intervals, for continuous outcomes. We will assess the certainty of the evidence
      using the GRADE approach and present findings in a Summary of Findings table.
      DISCUSSION: This systematic review, to our best knowledge the first-ever, will
      synthesize the available evidence on the effects of dance on cognitive function
      among older people. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017057138.

PMID- 29374489
TI  - Stress ulcer prophylaxis in intensive care unit patients receiving enteral
      nutrition: a systematic review and meta-analysis.
AB  - BACKGROUND: Pharmacologic stress ulcer prophylaxis (SUP) is recommended in
      critically ill patients with high risk of stress-related gastrointestinal (GI)
      bleeding. However, as to patients receiving enteral feeding, the preventive
      effect of SUP is not well-known. Therefore, we performed a meta-analysis of
      randomized controlled trials (RCTs) to evaluate the effect of pharmacologic SUP
      in enterally fed patients on stress-related GI bleeding and other clinical
      outcomes. METHODS: We searched PubMed, Embase, and the Cochrane database from
      inception through 30 Sep 2017. Eligible trials were RCTs comparing pharmacologic
      SUP to either placebo or no prophylaxis in enterally fed patients in the ICU.
      Results were expressed as risk ratio (RR) and mean difference (MD) with
      accompanying 95% confidence interval (CI). Heterogeneity, subgroup analysis,
      sensitivity analysis and publication bias were explored. RESULTS: Seven studies
      (n = 889 patients) were included. There was no statistically significant
      difference in GI bleeding (RR 0.80; 95% CI, 0.49 to 1.31, p = 0.37) between
      groups. This finding was confirmed by further subgroup analyses and sensitivity
      analysis. In addition, SUP had no effect on overall mortality (RR 1.21; 95% CI,
      0.94 to 1.56, p = 0.14), Clostridium difficile infection (RR 0.89; 95% CI, 0.25
      to 3.19, p = 0.86), length of stay in the ICU (MD 0.04 days; 95% CI, -0.79 to
      0.87, p = 0.92), duration of mechanical ventilation (MD -0.38 days; 95% CI, -1.48
      to 0.72, p = 0.50), but was associated with an increased risk of hospital
      acquired pneumonia (RR 1.53; 95% CI, 1.04 to 2.27; p = 0.03). CONCLUSIONS: Our
      results suggested that in patients receiving enteral feeding, pharmacologic SUP
      is not beneficial and combined interventions may even increase the risk of
      nosocomial pneumonia.

PMID- 29374490
TI  - Apple endophytic microbiota of different rootstock/scion combinations suggests a
      genotype-specific influence.
AB  - BACKGROUND: High-throughput amplicon sequencing spanning conserved portions of
      microbial genomes (16s rRNA and ITS) was used in the present study to describe
      the endophytic microbiota associated with three apple varieties, "Royal Gala,"
      "Golden Delicious," and "Honey Crisp," and two rootstocks, M.9 and M.M.111. The
      objectives were to (1) determine if the microbiota differs in different
      rootstocks and apple varieties and (2) determine if specific rootstock-scion
      combinations influence the microbiota composition of either component. RESULTS:
      Results indicated that Ascomycota (47.8%), Zygomycota (31.1%), and Basidiomycota
      (11.6%) were the dominant fungal phyla across all samples. The majority of
      bacterial sequences were assigned to Proteobacteria (58.4%), Firmicutes (23.8%),
      Actinobacteria (7.7%), Bacteroidetes (2%), and Fusobacteria (0.4%). Rootstocks
      appeared to influence the microbiota of associated grafted scion, but the effect
      was not statistically significant. Pedigree also had an impact on the composition
      of the endophytic microbiota, where closely-related cultivars had a microbial
      community that was more similar to each other than it was to a scion cultivar
      that was more distantly-related by pedigree. The more vigorous rootstock
      (M.M.111) was observed to possess a greater number of growth-promoting bacterial
      taxa, relative to the dwarfing rootstock (M.9). CONCLUSIONS: The mechanism by
      which an apple genotype, either rootstock or scion, has a determinant effect on
      the composition of a microbial community is not known. The similarity of the
      microbiota in samples with a similar pedigree suggests the possibility of some
      level of co-evolution or selection as proposed by the "holobiont" concept in
      which metaorganisms have co-evolved. Clearly, however, the present information is
      only suggestive, and a more comprehensive analysis is needed.

PMID- 29374491
TI  - Prosthetic energy return during walking increases after 3 weeks of adaptation to
      a new device.
AB  - BACKGROUND: There are many studies that have investigated biomechanical
      differences among prosthetic feet, but not changes due to adaptation over time.
      There is a need for objective measures to quantify the process of adaptation for
      individuals with a transtibial amputation. Mechanical power and work profiles are
      a primary focus for modern energy-storage-and-return type prostheses, which
      strive to increase energy return from the prosthesis. The amount of energy a
      prosthesis stores and returns (i.e., negative and positive work) during stance is
      directly influenced by the user's loading strategy, which may be sensitive to
      alterations during the course of an adaptation period. The purpose of this study
      was to examine changes in lower limb mechanical work profiles during walking
      following a three-week adaptation to a new prosthesis. METHODS: A retrospective
      analysis was performed on 22 individuals with a unilateral transtibial
      amputation. Individuals were given a new prosthesis at their current mobility
      level (K3 or above) and wore it for three weeks. Kinematic and kinetic measures
      were recorded from overground walking at 0, 1.5, and 3 weeks into the adaptation
      period at a self-selected pace. Positive and negative work done by the prosthesis
      and sound ankle-foot were calculated using a unified deformable segment model and
      a six-degrees-of-freedom model for the knee and hip. RESULTS: Positive work from
      the prosthesis ankle-foot increased by 6.1% and sound ankle-foot by 5.7% after 3
      weeks (p = 0.041, 0.036). No significant changes were seen in negative work from
      prosthesis or sound ankle-foot (p = 0.115, 0.192). There was also a 4.1% increase
      in self-selected walking speed after 3 weeks (p = 0.038). Our data exhibited
      large inter-subject variations, in which some individuals followed group trends
      in work profiles while others had opposite trends in outcome variables.
      CONCLUSIONS: After a 3-week adaptation, 14 out of 22 individuals with a
      transtibial amputation increased energy return from the prosthesis. Such findings
      could indicate that individuals may better utilize the spring-like function of
      the prosthesis after an adaptation period.

PMID- 29374492
TI  - Prediction of opioid dose in cancer pain patients using genetic profiling: not
      yet an option with support vector machine learning.
AB  - OBJECTIVE: Use of opioids for pain management has increased over the past decade;
      however, inadequate analgesic response is common. Genetic variability may be
      related to opioid efficacy, but due to the many possible combinations and
      variables, statistical computations may be difficult. This study investigated
      whether data processing with support vector machine learning could predict
      required opioid dose in cancer pain patients, using genetic profiling. Eighteen
      single nucleotide polymorphisms (SNPs) within the u and delta opioid receptor
      genes and the catechol-O-methyltransferase gene were selected for analysis.
      RESULTS: Data from 1237 cancer pain patients were included in the analysis.
      Support vector machine learning did not find any associations between the
      assessed SNPs and opioid dose in cancer pain patients, and hence, did not provide
      additional information regarding prediction of required opioid dose using genetic
      profiling.

PMID- 29374493
TI  - Over-expression of oncigenic pesudogene DUXAP10 promotes cell proliferation and
      invasion by regulating LATS1 and beta-catenin in gastric cancer.
AB  - BACKGROUND: Recently, the pesudogenes have emerged as critical regulators in
      human cancers tumorigenesis and progression, and been identified as a key
      revelation in post-genomic biology. However, the expression pattern, biological
      function and mechanisms responsible for these molecules in human gastric cancer
      (GC) are not fully understood. METHODS: In this study, we globally assessed the
      transcriptomic differences of pesudogenes in gastric cancer using publicly
      available microarray data. DUXAP10 expression levels in GC tissues and cells was
      detected using quantitative real-time PCR (qPCR). DUXAP10 siRNAs and over
      expression vector were transfected into GC cells to down-regulate or up-regulate
      DUXAP10 expression. Loss- and gain-of function assays were performed to
      investigate the role of DUXAP10 in GC cells cell proliferation, and invasion.
      RIP, RNA pulldown, and ChIP assays were used to determine the mechanism of
      DUXAP10's regulation of underlying targets. RESULTS: The pesudogene DUXAP10 is
      the only pseudogene that significantly over-expressed in all four GEO datasets,
      and frequently over-expressed in many other cancers including Liver
      Hepatocellular carcinoma, Bladder cancer, and Esophageal Cancer. High DUXAP10
      expression is associated with GC patients poor prognosis, and knockdown of
      DUXAP10 significantly inhibits cells proliferation, migration and invasion in GC.
      Mechanistic investigation shows that DUXAP10 can interact with PRC2 and LSD1 to
      repress LATS1 expression at transcriptional level, and bind with HuR to maintain
      the stability of beta-catenin mRNA and increase its protein levels at post
      transcriptional level. CONCLUSIONS: Overall, our findings illuminate how
      increased DUXAP10 confers an oncogenic function in GC development and progression
      that may serve as a candidate prognostic biomarker and target for clinical
      management of GC.

PMID- 29374494
TI  - Inconsistencies in the drawing and interpretation of smiley faces: an
      observational study.
AB  - OBJECTIVES: Pre-prepared smiley face symbols are used widely to gather
      information on, for example, satisfaction with services or health and well-being.
      We investigated how women and men of different ages respond when asked to draw a
      smiley face for themselves. Our objectives were to investigate how they differ by
      generating a unique set of data to explore this simple human behaviour and to
      illustrate the importance of considering gender and age mix in any study.
      RESULTS: We collected 723 drawings, in a variety of settings. Gender and age were
      provided for 676 drawings (women: 511; men: 165; <= 30 years: 335; > 30 years:
      341). Although similar proportions of women and men drew some features, such as
      closed mouths; women and those aged <= 30 were less likely to draw noses and
      outlines around the faces, and more likely to draw a classic smiley face. Our
      analyses provide a novel way to highlight that whenever self-reported outcomes
      are compared between groups, the group composition for characteristics such as
      gender and age may need to be considered carefully to explore whether differences
      in outcomes might simply arise from imbalances in those characteristics.

PMID- 29374495
TI  - Long term substrate reduction therapy with ezetimibe alone or associated with
      statins in three adult patients with lysosomal acid lipase deficiency.
AB  - BACKGROUND: Lysosomal acid lipase deficiency is an autosomal recessive metabolic
      disease with a wide range of severity from Wolman Disease to Cholesterol Ester
      Storage Disease. Recently enzyme replacement therapy with sebelipase alpha has
      been approved by drug agencies for treatment of this lysosomal disease. Ezetimibe
      is an azetidine derivative which blocks Niemann Pick C1-Like 1 Protein; as its
      consequence, plasmatic concentration of low density lipoproteins and other apoB
      containing lipoproteins, that are the substrate of lysosomal acid lipase, are
      decreased. Furthermore, ezetimibe acts by blocking inflammasome activation which
      is the cause of liver fibrosis in steatohepatitis and in lysosomal storage
      diseases. RESULTS: Two patients with Cholesterol Ester Storage Disease were
      treated with ezetimibe for 9 years and a third patients for 10 years. Treatment
      was supplemented with low dose of atorvastatin in the first two patients during
      the last 6 years. All patients showed a significant reduction of alanine
      aminotransferase, cholesterol and triglyceride. Furthermore, no progression of
      liver fibrosis was demonstrated. CONCLUSION: In this observational case series,
      ezetimibe is effective, safe, and sustainable treatment for lysosomal acid lipase
      deficiency. Further studies are warranted to demonstrate that ezetimibe is an
      alternative therapy to enzyme replacement therapy.

PMID- 29374496
TI  - Metagenomic investigation of vestimentiferan tubeworm endosymbionts from Mid
      Cayman Rise reveals new insights into metabolism and diversity.
AB  - BACKGROUND: The microbial endosymbionts of two species of vestimentiferan
      tubeworms (Escarpia sp. and Lamellibrachia sp.2) collected from an area of low
      temperature hydrothermal diffuse vent flow at the Mid-Cayman Rise (MCR) in the
      Caribbean Sea were characterized using microscopy, phylogenetic analyses, and a
      metagenomic approach. RESULTS: Bacteria, with a typical Gram negative cell
      envelope contained within membrane-bound vacuoles, were observed within the
      trophosome of both tubeworm species. Phylogenetic analysis of the 16S rRNA gene
      and ITS region suggested MCR individuals harbored highly similar endosymbionts
      that were > 98% identical, with the exception of two symbionts that showed a 60
      bp insertion within the ITS region. All sequences from MCR endosymbionts formed a
      separate well-supported clade that diverged from those of symbionts of seep and
      vent vestimentiferans from the Pacific, Gulf of Mexico, and Mediterranean Sea.
      The metagenomes of the symbionts of two specimens of each tubeworm species were
      sequenced, and two distinct Gammaproteobacteria metagenome-assembled genomes
      (MAGs) of more than 4 Mbp assembled. An Average Nucleotide Identity (ANI) of
      86.5% between these MAGs, together with distinct 16S rRNA gene and ITS sequences,
      indicate the presence of multiple endosymbiont phylotypes at the MCR, with one
      MAG shared between one Escarpia and two Lamellibrachia individuals, indicating
      these endosymbionts are not specific to either host species. Genes for sulfur and
      hydrogen oxidation, nitrate reduction (assimilatory and dissimilatory),
      glycolysis and the Krebs cycle, peptide, sugar, and lipid transporters, and both
      rTCA and CBB carbon fixation cycles were detected in the MAGs, highlighting key
      and shared functions with symbiont metagenomes of the vestimentiferans Riftia,
      Tevnia, and Ridgeia from the Pacific. The potential for a second hydrogen
      oxidation pathway (via a bidirectional hydrogenase), formate dehydrogenase, a
      catalase, and several additional peptide transporters were found exclusively in
      the MCR endosymbiont MAGs. CONCLUSIONS: The present study adds new evidence that
      tubeworm endosymbionts can potentially switch from autotrophic to heterotrophic
      metabolism, or may be mixotrophic, presumably while free-living, and also
      suggests their versatile metabolic potential may enable both the host and
      symbionts to exploit a wide range of environmental conditions. Together, the
      marked gene content and sequence dissimilarity at the rRNA operon and whole
      genome level between vent and seep symbionts suggest these newly described
      endosymbionts from the MCR belong to a novel tubeworm endosymbiont genera,
      introduced as Candidatus Vondammii.

PMID- 29374497
TI  - Implementing measurement based care in community mental health: a description of
      tailored and standardized methods.
AB  - OBJECTIVE: Although tailored implementation methods are touted as superior to
      standardized, few researchers have directly compared the two and little guidance
      regarding the specific details of each method exist. Our study compares these
      methods in a dynamic cluster randomized trial seeking to optimize implementation
      of measurement based care (MBC) for depression in community behavioral health.
      This specific manuscript provides a detailed, replicable account of the
      components of each multi-faceted implementation method. RESULTS: The standardized
      best practice method includes training, consultation, a clinical guideline, and
      electronic health record enhancements with the goal to optimize the delivery of
      MBC with fidelity. Conversely, the tailored, customized and collaborative method
      is informed by recent implementation science advancements and begins with a needs
      assessment, followed by tailored training that feeds back barriers data to
      clinicians, the formation of an implementation team, a clinician-driven clinic
      specific guideline, and the use of fidelity data to inform implementation team
      activities; the goal of the tailored condition is to ensure the intervention and
      implementation strategies address unique factors of the context. The description
      of these methods will inform others seeking to implement MBC, as well as those
      planning to use standardized or tailored implementation methods for interventions
      beyond behavioral health.

PMID- 29374499
TI  - Long-term efficacy of standardised specific subcutaneous immunotherapy in
      children with persistent allergic rhinitis due to multiple allergens including
      house dust mites.
AB  - OBJECTIVES: To observe the five-year efficacy of standardised specific
      subcutaneous immunotherapy for house dust mite allergy in monosensitised and
      polysensitised children with persistent allergic rhinitis. METHODS: From January
      2007 to August 2009, 236 children with persistent allergic rhinitis were divided
      into 2 groups: 1 group received standardised specific subcutaneous immunotherapy
      using house dust mite extract; the other received pharmacotherapy with intranasal
      corticosteroids and oral antihistamines. A total of 193 patients (106 in the
      immunotherapy group and 87 in the pharmacotherapy group) completed treatment.
      Scores for symptoms, total medication and quality of life were evaluated.
      RESULTS: The subcutaneous immunotherapy group demonstrated a significant
      reduction in visual analogue scale scores, Rhinoconjunctivitis Quality of Life
      Questionnaire scores and total medication scores (p 0.05). No serious adverse
      events occurred. CONCLUSION: Standardised subcutaneous immunotherapy has long
      term efficacy for children with persistent allergic rhinitis. Single-allergen
      subcutaneous immunotherapy was appropriate for allergic rhinitis caused by
      multiple allergens, including house dust mites, in the paediatric population.

PMID- 29374500
TI  - Headache and Papilledema in Guillain-Barre Syndrome.

PMID- 29374498
TI  - Transfers from intensive care unit to hospital ward: a multicentre textual
      analysis of physician progress notes.
AB  - BACKGROUND: Little is known about documentation during transitions of patient
      care between clinical specialties. Therefore, we examined the focus, structure
      and purpose of physician progress notes for patients transferred from the
      intensive care unit (ICU) to hospital ward to identify opportunities to improve
      communication breaks. METHODS: This was a prospective cohort study in ten
      Canadian hospitals. We analyzed physician progress notes for consenting adult
      patients transferred from a medical-surgical ICU to hospital ward. The number,
      length, legibility and content of notes was counted and compared across care
      settings using mixed-effects linear regression models accounting for clustering
      within hospitals. Qualitative content analyses were conducted on a stratified
      random sample of 32 patients. RESULTS: A total of 447 patient medical records
      that included 7052 progress notes (mean 2.1 notes/patient/day 95% CI 1.9-2.3)
      were analyzed. Notes written by the ICU team were significantly longer than notes
      written by the ward team (mean lines of text 21 vs. 15, p < 0.001). There was a
      discrepancy between documentation of patient issues in the last ICU and first
      ward notes; mean agreement of patient issues was 42% [95% CI 31-53%]. Qualitative
      analyses identified eight themes related to focus (central point - e.g., problem
      list), structure (organization, - e.g., note-taking style), and purpose
      (intention - e.g., documentation of patient course) of the notes that varied
      across clinical specialties and physician seniority. CONCLUSIONS: Important gaps
      and variations in written documentation during transitions of patient care
      between ICU and hospital ward physicians are common, and include discrepancies in
      documentation of patient information.

PMID- 29374501
TI  - Pulmonary Embolism in Ischemic Stroke.
AB  - Silent pulmonary embolism (PE) may be associated with acute ischemic stroke
      (AIS). We identified 10 patients from 3,132 unique patients (3,431 CT scans). We
      retrospectively examined CT angiogram of patients with AIS to determine the
      frequency of concurrent PE in AIS. The period prevalence of PE was 0.32. Seven
      patients had concurrent PE, whereas three had PE diagnosed 2 days after their AIS
      presentation. We suspected paradoxical embolism via patent foramen ovale as the
      cause of stroke in three patients and thrombophilia in four patients. Seven
      patients had poor outcome including four deaths. CT angiogram stroke protocol
      images from aortic arch to vertex allows visualization of upper pulmonary
      arteries and PE detection in AIS.

PMID- 29374502
TI  - Changes in renal hemodynamics of undernourished fetuses appear earlier than IUGR
      evidences.
AB  - The present study used a sheep model of intrauterine growth restriction,
      combining maternal undernutrition and twinning, to determine possible markers of
      early damage to the fetal kidney. The occurrence of early deviations in fetal
      hemodynamics which may be indicative of changes in blood perfusion was assessed
      by Doppler ultrasonography. A total of 24 sheep divided in two groups were fed
      with the same standard grain-based diet but fulfilling either their daily
      maintenance requirements for pregnancy (control group; n=12, six singleton and
      six twin pregnancies) or only the 50% of such quantity (food-restricted group;
      n=12; four singleton and eight twin pregnancies). All the fetuses were assessed
      by both B-mode and Doppler ultrasonography at Day 115 of pregnancy. Fetal blood
      supply was affected by maternal undernutrition, although there were still no
      evidences of brain-sparing excepting in fetuses at greatest challenge (twins in
      underfed pregnancies). However, there were early changes in the blood supply to
      the kidneys of underfed fetuses and underfed twins evidenced decreases in kidney
      size.

PMID- 29374503
TI  - Alcohols as Surface Disinfectants in Healthcare Settings.
AB  - Isopropyl alcohol and ethyl alcohol have been used as low-level disinfectants in
      healthcare settings for many years. Recent studies have found that ethyl alcohol
      inhibits protein synthesis in Escherichia coli by direct effects on ribosomes and
      RNA polymerase and that 60%-70% solutions have in vitro efficacy against murine
      norovirus, Ebola virus, and several coronaviruses. Alcohol prep pads or
      towelettes containing isopropyl or ethyl alcohol and water have been used
      primarily for disinfection of small noncritical items due to a concern regarding
      their rapid evaporation rates and associated short contact times. Sterile alcohol
      solutions are used mostly for disinfection of compounding pharmacies and
      controlled areas. One new Environmental Protection Agency (EPA)-registered
      cleaner/disinfectant formulation differs from other alcohol-based disinfectants
      by virtue of having a 30-second contact time for multiple pathogens and a
      toxicity rating of category IV. Multiple disinfectants containing ethyl alcohol
      and/or isopropyl alcohol combined with other active agents such as quaternary
      ammonium or phenolic compounds are widely used for disinfecting environmental
      surfaces in healthcare facilities. Infect Control Hosp Epidemiol 2018;39:323-328.

PMID- 29374504
TI  - The Role of Negative Methicillin-Resistant Staphylococcus aureus Nasal
      Surveillance Swabs in Predicting the Need for Empiric Vancomycin Therapy in
      Intensive Care Unit Patients.
AB  - OBJECTIVES The role of methicillin-resistant Staphylococcus aureus (MRSA) nasal
      surveillance swabs (nasal swabs) in guiding decisions about prescribing
      vancomycin is unclear. We aimed to determine the likelihood that patients with
      negative MRSA nasal swabs develop subsequent MRSA infections; to assess avoidable
      vancomycin days for patients with negative nasal swabs; and to identify risk
      factors for having a negative nasal swab and developing a MRSA infection during
      the intensive care unit (ICU) stay. METHODS This retrospective cohort study was
      conducted in 6 ICUs at a tertiary-care hospital from December 2013 through June
      2015. The negative predictive value (NPV), defined as the ability of a negative
      nasal swab to predict no subsequent MRSA infection, was calculated. Days of
      vancomycin continued or restarted after 3 days from the collection time of the
      first negative nasal swab were determined. A matched case-control study
      identified risk factors for having a negative nasal swab and developing MRSA
      infection. RESULTS Of 11,441 patients with MRSA-negative nasal swabs, the rate of
      subsequent MRSA infection was 0.22%. A negative nasal swab had a NPV of 99.4%
      (95% confidence interval [CI], 99.1%-99.6%). Vancomycin was continued or started
      after nasal swab results were available in 1,431 patients, translating to 7,364
      vancomycin days. No risk factors associated with MRSA infection were identified.
      CONCLUSIONS In our hospital with a low prevalence of MRSA transmission, a
      negative MRSA nasal swab was helpful in identifying patients with low risk of
      MRSA infection in whom empiric vancomycin therapy could be stopped and in whom
      the subsequent initiation of vancomycin therapy during an ICU admission could be
      avoided. Infect Control Hosp Epidemiol 2018;39:290-296.

PMID- 29374505
TI  - An environmental scan of academic pediatric emergency medicine at Canadian
      medical schools: Identifying variability across Canada.
AB  - OBJECTIVE: To complement our environmental scan of academic emergency medicine
      departments, we conducted a similar environmental scan of the academic pediatric
      emergency medicine programs offered by the Canadian medical schools. METHODS: We
      developed an 88-question form, which was distributed to pediatric academic
      leaders at each medical school. The responses were validated via email to ensure
      that the questions were answered completely and consistently. RESULTS: Fourteen
      of the 17 Canadian medical schools have some type of pediatric emergency medicine
      academic program. None of the pediatric emergency medicine units have full
      departmental status, while nine are divisions, two are sections, and three have
      no status. Canadian academic pediatric emergency medicine is practised at 13
      major teaching hospitals and one specialized pediatric emergency department.
      There are 394 pediatric emergency medicine faculty members, including 13 full
      professors and 64 associate professors. Eight sites regularly take pediatric
      undergraduate clinical clerks, and all 14 provide resident education. Fellowship
      training is offered at 10 sites, with five offering advanced pediatric emergency
      medicine fellowship training. Half of the sites have at least one physician with
      a Master's degree in education, totalling 18 faculty members across Canada. There
      are 31 clinical researchers with salary support at nine universities. Eleven
      sites have published peer-reviewed papers (n=423) in the past five years, ranging
      from two to 102 per site. Annual academic budgets range from $10,000 to
      $2,607,515. CONCLUSIONS: This comprehensive review of academic activities in
      pediatric emergency medicine across Canada identifies the variability across the
      country, including the recognition of sites above and below the national average,
      which may prompt change at individual sites. Sharing these academic practices may
      inspire sites to provide more support to teachers, educators, and researchers.

PMID- 29374506
TI  - Nepal's Health Facility Operation and Management Committees: exploring community
      participation and influence in the Dang district's primary care clinics.
AB  - : AimTo describe community representation in Nepal's Health Facility Operation
      and Management Committees (HFMCs) and the degree of influence of community
      representatives in the HFMC decision-making processes. BACKGROUND: Community
      participation has been recognised as one of the key components for the successful
      implementation of primary health care (PHC) strategies, following the 1978
      Declaration of Alma-Ata. In low- and middle-income countries (LMICs), HFMCs are
      now widely considered as a mechanism to increase community participation in
      health through community representation. There is some research examining the
      implementation process, impact and factors affecting the effectiveness of HFMCs.
      Despite the documented evidence of the importance of factors such as adequate
      representation, links with wider community, and decision-making power, there is
      limited evidence about the nature of community representation and degree of
      decision making within HFMCs in the PHC setting, particularly in LMICs. METHODS:
      Qualitative interviews with 39 key informants were held to explore different
      aspects of community representation in HFMCs, and the influence of the HFMC on
      health facility decision-making processes. In addition, a facility audit at 22
      facilities and review of HFMC meeting minutes at six health facilities were
      conducted.FindingsThere were Dalit (a marginalised caste) and Janajati (an ethnic
      group) representations in 77% and 100% of the committees, respectively. Likewise,
      there were at least two female members in each committee. However, the HFMC
      member selection process and decision making within the committees were
      influenced by powerful elites. The degree of participation through HFMCs appeared
      to be at the 'Manipulation' and 'Informing' stage of Arnstein's ladder of
      participation. In conclusion, despite representation of the community on HFMCs,
      the depth of participation seems low. There is a need to ensure a democratic
      selection process of committee members; and to expand the depth of participation.

PMID- 29374507
TI  - EBI2 regulates pro-inflammatory signalling and cytokine release in astrocytes.
AB  - The endogenous oxysterol 7alpha, 25-dihydroxycholesterol (7alpha25HC) ligand
      activates the G protein-coupled receptor EBI2 to regulate T cell-dependant
      antibody response and B cell migration. We have demonstrated that EBI2 is
      expressed in human and mouse astrocytes, that 7alpha25HC induces intracellular
      signalling and astrocyte migration, and that EBI2 plays a role in the crosstalk
      between astrocytes and macrophages. Recently, we demonstrate that EBI2 regulates
      myelin development and inhibits LPC-induced demyelination. Here, we show that
      7alpha25HC inhibits LPS- and IL17/TNF-induced pro-inflammatory cytokine release
      in astrocytes. We observe the following: 1. Human astrocytes treated with
      IL17/TNF increases the nuclear translocation of NFkappaB, which is attenuated by
      pre-treatment with 7alpha25HC; 2. IL17/TNF increases cell impedance in human
      astrocytes, which is also attenuated by pre-treatment with 7alpha25HC; 3. The
      EBI2 antagonist NIBR189 inhibits these effects of 7alpha25HC, supporting the role
      of EBI2; 4. in vivo data corroborate these in vitro findings, showing that EBI2
      knock-out (KO) animals display enhanced pro-inflammatory cytokine in response to
      LPS challenge, in the brain. These results demonstrate a role for oxysterol/EBI2
      signalling in attenuating the response of astrocytes to pro-inflammatory signals
      as well as limiting the levels of pro-inflammatory cytokines in the brain.

PMID- 29374508
TI  - Re-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic
      applications.
AB  - A key challenge in the development of novel chemotherapeutics is the design of
      molecules capable of selective toxicity to cancer cells. Antibodies have greater
      target specificity compared to small molecule drugs, but most are unable to
      penetrate cells, and predominantly target extracellular antigens. A nuclear
      penetrating anti-DNA autoantibody isolated from the MRL/lpr lupus mouse model,
      3E10, preferentially localizes to tumors, inhibits DNA repair, and selectively
      kills cancer cells with defects in DNA repair. A murine divalent single chain
      variable fragment of 3E10 with mutations for improved DNA binding affinity, 3E10
      (D31N) di-scFv, has previously been produced in P. pastoris and yielded promising
      pre-clinical findings, but is unsuitable for clinical testing. The present study
      reports the design, expression and testing of a panel of humanized 3E10 (D31N) di
      scFvs, some of which contain CDR substitution. These variants were expressed in a
      modified CHO system and evaluated for their physicochemical attributes and
      ability to penetrate nuclei to selectively cause DNA damage accumulation in and
      kill cancer cells with DNA repair defects. Secondary structure was conserved and
      most variants retained the key characteristics of the murine 3E10 (D31N) di-scFv
      produced in P. pastoris. Moreover, several variants with CDR substitutions
      outperformed the murine prototype. In conclusion, we have designed several
      humanized variants of 3E10 (D31N) di-scFv that have potential for application as
      monotherapy or conjugates for targeted nuclear drug delivery.

PMID- 29374509
TI  - The level of decoy epitope in PCV2 vaccine affects the neutralizing activity of
      sera in the immunized animals.
AB  - Viral pathogens have evolved a wide range of tactics to evade host immune
      responses and thus propagate effectively. One efficient tactic is to divert host
      immune responses toward an immunodominant decoy epitope and to induce non
      neutralizing antibodies toward this epitope. Therefore, it is expected that the
      amount of decoy epitope in a subunit vaccine can affect the level of neutralizing
      antibody in an immunized animal. In this study, we tested this hypothesis by
      generating an antibody specific to the decoy epitope on the capsid protein of
      porcine circovirus type 2 (PCV2). Using this antibody, we found that two
      commercial vaccines contained statistically different amounts of the decoy
      epitope. The vaccine with lower levels of decoy epitope induced a significantly
      higher level of neutralizing antibody after immunization. This antibody can be
      used as an analytical tool to monitor the quality of a vaccine from batch to
      batch.

PMID- 29374510
TI  - Plasma fatty acyl-carnitines during 8 weeks of overfeeding: relation to diet
      energy expenditure and body composition: the PROOF study.
AB  - OBJECTIVE: Overfeeding is a strategy for evaluating the effects of excess energy
      intake. In this secondary analysis we tested the possibility that different
      levels of dietary protein might differentially modify the response of fatty acyl
      carnitines to overfeeding. METHODS: Twenty-three healthy adult men and women were
      overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15%
      (NPD) or 25% (HPD) protein. Plasma fatty acyl-carnitines were measured by gas
      chromatography/mass spectrometry (GC/MS) at baseline and after 8 weeks of
      overfeeding. Measurements included: body composition by DXA, energy expenditure
      by ventilated hood and doubly-labeled water, fat cell size from subcutaneous fat
      biopsies, and fat distribution by CT scan. RESULTS: Analysis was done on 5 groups
      of fatty acyl-carnitines identified by principal components analysis and 6
      individual short-chain fatty acyl carnitines. Higher protein intake was
      associated with significantly lower 8 week levels of medium chain fatty acids and
      C2, C4-OH and C 6:1, but higher values of C3 and C5:1 acyl-carnitines derived
      from essential amino acids. In contrast energy and fat intake were only weakly
      related to changes in fatty acyl-carnitines. A decease or smaller rise in 8 week
      medium chain acyl-carnitines was associated with an increase in sleeping energy
      expenditure (P = 0.0004), and fat free mass (P < 0.0001) and a decrease in free
      fatty acid concentrations (FFA) (P = 0.0067). In contrast changes in short-chain
      fatty acyl-carnitines were related to changes in resting energy expenditure (P =
      0.0026), and fat free mass (P = 0.0007), and C4-OH was positively related to FFA
      (P = 0006). CONCLUSION: Protein intake was the major factor influencing changes
      in fatty acyl carnitines during overfeeding with higher values of most acyl-fatty
      acids on the low protein diet. The association of dietary protein and fat intake
      may explain the changes in energy expenditure and metabolic variables resulting
      in the observed patterns of fatty acyl carnitines.

PMID- 29374512
TI  - Replacement of a Stenotic Quadricuspid Aortic Valve With a Sutureless Prosthesis.
AB  - Quadricuspid aortic valve is a rare occurrence, usually presenting with
      insufficiency rather than stenosis. We report an aortic valve replacement in a
      septuagenarian with a stenotic quadricuspid aortic valve, achieving a good result
      with a Perceval (Sorin Biomedica Cardio Srl, Sallugia, Italy) sutureless
      bioprosthesis. We emphasize the particular technique of implantation and possible
      pitfalls. Sutureless bioprosthetic valves present a feasible option for aortic
      valve replacement in patients with uncommon valve morphologies, aiming to reduce
      operative time.

PMID- 29374511
TI  - Amiodarone Protocol Provides Cost-Effective Reduction in Postoperative Atrial
      Fibrillation.
AB  - BACKGROUND: Postoperative atrial fibrillation (POAF) after cardiac operations
      results in a significant increase in morbidity, mortality, and health care costs.
      Prophylactic amiodarone has been shown to reduce the incidence of POAF; however,
      the cost-effectiveness of a protocol-driven approach remains unknown. METHODS:
      All patients with a Society of Thoracic Surgeons risk score enrolled in a
      prophylactic amiodarone protocol (n = 153) were propensity score matched 1:3 with
      patients before protocol implementation (n = 3,574). Multivariate logistic and
      linear regressions assessed the relative risks (POAF reduction and adverse
      medication effects) in the matched cohort of amiodarone therapy and costs,
      respectively. TreeAge cost-effectiveness software (TreeAge Software, Inc,
      Williamstown, MA) modeled the effects of prophylactic amiodarone costs,
      complication rates, and quality of life. RESULTS: Of patients eligible for the
      prophylactic amiodarone protocol, 94.3% (281 of 298) were enrolled. Prophylactic
      amiodarone significantly reduced the rate of POAF (25.7% vs 16.8%, p < 0.0001). A
      total of 600 matched patients demonstrate no baseline differences in
      demographics, comorbidities, disease state, or operative factors, with a
      significant reduction in POAF without an increase in other associated
      complications. With the use these adjusted estimates, the prophylactic amiodarone
      protocol demonstrated a cost savings of $458 per patient. Sensitivity analysis
      confirmed the protocol is cost-effective for all protocol-related POAF risk
      reductions below an odds ratio of 0.726. CONCLUSIONS: Implementation of a
      prophylactic amiodarone protocol significantly reduced risk-adjusted rates of
      POAF, with a cost savings of $458 per patient. This analysis demonstrates how
      rigorous quantitative analysis can evaluate the benefits of quality improvement
      projects.

PMID- 29374513
TI  - Screening for Lung Cancer: CHEST Guideline and Expert Panel Report.
AB  - BACKGROUND: Low-dose chest CT screening for lung cancer has become a standard of
      care in the United States in the past few years, in large part due to the results
      of the National Lung Screening Trial. The benefit and harms of low-dose chest CT
      screening differ in both frequency and magnitude. The translation of a favorable
      balance of benefit and harms into practice can be difficult. Here, we update the
      evidence base for the benefit, harms, and implementation of low radiation dose
      chest CT screening. We use the updated evidence base to provide recommendations
      where the evidence allows, and statements based on experience and expert
      consensus where it does not. METHODS: Approved panelists developed key questions
      using the PICO (population, intervention, comparator, and outcome) format to
      address the benefit and harms of low-dose CT screening, as well as key areas of
      program implementation. A systematic literature review was conducted by using
      MEDLINE via PubMed, Embase, and the Cochrane Library. Reference lists from
      relevant retrievals were searched, and additional papers were added. The quality
      of the evidence was assessed for each critical or important outcome of interest
      using the GRADE (Grading of Recommendations, Assessment, Development, and
      Evaluation) approach. Important clinical questions were addressed based on the
      evidence developed from the systematic literature review. Graded recommendations
      and ungraded statements were drafted, voted on, and revised until consensus was
      reached. RESULTS: The systematic literature review identified 59 studies that
      informed the response to the 12 PICO questions that were developed. Key clinical
      questions were addressed resulting in six graded recommendations and nine
      ungraded consensus based statements. CONCLUSIONS: Evidence suggests that low-dose
      CT screening for lung cancer results in a favorable but tenuous balance of
      benefit and harms. The selection of screen-eligible patients, the quality of
      imaging and image interpretation, the management of screen-detected findings, and
      the effectiveness of smoking cessation interventions can affect this balance.
      Additional research is needed to optimize the approach to low-dose CT screening.

PMID- 29374514
TI  - Antioxidative properties and structural features of atypical 2-Cys peroxiredoxin
      from Sebastes schlegelii.
AB  - Atypical 2-Cys peroxiredoxin (Prx5) is an antioxidant protein that exerts its
      antioxidant function by detoxifying different reactive oxygen species (ROS).
      Here, we identified mitochondrial Prx5 from rockfish (SsPrx5) and described its
      specific structural and functional characteristics. The open reading frame (ORF)
      of SsPrx5 (570 bp) was translated into a 190-amino acid polypeptide that
      contained a mitochondrial targeting sequence (MTS), thioredoxin 2 domain, two Prx
      specific signature motifs, and three conserved cysteine residues. Sequence
      comparison indicated that the SsPrx5 protein sequence shared greatest identity
      with teleost orthologs, where the phylogenetic results showed an evolutionary
      position within the fish Prx5. The coding sequence of SsPrx5 was scattered in six
      exons as found in other vertebrates. Additionally, the potent antioxidant
      functions of recombinantly expressed SsPrx5 protein was demonstrated by insulin
      reduction and extracellular H2O2 scavenging both in vitro and in vivo.
      Quantitative real time PCR (qPCR) detected ubiquitous mRNA expression of SsPrx5
      in healthy rockfish tissues, with remarkable expression observed in gill, liver,
      and reproductive tissues. Prompt transcription of SsPrx5 was shown in the immune
      stimulated gill and liver tissues against Streptococcus iniae and
      lipopolysaccharide injection. Taken together, present results suggest the
      indispensable role of SsPrx5 in the rockfish antioxidant defense system against
      oxidative stresses and its role in maintaining redox balance upon pathogen
      invasion.

PMID- 29374515
TI  - Effect of ganoderic acid D on colon cancer Warburg effect: Role of
      SIRT3/cyclophilin D.
AB  - Ganoderic acid D (GAD) is a highly oxygenated tetracyclic triterpenoid. This
      study aims to assess the effects of GAD on the energy metabolism of colon cancer
      through the regulation of SIRT3 expression and whether this effect is related to
      acetylated cyclophilin D. The results demonstrated that GAD inhibits the energy
      reprogramming of colon cancer cells including glucose uptake, lactate production,
      pyruvate and acetyl-coenzyme production in colon cancer cells. Meanwhile, GAD
      upregulated the protein expression of SIRT3. Furthermore, the interruption of
      SIRT3 expression significantly reversed all the effects of SIRT3 on the energy
      reprogramming of colon cancer. In addition, GAD induced the deacetylated
      cyclophilin D (CypD) by SIRT3, whereas SIRT3-shRNA inhibited its combining effect
      on CypD. The energy reprogramming effects of GAD on colon cancer seem to be
      mediated by SIRT3 upregulation via acetylated CypD inhibition.

PMID- 29374517
TI  - Association analysis of norepinephrine transporter polymorphisms and
      methylphenidate response in ADHD patients.
AB  - AIMS: Methylphenidate (MPH) is the most frequently prescribed drug in Attention
      Deficit Hyperactivity Disorder (ADHD). Hitherto mostly the dopamine transporter
      gene has been studied in MPH-response and only a few studies analyzed the
      norepinephrine transporter (NET, SLC6A2) gene, although MPH is a potent inhibitor
      of both dopamine and norepinephrine transporters. We aimed to analyze this
      monoamine transporter gene in relation to ADHD per se and MPH-response in
      particular to gain further knowledge in ADHD pharmacogenetics using a Caucasian
      sample. METHODS: Six single nucleotide polymorphisms (rs28386840, rs2242446,
      rs3785143, rs3785157, rs5569, rs7194256 SNP) were studied across the NET gene in
      163 ADHD children (age: 9.3+/-2.6; 86.5% male) using ADHD-RS hyperactivity
      impulsivity and inattention scales. For case-control analysis 486 control
      subjects were also genotyped. At the MPH-response analysis responders had minimum
      25% decrease of ADHD-RS total score after 2months of treatment, and chi-square
      test compared 90 responders and 32 non-responders, whereas ANOVA was used to
      assess symptom improvement after the first month among the 122 ADHD patients.
      RESULTS: The classical case-control analysis did not yield any association with
      ADHD diagnosis, which was supported by meta-analysis conducted on the available
      genetic data (combining previously published and the present studies). On the
      other hand, the intronic rs3785143 showed nominal association with inattention
      symptoms (p=0.01). The haplotype analysis supported this association, and
      indicated the importance of the first haploblock encompassing the intronic and 2
      promoter SNPs. With MPH-response only the promoter rs28386840 showed nominal
      association: Those with at least one T-allele were overrepresented in the
      responder group (42% vs 19%, p=0.08), and they had better improvement on the
      hyperactivity-impulsivity scale compared to the AA genotype (p=0.04). CONCLUSION:
      Although none of our single SNP findings remained significant after correcting
      for multiple testing, our results from the MPH-response analysis indicate the
      potential importance of promoter variants in the NET gene.

PMID- 29374519
TI  - Ribosomal protein L18 is an essential factor that promote rice stripe virus
      accumulation in small brown planthopper.
AB  - Rice stripe virus (RSV) transmitted by the vector, small brown planthopper
      (SBPH), can cause a severe rice disease. The nucleocapsid (N) protein is the
      major component of RSV ribonucleoprotein particles (RNPs), and it plays important
      roles in viral persistent-propagative transmission by SBPH. To gain further
      insights into the vector components enabling RSV transmission, a GAL4-based yeast
      two-hybrid system was utilized to find unknown vector factors that interact with
      the N protein. Thirteen different proteins were identified as factors that
      interact with the N protein. The interaction between 60S ribosomal protein L18
      (RPL18) and the N protein was further studied. Although the expression of RPL18
      was not altered in insects during RSV infection, RPL18 was validated to bind
      directly to RSV RNPs and interact with RSV N protein. Knockdown of RPL18
      dramatically reduced viral RNA and protein levels, especially viral protein
      expression, indicating a requirement for RPL18 in RSV translation and
      replication. Our results provide evidence that RPL18 is a critical factor
      required for RSV accumulation in SBPH, which suggests that the vector factor
      RPL18 may be as a potential target to develop for controlling the transmission of
      rice virus.

PMID- 29374518
TI  - In vitro stabilization and in vivo improvement of ocular pharmacokinetics of the
      multi-therapeutic agent baicalin: Delineating the most suitable vesicular
      systems.
AB  - Baicalin is a multi-purpose flavonoid used in the treatment of different ocular
      diseases. Owing to its poor stability in basic pH and its poor solubility, a
      suitable carrier system is needed to enhance its ocular therapeutic potential.
      Therefore, the objective of this work was to prepare and contrast different
      baicalin vesicular systems; namely liposomes, penetration enhancer vesicles PEVs
      and transfersomes. Results revealed that baicalin vesicles exhibited suitable
      particle size and zeta potential, high entrapment efficiency and controlled
      release. Depending on the vesicular composition, selected formulations were able
      to resist physical changes of particle size, zeta potential, entrapment
      efficiency and in vitro release after storage for 3 months, while retarding the
      degradation of baicalin. Selected vesicular formulations displayed equivalent or
      superior antioxidant potential compared to baicalin solution, with absolute
      superiority over ascorbic acid reference, while demonstrating sterilization
      endurance and safety on ocular tissues. Pharmacokinetic studies revealed that
      transfersomes displayed the fastest onset of action, while liposomes displayed
      the highest extent of absorption as concluded from the Tmax, Cmax, and AUC0
      infinity values with 4-5 folds increase in bioavailability compared to baicalin
      control solution. This delineates baicalin vesicular systems as a promising
      platform for treatment of ocular diseases such as inflammation, cataract and
      diabetic retinopathy.

PMID- 29374520
TI  - Evaluation of CpG-SNPs in miRNA promoters and risk of breast cancer.
AB  - CpG-SNPs in gene promoter regions are proposed to be associated with multiple
      diseases. To date, few studies have focused on the associations between CpG-SNPs
      in miRNA promoters and the risk of breast cancer. In this study, 138 miRNAs
      differentially expressed between breast cancer and non-cancer tissues (fold
      change >2, P < 0.05) were identified using The Cancer Genome Atlas (TCGA)
      Research database. In total, 13 SNPs were selected in the promoters of the miRNAs
      and were evaluated in a case-control study of Chinese women including 1486 cases
      and 1519 controls. After multivariate logistic regression analysis, we found that
      three CpG-SNPs: rs1190983, rs155247, and rs62382272, were significantly
      associated with breast-cancer susceptibility in the population (Additive model:
      rs1190983: adjusted OR = 0.88, 95% CI: 0.79-0.99, P = 0.034; rs155247: adjusted
      OR = 0.83, 95% CI: 0.74-0.93, P = 0.002; rs62382272: adjusted OR = 1.24, 95% CI:
      1.04-1.47, P = 0.016). eQTL analysis showed that these three SNPs were correlated
      with the expression of the related miRNAs in TCGA breast cancer tissues (P =
      0.006,0.009,0.001 for rs1190983, rs155247, and rs62382272). Furthermore,
      rs1190983 was found to be associated with CpG site (cg20488673) methylation
      (meQTL) (P = 0.004), which was in turn correlated with miR-342 expression (P =
      0.016). These findings indicated that the three CpG-SNPs in the promoters of
      miRNAs were likely to possess important biological functions to breast cancer in
      the Han Chinese population.

PMID- 29374521
TI  - MicroRNA-200a regulates adipocyte differentiation in the domestic yak Bos
      grunniens.
AB  - The domestic yak (Bos grunniens) is a culturally important animal that lives at
      high altitude and is farmed by Tibetan herders for its meat, milk, and other
      animal by-products. Within the animal, adipose tissue is an important store and
      source of energy and is used to maintain adequate body temperature during the
      extended cold seasons. Exploring the biomolecular role of microRNAs (miRNAs) in
      the regulation of growth, development, and metabolism of yak adipocytes may
      provide valuable insights into the physiology of adipogenesis in the yak. This
      study investigated whether and how miR-200a (a miRNA recently reported to promote
      adipogenesis in ST2 bone marrow stromal cells) regulates adipocyte
      differentiation in the yak. Expression levels of miR-200a gradually increased
      during day 0 to day 8 of adipocyte differentiation, and transfection of
      adipocytes with miR-200a enhanced lipid accumulation and triglyceride content
      compared to control (un-transfected) adipocytes. We additionally verified (using
      qRT-PCR analysis) that miR-200a increased the expression of adipocyte-specific
      genes involved in lipogenic transcription (PPARgamma, ELVOL, and C/EBPalpha),
      fatty acid synthesis (ACC, ACS, SCD, and FAS), and fatty acid transport (DGAT,
      LPL, and FABP4). We also found that transfection of adipocytes with miR-200a
      resulted in suppression of the levels of noncanonical Wnt signaling transcription
      factors (Wnt5a, TAK1, and NLK). These results indicate that miRNA-200a plays an
      important role in promoting yak adipocyte differentiation that may operate via
      the suppression of noncanonical Wnt signaling.

PMID- 29374522
TI  - Inequity aversion is observed in common marmosets but not in marmoset models of
      autism induced by prenatal exposure to valproic acid.
AB  - Humans and various nonhuman primates respond negatively to inequity not in their
      favor (i.e., inequity aversion), when inequity between two individuals is
      introduced. Common marmosets, a highly prosocial species, further discriminated
      between human actors who reciprocated in social exchanges, and those who did not.
      Conversely, marmoset models of autism, induced via prenatal exposure to valproic
      acid (VPA marmosets), did not discriminate. Interestingly, previous studies of
      inequity aversion in marmosets have produced negative results, or were limited to
      males. Recent studies suggest that inequity aversion is highly influenced by the
      tasks employed. Here we show inequity aversion in both male and female marmosets
      using a novel task which required a relatively long duration of response.
      Marmosets were required to hold a spoon for 2 s to receive a reward. Marmosets
      successfully performed the task when they observed an unfamiliar conspecific
      partner obtaining the same reward (equity test). However, when they witnessed the
      partner receiving a more attractive reward for equal effort (inequity test),
      unexposed marmosets, which were not exposed to either valproic acid or saline
      during the fetal period refused to respond. This inequity aversion was not
      observed in unexposed marmosets when the partner was absent. In contrast,
      marmosets with fetal exposure to valproic acid (VPA marmosets) successfully
      executed the task irrespective of their partners' reward conditions. As prenatal
      exposure to valproic acid is a well-known procedure to induce autism spectrum
      disorder (ASD)-like behaviors in rodents, we propose that VPA marmosets failed to
      show inequity aversion due to weak social motivation or interest towards others.

PMID- 29374516
TI  - The vicious cycle of itch and anxiety.
AB  - Chronic itch is associated with increased stress, anxiety, and other mood
      disorders. In turn, stress and anxiety exacerbate itch, leading to a vicious
      cycle that affects patient behavior (scratching) and worsens disease prognosis
      and quality of life. This cycle persists across chronic itch conditions of
      different etiologies and even to some extent in healthy individuals, suggesting
      that the final common pathway for itch processing (the central nervous system)
      plays a major role in the relationship between itch and anxiety. Pharmacological
      and nonpharmacological treatments that reduce anxiety have shown promising anti
      itch effects. Further research is needed to establish specific central mechanisms
      of the itch-anxiety cycle and provide new targets for treatment.

PMID- 29374523
TI  - Antigen 5-spiked Vespula and Polistes venom extracts for Vespid allergy
      diagnostics: A French multicenter study.

PMID- 29374524
TI  - Do we need to keep playing this tune?

PMID- 29374525
TI  - Periprosthetic joint infection caused by anaerobes. Retrospective analysis
      reveals no need for prolonged cultivation time if sensitive supplemented growth
      media are used.
AB  - BACKGROUND: In microbiological diagnosis of periprosthetic joint infection (PJI)
      culture media and incubation time are controversially discussed, especially if
      anaerobic bacteria are the causative agent. This study was conducted to
      demonstrate the influence of sensitive supplemented growth media on the duration
      of culturing anaerobes. METHODS: Twenty-five consecutive cases were included in
      this retrospective study. For definition of PJI, the criteria of the
      Musculoskeletal Infection Society (MSIS) were considered. Histopathological
      analysis was interpreted according to the classification by Krenn et al. The
      quantity and time to positivity of detected anaerobes were monitored.
      Furthermore, antimicrobial activity within the tissue and sonicate fluid was
      phenotypically tested. RESULTS: In all cases, even if the patients had received
      antibiotics before recovery, culture of anaerobes (Propionibacterium species,
      Finegoldia magna, Parvimonas micra and Robinsoniella peoriensis), both from
      tissue samples and prosthetic components, first became detectable in supplemented
      liver thioglycollate broth within six days (median: four days). CONCLUSION:
      Recommendations for prolonged cultivation for up to 14 days mostly aim at
      detection of anaerobes. Here we present a laboratory procedure that can shorten
      cultivation time considerably.

PMID- 29374526
TI  - Small sustainable monetary incentives versus charitable donations to promote
      exercise: Rationale, design, and baseline data from a randomized pilot study.
AB  - Regular physical activity (PA) enhances weight-loss and reduces risk of chronic
      disease. However, as few as 10% of U.S. adults engage in regular PA. Incentive
      programs to promote PA have shown some promise, but have typically used
      incentives that are too large to sustain over time and have not demonstrated
      habit formation or been tested in community settings. This report presents the
      rationale and design of a randomized pilot study testing the feasibility and
      preliminary efficacy of small monetary incentives for PA (n=25) versus charitable
      donations in the same amount (n=25) versus control (n=25) over 12months among 75
      low-active but otherwise healthy adults at a local YMCA. Incentives are based on
      YMCA attendance, which is verified by electronic swipe card data and is the
      primary study outcome, with self-reported minutes/week of PA assessed as a
      secondary outcome. Incentives are intentionally small enough-$1/session, maximum
      of $5/week-such that they could be indefinitely sustained by community
      organizations, privately-owned health clubs, healthcare organizations, or
      employers (e.g., employer fitness facilities). Costs of the incentive program for
      the sponsoring organization may be partially offset by increases in membership
      resulting from the appeal of the program. Moreover, if efficacious, the
      charitable donation incentive program may have the added benefit of building
      social capital for the sponsoring organization and potentially serving as a tax
      write-off, thus further offsetting the cost of the incentives. Findings will also
      have implications for the use of financially sustainable community-based
      incentive programs for other health-related behaviors (e.g., weight loss,
      smoking).

PMID- 29374527
TI  - Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: A
      Systematic Review and Meta-Analysis.
AB  - Autologous hematopoietic stem cell transplantation (AHSCT) has been proposed as a
      therapeutic modality for severe systemic sclerosis (SSc). We set out to
      systematically review and meta-analyze the efficacy and safety of AHSCT in SSc.
      Randomized controlled trials (RCTs) and retrospective studies comparing AHSCT
      with standard immunosuppressive therapy were included. Of 363 titles screened
      from multiple databases, 15 were extracted for further investigation, and 4 met
      inclusion criteria (3 RCTs and 1 retrospective analysis). The control arm was
      monthly cyclophosphamide in all the RCTs and the majority of patients in the
      retrospective analysis (69%). Compared with the control, AHSCT reduced all-cause
      mortality (risk ratio [RR], .5 [95% confidence interval, .33 to .75]) and
      improved skin thickness (modified Rodnan skin score mean difference [MD], 10.62
      [95% CI, -14.21 to 7.03]), forced vital capacity (MD, 9.58 [95% CI, 3.89 to
      15.18]), total lung capacity (MD, 6.36 [95% CI, 1.23 to 11.49]), and quality of
      life (physical 36-Item Short Form Health Survey [MD, 6.99 (95% CI, 2.79 to
      11.18)]). Treatment-related mortality considerably varied between trials but was
      overall higher with AHSCT (RR, 9.00 [95% CI, 1.57 to 51.69]). The risk of bias
      for studies included in the analysis was low. Overall, AHSCT reduces the risk of
      all-cause mortality and has properties of a disease-modifying antirheumatic
      treatment in SSc. Further investigation is warranted for refining patient
      selection and timing of transplantation.

PMID- 29374528
TI  - Breakage and drying behaviour of granules in a continuous fluid bed dryer:
      Influence of process parameters and wet granule transfer.
AB  - Although twin screw granulation has already been widely studied in recent years,
      only few studies addressed the subsequent continuous drying which is required
      after wet granulation and still suffers from a lack of detailed understanding.
      The latter is important for optimisation and control and, hence, a cost-effective
      practical implementation. Therefore, the aim of the current study is to increase
      understanding of the drying kinetics and the breakage and attrition phenomena
      during fluid bed drying after continuous twin screw granulation. Experiments were
      performed on a continuous manufacturing line consisting of a twin-screw
      granulator, a six-segmented fluid bed dryer, a mill, a lubricant blender and a
      tablet press. Granulation parameters were fixed in order to only examine the
      effect of drying parameters (filling time, drying time, air flow, drying air
      temperature) on the size distribution and moisture content of granules (both of
      the entire granulate and of size fractions). The wet granules were transferred
      either gravimetrically or pneumatically from the granulator exit to the fluid bed
      dryer. After a certain drying time, the moisture content reached an equilibrium.
      This drying time was found to depend on the applied airflow, drying air
      temperature and filling time. The moisture content of the granules decreased with
      an increasing drying time, airflow and drying temperature. Although smaller
      granules dried faster, the multimodal particle size distribution of the granules
      did not compromise uniform drying of the granules when the target moisture
      content was achieved. Extensive breakage of granules was observed during drying.
      Especially wet granules were prone to breakage and attrition during pneumatic
      transport, either in the wet transfer line or in the dry transfer line. Breakage
      and attrition of granules during transport and drying should be anticipated early
      on during process and formulation development by performing integrated
      experiments on the granulator, dryer and mill.

PMID- 29374529
TI  - Raman-markers of X-ray radiation damage of proteins.
AB  - Despite their high relevance, the mechanisms of X-ray radiation damage on protein
      structure yet have to be completely established. Here, we used Raman
      microspectrophotometry to follow X-ray-induced chemical modifications on the
      structure of the model protein bovine pancreatic ribonuclease (RNase A). The
      combination of dose-dependent Raman spectra and ultrahigh resolution (eight
      structures solved using data collected between 0.85 and 1.17 A resolution on the
      same single crystal) allowed direct observation of several radiation damage
      events, including covalent bond breakages and formation of radicals. Our results
      are relevant for analytical photodamage detection and provide implications for a
      detailed understanding of the mechanisms of photoproduct formation.

PMID- 29374530
TI  - ESI-MS measurements for the equilibrium constants of copper(II)-insulin
      complexes.
AB  - Trace elements regulate many biological reactions in the body. Copper(II) is
      known as one of trace elements and capable of binding to proteins. Insulin is a
      blood glucose-lowering peptide hormone and it is secreted by the pancreatic beta
      cells. In this study, Cu(II)-insulin complexes were investigated by using ESI-MS
      method. Insulin molecule gives ESI-MS peaks at +4, +5, +6 and +7 charged states.
      Cu(II)-insulin complexes can be monitored and quantified on the ESI-MS spectra as
      the shifted peaks according to insulin peaks. The solutions of Cu(II)-insulin
      complexes at different pHs and mole ratios of Cu(II) ions to insulin molecule
      were measured on the ESI-MS. The highest complex formation ratio for Cu(II)
      insulin were found at pH 7. The multiple bindings of Cu(II) ions to insulin
      molecule was observed. The formation equilibrium constants of Cu(II)-insulin
      complexes were calculated as Kf1: 3.34 * 104, Kf2: 2.99 * 104, Kf3: 7.00 * 103
      and Kf4:2.86 * 103. The specific binding property of Cu(II) ions was controlled
      by using different spray ion sources including electrospray and nano
      electrospray. The binding property of Cu(II) also investigated by MS/MS
      fragmentation. It was concluded from the ESI-MS measurements that Cu(II) ion has
      a high affinity to insulin molecules to form stable complexes.

PMID- 29374531
TI  - An antioxidant alpha-glucan from Cladina rangiferina (L.) Nyl. and its protective
      effect on alveolar epithelial cells from Pb2+-induced oxidative damage.
AB  - Air pollution is a serious global health problem nowadays. So, it is an emergency
      to pay sufficient attention to treat and prevent the diseases caused by air
      pollution, especially respiratory disease and lung damage. Cladina rangiferina
      (L.) Nyl. is an edible lichen that has been used in medicinal diets to treat
      respiratory and other diseases for over 500 years. In this study, a water-soluble
      polysaccharide, CRWP-P, was obtained from C. rangiferina by hot-water extraction,
      freeze-thawing separation, and Fehling reagent purification. Structural analysis
      showed that CRWP-P is a linear alpha-(1 -> 3),(1 -> 4)-d-glucan without branches.
      Its Mw was determined to be 1.05 * 105 Da. Its (1,3)-alpha-d-glucopyranosyl:
      (1,4)-alpha-d-glucopyranosyl ratio is approximately 1:2. Antioxidant activity
      assay showed that C. rangiferina polysaccharides, especially CRWP-P, had
      appreciable DPPH radical-scavenging activity and reducing power. Notably, they
      could effectively decrease cell breakdown and ROS generation, inhibit lipid
      peroxidation, increase key antioxidase activity, and promote glutathione redox
      cycling in Pb2+-oxidative injured A549 alveolar epithelium cells. Overall, the
      results of this study indicated that C. rangiferina polysaccharides, especially
      CRWP-P, have the potential to be natural antioxidants for the treatment of lung
      oxidative damage induced by lead of air pollutants.

PMID- 29374532
TI  - Protein folding, misfolding and aggregation: A tale of constructive to
      destructive assembly.
AB  - The newly synthesized unfolded polypeptide attains its functional and unique
      three-dimensional conformation through the process of protein folding for which
      several models have been proposed. The protein misfolding diseases include
      Alzheimer's, Parkinson's and Cataract which are result of formation of amyloid or
      amorphous aggregates, respectively. The distinction in morphology shows relation
      with the melting temperature (Tm). The temperatures near or slightly higher than
      Tm induces amyloids while much higher or low temperature mediate amorphous
      aggregation. The aggregation is not always deleterious rather it also performs
      several important cellular functions essential for survival wide range of
      organisms called as functional amyloids. Protein gets modulated by several
      modulators which mediate the aggregation, acceleration, delay, transformations,
      inhibition and disaggregation of protein aggregates. The exclusive properties of
      inhibition and disaggregation displayed by various molecules can be employed to
      treat the life threatening disorders.

PMID- 29374533
TI  - Circadian control of p75 neurotrophin receptor leads to alternate activation of
      Nrf2 and c-Rel to reset energy metabolism in astrocytes via brain-derived
      neurotrophic factor.
AB  - Circadian clock genes regulate energy metabolism partly through neurotrophins in
      the body. The low affinity neurotrophin receptor p75NTR is a clock component
      directly regulated by the transcriptional factor Clock:Bmal1 complex. Brain
      derived neurotrophic factor (BDNF) is expressed in the brain and plays a key role
      in coordinating metabolic interactions between neurons and astrocytes. BDNF
      transduces signals through TrkB and p75NTR receptors. This review highlights a
      novel molecular mechanism by which BDNF via circadian control of p75NTR leads to
      daily resetting of glucose and glycogen metabolism in brain astrocytes to
      accommodate their functional interaction with neurons. Astrocytes store glycogen
      as an energy reservoir to provide active neurons with the glycolytic metabolite
      lactate. Astrocytes predominantly express the truncated receptor TrkB.T1 which
      lacks an intracellular receptor tyrosine kinase domain. TrkB.T1 retains the
      capacity to regulate cell morphology through regulation of Rho GTPases. In
      contrast, p75NTR mediates generation of the bioactive lipid ceramide upon
      stimulation with BDNF and inhibits PKA activation. As ceramide directly activates
      PKCzeta, we discuss the importance of the TrkB.T1-p75NTR-ceramide-PKCzeta
      signaling axis in the stimulation of glycogen and lipid synthesis and activation
      of RhoA. Ceramide-PKCzeta-casein kinase 2 signaling activates Nrf2 to support
      oxidative phosphorylation via upregulation of antioxidant enzymes. In the absence
      of p75NTR, TrkB.T1 functionally interacts with adenosine A2AR and dopamine D1R
      receptors to enhance cAMP-PKA signaling and activate Rac1 and NF-kappaB c-Rel,
      favoring glycogen hydrolysis, gluconeogenesis and aerobic glycolysis. Thus,
      diurnal changes in p75NTR levels in astrocytes resets energy metabolism via BDNF
      to accommodate their metabolic interaction with neurons.

PMID- 29374534
TI  - Thymoquinone-based nanotechnology for cancer therapy: promises and challenges.
AB  - Thymoquinone (TQ), the active ingredient of black seed, is a promising anticancer
      molecule that inhibits cancer cell growth and progression in vitro and in vivo.
      Despite the promising anticancer activities of TQ, its translation to the clinic
      is limited by its poor bioavailability and hydrophobicity. As such, we and others
      encapsulated TQ in nanoparticles to improve its delivery and limit undesirable
      cytotoxicity. These TQ-nanoparticle formulations showed improved anticancer and
      anti-inflammatory activities when compared with free TQ. Here, we provide an
      overview of the various TQ-nanoparticle formulations, highlight their superior
      efficacy and discuss up-to-date solutions to further enhance TQ bioavailability
      and anticancer activity, thus improving potential for clinical translation.

PMID- 29374535
TI  - Cognitive Biases in Children and Adolescents With Chronic Pain: A Review of
      Findings and a Call for Developmental Research.
AB  - : Cognitive biases that emphasize bodily harm, injury, and illness could play a
      role in the maintenance of chronic pain by facilitating fear and avoidance.
      Whereas extensive research has established attention, interpretation, and memory
      biases in adults with chronic pain, far less is known about these same biases in
      children and adolescents with pain. Studying cognitive biases in attention,
      interpretation, and memory in relation to pain occurring in youth is important
      because youth is a time when pain can first become chronic, and when
      relationships between cognitive biases and pain outcomes emerge and stabilize.
      Thus, youth potentially offers a time window for the prevention of chronic pain
      problems. In this article, we summarize the growing corpus of data that have
      measured cognitive biases in relation to pediatric pain. We conclude that
      although biases in attention, interpretation, and memory characterize children
      and adolescents with varying pain experiences, questions regarding the direction,
      magnitude, nature, and role of these biases remain. We call for independent
      extension of cognitive bias research in children and adolescents, using well
      powered longitudinal studies with wide age ranges and psychometrically sound
      experimental measures to clarify these findings and any developmental trends in
      the links between cognitive biases and pain outcomes. PERSPECTIVE: This article
      provides a rationale for the theoretical and practical importance of studying the
      role of cognitive biases in children and adolescents with chronic pain, which has
      to date, been relatively understudied. Existing findings are reviewed critically,
      and recommendations for future research are offered.

PMID- 29374536
TI  - Cognitive Flexibility Deficits Following 6-OHDA Lesions of the Rat Dorsomedial
      Striatum.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder marked by severe motor
      deficits and reduced striatal dopamine levels. PD patients also commonly exhibit
      cognitive flexibility impairments, e.g., probabilistic reversal learning deficits
      that limit daily living. However, less is known about how decreased striatal
      dopamine signaling affects cognitive flexibility. Past studies indicate that the
      rat dorsomedial striatum is a striatal subregion that supports cognitive
      flexibility. Because PD patients exhibit probabilistic reversal learning
      deficits, the present experiment investigated whether the neurotoxin 6
      hydroxydopamine (6-OHDA) injected into the dorsomedial striatum of male Long
      Evans rats affects the acquisition and/or reversal learning of a spatial
      discrimination using a probabilistic learning procedure (80/20). Behavioral
      testing was conducted in a cross maze that occurred across two consecutive days.
      Rats with 6-OHDA lesions were not impaired on acquisition, but were impaired in
      reversal learning compared to that of sham controls. In reversal learning,
      dorsomedial striatal dopamine depletion led to initial perseveration of the
      previously correct choice pattern, as well as an impairment in maintaining the
      new choice pattern after initially selected (regressive errors). A 6-OHDA lesion
      in the dorsomedial striatum also significantly increased 'lose-shift'
      probabilities in reversal learning suggesting that reduced dopamine signaling in
      this striatal area increased sensitivity to negative feedback ultimately
      impairing the maintenance of a new response pattern. Overall, the findings
      suggest that dopamine reduction in this striatal subregion can serve as a useful
      model to test novel treatments for ameliorating cognitive flexibility deficits in
      PD.

PMID- 29374537
TI  - HSP70 Facilitates Memory Consolidation of Fear Conditioning through MAPK Pathway
      in the Hippocampus.
AB  - Heat shock proteins of the 70-kDa (HSP70) family are cytoprotective molecular
      chaperones that are present in neuronal cells and can be induced by a variety of
      homeostatically stressful situations (not only proteostatic insults), but also by
      synaptic activity, including learning tasks. Physiological stimuli that induce
      long-term memory formation are also capable of stimulating the synthesis of HSP70
      through the activation of heat shock transcription factor-1 (HSF1). In this
      study, we investigated the influence of HSP70 on fear memory consolidation and
      MAPK activity. Male rats were trained in contextual fear conditioning task and
      HSP70 content was analyzed by western blot in the hippocampus at different time
      points. We observed rapid and transient elevations in HSP70 60 min following
      training. Double immunofluorescence with GFAP and HSP72 revealed that astrocytes
      were not the site for HSP72 induction by CFC training. HSP72 distribution
      markedly surrounded synapses between Shaffer collateral and CA1 pyramidal cells.
      Infusion of recombinant HSP70 (hspa1a) into the dorsal hippocampus immediately
      after training facilitated memory consolidation and enhanced ERK activity while
      decreasing the activated forms of JNK and p38 in the hippocampus. Blocking
      endogenous extracellular HSP70 through the administration of specific antibody
      did not produce any further effect on memory consolidation when applied
      immediately after training, suggesting that it is indeed acting intracellularly.
      Induction of HSP70 after fear conditioning is fast and can act as a signaling
      molecule, modulating MAPK downstream signaling during memory consolidation in the
      hippocampus, which is crucial for fear memory formation.

PMID- 29374538
TI  - Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by
      Reducing the Activity of Striatal Cholinergic Interneurons.
AB  - Histamine H3 receptors are widely distributed Gi-coupled receptors whose
      activation reduces neuronal activity and inhibits release of numerous
      neurotransmitters. Although these receptors are abundantly expressed in the
      striatum, their modulatory role on activity-dependent dopamine release is not
      well understood. Here, we observed that histamine H3 receptor activation
      indirectly diminishes dopamine overflow in the ventral striatum by reducing
      cholinergic interneuron activity. Acute brain slices from C57BL/6 or
      channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine
      transients evoked either electrically or optogenetically were measured by fast
      scan cyclic voltammetry. The H3 agonist alpha-methylhistamine significantly
      reduced electrically- evoked dopamine overflow, an effect blocked by the
      nicotinic acetylcholine receptor antagonist dihydro-beta-erythroidine, suggesting
      involvement of cholinergic interneurons. None of the drug treatments targeting H3
      receptors affected optogenetically evoked dopamine overflow, indicating that
      direct H3-modulation of dopaminergic axons is unlikely. Next, we used qPCR and
      confirmed the expression of histamine H3 receptor mRNA in cholinergic
      interneurons, both in ventral and dorsal striatum. Activation of H3 receptors by
      alpha-methylhistamine reduced spontaneous firing of cholinergic interneurons in
      the ventral, but not in the dorsal striatum. Resting membrane potential and
      number of spontaneous action potentials in ventral-striatal cholinergic
      interneurons were significantly reduced by alpha-methylhistamine. Acetylcholine
      release from isolated striatal synaptosomes, however, was not altered by alpha
      methylhistamine. Together, these results indicate that histamine H3 receptors are
      important modulators of dopamine release, specifically in the ventral striatum,
      and that they do so by decreasing the firing rate of cholinergic neurons and,
      consequently, reducing cholinergic tone on dopaminergic axons.

PMID- 29374539
TI  - Differential Processing by Two Olfactory Subsystems in the Honeybee Brain.
AB  - Among insects, Hymenoptera present a striking olfactory system with a clear
      neural dichotomy from the periphery to higher order centers, based on two main
      tracts of second-order (projection) neurons: the medial and lateral antennal lobe
      tracts (m-ALT and l-ALT). Despite substantial work on this dual pathway, its
      exact function is yet unclear. Here, we ask how attributes of odor quality and
      odor quantity are represented in the projection neurons (PNs) of the two
      pathways. Using in vivo calcium imaging, we compared the responses of m-ALT and l
      ALT PNs of the honey bee Apis mellifera to a panel of 16 aliphatic odorants, and
      to three chosen odorants at eight concentrations. The results show that each
      pathway conveys differential information about odorants' chemical features or
      concentration to higher order centers. While the l-ALT primarily conveys
      information about odorants' chain length, the m-ALT informs about odorants'
      functional group. Furthermore, each tract can only predict chemical distances or
      bees' behavioral responses for odorants that differ according to its main
      feature, chain length or functional group. Generally l-ALT neurons displayed more
      graded dose-response relationships than m-ALT neurons, with a correspondingly
      smoother progression of inter-odor distances with increasing concentration.
      Comparison of these results with previous data recorded at AL input reveals
      differential processing by local networks within the two pathways. These results
      support the existence of parallel processing of odorant features in the insect
      brain.

PMID- 29374540
TI  - Evaluation of oxidative stress and brain-derived neurotrophic factor levels
      related to crack-use detoxification.
AB  - Crack is a central nervous system stimulant extracted from the Erythroxylum coca
      plant. It is considered the most potent and addictive form of cocaine, and its
      euphoric effects are attained within a few seconds after consumption. Alteration
      of biological markers of oxidative stress and brain-derived neurotrophic factor
      (BDNF) could be related to the severity of crack withdrawal symptoms in patients
      undergoing rehabilitation. Thus, the objective of this study was to evaluate if
      the crack consumption and the drug detoxification process during 14 days in
      hospitalization regime was able to modify the oxidative status and BDNF levels,
      in male crack-abstinent patients. The crack detoxification process increased the
      glutathione (GSH), total thiol content (GST), nitric oxide (NO), and superoxide
      dismutase (SOD) levels, and reduced the mean BDNF levels. Moreover, a positive
      correlation was found between the number of hospital admission days and SOD
      values and between the GST levels and crack-use time after 14 days of
      detoxification. Furthermore, a negative correlation between the frequency of
      crack use and NO levels on the first day of hospitalization was also found. In
      conclusion, the results of this study indicated that crack consumption causes
      increased oxidative stress in drug users and that the detoxification process
      during 14 days was sufficient to improve oxidative parameters and antioxidant
      defenses of the patients, which could positively contribute to rehabilitation
      process. In addition, we also observed a great variability in the BDNF levels of
      the patients during the detoxification process, resulting in a reduction in the
      mean values of this neurotrophin.

PMID- 29374541
TI  - Healthy full-term infants' brain responses to emotionally and linguistically
      relevant sounds using a multi-feature mismatch negativity (MMN) paradigm.
AB  - We evaluated the feasibility of a multi-feature mismatch negativity (MMN)
      paradigm in studying auditory processing of healthy newborns. The aim was to
      examine the automatic change-detection and processing of semantic and emotional
      information in speech in newborns. Brain responses of 202 healthy newborns were
      recorded with a multi-feature paradigm including a Finnish bi-syllabic pseudo
      word/ta-ta/as a standard stimulus, six linguistically relevant deviant stimuli
      and three emotionally relevant stimuli (happy, sad, angry). Clear responses to
      emotional sounds were found already at the early latency window 100-200 ms,
      whereas responses to linguistically relevant minor changes and emotional stimuli
      at the later latency window 300-500 ms did not reach significance. Moreover,
      significant interaction between gender and emotional stimuli was found in the
      early latency window. Further studies on using multi-feature paradigms with
      linguistic and emotional stimuli in newborns are needed, especially those
      containing of follow-ups, enabling the assessment of the predictive value of
      early variations between subjects.

PMID- 29374542
TI  - BAFfling pathologies: Alterations of BAF complexes in cancer.
AB  - To activate or repress specific genes, chromatin is constantly modified by
      chromatin-remodeling complexes. Among these complexes, the SWItch/Sucrose Non
      Fermenting (SWI/SNF) complex, also referred to as BRG1-Associated Factor (BAF)
      complex, moves the nucleosome along chromatin using energy provided by ATP
      hydrolysis. In mammalian organisms, the SWI/SNF complex is composed of 10-15
      subunits, depending on cell type, and a defect in one of these subunits can have
      dramatic consequences. In this review we will focus on the alterations identified
      in the SWI/SNF (BAF) complex subunits that lead to cancerous pathologies. While
      SMARCB1 was the first mutated subunit to be reported in a majority of malignant
      rhabdoid tumors, the advent of next-generation sequencing allowed the discovery
      of mutations in various SWI/SNF subunits within a broad spectrum of cancers. In
      most cases, the mutation leads to a loss of expression or to a truncated subunit
      unable to perform its function. Even though it is now commonly acknowledged that
      approximately 20% of all cancers present a mutation in a SWI/SNF subunit, some
      cancers are associated to a specific alteration of a SWI/SNF subunit, which acts
      either as tumor suppressor genes or as oncogenes, and therefore constitute
      diagnostic or prognostic biomarkers. Consistently, therapeutic strategies
      targeting SWI/SNF subunits or the genes affected downstream have been revealed to
      treat cancers.

PMID- 29374544
TI  - Phosphorylation of the outer membrane mitochondrial protein OM64 influences
      protein import into mitochondria.
AB  - Mitochondrial localized proteins are mostly synthesized in the cytosol and
      translocated across the outer mitochondrial membrane via the translocase of the
      outer membrane (TOM) complex. Although the channel protein is conserved among
      eukaryotes, the receptor proteins are more divergent and show features specific
      to the plant lineage. OM64, which is a paralogue of the chloroplast docking
      protein Toc64, is unique to plants. However, due to the presence of a cytosolic
      exposed TPR domain it might functionally replace yeast/mammalian Tom70, which is
      not found in plant mitochondria, by interacting with the C-terminal (M)EEVD motif
      of the heat shock proteins Hsp90 and Hsp70. In this study, we show that OM64 is
      phosphorylated within its TPR domain. Using isothermal titration calorimetry it
      could be demonstrated that phosphorylation reduces the binding affinity of OM64
      to Hsp90. Moreover, in vivo expression of genes encoding different OM64 variants
      in planta revealed that phosphorylation of OM64 impairs the import efficiency of
      the mitochondrial preprotein pFAD, a subunits of the mitochondrial ATP synthase.
      In summary, our data provide significant insight into the fine-tuning mechanisms
      of mitochondrial protein import mediated by phosphorylation of the cytosolic
      exposed receptor protein OM64.

PMID- 29374545
TI  - Surgical Drains in Chronic Subdural Hematoma Surgery: From the Cheapest to the
      Most Expensive Drains.
AB  - OBJECTIVE: Among the various neurosurgical techniques currently being used in
      chronic subdural hematoma (CSDH) surgery, bur hole craniostomy is the most
      popular worldwide. Recent studies have strongly recommended that a drain be
      placed after surgical evacuation of a hematoma, and a broad spectrum of preformed
      surgical drains is widely available for this purpose. If preformed drains are
      unavailable, a surgeon-made drain can be used and various methods are available
      to develop a drain in the operating room. METHODS: Using a case report, we
      demonstrate how to develop a surgeon-made drain. Next, we retrospectively
      screened for subdural drain usage in consecutive patients undergoing bur hole
      drainage for CSDH at Adiyaman University Hospital between January 2017 and April
      2017, and data from only those patients in whom a surgeon-made drain was used
      were included for analyses. RESULTS: A 74-year-old male was operated with the
      diagnosis of CSDH. Assembly of a surgeon-made drain was explained step by step.
      Our review identified 6 unilateral and 2 bilateral cases in which 10 surgeon-made
      drains were used. Mean age of the patients was 72, and mean follow-up period was
      7 months, 23 days. No instances of infection or drain-related complications had
      been recorded. The recurrence rate was 0%, and the average drainage period was
      3.4 days. CONCLUSIONS: In case of unavailability of a preformed drain, a surgeon
      made drain can be used during CSDH surgery. Different methods are available and
      can be further diversified using various combinations of simple medical
      materials.

PMID- 29374543
TI  - Lysosomal acid lipase regulates fatty acid channeling in brown adipose tissue to
      maintain thermogenesis.
AB  - Lysosomal acid lipase (LAL) is the only known enzyme, which hydrolyzes
      cholesteryl esters and triacylglycerols in lysosomes of multiple cells and
      tissues. Here, we explored the role of LAL in brown adipose tissue (BAT). LAL
      deficient (Lal-/-) mice exhibit markedly reduced UCP1 expression in BAT, modified
      BAT morphology with accumulation of lysosomes, and mitochondrial dysfunction,
      consequently leading to regular hypothermic events in mice kept at room
      temperature. Cold exposure resulted in reduced lipid uptake into BAT, thereby
      aggravating dyslipidemia and causing life threatening hypothermia in Lal-/- mice.
      Linking LAL as a potential regulator of lipoprotein lipase activity, we found
      Angptl4 mRNA expression upregulated in BAT. Our data demonstrate that LAL is
      critical for shuttling fatty acids derived from circulating lipoproteins to BAT
      during cold exposure. We conclude that inhibited lysosomal lipid hydrolysis in
      BAT leads to impaired thermogenesis in Lal-/- mice.

PMID- 29374547
TI  - A Web Effect: Plummer-Vinson Syndrome.

PMID- 29374546
TI  - Cortical Reorganizations for Recovery from Depressive State After Spinal
      Decompression Surgery.
AB  - BACKGROUND: Depressed mood following neuronal damage not only impedes functional
      recovery but also negatively affects quality of life for many patients. Depressed
      patients with cervical myelopathy often show improvement in both mood and motor
      function after spinal decompression surgery; however, the neural mechanism
      underlying this psychological benefit from surgery remains unclear. The aim of
      this study was to clarify the brain sites that relate to alleviation of
      depression after spinal decompression surgery. METHODS: We compared brain
      activity of patients with cervical myelopathy (n = 6) with healthy participants
      (n = 5) using functional magnetic resonance imaging. We then analyzed functional
      magnetic resonance imaging data to find the brain regions that correlated with
      depression severity (n = 12; 6 preoperative patients and 6 postoperative
      patients) and compared preoperative imaging data with postoperative imaging data
      from patients. RESULTS: Spinal decompression surgery alleviated depression and
      diminished anterior cingulate cortex activity. Simultaneously, supplementary
      motor area activity, which was increased in patients with myelopathy compared
      with control subjects, was diminished after surgery. CONCLUSIONS: Traditionally,
      surgical indications for myelopathy are determined by the severity of
      sensorimotor symptoms without considering psychological symptoms. We anticipate
      our results will lead to more informed surgical decisions for cervical
      spondylosis myelopathy.

PMID- 29374548
TI  - Pirfenidone prevents radiation-induced intestinal fibrosis in rats by inhibiting
      fibroblast proliferation and differentiation and suppressing the TGF
      beta1/Smad/CTGF signaling pathway.
AB  - Radiation-induced intestinal fibrosis (RIF) is a chronic toxicity following
      radiation, and can be very difficult to treat. Pirfenidone is a promising anti
      fibrotic agent that inhibits fibrosis progression in various clinical and
      experimental studies. This study was aimed to explore whether pirfenidone could
      protect against RIF, and to evaluate the underlying mechanism. An animal model of
      RIF was induced by exposure of a single dose of 20 Gy to the pelvis. Rats were
      orally administered with pirfenidone (200, 400 md/kg/d) for 12 weeks. Primary rat
      intestinal fibroblasts were cultured to determine the effects of pirfenidone on
      TGF-beta1-induced (5 ng/ml) proliferation and transdifferentiation of
      fibroblasts. The expression of collagen I, alpha-SMA, and TGF-beta1/Smad/CTGF
      pathway proteins were analyzed by qRT-PCR and/or western blot analysis. The cell
      proliferation rate was determined by CCK-8 assay. The results indicated that
      pirfenidone significantly attenuated fibrotic lesion in irradiated intestines and
      reduced collagen deposition by inhibiting TGF-beta1/Smad/CTGF pathway in rat
      models. Moreover, in primary rat intestinal fibroblasts, pirfenidone decreased
      the up-regulation of TGF-beta1-induced collagen I and alpha-SMA by suppressing
      TGF-beta1/Smad/CTGF signaling pathway. Altogether, our findings suggested that
      pirfenidone attenuated RIF by inhibiting the proliferation and differentiation of
      intestinal fibroblasts and suppressing the TGF-beta1/Smad/CTGF signaling pathway.

PMID- 29374549
TI  - Matrine suppresses AGE-induced HAEC injury by inhibiting ROS-mediated NRLP3
      inflammasome activation.
AB  - Diabetes is characterized by a high level of advanced glycation end products
      (AGEs), which induce damage in the arterial endothelium. Matrine has been shown
      to have cardioprotective effects. This study's aim was to investigate the
      protective effects and possible molecular mechanisms of matrine in AGE-induced
      human aortic endothelial cell (HAEC) injury. Cultured HAECs were treated with
      AGEs and/or serially diluted matrine. Cell viability was evaluated by MTT assay.
      Intracellular reactive oxygen species production was determined by flow
      cytometry. The expression levels of nucleotide-binding, leucine-rich repeat, and
      pyrin-domain-containing 3 (NLRP3), adaptor molecule apoptosis-associated speck
      like protein, cleaved caspase-1 and interleukin-1beta (IL-1beta) were assessed by
      Western blotting; the concentration of IL-1beta in culture supernatants was
      determined by enzyme-linked immunosorbent assay (ELISA). In a concentration
      dependent manner, matrine co-treatment with AGEs substantially inhibited the
      reduction in cell viability and the increase in intracellular reactive oxygen
      species induced by AGEs. Co-treatment with matrine significantly inhibited the
      AGE-induced increase in NLRP3, ASC, caspase-1, p20 and IL-1beta expression in
      HAECs in a concentration-dependent manner. Moreover, the AGE-mediated increase in
      IL-1beta expression in cell culture supernatants was also reduced by co-treatment
      with matrine in a concentration-dependent manner. AGEs induced HAEC injury by
      inducing reactive oxygen species -mediated NLRP3 inflammasome activation. Matrine
      recovered HAEC viability by inhibiting reactive oxygen species -mediated NLRP3
      inflammasome activation.

PMID- 29374550
TI  - A new open-source tool for measuring 3D osteocyte lacunar geometries from
      confocal laser scanning microscopy reveals age-related changes to lacunar size
      and shape in cortical mouse bone.
AB  - Osteocytes can participate in systemic mineral homeostasis through perilacunar
      maintenance and remodeling, where changes to osteocyte lacunar morphology may
      affect bone structural integrity, tissue strains, and osteocyte
      mechanosensitivity. Though aging is associated with both decreased bone quality
      and altered mineral metabolism, it is not known if osteocyte lacunae undergo age
      related changes in geometry. In order to survey lacunar changes with age, we
      developed an open-source program whereby 3D osteocyte lacunae are automatically
      segmented and then subsequently reconstructed from confocal laser scanning
      microscopy (CLSM) depth stacks for quantitative analysis of geometry and
      orientation. This approach takes advantage of the availability and speed of CLSM
      while avoiding time-consuming and bias-prone manual segmentation. Unlike
      conventional approaches used to quantify osteocyte lacunar morphology, CLSM
      enables facile analysis in three-dimensions with clear identification of
      osteocyte lacunae. We report that 3D osteocyte lacunae measured by CLSM become
      smaller, more spherical, more oblate, more spatially disorganized, and more
      sparsely populated with increased age in C57Bl/6 mouse cortical bone in groups
      spanning 6-24 months old. Critically, these age-related changes are in large part
      not observed in 2D analyses from the same samples. These results (1) demonstrate
      proof-of-concept of an efficient method to quantitatively assess osteocyte
      lacunae in 3D for application to a wide range of studies and (2) motivate further
      inquiry into how changes to osteocyte lacunar geometries and perilacunar material
      contribute to diminished bone quality in aging.

PMID- 29374551
TI  - Retinal conduction speed analysis reveals different origins of the P50 and N95
      components of the (multifocal) pattern electroretinogram.
AB  - The pattern electroretinogram (PERG), an indicator of retinal ganglion cell (RGC)
      function, comprises a P50 and an N95 component. We addressed the question of
      whether the N95 originates, like the P50, from the RGC bodies or from the change
      of axon orientation at the optic nerve head (ONH). Thus, we recorded multifocal
      PERGs for 36 retinal locations in 21 participants. Second-order kernel responses
      were analyzed for the dependence of peak time topography on retinal fiber lengths
      to the ONH separately for the positive and negative excursions. We found that
      peak times were longer for macular [P1 (P50-like): 50 ms; N2 (N95-like): 76)]
      than for peripheral responses [P1: 43; N2: 66]. For the N2 another factor was
      necessary to explain the variability: The time difference (deltaT: N2 minus P1)
      was found to be proportional to fiber length from ganglion cell body to the ONH.
      We calculated retinal fiber length using an analytical function by Jansonius et
      al. (2009, 2012) and found that a linear model with factors eccentricity and
      fiber length explained 82% of the total N2 time variance (p"0.001). The
      conduction speeds of the retinal axons were estimated from deltaT to range from
      0.5 to 3.0 m/s for parafovea and periphery, respectively. The dependence of
      deltaT on the distance from ganglion cell body to the ONH suggests that the N2
      originates at the ONH rather than at the ganglion cell body. While the multifocal
      N2 peaks earlier (~76 ms) than the non-multifocal PERG-N95 (~95 ms),
      considerations of high-pass filtering and frequency dependence of the mfPERG-N2
      suggest that the source separation (P50 = ganglion cell body vs. N95 = ONH) also
      holds for the non-multifocal PERG.

PMID- 29374552
TI  - Spatial attention modulates the temporal sequence of hemispheric asymmetry in
      configural and featural face processing.
AB  - Face recognition requires both configural and featural processing. Configural
      face processing is more dependent on the right hemisphere, whereas featural face
      processing is more dependent on the left hemisphere. The ERP components sensitive
      to configural and featural face processing were found on P1 and P2, respectively.
      However, whether lateralized processing is independent of or interacts with the
      temporal sequence of configural and featural face processing is unclear. To
      prevent potentially confounding physical stimuli differences between configural
      and featural face processing from affecting the ERP components, a spatial
      attention paradigm was employed in which the participants were instructed to
      attend to the face location (the attended face condition) or the house location
      (the unattended face condition). The interaction effect of attention, face
      processing type and hemisphere on the P1 and P2 components indicates that the
      different mechanisms of configural and featural face processing are a function of
      spatial attention. Specifically, under the attended face condition, the posterior
      P1 (approximately 100 ms) for configural face processing was larger than that for
      featural face processing in the right hemisphere, whereas the P2 (approximately
      220 ms) for featural face processing was larger than that for configural face
      processing in the left hemisphere. In contrast, under the unattended face
      condition, the P1 for featural face processing was larger than that for
      configural face processing in the left hemisphere, whereas the P2 for configural
      face processing was larger than that for featural face processing in the right
      hemisphere. Therefore, configural and featural processing involve different
      neural mechanisms, and more importantly, the time course of hemispheric asymmetry
      in configural and featural face processing is differentially modulated by spatial
      attention.

PMID- 29374553
TI  - Optimal visuo-vestibular integration for self-motion perception in patients with
      unilateral vestibular loss.
AB  - Unilateral vestibular loss (UVL) is accompanied by deficits in processing of
      visual and vestibular self-motion cues. The present study examined whether
      multisensory integration of these two types of information is, nevertheless,
      intact in such patients. Patients were seated on a rotating platform with a
      screen simulating 3D rotation in front of them and asked to judge the relative
      magnitude of two successive rotations in the yaw plane in three conditions:
      vestibular stimulation, visual stimulation and bimodal stimulation (congruent
      stimuli from both modalities together). Similar to findings in healthy controls,
      UVL patients exhibited optimal multisensory integration during both ipsi- and
      contralesional rotations. The benefit of multisensory integration was more
      pronounced on the ipsilesional side. These results show that visuo-vestibular
      integration for passive self-motion is automatic and suggests that it functions
      without additional cognitive mechanisms, unlike more complex multisensory tasks
      such as postural control and spatial navigation, previously shown to be impaired
      in UVL patients.

PMID- 29374554
TI  - Individual variation in ACTH-induced cortisol levels in females of a livebearing
      fish at different gestational stages.
AB  - Individuals vary in their baseline levels of stress hormones (predictive
      homeostasis) and in their stress responses (reactive homeostasis). Variation in
      normal reactive scope, both predictive and reactive homeostasis, may be important
      for understanding how endocrine traits respond to selection. Reactive homeostasis
      is the increase in glucocorticoid (GCs) hormones above baseline. Individuals at
      different life history stages, such as gestation in females, may show variation
      in normal reactive scope. We performed an adrenocorticotropic hormone (ACTH)
      challenge and measured changes in circulating GCs to estimate the reactive scope
      of female sailfin mollies (Poecilia latipinna) at different gestational states.
      We measured cortisol, primary GC in teleost fishes, to obtain baseline release
      rates prior to injection with either ACTH or saline control. Using water-borne
      hormones, we measured cortisol release rates at four time intervals post
      injection. Females were then sacrificed to determine the developmental stage of
      embryos, if present, and the number of developing embryos or mature ova. We found
      that ACTH-injected females had significant increases in cortisol releases rates,
      whereas cortisol release rates of control females did not change during the 4 h
      post-injection period. We found high repeatability in predictive homeostasis of
      cortisol and moderate repeatability in reactive homeostasis and a phenotypic
      correlation between predictive and reactive homeostasis. Gestational state did
      not affect female predictive or reactive homeostasis. We applied the reactive
      scope model to P. latipinna and gained a further understanding of how among- and
      within-individual variation in both predictive and reactive homeostasis are
      partitioned and how these traits vary under certain life-history conditions.

PMID- 29374555
TI  - Performance evaluation of the new measurement channels on the automated Sysmex XN
      9000 hematology analyzer.
AB  - BACKGROUND: The automated Sysmex XN-9000 hematology system has been designed to
      meet the throughput and efficiency requirements of high volume laboratories with
      predominantly abnormal samples. New measurement channels have been introduced
      namely the white cell nucleated (WNR), white cell differential (WDF), white cell
      precursor (WPC) and fluorescent platelet (PLT-F) channels. METHODS: The
      performance of the new measurement channels was evaluated with regards to
      precision, accuracy, linearity, carryover, throughput and stability. 275 slides
      were assessed for morphology flagging. Adult and pediatric samples with normal
      and abnormal hematology profiles were included. RESULTS: The XN-9000 demonstrated
      acceptable imprecision, good linearity for high and low ranges and no carryover.
      The full blood count and reticulocyte on the XN-9000 correlated well with the
      reference ADVIA(2)120. The PLT-F (127+/-84*109/l) compared with the optical
      platelet count (131+/-76*109/l) (r=0.97) and the imprecision was <4% on
      thrombocytopenic samples. The low white blood cell (WBC) mode reported accurate
      differentials for samples with a WBC count<0.5*109/l (r=0.93). The nucleated red
      blood cell count from the WNR (1.22+/-3.96%) showed an excellent correlation with
      the manual method (1.12+/-4.79%) (r=0.99). The WPC channel showed 100%
      sensitivity for the detection of blasts and abnormal lymphocytes. Further, the
      WPC correctly suppressed the initial blast/abnormal lymphocyte flag in 34% of the
      reflexed samples. CONCLUSION: The XN-9000 showed enhanced analytical performance
      and workflow efficiency for a wide range of patient samples which can be
      attributed to the incorporation of new measurement channels.

PMID- 29374556
TI  - CCL5 deficiency rescues pulmonary vascular dysfunction, and reverses pulmonary
      hypertension via caveolin-1-dependent BMPR2 activation.
AB  - Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder
      characterized by pulmonary arterial remodeling mainly due to excess cellular
      proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells
      (PASMCs). Reduced bone morphogenetic protein receptor 2 (BMPR2) expression in
      patients with PAH impairs pulmonary arterial endothelial cells (PAECs) function.
      This can adversely affect PAEC survival and promote PASMCs proliferation. We
      hypothesized that interventions to normalize the expression of genes that are
      targets of the BMPR2 signaling could restore PAECs function and prevent or
      reverse PAH. Here we characterized for the first time, in human PAECs, chemokine
      (C-C motif) ligand 5 (CCL5/RANTES) deficiency restore BMP-mediated PAECs
      function. In the cell culture experiments, we found that CCL5 deficiency
      increased apoptosis and tube formation of PAECs, but suppressed proliferation and
      migration of PASMCs. Silencing CCL5 expression in PAH PAECs restored bone
      morphogenetic protein (BMP) signaling responses and promoted phosphorylation of
      SMADs and transcription of ID genes. Moreover, CCL5 deficiency inhibited
      angiogenesis by increasing pSMAD-dependent and-independent BMPR2 signaling. This
      was linked mechanistically to enhanced interaction of BMPR2 with caveolin-1 via
      CCL5 deficiency-mediated stabilization of endothelial surface caveolin-1.
      Consistent with these functions, deletion of CCL5 significantly attenuated
      development of Sugen5416/hypoxia-induced PAH by restoring BMPR2 signaling in
      mice. Taken together, our findings suggest that CCL5 deficiency could reverse
      obliterative changes in pulmonary arteries via caveolin-1-dependent amplification
      of BMPR2 signaling. Our results shed light on better understanding of the disease
      pathobiology and provide a possible novel target for the treatment of PAH.

PMID- 29374557
TI  - Molecular Paths Linking Metabolic Diseases, Gut Microbiota Dysbiosis and
      Enterobacteria Infections.
AB  - Alterations of both ecology and functions of gut microbiota are conspicuous
      traits of several inflammatory pathologies, notably metabolic diseases such as
      obesity and type 2 diabetes. Moreover, the proliferation of enterobacteria,
      subdominant members of the intestinal microbial ecosystem, has been shown to be
      favored by Western diet, the strongest inducer of both metabolic diseases and gut
      microbiota dysbiosis. The inner interdependence between the host and the gut
      microbiota is based on a plethora of molecular mechanisms by which host and
      intestinal microbes modify each other. Among these mechanisms are as follows: (i)
      the well-known metabolic impact of short chain fatty acids, produced by microbial
      fermentation of complex carbohydrates from plants; (ii) a mutual modulation of
      miRNAs expression, both on the eukaryotic (host) and prokaryotic (gut microbes)
      side; (iii) the production by enterobacteria of virulence factors such as the
      genotoxin colibactin, shown to alter the integrity of host genome and induce a
      senescence-like phenotype in vitro; (iv) the microbial excretion of outer
      membrane vesicles, which, in addition to other functions, may act as a carrier
      for multiple molecules such as toxins to be delivered to target cells. In this
      review, I describe the major molecular mechanisms by which gut microbes exert
      their metabolic impact at a multi-organ level (the gut barrier being in the front
      line) and support the emerging triad of metabolic diseases, gut microbiota
      dysbiosis and enterobacteria infections.

PMID- 29374558
TI  - Cortactin recruits FMNL2 to promote actin polymerization and endosome motility in
      invadopodia formation.
AB  - Recently, invadopodia have been increasingly recognized as important drivers of
      local invasion and metastasis. Cortactin, as an actin-binding protein, is closely
      associated with invadopodia through interacting with proteins. Formin-like 2
      (FMNL2), a member of diaphanous-related formins which act as nucleation factors,
      plays an important role in tumor progression. But whether cortactin can interact
      with FMNL2 to promote invadopodia formation and the role of FMNL2 in invadopodia
      formation are still unknown. Here we found that cortactin directly bound to FMNL2
      and elevated the activities of actin polymerization and recycling endosome
      motility. FMNL2 was necessary for invadopodia formation and function in CRC
      cells. The interaction of cortactin and FMNL2 could further promote the
      invadopodia formation and matrix degradation. The stimulation of EGF/cdc42
      enhanced the combination of cortactin and FMNL2 to intensify the numbers of
      invadopodia and the degrees of matrix degradation. In vivo, induction of
      invadopodia formation via cortactin is essential for the ability of FMNL2 to
      promote CRC metastasis. Furthermore, up-regulations of FMNL2 and cortactin were
      highly linked in CRC tissues. Collectively, our work demonstrates a brand-new
      mechanism of cortacin and FMNL2 at invadopodia in CRC.

PMID- 29374559
TI  - FNDC5 attenuates adipose tissue inflammation and insulin resistance via AMPK
      mediated macrophage polarization in obesity.
AB  - BACKGROUND: Obesity-induced chronic inflammation is critical in the pathogenesis
      of insulin resistance, and the recruitment and proinflammatory activation of
      adipose tissue macrophages (ATMs) is important for the development of this
      process. Here, we examined the effects of fibronectin type III domain-containing
      5 (FNDC5) on inflammation and insulin resistance in high-fat diet-induced obese
      mice. MATERIALS AND METHODS: Male wild-type (WT) and FNDC5-/- mice were fed with
      standard chow (Ctrl) or high fat diet (HFD) for 20 weeks to induce obesity and
      insulin resistance. Firstly, effects of FNDC5 gene deletion on obesity, insulin
      resistance, macrophage accumulation and polarization and adipose tissue
      inflammation were determined in mice. Secondly, the macrophage polarity shift was
      further examined with flow cytometry in isolated stromal vascular fraction (SVF).
      Thirdly, the effects of exogenous FNDC5 on lipopolysaccharide (LPS)-induced
      macrophage polarization, inflammation and the underlying signaling mechanism were
      investigated in RAW264.7 macrophages and primary mouse peritoneal cavity
      macrophages (PMs). Finally, the therapeutic effects of FNDC5 overexpression were
      examined in HFD-induced obese WT and FNDC5-/- mice. RESULTS: FNDC5 gene deletion
      aggravated obesity, insulin resistance, fat accumulation and inflammation
      accompanied with enhanced AMPK inhibition, macrophages recruitment and M1
      polarization in mice fed with HFD. Exogenous FNDC5 inhibited LPS-induced M1
      macrophage polarization and inflammatory cytokine production via AMPK
      phosphorylation in both RAW264.7 macrophages and PMs. FNDC5 overexpression
      attenuated insulin resistance, AMPK inhibition, M1 macrophage polarization and
      inflammatory cytokine production in adipose tissue of obese WT and FNDC5-/- mice.
      CONCLUSIONS: FNDC5 attenuates adipose tissue inflammation and insulin resistance
      via AMPK-mediated macrophage polarization in HFD-induced obesity. FNDC5 plays
      several beneficial roles in obesity and may be used as a therapeutic regimen for
      preventing inflammation and insulin resistance in obesity and diabetes.

PMID- 29374560
TI  - Cellular and functional biomarkers of clinical transplant tolerance.
AB  - Development of tolerance protocols requires assays or biomarkers that distinguish
      tolerant recipients from non-tolerant ones to be established. In addition, a
      thorough understanding of the plausible mechanisms associated with clinical
      transplant tolerance is necessary to take the field forward. Unlike the majority
      of molecular signature analyses utilized by others, the emphasis of this article
      is on the cellular and functional biomarkers of induced transplant tolerance.
      Immunity to an organ transplant is very complex, comprised of two broad
      categories - innate and acquired or adaptive immune responses. Innate immunity
      can be avoided by eliminating or preventing ischemic injuries to the donor organ
      and tolerance at the level of adaptive immunity can be induced by infusions of a
      number of cellular products. Since adaptive immune response consists of
      inflammatory hypersensitivity, cellular (cytotoxic and helper) and humoral
      aspects, all these need to be measured, and the recipients who demonstrate donor
      specific unresponsiveness in all can be considered tolerant or candidates for
      immunosuppression minimization and/or withdrawal. The mechanisms by which these
      agents bring about transplant tolerance include regulation, anergy, exhaustion,
      senescence and deletion of the recipient immune cells. Another proven mechanism
      of tolerance is full or mixed donor chimerism. However, it should be cautioned
      that non-deletional tolerance can be reversed.

PMID- 29374561
TI  - Current status of muscarinic M1 and M4 receptors as drug targets for
      neurodegenerative diseases.
AB  - The cholinergic signalling system has been an attractive pathway to seek targets
      for modulation of arousal, cognition, and attention which are compromised in
      neurodegenerative and neuropsychiatric diseases. The acetylcholine muscarinic
      receptor M1 and M4 subtypes which are highly expressed in the central nervous
      system, in cortex, hippocampus and striatum, key areas of cognitive and
      neuropsychiatric control, have received particular attention. Historical
      muscarinic drug development yielded first generation agonists with modest
      selectivity for these two receptor targets over M2 and M3 receptors, the major
      peripheral sub-types hypothesised to underlie the dose-limiting clinical side
      effects. More recent compound screening and medicinal chemistry optimization of
      orthosteric and allosteric agonists, and positive allosteric modulators binding
      to sites distinct from the highly homologous acetylcholine binding pocket have
      yielded a collection of highly selective tool compounds for preclinical
      validation studies. Several M1 selective ligands have progressed to early
      clinical development and in time will hopefully lead to useful therapeutics for
      treating symptoms of Alzheimer's disease and related disorders. This article is
      part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'.

PMID- 29374563
TI  - Does the use of melatonin overcome drug resistance in cancer chemotherapy?
AB  - Our knowledge regarding the implications of melatonin in the therapy of numerous
      medical conditions, including cancer is constantly expanding. Melatonin can
      variably affect cancer pathology via targeting several key aspects of any
      neoplastic condition, including the very onset of carcinogenesis as well as tumor
      growth, differentiation, and dissemination. Numerous studies have examined the
      effects of melatonin in the context of various cancers reporting the enhanced
      efficacy of chemo/radiotherapy in combination with this compound. Reduced
      sensitivity and also resistance of cancer cells to antineoplastic agents are
      common events which might arise as a result of genomic instability of the
      malignant cells. Genetic mutations provide numerous mechanisms for these cells to
      resist cytotoxic therapies. Melatonin, due to its pleitropic effects, is able to
      correct these alterations in favour of sensitization to antineoplastic agents as
      evident by increased response to treatment via modulating the expression and
      phosphorylation status of drug targets, the reduced clearance of drugs by
      affecting their metabolism and transport within the body, decreased survival of
      malignant cells via altering DNA repair and telomerase activity, and enhanced
      responsiveness to cell death-associated mechanisms such as apoptosis and
      autophagy. These effects are presumably governed by melatonin's interventions in
      the main signal transduction pathways such as Akt and MAPK, independent of its
      antioxidant properties. Possessing such a signaling altering nature, melatonin
      can considerably affect the drug-resistance mechanisms employed by the malignant
      cells in breast, lung, hepatic, and colon cancers as well as different types of
      leukemia which are the subject of the current review.

PMID- 29374562
TI  - Food-induced reinforcement is abrogated by the genetic deletion of the MT1 or MT2
      melatonin receptor in C3H/HeN mice.
AB  - Palatable food is known for its ability to enhance reinforcing responses. Studies
      have suggested a circadian variation in both drug and natural reinforcement, with
      each following its own time course. The goal of this study was to determine the
      role of the MT1 and MT2 melatonin receptors in palatable snack food-induced
      reinforcement, as measured by the conditioned place preference (CPP) paradigm
      during the light and dark phases. C3H/HeN wild-type mice were trained for snack
      food-induced CPP at either ZT 6 - 8 (ZT: Zeitgeber time; ZT 0 = lights on), when
      endogenous melatonin levels are low, or ZT 19 - 21, when melatonin levels are
      high. These time points also correspond to the high and low points for expression
      of the circadian gene Period1, respectively. The amount of snack food (chow,
      Cheetos(r), Froot Loops(r) and Oreos(r)) consumed was of similar magnitude at
      both times, however only C3H/HeN mice conditioned to snack food at ZT 6 - 8
      developed a place preference. C3H/HeN mice with a genetic deletion of either the
      MT1 (MT1KO) or MT2 (MT2KO) receptor tested at ZT 6 - 8 did not develop a place
      preference for snack food. Although the MT2KO mice showed a similar amount of
      snack food consumed when compared to wild-type mice, the MT1KO mice consumed
      significantly less than either genotype. We conclude that in our mouse model
      snack food-induced CPP is dependent on time of day and the presence of the MT1 or
      MT2 receptors, suggesting a role for melatonin and its receptors in snack food
      induced reinforcement.

PMID- 29374564
TI  - Structural investigation of cellobiose dehydrogenase IIA: Insights from small
      angle scattering into intra- and intermolecular electron transfer mechanisms.
AB  - BACKGROUND: Cellobiose dehydrogenases have gained interest due to their potential
      applications in sectors from biofuel production to biomedical devices. The CDHIIA
      variant is comprised of a cytochrome domain (CYT), a dehydrogenase domain (DH),
      and a carbohydrate-binding module (CBM) that are connected by two flexible
      linkers. Upon cellobiose oxidation at the DH, intramolecular electron transfer
      (IaET) occurs from the DH to the CYT. In vivo, CDHIIA CYT subsequently performs
      intermolecular electron transfer (IeET) to a lytic polysaccharide monooxygenase
      (LPMO). The relevant solution-state CDH domain conformations for IaET and IeET
      have not been fully characterized. METHODS: Small-angle X-ray and neutron
      scattering measurements of oxidized CDHIIA from Myriococcum thermophilum and
      Neurospora crassa were performed to investigate the structural landscape explored
      in solution by MtCDHIIA and NcCDHIIA in response to cations, pH, and the presence
      of an electron acceptor, LPMO9D from N. crassa. RESULTS: The scattering data
      complemented by modeling show that, under oxidizing conditions, MtCDHIIA
      undergoes global conformational rearrangement in the presence of Ca2+. Oxidized
      NcCDHIIA exhibits conformational changes upon pH variation and, in the presence
      of NcLPMO9D, primarily adopts a compact conformation. CONCLUSIONS: These results
      demonstrate different conformational responses of oxidized MtCDHIIA and NcCDHIIA
      to changes in environment. The results also reveal a shift in the oxidized
      NcCDHIIA conformational landscape toward interdomain compaction upon co
      incubation with NcLPMO9D. GENERAL SIGNIFICANCE: The present study is the first
      report on the structural landscapes explored in solution by oxidized cellobiose
      dehydrogenases under various cation concentrations, pH conditions and in the
      presence of an electron-accepting LPMO.

PMID- 29374565
TI  - Effects of extraction methods on the rheological properties of polysaccharides
      from onion (Allium cepa L.).
AB  - In this work we described the rheological properties of polysaccharides (HBSS,
      CHSS, DASS, CASS) sequentially extracted from onion (Allium cepa L.). Four onion
      polysaccharides (ACLPs) solutions resulted into significant differences on their
      rheological properties. ACLPs solutions showed non-Newtonian shear-thinning
      behavior over the range of 0.5-2.5%. At concentration of 1%, the apparent
      viscosity of CHSS was observed to be the highest. The apparent viscosity of ACLPs
      solutions decreased with the acidic pH (4.0) or alkaline pH (10.0) which was
      further declined at higher temperature (90  degrees C). After the addition of
      various salts, ACLPs had apparent differences on apparent viscosity. The G'
      (storage modulus) and G" (loss modulus) of ACLP solutions were increased with
      increasing oscillation frequency. Moreover, the crossover value of oscillation
      frequency gradually decreased with increasing concentration of ACLPs. Our results
      exhibited that among the ACLPs, CHSS can be used as supplements in the food
      industry as thickening agent, gelling agent and stabilizer.

PMID- 29374566
TI  - High-performance biodegradable polylactide composites fabricated using a novel
      plasticizer and functionalized eggshell powder.
AB  - A novel polyester poly(diethylene glycol succinate) (PDEGS) was synthesized and
      evaluated as a plasticizer for polylactide (PLA) in this study. Meanwhile, an
      effective sustainable filler, functionalized eggshell powder (FES) with a surface
      layer of calcium phenyphosphonate was also prepared. Then, PLA biocomposites were
      prepared from FES and PDEGS using a facile melt blending process. The addition of
      15 wt% PDEGS as plasticizer showed good miscibility with PLA macromolecules and
      increased the chain mobility of PLA. The crystallization kinetics of PLA
      composites revealed that the highly effective nucleating FES significantly
      improved the crystallization ability of PLA at both of non-isothermal and
      isothermal conditions. In addition, the effective plasticizer and well-dispersed
      FES increased the elongation at break from 6% of pure PLA to over 200% for all of
      the plasticized PLA composites. These biodegradable PLA biocomposites, coupled
      with excellent crystallization ability and tunable mechanical properties,
      demonstrate their potential as alternatives to traditional commodity plastics.

PMID- 29374567
TI  - Cannabis Use, Lung Cancer, and Related Issues.
AB  - The cannabis plant and its derivatives have been exploited for centuries for
      recreational and medicinal purposes, with millions of regular users around the
      world. The recreational use of cannabis is reflective of its neuropsychiatric
      effects, such as anxiolysis and euphoria. However, cannabis appears to have an
      emerging therapeutic role, especially in chronic disease and as an adjunct to
      cancer treatment. Increasing evidence supports cannabis in the management of
      chemotherapy-induced nausea and vomiting (CINV) and for pain management; however,
      studies are limited, particularly by difficulties associated with standardized
      dosing estimates and inability to accurately assess biologic activities of
      compounds in cannabis and derivative products. Smoking cannabis has not been
      proved to be a risk factor in the development of lung cancer, but the data are
      limited by small studies, misclassification due to self-reporting of use, small
      numbers of heavy cannabis smokers, and confounding of the risk associated with
      known causative agents for lung cancer (such as parallel chronic tobacco use).
      Cannabis and its biologically effective derivatives warrant additional research,
      ideally, controlled trials in which the cannabidiol and the delta-9
      tetrahydrocabinol strength and use are controlled and documented.

PMID- 29374569
TI  - Diketopiperazines and 2H-pyran-2-ones with antioxidant activity from the rice
      fermented with Aspergillus luchuensis.
AB  - Aspergillus luchuensis is widely used as a starter of saccharification in the
      koji industry, but no secondary metabolites have been reported from this fungus.
      Herein, we report the isolation and identification of four new diketopiperazine
      derivatives (1-4), one new methyl 4-(3-acetyl-2, 6-dihydroxyphenyl)-2
      methoxybutanoate (5), and six known compounds (6-11) from the rice koji of A.
      luchuensis. The structures of 1-5 were determined by extensive spectral analysis
      including 1D and 2D NMR, HRESIMS, and CD, and ECD calculation. In antioxidant
      assays, compound 10 displayed moderate DPPH scavenging activity with an EC50
      value of 60.8MUM; compounds 1-4, 10 and 11 showed reducing ability with EC50
      values ranging from 8.73 to 176.39MUM. Compounds 1-11 showed no cytotoxicity
      against cell lines A549, K562, ASPC, and H460 at 200MUM. Our current reports
      support the safety of A. luchuensis in food chemistry and confirm this fungus to
      be a new source of natural antioxidants.

PMID- 29374568
TI  - Diverse functions of protein tyrosine phosphatase sigma in the nervous and immune
      systems.
AB  - Tyrosine phosphorylation is a common means of regulating protein functions and
      signal transduction in multiple cells. Protein tyrosine phosphatases (PTPs) are a
      large family of signaling enzymes that remove phosphate groups from tyrosine
      residues of target proteins and change their functions. Among them, receptor-type
      PTPs (RPTPs) exhibit a distinct spatial pattern of expression and play essential
      roles in regulating neurite outgrowth, axon guidance, and synaptic organization
      in developmental nervous system. Some RPTPs function as essential receptors for
      chondroitin sulfate proteoglycans that inhibit axon regeneration following CNS
      injury. Interestingly, certain RPTPs are also important to regulate functions of
      immune cells and development of autoimmune diseases. PTPsigma, a RPTP in the LAR
      subfamily, is expressed in various immune cells and regulates their
      differentiation, production of various cytokines and immune responses. In this
      review, we highlight the physiological and pathological significance of PTPsigma
      and related molecules in both nervous and immune systems.

PMID- 29374570
TI  - Ethylnaphthoquinone derivatives as inhibitors of indoleamine-2, 3-dioxygenase
      from the mangrove endophytic fungus Neofusicoccum austral SYSU-SKS024.
AB  - Bioassay-guided fractionation of the dichloromethane extract of the fungus
      Neofusicoccum austral SYSU-SKS024 led to the isolation of three new
      ethylnaphthoquinone derivatives, neofusnaphthoquinone A (1), 6-(1-methoxylethy1)
      2,7-dimethoxyjuglone (2), (3R,4R)-3-methoxyl-botryosphaerone D (6), together with
      six known analogs (3-5 and 7-9). Their structures were elucidated by
      spectroscopic analysis and single crystal X-ray diffraction analysis.
      Neofusnaphthoquinone A (1) is the third example of the unsymmetrical
      naphthoquinone dimer, which is rarely found in natural source. All of the
      isolates were evaluated for their indoleamine 2, 3-dioxygenase (IDO) inhibitory
      activity, compounds 1-6 showed in vitro inhibitory effects against IDO with IC50
      values ranging from 0.11 to 10.92MUM. This is the first time naphthoquinone dimer
      (1), as a novel carbon skeleton possessing IDO inhibitory activity, was reported.

PMID- 29374571
TI  - Predicting skin sensitizers with confidence - Using conformal prediction to
      determine applicability domain of GARD.
AB  - GARD - Genomic Allergen Rapid Detection is a cell based alternative to animal
      testing for identification of skin sensitizers. The assay is based on a biomarker
      signature comprising 200 genes measured in an in vitro model of dendritic cells
      following chemical stimulations, and consistently reports predictive performances
      ~90% for classification of external test sets. Within the field of in vitro skin
      sensitization testing, definition of applicability domain is often neglected by
      test developers, and assays are often considered applicable across the entire
      chemical space. This study complements previous assessments of model performance
      with an estimate of confidence in individual classifications, as well as a
      statistically valid determination of the applicability domain for the GARD assay.
      Conformal prediction was implemented into current GARD protocols, and a large
      external test dataset (n = 70) was classified at a confidence level of 85%, to
      generate a valid model with a balanced accuracy of 88%, with none of the tested
      chemical reactivity domains identified as outside the applicability domain of the
      assay. In conclusion, results presented in this study complement previously
      reported predictive performances of GARD with a statistically valid assessment of
      uncertainty in each individual prediction, thus allowing for classification of
      skin sensitizers with confidence.

PMID- 29374572
TI  - Increased GATA-3 and T-bet expression in eosinophilic esophagitis versus
      gastroesophageal reflux disease.

PMID- 29374573
TI  - Role of local CpG DNA methylation in mediating the 17q21 asthma susceptibility
      gasdermin B (GSDMB)/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3)
      expression quantitative trait locus.

PMID- 29374574
TI  - Gabapentin reduces haloperidol-induced vacuous chewing movements in mice.
AB  - Tardive dyskinesia (TD) is a common adverse effect observed in patients with long
      term use of typical antipsychotic medications. A vacuous chewing movement (VCM)
      model induced by haloperidol has been used to study these abnormalities in
      experimental animals. The cause of TD and its treatment remain unknown, but
      several lines of evidence suggest that dopamine receptor supersensitivity and
      gamma-aminobutyric acid (GABA) insufficiency play important roles in the
      development of TD. This study investigated the effects of treatment with the GABA
      mimetic drug gabapentin on the development of haloperidol-induced VCMs. Male mice
      received vehicle, haloperidol (1.5 mg/kg), or gabapentin (GBP, 100 mg/kg)
      intraperitoneally during 28 consecutive days. Quantification of VCMs was
      performed before treatment (baseline) and on day 28, and an open-field test was
      also conducted on the 28th day of treatment. The administration of gabapentin
      prevented the manifestation of haloperidol-induced VCMs. Treatment with
      haloperidol alone reduced the locomotor activity in the open-field test that was
      prevented by co-treatment with gabapentin. We did not find any differences among
      the groups nor in the tyrosine hydroxylase (TH) or glutamic acid decarboxylase
      (GAD) immunoreactivity or monoamine levels in the striatum of mice. These results
      suggest that treatment with gabapentin, an analog of GABA, can attenuate the VCMs
      induced by acute haloperidol treatment in mice without alterations in monoamine
      levels, TH, or GAD67 immunoreactivity in the striatum.

PMID- 29374575
TI  - The effects of hypoxia on hunger perceptions, appetite-related hormone
      concentrations and energy intake: A systematic review and meta-analysis.
AB  - Exposure to hypoxia appears to depress appetite and energy intake, however the
      mechanisms are not fully understood. The aim of this review was to determine the
      magnitude of changes in hunger and energy intake in hypoxic compared with
      normoxic environments, and establish any alterations in appetite-related hormone
      concentrations. PubMed and The Cochrane Library as well as MEDLINE, SPORTDiscus,
      PsycINFO and CINAHL, via EBSCOhost, were searched through 1st April 2017 for
      studies that evaluated hunger, energy intake and/or appetite-related hormones in
      normoxia and during hypoxic exposure in a within-measures design. A total of 28
      studies (comprising 54 fasted and 22 postprandial comparisons) were included. A
      random-effects meta-analysis was performed to establish standardised mean
      difference (SMD) with 95% confidence intervals. Hypoxic exposure resulted in a
      trivial but significant decrease in postprandial hunger scores (SMD: -0.15, 95%
      CI: -0.29 to -0.01; n = 14; p = 0.043) and a moderate decrease in energy intake
      (SMD: -0.50, 95% CI: -0.85 to -0.15; n = 8; p = 0.006). Hypoxic exposure resulted
      in a decrease (albeit trivial) in postprandial acylated ghrelin concentrations
      (SMD: -0.16, 95% CI: -0.25 to -0.08; n = 7; p < 0.0005), and a moderate increase
      in fasted insulin concentrations (SMD: 0.41, 95% CI: 0.17 to 0.65; n = 34; p =
      0.001). Meta-regression revealed a decrease in postprandial acylated ghrelin
      concentrations (p = 0.010) and an increase in fasted insulin concentrations (p =
      0.020) as hypoxic severity increased. Hypoxic exposure reduces hunger and energy
      intake, which may be mediated by decreased circulating concentrations of acylated
      ghrelin and elevated insulin concentrations. PROSPERO registration number:
      CRD42015017231.

PMID- 29374576
TI  - Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan
      production.
AB  - The tightly regulated biosynthesis and catabolism of the glycosaminoglycan
      hyaluronan, as well as its role in organizing tissues and cell signaling, is
      crucial for the homeostasis of tissues. Overexpression of hyaluronan plays
      pivotal roles in inflammation and cancer, and markedly high serum and tissue
      levels of hyaluronan are noted under such pathological conditions. This review
      focuses on the complexity of the regulation at transcriptional and
      posttranslational level of hyaluronan synthetic enzymes, and the outcome of their
      aberrant expression and accumulation of hyaluronan in clinical conditions, such
      as systemic B-cell cancers, aggressive breast carcinomas, metabolic diseases and
      virus infection.

PMID- 29374577
TI  - Evaluation of linezolid or trimethoprim/sulfamethoxazole in combination with
      rifampicin as alternative oral treatments based on an in vitro pharmacodynamic
      model of staphylococcal biofilm.
AB  - Combinations of linezolid (LZD) or trimethoprim/sulfamethoxazole (SXT) plus
      rifampicin (RIF) are alternative oral treatments for staphylococcal prosthetic
      joint infections (PJIs) when fluoroquinolones are not possible to use, but there
      is limited evidence regarding their activity. This study evaluated the efficacy
      of LZD and SXT, alone and in combination with RIF, against Staphylococcus aureus
      in an in vitro pharmacokinetic/pharmacodynamic biofilm model. Using the CDC
      Biofilm Reactor(r) system, simulated regimens of LZD (600 mg every 12 h), SXT
      (160/800 mg every 8 h) and levofloxacin (LVX) (750 mg/day), alone and in
      combination with RIF (600 mg/day), were evaluated against one methicillin
      susceptible S. aureus (MSSA) and one methicillin-resistant S. aureus (MRSA)
      strain. Antibiotic efficacy was evaluated by the decrease in planktonic bacterial
      counts from medium and biofilm-embedded bacteria from coupons over 56 h.
      Resistant strains were screened. In both strains, SXT alone was ineffective and
      LZD presented low activity, but no resistance emerged. Combinations with RIF
      significantly increased the antibiofilm efficacy against MSSA (Deltalog CFU/mL
      56h-0h: SXT + RIF, -2.9 and LZD + RIF, -3.1), but RIF-resistant strains appeared
      with SXT + RIF. Against MRSA, LZD + RIF (-3.1) protected against the emergence of
      resistance and was more effective than SXT + RIF (-0.6; P <0.05), in which RIF
      resistant strains were again detected. LVX + RIF confirmed its high efficacy
      against biofilm-embedded bacteria, this being the most effective therapy (-5.1
      against MSSA). The emergence of RIF-resistant strains with SXT + RIF poses
      serious concerns for its use in clinical practice. Interestingly, LZD + RIF
      appears to be an appropriate alternative for PJI caused by LVX-resistant S.
      aureus.

PMID- 29374578
TI  - Mean Aortic pressure gradient and global longitudinal strain recovery after
      transcatheter aortic valve replacement - A retrospective analysis.
AB  - BACKGROUND: Global longitudinal strain (GLS) has incremental value in assessing
      left ventricular (LV) function in severe aortic stenosis and is related to
      clinical outcome after transcatheter aortic valve replacement (TAVR). We sought
      to identify relevant echocardiographic predictors of GLS improvement and
      myocardial function recovery after TAVR. METHODS: We analyzed baseline and 12
      month follow-up echocardiograms for LV strain analysis from 123 patients who
      underwent at Emory University Hospital with the Edwards SAPIEN valve between
      7/2007 and 7/2013. RESULTS: At baseline, 61 had reduced LV ejection fraction
      (LVEF) <=50% (rEF), and 80 had preserved LVEF >50% (pEF). Higher baseline mean
      pressure gradient (MPG) and aortic peak velocity (AV Vmax) predicted myocardial
      function recovery defined as >=20% improvement in global longitudinal strain (r =
      0.29, p < .001; r = 0.26, p = .002). When analyzing subjects with discordant
      changes in GLS and LVEF at follow-up, subjects with improved GLS, although
      reduced LVEF after TAVR, experienced a greater reduction in MPG and AV Vmax (-40
      vs. -30, p = 0.015; -2.3 vs. -1.9, p = .021) after the procedure. CONCLUSIONS: In
      high-risk patients undergoing TAVR for severe aortic stenosis, GLS is impaired
      and more impaired in patients with reduced EF. Higher baseline MPG predicts
      myocardial function recovery. GLS improvement after TAVR is related to relief of
      pressure overload.

PMID- 29374579
TI  - Radial artery as a graft for coronary artery bypass surgery in the era of
      transradial catheterization.
AB  - Radial artery use as a bypass conduit is well established during the past
      decades, in terms of both patency and safety. On the other hand, transradial
      catheterization causes a series of structural and functional changes to the
      vessel itself. Impairment of nitric oxide-dependent vasodilation and notable
      decrease in radial artery diameter due to intima thickening and hyperplasia,
      especially during the first 3 months after its cannulation, constitute some of
      the most important alterations on the radial artery wall and its function after a
      transradial coronary catheterization procedure. Given the constantly increasing
      numbers of these transradial catheterization procedures, the authors of this
      article focus on the current knowledge regarding the potential use of the radial
      artery as a bypass conduit, after its catheterization, also considering several
      possible mechanisms on its subsequent structural and functional changes.

PMID- 29374580
TI  - Rapid and sensitive multiplex single-tube nested PCR for the identification of
      five human Plasmodium species.
AB  - Malaria is caused by five species of Plasmodium in humans. Microscopy is
      currently used for pathogen detection, requiring considerable training and
      technical expertise as the parasites are often difficult to differentiate
      morphologically. Rapid diagnostic tests are as reliable as microscopy and offer
      faster diagnoses but possess lower detection limits and are incapable of
      distinguishing among the parasitic species. To improve global health efforts
      towards malaria control, a rapid, sensitive, species-specific, and economically
      viable diagnostic method is needed. In this study, we designed a malaria
      diagnostic method involving a multiplex single-tube nested PCR targeting
      Plasmodium mitochondrial cytochrome c oxidase III and single-stranded tag
      hybridization chromatographic printed-array strip. The detection sensitivity was
      found to be at least 40 times higher than that of agarose gel electrophoresis
      with ethidium bromide. This system also enables the identification of both single
      and mixed-species malaria infections. The assay was validated with 152 Kenyan
      samples; using nested PCR as the standard, the assay's sensitivity and
      specificity were 88.7% and 100.0%, respectively. The turnaround time required,
      from PCR preparation to signal detection, is 90min. Our method should improve the
      diagnostic speed, treatment efficacy, and control of malaria, in addition to
      facilitating surveillance within global malaria eradication programs.

PMID- 29374581
TI  - Self-confidence and affect responses to short-term sprint interval training.
AB  - The study aimed to investigate the effects of repeated sprint (RS) training on
      somatic anxiety (SA), cognitive anxiety (CA), self-confidence (SC), rating of
      perceived exertion (RPE) and repeated sprint ability (RSA) indicators in elite
      young soccer players. Thirty elite soccer players in the first football league
      (age: 17.8+/-0.9years) volunteered to participate in this study. They were
      randomly assigned to one of two groups: a repeated sprint training group (RST-G;
      n=15) and a control group (CON-G; n=15). RST-G participated in 6weeks of
      intensive training based on RS (6*(20+20m) runs, with 20s passive recovery
      interval between sprints, 3 times/week). Before and after the 6-week
      intervention, all participants performed a RSA test and completed a Competitive
      Scale Anxiety Inventory (CSAI-2) and the RPE. After training RST-G showed a very
      significant (p<0.000) increase in RSA total time performance relative to
      controls. Despite the faster sprint pace, the RPE also decreased significantly
      (p<0.005) in RST-G, and their self confidence was significantly greater (p<0.01),
      while the cognitive (p<0.01) and somatic (p<0.000) components of their anxiety
      state decreased. When practiced regularly, short bouts of sprint exercises
      improve anaerobic performance associated with a reduction in anxiety state and an
      increase in SC which may probably boost competitive performance.

PMID- 29374583
TI  - A Right Insight in Cardiogenic Shock to Get It Right.

PMID- 29374582
TI  - Spontaneous activity forms a foundation for odor-evoked activation maps in the
      rat olfactory bulb.
AB  - Fluctuations in spontaneous activity have been observed by many neuroimaging
      techniques, but because these resting-state changes are not evoked by stimuli, it
      is difficult to determine how they relate to task-evoked activations. We
      conducted multi-modal neuroimaging scans of the rat olfactory bulb, both with and
      without odor, to examine interaction between spontaneous and evoked activities.
      Independent component analysis of spontaneous fluctuations revealed resting-state
      networks, and odor-evoked changes revealed activation maps. We constructed
      simulated activation maps using resting-state networks that were highly
      correlated to evoked activation maps. Simulated activation maps derived by
      intrinsic optical signal (IOS), which covers the dorsal portion of the glomerular
      sheet, significantly differentiated one odor's evoked activation map from the
      other two. To test the hypothesis that spontaneous activity of the entire
      glomerular sheet is relevant for representing odor-evoked activations, we used
      functional magnetic resonance imaging (fMRI) to map the entire glomerular sheet.
      In contrast to the IOS results, the fMRI-derived simulated activation maps
      significantly differentiated all three odors' evoked activation maps.
      Importantly, no evoked activation maps could be significantly differentiated
      using simulated activation maps produced using phase-randomized resting-state
      networks. Given that some highly organized resting-state networks did not
      correlate with any odors' evoked activation maps, we posit that these resting
      state networks may characterize evoked activation maps associated with odors not
      studied. These results emphasize that fluctuations in spontaneous activity form a
      foundation for active processing, signifying the relevance of resting-state
      mapping to functional neuroimaging.

PMID- 29374584
TI  - Cataract, phacoemulsification and intraocular pressure: Is the anterior segment
      anatomy the missing piece of the puzzle?
AB  - Cataract extraction is a safe and effective surgery that has a lowering effect on
      the intraocular pressure. The specific mechanisms for this effect are still
      unclear. A direct inflammatory effect on the trabecular meshwork, alteration of
      the blood aqueous barrier, changes in the ciliary body and mechanical changes of
      the anterior segment anatomy are the key to understand cataract surgery and it's
      effects on aqueous humor dynamics. Additionally, with the advent of AS OCT,
      changes in the anterior segment of the eye have been studied and several
      parameters (such as lens vault, angle opening distance and anterior chamber
      depth) have been identified as predictors of intraocular pressure change. In eyes
      with narrow angles there is a greater drop in intraocular pressure after cataract
      surgery and it is correlated with parameters related to anterior chamber space.
      It is safe to affirm that cataract surgery is an important part of the modern
      glaucoma treatment and evidence should be analyzed as part of a bigger picture in
      order to more accurately understand its clinical relevance.

PMID- 29374587
TI  - Clinical outcome of multidrug-resistant tuberculosis patients receiving
      standardized second-line treatment regimen in China.
AB  - OBJECTIVES: The aim of this study was to retrospectively analyze the clinical
      outcome and the risk factors associated with poor outcome of MDR-TB patients
      receiving standardized second-line treatment regimen in China. METHODS: Between
      January 2008 and December 2010, a total of 12,100 clinical diagnosed TB cases at
      high risk of drug-resistant TB (DR-TB) were enrolled in this study. Routine
      follow-up tests were conducted every month during the 6-month intensive phase,
      and every two months during the 18-month continuation phase. RESULTS: On the
      basis of phenotypical drug susceptibility test (DST) results, 2322 MDR-TB
      patients were confirmed, of which 1542 further received standardized second-line
      anti-TB regimen. The treatment success rate was 47.6% (734/1542): 688 patients
      (44.6%) were cured and 46 (3.0%) completed treatment. The percentage of cases
      with favorable outcome in previously untreated patients (57.6%) was significantly
      higher than that in treatment-experienced patients (46.1%, OR: 1.58, 95% CI: 1.17
      2.14). In addition, a significant lower percentage of male MDR-TB cases with
      favorable outcome (45.8%) was observed using female MDR-TB cases as a reference
      (52.0%, OR: 1.31, 95% CI: 1.03-1.60). The proportion of MDR-TB cases with
      favorable outcome was significantly decreased in older age groups. CONCLUSIONS:
      In conclusion, our data demonstrate that less than half of these patients
      receiving standardized second-line treatment regimen meet the definition of
      successful treatment during a 3-year period in China. More attention should be
      paid to the MDR-TB population at high-risk of poor clinical outcome, including
      male, elderly age, and those who have received prior treatment.

PMID- 29374585
TI  - Unrelated Donor Transplantation in Children with Thalassemia using Reduced
      Intensity Conditioning: The URTH Trial.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) can cure transfusion
      dependent thalassemia (TDT). In a multicenter trial we investigated the efficacy
      of reduced-intensity conditioning (RIC) before unrelated donor (URD) HSCT in
      children with TDT. Thirty-three children, ages 1 to 17 years, received bone
      marrow (BM) or umbilical cord blood (UCB) allografts. Median time to neutrophil
      engraftment was 13 days (range, 10 to 25) and 24 days (range, 18 to 49) and
      platelet engraftment 23 days (range, 12 to 46) and 50 days (range, 31 to 234)
      after BM and UCB allografts, respectively. With a median follow-up of 58 months
      (range, 7 to 79), overall and thalassemia-free survival was 82% (95% CI, .64% to
      .92%) and 79% (95% CI, .6% to .9%), respectively. The cumulative incidence of
      grades II to IV acute graft-versus-host disease (GVHD) after BM and UCB
      allografts was 24% and 44%; the 2-year cumulative incidence of chronic extensive
      GVHD was 29% and 21%, respectively; 71% of BM and 91% of UCB recipients
      discontinued systemic immunosuppression by 2 years. Six patients who had Pesaro
      risk class 2 (n = 5) and class 3 (n = 1) died of GVHD (n = 3), viral pneumonitis
      (n = 2) and pulmonary hemorrhage (n = 1). Outcomes after this RIC compared
      favorably with URD HSCT outcomes for TDT and supported engraftment in 32 of 33
      patients. Efforts to reduce GVHD and infectious complications are being pursued
      further.

PMID- 29374586
TI  - A tRNA's fate is decided at its 3' end: Collaborative actions of CCA-adding
      enzyme and RNases involved in tRNA processing and degradation.
AB  - tRNAs are key players in translation and are additionally involved in a wide
      range of distinct cellular processes. The vital importance of tRNAs becomes
      evident in numerous diseases that are linked to defective tRNA molecules. It is
      therefore not surprising that the structural intactness of tRNAs is continuously
      scrutinized and defective tRNAs are eliminated. In this process, erroneous tRNAs
      are tagged with single-stranded RNA sequences that are recognized by degrading
      exonucleases. Recent discoveries have revealed that the CCA-adding enzyme -
      actually responsible for the de novo synthesis of the 3'-CCA end - plays an
      indispensable role in tRNA quality control by incorporating a second CCA triplet
      that is recognized as a degradation tag. In this review, we give an update on the
      latest findings regarding tRNA quality control that turns out to represent an
      interplay of the CCA-adding enzyme and RNases involved in tRNA degradation and
      maturation. In particular, the RNase-induced turnover of the CCA end is now
      recognized as a trigger for the CCA-adding enzyme to repeatedly scrutinize the
      structural intactness of a tRNA. This article is part of a Special Issue
      entitled: SI: Regulation of tRNA synthesis and modification in physiological
      conditions and disease edited by Dr. Boguta Magdalena.

PMID- 29374588
TI  - Acute kidney injury in patients using low dose (3 mg/kg/day) of gentamicin under
      therapeutic dose monitoring.

PMID- 29374589
TI  - Functional activity of maternal and cord antibodies elicited by an
      investigational group B Streptococcus trivalent glycoconjugate vaccine in
      pregnant women.
AB  - OBJECTIVES: The main aim of this exploratory study was to evaluate functional
      activity of antibodies elicited by a maternal Group B Streptococcus (GBS)
      investigational vaccine composed of capsular polysaccharides Ia, Ib, and III
      conjugated to genetically detoxified Diphtheria toxin CRM197. The second
      objective was to investigate the relationship between serotype-specific IgG
      concentrations and functional activity in maternal and cord sera. METHODS:
      Maternal and cord sera collected at baseline and at delivery from vaccine and
      placebo recipients during a double-blind placebo-controlled Phase II study
      (www.clinicaltrials.gov, NCT01446289) were tested in an opsono-phagocytic
      bacterial killing assay. Cord sera from vaccine recipients were also passively
      transferred to newborn mice to investigate conferred protection against bacterial
      challenge. RESULTS: Antibody-mediated GBS phagocytic killing was significantly
      increased in maternal serum at delivery and in cord sera from the investigational
      vaccine group as compared to the placebo group. Anti-capsular IgG concentrations
      above 1 ug/mL mediated in vitro killing against GBS strains belonging to all
      three serotypes and IgG levels correlated with functional titers. Passively
      administered cord sera elicited a dose-dependent protective response against all
      GBS serotypes in the in vivo model. CONCLUSIONS: The maternal vaccine elicited
      functional antibodies that were placentally transferred. Anti-capsular IgG
      concentrations in maternal and cord sera were predictive of functional activity
      and in vivo protection in the mouse model.

PMID- 29374590
TI  - Influence of Bacillus subtilis ANSB060 on growth, digestive enzyme and aflatoxin
      residue in Yellow River carp fed diets contaminated with aflatoxin B1.
AB  - Aflatoxin B1 (AFB1) elicits serious threats to public health due to its
      widespread occurrence, as well as its teratogenic, carcinogenic and mutagenic
      effects. This study aimed to evaluate the toxicity of AFB1 and assess the
      ameliorative efficacy of Bacillus subtilis ANSB060 on aflatoxicosis in Yellow
      River carp. A total of 750 juvenile Yellow River carp were allocated into five
      dietary treatments for 60 days. Diet C0 represented for the negative control,
      diet M0 containing about 50 MUg AFB1/kg diet represented for the positive
      control, and diet M0.25, M0.5 and M1.0 was diet M0 supplemented with B. subtilis
      ANSB060 at a dose of 0.25 * 109, 0.5 * 109 and 1.0 * 109 CFU/kg diet,
      respectively. The results showed that supplementation of strain ANSB060 restored
      the reduced body weight and enhanced feed conversion ratio of carp induced by
      AFB1 towards normal. ANSB060 could also relieve the alterations in hepatic
      morphology, improve digestive enzyme activities of hepatopancreas and intestine,
      as well as decrease AFB1 residues in carp's hepatopancreas and gonad. It is
      concluded that ANSB060 has a protective effect in carp with aflatoxicosis, with a
      promising potential in feed industrial applications.

PMID- 29374591
TI  - In vitro genotoxicity assessment of dinitroaniline herbicides pendimethalin and
      trifluralin.
AB  - Pendimethalin and trifluralin are widely used dinitroaniline herbicides. Both
      compounds can be found as residue levels in agricultural products. This study was
      conducted in order to provide necessary information for the risk assessment of
      pendimethalin and trifluralin. In this study, reactive oxygen species (ROS)
      levels were measured to examine the potential of both compounds to induce
      oxidative damage in Chinese hamster lung fibroblast (V79) cells. Also, the
      genotoxic effects of pendimethalin and trifluralin at the concentration range of
      1-500 MUM was determined. Single cell gel electrophoresis (comet) and
      micronucleus assays were used on human peripheral lymphocytes and V79 cells for
      the genotoxicity assessment. The cell viability of two dinitroaniline herbicides
      were determined by the use of neutral red uptake assay on V79 cells. IC50 values
      were determined as 66 MUM and 128 MUM for pendimethalin and trifluralin,
      respectively. They significantly increased ROS levels on V79 cells for 1-24 h.
      Both herbicides significantly induced the DNA damage and showed genotoxicity on
      lymphocytes and V79 cells. Micronucleus frequency increased significantly after
      pendimethalin and trifluralin treatment of the lymphocytes and V79 cells.
      Therefore, we concluded that both of the herbicides induced the genotoxicity
      through the activation of oxidative stress pathway and chromosomal damage.

PMID- 29374592
TI  - Risk assessment of aflatoxin B1 exposure from maize and peanut consumption in
      Indonesia using the margin of exposure and liver cancer risk estimation
      approaches.
AB  - Aflatoxin B1 (AfB1) is a secondary fungal metabolite product widely found in many
      foodstuffs and considered a public health concern worldwide due to its
      genotoxicity and carcinogenicity. Tropical climate and inappropriate food safety
      practices in Indonesia are the favorable conditions for AfB1 contamination of
      foodstuffs. Despite these challenges, there has been a limited number of risk
      assessment of AfB1 conducted in Indonesia. Therefore, this paper aimed to gather
      all available occurrence data of AfB1 in maize and peanut originating from
      Indonesia and used the occurrence data to evaluate the risk of exposure to AfB1
      using the Margin of Exposure (MOE) and the quantitative liver cancer risk
      approaches established by EFSA and FAO/WHO respectively. Risk assessment using
      both the MOE and quantitative liver cancer risk approaches revealed that AfB1
      exposure from maize and peanut consumption in Indonesia is of concern. The MOE
      values derived from consumption of maize and peanut originating from Indonesia
      were generally below 10,000, and for several occurrence data were even below
      1000. The estimated number of liver cancer cases associated with AfB1 exposure
      generally was above the 0.1 cancer cases/100,000 individuals/75 years. Altogether
      the evaluation reveals the urgency for risk management of AfB1 in Indonesia.

PMID- 29374593
TI  - Relationship between LINE-1 methylation pattern and pesticide exposure in urban
      sprayers.
AB  - Recently a relationship has been reported between pesticide exposure and changes
      in global DNA methylation patterns. Urban sprayers are a particularly vulnerable
      population because of the high risk of pesticide exposure that their work
      implies. Therefore, the aim of this study was to estimate the changes in the Long
      Interspersed Nucleotide Element (LINE-1) in urban sprayers and its relationship
      with pesticide exposure. The study population consisted of 190 individuals
      stratified into three study groups: no occupational pesticide exposure; moderate
      exposure, and high exposure. Pesticide exposure and other external factors such
      as diet, lifestyle, and others were evaluated through a validated questionnaire,
      and the butyrylcholinesterase enzyme activity was evaluated
      spectrophotometrically and used as exposure biomarker. DNA methylation was
      evaluated by pyrosequencing on bisulfite-treated DNA. The results showed a
      significant decrease of %5mC in both the moderate- and high-exposure groups with
      respect to the non-exposed group (p < 0.05). In addition, alcohol intake was
      associated with a higher percentage of LINE- 1 methylation. In conclusion, our
      results suggest that occupational pesticide exposure and external factors appears
      to modify the DNA methylation pattern measured through LINE-1.

PMID- 29374594
TI  - High resolution UPLC-MS/MS profiling of polyphenolics in the methanol extract of
      Syzygium samarangense leaves and its hepatoprotective activity in rats with CCl4
      induced hepatic damage.
AB  - Oxidative stress plays a crucial role in the development of several liver
      diseases. Many natural polyphenols can attenuate oxidative stress and liver
      injury. In this study, a phytochemical profiling of a methanol extract from
      leaves of Syzygium samarangense revealed 92 compounds belonging to flavonoids,
      phenolic acids, condensed tannins, and ellagitannins. The S. samarangense extract
      exhibited a noticeable antioxidant activity with an EC50 of 5.80 MUg/mL measured
      by DPPH scavenging capacity assay, 2632 Trolox equivalents, 10 mM Fe2+
      equivalents/mg of samples by TEAC and FRAP assays, respectively. The total
      phenolic content was 419 mg gallic acid equivalent GAE/g extract. In a cell-based
      model (HaCaT cells), the extract completely inhibited ROS production induced by
      UVA, and prevented GSH-depletion and p38 phosphorylation. In addition, the
      extract exhibited a substantial antioxidant and hepatoprotective activities in
      CCl4-treated rats, with an increase in GSH (reduced glutathione) and SOD
      (superoxide dismutase) activities by 84.75 and 26.27%, respectively, and a
      decrease of 19.08, 63.05, 52.21, 37.00, 13.26, and 15.15% in MDA, ALT, AST, TB
      (total bilirubin), TC (total cholesterol), and TG (total glycerides),
      respectively. These results were confirmed by histopathological analyses. We
      believe that Syzygium samarangense is a good candidate for further evaluation as
      an antioxidant and liver protecting drug.

PMID- 29374595
TI  - Multigene delivery in mammalian cells: Recent advances and applications.
AB  - Systems for multigene delivery in mammalian cells, particularly in the context of
      genome engineering, have gained a lot of attention in biomolecular research and
      medicine. Initially these methods were based on RNA polymerase II promoters and
      were used for the production of protein complexes and for applications in cell
      biology such as reprogramming of somatic cells to stem cells. Emerging
      technologies such as CRISPR/Cas9-based genome engineering, which enable any
      alteration at the genomic level of an organism, require additional elements
      including U6-driven expression cassettes for RNA expression and homology
      constructs for designed genome modifications. For these applications, systems
      with high DNA capacity, flexibility and transfer rates are needed. In this
      article, we briefly give an update on some of recent strategies that facilitate
      multigene assembly and delivery into mammalian cells. Also, we review
      applications in various fields of biology that rely on multigene delivery
      systems.

PMID- 29374596
TI  - Biomolecule-embedded metal-organic frameworks as an innovative sensing platform.
AB  - Technological advancements combined with materials research have led to the
      generation of enormous types of novel substrates and materials for use in various
      biological/medical, energy, and environmental applications. Lately, the embedding
      of biomolecules in novel and/or advanced materials (e.g., metal-organic
      frameworks (MOFs), nanoparticles, hydrogels, graphene, and their hybrid
      composites) has become a vital research area in the construction of an innovative
      platform for various applications including sensors (or biosensors), biofuel
      cells, and bioelectronic devices. Due to the intriguing properties of MOFs (e.g.,
      framework architecture, topology, and optical properties), they have contributed
      considerably to recent progresses in enzymatic catalysis, antibody-antigen
      interactions, or many other related approaches. Here, we aim to describe the
      different strategies for the design and synthesis of diverse biomolecule-embedded
      MOFs for various sensing (e.g., optical, electrochemical, biological, and
      miscellaneous) techniques. Additionally, the benefits and future prospective of
      MOFs-based biomolecular immobilization as an innovative sensing platform are
      discussed along with the evaluation on their performance to seek for further
      development in this emerging research area.

PMID- 29374597
TI  - Ghrelin gene polymorphism as a genetic biomarker for prediction of therapy
      induced clearance in Egyptian chronic HCV patients.
AB  - : Ghrelin (GHRL) has important implications for liver disease. It has anti
      inflammatory effects, regulates cell proliferation, modulates the fibrogenic
      response and protects liver tissue. Genetic variations in the GHRL gene may play
      a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC)
      and hepatocellular carcinoma (HCC). Therefore, we examined the association of
      GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic
      responses to combined sofosbuvir and Simeprevir therapy for a course of 12
      successive weeks in Egyptian chronic hepatitis C (CHC) patients. METHODS: Human
      genomic and clinical data were collected from 100 Egyptian participants in this
      study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV
      healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with
      the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were
      determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: GHRL
      polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies
      did not differ between HCV patients and normal healthy subjects or between
      patient groups when compared according to the therapeutic response. In addition,
      we found significant lower serum GHRL levels in CHC patients compared with the
      healthy controls. However, there was no significant association of the GHRL
      rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude
      that GHRL SNPs (rs26312 and rs27647) do not affect response to combined
      sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients.

PMID- 29374598
TI  - Transcriptome analysis of starch and sucrose metabolism across bulb development
      in Sagittaria sagittifolia.
AB  - Sagittaria sagittifolia L is an important bulb vegetable that has high
      nutritional and medical value. Bulb formation and development are crucial to
      Sagittaria sagittifolia; however, its sucrose metabolism is poorly understood and
      there are a lack of sufficient transcriptomic and genomic data available to fully
      understand the molecular mechanisms underlying bulb formation and development as
      well as the bulb transcriptome. Five cDNA libraries were constructed at different
      developmental stages and sequenced using high-throughput Illumina RNA sequencing.
      From approximately 63.53 Gb clean reads, a total of 60,884 unigenes, with an
      average length of 897.34 bp and N50 of 1.368 kb, were obtained. A total of 36,590
      unigenes were successfully annotated using five public databases. Across
      different developmental stages, 4195, 827, 832, 851, and 1494 were differentially
      expressed in T02, T03, T04, T05, and T06 libraries, respectively. Gene ontology
      (GO) analysis revealed several differentially-expressed genes (DEGs) associated
      with catalytic activity, binding, and transporter activity. The Kyoto
      encyclopedia of genes and genomes (KEGG) revealed that these DEGs are involved in
      physiological and biochemical processes. RT-qPCR was used to profile the
      expression of these unigenes and revealed that the expression patterns of the
      DEGs were consistent with the transcriptome data. In this study, we conducted a
      comparative gene expression analysis at the transcriptional level using RNA-seq
      across the different developmental stages of Sagittaria sagittifolia. We
      identified a set of genes that might contribute to starch and sucrose metabolism,
      and the genetic mechanisms related to bulblet development were also explored.
      This study provides important data for future studies of the genetic and
      molecular mechanisms underlying bulb formation and development in Sagittaria
      sagittifolia.

PMID- 29374599
TI  - pH-triggered charge-reversible of glycol chitosan conjugated carboxyl graphene
      for enhancing photothermal ablation of focal infection.
AB  - : Subcutaneous abscesses infected by multidrug-resistant bacteria are becoming an
      increasing challenge to human health. To address this challenge, a surface
      adaptive and biocompatible glycol chitosan conjugated carboxyl graphene (GCS-CG)
      is developed, which exhibits unique self-adaptive target to the acidic
      microenvironment of abscess (~pH 6.3) and no damage to the healthy tissue (pH
      7.4) around the abscess. Originally, following conjugated with GCS, the
      absorbance of CG obviously increases in the near-infrared (NIR) region, enabling
      GCS-CG to generate an increment amount of heat. GCS-CG shows fast pH-responsive
      surface charge transition from negative to positive, which presents strong
      adherence to negatively charged bacteria surface in abscess, while exhibits poor
      affinity to host cells in healthy tissues. The local temperature of NIR
      irradiated GCS-CG is estimated to be higher than their ambient temperature,
      ensuring targeted heating and eradicating the bacteria to reduce the damage to
      tissue; hence, wound healing is accelerated. Moreover, the in vitro and in vivo
      biosafety results demonstrate that GCS-CG presents greatly biocompatible even at
      a high concentration of 1 mg.mL-1. Given the above advantages as well as the
      simple preparation, graphene developed here may provide a new potential
      application as a useful antibacterial agent in the areas of healthcare. STATEMENT
      OF SIGNIFICANCE: A surface-adaptive nanomaterial, glycol chitosan conjugated
      carboxyl graphene (GCS-CG) is developed, which realizes the acidity-triggered
      bacteria targeting. GCS-CG can result in direct thermal ablation of bacteria and
      enhancement of the infected wound healing, but exhibit no damage to healthy
      tissues. The pH-responsive GCS-CG described here, containing no antibiotics, has
      great potentials in treating bacterial infection and even multidrug-resistant
      bacteria.

PMID- 29374600
TI  - Corneal regeneration: A review of stromal replacements.
AB  - : Corneal blindness is traditionally treated by transplantation of a donor
      cornea, or in severe cases by implantation of an artificial cornea or
      keratoprosthesis. Due to severe donor shortages and the risks of complications
      that come with artificial corneas, tissue engineering in ophthalmology has become
      more focused on regenerative strategies using biocompatible materials either with
      or without cells. The stroma makes up the bulk of the corneal thickness and
      mainly consists of a tightly interwoven network of collagen type I, making it
      notoriously difficult to recreate in a laboratory setting. Despite the challenges
      that come with corneal stromal tissue engineering, there has recently been
      enormous progress in this field. A large number of research groups are working
      towards developing the ideal biomimetic, cytocompatible and transplantable
      stromal replacement. Here we provide an overview of the approaches directed
      towards tissue engineering the corneal stroma, from classical collagen gels,
      films and sponges to less traditional components such as silk, fish scales,
      gelatin and polymers. The perfect stromal replacement has yet to be identified
      and future research should be directed at combined approaches, in order to not
      only host native stromal cells but also restore functionality. STATEMENT OF
      SIGNIFICANCE: In the field of tissue engineering and regenerative medicine in
      ophthalmology the focus has shifted towards a common goal: to restore the corneal
      stroma and thereby provide a new treatment option for patients who are currently
      blind due to corneal opacification. Currently the waiting lists for corneal
      transplantation include more than 10 million patients, due to severe donor
      shortages. Alternatives to the transplantation of a donor cornea include the use
      of artificial cornea, but these are by no means biomimetic and therefore do not
      provide good outcomes. In recent years a lot of work has gone into the
      development of tissue engineered scaffolds and other biomaterials suitable to
      replace the native stromal tissue. Looking at all the different approaches
      separately is a daunting task and up until now there was no review article in
      which every approach is discussed. This review does include all approaches, from
      classical tissue engineering with collagen to the use of various alternative
      biomaterials and even fish scales. Therefore, this review can serve as a
      reference work for those starting in the field and but also to stimulate
      collaborative efforts in the future.

PMID- 29374601
TI  - AKT2 contributes to increase ovarian cancer cell migration and invasion through
      the AKT2-PKM2-STAT3/NF-kappaB axis.
AB  - Multiple studies have shown that protein kinase Bbeta (AKT2) is involved in the
      development and progression of ovarian cancer, however, its precise role remains
      unclear. Here we explored the underlying molecular mechanisms how AKT2 promotes
      ovarian cancer progression. We examined the effects of AKT2 in vitro in two
      ovarian cancer cell lines (SKOV3 and HEY), and in vivo by metastasis assay in
      nude mice. The migration and invasion ability of SKOV3 and HEY cells was
      determined by transwell assay. Overexpression and knockdown (with shRNA)
      experiments were carried out to unravel the underlying signaling mechanisms
      induced by AKT2. Overexpression of AKT2 led to increased expression of pyruvate
      kinase (PKM2) in ovarian cancer cells and in lung metastatic foci from nude mice.
      Elevated AKT2/PKM2 expression induced cell migration and invasion in vitro, as
      well as lung metastasis in vivo; silencing AKT2 blocked these effects. Meanwhile,
      PKM2 overexpression was unable to increase AKT2 expression. The expressions of p
      PI3K, p-AKT2, and PKM2 were increased when stimulated by epidermal growth factor
      (EGF); however, these expressions were blocked when inhibited the PI3K by
      LY294002. STAT3 expression was elevated and NF-kappaB p65 nuclear translocation
      was activated both in vitro and in vivo when either AKT2 or PKM2 was
      overexpressed; and these effects were inhibited when silencing AKT2 expression.
      Taken together, AKT2 increases the migration and invasion of ovarian cancer cells
      in vitro and promotes lung metastasis in nude mice in vivo through PKM2-mediated
      elevation of STAT3 expression and NF-kappaB activation. In conclusion, we
      highlight a novel mechanism of the AKT2-PKM2-STAT3/NF-kappaB axis in the
      regulation of ovarian cancer progression, and our work suggested that both AKT2
      and PKM2 may be potential targets for the treatment of ovarian cancer.

PMID- 29374602
TI  - Reduction in endogenous cardiac steroids protects the brain from oxidative stress
      in a mouse model of mania induced by amphetamine.
AB  - OBJECTIVES: Bipolar disorder (BD) is a severe mental illness characterized by
      episodes of mania and depression. Numerous studies have implicated the
      involvement of endogenous cardiac steroids (CS), and their receptor, Na+, K+ 
      ATPase, in BD. The aim of the present study was to examine the role of brain
      oxidative stress in the CS-induced behavioral effects in mice. METHODS:
      Amphetamine (AMPH)-induced hyperactivity, assessed in the open-field test, served
      as a model for manic-like behavior in mice. A reduction in brain CS was obtained
      by specific and sensitive anti-ouabain antibodies. The level of oxidative stress
      was tested in the hippocampus and frontal cortex by measuring the activity of
      antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPx), as well as the levels of antioxidant non-protein thiols (NPSH)
      and oxidative damage biomarkers thiobarbituric acid reactive substances (TBARS)
      and protein carbonyl (PC). RESULTS: AMPH administration resulted in a marked
      hyperactivity and increased oxidative stress, as manifested by increased SOD
      activity, decreased activities of CAT and GPx, reduced levels of NPSH and
      increased levels of TBARS and PC. The administration of anti-ouabain antibodies,
      which reduced the AMPH-induced hyperactivity, protected against the concomitant
      oxidative stress in the brain. CONCLUSIONS: Our results demonstrate that
      oxidative stress participates in the effects of endogenous CS on manic-like
      behavior induced by AMPH. These finding support the notion that CS and oxidative
      stress may be associated with the pathophysiology of mania and BD.

PMID- 29374603
TI  - Novel insights into mitochondrial molecular targets of iron-induced
      neurodegeneration: Reversal by cannabidiol.
AB  - Evidence has demonstrated iron accumulation in specific brain regions of patients
      suffering from neurodegenerative disorders, and this metal has been recognized as
      a contributing factor for neurodegeneration. Using an experimental model of brain
      iron accumulation, we have shown that iron induces severe memory deficits that
      are accompanied by oxidative stress, increased apoptotic markers, and decreased
      synaptophysin in the hippocampus of rats. The present study aims to characterize
      iron loading effects as well as to determine the molecular targets of cannabidiol
      (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria.
      Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron
      induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of
      mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity. CBD
      rescued mitochondrial ferritin and epigenetic modulation of mtDNA, and restored
      succinate dehydrogenase activity in iron-treated rats. These findings provide new
      insights into molecular targets of iron neurotoxicity and give support for the
      use of CBD as a disease modifying agent in the treatment of neurodegenerative
      diseases.

PMID- 29374604
TI  - Confocal calcium imaging analysis of respiratory-related burst activity in the
      parafacial region.
AB  - The parafacial respiratory group (pFRG) surrounding the ventrolateral part of the
      facial motor nucleus is one of respiratory rhythm generators that consists of pre
      inspiratory (Pre-I) neurons. Previous studies showed that most of the Pre-I
      neurons locating in the Phox2b cluster of the rostral ventral medulla were also
      Phox2b positive and intrinsically CO2 sensitive. However, it is not clear what
      percentage of Phox2b-expressing cells in the pFRG of the ventral medulla are Pre
      I neurons. To address this issue, we analyzed the activity of Phox2b-positive
      cells by calcium imaging using a confocal laser microscope in transgenic rats in
      which Phox2b-positive cells expressed EYFP. We found that more than 60% of the
      EYFP/Phox2b-positive cells showed Pre-I neuron-like rhythmic burst activity in
      the parafacial region of newborn rat.

PMID- 29374605
TI  - An Experimental Study on Repeated Brief Ischemia in Promoting Sciatic Nerve
      Repair and Regeneration in Rats.
AB  - BACKGROUND: Research has shown that ischemic preconditioning reduced the severity
      of ischemia-reperfusion injury in brain in rats, we have a hypothesis that
      repeated brief ischemia has positive effects on peripheral nerve damage. This
      study was conducted to investigate the potential protective effects of repeated
      brief ischemia on peripheral nerve regeneration using a rat model of experimental
      sciatic nerve transection injury. METHODS: Treatment groups (groups A-D) received
      repeated, brief ischemia every 1 day/2 days/3 days/7 days. After surgery for 4,
      8, 12 weeks, we evaluated sciatic functional index test, gastrocnemius muscle wet
      mass, axon and nerve fiber diameter, density, G-ratio, immunohistochemistry of S
      100, vascular endothelial growth factor (VEGF), and the ultrastructure of the
      nerves. RESULTS: Sciatic functional index test and muscle wet mass were improved
      on the repeated brief ischemia groups. Ischemia treatment resulted in a
      significant increase in axon and nerve fiber density as well as S-100 and VEGF
      positive cell, which indicated that repeated brief ischemia promotes Schwann cell
      proliferation and reconstruction. CONCLUSIONS: This study exhibits the positive
      effects of repeated brief ischemia in sciatic nerve transection injury, possibly
      in part because it can improve VEGF and the physiologic state of Schwann cells in
      the ischemic environment and then accelerate the ability of neurite outgrow.

PMID- 29374606
TI  - Factors Affecting Long-Term Postoperative Narcotic Use in Discectomy Patients.
AB  - BACKGROUND: Long-term narcotic use has risks and potentially life-threatening
      opioid-related side effects. Extended narcotic use in patients undergoing
      discectomy raises concerns of other underlying causes of pain or overprescription
      and/or abuse. The goal of this study was to determine which factors have an
      effect on active narcotic prescription >3 months after discectomy. METHODS: The
      PearlDiver Database was used in this study. Patients 30-55 years old undergoing
      discectomy without fusions were queried for active narcotic drug prescription
      occurring >30 days and >3 months after original surgery. Medical co-diagnoses
      were independently analyzed for effects on long-term active narcotic
      prescriptions. Prior narcotic use was defined by use within 4 months before
      surgery. RESULTS: Of 1321 patients undergoing discectomy, 621 had actively
      prescribed narcotics >3 months after surgery. Preoperative narcotic use had the
      largest effect on odds of postoperative prescription (odds ratio [OR] = 3.4).
      Medical comorbidities increasing odds of long-term narcotic prescriptions
      included migraines (OR = 1.4), diabetes mellitus (OR = 1.4), depression (OR =
      1.6), and smoking (OR = 1.9). CONCLUSIONS: Narcotic abuse is a serious problem
      rooted in overprescription of these drugs, which has ultimately led to much more
      caution in prescribing among physicians. Because pain management and drug
      prescription must be balanced, identifying patients who may be susceptible to
      narcotic overprescription is important. Patients with co-diagnoses increasing
      odds of long-term narcotic prescriptions would benefit from early and continual
      postsurgical follow-up to ensure accurate pain management and to determine if
      narcotic prescriptions are justly warranted in the later postoperative period.

PMID- 29374607
TI  - Incidence, Comorbidities, and Mortality in Idiopathic Normal Pressure
      Hydrocephalus.
AB  - OBJECT: To investigate the incidence, comorbidities, mortality, and causes of
      death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of
      536 patients with possible NPH from a defined population with a median follow-up
      time of 5.1 years, (range 0.04-19.9 years) was included in the study. Patients
      were evaluated by brain imaging and intraventricular pressure monitoring, with a
      brain biopsy specimen immunostained against amyloid-beta and hyperphosphorylated
      tau. Hospital records were reviewed for vascular diseases and type 2 diabetes
      mellitus (T2DM). Death certificates and yearly population of the catchment area
      were obtained from national registries. RESULTS: A total of 283 patients had a
      clinical diagnosis of iNPH, leading to a median annual incidence of 1.58 iNPH
      patients per 100,000 inhabitants (range, 0.8-4.5). Alzeimer disease-related brain
      biopsy findings were less frequent in iNPH patients than in non-iNPH patients (P
      < 0.05). An overrepresentation of hypertension (52% vs. 33%, P < 0.001) and T2DM
      (23% vs. 13%, P = 0.002) was noted in iNPH patients. Age (hazard ratio [HR]
      1.04/year, 95% confidence interval [CI] 1.03-1.06, P < 0.001) and T2DM (HR 1.63,
      95% CI 1.23-2.16, P < 0.001) increased the risk of death in the iNPH patients and
      in the total population. iNPH was associated with decreased risk of death (HR
      0.63, 95% CI 0.50-0.78, P < 0.001). The most frequent causes of death were
      cardiovascular and cerebrovascular disease. Dementia as a cause of death was more
      common in non-iNPH patients (27% vs. 10%, P < 0.001). CONCLUSIONS: Hypertension
      and T2DM are common in iNPH and the latter causes excess mortality in the
      affected patients.

PMID- 29374608
TI  - Single-Center Clinical Characteristics and Treatment Experience of Foramen Magnum
      Neurenteric Cyst: Report of 6 Cases and Brief Review of the Literature.
AB  - OBJECTIVE: To retrospectively analyze the clinical data of 6 patients with
      foramen magnum (FM) neurenteric (NE) cysts, and summarize the clinical
      characteristics and treatment experience for this rare disease in our single
      center. METHODS: Between January 2011 and December 2015, 6 patients with FM NE
      cyst were surgically treated at Xuan Wu Hospital of Capital Medical University.
      We summarize the treatment experience of these patients through a retrospective
      review of the clinical information, imaging features, surgical details, and
      follow-up outcomes. RESULTS: All 6 patients were female, ranging in age from 15
      to 54 years (mean age, 36.8 +/- 12.9 years). Occipital headache along with
      cranial nerve injury were the most common symptoms. Preoperative brain magnetic
      resonance imaging identified all lesions in the FM region, with an oblong or
      lobulated shape. The surgical approach was far lateral in 4 patients and
      suboccipital midline in 2 patients. Total lesion removal was completed in 4
      patients, and subtotal excision was performed in the other 2 patients, in whom
      the cyst wall was intensely adherent to surrounding structures. In all 6
      patients, the preoperative symptoms were significantly relieved after surgery. No
      recurrence was seen after a mean follow-up of 27.3 months (range, 3-70 months).
      CONCLUSIONS: Our present study identified a female predominance among patients
      with intracranial FM NE cyst. Surgical excision is the optimum treatment strategy
      for this rare disease. Our findings indicate that subtotal removal of an FM NE
      cyst may be associated with favorable outcomes, but strict long-term follow up is
      needed.

PMID- 29374609
TI  - Dural Repair in Cranial Surgery Is Associated with Moderate Rates of
      Complications with Both Autologous and Nonautologous Dural Substitutes.
AB  - OBJECTIVE: Duraplasty, a common neurosurgical intervention, involves synthetic or
      biological graft placement to ensure dural closure. The objective of this study
      is to advance our understanding of the use of dural substitutes in cranial
      surgery. METHODS: The PubMed database was systematically searched to identify
      studies published over the past decade (2007-2017) that described duraplasty
      procedures. Clinical data were disaggregated and analyzed for the comparisons of
      biological versus synthetic grafts. RESULTS: A total of 462 cases were included
      in the quantitative synthesis. Overall, the most common indication for duraplasty
      was tumor resection (53%). Allografts were more frequently used in decompression
      for Chiari malformations compared with xenografts and synthetic grafts (P <
      0.001). Xenografts were more frequently used in decompressive hemicraniectomy
      procedures for evacuation of acute subdural hematomas over allografts and
      synthetics (P < 0.001). Synthetic grafts were more frequently used in tumor cases
      than biological grafts (P = 0.002). The cumulative complication rate for dural
      substitutes of all types was 11%. There were no significant differences in
      complication rates among the 3 types of dural substitutes. CONCLUSIONS: Dural
      substitutes are commonly used to ensure dural closure in a variety of cranial
      procedures. This study provides greater insight into duraplasty practices and
      highlights the moderate complication rate associated with the procedure. Future
      studies are needed to determine the safety and efficacy of such procedures in
      larger prospective cohorts.

PMID- 29374610
TI  - Anatomical Study of the Posterior Ascending Artery: Application to C2 Pedicle
      Screw Placement.
AB  - OBJECTIVE: Anatomy of the posterior ascending artery (PAA) has been well
      documented. The PAA forms an apical arcade, which supplies the small branches to
      the tip of the dens. However, morphometrics of this artery such as diameter and
      distance from the midline, which could be applied to the diagnosis and surgical
      procedure, are scant. We aimed to investigate the anatomy of the PAA in order to
      apply our findings to surgical procedures such as C2 pedicle screw placement.
      METHODS: Ten sides from 5 Caucasian cadaveric heads in which red latex was
      injected were used. The origin of the PAA, diameter of the PAA and apical arcade,
      and the distance from midline were recorded. RESULTS: Diameters of the PAA and
      apical arcade were approximately 1 mm and 0.7 mm, respectively. Distance from the
      midline to the PAA was approximately 7 mm. In 1 specimen, the os odontoideum was
      observed on top of the dens. CONCLUSIONS: The result of this study could provide
      anatomic knowledge, which is important for C2 pedicle screw placement to the
      spine surgeon.

PMID- 29374611
TI  - Frugal Malleable Microdissectors and Arachnoid Knives for Microneurosurgery.
AB  - BACKGROUND: Similar to most of the other medical and surgical fields,
      neurosurgery has changed drastically in recent decades, especially in
      instrumentation and equipment. Safety, scope of treating initially considered
      nontreatable neurosurgical conditions, and prognosis of most neurosurgical
      procedures have improved significantly. Newer instruments and equipments are
      being introduced exponentially, leading to tremendous cost escalation of
      neurosurgical treatment. However, equitable distribution of neurosurgical
      services in society is far from reality. We need to look back and learn from our
      teachers and forefathers of neurosurgery their innovative ways to accomplish
      difficult procedures without advanced tools and techniques. Microneurosurgery is
      considered a highly skilled technique, and instruments used for it are delicate,
      precise, and costlier than similar instruments for macroneurosurgery. TECHNIQUE
      AND CONCLUSION: Frugal innovative techniques and tools are presented for making
      stainless steel wire and plate microdissectors that are effective for
      microneurosurgical procedures and can be helpful for neurosurgeons working in
      resource-poor settings.

PMID- 29374612
TI  - A Large Multicenter Retrospective Research on Embedded Cranioplasty and Covered
      Cranioplasty.
AB  - OBJECTIVE: Cranioplasty (CP) can be either embedded or covered, according to the
      implants used. However, determining which one is better in treating cranial
      defects is difficult. This study aimed to compare the clinical outcomes and
      complications of embedded CP and covered CP. METHODS: A multicenter retrospective
      study was undertaken with patients who underwent CP with polyetheretherketone
      (PEEK) implants and titanium implants between January 2014 and March 2017. The
      medical records of these patients were reviewed retrospectively and analyzed
      statistically. RESULTS: There were 185 patients, including 75 patients (40.5%)
      who underwent embedded CP with PEEK implants (PEEK group) and 110 patients
      (59.5%) who underwent covered CP using titanium mesh (titanium group), in this
      study. Compared with the titanium group, the incidence of overall complications
      (P = 0.03), postoperative new seizures (P = 0.01), postoperative implant exposure
      (P = 0.03), and reoperation (P = 0.01) was significantly lower in PEEK group. The
      rate of brain function improvement (P = 0.01) after CP and satisfaction with CP
      (P = 0.01) in patients in the PEEK group were higher than that in the titanium
      group. CONCLUSIONS: Our results show that embedded CP with PEEK has a distinct
      advantage in brain function improvement and fewer postoperative complications
      compared with covered CP with titanium mesh. However, the high cost of PEEK is an
      obvious drawback. This study can help both neurosurgeons and patients in choosing
      a better therapeutic method to achieve the most satisfactory outcome in treating
      cranial defects.

PMID- 29374613
TI  - Default Mode Network Changes in Moyamoya Disease Before and After Bypass Surgery:
      Preliminary Report.
AB  - OBJECTIVE: Neurocognitive impairment is often reported in moyamoya disease. We
      aimed to detect default mode network (DMN) alterations using resting-state
      functional magnetic resonance imaging and their association with neurocognitive
      impairments. In addition, the influence of surgical treatment was individually
      evaluated. METHODS: Seven patients with moyamoya disease underwent preoperative
      resting-state functional magnetic resonance imaging and neuropsychologic tests.
      We compared the resting-state networks (RSNs) of our patients with those obtained
      from relatively large cohort datasets (127 healthy controls) using group
      independent component analysis with dual regression analysis. We also explored
      correlations between RSN alterations and neuropsychologic scores. We evaluated
      individuals again 6 months after surgery to identify changes. RESULTS: Patients
      had statistically significant differences in DMN connectivity compared with
      healthy controls. There were marked changes in functional connectivity of the
      ventral DMN of patients with low working memory and performance speed scores.
      These changes were characterized by increases and decreases in various locations.
      In contrast, patients with average or high neuropsychologic scores showed similar
      connectivity to the controls. In 5 patients who underwent vascular reconstruction
      surgery, DMN functional connectivity changed to resemble that of healthy
      controls. CONCLUSIONS: In moyamoya disease, working memory and performance speed
      scores were inversely correlated to the degree of disruption of the DMN,
      suggesting a possible relationship between higher cognitive function and
      orderliness of fundamental brain networks. Vascular reconstruction surgery may
      contribute to normalization of brain networks. Analysis of RSNs may produce
      potential biomarkers for cognition in moyamoya disease.

PMID- 29374614
TI  - Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of
      Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis.
AB  - BACKGROUND & AIMS: Tests to quantify fecal levels of chymotrypsin like elastase
      family member 3 (CELA3 or elastase-1) in feces are widely used to identify
      patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic
      accuracy of this test, an ELISA, is not clear. We performed a systematic review
      and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in
      detection of EPI. METHODS: We searched PubMed, Embase, and reference lists for
      articles through November 2016 describing studies that compared fecal level of
      elastase-1 with results from a reference standard, direct method (secretin
      stimulation test), or indirect method (measurement of fecal fat) for detection of
      EPI. Sensitivity and specificity values were pooled statistically using bivariate
      diagnostic meta-analysis. RESULTS: We included total of 428 cases of EPI and 673
      individuals without EPI (controls), from 14 studies, in the meta-analysis. The
      assay for elastase-1, compared to secretin stimulation test, identified patients
      with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI,
      0.58-0.89) and specificity value of 0.88 (95% CI, 0.78-0.93). In an analysis of
      345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay
      identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI,
      0.79-0.99) and specificity value of 0.88 (95% CI, 0.59-0.97), compared to
      quantitative fecal fat estimation. In patients with low pre-test probability of
      EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and
      a false-positive rate of 11%, indicating a high yield in ruling out EPI but not
      in detection of EPI. In contrast, in patients with high pre-test probability of
      EPI (40%), approximately 10% of patients with EPI would be missed (false
      negatives). CONCLUSIONS: In a systematic review and meta-analysis of studies that
      compared fecal level of elastase-1 for detection of EPI, we found that normal
      level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low
      probability of this disorder (such as those with irritable bowel syndrome with
      diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200
      mcg/g) has a high false-positive rate.

PMID- 29374615
TI  - Prolonged Time to Diagnosis of Eosinophilic Esophagitis Despite Increasing
      Knowledge of the Disease.
AB  - Eosinophilic esophagitis (EoE) is a chronic condition characterized by
      eosinophilic-predominant inflammation and esophageal dysfunction.1,2 EoE
      represents a rapidly increasing cause of morbidity and a growing health problem.

PMID- 29374616
TI  - Efficacy of Treatments for Opioid-Induced Constipation: Systematic Review and
      Meta-analysis.
AB  - BACKGROUND & AIMS: Opioid-induced constipation (OIC) is a common problem in
      patients on chronic opioid therapy for cancer-related and non-cancer-related
      pain. Approved treatments for OIC are methylnaltrexone, naloxone, naloxegol,
      alvimopan, naldemedine, and lubiprostone. Since a meta-analysis performed in
      2014, 2 new agents have been approved by the Food and Drug Administration for
      treatment of OIC (naloxegol and naldemedine). METHODS: We conducted a search of
      the medical literature following the protocol outlined in the Cochrane Handbook
      for systematic review. We searched MEDLINE, EMBASE, EMBASE Classic, Web of
      Science, and the Cochrane Central Register of Controlled Trials until March 2017
      to identify randomized controlled trials of peripheral MU-opioid-receptor
      antagonists (methylnaltrexone, naloxone, naloxegol, alvimopan, axelopran, or
      naldemedine), lubiprostone, or prucalopride. Response to therapy was extracted in
      a dichotomous assessment as an overall response to therapy. The effect of
      pharmacologic therapies was pooled and reported as a relative risk (RR) of
      failure to respond to the treatment drug, with 95% CIs. RESULTS: We included 27
      placebo-controlled trials in our meta-analysis (23 trials evaluated MU-opioid
      receptor antagonists, 3 trials evaluated lubiprostone, and 1 trial evaluated
      prucalopride). In these trials, 5390 patients received a drug and 3491 received a
      placebo. Overall, MU-opioid-receptor antagonists, lubiprostone, and prucalopride
      were superior to placebo for the treatment of OIC, with a RR of failure to
      respond to therapy of 0.70 (95% CI, 0.64-0.75) and an overall number needed to
      treat of 5 (95% CI, 4-7). When restricted to only Food and Drug Administration
      approved medications for OIC, the RR of failure to respond to therapy was 0.69
      (95% CI, 0.62-0.77), with a number needed to treat of 5 (95% CI, 4-7).
      Sensitivity analyses and meta-regression performed to account for heterogeneity
      showed that treatment was more likely to be effective in study populations taking
      higher doses of opiates at baseline or refractory to laxatives. Study duration
      and prespecified primary outcome did not affect the RR of failure. Participants
      who received MU-opioid-receptor antagonists were significantly more likely to
      have diarrhea, abdominal pain, nausea, or vomiting than patients who received
      placebo. CONCLUSIONS: In a systematic review and meta-analysis, we found MU
      opioid-receptor antagonists to be safe and effective for the treatment of OIC.
      Prescription-strength laxatives (prucalopride, lubiprostone) are slightly better
      than placebo in reducing OIC.

PMID- 29374617
TI  - Efficacy of Medical Therapies for Fistulizing Crohn's Disease: Systematic Review
      and Meta-analysis.
AB  - BACKGROUND & AIMS: Fistulas are debilitating complications of Crohn's disease
      (CD) that affect up to 50% of patients. We conducted a systematic review and meta
      analysis of randomized controlled trials to assess the efficacy of treatments for
      fistulizing CD. METHODS: We searched publication databases from inception through
      December 13, 2016 for trials comparing the efficacy of a therapeutic agent
      (single or combination) with placebo or another active therapy in adult patients
      with any form of fistulizing CD. The Cochrane risk of bias tool was used to
      assess the methodological quality of trials; the overall quality of evidence was
      evaluated using GRADE. Primary outcomes included induction and maintenance of
      fistula response and remission. Pooled risk ratios (RRs) and 95% CIs were
      calculated for each outcome. RESULTS: We analyzed data from 27 trials; most
      studies (21/27) focused on patients with perianal fistulizing CD. We found
      moderate-quality evidence to support the efficacy of tumor necrosis factor (TNF)
      antagonists (RR, 2.01; 95% CI, 1.36-2.97), particularly infliximab, ustekinumab
      (RR, 1.77; 95% CI, 0.93-3.37), and mesenchymal stem cell therapy (RR, 1.31; 95%
      CI, 0.98-1.73) for induction of fistula remission. We found low-quality evidence
      for the efficacy of vedolizumab and immunosuppressives. There was also low
      quality evidence to support the efficacy of combination therapy with TNF
      antagonists and antibiotics vs a TNF antagonist alone. CONCLUSION: In a
      systematic review and meta-analysis of 27 controlled trials, we found TNF
      antagonists to be effective for induction and maintenance of perianal fistula
      response and remission. There are few data on the effects on internal fistulae.
      Further studies are needed, particularly for ustekinumab, vedolizumab, and stem
      cell therapies, in patients with fistulizing CD.

PMID- 29374618
TI  - Does Computed Tomography-Based Virtual Colonoscopy Improve the Accuracy of
      Preoperative Assessment Based on Magnetic Resonance Imaging in Women Managed for
      Colorectal Endometriosis?
AB  - STUDY OBJECTIVE: To evaluate whether combining computed tomography-based virtual
      colonoscopy (CTC) with magnetic resonance imaging (MRI) improves preoperative
      assessment of colorectal endometriosis. DESIGN: Retrospective study using
      prospectively recorded data (Canadian Task Force classification II-2). SETTING:
      University tertiary referral center. PATIENTS: Seventy-one women treated for
      colorectal endometriosis managed between June 2015 and May 2016. INTERVENTIONS:
      Patients included in our study underwent colorectal surgery for deep
      endometriosis infiltrating the rectum or the sigmoid colon and had preoperative
      assessment using MRI and CTC. To establish the correlation between preoperative
      and intraoperative findings, the concordance kappa index was used. MEASUREMENTS
      AND MAIN RESULTS: Preoperative data provided by MRI, CTC, and a combination of
      both were compared with intraoperative findings. All 71 patients had a total of
      105 endometriotic intestinal lesions intraoperatively confirmed. Some 71.2% of
      rectal nodules and 60.0% of sigmoid nodules infiltrated the muscularis propria of
      the intestinal wall, with most infiltrating between 25% and 50% of the rectal
      circumference; 73% of rectal nodules and 96% of sigmoid nodules led to varying
      degrees of stenosis. The concordance between intraoperative and preoperative
      findings concerning the presence of rectal nodules was high, at .88 when
      associating CTC with MRI, whereas each imaging technique taken individually
      provided lower concordance coefficients. In our study 80.3% of patients underwent
      the procedure that had been preoperatively planned. CONCLUSION: Our study
      suggests that associating MRI with CTC leads to improved accuracy in preoperative
      assessment of colorectal endometriosis and in subsequent preoperative choice of
      surgical procedures on the digestive tract.

PMID- 29374619
TI  - Incisional Outcomes of Umbilical vs Suprapubic Mini-laparotomy for Tissue
      Extraction: A Retrospective Cohort Study.
AB  - STUDY OBJECTIVE: To compare outcomes following umbilical minilaparotomy and
      suprapubic minilaparotomy for tissue extraction. DESIGN CLASSIFICATION:
      Retrospective cohort study (Canadian Task Force classification II-2). SETTING:
      Two large academic medical centers. PATIENTS: Women who underwent a
      minilaparotomy for tissue extraction following a laparoscopic hysterectomy or
      myomectomy between 2014 and 2016. INTERVENTIONS: Umbilical or suprapubic
      minilaparotomy for tissue extraction. MEASUREMENTS AND MAIN RESULTS: A total of
      374 women underwent laparoscopic hysterectomy or myomectomy with minilaparotomy,
      including 289 (77.3%) with an umbilical minilaparotomy and 85 (22.7%) with a
      suprapubic minilaparotomy. The 2 groups were similar in terms of age, body mass
      index, parity, surgical history, procedure type, surgical approach, and surgical
      indication. The size of the minilaparotomy incision and the specimen weight were
      significantly smaller in the umbilical minilaparotomy group (mean, 3.3 +/- 0.8 cm
      vs 4.2 +/- 0.6 cm [p < .001] and 472.6 +/- 357.1 g vs 683.0 +/- 475.7 g [p <
      .001], respectively). Two women in the suprapubic minilaparotomy group sustained
      a bladder injury during creation of the incision. There were no other
      complications related to the minilaparotomy in either group. Postoperative
      outcomes related to the minilaparotomy incision were compiled using the medical
      record and a follow-up survey. Of the 374 women in this cohort, 163 responded to
      a detailed survey about their minilaparotomy incision (response rate, 43.5%).
      With regard to the minilaparotomy, 52.7% of women reported incisional symptoms;
      25.9% had increased pain at the incision, 8.3% had an incisional infection, and
      2.7% reported an incisional hernia. There was no significant between-group
      difference in incisional outcomes; however nearly 3 times as many women in the
      umbilical minilaparotomy group reported concerns about incisional hernia (3.1% vs
      1.2%; p = .833). These findings were maintained in a multivariable logistic
      regression analysis. No patient or procedure characteristics were significantly
      associated with the development of hernia. CONCLUSION: There were no significant
      difference in incisional symptoms, pain, or infection following umbilical
      minilaparotomy vs a suprapubic minilaparotomy for tissue extraction. Although not
      statistically significant, the rate of incisional hernia was higher at the
      umbilical site compared with the suprapubic site.

PMID- 29374620
TI  - Pain is an Independent Risk Factor for Failed Global Endometrial Ablation.
AB  - STUDY OBJECTIVE: To determine whether pain, as part of an indication for global
      endometrial ablation, is an independent risk factor for failure. DESIGN:
      Retrospective cohort study (Canadian Task Force classification II-2). SETTING:
      Academic-affiliated community hospital. PATIENTS: Women undergoing global
      endometrial ablation with radiofrequency ablation (RFA), hydrothermablation
      (HTA), or uterine balloon ablation (UBA) between January 2003 and December 2015.
      INTERVENTIONS: Procedure failure was defined as subsequent hysterectomy after the
      index ablation. MEASUREMENTS AND MAIN RESULTS: A total of 5818 women who
      underwent an endometrial ablation were identified, including 3706 with RFA
      (63.7%), 1786 with HTA (30.7%), and 326 with UBA (5.6%). Of the 5818 ablations,
      437 (7.5%) involved pain (i.e., pelvic pain, dysmenorrhea, dyspareunia, lower
      abdominal pain, endometriosis, or adenomyosis) before ablation, along with
      abnormal uterine bleeding. Pain as part of the preoperative diagnoses before
      endometrial ablation was a significant risk factor for subsequent hysterectomy
      compared with all other diagnoses (19.2% vs 13.5%; p = .001). Consistent with
      previous studies, women who underwent ablation at an older age were less likely
      to fail, which held true even when one of the indications for ablation was
      related to pain (odds ratio, 0.96/year; 95% confidence interval, 0.95-0.97). When
      the pathology reports of women who underwent a hysterectomy were examined, women
      in the pain group had lower rates of adenomyosis than women without pain (38.1%
      vs 50.1%; p = .04). However, there was a trend toward a higher rate of
      endometriosis on pathology reports (14.3% vs 8.7%; p = .09) and even higher rates
      of visualized endometriosis identified by operative reports in women who had pain
      before their ablation (42.9% vs 15.8%; p < .001). Patients who had pain before
      their ablation were less likely to have myomas/polyps (p = .01). CONCLUSION:
      Pelvic pain before global endometrial ablation is an independent risk factor for
      failure.

PMID- 29374621
TI  - Response to Sheehan et al's 'In defence of governance: ethics review and social
      research'.
AB  - This response welcomes Sheehan et al's discussion of the criticisms that have
      been made of mandatory, pre-emptive ethics regulation and their outline of a
      philosophical rationale for it. However, it is argued that they misrepresent some
      of the key criticisms and fail to provide any effective response to them.

PMID- 29374622
TI  - Prescribing in paediatric obesity: methods to improve dosing safety in weight
      based dose calculations.

PMID- 29374623
TI  - GMC confidentiality guidance 2017.

PMID- 29374624
TI  - What factors affect adherence to medicines?

PMID- 29374625
TI  - Authors' reply: 'Response to: 'Psychosocial job stressors and suicidality: a meta
      analysis and systematic review' by Milneret al'.

PMID- 29374626
TI  - 4CMenB and post-immunisation fever: an emerging hot topic.

PMID- 29374627
TI  - Morbidity and mortality with early pulmonary haemorrhage in preterm neonates.
AB  - OBJECTIVE: There are no large studies evaluating pulmonary haemorrhage (PH) in
      premature infants. We sought to quantify the clinical characteristics,
      morbidities and mortality associated with early PH. DESIGN: Data were abstracted
      from the Pediatrix Clinical Data Warehouse, a large de-identified data set. For
      incidence calculations, we included infants from 340 Pediatrix United States
      Neonatal Intensive Care Units from 2005 to 2014 without congenital anomalies.
      Infants <28 weeks' gestation with PH within 7 days of birth were then matched
      with two controls for birth weight, gestational age, gender, antenatal steroid
      exposure, day of life 0 or 1 intubation and multiple gestation. RESULTS: From 596
      411 total infants, we identified 2799 with a diagnosis of PH. Peak incidence was
      86.9 cases per 1000 admissions for neonates born at 24 weeks' gestation. We then
      identified 1476 infants <28 weeks' gestation with an early PH diagnosis at <=7
      days of age of which 1363 (92.3%) were successfully matched. Patients with early
      PH had significantly higher exposure to poractant alfa (35.4% vs 28%), diagnosis
      of shock (63.7% vs 51%) and grade IV intraventricular haemorrhage (20.8% vs 6%).
      Patients with PH also had significantly higher mortality rates at 7 days of age
      (40.6% vs 18.9%), 30 days of age (54% vs 28.8%) and prior to discharge (56.9% vs
      33.7). CONCLUSION: In this large cohort of premature infants, we found PH to be
      common among the most premature babies. Early PH was associated with significant
      morbidity and mortality in excess of 50%. A renewed focus on the underlying
      pathophysiology and prevention of PH is warranted.

PMID- 29374628
TI  - Radiological feature of colonic atresia.

PMID- 29374630
TI  - Non-parenchymal TREM-2 protects the liver from immune-mediated hepatocellular
      damage.
AB  - OBJECTIVE: Liver injury impacts hepatic inflammation in part via Toll-like
      receptor (TLR) signalling. Triggering receptor expressed on myeloid cells 2 (TREM
      2) modulates TLR4-mediated inflammation in bone marrow (BM)-derived macrophages
      but its function in liver injury is unknown. Here we hypothesised that the anti
      inflammatory effects of TREM-2 on TLR signalling may limit hepatic injury.
      DESIGN: TREM-2 expression was analysed in livers of humans with various forms of
      liver injury compared with control individuals. Acute and chronic liver injury
      models were performed in wild type and Trem-2-/- mice. Primary liver cells from
      both genotypes of mice were isolated for in vitro experiments. RESULTS: TREM-2
      was expressed on non-parenchymal hepatic cells and induced during liver injury in
      mice and man. Mice lacking TREM-2 exhibited heightened liver damage and
      inflammation during acute and repetitive carbon tetrachloride and acetaminophen
      (APAP) intoxication, the latter of which TREM-2 deficiency was remarkably
      associated with worsened survival. Liver damage in Trem-2-/- mice following
      chronic injury and APAP challenge was associated with elevated hepatic lipid
      peroxidation and macrophage content. BM transplantation experiments and cellular
      reactive oxygen species assays revealed effects of TREM-2 in the context of
      chronic injury depended on both immune and resident TREM-2 expression. Consistent
      with effects of TREM-2 on inflammation-associated injury, primary hepatic
      macrophages and hepatic stellate cells lacking TREM-2 exhibited augmented TLR4
      driven proinflammatory responses. CONCLUSION: Our data indicate that by acting as
      a natural brake on inflammation during hepatocellular injury, TREM-2 is a
      critical regulator of diverse types of hepatotoxic injury.

PMID- 29374631
TI  - Radial nerve injury following dry needling.
AB  - A 27-year-old secretary presented to an orthopaedic outpatients department with a
      1-month history of left wrist drop following dry needling. On insertion of a
      needle, she reported spasms in her left hand followed by a wrist drop. An MRI
      scan was normal. Electromyogram and nerve conduction studies showed a neuropraxia
      of the left radial nerve. She was referred to a hand therapist for splinting and
      intensive hand therapy; however, her symptoms remain unchanged.

PMID- 29374632
TI  - Cryptococcal meningitis in a daily cannabis smoker without evidence of
      immunodeficiency.
AB  - Cryptococcal meningitis is a life-threatening condition most commonly observed in
      immunocompromised individuals. We describe a daily cannabis smoker without
      evidence of immunodeficiency presenting with confirmed Cryptococcus neoformans
      meningitis. An investigation of cannabis samples from the patient's preferred
      dispensary demonstrated contamination with several varieties of Cryptococcus,
      including C. neoformans, and other opportunistic fungi. These findings raise
      concern regarding the safety of dispensary-grade cannabis, even in
      immunocompetent users.

PMID- 29374629
TI  - Cross-phenotype analysis of Immunochip data identifies KDM4C as a relevant locus
      for the development of systemic vasculitis.
AB  - OBJETIVE: Systemic vasculitides represent a heterogeneous group of rare complex
      diseases of the blood vessels with a poorly understood aetiology. To investigate
      the shared genetic component underlying their predisposition, we performed the
      first cross-phenotype meta-analysis of genetic data from different clinically
      distinct patterns of vasculitis. METHODS: Immunochip genotyping data from 2465
      patients diagnosed with giant cell arteritis, Takayasu's arteritis,
      antineutrophil cytoplasmic antibody-associated vasculitis or IgA vasculitis as
      well as 4632 unaffected controls were analysed to identify common susceptibility
      loci for vasculitis development. The possible functional consequences of the
      associated variants were interrogated using publicly available annotation data.
      RESULTS: The strongest association signal corresponded with an intergenic
      polymorphism located between HLA-DQB1 and HLA-DQA2 (rs6932517, P=4.16E-14,
      OR=0.74). This single nucleotide polymorphism is in moderate linkage
      disequilibrium with the disease-specific human leucocyte antigen (HLA) class II
      associations of each type of vasculitis and could mark them. Outside the HLA
      region, we identified the KDM4C gene as a common risk locus for vasculitides
      (highest peak rs16925200, P=6.23E-07, OR=1.75). This gene encodes a histone
      demethylase involved in the epigenetic control of gene expression. CONCLUSIONS:
      Through a combined analysis of Immunochip data, we have identified KDM4C as a new
      risk gene shared between systemic vasculitides, consistent with the increasing
      evidences of the crucial role that the epigenetic mechanisms have in the
      development of complex immune-mediated conditions.

PMID- 29374633
TI  - Desmoplastic fibroblastoma of the left upper arm.
AB  - An elderly female patient presented to the clinic with a several-week history of
      a mass in her left upper arm that was tender to the touch. The mass was initially
      thought to be a schwannoma of the left radial nerve based on imaging and was
      surgically removed. The pathology report revealed an uncommon diagnosis of
      desmoplastic fibroblastoma.

PMID- 29374634
TI  - Neurogenic pulmonary oedema secondary to vertebral artery dissection while
      playing tennis.
AB  - We present a case of a patient who developed vertebral artery dissection (VAD)
      while playing tennis and presented with neurogenic pulmonary oedema. The case
      highlights two important points: acute pulmonary oedema as an unusual presenting
      feature of VAD and VAD, an important cause of stroke in young people, as being
      associated with playing low-impact sports such as tennis. These associations,
      independent of each other, are under-recognised and can lead to a delay in
      diagnosis.

PMID- 29374635
TI  - Rare occurrence of eight-and-a-half syndrome as a clinically isolated syndrome.
AB  - Eight-and-a-half syndrome is a rare condition that is described as a combination
      of one-and-a-half syndrome and an ipsilateral facial nucleus lesion. We present a
      clinical case of occurrence of eight-and-a-half syndrome that was caused by a
      demyelinating lesion in the dorsal pontine tegmentum. A 44-year-old man presented
      to the hospital with a subacute onset of horizontal diplopia and left-sided
      facial weakness. MRI revealed a T2 hyperintense lesion in his dorsal pons, which
      was consistent with a demyelinating pathology. Treatment with intravenous
      steroids showed significant improvement in his symptoms. In our case, it occurred
      due to a suspected demyelinating lesion that was this patient's first and only
      demyelinating event, leaving him with a diagnosis of clinically isolated
      syndrome. His responsiveness to steroids represents the first case report of an
      adult patient presenting with an eight-and-a-half syndrome secondary to a
      suspected demyelinating pathology.

PMID- 29374636
TI  - Clostridium difficile enteritis: diffuse small bowel radiological changes in a
      patient with abdominal sepsis.
AB  - While imaging appearances of pseudomembranous colitis are commonly recognised,
      radiological manifestations of Clostridium difficile-associated enteritis are
      poorly understood which, combined with the rarity of this infection involving
      small bowel, makes establishing the correct diagnosis challenging. Therefore, in
      order to encourage awareness of readers, we present a case of C. difficile
      enteritis that manifested as abdominal sepsis complicating the postoperative
      period in a middle-aged woman with fistulating Crohn's disease and defunctioning
      ileostomy. Radiological appearances are described based on three consecutive CT
      studies performed 5 days prior to onset of symptoms, during the peak of
      enteritis, corresponding with the patient's clinical deterioration, and also 35
      days later following treatment and resolution.

PMID- 29374637
TI  - Emergency percutaneous transtracheal jet ventilation in a hypoxic cardiopulmonary
      resuscitation setting: a life-saving rescue technique.
AB  - (Un)anticipated difficult airway remains a challenge in anaesthesia. Percutaneous
      transtracheal jet ventilation has been shown to be an adequate technique for
      temporary oxygenation and ventilation and has been described as an acknowledged
      method in emergency settings of an unanticipated difficult airway. These
      emergency settings can be considered as low incidence high-risk situations. Both
      technical and non-technical skills should be trained regularly as education and
      simulation continues to play an important factor in patient safety. Furthermore,
      postoperative laryngeal oedema due to altered lymphatic drainage patterns must be
      considered as a possible mechanism of an upper airway obstruction in combination
      with a history of neck dissection and radiotherapy.

PMID- 29374638
TI  - Fluctuating hypercalcaemia caused by cavitary Mycobacterium bovis pulmonary
      infection.
AB  - Hypercalcaemia occurs in many granulomatous diseases. Among them, sarcoidosis and
      tuberculosis are the most common causes. Other causes include berylliosis,
      coccidioidomycosis, histoplasmosis, Crohn's disease, silicone-induced granulomas,
      cat-scratch disease, Wegener's granulomatosis and Pneumocystis carinii pneumonia.
      Hypercalcaemia in granulomatous disease occurs as a consequence of dysregulated
      production of 1,25-(OH)2 D3 (calcitriol) by activated macrophages in granulomas.
      Hypercalcaemia in patients with Mycobacterium tuberculosis infection has been
      reported in 0%-28% of cases. Uncultured bronchoalveolar lavage cells from
      patients with M. tuberculosis produce greater amounts of calcitriol compared with
      controls. Although Nayar et al described hypercalcaemia in a case of sepsis
      associated with intravesical Bacille Calmette Guerin therapy, there are no
      published reports describing hypercalcaemia in patients with pulmonary M. bovis
      infection. We describe a patient with M. bovis cavitary pulmonary infection with
      sustained hypercalcaemia that fluctuated and recurred repeatedly over the course
      of therapy, ultimately culminating in normalisation of serum calcium when therapy
      had led to cure. Treatment consisted of antituberculous therapy, oral
      corticosteroids and intravenous bisphosphonates with a favourable outcome.

PMID- 29374639
TI  - Sepsis Secondary to Bacteroides Fragilis Tubo-Ovarian Abscess Requiring
      Hysterectomy and Bilateral Salpingo-Oophorectomy.
AB  - A 45-year-old, G0P0 premenopausal woman was admitted for investigation of right
      lower quadrant pain, fever, leucocytosis and right adnexal abscess on CT. She was
      started on intravenous antibiotics and underwent CT-guided percutaneous drainage
      from which Bacteroides fragilis was cultured. A few days later, she had an
      exploratory laparotomy with incision and drainage. Once stabilised, she was
      discharged on intravenous antibiotics. She was followed outpatient and subsequent
      imaging demonstrated significant improvement of the abscess. After being
      asymptomatic for 3 months, she again presented to the emergency department with
      right lower quadrant abdominal pain, fever and leucocytosis. Two days later, she
      underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. She
      made a full recovery and began treatment with a herbal oestrogen derivative to
      prevent early menopause.

PMID- 29374640
TI  - Delayed diagnosis of dermal leiomyosarcoma mimicking keloid scar.
AB  - A 43-year-old man developed an abnormal scar 6 months following excision of a
      leiomyoma from his left shoulder. The scar was elevated, irregular in shape, pink
      red in colour, hard in consistency and it was extending beyond the margins of the
      original wound. A diagnosis of a keloid scar was considered and the patient was
      managed as such. He underwent a planned procedure for intralesional excision of
      the keloid scar. The histopathological examination showed a diagnosis of
      leiomyosarcoma. This case report presents a delayed diagnosis of dermal
      leiomyosarcoma mimicking a keloid scar. The patient subsequently underwent wider
      excision of the tumour with curative intention.

PMID- 29374641
TI  - Successful percutaneous drainage of pneumatoceles in an extremely low-birthweight
      infant.
AB  - Pneumatoceles are thin-walled, air-filled cystic lesions developing within the
      lung parenchyma. It used to be a relatively common entity in the presurfactant
      era when preterm babies were ventilated at an unacceptably high positive pressure
      for respiratory distress syndrome. Pneumatocele formation is a very rare
      complication of pneumonia in neonates. We here report a case of extremely low
      birthweight (ELBW) neonate who developed large bilateral pneumatoceles after
      staphylococcal pneumonia. Hereby, we present a case of an ELBW infant with
      bilateral massive pneumatoceles who underwent successful percutaneous catheter
      drainage to decompress these pneumatoceles.

PMID- 29374642
TI  - Hemiparesis in spontaneous spinal epidural haematoma: a potential stroke
      imitator.
AB  - Spontaneous spinal epidural haematoma (SSEH) is a rare condition that requires
      urgent surgical intervention in order to prevent permanent neurological deficit.
      SSEH commonly presents as a paraparesis or tetraparesis. SSEH presenting as a
      hemiparesis is less common and in such situations, it can be mistaken for a
      cerebrovascular accident (CVA). Thrombolytic or anticoagulant treatment for CVA
      can potentially worsen the neurological deficit. We report one such case of SSEH
      misdiagnosed as a CVA. Treatment with tissue plasminogen activator led to
      worsening of his condition. On a subsequent cervical spine MRI, an epidural
      haematoma extending from C3 to C5 was detected and treated with laminectomy and
      evacuation. Surgical intervention led to significant improvement from American
      Spinal Injury Association Scale (ASIA) B to ASIA E. Presence of clinical features
      such as Horner's syndrome, Brown-Sequard syndrome and the absence of cranial
      nerve palsies in acute hemiparesis are indicative of SSEH rather than CVA.

PMID- 29374643
TI  - Perimesencephalic and sulcal subarachnoid haemorrhage: an interesting
      presentation of posterior reversible encephalopathy syndrome.

PMID- 29374644
TI  - Don't put your foot in it: a case of talonavicular septic arthritis.
AB  - We present the second documented case of primary septic arthritis of the
      talonavicular joint. This patient had a number of medical comorbidities,
      including chronic widespread pain including the ipsilateral limb, which made
      diagnosis an even greater challenge. Although a clinical diagnosis, joint fluid
      aspiration remains the gold standard. Prompt surgical drainage with adjuvant
      antibiotic treatment is recommended, and management requires a multidisciplinary
      team approach. The aim of treatment is to avoid the sequelae of joint
      destruction, pain and foot deformity.

PMID- 29374645
TI  - Spontaneous calf haematoma in severe dengue.
AB  - We report a case of spontaneous calf muscle haematoma, formed during the recovery
      phase of dengue haemorrhagic fever, which, to the best of our knowledge, has
      never been encountered before. A 45-year-old man presented with features of
      severe dengue and got admitted to our intensive care unit. He was treated with
      intravenous fluid therapy and supportive measures, and gradually improved,
      initially. However, during the recovery phase, he suddenly developed painful left
      calf, which was found tender, hot and swollen on physical examination. Colour
      Doppler ultrasound revealed left calf haematoma. As the patient rapidly developed
      local compartmental syndrome, surgical evacuation of the haematoma followed by
      urgent fasciotomy was performed. He recovered without further complication and
      was discharged home. At follow-up after 2 months, he remained well.

PMID- 29374646
TI  - Simple surgical solution: scaphoid type congenital megalourethra.

PMID- 29374647
TI  - Acute retinal detachment induced by the Valsalva manoeuvre in morning glory disc
      anomaly.
AB  - We present a case in which a large, bullous, predominantly inferior, serous
      retinal detachment developed acutely after the Valsalva manoeuvre (from a
      coughing fit) in an eye with morning glory disc anomaly. We postulate that a
      rapid alteration in intracranial pressure was transmitted through the cavitary
      disc defect. This allowed a sudden influx of cerebrospinal fluid and/or liquefied
      vitreous into the subretinal space. This previously unreported case provides
      important evidence for the role of intracranial pressure fluctuations in the
      pathogenesis of macular schisis and neurosensory detachment secondary to optic
      disc cavitations.

PMID- 29374648
TI  - Secondary Omental Infarction in a Patient with a Hypercoagulable State.
AB  - Omental infarction is a rare cause of acute and non-specific abdominal pain. We
      report a case of a 46-year-old man who presented to the emergency room with right
      upper quadrant cramping pain that was of sudden onset. The patient's presentation
      was later diagnosed as an omental infarction, by an abdominal CT. After extensive
      work-up, it was revealed that the cause of the patient's omental infarction was
      secondary to a hypercoagulable state caused by antiphospholipid syndrome, based
      on his thrombophilia work-up. The patient was successfully managed conservatively
      and was started on lifelong anticoagulation. The patient was followed up with an
      abdominal CT after 2 months into therapy, which showed a decrease in the size of
      the omental infarction and a significant improvement in his state.

PMID- 29374649
TI  - Strangulated Spiegel's hernia mimicking ischaemic colitis: endoscopic diagnosis
      of a rare surgical emergency.

PMID- 29374650
TI  - Concurrent Pneumocystis jirovecii and pulmonary histoplasmosis in an undiagnosed
      HIV patient.
AB  - Concurrent Pneumocystis jirovecii (PJ) and pulmonary histoplasmosis (PHP) are
      rare in a single HIV individual. We present a challenging case of concomitant PJ
      and PHP in a young HIV individual. A 44-year-old man presented to the emergency
      department with progressive pulmonary symptoms. He was hypoxic with bilateral
      pulmonary opacities on chest radiograph. CT of the chest showed a geographical
      pattern of ground-glass attenuation. He started receiving intravenous antibiotics
      in addition to oral Bactrim for suspected PJ. He also began receiving
      itraconazole, given suspected PHP with recent bat-droppings exposure. HIV test
      was positive, though history was negative; the CD4 count was 5 cells/mm3 Later,
      he developed respiratory failure without clinical improvement. First
      bronchoalveolar lavage (BAL) failed to confirm opportunistic pathogens. Repeat
      BAL revealed PJ but no Histoplasma. Histoplasma antigens were positive,
      confirming histoplasmosis. The patient died despite aggressive treatment with
      intravenous Bactrim and amphotericin B.

PMID- 29374651
TI  - Clarithromycin as a steroid sparing agent for the management of infantile bullous
      pemphigoid.

PMID- 29374652
TI  - Chronic reactive arthritis associated with prostatitis caused by Neisseria
      meningitidis.

PMID- 29374653
TI  - Necrosis of the gastrocnemius muscle in microscopic polyangiitis.

PMID- 29374654
TI  - Oculocutaneous albinism with iridofundal coloboma.

PMID- 29374655
TI  - Symptomatic lower limb large vessel vasculitis presenting as fever of unknown
      origin diagnosed on FDG-PET/CT.

PMID- 29374656
TI  - A pneumothorax? When to look twice and treat once.

PMID- 29374657
TI  - Thread embedding acupuncture for musculoskeletal pain: a systematic review and
      meta-analysis protocol.
AB  - INTRODUCTION: Thread embedding acupuncture (TEA) is a special type of acupuncture
      that inserts certain medical threads (eg, catgut or polydioxanone) into
      subcutaneous tissue or muscles at specific points. Although TEA has been widely
      used for the treatment of musculoskeletal pain in Korea, China and Taiwan,
      evidence regarding its efficacy is lacking. The aim of this protocol is to
      evaluate the effectiveness and safety of TEA in the treatment of musculoskeletal
      pain, by conducting a systematic review and meta-analysis. METHODS AND ANALYSIS:
      The following 16 databases will be searched from their inception to 14 May 2017:
      MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the
      Cumulative Index to Nursing and Allied Health Literature, the Allied and
      Complementary Medicine Database, three Chinese database (China National Knowledge
      Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical
      Database and the Wanfang database) and eight Korean databases (Korean Medical
      Database, Korean Association of Medical Journal Editors, Korean Studies
      Information Service System, Korean National Assembly Digital Library, National
      Digital Science Library, Oriental Medicine Advanced Searching Integrated System,
      'Database Periodical Information Academic and Korean Traditional Knowledge
      Portal'). The WHO International Clinical Trials Registry Platform will also be
      searched to retrieve the recently completed studies.All randomised controlled
      studies in which TEA was used on specific points for the treatment of
      musculoskeletal pain will be included and no restrictions on language will be
      applied. The risk of bias of each study will be evaluated by the Cochrane risk of
      bias tool.Mean difference or standardised mean difference for continuous data and
      risk ratio for dichotomous data will be calculated with 95% CIs using a random
      effects model or a fixed effects model. Additional subgroup and sensitivity
      analyses will be conducted according to a predefined protocol. ETHICS AND
      DISSEMINATION: No ethical issues are predicted. The systematic review will be
      published in a peer-reviewed journal or conference presentation. These findings
      will summarise the current evidence of TEA for the treatment of musculoskeletal
      pain and may provide guidance for clinicians and patients to select TEA for
      musculoskeletal pain. PROSPERO REGISTRATION NUMBER: CRD42015019046.

PMID- 29374658
TI  - Protocol for Compass: a randomised controlled trial of primary HPV testing versus
      cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women
      aged 25-69 years living in Australia.
AB  - INTRODUCTION: Australia's National Cervical Screening Program (NCSP) currently
      recommends 2-year cytology in women aged 18-69 years. Following a review of the
      NCSP prompted by the implementation of human papillomavirus (HPV) vaccination,
      the programme will transition in 2017 to 5-year primary HPV screening with
      partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel
      experience for the renewed NCSP and the first prospectively randomised trial of
      primary HPV screening compared with cytology to be conducted in a population with
      high uptake of HPV vaccination. This protocol describes the main Compass trial,
      which commenced after a pilot study of ~5000 women completed recruitment. METHODS
      AND ANALYSIS: Women aged 25-69 years will be randomised at a 1:2 allocation to
      (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of
      low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial
      genotyping and referral of HPV16/18-positive women to colposcopy (intervention
      Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo
      secondary randomisation at a 1:1 allocation to either LBC or dual-stained
      (p16INK4a and Ki-67) cytology testing (dual-stained cytology). The primary
      outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical
      cancer) following a 5-year HPV exit testing round in both arms, in women
      randomised to the HPV arm versus women randomised to the LBC arm, based on an
      intention-to-treat analysis. The primary outcome will first be tested for non
      inferiority and if declared, the primary outcome will be tested for superiority.
      A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women
      in cohorts offered vaccination will be recruited, bringing the final sample size
      to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in
      screen-negative women, adjusted for censoring after CIN2+ treatment and
      hysterectomy. ETHICS AND DISSEMINATION: Approved by the Bellberry Ethics
      Committee (2014-11-592). Findings will be reported in peer-reviewed journals and
      presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT02328872; Pre
      results.

PMID- 29374659
TI  - Impact of hepatitis C virus infection on long-term mortality after acute
      myocardial infarction: a nationwide population-based, propensity-matched cohort
      study in Taiwan.
AB  - INTRODUCTION: The influence of hepatitis C virus (HCV) infection on long-term
      outcomes of patients with acute myocardial infarction (AMI) is unclear.
      Therefore, this study aimed to analyse the impact of HCV infection on 12-year
      mortality rates after AMI using data from the Taiwan National Health Insurance
      Research Database (NHIRD). METHODS: NHIRD data for approximately 23 000 000
      patients between January 2000 and December 2012 were analysed. A total of 186 112
      cases of first AMI admission were identified. A total of 4659 patients with HCV
      infection not receiving interferon therapy were enrolled and divided into those
      with (n=107) or without (n=4552) cirrhosis. Using one-to-one matching, 4552
      matched controls were included in the final analysis. RESULTS: The 12-year
      mortality rate was significantly higher in patients with AMI with HCV infection
      and cirrhosis than in those with HCV infection but without cirrhosis (P<0.0001)
      or controls (P<0.0001). Patients with HCV infection but without cirrhosis had
      significantly higher long-term mortality rates than the matched controls
      (P<0.0001). The HR for mortality was higher in patients with HCV infection (HR
      1.12; 95% CI 1.06 to 1.18). HCV influenced outcomes among the subgroups of
      patients who were male (HR 1.15) and those who had hypertension (HR 1.14).
      CONCLUSIONS: HCV infection influenced the 12-year mortality rates of patients
      with AMI, especially those who were male and those who had hypertension.
      Cirrhosis further increased the long-term mortality rates of patients with AMI
      with HCV infection.

PMID- 29374660
TI  - Blood-based biomarkers of cancer-related cognitive impairment in non-central
      nervous system cancer: protocol for a scoping review.
AB  - INTRODUCTION: Cancer-related cognitive impairment (CRCI) can have detrimental
      effects on quality of life, even among patients with non-central nervous system
      (CNS) cancers. Several studies have been conducted to explore different markers
      associated with CRCI to understand its pathobiology. It is proposed that the
      underlying mechanisms of CRCI are related to a cascade of physiological adaptive
      events in response to cancer and/or treatment. Hence, peripheral blood would be a
      logical source to observe and identify these physiological events. This paper
      outlines the protocol for a scoping review being conducted to summarise the
      extant literature regarding blood-based biomarkers of CRCI among patients with
      non-CNS cancer. METHODS/ANALYSIS: Methods will be informed by the updated
      guidelines of Arksey and O'Malley. The systematic search for literature will
      include electronic databases, handsearching of key journals and reference lists,
      forward citation tracking and consultation with content experts. Study selection
      will be confirmed by duplicate review and calculation of inter-rater reliability.
      Data to be charted will include study design, sample size, cancer and treatment
      characteristics, demographic characteristics, cognitive variable/s and biomarkers
      assessed, associations between cognitive functioning and biomarkers (including
      statistics used), and rigour in biomarker sample collection and processing.
      Results will be presented through: (1) a descriptive numerical summary of
      studies, including a flow diagram based on the Preferred Reporting Items for
      Systematic Reviews and Meta-analyses statement, (2) a list of blood-based
      biomarkers associated with CRCI and (3) a narrative overview developed through
      collaboration among the research team and consultation with content experts.
      DISSEMINATION: The findings of this review will highlight current directions and
      gaps in the current body of evidence that may lead to improved rigour in future
      CRCI investigations. The dissemination of this work will be facilitated through
      the involvement of clinicians and researchers on the research team, an external
      consultation process and the presentation of the results through scholarly
      publication and presentation.

PMID- 29374661
TI  - Multicentre validation of a sepsis prediction algorithm using only vital sign
      data in the emergency department, general ward and ICU.
AB  - OBJECTIVES: We validate a machine learning-based sepsis-prediction algorithm
      (InSight) for the detection and prediction of three sepsis-related gold
      standards, using only six vital signs. We evaluate robustness to missing data,
      customisation to site-specific data using transfer learning and generalisability
      to new settings. DESIGN: A machine-learning algorithm with gradient tree
      boosting. Features for prediction were created from combinations of six vital
      sign measurements and their changes over time. SETTING: A mixed-ward
      retrospective dataset from the University of California, San Francisco (UCSF)
      Medical Center (San Francisco, California, USA) as the primary source, an
      intensive care unit dataset from the Beth Israel Deaconess Medical Center
      (Boston, Massachusetts, USA) as a transfer-learning source and four additional
      institutions' datasets to evaluate generalisability. PARTICIPANTS: 684 443 total
      encounters, with 90 353 encounters from June 2011 to March 2016 at UCSF.
      INTERVENTIONS: None. PRIMARY AND SECONDARY OUTCOME MEASURES: Area under the
      receiver operating characteristic (AUROC) curve for detection and prediction of
      sepsis, severe sepsis and septic shock. RESULTS: For detection of sepsis and
      severe sepsis, InSight achieves an AUROC curve of 0.92 (95% CI 0.90 to 0.93) and
      0.87 (95% CI 0.86 to 0.88), respectively. Four hours before onset, InSight
      predicts septic shock with an AUROC of 0.96 (95% CI 0.94 to 0.98) and severe
      sepsis with an AUROC of 0.85 (95% CI 0.79 to 0.91). CONCLUSIONS: InSight
      outperforms existing sepsis scoring systems in identifying and predicting sepsis,
      severe sepsis and septic shock. This is the first sepsis screening system to
      exceed an AUROC of 0.90 using only vital sign inputs. InSight is robust to
      missing data, can be customised to novel hospital data using a small fraction of
      site data and retains strong discrimination across all institutions.

PMID- 29374662
TI  - Evaluating sickness absence duration by musculoskeletal and mental health issues:
      a retrospective cohort study of Scottish healthcare workers.
AB  - OBJECTIVES: Sickness absence (SA) among healthcare workers is associated with
      occupational and non-occupational risk factors and impacts employee health,
      healthcare delivery and patient health. At the same time, healthcare is one of
      the employment sectors with the highest rates of work-related ill health in the
      UK. Musculoskeletal (MSK) and mental health (MH) issues are leading causes of SA,
      but there is a lack of research on how certain MSK/MH conditions impact on SA
      duration. The study aim is to determine differences in SA duration by MH and MSK
      disorders in healthcare employees. METHODS: Survival analyses were used to
      estimate SA duration due to MSK and MH problems over 6 years, and Cox's
      proportional hazards models to determine the HRs of returning to work, using a
      bespoke Scottish health board database with over 53 000 SA events. SA duration
      and time to return-to-work (RTW) were estimated for employees by age, gender, job
      and health conditions. RESULTS: MSK and MH conditions accounted for 27% and 6% of
      all SA events and 23.7% and 19.5% of all days lost, respectively. Average SA
      duration was 43.5 days for MSK and 53.9 days for MH conditions. For MSK
      conditions, employees with low back or neck pain had the fastest RTW (median P50:
      7 days), whereas employees absent due to depression took the longest (P50: 54
      days). The most influential sociodemographic variables affecting RTW were age,
      gender and job category. CONCLUSIONS: Using a unique and rich database, we found
      significant differences in SA duration by presenting condition in healthcare
      workers. MH conditions, and depression specifically, accounted for the most
      working days' absence. Significant variations in duration were also observed for
      MSK conditions. Our findings can inform public health practitioners and
      healthcare managers of the most significant factors impacting MSK-related and MH
      related SA to develop and implement tailored and targeted workplace
      interventions.

PMID- 29374663
TI  - Cross-sectional study assessing the addition of contrast sensitivity to visual
      acuity when testing for fitness to drive.
AB  - OBJECTIVES: The aim of this study is to quantify the importance of loss of
      contrast sensitivity (CS) and its relationship to loss of visual acuity (VA),
      driving restrictions and daytime, on-road driving evaluations in drivers aged
      70+. DESIGN: A predictive cross-sectional study. SETTING: Volunteer participants
      to a drivers' refresher course for adults aged 70+ delivered by the Swiss
      Automobile Club in western Switzerland from 2011 to 2013. PARTICIPANTS: 162
      drivers, male and female, aged 70 years or older. CLINICAL PREDICTORS: We used a
      vision screener to estimate VA and the The Mars Letter Contrast Sensitivity Test
      to test CS. OUTCOMES: We asked drivers to report whether they found five driving
      restrictions useful for their condition; restrict driving to known roads, avoid
      driving on highways, avoid driving in the dark, avoid driving in dense traffic
      and avoid driving in fog. All participants also underwent a standardised on-road
      evaluation carried out by a driving instructor. RESULTS: Moderate to severe loss
      of CS for at least one eye was frequent (21.0% (95% CI 15.0% to 28.1%)) and often
      isolated from a loss of VA (11/162 cases had a VA >=0.8 decimal and a CS of <=1.5
      log(CS); 6.8% (95% CI 3.4% to 11.8%)). Drivers were more likely (R2=0.116,
      P=0.004) to report a belief that self-imposed driving restrictions would be
      useful if they had reduced CS in at least one eye. Daytime evaluation of driving
      performance seems limited in its ability to correctly identify difficulties
      related to CS loss (VA: R2=0.004, P=0.454; CS: R2=0.006, P=0.332). CONCLUSION: CS
      loss is common for older drivers. Screening CS and referring for cataract surgery
      even in the absence of VA loss could help maintain mobility. Reduced CS and
      moderate reduction of VA were both poor predictors of daytime on-road driving
      performances in this research study.

PMID- 29374664
TI  - Students' satisfaction and perceived impact on knowledge, attitudes and skills
      after a 2-day course in scientific writing: a prospective longitudinal study in
      Spain.
AB  - OBJECTIVES: This study aimed to determine students' satisfaction with a 2-day
      course on scientific writing in health sciences and to assess their perceptions
      of the long-term impact on their knowledge, attitudes and skills. SETTING: 27
      iterations of a 2-day course on writing and publishing scientific articles in
      health sciences. PARTICIPANTS: 741 students attending the 27 courses. DESIGN:
      Prospective longitudinal study. PRIMARY AND SECONDARY OUTCOME MEASURES:
      Immediately after each course, students completed a first questionnaire, rating
      their satisfaction with different aspects of the classroom sessions on a Likert
      scale (0-5). Approximately 2 years after the course, students completed a follow
      up questionnaire, using a Likert scale (0-4) to rate their knowledge, skills and
      attitudes in relation to scientific writing before and after attending the
      course. RESULTS: 741 students (70% women) participated in the 27 iterations of
      the course; 568 (76.8%) completed the first questionnaire and 182 (24.6%)
      completed the follow-up questionnaire. The first questionnaire reflected high
      overall satisfaction (mean score, 4.6). In the second questionnaire, students
      reported that the course had improved their knowledge (mean improvement: 1.6; 95%
      CI 1.6 to 1.7), attitudes (mean improvement: 1.3; 95% CI 1.2 to 1.4) and skills
      (mean improvement: 1.4; 95% CI 1.3 to 1.4) related to writing and publishing
      scientific papers. Most respondents (n=145, 79.7%) had participated in drafting a
      scientific paper after the course; in this subgroup, all the specific writing
      skills assessed in the second questionnaire significantly improved. CONCLUSIONS:
      Students were satisfied with the format and the contents of the course, and those
      who responded to the follow-up survey considered that the course had improved
      their knowledge, attitudes and skills in relation to scientific writing and
      publishing. Courses are particularly important in countries without strong
      traditions in scientific publication.

PMID- 29374665
TI  - Needs of informal caregivers across the caregiving course in amyotrophic lateral
      sclerosis: a qualitative analysis.
AB  - OBJECTIVES: Amyotrophic lateral sclerosis (ALS), also known as motor neuron
      disease (MND), is a debilitating terminal condition. Informal caregivers are key
      figures in ALS care provision. The physical, psychological and emotional impact
      of providing care in the home requires appropriate assistance and support. The
      objective of this analysis is to explore the needs of informal ALS caregivers
      across the caregiving course. DESIGN: In an open-ended question as part of a
      semistructured interview, caregivers were asked what would help them in their
      role. Interviews took place on three occasions at 4-month to 6-month intervals.
      Demographic, burden and quality of life data were collected, in addition to the
      open-ended responses. We carried out descriptive statistical analysis and
      thematic analysis of qualitative data. SETTING AND PARTICIPANTS: Home interviews
      at baseline (n=81) and on two further occasions (n=56, n=41) with informal
      caregivers of people with ALS attending the National ALS/MND Clinic at Beaumont
      Hospital, Dublin, Ireland. RESULTS: The majority of caregivers were family
      members. Hours of care provided and caregiver burden increased across the
      interview series. Thematic analysis identified what would help them in their
      role, and needs related to external support and services, psychological-emotional
      factors, patient-related behaviours, a cure and 'nothing'. Themes were
      interconnected and their prevalence varied across the interview time points.
      CONCLUSION: This study has shown the consistency and adaptation in what
      caregivers identified as helpful in their role, across 12-18 months of a
      caregiving journey. Support needs are clearly defined, and change with time and
      the course of caregiving. Caregivers need support from family, friends and
      healthcare professionals in managing their tasks and the emotional demands of
      caregiving. Identifying the specific needs of informal caregivers should enable
      health professionals to provide tailored supportive interventions.

PMID- 29374666
TI  - Quality of life, sleep and rheumatoid arthritis (QUASAR): a protocol for a
      prospective UK mHealth study to investigate the relationship between sleep and
      quality of life in adults with rheumatoid arthritis.
AB  - INTRODUCTION: People with rheumatoid arthritis (RA) frequently report reduced
      health-related quality of life (HRQoL), the impact one's health has on physical,
      emotional and social well-being. There are likely numerous causes for poor HRQoL,
      but people with RA have identified sleep disturbances as a key contributor to
      their well-being. This study will identify sleep/wake rhythm-associated
      parameters that predict HRQoL in patients with RA. METHODS AND ANALYSIS: This
      prospective cohort study will recruit 350 people with RA, aged 18 years or older.
      Following completion of a paper-based baseline questionnaire, participants will
      record data on 10 symptoms including pain, fatigue and mood two times a day for
      30 days using a study-specific mobile application (app). A triaxial accelerometer
      will continuously record daytime activity and estimate evening sleep parameters
      over the 30 days. Every 10 days following study initiation, participants will
      complete a questionnaire that measures disease specific (Arthritis Impact
      Measurement Scale 2-Short Form (AIMS2-SF)) and generic (WHOQOL-BREF) quality of
      life. A final questionnaire will be completed at 60 days after entering the
      study. The primary outcomes are the AIMS2-SF and WHOQOL-BREF. Structural equation
      modelling and latent trajectory models will be used to examine the relationship
      between sleep/wake rhythm-associated parameters and HRQoL, over time. ETHICS AND
      DISSEMINATION: Results from this study will be disseminated at regional and
      international conferences, in peer-reviewed journals and Patient and Public
      Engagement events, as appropriate.

PMID- 29374667
TI  - Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a
      randomised controlled trial.
AB  - INTRODUCTION: Epidural analgesia provides an important synergistic method of pain
      control. In addition to reducing perioperative opioid consumption, the
      deliverance of analgesia into the epidural space, effectively creating a
      sympathetic blockade, has a multitude of additional potential benefits, from
      decreasing the incidence of postoperative delirium to reducing the development of
      persistent postsurgical pain (PPSP). Prior studies have also identified a
      correlation between the use of epidural analgesia and improved oncological
      outcomes and survival. The aim of this study is to evaluate the effect of
      epidural analgesia in pancreatic operations on immediate postoperative outcomes,
      the development of PPSP and oncological outcomes in a prospective, single-blind,
      randomised controlled trial. METHODS: The Epidurals in Pancreatic Resection
      Outcomes (E-PRO) study is a prospective, single-centre, randomised controlled
      trial. 150 patients undergoing either pancreaticoduodenectomy or distal
      pancreatectomy will be randomised to receive an epidural bupivacaine infusion
      following anaesthetic induction followed by continued epidural bupivacaine
      infusion postoperatively in addition to the institutional standardised pain
      regimen of hydromorphone patient-controlled analgesia (PCA), acetaminophen and
      ketorolac (intervention group) or no epidural infusion and only the standardised
      postoperative pain regimen (control group). The primary outcome was the
      postoperative opioid consumption, measured in morphine or morphine-equivalents.
      Secondary outcomes include patient-reported postoperative pain numerical rating
      scores, trend and relative ratios of serum inflammatory markers (interleukin (IL)
      1beta, IL-6, tumour necrosis factor-alpha, IL-10), occurrence of postoperative
      delirium, development of PPSP as determined by quantitative sensory testing, and
      disease-free and overall survival. ETHICS AND DISSEMINATION: The E-PRO trial has
      been approved by the institutional review board. Recruitment began in May 2016
      and will continue until the end of May 2018. Dissemination plans include
      presentations at scientific conferences and scientific publications. TRIAL
      REGISTRATION NUMBER: NCT02681796.

PMID- 29374669
TI  - Trends and determinants of length of stay and hospital reimbursement following
      knee and hip replacement: evidence from linked primary care and NHS hospital
      records from 1997 to 2014.
AB  - OBJECTIVES: To measure changes in length of stay following total knee and hip
      replacement (TKR and THR) between 1997 and 2014 and estimate the impact on
      hospital reimbursement, all else being equal. Further, to assess the degree to
      which observed trends can be explained by improved efficiency or changes in
      patient profiles. DESIGN: Cross-sectional study using routinely collected data.
      SETTING: National Health Service primary care records from 1995 to 2014 in the
      Clinical Practice Research Datalink were linked to hospital inpatient data from
      1997 to 2014 in Hospital Episode Statistics Admitted Patient Care. PARTICIPANTS:
      Study participants had a diagnosis of osteoarthritis or rheumatoid arthritis.
      INTERVENTIONS: Primary TKR, primary THR, revision TKR and revision THR. PRIMARY
      OUTCOME MEASURES: Length of stay and hospital reimbursement. RESULTS: 10 260
      primary TKR, 10 961 primary THR, 505 revision TKR and 633 revision THR were
      included. Expected length of stay fell from 16.0 days (95% CI 14.9 to 17.2) in
      1997 to 5.4 (5.2 to 5.6) in 2014 for primary TKR and from 14.4 (13.7 to 15.0) to
      5.6 (5.4 to 5.8) for primary THR, leading to savings of L1537 and L1412,
      respectively. Length of stay fell from 29.8 (17.5 to 50.5) to 11.0 (8.3 to 14.6)
      for revision TKR and from 18.3 (11.6 to 28.9) to 12.5 (9.3 to 16.8) for revision
      THR, but no significant reduction in reimbursement was estimated. The estimated
      effect of year of surgery remained similar when patient characteristics were
      included. CONCLUSIONS: Length of stay for joint replacement fell substantially
      from 1997 to 2014. These reductions have translated into substantial savings.
      While patient characteristics affect length of stay and reimbursement, patient
      profiles have remained broadly stable over time. The observed reductions appear
      to be mostly explained by improved efficiency.

PMID- 29374671
TI  - Measurement properties of instruments assessing permanent functional impairment
      of the spine: a systematic review protocol.
AB  - INTRODUCTION: Permanent functional impairment (PFI) of the spine is a rating
      system used by compensation authorities, such as workers compensation boards, to
      establish an appropriate level of financial compensation for persistent loss of
      function. Determination of PFI of the spine is commonly based on the assessment
      of spinal movement combined with other measures of physical and functional
      impairments; however, the reliability and validity of the measurement instruments
      used for these evaluations have yet to be established. The aim of this study is
      to systematically review and synthesise the literature concerning measurement
      properties of the various and different instruments used for assessing PFI of the
      spine. METHODS: Three conceptual groups of terms (1) PFI, (2) spinal disorder and
      (3) measurement properties will be combined to search Medline, EMBASE, CINAHL,
      Web of Science, Scopus, PEDro, OTSeeker and Health and Safety Science Abstracts.
      We will examine peer-reviewed, full-text articles over the full available date
      range. Two reviewers will independently screen citations (title, abstract and
      full text) and perform data extraction. Included studies will be appraised as to
      their methodological quality using the COnsensus-based Standards for the
      selection of health Measurement INstruments criteria. Findings will be summarised
      and presented descriptively, with meta-analysis pursued as appropriate. ETHICS
      AND DISSEMINATION: This review will summarise the current level of evidence of
      measurement properties of instruments used for assessing PFI of the spine.
      Findings of this review may be applicable to clinicians, policy-makers, workers'
      compensation boards, other insurers and health and safety organisations. The
      findings will likely provide a foundation and direction for future research
      priorities for assessing spinal PFI. PROSPERO REGISTRATION NUMBER:
      CRD42017060390.

PMID- 29374668
TI  - Healthy Foundations Study: a randomised controlled trial to evaluate biological
      embedding of early-life experiences.
AB  - INTRODUCTION: Adverse early experiences are associated with long-lasting
      disruptions in physiology, development and health. These experiences may be
      'biologically embedded' into molecular and genomic systems that determine later
      expressions of vulnerability. Most studies to date have not examined whether
      preventive interventions can potentially reverse biological embedding. The Nurse
      Family Partnership (NFP) is an evidence-based intervention with demonstrated
      efficacy in improving prenatal health, parenting and child functioning. The
      Healthy Foundations Study is an innovative birth cohort which will evaluate the
      impact of the NFP on biological outcomes of mothers and their infants. METHODS
      AND ANALYSIS: Starting in 2013, up to 400 pregnant mothers and their newborns
      were recruited from the British Columbia Healthy Connections Project-a randomised
      controlled trial of the NFP, and will be followed to child aged 2 years. Women
      were recruited prior to 28 weeks' gestation and then individually randomised to
      receive existing services (comparison group) or NFP plus existing services
      (intervention group). Hair samples are collected from mothers at baseline and 2
      months post partum to measure physiological stress. Saliva samples are collected
      from infants during all visits for analyses of stress and immune function. Buccal
      swabs are collected from infants at 2 and 24 months to assess DNA methylation.
      Biological samples will be related to child outcome measures at age 2 years.
      ETHICS AND DISSEMINATION: The study received ethical approval from seven research
      ethics boards. Findings from this study will be shared broadly with the research
      community through peer-reviewed publications, and conference presentations, as
      well as seminars with our policy partners and relevant healthcare providers. The
      outcomes of this study will provide all stakeholders with important information
      regarding how early adversity may lead to health and behavioural disparities and
      how these may be altered through early interventions. TRIAL REGISTRATION NUMBER:
      NCT01672060; Pre-results.

PMID- 29374670
TI  - CARE CR-Cardiovascular and cardiorespiratory Adaptations to Routine Exercise
      based Cardiac Rehabilitation: a study protocol for a community-based controlled
      study with criterion methods.
AB  - INTRODUCTION: Cardiac rehabilitation (CR) reduces all-cause and cardiovascular
      mortality in patients with coronary heart disease (CHD). Much of this improvement
      has been attributed to the beneficial effects of structured exercise training.
      However, UK-based studies have not confirmed this. Improvements in survival and
      cardiovascular health are associated with concurrent improvements in
      cardiorespiratory fitness (CRF). It is therefore concerning that estimated CRF
      improvements resulting from UK-based CR are approximately one-third of those
      reported in international literature. Modest improvements in CRF suggest that UK
      CR exercise training programmes may require optimisation if long-term survival is
      to be improved. However, contemporary UK studies lack control data or use
      estimates of CRF change. Cardiovascular and cardiorespiratory Adaptations to
      Routine Exercise-based CR is a longitudinal, observational, controlled study
      designed to assess the short-term and long-term effect of CR on CRF, as well
      cardiovascular and cardiometabolic health. METHODS AND ANALYSIS: Patients will be
      recruited following referral to their local CR programme and will either
      participate in a routine, low-to-moderate intensity, 8-week (16 sessions)
      exercise-based CR programme or freely abstain from supervised exercise. Initial
      assessment will be conducted prior to exercise training, or approximately 2 weeks
      after referral to CR if exercise training is declined. Reassessment will coincide
      with completion of exercise training or 10 weeks after initial assessment for
      control participants. Participants will receive a final follow-up 12 months after
      recruitment. The primary outcome will be peak oxygen consumption determined using
      maximal cardiopulmonary exercise testing. Secondary outcomes will include changes
      in subclinical atherosclerosis (carotid intima-media thickness and plaque
      characteristics), body composition (dual X-ray absorptiometry) and
      cardiometabolic biomarkers. ETHICS AND DISSEMINATION: Ethical approval for this
      non-randomised controlled study has been obtained from the Humber Bridge NHS
      Research Ethics Committee-Yorkshire and the Humber on the 27th September 2013,
      (12/YH/0278). Results will be presented at national conferences and published in
      peer-reviewed journals.

PMID- 29374672
TI  - Study protocol for a cluster randomised controlled factorial design trial to
      assess the effectiveness and feasibility of reactive focal mass drug
      administration and vector control to reduce malaria transmission in the low
      endemic setting of Namibia.
AB  - INTRODUCTION: To interrupt malaria transmission, strategies must target the
      parasite reservoir in both humans and mosquitos. Testing of community members
      linked to an index case, termed reactive case detection (RACD), is commonly
      implemented in low transmission areas, though its impact may be limited by the
      sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria
      season is a cornerstone of vector control efforts. Despite their implementation
      in Namibia, a country approaching elimination, these methods have been met with
      recent plateaus in transmission reduction. This study evaluates the effectiveness
      and feasibility of two new targeted strategies, reactive focal mass drug
      administration (rfMDA) and reactive focal vector control (RAVC) in Namibia.
      METHODS AND ANALYSIS: This is an open-label cluster randomised controlled trial
      with 2*2 factorial design. The interventions include: rfMDA (presumptive
      treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic
      testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC.
      Factorial design also enables comparison of the combined rfMDA+RAVC intervention
      to RACD. Participants living in 56 enumeration areas will be randomised to one of
      four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered
      by index cases detected at health facilities, will be targeted to individuals
      residing within 500 m of an index. The primary outcome is cumulative incidence of
      locally acquired malaria detected at health facilities over 1 year. Secondary
      outcomes include seroprevalence, infection prevalence, intervention coverage,
      safety, acceptability, adherence, cost and cost-effectiveness. ETHICS AND
      DISSEMINATION: Findings will be reported on clinicaltrials.gov, in peer-reviewed
      publications and through stakeholder meetings with MoHSS and community leaders in
      Namibia. TRIAL REGISTRATION NUMBER: NCT02610400; Pre-results.

PMID- 29374673
TI  - Recommendations for successful sensory screening in older adults with dementia in
      long-term care: a qualitative environmental scan of Canadian specialists.
AB  - OBJECTIVES: This study aimed to identify screening tools, technologies and
      strategies that vision and hearing care specialists recommend to front-line
      healthcare professionals for the screening of older adults in long-term care
      homes who have dementia. SETTING: An environmental scan of healthcare
      professionals took place via telephone interviews between December 2015 and March
      2016. All interviews were audio recorded, transcribed, proofed for accuracy, and
      their contents thematically analysed by two members of the research team.
      PARTICIPANTS: A convenience sample of 11 professionals from across Canada
      specialising in the fields of vision and hearing healthcare and technology for
      older adults with cognitive impairment were included in the study. OUTCOME
      MEASURES: As part of a larger mixed-methods project, this qualitative study used
      semistructured interviews and their subsequent content analysis. RESULTS:
      Following a two-step content analysis of interview data, coded citations were
      grouped into three main categories: (1) barriers, (2) facilitators and (3) tools
      and strategies that do or do not work for sensory screening of older adults with
      dementia. We report on the information offered by participants within each of
      these themes, along with a summary of tools and strategies that work for
      screening older adults with dementia. CONCLUSIONS: Recommendations from sensory
      specialists to nurses working in long-term care included the need for improved
      interprofessional communication and collaboration, as well as flexibility,
      additional time and strategic use of clinical intuition and ingenuity. These
      suggestions at times contradicted the realities of service provision or the need
      for standardised and validated measures.

PMID- 29374675
TI  - Suicide bereavement: piloting a longitudinal study in Australia.
AB  - OBJECTIVES: The pilot study were (1) to test the technical and administrative
      feasibility of a full-scale study, including recruitment process, response and
      retention rate, questionnaire design for an investigation to improve
      understanding of the suicide bereavement processes compared with bereavement by
      sudden deaths and (2) to present the differences and changes in the main outcomes
      grief reactions of close relatives exposed to suicide and sudden death over 2
      years. DESIGN: A longitudinal prospective study comparing bereavement by suicide
      to other types of sudden deaths over time (6, 12 and 24 months). SETTING:
      Queensland, Australia. PARTICIPANTS: 25 suicide-bereaved and 15 sudden-death
      bereaved persons. OUTCOME MEASURES: Grief reactions (measured with the Grief
      Experience Questionnaire). RESULTS: The response rate was 52.1% in the suicide
      bereaved and 45.5% in the sudden-death group. There was a small number of
      dropouts, with the retention rate over 85% for both groups. Linear mixed
      modelling for repeated measures showed a significant group effect (higher in
      suicide bereaved) for total grief, responsibility, rejection and unique
      reactions. A significant time effect (reduction) was measured for total grief,
      somatic reactions, general grief reactions and search for explanation. One
      significant time and group interaction was measured; rejection showed a decline
      in suicide and an increase in sudden-death bereaved. CONCLUSIONS: The pilot study
      presented the appropriateness of the study methodology. This type of study has
      implications for counselling and treating people bereaved by suicide and for
      designing postvention activities.

PMID- 29374674
TI  - TEXT messages to improve MEDication adherence and Secondary prevention (TEXTMEDS)
      after acute coronary syndrome: a randomised clinical trial protocol.
AB  - BACKGROUND: Identifying simple, low-cost and scalable means of supporting
      lifestyle change and medication adherence for patients following a cardiovascular
      (CV) event is important. OBJECTIVE: The TEXTMEDS (TEXT messages to improve
      MEDication adherence and Secondary prevention) study aims to investigate whether
      a cardiac education and support programme sent via mobile phone text message
      improves medication adherence and risk factor levels in patients following an
      acute coronary syndrome (ACS). STUDY DESIGN: A single-blind, multicentre,
      randomised clinical trial of 1400 patients after an ACS with 12 months follow-up.
      The intervention group will receive multiple weekly text messages that provide
      information, motivation, support to adhere to medications, quit smoking (if
      relevant) and recommendations for healthy diet and exercise. The primary endpoint
      is the percentage of patients who are adherent to cardioprotective medications
      and the key secondary outcomes are mean systolic blood pressure (BP) and low
      density lipoprotein cholesterol. Secondary outcomes will also include total
      cholesterol, mean diastolic BP, the percentage of participants who are adherent
      to each cardioprotective medication class, the percentage of participants who
      achieve target levels of CV risk factors, major vascular events, hospital
      readmissions and all-cause mortality. The study will be augmented by formal
      economic and process evaluations to assess acceptability, utility and cost
      effectiveness. SUMMARY: The study will provide multicentre randomised trial
      evidence of the effects of a text message-based programme on cardioprotective
      medication adherence and levels of CV risk factors. ETHICS AND DISSEMINATION:
      Primary ethics approval was received from Western Sydney Local Health District
      Human Research Ethics Committee (HREC2012/12/4.1 (3648) AU RED HREC/13/WMEAD/15).
      Results will be disseminated via peer-reviewed publications and presentations at
      international conferences. TRIAL REGISTRATION NUMBER: ACTRN12613000793718; Pre
      results.

PMID- 29374676
TI  - Depressive symptoms and workplace-violence-related risk factors among
      otorhinolaryngology nurses and physicians in Northern China: a cross-sectional
      study.
AB  - OBJECTIVES: Workplace violence is relatively frequent among medical professionals
      who work in otorhinolaryngology units. This phenomenon reduces the quality of
      provided medical care and increases the incidence of depressive symptoms among
      physicians and nurses, seriously affecting their job satisfaction and work
      efficiency with a negative attitude towards providing treatment. Few existing
      studies have assessed workplace-violence-related factors associated with
      depressive symptoms among otorhinolaryngology physicians and nurses. METHODS: We
      conducted a cross-sectional study in grade A tertiary hospitals of Heilongjiang
      province in Northern China, to evaluate the occurrence and level of depressive
      symptoms among otorhinolaryngology physicians and nurses and to analyse the
      relationship between them and workplace-violence-related risk factors and
      demographic variables. RESULTS: Of all our participating professionals, (379
      otorhinolaryngologists and 273 nurses), 57.2% were found to have depressive
      symptoms, whereas, of the respondents who had suffered from physical violence,
      71.25% had depressive symptoms. Professionals with less than 1 year of
      experience, as well as professionals who more frequently worked alone, were more
      likely to suffer from depressive symptoms than their colleagues. CONCLUSIONS:
      This research addresses an emerging issue of clinical practice, and its results
      differ from those of previous studies; specifically, it indicates that the
      frequency of depressive symptoms among otorhinolaryngology physicians and nurses
      may be influenced by physical violence, the number of coworkers they have for
      more than half of their working hours and other workplace-violence-related
      factors. To reduce the depressive symptoms caused by workplace violence and
      improve the quality of medical services, medical institutions should implement
      effective measures to prevent the occurrence of physical violence, strengthen
      team cooperation ability and increase peer support.

PMID- 29374677
TI  - Maternal and birth cohort studies in the Gulf Cooperation Council countries:
      protocol for a systematic review and narrative evaluation.
AB  - INTRODUCTION: Cohort studies have revealed that genetic, socioeconomic,
      communicable and non-communicable diseases, and environmental exposures during
      pregnancy may influence the mother and her pregnancy, birth delivery and her
      offspring. Numerous studies have been conducted in the Gulf Cooperation Council
      (GCC) countries to examine maternal and birth health. The objectives of this
      protocol for a systematic review are to systematically review and characterise
      the exposures and outcomes that have been examined in the mother and birth cohort
      studies in the GCC region, and to summarise the strength of association between
      key maternal exposures during pregnancy (ie, body mass index) and different
      health-related outcomes (ie, mode of birth delivery). The review will then
      synthesise and characterise the consequent health implications and will serve as
      a platform to help identify areas that are overlooked, point out limitations of
      studies and provide recommendations for future cohort studies. METHODS AND
      ANALYSIS: Medline, Embase, Cochrane Library and Web of Science electronic
      databases will be comprehensively searched. Two reviewers will independently
      screen each study for eligibility, and where discrepancies arise they will be
      discussed and resolved; otherwise a third reviewer will be consulted. The two
      reviewers will also independently extract data into a predefined Excel
      spreadsheet. The included studies will be categorised on the basis of whether the
      participant is a mother, infant or mother-infant dyad. Outcome variables will be
      divided along two distinctions: mother or infant. Exposure variables will be
      divided into six domains: psychosocial, biological, environmental,
      medical/medical services, maternal/reproductive and perinatal/child. Studies are
      expected to be of heterogeneous nature; therefore, quantitative syntheses might
      be limited. ETHICS AND DISSEMINATION: There is no primary data collection;
      therefore, ethical review is not necessary. The findings of this review will be
      disseminated in a peer-reviewed journal and presented at relevant conferences.
      PROSPERO REGISTRATION NUMBER: CRD42017068910.

PMID- 29374678
TI  - Multiple types of human papillomavirus infection and anal precancerous lesions in
      HIV-infected men in Taiwan: a cross-sectional study.
AB  - OBJECTIVES: This study aimed to assess the relationship between infection with
      multiple human papillomavirus (HPV) types and abnormal anal cytology in HIV
      infected men. DESIGN: An observational, cross-sectional study. SETTING: A
      regional referral hospital in Taiwan. PARTICIPANTS: In total, 714 HIV-infected
      men were enrolled between March 2011 and June 2016. Thin preparation anal Pap
      smears were interpreted according to the 2001 Bethesda System. Thirty-seven types
      of HPV were detected by reverse line blotting, including 13 oncogenic types and
      24 non-oncogenic types. OUTCOME MEASURES: The relationship between anal HPV
      infection and abnormal anal cytology in people of Asian ethnicity and the
      coverage efficacy in HPV-vaccinated HIV-infected men. RESULTS: On anal cytology,
      175 (24.5%) subjects had atypical squamous cells of undetermined significance
      (ASCUS) or higher grades of dysplasia, including 87 (49.7%) with ASCUS, 73
      (41.7%) with low-grade squamous intraepithelial lesions (LSILs) and 15 (8.6%)
      with high-grade squamous intraepithelial lesions (HSILs). A higher proportion of
      subjects with those without LSIL/HSIL (93.1% vs 67.3%, P<0.0001) had multiple HPV
      types. The odds of having LSIL/HSIL increased with an increasing number of HPV
      types: the ORs ranged from 1 for no HPV types to 6.96 (95% CI 2.38 to 20.37) for
      more than five types (Ptrend <0.0001). Multivariate logistic regression analysis
      showed a significant association between LSIL/HSIL and the number of HPV
      genotypes present (OR 1.20; 95% CI 1.02 to 1.42, P<0.05). HPV types covered by
      the nonavalent HPV vaccine (types 6/11/16/18/31/33/45/52/58) were detected in
      70.1% of the patients in this study. CONCLUSIONS: The odds of having anal
      LSIL/HSIL are approximately seventimes greater in HIV-infected men with than
      withoutsix or more types of HPV. Multiple HPV types in HIV-infected patients
      deserves aggressive follow-up, and HPV vaccination programme require scaling up.

PMID- 29374680
TI  - Correction: Electrosclerotherapy for capillary malformations: study protocol for
      a randomised within-patient controlled pilot trial.

PMID- 29374681
TI  - Stereotactic Body Radiation Therapy for Liver Tumors: Current Status and
      Perspectives.
AB  - Surgical resection is the standard therapy for solitary primary or metastatic
      liver tumors. However, liver tumors are often unresectable at diagnosis and
      hepatectomy is invasive. Local therapies, such as radiofrequency ablation, are
      used instead, which can be challenging. Recent advances in modern radiotherapy,
      including stereotactic body radiation therapy (SBRT), have increased the use of
      radiotherapy as a curative modality. SBRT delivers ablative high doses of
      irradiation in small volumes. SBRT for liver tumors provided local control with
      potential survival benefits in patients with inoperable status. However, the
      following issues remain: primary vs. metastatic liver cancers; SBRT-related
      toxicity and prevention; pathological features of liver cancers; and potential
      SBRT strategies. We summarized a literature review to summarize the effectiveness
      of SBRT and patient tolerance and present the current status and future
      perspective of SBRT for liver tumors. SBRT is a potential game changer for
      multimodal therapy.

PMID- 29374679
TI  - Randomised controlled trial of the sliding hip screw versus X-Bolt Dynamic Hip
      Plating System for the fixation of trochanteric fractures of the hip in adults: a
      protocol study for WHiTE 4 (WHiTE4).
AB  - INTRODUCTION: Sliding hip screw fixation is well established in the treatment of
      trochanteric fractures of the hip. The X-Bolt Dynamic Hip Plating System builds
      on the successful design features of the sliding hip screw but differs in the
      nature of the fixation in the femoral head. A randomised pilot study suggested
      that the X-bolt Dynamic Hip Plating System might provide similar health-related
      quality of life while reducing the risk of revision surgery when compared with
      the sliding hip screw. This is the protocol for a multicentre randomised trial of
      sliding hip screw versus X-Bolt Dynamic Hip Plating System for patients 60 years
      and over treated for a trochanteric fracture of the hip. METHODS AND ANALYSIS:
      Multicentre, multisurgeon, parallel, two-arm, randomised controlled trial.
      Patients aged 60 years and older with a trochanteric hip fracture are potentially
      eligible. Participants will be randomly allocated on a 1:1 basis to either
      sliding hip screw or X-Bolt Dynamic Hip Plating System. Otherwise, all care will
      be in accordance with National Institute for Health and Care Excellence guidance.
      A minimum of 1128 patients will be recruited to obtain 90% power to detect a
      0.075-point difference in EuroQol-5D health-related quality of life at 4 months
      postrandomisation. Secondary outcomes include mortality, residential status,
      revision surgery and radiographic measures. The treatment effect will be
      estimated using a two-sided t-test adjusted for age, gender and cognitive
      impairment based on an intention-to-treat analysis. ETHICS AND DISSEMINATION:
      National Research Ethics Committee approved this study on 5 February 2016
      (16/WM/0001). The study is sponsored by the University of Oxford and funded
      through an investigator initiated grant by X-Bolt Orthopaedics. A manuscript for
      a high-impact peer-reviewed journal will be prepared, and the results will be
      disseminated to patients through local mechanisms at participating centres. TRIAL
      REGISTRATION NUMBER: ISRCTN92825709.

PMID- 29374682
TI  - Neuroendocrine Neoplasms of the Appendix: A Review of the Literature.
AB  - Appendiceal neuroendocrine neoplasms (ANENs) comprise rare tumors of the
      appendix, mainly affecting young populations and characterized by a rather
      favorable prognosis. The aim of this review was to summarize the current
      knowledge on these neoplasms, focusing on the management and follow-up of such
      patients, which still remain under debate. ANENs account for 0.16-2.3% of
      appendectomies and are usually diagnosed incidentally. The histopathological
      diagnosis includes the immunohistochemical profile of the tumor in regard to
      synaptophysin and chromogranin A, as well as the Ki-67 index. The surgical
      management of ANENs is either simple appendectomy or a more extensive oncological
      operation including right hemicolectomy. This depends on the stage and the
      presence of risk factors suggesting a more aggressive disease, such as the exact
      location, mesoappendiceal or lymphovascular invasion, and the proliferative rate
      of the tumor. Despite their indolent course, ANENs may relapse. Therefore,
      lifetime observation is necessary for patients with tumors >2 cm and >1 cm plus
      additional risk factors; however, more studies should be conducted in order to
      determine the optimal follow-up strategy.

PMID- 29374683
TI  - Gastric Juice MicroRNAs as Potential Biomarkers for Screening Gastric Cancer: A
      Systematic Review.
AB  - BACKGROUND/AIM: To date, the combination of gastroscopy with biopsy remains the
      only test validated for screening gastric cancer (GC). Currently, analysis of
      circulating microRNAs (miRNAs or miRs) is providing interesting information on GC
      prognosis, but since these molecules are shared by several types of cancer, its
      clinical use could be questionable and difficult. MicroRNAs in gastric juice (GJ)
      could represent a cogent alternative to screening GC by biopsy. MATERIALS AND
      METHODS: We investigated the pertinent literature dealing with GC GJ microRNAs
      through four popular search engines (PubMed, Science Direct, Scopus and Google
      Scholar). RESULTS: As of 2017, only four studies had been published and were all
      from Chinese experience. MiR-421, miR-129, miR-21, miR-106a and miR-133a were the
      five molecules studied in the GJ of the enrolled patients. CONCLUSION: The GJ
      miRNA test is reliable and reproducible. The discussed GJ miRNAs appear to be new
      potential biomarkers for the screening of GC.

PMID- 29374684
TI  - Dual Role of Mitophagy in Cancer Drug Resistance.
AB  - The effectiveness of chemotherapy is largely limited by drug resistance. In the
      past few decades, modulation of anticancer drug resistance plays little role in
      benefit of clinical outcomes due to complex drug resistance mechanisms.
      Mitophagy, an important mitochondrial quality control system, selectively
      degrades excessive or damaged mitochondria by autophagy. Accumulating reports are
      suggesting that dysregulation of mitophagy contributes to neoplastic progression
      and drug resistance in various types of tumors. Mitophagy was originally thought
      to be an onco-suppressor that maintains cellular homeostasis and prevents
      oncogenic transformation. On the other hand, mitophagy promotes cancer cell
      survival under cytotoxic stress by degrading damaged mitochondria and reducing
      mitochondrial reactive oxygen species. Therefore, induction and inhibition of
      mitophagy in cancer drug resistance are controversial. In this review, we
      summarize current knowledge on the dual role of mitophagy in cancer drug
      resistance.

PMID- 29374685
TI  - Phosphaplatin Anti-tumor Effect Enhanced by Liposomes Partly via an Up-regulation
      of PEDF in Breast Cancer.
AB  - BACKGROUND/AIM: Phosphaplatin platinum (IV) (RRD4) complex has exceptional
      antitumor properties. The aim of this study was to investigate the effects and
      the mechanism of action of free and liposome-encapsulated RRD4 in breast cancer.
      MATERIALS AND METHODS: Liposome-encapsulated RRD4 prepared by thin-film
      dehydration: hydration and free RRD4 were tested in vivo and in vitro against 4T1
      breast cancer cells. Cell proliferation, migration and viability were determined.
      Tissue and cell production and expression of pigment epithelium-derived factor
      (PEDF) were assessed by ELISA and western blot. 4T1 cells treated with PEDF siRNA
      were evaluated for viability and apoptosis. RESULTS: RRD4 inhibited tumor growth
      and prevented distant metastasis. Liposome formulation enhanced this therapeutic
      benefit without increasing toxicity and prolonged RRD4 retention in tumor
      tissues. In vitro, RRD4 induced 4T1 apoptosis through up-regulation of FAS, BAX,
      and PUMA, and down-regulation of BCL2. RRD4 facilitates a FAS-intrinsic signaling
      mechanism. PEDF up-regulation represents another antitumor mechanism associated
      with this phosphaplatin compound. DISCUSSION: Free RRD4 or formulated into
      liposomes, are excellent candidates for adjuvant therapy against breast tumor
      growth and metastasis.

PMID- 29374686
TI  - Inhibition of Sirtuin 6 Induces Neuroblastoma Differentiation.
AB  - BACKGROUND/AIM: Sirtuins (SIRTs) play crucial roles in various signaling pathways
      that modulate differentiation and proliferation. We sought to elucidate the role
      of SIRTs in differentiation and proliferation of human neuroblastoma (NB).
      MATERIALS AND METHODS: NB cells were treated with nicotinamide (NAM), a non
      specific SIRT inhibitor, SIRT-targeted short hairpin RNAs, and retinoic acid to
      assess cell growth and differentiation. RESULTS: SIRTs are involved in
      proliferation and differentiation using NAM in BE(2)-C cells. Specifically, SIRT6
      knockdown in BE(2)-C cells reduced cell proliferation, induced neurite extension,
      corresponding with induction of p21CIP1 expression and G1 cell-cycle arrest.
      These effects were rescued by forced re-overexpression of SIRT6. SIRT6 expression
      was reduced in differentiated human NB sections, and RA-induced differentiation
      in BE(2)-C cells. CONCLUSION: SIRTs have important oncogenic properties in NB
      beyond its established functions in aging and genome stability. SIRT6 may
      represent a novel target for developing future therapeutics for the treatment of
      aggressive NBs.

PMID- 29374687
TI  - Natural Killer Cell Viability After Hyperthermia Alone or Combined with
      Radiotherapy with or without Cytokines.
AB  - BACKGROUND: The effects of hyperthermia and irradiation, alone and in
      combination, on natural killer (NK) cell viability were investigated in vitro.
      The roles of interleukin-2 (IL-2) and interferon (IFN) alpha, beta and gamma in
      rescuing NK cells from hyperthermia and irradiation were studied. MATERIALS AND
      METHODS: Non-selected NK cells were used as effector cells and K-562 cells as
      target cells. NK and K-562 cells were treated at 37 to 45 degrees C for 0 to 180
      min. The cells were irradiated at room temperature using single doses from 0 to
      60 Gy. Recombinant IL-2 at 100 to 450 U/ml and recombinant IFNalpha, beta and
      gamma at 1,000 U/ml were used for different periods of time. NK cell viability
      was measured by intracellular adenosine tri-, and diphosphate (ATP, ADP) levels
      via luminometer, trypan blue exclusion and propidium iodide (PI) staining.
      Binding capacity of NK effector cells to target K-562 cells was also
      microscopically assessed. RESULTS: Thermal treatments between 37 and 41 degrees C
      did not significantly affect the ATP levels of NK cells. Between 41 degrees C and
      42 degrees C, ATP levels significantly decreased, whilst there was an
      insignificant reduction up to 45 degrees C. At 42 degrees C or higher, no
      recovery was detectable. At 42 degrees C, the ATP level of NK cells rescued by IL
      2 were significantly higher than those of controls at 37 degrees C. IFNalpha,
      beta and gamma had no significant effects. A combination of heating at 42 degrees
      C and irradiation at 20 Gy significantly reduced the ATP levels (p<0.001) more
      than heating and irradiation alone. At 42 degrees C, IL-2 abolished the reduction
      of ATP levels by heating and irradiation. This effect was dependent on heating
      time and irradiation dose. The ATP/ADP ratio did not significantly change when NK
      cells were heated for different times at 42 degrees C. Thermal treatment of
      target K-562 cells at temperatures from 37 to 45 degrees C reduced the number of
      NK cells binding K-652 cells. CONCLUSION: In vitro, NK cell viability was
      strongly reduced between 41 degrees C and 42 degrees C. At 42 degrees C, the
      combination of irradiation and thermal treatment reduced the ATP levels in NK
      cells. However, IL-2 restored cell viability depending on thermal and radiation
      doses.

PMID- 29374689
TI  - Improved In Vivo Subcutaneous Tumor Generation by Cancer Cell Sheet
      Transplantation.
AB  - BACKGROUND/AIM: In vivo subcutaneous tumor models are generally prepared by the
      injection of a cancer cell suspension to evaluate the pharmaceutical effects on
      tumor tissues. However, dispersed cells show low biological activities because of
      enzyme-induced cell harvest treatment, thus limiting the formation of tumor
      tissues. In this study, a biologically active cancer cell monolayer (cell sheet)
      was used to improve the efficiency of subcutaneous tumor formation. MATERIALS AND
      METHODS: Mouse lung squamous cancer cells (KLN-205) were transplanted on the
      subcutis of immunocompetent and immunodeficient mice in the form of a dispersed
      cell suspension or cell sheet, and the tumor formation abilities were
      independently investigated with considering immunological effects. RESULTS: Mouse
      lung squamous cancer cells (KLN-205) scarcely formed malignant tumors on the
      mouse subcutis following injection of the cell suspension. On the other hand,
      cell transplantation in the cell sheet form successfully achieved effective tumor
      development due to only weak immunological reactions at the transplanted area.
      And thus, the cancer cells maintained their proliferative activity to form
      tumors. CONCLUSION: Transplantation of the cell sheet is effective to generate
      subcutaneous tumor-bearing mice, providing a useful alternative to the low tumor
      formation activities induced with the conventional injection method.

PMID- 29374688
TI  - Fluorescence-guided Surgery with Splenic Preservation Prevents Tumor Recurrence
      in an Orthotopic Nude-mouse Model of Human Pancreatic Cancer.
AB  - AIM: The purpose of this study was to investigate whether splenectomy influences
      tumor recurrence after fluorescence-guided surgery (FGS) in an orthotopic nude
      mouse model of pancreatic cancer. MATERIALS AND METHODS: Green fluorescence
      protein (GFP)-labeled human pancreatic cancer cells (MiaPaCa2-GFP) were
      subcutaneously injected into the flanks of nude mice. Subcutaneous tumors were
      harvested and surgical orthotopic implantation (SOI) was performed in the tail of
      the pancreas with small tumor fragments. FGS was performed 21 days after SOI.
      Mice were then randomly divided into FGS-only control group (n=7) and FGS plus
      splenectomy group (n=8). Tumor recurrence was analyzed by laparotomy 21 days
      after FGS. RESULTS: In the control group, no recurrence was found. In contrast,
      multiple peritoneal seeded nodules were observed in two mice of the splenectomy
      group (0% vs. 25%, p=0.467). CONCLUSION: Postoperative tumor recurrence only
      occurred in the splenectomy-treated group suggesting that FGS can spare the
      patient the morbidity of splenectomy.

PMID- 29374690
TI  - MicroRNA Expression in KRAS- and BRAF-mutated Colorectal Cancers.
AB  - BACKGROUND/AIM: KRAS and BRAF are two genes commonly mutated in colorectal cancer
      (CRC). Even though BRAF is a downstream target of KRAS in the MAPK signalling
      pathway, KRAS- and BRAF-mutated CRCs are found to display several different
      clinical and histopathological features. We investigated whether a differential
      expression of microRNAs (miRNAs) could explain the clinicopathological
      differences seen between KRAS- and BRAF-mutated CRCs. MATERIALS AND METHODS:
      Using a PCR array, we analyzed the expression of 84 different miRNAs in CRC cell
      lines wild-type in KRAS and BRAF, or mutated in KRAS or BRAF. RESULTS: Ten miRNAs
      were selected for further analyses in tumor tissue specimens (let-7a, let-7i, miR
      10a, miR-10b, miR-31, miR-100, miR-181a, miR-181b, miR-372, and miR-373). BRAF
      mutated tumors were found to express significantly higher levels of miR-31 as
      well as significantly lower levels of miR-373, compared to wild-type tumors.
      CONCLUSION: Our results suggest that KRAS- and BRAF-mutated CRCs may have
      different miRNA signatures compared to CRC tumors wild-type in KRAS and BRAF.
      However, no difference in expression levels between KRAS- and BRAF-mutated tumors
      was evident for the miRNAs analyzed in this study.

PMID- 29374691
TI  - Exploratory Radiomics in Computed Tomography Perfusion of Prostate Cancer.
AB  - BACKGROUND/AIM: An evaluation if radiomic features of CT perfusion (CTP) can
      predict tumor grade and aggressiveness in prostate cancer was performed.
      MATERIALS AND METHODS: Forty-seven patients had biopsy-confirmed prostate cancer,
      and received a CTP. Blood volume (BV), blood flow (BF) and mean transit time
      (MTT) maps were derived and 1,701 radiomic features were determined per patient.
      Regression models were built to estimate post-surgical Gleason score (GS),
      microvessel density (MVD) and distinguish between the different risk groups.
      RESULTS: Six out of the 47 patients had to be excluded from further analysis. A
      weak relationship between postsurgical GS and one radiomic parameter was found
      (R2=0.21, p=0.01). The same parameter combined with MTT inter-quartile range was
      prognostic for the risk group categorisation (AUC=0.81). Two different radiomic
      parameters were able to distinguish between low-intermediate risk and high
      intermediate risk (AUC=0.77). Four parameters correlated with MVD (R2=0.53,
      p<0.02). CONCLUSION: This exploratory study shows the potential of radiomics to
      classify prostate cancer.

PMID- 29374692
TI  - Down-regulation of B-Cell Translocation Gene 1 by Promoter Methylation in
      Colorectal Carcinoma.
AB  - BACKGROUND: B-cell translocation gene 1 (BTG1) acts as a tumour suppressor in
      human malignancies. However, the precise mechanism of BTG1 down-regulation in
      colorectal carcinoma (CRC) remains unclear. We analyzed BTG1 expression in CRC
      cell lines and tissues and investigated the mechanism underlying the observed
      alterations. MATERIALS AND METHODS: Real-time polymerase chain reaction (PCR) and
      western blot analyses were performed to analyze BTG1 expression in CRC cell
      lines. The methylation status of the BTG1 promoter region in cell lines was
      determined by methylation-specific PCR, and the effect of demethylation on BTG1
      expression was explored with 5-aza-deoxycytidine treatment. BTG1 protein
      expression in CRC tissue samples was evaluated using immunostaining. RESULTS: CRC
      cell lines and tissue samples expressed lower levels of BTG1 compared to
      controls, and BTG1 levels were significantly lower in metastatic than primary
      CRC. In BTG1-down-regulated CRC cell lines, the BTG1 promoter was highly
      methylated, and 5-aza-deoxycytidine significantly restored BTG1 expression.
      CONCLUSION: BTG1 down-regulation in CRC occurs through epigenetic repression,
      which is involved in the development and progression of CRC.

PMID- 29374693
TI  - Association of eIF4E and SPARC Expression with Lymphangiogenesis and Lymph Node
      Metastasis in Hypopharyngeal Cancer.
AB  - BACKGROUND/AIM: Head and neck squamous cell carcinomas (HNSCC) are characterized
      by aggressiveness, early recurrence and lymph node metastasis. Therefore, there
      is an urgent need to identify new biomarkers and drug targets. MATERIALS AND
      METHODS: Neck dissection specimens from 11 patients diagnosed with hypopharyngeal
      cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel
      endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of
      eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and
      rich in cysteine (SPARC) using immunoblot analysis. RESULTS: Compared to lymph
      node biopsies of healthy controIs, LVD was significantly increased in metastatic
      lymph nodes as well as in advanced primary tumors. Overexpression of eIF4E and
      SPARC was demonstrated in all hypopharyngeal cancer specimens. Notably, we
      observed that increased LVD significantly correlated with the expression of eIF4E
      as well as SPARC levels. CONCLUSION: eIF4E- and SPARC-associated signaling
      pathways may be associated with lymphangiogenesis and could be exploited to
      counteract the spread of hypopharyngeal cancer cells.

PMID- 29374694
TI  - Does the Use of Hair Dyes Increase the Risk of Developing Breast Cancer? A Meta
      analysis and Review of the Literature.
AB  - BACKGROUND/AIM: Hair dye may contain mutagenic compounds which could be
      associated with an increased incidence of breast cancer in women who use it. The
      aim of this study was to examine the association between the personal use of hair
      dyes and the risk of breast cancer. MATERIALS AND METHODS: We conducted a
      literature review of epidemiological studies reporting breast cancer-specific
      risks among hair dye users versus non-users. The data for the incidence of breast
      cancer following the 'ever' use of hair dye in studies which met the inclusion
      criteria was analysed using a meta-analysis. The relative risk ratio (RR) and 95%
      confidence intervals (CI) were determined. RESULTS: A total of eight case-control
      studies published between 1980 and 2017 met the selection criteria and were
      included in the meta-analysis. Compared to non-users, using a random effects
      model and the Duval and Tweedie's trim and fill procedure to adjust for
      publication bias in the presence of between studies heterogeneity, the adjusted
      RR for women using hair dyes was 1.1885 (95% CI=1.03228-1.36835). This indicates
      an 18.8% increased risk of future development of breast cancer among hair dye
      users. CONCLUSION: Although further work is required to confirm our results and
      clarify potential mechanisms, our findings suggest that exposure to hair dyes may
      contribute to an increased breast cancer risk.

PMID- 29374695
TI  - Low Expression of CD44 Is an Independent Factor of Poor Prognosis in Ovarian
      Mucinous Carcinoma.
AB  - AIM: To determine whether CD44, which is associated with tumor growth and
      metastasis, is related to carcinogenesis and prognosis in ovarian mucinous
      carcinomas (MACs). MATERIALS AND METHODS: Tissue blocks from 71 patients with
      benign mucinous ovarian tumors were used in the study: 35 were from patients with
      borderline mucinous ovarian tumors, and 60 from patients with MACs.
      Immunochemical analysis was performed to evaluate the expression of CD44 and
      examine its association with tumorigenesis and survival. RESULTS: Compared to
      benign tumors, borderline tumors had high CD44 expression levels (p=0.047).
      Conversely, MACs had lower expression than borderline tumors (p=0.032).
      Progression-free and overall survival of patients with MAC with low CD44
      expression were worse than those of patients with high expression (p=0.04 and
      p=0.02, respectively). CONCLUSION: Malignant transformation of mucinous tumors is
      associated with changes in CD44 expression, with low expression level being a
      prognostic factor in MAC.

PMID- 29374696
TI  - SATB1 Level Correlates with Ki-67 Expression and Is a Positive Prognostic Factor
      in Non-small Cell Lung Carcinoma.
AB  - BACKGROUND: Non-small cell lung carcinomas (NSCLCs), mainly adenocarcinoma (AC)
      and squamous cell carcinoma (LSCC), account for about 80% of all lung cancer
      cases. One of the proteins involved in NSCLC progression may be special AT-rich
      binding protein 1 (SATB1), a potent transcriptional regulator, able to control
      the expression of whole sets of genes simultaneously. SATB1 has been found to be
      associated with aggressive phenotype and poor prognosis in numerous malignancies,
      including breast, colon, ovary and prostate cancer. However, its role in NSCLC is
      still not fully understood. The aim of this study was to investigate the
      expression of SATB1 protein and mRNA in NSCLC and non-malignant lung tissue
      (NMLT) samples, as well as to determine possible relationships of SATB1
      expression with both the expression of Ki-67 and the clinicopathological data of
      the patients. MATERIALS AND METHODS: The study was performed on 277 NSCLC (158
      AC, 119 LSCC) and 20 NMLT samples. RESULTS: We observed increased SATB1
      immunoreactivity in NSCLC when compared to NMLT, and in LSCC when compared to AC
      cases. We also noted that an elevated SATB1 immunoreactivity was associated with
      a poor degree of AC differentiation, whereas in LSCC, an inverse relationship was
      observed. Our analyses revealed that the expression of SATB1 positively
      correlated with Ki-67 index in NSCLC and LSCC, but not in AC cases. Finally, we
      found that high SATB1 expression was associated with a better overall survival of
      patients with NSCLC. CONCLUSION: SATB1 plays diverse roles in different NSCLC
      subtypes, and its expression may have a prognostic significance for patients with
      these tumours.

PMID- 29374697
TI  - Effective Timing of Surgical Resection of Colorectal Cancer Liver Metastases
      During Chemotherapy.
AB  - BACKGROUND/AIM: The aim of the present study was to further develop our previous
      study on c-Met expression in colorectal cancer and epithelial-mesenchymal
      transition (EMT) induced by hepatocyte growth factor (HGF), to investigate EMT in
      the process of liver metastases, and evaluate the effects of chemotherapy on EMT
      cells as a therapeutic strategy for colorectal liver metastasis. MATERIALS AND
      METHODS: CT26 colon cancer cells were treated with 5-FU and oxaliplatin with or
      without HGF. The signaling pathway was evaluated by western blotting analysis,
      and drug resistance was evaluated by the MTT (3-(4,5-dimethyl-2-tetrazolyl)-2,5
      diphenyl-2H tetrazolium bromide) assay. RESULTS: Under pretreatment with HGF for
      96 h, 5 MUM and 10 MUM of 5-FU mediated significant growth inhibition by 72.5+/
      3.9% and 76.2+/-2.4%, respectively, compared to HGF alone, and by 105.1+/-2.8%
      and 103.5+/-2.9%, respectively, without HGF. The expression of E2F1 was decreased
      significantly to 50.5+/-3.8% after 24 hours by HGF with a reduction of both
      cyclin D1 to 52.1+/-7.0% and E to 73.7+/-3.8%. Thymidylate synthase was also
      decreased in a time-dependent manner to 80.6+/-2.0% after 24 h and to 52.7+/-1.5%
      after 96 h. CONCLUSION: The presence of HGF was found to increase the 5-FU
      induced death signal, JNK pathway, and inhibition of cell growth. As its
      mechanism, HGF was shown to decrease E2F-1 by reducing cyclin D or E by cell
      cycle activation, resulting in inactivation of thymidylate synthase. The
      chemotherapeutic effect of 5-FU was increased in HGF- but not TGF-beta-induced
      EMT.

PMID- 29374698
TI  - Acetaminophen and Metamizole Induce Apoptosis in HT 29 and SW 480 Colon Carcinoma
      Cell Lines In Vitro.
AB  - BACKGROUND/AIM: The perioperative phase is supposed to be a period with high
      vulnerability for cancer dissemination. Acetaminophen and metamizole are common
      analgesics administered during this phase. We investigated the effect of
      acetaminophen, metamizole and 4-methylaminoantipyrine (MAA) on proliferation and
      apoptosis of colon carcinoma cell lines (SW 480 and HT 29). MATERIALS AND
      METHODS: Proliferation was detected by cell proliferation ELISA BrdU, and
      apoptosis by Annexin V staining. Cytochrome c and caspase 3, 8 and 9 expression
      levels were detected by western blot. RESULTS: Acetaminophen, metamizole or MAA
      caused slight changes in proliferation. Acetaminophen, metamizole or the
      combination increased apoptosis in both cell lines. All agents decreased caspase
      3 and 8 expression in SW480. Acetaminophen decreased caspase 9 expression in both
      cell lines. CONCLUSION: In clinically relevant doses, acetaminophen and/or
      metamizole induce apoptosis in both colon cancer cell lines. Both mitochondrial
      and death receptor pathways might be involved in acetaminophen-induced apoptosis.

PMID- 29374699
TI  - Prognostic Significance of NSCLC and Response to EGFR-TKIs of EGFR-Mutated NSCLC
      Based on PD-L1 Expression.
AB  - BACKGROUND/AIM: Recent clinical trials have shown that immune checkpoint
      blockades that target either PD-1 or PD-L1 yield remarkable responses in a
      subgroup of patients with non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: We retrospectively examined, by immunohistochemical analysis, 211 NSCLC
      samples. Using 32 independent samples, we also evaluated PD-L1 expression in
      NSCLC patients with EGFR gene mutations treated by EGFR-TKIs. RESULTS: Overall
      survival of PD-L1-positive stages I-III NSCLC and stage I NSCLC and stages I-III
      squamous cell carcinoma (SQ) were significantly shorter than those of PD-L1
      negative NSCLC (p<0.01 and p=0.02 and p=0.01, respectively). In stage I NSCLC and
      stages I-III SQ, PD-L1 expression was found to be independent predictor of death
      after multivariate analysis. Response to EGFR-TKIs was not significantly
      different between PD-L1-positive and PD-L1-negative NSCLC patients with EGFR
      mutations. CONCLUSION: PD-L1 expression was a significant independent predictor
      of poor outcome in NSCLC patients.

PMID- 29374700
TI  - Quantitative Structure-Cytotoxicity Relationship of 2-Azolylchromones.
AB  - BACKGROUND/AIM: Twenty-four 2-azolylchromones were subjected to quantitative
      structure-activity relationship (QSAR) analysis based on their cytotoxicity and
      tumor specificity, in order to find their new biological activities. MATERIALS
      AND METHODS: Cytotoxicity against two human oral squamous cell carcinoma cell
      lines and two human normal oral mesenchymal cells was determined by the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor specificity
      (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50)
      against oral cells to that against oral squamous cell carcinoma cell lines.
      Potency-selectivity expression (PSE) value was calculated by dividing the TS
      value by CC50 against tumor cells. Apoptosis markers were detected by western
      blot analysis. Physicochemical, structural and quantum-chemical parameters were
      calculated based on the conformations optimized by force-field minimization.
      RESULTS: Three sets of 4H-1-benzopyran-4-ones with indole ring showed much higher
      TS values than those with pyrrole, pyrazole, imidazole, 1,2,4-triazole, 1,2,3
      triazole, indazole and benzimidazole rings. Among those with an indole ring, the
      compound having a 6-methoxy group, that exhibited the highest cytotoxicity,
      yielded one to three-order higher PSE values to compared with other groups of
      compounds. Western blot analysis demonstrated that this compound stimulated the
      cleavage of caspase-3, suggesting the induction of apoptosis. QSAR analysis
      demonstrated that TS values were correlated with 3D shape, polarizability,
      ionization potential and lipophilicity. CONCLUSION: Chemical modification of the
      lead compound may be a potential choice for designing a new type of anticancer
      drug.

PMID- 29374701
TI  - HMGA1 and MMP-11 Are Overexpressed in Human Non-melanoma Skin Cancer.
AB  - BACKGROUND/AIM: The High-Mobility Group A1 (HMGA1) protein has been implicated in
      human malignancies, playing an important role in cancer proliferation,
      angiogenesis and metastasis. Increased HMGA1 expression has been found in skin
      mouse tumors, whereas Hmga1-null mice were protected against skin carcinogenesis.
      Here, we examined the expression of HMGA1 in human skin tumors, squamous cell
      carcinoma and basal cell carcinoma. MATERIALS AND METHODS: Tumor and normal skin
      tissues from 15 affected patients were surgically excised, and mRNA and protein
      extraction was performed. mRNA and protein content for both HMGA1 and MMP-11, a
      proteinase enzyme that plays a role in tumor development and progression, was
      measured by real-time PCR and western blotting, respectively. Data were analyzed
      by the SPSS software. RESULTS: HMGA1 mRNA and protein expression patterns were
      higher in neoplastic skin lesions, compared to normal skin (p<0.001). Similar
      results were observed for MMP-11. CONCLUSION: Our data confirm previous
      observations in mice studies, and suggest that HMGA1 and MMP-11 may play a key
      role in the proliferation and progression of skin tumors in humans.

PMID- 29374702
TI  - Intense Pulsed Light: Friend or Foe? Molecular Evidence to Clarify Doubts.
AB  - BACKGROUND/AIM: Intense pulsed light (IPL) has been extensively applied in the
      field of dermatology and aesthetics; however, the long-term consequences of its
      use are poorly unknown, and to the best of our knowledge there is no study on the
      effect of IPL in neoplastic lesions. In order to better understand the molecular
      mechanisms underlying IPL application in the skin, we used an animal model of
      carcinogenesis obtained by chemical induction with 12-dimethylbenz(a)anthracene
      (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). MATERIALS AND METHODS:
      Institute of Cancer Research (ICR) mice were administered DMBA and/or TPA and
      treated with IPL. Skin was evaluated by histopathology and 2DE-blot-MS/MS
      analysis. RESULTS: Our data evidenced an inflammatory response and a metabolic
      remodeling of skin towards a glycolytic phenotype after chronic exposure to IPL,
      which was accomplished by increased oxidative stress and susceptibility to
      apoptosis. These alterations induced by IPL were more notorious in the DMBA
      sensitized skin. Keratins and metabolic proteins seem to be the more susceptible
      to oxidative modifications that might result in loss of function, contributing
      for the histological changes observed in treated skin. CONCLUSION: Data highlight
      the deleterious impact of IPL on skin phenotype, which justifies the need for
      more experimental studies in order to increase our understanding of the IPL long
      term safety.

PMID- 29374704
TI  - PDGFRalpha/HER2 and PDGFRalpha/p53 Co-expression in Oral Squamous Cell Carcinoma.
AB  - AIM: The purpose of this study was to explore the parallel expression of platelet
      derived growth factor receptor alpha (PDGFRalpha) and human epidermal growth
      factor receptor 2 (HER2) or p53 in relation to clinicopathological parameters of
      oral squamous cell carcinoma (OSCC) to define their role in progressive growth of
      tumor. MATERIALS AND METHODS: Expression of PDGFRalpha, HER2 and p53 was
      evaluated in 71 OSCC samples by immunohistochemistry. HER2 status was verified by
      fluorescence in situ hybridization. RESULTS: PDGFRalpha and p53 expression were
      associated with tumor grade (p=0.043 and p=0.040, respectively). HER2 expression
      was more frequent in advanced (III/IV) cancer (p=0.006). A positive correlation
      of PDGFRalpha with HER2 (r=0.267; p=0.024) and with p53 (r=0.266; p=0.025) was
      noted. PDGFRalpha/HER2 and PDGFRalpha/p53 co-expression was found more often in
      G3 than in G1 and G2 tumors (p=0.008 and p=0.015, respectively). CONCLUSION: Our
      study revealed that PDGFRalpha/HER2 and PDGFRalpha/p53 co-expression exists in
      poorly differentiated OSCCs, suggesting that cooperation between these proteins
      might enhance aggressive behavior of tumor.

PMID- 29374703
TI  - Transglutaminase 2 Regulates Self-renewal and Stem Cell Marker of Human
      Colorectal Cancer Stem Cells.
AB  - BACKGROUND/AIM: The aim of this study was to investigate the role of
      transglutaminase 2 (TGM2) in colorectal cancer stem cells (CCSCs). MATERIALS AND
      METHODS: We used the TU12 cell line possessing CD133-expressing CCSCs. After
      isolating CD133 (-) and CD133 (+) CCSCs, we overexpressed and knocked-down TGM2
      to investigate its role in human CCSCs. RESULTS: The expression level of TGM2 was
      25-fold higher in tumorigenic cells than non-tumorigenic cells. We found that
      knockdown of TGM2 by specific RNA interference markedly inhibited cell growth and
      caused down-regulation of the stemness markers, CD133, SOX2, and beta-catenin. We
      further demonstrated that knockdown of TGM2 inhibited cell metastatic abilities
      by down-regulating N-cadherin and vimentin and up-regulating E-cadherin. These
      findings revealed that TGM2 expression is markedly increased in human colorectal
      cancer and that down-regulation of TGM2 in tumors may serve as a treatment for
      colorectal cancer patients. Therefore, this study indicate that TGM2 affects the
      metastatic potential and stemness of CCSCs by regulating EMT- and stemness
      related proteins. CONCLUSION: The metastatic potential of CSCs arises from highly
      expressed TGM2.

PMID- 29374705
TI  - Autophagy Induced by Naftopidil Inhibits Apoptosis of Human Gastric Cancer Cells.
AB  - AIM: Naftopidil is used to treat benign prostate hyperplasia. Moreover, previous
      studies have shown that naftopidil reduced viability of many types of cancer
      cells. Therefore, we investigated the antitumor mechanism of naftopidil in this
      study. MATERIALS AND METHODS: We used the HGC27 human gastric cancer cell line.
      It was treated with naftopidil, pan-caspase inhibitor, and chloroquine
      diphosphate (CQ). Cell viability and cell death were investigated by the assay
      and annexin V/ propidium iodide assay. Phosphorylation of protein kinase B (AKT)
      (Ser473) was measured by western blotting. Alteration of light chain 3B (LC3B)
      was investigated by western blotting and immunofluorescence. RESULTS: Naftopidil
      reduced phospho-AKT (Ser473) and altered LC3B. Combination of naftopidil and CQ
      reduced cell viability and phospho-AKT (Ser 473). CONCLUSION: Naftopidil induces
      apoptosis and autophagy of HGC27 cells, however, autophagy is considered to
      inhibit apoptosis. We concluded naftopidil and CQ have a synergistic antitumor
      effect.

PMID- 29374706
TI  - The Mesenchymal-Epithelial and Epithelial-Mesenchymal Cellular Plasticity of
      Liver Metastases with Digestive Origin.
AB  - BACKGROUND: Few data are available regarding the epithelial to mesenchymal
      transition (EMT) /mesenchymal to epitheilal transition (MET) in the liver
      metastasis of digestive cancers. The aim of this study was to establish EMT/MET
      metastatic tumor cell plasticity according to the histological growth pattern of
      liver metastases. MATERIALS AND METHODS: Biopsies from 25 patients with liver
      metastasis (desmoplastic, replacement and pushing type) were evaluated. Double
      immunostaining of E-cadherin/vimentin, keratin 8,18/vimentin and E-cadherin/
      keratin 8,18 were performed. RESULTS: The following cell types were noted:
      epithelial, mesenchymal, non-differentiated and differentiated hybrid
      mesenchymal/ epithelial and non-hybrid phenotype. All cases had mesenchymal/
      epithelial phenotype cells. A significant correlation was found between the non
      differentiated hybrid mesenchymal/ epithelial phenotype metastatic cells and
      histological growth pattern for gastric and colorectal cancer. CONCLUSION: A MET
      targeting strategy, in conjunction with conventional chemotherapy, may be useful
      for the treatment of liver metastases.

PMID- 29374707
TI  - Quantitative Structure-Cytotoxicity Relationship of Cinnamic Acid Phenetyl
      Esters.
AB  - BACKGROUND/AIM: Many phenolic acid phenethyl esters possess diverse biological
      effects including antioxidant, cytoprotective, anti-inflammation and anti-tumor
      activities. However, most previous antitumor studies have not considered the
      cytotoxicity against normal cells. Ten cinnamic acid phenetyl esters were
      subjected to quantitative structure-activity relationship (QSAR) analysis, based
      on their cytotoxicity and tumor-specificity, in order to find their new
      biological activities. MATERIALS AND METHODS: Cytotoxicity against four human
      oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells
      was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the
      mean 50% cytotoxic concentration (CC50) against normal oral cells to that against
      human oral squamous cell carcinoma cell lines. Potency-selectivity expression
      (PSE) value was calculated by dividing the TS value by CC50 against tumor cells.
      Apoptosis markers were detected by western blot analysis. Physicochemical,
      structural and quantum-chemical parameters were calculated based on the
      conformations optimized by force-field minimization. RESULTS: Western blot
      analysis demonstrated that [9] stimulated the cleavage of caspase-3, suggesting
      the induction of apoptosis. QSAR analysis demonstrated that TS values were
      correlated with shape, size and ionization potential. CONCLUSION: Chemical
      modification of the lead compound may be a potential choice for designing a new
      type of anticancer drugs.

PMID- 29374708
TI  - Loading Efficiency of Polymersomes with Contrast Agents and their Intracellular
      Delivery: Quantum Dots Versus Organic Dyes.
AB  - BACKGROUND/AIM: Contrast nanocarriers as drug-delivery systems, capable of
      selective delivery to cancer cells and solid tumors, are essential for the
      development of new diagnostic and therapeutic (theranostic) strategies. The
      present study aimed to investigate the loading efficiency of chitosan-based
      polymersomes with fluorescent contrast substances [quantum dots (QDs) and
      conventional organic dyes] and the possibility to control their release from the
      polymer matrix into cells by chemical modifications and electroporation.
      MATERIALS AND METHODS: All investigated fluorophores were retained within the
      polymer globule via electrostatic and hydrophilic-hydrophobic interactions,
      without conjugation with the polymer. The fluorophore-loaded polymersomes were
      characterized by dynamic light scattering, zeta-potential titration, and
      fluorescence spectroscopy. The release of fluorophore from the polymersomes,
      passively or after electroporation, was detected by 5-step spin-ultrafiltration,
      combined with fluorescence spectroscopy of the upper phase (supernatant) of the
      filter unit. Passive intracellular delivery of the nanoparticles to HeLa cells
      was detected by fluorescence confocal microscopy. RESULTS: The QDs were retained
      tightly and continuously in the polymer matrix, while the organic fluorophores
      [fluorescein isothiocyanate (FITC), FITC-dextran10,000 and FITC-dextran70,000]
      were released rapidly from the polymersomes. The detergent Brij significantly
      increased the retention of FITC-dextran10,000 in the polymer globule.
      Electroporation up to 1000 V/cm did not induce release of QDs from the
      polymersomes, but accelerated the release of Brij-treated FITC-dextran10,000 B
      from the polymer matrix. High-voltage pulses (over 750 V/cm) induced also
      fragmentation or aggregation of the nanoparticles. QD_labeled polymersomes
      penetrated passively in cancer cells after 24-hour incubation. CONCLUSION: The
      results suggest that QD-labeled polymersomes are appropriate fluorescent probes
      and a nano-drug delivery system with high tracing opportunities for in vitro and
      in vivo applications. Furthermore, loading polymersomes with organic dyes with
      different molecular weights (such as FITC-dextrans) is a simple model for
      visualizing and predicting the rate of release of small organic molecules (e.g.
      conventional drugs, other contrasts, stabilizers, and supplements) from the
      polymer matrix.

PMID- 29374709
TI  - Non-invasive Detection of Bladder Tumors Through Volatile Organic Compounds: A
      Pilot Study with an Electronic Nose.
AB  - BACKGROUND/AIM: Cystoscopy, the standard diagnostic for bladder tumors, is
      uncomfortable, invasive, and expensive. The available urine-based marker systems
      all lack accuracy. Measuring volatile organic compounds (VOCs) from urine is a
      promising alternative. This pilot study evaluates the feasibility of
      discriminating bladder cancer patients' urine from healthy controls with an
      electronic nose. MATERIALS AND METHODS: Headspace measurements of urine samples
      of 30 patients with confirmed transitional cell carcinoma (TCC) and 30 healthy
      controls were performed with Cyranose 320 calculating Mahalanobis distance and
      linear discriminant analysis. Histology reports following TUR-BT were correlated
      with urine findings. RESULTS: After storage at -20 degrees C, Cyranose correctly
      detected 28/30 already confirmed TCC samples and 26/30 healthy controls (p<0.01),
      sensitivity 93.3%, specificity 86.7%. Storage at -80 degrees C led to similar
      results: 28/30 tumor samples and 28/30 control samples were correctly allocated;
      sensitivity and specificity both 93.3%. CONCLUSION: VOC detection is a promising
      tool to detect bladder tumors. Further research will test against possible
      confounders like bacteriuria.

PMID- 29374710
TI  - Decreased Expression of SATB2 Associates with Tumor Growth and Predicts Worse
      Outcome in Patients with Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND/AIM: SATB2 (special AT-rich sequence-binding protein 2) is a DNA
      binding protein that is involved in transcriptional regulation and chromatin
      remodeling. SATB2 protein has been described as a promising novel marker in
      several human cancers. PATIENTS AND METHODS: This study compared SATB2 expression
      in tumor and matched unchanged renal tissues collected from 57 patients with
      clear cell renal cell carcinoma (ccRCC). SATB2 mRNA levels were determined by
      quantitative polymerase chain reaction, while SATB2 protein expression was
      estimated by immunohistochemistry. Moreover, the associations between SATB2
      expression in ccRCC samples and clinicopathological and survival data of the
      patients were investigated. RESULTS: The mRNA level of SATB2 was lower in tumor
      tissues than in samples of corresponding unchanged kidney. Although the average
      immunoreactivity of SATB2 protein did not differ significantly between cancer
      cells and epithelial cells of proximal convoluted tubules, the decreased SATB2
      expression in tumor specimens inversely correlated with the size of primary tumor
      and predicted worse patients' outcome. CONCLUSION: The results of the presented
      study suggest the tumor-suppressing function of SATB2 and that the expression
      level of this protein can be considered a potential prognostic factor in ccRCC.

PMID- 29374711
TI  - Ursolic Acid Causes Cell Death in PC-12 Cells by Inducing Apoptosis and Impairing
      Autophagy.
AB  - Ursolic acid (UA) is a natural pentacyclic triterpene that has various biological
      activities, including anticancer and anti-inflammatory effects. This study
      investigated the ability of UA to cause cell death in pheochromocytoma (PC-12)
      cells. UA was cytotoxic to PC-12 cells (half-maximum inhibitory
      concentration=53.2 MUM) and significantly reduced the clonogenic ability of PC-12
      cells. It also triggered apoptosis by reducing the level of B-cell lymphoma 2
      (BCL2), activating caspase-3, and inducing cleavage of poly (ADP-ribosyl)
      polymerase. To investigate the effects of UA treatment on the induction and
      progression of autophagy, the levels of p62 and the conversion of the microtubule
      associated protein light chain 3 (LC3)-I to LC3-II, which are important markers
      of autophagic flux, were monitored. UA treatment induced the accumulation of p62
      and increased the LC3-II/LC3-I ratio. These results demonstrate that UA treatment
      induced autophagy, but the downstream signaling pathway was blocked. In summary,
      this study shows that UA kills PC-12 cells by inducing apoptosis and impairing
      autophagy progression.

PMID- 29374712
TI  - Antitumor Effect of Burchellin Derivatives Against Neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is one of the most commonly encountered malignant solid
      tumors in the pediatric age group. We examined the antitumor effects of five
      burchellin derivatives against human neuroblastoma cell lines. MATERIALS AND
      METHODS: We evaluated cytotoxicity by the MTT assay for four human neuroblastoma
      and two normal cell lines. We also performed analysis of the apoptotic induction
      effect by flow cytometry, and examined the expression levels of apoptosis- and
      cell growth-related proteins by western blot analysis. RESULTS: We found that one
      of the burchellin derivatives (compound 4) exerted cytotoxicity against the
      neuroblastoma cell lines. Compound 4 induced caspase-dependent apoptosis via a
      mitochondrial pathway. The apoptosis mechanisms induced by compound 4 involved
      caspase-3, -7 and -9 activation and poly (ADP-ribose) polymerase cleavage. In
      addition, compound 4 induced cell death through inhibition of the cell growth
      pathway (via extracellular signal-regulated kinase 1 and 2, AKT8 virus oncogene
      cellular homolog, and signal transducer and activator of transcription 3).
      CONCLUSION: Compound 4 exerted cellular cytotoxicity against neuroblastoma cells
      via induction of caspase-dependent apoptosis, and may offer promise for further
      development as a useful drug for the treatment of advanced neuroblastoma.

PMID- 29374713
TI  - Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory
      Prostate Cancer Cells.
AB  - BACKGROUND/AIM: Androgen deprivation therapy remains the principal treatment for
      patients with advanced prostate cancer, though, most patients will eventually
      develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated
      maspin-induction has been identified in cancer patients. However, the role of
      maspin on the anticancer activity of curcumin derived from turmeric (Curcuma
      longa) in HRPC cells has not been elucidated. MATERIALS AND METHODS: The
      anticancer action of curcumin in hormone-independent prostate cancer cells
      (DU145, and PC-3) was determined by measures of cell survival rate. The cause of
      maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was
      evaluated by measures of cell survival rate, cell-cycle distribution, and
      apoptosis signaling analysis. RESULTS: Our present study showed that PC-3 cells
      (with higher maspin expression) were more sensitive than DU145 cells to curcumin
      treatment (with lower maspin expression). RNA interference-mediated maspin
      silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced
      apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed
      lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with
      control cells. CONCLUSION: Maspin can enhance the sensitivity of HRPC cells to
      curcumin treatment.

PMID- 29374714
TI  - Survival in Limited Disease Small Cell Lung Cancer According to N3 Lymph Node
      Involvement.
AB  - BACKGROUND/AIM: There are several definitions of limited disease (LD) in small
      cell lung cancer (SCLC), differing with respect to N3 disease accepted. We
      analyzed patients from a randomized trial comparing two schedules of thoracic
      radiotherapy (TRT) in LD SCLC to investigate whether there were survival
      differences between N3 subcategories (n=144). PATIENTS AND METHODS: Patients with
      a baseline CT scan available were analysed. Patients received four courses of
      cisplatin/etoposide and TRT of 45 Gy/30 fractions (twice daily) or 42 Gy/15
      fractions (once daily). RESULTS: Median overall survival (OS) was 23.3 months in
      the whole cohort. N3-patients (n=37) had shorter survival than those with N0-2
      (16.7 vs. 33.0 months; p<0.001). There were no significant OS-differences between
      the N3 subcategories, but patients with metastases to two or more N3 regions had
      shorter survival than other N3 patients (13.4 vs. 19.9 months; p=0.011).
      CONCLUSION: There were no survival differences between the N3 subcategories,
      suggesting that all N3 disease should be considered as LD.

PMID- 29374715
TI  - Control of Nausea and Vomiting in Patients Receiving
      Anthracycline/Cyclophosphamide Chemotherapy for Breast Cancer.
AB  - BACKGROUND/AIM: Chemotherapy-induced nausea and vomiting (CINV) is one of most
      distressing adverse events during cancer chemotherapy. In breast cancer patients
      receiving anthracycline and cyclophosphamide (AC) chemotherapy, CINV is poorly
      controlled. PATIENTS AND METHODS: The prevalence of guideline-consistent
      antiemetic medication and control of CINV were investigated retrospectively in
      breast cancer patients receiving the first cycle of AC chemotherapy. Risks for
      CINV were analyzed by the multivariate logistic regression analysis. The effect
      of olanzapine added to the standard antiemetic medication on the incidence of
      CINV was subsequently evaluated in separate patients who received the first cycle
      of AC chemotherapy. RESULTS: Although the guideline-consistent antiemetic
      medication was performed in all subjects, the control rate of nausea (32%), but
      not vomiting (78%) was low. Risk analysis indicated that age younger than 55-year
      old was a significant factor that reduces the control of both nausea and
      vomiting. Olanzapine (5 mg/day for 5 days), when added to the standard three-drug
      antiemetic medication, significantly improved the control of nausea and complete
      response. CONCLUSION: CINV was poorly controlled in breast cancer patients
      receiving AC chemotherapy, in which age younger than 55-year-old was a
      significant risk for both nausea and vomiting. Olanzapine was effective for
      improvement of the control of CINV associated with AC chemotherapy. Therefore,
      care should be taken to prevent CINV in young patients receiving AC chemotherapy
      by adding olanzapine to the standard three-drug antiemetic medication.

PMID- 29374716
TI  - A Phase I Study of Hypofractionated Carbon-ion Radiotherapy for Stage III Non
      small Cell Lung Cancer.
AB  - BACKGROUND/AIM: The aim of this study was to assess the feasibility and safety of
      hypofractionated carbon-ion radiotherapy (C-ion RT) in patients with stage III
      non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with
      untreated, histologically proven, unresectable stage III NSCLC and not candidates
      for chemotherapy were included in this study. C-ion RT was planned and
      administered with 4 Gy (relative biological effectiveness (RBE)) in daily
      fractions for a total dose of 64 Gy (RBE) without combined chemotherapy. Dose
      limiting toxicity (DLT) was defined as suspension of C-ion RT treatment for 2
      weeks due to >= grade 2 pneumonitis, or any other >= grade 3 adverse event, or as
      any >= grade 4 adverse event within 3 months from the start of treatment.
      RESULTS: Six patients were treated between June 2013 and December 2014. The
      planned full dose of C-ion RT (64 Gy (RBE)) was completed in all patients. No
      patient developed DLT, and no patient experienced toxicities of >=grade 3
      severity. The overall response rate was 100%, and local tumor control was
      achieved in all patients during the survival period. CONCLUSION: Hypofractionated
      C-ion RT of patients with stage III NSCLC was feasible and well tolerated.
      Although the number of patients in this study was small, the results support
      further investigations to confirm the long-term therapeutic efficacy of this
      treatment.

PMID- 29374717
TI  - Effect of Neoadjuvant Chemoradiotherapy on Lymph Node Micrometastases in Thoracic
      Esophageal Cancer.
AB  - AIM: The purpose of this study was to clarify the effect of neoadjuvant
      chemoradiotherapy (nCRT) on lymph node micrometastasis (LNM) in esophageal
      squamous cell carcinoma (ESCC). PATIENTS AND METHODS: The therapeutic efficacy of
      nCRT was analyzed in 41 ESCC patients randomized to the Surgery group (n=21) and
      the nCRT group (n=20). Lymph node specimens from patients were classified into
      two categories, micrometastasis (MM) and tumor cell microinvolvement (MI), after
      immunohistochemical evaluation. RESULTS: The incidence rates of patients
      presenting MM with or without MI or MI alone in the Surgery group were
      significantly higher than those in the nCRT group. The 10-year survival rate of
      15 patients with simultaneous histological metastasis (HM) and LNM was
      significantly lower than that in the 26 patients without LNM. Within the nCRT
      group, the 10-year survival rates of patients with versus those without HM were
      not significantly different; however, the 10-year survival rate of the 5 patients
      with simultaneous HM and LNM was significantly lower than that of the 15 patients
      without LNM. CONCLUSION: ESCC patients with LNM may benefit from nCRT, and
      evaluation of the simultaneous presence of HM and LNM may facilitate accurate
      prediction of survival in ESCC patients.

PMID- 29374718
TI  - Does Patient-reported Dyspnea Reflect Thoracic Disease Characteristics in
      Patients with Incurable Cancer?
AB  - BACKGROUND/AIM: A considerable proportion of patients with incurable cancer
      experience dyspnea. This study evaluates associations between the feeling of
      dyspnea, as quantified by radiotherapy patients scoring their symptoms before
      palliative treatment with the Edmonton symptom assessment system (ESAS), and
      potential underlying causes. PATIENTS AND METHODS: Retrospective comparison of
      the incidence of different parameters that could cause a feeling of dyspnea in
      two groups, patients with no or minimal dyspnea (ESAS score 0-2) and those with
      dyspnea scores >2. RESULTS: The mean dyspnea score of all 102 patients was 2.6.
      Dyspnea scores >2 were present in 68% of patients with lung cancer, 50% of those
      with breast cancer, 39% of those with prostate cancer and 26% of those with other
      tumors (p=0.025). Dyspnea scores >2 were also present in 69% of patients with
      pleural effusion (vs. 40% in patients without pleural effusion), p=0.031. Among
      patients treated with palliative thoracic radiotherapy, 71% had dyspnea scores >2
      (40% if other targets were irradiated), p=0.041. In 13% of patients, anemia and
      pulmonary comorbidity were the most likely explanation for dyspnea. In 29% the
      feeling of dyspnea could not be related to objective findings. CONCLUSION: In the
      majority of patients, the feeling of dyspnea was associated with the presence of
      thoracic metastases with or without pleural effusion from extrathoracic primary
      tumors or with a lung cancer diagnosis. A substantial proportion of patients
      reported dyspnea that could be related neither to cancer burden nor comorbidity.

PMID- 29374719
TI  - Phase II Study of S-1 plus Trastuzumab for HER2-positive Metastatic Breast Cancer
      (GBCCSG-01).
AB  - AIM: Treatment strategies for patients with human epidermal growth factor 2
      (HER2)-positive metastatic breast cancer (MBC) have significantly progressed. The
      use of trastuzumab, a monoclonal antibody targeting the HER2 (human epidermal
      growth factor 2) protein, in combination with chemotherapy improves survival in
      patients with HER2-positive breast cancer. S-1, an oral combination of
      fluorouracil derivatives, is widely used in Japan and is more convenient than
      intravenous drugs. However, little is known about the combination of S-1 and
      trastuzumab in patients with HER2-positive MBC. PATIENTS AND METHODS: We
      conducted a single-arm, open-label, multicenter prospective phase II study to
      evaluate the efficacy of an S-1 plus trastuzumab regimen for HER2-positive MBC. S
      1 was administered orally [80-120 mg, based on body surface area (BSA)] twice a
      day for 14 consecutive days in a 3-week cycle. Patients with BSA of <1.25 m2
      received a total of 80 mg of S-1, those with BSA >=1.5 m2 received 120 mg, and
      the remaining received 100 mg daily in two divided doses. Trastuzumab was
      administered intravenously at 8 mg/kg on day 1 of the first cycle and at 6 mg/kg
      on day 1 of subsequent cycles, i.e., every 3 weeks. RESULTS: Between December
      2008 and March 2013, 10 patients were enrolled and received a median of 17
      (range=3-76) cycles of treatment. Overall response and clinical benefit rates
      were 60.0% and 90.0%, respectively. Progression-free survival was 15.8 (95%
      confidence interval=9.4-29.6) months and overall survival was 45.5 (95%
      confidence interval=37.1-62.2) months. Grade 3/4 adverse events included were
      neutropenia and hyperglycemia in one patient each (10.0%). There was no
      clinically significant cardiotoxicity. CONCLUSION: The combination of S-1 and
      trastuzumab was tolerable and had excellent efficacy with good response and
      disease control in this study. S-1 plus anti-HER2 therapy is a feasible treatment
      option for HER2-positive MBC.

PMID- 29374720
TI  - Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing
      Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil.
AB  - BACKGROUND/AIM: The purpose of this study was to identify adverse prognostic
      factors for patients with advanced esophageal cancer undergoing chemotherapy with
      docetaxel, cisplatin and 5-fluorouracil (DCF). PATIENTS AND METHODS: The study
      cohort comprised of 45 patients with advanced esophageal cancer who underwent
      induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment
      outcomes and factors affecting early recurrence and death were analyzed. RESULTS:
      Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%.
      Clinically evident lymph node metastasis and clinical stage were associated with
      recurrence within 1 year and death within 2 years. Low maximum standardized
      uptake value (SUVmax) after induction DCF therapy and small decreases in SUVmax
      from pre- to post-DCF therapy were also predictors of recurrence and poor
      prognosis. CONCLUSION: Induction DCF therapy may be ineffective for advanced
      stage esophageal cancer and clinical lymph node metastasis (>=N2, >=stage IIIB).
      Moreover, small decreases in SUVmax DCF therapy are associated with early disease
      relapse and death.

PMID- 29374721
TI  - Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.
AB  - BACKGROUND: In ulcerative colitis (UC), the majority of colorectal carcinomas
      (CRC) arise in the vast colorectal mucosal domain built with mucus-producing
      goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny,
      spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the
      four reported cases of colonic carcinoma developing in GALT mucosa in UC,
      searching for possible precursor lesions connected with the evolution of these
      tumours. MATERIALS AND METHODS: The clinical history, age, gender, endoscopic
      descriptions, and the pathology (localization, gross and histological
      descriptions of the luminal surface) of the four UC-GALT carcinomas reported in
      the literature were reviewed. RESULTS: The luminal surface in three out of the
      four carcinomas revealed conventional (tubular/villous) adenomas or high-grade
      dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0).
      CONCLUSION: GALT carcinomas do occur, albeit infrequently, in patients with UC.
      The finding that three out of the four GALT carcinomas on record were covered by
      conventional adenomas or by high-grade dysplasia strongly suggests that non
      invasive conventional neoplasias might often precede GALT carcinomas in UC.

PMID- 29374722
TI  - Surgical Outcomes and Morbidity After Radical Surgery for Ovarian Cancer in
      Aberdeen Royal Infirmary, the Northeast of Scotland Gynaecologic Oncology Centre.
AB  - BACKGROUND/AIM: Ovarian cancer (OC) has a high mortality rate and usually
      presents late in advanced stage, which poses challenges to management. Better
      understanding of the disease biology and application of radical surgery (RS) to
      achieve no visible residual tumor, alongside with chemotherapy, may lead to
      longer survival amongst these patients. Our purpose was to examine the
      demographic characteristics, surgical morbidity and outcomes of patients
      undergoing RS for OC. MATERIALS AND METHODS: A retrospective cohort study of
      women undertaking surgery for OC between February 2014 and September 2016 in
      Aberdeen Royal Infirmary. RESULTS: A total of 121 women had surgery for OC of
      whom 78 (64.5%) were stage II and above. Of these, 40 (51.3%) women had primary
      and 38 (48.7%) had interval debulking surgery with 42 (53.8%) having radical
      surgery. The most common procedures that were performed as part of RS included
      rectosigmoid resection (n=20, 47.6%), small bowel resection (n=10, 23.8%),
      splenectomy (n=9, 21.4%). Morbidity outcomes included blood loss >1.5 lt. (n=14,
      33.3%), hospitalization >7days (n=31, 73.8%), sepsis (n=8, 19%). There was no
      short-term mortality. Debulking outcomes were: no macroscopic residual disease
      (n=36, 85.7%), <=10 mm disease (n=2, 4.8%), and >=10 mm disease (n=3, 7.1%).
      CONCLUSION: Our findings support the practise where RS for OC can be offered to
      selected patients, with good surgery outcomes and low morbidity rates.

PMID- 29374723
TI  - Low-dose Pressurized Intrathoracic Aerosol Chemotherapy (PITAC) as an Alternative
      Therapy for Pleuropulmonary Involvement in Pseudomyxoma Peritonei.
AB  - BACKGROUND/AIM: Pseudomyxoma peritonei (PMP) is a rare disease characterized by
      mucinous ascites and widespread peritoneal implants. It usually originates from
      the rupture of an adenoma/adenocarcinoma of the appendix. Although this tumor is
      only superficially invasive and does not metastasize, it could be a fatal
      disease. Extra-abdominal spread of PMP is an unusual occurrence with few reports
      in medical literature. CASE REPORT: A 50-year-old man was diagnosed with PMP
      according to the findings of thorax and abdomen CT scan and cytologic and
      histological examinations. The radiological exam showed irregular thickening on
      the surface of left diaphragmatic and parietal pleura. RESULTS: First,
      cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy
      (HIPEC) for the abdominal disease was performed. Histopathological examination
      confirmed the diagnosis of low grade PMP. The radiological evaluation performed 5
      months later showed a dimensional increase in pleural nodules. The treatment
      consisted of an extensive intrathoracic cytoreductive surgery in combination with
      pressurized intra-thoracic aerosol chemotherapy (PITAC). Postoperative course was
      uneventful. CONCLUSION: PMP with pleural extension is a rare phenomenon and
      carries an unfavourable prognosis. Due to the rarity of this presentation, its
      correct treatment is still unclear. We present a therapeutic approach to be
      applied in selected patients.

PMID- 29374724
TI  - Association of Preoperative Nutritional Status with Prognosis in Patients with
      Esophageal Cancer Undergoing Salvage Esophagectomy.
AB  - BACKGROUND: To investigate whether malnutrition is associated with poor prognosis
      of patients who undergo salvage esophagectomy. We examined the association
      between the preoperative prognostic nutritional index (PNI) and prognosis of
      patients who undergo salvage esophagectomy. PATIENTS AND METHODS: We conducted a
      single-center retrospective study and reviewed hospital patient records for tumor
      characteristics and patient outcomes. Univariate and multivariate survival
      analyses were carried out using the Cox proportional hazards regression model.
      RESULTS: Thirty-two patients with esophageal squamous cell carcinoma (ESCC) who
      underwent salvage esophagectomy between 1998 and 2015 at our Institute were
      included in this study. Univariate analysis revealed that clinical response
      (p=0.045), preoperative PNI (p<0.001), pT (p=0.024), pN (p=0.004), and residual
      tumors (p<0.001) were significant prognostic factor for overall survival.
      Multivariate analysis using age and these five variables found no independent
      prognostic factors. Multivariate analysis using three preoperative variables
      (age, clinical response, and preoperative PNI) revealed that PNI was an
      independent prognostic preoperative factor for overall survival (p=0.005).
      CONCLUSION: Preoperative nutritional status is associated with the prognosis of
      patients undergoing salvage esophagectomy.

PMID- 29374725
TI  - High STMN1 Expression Is Associated with Tumor Differentiation and Metastasis in
      Clinical Patients with Pancreatic Cancer.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer
      related deaths worldwide. Stathmin 1 (STMN1) suppression was reported to reduce
      cellular viability and migration potential. However, no previous studies have
      addressed whether STMN1 overexpression is associated with malignant potential in
      PDAC. MATERIALS AND METHODS: To clarify the clinical significance of STMN1 in
      PDAC, the STMN1 expression in 104 PDAC samples was evaluated by
      immunohistochemistry. Moreover, we evaluated the proliferative potential and
      migration ability of pancreatic cancer cell line Suit2 cells highly expressing
      STMN1. RESULTS: Cytoplasmic STMN1 were higher levels in PDAC than in
      corresponding non-cancerous tissues. PDAC patients with high STMN1 (n=29) were
      significantly associated with poor differentiation and distant metastasis
      compared to those with low STMN1 (n=75). The proliferation rates and migration
      ability in Suit2-STMN1 were higher than those of Suit2-mock. CONCLUSION: STMN1
      evaluation could be a useful progression marker, and STMN1 may be a promising
      candidate for targeted therapies in PDAC.

PMID- 29374726
TI  - Clinical Assessment of Micro-residual Tumors during Stereotactic Body Radiation
      Therapy for Hepatocellular Carcinoma.
AB  - BACKGROUND: This study aimed to assess the need to consider microscopic invasion
      in terms of treatment planning in stereotactic body radiation therapy (SBRT) for
      hepatocellular carcinoma and elucidate the appropriate clinical target volume
      (CTV) margin. PATIENTS AND METHODS: A total of 121 patients (with 146 liver
      tumors) who underwent SBRT between July 2007 and August 2016 were analyzed,
      regarding overall survival and local control (LC). RESULTS: The 2- and 5-year LC
      rates were 91.5% and 89.8%, respectively. Planning target volume (PTV) margin <8
      mm was associated with poor LC. Of the 77 patients with PTV margin of <8 mm, age
      <75 years was associated with poor LC, while alpha-fetoprotein (AFP) <=20 ng/ml
      was associated with good LC. CONCLUSION: In patients with high AFP levels, there
      is a possibility of microscopic invasion around the tumor, suggesting that LC may
      be improved by adding an additional clinical target volume margin to the gross
      tumor volume.

PMID- 29374727
TI  - The Prognostic Implications of Bone Invasion in Gingival Squamous Cell Carcinoma.
AB  - BACKGROUND/AIM: This study evaluated the associations between bone invasion of
      gingival squamous cell carcinoma (SCC) and clinicopathological manifestations,
      and aimed to determine whether bone invasion is an independent prognostic factor
      in gingival SCC. PATIENTS AND METHODS: The study was a retrospective review of 78
      patients with gingival SCC who underwent surgery with curative intent. The level
      of bone invasion was pathologically categorized as medullary, cortical or no bone
      invasion. RESULTS: Cortical and medullary bone invasion was present in 29 and 22
      patients, respectively. There was a significant association between medullary
      bone invasion and tumor size (p=0.017), pathological N classification (p<0.001),
      differentiation (p=0.017) and lymphovascular invasion (p=0.007). Medullary bone
      invasion and lymphovascular invasion were independent predictors of reduced
      overall survival (p=0.015, 0.048); medullary bone invasion was also an
      independent predictor of reduced disease-specific survival (p=0.018). CONCLUSION:
      Pathologically-proven medullary bone invasion and lymphovascular invasion were
      found to be key prognostic factors in gingival SCC. The results suggest that it
      is necessary to consider adjuvant therapy in patients with medullary bone
      invasion.

PMID- 29374728
TI  - Comparison of Laparoscopic and Open Surgery for Colorectal Cancer in Patients
      with Severe Comorbidities.
AB  - BACKGROUND/AIM: To evaluate the safety of laparoscopic colorectal cancer surgery
      for patients with severe comorbidities. PATIENTS AND METHODS: A total of 203
      consecutive patients with severe comorbidities who underwent resection for
      colorectal cancer were retrospectively divided into laparoscopic and open primary
      resection groups. An age-adjusted Charlson comorbidity index >=6 was considered
      as severe comorbidity. RESULTS: Blood loss (31 g vs. 207 g, p<0.01) and total
      postoperative complications (10.0% vs. 27.5%, p<0.01) in the laparoscopic group
      were significantly decreased compared to the open group. Incidence of
      postoperative ileus (0.0% vs. 7.2%, p=0.06) and length of postoperative hospital
      stay (11 days vs. 14 days, p=0.08) in the laparoscopic group were improved,
      though not significantly, compared to the open group. CONCLUSION: Laparoscopic
      resection for patients with severe comorbidities is safe, and is associated with
      a lower rate of overall operative complications compared to open surgery.

PMID- 29374729
TI  - Image Quality Assessment of 2D versus 3D T2WI and Evaluation of Ultra-high b
      Value (b=2,000 mm/s2) DWI for Response Assessment in Rectal Cancer.
AB  - AIM: The purpose of this IRB-approved, retrospective study was to compare image
      quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance
      imaging (MRI) sequences and to investigate the additional value of ultra-high b
      value diffusion-weighted imaging (DWI; b=2,000 mm/s2) for both rectal cancer
      staging and evaluating treatment response. MATERIALS AND METHODS: From 12
      February to 24 August 2016, 26 consecutive patients (22 males, four females; mean
      age: 61.9+/-14.0 years) with histologically-proven rectal cancer. In total 31
      examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The
      patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen,
      Germany). Three radiologists (3, 4, and 5 years of experience in MRI,
      respectively) independently assessed all images and rated the image quality of
      DWI (b=800 mm/s2), apparent diffusion coefficient map, DWI (b=2,000 mm/s2), 3D
      sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each
      patient, respectively. In addition, signal intensity ratios (SIR) were calculated
      between rectal cancer and obturator internus muscle (background) in all patients
      after CRT on DWI (b=2,000 mm/s2) and correlated with histopathological regression
      grade (RG). RESULTS: Tumor delineation was significantly better by 2D T2WI than
      3D T2WI both before and after CRT (before CRT: Z=-3.2, p=0.02; after CRT: Z=
      4.408, p<0.001; all: Z=-5.192; p<0.001) and was the preferred method, although
      image quality ratings were not significantly different (3D sagittal: 4.00+/-0.48;
      2D sagittal: 4.03+/-0.34, p=0.713; 3D axial: 3.85+/-0.61, 2D axial: 3.78+/-0.64,
      p=0.537). Independent t-test showed significantly higher SIR between those with
      RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good
      response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete
      response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort.
      In two patients, tumor was invisible on b2000 following CRT (RG 3 and 4,
      respectively). Interobserver agreement was mostly good (kappa>=0.6) regarding
      image quality assessment, except for poor agreement (kappa=0.4) in DWI (b2000)
      between the two less-experienced readers. CONCLUSION: In conclusion, 3D T2WI
      might be useful for evaluating response to neoadjuvant therapy in a
      comprehensive, cost-effective protocol, where 2D imaging seems to be preferable.
      In addition, DWI (b2000) may be beneficial in assessing both the primary and the
      residual tumor after CRT in rectal cancer and SIR may be helpful in assessing
      response to CRT.

PMID- 29374730
TI  - Two-step Intensity-modulated Radiation Therapy for Oropharyngeal Cancer: Initial
      Clinical Experience and Validation of Clinical Staging.
AB  - AIM: To evaluate the clinical results of two-step intensity-modulated radiation
      therapy (IMRT) for oropharyngeal cancer. PATIENTS AND METHODS: Eighty patients
      were treated with two-step IMRT between 2002 and 2014. Whole-neck radiotherapy
      (44.0-50.0 Gy/22-25 fractions) was delivered by IMRT, followed by boost IMRT to
      the high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Forty
      seven patients received concurrent chemotherapy. Immunohistochemistry for human
      papillomavirus type 16 (HPV/p16) was performed for 64 patients. RESULTS: The 5
      year overall survival and locoregional control rates for stage I, II, III, and
      IVA-B disease were 80.0%, 75.0%, 78.0%, and 64.0% and 100.0%, 75.0%, 92.0%, and
      82.0%, respectively. Overall survival was significantly higher in HPV/p16
      positive patients than in HPV/p16-negative patients (p=0.01). Xerostomia of grade
      2 or more was noted in 10 patients. CONCLUSION: Favourable overall survival and
      locoregional control rates with excellent salivary preservation were obtained
      using the two-step IMRT method for oropharyngeal cancer.

PMID- 29374731
TI  - Preoperative Platelet to Albumin Ratio Predicts Outcome of Patients with
      Cholangiocarcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate the prognostic index of the
      preoperative platelet to albumin ratio (PAR) in patients who underwent primary
      resection for cholangiocarcinoma. PATIENTS AND METHODS: A total of 59 patients
      were divided into two groups: those with PAR >=72.6*103 or <72.6*103 according to
      the area under the receiver operating characteristics curve. RESULTS: PAR was
      significantly inversely associated with overall (OS) and disease-free (DFS)
      survival on univariate analysis. PAR showed significance on multivariate analysis
      for OS (hazard ratio=6.232, 95% confidence interval=1.283-30.279, p=0.023), along
      with tumor differentiation (p=0.009), nodal involvement (p=0.001), intraoperative
      blood loss (p=0.001), and serum carcinoembryonic antigen (CEA) (p=0.012). High
      PAR was also significantly associated poor DFS on multivariate analysis (hazard
      ratio(HR)=4.422, 95% confidence interval(CI)=1.168-16.732, p=0.029), along with
      tumor differentiation (p=0.009). CONCLUSION: PAR is a useful prognostic index for
      OS and DFS in patients with cholangiocarcinoma after primary resection. By
      accumulating cases prospectively, this new index may be a reference for use
      before neoadjuvant chemotherapy.

PMID- 29374732
TI  - Protrusion on the Depressed Surface of Non-polypoid T1 Colorectal Cancer Is
      Associated with Venous Invasion.
AB  - AIM: The treatment strategies for T1 colorectal cancer (CRC) include both
      surgical and endoscopic resection. Surgical resection is indicated if
      lymphovascular invasion is present; however, the endoscopic prediction of
      lymphovascular invasion has not been reported. We aimed to correlate endoscopic
      morphology with pathological findings, including lymphovascular invasion, in non
      polypoid T1 CRC. MATERIALS AND METHODS: We retrospectively investigated 63
      patients with non-polypoid T1 CRC surgically resected between 2008 and 2016. Four
      typical endoscopic findings related to deep submucosal invasion, namely
      protrusion from a depressed surface, fold convergence, fullness and hardness,
      were assessed to elucidate their association with pathological findings. RESULTS:
      Protrusion was the only finding significantly correlated with positive venous
      invasion (67.9% of the lesions with protrusion vs. 34.3% of those without
      protrusion, p=0.01), which was also confirmed by a multivariable analysis (odds
      ratio(OR)=3.72, 95% confidence interval(CI)=1.24-11.2, p=0.02). CONCLUSION: The
      endoscopic finding of protrusion on a depressed surface may be a sign indicating
      venous invasion in non-polypoid T1 CRC.

PMID- 29374733
TI  - Patients with Increased Levels of the Oxidative Stress Biomarker SOD1 Appear to
      Have Diminished Postoperative Pain After Midline Laparotomy: A Randomised Trial
      with Special Reference to Postoperative Pain Score (NRS).
AB  - BACKGROUND/AIM: The levels of the oxidative stress biomarker superoxide dismutase
      (SOD1) in plasma in relation to pain at rest 24 hours after (NRS24) midline
      laparotomy in patients with rectus sheath block (RSB) analgesia is unknown.
      PATIENTS AND METHODS: Initially, 56 patients (39 with cancer), each with an
      intravenous oxycodone pump as patient-controlled analgesia, were randomized to
      four groups: control group, no RSB (n=12), single-dose (n=16), repeated-dose
      (n=12) and continuous infusion (n=16) of RSB analgesia. The plasma levels of SOD1
      were measured directly before, immediately after and 24 hours after surgery. Pain
      at rest was scored on an 11-point numeric rating scale 24 hours postoperatively
      (NRS24: 0=no pain to 10=worst pain). RESULTS: The median plasma level of SOD1
      increased immediately after operation and this was statistically highly
      significant (p=0.007). The median plasma level of SOD1 then decreased 24 hours
      postoperatively and this postoperative decrease was also statistically highly
      significant (p<0.001). The median plasma levels of SOD1 did not differ
      significantly between patients with benign disease and those with cancer,
      preoperatively and after surgery. There was highly significant positive
      correlation between SOD1 and glutathione peroxidase (GPX1) values postoperatively
      (r=0.67, p<0.001) and a trend for an inverse correlation between the individual
      values of the NRS24 and plasma SOD1 values postoperatively in patients with
      benign disease and those with cancer (r=-0.30, p=0.09). CONCLUSION: Midline
      laparotomy significantly alters the level of oxidative stress marker SOD1
      immediately after surgery, but the level normalizes 24 hours following surgery.
      Interestingly, patients with increased levels of SOD1 appeared to have diminished
      postoperative pain after midline laparotomy.

PMID- 29374734
TI  - Comparison of Two Radiotherapy Regimens for Metastatic Spinal Cord Compression:
      Subgroup Analyses from a Randomized Trial.
AB  - BACKGROUND/AIM: According to our randomized trial, 5*4Gy was comparable to 10*3Gy
      for metastatic spinal cord compression. Since it remained unclear whether
      findings applied to poor and intermediate prognoses patients, subgroup analyses
      were performed. PATIENTS AND METHODS: In patients with poor prognoses, 58
      received 5*4Gy, 53 received 10*3Gy. In intermediate-prognoses patients, numbers
      were 43 and 49. RESULTS: In patients with poor prognoses, 1-month overall
      response (OR) was 85% after 5*4Gy and 10*3Gy (p=0.99), improvement 38% vs. 42%,
      ambulatory status 60% vs. 64% (p=0.83), 6-month local progression-free survival
      (LPFS) 75% vs. 69% (p=0.74) and 6-month overall survival (OS) 26% vs. 19%
      (p=0.43). In patients with intermediate prognoses, 1-month OR was 89% after 5*4Gy
      and 93% after 10*3Gy (p=0.85), improvement 39% vs. 45%, ambulatory status 84% vs.
      82% (p=0.90), 6-month LPFS 79% vs. 92% (p=0.17) and 6-months OS 65% vs. 58%
      (p=0.65). CONCLUSION: 5*4Gy was not significantly inferior to 10x3Gy in both
      subgroups.

PMID- 29374735
TI  - Effects of Neoadjuvant 5-Fluorouracil and Cisplatin Therapy in Patients with
      Clinical Stage II/III Esophageal Squamous Cell Carcinoma.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) with 5-fluorouracil and cisplatin (FP)
      has been administered to patients with clinical stage II or III esophageal
      squamous cell carcinoma (ESCC). We aimed to confirm the clinical efficacy and
      outcomes of NAC with FP. PATIENTS AND METHODS: The clinicopathological features
      and survival of 152 patients with clinical stage II/III ESCC who received NAC
      with FP followed by radical esophagectomy were analyzed. RESULTS: The R1/2
      resection rate was higher (p=0.06) and the high histological response rate was
      significantly lower (p=0.05) in those with clinical stage III disease. Invasion
      depth significantly improved in those with less than cT3 (17/30. 57%), but did
      not in more invasive cases (35/122, 29%) (p=0.004). T Factor was frequently
      improved in those with clinical stage II (p=0.08). Five-year survival rates in
      clinical stage II and III were 73% and 41%, respectively. A multivariate analysis
      identified clinical stage (p=0.01) and residual tumor (p<0.01) as independent
      prognostic factors. CONCLUSION: NAC with FP is effective for patients with
      clinical stage II ESCC, while its potency may be lower for those with clinical
      stage III or cT3 disease.

PMID- 29374736
TI  - Efficacy and Safety of Drug Eluting Bead TACE with Microspheres <150 MUm for the
      Treatment of Hepatocellular Carcinoma.
AB  - BACKGROUND/AIM: To retrospectively evaluate the efficacy and safety of drug
      eluting bead (DEB) transarterial chemoembolisation (TACE) with microspheres <150
      MUm for the treatment of hepatocellular carcinoma (HCC) with respect to overall
      survival, progression-free survival, tumor response and the peri-interventional
      toxicity. MATERIALS AND METHODS: In this retrospective, single-center study we
      analyzed 32 HCC-patients (BCLC A: 10 patients, BCLC B: 17 patients, BCLC C: 5
      patients), who were treated with (DEB) <15 MUm (DCBeadM1(r)) loaded with
      epirubicin between 2011 and 2015. We analyzed MRI and CT-scans as well as blood
      results like AFP, bilirubin and liver enzymes before (t0) and after (t1=first
      follow-up, t2=last follow-up within 6 months) locoregional treatment. The tumor
      response was evaluated by MRI and CT considering m-RECIST and the EASL-criteria
      as well as alpha-fetoprotein (AFP) levels in the peripheral blood. RESULTS: We
      found a significant tumor response at all follow-up times (p<0.05) according to m
      RECIST criteria and a significant tumor response between t0 vs. t1 (p<0.05) and
      t0 vs. t2 (p<0.05) according to EASL criteria. We observed a significant decrease
      of the AFP-level between t0 and t1. The objective response rates (ORR) of target
      lesions were 64.3% and 78.5 % corresponding to m-RECIST and EASL, respectively.
      The median overall survival (OS) was 30.5 months, the progression-free survival
      in relation to the target lesion was 14.3 months by using m-RECIST and EASL
      criteria. In the period of 30 days after treatment we found no grade 5 adverse
      events (AE). During the follow-up period 1 abscess (3.7%) was observed. In a
      total of 5 patients, 4 (14.7%) biliomas with no need of treatment and 3 (10.7%)
      widening of the intrahepatic bile ducts were noted. CONCLUSION: The use of DEB
      <150 MUm (DCBeadM1(r)) shows promising results in the treatment of HCC without
      showing substantial hepatic toxicity, but some widening of the intrahepatic bile
      ducts and one abscess. Further trials are necessary to evaluate the efficacy and
      toxicity of DEB-TACE with M1(r)-beads.

PMID- 29374737
TI  - Radiation Therapy for Patients with Bone Metastasis from Uterine Cervical Cancer:
      Its Role and Optimal Radiation Regimen for Palliative Care.
AB  - AIM: To determine the role of radiation therapy for patients with bone metastasis
      from uterine cervical cancer and identify an optimal radiation regimen. PATIENTS
      AND METHODS: A total of 20 patients with bone metastases from uterine cervical
      cancer received radiation therapy to the pelvis. The median total dose of 60.2 Gy
      in the 2 Gy per fraction-equivalent dose (EQD2) was delivered to cervical tumors
      of all patients. Thirteen patients underwent chemotherapy during and/or following
      radiation therapy. RESULTS: In 18 of 20 patients, the primary tumors disappeared
      or were markedly reduced after radiation therapy. In all but one of 17 patients
      with pelvic pain and bleeding, these symptoms disappeared or were remarkably
      relieved. However, three patients had primary tumor progression at 7, 9, and 15
      months after irradiation with total doses of 56.8, 58.4, and 68.3 Gy in EQD2,
      respectively. Two of these patients had relapses of bleeding and pain. The
      primary progression-free rate considering all patients was 69% at 1 year and 34%
      at 2 years. The corresponding overall survival rates were 34% at 1 year, and 8%
      at 2 years, with an estimated median survival time of 7 months. The number of
      metastatic bone sites (p=0.027) and administration of chemotherapy (p<0.001) were
      significant prognostic factors for survival. CONCLUSION: Radiation therapy is
      effective for relief of pelvic symptoms in patients with bone metastasis from
      uterine cervical cancer. For patients who are expected to survive for more than 1
      year, almost curative-dose irradiation to primary tumors is recommended.

PMID- 29374738
TI  - Which Primary Organ Is Most Suitable for Performing Pulmonary Metastasectomy?
AB  - BACKGROUND/AIM: The aim of this study was to assess the appropriateness of
      pulmonary metastasectomy (MT), with a focus on the primary organ. PATIENTS AND
      METHODS: The pathological status of the primary organ, outcome of the MT, disease
      free interval, and overall survival were assessed. RESULTS: The primary organ was
      the most significant prognostic factor analyzed, with a relative risk of 4.6 (95%
      confidence interval: 1.69-12.56, p=0.003). Patients with colorectal carcinoma had
      a better survival than those with another primary organ (p=0.003). The hazard
      ratios by primary organ in comparison to colorectal carcinoma were 3.2 for head
      and neck carcinoma, 3.5 for soft tissue sarcoma, 8.3 for hepatocellular
      carcinoma, and 8.9 for urinary carcinoma. CONCLUSION: Colorectal carcinoma is
      associated with a greater survival benefit than cancer of other primary organs.
      Colorectal carcinoma cases should be more aggressively considered for MT than
      other primary organ cases.

PMID- 29374739
TI  - Long-term Favorable Outcomes of Radiofrequency Ablation for Hepatocellular
      Carcinoma as an Initial Treatment: A Single-center Experience Over a 10-Year
      Period.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is an alternative to hepatic resection
      and one of the major therapeutic options for hepatocellular carcinoma (HCC).
      Here, we investigated the long-term outcomes of RFA as an initial treatment for
      HCC. PATIENTS AND METHODS: From January 2000 to December 2014, we treated 1,043
      patients with RFA for HCC at the Kumamoto University Hospital; 327 of these
      patients (31.4%) were treated for primary HCC. After exclusion of 75 patients who
      underwent combined therapy, data for 252 patients were examined. We
      retrospectively analyzed the long-term outcomes of RFA and identified factors of
      poor prognosis. RESULTS: The median platelet count, prothrombin activity and
      indocyanine green retention rate at 15 min were 9.1*104/MUl, 83% and 26%,
      respectively. The 5-year overall survival (OS) rate was 69% and the median
      survival time was 7.0 years. The 5-year recurrence-free survival (RFS) rate was
      17%, and the median RFS was 2.0 years. A multivariate analysis revealed that age
      >80 years [hazard ratio (HR)=7.76, p=0.011], tumor diameter >2 cm (HR=1.68,
      p=0.047) and multiple tumors (HR=1.87, p=0.014) were independent prognostic
      factors for poor OS. For RFS, des-gamma-carboxy prothrombin (DCP) >=40 mAU/ml
      (HR=1.47, p=0.038) and multiple tumors (HR=1.63, p=0.0056) were independent
      prognostic factors. Local recurrence at the ablated site occurred in 33/252
      patients (13%), and in 33/372 tumors (8.9%). CONCLUSION: Although our cohort
      included patients with relatively worse liver function, a favorable 5-year
      survival rate 69% was obtained by RFA. DCP >=40 mAU/ml and multiple HCCs
      contribute to a higher risk of recurrence. Patients with these factors should
      therefore be followed-up intensively.

PMID- 29374740
TI  - Microvascular Invasion in Small-sized Hepatocellular Carcinoma: Significance for
      Outcomes Following Hepatectomy and Radiofrequency Ablation.
AB  - BACKGROUND/AIM: The significance of microvascular invasion (MVI) of
      hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA) is unknown.
      PATIENTS AND METHODS: We studied 149 patients with solitary small-sized HCC (<=3
      cm) who underwent hepatectomy, and developed a predictive model of MVI using
      independent factors related to the presence of MVI. The predictive model was
      applied to 159 patients who underwent RFA, and their outcomes were examined.
      RESULTS: A multivariate analysis revealed that alpha-fetoprotein >=15 ng/ml
      (relative risk (RR) 3.05, p=0.02), des-gamma-carboxy prothrombin >=100 mAU/ml (RR
      4.19, p=0.003), and tumor size >=2 cm (RR 3.37, p=0.03) were independent risk
      factors of MVI. Among the patients who underwent RFA, the survival in patients
      with risk factors 2-3 was significantly worse, and local recurrence was more
      frequently obserbed than those with 0-1. CONCLUSION: When an HCC tumor is
      expected to display MVI, RFA may not be suitable in terms of poorer survival and
      local disease-control rates.

PMID- 29374741
TI  - Visceral Adipose Tissue and Skeletal Muscle Index Distribution Predicts Severe
      Pancreatic Fistula Development After Pancreaticoduodenectomy.
AB  - BACKGROUND/AIM: In this study, we investigated the effect of body composition on
      pancreatic fistula (PF) development after pancreaticoduodenectomy (PD). MATERIALS
      AND METHODS: All consecutive patients with pancreatic and extrahepatic biliary
      malignancy following PD who were treated between 2006 and 2016 were enrolled.
      RESULTS: PF developed in 30.3% of cases (30/99 patients), including a grade B PF
      in 25.3% of cases (25/99 patients) and a grade C PF in 5.1% of cases (5/99
      patients). Univariate analysis identified that body mass index >=25 kg/m2,
      visceral adipose tissue area (VATA)/skeletal muscle index (SMI) >=2.0, pancreatic
      duct diameter <=3 mm, and drain amylase concentration (Amy) on postoperative day
      (POD) 1 >=5000 U/L were significantly associated with PF (grade B, C) after PD.
      Multivariate analysis indicated that VATA/SMI >=2.0 (p=0.009), pancreatic duct
      diameter <=3 mm (p=0.003), and drain Amy on POD1 >=5000 U/L (p=0.032) were
      independent risk factors for PF. CONCLUSION: Elevated VATA/SMI was the only
      preoperative key factor for PF after PD.

PMID- 29374742
TI  - Associations Between PET Textural Features and GLUT1 Expression, and the
      Prognostic Significance of Textural Features in Lung Adenocarcinoma.
AB  - BACKGROUND/AIM: We evaluated the association between positron emission tomography
      (PET) textural features and glucose transporter 1 (GLUT1) expression level and
      further investigated the prognostic significance of textural features in lung
      adenocarcinoma. PATIENTS AND METHODS: We evaluated 105 adenocarcinoma patients.
      We extracted texture-based PET parameters of primary tumors. Conventional PET
      parameters were also measured. The relationships between PET parameters and GLUT1
      expression levels were evaluated. The association between PET parameters and
      overall survival (OS) was assessed using Cox's proportional hazard regression
      models. RESULTS: In terms of PET textural features, tumors expressing high levels
      of GLUT1 exhibited significantly lower coarseness, contrast, complexity, and
      strength, but significantly higher busyness. On univariate analysis, the
      metabolic tumor volume, total lesion glycolysis, contrast, busyness, complexity,
      and strength were significant predictors of OS. Multivariate analysis showed that
      lower complexity (HR=2.017, 95%CI=1.032-3.942, p=0.040) was independently
      associated with poorer survival. CONCLUSION: PET textural features may aid risk
      stratification in lung adenocarcinoma patients.

PMID- 29374743
TI  - Circulating Tumor Cells Accurately Predicting Progressive Disease After Treatment
      in a Patient with Non-small Cell Lung Cancer Showing Response on Scans.
AB  - Lung cancer is the leading cause of cancer-related deaths worldwide. Most
      patients present with advanced inoperable disease. Traditionally, responses to
      treatments are evaluated using different imaging modalities, which can sometimes
      be confusing. This is particularly more relevant in stage 3 disease where, after
      radiation therapy, persistent tumors on scans can represent active disease or
      scar tissue. We have been evaluating role of circulating tumor cells (CTCs) in
      that setting. Here we present the case of a 68-year-old male with stage 3 disease
      whose primary tumor responded to chemoradiotherapy on imaging, but whose CTC
      count was higher than the pre-treatment value. The patient later developed liver
      metastases. In this case, the CTC count more accurately predicted the patient's
      prognosis and highlights the need for exploration of the CTC count as a tool
      supplemental to imaging modalities.

PMID- 29374744
TI  - Association Between Clinicopathological Features and Programmed Death Ligand 1
      Expression in Non-small Cell Lung Cancer.
AB  - BACKGROUND/AIM: Programmed cell death ligand 1 (PD-L1) expression is a predictive
      marker for immunotherapy effects in advanced non-small cell lung cancer (NSCLC),
      but its association with patient characteristics or specimens is controversial.
      We aimed to retrospectively analyze the association of PD-L1 expression with
      clinicopathological features of NSCLC patients. MATERIALS AND METHODS: The PD-L1
      expression and clinicopathological features of NSCLC patients were assessed from
      January 2017 to June 2017 in the Tokyo Metropolitan Cancer and Infectious
      Diseases Centre, Komagome Hospital were reviewed (n=108). RESULTS: For PD-L1
      expressions of 0% and >1%, multivariate analysis showed that lymph node sample
      results were associated with positive PD-L1 expression. Archival samples and high
      serum carcinoembryonic antigen (CEA) levels were associated with negative PD-L1
      expression. Sample preservation time and CEA levels correlated with PD-L1
      expression. CONCLUSION: Nodal metastasis, sample preservation time and CEA levels
      were associated with PD-L1 expression in NSCLC.

PMID- 29374745
TI  - Intensity and Pattern of Enhancement on CESM: Prognostic Significance and its
      Relation to Expression of Podoplanin in Tumor Stroma - A Preliminary Report.
AB  - BACKGROUND/AIM: It is possible that the degree of enhancement on contrast
      enhanced spectral mammography (CESM), a new diagnostic method, might provide
      prognostic information for breast cancer patients. Therefore, in a group of 82
      breast cancer patients, we analyzed the prognostic significance of degree and
      pattern of enhancement on CESM as well as its relation to: (a) breast cancer
      immunophenotype (based on ER/PR/HER2 status) (b) podoplanin expression in cancer
      stroma (lymphatic vessel density plus podoplanin-positivity of cancer-associated
      fibroblasts), and (c) other histological parameters. MATERIALS AND METHODS: For
      each tumor the intensity of enhancement on CESM was qualitatively assessed as
      strong or weak/medium, while the pattern - as homogenous and heterogenous.
      RESULTS: Herein we report, for the first time, that strong and heterogenous
      enhancement on CESM was related to unfavorable disease-free survival of breast
      cancer patients (p=0.005). Moreover, the strong enhancement was more frequent in
      large and node-positive tumors (pT>1, pN>0) (p=0.002), as well as in carcinomas
      with podoplanin-sparse stroma (p=0.008). CONCLUSION: Intensity and pattern of
      enhancement on CESM might provide (together with the results of other diagnostic
      imaging methods) not only the confirmation of presence or absence of tumor, but
      also prognostic information.

PMID- 29374746
TI  - Fibrinogen Levels Are Associated with Lymph Node Involvement and Overall Survival
      in Gastric Cancer Patients.
AB  - BACKGROUND/AIM: Combination of perioperative chemotherapy with gastrectomy with
      D2 lymphadenectomy improves long-term survival in patients with gastric cancer.
      The aim of this study was to investigate the predictive value of preoperative
      levels of CRP, albumin, fibrinogen, neutrophil-to-lymphocyte ratio and routinely
      used tumor markers (CEA, CA 19-9, CA 72-4) for lymph node involvement. MATERIALS
      AND METHODS: This retrospective study was conducted in 136 patients who underwent
      surgery between 2007 and 2015. Bivariable and multivariable analyses were
      performed in order to identify important characteristics associated with the risk
      of lymph node involvement. Kaplan-Meier survival curves and log-rank tests were
      used to compare overall survival. RESULTS: Lymph node involvement was
      significantly affected by preoperative fibrinogen (p=0.008) and albumin
      (p=0.023). Poor clinical condition, T and N staging and fibrinogen level above
      3.5 g/l were significantly associated with worse overall survival. CONCLUSION:
      Preoperative fibrinogen and albumin levels are significantly associated with
      lymphoid metastases in patients with gastric cancer.

PMID- 29374747
TI  - Is Ki-67 of Diagnostic Value in Distinguishing Between Partial and Complete
      Hydatidiform Moles? A Systematic Review and Meta-analysis.
AB  - BACKGROUND/AIM: To demonstrate the value of Ki-67 in distinguishing between
      partial and complete hydatidiform moles. MATERIALS AND METHODS: We searched
      electronic databases included Medline, WOK, Cochrane Library and CNKI, through
      January 24, 2015. Experts were consulted, and references from related articles
      were examined. The meta-analysis was conducted with RevMan5.3, according to the
      PRISMA guidelines. Mantel-Haenszel estimates were calculated and pooled under a
      random effect model, with data expressed as odds ratio (OR) and 95% confidence
      interval (CI). RESULTS: We analyzed eight trials with a total of 337 participants
      who underwent uterine curettage and met the inclusion criteria. A significantly
      higher expression of Ki-67 was observed in complete than in partial hydatidiform
      moles (OR=3.28; 95%CI=1.80-5.96; p<0.0001). CONCLUSION: The Ki-67 expression was
      higher in complete than in partial hydatidiform moles. Therefore, Ki-67 may be of
      diagnostic value in distinguishing between partial and complete hydatidiform
      moles. However, the present study had only a limited number of samples, so
      investigation of a greater number of cases is needed to confirm this conclusion.

PMID- 29374748
TI  - A Critical Appraisal of the Recent Reports on Sunbeds from the European
      Commission's Scientific Committee on Health, Environmental and Emerging Risks and
      from the World Health Organization.
AB  - The European Commission's Scientific Committee on Health, Environmental and
      Emerging Risks and the World Health Organization recently published reports which
      concluded that a large proportion of melanoma and non-melanoma skin cancer is
      attributable to sunbed use, and that there is no need to use sunbeds as there are
      no health benefits and they are not needed to achieve an optimal vitamin D level.
      The overall conclusion from both bodies was that there is no safe limit for UV
      irradiance from sunbeds. We are, however, deeply concerned that these assessments
      appear to be based on an incomplete, unbalanced and non-critical evaluation of
      the literature. Therefore, we rebut these conclusions by addressing the
      incomplete analysis of the adverse health effects of UV and sunbed exposure (what
      is 'safe'?) and the censored representation of beneficial effects, not only but
      especially from vitamin D production. The stance taken by both agencies is not
      sufficiently supported by the data and in particular, current scientific
      knowledge does not support the conclusion sunbed use increases melanoma risk.

PMID- 29374749
TI  - A Review of the Evidence Supporting the Vitamin D-Cancer Prevention Hypothesis in
      2017.
AB  - The vitamin D-cancer prevention hypothesis has been evaluated through several
      types of studies, including geographical ecological studies related to indices of
      solar ultraviolet-B (UVB) dose (the primary source of vitamin D for most people),
      observational studies related to UVB exposure or serum 25-hydroxyvitamin D
      [25(OH)D] concentrations, laboratory studies of mechanisms, and clinical trials.
      Each approach has strengths and limitations. Ecological studies indirectly
      measure vitamin D production and incorporate the assumption that vitamin D
      mediates the effect of UVB exposure. Findings from observational studies with
      long follow-up times are affected by changing 25(OH)D concentrations over time.
      Most clinical trials have been poorly designed and conducted, based largely on
      guidelines for pharmaceutical drugs rather than on nutrients. However, three
      clinical trials do support the hypothesis. In general, the totality of the
      evidence, as evaluated using Hill's criteria for causality in a biological
      system, supports the vitamin D-cancer prevention hypothesis.

PMID- 29374750
TI  - Analytical Methods for Quantification of Vitamin D and Implications for Research
      and Clinical Practice.
AB  - A plethora of contradictory research surrounds vitamin D and its influence on
      health and disease. This may, in part, result from analytical difficulties with
      regard to measuring vitamin D metabolites in serum. Indeed, variation exists
      between analytical techniques and assays used for the determination of serum 25
      hydroxyvitamin D. Research studies into the effects of vitamin D on clinical
      endpoints rely heavily on the accurate assessment of vitamin D status. This has
      important implications, as findings from vitamin D-related studies to date may
      potentially have been hampered by the quantification techniques used. Likewise,
      healthcare professionals are increasingly incorporating vitamin D testing and
      supplementation regimens into their practice, and measurement errors may be also
      confounding the clinical decisions. Importantly, the Vitamin D Standardisation
      Programme is an initiative that aims to standardise the measurement of vitamin D
      metabolites. Such a programme is anticipated to eliminate the inaccuracies
      surrounding vitamin D quantification.

PMID- 29374751
TI  - Vitamin D: Current Guidelines and Future Outlook.
AB  - Vitamin D is of public health interest because its deficiency is common and is
      associated with musculoskeletal diseases, as well as extraskeletal diseases, such
      as cancer, cardiovascular diseases, and infections. Several health authorities
      have reviewed the existing literature and published nutritional vitamin D
      guidelines for the general population. There was a wide consensus that serum 25
      hydroxyvitamin D [25(OH)D] concentration should be used to assess vitamin D
      status and intake, and that musculoskeletal, and not extraskeletal, effects of
      vitamin D should be the basis for nutritional vitamin D guidelines. Recommended
      target levels for 25(OH)D range from 25 to 50 nmol/l (10 to 20 ng/ml),
      corresponding to a vitamin D intake of 400 to 800 International Units (10 to 20
      MUg) per day. It is of concern that significant sections of the general
      population do not meet these recommended vitamin D levels. This definitely
      requires action from a public health perspective.

PMID- 29374752
TI  - Photocarcinogenesis and Skin Cancer Prevention Strategies: An Update.
AB  - UV radiation is acknowledged as the primary cause of photocarcinogenesis and
      therefore contributes to the development of skin cancer entities such as squamous
      cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma. Typical DNA
      photoproducts and indirect DNA damage caused by reactive oxygen species are the
      result of UV radiation. UV-induced DNA damage is repaired by nucleotide excision
      repair, which consequently counteracts the development of mutations and skin
      carcinogenesis. Tumour-suppressor genes are inactivated by mutation and growth
      promoting pathways are activated leading to disruption of cell-cycle progression.
      Depending on the skin cancer entity, some genes are more frequently affected than
      others. In BCC mutations in Patched or Smoothened are common and affect the Sonic
      hedgehog pathway. In SCC, cell regulator protein p53 (TP53) mutations are
      prevalent, as well as mutations of the epidermal growth factor receptor (EGFR),
      cyclin-dependent kinase 2A (CDKN2A), Rat sarcoma (RAS), or the tyrosine kinase
      Fyn (FYN). UV-induced mutations in TP53 and CDKN2A are frequent in melanoma. UV
      induced inflammatory processes also facilitate photocarcinogenesis. Recent
      studies showed a connection between photocarcinogenesis and citrus consumption,
      phytochemicals, alcohol consumption, hormone replacement therapy, as well as oral
      contraceptive use. Preventative measures include adequate use of sun protection
      and skin cancer screening at regular intervals, as well as the use of
      chemopreventative agents.

PMID- 29374753
TI  - Xeroderma Pigmentosum - Facts and Perspectives.
AB  - Ultraviolet (UV)-induced DNA lesions are almost exclusively removed by the
      nucleotide excision repair (NER) pathway, which is essential for prevention of
      skin cancer development. Patients with xeroderma pigmentosum (XP) are extremely
      sun sensitive due to a genetic defect in components of the NER cascade. They
      present with first signs of premature skin aging at an early age, with a
      considerably increased risk of developing UV-induced skin cancer. XP belongs to
      the group of DNA repair defective disorders that are mainly diagnosed in the
      clinic and in hindsight confirmed at the molecular level. Unfortunately, there
      are no causative treatment options for this rare, autosomal-recessive disorder,
      emphasizing the importance of an early diagnosis. Subsequently, UV-protective
      measures such as the reduction of exposure to environmental UV and regular skin
      cancer screenings should be undertaken to substantially improve prognosis as well
      as the disease course.

PMID- 29374754
TI  - The Impact of UV-dose, Body Surface Area Exposed and Other Factors on Cutaneous
      Vitamin D Synthesis Measured as Serum 25(OH)D Concentration: Systematic Review
      and Meta-analysis.
AB  - BACKGROUND/AIM: To optimize public health campaigns concerning UV exposure, it is
      important to characterize factors that influence UV-induced cutaneous vitamin D
      production. This systematic review and meta-analysis investigated the impact of
      different individual and environmental factors including exposed body surface
      area (BSA), UVB dose and vitamin D status, on serum 25(OH)D concentration.
      MATERIALS AND METHODS: In accordance with Preferred Reporting Items for
      Systematic Reviews and Meta-analyses, and Meta-analysis of Observational studies
      in Epidemiology guidelines, a systematic literature search was conducted
      (MEDLINE; 01/1960-07/2016) investigating the impact of these factors on vitamin D
      status after artificial UV exposure as main outcome measure. Summary mean
      differences [and 95% confidence interval (CI)] were derived from random-effects
      meta-analysis to account for possible heterogeneity across studies. Meta
      regression was conducted to account for impact of UVB dose, baseline 25(OH)D
      level and BSA. RESULTS: We identified 15 studies, with an estimated mean 25(OH)D
      rise per standard erythema dose (SED) of 0.19 nmol/l (95% CI 0.11-0.26 nmol/l).
      Results from meta-regression suggest a significant impact of UV dose and baseline
      25(OH)D concentration on serum 25(OH)D level (p<0.01). Single UVB doses between
      0.75 and 3 SED resulted in the highest rise of serum 25(OH)D per dose unit. BSA
      exposed had a smaller, non-proportional, not significant impact. Partial BSA
      exposure resulted in relatively higher rise compared to whole-body exposure (e.g.
      exposure of face and hands caused an 8-fold higher rise of serum 25(OH)D
      concentration/SED/1% BSA compared to whole-body exposure). Our findings support
      previous reports, estimating that the half-life of serum 25(OH)D varies depending
      on different factors. CONCLUSION: Our results indicate that partial BSA exposure
      (e.g. 10%) with moderate UV doses (e.g. 1 SED) is effective in generating or
      maintaining a healthy vitamin D status. However, due to limitations that include
      possible confounding factors such as skin type, which could not be considered,
      these findings should be interpreted with caution.

PMID- 29374755
TI  - The Winding Path Towards an Inverse Relationship Between Sun Exposure and All
      cause Mortality.
AB  - For a long time, skin cancer has been known to be related to extensive UV
      exposure. New emerging data have, however, shown low UV exposure/low vitamin D
      levels to be related to increased mortality rate due to skin cancer. In addition,
      low sun exposure habits in regions of low solar intensity have been shown to be a
      major risk factor for all-cause mortality in the same range as that for smoking.
      This is mainly due to lower all-cause mortality due to cardiovascular disease
      (CVD) and non-CVD/non-cancer disease among women with active sun exposure. Women
      with active sun exposure habits were estimated to have a 1- to 2-year longer life
      expectancy during the Melanoma in Southern Sweden study interval. These findings
      are in line with those to be expected from an evolutionary perspective and
      research findings, but in opposition to present guidelines and recommendations.

PMID- 29374756
TI  - Vitamin D Status, Supplementation and Cardiovascular Disease.
AB  - This review was conducted to assess the dose-response relationship between
      vitamin D and cardiovascular disease (CVD) outcomes in humans: Prospective cohort
      studies indicate a multivariable-adjusted non-linear increase in CVD events at
      levels of circulating 25-hydroxyvitamin D [25(OH)D] of less than 50 nmol/l.
      However, Mendelian randomization studies do not support these findings. Although
      meta-analyses of randomized controlled trials (RCTs) do not rule out small
      beneficial vitamin D effects on surrogate parameters of CVD risk, such as
      arterial stiffness, at vitamin D doses equivalent to 1,000-5,333 IU daily, other
      meta-analyses of RCTs show no reduction in CVD events by vitamin D
      supplementation. Notably, some cohort studies and a recent RCT provide evidence
      for harmful effects of vitamin D on CVD outcomes at 25(OH)D levels in excess of
      100 nmol/l. In conclusion, more studies in individuals with a deficient 25(OH)D
      level (i.e. <30 nmol/l) are needed, but caution is necessary regarding
      supplementation with vitamin D doses achieving a 25(OH)D level which exceeds 100
      nmol/l.

PMID- 29374757
TI  - Solarium Use and Risk for Malignant Melanoma: Meta-analysis and Evidence-based
      Medicine Systematic Review.
AB  - BACKGROUND: There is an ongoing debate whether solarium use (indoor
      tanning/artificial UV) may increase the risk for primary cutaneous malignant
      melanoma. AIM: A systematic literature search was conducted using MEDLINE and ISI
      Web of Science. Included studies were critically assessed regarding their risk of
      bias, and methodological shortcomings. Levels of evidence and grades of
      recommendation were determined according to guidelines of the Oxford Centre for
      Evidence-Based Medicine. Summary risk estimates and 95% confidence intervals for
      four different outcomes (ever exposure, exposure at younger age, high/low
      exposure vs. non-exposure) were derived from random-effects meta-analyses to
      account for possible heterogeneity across studies. RESULTS: Two cohort and twenty
      nine case-control studies were eligible. Overall, quality of included studies was
      poor as a result of severe limitations, including possible recall and selection
      bias, and due to lack of interventional trials. Summary risk estimates suggested
      a weak association (odds ratio (OR)=1.19, 95% confidence interval (CI)=1.04-1.35,
      p=0.009) for ever-exposure to UV radiation from a solarium with melanoma risk.
      However, sensitivity analyses did not show an association for studies from Europe
      (OR=1.10; 95%CI=0.95-1.27, p=0.218), studies with low risk of bias (OR=1.15;
      95%CI=0.94-1.41, p=0.179), and studies conducted after 1990 (OR 1.09; 95%CI=0.93
      1.29, p=0.295). Moreover, moderate associations were found for first exposure to
      UV radiation from a solarium at younger age (<25 years) and high exposure (>10
      sessions in lifetime) with melanoma risk. However, for all outcomes analyzed,
      overall study quality and resulting levels of evidence (3a-) and grades of
      recommendation (D) were low due to lack of interventional studies and severe
      limitations including unobserved or unrecorded confounding. CONCLUSION: Current
      scientific knowledge is mainly based on observational studies with poor quality
      data, which report associations but do not prove causality. At present, there is
      no convincing evidence that moderate/responsible solarium use increases melanoma
      risk.

PMID- 29374758
TI  - Effects of Combined Treatment with Vitamin D and COX2 Inhibitors on Breast Cancer
      Cell Lines.
AB  - BACKGROUND: Vitamin D is known for its anticancer potential. Prostaglandin E2
      (PGE2) is a proliferative and inflammation-activating agent. The production of
      PGE2 is dependent on the activity of cyclooxygenase-2 (COX2). A link between
      vitamin D and PGE2 metabolism was shown recently. MATERIALS AND METHODS: In MDA
      MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of
      calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as
      well as on the protein and mRNA expression of COX2 using western blot and
      quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The
      proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the
      COX2 inhibitor celecoxib and even more strongly by their combination. Moreover,
      calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2
      mRNA expression in both cell lines. CONCLUSION: The combination of calcitriol and
      celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer
      cell lines.

PMID- 29374759
TI  - Tandem Affinity Purification and Nano HPLC-ESI-MS/MS Reveal Binding of Vitamin D
      Receptor to p53 and other New Interaction Partners in HEK 293T Cells.
AB  - While nuclear cofactors that contribute to vitamin D receptor (VDR)-mediated gene
      transcription, including retinoid X receptors, nuclear co-activators and co
      repressors, have been extensively investigated, little is known about cytoplasmic
      VDR-binding partners and the physiological relevance of their interaction. To
      gain new insight into this topic, we isolated whole-cell protein extracts of 1,25
      dihydroxyvitamin D3 stimulated and UV-B-irradiated vs. non-irradiated HEK 293T
      cells transfected with a plasmid called pURB VDR C-Term TAP tag. VDR complex was
      purified by tandem affinity purification (TAP). The nuclear tumor-suppressor
      protein p53 and its negative regulator novel INHAT repressor (NIR), in addition
      to 43 other nuclear or cytoplasmatic VDR binding partners, were identified using
      nano high-performance liquid chromatography-electrospray ionization tandem mass
      spectrometric analysis. VDR binding to p53 was confirmed by western blot
      analysis. Future studies are required to further elucidate the functional
      significance of these interactions.

PMID- 29374760
TI  - Partial Body UV Exposure in Chronic Kidney Disease and Extrarenal Vitamin D
      Metabolism.
AB  - BACKGROUND/AIM: Exposure of the skin to sunshine is the major natural source of
      vitamin D. In order to imitate this natural production of vitamin D for patients
      with chronic kidney disease, hemodialysis patients were exposed three times a
      week to radiation of the front part of both legs to normalize the vitamin D
      status. PATIENTS AND METHODS: Partial body UVB irradiation was performed during
      the routine dialysis session. Twenty-two patients took part, with a mean age of
      61.7 (range=35-81) years. RESULTS: Serum levels of 25(OH)D3 and 1,25(OH)2D3
      increased into the mid normal range. Intact parathyroid hormone decreased by 25%
      and osteocalcin by 45%. 24-Hour blood-pressure monitoring demonstrated decreases
      in systolic and diastolic blood pressure. CONCLUSION: Partial body exposure to
      UVB radiation normalized not only the serum level of 25(OH)D3, but also that of
      1,25(OH)2D3, which resulted in a significant decrease in parathyroid hormone,
      osteocalcin levels, and also in blood pressure. Sunshine imitating UVB exposure
      utilizes the capacity of the skin to convert extrarenally vitamin D3 to 25(OH)D3
      and 1,25(OH)2D3.

PMID- 29374761
TI  - Borderline positive antineutrophil cytoplasmic antibodies (ANCA)-PR3/MPO
      detection in a large cohort tertiary center: lessons learnt from a real-life
      experience.
AB  - BACKGROUND: Enzyme-linked immunosorbent assay (ELISA) and indirect
      immunofluorescence (IIF) are the best strategies for antineutrophil cytoplasmic
      antibodies (ANCA) detection. In a minority of subjects, ELISA-based ANCA testing
      may result in a borderline positive titre. Therefore, we assessed the clinical
      significance of such a result. METHODS: This is a retrospective study, which
      included all subjects screened for ANCA subtypes (myeloperoxidase (MPO) or
      proteinase-3 (PR3)) with subsequent identification of borderline positive
      results, as determined by ELISA and retested using IIF. The demographic, clinical
      and laboratory data of subjects with borderline positive ANCA test results were
      extracted from their medical records. RESULTS: A total of 14,555 PR3/MPO-ANCA
      tests were performed with ELISA during the study period (2006-2016). Of the
      14,555 PR3-ANCA antibody tests that were performed, 94 were borderline positive
      (titre 0.9-1.1), and of 14,555 MPO-ANCA antibody tests, 43 were borderline
      positive (titre 0.9-1.1). The male-to-female ratio was 1:1.08 and the mean age
      was 50.95+/-21.79 years. Four MPO-ANCA (9.30%) and 11 PR3-ANCA (11.70%) antibody
      borderline samples resulted positive on IIF testing. Subjects with borderline
      positive MPO-ANCA were found to have a poorer outcome in terms of renal failure
      and the requirement of dialysis. CONCLUSIONS: Subjects with borderline positive
      MPO-ANCA and positive p-ANCA (IIF) seem to have a less favorable outcome.
      Physicians should be aware of these findings and possibly perform a closer follow
      up and routine screening for these subjects.

PMID- 29374762
TI  - Late presentation of glycogen storage disease types Ia and III in children with
      short stature and hepatomegaly.
AB  - BACKGROUND: Glycogen storage diseases (GSDs) are a collection of disorders
      related to glycogen synthesis or degradation that classically present in infancy
      with hypoglycemia, failure to thrive and hepatomegaly; however, their phenotype
      can vary significantly. CASE PRESENTATION: We present the cases of two children,
      5 years old and 3.5 years old, who were referred to endocrinology for short
      stature. They were ultimately found to have hepatomegaly, fasting hypoglycemia,
      mild elevation of transaminases and ketosis. Laboratory and genetic studies were
      consistent with double heterozygosity for GSDs Ia and III, with one novel
      mutation discovered in each patient. Nightly, both children were treated with
      cornstarch, which resulted in resolution of laboratory abnormalities and
      improvement in their growth velocity. These cases are unusual in that GSD was
      diagnosed relatively late in life in patients with no previous history of severe
      hypoglycemia. CONCLUSIONS: They highlight the importance of considering glycogen
      storage disease in a child presenting with short stature, as it is a treatable
      disease that can be diagnosed non-invasively with genetic testing.

PMID- 29374763
TI  - Ultrasonographic assessment of pubertal breast development in obese children:
      compliance with the clinic.
AB  - BACKGROUND: The aim of the study was to determine the compliance with the
      clinical and ultrasonographic staging of pubertal breast development in obese
      children. METHODS: Fifty-two obese children with Tanner stage 2 and stage 3
      breast development accompanied by at least one pubertal clinical finding were
      included in the study. The staging of breast development was also performed
      according to the ultrasonographic morphostructural appearance. The subjects were
      then divided into subgroups according to their clinical and ultrasonographic
      breast stages. The stages given by both methods were compared for consistency
      with the hormonal values and other radiological (uterus long diameter, ovary
      sizes) findings. RESULTS: The correlation between the clinical and
      ultrasonographic staging of pubertal breast development was determined to be weak
      (r=0.19). Estradiol levels, uterus long diameter and ovary sizes were
      significantly increased when the ultrasonographic stage increased among the
      subjects with clinically similar breast development stage. However, no
      statistical difference was determined in these parameters among the subjects with
      ultrasonographically similar but clinically different breast development.
      CONCLUSIONS: It was shown that the ultrasonographic staging of breast development
      could provide more accurate and objective data due to the possible mistakes
      caused in the breast development staging of obese children by their adipose
      tissue.

PMID- 29374765
TI  - Teaching removable partial denture design: 'METACIEL', a novel digital procedure.

PMID- 29374764
TI  - Perception of educational environment among medical students in Thailand.
AB  - Objectives: To examine the perception of educational environment among clinical
      year students in Thailand using Dundee ready education environment measure
      (DREEM) and identify factors associated with the DREEM scores. Methods: A total
      of 2,467 fourth- to sixth-year students from 34 teaching hospitals nationwide
      responded to a Thai version of DREEM questionnaire. Data on each student's sex,
      year of study, size of teaching hospitals and GPAX were collected. Mean total
      DREEM scores and subscales were calculated and then compared across groups using
      t-test and one-way ANOVA. Results: The overall student perception on educational
      environment was 'more positive than negative,' with the mean total DREEM score of
      131.1 (SD=17.4). Similar findings were observed in all subscales. Mean total
      DREEM scores were lower in medium-size than small- and large-size teaching
      hospitals 129.9 (SD = 18.1), 131.9 (SD = 17.5) and 131.6 (SD=16.4) respectively
      (F (2,2422)=3.21, p=0.04). Sex and years of study was associated with certain
      DREEM subscales. Conclusions: Clinical year medical students in Thailand were
      satisfied with their academic learning environment, with varying perceptions
      across different size of teaching hospitals. Repeat assessment of educational
      environment of medical schools over time is needed for monitoring changes after
      specific educational interventions being applied.

PMID- 29374766
TI  - 2017 Kermanshah Earthquake; Lessons Learned.

PMID- 29374767
TI  - Usnic Acid Induces Cycle Arrest, Apoptosis, and Autophagy in Gastric Cancer Cells
      In Vitro and In Vivo.
AB  - BACKGROUND Usnic acid (UA), a secondary metabolite, is mainly derived from
      certain lichen species. Growing evidence suggests that UA has antitumor, anti
      oxidative, anti-inflammatory, and other activities in a variety of cancer cells.
      However, the antitumor effect of UA in gastric cancer cells (GC) is unclear. The
      aim of this investigation was to assess the antitumor effect of UA in GC cells in
      vitro and in vivo, and to explore the underlying mechanisms. MATERIAL AND METHODS
      Cell proliferation was measured by CCK8 assay, the arrest of cell cycle was
      assessed by flow cytometry, and cellular apoptosis was observed via Hoechst 33258
      staining assay. Expression levels of apoptosis-related proteins (activated
      caspase-3 and PARP, Bax, Bcl2) and autophagy-associated proteins (LC3-II and p62)
      were verified through Western blot analysis. H&E staining and
      immunohistochemistry were carried out in the subcutaneously implanted BGC823
      tumor model in a nude mouse experiment. RESULTS In vitro, we demonstrated that UA
      was significantly effective in inducing morphological changes, inhibiting the
      cell proliferation dose- and time-dependently, arresting the cell cycle phase,
      promoting cancer cellular apoptosis, and inducing autophagy activity. In vivo,
      compared to mice treated with 5-FU alone, UA treatment was significantly more
      effective in suppressing the tumor growth without affecting body weight, and in
      regulating the amount of Bax and Bcl2 in tumor tissues. CONCLUSIONS UA induces
      cell cycle arrest and autophagy and exerts anti-proliferative and apoptotic
      effects by modulating expression of apoptosis-related proteins in stomach
      neoplasm cells, and has a better antitumor effect compared to 5-Fu in the
      xenograft model.

PMID- 29374768
TI  - Screening of Potential Genes and Transcription Factors of Postoperative Cognitive
      Dysfunction via Bioinformatics Methods.

PMID- 29374769
TI  - Fournier's Gangrene: Clinical Presentation of 13 Cases.
AB  - BACKGROUND Fournier's gangrene (FG) is a fulminant form of infective,
      polymicrobial, necrotizing fasciitis of the perineal, genital, and perianal
      regions. It commonly affects men, but women and children may also develop this
      type of tissue necrosis. MATERIAL AND METHODS This study is a retrospective
      analysis of the management of 13 cases of Fournier's gangrene, diagnosed from
      among about 45 000 patients (men, women, and children) treated in the Department
      of General, Oncological, and Functional Urology (Medical University of Warsaw)
      from 1995 to 2013. All patients with Fournier's gangrene underwent adequate
      surgical debridement of the necrotic tissues. Additional procedures (suprapubic
      cystostomy and orchiectomy) were necessary in 10 out of 13 (77.0%) patients.
      Seven out of 13 (53.8%) patients required subsequent reconstructive surgery of
      the scrotum. RESULTS All 13 patients were males, with a median age of 59.6 years
      (range: 42-68 years). The average hospital stay was 31.9 days (range: 16-46
      days). None of our patients died due to Fournier's gangrene. Bacteriological
      cultures of samples from the wounds showed polymicrobial flora, including the
      following genera of aerobes and anaerobes: Escherichia, Proteus, Klebsiella,
      Moraxella, Gemella, Enterococcus, Streptococcus, Staphylococcus, Bacteroides,
      Pseudoflavonifractor, Parabacteroides, Porphyromonas, Prevotella, Peptoniphilus,
      Peptostreptococcus, Actinomyces, Collinsella, and Lactobacillus. CONCLUSIONS
      Favorable outcome of FG treatment with low morbidity and no mortality can be
      achieved with rapid diagnosis, urgent surgical debridement of all necrotic
      tissues, and broad-spectrum empirical antimicrobial therapy, usually with
      combined antibiotics, against aerobic and anaerobic bacteria. Prevention of
      uroseptic shock by treating localized infection is compulsory.

PMID- 29374770
TI  - A Comparison of Concentrations and Congener Patterns of Polybrominated Diphenyl
      Ethers in Seasonally Sampled Outdoor Air from a Farmland Area in Guangzhou, South
      China.
AB  - To investigate the concentration and congener patterns of polybrominated diphenyl
      ethers (PBDE) in outdoor air from farmland area, air samples were collected using
      passive and active sample methods from April to November 2012, in an e-waste
      dismantling town in the Guangzhou region of South China. The sum of gaseous and
      particulate PBDE concentrations averaged 74.26 pg/m3 and ranged between 3.24 and
      247.30 pg/m3, while the mean gaseous and particulate PBDEs were 19.20 and 55.07
      pg/m3, respectively. The PBDE level was comparable to those in urban air of non
      electric waste areas, but much lower than those in both indoor and outdoor air of
      e-waste dismantling workshop area. Dominant congeners were BDE-47 and BDE-28 for
      the gaseous phase and BDE-209 and BDE-99 for the particulate phase. Relationship
      analysis showed that soil PBDEs were more significantly correlated with passive
      samples than with active samples, indicating that passive sample pattern could
      capture the accumulative effect of the sampling period and better represent the
      extent of soil contamination.

PMID- 29374771
TI  - Lower risk of hip fractures among Swedish women with large hips?
AB  - : In women, a large hip circumference (HC) related to lower hip fracture risk,
      independent of age and regardless if HC was measured long before or closer to the
      fracture. In older women, body mass index (BMI) explained the protection.
      INTRODUCTION: In postmenopausal women, HC has been suggested to inversely
      associate with hip fracture while this has not been investigated in middle-aged
      women. We examined the association between HC, measured at two different time
      points, and hip fracture in a Swedish female population-based sample monitored
      for incident hip fractures over many years. METHODS: Baseline HC, measured in
      1968 or 1974 (n = 1451, mean age 47.6 years), or the HC measures that were the
      most proximal before event or censoring (n = 1325, mean age 71.7 years), were
      used to assess the effects of HC on hip fracture risk in women participating in
      the Prospective Population Study of Women in Gothenburg. HC was parameterized as
      quintiles with the lowest quintile (Q1) as reference. Incident hip fractures over
      45 years of follow-up (n = 257) were identified through hospital registers.
      RESULTS: Higher quintiles of HC at both baseline and proximal to event were
      inversely associated with hip fracture risk in age-adjusted models, but only
      baseline HC predicted hip fractures independently of BMI and other covariates (HR
      (95% CI) Q2, 0.85 (0.56-1.27); Q3, 0.59 (0.36-0.96); Q4, 0.57 (0.34-0.96); Q5,
      0.58 (0.31-1.10)). CONCLUSIONS: A large HC is protective against hip fracture in
      midlife and in advanced age, but the association between proximal HC and hip
      fracture was explained by concurrent BMI suggesting that padding was not the main
      mechanism for the association. The independent protection seen in middle-aged
      women points to other mechanisms influencing bone strength.

PMID- 29374772
TI  - A kinetic view of acid-mediated tumor invasion.
AB  - According to the acid-mediated tumor invasion hypothesis, tumor-induced
      alteration of microenvironmental pH may provide a simple, yet complete mechanism
      for tumor invasion. The acid-mediation hypothesis analyzes the tumor growth and
      invasion process from a reaction-diffusion system perspective, where it
      incorporates the H+ ion concentration as a reaction factor and adds density
      dependent diffusion parameters to the reaction terms, yielding independent
      reaction-diffusion equations for the normal, tumor, and acid populations. In this
      article, we apply the dynamical stability theory to the acid-mediation
      hypothesis. For reasonable biological parameters, we study the fixed points
      central to the model and their stability by calculating the eigenvalues of the
      Jacobian matrix of the partial differential equations that represent how these
      three populations evolve with time. For the case where a malignant behavior has
      not already taken place yet (the time rates of change of the densities of the
      three populations are equal to zero), our numerical results convey two different,
      yet possible configurations in three-dimensional space: stable and unstable
      dynamical equilibriums, and we discuss possible prospective trajectories for the
      normal and tumor populations starting from each configuration. Moreover, we
      discuss potential applications of our approach.

PMID- 29374773
TI  - Palliative cares and the intensivist: not confined to the intensive care unit.

PMID- 29374774
TI  - The ALK receptor in sympathetic neuron development and neuroblastoma.
AB  - The ALK gene encodes a tyrosine kinase receptor characterized by an expression
      pattern mainly restricted to the developing central and peripheral nervous
      systems. In 2008, the discovery of ALK activating mutations in neuroblastoma, a
      tumor of the sympathetic nervous system, represented a breakthrough in the
      understanding of the pathogenesis of this pediatric cancer and established
      mutated ALK as a tractable therapeutic target for precision medicine. Subsequent
      studies addressed the identity of ALK ligands, as well as its physiological
      function in the sympathoadrenal lineage, its role in neuroblastoma development
      and the signaling pathways triggered by mutated ALK. This review focuses on these
      different aspects of the ALK biology and summarizes the various therapeutic
      strategies relying on ALK inhibition in neuroblastoma, either as monotherapies or
      combinatory treatments.

PMID- 29374775
TI  - Serogroup-level resolution of the "Super-7" Shiga toxin-producing Escherichia
      coli using nanopore single-molecule DNA sequencing.
AB  - DNA sequencing and other DNA-based methods are now broadly used for detection and
      identification of bacterial foodborne pathogens. For the identification of
      foodborne bacterial pathogens, taxonomic assignments must be made to the species
      or even subspecies level. Long-read DNA sequencing provides finer taxonomic
      resolution than short-read sequencing. Here, we demonstrate the potential of long
      read shotgun sequencing obtained from the Oxford Nanopore Technologies (ONT)
      MinION single-molecule sequencer, in combination with the Basic Local Alignment
      Search Tool (BLAST) with custom sequence databases, for foodborne pathogen
      identification. A library of mixed DNA from strains of the "Super-7" Shiga toxin
      producing Escherichia coli (STEC) serogroups (O26, O45, O103, O111, O121, O145,
      and O157[:H7]) was sequenced using the ONT MinION resulting in 44,245 long-read
      sequences. The ONT MinION sequences were compared to a custom database composed
      of the E. coli O-antigen gene clusters. A vast majority of the sequence reads
      were from outside of the O-antigen cluster and did not align to any sequences in
      the O-antigen database. However, 58 sequences (0.13% of the total sequence reads)
      did align to a specific Super-7 O-antigen gene cluster, with each O-antigen
      cluster aligning to at least four sequence reads. BLAST analysis against a custom
      whole-genome database revealed that 5096 (11.5%) of the MinION sequence reads
      aligned to one and only one sequence in the database, of which 99.6% aligned to a
      sequence from a "Super-7" STEC. These results demonstrate the ability of the
      method to resolve STEC to the serogroup level and the potential general utility
      of the MinION for the detection and typing of foodborne pathogens.

PMID- 29374776
TI  - Decoding auditory spatial and emotional information encoding using multivariate
      versus univariate techniques.
AB  - Emotion can have diverse effects on behaviour and perception, modulating function
      in some circumstances, and sometimes having little effect. Recently, it was
      identified that part of the heterogeneity of emotional effects could be due to a
      dissociable representation of emotion in dual pathway models of sensory
      processing. Our previous fMRI experiment using traditional univariate analyses
      showed that emotion modulated processing in the auditory 'what' but not 'where'
      processing pathway. The current study aims to further investigate this
      dissociation using a more recently emerging multi-voxel pattern analysis
      searchlight approach. While undergoing fMRI, participants localized sounds of
      varying emotional content. A searchlight multi-voxel pattern analysis was
      conducted to identify activity patterns predictive of sound location and/or
      emotion. Relative to the prior univariate analysis, MVPA indicated larger
      overlapping spatial and emotional representations of sound within early secondary
      regions associated with auditory localization. However, consistent with the
      univariate analysis, these two dimensions were increasingly segregated in late
      secondary and tertiary regions of the auditory processing streams. These results,
      while complimentary to our original univariate analyses, highlight the utility of
      multiple analytic approaches for neuroimaging, particularly for neural processes
      with known representations dependent on population coding.

PMID- 29374777
TI  - Single cell analysis of Crohn's disease patient-derived small intestinal
      organoids reveals disease activity-dependent modification of stem cell
      properties.
AB  - BACKGROUND: Intestinal stem cells (ISCs) play indispensable roles in the
      maintenance of homeostasis, and also in the regeneration of the damaged
      intestinal epithelia. However, whether the inflammatory environment of Crohn's
      disease (CD) affects properties of resident small intestinal stem cells remain
      uncertain. METHODS: CD patient-derived small intestinal organoids were
      established from enteroscopic biopsy specimens taken from active lesions (aCD
      SIO), or from mucosa under remission (rCD-SIO). Expression of ISC-marker genes in
      those organoids was examined by immunohistochemistry, and also by microfluid
      based single-cell multiplex gene expression analysis. The ISC-specific function
      of organoid cells was evaluated using a single-cell organoid reformation assay.
      RESULTS: ISC-marker genes, OLFM4 and SLC12A2, were expressed by an increased
      number of small intestinal epithelial cells in the active lesion of CD. aCD-SIOs,
      rCD-SIOs or those of non-IBD controls (NI-SIOs) were successfully established
      from 9 patients. Immunohistochemistry showed a comparable level of OLFM4 and
      SLC12A2 expression in all organoids. Single-cell gene expression data of 12 ISC
      markers were acquired from a total of 1215 cells. t-distributed stochastic
      neighbor embedding analysis identified clusters of candidate ISCs, and also
      revealed a distinct expression pattern of SMOC2 and LGR5 in ISC-cluster
      classified cells derived from aCD-SIOs. Single-cell organoid reformation assays
      showed significantly higher reformation efficiency by the cells of the aCD-SIOs
      compared with that of cells from NI-SIOs. CONCLUSIONS: aCD-SIOs harbor ISCs with
      modified marker expression profiles, and also with high organoid reformation
      ability. Results suggest modification of small intestinal stem cell properties by
      unidentified factors in the inflammatory environment of CD.

PMID- 29374778
TI  - Respiratory deficiency in yeast mevalonate kinase deficient may explain MKD
      associate metabolic disorder in humans.
AB  - Mevalonate kinase deficiency (MKD) an orphan drug rare disease affecting humans
      with different clinical presentations, is still lacking information about its
      pathogenesis; no animal or cell model mimicking the genetic defect, mutations at
      MVK gene, and its consequences on the mevalonate pathway is available. Trying to
      clarify the effects of MVK gene impairment on the mevalonate pathway we used a
      yeast model, the erg12-d mutant strain Saccharomyces cerevisiae (orthologous of
      MKV) retaining only 10% of mevalonate kinase (MK) activity, to describe the
      effects of reduced MK activity on the mevalonate pathway. Since shortage of
      isoprenoids has been described in MKD, we checked this observation using a
      physiologic approach: while normally growing on glucose, erg12-d showed growth
      deficiency in glycerol, a respirable carbon source, that was not rescued by
      supplementation with non-sterol isoprenoids, such as farnesol, geraniol nor
      geranylgeraniol, produced by the mevalonate pathway. Erg12-d whole genome
      expression analysis revealed specific downregulation of RSF2 gene encoding
      general transcription factor for respiratory genes, explaining the absence of
      growth on glycerol. Moreover, we observed the upregulation of genes involved in
      sulphur amino acids biosynthesis that coincided with the increasing in the amount
      of proteins containing sulfhydryl groups; upregulation of ubiquinone biosynthesis
      genes was also detected. Our findings demonstrated that the shortage of
      isoprenoids is not the main mechanism involved in the respiratory deficit and
      mitochondrial malfunctioning of MK-defective cells, while the scarcity of
      ubiquinone plays an important role, as already observed in MKD patients.

PMID- 29374780
TI  - Wound complications after ankle surgery. Does compression treatment work? A
      randomized, controlled trial.
AB  - PURPOSE: Infection rates following ankle fractures are as high as 19% in selected
      material and is the most common complication following this type of surgery, with
      potential catastrophic consequences. The purpose of this study was to test a
      regime of intermittent pneumatic compression, a compression bandage and a
      compression stocking and its effect on the rate of wound complications. The
      hypothesis was that compression could lower the infection rate from 20 to 5%.
      METHODS: We performed a randomized, controlled, non-blinded trial, including 153
      adult patients with unstable ankle fractures. Patients were randomized to either
      compression (N = 82) or elevation (N = 71). Patients with open fracture, DVT,
      pulmonary embolism, dementia, no pedal pulse, or no Danish address were excluded.
      Primary endpoint was infection. Secondary endpoints were necrosis and wound
      dehiscence. RESULTS: After 2 weeks, 1.4% (0.0;7.6) in the compression group had
      infection compared to 4.6% (1.0;12.9) in the control group, p = 0.35. The rate of
      necrosis after 2 weeks was 7.0% (95% CI 2.3;15.7) in the compression group
      compared with 26.2% (95% CI 16.0;38.5) in the elevation group, p = 0.004. No
      difference was shown regarding wound dehiscence. CONCLUSION: Based on this study,
      we cannot conclude if compression therapy prevents infection or not. This is
      mainly due to under-powering of the study. The effect on necrosis was in favor of
      compression, but the trial was not powered to show a difference regarding this
      endpoints and the result is thus hypothesis generating. Further research is
      needed before a thorough recommendation on the use of compression treatment that
      can be made.

PMID- 29374779
TI  - The Global Spine Care Initiative: a narrative review of psychological and social
      issues in back pain in low- and middle-income communities.
AB  - PURPOSE: The purpose of this review was to describe psychological and social
      factors associated with low back pain that could be applied in spine care
      programs in medically underserved areas and low- and middle-income countries.
      METHODS: We performed a narrative review of cohort, cross-sectional, qualitative
      and mixed methods studies investigating adults with low back pain using Medline
      and PubMed were searched from January 2000 to June 2015. Eligible studies had at
      least one of the following outcomes: psychological, social, psychosocial, or
      cultural/ethnicity factors. Studies met the following criteria: (1) English
      language, (2) published in peer-reviewed journal, (3) adults with spinal
      disorders, (4) included treatment, symptom management or prevention. RESULTS: Out
      of 58 studies, 29 were included in this review. There are few studies that have
      evaluated psychological and social factors associated with back pain in low- and
      middle-income communities, therefore, adapting recommendations from other regions
      may be needed until further studies can be achieved. CONCLUSION: Psychological
      and social factors are important components to addressing low back pain and
      health care providers play an important role in empowering patients to take
      control of their spinal health outcomes. Patients should be included in
      negotiating their spinal treatment and establishing treatment goals through
      careful listening, reassurance, and information providing by the health care
      provider. Instruments need to be developed for people with low literacy in
      medically underserved areas and low- and middle-income countries, especially
      where psychological and social factors may be difficult to detect and are poorly
      addressed. These slides can be retrieved under Electronic Supplementary Material.

PMID- 29374781
TI  - Evaluation of the clavicular tunnel placement on coracoclavicular ligament
      reconstruction for acromioclavicular dislocations: a finite element analysis.
AB  - PURPOSE: The two-tunnel coracoclavicular ligament reconstruction (CLR) technique
      is one of the treatment approaches commonly used in the surgical treatment of
      acromioclavicular (AC) injuries. Clavicular tunnel malposition is one of the
      major causes of failure in coracoclavicular ligament reconstruction. The main
      purpose of this study was to investigate the effects of clavicular tunnel
      placement on tendon loading in the CLR technique with finite element analysis.
      METHODS: Models of clavicle and scapula were constructed using computerized
      tomography images. Two clavicular bone tunnel reconstruction models were created
      with the tendon passing through the conoid and trapezoid tunnels. Four models
      based on the tunnel ratio (TR) method and defined as primary, anatomic,
      medialized, and lateralized were constructed to evaluate the effect of tunnel
      placement on loading conditions during tendon graft. All models were loaded by
      insertion from the trapezius and sternocleidomastoid muscles. The loading on the
      tendon were evaluated with the finite element analysis. RESULTS: The highest load
      value measured on the tendon was in the anatomic model (0.789 kPa), and the
      lowest load value (0.598 kPa) was measured in the lateralized tunnel model. The
      load value of the primary model was (0.657 kPa), and the medialized model's value
      was (0.752 kPa). CONCLUSIONS: In two-tunnel CLR technique, tendon loadings are
      related to tunnel placement. Medialized tunnel placement increases tendon
      loading. The TR method may be an appropriate option for determining tunnel
      placement.

PMID- 29374782
TI  - Epstein-Barr virus strain heterogeneity impairs human T-cell immunity.
AB  - The Epstein-Barr virus (EBV) establishes lifelong infections in > 90% of the
      human population. Although contained as asymptomatic infection by the immune
      system in most individuals, EBV is associated with the pathogenesis of
      approximately 1.5% of all cancers in humans. Some of these EBV-associated tumors
      have been successfully treated by the infusion of virus-specific T-cell lines.
      Recent sequence analyses of a large number of viral isolates suggested that
      distinct EBV strains have evolved in different parts of the world. Here, we
      assessed the impact of such sequence variations on EBV-specific T-cell immunity.
      With the exceptions of EBNA2 and the EBNA3 family of proteins, an overall low
      protein sequence disparity of about 1% was noted between Asian viral isolates,
      including the newly characterized M81 strain, and the prototypic EBV type 1 and
      type 2 strains. However, when T-cell epitopes including their flanking regions
      were compared, a substantial proportion was found to be polymorphic in different
      EBV strains. Importantly, CD4+ and CD8+ T-cell clones specific for viral epitopes
      from one strain often showed diminished recognition of the corresponding epitopes
      in other strains. In addition, T-cell recognition of a conserved epitope was
      affected by amino acid exchanges within the epitope flanking region. Moreover,
      the CD8+ T-cell response against polymorphic epitopes varied between donors and
      often ignored antigen variants. These results demonstrate that viral strain
      heterogeneity may impair antiviral T-cell immunity and suggest that
      immunotherapeutic approaches against EBV should preferably target broad sets of
      conserved epitopes including their flanking regions.

PMID- 29374783
TI  - Experimental infection in Cavia porcellus by infected Amblyomma ovale nymphs with
      Rickettsia sp. (Atlantic rainforest strain).
AB  - This study describes experimental infection of guinea pigs (Cavia porcellus)
      infested with naturally infected Amblyomma ovale nymphs with Rickettsia sp.
      (Atlantic rainforest strain), and the capacity of A. ovale nymphs to transmit
      this bacterium. Twenty-six guinea pigs were divided into the following groups:
      G1, 10 animals infested with uninfected A. ovale nymphs; G2, 10 animals infested
      with nymphs infected with Rickettsia sp. (Atlantic rainforest strain); and G3, 6
      animals without tick infestation. Blood samples were taken 7, 14, 21, and 28 days
      post-infestation for serological and hematological tests. For histopathological
      analysis and rickettsial DNA detection, fragments of the spleen, lung, brain, and
      liver were harvested after euthanasia. The average feeding period for nymphs was
      6.6 days for G1 and 6 days for G2. Hemolymph and PCR assays, performed to detect
      the causative agent in ticks, indicated that in G1, all ticks were negative, and
      in G2, all nymphs were positive by PCR and 80% (8/10) was positive by hemolymph
      tests. The only clinical change was skin scarring at the tick attachment site.
      Hematological parameters indicated leukopenia and total plasma protein (TPP)
      increased with decreased platelets in G1. In G2, leukocytosis, neutrophilia,
      monocytosis, an increase in platelets, and reduced TPP were observed. Only G2
      guinea pigs were seroconverted (80%; 8/10). Histopathology tests indicated mild,
      diffuse hemosiderosis and mild, multifocal, follicular hyperplasia in the spleen.
      Molecular analysis did not detect Rickettsia sp. DNA in C. porcellus tissues. We
      demonstrated the capacity of A. ovale nymphs to transmit Rickettsia sp. (Atlantic
      rainforest strain) to guinea pigs.

PMID- 29374785
TI  - Physical interventions for patients suffering from chemotherapy-induced
      polyneuropathy.

PMID- 29374784
TI  - Novel Henneguya spp. (Cnidaria: Myxozoa) from cichlid fish in the Amazon basin
      cluster by geographic origin.
AB  - We describe three new Henneguya spp. (Myxobolidae) found parasitizing two species
      of cichlid fish from the Amazon basin, Brazil: H. tucunarei n. sp. from gill
      filaments of Cichla monoculus and H. tapajoensis n. sp. from gill filaments of
      Cichla pinima, both from the Tapajos River, Para State and H. jariensis n. sp. in
      the fins of Cichla monoculus from the Jari River, Amapa State. We based
      descriptions on myxospore morphology and small subunit ribosomal DNA sequences,
      and used a phylogenetic analysis to compare the new Henneguya species with known
      relatives. Spores of the three species had similar morphology and morphometrics,
      but differed molecularly 5-7.5%, and were no more than 94% similar to any other
      sequence in GenBank. Together with having different hosts, these data supported
      the diagnosis of the parasites as distinct, novel species. Maximum likelihood and
      Bayesian analyses showed that H. tucunarei n. sp., H. tapajoensis n. sp., and H.
      jariensis n. sp. plus Henneguya paraensis (which parasitizes Cichla temensis)
      formed a well-supported sub-clade of Henneguya parasites of cichlids from the
      Amazon basin, in a lineage sister to those in characiforms hosts. Our analysis
      was consistent with previous studies that suggest that aquatic environment and
      vertebrate host group are the strongest correlates with phylogenetic signals in
      the Myxobolidae.

PMID- 29374786
TI  - Metal-free salan-type compound induces apoptosis and overcomes multidrug
      resistance in leukemic and lymphoma cells in vitro.
AB  - PURPOSE: We report on our preclinical findings of a simple salicylic diamine
      compound (THG 1213) which has yielded exceptional results as a potential
      chemotherapeutic drug. THG 1213 is an easy to synthesize chiral and metal-free
      salan compound. METHODS: THG 1213 was tested on several leukemia, lymphoma and
      solid tumor cell lines in vitro. The effects have been studied by LDH release
      essay, FACS flow cytometry, photometric cell count, immunoblotting, and NMR
      spectroscopy. RESULTS: THG 1213 selectively inhibits proliferation and induces
      apoptosis in leukemia, lymphoma and solid tumor cell lines. Necrosis or effects
      on healthy leucocytes could not be detected. Apoptosis is induced via the
      intrinsic and extrinsic pathways. The salan THG 1213 overcomes multidrug
      resistance in tumor cells and acts synergistically with vincristine and
      daunorubicin. CONCLUSIONS: THG 1213 displays remarkable antitumor properties. In
      particular, the lack of metallic components of THG 1213 could prove to be
      beneficial in future clinical trials, as metal-containing drugs are known to show
      severe side effects.

PMID- 29374787
TI  - Rab27a facilitates human parainfluenza virus type 2 growth by promoting cell
      surface transport of envelope proteins.
AB  - Human parainfluenza virus type 2 (hPIV-2) proteins and genomes newly synthesized
      in the cytoplasm need to be transported to the plasma membrane where budding
      occurs. This mechanism, where Rab proteins regulate intracellular traffic by
      switching between GTP-bound active form and GDP-bound inactive form, is not fully
      understood. mRNA and protein expression levels of Rab8a, Rab11a, and Rab27a are
      not altered by hPIV-2 infection. hPIV-2 growth is affected by depletion of Rab27a
      but not Rab8a and Rab11a. Overexpression of a constitutively active mutant of
      Rab27a Q78L promotes the cell surface levels of fusion (F) and hemagglutinin
      neuraminidase (HN) proteins in hPIV-2-infected cells without affecting viral mRNA
      levels. Increase in the cell surface level of F and HN proteins by Rab27a Q78L is
      noticeable when these proteins are coexpressed independent of hPIV-2 infection.
      Our results collectively suggest that the active form of Rab27a enhances hPIV-2
      growth by promoting transport of F and HN proteins to the plasma membrane.

PMID- 29374789
TI  - Mixture regression models for the gap time distributions and illness-death
      processes.
AB  - The aim of this study is to provide an analysis of gap event times under the
      illness-death model, where some subjects experience "illness" before "death" and
      others experience only "death." Which event is more likely to occur first and how
      the duration of the "illness" influences the "death" event are of interest.
      Because the occurrence of the second event is subject to dependent censoring, it
      can lead to bias in the estimation of model parameters. In this work, we
      generalize the semiparametric mixture models for competing risks data to
      accommodate the subsequent event and use a copula function to model the dependent
      structure between the successive events. Under the proposed method, the survival
      function of the censoring time does not need to be estimated when developing the
      inference procedure. We incorporate the cause-specific hazard functions with the
      counting process approach and derive a consistent estimation using the
      nonparametric maximum likelihood method. Simulations are conducted to demonstrate
      the performance of the proposed analysis, and its application in a clinical study
      on chronic myeloid leukemia is reported to illustrate its utility.

PMID- 29374788
TI  - Intraspecific and intraorganismal copy number dynamics of retrotransposons and
      tandem repeat in Aegilops speltoides Tausch (Poaceae, Triticeae).
AB  - Transposable elements (TE) and tandem repeats (TR) compose the largest fraction
      of the plant genome. The abundance and repatterning of repetitive DNA underlie
      intrapopulation polymorphisms and intraspecific diversification; however, the
      dynamics of repetitive elements in ontogenesis is not fully understood. Here, we
      addressed the genotype-specific and tissue-specific abundances and dynamics of
      the Ty1-copia, Ty3-gypsy, and LINE retrotransposons and species-specific Spelt1
      tandem repeat in wild diploid goatgrass, Aegilops speltoides Tausch. Copy numbers
      of TEs and TR were estimated by real-time quantitative PCR in vegetative and
      generative tissues in original plants from contrasting allopatric populations and
      artificial intraspecific hybrids. The results showed that between leaves and
      somatic spike tissues as well as in progressive microsporogenesis of individual
      genotypes, the copy numbers of three TEs correlatively oscillated between 2- to 4
      fold and the TR copy numbers fluctuated by 18- to 440-fold. Inter-individual and
      intraorganismal TEs and TR copy number dynamics demonstrate large-scale
      parallelism with extensive chromosomal rearrangements that were detected using
      fluorescent in situ hybridization in parental and hybrid genotypes. The data
      obtained indicate that tissue-specific differences in the abundance and pattern
      of repetitive sequences emerge during cell proliferation and differentiation in
      ontogenesis and reflect the reorganization of individual genomes in changing
      environments, especially in small peripheral population(s) under the influence of
      rapid climatic changes.

PMID- 29374790
TI  - Unilateral or bilateral laparoscopic ovarian drilling in polycystic ovary
      syndrome: a meta-analysis of randomized trials.
AB  - PURPOSE: This systematic review and meta-analysis aimed to compare the
      effectiveness of unilateral vs. bilateral laparoscopic ovarian drilling (ULOD vs.
      BLOD) for improving fertility outcomes in infertile women with clomiphene
      resistant polycystic ovary syndrome (PCOS) as well as its effect on ovarian
      reserve. METHODS: Searches were conducted on PubMed, ScienceDirect,
      ClinicalTrials.gov, and CENTRAL databases from January 1984 to January 2017. Only
      randomized trials comparing ULOD with BLOD were included. The PRISMA Statement
      was followed. Main outcomes were ovulation and clinical pregnancy rates per woman
      randomized. Secondary outcomes were; live birth and miscarriage rates as well as
      postoperative serum anti-mullerian hormone (AMH) concentration and antral
      follicle count (AFC). Quality assessment was performed by the Cochrane
      Collaboration risk of bias tool. RESULTS: Eight eligible trials (484 women) were
      analyzed. No significant difference was found in rates of ovulation (OR 0.73; 95%
      CI 0.47-1.11), clinical pregnancy (OR 0.56; 95% CI 0.22-1.41), live birth (OR
      0.77; 95% CI 0.28-2.10), or miscarriage (OR 0.90; 95% CI 0.33-2.84) when ULOD was
      compared with BLOD. The reduction in AMH was comparable between the two
      procedures (MD 0.64 ng/ml; 95% CI - 0.08 to 1.36). A significantly higher AFC at
      6-month follow-up was found with dose-adjusted ULOD (MD 2.20; 95% CI 1.01-3.39).
      CONCLUSIONS: After carefully weighing up the well-known benefits of BLOD against
      a potential risk to ovarian reserve, clinicians could be advised to offer the
      fixed-dose ULOD to their infertile patients with clomiphene-resistant PCOS. This
      is concordant with the "primum non nocere" principal if LOD will be envisaged.

PMID- 29374792
TI  - Association of grey matter changes with stability and flexibility of prediction
      in akinetic-rigid Parkinson's disease.
AB  - Parkinson's disease (PD), which is caused by degeneration of dopaminergic neurons
      in the midbrain, results in a heterogeneous clinical picture including cognitive
      decline. Since the phasic signal of dopamine neurons is proposed to guide
      learning by signifying mismatches between subjects' expectations and external
      events, we here investigated whether akinetic-rigid PD patients without mild
      cognitive impairment exhibit difficulties in dealing with either relevant
      (requiring flexibility) or irrelevant (requiring stability) prediction errors.
      Following our previous study on flexibility and stability in prediction (Trempler
      et al. J Cogn Neurosci 29(2):298-309, 2017), we then assessed whether deficits
      would correspond with specific structural alterations in dopaminergic regions as
      well as in inferior frontal cortex, medial prefrontal cortex, and the
      hippocampus. Twenty-one healthy controls and twenty-one akinetic-rigid PD
      patients on and off medication performed a task which required to serially
      predict upcoming items. Switches between predictable sequences had to be
      indicated via button press, whereas sequence omissions had to be ignored.
      Independent of the disease, midbrain volume was related to a general response
      bias to unexpected events, whereas right putamen volume correlated with the
      ability to discriminate between relevant and irrelevant prediction errors.
      However, patients compared with healthy participants showed deficits in
      stabilisation against irrelevant prediction errors, associated with thickness of
      right inferior frontal gyrus and left medial prefrontal cortex. Flexible updating
      due to relevant prediction errors was also affected in patients compared with
      controls and associated with right hippocampus volume. Dopaminergic medication
      influenced behavioural performance across, but not within the patients. Our
      exploratory study warrants further research on deficient prediction error
      processing and its structural correlates as a core of cognitive symptoms
      occurring already in early stages of the disease.

PMID- 29374793
TI  - Taurine supplementation prevents endothelial dysfunction and attenuates
      structural changes in aortas from hypothalamic obese rats.
AB  - PURPOSE: Obesity predisposes to cardiovascular and metabolic diseases. The amino
      acid, L-taurine (Tau), regulates glucose and lipid homeostasis and vascular
      function. Here we investigated whether Tau supplementation prevents endothelial
      dysfunction in the thoracic aortas of monosodium glutamate-induced obese (MSG)
      rats. METHODS: Male rats received subcutaneous injections of MSG (4 mg/kg body
      weight/day) or saline (control group, CTL) during the first five days of life.
      From 21 to 150 days of age, the rats were distributed into the groups: CTL, MSG,
      and CTL and MSG supplemented with 2.5% Tau in their drinking water (CTAU and
      MTAU). RESULTS: At 150-days old, MSG rats presented massive abdominal fat
      deposition, hypertriglyceridemia, hyperinsulinemia, glucose intolerance and high
      plasma levels of malondialdehyde (MDA), a lipid peroxidation marker. Tau
      supplementation attenuated fat accumulation in perigonadal adipose tissue and
      prevented the increase in triglycerides and MDA plasma levels. Aortic rings of
      MSG rats presented reduced vasodilation in response to acetylcholine (ACh). No
      modifications in insulin-induced vasodilatation, or Akt and eNOS phosphorylation,
      were observed in MSG aortas; thoracic aortas from MSG rats presented reduced
      tunica media thickness, with a lower aortic wall thickness/lumen diameter ratio
      and decreased total collagen content. Tau supplementation restored ACh-induced
      vasodilation and collagen content. CONCLUSIONS: Our study presents the first
      evidence that Tau prevents disruptions in vascular reactivity and in
      extracellular matrix composition in thoracic aortas of MSG-obese rats. The
      vascular protective actions of Tau may be linked to reduced lipid peroxidation
      and a reduction in cardiovascular risk factors, such as abdominal fat and
      hypertriglyceridemia.

PMID- 29374791
TI  - Recent Advances in Bronchopulmonary Dysplasia: Pathophysiology, Prevention, and
      Treatment.
AB  - Bronchopulmonary dysplasia (BPD) is potentially one of the most devastating
      conditions in premature infants with longstanding consequences involving multiple
      organ systems including adverse effects on pulmonary function and
      neurodevelopmental outcome. Here we review recent studies in the field to
      summarize the progress made in understanding in the pathophysiology, prognosis,
      prevention, and treatment of BPD in the last decade. The work reviewed includes
      the progress in understanding its pathobiology, genomic studies, ventilatory
      strategies, outcomes, and therapeutic interventions. We expect that this review
      will help guide clinicians to treat premature infants at risk for BPD better and
      lead researchers to initiate further studies in the field.

PMID- 29374794
TI  - The interaction between apolipoprotein B insertion/deletion polymorphism and
      macronutrient intake on lipid profile and serum leptin and ghrelin levels in type
      2 diabetes mellitus patients.
AB  - PURPOSE: We aimed to study whether macronutrient intake could modify the
      association between ApoB Ins/Del and lipid profile, and serum leptin and ghrelin
      in type 2 diabetes mellitus (T2DM) patients. METHODS: In this study, 700 T2DM
      patients were recruited. Anthropometric, biochemical and molecular data were
      collected, and Diet was assessed using a food frequency questionnaire. The
      interactions were tested using ANCOVA. RESULTS: Del-allele carriers with high
      MUFA and carbohydrate (>= 12 and >= 54% of energy, respectively) had
      significantly higher TG (P = 0.04) and LDL-C (P = 0.02) compared to Ins/Ins
      homozygotes, and these were not significant in subjects with low-MUFA and 
      carbohydrate (< 12 and < 54%, respectively). A significant interaction was
      observed between ApoB Ins/Del and diet on TG in both unadjusted (P = 0.03) and
      adjusted models (model 2 and 3, P = 0.04 and P = 0.04, respectively), and on LDL
      C only in adjusted models (model 2 and 3, P = 0.03 and P = 0.029, respectively).
      Besides, Del-allele carriers with protein, SFA, MUFA and n-3PUFA of >= 14, 9, 12
      and 0.6%, respectively, had a significant increase in their serum leptin than
      Ins/Ins homozygotes (P < 0.05). However, these associations were not significant
      between the two genetic groups in subjects with low intakes of protein, SFA, MUFA
      and n-3PUFA. Moreover, Del-allele carriers with low carbohydrate (< 54%) had
      significantly higher leptin and ghrelin than Ins/Ins homozygotes (P < 0.05),
      however, in high-carbohydrate group, leptin and ghrelin were not significantly
      lower. CONCLUSIONS: These findings indicate that the interaction between ApoB
      Ins/Del and dietary intake of MUFA, SFA, n-3PUFA, carbohydrate and protein could
      modulate the serum levels of TG, LDL-C, leptin and ghrelin in T2DM patients.

PMID- 29374795
TI  - Harvey Alan Lincoff, M.D. 1920-2017 a pioneer of ophthalmology.

PMID- 29374796
TI  - Subfoveal choroidal thickness predicts macular atrophy in age-related macular
      degeneration: results from the TREX-AMD trial.
AB  - BACKGROUND: Our purpose was to evaluate the relationship between subfoveal
      choroidal thickness (SCT) and development of macular atrophy (MA) in eyes with
      age-related macular degeneration (AMD). METHODS: This was a prospective,
      multicenter study. Sixty participants (120 eyes) in the TREX-AMD trial
      (NCT01648292) with treatment-naive neovascular AMD (NVAMD) in at least one eye
      were included. SCT was measured by certified reading center graders at baseline
      using spectral domain optical coherence tomography (SDOCT). The baseline SCT was
      correlated with the presence of MA at baseline and development of incident MA by
      month 18. Generalized estimating equations were used to account for information
      from both eyes. RESULTS: Baseline SCT in eyes with MA was statistically
      significantly less than in those without MA in both the dry AMD (DAMD) (P = 0.04)
      and NVAMD (P = 0.01) groups. Comparison of baseline SCT between MA developers and
      non-MA developers revealed a statistically significant difference (P = 0.03).
      Receiver operating characteristic curve (ROC) analysis showed the cut-off
      threshold of SCT for predicting the development of MA in cases without MA at
      baseline was 124 MUm (AUC = 0.772; Sensitivity = 0.923; Specificity = 0.5). Among
      eyes without MA at baseline, those with baseline SCT <=124 MUm were 4.3 times
      more likely to develop MA (Odds ratio: 4.3, 95% confidence interval: 1.6-12, P =
      0.005) than those with baseline SCT >124 MUm. CONCLUSIONS: Eyes with AMD and MA
      had less SCT than those without MA. Eyes with less baseline SCT also appear to be
      at higher risk to develop MA within 18 months.

PMID- 29374797
TI  - Effectiveness of School-Based Teen Pregnancy Prevention Programs in the USA: a
      Systematic Review and Meta-Analysis.
AB  - School-based programs have been a mainstay of youth pregnancy prevention efforts
      in the USA. We conducted a systematic review and meta-analysis to assess their
      effectiveness. Eligible studies evaluated the effect on pregnancy rates of
      programs delivered in elementary, middle, or high schools in the USA and Canada,
      published between January 1985 and September 2016. The primary outcome was
      pregnancy; secondary outcomes were delay in sexual initiation, condom use, and
      oral contraception use. Randomized controlled trials (RCTs) and non-RCTs with
      comparator groups were eligible. We developed a comprehensive search strategy,
      applied to major bibliographic databases, article bibliographies, gray
      literature, and contact with authors. We calculated risk ratios (RR) with 95%
      confidence intervals (CI) for each outcome and pooled data in random effects meta
      analysis. We used Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) to assess evidence quality. Ten RCTs and 11 non-RCTs conducted
      from 1984 to 2016 yielded 30 unique pooled comparisons for pregnancy, of which 24
      were not statistically significant. Six showed statistically significant changes
      in pregnancy rates: two with increased risk (RR 1.30, 95% CI 1.02-1.65; and RR
      1.39, 95% CI 1.10-1.75) and four with decreased risk ranging from RR 0.56, 95% CI
      0.41-0.77, to RR 0.75, 95% CI 0.58-0.96. All studies were at high risk of bias,
      and the quality of evidence was low or very low. Identified evidence indicated no
      consistent difference in rates of pregnancies between intervention recipients and
      controls.

PMID- 29374799
TI  - Application of CT perfusion to assess hemodynamics in symptomatic Moyamoya
      syndrome: focus on affected side and parameter characteristic.
AB  - OBJECTIVE: Vascular and hemodynamic changes were not consistent in symptomatic
      and non-symptomatic cerebral hemisphere in patients with symptomatic moyamoya
      syndrome (MMS). Thus, the purpose of this study is to evaluate the hemodynamic
      difference between symptomatic and non-symptomatic cerebral hemisphere in
      patients with symptomatic MMS. METHODS: Patients who were diagnosed with
      symptomatic MMS were retrospectively collected. All cases underwent CTP
      examination. Regions of interest (ROIs) were chosen in the mirroring bilateral
      frontal lobes, temporal lobes, the basal ganglia, and the brainstem as control
      region. The relative perfusion parameter values of symptomatic side were compared
      with non-symptomatic side. RESULTS: Of the 40 patients, 33 patients were taken
      into assessment. In all cases (n = 33), rCBF, rMTT, and rTTP in all regions of
      interest (ROIs) of the symptomatic side were significantly different from those
      of contralateral side. In unilateral MMS patients (n = 7), rCBF values were not
      significantly different between two sides in the temporal lobe and basal ganglia
      area; rTTP values were significantly higher in the symptomatic side. rMTT values
      were significantly higher only in the temporal lobe of symptomatic side. In
      bilateral MMS patients (n = 26), rCBF and rMTT in all ROIs of the symptomatic
      side were significantly different from those of contralateral side. However,
      there were no significant differences between two sides in all ROIs on rTTP
      values. CONCLUSIONS: This study demonstrates that rCBF and rMTT were more
      sensitive than rTTP for evaluating hemodynamic changes in patients with
      symptomatic bilateral MMS. Furthermore, patients with unilateral MMS may have a
      preserved rCBF compared to those with bilateral disease.

PMID- 29374798
TI  - Exophiala dermatitidis Endophthalmitis: Case Report and Literature Review.
AB  - We report a case of a 59-year-old male patient with a postoperative fungal
      infection of the left eye. A dark-pigmented yeast, Exophiala dermatitidis
      (previously known as Wangiella dermatitidis), was identified from the culture of
      the biopsy taken from the posterior capsule. The infection was successfully
      eradicated by a combination of surgical and medical (i.e., voriconazole and
      fluconazole) treatment. This is the first report of successfully treated E.
      dermatitidis endophthalmitis, which demonstrates that a prompt and aggressive
      antifungal therapy combined with surgical intervention is necessary to prevent
      vision loss in cases of endophthalmitis due to Exophiala species. Beside the case
      description, we also aim to provide a literature review of previously reported
      eye infections caused by Exophiala species in order to help the future diagnosis
      and management of the disease.

PMID- 29374800
TI  - Blood-based biomarkers predicting response to antidepressants.
AB  - Major depressive disorder is a common, serious and in some cases, life
      threatening condition and affects approximately 350 million people globally.
      Although there is effective treatment available for it, more than 50% of the
      patients fail to respond to the first antidepressant they receive. The selection
      of a distinct treatment is still exclusively based on clinical judgment without
      incorporating lab-derived objective measures. However, there is growing evidence
      of biomarkers that it helps to improve diagnostic processes and treatment
      algorithms. Here genetic markers and blood-based biomarkers of the monoamine
      pathways, inflammatory pathways and the hypothalamic-pituitary-adrenal (HPA) axis
      are reviewed. Promising findings arise from studies investigating inflammatory
      pathways and immune markers that may identify patients suitable for anti
      inflammatory based treatment regimes. Next, an early normalization of a disturbed
      HPA axis or depleted neurotrophic factors may predict stable treatment response.
      Genetic markers within the serotonergic system may identify patients who are
      vulnerable because of stressful life events, but evidence for guiding treatment
      regimes still is inconsistent. Therefore, there is still a great need for studies
      investigating and validating biomarkers for the prediction of treatment response
      to facilitate the treatment selection and shorten the time to remission and thus
      provide personalized medicine in psychiatry.

PMID- 29374801
TI  - Premature Coronary Heart Disease in South Asians: Burden and Determinants.
AB  - PURPOSE OF REVIEW: While the burden of cardiovascular disease (CVD) is on the
      decline globally, it is on the rise among South Asians. South Asians are also
      believed to present early with coronary artery disease (CAD) compared with other
      ethnicities. RECENT FINDINGS: South Asians have demonstrated a higher burden of
      premature CAD (PCAD) compared with other ethnicities. These findings are not
      limited to non-immigrant South Asians but have also been found in immigrant South
      Asians settled around the world. In this article, we first discuss studies
      evaluating PCAD among South Asians residing in South Asia and among South Asian
      immigrants in other countries. We then discuss several traditional risk factors
      that could explain PCAD in South Asians (diabetes, hypertension, dietary factors,
      obesity) and lipoprotein-associated risk (low HDL-C levels, higher triglycerides,
      and elevated apolipoprotein B levels). We then discuss several emerging areas of
      research among South Asians including the role of dysfunctional HDL, elevated
      lipoprotein(a), genetics, and epigenetics. Although various risk markers and risk
      factors of CAD have been identified in South Asians, how they impact therapy is
      not well-known. PCAD is prevalent in the South Asian population. Large-scale
      studies are needed to identify how this information can be rationally utilized
      for early identification of risk among South Asians, and how currently available
      therapies can mitigate this increased risk.

PMID- 29374802
TI  - Use of an ACE inhibitor or angiotensin receptor blocker is a major risk factor
      for dehydration requiring readmission in the setting of a new ileostomy.
AB  - PURPOSE: Diverting ileostomies help prevent major complications related to
      anastomoses after colorectal resection but can cause metabolic derangement and
      hypovolemia, leading to readmission. This paper aims to determine whether
      angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker
      (ARB) use increased the risk of readmission, or readmission specifically for
      dehydration after new ileostomy creation. METHODS: Retrospective analysis of
      patients undergoing diverting ileostomy at a tertiary-care hospital, 2009-2015.
      Primary outcome was 60-day readmission for dehydration; secondary outcomes
      included 60-day readmission for any cause, or for infection obstruction. RESULTS:
      Ninety-nine patients underwent diverting ileostomy creation, 59% with a primary
      diagnosis of colorectal cancer. The 60-day readmission rate was 36% (n = 36). Of
      readmitted patients, 39% (n = 14) were admitted for dehydration. Other
      readmission reasons were infection (33%) and obstruction (3%). The majority (64%,
      n = 9) of patients readmitted for dehydration were taking either an ACEi or an
      ARB. Compared to patients not readmitted for dehydration, those who were
      readmitted for dehydration were more likely to be on an ACEi or an ARB (11/85,
      13% vs. 9/14, 64%). After controlling for covariates, ACEi or ARB use was
      significantly associated with risk of readmission (p < 0.0001, odds ratio =
      13.56, 95% confidence interval 3.54-51.92,). No other diuretic agent was
      statistically associated with readmission for dehydration. CONCLUSIONS: ACEi and
      ARB use is a significant risk factor for readmission for dehydration following
      diverting ileostomy creation. Consideration should be given to withholding these
      medications after ileostomy creation to reduce this risk.

PMID- 29374803
TI  - Appropriateness of patients transferred with orthopedic injuries: experience of a
      level I trauma center.
AB  - BACKGROUND: Trauma patients are frequently transferred to a higher level of care
      for specialized orthopedic care. Many of these transfers are not necessary and
      waste valuable resources. The purpose of this study was to quantify our own
      experience and to assess the appropriateness of orthopedic transfers to a level I
      trauma center emergency department. METHODS: A retrospective review of orthopedic
      emergency department transfers to a level I trauma center was performed. Data
      collected included time of transfer, injury severity score (ISS), age, gender,
      race, orthopedic coverage at transfer institution, and insurance status. Two
      orthopedic trauma surgeons graded the appropriateness of transfer. A weighted
      logistic regression model was used to compare dependent and independent
      variables. RESULTS: A total of 324 patient transfers were reviewed; 65 (20.1%) of
      them were graded as inappropriate. There was no statistically significant
      relationship between appropriateness of transfer and age, availability of
      orthopedic coverage, night/weekend transfer, or insurance status. Regression
      analysis showed that only ISS (OR 1.130, p = .008) and "polytrauma" (OR 25.39, p
      < .0001) designation were associated with increased odds ratio of appropriate
      transfer. The kappa coefficient for inter-rater reliability between the two
      raters was 0.505 (95% CI, 0.388-0.623) reflecting moderate agreement. CONCLUSION:
      Inappropriate transfers create a significant medical burden to our health care
      system using valuable resources. Our study found similar results of inappropriate
      transfers compared to previous studies. However, we did not find a relationship
      between insurance status or nights/weekends and transfer appropriateness.

PMID- 29374804
TI  - Cultural and Religious Perspective on the Sufi Shrines.
AB  - This paper explains the Sufi shrines which hold great importance in Pakistani
      society. The Shrines inhabit a vital position in the cultural and social as well
      as religious and culture life of rituals, Saints, traditional belief, sounds,
      trance, dance, music in ethnic healing, and spiritual illness/disease. It is not
      only a place of belief and devotion based on Sufi shrines but a place where
      Muslims and non-Muslim take part in happiness activities together. The design and
      architecture of the Sufi Shrines have local as well as worldwide influences,
      representative spiritual, belief systems, economic, and esthetic dimensions of
      Muslim social institute. Therefore, Muslims' association with the Sufi Shrines
      has much importance from traditional, political, social and economic
      perspectives. Centered on an ethnographic illustration, this research aims to
      highlight the use of Sufi Shrines space and Peoples' Perceptions about Visiting
      Sufi shrines in the ethnic perspective of rural and urban Sindh. In addition to
      discuss the socio spatial interactions about the Sufi shrines, this study has
      discovered that majority of the people and visitors have strong belief systems
      upon the blessings of Sufis and they visit shrines to fulfill their social,
      economic, physical, mental and spiritual wishes.

PMID- 29374805
TI  - Approaching Spirituality Using the Patient-Centered Clinical Method.
AB  - Although the scientific literature already suggests the importance of spiritual
      care in clinical practice, this topic has been apart from the routine of many
      practitioners, and many physicians still have difficulties in how to carry out
      such approaches in the clinical setting. This article reflects on the importance
      of spirituality in the health-disease process and provides an approach to the
      biopsychosocial-spiritual care in the practice of primary care. In addition, the
      aim of the authors is to propose a spiritual approach based on the patient
      centered clinical method. This method has been used for clinical communication
      and can be powerful for exploring spiritual history. Thus, using a fictional case
      scenario as a practical example, the authors guide readers to understand the
      patient-centered approach they propose.

PMID- 29374806
TI  - Linking chloroplast relocation to different responses of photosynthesis to blue
      and red radiation in low and high light-acclimated leaves of Arabidopsis thaliana
      (L.).
AB  - Low light (LL) and high light (HL)-acclimated plants of A. thaliana were exposed
      to blue (BB) or red (RR) light or to a mixture of blue and red light (BR) of
      incrementally increasing intensities. The light response of photosystem II was
      measured by pulse amplitude-modulated chlorophyll fluorescence and that of
      photosystem I by near infrared difference spectroscopy. The LL but not HL leaves
      exhibited blue light-specific responses which were assigned to relocation of
      chloroplasts from the dark to the light-avoidance arrangement. Blue light (BB and
      BR) decreased the minimum fluorescence ([Formula: see text]) more than RR light.
      This extra reduction of the [Formula: see text] was stronger than theoretically
      predicted for [Formula: see text] quenching by energy dissipation but actual
      measurement and theory agreed in RR treatments. The extra [Formula: see text]
      reduction was assigned to decreased light absorption of chloroplasts in the
      avoidance position. A maximum reduction of 30% was calculated. Increasing
      intensities of blue light affected the fluorescence parameters NPQ and qP to a
      lesser degree than red light. After correcting for the optical effects of
      chloroplast relocation, the NPQ responded similarly to blue and red light. The
      same correction method diminished the color-specific variations in qP but did not
      abolish it; thus strongly indicating the presence of another blue light effect
      which also moderates excitation pressure in PSII but cannot be ascribed to
      absorption variations. Only after RR exposure, a post-illumination overshoot of
      [Formula: see text] and fast oxidation of PSI electron acceptors occurred, thus,
      suggesting an electron flow from stromal reductants to the plastoquinone pool.

PMID- 29374807
TI  - The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin
      Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond.
AB  - PURPOSE OF REVIEW: Sacubitril/valsartan (LCZ696) is a first-in-class, novel
      acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition
      of neprilysin and the angiotensin (AT1) receptor. A recent clinical trial
      PRARDIGM-HF demonstrated that this drug is superior to angiotensin-converting
      enzyme (ACE) inhibitors for improving the prognosis in the patients with heart
      failure, and this has resulted in the drug being included in clinical practice
      guidelines for the management of heart failure with reduced ejection fraction
      (EF). In addition, sacubitril/valsartan has been developed for the management of
      hypertension, because it has unique anti-aging properties. However, the clinical
      evidence of mechanism has not been well validated. RECENT FINDINGS: A recent
      mechanistic study PARAMETER demonstrated that sacubitril/valsartan (LCZ696) is
      superior to angiotensin receptor blocker (ARB) monotherapy for reducing central
      aortic systolic pressure (primary endpoint) as well as for central aortic pulse
      pressure (secondary endpoint) and nocturnal BP preferentially. Considering these
      results, sacubitril/valsartan may be an attractive therapeutic agent to treat the
      elderly with age-related hypertension phenotypes, such as drug-uncontrolled
      (resistant) hypertension characterized as systolic (central) hypertension
      (structural hypertension) and/or nocturnal hypertension (salt-sensitive
      hypertension). These are the high-risk hypertension phenotypes which are prone to
      develop heart failure with preserved EF and chronic kidney disease.
      Sacubitril/valsartan may be effective to suppress the age-related continuum from
      hypertension to heart failure, and it could be clinically useful not only for
      secondary prevention, but also as primary prevention of heart failure in
      uncontrolled elderly hypertensive patients.

PMID- 29374809
TI  - Final results of a phase I dose-escalation, dose-expansion study of adding
      disulfiram with or without copper to adjuvant temozolomide for newly diagnosed
      glioblastoma.
AB  - Disulfiram has shown promising activity including proteasome inhibitory
      properties and synergy with temozolomide in preclinical glioblastoma (GBM)
      models. In a phase I study for newly diagnosed GBM after chemoradiotherapy, we
      have previously reported our initial dose-escalation results combining disulfiram
      with adjuvant temozolomide and established the maximum tolerated dose (MTD) as
      500 mg per day. Here we report the final results of the phase I study including
      an additional dose-expansion cohort of disulfiram with concurrent copper. The
      phase I study consisted of an initial dose-escalation phase of disulfiram 500
      1000 mg daily during adjuvant temozolomide, followed by a dose-expansion phase of
      disulfiram 500 mg daily with copper 2 mg three times daily. Proteasome inhibition
      was assessed using fluorometric 20S proteasome assay on peripheral blood cell. A
      total of 18 patients were enrolled: 7 patients received 500 mg disulfiram, 5
      patients received 1000 mg disulfiram, and 6 patients received 500 mg disulfiram
      with copper. Two dose-limiting toxicities occurred with 1000 mg disulfiram. At
      disulfiram 500 mg with or without copper, only 1 patient (7%) required dose
      reduction during the first month of therapy. Addition of copper to disulfiram did
      not increase toxicity nor proteasome inhibition. The median progression-free
      survival was 4.5 months (95% CI 0.8-8.2). The median overall survival (OS) was
      14.0 months (95% CI 8.3-19.6), and the 2-year OS was 24%. The MTD of disulfiram
      at 500 mg daily in combination with adjuvant temozolomide was well tolerated by
      GBM patients, but 1000 mg daily was not. Toxicity and pharmacodynamic effect of
      disulfiram were similar with or without concurrent copper. The clinical efficacy
      appeared to be comparable to historical data. Additional clinical trials to
      combine disulfiram and copper with chemoradiotherapy or to resensitize recurrent
      GBM to temozolomide are ongoing.

PMID- 29374808
TI  - Pushing the Envelope: Laparoscopic Nephrectomy as Outpatient Surgery.
AB  - PURPOSE OF REVIEW: The purposes of this review were to identify the possible
      limiting factors prohibiting laparoscopic nephrectomy being performed as an
      outpatient surgery and optimize these limiting factors. RECENT FINDINGS:
      Laparoscopic nephrectomy for patients who have kidney cancer can be performed as
      an outpatient surgery in well-selected, well-educated, and well-informed patients
      in a well-prepared hospital culture. Patient confidence, pain, and hospital
      culture are the most important limiting factors to the performance of
      laparoscopic nephrectomy as an outpatient procedure. Controlling these factors
      leads to a high success rate for the outpatient procedure.

PMID- 29374810
TI  - Clinical and dosimetric study of radiotherapy for glioblastoma: three-dimensional
      conformal radiotherapy versus intensity-modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: We aimed to compare three-dimensional conformal
      radiotherapy (3D-CRT) with intensity-modulated radiotherapy (IMRT) for the
      treatment of glioblastoma. MATERIALS AND METHODS: Retrospective study of 220
      patients with glioblastoma, treated with 3D-CRT or IMRT, with or without surgery.
      Dosimetric parameters as well as clinical and survival data for the two
      techniques were analyzed and compared. RESULTS: The median conformity index was
      1.53 (range 0-2.69) for 3D-CRT and 1.25 (range 0.97-2.01) for IMRT, p < 10-4. The
      median homogeneity index was 0.10 (range 0.03-0.32) for 3D-CRT and 0.07 (range
      0.03-0.18) for IMRT, p < 10-4. There were significantly fewer acute grade 1 and 2
      neurological toxicities in the IMRT group especially for edema (1.3 versus 12.4%,
      p = 0.017), concentration disorders (6.6 versus 19.9%, p = 0.003) and
      consciousness disorders (2.6 versus 13.2%, p = 0.002) although IMRT patients had
      a significantly worse pre-treatment neurological status than 3D-CRT patients.
      Median survival was 16.0 months (range 11.9-17.8) for IMRT and 13.4 months (range
      11.7-15.7) for 3D-CRT patients (p = 0.542). CONCLUSION: IMRT improved target
      conformity and reduced neurological toxicities for patients with glioblastomas.

PMID- 29374811
TI  - A novel 3D-printed hybrid simulation model for robotic-assisted kidney
      transplantation (RAKT).
AB  - Robotic-assisted kidney transplantation (RAKT) offers key benefits for patients
      that have been demonstrated in several studies. A barrier to the wider uptake of
      RAKT is surgical skill acquisition. This is exacerbated by the challenges of
      modern surgery with reduced surgical training time, patient safety concerns and
      financial pressures. Simulation is a well-established method of developing
      surgical skill in a safe and controlled environment away from the patient. We
      have developed a 3D printed simulation model for the key step of the kidney
      transplant operation which is the vascular anastomosis. The model is anatomically
      accurate, based on the CT scans of patients and it incorporates deceased donor
      vascular tissue. Crucially, it was developed to be used in the robotic operating
      theatre with the operating robot to enhance its fidelity. It is portable and
      relatively inexpensive when compared with other forms of simulation such as
      virtual reality or animal lab training. It thus has the potential of being more
      accessible as a training tool for the safe acquisition of RAKT specific skills.
      We demonstrate this model here.

PMID- 29374813
TI  - Dynamic tissue perfusion assessment reflects associations between
      antihypertensive treatment and renal cortical perfusion in patients with chronic
      kidney disease and hypertension.
AB  - PURPOSE: Renal cortical perfusion measured in noninvasive, dynamic ultrasonic
      method is connected with the hemodynamic cardiac properties and renal function.
      Antihypertensive drugs affect the functioning of the heart and kidneys. The aim
      of the study was to evaluate the effect of a chronic use of antihypertensive
      drugs on ultrasound parameters of renal cortical perfusion. METHODS: The study
      included 56 consecutive patients (49 M + 7 F, age 54.0 +/- 13.3) with stable
      chronic kidney disease and hypertension. Color Doppler dynamic tissue perfusion
      measurement was used to assess renal cortical perfusion. RESULTS: Patients were
      treated with a mean of 2.7 +/- 1.4 antihypertensive drugs, of which diuretics
      accounted for 25%, angiotensin-converting enzyme inhibitors (ACE-I) together with
      angiotensin receptor blockers (ARB) 24%, beta-blockers (BB) 23%, calcium channel
      blockers 16%, alpha-1 blockers (alpha1B) 9% and centrally acting drugs 3%. All
      investigated groups of drugs correlated significantly with parameters of renal
      perfusion. In multivariable regression analyses adjusted to age, diuretics were
      connected with the decrease (r = - 0.473) and ACE-I + ARB (r = 0.390) with the
      improvement of proximal and whole renal cortex perfusion (R2 = 0.28; p < 0.001),
      whereas BB (r = - 0.372) and alpha1B (r = - 0.280) independently correlated with
      worsened perfusion of renal distal cortex (R2 = 0.21, p < 0.01). CONCLUSIONS: The
      type of antihypertensive therapy had a significant influence on the ultrasound
      parameters of renal cortical perfusion. Noninvasive, ultrasonic dynamic tissue
      perfusion measurement method appears to be an adequate tool to assess the impact
      of drugs on renal cortical perfusion.

PMID- 29374812
TI  - Differential recognition of natural and remodeled glycotopes by three Diocleae
      lectins.
AB  - The carbohydrate specificities of Dioclea grandiflora lectins DGL-I1 and DGL-II,
      and Galactia lindenii lectin II (GLL-II) were explored by use of remodeled
      glycoproteins as well as by the lectin hemagglutinating activity against
      erythrocytes from various species with different glycomic profiles. The three
      lectins exhibited differences in glycan binding specificity but also showed
      overlapping recognition of some glycotopes (i.e. Talpha glycotope for the three
      lectins; IIbeta glycotope for DGL-II and GLL-II lectins); in many cases the
      interaction with distinct glycotopes was influenced by the structural context,
      i.e., by the neighbouring sugar residues. Our data complement and expand the
      existing knowledge about the binding specificity of these three Diocleae lectins,
      and taken together with results of previous studies, allow us to suggest a
      functional map of the carbohydrate recognition which illustrate the impact of
      modification of basic glycotopes enhancing, permiting, or inhibiting their
      recognition by each lectin.

PMID- 29374815
TI  - Differences Between U.S.-Born and Non-U.S.-Born Black Adults Reported with
      Diagnosed HIV Infection: United States, 2008-2014.
AB  - Despite improvements in its treatment, HIV infection continues to affect Blacks
      disproportionally. Using National HIV Surveillance System data from 50 U.S.
      states and the District of Columbia, we examined demographic and epidemiologic
      differences between U.S.-born and non-U.S.-born Black adults. Of 110,452 Black
      adults reported with diagnosed HIV during 2008-2014 with complete country of
      birth information, 11.1% were non-U.S.-born. Non-U.S.-born were more likely to be
      older, female, have HIV infection attributed to heterosexual contact, have been
      diagnosed late, and live in the northeastern U.S. region. During 2014, the HIV
      diagnosis rate among African-born Black females was 1.4 times the rate of U.S.
      born Black males, 2 times the rate of African-born Black males, and 5.3 times the
      rate of U.S.-born Black females. We elucidate the differences between U.S.-born
      and non-U.S.-born Blacks on which to base culturally appropriate HIV-prevention
      programs and policies.

PMID- 29374814
TI  - Risk of renal stone formation in patients treated with luteinising hormone
      releasing hormone analogues for prostate cancer: importance of bone metabolism
      and urine calcium.
AB  - PURPOSE: To determine whether androgen blockade produces metabolic changes in
      urine and increases the risk of calculi after 1 year of treatment. MATERIALS AND
      METHODS: The study included 38 patients, from the period April 2015 to June 2016,
      diagnosed with locally advanced prostate cancer or lymph node metastasis, and
      with an indication of androgen blockade. Androgen blockade was started with
      luteinising hormone-releasing hormone (LHRH) analogues, and a blood specimen, a
      fasting urine and 24-h urine were collected at the time of inclusion, and then at
      1 year of follow-up. A study was performed at baseline and at 1 year with imaging
      tests. An analysis of the variables was performed with a p <= 0.05 considered as
      statistically significant. RESULTS: The mean age of the patients included in the
      study was 72.26 +/- 6.75 years. As regards the biochemistry parameters, an
      increase in osteocalcin (from 16.28 +/- 9.48 to 25.56 +/- 12.09 ng/ml; p = 0.001)
      and an increase in beta-crosslaps (from 0.419 +/- 0.177 to 0.743 +/- 0.268 ng/ml;
      p = 0.0001) were observed. In the urinary parameters, a significant increase was
      observed in the fasting calcium/creatinine ratio (from 0.08 +/- 0.06 to 0.13 +/-
      0.06; p = 0.002) and in the 24-h calcium renal excretion (from 117.69 +/- 66.92
      to 169.42 +/- 107.18 mg; p = 0.0001). Calculi formation was observed in 12 of the
      38 patients included (31.6%), with a mean size of 3.33 +/- 1.31 mm. CONCLUSION:
      Treatment with LHRH analogues, as well as increasing the appearance of metabolic
      syndrome and speeding up the loss bone mineral density, causes an increase in
      fasting urine calcium.

PMID- 29374816
TI  - A Time-Varying Connectivity Analysis from Distributed EEG Sources: A Simulation
      Study.
AB  - Time-varying connectivity analysis based on sources reconstructed using inverse
      modeling of electroencephalographic (EEG) data is important to understand the
      dynamic behaviour of the brain. We simulated cortical data from a visual spatial
      attention network with a time-varying connectivity structure, and then simulated
      the propagation to the scalp to obtain EEG data. Distributed EEG source modeling
      using sLORETA was applied. We compared different dipole (representing a source)
      selection strategies based on their time series in a region of interest. Next, we
      estimated multivariate autoregressive (MVAR) parameters using classical Kalman
      filter and general linear Kalman filter approaches followed by the calculation of
      partial directed coherence (PDC). MVAR parameters and PDC values for the selected
      sources were compared with the ground-truth. We found that the best strategy to
      extract the time series of a region of interest was to select a dipole with time
      series showing the highest correlation with the average time series in the region
      of interest. Dipole selection based on power or based on the largest singular
      value offer comparable alternatives. Among the different Kalman filter
      approaches, the use of a general linear Kalman filter was preferred to estimate
      PDC based connectivity except when only a small number of trials are available.
      In the latter case, the classical Kalman filter can be an alternative.

PMID- 29374817
TI  - Differential effects of sPLA2-GV and GX on cellular proliferation and lipid
      accumulation in HT29 colon cancer cells.
AB  - Secretory phospholipase A2 (sPLA2) group of enzymes have been shown to hydrolyze
      phospholipids, among which sPLA2 Group V (GV) and Group X (GX) exhibit high
      selectivity towards phosphatidylcholine-rich cellular plasma membranes. The
      enzymes have recently emerged as key regulators in lipid droplets formation and
      it is hypothesized that sPLA2-GV and GX enhanced cell proliferation and lipid
      droplet accumulation in colon cancer cells (HT29). In this study, cell viability
      and lipid droplet accumulation were assessed by Resazurin assay and Oil-Red-O
      staining. Interestingly, both sPLA2-GV and GX enzymes reduced intracellular lipid
      droplet accumulation and did not significantly affect cell proliferation in HT29
      cells. Incubation with varespladib, a pan-inhibitor of sPLA2-Group IIA/V/X,
      further suppressed lipid droplets accumulation in sPLA2-GV but have no effects in
      sPLA2-GX-treated cells. Further studies using catalytically inactive sPLA2
      enzymes showed that the enzymes intrinsic catalytic activity is required for the
      net reduction of lipid accumulation. Meanwhile, inhibition of intracellular
      phospholipases (iPLA2-gamma and cPLA2-alpha) unexpectedly enhanced lipid droplet
      accumulation in both sPLA2-GV and GX-treated cells. The findings suggested an
      interconnected relationship between extracellular and intracellular
      phospholipases in lipid cycling. Previous studies indicated that sPLA2 enzymes
      are linked to cancer development due to their ability to induce release of
      arachidonic acid and eicosanoids as well as the stimulation of lipid droplet
      formation. This study showed that the two enzymes work in a distinct manner and
      they neither confer proliferative advantage nor enhanced the net lipid droplet
      accumulation in HT29 cells.

PMID- 29374818
TI  - Long-Term Effectiveness of Laparoscopic Conversion of Sleeve Gastrectomy to a
      Biliopancreatic Diversion with a Duodenal Switch or a Roux-en-Y Gastric Bypass
      due to Weight Loss Failure.
AB  - BACKGROUND: Gastroesophageal reflux disease and inadequate weight loss (IWL) are
      long-term complications of laparoscopic sleeve gastrectomy (LSG) and indications
      for a laparoscopic conversion to an alternative bariatric procedure. The aim of
      this study is to report the long-term outcomes of biliopancreatic diversion with
      a duodenal switch (DS) or a Roux-en-Y gastric bypass (RYGB) as conversion
      procedures for weight loss failure after LSG. METHODS: The data of all patients
      who underwent post-LSG conversion to either a RYGB or a DS at our institution
      between November 2006 and May 2016 was retrospectively analyzed. Included were
      all patients with > 1-year follow-up who were operated due to IWL or weight
      regain. Patients with the indication of reflux were excluded. RESULTS: Sixty-six
      patients underwent conversion from LSG to RYGB, DS, or one-anastomosis gastric
      bypass during the study period. There were 21 revisions to DS and 18 to RYGB that
      met the inclusion criteria. The respective weight and body mass index (BMI)
      before and after LSG were 125 and 110 kg and 46 and 40.5 kg/m2 in the RYGB group
      and 148 and 126 kg and 53.7 and 46 kg/m2 in the DS group. At the last follow-up
      (> 2 years), 15 RYGB patients had a reduction in BMI of 8.5-31.9 kg/m2 and 18 DS
      patients had a reduction in BMI of 12.8-31.9 kg/m2. The mean follow-up was 48.5
      months (range 24-76). All comorbidities improved or underwent complete remission.
      CONCLUSION: Conversion from SG to RYGB or DS is an efficient and effective
      treatment for IWL and improvement of comorbidities. Further studies are warranted
      to evaluate long-term weight regain.

PMID- 29374819
TI  - A stress-free and grateful farewell.

PMID- 29374820
TI  - Paradigm shift in theranostics of neuroendocrine tumors: conceptual horizons of
      nanotechnology in nuclear medicine.
AB  - We present a comprehensive review of Neuroendocrine Tumors (NET) and the current
      and developing imaging and therapeutic modalities for NET with emphasis on
      Nuclear Medicine modalities. Subsequently, nanotechnology and its emerging role
      in cancer management, especially NET, are discussed. The article is both
      educative and informative. The objective is to provide an insight into the
      developments made in nuclear medicine and nanotechnology towards management of
      NET, individually as well as combined together.

PMID- 29374821
TI  - The Effect of Support and Training for Family Members on Access to Outpatient
      Services for Veterans with Posttraumatic Stress Disorder (PTSD).
AB  - The VA Program of Comprehensive Assistance for Family Caregivers (PCAFC) provides
      landmark support for family caregivers of post-9/11 veterans. This study examines
      PCAFC support for veterans with and without PTSD and assesses whether program
      effect differs by PTSD status using a pre-post, non-equivalent, propensity score
      weighted comparison group design (n = 24,280). Veterans with and without PTSD in
      PCAFC accessed more mental health, primary, and specialty care services than
      weighted comparisons. PCAFC participation had stronger effects on access to
      primary care for veterans with PTSD than for veterans without PTSD. For veterans
      with PTSD, PCAFC support might enhance health service use.

PMID- 29374822
TI  - Analysis of multi drug resistant tuberculosis (MDR-TB) financial protection
      policy: MDR-TB health insurance schemes, in Chhattisgarh state, India.
AB  - INTRODUCTION: There are significant financial barriers to access treatment for
      multi drug resistant tuberculosis (MDR-TB) in India. To address these challenges,
      Chhattisgarh state in India has established a MDR-TB financial protection policy
      by creating MDR-TB benefit packages as part of the universal health insurance
      scheme that the state has rolled out in their effort towards attaining Universal
      Health Coverage for all its residents. In these schemes the state purchases
      health insurance against set packages of services from third party health
      insurance agencies on behalf of all its residents. Provider payment reform by
      strategic purchasing through output based payments (lump sum fee is reimbursed as
      per the MDR-TB benefit package rates) to the providers - both public and private
      health facilities empanelled under the insurance scheme was the key intervention.
      AIM: To understand the implementation gap between policy and practice of the
      benefit packages with respect to equity in utilization of package claims by the
      poor patients in public and private sector. METHODS: Data from primary health
      insurance claims from January 2013 to December 2015, were analysed using an
      extension of 'Kingdon's multiple streams for policy implementation framework' to
      explain the implementation gap between policy and practice of the MDR-TB benefit
      packages. RESULTS: The total number of claims for MDR-TB benefit packages
      increased over the study period mainly from poor patients treated in public
      facilities, particularly for the pre-treatment evaluation and hospital stay
      packages. Variations and inequities in utilizing the packages were observed
      between poor and non-poor beneficiaries in public and private sector. Private
      providers participation in the new MDR-TB financial protection mechanism through
      the universal health insurance scheme was observed to be much lower than might be
      expected given their share of healthcare provision overall in India. CONCLUSION:
      Our findings suggest that there may be an implementation gap due to weak coupling
      between the problem and the policy streams, reflecting weak coordination between
      state nodal agency and the state TB department. There is a pressing need to build
      strong institutional capacity of the public and private sector for improving
      service delivery to MDR-TB patients through this new health insurance mechanism.

PMID- 29374823
TI  - Investigating peste des petits ruminants (PPR) in naturally infected goats and
      sheep in Anseba Region, Eritrea, by reverse transcription polymerase chain
      reaction (RT-PCR).
AB  - The impact of peste des petits ruminants (PPR) virus was investigated by reverse
      transcription polymerase chain reaction (RT-PCR) on different samples obtained
      from non-vaccinated diseased and necropsied sheep and goats showing PPR-like
      symptoms. The disease picture was typical and sheep were observed to be less
      susceptible. Nasal and rectal swabs, whole blood and pathological tissue samples
      from the lungs, intestine, and mesenteric lymph nodes were used for this study.
      The results of RT-PCR indicated that from a total of 32 samples collected, 12
      (41%) were positive by this method. Out of those collected samples, 29 were from
      goats and 3 were from sheep. Nasal and rectal swabs and blood samples were
      superior in detection of the PPR virus compared to other tissue samples.

PMID- 29374824
TI  - Central Nervous System Involvement in Peripheral T Cell Lymphoma.
AB  - PURPOSE OF REVIEW: Central nervous system (CNS) involvement in peripheral T cell
      lymphoma (PTCL) is a difficult condition to treat, both as a primary and a
      secondary disease. RECENT FINDINGS: Primary CNS lymphoma (PCNSL) in PTCL is very
      rare, making up only 2% of all PCNSLs. The incidence of CNS relapse is generally
      2-6% in all cases of PTCL, but the risk may vary by histologic subtype, and
      extranodal involvement > 1 has been consistently found to be a risk factor for
      CNS relapse. Currently, there is no consensus about indications for CNS
      prophylactic treatment. A high-dose systemic methotrexate-based regimen is the
      most commonly used treatment, with or without consolidation with high-dose
      chemotherapy with autologous stem cell transplantation for both primary and
      secondary CNS involvement. This approach, however, is generally toxic for older
      patients. New therapeutic approaches against PTCL are therefore needed.

PMID- 29374825
TI  - Optimizing Management of Heart Failure by Using Echo and Natriuretic Peptides in
      the Outpatient Unit.
AB  - Chronic heart failure (HF) is an important public health problem and is
      associated with high morbidity, high mortality, and considerable healthcare
      costs. More than 90% of hospitalizations due to worsening HF result from
      elevations of left ventricular (LV) filling pressures and fluid overload, which
      are often accompanied by the increased synthesis and secretion of natriuretic
      peptides (NPs). Furthermore, persistently abnormal LV filling pressures and a
      rise in NP circulating levels are well known indicators of poor prognosis.
      Frequent office visits with the resulting evaluation and management are most
      often needed. The growing pressure from hospital readmissions in HF patients is
      shifting the focus of interest from traditionally symptom-guided care to a more
      specific patient-centered follow-up care based on clinical findings, BNP and
      echo. Recent studies supported the value of serial NP measurements and Doppler
      echocardiographic biomarkers of elevated LV filling pressures as tools to
      scrutinize patients with impending clinically overt HF. Therefore, combination of
      echo and pulsed-wave blood-flow and tissue Doppler with NPs appears valuable in
      guiding ambulatory HF management, since they are potentially useful to
      distinguish stable patients from those at high risk of decompensation.

PMID- 29374826
TI  - Hematopoietic stem cell transplantation for acute myeloid leukemia.
AB  - Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields a
      high rate of curability for acute myeloid leukemia (AML), it is also associated
      with transplant-related morbidity and mortality (TRM). The risk and severity of
      TRM increase with the use of an alternative donor graft in the absence of an HLA
      matched sibling donor (MSD). With the declining birthrate and aging of the
      population, the numbers of patients with an MSD are decreasing, and alternative
      donor transplants, including the post-transplant cyclophosphamide method using
      haplo-identical donors, are increasing. Autologous (auto)-HSCT, which enables the
      intensification of chemotherapy, has the advantage of high availability of a
      transplant graft, and is associated with a lower TRM, but these benefits may be
      offset by a higher rate of relapse due to the lack of a graft-versus-leukemia
      (GVL) effect. Although allo-HSCT remains the first-line treatment for poor and
      very-poor-risk patients, auto-HSCT is again gaining increased attention. It has
      also recently been suggested that cord blood grafts may induce a stronger GVL
      effect than other grafts; as such, the positioning of cord blood transplantation
      should also be reconsidered for AML patients.

PMID- 29374827
TI  - Outcomes of strategic alternative donor selection or suspending donor search
      based on Japan Marrow Donor Program coordination status.
AB  - In allogeneic hematopoietic stem cell transplantation (allo-HSCT) from unrelated
      donors, delays in donor search are adversely associated with patient outcome.
      However, the optimal duration for either waiting for an unrelated donor or
      selecting alternative sources remains undetermined. Using data from the Japan
      Marrow Donor Program (JMDP) registry, we retrospectively analyzed 349 adult
      patients who had searched for unrelated donors. Two hundred and three patients
      received allo-HSCT from JMDP donors (Group A) with a median of 140 days required
      to identify a donor, 60 received allo-HSCT from alternative sources (Group B)
      after a median of 111.5 days at which point either all donor candidates had
      failed or the patient achieved a second or subsequent complete remission, and 77
      suspended allo-HSCT (Group C) after a median of 310 days. The 5-year overall
      survival (OS) rate in Group A was superior to that of Group C (48.6 vs 38.5%, P =
      0.001). Although Group B included more patients with high or very high disease
      risk index (DRI) at the time of allo-HSCT compared with Group A, the 5-year OS
      was not significantly different between Groups A and B (48.6 vs 40.9%, P = 0.07),
      indicating that switching to alternative donors may benefit patients with high
      DRI.

PMID- 29374828
TI  - The middle rectal artery arising from the lateral sacral artery.
AB  - A middle rectal artery arising from the lateral sacral artery (MRAls) in the
      right pelvis of a 99-year-old male was observed. Although variations of the
      origin of the middle rectal artery have been reported on many occasions, there
      are few descriptions of the trajectory in the literature. In our case, the MRAls
      branched from the lateral sacral artery on the sacral surface close to the third
      sacral sympathetic ganglion and immediately penetrated the third sacral
      splanchnic nerve and the parasympathetic pelvic splanchnic nerve from the ventral
      ramus of the forth sacral nerve. The MRAls entered in the lateral wall of the
      rectal ampulla without giving off a prostatic branch. Preservation of the pelvic
      autonomic nerves are crucial in rectal cancer excision to preserve the autonomic
      functions. The close topography of the MRAls to the origin of the fine autonomic
      nerves should be noted.

PMID- 29374829
TI  - In Vitro Safety Pharmacology Profiling of Topical alpha-Adrenergic Agonist
      Treatments for Erythema of Rosacea.
AB  - BACKGROUND: Topical alpha-adrenergic agonist therapy has been developed to treat
      the persistent erythema of rosacea patients. Brimonidine and oxymetazoline are
      both topical alpha-adrenergic agonists. OBJECTIVES: The objective of this in
      vitro safety pharmacology study was to compare the potential safety profiles of
      brimonidine and oxymetazoline. METHODS: Brimonidine and oxymetazoline underwent
      pharmacological profiling with a standard panel of 151 assays, including alpha
      adrenergic receptors and 5-hydroxytryptamine (5-HT) receptors. A valvular
      interstitial cell (VIC) proliferation assay was performed with oxymetazoline
      hydrochloride. RESULTS: Brimonidine was highly selective for the alpha2
      adrenergic receptors, specifically alpha2A, whereas oxymetazoline was found to be
      much less selective and was highly active against a wide range of targets.
      Negligible activity was observed with brimonidine at the 5-HT2B receptor, whereas
      oxymetazoline had significant 5-HT2B receptor agonist activity and caused
      proliferation of mitral VICs in vitro. CONCLUSION: As the 5-HT2B receptor is
      potentially involved in drug-induced valvulopathy, the benefit/risk ratio should
      be carefully considered, especially in patients with cardiovascular disease or
      other comorbidities.

PMID- 29374830
TI  - Correlations between near-infrared spectroscopy, perfusion index, and cardiac
      outputs in extremely preterm infants in the first 72 h of life.
AB  - : Haemodynamic assessment during the transitional period in preterm infants is
      challenging. We aimed to describe the relationships between cerebral regional
      tissue oxygen saturation (CrSO2), perfusion index (PI), echocardiographic, and
      clinical parameters in extremely preterm infants in their first 72 h of life.
      Twenty newborns born at < 28 weeks of gestation were continuously monitored with
      CrSO2 and preductal PI. Cardiac output was measured at H6, H24, H48, and H72. The
      median gestational age and birth weight were 25.0 weeks (24-26) and 750 g (655
      920), respectively. CrSO2 and preductal PI had r values < 0.35 with blood gases,
      lactates, haemoglobin, and mean blood pressure. Cardiac output significantly
      increased over the 72 h of the study period. Fifteen patients had at least one
      episode of low left and/or right ventricular output (RVO), during which there was
      a strong correlation between CrSO2 and superior vena cava (SVC) flow (at H6 (r =
      0.74) and H24 (r = 0.86)) and between PI and RVO (at H6 (r = 0.68) and H24 (r =
      0.92)). Five patients had low SVC flow (<= 40 mL/kg/min) at H6, during which PI
      was strongly correlated with RVO (r = 0.98). CONCLUSION: CrSO2 and preductal PI
      are strongly correlated with cardiac output during low cardiac output states.
      What is Known: * Perfusion index and near-infrared spectroscopy are non-invasive
      tools to evaluate haemodynamics in preterm infants. * Pre- and postductal
      perfusion indexes strongly correlate with left ventricular output in term
      infants, and near-infrared spectroscopy has been validated to assess cerebral
      oxygenation in term and preterm infants. What is New: * Cerebral regional tissue
      oxygen saturation and preductal perfusion index were strongly correlated with
      cardiac output during low cardiac output states. * The strength of the
      correlation between cerebral regional tissue oxygen saturation, preductal
      perfusion index, and cardiac output varied in the first 72 h of life, reflecting
      the complexity of the transitional physiology.

PMID- 29374833
TI  - Bioanalytical Methods for New Psychoactive Substances.
AB  - Bioanalysis of new psychoactive substances (NPS) is very challenging due to the
      growing number of compounds with new chemical structures found on the drugs of
      abuse market. Screening, identification, and quantification in biosamples are
      needed in clinical and forensic toxicology settings, and these procedures are
      more challenging than the analysis of seized drug material because of extremely
      low concentrations encountered in biofluids but also due to diverse metabolic
      alterations of the parent compounds. This article focuses on bioanalytical single
      and multi-analyte procedures applicable to a broad variety of NPS in various
      biomatrices, such as blood, urine, oral fluid, or hair. Sample preparation,
      instrumentation, detection modes, and data evaluation are discussed as well as
      corresponding pitfalls. PubMed-listed and English-written original research
      papers and review articles published online between 01 October 2012 and 30
      September 2017 were considered.

PMID- 29374834
TI  - Advancing Pharmacotherapy Development from Preclinical Animal Studies.
AB  - Animal models provide rapid, inexpensive assessments of an investigational drug's
      therapeutic potential. Ideally, they support the plausibility of therapeutic
      efficacy and provide a rationale for further investigation. Here, I discuss how
      the absence of clear effective-ineffective categories for alcohol use disorder
      (AUD) medications and biases in the clinical and preclinical literature affect
      the development of predictive preclinical alcohol dependence (AD) models.
      Invoking the analogical argument concept from the philosophy of science field, I
      discuss how models of excessive alcohol drinking support the plausibility of
      clinical pharmacotherapy effects. Even though these models are not likely be
      completely discriminative, they are sensitive to clinically effective medications
      and have revealed dozens of novel medication targets. In that context, I discuss
      recent preclinical work on GLP-1 receptor agonists, phosphodiesterase inhibitors,
      glucocorticoid receptor antagonists, nociception agonists and antagonists, and
      CRF1 antagonists. Clinically approved medications are available for each of these
      drug classes. I conclude by advocating a translational approach in which drugs
      are evaluated highly congruent preclinical models and human laboratory studies.
      Once translation is established, I suggest the burden is to develop hypothesis
      based therapeutic interventions maximizing the impact of the confirmed
      pharmacotherapeutic effects in the context of additional variables falling
      outside the model.

PMID- 29374831
TI  - Use of procalcitonin in the diagnosis of tuberculosis in infants and preschool
      children.
AB  - : Normal procalcitonin (PCT) levels have been reported in adult pulmonary
      tuberculosis (TB) but have not been previously investigated in children. We aimed
      to assess PCT levels at diagnosis of TB in young children in a low-burden
      setting. In a cross-sectional observational study in a referral pediatric center
      in Barcelona (Spain), we assessed the value of PCT and other inflammatory markers
      (leucocyte counts, C-reactive protein, and erythrocyte sedimentation rate) in the
      diagnosis of TB in pre-school children (< 6 years at diagnosis, n = 45), as
      compared with two control groups (pneumococcal pneumonia, n = 25; and healthy
      controls, n = 49). Normal PCT levels were observed at diagnosis of TB in most
      cases, while C-reactive protein values and leucocyte counts were slightly
      elevated when compared to healthy controls. All three inflammatory biomarkers
      were significantly higher in children with pneumococcal pneumonia. CONCLUSIONS:
      In our study, PCT was not a useful diagnostic test for TB in young children. In a
      low-burden TB setting, PCT may be of some value in distinguishing pulmonary TB
      from pneumococcal pneumonia. What is Known: * Diagnosis of pediatric tuberculosis
      on clinical evidence is difficult, particularly in infants and small children. *
      Studies in adults with tuberculosis have mostly reported normal procalcitonin
      levels at diagnosis. What is New: * In pre-scholars with tuberculosis,
      erythrocyte sedimentation rate and white blood cell counts were higher than in
      healthy controls, but procalcitonin was not. * Procalcitonin may be useful in the
      differential diagnosis of intrathoracic tuberculosis and pneumococcal pneumonia.

PMID- 29374832
TI  - Sport-based physical activity recommendations and modifications in C-reactive
      protein and arterial thickness.
AB  - : We analyzed the effects of 1 year of engagement in >= 300 min/week of organized
      sports on inflammatory levels and vascular structure in adolescents. The sample
      was composed of 89 adolescents (11.6 +/- 0.7 years old [43 boys and 46 girls]),
      stratified according to engagement in >= 300 min/week of sport practice during at
      least 12 months of follow-up (n = 15, sport practice; n = 74, non-sport
      practice). Arterial thickness (carotid and femoral) was assessed by ultrasound
      scan, while high sensitive C-reactive protein levels were used to assess
      inflammatory status. Trunk fatness (densitometry scanner), biological maturation
      (age at peak height velocity), blood pressure, and skipping breakfast were
      treated as covariates. Independently of body fatness and biological maturation,
      the group engaged in sports presented a higher reduction in C-reactive protein
      (mean difference -1.559 mg/L [95%CI -2.539 to -0.579]) than the non-sport group
      (mean difference -0.414 mg/L [95%CI -0.846 to 0.017]) (p = 0.040). There was a
      significant relationship between changes in C-reactive protein and changes in
      femoral intima-media thickness in the non-sport group (r = 0.311 [95%CI 0.026 to
      0.549]). CONCLUSION: Inflammation decreased in adolescents engaged in organized
      sports, independently of trunk fatness and biological maturation. Moreover,
      inflammation was related to arterial thickening only in adolescents not engaged
      in sports. What is Known: * Intima media thickness is a relevant marker of
      cardiovascular disease in pediatric groups, being affected by obesity and
      inflammation. * The importance of monitoring inflammatory markers from childhood
      is enhanced by the fact that alterations in these inflammatory markers in early
      life predict inflammation and alterations in carotid IMT in adulthood. What is
      New: * Anti-inflammatory properties related to physical exercise performed at
      moderate intensity, on inflammation and alterations in IMT are not clear in
      pediatric groups. * Due to the importance that sport participation has assumed as
      a promoter of improvements in health and quality of life, it is necessary to
      understand its potential benefits for cardiovascular health during human growth.

PMID- 29374835
TI  - The Role of Glia in Sleep Regulation and Function.
AB  - The cellular mechanisms governing the expression, regulation, and function of
      sleep are not entirely understood. The traditional view is that these mechanisms
      are neuronal. An alternative view is that glial brain cells may play important
      roles in these processes. Their ubiquity in the central nervous system makes them
      well positioned to modulate neuronal circuits that gate sleep and wake. Their
      ability to respond to chemical neuronal signals suggests that they form feedback
      loops with neurons that may globally regulate neuronal activity. Their potential
      role in detoxifying the brain, regulating neuronal metabolism, and promoting
      synaptic plasticity raises the intriguing possibility that glia mediate important
      functions ascribed to sleep.

PMID- 29374837
TI  - Hepatic Immune System: Adaptations to Alcohol.
AB  - Both the innate and adaptive immune systems are critical for the maintenance of
      healthy liver function. Immune activity maintains the tolerogenic capacity of the
      liver, modulates hepatocellular response to various stresses, and orchestrates
      appropriate cellular repair and turnover. However, in response to heavy, chronic
      alcohol exposure, the finely tuned balance of pro- and anti-inflammatory
      functions in the liver is disrupted, leading to a state of chronic inflammation
      in the liver. Over time, this non-resolving inflammatory response contributes to
      the progression of alcoholic liver disease (ALD). Here we review the
      contributions of the cellular components of the immune system to the progression
      of ALD, as well as the pathophysiological roles for soluble and circulating
      mediators of immunity, including cytokines, chemokines, complement, and
      extracellular vesicles, in ALD. Finally, we compare the role of the innate immune
      response in health and disease in the liver to our growing understanding of the
      role of neuroimmunity in the development and maintenance of a healthy central
      nervous system, as well as the progression of neuroinflammation.

PMID- 29374838
TI  - Translational Model Systems for Complex Sodium Channel Pathophysiology in Pain.
AB  - Chronic pain patients are often left with insufficient treatment as the
      pathophysiology especially of neuropathic pain remains enigmatic. Recently,
      genetic variations in the genes of the voltage-gated sodium channels (Navs) were
      linked to inherited neuropathic pain syndromes, opening a research pathway to
      foster our understanding of the pathophysiology of neuropathic pain. More than 10
      years ago, the rare, inherited pain syndrome erythromelalgia was linked to
      mutations in the subtype Nav1.7, and since then a plethora of mutations and
      genetic variations in this and other Nav genes were identified. Often the
      biophysical changes induced by the genetic alteration offer a straightforward
      explanation for the clinical symptoms, but mutations in some channels, especially
      Nav1.9, paint a more complex picture. Although efforts were undertaken to
      significantly advance our knowledge, translation from heterologous or animal
      model systems to humans remains a challenge. Here we present recent advances in
      translation using stem cell-derived human sensory neurons and their potential
      application for identification of better, effective, and more precise treatment
      for the individual pain patient.

PMID- 29374836
TI  - Corticotropin-Releasing Factor (CRF) Neurocircuitry and Neuropharmacology in
      Alcohol Drinking.
AB  - Alcohol use is pervasive in the United States. In the transition from
      nonhazardous drinking to hazardous drinking and alcohol use disorder,
      neuroadaptations occur within brain reward and brain stress systems. One brain
      signaling system that has received much attention in animal models of excessive
      alcohol drinking and alcohol dependence is corticotropin-releasing factor (CRF).
      The CRF system is composed of CRF, the urocortins, CRF-binding protein, and two
      receptors - CRF type 1 and CRF type 2. This review summarizes how acute, binge,
      and chronic alcohol dysregulates CRF signaling in hypothalamic and extra
      hypothalamic brain regions and how this dysregulation may contribute to changes
      in alcohol reinforcement, excessive alcohol consumption, symptoms of negative
      affect during withdrawal, and alcohol relapse. In addition, it summarizes
      clinical work examining CRF type 1 receptor antagonists in humans and discusses
      why the brain CRF system is still relevant in alcohol research.

PMID- 29374839
TI  - Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations
      and Drinking Behavior.
AB  - Neural mechanisms underlying alcohol use disorder remain elusive, and this lack
      of understanding has slowed the development of efficacious treatment strategies
      for reducing relapse rates and prolonging abstinence. While synaptic adaptations
      produced by chronic alcohol exposure have been extensively characterized in a
      variety of brain regions, changes in intrinsic excitability of critical
      projection neurons are understudied. Accumulating evidence suggests that
      prolonged alcohol drinking and alcohol dependence produce plasticity of intrinsic
      excitability as measured by changes in evoked action potential firing and after
      hyperpolarization amplitude. In this chapter, we describe functional changes in
      cell firing of projection neurons after long-term alcohol exposure that occur
      across species and in multiple brain regions. Adaptations in calcium-activated
      (KCa2), voltage-dependent (KV7), and G protein-coupled inwardly rectifying (Kir3
      or GIRK) potassium channels that regulate the evoked firing and after
      hyperpolarization parallel functional changes in intrinsic excitability induced
      by chronic alcohol. Moreover, there are strong genetic links between alcohol
      related behaviors and genes encoding KCa2, KV7, and GIRK channels, and
      pharmacologically targeting these channels reduces alcohol consumption and
      alcohol-related behaviors. Together, these studies demonstrate that chronic
      alcohol drinking produces adaptations in KCa2, KV7, and GIRK channels leading to
      impaired regulation of the after-hyperpolarization and aberrant cell firing.
      Correcting the deficit in the after-hyperpolarization with positive modulators of
      KCa2 and KV7 channels and altering the GIRK channel binding pocket to block the
      access of alcohol represent a potentially highly effective pharmacological
      approach that can restore changes in intrinsic excitability and reduce alcohol
      consumption in affected individuals.

PMID- 29374840
TI  - The inhibitory effect of sacral dorsal root ganglion stimulation on nociceptive
      and nonnociceptive bladder reflexes in cats.
AB  - PURPOSE: To investigate the inhibitory effects of electrical stimulation of
      sacral dorsal root ganglion (DRG) on bladder activity under non-nociceptive and
      nociceptive bladder conditions in cats. MATERIALS AND METHODS: 12 cats were
      divided into non-nociceptive and nociceptive groups. Saline was used to distend
      the bladder and induce non-nociceptive bladder activity, while acetic acid (AA,
      0.25%) was used to induce nociceptive bladder overactivity, S1 or S2 DRG
      stimulation was applied via a pair of hook electrodes placed in the right S1 and
      S2 DRG. RESULTS: In both non-nociceptive and nociceptive groups, stimulation at 3
      and 5 Hz significantly increased bladder capacity (BC) and no significantly
      different between the two frequencies. In non-nociceptive group, S1 DRG
      stimulation at 3 Hz was as effective (increasing BC to 139.7 +/- 5.6 and 166.9 +/
      12.21% of control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases
      BC to 129.2 +/- 5.6 and 160.5 +/- 13.3% of control). In nociceptive group, AA
      reduced the BC to 62.6 +/- 11.7% of saline control. S1 DRG stimulation at 3 Hz
      was also as effective (increasing BC to 54.9 +/- 5.5 and 61.9 +/- 6.0% of saline
      control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 58.3
      +/- 3.7 and 65.6 +/- 3.7% of control). CONCLUSION: This study showed the
      effective inhibition on bladder activity under both non-nociceptive and
      nociceptive conditions, suggesting the possibility of sacral DRG stimulation to
      treat bladder overactivity.

PMID- 29374841
TI  - Robot-assisted laparoscopic versus open ureteral reimplantation for pediatric
      vesicoureteral reflux: a systematic review and meta-analysis.
AB  - OBJECTIVE: To compare the efficacy and safety of robot-assisted laparoscopic
      ureteral reimplantation (RALUR) and open ureteral reimplantation (OUR) in
      treating primary pediatric vesicoureteral reflux (VUR) based on published
      literature. METHODS: A comprehensive literature search of PubMed, Embase,
      Cochrane Library, CBM, CNKI and VIP databases was conducted to identify studies
      comparing the outcomes of RALUR with OUR for treating primary pediatric VUR. The
      last search was in January 2017. Summarized mean differences (MDs) or odds ratios
      (ORs) with 95% confidence intervals (CIs) were used to assess the differences in
      outcomes between RALUR and OUR. RESULTS: A total of six studies containing 7122
      children with primary VUR were included in this analysis. Significantly longer
      operation time was needed for RALUR than OUR (MD 66.69 min, 95% CI 41.71-91.67, P
      < 0.00001), while the RALUR group had significantly fewer days of hospital stay
      (MD - 17.80 h, 95% CI - 21.18 to - 14.42, P < 0.00001) and postoperative Foley
      placement (MD - 0.32 days, 95% CI - 0.57 to - 0.07, P = 0.01). No significant
      differences were found in estimated blood loss during operation, success rate,
      complications, and postoperative analgesia usage between the two groups. In
      subgroup analyses, a significantly higher rate of short-term postoperative
      complications in RALUR was found compared with OUR (OR 3.17, 95% CI 1.72-5.85, P
      = 0.0002). CONCLUSIONS: Our study indicates that compared with OUR, RALUR is also
      an effective surgical approach for primary pediatric VUR and could help patients
      return to society more quickly; however, short-term postoperative complications
      of RALUR should be considered cautiously.

PMID- 29374842
TI  - High-power HoLEP: no thanks!

PMID- 29374843
TI  - Rearing system for the predatory phytoseiid Euseius concordis (Acari:
      Phytoseiidae).
AB  - Several species of predatory mites, especially those of the family Phytoseiidae,
      are potentially useful for the control of pest mites and insects. Among the
      phytoseiids, Euseius concordis (Chant), a species commonly found in South
      America, has been studied for possible use as biological control agent of pest
      mites. Given that Euseius species are known to feed on plant leaves and on
      pollen, the objective of this study was to determine plant species and pollen
      sources suitable to establish a pilot method of production of that species, based
      on a set of comparisons in the laboratory. Out of four plant species evaluated in
      the study, higher survivorship of E. concordis females in the absence of
      supplementary food was observed on leaflets of Canavalia ensiformis L. Out of two
      pollen types, higher survivorship was obtained on pollen of Typha domingensis L.
      In a subsequent step, the population of E. concordis increased 19.3* within 21
      days when that pollen of T. domingensis was offered to the predator on plantlets
      of C. ensiformis, at 25.0 +/- 1  degrees C, 70.0 +/- 10% RH and 12 h photophase.
      Future studies may confirm the economic viability of this setup for the mass
      production of E. concordis.

PMID- 29374844
TI  - First record of the tick Ixodes (Pholeoixodes) kaiseri in Turkey.
AB  - Nymphs and larvae belonging to Ixodes spp. were collected from a red fox in
      Turkey. The ticks were identified morphologically and molecularly (16S rDNA PCR
      and phylogenetic analysis) as I. kaiseri. Sequence and phylogenetic analyses show
      that our I. kaiseri isolate is very similar to I. kaiseri isolates collected from
      Germany, Serbia, Romania, and Hungary. Therefore, the existence of I. kaiseri has
      been demonstrated for the first time in Turkey. More studies relating to the
      regional distribution and vectorial competence of I. kaiseri are needed.

PMID- 29374846
TI  - Structural and functional papez circuit integrity in amyotrophic lateral
      sclerosis.
AB  - Cognitive impairment in amyotrophic lateral sclerosis (ALS) is heterogeneous but
      now recognized as a feature in non-demented patients and no longer exclusively
      attributed to executive dysfunction. However, despite common reports of temporal
      lobe changes and memory deficits in ALS, episodic memory has been less explored.
      In the current study, we examined how the Papez circuit-a circuit known to
      participate in memory processes-is structurally and functionally affected in ALS
      patients (n = 20) compared with healthy controls (n = 15), and whether these
      changes correlated with a commonly used clinical measure of episodic memory. Our
      multimodal MRI approach (cortical volume, voxel-based morphometry, diffusion
      tensor imaging and resting state functional magnetic resonance) showed reduced
      gray matter in left hippocampus, left entorhinal cortex and right posterior
      cingulate as well as increased white matter fractional anisotropy and decreased
      mean diffusivity in the left cingulum bundle (hippocampal part) of ALS patients
      compared with controls. Interestingly, thalamus, mammillary bodies and fornix
      were preserved. Finally, we report a decreased functional connectivity in ALS
      patients in bilateral hippocampus, bilateral anterior and posterior
      parahippocampal gyrus and posterior cingulate. The results revealed that ALS
      patients showed statistically significant structural changes, but more important,
      widespread prominent functional connectivity abnormalities across the regions
      comprising the Papez circuit. The decreased functional connectivity found in the
      Papez network may suggest these changes could be used to assess risk or assist
      early detection or development of memory symptoms in ALS patients even before
      structural changes are established.

PMID- 29374845
TI  - Evaluation of vaccine potential of 2-Cys peroxiredoxin from the hard tick
      Haemaphysalis longicornis.
AB  - Ticks require blood feeding on vertebrate animals throughout their life cycle,
      and also concentrate the iron-containing blood, resulting in a high concentration
      of hydrogen peroxide (H2O2). High concentrations of H2O2 are harmful to
      organisms, due to their serious damage of macromolecules. Ticks have antioxidant
      enzymes, such as peroxiredoxins (Prxs), that scavenge H2O2. Prxs may have
      important roles in regulating the H2O2 concentration in ticks during blood
      feeding and oviposition. Moreover, Prxs are considered potential vaccine
      candidates in other parasites, such as Leishmania and Fasciola. In the present
      study, the efficacy of a tick Prx (HlPrx2) as a vaccine candidate antigen was
      evaluated. First, recombinant HlPrx2 (rHlPrx2) was expressed in Escherichia coli,
      and then, its purity and endotoxin levels were confirmed prior to administration.
      The rHlPrx2 proteins were of high purity with acceptably low endotoxin levels.
      Second, the ability of rHlPrx2 administration to stimulate mouse immunity was
      evaluated. The rHlPrx2 protein, with or without an adjuvant, could stimulate
      immunity in mice, especially the IgG1 of Th2 immune response. Using Western blot
      analysis, we also observed whether rHlPrx2-immunized mice sera could recognize
      native HlPrx2 protein in crude tick midgut proteins. Western blot analysis
      demonstrated that rHlPrx2-administrated mouse sera could detect the native
      HlPrx2. Finally, the effects of rHlPrx2 immunization in mice were studied using
      nymphal ticks. Although the challenged ticks were not affected by rHlPrx2
      immunization, rHlPrx2 still might be considered as a vaccine candidate against
      ticks because of its high immunogenicity.

PMID- 29374847
TI  - Volumetric and reflective device dead space of anaesthetic reflectors under
      different conditions.
AB  - Inhalation sedation is increasingly performed in intensive care units. For this
      purpose, two anaesthetic reflectors, AnaConDaTM and MirusTM are commercially
      available. However, their internal volume (100 ml) and possible carbon dioxide
      reflection raised concerns. Therefore, we compared carbon dioxide elimination of
      both with a heat moisture exchanger (HME, 35 ml) in a test lung model. A constant
      flow of carbon dioxide was insufflated into the test lung, ventilated with 500
      ml, 10 breaths per minute. HME, MIRUS and AnaConDa were connected successively.
      Inspired (insp-CO2) and end-tidal carbon dioxide concentrations (et-CO2) were
      measured under four conditions: ambient temperature pressure (ATP), body
      temperature pressure saturated (BTPS), BTPS with 0.4 Vol% (ISO-0.4), and 1.2 Vol%
      isoflurane (ISO-1.2). Tidal volume increase to maintain normocapnia was also
      determined. Insp-CO2 was higher with AnaConDa compared to MIRUS and higher under
      ATP compared to BTPS. Isoflurane further decreased insp-CO2 and abolished the
      difference between AnaConDa and MIRUS. Et-CO2 showed similar effects. In addition
      to volumetric dead space, reflective dead space was determined as 198 +/- 6/58 +/
      6/35 +/- 0/25 +/- 0 ml under ATP/BTPS/ISO-0.4/ISO-1.2 conditions for AnaConDa,
      and 92 +/- 6/25 +/- 0/25 +/- 0/25 +/- 0 ml under the same conditions for MIRUS,
      respectively. Under BTPS conditions and with the use of moderate inhaled agent
      concentrations, reflective dead space is small and similar between the two
      devices.

PMID- 29374848
TI  - Honeybees (Apis mellifera) as a biological barrier for contamination of honey by
      environmental toxic metals.
AB  - The aim of the study was to investigate the transfer of toxic metals from
      honeybee workers (Apis mellifera L.) to bee honey in relation to the ecological
      state of the environment. The materials of the study consisted of samples of
      honeybee bodies and varietal honeys taken from the same apiary located in three
      areas: R1-urbanized (16), R2-ecologically clean (16) and R3-industrialized (15)
      of south-eastern Poland. The contents of 14 elements in all tested samples,
      including toxic metals (Cd, Pb, Hg, Al, Ni, Tl) as well as bioelements (K, Mg,
      Ca, Mn, Fe, Zn, Cu, Se), were analysed by the ICP-OES method with prior microwave
      mineralization. The concentrations of the majority of the studied elements,
      excluding aluminum and lead, were significantly higher in bee bodies than in
      honey samples (P < 0.05). The pollution of bee bodies by toxic metals was
      dependent on the environmental cleanliness, and the most pollution was observed
      in the industrialized area. The bee body was the most effective barrier for Cd
      and Tl transfer to the honey, while the level of Ni was similar in both tested
      materials. The Al concentration was significantly higher in honey than bee bodies
      (14.81 +/- 24.69 and 6.51 +/- 5.83 mg kg-1, respectively), which suggests the
      possibility of secondary contamination of honey. The greatest sensitivity to
      heavy metal pollution was observed in honeydew honey compared to nectar honeys (P
      < 0.05). It was proved for the first time that bees work as biofilters for toxic
      metals and prevent honey contamination.

PMID- 29374849
TI  - Zebrafish Embryonic Slow Muscle Is a Rapid System for Genetic Analysis of
      Sarcomere Organization by CRISPR/Cas9, but Not NgAgo.
AB  - Zebrafish embryonic slow muscle cells, with their superficial localization and
      clear sarcomere organization, provide a useful model system for genetic analysis
      of muscle cell differentiation and sarcomere assembly. To develop a quick assay
      for testing CRISPR-mediated gene editing in slow muscles of zebrafish embryos, we
      targeted a red fluorescence protein (RFP) reporter gene specifically expressed in
      slow muscles of myomesin-3-RFP (Myom3-RFP) zebrafish embryos. We demonstrated
      that microinjection of RFP-sgRNA with Cas9 protein or Cas9 mRNA resulted in a
      mosaic pattern in loss of RFP expression in slow muscle fibers of the injected
      zebrafish embryos. To uncover gene functions in sarcomere organization, we
      targeted two endogenous genes, slow myosin heavy chain-1 (smyhc1) and heat shock
      protein 90 alpha1 (hsp90alpha1), which are specifically expressed in zebrafish
      muscle cells. We demonstrated that injection of Cas9 protein or mRNA with
      respective sgRNAs targeted to smyhc1 or hsp90a1 resulted in a mosaic pattern of
      myosin thick filament disruption in slow myofibers of the injected zebrafish
      embryos. Moreover, Myom3-RFP expression and M-line localization were also
      abolished in these defective myofibers. Given that zebrafish embryonic slow
      muscles are a rapid in vivo system for testing genome editing and uncovering gene
      functions in muscle cell differentiation, we investigated whether microinjection
      of Natronobacterium gregoryi Argonaute (NgAgo) system could induce genetic
      mutations and muscle defects in zebrafish embryos. Single-strand guide DNAs
      targeted to RFP, Smyhc1, or Hsp90alpha1 were injected with NgAgo mRNA into Myom3
      RFP zebrafish embryos. Myom3-RFP expression was analyzed in the injected embryos.
      The results showed that, in contrast to the CRISPR/Cas9 system, injection of the
      NgAgo-gDNA system did not affect Myom3-RFP expression and sarcomere organization
      in myofibers of the injected embryos. Sequence analysis failed to detect genetic
      mutations at the target genes. Together, our studies demonstrate that zebrafish
      embryonic slow muscle is a rapid model for testing gene editing technologies in
      vivo and uncovering gene functions in muscle cell differentiation.

PMID- 29374851
TI  - Morbidity of local therapy for locally advanced metastatic breast cancer: an
      analysis of the Surveillance, Epidemiology, and End Results (SEER)-Medicare
      Registry.
AB  - PURPOSE: Limited data exist to guide the management of in-breast tumors that can
      produce physical and emotional discomfort in the setting of metastatic disease.
      We evaluated the morbidity of local therapy (LT) among patients with locally
      advanced metastatic breast cancer. METHODS: Patients with de novo T4M1 breast
      cancer diagnosed between 2005 and 2011 were identified from the SEER-Medicare
      database. We assessed receipt of care for loco-regional morbidity before and
      after LT. RESULTS: Among 3660 patients with T4M1 disease, 1558 (43%) underwent LT
      [surgery (19%), radiation (15%), both (9%)]. Before LT, few patients were
      reported to have loco-regional morbidity (7.9% vs. 6.7% for no LT, P = 0.17).
      Following LT, patients were reported to have more loco-regional morbidity than
      patients who did not have LT (22.6% vs. 7.9%). More patients without baseline
      loco-regional morbidity were reported to have received care for loco-regional
      morbidity documented after LT compared to baseline loco-regional morbidity
      reported in patients without LT (19.9% vs. 6.3%, P < 0.001). CONCLUSIONS: The
      need to address loco-regional morbidity is relatively infrequent among patients
      with T4M1 disease who do not undergo LT. Receipt of care for loco-regional
      morbidity was higher following LT. For patients without existing loco-regional
      morbidity, risks of LT may outweigh potential benefits.

PMID- 29374850
TI  - Pathological Bases and Clinical Impact of Intratumor Heterogeneity in Clear Cell
      Renal Cell Carcinoma.
AB  - PURPOSE OF REVIEW: Intratumor heterogeneity is an inherent event in tumor
      development that is receiving much attention in the last years since it is
      responsible for most failures of current targeted therapies. The purpose of this
      review is to offer clinicians an updated insight of the multiple manifestations
      of a complex event that impacts significantly patient's life. RECENT FINDINGS:
      Clear cell renal cell carcinoma is the most common renal tumor and a paradigmatic
      example of a heterogeneous neoplasm. Next-generation sequencing has demonstrated
      that intratumor heterogeneity encompasses genetic, epigenetic, and
      microenvironmental variability. Currently accepted protocols of tumor sampling
      seem insufficient in unveiling intratumor heterogeneity with reliability and need
      to be updated. This variability challenges the precise morphological diagnosis,
      its molecular characterization, and the selection of optimal personalized
      therapies in clear cell renal cell carcinoma, a neoplasm traditionally considered
      chemo- and radio-resistant. We review the state of the art of the different
      approaches to intratumor heterogeneity in clear cell renal cell carcinomas, from
      the simple morphology to the most sophisticated massive sequencing tools.

PMID- 29374852
TI  - Lymphovascular invasion after neoadjuvant chemotherapy is strongly associated
      with poor prognosis in breast carcinoma.
AB  - PURPOSE: Few studies evaluated the prognostic value of the presence of
      lymphovascular invasion (LVI) after neoadjuvant chemotherapy (NAC) for breast
      cancer (BC). METHODS: The association between LVI and survival was evaluated in a
      cohort of BC patients treated by NAC between 2002 and 2011. Five post-NAC
      prognostic scores (ypAJCC, RCB, CPS, CPS + EG and Neo-Bioscore) were evaluated
      and compared with or without the addition of LVI. RESULTS: Out of 1033 tumors,
      LVI was present on surgical specimens in 29.2% and absent in 70.8% of the cases.
      Post-NAC LVI was associated with impaired disease-free survival (DFS) (HR 2.54;
      95% CI 1.96-3.31; P < 0.001), and the magnitude of this effect depended on BC
      subtype (Pinteraction = 0.003), (luminal BC: HR 1.83; P = 0.003; triple negative
      BC: HR 3.73; P < 0.001; HER2-positive BC: HR 6.21; P < 0.001). Post-NAC LVI was
      an independent predictor of local relapse, distant metastasis, and overall
      survival; and increased the accuracy of all five post-NAC prognostic scoring
      systems. CONCLUSIONS: Post-NAC LVI is a strong independent prognostic factor
      that: (i) should be systematically reported in pathology reports; (ii) should be
      used as stratification factor after NAC to propose inclusion in second-line
      trials or adjuvant treatment; (iii) should be included in post-NAC scoring
      systems.

PMID- 29374853
TI  - A high-risk 70-gene signature is not associated with the detection of tumor cell
      dissemination to the bone marrow.
AB  - PURPOSE: The 70-gene signature (70-GS) is a prognostic tool, grouping patients in
      risk groups to assess their need for adjuvant chemotherapy. Tumor cell
      dissemination to the bone marrow is a marker of minimal residual disease and
      associated with impaired survival. In this study, we aimed to evaluate whether 70
      GS is associated with the presence of disseminated tumor cells (DTCs) in the bone
      marrow of patients with early breast cancer. METHODS: In patients with hormone
      receptor-positive HER2-negative early breast cancer, the 70-GS was obtained and
      the presence of DTCs was immunohistochemically evaluated using cytokeratin
      staining with the A45-B/B3 antibody. RESULTS: 149 patients were included into the
      analysis. 40 (27%) had a high-risk 70-GS and 35 (23%) had detectable DTCs in
      their bone marrow. 9 (22%) of the 40 patients with high-risk 70-GS and 26 (24%)
      of the 109 patients with a low-risk 70-GS were positive for DTCs (p = 0.863).
      CONCLUSIONS: As both 70-GS and DTC detection are known prognostic factors but do
      not seem to correlate, a follow-up on a larger cohort is warranted to evaluate if
      a combination of the two is able to better stratify the relapse risk in early
      breast cancer patients.

PMID- 29374854
TI  - Liraglutide ameliorates palmitate-induced insulin resistance through inhibiting
      the IRS-1 serine phosphorylation in mouse skeletal muscle cells.
AB  - OBJECTIVE: A reduction in insulin-stimulated glucose uptake in skeletal muscles
      is a characteristic of insulin resistance and type 2 diabetes mellitus (T2DM).
      The glucagon-like peptide (GLP)-1 agonist liraglutide can reduce blood glucose
      levels in individuals with T2DM. However, its effect on insulin-induced glucose
      metabolism in the skeletal muscle of insulin resistance is unknown. We
      investigated the effects and action mechanisms of liraglutide on insulin
      resistance (IR) in the skeletal muscle cells treatment with palmitic acid (PA).
      METHODS: The cell-surface GLUT4myc levels were determined by an antibody-coupled
      colorimetric assay. The phosphorylation levels of Akt, PI3K(p85alpha), AS160,
      IRS1, IKK, and JNK were determined by western blotting. The quantifications of
      mRNA levels of TNFalpha, IL-1beta, and IL-6 were determined by real-time PCR.
      Analysis of variance was used for data analysis. RESULTS: PA elevated not only
      phosphorylation of JNK, IRS1 serines, and IKKalpha/beta, but also the expression
      of IL-6, TNFalpha and IL-1beta in C2C12-GLUT4myc cells. PA can reduce
      phosphorylation of IRS1 tyrosine. These effects of PA were reversed by
      liraglutide. In addition, liraglutide can reverse PA-decreased insulin-stimulated
      cell-surface GLUT4 levels, Akt, PI3K(p85alpha), and AS160 phosphorylation.
      CONCLUSIONS: Liraglutide can enhance insulin-induced GLUT4 translocation by
      inhibiting IRS1 serine phosphorylation in PA-treated muscle cells.

PMID- 29374855
TI  - Children on dialysis as well as renal transplanted children report severely
      impaired health-related quality of life.
AB  - OBJECTIVES: To assess health-related quality of life (HRQoL) across three renal
      replacement therapy modalities (preemptive transplant, non-preemptive transplant,
      and dialysis) in comparison with the healthy norm and other chronic health
      conditions, and to explore related patient factors. STUDY DESIGN: All prevalent
      end-stage renal disease (ESRD) patients aged 8-18 years who spent at least 6
      months on their current treatment modality in the Netherlands, Belgium, and part
      of Germany were approached to complete the Pediatric Quality of Life Inventory
      4.0 (PedsQLTM) questionnaire. We determined the differences between groups on
      PedsQLTM mean scores, the proportion of children with an impaired HRQoL (>= 1 SD
      lower than the healthy norm), the proportion of problems on individual items of
      the PedsQLTM, and the effect of time on current treatment. Linear regression
      models were used to explore determinants of HRQoL. RESULTS: 192 out of 278
      patients (20% preemptive transplant, 58% non-preemptive transplant, 22% dialysis)
      filled in the PedsQLTM (response rate 69%). Independent of treatment modality,
      patients had significantly lower mean scores and consequently higher proportions
      of impaired HRQoL on almost all domains compared to the healthy norm and other
      chronic health conditions. Patients with a preemptive transplant only reported
      higher scores on physical health compared to the other treatment modalities.
      Having comorbidities was the most important determinant associated with lower
      HRQoL scores. CONCLUSION: Dialysis and renal transplantation both have a severe
      impact on the HRQoL of children with ESRD. Physicians should be aware of this
      continuous burden. Furthermore, to develop tailored interventions for children
      with ESRD, qualitative studies are needed to gain more insight in the
      determinants of HRQoL in the different treatment modalities.

PMID- 29374856
TI  - Disparities in women's cancer-related quality of life by Southern Appalachian
      residence.
AB  - PURPOSE: The purpose was to determine whether Appalachian residence alone or in
      combination with violence was linked to poorer quality of life (QOL). METHODS:
      Women recently diagnosed and included in either the Kentucky or North Carolina
      Cancer Registries were interviewed by phone between 2009 and 2015 (n = 3320; mean
      age = 56.74). Response rates were similar by state (40.1 in Kentucky and 40.9% in
      North Carolina). Appalachian (N = 990) versus non-Appalachian residents (N =
      2330) were hypothesized to have poorer QOL defined as (a) lower Functional
      Assessment of Cancer Therapy-General (FACT-G) scores and (b) more symptoms of
      depression, stress, or comorbid physical conditions. Lifetime intimate partner or
      sexual violence was first investigated as a moderator then mediator of regional
      differences. Multiple analyses of covariance (MANCOVA) models were used. RESULTS:
      Violence modified the effect of Appalachian residence on poorer QOL outcomes;
      FACT-G total scores (p = .02) were lowest for women living in Appalachia who had
      additionally experienced violence. Socioeconomic indicators appeared to mediate
      or explain differences in QOL outcomes by Appalachian residence such that when
      adjusting for income, education and insurance, Appalachian residence remained
      associated only with poorer physical QOL outcomes (p < .05). CONCLUSIONS: While
      violence rates did not differ by residence, the combined effect of living in
      Appalachia and experiencing violence resulted in significantly greater impact on
      poorer QOL among women recently diagnosed with cancer. Clinical consideration of
      patients' residence, socioeconomic status and violence experienced may help
      identify and mitigate the longer-term impact of these identifiable factors
      associated with poorer QOL.

PMID- 29374857
TI  - Dentate nucleus T1 hyperintensity: is it always gadolinium all that glitters?
AB  - In the last few years, several scientific papers and reports have demonstrated
      magnetic resonance (MR) signal intensity (SI) changes on pre-contrast T1-weighted
      images following multiple gadolinium-based contrast agents (GBCA)
      administrations, particularly following the exposure to linear GBCAs.
      Pathological animal and human post-mortem studies have confirmed the relationship
      between this radiological finding and the presence of gadolinium accumulation in
      vulnerable brain regions in patients with normal renal function. In this short
      communication, we report the case of a 15-year-old patient affected by b-cell
      acute lymphoblastic leukemia (bALL) who developed a hyperintense signal in the
      dentate nuclei following multiple administrations of a macrocyclic GBCA. The
      purpose of this report is to discuss possible differential diagnoses of this
      radiological finding with special focus on the differentiation between iron or
      manganese accumulation, post-irradiation changes and GBCA-related Gd deposition,
      highlighting the importance of the acquisition of accurate clinical data to
      improve our scientific knowledge.

PMID- 29374858
TI  - Tools for Visualizing HIV in Cure Research.
AB  - PURPOSE OF REVIEW: The long-lived HIV reservoir remains a major obstacle for an
      HIV cure. Current techniques to analyze this reservoir are generally population
      based. We highlight recent developments in methods visualizing HIV, which offer a
      different, complementary view, and provide indispensable information for cure
      strategy development. RECENT FINDINGS: Recent advances in fluorescence in situ
      hybridization techniques enabled key developments in reservoir visualization.
      Flow cytometric detection of HIV mRNAs, concurrently with proteins, provides a
      high-throughput approach to study the reservoir on a single-cell level. On a
      tissue level, key spatial information can be obtained detecting viral RNA and DNA
      in situ by fluorescence microscopy. At total-body level, advancements in non
      invasive immuno-positron emission tomography (PET) detection of HIV proteins may
      allow an encompassing view of HIV reservoir sites. HIV imaging approaches provide
      important, complementary information regarding the size, phenotype, and
      localization of the HIV reservoir. Visualizing the reservoir may contribute to
      the design, assessment, and monitoring of HIV cure strategies in vitro and in
      vivo.

PMID- 29374860
TI  - Blood Collection and Cell-Free DNA Isolation Methods Influence the Sensitivity of
      Liquid Biopsy Analysis for Colorectal Cancer Detection.
AB  - During colorectal cancer (CRC) development tumor-derived cell-free DNA (cfDNA)
      can be released into the bloodstream. Many different cfDNA isolation methods and
      specific blood collection tubes preventing the release of genomic DNA and
      stabilizing cfDNA with preservative reagents became available. These factors may
      affect greatly on the further liquid biopsy analyses. Our aim was to test
      different blood collection tubes and cfDNA isolation methods to determine whether
      these factors influence the cfDNA amount and the promoter methylation of four
      previously described hypermethylated biomarkers. Three manual isolation methods
      (High Pure Viral Nucleic Acid Large Volume Kit; Epi proColon 2.0 Kit; Quick
      cfDNATM Serum & Plasma Kit) and automated sample preparation systems (InviGenius
      and InviGenius PLUS) were examined. Furthermore, K3EDTA Vacuette tubes and Streck
      Cell-Free DNA BCT(r) tubes were compared. After cfDNA isolation and bisulfite
      conversion of samples, the methylation level of SFRP1, SFRP2, SDC2, and PRIMA1
      were defined with MethyLight assays. We have ascertained that there are
      differences between the cfDNA amounts depending on the isolation methods. Higher
      cfDNA yield was observed using InviGenius system than column-based manual
      isolation method; however, InviGenius PLUS has produced lower cfDNA amounts. No
      remarkable variance could be found between K3EDTA and Streck tubes; slightly
      higher cfDNA quantity was detected in 60% of plasma samples using Streck tubes.
      In point of methylation level and frequency, manual column-based isolation
      produced more consistent results. Automated cfDNA extraction systems are easy-to
      use and high-throughput; however, further improvements in the isolation protocols
      might lead to the increase of the sensitivity of further methylation analysis.

PMID- 29374861
TI  - Air quality and acute myocardial infarction in adults during the 2016 Hangzhou
      G20 summit.
AB  - To fulfill its commitment to a successful Hangzhou G20 summit (4 to 5 September
      2016), the Chinese government implemented a series of measures to improve the air
      quality in Hangzhou. We report findings on air quality and acute myocardial
      infarction (AMI) hospital admissions in adults during the Hangzhou G20 summit.
      Three study periods were defined. The first period was pre-G20 (28 July to 27
      August: limited restrictions on industrial emissions). The second period was G20
      (28 August to 6 September) when there were further restrictions on industrial
      emissions and increased transportation restrictions. The third period was post
      G20 (7 September to 6 October) when restrictions were relaxed again. The mean
      number of AMI admissions per day was, respectively, 8.2 during G20, 13.3 during
      pre-G20, and 15.1 during post-G20. We used time-series Poisson regression models
      to estimate the relative risk (RR) for AMI associated with pollution levels. Our
      results suggest that the air quality improvement can reduce the number of
      hospital admissions for AMI.

PMID- 29374859
TI  - Clinical and Economic Outcomes of Interventions to Reduce Antipsychotic and
      Benzodiazepine Use Within Nursing Homes: A Systematic Review.
AB  - BACKGROUND: Antipsychotic and benzodiazepine medications are widely used in
      nursing homes despite only modest efficacy and the risk of severe adverse
      effects. Numerous interventions have been implemented to reduce their use.
      However, the outcomes for the residents and staff and the economic impact on the
      healthcare system remain relatively understudied. OBJECTIVE: The aim was to
      examine the clinical and economic outcomes reported within interventions to
      reduce antipsychotic and/or benzodiazepine use in nursing homes. METHODS:
      Databases searched included PubMed, EMBASE, CINAHL, CENTRAL, Scopus, and
      ProQuest. We focussed on interventions with professional (e.g. education) and/or
      organisational (e.g. formation of multidisciplinary teams) components. Data were
      extracted from the papers that included clinical and/or economic outcomes. Two
      authors independently reviewed articles for eligibility and quality. RESULTS:
      Fourteen studies reported on clinical outcomes for the residents: 13
      antipsychotic reduction studies and one study focussing exclusively on
      benzodiazepine reduction. There was substantial heterogeneity in the types of
      outcomes reported and the method of reporting. Change in behavioural and
      psychological symptoms was the most commonly reported outcome throughout the
      antipsychotic reduction interventions (n = 12 studies) and remained stable or
      improved in ten of 12 studies. Whilst improvements were seen in emotional
      responsiveness, measures of sleep, cognitive function, and subjective health
      score remained unchanged upon benzodiazepine reduction. No interventions included
      an economic analysis. CONCLUSIONS: Efforts should be made to improve the
      consistency in reporting of clinical outcomes within interventions to reduce
      antipsychotic and/or benzodiazepine medications. Additionally, the economic
      impact of these interventions should be considered. Nonetheless, evidence
      suggests that interventions that reduce antipsychotic use are unlikely to have
      deleterious clinical effects. The clinical and economic effects of benzodiazepine
      reduction remain under-reported.

PMID- 29374862
TI  - Organic fertilizer application increases the soil respiration and net ecosystem
      carbon dioxide absorption of paddy fields under water-saving irrigation.
AB  - Quantifying carbon sequestration in paddy soil is necessary to understand the
      effect of agricultural practices on carbon cycles. The objective of this study
      was to assess the effect of organic fertilizer addition (MF) on the soil
      respiration and net ecosystem carbon dioxide (CO2) absorption of paddy fields
      under water-saving irrigation (CI) in the Taihu Lake Region of China during the
      2014 and 2015 rice-growing seasons. Compared with the traditional fertilizer and
      water management (FC), the joint regulation of CI and MF (CM) significantly
      increased the rice yields and irrigation water use efficiencies of paddy fields
      by 4.02~5.08 and 83.54~109.97% (p < 0.05). The effects of organic fertilizer
      addition on soil respiration and net ecosystem CO2 absorption rates showed inter
      annual differences. CM paddy fields showed a higher soil respiration and net CO2
      absorption rates during some periods of the rice growth stage in the first year
      and during most periods of the rice growth stage in the second year. These fields
      also had significantly higher total CO2 emission through soil respiration (total
      Rsoil) and total net CO2 absorption compared with FC paddy fields (p < 0.05). The
      total Rsoil and net ecosystem CO2 absorption of CM paddy fields were 67.39~91.55
      and 129.41~113.75 mol m-2, which were 27.66~135.52 and 12.96~31.66% higher than
      those of FC paddy fields. The interaction between water and fertilizer management
      had significant effects on total net ecosystem CO2 absorption. The frequent
      alternate wet-dry cycles of CI paddy fields increased the soil respiration and
      reduced the net CO2 absorption. Organic fertilizer promoted the soil respiration
      of paddy soil but also increased its net CO2 absorption and organic carbon
      content. Therefore, the joint regulation of water-saving irrigation and organic
      fertilizer is an effective measure for maintaining yield, increasing irrigation
      water use efficiency, mitigating CO2 emission, and promoting paddy soil
      fertility.

PMID- 29374863
TI  - Photodegradation of 2,4-dichlorophenol by supported Pd(X2) catalyst (X = Cl, Br,
      N3): a HOMO manipulating point of view.
AB  - Three different palladium(II) complexes with ligands containing nitrogenized
      aromatic rings were investigated theoretically as model to obtain the
      computational band gap energies. The results demonstrated promising possibility
      for designing palladium(II) complexes with photocatalytic properties at visible
      light irradiation. Deliberated products were synthesized via grafting on the
      silica-coated Fe3O4 magnetic nanoparticles (Fe3O4@SiO2). Formation of complexes
      on the surface of Fe3O4@SiO2, as insoluble and reusable photocatalysts, was
      proved by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction
      (XRD), thermogravimetric (TGA), X-ray photoelectron spectroscopy (XPS), vibrating
      sample magnetometer (VSM), transmission electron microscope (TEM), and scanning
      electron microscopy (SEM) analyses. The trend of the band gap energies of
      prepared structures was calculated via experimental and theoretical methods. The
      photocatalytic capability of these nanoparticles was investigated in degradation
      of 2,4-dichlorophenol by means of HPLC analysis. A tentative reaction mechanism
      for the formation of intermediates was proposed. Graphical abstract ?.

PMID- 29374864
TI  - [Coping with rabies outbreak in Israel].

PMID- 29374865
TI  - [FUNCTIONAL TRAJECTORIES BEFORE, DURING AND AFTER ACUTE HOSPITALIZATION OF OLDER
      ADULTS IN INTERNAL MEDICINE WARDS].
AB  - INTRODUCTION: Hospital-associated functional decline (HAFD) is recognized as a
      leading cause of adverse hospitalization outcomes, such as prolonged
      hospitalization, falls, readmission, and mortality. Since most patients
      hospitalized in internal medicine wards are older-adults, HAFD presents a major
      challenge to internal medicine. OBJECTIVES: Describe functional trajectories of
      older-adults (aged >=70 years) before, during and after acute hospitalization in
      internal-medicine units. METHODS: A prospective cohort study was conducted of 741
      older-adults, hospitalized in two tertiary hospitals in Israel during the period
      2009-2011. Basic functional status two weeks before admission, on-admission, at
      discharge and one-month post-discharge was assessed using the modified Barthel
      Index (BI). Eight trajectories were identified. RESULTS: Two-thirds of the
      participants were completely or almost independent at the pre-morbid period.
      About a half of the older-adults were hospitalized with pre-admission functional
      decline, a quarter deteriorated or died during hospitalization, and one-third
      improved during hospitalization. Most of the older-adults who were stable in
      functioning at the pre-admission period (57.1%) remained stable during and post
      hospitalization; however, about a third of them did not return to their pre
      morbid functioning levels. Approximately half of those with pre-morbid functional
      decline experienced additional deterioration of at least 5 points on the BI
      scale. Pre-morbid instrumental functional status, comorbidity and depressive
      symptoms have been found to distinguish older adults with similar pre-admission
      and in-hospital functional trends. DISCUSSION: Eight functional trajectories
      describe the hospitalization period of older-adults in internal-medicine units.
      On-admission personal characteristics may be used to identify older-adults who
      are at risk of unwarranted hospitalization outcomes and thus allow intervention
      in the hospital-community interface.

PMID- 29374866
TI  - [THE NATIONAL FINAL INTERNAL MEDICINE EXAMINATION SCORE - IS IT PREDICTABLE?]
AB  - INTRODUCTION: There is no current medical licensing examination in Israel (2016).
      The only objective indicators which reflect students' medical knowledge and basic
      clinical reasoning skills are the national medical examination scores. The aim of
      the present study was to investigate the nature of the relationship between
      students' demography, gender and academic achievements during their pre-clinical
      studies and their final national internal medicine examination scores. METHODS:
      The study was based on data collected by the Technion information system. The
      study cohort consisted of medical students admitted to the Technion Faculty of
      Medicine over a decade from 2005-2014, via a standard admission procedure.
      Students accepted on the basis of former academic achievement were not part of
      this cohort. The cohort was divided into three, based on the level of success in
      the final national examination in internal medicine. CONCLUSIONS: Our main
      conclusions were: (1) the admission screening criteria (scores of matriculation
      and psychometric tests) are helpful markers for predicting success in the final
      examination in internal medicine; (2) students who performed the psychometric
      tests in the Arabic language have relatively lower-achieving grades in the final
      examination in internal medicine in comparison to students taking the same
      psychometric exam in the Hebrew language. Furthermore, (3) high achievements in
      core preclinical courses and especially in the "integrative course" in the first
      2 trimesters of the fourth year of studies are relatively strong predictors for
      success in the final examination in internal medicine.

PMID- 29374867
TI  - [SOCIAL-ECONOMIC-DEMOGRAPHIC DIFFERENCES IN REASONS NOT TO COMPLY IN TIME WITH
      ROUTINE CHILDHOOD VACCINATIONS].
AB  - BACKGROUND: In recent years, there has been an increase in parents who do not
      comply with recommended routine vaccines. The vaccination coverage rates in
      Israel are known, but the reasons for not completing immunizations are unknown.
      The aim of this study was to assess the extent of failure to complete the routine
      vaccinations in time and the reasons among different population groups. METHODS:
      This is a retrospective case-control cohort study, among children born in 2009. A
      total of 14,232 medical records of children who received services at Mother-Child
      Health Clinics were checked. The children who received all three core vaccines
      (3th Hepatitis B, 4th DTaP and MMR vaccines) were considered fully compliant and
      those missing at least one vaccination were considered non-compliant. Six reasons
      for not complying were identified: medical reasons, parental refusal to
      vaccinate, requests for a deferred schedule of vaccinations, parental behavior,
      organizational reasons and others. The differences between groups were analyzed
      by univariate analysis and logistic regression. RESULTS: In this study, 7.4% of
      children, were not fully compliant with all three core vaccines within two years.
      The main reasons in the Jewish population were: refusal and requests for
      variation in scheduling (44.3%) and in the Arabic population: parental behavior
      (40.8%). The risk for not completing the vaccinations was higher in children of
      Jewish mothers, residence in the Hadera sub-district, parents who had an academic
      education and older parents. CONCLUSIONS: There are differences between Arab and
      Jewish populations in the reasons for not complying in time with childhood
      vaccinations. In order to obtain herd immunity in the Israeli population, we need
      to tailor interventions suitable for each population group according to their
      characteristics.

PMID- 29374868
TI  - [LAPAROSCOPICALLY-ASSISTED ULTRASOUND-GUIDED PERCUTANEOUS TRANSABDOMINAL OOCYTE
      COLLECTION: FERTILITY PRESERVATION IN A 17-YEARS-OLD GIRL WITH VAGINAL EWING
      SARCOMA].
AB  - INTRODUCTION: Options for preserving fertility in children and adolescents with
      cancer depend on patient age, the available time frame, and the treatment
      regimen. Ovarian stimulation with mature oocyte preservation is often the optimal
      method in post-menarcheal adolescents. We describe a case of a 17-year-old girl
      with vaginal soft-tissue Ewing sarcoma in whom transvaginal oocyte collection for
      fertility preservation was ruled out by the large tumor. To overcome the
      limitations of the transabdominal approach, we applied a novel method of
      laparoscopically-assisted ultrasound-guided percutaneous transabdominal oocyte
      collection. In this manner, we were able to both perform oophorectomy and obtain
      superficial and deep ovarian follicles for cryopreservation.

PMID- 29374869
TI  - [SOCIAL IMPACT BONDS FOR HEALTH PROMOTION AND PREVENTIVE MEDICINE].
AB  - INTRODUCTION: The World Health Organization (WHO) has declared obesity a global
      epidemic. WHO sheds much light on this matter in its publications on health
      promotion and preventative medicine. Lack of physical activity, an unbalanced
      diet and an unhealthy lifestyle are the leading causes of developing obesity and
      chronic diseases. In Israel, the growing rate of obesity is a reason for concern.
      About 500,000 diabetics, mainly as a result of obesity, live in Israel today and
      by 2030 the number is expected to rise to 2,000,000. Every third child born is
      expected to develop diabetes by the time they reach the age of 40 unless a
      profound change is made in health policy. The State of Israel recognizes its
      responsibility in promoting awareness against obesity as well as its role in
      prevention. In spite of the country's recognition of the problem, it still has
      not managed to implement long term solutions which address the issue. Therefore,
      creative and innovative solutions are called for. The social impact bond (SIB), a
      newly developed financial model is a possible solution. This model suggests the
      entry of private investors into the public sector, a field which is within the
      responsibility of the government. The private investor will be in charge of
      running a social program on a topic which will be finalized with the government.
      The private investor and the government will have a contract outlining the
      program and the criteria for the evaluation and the success of the program. To
      note, the private investor will only be paid according to the success of the
      program. Thus the purpose of SIB is in motion processes and is set to serve as a
      model for several years, and then the authorities will take over the
      responsibility and continue with the program that the SIB handled. In March 2016,
      a new SIB was launched in Israel to prevent Type 2 diabetes. This involves 2250
      pre-diabetic adults who are at risk to develop Type 2 diabetes and will be
      identified by their Health Maintenance Organizations (HMOs, Clalit and Leumit)
      through blood tests. The participants will take part in an intensive intervention
      wellness program during 3 years. This SIB aims to prevent the onset of diabetes.
      If successful, and a significant reduction in Type 2 diabetes is found, there
      will be substantial savings for the HMOs and the National Insurance Institute,
      which will in turn repay the investors for their expenses, according to the
      signed contract. This SIB will serve as a pilot project for diabetes prevention
      and if successful, this model can be adopted for other projects in preventive
      medicine and health promotion. Thereby, we may be facing a dramatic change in the
      paradigm of funding national health services in Israel.

PMID- 29374870
TI  - [THE SYNDROME OF COMBINED PULMONARY FIBROSIS AND EMPHYSEMA - CPFE].
AB  - INTRODUCTION: There is an increasing recognition of patients with radiologic
      features of both pulmonary fibrosis and emphysema. This association has enabled
      the description of a syndrome termed combined pulmonary fibrosis and emphysema
      (CPFE) with unique features. Patients are mostly male smokers who suffer from
      effort dyspnea and hypoxemia, with near-normal spirometric and lung volumes
      measurements, and abnormalities of gas exchange. On the computerized tomography
      there is upper-lobe emphysema and lower-lobe interstitial fibrosis. CPFE is
      frequently complicated by pulmonary hypertension, lung cancer, acute lung injury
      and coronary artery disease. Mortality is significant, especially in the presence
      of pulmonary hypertension. In this article we will review the CPFE syndrome.

PMID- 29374871
TI  - [SHOULD EVERY WOMAN AFTER LABOR BE OFFERED PELVIC FLOOR PHYSIOTHERAPY?]
AB  - INTRODUCTION: Pelvic floor damage can occur during pregnancy, during childbirth
      or post-partum, and may be expressed by symptoms such as urinary incontinence,
      fecal and gas incontinence, sexual dysfunction, pelvic organ prolapse and chronic
      pelvic pain. Some of the symptoms, which manifest later in a woman's life, will
      go unrecognized in the immediate postpartum period. Most women do not mention
      their general health, unless specifically asked. Physiotherapists, who are adept
      with the anatomy of the musculoskeletal system and the ability to diagnose unique
      differences, can aid in the diagnosis and treatment of postpartum pelvic floor
      problems. Monitoring, pelvic floor physiotherapy and exercise can be effective
      both in treatment and prevention of functional disorders of the pelvic floor. In
      this article, we will discuss pelvic floor problems and their appearance
      throughout pregnancy and childbirth, and the means of treatment from the
      physiotherapist's perspective. We raise the question as to whether all postpartum
      women could benefit from a training program of pelvic floor muscles. Pelvic floor
      physiotherapy is included in the health basket in Israel, but is not broadly
      utilized. Wider use could be adopted, particularly in light of the latest
      research evidence.

PMID- 29374872
TI  - [FORCE-FEEDING OR LIFE-SAVING? - DEALING WITH HUNGER STRIKES IN ISRAEL].
AB  - INTRODUCTION: Force feeding of fasting hunger-striking prisoners is the subject
      of considerable controversy in Israel and elsewhere, posing a direct conflict
      between two basic ethical values: that of human life and respect for autonomy.
      The Israel Medical Association, as well as the World Medical Association, has
      taken the position that force feeding of such prisoners is an act of torture and
      is therefore unethical. However this paper presents an opposing view, which
      recently became the law in Israel, that, whereas the rights of prisoners to
      decree a hunger strike as a form of protest should be respected, if the
      prolongation of the strike reaches a stage of clear and present danger to the
      life and health of a prisoner, the saving of the prisoner's life must take
      precedence over considerations of autonomy. The paper present the steps that
      should be taken, including extensive and empathic efforts to persuade the
      prisoner to end his/her fast; gaining the approval of a hospital's ethics
      committee; and gaining the approval of a district court judge; the feeding is to
      be carried out in the most humane and sensitive manner as befitting a lifesaving
      procedure for any patient. This position is consistent with Israel's Basic Law:
      Human Dignity and Liberty, Israel's Patient Rights Law, Israel's "Do not stand
      idly by your fellow man's blood" Law, with several Israeli court decisions and in
      keeping with the dominant Israeli culture. Finally, instructions for physicians
      who object to such measures are discussed, ascertaining the freedom of conscience
      as well as preserving the life of the hunger-strikers.

PMID- 29374873
TI  - [A hunger strike and force-feeding of prisoners in Israel].

PMID- 29374874
TI  - [FORCE-FEEDING OR LIFE-SAVING? - DEALING WITH HUNGER STRIKES IN ISRAEL].
AB  - INTRODUCTION: Although the management of quality of care by the health funds has
      contributed to its improvement, medical teams criticize the way it is performed.
      Many call for renewed values-driven thinking and to leave the concern for quality
      in the hands of the medical teams, relying on "self control and enforcement",
      based on values, compassion, concern for others, patient service, discipline and
      personal responsibility. This article aims to present an economic perspective on
      the measurement of quality of care. It places the development of "measuring the
      quality of care and its management" within the development of the organization of
      care, health insurance and payment arrangements for medical teams. The conclusion
      is that there is no "first best" method to improve the quality of care. Each
      method - including the quantitative-functional measurement-based method used in
      many systems and the value-driven, self enforced method proposed by many - has
      advantages and disadvantages. The choice of a method should be based on these two
      sides, discussed jointly by medical teams, the health funds, hospitals and the
      Health Ministry.

PMID- 29374875
TI  - [TRMU MUTATIONS - REVERSIBLE INFANTILE LIVER FAILURE OR MULTISYSTEM DISORDER?]
AB  - INTRODUCTION: Bi-allelic mutations in the TRMU gene cause reversible infantile
      liver failure. Little is known about extra-hepatic manifestations in these
      patients. BACKGROUND: Two infants, aged 4 and 5 months, presented with
      progressive life threatening liver failure, characterized by lactic acidosis,
      highly elevated alpha-fetoprotein and recurrent hypoglycemia. Both showed
      significant extra-hepatic findings, including: hypothyroidism, macrocytic anemia
      and microcephaly. Both were of Jewish Yemenite descent and homozygous for Y77H
      mutation in the TRMU gene. CONCLUSIONS: TRMU bi-allelic mutations cause severe
      life-threatening liver failure. Extra-hepatic involvement is common and should be
      evaluated. Spontaneous resolution and recovery occurs in most patients with a
      remarkably good long-term prognosis. Liver failure in a Jewish-Yemenite infant
      should prompt early genetic testing for TRMU Y77H mutation. Pediatricians should
      be aware of this disease and the common mutation in Israel. DISCUSSION: Nineteen
      additional patients were described in the literature, of whom 13 were from
      Israel; 6/19 (31%) manifested extra-hepatic involvement, namely: myopathic
      weakness, cardiomyopathy, renomegaly and proteinuria, bulbar dysfunction,
      cerebral white matter changes and abnormal growth including microcephaly.
      Mortality was 24% (5/21). Survivors (16/21, 76%) showed complete recovery and
      resolution of clinical, laboratory and histologic abnormalities. Most Israeli
      patients (10/15) were of Jewish-Yemenite ancestry. Homozygous Y77H genotype was
      exclusive to this patient subgroup and was associated with a 100% survival and
      recovery rate.

PMID- 29374876
TI  - [SOLITARY KIDNEY - IS IT TOO LITTLE?]
AB  - INTRODUCTION: Solitary functioning kidney (SFK) occurs with unilateral renal
      agenesis (URA) in 1/2000 live births - or after uninephrectomy for tumor, trauma,
      uncontrolled infections or hypertension and post-kidney donation. URA-associated
      states include urological, cardiac, gastrointestinal and skeletal anomalies or it
      might be a component of a genetic syndrome. In 10% of cases of URA another family
      member is affected. In any case of SFK a compensatory process is triggered
      consisting of glomerular hypertension with hyperfiltration which achieves 75% of
      two kidneys' function. In the long-run this process might be detrimental causing
      further loss of functioning nephrons, inability to sustain functional
      compensation and progressive kidney function deterioration. The risk for this
      chain of events is determined in the first place by the number of nephrons in the
      SFK, which cannot be assessed in vivo. Hints for reduced nephron number in the
      single kidney include prematurity or SGA-small for date birth weight, urological
      anomalies with or without accompanying infections, lack of increased single
      kidney size - compensatory hypertrophy. Age of onset of the compensatory process
      and acquired factors including nephrotoxin exposure, overweight/obesity,
      excessive salt and/or protein intake contribute to the risk of progressive renal
      damage. Life-long follow-up of all subjects with SFK is recommended from early
      age for lifestyle education: recommended diet and tailored physical activity,
      nephrotoxin avoidance along with early detection of renal injury signs:
      albuminuria, hypertension or depressed kidney function - GFR (glomerular
      filtration rate) targeting timely intervention for preservation of functioning
      renal mass.

PMID- 29374877
TI  - [Making contributions to healthy China].

PMID- 29374879
TI  - [Guideline of preconception and prenatal care(2018)].

PMID- 29374878
TI  - [Chinese guideline for diagnosis and management of polycystic ovary syndrome].

PMID- 29374880
TI  - [PCOS: through the lens of experience, evidence-based, and precision medicine].

PMID- 29374881
TI  - [Effect of hyperandrogenism on obstetric complications of singleton pregnancy
      from in vitro fertilization in women with polycystic ovary syndrome].
AB  - Objective: To compare the difference in risks of obstetric complications of
      singleton pregnancy between women with hyperandrogenic polycystic ovary syndrome
      (PCOS) and women with normoandrogenic PCOS. Methods: Prospective cohort study.
      This study was a secondary analysis of data collected during a multicenter
      randomized controlled clinical trial. Women who got clinical singleton pregnancy
      were grouped according to whether they were diagnosed with hyperandrogenism at
      baseline. There were 118 women with hyperandrogenism and 366 women without
      hyperandrogenism. The incidences of obstetric complications and birth weight were
      compared between the two groups. Results: Women with hyperandrogenic PCOS had a
      significantly higher risk of preterm delivery than women with normoandrogenic
      PCOS [12.7% (15/118) versus 3.6% (13/366); OR=3.94, 95%CI: 1.82-8.56]. After
      adjustment of age, duration of infertility, body mass index, and fresh or frozen
      embryo transfer group, hyperandrogenism was still associated with an increased
      risk of preterm delivery (OR=3.67, 95%CI: 1.67-8.07). Compared with women with
      normoandrogenic PCOS, women with hyperandrogenic PCOS had similar risks of
      pregnancy loss, gestational diabetes mellitus, pre-eclampsia, placenta previa,
      and postpartum hemorrhage (all P>0.05). Birth weight as well as the risks of
      being small for gestational age and large for gestational age were also
      comparable between the two groups (all P>0.05). Conclusion: In women with PCOS
      and singleton pregnancy, those with preconceptional hyperandrogenism have a
      higher risk of preterm delivery than those without hyperandrogenism.

PMID- 29374882
TI  - [Value of anti-Mullerian hormone in predicting pregnant outcomes of polycystic
      ovary syndrome patients undergone assisted reproductive technology].
AB  - Objective: Explore the value of anti-Mullerian hormone (AMH) in predicting
      pregnant outcomes of polycystic ovary syndrome (PCOS) patients undergone assisted
      reproductive technology. Methods: The study totally recruited 1 697 patients who
      underwent the first in vitro fertilization (IVF) or intracytoplasmic sperm
      injection (ICSI) cycle in Sun Yat-sen Memorial Hospital from the January 2014 to
      December 2015. The patients were divided into two groups based on the age<35
      (n=758) and >=35 years old (n=939) , compare the basic data and pregnant outcomes
      of controlled ovarian hyerstimulation. Spearman correlation method was conducted
      to analyze the relations between AMH and clinical outcomes. The logistic
      regression method and partial correlation analysis were used to judge the main
      factors which determine pregnancy outcomes by controlled the confounding factors.
      The receiver operating characteristic curve (ROC) was used to evaluate the
      predictive sensitivity and specificity of AMH. Results: In the group of PCOS
      patient younger than 35 years, AMH were correlated with the number of antral
      follicles (r=0.388) and retrieved oocytes (r=0.235) . When the effect of total
      dosage and starting dosage of gonadotropin were controlled, AMH was still
      significantly associated with the number of retrieved oocytes (P<0.05) . AMH had
      no predictive value for the clinical pregnancy of PCOS patient younger than 35
      years (area under ROC curve=0.481, P=0.768) . In the group of PCOS patient>=35
      years old, AMH were correlated with the number of antral follicles (r=0.450) ,
      retrieved oocytes (r=0.399) , available embryo (r=0.336) and high quality embryo
      (r=0.235) . When the effect of total dosage and starting dosage of gonadotropin
      were controlled, the correlations were still significant between those indexes
      (all P<0.05) . AMH had no predictive value for the clinical pregnancy of PCOS
      patient >=35 years old (area under ROC curve=0.535, P=0.560) . However, the
      clinical pregnancy rate of the group of PCOS patient >=35 years old was slightly
      higher than the control group (P=0.062) . Conclusions: AMH has no predictive
      value for the pregnancy outcome of PCOS patient. The pregnancy rate of PCOS
      patient >=35 years old is slightly higher than the younger group, because the
      PCOS patient may have better ovarian reserve.

PMID- 29374883
TI  - [Analysis of pregnancy outcomes of polycystic ovary syndrome patients after
      frozen embryo transfer].
AB  - Objective: To investigate pregnancy outcomes of the patients with polycystic
      ovary syndrome (PCOS) after frozen embryo transfer (FET) . Methods: Data of 2 367
      PCOS patients received in vitro fertilization-embryo transfer [including fresh
      embryo transfer (fET) and FET] from January 2009 to December 2015 in Peking
      University Third Hospital were evaluated retrospectively. The basal
      characteristics, pregnancy complications and outcomes were analyzed, then
      identified the relative factors followed. Results: Totally 2 367 patients
      received in vitro fertilization-embryo transfer: 1 106 were treated with fET, and
      the rest 1 261 cases were treated with FET. The incidence of gestational diabetes
      mellitus (GDM) was lower in FET group [4.04%(51/1 261) versus 6.15%(68/1 106)],
      the difference was statistically significant (P<0.05). Singletons born after FET
      had higher birth weight than fET [(3 406+/-548) versus (3 360+/-533) g], the
      difference was statistically significant (P<0.05). There was no difference of
      other pregnancy complications between the two groups (all P>0.05). fET was an
      independent risk factor for GDM (adjusted OR=1.570, 95%CI: 1.075-2.294).
      Conclusion: Compared with fET, FET could decrease the risk of GDM and receive
      better neonatal outcomes in patients with PCOS.

PMID- 29374884
TI  - [Chinese expert consensus on the diagnosis and treatment of Herlyn-Werner
      Wunderlich syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome and vaginal
      atresia].

PMID- 29374885
TI  - [Clinical outcome of therapeutic cervical cerclage in short cervix syndrome].
AB  - Objective: To investigate the clinical effect of therapeutic cervical cerclage on
      short cervix syndrome for anti-premature birth in the second trimester. Methods:
      Totally 44 singleton pregnant patients were diagnosed as short cervix syndrome,
      which was cervical length <=2.5 cm without cervical dilatation, and received
      treatment from January 2008 and July 2015 in Peking University Third Hospital
      were collected. Among them, 30 patients who received therapeutic cervical
      cerclage were defined as cerclage group and another 14 cases who received
      conservative treatment were defined as un-cerclage group. The days of
      conservative treatment, delivery rate of different gestational weeks, birth
      weight of newborns, neonatal survival rate within 7 days of birth were analyzed
      between the two groups. Results: There were no significant differences between
      the two groups in days of pregnancy conservative treatment [103 (84-141) vs 105
      (85-114) days], delivery weeks [38.0 (35.5-39.4) vs 38.5 (37.3-39.5) weeks],
      birth weight of newborns [3 120 (2 750-3 400) vs 3 130 (2 760-3 545) g], and
      survival rate of newborns [100% (30/30) vs 13/14]. The fetuses of both groups
      were all delivered after 28 weeks. There was no significant difference in
      accumulated delivery rate between the two groups after 32 weeks, 34 weeks, and 37
      weeks, respectively (all P>0.05) . Conclusions: The treatment of cervical
      cerclage is not superior to conservative means in single pregnancy of cervical
      length <=2.5 cm without cervical dilatation. For such patients with short cervix
      syndrome, the treatment of cervical cerclage may not be necessary, but dynamic
      monitoring and search for the causing factors and prompt treatment are more
      important.

PMID- 29374886
TI  - [Some reflections on evidenced-based medicine, precision medicine, and big data
      based research].
AB  - Evidence-based medicine remains the best paradigm for medical practice. However,
      evidence alone is not decisions; decisions must also consider resources available
      and the values of people. Evidence shows that most of those treated with blood
      pressure-lowering, cholesterol-lowering, glucose-lowering and anti-cancer drugs
      do not benefit from preventing severe complications such as cardiovascular events
      and deaths. This implies that diagnosis and treatment in modern medicine in many
      circumstances is imprecise. It has become a dream to identify and treat only
      those few who can respond to the treatment. Precision medicine has thus come into
      being. Precision medicine is however not a new idea and cannot rely solely on
      gene sequencing as it was initially proposed. Neither is the large cohort and
      multi-factorial approach a new idea; in fact it has been used widely since 1950s.
      Since its very beginning, medicine has never stopped in searching for more
      precise diagnostic and therapeutic methods and already made achievements at
      various levels of our understanding and knowledge, such as vaccine, blood
      transfusion, imaging, and cataract surgery. Genetic biotechnology is not the only
      path to precision but merely a new method. Most genes are found only weakly
      associated with disease and are thus unlikely to lead to great improvement in
      diagnostic and therapeutic precision. The traditional multi-factorial approach by
      embracing big data and incorporating genetic factors is probably the most
      realistic way ahead for precision medicine. Big data boasts of possession of the
      total population and large sample size and claims correlation can displace
      causation. They are serious misleading concepts. Science has never had to observe
      the totality in order to draw a valid conclusion; a large sample size is required
      only when the anticipated effect is small and clinically less meaningful;
      emphasis on correlation over causation is equivalent to rejection of the
      scientific principles and methods in epidemiology and a call to give up the
      assurance for validity in scientific research, which will inevitably lead to
      futile interventions. Furthermore, in proving the effectiveness of intervention,
      analyses of real-world big data cannot displace the role of randomized controlled
      trial. We expressed doubts and critiques in this article on precision medicine
      and big data, merely hoping to stimulate discussing on the true potentials of
      precision medicine and big data.

PMID- 29374887
TI  - [Sex-specific associations between tobacco smoking and risk of cardiovascular
      diseases in Chinese adults].
AB  - Objective: To examine the sex-specific associations between tobacco smoking and
      risk of cardiovascular diseases in Chinese adults. Methods: The present analysis
      included 487 373 participants from the China Kadoorie Biobank after excluding
      those with cancer, heart diseases, stroke at baseline survey. The baseline survey
      was conducted from June 2004 to July 2008. The number of follow-up years was
      calculated from the time that the participants completed baseline survey to the
      time of any event: CVD incidence, death, loss of follow-up, or December 31, 2015,
      whichever occurred first. We used Cox proportional hazards regression models to
      estimate the HRs and 95%CI of incident cardiovascular diseases with tobacco
      smoking. Results: During a median follow-up of 8.9 years(a total of 4.1 million
      person years), we documented 33 947 cases of ischemic heart diseases, 6 048 cases
      of major coronary diseases, 7 794 cases of intracerebral hemorrhage, and 31 722
      cases of cerebral infarction. The prevalence of smoking was much higher in men
      (67.9%) than in women (2.7%). Smoking increased risk of all subtypes of
      cardiovascular diseases. Compared with nonsmokers, the multivariable-adjusted HRs
      (95% CI) for current smokers were 1.54 (1.43-1.66) for major coronary event, 1.28
      (1.24-1.32) for ischemic heart disease, 1.18 (1.14-1.22) for cerebral infarction,
      and 1.07 (1.00-1.15) for intracerebral hemorrhage, respectively. Female smokers
      tended to have greater risk of developing major coronary event associated with
      amount of tobacco smoked daily (interaction P=0.006) and age when smoking started
      (interaction P=0.011). There was no sex difference in these two effects for
      ischemic heart diseases, intracerebral hemorrhage and cerebral infarction (all
      interaction P>0.05). Conclusions: This prospective study confirmed increased risk
      of all subtypes of cardiovascular diseases in current smokers. Smoking was more
      harmful to women than to men for major coronary event.

PMID- 29374888
TI  - [Risk factors related to HIV new infections among men who have sex with men in a
      cohort study].
AB  - Objectives: To analyze and understand the risk factors related to HIV new
      infections among men who have sex with men (MSM). Methods: A longitudinal
      observational study among MSM was conducted to collect information on HIV related
      behaviors and sero-conversion. Univariate and multivariate generalized estimating
      equations (GEE) were used to discuss the risk factors for HIV new infection.
      Results: A total number of 4 305 MSM were followed during 2013-2015. Among those
      self-reported MSM who are seeking partners on the Interner tended to have higher
      proportion on receptive anal intercourse and consistent condom use during anal
      intercourse than the subgroups seeking their partners in gay bars or bathrooms.
      HIV incidence among followed MSM during the study period appeared as 4.3/100
      person years, with adjusted RR (aRR) of HIV infection for receptive anal
      intercourse as group 2.20 (95% CI: 1.49-3.24) times than that of insertion anal
      intercourse group. Those who used rush-poppers (aRR=1.55, 95% CI: 1.10-2.17),
      unprotected anal intercourse (aRR=2.24, 95%CI: 1.62-3.08), and those with
      syphilis infection (aRR=2.95, 95%CI: 2.00-4.35) were also risk factors for HIV
      new infections. After controlling other factors, the relationship between the
      ways of seeking partners and HIV new infection was not statistical significant.
      Conclusion: Risk factors for HIV new infection among MSM appeared complex and
      interactive, suggesting that further studies are needed to generate tailored
      strategies for the prevention of HIV epidemic among MSM population.

PMID- 29374889
TI  - [Sources and characteristics of newly reported HIV/AIDS cases in Yiwu, Zhejiang
      province, 2015-2016].
AB  - Objective: To understand the sources and characteristics of newly reported
      HIV/AIDS cases in Yiwu, Zhejiang province, from 2015 to 2016. Methods: From
      January 1, 2015 to December 31, 2016, newly reported HIV/AIDS cases in Yiwu were
      recruited in the study and they were asked to complete an in-depth field
      epidemiology questionnaire. Information related to their previous sexual
      behaviors and infection sources or routes were collected in the survey. The data
      were processed and analyzed with EpiData 3.0 and SPSS 19.0 software. Results: A
      total of 320 participants from 393 newly reported HIV/AIDS cases in Yiwu during
      this period were surveyed and recruited in the study. Most of them were males
      (268, 83.8%), unmarried (141, 44.1%), aged between 25-44 years (166, 51.9%), had
      census register in other provinces (217, 67.8%) and educational level of junior
      high school (128, 40.0%). Among 305 cases whose infection times could be
      determined, 107 (35.1%) were newly infected within one year, and among 267 cases
      whose infection location could be determined, 200 (74.9%) were infected in Yiwu.
      New infections were mainly detected in those who had homosexual behaviors or
      causal sex partners (during the past year) and through active detection approach.
      Local infections were mainly among those who had local residence and commercial
      heterosexual behavior in Yiwu. Conclusions: Most newly reported HIV/AIDS cases in
      Yiwu from 2015-2016 were infected for more than one year and locally infected.
      Census registration of other provinces, homosexual sexual behavior, and casual
      sexual behavior give major contribution to HIV/AIDS epidemic in Yiwu.

PMID- 29374890
TI  - [Deaths attributable to alcohol use and its impact on life expectancy in China,
      2013].
AB  - Objective: To analyze the deaths attributable to alcohol use and its impact on
      people's life expectancy in China in 2013. Methods: The mortality data from the
      Disease Surveillance Points System and alcohol use data from China Chronic
      Disease Surveillance (2013) were used. The deaths attributed to alcohol use and
      its impact on the life expectancy of Chinese residents were estimated based on
      the principle of comparative risk assessment by calculating population
      attributable fraction. Results: In 2013, alcohol use resulted in 381 200 deaths,
      including 97 100 hemorrhagic stroke deaths, 88 200 liver cancer deaths, 61 400
      liver cirrhosis deaths and 48 700 esophageal cancer deaths, and prevented 76 500
      deaths, including 68 500, 4 900 and 3 100 deaths which might be caused by
      ischemic heart disease, hemorrhagic stroke and diabetes respectively. If risk
      factor of alcohol use is removed, the people's life expectancy would rise by an
      average of 0.43 years, especially in western China by 0.52 years, which was 0.12
      years higher than that in eastern and central China, and the life expectancy of
      the population in rural and urban areas would rise by 0.48 years and 0.31 years
      respectively. Conclusions: Although alcohol has a protective effect on reducing
      ischemic heart disease, stroke and diabetes deaths, alcohol use is still a risk
      factor influencing the mortality and life expectancy of residents in China. It is
      necessary to take targeted measures to reduce the health problems caused by
      harmful use of alcohol.

PMID- 29374891
TI  - [Epidemiological analysis on mortality of cancer in China, 2015].
AB  - Objective: To understand the distribution of cancer deaths in China in 2015 and
      provide reference for the prevention and control of cancer. Methods: Based on the
      results of Global Burden of Disease 2015, the cancer death distributions in
      different age groups, sex groups, provinces or by different malignant tumor in
      Chinese were described. Results: The age-standardized mortality rate of cancer
      was 159.01/100 000 in China in 2015. The mortality rate was highest in age group
      >=70 years (1 102.73/100 000), and lowest in age group 5-14 years (5.40/100 000).
      The mortality rate in males was 2.15 times higher than that in females. The first
      5 provinces with high cancer mortality rate were Anhui, Qinghai, Sichuan, Guangxi
      and Henan. Lung cancer, liver cancer, stomach cancer, esophageal cancer and
      colorectal cancer ranked 1-5 in term of mortality rate. Conclusion: The cancer
      mortality differed with age, gender, area and different malignant tumors,
      suggesting the necessity to develop targeted prevention and control strategies.

PMID- 29374892
TI  - [Trend of cancer mortality in Hebei province, 1973-2013].
AB  - Objective: To analyze the data of malignant tumor mortality and change in disease
      burden in Hebei province from 1973 to 2013. Methods: Cancer mortality rate, age
      standardized mortality rate and the years of life lost due to premature mortality
      (YLLs) were calculated by using the data from three rounds of all death causes
      survey and database of cancer registry in Hebei during 1973-2013. Results: From
      1973 to 2013, a linear upward of malignant tumor mortality was observed, with a
      51.57% increase. The mortality rate during 1973-1975 was 98.52/100 000 and it was
      149.33/100 000 during 2011-2013. During 1973-1975, the YLLs was 17.0/1 000 in
      males and 12.8/1 000 in females. While during 2011-2013, the YLLs was 23.2/1 000
      in males and 15.9/1 000 in females. During 1973-1975, esophagus cancer, stomach
      cancer and liver cancer were top three leading causes of deaths. During 2011
      2013, lung cancer, stomach cancer and liver cancer were main leading causes of
      deaths. During the past 40 years, the deaths of esophagus cancer and cervix
      cancer decreased dramatically, but the deaths of lung cancer and breast cancer
      increased sharply. Conclusions: The disease burden caused by malignant tumor is
      becoming more serious in Hebei. It is necessary to strengthen the primary
      prevention and screening of malignant tumor.

PMID- 29374893
TI  - [Epidemiology of human rabies in China, 2016].
AB  - Objective: To understand the epidemiological characteristics of human rabies in
      China in 2016 and provide evidence for the control and prevention of human
      rabies. Methods: The incidence data of human rabies in China in 2016 were
      collected from national infectious disease reporting information management
      system. The surveillance data were collected from provinces of Shandong, Guizhou,
      Anhui, Hunan, Jiangsu and Guangxi Zhuang Autonomous Region. Excel 2013 software
      was used to process and summarize the data, the epidemiological characteristics
      of human rabies in China in 2016 were described by using indicators such as
      morbidity, mortality and constituent ratio. Results: A total of 644 human rabies
      cases were reported in 28 provinces in China in 2016, a decrease of 19.60%
      (157/801) compared with 2015. The provinces reporting high incidences of human
      rabies were Henan, Hunan, Guangxi and Guizhou, accounting for 39.44% (254/644) of
      the total cases. One case was reported in Qinghai province and Xinjiang Uygur
      Autonomous Region respectively. The male to female ratio of the cases was 2.14?1
      (439/205), and the majority of the patients were farmers (444/644). Surveillance
      points in 6 provinces reported 1 281 340 persons seeking post-exposure treatment,
      of whom 1 018 367 were treated for dog bite or scratch. A total of 764 234
      persons completed the vaccination series, accounting for 63.90% (764 234/1 195
      956) of the persons with grade II and III exposures, and 28.89% (165 677/573 571)
      of the persons with grade III exposure were treated with passive immunization
      product. The average density of dogs in each surveillance area was 7.03/100
      persons, the average canine immunization rate was 37.64%. Conclusion: The
      incidence of human rabies has remained decline in China in 2016, the number of
      the affected provinces has increased and that has the tendency of spreading to
      low-risk regions. The cases mainly occurred in men and farmers, and caused by dog
      bite or scratch. It is necessary to strengthen the health education about rabies
      prevention and control in rural areas and expand the coverage of canine
      immunization to prevent and control human rabies.

PMID- 29374894
TI  - [Epidemiology of human infection with avian influenza A(H7N9) virus in China,
      2013-2017].
AB  - Objective: To understand the epidemiological characteristics of human infection
      with avian influenza A (H7N9) virus in China, and provide evidence for the
      prevention and control of human infection with H7N9 virus. Methods: The published
      incidence data of human infection with H7N9 virus in China from March 2013 to
      April 2017 were collected. Excel 2007 software was used to perform the analysis.
      The characteristics of distribution of the disease, exposure history, cluster of
      the disease were described. Results: By the end of April 2017, a total of 1 416
      cases of human infection with H7N9 virus were confirmed in China, including 559
      deaths, the case fatality rate was 39.5%. In 2016, the case number was lowest
      (127 cases), with the highest fatality rate (57.5%). The first three provinces
      with high case numbers were Zhejiang, Guangdong and Jiangsu. The median age of
      the cases was 55 years and the male to female ratio was 2.3?1. Up to 66% of cases
      had clear live poultry exposure history before illness onset, 31% of cases had
      unknown exposure history and only 3% of the cases had no live poultry exposure
      history. There were 35 household clusters (5 in 2013, 9 in 2014, 6 in 2015, 5 in
      2016, 10 in 2017), which involved 72 cases, accounting for 5% of the total cases.
      Conclusions: The epidemic of human infection with H7N9 virus in China during 2013
      2017 had obvious seasonality and spatial distribution. There was limited family
      clustering. Infection cases were mostly related to poultry contact.

PMID- 29374895
TI  - [Temporal-spatial analysis of bacillary dysentery in the Three Gorges Area of
      China, 2005-2016].
AB  - Objective: To analyze the spatial and temporal distributions of bacillary
      dysentery in Chongqing, Yichang and Enshi (the Three Gorges Area) from 2005 to
      2016, and provide evidence for the disease prevention and control. Methods: The
      incidence data of bacillary dysentery in the Three Gorges Area during this period
      were collected from National Notifiable Infectious Disease Reporting System. The
      spatial-temporal scan statistic was conducted with software SaTScan 9.4 and
      bacillary dysentery clusters were visualized with software ArcGIS 10.3. Results:
      A total of 126 196 cases were reported in the Three Gorges Area during 2005-2016,
      with an average incidence rate of 29.67/100 000. The overall incidence was in a
      downward trend, with an average annual decline rate of 4.74%. Cases occurred all
      the year round but with an obvious seasonal increase between May and October.
      Among the reported cases, 44.71% (56 421/126 196) were children under 5-year-old,
      the cases in children outside child care settings accounted for 41.93% (52
      918/126 196) of the total. The incidence rates in districts of Yuzhong, Dadukou,
      Jiangbei, Shapingba, Jiulongpo, Nanan, Yubei, Chengkou of Chongqing and districts
      of Xiling and Wujiagang of Yichang city of Hubei province were high, ranging from
      60.20/100 000 to 114.81/100 000. Spatial-temporal scan statistic for the spatial
      and temporal distributions of bacillary dysentery during this period revealed
      that the temporal distribution was during May-October, and there were 12 class I
      clusters, 35 class II clusters, and 9 clusters without statistical significance
      in counties with high incidence. All the class I clusters were in urban area of
      Chongqing (Yuzhong, Dadukou, Jiangbei, Shapingba, Jiulongpo, Nanan, Beibei,
      Yubei, Banan) and surrounding counties, and the class II clusters transformed
      from concentrated distribution to scattered distribution. Conclusions: Temporal
      and spatial cluster of bacillary dysentery incidence existed in the three gorges
      area during 2005-2016. It is necessary to strengthen the bacillary dysentery
      prevention and control in urban areas of Chongqing and Yichang.

PMID- 29374896
TI  - [Epidemiology of scrub typhus and influencing factors in Yunnan province, 2006
      2013].
AB  - Objective: To understand the epidemiological characteristics of scrub typhus and
      influencing factors in Yunnan province, and provide further information for the
      prevention and control of scrub typhus. Methods: Based on the incidence data of
      scrub typhus reported in Yunnan from 2006 to 2013, the epidemiological
      characteristics of scrub typhus were analyzed and related environmental factors
      were identified with panel negative binomial regression model. Results: A total
      of 8 980 scrub typhus cases were reported during 2006-2013 in Yunnan. The average
      annual incidence was 2.46/100 000, with an uptrend observed. Natural focus
      expansion was found, affecting 71.3% of the counties in 2013. The epidemic mainly
      occurred in summer and autumn with the incidence peak during July-October. The
      annual incidence was higher in females than in males. More cases occurred in
      children and farmers, the proportions of cases in farmers and pre-school aged
      children showed an obvious increase. Panel negative binomial regression model
      indicated that the transmission risk of scrub typhus was positive associated with
      monthly temperature and monthly relative humidity. Furthermore, an "U" pattern
      between the risk and the increased coverage of cropland and grassland as well as
      an "inverted-U" pattern between the risk and increased coverage of shrub were
      observed. Conclusion: It is necessary to strengthen the scrub typhus surveillance
      in warm and moist areas as well as the areas with high coverage of cropland and
      grassland in Yunnan, and the health education in children and farmers who are at
      high risk.

PMID- 29374897
TI  - [Analysis on epidemiological and temporal-spatial distribution characteristics of
      hemorrhagic fever with renal syndrome in Shandong province, 2010-2016].
AB  - Objective: To analyze the epidemiological and temporal-spatial distribution
      characteristics of hemorrhagic fever with renal syndrome (HFRS) in Shandong
      province during 2010-2016 and provide references for developing prevention and
      control measures. Methods: Based on the data of Infectious Disease Reporting
      Information System in China, the incidence and temporal-spatial distribution of
      HFRS in Shandong from 2010 to 2016 were analyzed by spatial autocorrelation and
      space-time scan statistics. Results: A total of 9 114 HFRS cases were reported in
      Shandong during this period. The cases were mainly distributed in age group 30-70
      years, and the male to female ratio of the cases was 2.63 ? 1. Most cases were
      farmers. The higher incidence rate was reported in southeastern Shandong, while
      the lower incidence rate was reported in northwestern Shandong. Among the
      epidemic periods, the highest incidence rate was 1.87/100 000 in 2013. The
      results of spatial autocorrelation and space-time scanning indicated that the
      high-high clusters of HFRS were concentrated in southeastern Shandong and then
      spread to central Shandong. The cluster mainly occurred from the end of 2011 to
      the first half of 2015. Both the incidence rate and the cluster decreased in
      2016. Conclusions: The epidemic and cluster of HFRS still existed in Shandong
      from 2010 to 2016. The key areas for the prevention and control of HFRS were in
      southeastern and central Shandong.

PMID- 29374898
TI  - [Circulation and etiological characterization of Salmonella enterica serotype in
      human in Guangdong province, 2007-2016].
AB  - Objective: To understand the circulation, drug resistance and molecular
      characteristics of Salmonella1, 4, [5], 12: i:- in human in Guangdong province.
      Methods:Salmonella1, 4, [5], 12: i:- isolated from diarrhea patients in Guangdong
      during 2007-2016 were detected for drug resistance, genes and PFGE
      characteristics. Results: A total of 2 960 strains Salmonella1, 4, [5], 12: i: -
      were isolated from human diarrhea cases during this period. The positive rates of
      the isolation increased year by year. The male to female ratio of the infection
      cases was 1.58?1, and the infection mainly occurred in infants and young
      children. Except imipenem, Salmonella1, 4, [5], 12: i: - was resistant to other
      17 antibiotics to some extent. The drug resistant rates to ceftazidime,
      cefotaxime and ciprofloxacin increased from 2011 to 2016. Multi-drug resistance
      was serious, for example, the multi-drug resistant strains with ASSuT accounted
      for 70.62% (435/616) and the multi-drug resistant strains with ACSuGSTTm
      accounted for 27.11% (167/616). The lack of fljA, fljB and hin genes, as well as
      the retaining of iroB, STM2740, STM2757 genes, resulted in the unable expression
      of FljBenx gene with 8 different defection profiles. There were 934 different
      PFGE patterns observed in 2 347 strains, which displayed a relatively large
      fingerprint polymorphism. The major PFGE pattern was JPXX01. GD0226, which was
      found in 97 strains, accounting for 4.13% (97/2 347). The PFGE patterns in 168
      Salmonella1, 4, [5], 12: i: - strains were consistent with that of Salmonella
      typhimurium. Conclusions:Salmonella1,4,[5], 12: i: - strains has become the major
      serotype of Salmonella that cause diarrhea in human in Guangdong. The multi-drug
      resistance of Salmonella1,4, [5], 12: i: - was serious, and since the defection
      of fljA, fljB and hin genes, the expression of FljBenx protein failed. The PFGE
      results were diverse, which displayed polymorphism in inheritance.

PMID- 29374899
TI  - [Characteristic and dynamic of HIV-1 subtype distribution in men who have sex
      with men in Guangzhou, 2008-2015].
AB  - Objective: To understand the characteristics and dynamic of HIV-1 subtype
      distribution in men who have sex with men (MSM) in Guangzhou between 2008 and
      2015. Methods: HIV-1 RNAs were extracted from serum samples of the individuals
      newly diagnosed with HIV-1 infection among MSM living in Guangzhou between 2008
      and 2015. The pol gene segments of HIV-1 genome from these RNA samples were
      amplified by nested reverse transcription polymerase chain reaction (nested-PCR)
      and were sequenced. Subsequently, the phylogenetic tree was reconstructed using
      pol sequences of samples and references together and the subtype of HIV-1 was
      determined. The distributions of HIV-1 subtypes detected in MSM with different
      demographic characteristics in different years were compared. Results: A total of
      2 210 pol gene segments were successfully obtained from 2 473 serum samples of
      the MSM. The average age of 2 210 MSM was 30.19 years with standard deviation of
      8.22 years, the unmarried MSM and those in Han ethnic group accounted for 73.39%
      and 90.81%, respectively. The proportion of subtype CRF07_BC (38.10%) was
      highest, followed by CRF01_AE (34.84%), CRF55_01B (14.62%), B (6.06%), URFs
      (3.58%), CRF59_01B (2.17%) and other subtypes (0.63%). The annual proportions of
      subtype B (P=0.000, 99%CI:0.000-0.000), CRF07_BC (chi(2)=14.965, P=0.036),
      CRF55_01B (chi(2)=18.161, P=0.011) and URFs (P=0.001, 99% CI: 0.000-0.001) were
      significantly different. The proportion of subtype B showed a gradual decrease
      from 14.08% to 4.33% (P=0.000, 99%CI: 0.000-0.000), while the proportion of URFs
      rapidly increased from 0% to 6.40% (P=0.000, 99% CI: 0.000-0.000). The rate of
      URFs was significantly higher in farmers and migrant workers than in other groups
      (P=0.017, 99%CI: 0.014- 0.020) and the rate of URFs was higher in individuals who
      had multi sexual partners (chi(2)=5.733, P=0.017). Conclusions: CRF07_BC and
      CRF01_AE were the predominant HIV-1 subtypes and multiple subtypes co-circulated
      among MSM in Guangzhou between 2008 and 2015. The recombinations of HIV-1
      continue to occur in MSM. Strengthening behavioral intervention for farmers,
      migrant workers and individuals who have multi sexual partners has the important
      epidemiological significance against the emerging and circulating of the novel
      recombinant virus among MSM in Guangzhou.

PMID- 29374900
TI  - [Genetic characterization of norovirus isolated in an outbreak of gastroenteritis
      in Jiangsu province].
AB  - Objective: To analyze the genetic characterization of norovirus isolated in an
      outbreak of gastroenteritis in Jiangsu province. Methods: Extracted viral RNA
      from the swab samples of cases of acute gastroenteritis outbreak in Jiangsu
      province on December 16-27, 2016 was reversely transcribed to cDNA, and partial
      RNA-dependent RNA polymerase sequence and complete capsid sequence (VP1) were
      amplified by RT-PCR. Amplification products were sequenced for the analysis of
      genetic characteristics. Results: Based on sequence alignment, the variant shared
      a high level of identity with the strain GII.g isolated in Spain and Finland
      (98.7%) in the RNA-dependent RNA polymerase region, and with the strain GII.1
      isolated in American (99.4%) in the VP1. The recombination was determined by
      using software Simplot, and the breakpoint of recombination was located in the
      ORF1/2 overlap region at position 5 106 of VP1. The result of amino acids
      alignment in capsid region showed that there were no mutations in the amino acids
      of the predicted epitopes and receptor binding site I-III, but a unique amino
      acid change was detected at position 132 (N-S). Conclusion: The norovirus
      isolated in the outbreak of gastroenteritis in Jiangsu province was a rare
      recombinant norovirus variant GII.g-GII.1.

PMID- 29374901
TI  - [Association between rs10938397 polymorphism in GNPDA2 and obesity in children at
      different stages of development].
AB  - Objective: To examine the association between rs10938397 polymorphism in
      glucosamine-6-phosphate deaminase 2 (GNPDA2) and risk of obesity in children at
      different stages of development and analyze the differences in the association.
      Methods: A total of 3 503 school-aged children were selected from the Beijing
      Child and Adolescent Metabolic Syndrome (BCAMS) study in Beijing and their
      complete anthropometry weight, height, fat mass percentage (FMP), fat mass index
      (FMI) and free fat mass index (FFMI) and sexual maturation (SM) data were used.
      The developmental stages were evaluated using male testicular volume and female
      breast Tanner staging. FMP, FM and FFM were measured by bioelectrical impedance
      analysis. General obesity and adiposity were respectively defined according to
      Chinese sex-age-specific body mass index (BMI) cutoffs and sex-age-specific FMP
      cutoffs. The SNP rs10938397 were genotyped by the TaqMan Allelic Discrimination
      Assay with the GeneAmp 7900 sequence detection system (Applied Biosystems, Foster
      city, CA, USA). Relationships between rs10938397 polymorphism and BMI, FMP, FMI
      and FFMI and different types of obesity were tested using multivariate linear
      regression and logistic regression models. Results: After age adjustment and
      correction for multiple testing, the rs10938397-G was associated with BMI and
      risk of general obesity in boys in early puberty (beta=0.328, P=0.001; OR=1.420,
      95%CI: 1.126-1.790), and the rs10938397-G was associated with BMI in girls in
      late puberty (beta=0.266, P=0.001). The associations of GNPDA2 rs10938397-G with
      FFMI and FMI were observed in boys in early puberty (beta=0.137, P=0.016;
      beta=0.202, P=0.007) and the associations of rs10938397-G with FMP and FMI were
      observed in girls in late puberty (beta=0.153, P=0.002; beta=0.168, P=0.001). The
      rs10938397-G was also associated with adiposity in girls in late puberty
      (OR=1.339, 95%CI: 1.093-1.637). Conclusion: The rs10938397 polymorphism in GNPDA2
      is associated with adiposity in girls, and it is important to use an accurate
      indicator of obesity in exposing the genuine association between genes and
      obesity.

PMID- 29374902
TI  - [Analysis of community colorectal cancer screening in 50-74 years old people in
      Guangzhou, 2015-2016].
AB  - Objective: To analyze the effect of colorectal cancer screening in the general
      population in Guangzhou, and provide evidence for the for development of
      colorectal cancer screening policy and strategy. Methods: The data of colorectal
      cancer screening in Guangzhou during 2015- 2016 were collected. The
      participation, the positive rate of fecal occult blood test, the detection rate
      of colonoscopy and screening effect of colonoscopy were evaluated. Results: A
      total of 220 834 residents aged 50-74 years received the screening, and the
      positive rate of the screening was 16.77% (37 040 cases). Colonoscopy was
      performed for 7 821 cases (21.12%). Colorectal lesions were found in 4 126 cases
      (52.76%), of which 614 (7.85%) and 73 (0.93%) and 230 (2.94%) were identified as
      advanced adenoma, severe dysplasia lesions and colorectal cancers, respectively.
      The detection rates of all colorectal lesions were higher in men than in women
      (all P<0.01). The diagnostic rate of early lesion was 87.24%, and 99 early cancer
      cases were found, accounting for 46.26% of the total cases. The overall screening
      detection rate of colorectal cancer was 104.15/100 000, higher than the incidence
      rate (81.18/100 000) in colorectal cancer surveillance (P<0.001), but age group
      <70 years had higher detection rate, age group >=70 years had higher incidence
      rate. Conclusions: The colorectal cancer screening strategy in Guangzhou is
      effective in the detection of the population at high risk, increase the detection
      rate of colorectal lesions, early diagnosis rate of precancerous lesions and
      diagnosis rate of early colorectal cancer. The benefit in those aged <=69 years
      was more obvious than that in those aged 70-74 years. It is necessary to improve
      the compliancy of colorectal cancer screening in population at high risk.

PMID- 29374903
TI  - [Dynamic path analysis on life course epidemiology].
AB  - In the studies of modern epidemiology, exposure in a short term cannot fully
      elaborate the mechanism of the development of diseases or health-related events.
      Thus, lights have been shed on to life course epidemiology, which studies the
      exposures in early life time and their effects related to the development of
      chronic diseases. When exploring the mechanism leading from one exposure to an
      outcome and its effects through other factors, due to the existence of time
      variant effects, conventional statistic methods could not meet the needs of
      etiological analysis in life course epidemiology. This paper summarizes the
      dynamic path analysis model, including the model structure and significance, and
      its application in life course epidemiology. Meanwhile, the procedure of data
      processing and etiology analyzing were introduced. In conclusion, dynamic path
      analysis is a useful tool which can be used to better elucidate the mechanisms
      that underlie the etiology of chronic diseases.

PMID- 29374904
TI  - [Causality in objective world: Directed Acyclic Graphs-based structural parsing].
AB  - The overall details of causality frames in the objective world remain obscure,
      which poses difficulty for causality research. Based on the temporality of cause
      and effect, the objective world is divided into three time zones and two time
      points, in which the causal relationships of the variables are parsed by using
      Directed Acyclic Graphs (DAGs). Causal DAGs of the world (or causal web) is
      composed of two parts. One is basic or core to the whole DAGs, formed by the
      combination of any one variable originating from each time unit mentioned above.
      Cause effect is affected by the confounding only. The other is an internal DAGs
      within each time unit representing a parent-child or ancestor-descendant
      relationship, which exhibits a structure similar to the confounding. This paper
      summarizes the construction of causality frames for objective world research
      (causal DAGs), and clarify a structural basis for the control of the confounding
      in effect estimate.

PMID- 29374905
TI  - [Progress in research of family-based cohort study on common chronic non
      communicable diseases in rural population in northern China].
AB  - Family-based cohort study is a special type of study design, in which biological
      samples and environmental exposure information of the member in a family are
      collected and related follow up is conducted. Family-based cohort study can be
      applied to explore the effect of genetic factors, environmental factors, gene
      gene interaction, and gene-environment interaction in the etiology of complex
      diseases. This paper summarizes the objectives, methods and results, as well as
      the opportunities and challenges of the family-based cohort study on common
      chronic non-communicable diseases in rural population in northern China.

PMID- 29374906
TI  - [Progress in research of vaccination for patients with cancer].
AB  - Due to the tumor malignancy or immunosuppressive treatment, patients with cancer
      in general are more susceptible to vaccine-preventable infections. The types,
      timing, dose of vaccination or even the immunization program for them may differ
      from those for the normal persons. At present, it is recommended to use
      inactivated vaccines for patients with cancer rather than attenuated live
      vaccines, Vaccinations should be avoided during immunosuppressive therapy;
      patients with cancer should receive double dosage of hepatitis B vaccines and two
      doses of inactivated influenza vaccines yearly. This paper summarizes the
      progress in clinical trials of vaccination for cancer patients in foreign
      countries, and provide reference for the development and implementation of
      vaccination strategy for cancer patients in China.

PMID- 29374907
TI  - [Progress in research of relationship between heavy metal exposure and
      cardiovascular disease].
AB  - Heavy metal is one of pollutants existed widely in the environment, its
      relationship with cardiovascular disease has attracted more and more attention.
      In this review, the concentrations of heavy metals, including lead, cadium and
      asenic, in the body from several national surveillance networks and the
      epidemiological studies on the effects of the exposure of three heavy metals on
      cardiovascular system were summarized. It is suggested to strengthen nationwide
      surveillance for body concentrations of heavy metals in general population in
      order to provide baseline data for quantitative evaluation of the risk of heavy
      metal exposure on cardiovascular disease.

PMID- 29374908
TI  - [Donor specific antibodies and antibody mediated rejection].

PMID- 29374909
TI  - [A preliminary research on the exosome influenced by virus infection in the renal
      transplantation recipients].
AB  - Objective: Virus infection is a common complication of transplantation.With the
      research and application of exosome is becoming more popular, this study focused
      on whether the virus particles and nucleic acids exist in the exosomes extracted
      from the plasma of recipients with virus infection after renal transplantation.
      Methods: A total of 10 independent transplantation recipients at Institute of
      Organ Transplantation, 309th Hospital of Chinese People's Liberation Army from
      January 2015 to July 2017 were studied in this study.5 cases of positive or
      suspected positive in granulocytes HCMV pp65 antigen detection and positive in
      plasma HCMV DNA test, and the other 5 cases of positive results in plasma BK DNA
      test were adopted.Exosomes were extracted from the collected plasma samples with
      SBI kit.Electron microscopy and nanoparticles tracing analyzer (NTA) were used
      for exosome analysis.Quantitative real-time PCR method was used to inspect and
      compare virus DNA copies number in plasma, exosome and effluent. Results: Typical
      exosome-like vesicle structure was observed.NTA put forward the sample
      concentration data from 1.2 to 4.5*10(12) particles/ml, and the particle
      diameters were 30-200 nm.In the qRT-PCR assays, the viral DNA quantitative
      results of exosome samples are lower but on the same magnitude compared with that
      of the plasma, and sharply decreased in effluent. Conclusions: Virus DNAs in
      exosome samples of recipients with viral infection after transplantation were
      detected in great quantities.This not only hints the spread of the virus may take
      advantage of the biological formation process of exosomes, but also warns that
      the limitation of the existing way to extract exosmes from virus infected
      population may be a bottleneck in research.

PMID- 29374910
TI  - [Clinical efficacy of tonsillectomy in renal transplant patients with recurrent
      IgA nephropathy].
AB  - Objective: To investigate the therapeutic efficacy of tonsillectomy for patients
      with recurrence of IgA nephropathy (IgAN) after kidney transplantation. Methods:
      From May 2014, tonsillectomy was performed in 11 renal transplant patients with
      biopsy-proved recurrent IgAN. In a median follow-up of 14 (4-38) months, data of
      proteinuria, hematuria, estimated glomerular filtration rate (eGFR), and serum
      levels of IgA in these patients were compared before and after
      tonsillectomy.Patient's survival and renal graft survival were also summarized.
      Results: A remission of proteinuria was observed in 8 patients after
      tonsillectomy, and this status maintained well in the subsequent follow-up.Three
      patients had no or minimal reduction of proteinuria after tonsillectomy and
      returned to dialysis within 1 year after tonsillectomy.Possible causes could be
      severe primary IgAN of crescentric glomerulonephritis, IgAN recurrence in kidney
      retransplantation, and late tonsillectomy after IgAN recurrence.Serum levels of
      IgA significant decreased and no patients developed acute rejection or infection
      after tonsillectomy.In the 1-year follow-up, no patients died and grafts survived
      well in 8 out of 11 patients. Conclusions: Tonsillectomy may represent an
      effective and reliable way to treat recurrence IgAN after kidney transplantation,
      and may be applied widely in the future clinical management. However, early
      intervention is critical and effects may depend on the pathological features of
      primary IgAN.

PMID- 29374911
TI  - [Distribution and drug resistance of pathogens in infected organ donors from
      donation after the citizen death].
AB  - Objective: To investigate the distribution and drug resistance of pathogens in
      infected organ donors from donation after the citizen death (DCD). Methods:
      Clinical data of 217 DCD donors from January 2013 to June 2017 were
      retrospectively analyzed.The phlegm, urine, blood and drainage fluid from all of
      the donors were routinely cultured.The infection rate of the donors, the
      composition ratio of pathogens and the distribution of specimen sources were
      observed and the drug resistance was analyzed. Results: Of all the 217 donors,
      128 were infected and the infection rate was 59%.A total of 218 pathogens were
      isolated from these infected donors, including 55.5% (121/218) of gram-negative
      pathogens, 33.5% (73/218) of gram-positive pathogens followed by 11.0% (24/218)
      of fungi.The pathogenic specimens were mainly derived from sputum samples
      (72.5%), followed by urine (15.6%). The mainly two gram-negative pathogens were
      Klebsiella pneumonia and Acinetobacter baumannii.Klebsiella pneumonia exhibited
      varying degree of resistance to commonly used antibiotics, whereas susceptible to
      imipenem and meropenem.Acine-tobacterbaumannii was highly resistant to most of
      the antibiotics, and the drug resistance rate of imipenem and meropenem was over
      60%, displaying a tendency of multi-drug resistance.Staphylococcus aureus, as the
      mainly gram-positive pathogen, was generally resistant to penicillin and
      clindamycin, but still sensitive to tovancomycin, teicoplanin and linezolid.
      Conclusions: DCD donors have a high infection rate, and respiratory infection is
      most common. Gram-negative pathogens are the primary pathogens causing infection
      in DCD donors.Klebsiella pneumonia maintain susceptible to imipenem and
      meropenem, while Acinetobacter baumannii reveals a tendency of multi-drug
      resistance.Gram-positive pathogens are still sensitive to vancomycin, teicoplanin
      and linezolid.

PMID- 29374912
TI  - [Selective preimplantation pathological evaluation in renal transplantation: a
      single center's experience].
AB  - Objective: To summarize the clinical data of pre-implantation biopsy donors in
      our hospital and explore the clinical characteristics of those donors in
      pathological high-risk, and to provide references for the selective histological
      evaluation of extended criteria donor kidneys. Methods: We retrospectively
      reviewed the clinical data and pre-implantation renal pathologic score of donors
      from January 1, 2015 to May 1, 2017.During this period, 247 cases of donation
      after citizen's death (DCD) occurred.After clinical evaluation and selective
      machine perfusion( Lifeport) evaluation, 30 cases of pre-implantation
      pathological evaluation were performed.According to Remuzzi scores, donors were
      divided into low-risk and high-risk group.Nine cases of low-risk group (bilateral
      kidney's Remuzzi score <=3) and 16 cases of high-risk group (bilateral or
      unilateral kidney's Remuzzi score >=4, severe glomerular micro-thrombi or severe
      tubular necrosis) were included.Five cases of donors were excluded due to only
      unilateral renal pathological result available.Both high-risk and low-risk
      groups' clinical data, including sex, age, height, body weight, body mass index,
      proteinuria, hematuria, urinary glucose, baseline or admission serum creatinine,
      serum creatinine before procurement, history of hypertension and/or diabetes
      mellitus, cardiopulmonary resuscitation or not, with or without the history of
      shock, urine output prior to acquisition, macroscopical manifestations of donor
      kidney, cause of death were statistically analyzed. Results: The donors' baseline
      serum creatinine/upper limit of normal serum creatinine range in high-risk group
      were significantly higher than that in low-risk group [(129.8+/-42.2)% vs(92.4+/
      30.5)%, P=0.029]. The poor macroscopical manifestations of donor kidneys were
      significantly more frequent in high-risk group than that in low-risk group (12/16
      vs 0/9, P= 0). No significant differences between two groups were found regarding
      their age, height, weight, BMI, proteinuria, hematuria, urine glucose, pre
      procure creatinine level, history of hypertension and/or diabetes mellitus, cause
      of death and so on (P>0.05). Conclusions: After clinical evaluation and selective
      Lifeport evaluation, donor grafts of whose baseline serum creatinine levels
      increased beyond normal range and of whose grafts' macroscopical manifestations
      were poor, should undergo pre-implantation pathological evaluation further.Also,
      it is reasonable to perform pre-implantation biopsy in cases of equivocal results
      after Lifeport evaluation.This will be beneficial to identify histological high
      risk donors and also be predictive to allocate the grafts.

PMID- 29374913
TI  - [Correlation of serum level of homocysteine and insulin resistance with cognitive
      dysfunction in first-episode schizophrenics].
AB  - Objective: To explore the relationship of serum level of homocysteine (Hcy) and
      insulin resistance with cognitive function in first-episode drug-free
      schizophrenics. Methods: A total of 80 first-episode drug-free schizophrenics
      (schizophrenia group) from the First Affiliated Hospital of Zhengzhou University
      and 70 healthy individuals (control group) were enrolled.The serum concentration
      of Hcy was measured by the enzymatic cycling assay, the concentration of serum
      fast blood-glucose(FPG) by glucose oxidase method and fast insulin (FINS) by
      electrical chemiluminescence immunoassay.Then insulin resistance index was
      calculated in the form of HOMA-IR.Positive and Negative Syndrome Scale (PANSS)
      was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery
      (MCCB) was used to evaluate the cognitive function. Results: (1) The serum level
      of Hcy in schizophrenia group [(24+/-6) MUmoL/L]was significantly higher than
      that in control group[(16+/-4) MUmoL/L] (P<0.001). And the serum level of FINS in
      schizophrenia group [(8.0+/-2.1) mU/L] was significantly higher than that in
      control group[(6.0+/-1.3) mU/L] (P<0.001). The HOMA-IR of schizophrenia group
      (1.6+/-0.5) was higher than that of control group (1.3+/-0.4) (P<0.001). The
      serum level of Hcy in schizophrenia group had positive correlations with serum
      FINS level, HOMA-IR and negative symptoms (r=0.365, 0.354 and 0.233, all P<0.05).
      In comparison with the control group , scores were significantly lower in the
      seven domains of cognitive function in the schizophrenia group (all P<0.05). (2)
      In schizophrenia group, the serum level of Hcy had a negative correlation with
      Information processing rate P points, Attentional facilitating P points , and
      Verbal learning P points (r=-0.231, -0.339, -0.255, all P<0.05); the serum level
      of FINS was negatively related to Attentional facilitating P points, Working
      memory P pointsand Visual memory P points (r=-0.317, -0.309, -0.318, all P<0.05);
      HOMA-IR had a negative correlation with Attentional facilitating P points,
      Working memory P points, and Visual memory P points (r=-0.286, -0.224, -0.266,
      all P<0.05). After the influencing factors were adjusted by multiple regression,
      the associations of serum Hcy level with Information processing rate P points,
      Attentional facilitating P points and Verbal learning P points were still
      evident, and HOMA-IR was still related with Attentional facilitating P points and
      Visual memory P points (all P<0.05). Conclusion: The increase of serum Hcy and
      insulin resistance in first-episode schizophrenics, both have some relevance with
      cognitive dysfunction.

PMID- 29374914
TI  - [Regional homogeneity in the patients of irritable bowel syndrome complicated
      with depression: a resting-state functional magnetic resonance imaging study].
AB  - Objective: To explore the changes of the brain regional homogeneity (ReHo) in the
      patients of irritable bowel syndrome (IBS) complicated with depression by using
      resting-state functional magnetic resonance imaging (rs-fMRI) and to investigate
      the relation between abnormal brain function and depression in those patients.
      Methods: A total of 35 patients with IBS were included in this study, collected
      in Gastroenterology Department of Affiliated Hospital of Hangzhou Normal
      University from June 2015 to June 2017.According to Hamilton's Depression Scale
      (HAMD)-17 score, the IBS patients was divided into two groups: IBS with
      depression group, 21 cases and non-depression group, 14 cases.Thirty-six healthy
      controls were recruited at the mean time (gender, age and years of education were
      matched with the patients). Rs-fMRI and 3D T1 data were acquired with 3.0 T
      scanners.For all subjects, ReHo, a method measuring the synchronism of regional
      spontaneous activities, was calculated and one-way ANOVA was performed to assess
      the group effects.For those regions with significant group effects, correlation
      between ReHo values and GSRS and HAMD scores was analyzed too. Results:
      Significant group effects were found in multiple regions: the right pons, the
      left inferior temporal gyrus (ITG)/fusiform, the left superior temporal gyrus
      (STG)/temporal pole, the right inferior frontal gyrus (IFG), the right middle
      occipital gyrus (MOG), the right caudate nucleus, the left posterior cingulate
      cortex/precuneus (pCC/pC), the left postcentral gyrus, the right inferior
      parietal lobule (IPF). Compared with control group, all the two patient groups
      had increased ReHo values in the left pCC/pC, the right IPF, the left postcentral
      gyrus and the left STG/temporal pole; all the two patient groups had decreased
      ReHo values in the right MOG and the right IFG.Compared with non-depression
      group, depression group had increased ReHo values in the right caudate nucleus,
      and decreased ReHo values in the right pons, the left pCC/pC, the right IPF, the
      left postcentral gyrus.Particularly, there was no significant difference in the
      ReHo value in the right caudate nucleus between the control group and the non
      depressed IBS group.In the depression group, significantly positive correlations
      were observed between ReHo values and HAMD scores in the left pCC/pC (r=0.599,
      P=0.011), and significantly positive correlations were observed between ReHo
      values and GSRS in the left postcentral gyrus (r=0.547, P=0.023). Conclusions:
      IBS patients have abnormal ReHo regions in default network and pain regulation
      associated brain area.IBS with depressed patients has its own characteristics in
      the brain regions which related with pain perception and self-regulation.IBS
      could has an abnormal self-regulation of visceral pain, which is associated with
      the occurrence of depression.Depression can aggravate the disorders of pain
      perception and other functions of IBS patients.

PMID- 29374915
TI  - [Clinical and imaging features and etiologic diagnosis value in patients with
      cavernous sinus lesion presenting with ophthalmoplegia].
AB  - Objective: To classify different causes of cavernous sinus lesion in patients
      with ophthalmoplegia and analyze their clinical and imaging features. Methods: We
      confirmed the etiological diagnosis of 137 hospitalized ophthalmoplegia patients
      with cavernous sinus lesion retrospectively from January 2005 to January 2014 in
      the Department of Neurology of Beijing Tongren Hospital.The diagnosis was made
      according to clinical feature, laboratory test, imaging studies and pathology.The
      clinical data of these patients were analyzed and compared among different
      groups. Results: Fifty-one cases (37.2%) were confirmed as inflammatory diseases
      of cavernous sinus, which were the most common cause in 137 patients.Early stage
      pain (OR 5.591, 95%CI 1.703-18.401) and involvement of oculomotor nerve (OR
      4.902, 95%CI 1.015-24.630) were independently associated with inflammatory
      diseases.Forty-three cases (31.3%) were confirmed to have tumor, which was the
      second cause of cavernous sinus lesions, and meningioma was the most common
      tumor.The second branch of trigeminal nerve involvement was independently
      correlated (OR 1.017, 95%CI 1.005-1.071) with tumor.The percentage of male (OR
      3.506, 95%CI 1.362-8.765) was significantly higher in 28 cases (20.4%) with
      cavernous sinus vascular lesions.Cavernous sinus infectious diseases were seen in
      15 cases (10.9%), and fungal infection was the most common, mostly secondary to
      sinus infection. Conclusions: The common causes of cavernous sinus lesion include
      cavernous sinus inflammatory diseases, neoplastic diseases, vascular diseases and
      infectious diseases, and inflammatory diseases is the most commonly seen cause in
      this group of patients.Obvious facial sensory disturbances and the second branch
      of trigeminal nerve involvement are independent associated with tumor.The early
      course of pain and involvement of oculomotor nerve are associated with
      inflammatory diseases.Optimization of MRI examination method can better identify
      the cavernous sinus lesions.

PMID- 29374916
TI  - [Relationship between epicardial adipose tissue and clinical prognosis of
      patients with coronary heart disease after percutaneous coronary intervention].
AB  - Objective: To further evaluate the clinical value of epicardial adipose tissue
      volume (EATV) in predicting the prognosis of coronary heart disease (CHD) after
      percutaneous coronary intervention (PCI). Methods: From July 2013 to July 2016 in
      TEDA International Cardiovascular Disease Hospital, a total of 474 patients
      diagnosed with CHD were included in this study.According to the result of EATV,
      patients were divided into three groups, group A (EATV<=75 ml), group B (75
      ml<EATV<150 ml), and group C (EATV>=150 ml). Then the level of body mass index
      (BMI), hypersensitive c-reactive protein (hs-CRP), interleukin (IL)-6 and tumor
      necrosis factor (TNF)-alpha were tested for all the three groups.All the patients
      were followed up for 1 year for major adverse cardiovascular events (MACE). The
      clinical value of EATV in predicting the occurrence of MACE events was evaluated.
      Results: The BMI, level of hs-CRP, TNF-alpha in group B were higher than group A,
      group C were significantly higher than group B, with statistically significant
      difference across all the comparisons (P<0.05). Spearman correlation analysis
      showed EATV was positively correlated with hs-CRP, IL-6, TNF-alpha (r=0.675
      0.700, P<0.01). The incidence of MACE in the three groups were 8.50% in group C,
      5.26% in group B, 3.13% in group A, and the differences were all significant
      (P<0.01). ROC curve showed the cut-off value of EATV level was 120.39 ml to
      predict MACE (area under cure: 0.751, 95%CI: 0.634-0.868, P<0.01), and the
      sensitivity was 72.7%, the specificity was 61%.EATV>120.39 ml can be used as an
      independent risk factor for predicting the occurrence of MACE. Conclusion: The
      level of EATV is closely related to the occurrence of MACE events, and
      EATV>120.39 ml is an independent risk factor for MACE in patients with CHD after
      PCI.

PMID- 29374917
TI  - [Diagnosis and thoracoscopic treatment for pleuroperitoneal communication
      complicating peritoneal dialysis].
AB  - Objective: To evaluate the safety and efficacy of diagnosis and treatment of
      pleuroperitoneal communication in patients on peritoneal dialysis by computerized
      tomography (CT) peritoneography and thoracoscopic surgery. Methods: The records
      of 8 pleuroperitoneal communication patients treated by thoracoscopic surgery in
      Peking University First Hospital from January 2012 to March 2017 were
      retrospectively reviewed.CT peritoneography was performed before surgical
      treatment. Iopamiro (50 ml?15 g) was mixed with 2 L of peritoneal dialysate
      solution, and then was instilled into the peritoneal cavity through the Tenckhoff
      catheter. After dwelling for 1 hour, CT scan was taken from thorax to upper
      abdomen.The thoracic cavity was filled with sterile saline, and then carbon
      dioxide was inflated to the peritoneal cavity via Tenckhoff catheter.Air bubbles
      leaking from the diaphragmatic defect were identified during thoracoscopic
      operation.Then defect was repaired and pleurodesis was performed. Results: The CT
      value of pleural effusion increased to (155+/-57) HU.Pleuroperitoneal
      communication was clearly diagnosed.The diaphragmatic defects in 5 cases were
      detected and repaired.However, defects in the other 3 cases were not found.The
      mean operative time was (152+/-50) minutes. All patients had uneventful recovery
      and reinstated normal peritoneal dialysis 3 weeks after the operation.The median
      follow-up time was 14.5 months (1-68 months) and no recurrence occurred.
      Conclusions: CT peritoneography could identify pleuroperitoneal communication
      clearly. Thoracoscopic surgery is a safe and reliable method for pleuroperitoneal
      communication and could restore patients to peritoneal dialysis.

PMID- 29374918
TI  - [Comparison of hysteroscopy and curettage in incomplete pregnancy with cesarean
      scar pregnancy].
AB  - Objectives: To evaluate the value of hysteroscopy in the diagnosis and treatment
      of cesarean scar pregnancy (CSP) incomplete abortion. Methods: A total of 42
      patients with incomplete cesarean circumcision from January 2014 to March 2017
      were retrospectively analyzed.Twenty-one patients underwent bilateral uterine
      artery embolization.Twenty patients underwent hysteroscopy Electrocardiose
      resection of pregnancy tissue and coagulation hemostasis, the control group of 22
      patients underwent conventional uterine artery embolization surgery. Results: One
      patient in the study group was changed to laparoscopic surgery.In the control
      group, 2 patients were changed to laparoscopic surgery and 2 patients underwent
      laparotomy.The duration of hospitalization, the amount of postoperative bleeding
      and the duration of bleeding were significantly lower in the study group than in
      the control group.The recovery time of HCG in the study group was significantly
      shorter than that in the control group. Conclusion: Compared with traditional
      uterine artery embolization, hysteroscopic resection of cesarean section scar
      residual tissue less bleeding, higher success rate of surgery, less trauma,
      faster recovery, treatment Cesarean section scar scar pregnancy abortion is the
      ideal method.

PMID- 29374919
TI  - [Expression of IRX1 in cervical cancer and its correlation with clinical stage of
      cervical cancer].
AB  - Objective: To study the expression of IRX1 (Iroquois homeobox gene) in cervical
      cancer and its correlation with clinical stage of cervical cancer. Methods: A
      total of 61 patients with cervical cancer from January 2015 to January 2017 were
      enrolled in this study, of which 15 were classified as phase I of cervical
      cancer, 22 patients were classified as phase II, 19 cases were classified as
      phase III, 5 cases were classified as phase IV followed FIGO staging criteria.The
      expression of IRX1 protein in Hela, C4-1 and Siha cell lines were detected by
      Western blot compared with the normal human cervical epithelial cells
      HCerEpiC.Collected cancerous tissue of cervical cancer as experimental samples,
      the expression of IRX1 mRNA in cancer tissues and paracancerous tissue were
      detected by qPCR.Immunohistochemistry was used to detect the expression of IRX1
      in different stages of cervical cancer, the correlation between IRX1 expression
      and clinical stage was analyzed. Results: The results of Western blot showed that
      IRX1 expression in cervical cancer cells were higher than that in normal cervical
      epithelial cells, and the results of qPCR also showed that the expression of IRX1
      increased with the stage of cancer at the gene level.The difference was
      statistically significant.The expression of IRX1 in the nucleus and cytoplasm
      were detected by immunohistochemistry.Immunohistochemical results showed that the
      higher the stage of cancer was, the higher the expression rate of IRX1 was.
      Conclusion: IRX1 expression is associated with the clinical stage of cervical
      cancer, suggesting that IRX1 may be involved in the development and progression
      of cervical cancer.IRX1 is expected to be a new molecular target for the
      diagnosis and treatment of cervical cancer. This study will provide a new
      theoretical basis for the treatment of cervical cancer.

PMID- 29374920
TI  - [Autophagy and hypoxic ischemic myocardial damage after severe burn].
AB  - It is an important clinical subject to illuminate the mechanisms of myocardial
      damage in the early stage post severe burn in prevention against and treatment of
      burn shock, which may offer a targeted " dynamic support" in the treatment of
      severe burn patients. In recent years, the role of autophagy in hypoxic
      myocardial injury has attracted much attention. Autophagy is a physiological
      phenomenon on intracellular digestion process of long-life proteins and the aging
      and damaged organelles through lysosomal system, and it is essential for
      maintaining the homeostasis of cells. Severe hypoxia/ischemia causes lysosome
      dysfunction, insufficient fusion between autophagosome and lysosome, accumulation
      of autophagosomes, and damaged autophagy flux, thus leading to cell dysfunction
      and cell death. To study the roles of autophagy and explore the potential signals
      in autophagy modulation will provide a new therapeutic target for alleviating
      cardiac dysfunction following severe burn.

PMID- 29374921
TI  - [Effects of cardiac support on delayed resuscitation in extensively burned
      patients with shock].
AB  - Objective: To explore the effects of cardiac support on delayed resuscitation in
      extensively burned patients with shock. Methods: Clinical data of 62 extensively
      burned patients with shock on admission, admitted to the 159th Hospital of PLA
      (hereinafter referred to as our hospital) from January 2012 to January 2017, were
      retrospectively analyzed. They were divided into cardiac support group (n=35) and
      control group (n=27) according to the use of deslanoside and ulinastatin. All
      patients were treated with routine fluid resuscitation based on the formula of
      the Third Military Medical University till post injury hour (PIH) 48. Patients in
      cardiac support group were given slow intravenous injection of deslanoside which
      was added in 20 mL 100 g/L glucose injection with first dose of 0.4 to 0.6 mg,
      0.2 to 0.4 mg per 6 to 8 h, no more than 1.6 mg daily, and slow intravenous
      injection of 1*10(5)U ulinastatin which was added in 100 mL 50 g/L glucose
      injection, once per 12 h. Other treatments of patients in the two groups followed
      the same conventional procedures of our hospital. The following data of the two
      groups of patients were collected. (1) The data of urine volume per hour within
      PIH 48, heart rate, mean arterial pressure (MAP), central venous pressure (CVP),
      blood lactic acid, base excess, hematocrit, and albumin at PIH 48 were recorded.
      (2) The input volumes of electrolyte, colloid within the first and second 24
      hours post burn and the total fluid input volumes within PIH 48 were recorded.
      (3) The data of creatine kinase, creatine kinase isoenzyme-MB, lactate
      dehydrogenase, total bile acid, alanine aminotransferase, aspartate
      aminotransferase, beta(2)-microglobulin, urea nitrogen, and creatinine at PIH 48
      were recorded. (4) The complications including cardiac failure, pulmonary edema,
      pleural effusion, seroperitoneum, renal failure, sepsis, and death were also
      recorded. Data were processed with independent sample ttest, Fisher's exact test,
      Pearson chi-square test, or continuous correction chi-square test. Results: (1)
      There were no statistically significant differences in urine volume within PIH
      48, heart rate, MAP, CVP, hematocrit, or albumin at PIH 48 between the patients
      of two groups (t=0.150, 0.488, 0.805, 0.562, 1.742, 0.696, P>0.05). While the
      levels of blood lactic acid and base excess were respectively (4.2+/-2.2) and (
      4.3+/-2.0) mmol/L in patients of cardiac support group, which were significantly
      better than (5.9+/-1.7) and (-6.0+/-3.1) mmol/L in patients of control group
      (t=3.249, 2.480, P<0.05 or P<0.01). (2) There was no statistically significant
      difference in input volume of colloid within the first 24 hours post burn between
      the patients of two groups (t=0.642, P>0.05). The input volume of electrolyte
      within the first 24 hours post burn, the input volumes of electrolyte and colloid
      within the second 24 hours post burn, and the total fluid input volume within PIH
      48 of patients in cardiac support group were significantly less than those in
      control group (t=2.703, 4.223, 3.437, 2.515, P<0.05 or P<0.01). (3) The levels of
      creatine kinase, creatine kinase isoenzyme-MB, lactate dehydrogenase, total bile
      acid, alanine aminotransferase, aspartate aminotransferase, beta(2)
      microglobulin, urea nitrogen, and creatinine of patients in cardiac support group
      at PIH 48 were significantly lower than those in control group (t=3.066, 3.963,
      3.225, 2.943, 2.431, 3.084, 4.052, 2.915, 3.353, P<0.05 or P<0.01). (4) The
      occurrences of pleural effusion and seroperitoneum and mortality of patients in
      cardiac support group were significantly lower than those in control group
      (chi(2)=5.514, 6.984, 4.798, P<0.05 or P<0.01). There were no statistically
      significant differences in cardiac failure, pulmonary edema, renal failure, and
      sepsis between the patients of two groups [chi(2)=1.314 (sepsis), P>0.05].
      Conclusions: The cardiotonic and cardiac protection treatments in delayed
      resuscitation of extensively burned patients with shock contribute to improving
      the cellular anonic metabolism, reducing the volume of fluid resuscitation, and
      mitigating the ischemic and hypoxic damage to organs, so as to lay foundation for
      decreasing further complication incidences and mortality.

PMID- 29374922
TI  - [Effects of application of pulse contour cardiac output monitoring technology in
      early treatment of patients with large area burns].
AB  - Objective: To analyze the changes and relationship of early hemodynamic indexes
      of patients with large area burns monitored by pulse contour cardiac output
      (PiCCO) monitoring technology, so as to assess the guiding value of this
      technology in the treatment of patients with large area burns during shock
      period. Methods: Eighteen patients with large area burns, confirming to the study
      criteria, were admitted to our unit from May 2016 to May 2017. Pulse contour
      cardiac output index (PCCI), systemic vascular resistance index (SVRI), global
      end-diastolic volume index (GEDVI), and extravascular lung water index (EVLWI) of
      patients were monitored by PiCCO instrument from admission to post injury day
      (PID) 7, and they were calibrated and recorded once every four hours. The fluid
      infusion coefficients of patients at the first and second 24 hours post injury
      were calculated. The blood lactic acid values of patients from PID 1 to 7 were
      also recorded. The correlations among PCCI, SVRI, and GEDVI as well as the
      correlation between SVRI and blood lactic acid of these 18 patients were
      analyzed. Prognosis of patients were recorded. Data were processed with one-way
      analysis of variance, single sample ttest and Bonferroni correction, Pearson
      correlation analysis, and Spearman rank correlation analysis. Results: (1) There
      was statistically significant difference in PCCI value of patients from post
      injury hour (PIH) 4 to 168 (F=7.428, P<0.01). The PCCI values of patients at PIH
      4, 8, 12, 16, 20, and 24 were (2.4+/-0.9), (2.6+/-1.2), (2.2+/-0.6), (2.6+/-0.7),
      (2.8+/-0.6), and (2.7+/-0.7) L.min(-1).m(-2,) respectively, and they were
      significantly lower than the normal value 4 L.min(-1).m(-2)(t=-3.143, -3.251, 
      11.511, -8.889, -6.735, -6.976, P<0.05 or P<0.01). At PIH 76, 80, 84, 88, 92, and
      96, the PCCI values of patients were (4.9+/-1.5), (5.7+/-2.0), (5.9+/-1.7),
      (5.5+/-1.3), (5.3+/-1.1), and (4.9+/-1.4) L.min(-1).m(-2,) respectively, and they
      were significantly higher than the normal value (t=2.277, 3.142, 4.050, 4.111,
      4.128, 2.423, P<0.05 or P<0.01). The PCCI values of patients at other time points
      were close to normal value (P>0.05). (2) There was statistically significant
      difference in SVRI value of patients from PIH 4 to 168 (F=7.863, P<0.01). The
      SVRI values of patients at PIH 12, 16, 20, 24, and 28 were (2 298+/-747), (2
      581+/-498), (2 705+/-780), (2 773+/-669), and (3 109+/-1 215) dyn.s.cm(-5).m(2,)
      respectively, and they were significantly higher than the normal value 2 050
      dyn.s.cm(-5).m(2)(t=0.878, 3.370, 2.519, 3.747, 3.144, P<0.05 or P<0.01). At PIH
      4, 8, 72, 76, 80, 84, 88, 92, and 96, the SVRI values of patients were (1 632+/
      129), (2 012+/-896), (1 381+/-503), (1 180+/-378), (1 259+/-400), (1 376+/-483),
      (1 329+/-385), (1 410+/-370), and (1 346+/-346) dyn.s.cm(-5).m(2,) respectively,
      and they were significantly lower than the normal value (t=-4.593, -0.112, 
      5.157, -8.905, -7.914, -5.226, -6.756, -6.233, -7.038, P<0.01). The SVRI values
      of patients at other time points were close to normal value (P>0.05). (3) There
      was no statistically significant difference in the GEDVI values of patients from
      PIH 4 to 168 (F=0.704, P>0.05). The GEDVI values of patients at PIH 8, 12, 16,
      20, and 24 were significantly lower than normal value (t=-3.112, -3.554, -2.969, 
      2.450, -2.476, P<0.05). The GEDVI values of patients at other time points were
      close to normal value (P>0.05). (4) There was statistically significant
      difference in EVLWI value of patients from PIH 4 to 168 (F=1.859, P<0.01). The
      EVLWI values of patients at PIH 16, 20, 24, 28, 32, 36, and 40 were significantly
      higher than normal value (t=4.386, 3.335, 6.363, 4.391, 7.513, 5.392, 5.642,
      P<0.01). The EVLWI values of patients at other time points were close to normal
      value (P>0.05). (5) The fluid infusion coefficients of patients at the first and
      second 24 hours post injury were 1.90 and 1.39, respectively. The blood lactic
      acid values of patients from PID 1 to 7 were 7.99, 5.21, 4.57, 4.26, 2.54, 3.13,
      and 3.20 mmol/L, respectively, showing a declined tendency. (6) There was obvious
      negative correlation between PCCI and SVRI (r=-0.528, P<0.01). There was obvious
      positive correlation between GEDVI and PCCI (r=0.577, P<0.01). There was no
      obvious correlation between GEDVI and SVRI (r=0.081, P>0.05). There was obvious
      positive correlation between blood lactic acid and SVRI (r=0.878, P<0.01). (7)
      All patients were cured except the one who abandoned treatment. Conclusions:
      PiCCO monitoring technology can monitor the changes of early hemodynamic indexes
      and volume of burn patients dynamically, continuously, and conveniently, and
      provide valuable reference for early-stage comprehensive treatment like anti
      shock of patients with large area burns.

PMID- 29374924
TI  - [Advances in the research of application of urine output monitoring in prevention
      and treatment of burn shock].
AB  - Fluid therapy is a crucial treatment for patients with extensive burn, which
      affects patients'prognosis directly. Accurate urine output measurement plays an
      irreplaceable role in guiding fluid resuscitation in clinic. As one of the best
      indexes in traditional burn resuscitation, urine output comprehensively reflects
      systemic circulation. However, it doesn't fully reflect all the specific chapters
      of microcirculation and systemic circulation and deficient cellular oxygen
      metabolism exactly. We need to use urine output combined with other shock
      parameters to ensure adequate fluid replacement. Currently, the most common way
      of urine output monitoring is manual measurement. The article reviews the
      application of urine output monitoring in guiding fluid resuscitation of burn
      shock.

PMID- 29374923
TI  - [Effects of microRNA-34a on regulating silent information regulator 1 and
      influence of the factor on myocardial damage of rats with severe burns at early
      stage].
AB  - Objective: To explore the effects of microRNA-34a on regulating silent
      information regulator 1 (SIRT1) and influence of SIRT1 on myocardial damage of
      rats with severe burns at early stage. Methods: (1) Twenty-four Sprague-Dawley
      (SD) rats were divided into sham injury (SI) group, simple burns (SB) group and
      SIRT1 agonist (SA) group according to the random number table (the same grouping
      method below), with 8 rats in each group. Rats in groups SB and SA were inflicted
      with 30% total body surface area full-thickness scald (hereinafter referred to as
      burns) on the back, and rats in group SI were sham injuried on the back.
      Immediately after injury, rats in groups SI and SB were intraperitoneally
      injected with normal saline of 50 mL/kg, and rats in group SA were
      intraperitoneally injected with normal saline of 50 mL/kg and 1 mg/mL resveratrol
      of 50 mg/kg. At 6 h post injury, abdominal aortic blood was collected to make
      serum and myocardial tissue of rats was collected. (2) Myocardial cells of twelve
      neonatal SD rats were collected and divided into microRNA-34a mimic control (MMC)
      group, microRNA-34a mimic (MM) group, microRNA-34a inhibitor control (MIC) group,
      and microRNA-34a inhibitor (MI) group, which were respectively transfected with
      gene sequences of mimic control, mimic, inhibitor control, and inhibitor of
      microRNA-34a. The microRNA-34a expression level and protein expression level of
      SIRT1 in myocardial cells were respectively detected by real-time fluorescence
      quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western
      blotting. Another batch of myocardial cells were divided into microRNA-34a
      inhibitor control+ burn serum (MCB) group, microRNA-34a inhibitor+ burn serum
      (MB) group, and microRNA-34a inhibitor+ burn serum + EX527 (MBE) group.
      Myocardial cells in group MCB were transfected with gene sequence of inhibitor
      control, and myocardial cells in the later groups were transfected with gene
      sequence of inhibitor of microRNA-34a. After transfection of 48 h, myocardial
      cells in group MBE were cultured in Dulbecco's modified Eagle's medium (DMEM)
      solution for 6 hours, with serum in group SB of volume fraction of 10% and final
      amount-of-substance concentration of 1 mol/L, and myocardial cells in the other 2
      groups were cultured in DMEM solution with serum from rats of group SB of volume
      fraction of 10%. The protein expression levels of myocardial cells of SIRT1,
      cleaved-caspase-3, and Bax were detected by Western blotting. (3) Myocardial
      tissue from (1) was collected to detect expression levels of microRNA-34a and
      mRNA of SIRT1 in groups SI and SB by real-time fluorescence quantitative RT-PCR.
      Morphology of myocardial tissue of rats in groups SI, SB, and SA was observed
      with biological image navigator. The mRNA expression levels of interleukin 1beta
      (IL-1beta) and tumor necrosis factor (TNF-alpha) of rats in groups SI, SB, and SA
      were detected by real-time fluorescence quantitative RT-PCR. The expression
      levels of cleaved-caspase-3, and Bax of myocardial tissue of rats in groups SI,
      SB, and SA were detected by Western blotting. Data were processed with one-way
      analysis of variance and least-significant difference test. Results: (1) After
      transfection of 48 h, the expression level of microRNA-34a of myocardial cells in
      group MM was 4.67+/-0.92, significantly higher than 1.03+/-0.04 in group MMC
      (P<0.01); the protein expression level of SIRT1 of myocardial cells in group MM
      was 0.35+/-0.06, significantly lower than 1.12+/-0.11 in group MMC (P<0.01).
      After transfection of 48 h, the expression level of microRNA-34a of myocardial
      cells in group MI was 0.26+/-0.07, significantly lower than 1.33+/-0.07 in group
      MIC (P<0.01); the protein expression level of SIRT1 of myocardial cells in group
      MIC was 1.12+/-0.16, significantly lower than 1.74+/-0.34 in group MI (P<0.01).
      At 6 h after culture, compared with those in group MCB, the SIRT1 protein
      expression level of myocardial cells in group MB was significantly increased
      (P<0.05), while cleaved-caspase-3 and Bax protein expression levels of myocardial
      cells in group MB were significantly decreased (P<0.05). Compared with those in
      group MB, the SIRT1 protein expression level of myocardial cells in group MBE was
      with no significantly statistical difference (P>0.05), and cleaved-caspase-3 and
      Bax protein expression levels were significantly increased (P<0.05). (2) At 6 h
      post injury, compared with that in group SI, the microRNA-34a expression level of
      myocardial tissue in group SB was significantly increased (P<0.01), and the mRNA
      expression level of SIRT1 of myocardial tissue in group SB was significantly
      decreased (P<0.01). At 6 h post injury, myocardial cells in group SI arranged
      neatly with normal nucleus and no inflammatory cells infiltration; myocardial
      cells in group SB arranged disorderly, with no abnormal nucleus, and obvious
      inflammatory cells infiltration; myocardial cells in group SA arranged neatly,
      with normal nucleus and little inflammatory cells infiltration. At 6 h post
      injury, compared with those in group SB, the mRNA expression levels of IL-1beta
      and TNF-alpha, and the protein expression levels of cleaved-caspase-3 and Bax of
      myocardial tissue in groups SI and SA were significantly decreased (P<0.01).
      Conclusions: The microRNA-34a expression level of myocardial tissue of rats with
      severe burns at early stage increases, which decreases the expression level of
      SIRT1, and increases the expression levels of IL-1beta, TNF-alpha, cleaved
      caspase-3 and Bax, leading to obvious myocardial damage. Activation of SIRT1 can
      alleviate myocardial damage of rats with severe burns at early stage through
      decreasing expression levels of IL-1beta, TNF-alpha, cleaved-caspase-3, and Bax.

PMID- 29374925
TI  - [Influences of ulinastatin on acute lung injury and time phase changes of
      coagulation parameters in rats with burn-blast combined injuries].
AB  - Objective: To explore the influences of ulinastatin on acute lung injury and time
      phase changes of coagulation parameters in rats with severe burn-blast combined
      injuries. Methods: One hundred and ninety-two Sprague-Dawley rats were divided
      into pure burn-blast combined injury group, ulinastatin+ burn-blast combined
      injury group, and sham injury group according to the random number table, with 64
      rats in each group. Two groups of rats with combined burn-blast injuries were
      inflicted with moderate blast injuries with the newly self-made explosive device.
      Then the rats were inflicted with 25% total body surface area full-thickness
      scald (hereinafter referred to as burn) on the back by immersing in 94 C hot
      water for 12 s. Rats in sham injury group were sham injured on the back by
      immersing in 37 C warm water for 12 s. Immediately after injury, rats in the
      three groups were intraperitoneally injected with Ringer's lactate solution (40
      mL/kg), meanwhile rats in ulinastatin+ burn-blast combined injury group were
      intraperitoneally injected with ulinastatin (4*10(4)U/kg), once every 12 hours,
      until post injury hour (PIH) 72. Before injury, at PIH 3, 6, 12, 24, 48, 72, and
      on post injury day (PID) 7, 8 rats in each group were selected to harvest
      abdominal aortic blood samples to detect plasma levels of activated partial
      thromboplastin time (APTT), prothrombin time (PT), fibrinogen, D-dimer,
      antithrombin III (AT-III), and alpha2-antiplasmin (alpha2-AP). At PIH 24, three
      rats in each group which were used in detection of coagulation parameters were
      sacrificed to observe lung injury. At PIH 72, three rats in each group were
      sacrificed for histopathological observation of lung. Data were processed with
      analysis of variance of factorial design and least-significant difference test.
      Results: (1) Compared with those of rats in sham injury group, APTT of rats in
      pure burn-blast combined injury group significantly prolonged at PIH 72 and on
      PID 7 (P<0.05 or P<0.01). PT significantly prolonged at PIH 3 and 72 and
      significantly shortened at PIH 6 (P<0.05 or P<0.01) . Fibrinogen level
      significantly increased from PIH 12 to PID 7 (P<0.01). AT-III level significantly
      decreased at PIH 6 and 12 (P<0.01), and alpha2-AP level significantly decreased
      at PIH 6 and significantly increased from PIH 24 to 72 (P<0.01). Compared with
      those of rats in pure burn-blast combined injury group, APTT of rats in
      ulinastatin+ burn-blast combined injury group significantly prolonged at PIH 3
      and 6 (P<0.01) while PT significantly shortened at PIH 3, 12, and 72 (P<0.05 or
      P<0.01). Fibrinogen level significantly decreased at PIH 6 and 12 and
      significantly increased at PIH 72 (P<0.05 or P<0.01). AT-III level significantly
      increased at PIH 3, 12, 48, and 72 (P<0.05 or P<0.01), and alpha2-AP level
      significantly decreased from PIH 12 to 72 (P<0.05 or P<0.01). D-dimer level of
      rats in sham injury group, pure burn-blast combined injury group, and
      ulinastatin+ burn-blast combined injury group were respectively (0.084+/-0.013),
      (0.115+/-0.015), (0.158+/-0.022), (0.099+/-0.011), (0.099+/-0.012), (0.089+/
      0.011), (0.124+/-0.014), and (0.116+/-0.018) MUg/mL, (0.064+/-0.033), (0.114+/
      0.016), (0.135+/-0.009), (0.060+/-0.008), (0.104+/-0.010), (0.124+/-0.020),
      (0.180+/-0.036), and (0.201+/-0.032) MUg/mL, (0.074+/-0.013), (0.084+/-0.035),
      (0.101+/-0.050), (0.091+/-0.046), (0.096+/-0.034), (0.044+/-0.019), (0.106+/
      0.049), and (0.118+/-0.047) MUg/mL. Compared with that of rats in sham injury
      group, D-dimer level significantly decreased at PIH 6 and 12 and significantly
      increased from PIH 48 to PID 7 (P<0.05 or P<0.01). Compared with that of rats in
      pure burn-blast combined injury group, D-dimer level of rats in ulinastatin+ burn
      blast combined injury group significantly decreased at PIH 3, 48, and 72, and on
      PID 7 (P<0.05 or P<0.01). (2) At PIH 24, there was a large amount of light red
      effusion in the thoracic cavity, and both lung lobes were hyperemic and edematous
      with a small amount of blood clots in the left and middle lobe of rats in pure
      burn-blast combined injury group. There was a small amount of yellowish effusion
      in the thoracic cavity of rats in ulinastatin+ burn-blast combined injury group,
      and the degree of hyperemic and edematous of bilateral lobes was lighter compared
      with rats in pure burn-blast combined injury group with no clot in the left lobe.
      No congestion, edema, or bleeding was observed in lungs of rats in sham injury
      group. (3) At PIH 72, disorganized alveolar structure, collapsed alveolar cavity,
      edematous and thickening pulmonary interstitium, infiltration of a large amount
      of inflammatory cells, obvious rupture of alveolar septum, and hyaline thrombus
      were observed in lungs of rats in pure burn-blast combined injury group.
      Significantly improved alveolar structure, less collapsed alveolar cavity,
      improved edematous pulmonary interstitium, less infiltration of inflammatory
      cells, rupture of alveolar septum, and no thrombus were observed in lungs of rats
      in ulinastatin+ burn-blast combined injury group. The lung tissue had a well
      filled alveolar cavity with no interstitial edema or infiltration of inflammatory
      cells and no thrombosis in lungs of rats in sham injury group. Conclusions:
      Ulinastatin has positive therapeutic effects on acute lung injury in rats with
      severe burn-blast combined injuries through its good regulating effects on
      coagulation and fibrinolytic disorders caused by burn-blast combined injuries.

PMID- 29374926
TI  - [Effects of early enteral nutrition in the treatment of patients with severe
      burns].
AB  - Objective: To investigate the effects of early enteral nutrition (EEN) in the
      treatment of patients with severe burns. Methods: Medical records of 52 patients
      with severe burns hospitalized in the three affiliations of authors from August
      to September in 2014 were retrospectively analyzed and divided into EEN group
      (n=28) and non-early enteral nutrition (NEEN) group (n=24) according to the
      initiation time of enteral nutrition. On the basis of routine treatment, enteral
      nutrition was given to patients in group EEN within post injury day (POD) 3,
      while enteral nutrition was given to patients in group NEEN after POD 3. The
      following items were compared between patients of the two groups, such as the
      ratio of enteral nutrition intake to total energy intake, the ratio of parenteral
      nutrition intake to total energy intake, the ratio of total energy intake to
      energy target on POD 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28, the levels of
      prealbumin, serum creatinine, blood urea nitrogen, total bilirubin, direct
      bilirubin, and Acute Physiology and Chronic Health Evaluation II (APACHE II)
      score on POD 1, 3, 7, 14, and 28, the first operation time, the number of
      operations, and the frequencies of abdominal distension, diarrhea, vomiting,
      aspiration, catheter blockage, and low blood sugar within POD 28. Data were
      processed with chi(2)test, ttest, Wilcoxon rank sum test, and Bonferroni
      correction. Results: (1) The ratio of parenteral nutrition intake to total energy
      intake of patients in group EEN on POD 1 was obviously lower than that in group
      NEEN (Z=2.078, P<0.05). The ratio of enteral nutrition intake to total energy
      intake and the ratio of total energy intake to energy target of patients in group
      EEN on POD 2 and 3 were obviously higher than those in group NEEN (Z=5.766,
      6.404, t=4.907, 6.378, P<0.01). The ratio of total energy intake to energy target
      of patients in group EEN was obviously lower than that in group NEEN on POD 4, 5,
      6, and 7 (t=4.635, 2.547, 3.751, 5.373, P<0.05 or P<0.01). On POD 2, 4, 5, 14,
      21, and 28, the ratio of enteral nutrition intake to total energy intake of
      patients in group EEN was obviously higher than the ratio of parenteral nutrition
      intake to total energy intake within the same group (Z=5.326, 2.046, 2.129,
      4.118, 3.174, 3.963, P<0.05 or P<0.01). In group NEEN, the ratio of enteral
      nutrition to total energy intake of patients on POD 1, 2, and 3 was obviously
      lower than the ratio of parenteral nutrition intake to total energy intake within
      the same group (Z=2.591, 2.591, 3.293, P<0.05 or P<0.01), while the ratio of
      enteral nutrition to total energy intake of patients on POD 14, 21, 28 was
      obviously higher than the ratio of parenteral nutrition intake to total energy
      intake within the same group (Z=2.529, 3.173, 3.133, P<0.05 or P<0.01). (2) The
      prealbumin levels of patients in the two groups were close on POD 1, 3, 7, and 14
      (t=1.983, 0.093, 0.832, 1.475, P>0.05). On POD 28, the prealbumin level of
      patients in group EEN was obviously higher than that in group NEEN (t=3.163,
      P<0.05). The levels of serum creatinine, blood urea nitrogen, total bilirubin,
      and direct bilirubin of patients in the two groups at all time points post injury
      were close (Z=1.340, 0.547, 0.245, 0.387, 0.009, 1.170, 0.340, 1.491, 0.274,
      1.953, 0.527, 0.789, 0.474, 1.156, 0.482, 0.268, 0.190, 0.116, 1.194, 0.431,
      P>0.05). (3) The APACHE II scores of patients in group EEN were (22.5+/-3.1) and
      (15.6+/-3.8) points respectively on POD 1 and 3, which were close to (23.6+/-3.0)
      and (17.6+/-4.2) points of patients in group NEEN (t=1.352, 1.733, P>0.05). The
      APACHE II scores of patients in group EEN on POD 7, 14, and 28 were (13.6+/-3.6),
      (13.8+/-4.1), and (15.5+/-4.1) points, respectively, which were obviously lower
      than (18.5+/-3.9), (19.5+/-4.2) and (20.8+/-3.8) points of patients in group NEEN
      (t=4.677, 4.843, 4.792, P<0.05). (4) Within POD 28, the time of the first
      operation, the number of operations, and the frequencies of abdominal distension,
      diarrhea, vomiting, aspiration, catheter blockage and hypoglycemia were similar
      between patients of the two groups (t=0.684, 0.782, Z=0.161, 1.751, 0.525, 0.764,
      0.190, 0.199, P>0.05). Conclusions: EEN in the treatment of patients with severe
      burns potentially increases the energy intake at early stage and improves APACHE
      II score and prealbumin level on POD 28, without increasing frequencies of
      adverse reactions.

PMID- 29374927
TI  - [Advances in the research of function of Merkel cells in tactile formation of
      skin].
AB  - Skin is the largest sense organ of human, with many mechanoreceptor cells under
      epidermis or dermis of skin and Merkel cell is one of them. It has been confirmed
      that Merkel cells play an important role in the process of mechanical
      transmission of mammalian soft tactile stimulation. Researches showed that Merkel
      cells had close relation to tactile formation and functioned by Merkel cell
      neurite complexes and ion channels Piezo2. This article reviews Merkel cells and
      the function, problem and prospect of Merkel cells in tactile formation.

PMID- 29374928
TI  - [Advances in the research of relationship between CD26 and hypertrophic scar and
      keloid].
AB  - In recent years, researchers have found that CD26 (dipeptidyl peptidase 4) is
      closely related to the formation and development of many fibrotic diseases.
      Hypertrophic scar, keloid, and other skin fibrosis diseases are major problems
      nowadays, which may affect the patient's appearance and cause joints deformity
      and dysfunction due to scar contracture. This article briefly reviews the
      relationship between CD26 and hypertrophic scar and keloid to provide new
      insights into the treatment of skin fibrotic diseases.

PMID- 29374929
TI  - [Advances in the research of zinc deficiency and zinc supplementation treatment
      in patients with severe burns].
AB  - Zinc is one of the essential trace elements in human body, which plays an
      important role in regulating acute inflammatory response, glucose metabolism,
      anti-oxidation, immune and gastrointestinal function of patients with severe
      burns. Patients with severe burns may suffer from zinc deficiency because of
      insufficient amount of zinc intake from the diet and a large amount of zinc lose
      through wounds and urine. Zinc deficiency may affect their wound healing process
      and prognosis. This article reviews the characteristics of zinc metabolism in
      patients with severe burns through dynamic monitoring the plasma and urinary
      concentration of zinc. An adequate dosage of zinc supplemented to patients with
      severe burns by an appropriate method can increase the level of zinc in plasma
      and skin tissue and improve wound healing, as well as reduce the infection rates
      and mortality. At the same time, it is important to observe the symptoms and
      signs of nausea, dizziness, leukopenia and arrhythmia in patients with severe
      burns after supplementing excessive zinc.

PMID- 29374930
TI  - [Strength our efforts on innovation of medical science and technology to promote
      the development of cardiovascular cause in China].

PMID- 29374931
TI  - [Deepen our thoughts on the prevention of cardiovascular disease and actively
      contribute to the earlier appearance of the turning point noting the reduced
      prevalence of cardiovascular diseases].

PMID- 29374932
TI  - [Value of selective thrombus aspiration during primary percutaneous coronary
      intervention in patients with acute ST-segment elevation myocardial infarction].

PMID- 29374933
TI  - [Chinese guidelines for the prevention of cardiovascular diseases(2017)].

PMID- 29374934
TI  - [Status of intra-aortic balloon pump application and related factors in Chinese
      patients with acute myocardial infarction].
AB  - Objective: To investigate the current status of application of intra-aortic
      balloon pump(IABP) and analyze the factors which might impact the application of
      IABP in patients with acute myocardial infarction complicated with cardiac shock
      in China. Methods: In China Acute Myocardial Infarction (CAMI) Registry,a
      nationwide, multicenter(107 hospitals), prospective study, 26 592 patients with
      acute myocardial infarction were enrolled consecutively between January 1, 2013
      and September 30, 2014. After excluding of 30 cases due to missing important
      data,26 562 cases were analyzed.The application status of IABP was analyzed and
      multivariate logistic regression analysis was performed to determine the factors
      related to IABP application. Results: A total of 785(3.0%) patients with acute
      myocardial infarction received IABP implantation, and 381(49.9%) patients
      belonged to preventive application of IABP before primary percutaneous coronary
      intervention,and 6(0.8%) patients were complicated with mechanical
      complications.There were 118(15.0%) patients with cardiac shock received IABP
      implantation, which accounted for 12.0%(118/984) of all patients with cardiac
      shock.Multivariate logistic regression analysis showed that the clinical
      independent factors of the decision of IABP insertion included dyslipidemia
      (OR=2.858, 95%CI 1.397-5.846, P=0.004),left ventricular ejection fraction
      (OR=0.977, 95%CI 0.961-0.994, P=0.009),usage of dopamine (OR=2.817, 95%CI 1.495
      5.308, P=0.001), left main disease (OR=2.817, 95%CI 1.495-5.308, P=0.001), GRACE
      score (OR=1.006, 95%CI 1.000-1.011, P=0.034), receiving primary percutaneous
      coronary intervention (OR=4.508, 95%CI 1.673-12.146, P=0.003), teritiary
      hospitals (OR=2.562, 95%CI 1.498-4.384, P=0.001), and higher education of the
      patients (OR=2.183, 95%CI 1.056-4.509, P=0.016). Conclusions: Among the Chinese
      acute myocardial infarction patients who received IABP implantation, nearly half
      application of IABP are preventive implantation before primary percutaneous
      coronary intervention. Only a few patients complicated with cardiac shock
      received IABP insertion. The clinical conditions, grade of hospitals, degree of
      education impact the decision of IABP insertion for the patients with acute
      myocardial infarction. Clinical Trial Registry National Institutes of Health,
      NCT018746.

PMID- 29374935
TI  - [Therapeutic efficacy of paclitaxel-coated balloon for de novo coronary lesions
      with diameters larger than 2.8 mm].
AB  - Objective: To evaluate the efficacy of paclitaxel-coated balloon for de novo
      coronary lesions with diameters >= 2.8 mm. Methods: This prospective study
      included 215 consecutive patients with 238 de novo lesions, who received
      paclitaxel-coated balloon angioplasty in Beijing Hospital from May 2014 to June
      2016. According to the reference vessel diameter, the patients were divided into
      large vessel disease (LVD) group (reference vessel diameter>=2.8 mm, 85 patients
      and 90 lesions) and small vessel disease (SVD) group (reference vessel
      diameter<2.8 mm, 130 patients and 148 lesions). Clinical characteristics,
      interventional procedures and major adverse cardiovascular events (includingall
      cause mortality, non-fatal myocardial infarction and target lesion
      revascularization) after procedure were compared between the 2 groups. Results:
      (1)Patients in LVD group were younger than SVD group ((60.1+/-11.1) years old vs.
      (65.0+/-10.6) years old, P<0.01), and less patients had diabetes (24.7% (21/85)
      vs. 43.1%(56/130), P<0.01).(2)Prevalence of three-vessel disease (35.5%(30/85)
      vs. 53.6%(67/130), P<0.05) and complex lesions (type B2/C,34.4% (31/90) vs.
      50.0%(74/148), P<0.05) were significantly lower in LVD group than in SVD
      group.(3) During pre-dilation, the rate with plain balloons use was significantly
      higher in SVD group than in LVD group(76.4%(113/148) vs. 58.9%(53/90), P<0.01),
      while the proportion of additional use of non-compliant balloons was
      significantly higher in LVD groupthan in SVD group(20.0% (18/90) vs. 3.4% (5/148)
      , P<0.01). The ratio of paclitaxel-coated balloon diameter/RVD was significantly
      lower (0.87+/-0.12 vs. 0.96+/-0.15, P<0.01) and the duration of dilationwas
      significantly shorter ((41.5+/-9.5) seconds vs. (45.1+/-9.1) seconds, P<0.01) in
      LVD group than those in SVD group. Each group had 1 failure case that was bailout
      stented with drug-eluting stents. The success rate of paclitaxel-coated balloon
      treatment was similar in LVD group and SVD group (98.9% (89/90) vs.
      99.3%(147/148), P>0.05).(4) At the fourth day of procedure, there was 1 acute
      myocardial infarction requiring emergent target lesion revascularization in SVD
      group. No major adverse cardiovascular event was observed in LVD group during
      hospitalization. Forty-two patients with 53 lesions, including 27 LVD lesions and
      26 SVD lesions,underwent coronary angiography at (9.4+/-4.6) months after
      paclitaxel-coated balloon intervention. The quantitative coronary angiography
      analysis showed that minimal lumen diameter significantlyincreased during follow
      up than that of post-procedurein SVD group ((1.71+/-0.36)mm vs. (1.52+/-0.30)mm,
      P<0.05) , while in LVD group the minimal lumen diameter was similar between
      during follow-up and post-procedure ((2.35+/-0.48)mm vs. (2.19+/-0.34)mm,
      P>0.05). Major adverse cardiovascular event rate was 0 in LVD group and
      2.3%(3/130) in SVD group (P>0.05) during follow up. No death was observed in this
      patient cohort. Conclusion: Treatment with paclitaxel-coated balloon for de novo
      coronary lesions with diameters>=2.8 mm is safe and effective.

PMID- 29374936
TI  - [Feasibility and safety of paclitaxel-eluting balloon for the treatment of de
      novo coronary lesions].
AB  - Objective: To evaluate the safety and feasibility of treating de novo coronary
      lesions with paclitaxel-eluting balloon. Methods: This is a retrospective study,
      which enrolled 76 patients with 80 de novo coronary lesions treated with
      paclitaxel-eluting balloons(<30% residual stenosis and there was no blood flow
      limited dissection after pretreatment) from April 2015 to November 2016 in
      Guangdong general hospital. The data of basic characteristics,procedures,devices
      and follow-up information were retrieved and analyzed. The primary endpoint was
      the composite of cardiac death, recurrent myocardial infarction and target lesion
      revascularization. Results: (1)The age was (63.3+/-10.3) years. There were
      68.4%(52/76) acute coronary syndrome patients, prevalence of type 2 diabetes was
      36.8%(28/76), and 64.5%(49/76)patients with at least one high bleeding risk.
      (2)The lesion length was (17.4+/-7.6)mm, and the stenosis was (88.1+/-8.2)%.The
      reference vessel diameter>=2.75 mm accounted for 51.2% (41/80), and bifurcation
      stenosis accounted for 67.5%(54/80). (3)53.7%(43/80) lesions were pretreated with
      scoring balloon to optimize plaque modification. The paclitaxel-eluting balloon
      length and diameter were (22.3+/-5.5)mm and (2.74+/-0.52)mm.The residual stenosis
      was (12.3+/-10.3)%. Procedural success was 88.8%(71/80).Bail-out stenting rate
      was 5.0%(4/80). (4)The median follow-up duration was 12(6, 25) months. Primary
      endpoint occurred in 3 cases (3.9%), including 2 cardiac deaths(1 patient died of
      recurrent myocardial infarction, and 1 patient died of acute heart failure
      induced by severe mitral insufficiency), and one patient receivedtarget lesion
      revascularization. Conclusion: In case of no more than 30% residual stenosis and
      no blood flow limited dissection after lesion pretreatment,it is safe and
      feasible to treat de novo coronary lesionsusing paclitaxel-eluting balloon.

PMID- 29374937
TI  - [Optical coherence tomographic analysis of in-stent neoatherosclerosis in lesions
      with restenosis after drug-eluting stent implantation].
AB  - Objective: To explore the imaging characteristics and related influencing factors
      of in-stent neoatherosclerosis (ISNA) in patients with restenosis after drug
      eluting stent(DES) implantation with optical coherence tomography(OCT). Methods:
      A total of 25 cases of coronary heart disease patients(DES placement time >=8
      months) with coronary artery angiography showing DES in-stent restenosis (ISR) in
      Zunyi medical college affiliated hospital from July 2013 to December 2015 were
      included in this study and patient's data were retrospectively analyzed.In these
      patients with ISR, OCT images were acquired before percutaneous coronary
      intervention. Patients were divided into the ISNA group (12 patients and 12
      lesions) and non-ISNA group(13 patients and 13 lesions) according to the result
      of OCT. ISNA on OCT was defined as neointima formation with the presence of
      lipids or calcification. Results: (1) The incidence of chronic kidney disease and
      increased low-density lipoprotein cholesterol level in ISNA group were
      significant higher than that in non-ISNA group(all P<0.05). The stent
      implantation time in ISNA group was longer than that in the non-ISNA
      group(53.0(14.0, 81.0) months vs. 15.0(8.5, 32.5) months, P<0.01). In addition,
      clinical manifestation of acute coronary syndrome was present in 8 out of 12
      patientsin ISNA group, and stable angina pectoris was found in 10 out of 13
      casesin non-ISNA group(P<0.01). (2) Quantitative analysis of OCT showed that the
      lumen area was less in ISNA group than in non-ISNA group((3.45+/-1.82)mm(2) vs.
      (4.17+/-1.68)mm(2), P<0.01), and neointimal area(3.89(2.26, 5.52)mm(2) vs.
      2.96(1.99, 4.22)mm(2), P<0.01), neointimal load (53.15(40.18, 67.30)% vs.
      41.54(32.08, 56.91)%, P<0.01), neointimal thickness(0.98(0.63, 1.36)MUm vs.
      0.72(0.51, 1.03)MUm, P<0.01) were higher in ISNA group than in non-ISNA
      group.(3)Qualitative analysis of OCT showed that the prevalence of homogeneous
      intima was less in the ISNA group than in the non-ISNA group ((41.42+/-22.56)%
      vs.(72.06+/-18.68)%, P<0.05), on the contrary, the heterogeneous intima was more
      common in the ISNA group ((58.57+/-22.56)% vs. (27.94+/-18.68)%, P<0.05). There
      was no significant difference between two groups in the peri-stentmicrovessels
      (9/12 vs. 5/13,P>0.05), and prevalence of intraintimalmicrovessels was higher in
      the ISNA group than in non-ISNA group (7/12 vs. 2/13, P<0.05). In addition, thin
      cap fibrous plaque(7/12 vs. 0, P<0.01), disrupted intima with visible cavity
      (7/12 vs. 1/13, P<0.05),andintraluminal red thrombus(7/12 vs. 1/13, P<0.05) were
      significantly higher in ISNA group than in non-ISNA group. Conclusions: Results
      of OCT show that ISNA occurs frequently in patients with ISR after DES
      implantation. The stent implantation time, incidence of chronic kidney disease
      and higher low-density lipoprotein cholesterol level are associated with the
      formation of ISNA in these patients.

PMID- 29374938
TI  - [Research on the relationship between atmospheric inhalable particulate matter
      and cardiovascular diseases burden in Tianjin].
AB  - Objective: To evaluate the association between atmospheric inhalable particulate
      matter (PM(10)) concentration and cardiovascular diseases burden in Tianjin.
      Methods: The data on daily mean concentrations of main pollutants (PM(10),
      nitrogen dioxide(NO(2)) and sulfur dioxide(SO(2))), meteorological factors
      (temperature and relative humidity) and population death monitoring data in
      Tianjin, from January 1, 2001 to December 31, 2010, were collected and analyzed
      in this study. The death counts and years of life lost were simultaneously used
      as the indicators of disease burden. The generalized additive model was used to
      assess the associations between PM(10) and daily death counts and years of life
      lost due to cardiovascular system diseases in Tianjin by adjusting the
      confounding factors such as long-term trend, seasons, meteorological factors and
      other factors related to the long-term variability. Results: The daily average
      concentration of PM(10) was 117.6 MUg/m3 in Tianjin during 2001 to 2011. The
      daily average number of deaths of cardiovascular system diseases, cerebrovascular
      diseases and ischemic heart diseases in Tianjin were 38.4, 14.8 and 17.2 people
      respectively, and the daily average years of life lost were 776.8, 306.5 and
      326.1 person years respectively. The effects of PM(10) on the daily death counts
      of the three diseases categories were statistically significant (all P<0.01) in
      Tianjin and the maximum effect occurs at the moment when PM(1)0 was at moving
      average concentration of today and lagged 1-day (Lag01). The effects of
      decreasing order were ischemic heart diseases, cardiovascular system diseases and
      cerebrovascular diseases, excess risks were 0.53% (95% CI 0.35%-0.71%), 0.40%
      (95%CI 0.28%-0.53%) and 0.38% (95%CI 0.19%-0.56%). The effects of atmospheric
      PM(10) on the years of life lost of the three diseases were also statistically
      significant on the different lag days (all P<0.01) in Tianjin and the maximum
      effect of PM(10) appeared in Lag01. The effects from the largest to the lowest
      were 2.86 (95%CI 1.79-3.93) person years for cardiovascular system diseases, 1.59
      (95%CI 0.95-2.23) person years for ischemic heart diseases and 1.07 (95%CI 0.43
      1.71) person years for cerebrovascular diseases, respectively. In multi-pollutant
      models, after controlling SO(2), the effect of PM(10) on the daily life loss of
      above 3 kinds of diseases was higher than that of single pollutant model. In
      contrast, after controlling SO(2) or SO(2) with NO(2), the effect was lower.
      After controlling NO(2), the effect of PM(10) on the daily life loss of
      cerebrovascular disease was no longer statistically significant (P>0.05).
      Conclusions: Exposure to atmospheric PM(10) can significantly increase the
      cardiovascular diseases burden in Tianjin, especially for ischemic heart
      diseases. These results suggested that particular attention should be paid to
      reduce the exposure to atmospheric inhalable particulate matter for patients with
      ischemic heart diseases.

PMID- 29374940
TI  - [Percutaneous closure of anastomotic leakage after Standford A aortic dissection
      surgery using Ampatzer Vascular Plug III].

PMID- 29374939
TI  - [Comparison of arterial stiffness in non-hypertensive and hypertensive population
      of various age groups].
AB  - Objective: To investigate the impact of blood pressure and age on arterial
      stiffness in general population. Methods: Participants who took part in 2010,
      2012 and 2014 Kailuan health examination were included. Data of brachial ankle
      pulse wave velocity (baPWV) examination were analyzed. According to the WHO
      criteria of age, participants were divided into 3 age groups: 18-44 years group
      (n=11 608), 45-59 years group (n=12 757), above 60 years group (n=5 002).
      Participants were further divided into hypertension group and non-hypertension
      group according to the diagnostic criteria for hypertension (2010 Chinese
      guidelines for the managemengt of hypertension). Multiple linear regression
      analysis was used to analyze the association between systolic blood pressure
      (SBP) with baPWV in the total participants and then stratified by age groups.
      Multivariate logistic regression model was used to analyze the influence of blood
      pressure on arterial stiffness (baPWV>=1 400 cm/s) of various groups. Results:
      (1)The baseline characteristics of all participants: 35 350 participants
      completed 2010, 2012 and 2014 Kailuan examinations and took part in baPWV
      examination. 2 237 participants without blood pressure measurement values were
      excluded, 1 569 participants with history of peripheral artery disease were
      excluded, we also excluded 1 016 participants with history of cardiac-cerebral
      vascular disease. Data from 29 367 participants were analyzed. The age was
      (48.0+/-12.4) years old, 21 305 were males (72.5%). (2) Distribution of baPWV in
      various age groups: baPWV increased with aging. In non-hypertension population,
      baPWV in 18-44 years group, 45-59 years group, above 60 years group were as
      follows: 1 299.3, 1 428.7 and 1 704.6 cm/s, respectively. For hypertension
      participants, the respective values of baPWV were: 1 498.4, 1 640.7 and 1 921.4
      cm/s. BaPWV was significantly higher in hypertension group than non-hypertension
      group of respective age groups (P<0.05). (3) Multiple linear regression analysis
      defined risk factors of baPWV: Multivariate linear regression analysis showed
      that baPWV was positively correlated with SBP(t=39.30, P<0.001), and same results
      were found in the sub-age groups (t-value was 37.72, 27.30, 9.15, all P<0.001,
      respectively) after adjustment for other confounding factors, including age, sex,
      pulse pressure(PP), body mass index (BMI), fasting blood glucose (FBG), total
      cholesterol (TC), smoking, drinking, physical exercise, antihypertensive
      medications, lipid-lowering medication. (4) Multivariate logistic regression
      analysis of baPWV-related factors: After adjustment for other confounding
      factors, including age, sex, PP, BMI, FBG, TC, smoking, drinking, physical
      exercise, antihypertensive medication, lipid-lowering medication, multivariate
      logistic regression analysis showed that risks for increased arterial stiffness
      in hypertension group were higher than those in non-hypertension group, the OR in
      participants with hypertension was 2.54 (2.35-2.74) in the total participants,
      and same results were also found in sub-age groups, the ORs were 3.22(2.86-3.63),
      2.48(2.23-2.76), and 1.91(1.42-2.56), respectively, in each sub-age group.
      Conclusion: SBP is positively related to arterial stiffness in different age
      groups, and hypertension is a risk factor for increased arterial stiffness in
      different age groups. Clinical Trial Registry Chinese Clinical Trial Registry,
      ChiCTR-TNC-11001489.

PMID- 29374941
TI  - [Refractory heart failure in a patient with antiphospholipid syndrome].

PMID- 29374942
TI  - [The existing forms of circulating microRNA and its diagnostic value in acute
      myocardial infarction].

PMID- 29374943
TI  - [Analysis on the stationed system for detached medical officer in the Song
      Dynasty].
AB  - The stationed system for detached medical officer, designated by the Royal Hanlin
      Department, was an important management system in the Song Dynasty for medical
      aid and epidemic prevention. The selection of the officers was based on the test
      results of the candidates. The dispatch of such medical officers was considered
      comprehensively on the local conditions, with priority given to those provinces
      and counties in shortage of such officers, and sent them in order based on the
      duration of their working time.The primary responsibility of the stationed
      medical officers was to provide medical services to locally stationed troops, at
      the same time also involved in treating and saving people as epidemics occurred
      in local places. The term of their service was two years. The system is a kind of
      relatively mature medical management practices, which could improve the level of
      local army medical services and control the occurrence and spread of epidemics
      effectively.

PMID- 29374944
TI  - [The affinity between Le family of Tong Ren Tang and acu-moxibustion as viewed
      from Mian xue tang zhen jiu ji cheng (Mian Xuetang's Synthetic Work of Acu
      moxibustion)].
AB  - This compilation process of Mian xue tang zhen jiu ji cheng(Mian Xuetang's
      Synthetic Work of Acu-moxibustion)was quite mysterious, the book's advent
      coincidentally met with several major historical events which made its value of
      decoding its historical functions far beyond its academic value. The editor of
      this book is Le Xianyang, the founder of Tong Ren Tang. While compiling this
      book, he also made a replica of Ming-Dynasty's Zhengtong bronze statue. More than
      200 years later, Le Jingyu, the 12th generation of the Le family revised Ming
      Tang Tuinherited from his ancestors and engraved Ming Tang Tuon the stone for its
      standardization. This great achievement of Le family was no less than the
      recasting of the Tiansheng bronze statue and the reengraving Tong ren shu xue
      zhen jiu tu jing(Illustrated Manual of Acupuncture Points of the Bronze Figure)
      by support of state power for building the Beijing Imperial Hospital in the
      eighth year of the Zhengtong reign (1443).

PMID- 29374945
TI  - [Literature research on Changshan (Radix Dichroae)].
AB  - Originally named Hengshan, it is recorded firstly in the Shen nong ben cao
      jing(Shennong's Classic of Materia Medica). Its name is changed as Changshan in
      the Song Dynasty and still used today. Changshan is a cosmopolitan species, and
      the producing area expands from Sichuan, Hubei, Shaanxi and Henan during the Wei
      and Jin Dynasties to nowadays more than 10 provinces, such as the south of the
      Yangtze River, Gansu etc. Before the Tang Dynasty, Changshan's original plant is
      Orixa japonicaThunb., which is changed to Dichroa febrifugaLour. from the Song
      Dynasty as its main orthodox product.

PMID- 29374946
TI  - [Textual research on Fengqing Jixueteng (Kadsura interior A. C. Smith), Kunming
      Jixueteng (Millettia dielsiana Harms ex Diels) and Jixueteng (Spatholobus
      suberectus Dunn)].
AB  - Being a common materia medica, the confusion of Jixuetengcaused by the homonyms
      of different substances for Jixuetengis always very complicated. Fengqing
      JixuetengPaste was first created in the Qing Dynasty. Fengqing Jixuetengwas
      derived from the dried stems of a variety of species in KadsuraJuss. and
      SchisandraMichx. from Schisandracea; while Kunming Jixueteng, derived from the
      dried stem of Millettia dielsianaHarms ex Diels, was firstly recorded in the Zhi
      wu ming shi tu kao(Textual Research on Reality and Titles of Plants). The
      earliest records of Spatholobus suberectusDunn as the original plant of
      Jixuetengwas in Guang xi ben cao xuan bian(Selected Compilation of Chinese
      Materia Medica in Guangxi). It was not until 1997 that Spatholobus suberectusDunn
      was recorded as an origin of orthodox product of Jixuetengin the Chinese
      Pharmacopoeia. At present, the origins of Jixuetengis very complicated as
      recorded in different provincial standards, including three species of three
      genus from Leguminosae.The varieties of species from KadsuraJuss. and
      SchisandraMichx. had long been used as Fengqing Jixueteng, but currently the most
      extensively used one is Spatholobus suberectusDunn as Jixueteng. There are more
      differences in records of Jixuetengin history up to the present, hence, further
      investigation and research on Jixuetengis still necessary.

PMID- 29374947
TI  - [Brief introduction to the development of ancient history of paediatric diagnosis
      of traditional Chinese medicine].
AB  - As an important part of paediatric science, paediatric diagnosis was in the
      initial stage of its development before the Song Dynasty. The main measures of
      diagnosing diseases were observation and pulse palpation, especially the latter.
      The rapid development of paediatrics in the Song Dynasty necessitated
      thepaediatric diagnosis to develop further, emphasizing the spiritual expressions
      of the eyes and fingerprint, with its special features gradually developed in the
      period of the Jin and Yuan Dynasties.During this period, the paediatrics
      diagnosis was developed on the basis of the previous generations, with equal
      importance paid to both observation and pulse feeling. In the period of the Ming
      and Qing Dynasties the four paediatric diagnostics were constantly enriched with
      attentions paid to the use of multiple approaches and thus the diagnostics was
      perfected day by day.

PMID- 29374948
TI  - [Distribution of Xin'an TCM physicians and their medical works and the reasons of
      its formation of medical center].
AB  - Based on the living times, native places and medical works of Xin'an TCM
      physicians described in the Xin an ming yi kao(Textual Research of Famous
      Physicians of Xin'an Region), the geographical distribution of ancient TCM
      physicians was analyzed by using Excel software. It is found that Xin'an medicine
      was originated from the Eastern Jin Dynasty and highly developed in the Qing
      Dynasty, and the number of its TCM physicians in the Ming and Qing Dynasties was
      large than the summation of those from the Eastern Jin Dynasty to the Ming
      Dynasty. In regard to the district, the distribution of Xin'an TCM physicians was
      characterized by more in the southeastern and less in the northwestern parts,
      forming a distribution area concentrated in the three counties of Shexian, Wuyuan
      and Xiuning. The reasons of such concentration of Xin'an TCM physicians are
      closely related to the economic growth, the influence of Neo-Confucianism and the
      density of population.

PMID- 29374949
TI  - [The national anti-opium-smoking campaigns across the country in the Republican
      Period].
AB  - Anti-opium-smoking had been the key policy of successive central and local
      governments from the late Qing Dynasty to the Republican Period. Since the
      establishment of the Nanjing Provisional Government in January 1912, the Anti
      opium-smoking campaign had culminated across the country. Under the support of
      the government, the "National Anti-Opium Association of China" and "Association
      of Chinese People Rejecting Opium" were established which made an important
      contribution to China's anti-opium-smoking campaign.Yunnan, Shaanxi,
      Heilongjiang, Zhejiang, Shanghai and other local governments also combined with
      local specific circumstances to make anti-opium-smaking policy for punishing
      severely the opium cultivation, trade and opium smoking, thus, the overrun of
      opium began to be brought under an overall control.

PMID- 29374950
TI  - [Measures, motivation and influence of Yan Xishan's support for traditional
      Chinese medicine in the Republic of China].
AB  - In Shanxi Province, governed by Yan Xishan during the Republic of China,
      traditional Chinese medicine (TCM) is in a climate of relative tolerance on the
      whole, under its supporting policy. A TCM Improving Society was organized by Yan
      Xishan himself as president. Whereafter, a series of activities are carried out
      by the Society, such as the establishments of an Affiliated Hospital, a Learning
      School of TCM, and creation of Medical Magazineetc., all of which was supported
      by Yan through providing financial resources and manpower. The reasons for Yan's
      such supports, in addition to his deeply influenced by traditional Chinese
      culture and his recognition on the therapeutic effects of TCM, might lie in the
      account of the practical reality of economy and people's livelihood in Shanxi
      Province. All his such measures not only provided a guarantee for local TCM
      development, but also exerted an important impact on local provincial medical
      structure of the day.

PMID- 29374951
TI  - [Comparison on the function of rose as interpreted by traditional Chinese
      medicine and medicine of Uighur ethnic group].
AB  - As a kind of edible herbal plant, rose is recorded both in the literature of Han
      medicine and medicine of Uighur ethnic group, yet with different understanding on
      its function and different clinical application as well. Both Han and Uighur
      medicine maintain that rose possesses the functions of improving one's look and
      moisturizing the skin, aromatic deodorant and invigorating spleen to treat
      inflammation and damage, hematemesis, pain and diarrhea etc. In addition, rose is
      also used to treat wind bi(impediment or migratory arthralgia), acute mastitis,
      breast lump and depression in Han medicine, while in Uighur medicine, it is also
      used to treat constipation, palpitation, flat wart and dry throat.

PMID- 29374952
TI  - [Textual research on a prescription, "Pill of Semen Plantaginis" in the Tangut
      medical documents unearthed in Khara-Khoto].
AB  - A prescription, "Pill of Semen Plantaginisfor Treating All Diseases"
      (I(HB).N(O).4384) carried in the Tangut medical documents unearthed in Khara
      Khoto was published in the 10(th)Volume of Heishuicheng Manuscript Collected in
      Russia. The prescription is composed of Herba Cistanches, Radix Achyranthis,
      Semen Plantaginis, white poria, Cortex Cinnamomi, Radix Aconiti preparata, Semen
      Cuscutaeand baked ginger, whose main function is invigorating kidney yang and
      nourishing kidney essence. This prescription has a close relationship with the
      Han prescription in central plain of China which may be based on certain lost
      Chinese medical book.

PMID- 29374953
TI  - [Research on Japanese monograph of comprehensive dietetic materia medica, the Pao
      chu bei yong wo ming ben cao (Japanese Materia Medica Prepared for Kitchen)].
AB  - Japanese physicians of Edo Period (1603-1867) wrote many dietetic books, by
      combining the knowledge system (content and compiling style) and thoughts of diet
      therapy from China with local condition in Japan. Among them, the Pao chu bei
      yong wo ming ben cao(Japanese Materia Medica Prepared for Kitchen), written by
      Mukai Genshou, a physician in the early Edo, is the earliest comprehensive work
      of dietetic materia medica. In this book, the choice and usage of Japanese
      dietetic materia medica reveals obvious Japanese local color, including the name,
      morphology, cultivation, collection, identification, nature and flavor, and
      indication etc., reflecting the sprouting idea of edible herbal plant at the
      beginning of Edo period and the characteristic of absorbing Chinese diet thoughts
      by Japanese physician. This is the important first-hand historical material to
      understand the development of Japanese dietetic herbalism in early Edo and its
      dietotherapy culture.

PMID- 29374954
TI  - Stimulatory Action of Telmisartan, an Antagonist of Angiotensin II Receptor, on
      Voltage-Gated Na+ Current: Experimental and Theoretical Studies.
AB  - Telmisartan (Tel) is recognized as a non-peptide blocker of AT1R. Whether this
      agent has anydirect effects on ion currents remains unexplored. In whole-cell
      current recordings, addition of Telincreased the peak amplitude of voltage-gated
      Na+ (NaV) current (INa) accompanied by the increasedtime constant of INa
      inactivation in differentiated NSC-34 motor neuron-like cells. Tel-stimulated
      INain these cells is unlinked to either blockade of AT1R or activation of
      peroxisome proliferator-activatedreceptor gamma (PPAR-gamma). In order to explore
      how this compound affects the amplitude and kineticsof INa in neurons, a Hodgkin
      Huxley-based (HH-based) model designed to mimic effect of Tel on thefunctional
      activities of neurons was computationally created in this study. In this
      framework, theparameter for h inactivation gating variable, which was changed in
      a stepwise fashion, was implementedto predict changes in membrane potentials (V)
      as a function of maximal Na+ (GNa), K+ conductance(GK), or both. As inactivation
      time course of INa was increased, the bifurcation point of V versusGNa became
      lower, and the range between subcritical and supercritical values at the
      bifurcation of Vversus GK correspondingly became larger. During a slowing in INa
      inactivation, the critical boundarybetween GNa and GK was shifted towards the
      left. Simulation studies demonstrated that progressiveslowing in the inactivation
      time course of INa resulted in unanticipated increase of neuronalexcitability by
      mimicking the effect of Tel in neuronal cells. Collectively, Tel can directly
      interact withthe NaV channel to increase peak INa as well as to slow INa
      inactivation. It is thus highly likely that theeffects of Tel or its structurally
      similar drugs could be another intriguing mechanism underlying
      theirpharmacological actions in neurons or neuroendocrine cells occurring in
      vivo.

PMID- 29374955
TI  - Genistein Suppressing the ROS-Induced Hypersensitivity of Rat Vagal Lung C-Fiber
      Afferents through an ERalpha-Mediated Mechanism.
AB  - Reactive oxygen species (ROS) may induce hypersensitivity of vagal lung C-fibers
      (VLCFs) throughthe interaction of transient receptor potential ankyirn 1 (TRPA1)
      and P2X receptors. Genistein isa soy-derived isoflavone that exerts antioxidant
      effects by binding to estrogen receptors (ERs), ERalphaand ERbeta. We
      investigated whether ER activation by genistein can suppress H2O2-mediated
      VLCFhypersensitivity and identified the types of ERs involved. Results revealed
      that subcutaneous injectionof genistein or 4,4',4"-(4-propyl-[1H]-pyrazole-1,3,5
      triyl)trisphenol (PPT, a selective ERalpha agonist) canattenuate H2O2-induced
      VLCF hypersensitivity. The suppressive effects of genistein and PPT wereinhibited
      by an additional treatment with ICI182780 (a nonselective ER antagonist) or 1,3
      bis(4-hydroxyphenyl)-4-methyl-5-[4-(2-piperidinylethoxy)phenol]-1H-pyrazole
      dihydrochloride (MPP,a selective ERalpha antagonist). Treatment with a
      combination of PPT, HC030031 (a TRPA1 receptorantagonist), and iso
      pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS, a P2X
      receptorantagonist) did not further inhibit H2O2-induced VLCF hypersensitivity as
      compared with combinedHC030031 and iso-PPADS treatment. In conclusion, ERalpha
      activation by genistein can suppress H2O2-induced VLCF hypersensitivity through
      its functional interaction with TRPA1 and P2X receptors.

PMID- 29374956
TI  - Antitumorigenic Effects of ZAKbeta, an Alternative Splicing Isoform of ZAK.
AB  - Sterile alpha motif (SAM)- and leucine-zipper-containing kinase (ZAK) plays a
      role in theregulation of cell cycle progression and oncogenic transformation. The
      ZAK gene generates twotranscript variants, ZAKalpha and ZAKbeta, through
      alternative splicing. In this study, we identified thatZAKalpha proteins were
      upregulated in tumor tissues, whereas ZAKbeta proteins were mostly expressedin
      corresponding normal tissues. The ectopically expressed ZAKbeta proteins in
      cancer cells inhibitedcancer cell proliferation as well as anchorage-independent
      growth. The ZAKbeta:ZAKalpha protein ratioplayed a role in the regulation of the
      cyclic adenosine monophosphate (cAMP) signaling pathway,whereas high ZAKbeta
      protein levels led to the activation of cAMP response element binding protein
      1(CREB1) and exerted antitumor properties. Overexpression of ZAKbeta or CREB1
      cDNAs in cancercells inhibited anchorage-independent growth and also reduced the
      levels of cyclooxygenase 2 (Cox2)and beta-catenin proteins. Cancer cells treated
      with doxorubicin (Doxo) resulted in the switching fromthe expression of ZAKalpha
      to ZAKbeta and also inhibited cancer cell growth in soft agar, demonstratingthat
      pharmacological drugs could be used to manipulate endogenous reprogramming
      splicing eventsand resulting in the activation of endogenous antitumorigenic
      properties. We showed that the twoZAK transcript variants, ZAKalpha and ZAKbeta,
      had opposite biological functions in the regulation oftumor cell proliferation in
      that ZAKbeta had powerful antitumor properties and that ZAKalpha couldpromote
      tumor growth.

PMID- 29374957
TI  - Protective Effect of L-Theanine on Haloperidol-Induced Orofacial.
AB  - Tardive dyskinesia (TD) is a severe side effect of chronic neuroleptic treatment
      consisting ofabnormal involuntary movements, characterized by orofacial
      dyskinesia (OD). Haloperidol (HAL)-induced OD has been widely used as an animal
      model to study the neuropathophysiology of humanTD with its pathophysiology
      strongly associated with striatal oxidative stress. L-Theanine (LT), oneof the
      major amino acid components in green tea, has potent antioxidative effects and is
      able to protectagainst various oxidative injuries. In this study, we examined the
      potential protective effects of LTon HAL-induced behavioral and neurochemical
      dysfunction in rats. HAL treatment (1 mg/kg i.p.for 21 days) induced significant
      increases (P < 0.001) in the frequency of vacuous chewing movement(VCM) and
      tongue protrusion (TP) as well as the duration of facial twitching (FT). LT
      treatment (100,300 mg/kg orally for 35 days, starting 14 days before HAL
      injection) was able to prevent most of theHAL-induced OD. LT treatment was also
      able to reduce the lipid peroxidation (LPO) production, andenhance the
      antioxidation power in striatum from rats with HAL treatment. The above results
      indicatethat LT has a protective role against HAL-induced OD, probably via its
      powerful antioxidative properties.Thus, LT may have a clinically relevant
      therapeutic effect in delaying or treating TD.

PMID- 29374958
TI  - Modulatory Effect of Concomitant Administration of Insulin and Vanadium on
      Inflammatory Biomarkers in Type 2 Diabetic Rats: Role of Adiponectin.
AB  - The aim of this study is to investigate the effect of vanadium and/or insulin on
      the proinflammatorybiomarkers in type 2 diabetes mellitus (T2DM) rat model. Sixty
      male Sprague Dawleyrats were divided into six groups (n = 10). Control group,
      control vanadium group, T2DM group,insulin-treated diabetic group, vanadium
      treated diabetic group, and concomitant insulin andvanadium-treated diabetic
      group. At the end of the experiment, serum glucose, insulin, lipid profile,tumor
      necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), high sensitivity C
      reactive protein (hs-CRP), intercellular adhesion molecule-1 (ICAM-1), vascular
      cell adhesion molecule-1 (VCAM-1) andadiponectin were measured. Administration of
      insulin and/or vanadium significantly decreased in theplasma levels of glucose,
      lipid profile, TNF-alpha, IL-6, hs-CRP, ICAM-1, and VCAM-1 with
      significantincrease in adiponectin in comparison to the diabetic group.
      Concomitant administration of insulinand vanadium significantly improved the
      above measured parameters compared to either insulin orvanadium treatment. Based
      on our results we can conclude that administration of both vanadiumand insulin
      reduced the low-grade systemic inflammation in T2DM, through reduction of both
      proinflammatorycytokines and adhesion molecules and increase adiponectin.

PMID- 29374959
TI  - Impact of High Altitude on Maternal Serum Leptin Level and its Correlation With
      Oxidative Stress and Endothelial Inflammatory Markers in Preeclamptic Women.
AB  - Involvement of leptin in the pathogensis of preeclampsia (PE) is still a
      controversy subject.Several researches reported the changes in serum leptin in
      high altitude (HA) residents. The aimof the present work was to investigate the
      impact of oxidative stress (OS) induced by HA residenceon maternal serum leptin
      in PE and if there was a significant correlation between the serum leptinwith
      either OS or endothelial inflammatory markers. One hundred fifty eight pregnant
      women wereincluded in this study, divided into: low altitude normal pregnancies
      (NL), HA normal pregnancies(NH), low altitude preeclamptic (PL), and HA
      preeclamptic (PH) who presented to the obstetrics andgynecology outpatient clinic
      in both Muhayl (500 m over sea level) and Abha General Hospitals (allof them
      resident at Alsoda district with the average altitude 2700 m over sea level).
      Serum leptin,superoxide dismutase (SOD) activity, malondialdehyde (MDA), plasma
      nitrite/nitrate (NOx), serumtumor necrosis factor alpha (TNF-alpha), interleukin
      6 (IL-6), blood urea nitrogen (BUN) and creatininewere determined. Both NH and PL
      groups showed significant increases in leptin (P < 0.01), SOD (P <0.01), MDA (P <
      0.001), NOx (P < 0.001), TNF-alpha (P < 0.001) and IL-6 (P < 0.001) compared with
      theNL group without any significant changes between both groups. The PH group
      showed significantaccentuation of the previously measured parameters (P < 0.001
      for all) compared with all othergroups (NL, NH and PL groups). We can conclude
      that the combination of PE and HA residenceresulted in significantly elevated
      maternal serum leptin suggesting involvement of leptin in thepathogenesis of PE
      accentuated by HA residence.

PMID- 29374960
TI  - Cytological Features That Differentiate Follicular Neoplasm from Mimicking
      Lesions.
AB  - BACKGROUND: It is difficult to correctly diagnose follicular neoplasms (FNs) on
      fine-needle aspiration cytology (FNAC) because it shares many cytological
      features with other mimicking lesions. The aim of this study was to identify the
      cytological features that differentiate FNs from mimicking lesions. METHODS: We
      included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC,
      and included their subsequent histological diagnoses. We evaluated the
      cytological architectural pattern and nuclear features of the lesions according
      to their histological groups. RESULTS: The final histological diagnoses of the
      116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas
      (40%) including follicular variant, and seventeen cellular nodular hyperplasias
      (15%). Regardless of the final histological diagnosis, microfollicular pattern
      was observed in most cases. On the other hand, trabecular pattern was identified
      in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and
      ground glass chromatin were found in only some papillary thyroid carcinomas.
      CONCLUSIONS: This study shows that the trabecular pattern is a representative
      cytological feature of FNs that can be used to distinguish FNs from mimicking
      lesions. In addition, nuclear shape and chromatin pattern can be used to further
      confirm the diagnosis of FNs from mimicking lesions through FNAC.

PMID- 29374962
TI  - Introduction to the Special Issue: Interventions to Reduce Challenging Behavior
      Among Individuals With Autism Spectrum Disorder.
AB  - The prevalence of autism spectrum disorder (ASD) is on the rise. In addition to
      the social communication skill deficits and restrictive repetitive behaviors and
      interests, many individuals with ASD engage in challenging behavior. Challenging
      behavior is associated with a multitude of negative outcomes. Challenging
      behavior may cause harm to the individual with ASD as well as limit opportunities
      for educational, vocational, and social participation and development. In
      addition, caregivers experience high stress and low quality of mental health. As
      a result, challenging behavior warrants intervention that is specifically
      tailored to the unique characteristics of individuals with ASD. The purpose of
      this Special Issue is to showcase recent research in the treatment of challenging
      behavior for individuals with ASD. This two-part Special Issue contains 12
      studies that range from systematic and quality reviews of the intervention
      literature, to innovative treatment approaches, to studies that develop and
      evaluate treatments for restrictive and repetitive behaviors and interests.

PMID- 29374961
TI  - Effect of Lifestyle Modification Using a Smartphone Application on Obesity With
      Obstructive Sleep Apnea: A Short-term, Randomized Controlled Study.
AB  - OBJECTIVES: To investigate the short-term effects of a lifestyle modification
      intervention based on a mobile application (app) linked to a hospital electronic
      medical record (EMR) system on weight reduction and obstructive sleep apnea
      (OSA). METHODS: We prospectively enrolled adults (aged >20 years) with witnessed
      snoring or sleep apnea from a sleep clinic. The patients were randomized into the
      app user (n=24) and control (n=23) groups. The mobile app was designed to collect
      daily lifestyle data by wearing a wrist activity tracker and reporting dietary
      intake. A summary of the lifestyle data was displayed on the hospital EMR and was
      reviewed. In the control group, the lifestyle modification was performed as per
      usual practice. All participants underwent peripheral arterial tonometry
      (WatchPAT) and body mass index (BMI) measurements at baseline and after 4 weeks
      of follow-up. RESULTS: Age and BMI did not differ significantly between the two
      groups. While we observed a significant decrease in the BMI of both groups, the
      decrease was greater in the app user group (P <0.001). Apnea-hypopnea index,
      respiratory distress index, and oxygenation distress index did not change
      significantly in both groups. However, the proportion of sleep spent snoring at
      >45 dB was significantly improved in the app user group alone (P =0.014). In
      either group, among the participants with successful weight reduction, the apnea
      hypopnea index was significantly reduced after 4 weeks (P =0.015). Multiple
      regression analyses showed that a reduction in the apnea-hypopnea index was
      significantly associated with BMI. CONCLUSION: Although a short-term lifestyle
      modification approach using a mobile app was more effective in achieving weight
      reduction, improvement in OSA was not so significant. Long-term efficacy of this
      mobile app should be evaluated in the future studies.

PMID- 29374963
TI  - A Randomized Controlled Pilot Trial of the Unified Protocol for Transdiagnostic
      Treatment of Emotional Disorders in Children.
AB  - The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in
      Children (UP-C) is an intervention for children aged 7 to 13 targeting high
      negative emotion, emotional reactivity, and emotion regulation deficits common
      across emotional disorders. Our objective was to collect pilot randomized
      controlled trial (RCT) data on the efficacy of the UP-C, comparing UP-C with an
      active, anxiety-focused intervention. Participants were 47 children with at least
      one primary anxiety disorder; approximately one half had elevated depression
      symptoms. Participants received either UP-C or the anxiety-focused control
      treatment. No condition-related differences were found with respect to diagnostic
      remission and anxiety symptoms. However, differences in favor of UP-C were
      observed with respect to treatment response at follow-up, depression symptoms,
      sadness dysregulation, and cognitive reappraisal. Results provide preliminary
      evidence that the UP-C may be at least as efficacious in treating anxiety as well
      supported anxiety-specific treatment protocols and may produce greater gains in
      certain emotion reactivity and regulation variables.

PMID- 29374964
TI  - Identifying What Is Known About Improving Operating Room to Intensive Care
      Handovers: A Scoping Review.
AB  - The purpose is to provide a descriptive overview of relevant material exploring
      improvement of handovers from the operating room (OR) to intensive care unit
      (ICU). An online search (MEDLINE, Cochrane, EMBASE, CINAHL, and Joanna Briggs),
      including gray literature and relevant reference lists, was completed. In all,
      4574 unique citations were screened and 155 full-text reviews performed; 65
      articles were included in the final analysis. The majority of articles discuss an
      ideal structure for handover (n = 63; 97%); 43 (66%) articles mentioned
      strategies for implementing such an approach. Only 21 (32%) explicitly described
      formal quality improvement (QI) methods. Few explored project sustainability and
      impact of a structured handover on patient safety outcomes (n = 15, 23%).
      Published literature suggests that there is a significant gap in evidence of
      measured patient outcomes from standardization of OR to ICU handover processes.
      Identifying formal QI strategies used to sustain standardized handover processes
      will allow accurate measurement of patient outcomes.

PMID- 29374965
TI  - The Impact of a Transition of Care Program on Acute Myocardial Infarction
      Readmission Rates.
AB  - Hospital discharge is a high-risk time period, and acute myocardial infarction
      (AMI) patients often have early readmissions. The authors hypothesized that a
      multifaceted AMI care coordination program would reduce early hospital
      readmission rates. The outcomes of patients receiving care coordination (n = 304)
      were compared to patients receiving standard care (n = 192). Multivariable
      analyses of the outcomes were conducted by conditional logistic regression of
      propensity score matched sets. The primary outcome-hospital readmission within 30
      days of discharge-occurred in 18% of standard care patients and 11.8% of care
      coordination patients. Patients receiving care coordination demonstrated a 48%
      reduction in odds of readmission within 30 days (odds ratio = 0.52; P = .04; 95%
      CI = 0.28-0.97). These results are the first to demonstrate that inclusion in an
      AMI-specific care coordination program is associated with a significantly lower
      risk of 30-day hospital readmission.

PMID- 29374966
TI  - Evaluation of Hematocrit Influence on Self-Monitoring of Blood Glucose Based on
      ISO 15197:2013: Comparison of a Novel System With Five Systems With Different
      Hematocrit Ranges.
AB  - INTRODUCTION: ISO 15197:2013 recommends testing procedures and acceptance
      criteria for the evaluation of influence quantities such as hematocrit on
      measurement results with systems for self-monitoring of blood glucose (SMBG). In
      this study, hematocrit influence was evaluated for a novel SMBG system (system A)
      and five other systems with different hematocrit ranges based on ISO 15197:2013.
      METHODS: Test procedures were performed with one test strip lot for each system.
      Each system was tested within the hematocrit range indicated in the
      manufacturer's labeling (system A: 10-65%, B: 15-65%, C: 20-60%, D: 35-60%, E: 30
      60%, F: 30-55%). According to ISO 15197:2013, clause 6.4.2, venous blood samples
      were used for the evaluation of hematocrit influence. The evaluation was
      performed for three glucose concentration categories (30-50 mg/dL, 96-144 mg/dL,
      and 280-420 mg/dL). For each glucose concentration category, at least five
      different hematocrit levels were investigated. RESULTS: The novel system A and
      systems B, E, and F complied with the tested lot with the defined criteria and
      showed <=10 mg/dL and <=10% difference between the test sample and the respective
      control sample with a hematocrit value of 42% +/- 2% for BG concentrations <100
      mg/dL and >=100 mg/dL, respectively. Two systems showed >10% difference at
      glucose concentrations >=100 mg/dL. CONCLUSIONS: Remarkable hematocrit influence
      within the labeled hematocrit range was obtained in two systems with the tested
      reagent system lot. Adequate SMBG systems should be carefully chosen by patients
      and their health care professionals, particularly for patients with increased and
      decreased hematocrit values.

PMID- 29374967
TI  - Association Between Second Metatarsal Length and Forefoot Loading Under the
      Second Metatarsophalangeal Joint.
AB  - BACKGROUND: Metatarsal length is believed to play a role in plantar plate
      dysfunction, although the mechanism through which progressive injury occurs is
      still uncertain. We aimed to clarify whether length of the second metatarsal was
      associated with increased plantar pressure measurements in the forefoot while
      walking. METHODS: Weightbearing radiographs and corresponding pedobarographic
      data from 100 patients in our practice walking without a limp were
      retrospectively reviewed. Radiographs were assessed for several anatomic
      relationships, including metatarsal length, by a single rater. Pearson
      correlation analyses and multiple linear regression models were used to determine
      whether metatarsal length was associated with forefoot loading parameters.
      RESULTS: The relative length of the second to first metatarsal was positively
      associated with the ratio of peak pressure beneath the respective
      metatarsophalangeal joints ( r = 0.243, P = .015). The relative length of the
      second to third metatarsal was positively associated with the ratios of peak
      pressure ( r = 0.292, P = .003), pressure-time integral ( r = 0.249, P = .013),
      and force-time integral ( r = 0.221, P = .028) beneath the respective
      metatarsophalangeal joints. Although the variability in loading predicted by the
      various regression analyses was not large (4%-14%), the relative length of the
      second metatarsal (to the first and to the third) was maintained in each of the
      multiple regression models and remained the strongest predictor (highest
      standardized beta-coefficient) in each of the models. CONCLUSIONS: Patients with
      longer second metatarsals exhibited relatively higher loads beneath the second
      metatarsophalangeal joint during barefoot walking. These findings provide a
      mechanism through which elongated second metatarsals may contribute to plantar
      plate injuries. LEVEL OF EVIDENCE: Level III, comparative study.

PMID- 29374969
TI  - Prospective Comparison of Point-of-Care Device and Standard Analyzer for
      Monitoring of International Normalized Ratio in Outpatient Oral Anticoagulant
      Clinic.
AB  - Point-of-care testing (POCT) coagulometers are increasingly being used in the
      hospital setting and patients' self-testing. We determined the agreement of
      prothrombin time international normalized ratio (INR) results by POCT
      coagulometer and laboratory instrument through a comparative analysis and
      investigated whether the results of POCT coagulometer can reliably be used
      without being confirmed by standard laboratory analyzer. A total of 200 INR
      measurements by POCT coagulometer (CoaguChek XS Pro) and laboratory analyzer
      (Sysmex CS2000i) were compared using Passing-Bablok regression analysis and Bland
      Altman plot. Agreement of the INR measurement was further analyzed in relation to
      dosing decision. The correlation of INR measurements between CoaguChek XS Pro and
      Sysmex CS2000i was excellent (correlation coefficient = 0.973). The overall mean
      difference was 0.21 INR +/- 0.32 (range: 1.7-0.44). The mean difference was found
      to get increased as INR results increased and was 0.09 in the subtherapeutic
      range (<=1.9 INR), 0.29 INR in the therapeutic range (2.0-3.0 INR), while 0.4 INR
      in the supratherapeutic range (>3.0 INR). The overall agreement was excellent
      (kappa = 0.916) and overall 11 (5.5%) of 200 INR measurements showed a difference
      in dosing decision between the 2 instruments. The positive bias of POC-INR is
      evident in the supratherapeutic range which could affect the dosing decision
      requiring confirmation with the laboratory INR measurement.

PMID- 29374968
TI  - Fibrinolytic Deficit and Platelet Activation in Atrial Fibrillation and Their
      Postablation Modulation.
AB  - This study aims to examine the effects of atrial fibrillation (AF) on the
      expression of the cellular mediators plasminogen activator inhibitor 1 (PAI-1)
      and CD40 ligand (CD40-L). Additionally, the effect of catheter ablation on the
      levels of the aforementioned biomarkers was also examined. In this prospective
      study, plasma samples were collected from patients with AF at baseline prior to
      ablation and at 1 and 3 months postablation. There was a statistically
      significant increase in CD40-L at baseline in patients with AF compared to
      control ( P = .0034). There was a statistically significant decrease in CD40-L
      levels postablation at both 1 month ( P < .0001) and 3 months ( P < .0001)
      compared to baseline. Baseline levels of PAI-1 were elevated compared to the
      control group (mean 19.55 +/- 2.17 ng/mL vs 4.85 +/- 0.41 ng/mL) and a
      statistically significant decrease in circulating PAI-1 levels 1 month
      postablation ( P = .05) was noted compared to preablation levels. These data
      suggest that inflammation plays an important role in the pathogenesis of AF and
      that these cellular mediators are modulated by catheter ablation.

PMID- 29374970
TI  - Transient hallucinations during interpersonal stress in an adolescent with
      borderline personality disorder.

PMID- 29374971
TI  - Biotinylated-lipid bilayer coated mesoporous silica nanoparticles for improving
      the bioavailability and anti-leukaemia activity of Tanshinone IIA.
AB  - The oral bioavailability and anti-leukaemia activity of Tanshinone IIA (TanIIA)
      were enhanced by using biotinylated-lipid bilayer coated mesoporous silica
      nanoparticles (Bio-LB-MSNs) as a vehicle. The in vitro release of TanIIA from
      TanIIA@MSNs was significantly higher than that of the TanIIA powder (p < .05).
      The in vitro cellular uptake of TanIIA by Caco-2 was increased by loading drug
      into the Bio-LB-MSNs more than those of the compared nanovehicles without biotin
      modification. The apparent in situ permeability coefficient (Papp) of TanIIA@Bio
      LB-MSNs showed nearly 2.5-, 1.6- and 1.3-fold improvement compared with the
      TanIIA powder, TanIIA@MSNs and TanIIA@LB-MSNs. Following oral administration of
      TanIIA@Bio-LB-MSNs in rats, the area under the plasma concentration-time curves
      (AUC) of TanIIA was 3.4-, 1.9- and 2.4-fold larger than those in the groups
      received a pure TanIIA powder, TanIIA@MSNs or TanIIA@LB-MSNs, indicating that
      drug bioavailability was enhanced by using MSNs as a vehicle, and further
      improved significantly through biotin modification. The in vitro anti-leukaemia
      activity of TanIIA was also enhanced after being loaded into nanoparticles and
      modification, with 50% inhibitive concentration (IC50) of NB4 cells at 6.5 MUM
      for TanIIA@Bio-LB-MSN. In conclusion, Bio-LB-MSNs are a promising vehicle to
      improve the oral bioavailability and anti-leukaemia activity of the poorly water
      soluble drug TanIIA.

PMID- 29374972
TI  - Association between depressive symptoms, CD4 count and HIV viral suppression
      among HIV-HCV co-infected people.
AB  - Depressive symptoms are associated with poor HIV viral control and immune
      recovery among people living with HIV. However, no prior studies assessed this
      association exclusively among people co-infected with HIV-hepatitis C virus
      (HCV). While people with HIV only and those with HIV-HCV co-infection share many
      characteristics, co-infected people may become more susceptible to the effects of
      depressive symptoms on health outcomes. We assessed this association exclusively
      among people co-infected with HIV-HCV in Canada using data from the Food Security
      & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC).
      Stabilized inverse probability weighted marginal structural model was used to
      account for potential time-varying confounders. A total of 725 participants were
      enrolled between 2012 and 2015. At baseline, 52% of participants reported
      depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count
      was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times
      (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had
      comparable CD4 count to people who did not experience depressive symptoms (fold
      change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a
      risk factor for incomplete short-term HIV viral suppression among people co
      infected with HIV-HCV. Therefore, depressive symptoms screening and related
      counseling may improve HIV related health outcomes and reduce HIV transmission.

PMID- 29374973
TI  - Sub-millimetre accurate human hand kinematics: from surface to skeleton.
AB  - A highly accurate human hand kinematics model and identification are proposed.
      The model includes the five digits and the palm arc based on mapping function
      between surface landmarks and estimated joint centres of rotation. Model
      identification was experimentally performed using a motion tracking system. The
      evaluation of the marker position estimation error, which is on sub-millimetre
      level across all digits, underlines model quality and accuracy. Noticeably, with
      the development of this model, we were able to improve various modelling
      assumptions from literature and found a basic linear relationship between surface
      and skeleton rotational angles.

PMID- 29374974
TI  - Impact of stochastically generated heterogeneity in hazard rates on individually
      randomized vaccine efficacy trials.
AB  - Background/aims Network structure and individuals' level of exposure to a
      pathogen can impact results from efficacy evaluation studies of interventions
      against infectious diseases. Heterogeneity in infection risk can cause randomized
      groups to increasingly differ as a trial progresses and as more high-risk
      individuals become infected (described in prior work as the "frailty"
      phenomenon). Here, we show the impact this phenomenon can have on an individually
      randomized trial of a leaky vaccine in which all participants are exchangeable a
      priori. Methods We model a vaccine trial by generating a network of individuals
      grouped into communities, which are connected to a larger main population. We
      then simulate an epidemic, deterministically and with time-varying transmission
      rates in the main population and stochastically in the communities. The disease
      natural history follows a susceptible-exposed-infectious-recovered model.
      Simulation results are used to estimate vaccine efficacy [Formula: see text] with
      a Cox proportional hazards model. Results We find downward bias in [Formula: see
      text] associated with low connectivity between communities in the study
      population and high force of infection, even when all participants in the trial
      are exchangeable at the time of randomization. This phenomenon arises because the
      stochastic dynamics in such a setting randomly lead to community-level variation
      in the force of infection. Stratifying a Cox model by community alleviates this
      bias with no loss of power. Conclusion Understanding and accounting for the
      impact of heterogeneous hazard rates can allow for more accurate estimates of
      [Formula: see text] in epidemic settings.

PMID- 29374976
TI  - Multimodal retinal imaging in a case of an unsuccessful suicide attempt with
      sildenafil.

PMID- 29374975
TI  - Synthesis and biological evaluation of stilbene derivatives coupled to NO donors
      as potential antidiabetic agents.
AB  - The work is focused on the design of drugs that prevent and treat diabetes and
      its complications. A novel class of stilbene derivatives were prepared by
      coupling NO donors of alkyl nitrate and were fully characterised by NMR and other
      techniques. These compounds were tested in vitro activity, including alpha
      glucosidase inhibitory activity, aldose reductase (AR) inhibitory activity and
      advanced glycation end products (AGEs) formation inhibitory activity. A class of
      modified compounds could play a significant effect for treatment of diabetic
      complications. Target compounds 3e and 7c offered a potential drug design concept
      for the development of therapeutic or preventive agents for diabetes and its
      complications.

PMID- 29374977
TI  - Navigating the health-care system in community: Perspectives from Asian immigrant
      parents of children with special health-care needs.
AB  - Children with special health-care needs (CSHCNs) face notable barriers to health
      care access and to receiving quality and family-centered care, despite higher
      health-care utilization rates. Within the population of CSHCNs, there are
      significant inequities in health-care quality impacting immigrants who have
      migrated to the United States. However, little is known about the experiences and
      needs of Asian immigrant families who have CSHCNs. This study aimed to explore
      how Asian immigrant parents of CSHCNs view their child's health-care access,
      quality, and utilization. We conducted semi-structured qualitative interviews
      with 22 Vietnamese- and Cantonese-speaking parents of CSHCNs. Participants were
      recruited through community partners. Interviews were transcribed, translated,
      and coded using content analysis. Participants were generally satisfied with
      their children's care and had strong relationships with their primary care
      doctors who were often culturally 'matched'. However, participants experienced
      several important and culturally specific barriers, including gaps in their
      understanding of the health-care system, language barriers, and a sense of
      alienation. Parents frequently turned to informal and community supports for
      assistance in navigating the US health-care system. Further research to
      understand the drivers of health disparities and policy level solutions is
      warranted.

PMID- 29374978
TI  - Misconceptions about traumatic brain injury among educators: has anything changed
      over the last 20 years?
AB  - PURPOSE: To examine educational professionals' knowledge and understanding of
      childhood brain injury. MATERIALS AND METHODS: Educational professionals from all
      schools in the state of Victoria, Australia, were invited to participate in an
      online cross-sectional survey consisting of 20 questions assessing knowledge of
      concussion and 30 questions examining knowledge of traumatic brain injury (n =
      364). RESULTS: On average, participants correctly answered 16/20 (80%) questions
      about concussion and 24.3/30 (81%) about traumatic brain injuries. Participants
      who had previously taught a child with a brain injury demonstrated greater
      knowledge of traumatic brain injury, but not concussion, than those who had not.
      There were no differences in knowledge of concussion or brain injury between
      participants who had and had not attended a briefing session about concussion.
      Misconceptions displayed by educators predominantly related to the ongoing
      effects and impact of both concussion and traumatic brain injury, including
      effects on emotion, cognition, and social behaviour, as well as the increased
      risk of multiple injuries following an initial brain injury. When participants'
      responses to the brain injury questionnaire were compared with results reported
      by Farmer and Johnson-Gerard in 1997 using the same questionnaire, many of the
      same misconceptions were evident in the two samples of educational professionals.
      CONCLUSIONS: Although educators demonstrated reasonable understanding of
      concussion and brain injury, some gaps in knowledge were apparent. Providing
      educational professionals with further training and professional development
      regarding childhood brain injuries would enhance their preparedness to manage
      students with these injuries in the school environment. Implications for
      Rehabilitation Mild to moderate brain injuries are relatively common among school
      aged children, and educators may be required to manage and support students with
      these injuries in the school environment. This study shows that educators
      generally have a good understanding of the symptoms and immediate effects of
      brain injuries, but have gaps in knowledge regarding the potential
      socioemotional, behavioural, and cognitive difficulties and vulnerabilities to
      multiple injuries that may be present during recovery. Pre-service training and
      professional development may increase educators' understanding and capacity to
      accommodate the needs of students with brain injuries.

PMID- 29374979
TI  - 99mTc-labelled multifunctional polyethylenimine-entrapped gold nanoparticles for
      dual mode SPECT and CT imaging.
AB  - In this study, we report the synthesis, characterization and utilization of 99mTc
      labelled polyethylenimine-entrapped gold nanoparticles (99mTc-Au-PENPs) for dual
      mode single-photon emission computed tomography/computed tomography (SPECT/CT)
      imaging applications. Polyethylenimine (PEI) was selected as a platform to
      conjugate with diethylene triamine pentacetate acid (DTPA) and polyethylene
      glycol monomethyl ether to synthesize Au PENPs, followed by acetylation or
      hydroxylation modification of the remaining PEI surface amine groups and
      radiolabelling of 99mTc. The generated multifunctional 99mTc-Au-PENPs with
      different surface groups (acetyl or hydroxyl) were characterized via different
      methods. The Au PENPs before 99mTc labelling are colloidally stable,
      haemocompatibility and noncytotoxic at an Au concentration up to 100 MUM. The
      99mTc-labelled Au PENPs exhibit high radiochemical purity, good stability and
      SPECT/CT imaging performance of different organs and lymph node. The designed
      strategy to use the radionuclide labelling technique and PEI-facilitated
      versatile nanoplatform may be extended to develop various novel nanoprobes for
      precision imaging applications.

PMID- 29374980
TI  - Imaging devices - today's innovations and tomorrow's potential.

PMID- 29374981
TI  - Mechanisms of the enhanced antibacterial effect of Ag-TiO2 coatings.
AB  - It has been demonstrated that Ag-TiO2 nanocomposite coatings with excellent
      antimicrobial activity and biocompatibility have the potential to reduce
      infection problems. However, the mechanism of the synergistic effect of Ag-TiO2
      coatings on antibacterial efficiency is still not well understood. In this study,
      five types of Ag-TiO2 nanocomposited coatings with different TiO2 contents were
      prepared on a titanium substratum. Leaching tests indicated that the
      incorporation of TiO2 nanoparticles into an Ag matrix significantly promoted Ag
      ion release. Surface energy measurements showed that the addition of TiO2
      nanoparticles also significantly increased the electron donor surface energy of
      the coatings. Bacterial adhesion assays with Escherichia coli and Staphylococcus
      aureus demonstrated that the number of adhered bacteria decreased with increasing
      electron donor surface energy. The increased Ag ion release rate and the
      increased electron donor surface energy contributed to an enhanced antibacterial
      efficiency of the coatings.

PMID- 29374982
TI  - Protecting UK adolescents and adults against meningococcal serogroup B disease.
AB  - INTRODUCTION: Meningococcal serogroup B disease (MenB) is endemic in the UK and
      continues to cause the majority of invasive meningococcal disease. Two broadly
      protective protein-based MenB vaccines are now licensed and available, both with
      wide age indications. Whilst the UK recently became the first country to
      routinely vaccinate infants against MenB, a recommendation has not yet been
      extended to older age groups who can also now benefit from these vaccines. Areas
      covered: This review summarizes the evidence supporting the rationale for
      adolescents and adults in the UK to consider MenB vaccination. Expert commentary:
      Although MenB disease is rare, the UK reports one of the highest annual incidence
      rates within the European region, with over a third of cases occurring in those
      aged 10+ years. Overall, the case fatality rate following MenB disease in the UK
      is 4.2% but can be more than twice as high in teenagers and adults than in
      infants, and survivors are often left with life-changing disabling sequelae. MenB
      outbreaks are unpredictable and continue to occur in regions where it is endemic.
      These outbreaks often affect students attending school or university, with living
      on a campus being an important risk factor. Concerned individuals in this age
      group should consider MenB vaccination.

PMID- 29374983
TI  - Management of twin-twin transfusion syndrome with an extremely short cervix.
AB  - The objective of this study was to describe the management and perinatal outcomes
      of patients with twin-twin transfusion syndrome (TTTS) and an extremely short
      cervical length (CL). This retrospective study examined 17 patients with TTTS and
      a preoperative CL <=1.0 cm who had undergone laser surgery and perioperative
      cervical cerclage placement successfully. In this subset of patients, the median
      interval between surgery and delivery was 9.6 (range 2.1-13.9) weeks and only one
      patient had PPROM within 3 weeks of surgery. The median gestational age at
      delivery was 30.9 (range 23.1-37.6) weeks, 30-day survival of at-least-one twin
      was 88.2% and dual survivorship was 82.4%. Overall, patients with TTTS and a
      preoperative CL <=1.0 cm who were able to undergo successful laser surgery and
      emergent cerclage placement had favourable outcomes. Impact statement The
      management of patients with twin-twin transfusion syndrome (TTTS) and extremely
      short cervical length (CL) varies between foetal surgery centres. This study
      demonstrates that laser surgery and cerclage placement in such patients are not
      only technically feasible, but also can result in favourable perinatal outcomes.
      Patients with an extremely short CL should not be uniformly excluded from laser
      surgery for TTTS.

PMID- 29374984
TI  - Clinical applicability of Tokyo guidelines 2018/2013 in diagnosis and severity
      evaluation of acute cholangitis and determination of a new severity model.
AB  - OBJECTIVE: To determine the diagnostic accuracy of Tokyo guidelines (TG)
      2018/2013 (TG18/TG13) and predictors of poor prognosis in acute cholangitis.
      METHODS: Retrospective 1-year study of consecutive hospital admissions for acute
      cholangitis. Prognosis was defined in terms of 30 d in-hospital mortality.
      RESULTS: Of the 183 patients with acute cholangitis, diagnostic accuracy based on
      Charcot's triad, TG07 and TG18/TG13 was 67.8, 86.9 and 92.3% (p < .001),
      respectively. Regarding severity based on TG18/TG13, 30.6% of cases were severe.
      A poor prognosis was found in 10.9% of patients. After multivariate analysis,
      systolic blood pressure <90 mmHg (OR 11.010; p < .001), serum albumin <3 g/dL (OR
      1.355; p = .006), active oncology disease (OR 3.818; p = .006) and malignant
      aetiology of obstructive jaundice (OR 2.224; p = .021) were independent
      predictors of poor prognosis. The discriminative ability of the model with these
      four variables was high (AUROC 0.842; p < .001), being superior to TG18/TG13
      (AUROC 0.693; p = .005). CONCLUSIONS: TG18/TG13 showed high diagnostic accuracy
      in acute cholangitis. Compared with TG18/TG13, the simplified severity model >=2
      allows easy selection of patients who will benefit from admission to the
      intensive care unit and early biliary decompression.

PMID- 29374985
TI  - Preptin in women with polycystic ovary syndrome.
AB  - INTRODUCTION: Polycystic ovary syndrome (PCOS) patients, frequently develop
      metabolic complications, such as insulin resistance (IR), impaired carbohydrate
      metabolism, dyslipidemia, obesity. Among the new markers responsible for
      metabolic disorders, preptin seems to be of great significance. MATERIAL: One
      hundred and thirty-four women aged 17-45 were enrolled. PCOS was diagnosed in 73
      women on the basis of ESHRE-ASRM criteria. Non-PCOS group consisted of 61 women
      with regular menstruation matched for nutritional status. METHODS: All women
      underwent anamnesis, physical examination, anthropometric measurements, the
      abdominal ultrasound examination, and dual energy X-ray absorptiometry (DXA).
      Serum adropin levels were determined by ELISA. Biochemical and hormonal
      (testosterone, androstenedione, LH, FSH, estradiol) measurements were also
      performed. Insulin resistance indices (HOMA, QUICKI, Matsuda) and free androgen
      index (FAI) were calculated with the test results according to the standard
      formula. For all comparisons, statistical significance was defined by p <= .05.
      RESULTS: Serum preptin levels were significantly higher in the PCOS group. No
      significant correlations between preptin level and metabolic and hormonal markers
      were observed. The logistic regression analysis demonstrated that serum preptin
      level was an independent factor differentiating the two groups. CONCLUSIONS:
      Serum preptin levels were significantly higher in women with PCOS compared with
      controls. This peptide might be an independent predictor of PCOS in the future.

PMID- 29374986
TI  - Sense of Self in Alzheimer's Research Participants.
AB  - The sense of self is vulnerable in people with Alzheimer's disease (AD), and
      might be positively and negatively influenced by research participation. The
      purpose of this study was to describe how people with AD express their experience
      of being a research participant with respect to their sense of self. Interviews
      and support group conversations involving 13 people with mild and moderate AD
      were analyzed using qualitative content analysis. Three themes were constructed:
      contributing to an important cause, gaining from participating, and experiencing
      risks and drawbacks. Participants described contributing to research as being in
      line with their lifelong values and lifestyles. They expressed contentment and
      pride about being research participants, emphasized their positive relationships
      with the researchers, and described participation as a meaningful activity. When
      research procedures threatened their sense of self, they were able to reason
      about risks and decline participation.

PMID- 29374987
TI  - It Takes an Army of Reviewers.

PMID- 29374988
TI  - The Effects of Timing of Ankle Blocks in Forefoot, Midfoot, or Hindfoot
      Reconstruction With the Use of an Ankle Tourniquet.
AB  - BACKGROUND: Ankle blocks are used in the ambulatory surgery setting to control
      postoperative pain, which is often worst in the first 24 hours after surgery. We
      conducted a trial to determine whether the timing of ankle block administration
      in relation to ankle tourniquet inflation has an effect on perceived pain and
      narcotic consumption. METHODS: A prospective randomized study was conducted
      between August 2015 and January 2016. Patients were assigned to three groups. In
      group A, an ankle block was performed before ankle tourniquet inflation; in group
      B, immediately after ankle tourniquet inflation; and in group C, immediately
      after ankle tourniquet inflation with additional local anesthetic placed around
      the incision at the end of the procedure. Pain was assessed by a visual analogue
      scale (VAS) score, which was recorded at discharge, 24 hours, 48 hours, and 2
      weeks after surgery. Narcotic consumption was recorded at 24 and 48 hours after
      surgery. RESULTS: The only statistically significant difference in mean VAS
      scores occurred at 24 hours, when patients who received an ankle block after
      tourniquet inflation with local incisional anesthetic at closure (group C) had a
      mean VAS score 2.8 points lower (3.5 vs 6.3; P = .025) than those who received
      only an ankle block after tourniquet inflation (group B). There was no difference
      in narcotic consumption between groups at 24 and 48 hours. CONCLUSIONS: The
      timing of ankle block in relation to tourniquet inflation did not have an effect
      on pain control in forefoot, midfoot, and hindfoot reconstruction. The
      synergistic effect of an ankle block with additional incisional anesthetic at
      closure, is more effective than ankle block alone and is the ideal combination
      for postoperative pain control in foot surgery. LEVELS OF EVIDENCE: Therapeutic,
      Level II: Prospective, comparative trial.

PMID- 29374989
TI  - KLF16 suppresses human glioma cell proliferation and tumourigenicity by targeting
      TFAM.
AB  - BACKGROUND: This study aims to via unveiling the novel mechanisms of KLF16 in
      regulating expression of genes involved in glioma. METHODS: KLF16 or KLF16-siRNA
      was transfected to U87MG cells by lentivirus. Colony formation assay was applied
      for detecting cell proliferation. MTT assay was adopted to assess cell viability.
      TUNEL assay was selected to evaluate cell apoptosis. Flow cytometry was used to
      determine cell cycle. Real-time PCR was performed to test mRNA expression.
      Western blot was used to detect protein level. Luciferase assay was applied to
      confirm the regulatory relationship between KLF16 and Mitochondrial transcription
      factor A (TFAM). Chromatin immunoprecipitation was adopted to test the protein
      binding site. The nude mouse transplantation tumour experiment was selected to
      test cancer cell proliferation in vivo. RESULTS: KLF16 was decreased in glioma
      cells and tissues. KLF16 obviously restrained U87MG cell proliferation both in
      vivo and in vitro. KLF16 transfection reduced mRNA and protein levels related to
      cell proliferation. KLF16 targeted a putative binding site near the transcription
      start sites (TSSs) of TFAM gene, thus suppressing glioma cell proliferation.
      KLF16-siRNA exhibited the opposite impact. KLF16 presented significant negative
      correlation with TFAM level in glioma patients. CONCLUSIONS: KLF16 is a key
      regulator of glioma cell proliferation by directly targeting TFAM.

PMID- 29374990
TI  - Comparative inhalation toxicity of ethyltoluene isomers in rats and mice.
AB  - The C9 alkylbenzenes, composed mostly of ethyltoluenes and trimethylbenzenes,
      comprise 75-90% of the naphtha fraction of crude oil. Occupational and
      environmental exposure to C9 alkylbenzenes occur via inhalation. We conducted
      short-term inhalation studies on the ethyltoluene isomers (2-, 3- or 4-) to
      select one isomer for more comprehensive studies. Male Hsd:Sprague Dawley rats
      and female B6C3F1/N mice (n = 10) were exposed by nose-only inhalation to 2-, 3-
      or 4-ethyltoluene (0, 1000 or 2000 ppm) or cumene (a reference compound: 0, 500
      or 1000 ppm) 3 h/day, 5 days/week, for 2 weeks. Clinical observations included
      abnormal gait and delayed righting reflex. Rats and mice exposed to 2000 ppm 2
      ethyltoluene and mice exposed to 2000 ppm 4-ethyltoluene were euthanized early in
      moribund condition; no exposure-related deaths were observed with 3-ethyltoluene
      or cumene. Histopathology of selected tissues revealed that the nose and liver
      (rats and mice) and lung (mice only) to be toxicity targets. In the mouse lung,
      all compounds except 4-ethyltoluene produced bronchial and bronchiolar
      hyperplasia. In rats and mice, 2-ethyltoluene was the only compound to produce
      lesions in the nose and liver: in mice, squamous metaplasia and neutrophilic
      inflammation of the respiratory epithelium and atrophy and degeneration of the
      olfactory epithelium were observed in the nose and centrilobular hypertrophy and
      necrosis were observed in the liver. In rats, 2-ethyltoluene exposure produced
      atrophy of the olfactory epithelium in the nose and centrilobular necrosis in the
      liver. Based on mortality, body weight effects and histopathology, the 2
      ethyltoluene isomer was the most potent isomer.

PMID- 29374991
TI  - Association between maternal depression and maternal sensitivity from birth to 12
      months: a meta-analysis.
AB  - Maternal sensitivity plays a central role in shaping children's development
      across a number of domains, and may be disrupted by depression. The current meta
      analysis quantified the magnitude of the association between depression and
      maternal sensitivity, defined broadly as timely, contingent, and appropriate
      responding to infants' cues, from birth to 12 months. Across k = 48 studies and n
      = 4,934 mother-infant dyads, the aggregate effect size between depression and
      maternal sensitivity was r = -.16, p < .0001, indicating that mothers with higher
      depression levels were less sensitive than mothers with lower depression levels.
      Studies that compared a depressed group with a nondepressed/control group had
      larger effect sizes (r = -.35, p < .0001) than studies that examined depression
      within a single sample of either unselected cases or clinical-only cases (r = 
      .11, p < .001), suggesting that clinical levels of depression may pose a
      particular threat to sensitive parenting. Clinical implications (e.g. screening,
      prevention) are discussed.

PMID- 29374992
TI  - Lower urinary tract symptoms/benign prostatic hyperplasia and erectile
      dysfunction: from physiology to clinical aspects.
AB  - Erectile dysfunction, prostatic hyperplasia and lower urinary tract symptoms hare
      important pathogenetic links. Endothelial dysfunction and hormonal alterations
      represent the main aspects. The present article examines the anatomical,
      physiological, and pathophysiological characteristics of this association,
      finalizing the text to an interpretation of the clinical management of these
      patients based on these functional considerations.

PMID- 29374993
TI  - The effect of metabolic syndrome on Bell's palsy recovery rate.
AB  - OBJECTIVE: This study investigated the effects metabolic syndrome (MetS) and its
      factors such as diabetes mellitus (DM), hypertension (HTN), obesity,
      hypertriglyceridemia (high TG) and low high-density lipoprotein cholesterol (low
      HDL-C) on the recovery rate of patients with BP. METHODS: The medical records of
      124 patients with BP were retrospectively reviewed. Patients were divided into a
      MetS group and a Non-MetS group according to the diagnostic criteria of MetS, and
      the demographic and clinical characteristics of the two groups at baseline and
      six months after BP onset were analyzed. RESULTS: Age was significantly higher in
      the MetS group than in the Non-MetS group (p < .05), but there were no
      significant differences in sex ratio, initial House-Brackmann (H-B) grade,
      initial electroneurography and initial electromyography (p > .05). The most
      common comorbidity of BP was high TG, followed by low HDL-C, HTN, obesity and DM.
      There were no differences in initial H-B grade in patients with and without each
      component of the MetS (p > .05). The recovery rate of BP was significantly lower
      in the MetS than in the Non-MetS group and was particularly affected by DM,
      obesity and high TG. CONCLUSIONS: Recovery rate op BP is lower in patients with
      than without MetS.

PMID- 29374994
TI  - UK O&G trainees' attitudes to caesarean delivery for maternal request.
AB  - We assessed the attitudes of UK Obstetrics and Gynaecology (O&G) trainees towards
      a caesarean delivery for maternal request (CDMR); and identified differences in
      attitude towards patients requesting CDMR and preferences for their own mode of
      delivery. An internet survey was constructed with questions covering trainees'
      personal preferences towards and experience of CDMR; attitudes to CDMR; and how
      they might treat patients making this request. From 02/2013 to 06/2013, the
      survey was sent electronically via email to all UK Deaneries to be forwarded to
      O&G trainees. Two hundred and forty O&G trainees participated; 78% female. 6/101
      (6%) respondents had opted for CDMR in their first pregnancy. 28/131 (21%) would
      choose CDMR in their first pregnancy. Reasons for CDMR included concerns about
      pelvic floor/perineum, safety of the baby and convenience. 105/226 (46.4%)
      disagreed or strongly disagreed, and 67 (29.6%) agreed or strongly agreed with
      CDMR. 75/128 (58.6%) of respondents would grant CDMR to a patient; reasons
      included maternal choice, psychological concerns of the mother, perineal injury,
      pelvic floor. Our results are encouraging: positive attitudes of trainees towards
      vaginal delivery may help to reduce the rising caesarean rate. Impact Statement
      What is already known on this subject: Over the last 30 years, the rate of
      caesarean section in the UK has trebled and currently accounts for 25% of all
      deliveries. The rate of caesarean section in the UK has risen to 25% of all
      deliveries, incurring a financial burden and an excess clinical risk. With
      pressure to keep the caesarean rates low, understanding the attitudes and
      experience of obstetricians in training is important. What the results of this
      study add: Six percent of obstetric trainees, or their partners who had children
      had chosen a caesarean delivery for maternal request (CDMR), consistent with the
      population average. Twenty one percent of those who had not had children would
      choose CDMR. Both groups cited concerns over the pelvic floor as the predominant
      reason. Fifty nine percent of respondents would grant patients' request for CDMR.
      29.6% of respondents agreed, and 46.4% disagreed with CDMR. Trainees' attitude to
      CDMR does not appear to be associated with whether or not they have had children,
      but does appear to be associated with whether they had experienced, or were
      planning to choose CDMR themselves in the future. What the implications are of
      these findings for clinical practice and/or further research: Training for
      obstetric trainees regarding the optimum way to manage patients' requests for,
      and clearer guidance on CDMR may be of benefit. It is important that
      obstetricians discuss the reasons behind such requests in order to individualise
      management.

PMID- 29374995
TI  - Effect of intraosseous injection versus inferior alveolar nerve block as primary
      pulpal anaesthesia of mandibular posterior teeth with symptomatic irreversible
      pulpitis: a prospective randomized clinical trial.
AB  - OBJECTIVE: This study sought to assess the success rate, effect on blood
      pressure, and pain of intraosseous injection (IO) and inferior alveolar nerve
      block (IANB) for pulpal anaesthesia of mandibular posterior teeth with
      symptomatic irreversible pulpitis as the primary anaesthetic technique. MATERIALS
      AND METHODS: This randomized clinical trial (IRCT2013022712634N1) was conducted
      on 60 patients between 18 and 65 years suffering from symptomatic irreversible
      pulpitis of a mandibular posterior tooth. Patients were randomly divided into two
      groups. Group one received IO while group two received IANB with 3% mepivacaine.
      After anaesthetic injection, success rate of pulpal anaesthesia was assessed by
      pulp testing in the two groups. Systolic and diastolic blood pressures of
      patients were compared before and after the anaesthetic injections. Level of pain
      during injection was scored using a visual analogue scale. The data were analyzed
      using SPSS version 20, t-test and chi square test at p = .05 level of
      significance. RESULTS: Success rate of IO (56.7%) was significantly higher than
      that of IANB (23.3%) (p = .008). There was no significant difference in pain
      during anaesthetic injection (p = .304) or change in systolic (p = .80) and
      diastolic (p = .28) blood pressures following injection between the two
      techniques. CONCLUSIONS: IO had a higher success rate than IANB for pulpal
      anaesthesia of mandibular posterior teeth with symptomatic irreversible pulpitis.
      Neither technique provided profound pulpal anaesthesia.

PMID- 29374996
TI  - Bone mineral density is compromised in very long-term survivors of irradiated
      childhood brain tumor.
AB  - INTRODUCTION: The increase in the number of childhood brain tumor survivors
      warrants detailed research to increase our knowledge regarding the possible
      physical and psychosocial adverse outcomes of tumor and tumor therapy. The aim of
      this study was to evaluate the current bone health by measuring the bone mineral
      density (BMD) in irradiated, adult long-term survivors of childhood brain tumors.
      MATERIAL AND METHODS: We studied a national cohort of 74 adult survivors of
      childhood brain tumors treated with irradiation in Finland between 1970 and 2008.
      Dual X-ray absorptiometry (DXA) was performed for the femoral necks, total hips,
      and lumbar spine. Laboratory tests were conducted for evaluating the pituitary,
      thyroid, and gonadal functions. The participants were interviewed, examined
      clinically, and the disease and treatment related data were retrieved from the
      patient files. RESULTS: One fourth of the patients (23.6%) had sex- and age
      normalized z-scores below the expected range for age (z-score <= -2.0). Mean BMD
      scores were decreased in all the DXA measurement sites. Male sex was associated
      with low BMD (p < .05), while body mass index (BMI) had a significant positive
      association with BMD (p < .01). Mode of irradiation (with or without spinal
      irradiation) or inclusion of chemotherapy in the treatment did not affect BMD
      significantly. However, patients with a ventriculoperitoneal shunt had lower BMD
      than those without a shunt (p < .05). Follicle stimulating hormone (FSH) and
      luteinizing hormone (LH) were negatively associated with BMD in women (p < .05).
      However, a higher cumulative dose of glucocorticoids during treatment was not
      associated with lower BMD, while low BMD was significantly associated with
      previous fractures in long bones. DISCUSSION: Low BMD should be taken in
      consideration in treatment of irradiated childhood brain tumor survivors
      especially in those with previous fractures in long bones.

PMID- 29374997
TI  - Popping the medical education bubble before it forms: It's about dollars and
      sense.
AB  - Headlines have previously acknowledged the risk of a "bubble and crash"
      phenomenon in the physician workforce pipeline. A growing number of medical
      career dissatisfiers, including emotional and physical burnout, loss of autonomy
      and burdensome regulations, compound the longstanding fundamental issue of the
      prohibitive direct and opportunity costs associated with medical training. For
      U.S. medical education and, in turn, healthcare to remain robust and high
      quality, creative solutions are needed to address the untenable physician debt-to
      income ratios and to ensure not only that the quantity and quality of medical
      school aspirants remains favorable to the profession, but that the profession
      remains responsible to its future members. Creating fiscally healthy physicians
      is a societal imperative.

PMID- 29374998
TI  - Burn Survivors' Near-Death Experiences: A Qualitative Examination.
AB  - Persons who come close to death but survive catastrophic accidents sometimes
      report very vivid experiences during times when their survival was in doubt, when
      they were believed to be dead, and during resuscitation efforts. This qualitative
      study builds upon existing research on near-death experiences (NDEs) by focusing
      on the oral accounts from a sample of individuals with large and life-threatening
      burns. The NDE accounts were obtained from burn survivors attending the Phoenix
      Society's World Burn Congress and are similar to reports by notable researchers (
      Greyson, 2003 ; Moody, 1975 ; Ring, 1980 ) while reflecting the uniqueness of the
      individual survivor's experiences. Six major themes are reported. Counselors and
      health professionals need to be aware of and educated about NDEs as these
      experiences can have profound effects upon the individual. Patients who have had
      NDEs may need to discuss them but fear professionals will reject their stories as
      being crazy.

PMID- 29375000
TI  - Intradiscal Expandable Balloon Distraction During Transforaminal Decompression
      for Lumbar Foraminal and Lateral Recess Stenosis.
AB  - Advanced videoendoscopic equipment (such as motorized drills, chisels, and
      rongeurs) facilitates the use of modern decompression tools through the inner
      working channel of the spinal endoscope using the transforaminal approach.
      Postoperative dysesthetic leg pain, however, is common because of irritation of
      the dorsal root ganglion. This article presents a novel surgical technique
      employing an expandable balloon placed into the hollow intervertebral space in
      patients without any functional disc tissue to distract the stenotic motion
      segment. This approach improves visualization, facilitates removal of bone during
      the decompression, and minimizes intraoperative manipulation of the exiting and
      traversing nerve roots. In a study of 52 targeted patients with symptomatic
      spinal stenosis at 60 levels (L2/3-1, L3/4-9, L4/5-28, and L5/S1-22) due to
      advanced degenerative changes of the intervertebral disc and facet joint complex
      contributing to both foraminal and lateral recess stenosis, only 2 of the 52
      patients complained of postoperative dysesthetic leg pain (3.85%) after
      undergoing this novel procedure. At the final 2-year follow-up, 80.9% of patients
      showed Excellent and Good outcomes according to modified Macnab criteria.

PMID- 29374999
TI  - Tumor-targeting Salmonella typhimurium A1-R combined with recombinant
      methioninase and cisplatinum eradicates an osteosarcoma cisplatinum-resistant
      lung metastasis in a patient-derived orthotopic xenograft (PDOX) mouse model:
      decoy, trap and kill chemotherapy moves toward the clinic.
AB  - In the present study, a patient-derived orthotopic xenograft (PDOX) model of
      recurrent cisplatinum (CDDP)-resistant metastatic osteosarcoma was treated with
      Salmonella typhimurium A1-R (S. typhimurium A1-R), which decoys chemoresistant
      quiescent cancer cells to cycle, and recombinant methioninase (rMETase), which
      selectively traps cancer cells in late S/G2, and chemotherapy. The PDOX models
      were randomized into the following groups 14 days after implantation: G1, control
      without treatment; G2, CDDP (6 mg/kg, intraperitoneal (i.p.) injection, weekly,
      for 2 weeks); G3, rMETase (100 unit/mouse, i.p., daily, for 2 weeks). G4, S.
      typhimurium A1-R (5 * 107 CFU/100 MUl, i.v., weekly, for 2 weeks); G5, S.
      typhimurium A1-R (5 * 107 CFU/100 MUl, i.v., weekly, for 2 weeks) combined with
      rMETase (100 unit/mouse, i.p., daily, for 2 weeks); G6, S. typhimurium A1-R (5 *
      107 CFU/100 MUl, i.v., weekly, for 2 weeks) combined with rMETase (100
      unit/mouse, i.p., daily, for 2 weeks) and CDDP (6 mg/kg, i.p. injection, weekly,
      for 2 weeks). On day 14 after initiation, all treatments except CDDP alone,
      significantly inhibited tumor growth compared to untreated control: (CDDP: p =
      0.586; rMETase: p = 0.002; S. typhimurium A1-R: p = 0.002; S. typhimurium A1-R
      combined with rMETase: p = 0.0004; rMETase combined with both S. typhimurium A1-R
      and CDDP: p = 0.0001). The decoy, trap and kill combination of S. typhimurium A1
      R, rMETase and CDDP was the most effective of all therapies and was able to
      eradicate the metastatic osteosarcoma PDOX.

PMID- 29375002
TI  - Bioactive compounds of the Mediterranean diet and prostate cancer.
AB  - OBJECTIVE: The purpose of this review is to examine the evidence on the effects
      of bioactive constituents of the Mediterranean diet (MeDi) on prostate cancer
      (PCa) risk. METHODS: The search for articles came from extensive research in the
      following databases: PubMed, Scopus, and Web of Science. We used the search terms
      "Mediterranean diet," "lycopene," "vitamin E," "vitamin C," "Selenium,"
      "resveratrol," "prostate cancer," and combinations, such as "lycopene and
      prostate cancer" or "resveratrol and prostate cancer." RESULTS: Numerous studies
      investigating the effect of various dietary nutrients on PCa have suggested that
      selenium is probably the most promising. Several studies reported reduced PCa
      risk associated with vitamin C and E intake, while other studies reported no
      association. Lycopene inhibits cell proliferation and inducts apoptosis, thus
      protecting against cancer. Also, it has been found in various in vivo and in
      vitro studies that resveratrol, inhibits PCa development. CONCLUSIONS: The high
      content of bioactive phytochemicals in the MeDi is of particular interest in the
      prevention of PCa. Further large-scale studies are required to clarify the effect
      of MeDi bioactive compounds on prostate health, in order to establish the role of
      this diet in the prevention of PCa.

PMID- 29375001
TI  - Simple geometry tribological study of osteochondral graft implantation in the
      knee.
AB  - Robust preclinical test methods involving tribological simulations are required
      to investigate and understand the tribological function of osteochondral repair
      interventions in natural knee tissues. The aim of this study was to investigate
      the effects of osteochondral allograft implantation on the local tribology
      (friction, surface damage, wear and deformation) of the tissues in the natural
      knee joint using a simple geometry, reciprocating pin-on-plate friction
      simulator. In addition, the study aimed to assess the ability of osteochondral
      grafts to restore a low surface damage, deformation and wear articulation when
      compared to the native state. A method was developed to characterise and quantify
      surface damage wear and deformation of the opposing cartilage-bone pin surface
      using a non-contacting optical profiler (Alicona Infinite Focus). Porcine 12 mm
      diameter cartilage-bone pins were reciprocated against bovine cartilage-bone
      plates that had 6 mm diameter osteochondral allografts, cartilage defects or
      stainless steel pins (positive controls) inserted centrally. Increased levels of
      surface damage with changes in geometry were not associated with significant
      increases in the coefficient of dynamic friction. Significant damage to the
      opposing cartilage surface was observed in the positive control groups. Cartilage
      damage, deformation and wear (as measured by change in geometry) in the xenograft
      (2.4 mm3) and cartilage defect (0.99 mm3) groups were low and not significantly
      different (p > 0.05) compared to the negative control in either group. The study
      demonstrated the potential of osteochondral grafts to restore the congruent
      articular surface and biphasic tribology of the natural joint. An optical method
      has been developed to characterise cartilage wear, damage and deformation that
      can be applied to the tribological assessment of osteochondral grafts in a whole
      natural knee joint simulation model.

PMID- 29375003
TI  - Local confinement and bedridden in the context of boundedness - The development
      of a conceptual definition based on an integrative review
AB  - Background: Local confinement and bedridden are important phenomena in nursing
      care. Nevertheless, conceptual definitions and appropriate nursing diagnoses are
      missing in the current nursing classification systems. Aim: The aim is to provide
      the basis for a conceptual definition. To this end, the current state of the
      German and English usage of the terms local confinement and bedridden are
      presented. At the same time, definitions of English-language terms, which are
      internationally widely recognized, are elaborated. Additionally, phenomena
      associated with local confinement and bedridden are recorded and delimited of
      each other. Method: The identification of the German and English conceptual usage
      takes place through an integrative literature review covering the period from
      1990 to 2016. Results: There are a variety of English-language terms of location
      confinement and bedridden. The concepts of homebound, wheelchairbound and
      bedridden form of local confinement and bedridden most extensively. Instability,
      immobility is connected as cause and inactivity as a consequence. In contrast to
      this is bedrest, which is ordered and temporally limited. Conclusions: Local
      confinement and bedridden are to be viewed through the definition of boundedness.
      The antecedents (instability, immobility) must be diagnosed to derive adequate
      interventions to avoid or alleviate the consequences.

PMID- 29375004
TI  - Predicted contributions of cytochrome P450s to drug metabolism in human liver
      microsomes using relative activity factor were dependent on probes.
AB  - Contributions of cytochrome P450 (CYP450) isoforms to drug metabolism are often
      predicted using relative activity factor (RAF) method, assuming RAF values were
      independent of probe. We aimed to report probe-dependent characteristic of RAF
      values using CYP3A4 or CYP2C9 probes. Metabolism of four CYP3A4 probes
      (testosterone, midazolam, verapamil and atorvastatin) and three CYP2C9 probes
      (tolbutamide, diclofenac and S-warfarin) in human liver microsomes (HLM) and cDNA
      expressed recombinant CYP450 (Rec-CYP450) systems were characterized and RAFCL
      value was estimated as ratio of probe intrinsic clearance in HLM to that in Rec
      CYP450. CYP450i contributions to metabolic reaction of a probe were predicted
      using other probes and compared with data from specific inhibitions.
      Contributions of CYP3A4 and CYP2C9 to metabolism of deoxypodophyllotoxin and
      nateglinide were also predicted. RAF values were dependent on probes, leading to
      probe-dependently predicted contributions. Predicted contributions of CYP3A4 to
      formations of 6beta-hydroxytestosterone, 1'-hydroxymidazolam, norverapamil, ortho
      hydroxyatorvastatin and para-hydroxyatorvastatin using other probes were 47.46
      219.46%, 21.62-98.87%, 186.49-462.44%, 21.87-101.15% and 53.62-247.97%,
      respectively. Predicted contributions of CYP3A4 and CYP2C9 to nateglinide
      metabolism were 8.18-37.84% and 36.08-94.04%, separately. In conclusion, CYP450i
      contribution to drug metabolism in HLM estimated using RAF approach were probe
      dependent. Therefore, contribution of each isoform must be confirmed by multiple
      probes.

PMID- 29375005
TI  - Everyday executive function in focal onset pediatric epilepsy on the parent
      report BRIEF2.
AB  - Executive function (EF) difficulties are a core neuropsychological feature of
      pediatric epilepsy, and parent-report measures of EF concerns are an important
      complement to task-based EF measures. The Behavior Rating Inventory of Executive
      Function (BRIEF) has shown sensitivity to parent-reported EF concerns in epilepsy
      and other pediatric populations. We compared profiles of parent-reported EF
      concerns using the BRIEF and its revision, the BRIEF2, in 117 pediatric patients
      with focal onset epilepsy to examine the clinical utility of the revised scale.
      We then compared BRIEF2 profiles between patients and age- and gender-matched
      healthy controls. Among patients, profiles on the BRIEF did not globally differ
      from the BRIEF2, and agreement was very good across scales. Patients and controls
      differed significantly on the BRIEF2, with patients showing higher EF
      difficulties reported by parents across most scales. High rates of clinical
      elevation among patients emerged on the Task Monitor, Plan/Organize, Working
      Memory, and Shift scales. Younger age of epilepsy onset, chronic epilepsy, and
      right hemisphere seizure focus were associated with higher parent-reported EF
      concerns. Findings suggest that the BRIEF2 demonstrates similar performance to
      the BRIEF among pediatric patients with focal onset epilepsy who are most at risk
      in the areas of task monitoring, working memory, planning and organization, and
      flexibility. These findings are informative when comparing literature across
      versions and provide additional insight into the nature of parent-reported EF
      difficulties among children with focal onset epilepsy.

PMID- 29375007
TI  - Recognition mechanism of Wilms' tumour suppressor protein and DNA triplets:
      insights from molecular dynamics simulation and free energy analysis.
AB  - The Wilms' tumour suppressor protein (WT1) plays a multifaceted role in human
      cancer processes. Mutations on its DNA recognition domain could lead to Denys
      Drash syndrome, and alternate splicing results in insertion of the tripeptide Lys
      Thr-Ser (KTS) between the third and fourth zinc fingers (ZFs), leading to changes
      in the DNA-binding function. However, detailed recognition mechanisms of the WT1
      DNA complex have not been explored. To clarify the mutational effects upon WT1
      towards DNA binding at the atomic level, molecular dynamics simulations and the
      molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) method were
      employed. The simulation results indicate that mutations in ZF domains (E427Q and
      Q369H) may weaken the binding affinity, and the statistical analyses of the
      hydrogen bonds and hydrophobic interactions show that eight residues (Lys351,
      Arg366, Arg375, Arg376, Lys399, Arg403, Arg424 and Arg430) have a significant
      influence on recognition and binding to DNA. Insertion of the tripeptide KTS
      could form an immobilized hydrogen-bonding network with Arg403, affecting the
      flexibility and angle of the linker between ZF3 and ZF4, thus influencing the
      recognition between the protein and the DNA triplet at its 5' terminus. These
      results represent the first step towards a thorough characterization of the WT1
      recognition mechanisms, providing a better understanding of the structure
      function relationship of WT1 and its mutants.

PMID- 29375006
TI  - Mechanisms that prevent catastrophic interactions between paternal chromosomes
      and the oocyte meiotic spindle.
AB  - Meiosis produces haploid gametes by accurately reducing chromosome ploidy through
      one round of DNA replication and two subsequent rounds of chromosome segregation
      and cell division. The cell divisions of female meiosis are highly asymmetric and
      give rise to a large egg and two very small polar bodies that do not contribute
      to development. These asymmetric divisions are driven by meiotic spindles that
      are small relative to the size of the egg and have one pole juxtaposed against
      the cell cortex to promote polar body extrusion. An additional unique feature of
      female meiosis is that fertilization occurs before extrusion of the second polar
      body in nearly all animal species. Thus sperm-derived chromosomes are present in
      the egg during female meiosis. Here, we explore the idea that the asymmetry of
      female meiosis spatially separates the sperm from the meiotic spindle to prevent
      detrimental interactions between the spindle and the paternal chromosomes.

PMID- 29375008
TI  - When patients hurt us.
AB  - In this thoughtful article, medical educators in various stages of their careers
      (resident, mid-career clinician-educators, medical school deans) reflect upon
      increasing reports of harassment and mistreatment of trainees by patients. In
      addition to providing a general overview of the limited literature on this topic,
      the authors describe their own experience collecting information on trainee
      mistreatment by patients at their institution. They explore the universal
      difficulty that educators face regarding how to best address this mistreatment
      and support both faculty and trainees. Given the current sociopolitical climate,
      there has never been a more urgent need to critically examine this issue. The
      authors call on the greater medical education community to join them in these
      important conversations.

PMID- 29375009
TI  - Spectroscopic evaluation of synthesized 5beta-dihydrocortisol and 5beta
      dihydrocortisol acetate binding mechanism with human serum albumin and their role
      in anticancer activity.
AB  - Our study focus on the biological importance of synthesized 5beta-dihydrocortisol
      (Dhc) and 5beta-dihydrocortisol acetate (DhcA) molecules, the cytotoxic study was
      performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell
      line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 MUM, respectively,
      whereas no toxicity in terms of cell viability was observed with HEK293 cell
      line. Further experiment proved that Dhc and DhcA induced 35.6 and 37.7% early
      apoptotic cells and 2.5, 2.9% late apoptotic cells, respectively, morphological
      observation of cell death through TUNEL assay revealed that Dhc and DhcA induced
      apoptosis in MCF-7 cells. The complexes of HSA-Dhc and HSA-DhcA were observed as
      static quenching, and the binding constants (K) was 4.7 +/- .03 * 104 M-1 and 3.9
      +/- .05 * 104 M-1, and their binding free energies were found to be -6.4 and 
      6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine
      1.4 +/- .05 * 104 M-1 replaced Dhc, and phenylbutazone 1.5 +/- .05 * 104 M-1
      replaced by DhcA, which explains domain I and domain II are the binding sites for
      Dhc and DhcA. Further, FT-IR, synchronous spectroscopy, and CD results revealed
      that the secondary structure of HSA was altered in the presence of Dhc and DhcA.
      Furthermore, the atomic force microscopy and transmission electron microscopy
      showed that the dimensions like height and molecular size of the HSA-Dhc and HSA
      DhcA complex were larger compared to HSA alone. Detailed analysis through
      molecular dynamics simulations also supported greater stability of HSA-Dhc and
      HSA-DhcA complexes, and root-mean-square-fluctuation interpreted the binding site
      of Dhc as domain IB and domain IIA for DhcA. This information is valuable for
      further development of steroid derivative with improved pharmacological
      significance as novel anti-cancer drugs.

PMID- 29375010
TI  - Aggressive systolic blood pressure control in older subjects: benefits and risks.
AB  - Systolic hypertension, especially isolated systolic hypertension (ISH) is very
      common in older subjects aged >= 65 years and is a major risk factor for
      cardiovascular disease (CVD), strokes, heart failure (HF) and chronic kidney
      disease (CKD). It is also, directly and linearly related with these complications
      irrespective of sex, or ethnicity, but it is worse with the advancement of age.
      Effective control of systolic blood pressure (SBP), is associated with
      significant reduction in the incidence of these complications. Currently, there
      is a debate about the optimal SBP control in view of the Systolic Blood Pressure
      Intervention Trial (SPRINT) showing beneficial cardiovascular (CV) effects of
      intensive SBP of < 120 mmHg in older patients. Also, the recently released blood
      pressure (BP) guidelines by the American College of Cardiology, the American
      Heart Association and the American Society of Hypertension (ACC/AHA/ASH)
      recommend a SBP reduction of < 130 mmHg. These SBP treatment recommendations are
      in contrast with the current (JNC VIII) committee of BP treatment guidelines,
      which recommend a SBP reduction < 150 mmHg for the same age of patients. All
      these different recommendations have created a debate regarding the optimal
      treatment targets for the systolic hypertension of the elderly patients. To gain
      more information a focused Medline search was conducted from 2010 to 2017 using
      the terms, systolic blood pressure, aggressive control, older subjects, treatment
      guidelines, and 37 pertinent papers were retrieved. The findings from these
      studies suggest a SBP reduction of < 140 mm Hg for persons aged >= 60 years, with
      an attempt for SBP reduction to <=130 mm Hg in healthier subjects and hose with
      CVD, DM, and CKD. Care should be taken not to further reduce the SBP in older
      subjects if their DBP is <=60 mmHg for the fear of J-curve effect.

PMID- 29375012
TI  - ASSA: Fast identification of statistically significant interactions between long
      RNAs.
AB  - The discovery of thousands of long noncoding RNAs (lncRNAs) in mammals raises a
      question about their functionality. It has been shown that some of them are
      involved in post-transcriptional regulation of other RNAs and form inter
      molecular duplexes with their targets. Sequence alignment tools have been used
      for transcriptome-wide prediction of RNA-RNA interactions. However, such
      approaches have poor prediction accuracy since they ignore RNA's secondary
      structure. Application of the thermodynamics-based algorithms to long transcripts
      is not computationally feasible on a large scale. Here, we describe a new
      computational pipeline ASSA that combines sequence alignment and thermodynamics
      based tools for efficient prediction of RNA-RNA interactions between long
      transcripts. To measure the hybridization strength, the sum energy of all the
      putative duplexes is computed. The main novelty implemented in ASSA is the
      ability to quickly estimate the statistical significance of the observed
      interaction energies. Most of the functional hybridizations between long RNAs
      were classified as statistically significant. ASSA outperformed 11 other tools in
      terms of the Area Under the Curve on two out of four test sets. Additionally, our
      results emphasized a unique property of the [Formula: see text] repeats with
      respect to the RNA-RNA interactions in the human transcriptome. ASSA is available
      at https://sourceforge.net/projects/assa/.

PMID- 29375011
TI  - Effect of the Japanese diet during pregnancy and lactation or post-weaning on the
      risk of metabolic syndrome in offspring.
AB  - We examined the effects on offspring of ingestion of the 1975 Japanese diet
      during pregnancy and lactation and after weaning in mice. Pregnant dams were
      divided into groups that were fed the Japanese diet or a control diet and raised
      until offspring were weaned. The offspring after weaning were further divided
      into groups that were raised on the Japanese diet or the control diet. Ingestion
      of the Japanese diet after weaning suppressed accumulation of visceral fat in
      offspring, and reduced the amount of lipids in serum and liver. This effect was
      weakened if the Japanese diet was only ingested during pregnancy and lactation.
      Therefore, it was suggested that ingestion of the Japanese diet of mothers during
      pregnancy and lactation weakens the lipid accumulation inhibitory effect of the
      Japanese diet in children.

PMID- 29375014
TI  - Impact of a formal pharmacist-run oral antineoplastic monitoring program: A pilot
      study in an adult genitourinary oncology clinic.
AB  - Background In recent years, there has been a changing paradigm in the management
      of oncologic disease states from the use of intravenous therapies, requiring a
      visit to the infusion center or hospitalization, to new therapies that can be
      administered orally.1,2 Several publications have evaluated the role pharmacists
      may play in the initial prescribing of oral chemotherapy, however the impact of a
      formalized pharmacist follow-up program has not been well defined. This study
      evaluates the impact of a pilot pharmacist-run oral antineoplastic monitoring
      program. Methods This retrospective cohort analysis evaluated patients prescribed
      an oral antineoplastic in the genitourinary oncology clinic at an academic
      medical center between 1 July 2014 and 15 March 2017. Patients enrolled in the
      program were compared to a historical control group. The primary objective was
      adherence to pre-defined standards for monitoring. Secondary objectives include
      persistence on therapy, need to seek medical care, analysis of pharmacist
      interventions, patient satisfaction, and financial impact for the on-site retail
      pharmacy. Results In total, 33 patients were evaluated (11 cases, 22 controls).
      Average adherence to monitoring recommendations was significantly higher in the
      case group compared to controls (89% vs. 61%; p = 0.008). In total, 67
      interventions were made by the clinical pharmacist with an average of 6 per
      patient. Conclusions This study shows that formalized pharmacist follow-up
      programs can improve patients' adherence with antineoplastic monitoring
      standards. Additionally, pharmacists made clinically significant interventions
      and had high patient satisfaction, providing justification for expansion into
      other disease states.

PMID- 29375013
TI  - Comparison of visual and auditory emotion recognition in patients with cerebellar
      and Parkinson's disease.
AB  - Widespread cortical-subcortical networks are involved in the recognition and
      discrimination of emotional contents of facial and vocal expression, whereby the
      cerebellum and basal ganglia are two subcortical regions implicated in these
      networks with limited evidence to their specific contributions. To investigate
      this we compared patients with circumscribed cerebellar lesions and patients with
      Parkinson's disease (PD) on an approved test battery. We studied two groups with
      subcortical disease, focal cerebellar infarction (n = 22) and PD (n = 22), and a
      neurological control group with focal supratentorial ischemia (SI) (n = 16) were.
      Assessments were according to inpatient protocols for neuropsychological routine
      evaluation, including tests of memory, executive function and attention.
      Participants completed the Tuebingen Affect Battery, a recognized measure of
      recognition and discrimination of facial and vocal expression of emotion. As a
      result, cerebellar lesions were associated with greater impairment than PD and SI
      in recognition and discrimination of cues of both facial and vocal expressions of
      differing basic emotions. No confounding effect of other cognitive domains,
      particularly executive function and attention, was found. Taken together, our
      findings suggest a specific contribution of the cerebellum to cerebral networks
      that process facial and vocal emotion expression, related to rapid decisions
      regulating appropriate behavioral responses in social environments.

PMID- 29375015
TI  - How can the use of closed system transfer devices to facilitate sharing of drug
      vials be optimised to achieve maximum cost savings?

PMID- 29375016
TI  - Exploring the binding interaction of calf thymus DNA with lapatinib, a tyrosine
      kinase inhibitor: multi-spectroscopic techniques combined with molecular docking.

PMID- 29375017
TI  - Maternal protein malnutrition induces autism-like symptoms in rat offspring.
AB  - OBJECTIVE: We tested the correlation between maternal protein malnutrition and
      autistic-like symptoms using behavioral tests in rodents that measure main
      behavioral characteristics observed in humans with autism spectrum disorder
      (ASD). METHODS: Pregnant female rats were fed a normal diet or a hypoproteic diet
      during gestation and lactation periods. The litters were weighed every 3 days
      during lactation, and the offspring were tested in behavioral tasks during
      infancy (postnatal day (PND) 5: quantification of ultrasonic vocalizations; PND
      13: homing behavior test) and adolescence (PND 30-32: open field, hole-board,
      play social behavior, and object recognition tests) in order to capture the
      prevalence of some of the core and associated symptoms of ASD. RESULTS: Litters
      of the hypoproteic diet group had a lesser weight gain during lactation. In
      addition, pups of dams fed with a hypoproteic diet vocalized less compared to
      those fed with a normal diet, and they showed impaired social discrimination
      abilities in the homing behavior test. In adolescence, both male and female
      offspring of the hypoproteic diet group showed no impairment in locomotor
      activity; however, they exhibited stereotypic behavior in the hole-board test and
      a decrease in social play behaviors. Male offspring showed increased interest in
      exploring a familiar object rather than a novel object. CONCLUSION: Our results
      show that maternal protein malnutrition in rats causes offspring behaviors that
      resemble core and associated ASD symptoms.

PMID- 29375018
TI  - Comparison of small intestinal submucosa and polypropylene mesh for abdominal
      wall defect repair.
AB  - Abdominal wall defects are a common medical problem, and inadequate repair
      methods can lead to serious complications. Abdominal wall reconstruction using
      autologous tissue, or non-biological, biological, or composite patches is often
      performed to repair defective areas. In particular, composite patches containing
      both polymeric and biological materials have gained increasing attention due to
      their good mechanical properties and biocompatibility. However, it is still
      unclear whether the quality of repairs using composite patches is superior to
      that of a biological patch. Based on the limitations of previous studies, we
      compared small intestinal submucosa (SIS) patches with SIS + polypropylene mesh
      (PPM) patches for repairing abdominal wall defects in adult beagle dogs. Forty
      five female dogs were subjected to surgical resection to produce abdominal wall
      defects. SIS or SIS + PPM was used as patch for the defects. Morphology,
      biomechanics, and histological evaluations were performed to evaluate the
      efficacy and safety of such therapies. Our findings demonstrated that SIS had
      advantages over SIS + PPM considering biological activity and histocompatibility
      without increasing the risk of repair failure.

PMID- 29375019
TI  - Endocervicoscopy and Biopsy to Detect Cervical Intraepithelial Squamous Neoplasia
      in Nonvisible Squamocolumnar Junction With Unsatisfactory Colposcopy: A Pilot
      Study.
AB  - The aim of this study was to investigate the practical utility of
      endocervicoscopy and targeted biopsy in high-risk human papilloma virus-positive
      women with abnormal squamous cells on cervical cytology and unsatisfactory
      colposcopy with nonvisible squamocolumnar junction. Seventy-seven high-risk human
      papilloma virus-positive patients with abnormal cervical cytology for squamous
      cells bearing type 3 transformation zone were enrolled. Endoscopic examination of
      the endocervical epithelium, with office-based continuous-flow hysteroscopy after
      application of acetic acid 5%, followed by targeted biopsies and consequent large
      loop excision of the transformation zone was carried out. Sensitivity,
      specificity, positive predictive value and negative predictive value of
      endocervicoscopy, and orientated biopsy were confronted with the results of large
      loop excision of the transformation zone (referral test). The sensitivity and
      specificity of endocervicoscopy and orientated biopsy for low-grade cervical
      intraepithelial neoplasia were 53% and 81%, respectively, while the sensitivity
      and specificity for high-grade cervical intraepithelial neoplasia were 64% and
      47%, respectively. The positive predictive value for low-grade cervical
      intraepithelial neoplasia was 64% and for high-grade cervical intraepithelial
      neoplasia was 88%. The negative predictive value for low-grade cervical
      intraepithelial neoplasia was 87% and for high-grade cervical intraepithelial
      neoplasia was 41%. Endocervicoscopy is a safe, office-based technique. It is a
      reliable method to detect the transformation zone in patients with type 3
      transformation zone and unsatisfactory colposcopy. It potentially allows target
      biopsy of the transformation zone but presents a relatively low
      specificity/negative predictive value to predict high-grade cervical
      intraepithelial neoplasia, thus negative biopsy results should be interpreted
      with caution.

PMID- 29375021
TI  - Comparative analysis of waste-to-energy alternatives for a low-capacity power
      plant in Brazil.
AB  - The Brazilian National Solid Waste Policy has been implemented with some
      difficulty, especially in convincing the different actors of society about the
      importance of conscious awareness among every citizen and businesses concerning
      adequate solid waste disposal and recycling. Technologies for recovering energy
      from municipal solid waste were considered in National Solid Waste Policy (NSWP),
      given that their technical and environmental viability is ensured, being the
      landfill biogas burning in internal combustion engines and solid waste
      incineration suggested options. In the present work, an analysis of current
      technologies and a collection of basic data on electricity generation using
      biogas from waste/liquid effluents is presented, as well as an assessment of the
      installation of a facility that harnesses biogas from waste or liquid effluents
      for producing electricity. Two combined cycle concepts were evaluated with
      capacity in the range 4-11 MW, gas turbine burning landfill biogas and an
      incinerator that burns solid waste hybrid cycle, and a solid waste gasification
      system to burn syngas in gas turbines. A comparative analysis of them
      demonstrated that the cycle with gasification from solid waste has proved to be
      technically more appealing than the hybrid cycle integrated with incineration
      because of its greater efficiency and considering the initially defined
      guidelines for electricity generation. The economic analysis does not reveal
      significant attractive values; however, this is not a significant penalty to the
      project given the fact that this is a pilot low-capacity facility, which is
      intended to be constructed to demonstrate appropriate technologies of energy
      recovery from solid waste.

PMID- 29375022
TI  - Do tetracyclines have the potential to reduce the risk of Clostridium difficile
      infection?

PMID- 29375020
TI  - Novel Cancer Stem Marker and Its Applicability for Grading Primary Human Gliomas.
AB  - Poorly differentiated cell populations including tumor-initiating stem cells have
      been demonstrated to display a unique ability to natively internalize fragmented
      double-stranded DNA. Using this feature as a marker, we show that 0.1% to 6% of
      human glioblastoma cells from the bioptates can effectively internalize a
      fluorescently labeled DNA probe. Of these, using samples from 3 patients, 66% to
      100% cells are also positive for CD133, a well-established surface marker of
      tumor-initiating glioma stem cells. Using the samples from primary malignant
      brain lesions (33 patients), we demonstrate that tumor grading significantly
      correlates ( R = .71) with the percentage of DNA-internalizing cells. No such
      correlation is observed for relapse samples (18 patients).

PMID- 29375023
TI  - Understanding Diabetes-Related Distress Characteristics and Psychosocial Support
      Preferences of Urban African American Adults Living With Type 2 Diabetes: A Mixed
      Methods Study.
AB  - Purpose The purpose of this study is to understand diabetes-related distress
      (DRD) characteristics and identify psychosocial support preferences of urban
      African American adults living with type 2 diabetes (T2DM). Methods A 2-phase,
      mixed-methods sequential explanatory study design was used to gather data. In
      phase 1, a purposive sample of participants (N = 155) was recruited and asked to
      complete a written survey. The Diabetes Distress Scale (DDS17) was used to assess
      DRD, including subscales-emotional burden (EB), regimen distress (RD),
      interpersonal distress (ID), and physician distress (PD). In phase 2, a subset of
      phase 1 participants (N = 23) volunteered to attend 1 of 4 gender-stratified
      follow-up focus groups to contextualize the quantitative survey results. Results
      Survey findings indicate that on average, participants had moderate levels of DRD
      (aggregate), RD, and EB but had low ID and PD. During follow-up focus groups,
      participants described RD and EB as their primary distress types and emphasized
      that clinicians should prioritize the mental health aspects of T2DM similarly to
      its physical aspects. Participants expressed a desire for culturally appropriate
      peer support groups as a psychosocial support resource for distress coping and
      specifically requested the development of gender-stratified groups and groups for
      young adults. Conclusions Results support the need to screen for and address
      diabetes-related distress among African American patients with T2DM. Findings
      also inform the development of culturally appropriate psychosocial support
      resources to facilitate diabetes-related distress coping.

PMID- 29375024
TI  - Considerations of how to conduct meta-analyses in psychological interventions.

PMID- 29375025
TI  - Comparison of Nostocean hormogonium induction and its motility on solid plates
      between agar and gellan gum at varying gel matrix concentrations.
AB  - To establish a sensitive bioassay for Nostocean hormogonium induction, we
      compared the effectiveness of the morpho-differentiation induction on two gelled
      plates, agar and gellan gum, for anacardic acid C15:1-Delta8 decyl ester (1) (100
      nmol/disc). On BG-110 (nitrogen-free) medium-based 0.6 and 0.8% agar plates,
      Nostoc sp. strain Yaku-1 isolated from a coralloid root of Cycas revoluta in
      Yakushima Island showed clear morpho-differentiation from filamentous aggregates
      into hormogonia, and the induced hormogonia dispersed within 24 h; however,
      similar hormogonium formation was not observed at agar concentrations of 1.0% or
      higher. Conversely, hormogonium induction was considerably more pronounced on
      gellan gum plates than those on agar plates through concentrations ranging from
      0.6 to 1.6% even after 12 h of incubation, particularly active on the 0.8-1.0%
      gellan gum plates. Thus, gellan gum plates can achieve clear results within 12 h
      and are thus highly useful for primary screening for hormogonium-inducing factors
      (HIFs).

PMID- 29375026
TI  - Psychometric Evaluation of the Social Phobia Inventory and the Mini-Social Phobia
      Inventory in a Swedish University Student Sample.
AB  - Social anxiety is common in the general population, as well as among students in
      higher education. For screening of social anxiety, there is a need for brief
      scales. In the present study, the psychometric properties were examined in a
      Swedish version of the Social Phobia Inventory (SPIN) and the Mini-Social Phobia
      Inventory (Mini-SPIN) in a university student sample ( n = 161). In addition to
      the SPIN and Mini-SPIN, participants completed measures of fear of public
      speaking, general anxiety, depression, and quality of life. Exploratory factor
      analyses were used to investigate the underlying dimensions of the SPIN, and
      reliability, convergent, and divergent validity of SPIN and Mini-SPIN were
      examined by Cronbach's alpha and correlation analyses. It was found that a
      shorter eight-item version of the SPIN was associated with two solid factors (
      fear and avoidance of social interaction and fear and avoidance of criticism),
      and acceptable internal consistency, convergent, and divergent validity. In
      addition, the Mini-SPIN was associated with satisfactory convergent validity, but
      the reliability was not acceptable. It is concluded that the SPIN-8 is a viable
      screening tool for social anxiety in a university student population.

PMID- 29375027
TI  - Women and Self-Promotion: A Test of Three Theories.
AB  - Although self-promotion (communicating one's past accomplishments and positive
      characteristics) is important for obtaining career and educational opportunities,
      women feel uncomfortable when doing it, which limits their self-promotion
      success. This study tested which of the three possible theoretical mechanisms
      explained women's limited self-promotion success: (1) cognitive dissonance, (2)
      stereotype threat, and (3) backlash avoidance. In this experiment, college women
      ( N = 123) wrote a scholarship application essay and the ownership of the essay
      was varied experimentally. The essays were evaluated by the authors themselves
      and independent judges. The results were most consistent with a backlash
      avoidance mechanism whereby women feel uncomfortable self-promoting due to
      perceived social consequences.

PMID- 29375028
TI  - Investigating the Relationships Among Resilience, Social Anxiety, and
      Procrastination in a Sample of College Students.
AB  - This study investigated the relationships among resilience, social anxiety, and
      procrastination in a sample of college students. Specifically, structural
      equation modeling analyses were applied to examine the effect of resilience on
      procrastination and to test the mediating effect of social anxiety. The results
      of this study suggested that social anxiety partially mediated the relationship
      between resilience and procrastination. Students with higher levels of resilience
      reported a lower frequency of procrastination behavior, and resilience had an
      indirect effect on procrastination through social anxiety. The results of this
      study clarify the current knowledge of the mixed results on resilience and
      procrastination behaviors and offer practical learning strategies and
      psychological interventions.

PMID- 29375029
TI  - Saving for a Better Retirement: How Risk Attitudes Affect Choice of Retirement
      Scheme.
AB  - Over 3 million people in Hong Kong and 21 million people in the UK are saving for
      retirement under the mandatory provident fund and individual savings account
      schemes, respectively. Yet, we know little about how individual preferences, such
      as risk attitudes (risk-seeking and risk-averse) that are known to impact highly
      consequential decisions in a variety of real-world contexts, impact retirement
      investment choices. In two experimental studies (Study 1-Hong Kong sample and
      Study 2-United Kingdom sample), we show that personal risk attitudes were a
      strong predictor of the profile of retirement investment portfolios. Specially,
      risk-averse people allocated more of their savings to low-risk funds than risk
      seeking people. The pattern of findings is consistent in both Hong Kong mandatory
      and the UK voluntary retirement investment schemes. These findings are considered
      in light of policy decisions made in Hong Kong retirement and UK pension schemes.

PMID- 29375030
TI  - What Did You Expect? Substance Use Expectancies Mediate the Relationships Between
      Dark Triad Traits, Substance Use, and Substance Preference.
AB  - This study explores the role of substance use expectancies as mediators between
      the Dark Triad of personality, substance use, and substance use preferences. A
      sample of college students ( M = 19.38, SD = 2.63, N = 207) completed an online
      questionnaire that assessed the Dark Triad traits, substance use history,
      substance preferences, and substance use expectancies. Three specific substance
      use expectancies-increased confidence, tension reduction, and cognitive
      enhancement-were shown to either partially or fully mediate the relationships
      between the Dark Triad and substance use behaviors and preference for certain
      substances of abuse. These findings may hold clinical implications for the
      treatment of substance use disorders and further the understanding of factors
      contributing to the etiology and progression of substance abuse and substance use
      disorders.

PMID- 29375031
TI  - Unique antimicrobial spectrum of ophiobolin K produced by Aspergillus ustus.
AB  - A co-cultivation study of two fungal strains showed that Aspergillus ustus could
      inhibit Aspergillus repens growth. The bioactive compound responsible for the
      observed activity was purified and identified as a sesterterpene, ophiobolin K.
      Ophiobolin K exhibited marked inhibition against both fungi and bacteria,
      especially A. repens, A. glaucus and gram-positive bacteria including Bacillus
      subtilis, Staphylococcus aureus, and Micrococcus luteus.

PMID- 29375033
TI  - Chyloptysis with chylopericardium, a rare case and mini-review.
AB  - BACKGROUND: Chyloptysis is reflux of chyle into the lungs and is a rare
      manifestation of primary chylous disorders. CASE PRESENTATION: Over 29 months, on
      the basis of x-rays, a 33-year-old female was repeatedly misdiagnosed with
      recurrent right-sided pneumonia; her symptoms included a recurrent cough, the
      appearance of cheese-like sputum, and diffuse pulmonary exudates. There was a
      history that abundant fluid in the pericardium was confirmed with
      echocardiography to have been present and asymptomatic for 4 years.
      Lymphangiography and surgery confirmed that the terminal portion of the thoracic
      duct was compressed by thick fibrous tissue and the vascular sheath of the
      internal jugular vein. Chyloptysis caused by high peribronchial lymphatic
      pressure was diagnosed and surgical intervention relieved the symptoms.
      CONCLUSION: Chyloptysis is rare and easy to misdiagnose but is a typical symptom
      of chylous reflux syndrome.

PMID- 29375032
TI  - Incorporating Radiation Oncology into Immunotherapy: proceedings from the ASTRO
      SITC-NCI immunotherapy workshop.
AB  - Radiotherapy (RT) has been a fundamental component of the anti-cancer
      armamentarium for over a century. Approximately half of all cancer patients are
      treated with radiotherapy during their disease course. Over the two past decades,
      there has been a growing body of preclinical evidence supporting the
      immunomodulatory effects of radiotherapy, particularly when combined with
      immunotherapy, but only anecdotal clinical examples existed until recently. The
      renaissance of immunotherapy and the recent U.S. Food and Drug Administration
      (FDA) approval of several immune checkpoint inhibitors (ICIs) and other immuno
      oncology (IO) agents in multiple cancers provides the opportunity to investigate
      how localized radiotherapy can induce systemic immune responses. Early clinical
      experiences have demonstrated feasibility of this approach but additional
      preclinical and clinical investigation is needed to understand how RT and
      immunotherapy can be optimally combined.To address questions that are critical to
      successful incorporation of radiation oncology into immunotherapy, the American
      Society for Radiation Oncology (ASTRO), the Society for Immunotherapy of Cancer
      (SITC) and the National Cancer Institute (NCI) organized a collaborative
      scientific workshop, Incorporating Radiation Oncology into Immunotherapy, that
      convened on June 15 and 16 of 2017 at the Natcher Building, NIH Campus in
      Bethesda, Maryland. This report summarizes key data and highlights from each
      session.

PMID- 29375034
TI  - Diet/lifestyle and risk of diabetes and glycemic traits: a Mendelian
      randomization study.
AB  - BACKGROUND: Observational studies have demonstrated diet/lifestyle play roles in
      development of type 2 diabetes (T2DM); however, it remains unclear whether these
      relationships are causal. METHODS: A two-sample MR approach was used to examine
      the causal effect of diet/lifestyle upon risk of T2DM and glycemic traits.
      RESULTS: The protein intake-increasing allele C of FTO was significant associated
      with higher risk of T2DM (Beta +/- SE = 0.104 +/- 0.014, P = 4.40 * 10- 11),
      higher level of HOMA-IR (Beta +/- SE = 0.016 +/- 0.004, P = 9.55 * 10- 5), HOMA-B
      (Beta +/- SE = 0.008 +/- 0.003, P = 0.020). Using MR analyses, increased protein
      intake was causally associated with an increased risk of T2DM (Beta +/- SE =
      0.806 +/- 0.260, P = 0.002). In addition, smoking cessation was causally
      associated with increased levels of glycemic traits such as HOMA-IR (Beta +/- SE
      = 0.165 +/- 0.072, P = 0.021), fasting insulin (Beta +/- SE = 0.132 +/- 0.066, P
      = 0.047) and fasting glucose (Beta +/- SE = 0.132 +/- 0.064, P = 0.039).
      CONCLUSIONS: These results provide evidence supporting a causal role for higher
      protein intake and smoking cession in T2DM. Our study provides further rationale
      for individuals at risk for diabetes to keep healthy lifestyle.

PMID- 29375035
TI  - A feedback regulatory model for RifQ-mediated repression of rifamycin export in
      Amycolatopsis mediterranei.
AB  - BACKGROUND: Due to the important role of rifamycin in curing tuberculosis
      infection, the study on rifamycin has never been stopped. Although RifZ, which
      locates within the rifamycin biosynthetic cluster, has recently been
      characterized as a pathway-specific regulator for rifamycin biosynthesis, little
      is known about the regulation of rifamycin export. RESULTS: In this work, we
      proved that the expression of the rifamycin efflux pump (RifP) was regulated by
      RifQ, a TetR-family transcriptional regulator. Deletion of rifQ had little impact
      on bacterial growth, but resulted in improved rifamycin production, which was
      consistent with the reverse transcription PCR results that RifQ negatively
      regulated rifP's transcription. With electrophoretic mobility shift assay and
      DNase I Footprinting assay, RifQ was found to directly bind to the promoter
      region of rifP, and a typical inverted repeat was identified within the RifQ
      protected sequences. The transcription initiation site of rifP was further
      characterized and found to be upstream of the RifQ binding sites, well explaining
      the RifQ-mediated repression of rifP's transcription in vivo. Moreover, rifamycin
      B (the end product of rifamycin biosynthesis) remarkably decreased the DNA
      binding affinity of RifQ, which led to derepression of rifamycin export, reducing
      the intracellular concentration of rifamycin B as well as its toxicity against
      the host. CONCLUSIONS: Here, we proved that the export of rifamycin B was
      repressed by RifQ in Amycolatopsis mediterranei, and the RifQ-mediated repression
      could be specifically relieved by rifamycin B, the end product of rifamycin
      biosynthesis, based on which a feedback model was proposed for regulation of
      rifamycin export. With the findings here, one could improve the antibiotic yield
      by simply inactivating the negative regulator of the antibiotic transporter.

PMID- 29375037
TI  - The Unforgettables: a chorus for people with dementia with their family members
      and friends.
AB  - Summary/AbstractOur experience evaluating a museum program for people with
      dementia together with their family members demonstrated benefits for all
      participants. We hypothesized that participation in a chorus would also have
      positive effects, giving them an opportunity to share a stimulating and social
      activity that could improve their quality of life. We inaugurated a chorus for
      people with dementia and their family caregivers in 2011, which rehearses and
      performs regularly. Each person with dementia must be accompanied by a friend or
      family member and must commit to attending all rehearsals and the concert that
      ensues. A pilot study included a structured assessment, take home questionnaires
      and focus groups. Analyses of pre-post scores were conducted; effect size was
      quantified using Cohen's d. Results showed that quality of life and communication
      with the other member of the dyad improved (Effect size: Cohen's d between 0.32
      and 0.72) for people with dementia; quality of life, social support,
      communication and self-esteem improved (d between 0.29 and 0.68) for caregivers.
      Most participants stated that benefits included belonging to a group, having a
      normal activity together and learning new skills. Participants attended
      rehearsals in spite of harsh weather conditions. The chorus has been rehearsing
      and performing together for more than 6 years and contributing to its costs.
      Results of this pilot study suggest that people in the early to middle stage of
      dementia and their family members and friends can enjoy and learn from rehearsing
      and performing in concerts that also engage the wider community. It is essential
      to conduct additional larger studies of the benefits of participating in a
      chorus, which may include improved quality of life and social support for all,
      and reduced cognitive decline among people with dementia.

PMID- 29375038
TI  - The amyotrophic lateral sclerosis supportive care needs assessment instrument:
      Development and psychometric evaluation.
AB  - OBJECTIVE: The aim of the study is to develop an amyotrophic lateral sclerosis
      supportive care needs (ALSSCN) instrument based on Fitch's Supportive Care Needs
      Framework and to test its psychometric properties. METHOD: This study consists of
      three parts: (1) item generation from the literature review and qualitative
      interview; (2) content validation; and (3) psychometric evaluation of the
      instrument. Participants who were diagnosed with ALS (n = 139) were recruited
      from two ALS clinics in Seoul, Korea, and Busan, Korea for the psychometric
      testing. Result The ALSSCN consisted of 37 items with seven domains: physical,
      psychological, emotional, spiritual, social, informational, and practical needs.
      The Cronbach's alpha of each domain ranged from 0.61 (social needs) to 0.90
      (emotional needs). The intra-class correlation coefficient for test-retest was
      0.89, indicating good test-retest reliability. The overall ALSSCN was
      significantly negatively correlated with the quality of life, which supported
      convergent validity. Confirmatory factor analysis of the ALSSCN supported a seven
      factor model. Significance of results The ALSSCN has acceptable internal
      consistency, stability, and content and construct validity in a Korean ALS
      population. ALSSCN is a psychometrically sound measure and can be adopted by
      healthcare professionals, researchers, and administrators to comprehensively
      assess the perceived supportive care needs of patients with ALS.

PMID- 29375039
TI  - Induced pluripotent stem cells in modeling and cell-based therapy of amyotrophic
      lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized
      by neuromuscular degeneration and the progressive loss of upper and lower motor
      neurons (MNs), causing weakness and paralysis. However, the underlying mechanisms
      of this disease are still unknown and there is no cure, or even treatment to stop
      or reverse its pathology. Consequently, most ALS patients die within 3 - 5 years
      after disease onset. While considerable progress has been made in studying animal
      models of ALS, they lack clinical suitability due to genetic differences.
      However, the recent development of induced pluripotent stem cells (iPSCs) has
      made it possible to study human disease-specific neuronal and glial cells to
      identify disease mechanisms and develop phenotypic screens for drug discovery.
      iPSCs provide researchers with a model of naturally occurring pathology under the
      human genetic background and MNs differentiated from human iPSCs bearing ALS
      associated mutations offer a powerful model to study disease pathology. This
      paper reviews recent methods of differentiating iPSCs into neuronal cells and
      suggests further applications of these iPSCs-derived cells for ALS disease
      modeling, drug screening, and possible cell-based therapy.

PMID- 29375040
TI  - Melatonin, advanced oxidation protein products and total antioxidant capacity as
      seminal parameters of prooxidant-antioxidant balance and their connection with
      expression of metalloproteinases in context of male fertility.
AB  - Currently, in highly developed, industrialized countries male factors are
      identified as the primary cause of infertility in about 60% of childless couples.
      Standard semen analysis parameters, such as sperm morphology, number and
      motility, are important in predicting the fertility of large populations, but
      they are not sufficient to fully specify a particular donor sperm's ability to
      fertilize the egg. The semen also comprises components, which may also affect
      sperm fertilizing ability and which have thus far remained little explored: the
      biochemical parameters of the seminal plasma secreted by the testis, the
      seminiferous tubules and the prostate gland, such as: matrix metalloproteinases
      (MMP-2 and MMP-9) and their specific tissue inhibitors (TIMP-1 and TIMP-2). We
      highlight the need for a better determination of prooxidant-antioxidant balance
      parameters such as: melatonin, advanced oxidation protein products (AOPPs) and
      total antioxidant capacity (TAC) in human semen when establishing the diagnostics
      of male subfertility or infertility. We also discuss their connection with
      seminal plasma metalloproteinases and their inhibitors. In particular, we believe
      that the cumulative and synergic effects of the sperm redox parameters on male
      fertility need to be better explored and we suggest that they should be studied
      in conjunction with other biologically active parameters of the ejaculate such as
      the expression of metalloproteinases and their tissue inhibitors. This will
      enable a better understanding of how their correlated effects impact semen
      condition.

PMID- 29375036
TI  - Rotavirus vaccine impact and socioeconomic deprivation: an interrupted time
      series analysis of gastrointestinal disease outcomes across primary and secondary
      care in the UK.
AB  - BACKGROUND: Rotavirus causes severe gastroenteritis in infants and young children
      worldwide. The UK introduced the monovalent rotavirus vaccine (Rotarix(r)) in
      July 2013. Vaccination is free of charge to parents, with two doses delivered at
      8 and 12 weeks of age. We evaluated vaccine impact across a health system in
      relation to socioeconomic deprivation. METHODS: We used interrupted time-series
      analyses to assess changes in monthly health-care attendances in Merseyside, UK,
      for all ages, from July 2013 to June 2016, compared to predicted counterfactual
      attendances without vaccination spanning 3-11 years pre-vaccine. Outcome measures
      included laboratory-confirmed rotavirus gastroenteritis (RVGE) hospitalisations,
      acute gastroenteritis (AGE) hospitalisations, emergency department (ED)
      attendances for gastrointestinal conditions and consultations for infectious
      gastroenteritis at community walk-in centres (WIC) and general practices (GP).
      All analyses were stratified by age. Hospitalisations were additionally
      stratified by vaccine uptake and small-area-level socioeconomic deprivation.
      RESULTS: The uptake of the first and second doses of rotavirus vaccine was 91.4%
      (29,108/31,836) and 86.7% (27,594/31,836), respectively. Among children aged < 5
      years, the incidence of gastrointestinal disease decreased across all outcomes
      post-vaccine introduction: 80% (95% confidence interval [CI] 70-87%; p < 0.001)
      for RVGE hospitalisation, 44% (95% CI 35-53%; p < 0.001) for AGE
      hospitalisations, 23% (95% CI 11-33%; p < 0.001) for ED, 32% (95% CI 7-50%; p =
      0.02) for WIC and 13% (95% CI -3-26%; p = 0.10) for GP. The impact was greatest
      during the rotavirus season and for vaccine-eligible age groups. In adults aged
      65+ years, AGE hospitalisations fell by 25% (95% CI 19-30%; p < 0.001). The pre
      vaccine risk of AGE hospitalisation was highest in the most socioeconomically
      deprived communities (adjusted incident rate ratio 1.57; 95% CI 1.51-1.64; p <
      0.001), as was the risk for non-vaccination (adjusted risk ratio 1.54; 95% CI
      1.34-1.75; p < 0.001). The rate of AGE hospitalisations averted per 1,000 first
      doses of vaccine was higher among infants in the most deprived communities
      compared to the least deprived in 2014/15 (28; 95% CI 25-31 vs. 15; 95% CI 12-17)
      and in 2015/16 (26; 95% CI 23-30 vs. 13; 95% CI 11-16). CONCLUSIONS: Following
      the introduction of rotavirus vaccination, incidence of gastrointestinal disease
      reduced across the health-care system. Vaccine impact was greatest among the most
      deprived populations, despite lower vaccine uptake. Prioritising vaccine uptake
      in socioeconomically deprived communities should give the greatest health benefit
      in terms of population disease burden.

PMID- 29375041
TI  - Chronic orexin-A (hypocretin-1) treatment of type 2 diabetic rats improves
      glucose control and beta-cell functions.
AB  - Orexin regulates food intake and energy expenditure. Here, we test the ability of
      orexin-A (OXA, hypocretin-1) at improving metabolic control in type 2 diabetic
      animals and elaborate potential mechanisms of action. Rats with experimentally
      induced type 2 diabetes by a combination of streptozotocin injection and high-fat
      diet feeding were chronically infused with OXA. In vitro experiments were
      conducted on isolated pancreatic islets, primary adipocytes and insulin secreting
      INS-1E cells. OXA improved glucose control, enhanced insulin sensitivity and
      attenuated pancreatic beta-cell loss in type 2 diabetic rats. Ex vivo, apoptotic
      death of pancreatic islets isolated from OXA-treated type 2 diabetic animals as
      well as the impairment of glucose-stimulated insulin secretion were attenuated,
      as compared to islets derived from vehicle-treated rats. OXA reduced plasma tumor
      necrosis factor-alpha (TNF-alpha) and non-esterified fatty acids (NEFA) levels in
      type 2 diabetic rats. OXA decreased palmitate- and TNF-alpha-induced apoptosis of
      INS-1E cells. OXA improves glucose control by enhancing insulin sensitivity and
      protecting beta-cells from apoptotic cell death in type 2 diabetic animals.

PMID- 29375042
TI  - Effect of bone morphogenetic protein-15 on gonadotropin-stimulated synthesis of
      hyaluronan and progesterone in porcine ovarian follicle.
AB  - Bone morphogenetic protein-15 (BMP-15), an oocyte-derived growth factor, has been
      shown to play integral roles in regulation of ovarian follicular function in
      mammals. Despite the recognition of the physiological importance of the BMP
      system in regulation of gonadotropin action in the ovary, molecular mechanisms of
      BMP-15 effect on oocyte and somatic follicular cell functions remain poorly
      understood. The objective of this study was to determine the effect of BMP-15 on
      the FSH/LH-stimulated synthesis of hyaluronan (HA) by oocyte cumulus complexes
      (OCC) and progesterone by OCC and granulosa cells (GC) in the presence or absence
      of serum using primary porcine cultures. In addition, the effect of BMP-15 on
      oocyte maturation- and steroidogenesis-related transcripts after 4, 8, 16, and 24
      hours of cultivation was evaluated using real-time RT-PCR. We demonstrated that
      the FSH/LH-induced cumulus expansion was accompanied by a significant increase in
      CD44, PTGS2, CYP11A1 (at 4 h) and AREG, HAS2, TNFAIP6, STAR (at 8 h) mRNAs. While
      FSH/LH-stimulated total HA synthesis by OCC was not affected by BMP-15 in serum
      supplemented medium, its retention within the complex was significantly increased
      after the action of BMP-15 in comparison to FSH/LH alone (P < 0.001; 65% versus
      35%, respectively). Moreover, we detected a significant increase in the
      expression of AREG and TNFAIP6 (both at 16 h), and CYP11A1 (at 24 h) in FSH/LH
      stimulated OCC due to the action of BMP-15 compared to complexes cultured only
      with FSH/LH. In the presence of serum, BMP-15 markedly increased FSH/LH
      stimulated progesterone secretion by OCC (about 69%) and induced a significant
      decrease in FSH/LH-induced progesterone release by GC (about 35%) compared to
      FSH/LH alone. The present results indicate that the addition of BMP-15 to the
      gonadotropin-stimulated OCC cultured in serum-supplemented medium might improve
      oocyte-cumulus maturation.

PMID- 29375043
TI  - Influence of preterm delivery on ghrelin and obestatin concentrations in maternal
      plasm, milk and their expression in mammary epithelial cells.
AB  - Ghrelin and obestatin are gastrointestinal peptides with a potential role in the
      programming of metabolism in newborns. The present study aimed to investigate the
      influence of preterm delivery on ghrelin and obestatin concentrations in the
      maternal blood plasma and breast milk as well as their gene expressions in the
      mammary epithelial cells (MECs). On the 3rd day after delivery, milk and plasma
      samples were collected from mothers that carried to term or gave birth
      prematurely (< 36 weeks of gestation) and analyzed for ghrelin and obestatin
      concentrations. MECs isolated from the milk were analyzed for the relative
      expression of GHRL splice variants. In both groups ghrelin concentrations were
      significantly lower in milk than in blood plasma. In the preterm group obestatin
      concentrations were significantly higher in milk than in blood plasma but
      significantly lower in comparison to that of the control mothers. The expression
      of GHRL mRNAs was higher (P < 0.05) in MECs isolated from the preterm group as
      compared to those isolated from control mothers. The concentration of obestatin
      (but not ghrelin) in the breast milk is dependent on the term of pregnancy.
      Moreover, the lactating mammary gland is one of the sources of ghrelin and
      obestatin.

PMID- 29375044
TI  - Quantification of selected elements in ovarian tumours and their potentials as a
      tissue classifier.
AB  - Neoplastic and healthy ovarian tissues were analysed to identify the changes in
      the spatial distribution and concentration of elements using synchrotron induced
      micro X-ray fluorescence spectroscopy. High-resolution distribution maps of minor
      and trace elements were drawn. Significant amounts of elements such as P, S, Cl,
      K, Ca, Fe, Cu, Zn, Br and Rb were present in all neoplastic tissues analysed. The
      study showed significant diversifications in elemental distributions depending on
      the structure of tissue. The efficacy of micro X-ray fluorescence spectroscopy to
      distinguish between various types of ovarian tumours based on the concentrations
      of studied elements was confirmed by multivariate discriminant analysis. Our
      analysis showed that the most important elements for tissue classification are S,
      Cl, K, Fe, Zn, Br and Rb.

PMID- 29375045
TI  - Increased gene expression of selected vesicular and glial glutamate transporters
      in the frontal cortex in rats exposed to voluntary wheel running.
AB  - Though positive effects of exercise on mood and well being are well recognised,
      the central regulatory mechanisms are still not fully understood. The present
      study was aimed to testing the hypothesis that voluntary wheel running activates
      the gene expression of glutamate transporters in the brain cortex of rats. The
      animals were assigned to the control and voluntary wheel running groups.
      Voluntary wheel running rats had free access to a stainless steel activity wheel
      for 3 weeks. The daily running distance gradually increased to 6.21 +/- 1.05 km
      by day 21. Vesicular glutamate transporter 3 (VGLUT3) mRNA levels in the frontal
      cortex were significantly elevated in the group of running animals compared to
      the values in sedentary controls, while the expression of other vesicular
      transporters were unchanged. The concentrations of mRNA coding for glial
      glutamate transporter 1 (GLT-1), but not glutamate aspartate transporter (GLAST)
      were increased by running. Voluntary wheel running resulted in an elevation of
      plasma corticosterone and increased expression of brain derived neurotrophic
      factor (BDNF) in the frontal cortex. In conclusion, chronic voluntary wheel
      running results in increased gene expression of VGLUT3 and GLT-1 in the brain
      cortex without changes in other glutamate transporter subtypes.

PMID- 29375046
TI  - One session of exercise regulates cathepsin B activity in the livers of trained
      and untrained rats.
AB  - Physical exercise causes adaptive changes, mainly in muscles, but it also
      influences other organs, including liver. Most changes are beneficial; however,
      strenuous exercise is a strong stressor, and it can result in splanchnic
      hypoperfusion with subsequent disturbances in liver homeostasis and energy.
      Cathepsin B is a protease linked to protein turnover and extracellular matrix
      degradation. It is also involved in autophagy and the activation of
      proinflammatory and profibrotic pathways. This study investigated the influences
      of one session of exercise and endurance training on the mRNA, protein level, and
      activity of cathepsin B in rat liver. Healthy rats were randomly divided into two
      groups (n = 30, each); one group was untrained and the other received 6-weeks of
      endurance training with an increasing load. For each group, rats were sacrificed
      before (controls, n = 10), immediately after (n = 10), and 3 h after (n = 10) an
      acute bout of intense exercise. Liver gene expression was evaluated with
      quantitative real-time PCR. Liver protein content was measured with ELISA. Liver
      enzyme activity was measured fluorometrically. One session of exercise or
      training did not influence cathepsin B gene expression or protein concentration
      at any investigated time point. In untrained rats, cathepsin B activity decreased
      3 hours after (P = 0.027) one session of exercise. In trained rats, cathepsin B
      activity increased immediately (P = 0.005) after one session of exercise.
      Training did not influence baseline cathepsin B activity. In conclusion, one
      session of exercise differentially influenced cathepsin B activity in the liver,
      depending on training status.

PMID- 29375047
TI  - Effects of tadalafil (PDE5 inhibitor) and roflumilast (PDE4 inhibitor) on airway
      reactivity and markers of inflammation in ovalbumin-induced airway
      hyperresponsiveness in guinea pigs.
AB  - Selective phosphodiesterase (PDE) 4 inhibitors have recently been introduced into
      the therapy of chronic obstructive pulmonary disease. However, suppression of
      airway reactivity and eosinophilic inflammation by increased intracellular cAMP
      could be beneficial in bronchial asthma as well. PDE5 inhibitors are used for the
      therapy of erectile dysfunction, pulmonary hypertension, and other cardiovascular
      diseases, but an expression of PDE5 in several immune cells suggests its
      perspectives in inflammation, as well. To bring a new information on the
      therapeutically relevant potential of PDE4 and PDE5 inhibitors in allergic
      inflammation, this study evaluated the effects of 7-days administration of PDE5
      inhibitor tadalafil and PDE4 inhibitor roflumilast in experimentally-induced
      allergic inflammation and compared their action with effects of a corticosteroid
      dexamethasone. In the study, male adult guinea pigs were used. Control group was
      non-sensitized, while other animals were ovalbumin-sensitized over two weeks and
      thereafter treated intraperitoneally for 7 days with tadalafil or roflumilast
      (daily dose 1.0 mg/kg b.w. each), with their combination (0.5 mg/kg b.w. each),
      with dexamethasone (1.0 mg/kg b.w.), or with vehicle. Both tadalafil and
      roflumilast reduced the specific airway resistance after nebulization of
      histamine (a marker of in vivo airway reactivity), and decreased the in vitro
      airway reactivity to cumulative doses of histamine and acetylcholine in tracheal
      strips (significant for roflumilast) and in lung tissue strips (significant for
      both agents), analyzed by organ bath method. These changes were associated with
      decreased numbers of circulating leukocytes and eosinophils and lower production
      of interleukins 4 and 5, nuclear factor kappa B and tumor necrosis factor alpha
      in the lung. Similar effects were observed also for dexamethasone. Roflumilast
      and tadalafil, but not their combination with reduced doses, lowered lung TBARS,
      a marker of lipid oxidation. Selective PDE5 inhibition alleviated allergic airway
      inflammation, but it was less potent than PDE4 inhibition, whereas anti
      inflammatory action of the PDE inhibitors was comparable to the effects of
      dexamethasone.

PMID- 29375048
TI  - Effect of tachycardia on mRNA andf protein expression of the principal components
      of the lipolytic system in the rat's heart ventricles.
AB  - There is a convincing piece of evidence showing that most of free fatty acids
      (FFA) entering cardiomyocytes are first esterified into triacylglycerols (TG)
      before being oxidized or used for synthesis of complex lipids. The enzyme adipose
      triglyceride lipase (ATGL) initiates lipolysis of TG by hydrolyzing the first
      ester bond of the compound. As a result, free fatty acid and diacylglycerol (DG)
      are released in that process. Finally, DG may be further hydrolyzed by the enzyme
      hormone sensitive lipase (HSL). The aim of the present study was to examine
      effect of tachycardia on mRNA and protein expression of ATGL, CGI-58 (an
      activator of ATGL), G0S2 (an inhibitor of ATGL) and HSL in the left and right
      ventricle of the rat. The experiments were carried out on male Wistar rats, 240 -
      260 grams of body weight. After anesthesia, two electrodes were inserted in the
      right jugular vein and connected to SC-04 stimulator. The rats were randomly
      allocated into one of the three groups, namely: control, 30 min and 60 min of the
      heart stimulation at the rate of 600 times/min. The expressions of ATGL, CGI-58,
      G0S2 and HSL were evaluated at both gene and protein levels using real-time PCR
      and Western Blot analysis, respectively. Both 30 and 60 min stimulation reduced
      ATGL, HSL, CGI-58 and G0S2 mRNA content in the left ventricle. The stimulation
      had only insignificant impact on ATGL, HSL and CGI-58 transcript levels in the
      right ventricle. Interestingly, Western Blot analysis showed that the
      stimulation, regardless of the time, reduced the ATGL and G0S2 protein
      expression, but did not change the CGI-58 and HSL expression in the left
      ventricle. Furthermore, in the right ventricle, the protein expressions of ATGL,
      HSL and G0S2 decreased after stimulation. In conclusion, the obtained results
      clearly show that tachycardia affects both mRNA and protein expression of
      particular compounds of the TG lipolytic system in the heart ventricles.
      Additionally, there are marked differences in the expressions of the examined
      compounds between the ventricles.

PMID- 29375049
TI  - Vasomotor effects of hydrogen sulfide in human umbilical vessels.
AB  - Hydrogen sulfide (H2S) has recently emerged as a biologically active gas with
      multiple effects on the cardiovascular system. We aimed to investigate the
      vasomotor actions of sodium sulfide (Na2S), which forms H2S and HS- in solution,
      in human umbilical artery (HUA) and vein (HUV) rings. In addition, we examined by
      immunocytochemistry the expression and localization of cystathionine beta
      synthase (CBS), cystathionine lyase (CSE), and 3-mercaptopyruvate
      sulphurtransferase (MPST), the enzymes responsible for endogenous H2S production.
      Human umbilical vessels were compared with chicken embryo umbilical vessels. HUA
      and HUV expressed a robust signal for CSE, CBS, and 3-MPST in both endothelial
      and smooth muscle cells. However, HUA rings did not respond to Na2S (10-6M-10-3M)
      either at resting tone or during contraction evoked by serotonin or KCl.
      Similarly, the extraembryonic part of chicken allantoic artery did not respond to
      Na2S. In contrast, Na2S induced a concentration-dependent contraction in HUV
      rings under resting tone and a concentration-dependent relaxation when the H2UV
      rings were contracted with serotonin (42 +/- 5% relaxation) or KCl (12 +/- 5%
      relaxation). Na2S-induced contraction of HUV was impaired following removal of
      extracellular Ca2+, endothelial denudation, NO synthase inhibition (L-NAME), or
      soluble guanylate cyclase (sGC) inhibition (ODQ). Na2S-induced relaxation of HUV
      was impaired by the KATP channel inhibitor glibenclamide. In conclusion, H2S does
      not have vasomotor effects on HUA but induced contraction (mediated through
      inactivation of the NO/sGC axis) and relaxation (mediated through KATP channels)
      in HUV. Our data suggest a role for H2S in the venous side of human umbilical
      circulation.

PMID- 29375050
TI  - The effect of hydrogen sulfide-releasing naproxen (ATB-346) versus naproxen on
      formation of stress-induced gastric lesions, the regulation of systemic
      inflammation, hypoxia and alterations in gastric microcirculation.
AB  - Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin
      or naproxen is limited due to the gastrotoxicity evoked by these compounds.
      Endogenous hydrogen sulfide (H2s) and delivered via an H2s donor have been shown
      to play important role in the maintenance of gastric mucosal integrity. This
      study aimed to compare the effects of naproxen and an H2s-releasing naproxen
      derivative (ATB-346) on gastric lesion induction by water immersion and restraint
      stress (WRS), the alterations in gastric blood flow (GBF) and the influence of
      these drugs on systemic inflammation. Wistar rats were pretreated i.g. with
      vehicle, naproxen (20 mg/kg) or ATB-346 (equimolar dose) or NaHS (5 mg/kg), the
      H2s donor, combined with naproxen and exposed to 3.5 hours of WRS. The gastric
      lesion number and GBF were assessed by planimetry and laser Doppler flowmetry,
      respectively. Plasma concentrations of interleukins: IL-1alpha, IL-1beta, IL-2,
      IL-4, IL-5, IL-6, IL-10, IL-12, interferon-gamma (IFN-gamma), tumor necrosis
      factor-alpha (TNF-alpha) and GM-CSF were determined by Luminex system and gastric
      mucosal protein expression of cystathionine-gamma-lyase (CSE), cystathionine-beta
      synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST), nuclear factor
      (erythroid-derived 2)-like 2 (Nrf-2), hypoxia inducible factor-1alpha (HIF
      1alpha), heme oxygenase-1 (HO-1) and cyclooxygenase (COX-2) were analyzed by
      Western blot. Pretreatment with naproxen increased the number of WRS stress
      induced gastric lesions and significantly decreased GBF as compared with vehicle
      (p < 0.05). In contrast, pretreatment with ATB-346 or naproxen combined with NaHS
      significantly reduced WRS-lesions number and elevated GBF as compared with
      naproxen (p < 0.05). Naproxen significantly increased gastric mucosal protein
      expression of CSE, Nrf-2 and HIF-1alpha as compared with vehicle (p < 0.05), but
      failed to affect CBS, 3-MST and HO-1. ATB-346 significantly increased Nrf-2 and
      HO-1 protein expression as compared with vehicle (P < 0.05) but did not affect
      the protein expression of CSE, CBS, 3-MST or HIF-1alpha. ATB-346 but not naproxen
      decreased COX-2 protein expression in gastric mucosa compromised by WRS (p <
      0.05). Exposure to WRS increased plasma concentration of all investigated
      cytokines (p < 0.05). ATB-346 but not naproxen decreased plasma content of IL
      1alpha, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-alpha and IFN-gamma in rats exposed
      to WRS (p < 0.05). We conclude that H2s through its vasoactive properties
      attenuates the gastrotoxic effects of naproxen, which increased stress-induced
      hypoxia in gastric mucosa. In contrast to naproxen, ATB-346 decreased stress
      induced systemic inflammation and pro-inflammatory COX-2 expression in the
      gastric mucosa. The decreased gastrotoxicity of ATB-346 could be due to
      upregulation of Nrf-2/HO-1 pathway mediated by the release of H2s.

PMID- 29375051
TI  - Bone mineral density and the 570A>T polymorphism of the bone morphogenetic
      protein 2 (BMP2) gene in patients with inflammatory bowel disease: a cross
      sectional study.
AB  - Finding genetic predictors of osteoporosis and fractures in patients with
      inflammatory bowel disease (IBD) may provide incentives for non-pharmacological
      actions and so improve the long-term prognosis of the patients. We analysed the
      incidence of BMP2 570A>T polymorphic variants and their association with bone
      mineral density (BMD) and the incidence of fractures in patients with IBD. The
      study comprised 198 IBD patients (100 with Crohn's disease (CD), and 98 with
      ulcerative colitis, (UC)) and 41 healthy controls. Bone densitometric analysis
      was carried out using the DXA method. The 570A>T polymorphisms in the BMP2 gene
      were genotyped using RFLP. We found significant differences in the BMD and T
      scores of the lumbar spine (L2-L4) and femoral neck between the three groups. In
      controls and CD patients, the highest L2-L4 BMD was found in carriers of the AA
      variant of the BMP2 gene, while among UC patients it was the case of TT carriers.
      In both femoral neck and lumbar spine among UC patients, the highest BMD was
      observed in carriers of the TT variant of the BMP2 gene. Among patients with CD
      and in the control group, the highest L2-L4 BMD was found in carriers of the AA
      variant, whereas in UC patients, it was the case of TT homozygotes. Within the
      femoral neck, there were no significant differences in BMD for the carriers of
      individual variants of BMP2 gene polymorphism. We conclude that the 570A>T
      polymorphism of the BMP2 gene, no statistically significant relationship was
      observed between the polymorphic variant and bone mineral density or the
      incidence of fractures in IBD patients.

PMID- 29375052
TI  - Anti-inflammatory effects of nesfatin-1 on acetic acid-induced gastric ulcer in
      rats: involvement of cyclo-oxygenase pathway.
AB  - In order to elucidate the contribution of cycloxygenase (COX) enzymes in the anti
      oxidant and anti-inflammatory mechanisms of nesfatin-1, which improves the
      healing process of chronic gastric ulcers, either acetic acid (80%; ulcer groups;
      n = 40) or saline (control groups; n = 40) was applied to the serosal surface of
      male Sprague Dawley rats' stomachs for 1 min. Both the control and ulcer groups
      were treated daily with either i.p. saline or nesfatin-1 (0.3 MUg/kg; for 3
      days). Nesfatin-1-treatment was preceded with i.p. saline, COX-2 inhibitor NS-398
      (2 mg/kg), COX-1 inhibitor ketorolac (3 mg/kg) or non-selective COX inhibitor
      indomethacin (5 mg/kg) for 3 days. The rats were decapitated at the end of the
      third day, and their trunk blood was collected for the measurements of tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and IL-10 using
      ELISA. The induction of ulcers resulted in increased macroscopic scores, along
      with elevated gastric malondialdehyde, luminol- and lucigenin-enhanced
      chemiluminescence levels and myeloperoxidase activity. On the other hand,
      nesfatin-1 treatment abolished these elevations. Depleted glutathione, superoxide
      dismutase and catalase activity levels in the saline-treated ulcer group were
      preserved in the nesfatin-1-treated ulcer group. Increased levels of serum TNF
      alpha, IL-1beta, IL-10 in the saline-treated ulcer group, as compared to control
      group, were significantly decreased in the nesfatin-1-treated ulcer group. The
      inhibition of COX-1, and/or COX-2 reversed most of the alterations induced with
      nesfatin-1, but COX-2-blockade was consistently more effective to abolish all
      nesfatin-1-induced changes. Our results suggest that nesfatin-1 ameliorates ulcer
      induced inflammatory response through the modulation of oxidant-antioxidant
      balance. As selective pharmacological inhibition of COX-1 or COX-2 suppresses the
      antioxidant/anti-inflammatory effects of nesfatin-1, it appears that nesfatin-1
      decreases inflammatory mediators and neutrophil migration by a COX-dependent
      mechanism, especially by a COX-2- dependent mechanism, during the ulcer healing
      stage.

PMID- 29375053
TI  - Expression of purinergic P2X7 receptors in subpopulations of peripheral blood
      mononuclear cells in early-stage of chronic kidney disease.
AB  - Chronic kidney disease (CKD) is known as a state of chronic low-grade
      inflammation, enhancing cardiovascular risk and immunodeficiency. Purinergic
      signaling has been accepted as a crucial component in the pathogenesis of various
      diseases, mediating a vast array of biological processes. The P2X7 receptor is
      one of the important cell surface regulators of several key inflammatory
      molecules. The aim of the study was to examine the expression of surface P2X7
      receptors in subpopulations of peripheral blood mononuclear cells (PBMCs), and to
      evaluate the promising prognostic markers of inflammation (neutrophil/lymphocyte,
      Ne/Ly ratio) and cardiovascular risk (monocyte/high density lipoprotein
      cholesterol, Mo/HDL ratio) in early-stage CKD. The study involved 15 healthy
      volunteers and 15 non-diabetic patients with CKD stage 2 - 3. PBMCs were isolated
      from heparinized blood by Ficoll gradient centrifugation. To determine the
      expression of P2X7 receptors in different subpopulations (CD14+ monocytes, CD3+ T
      lymphocytes and CD19+ B-lymphocytes), the cells were stained with FITC-conjugated
      anti-P2X7. The monocyte, lymphocyte and neutrophil counts were measured in whole
      blood as a part of routine hemogram. The number of T- and B-lymphocytes was
      determined by flow cytometry using antibodies anti-CD3-PE and anti-CD19-PE,
      respectively. The expression of surface P2X7 receptors was 1.4 fold increased in
      PBMCs of CKD patients compared to healthy volunteers. The expression of P2X7
      receptors was 2.1 fold higher in monocytes and 1.5 fold higher in the whole
      lymphocyte population, with significant increase only in B-cells. The monocyte
      count, as well as the Ne/Ly and Mo/HDL ratios were also significantly increased.
      In conclusion, the increased P2X7 receptors expression in monocytes, the monocyte
      count and the Ne/Ly ratio are manifestations of chronic inflammation already in
      early stages of CKD. The study also supports recent findings that the Mo/HDL
      ratio could be used as additional parameter for monitoring cardiovascular risk
      profile in these patients.

PMID- 29375055
TI  - Polarized Emission from CsPbBr3 Nanowires Embedded-Electrospun PU fibers.
AB  - The interest in all-inorganic halide perovskites has been increasing dramatically
      due to their high quantum yield, band gap tunability, and ease of fabrication in
      compositional and geometric diversity. In this study, we synthesized um long and
      ~4 nm thick CsPbBr3 nanowires (NWs). They were, then, integrated into electrospun
      polyurethane (PU) fibers to examine polarization behavior of the composite fiber
      assembly. Aligned electrospun fibers containing CsPbBr3 nanowires show remarkable
      increase in degree of polarization from 0.17 to 0.30. This combination of NWs and
      PU fibers provides a promising composite material for various applications such
      as optoelectronic devices and solar cells.

PMID- 29375054
TI  - Magnetic nanocomposites based on phosphorus-containing polymers-structural
      characterization and thermal analysis.
AB  - Fabrication of magnetic nanocomposites containing iron oxide nanoparticles formed
      in situ within a phosphorus-containing polymer matrix as well as its structural
      characterization and its thermal degradation is reported here. Comparative
      structural studies of the parent polymer and nanocomposites were performed using
      FTIR spectroscopy, x-ray diffraction, and atomic force microscopy. The results
      confirmed the presence of dispersed iron oxide magnetic nanoparticles in the
      polymer matrix. The formed composite combines the properties of porous polymer
      carriers and magnetic particles enabling easy separation and reapplication of
      such polymeric carriers used in, for example, catalysis or environmental
      remediation. Studies on thermal degradation of the composites revealed that the
      process proceeds in three stages while a significant influence of the embedded
      magnetic particles on that process was observed in the first two stages. Magnetic
      force microscopy studies revealed that nanocomposites and its calcinated form
      have strong magnetic properties. The obtained results provide a comprehensive
      characterization of magnetic nanocomposites and the products of their calcination
      that are important for their possible applications as sorbents (regeneration
      conditions, processing temperature, disposal, etc).

PMID- 29375056
TI  - Introduction to the Special Issue.

PMID- 29375057
TI  - The Abuse of Futility.
AB  - Two recent policy statements by major providers of critical care have rejected
      the concept and language of "medical futility," on the ground that there is no
      universal consensus on a definition. They recommend using "potentially
      inappropriate" or "inappropriate" instead. We argue that their proposed terms are
      vague-even misleading-in the ICU setting, where serious life-and-death decisions
      are made. Whatever specific meaning the exclusive world of critical care might
      wish to give to the word inappropriate, in the lay world the term is so broad it
      trivializes the activity. We also point out that there is no universal consensus
      on the definition of death, the right to abortion, or the right to refuse blood
      products, yet medicine carries on. One advantage of the term "medical futility"
      is that it confirms unambiguously that human beings are mortal, and medicine's
      powers are limited. It leads more naturally to integrating palliative and comfort
      care into critical care decision-making and encourages health providers to think
      more deeply about their role in the inevitable ending of their patients' lives.

PMID- 29375058
TI  - Resolving Family-Clinician Disputes in the Context of Contested Definitions of
      Futility.
AB  - The word futile has been a touchstone in debates regarding resolution of disputes
      regarding life-prolonging treatments since the 1980s. Here, we respond to several
      criticisms of the Multiorganization Policy Statement, "An Official
      ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially
      Inappropriate Treatments in Intensive Care Units" (Bosslet et al. 2015). This
      response highlights the need for a strict definition of the word futile in order
      to avoid undue treatment differences when end-of-life interventions are
      contested. We also reply to several criticisms of this policy statement that are
      formulated upon fundamental misunderstandings of the statement and its
      assertions.

PMID- 29375059
TI  - Getting Past Words: Futility and the Professional Ethics of Life-Sustaining
      Treatment.
AB  - For nearly three decades, clinicians and bioethicists have debated about use of
      the term futile to describe end-of-life medical interventions that clinicians
      believe are no longer warranted. In clinical practice, the term is most often
      invoked when a family of a dying or permanently unconscious patient insists upon
      such interventions, despite the medical team's belief or recommendation that they
      be withheld or withdrawn. This essay argues that each of the commonly used terms
      for these interventions (futile, inappropriate, and nonbeneficial) captures an
      important, different, and complementary facet of these conflicts in end-of-life
      medical care. Rather than continuing to debate which term is best, clinicians and
      bioethicists should direct their attention to the professional ethics of end-of
      life care and the clinical and organizational factors that create or contribute
      to these so-called "futility cases."

PMID- 29375060
TI  - Futility: Definition and Goals.
AB  - Schneiderman, Jecker, and Jonsen (2017) correctly take issue with a recent multi
      society statement that attempts to replace most uses of the term futility with
      "inappropriate treatment." However, they mistakenly categorize any treatment of
      permanent unconsciousness as futile. Futility can be readily defined as an
      intervention that will not work, and it is always an incomplete statement unless
      one specifies the goal one hopes to achieve.

PMID- 29375061
TI  - Futile Treatment and Conquering Death.
AB  - Pragmatically speaking, there is a stronger case for using the language of
      "futility" than "potentially appropriate" for end-of-life care. The latter
      obscures the reality of death as a part of human life. Do patients die because
      death always wins in the end? Or do they die because physicians run out of ways
      to treat them? In the end, modern medicine has made the conquest of death its de
      facto goal. That is a fundamental error, one which the language of "potentially
      appropriate" is unwittingly supportive of.

PMID- 29375062
TI  - Who Will Teach Us to Die?: Reflections on Futility and Finitude.
AB  - Futility is a medical judgment, but more importantly it is a prognostic gesture
      for shaping relationships among doctors, patients, and their families. As such,
      the need for a concept of futility, or something like it, is personally and
      socially important to all of us. It is one of medicine's essential tools for
      teaching about finitude and mortality.

PMID- 29375063
TI  - The Brutal but Utile Truth of "Futile".
AB  - Though futility may be difficult to consensually define as a description of the
      limits of medicine, the term futility as it applies to quantitative futility is
      useful and apt. The term conveys a sometimes harsh but truthful reality for
      patients and families. When talking with patients and families, conveying the
      concept of futility might be more compassionately expressed as an inability to
      provide a curative medical benefit to the patient, with a concomitant commitment
      to provide comfort care. The ultimate arbiter of quantitative futility should be
      the medical profession.

PMID- 29375064
TI  - Futility, Inappropriateness, Conflict, and the Complexity of Medical Decision
      Making.
AB  - The concepts of medical futility and "potentially inappropriate" interventions
      aim to describe particular decision-making situations and assist in making
      ethically sound decisions. This article explores how both of these concepts
      simplify the rather more complicated decision-making task in ways that often
      hinder their ability to be helpful, and potentially allow for unstated biases to
      influence decisions. Instead of searching for a single unifying phrase or
      concept, acknowledging and explicitly working with the numerous judgments and
      decisions that comprise a high-stakes medical treatment decision will do more to
      advance ethically sound decision-making.

PMID- 29375065
TI  - Futility, the Multiorganization Policy Statement, and the Schneiderman Response.
AB  - This essay offers a brief history of futility, in both sociocultural and medical
      contexts, with some personal reflection on the disappearance and reappearance of
      medical futility during the author's 40-plus years in medicine. It discusses the
      creation of the Texas Advance Directives Act (TADA), which, even with its flaws,
      creates the only legal safe harbor for physicians engaged in futility disputes.
      It also offers reflection on the commendable Multiorganization Policy Statement
      on "potentially inappropriate treatment" yet comes to the same conclusion as
      Schneiderman. The words recommended for use in futility disputes are not helpful
      in facing these disputes. Medical futility appropriately understood transcends
      pure physiologic, quantitative, or qualitative concepts. Those who seek to help
      resolve futility disputes must take into account not only these concepts, but
      also emotional, social, and spiritual factors as well. If we are to collectively
      face the challenge of medical futility, we must cultivate a more covenantal and
      communitarian ethical framework, develop processes similar to TADA in other state
      laws, and teach that the acceptance of finitude does not reduce the sacred value
      of life.

PMID- 29375066
TI  - "Futility" as in English or "Futilities" as in French: A Valuable Semantic
      Misunderstanding?
AB  - This article offers a comparative perspective of the controversy about the use of
      the term futility as presented by Schneiderman and colleagues (2017). The English
      concept of "medical futility" has no semantic equivalent in the French language.
      The traditional term used to translate it was "therapeutic obstinacy," which
      changed to "unreasonable obstinacy" when the first end-of-life law was adopted in
      2005. The change was done in order to demedicalize the concept and make it less
      objective and less scientific. As such, the intention of the French legislature
      may have been equivalent to the intention behind the recent U.S. policy statement
      that proposed replacing the term futile with inappropriate (Bosslet et al. 2015).
      The semantic change towards "unreasonable obstinacy" pushed practitioners in
      France to the same conclusion formalized some years ago by Helft and colleagues
      (2000), who said that pronouncing the term futility can't be enough by itself to
      convince patients or their proxies that the treatments should be ceased. Instead,
      it should initiate the difficult task of negotiating until they will accept that
      there is no other issue for the patient but the withdrawal of all aggressive and
      invasive treatments. The best way to enter this cruel negotiation remains
      unresolved. Is it in using the term futility, which involves a notion of medical
      undisputable objectivity, as well as an ending dimension that is difficult for
      people to be confronted with? Or is it in choosing a less definitive word, which
      leaves room for something else to happen and to be positively constructed, in
      order to escape the dimension of hopelessness included in the announcement of
      futility?

PMID- 29375067
TI  - Mediative Fluency and Futility Disputes.
AB  - Futility disputes are more likely to be resolved-and relational breaches repaired
      by engaging in a process that fosters communication between clinicians, patients,
      and families. This essay calls for mediative fluency. The preemptive use of a
      futility definition can stifle conversation when it is needed most, exacerbating
      the very power imbalances and associated health disparities that often
      precipitate futility disputes. When clinicians, patients, and families engage in
      dialogue, clinicians can appreciate what motivates requests for what is thought
      to be futile care, and patients and families can better understand the limits of
      available therapies. This sharing of knowledge, values, and attitudes cannot be
      achieved through the unilateral invocation of a futility definition. Furthermore,
      futility definitions are prone to interpretative judgment by clinicians and can
      be informed by the norms and attitudes attendant to a practitioner's medical
      specialty. They also need to be interpreted in the context of emerging trends in
      medical therapeutics and in relation to the clinical details of each case. In the
      aggregate, these challenges make the application of a futility definition futile.

PMID- 29375068
TI  - Futile and Potentially Inappropriate Interventions: Semantics Matter.
AB  - In 1997, the Society for Critical Care Medicine (SCCM) published a statement
      regarding futile and inadvisable treatments. Recently, five critical care
      organizations published a consensus statement supporting and expanding upon the
      1997 SCCM statement, and the SCCM issued a companion statement defining futile
      and potentially inappropriate interventions. In all of these statements, there is
      agreement that the term futile should be used only when an intervention cannot
      accomplish the intended physiologic goal. The organizations provide
      recommendations for optimizing communication, however even when clinicians use
      excellent communication techniques, there are times when competing ethical
      considerations mean that a surrogate persists in requesting an intervention that
      the clinician does not believe is justified. In such cases, clinicians should not
      label the requested intervention as futile, because doing so is disrespectful to
      patients and families, overly empowers clinicians, and stifles communication.
      When clinicians believe that they are justified in declining such a request due
      to differences in values or beliefs, they should refer to the requested treatment
      as "potentially inappropriate," indicating that the disagreement is based on
      values, and that any decision to withhold the requested intervention is
      preliminary until reviewed through a fair process.

PMID- 29375069
TI  - Intractable Disagreements About Futility.
AB  - This paper discusses the inevitable ambiguity of the language that we use to
      describe events that are rare and emotionally devastating. A search for precision
      in such circumstances may distract from more important issues. Neither families
      nor doctors need more precise language. Instead, they need more trust, more
      emotional transparency, and a recognition by doctors of the tragic nature of the
      decision they face.

PMID- 29375070
TI  - Medical Futility and "Brain Death".
AB  - Judgments of futility are always relative to some goal. In light of that
      proposition, continued treatment for those diagnosed as "brain dead" is not
      necessarily futile.

PMID- 29375071
TI  - The True Abuse of Futility.
AB  - Futility has wrongly been applied over the past decades to clinical scenarios
      where treatment disputes exist, but where true physiological futility is not
      certain. This particularly applies to the pediatric critical care arena, where a
      major source of ethical debate and moral concern surrounds decisions about
      appropriateness of treatment, and not necessarily futility. In the pediatric
      intensive care unit, Schneiderman and colleagues' (2017) definitions of
      quantitative and qualitative futility are rarely applicable. Attempted
      alterations to the definition of futility have failed to encapsulate the complex
      and complicated clinical scenarios encountered, as well as the difficulty of
      balancing the provision of best medical advice with parental values and
      authority. The Multiorganization Policy Statement recognizes the difference
      between futile and potentially inappropriate treatments and puts forth
      communication strategies to reconcile disputes about the latter. This approach is
      of value to the greater medical community, including pediatric critical care, and
      also restores an important and specific meaning to the term futile-a word whose
      meaning should be unambiguously clear.

PMID- 29375072
TI  - Criterialism versus Deliberativism.
AB  - The argument in this paper is that the position of Schneiderman, Jecker, and
      Jonsen (2017) suffers from the very flaws of which they accuse the
      Multiorganization Policy Statement, and that all the ethical and conceptual
      arguments speak in favor of the collaborative, deliberativist position that
      underlies the Multiorganization Statement. That position is that we should
      abandon self-sealing definitions of futility, which disguise the value judgments
      inherent in them, in favor of the evolving, collaborative process of decision
      making.

PMID- 29375073
TI  - Medical Futility and Involuntary Passive Euthanasia.
AB  - Conflicts between providers and patients or their families surrounding end-of
      life care are both regrettable and extremely challenging, interpersonally and
      ethically, for all involved. These conflicts often implicate the concept of
      medical futility. The concept of futility is too often conflated with distinct
      concepts that are more ethically salient, including the fiduciary responsibility
      to assess surrogate decision-making, and distributive justice. By distinguishing
      these concepts from futility, it becomes clear that there are some situations in
      which forgoing life-sustaining treatment over objection is permissible, and
      perhaps even obligatory. But the justification lies in the constellation of
      rights and responsibilities surrounding surrogate decision-making, or in
      distributive justice, but not futility. Once futility is disambiguated from these
      other concepts, the practice of withholding or withdrawing life-sustaining
      treatment over the objection of a valid surrogate or a competent patient, based
      on the alleged futility of such treatment, is more clearly described as
      involuntary passive euthanasia.

PMID- 29375074
TI  - Medical Futility and Potentially Inappropriate Treatment: Better Ethics with More
      Precise Definitions and Language.
AB  - The primary objective of this article is to defend the vocabulary in the
      Multiorganization Policy Statement. The Multiorganization Statement narrows but
      does not abolish the term futility. Rather, it offers a richer and more precise
      vocabulary that facilitates better ethical decision-making. The secondary
      objective of this article is to defend the continuing utility of the terms and
      concepts "quantitative futility" and "qualitative futility" defended by
      Schneiderman, Jecker, and Jonsen (2017).

PMID- 29375075
TI  - The Concept of Futility: Recognizing the Importance of Context.
AB  - Debate about the concept of medical futility is often polarized around two views.
      One is that futility is simply an acknowledgment of the limitations of modern
      medicine, a corollary of the fact of human mortality. The other is that futility
      is a judgment that is always grounded in a particular set of values, and that
      medical professionals have no right to impose their value judgments on patients
      and families who do not share their perspective. This essay argues that these
      dichotomous views can be reconciled by appreciating the importance of the context
      in which the dialogue occurs. When clinicians and families are working
      collaboratively in a process of shared decision-making, use of the concept of
      futility in the former sense can be an effective way of capturing the limits of
      medicine. When communication and trust have broken down and the parties are
      engaged in a process of conflict resolution, the latter interpretation of
      futility is necessary in order to demonstrate respect for those who embrace a
      different set of values and perspectives.

PMID- 29375076
TI  - End-of-Life Futility Conversations: When Language Matters.
AB  - Futility is a term that is distressing for many, but it is a concept that merits
      revisiting for its normative, empirical, and ethical value in understanding end
      of-life issues. Ethical concerns surrounding aggressive care and the suffering of
      patients at end of life are frequently cited as significant ethical issues within
      institutional settings, leading to clinicians' moral distress. The author
      responds to the essay on "The Abuse of Futility" by Schneiderman, Jecker, and
      Jonsen (2017), who support the continual use of futility language with patients
      and families. Others, however, suggest a reexamination of its usage. Concepts are
      not static, but the reconceptualization of futility language requires further
      clarification and analysis of how newer terms impact the patients and families
      who rely on their clinicians for expert care and compassion at end of life.

PMID- 29375077
TI  - Why Some "Futile" Care Is "Appropriate": The Implications for Conscientious
      Objection to Contraceptive Services.
AB  - In response to the criticism of Schneiderman and colleagues (2017) that two
      recent policy statements of professional medical organizations referred to some
      medical treatment that were traditionally called "futile" by the terms
      "inappropriate" or "potentially inappropriate," this critique accepts their claim
      challenging these terms as being hopelessly ambiguous. However, this critique
      rejects the conclusion they all share that clinicians or hospitals should have
      the unilateral authority to refuse to provide treatments that will plausibly
      achieve the end that the patient or surrogate is pursuing. Although clinicians
      should be presumed authoritative in deciding to reject treatments that will not
      achieve the patient or surrogate's end, they should be obligated, provided five
      conditions are met, to provide those treatments that will achieve the patient or
      surrogate's end. The implications of honoring a physician's right to
      conscientious objection to treatments they deem "futile" are compared to
      physician claims of the right to refuse to provide contraceptive services on the
      same grounds.

PMID- 29375078
TI  - Nurturing Futility in the NICU: The Dutch Perspective.
AB  - Requests for life-prolonging treatments can cause irresolvable conflicts between
      health-care providers and surrogates. The Multiorganization Policy Statement
      (Bosslet et al. 2015) with recommendations to prevent and manage these conflicts
      creates a good opportunity to examine how end-of-life decisions are made in Dutch
      neonatal intensive care units and how medical futility is defined. The Dutch
      equivalent of medical futility in the context of NICU care has grown and
      developed rather independently, within the typical legal, ethical, and cultural
      framework of Dutch society. Moreover, intractable conflicts and legal claims
      about life-prolonging treatments of newborns are very rare. This makes the
      Multiorganization Statement recommendations only partly relevant to Dutch
      practice. Critics are right in their comments that a substitution for the term
      futility, as recommended in the statement, is unlikely to prevent or solve
      irresolvable conflicts. But the recommended transparency about limit setting may
      work well, provided physicians make sure that comfort and palliative care are
      always provided.

PMID- 29375079
TI  - Morphological analyses of the retinal photoreceptor cells in the nocturnally
      adapted owl monkeys.
AB  - Owl monkeys are the only one species possessing the nocturnal lifestyles among
      the simian monkeys. Their eyes and retinas have been interested associating with
      the nocturnal adaptation. We examined the cellular specificity and
      electroretinogram (ERG) reactivity in the retina of the owl monkeys by comparison
      with the squirrel monkeys, taxonomically close-species and expressing diurnal
      behavior. Owl monkeys did not have clear structure of the foveal pit by the
      funduscope, whereas the retinal wholemount specimens indicated a small-condensed
      spot of the ganglion cells. There were abundant numbers of the rod photoreceptor
      cells in owl monkeys than those of the squirrel monkeys. However, the owl
      monkeys' retina did not possess superiority for rod cell-reactivity in the
      scotopic ERG responses. Scanning electron microscopic observation revealed that
      the rod cells in owl monkeys' retina had very small-sized inner and outer
      segments as compared with squirrel monkeys. Owl monkeys showed typical nocturnal
      traits such as rod-cell dominance. However, the individual photoreceptor cells
      seemed to be functionally weak for visual capacity, caused from the morphological
      immaturity at the inner and outer segments.

PMID- 29375080
TI  - JTE-852, a novel spleen tyrosine kinase inhibitor, blocks antigen-induced
      allergic reactions in rats.
AB  - Conventional clinical treatments for allergy management remain suboptimal; new,
      orally available medications that improve a wide range of allergic signs have
      been desired. We previously demonstrated that JTE-852, a novel spleen tyrosine
      kinase inhibitor, potently and simultaneously suppresses secretion of granule
      contents, arachidonate metabolites, and cytokines from mast cells stimulated by
      immunoglobulin E-crosslinking. In the present study, we investigated the effects
      of JTE-852 in four rat models (sneezing, rhinorrhea, airway constriction, and
      airway inflammation) as representatives of allergy models. Rats were sensitized
      and challenged with antigen. Allergic reactions developed after challenge were
      detected. JTE-852 and current anti-allergic drugs (ketotifen, pranlukast, and
      prednisolone) were administered orally before challenge. JTE-852 showed
      significant blocking effects on antigen-induced allergic reactions in all models,
      indicating that JTE-852 in oral dosage form would improve a wide range of
      allergic signs. The current anti-allergic drugs, on the other hand, failed to
      display significant suppression in several models. Because JTE-852 suppresses the
      secretion of all three groups of allergic mediators from mast cells, it would be
      capable of targeting signs that current drugs cannot sufficiently relieve. We
      anticipate JTE-852 to be a promising new anti-allergic drug that is potentially
      more effective than conventional drugs.

PMID- 29375081
TI  - Late-night-dinner is associated with poor glycemic control in people with type 2
      diabetes: The KAMOGAWA-DM cohort study.
AB  - Skipping breakfast or irregular breakfast is associated with poor glycemic
      control. However, a relationship between the timing of dinner and glycemic
      control in people with type 2 diabetes remains indefinite. Therefore, we
      investigated the relationship between late-night-dinner and glycemic control in
      people with type 2 diabetes. We performed questionnaire survey for lifestyle
      factors in this cross-sectional study. We defined having dinner later than eight
      pm as late-night-dinner. We examined the differences in clinical and metabolic
      parameters between those who have late-night-dinner and those who do not have. We
      also examined the relationship between late-night-dinner and HbA1c, using
      multiple regression analysis. Ninety-five people (23.2%) had a late-night-dinner,
      among 409 people with type 2 diabetes. Metabolic parameters (mean (SD) or median
      (interquartile range)) of people with late-night-dinner were worse than those of
      without, including body mass index (BMI) (24.4 (4.0) vs. 23.2 (3.4) kg/m2, p =
      0.006), triglycerides (1.5 (1.1-2.1) vs. 1.2 (0.8-1.7) mmol/L, p < 0.001), HDL
      cholesterol (1.4 (0.4) vs. 1.6 (0.4) mmol/L, p = 0.004) and hemoglobin A1c (58.1
      (13.3) vs. 55.2 (10.2) mmol/mol, (7.5 (1.2) vs. 7.2 (0.9) %), p = 0.023)). Late
      night-dinner (standardized regression coefficient = 0.13, p = 0.028) was
      associated with hemoglobin A1c after adjusting for age, BMI, sex, duration of
      diabetes, smoking, exercise, alcohol, snacking after dinner, nighttime sleep
      duration, time from dinner to bedtime, skipping breakfast, and medication for
      diabetes. Late-night-dinner is independently associated with poor glycemic
      control in people with type 2 diabetes.

PMID- 29375082
TI  - Efficacy and safety of sodium-glucose cotransporter 2 inhibitors as add-on to
      metformin and sulfonylurea treatment for the management of type 2 diabetes: a
      meta-analysis.
AB  - This study evaluates the efficacy and safety of sodium-glucose cotransporter 2
      (SGLT2) inhibitors as add-on to metformin and sulfonylurea treatment for type 2
      diabetes management. The literature search was conducted in electronic databases
      and meta-analyses of mean differences in the changes from baseline in selected
      disease endpoints (efficacy endpoints) or odds ratios (for safety endpoints) were
      performed to compare outcomes between SGLT2 inhibitor- and placebo-/comparator
      treatments. Seven studies (5,143 patients; age 56.75 years [95% CI: 56.19,
      57.37]; body mass index 29.53 kg/m2 [28.23, 30.83]; and 51.87% [50.46, 53.57]
      males) were included. Compared to placebo, SGLT2 inhibitors significantly (p <
      0.00001) reduced glycated hemoglobin (HbA1c; -0.79% [95% CI: -0.90, -0.68]),
      fasting plasma glucose (FPG; -1.73 mmol/L [-1.86, -1.60]) and body weight (-1.85
      kg [-2.11, -1.59]) after 52-78 weeks of treatment. There were no significant
      differences in reduction of either HbA1c, FPG or body weight between 18-24 weeks
      and after 52-76 weeks of treatment. Treatment with SGLT2 inhibitors as add-on to
      metformin and sulfonylurea was also associated with significant reductions in
      blood pressure and triglycerides and increase in high-density lipoprotein
      cholesterol. Incidence of hypoglycemia was significantly higher, but incidence of
      hyperglycemia was significantly lower in SGLT2 inhibitor group. Overall, drug
      related adverse events were more common in SGLT2 group mainly due to higher
      incidence of genital tract infections.

PMID- 29375084
TI  - What does Commercial Database Tell us About Medical Sciences?

PMID- 29375085
TI  - The roles of kisspeptin and gonadotropin inhibitory hormone in stress-induced
      reproductive disorders.
AB  - Several kinds of stress suppress the hypothalamic-pituitary-gonadal (HPG) axis
      and reproductive behavior in humans and animals. These changes can eventually
      cause diseases and disorders, such as amenorrhea and infertility. In previous
      studies, it has been shown that stress-related factors, e.g., corticotropin
      releasing hormone, cortisol, and pro-inflammatory cytokines, promote the stress
      induced suppression of the HPG axis. However, these mechanisms are not sufficient
      to explain how stress suppresses HPG axis activity, and it has been suggested
      that some other factors might also be involved. In the early 21st century, novel
      neuroendocrine peptides, kisspeptin and gonadotropin inhibitory hormone
      (GnIH)/RFamide-related peptide 3 (RFRP-3), which directly regulate
      GnRH/gonadotropin synthesis and secretion, were newly discovered. Growing
      evidence indicates that kisspeptin and GnIH/RFRP-3 play pivotal roles in the
      stress-induced disruption of the HPG axis and reproductive behavior in addition
      to their physiological functions. This review summarizes what is currently known
      about the roles of kisspeptin and GnIH/RFRP-3 in stress-induced reproductive
      disorders.

PMID- 29375083
TI  - Additive Prognostic Value of Carotid Plaque Score to Enhance the Age, Creatinine,
      and Ejection Fraction Score in Patients with Acute Coronary Syndrome.
AB  - AIM: To assess whether combining measurements obtained from carotid
      ultrasonography in addition to the age, creatinine, and ejection fraction (ACEF)
      score would improve the predictive ability of outcome in patients with acute
      coronary syndrome (ACS). METHODS: We examined 264 patients with ACS (194 men;
      mean age: 68+/-11 years) who underwent percutaneous coronary intervention. The
      carotid plaque score (cPS) and intima-media thickness (cIMT) were determined by
      carotid ultrasonography. The modified ACEF score was calculated using the
      following formula: (age/left ventricular ejection fraction) +1 point for every 10
      mL/min reduction in creatinine clearance below 60 mL/min per 1.73 m2. The
      endpoint of this study was major adverse cardiovascular and cerebrovascular
      events (MACEs), defined as all-cause death, myocardial infarction, stoke, and
      target vessel revascularization. RESULTS: During the median 4-year follow-up,
      there were 121 incidents of MACEs. Multivariate Cox proportional hazard
      regression analysis revealed that cPS >=9.8 (hazard ratio [HR], 1.52; 95%
      confidence interval [CI], 1.01-2.31) and ACEF score >=1.20 (HR, 1.62; 95% CI,
      1.11-2.39) were significantly associated with MACEs, whereas cIMT was not. When
      the new combined risk score was calculated by multiplying the cPS by the modified
      ACEF score, the freedom from MACEs at 5 years was 71% and 31% for the lower and
      higher scores, respectively (p<0.001). The area under the receiver-operating
      characteristic curve for MACEs for the ACEF score, cPS, and combined risk score
      were 0.65, 0.66, and 0.71, respectively (p<0.05). CONCLUSION: The cPS offers an
      incremental predictive value when combined to the simple ACEF score in ACS.

PMID- 29375086
TI  - Asymptomatic Penetration of Oculomotor Nerve by Internal Carotid-Posterior
      Communicating Artery Aneurysm Presenting Pure Acute Subdural Hematoma: A Case
      Report.
AB  - To present a unique case of the internal carotid artery-posterior communicating
      artery (ICA-PcomA) aneurysm penetrating the oculomotor nerve presenting a pure
      acute subdural hematoma (ASDH) without any oculomotor dysfunction. A 71-year-old
      woman presented with a sudden headache and drowsiness. She had no history of head
      trauma and did not manifest any neurological deficits including oculomotor nerve
      palsy. Computed tomography (CT) of her head revealed left ASDH. Subsequent CT
      angiography showed an aneurysm originating from the left ICA with an inferior
      projection having continuity with the hematoma. Intraoperative inspection
      revealed ASDH observed mainly in middle fossa and no subarachnoid hemorrhage,
      while the aneurysm was confirmed to split the oculomotor nerve and to be fixed
      with the middle fossa. The aneurysm was obliterated by direct clip application
      and the patient's postoperative course was uneventful. Oculomotor nerve palsy is
      an important warning sign of imminent rupture of ICA-PcomA aneurysm. However, we
      should consider that the ICA-PcomA aneurysm could rupture causing ASDH without
      any oculomotor nerve palsy, even though the aneurysm penetrated the oculomotor
      nerve.

PMID- 29375087
TI  - Clinical outcome of canine cardiopulmonary resuscitation following the RECOVER
      clinical guidelines at a Japanese nighttime animal hospital.
AB  - A set of evidence-based consensus guidelines for cardiopulmonary resuscitation
      (CPR) in dogs and cats (RECOVER guidelines) was published in 2012. The purpose of
      this study was to investigate the clinical outcomes of CPR performed according to
      those guidelines in dogs. A total of 141 dogs with cardiopulmonary arrest (CPA)
      were identified and underwent CPR between January 2012 and December 2015 at the
      Sapporo Nighttime Animal Hospital. CPR was performed according to no-consensus
      traditional veterinary CPR procedures in 68 dogs (TRADITIONAL group), and
      according to the RECOVER guidelines in 73 dogs (RECOVER group). There was no
      significant difference in the age, body weight, or time from CPA identification
      to initiation of CPR between the TRADITIONAL and RECOVER groups (median [range]:
      10 [0-16] vs. 11 [0-16] years; 6.6 [1.0-58.6] vs. 5.5 [1.1-30.4] kg; and 0 [0-30]
      vs. 0 [0-30] min, respectively). In the TRADITIONAL group, 12 dogs (17%) achieved
      a return of spontaneous circulation (ROSC), but none survived to hospital
      discharge. However, 32 dogs (43%) in the RECOVER group achieved ROSC, and 4 dogs
      (5%) were discharged from the hospital. Incorporating the RECOVER guidelines into
      clinical practice significantly improved the ROSC rate (P<0.001). However, the
      rate of survival to hospital discharge was still low. This may suggest that a
      superior intensive care unit that provides advanced post-CPA care could benefit
      veterinary CPR patients.

PMID- 29375088
TI  - Minimizing an outbreak of avian botulism (Clostridium botulinum type C) in
      Incheon, South Korea.
AB  - An outbreak of botulism occurred over a two-month period beginning July 20, 2016.
      In all, 697 wild birds were found paralyzed or dead at the Namdong reservoir and
      11 Gong-gu. Using a mouse bioassay, type C botulinum toxin was identified in the
      bird serum, liquid cultures of soil samples, and maggot extracts. To minimize
      further infection of wild birds, we opened the floodgates of the Namdong
      reservoir adjacent to the Yellow Sea; this decreased the water temperature and
      the nutrient load such as nitrogen and phosphorus. The outbreak stopped shortly
      after taking these actions. It is not known if these efforts decreased the number
      of dead and diseased wild birds. Our study demonstrates one potential approach to
      minimize future botulism outbreaks among wild birds and their habitats.

PMID- 29375090
TI  - Influence of ultraviolet irradiation treatment on porcelain bond strength of
      titanium surfaces.
AB  - To determine the effect of titanium (Ti) surface modification by ultraviolet
      irradiation (UVI) on the bond strength between Ti and porcelain. Grade 2 Ti
      plates were allotted to five groups: sandblasted (SA), 15 min UVI (UV), SA+5 min
      UVI (SA+UV5), SA+10 min UVI (SA+UV10), and SA+15 min UVI (SA+UV15). After surface
      treatment, porcelain was added. A precious metal (MC) was used for comparison
      with Ti. The effects of 24-h storage at room temperature versus thermal cycling
      only at 5 and 55 degrees C in water were evaluated. Subsequently, the tensile
      strength of each sample was tested. Data were analyzed using one-way analysis of
      variance and the Tukey test. In both the room temperature and thermal cycling
      groups, the MC and SA+15 min UVI samples showed significantly greater bond
      strengths than the other samples (p<0.05). UVI processing efficiently increases
      the bond strength between porcelain and the Ti surface.

PMID- 29375089
TI  - Immunohistochemical localization of inhibin/activin subunits in adult Asian
      elephant (Elephas maximus) testes.
AB  - Immunolocalization of inhibin-alpha and inhibin/activin betaA and betaB subunits
      in the testes of Asian elephant was determined. Testicular sections were
      immunostained with polyclonal antisera against inhibin subunit-alpha and
      inhibin/activin betaA and betaB using the avidin-biotin-peroxidase complex
      method. Positive immunostaining against inhibin-alpha subunit was strongly
      present in Sertoli cells, and positive immunostaining for the inhibin/activin
      betaA and betaB subunits was observed in both Sertoli and Leydig cells. These
      results indicated that while Sertoli cells are the predominant source of inhibin
      and activin secretions in the testes of adult male Asian elephant, Leydig cells
      are a source of activin but not inhibin.

PMID- 29375091
TI  - Assessment of cuspal deflection and volumetric shrinkage of different bulk fill
      composites using non-contact phase microscopy and micro-computed tomography.
AB  - The understanding of cuspal deflection and volumetric shrinkage of resin
      composites is necessary to assess and improve the placement techniques of resin
      based materials. The aim of this study was to investigate the cuspal deflection
      and its relationship with volumetric polymerization shrinkage of different bulk
      fill resin composites. The investigation was conducted using non-contact phase
      microscopy and micro-computed tomography. Thirty custom-milled aluminum blocks
      were fabricated for microscopy analysis and thirty-six tooth models with
      standardized Class I cavities were used for micro-computed tomography analysis.
      Results showed that high-viscosity composites present higher cuspal deflection
      compared to bulk-fill composites. The filler loading of resin composites seems to
      have an effect on cusp deflection, since the higher the filler content
      percentage, the higher the cusp deflection. On the other hand, it seems to have
      an opposite effect on volumetric shrinkage, since higher filler loadings produced
      lower volumetric shrinkage percentages.

PMID- 29375092
TI  - Effects of different sulfuric acid etching concentrations on PEEK surface bonding
      to resin composite.
AB  - This study evaluated the effects of surface pretreatment with different
      concentrations of sulfuric acid etching on surface properties and bonding between
      Polyetheretherketone (PEEK) and a resin composite. Six groups of surface
      pretreatment (no pretreatment, etched with 70, 80, 85, 90, and 98% sulfuric acid
      for 60 s) were treated on PEEK. Surface roughness, scanning electron microscopy
      (SEM) and atomic force microscopy (AFM) analyses were examined. Shear bond
      strength (SBS) and cross-sectional observations of the interfaces were performed.
      One-way ANOVA analysis revealed differences in surface roughness and SBS between
      groups. The 90 and 98% sulfuric acid etching significantly achieved the highest
      SBS (p<0.05). SEM and AFM demonstrated etched surfaces with wide and deep pores.
      The 90 and 98% sulfuric acid etching were suggested to be the optimal
      concentration to improve adhesion between PEEK and the resin composite.

PMID- 29375093
TI  - Effect of silane compounds on bonding to fused quartz of tri-n-butylborane
      initiated resin.
AB  - This study aimed to investigate how different compositions of experimental silane
      based primers in a methyl methacrylate solution containing 3
      (trimethoxysilyl)propyl methacrylate (3-TMSPMA) or 3-(4
      methacryloyloxyphenyl)propyl trimethoxysilane (3-MPPTS) might act as silicon
      dioxide bonding agents. With or without post-silanization heat treatment, primer
      treated quartz discs were bonded using the MMA-TBB resin and their bond strengths
      were evaluated. The disks were primed with one of the following materials: 1 mol%
      3-TMSPMA, 2 mol% 3-TMSPMA, 1 mol% 3-MPPTS, and 2 mol% 3-MPPTS. Shear bond
      strength was determined both before and after thermocycling. Statistical analyses
      were performed with non-parametric procedure (Kruskal-Wallis, Mann-Whitney U, and
      Steel-Dwass tests). Both primers were effective with heat treatment to enhance
      bonding between quartz and the MMA-TBB, and the bonding durability of the 1 and 2
      mol% 3-MPPTS (16.8 and 24.9 MPa) with heat groups was significantly higher than
      in the 1 and 2 mol% 3-TMSPMA (5.4 and 9.8 MPa) with heat groups.

PMID- 29375094
TI  - Novel antibacterial mouthguard material manufactured using silver-nanoparticle
      embedded ethylene-vinyl acetate copolymer masterbatch.
AB  - The purpose of the present study was to develop an antibacterial mouthguard (MG)
      material using a masterbatch of silvernanoparticle-embedded ethylene-vinyl
      acetate (EVA) copolymers. In order to verify that the testing material was
      clinically applicable as an antibacterial MG material, we conducted an
      antibacterial test, a shock absorption test, and analysis of in vitro silver
      release. The colony-forming activity of Streptococcus sobrinus, Porphyromonas
      gingivalis, and Escherichia coli were significantly inhibited on the testing
      materials compared with the commercial EVA sheet (p<0.05). The shock absorption
      capability of the testing material was not significantly different from that of
      the commercial EVA sheet. Cumulative silver release (in pure water) from the
      testing materials were infinitesimal after soaking for 20 days, which implied
      that there could be no harm in wearing the MG during exercise. These results
      showed that this testing material could be clinically applicable as an
      antibacterial MG material.

PMID- 29375095
TI  - Ca-P spots modified zirconia by liquid precursor infiltration and the effect on
      osteoblast-like cell responses.
AB  - Ca-P spots modified zirconia by liquid precursor infiltration and the cell
      responses were investigated. Pre-sintered zirconia specimens were immersed in Ca
      P precursor solution. After dense sintering, scanning electron microscopy showed
      Ca-P spots were formed on the zirconia and anchored with zirconia substrates. The
      distribution density was increased with the extension of immersion time. Energy
      dispersive spectrometer confirmed the stoichiometric Ca/P ratio was about 1.67.
      After hydrothermal treatment, Ca-P spots turned into rod crystals where
      diffraction peaks of tricalcium phosphate and hydroxyapatite were detected by X
      ray diffraction, and Ca2+ and PO43- release decreased slightly (p>0.05). There
      was no significant decrease on three-point bending strength (p>0.05). Osteoblast
      like MC3T3-E1 cells attached and spread well and showed higher proliferation on
      Ca-P spots modified zirconia (p<0.05), though its initial alkaline phosphatase
      activity was not significant high (p>0.05). In conclusion, Ca-P liquid precursor
      infiltration is a potential method to modify the zirconia ceramics for improving
      bioactivity.

PMID- 29375097
TI  - Nucleophagy in Human Disease: Beyond the Physiological Role [Retraction].

PMID- 29375096
TI  - Selective Cerebral Perfusion with the Open Proximal Technique during Descending
      Thoracic or Thoracoabdominal Aortic Repair: An Option of Choice to Reduce
      Neurologic Complications.
AB  - PURPOSE: Selective cerebral perfusion with the open proximal technique for
      thoracoabdominal aortic repair has not been conclusively validated because of its
      procedural complexity and unreliability. We report the clinical outcomes,
      particularly the cerebroneurological complications, of an open proximal procedure
      using selective cerebral perfusion. METHODS: A retrospective chart review
      identified 30 patients between 2007 and 2015 who underwent aortic repair through
      left lateral thoracotomy with selective cerebral perfusion, established through
      endoluminal brachiocephalic and left carotid artery and retrograde left axillary
      artery. RESULTS: The mean durations of the open proximal procedure and cerebral
      ischemia (the duration of the open proximal procedure minus the duration of
      selective cerebral perfusion) were 110.3 +/- 40.1 min and 24.8 +/- 13.0 min,
      respectively. There were two cases (7%) of permanent neurologic dysfunction (PND)
      but no in-hospital deaths. Multivariate analysis identified the duration of
      cerebral ischemia as an independent risk factor for neurologic complications
      including temporary neurologic dysfunction (TND; odds ratio (OR): 1.13; p =
      0.007), but no correlation was found between selective cerebral perfusion
      duration and neurologic complications. CONCLUSION: Despite the relatively long
      duration of the open proximal procedure, selective cerebral perfusion has a
      potential to protect against cerebral complications during thoracic aortic repair
      through a left lateral thoracotomy.

PMID- 29375098
TI  - Evaluation of an innovative oral brush for potential applications using liquid
      based cytology.
AB  - The present study was conducted to assess the applicability of liquid-based
      cytology (LBC) using an innovative oral brush, Orcellex. Fifty healthy volunteers
      were recruited. From each subject, four samples were collected using "Orcellex"
      from apparently normal oral mucosal sites. A plastic spatula was also used to
      obtain an additional sample. Data on the tolerability and acceptability of the
      Orcellex were collected from the subjects, together with assessments of the
      adequacy of LBC slide preparations for cellularity, preparation quality, and the
      types of cells observed. The Orcellex brush was well accepted by the volunteers,
      who reported relatively little pain. Orcellex brush LBC preparations were of good
      quality in terms of cell morphology and staining, with a clean background. Only
      two smears (2/200; 1%) were found to be inadequate due to low cellularity. All of
      the plastic spatula LBC preparations were inadequate. Representative cells from
      all layers of the different oral epithelia examined were documented. Oral liquid
      based cytology using the Orcellex brush may have considerable potential for early
      detection of oral cancer and precancer.

PMID- 29375099
TI  - Simulated localized wear of resin luting cements for universal adhesive systems
      with different curing mode.
AB  - This study evaluated the simulated localized wear of resin luting cements for
      universal adhesive systems using different curing modes. Five resin luting
      cements for universal adhesive systems were evaluated and subsequently subjected
      to wear challenge in a Leinfelder-Suzuki wear simulation device. Overall, 20
      specimens from each resin luting cement were photo-cured for 40 s (dual-cure
      group), and 20 specimens of each material were not photo-cured (chemical-cure
      group). Simulated localized wear was generated using a stainless steel ball
      bearing antagonist in water slurry of polymethylmethacrylate beads. In addition,
      scanning electron microscopy (SEM) observations of resin luting cements and wear
      facets were conducted. Significant differences in simulated wear and SEM
      observations of wear facets were evident among the materials in the dual- and
      chemical-cure groups. The simulated wear and SEM observations of wear facets of G
      CEM LinkForce and Panavia V5 were not influenced by the curing mode. SEM
      observations of resin luting cements were material dependent. In most cases, dual
      curing appears to ensure greater wear resistance of resin luting cements than
      chemical curing alone. The wear resistance of some resin luting cements appears
      to be material dependent and is not influenced by the curing mode.

PMID- 29375100
TI  - Biological evaluation of subgingivally placed direct resin composite materials.
AB  - Placement of composite resin restorations in deep subgingival cavities can damage
      surrounding soft tissues. In addition, commonly used resin-based composites
      (RBCs) might interfere with wound healing and periodontal health. To clarify
      cellular interactions with RBCs, we used an MTT assay to investigate adhesion of
      primary human gingival fibroblasts and human osteoblasts (hFOB 1.19) on five RBC
      materials with and without surface modifications (alumina blasting with 50- or
      110-MUm Al2O3). In addition, high-performance liquid chromatography (HPLC) was
      used to determine release of resin monomers from RBCs after 1 h, 1 day, and 7
      days. As compared with tissue culture plastics (the control), cellular adhesion
      was significantly lower (P < 0.001) for human gingival fibroblasts and
      osteoblasts. Only minor, nonsignificant differences between individual RBCs were
      identified. HPLC analyses identified the release of three bifunctional
      methacrylates bisphenol A glycerolate dimethacrylate, triethylene glycol
      dimethacrylate, and diurethane dimethacrylate from RBCs and showed that monomer
      release increased between 1 h and 1 day but remained low. The present findings
      suggest that surface adhesion in the subgingival area is limited for the tested
      RBCs. Although residual monomer release was low for all tested RBCs, it might be
      sufficient to adversely affect cell adhesion.

PMID- 29375106
TI  - Tricuspid Regurgitation Peak Gradient (TRPG)/Tricuspid Annulus Plane Systolic
      Excursion (TAPSE) - A Novel Parameter for Stepwise Echocardiographic Risk
      Stratification in Normotensive Patients With Acute Pulmonary Embolism.
AB  - BACKGROUND: Patients with intermediate-risk acute pulmonary embolism (APE) are a
      heterogeneous group with an early mortality rate of 2-15%. The tricuspid annulus
      plane systolic excursion (TAPSE) and tricuspid regurgitation peak gradient (TRPG)
      can be used for risk stratification, so we analyzed the prognostic value of a new
      echo parameter (TRPG/TAPSE) for prediction of APE-related 30-day death or need
      for rescue thrombolysis in initially normotensive APE patients.Methods and
      Results:The study group consists of 400 non-high-risk APE patients (191 men, age:
      63.1+/-18.9 years) who had undergone echocardiography within the first 24 h of
      admission. The TRPG/TAPSE parameter was calculated. The clinical endpoint (CE)
      was a combination of 30-day APE-related death and/or rescue thrombolysis. The CE
      occurred in 8 (2%) patients. All patients with TAPSE >=20 mm (n=193, 48.2%) had a
      good prognosis. Among 206 patients with TAPSE <20 mm, 8 cases of the CE occurred
      (3.9%). NPV and PPV for TRPG/TAPSE >4.5 were 0.2 and 0.98, respectively. The CE
      was significantly more frequent in 19 (9.2%) patients with TRPG/TAPSE >4.5 than
      in 188 (90.8%) with TRPG/TAPSE <=4.5 (4 (21.1%) vs. 4 (2.1%), P=0.0005). Among
      normotensive APE patients with TAPSE <20 mm, TRPG/TAPSE >4.5 was associated with
      21.1% risk of APE-related death or rescue thrombolysis. CONCLUSIONS: TRPG/TAPSE,
      a novel echocardiographic parameter, may be useful for stepwise echocardiographic
      risk stratification in normotensive patients with APE, and it identifies patients
      with a poor prognosis.

PMID- 29375107
TI  - Three-Year Follow-up After the Great East Japan Earthquake in the Incidence of
      Out-of-Hospital Cardiac Arrest With Cardiac Origin.
AB  - BACKGROUND: We assessed whether the occurrence of out-of-hospital cardiac arrest
      (OHCA) with cardiac origin increased in the disaster areas during the 3-year
      period after the Great East Japan Earthquake (GEJE).Methods and Results:From the
      OHCA registry in Japan, yearly changes in occurrence after the GEJE were assessed
      by applying Poisson regression models. The risk ratio of the first year after the
      earthquake was significantly greater in both men and women, but the difference
      disappeared in the second and third years. CONCLUSIONS: The GEJE significantly
      increased the occurrence of OHCA with cardiac origin in the first year after the
      earthquake.

PMID- 29375108
TI  - Efficacy and Safety of Figure-of-Eight Suture for Hemostasis After Radiofrequency
      Catheter Ablation for Atrial Fibrillation.
AB  - BACKGROUND: This study evaluated the safety and efficacy of venous figure-of
      eight (FoE) suture to achieve femoral venous hemostasis after radiofrequency (RF)
      catheter ablation (CA) for atrial fibrillation (AF).Methods and Results:We
      retrospectively examined 517 consecutive patients undergoing RFCA for AF. The
      control group (n=247) underwent manual compression for femoral venous hemostasis
      after sheath removal with 6 h of bed rest. The FoE group (n=270) underwent FoE
      suture technique with 4 h of bed rest. All patients achieved successful
      hemostasis within 24 h after CA. Although the incidence of hematoma was similar
      between the groups, the incidence of rebleeding was lower in the FoE group than
      in the control group (FoE vs. control, 3.7% vs. 18.6%, P<0.001). The post
      procedural use of analgesic and/or anti-emetic agents was less frequent in the
      FoE group (19.3% vs. 32.0%, P<0.001). On multiple logistic regression analysis
      after adjustment for age and sex, the use of a vitamin K antagonist (OR, 2.42;
      95% CI: 1.18-4.99, P=0.02) and the FoE suture technique (OR, 0.17; 95% CI: 0.08
      0.35, P<0.001) were independent predictors of rebleeding after CA. CONCLUSIONS:
      FoE suture technique effectively achieved femoral venous hemostasis after RFCA
      for AF. It reduced the risk of rebleeding, shortened bed rest duration, and
      relieved patient discomfort.

PMID- 29375109
TI  - Clinical Outcomes After Treatment with ELCA for In-Stent Restenosis of DES.

PMID- 29375110
TI  - Pravastatin Decreases Infarct Size Induced by Coronary Artery
      Ischemia/Reperfusion with Elevated eNOS Expression in Rats.
AB  - Our previous study showed that pravastatin prevents ischemia and reperfusion
      induced lethal ventricular fibrillation in rats. This study explored whether
      pravastatin decreases myocardial infarct size and this effect is associated with
      endothelial nitric oxide synthase (eNOS) expression in myocardium. Rats were
      treated with ischemia (30 minutes) and reperfusion (60 minutes) after chronic
      oral administration of pravastatin, fluvastatin, or vehicle once daily for 22
      days. Electrocardiograms and blood pressure were continuously recorded,
      myocardial infarct size was measured by TTC-staining, and eNOS expression was
      measured by western blot. The results showed that pravastatin and fluvastatin
      significantly reduced myocardial infarct size. No statistical differences were
      found in the areas at risk among all groups. However, a significant reduction in
      infarct size was observed in three pravastatin groups and one fluvastatin group
      compared to control. Both pravastatin and fluvastatin significantly increased
      eNOS protein expression in ischemic and non-ischemic tissues compared to control.
      Our results suggest that pravastatin decreases cardiovascular mortality beyond
      its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in
      reducing infarct size. These effects may be associated with elevation of eNOS
      expression.

PMID- 29375111
TI  - Cardiac Nestin+ Cells Derived from Early Stage of Dilated Cardiomyopathy Enhanced
      the Survival of the Doxorubicin-Injured Cardiac Muscle HL-1 Cells.
AB  - Dilated cardiomyopathy (DCM), as one of the common cardiomyopathies, is a disease
      of the heart muscle; however, the etiology and pathogenesis of DCM were still
      poorly understood. Nestin has been reported a special marker of stem/progenitor
      cells in various tissues, and the tissue resident Nestin+ cells could promote the
      wound healing and tissue remodeling. However, it remains unclear whether Nestin+
      cells participate in the protection of cardiomyocytes during the pathogenesis of
      DCM. Here the model of mice DCM was induced by doxorubicin (DOX) intraperitoneal
      injection and observed heart failure and ventricular enlargement via
      echocardiography and histologic analysis, respectively. During DCM pathogenesis,
      the number of Nestin+ cells showed a significant peak on day 6 after DOX
      treatment, which then gradually decreases to lower than normal levels after day
      30 in the total population of the heart. Furthermore, we found that the isolated
      increased heart-derived Nestin+ cells are mesenchymal property and could protect
      DOX-induced HL-1 cells toxicity in vitro by promoting their proliferation and
      inhibiting their apoptosis. Collectively, our results showed that Nestin+ cells
      increased during DCM pathogenesis and played an important role in protecting
      against the DOX-induced HL-1 cells loss via regulating proliferation and
      apoptosis. Thus, the loss of Nestin+ cells might be an etiology to DCM
      pathogenesis, and these cells could be a promising candidate cell source for
      study and treatment of DCM patients.

PMID- 29375112
TI  - Coronary Artery Aneurysm Caused by a Stent Fracture.
AB  - Coronary stent fracture (SF) is rare as a complication of percutaneous coronary
      intervention (PCI), and its adverse events are increasingly being recognized with
      the development in devices of PCI. The major adverse events caused by SFs are in
      stent restenosis due to neointimal overgrowth caused by poor drug delivery.1,2) A
      coronary artery aneurysm (CAA) is a rare complication of SF, but may lead to
      lethal events such as acute coronary syndrome or rupture of the CAA further
      leading to cardiac tamponade.3-5) However, the management of CAAs is
      controversial with or without SF.6) Herein, we report a case of a CAA caused by
      an SF and discuss the management of CAA complicated with SF, along with a
      literature review. We suggest that surgical treatment should be considered the
      higher-priority strategy in the cases of CAA with SF as compared to CAA without
      SF.

PMID- 29375113
TI  - Various Cardiac Abnormalities Caused by Bacterial Myocarditis.
AB  - A 69-year-old woman without any past disease history was hospitalized for heart
      failure. After hospitalization, she showed myocardial infarction,
      atrioventricular dissociation, and cardiac dysfunction, and finally she passed
      away despite intensive care. Autopsy revealed that the cardiac abnormalities were
      due to bacterial myocarditis possibly resulting from urinary tract infection by
      E. coli. Although bacterial myocarditis is rare in developed countries, we should
      consider its possibility when patients show various cardiac abnormalities with
      bacterial infection.

PMID- 29375114
TI  - A Case of Left Atrial Myxoma Whose Initial Symptom Was Finger Ischemic Symptom.
AB  - We experienced a 45-year-old Japanese man who was transferred to our hospital
      complaining of acute onset of pain and pallor in the right lower limb. Two years
      earlier, he had complained of repetitive pain at rest and pallor in the left
      third and fourth fingers. The physical exam and angiography demonstrated
      occlusion of finger arteries, however we could not reach final diagnosis. Acute
      arterial occlusive disease in the right lower limb was suspected. Transthoracic
      echocardiography demonstrated a gross tumor in the left atrium, which suggested
      left atrial myxoma. An emergency tumorectomy was successfully conducted.
      Pathologically, the fragile tumor and resultant thrombosis could have caused the
      patient's peripheral circulatory failure at least two years prior to this
      episode. A rigorous systemic survey is important even when the ischemic symptom
      is localized in peripheral circulation.

PMID- 29375115
TI  - Can Anti-inflammatory Therapy Prevent Atrial Fibrillation in Myocardial
      Infarction Patients?

PMID- 29375116
TI  - Toll-Like Receptors 2 and 4 Predict New-Onset Atrial Fibrillation in Acute
      Myocardial Infarction Patients.
AB  - Myocardial infarction (MI) can cause new-onset atrial fibrillation (AF) due to
      cardiac remodeling. As a recent study has shown, inflammatory factors are closely
      tied to cell death and survival in myocardial ischemia injury. Toll-like
      receptors (TLRs) have been shown to participate in the process of myocardial
      infarction as innate immune factors.The subjects were divided into 3 groups:
      healthy controls (n = 82), MI patients (n = 84), and AFMI (new-onset atrial
      fibrillation after myocardial infarction) patients (n = 85). Peripheral blood
      mononuclear cell (PBMC) TLR mRNA expression was detected by rt-PCR. Western blot
      was used to analyze PBMC TLRs and their downstream signal protein expression.
      PBMCs were presented as TLR2 expression or TLR4 expression using flow
      cytometry.From mRNA to protein detection, PBMC TLR2 and TLR4 were significantly
      higher in the AFMI group than in the control group and MI group. A similar
      tendency was also observed in the expression of downstream signaling proteins.
      When further analyzed with TLR2 and TLR4 antibodies by flow cytometry, PBMC
      levels also appeared to be higher in AFMI patients than those in MI patients and
      the healthy control group.In our study, PBMC TLRs and their downstream signaling
      proteins were significantly higher in the acute myocardial infarction patients
      with new-onset atrial fibrillation compared with healthy people and acute
      myocardial infarction patients without new-onset atrial fibrillation. They have
      the potential to be novel biomarkers for new-onset atrial fibrillation after
      acute myocardial infarction.

PMID- 29375117
TI  - Tolvaptan Improves Prognosis in Responders with Acute Decompensated Heart Failure
      by Reducing the Dose of Loop Diuretics.
AB  - It is unknown whether a response to tolvaptan (TLV) is related to prognosis in
      patients with acute decompensated heart failure (ADHF). We selected 25 patients
      as responders by their urinary response to TLV and by reduction of loop diuretics
      from 37 consecutive ADHF patients treated with TLV. As a control group, we
      selected 25 patients from 100 consecutive ADHF patients who were not treated with
      TLV by propensity score matching for age, serum sodium level, serum creatinine
      level, plasma B-type natriuretic peptide (BNP) level, systolic blood pressure,
      heart rate, and dose of loop diuretics. The primary outcome was defined as a
      composite endpoint of mortality and/or hemodialysis. The amount of loop diuretics
      administered to responders was reduced by TLV from 68.8 +/- 26.2 mg to 30.4 +/-
      18.6 mg of furosemide equivalents per day, whereas the loop diuretic dose
      administered to non-responders was increased. The event-free survival of the TLV
      responders during 20 months was significantly better than that of the control
      group (95.8% versus 68.4%, P = 0.0406). The TLV responders, plasma BNP level, and
      estimated glomerular filtration rate were significantly related to the events in
      the Cox proportional hazard analysis. Patients with ADHF who respond to TLV may
      have a better prognosis than propensity-matched patients not receiving TLV
      treatment. In TLV responders, it may be possible to improve the patient's
      prognosis if the dose of loop diuretics can be reduced with TLV therapy.

PMID- 29375118
TI  - Comparison of Swirl Sign and Black Hole Sign in Predicting Early Hematoma Growth
      in Patients with Spontaneous Intracerebral Hemorrhage.
AB  - BACKGROUND Early hematoma growth is associated with poor outcome in patients with
      spontaneous intracerebral hemorrhage (ICH). The swirl sign (SS) and the black
      hole sign (BHS) are imaging markers in ICH patients. The aim of this study was to
      compare the predictive value of these 2 signs for early hematoma growth. MATERIAL
      AND METHODS ICH patients were screened for the appearance of the 2 signs within 6
      h after onset of symptoms. The sensitivity, specificity, positive predictive
      value (PPV), and negative predictive value (NPV) of the 2 signs in predicting
      early hematoma growth were assessed. The accuracy of the 2 signs in predicting
      early hematoma growth was analyzed by receiver-operator analysis. RESULTS A total
      of 200 patients were enrolled in this study. BHS was found in 30 (15%) patients,
      and SS was found in 70 (35%) patients. Of the 71 patients with early hematoma
      growth, BHS was found on initial computed tomography scans in 24 (33.8%) and SS
      in 33 (46.5%). The sensitivity, specificity, PPV, and NPV of BHS for predicting
      early hematoma growth were 33.8%, 95.3%, 80.0%, and 72.0%, respectively. The
      sensitivity, specificity, PPV, and NPV of SS were 46.5%, 71.3%, 47.0%, and 71.0%,
      respectively. The area under the curve was 0.646 for BHS and 0.589 for SS
      (P=0.08). Multivariate logistic regression showed that presence of BHS is an
      independent predictor of early hematoma growth. CONCLUSIONS The Black hole sign
      seems to be good predictor for hematoma growth. The presence of swirl sign on
      admission CT does not independently predict hematoma growth in patients with ICH.

PMID- 29375119
TI  - Massive Rhabdomyolysis; A Rare Cause of Hepatocellular Dysfunction.
AB  - BACKGROUND Rhabdomyolysis syndrome is a rare surgical complication. It is
      infrequently reported in prolonged operations under lateral decubitus position.
      This syndrome mainly impacts kidney function and electrolytes levels; liver is
      another organ that is uncommonly affected. CASE REPORT A 54-year-old male
      underwent a partial hepatectomy in the supine position, the procedure lasted
      three hours. After five days of uneventful recovery from surgery, he was
      readmitted to the hospital with rhabdomyolysis syndrome involving his lower
      limbs. No predisposing factors other than surgery could be identified. Based on
      blood tests, the only affected organ was the liver. Upon aggressive hydration,
      the creatinine kinase, hepatic enzymes, bilirubin levels, and prothrombin time
      were normalized. The patient regained normal physical strength over the next few
      weeks. CONCLUSIONS Liver dysfunction secondary to rhabdomyolysis is rare but
      should be considered when other causes are excluded. Prothrombin time, bilirubin
      levels and albumin levels may help to identify concomitant liver damage.
      Rhabdomyolysis is rarely reported in liver resection surgeries.

PMID- 29375120
TI  - The structure, expression, and multifaceted role of immune-checkpoint protein
      VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and
      inflammation.
AB  - Among various immunoregulatory molecules, the B7 family of immune-checkpoint
      receptors consists of highly valuable targets for cancer immunotherapy.
      Antibodies targeting two B7 family co-inhibitory receptors, CTLA-4 and PD-1, have
      elicited long-term clinical outcomes in previously refractory cancer types and
      are considered a breakthrough in cancer therapy. Despite the success, the
      relatively low response rate (20-30%) warrants efforts to identify and overcome
      additional immune-suppressive pathways. Among the expanding list of T cell
      inhibitory regulators, V domain immunoglobulin suppressor of T cell activation
      (VISTA) is a unique B7 family checkpoint that regulates a broad spectrum of
      immune responses. Here, we summarize recent advances that highlight the
      structure, expression, and multi-faceted immunomodulatory mechanisms of VISTA in
      the context of autoimmunity, inflammation, and anti-tumor immunity.

PMID- 29375122
TI  - AIM associated with the IgM pentamer: attackers on stand-by at aircraft carrier.
AB  - Circulating immunoglobulin M (IgM) exists in a pentameric form, possessing a
      polyreactive nature that responds not only to foreign antigens but also to
      autoantigens; thus, it is involved in both beneficial and detrimental immune
      responses, including protection from infection and the progression of
      autoimmunity. On the other hand, IgM also behaves as a carrier of the apoptosis
      inhibitor of macrophage (AIM) protein, storing a large amount of the inactivated
      form of AIM in the blood through this association. Under different disease
      conditions, AIM can dissociate from IgM locally or systemically to exert its
      function, inducing the removal of various biological debris such as excess fat,
      bacteria, cancer cells or dead cell debris. Most typically, upon induction of
      acute kidney injury (AKI), IgM-free AIM is filtered by the glomerulus in the
      kidney, which stimulates the clearance of intraluminal dead cells debris at the
      obstructed proximal tubules, thereby facilitating the repair of kidney injury.
      Interestingly, cats exhibit a deficiency in AIM release from IgM, which may
      increase their susceptibility to renal failure. Conversely, association with AIM
      inhibits IgM binding to the Fcalpha/MU receptor on follicular dendritic cells at
      the splenic germinal center, thereby protecting the IgM immune complex from
      Fcalpha/MU receptor-mediated internalization, which supports IgM-dependent
      antigen presentation to B cells and stimulates high-affinity IgG antibody
      production. The regulation of AIM-IgM binding, resulting from the discovery of
      reciprocal actions between AIM and IgM, could lead to the development of novel
      therapies against different diseases.

PMID- 29375125
TI  - Inhibition of neddylation ameliorates DSS-induced colitis.

PMID- 29375121
TI  - Guillain-Barre syndrome, transverse myelitis and infectious diseases.
AB  - Guillain-Barre syndrome (GBS) and transverse myelitis (TM) both represent
      immunologically mediated polyneuropathies of major clinical importance. Both are
      thought to have a genetic predisposition, but as of yet no specific genetic risk
      loci have been clearly defined. Both are considered autoimmune, but again the
      etiologies remain enigmatic. Both may be induced via molecular mimicry,
      particularly from infectious agents and vaccines, but clearly host factor and co
      founding host responses will modulate disease susceptibility and natural history.
      GBS is an acute inflammatory immune-mediated polyradiculoneuropathy characterized
      by tingling, progressive weakness, autonomic dysfunction, and pain. Immune injury
      specifically takes place at the myelin sheath and related Schwann-cell components
      in acute inflammatory demyelinating polyneuropathy, whereas in acute motor axonal
      neuropathy membranes on the nerve axon (the axolemma) are the primary target for
      immune-related injury. Outbreaks of GBS have been reported, most frequently
      related to Campylobacter jejuni infection, however, other agents such as Zika
      Virus have been strongly associated. Patients with GBS related to infections
      frequently produce antibodies against human peripheral nerve gangliosides. In
      contrast, TM is an inflammatory disorder characterized by acute or subacute
      motor, sensory, and autonomic spinal cord dysfunction. There is interruption of
      ascending and descending neuroanatomical pathways on the transverse plane of the
      spinal cord similar to GBS. It has been suggested to be triggered by infectious
      agents and molecular mimicry. In this review, we will focus on the putative role
      of infectious agents as triggering factors of GBS and TM.

PMID- 29375123
TI  - The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?
AB  - Macrophages are one of the most abundant leukocyte populations infiltrating tumor
      tissues and can exhibit both tumoricidal and tumor-promoting activities. In 1989,
      we reported the purification of monocyte chemoattractant protein-1 (MCP-1) from
      culture supernatants of mitogen-activated peripheral blood mononuclear cells and
      tumor cells. MCP-1 is a potent monocyte-attracting chemokine, identical to the
      previously described lymphocyte-derived chemotactic factor or tumor-derived
      chemotactic factor, and greatly contributes to the recruitment of blood monocytes
      into sites of inflammatory responses and tumors. Because in vitro-cultured tumor
      cells often produce significant amounts of MCP-1, tumor cells are considered to
      be the main source of MCP-1. However, various non-tumor cells in the tumor stroma
      also produce MCP-1 in response to stimuli. Studies performed in vitro and in vivo
      have provided evidence that MCP-1 production in tumors is a consequence of
      complex interactions between tumor cells and non-tumor cells and that both tumor
      cells and non-tumor cells contribute to the production of MCP-1. Although MCP-1
      production was once considered to be a part of host defense against tumors, it is
      now believed to regulate the vicious cycle between tumor cells and macrophages
      that promotes the progression of tumors.

PMID- 29375124
TI  - IDO1 in cancer: a Gemini of immune checkpoints.
AB  - Indoleamine 2, 3-dioxygenase 1 (IDO1) is a rate-limiting metabolic enzyme that
      converts the essential amino acid tryptophan (Trp) into downstream catabolites
      known as kynurenines. Coincidently, numerous studies have demonstrated that IDO1
      is highly expressed in multiple types of human cancer. Preclinical studies have
      further introduced an interesting paradox: while single-agent treatment with IDO1
      enzyme inhibitor has a negligible effect on decreasing the established cancer
      burden, approaches combining select therapies with IDO1 blockade tend to yield a
      synergistic benefit against tumor growth and/or animal subject survival. Given
      the high expression of IDO1 among multiple cancer types along with the lack of
      monotherapeutic efficacy, these data suggest that there is a more complex
      mechanism of action than previously appreciated. Similar to the dual faces of the
      astrological Gemini, we highlight the multiple roles of IDO1 and review its
      canonical association with IDO1-dependent tryptophan metabolism, as well as
      documented evidence confirming the dispensability of enzyme activity for its
      immunosuppressive effects. The gene transcript levels for IDO1 highlight its
      strong association with T-cell infiltration, but the lack of a universal
      prognostic significance among all cancer subtypes. Finally, ongoing clinical
      trials are discussed with consideration of IDO1-targeting strategies that enhance
      the efficacy of immunotherapy for cancer patients.

PMID- 29375127
TI  - Proteomic analysis reveals distinctive protein profiles involved in CD8+ T cell
      mediated murine autoimmune cholangitis.
AB  - Autoimmune cholangitis arises from abnormal innate and adaptive immune responses
      in the liver, and T cells are critical drivers in this process. However, little
      is known about the regulation of their functional behavior during disease
      development. We previously reported that mice with T cell-restricted expression
      of a dominant negative form of transforming growth factor beta receptor type II
      (dnTGFbetaRII) spontaneously develop an autoimmune cholangitis that resembles
      human primary biliary cholangitis (PBC). Adoptive transfer of CD8+ but not CD4+ T
      cells into Rag1-/- mice reproduced the disease, demonstrating a critical role for
      CD8+ T cells in PBC pathogenesis. Herein, we used SOMAscan technology to perform
      proteomic analysis of serum samples from dnTGFbetaRII and B6 control mice at
      different ages. In addition, we analyzed CD8 protein profiles after adoptive
      transfer of splenic CD8+ cells into Rag1-/- recipients. The use of the unique
      SOMAscan aptamer technology revealed critical and distinct profiles of CD8 cells,
      which are key to biliary mediation. In total, 254 proteins were significantly
      increased while 216 proteins were significantly decreased in recipient hepatic
      CD8+ cells compared to donor splenic CD8+ cells. In contrast to donor splenic
      CD8+ cells, recipient hepatic CD8+ cells expressed distinct profiles for proteins
      involved in chemokine signaling, focal adhesion, T cell receptor and natural
      killer cell-mediated cytotoxicity pathways.

PMID- 29375130
TI  - CD8+CD28- T cells: not only age-related cells but a subset of regulatory T cells.

PMID- 29375126
TI  - Chemokines in homeostasis and diseases.
AB  - For the past twenty years, chemokines have emerged as a family of critical
      mediators of cell migration during immune surveillance, development, inflammation
      and cancer progression. Chemokines bind to seven transmembrane G protein-coupled
      receptors (GPCRs) that are expressed by a wide variety of cell types and cause
      conformational changes in trimeric G proteins that trigger the intracellular
      signaling pathways necessary for cell movement and activation. Although
      chemokines have evolved to benefit the host, inappropriate regulation or
      utilization of these small proteins may contribute to or even cause diseases.
      Therefore, understanding the role of chemokines and their GPCRs in the complex
      physiological and diseased microenvironment is important for the identification
      of novel therapeutic targets. This review introduces the functional array and
      signals of multiple chemokine GPCRs in guiding leukocyte trafficking as well as
      their roles in homeostasis, inflammation, immune responses and cancer.

PMID- 29375129
TI  - Immunological roulette: Luck or something more? Considering the connections
      between host and environment in TB.
AB  - Accurate prediction of which patient will progress from a sub-clinical
      Mycobacterium tuberculosis infection to active tuberculosis represents an
      elusive, yet critical, clinical research objective. From the individual
      perspective, progression can be considered to be the product of a series of
      unfortunate events or even a run of bad luck. Here, we identify the subtle
      physiological relationships that can influence the odds of progression to active
      TB and how this progression may reflect directed dysbiosis in a number of
      interrelated systems. Most infected individuals who progress to disease have
      apparently good immune responses, but these responses are, at times, compromised
      by either local or systemic environmental factors. Obvious disease promoting
      processes, such as tissue-damaging granulomata, usually manifest in the lung, but
      illness is systemic. This apparent dichotomy between local and systemic reflects
      a clear need to define the factors that promote progression to active disease
      within the context of the body as a physiological whole. We discuss aspects of
      the host environment that can impact expression of immunity, including the
      microbiome, glucocorticoid-mediated regulation, catecholamines and interaction
      between the gut, liver and lung. We suggest the importance of integrating
      precision medicine into our analyses of experimental outcomes such that
      apparently conflicting results are not contentious, but rather reflect the impact
      of these subtle relationships with our environment and microbiota.

PMID- 29375128
TI  - Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity.
AB  - B cells have a critical role in the initiation and acceleration of autoimmune
      diseases, especially those mediated by autoantibodies. In the peripheral lymphoid
      system, mature B cells are activated by self or/and foreign antigens and signals
      from helper T cells for differentiating into either memory B cells or antibody
      producing plasma cells. Accumulating evidence has shown that epigenetic
      regulations modulate somatic hypermutation and class switch DNA recombination
      during B-cell activation and differentiation. Any abnormalities in these complex
      regulatory processes may contribute to aberrant antibody production, resulting in
      autoimmune pathogenesis such as systemic lupus erythematosus. Newly generated
      knowledge from advanced modern technologies such as next-generation sequencing,
      single-cell sequencing and DNA methylation sequencing has enabled us to better
      understand B-cell biology and its role in autoimmune development. Thus this
      review aims to summarize current research progress in epigenetic modifications
      contributing to B-cell activation and differentiation, especially under
      autoimmune conditions such as lupus, rheumatoid arthritis and type 1 diabetes.

PMID- 29375132
TI  - Stimulation of TNF receptor type 2 expands regulatory T cells and ameliorates
      established collagen-induced arthritis in mice.
AB  - Tumor necrosis factor (TNF) and its receptors TNF receptor type 1 (TNFR1) and
      type 2 (TNFR2) have a central role in chronic inflammatory diseases. While TNFR1
      mainly confers inflammation, activation of TNFR2 elicits not only pro
      inflammatory but also anti-inflammatory effects. In this study, we wanted to
      investigate the anti-inflammatory therapeutic potential of selective activation
      of TNFR2 in mice with established collagen-induced arthritis. Mice with
      established arthritis induced by immunization with bovine collagen type II were
      treated with six injections of the TNFR2-specific agonist TNCscTNF80, given every
      second day. Two days after treatment cessation, the cell compositions of bone
      marrow, spleen and lymph nodes were analyzed. Mice were visually scored until day
      30 after the start of therapy and the degree of joint inflammation was determined
      by histology. Treatment with TNCscTNF80 increased arthritis-induced myelopoiesis.
      Little effect was seen on the infiltration rate of inflammatory immature myeloid
      cells and on the reduction of lymphoid cells in secondary lymphoid organs. Upon
      treatment, frequency of regulatory T (Treg) cells in the CD4+ T-cell population
      was increased in both spleen and inguinal lymph nodes. In addition, the
      expression of TNFR2 on Treg cells was enhanced. The clinical score started to
      improve 1 week after cessation treatment and remained lower 30 days after
      initiation of therapy. The histological score also revealed amelioration of joint
      inflammation in TNCscTNF80-treated versus control mice. Activation of TNFR2 might
      provide a suitable therapeutic strategy in autoimmune arthritis by increasing the
      numbers of regulatory cell types, in particular Treg cells, and by attenuation of
      arthritis.Cellular and Molecular Immunology advance online publication, 29
      January 2018; doi:10.1038/cmi.2017.138.

PMID- 29375134
TI  - Biography of Professor Nicolaou: a journey to the extremes of molecular
      complexity.

PMID- 29375131
TI  - A modified HLA-A*0201-restricted CTL epitope from human oncoprotein (hPEBP4)
      induces more efficient antitumor responses.
AB  - We previously identified human phosphatidylethanolamine-binding protein 4
      (hPEBP4) as an antiapoptotic protein with increased expression levels in breast,
      ovarian and prostate cancer cells, but low expression levels in normal tissues,
      which makes hPEBP4 an attractive target for immunotherapy. Here, we developed
      hPEBP4-derived immunogenic peptides for inducing antigen-specific cytotoxic T
      lymphocytes (CTLs) targeting breast cancer. A panel of hPEBP4-derived peptides
      predicted by peptide-MHC-binding algorithms was evaluated to characterize their
      HLA-A2.1 affinity and immunogenicity. We identified a novel immunogenic peptide,
      P40-48 (TLFCQGLEV), that was capable of eliciting specific CTL responses in HLA
      A2.1/Kb transgenic mice, as well as in peripheral blood lymphocytes from breast
      cancer patients. Furthermore, amino-acid substitutions in the P40-48 sequence
      improved its immunogenicity against hPEBP4, a self-antigen, thus circumventing
      tolerance. We designed peptide analogs by preferred auxiliary HLA-A*0201 anchor
      residue replacement, which induced CTLs that were crossreactive to the native
      peptide. Several analogs were able to stably bind to HLA-A*0201 and elicit
      specific CTL responses better than the native sequence. Importantly, adoptive
      transfer of CTLs induced by vaccination with two analogs more effectively
      inhibited tumor growth than the native peptide. These data indicate that peptide
      analogs with high immunogenicity represent promising candidates for peptide
      mediated therapeutic cancer vaccines.

PMID- 29375133
TI  - Tumor necrosis factor: The key to hepatitis B viral clearance.

PMID- 29375135
TI  - Total synthesis of (+)-lysergic acid.
AB  - A total synthesis of (+)-lysergic acid, which features the C-C bond formation
      between C10 and C11 via cleavage of an aziridine ring, was accomplished.

PMID- 29375137
TI  - Professor KC Nicolaou expanded the world of synthetic organic chemistry by total
      synthesis and his laboratories have fostered many talented researchers.

PMID- 29375136
TI  - Corrigendum: Total synthesis and absolute configuration of avenolide,
      extracellular factor in Streptomyces avermitilis.
AB  - This corrects the article DOI: 10.1038/ja.2011.90.

PMID- 29375138
TI  - Corrigendum: Microbial metabolites and derivatives targeted at inflammation and
      bone diseases therapy: chemistry, biological activity and pharmacology.
AB  - This corrects the article DOI: 10.1038/ja.2017.138.

PMID- 29375140
TI  - The market for chimeric antigen receptor T cell therapies.

PMID- 29375141
TI  - Reperfusion after pulmonary embolism - long-term follow-up, risk factors,
      clinical impact.
AB  - BACKGROUND AND AIM: Thromboembolic disease is the third most common
      cardiovascular disorder and deep vein thrombosis carries the risk of pulmonary
      embolism (PE). Questions related to reperfusion after PE remain, especially risk
      factors. Incomplete reperfusion after PE is closely related to the development of
      chronic thromboembolic pulmonary hypertension. The aim of this study was to
      determine the relation between reperfusion after PE in the long term over a
      period of 24 months, laboratory results and clinical risk factors found during
      the initial PE event. PATIENTS AND METHODS: 85 consecutive patients with a first
      episode of acute PE, diagnosed at 4 cardiology clinics, were followed up using
      clinical evaluation, scintigraphy and echocardiography (6, 12 and 24 months after
      the PE. 35 patients were in the low risk category (41%), 42 (49%) in the
      intermediate risk group and 8 (9%) in the high risk category. RESULTS: Perfusion
      defects persisted in 20 patients (26%) after 6 months, in 19 patients (25%) after
      12 months and in 14 patients (19%) after 24 months. The incidence was more
      frequent in older patients, with more serious (higher risk) PE, increased right
      ventricular internal diameter during the initial episode, and more significant
      tricuspid insufficiency in the initial echocardiography. Notably, higher
      hemoglobin levels were also shown as a significant risk factor. The presence of
      perfusion defects after 24 months correlated with a concurrent higher pulmonary
      pressure but not with either patient function or adverse events (recurrence of
      PE, re-hospitalization or bleeding). In 3 cases (4% of patients), long-term
      echocardiographic evidence of pulmonary hypertension was detected. CONCLUSION:
      Even after 24 months from acute PE with adequate anticoagulation treatment,
      incomplete reperfusion was found in 19% of patients with a corresponding risk of
      chronic thromboembolic pulmonary disease and hypertension.

PMID- 29375142
TI  - A SEARCH FOR LOST PLANETS IN THE KEPLER MULTI-PLANET SYSTEMS AND THE DISCOVERY OF
      A LONG PERIOD, NEPTUNE-SIZED EXOPLANET KEPLER-150 F.
AB  - The vast majority of the 4700 confirmed planets and planet candidates discovered
      by the Kepler space telescope were first found by the Kepler pipeline. In the
      pipeline, after a transit signal is found, all data points associated with those
      transits are removed, creating a "Swiss cheese"-like light curve full of holes,
      which is then used for subsequent transit searches. These holes could render an
      additional planet undetectable (or "lost"). We examine a sample of 114 stars with
      3+ confirmed planets to see the effect that this "Swiss cheesing" may have. A
      simulation determined that the probability that a transiting planet is lost due
      to the transit masking is low, but non-neglible, reaching a plateau at ~3.3% lost
      in the period range of P = 400 - 500 days. We then model the transits in all
      quarters of each star and subtract out the transit signals, restoring the in
      transit data points, and use the Kepler pipeline to search the transit-subtracted
      (i.e., transit-cleaned) light curves. However, the pipeline did not discover any
      credible new transit signals. This demonstrates the validity and robustness of
      the Kepler pipeline's choice to use transit masking over transit subtraction.
      However, a follow-up visual search through all the transit-subtracted data, which
      allows for easier visual identification of new transits, revealed the existence
      of a new, Neptune-sized exoplanet. Kepler-150 f (P = 637.2 days, RP = 3.86 R?) is
      confirmed using a combination of false positive probability analysis, transit
      duration analysis, and the planet multiplicity argument.

PMID- 29375143
TI  - Intergenerational Exchanges in Mexico: Types and Intensity of Support.
AB  - This article analyses exchanges of support between the elderly and adult
      generations and by gender, based on data from the United Nations household survey
      in Mexico City (SABE, 2000), and the National Study of Ageing and Health (ENASEM,
      2001). Results indicate that in Mexico both generations - elderly parents and
      adult children - provide support, such as money, services, care or gifts for
      grandchildren, according to gender roles and the generation's resources. Men
      provide monetary support and reproduce their role as family providers, but this
      role depends on having an income from work and, in later years, a pension, a more
      common situation among men than among women. Women develop their female domestic
      role as caregivers. They do not have a formal income, but receive informal
      economic support and offer services and care to their relatives, reproducing
      their invisible and unpaid work during their life course. Both types of support
      are widely exchanged between elderly parents and adult children and children-in
      law.

PMID- 29375139
TI  - Post-exposure treatments for Ebola and Marburg virus infections.
AB  - The filoviruses - Ebola virus and Marburg virus - cause lethal haemorrhagic fever
      in humans and non-human primates (NHPs). Filoviruses present a global health
      threat both as naturally acquired diseases and as potential agents of
      bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising
      therapies for post-exposure use with demonstrated efficacy in the gold-standard
      NHP models of filovirus disease were unable to show statistically significant
      protection in patients infected with Ebola virus. This Review briefly discusses
      these failures and what has been learned from these experiences, and summarizes
      the current status of post-exposure medical countermeasures in development,
      including antibodies, small interfering RNA and small molecules. We outline how
      our current knowledge could be applied to the identification of novel
      interventions and ways to use interventions more effectively.

PMID- 29375145
TI  - Is Breast Surgery Necessary for Breast Carcinoma in Complete Remission Following
      Neoadjuvant Chemotherapy?
AB  - The likelihood of pathological complete remission (pCR) of breast cancer
      following neoadjuvant chemotherapy (NACT) is increasing; most of all in the
      triple negative and HER2 positive tumour subgroups. The question thus arises
      whether or not breast surgery is necessary when there is complete remission after
      NACT, and whether it provides any improvement of the oncological treatment result
      when tumour is no longer detectable. Avoiding surgery and possibly even
      radiotherapy would only be conceivable on the basis of a reliable diagnosis of
      pCR without operating. Current imaging does not achieve the necessary sensitivity
      and specificity to assure the diagnosis of pathological complete remission.
      Further studies are therefore required to determine which methods are best able
      to evaluate tumour response to NACT. Studies on image-guided, minimally invasive
      biopsies after NACT have delivered first promising results towards diagnosing pCR
      before surgery and could provide the basis for further studies on the possibility
      of avoiding surgery in this specific patient collective.

PMID- 29375144
TI  - Intrauterine Growth Restriction. Guideline of the German Society of Gynecology
      and Obstetrics (S2k-Level, AWMF Registry No. 015/080, October 2016).
AB  - Aims: The aim of this official guideline published and coordinated by the German
      Society of Gynecology and Obstetrics (DGGG) was to provide consensus-based
      recommendations obtained by evaluating the relevant literature for the diagnostic
      treatment and management of women with fetal growth restriction. Methods: This
      S2k guideline represents the structured consensus of a representative panel of
      experts with a range of different professional backgrounds commissioned by the
      Guideline Committee of the DGGG. Recommendations: Recommendations for diagnostic
      treatment, management, counselling, prophylaxis and screening are presented.

PMID- 29375146
TI  - Role of Indocyanine Green in Fluorescence Imaging with Near-Infrared Light to
      Identify Sentinel Lymph Nodes, Lymphatic Vessels and Pathways Prior to Surgery -
      A Critical Evaluation of Options.
AB  - Modern surgical strategies aim to reduce trauma by using functional imaging to
      improve surgical outcomes. This reviews considers and evaluates the importance of
      the fluorescent dye indocyanine green (ICG) to visualize lymph nodes, lymphatic
      pathways and vessels and tissue borders in an interdisciplinary setting. The work
      is based on a selective search of the literature in PubMed, Scopus, and Google
      Scholar and the authors' own clinical experience. Because of its simple,
      radiation-free and uncomplicated application, ICG has become an important
      clinical indicator in recent years. In oncologic surgery ICG is used extensively
      to identify sentinel lymph nodes with promising results. In some studies, the
      detection rates with ICG have been better than the rates obtained with
      established procedures. When ICG is used for visualization and the quantification
      of tissue perfusion, it can lead to fewer cases of anastomotic insufficiency or
      transplant necrosis. The use of ICG for the imaging of organ borders, flap plasty
      borders and postoperative vascularization has also been scientifically evaluated.
      Combining the easily applied ICG dye with technical options for intraoperative
      and interventional visualization has the potential to create new functional
      imaging procedures which, in future, could expand or even replace existing
      established surgical techniques, particularly the techniques used for sentinel
      lymph node and anastomosis imaging.

PMID- 29375147
TI  - Letrozole vs. Placebo Pretreatment in the Medical Management of First Trimester
      Missed Miscarriage: a Randomized Controlled Trial.
AB  - Introduction: Misoprostol is used for the medical management of miscarriage as it
      is more effective in the early stages of pregnancy. Letrozole has an anti
      estrogen effect and is used for the pretreatment of miscarriage with misoprostol.
      Aim: The aim of this study was compare the efficacy and safety of letrozole with
      placebo pretreatment in the medical management of first trimester missed
      miscarriage. Design: This was a prospective randomized case-control study.
      Patients and Methods: Four hundred and thirty-eight women were randomly divided
      into two groups of 219; the placebo group received placebo tablets twice daily
      for 3 days, followed by 800 micrograms of misoprostol vaginally on the fourth day
      of enrolment, while the letrozole group received letrozole 10 mg twice daily for
      three days followed by 800 micrograms misoprostol administered vaginally.
      Symptoms and side effects were recorded, and the women advised to return to
      hospital if they experienced severe pain or bleeding or intolerable side effects
      and to report to hospital for a check-up one week after misoprostol
      administration. Ultrasound was done seven days after misoprostol administration
      to monitor outcomes. Surgical evacuation was carried out if medical management
      failed. Results: There were significant differences between the two groups, with
      better outcomes found for the letrozole group in terms of rates of complete
      miscarriage, onset of vaginal bleeding, and interval between induction and onset
      of expulsion (p < 0.001). A higher rate of nausea and vomiting was reported for
      the letrozole group (p = 0.002). Differences between groups with regard to pre-
      and post-termination hemoglobin levels, fever, severe pain and severe bleeding
      needing evacuation were not statistically significant. Conclusion: Adding
      letrozole to misoprostol improves the success rate and decreases the interval
      between induction and expulsion in cases of first trimester miscarriage; however,
      nausea and vomiting is higher with letrozole.

PMID- 29375148
TI  - Comparison of Four Methods of Treating Ectopic Pregnancy: A Retrospective Cohort
      Study.
AB  - Objective: To compare the results of expectant management, single and multidose
      methotrexate (MTX) and surgical management of ectopic pregnancy (EP). Materials
      and Methods: In this retrospective cohort study, the original files of 233
      patients who were treated for EP between May 2009 and December 2016 were
      analyzed. The patients were assigned to the following groups based on the applied
      treatment methods: Group 1, expectant management (n = 24), Group 2, single-dose
      MTX (n = 144), Group 3, multiple-dose MTX (n = 25), and Group 4, surgical
      intervention (n = 40). The following parameters were recorded and assessed:
      sociodemographic characteristics, pelvic ultrasonography findings (gestational
      sac, ectopic mass appearance, positive fetal cardiac activity), serum beta-human
      chorionic gonadotropin (beta-hCG) levels on Day 0, Day 4, and Day 7, and surgical
      procedures in women that underwent surgical interventions. Results: The
      sociodemographic characteristics were similar in all four groups. The percentage
      of ectopic mass and positive fetal cardiac activity was greater and the diameter
      of the mass was larger in Group 4 than in the other groups. The beta-hCG values
      on Day 0, Day 4, and Day 7 were statistically different between the groups (p <
      0.001). The cutoff value for the beta-hCG change for EP resolution was 18%
      between Day 0 and Day 4 (AUC = 0.726, p < 0.001) and 15% between Day 4 and Day 7
      (AUC = 0.874, p < 0.001). The probability of the requirement for an additional
      dose of MTX was 0.78 (95% CI 0.71 - 0.87; p < 0.001) times lower in patients who
      had a > 18% decrease in beta-hCG levels from Day 0 to Day 4 in comparison to
      those who had a decrease < 18% from Day 0 to Day 4. The probability of the
      requirement for an additional dose of MTX was 1.64 (95% CI 1.25 - 2.16; p <
      0.001) times greater in patients whose reduction in beta-hCG levels from Day 4 to
      Day 7 was < 15% in comparison to those who had > 15% reduction from Day 4 to Day
      7. Conclusions: Additional dose requirements for patients with EP may be
      predicted early in the changes in beta-hCG levels between Day 0 and Day 4.
      Further prospective studies are required to elucidate this issue.

PMID- 29375150
TI  - Local field effect on charge-capture/emission dynamics.
AB  - Charge-capture/emission is ubiquitous in electron devices. Its dynamics often
      play critical roles in device operation and reliability. Treatment of this basic
      process is found in many text books and is considered well understood. As in many
      electron device models, the individuality of immobile charge is commonly replaced
      with the average quantity of charge density. This has worked remarkably well when
      large numbers of individual charges (ensemble) are involved. As device geometries
      become very small, the ensemble "averaging" becomes far less accurate. In this
      work, the charge-capture/emission dynamic of Metal-Oxide-Semiconductor-Field
      Effect-Transistor (MOSFET) is re-examined with full consideration of individual
      charges and the local field in their immediate vicinity. A dramatic modification
      of the local band diagram resulted, forcing a drastic change in emission
      mechanism. The implication is that many well-understood phenomena involving
      charge capture/emission will need to be reconsidered. As an example, this new
      picture is applied to the random telegraph noise (RTN) phenomenon. When the
      screening of a trapped charge by a polar medium such as SiO2 is quantitatively
      accounted for in this local field picture, a new physically sound RTN emission
      mechanism emerges. Similarly, the dynamics of post-stress recovery of Negative
      Bias-Instability of p-channel MOSFET can be more rationally explained.

PMID- 29375149
TI  - Smoking Decreases Endometrial Thickness in IVF/ICSI Patients.
AB  - Introduction: Smoking is a serious problem for the health care system. Many of
      the compounds identified in cigarette smoke have toxic effects on the fertility
      of both females and males. The purpose of this study was to determine whether
      smoking affects clinical factors during IVF/ICSI therapy in a single-center
      reproductive unit. Material and Methods: In a retrospective study of 200 IVF/ICSI
      cycles, endometrial thickness and the outcome of IVF/ICSI therapy were analyzed.
      Results: Endometrial thickness was significantly lower in smoking patients than
      in non-smoking patients (10.4 +/- 1.5 mm vs. 11.6 +/- 1.8 mm). Age was
      significantly higher in women who failed to conceive. The total dose of
      gonadotropins administered was significantly lower in pregnant patients and the
      highest pregnancy rate was achieved with an rFSH protocol. BMI and number of
      cigarettes smoked did not influence treatment outcomes in this study. Conclusion:
      We showed that smoking has a negative effect on endometrial thickness on the day
      of embryo transfer. This may help to further explain the detrimental influence of
      tobacco smoke on implantation and pregnancy rates during assisted reproduction
      therapy.

PMID- 29375151
TI  - Compression for Quadratic Similarity Queries.
AB  - The problem of performing similarity queries on compressed data is considered. We
      focus on the quadratic similarity measure, and study the fundamental tradeoff
      between compression rate, sequence length, and reliability of queries performed
      on the compressed data. For a Gaussian source, we show that the queries can be
      answered reliably if and only if the compression rate exceeds a given threshold
      the identification rate- which we explicitly characterize. Moreover, when
      compression is performed at a rate greater than the identification rate,
      responses to queries on the compressed data can be made exponentially reliable.
      We give a complete characterization of this exponent, which is analogous to the
      error and excess-distortion exponents in channel and source coding, respectively.
      For a general source, we prove that, as with classical compression, the Gaussian
      source requires the largest compression rate among sources with a given variance.
      Moreover, a robust scheme is described that attains this maximal rate for any
      source distribution.

PMID- 29375152
TI  - Minimax Estimation of Functionals of Discrete Distributions.
AB  - We propose a general methodology for the construction and analysis of essentially
      minimax estimators for a wide class of functionals of finite dimensional
      parameters, and elaborate on the case of discrete distributions, where the
      support size S is unknown and may be comparable with or even much larger than the
      number of observations n. We treat the respective regions where the functional is
      nonsmooth and smooth separately. In the nonsmooth regime, we apply an unbiased
      estimator for the best polynomial approximation of the functional whereas, in the
      smooth regime, we apply a bias-corrected version of the maximum likelihood
      estimator (MLE). We illustrate the merit of this approach by thoroughly analyzing
      the performance of the resulting schemes for estimating two important information
      measures: 1) the entropy [Formula: see text] and 2) [Formula: see text], alpha >
      0. We obtain the minimax L2 rates for estimating these functionals. In
      particular, we demonstrate that our estimator achieves the optimal sample
      complexity n ? S/ln S for entropy estimation. We also demonstrate that the sample
      complexity for estimating Falpha (P), 0 < alpha < 1, is n ? S1/alpha /ln S, which
      can be achieved by our estimator but not the MLE. For 1 < alpha < 3/2, we show
      the minimax L2 rate for estimating Falpha (P) is (n ln n)-2(alpha-1) for infinite
      support size, while the maximum L2 rate for the MLE is n-2(alpha-1). For all the
      above cases, the behavior of the minimax rate-optimal estimators with n samples
      is essentially that of the MLE (plug-in rule) with n ln n samples, which we term
      "effective sample size enlargement." We highlight the practical advantages of our
      schemes for the estimation of entropy and mutual information. We compare our
      performance with various existing approaches, and demonstrate that our approach
      reduces running time and boosts the accuracy. Moreover, we show that the minimax
      rate-optimal mutual information estimator yielded by our framework leads to
      significant performance boosts over the Chow-Liu algorithm in learning graphical
      models. The wide use of information measure estimation suggests that the insights
      and estimators obtained in this paper could be broadly applicable.

PMID- 29375153
TI  - Network Compression: Worst Case Analysis.
AB  - We study the problem of communicating a distributed correlated memoryless source
      over a memoryless network, from source nodes to destination nodes, under
      quadratic distortion constraints. We establish the following two complementary
      results: 1) for an arbitrary memoryless network, among all distributed memoryless
      sources of a given correlation, Gaussian sources are least compressible, that is,
      they admit the smallest set of achievable distortion tuples and 2) for any
      memoryless source to be communicated over a memoryless additive-noise network,
      among all noise processes of a given correlation, Gaussian noise admits the
      smallest achievable set of distortion tuples. We establish these results
      constructively by showing how schemes for the corresponding Gaussian problems can
      be applied to achieve similar performance for (source or noise) distributions
      that are not necessarily Gaussian but have the same covariance.

PMID- 29375154
TI  - Rateless Lossy Compression via the Extremes.
AB  - We begin by presenting a simple lossy compressor operating at near-zero rate: The
      encoder merely describes the indices of the few maximal source components, while
      the decoder's reconstruction is a natural estimate of the source components based
      on this information. This scheme turns out to be near optimal for the memoryless
      Gaussian source in the sense of achieving the zero-rate slope of its distortion
      rate function. Motivated by this finding, we then propose a scheme comprised of
      iterating the above lossy compressor on an appropriately transformed version of
      the difference between the source and its reconstruction from the previous
      iteration. The proposed scheme achieves the rate distortion function of the
      Gaussian memoryless source (under squared error distortion) when employed on any
      finite-variance ergodic source. It further possesses desirable properties, and
      we, respectively, refer to as infinitesimal successive refinability,
      ratelessness, and complete separability. Its storage and computation requirements
      are of order no more than (n2)/(log beta n) per source symbol for beta > 0 at
      both the encoder and the decoder. Though the details of its derivation,
      construction, and analysis differ considerably, we discuss similarities between
      the proposed scheme and the recently introduced Sparse Regression Codes of
      Venkataramanan et al.

PMID- 29375155
TI  - Design and Development of a New Multi-Projection X-Ray System for Chest Imaging.
AB  - Overlapping anatomical structures may confound the detection of abnormal
      pathology, including lung nodules, in conventional single-projection chest
      radiography. To minimize this fundamental limiting factor, a dedicated digital
      multi-projection system for chest imaging was recently developed at the Radiology
      Department of Duke University. We are reporting the design of the multi
      projection imaging system and its initial performance in an ongoing clinical
      trial. The system is capable of acquiring multiple full-field projections of the
      same patient along both the horizontal and vertical axes at variable speeds and
      acquisition frame rates. These images acquired in rapid succession from slightly
      different angles about the posterior-anterior (PA) orientation can be correlated
      to minimize the influence of overlying anatomy. The developed system has been
      tested for repeatability and motion blur artifacts to investigate its robustness
      for clinical trials. Excellent geometrical consistency was found in the tube
      motion, with positional errors for clinical settings within 1%. The effect of
      tube-motion on the image quality measured in terms of impact on the Modulation
      Transfer Function (MTF) was found to be minimal. The system was deemed clinic
      ready and a clinical trial was subsequently launched. The flexibility of image
      acquisition built into the system provides a unique opportunity to easily modify
      it for different clinical applications, including tomosynthesis, correlation
      imaging (CI), and stereoscopic imaging.

PMID- 29375156
TI  - Reduced resistance drift in tunnel junctions using confined tunnel barriers.
AB  - Metal-insulator-metal (MIM) tunnel junctions with the aluminum oxide tunnel
      barriers confined between cobalt electrodes exhibit less resistance drift over
      time than junctions that utilize a thick, unconfined aluminum electrode. The
      improved long time stability is attributed to better initial oxide quality
      achieved through confinement (use of a potential energy well for the oxygen) and
      plasma oxidation. In this work, Co/AlOx/Co and Co/Al/AlOx/Co tunnel junction
      aging is compared over a period of approximately 9 months using transport
      measurements and Wentzel-Kramers-Brillouin (WKB) based modelling. The Co/AlOx/Co
      (confined) tunnel junction resistance increased by (32 +/- 6) % over 5400 h,
      while Co/Al/AlOx/Co (unconfined) tunnel junction resistance increased by (85 +/-
      23) % over 5200 h. Fit parameters for the tunnel barrier width and potential
      energy barriers were extracted using WKB transport modelling. These values change
      only a small amount in the confined Co/AlOx/Co tunnel junction but show a
      significant drift in the unconfined Co/AlOx/Co tunnel junction.

PMID- 29375157
TI  - Divergent Pathways to Assimilation? Local Marriage Markets and Intermarriage
      among U.S. Hispanics.
AB  - The growing diversity of the U.S. population raises questions about integration
      among America's fastest growing minority population-Hispanics. The canonical view
      is that intermarriage with the native-born white population represents a singular
      pathway to assimilation, one that varies over geographic space in response to
      uneven local marital opportunities. Using data on past-year marriage from the
      2009-2014 American Community Survey, we demonstrate high rates of intermarriage
      among Hispanics. Our analyses identify whether Hispanics marry co-ethnics, non-co
      ethnic Hispanics, non-Hispanic whites, non-Hispanic blacks, or other minorities.
      We highlight variation by race, nativity, and socioeconomic status, but also
      reveal that Hispanics living in new immigrant destinations are more likely to
      intermarry than those living in traditional Hispanic gateways. Indeed, the higher
      out-marriage in new destinations disappears when the demographic context of
      reception is taken into account. Our analysis underscores that patterns of
      marital assimilation among Hispanics are neither monolithic nor expressed
      uniformly across geographic space.

PMID- 29375158
TI  - Workflows and Provenance: Toward Information Science Solutions for the Natural
      Sciences.
AB  - The era of big data and ubiquitous computation has brought with it concerns about
      ensuring reproducibility in this new research environment. It is easy to assume
      computational methods self-document by their very nature of being exact,
      deterministic processes. However, similar to laboratory experiments, ensuring
      reproducibility in the computational realm requires the documentation of both the
      protocols used (workflows) as well as a detailed description of the computational
      environment: algorithms, implementations, software environments as well as the
      data ingested and execution logs of the computation. These two aspects of
      computational reproducibility (workflows and execution details) are discussed in
      the context of biomolecular Nuclear Magnetic Resonance spectroscopy (bioNMR) as
      well as the PRIMAD model for computational reproducibility.

PMID- 29375159
TI  - Discrete maximal regularity of time-stepping schemes for fractional evolution
      equations.
AB  - In this work, we establish the maximal [Formula: see text]-regularity for several
      time stepping schemes for a fractional evolution model, which involves a
      fractional derivative of order [Formula: see text], [Formula: see text], in time.
      These schemes include convolution quadratures generated by backward Euler method
      and second-order backward difference formula, the L1 scheme, explicit Euler
      method and a fractional variant of the Crank-Nicolson method. The main tools for
      the analysis include operator-valued Fourier multiplier theorem due to Weis (Math
      Ann 319:735-758, 2001. doi:10.1007/PL00004457) and its discrete analogue due to
      Blunck (Stud Math 146:157-176, 2001. doi:10.4064/sm146-2-3). These results
      generalize the corresponding results for parabolic problems.

PMID- 29375160
TI  - Multiscale techniques for parabolic equations.
AB  - We use the local orthogonal decomposition technique introduced in Malqvist and
      Peterseim (Math Comput 83(290):2583-2603, 2014) to derive a generalized finite
      element method for linear and semilinear parabolic equations with spatial
      multiscale coefficients. We consider nonsmooth initial data and a backward Euler
      scheme for the temporal discretization. Optimal order convergence rate, depending
      only on the contrast, but not on the variations of the coefficients, is proven in
      the [Formula: see text]-norm. We present numerical examples, which confirm our
      theoretical findings.

PMID- 29375161
TI  - Convergence of the Euler-Maruyama method for multidimensional SDEs with
      discontinuous drift and degenerate diffusion coefficient.
AB  - We prove strong convergence of order [Formula: see text] for arbitrarily small
      [Formula: see text] of the Euler-Maruyama method for multidimensional stochastic
      differential equations (SDEs) with discontinuous drift and degenerate diffusion
      coefficient. The proof is based on estimating the difference between the Euler
      Maruyama scheme and another numerical method, which is constructed by applying
      the Euler-Maruyama scheme to a transformation of the SDE we aim to solve.

PMID- 29375162
TI  - Rediscovery of the species of 'ancestral Volvox': morphology and phylogenetic
      position of Pleodorina sphaerica (Volvocales, Chlorophyceae) from Thailand.
AB  - Pleodorina sphaerica Iyengar was considered to be a phylogenetic link between
      Volvox and the type species Pleodorina californica Shaw because it has small
      somatic cells distributed from the anterior to posterior poles in 64- or 128
      celled vegetative colonies. However, cultural studies and molecular and
      ultrastructural data are lacking in P. sphaerica, and this species has not been
      recorded since 1951. Here, we performed light and electron microscopy and
      molecular phylogeny of P. sphaerica based on newly established culture strains
      originating from Thailand. Morphological features of the present Thai species
      agreed well with those of the previous studies of the Indian material of P.
      sphaerica and with those of the current concept of the advanced members of the
      Volvocaceae. The present P. sphaerica strains exhibited homothallic sexuality;
      male and facultative female colonies developed within a single clonal culture.
      Chloroplast multigene phylogeny demonstrated that P. sphaerica was sister to two
      other species of Pleodorina (P. californica and Pleodorina japonica Nozaki)
      without posterior somatic cells, and these three species of Pleodorina formed a
      robust clade, which was positioned distally in the large monophyletic group
      including nine taxa of Volvox sect. Merrillosphaera and Volvox (sect.
      Janetosphaera) aureus Ehrenberg. Based on the present phylogenetic results,
      evolutionary losses of posterior somatic cells might have occurred in the
      ancestor of P. californica and P. japonica. Thus, P. sphaerica might represent an
      ancestral morphology of Pleodorina, rather than of Volvox.

PMID- 29375163
TI  - A Field Experiment on Search Costs and the Formation of Scientific
      Collaborations.
AB  - We present the results of a field experiment conducted at Harvard Medical School
      to understand the extent to which search costs affect matching among scientific
      collaborators. We generated exogenous variation in search costs for pairs of
      potential collaborators by randomly assigning individuals to 90-minute structured
      information-sharing sessions as part of a grant funding opportunity. We estimate
      that the treatment increases the probability of grant co-application of a given
      pair of researchers by 75%. The findings suggest that matching between scientists
      is subject to considerable frictions, even in the case of geographically
      proximate scientists working in the same institutional context.

PMID- 29375164
TI  - [Ageing, health and economics. National inquest into health and ageing in
      Mexico].
AB  - Mexico is experiencing a demographic transition in which the percentage of the
      population older than 50 years of age is growing rapidly as a result of increases
      in life expectancy. This population has special needs that must be taken into
      account when formulating policy, especially in terms of access to health care
      services and social security. In this article we present a general description of
      the Mexican Health and Aging Survey (MHAS), a panel study that began in 2001 and
      that provides a unique opportunity to study complex demographic and economic
      issues through the exploration of personal characteristics, socioeconomic
      transfers and health indicators for a sample of 15 186 middle and older age
      adults. We also present the most important results from different studies that
      have used MHAS up to date. Our review shows that Mexico faces substantial
      challenges in order to be able to satisfy the demand for health services for a
      population that is being increasingly threatened by chronic disease, particularly
      the elderly population that lacks health insurance coverage.

PMID- 29375165
TI  - "I Used to Be Wild": Adolescent Perspectives on the Influence of Family, Peers,
      School, and Neighborhood on Positive Behavioral Transition.
AB  - Public health practice involving adolescents is largely focused on preventing or
      delaying the initiation of risk behavior. However, given the experimental and
      exploratory nature of this developmental period, this is often impractical. This
      paper focuses on behavioral transitions and the ways in which youth involved in
      risk behaviors shift to more promotive behaviors. Based on a positive youth
      development perspective, in-depth interviews with urban youth were conducted and
      analyzed to gain an understanding of the influences on behavior change. Specific
      family support, ability to detach from harmful peer relationships, and school
      connectedness and vocational support emerged as important to those youths who
      made a positive behavioral transition. These findings suggest the importance of
      understanding ways to support the cessation of involvement in risk behaviors and
      reinforce the significance of contextual influences on youth development.

PMID- 29375166
TI  - Kin in Daily Routines: Time Use and Childrearing in Rural South Africa.

PMID- 29375167
TI  - Generalizing the Network Scale-Up Method: A New Estimator for the Size of Hidden
      Populations.
AB  - The network scale-up method enables researchers to estimate the size of hidden
      populations, such as drug injectors and sex workers, using sampled social network
      data. The basic scale-up estimator offers advantages over other size estimation
      techniques, but it depends on problematic modeling assumptions. We propose a new
      generalized scale-up estimator that can be used in settings with non-random
      social mixing and imperfect awareness about membership in the hidden population.
      Further, the new estimator can be used when data are collected via complex sample
      designs and from incomplete sampling frames. However, the generalized scale-up
      estimator also requires data from two samples: one from the frame population and
      one from the hidden population. In some situations these data from the hidden
      population can be collected by adding a small number of questions to already
      planned studies. For other situations, we develop interpretable adjustment
      factors that can be applied to the basic scale-up estimator. We conclude with
      practical recommendations for the design and analysis of future studies.

PMID- 29375168
TI  - Effects of concurrent task demands on language planning in fluent children and
      adults.
AB  - Purpose: The aim of the present study was to investigate how children and adults
      allocate cognitive resources to performing segmental encoding and monitoring in a
      dual task paradigm and the response patterns of the primary and secondary tasks
      in the dual task. Methods: Participants were 20 children divided equally into two
      age groups-7 to 11 years, 12 to 15 years, and 10 adults. The primary task
      required participants to monitor phonemic segments in a picture - written word
      interference paradigm while silently naming the pictures. The picture and
      distractor word were the same (replica), related (phoneme onset overlap), or
      unrelated. The secondary task required participants to make pitch judgments on
      tones presented at short (330 ms) or long (1130 ms) stimulus onset asynchrony
      (SOA) from picture onset. Results: Developmental differences were observed in
      both response times and percent errors in the primary and secondary tasks. Slower
      responses to the primary task were evident at the long SOA, related condition.
      Slower response times to the tone decision task were evident at the short than
      the long SOA. The findings support the capacity sharing account of dual task
      performance and suggest that dual task costs during language planning are higher
      in children than adults.

PMID- 29375169
TI  - Sparse simultaneous signal detection for identifying genetically controlled
      disease genes.
AB  - Genome-wide association studies (GWAS) and differential expression analyses have
      had limited success in finding genes that cause complex diseases such as heart
      failure (HF), a leading cause of death in the United States. This paper proposes
      a new statistical approach that integrates GWAS and expression quantitative trait
      loci (eQTL) data to identify important HF genes. For such genes, genetic
      variations that perturb its expression are also likely to influence disease risk.
      The proposed method thus tests for the presence of simultaneous signals: SNPs
      that are associated with the gene's expression as well as with disease. An
      analytic expression for the p-value is obtained, and the method is shown to be
      asymptotically adaptively optimal under certain conditions. It also allows the
      GWAS and eQTL data to be collected from different groups of subjects, enabling
      investigators to integrate public resources with their own data. Simulation
      experiments show that it can be more powerful than standard approaches and also
      robust to linkage disequilibrium between variants. The method is applied to an
      extensive analysis of HF genomics and identifies several genes with biological
      evidence for being functionally relevant in the etiology of HF. It is implemented
      in the R package ssa.

PMID- 29375170
TI  - Effect of Green Macroalgal Blooms on the Behavior, Growth, and Survival of
      Cockles (Clinocardium nuttallii) in Pacific NW Estuaries.
AB  - Nutrient over-enrichment can produce adverse ecological effects within coastal
      ecosystems and negatively impact the production of ecosystem goods and services.
      In small estuaries of the U.S. Pacific Northwest, seasonal blooms of green
      macroalgae (GMA; Family Ulvaceae) are primarily associated with natural nutrient
      input, rather than anthropogenic sources. This provided us a unique opportunity
      to investigate the effects of naturally-stimulated macroalgal blooms on
      intertidal bivalves. Clinocardium nuttallii (heart cockles) are an important
      species for shellfisheries in the region. In summer population surveys, we found
      that cockles emerged from the sediment with greater frequency as GMA biomass
      increased. Experimental manipulation of GMA biomass in the field showed that GMA
      elicited emergence, evoked above-ground lateral movement, inhibited shell growth,
      and increased mortality (by 34.0 +/- 15.2%) in cockles. Laboratory experiments
      revealed that the interaction of a weighted barrier at the sediment surface and
      GMA presence elicited rapid emergence among cockles. Risk assessment of the
      emergence response in cockles showed that the in situ emergent population
      experienced 11.0 +/- 8.0% mortality due to gull predation, while laboratory
      exposure to elevated temperatures (>=34  degrees C) slowed valve-closure,
      inhibited reburial, and increased mortality, which could have translated to 7.1
      +/- 1.5% in situ mortality. We found that cockles avoided mortality due to burial
      below GMA mats by emerging from the sediment, but that behavior consequently put
      them at risk of mortality due to heat stress or gull predation. Regardless of
      nutrient source, our research showed that GMA blooms pose a threat to the
      survival of intertidal bivalves.

PMID- 29375171
TI  - Labor Force Participation of Mexican Elderly: the Importance of Health.
AB  - Se analizan los factores determinantes de la participacion en la fuerza de
      trabajo de la poblacion mexicana de 50 anos o mas, con datos de la Encuesta
      nacional sobre salud y envejecimiento en Mexico, ENASEM. Se estudio en particular
      la importancia de la salud en la decision sobre la participacion, tomando en
      cuenta la endogeneidad potencial de la salud. Los resultados indican que una
      mejor salud causa un mayor apego al mercado laboral. No se encontro evidencia
      clara de que el empleo afecte la salud, pero no puede descartarse que los efectos
      de las malas condiciones laborales y la justificacion se eliminen mutuamente.
      Existen indicadores de que la autoevaluacion de la salud no captura todos los
      aspectos relevantes de la salud. En la toma de decisiones para establecer
      politicas, la importancia directa de las circunstancias financieras podria ser
      mas relevante que el papel de la salud. The determinants of the labor force
      participation of people in Mexico aged 50 and over are analyzed using data of the
      Mexican Health and Aging Study (MHAS). In particular we study the importance of
      health in the participation decision, taking into account the potential
      endogeneity of health. The results indicate that a better health causes a
      stronger attachment to the labor market. We find no clear evidence that
      employment affects health, but it cannot be ruled out that the effects of bad
      labor circumstances and justification eliminate each other. There are indications
      that self-assessed health does not capture all relevant aspects of health. For
      policy decisions the direct importance of financial circumstances could be more
      relevant than the role of health.

PMID- 29375172
TI  - Wealth in Middle and Old Age in Mexico: The Role of International Migration.
AB  - This article examines the impact that past migration to the U.S. has on the
      current economic well-being of individuals in middle or old age who have returned
      to Mexico. A priori, the net effect of U.S. migration on wealth among return
      migrants is difficult to predict; there are counteracting factors that can affect
      wealth positively or negatively. Using data from the Mexican Health and Aging
      Study 2001 and correcting for selection factors, the long-term effect of U.S.
      migration for return migrants was found consistently positive in terms of their
      accumulated personal wealth at middle and old age. This article speculates about
      the possible mechanisms that can explain this apparent advantage.

PMID- 29375173
TI  - INTEGRATING HEALTH INTO BUILDINGS OF THE FUTURE.
AB  - The health and wellbeing of building occupants should be a key priority in the
      design, building, and operation of new and existing buildings. Buildings can be
      designed, renovated, and constructed to promote healthy environments and
      behaviors and mitigate adverse health outcomes. This paper highlights health in
      terms of the relationship between occupants and buildings, as well as the
      relationship of buildings to the community. In the context of larger systems,
      smart buildings and green infrastructure strategies serve to support public
      health goals. At the level of the individual building, interventions that promote
      health can also enhance indoor environmental quality and provide opportunities
      for physical activity. Navigating the various programs that use metrics to
      measure a building's health impacts reveals that there are multiple co-benefits
      of a "healthy building," including those related to the economy, environment,
      society, transportation, planning, and energy efficiency.

PMID- 29375174
TI  - A Bayesian finite mixture change-point model for assessing the risk of novice
      teenage drivers.
AB  - The driving risk during the initial period after licensure for novice teenage
      drivers is typically the highest but decreases rapidly right after. The change
      point of driving risk is a critical parameter for evaluating teenage driving
      risk, which also varies substantially among drivers. This paper presents latent
      class recurrent-event change-point models for detecting the change-points. The
      proposed model is applied to the Naturalist Teenage Driving Study, which
      continuously recorded the driving data of 42 novice teenage drivers for 18 months
      using advanced in-vehicle instrumentation. We propose a hierarchical BFMM to
      estimate the change-points by clusters of drivers with similar risk profiles. The
      model is based on a non-homogeneous Poisson process with piecewise-constant
      intensity functions. Latent variables which identify the membership of the
      subjects are used to detect potential clusters among subjects. Application to the
      Naturalistic Teenage Driving Study identifies three distinct clusters with change
      points at 52.30, 108.99 and 150.20 hours of driving after first licensure,
      respectively. The overall intensity rate and the pattern of change also differ
      substantially among clusters. The results of this research provide more insight
      in teenagers' driving behaviour and will be critical to improve young drivers'
      safety education and parent management programs, as well as provide crucial
      reference for the GDL regulations to encourage safer driving.

PMID- 29375175
TI  - The Effect of Vietnam-Era Conscription and Genetic Potential for Educational
      Attainment on Schooling Outcomes.
AB  - This study examines whether draft lottery estimates of the causal effects of
      Vietnam-era military service on schooling vary by an individual's genetic
      propensity toward educational attainment. To capture the complex genetic
      architecture that underlies the bio-developmental pathways, behavioral traits and
      evoked environments associated with educational attainment, we construct
      polygenic scores (PGS) for respondents in the Health and Retirement Study (HRS)
      that aggregate thousands of individual loci across the human genome and weight
      them by effect sizes derived from a recent genome-wide association study (GWAS)
      of years of education. Our findings suggest veterans with below average PGSs for
      educational attainment may have completed fewer years of schooling than
      comparable non-veterans. On the other hand, we do not find any difference in the
      educational attainment of veterans and non-veterans with above average PGSs.
      Results indicate that public policies and exogenous environments may induce
      heterogeneous treatment effects by genetic disposition.

PMID- 29375176
TI  - Increased Cathepsin D Correlates with Clinical Parameters in Newly Diagnosed Type
      2 Diabetes.
AB  - Background: Cathepsin D has been recently implicated in insulin resistance and
      cardiovascular disease. This study was designed to investigate the relationship
      between cathepsin D and newly diagnosed type 2 diabetes. Methods: Circulating
      cathepsin D levels and metabolic variables were measured in 98 cases and 98
      controls. Myocardial performance index "Tei index" that reflects both left
      ventricular systolic and diastolic function was measured with Doppler
      echocardiography in cases. Results: Newly diagnosed type 2 diabetes demonstrated
      significantly higher circulating cathepsin D concentrations than controls (median
      level: 227 ng/ml versus 174 ng/ml, P < 0.01). In newly diagnosed type 2 diabetes,
      a significant correlation was found between cathepsin D levels and HOMA-IR
      (homeostatic model assessment of insulin resistance) (r = 0.25, P = 0.01). In
      contrast, no significant correlation was found between cathepsin D levels and
      clinical parameters in the control group (all P > 0.05). Interestingly,
      correlation analysis revealed a positive association between cathepsin D levels
      and Tei index in type 2 diabetes (r = 0.22, P = 0.03). Conclusions: Increased
      levels of circulating cathepsin D are closely linked with the presence of type 2
      diabetes, and cathepsin D might serve as a novel biomarker for cardiac
      dysfunction in newly diagnosed type 2 diabetes.

PMID- 29375178
TI  - The piloting of a culturally centered American Indian family prevention program:
      a CBPR partnership between Mescalero Apache and the University of New Mexico.
AB  - The Mescalero Apache Family Listening Program (MAFLP) is a culturally centered
      family prevention program with third, fourth, and fifth graders; a
      parent/caregiver; and a family elder. The program follows a positive youth
      development model to develop stronger communication and shared cultural practices
      between elders, parents, and youth in the tribe to reduce substance initiation of
      use among the youth. The MAFLP was created using a community-based participatory
      research (CBPR) approach in partnership with the University of New Mexico. The
      research focus of MAFLP is centered on the adaptation of a family curriculum from
      a Navajo and Pueblo version of the Family Listening Program to an Apache version,
      the establishment of a (Apache) Tribal Research Team, and the piloting of the
      curriculum with Apache families. MAFLP was piloted twice, and evaluation measures
      were collected focused on formative and impact evaluation. This article provides
      a background on Mescalero Apache then introduces the Navajo and Pueblo version of
      a Family Listening and Family Circle Program, respectively, next, the CBPR
      research partnership between Mescalero Apache and the University of New Mexico
      and the creation of a Mescalero Apache Tribal Research Team followed by the
      development and adaptation of a Mescalero Apache Family Listening Program
      including implementation and evaluation, and concluding with preliminary
      findings.

PMID- 29375179
TI  - [Mexico and the State of Guanajuato: Intergenerational transfers to the elderly].
AB  - In Mexico, there is a range of formal and informal transfers to help older
      adults. This paper analyses national trends and the results of a study focused on
      the federal entity of Guanajuato. The distribution of the support provided
      confirms that the transfers made by the social security system have an urban bias
      and that formal transfers from the federal government are oriented to the least
      urban areas, and especially rural areas. Despite the existence of formal
      transfers (which are irregular and insufficient), the economic and health needs
      of older adults remain unmet and, as a result, their relatives make informal
      transfers. In Mexico, and more specifically in Guanajuato, those who live with
      older adults provide a very significant amount of support, whereas those who have
      migrated do not. On the basis of this material, we analyse of the role played by
      descendants, according to their cohort and migration status. In any case, it is
      clear that there the dynamics of intergenerational transfers are different in
      each national entity.

PMID- 29375177
TI  - Identification of Circulating Long Noncoding RNA Linc00152 as a Novel Biomarker
      for Diagnosis and Monitoring of Non-Small-Cell Lung Cancer.
AB  - Objective: Long noncoding RNAs (lncRNAs) have been reported to play vital roles
      in non-small-cell lung cancer (NSCLC). Recently, long noncoding RNA Linc00152 has
      been reported to play important roles in various cancers. In this study, our aim
      was to investigate its expression pattern and clinical significance and further
      evaluate its diagnostic value for NSCLC. Methods: The levels of Linc00152 were
      detected in NSCLC tissues and plasma samples by quantitative real-time PCR (qRT
      PCR). Receiver operating characteristic (ROC) curves were depicted to evaluate
      the diagnostic value. Results: We found that Linc00152 levels were upregulated in
      both NSCLC tissues and plasma samples. Plasma Linc00152 levels were significantly
      lower in postoperative samples than in preoperative samples. Besides, high
      Linc00152 expression was significantly correlated with tumor size (r = 0.293, P =
      0.005) and tumor stage (r = 0.324, P = 0.011). The ROC curves indicated that
      plasma Linc00152 has high diagnostic accuracy for NSCLC, and the area under curve
      (AUC) for NSCLC versus healthy was 0.816 (95% CI: 0.757-0.875). Moreover, we
      found that the combination of Linc00152 and CEA could provide a more powerful
      diagnosis efficiency than Linc00152 or CEA alone (AUC = 0.881, 95% CI: 0.836
      0.926). Conclusions: Plasma Linc00152 could serve as a promising biomarker for
      diagnosing and monitoring NSCLC.

PMID- 29375181
TI  - Product familiarisation programs.

PMID- 29375180
TI  - Designing a food tax to impact food-related non-communicable diseases: the case
      of Chile.
AB  - The global shift towards diets high in sugar-sweetened beverages (SSBs) and
      energy dense ultra-processed foods is linked to higher prevalence of obesity,
      diabetes and most other noncommunicable diseases (NCDs), causing significant
      health costs. Chile has the highest SSB consumption in the world, very high junk
      food intake and very rapid increases in these poor components of the diet plus
      obesity prevalence. This study's purpose is to compare the effect of different
      tax schemes for SSBs and ultra-processed foods on nutrient availability,
      utilizing price-elasticities, which are estimated from a Quadratic Almost Ideal
      Demand System model, using the 2011-2012 Income and Expenditure survey. We take
      into account the high proportion of households not purchasing various food and
      beverage groups (censored nature of data). The food groups considered were:
      sweets and desserts; salty snacks and chips; meat products and fats; fruits,
      vegetables and seafood; cereals and cereal products; SSB ready-to-drink; SSB from
      concentrate; plain water, coffee and tea; and milk, which together represent 90%
      of food expenditures. The simulated taxes were: (1) 40% price tax on SSBs(22%
      above the current tax level); (2) a 5 cents per gram of sugar tax on products
      with added sugar; and (3) 30% price tax on all foods(27% above current tax
      levels) and beverages (12% above the current tax level) exceeding thresholds on
      sodium, saturated fat, and added sugar and for which marketing is restricted
      (based on a Chilean law, effective June 16 2016). Unhealthy foods are price
      elastic (-1.99 for salty snacks and chips, -1.06 for SSBs ready-to-drink, and 
      1.27 for SSBs from concentrate), meaning that the change in consumption is
      proportionally larger with respect to a change in price. Results are robust to
      different model specification, and consistent among different socioeconomic sub
      populations. Overall, the tax on marketing controlled foods and beverages is
      associated with the largest reduction in household purchases of sodium, added
      sugar, saturated fat and calorie purchases. Chile is unique in currently having
      instituted a small current SSB tax as well as marketing controls and front-of
      package labeling of unhealthy foods and beverages. The design of a larger, more
      comprehensive tax to enhance the overall effect of these policies on healthier
      diets is a next critical step. This study shows that a large tax on the same
      foods and beverages already delineated as unhealthy by the marketing controls and
      front-of-pack labeling should prove to be more effective for promoting a
      healthier diet.

PMID- 29375182
TI  - Functional dyspepsia.

PMID- 29375183
TI  - Thyroid disorders in pregnancy and postpartum.

PMID- 29375184
TI  - Hyperprolactinaemia.

PMID- 29375186
TI  - Top 10 drugs 2016-17.

PMID- 29375185
TI  - Clozapine in primary care.

PMID- 29375187
TI  - Medicines Australia Code of Conduct: breaches 2016-17.

PMID- 29375188
TI  - Daratumumab.

PMID- 29375189
TI  - Lenvatinib.

PMID- 29375190
TI  - Milnacipran hydrochloride.

PMID- 29375191
TI  - Nepafenac.

PMID- 29375192
TI  - Older Former Prisoners' Pathways to Sobriety.
AB  - This study explores how older age shapes processes of substance abuse cessation
      among male substance users recently released from prison. Semi-structured in
      depth interviews and brief surveys were conducted with 15 men aged 49+, released
      from prison in a large, Eastern U.S. city. A follow-up interview was conducted
      with each participant (n=15). Conventional content analysis was used to analyze
      these data. Aging was central to the stories men told about attaining and
      maintaining sobriety. Men gained clarity after forced detoxification in prison,
      which was often followed by a period of reflection and evaluation of their lives.
      Older age seemed integral for this period of sobriety and reflection to catalyze
      cognitive change, a phenomenon I term Sober Aged Reflection. Further, men
      described a heightened awareness of mortality that had come with older age, and
      were deeply afraid of dying in prison. This fear helped inspire a new commitment
      to sobriety and concordant rejection of the crime that had been linked with their
      drug use in the past. Finally, men revealed identities and goals that had changed
      with time, changes incompatible with on-going drug use. Policy implications are
      discussed.

PMID- 29375193
TI  - Predator recognition and differential behavioural responses of adult wood
      warblers Phylloscopus sibilatrix.
AB  - Birds often engage in nest defence against predators to improve breeding success,
      but defence efficiency requires the capability to assess the threat level posed
      by potential predators. For species with low breeding-site tenacity, which may
      encounter varying occurrence and density of predators in different areas, threat
      recognition could be compromised due to naivety, and so predator recognition may
      focus on broad key features to diminish the risk of misidentification. We
      experimentally tested this hypothesis by recording behavioural reactions of the
      nomadic wood warbler Phylloscopus sibilatrix to objects reflecting various levels
      of threat: least weasel and Eurasian jay taxidermy mounts, an inanimate object
      and an empty display mount. To assess actual nest predators, we used remote
      cameras to record predation events at wood warbler nests. As in other studies in
      Western Europe, Eurasian jay was found to be the main nest predator, with
      occasional predation by least weasel. The reaction of adult warblers to the
      models was generally to remain silent and on nests during the incubation stage
      presumably due to the need to maintain efficient nest camouflage and concealment.
      During the nestling stage, behavioural responses of adult warblers, calling and
      suspended feeding of young, showed the strongest effects from the jay taxidermy
      mount, moderate to the weasel and weakest to the inanimate object and empty
      mount. As the reaction of wood warblers reflected the degree of genuine threat
      posed by the predators depicted by the models, we conclude that predator
      recognition may be present in this species.

PMID- 29375194
TI  - Differences in safety training among smaller and larger construction firms with
      non-native workers: Evidence of overlapping vulnerabilities.
AB  - Collaborative efforts between the National Institute for Occupational Safety and
      Health (NIOSH) and the American Society of Safety Engineers (ASSE) led to a
      report focusing on overlapping occupational vulnerabilities, specifically small
      construction businesses employing young, non-native workers. Following the
      report, an online survey was conducted by ASSE with construction business
      representatives focusing on training experiences of non-native workers. Results
      were grouped by business size (50 or fewer employees or more than 50 employees).
      Smaller businesses were less likely to employ a supervisor who speaks the same
      language as immigrant workers (p < .001). Non-native workers in small businesses
      received fewer hours of both initial safety training (p = .005) and monthly
      ongoing safety training (p = .042). Immigrant workers in smaller businesses were
      less likely to receive every type of safety training identified in the survey
      (including pre-work safety orientation [p < .001], job-specific training [p <
      .001], OSHA 10-hour training [p = .001], and federal/state required training [p <
      .001]). The results highlight some of the challenges a vulnerable worker
      population faces in a small business, and can be used to better focus
      intervention efforts. Among businesses represented in this sample, there are
      deflcits in the amount, frequency, and format of workplace safety and health
      training provided to non-native workers in smaller construction businesses
      compared to those in larger businesses. The types of training conducted for non
      native workers in small business were less likely to take into account the
      language and literacy issues faced by these workers. The findings suggest the
      need for a targeted approach in providing occupational safety and health training
      to non-native workers employed by smaller construction businesses.

PMID- 29375195
TI  - Staying cool in a changing climate: Reaching vulnerable populations during heat
      events.
AB  - The frequency and intensity of hot weather events are expected to increase
      globally, threatening human health, especially among the elderly, poor, and
      chronically ill. Current literature indicates that emergency preparedness plans,
      heat health warning systems, and related interventions may not be reaching or
      supporting behavior change among those most vulnerable in heat events. Using a
      qualitative multiple case study design, we comprehensively examined practices of
      these populations to stay cool during hot weather ("cooling behaviors") in four
      U.S. cities with documented racial/ethnic and socio-economic disparities and
      diverse heat preparedness strategies: Phoenix, Arizona; Detroit, Michigan; New
      York City, New York; and Philadelphia, Pennsylvania. Based on semi-structured in
      depth interviews we conducted with 173 community members and organizational
      leaders during 2009-2010, we assessed why vulnerable populations do or do not
      participate in health-promoting behaviors at home or in their community during
      heat events, inquiring about perceptions of heat-related threats and
      vulnerability and the role of social support. While vulnerable populations often
      recognize heat's potential health threats, many overlook or disassociate from
      risk factors or rely on experiences living in or visiting warmer climates as a
      protective factor. Many adopt basic cooling behaviors, but unknowingly harmful
      behaviors such as improper use of fans and heating and cooling systems are also
      adopted. Decision-making related to commonly promoted behaviors such as air
      conditioner use and cooling center attendance is complex, and these resources are
      often inaccessible financially, physically, or culturally. Interviewees expressed
      how interpersonal, intergenerational relationships are generally but not always
      protective, where peer relationships are a valuable mechanism for facilitating
      cooling behaviors among the elderly during heat events. To prevent disparities in
      heat morbidity and mortality in an increasingly changing climate, we note the
      implications of local context, and we broadly inform heat preparedness plans,
      interventions, and messages by sharing the perspectives and words of community
      members representing vulnerable populations and leaders who work most closely
      with them.

PMID- 29375196
TI  - Disruption, not displacement: Environmental variability and temporary migration
      in Bangladesh.
AB  - Mass migration is one of the most concerning potential outcomes of global climate
      change. Recent research into environmentally induced migration suggests that
      relationship is much more complicated than originally posited by the
      'environmental refugee' hypothesis. Climate change is likely to increase
      migration in some cases and reduce it in others, and these movements will more
      often be temporary and short term than permanent and long term. However, few
      large-sample studies have examined the evolution of temporary migration under
      changing environmental conditions. To address this gap, we measure the extent to
      which temperature, precipitation, and flooding can predict temporary migration in
      Matlab, Bangladesh. Our analysis incorporates high-frequency demographic
      surveillance data, a discrete time event history approach, and a range of
      sociodemographic and contextual controls. This approach reveals that migration
      declines immediately after flooding but quickly returns to normal. In contrast,
      optimal precipitation and high temperatures have sustained positive effects on
      temporary migration that persist over one to two year periods. Building on
      previous studies of long-term migration, these results challenge the common
      assumption that flooding, precipitation extremes and high temperatures will
      consistently increase temporary migration. Instead, our results are consistent
      with a livelihoods interpretation of environmental migration in which households
      draw on a range of strategies to cope with environmental variability.

PMID- 29375197
TI  - Nuclear Translocation of SGPP-1 and Decrease of SGPL-1 Activity Contribute to
      Sphingolipid Rheostat Regulation of Inflammatory Dendritic Cells.
AB  - A balanced sphingolipid rheostat is indispensable for dendritic cell function and
      survival and thus initiation of an immune response. Sphingolipid levels are
      dynamically maintained by the action of sphingolipid enzymes of which sphingosine
      kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the
      balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and
      SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate.
      TLR-dependent activation caused SGPL-1 protein downregulation with subsequent
      decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence
      microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive
      dendritic cells and was translocated into the cytoplasmatic compartment upon
      inflammatory stimulation resulting in dephosphorylation of S1P. Mass
      spectrometric determination showed that a part of the resulting sphingosine was
      released from the cell, increasing extracellular levels. Another route of
      diminishing intracellular S1P was possibly taken by its export via ATP-binding
      cassette transporter C1 which was upregulated in array analysis, while the S1P
      transporter, spinster homolog 2, was not relevant in dendritic cells. These
      investigations newly describe the sequential expression and localization of the
      endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to
      the sphingolipid rheostat in inflammation.

PMID- 29375198
TI  - A Prospective, Double-Blind, Randomized, Controlled Clinical Trial in the
      Gingivitis Prevention with an Oligomeric Proanthocyanidin Nutritional Supplement.
AB  - Aim: To evaluate the effectiveness on tissue response of the new nutritional
      supplement made of oligomeric proanthocyanidins in induced gingivitis after 21
      days of use. Material and Methods: A prospective, double-blind, randomized,
      controlled clinical trial was carried out on 20 patients; it is divided into an
      experimental group and a control group after fulfilling the selection criteria.
      Patients had to come 4 times during the study to register the Silness and Loe
      index, the gingival bleeding index, the plaque index, the inflammatory crevicular
      fluid study (IL6), and the changes in the brightness of the gingiva. No
      complementary hygiene methods were allowed during the 21 days. Results: The
      Silness and Loe index was higher in the control group than in the experimental
      group, reaching a twofold difference between the groups (p < 0.0001). The
      gingival bleeding index also supports this fact, since the bleeding was lower in
      the experimental group (p < 0.005). However, the dental plaque on the tooth
      surface according to the plaque index was 33% higher in the experimental group (p
      < 0.006). Some differences in the IL-6 were found in the crevicular fluid (p <
      0.0001). Conclusion: Oligomeric proanthocyanidins have an effect on the
      periodontal tissue's health. No effects on the accumulation of plaque on the
      tooth surface were found, so further studies are needed to determine the nature
      of the plaque.

PMID- 29375199
TI  - Corrigendum to "Metalloproteinases and Their Tissue Inhibitors in Comparison
      between Different Chronic Pneumopathies in the Horse".
AB  - [This corrects the article DOI: 10.1155/2015/569512.].

PMID- 29375200
TI  - Mouse Thyroid Gland Changes in Aging: Implication of Galectin-3 and
      Sphingomyelinase.
AB  - Prevalence of thyroid dysfunction and its impact on cognition in older people has
      been demonstrated, but many points remain unclarified. In order to study the
      effect of aging on the thyroid gland, we compared the thyroid gland of very old
      mice with that of younger ones. We have first investigated the changes of thyroid
      microstructure and the possibility that molecules involved in thyroid function
      might be associated with structural changes. Results from this study indicate
      changes in the height of the thyrocytes and in the amplitude of interfollicular
      spaces, anomalous expression/localization of thyrotropin, thyrotropin receptor,
      and thyroglobulin aging. Thyrotropin and thyrotropin receptor are upregulated and
      are distributed inside the colloid while thyroglobulin fills the interfollicular
      spaces. In an approach aimed at defining the behavior of molecules that change in
      different physiopathological conditions of thyroid, such as galectin-3 and
      sphingomyelinase, we then wondered what was their behavior in the thyroid gland
      in aging. Importantly, in comparison with the thyroid of young animals, we have
      found a higher expression of galectin-3 and a delocalization of neutral
      sphingomyelinase in the thyroid of old animals. A possible relationship between
      galectin-3, neutral sphingomyelinase, and aging has been discussed.

PMID- 29375201
TI  - Influences of background noise on infants and children.
AB  - The goal of this review is to provide a high-level, selected overview of the
      consequences of background noise on health, perception, cognition, and learning
      during early development, with a specific focus on how noise may impair speech
      comprehension and language learning (e.g., via masking). Although much of the
      existing literature has focused on adults, research shows that infants and young
      children are relatively disadvantaged at listening in noise. Consequently, a
      major goal is to consider how background noise may affect young children, who
      must learn and develop language in noisy environments despite being
      simultaneously less equipped to do so.

PMID- 29375202
TI  - Drug-eluting beads transarterial chemoembolization for hepatocellular carcinoma:
      Current state of the art.
AB  - Transarterial chemoembolization (TACE) represents the current gold standard for
      hepatocellular carcinoma (HCC) patients in intermediate stage. Conventional TACE
      (cTACE) is performed with the injection of an emulsion of a chemotherapeutic drug
      with lipiodol into the artery feeding the tumoral nodules, followed by
      embolization of the same vessel to obtain a synergistic effect of drug cytotoxic
      activity and ischemia. Aim of this review is to summarize the main
      characteristics of drug-eluting beads (DEB)-TACE and the clinical results
      reported so far in the literature. A literature search was conducted using PubMed
      until June 2017. In order to overcome the drawbacks of cTACE, namely lack of
      standardization and unpredictability of outcomes, non-absorbable embolic
      microspheres charged with cytotoxic agents (DEBs) have been developed. DEBs are
      able to simultaneously exert both the therapeutic components of TACE, either drug
      carrier function and embolization, unlike cTACE in which applying the embolic
      agent is a second moment after drug injection. This way, risk of systemic drug
      release is minimal due to both high-affinity carrier activity of DEBs and absence
      of a time interval between injection and embolization. However, despite promising
      results of preliminary studies, clear evidence of superiority of DEB-TACE over
      cTACE is still lacking. A number of novel technical devices are actually in
      development in the field of loco-regional treatments for HCC, but only a few of
      them have entered the clinical arena. In absence of well-designed randomized
      controlled trials, the decision on whether use DEB-TACE or cTACE is still
      controversial.

PMID- 29375203
TI  - Antifibrogenic effects of vitamin D derivatives on mouse pancreatic stellate
      cells.
AB  - AIM: To study the molecular effects of three different D-vitamins, vitamin D2,
      vitamin D3 and calcipotriol, in pancreatic stellate cells (PSCs). METHODS:
      Quiescent PSCs were isolated from mouse pancreas and activated in vitro by
      seeding on plastic surfaces. The cells were exposed to D-vitamins as primary
      cultures (early-activated PSCs) and upon re-culturing (fully-activated cells).
      Exhibition of vitamin A-containing lipid droplets was visualized by oil-red
      staining. Expression of alpha-smooth muscle actin (alpha-SMA), a marker of PSC
      activation, was monitored by immunofluorescence and immunoblot analysis. The rate
      of DNA synthesis was quantified by 5-bromo-2'-deoxyuridine (BrdU) incorporation
      assays. Real-time PCR was employed to monitor gene expression, and protein levels
      of interleukin-6 (IL-6) were measured by ELISA. Uptake of proline was determined
      using 18F-proline. RESULTS: Sustained culture of originally quiescent PSCs
      induced cell proliferation, loss of lipid droplets and exhibition of stress
      fibers, indicating cell activation. When added to PSCs in primary culture, all
      three D-vitamins diminished expression of alpha-SMA (to 32%-39% of the level of
      control cells; P < 0.05) and increased the storage of lipids (scores from 1.97
      2.15 on a scale from 0-3; controls: 1.49; P < 0.05). No such effects were
      observed when Dvitamins were added to fully-activated cells, while incorporation
      of BrdU remained unaffected under both experimental conditions. Treatment of re
      cultured PSCs with Dvitamins was associated with lower expression of IL-6 (-42%
      to -49%; P < 0.05; also confirmed at the protein level) and increased expression
      of the vitamin D receptor gene (209%-321% vs controls; P < 0.05). There was no
      effect of Dvitamins on the expression of transforming growth factor-beta1 and
      collagen type 1 (chain alpha1). The lowest uptake of proline, a main component of
      collagen, was observed in calcipotriol-treated PSCs. CONCLUSION: The three D
      vitamins inhibit, with similar efficiencies, activation of PSCs in vitro, but
      cannot reverse the phenotype once the cells are fully activated.

PMID- 29375204
TI  - Metabolic and hepatic effects of liraglutide, obeticholic acid and elafibranor in
      diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis.
AB  - AIM: To evaluate the pharmacodynamics of compounds in clinical development for
      nonalcoholic steatohepatitis (NASH) in obese mouse models of biopsy-confirmed
      NASH. METHODS: Male wild-type C57BL/6J mice (DIO-NASH) and Lep ob/ob (ob/ob-NASH)
      mice were fed a diet high in trans-fat (40%), fructose (20%) and cholesterol (2%)
      for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver
      biopsy for confirmation and stratification of liver steatosis and fibrosis, using
      the nonalcoholic fatty liver disease activity score (NAS) and fibrosis staging
      system. The mice were kept on the diet and received vehicle, liraglutide (0.2
      mg/kg, SC, BID), obeticholic acid (OCA, 30 mg/kg PO, QD), or elafibranor (30
      mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on
      changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores.
      In addition, compound effects were evaluated by quantitative liver histology,
      including percent fractional area of liver fat, galectin-3, and collagen 1a1.
      RESULTS: Liraglutide and elafibranor, but not OCA, reduced body weight in both
      models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor
      and OCA reduced histopathological scores of hepatic steatosis and inflammation in
      both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA
      reduced total liver fat, collagen 1a1, and galectin-3 content, driven by
      significant reductions in liver weight. The individual drug effects on NASH
      histological endpoints were supported by global gene expression (RNA sequencing)
      and liver lipid biochemistry. CONCLUSION: DIO-NASH and ob/ob-NASH mouse models
      show distinct treatment effects of liraglutide, OCA, and elafibranor, being in
      general agreement with corresponding findings in clinical trials for NASH. The
      present data therefore further supports the clinical translatability and utility
      of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic
      efficacy of compounds in preclinical drug development for NASH.

PMID- 29375205
TI  - INT-767 improves histopathological features in a diet-induced ob/ob mouse model
      of biopsy-confirmed non-alcoholic steatohepatitis.
AB  - AIM: To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767
      upon histological endpoints in a rodent model of diet-induced and biopsy
      confirmed non-alcoholic steatohepatitis (NASH). METHODS: The effects of INT-767
      on histological features of NASH were assessed in two studies using Lepob/ob
      (ob/ob) NASH mice fed the AMLN diet (high fat with trans-fat, cholesterol and
      fructose). In a proof-of-concept study, Lepob/ob (ob/ob) NASH mice were first
      dosed with INT-767 (3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared
      INT-767 (3 and 10 mg/kg) to obeticholic acid (OCA) (10 or 30 mg/kg; 16 wk).
      Primary histological endpoints included qualitative and quantitative assessments
      of NASH. Other metabolic and plasma endpoints were also assessed. A comparative
      assessment of INT-767 and OCA effects on drug distribution and hepatic gene
      expression was performed in C57Bl/6 mice on standard chow. C57Bl/6 mice were
      orally dosed with INT-767 or OCA (1-30 mg/kg) for 2 wk, and expression levels of
      candidate genes were assessed by RNA sequencing and tissue drug levels were
      measured by liquid chromatography tandem-mass spectrometry. RESULTS: INT-767 dose
      dependently (3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric
      scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage.
      Quantitative morphometric analyses revealed that INT-767 reduced parenchymal
      collagen area, collagen fiber density, inflammation (assessed by Galectin-3
      immunohistochemistry) and hepatocyte lipid droplet area following INT-767
      treatment. In a comparative study (16 wk), the FXR agonists OCA (10 and 30 mg/kg)
      and INT-767 (3 and 10 mg/kg) both improved NASH histopathology, with INT-767
      exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies
      suggest that both drugs accumulate similarly within the liver and ileum, however,
      the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR
      function. CONCLUSION: These findings confirm the potential utility of FXR and
      dual FXR/TGR5 activation as disease intervention strategies in NASH.

PMID- 29375206
TI  - Novel concept of endoscopic device delivery station system for rapid and tight
      attachment of polyglycolic acid sheet.
AB  - AIM: To evaluate appropriate and rapid polyglycolic acid sheet (PGAs) covering
      time using device delivery station system (DDSS). METHODS: This pilot basic study
      was conducted to evaluate the potential of accurate and rapid PGAs delivery using
      DDSS. Three 11-mo-old female Beagle dogs were used in this study. Two endoscopic
      submucosal dissections (ESDs) 4cm in diameter were performed in lesser curvature
      of middle gastric body and greater curvature of antrum (total 6 ESDs performed).
      DDSS (3 cm length, 12 mm in outer diameter) has 2 chambers which 16 cm2 large 2
      PGAs were stored, and DDSS was attached post ESD ulcers, respectively. Beriplast
      P(r) (CSL Behring K.K., Tokyo, Japan) (combination of fibrin glue and thrombin)
      was applied equally to the artificial ulcer, and tight attachment of 2 PGAs with
      DDSS were completed. The evaluation items were covering times, post ESD bleeding
      and perforation during ESD. RESULTS: The covering time of PGAs (defined as the
      duration from the beginning of endoscope insertion into the mouth to the end of
      the fibrin glue coating process) was 6.07 (4.86-8.29) min. There was no post-ESD
      bleeding (1-7 d after ESD), and there was no perforation during ESD. CONCLUSION:
      DDSS was very useful for rapid delivering and tight attachment of PGAs, and has
      potentials of multi-purpose delivery station system.

PMID- 29375207
TI  - beta-arrestin 2 attenuates lipopolysaccharide-induced liver injury via inhibition
      of TLR4/NF-kappaB signaling pathway-mediated inflammation in mice.
AB  - AIM: To study the role and the possible mechanism of beta-arrestin 2 in
      lipopolysaccharide (LPS)-induced liver injury in vivo and in vitro. METHODS: Male
      beta-arrestin 2+/+ and beta-arrestin 2-/- C57BL/6J mice were used for in vivo
      experiments, and the mouse macrophage cell line RAW264.7 was used for in vitro
      experiments. The animal model was established via intraperitoneal injection of
      LPS or physiological sodium chloride solution. Blood samples and liver tissues
      were collected to analyze liver injury and levels of pro-inflammatory cytokines.
      Cultured cell extracts were collected to analyze the production of pro
      inflammatory cytokines and expression of key molecules involved in the TLR4/NF
      kappaB signaling pathway. RESULTS: Compared with wild-type mice, the beta
      arrestin 2 knockout mice displayed more severe LPS-induced liver injury and
      significantly higher levels of pro-inflammatory cytokines, including interleukin
      (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-10. Compared with the
      control group, pro-inflammatory cytokines (including IL-1beta, IL-6, TNF-alpha,
      and IL-10) produced by RAW264.7 cells in the beta-arrestin 2 siRNA group were
      significantly increased at 6 h after treatment with LPS. Further, key molecules
      involved in the TLR4/NF-kappaB signaling pathway, including phospho-IkappaBalpha
      and phosho-p65, were upregulated. CONCLUSION: beta-arrestin 2 can protect liver
      tissue from LPS-induced injury via inhibition of TLR4/NF-kappaB signaling pathway
      mediated inflammation.

PMID- 29375208
TI  - Hepatitis C virus core protein-induced miR-93-5p up-regulation inhibits
      interferon signaling pathway by targeting IFNAR1.
AB  - AIM: To investigate the mechanism by which hepatitis C virus (HCV) core protein
      induced miR-93-5p up-regulation regulates the interferon (IFN) signaling pathway.
      METHODS: HCV-1b core protein was exogenously expressed in Huh7 cells using
      pcDNA3.1 (+) vector. The expression of miR-93-5p and interferon receptor 1
      (IFNAR1) was measured using quantitative reverse transcription-polymerase chain
      reaction and Western blot. The protein expression and phosphorylation level of
      STAT1 were evaluated by Western blot. The overexpression and silencing of miR-93
      5p and IFNAR1 were performed using miR-93-5p agomir and antagomir, and pcDNA3.1
      IFNAR1 and IFNAR1 siRNA, respectively. Luciferase assay was used to identify
      whether IFNAR1 is a target of miR-93-5p. Cellular experiments were also
      conducted. RESULTS: Serum miR-93-5p level was increased in patients with HCV-1b
      infection and decreased to normal level after HCV-1b clearance, but persistently
      increased in those with pegylated interferon-alpha resistance, compared with
      healthy subjects. Serum miR-93-5p expression had an AUC value of 0.8359 in
      distinguishing patients with pegylated interferon-alpha resistance from those
      with pegylated interferon-alpha sensitivity. HCV-1b core protein increased miR-93
      5p expression and induced inactivation of the IFN signaling pathway in Huh7
      cells. Furthermore, IFNAR1 was identified as a direct target of miR-93-5p, and
      IFNAR1 restore could rescue miR-93-5p-reduced STAT1 phosphorylation, suggesting
      that the miR-93-5p-IFNAR1 axis regulates the IFN signaling pathway. CONCLUSION:
      HCV-1b core protein-induced miR-93-5p up-regulation inhibits the IFN signaling
      pathway by directly targeting IFNAR1, and the miR-93-5p-IFNAR1 axis regulates
      STAT1 phosphorylation. This axis may be a potential therapeutic target for HCV-1b
      infection.

PMID- 29375209
TI  - Transplantation of bone marrow-derived endothelial progenitor cells and
      hepatocyte stem cells from liver fibrosis rats ameliorates liver fibrosis.
AB  - AIM: To explore the effectiveness for treating liver fibrosis by combined
      transplantation of bone marrow-derived endothelial progenitor cells (BM-EPCs) and
      bone marrow-derived hepatocyte stem cells (BDHSCs) from the liver fibrosis
      environment. METHODS: The liver fibrosis rat models were induced with carbon
      tetrachloride injections for 6 wk. BM-EPCs from rats with liver fibrosis were
      obtained by different rates of adherence and culture induction. BDHSCs from rats
      with liver fibrosis were isolated by magnetic bead cell sorting. Tracing analysis
      was conducted by labeling EPCs with PKH26 in vitro to show EPC location in the
      liver. Finally, BM-EPCs and/or BDHSCs transplantation into rats with liver
      fibrosis were performed to evaluate the effectiveness of BM-EPCs and/or BDHSCs on
      liver fibrosis. RESULTS: Normal functional BM-EPCs from liver fibrosis rats were
      successfully obtained. The co-expression level of CD133 and VEGFR2 was 63.9% +/-
      2.15%. Transplanted BM-EPCs were located primarily in/near hepatic sinusoids. The
      combined transplantation of BM-EPCs and BDHSCs promoted hepatic
      neovascularization, liver regeneration and liver function, and decreased collagen
      formation and liver fibrosis degree. The VEGF levels were increased in the BM
      EPCs (707.10 +/- 54.32) and BM-EPCs/BDHSCs group (615.42 +/- 42.96), compared
      with those in the model group and BDHSCs group (P < 0.05). Combination of BM
      EPCs/BDHSCs transplantation induced maximal up-regulation of PCNA protein and HGF
      mRNA levels. The levels of alanine aminotransferase (AST), aspartate
      aminotransferase, total bilirubin (TBIL), prothrombin time (PT) and activated
      partial thromboplastin time in the BM-EPCs/BDHSCs group were significantly
      improved, to be equivalent to normal levels (P > 0.05) compared with those in the
      BDHSC (AST, TBIL and PT, P < 0.05) and BM-EPCs (TBIL and PT, P < 0.05) groups.
      Transplantation of BM-EPCs/BDHSCs combination significantly reduced the degree of
      liver fibrosis (staging score of 1.75 +/- 0.25 vs BDHSCs 2.88 +/- 0.23 or BM-EPCs
      2.75 +/- 0.16, P < 0.05). CONCLUSION: The combined transplantation exhibited
      maximal therapeutic effect compared to that of transplantation of BM-EPCs or
      BDHSCs alone. Combined transplantation of autogenous BM-EPCs and BDHSCs may
      represent a promising strategy for the treatment of liver fibrosis, which would
      eventually prevent cirrhosis and liver cancer.

PMID- 29375210
TI  - Genetic variants of interferon regulatory factor 5 associated with chronic
      hepatitis B infection.
AB  - AIM: To investigate possible effects of IRF5 polymorphisms in the 3' UTR region
      of the IFR5 locus on susceptibility to hepatitis B virus (HBV) infection and
      progression of liver diseases among clinically classified Vietnamese patients.
      METHODS: Four IFR5 SNPs (rs13242262A/T, rs77416878C/T, rs10488630A/G, and
      rs2280714T/C) were genotyped in clinically classified HBV patients [chronic
      hepatitis B (CHB). n = 99; liver cirrhosis (LC), n = 131; hepatocellular
      carcinoma (HCC), n = 149] and in 242 healthy controls by direct sequencing and
      TaqMan real-time PCR assays. RESULTS: Comparing patients and controls, no
      significant association was observed for the four IFR5 variants. However, the
      alleles rs13242262T and rs10488630G contributed to an increased risk of liver
      cirrhosis (LC vs CHB: OR = 1.5, 95%CI: 1.1-2.3, adjusted P = 0.04; LC vs CHB: OR
      = 1.7, 95%CI: 1.1-2.6, adjusted P = 0.019). Haplotype IRF5*TCGT constructed from
      4 SNPs was observed frequently in LC compared to CHB patients (OR = 2.1, 95%CI:
      1.2-3.3, adjusted P = 0.008). Haplotype IRF5*TCAT occurred rather among CHB
      patients than in the other HBV patient groups (LC vs CHB: OR = 0.4, 95%CI: 0.2
      0.8, adjusted P = 0.03; HCC vs CHB: OR = 0.3, 95%CI: 0.15-0.7, adjusted P =
      0.003). The IRF5*TCAT haplotype was also associated with increased levels of ALT,
      AST and bilirubin. CONCLUSION: Our study shows that IFR5 variants may contribute
      as a host factor in determining the pathogenesis in chronic HBV infections.

PMID- 29375211
TI  - Timing of surgery after neoadjuvant chemotherapy for gastric cancer: Impact on
      outcomes.
AB  - AIM: To evaluate whether the neoadjuvant chemotherapy (NACT)-surgery interval
      time significantly impacts the pathological complete response (pCR) rate and long
      term survival. METHODS: One hundred and seventy-six patients with gastric cancer
      undergoing NACT and a planned gastrectomy at the Chinese PLA General Hospital
      were selected from January 2011 to January 2017. Univariate and multivariable
      analyses were used to investigate the impact of NACT-surgery interval time (< 4
      wk, 4-6 wk, and > 6 wk) on pCR rate and overall survival (OS). RESULTS: The NACT
      surgery interval time and clinician T stage were independent predictors of pCR.
      The interval time > 6 wk was associated with a 74% higher odds of pCR as compared
      with an interval time of 4-6 wk (P = 0.044), while the odds ratio (OR) of
      clinical T3vs clinical T4 stage for pCR was 2.90 (95%CI: 1.04-8.01, P = 0.041).
      In Cox regression analysis of long-term survival, post-neoadjuvant therapy
      pathological N (ypN) stage significantly impacted OS (N0vs N3: HR = 0.16, 95%CI:
      0.37-0.70, P = 0.015; N1vs N3: HR = 0.14, 95%CI: 0.02-0.81, P = 0.029) and
      disease-free survival (DFS) (N0vs N3: HR = 0.11, 95%CI: 0.24-0.52, P = 0.005;
      N1vs N3: HR = 0.17, 95%CI: 0.02-0.71, P = 0.020). The surgical procedure also had
      a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total
      gastrectomy was 0.12 (95%CI: 0.33-0.42, P = 0.001) for OS, and 0.13 (95%CI: 0.36
      0.44, P = 0.001) for DFS. CONCLUSION: The NACT-surgery interval time is
      associated with pCR but has no impact on survival, and an interval time > 6 wk
      has a relatively high odds of pCR.

PMID- 29375212
TI  - Predictive and prognostic value of serum AFP level and its dynamic changes in
      advanced gastric cancer patients with elevated serum AFP.
AB  - AIM: To investigate predictive and prognostic value of serum alpha-fetoprotein
      (AFP) level and its dynamic changes in patients with advanced gastric cancer with
      elevated serum AFP (AFPAGC). METHODS: One hundred and five patients with AFPAGC
      were enrolled in the study, and all of them underwent at least one cycle of
      systemic chemotherapy at our institute and had serum AFP >= 20 ng/mL at diagnosis
      or recurrence. Clinicopathologic features, serum AFP level at diagnosis and
      changes during treatment, first-line chemotherapy regimens, efficacy and
      toxicity, and survival information were collected. A Person's chi2 or Fisher's
      exact test was used to measure the differences between variables. Survival
      prognostic factors were investigated using the Kaplan-Meier method and Cox
      regression. RESULTS: Median serum AFP level was 161.7 ng/mL (range, 22.9-2557110
      ng/mL). Objective response rates (ORR) was significantly lower in the AFP >= 160
      ng/mL group than in the AFP < 160 ng/mL group (30.4% vs 68.3%, P < 0.001). ORR to
      doublet regimens was significantly lower in the AFP >= 160 ng/mL group, whereas
      ORR to triplet regimens was similar between the two groups. Liver metastasis rate
      was significantly higher in the AFP >= 160 ng/mL group than in the AFP < 160
      ng/mL (69.8% vs 50.0%, P < 0.001). Overall survival (OS) in the two cohorts did
      not show any significant difference (P = 0.712). Dynamic changes of AFP were
      consistent with response to chemotherapy, and median OS of patients with a serum
      AFP decline >= 50% and those with a serum AFP decline < 50% was 17.5 m and 10.0
      m, respectively (P = 0.003). Hepatic (P = 0.005), peritoneal (P < 0.001), non
      regional lymph node metastasis (P < 0.001), and portal vein tumor thrombus (PVTT)
      (P = 0.042) were identified as independent prognostic factors for AFPAGC.
      CONCLUSION: Real-time examination of AFP has great predictive and prognostic
      value for managing AFPAGC. For those with markedly elevated AFP, triplet regimens
      may be a better choice.

PMID- 29375213
TI  - Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?
AB  - AIM: To investigate the neoadjuvant chemotherapy (NAC) effect on the survival of
      patients with proper stomach cancer submitted to D2 gastrectomy. METHODS: We
      proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO
      meeting abstracts as well as computerized use of the Cochrane Library for
      randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S)
      with surgery alone (SA) for gastric cancer (GC). The primary outcome was the
      overall survival rate. Secondary outcomes were the site of the primary tumor,
      extension of node dissection according to Japanese Gastric Cancer Association
      (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival
      (DFS) rates, clinical and pathological response rates and resectability rates
      after perioperative treatment. RESULTS: We identified a total of 16 randomized
      controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the
      period from January 1993 - March 2017. Only 6 of these studies were well
      designed, structured trials in which the type of lymph node (LN) dissection
      performed or at least suggested in the trial protocol was reported. Two out of
      three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to
      show survival benefit in the NAC arm. In the third RCT, the survival rate was not
      even reported, and the primary end points were the clinical outcomes of surgery
      with and without NAC. In the remaining three RCTs, D2 lymph node dissection was
      performed in less than 50% of cases or only recommended in the "Study Treatment"
      protocol without any description in the results of the procedure really perfomed.
      In one of the two studies, the benefit of NAC was evident only for
      esophagogastric junction (EGJ) cancers. In the second study, there was no overall
      survival benefit of NAC. In the last trial, which documented a survival benefit
      for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and
      more than one-fourth of patients did not have a proper stomach cancer.
      Additionally, several patients did not receive resectional surgery. Furthermore,
      the survival rates of international reference centers that provide adequate
      surgery for homogeneous stomach cancer patients' populations are even higher than
      the survival rates reported after NAC followed by incomplete surgery. CONCLUSION:
      NAC for GC has been rapidly introduced in international western guidelines
      without an evidence-based medicine-related demonstration of its efficacy for a
      homogeneous population of patients with only stomach tumors submitted to adequate
      surgery following JGCA guidelines with extended (D2) LN dissection. Additional
      larger sample-size multicentre RCTs comparing the newer NAC regimens including
      molecular therapies followed by adequate extended surgery with surgery alone are
      needed.

PMID- 29375214
TI  - Clinically diagnosed late-onset fulminant Wilson's disease without cirrhosis: A
      case report.
AB  - A 64-year-old woman was referred to our hospital with jaundice of the bulbar
      conjunctiva and general fatigue. After admission, she developed hepatic
      encephalopathy and was diagnosed with fulminant hepatitis based on the American
      Association for the Study of Liver Disease (AASLD) position paper. Afterwards,
      additional laboratory findings revealed that serum ceruloplasmin levels were
      reduced, urinary copper levels were greatly elevated and Wilson's disease (WD)
      specific routine tests were positive, but the Kayser-Fleischer ring was not
      clear. Based on the AASLD practice guidelines for the diagnosis and treatment of
      WD, the patient was ultimately diagnosed with fulminant WD. Then, administration
      of penicillamine and zinc acetate was initiated; however, the patient
      unfortunately died from acute pneumonia on the 28th day of hospitalization. At
      autopsy, the liver did not show a bridging pattern of fibrosis suggestive of
      chronic liver injury. Here, we present the case of a patient with clinically
      diagnosed late-onset fulminant WD without cirrhosis, who had positive disease
      specific routine tests.

PMID- 29375215
TI  - Mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm: A case
      report.
AB  - Mass forming chronic pancreatitis is very rare. Diagnosis could be done by the
      pathologic findings of focal inflammatory fibrosis without evidence of tumor in
      pancreas. A 34-year-old man presented with right upper abdominal pain for a few
      weeks and slightly elevated bilirubin level on clinical findings. Radiological
      findings of multidetector-row computed tomography, magnetic resonance (MR)
      imaging with MR cholangiopancreatography and endoscopic ultrasonography revealed
      focal branch pancreatic duct dilatation with surrounding delayed enhancing solid
      component at uncinate process and head of pancreas, suggesting branch duct type
      intraductal papillary mucinous neoplasm. Surgery was done and pathology revealed
      the focal chronic inflammation, fibrosis, and branch duct dilatation. Herein, I
      would like to report the first case report of mass forming chronic pancreatitis
      mimicking pancreatic cystic neoplasm.

PMID- 29375216
TI  - Successful treatment of a giant ossified benign mesenteric schwannoma.
AB  - Primary benign schwannoma of the mesentery is extremely rare. To date, only 9
      cases have been reported in the English literature, while mesenteric schwannoma
      with ossified degeneration has not been reported thus far. In the present study,
      we present the first giant ossified benign mesenteric schwannoma in a 58-year-old
      female. Ultrasound, computed tomography and magnetic resonance imaging were used,
      but it was still difficult to determine the definitive location and diagnose the
      mass. By laparotomy, a 10.0 cm * 9.0 cm * 9.0 cm giant mass was found in the
      mesentery and was then completely resected. Microscopically, the tumour located
      in the mesentery mainly consisted of spindle-shaped cells with a palisading
      arrangement. Some areas of the tumour were ossified, and a true metaplastic bone
      formation was observed, with the presence of bone lamellae and osteoblasts.
      Immunohistochemical investigation of the tumour located in the mesentery showed
      that the staining for the S-100 protein was strongly positive, while the
      stainings of SMA, CD34, CD117 and DOG-1 were negative. The cell proliferation
      index, measured with Ki67 staining, was less than 3%. Finally, a giant ossified
      benign mesenteric schwannoma was diagnosed. After surgery, the patient was
      followed up for a period of 43 mo, during which she remained well, with no
      evidence of tumour recurrence.

PMID- 29375218
TI  - Our Stance towards the 2017 ACC/AHA High Blood Pressure Clinical Practice
      Guideline: Has the Pendulum Swung Too Far?

PMID- 29375217
TI  - Candida accommodates non-culturable Helicobacter pylori in its vacuole - Koch's
      postulates aren't applicable.
AB  - The following are the responses to the "letter to the editor" ("Helicobacter is
      preserved in yeast vacuoles! Does Koch's postulates confirm it?") authored by
      Nader Alipour and Nasrin Gaeini that rejected the methods, results, discussions
      and conclusions summarized in the review article authored by Siavoshi F and
      Saniee P. In the article, 7 papers, published between 1998 and 2013, were
      reviewed. The 7 papers had been reviewed and judged very carefully by the
      assigned expertise of the journals involved, including the reviewers of the World
      Journal of Gastroenterology (WJG), before publication. In the review article, 121
      references were used to verify the methods, results and discussions of these 7
      papers. The review article was edited by the trustworthy British editor of the
      (WJG), and the final version was rechecked and finally accepted by the reviewers
      of (WJG). None of the reviewers made comments like those in this "letter to the
      editor", especially the humorous comments, which seem unprofessional and
      nonscientific. Above all, the authors' comments show a lack of understanding of
      basic and advanced microbiology, e.g. bacterial endosymbiosis in eukaryotic
      cells. Accordingly, their comments all through the letter contain misconceptions.
      The comments are mostly based on personal conclusions, without any scientific
      support. It would have been beneficial if the letter had been reviewed by the
      reviewers of the article by Siavoshi and Saniee.

PMID- 29375219
TI  - TIMI and GRACE Risk Scores Predict Both Short-Term and Long-Term Outcomes in
      Chinese Patients with Acute Myocardial Infarction.
AB  - Background: Little is known about the long-term prognostic values of both
      thrombolysis in myocardial infarction (TIMI) and Global Registry of Acute Cardiac
      Events (GRACE) risk scores (RSs) to the Asian ethnicity. The purpose of this
      study is to compare the usefulness of these two scores in risk stratification and
      prediction of long-term (up to 3 years) outcomes for Chinese patients with
      myocardial infarction (MI). Methods: We calculated the TIMI and GRACE RSs for 726
      consecutive patients with MI [55.6% with ST-segment elevation (STEMI) and 44.4%
      with non-ST-segment elevation (NSTEMI)]. Results: Although the risk profile of
      our population (median TIMI score = 5 for STEMI, 4 for NSTEMI, and median GRACE
      score = 164) was higher, the in-hospital mortality (7.1% for NSTEMI and 6.7% for
      STEMI) was comparable to that predicted by GRACE RS. The GRACE RS worked well in
      predicting short-term and long-term death (C-statistics range 0.710 to 0.789) and
      triple (death, MI, and stroke) endpoints (C-statistics range 0.695 to 0.764) in
      both subsets of MI. GRACE RS performed significantly better than the TIMIRS in
      predicting 3-year mortality in NSTEMI (p = 0.035) and 1-year and 3-year mortality
      in STEMI (p = 0.028 and 0.009, respectively). Stratification by tertiles of
      GRACERS furnished greater prognostic information versus risk assessment by the
      TIMI RS. Conclusions: The use of RSs revealed a fair to good discriminatory
      accuracy in predicting both short-term and long-term major adverse cardiac events
      in Asian patients with MI. Compared with the simpler TIMI RS, the GRACERS was
      more accurate in predicting long-term mortality.

PMID- 29375220
TI  - Relationship between Fragmented QRS and NT-proBNP in Patients with ST Elevation
      Myocardial Infarction Who Underwent Primary Percutaneous Coronary Intervention.
AB  - Background: To investigate the relationship between the presence of fragmented
      QRS (fQRS) on electrocardiogram (ECG) and plasma NT-proBNP levels in patients
      with ST-elevation myocardial infarction (STEMI) who underwent primary
      percutaneous coronary intervention (PCI). The in-hospital prognostic value of the
      presence of fQRS was also assessed. Methods: In this retrospective study, 216
      patients with STEMI who were undergoing primary PCI were included. fQRS was
      identified in ECG following primary PCI. The fQRS included various morphologies
      of the QRS (< 120 ms), which included an additional R wave (R') or notching in
      the nadir of the S wave, or > 1R' (fragmentation) in 2 contiguous leads,
      corresponding to a major coronary artery territory. N-terminal pro-brain
      natriuretic peptide (NT-proBNP) levels were measured immediately, 24 and 48 hours
      after admition and the peak level was adopted. Patients were divided into two
      groups based on the presence (n = 126) or absence (n = 90) of a fQRS on ECG.
      Results: NT-proBNP level was found to be significantly higher in fQRS (+) group
      compared to the fQRS (-) group (p < 0.001). The in-hospital advanced heart
      failure were found to be significantly more frequent in the fQRS (+) group. In
      logistic regression analysis, the fQRS >= 3 leads, fQRS in anterior leads, and NT
      proBNP were independently related with in-hospital major adverse cardiac events
      that includes cardiovascular mortality, reinfarction, advanced heart failure,
      repeat target vessel revascularization, ventricular arrhythmias, atrioventricular
      block or sroke in the hospital. The area under the curve using the NTpro-BNP
      level for the prediction of fQRS was 0.809. Conclusions: The presence of fQRS is
      significantly associated with NT-proBNP and left ventricular ejection fraction,
      which can predict left ventricular function in patients with STEMI. fQRS is a
      prognostic marker of impaired regional ventricular systolic function.

PMID- 29375221
TI  - The Association between Monocyte HDL-C Ratio and SYNTAX Score and SYNTAX Score II
      in STEMI Patients Treated with Primary PCI.
AB  - Background: Monocyte to high-density-lipoprotein cholesterol ratio (MHR) simply
      reflects proatherogenic and antiatherogenic balance and high level of this ratio
      is associated with severity of coronary atherosclerosis and cardiac events. We
      investigated the association between MHR and coronary artery disease severity
      using SYNTAX score and SYNTAX score II (SSII) in ST-elevation myocardial
      infarction (STEMI) patients treated with primary percutaneous coronary
      intervention (pPCI). Methods: A total of 315 consecutive patients with STEMI who
      underwent pPCI from January 2014 to January 2016 were enrolled. After exclusion
      264 patients remained in the study population. Patients were divided into 2
      groups according to median SSII [SSII <= 34.2 as low group (n = 132) and > 34.2
      as high group (n = 132)]. Results: Median value of MHR was 10.5 in SSII low group
      and 16.1 in SSII high group (p < 0.001). There was a strong correlation between
      MHR and SSII (r = 0.580, p < 0.001). Diabetes mellitus [odds ratio (OR): 8.604;
      95% confidence interval (CI): 2.469-29.978], glomerular filtration rate (OR:
      0.961; 95% CI: 0.939-0.983), infarct related artery of left anterior descending
      (LAD) (OR: 7.325; 95% CI: 2.262-23.723), SYNTAX score (OR: 1.422; 95% CI: 1.275
      1.585), neutrophil to lymphocyte ratio (NLR) (OR: 1.156; 95% CI: 1.058-1.264) and
      MHR (OR: 1.027; 95% CI: 1.013-1.041) were independent predictors of SSII > 34.2
      in multivariate analysis. Conclusions: MHR could be a better parameter than NLR
      and C-reactive protein at predicting severity of coronary artery disease in STEMI
      patients treated with pPCI.

PMID- 29375222
TI  - Crusade Microcatheter-Facilitated Reverse Wire Technique for Revascularization of
      Bifurcation Lesions of Coronary Arteries.
AB  - Background: This study aims to analyze the lesion characteristics of bifurcations
      that required reverse wire technique and the efficacy and safety of this
      technique in approaching branches with a highly angulated take-off. Methods: We
      enrolled patients in whom reverse wire technique was used after failed
      conventional antegrade wiring with the support of a Crusade catheter. The study
      endpoints were the technical success defined as succeeding in sending the
      reversely bent wire to the targeted branches without complications and the
      procedural success defined as succeeding in revascularization of the bifurcation
      lesions without complications. Results: Among 158 patients with bifurcation
      lesions undergoing percutaneous coronary intervention using a Crusade catheter to
      facilitate wiring, 23 (14.6%) requiring the reverse wire technique in an attempt
      to access branches of the bifurcation lesions with an acutely angulated take-off
      were enrolled for analysis. The obtainable angle of take-off was 162.9 +/- 4.7
      degrees. For the parent vessel, the ostium of the targeted branch, and
      nontargeted branch, the minimal luminal diameters were 0.3 +/- 0.5 mm, 0.4 +/-
      0.2 mm, and 1.8 +/- 0.5 mm, respectively; the diameter stenosis were 88.8 +/-
      18.5%, 83.0 +/- 7.3%, and 32.0 +/- 14.5%, respectively. Technical and procedural
      success was achieved in 22 cases (96% for both). Conclusions: We showed in the
      present study that the reverse wire technique is effective and safe for
      approaching highly angulated branches of bifurcation lesions and consequently for
      complete revascularization of difficult bifurcation lesions.

PMID- 29375223
TI  - Use of Internal Endoconduit for Unfavorable Iliac Artery Anatomy in Patients
      Undergoing Transcatheter Aortic Valve Replacement - A Single Center Experience.
AB  - Background: Transfemoral (TF) access is associated with lower rates of surgical
      conversion and mortality compared with non-TF access for transcatheter aortic
      valve replacement (TAVR). Therefore, efforts should be made to make this
      procedure even less invasive, allowing more TAVR procedures to be performed
      through femoral access. We herein describe our single-center experience of using
      one-stage percutaneous internal endoconduits for TAVR in patients with
      unfavorable iliac artery anatomy. Methods: Between March 2013 andMarch 2016, 113
      consecutive patients with severe aortic stenosis at high risk for conventional
      cardiac surgery underwent TAVR at the Cheng Hsin General Hospital. The patients
      can be divided into Cohort A (March 2013-December 2014) and Cohort B (January
      2015-March 2016). Results: In the Cohort A, 6 out of the 53 (11.4%) with
      unfavorable iliac artery anatomy were treated by trans-subclavian approach (n =
      3, 5.7%) or direct aortic approach (n = 3, 5.7%); while in the Cohort B, none
      (0%) of the 5 patients with unfavorable iliac artery anatomy among 60 consecutive
      TAVR cases needed non-TF approach (Cohort A vs. Cohort B = 11.4% vs. 0%, p =
      0.024) and they were all successfully treated with the use of an internal
      endoconduit. Conclusions: The use of internal endoconduits can further increase
      the number of patients who can be treated through femoral artery access for TAVR
      and substantially reduce the need of non-TF approaches.

PMID- 29375225
TI  - Low Dose Spironolactone Monotherapy in the Management of Stage I Essential
      Hypertension: A Pilot Randomized, Double-Blind, Placebo-Controlled Trial.
AB  - Background: High blood pressure (BP) is a common chronic disease needs long life
      drug consumption to control. Spironolactone could be used as the fourth-line
      therapy in patients with resistant hypertension. However, there is no study to
      determine the effects of low dose spironolactone as a first line therapy in
      treatment of essential hypertension. The aim of this study is to investigate the
      effect of low dose spironolactone monotherapy in management of essential
      hypertension. Methods: In this double blind randomized clinical trial, 40
      patients who had stage I essential hypertension were randomly divided into two
      groups: intervention group received spironolactone 25 milligram once daily for
      one month and control group received placebo once daily. At the baseline and
      after one month, 24-hour BP holter-monitoring and serum potassium assay were
      done. Results: Systolic BP was reduced from 143.5 +/- 8.2 mmHg to 137.10 +/- 7.57
      mmHg in the intervention group, while it did not change significantly in control
      (between group treatment difference = -4.5 mmHg, p = 0.004). There was no
      significant reduction of diastolic BP in the intervention group in comparison to
      placebo group (between group treatment difference = -1.3 mmHg, p = 0.099).
      Conclusions: Short course monotherapy with low dose spironolactone is effective
      in reducing systolic BP in patients with stage I essential hypertension.

PMID- 29375224
TI  - Safety and Efficacy of Epicardial Ablation of Ventricular Tachyarrhythmias:
      Experience from a Tertiary Referral Center in Taiwan.
AB  - Background: Epicardial catheter ablation has been shown to be an effective
      strategy for treating ventricular arrhythmias (VA). We investigated the efficacy
      and safety from a tertiary referral center in Taiwan. Methods: From 2010 to 2016,
      patients undergoing epicardial ablation for VAs were consecutively enrolled. The
      clinical characteristics, disease entity, electrophysiological studies, and
      ablation outcome were extracted for further analysis. Results: A total of 80
      patients were eligible, including 34 patients for arrhythmogenic right
      ventricular cardiomyopathy (ARVC), 16 for Brugada syndrome (BrS), 13 for
      idiopathic VAs, 11 for idiopathic dilated cardiomyopathy (IDCM), 2 for ischemic
      cardiomyopathy, and 4 for other nonischemic cardiomyopathies (NICM). Epicardial
      ablation rendering VAs non-inducible was achieved in 78 patients (97.5%). There
      were no procedure-related deaths. Major complications were reported in 8 (10.0%)
      patients, including an acute hemopericardium in 5 (6.3%), delayed tamponade in 1
      (1.3%), hemothorax in 1 (1.3%), and major pericardial reaction in 1 (1.3%). Two
      (2.7%) patients died due to causes other than procedure-related deaths. After a
      mean follow-up of 31 +/- 15 months, 20 patients (25.0%) presented with VA
      recurrences, including 13 with ARVC, 1 with BrS, 1 with idiopathic VAs, 4 with
      IDCM, and 1 with other NICM. Conclusions: In this tertiary referral center's
      experience, the complication rate of an epicardial approach was acceptable.
      Patients with NICM displayed a growing trend for a referral for epicardial
      ablation. The long-term follow-up demonstrated that an epicardial ablation for
      idiopathic VAs and BrS was associated with a better prognosis than that for the
      other etiologies.

PMID- 29375226
TI  - Increased Risk of Venous Thromboembolism in Women with Uterine Leiomyoma: A
      Nationwide, Population-Based Case-Control Study.
AB  - Background: Venous thromboembolism (VTE) is a sex-specific disease that has
      different presentations between men and women. Women with uterine leiomyoma can
      present with VTE without exhibiting the traditional risk factors. We investigated
      the relationship between a history of uterine leiomyoma and the risk of VTE using
      the National Health Insurance Research Database (NHIRD). Methods: We conducted a
      retrospective, nationwide, population-based case-control study using the NHIRD.
      We identified 2,282 patients with diagnosed VTE and 392,635 subjects without VTE
      from 2000 to 2013. After development of an age and index diagnosis year frequency
      matched model and propensity score-matched model, 2 models with a case-to-control
      ratio of 1 to 4 were established. Using the diagnosis of uterine leiomyoma as the
      exposure factor, conditional logistic regression was performed to examine the
      association between uterine leiomyoma and VTE. Multiple logistic regression
      analysis was used to investigate the joint effect of uterine leiomyoma and
      comorbid diseases on the risk of VTE. Results: A strong association was observed
      between uterine leiomyoma and VTE in the overall patient model, frequency-matched
      model and propensity score-matched model [p < 0.0001, odds ratio (OR): 1.547; p =
      0.0005, OR: 1.486; p = 0.0405, OR: 1.26, respectively]. In the subgroup analyses,
      women with uterine leiomyoma who were >= 45 years old were less likely to
      experience VTE, but women with uterine leiomyoma and anemia, cancer, coronary
      artery disease or heart failure were more likely to experience VTE. Conclusions:
      Women with uterine leiomyomas have an increased risk of developing VTE,
      especially during reproductive periods or in the presence of specific diseases.

PMID- 29375227
TI  - MiRNA Signaling in Viral Myocarditis Novel and Unique Pathological Features.
AB  - Background: Micro-RNAs (miRNAs) are small non-coding RNAs that modulate many
      target genes. Viral myocarditis is common cardiomyopathy, however, there is an
      absence of effective therapeutic strategies for viral myocarditis (VMC). The
      purpose of this research was to characterize changes in miRNAs expression in VMC
      mice. Methods: Atrial myocytes were infected coxsackievirus B3 and miRNAs
      microarray was performed. miRNAs target predicted and the bioinformatics analysis
      was carried out by gene ontology (GO) and KEGG pathway analysis. To validate the
      results, Difference miRNAs were identified in heart of mice by real-time
      polymerase chain reaction (PCR). Results: We identified 94 miRNAs that were
      differentially expressed (27 were up-regulated and 67 were down-regulated by at
      least 2.0-fold). Real time PCR analysis has confirmed that the expression levels
      of 7 miRNAs up-regulated, 18 miRNAs down-regulated. They were mainly involved in
      protein binding, small GTPase mediated signal transduction, protein
      phosphorylation by GO. Pathway analysis showed that a significant enrichment in
      several pathways related to cAMP signaling pathway, AMPK signaling pathway, RAS
      signaling pathway, Rap1 signaling pathway, ErbB signaling pathway, Oxytocin
      signaling pathway. Conclusions: Our results provide a better understanding of the
      mechanisms of viral myocarditis pathophysiology.

PMID- 29375228
TI  - Balloon Aortic Valvuloplasty in a Premature Neonate with Critical Aortic Valve
      Stenosis Weighing 1493 g.
AB  - The use of balloon aortic valvuloplasty for congenital aortic valve stenosis was
      well established in literatures. However, balloon aortic valvuloplasty performed
      in low body weight neonates had been infrequently reported. Here we report a 5
      day-old premature neonate diagnosed critical aortic valve stenosis. Balloon
      aortic valvuloplasty was performed as first-line therapy while the patient
      weighed only 1493 g. Balloon aortic valvuloplasty went successfully with
      transvalvular pressure gradient decreased from 80 mmHg to 44 mmHg. Aortic
      regurgitation after balloon aortic valvuloplasty was mild. The patient's clinical
      condition stabilized after balloon aortic valvuloplasty and was able to gain
      weight to 2665 g. Our report demonstrates that balloon aortic valvuloplasty is
      possible, safe and efficient as first-line approach for critical aortic valve
      stenosis in neonates with low body weight.

PMID- 29375229
TI  - Coexistence of Gitelman Syndrome and Hypertrophic Cardiomyopathy in a Pregnant
      Woman.
AB  - Gitelman syndrome (GS) is transmitted as an autosomal recessive trait and
      characterized by hypokalemic metabolic alkalosis in combination with significant
      hypomagnesemia and low urinary calcium excretion. The symptoms and severity of
      the disease can vary greatly from one person to another and can range from mild
      to severe. Sudden cardiac arrest has been reported occasionally as well. Here,
      for the first time, we reported a 34-year-old pregnant GS woman who was diagnosed
      to have hypertrophic obstructive cardiomyopathy during her cardiac examination
      for the complaints of palpitation and presyncope.

PMID- 29375230
TI  - Prolonged First-Dose Hypotension Induced by Sacubitril/Valsartan.
AB  - Entresto was recommanded by major guidelines as the frontline therapy for heart
      failure with reduced ejection fraction since its clinical benefit was proved by
      the PARADIGM-HF trial. Angiotensin converting enzyme inhibitors are the
      cornerstone of the treatment of HF. Varying incidences of first-dose hypotension
      have been reported and recognized as a potential limiting factor for prescribing.
      According to previous reports, the onset of hypotension mostly occur 3-5 hours
      after the first dose. However, the pattern of entresto-related hypotension has
      not been reported. We present a case of HF, who had delay onset (about 8 to 18
      hours) and prolonged (3 to 6 days) first-dose hypotension. Further investigation
      is required to illustrate this phenomenon.

PMID- 29375231
TI  - Recruiting an Acute Coronary Team to Perform Emergent Mechanical Thrombectomy in
      Acute Ischemic Stroke Patients: A Successful Case and Team Model in a Local
      Hospital.
AB  - Stroke treatment has entered a new era after the publication of multiple
      randomized trials involving the use of a stent retriever since 2015. In Taiwan,
      the demand for interventional neuroradiologists to perform mechanical
      thrombectomy is high. For this reason, providing this standard care requires
      reshaping of the care model. Here, we report our experience in recruiting an
      acute coronary care team to perform emergent mechanical thrombectomy, which is
      essential in a patient with acute ischemic stroke.

PMID- 29375232
TI  - Acute Myocardial Infarction and Concomitant Stroke as the Manifestations in a
      Patient with Type A Aortic Dissection: A Case Report with Three Years of Follow
      Up.
AB  - A 55-year-old male patient presented with repeated acute retrosternal chest pain.
      Twelve-lead electrocardiogram and cardiac enzymes revealed non-ST elevation
      myocardial infarction. He was treated as non-ST elevation myocardial infarction
      at first. The symptoms of left-sided hemiparesis and aphasia occurred later on
      after admission. The results of emergent brain computed tomography and magnetic
      resonance imagining demonstrated acute stroke. The unusual presentation warned us
      of the possibility of aortic dissection. Besides the reports of heart and vessels
      computed tomography indicated aortic dissection as the underlying cause. Emergent
      surgical repair with preservation of the aortic valve led to a good recovery of
      heart and cerebral function. To the best of our knowledge, there were only three
      cases in the review of literature presenting with acute myocardial infarction and
      concurrent stroke resulting from acute aortic dissection.

PMID- 29375233
TI  - Extremal values on Zagreb indices of trees with given distance k-domination
      number.
AB  - Let [Formula: see text] be a graph. A set [Formula: see text] is a distance k
      dominating set of G if for every vertex [Formula: see text], [Formula: see text]
      for some vertex [Formula: see text], where k is a positive integer. The distance
      k-domination number [Formula: see text] of G is the minimum cardinality among all
      distance k-dominating sets of G. The first Zagreb index of G is defined as
      [Formula: see text] and the second Zagreb index of G is [Formula: see text]. In
      this paper, we obtain the upper bounds for the Zagreb indices of n-vertex trees
      with given distance k-domination number and characterize the extremal trees,
      which generalize the results of Borovicanin and Furtula (Appl. Math. Comput.
      276:208-218, 2016). What is worth mentioning, for an n-vertex tree T, is that a
      sharp upper bound on the distance k-domination number [Formula: see text] is
      determined.

PMID- 29375234
TI  - Exact recovery of sparse multiple measurement vectors by [Formula: see text]
      minimization.
AB  - The joint sparse recovery problem is a generalization of the single measurement
      vector problem widely studied in compressed sensing. It aims to recover a set of
      jointly sparse vectors, i.e., those that have nonzero entries concentrated at a
      common location. Meanwhile [Formula: see text]-minimization subject to matrixes
      is widely used in a large number of algorithms designed for this problem, i.e.,
      [Formula: see text]-minimization [Formula: see text] Therefore the main
      contribution in this paper is two theoretical results about this technique. The
      first one is proving that in every multiple system of linear equations there
      exists a constant [Formula: see text] such that the original unique sparse
      solution also can be recovered from a minimization in [Formula: see text] quasi
      norm subject to matrixes whenever [Formula: see text]. The other one is showing
      an analytic expression of such [Formula: see text]. Finally, we display the
      results of one example to confirm the validity of our conclusions, and we use
      some numerical experiments to show that we increase the efficiency of these
      algorithms designed for [Formula: see text]-minimization by using our results.

PMID- 29375235
TI  - Bounds for the M-spectral radius of a fourth-order partially symmetric tensor.
AB  - M-eigenvalues of fourth-order partially symmetric tensors play an important role
      in many real fields such as quantum entanglement and nonlinear elastic materials
      analysis. In this paper, we give two bounds for the maximal absolute value of all
      the M-eigenvalues (called the M-spectral radius) of a fourth-order partially
      symmetric tensor and discuss the relation of them. A numerical example is given
      to explain the proposed results.

PMID- 29375236
TI  - Discussion of some inequalities via fractional integrals.
AB  - Recently, many generalizations and extensions of well-known inequalities were
      obtained via different kinds of fractional integrals. In this paper, we show that
      most of those results are particular cases of (or equivalent to) existing
      inequalities from the literature. As consequence, such results are not real
      generalizations.

PMID- 29375237
TI  - New verifiable stationarity concepts for a class of mathematical programs with
      disjunctive constraints.
AB  - In this paper, we consider a sufficiently broad class of non-linear mathematical
      programs with disjunctive constraints, which, e.g. include mathematical programs
      with complemetarity/vanishing constraints. We present an extension of the concept
      of [Formula: see text]-stationarity which can be easily combined with the well
      known notion of M-stationarity to obtain the stronger property of so-called
      [Formula: see text]-stationarity. We show how the property of [Formula: see text]
      stationarity (and thus also of M-stationarity) can be efficiently verified for
      the considered problem class by computing [Formula: see text]-stationary
      solutions of a certain quadratic program. We consider further the situation that
      the point which is to be tested for [Formula: see text]-stationarity, is not
      known exactly, but is approximated by some convergent sequence, as it is usually
      the case when applying some numerical method.

PMID- 29375238
TI  - Monosubstituted Phenylboronic Acids, R-B(OH)2 (R = C6H5, C6H4CH3, C6H4NH2,
      C6H4OH, and C6H4F): A Computational Investigation.
AB  - Phenylboronic acids (PBAs) are an important class of compounds with diverse
      applications in synthetic, biological, medicinal, and materials chemistry. In
      this investigation we report structural and thermochemical parameters for several
      monosubstituted ortho, meta, and para PBAs, R-B(OH)2 (R = C6H5, C6H4CH3, C6H4NH2,
      C6H4OH, and C6H4F). Equilibrium geometries of all the PBAs discussed in this
      article were obtained using second-order Moller-Plesset perturbation theory (MP2)
      with the Dunning-Woon aug-cc-pVDZ basis set; heats of formation (HOF) were
      calculated at the Gaussian-3 (G3) level of theory. The endo-exo conformers of all
      the positional isomers of these PBAs were lowest in energy. Using HOF for the
      monosubstituted PBAs calculated at the G3 level of theory, in conjunction with
      the experimental HOF for benzene, toluene, aniline, phenol, and fluorobenzene,
      the values of [Formula: see text] for the transfer processes C6H6 + C6H4X-B(OH)2 
      > C6H5X + C6H5-B(OH)2 (X = CH3, NH2, OH, and F) are found to be in good agreement
      with values of [Formula: see text] calculated at the MP2(FC)/aug-cc
      pVTZ//MP2(FC)/aug-cc-pVTZ computational level; the bonding in the reactants and
      products for these transfer reactions are well-matched and thermochemical
      calculations at this level are expected to be very accurate, providing checks on
      the G3 HOF calculations.

PMID- 29375240
TI  - Learning to Compose Domain-Specific Transformations for Data Augmentation.
AB  - Data augmentation is a ubiquitous technique for increasing the size of labeled
      training sets by leveraging task-specific data transformations that preserve
      class labels. While it is often easy for domain experts to specify individual
      transformations, constructing and tuning the more sophisticated compositions
      typically needed to achieve state-of-the-art results is a time-consuming manual
      task in practice. We propose a method for automating this process by learning a
      generative sequence model over user-specified transformation functions using a
      generative adversarial approach. Our method can make use of arbitrary, non
      deterministic transformation functions, is robust to misspecified user input, and
      is trained on unlabeled data. The learned transformation model can then be used
      to perform data augmentation for any end discriminative model. In our
      experiments, we show the efficacy of our approach on both image and text
      datasets, achieving improvements of 4.0 accuracy points on CIFAR-10, 1.4 F1
      points on the ACE relation extraction task, and 3.4 accuracy points when using
      domain-specific transformation operations on a medical imaging dataset as
      compared to standard heuristic augmentation approaches.

PMID- 29375241
TI  - Barriers to Healthcare for American Indians Experiencing Homelessness.
AB  - Members of American Indian (AI) communities face many barriers to receiving both
      mental and physical healthcare. These barriers can have a negative effect on
      overall health. Barriers are compounded for AIs who are also experiencing
      homelessness, and AI make up a disproportionate percentage of the homeless
      population nationwide. In-depth semi-structured interviews were conducted with 12
      service providers and 16 homeless participants in a mid-size Midwestern city to
      identify barriers to care for homeless participants. Key barriers identified in
      this study for homeless participants were: transportation, phone accessibility,
      discrimination, and cold and bureaucratic cultures of healthcare systems. Major
      barriers identified by service providers were: access to care, discrimination and
      mistrust, and restrictive policies. Given generally higher disease prevalence
      within the homeless population and health disparities within the AI community,
      steps should be taken to reduce barriers to healthcare.

PMID- 29375239
TI  - Human Genetic Adaptation to High Altitudes: Current Status and Future Prospects.
AB  - The question of whether human populations have adapted genetically to high
      altitude has been of interest since studies began there in the early 1900s.
      Initially there was debate as to whether genetic adaptation to high altitude has
      taken place based, in part, on disciplinary orientation and the sources of
      evidence being considered. Studies centered on short-term responses, termed
      acclimatization, and the developmental changes occurring across lifetimes. A
      paradigm shift occurred with the advent of single nucleotide polymorphism (SNP)
      technologies and statistical methods for detecting evidence of natural selection,
      resulting in an exponential rise in the number of publications reporting genetic
      adaptation. Reviewed here are the various kinds of evidence by which adaptation
      to high altitude has been assessed and which have led to widespread acceptance of
      the idea that genetic adaptation to high altitude has occurred. While
      methodological and other challenges remain for determining the specific gene or
      genes involved and the physiological mechanisms by which they are exerting their
      effects, considerable progress has been realized as shown by recent studies in
      Tibetans, Andeans and Ethiopians. Further advances are anticipated with the
      advent of new statistical methods, whole-genome sequencing and other molecular
      techniques for finer-scale genetic mapping, and greater intradisciplinary and
      interdisciplinary collaboration to identify the functional consequences of the
      genes or gene regions implicated and the time scales involved.

PMID- 29375242
TI  - CFD gas distribution analysis for different continuous-miner scrubber redirection
      configurations.
AB  - The U.S. National Institute for Occupational Safety and Health (NIOSH)'s
      Pittsburgh Mining Research Division (PMRD) recently developed a series of models
      using computational fluid dynamics (CFD) to study gas distribution around a
      continuous mining machine with various fan-powered flooded bed scrubber discharge
      configurations in an exhaust curtain working face. CFD models utilizing species
      transport model without reactions in FLUENT were constructed to evaluate the
      redirection of scrubber discharge toward the mining face rather than behind the
      return curtain. The study illustrates the gas distribution in the slab (second)
      cut. The following scenarios are considered in this study: 100 percent of the
      discharge redirected back toward the face on the off-curtain side; 100 percent of
      the discharge redirected back toward the face, but divided equally to both sides;
      and 15 percent of the discharge redirected toward the face on the off-curtain
      side, with 85 percent directed toward the return curtain. These models are
      compared against a model with a conventional scrubber discharge where air is
      directed away from the face into the return. The models were validated against
      experimental data, proving to accurately predict sulfur hexafluoride (SF6) gas
      levels at four gas monitoring locations. This study includes a predictive
      simulation examining a 45 degrees  scrubber angle compared with the 23 degrees 
      angle for the 100 percent redirected, equally divided case. This paper describes
      the validation of the CFD models based on experimental data of the gas
      distribution results.

PMID- 29375243
TI  - Strategic Talk in Film.
AB  - Conversational robots and agents are being designed for educational and/or
      persuasive tasks, e.g., health or fitness coaching. To pursue such tasks over a
      long time, they will need a complex model of the strategic goal, a variety of
      strategies to implement it in interaction, and the capability of strategic talk.
      Strategic talk is incipient ongoing conversation in which at least one
      participant has the objective of changing the other participant's attitudes or
      goals. The paper is based on the observation that strategic talk can stretch over
      considerable periods of time and a number of conversational segments. Film
      dialogues are taken as a source to develop a model of the strategic talk of
      mentor characters. A corpus of film mentor utterances is annotated on the basis
      of the model, and the data are interpreted to arrive at insights into mentor
      behavior, especially into the realization and sequencing of strategies.

PMID- 29375244
TI  - Elastic Modulus of Osteoporotic Mouse Femur Based on Femoral Head Compression
      Test.
AB  - A biomechanical test is a good evaluation method that describes the structural,
      functional, and pathological differences in the bones, such as osteoporosis and
      fracture. The tensile test, compression test, and bending test are generally
      performed to evaluate the elastic modulus of the bone using mice. In particular,
      the femoral head compression test is mainly used for verifying the osteoporosis
      change of the femoral neck. This study conducted bone mineral density analysis
      using in vivo microcomputed tomography (micro-CT) to observe changes in
      osteoporosis over time. It proposed a method of identifying the elastic modulus
      of the femur in the normal group (CON group) and the osteoporotic group (OVX
      group) through finite element analysis based on the femoral head compression test
      and also conducted a comparative analysis of the results. Through the femoral
      head compression test, it was verified that the CON group's ultimate and yield
      loads were significantly higher than those of the OVX group. It was considered
      that this result was caused by the fact that the bone mineral density change by
      osteoporosis occurred in the proximal end more often than in the femur diaphysis.
      However, the elastic modulus derived from the finite element analysis showed no
      significant difference between the two groups.

PMID- 29375245
TI  - Epidemiology of Chikungunya fever outbreak in Western Jamaica during July
      December 2014.
AB  - Objective: Our study describes the 2014 Chikungunya outbreak in Western Jamaica
      in terms of geographic distribution and trend of the outbreak over time, and
      evaluates clinical symptoms of the disease based on pre-existing conditions.
      Methods: We conducted a retrospective, cross-sectional study of 609 clinically
      defined Chikungunya virus (CHIKV) fever cases that occurred in the four parishes
      of the Western Regional Health Authority of Jamaica from July 2014 to December
      2014. Cases were not confirmed by laboratory tests but met clinical and
      epidemiological criteria of CHIKV fever. Results: Our results show a propagated
      spread of CHIKV fever during the outbreak period with the peak at the end of
      October. Main urban cities, such as Montego Bay and Lucea, were identified as
      places that had high numbers of cases. Fever and arthralgia were the two most
      common clinical symptoms in CHIKV patients. Although a majority (80%) of infants
      aged <2 years had up to four symptoms (80%), the percentage of infants with
      higher numbers of symptoms (9-10) was higher than in older age groups. However,
      back pain was found to occur significantly more in older patients. Those with
      arthritis as a pre-existing condition were more likely to experience headache,
      asthenia, back pain, and periarticular edema. Conclusion: These findings can help
      public health officials develop more effective programs to prevent the spread of
      CHIKV outbreaks by focusing on crowded urban cities. The findings indicate that
      those who are likely to develop a higher number of symptoms, such as young
      infants and people with pre-existing conditions, such as arthritis, should be
      more closely monitored to better manage the disease outcome.

PMID- 29375247
TI  - 'Homework' and Transnational Adoption Screening in Spain: The Co-Production of
      Home and Family.

PMID- 29375246
TI  - Effects of Chronic Musculoskeletal Pain on Fertility Potential in Lean and
      Overweight Male Patients.
AB  - Both chronic pain and obesity are known to affect reproductive hormone profiles
      in male patients. However, the effect of these conditions, alone or in
      combination, on male fertility potential has received less attention. 20 chronic
      musculoskeletal pain patients and 20 healthy controls were divided into lean and
      overweight subgroups according to their BMI. Current level of chronic pain
      (visual analogue scale) and pressure pain thresholds (PPTs) in 16 predefined
      sites, classically described and tested as painful points on the lower body, were
      measured. Levels of reproductive hormone and lipid profiles were assessed by
      ELISA. Sperm concentration and motility parameters were analyzed using a computer
      aided sperm analysis system. Sperm concentration, progressive motility, and
      percentage of hyperactivated sperm were generally lower in the chronic pain
      patients in both lean and overweight groups. The overweight control and the lean
      chronic pain groups demonstrated a significantly lower percentage of
      progressively motile sperm compared with the lean control group, suggesting that
      musculoskeletal chronic pain may have a negative influence on sperm quality in
      lean patients. However, due to the potential great negative influence of obesity
      on the sperm parameters, it is difficult to propose if musculoskeletal chronic
      pain also influenced sperm quality in overweight patients. Further research in
      chronic pain patients is required to test this hypothesis.

PMID- 29375248
TI  - Development of an instrument to measure Faculty's information and communication
      technology access (FICTA).
AB  - The phenomenon of "digital divide" is complex and multidimensional, extending
      beyond issues of physical access. The purpose of this study was to develop a
      scale to measure a range of factors related to digital divide among higher
      education faculty and to evaluate its reliability and validity. Faculty's
      Information and Communication Technology Access (FICTA) scale was tested and
      validated with 322 faculty teaching in public and private sector universities.
      Principal components analysis with varimax rotation confirmed an 8-factor
      solution corresponding to various dimensions of ICT access. The 57-item FICTA
      scale demonstrated good psychometric properties and offers researchers a tool to
      examine faculty's access to ICT at four levels - motivational, physical, skills,
      and usage access.

PMID- 29375249
TI  - Robust estimation of encouragement-design intervention effects transported across
      sites.
AB  - We develop robust targeted maximum likelihood estimators (TMLE) for transporting
      intervention effects from one population to another. Specifically, we develop
      TMLE estimators for three transported estimands: intent-to-treat average
      treatment effect (ATE) and complier ATE, which are relevant for encouragement
      design interventions and instrumental variable analyses, and the ATE of the
      exposure on the outcome, which is applicable to any randomized or observational
      study. We demonstrate finite sample performance of these TMLE estimators using
      simulation, including in the presence of practical violations of the positivity
      assumption. We then apply these methods to the Moving to Opportunity trial, a
      multi-site, encouragement-design intervention in which families in public housing
      were randomized to receive housing vouchers and logistical support to move to low
      poverty neighborhoods. This application sheds light on whether effect differences
      across sites can be explained by differences in population composition.

PMID- 29375250
TI  - Alexithymia, Defenses, and Ego Strength: Cross-sectional and Longitudinal
      Relationships with Psychological Well-Being and Depression.
AB  - Affect regulation is important to mental health. A deficit in one's ability to
      identify and express emotions (alexithymia), cognitive styles of regulating
      emotional conflict (defenses), and the capacity for integrative and complex self
      other understanding (ego strength or maturity) need to be studied to understand
      how they relate to each other as well as to mental health and well-being. A
      sample of 415 community-dwelling adults from a major metropolitan area in the
      Midwest U.S., stratified for gender, age, and ethnicity, completed three
      methodologically different measures of affect regulation along with measures of
      well-being and depression. Six years later, 49% of the sample again reported
      their well-being and depression. At baseline, ego strength and the defenses of
      principalization and reversal correlated negatively with alexithymia and the
      other defenses (turning against self, turning against object and projection),
      even after controlling for negative affect. Cross-sectionally, relationships were
      largely as hypothesized, with low alexithymia, use of mature defenses, and
      greater ego strength correlating with less depression and greater well-being,
      although some of these relationships were attenuated after controlling for
      negative affect. Prospectively, each of the affect regulation measures predicted
      hypothesized changes in well-being after 6 years, after controlling for baseline
      well-being, but affect regulation did not predict changes in depression. These
      findings illuminate similarities and differences among these affect regulation
      constructs, suggest the importance of differentiating well-being from depression,
      and reveal that affect regulation uniquely predicts changes in long-term well
      being.

PMID- 29375251
TI  - Associated factors to the adults older than 50 years corresidence by rural-urban
      condition.
AB  - Based on the information generated by the National Census of Health and Aging in
      Mexico (Enasem, 2001), the following article analyzes the influence of some
      demographic, socioeconomic and health variables in the residential arrangements
      of adults older than 50 years of age in Mexico. Using descriptive statistics and
      parting from the construction of two m-logit models, it is found that most of the
      people of more than 50 years share dwelling with their children, particularly the
      single ones. The coresidence with married children occurs with more frequency
      when seniors do not have couple and present functional deterioration.

PMID- 29375252
TI  - PROGNOSTIC FACTORS IN PATIENTS WITH PRESSURE SORES IN A UNIVERSITY HOSPITAL IN
      SOUTHERN BRAZIL.
AB  - Objective: Despite advances in medical care, patients who are hospitalized or
      have spinal cord injuries often develop pressure sores. The objective of this
      study was to describe the epidemiological characteristics of pressure sores and
      evaluate factors associated with recurrence and cure. Methods: In this historical
      cohort study, clinical and laboratory data were collected from medical records
      between 1997 and 2016. Results: Sixty individuals with pressure ulcers were
      included; mean patient age was 38.1+/-16.5 (37.0) years, 83.3% were men, and
      86.8% identified as white. Most patients (85.1%) had paraplegia, amputation, or
      trauma of the lower limbs with motor sequelae; the remainder (14.9%) were
      quadriplegic. Most (78.3%) underwent surgery, and the mean follow-up time was
      1.8+/-2.5 years. The lesions were cured in 25 patients; they recurred in 25% of
      the patients, and recurrence was seen to be associated with the location of the
      lesions. Patients with recurrent lesions had more medical consultations and a
      longer treatment time. Individuals whose ulcers had healed had fewer lesions,
      higher body mass index (BMI), and a higher proportion of these patients underwent
      surgery. Conclusions: BMI and location and number of lesions are prognostic
      factors. Level of Evidence IV, Case Series.

PMID- 29375253
TI  - EVALUATION OF FUNCTIONAL CHARACTERISTICS IN PATIENTS WITH KNEE OSTEOARTHRITIS.
AB  - Objective: This study evaluated the physical and functional characteristics of
      Turkish patients with knee osteoarthritis and how this disease affects their
      physical and functional status. Methods: This study included 320 patients, who
      were evaluated to assess body mass index (BMI) and Hospital for Special Surgery
      (HSS) score in terms of age, sex and functional characteristics. Results: Mean
      patient age was 66.92+/-8.89 years and mean BMI was 31.02+/-5.20 kg/m2. Mean
      patient HSS score was 58.70+/-11.08. According to their sit-to-stand test
      results, 33% of the patients (n=104) were found to be independent. There was a
      significant relationship between BMI and functional activity score (p<0.05).
      Conclusions: The majority of the patients in our study were female and obese, and
      had low functionality levels. Function in patients with OA is restricted as a
      result of excess weight, so preventive measures can help Turkish patients with OA
      maintain their ideal weight. Furthermore, patient education can be help this
      population acquire the habit of regular exercise in order to reduce pain and
      improve their physical activity and quality of life. Level of Evidence IV, Case
      Series.

PMID- 29375254
TI  - LATE EVALUATION OF PATIENTS UNDERGOING MANIPULATION OF THE KNEE AFTER TOTAL
      ARTHROPLASTY.
AB  - Objective: We compared gains in range of motion in patients who underwent
      manipulation within 12 weeks of total knee arthroplasty (TKA) and after this
      period. We also evaluated maintenance of the arc obtained from knee manipulation
      in late follow-up, along with factors associated with poorer outcomes. Method:
      The study was divided into two groups according to the time after TKA; the
      surgeries took place between January 2008 and December 2014. Results: When
      comparing the range of motion between early and late manipulations, the group
      that underwent manipulation within 12 weeks of the TKA exhibited better outcomes,
      but these were not statistically significant. We observed that 14.3% of cases
      retained the same range attained at the time of manipulation. In late evaluation
      after manipulation, 47.7% of the sample had a range of less than 90 degrees. The
      significant risk factors for recurrence of knee stiffness in the long term are
      poor range of motion before TKA and before manipulation, female sex, and
      secondary arthritis. Conclusion: Women previously diagnosed with secondary
      osteoarthritis and poor range of motion before TKA or manipulation are at higher
      risk for late stiffness. Level of Evidence III, Retrospective Comparative Study.

PMID- 29375255
TI  - MAXILLOFACIAL TRAUMA, ETIOLOGY AND PROFILE OF PATIENTS: AN EXPLORATORY STUDY.
AB  - Objective: To describe the profile of patients with facial trauma admitted in a
      hospital located in a metropolitan area of Northeast Brazil. Methods: A cross
      sectional and exploratory study was performed. A total of 244 cases were in
      agreement with the eligibility criteria. The variables include the
      sociodemographic characteristics of patients, etiology, type of trauma, treatment
      modalities, length of stay in a hospital and quarter of care. Descriptive
      statistics and Cluster Analysis were performed. Results: The average age of
      patients was 31.16 years (SD = 15.17 years) and average hospitalization was 6.32
      days (SD = 7.75 days). It was verified the automatic formation of four clusters
      with different profiles of patients. The variables which most contributed to the
      external differentiation between clusters were: length of stay in a hospital (p
      <0.001), etiology (p <0.001), type of facial trauma (p <0.001), presence of
      associated trauma (p <0.001), treatment modalities (p <0.001) and quarter of care
      (p <0.001). Conclusion: The most of patients were men, victims of traffic
      accidents, which suffered fracture of zygomatic complex and underwent surgery.
      Level of Evidence III, Retrospective Study.

PMID- 29375256
TI  - PREVALENCE OF OSTEOPOROSIS AND HYPOVITAMINOSIS D AT SIRIRAJ METABOLIC BONE
      DISEASE CLINIC.
AB  - Objective: To identify the prevalence of osteoporosis and hypovitaminosis D among
      patients at the Siriraj Metabolic Bone Disease (MBD) Clinic, and to compare
      initial vitamin D levels in patients with and without a history of fragility
      fractures. Methods: Medical records of patients who attended our MBD clinic
      between 2012 and 2015 were retrospectively reviewed. Patient baseline
      demographic, clinical, bone mineral density (BMD), and laboratory data were
      collected and analyzed. Osteoporosis was diagnosed when patients had a BMD T
      score <-2.5 or presented with fragility fractures. Results: There were 761
      patients included in this study. Of these, 627 patients (82.4%) were diagnosed
      with osteoporosis and 508 patients (66.8%) had fragility fractures. Baseline
      serum 25-hydroxyvitamin D (25(OH)D) levels were available in 685 patients. Of
      these, 391 patients (57.1%) were diagnosed with hypovitaminosis D. When evaluated
      only in patients with fragility fractures, the average initial 25(OH)D level was
      28.2+/-11.6 ng/mL, and the prevalence of hypovitaminosis D was 57.6%. Conclusion:
      A high prevalence of osteoporosis and hypovitaminosis D was found among patients
      at our clinic; two-thirds of patients had a history of fragility fractures, and
      no difference in initial 25(OH)D levels was seen between patients with and
      without fragility fractures. Level ofEvidence III, Retrospective Study.

PMID- 29375257
TI  - EVALUATION OF SURGICAL TREATMENT OF PATIENTS WITH SHOULDER INSTABILITY.
AB  - Objective: To evaluate the results of arthroscopic surgery in patients with
      traumatic anterior shoulder dislocation. Methods: This retrospective study
      analyzed 76 patients with a mean age of 28 and mean postoperative follow-up
      period of 62 months. Evaluation consisted of physical examination, and X-rays;
      results were classified according to the UCLA and Rowe scales. Results: Patients
      showed decrease of range of motion in all planes, except elevation and lateral
      rotation with 90o abduction. According to the Rowe score, significant
      postoperative improvement was found compared with preoperative evaluations, with
      89.4% of satisfactory results. According to the UCLA score, good or excellent
      results were observed in 97.4% of the cases. We found a 6.5% rate of recurrence.
      Conclusion: Arthroscopic treatment for traumatic anterior shoulder dislocation is
      effective, as long as indications are used. Level of Evidence IV, Case Series.

PMID- 29375258
TI  - MID-LONG TERM RESULTS OF MANIPULATION AND ARTHROSCOPIC RELEASE IN FROZEN
      SHOULDER.
AB  - Objective: Surgical treatment options should be discussed in cases of frozen
      shoulder, which is usually treated in a conservative manner. In this study, we
      evaluated the efficacy of manipulation and arthroscopic release in cases of
      frozen shoulder which resisted conservative treatment. Methods: A total of 32
      patients who underwent manipulation and arthroscopic capsular release in 34
      shoulders were included in the study. The average follow-up period was 49.5
      months (range: 24-90 months). No reason for onset could be found in 8 (25%)
      patients, who were classified as primary frozen shoulder; twenty-four (75%)
      patients were classified as secondary frozen shoulder due to underlying
      pathologies. The average pre-operative complaint period was 11 months (range: 3
      24 months). After arthroscopic examination, manipulation was performed first,
      followed by arthroscopic capsular release. The range of motion in both shoulders
      was compared before the procedure and in the last follow-up visit. Constant and
      Oxford classifications were used to assess functional results, and the results
      were assessed statistically. Results: Patient values for passive elevation,
      abduction, adduction-external rotation, abduction-external rotation, and
      abduction-internal rotation increased in a statistically significant manner
      between the preoperative assessment and follow-up evaluation (p<0.01). The
      average change of 47.97+/-21.03 units observed in the patients' values obtained
      in the control measurements against the pre-op Constant scores was determined to
      be statistically significant (p<0.01). According to the Oxford classification, 29
      shoulders were sufficient. Conclusion: Successful results can be obtained with
      arthroscopic release performed after manipulation in patients with frozen
      shoulder resistant to conservative treatment. Level of Evidence IV, Case Series.

PMID- 29375259
TI  - QUALITY OF LIFE IN PATIENTS WITH ROTATOR CUFF ARTHROPATHY.
AB  - Objective: To compare quality of life (according to the SF-12) in patients with
      rotator cuff arthropathy with controls paired by sex and age. Secondary
      objectives are to compare the groups according to the ASES and VAS scales.
      Methods: This cross-sectional study with controls paired by sex and age compared
      patients with rotator cuff arthropathy with surgical indication for reverse
      shoulder arthroplasty. The groups were compared according to the SF-12, ASES, and
      VAS scales. Results: The groups consisted of 38 individuals, 28 women. The SF-12
      demonstrated a significant difference in the physical component, with the cases
      scoring 31.61 +/- 6.15 and the controls 49.39 +/- 6.37 (p<0.001). For the mental
      component, the difference was not significant, with the cases scoring 44.82 +/-
      13.18 and the controls 48.96 +/- 8.65 (p=0.109). The cases scored 7.34 +/- 2.11
      on the VAS and 31.26 +/- 15.12 on the ASES, while the controls scored 0.55 +/-
      1.31 and 97.53 +/- 6.22, respectively (p<0.001). Conclusion: Patients with
      rotator cuff arthropathy had poorer results for the physical component of the SF
      12 than the controls. They also had poorer functional results according to the
      ASES scale, and more pain according to the VAS. Level of Evidence III, Case
      Control Study.

PMID- 29375260
TI  - STUDY OF SECONDARY OSSIFICATION CENTERS OF THE ELBOW IN THE BRAZILIAN POPULATION.
AB  - Objective: To evaluate the age in which the secondary ossification centers of the
      elbow appear and fuse in the Brazilian population. Methods: Nearly thirty
      radiographs were randomly selected for each age group from 0 to 18 years, with a
      total of 544 radiographs from 439 patients, between 2010 and 2015, without
      abnormalities secondary to trauma, metabolic or bone tumor diseases. Radiographs
      were retrospectively evaluated by two blind and independent observers, according
      to the presence or not of the ossification centers, and the fusion between them.
      Results: The age interval of appearance and fusion were, respectively: capitulum
      (0 to 1 year; 10 to 15 years), radius head (2 to 6 year; 12 to 16 years), medial
      epicondyle (2 to 8 years; 13 to 17 years), trochlea (5 to 11 years; 10 to 18
      years), olecranon (6 to 11 years; 13 to 16 years), e lateral epicondyle (8 to 13
      years; 12 to 16 years). Appearance and fusion were earlier in girls compared to
      boys (exception to capitulum and radius head). Conclusion: The chronological
      order was similar to the literature. For girls, the radius head and medial
      epicondyle appeared simultaneously. There was a tendency of the olecranon center
      to appear before the trochlea for both sexes. Level of Evidence III, Diagnostic
      Study.

PMID- 29375261
TI  - TERRIBLE TRIAD OF THE ELBOW: FUNCTIONAL RESULTS OF SURGICAL TREATMENT.
AB  - Objective: To evaluate the functional and radiographic results of patients who
      underwent surgical treatment for terrible triad-type elbow injuries (TTE).
      Methods: We retrospectively evaluated 20 patients, including one case with
      bilateral injuries (total of 21 elbows) that were surgically treated from January
      2004 to July 2014. We evaluated the functional results of treatment by measuring
      the restored range of motion (ROM) of the elbow, using the DASH (Disabilities of
      the Arm, Shoulder and Hand) and MEPS (Mayo Elbow Performance Score) scores.
      Complications and the development of osteoarthritis and heterotopic ossification
      (HO) were also evaluated. Results: Eight elbows (38%) required additional
      surgical treatment; HO was observed in eight elbows (38%) and severe
      osteoarthritis (Broberg-Morrey type IV) was seen in only one case (4%).
      Nevertheless, we obtained good functional results, 14.27 on the DASH and 84 on
      the MEPS. The average ROM for flexion-extension was 101 degrees  (20-140 degrees
      ) and for pronation-supination was 112.85 degrees  (0-180 degrees ). Conclusion:
      When TTE injuries are treated systematically, even despite variations in these
      injuries, functional ROM and scores ranging from good to excellent can be
      obtained. Level of Evidence IV, Case Series.

PMID- 29375262
TI  - INCIDENCE OF ACUTE TRAUMA ON HAND AND WRIST: A RETROSPECTIVE STUDY.
AB  - Objectives: A retrospective statistical data gathering of wrist and hand
      complaints assisted over two years in the orthopedic emergency department of a
      regional referral hospital, seeking to know the profile of these patients.
      Methods: Information obtained by analysis of 31.356 orthopedic visits from May
      2013 to April 2015, of which 6.754 related to hand complaints and/or wrist, at
      the Hospital Estadual Doutor Jayme dos Santos Neves (HDJSN) and analyzed by IBM
      SPSS Statistics software version 21. Results: The data revealed that the average
      age was 37,5 +/- 15,7 years and the male gender was predominant (60,72%). Bruises
      (52,58%) and fractures (30,49%) were the most common diagnoses. Conclusion: The
      complaints of wrist and hand accounted for 21,44% of all orthopedic emergency
      room visits. Detailed data description and correct definition of the
      International Classification of Diseases (ICD-10) are needed to better define the
      epidemiological profile of patients seeking orthopedic emergency. Level of
      Evidence III, Retrospective Study.

PMID- 29375264
TI  - ERRATA.
AB  - [This corrects the article DOI: 10.1590/1413-785220172504167561.].

PMID- 29375263
TI  - WRIST ARTHROSCOPY: BASIC TIPS FOR DRY ARTHROSCOPIC EXPLORATION.
AB  - Objective: This article provides details and tips on the dry arthroscopic
      technique, based on our experience and its clinical applications. Method: The
      technique was applied to 65 patients (33 men and 32 women) aged between 20 and 62
      years (average of 35.4 years) for treating: synovial cyst resection, scapholunate
      ligament injury repair, ulnocarpal impact correction, triangular fibrocartilage
      injury repair, and assisted reduction of distal radius fractures. Results: A
      minimally invasive intra-articular evaluation has been observed as a benefit,
      with low infection rate, small scars, and high rates of early recovery, without
      affecting intra-articular fluid use, reducing the risk of compartment syndrome
      and infiltrated soft tissues, in the case of need for associated open surgery. As
      for the difficulties, we report the surgeon's view, which is commonly prevented
      by optical blurring or debris that hit the lens, and the need for radiofrequency
      care, since the heat generated is dissipated with greater difficulty than in the
      classical technique. Conclusion: Dry arthroscopy emerges as an effective choice
      to treat wrist pathologies, however, deep knowledge and ease with the classical
      technique, as well as a learning curve, are key to obtain a good outcome. Level
      of Evidence V, Expert Opinion.

PMID- 29375265
TI  - Measuring inefficiency for specific inputs using data envelopment analysis:
      evidence from construction industry in Spain and Portugal.
AB  - This article contributes to the efficiency literature by defining, in the context
      of the data envelopment analysis framework, the directional distance function
      approach for measuring both technical and scale inefficiencies with regard to the
      use of individual inputs. The input-specific technical and scale inefficiencies
      are then aggregated in order to calculate the overall inefficiency measures.
      Empirical application focuses on a large dataset of Spanish and Portuguese
      construction companies between 2002 and 2010 and accounts for three inputs:
      materials, labor and fixed assets. The results show, first, that for both Spanish
      and Portuguese construction companies, fixed assets are the most technically
      inefficient input. Second, the most inefficient scale concerns the utilization of
      material input in both samples; the reason for this inefficiency is that firms
      tend to operate in the increasing returns to scale portion of technology set.
      Third, in both samples, large firms have the lowest input-specific technical
      inefficiencies, but the highest input-specific scale inefficiencies, compared to
      their small and medium-sized counterparts, and tend to suffer from decreasing
      returns to scale. Finally, in both samples, input-specific technical inefficiency
      under constant returns to scale increased during the period of the recent
      financial crisis, mainly due to the augmentation in scale inefficiency.

PMID- 29375266
TI  - A framework for sensitivity analysis of decision trees.
AB  - In the paper, we consider sequential decision problems with uncertainty,
      represented as decision trees. Sensitivity analysis is always a crucial element
      of decision making and in decision trees it often focuses on probabilities. In
      the stochastic model considered, the user often has only limited information
      about the true values of probabilities. We develop a framework for performing
      sensitivity analysis of optimal strategies accounting for this distributional
      uncertainty. We design this robust optimization approach in an intuitive and not
      overly technical way, to make it simple to apply in daily managerial practice.
      The proposed framework allows for (1) analysis of the stability of the expected
      value-maximizing strategy and (2) identification of strategies which are robust
      with respect to pessimistic/optimistic/mode-favoring perturbations of
      probabilities. We verify the properties of our approach in two cases: (a)
      probabilities in a tree are the primitives of the model and can be modified
      independently; (b) probabilities in a tree reflect some underlying, structural
      probabilities, and are interrelated. We provide a free software tool implementing
      the methods described.

PMID- 29375268
TI  - Heuristic algorithms for the minmax regret flow-shop problem with interval
      processing times.
AB  - An uncertain version of the permutation flow-shop with unlimited buffers and the
      makespan as a criterion is considered. The investigated parametric uncertainty is
      represented by given interval-valued processing times. The maximum regret is used
      for the evaluation of uncertainty. Consequently, the minmax regret discrete
      optimization problem is solved. Due to its high complexity, two relaxations are
      applied to simplify the optimization procedure. First of all, a greedy procedure
      is used for calculating the criterion's value, as such calculation is NP-hard
      problem itself. Moreover, the lower bound is used instead of solving the internal
      deterministic flow-shop. The constructive heuristic algorithm is applied for the
      relaxed optimization problem. The algorithm is compared with previously
      elaborated other heuristic algorithms basing on the evolutionary and the middle
      interval approaches. The conducted computational experiments showed the advantage
      of the constructive heuristic algorithm with regards to both the criterion and
      the time of computations. The Wilcoxon paired-rank statistical test confirmed
      this conclusion.

PMID- 29375267
TI  - Tight upper bounds for semi-online scheduling on two uniform machines with known
      optimum.
AB  - We consider a semi-online version of the problem of scheduling a sequence of jobs
      of different lengths on two uniform machines with given speeds 1 and s. Jobs are
      revealed one by one (the assignment of a job has to be done before the next job
      is revealed), and the objective is to minimize the makespan. In the considered
      variant the optimal offline makespan is known in advance. The most studied
      question for this online-type problem is to determine the optimal competitive
      ratio, that is, the worst-case ratio of the solution given by an algorithm in
      comparison to the optimal offline solution. In this paper, we make a further step
      towards completing the answer to this question by determining the optimal
      competitive ratio for s between [Formula: see text] and [Formula: see text], one
      of the intervals that were still open. Namely, we present and analyze a compound
      algorithm achieving the previously known lower bounds.

PMID- 29375269
TI  - Racial segregation in postbellum Southern cities: The case of Washington, D.C.
AB  - BACKGROUND: Segregation in Southern cities has been described as a 20th-century
      development, layered onto an earlier pattern in which whites and blacks (both
      slaves and free black people) shared the same neighborhoods. Urban historians
      have pointed out ways in which the Southern postbellum pattern was less benign,
      but studies relying on census data aggregated by administrative areas - and
      segregation measures based on this data - have not confirmed their observations.
      METHODS: This study is based mainly on 100% microdata from the 1880 census that
      has been mapped at the address level in Washington, D.C. This data makes it
      possible to examine in detail the unique spatial configuration of segregation
      that is found in this city, especially the pattern of housing in alleys. RESULTS:
      While segregation appears to have been low, as reflected in data by wards and
      even by much smaller enumeration districts, analyses at a finer spatial scale
      reveal strongly patterned separation between blacks and whites at this early
      time. CONTRIBUTION: This research provides much new information about segregation
      in a major Southern city at the end of the 19th century. It also demonstrates the
      importance of dealing explicitly with issues of both scale and spatial pattern in
      studies of segregation.

PMID- 29375270
TI  - The body in Martin Amis's Experience (2000).
AB  - This paper focuses on the presentation of the body in Martin Amis's memoir
      Experience (2000) and compares Amis's account of the growth of his mind and body
      with ideas put forward by writers in the phenomenological and psychoanalytic
      traditions. Using the ideas of body schema, projective identification and idea of
      safety, it advances a new conceptual framework for the thinking about the
      contribution that the body makes to selfhood in autobiography.

PMID- 29375271
TI  - MicroRNA-10b regulates epithelial-mesenchymal transition by modulating
      KLF4/KLF11/Smads in hepatocellular carcinoma.
AB  - Background: Our previous work showed that miR-10b was overexpressed in
      hepatocellular carcinoma (HCC) and promoted HCC cell migration and invasion.
      Epithelial-mesenchymal transition (EMT) is involved in HCC metastasis. So, we
      suspected that miR-10b might participate in the HCC EMT. Methods: We performed
      morphological analysis and immunofluorescence to observe the roles of miR-10b in
      HCC EMT. The expression of KLF11 and EMT markers were detected by real-time RT
      PCR and western blot. The regulation roles of miR-10b on KLF11 and KLF4 were
      determined by luciferase reporter assay. The chromatin immunoprecipitation
      revealed the binding relationship between KLF4 and KLF11. Results: We found that
      overexpression of miR-10b could promote HCC EMT. miR-10b could upregulated KLF11
      expression. The upregulation of KLF11 reduced the downstream molecular Smad7
      expression, which upregulated the Smad3 expression to promote EMT development.
      Furthermore, the induction role of miR-10b in HCC EMT could be blocked by KLF11
      siRNA. But our results showed that there was no direct regulation of miR-10b in
      KLF11 expression. Specifically, miR-10b could bind to the 3'UTR of KLF4 and
      inhibit KLF4 expression. KLF4 could directly bind to KLF11 promoter and
      downregulate KLF11 transcription. Conclusion: Our results reveal that miR-10b
      downregulates KLF4, the inhibitory transcriptional factor of KLF11, which induces
      Smads signaling activity to promote HCC EMT. Our study presents the regulation
      mechanism of miR-10b in EMT through the KLF4/KLF11/Smads pathway for the first
      time and implicates miR-10b as a potential target for HCC therapies.

PMID- 29375272
TI  - A 13-year real-life study on efficacy, safety and biological effects of Vespula
      venom immunotherapy.
AB  - Background: Hymenoptera venom immunotherapy (VIT) is a clinically effective
      treatment. However, little is known about its long-term clinical efficacy and
      biological effects. Several mechanisms have been proposed to account for VIT
      efficacy, including reduction of specific IgE and induction of allergen-specific
      IgG4, but the overall picture remains elusive. We investigated Vespula VIT
      clinical efficacy up to 8 years after discontinuation and the kinetics of Vespula
      specific IgE and IgG4. Out of 686 consecutive patients we retrospectively
      selected and analysed a series of 23 patients with Vespula allergy that underwent
      a 5-year IT course, followed by a prolonged follow-up. Methods: Clinical efficacy
      of VIT was assessed as number and severity of reactions to Vespula re-stinging
      events. The presence of Vespula-specific IgE and IgG4 was also monitored over
      time. Results: During the VIT treatment, patients were protected, reporting no
      reactions or mild reactions in occasion of re-stinging events. This protection
      was entirely maintained during the follow-up, up to 8 years. Skin reactivity
      (reflecting mast cell-bound Vespula-specific IgE) and circulating Vespula
      specific IgE levels declined substantially during VIT. Notably, this reduction
      was maintained over time during the follow-up. Moreover, all the patients were
      analysed for IgG4. A robust induction of Vespula-specific IgG4 was observed
      during the VIT course, with a substantial decline during the follow-up.
      Conclusions: We conclude that Vespula VIT is a clinically effective treatment,
      which induces long-term protection after discontinuation. The reduction of
      specific IgE, assessed by skin tests and RAST, closely matches the VIT- induced
      protection, while the IgG4 induction seems not to be associated with VIT clinical
      efficacy in the long term.

PMID- 29375273
TI  - Proteomic identification of moesin upon exposure to acrolein.
AB  - Background: Acrolein (allyl Aldehyde) as one of smoke irritant exacerbates
      chronic airway diseases and increased in sputum of patients with asthma and
      chronic obstructive lung disease. But underlying mechanism remains unresolved.
      The aim of study was to identify protein expression in human lung microvascular
      endothelial cells (HMVEC-L) exposed to acrolein. Methods: A proteomic approach
      was used to determine the different expression of proteins at 8 h and 24 h after
      treatment of acrolein 30 nM and 300 nM to HMVEC-L. Treatment of HMVEC-L with
      acrolein 30 nM and 300 nM altered 21 protein spots on the two-dimensional gel,
      and these were then analyzed by MALDI-TOF MS. Results: These proteins included
      antioxidant, signal transduction, cytoskeleton, protein transduction, catalytic
      reduction. The proteins were classified into four groups according to the time
      course of their expression patterns such as continually increasing, transient
      increasing, transient decreasing, and continually decreasing. For validation
      immunohistochemical staining and Western blotting was performed on lung tissues
      from acrolein exposed mice. Moesin was expressed in endothelium, epithelium, and
      inflammatory cells and increased in lung tissues of acrolein exposed mice
      compared with sham treated mice. Conclusions: These results indicate that some of
      proteins may be an important role for airway disease exacerbation caused by
      acrolein exposure.

PMID- 29375275
TI  - Gibson Deletion: a novel application of isothermal in vitro recombination.
AB  - Background: Recombinant DNA technology is today a fundamental tool for virtually
      all biological research fields. Among the many techniques available for the
      construction of a "custom DNA" molecule, the isothermal in vitro assembly, or
      Gibson assembly, allows for an efficient, one-step, scarless recombination-based
      assembly. Results: Here, we apply and characterize the use of Gibson assembly for
      the deletion of DNA sequences around a DNA cut. This method, that we named
      "Gibson Deletion", can be used to easily substitute or delete one or more
      restriction sites within a DNA molecule. We show that Gibson Deletion is a viable
      method to delete up to 100 nucleotides from the DNA ends of a cleavage site. In
      addition, we found that Gibson Deletion can be performed using single strand DNA
      with the same efficiency as using double strand DNA molecules. Conclusions:
      Gibson Deletion is a novel, easy and convenient application of isothermal in
      vitro assembly, that performs with high efficiency and can be implemented for a
      broad range of applications.

PMID- 29375274
TI  - The diagnosis and treatment of venous thromboembolism in asian patients.
AB  - Although the incidence of venous thromboembolism (VTE) in Asian populations is
      lower than in Western countries, the overall burden of VTE in Asia has been
      considerably underestimated. Factors that may explain the lower prevalence of VTE
      in Asian populations relative to Western populations include the limited
      availability of epidemiological data in Asia, ethnic differences in the genetic
      predisposition to VTE, underdiagnoses, low awareness toward thrombotic disease,
      and possibly less symptomatic VTE in Asian patients. The clinical assessment,
      diagnostic testing, and therapeutic considerations for VTE are, in general, the
      same in Asian populations as they are in Western populations. The management of
      VTE is based upon balancing the treatment benefits against the risk of bleeding.
      This is an especially important consideration for Asian populations because of
      increased risk of intracranial hemorrhage with vitamin K antagonists. Non-vitamin
      K antagonist oral anticoagulants have shown advantages over current treatment
      modalities with respect to bleeding outcomes in major phase 3 clinical trials,
      including in Asian populations. Although anticoagulant therapy has been shown to
      reduce the risk of postoperative VTE in Western populations, VTE prophylaxis is
      not administered routinely in Asian countries. Despite advances in the management
      of VTE, data in Asian populations on the incidence, prevalence, recurrence, risk
      factors, and management of bleeding complications are limited and there is need
      for increased awareness. To that end, this review summarizes the available data
      on the epidemiology, risk stratification, diagnosis, and treatment considerations
      in the management of VTE in Asia.

PMID- 29375276
TI  - Multiple Coordination Patterns in Infant and Adult Vocalizations.
AB  - The study of vocal coordination between infants and adults has led to important
      insights into the development of social, cognitive, emotional and linguistic
      abilities. We used an automatic system to identify vocalizations produced by
      infants and adults over the course of the day for fifteen infants studied
      longitudinally during the first two years of life. We measured three different
      types of vocal coordination: coincidence-based, rate-based, and cluster-based.
      Coincidence-based and rate-based coordination are established measures in the
      developmental literature. Cluster-based coordination is new and measures the
      strength of matching in the degree to which vocalization events occur in
      hierarchically nested clusters. We investigated whether various coordination
      patterns differ as a function of vocalization type, whether different
      coordination patterns provide unique information about the dynamics of vocal
      interaction, and how the various coordination patterns each relate to infant age.
      All vocal coordination patterns displayed greater coordination for infant speech
      related vocalizations, adults adapted the hierarchical clustering of their
      vocalizations to match that of infants, and each of the three coordination
      patterns had unique associations with infant age. Altogether, our results
      indicate that vocal coordination between infants and adults is multifaceted,
      suggesting a complex relationship between vocal coordination and the development
      of vocal communication.

PMID- 29375277
TI  - Wearable Biosensors to Evaluate Recurrent Opioid Toxicity After Naloxone
      Administration: A Hilbert Transform Approach.
AB  - Opioid abuse is a rapidly escalating problem in the United States. Effective
      opioid reversal is achieved with the antidote naloxone, but often does not last
      as long as the offending opioid, necessitating in-hospital observation.
      Continuous physiologic monitoring using wearable biosensors represents a
      potential option to extend monitoring capability outside the clinical setting
      across the spectrum of opioid abuse including post- naloxone administration. The
      present study aims to identify the physiologic change that marks the cessation of
      naloxone's effect. Eleven participants were recruited in the Emergency Department
      after naloxone administration for an opioid overdose and continuously monitored
      using a wearable biosensor measuring heart rate, temperature, electrodermal
      activity and accelerometry. Hilbert transform was used to evaluate a 90- minute
      post naloxone time point. Physiologic changes were consistent with the onset of
      opioid drug effect across parameters, but only changes in heart rate and skin
      temperature research statistical significance.

PMID- 29375278
TI  - Acceptance Angle Control for Improved Transmission Imaging in an SEM.
AB  - This contribution presents a simple, cost-effective modular aperture system
      enabling comprehensive acceptance angle control for STEM-in-SEM imaging. The
      system is briefly described, and different ways to use it are explained. To
      demonstrate the utility of the approach, a few samples are examined using the new
      system with comparisons to images from traditional SEM detectors. We show that
      the system enables conventional STEM imaging modes ranging from brightfield to
      high-angle annular darkfield (that is, Z-contrast), thin annular detection
      schemes, and even some non-conventional imaging modes.

PMID- 29375279
TI  - Force Tracking with Feed-Forward Motion Estimation for Beating Heart Surgery.
AB  - The manipulation of fast moving, delicate tissues in beating heart procedures
      presents a considerable challenge to the surgeon. A robotic force tracking system
      can assist the surgeon by applying precise contact forces to the beating heart
      during surgical manipulation. Standard force control approaches cannot safely
      attain the required bandwidth for this application due to vibratory modes within
      the robot structure. These vibrations are a limitation even for single degree of
      freedom systems driving long surgical instruments. These bandwidth limitations
      can be overcome by incorporating feed-forward motion terms in the control law.
      For intracardiac procedures, the required motion estimates can be derived from 3D
      ultrasound imaging. Dynamic analysis shows that a force controller with feed
      forward motion terms can provide safe and accurate force tracking for contact
      with structures within the beating heart. In vivo validation confirms that this
      approach confers a 50% reduction in force fluctuations when compared to a
      standard force controller and a 75% reduction in fluctuations when compared to
      manual attempts to maintain the same force.

PMID- 29375281
TI  - Where We Have Been and Where We Are Going: A Content Analysis of Articles
      Published in the Journal of Women's Health Physical Therapy From 2005 to 2015.
AB  - Objective: The objective of this study was to examine the type and content of
      Journal of Women's Health Physical Therapy (JWHPT) publications over the last
      decade. Study Design: Content and bibliometric analysis of published literature.
      Background: Component sections, such as the Section on Women's Health (SoWH) of
      the American Physical Therapy Association provide content expertise to areas of
      specialty physical therapist practice, thereby supporting the dissemination of
      evidence for physical therapists to use. Closely aligned with the mission of the
      SoWH, JWHPT provides evidence reflecting this practice area. The purpose of our
      analysis was to examine publications within JWHPT to determine how closely JWHPT
      is meeting the mission and focus of section members. Methods and Measures: We
      used established bibliographic methodology to code and review manuscripts
      published online between 2005 and 2015 in JWHPT using established domains
      (article type, participant type, research design, study purpose, and area of
      focus). Total publications and proportion of publications based on domain were
      described. Impact by citation and author was examined using bibliometric
      software. Results: Eighteen percent of the items published in JWHPT were original
      research papers submitted for the first time. Of those papers, the primary study
      design was cross-sectional experimental research, most commonly studying
      interventions. The primary practice area reported was management of incontinence.
      Conclusions: We suggest that a continued need to increase efforts for the
      submission and publication of a greater proportion of randomized controlled
      trials and metric articles.

PMID- 29375280
TI  - Brain Tumor Diagnostics and Therapeutics with Superparamagnetic Ferrite
      Nanoparticles.
AB  - Ferrite nanoparticles (F-NPs) can transform both cancer diagnostics and
      therapeutics. Superparamagnetic F-NPs exhibit high magnetic moment and
      susceptibility such that in presence of a static magnetic field transverse
      relaxation rate of water protons for MRI contrast is augmented to locate F-NPs
      (i.e., diagnostics) and exposed to an alternating magnetic field local
      temperature is increased to induce tissue necrosis (i.e., thermotherapy). F-NPs
      are modified by chemical synthesis of mixed spinel ferrites as well as their
      size, shape, and coating. Purposely designed drug-containing nanoparticles (D
      NPs) can slowly deliver drugs (i.e., chemotherapy). Convection-enhanced delivery
      (CED) of D-NPs with MRI guidance improves glioblastoma multiforme (GBM)
      treatment. MRI monitors the location of chemotherapy when D-NPs and F-NPs are
      coadministered with CED. However superparamagnetic field gradients produced by F
      NPs complicate MRI readouts (spatial distortions) and MRS (extensive line
      broadening). Since extracellular pH (pHe) is a cancer hallmark, pHe imaging is
      needed to screen cancer treatments. Biosensor imaging of redundant deviation in
      shifts (BIRDS) extrapolates pHe from paramagnetically shifted signals and the pHe
      accuracy remains unaffected by F-NPs. Hence effect of both chemotherapy and
      thermotherapy can be monitored (by BIRDS), whereas location of F-NPs is revealed
      (by MRI). Smarter tethering of nanoparticles and agents will impact GBM
      theranostics.

PMID- 29375282
TI  - Quality-of-Life Outcomes Following Surface Electromyography Biofeedback as an
      Adjunct to Pelvic Floor Muscle Training for Urinary Incontinence: A Case Report.
AB  - Background: A non-invasive treatment for urinary incontinence (UI) is surface
      electromyography (sEMG) biofeedback with pelvic floor muscle (PFM) training. A
      lack of consensus and evidence exists on the Quality of Life (QoL) outcomes
      following sEMG biofeedback using surface electrodes at the perineum compared to
      the more invasive intravaginal probe. This case report examines QoL using sEMG
      biofeedback at the perineum with PFM training for UI. Study Design: Single
      subject case report. Case Description: The patient was a 61-year-old woman
      diagnosed with UI. Her chief complaints were nocturia, urine leakage with
      urgency, and urine leakage with sneezing and coughing. Physical therapy (PT)
      treatment focused on behavioral modification, PFM strengthening with and without
      sEMG biofeedback, and therapeutic exercises with PFM contractions. Outcomes: At
      four weeks from baseline, the patient's PFM strength increased from 2/5 to 4/5
      based on the Modified Laycock Scale. Her PFM endurance contraction improved from
      two seconds to ten seconds. The International Continence Impact Questionnaire -
      Urinary Incontinence Short Form (ICIQ-UI SF) score decreased from 6 to 0, the
      Incontinence Impact Questionnaire - Short Form (IIQ-7) score decreased from 14.3
      to 0, and the 3 Incontinence Questions (3IQ) responses did not change.
      Discussion: The outcomes from this case report demonstrate a brief course of PT
      treatment consisting of perineal sEMG biofeedback in conjunction with PFM
      training demonstrated clinically meaningful improvements in incontinence-related
      QoL, in addition to improvements in motor function in a woman with mixed UI and
      nocturia.

PMID- 29375283
TI  - A long-term cohort study of surgery for recurrent prolapse comparing mesh
      augmented anterior repairs to anterior colporrhaphy.
AB  - Background: There are safety concerns regarding the use of mesh in vaginal
      surgery with a call for long-term follow-up data. This study was designed to
      evaluate the long-term safety and efficacy of vaginal repairs performed for
      recurrent cystocele using Perigee (non-absorbable trans-obturator) mesh. Methods:
      A retrospective consecutive cohort of 48 women who underwent surgery for
      recurrent prolapse between March 2007 and December 2011 in a single centre was
      reviewed. Satisfaction was assessed using the patient global impression of
      improvement (PGI-I). Symptoms were assessed with the pelvic floor distress
      inventory (PFDI). Women were questioned regarding pain, sexual activity and
      pelvic floor surgery performed since the original procedure and examined for
      erosion. Women were compared to 25 controls from a consecutive cohort of repeat
      anterior colporrhapies. Results: The mean length of follow-up was 6.5 years (78
      months; range 48-106). Significantly more women in the mesh group reported that
      they were "much better" or "very much better" (69 vs 40% p = 0.02). The rate of
      mesh erosion at follow-up was 11.6%. Two women in the mesh group required
      surgical excision of eroded mesh in the operating room (4%). The reoperation rate
      for a combination of de novo stress incontinence, recurrent prolapse and mesh
      exposure was similar in each group (33% mesh vs 32% native tissue). Conclusions:
      A vaginal mesh repair using a non-absorbable trans-obturator mesh has improved
      satisfaction compared to an anterior colporrhaphy.

PMID- 29375284
TI  - Conversion of Continuous-Valued Deep Networks to Efficient Event-Driven Networks
      for Image Classification.
AB  - Spiking neural networks (SNNs) can potentially offer an efficient way of doing
      inference because the neurons in the networks are sparsely activated and
      computations are event-driven. Previous work showed that simple continuous-valued
      deep Convolutional Neural Networks (CNNs) can be converted into accurate spiking
      equivalents. These networks did not include certain common operations such as max
      pooling, softmax, batch-normalization and Inception-modules. This paper presents
      spiking equivalents of these operations therefore allowing conversion of nearly
      arbitrary CNN architectures. We show conversion of popular CNN architectures,
      including VGG-16 and Inception-v3, into SNNs that produce the best results
      reported to date on MNIST, CIFAR-10 and the challenging ImageNet dataset. SNNs
      can trade off classification error rate against the number of available
      operations whereas deep continuous-valued neural networks require a fixed number
      of operations to achieve their classification error rate. From the examples of
      LeNet for MNIST and BinaryNet for CIFAR-10, we show that with an increase in
      error rate of a few percentage points, the SNNs can achieve more than 2x
      reductions in operations compared to the original CNNs. This highlights the
      potential of SNNs in particular when deployed on power-efficient neuromorphic
      spiking neuron chips, for use in embedded applications.

PMID- 29375285
TI  - Small RNA Sequencing of Sporadic Amyotrophic Lateral Sclerosis Cerebrospinal
      Fluid Reveals Differentially Expressed miRNAs Related to Neural and Glial
      Activity.
AB  - Amyotrophic lateral sclerosis (ALS) is a clinical subtype of motor neurone
      disease (MND), a fatal neurodegenerative disease involving the loss of both the
      upper and lower motor neurones from the motor cortex, brainstem, and spinal cord.
      Identifying specific disease biomarkers would help to not only improve diagnostic
      delay but also to classify disease subtypes, monitor response to therapeutic
      drugs and track disease progression. miRNAs are small non-coding RNA responsible
      for regulating gene expression and ultimately protein expression and have been
      used as biomarkers for many cancers and neurodegenerative disorders.
      Investigating the detection of miRNAs in cerebrospinal fluid (CSF), the fluid
      that bathes the central nervous system (CNS) is a prime target for identifying
      potential biomarkers for ALS. This is the first study to investigate the
      expression of miRNAs in the CSF of ALS patients using small RNA sequencing. We
      detected 11 differentially expressed miRNAs in the CSF of sporadic ALS (sALS)
      patients related to neural and glial activity. Additionally, miRNAs involved in
      glucose metabolism and the regulation of oxidative stress were also identified.
      Detecting the presence of potential CSF derived miRNA biomarkers in sALS could
      open up a whole new area of knowledge to help gain a better understanding of
      disease pathophysiology. Additionally, with further investigation, the tracking
      of CSF miRNA over the disease course could be used to follow the disease
      progression and monitor the effect of novel therapeutics that could be
      personalized to an individual disease phenotype.

PMID- 29375287
TI  - How Might the Relation of the Development of Hand Preferences to the Development
      of Cognitive Functions be Examined During Infancy: A Sketch?
AB  - Investigations of the relation of the development of hand preferences to the
      development of other sensorimotor and cognitive abilities are plagued by
      confusing and contradictory results. In part, the confusion derives from the
      failure to create accurate, appropriate, and reliable descriptions of the
      development of hand preferences and the cognitive or sensorimotor ability of
      interest. This paper sketches an ideal longitudinal study (from birth through 5
      years) with a large sample size that should provide reliable evidence for the
      understanding of the relation of hand preferences to cognitive development. Since
      hand preference differences would affect the way infants engage in manual actions
      with objects and these differences would likely affect how they come to
      comprehend object relations, differences in the development of cognition across
      handedness groups would be a good test of certain forms of embodiment theory.

PMID- 29375286
TI  - Does Otovestibular Loss in the Autosomal Dominant Disorder DFNA9 Have an Impact
      of on Cognition? A Systematic Review.
AB  - Background and Purpose: Cognitive impairment has been observed in patients with
      bilateral vestibular loss (BVL) and in patients with sensorineural hearing loss
      (SNHL). DFNA9 is an autosomal dominant disorder that causes a combination of both
      sensory deficits by the 3rd to 5th decade. We therefore hypothesize a combined
      detrimental effect on cognition. The aim of this systematic review was to
      identify studies related to DFNA9 in general and its relationship with cognitive
      impairment more specifically. Materials and Methods: Several databases including
      Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of
      Controlled Trials, ISI Web of Knowledge, and Web of Science were searched to
      accumulate information about DFNA9-mutations, including phenotype, genotype,
      pathophysiology, quality of life (QOL), and imaging in general and cognitive
      function more specifically. A qualitative analysis was performed on the 55
      articles that qualified. Results: The clinical features of DFNA9 are different
      along the 24 COCH mutations, described up to now. Vestibular symptoms generally
      present themselves a few years after SNHL onset in mutations associated with the
      vWFA-domain although they can precede SNHL onset in other mutations associated
      with the LCCL-domain. QoL has not been studied extensively in DFNA9, although
      scarce work is available on the positive impact of cochlear implantation to
      rehabilitate hearing. No studies were found evaluating cognition in DFNA9
      patients. Conclusion: Although cognitive impairment has been demonstrated in
      patients with hearing loss as well as in patients with BVL, no studies have been
      reported on the combination of both sensory deficits, such as in DFNA9. Further
      research is warranted to correlate otovestibular status with cognition.

PMID- 29375288
TI  - PAIR Comparison between Two Within-Group Conditions of Resting-State fMRI
      Improves Classification Accuracy.
AB  - Classification approaches have been increasingly applied to differentiate
      patients and normal controls using resting-state functional magnetic resonance
      imaging data (RS-fMRI). Although most previous classification studies have
      reported promising accuracy within individual datasets, achieving high levels of
      accuracy with multiple datasets remains challenging for two main reasons: high
      dimensionality, and high variability across subjects. We used two independent RS
      fMRI datasets (n = 31, 46, respectively) both with eyes closed (EC) and eyes open
      (EO) conditions. For each dataset, we first reduced the number of features to a
      small number of brain regions with paired t-tests, using the amplitude of low
      frequency fluctuation (ALFF) as a metric. Second, we employed a new method for
      feature extraction, named the PAIR method, examining EC and EO as paired
      conditions rather than independent conditions. Specifically, for each dataset, we
      obtained EC minus EO (EC-EO) maps of ALFF from half of subjects (n = 15 for
      dataset-1, n = 23 for dataset-2) and obtained EO-EC maps from the other half (n =
      16 for dataset-1, n = 23 for dataset-2). A support vector machine (SVM) method
      was used for classification of EC RS-fMRI mapping and EO mapping. The mean
      classification accuracy of the PAIR method was 91.40% for dataset-1, and 92.75%
      for dataset-2 in the conventional frequency band of 0.01-0.08 Hz. For cross
      dataset validation, we applied the classifier from dataset-1 directly to dataset
      2, and vice versa. The mean accuracy of cross-dataset validation was 94.93% for
      dataset-1 to dataset-2 and 90.32% for dataset-2 to dataset-1 in the 0.01-0.08 Hz
      range. For the UNPAIR method, classification accuracy was substantially lower
      (mean 69.89% for dataset-1 and 82.97% for dataset-2), and was much lower for
      cross-dataset validation (64.69% for dataset-1 to dataset-2 and 64.98% for
      dataset-2 to dataset-1) in the 0.01-0.08 Hz range. In conclusion, for within
      group design studies (e.g., paired conditions or follow-up studies), we recommend
      the PAIR method for feature extraction. In addition, dimensionality reduction
      with strong prior knowledge of specific brain regions should also be considered
      for feature selection in neuroimaging studies.

PMID- 29375291
TI  - Targeted Serum Metabolite Profiling Identifies Metabolic Signatures in Patients
      with Alzheimer's Disease, Normal Pressure Hydrocephalus and Brain Tumor.
AB  - Progression to AD is preceded by elevated levels of 2,4-dihydroxybutanoic acid
      (2,4-DHB), implicating hypoxia in early pathogenesis. Since hypoxia may play a
      role in multiple CNS disorders, we investigated serum metabolite profiles across
      three disorders, AD, Normal Pressure Hydrocephalus (NPH) and brain tumors (BT).
      Blood samples were collected from 27 NPH and 20 BT patients. The profiles of 21
      metabolites were examined. Additionally, data from 37 AD patients and 46 controls
      from a previous study were analyzed together with the newly acquired data. No
      differences in 2,4-DHB were found across AD, NPH and BT samples. In the BT group,
      the fatty acids were increased as compared to HC and NPH groups, while the ketone
      body 3-hydroxybutyrate was increased as compared to AD. Glutamic acid was
      increased in AD as compared to the HC group. In the AD group, 3-hydroxybutyrate
      tended to be decreased with respect to all other groups (mean values -30% or
      more), but the differences were not statistically significant. Serine was
      increased in NPH as compared to BT. In conclusion, AD, NPH and BT have different
      metabolic profiles. This preliminary study may help in identifying the blood
      based markers that are specific to these three CNS diseases.

PMID- 29375289
TI  - Neuronal Migration and Lamination in the Vertebrate Retina.
AB  - In the retina, like in most other brain regions, developing neurons are arranged
      into distinct layers giving the mature tissue its stratified appearance. This
      process needs to be highly controlled and orchestrated, as neuronal layering
      defects lead to impaired retinal function. To achieve successful neuronal
      layering and lamination in the retina and beyond, three main developmental steps
      need to be executed: First, the correct type of neuron has to be generated at a
      precise developmental time. Second, as most retinal neurons are born away from
      the position at which they later function, newborn neurons have to move to their
      final layer within the developing tissue, a process also termed neuronal
      lamination. Third, these neurons need to connect to their correct synaptic
      partners. Here, we discuss neuronal migration and lamination in the vertebrate
      retina and summarize our knowledge on these aspects of retinal development. We
      give an overview of how lamination emerges and discuss the different modes of
      neuronal translocation that occur during retinogenesis and what we know about the
      cell biological machineries driving them. In addition, retinal mosaics and their
      importance for correct retinal function are examined. We close by stating the
      open questions and future directions in this exciting field.

PMID- 29375290
TI  - No Effects of Non-invasive Brain Stimulation on Multiple Sessions of Object
      Location-Memory Training in Healthy Older Adults.
AB  - Object-location memory (OLM) is known to decline with normal aging, a process
      accelerated in pathological conditions like mild cognitive impairment (MCI). In
      order to maintain cognitive health and to delay the transition from healthy to
      pathological conditions, novel strategies are being explored. Tentative evidence
      suggests that combining cognitive training and anodal transcranial direct current
      stimulation (atDCS), both reported to induce small and often inconsistent
      behavioral improvements, could generate larger or more consistent improvements or
      both, compared to each intervention alone. Here, we explored the combined
      efficacy of these techniques on OLM. In a subject-blind sham-controlled cross
      over design 32 healthy older adults underwent a 3-day visuospatial training
      paired with either anodal (20 min) or sham (30 s) atDCS (1 mA, temporoparietal).
      Subjects were asked to learn the correct object-location pairings on a street
      map, shown over five learning blocks on each training day. Acquisition
      performance was assessed by accuracy on a given learning block in terms of
      percentage of correct responses. Training success (performance on last training
      day) and delayed memory after 1-month were analyzed by mixed model analysis and
      were controlled for gender, age, education, sequence of stimulation and baseline
      performance. Exploratory analysis of atDCS effects on within-session (online) and
      between-session (offline) memory performance were conducted. Moreover, transfer
      effects on similar trained (visuospatial) and less similar (visuo-constructive,
      verbal) untrained memory tasks were explored, both immediately after training,
      and on follow-up. We found that atDCS paired with OLM-training did not enhance
      success in training or performance in 1-month delayed memory or transfer tasks.
      In sum, this study did not support the notion that the combined atDCS-training
      approach improves immediate or delayed OLM in older adults. However, specifics of
      the experimental design, and a non-optimal timing of atDCS between sessions might
      have masked beneficial effects and should be more systematically addressed in
      future studies.

PMID- 29375292
TI  - Conductive Hydrogel Electrodes for Delivery of Long-Term High Frequency Pulses.
AB  - Nerve block waveforms require the passage of large amounts of electrical energy
      at the neural interface for extended periods of time. It is desirable that such
      waveforms be applied chronically, consistent with the treatment of protracted
      immune conditions, however current metal electrode technologies are limited in
      their capacity to safely deliver ongoing stable blocking waveforms. Conductive
      hydrogel (CH) electrode coatings have been shown to improve the performance of
      conventional bionic devices, which use considerably lower amounts of energy than
      conventional metal electrodes to replace or augment sensory neuron function. In
      this study the application of CH materials was explored, using both a
      commercially available platinum iridium (PtIr) cuff electrode array and a novel
      low-cost stainless steel (SS) electrode array. The CH was able to significantly
      increase the electrochemical performance of both array types. The SS electrode
      coated with the CH was shown to be stable under continuous delivery of 2 mA
      square pulse waveforms at 40,000 Hz for 42 days. CH coatings have been shown as a
      beneficial electrode material compatible with long-term delivery of high current,
      high energy waveforms.

PMID- 29375293
TI  - Rostro-Caudal Organization of Connectivity between Cingulate Motor Areas and
      Lateral Frontal Regions.
AB  - According to contemporary views, the lateral frontal cortex is organized along a
      rostro-caudal functional axis with increasingly complex cognitive/behavioral
      control implemented rostrally, and increasingly detailed motor control
      implemented caudally. Whether the medial frontal cortex follows the same
      organization remains to be elucidated. To address this issue, the functional
      connectivity of the 3 cingulate motor areas (CMAs) in the human brain with the
      lateral frontal cortex was investigated. First, the CMAs and their
      representations of hand, tongue, and eye movements were mapped via task-related
      functional magnetic resonance imaging (fMRI). Second, using resting-state fMRI,
      their functional connectivity with lateral prefrontal and lateral motor cortical
      regions of interest (ROIs) were examined. Importantly, the above analyses were
      conducted at the single-subject level to account for variability in individual
      cingulate morphology. The results demonstrated a rostro-caudal functional
      organization of the CMAs in the human brain that parallels that in the lateral
      frontal cortex: the rostral CMA has stronger functional connectivity with
      prefrontal regions and weaker connectivity with motor regions; conversely, the
      more caudal CMAs have weaker prefrontal and stronger motor connectivity.
      Connectivity patterns of the hand, tongue and eye representations within the CMAs
      are consistent with that of their parent CMAs. The parallel rostral-to-caudal
      functional organization observed in the medial and lateral frontal cortex could
      likely contribute to different hierarchies of cognitive-motor control.

PMID- 29375294
TI  - Benchmarking Brain-Computer Interfaces Outside the Laboratory: The Cybathlon
      2016.
AB  - This paper presents a new approach to benchmarking brain-computer interfaces
      (BCIs) outside the lab. A computer game was created that mimics a real-world
      application of assistive BCIs, with the main outcome metric being the time needed
      to complete the game. This approach was used at the Cybathlon 2016, a competition
      for people with disabilities who use assistive technology to achieve tasks. The
      paper summarizes the technical challenges of BCIs, describes the design of the
      benchmarking game, then describes the rules for acceptable hardware, software and
      inclusion of human pilots in the BCI competition at the Cybathlon. The 11
      participating teams, their approaches, and their results at the Cybathlon are
      presented. Though the benchmarking procedure has some limitations (for instance,
      we were unable to identify any factors that clearly contribute to BCI
      performance), it can be successfully used to analyze BCI performance in
      realistic, less structured conditions. In the future, the parameters of the
      benchmarking game could be modified to better mimic different applications (e.g.,
      the need to use some commands more frequently than others). Furthermore, the
      Cybathlon has the potential to showcase such devices to the general public.

PMID- 29375295
TI  - Frontal Control Process in Intentional Forgetting: Electrophysiological Evidence.
AB  - In this study, we aimed to seek for the neural evidence of the inhibition control
      process in directed forgetting (DF). We adopted a modified item-method DF
      paradigm, in which four kinds of cues were involved. In some trials, the words
      were followed by only a forgetting (F) cue. In the other trials, after a word was
      presented, a maintenance (M) cue was presented, followed by an explicit
      remembering (M-R) cue or an forgetting (M-F) cue. Data from 19 healthy adult
      participants showed that, (1) compared with the remembering cue (i.e., M-R cue),
      forgetting cues (i.e., M-F cue and F cue) evoked enhanced frontal N2 and reduced
      parietal P3 and late positive complex (LPC) components, indicating that the
      forgetting cues might trigger a more intensive cognitive control process and that
      fewer amounts of cognitive resources were recruited for the further rehearsal
      process. (2) Both the M cue and the F cue evoked enhanced N2 and decreased P3 and
      LPC components than the M-R or M-F cue. These results might indicate that
      compared with the M-R and M-F cues, both the M and F cues evoked a more intensive
      cognitive control process and decreased attentional resource allocation process.
      (3) The F cue evoked a decreased P2 component and an enhanced N2 component
      relative to the other cues (i.e., M-R, M-F, M), indicating that the F cue
      received fewer amounts of attentional resources and evoked a more intensive
      cognitive control process. Taken together, forgetting cues were associated with
      enhanced N2 activity relative to the maintenance rehearsal process or the
      remembering process, suggesting an enhanced cognitive control process under DF.
      This cognitive control process might reflect the role of inhibition in DF as
      attempting to suppress the ongoing encoding.

PMID- 29375296
TI  - Pannexin 1 Is Critically Involved in Feedback from Horizontal Cells to Cones.
AB  - Retinal horizontal cells (HCs) feed back negatively to cone photoreceptors and in
      that way generate the center/surround organization of bipolar cell receptive
      fields. The mechanism by which HCs inhibit photoreceptors is a matter of debate.
      General consensus exists that horizontal cell activity leads to the modulation of
      the cone Ca-current. This modulation has two components, one fast and the other
      slow. Several mechanisms for this modulation have been proposed: a fast ephaptic
      mechanism, and a slow pH mediated mechanism. Here we test the hypothesis that the
      slow negative feedback signal from HCs to cones is mediated by Panx1 channels
      expressed at the tips of the dendrites of horizontal cell. We generated zebrafish
      lacking Panx1 and found that the slow component of the feedback signal was
      strongly reduced in the mutants showing that Panx1 channels are a fundamental
      part of the negative feedback pathway from HCs to cones.

PMID- 29375297
TI  - Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea.
AB  - Hearing relies on the transmission of auditory information from sensory hair
      cells (HCs) to the brain through the auditory nerve. This relay of information
      requires HCs to be innervated by spiral ganglion neurons (SGNs) in an exclusive
      manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells.
      In the developing auditory nerve, mistargeted SGN axons are retracted or pruned
      and excessive cells are cleared in a process referred to as nerve refinement.
      Whether auditory glial cells are eliminated during auditory nerve refinement is
      unknown. Using early postnatal mice of either sex, we show that glial cell
      numbers decrease after the first postnatal week, corresponding temporally with
      nerve refinement in the developing auditory nerve. Additionally, expression of
      immune-related genes was upregulated and macrophage numbers increase in a manner
      coinciding with the reduction of glial cell numbers. Transient depletion of
      macrophages during early auditory nerve development, using transgenic
      CD11bDTR/EGFP mice, resulted in the appearance of excessive glial cells.
      Macrophage depletion caused abnormalities in myelin formation and transient edema
      of the stria vascularis. Macrophage-depleted mice also showed auditory function
      impairment that partially recovered in adulthood. These findings demonstrate that
      macrophages contribute to the regulation of glial cell number during postnatal
      development of the cochlea and that glial cells play a critical role in hearing
      onset and auditory nerve maturation.

PMID- 29375299
TI  - Disturbed Processing of Contextual Information in HCN3 Channel Deficient Mice.
AB  - Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) in the
      nervous system are implicated in a variety of neuronal functions including
      learning and memory, regulation of vigilance states and pain. Dysfunctions or
      genetic loss of these channels have been shown to cause human diseases such as
      epilepsy, depression, schizophrenia, and Parkinson's disease. The physiological
      functions of HCN1 and HCN2 channels in the nervous system have been analyzed
      using genetic knockout mouse models. By contrast, there are no such genetic
      studies for HCN3 channels so far. Here, we use a HCN3-deficient (HCN3-/-) mouse
      line, which has been previously generated in our group to examine the expression
      and function of this channel in the CNS. Specifically, we investigate the role of
      HCN3 channels for the regulation of circadian rhythm and for the determination of
      behavior. Contrary to previous suggestions we find that HCN3-/- mice show normal
      visual, photic, and non-photic circadian function. In addition, HCN3-/- mice are
      impaired in processing contextual information, which is characterized by
      attenuated long-term extinction of contextual fear and increased fear to a
      neutral context upon repeated exposure.

PMID- 29375298
TI  - Evidence for a Pan-Neurodegenerative Disease Response in Huntington's and
      Parkinson's Disease Expression Profiles.
AB  - Huntington's and Parkinson's Diseases (HD and PD) are neurodegenerative disorders
      that share some pathological features but are disparate in others. For example,
      while both diseases are marked by aberrant protein aggregation in the brain, the
      specific proteins that aggregate and types of neurons affected differ. A better
      understanding of the molecular similarities and differences between these two
      diseases may lead to a more complete mechanistic picture of both the individual
      diseases and the neurodegenerative process in general. We sought to characterize
      the common transcriptional signature of HD and PD as well as genes uniquely
      implicated in each of these diseases using mRNA-Seq data from post mortem human
      brains in comparison to neuropathologically normal controls. The enriched
      biological pathways implicated by HD differentially expressed genes show
      remarkable consistency with those for PD differentially expressed genes and
      implicate the common biological processes of neuroinflammation, apoptosis,
      transcriptional dysregulation, and neuron-associated functions. Comparison of the
      differentially expressed (DE) genes highlights a set of consistently altered
      genes that span both diseases. In particular, processes involving nuclear factor
      kappa-light-chain-enhancer of activated B cells (NFkB) and transcription factor
      cAMP response element-binding protein (CREB) are the most prominent among the
      genes common to HD and PD. When the combined HD and PD data are compared to
      controls, relatively few additional biological processes emerge as significantly
      enriched, suggesting that most pathways are independently seen within each
      disorder. Despite showing comparable numbers of DE genes, DE genes unique to HD
      are enriched in far more coherent biological processes than the DE genes unique
      to PD, suggesting that PD may represent a more heterogeneous disorder. The
      complexity of the biological processes implicated by this analysis provides
      impetus for the development of better experimental models to validate the
      results.

PMID- 29375300
TI  - The Effect of MCM3AP-AS1/miR-211/KLF5/AGGF1 Axis Regulating Glioblastoma
      Angiogenesis.
AB  - Glioblastoma (GBM) is the most aggressive and malignant primary tumor.
      Angiogenesis plays a critical role in the progression of GBM. Previous studies
      have indicated that long non-coding RNAs (lncRNAs) are abnormally expressed in
      various cancers and participate in the regulation of the malignant behaviors of
      tumors. The present study demonstrated that lncRNA antisense 1 to Micro
      chromosome maintenance protein 3-associated protein (MCM3AP-AS1) was upregulated
      whereas miR-211 was downregulated in glioma-associated endothelial cells (GECs).
      Knockdown of MCM3AP-AS1 suppressed the cell viability, migration, and tube
      formation of GECs and played a role in inhibiting angiogenesis of GBM in vitro.
      Furthermore, knockdown of MCM3AP-AS1 increased the expression of miR-211.
      Luciferase reporter assay implicated that miR-211 targeted KLF5 3'-UTR and
      consequently inhibited KLF5 expression. Besides, in this study we found that
      MCM3AP-AS1 knockdown decreased KLF5 and AGGF1 expression by upregulating miR-211.
      In addition, KLF5 was associated with the promoter region of AGGF1. Knockdown of
      KLF5 decreased AGGF1 expression by transcriptional repression, and also inhibited
      the activation of PI3K/AKT and ERK1/2 signaling pathways. Overall, this study
      reveals that MCM3AP-AS1/miR-211/KLF5/AGGF1 axis plays a prominent role in the
      regulation of GBM angiogenesis and also serves as new therapeutic target for the
      anti-angiogenic therapy of glioma.

PMID- 29375301
TI  - The GlyT1 Inhibitor Bitopertin Ameliorates Allodynia and Hyperalgesia in Animal
      Models of Neuropathic and Inflammatory Pain.
AB  - Background: Chronic pain conditions are difficult to treat and the therapeutic
      outcome is frequently unsatisfactory. Changes in excitation/inhibition balance
      within the dorsal horn contribute to the establishment and persistence of chronic
      pain. Thus, facilitation of inhibitory neurotransmission is a promising approach
      to treat chronic pain pharmacologically. Glycine transporter 1 (GlyT1) plays an
      important role in regulating extracellular glycine concentrations. Aim of the
      present study therefore was to investigate whether the specific GlyT1 inhibitor
      bitopertin (RG1678; RO4917838) might constitute a novel treatment for chronic
      pain by facilitating glycinergic inhibition. Methods: Mechanical allodynia and
      thermal hyperalgesia were induced by chronic constriction injury of the sciatic
      nerve or carrageenan injections into the plantar surface of the hind paw in
      rodents. The effect of acute and long-term bitopertin application on the reaction
      threshold to mechanical and thermal stimuli was determined. General activity was
      determined in open field experiments. The glycine concentration in cerebrospinal
      fluid and blood was measured by HPLC. Results: Systemic application of bitopertin
      in chronic pain conditions lead to a significant increase of the reaction
      thresholds to mechanical and thermal stimuli in a time and dose-dependent manner.
      Long-term application of bitopertin effectuated stable beneficial effects over 4
      weeks. Bitopertin did not alter reaction thresholds to stimuli in control animals
      and had no effect on general locomotor activity and anxiety but lead to an
      increased glycine concentration in cerebrospinal fluid. Conclusion: These
      findings suggest that inhibition of the GlyT1 by bitopertin represents a
      promising new approach for the treatment of chronic pain.

PMID- 29375302
TI  - A Novel RNA Editing Sensor Tool and a Specific Agonist Determine Neuronal Protein
      Expression of RNA-Edited Glycine Receptors and Identify a Genomic APOBEC1
      Dimorphism as a New Genetic Risk Factor of Epilepsy.
AB  - C-to-U RNA editing of glycine receptors (GlyR) can play an important role in
      disease progression of temporal lobe epilepsy (TLE) as it may contribute in a
      neuron type-specific way to neuropsychiatric symptoms of the disease. It is
      therefore necessary to develop tools that allow identification of neuron types
      that express RNA-edited GlyR protein. In this study, we identify NH4 as agonist
      of C-to-U RNA edited GlyRs. Furthermore, we generated a new molecular C-to-U RNA
      editing sensor tool that detects Apobec-1- dependent RNA editing in HEPG2 cells
      and rat primary hippocampal neurons. Using this sensor combined with NH4
      application, we were able to identify C-to-U RNA editing-competent neurons and
      expression of C-to-U RNA-edited GlyR protein in neurons. Bioinformatic analysis
      of 1,000 Genome Project Phase 3 allele frequencies coding for human Apobec-1 80M
      and 80I variants showed differences between populations, and the results revealed
      a preference of the 80I variant to generate RNA-edited GlyR protein. Finally, we
      established a new PCR-based restriction fragment length polymorphism (RFLP)
      approach to profile mRNA expression with regard to the genetic APOBEC1 dimorphism
      of patients with intractable temporal lobe epilepsy (iTLE) and found that the
      patients fall into two groups. Patients with expression of the Apobec-1 80I
      variant mostly suffered from simple or complex partial seizures, whereas patients
      with 80M expression exhibited secondarily generalized seizure activity. Thus, our
      method allows the characterization of Apobec-1 80M and 80l variants in the brain
      and provides a new way to epidemiologically and semiologically classify iTLE
      according to the two different APOBEC1 alleles. Together, these results
      demonstrate Apobec-1-dependent expression of RNA-edited GlyR protein in neurons
      and identify the APOBEC1 80I/M-coding alleles as new genetic risk factors for
      iTLE patients.

PMID- 29375304
TI  - Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in
      Vivo and in Vitro.
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative diseases
      characterized with a gradual loss of midbrain substantia nigra (SN) dopamine (DA)
      neurons. An excessive evidence demonstrated that microglia-mediated inflammation
      might be involved in the pathogenesis of PD. Thus, inhibition of
      neuroinflammation might possess a promising potential for PD treatment. Icariin
      (ICA), a single active component extracted from the Herba Epimedii, presents
      amounts of pharmacological properties, such as anti-inflammation, anti-oxidant,
      and anti-aging. Recent studies show ICA produced neuroprotection against brain
      dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are
      fully illuminated. In the present study, two different neurotoxins of 6
      hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS)-induced rat midbrain DA
      neuronal damage were applied to investigate the neuroprotective effects of ICA.
      In addition, primary rat midbrain neuron-glia co-cultures were performed to
      explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data
      showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage
      and inhibited microglia activation and pro-inflammatory factors production via
      the suppression of nuclear factor-kappaB (NF-kappaB) pathway activation. In
      animal results, ICA significantly reduced microglia activation and significantly
      attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior
      changes. Together, ICA could protect DA neurons against LPS- and 6-OHDA-induced
      neurotoxicity both in vivo and in vitro. These actions might be closely
      associated with the inhibition of microglia-mediated neuroinflammation.

PMID- 29375303
TI  - Fragile X Mental Retardation Protein Regulates Activity-Dependent Membrane
      Trafficking and Trans-Synaptic Signaling Mediating Synaptic Remodeling.
AB  - Fragile X syndrome (FXS) is the leading monogenic cause of autism and
      intellectual disability. The disease arises through loss of fragile X mental
      retardation protein (FMRP), which normally exhibits peak expression levels in
      early-use critical periods, and is required for activity-dependent synaptic
      remodeling during this transient developmental window. FMRP canonically binds
      mRNA to repress protein translation, with targets that regulate cytoskeleton
      dynamics, membrane trafficking, and trans-synaptic signaling. We focus here on
      recent advances emerging in these three areas from the Drosophila disease model.
      In the well-characterized central brain mushroom body (MB) olfactory
      learning/memory circuit, FMRP is required for activity-dependent synaptic
      remodeling of projection neurons innervating the MB calyx, with function tightly
      restricted to an early-use critical period. FMRP loss is phenocopied by
      conditional removal of FMRP only during this critical period, and rescued by FMRP
      conditional expression only during this critical period. Consistent with FXS
      hyperexcitation, FMRP loss defects are phenocopied by heightened sensory
      experience and targeted optogenetic hyperexcitation during this critical period.
      FMRP binds mRNA encoding Drosophila ESCRTIII core component Shrub (human CHMP4
      homolog) to restrict Shrub translation in an activity-dependent mechanism only
      during this same critical period. Shrub mediates endosomal membrane trafficking,
      and perturbing Shrub expression is known to interfere with neuronal process
      pruning. Consistently, FMRP loss and Shrub overexpression targeted to projection
      neurons similarly causes endosomal membrane trafficking defects within synaptic
      boutons, and genetic reduction of Shrub strikingly rescues Drosophila FXS model
      defects. In parallel work on the well-characterized giant fiber (GF) circuit,
      FMRP limits iontophoretic dye loading into central interneurons, demonstrating an
      FMRP role controlling core neuronal properties through the activity-dependent
      repression of translation. In the well-characterized Drosophila neuromuscular
      junction (NMJ) model, developmental synaptogenesis and activity-dependent
      synaptic remodeling both require extracellular matrix metalloproteinase (MMP)
      enzymes interacting with the heparan sulfate proteoglycan (HSPG) glypican dally
      like protein (Dlp) to restrict trans-synaptic Wnt signaling, with FXS
      synaptogenic defects alleviated by both MMP and HSPG reduction. This new
      mechanistic axis spanning from activity to FMRP to HSPG-dependent MMP regulation
      modulates activity-dependent synaptogenesis. We discuss future directions for
      these mechanisms, and intersecting research priorities for FMRP in glial and
      signaling interactions.

PMID- 29375305
TI  - Tonically Active alpha2 Subunit-Containing Glycine Receptors Regulate the
      Excitability of Striatal Medium Spiny Neurons.
AB  - Medium spiny neurons (MSNs) of the dorsal striatum represent the first relay of
      cortico-striato-thalamic loop, responsible for the initiation of voluntary
      movements and motor learning. GABAergic transmission exerts the main inhibitory
      control of MSNs. However, MSNs also express chloride-permeable glycine receptors
      (GlyRs) although their subunit composition and functional significance in the
      striatum is unknown. Here, we studied the function of GlyRs in MSNs of young
      adult mice. We show that MSNs express functional GlyRs, with alpha2 being the
      main agonist binding subunit. These receptors are extrasynaptic and depolarizing
      at resting state. The pharmacological inhibition of GlyRs, as well as
      inactivation of the GlyR alpha2 subunit gene hyperpolarize the membrane potential
      of MSNs and increase their action potential firing offset. Mice lacking GlyR
      alpha2 showed impaired motor memory consolidation without any changes in the
      initial motor performance. Taken together, these results demonstrate that
      tonically active GlyRs regulate the firing properties of MSNs and may thus affect
      the function of basal ganglia.

PMID- 29375306
TI  - SIRT1/PGC-1alpha Signaling Promotes Mitochondrial Functional Recovery and Reduces
      Apoptosis after Intracerebral Hemorrhage in Rats.
AB  - Silent information regulator 1 (SIRT1) exerts neuroprotection in many
      neurodegenerative diseases. However, it is not clear if SIRT1 has protective
      effects after intracerebral hemorrhage (ICH)-induced brain injury in rats. Thus,
      our goal was to examine the influence of SIRT1 on ICH injuries and any underlying
      mechanisms of this influence. Brain injury was induced by autologous arterial
      blood (60 MUL) injection into rat brains, and data show that activation of SIRT1
      with SRT1720 (5 mg/kg) restored nuclear SIRT1, deacetylation of PGC-1alpha, and
      mitochondrial biogenesis and decreased mortality, behavioral deficits, and brain
      water content without significant changes in phosphorylated AMP-activated protein
      kinase (pAMPK) induced by ICH. Activation of SIRT1 with SRT1720 also restored
      mitochondrial electron transport chain proteins and decreased apoptotic proteins
      in ICH; however, these changes were reversed after ICH. In contrast, treatment
      with PGC-1alpha siRNA yielded opposite effects. To explore the protective effects
      of SIRT1 after ICH, siRNAs were used to knockdown SIRT1. Treatment with SIRT1
      siRNA increased mortality, behavioral deficits, brain water content,
      mitochondrial dysfunction, and neurocyte apoptosis after ICH. Thus, activation of
      SIRT1 promotes recovery of mitochondrial protein and function by increasing
      mitochondrial biogenesis and reduces apoptosis after ICH via the PGC-1alpha
      mitochondrial pathway. These data may suggest a new therapeutic approach for ICH
      injuries.

PMID- 29375308
TI  - A Protein Aggregation Inhibitor, Leuco-Methylthioninium
      Bis(Hydromethanesulfonate), Decreases alpha-Synuclein Inclusions in a Transgenic
      Mouse Model of Synucleinopathy.
AB  - alpha-Synuclein (alpha-Syn) aggregation is a pathological feature of
      synucleinopathies, neurodegenerative disorders that include Parkinson's disease
      (PD). We have tested whether N,N,N',N'-tetramethyl-10H-phenothiazine-3,7
      diaminium bis(hydromethanesulfonate) (leuco-methylthioninium
      bis(hydromethanesulfonate); LMTM), a tau aggregation inhibitor, affects alpha-Syn
      aggregation in vitro and in vivo. Both cellular and transgenic models in which
      the expression of full-length human alpha-Syn (h-alpha-Syn) fused with a signal
      sequence peptide to promote alpha-Syn aggregation were used. Aggregated alpha-Syn
      was observed following differentiation of N1E-115 neuroblastoma cells transfected
      with h-alpha-Syn. The appearance of aggregated alpha-Syn was inhibited by LMTM,
      with an EC50 of 1.1 MUM, with minimal effect on h-alpha-Syn mRNA levels being
      observed. Two independent lines of mice (L58 and L62) transgenic for the same
      fusion protein accumulated neuronal h-alpha-Syn that, with aging, developed into
      fibrillary inclusions characterized by both resistance to proteinase K (PK)
      cleavage and their ability to bind thiazin red. There was a significant decrease
      in alpha-Syn-positive neurons in multiple brain regions following oral treatment
      of male and female mice with LMTM administered daily for 6 weeks at 5 and 15 mg
      MT/kg. The early aggregates of alpha-Syn and the late-stage fibrillar inclusions
      were both susceptible to inhibition by LMTM, a treatment that also resulted in
      the rescue of movement and anxiety-related traits in these mice. The results
      suggest that LMTM may provide a potential disease modification therapy in PD and
      other synucleinopathies through the inhibition of alpha-Syn aggregation.

PMID- 29375309
TI  - P2X7 Nucleotide and EGF Receptors Exert Dual Modulation of the Dual-Specificity
      Phosphatase 6 (MKP-3) in Granule Neurons and Astrocytes, Contributing to Negative
      Feedback on ERK Signaling.
AB  - Extracellular signal-regulated kinases 1 and 2 (ERK1/2) play a central role in
      the intracellular signaling of P2X7 nucleotide receptors in neurons and glial
      cells. Fine spatio-temporal tuning of mitogen-activated protein (MAP) kinases is
      essential to regulate their biological activity. MAP kinase phosphatases (MKPs)
      are dual specificity protein phosphatases (DUSPs) that dephosphorylate
      phosphothreonine and phosphotyrosine residues in MAP kinases. This study focuses
      on how DUSP, DUSP6/MKP3, a phosphatase specific for ERK1/2 is regulated by the
      P2X7 nucleotide receptor in cerebellar granule neurons and astrocytes.
      Stimulation with the specific P2X7 agonist, BzATP, or epidermal growth factor
      (EGF) (positive control for ERK activation) regulates the levels of DUSP6 in a
      time dependent manner. Both agonists promote a decline in DUSP6 protein, reaching
      minimal levels after 30 min yet recovering to basal levels after 1 h. The initial
      loss of protein occurs through proteasomal degradation, as confirmed in
      experiments with the proteasome inhibitor, MG-132. Studies carried out with
      Actinomycin D demonstrated that the enhanced transcription of the Dusp6 gene is
      responsible for recovering the DUSP6 protein levels. Interestingly, ERK1/2
      proteins are involved in the biphasic regulation of the protein phosphatase,
      being required for both the degradation and the recovery phase. We show that
      direct Ser197 phosphorylation of DUSP6 by ERK1/2 proteins could be part of the
      mechanism regulating their cytosolic levels, at least in glial cells. Thus, the
      ERK1/2 activated by P2X7 receptors exerts positive feedback on these kinase's own
      activity, promoting the degradation of one of their major inactivators in the
      cytosolic compartment, DUSP6, both in granule neurons and astrocytes. This
      feedback loop seems to function as a common universal mechanism to regulate ERK
      signaling in neural and non-neural cells.

PMID- 29375307
TI  - AMPA Receptor Trafficking in Natural and Pathological Aging.
AB  - alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs)
      enable most excitatory transmission in the brain and are crucial for mediating
      basal synaptic strength and plasticity. Because of the importance of their
      function, AMPAR dynamics, activity and subunit composition undergo a tight
      regulation which begins as early as prenatal development and continues through
      adulthood. Accumulating evidence suggests that the precise regulatory mechanisms
      involved in orchestrating AMPAR trafficking are challenged in the aging brain. In
      turn dysregulation of AMPARs can be linked to most neurological and
      neurodegenerative disorders. Understanding the mechanisms that govern AMPAR
      signaling during natural and pathological cognitive decline will guide the
      efforts to develop most effective ways to tackle neurodegenerative diseases which
      are one of the primary burdens afflicting an increasingly aging population. In
      this review, I provide a brief overview of the molecular mechanisms involved in
      AMPAR trafficking highlighting what is currently known about how these processes
      change with age and disease. As a particularly well-studied example of AMPAR
      dysfunction in pathological aging I focus in Alzheimer's disease (AD) with
      special emphasis in how the production of neurofibrillary tangles (NFTs) and
      amyloid-beta plaques may contribute to disruption in AMPAR function.

PMID- 29375310
TI  - Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of
      Fragile X Syndrome.
AB  - Fragile X syndrome (FXS), the most common form of inherited intellectual
      disability, is also highly associated with autism spectrum disorders (ASD). It is
      caused by expansion of a CGG repeat sequence on the X chromosome resulting in
      silencing of the FMR1 gene. This is modeled in the mouse by deletion of Fmr1
      (Fmr1 KO). Fmr1 KO mice recapitulate many of the behavioral features of the
      disorder including seizure susceptibility, hyperactivity, impaired social
      behavior, sleep problems, and learning and memory deficits. The mammalian target
      of rapamycin pathway (mTORC1) is upregulated in Fmr1 KO mice and is thought to be
      important for the pathogenesis of this disorder. We treated Fmr1 KO mice
      chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin
      treatment could reverse behavioral phenotypes. We performed open field, zero
      maze, social behavior, sleep, passive avoidance, and audiogenic seizure testing.
      We found that pS6 was upregulated in Fmr1 KO mice and normalized by rapamycin
      treatment, but, except for an anxiogenic effect, it did not reverse any of the
      behavioral phenotypes examined. In fact, rapamycin treatment had an adverse
      effect on sleep and social behavior in both control and Fmr1 KO mice. These
      results suggest that targeting the mTOR pathway in FXS is not a good treatment
      strategy and that other pathways should be considered.

PMID- 29375311
TI  - Profiling and Co-expression Network Analysis of Learned Helplessness Regulated
      mRNAs and lncRNAs in the Mouse Hippocampus.
AB  - Although studies provide insights into the neurobiology of stress and depression,
      the exact molecular mechanisms underlying their pathologies remain largely
      unknown. Long non-coding RNA (lncRNA) has been implicated in brain functions and
      behavior. A potential link between lncRNA and psychiatric disorders has been
      proposed. However, it remains undetermined whether IncRNA regulation, in the
      brain, contributes to stress or depression pathologies. In this study, we used a
      valid animal model of depression-like symptoms; namely learned helplessness, RNA
      seq, Gene Ontology and co-expression network analyses to profile the expression
      pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346
      differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein
      coding mRNAs were differentially expressed in helpless mice in comparison with
      control and/or non-helpless mice (inescapable stress resilient mice). Gene
      Ontology and pathway enrichment analyses indicated that induction of helplessness
      altered expression of mRNAs enriched in fundamental biological functions
      implicated in stress/depression neurobiology such as synaptic, metabolic, cell
      survival and proliferation, developmental and chromatin modification functions.
      To explore the possible regulatory roles of the altered lncRNAs, we constructed
      co-expression networks composed of the lncRNAs and mRNAs. Among our
      differentially expressed lncRNAs, 17% showed significant correlation with genes.
      Functional co-expression analysis linked the identified lncRNAs to several
      cellular mechanisms implicated in stress/depression neurobiology. Importantly,
      57% of the identified regulatory lncRNAs significantly correlated with 18
      different synapse-related functions. Thus, the current study identifies for the
      first time distinct groups of lncRNAs regulated by induction of learned
      helplessness in the mouse brain. Our results suggest that lncRNA-directed
      regulatory mechanisms might contribute to stress-induced pathologies; in
      particular, to inescapable stress-induced synaptic modifications.

PMID- 29375312
TI  - The Beta Adrenergic Receptor Blocker Propranolol Counteracts Retinal Dysfunction
      in a Mouse Model of Oxygen Induced Retinopathy: Restoring the Balance between
      Apoptosis and Autophagy.
AB  - In a mouse model of oxygen induced retinopathy (OIR), beta adrenergic receptor
      (BAR) blockade has been shown to recover hypoxia-associated retinal damages.
      Although the adrenergic signaling is an important regulator of apoptotic and
      autophagic processes, the role of BARs in retinal cell death remains to be
      elucidated. The present study was aimed at investigating whether ameliorative
      effects of BAR blockers may occur through their coordinated action on apoptosis
      and autophagy. To this aim, retinas from control and OIR mice untreated or
      treated with propranolol, a non-selective BAR1/2 blocker, were characterized in
      terms of expression and localization of apoptosis and autophagy markers. The
      effects of propranolol on autophagy signaling were also evaluated and specific
      autophagy modulators were used to get functional information on the autophagic
      effects of BAR antagonism. Finally, propranolol effects on neurodegenerative
      processes were associated to an electrophysiological investigation of retinal
      function by recording electroretinogram (ERG). We found that retinas of OIR mice
      are characterized by increased apoptosis and decreased autophagy, while
      propranolol reduces apoptosis and stimulates autophagy. In particular,
      propranolol triggers autophagosome formation in bipolar, amacrine and ganglion
      cells that are committed to die by apoptosis in response to hypoxia. Also our
      data argue that propranolol, through the inhibition of the Akt-mammalian target
      of rapamycin pathway, activates autophagy which decreases retinal cell death. At
      the functional level, propranolol recovers dysfunctional ERG by recovering the
      amplitude of a- and b-waves, and oscillatory potentials, thus indicating an
      efficient restoring of retinal transduction. Overall, our results demonstrate
      that BAR1/2 are key regulators of retinal apoptosis/autophagy, and that BAR1/2
      blockade leads to autophagy-mediated neuroprotection. Reinstating the balance
      between apoptotic and autophagic machines may therefore be viewed as a future
      goal in the treatment of retinopathies.

PMID- 29375313
TI  - Proteomic and Metabolomic Analyses of Vanishing White Matter Mouse Astrocytes
      Reveal Deregulation of ER Functions.
AB  - Vanishing white matter (VWM) is a leukodystrophy with predominantly early
      childhood onset. Affected children display various neurological signs, including
      ataxia and spasticity, and die early. VWM patients have bi-allelic mutations in
      any of the five genes encoding the subunits of the eukaryotic translation factor
      2B (eIF2B). eIF2B regulates protein synthesis rates under basal and cellular
      stress conditions. The underlying molecular mechanism of how mutations in eIF2B
      result in VWM is unknown. Previous studies suggest that brain white matter
      astrocytes are primarily affected in VWM. We hypothesized that the translation
      rate of certain astrocytic mRNAs is affected by the mutations, resulting in
      astrocytic dysfunction. Here we subjected primary astrocyte cultures of wild type
      (wt) and VWM (2b5ho ) mice to pulsed labeling proteomics based on stable isotope
      labeling with amino acids in cell culture (SILAC) with an L-azidohomoalanine
      (AHA) pulse to select newly synthesized proteins. AHA was incorporated into newly
      synthesized proteins in wt and 2b5ho astrocytes with similar efficiency, without
      affecting cell viability. We quantified proteins synthesized in astrocytes of wt
      and 2b5ho mice. This proteomic profiling identified a total of 80 proteins that
      were regulated by the eIF2B mutation. We confirmed increased expression of PROS1
      in 2b5ho astrocytes and brain. A DAVID enrichment analysis showed that
      approximately 50% of the eIF2B-regulated proteins used the secretory pathway. A
      small-scale metabolic screen further highlighted a significant change in the
      metabolite 6-phospho-gluconate, indicative of an altered flux through the pentose
      phosphate pathway (PPP). Some of the proteins migrating through the secretory
      pathway undergo oxidative folding reactions in the endoplasmic reticulum (ER),
      which produces reactive oxygen species (ROS). The PPP produces NADPH to remove
      ROS. The proteomic and metabolomics data together suggest a deregulation of ER
      function in 2b5ho mouse astrocytes.

PMID- 29375315
TI  - The Calcineurin Inhibitor FK506 Prevents Cognitive Impairment by Inhibiting
      Reactive Astrogliosis in Pilocarpine-Induced Status Epilepticus Rats.
AB  - Status epilepticus (SE) is a severe clinical manifestation of epilepsy
      accompanying with cognitive impairment and brain damage. Astrocyte activation
      occurs following seizures and plays an important role in epilepsy-induced
      pathological injury, including cognitive impairment. FK506, an immunosuppressant
      used in clinical settings to prevent allograft rejection, has been shown to
      exhibit neuroprotective effects in central nervous system diseases. The present
      study was designed to investigate the effect of FK506 on cognitive impairment in
      a lithium-pilocarpine-induced SE rat model. It's found that FK506 treatment
      significantly increased the latency period to seizures and decreased the maximal
      intensity of seizures. FK506 treatment also markedly increased the surviving
      cells and reduced the neuron apoptosis after seizures. Meanwhile, FK506 treatment
      reduced the escape latency and prolonged the swimming distance in the Morris
      water maze test. In addition, FK506 treatment down-regulated the expression level
      of GFAP, a specific marker of astrocytes. In conclusion, FK506 could prevent and
      recover cognitive impairment by inhibiting reactive astrogliosis in pilocarpine
      induced status epilepticus rats, suggesting that FK506 may be a promising agent
      for the treatment of epilepsy.

PMID- 29375314
TI  - Intrinsic and Extrinsic Neuromodulation of Olfactory Processing.
AB  - Neuromodulation is a ubiquitous feature of neural systems, allowing flexible,
      context specific control over network dynamics. Neuromodulation was first
      described in invertebrate motor systems and early work established a basic
      dichotomy for neuromodulation as having either an intrinsic origin (i.e., neurons
      that participate in network coding) or an extrinsic origin (i.e., neurons from
      independent networks). In this conceptual dichotomy, intrinsic sources of
      neuromodulation provide a "memory" by adjusting network dynamics based upon
      previous and ongoing activation of the network itself, while extrinsic
      neuromodulators provide the context of ongoing activity of other neural networks.
      Although this dichotomy has been thoroughly considered in motor systems, it has
      received far less attention in sensory systems. In this review, we discuss
      intrinsic and extrinsic modulation in the context of olfactory processing in
      invertebrate and vertebrate model systems. We begin by discussing presynaptic
      modulation of olfactory sensory neurons by local interneurons (LNs) as a
      mechanism for gain control based on ongoing network activation. We then discuss
      the cell-class specific effects of serotonergic centrifugal neurons on olfactory
      processing. Finally, we briefly discuss the integration of intrinsic and
      extrinsic neuromodulation (metamodulation) as an effective mechanism for exerting
      global control over olfactory network dynamics. The heterogeneous nature of
      neuromodulation is a recurring theme throughout this review as the effects of
      both intrinsic and extrinsic modulation are generally non-uniform.

PMID- 29375317
TI  - Neuregulin 1 Reduces Motoneuron Cell Death and Promotes Neurite Growth in an in
      Vitro Model of Motoneuron Degeneration.
AB  - Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder
      with no effective treatment currently available. Although the mechanisms of
      motoneuron (MN) death are still unclear, glutamate excitotoxicity and
      neuroinflammatory reaction are two main features in the neurodegenerative process
      of ALS. Neuregulin 1 (NRG1) is a trophic factor highly expressed in MNs and
      neuromuscular junctions. Several recent evidences suggest that NRG1 and their
      ErbB receptors are involved in ALS. However, further knowledge is still needed to
      clarify the role of the NRG1-ErbB pathway on MN survival. In this study we used
      an in vitro model of spinal cord organotypic cultures (SCOCs) subject to chronic
      excitotoxicity caused by DL-threo-beta-hydroxyaspartic acid (THA) to characterize
      the effect of NRG1 on MN survival. Our results show that addition of recombinant
      human NRG1 (rhNRG1) to the medium significantly increased MN survival through the
      activation of ErbB receptors which was ablated with lapatinib (LP), an ErbB
      inhibitor, and reduced microglial reactivity overcoming the excitotoxicity
      effects. rhNRG1 activated the pro-survival PI3K/AKT pathway and restored the
      autophagic flux in the spinal cord culture. Moreover, addition of rhNRG1 to the
      medium promoted motor and sensory neurite outgrowth. These findings indicate that
      increasing NRG1 at the spinal cord is an interesting approach for promoting MN
      protection and regeneration.

PMID- 29375318
TI  - Neuroprotection Exerted by Netrin-1 and Kinesin Motor KIF1A in Secondary Brain
      Injury following Experimental Intracerebral Hemorrhage in Rats.
AB  - Binding of extracellular netrin-1 to its receptors, deleted in colorectal cancer
      (DCC) and uncoordinated gene 5H2 (UNC5H2), inhibits apoptosis mediated by these
      receptors. A neuron-specific kinesin motor protein, KIF1A, has been shown to
      participate in netrin-1 secretion. This study aimed to identify the roles of
      netrin-1 and KIF1A in secondary brain injury after intracerebral hemorrhage (ICH)
      and the potential mechanisms. An autologous blood ICH model was established in
      adult male Sprague-Dawley rats, and cultured neurons were exposed to OxyHb to
      mimic ICH conditions in vitro. Mouse recombinant netrin-1, expression vectors
      encoding KIF1A, and KIF1A-specific siRNAs were administered
      intracerebroventricularly. After ICH, protein levels of netrin-1, DCC, and UNC5H2
      increased, while protein levels of KIF1A decreased. Levels of UNC5H2 and DCC
      bound to netrin-1 increased after ICH but were significantly lower than the
      increase in total amount of protein. Administration of recombinant netrin-1
      attenuated neuronal apoptosis and degeneration in ICH rats. Moreover, KIF1A
      overexpression increased concentrations of netrin-1 in cerebrospinal fluid and
      cell culture supernatant and exerted neuroprotective effects via netrin-1 and its
      receptor pathways. KIF1A plays a critical role in netrin-1 secretion by neurons.
      An increase in protein levels of netrin-1 may be a neuroprotective strategy after
      ICH. However, this process is almost completely abolished by ICH-induced loss of
      KIF1A. An exogenous increase of KIF1A may be a potential strategy for
      neuroprotection via the netrin-1 pathway.

PMID- 29375316
TI  - Biomaterial-Supported Cell Transplantation Treatments for Spinal Cord Injury:
      Challenges and Perspectives.
AB  - Spinal cord injury (SCI), resulting in para- and tetraplegia caused by the
      partial or complete disruption of descending motor and ascending sensory neurons,
      represents a complex neurological condition that remains incurable. Following
      SCI, numerous obstacles comprising of the loss of neural tissue (neurons,
      astrocytes, and oligodendrocytes), formation of a cavity, inflammation, loss of
      neuronal circuitry and function must be overcome. Given the multifaceted primary
      and secondary injury events that occur with SCI treatment options are likely to
      require combinatorial therapies. While several methods have been explored, only
      the intersection of two, cell transplantation and biomaterial implantation, will
      be addressed in detail here. Owing to the constant advance of cell culture
      technologies, cell-based transplantation has come to the forefront of SCI
      treatment in order to replace/protect damaged tissue and provide physical as well
      as trophic support for axonal regrowth. Biomaterial scaffolds provide cells with
      a protected environment from the surrounding lesion, in addition to bridging
      extensive damage and providing physical and directional support for axonal
      regrowth. Moreover, in this combinatorial approach cell transplantation improves
      scaffold integration and therefore regenerative growth potential. Here, we review
      the advances in combinatorial therapies of Schwann cells (SCs), astrocytes,
      olfactory ensheathing cells (OECs), mesenchymal stem cells, as well as neural
      stem and progenitor cells (NSPCs) with various biomaterial scaffolds.

PMID- 29375319
TI  - Preserved Function of Afferent Parvalbumin-Positive Perisomatic Inhibitory
      Synapses of Dentate Granule Cells in Rapidly Kindled Mice.
AB  - Parvalbumin- (PV-) containing basket cells constitute perisomatic GABAergic
      inhibitory interneurons innervating principal cells at perisomatic area, a
      strategic location that allows them to efficiently control the output and
      synchronize oscillatory activity at gamma frequency (30-90 Hz) oscillations. This
      oscillatory activity can convert into higher frequency epileptiform activity, and
      therefore could play an important role in the generation of seizures. However,
      the role of endogenous modulators of seizure activity, such as Neuropeptide Y
      (NPY), has not been fully explored in at PV input and output synapses. Here,
      using selective optogenetic activation of PV cells in the hippocampus, we show
      that seizures, induced by rapid kindling (RK) stimulations, enhance gamma
      aminobutyric acid (GABA) release from PV cells onto dentate gyrus (DG) granule
      cells (GC). However, PV-GC synapses did not differ between controls and kindled
      animals in terms of GABA release probability, short-term plasticity and
      sensitivity to NPY. Kinetics of gamma-aminobutyric acid A (GABA-A) mediated
      currents in postsynaptic GC were also unaffected. When challenged by repetitive
      high-frequency optogenetic stimulations, PV synapses in kindled animals responded
      with enhanced GABA release onto GC. These results unveil a mechanism that might
      possibly contribute to the generation of abnormal synchrony and maintenance of
      epileptic seizures.

PMID- 29375320
TI  - Systematic Analysis of mRNA and miRNA Expression of 3D-Cultured Neural Stem Cells
      (NSCs) in Spaceflight.
AB  - Recently, with the development of the space program there are growing concerns
      about the influence of spaceflight on tissue engineering. The purpose of this
      study was thus to determine the variations of neural stem cells (NSCs) during
      spaceflight. RNA-Sequencing (RNA-Seq) based transcriptomic profiling of NSCs
      identified many differentially expressed mRNAs and miRNAs between space and earth
      groups. Subsequently, those genes with differential expression were subjected to
      bioinformatic evaluation using gene ontology (GO), Kyoto Encyclopedia of Genes
      and Genomes pathway (KEGG) and miRNA-mRNA network analyses. The results showed
      that NSCs maintain greater stemness ability during spaceflight although the
      growth rate of NSCs was slowed down. Furthermore, the results indicated that NSCs
      tended to differentiate into neuron in outer space conditions. Detailed genomic
      analyses of NSCs during spaceflight will help us to elucidate the molecular
      mechanisms behind their differentiation and proliferation when they are in outer
      space.

PMID- 29375322
TI  - Intense Activity of the Raphe Spinal Pathway Depresses Motor Activity via a
      Serotonin Dependent Mechanism.
AB  - Motor fatigue occurring during prolonged physical activity has both peripheral
      and central origins. It was previously demonstrated that the excitability of
      motoneurons was decreased when a spillover of serotonin could activate
      extrasynaptic 5-HT1A receptors at the axon initial segment (AIS) of motoneurons.
      Here we investigated the impact of massive synaptic release of serotonin on motor
      behavior in an integrated preparation of the adult turtle performing fictive
      scratching behaviors. We found that a prolonged electrical stimulation of the
      raphe spinal pathway induced a reversible inhibition of the motor behavior that
      lasted several tens of seconds. The effect disappeared when the spinal cord was
      perfused with an antagonist for 5-HT1A receptors. By demonstrating a direct
      impact of serotonin on motor behavior, we suggest a central role of this
      monoamine behind central fatigue.

PMID- 29375321
TI  - Temporal Progression of Retinal Progenitor Cell Identity: Implications in Cell
      Replacement Therapies.
AB  - Retinal degenerative diseases, which lead to the death of rod and cone
      photoreceptor cells, are the leading cause of inherited vision loss worldwide.
      Induced pluripotent or embryonic stem cells (iPSCs/ESCs) have been proposed as a
      possible source of new photoreceptors to restore vision in these conditions. The
      proof of concept studies carried out in mouse models of retinal degeneration over
      the past decade have highlighted several limitations for cell replacement in the
      retina, such as the low efficiency of cone photoreceptor production from stem
      cell cultures and the poor integration of grafted cells in the host retina.
      Current protocols to generate photoreceptors from stem cells are largely based on
      the use of extracellular factors. Although these factors are essential to induce
      the retinal progenitor cell (RPC) fate from iPSCs/ESCs, developmental studies
      have shown that RPCs alter fate output as a function of time (i.e., their
      temporal identity) to generate the seven major classes of retinal cell types,
      rather than spatial position. Surprisingly, current stem cell differentiation
      protocols largely ignore the intrinsic temporal identity of dividing RPCs, which
      we argue likely explains the low efficiency of cone production in such cultures.
      In this article, we briefly review the mechanisms regulating temporal identity in
      RPCs and discuss how they could be exploited to improve cone photoreceptor
      production for cell replacement therapies.

PMID- 29375323
TI  - Fear Learning Regulates Cortical Sensory Representations by Suppressing
      Habituation.
AB  - Projections from auditory cortex to the amygdala are thought to contribute to the
      induction of auditory fear learning. In addition, fear conditioning has been
      found to enhance cortical responses to conditioned tones, suggesting that
      cortical plasticity contributes to fear learning. However, the functional role of
      auditory cortex in the retrieval of fear memories is unclear and how fear
      learning regulates cortical sensory representations is not well understood. To
      address these questions, we use acute optogenetic silencing and chronic two
      photon calcium imaging in mouse auditory cortex during fear learning.
      Longitudinal imaging of neuronal ensemble activity reveals that discriminative
      fear learning modulates cortical sensory representations via the suppression of
      cortical habituation.

PMID- 29375324
TI  - Neuronal Assemblies Evidence Distributed Interactions within a Tactile
      Discrimination Task in Rats.
AB  - Accumulating evidence suggests that neural interactions are distributed and
      relate to animal behavior, but many open questions remain. The neural assembly
      hypothesis, formulated by Hebb, states that synchronously active single neurons
      may transiently organize into functional neural circuits-neuronal assemblies
      (NAs)-and that would constitute the fundamental unit of information processing in
      the brain. However, the formation, vanishing, and temporal evolution of NAs are
      not fully understood. In particular, characterizing NAs in multiple brain regions
      over the course of behavioral tasks is relevant to assess the highly distributed
      nature of brain processing. In the context of NA characterization, active tactile
      discrimination tasks with rats are elucidative because they engage several
      cortical areas in the processing of information that are otherwise masked in
      passive or anesthetized scenarios. In this work, we investigate the dynamic
      formation of NAs within and among four different cortical regions in long-range
      fronto-parieto-occipital networks (primary somatosensory, primary visual,
      prefrontal, and posterior parietal cortices), simultaneously recorded from seven
      rats engaged in an active tactile discrimination task. Our results first confirm
      that task-related neuronal firing rate dynamics in all four regions is
      significantly modulated. Notably, a support vector machine decoder reveals that
      neural populations contain more information about the tactile stimulus than the
      majority of single neurons alone. Then, over the course of the task, we identify
      the emergence and vanishing of NAs whose participating neurons are shown to
      contain more information about animal behavior than randomly chosen neurons.
      Taken together, our results further support the role of multiple and distributed
      neurons as the functional unit of information processing in the brain (NA
      hypothesis) and their link to active animal behavior.

PMID- 29375325
TI  - Development of Circumventricular Organs in the Mirror of Zebrafish Enhancer-Trap
      Transgenics.
AB  - The circumventricular organs (CVOs) are small structures lining the cavities of
      brain ventricular system. They are associated with the semitransparent regions of
      the blood-brain barrier (BBB). Hence it is thought that CVOs mediate biochemical
      signaling and cell exchange between the brain and systemic blood. Their
      classification is still controversial and development not fully understood
      largely due to an absence of tissue-specific molecular markers. In a search for
      molecular determinants of CVOs we studied the green fluorescent protein (GFP)
      expression pattern in several zebrafish enhancer trap transgenics including
      Gateways (ET33-E20) that has been instrumental in defining the development of
      choroid plexus. In Gateways the GFP is expressed in regions of the developing
      brain outside the choroid plexus, which remain to be characterized. The
      neuroanatomical and histological analysis suggested that some previously
      unassigned domains of GFP expression may correspond to at least six other CVOs
      the organum vasculosum laminae terminalis (OVLT), subfornical organ (SFO),
      paraventricular organ (PVO), pineal (epiphysis), area postrema (AP) and median
      eminence (ME). Two other CVOs, parapineal and subcommissural organ (SCO) were
      detected in other enhancer-trap transgenics. Hence enhancer-trap transgenic lines
      could be instrumental for developmental studies of CVOs in zebrafish and
      understanding of the molecular mechanism of disease such a hydrocephalus in
      human. Their future analysis may shed light on general and specific molecular
      mechanisms that regulate development of CVOs.

PMID- 29375331
TI  - Bidirectional Control of Reversal in a Dual Action Task by Direct and Indirect
      Pathway Activation in the Dorsolateral Striatum in Mice.
AB  - The striatum is a key brain structure involved in the processing of cognitive
      flexibility, which results from the balance between the flexibility demanded for
      novel learning of motor actions and the inflexibility required to preserve
      previously learned actions. In particular, the dorsolateral portion of the
      striatum (DLS) is engaged in the learning of action sequence. This process is
      temporally driven by fine adjustments in the function of the two main neuronal
      populations of the striatum, known as the direct pathway medium spiny neurons
      (dMSNs) and indirect pathway medium spiny neurons (iMSNs). Here, using
      optogenetics, behavioral, and electrophysiological tools, we addressed the
      relative role of both neuronal populations in the acquisition of a reversal dual
      action sequence in the DLS. While the channelrhodopsin-induced activation of
      dMSNs and iMSNs of the DLS did not induce changes in the learning rate of the
      sequence, the specific activation of the dMSNs of the DLS facilitated the
      acquisition of a reversal dual action sequence; the activation of iMSNs induced a
      significant deficit in the acquisition of the same task. Taken together our
      results indicate an antagonistic relationship between dMSNs and iMSNs on the
      acquisition of a reversal dual action sequence.

PMID- 29375326
TI  - Stereological Assessments of Neuronal Pathology in Auditory Cortex in
      Schizophrenia.
AB  - It has long been known that auditory processing is disrupted in schizophrenia.
      More recently, postmortem studies have provided direct evidence that
      morphological alterations to neurons in auditory cortex are implicated in the
      pathophysiology of this illness, confirming previous predictions. Potential
      neural substrates for auditory impairment and gray matter loss in auditory cortex
      in schizophrenia have been identified, described, and are the focus of this
      review article. Pyramidal cell somal volume is reduced in auditory cortex, as are
      dendritic spine density and number in schizophrenia. Pyramidal cells are not lost
      in this region in schizophrenia, indicating that dendritic spine reductions
      reflect fewer spines per pyramidal cell, consistent with the reduced neuropil
      hypothesis of schizophrenia. Stereological methods have aided in the proper
      collection, reporting and interpretation of this data. Mechanistic studies
      exploring relationships between genetic risk for schizophrenia and altered
      dendrite morphology represent an important avenue for future research in order to
      further elucidate cellular pathology in auditory cortex in schizophrenia.

PMID- 29375328
TI  - Glial- and Neuronal-Specific Expression of CCL5 mRNA in the Rat Brain.
AB  - Chemokine (C-C motif) ligand 5 (CCL5) belongs to a group of chemokines that play
      a role in the peripheral immune system, mostly as chemoattractant molecules, and
      mediate tactile allodynia. In the central nervous system (CNS), CCL5 and its
      receptors have multiple functions, including promoting neuroinflammation, insulin
      signaling, neuromodulator of synaptic activity and neuroprotection against a
      variety of neurotoxins. Evidence has also suggested that this chemokine may
      regulate opioid response. The multifunctional profile of CCL5 might correlate
      with its ability to bind different chemokine receptors, as well as with its
      unique cellular expression. In this work, we have used fluorescence in situ
      hybridization combined with immunohistochemistry to examine the expression
      profile of CCL5 mRNA in the adult rat brain and provide evidence of its cellular
      localization. We have observed that the highest expression of CCL5 mRNA occurs in
      all major fiber tracts, including the corpus callosum, anterior commissure, and
      cerebral peduncle. In these tracts, CCL5 mRNA was localized in oligodendrocytes,
      astrocytes and microglia. Astrocytic and microglial expression was also evident
      in several brain areas including the cerebral cortex, caudate/putamen,
      hippocampus, and thalamus. Furthermore, using a specific neuronal marker, we
      observed CCL5 mRNA expression in discrete layers of the cortex and hippocampus.
      Interestingly, in the midbrain, CCL5 mRNA co-localized with tyrosine hydroxylase
      (TH) positive cells of the ventral tegmental area, suggesting that CCL5 might be
      expressed by a subset of dopaminergic neurons of the mesolimbic system. The
      expression of CCL5 mRNA and protein, together with its receptors, in selected
      brain cell populations proposes that this chemokine could be involved in
      neuronal/glial communication.

PMID- 29375330
TI  - Evidence of Rapid Modulation by Social Information of Subjective, Physiological,
      and Neural Responses to Emotional Expressions.
AB  - Recent research suggests that conceptual or emotional factors could influence the
      perceptual processing of stimuli. In this article, we aimed to evaluate the
      effect of social information (positive, negative, or no information related to
      the character of the target) on subjective (perceived and felt valence and
      arousal), physiological (facial mimicry) as well as on neural (P100 and N170)
      responses to dynamic emotional facial expressions (EFE) that varied from neutral
      to one of the six basic emotions. Across three studies, the results showed
      reduced ratings of valence and arousal of EFE associated with incongruent social
      information (Study 1), increased electromyographical responses (Study 2), and
      significant modulation of P100 and N170 components (Study 3) when EFE were
      associated with social (positive and negative) information (vs. no information).
      These studies revealed that positive or negative social information reduces
      subjective responses to incongruent EFE and produces a similar neural and
      physiological boost of the early perceptual processing of EFE irrespective of
      their congruency. In conclusion, the article suggests that the presence of
      positive or negative social context modulates early physiological and neural
      activity preceding subsequent behavior.

PMID- 29375327
TI  - Ultrastructural Features of Neurovascular Units in a Rat Model of Chronic
      Compressive Spinal Cord Injury.
AB  - Chronic spinal cord compression is the most common cause of spinal cord
      impairment worldwide. Objective of this study is to assess the ultrastructural
      features of the neurovascular unit (NVU) in a rat model of chronic compressive
      spinal cord injury, 24 SD rats were divided into two groups: the control group (n
      = 12), and the compression group (n = 12). A C6 semi-laminectomy was performed in
      the control group, whereas a water-absorbent polyurethane polymer was implanted
      into the C6 epidural space in the compression group. The Basso Beattie Bresnahan
      (BBB) scores and the somatosensory evoked potentials (SEP) were used to evaluate
      neurological functions. Transmission Electron Microscopy (TEM) was performed to
      investigate the change of NVU at the 28th day after modeling. Compared with the
      control group, the compression group shows a significant reduction (P < 0.05) of
      BBB score and a significant severity (P < 0.05) of abnormal SEP. TEM results of
      the compression group showed a striking increase in endothelial caveolae and
      vacuoles; a number of small spaces in tight junctions; a significant increase in
      pericyte processing area and vessel coverage; an expansion of the basement
      membrane region; swollen astrocyte endfeet and mitochondria; and the degeneration
      of neurons and axons. Our study revealed that damage to NVU components occurred
      followed by chronic compressive spinal cord injury. Several compensatory changes
      characterized by thicker endothelium, expansive BM, increased pericyte processing
      area and vessel coverage were also observed.

PMID- 29375329
TI  - Ventromedial Hypothalamus and the Generation of Aggression.
AB  - Aggression is a costly behavior, sometimes with severe consequences including
      death. Yet aggression is prevalent across animal species ranging from insects to
      humans, demonstrating its essential role in the survival of individuals and
      groups. The question of how the brain decides when to generate this costly
      behavior has intrigued neuroscientists for over a century and has led to the
      identification of relevant neural substrates. Various lesion and electric
      stimulation experiments have revealed that the hypothalamus, an ancient structure
      situated deep in the brain, is essential for expressing aggressive behaviors.
      More recently, studies using precise circuit manipulation tools have identified a
      small subnucleus in the medial hypothalamus, the ventrolateral part of the
      ventromedial hypothalamus (VMHvl), as a key structure for driving both aggression
      and aggression-seeking behaviors. Here, we provide an updated summary of the
      evidence that supports a role of the VMHvl in aggressive behaviors. We will
      consider our recent findings detailing the physiological response properties of
      populations of VMHvl cells during aggressive behaviors and provide new
      understanding regarding the role of the VMHvl embedded within the larger whole
      brain circuit for social sensation and action.

PMID- 29375332
TI  - Metacognitive Aspects of Executive Function Are Highly Associated with Social
      Functioning on Parent-Rated Measures in Children with Autism Spectrum Disorder.
AB  - Autism Spectrum Disorder (ASD) is characterized by social dysfunction. Even
      though executive dysfunction has been recognized as important in understanding
      ASD, the findings are inconsistent. This might be due to different definitions of
      executive function (EF), which part of EF that has been studied, structured vs.
      unstructured tasks, inclusion of different moderators (age, IQ, sex) and
      different diagnostic categories within the spectrum. The main finding is that
      people with ASD have more EF difficulties than normal controls and more
      difficulties on open-end tasks than on structured cognitive tasks. Since some EF
      difficulties may not be observable in a laboratory setting, informant measures
      might have higher ecological validity than neuropsychological tests. Evidence
      suggests that executive dysfunctions are associated with social impairments, but
      few studies have investigated the details of this relationship, and it remains
      unclear what types of EF deficits are relevant for the social problems of
      individuals with ASD. Here we investigated which EF domains were associated with
      various domains of social function on parent-rated measures. A total of 86
      children and adolescents with a diagnosis of ASD were included and tested for
      general cognitive abilities. Parents completed the Behavior Rating Inventory of
      Executive Function (BRIEF) and the Social Responsiveness Scale (SRS). Multiple
      regression analysis revealed significant associations between SRS scores and age,
      sex, total IQ and the BRIEF indexes. The Metacognition Index from the BRIEF added
      significantly to the prediction of the SRS total score and the subscales Social
      Communication, Social Motivation and Autistic Mannerisms. The findings suggest
      that metacognitive aspects of EF are of particular importance for social
      abilities in children and adolescents with ASD. Earlier research has shown that
      typically developing (TD) children have a different relationship between EF and
      social function than children with ASD. They found that in TD children the EF
      domain related to behavioral regulation was most important to social function.
      The results from the current study may have implications for understanding the
      cognitive components of the social problems that define ASD, and may be relevant
      in developing more targeted clinical EF interventions related to core ASD
      dysfunctions.

PMID- 29375333
TI  - Olanzapine Reverses MK-801-Induced Cognitive Deficits and Region-Specific
      Alterations of NMDA Receptor Subunits.
AB  - Cognitive dysfunction constitutes an essential component in schizophrenia for its
      early presence in the pathophysiology of the disease and close relatedness to
      life quality of patients. To develop effective treatment of cognitive deficits,
      it is important to understand their neurobiological causes and to identify
      potential therapeutic targets. In this study, adopting repeated MK-801 treatment
      as an animal model of schizophrenia, we investigated whether antipsychotic drugs,
      olanzapine and haloperidol, can reverse MK-801-induced cognitive deficits and how
      the reversal processes recruited proteins involved in glutamate neurotransmission
      in rat medial prefrontal cortex (mPFC) and hippocampus. We found that low-dose
      chronic MK-801 treatment impaired object-in-context recognition memory and
      reversal learning in the Morris water maze, leaving reference memory relatively
      unaffected, and that these cognitive deficits can be partially reversed by
      olanzapine, not haloperidol, treatment. At the molecular level, chronic MK-801
      treatment resulted in the reduction of multiple N-methyl-D-aspartate (NMDA)
      receptor subunits in rat mPFC and olanzapine, not haloperidol, treatment restored
      the levels of GluN1 and phosphorylated GluN2B in this region. Taken together, MK
      801-induced cognitive deficits may be associated with region-specific changes in
      NMDA receptor subunits and the reversal of specific NMDA receptor subunits may
      underlie the cognition-enhancing effects of olanzapine.

PMID- 29375334
TI  - Associative Agreement as a Predictor of Naming Ability in Alzheimer's Disease: A
      Case for the Semantic Nature of Associative Links.
AB  - We aimed to address the long-standing issue of the nature of the relationships
      that link a cue word to words associated with it. In keeping with a recently
      proposed neuropsychological model of semantic memory (Zannino et al., 2015), we
      provide support for the hypothesis that associative links are semantic in nature
      and not lexical. In support of this hypothesis, we demonstrate a relationship in
      healthy subjects between the probability of producing word X in response to cue
      word Y in a free association task and the probability of using word X to describe
      the meaning of word Y. Furthermore, we provide evidence that associative measures
      are altered in people suffering from Alzheimer's disease (AD) and predict their
      level of performance in a picture-naming task. We provide a parsimonious account
      of the experimental data gathered form these different sources of evidence
      according to the hypothesis that the links between a cue word and its associates
      can be viewed as binding a concept (the cue) to pieces of information regarding
      its meaning (the associates).

PMID- 29375335
TI  - Associations between Functional Connectivity Dynamics and BOLD Dynamics Are
      Heterogeneous Across Brain Networks.
AB  - Functional brain imaging has revealed two types of dynamic patterns of brain in
      the resting-state: the dynamics of spontaneous brain activities and the dynamics
      of functional interconnections between spontaneous brain activities. Although
      these two types of brain dynamics are usually investigated separately in the
      literature, recent functional magnetic resonance imaging (fMRI) studies have
      shown that they exhibit similar spatial patterns, suggesting the dynamics of
      spontaneous brain activities and the dynamics of their interconnections are
      associated with each other. In this study, we characterized the local blood
      oxygenation level dependent (BOLD) dynamics and the functional connectivity
      dynamics (FCD) in the resting-state, and then investigated their between-region
      associations. Time-varying FC was estimated as time-varying correlation
      coefficients using a sliding-window method, and the temporal variability of BOLD
      and time-varying FC were used to quantify the BOLD dynamics and the FCD,
      respectively. Our results showed that the BOLD dynamics and the FCD exhibit
      similar spatial patterns, and they are significantly associated across brain
      regions. Importantly, such associations are opposite for different types of FC
      (e.g., within-network FCD are negatively correlated with the BOLD dynamics but
      the between-network FCD are positively correlated with the BOLD dynamics), and
      they are spatially heterogeneous across brain networks. The identified
      heterogeneous associations between the BOLD dynamics and the FCD appear to convey
      related or even distinct information and might underscore the potential mechanism
      of brain coordination and co-evolution.

PMID- 29375336
TI  - The Cultivation of Pure Altruism via Gratitude: A Functional MRI Study of Change
      with Gratitude Practice.
AB  - Gratitude is an emotion and a trait linked to well-being and better health, and
      welcoming benefits to oneself is instrumentally valuable. However, theoretical
      and empirical work highlights that gratitude is more fully understood as an
      intrinsically valuable moral emotion. To understand the role of neural reward
      systems in the association between gratitude and altruistic motivations we tested
      two hypotheses: First, whether self-reported propensity toward gratitude relates
      to fMRI-derived indicators of "pure altruism," operationalized as the neural
      valuation of passive, private transfers to a charity versus to oneself. In young
      adult female participants, self-reported gratitude and altruism were associated
      with "neural pure altruism" in ventromedial prefrontal cortex (VMPFC) and nucleus
      accumbens. Second, whether neural pure altruism can be increased through
      practicing gratitude. In a double-blind study, we randomly assigned participants
      to either a gratitude-journal or active-neutral control journal group for 3
      weeks. Relative to pre-test levels, gratitude journaling increased the neural
      pure altruism response in the VMPFC. We posit that as a context-dependent value
      sensitive cortical region, the VMPFC supports change with gratitude practice, a
      change that is larger for benefits to others versus oneself.

PMID- 29375337
TI  - Quantification of Movement-Related EEG Correlates Associated with Motor Training:
      A Study on Movement-Related Cortical Potentials and Sensorimotor Rhythms.
AB  - The ability to learn motor tasks is important in both healthy and pathological
      conditions. Measurement tools commonly used to quantify the neurophysiological
      changes associated with motor training such as transcranial magnetic stimulation
      and functional magnetic resonance imaging pose some challenges, including safety
      concerns, utility, and cost. EEG offers an attractive alternative as a
      quantification tool. Different EEG phenomena, movement-related cortical
      potentials (MRCPs) and sensorimotor rhythms (event-related desynchronization-ERD,
      and event-related synchronization-ERS), have been shown to change with motor
      training, but conflicting results have been reported. The aim of this study was
      to investigate how the EEG correlates (MRCP and ERD/ERS) from the motor cortex
      are modulated by short (single session in 14 subjects) and long (six sessions in
      18 subjects) motor training. Ninety palmar grasps were performed before and after
      1 * 45 (or 6 * 45) min of motor training with the non-dominant hand (laparoscopic
      surgery simulation). Four channels of EEG were recorded continuously during the
      experiments. The MRCP and ERD/ERS from the alpha/mu and beta bands were
      calculated and compared before and after the training. An increase in the MRCP
      amplitude was observed after a single session of training, and a decrease was
      observed after six sessions. For the ERD/ERS analysis, a significant change was
      observed only after the single training session in the beta ERD. In conclusion,
      the MRCP and ERD change as a result of motor training, but they are subject to a
      marked intra- and inter-subject variability.

PMID- 29375338
TI  - Characteristics of Resting-State Functional Connectivity in Intractable
      Unilateral Temporal Lobe Epilepsy Patients with Impaired Executive Control
      Function.
AB  - Executive control function (ECF) deficit is a common complication of temporal
      lobe epilepsy (TLE). Characteristics of brain network connectivity in TLE with
      ECF dysfunction are still unknown. The aim of this study was to investigate
      resting-state functional connectivity (FC) changes in patients with unilateral
      intractable TLE with impaired ECF. Forty right-handed patients with left TLE
      confirmed by comprehensive preoperative evaluation and postoperative pathological
      findings were enrolled. The patients were divided into normal ECF (G1) and
      decreased ECF (G2) groups according to whether they showed ECF impairment on the
      Wisconsin Card Sorting Test (WCST). Twenty-three healthy volunteers were
      recruited as the healthy control (HC) group. All subjects underwent resting-state
      functional magnetic resonance imaging (rs-fMRI). Group-information-guided
      independent component analysis (GIG-ICA) was performed to estimate resting-state
      networks (RSNs) for all subjects. General linear model (GLM) was employed to
      analyze intra-network FC (p < 0.05, false discovery rate, FDR correction) and
      inter-network FC (p < 0.05, Bonferroni correction) of RSN among three groups.
      Pearson correlations between FC and neuropsychological tests were also determined
      through partial correlation analysis (p < 0.05). Eleven meaningful RSNs were
      identified from 40 left TLE and 23 HC subjects. Comparison of intra-network FC of
      all 11 meaningful RSNs did not reveal significant difference among the three
      groups (p > 0.05, FDR correction). For inter-network analysis, G2 exhibited
      decreased FC between the executive control network (ECN) and default-mode network
      (DMN) when compared with G1 (p = 0.000, Bonferroni correction) and HC (p = 0.000,
      Bonferroni correction). G1 showed no significant difference of FC between ECN and
      DMN when compared with HC. Furthermore, FC between ECN and DMN had significant
      negative correlation with perseverative responses (RP), response errors (RE) and
      perseverative errors (RPE) and had significant positive correlation categories
      completed (CC) in both G1 and G2 (p < 0.05). No significant difference of
      Montreal Cognitive Assessment (MoCA) was found between G1 and G2, while
      intelligence quotient (IQ) testing showed significant difference between G1and
      G2.There was no correlation between FC and either MoCA or IQ performance. Our
      findings suggest that ECF impairment in unilateral TLE is not confined to the
      diseased temporal lobe. Decreased FC between DMN and ECN may be an important
      characteristic of RSN in intractable unilateral TLE.

PMID- 29375339
TI  - Aberrant Functional Network Connectivity as a Biomarker of Generalized Anxiety
      Disorder.
AB  - Neural disruptions during emotion regulation are common of generalized anxiety
      disorder (GAD). Identifying distinct functional and effective connectivity
      patterns in GAD may provide biomarkers for their diagnoses. This study aims to
      investigate the differences of features of brain network connectivity between GAD
      patients and healthy controls (HC), and to assess whether those differences can
      serve as biomarkers to distinguish GAD from controls. Independent component
      analysis (ICA) with hierarchical partner matching (HPM-ICA) was conducted on
      resting-state functional magnetic resonance imaging data collected from 20 GAD
      patients with medicine-free and 20 matched HC, identifying nine highly
      reproducible and significantly different functional brain connectivity patterns
      across diagnostic groups. We then utilized Granger causality (GC) to study the
      effective connectivity between the regions that identified by HPM-ICA. The linear
      discriminant analysis was finally used to distinguish GAD from controls with
      these measures of neural connectivity. The GAD patients showed stronger
      functional connectivity in amygdala, insula, putamen, thalamus, and posterior
      cingulate cortex, but weaker in frontal and temporal cortex compared with
      controls. Besides, the effective connectivity in GAD was decreased from the
      cortex to amygdala and basal ganglia. Applying the ICA and GC features to the
      classifier led to a classification accuracy of 87.5%, with a sensitivity of 90.0%
      and a specificity of 85.0%. These findings suggest that the presence of emotion
      dysregulation circuits may contribute to the pathophysiology of GAD, and these
      aberrant brain features may serve as robust brain biomarkers for GAD.

PMID- 29375340
TI  - Motor Imagery as a Function of Disease Severity in Multiple Sclerosis: An fMRI
      Study.
AB  - Motor imagery (MI) is defined as mental execution without any actual movement.
      While healthy adults usually show temporal equivalence, i.e., isochrony, between
      the mental simulation of an action and its actual performance, neurological
      disorders are associated with anisochrony. Unlike in patients with stroke and
      Parkinson disease, only a few studies have investigated differences of MI ability
      in multiple sclerosis (MS). However, the relationship among disease severity,
      anisochrony and brain activation patterns during MI has not been investigated
      yet. Here, we propose to investigate MI in MS patients using fMRI during a
      behavioral task executed with dominant/non-dominant hand and to evaluate whether
      anisochrony is associated with disease severity. Thirty-seven right-handed MS
      patients, 17 with clinically isolated syndrome (CIS) suggestive of MS and 20 with
      relapsing-remitting MS (RR-MS) and 20 right-handed healthy controls (HC)
      underwent fMRI during a motor task consisting in the actual or imaged movement of
      squeezing a foam ball with the dominant and non-dominant hand. The same tasks
      were performed outside the MRI room to record the number of actual and imagined
      ball squeezes, and calculate an Index of performance (IP) based on the ratio
      between actual and imagined movements. IP showed that a progressive loss of
      ability in simulating actions (i.e., anisochrony) more pronounced for non
      dominant hand, was found as function of the disease course. Moreover, anisochrony
      was associated with activation of occipito-parieto-frontal areas that were more
      extensive at the early stages of the disease, probably in order to counteract the
      changes due to MS. However, the neural engagement of compensatory brain areas
      becomes more difficult with more challenging tasks, i.e., dominant vs. non
      dominant hand, with a consequent deficit in behavioral performance. These results
      show a strict association between MI performance and disease severity, suggesting
      that, at early stages of the disease, anisochrony in MI could be considered as
      surrogate behavioral marker of MS severity.

PMID- 29375341
TI  - Functional Connectivity Alterations between Networks and Associations with Infant
      Immune Health within Networks in HIV Infected Children on Early Treatment: A
      Study at 7 Years.
AB  - Although HIV has been shown to impact brain connectivity in adults and youth, it
      is not yet known to what extent long-term early antiretroviral therapy (ART) may
      alter these effects, especially during rapid brain development in early
      childhood. Using both independent component analysis (ICA) and seed-based
      correlation analysis (SCA), we examine the effects of HIV infection in
      conjunction with early ART on resting state functional connectivity (FC) in 7
      year old children. HIV infected (HIV+) children were from the Children with HIV
      Early Antiretroviral Therapy (CHER) trial and all initiated ART before 18 months;
      uninfected children were recruited from an interlinking vaccine trial. To better
      understand the effects of current and early immune health on the developing
      brain, we also investigated among HIV+ children the association of FC at 7 years
      with CD4 count and CD4%, both in infancy (6-8 weeks) and at scan. Although we
      found no differences within any ICA-generated resting state networks (RSNs)
      between HIV+ and uninfected children (27 HIV+, 18 uninfected), whole brain
      connectivity to seeds located at RSN connectivity peaks revealed several loci of
      FC differences, predominantly from seeds in midline regions (posterior cingulate
      cortex, paracentral lobule, cuneus, and anterior cingulate). Reduced long-range
      connectivity and increased short-range connectivity suggest developmental delay.
      Within the HIV+ children, clinical measures at age 7 years were not associated
      with FC values in any of the RSNs; however, poor immune health during infancy was
      associated with localized FC increases in the somatosensory, salience and basal
      ganglia networks. Together these findings suggest that HIV may affect brain
      development from its earliest stages and persist into childhood, despite early
      ART.

PMID- 29375342
TI  - Allostatic Load Is Linked to Cortical Thickness Changes Depending on Body-Weight
      Status.
AB  - Objective: Overweight (body mass index or BMI >= 25 kg/m2) and stress interact
      with each other in complex ways. Overweight promotes chronic low-inflammation
      states, while stress is known to mediate caloric intake. Both conditions are
      linked to several avoidable health problems and to cognitive decline, brain
      atrophy, and dementia. Since it was proposed as a framework for the onset of
      mental illness, the allostatic load model has received increasing attention.
      Although changes in health and cognition related to overweight and stress are
      well-documented separately, the association between allostatic load and brain
      integrity has not been addressed in depth, especially among overweight subjects.
      Method: Thirty-four healthy overweight-to-obese and 29 lean adults underwent
      blood testing, neuropsychological examination, and magnetic resonance imaging to
      assess the relationship between cortical thickness and allostatic load,
      represented as an index of 15 biomarkers (this is, systolic and diastolic
      arterial tension, glycated hemoglobin, glucose, creatinine, total cholesterol,
      HDL and LDL cholesterol, triglycerides, c-reactive protein, interleukin-6,
      insulin, cortisol, fibrinogen, and leptin). Results: Allostatic load indexes
      showed widespread positive and negative significant correlations (p < 0.01) with
      cortical thickness values depending on body-weight status. Conclusion: The
      increase of allostatic load is linked to changes in the gray matter composition
      of regions monitoring behavior, sensory-reward processing, and general cognitive
      function.

PMID- 29375343
TI  - A Novel Early Diagnosis System for Mild Cognitive Impairment Based on Local
      Region Analysis: A Pilot Study.
AB  - Alzheimer's disease (AD) is an irreversible neurodegenerative disorder that
      accounts for 60-70% of cases of dementia in the elderly. An early diagnosis of AD
      is usually hampered for many reasons including the variable clinical and
      pathological features exhibited among affected individuals. This paper presents a
      computer-aided diagnosis (CAD) system with the primary goal of improving the
      accuracy, specificity, and sensitivity of diagnosis. In this system, PiB-PET
      scans, which were obtained from the ADNI database, underwent five essential
      stages. First, the scans were standardized and de-noised. Second, an Automated
      Anatomical Labeling (AAL) atlas was utilized to partition the brain into 116
      regions or labels that served for local (region-based) diagnosis. Third, scale
      invariant Laplacian of Gaussian (LoG) was used, per brain label, to detect the
      discriminant features. Fourth, the regions' features were analyzed using a
      general linear model in the form of a two-sample t-test. Fifth, the support
      vector machines (SVM) and their probabilistic variant (pSVM) were constructed to
      provide local, followed by global diagnosis. The system was evaluated on scans of
      normal control (NC) vs. mild cognitive impairment (MCI) (19 NC and 65 MCI scans).
      The proposed system showed superior accuracy, specificity, and sensitivity as
      compared to other related work.

PMID- 29375344
TI  - Self-guided Positive Imagery Training: Effects beyond the Emotions-A Loreta
      Study.
AB  - Previously we demonstrated that a 12-week lasting self-guided positive imagery
      training had a positive effect on the psycho-emotional state of healthy subjects
      and was associated with an increase in functional connectivity in the brain. Here
      we repeated the previous project, but expanded the study, testing the hypothesis
      that training can also affect cognitive functions. Twenty subjects (half of them
      with subthreshold depression according CES-D) participated in the program of
      positive imagery training for 12 weeks. The schedule began with group training
      for 2 days, followed by training at home. Evaluations of cognitive functions and
      electroencephalographic (EEG) activity were conducted during three examinations
      as follows: E0-baseline (1 month before the training); E1-pre-training and E2
      post-training. CNS Vital Signs battery was used to test the following cognitive
      domains: verbal and visual memory, executive functions, cognitive flexibility,
      social acuity, non-verbal reasoning. EEGs (19-channel) were recorded at rest with
      closed eyes and analyzed with Low-resolution electromagnetic tomography software.
      One-way repeated measures ANOVA, followed by pairwise comparison showed a
      significant increase after training (E2 vs. E1; E2 vs. E0) in the number of
      correct hits for positive emotions received during perception of emotions test
      (POET); after the sample was split according to the initial presence of
      depressive symptoms, the effect was present only in the subgroup with
      subthreshold depressive symptomatology. Post-training (E2 vs. E1; E2 vs. E0) the
      number of correct answers on non-verbal reasoning test increased; this effect was
      observed only in the subgroup that does have any depressive symptoms. Comparison
      of EEG post-training vs. pre-training demonstrated a significant reduction in
      current source density (CSD) after the training in the left hemisphere (insular
      cortex, frontal and temporal lobes in delta, theta and alpha1 bands). The
      observed changes were presented only in the subgroup with initial subthreshold
      depressive symptomatology. A negative correlation was found between POET and CSD
      in the left insular cortex for theta band. No significant differences were
      observed when data from EEG and cognitive tests obtained during pre-training were
      compared with baseline values. Potential use of training for the rehabilitation
      of various disturbances with cognitive and emotional deficits is discussed.

PMID- 29375345
TI  - Melatonin Secretion during a Short Nap Fosters Subsequent Feedback Learning.
AB  - Sleep helps to protect and renew hippocampus-dependent declarative learning. Less
      is known about forms of learning that mainly engage the dopaminergic reward
      system. Animal studies showed that exogenous melatonin modulates the responses of
      the dopaminergic reward system and acts as a neuroprotectant promoting memory. In
      humans, melatonin is mainly secreted in darkness during evening hours supporting
      sleep. In this study, we investigate the effects of a short period of daytime
      sleep (nap) and endogenous melatonin on reward learning. Twenty-seven healthy,
      adult students took part in an experiment, either taking a 90-min afternoon nap
      or watching videos (within-subject design). Before and after the sleep vs. wake
      interval, saliva melatonin levels and reward learning were measured, and in the
      nap condition, a polysomnogram was obtained. Reward learning was assessed using a
      two-alternative probabilistic reinforcement-learning task. Sleep itself and
      subjective arousal or valence had no significant effects on reward learning.
      However, this study showed for the first time that an afternoon nap can elicit a
      small but significant melatonin response in about 41% of the participants and
      that the magnitude of the melatonin response predicts subsequent reward learning.
      Only in melatonin responders did a short nap improve reward learning. The
      difference between melatonin-responders and non-responders occurred very early
      during learning indicating that melatonin might have improved working memory
      rather than reward learning. Future studies should use paradigms differentiating
      working memory and reward learning to clarify which aspect of human feedback
      learning might profit from melatonin.

PMID- 29375346
TI  - Modulating Spatial Processes and Navigation via Transcranial Electrical
      Stimulation: A Mini Review.
AB  - Transcranial electrical stimulation (tES) uses low intensity current to alter
      neuronal activity in superficial cortical regions, and has gained popularity as a
      tool for modulating several aspects of perception and cognition. This mini-review
      article provides an overview of tES and its potential for modulating spatial
      processes underlying successful navigation, including spatial attention, spatial
      perception, mental rotation and visualization. Also considered are recent
      advances in empirical research and computational modeling elucidating several
      stable cortical-subcortical networks with dynamic involvement in spatial
      processing and navigation. Leveraging these advances may prove valuable for using
      tES, particularly transcranial direct and alternating current stimulation
      (tDCS/tACS), to indirectly target subcortical brain regions by altering neuronal
      activity in distant yet functionally connected cortical areas. We propose future
      research directions to leverage these advances in human neuroscience.

PMID- 29375347
TI  - The Effects of Theta and Gamma tACS on Working Memory and Electrophysiology.
AB  - A single blind sham-controlled study was conducted to explore the effects of
      theta and gamma transcranial alternating current stimulation (tACS) on offline
      performance on working memory tasks. In order to systematically investigate how
      specific parameters of tACS affect working memory, we manipulated the frequency
      of stimulation (theta frequency vs. gamma frequency), the type of task (n-back
      vs. change detection task) and the content of the tasks (verbal vs. figural
      stimuli). A repeated measures design was used that consisted of three sessions:
      theta tACS, gamma tACS and sham tACS. In total, four experiments were conducted
      which differed only with respect to placement of tACS electrodes (bilateral
      frontal, bilateral parietal, left fronto-parietal and right-fronto parietal).
      Healthy female students (N = 72) were randomly assigned to one of these groups,
      hence we were able to assess the efficacy of theta and gamma tACS applied over
      different brain areas, contrasted against sham stimulation. The pre-post/sham
      resting electroencephalogram (EEG) analysis showed that theta tACS significantly
      affected theta amplitude, whereas gamma tACS had no significant effect on EEG
      amplitude in any of the frequency bands of interest. Gamma tACS did not
      significantly affect working memory performance compared to sham, and theta tACS
      led to inconsistent changes in performance on the n-back tasks. Active theta tACS
      significantly affected P3 amplitude and latency during performance on the n-back
      tasks in the bilateral parietal and right-fronto parietal protocols.

PMID- 29375348
TI  - Linear Representation of Emotions in Whole Persons by Combining Facial and Bodily
      Expressions in the Extrastriate Body Area.
AB  - Our human brain can rapidly and effortlessly perceive a person's emotional state
      by integrating the isolated emotional faces and bodies into a whole. Behavioral
      studies have suggested that the human brain encodes whole persons in a holistic
      rather than part-based manner. Neuroimaging studies have also shown that body
      selective areas prefer whole persons to the sum of their parts. The body
      selective areas played a crucial role in representing the relationships between
      emotions expressed by different parts. However, it remains unclear in which
      regions the perception of whole persons is represented by a combination of faces
      and bodies, and to what extent the combination can be influenced by the whole
      person's emotions. In the present study, functional magnetic resonance imaging
      data were collected when participants performed an emotion distinction task.
      Multi-voxel pattern analysis was conducted to examine how the whole person-evoked
      responses were associated with the face- and body-evoked responses in several
      specific brain areas. We found that in the extrastriate body area (EBA), the
      whole person patterns were most closely correlated with weighted sums of face and
      body patterns, using different weights for happy expressions but equal weights
      for angry and fearful ones. These results were unique for the EBA. Our findings
      tentatively support the idea that the whole person patterns are represented in a
      part-based manner in the EBA, and modulated by emotions. These data will further
      our understanding of the neural mechanism underlying perceiving emotional
      persons.

PMID- 29375349
TI  - Correlation of BOLD Signal with Linear and Nonlinear Patterns of EEG in Resting
      State EEG-Informed fMRI.
AB  - Concurrent EEG and fMRI acquisitions in resting state showed a correlation
      between EEG power in various bands and spontaneous BOLD fluctuations. However,
      there is a lack of data on how changes in the complexity of brain dynamics
      derived from EEG reflect variations in the BOLD signal. The purpose of our study
      was to correlate both spectral patterns, as linear features of EEG rhythms, and
      nonlinear EEG dynamic complexity with neuronal activity obtained by fMRI. We
      examined the relationships between EEG patterns and brain activation obtained by
      simultaneous EEG-fMRI during the resting state condition in 25 healthy right
      handed adult volunteers. Using EEG-derived regressors, we demonstrated a
      substantial correlation of BOLD signal changes with linear and nonlinear features
      of EEG. We found the most significant positive correlation of fMRI signal with
      delta spectral power. Beta and alpha spectral features had no reliable effect on
      BOLD fluctuation. However, dynamic changes of alpha peak frequency exhibited a
      significant association with BOLD signal increase in right-hemisphere areas.
      Additionally, EEG dynamic complexity as measured by the HFD of the 2-20 Hz EEG
      frequency range significantly correlated with the activation of cortical and
      subcortical limbic system areas. Our results indicate that both spectral features
      of EEG frequency bands and nonlinear dynamic properties of spontaneous EEG are
      strongly associated with fluctuations of the BOLD signal during the resting state
      condition.

PMID- 29375350
TI  - Sex Differences in Categorical Adaptation for Faces and Chinese Characters during
      Early Perceptual Processing.
AB  - Previous event-related potential studies support sex differences in the N170
      response during face and word processing; however, it remains unclear whether
      N170 categorical adaptation for faces and words is different between women and
      men. Using an adaptation paradigm, in which an adaptor and subsequent test
      stimulus are presented during each trial, the present study investigated N170
      categorical adaptation for faces and Chinese characters in both women and men.
      The results demonstrated that the N170 amplitude elicited by test stimuli in
      within-category condition was lower than in control category condition, and this
      was observed during both face and Chinese character processing in women and men.
      In addition, we found that men have greater N170 categorical adaptation for face
      and word processing than women. There was also a significant correlation between
      N170 categorical adaptation indices for face and Chinese character processing in
      men, which did not occur in women. These findings suggest that men and women
      process repeated faces or words differently.

PMID- 29375351
TI  - Neural Correlates of Response Inhibition and Conflict Control on Facial
      Expressions.
AB  - Response inhibition and conflict control on affective information can be regarded
      as two important emotion regulation and cognitive control processes. The
      emotional Go/Nogo flanker paradigm was adopted and participant's event-related
      potentials (ERPs) were analyzed to investigate how response inhibition and
      conflict control interplayed. The behavioral findings revealed that participants
      showed higher accuracy to identify happy faces in congruent condition relative to
      that in incongruent condition. The electrophysiological results manifested that
      response inhibition and conflict control interplayed during the
      detection/conflict monitoring stage, and Nogo-N2 was more negative in the
      incongruent trials than the congruent trials. With regard to the inhibitory
      control/conflict resolution stage, Nogo responses induced greater frontal P3 and
      parietal P3 responses than Go responses did. The difference waveforms of N2 and
      parietal P3 showed that response inhibition and conflict control had distinct
      processes, and the multiple responses requiring both conflict control and
      response inhibition processes induced stronger monitoring and resolution
      processes than conflict control. The current study manifested that response
      inhibition and conflict control on emotional information required separable
      neural mechanisms during emotion regulation processes.

PMID- 29375352
TI  - Two Different Populations within the Healthy Elderly: Lack of Conflict Detection
      in Those at Risk of Cognitive Decline.
AB  - During healthy aging, inhibitory processing is affected at the sensorial,
      perceptual, and cognitive levels. The assessment of event-related potentials
      (ERPs) during the Stroop task has been used to study age-related decline in the
      efficiency of inhibitory processes. Studies using ERPs have found that the P300
      amplitude increases and the N500 amplitude is attenuated in healthy elderly
      adults compared to those in young adults. On the other hand, it has been reported
      that theta excess in resting EEG with eyes closed is a good predictor of
      cognitive decline during aging 7 years later, while a normal EEG increases the
      probability of not developing cognitive decline. The behavioral and ERP responses
      during a Counting-Stroop task were compared between 22 healthy elderly subjects
      with normal EEG (Normal-EEG group) and 22 healthy elderly subjects with an excess
      of EEG theta activity (Theta-EEG group). Behaviorally, the Normal-EEG group
      showed a higher behavioral interference effect than the Theta-EEG group. ERP
      patterns were different between the groups, and two facts are highlighted: (a)
      the P300 amplitude was higher in the Theta-EEG group, with both groups showing a
      P300 effect in almost all electrodes, and (b) the Theta-EEG group did not show an
      N500 effect. These results suggest that the diminishment in inhibitory control
      observed in the Theta-EEG group may be compensated by different processes in
      earlier stages, which would allow them to perform the task with similar
      efficiency to that of participants with a normal EEG. This study is the first to
      show that healthy elderly subjects with an excess of theta EEG activity not only
      are at risk of developing cognitive decline but already have a cognitive
      impairment.

PMID- 29375353
TI  - Positive Classification Advantage: Tracing the Time Course Based on Brain
      Oscillation.
AB  - The present study aimed to explore the modulation of frequency bands (alpha,
      beta, theta) underlying the positive facial expressions classification advantage
      within different post-stimulus time intervals (100-200 ms, 200-300 ms, 300-400
      ms). For this purpose, we recorded electroencephalogram (EEG) activity during an
      emotion discrimination task for happy, sad and neutral faces. The correlation
      between the non-phase-locked power of frequency bands and reaction times (RTs)
      was assessed. The results revealed that beta played a major role in positive
      classification advantage (PCA) within the 100-200 and 300-400 ms intervals,
      whereas theta was important within the 200-300 ms interval. We propose that the
      beta band modulated the neutral and emotional face classification process, and
      that the theta band modulated for happy and sad face classification.

PMID- 29375354
TI  - The Increased Sex Differences in Susceptibility to Emotional Stimuli during
      Adolescence: An Event-Related Potential Study.
AB  - The present study investigated how pubertal development and sex interact to
      influence humans' emotion susceptibility during adolescence. Event-related
      potentials were recorded for highly emotional, mildly emotional and neutral
      stimuli in positive and negative blocks, when 73 adolescents (36 pre-/early
      pubertal students, 19 boys, 10-12 years old; 37 mid-/late pubertal students, 18
      boys, 11-13 years old) performed an implicit emotion task. Behavioral analysis
      showed higher positive mood ratings for pre-/early compared to mid-/late pubertal
      subjects, irrespective of sex and block. ERP analysis demonstrated increasing
      Late Positive Potential (LPP) amplitudes from neutral, Mildly Positive (MP) to
      Highly Positive (HP) stimuli in pre-/early pubertal, but not in mid-/late
      pubertal adolescents. However, girls exhibited higher P3a amplitudes during mid
      /late relative to pre-/early puberty for negative stimuli irrespective of
      intensity; while this puberty effect was absent in boys. In addition, girls
      compared to boys exhibited a more pronounced LPP enhancement effect for Highly
      Negative (HN) stimuli and a lower threshold of responding to negative stimuli in
      P3b amplitudes, regardless of puberty. These results suggest that, though there
      is a puberty-independent sensitivity to negative stimuli in girls relative to
      boys, puberty selectively intensifies girls' attention bias for negative stimuli
      and reduces experiential sensitivity to positive stimuli in both sexes. The
      implication of these results for the sex-related psychopathology during
      adolescence were discussed.

PMID- 29375356
TI  - Classification of Alzheimer's Disease, Mild Cognitive Impairment, and Cognitively
      Unimpaired Individuals Using Multi-feature Kernel Discriminant Dictionary
      Learning.
AB  - Accurate classification of either patients with Alzheimer's disease (AD) or
      patients with mild cognitive impairment (MCI), the prodromal stage of AD, from
      cognitively unimpaired (CU) individuals is important for clinical diagnosis and
      adequate intervention. The current study focused on distinguishing AD or MCI from
      CU based on the multi-feature kernel supervised within-Class-similar
      discriminative dictionary learning algorithm (MKSCDDL), which we introduced in a
      previous study, demonstrating that MKSCDDL had superior performance in face
      recognition. Structural magnetic resonance imaging (sMRI), fluorodeoxyglucose
      (FDG) positron emission tomography (PET), and florbetapir-PET data from the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) database were all included for
      classification of AD vs. CU, MCI vs. CU, as well as AD vs. MCI (113 AD patients,
      110 MCI patients, and 117 CU subjects). By adopting MKSCDDL, we achieved a
      classification accuracy of 98.18% for AD vs. CU, 78.50% for MCI vs. CU, and
      74.47% for AD vs. MCI, which in each instance was superior to results obtained
      using several other state-of-the-art approaches (MKL, JRC, mSRC, and mSCDDL). In
      addition, testing time results outperformed other high quality methods.
      Therefore, the results suggested that the MKSCDDL procedure is a promising tool
      for assisting early diagnosis of diseases using neuroimaging data.

PMID- 29375357
TI  - Image Processing for Bioluminescence Resonance Energy Transfer Measurement-BRET
      Analyzer.
AB  - A growing number of tools now allow live recordings of various signaling pathways
      and protein-protein interaction dynamics in time and space by ratiometric
      measurements, such as Bioluminescence Resonance Energy Transfer (BRET) Imaging.
      Accurate and reproducible analysis of ratiometric measurements has thus become
      mandatory to interpret quantitative imaging. In order to fulfill this necessity,
      we have developed an open source toolset for Fiji-BRET-Analyzer-allowing a
      systematic analysis, from image processing to ratio quantification. We share this
      open source solution and a step-by-step tutorial at
      https://github.com/ychastagnier/BRET-Analyzer. This toolset proposes (1) image
      background subtraction, (2) image alignment over time, (3) a composite
      thresholding method of the image used as the denominator of the ratio to refine
      the precise limits of the sample, (4) pixel by pixel division of the images and
      efficient distribution of the ratio intensity on a pseudocolor scale, and (5)
      quantification of the ratio mean intensity and standard variation among pixels in
      chosen areas. In addition to systematize the analysis process, we show that the
      BRET-Analyzer allows proper reconstitution and quantification of the ratiometric
      image in time and space, even from heterogeneous subcellular volumes. Indeed,
      analyzing twice the same images, we demonstrate that compared to standard
      analysis BRET-Analyzer precisely define the luminescent specimen limits,
      enlightening proficient strengths from small and big ensembles over time. For
      example, we followed and quantified, in live, scaffold proteins interaction
      dynamics in neuronal sub-cellular compartments including dendritic spines, for
      half an hour. In conclusion, BRET-Analyzer provides a complete, versatile and
      efficient toolset for automated reproducible and meaningful image ratio analysis.

PMID- 29375358
TI  - Dynamic Hebbian Cross-Correlation Learning Resolves the Spike Timing Dependent
      Plasticity Conundrum.
AB  - Spike Timing-Dependent Plasticity has been found to assume many different forms.
      The classic STDP curve, with one potentiating and one depressing window, is only
      one of many possible curves that describe synaptic learning using the STDP
      mechanism. It has been shown experimentally that STDP curves may contain multiple
      LTP and LTD windows of variable width, and even inverted windows. The underlying
      STDP mechanism that is capable of producing such an extensive, and apparently
      incompatible, range of learning curves is still under investigation. In this
      paper, it is shown that STDP originates from a combination of two dynamic Hebbian
      cross-correlations of local activity at the synapse. The correlation of the
      presynaptic activity with the local postsynaptic activity is a robust and
      reliable indicator of the discrepancy between the presynaptic neuron and the
      postsynaptic neuron's activity. The second correlation is between the local
      postsynaptic activity with dendritic activity which is a good indicator of
      matching local synaptic and dendritic activity. We show that this simple time
      independent learning rule can give rise to many forms of the STDP learning curve.
      The rule regulates synaptic strength without the need for spike matching or other
      supervisory learning mechanisms. Local differences in dendritic activity at the
      synapse greatly affect the cross-correlation difference which determines the
      relative contributions of different neural activity sources. Dendritic activity
      due to nearby synapses, action potentials, both forward and back-propagating, as
      well as inhibitory synapses will dynamically modify the local activity at the
      synapse, and the resulting STDP learning rule. The dynamic Hebbian learning rule
      ensures furthermore, that the resulting synaptic strength is dynamically stable,
      and that interactions between synapses do not result in local instabilities. The
      rule clearly demonstrates that synapses function as independent localized
      computational entities, each contributing to the global activity, not in a simply
      linear fashion, but in a manner that is appropriate to achieve local and global
      stability of the neuron and the entire dendritic structure.

PMID- 29375355
TI  - Computational Foundations of Natural Intelligence.
AB  - New developments in AI and neuroscience are revitalizing the quest to
      understanding natural intelligence, offering insight about how to equip machines
      with human-like capabilities. This paper reviews some of the computational
      principles relevant for understanding natural intelligence and, ultimately,
      achieving strong AI. After reviewing basic principles, a variety of computational
      modeling approaches is discussed. Subsequently, I concentrate on the use of
      artificial neural networks as a framework for modeling cognitive processes. This
      paper ends by outlining some of the challenges that remain to fulfill the promise
      of machines that show human-like intelligence.

PMID- 29375359
TI  - Toward an Improvement of the Analysis of Neural Coding.
AB  - Machine learning and artificial intelligence have strong roots on principles of
      neural computation. Some examples are the structure of the first perceptron,
      inspired in the retina, neuroprosthetics based on ganglion cell recordings or
      Hopfield networks. In addition, machine learning provides a powerful set of tools
      to analyze neural data, which has already proved its efficacy in so distant
      fields of research as speech recognition, behavioral states classification, or
      LFP recordings. However, despite the huge technological advances in neural data
      reduction of dimensionality, pattern selection, and clustering during the last
      years, there has not been a proportional development of the analytical tools used
      for Time-Frequency (T-F) analysis in neuroscience. Bearing this in mind, we
      introduce the convenience of using non-linear, non-stationary tools, EMD
      algorithms in particular, for the transformation of the oscillatory neural data
      (EEG, EMG, spike oscillations...) into the T-F domain prior to its analysis with
      machine learning tools. We support that to achieve meaningful conclusions, the
      transformed data we analyze has to be as faithful as possible to the original
      recording, so that the transformations forced into the data due to restrictions
      in the T-F computation are not extended to the results of the machine learning
      analysis. Moreover, bioinspired computation such as brain-machine interface may
      be enriched from a more precise definition of neuronal coding where non
      linearities of the neuronal dynamics are considered.

PMID- 29375360
TI  - Improving Fine Control of Grasping Force during Hand-Object Interactions for a
      Soft Synergy-Inspired Myoelectric Prosthetic Hand.
AB  - The concept of postural synergies of the human hand has been shown to potentially
      reduce complexity in the neuromuscular control of grasping. By merging this
      concept with soft robotics approaches, a multi degrees of freedom soft-synergy
      prosthetic hand [SoftHand-Pro (SHP)] was created. The mechanical innovation of
      the SHP enables adaptive and robust functional grasps with simple and intuitive
      myoelectric control from only two surface electromyogram (sEMG) channels.
      However, the current myoelectric controller has very limited capability for fine
      control of grasp forces. We addressed this challenge by designing a hybrid-gain
      myoelectric controller that switches control gains based on the sensorimotor
      state of the SHP. This controller was tested against a conventional single-gain
      (SG) controller, as well as against native hand in able-bodied subjects. We used
      the following tasks to evaluate the performance of grasp force control: (1) pick
      and place objects with different size, weight, and fragility levels using power
      or precision grasp and (2) squeezing objects with different stiffness. Sensory
      feedback of the grasp forces was provided to the user through a non-invasive,
      mechanotactile haptic feedback device mounted on the upper arm. We demonstrated
      that the novel hybrid controller enabled superior task completion speed and fine
      force control over SG controller in object pick-and-place tasks. We also found
      that the performance of the hybrid controller qualitatively agrees with the
      performance of native human hands.

PMID- 29375362
TI  - Age-Modulated Associations between KIBRA, Brain Volume, and Verbal Memory among
      Healthy Older Adults.
AB  - The resource modulation hypothesis suggests that the influence of genes on
      cognitive functioning increases with age. The KIBRA single nucleotide
      polymorphism rs17070145, associated with episodic memory and working memory, has
      been suggested to follow such a pattern, but few studies have tested this
      assertion directly. The present study investigated the relationship between KIBRA
      alleles (T carriers vs. CC homozygotes), cognitive performance, and brain volumes
      in three groups of cognitively healthy adults-middle aged (ages 52-64, n = 38),
      young old (ages 65-72, n = 45), and older old (ages 73-92, n = 62)-who were
      carefully matched on potentially confounding variables including apolipoprotein
      epsilon4 status and hypertension. Consistent with our prediction, T carriers
      maintained verbal memory performance with increasing age while CC homozygotes
      declined. Voxel-based morphometric analysis of magnetic resonance images showed
      an advantage for T carriers in frontal white matter volume that increased with
      age. Focusing on the older old group, this advantage for T carriers was also
      evident in left lingual gyrus gray matter and several additional frontal white
      matter regions. Contrary to expectations, neither KIBRA nor the interaction
      between KIBRA and age predicted hippocampal volumes. None of the brain regions
      investigated showed a CC homozygote advantage. Taken together, these data suggest
      that KIBRA results in decreased verbal memory performance and lower brain volumes
      in CC homozygotes compared to T carriers, particularly among the oldest old,
      consistent with the resource modulation hypothesis.

PMID- 29375361
TI  - Salience Network and Depressive Severities in Parkinson's Disease with Mild
      Cognitive Impairment: A Structural Covariance Network Analysis.
AB  - Purpose: In Parkinson's disease with mild cognitive impairment (PD-MCI), we
      investigated the clinical significance of salience network (SN) in depression and
      cognitive performance. Methods: Seventy seven PD-MCI patients that fulfilled
      multi-domain and non-amnestic subtype were included. Gray matter structural
      covariance networks were constructed by 3D T1-magnetic resonance imaging and seed
      based analysis. The patients were divided into two groups by psychiatric
      interviews and screening of Geriatric Depression Scale (GDS): PD-MCI with
      depression (PD-MCI-D) or without depression (PD-MCI-ND). The seed or peak cluster
      volume, or the significant differences in the regression slopes in each seed-peak
      cluster correlation, were used to evaluate the significance with the
      neurobehavioral scores. Results: This study is the first to demonstrate that the
      PD-MCI-ND group presented a larger number of voxels of structural covariance in
      SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak
      cluster of left lingual gyrus showed significant inverse correlation with the
      Geriatric Depression Scale (GDS; r = -0.231, P = 0.046). Conclusions: This study
      is the first to validate the clinical significance of the SN in PD-MCI-D. The
      right insular seed value and the SN correlated with the severity of depression in
      PD-MCI.

PMID- 29375363
TI  - Physiological Aging Influence on Brain Hemodynamic Activity during Task
      Switching: A fNIRS Study.
AB  - Task-switching (TS) paradigm is a well-known validated tool useful for exploring
      the neural substrates of cognitive control, in particular the activity of the
      lateral and medial prefrontal cortex. This work is aimed at investigating how
      physiological aging influences hemodynamic response during the execution of a
      color-shape TS paradigm. A multi-channel near infrared spectroscopy (fNIRS) was
      used to measure hemodynamic activity in 27 young (30.00 +/- 7.90 years) and 11
      elderly participants (57.18 +/- 9.29 years) healthy volunteers (55% male, age
      range: (19-69) years) during the execution of a TS paradigm. Two holders were
      placed symmetrically over the left/right hemispheres to record cortical activity
      [oxy-(HbO) and deoxy-hemoglobin (HbR) concentration] of the dorso-lateral
      prefrontal cortex (DLPFC), the dorsal premotor cortex (PMC), and the dorso-medial
      part of the superior frontal gyrus (sFG). TS paradigm requires participants to
      repeat the same task over a variable number of trials, and then to switch to a
      different task during the trial sequence. A two-sample t-test was carried out to
      detect differences in cortical responses between groups. Multiple linear
      regression analysis was used to evaluate the impact of age on the prefrontal
      neural activity. Elderly participants were significantly slower than young
      participants in both color- (p < 0.01, t = -3.67) and shape-single tasks (p =
      0.026, t = -2.54) as well as switching (p = 0.026, t = -2.41) and repetition
      trials (p = 0.012, t = -2.80). Differences in cortical activation between groups
      were revealed for HbO mean concentration of switching task in the PMC (p = 0.048,
      t = 2.94). In the whole group, significant increases of behavioral performance
      were detected in switching trials, which positively correlated with aging.
      Multivariate regression analysis revealed that the HbO mean concentration of
      switching task in the PMC (p = 0.01, beta = -0.321) and of shape single-task in
      the sFG (p = 0.003, beta = 0.342) were the best predictors of age effects. Our
      findings demonstrated that TS might be a reliable instrument to gather a measure
      of cognitive resources in older people. Moreover, the fNIRS-related brain
      activity extracted from frontoparietal cortex might become a useful indicator of
      aging effects.

PMID- 29375364
TI  - Disparate Effects of Lithium and a GSK-3 Inhibitor on Neuronal Oscillatory
      Activity in Prefrontal Cortex and Hippocampus.
AB  - Glycogen synthase kinase-3 (GSK-3) plays a critical role in cognitive dysfunction
      associated with Alzheimer's disease (AD), yet the mechanism by which GSK-3 alters
      cognitive processes in other disorders, such as schizophrenia, remains unknown.
      In the present study, we demonstrated a role for GSK-3 in the direct regulation
      of neuronal oscillations in hippocampus (HIP) and prelimbic cortex (PL). A
      comparison of the GSK-3 inhibitors SB 216763 and lithium demonstrated disparate
      effects of the drugs on spatial memory and neural oscillatory activity in HIP and
      PL. SB 216763 administration improved spatial memory whereas lithium treatment
      had no effect. Analysis of neuronal local field potentials in anesthetized
      animals revealed that whereas both repeated SB 216763 (2.5 mg/kg) and lithium
      (100 mg/kg) induced a theta frequency spike in HIP at approximately 10 Hz, only
      SB 216763 treatment induced an overall increase in theta power (4-12 Hz) compared
      to vehicle. Acute administration of either drug suppressed slow (32-59 Hz) and
      fast (61-100 Hz) gamma power. In PL, both drugs induced an increase in theta
      power. Repeated SB 216763 increased HIP-PL coherence across all frequencies
      except delta, whereas lithium selectively suppressed delta coherence. These
      findings demonstrate that GSK-3 plays a direct role in the regulation of theta
      oscillations in regions critically involved in cognition, and highlight a
      potential mechanism by which GSK-3 may contribute to cognitive decline in
      disorders of cognitive dysfunction.

PMID- 29375365
TI  - Declines in Connected Language Are Associated with Very Early Mild Cognitive
      Impairment: Results from the Wisconsin Registry for Alzheimer's Prevention.
AB  - Changes to everyday spoken language ("connected language") are evident in persons
      with AD dementia, yet little is known about when these changes are first
      detectable on the continuum of cognitive decline. The aim of this study was to
      determine if participants with very early, subclinical memory declines were also
      showing declines in connected language. We analyzed connected language samples
      obtained from a simple picture description task at two time points in 264
      participants from the Wisconsin Registry for Alzheimer's Prevention (WRAP). In
      parallel, participants were classified as either "Cognitively Healthy" or "Early
      Mild Cognitive Impairment" based on longitudinal neuropsychological test
      performance. Linear mixed effects models were used to analyze language parameters
      that were extracted from the connected language samples using automated feature
      extraction. Participants with eMCI status declined faster in features of speech
      fluency and semantic content than those who were cognitively stable. Measures of
      lexical diversity and grammatical complexity were not associated with eMCI status
      in this group. These findings provide novel insights about the relationship
      between cognitive decline and everyday language, using a quick, inexpensive, and
      performance-based method.

PMID- 29375367
TI  - Commentary: Comparison of the Long-Term Effect of Positioning the Cathode in tDCS
      in Tinnitus Patients.

PMID- 29375366
TI  - Sex Hormones and Healthy Psychological Aging in Women.
AB  - Besides their key role in reproduction, estrogens have effects in several organs
      in the body, as confirmed by the identification of estrogen receptors (ER) in
      multiple tissues. Experimental evidence has shown that estrogens have significant
      impacts on the central nervous system (CNS), and a key question is to what extent
      the fall in estrogen levels in the blood that occurs with increasing age,
      particularly around and following the menopause, has an impact on the cognitive
      function and psychological health of women, specifically regarding mood. This
      review will consider direct effects of menopausal changes in estrogens on the
      brain, including cognitive function and mood. Secondary pathways whereby health
      factors affected by changes in estrogens may interact with CNS functions, such as
      cardiovascular factors, will be reviewed as well insofar as they also have an
      impact on cognitive function. Finally, because decline in estrogens may induce
      changes in the CNS, there is interest in clarifying whether hormone therapy may
      offer a beneficial balance and the impact of hormone therapy on cognition will
      also be considered.

PMID- 29375368
TI  - The Correlation between Early Stages of Life Exposed to Chinese Famine and
      Cognitive Decline in Adulthood: Nutrition of Adulthood Plays an Important Role in
      the Link?
AB  - Objective: The aim of this study was to investigate whether people exposed to the
      Chinese Famine in fetal period or in multiple stages of childhood are associated
      with cognitive decline in adulthood. Furthermore, the nutritional environment of
      adulthood was explored as an important factor in this correlation. Methods: 1162
      adults born between 1952 and 1964 were recruited. They were divided into five
      groups which were non-exposed group, fetal-exposed group, early childhood-exposed
      group, mid childhood-exposed group and late childhood-exposed group. Cognitive
      function was measured by using a comprehensive neuropsychological battery test,
      including Montreal cognitive assessment-Beijing version, mini-mental state
      examination, auditory verbal learning test, digit span forward, digit span
      backward, trail making test, and digit symbol test. Semi-quantified food
      frequency questionnaire (FFQ) was used to assess the dietary nutrition in their
      adulthood. The dietary nutrient consumption pattern was identified by Two-step
      and K-means cluster analysis. Results: The significant differences in cognitive
      function were manifested in different groups. Compared with non-exposed group,
      subjects in fetal-exposed group had a higher risk of mild cognitive impairment
      (MCI) (OR 1.51 95% CI 1.02-2.23, P = 0.039) and global cognitive decline (OR 1.68
      59% CI 1.02-2.77, P = 0.044). The similar result was also observed in subjects of
      early childhood-exposed group. Otherwise, subjects who were classified in high
      nutrient consumption pattern had higher risk of cognitive decline. Moreover, the
      higher consumption of several nutrients such as fat, carbohydrate and manganese
      were associated with worse performance on digit span forward, digit span
      backward, trail making test A, trail making test B and digit symbol. Conclusion:
      Early stages of life exposed to the Chinese Famine were associated with higher
      risk of cognitive decline in adulthood. The stronger associations were manifested
      in the people with high nutrient consumption pattern. The consumption of fat,
      carbohydrate and manganese were associated with multiple domains cognitive
      decline.

PMID- 29375369
TI  - Innovations in Doctoral Training and Research on Tinnitus: The European School on
      Interdisciplinary Tinnitus Research (ESIT) Perspective.
AB  - Tinnitus is a common medical condition which interfaces many different
      disciplines, yet it is not a priority for any individual discipline. A change in
      its scientific understanding and clinical management requires a shift toward
      multidisciplinary cooperation, not only in research but also in training. The
      European School for Interdisciplinary Tinnitus research (ESIT) brings together a
      unique multidisciplinary consortium of clinical practitioners, academic
      researchers, commercial partners, patient organizations, and public health
      experts to conduct innovative research and train the next generation of tinnitus
      researchers. ESIT supports fundamental science and clinical research projects in
      order to: (1) advancing new treatment solutions for tinnitus, (2) improving
      existing treatment paradigms, (3) developing innovative research methods, (4)
      performing genetic studies on, (5) collecting epidemiological data to create new
      knowledge about prevalence and risk factors, (6) establishing a pan-European data
      resource. All research projects involve inter-sectoral partnerships through
      practical training, quite unlike anything that can be offered by any single
      university alone. Likewise, the postgraduate training curriculum fosters a deep
      knowledge about tinnitus whilst nurturing transferable competencies in personal
      qualities and approaches needed to be an effective researcher, knowledge of the
      standards, requirements and professionalism to do research, and skills to work
      with others and to ensure the wider impact of research. ESIT is the seed for
      future generations of creative, entrepreneurial, and innovative researchers,
      trained to master the upcoming challenges in the tinnitus field, to implement
      sustained changes in prevention and clinical management of tinnitus, and to shape
      doctoral education in tinnitus for the future.

PMID- 29375371
TI  - Commentary: Combating Sale of Counterfeit and Falsified Medicines Online: A
      Losing Battle.

PMID- 29375370
TI  - The Evaluation of Geroprotective Effects of Selected Flavonoids in Drosophila
      melanogaster and Caenorhabditis elegans.
AB  - Flavonoids is an intensively studied group of natural compounds with antioxidant,
      antineoplastic, antihyperglycemic, cardioprotective, and neuroprotective
      properties. The present study intends to investigate the geroprotective action of
      three selected flavonoids (naringin, luteolin, chrysin) in two model organisms,
      Caenorhabditis elegans and Drosophila melanogaster. Luteolin and chrysin were
      shown to improve lifespan parameters when administered to both model organisms.
      The observed positive effects of these flavonoids in D. melanogaster were limited
      to females and were not associated with reduced fecundity or locomotor
      impairment. The life-extending effects of flavonoids were observed in N2 wild
      type worms but absent in aak-2(gt33) mutants implying that these effects can be
      associated with AMP-activated protein kinase activity. Naringin improved lifespan
      parameters of C. elegans, but had no effect on D. melanogaster females; in some
      cases, naringin was found to decrease the lifespan of males. Compared to chrysin
      and luteolin, however, naringin more effectively activates Nrf2 target genes
      (particularly, GstD1) under oxidative stress. Then we compared molecular
      mechanisms of studied compounds and a well-known geroprotector rapamycin, using
      software tool GeroScope. There are no transcriptomic data on luteolin or chrysin
      provided by LINCS Project database. The bioinformatics comparison of
      transcriptomics data for A549 and MCF7 human cell lines treated with rapamycin or
      naringin revealed that these compounds share just a few common signaling pathways
      and quite distinct in their geroprotective action. Thus, based on C. elegans
      effects of naringin, luteolin, chrysin on lifespan we have revealed new potential
      geroprotectors.

PMID- 29375372
TI  - Computational Model of Antidepressant Response Heterogeneity as Multi-pathway
      Neuroadaptation.
AB  - Current hypotheses cannot fully explain the clinically observed heterogeneity in
      antidepressant response. The therapeutic latency of antidepressants suggests that
      therapeutic outcomes are achieved not by the acute effects of the drugs, but
      rather by the homeostatic changes that occur as the brain adapts to their chronic
      administration. We present a computational model that represents the known
      interactions between the monoaminergic neurotransmitter-producing brain regions
      and associated non-monoaminergic neurotransmitter systems, and use the model to
      explore the possible ways in which the brain can homeostatically adjust to
      chronic antidepressant administration. The model also represents the neuron
      specific neurotransmitter receptors that are known to adjust their strengths
      (expressions or sensitivities) in response to chronic antidepressant
      administration, and neuroadaptation in the model occurs through sequential
      adjustments in these receptor strengths. The main result is that the model can
      reach similar levels of adaptation to chronic administration of the same
      antidepressant drug or combination along many different pathways, arriving
      correspondingly at many different receptor strength configurations, but not all
      of those adapted configurations are also associated with therapeutic elevations
      in monoamine levels. When expressed as the percentage of adapted configurations
      that are also associated with elevations in one or more of the monoamines, our
      modeling results largely agree with the percentage efficacy rates of
      antidepressants and antidepressant combinations observed in clinical trials. Our
      neuroadaptation model provides an explanation for the clinical reports of
      heterogeneous outcomes among patients chronically administered the same
      antidepressant drug regimen.

PMID- 29375374
TI  - Traditional Herbal Medicine-Derived Sulforaphene LFS-01 Reverses Colitis in Mice
      by Selectively Altering the Gut Microbiota and Promoting Intestinal Gamma-Delta T
      Cells.
AB  - Sulforaphene (LFS-01) is a natural compound derived from traditional herbal
      medicine. Here, we show that oral administration of LFS-01 is able to
      dramatically alter the skewed gut microbiota and reverse colitis in model mice
      associated with an increase of intestinal gammadeltaT cells. Through 16S rDNA
      sequencing, we showed that LFS-01 can selectively suppress enteric pathogens such
      as Escherichia-Shigella and Helicobacter whereas the protective strains including
      Lactobacillus and Lachnospiraceae were significantly expanded after LFS-01
      treatment. Interestingly, we demonstrated that LFS-01 administration can
      significantly promote the IL-17+gammadeltaT cells in model mice in response to
      the expanded Lactobacillus. We verified that the intracellular components of
      Lactobacillus can stimulate the growth of IL-17+gammadeltaT cells upon
      preincubation. The increased IL-17A after LFS-01 treatment in turn recovers the
      disrupted occludin subcellular location and protects the epithelial barrier in
      the colon of model mice. Remarkably, LFS-01 does not show apparent toxicity to
      animals and we demonstrated that LFS-01 also exerts strong protective effects in
      TNBS-induced colitis rats. Therefore, LFS-01 holds great promise for the
      treatment of inflammatory bowel disease (IBD) and warrants translation for use in
      clinical trials. Our work provided a new avenue for the treatment of IBD based on
      the strategy of harnessing intestinal symbiosis.

PMID- 29375373
TI  - Pathophysiological Role of Purines and Pyrimidines in Neurodevelopment: Unveiling
      New Pharmacological Approaches to Congenital Brain Diseases.
AB  - In recent years, a substantial body of evidence has emerged demonstrating that
      purine and pyrimidine synthesis and metabolism play major roles in controlling
      embryonic and fetal development and organogenesis. Dynamic and time-dependent
      changes in the expression of purine metabolizing enzymes (such as
      ectonucleotidases and adenosine deaminase) represent a key checkpoint for the
      correct sequential generation of the different signaling molecules, that in turn
      activate their specific membrane receptors. In neurodevelopment, Ca2+ release
      from radial glia mediated by P2Y1 purinergic receptors is fundamental to allow
      neuroblast migration along radial glia processes, and their correct positioning
      in the different layers of the developing neocortex. Moreover, ATP is involved in
      the development of synaptic transmission and contributes to the establishment of
      functional neuronal networks in the developing brain. Additionally, several
      purinergic receptors (spanning from adenosine to P2X and P2Y receptor subtypes)
      are differentially expressed by neural stem cells, depending on their maturation
      stage, and their activation tightly regulates cell proliferation and
      differentiation to either neurons or glial cells, as well as their correct
      colonization of the developing telencephalon. The purinergic control of
      neurodevelopment is not limited to prenatal life, but is maintained in postnatal
      life, when it plays fundamental roles in controlling oligodendrocyte maturation
      from precursors and their terminal differentiation to fully myelinating cells.
      Based on the above-mentioned and other literature evidence, it is now
      increasingly clear that any defect altering the tight regulation of purinergic
      transmission and of purine and pyrimidine metabolism during pre- and post-natal
      brain development may translate into functional deficits, which could be at the
      basis of severe pathologies characterized by mental retardation or other
      disturbances. This can occur either at the level of the recruitment and/or
      signaling of specific nucleotide or nucleoside receptors or through genetic
      alterations in key steps of the purine salvage pathway. In this review, we have
      provided a critical analysis of what is currently known on the pathophysiological
      role of purines and pyrimidines during brain development with the aim of
      unveiling new future strategies for pharmacological intervention in different
      neurodevelopmental disorders.

PMID- 29375375
TI  - Single- and Multiple-Dose Trials to Determine the Pharmacokinetics, Safety,
      Tolerability, and Sex Effect of Oral Ginsenoside Compound K in Healthy Chinese
      Volunteers.
AB  - Background and objectives: Ginsenoside compound K (CK) is a candidate drug for
      rheumatoid arthritis therapy. The objective of this study was to investigate the
      pharmacokinetic properties, safety and tolerability of CK. Methods: In
      randomized, double-blind trials, 76 healthy Chinese subjects received 1 of 7
      single oral doses (25, 50, 100, 200, 400, 600, 800 mg) of CK or placebo under
      fasting condition, and another 36 subjects received repeated oral doses (100,
      200, or 400 mg) of CK or placebo for up to 9 days a week after a corresponding
      single dose, after breakfast. Both sexes were equally represented in the two
      trials. Pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol
      (PPD) were calculated and statistically analyzed according to the plasma
      concentration data. Tolerability was evaluated by adverse events (AEs) and
      laboratory examinations. Results: The range of time to maximum concentration
      (Tmax) was 1.5-6.0 h, with a linear increase in the exposure of CK over the dose
      range of 100-400 mg. Steady state was reached after the 7th administration, and
      the accumulation index range was 2.60-2.78. Sex differences were characterized by
      a higher exposure in females than males with the single administration after
      breakfast. In addition, no severe AEs were observed. Conclusion: CK was safe and
      well-tolerated over the treatment period. The sex- and food-related impacts on CK
      pharmacokinetics need further investigations to be validated. (Registration
      number: ChiCTR-TRC-14004824 and ChiCTR-IPR-15006107,
      http://www.chictr.org.cn/index.aspx).

PMID- 29375376
TI  - Omeprazole Inhibits Cell Proliferation and Induces G0/G1 Cell Cycle Arrest
      through Up-regulating miR-203a-3p Expression in Barrett's Esophagus Cells.
AB  - Existing data suggest that proton pump inhibitors (PPIs), particularly
      omeprazole, have significant anti-tumor action in monotherapy and or combination
      chemotherapy. Hedgehog (Hh) signaling pathway represents a leading candidate as a
      molecular mediator of Barrett's esophagus (BE). Studies have indicated reduced
      miRNAs in BE progression, however, little is known about the latent anti-neoplasm
      effects of miRNAs in BE cells. Here, we investigated whether omeprazole could
      inhibit BE progression by regulating Hh pathway and explored the promising Hh
      targeted miRNAs in BE cells. We conducted qRT-PCR and immunoblotting assay to
      evaluate the effects of omeprazole on the expression of Hh signaling components
      and miR-203a-3p in CP-A and CP-B cells. The promising target genes of miR-203a-3p
      were predicted by bioinformatics methods, and verified by luciferase assays and
      qRT-PCR. The effects of omeprazole on BE cell proliferation and cell cycle
      distribution were determined. The overexpression or silencing of miR-203a-3p was
      performed to test its anti-proliferative effects. Finally, rescue experiments
      that miR-203a-3p inhibitor alleviated the effects of omeprazole on decreasing the
      levels of Gli1 mRNA, protein and luciferase were performed. Mechanistic studies
      showed that omeprazole could inhibit the expression of Gli1 and the nuclear
      localization of Gli1. Moreover, we determined that omeprazole could selectively
      up-regulated the expression of miR-203a-3p, and Gli1 was a bona fide target of
      miR-203a-3p. miR-203a-3p inhibitor alleviated the suppressing effects of
      omeprazole on Gli1 luciferase activity, mRNA and protein level. The functional
      assay suggested that omeprazole could dose-dependently inhibit BE cell growth and
      induce cell cycle arrest in G0/G1 phase. Additionally, overexpression and
      silencing of miR-203a-3p in BE cells disrupted cell cycle progress, resulting in
      suppressing and accelerating cell proliferation, respectively. Taken together,
      these data provide a novel mechanism of potentially anti-neoplastic effects for
      omeprazole through modulation of miR-203a-3p expression and thus suppressing
      Hh/Gli1 signaling in BE cells.

PMID- 29375377
TI  - Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances
      Mesothelioma Cell Death from Chemotherapy.
AB  - Reactive oxygen species (ROS) can promote or inhibit tumorigenesis. In
      mesothelioma, asbestos exposure to serous membranes induces ROS through iron
      content and chronic inflammation, and ROS promote cell survival signaling in
      mesothelioma. Moreover, a current chemotherapy regimen for mesothelioma
      consisting of a platinum and antifolate agent combination also induce ROS.
      Mesothelioma is notoriously chemotherapy-resistant, and we propose that ROS
      induced by cisplatin and pemetrexed may promote cell survival signaling pathways,
      which ultimately may contribute to chemotherapy resistance. In The Cancer Genome
      Atlas datasets, we found AXL kinase expression is relatively high in mesothelioma
      compared to other cancer samples. We showed that ROS induce the phosphorylation
      of AXL, which was blocked by the selective inhibitor BGB324 in VMC40 and P31
      mesothelioma cells. We also showed that cisplatin and pemetrexed induce the
      phosphorylation of AXL and Akt, which was also blocked by BGB324 as well as by N
      acetylcysteine antioxidant. AXL knockdown in these cells enhances sensitivity to
      cisplatin and pemetrexed. Similarly, AXL inhibitor BGB324 also enhances
      sensitivity to cisplatin and pemetrexed. Finally, higher synergy was observed
      when cells were pretreated with BGB324 before adding chemotherapy. These results
      demonstrate cisplatin and pemetrexed induce ROS that activate AXL, and blocking
      AXL activation enhances the efficacy of cisplatin and pemetrexed. These results
      suggest AXL inhibition combined with the current chemotherapy regimen may
      represent an effective strategy to enhance the efficacy of chemotherapy in
      mesothelioma. This is the first study, to our knowledge, on chemotherapy-induced
      activation of AXL and cell survival pathways associated with ROS signaling.

PMID- 29375378
TI  - Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with
      Early Recurrence in Hepatocellular Carcinoma.
AB  - The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the
      reasons for the poor rate of survival is the high rate of recurrence caused by
      intrahepatic metastas is that adversely affects long-term outcome. Many studies
      have indicated that microRNAs play an important role in HCC, but there has been
      no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In
      the present study, we found that miR-483-5p was significantly upregulated in RHCC
      tissues of short-term recurrence (<= 2 years) by miRNA microarray screening, and
      can significantly promote migration and invasion of HCC cells in vitro and
      increase intrahepatic metastasis in nude mice in vivo. Furthermore, we
      demonstrated that activated leukocyte cell adhesion molecule (ALCAM), which
      significantly suppressed migration and invasion of HCC cells, was a direct target
      of miR-483-5p, and the re-introduction of ALCAM expression could antagonize the
      promoting effects of miR-483-5p on the capacity of HCC cells for migration and
      invasion. In addition, expression level of ALCAM was negatively correlated with
      microvascular invasion and tumor size recognized as prognostic factors. The cases
      which were negative for ALCAM expression had shorter time to recurrence than
      positive cases, and univariate and multivariate survival analyses showed that
      ALCAM was an independent risk factor of HCC recurrence. qRT-PCR and Western
      blotting showed that the expression of EMT related genes (MMP-2, MMP-9, E-caherin
      and vimentin) significantly changed as a result of interfering or overexpression
      of ALCAM, and ALCAM was significantly associated with EMT in HCC. These results
      suggest that the miR-483-5p/ALCAM axis is an important regulator in invasion and
      metastasis and biomarker for recurrence risk assessment of HCC.

PMID- 29375379
TI  - Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects
      Mice against Bacterial Sepsis.
AB  - The NLRP3 inflammasome plays a critical role in mediating the innate immune
      defense against pathogenic infections, but aberrant activation of NLRP3
      inflammasome has been linked to a variety of inflammatory diseases. Thus
      targeting the NLRP3 inflammasome represents a promising therapeutic for the
      treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron
      breviscapus (Vant.) Hand.-Mazz. and has been reported to exhibit potent anti
      inflammatory activities, but the underlying mechanism is only partly understood.
      In this study, we aimed to investigate whether scutellarin could affect the
      activation of NLRP3 inflammasome in macrophages. The results showed that
      scutellarin dose-dependently reduced caspase-1 activation and decreased mature
      interleukin-1beta (IL-1beta) release in lipopolysaccharide (LPS)-primed
      macrophages upon ATP or nigericin stimulation, indicating that scutellarin
      inhibited NLRP3 inflammasome activation in macrophages. Consistent with this,
      scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages
      treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and
      its oligomerization were blocked by scutellarin pre-treatment. Intriguingly,
      scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed
      macrophages, which was completely blocked by selective PKA inhibitor H89,
      suggesting that PKA signaling had been involved in the action of scutellarin to
      suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of
      scutellarin on NLRP3 inflammasome activation was completely counteracted by H89
      or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1beta has
      a critical role in sepsis, the in vivo activity of scutellarin was assayed in a
      mouse model of bacterial sepsis, which was established by intraperitoneally
      injection of a lethal dose of viable Escherichia coli. Oral administration of
      scutellarin significantly improved the survival of mice with bacterial sepsis. In
      line with this, scutellarin treatment significantly reduced serum IL-1beta levels
      and attenuated the infiltration of inflammatory cells in the liver of E. coli
      infected mice. These data indicated that scutellarin suppressed NLRP3
      inflammasome activation in macrophages by augmenting PKA signaling, highlighting
      its potential therapeutic application for treating NLRP3-related inflammatory
      diseases.

PMID- 29375380
TI  - Steroidal Pyrimidines and Dihydrotriazines as Novel Classes of Anticancer Agents
      against Hormone-Dependent Breast Cancer Cells.
AB  - Most breast and prostate tumors are hormone-dependent, making it possible to use
      hormone therapy in patients with these tumors. The design of effective endocrine
      drugs that block the growth of tumors and have no severe side effects is a
      challenge. Thereupon, synthetic steroids are promising therapeutic drugs for the
      treatment of diseases such as hormone-dependent breast and prostate cancers.
      Here, we describe novel series of steroidal pyrimidines and dihydrotriazines with
      anticancer activities. A flexible approach to unknown pyrimidine and
      dihydrotriazine derivatives of steroids with selective control of the
      heterocyclization pattern is disclosed. A number of 18-nor-5alpha-androsta-2,13
      diene[3,2-d]pyrimidine, androsta-2-ene[3,2-d]pyrimidine, Delta1, 3, 5(10)
      estratrieno[16,17-d]pyrimidine, and 17-chloro-16-dihydrotriazine steroids were
      synthesized by condensations of amidines with beta-chlorovinyl aldehydes derived
      from natural hormones. The synthesized compounds were screened for cytotoxicity
      against breast cancer cells and showed IC50 values of 7.4 MUM and higher.
      Compounds were tested against prostate cancer cells and exhibited
      antiproliferative activity with IC50 values of 9.4 MUM and higher comparable to
      that of cisplatin. Lead compound 4a displayed selectivity in ERalpha-positive
      breast cancer cells. At 10 MUM concentration, this heterosteroid inhibited 50% of
      the E2-mediated ERalpha activity and led to partial ERalpha down-regulation. The
      ERalpha reporter assay and immunoblotting were supported by the docking study,
      which showed the probable binding mode of compound 4a to the estrogen receptor
      pocket. Thus, heterosteroid 4a proved to be a selective ERalpha modulator with
      the highest antiproliferative activity against hormone-dependent breast cancer
      and can be considered as a candidate for further anticancer drug development. In
      total, the synthesized heterosteroids may be considered as new promising classes
      of active anticancer agents.

PMID- 29375381
TI  - MicroRNA-145 Increases the Apoptosis of Activated Hepatic Stellate Cells Induced
      by TRAIL through NF-kappaB Signaling Pathway.
AB  - During the liver fibrosis recovery stage tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) can effectively induce apoptosis of activated hepatic
      stellate cells (HSCs). Normal hepatic stellate cells are resistant to TRAIL
      cytotoxicity. Therefore, enhancing the sensitivity of TRAIL-induced apoptosis of
      HSCs may be useful to treat hepatic fibrogenesis. Here, we demonstrated that miR
      145 and TRAIL were down-regulated in both liver fibrosis tissue samples and
      transforming growth factor-beta1 induced HSCs, concomitant with increased the
      expression of ZEB2. In addition, we found that mimics-mediated over-expression of
      miR-145 led to resistance to the ZEB2 expression and up-regulation of the TRAIL
      induced apoptosis after treatment of LX-2 cells with TRAIL. Furthermore, ZEB2
      siRNA transfected LX-2 cells showed the increased sensitivity to TRAIL-induced
      apoptosis. Whereas, opposite results were obtained in miR-145-inhibitor group or
      ZEB2 plasmid group. Moreover, miR-145 regulated ZEB2 gene expression by
      specifically interacting with the 3'-UTR of ZEB2 mRNA to inhibit the expression
      of ZEB2. Further studies showed that the over-expression of ZEB2 could inhibit
      TRAIL-induced apoptosis via inhibiting nuclear factor-kappaB (NF-kappaB)
      signaling pathway in LX-2 cells. Collectively, our data suggest that up
      regulation of miR-145 can down-regulate ZEB2 expression, consequently promoting
      TRAIL-induced apoptosis in LX-2 cells through NF-kappaB signaling pathway, which
      facilitates the resolution of liver fibrosis.

PMID- 29375382
TI  - Bergenin, Acting as an Agonist of PPARgamma, Ameliorates Experimental Colitis in
      Mice through Improving Expression of SIRT1, and Therefore Inhibiting NF-kappaB
      Mediated Macrophage Activation.
AB  - Bergenin, isolated from the herb of Saxifraga stolonifera Curt. (Hu-Er-Cao), has
      anti-inflammatory, antitussive and wound healing activities. The aim of the
      present study was to identify the effect of bergenin on experimental colitis, and
      explored the related mechanisms. Our results showed that oral administration of
      bergenin remarkably alleviated disease symptoms of mice with dextran sulfate
      sodium (DSS)-induced colitis, evidenced by reduced DAI scores, shortening of
      colon length, MPO activity and pathologic abnormalities in colons. Bergenin
      obviously inhibited the mRNA and protein expressions of IL-6 and TNF-alpha in
      colon tissues, but not that of mucosal barrier-associated proteins occludin, E
      cadherin and MUC-2. In vitro, bergenin significantly inhibited the expressions of
      IL-6 and TNF-alpha as well as nuclear translocation and DNA binding activity of
      NF-kappaB-p65 in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and
      RAW264.7 cells, which was almost reversed by addition of PPARgamma antagonist
      GW9662 and siPPARgamma. Subsequently, bergenin was identified as a PPARgamma
      agonist. It could enter into macrophages, bind with PPARgamma, promote nuclear
      translocation and transcriptional activity of PPARgamma, and increase mRNA
      expressions of CD36, LPL and ap2. In addition, bergenin significantly up
      regulated expression of SIRT1, inhibited acetylation of NF-kappaB-p65 and
      increased association NF-kappaB-p65 and IkappaBalpha. Finally, the correlation
      between activation of PPARgamma and attenuation of colitis, inhibition of IL-6
      and TNF-alpha expressions, NF-kappaB-p65 acetylation and nuclear translocation,
      and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS
      induced colitis and/or LPS-stimulated macrophages. In summary, bergenin could
      ameliorate colitis in mice through inhibiting the activation of macrophages via
      regulating PPARgamma/SIRT1/NF-kappaB-p65 pathway. The findings can provide
      evidence for the further development of bergenin as an anti-UC drug, and offer a
      paradigm for the recognization of anti-UC mechanisms of compound with similar
      structure occurring in traditional Chinese medicines.

PMID- 29375383
TI  - Human UDP-Glucuronosyltransferase 2B4 and 2B7 Are Responsible for Naftopidil
      Glucuronidation in Vitro.
AB  - Naftopidil (NAF) is widely used for the treatment of benign prostatic hyperplasia
      and prevention of prostate cancer in elderly men. These patients receive a
      combination of drugs, which involves high risk for drug-drug interaction. NAF
      exhibits superior efficacy but must be administered at a much higher dosage than
      other therapeutic drugs. We previously showed that extensive glucuronidation of
      NAF enantiomers caused poor bioavailability. However, the metabolic pathway and
      mechanism of action of NAF enantiomer remain to be elucidated. The present study
      was performed to identify the human UDP-glucuronosyltransferases (UGTs)
      responsible for the glucuronidation of NAF enantiomers and to investigate the
      potential inhibition of UGT activity by NAF. The major metabolic sites examined
      were liver and kidney, which were compared with intestine. Screening of 12
      recombinant UGTs showed that UGT2B7 primarily contributed to the metabolism of
      both enantiomers. Moreover, enzyme kinetics for R(+)-NAF, UGT2B7 (mean Km, 21
      MUM; mean Vmax, 1043 pmol/min/mg) showed significantly higher activity than
      observed for UGT2B4 and UGT1A9. UGT2B4 (mean Km, 55 MUM; mean Vmax, 1976
      pmol/min/mg) and UGT2B7 (mean Km, 38 MUM; mean Vmax, 1331 pmol/min/mg) showed
      significantly higher catalysis of glucuronidation of S(-)-NAF than UGT1A9. In
      human liver microsomes, R(+)-NAF and S(-)-NAF also inhibited UGT1A9: mean Ki
      values for R(+)-NAF and S(-)-NAF were 10.0 MUM and 11.5 MUM, respectively. These
      data indicate that UGT2B7 was the principal enzyme mediating glucuronidation of
      R(+)-NAF and S(-)-NAF. UGT2B4 plays the key role in the stereoselective
      metabolism of NAF enantiomers. R(+)-NAF and S(-)-NAF may inhibit UGT1A9.
      Understanding the metabolism of NAF enantiomers, especially their interactions
      with metabolic enzymes, will help to elucidate potential drug-drug interactions
      and to optimize the administration of this medicine.

PMID- 29375385
TI  - Adenine Nucleotides Attenuate Murine T Cell Activation Induced by Concanavalin A
      or T Cell Receptor Stimulation.
AB  - Extracellular ATP and its metabolites affect various cellular immune responses,
      including T cell function, but there are apparently conflicting reports
      concerning the effects of adenine nucleotides on T cells. For example, it has
      been reported that ATP-mediated activation of P2 receptor is involved in T cell
      activation; activation of adenosine receptors suppresses T cell function; and 1
      mM ATP induces T cell death via activation of P2X7 receptor. Therefore, in this
      work we investigated in detail the effects of 100-250 MUM ATP, ADP, or AMP on
      murine T cell activation. First, an in vitro study showed that pretreatment of
      murine splenic T cells with 100-250 MUM ATP, ADP, or AMP significantly suppressed
      the concanavalin A (ConA)-induced release of cytokines, including IL-2. This
      suppression was not due to induction of cell death via the P2X7 receptor or to an
      immunosuppressive effect of adenosine. ATP attenuated the expression of CD25, and
      decreased the cell proliferation ability of activated T cells. The release of IL
      2 by ConA-stimulated lymphocytes was suppressed by post-treatment with ATP, as
      well as by pretreatment. These results suggest that exogenous ATP suppresses the
      activation of T cells. Secondly, we evaluated the effect of ATP in a ConA-treated
      mice. Treatment with ATP attenuated the increase of IL-2 concentration in the
      blood. Overall, these results suggest that adenine nucleotides might have
      potential as supplemental therapeutic agents for T cell-mediated immune diseases,
      by suppressing T cell activation.

PMID- 29375384
TI  - The Role of Adenosine Receptors in Psychostimulant Addiction.
AB  - Adenosine receptors (AR) are a family of G-protein coupled receptors, comprised
      of four members, named A1, A2A, A2B, and A3 receptors, found widely distributed
      in almost all human body tissues and organs. To date, they are known to
      participate in a large variety of physiopathological responses, which include
      vasodilation, pain, and inflammation. In particular, in the central nervous
      system (CNS), adenosine acts as a neuromodulator, exerting different functions
      depending on the type of AR and consequent cellular signaling involved. In terms
      of molecular pathways and second messengers involved, A1 and A3 receptors inhibit
      adenylyl cyclase (AC), through Gi/o proteins, while A2A and A2B receptors
      stimulate it through Gs proteins. In the CNS, A1 receptors are widely distributed
      in the cortex, hippocampus, and cerebellum, A2A receptors are localized mainly in
      the striatum and olfactory bulb, while A2B and A3 receptors are found at low
      levels of expression. In addition, AR are able to form heteromers, both among
      themselves (e.g., A1/A2A), as well as with other subtypes (e.g., A2A/D2), opening
      a whole range of possibilities in the field of the pharmacology of AR. Nowadays,
      we know that adenosine, by acting on adenosine A1 and A2A receptors, is known to
      antagonistically modulate dopaminergic neurotransmission and therefore reward
      systems, being A1 receptors colocalized in heteromeric complexes with D1
      receptors, and A2A receptors with D2 receptors. This review documents the present
      state of knowledge of the contribution of AR, particularly A1 and A2A, to
      psychostimulants-mediated effects, including locomotor activity, discrimination,
      seeking and reward, and discuss their therapeutic relevance to psychostimulant
      addiction. Studies presented in this review reinforce the potential of A1
      agonists as an effective strategy to counteract psychostimulant-induced effects.
      Furthermore, different experimental data support the hypothesis that A2A/D2
      heterodimers are partly responsible for the psychomotor and reinforcing effects
      of psychostimulant drugs, such as cocaine and amphetamine, and the stimulation of
      A2A receptor is proposed as a potential therapeutic target for the treatment of
      drug addiction. The overall analysis of presented data provide evidence that
      excitatory modulation of A1 and A2A receptors constitute promising tools to
      counteract psychostimulants addiction.

PMID- 29375386
TI  - The Case for TAAR1 as a Modulator of Central Nervous System Function.
AB  - TAAR1 is widely expressed across the mammalian brain, particularly in limbic and
      monoaminergic areas, allegedly involved in mood, attention, memory, fear, and
      addiction. However, the subcellular distribution of TAAR1 is still unclear, since
      TAAR1 signal is largely intracellular. In vitro, TAAR1 is activated with
      nanomolar to micromolar affinity by some endogenous amines, particularly p
      tyramine, beta-phenylethylamine, and 3-iodothyronamine (T1AM), the latter
      representing a novel branch of thyroid hormone signaling. In addition, TAAR1
      responds to a number of psychoactive drugs, i.e., amphetamines, ergoline
      derivatives, bromocriptine and lisuride. Trace amines have been identified as
      neurotransmitters in invertebrates, and they are considered as potential
      neuromodulators. In particular, beta-phenylethylamine and p-tyramine have been
      reported to modify the release and/or the response to dopamine, norepinephrine,
      acetylcholine and GABA, while evidence of cross-talk between TAAR1 and other
      aminergic receptors has been provided. Systemic or intracerebroventricular
      injection of exogenous T1AM produced prolearning and antiamnestic effects,
      reduced pain threshold, decreased non-REM sleep, and modulated the firing rate of
      adrenergic neurons in locus coeruleus. However each of these substances may have
      additional molecular targets, and it is unclear whether their endogenous levels
      are sufficient to produce significant TAAR1 activation in vivo. TAAR1 knock out
      mice show a worse performance in anxiety and working memory tests, and they are
      more prone to develop ethanol addiction. They also show increased locomotor
      response to amphetamine, and decreased stereotypical responses induced by
      apomorphine. Notably, human genes for TAARs cluster on chromosome 6 at q23,
      within a region whose mutations have been reported to confer susceptibility to
      schizophrenia and bipolar disorder. For human TAAR1, around 200 non-synonymous
      and 400 synonymous single nucleotide polymorphisms have been identified, but
      their functional consequences have not been extensively investigated yet. In
      conclusion, the bulk of evidence points to a significant physiological role of
      TAAR1 in the modulation of central nervous system function and a potential
      pharmacological role of TAAR1 agonists in neurology and/or psychiatry. However,
      the specific effects of TAAR1 stimulation are still controversial, and many
      crucial issues require further investigation.

PMID- 29375387
TI  - The Role of Ferroptosis in Cancer Development and Treatment Response.
AB  - Ferroptosis is a process driven by accumulated iron-dependent lipid ROS that
      leads to cell death, which is a distinct regulated cell death comparing to other
      cell death. The lethal metabolic imbalance resulted from GSH depletion or
      inactivation of glutathione peroxidase 4 is the executor of ferroptosis within
      the cancer cell. Small molecules-induced ferroptosis has a strong inhibition of
      tumor growth and enhances the sensitivity of chemotherapeutic drugs, especially
      in the condition of drug resistance. These evidences have highlighted the
      importance of ferroptosis in cancer therapeutics, but the roles of ferroptosis in
      tumorigenesis and development remain unclear. This article provides an overview
      of the mechanisms of ferroptosis, highlights the role of ferroptosis in cancer
      and discusses strategies for therapeutic modulation.

PMID- 29375389
TI  - No Change in Bicarbonate Transport but Tight-Junction Formation Is Delayed by
      Fluoride in a Novel Ameloblast Model.
AB  - We have recently developed a novel in vitro model using HAT-7 rat ameloblast
      cells to functionally study epithelial ion transport during amelogenesis. Our
      present aims were to identify key transporters of bicarbonate in HAT-7 cells and
      also to examine the effects of fluoride exposure on vectorial bicarbonate
      transport, cell viability, and the development of transepithelial resistance. To
      obtain monolayers, the HAT-7 cells were cultured on Transwell permeable filters.
      We monitored transepithelial resistance (TER) as an indicator of tight junction
      formation and polarization. We evaluated intracellular pH changes by
      microfluorometry using the fluorescent indicator BCECF. Activities of ion
      transporters were tested by withdrawal of various ions from the bathing medium,
      by using transporter specific inhibitors, and by activation of transporters with
      forskolin and ATP. Cell survival was estimated by alamarBlue assay. Changes in
      gene expression were monitored by qPCR. We identified the activity of several ion
      transporters, NBCe1, NHE1, NKCC1, and AE2, which are involved in intracellular pH
      regulation and vectorial bicarbonate and chloride transport. Bicarbonate
      secretion by HAT-7 cells was not affected by acute fluoride exposure over a wide
      range of concentrations. However, tight-junction formation was inhibited by 1 mM
      fluoride, a concentration which did not substantially reduce cell viability,
      suggesting an effect of fluoride on paracellular permeability and tight-junction
      formation. Cell viability was only reduced by prolonged exposure to fluoride
      concentrations greater than 1 mM. In conclusion, cultured HAT-7 cells are
      functionally polarized and are able to transport bicarbonate ions from the
      basolateral to the apical fluid spaces. Exposure to 1 mM fluoride has little
      effect on bicarbonate secretion or cell viability but delays tight-junction
      formation, suggesting a novel mechanism that may contribute to dental fluorosis.

PMID- 29375388
TI  - The Potential of Nanotechnology in Medically Assisted Reproduction.
AB  - Reproductive medicine is a field of science which searches for new alternatives
      not only to help couples achieve pregnancy and preserve fertility, but also to
      diagnose and treat diseases which can impair the normal operation of the
      reproductive tract. Assisted reproductive technology (ART) is a set of
      methodologies applied to cases related to infertility. Despite being highly
      practiced worldwide, ART presents some challenges, which still require special
      attention. Nanotechnology, as a tool for reproductive medicine, has been
      considered to help overcome some of those impairments. Over recent years,
      nanotechnology approaches applied to reproductive medicine have provided
      strategies to improve diagnosis and increase specificity and sensitivity. For in
      vitro embryo production, studies in non-human models have been used to deliver
      molecules to gametes and embryos. The exploration of nanotechnology for ART would
      bring great advances. In this way, experiments in non-human models to test the
      development and safety of new protocols using nanomaterials are very important
      for informing potential future employment in humans. This paper presents recent
      developments in nanotechnology regarding impairments still faced by ART: ovary
      stimulation, multiple pregnancy, and genetic disorders. New perspectives for
      further use of nanotechnology in reproductive medicine studies are also
      discussed.

PMID- 29375390
TI  - The Effects of Tai Chi Training in Patients with Heart Failure: A Systematic
      Review and Meta-Analysis.
AB  - Heart Failure (HF) is associated with significantly high morbidity and mortality.
      We performed a meta-analysis and updated new evidences from randomized controlled
      trials (RCTs) to determine the effects of Tai Chi (TC) in patients with HF.
      Electronic literature search of Medline, PubMed, EMBASE, the Cochrane Library,
      China national knowledge infrastructure (CNKI), and Wan Fang Database was
      conducted from inception of their establishment until 2017. And we also searched
      Clinical Trials Registries (https://clinicaltrials.gov/ and www.controlled
      trials.com) for on-going studies. A total of 11 trials with 656 patients were
      available for analysis. The results suggested that TC was associated with an
      obviously improved 6-min walk distance [6MWD, weighted mean difference (WMD)
      65.29 m; 95% CI 32.55-98.04] and quality of life (Qol, WMD -11.52 points; 95% CI 
      16.5 to -6.98) and left ventricular ejection fraction (LVEF, WMD 9.94%; 95% CI
      6.95 to 12.93). TC was shown to reduce serum B-type natriuretic peptide [BNP,
      standard mean difference (SMD) -1.08 pg/mL; 95% CI -1.91 to -0.26] and heart rate
      (HR, WMD -2.52 bpm; 95% CI -3.49 to -1.55). In summary, our meta-analysis
      demonstrated the clinical evidence about TC for HF is inconclusive. TC could
      improve 6MWD, Qol and LVEF in patients with HF and may reduce BNP and HR.
      However, there is a lack of evidence to support TC altering other important long
      term clinical outcomes so far. Further larger and more sustainable RCTs are
      urgently needed to investigate the effects of TC.

PMID- 29375391
TI  - Angiotensin-(1-7) Inhibits Thrombin-Induced Endothelial Phenotypic Changes and
      Reactive Oxygen Species Production via NADPH Oxidase 5 Downregulation.
AB  - Background and Aims: The angiotensin-(1-7)/angiotensin-converting enzyme 2/Mas
      receptor axis counter-regulates the detrimental effects of angiotensin II.
      Beneficial effects of angiotensin-(1-7), including anti-inflammation, oxidative
      stress reduction, and anti-thrombosis, have been reported. Previous studies
      documented that ramipril decreased thrombin generation in human hypertension and
      that the anti-thrombotic effects of captopril and losartan were angiotensin-(1-7)
      dependent, suggesting an interaction between thrombin and angiotensin-(1-7).
      However, it is not clear whether angiotensin-(1-7) can alleviate the endothelial
      phenotypic changes induced by thrombin. We have previously documented
      cytoskeleton remodeling, cell adhesion, and cell migration as dominant altered
      phenotypes in thrombin-stimulated human aortic endothelial cells (HAECs). In this
      study, we investigated whether angiotensin-(1-7) can modulate thrombin-induced
      phenotypic changes. Furthermore, we investigated whether NAPDH oxidase 5 (Nox5)
      produced reactive oxygen species (ROS) play a significant role in angiotensin-(1
      7)-mediated phenotypic changes. Methods: HAECs were pretreated with 100 nM
      angiotensin-(1-7) for 1 h, followed by stimulation with 2 units/mL thrombin for
      different times. Immunofluorescent assay, monocyte adhesion assay, wound-healing
      assay, ROS assay, real-time PCR, Western blotting, and Nox5 siRNA transfection
      were conducted. HAECs were pretreated with the ROS scavenger N-acetylcysteine
      (NAC) to determine whether thrombin-induced phenotypic changes depended on ROS
      production. Results: Angiotensin-(1-7) prevented thrombin-induced actin
      cytoskeleton derangements, monocyte adhesion, and migratory impairment. Nox5
      siRNA transfection confirmed that thrombin-induced Nox5 expression stimulated ROS
      production and increased HO-1/NQO-1/ICAM-1/VCAM-1 gene expression, all of which
      were decreased by angiotensin-(1-7). Phenotypic changes induced by thrombin were
      prevented by NAC pretreatment. Conclusion: Angiotensin-(1-7) prevents actin
      cytoskeleton derangement, monocyte adhesion, and migration impairment induced by
      thrombin via downregulation of ROS production. In addition, thrombin-induced Nox5
      expression is involved in the production of ROS, and angiotensin-(1-7) decreases
      ROS through its inhibitory effect on Nox5 expression.

PMID- 29375392
TI  - Effects of Soccer Training on Anthropometry, Body Composition, and Physical
      Fitness during a Soccer Season in Female Elite Young Athletes: A Prospective
      Cohort Study.
AB  - The objectives of this study were to (i) describe soccer training (e.g., volume,
      types), anthropometry, body composition, and physical fitness and (ii) compute
      associations between soccer training data and relative changes of anthropometry,
      body composition, and physical fitness during a soccer season in female elite
      young athletes. Seasonal training (i.e., day-to-day training volume/types) as
      well as variations in anthropometry (e.g., body height/mass), body composition
      (e.g., lean body/fat mass), and physical fitness (e.g., muscle strength/power,
      speed, balance) were collected from 17 female elite young soccer players (15.3 +/
      0.5 years) over the training periods (i.e., preparation, competition,
      transition) of a soccer season that resulted in the German championship title in
      under-17 female soccer. Training volume/types, anthropometrics, body composition,
      and physical fitness significantly varied over a soccer season. During the two
      preparation periods, higher volumes in resistance and endurance training were
      performed (2.00 <= d <= 18.15; p < 0.05), while higher sprint and tactical
      training volumes were applied during the two competition periods (2.22 <= d <=
      11.18; p < 0.05). Body height and lean body mass increased over the season (2.50
      <= d <= 3.39; p < 0.01). In terms of physical fitness, significant performance
      improvements were found over the soccer season in measures of balance, endurance,
      and sport-specific performance (2.52 <= d <= 3.95; p < 0.05). In contrast, no
      statistically significant changes were observed for measures of muscle
      power/endurance, speed, and change-of-direction speed. Of note, variables of
      muscle strength (i.e., leg extensors) significantly decreased (d = 2.39; p <
      0.01) over the entire season. Our period-specific sub-analyses revealed
      significant performance improvements during the first round of the season for
      measures of muscle power/endurance, and balance (0.89 <= d <= 4.01; p < 0.05).
      Moreover, change-of-direction speed significantly declined after the first round
      of the season, i.e., transition period (d = 2.83; p < 0.01). Additionally,
      significant medium-to-large associations were observed between training and
      anthropometrics/body composition/physical fitness (-0.541 <= r <= 0.505). Soccer
      training and/or growth/maturation contributed to significant variations in
      anthropometry, body composition, and physical fitness outcomes throughout the
      different training periods over the course of a soccer season in female elite
      young soccer players. However, changes in components of fitness were inconsistent
      (e.g., power, speed, strength). Thus, training volume and/or types should be
      carefully considered in order to develop power-, speed- or strength-related
      fitness measures more efficiently throughout the soccer season.

PMID- 29375393
TI  - Evaluation of Short and Long Term Cold Stress Challenge of Nerve Grow Factor,
      Brain-Derived Neurotrophic Factor, Osteocalcin and Oxytocin mRNA Expression in
      BAT, Brain, Bone and Reproductive Tissue of Male Mice Using Real-Time PCR and
      Linear Correlation Analysis.
AB  - The correlation between the Ngf/p75ntr-Ntrk1 and Bdnf, Osteocalcin-Ost/Gprc6a and
      Oxytocin-Oxt/Oxtr genes, was challenged investigating their mRNA levels in 3
      months-old mice after cold-stress (CS). Uncoupling protein-1 (Ucp-1) was used as
      positive control. Control mice were maintained at room temperature T = 25 degrees
      C, CS mice were maintained at T = 4 degrees C for 6 h and 5-days (N = 15 mice).
      RT-PCR experiments showed that Ucp-1 and Ngf genes were up-regulated after 6 h CS
      in brown adipose tissues (BAT), respectively, by 2 and 1.5-folds; Ucp-1 was
      upregulated also after 5-days, while Ngfr (p75ntr) and Ntrk1 genes were
      downregulated after 6 h and 5-days CS in BAT. NGF and P75NTR were upregulated in
      bone and testis following 5-days, and P75NTR in testis after 6 h CS. Bdnf was
      instead up-regulated in bone following 5-days CS and down-regulated in testis.
      OST was upregulated by 16 and 3-fold in bone and BAT, respectively, following 5
      days CS. Gprc6a was upregulated after 6 h in brain, while Bglap (Ost) gene was
      downregulated. Oxt gene was upregulated by 5-fold following 5-days CS in bone.
      Oxtr was upregulated by 0.5 and 0.3-fold, respectively, following 6 h and 5-days
      CS in brain. Oxtr and Oxt were downregulated in testis and in BAT. The changes in
      the expression levels of control genes vs. genes following 6 h and 5-days CS were
      correlated in all tissues, but not in BAT. Correlation in BAT was improved
      eliminating Ngfr (p75ntr) data. The correlation in brain was lost eliminating
      Oxtr data. In sum, Ucp-1 potentiation in BAT after cold stress is associated with
      early Ngf-response in the same tissue and trophic action in bone and testis. In
      contrast, BDNF exerts bone and neuroprotective effects. Similarly to Ucp-1, Bglap
      (Ost) signaling is enhanced in bone and BAT while it may exert local
      neuroprotective effects thought its receptor. Ngfr (p75ntr) regulates the
      adaptation to CS through a feed-back loop in BAT. Oxtr regulates the gene
      response to CS through a feed-forward loop in brain. Overall these results expand
      the understanding of the physiology of these molecules under metabolic
      thermogenesis.

PMID- 29375395
TI  - Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological
      Considerations.
AB  - Carbonyl emissions from tobacco cigarettes represent a substantial health risk
      contributing to smoking-related morbidity and mortality. As expected, this is an
      important research topic for tobacco harm reduction products, in an attempt to
      compare the relative risk of these products compared to tobacco cigarettes. In
      this study, a systematic review of the literature available on PubMed was
      performed analyzing the studies evaluating carbonyl emissions from e-cigarettes.
      A total of 32 studies were identified and presented. We identified a large
      diversity of methodologies, with substantial discrepancies in puffing patterns,
      aerosol collection and analytical methods as well as reported units of
      measurements. Such discrepancies make comparisons difficult, and in some cases
      the accuracy of the findings cannot be determined. Importantly, control for the
      generation of dry puffs was not performed in the vast majority of studies,
      particularly in studies using variable power devices, which could result in
      testing conditions and reported carbonyl levels that have no clinical relevance
      or context. Some studies have been replicated, verifying the presence of dry puff
      conditions. Whenever realistic use conditions were ensured, carbonyl emissions
      from e-cigarettes were substantially lower than tobacco cigarette smoke, while
      newer generation (bottom-coil, cotton wick) atomizers appeared to emit minimal
      levels of carbonyls with questionable clinical significance in terms of health
      risk. However, extremely high levels of carbonyl emissions were reported in some
      studies, and all these studies need to be replicated because of potentially
      important health implications.

PMID- 29375394
TI  - Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right
      Ventricular Hypertrophic Failure.
AB  - Pulmonary arterial hypertension (PAH) alters the geometries of both ventricles of
      the heart. While the right ventricle (RV) hypertrophies, the left ventricle (LV)
      atrophies. Multiple lines of clinical and experimental evidence lead us to
      hypothesize that the impaired stroke volume and systolic pressure of the LV are a
      direct consequence of the effect of pressure overload in the RV, and that atrophy
      in the LV plays only a minor role. In this study, we tested this hypothesis by
      examining the mechanoenergetic response of the atrophied LV to RV hypertrophy in
      rats treated with monocrotaline. Experiments were performed across multiple
      scales: the whole-heart in vivo and ex vivo, and its trabeculae in vitro. Under
      the in vivo state where the RV was pressure-overloaded, we measured reduced
      systemic blood pressure and LV ventricular pressure. In contrast, under both ex
      vivo and in vitro conditions, where the effect of RV pressure overload was
      circumvented, we found that LV was capable of developing normal systolic pressure
      and stress. Nevertheless, LV atrophy played a minor role in that LV stroke volume
      remained lower, thereby contributing to lower LV mechanical work output.
      Concomitantly lower oxygen consumption and change of enthalpy were observed, and
      hence LV energy efficiency was unchanged. Our internally consistent findings
      between working-heart and trabecula experiments explain the rapid improvement of
      LV systolic function observed in patients with chronic pulmonary hypertension
      following surgical relief of RV pressure overload.

PMID- 29375396
TI  - Individual-Based Modeling Approach to Assessment of the Impacts of Landscape
      Complexity and Climate on Dispersion, Detectability and Fate of Incipient Medfly
      Populations.
AB  - The objective of the presented study was to demonstrate the potential of a bottom
      up "ethological" approach and individual-based model of Markov-like stochastic
      processes, employed to gain insights into the factors driving behavior and fate
      of the invasive propagule, which determine the initial stages of pest invasion
      and "cryptic" existence of the localized, ultra-low density incipient pest
      populations. The applied model, PESTonFARM, is driven by the parameters derived
      directly from the behavior and biology of the target insect species, and
      spatiotemporal traits of the local terrain and climate. The model projections are
      actively generated by behavior of the primary causative actors of the invasion
      processes-individual "virtual" insects-members of the initial propagules or
      incipient populations. Algorithms of the model were adjusted to reflect behavior
      and ecology of the Mediterranean fruit fly, Ceratitis capitata, used as a case
      example in the presented study. The model was parametrized based on compiled
      published experimental information about C. capitata behavior and development,
      and validated using published data from dispersion and trapping studies. The
      model reliably simulated behavior, development and dispersion of individual
      members of an invasive cohort, and allowed to quantify pest establishment and
      detection chances in landscapes of varying spatiotemporal complexity, host
      availability and climates. The results support the common view that, under
      optimal conditions (farmland with continuous fruit availability and suitable
      climate), even a single propagule of medium size (100 females) usually results in
      pest establishment and detection within the first year post-invasion. The results
      demonstrate, however, that under specific sub-optimal conditions determined by
      the local climate, weather fluctuations and landscape topography (e.g., sub
      urban), the incipient cryptic populations may occasionally continue for several
      generations, and remain undetected by typical pest surveillance grids for the
      periods extending beyond 2-years post-invasion.

PMID- 29375397
TI  - The Cerebral Brain-Derived Neurotrophic Factor Pathway, Either Neuronal or
      Endothelial, Is Impaired in Rats with Adjuvant-Induced Arthritis. Connection with
      Endothelial Dysfunction.
AB  - Cognitive abilities are largely dependent on activation of cerebral tropomyosin
      related kinase B receptors (TrkB) by brain-derived neurotrophic factor (BDNF)
      that is secreted under a bioactive form by both neurons and endothelial cells. In
      addition, there is mounting evidence for a link between endothelial function and
      cognition even though the underlying mechanisms are not well known. Therefore, we
      investigated the cerebral BDNF pathway, either neuronal or endothelial, in
      rheumatoid arthritis (RA) that combines both endothelial dysfunction (ED) and
      impaired cognition. Adjuvant-induced arthritis (AIA) in rats was used as a model
      of RA. Clinical inflammatory symptoms were evaluated from an arthritis score and
      brains were collected at day 31 +/- 2 post-immunization. Neuronal expression of
      BDNF and TrkB phosphorylated at tyrosine 816 (p-TrkB) was examined in brain
      slices. Endothelial BDNF and p-TrkB expression was examined on both brain slices
      (hippocampal arterioles) and isolated cerebral microvessels-enriched fractions
      (vessels downstream to arterioles). The connection between endothelial nitric
      oxide (NO) and BDNF production was explored on the cerebrovascular fractions
      using endothelial NO synthase (eNOS) levels as a marker of NO production, Nomega
      Nitro-L-arginine methyl ester hydrochloride (L-NAME) as a NOS inhibitor and
      glyceryl-trinitrate as a slow releasing NO donor. Brain slices displayed lower
      BDNF and p-TrkB staining in both neurons and arteriolar endothelial cells in AIA
      than in control rats. For endothelial cells but not neurons, a strong correlation
      was observed between BDNF and p-TrkB staining. Of note, a strong correlation was
      also observed between neuronal p-TrkB and endothelial BDNF staining. In cerebral
      microvessels-enriched fractions, AIA led to decreased BDNF and eNOS levels with a
      positive association between the 2 parameters. These effects coincided with
      decreased BDNF and p-TrkB staining in endothelial cells. The exposure of AIA
      cerebrovascular fractions to GTN increased BDNF levels while the exposure of
      control fractions to L-NAME decreased BDNF levels. Changes in the cerebral BDNF
      pathway were not associated with arthritis score. The present study reveals that
      AIA impairs the endothelial and neuronal BDNF/TrkB pathway, irrespective of the
      severity of inflammatory symptoms but dependent on endothelial NO production.
      These results open new perspectives for the understanding of the link between ED
      and impaired cognition.

PMID- 29375398
TI  - Dynamic Changes in Chemosensory Gene Expression during the Dendrolimus punctatus
      Mating Process.
AB  - The insect chemosensory system is pivotal for interactions with their
      environments, and moths have especially sensitive olfaction. Exploration of the
      connection between the plasticity of olfactory-guided and molecular level
      pathways in insects is important for understanding the olfactory recognition
      mechanisms of insects. The pine caterpillar moth, Dendrolimus punctatus Walker,
      is a dominant conifer defoliator in China, and mating is the priority for adults
      of this species, during which sex pheromone recognition and oviposition site
      location are the main activities; these activities are all closely related to
      chemosensory genes. Thus, we aimed to identify chemosensory related genes and
      monitor the spectrum of their dynamic expression during the entire mating process
      in D. punctatus. In this study, we generated transcriptome data from male and
      female adult D. punctatus specimens at four mating stages: eclosion, calling,
      copulation, and post-coitum. These data were analyzed using bioinformatics tools
      to identify the major olfactory-related gene families and determine their
      expression patterns during mating. Levels of odorant binding proteins (OBPs),
      chemosensory proteins (CSPs), and odorant receptors (ORs) were closely correlated
      with mating behavior. Comparison with ORs from other Dendrolimus and Lepidoptera
      species led to the discovery of a group of ORs specific to Dendrolimus.
      Furthermore, we identified several genes encoding OBPs and ORs that were
      upregulated after mating in females; these genes may mediate the location of host
      plants for oviposition via plant-emitted volatiles. This work will facilitate
      functional research into D. punctatus chemosensory genes, provide information
      about the relationship between chemosensory genes and important physiological
      activities, and promote research into the mechanisms underlying insect olfactory
      recognition.

PMID- 29375399
TI  - Inflammatory and Oxidative Responses Induced by Exposure to Commonly Used e
      Cigarette Flavoring Chemicals and Flavored e-Liquids without Nicotine.
AB  - Background: The respiratory health effects of inhalation exposure to e-cigarette
      flavoring chemicals are not well understood. We focused our study on the immuno
      toxicological and the oxidative stress effects by these e-cigarette flavoring
      chemicals on two types of human monocytic cell lines, Mono Mac 6 (MM6) and U937.
      The potential to cause oxidative stress by these flavoring chemicals was assessed
      by measuring the production of reactive oxygen species (ROS). We hypothesized
      that the flavoring chemicals used in e-juices/e-liquids induce an inflammatory
      response, cellular toxicity, and ROS production. Methods: Two monocytic cell
      types, MM6 and U937 were exposed to commonly used e-cigarette flavoring
      chemicals; diacetyl, cinnamaldehyde, acetoin, pentanedione, o-vanillin, maltol
      and coumarin at different doses between 10 and 1,000 MUM. Cell viability and the
      concentrations of the secreted inflammatory cytokine interleukin 8 (IL-8) were
      measured in the conditioned media. Cell-free ROS produced by these commonly used
      flavoring chemicals were also measured using a 2',7'dichlorofluorescein diacetate
      probe. These DCF fluorescence data were expressed as hydrogen peroxide (H2O2)
      equivalents. Cytotoxicity due to the exposure to selected e-liquids was assessed
      by cell viability and the IL-8 inflammatory cytokine response in the conditioned
      media. Results: Treatment of the cells with flavoring chemicals and flavored e
      liquid without nicotine caused cytotoxicity dose-dependently. The exposed
      monocytic cells secreted interleukin 8 (IL-8) chemokine in a dose-dependent
      manner compared to the unexposed cell groups depicting a biologically significant
      inflammatory response. The measurement of cell-free ROS by the flavoring
      chemicals and e-liquids showed significantly increased levels of H2O2 equivalents
      in a dose-dependent manner compared to the control reagents. Mixing a variety of
      flavors resulted in greater cytotoxicity and cell-free ROS levels compared to the
      treatments with individual flavors, suggesting that mixing of multiple flavors of
      e-liquids are more harmful to the users. Conclusions: Our data suggest that the
      flavorings used in e-juices can trigger an inflammatory response in monocytes,
      mediated by ROS production, providing insights into potential pulmonary toxicity
      and tissue damage in e-cigarette users.

PMID- 29375400
TI  - Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in
      Drosophila Glial Cells.
AB  - Circadian clocks consist of molecular negative feedback loops that coordinate
      physiological, neurological, and behavioral variables into "circa" 24-h rhythms.
      Rhythms in behavioral and other circadian outputs tend to weaken during aging, as
      evident in progressive disruptions of sleep-wake cycles in aging organisms.
      However, less is known about the molecular changes in the expression of clock
      genes and proteins that may lead to the weakening of circadian outputs. Western
      blot studies have demonstrated that the expression of the core clock protein
      PERIOD (PER) declines in the heads of aged Drosophila melanogaster flies. This
      age-related decline in PER does not occur in the central pacemaker neurons but
      has been demonstrated so far in retinal photoreceptors. Besides photoreceptors,
      clock proteins are also expressed in fly glia, which play important roles in
      neuronal homeostasis and are further categorized into subtypes based on
      morphology and function. While previous studies of mammalian glial cells have
      demonstrated the presence of functional clocks in astrocytes and microglia, it is
      not known which glial cell types in Drosophila express clock proteins and how
      their expression may change in aged individuals. Here, we conducted
      immunocytochemistry experiments to identify which glial subtypes express PER
      protein suggestive of functional circadian clocks. Glial cell subtypes that
      showed night-time accumulation and day-time absence in PER consistent with
      oscillations reported in the pacemaker neurons were selected to compare the level
      of PER protein between young and old flies. Our data demonstrate that some glial
      subtypes show rhythmic PER expression and the relative PER levels become dampened
      with advanced age. Identification of glial cell types that display age-related
      dampening of PER levels may help to understand the cellular changes that
      contribute to the loss of homeostasis in the aging brain.

PMID- 29375402
TI  - Mood Instability Is a Precursor of Relationship and Marital Difficulties: Results
      from Prospective Data from the British Health and Lifestyle Surveys.
AB  - The DSM system implies that affective instability is caused by reactivity to
      interpersonal events. We used the British Health and Lifestyle Survey that
      surveyed community residents in 1984 and again in 1991 to study competing
      hypotheses: that mood instability (MI) leads to interpersonal difficulties or
      vice versa. We analyzed data from 5,352 persons who participated in both waves of
      the survey. Factor analysis of the Eysenck Personality Inventory neuroticism
      scale was used to derive a 4-item scale for MI. We used depression measures that
      were previously derived by factor analyzing the General Health Questionnaire. We
      tested the competing hypotheses by regressing variables at follow-up against
      baseline variables. The results showed that MI in 1984 clearly predicted the
      development of interpersonal problems in 1991. After adjusting for depression,
      depression becomes the main predictor of spousal difficulties, but MI remains a
      predictor of interpersonal difficulties with family and friends. Attempts to
      investigate the reverse hypothesis were ambiguous. The clinical implication is
      that when MI and interpersonal problems are reported, the MI should be treated
      first, or at least concurrently.

PMID- 29375401
TI  - Neurological Soft Signs in Schizophrenia: An Update on the State- versus Trait
      Perspective.
AB  - Background: Neurological soft signs (NSS) represent minor neurological signs,
      which indicate non-specific cerebral dysfunction. In schizophrenia, their
      presence has been documented extensively across all stages of the disease. Until
      recently, NSS were considered an endophenotype or a trait phenomenon. During the
      past years, however, researchers report fluctuations of the NSS scores. Aims: To
      further clarify the question whether NSS exhibit state or trait components or
      both, studies that have investigated NSS longitudinally were reviewed. Method:
      Studies which have assessed NSS longitudinally in adults suffering from
      schizophrenia, were searched for. The time frame was January 1966 to June 2017.
      Studies on teenagers were excluded because of interferences between brain
      maturation and pathology. Results: Twenty-nine follow-up studies were identified.
      They included patients during different stages of their illness and mainly used
      established instruments for NSS assessment. Patients with a first episode or a
      remitting course predominantly show a decrease of NSS over time, whereas a
      worsening of NSS can be found in the chronically ill. It was shown that change of
      NSS total scores over time is predominantly caused by motor system subscales and
      to a lesser extent by sensory integration scales. With respect to medication, the
      majority of studies agree on a relationship between medication response and
      improvement of NSS while the type of antipsychotic does not seem to play a major
      role. Moreover, where information on side-effects is given, it does not favor a
      strong relationship with NSS. However, NSS seem to correlate with negative and
      cognitive symptoms. Conclusion: Studies manifest a conformity regarding the
      presence of NSS in schizophrenia patients on the one hand. On the other hand,
      fluctuations of NSS scores have been widely described in subgroups. Taken
      together results strongly support a state-trait dichotomy of NSS. Thus, the usage
      of NSS as an endophenotype has to be called into question.

PMID- 29375403
TI  - Stress and Disease Onset in Antineutrophil Cytoplasmic Antibody-Associated
      Vasculitis.
AB  - Objective: To explore the potential contribution of stress as a trigger for
      disease onset in patients with antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis (AAV). Methods: 53 AAV and 85 rheumatoid arthritis (RA)
      patients as well as 53 healthy controls (HC) were thoroughly asked for the number
      and impact of stressful life events, coping strategies, and available social
      support 12 months prior to disease onset. Anxiety, depression, personality
      dimensions, insomnia, and fatigue were also determined. Results: AAV patients
      reported higher scoring of the impact of stressful life events compared to the RA
      and HC group prior to disease onset (2.8 +/- 3.1 vs 1.8 +/- 2.1 vs 1.7 +/- 2.3, p
      values: 0.047 and 0.053, respectively). While the number of reported stressful
      events was found to be significantly higher in AAV vs RA patients but not HC,
      certain coping strategies and social support features were more commonly
      implemented by AAV patients compared to HC, but not RA patients. As far as
      personality and other psychosocial characteristics, AAV patients displayed
      significantly higher psychoticism traits compared to RA, with no other
      differences being detected between AAV patients and both RA and HC. After
      adjusting for potential cofounders, scoring of the impact of stressful life
      events >3 was independently associated with AAV development compared to both RA
      and HC [ORs (95% CI): 4.6 (1.6-13.4) and 4.4 (1.0-19.0), respectively].
      Conclusion: The perceived impact of stressful life events prior to disease onset
      emerged as a contributing factor for AAV development.

PMID- 29375405
TI  - Assessing Social Cognition of Persons with Schizophrenia in a Chinese Population:
      A Pilot Study.
AB  - Social cognition is a core limiting factor of functional recovery among persons
      with schizophrenia. However, there is a lack of standardized and culturally
      relevant assessment tools for evaluating social cognitive performance in Chinese
      persons with schizophrenia. The purposes of this study were to (1) develop and
      validate two social cognitive instruments, the Chinese Facial Emotion
      Identification Test (C-FEIT) and the Chinese Social Cognition and Screening
      Questionnaire (C-SCSQ), that assess three key domains of social cognition and (2)
      to evaluate preliminary psychometric properties of the two assessments. The
      results demonstrated that the C-FEIT and the social cognitive subscales of C-SCSQ
      possess satisfactory content-related validity and test-retest reliability (ICC
      ranging from 0.76 to 0.85). Subscales of the C-FEIT and the C-SCSQ showed low to
      medium correlation with two concurrent neurocognitive measures (absolute values
      of r ranging from 0.22 to 0.45) and concurrent measures of functional performance
      (absolute values of r ranging from 0.22 to 0.46). Our findings generally support
      the use of the C-FEIT and the C-SCSQ as reliable and valid tools for assessing
      emotion perception, theory of mind (intention-inferencing), and hostile
      attributional style, which are the key outcome indicators of social cognitive
      interventions for persons with schizophrenia.

PMID- 29375404
TI  - Default Mode Network Aberrant Connectivity Associated with Neurological Soft
      Signs in Schizophrenia Patients and Unaffected Relatives.
AB  - Brain connectivity and neurological soft signs (NSS) are reportedly abnormal in
      schizophrenia and unaffected relatives, suggesting they might be useful
      neurobiological markers of the illness. NSS are discrete sensorimotor impairments
      thought to correspond to deviant brain development. Although NSS support the
      hypothesis that schizophrenia involves disruption in functional circuits
      involving several hetero modal association areas, little is known about the
      relationship between NSS and brain connectivity. We explored functional
      connectivity abnormalities of the default mode network (DMN) related to NSS in
      schizophrenia. A cross-sectional study was performed with 27 patients diagnosed
      with schizophrenia, 23 unaffected relatives who were unrelated to the
      schizophrenia subjects included in the study, and 35 healthy controls. Subjects
      underwent magnetic resonance imaging scans including a functional resting-state
      acquisition and NSS evaluation. Seed-to-voxel and independent component analyses
      were used to study brain connectivity. NSS scores were significantly different
      between groups, ranging from a higher to lower scores for patients, unaffected
      relatives, and healthy controls, respectively (analysis of variance effect of
      group F = 56.51, p < 0.001). The connectivity analysis revealed significant
      hyperconnectivity in the fusiform gyrus, insular and dorsolateral prefrontal
      cortices, inferior and middle frontal gyri, middle and superior temporal gyri,
      and posterior cingulate cortex [minimum p-family wise error (FWE) < 0.05 for all
      clusters] in patients with schizophrenia as compared with in controls. Also,
      unaffected relatives showed hyperconnectivity in relation to controls in the
      supramarginal association and dorsal posterior cingulate cortices (p-FWE < 0.05
      for all clusters) in patients with schizophrenia as compared with in controls.
      Also, unaffected relatives showed hyperconnectivity in relation to controls in
      the supramarginal association and dorsal posterior cingulate cortices (p-FWE =
      0.001) and in the anterior prefrontal cortex (42 voxels, p-FWE = 0.047). A
      negative correlation was found between left caudate connectivity and NSS [p-FWE =
      0.044, cluster size (k) = 110 voxels]. These findings support the theory of
      widespread abnormal connectivity in schizophrenia, reinforcing DMN
      hyperconnectivity and NSS as neurobiological markers of schizophrenia. The
      results also indicate the caudate nucleus as the gateway to the motor
      consequences of abnormal DMN connectivity.

PMID- 29375406
TI  - DNA Methylation at the DAT Promoter and Risk for Psychopathology:
      Intergenerational Transmission between School-Age Youths and Their Parents in a
      Community Sample.
AB  - Background: The effect of gene polymorphisms and promoter methylation, associated
      with maladaptive developmental outcomes, vary depending on environmental factors
      (e.g., parental psychopathology). Most studies have focused on 0- to 5-year-old
      children, adolescents, or adults, whereas there is dearth of research on school
      age youths and pre-adolescents. Methods: In a sample of 21 families recruited at
      schools, we addressed parents' psychopathological symptoms (through SCL-90-R);
      offspring emotional-behavioral functioning (through CBCL-6-18); dopamine
      transporter gene (DAT1) for epigenetic status of the 5'-untranslated region (UTR)
      and for genotype, i.e., variable number of tandem repeats polymorphism at the 3'
      UTR. Possible associations were explored between bio-genetic and psychological
      characteristics within the same individual and between triplets of children,
      mothers, and fathers. Results: DAT methylation of CpG at positions M1, M6, and M7
      in mothers was correlated with maternal (phobic) anxiety, whereas in fathers'
      position M6 was related to paternal depression, anxiety, hostility, psychoticism,
      and higher Global Severity Index (GSI). No significant correlations were found
      between maternal and offspring DAT methylation. Significant correlations were
      found between fathers' methylation at CpG M1 and children's methylation at CpG
      M6. Linear regressions showed that mothers and fathers' GSI predicted children's
      methylation at CpG sites M2, M3, and M6, whereas fathers' GSI predicted
      children's methylation at CpG sites, particularly M1, M2, and M6. Moreover,
      offspring methylation of DAT at CpG M2 predicted somatic complaint, internalizing
      and attention problems; methylation of DAT at CpG M6 predicted withdraw.
      Conclusion: This study may have important clinical implication for the prevention
      and treatment of emotional-behavioral difficulties in children, as it adds to
      previous knowledge about the role of genetic and environmental factors in
      predicting psychopathological symptoms within non-clinical populations.

PMID- 29375407
TI  - Antenatal Training with Music and Maternal Talk Concurrently May Reduce Autistic
      Like Behaviors at around 3 Years of Age.
AB  - Antenatal training through music and maternal talk to the unborn fetus is a topic
      of general interest for parents-to-be in China, but we still lack a comprehensive
      assessment of their effects on the development of autistic-like behaviors during
      early childhood. During 2014-2016, 34,749 parents of children around the age of 3
      years who were enrolled at kindergarten in the Longhua district of Shenzhen
      participated in this study. Self-administered questionnaires regarding
      demographics, antenatal music training, and maternal talk to the fetus during
      pregnancy were completed by the children's primary caregivers. Autistic-like
      behaviors were assessed using the Autism Behavioral Checklist. Tobit regression
      analyses revealed that antenatal music training and maternal talk to the fetus
      was associated with a reduction in autistic-like behaviors in children, with a
      dose-dependent relationship. Furthermore, factorial analysis of covariance
      indicated a significant interaction effect between antenatal music training and
      maternal talk to the fetus on the autistic-like behaviors and found that children
      who often experienced antenatal music training and maternal talk concurrently had
      the lowest risk of autistic-like behaviors, while children who were never exposed
      to maternal talk and only sometimes experienced antenatal music training had the
      highest risk. Our results suggest that antenatal training through both music and
      maternal talk to the unborn fetus might reduce the risk of children's autistic
      like behaviors at around 3 years of age.

PMID- 29375409
TI  - Systematic Observation: Relevance of This Approach in Preschool Executive
      Function Assessment and Association with Later Academic Skills.
AB  - Executive functions (EFs) are high-level cognitive processes that allow us to
      coordinate our actions, thoughts, and emotions, enabling us to perform complex
      tasks. An increasing number of studies have highlighted the role of EFs in
      building a solid foundation for subsequent development and learning and shown
      that EFs are associated with good adjustment and academic skills. The main
      objective of this study was to analyze whether EF levels in 44 Spanish children
      in the last year of preschool were associated with levels of literacy and math
      skills the following year, that is, in the first year of compulsory education. We
      used a multi-method design, which consisted of systematic observation to observe
      preschool children during play and selective methodology to assess their reading,
      writing, and math skills in the first year of compulsory primary education.
      General linear modeling was used to estimate the percentage of variability in
      academic skills in the first year of primary school that was explained by
      preschool EF abilities. The results showed that preschool EF level, together with
      participants and the instrument used to assess academic skills, explained 99% of
      the variance of subsequent academic performance. Another objective was to
      determine whether our findings were generalizable to the reference population. To
      make this determination, we estimated the optimal sample size for assessing
      preschool EFs. To do this, we performed a generalizability analysis. The
      resulting generalizability coefficient showed that our sample of 44 students was
      sufficient for assessing preschool EFs. Therefore, our results are generalizable
      to the reference population. Our results are consistent with previous reports
      that preschool EF abilities may be associated with subsequent literacy and math
      skills. Early assessment of EFs may therefore contribute to identifying children
      who are likely to experience later learning difficulties and guide the design of
      suitable interventions for the optimization of EFs.

PMID- 29375408
TI  - Mephedrone (4-Methylmethcathinone): Acute Behavioral Effects, Hyperthermic, and
      Pharmacokinetic Profile in Rats.
AB  - Mephedrone (MEPH) is a synthetic cathinone derivative with effects that mimic
      MDMA and/or cocaine. Our study in male Wistar rats provides detailed
      investigations of MEPH's and its primary metabolite nor-mephedrone's (nor-MEPH)
      pharmacokinetics and bio-distribution to four different substrates (serum, brain,
      lungs, and liver), as well as comparative analysis of their effects on locomotion
      [open field test (OFT)] and sensorimotor gating [prepulse inhibition of acoustic
      startle reaction (PPI ASR)]. Furthermore, in order to mimic the crowded condition
      where MEPH is typically taken (e.g., clubs), the acute effect of MEPH on
      thermoregulation in singly- and group-housed rats was evaluated. Pharmacokinetics
      of MEPH and nor-MEPH after MEPH (5 mg/kg, sc.) were analyzed over 8 h using
      liquid chromatography with mass spectrometry. MEPH (2.5, 5, or 20 mg/kg, sc.) and
      nor-MEPH (5 mg/kg, sc.) were administered 5 or 40 min before the behavioral
      testing in the OFT and PPI ASR; locomotion and its spatial distribution, ASR,
      habituation and PPI itself were quantified. The effect of MEPH on rectal
      temperature was measured after 5 and 20 mg/kg, sc. Both MEPH and nor-MEPH were
      detected in all substrates, with the highest levels detected in lungs. Mean
      brain: serum ratios were 1:1.19 (MEPH) and 1:1.91 (nor-MEPH), maximum
      concentrations were observed at 30 min; at 2 and 4 h after administration, nor
      MEPH concentrations were higher compared to the parent drug. While neither of the
      drugs disrupted PPI, both increased locomotion and affected its spatial
      distribution. The effects of MEPH were dose dependent, rapid, and short-lasting,
      and the intensity of locomotor stimulant effects was comparable between MEPH and
      nor-MEPH. Despite the disappearance of behavioral effects within 40 min after
      administration, MEPH induced rectal temperature elevations that persisted for 3 h
      even in singly housed rats. To conclude, we observed a robust, short-lasting, and
      most likely synergistic stimulatory effect of both drugs which corresponded to
      brain pharmacokinetics. The dissociation between the duration of behavioral and
      hyperthermic effects is indicative of the possible contribution of nor-MEPH or
      other biologically active metabolites. This temporal dissociation may be related
      to the risk of prolonged somatic toxicity when stimulatory effects are no longer
      present.

PMID- 29375410
TI  - Math Anxiety Is Related to Some, but Not All, Experiences with Math.
AB  - Math anxiety has been defined as unpleasant feelings of tension and anxiety that
      hinder the ability to deal with numbers and math in a variety of situations.
      Although many studies have looked at situational and demographic factors
      associated with math anxiety, little research has looked at the self-reported
      experiences with math that are associated with math anxiety. The present study
      used a mixed-methods design and surveyed 131 undergraduate students about their
      experiences with math through elementary school, junior high, and high school,
      while also assessing math anxiety, general anxiety, and test anxiety. Some
      reported experiences (e.g., support in high school, giving students plenty of
      examples) were significantly related to the level of math anxiety, even after
      controlling for general and test anxiety, but many other factors originally
      thought to be related to math anxiety did not demonstrate a relation in this
      study. Overall, this study addresses a gap in the literature and provides some
      suggestive specifics of the kinds of past experiences that are related to math
      anxiety and those that are not.

PMID- 29375411
TI  - Electrocortical N400 Effects of Semantic Satiation.
AB  - Semantic satiation is characterised by the subjective and temporary loss of
      meaning after high repetition of a prime word. To study the nature of this
      effect, previous electroencephalography (EEG) research recorded the N400, an ERP
      component that is sensitive to violations of semantic context. The N400 is
      characterised by a relative negativity to words that are unrelated vs. related to
      the semantic context. The semantic satiation hypothesis predicts that the N400
      should decrease with high repetition. However, previous findings have been
      inconsistent. Because of these inconsistent findings and the shortcomings of
      previous research, we used a modified design that minimises confounding effects
      from non-semantic processes. We recorded 64-channel EEG and analysed the N400 in
      a semantic priming task in which the primes were repeated 3 or 30 times.
      Critically, we separated low and high repetition trials and excluded response
      trials. Further, we varied the physical features (letter case and format) of
      consecutive primes to minimise confounding effects from perceptual habituation.
      For centrofrontal electrodes, the N400 was reduced after 30 repetitions (vs. 3
      repetitions). Explorative source reconstructions suggested that activity
      decreased after 30 repetitions in bilateral inferior temporal gyrus, the right
      posterior section of the superior and middle temporal gyrus, right supramarginal
      gyrus, bilateral lateral occipital cortex, and bilateral lateral orbitofrontal
      cortex. These areas overlap broadly with those typically involved in the N400,
      namely middle temporal gyrus and inferior frontal gyrus. The results support the
      semantic rather than the perceptual nature of the satiation effect.

PMID- 29375412
TI  - The Neural Basis of Social Influence in a Dictator Decision.
AB  - Humans tend to reduce inequitable distributions. Previous neuroimaging studies
      have shown that inequitable decisions are related to brain regions that
      associated with negative emotion and signaling conflict. In the highly complex
      human social environment, our opinions and behaviors can be affected by social
      information. In current study, we used a modified dictator game to investigate
      the effect of social influence on making an equitable decision. We found that the
      choices of participants in present task was influenced by the choices of peers.
      However, participants' decisions were influenced by equitable rather than
      inequitable group choices. fMRI results showed that brain regions that related to
      norm violation and social conflict were related to the inequitable social
      influence. The neural responses in the dorsomedial prefrontal cortex, rostral
      cingulate zone, and insula predicted subsequent conforming behavior in
      individuals. Additionally, psychophysiological interaction analysis revealed that
      the interconnectivity between the dorsal striatum and insula was elevated in
      advantageous inequity influence versus no-social influence conditions. We found
      decreased functional connectivity between the medial prefrontal cortex and
      insula, supplementary motor area, posterior cingulate gyrus and dorsal anterior
      cingulate cortex in the disadvantageous inequity influence versus no-social
      influence conditions. This suggests that a disadvantageous inequity influence may
      decrease the functional connectivity among brain regions that are related to
      reward processes. Thus, the neural mechanisms underlying social influence in an
      equitable decision may be similar to those implicated in social norms and reward
      processing.

PMID- 29375413
TI  - Steps to Ensure a Successful Implementation of Occupational Health and Safety
      Interventions at an Organizational Level.
AB  - There is increasing meta-analytic evidence that addresses the positive impact of
      evidence-based occupational health and safety interventions on employee health
      and well-being. However, such evidence is less clear when interventions are
      approached at an organizational level and are aimed at changing organizational
      policies and processes. Given that occupational health and safety interventions
      are usually tailored to specific organizational contexts, generalizing and
      transferring such interventions to other organizations is a complex endeavor. In
      response, several authors have argued that an evaluation of the implementation
      process is crucial for assessing the intervention's effectiveness and for
      understanding how and why the intervention has been (un)successful. Thus, this
      paper focuses on the implementation process and attempts to move this field
      forward by identifying the main factors that contribute toward ensuring a greater
      success of occupational health and safety interventions conducted at the
      organizational level. In doing so, we propose some steps that can guide a
      successful implementation. These implementation steps are illustrated using
      examples of evidence-based best practices reported in the literature that have
      described and systematically evaluated the implementation process behind their
      interventions during the last decade.

PMID- 29375414
TI  - Infants' Motor Proficiency and Statistical Learning for Actions.
AB  - Prior research has shown that infants learn statistical regularities in action
      sequences better than they learn non-action event sequences. This is consistent
      with current theories claiming that the same mechanism guides action observation
      and action execution. The current eye-tracking study tested the prediction, based
      on these theories, that infants' ability to learn statistical regularities in
      action sequences is modulated by their own motor abilities. Eight- to eleven
      month-old infants observed an action sequence containing two deterministic action
      pairs (i.e., action A always followed by action B) embedded within an otherwise
      random sequence. One pair was performed with a whole-hand grasp. The second pair
      was performed with a pincer grasp, a fine motor skill that emerges around 9
      months of age. Infants were then categorized into groups according to which grasp
      was dominant in their motor repertoire. Predictive looks to correct upcoming
      actions during the deterministic pairs were analyzed to measure whether infants
      learned and anticipated the sequence regularities. Findings indicate that infants
      learned the statistical regularities: across motor groups, they made more correct
      than incorrect predictive fixations to upcoming actions. Overall, learning was
      not significantly modulated by their dominant grasping abilities. However,
      infants with a dominant pincer grasp showed an earlier increase in correct
      predictions for the pincer grasp pair and not the whole-hand grasp. Likewise,
      infants with a dominant whole-hand grasp showed an early increase in correct
      predictions for the pair performed with a whole-hand grasp, and not the pincer
      grasp. Together, these findings suggest that infants' ability to learn action
      sequences is facilitated when the observed action matches their own action
      repertoire. However, findings cannot be explained entirely by motor accounts, as
      infants also learned the actions less congruent with their own abilities.
      Findings are discussed in terms of the interplay between the motor system and
      additional non-motor resources during the acquisition of new motor skills in
      infancy.

PMID- 29375415
TI  - Well-being and Anticipation for Future Positive Events: Evidences from an fMRI
      Study.
AB  - Anticipation for future confers great benefits to human well-being and mental
      health. However, previous work focus on how people's well-being correlate with
      brain activities during perception of emotional stimuli, rather than anticipation
      for the future events. Here, the current study investigated how well-being
      relates to neural circuitry underlying the anticipating process of future desired
      events. Using event-related functional magnetic resonance imaging, 40
      participants were scanned while they were performing an emotion anticipation
      task, in which they were instructed to anticipate the positive or neutral events.
      The results showed that bilateral medial prefrontal cortex (MPFC) were activated
      during anticipation for positive events relative to neutral events, and the
      enhanced brain activation in MPFC was associated with higher level of well-being.
      The findings suggest a neural mechanism by which the anticipation process to
      future desired events correlates to human well-being, which provide a future
      oriented view on the neural sources of well-being.

PMID- 29375416
TI  - Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on
      Aggression: A Resting-State fMRI Study.
AB  - A great many of empirical researches have proved that longtime exposure to
      violent video game can lead to a series of negative effects. Although research
      has focused on the neural basis of the correlation between violent video game and
      aggression, little is known whether the spontaneous brain activity is associated
      with violent video game exposure. To address this question, we measured the
      spontaneous brain activity using resting-state functional magnetic resonance
      imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and
      fractional ALFF (fALFF) to quantify spontaneous brain activity. The results
      showed there is no significant difference in ALFF, or fALFF, between violent
      video game group and the control part, indicating that long time exposure to
      violent video games won't significantly influence spontaneous brain activity,
      especially the core brain regions such as execution control, moral judgment and
      short-term memory. This implies the adverse impact of violent video games is
      exaggerated.

PMID- 29375417
TI  - Backward Dependencies and in-Situ wh-Questions as Test Cases on How to Approach
      Experimental Linguistics Research That Pursues Theoretical Linguistics Questions.
AB  - The empirical study of language is a young field in contemporary linguistics.
      This being the case, and following a natural development process, the field is
      currently at a stage where different research methods and experimental approaches
      are being put into question in terms of their validity. Without pretending to
      provide an answer with respect to the best way to conduct linguistics related
      experimental research, in this article we aim at examining the process that
      researchers follow in the design and implementation of experimental linguistics
      research with a goal to validate specific theoretical linguistic analyses. First,
      we discuss the general challenges that experimental work faces in finding a
      compromise between addressing theoretically relevant questions and being able to
      implement these questions in a specific controlled experimental paradigm. We
      discuss the Granularity Mismatch Problem (Poeppel and Embick, 2005) which
      addresses the challenges that research that is trying to bridge the
      representations and computations of language and their
      psycholinguistic/neurolinguistic evidence faces, and the basic assumptions that
      interdisciplinary research needs to consider due to the different conceptual
      granularity of the objects under study. To illustrate the practical implications
      of the points addressed, we compare two approaches to perform linguistic
      experimental research by reviewing a number of our own studies strongly grounded
      on theoretically informed questions. First, we show how linguistic phenomena
      similar at a conceptual level can be tested within the same language using
      measurement of event-related potentials (ERP) by discussing results from two ERP
      experiments on the processing of long-distance backward dependencies that involve
      coreference and negative polarity items respectively in Dutch. Second, we examine
      how the same linguistic phenomenon can be tested in different languages using
      reading time measures by discussing the outcome of four self-paced reading
      experiments on the processing of in-situ wh-questions in Mandarin Chinese and
      French. Finally, we review the implications that our findings have for the
      specific theoretical linguistics questions that we originally aimed to address.
      We conclude with an overview of the general insights that can be gained from the
      role of structural hierarchy and grammatical constraints in processing and the
      existing limitations on the generalization of results.

PMID- 29375418
TI  - Influences of Product Temperature on Emotional Responses to, and Sensory
      Attributes of, Coffee and Green Tea Beverages.
AB  - Coffee and green tea are popular beverages consumed at both hot and cold
      temperatures. When people consume hot beverages concurrently with other
      activities, they may experience at different temperatures over the period of
      consumption. However, there has been limited research investigating the effects
      of product temperatures on emotional responses and sensory attributes of
      beverages. This study aimed to determine whether emotional responses to, and
      sensory attributes of, brewed coffee and green tea vary as a function of sample
      temperature. Using a check-all-that-apply (CATA) method, 157 participants (79 for
      coffee and 78 for green tea) were asked to evaluate either coffee or green tea
      samples served at cold (5 degrees C), ambient (25 degrees C), and hot (65 degrees
      C) temperatures with respect to emotional responses and sensory attributes. The
      results showed that sample temperature could have significant influences on
      emotional responses to, and sensory attributes of, coffee and green tea samples.
      More specifically, 6 and 18 sensory attributes of coffee and green tea samples,
      respectively, significantly differed with sample temperature. Beverage samples
      evaluated at 65 degrees C were characterized, regardless of activation/arousal
      level, by positive emotional responses terms and favorable sensory attributes.
      While beverages evaluated at 25 degrees C were associated more with negative
      emotional responses with low activation/arousal, those evaluated at 5 degrees C
      were more frequently characterized as having negative emotional responses with
      high activation/arousal. Sensory and emotional drivers of liking for both coffee
      and green tea differed both with sample temperature and gender. While both
      emotional responses and sensory attributes were identified as drivers of liking
      among females, only emotional responses were identified as drivers of liking
      among males. In conclusion, this study provides empirical evidence that both
      emotional responses to, and sensory attributes of, coffee and green tea beverages
      can vary with sample temperatures. To provide a better understanding of product
      characteristics, emotional responses to, and sensory attributes of, coffee or
      green tea beverages should be tested over a wider range of product temperatures.

PMID- 29375419
TI  - Reflective and Non-conscious Responses to Exercise Images.
AB  - Images portraying exercise are commonly used to promote exercise behavior and to
      measure automatic associations of exercise (e.g., via implicit association
      tests). The effectiveness of these promotion efforts and the validity of
      measurement techniques partially rely on the untested assumption that the images
      being used are perceived by the general public as portrayals of exercise that is
      pleasant and motivating. The aim of this study was to investigate how content of
      images impacted people's automatic and reflective evaluations of exercise images.
      Participants (N = 90) completed a response time categorization task (similar to
      the implicit association test) to capture how automatically people perceived each
      image as relevant to Exercise or Not exercise. Participants also self-reported
      their evaluations of the images using visual analog scales with the anchors:
      Exercise/Not exercise, Does not motivate me to exercise/Motivates me to exercise,
      Pleasant/Unpleasant, and Energizing/Deactivating. People tended to more strongly
      automatically associate images with exercise if the images were of an outdoor
      setting, presented sport (as opposed to active labor or gym-based) activities,
      and included young (as opposed to middle-aged) adults. People tended to
      reflectively find images of young adults more motivating and relevant to exercise
      than images of older adults. The content of exercise images is an often
      overlooked source of systematic variability that may impact measurement validity
      and intervention effectiveness.

PMID- 29375420
TI  - Rapid L2 Word Learning through High Constraint Sentence Context: An Event-Related
      Potential Study.
AB  - Previous studies have found quantity of exposure, i.e., frequency of exposure
      (Horst et al., 1998; Webb, 2008; Pellicer-Sanchez and Schmitt, 2010), is
      important for second language (L2) contextual word learning. Besides this factor,
      context constraint and L2 proficiency level have also been found to affect
      contextual word learning (Pulido, 2003; Tekmen and Daloglu, 2006; Elgort et al.,
      2015; Ma et al., 2015). In the present study, we adopted the event-related
      potential (ERP) technique and chose high constraint sentences as reading
      materials to further explore the effects of quantity of exposure and proficiency
      on L2 contextual word learning. Participants were Chinese learners of English
      with different English proficiency levels. For each novel word, there were four
      high constraint sentences with the critical word at the end of the sentence.
      Learners read sentences and made semantic relatedness judgment afterwards, with
      ERPs recorded. Results showed that in the high constraint condition where each
      pseudoword was embedded in four sentences with consistent meaning, N400 amplitude
      upon this pseudoword decreased significantly as learners read the first two
      sentences. High proficiency learners responded faster in the semantic relatedness
      judgment task. These results suggest that in high quality sentence contexts, L2
      learners could rapidly acquire word meaning without multiple exposures, and L2
      proficiency facilitated this learning process.

PMID- 29375421
TI  - The Influence of Personal Well-Being on Learning Achievement in University
      Students Over Time: Mediating or Moderating Effects of Internal and External
      University Engagement.
AB  - The current study examined the relationship between students' personal well-being
      and their learning achievement during university study, and whether such
      relationship would be mediated or moderated by university engagement. A total of
      434 university students from one public university in Hong Kong participated in
      the study. The participants completed an online survey consisting of personal
      well-being (cognitive behavioral competence and general positive youth
      development), university engagement, and learning achievement measures (personal
      growth, and accumulated GPA as academic achievement) at four time points with a 1
      year interval. Results showed that personal well-being measured at the beginning
      of university study positively predicted students' personal growth and academic
      achievement after 3 years' study. While the internal dimensions of university
      engagement (academic challenge and learning with peers) showed longitudinal
      significant mediational effect, the external dimensions (experience with faculty
      and campus environment) did not have significant longitudinal moderating effect.
      Nevertheless, external dimensions of student engagement also showed direct effect
      on personal growth and academic achievement. The long-standing positive effects
      of personal well-being on university engagement and subsequently, learning
      achievement during university years call for more attention to the promotion of
      holistic development among university students in Hong Kong.

PMID- 29375422
TI  - Etiological Beliefs, Treatments, Stigmatizing Attitudes toward Schizophrenia.
      What Do Italians and Israelis Think?
AB  - Background: Although scientific research on the etiology of mental disorders has
      improved the knowledge of biogenetic and psychosocial aspects related to the
      onset of mental illness, stigmatizing attitudes and behaviors are still very
      prevalent and pose a significant social problem. Aim: The aim of this study was
      to deepen the knowledge of how attitudes toward people with mental illness are
      affected by specific personal beliefs and characteristics, such as culture and
      religion of the perceiver. More precisely, the main purpose is the definition of
      a structure of variables, namely perceived dangerousness, social closeness, and
      avoidance of the ill person, together with the beliefs about the best treatment
      to be undertaken and the sick person' gender, capable of describing the
      complexity of the stigma construct in particular as far as schizophrenia is
      concerned. Method: The study involved 305 university students, 183 from the
      University of Padua, Italy, and 122 from the University of Haifa, Israel. For the
      analyses, a latent class analysis (LCA) approach was chosen to identify a latent
      categorical structure accounting for the covariance between the observed
      variables. Such a latent structure was expected to be moderated by cultural
      background (Italy versus Israel) and religious beliefs, whereas causal beliefs,
      recommended treatment, dangerousness, social closeness, and public avoidance were
      the manifest variables, namely the observed indicators of the latent variable.
      Results: Two sets of results were obtained. First, the relevance of the manifest
      variables as indicators of the hypothesized latent variable was highlighted.
      Second, a two-latent-class categorical dimension represented by prejudicial
      attitudes, causal beliefs, and treatments concerning schizophrenia was found.
      Specifically, the differential effects of the two cultures and the religious
      beliefs on the latent structure and their relations highlighted the relevance of
      the observed variables as indicators of the expected latent variable. Conclusion:
      The present study contributes to the improvement of the understanding of how
      attitudes toward people with mental illness are affected by specific personal
      beliefs and characteristics of the perceiver. The definition of a structure of
      variables capable of describing the complexity of the stigma construct in
      particular as far as schizophrenia is concerned was achieved from a cross
      cultural perspective.

PMID- 29375423
TI  - Effect of Passive Hyperthermia on Working Memory Resources during Simple and
      Complex Cognitive Tasks.
AB  - The aim of this study was to verify the hypothesis that hyperthermia represents a
      cognitive load limiting available resources for executing concurrent cognitive
      tasks. Electroencephalographic activity (EEG: alpha and theta power) was obtained
      in 10 hyperthermic participants in HOT (50 degrees C, 50% RH) conditions and in a
      normothermic state in CON (25 degrees C, 50% RH) conditions in counterbalanced
      order. In each trial, EEG was measured over the frontal lobe prior to task
      engagement (PRE) in each condition and during simple (One Touch Stockings of
      Cambridge, OTS-4) and complex (OTS-6) cognitive tasks. Core (39.5 +/- 0.5 vs.
      36.9 +/- 0.2 degrees C) and mean skin (39.06 +/- 0.3 vs. 31.6 +/- 0.6 degrees C)
      temperatures were significantly higher in HOT than CON (p < 0.005). Theta power
      significantly increased with task demand (p = 0.017, eta2 = 0.36) and was
      significantly higher in HOT than CON (p = 0.041, eta2 = 0.39). The difference
      between HOT and CON was large (eta2 = 0.40) and significant (p = 0.036) PRE,
      large (eta2 = 0.20) but not significant (p = 0.17) during OTS-4, and disappeared
      during OTS-6 (p = 0.87, eta2 = 0.00). Those changes in theta power suggest that
      hyperthermia may act as an additional cognitive load. However, this load
      disappeared during OTS-6 together with an impaired performance, suggesting a
      potential saturation of the available resources.

PMID- 29375424
TI  - Consequences of Team Job Demands: Role Ambiguity Climate, Affective Engagement,
      and Extra-Role Performance.
AB  - In the absence of clearly established procedures in the workplace, employees will
      experience a negative affective state. This situation influences their well-being
      and their intention to behave in ways that benefit the organization beyond their
      job demands. This impact is more relevant on teamwork where members share the
      perception of ambiguity through emotional contagion (role ambiguity climate). In
      the framework of the job demands-resources model, the present study analyzes how
      high levels of role ambiguity climate can have such an effect to reduce employee
      affective engagement. Over time it has been associated with negative results for
      the organization due to a lack of extra-role performance. The sample included 706
      employees from a multinational company, who were divided into 11 work teams. In
      line with the formulated hypotheses, the results confirm the negative influence
      of the role ambiguity climate on extra-role performance, and the mediated effect
      of affective engagement in the relationship between the role ambiguity climate
      and extra-role performance. These findings indicate that the role ambiguity
      climate is related to the adequate or inadequate functioning of employees within
      a work context.

PMID- 29375425
TI  - Quality of Maternal Parenting of 9-Month-Old Infants Predicts Executive Function
      Performance at 2 and 3 Years of Age.
AB  - Whereas the effects of maternal parenting quality during infants' 2nd year on
      later executive function (EF) have been studied extensively, less is known about
      the impact of maternal parenting quality during the 1st year. The aim of this
      study was to examine whether maternal parenting during infants' 1st year
      predicted EF performance at 2 and 3 years of age in a Chinese sample. Data were
      collected from 96 mother-infant dyads (42 males) when the infants were 6, 9, 25,
      and 38 months old. Cognitive development as a control variable was measured with
      the Bayley Scales of Infant Development II at 6 months. At 9 months, three
      aspects of maternal parenting quality (sensitivity, mind-mindedness, and
      encouragement of autonomy) were assessed with MBQS, mind-mindedness coding
      system, and encouragement of autonomy coding schema within a 15-min mother-infant
      interaction. Three aspects of EF (working memory, inhibitory control, and delay
      EF) were measured at 25 and 38 months with age-appropriate tasks. Hierarchical
      regression analysis showed that maternal mind-mindedness had a more important
      effect than did the encouragement of autonomy and maternal sensitivity during
      infants' preverbal period. More precisely, maternal mind-mindedness at 9 months
      predicted inhibitory control at 2 and 3 years, and maternal encouragement of
      autonomy predicted performance on delay EF tasks at 3 years, maternal sensitivity
      had no observed effect on children's EF. This study suggests that maternal
      parenting quality during the 1st year (maternal mind-mindedness and encouragement
      of autonomy, but not maternal sensitivity) impacts later EF development.

PMID- 29375426
TI  - Affordances and Landscapes: Overcoming the Nature-Culture Dichotomy through Niche
      Construction Theory.
AB  - In this paper we reject the nature-culture dichotomy by means of the idea of
      affordance or possibility for action, which has important implications for
      landscape theory. Our hypothesis is that, just as the idea of affordance can
      serve to overcome the subjective-objective dichotomy, the ideas of landscape and
      ecological niche, properly defined, would allow us to also transcend the nature
      culture dichotomy. First, we introduce an overview of landscape theory,
      emphasizing processual landscape theory as the most suitable approach for
      satisfying both cultural and naturalist approaches. After that, we introduce the
      idea of affordance and we analyze a tension between sociocultural and
      transcultural affordances (affordances that depend on cultural conventions and
      affordances that depend on lawful information and bodily aspects of agents). This
      tension has various implications for landscape theory and ecological niches. Our
      proposal is that sociocultural and transcultural aspects of affordances could be
      systematically accommodated if we apply niche construction theory (the theory
      that explains the process by which organisms modify their selective environments)
      as a methodological framework for explaining the emergence of ecological niches.
      This approach will lead us to an integrative account of landscapes as the
      products of the interaction between human and environmental elements, making it a
      clear example of a concept that transcends the nature-culture dichotomy.

PMID- 29375427
TI  - Measuring the Psychological Distance between an Organization and Its Members-The
      Construction and Validation of a New Scale.
AB  - There exists a lack of specific research methods to estimate the relationship
      between an organization and its employees, which has long challenged research in
      the field of organizational management. Therefore, this article introduces
      psychological distance concept into the research of organizational behavior,
      which can define the concept of psychological distance between employees and an
      organization and describe a level of perceived correspondence or interaction
      between subjects and objects. We developed an employee-organization psychological
      distance (EOPD) scale through both qualitative and quantitative analysis methods.
      As indicated by the research results based on grounded theory (10 employee in
      depth interview records and 277 opening questionnaires) and formal investigation
      (544 questionnaires), this scale consists of six dimensions: experiential
      distance, behavioral distance, emotional distance, cognitive distance, spatial
      temporal distance, and objective social distance based on 44 items. Finally, we
      determined that the EOPD scale exhibited acceptable reliability and validity
      using confirmatory factor analysis. This research may establish a foundation for
      future research on the measurement of psychological relationships between
      employees and organizations.

PMID- 29375428
TI  - An Intervention to Optimize Coach Motivational Climates and Reduce Athlete
      Willingness to Dope (CoachMADE): Protocol for a Cross-Cultural Cluster Randomized
      Control Trial.
AB  - Field-based anti-doping interventions in sport are scarce and focus on athletes.
      However, coaches are recognized as one of the most significant source of
      influence in terms of athletes' cognitions, affect, and behavior. In this paper,
      we present the protocol for a cluster randomized control trial which aims to
      contrast the relative effects of a 'motivation and anti-doping' intervention
      program for coaches against an information-based anti-doping control program. In
      developing the motivation content of our intervention, we drew from Self
      Determination Theory. The project is currently ongoing in Australia and has
      recently started in the United Kingdom and Greece. We aim to recruit 120 coaches
      and approximately 1200 of their athletes across the three countries. Various
      assessments will be taken from both coaches and athletes prior to the
      intervention, immediately after the 12-week intervention and at a 2-month follow
      up. The intervention comprises face-to-face workshops and weekly activities which
      are supported by printed and online material. The project aims to identify
      communication strategies that coaches can use to support athletes' motivation in
      sport and also to promote self-determined reasons for athletes to comply with
      doping regulations. Trial Registration: The trial is registered with the
      Australia and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616001688471.

PMID- 29375429
TI  - Can Music Foster Learning - Effects of Different Text Modalities on Learning and
      Information Retrieval.
AB  - This study investigates the possibilities of fostering learning based on
      differences in recall and comprehension after learning with texts which were
      presented in one of three modalities: either in a spoken, written, or sung
      version. All three texts differ regarding their processing, especially when
      considering working memory. Overall, we assume the best recall performance after
      learning with the written text and the best comprehension performance after
      learning with the sung text, respectively, compared to both other text
      modalities. We also analyzed whether the melody of the sung material functions as
      a mnemonic aid for the learners in the sung text condition. If melody and text of
      the sung version are closely linked, presentation of the melody during the post
      test phase could foster text retrieval. 108 students either learned from a sung
      text performed by a professional singer, a printed text, or the same text read
      out loud. Half of the participants worked on the post-test while listening to the
      melody used for the musical learning material and the other half did not listen
      to a melody. The written learning modality led to significantly better recall
      than with the spoken (d = 0.97) or sung text (d = 0.78). However, comprehension
      after learning with the sung modality was significantly superior compared to when
      learning with the written learning modality (d = 0.40). Reading leads to more
      focus on details, which is required to answer recall questions, while listening
      fosters a general understanding of the text, leading to higher levels of
      comprehension. Listening to the melody during the post-test phase negatively
      affected comprehension, irrespective of the modality during the learning phase.
      This can be explained by the seductive detail effect, as listening to the melody
      during the post-test phase may distract learners from their main task. In
      closing, theoretical and practical implications are discussed.

PMID- 29375431
TI  - A Computerized Version of the Scrambled Sentences Test.
AB  - The scrambled sentences test (SST), an experimental procedure that involves
      participants writing down their cognitions, has been used to elicit individual
      differences in depressiveness and vulnerability to depression. We describe here a
      modification of the SST to adapt it to computerized administration, with a
      particular view of its use in large samples and functional neuroimaging
      applications. In a first study with the computerized version, we reproduce the
      preponderance of positive cognitions in the healthy and the inverse association
      of these cognitions with individual measures of depressiveness. We also report a
      tendency of self-referential cognitions to elicit higher positive cognition
      rates. In a second study, we describe the patterns of neural activations elicited
      by emotional and neutral sentences in a functional neuroimaging study, showing
      that it replicates and extends previous findings obtained with the original
      version of the SST. During the formation of emotional cognitions, ventral areas
      such as the ventral anterior cingulus and the supramarginal gyrus were relatively
      activated. This activation pattern speaks for the recruitment of mechanisms
      coordinating motivational and associative processes in the formation of value
      based decisions.

PMID- 29375430
TI  - Altered Neural Activity during Irony Comprehension in Unaffected First-Degree
      Relatives of Schizophrenia Patients-An fMRI Study.
AB  - Irony is a type of figurative language in which the literal meaning of the
      expression is the opposite of what the speaker intends to communicate. Even
      though schizophrenic patients are known as typically impaired in irony
      comprehension and in the underlying neural functions, to date no one has explored
      the neural correlates of figurative language comprehension in first-degree
      relatives of schizophrenic patients. In the present study, we examined the neural
      correlates of irony understanding in schizophrenic patients and in unaffected
      first-degree relatives of patients compared to healthy adults with functional
      MRI. Our aim was to investigate if possible alterations of the neural circuits
      supporting irony comprehension in first-degree relatives of patients with
      schizophrenia would fulfill the familiality criterion of an endophenotype. We
      examined 12 schizophrenic patients, 12 first-degree relatives of schizophrenia
      patients and 12 healthy controls with functional MRI while they were performing
      irony and control tasks. Different phases of irony processing were examined, such
      as context processing and ironic statement comprehension. Patients had
      significantly more difficulty understanding irony than controls or relatives.
      Patients also showed markedly different neural activation pattern compared to
      controls in both stages of irony processing. Although no significant differences
      were found in the performance of the irony tasks between the control group and
      the relative group, during the fMRI analysis, the relatives showed stronger brain
      activity in the left dorsolateral prefrontal cortex during the context processing
      phase of irony tasks than the control group. However, the controls demonstrated
      higher activations in the left dorsomedial prefrontal cortex and in the right
      inferior frontal gyrus during the ironic statement phase of the irony tasks than
      the relative group. Our results show that despite good task performance, first
      degree relatives of schizophrenia patients had alterations in the neural circuits
      during irony processing. Thus, we suggest that neural alteration of irony
      comprehension could be a potential endophenotypic marker of schizophrenia.

PMID- 29375432
TI  - The Confluence of Perceiving and Thinking in Consciousness Phenomenology.
AB  - The processual relation of thinking and perceiving shall be examined from a
      historical perspective as well as on the basis of methodically conducted first
      person observation. Historically, these two psychological aspects of human
      knowledge and corresponding philosophical positions have predominant alternating
      phases. At certain historical points, thinking and perceiving tend to converge,
      while in the interim phases they seem to diverge with an emphasis on one of them.
      While at the birth of modern science, for instance, these two forms of mental
      life were deeply interlinked, today they seem to be separated more than ever
      before - as a number of scientific crises have shown. Turning from the outer to
      the inner aspect of this issue, a phenomenological view becomes relevant. In
      terms of the consciousness phenomenology developed by Steiner (1861-1925) and
      Witzenmann's (1905-1988) Structure Phenomenology, this article will show how a
      methodical integration of thinking and perceiving can be carried out on the basis
      of first-person observation. In the course of a skilled introspective or
      meditative self-observation the individual's own mental micro-actions of
      separating and integrating come into view, jointly constituting what we usually
      call thinking and perceiving. Consequently, this approach includes a conceptual
      as well as a perceptual dimension the experimental confluence of which ties in
      with the methodological core principle of modern natural science. At the same
      time, making this principle explicit may open the way to a further development of
      human consciousness and its scientific delineation.

PMID- 29375434
TI  - The Effects of Organizational Justice on Positive Organizational Behavior:
      Evidence from a Large-Sample Survey and a Situational Experiment.
AB  - Employees' positive organizational behavior (POB) is not only to promote
      organizational function but also improve individual and organizational
      performance. As an important concept in organizational research, organizational
      justice is thought to be a universal predictor of employee and organizational
      outcomes. The current set of two studies examined the effects of organizational
      justice (OJ) on POB of employees with two different studies, a large-sample
      survey and a situational experiment. In study 1, a total of 2,566 employees from
      45 manufacturing enterprises completed paper-and-pencil questionnaires assessing
      organizational justice (OJ) and positive organizational behavior (POB) of
      employees. In study 2, 747 employees were randomly sampled to participate in the
      situational experiment with 2 * 2 between-subjects design. They were asked to
      read one of the four situational stories and to image that this situation happen
      to the person in the story or them, and then they were asked to imagine how the
      person in the story or they would have felt and what the person or they
      subsequently would have done. The results of study 1 suggested that OJ was
      correlated with POB of employees and OJ is a positive predictor of POB. The
      results of study 2 suggested that OJ had significant effects on POB and negative
      organizational behavior (NOB). Procedural justice accounted for significantly
      more variance than distributive justice in POB of employees. Distributive justice
      and procedural justice have different influences on POB and NOB in terms of
      effectiveness and direction. The effect of OJ on POB was greater than that of
      NOB. In addition, path analysis indicated that the direct effect of OJ on POB was
      smaller than its indirect effect. Thus, many intermediary effects could possibly
      be between them.

PMID- 29375433
TI  - Trajectories of Early Childhood Developmental Skills and Early Adolescent
      Psychotic Experiences: Findings from the ALSPAC UK Birth Cohort.
AB  - Objective: The aim of this study was to use prospective data from the Avon
      Longitudinal Study of Parents and Children (ALSPAC) to examine association
      between trajectories of early childhood developmental skills and psychotic
      experiences (PEs) in early adolescence. Method: This study examined data from n =
      6790 children from the ALSPAC cohort who participated in a semi-structured
      interview to assess PEs at age 12. Child development was measured using parental
      report at 6, 18, 30, and 42 months of age using a questionnaire of items adapted
      from the Denver Developmental Screening Test - II. Latent class growth analysis
      was used to generate trajectories over time for measures of fine and gross motor
      development, social, and communication skills. Logistic regression was used to
      investigate associations between developmental trajectories in each of these
      early developmental domains and PEs at age 12. Results: The results provided
      evidence that decline rather than enduringly poor social (adjusted OR = 1.28, 95%
      CI = 1.10-1.92, p = 0.044) and communication skills (adjusted OR 1.12, 95% CI =
      1.03-1.22, p = 0.010) is predictive of suspected or definite PEs in early
      adolescence, than those with stable and/or improving skills. Motor skills did not
      display the same pattern of association; although gender specific effects
      provided evidence that only declining pattern of fine motor skills was associated
      with suspected and definite PEs in males compared to females (interaction OR =
      1.47, 95% CI = 1.09-1.97, p = 0.012). Conclusion: Findings suggest that decline
      rather than persistent impairment in social and communication skills were most
      predictive of PEs in early adolescence. Findings are discussed in terms of
      study's strengths, limitations, and clinical implications.

PMID- 29375435
TI  - An Experimental Evaluation of Competing Age-Predictions of Future Time
      Perspective between Workplace and Retirement Domains.
AB  - Future time perspective (FTP) is defined as "perceptions of the future as being
      limited or open-ended" (Lang and Carstensen, 2002; p. 125). The construct figures
      prominently in both workplace and retirement domains, but the age-predictions are
      competing: Workplace research predicts decreasing FTP age-change, in contrast,
      retirement scholars predict increasing FTP age-change. For the first time, these
      competing predictions are pitted in an experimental manipulation of subjective
      life expectancy (SLE). A sample of N = 207 older adults (age 45-60) working full
      time (>30-h/week) were randomly assigned to SLE questions framed as either 'Live
      to' or 'Die-by' to evaluate competing predictions for FTP. Results indicate
      general support for decreasing age-change in FTP, indicated by independent-sample
      t-tests showing lower FTP in the 'Die-by' framing condition. Further general
      linear model analyses were conducted to test for interaction effects of
      retirement planning with experimental framings on FTP and intended retirement;
      While retirement planning buffered FTP's decrease, simple-effects also revealed
      that retirement planning increased intentions for sooner retirement, but lack of
      planning increased intentions for later retirement. Discussion centers on
      practical implications of our findings and consequences validity evidence in
      future empirical research of FTP in both workplace and retirement domains.

PMID- 29375436
TI  - How Person-Organization Fit Impacts Employees' Perceptions of Justice and Well
      Being.
AB  - Regulatory fit theory predicts that when individuals adopt strategies that
      sustain their motivational orientations, they feel right about what is happening.
      Our aim was to test these predictions at the person-organization level. Across
      three studies, we expected and found that a feeling right experience that results
      from a match between an employee and an organizational climate produces
      perceptions that the company's prevailing procedures are fair. In Study 1 (N =
      300), a survey among employees of distinct companies, we observed that the more
      organizational characteristics matched individual promotion and prevention focus
      of the employees, the more the employees perceived their workplace as just. Study
      2 (N = 139), a randomized-control experiment, replicated this pattern by
      demonstrating that individuals with a predominant promotion focus assigned
      fairness to the organizational conduct most strongly when they recalled events
      characterizing a promotion-oriented environment; on the contrary, individuals
      with a predominant prevention focus deemed their workplace most fair when they
      were asked to recall prevention-related conduct of their company. In Study 3 (N =
      376), a cross-sectional field study, we found that regulatory non-fit was
      associated with lower procedural justice perceptions and this, in turn, related
      to higher burnout. Theoretical and practical implications of applying regulatory
      fit theory to person-organization relationships are discussed.

PMID- 29375437
TI  - Residents' Dissatisfaction and All-Cause Mortality. Evidence from 74 European
      Cities.
AB  - Background: About 2/3 of the Europeans reside in cities. Thus, we must expand our
      knowledge on how city characteristics affect health and well-being. Perceptions
      about cities' resources and functioning might be related with health, as they
      capture subjective experiences of the residents. We characterized the health
      status of 74 European cities, using all-cause mortality as indicator, and
      investigated the association of mortality with residents' dissatisfaction with
      key domains of urban living. Methods: We considered 74 European cities from 29
      countries. Aggregated data on residents' dissatisfaction was obtained from the
      Flash Eurobarometer, Quality of life in European cities (2004-2015). For each
      city a global dissatisfaction score and a dissatisfaction score by domain
      (environment, social, economic, healthcare, and infrastructures/services) were
      calculated. Data on mortality and population was obtained from the Eurostat.
      Standardized Mortality Ratios, SMR, and 95% Confidence Intervals (95% CI) were
      calculated. The association between dissatisfaction scores and SMR was estimated
      using Generalized Linear Models. Results: SMR varied markedly (range: 73.2
      146.5), being highest in Eastern Europe and lowest in the South and Western
      European cities. Residents' dissatisfaction levels also varied greatly. We found
      a significant association between city SMR and residents' dissatisfaction with
      healthcare (beta = 0.334; IC 95% 0.030-0.639) and social environment (beta =
      0.239; IC 95% 0.015-0.464). No significant association was found with the
      dissatisfaction scores related with the physical and economic environment and the
      infrastructures/services. Conclusions: We found a significant association between
      city levels of mortality and residents' dissatisfaction with certain urban
      features, suggesting subjective assessments can be also used to comprehend urban
      health.

PMID- 29375438
TI  - Measuring Perceptual Consciousness.

PMID- 29375439
TI  - Association between Social Anxiety and Visual Mental Imagery of Neutral Scenes:
      The Moderating Role of Effortful Control.
AB  - According to cognitive theories, verbal processing attenuates emotional
      processing, whereas visual imagery enhances emotional processing and contributes
      to the maintenance of social anxiety. Individuals with social anxiety report
      negative mental images in social situations. However, the general ability of
      visual mental imagery of neutral scenes in individuals with social anxiety is
      still unclear. The present study investigated the general ability of non
      emotional mental imagery (vividness, preferences for imagery vs. verbal
      processing, and object or spatial imagery) and the moderating role of effortful
      control in attenuating social anxiety. The participants (N = 231) completed five
      questionnaires. The results showed that social anxiety was not necessarily
      associated with all aspects of mental imagery. As suggested by theories, social
      anxiety was not associated with a preference for verbal processing. However,
      social anxiety was positively correlated with the visual imagery scale,
      especially the object imagery scale, which concerns the ability to construct
      pictorial images of individual objects. Further, it was negatively correlated
      with the spatial imagery scale, which concerns the ability to process information
      about spatial relations between objects. Although object imagery and spatial
      imagery positively and negatively predicted the degree of social anxiety,
      respectively, these effects were attenuated when socially anxious individuals had
      high effortful control. Specifically, in individuals with high effortful control,
      both object and spatial imagery were not associated with social anxiety. Socially
      anxious individuals might prefer to construct pictorial images of individual
      objects in natural scenes through object imagery. However, even in individuals
      who exhibit these features of mental imagery, effortful control could inhibit the
      increase in social anxiety.

PMID- 29375440
TI  - An Analysis of the Associations among Cognitive Impulsiveness, Reasoning Process,
      and Rational Decision Making.
AB  - Impulsivity may lead to several unfortunate consequences and maladaptive
      behaviors for both clinical and nonclinical people. It has a key role in many
      forms of psychopathology. Although literature has discussed the negative impact
      of impulsivity, few have emphasized the relationship between cognitive
      impulsiveness and decision making. The aim of this study is to investigate the
      effects of cognitive impulsiveness on decision making and explore the strategies
      used by participants to solve problems. For this purpose, we apply two measures
      of impulsivity: the self-report Barratt Impulsiveness Scale (BIS-11) and the
      performance based Cognitive Reflection Test (CRT). Moreover, we evaluate
      participants' reasoning processes employed to answer CRT questions based on the
      calculation expressions, data organization, and erasures they made while
      answering the CRT (note that we utilized the instruments using pen and paper).
      These reasoning processes are related to the role of executive functions in
      decision making, and its relationship with impulsiveness. The sample consists of
      191 adults, who were either professionals or undergraduate students from the
      fields of business, management, or accounting. The results show that cognitive
      impulsiveness may negatively affect decision making, and that those who presented
      the calculation to answer the CRT questions made better decisions. Moreover,
      there was no difference in the strategies used by impulsive vs. nonimpulsive
      participants during decision making. Finally, people who inhibited their
      immediate answers to CRT questions performed better during decision making.

PMID- 29375441
TI  - Comparing Repetition Priming Effects in Words and Arithmetic Equations: Robust
      Priming Regardless of Color or Response Hand Change.
AB  - Previous studies have shown that stimulus repetition can lead to reliable
      behavioral improvements. Although this repetition priming (RP) effect has been
      reported in a number of paradigms using a variety of stimuli including words,
      objects, and faces, only a few studies have investigated mathematical cognition
      involving arithmetic computation, and no prior research has directly compared RP
      effects in a linguistic task with an arithmetic task. In two experiments, we used
      a within-subjects design to investigate and compare the magnitude of RP, and the
      effects of changing the color or the response hand for repeated, otherwise
      identical, stimuli in a word and an arithmetic categorization task. The results
      show that the magnitude of RP was comparable between the two tasks and that
      changing the color or the response hand had a negligible effect on priming in
      either task. These results extended previous findings in mathematical cognition.
      They also indicate that priming does not vary with stimulus domain. The
      implications of the results were discussed with reference to both facilitation of
      component processes and episodic memory retrieval of stimulus-response binding.

PMID- 29375443
TI  - Commentary: Mental Toughness and Individual Differences in Learning, Educational
      and Work Performance, Psychological Well-being, and Personality: A Systematic
      Review.

PMID- 29375442
TI  - Computer-Based Training in Math and Working Memory Improves Cognitive Skills and
      Academic Achievement in Primary School Children: Behavioral Results.
AB  - Student academic achievement has been positively related to further development
      outcomes, such as the attainment of higher educational, employment, and
      socioeconomic aspirations. Among all the academic competences, mathematics has
      been identified as an essential skill in the field of international leadership as
      well as for those seeking positions in disciplines related to science,
      technology, and engineering. Given its positive consequences, studies have
      designed trainings to enhance children's mathematical skills. Additionally, the
      ability to regulate and control actions and cognitions, i.e., executive functions
      (EF), has been associated with school success, which has resulted in a strong
      effort to develop EF training programs to improve students' EF and academic
      achievement. The present study examined the efficacy of a school computer-based
      training composed of two components, namely, working memory and mathematics
      tasks. Among the advantages of using a computer-based training program is the
      ease with which it can be implemented in school settings and the ease by which
      the difficulty of the tasks can be adapted to fit the child's ability level. To
      test the effects of the training, children's cognitive skills (EF and IQ) and
      their school achievement (math and language grades and abilities) were evaluated.
      The results revealed a significant improvement in cognitive skills, such as non
      verbal IQ and inhibition, and better school performance in math and reading among
      the children who participated in the training compared to those children who did
      not. Most of the improvements were related to training on WM tasks. These
      findings confirmed the efficacy of a computer-based training that combined WM and
      mathematics activities as part of the school routines based on the training's
      impact on children's academic competences and cognitive skills.

PMID- 29375444
TI  - Perspectives on Early Power Mobility Training, Motivation, and Social
      Participation in Young Children with Motor Disabilities.
AB  - The efficacy of traditional training programs (e.g., neurodevelopmental therapy)
      in promoting independent mobility and early child development across all three
      International Classification of Functioning, Disability, and Health levels lacks
      rigorous research support. Therefore, early power mobility training needs to be
      considered as a feasible intervention for very young children who are unlikely to
      achieve independent mobility. This perspective article has three aims: (1) to
      provide empirical evidence of differences in early independent mobility,
      motivation, daily life activities, and social participation between young
      children with typical development and motor disabilities; (2) to discuss the
      contemporary concepts of and approaches to early power mobility training for
      young children with motor disabilities and the current need for changes to such
      training; and (3) to provide recommendations for early power mobility training in
      pediatric rehabilitation. Independent mobility is critical for social
      participation; therefore, power mobility can be accessible and implemented as
      early as possible, specifically for infants who are at risk for mobility or
      developmental delay. To maximize the positive effects of independent mobility on
      children's social participation, early power mobility training must consider
      their levels of functioning, the amount of exploration and contextual factors,
      including individual and environmental factors.

PMID- 29375445
TI  - EMDR as Add-On Treatment for Psychiatric and Traumatic Symptoms in Patients with
      Substance Use Disorder.
AB  - Background: Substance use disorders (SUD) are patterns of substance use leading
      to severe impairment on social, working and economic levels. In vivo and clinical
      findings have enhanced the role of the brain's stress-related system in
      maintaining SUD behaviors. Several studies have also revealed a high prevalence
      of post-traumatic symptoms among SUD patients, suggesting that a trauma-informed
      treatment approach could lead to better treatment outcomes. However, only few
      studies have evaluated the use of eye movement desensitization and reprocessing
      (EMDR) in SUD without consistent results. The aim of the present pilot study was
      to assess the efficacy of a combined trauma-focused (TF) and addiction-focused
      (AF) EMDR intervention in treating post-traumatic and stress-related symptoms of
      patients with SUD. Methods: Forty patients with different SUD were enrolled in
      the study. Twenty patients underwent treatment as usual (TAU), the other 20
      patients were treated with TAU plus 24 weekly sessions of EMDR. All patients were
      assessed before and after intervention for several psychological dimensions using
      specific tools (i.e., BDI-II, DES, IES-R, STAI, and SCL-90-GSI). A repeated
      measure MANOVA was performed to evaluate both between groups (TAU + EMDR vs. TAU)
      and within group (pre- vs. post-intervention) effects and interactions. A
      secondary outcome was the dichotomous variable yielded by the urine drug testing
      immunoassay (yes/no). Results: The RM-MANOVA revealed both a significant pre-post
      main effect (p < 0.001), and a significant group-by-time main effect (p < 0.001).
      Significant improvements on IES-R, DES, and SCL-90-GSI scales were shown in both
      groups according to time effects (p < 0.05). However, significant greater effects
      were found for TAU + EMDR group than TAU group. No differences were found between
      TAU and TAU + EMDR groups in terms of urine drug immunoassay results before and
      after the interventions. Conclusions: The TAU + EMDR group showed a significant
      improvement of post-traumatic and dissociative symptoms, accompanied by a
      reduction in anxiety and overall psychopathology levels, whereas TAU group showed
      a significant reduction only in post-traumatic symptoms. Although our results can
      only be considered preliminary, this study suggests that a combined TF- and AF-
      EMDR protocol is an effective and well-accepted add-on treatment for patients
      with SUD.

PMID- 29375446
TI  - Emotional Arousal at Memory Encoding Enhanced P300 in the Concealed Information
      Test.
AB  - Previous studies have reported that the concealed information test (CIT) is a
      reliable and powerful method for detecting information. However, the external
      validity of the CIT studies has not been fully proven. In particular, few studies
      have examined the effects of emotional arousal at memory encoding on
      physiological responses in the CIT. The present study investigated the influence
      on the CIT of the magnitude of emotional arousal at memory encoding of a mock
      crime, using the P300 component of the event-related brain potential (ERP). In
      accord with the assumptions of excitation-transfer theory, we presented
      emotionally arousing pictures before a mock crime. Participants were randomly
      assigned to either a high emotional arousal group (n = 10) or a low emotional
      arousal group (n = 11), viewing pictures expected to arouse emotion at a high or
      low level, respectively. Subsequently, all participants enacted the same mock
      crime, in which they were instructed to stab a pillow with a sharp-edged tool
      (e.g., a kitchen knife or ice pick) as if harassing a mannequin lying on a bed.
      After the antecedent emotional experience, the P300-based CIT was conducted.
      Participants in the high arousal group showed significantly greater P300
      amplitudes in response to a probe stimulus compared with the low arousal group.
      No differences were found between the groups in response to irrelevant stimuli.
      These results support the notion that emotional arousal influences the P300 in
      the CIT paradigm.

PMID- 29375447
TI  - Burnout, Depression, and Borderline Personality: A 1,163-Participant Study.
AB  - We examined the association of burnout with borderline personality (BP) traits in
      a study of 1,163 educational staff (80.9% women; mean age: 42.96). Because
      burnout has been found to overlap with depression, parallel analyses of burnout
      and depression were conducted. Burnout symptoms were assessed with the Shirom
      Melamed Burnout Measure, depressive symptoms with the PHQ-9, and BP traits with
      the Borderline Personality Questionnaire. Burnout was found to be associated with
      BP traits, controlling for neuroticism and history of depressive disorders. In
      women, burnout was linked to both the "affective insecurity" and the
      "impulsiveness" component of BP. In men, only the link between burnout and
      "affective insecurity" reached statistical significance. Compared to participants
      with "low" BP scores, participants with "high" BP scores reported more burnout
      symptoms, depressive symptoms, neuroticism, and occupational stress and less
      satisfaction with life. Disattenuated correlations between burnout and depression
      were close to 1, among both women (0.91) and men (0.94). The patterns of
      association of burnout and depression with the main study variables were similar,
      pointing to overlapping nomological networks. Burnout symptoms were only partly
      attributed to work by our participants. Our findings suggest that burnout is
      associated with BP traits through burnout-depression overlap.

PMID- 29375448
TI  - Social Context Disambiguates the Interpretation of Laughter.
AB  - Despite being a pan-cultural phenomenon, laughter is arguably the least
      understood behaviour deployed in social interaction. As well as being a response
      to humour, it has other important functions including promoting social
      affiliation, developing cooperation and regulating competitive behaviours. This
      multi-functional feature of laughter marks it as an adaptive behaviour central to
      facilitating social cohesion. However, it is not clear how laughter achieves this
      social cohesion. We consider two approaches to understanding how laughter
      facilitates social cohesion - the 'representational' approach and the 'affect
      induction' approach. The representational approach suggests that laughter conveys
      information about the expresser's emotional state, and the listener decodes this
      information to gain knowledge about the laugher's felt state. The affect
      induction approach views laughter as a tool to influence the affective state of
      listeners. We describe a modified version of the affect-induction approach, in
      which laughter is combined with additional factors - including social context,
      verbal information, other social signals and knowledge of the listener's
      emotional state - to influence an interaction partner. This view asserts that
      laughter by itself is ambiguous: the same laughter may induce positive or
      negative affect in a listener, with the outcome determined by the combination of
      these additional factors. Here we describe two experiments exploring which of
      these approaches accurately describes laughter. Participants judged the
      genuineness of audio-video recordings of social interactions containing laughter.
      Unknown to the participants the recordings contained either the original laughter
      or replacement laughter from a different part of the interaction. When
      replacement laughter was matched for intensity, genuineness judgements were
      similar to judgements of the original unmodified recordings. When replacement
      laughter was not matched for intensity, genuineness judgements were generally
      significantly lower. These results support the affect-induction view of laughter
      by suggesting that laughter is inherently underdetermined and ambiguous, and that
      its interpretation is determined by the context in which it occurs.

PMID- 29375449
TI  - Grade Expectations: Rationality and Overconfidence.
AB  - Confidence and overconfidence are essential aspects of human nature, but
      measuring (over)confidence is not easy. Our approach is to consider students'
      forecasts of their exam grades. Part of a student's grade expectation is based on
      the student's previous academic achievements; what remains can be interpreted as
      (over)confidence. Our results are based on a sample of about 500 second-year
      undergraduate students enrolled in a statistics course in Moscow. The course
      contains three exams and each student produces a forecast for each of the three
      exams. Our models allow us to estimate overconfidence quantitatively. Using these
      models we find that students' expectations are not rational and that most
      students are overconfident, in agreement with the general literature. Less
      obvious is that overconfidence helps: given the same academic achievement
      students with larger confidence obtain higher exam grades. Female students are
      less overconfident than male students, their forecasts are more rational, and
      they are also faster learners in the sense that they adjust their expectations
      more rapidly.

PMID- 29375450
TI  - Friendly Home and Inhabitants' Morality: Mutual Relationships.
AB  - The study is aimed at investigating the connection between the friendliness of
      the home environment and the moral motives' level. The friendliness of the home
      environment includes two aspects: the number of functions provided by home
      (functionality) and the congruence of these functions with inhabitants' needs
      (relevance). The theoretical framework of the study was formed by research and
      ideas emphasizing the interplay between people and their environments. We
      hypothesized that the friendliness of the home environment and inhabitants' moral
      motives would have a reciprocal relationship: the friendlier the home the higher
      the inhabitants' moral motives' level, and, vice versa, the higher the person's
      moral motives' level the more positive home image. The respondents were 550
      students (25% male). The Home Environment Functionality Questionnaire, the Home
      Environment Relevance Questionnaire, and the Moral Motivation Model Scale were
      used. As expected, it was found that the friendliness of the home environment and
      the inhabitants' moral motives are in reciprocal synergetic relationships.
      Relevance formed more nuanced correlation patterns with moral motives than
      functionality did. Functionality predicted moral motives poorly whereas moral
      motives predicted functionality strongly. Finally, relevance and moral motives
      were found to be in mutual relationships whereas the perceived functionality was
      predicted by moral motives only.

PMID- 29375451
TI  - Acceptance and Commitment Therapy for Health Behavior Change: A Contextually
      Driven Approach.
AB  - Promoting health behavior change presents an important challenge to theory and
      research in the field of health psychology. In this paper, we introduce a context
      driven approach, the Acceptance and Commitment Therapy (ACT) model which is built
      on Relational Frame Theory. The ACT-based intervention aims to promote
      individuals' new health behavior patterns through the improvement of the key
      construct of psychological flexibility, which is defined as the ability to
      contact the present moment more fully with acceptance and mindfulness as a
      conscious human being. Building on the psychological flexibility model,
      implemented through the six core ACT processes, individuals improve maintenance
      of long term health behavior change through committed acts in service of chosen
      values while acknowledging and accepting the existence of contrary thoughts,
      rules, and emotions as part of themselves but not determinant of their behaviors.
      Taking advantage of this context-driven approach of health behavior change, we
      recommend researchers and practitioners to design their health behavior change
      intervention programs based on ACT.

PMID- 29375452
TI  - The Effects of Lexical Pitch Accent on Infant Word Recognition in Japanese.
AB  - Learners of lexical tone languages (e.g., Mandarin) develop sensitivity to tonal
      contrasts and recognize pitch-matched, but not pitch-mismatched, familiar words
      by 11 months. Learners of non-tone languages (e.g., English) also show a tendency
      to treat pitch patterns as lexically contrastive up to about 18 months. In this
      study, we examined if this early-developing capacity to lexically encode pitch
      variations enables infants to acquire a pitch accent system, in which pitch-based
      lexical contrasts are obscured by the interaction of lexical and non-lexical
      (i.e., intonational) features. Eighteen 17-month-olds learning Tokyo Japanese
      were tested on their recognition of familiar words with the expected pitch or the
      lexically opposite pitch pattern. In early trials, infants were faster in
      shifting their eyegaze from the distractor object to the target object than in
      shifting from the target to distractor in the pitch-matched condition. In later
      trials, however, infants showed faster distractor-to-target than target-to
      distractor shifts in both the pitch-matched and pitch-mismatched conditions. We
      interpret these results to mean that, in a pitch-accent system, the ability to
      use pitch variations to recognize words is still in a nascent state at 17 months.

PMID- 29375453
TI  - Understanding Freshness Perception from the Cognitive Mechanisms of Flavor: The
      Case of Beverages.
AB  - Freshness perception has received recent consideration in the field of consumer
      science mainly because of its hedonic dimension, which is assumed to influence
      consumers' preference and behavior. However, most studies have considered
      freshness as a multisensory attribute of food and beverage products without
      investigating the cognitive mechanisms at hand. In the present review, we endorse
      a slightly different perspective on freshness. We focus on (i) the multisensory
      integration processes that underpin freshness perception, and (ii) the top-down
      factors that influence the explicit attribution of freshness to a product by
      consumers. To do so, we exploit the recent literature on the cognitive
      underpinnings of flavor perception as a heuristic to better characterize the
      mechanisms of freshness perception in the particular case of beverages. We argue
      that the lack of consideration of particular instances of flavor, such as
      freshness, has resulted in a lack of consensus about the content and structure of
      different types of flavor representations. We then enrich these theoretical
      analyses, with a review of the cognitive mechanisms of flavor perception: from
      multisensory integration processes to the influence of top-down factors (e.g.,
      attentional and semantic). We conclude that similarly to flavor, freshness
      perception is characterized by hybrid content, both perceptual and semantic, but
      that freshness has a higher-degree of specificity than flavor. In particular,
      contrary to flavor, freshness is characterized by specific functions (e.g.,
      alleviation of oropharyngeal symptoms) and likely differs from flavor with
      respect to the weighting of each sensory contributor, as well as to its
      subjective location. Finally, we provide a comprehensive model of the cognitive
      mechanisms that underlie freshness perception. This model paves the way for
      further empirical research on particular instances of flavor, and will enable
      advances in the field of food and beverage cognition.

PMID- 29375454
TI  - When Do Morally Motivated Innovators Elicit Inspiration Instead of Irritation?
AB  - Innovators (i.e., consumers who are the first to adopt an innovation) are pivotal
      for the societal diffusion of sustainable innovations. But when are innovators
      most influential? Recent work suggests that morally motivated innovators (i.e.,
      consumers who adopt an innovation out of concern for the welfare of others) can
      make fellow consumers who have not yet adopted that innovation feel morally
      inadequate. As a self-defense mechanism, those fellow consumers might dismiss
      these innovators and their choices. As a result, ironically, morally motivated
      innovators might discourage others to adopt sustainable innovations. In an
      experimental study, we replicate this pattern, but also show that moral
      innovators can elicit a more positive response as well. Specifically, our results
      offer initial evidence that morally motivated innovators may be more inspiring
      than self-interested innovators, provided that their actions do not directly pose
      a threat to the moral self-concept of observers. In sum, our research sheds
      empirical light on the conditions under which innovators are likely to
      facilitate, rather than slow down the transition to a more sustainable society.

PMID- 29375455
TI  - Test-Retest Reliability of Measures Commonly Used to Measure Striatal Dysfunction
      across Multiple Testing Sessions: A Longitudinal Study.
AB  - Cognitive impairment is common amongst many neurodegenerative movement disorders
      such as Huntington's disease (HD) and Parkinson's disease (PD) across multiple
      domains. There are many tasks available to assess different aspects of this
      dysfunction, however, it is imperative that these show high test-retest
      reliability if they are to be used to track disease progression or response to
      treatment in patient populations. Moreover, in order to ensure effects of
      practice across testing sessions are not misconstrued as clinical improvement in
      clinical trials, tasks which are particularly vulnerable to practice effects need
      to be highlighted. In this study we evaluated test-retest reliability in mean
      performance across three testing sessions of four tasks that are commonly used to
      measure cognitive dysfunction associated with striatal impairment: a combined
      Simon Stop-Signal Task; a modified emotion recognition task; a circle tracing
      task; and the trail making task. Practice effects were seen between sessions 1
      and 2 across all tasks for the majority of dependent variables, particularly
      reaction time variables; some, but not all, diminished in the third session. Good
      test-retest reliability across all sessions was seen for the emotion recognition,
      circle tracing, and trail making test. The Simon interference effect and stop
      signal reaction time (SSRT) from the combined-Simon-Stop-Signal task showed
      moderate test-retest reliability, however, the combined SSRT interference effect
      showed poor test-retest reliability. Our results emphasize the need to use
      control groups when tracking clinical progression or use pre-baseline training on
      tasks susceptible to practice effects.

PMID- 29375456
TI  - Self-face Captures, Holds, and Biases Attention.
AB  - The implicit self-recognition process may take place already in the pre-attentive
      stages of perception. After a silent stimulus has captured attention, it is
      passed on to the attentive stage where it can affect decision making and
      responding. Numerous studies show that the presence of self-referential
      information affects almost every cognitive level. These effects may share a
      common and fundamental basis in an attentional mechanism, conceptualized as
      attentional bias: the exaggerated deployment of attentional resources to a
      salient stimulus. A gold standard in attentional bias research is the dot-probe
      paradigm. In this task, a prominent stimulus (cue) and a neutral stimulus are
      presented in different spatial locations, followed by the presentation of a
      target. In the current study we aimed at investigating whether the self-face
      captures, holds and biases attention when presented as a task-irrelevant
      stimulus. In two dot-probe experiments coupled with the event-related potential
      (ERP) technique we analyzed the following relevant ERPs components: N2pc and SPCN
      which reflect attentional shifts and the maintenance of attention, respectively.
      An inter-stimulus interval separating face-cues and probes (800 ms) was
      introduced only in the first experiment. In line with our predictions, in
      Experiment 1 the self-face elicited the N2pc and the SPCN component. In
      Experiment 2 in addition to N2pc, an attentional bias was observed. Our results
      indicate that unintentional self-face processing disables the top-down control
      setting to filter out distractors, thus leading to the engagement of attentional
      resources and visual short-term memory.

PMID- 29375457
TI  - Self-control in Online Discussions: Disinhibited Online Behavior as a Failure to
      Recognize Social Cues.
AB  - In an online experiment we examined the role of self-control in recognizing
      social cues in the context of disinhibited online behavior (e.g., flaming and
      trolling). We temporarily lowered participants' self-control capacity with an ego
      depletion paradigm (i.e., color Stroop task). Next, we measured participants'
      sensitivity to social cues with an emotional Stroop task containing neutral,
      negative, and taboo words. Sensitivity to social cues is represented by the
      increase in reaction time to negative and especially taboo words compared to
      neutral words. As expected, undepleted participants were slower to process the
      color of negative and taboo words. By contrast, depleted participants (i.e.,
      those with lowered self-control capacity) did not react differently to taboo or
      negative words than they did to neutral words. The experiment illustrates that
      self-control failure may manifest itself in a failure to recognize social cues.
      The finding underlines the importance of self-control in understanding
      disinhibited online behavior: Many instances of disinhibited online behavior may
      occur not because people are unable to control themselves, but because they do
      not realize that a situation calls for self-control in the first place.

PMID- 29375458
TI  - A Systematic Review of Non-Traumatic Spinal Cord Injuries in Sub-Saharan Africa
      and a Proposed Diagnostic Algorithm for Resource-Limited Settings.
AB  - Background: Non-traumatic myelopathy is common in Africa and there are geographic
      differences in etiology. Clinical management is challenging due to the broad
      differential diagnosis and the lack of diagnostics. The objective of this
      systematic review is to determine the most common etiologies of non-traumatic
      myelopathy in sub-Saharan Africa to inform a regionally appropriate diagnostic
      algorithm. Methods: We conducted a systemic review searching Medline and Embase
      databases using the following search terms: "Non traumatic spinal cord injury" or
      "myelopathy" with limitations to epidemiology or etiologies and Sub-Saharan
      Africa. We described the frequencies of the different etiologies and proposed a
      diagnostic algorithm based on the most common diagnoses. Results: We identified
      19 studies all performed at tertiary institutions; 15 were retrospective and 13
      were published in the era of the HIV epidemic. Compressive bone lesions accounted
      for more than 48% of the cases; a majority were Pott's disease and metastatic
      disease. No diagnosis was identified in up to 30% of cases in most studies; in
      particular, definitive diagnoses of non-compressive lesions were rare and a
      majority were clinical diagnoses of transverse myelitis and HIV myelopathy. Age
      and HIV were major determinants of etiology. Conclusion: Compressive myelopathies
      represent a majority of non-traumatic myelopathies in sub-Saharan Africa, and
      most were due to Pott's disease. Non-compressive myelopathies have not been well
      defined and need further research in Africa. We recommend a standardized approach
      to management of non-traumatic myelopathy focused on identifying treatable
      conditions with tests widely available in low-resource settings.

PMID- 29375460
TI  - Spontaneous Intracerebral Hemorrhage: Should We Operate?

PMID- 29375459
TI  - A Comparative Study of Feature Selection Methods for the Discriminative Analysis
      of Temporal Lobe Epilepsy.
AB  - It is crucial to differentiate patients with temporal lobe epilepsy (TLE) from
      the healthy population and determine abnormal brain regions in TLE. The cortical
      features and changes can reveal the unique anatomical patterns of brain regions
      from structural magnetic resonance (MR) images. In this study, structural MR
      images from 41 patients with left TLE, 34 patients with right TLE, and 58 normal
      controls (NC) were acquired, and four kinds of cortical measures, namely cortical
      thickness, cortical surface area, gray matter volume (GMV), and mean curvature,
      were explored for discriminative analysis. Three feature selection methods
      including the independent sample t-test filtering, the sparse-constrained
      dimensionality reduction model (SCDRM), and the support vector machine-recursive
      feature elimination (SVM-RFE) were investigated to extract dominant features
      among the compared groups for classification using the support vector machine
      (SVM) classifier. The results showed that the SVM-RFE achieved the highest
      performance (most classifications with more than 84% accuracy), followed by the
      SCDRM, and the t-test. Especially, the surface area and GMV exhibited prominent
      discriminative ability, and the performance of the SVM was improved significantly
      when the four cortical measures were combined. Additionally, the dominant regions
      with higher classification weights were mainly located in the temporal and the
      frontal lobe, including the entorhinal cortex, rostral middle frontal,
      parahippocampal cortex, superior frontal, insula, and cuneus. This study
      concluded that the cortical features provided effective information for the
      recognition of abnormal anatomical patterns and the proposed methods had the
      potential to improve the clinical diagnosis of TLE.

PMID- 29375461
TI  - In Vivo Tau Imaging for a Diagnostic Platform of Tauopathy Using the rTg4510
      Mouse Line.
AB  - Association of tau deposition with neurodegeneration in Alzheimer's disease (AD)
      and related tau-positive neurological disorders collectively referred to as
      tauopathies indicates contribution of tau aggregates to neurotoxicity. The
      discovery of tau gene mutations in FTDP-17-tau kindreds has provided unequivocal
      evidence that tau abnormalities alone can induce neurodegenerative disorders.
      Therefore, visualization of tau accumulation would offer a reliable, objective
      index to aid in the diagnosis of tauopathy and to assess the disease progression.
      Positron emission tomography (PET) imaging of tau lesions is currently available
      using several tau PET ligands. Because most tau PET ligands have the property of
      an extrinsic fluorescent dye, these ligands are considered to be useful for both
      PET and fluorescence imaging. In addition, small-animal magnetic resonance
      imaging (MRI) is available for both structural and functional imaging. Using
      these advanced imaging techniques, in vivo studies on a mouse model of tauopathy
      will provide significant insight into the translational research of
      neurodegenerative diseases. In this review, we will discuss the utilities of PET,
      MRI, and fluorescence imaging for evaluating the disease progression of
      tauopathy.

PMID- 29375462
TI  - The Applicability of Rhythm-Motor Tasks to a New Dual Task Paradigm for Older
      Adults.
AB  - Given the interplay between cognitive and motor functions during walking,
      cognitive demands required during gait have been investigated with regard to dual
      task performance. Along with the needs to understand how the type of concurrent
      task while walking affects gait performance, there are calls for diversified dual
      tasks that can be applied to older adults with varying levels of cognitive
      decline. Therefore, this study aimed to examine how rhythm-motor tasks affect
      dual task performance and gait control, compared to a traditional cognitive-motor
      task. Also, it examined whether rhythm-motor tasks are correlated with
      traditional cognitive-motor task performance and cognitive measures. Eighteen
      older adults without cognitive impairment participated in this study. Each
      participant was instructed to walk at self-paced tempo without performing a
      concurrent task (single walking task) and walk while separately performing two
      types of concurrent tasks: rhythm-motor and cognitive-motor tasks. Rhythm-motor
      tasks included instrument playing (WalkIP), matching to rhythmic cueing (WalkRC),
      and instrument playing while matching to rhythmic cueing (WalkIP+RC). The
      cognitive-motor task involved counting forward by 3s (WalkCount.f3). In each
      condition, dual task costs (DTC), a measure for how dual tasks affect gait
      parameters, were measured in terms of walking speed and stride length. The ratio
      of stride length to walking speed, a measure for dynamic control of gait, was
      also examined. The results of this study demonstrated that the task type was
      found to significantly influence these measures. Rhythm-motor tasks were found to
      interfere with gait parameters to a lesser extent than the cognitive-motor task
      (WalkCount.f3). In terms of ratio measures, stride length remained at a similar
      level, walking speed greatly decreased in the WalkCount.f3 condition. Significant
      correlations between dual task-related measures during rhythm-motor and cognitive
      motor tasks support the potential of applying rhythm-motor tasks to dual task
      methodology. This study presents how rhythm-motor tasks demand cognitive control
      at different levels than those engaged by cognitive-motor tasks. It also
      indicates how these new dual tasks can effectively mediate dual task performance
      indicative of fall risks, while requiring increased cognitive resources but
      facilitating gait control as a compensatory strategy to maintain gait stability.

PMID- 29375463
TI  - Subjective Positive and Negative Sleep Variables Differentially Affect Cellular
      Immune Activity in a Breast Cancer Survivor: A Time-series Analysis Approach.
AB  - This study on a breast cancer survivor suffering from cancer-related fatigue
      (CaRF) and depression investigated the bidirectional relationship between
      cellular immune activity and subjective sleep. The 49-year-old patient (breast
      cancer diagnosis 5 years before the study, currently in remission) collected her
      full urine output for 28 days in 12-h intervals (8:00 p.m. to 8:00 a.m. and 8:00
      a.m. to 8:00 p.m.). These urine samples were used to determine urinary neopterin
      (cellular immune activation marker) and creatinine concentrations via high
      pressure liquid chromatography (HPLC). Each morning, the patient answered
      questions on five sleep variables: sleep quality (SQ), sleep recreational value
      (SRV), total sleep time (TST), total wake time (TWT), and awakenings during sleep
      period (ADS). For the purpose of this study, the time series of the nighttime
      urinary neopterin levels and the five sleep variables were determined. Using
      centered moving average (CMA) smoothing and cross-correlational analysis, this
      study showed that increases in the positive sleep variables SQ and SRV were
      followed by urinary neopterin concentration decreases after 96-120 h (SQ, lag 4:
      r = -0.411; p = 0.044; SRV: lag 4: r = -0.472; p = 0.021) and 120-144 h (SRV, lag
      5: r = -0.464; p = 0.026). Increases in the negative sleep variable TWT, by
      contrast, were followed by increases in urinary neopterin concentrations 72-96 h
      later (lag 3: r = 0.522; p = 0.009). No systematic effects in the other
      direction, i.e., from urinary neopterin levels to sleep, were observed in this
      study. Although preliminary, the findings of this study highlight the benefit of
      carefully investigating temporal delays and directions of effects when studying
      the dynamic relationship between sleep and immune variables in the natural
      context of everyday life.

PMID- 29375464
TI  - A Meta-Analysis of Adenosine A2A Receptor Antagonists on Levodopa-Induced
      Dyskinesia In Vivo.
AB  - Background: Long-term use of levodopa (l-dopa) is inevitably complicated with
      highly disabling fluctuations and drug-induced dyskinesias, which pose major
      challenges to the existing drug therapy of Parkinson's disease. Methods: In this
      study, we conducted a systematic review and meta-analysis to assess the efficacy
      of A2A receptor antagonists on reducing l-dopa-induced dyskinesias (LID).
      Results: Nine studies with a total of 152 animals were included in this meta
      analysis. Total abnormal involuntary movements (AIM) score, locomotor activity,
      and motor disability were reported as outcome measures in 5, 5, and 3 studies,
      respectively. Combined standardized mean difference (SMD) estimates were
      calculated using a random-effects model. We pooled the whole data and found that,
      when compared to l-dopa alone, A2A receptor antagonists plus l-dopa treatment
      showed no effect on locomotor activity (SMD -0.00, 95% confidence interval (CI): 
      2.52 to 2.52, p = 1.0), superiority in improvement of motor disability (SMD 
      5.06, 95% CI: -9.25 to -0.87, p = 0.02) and more effective in control of AIM (SMD
      -1.82, 95% CI: -3.38 to -0.25, p = 0.02). Conclusion: To sum up, these results
      demonstrated that A2A receptor antagonists appear to have efficacy in animal
      models of LID. However, large randomized clinical trials testing the effects of
      A2A receptor antagonists in LID patients are always warranted.

PMID- 29375466
TI  - Magnetic Resonance Imaging-Based Prediction of the Relationship between Whiplash
      Injury and Temporomandibular Disorders.
AB  - Purpose: Whiplash injury can cause internal derangement of the temporomandibular
      joint (TMJ) and lead to temporomandibular disorders (TMDs). Our aim was to
      evaluate whether the initial clinical findings in TMD patients with whiplash
      injury are correlated with their magnetic resonance imaging (MRI)
      characteristics. Materials and methods: This case-control study involved 219
      patients (135 women, 84 men; mean age: 37.84 years) who visited our orofacial
      pain clinic with TMD; TMD was diagnosed using the diagnostic criteria for TMD
      Axis I. Patients were categorized into three groups based on the presence and
      type of macrotrauma: in the "wTMD" group, patients had suffered whiplash injury;
      patients in the "pTMD" group had post-traumatic TMD; the "iTMD" group comprised
      patients who had presented with TMD symptoms and had sustained no macrotrauma. We
      investigated the presence of disk displacement, effusion, disk deformity, and
      condylar degeneration, and changes in the lateral pterygoid muscle (LPM). To
      evaluate the severity of TMD pain and objectively analyze symptoms, we used a
      visual analog scale (VAS), palpation index (PI), neck PI, dysfunction index, and
      craniomandibular index (CMI). Results: The VAS scores, and the severity indexes
      of the TMD including PI, neck PI, and CMI were highest in the wTMD patients.
      Atrophy of the LPM was most commonly seen in the wTMD group, as was disk
      deformity. In wTMD patients only, VAS score was significantly correlated with
      stress; it was correlated with headache in wTMD and iTMD patients. The clinical
      symptoms of TMD were not correlated with MRI findings in the wTMD group. However,
      alterations in the LPM were strongly correlated with disk displacement.
      Conclusion: If clinicians recognize alterations in the LPM and disk displacement
      in the TMJ, they will better understand the clinical symptoms and pathophysiology
      of TMD with whiplash injury. Whiplash injury may lead to TMD via different
      mechanisms from other macrotraumas.

PMID- 29375467
TI  - Using Corticomuscular Coherence to Reflect Function Recovery of Paretic Upper
      Limb after Stroke: A Case Study.
AB  - Purpose: Motor deficits after stroke are supposed to arise from the reduced
      neural drive from the brain to muscles. This study aimed to demonstrate the
      feasibility of reflecting the motor function improvement after stroke with the
      measurement of corticomuscular coherence (CMC) in an individual subject. Method:
      A stroke patient was recruited to participate in an experiment before and after
      the function recovery of his paretic upper limb, respectively. An elbow flexion
      task with a constant muscle contraction level was involved in the experiment.
      Electromyography and electroencephalography signals were recorded simultaneously
      to estimate the CMC. The non-parameter statistical analysis was used to test the
      significance of CMC differences between the first and second times of
      experiments. Result: The strongest corticomuscular coupling emerged at the motor
      cortex contralateral to the contracting muscles for both the affected and
      unaffected limbs. The strength of the corticomuscular coupling between activities
      from the paretic limb muscles and the contralateral motor cortex for the second
      time of experiment increased significantly compared with that for the first time.
      However, the CMC of the unaffected limb had no significant changes between two
      times of experiments. Conclusion: The results demonstrated that the increased
      corticomuscular coupling strength resulted from the motor function restoration of
      the paretic limb. The measure of CMC can reflect the recovery of motor function
      after stroke by quantifying interactions between activities from the motor cortex
      and controlled muscles.

PMID- 29375468
TI  - Quality of Life Assessment in Multiple Sclerosis: Different Perception between
      Patients and Neurologists.
AB  - Background: In recent years, neurologists are noticing that evaluation of
      multiple sclerosis (MS) patients based on combining relapses, disability
      progression, and magnetic resonance imaging activity may be insufficient to
      adequately assess suboptimal responses to available therapy. Inclusion of quality
      of life (QoL) parameters may contribute to breach this gap. Objective: To
      evaluate agreement levels between doctor and patient perception of QoL in MS.
      Methods: A total of 700 MS patients and 300 neurologists were invited to
      participate in a cross-sectional study by answering an e-mail questionnaire. The
      survey collected information on demographical data and included the Short Form
      questionnaire (SF-36). After completing the questionnaire, patients were given a
      standard written description of each of the subdomains assessed by SF-36 and
      asked to identify which three were the most important determinants of their
      overall health-related QoL. Results: A total of 135 neurologists and 380 MS
      patients responded the survey. Study population mean age was 42.1 +/- 10.5 years,
      with 61% presenting relapsing-remitting MS. SF-36 results were physical function
      68.4 +/- 30, physical role limitation 56.8 +/- 41.7, vitality 47.6 +/- 21.4, pain
      71.2 +/- 26.1, social function 72.6 +/- 28.6, emotional role limitation 63.2 +/-
      39.8, mental health 60 +/- 14.1, and general health 55.8 +/- 22. Doctors
      considered physical function (75%) and physical role limitation (70%) as the most
      important QoL determinants in MS, followed by emotional role limitation (52%).
      Patients however, assigned significantly different levels of importance to
      physical function (58%), and physical role limitation (46%) and considered
      vitality (52%) more important than their physicians (p < 0.001). Important to
      note, the results of SF-36 questionnaire were highly correlated with the
      perception gap between patients and neurologists (r = 0.89; p = 0.0004).
      Conclusion: Concerns on QoL in MS are different for patients and physicians. It
      is essential to enhance communication in order to better understand actual
      patient needs.

PMID- 29375470
TI  - Editorial: Imaging in Acute Stroke-New Options and State of the Art.

PMID- 29375465
TI  - Application of Metabolomics in Alzheimer's Disease.
AB  - Progress toward the development of efficacious therapies for Alzheimer's disease
      (AD) is halted by a lack of understanding early underlying pathological
      mechanisms. Systems biology encompasses several techniques including genomics,
      epigenomics, transcriptomics, proteomics, and metabolomics. Metabolomics is the
      newest omics platform that offers great potential for the diagnosis and prognosis
      of neurodegenerative diseases as an individual's metabolome reflects alterations
      in genetic, transcript, and protein profiles and influences from the environment.
      Advancements in the field of metabolomics have demonstrated the complexity of
      dynamic changes associated with AD progression underscoring challenges with the
      development of efficacious therapeutic interventions. Defining systems-level
      alterations in AD could provide insights into disease mechanisms, reveal sex
      specific changes, advance the development of biomarker panels, and aid in
      monitoring therapeutic efficacy, which should advance individualized medicine.
      Since metabolic pathways are largely conserved between species, metabolomics
      could improve the translation of preclinical research conducted in animal models
      of AD into humans. A summary of recent developments in the application of
      metabolomics to advance the AD field is provided below.

PMID- 29375469
TI  - Dietary Iron Repletion following Early-Life Dietary Iron Deficiency Does Not
      Correct Regional Volumetric or Diffusion Tensor Changes in the Developing Pig
      Brain.
AB  - Background: Iron deficiency is the most common micronutrient deficiency worldwide
      and children are at an increased risk due to the rapid growth occurring during
      early life. The developing brain is highly dynamic, requires iron for proper
      function, and is thus vulnerable to inadequate iron supplies. Iron deficiency
      early in life results in altered myelination, neurotransmitter synthesis, neuron
      morphology, and later-life cognitive function. However, it remains unclear if
      dietary iron repletion after a period of iron deficiency can recover structural
      deficits in the brain. Method: Twenty-eight male pigs were provided either a
      control diet (CONT; n = 14; 23.5 mg Fe/L milk replacer) or an iron-deficient diet
      (ID; n = 14; 1.56 mg Fe/L milk replacer) for phase 1 of the study, from postnatal
      day (PND) 2 until 32. Twenty pigs (n = 10/diet from phase 1) were used in phase 2
      of the study from PND 33 to 61, all pigs were provided a common iron sufficient
      diet, regardless of their early-life dietary iron status. All pigs remaining in
      the study were subjected to magnetic resonance imaging (MRI) at PND 32 and again
      at PND 61 using structural imaging sequences and diffusion tensor imaging (DTI)
      to assess volumetric and microstructural brain development, respectively. Data
      were analyzed using a two-way ANOVA to assess the main and interactive effects of
      early-life iron status and time. Results: An interactive effect was observed for
      absolute whole brain volumes, in which whole brain volumes of ID pigs were
      smaller at PND 32 but were not different than CONT pigs at PND 61. Analysis of
      brain region volumes relative to total brain volume indicated interactive effects
      (i.e., diet * day) in the cerebellum, olfactory bulb, and putamen-globus
      pallidus. Main effects of early-life iron status, regardless of imaging time
      point, were noted for decreased relative volumes of the left hippocampus, right
      hippocampus, thalamus, and increased relative white matter volume in ID pigs
      compared with CONT pigs. DTI indicated interactive effects for fractional
      anisotropy (FA) in the whole brain, left cortex, and right cortex. Main effects
      of early-life iron status, regardless of imaging time point, were observed for
      decreased FA values in the caudate, cerebellum, and internal capsule in ID pigs
      compared with CONT pigs. All comparisons described above were significant at P <
      0.05. Conclusion: Results from this study indicate that dietary iron repletion is
      able to compensate for reduced absolute brain volumes early in life; however,
      microstructural changes and altered relative brain volumes persist despite iron
      repletion.

PMID- 29375471
TI  - Cerebral Ischemia Increases Small Ubiquitin-Like Modifier Conjugation within
      Human Penumbral Tissue: Radiological-Pathological Correlation.
AB  - Posttranslational modification by small ubiquitin-like modifier (SUMO) regulates
      myriad physiological processes within cells and has been demonstrated to be
      highly activated in murine brains after cerebral ischemia. Numerous in vitro and
      murine in vivo studies have demonstrated that this increased SUMO conjugation is
      an endogenous neuroprotective stress response that has potential in being
      leveraged to develop novel therapies for ischemic stroke. However, SUMO
      activation has not yet been studied in poststroke human brains, presenting a
      clear limitation in translating experimental successes in murine models to human
      patients. Accordingly, here, we present a case wherein the brain tissue of a
      stroke patient (procured shortly after death) was processed by multiplex
      immunohistochemistry to investigate SUMO activation.

PMID- 29375472
TI  - Dietary Patterns and Fractures Risk in the Elderly.
AB  - Purpose: Although the role of dietary factors in the prevention of bone loss and
      fractures has been investigated in many studies, few studies have examined the
      association between dietary patterns and total body bone density. Our aim was to
      determine the relations between dietary patterns and whole-body bone mineral
      density (WB-BMD) and the association between dietary patterns, fractures, and
      multiple fractures in the elderly. Methods: This cross-sectional study included
      177 individuals aged >=65 years. A dual X-ray absorptiometry scan was performed
      to measure BMD. Dietary patterns were ascertained by a combination of dietary
      intake assessment and principal components analysis. Results: Only three dietary
      patterns correlated with whole-body bone density. The multivariate-adjusted mean
      bone density across tertiles of these dietary patterns showed that the highest
      tertile of both the patterns 1 and 2 had a significantly higher bone density than
      the lowest tertile (pattern 1: 1.021 +/- 0.01 and 1.070 +/- 0.01 g/cm2 for T1 and
      T3, respectively; p = 0.043; pattern 2: 1.023 +/- 0.01, and 1.081 +/- 0.01 g/cm2
      for T1 and T3, respectively; p = 0.003). We also find significant gender
      difference in these results. The highest adherence to the dietary pattern 5 was
      associated with decreased odds of having fractures (OR = 0.20, p = 0.009), and
      adherence to the pattern 1 was negatively associated with multiple fractures.
      Conclusion: A high adherence to the dietary pattern 1 (high intake of grains,
      fish and olive oil) was associated with a high BMD and a low number of fractures.
      The highest adherence to the dietary pattern 5 (legumes and wine) was associated
      with decreased odds of having fractures. Our finding would suggest a potential
      bone-preserving properties of specific dietary patterns in the elderly.

PMID- 29375473
TI  - Eel Kisspeptins: Identification, Functional Activity, and Inhibition on both
      Pituitary LH and GnRH Receptor Expression.
AB  - The European eel (Anguilla anguilla) presents a blockade of sexual maturation at
      a prepubertal stage due to a deficient production of gonadotropins. We previously
      initiated, in the eel, the investigation of the kisspeptin system, one of the
      major gatekeepers of puberty in mammals, and we predicted the sequence of two
      Kiss genes. In the present study, we cloned and sequenced Kiss1 and Kiss2 cDNAs
      from the eel brain. The tissue distributions of Kiss1 and Kiss2 transcripts, as
      investigated by quantitative real-time PCR, showed that both genes are primarily
      expressed in the eel brain and pituitary. The two 10-residue long sequences
      characteristic of kisspeptin, eel Kp1(10) and Kp2(10), as well as two longer
      sequences, predicted as mature peptides, eel Kp1(15) and Kp2(12), were
      synthesized and functionally analyzed. Using rat Kiss1 receptor-transfected
      Chinese hamster ovary cells, we found that the four synthesized eel peptides were
      able to induce [Ca2+]i responses, indicating their ability to bind mammalian
      KissR-1 and to activate second messenger pathways. In primary culture of eel
      pituitary cells, all four peptides were able to specifically and dose-dependently
      inhibit lhbeta expression, without any effect on fshbeta, confirming our previous
      data with heterologous kisspeptins. Furthermore, in this eel in vitro system, all
      four peptides inhibited the expression of the type 2 GnRH receptor (gnrh-r2). Our
      data revealed a dual inhibitory effect of homologous kisspeptins on both
      pituitary lhbeta and gnrh-r2 expression in the European eel.

PMID- 29375474
TI  - Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal
      Diagnosis and Treatment.
AB  - In thyroid health, the pituitary hormone thyroid-stimulating hormone (TSH) raises
      glandular thyroid hormone production to a physiological level and enhances
      formation and conversion of T4 to the biologically more active T3.
      Overstimulation is limited by negative feedback control. In equilibrium defining
      the euthyroid state, the relationship between TSH and FT4 expresses clusters of
      genetically determined, interlocked TSH-FT4 pairs, which invalidates their
      statistical correlation within the euthyroid range. Appropriate reactions to
      internal or external challenges are defined by unique solutions and homeostatic
      equilibria. Permissible variations in an individual are much more closely
      constrained than over a population. Current diagnostic definitions of subclinical
      thyroid dysfunction are laboratory based, and do not concur with treatment
      recommendations. An appropriate TSH level is a homeostatic concept that cannot be
      reduced to a fixed range consideration. The control mode may shift from feedback
      to tracking where TSH becomes positively, rather than inversely related with FT4.
      This is obvious in pituitary disease and severe non-thyroid illness, but extends
      to other prevalent conditions including aging, obesity, and levothyroxine (LT4)
      treatment. Treatment targets must both be individualized and respect altered
      equilibria on LT4. To avoid amalgamation bias, clinically meaningful
      stratification is required in epidemiological studies. In conclusion, pituitary
      TSH cannot be readily interpreted as a sensitive mirror image of thyroid function
      because the negative TSH-FT4 correlation is frequently broken, even inverted, by
      common conditions. The interrelationships between TSH and thyroid hormones and
      the interlocking elements of the control system are individual, dynamic, and
      adaptive. This demands a paradigm shift of its diagnostic use.

PMID- 29375475
TI  - Interactions between Genetics and Sugar-Sweetened Beverage Consumption on Health
      Outcomes: A Review of Gene-Diet Interaction Studies.
AB  - The consumption of sugar-sweetened beverages (SSB), which includes soft drinks,
      fruit drinks, and other energy drinks, is associated with excess energy intake
      and increased risk for chronic metabolic disease among children and adults. Thus,
      reducing SSB consumption is an important strategy to prevent the onset of chronic
      diseases, and achieve and maintain a healthy body weight. The mechanisms by which
      excessive SSB consumption may contribute to complex chronic diseases may
      partially depend on an individual's genetic predisposition. Gene-SSB interaction
      investigations, either limited to single genetic loci or including multiple
      genetic variants, aim to use genomic information to define mechanistic pathways
      linking added sugar consumption from SSBs to those complex diseases. The purpose
      of this review is to summarize the available gene-SSB interaction studies
      investigating the relationships between genetics, SSB consumption, and various
      health outcomes. Current evidence suggests there are genetic predispositions for
      an association between SSB intake and adiposity; evidence for a genetic
      predisposition between SSB and type 2 diabetes or cardiovascular disease is
      limited.

PMID- 29375477
TI  - Open-Label, Randomized, Two-Way, Crossover Study Assessing the Bioequivalence of
      the Liquid Formulation versus the Freeze-Dried Formulation of Recombinant Human
      FSH and Recombinant Human LH in a Fixed 2:1 Combination (Pergoveris(r)) in
      Pituitary-Suppressed Healthy Women.
AB  - This was a Phase I, open-label, randomized, two-period, two-sequence crossover
      study [ClinicalTrials.gov NCT02317809
      (https://www.clinicaltrials.gov/ct2/show/NCT02317809); EudraCT 2014-003506-32]
      assessing the bioequivalence of the liquid and freeze-dried formulations of fixed
      dose, fixed-ratio (2:1) combination recombinant human follicle-stimulating
      hormone plus recombinant human luteinizing hormone (r-hFSH/r-hLH). The safety and
      tolerability of the two formulations were also assessed. Healthy premenopausal
      women were randomized to one of two crossover dosing schedules. Subjects in
      Treatment Sequence 1 received a single subcutaneous dose (900/450 IU r-hFSH/r
      hLH) of the liquid formulation of r-hFSH/r-hLH on Day 1 of Dose Period 1 and,
      after a washout period of at least 14 days, a single subcutaneous dose (900/450
      IU r-hFSH/r-hLH) of the freeze-dried formulation of r-hFSH/r-hLH (reconstituted
      in water for injection prior to administration) on Day 1 of Dose Period 2.
      Subjects in Treatment Sequence 2 received the treatments in reverse order. The
      primary endpoints were AUC0-t (area under the serum concentration-time curve from
      time 0 to the time of the last quantifiable concentration) and Cmax (maximum
      serum concentration) for FSH and LH, both baseline corrected. A total of 34
      subjects were randomized, and 22 subjects were included in the bioequivalence
      evaluation. Overall, the mean observed PK profiles and individual PK parameters
      were comparable for the liquid and freeze-dried formulations, although a median
      difference in the tmax (time to reach maximum observed concentration) of FSH of
      ~4.5 h was observed between the formulations. The calculated 90% confidence
      intervals of the mean liquid formulation/freeze-dried formulation ratios for Cmax
      and AUC0-t were within the bioequivalence range (80-125%) for both LH and FSH,
      confirming bioequivalence between the two formulations. The safety and
      tolerability profiles of the two formulations were similar. The liquid
      formulation can, therefore, be expected to provide the same efficacy as the
      freeze-dried formulation, with no differences in tolerability.

PMID- 29375476
TI  - Alterations in Metabolism and Diurnal Rhythms following Bilateral Surgical
      Removal of the Superior Cervical Ganglia in Rats.
AB  - Mammalian circadian rhythms are controlled by a master pacemaker located in the
      suprachiasmatic nuclei (SCN), which is synchronized to the environment by photic
      and nonphotic stimuli. One of the main functions of the SCN is to regulate
      peripheral oscillators to set temporal variations in the homeostatic control of
      physiology and metabolism. In this sense, the SCN coordinate the activity/rest
      and feeding/fasting rhythms setting the timing of food intake, energy
      expenditure, thermogenesis, and active and basal metabolism. One of the major
      time cues to the periphery is the nocturnal melatonin, which is synthesized and
      secreted by the pineal gland. Under SCN control, arylalkylamine N
      acetyltransferase (AA-NAT)-the main enzyme regulating melatonin synthesis in
      vertebrates-is activated at night by sympathetic innervation that includes the
      superior cervical ganglia (SCG). Bilateral surgical removal of the superior
      cervical ganglia (SCGx) is considered a reliable procedure to completely prevent
      the nocturnal AA-NAT activation, irreversibly suppressing melatonin rhythmicity.
      In the present work, we studied the effects of SCGx on rat metabolic parameters
      and diurnal rhythms of feeding and locomotor activity. We found a significant
      difference between SCGx and sham-operated rats in metabolic variables such as an
      increased body weight/food intake ratio, increased adipose tissue, and decreased
      glycemia with a normal glucose tolerance. An analysis of locomotor activity and
      feeding rhythms showed an increased daytime (lights on) activity (including food
      consumption) in the SCGx group. These alterations suggest that superior cervical
      ganglia-related feedback mechanisms play a role in SCN-periphery phase
      coordination and that SCGx is a valid model without brain-invasive surgery to
      explore how sympathetic innervation affects daily (24 h) patterns of activity,
      food consumption and, ultimately, its role in metabolism homeostasis.

PMID- 29375478
TI  - Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human
      White Adipocyte Model.
AB  - Background and aims: Gut-derived short-chain fatty acids (SCFA), formed by
      microbial fermentation of dietary fibers, are believed to be involved in the
      etiology of obesity and diabetes. Previous data from our group showed that
      colonic infusions of physiologically relevant SCFA mixtures attenuated whole-body
      lipolysis in overweight men. To further study potential mechanisms involved in
      the antilipolytic properties of SCFA, we aimed to investigate the in vitro
      effects of SCFA incubations on intracellular lipolysis and signaling using a
      human white adipocyte model, the human multipotent adipose tissue-derived stem
      (hMADS) cells. Methods: hMADS adipocytes were incubated with mixtures of acetate,
      propionate, and butyrate or single SCFA (acetate, propionate and butyrate) in
      concentrations ranging between 1 umol/L and 1 mmol/L. Glycerol release and lipase
      activation was investigated during basal conditions and following beta-adrenergic
      stimulation. Results: SCFA mixtures high in acetate and propionate decreased
      basal glycerol release, when compared to control (P < 0.05), while mixtures high
      in butyrate had no effect. Also, beta-adrenergic receptor mediated glycerol
      release was not significantly altered following incubation with SCFA mixtures.
      Incubation with only acetate decreased basal (1 umol/L) and beta-adrenergically
      (1 umol/L and 1 mmol/L) mediated glycerol release when compared with control (P <
      0.05). In contrast, butyrate (1 umol/L) slightly increased basal and beta
      adrenergically mediated glycerol release compared with control (P < 0.05), while
      propionate had no effect on lipolysis. The antilipolytic effect of acetate was
      accompanied by a reduced phosphorylation of hormone-sensitive lipase (HSL) at
      serine residue 650. In addition, inhibition of Gi G proteins following pertussis
      toxin treatment prevented the antilipolytic effect of acetate. Conclusion: The
      present data demonstrated that acetate was mainly responsible for the
      antilipolytic effects of SCFA and acts via attenuation of HSL phosphorylation in
      a Gi-coupled manner in hMADS adipocytes. Therefore, the modulation of colonic and
      circulating acetate may be an important target to modulate human adipose tissue
      lipid metabolism.

PMID- 29375479
TI  - Short Stature Diagnosis and Referral.
AB  - The "360 degrees  GH in Europe" meeting, which examined various aspects of GH
      diseases, was held in Lisbon, Portugal, in June 2016. The Merck KGaA (Germany)
      funded meeting comprised three sessions entitled "Short Stature Diagnosis and
      Referral," "Optimizing Patient Management," and "Managing Transition." Each
      session had three speaker presentations, followed by a discussion period, and is
      reported as a manuscript, authored by the speakers. The first session examined
      current processes of diagnosis and referral by endocrine specialists for
      pediatric patients with short stature. Requirements for referral vary widely, by
      country and by patient characteristics such as age. A balance must be made to
      ensure eligible patients get referred while healthcare systems are not over
      burdened by excessive referrals. Late referral and diagnosis of non-GH deficiency
      conditions can result in increased morbidity and mortality. The consequent delays
      in making a diagnosis may compromise the effectiveness of GH treatment.
      Algorithms for growth monitoring and evaluation of skeletal disproportions can
      improve identification of non-GH deficiency conditions. Performance and
      validation of guidelines for diagnosis of GH deficiency have not been
      sufficiently tested. Provocative tests for investigation of GH deficiency remain
      equivocal, with insufficient information on variations due to patient
      characteristics, and cutoff values for definition differ not only by country but
      also by the assay used. When referring and diagnosing causes of short stature in
      pediatric patients, clinicians need to rely on many factors, but the most
      essential is clinical experience.

PMID- 29375480
TI  - Multiple Salivary Cortisol Measurements Are a Useful Tool to Optimize Metyrapone
      Treatment in Patients with Cushing's Syndromes Treatment: Case Presentations.
AB  - Measuring salivary cortisol is both convenient and non-invasive for patients;
      however, its usefulness as a marker for monitoring medical therapy has not yet
      been established. The aim of this study was to assess the utility of multiple
      salivary cortisol measurements in patients with Cushing's syndrome (CS) during
      medical therapy. Six patients with CS (three with cortisol-secreting
      adrenocortical adenoma and three with ACTH-secreting pituitary adenoma) were
      recruited. Samples for morning serum cortisol, urinary free cortisol (UFC), and
      multiple salivary cortisol levels were collected before and during metyrapone
      treatment. The area under the curve (AUC) and mean value (MV) of daily salivary
      cortisol levels were calculated. In five out of six patients, UFC were
      normalized; however, multiple salivary cortisol measurements revealed an impaired
      diurnal cortisol rhythm in these patients. To verify the usefulness of multiple
      salivary cortisol measurements, we performed a prospective case study of a
      patient in whom the excess secretion of cortisol was not controlled (UFC 211
      MUg/day) with 2,250 mg/day in four divided doses of metyrapone. Multiple
      measurements of salivary cortisol revealed that cortisol levels elevated before
      the next administration. Accordingly, we shortened the interval by increasing the
      number of administration from four to five times per day, with a slight increment
      of daily dose of 2,500 mg. These optimizations resulted in a drastic improvement
      of diurnal pattern as well as UFC level (101 MUg/day). Changes in both the MV and
      AUC of salivary cortisol levels were more correlated with those in UFC levels
      (Correlation coefficient 0.75, p = 0.007, and 0.70, p = 0.017) than those in the
      morning serum cortisol levels (0.42, p = 0.200), indicating that multiple
      salivary cortisol measurements reflect more precisely the excess secretion of
      cortisol. Our preliminary data suggest that multiple salivary cortisol
      measurements can be a useful tool to visualize the diurnal cortisol rhythm and to
      determine the dose and timing of metyrapone during the treatment in patients with
      CS.

PMID- 29375481
TI  - Hallmarks of Human Small Antral Follicle Development: Implications for Regulation
      of Ovarian Steroidogenesis and Selection of the Dominant Follicle.
AB  - Regulation of human ovarian steroidogenesis differs from other species and
      precise knowledge on how human small antral follicles (hSAF) develop and acquire
      competence for continued growth and steroid output is still incomplete. The
      present study has characterized almost 1,000 normal hSAF collected in connection
      with cryopreservation of ovarian tissue for fertility preservation. The antral
      follicles (ranging from 3 to 13 mm) were generally aspirated from one ovary
      surgically removed during the natural cycle, and the follicular fluid (FF) and
      the granulosa cells (GC) were isolated and snap-frozen. In FF, the following
      hormones were measured: inhibin-B, inhibin-A, AMH, follistatin, PAPP-A,
      estradiol, progesterone, testosterone, and androstenedione. In GC, mRNA gene
      expressions using q-PCR were measured for the following genes: FSHR, AMH, CYP19,
      and AR. All samples in which one of the abovementioned parameters was measured
      were included, but typically multiple parameters were measured. Highly
      significant differences in concentration and follicular content in relation to
      follicular diameter were found for all measured hormones despite massive
      variability in-between follicles for any given diameter. The results demonstrate
      that profound changes take place in the hormonal microenvironment around
      follicular diameters of 8-11 mm corresponding to when follicular selection
      occurs. At this point, inhibin-B and inhibin-A showed distinct peaks concomitant
      with a significant reduction in both AMH protein and mRNA expression.
      Concentrations of inhibins, androgens, FSHR, and AR were intimately associated,
      and it is suggested that inhibin-B in combination with PAPP-A and thereby IGF2
      activity exerts important paracrine signaling at follicular selection. At the
      same time upregulation of estradiol synthesis and CYP19 mRNA expression increased
      steroid output profoundly. Furthermore, the highly significant association
      between FSHR and AR mRNA gene expression enforces important functions of
      androgens in follicular development. Collectively, these data reintroduce the
      understanding of the follicular phase as two parted in which regulation of
      steroidogenesis differs. The profound changes taking place around follicular
      selection highlight important paracrine actions of TGF-beta family members and
      IGFs for securing dominance of the selected follicle.

PMID- 29375483
TI  - Variations of the Organic Matter Composition in the Sea Surface Microlayer: A
      Comparison between Open Ocean, Coastal, and Upwelling Sites Off the Peruvian
      Coast.
AB  - The sea surface microlayer (SML) is the thin boundary layer between the ocean and
      the atmosphere, making it important for air-sea exchange processes. However,
      little is known about what controls organic matter composition in the SML. In
      particular, there are only few studies available on the differences of the SML of
      various oceanic systems. Here, we compared the organic matter and neuston species
      composition in the SML and the underlying water (ULW) at 11 stations with varying
      distance from the coast in the Peruvian upwelling regime, a system with high
      emissions of climate relevant trace gases, such as N2O and CO2. In the open
      ocean, organic carbon, and amino acids were highly enriched in the SML compared
      to the ULW. The enrichment decreased at the coastal stations and vanished in the
      upwelling regime. At the same time, the degradation of organic matter increased
      from the open ocean to the upwelling stations. This suggests that in the open
      ocean, upward transport processes or new production of organic matter within the
      SML are faster than degradation processes. Phytoplankton was generally not
      enriched in the SML, one group though, the Trichodesmium-like TrL (possibly
      containing Trichodesmium), were enriched in the open ocean but not in the
      upwelling region indicating that they find a favorable habitat in the open ocean
      SML. Our data show that the SML is a distinct habitat; its composition is more
      similar among different systems than between SML and ULW of a single station.
      Generally the enrichment of organic matter is assumed to be reduced when
      encountering low primary production and high wind speeds. However, our study
      shows the highest enrichments of organic matter in the open ocean which had the
      lowest primary production and the highest wind speeds.

PMID- 29375482
TI  - Dual Actions of Mammalian and Piscine Gonadotropin-Inhibitory Hormones, RFamide
      Related Peptides and LPXRFamide Peptides, in the Hypothalamic-Pituitary-Gonadal
      Axis.
AB  - Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that
      decreases gonadotropin synthesis and release by directly acting on the
      gonadotrope or by decreasing the activity of gonadotropin-releasing hormone
      (GnRH) neurons. GnIH is also called RFamide-related peptide in mammals or
      LPXRFamide peptide in fishes due to its characteristic C-terminal structure. The
      primary receptor for GnIH is GPR147 that inhibits cAMP production in target
      cells. Although most of the studies in mammals, birds, and fish have shown the
      inhibitory action of GnIH in the hypothalamic-pituitary-gonadal (HPG) axis,
      several in vivo studies in mammals and many in vivo and in vitro studies in fish
      have shown its stimulatory action. In mouse, although the firing rate of the
      majority of GnRH neurons is decreased, a small population of GnRH neurons is
      stimulated by GnIH. In hamsters, GnIH inhibits luteinizing hormone (LH) release
      in the breeding season when their endogenous LH level is high but stimulates LH
      release in non-breeding season when their LH level is basal. Besides different
      effects of GnIH on the HPG axis depending on the reproductive stages in fish,
      higher concentration or longer duration of GnIH administration can stimulate
      their HPG axis. These results suggest that GnIH action in the HPG axis is
      modulated by sex-steroid concentration, the action of neuroestrogen synthesized
      by the activity of aromatase stimulated by GnIH, estrogen membrane receptor,
      heteromerization and internalization of GnIH, GnRH, and estrogen membrane
      receptors. The inhibitory and stimulatory action of GnIH in the HPG axis may have
      a physiological role to maintain reproductive homeostasis according to
      developmental and reproductive stages.

PMID- 29375484
TI  - Exogenous Nitrogen Addition Reduced the Temperature Sensitivity of Microbial
      Respiration without Altering the Microbial Community Composition.
AB  - Atmospheric nitrogen (N) deposition is changing in both load quantity and
      chemical composition. The load effects have been studied extensively, whereas the
      composition effects remain poorly understood. We conducted a microcosm experiment
      to study how N chemistry affected the soil microbial community composition
      characterized by phospholipid fatty acids (PLFAs) and activity indicated by
      microbial CO2 release. Surface and subsurface soils collected from an old-growth
      subtropical forest were supplemented with three N-containing materials (ammonium,
      nitrate, and urea) at the current regional deposition load (50 kg ha-1 yr-1) and
      incubated at three temperatures (10, 20, and 30 degrees C) to detect the
      interactive effects of N deposition and temperature. The results showed that the
      additions of N, regardless of form, did not alter the microbial PLFAs at any of
      the three temperatures. However, the addition of urea significantly stimulated
      soil CO2 release in the early incubation stage. Compared with the control, N
      addition consistently reduced the temperature dependency of microbial
      respiration, implying that N deposition could potentially weaken the positive
      feedback of the warming-stimulated soil CO2 release to the atmosphere. The
      consistent N effects for the surface and subsurface soils suggest that the
      effects of N on soil microbial communities may be independent of soil chemical
      contents and stoichiometry.

PMID- 29375485
TI  - EPSP of L. casei BL23 Protected against the Infection Caused by Aeromonas veronii
      via Enhancement of Immune Response in Zebrafish.
AB  - Aquaculture is the fastest-growing food production sector in the world, and it
      supplies nearly 50% of the global food fish supply. However, disease outbreaks
      have become a major problem in the fish farming industry. The beneficial
      contribution of probiotic bacteria to aquatic animals' health has been widely
      described, and they have been widely used in aquaculture for disease control and
      growth promotion. However, the action of probiotic bacterial components and
      mechanisms underlying protection against pathogens afforded by probiotic bacteria
      remain poorly understood. In the present study, we pre-colonized zebrafish larvae
      (before hatching) with 17 potential probiotic bacterial strains and screened for
      those possessing anti-infective effects against Aeromonas veronii. We found that
      Lactobacillus casei BL23 significantly increased the survival of zebrafish larvae
      upon A. veronii infection. Using a germ-free (GF) zebrafish model and gut
      microbiota transplant experiment, we showed that L. casei BL23 per se has anti
      infective effects in zebrafish larvae, which does not involve microbiota.
      Furthermore, we identified an exopolysaccharide-protein complex (EPSP) extracted
      from L. casei BL23 cells, which consisted of a 40-45 KD size protein and an
      exopolysaccharide composed of alpha-Rha, alpha-Glc, beta-GlcNAc, and beta-GalNAc.
      EPSP significantly increased the survival rate of GF zebrafish at a dose of 10-20
      MUg/ml after A. veronii infection (P < 0.01). In addition, the EPSP induced a
      higher expression of TLR1 and TLR2, and modulated the expression profile of pro
      inflammatory and anti-inflammatory cytokines in zebrafish liver (ZFL) cells. Our
      data indicated that the anti-infective effect of EPSP from L. casei BL23 was
      mediated by enhancement of immune responses in zebrafish, which might involve the
      TLR1/TLR2 signal pathway.

PMID- 29375486
TI  - Combination Strategies to Enhance the Efficacy of Antimicrobial Peptides against
      Bacterial Biofilms.
AB  - The great clinical significance of biofilm-associated infections and their
      inherent recalcitrance to antibiotic treatment urgently demand the development of
      novel antibiofilm strategies. In this regard, antimicrobial peptides (AMPs) are
      increasingly recognized as a promising template for the development of
      antibiofilm drugs. Indeed, owing to their main mechanism of action, which relies
      on the permeabilization of bacterial membranes, AMPs exhibit a strong
      antimicrobial activity also against multidrug-resistant bacteria and slow-growing
      or dormant biofilm-forming cells and are less prone to induce resistance compared
      to current antibiotics. Furthermore, the antimicrobial potency of AMPs can be
      highly increased by combining them with conventional (antibiotics) as well as
      unconventional bioactive molecules. Combination treatments appear particularly
      attractive in the case of biofilms since the heterogeneous nature of these
      microbial communities requires to target cells in different metabolic states
      (e.g., actively growing cells, dormant cells) and environmental conditions (e.g.,
      acidic pH, lack of oxygen or nutrients). Therefore, the combination of different
      bioactive molecules acting against distinct biofilm components has the potential
      to facilitate biofilm control and/or eradication. The aim of this review is to
      highlight the most promising combination strategies developed so far to enhance
      the therapeutic potential of AMPs against bacterial biofilms. The rationale
      behind and beneficial outcomes of using AMPs in combination with conventional
      antibiotics, compounds capable of disaggregating the extracellular matrix,
      inhibitors of signaling pathways involved in biofilm formation (i.e., quorum
      sensing), and other peptide-based molecules will be presented and discussed.

PMID- 29375487
TI  - Characterization of Antimicrobial-Producing Beneficial Bacteria Isolated from
      Huanglongbing Escape Citrus Trees.
AB  - The microbiome associated with crop plants has a strong impact on their health
      and productivity. Candidatus Liberibacter asiaticus (Las), the bacterial pathogen
      responsible for Huanglongbing (HLB) disease, lives inside the phloem of citrus
      plants including the root system. It has been suggested that Las negatively
      affects citrus microbiome. On the other hand, members of citrus microbiome also
      influence the interaction between Las and citrus. Here, we report the isolation
      and characterization of multiple putative beneficial bacteria from healthy citrus
      rhizosphere. Firstly, six bacterial strains showing antibacterial activity
      against two bacteria closely related to Las: Agrobacterium tumefaciens and
      Sinorhizobium meliloti were selected. Among them, Burkholderia metallica strain
      A53 and Burkholderia territorii strain A63 are within the beta-proteobacteria
      class, whereas Pseudomonas granadensis strain 100 and Pseudomonas geniculata
      strain 95 are within the gamma-proteobacteria class. Additionally, two gram
      positive bacteria Rhodococcus jialingiae strain 108 and Bacillus pumilus strain
      104 were also identified. Secondly, antimicrobial activity against three fungal
      pathogens: Alternaria alternata, Colletotrichum acutatum, Phyllosticta
      citricarpa, and two oomycetes: Phytophthora nicotianae and Phytophthora
      palmivora. Four bacterial strains Burkholderia territorii A63, Burkholderia
      metallica A53, Pseudomonas geniculata 95, and Bacillus pumilus 104 were shown to
      have antagonistic activity against the citrus root pathogen Phytophthora
      nicotianae based on dual culture antagonist assays and compartmentalized petri
      dish assays. The four selected bacteria were sequenced. Genes involved in
      phosphate solubilization, siderophore production and iron acquisition, volatile
      organic compound production, osmoprotection and osmotic tolerance, phytohormone
      production, antagonism, and nutrient competition were predicted and discussed
      related to the beneficial traits.

PMID- 29375489
TI  - Editorial: Eukaryotic Microbes Store Nitrate for "Breathing" in Anoxia.

PMID- 29375488
TI  - Identification and Characterization of 5' Untranslated Regions (5'UTRs) in
      Zymomonas mobilis as Regulatory Biological Parts.
AB  - Regulatory RNA regions within a transcript, particularly in the 5' untranslated
      region (5'UTR), have been shown in a variety of organisms to control the
      expression levels of these mRNAs in response to various metabolites or
      environmental conditions. Considering the unique tolerance of Zymomonas mobilis
      to ethanol and the growing interest in engineering microbial strains with
      enhanced tolerance to industrial inhibitors, we searched natural cis-regulatory
      regions in this microorganism using transcriptomic data and bioinformatics
      analysis. Potential regulatory 5'UTRs were identified and filtered based on
      length, gene function, relative gene counts, and conservation in other organisms.
      An in vivo fluorescence-based screening system was developed to confirm the
      responsiveness of 36 5'UTR candidates to ethanol, acetate, and xylose stresses.
      UTR_ZMO0347 (5'UTR of gene ZMO0347 encoding the RNA binding protein Hfq) was
      found to down-regulate downstream gene expression under ethanol stress. Genomic
      deletion of UTR_ZMO0347 led to a general decrease of hfq expression at the
      transcript level and increased sensitivity for observed changes in Hfq expression
      at the protein level. The role of UTR_ZMO0347 and other 5'UTRs gives us insight
      into the regulatory network of Z. mobilis in response to stress and unlocks new
      strategies for engineering robust industrial strains as well as for harvesting
      novel responsive regulatory biological parts for controllable gene expression
      platforms in this organism.

PMID- 29375490
TI  - The Negative Effects of KPN00353 on Glycerol Kinase and Microaerobic 1,3
      Propanediol Production in Klebsiella pneumoniae.
AB  - 1,3-Propanediol (1,3-PD) is a valuable chemical intermediate in the synthesis of
      polyesters, polyethers, and polyurethanes, which have applications in various
      products such as cloth, bottles, films, tarpaulins, canoes, foam seals, high
      resilience foam seating, and surface coatings. Klebsiella pneumoniae can produce
      1,3-PD from glycerol. In this study, KPN00353, an EIIA homologue in the
      phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS), was found
      to play a negative regulatory role in 1,3-PD production under microaerobic
      conditions via binding to glycerol kinase (GlpK). The primary sequence of
      KPN00353 is similar to those of the fructose-mannitol EIIA (EIIFru and EIIAMtl)
      family. The interaction between KPN00353 and GlpK resulted in inhibition of the
      synthesis of glycerol-3-phosphate (G3P) and correlated with reductions in
      glycerol uptake and the production of 1,3-PD. Based on structure modeling, we
      conclude that residue H65 of KPN00353 plays an important role in the interaction
      with GlpK. We mutated this histidine residue to aspartate, glutamate, arginine
      and glutamine to assess the effects of each KPN00353 variant on the interaction
      with GlpK, on the synthesis of G3P and on the production of 1,3-PD. Our results
      illuminate the role of KPN00353 in 1,3-PD production by K. pneumoniae under
      microaerobic conditions.

PMID- 29375491
TI  - The P-Type ATPase PA1429 Regulates Quorum-Sensing Systems and Bacterial
      Virulence.
AB  - Pseudomonas aeruginosa is becoming an increasingly prevalent pathogen, capable of
      causing numerous life threatening infections in immunocompromised patients. The
      three hierarchically arranged quorum sensing (QS) systems, namely las, rhl, and
      pqs play key roles in coordinating virulence expression in P. aeruginosa.
      However, the regulatory mechanisms of the pqs system have not been fully
      elucidated. To identify new genes involved in synthesis of the Pseudomonas
      quinolone signal (PQS), a transposon mutagenesis library was constructed. PA1429
      was found to inhibit PQS biosynthesis. The PA1429 deletion mutant also exhibited
      increased bacterial motility, biofilm formation, and virulence in a mouse model
      of acute lung infection. Interestingly, it also displayed reduced tolerance to
      oxidative stress. Mutated pqsH in the PA1429 deletion background restored
      bacterial susceptibility to H2O2. In addition, our data showed that PA1429
      repressed the expression of las and rhl systems. Overall, these results provide
      new insights into the complex regulatory networks of quorum-sensing and virulence
      expression in P. aeruginosa.

PMID- 29375492
TI  - Characterization of Pathogenic Vibrio parahaemolyticus from the Chesapeake Bay,
      Maryland.
AB  - Vibrio parahaemolyticus is the leading cause of bacterial gastroenteritis
      associated with seafood consumption in the United States. Here we investigated
      the presence of virulence factors and genetic diversity of V. parahaemolyticus
      isolated from water, oyster, and sediment samples from the Chesapeake Bay,
      Maryland. Of more than 2,350 presumptive Vibrio collected, more than half were
      confirmed through PCR as V. parahaemolyticus, with 10 encoding both tdh and trh
      and 6 encoding only trh. Potentially pathogenic V. parahaemolyticus were then
      serotyped with O1:KUT and O3:KUT predominant. Furthermore, pulsed-field gel
      electrophoresis was performed and the constructed dendrogram displayed high
      diversity, as did results from multiple-locus VNTR analysis. Vibrio
      parahaemolyticus was readily isolated from Chesapeake Bay waters but was less
      frequently isolated from oyster and sediment samples collected during this study.
      Potentially pathogenic V. parahaemolyticus was isolated in fewer numbers and the
      isolates displayed expansive diversity. Although characteristics of the
      pathogenic V. parahaemolyticus were highly variable and the percent of pathogenic
      V. parahaemolyticus detected was low, it is important to note that, pathogenic V.
      parahaemolyticus are present in the Chesapeake Bay, warranting seafood monitoring
      to minimize risk of disease for the public, and to reduce the economic burden of
      V. parahaemolyticus related illness.

PMID- 29375493
TI  - The Effect of Seed-Borne Fungi and Epichloe Endophyte on Seed Germination and
      Biomass of Elymus sibiricus.
AB  - The interactive effects of asexual Epichloe (formerly known as Neotyphodium)
      endophytes isolated from Hordeum brevisubulatum, Elymus tangutorum and
      Achnatherum inebrians, and seed-borne fungi on Elymus sibiricus seeds, were
      determined by an in vitro study using supernatants from liquid cultures of the
      endophyte strains. In an 8 week greenhouse study, the effects on the seedlings
      growth was measured. The in vitro study was carried out with the seed-borne fungi
      Alternaria alternata, Bipolaris sorokiniana, Fusarium avenaceum, and a Fusarium
      sp. isolated from E. sibiricus. Different concentrations and combinations of the
      liquid cultures of endophytic fungi enhanced the interim germination, germination
      rate, length of coleoptile and radicle, and seedling dry weight of E. sibiricus
      under stress from seed-borne fungi. In the greenhouse study, different
      concentrations of the supernatant of the endophytes from H. brevisubulatum and E.
      tangutorum but not A. inebrians, signficantly (P < 0.05) enhanced E. sibiricus
      seed germination. There was no significant (P > 0.05) increase of the tiller
      numbers after 2 weeks. However, later on, there were significant (P < 0.05)
      increases in tiller number (4-8 weeks), seedling height (2-8 weeks) and dry
      weight (2-8 weeks). The application of Epichloe endophyte culture supernatants
      was an effective strategy to improve seed germination and growth under greenhouse
      conditions.

PMID- 29375495
TI  - Virome Characterization of a Collection of S. sclerotiorum from Australia.
AB  - Sclerotinia sclerotiorum is a devastating plant pathogen that attacks numerous
      economically important broad acre and vegetable crops worldwide. Mycoviruses are
      widespread viruses that infect fungi, including S. sclerotiorum. As there were no
      previous reports of the presence of mycoviruses in this pathogen in Australia,
      studies were undertaken using RNA_Seq analysis to determine the diversity of
      mycoviruses in 84 Australian S. sclerotiorum isolates collected from various
      hosts. After RNA sequences were subjected to BLASTp analysis using NCBI database,
      285 contigs representing partial or complete genomes of 57 mycoviruses were
      obtained, and 34 of these (59.6%) were novel viruses. These 57 viruses were
      grouped into 10 distinct lineages, namely Endornaviridae (four novel
      mycoviruses), Genomoviridae (isolate of SsHADV-1), Hypoviridae (two novel
      mycoviruses), Mononegavirales (four novel mycovirusess), Narnaviridae (10 novel
      mycoviruses), Partitiviridae (two novel mycoviruses), Ourmiavirus (two novel
      mycovirus), Tombusviridae (two novel mycoviruses), Totiviridae (one novel
      mycovirus), Tymovirales (five novel mycoviruses), and two non-classified
      mycoviruses lineages (one Botrytis porri RNA virus 1, one distantly related to
      Aspergillus fumigatus tetramycovirus-1). Twenty-five mitoviruses were determined
      and mitoviruses were dominant in the isolates tested. This is not only the first
      study to show existence of mycoviruses in S. sclerotiorum in Australia, but
      highlights how they are widespread and that many novel mycoviruses occur there.
      Further characterization of these mycoviruses is warranted, both in terms of
      exploring these novel mycoviruses for innovative biocontrol of Sclerotinia
      diseases and in enhancing our overall knowledge on viral diversity, taxonomy,
      ecology, and evolution.

PMID- 29375494
TI  - Prospects for Fungal Bioremediation of Acidic Radioactive Waste Sites:
      Characterization and Genome Sequence of Rhodotorula taiwanensis MD1149.
AB  - Highly concentrated radionuclide waste produced during the Cold War era is stored
      at US Department of Energy (DOE) production sites. This radioactive waste was
      often highly acidic and mixed with heavy metals, and has been leaking into the
      environment since the 1950s. Because of the danger and expense of cleanup of such
      radioactive sites by physicochemical processes, in situ bioremediation methods
      are being developed for cleanup of contaminated ground and groundwater. To date,
      the most developed microbial treatment proposed for high-level radioactive sites
      employs the radiation-resistant bacterium Deinococcus radiodurans. However, the
      use of Deinococcus spp. and other bacteria is limited by their sensitivity to low
      pH. We report the characterization of 27 diverse environmental yeasts for their
      resistance to ionizing radiation (chronic and acute), heavy metals, pH minima,
      temperature maxima and optima, and their ability to form biofilms. Remarkably,
      many yeasts are extremely resistant to ionizing radiation and heavy metals. They
      also excrete carboxylic acids and are exceptionally tolerant to low pH. A special
      focus is placed on Rhodotorula taiwanensis MD1149, which was the most resistant
      to acid and gamma radiation. MD1149 is capable of growing under 66 Gy/h at pH 2.3
      and in the presence of high concentrations of mercury and chromium compounds, and
      forming biofilms under high-level chronic radiation and low pH. We present the
      whole genome sequence and annotation of R. taiwanensis strain MD1149, with a
      comparison to other Rhodotorula species. This survey elevates yeasts to the
      frontier of biology's most radiation-resistant representatives, presenting a
      strong rationale for a role of fungi in bioremediation of acidic radioactive
      waste sites.

PMID- 29375496
TI  - iTRAQ-Based Proteomic Analysis of Sublethally Injured Escherichia coli O157:H7
      Cells Induced by High Pressure Carbon Dioxide.
AB  - High pressure carbon dioxide (HPCD) could cause sublethally injured cells (SICs),
      which may cause food poisoning and spoilage during food storage and limit its
      application. Therefore, the formation of SICs of Escherichia coli O157:H7 was
      investigated by isobaric tag for relative and absolute quantification (iTRAQ)
      proteomic methods in this study for better controlling the SICs induced by HPCD.
      A total of 2,446 proteins was identified by iTRAQ, of which 93 and 29 were
      significantly differentially expressed in the SICs compared with live control
      cells (CKL) and dead control cells (CKD), respectively. Among the 93
      differentially expressed proteins (DEP) in the SICs compared with CKL, 65
      proteins showed down-regulation and 28 showed up-regulation. According to the
      comprehensive proteome coverage analysis, the SICs survived under HPCD by
      reducing carbohydrate decomposing, lipid transport and metabolism, amino acid
      transport and metabolism, transcription and translation, DNA replication and
      repair. Besides, the SICs showed stress response, DNA damage response and an
      increased carbohydrate transport, peptidoglycan synthesis and disulfide bond
      formation to HPCD. Among the 29 DEP in the SICs compared with CKD, 12 proteins
      showed down-regulation and 17 showed up-regulation. According to the
      comprehensive proteome coverage analysis, the SICs survived under HPCD by
      accumulation of cell protective agents like carbohydrates and amino acids, and
      decreasing transcription and translation activities. Results showed that the
      formation of the SICs with low metabolic activity and high survival ability was a
      survival strategy for E. coli O157:H7 against HPCD.

PMID- 29375497
TI  - Abundance of Secreted Proteins of Trichoderma reesei Is Regulated by Light of
      Different Intensities.
AB  - In Trichoderma reesei light is an important factor in the regulation of glycoside
      hydrolase gene expression. We therefore investigated the influence of different
      light intensities on cellulase activity and protein secretion. Differentially
      secreted proteins in light and darkness as identified by mass spectrometry
      included members of different glycoside hydrolase families, such as CBH1, Cel3A,
      Cel61B, XYN2, and XYN4. Several of the associated genes showed light-dependent
      regulation on the transcript level. Deletion of the photoreceptor genes blr1 and
      blr2 resulted in a diminished difference of protein abundance between light and
      darkness. The amount of secreted proteins including that of the major exo-acting
      beta-1,4-glucanases CBH1 and CBH2 was generally lower in light-grown cultures
      than in darkness. In contrast, cbh1 transcript levels increased with increasing
      light intensity from 700 to 2,000 lux but dopped at high light intensity (5,000
      lux). In the photoreceptor mutants Deltablr1 and Deltablr2 cellulase activity in
      light was reduced compared to activity in darkness, showing a discrepancy between
      transcript levels and secreted cellulase activity. Furthermore, evaluation of
      different light sensitivities revealed an increased light tolerance with respect
      to cellulase expression of QM9414 compared to its parental strain QM6a.
      Investigation of one of the differentially expressed proteins between light and
      darkness, CLF1, revealed its function as a factor involved in regulation of
      secreted protease activity. T. reesei secretes a different set of proteins in
      light compared to darkness, this difference being mainly due to the function of
      the major known photoreceptors. Moreover, cellulase regulation is adjusted to
      light intensity and improved light tolerance was correlated with increased
      cellulase production. Our findings further support the hypothesis of a light
      intensity dependent post-transcriptional regulation of cellulase gene expression
      in T. reesei.

PMID- 29375498
TI  - In Vitro and in Silico Evidence of Phosphatase Diversity in the Biomineralizing
      Bacterium Ramlibacter tataouinensis.
AB  - Microbial phosphatase activity can trigger the precipitation of metal-phosphate
      minerals, a process called phosphatogenesis with global geochemical and
      environmental implications. An increasing diversity of phosphatases expressed by
      diverse microorganisms has been evidenced in various environments. However, it is
      challenging to link the functional properties of genomic repertoires of
      phosphatases with the phosphatogenesis capabilities of microorganisms. Here, we
      studied the betaproteobacterium Ramlibacter tataouinensis (Rta), known to
      biomineralize Ca-phosphates in the environment and the laboratory. We
      investigated the functional repertoire of this biomineralization process at the
      cell, genome and molecular level. Based on a mineralization assay, Rta is shown
      to hydrolyse the phosphoester bonds of a wide range of organic P molecules.
      Accordingly, its genome has an unusually high diversity of phosphatases: five
      genes belonging to two non-homologous families, phoD and phoX, were detected.
      These genes showed diverse predicted cis-regulatory elements. Moreover, they
      encoded proteins with diverse structural properties according to molecular
      models. Heterologously expressed PhoD and PhoX in Escherichia coli had different
      profiles of substrate hydrolysis. As evidenced for Rta cells, recombinant E. coli
      cells induced the precipitation of Ca-phosphate mineral phases, identified as
      poorly crystalline hydroxyapatite. The phosphatase genomic repertoire of Rta
      (containing phosphatases of both the PhoD and PhoX families) was previously
      evidenced as prevalent in marine oligotrophic environments. Interestingly, the
      Tataouine sand from which Rta was isolated showed similar P-depleted, but Ca-rich
      conditions. Overall, the diversity of phosphatases in Rta allows the hydrolysis
      of a broad range of organic P substrates and therefore the release of
      orthophosphates (inorganic phosphate) under diverse trophic conditions. Since the
      release of orthophosphates is key to the achievement of high saturation levels
      with respect to hydroxyapatite and the induction of phosphatogenesis, Rta appears
      as a particularly efficient driver of this process as shown experimentally.

PMID- 29375500
TI  - Experimental Aspects Suggesting a "Fluxus" of Information in the Virions of
      Herpes Simplex Virus Populations.
AB  - Our perspective on nature has changed throughout history and at the same time has
      affected directly or indirectly our perception of biological processes. In that
      sense, the "fluxus" of information in a viral population arises a result of a
      much more complex process than the encoding of a protein by a gene, but as the
      consequence of the interaction between all the components of the genome and its
      products: DNA, RNA, and proteins and its modulation by the environment. Even
      modest "agents of life" like viruses display an intricate way to express their
      information. This conclusion can be withdrawn from the huge quantity of data
      furnished by new and potent technologies available now to analyze viral
      populations. Based on this premise, evolutive processes for viruses are now
      interpreted as a simultaneous and coordinated phenomenon that leads to global
      (i.e., not gradual or 'random') remodeling of the population. Our system of study
      involves the modulation of herpes simplex virus populations through the selective
      pressure exerted by carrageenans, natural compounds that interfere with virion
      attachment to cells. On this line, we demonstrated that the passaging of virus in
      the presence of carrageenans leads to the appearance of progeny virus
      phenotipically different from the parental seed, particularly, the emergence of
      syncytial (syn) variants. This event precedes the emergence of mutations in the
      population which can be readily detected five passages after from the moment of
      the appearance of syn virus. This observation can be explained taking into
      consideration that the onset of phenotypic changes may be triggered by
      "environmental-sensitive" glycoproteins. These "environmental-sensitive"
      glycoproteins may act by themselves or may transmit the stimulus to "adapter"
      proteins, particularly, proteins of the tegument, which eventually modulate the
      expression of genomic products in the "virocell." The modulation of the RNA
      network is a common strategy of the virocell to respond to environmental changes.
      This "fast" adaptive mechanism is followed eventually by the appearance of
      mutations in the viral genome. In this paper, we interpret these findings from a
      philosophical and scientific point of view interconnecting epigenetic action,
      exerted by carragenans from early RNA network-DNA interaction to late DNA
      mutation. The complexity of HSV virion structure is an adequate platform to
      envision new studies on this topic that may be complemented in a near future
      through the analysis of the genetic dynamics of HSV populations.

PMID- 29375499
TI  - Identification of the Autochaperone Domain in the Type Va Secretion System
      (T5aSS): Prevalent Feature of Autotransporters with a beta-Helical Passenger.
AB  - Autotransporters (ATs) belong to a family of modular proteins secreted by the
      Type V, subtype a, secretion system (T5aSS) and considered as an important source
      of virulence factors in lipopolysaccharidic diderm bacteria (archetypical Gram
      negative bacteria). While exported by the Sec pathway, the ATs are further
      secreted across the outer membrane via their own C-terminal translocator forming
      a beta-barrel, through which the rest of the protein, namely the passenger, can
      pass. In several ATs, an autochaperone domain (AC) present at the C-terminal
      region of the passenger and upstream of the translocator was demonstrated as
      strictly required for proper secretion and folding. However, considering it was
      functionally characterised and identified only in a handful of ATs, wariness
      recently fells on the commonality and conservation of this structural element in
      the T5aSS. To circumvent the issue of sequence divergence and taking advantage of
      the resolved three-dimensional structure of some ACs, identification of this
      domain was performed following structural alignment among all AT passengers
      experimentally resolved by crystallography before searching in a dataset of 1523
      ATs. While demonstrating that the AC is indeed a conserved structure found in
      numerous ATs, phylogenetic analysis further revealed a distribution into deeply
      rooted branches, from which emerge 20 main clusters. Sequence analysis revealed
      that an AC could be identified in the large majority of SAATs (self-associating
      ATs) but not in any LEATs (lipase/esterase ATs) nor in some PATs (protease
      autotransporters) and PHATs (phosphatase/hydrolase ATs). Structural analysis
      indicated that an AC was present in passengers exhibiting single-stranded right
      handed parallel beta-helix, whatever the type of beta-solenoid, but not with
      alpha-helical globular fold. From this investigation, the AC of type 1 appears as
      a prevalent and conserved structural element exclusively associated to beta
      helical AT passenger and should promote further studies about the protein
      secretion and folding via the T5aSS, especially toward alpha-helical AT
      passengers.

PMID- 29375501
TI  - Impact of Seed Exudates on Growth and Biofilm Formation of Bacillus
      amyloliquefaciens ALB629 in Common Bean.
AB  - We aimed to unravel the events which favor the seed-rhizobacterium Bacillus
      amyloliquefaciens strain ALB629 (hereafter ALB629) interaction and which may
      interfere with the rhizobacterium colonization and growth on the spermosphere of
      common bean. Seed exudates from common bean were tested in vitro for ALB629
      biofilm formation and bacterial growth. Furthermore, the performance of ALB629 on
      plant-related variables under drought stress was checked. Seed exudates (1 and 5%
      v/v) increased ALB629 biofilm formation. Additionally, the colony forming units
      for ALB629 increased both in culture and on the bean seed surface. The bean seed
      exudates up-regulated biofilm operons in ALB629 TasA and EpsD by ca. two and
      sixfold, respectively. The high-performance liquid chromatography (HPLC)-coupled
      with MS showed that malic acid is present as a major organic acid component in
      the seed exudates. Seeds treated with ALB629 and amended with malic acid resulted
      in seedlings with a higher bacterial concentration, induced plant drought
      tolerance, and promoted plant growth. We showed that seed exudates promote growth
      of ALB629 and malic acid was identified as a major organic acid component in the
      bean seed exudates. Our results also show that supplementation of ALB629 induced
      drought tolerance and growth in plants. The research pertaining to the biological
      significance of seed exudates in plant-microbe interaction is unexplored field
      and our work shows the importance of seed exudates in priming both growth and
      tolerance against abiotic stress.

PMID- 29375502
TI  - Yeast Starter as a Biotechnological Tool for Reducing Copper Content in Wine.
AB  - Copper is widely used in agriculture as a traditional fungicide in organic
      farming to control downy mildew on grapes, consequently it is possible to find
      this metal during all stages of the vinification process. Low amounts of copper
      play a key role on the function of key cell enzymes, whereas excess quantities
      can exert amount-dependent cytotoxicity, resulting in general cellular damage.
      Nowadays the excessive copper ions in wines is removed by addition of adsorbents,
      but these additives can influence the sensory characteristics of wine, as well as
      detrimental to the health of consumers. It is well known that high concentrations
      of Cu2+ can be toxic to yeasts, inhibiting growth and activity, causing sluggish
      fermentation and reducing alcohol production. In this study, 47 S. cerevisiae
      strains were tested for copper tolerance by two different tests, growth on copper
      added medium and fermentative activity in copper added grape must. The results
      obtained by the two different tests were comparable and the high strain
      variability found was used to select four wild strains, possessing this
      characteristic at the highest (PP1-13 and A20) and the lowest level (MPR2-24 and
      A13). The selected strains were tested in synthetic and natural grape must
      fermentation for ability to reduce copper content in wine. The determination of
      copper content in wines and yeast cells revealed that at the lowest copper
      residual in wine corresponded the highest content in yeast cells, indicating a
      strong strain ability to reduce the copper content in wine. This effect was
      inversely correlated with strain copper resistance and the most powerful strain
      in copper reduction was the most sensitive strain, MPR2-24. This wild strain was
      finally tested as starter culture in cellar pilot scale fermentation in
      comparison to a commercial starter, confirming the behavior exhibited at lab
      scale. The use of this wild strain to complete the alcoholic fermentation and
      remove the copper from wine represents a biotechnological sustainable approach,
      as alternative to the chemical-physical methods, ensuring at the same time a
      completed alcoholic fermentation and organoleptic quality of wine.

PMID- 29375503
TI  - Bovine Lactoferrin and Lactoferrin-Derived Peptides Inhibit the Growth of Vibrio
      cholerae and Other Vibrio species.
AB  - Vibrio is a genus of Gram-negative bacteria, some of which can cause serious
      infectious diseases. Vibrio infections are associated with the consumption of
      contaminated food and classified in Vibrio cholera infections and non-cholera
      Vibrio infections. In the present study, we investigate whether bovine
      lactoferrin (bLF) and several synthetic peptides corresponding to bLF sequences,
      are able to inhibit the growth or have bactericidal effect against V. cholerae
      and other Vibrio species. The antibacterial activity of LF and LF-peptides was
      assessed by kinetics of growth or determination of colony forming unit in
      bacteria treated with the peptides and antibiotics. To get insight in the mode of
      action, the interaction between bLF and bLF-peptides (coupled to FITC) and V.
      cholera was evaluated. The damage of effector-induced bacterial membrane
      permeability was measured by inclusion of the fluorescent dye propidium iodide
      using flow cytometry, whereas the bacterial ultrastructural damage in bacteria
      treated was observed by transmission electron microscopy. The results showed that
      bLF and LFchimera inhibited the growth of the V. cholerae strains; LFchimera
      permeabilized the bacteria which membranes were seriously damaged. Assays with a
      multidrug-resistant strain of Vibrio species indicated that combination of sub
      lethal doses of LFchimera with ampicillin or tetracycline strongly reduced the
      concentration of the antibiotics to reach 95% growth inhibition. Furthermore,
      LFchimera were effective to inhibit the V. cholerae counts and damage due to this
      bacterium in a model mice. These data suggest that LFchimera and bLF are
      potential candidates to combat the V. cholerae and other multidrug resistant
      Vibrio species.

PMID- 29375504
TI  - Probing the Structures of Viral RNA Regulatory Elements with SHAPE and Related
      Methodologies.
AB  - Viral RNAs were selected by evolution to possess maximum functionality in a
      minimal sequence. Depending on the classification of the virus and the type of
      RNA in question, viral RNAs must alternately be replicated, spliced, transcribed,
      transported from the nucleus into the cytoplasm, translated and/or packaged into
      nascent virions, and in most cases, provide the sequence and structural
      determinants to facilitate these processes. One consequence of this compact
      multifunctionality is that viral RNA structures can be exquisitely complex, often
      involving intermolecular interactions with RNA or protein, intramolecular
      interactions between sequence segments separated by several thousands of
      nucleotides, or specialized motifs such as pseudoknots or kissing loops. The
      fluidity of viral RNA structure can also present a challenge when attempting to
      characterize it, as genomic RNAs especially are likely to sample numerous
      conformations at various stages of the virus life cycle. Here we review advances
      in chemoenzymatic structure probing that have made it possible to address such
      challenges with respect to cis-acting elements, full-length viral genomes and
      long non-coding RNAs that play a major role in regulating viral gene expression.

PMID- 29375505
TI  - The Role of NADPH Oxidase in the Inhibition of Trichophyton rubrum by 420-nm
      Intense Pulsed Light.
AB  - Objectives: To evaluate the effect of intense pulsed light (IPL) on Trichophyton
      rubrum and investigate its mechanism of action. Methods: The viability of fungi
      treated with IPL alone and with IPL combined with an NADPH oxidase inhibitor
      (DPI) pretreatment was determined by MTT assays. The reactive oxygen species
      (ROS) were quantified with a DCFH-DA fluorescent probe. Malondialdehyde (MDA)
      content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)
      activities were determined by commercial kits. The transcription of the Nox gene
      was quantified using quantitative real-time PCR (qRT-PCR) analysis, and
      micromorphology was observed using scanning electron microscopy (SEM). In
      addition, fungal keratinase activity was detected by measuring dye release from
      keratin azure. Results: The growth declined with statistical significance after 6
      h of treatment (P < 0.001). The ROS and MDA content increased after IPL
      treatment, whereas the SOD and GSH-Px activity decreased. Nox gene expression was
      upregulated, and the micromorphology was damaged. Keratinase activity decreased.
      Fungi that received DPI pretreatment exhibited contrasting outcomes. Conclusion:
      We found that 420-nm IPL significantly inhibited the growth and pathogenicity of
      T. rubrum in vitro. A suggested mechanism involves Nox as a factor that mediates
      420-nm IPL-induced oxidative damage of T. rubrum.

PMID- 29375506
TI  - Genomic Analysis of Two Phylogenetically Distinct Nitrospira Species Reveals
      Their Genomic Plasticity and Functional Diversity.
AB  - The genus Nitrospira represents a dominant group of nitrite-oxidizing bacteria in
      natural and engineered ecosystems. This genus is phylogenetically divided into
      six lineages, for which vast phylogenetic and functional diversity has been
      revealed by recent molecular ecophysiological analyses. However, the genetic
      basis underlying these phenotypic differences remains largely unknown because of
      the lack of genome sequences representing their diversity. To gain a more
      comprehensive understanding of Nitrospira, we performed genomic comparisons
      between two Nitrospira strains (ND1 and NJ1 belonging to lineages I and II,
      respectively) previously isolated from activated sludge. In addition, the genomes
      of these strains were systematically compared with previously reported six
      Nitrospira genomes to reveal their similarity and presence/absence of several
      functional genes/operons. Comparisons of Nitrospira genomes indicated that their
      genomic diversity reflects phenotypic differences and versatile nitrogen
      metabolisms. Although most genes involved in key metabolic pathways were
      conserved between strains ND1 and NJ1, assimilatory nitrite reduction pathways of
      the two Nitrospira strains were different. In addition, the genomes of both
      strains contain a phylogenetically different urease locus and we confirmed their
      ureolytic activity. During gene annotation of strain NJ1, we found a gene cluster
      encoding a quorum-sensing system. From the enriched supernatant of strain NJ1, we
      successfully identified seven types of acyl-homoserine lactones with a range of
      C10-C14. In addition, the genome of strain NJ1 lacks genes relevant to flagella
      and the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas
      (CRISPR-associated genes) systems, whereas most nitrifying bacteria including
      strain ND1 possess these genomic elements. These findings enhance our
      understanding of genomic plasticity and functional diversity among members of the
      genus Nitrospira.

PMID- 29375507
TI  - Phagocytic and Bactericidal Properties of Channel Catfish Peritoneal Macrophages
      Exposed to Edwardsiella ictaluri Live Attenuated Vaccine and Wild-Type Strains.
AB  - Edwardsiella ictaluri (E. ictaluri), a Gram-negative, intracellular, facultative
      bacterium, is the causative agent of enteric septicemia of catfish (ESC), which
      is one of the most significant diseases of farmed channel catfish. Macrophages
      have a critical role in major defense mechanisms against bacterial infections by
      migrating to the site of infection, engulfing and killing pathogens, and priming
      adaptive immune responses. Vaccination of catfish with E. ictaluri live
      attenuated vaccine (LAV) strains increased the efficiency of phagocytosis and
      bacterial killing in catfish peritoneal macrophages compared in vitro with
      macrophages from non-vaccinated fish. Recently, our group developed several
      protective LAV strains from E. ictaluri. However, their effects on the antigen
      uptake and bacterial killing in catfish macrophages have not been evaluated. In
      this study, we assessed the phagocytic and bactericidal activity of peritoneal
      macrophages in the uptake of E. ictaluri wild-type (WT) and two LAV strains. We
      found that phagocytosis of LAV strains was significantly higher compared to their
      WT counterpart in peritoneal macrophages. Moreover, the uptake of E. ictaluri
      opsonized with sera from vaccinated catfish was more efficient than when
      opsonized with sera from sham-vaccinated fish. Notably, catfish macrophages did
      not lose their phagocytic properties at 4 degrees C, as described previously in
      mammalian and zebrafish models. Also, opsonization of E. ictaluri with
      inactivated sera from vaccinated and sham-vaccinated catfish decreased
      significantly phagocytic uptake of bacteria at 32 degrees C, and virtually
      suppressed endocytosis at 4 degrees C, suggesting the important role of
      complement-dependent mechanisms in catfish macrophage phagocytosis. In
      conclusion, our data on enhanced phagocytic capacity and effective killing
      ability in macrophages of vaccine strains suggested the LAVs' advantage if
      processed and presented in the form of peptides to specific lymphocytes of an
      adaptive immune system and emphasize the importance of macrophage-mediated
      immunity against ESC. Furthermore, we showed the role of complement-dependent
      mechanisms in the phagocytic uptakes of E. ictaluri in catfish peritoneal
      macrophages at 4 and 32 degrees C. Finally, LAV vaccine-induced bacterial
      phagocytosis and killing properties of peritoneal macrophages emphasized the
      importance of the innate immune responses in ESC.

PMID- 29375508
TI  - Breast Milk Is a Potential Reservoir for Livestock-Associated Staphylococcus
      aureus and Community-Associated Staphylococcus aureus in Shanghai, China.
AB  - Breast milk is the first choice in feeding newborn infants and provides multiple
      benefits for their growth and development. Staphylococcus aureus usually exists
      in breast milk and is considered one of the most important causative infective
      agents. To be effective in preventing and controlling S. aureus infections among
      infants, the aim of this study was to determine the occurrence and molecular
      characteristics of S. aureus isolated from 1102 samples of breast milk between
      2015 and 2016 in Shanghai, China. Out of 71 S. aureus strains isolated, 15
      (21.1%, 15/71) were MRSA and all the strains were characterized by spa typing,
      Multi-Locus Sequence Typing, SCCmec typing, antibiotic resistance testing and
      virulence-associated genes. A total of 18 distinct sequence types (STs) and 36
      spa types were identified within the 71 isolates, among which the most frequently
      represented was ST398 (19.7%, 14/71), followed by ST7 (18.3%, 13/71), ST59
      (16.9%, 12/71). The three predominant STs accounted for more than one half of all
      S. aureus isolates. The most prevalent spa types were t091 (12.7%, 9/71),
      followed by t571 (8.5%, 6/71), t189 (7.0%, 5/71), t034 (5.6%, 4/71), t437 (5.6%,
      4/71), and t701 (4.2%, 3/71). All MRSA isolates belonged to SCCmec IV and V,
      accounting for 66.7 and 33.3% respectively. Notably, 23 (32.4%) S. aureus strains
      were multidrug resistance (MDR), including 4 (5.6%) MRSA and 19 (26.8%) MSSA
      strains, and MDR isolates were mostly resistant to penicillin, erythromycin and
      clindamycin. All isolates exhibited simultaneous carriage of at least 5 of 33
      possible virulence genes and the most prevalent genes detected were icaA (100%),
      clfA (100%), hla (100%), sdrC (94.4%), hlg2 (88.7%), lukE (57.8%). 39 (54.9%,
      39/71) isolates, including 9 (12.7%) of MRSA isolates, harbored >=10 tested
      virulence genes evaluated in this study. The pvl gene was detected in 8 strains,
      which represented 5 different STs, with ST59 being the most one. Overall, our
      findings showed that S. aureus strains isolated from breast milk were mainly MSSA
      (78.9%, 56/71) and exhibited high genetic diversity in Shanghai area of China.
      Breast milk was a reservoir for LA-SA (ST398) and CA-SA (ST59), which was likely
      a vehicle for transmission of multidrug-resistant S. aureus and MRSA lineages.
      This is a potential public health risk and highlights the need for good hygiene
      practices to reduce the risk of infant infections.

PMID- 29375509
TI  - Phytochemicals from Camellia nitidissima Chi Flowers Reduce the Pyocyanin
      Production and Motility of Pseudomonas aeruginosa PAO1.
AB  - Camellia nitidissima Chi, known as a medicinal and edible plant in China,
      exhibits multiple bioactivities, especially antibacterial activity. In this
      study, we investigated the inhibitory effects of the dichloromethane fraction
      (DF) of C. nitidissima Chi flowers on the pyocyanin production, swarming
      motility, and swimming motility of Pseudomonas aeruginosa PAO1, at sub-minimum
      inhibitory concentrations. Results showed that the DF had a remarkable inhibitory
      effect on pyocyanin production without influencing P. aeruginosa PAO1 growth, and
      concentration-dependent inhibitory effects on swarming and swimming motility. The
      half maximal inhibitory concentrations (IC50) were 0.158 +/- 0.009, 0.139 +/-
      0.004, and 0.334 +/- 0.049 mg/mL for pyocyanin production, swarming motility, and
      swimming motility, respectively. Real-time RT-PCR showed that the DF
      significantly down-regulated the expressions of lasR (p < 0.05) and rhlR (p <
      0.01). In addition, gallic acid, catechin, ellagic acid, chlorogenic acid,
      quercetin, and kaempferol were identified in the DF by HPLC Triple TOF MS/MS
      analysis. All six identified compounds showed inhibitory effects on pyocyanin
      production, swarming motility, and swimming motility, though ellagic acid showed
      the strongest effects, with IC50 values of 0.067 +/- 0.002, 0.024 +/- 0.008, and
      0.020 +/- 0.003 mg/mL, respectively. Thus, the inhibitory effects on P.
      aeruginosa PAO1 virulence factors might be attributable to these six and/or other
      compounds in the DF of C. nitidissima Chi flowers. Consequently, the C.
      nitidissima Chi flower, especially the DF, might be a potential quorum sensing
      inhibitor of P. aeruginosa PAO1.

PMID- 29375510
TI  - Differential NtcA Responsiveness to 2-Oxoglutarate Underlies the Diversity of C/N
      Balance Regulation in Prochlorococcus.
AB  - Previous studies showed differences in the regulatory response to C/N balance in
      Prochlorococcus with respect to other cyanobacteria, but no information was
      available about its causes, or the ecological advantages conferred to thrive in
      oligotrophic environments. We addressed the changes in key enzymes (glutamine
      synthetase, isocitrate dehydrogenase) and the ntcA gene (the global nitrogen
      regulator) involved in C/N metabolism and its regulation, in three model
      Prochlorococcus strains: MED4, SS120, and MIT9313. We observed a remarkable level
      of diversity in their response to azaserine, a glutamate synthase inhibitor which
      increases the concentration of the key metabolite 2-oxoglutarate, used to sense
      the C/N balance by cyanobacteria. Besides, we studied the binding between the
      global nitrogen regulator (NtcA) and the promoter of the glnA gene in the same
      Prochlorococcus strains, and its dependence on the 2-oxoglutarate concentration,
      by using isothermal titration calorimetry, surface plasmon resonance, and
      electrophoretic mobility shift. Our results show a reduction in the
      responsiveness of NtcA to 2-oxoglutarate in Prochlorococcus, especially in the
      MED4 and SS120 strains. This suggests a trend to streamline the regulation of C/N
      metabolism in late-branching Prochlorococcus strains (MED4 and SS120), in
      adaptation to the rather stable conditions found in the oligotrophic ocean gyres
      where this microorganism is most abundant.

PMID- 29375511
TI  - Identification, Comparison, and Validation of Robust Rumen Microbial Biomarkers
      for Methane Emissions Using Diverse Bos Taurus Breeds and Basal Diets.
AB  - Previous shotgun metagenomic analyses of ruminal digesta identified some
      microbial information that might be useful as biomarkers to select cattle that
      emit less methane (CH4), which is a potent greenhouse gas. It is known that
      methane production (g/kgDMI) and to an extent the microbial community is
      heritable and therefore biomarkers can offer a method of selecting cattle for low
      methane emitting phenotypes. In this study a wider range of Bos Taurus cattle,
      varying in breed and diet, was investigated to determine microbial communities
      and genetic markers associated with high/low CH4 emissions. Digesta samples were
      taken from 50 beef cattle, comprising four cattle breeds, receiving two basal
      diets containing different proportions of concentrate and also including feed
      additives (nitrate or lipid), that may influence methane emissions. A combination
      of partial least square analysis and network analysis enabled the identification
      of the most significant and robust biomarkers of CH4 emissions (VIP > 0.8) across
      diets and breeds when comparing all potential biomarkers together. Genes
      associated with the hydrogenotrophic methanogenesis pathway converting carbon
      dioxide to methane, provided the dominant biomarkers of CH4 emissions and
      methanogens were the microbial populations most closely correlated with CH4
      emissions and identified by metagenomics. Moreover, these genes grouped together
      as confirmed by network analysis for each independent experiment and when
      combined. Finally, the genes involved in the methane synthesis pathway explained
      a higher proportion of variation in CH4 emissions by PLS analysis compared to
      phylogenetic parameters or functional genes. These results confirmed the
      reproducibility of the analysis and the advantage to use these genes as robust
      biomarkers of CH4 emissions. Volatile fatty acid concentrations and ratios were
      significantly correlated with CH4, but these factors were not identified as
      robust enough for predictive purposes. Moreover, the methanotrophic Methylomonas
      genus was found to be negatively correlated with CH4. Finally, this study
      confirmed the importance of using robust and applicable biomarkers from the
      microbiome as a proxy of CH4 emissions across diverse production systems and
      environments.

PMID- 29375512
TI  - Comparative Genomics of Thalassobius Including the Description of Thalassobius
      activus sp. nov., and Thalassobius autumnalis sp. nov.
AB  - A taxogenomic study was conducted to describe two new Thalassobius species and to
      analyze the internal consistency of the genus Thalassobius along with Shimia and
      Thalassococcus. Strains CECT 5113T, CECT 5114, CECT 5118T, and CECT 5120 were
      isolated from coastal Mediterranean seawater, Spain. Cells were Gram-negative,
      non- motile coccobacilli, aerobic chemoorganotrophs, with an optimum temperature
      of 26 degrees C and salinity of 3.5-5%. Major cellular fatty acids of strains
      CECT 5113T and CECT 5114 were C18 : 1 omega7c/omega6c and C10 : 0 3OH, G+C
      content was 54.4-54.5 mol% and were able to utilize propionate, L-threonine, L-
      arginine, and L-aspartate as carbon sources. They exhibited 98.3% 16S rRNA gene
      sequence similarity, 75.0-75.1 ANIb and 19.5-20.9 digital DDH to type strain of
      their closest species, Thalassobius maritimus. Based on these data, strains CECT
      5113T and CECT 5114 are recognized as a new species, for which the name
      Thalassobius activus is proposed, with strain CECT 5113T (=LMG 29900T) as type
      strain. Strains CECT 5118T and CECT 5120 were found to constitute another new
      species, with major cellular fatty acids C18 : 1 omega7c/omega6c and C18 : 1
      omega7c 11-methyl and a G+C content of 59.8 mol%; they were not able to utilize
      propionate, L-threonine, L- arginine or L-aspartate. Their closest species was
      Thalassobius mediterraneus, with values of 99.6% 16S rRNA gene sequence
      similarity, 79.1% ANIb and 23.2% digital DDH compared to the type strain, CECT
      5383T. The name Thalassobius autumnalis is proposed for this second new species,
      with strain CECT 5118T (=LMG 29904T) as type strain. To better determine the
      phylogenetic relationship of the two new species, we submitted 12 genomes
      representing species of Thalassobius, Shimia, and Thalassoccocus, to a
      phylogenomic analysis based on 54 single protein-encoding genes (BCG54). The
      resulting phylogenomic tree did not agree with the current genera classification,
      as Thalassobius was divided in three clades, Thalassobius sensu stricto (T.
      mediterraneus, T. autumnalis sp. nov., and T. gelatinovorus), Thalassobius
      aestuarii plus the three Shimia spp (S. marina, S. haliotis, and Shimia sp.
      SK013) and finally, Thalasobius maritimus plus T. activus sp. nov. Thalassococcus
      halodurans remained apart from the two genera. Phenotypic inferences from
      explored genomes are presented.

PMID- 29375513
TI  - High Hydrostatic Pressure Inducible Trimethylamine N-Oxide Reductase Improves the
      Pressure Tolerance of Piezosensitive Bacteria Vibrio fluvialis.
AB  - High hydrostatic pressure (HHP) exerts severe effects on cellular processes
      including impaired cell division, abolished motility and affected enzymatic
      activities. Transcriptomic and proteomic analyses showed that bacteria switch the
      expression of genes involved in multiple energy metabolism pathways to cope with
      HHP. We sought evidence of a changing bacterial metabolism by supplying
      appropriate substrates that might have beneficial effects on the bacterial
      lifestyle at elevated pressure. We isolated a piezosensitive marine bacterium
      Vibrio fluvialis strain QY27 from the South China Sea. When trimethylamine N
      oxide (TMAO) was used as an electron acceptor for energy metabolism, QY27
      exhibited a piezophilic-like phenotype with an optimal growth at 30 MPa. Raman
      spectrometry and biochemistry analyses revealed that both the efficiency of the
      TMAO metabolism and the activity of the TMAO reductase increased under high
      pressure conditions. Among the two genes coding for TMAO reductase catalytic
      subunits, the expression level and enzymatic activity of TorA was up-regulated by
      elevated pressure. Furthermore, a genetic interference assay with the CRISPR
      dCas9 system demonstrated that TorA is essential for underpinning the improved
      pressure tolerance of QY27. We extended the study to Vibrio fluvialis type strain
      ATCC33809 and observed the same phenotype of TMAO-metabolism improved the
      pressure tolerance. These results provide compelling evidence for the determinant
      role of metabolism in the adaption of bacteria to the deep-sea ecosystems with
      HHP.

PMID- 29375514
TI  - Metabolomics Investigation of an Association of Induced Features and
      Corresponding Fungus during the Co-culture of Trametes versicolor and Ganoderma
      applanatum.
AB  - The co-culture of Trametes versicolor and Ganoderma applanatum is a model of
      intense basidiomycete interaction, which induces many newly synthesized or highly
      produced features. Currently, one of the major challenges is an identification of
      the origin of induced features during the co-culture. Herein, we report a 13C
      dynamic labeling analysis used to determine an association of induced features
      and corresponding fungus even if the identities of metabolites were not available
      or almost nothing was known of biochemical aspects. After the co-culture of T.
      versicolor and G. applanatum for 10 days, the mycelium pellets of T. versicolor
      and G. applanatum were sterilely harvested and then mono-cultured in the liquid
      medium containing half fresh medium with 13C-labeled glucose as carbon source and
      half co-cultured supernatants collected on day 10. 13C-labeled metabolome
      analyzed by LC-MS revealed that 31 induced features including 3-phenyllactic acid
      and orsellinic acid were isotopically labeled in the mono-culture after the co
      culture stimulation. Twenty features were derived from T. versicolor, 6 from G.
      applanatum, and 5 features were synthesized by both T. versicolor and G.
      applanatum. 13C-labeling further suggested that 12 features such as previously
      identified novel xyloside [N-(4-methoxyphenyl)formamide 2-O-beta-D-xyloside] were
      likely induced through the direct physical interaction of mycelia. Use of
      molecular network analysis combined with 13C-labeling provided an insight into
      the link between the generation of structural analogs and producing fungus.
      Compound 1 with m/z 309.0757, increased 15.4-fold in the co-culture and observed
      13C incorporation in the mono-culture of both T. versicolor and G. applanatum,
      was purified and identified as a phenyl polyketide, 2,5,6-trihydroxy-4, 6
      diphenylcyclohex-4-ene-1,3-dione. The biological activity study indicated that
      this compound has a potential to inhibit cell viability of leukemic cell line
      U937. The current work sets an important basis for further investigations
      including novel metabolites discovery and biosynthetic capacity improvement.

PMID- 29375515
TI  - Detection of Merkel Cell Polyomavirus in Seborrheic Keratosis.
AB  - Seborrheic keratosis (SK) is the most common benign cutaneous neoplasm. A subset
      shows increased p16 expression. Since SK shares several features with verruca
      vulgaris, e.g., increased p16 expression, human papillomaviruses (HPV) have been
      suggested as possible causal agents. However, a relevant association could not be
      established between HPV and SK. In the present study we aimed to investigate the
      presence of Merkel cell polyomavirus (MCPyV) in relation to p16 expression in SK.
      P16 expression was investigated using immunohistochemistry (IHC). Presence of
      MCPyV was assessed in 23 formalin-fixed paraffin-embedded tissue samples of SK by
      molecular techniques (i.e., PCR and FISH) and IHC. 16/23 SK showed strong to
      moderate p16 expression. 6/23 of SK were MCPyV positive by PCR which was
      confirmed by FISH. Of interest, two samples with strong FISH signals also showed
      MCPyV expression as tested by IHC. Samples with weaker signal intensity were
      negative in IHC. P16 expression was not associated with the presence of MCPyV.
      Concluding, the detection of MCPyV DNA by PCR and FISH in SK reflects the
      widespread prevalence of MCPyV in the skin. However, low detection rates exclude
      MCPyV as a major pathogenic factor in SK, most likely representing a coincidental
      infection. P16 IHC does not appear as useful adjunctive surrogate marker for the
      presence of MCPyV in SK.

PMID- 29375516
TI  - Synergistic Interactions within a Multispecies Biofilm Enhance Individual Species
      Protection against Grazing by a Pelagic Protozoan.
AB  - Biofilm formation has been shown to confer protection against grazing, but little
      information is available on the effect of grazing on biofilm formation and
      protection in multispecies consortia. With most biofilms in nature being composed
      of multiple bacterial species, the interactions and dynamics of a multispecies
      bacterial biofilm subject to grazing by a pelagic protozoan predator were
      investigated. To this end, a mono and multispecies biofilms of four bacterial
      soil isolates, namely Xanthomonas retroflexus, Stenotrophomonas rhizophila,
      Microbacterium oxydans and Paenibacillus amylolyticus, were constructed and
      subjected to grazing by the ciliate Tetrahymena pyriformis. In monocultures,
      grazing strongly reduced planktonic cell numbers in P. amylolyticus and S.
      rhizophila and also X. retroflexus. At the same time, cell numbers in the
      underlying biofilms increased in S. rhizophila and X. retroflexus, but not in P.
      amylolyticus. This may be due to the fact that while grazing enhanced biofilm
      formation in the former two species, no biofilm was formed by P. amylolyticus in
      monoculture, either with or without grazing. In four-species biofilms, biofilm
      formation was higher than in the best monoculture, a strong biodiversity effect
      that was even more pronounced in the presence of grazing. While cell numbers of
      X. retroflexus, S. rhizophila, and P. amylolyticus in the planktonic fraction
      were greatly reduced in the presence of grazers, cell numbers of all three
      species strongly increased in the biofilm. Our results show that synergistic
      interactions between the four-species were important to induce biofilm formation,
      and suggest that bacterial members that produce more biofilm when exposed to the
      grazer not only protect themselves but also supported other members which are
      sensitive to grazing, thereby providing a "shared grazing protection" within the
      four-species biofilm model. Hence, complex interactions shape the dynamics of the
      biofilm and enhance overall community fitness under stressful conditions such as
      grazing. These emerging inter- and intra-species interactions could play a vital
      role in biofilm dynamics in natural environments like soil or aquatic systems.

PMID- 29375517
TI  - Interactions of Alphavirus nsP3 Protein with Host Proteins.
AB  - Alphaviruses are members of the Togaviridae family and are grouped into two
      categories: arthritogenic and encephalitic. Arthritogenic alphavirus infections,
      as the name implies, are associated with arthritic outcomes while encephalitic
      alphavirus infections can lead to encephalitic outcomes in the infected host. Of
      the non-structural proteins (nsPs) that the viruses code for, nsP3 is the least
      understood in terms of function. Alphavirus nsP3s are characterized by regions
      with significantly conserved domain structure along with regions of high
      variability. Interactions of nsP3 with several host proteins have been documented
      including, stress granule-related proteins, dead box proteins, heat shock
      proteins, and kinases. In some cases, in addition to the interaction, requirement
      of the interaction to support infection has been demonstrated. An understanding
      of the proteomic network of nsP3 and the mechanisms by which these interactions
      support the establishment of a productive infection would make alphavirus nsP3 an
      interesting target for design of effective medical countermeasures.

PMID- 29375518
TI  - Rifampicin-Manuka Honey Combinations Are Superior to Other Antibiotic-Manuka
      Honey Combinations in Eradicating Staphylococcus aureus Biofilms.
AB  - Chronic wound infections are a major burden to both society and the health care
      industry. Bacterial biofilms are the major cause of chronic wound infections and
      are notoriously recalcitrant to treatments with antibiotics, making them
      difficult to eradicate. Thus, new approaches are required to combat biofilms in
      chronic wounds. One possible approach is to use drug combination therapies.
      Manuka honey has potent broad-spectrum antibacterial activity and has previously
      shown synergistic activity in combination with antibiotics against common wound
      pathogens, including Staphylococcus aureus. In addition, manuka honey exhibits
      anti-biofilm activity, thereby warranting the investigation of its potential as a
      combination therapy with antibiotics for the topical treatment of biofilm-related
      infections. Here we report the first use of MacSynergy II to investigate the
      response of established S. aureus (strain NCTC 8325) biofilms to treatment by
      combinations of Medihoney (medical grade manuka honey) and conventional
      antibiotics that are used for preventing or treating infections: rifampicin,
      oxacillin, fusidic acid, clindamycin, and gentamicin. Using checkerboard
      microdilution assays, viability assays and MacSynergy II analysis we show that
      the Medihoney-rifampicin combination was more effective than combinations using
      the other antibiotics against established staphylococcal biofilms. Medihoney and
      rifampicin were strongly synergistic in their ability to reduce both biofilm
      biomass and the viability of embedded S. aureus cells at a level that is likely
      to be significant in vivo. Other combinations of Medihoney and antibiotic
      produced an interesting array of effects: Medihoney-fusidic acid treatment showed
      minor synergistic activity, and Medihoney-clindamycin, -gentamicin, and 
      oxacillin combinations showed overall antagonistic effects when the honey was
      used at sub-inhibitory concentration, due to enhanced biofilm formation at these
      concentrations which could not be counteracted by the antibiotics. However, these
      combinations were not antagonistic when honey was used at the inhibitory
      concentration. Confocal scanning laser microscopy confirmed that different honey
      antibiotic combination treatments could eradicate biofilms. Our results suggest
      that honey has potential as an adjunct treatment with rifampicin for chronic
      wounds infected with staphylococcal biofilms. We also show that MacSynergy II
      allows a comprehensive examination of the synergistic effects of honey-antibiotic
      combinations, and can help to identify doses for clinical use.

PMID- 29375519
TI  - Additive Effects of Quorum Sensing Anti-Activators on Pseudomonas aeruginosa
      Virulence Traits and Transcriptome.
AB  - In the opportunistic pathogen Pseudomonas aeruginosa, quorum sensing (QS) via
      acyl-homoserine lactone (AHL) signals coordinates virulence gene expression. AHL
      signals must reach a critical threshold before enough is bound by cognate
      regulators LasR and RhlR to drive transcription of target genes. In addition,
      three anti-activator proteins, QteE, QscR, and QslA, sequester QS regulators to
      increase the threshold for induction and delay expression of QS target genes. It
      remains unclear how multiple anti-activators work together to achieve the quorum
      threshold. Here, we employed a combination of mutational, kinetic, phenotypic,
      and transcriptomic analysis to examine regulatory effects and interactions of the
      three distinct anti-activators. We observed combinatorial, additive effects on QS
      gene expression. As measured by reporter gene fusion, individual deletion of each
      anti-activator gene increased lasB expression and QS-controlled virulence factor
      production. Deletion of qslA in combination with the deletion of any other anti
      activator gene resulted in the greatest increase and earliest activation of lasB
      gene expression. Western analysis revealed that relative increases in soluble
      LasR in anti-activator mutants correlate with increased lasB expression and QS
      controlled virulence factor production. RNA-seq of the previously uncharacterized
      QslA and QteE regulons revealed overlapping, yet distinct groups of
      differentially expressed genes. Simultaneous inactivation of qteE and qslA had
      the largest effect on gene expression with 999 genes induced and 798 genes
      repressed in the double mutant vs. wild-type. We found that LasR and RhlR
      activated QS genes formed a subset of the genes induced in the qteE, qslA, and
      double mutant. The activation of almost all of these QS genes was advanced from
      stationary phase to log phase in the qteE qslA double mutant. Taken together, our
      results identify additive effects of anti-activation on QS gene expression,
      likely via LasR and RhlR, but do not rule out QS-independent effects.

PMID- 29375520
TI  - Aquaporin-4 Is Downregulated in the Basolateral Membrane of Ileum Epithelial
      Cells during Enterotoxigenic Escherichia coli-Induced Diarrhea in Mice.
AB  - Enterotoxigenic Escherichia coli (ETEC) are opportunistic pathogens that colonize
      the small intestine, produce enterotoxins and induce diarrhea. Some aquaporins
      (AQPs), such as AQP3 and AQP8, have been reported to participate in diarrhea by
      decreasing cellular influx in the gastrointestinal (GI) tract. AQP4 is another
      important water channel in the GI tract, but its role in ETEC-induced diarrhea
      has not been reported. Here, we demonstrated the potential roles of AQP4 in ETEC
      induced diarrhea. Reverse transcription-polymerase chain reaction (RT-PCR) and
      western blotting showed that AQP4 was expressed in the mouse ileum, but not in
      the duodenum or jejunum while immunohistochemical staining showed that AQP4
      localized to the basolateral membrane of ileum epithelial cells. Using an ETEC
      induced mice diarrhea model, we demonstrated that both AQP4 mRNA level and the
      AQP4 protein level in the ileum decreased gradually over a time course of 7 days.
      These results suggest that AQP4 plays a role in the pathogenesis of ETEC-induced
      diarrhea by mediating water transport.

PMID- 29375521
TI  - Investigation of the Role of Genes Encoding Zinc Exporters zntA, zitB, and fieF
      during Salmonella Typhimurium Infection.
AB  - The transition metal zinc is involved in crucial biological processes in all
      living organisms and is essential for survival of Salmonella in the host.
      However, little is known about the role of genes encoding zinc efflux
      transporters during Salmonella infection. In this study, we constructed deletion
      mutants for genes encoding zinc exporters (zntA, zitB, and fieF) in the wild-type
      (WT) strain Salmonella enterica serovar Typhimurium (S. Typhimurium) 4/74. The
      mutants 4/74DeltazntA and 4/74DeltazntA/zitB exhibited a dramatic growth delay
      and abrogated growth ability, respectively, in Luria Bertani medium supplemented
      with 0.25 mM ZnCl2 or 1.5 mM CuSO4 compared to the WT strain. In order to
      investigate the role of genes encoding zinc exporters on survival of S.
      Typhimurium inside cells, amoeba and macrophage infection models were used. No
      significant differences in uptake or survival were detected for any of the
      mutants compared to the WT during infection of amoebae. In natural resistance
      associated macrophage protein 1 (Nramp1)-negative J774.1 murine macrophages,
      significantly higher bacterial counts were observed for the mutant strains
      4/74DeltazntA and 4/74DeltazntA/zitB compared to the WT at 4 h post-infection
      although the fold net replication was similar between all the strains. All four
      tested mutants (4/74DeltazntA, 4/74DeltazitB, 4/74DeltafieF, and
      4/74DeltazntA/zitB) showed enhanced intracellular survival capacity within the
      modified Nramp1-positive murine RAW264.7 macrophages at 20 h post-infection. The
      fold net replication was also significantly higher for 4/74DeltazntA,
      4/74DeltazitB, and 4/74DeltazntA/zitB mutants compared to the WT. Intriguingly,
      the ability to survive and cause infection was significantly impaired in all the
      three mutants tested (4/74DeltazntA, 4/74DeltazitB, and 4/74DeltazntA/zitB) in
      C3H/HeN mice, particularly the double mutant 4/74DeltazntA/zitB was severely
      attenuated compared to the WT in all the three organs analyzed. These findings
      suggest that these genes encoding zinc exporters, especially zntA, contribute to
      the resistance of S. Typhimurium to zinc and copper stresses during infection.

PMID- 29375523
TI  - Quantitative Proteomic Analysis of Four Developmental Stages of Saprolegnia
      parasitica.
AB  - Several water mold species from the Saprolegnia genus infect fish, amphibians,
      and crustaceans in natural ecosystems and aquaculture farms. Saprolegnia
      parasitica is one of the most severe fish pathogens. It is responsible for
      millions of dollars of losses to the aquaculture industry worldwide. Here, we
      have performed a proteomic analysis, using gel-based and solution (iTRAQ)
      approaches, of four defined developmental stages of S. parasitica grown in vitro,
      i.e., the mycelium, primary cysts, secondary cysts and germinated cysts, to gain
      greater insight into the types of proteins linked to the different stages. A
      relatively high number of kinases as well as virulence proteins, including the
      ricin B lectin, disintegrins, and proteases were identified in the S. parasitica
      proteome. Many proteins associated with various biological processes were
      significantly enriched in different life cycle stages of S. parasitica. Compared
      to the mycelium, most of the proteins in the different cyst stages showed similar
      enrichment patterns and were mainly related to energy metabolism, signal
      transduction, protein synthesis, and post-translational modifications. The
      proteins most enriched in the mycelium compared to the cyst stages were
      associated with amino acid metabolism, carbohydrate metabolism, and mitochondrial
      energy production. The data presented expand our knowledge of metabolic pathways
      specifically linked to each developmental stage of this pathogen.

PMID- 29375524
TI  - Phage Therapy as a Promising New Treatment for Lung Infection Caused by
      Carbapenem-Resistant Acinetobacter baumannii in Mice.
AB  - Carbapenem-resistant Acinetobacter baumannii (CRAB) which is noted as a major
      pathogen associated with healthcare-associated infections has steadily developed
      beyond antibiotic control. Lytic bacteriophages with the characteristics of
      infecting and lysing specific bacteria have been used as a potential alternative
      to traditional antibiotics to solve multidrug-resistant bacterial infections.
      Here, we isolated A. baumannii-specific lytic phages and evaluated their
      potential therapeutic effect against lung infection caused by CRAB clinical
      strains. The combined lysis spectrum of four lytic phages' ranges was 87.5% (42
      of 48) against CRAB clinical isolates. Genome sequence and analysis indicated
      that phage SH-Ab15519 is a novel phage which does not contain the virulence or
      antibiotic resistance genes. In vivo study indicated that phage SH-Ab15519
      administered intranasally can effectively rescue mice from lethal A. baumannii
      lung infection without deleterious side effects. Our work explores the potential
      use of phages as an alternative therapeutic agent against the lung infection
      caused by CRAB strains.

PMID- 29375522
TI  - Identification of lptA, lpxE, and lpxO, Three Genes Involved in the Remodeling of
      Brucella Cell Envelope.
AB  - The brucellae are facultative intracellular bacteria that cause a worldwide
      extended zoonosis. One of the pathogenicity mechanisms of these bacteria is their
      ability to avoid rapid recognition by innate immunity because of a reduction of
      the pathogen-associated molecular pattern (PAMP) of the lipopolysaccharide (LPS),
      free-lipids, and other envelope molecules. We investigated the Brucella homologs
      of lptA, lpxE, and lpxO, three genes that in some pathogens encode enzymes that
      mask the LPS PAMP by upsetting the core-lipid A charge/hydrophobic balance.
      Brucella lptA, which encodes a putative ethanolamine transferase, carries a frame
      shift in B. abortus but not in other Brucella spp. and phylogenetic neighbors
      like the opportunistic pathogen Ochrobactrum anthropi. Consistent with the
      genomic evidence, a B. melitensis lptA mutant lacked lipid A-linked ethanolamine
      and displayed increased sensitivity to polymyxin B (a surrogate of innate
      immunity bactericidal peptides), while B. abortus carrying B. melitensis lptA
      displayed increased resistance. Brucella lpxE encodes a putative phosphatase
      acting on lipid A or on a free-lipid that is highly conserved in all brucellae
      and O. anthropi. Although we found no evidence of lipid A dephosphorylation, a B.
      abortus lpxE mutant showed increased polymyxin B sensitivity, suggesting the
      existence of a hitherto unidentified free-lipid involved in bactericidal peptide
      resistance. Gene lpxO putatively encoding an acyl hydroxylase carries a frame
      shift in all brucellae except B. microti and is intact in O. anthropi. Free-lipid
      analysis revealed that lpxO corresponded to olsC, the gene coding for the
      ornithine lipid (OL) acyl hydroxylase active in O. anthropi and B. microti, while
      B. abortus carrying the olsC of O. anthropi and B. microti synthesized
      hydroxylated OLs. Interestingly, mutants in lptA, lpxE, or olsC were not
      attenuated in dendritic cells or mice. This lack of an obvious effect on
      virulence together with the presence of the intact homolog genes in O. anthropi
      and B. microti but not in other brucellae suggests that LptA, LpxE, or OL beta
      hydroxylase do not significantly alter the PAMP properties of Brucella LPS and
      free-lipids and are therefore not positively selected during the adaptation to
      intracellular life.

PMID- 29375526
TI  - Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce
      Humoral and Cellular Immune Responses in Mice.
AB  - Ebola virus (EBOV) causes severe hemorrhagic fevers in humans, and no approved
      therapeutics or vaccine is currently available. Glycoprotein (GP) is the major
      protective antigen of EBOV, and can generate virus-like particles (VLPs) by co
      expression with matrix protein (VP40). In this study, we constructed a
      recombinant Alphavirus Semliki Forest virus (SFV) replicon vector DREP to express
      EBOV GP and matrix viral protein (VP40). EBOV VLPs were successfully generated
      and achieved budding from 293 cells after co-transfection with DREP-based GP and
      VP40 vectors (DREP-GP+DREP-VP40). Vaccination of BALB/c mice with DREP-GP, DREP
      VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation
      resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40
      proteins. This vaccination regimen also led to the generation of both Th1 and Th2
      cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP
      VP40, which produces both GP and VP40 antigens, induced a significantly higher
      level of anti-GP IgG2a antibody and increased IFN-gamma secreting CD8+ T-cell
      responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our
      study indicates that co-expression of GP and VP40 antigens based on the SFV
      replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant
      DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific
      humoral and cellular immune responses in mice. This novel approach provides a
      simple and efficient vaccine platform for Ebola disease prevention.

PMID- 29375525
TI  - Applications for Bacteriophage Therapy during Pregnancy and the Perinatal Period.
AB  - Pregnant women and their unborn children are a population that is particularly
      vulnerable to bacterial infection. Physiological changes that occur during
      pregnancy affect the way women respond to such infections and the options that
      clinicians have for treatment. Antibiotics are still considered the best option
      for active infections and a suitable prophylaxis for prevention of potential
      infections, such as vaginal/rectal Streptococcus agalactiae colonization prior to
      birth. The effect of such antibiotic use on the developing fetus, however, is
      still largely unknown. Recent research has suggested that the fetal gut
      microbiota plays a critical role in fetal immunologic programming. Hence, even
      minor alterations in this microbiota may have potentially significant downstream
      effects. An ideal antibacterial therapeutic for administration during pregnancy
      would be one that is highly specific for its target, leaving the surrounding
      microbiota intact. This review first provides a basic overview of the challenges
      a clinician faces when administering therapeutics to a pregnant patient and then
      goes on to explore common bacterial infections in pregnancy, use of antibiotics
      for treatment/prevention of such infections and the consequences of such
      treatment for the mother and infant. With this background established, the review
      then explores the potential for use of bacteriophage (phage) therapy as an
      alternative to antibiotics during the antenatal period. Many previous reviews
      have highlighted the revitalization of and potential for phage therapy for
      treatment of a range of bacterial infections, particularly in the context of the
      increasing threat of widespread antibiotic resistance. However, information on
      the potential for the use of phage therapeutics in pregnancy is lacking. This
      review aims to provide a thorough overview of studies of this nature and discuss
      the feasibility of bacteriophage use during pregnancy to treat and/or prevent
      bacterial infections.

PMID- 29375527
TI  - Exogenous Fecal Microbiota Transplantation from Local Adult Pigs to Crossbred
      Newborn Piglets.
AB  - This study was conducted to investigate the effect of exogenous fecal microbiota
      transplantation on gut bacterial community structure, gut barrier and growth
      performance in recipient piglets. Twelve litters of Duroc * Landrace * Yorkshire
      piglets of the same birth and parity were weighed and divided into two groups.
      One group (recipient piglets) was inoculated orally with fecal microbiota
      suspension of healthy adult Jinhua pigs daily from day 1 to day 11. The other
      (control) was given orally the same volume of sterile physiological saline at the
      same time. The experiment lasted 27 days. The results showed that the relative
      abundance of Firmicutes, Prevotellaceae, Lachnospiraceae, Ruminococcus,
      Prevotella, and Oscillospira in the colon of recipient piglets was increased.
      Proteobacteria, Fusobacteriaceae, Clostridiaceae, Pasteuriaceae, Alcaligenaceae,
      Bacteroidaceae, Veillonellaceae, Sutterella, Escherichia, and Bacteroides in the
      colon of recipient piglets were decreased. An average daily weight gain of
      recipient piglets was increased, and diarrhea incidence of the recipient was
      decreased during the trial. Intestinal morphology and tight junction barrier of
      recipient piglets were improved. The optical density of sIgA+ cells, the number
      of goblet cells and relative expressions of MUC2 in the intestinal mucosa of
      recipient piglets were enhanced. Protein expressions of beta-defensin 2 and mRNA
      expressions of TLR2 and TLR4 in the intestinal mucosa of recipient piglets were
      also increased. These findings supported that the exogenous fecal microbiota had
      significant effects on animal's growth performance, intestinal barrier function,
      and innate immune via modulating the composition of the gut microbiota.

PMID- 29375528
TI  - Tomato Apical Leaf Curl Virus: A Novel, Monopartite Geminivirus Detected in
      Tomatoes in Argentina.
AB  - Plant viruses that are members of the Geminiviridae family have circular single
      stranded DNA (ssDNA) genome and are responsible for major crop diseases
      worldwide. We have identified and characterized a novel monopartite geminivirus
      infecting tomato in Argentina. The full-length genome was cloned and sequenced.
      The genome-wide pairwise identity calculation that resulted in a maximum of 63%
      identity with all of other known geminiviruses indicated that it is a new
      geminivirus species. Biolistic infected plants presented interveinal yellowing,
      apical leaf curling and extreme root hypotrophy. Thus, the name proposed for this
      species is tomato apical leaf curl virus (ToALCV). The phylogenetic inferences
      suggested different evolutionary relationships for the replication-associated
      protein (Rep) and the coat protein (CP). Besides, the sequence similarity network
      (SSN) protein analyses showed that the complementary-sense gene products (RepA,
      Rep and C3) are similar to capulavirus while the viron-sense gene products (CP,
      MP and V3) are similar to topocuvirus, curtovirus and becurtovirus. Based on the
      data presented, ToALCV genome appears to have "modular organization" supported by
      its recombination origin. Analyses of the specificity-determining positions
      (SDPs) of the CP of geminiviruses defined nine subgroups that include
      geminiviruses that share the same type of insect vector. Our sequences were
      clustered with the sequences of topocuvirus, whose vector is the treehopper,
      Micrutalis malleifera. Also, a set of the highest scored amino acid residues was
      predicted for the CP, which could determine differences in virus transmission
      specificity. We predict that a treehopper could be the vector of ToALCV, but
      transmission assays need to be performed to confirm this. Given everything we
      demonstrate in this paper, ToALCV can be considered a type member of a new
      putative genus of the Geminiviridae family.

PMID- 29375529
TI  - Low Light Availability Alters Root Exudation and Reduces Putative Beneficial
      Microorganisms in Seagrass Roots.
AB  - Seagrass roots host a diverse microbiome that is critical for plant growth and
      health. Composition of microbial communities can be regulated in part by root
      exudates, but the specifics of these interactions in seagrass rhizospheres are
      still largely unknown. As light availability controls primary productivity,
      reduced light may impact root exudation and consequently the composition of the
      root microbiome. Hence, we analyzed the influence of light availability on root
      exudation and community structure of the root microbiome of three co-occurring
      seagrass species, Halophila ovalis, Halodule uninervis and Cymodocea serrulata.
      Plants were grown under four light treatments in mesocosms for 2 weeks; control
      (100% surface irradiance (SI), medium (40% SI), low (20% SI) and fluctuating
      light (10 days 20% and 4 days 100%). 16S rDNA amplicon sequencing revealed that
      microbial diversity, composition and predicted function were strongly influenced
      by the presence of seagrass roots, such that root microbiomes were unique to each
      seagrass species. Reduced light availability altered seagrass root exudation, as
      characterized using fluorescence spectroscopy, and altered the composition of
      seagrass root microbiomes with a reduction in abundance of potentially beneficial
      microorganisms. Overall, this study highlights the potential for above-ground
      light reduction to invoke a cascade of changes from alterations in root exudation
      to a reduction in putative beneficial microorganisms and, ultimately, confirms
      the importance of the seagrass root environment - a critical, but often
      overlooked space.

PMID- 29375530
TI  - Production of the Plant Hormone Auxin by Salmonella and Its Role in the
      Interactions with Plants and Animals.
AB  - The ability of human enteric pathogens to colonize plants and use them as
      alternate hosts is now well established. Salmonella, similarly to phytobacteria,
      appears to be capable of producing the plant hormone auxin via an indole-3
      pyruvate decarboxylase (IpdC), a key enzyme of the IPyA pathway. A deletion of
      the Salmonella ipdC significantly reduced auxin synthesis in laboratory culture.
      The Salmonella ipdC gene was expressed on root surfaces of Medicago truncatula.
      M. truncatula auxin-responsive GH3::GUS reporter was activated by the wild type
      Salmonella, and not but the ipdC mutant, implying that the bacterially produced
      IAA (Indole Acetic Acid) was detected by the seedlings. Seedling infections with
      the wild type Salmonella caused an increase in secondary root formation, which
      was not observed in the ipdC mutant. The wild type Salmonella cells were detected
      as aggregates at the sites of lateral root emergence, whereas the ipdC mutant
      cells were evenly distributed in the rhizosphere. However, both strains appeared
      to colonize seedlings well in growth pouch experiments. The ipdC mutant was also
      less virulent in a murine model of infection. When mice were infected by oral
      gavage, the ipdC mutant was as proficient as the wild type strain in colonization
      of the intestine, but it was defective in the ability to cross the intestinal
      barrier. Fewer cells of the ipdC mutant, compared with the wild type strain, were
      detected in Peyer's patches, spleen and in the liver. Orthologs of ipdC are found
      in all Salmonella genomes and are distributed among many animal pathogens and
      plant-associated bacteria of the Enterobacteriaceae, suggesting a broad
      ecological role of the IpdC-catalyzed pathway.

PMID- 29375531
TI  - Leaf-FISH: Microscale Imaging of Bacterial Taxa on Phyllosphere.
AB  - Molecular methods for microbial community characterization have uncovered
      environmental and plant-associated factors shaping phyllosphere communities.
      Variables undetectable using bulk methods can play an important role in shaping
      plant-microbe interactions. Microscale analysis of bacterial dynamics in the
      phyllosphere requires imaging techniques specially adapted to the high
      autoflouresence and 3-D structure of the leaf surface. We present an easily
      transferable method (Leaf-FISH) to generate high-resolution tridimensional images
      of leaf surfaces that allows simultaneous visualization of multiple bacterial
      taxa in a structurally informed context, using taxon-specific fluorescently
      labeled oligonucleotide probes. Using a combination of leaf pretreatments coupled
      with spectral imaging confocal microscopy, we demonstrate the successful imaging
      bacterial taxa at the genus level on cuticular and subcuticular leaf areas. Our
      results confirm that different bacterial species, including closely related
      isolates, colonize distinct microhabitats in the leaf. We demonstrate that highly
      related Methylobacterium species have distinct colonization patterns that could
      not be predicted by shared physiological traits, such as carbon source
      requirements or phytohormone production. High-resolution characterization of
      microbial colonization patterns is critical for an accurate understanding of
      microbe-microbe and microbe-plant interactions, and for the development of foliar
      bacteria as plant-protective agents.

PMID- 29375532
TI  - Composition and Functional Specialists of the Gut Microbiota of Frogs Reflect
      Habitat Differences and Agricultural Activity.
AB  - The physiological impact of agricultural pollution, habitat disturbance, and food
      source variability on amphibian remains poorly understood. By comparing the
      composition and predicted functions of gut microbiota of two frog species from
      forest and farmland, we quantified the effects of the exogenous environment and
      endogenous filters on gut microbiota and the corresponding functions. However,
      compositional differences of the gut microbiota between the frog species were not
      detected, even when removing roughly 80-88% of the confounding effect produced by
      common and shared bacteria (i.e., generalists) and those taxa deemed too rare.
      The habitat effect accounted for 14.1% of the compositional difference of gut
      microbial specialists, but host and host * habitat effects were not significant.
      Similar trends of a significant habitat effect, at an even higher level (26.0%),
      for the physiological and metabolic functions of gut microbiota was predicted. A
      very obvious skewing of the relative abundance of functional groups toward
      farmland habitats reflects the highly diverse bacterial functions of farmland
      frogs, in particular related to pathogenic disease and pesticide degradation,
      which may be indication of poor adaptation or strong selective pressure against
      disease. These patterns reflect the impacts of agricultural activities on frogs
      and how such stresses may be applied in an unequal manner for different frog
      species.

PMID- 29375534
TI  - Evolution of Yeast Consortia during the Fermentation of Kalamata Natural Black
      Olives upon Two Initial Acidification Treatments.
AB  - The objective of this study was to elucidate the yeast consortia structure and
      dynamics during Greek-style processing of Kalamata natural black olives in
      different brine solutions. Olives were subjected to spontaneous fermentation in
      7% (w/v) NaCl brine solution (control treatment) or brine acidified with (a) 0.5%
      (v/v) vinegar, and (b) 0.1% (v/v) lactic acid at the onset of fermentation.
      Changes in microbial counts, pH, acidity, organic acids, sugars, and alcohols
      were analyzed for a period of 187 days. Yeast consortia diversity was evaluated
      at days 4, 34, 90, 140, and 187 of fermentation. A total of 260 isolates were
      characterized at sub-species level by rep-PCR genomic fingerprinting with the
      oligo-nucleotide primer (GTG)5. The characterization of yeast isolates at species
      level was performed by sequencing of the D1/D2 domain of 26S rRNA gene. Results
      showed that yeasts dominated the process presenting a relatively broad range of
      biodiversity composed of 11 genera and 21 species. No lactic acid bacteria (LAB)
      or Enterobacteriaceae could be enumerated after 20 and 10 days of fermentation,
      respectively. The dominant yeast species at the beginning were Aureobasidium
      pullulans for control and vinegar acidification treatments, and Candida
      naeodendra for lactic acid treatment. Between 34 and 140 days the dominant
      species were Candida boidinii, Candida molendinolei and Saccharomyces cerevisiae.
      In the end of fermentation the dominant species in all processes were C. boidinii
      and C. molendinolei, followed by Pichia manshurica and S. cerevisiae in lactic
      acid acidification treatment, P. manshurica in vinegar acidification treatment,
      and Pichia membranifaciens in control fermentation.

PMID- 29375533
TI  - Surface Sensing for Biofilm Formation in Pseudomonas aeruginosa.
AB  - Aggregating and forming biofilms on biotic or abiotic surfaces are ubiquitous
      bacterial behaviors under various conditions. In clinical settings, persistent
      presence of biofilms increases the risks of healthcare-associated infections and
      imposes huge healthcare and economic burdens. Bacteria within biofilms are
      protected from external damage and attacks from the host immune system and can
      exchange genomic information including antibiotic-resistance genes. Dispersed
      bacterial cells from attached biofilms on medical devices or host tissues may
      also serve as the origin of further infections. Understanding how bacteria
      develop biofilms is pertinent to tackle biofilm-associated infections and
      transmission. Biofilms have been suggested as a continuum of growth modes for
      adapting to different environments, initiating from bacterial cells sensing their
      attachment to a surface and then switching cellular physiological status for
      mature biofilm development. It is crucial to understand bacterial gene regulatory
      networks and decision-making processes for biofilm formation upon initial surface
      attachment. Pseudomonas aeruginosa is one of the model microorganisms for
      studying bacterial population behaviors. Several hypotheses and studies have
      suggested that extracellular macromolecules and appendages play important roles
      in bacterial responses to the surface attachment. Here, I review recent studies
      on potential molecular mechanisms and signal transduction pathways for P.
      aeruginosa surface sensing.

PMID- 29375535
TI  - Comprehensive Proteomic Analysis of Lysine Acetylation in the Foodborne Pathogen
      Trichinella spiralis.
AB  - Lysine acetylation is a dynamic and highly conserved post-translational
      modification that plays a critical role in regulating diverse cellular processes.
      Trichinella spiralis is a foodborne parasite with a considerable socio-economic
      impact. However, to date, little is known regarding the role of lysine
      acetylation in this parasitic nematode. In this study, we utilized a proteomic
      approach involving anti-acetyl lysine-based enrichment and highly sensitive mass
      spectrometry to identify the global acetylated proteome and investigate lysine
      acetylation in T. spiralis. In total, 3872 lysine modification sites were
      identified in 1592 proteins that are involved in a wide variety of biological
      processes. Consistent with the results of previous studies, a large number of the
      acetylated proteins appear to be involved in metabolic and biosynthetic
      processes. Interestingly, according to the functional enrichment analysis, 29
      acetylated proteins were associated with phagocytosis, suggesting an important
      role of lysine acetylation in this process. Among the identified proteins, 15
      putative acetylation motifs were detected. The presence of serine downstream of
      the lysine acetylation site was commonly observed in the regions surrounding the
      sites. Moreover, protein interaction network analysis revealed that various
      interactions are regulated by protein acetylation. These data represent the first
      report of the acetylome of T. spiralis and provide an important resource for
      further explorations of the role of lysine acetylation in this foodborne
      pathogen.

PMID- 29375536
TI  - Transcriptional Modulation of Penicillin-Binding Protein 1b, Outer Membrane
      Protein P2 and Efflux Pump (AcrAB-TolC) during Heat Stress Is Correlated to
      Enhanced Bactericidal Action of Imipenem on Non-typeable Haemophilus influenzae.
AB  - Objective: The purpose of the present study was to investigate the penicillin
      binding proteins (PBPs), drug influx and efflux modulations during heat stress
      and their effects on the bactericidal action of imipenem on non-typeable
      Haemophilus influenzae (NTHi). Methods: The two NTHi clinical isolates (GE47 and
      GE88, imipenem MICs by E-test > 32 MUg/mL) examined in this study were collected
      at Geneva University Hospitals. The imipenem killing activity was assessed after
      incubation of the NTHi strains at either 37 or 42 degrees C for 3 h with
      increasing concentrations of imipenem. The detection of PBPs was carried out by
      Bocillin-FL. Global transcriptional changes were monitored by RNA-seq after pre
      incubation of bacterial cells at either 37 or 42 degrees C, and the expression
      levels of relevant target genes were confirmed by qRT-PCR. Results: Quantitation
      of NTHi viable cells after incubation with 0.25 MUg/mL of imipenem for 3 h
      revealed more than a twofold decrease in GE47 and GE88 viable cells at 42 degrees
      C as compared to 37 degrees C. Transcriptome analysis showed that under heat
      stress conditions, there were 141 differentially expressed genes with a |
      log2(fold change)| > 1, including 67 up-regulated and 74 down-regulated genes.
      The expression levels of ponB (encoding PBP1b) and acrR (regulator of AcrAB-TolC
      efflux pump) were significantly increased at 42 degrees C. In contrast, the
      transcript levels of ompP2 (encoding the outer membrane protein P2) and acrB gene
      (encoding AcrB) were significantly lower under heat stress condition. Conclusion:
      This study shows that the transcriptional modulation of ponB, ompP2, acrR, and
      acrB in the heat stress response is correlated to enhanced antimicrobial effects
      of imipenem on non-typeable H. influenzae.

PMID- 29375537
TI  - Overcoming Antimicrobial Resistance in Bacteria Using Bioactive Magnetic
      Nanoparticles and Pulsed Electromagnetic Fields.
AB  - Nisin is a known bacteriocin, which exhibits a wide spectrum of antimicrobial
      activity, while commonly being inefficient against Gram-negative bacteria. In
      this work, we present a proof of concept of novel antimicrobial methodology using
      targeted magnetic nisin-loaded nano-carriers [iron oxide nanoparticles (NPs) (11
      13 nm) capped with citric, ascorbic, and gallic acids], which are activated by
      high pulsed electric and electromagnetic fields allowing to overcome the nisin
      resistance of bacteria. As a cell model the Gram-positive bacteria Bacillus
      subtilis and Gram-negative Escherichia coli were used. We have applied 10 and 30
      kV cm-1 electric field pulses (100 MUs * 8) separately and in combination with
      two pulsed magnetic field protocols: (1) high dB/dt 3.3 T * 50 and (2) 10 mT, 100
      kHz, 2 min protocol to induce additional permeabilization and local magnetic
      hyperthermia. We have shown that the high dB/dt pulsed magnetic fields increase
      the antimicrobial efficiency of nisin NPs similar to electroporation or magnetic
      hyperthermia methods and a synergistic treatment is also possible. The results of
      our work are promising for the development of new methods for treatment of the
      drug-resistant foodborne pathogens to minimize the risks of invasive infections.

PMID- 29375538
TI  - Classical Swine Fever Virus Infection and Its NS4A Protein Expression Induce IL-8
      Production through MAVS Signaling Pathway in Swine Umbilical Vein Endothelial
      Cells.
AB  - Classical swine fever virus (CSFV) infection causes a severe disease of pigs,
      which is characterized by hemorrhage, disseminated intravascular coagulation, and
      leucopenia. IL-8, a main chemokine and activator of neutrophils, regulates the
      permeability of endothelium, which may be related to the hemorrhage upon CSFV
      infection. Until now, the molecular mechanisms of IL-8 regulation during CSFV
      infection are poorly defined. Here, we showed that CSFV infection induced IL-8
      production and the upregulation of IL-8 required virus replication in swine
      umbilical vein endothelial cells (SUVECs). Additionally, MAVS expression was
      increased and was required for IL-8 production upon CSFV infection. Moreover, ROS
      was involved in CSFV-induced IL-8 production. Subsequent studies demonstrated
      that ROS was involved in MAVS-induced IL-8 production and CSFV induced ROS
      production through MAVS pathway. These results indicate that CSFV induces IL-8
      production through MAVS pathway and production of ROS. The role of NS4A in the
      pathogenesis of CSFV is not well-understood. In this study, we further
      demonstrated that CSFV NS4A induced IL-8 production through enhancing MAVS
      pathway and promoted CSFV replication. In addition, we discovered that CSFV NS4A
      was localized in the cell nucleus and cytoplasm, including endoplasmic reticulum
      (ER) and mitochondria. Taken together, these results provide insights into the
      mechanisms of IL-8 regulation and NS4A functions during CSFV infection.

PMID- 29375539
TI  - Preliminary Comparison of Oral and Intestinal Human Microbiota in Patients with
      Colorectal Cancer: A Pilot Study.
AB  - In this study Next-Generation Sequencing (NGS) was used to analyze and compare
      human microbiota from three different compartments, i.e., saliva, feces, and
      cancer tissue (CT), of a selected cohort of 10 Italian patients with colorectal
      cancer (CRC) vs. 10 healthy controls (saliva and feces). Furthermore, the
      Fusobacterium nucleatum abundance in the same body site was investigated through
      real-time quantitative polymerase chain reaction (qPCR) to assess the association
      with CRC. Differences in bacterial composition, F. nucleatum abundance in healthy
      controls vs. CRC patients, and the association of F. nucleatum with clinical
      parameters were observed. Taxonomic analysis based on 16S rRNA gene, revealed the
      presence of three main bacterial phyla, which includes about 80% of reads:
      Firmicutes (39.18%), Bacteroidetes (30.36%), and Proteobacteria (10.65%). The
      results highlighted the presence of different bacterial compositions; in
      particular, the fecal samples of CRC patients seemed to be enriched with
      Bacteroidetes, whereas in the fecal samples of healthy controls Firmicutes were
      one of the major phyla detected though these differences were not statistically
      significant. The CT samples showed the highest alpha diversity values. These
      results emphasize a different taxonomic composition of feces from CRC compared to
      healthy controls. Despite the low number of samples included in the study, these
      results suggest the importance of microbiota in the CRC progression and could
      pave the way to the development of therapeutic interventions and novel microbial
      related diagnostic tools in CRC patients.

PMID- 29375540
TI  - Common Variable Immunodeficiency Non-Infectious Disease Endotypes Redefined Using
      Unbiased Network Clustering in Large Electronic Datasets.
AB  - Common variable immunodeficiency (CVID) is increasingly recognized for its
      association with autoimmune and inflammatory complications. Despite recent
      advances in immunophenotypic and genetic discovery, clinical care of CVID remains
      limited by our inability to accurately model risk for non-infectious disease
      development. Herein, we demonstrate the utility of unbiased network clustering as
      a novel method to analyze inter-relationships between non-infectious disease
      outcomes in CVID using databases at the United States Immunodeficiency Network
      (USIDNET), the centralized immunodeficiency registry of the United States, and
      Partners, a tertiary care network in Boston, MA, USA, with a shared electronic
      medical record amenable to natural language processing. Immunophenotypes were
      comparable in terms of native antibody deficiencies, low titer response to
      pneumococcus, and B cell maturation arrest. However, recorded non-infectious
      disease outcomes were more substantial in the Partners cohort across the spectrum
      of lymphoproliferation, cytopenias, autoimmunity, atopy, and malignancy. Using
      unbiased network clustering to analyze 34 non-infectious disease outcomes in the
      Partners cohort, we further identified unique patterns of lymphoproliferative
      (two clusters), autoimmune (two clusters), and atopic (one cluster) disease that
      were defined as CVID non-infectious endotypes according to discrete and non
      overlapping immunophenotypes. Markers were both previously described {high serum
      IgE in the atopic cluster [odds ratio (OR) 6.5] and low class-switched memory B
      cells in the total lymphoproliferative cluster (OR 9.2)} and novel [low serum C3
      in the total lymphoproliferative cluster (OR 5.1)]. Mortality risk in the
      Partners cohort was significantly associated with individual non-infectious
      disease outcomes as well as lymphoproliferative cluster 2, specifically (OR 5.9).
      In contrast, unbiased network clustering failed to associate known comorbidities
      in the adult USIDNET cohort. Together, these data suggest that unbiased network
      clustering can be used in CVID to redefine non-infectious disease inter
      relationships; however, applicability may be limited to datasets well annotated
      through mechanisms such as natural language processing. The lymphoproliferative,
      autoimmune, and atopic Partners CVID endotypes herein described can be used
      moving forward to streamline genetic and biomarker discovery and to facilitate
      early screening and intervention in CVID patients at highest risk for autoimmune
      and inflammatory progression.

PMID- 29375541
TI  - Metabolic Regulation of Innate Lymphoid Cell-Mediated Tissue Protection-Linking
      the Nutritional State to Barrier Immunity.
AB  - Innate lymphoid cells (ILC) are a recently described group of tissue-resident
      immune cells that play essential roles in maintaining and protecting the tissue
      barrier against invading pathogens. Extensive research has revealed that ILC
      mediated immune responses are controlled by dietary components and metabolites.
      An additional role of ILC as important direct regulators of host metabolism and
      glucose tolerance is emerging. This suggests that ILC may act as key dietary
      sensors integrating nutritional and metabolic stress to facilitate both
      maintenance of barrier sites and a coordinated immune response protecting these
      tissues. In this respect, investigations have begun to determine how different
      ILC responses are metabolically fueled and the impact of nutrient availability on
      the regulation of ILC function. Here, we discuss the current literature
      concerning dietary and metabolic control of ILC. In particular, we address
      whether the dietary and metabolic control of ILC and their simultaneous influence
      on host metabolism may function as a coordinated program of barrier defense.

PMID- 29375542
TI  - Stability-Diversity Tradeoffs Impose Fundamental Constraints on Selection of
      Synthetic Human VH/VL Single-Domain Antibodies from In Vitro Display Libraries.
AB  - Human autonomous VH/VL single-domain antibodies (sdAbs) are attractive
      therapeutic molecules, but often suffer from suboptimal stability, solubility and
      affinity for cognate antigens. Most commonly, human sdAbs have been isolated from
      in vitro display libraries constructed via synthetic randomization of rearranged
      VH/VL domains. Here, we describe the design and characterization of three novel
      human VH/VL sdAb libraries through a process of: (i) exhaustive biophysical
      characterization of 20 potential VH/VL sdAb library scaffolds, including
      assessment of expression yield, aggregation resistance, thermostability and
      tolerance to complementarity-determining region (CDR) substitutions; (ii) in
      vitro randomization of the CDRs of three VH/VL sdAb scaffolds, with tailored
      amino acid representation designed to promote solubility and expressibility; and
      (iii) systematic benchmarking of the three VH/VL libraries by panning against
      five model antigens. We isolated >=1 antigen-specific human sdAb against four of
      five targets (13 VHs and 7 VLs in total); these were predominantly monomeric, had
      antigen-binding affinities ranging from 5 nM to 12 uM (average: 2-3 uM), but had
      highly variable expression yields (range: 0.1-19 mg/L). Despite our efforts to
      identify the most stable VH/VL scaffolds, selection of antigen-specific binders
      from these libraries was unpredictable (overall success rate for all library
      target screens: ~53%) with a high attrition rate of sdAbs exhibiting false
      positive binding by ELISA. By analyzing VH/VL sdAb library sequence composition
      following selection for monomeric antibody expression (binding to protein A/L
      followed by amplification in bacterial cells), we found that some VH/VL sdAbs had
      marked growth advantages over others, and that the amino acid composition of the
      CDRs of this set of sdAbs was dramatically restricted (bias toward Asp and His
      and away from aromatic and hydrophobic residues). Thus, CDR sequence clearly
      dramatically impacts the stability of human autonomous VH/VL immunoglobulin
      domain folds, and sequence-stability tradeoffs must be taken into account during
      the design of such libraries.

PMID- 29375544
TI  - Nanoporous Microneedle Arrays Effectively Induce Antibody Responses against
      Diphtheria and Tetanus Toxoid.
AB  - The skin is immunologically very potent because of the high number of antigen
      presenting cells in the dermis and epidermis, and is therefore considered to be
      very suitable for vaccination. However, the skin's physical barrier, the stratum
      corneum, prevents foreign substances, including vaccines, from entering the skin.
      Microneedles, which are needle-like structures with dimensions in the micrometer
      range, form a relatively new approach to circumvent the stratum corneum, allowing
      for minimally invasive and pain-free vaccination. In this study, we tested
      ceramic nanoporous microneedle arrays (npMNAs), representing a novel microneedle
      based drug delivery technology, for their ability to deliver the subunit vaccines
      diphtheria toxoid (DT) and tetanus toxoid (TT) intradermally. First, the piercing
      ability of the ceramic (alumina) npMNAs, which contained over 100 microneedles
      per array, a length of 475 um, and an average pore size of 80 nm, was evaluated
      in mouse skin. Then, the hydrodynamic diameters of DT and TT and the loading of
      DT, TT, and imiquimod into, and subsequent release from the npMNAs were assessed
      in vitro. It was shown that DT and TT were successfully loaded into the tips of
      the ceramic nanoporous microneedles, and by using near-infrared fluorescently
      labeled antigens, we found that DT and TT were released following piercing of the
      antigen-loaded npMNAs into ex vivo murine skin. Finally, the application of DT-
      and TT-loaded npMNAs onto mouse skin in vivo led to the induction of antigen
      specific antibodies, with titers similar to those obtained upon subcutaneous
      immunization with a similar dose. In conclusion, we show for the first time, the
      potential of npMNAs for intradermal (ID) immunization with subunit vaccines,
      which opens possibilities for future ID vaccination designs.

PMID- 29375543
TI  - Tolerance through Education: How Tolerogenic Dendritic Cells Shape Immunity.
AB  - Dendritic cells (DCs) are central players in the initiation and control of
      responses, regulating the balance between tolerance and immunity. Tolerogenic DCs
      are essential in the maintenance of central and peripheral tolerance by induction
      of clonal T cell deletion and T cell anergy, inhibition of memory and effector T
      cell responses, and generation and activation of regulatory T cells. Therefore,
      tolerogenic DCs are promising candidates for specific cellular therapy of
      allergic and autoimmune diseases and for treatment of transplant rejection.
      Studies performed in rodents have demonstrated the efficacy and feasibility of
      tolerogenic DCs for tolerance induction in various inflammatory diseases. In the
      last years, numerous protocols for the generation of human monocyte-derived
      tolerogenic DCs have been established and some first phase I trials have been
      conducted in patients suffering from autoimmune disorders, demonstrating the
      safety and efficiency of this cell-based immunotherapy. This review gives an
      overview about methods and protocols for the generation of human tolerogenic DCs
      and their mechanisms of tolerance induction with the focus on interleukin-10
      modulated DCs. In addition, we will discuss the prerequisites for optimal
      clinical grade tolerogenic DC subsets and results of clinical trials with
      tolerogenic DCs in autoimmune diseases.

PMID- 29375545
TI  - Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control
      Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory
      Responses.
AB  - Apoptosis is a physiological cell death process essential for development, tissue
      homeostasis, and for immune defense of multicellular animals. Inhibitors of
      apoptosis proteins (IAPs) regulate apoptosis in response to various cellular
      assaults. Using both genetic and pharmacological approaches we demonstrate here
      that the IAPs not only support opportunistic survival of intracellular human
      pathogens like Chlamydia pneumoniae but also control plasticity of iNOS+ M1
      macrophage during the course of infection and render them refractory for immune
      stimulation. Treatment of Th1 primed macrophages with birinapant (IAP-specific
      antagonist) inhibited NO generation and relevant proteins involved in innate
      immune signaling. Accordingly, birinapant promoted hypoxia, angiogenesis, and
      tumor-induced M2 polarization of iNOS+ M1 macrophages. Interestingly, birinapant
      driven changes in immune signaling were accompanied with changes in the
      expression of various proteins involved in the metabolism, and thus revealing the
      new role of IAPs in immune metabolic reprogramming in committed macrophages.
      Taken together, our study reveals the significance of IAP targeting approaches
      (Smac mimetic compounds) for the management of infectious and inflammatory
      diseases relying on macrophage plasticity.

PMID- 29375546
TI  - Cu,Zn Superoxide Dismutase Genes in Tribolium castaneum: Evolution, Molecular
      Characterisation, and Gene Expression during Immune Priming.
AB  - The production of reactive oxygen species (ROS) is a normal consequence of the
      aerobic cell metabolism. Despite their high and potentially detrimental
      reactivity with various biomolecules, the endogenous production of ROS is a vital
      part of physiological, immunological, and molecular processes that contribute to
      fitness. The role of ROS in host-parasite interactions is frequently defined by
      their contribution to innate immunity as effectors, promoting parasite death
      during infections. In vertebrates, ROS and antioxidant system enzymes, such as
      superoxide dismutase (SOD) are also involved in acquired immune memory, where
      they are responsible for T-cell signalling, activation, proliferation, and
      viability. Based on recent findings, ROS are now also assumed to play a role in
      immune priming, i.e., a form of memory in invertebrates. In this study, the
      potential involvement of Cu,Zn SODs in immunity of the red flour beetle Tribolium
      castaneum is described for the first time, applying an approach that combines an
      in silico gene characterisation with an in vivo immune priming experiment using
      the Gram-positive entomopathogen Bacillus thuringiensis. We identified an
      unusually high number of three different transcripts for extracellular SOD and
      found that priming leads to a fine-tuned modulation of SOD expression,
      highlighting the potential of physiological co-adaptations for immune phenotypes.

PMID- 29375547
TI  - An Activating Janus Kinase-3 Mutation Is Associated with Cytotoxic T Lymphocyte
      Antigen-4-Dependent Immune Dysregulation Syndrome.
AB  - Heterozygous mutations in the cytotoxic T lymphocyte antigen-4 (CTLA-4) are
      associated with lymphadenopathy, autoimmunity, immune dysregulation, and
      hypogammaglobulinemia in about 70% of the carriers. So far, the incomplete
      penetrance of CTLA-4 haploinsufficiency has been attributed to unknown genetic
      modifiers, epigenetic changes, or environmental effects. We sought to identify
      potential genetic modifiers in a family with differential clinical penetrance of
      CTLA-4 haploinsufficiency. Here, we report on a rare heterozygous gain-of
      function mutation in Janus kinase-3 (JAK3) (p.R840C), which is associated with
      the clinical manifestation of CTLA-4 haploinsufficiency in a patient carrying a
      novel loss-of-function mutation in CTLA-4 (p.Y139C). While the asymptomatic
      parents carry either the CTLA-4 mutation or the JAK3 variant, their son has
      inherited both heterozygous mutations and suffers from hypogammaglobulinemia
      combined with autoimmunity and lymphoid hyperplasia. Although the patient's lymph
      node and spleen contained many hyperplastic germinal centers with follicular
      helper T (TFH) cells and immunoglobulin (Ig) G-positive B cells, plasma cell, and
      memory B cell development was impaired. CXCR5+PD-1+TIGIT+ TFH cells contributed
      to a large part of circulating T cells, but they produced only very low amounts
      of interleukin (IL)-4, IL-10, and IL-21 required for the development of memory B
      cells and plasma cells. We, therefore, suggest that the combination of the loss
      of-function mutation in CTLA-4 with the gain-of-function mutation in JAK3 directs
      the differentiation of CD4 T cells into dysfunctional TFH cells supporting the
      development of lymphadenopathy, hypogammaglobulinemia, and immunodeficiency.
      Thus, the combination of rare genetic heterozygous variants that remain
      clinically unnoticed individually may lead to T cell hyperactivity, impaired
      memory B cell, and plasma cell development resulting finally in combined
      immunodeficiency.

PMID- 29375548
TI  - Elevated Mitochondrial Reactive Oxygen Species and Cellular Redox Imbalance in
      Human NADPH-Oxidase-Deficient Phagocytes.
AB  - Chronic granulomatous disease (CGD) is caused by mutations in genes that encode
      the NADPH-oxidase and result in a failure of phagocytic cells to produce reactive
      oxygen species (ROS) via this enzyme system. Patients with CGD are highly
      susceptible to infections and often suffer from inflammatory disorders; the
      latter occurs in the absence of infection and correlates with the spontaneous
      production of inflammatory cytokines. This clinical feature suggests that NADPH
      oxidase-derived ROS are not required for, or may even suppress, inflammatory
      processes. Experimental evidence, however, implies that ROS are in fact required
      for inflammatory cytokine production. By using a myeloid cell line devoid of a
      functional NADPH-oxidase and primary CGD cells, we analyzed intracellular
      oxidants, signs of oxidative stress, and inflammatory cytokine production.
      Herein, we demonstrate that phagocytes lacking a functional NADPH-oxidase, namely
      primary CGD phagocytes and a gp91phox-deficient cell line, display elevated
      levels of ROS derived from mitochondria. Accordingly, these cells, despite
      lacking the major source of cellular ROS, display clear signs of oxidative
      stress, including an induced expression of antioxidants and altered oxidation of
      cell surface thiols. These observed changes in redox state were not due to
      abnormalities in mitochondrial mass or membrane integrity. Finally, we
      demonstrate that increased mitochondrial ROS enhanced phosphorylation of ERK1/2,
      and induced production of IL8, findings that correlate with previous observations
      of increased MAPK activation and inflammatory cytokine production in CGD cells.
      Our data show that elevated baseline levels of mitochondria-derived oxidants lead
      to the counter-intuitive observation that CGD phagocytes are under oxidative
      stress and have enhanced MAPK signaling, which may contribute to the elevated
      basal production of inflammatory cytokines and the sterile inflammatory
      manifestations in CGD.

PMID- 29375550
TI  - Alkaline pH Promotes NADPH Oxidase-Independent Neutrophil Extracellular Trap
      Formation: A Matter of Mitochondrial Reactive Oxygen Species Generation and
      Citrullination and Cleavage of Histone.
AB  - pH is highly variable in different tissues and affects many enzymatic reactions
      in neutrophils. In response to calcium ionophores such as A23187 and ionomycin,
      neutrophils undergo nicotinamide adenine dinucleotide phosphate oxidase (NOX)
      independent neutrophil extracellular trap (NET) formation (NETosis). However, how
      pH influences calcium-dependent Nox-independent NET formation is not well
      understood. We hypothesized that increasing pH promotes Nox-independent NET
      formation by promoting calcium influx, mitochondrial reactive oxygen species
      (mROS) generation, histone citrullination, and histone cleavage. Here, we show
      that stimulating human neutrophils isolated from peripheral blood with calcium
      ionophore A23187 or ionomycin in the media with increasing extracellular pH (6.6,
      6.8, 7.0, 7.2, 7.4, 7.8) drastically increases intracellular pH within in 10-20
      min. These intracellular pH values are much higher compared to unstimulated cells
      placed in the media with corresponding pH values. Raising pH slightly drastically
      increases intracellular calcium concentration in resting and stimulated
      neutrophils, respectively. Like calcium, mROS generation also increases with
      increasing pH. An mROS scavenger, MitoTempo, significantly suppresses calcium
      ionophore-mediated NET formation with a greater effect at higher pH, indicating
      that mROS production is at least partly responsible for pH-dependent suppression
      of Nox-independent NETosis. In addition, raising pH increases PAD4 activity as
      determined by the citrullination of histone (CitH3) and histone cleavage
      determined by Western blots. The pH-dependent histone cleavage is reproducibly
      very high during ionomycin-induced NETosis compared to A23187-induced NETosis.
      Little or no histone cleavage was noted in unstimulated cells, at any pH. Both
      CitH3 and cleavage of histones facilitate DNA decondensation. Therefore, alkaline
      pH promotes intracellular calcium influx, mROS generation, PAD4-mediated CitH3
      formation, histone 4 cleavage and eventually NET formation. Calcium-mediated NET
      formation and CitH3 formation are often related to sterile inflammation. Hence,
      understanding these important mechanistic steps helps to explain how pH regulates
      NOX-independent NET formation, and modifying pH may help to regulate NET
      formation during sterile inflammation or potential damage caused by compounds
      such as ionomycin, secreted by Streptomyces, a group of Gram-positive bacteria
      well known for producing antibiotics.

PMID- 29375552
TI  - Chronic Active Epstein-Barr Virus Disease.
AB  - Chronic active Epstein-Barr virus (CAEBV) disease is a rare disorder in which
      persons are unable to control infection with the virus. The disease is
      progressive with markedly elevated levels of EBV DNA in the blood and
      infiltration of organs by EBV-positive lymphocytes. Patients often present with
      fever, lymphadenopathy, splenomegaly, EBV hepatitis, or pancytopenia. Over time,
      these patients develop progressive immunodeficiency and if not treated, succumb
      to opportunistic infections, hemophagocytosis, multiorgan failure, or EBV
      positive lymphomas. Patients with CAEBV in the United States most often present
      with disease involving B or T cells, while in Asia, the disease usually involves
      T or NK cells. The only proven effective treatment for the disease is
      hematopoietic stem cell transplantation. Current studies to find a cause of this
      disease focus on immune defects and genetic abnormalities associated with the
      disease.

PMID- 29375551
TI  - Engineering of Fc Fragments with Optimized Physicochemical Properties Implying
      Improvement of Clinical Potentials for Fc-Based Therapeutics.
AB  - Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in
      treatment of various diseases mainly including cancer, immune disease, and viral
      infection, which belong to the Fc-based therapeutics. In recent years, engineered
      Fc-derived antibody domains have also shown potential for Fc-based therapeutics.
      To increase the druggability of Fc-based therapeutic candidates, many efforts
      have been made in optimizing physicochemical properties and functions mediated by
      Fc fragment. The desired result is that we can simultaneously obtain Fc variants
      with increased physicochemical properties in vitro and capacity of mediating
      appropriate functions in vivo. However, changes of physicochemical properties of
      Fc may result in alternation of Fc-mediated functions and vice versa, which leads
      to undesired outcomes for further development of Fc-based therapeutics.
      Therefore, whether modified Fc fragments are suitable for achievement of expected
      clinical results or not needs to be seriously considered. Now, this question
      comes to be noticed and should be figured out to make better translation from the
      results of laboratory into clinical applications. In this review, we summarize
      different strategies on engineering physicochemical properties of Fc, and
      preliminarily elucidate the relationships between modified Fc in vitro and the
      subsequent therapeutic influence in vivo.

PMID- 29375553
TI  - GATA2 Deficiency and Epstein-Barr Virus Disease.
AB  - GATA2 is a transcription factor that binds to the promoter of hematopoietic
      genes. Mutations in one copy of the gene are associated with haploinsufficiency
      and reduced levels of protein. This results in reduced numbers of several cell
      types important for immune surveillance including dendritic cells, monocytes,
      CD4, and NK cells, as well as impaired NK cell function. Recently, GATA2 has been
      associated with several different presentations of severe Epstein-Barr virus
      (EBV) disease including primary infection requiring repeated hospitalizations,
      chronic active EBV disease, EBV-associated hydroa vacciniforme with
      hemophagocytosis, and EBV-positive smooth muscle tumors. EBV was found
      predominantly in B cells in each of the cases in which it was studied, unlike
      most cases of chronic active EBV disease in which the virus is usually present in
      T or NK cells. The variety of EBV-associated diseases seen in patients with GATA2
      deficiency suggest that additional forms of severe EBV disease may be found in
      patients with GATA2 deficiency in the future.

PMID- 29375554
TI  - Expression of Membrane-Bound CC Chemokine Ligand 20 on Follicular T Helper Cells
      in T-B-Cell Conjugates.
AB  - The CC chemokine receptor 6 (CCR6) and its sole chemokine ligand CC chemokine
      ligand 20 (CCL20) display an emerging role in the coordination of humoral immune
      responses. Recent studies demonstrate a role of this chemokine axis in the
      migration of B cells to key immunological sites during an immune response, and
      facilitating the generation of high-quality antibodies. Very little, however, is
      known about CCL20 and its role in these functions. We undertook a preliminary
      investigation into the expression and function of CCL20 and demonstrate its well
      noted upregulation in the spleen during immunization. Furthermore, we show that
      most follicular T helper (Tfh) cells can be CCR6+ and can produce CCL20.
      Surprisingly, CCL20 cannot only be found in the cytoplasm but also on the surface
      of these cells and their precursors. Analysis of T-B-cell conjugates revealed
      that mature Tfh cells, but not their precursors, are highly enriched in the
      conjugates. Further functional studies are needed to unravel the precise role of
      CCL20 in coordinating T and B cell interactions during the humoral immune
      response.

PMID- 29375555
TI  - Genomic Region Containing Toll-Like Receptor Genes Has a Major Impact on Total
      IgM Antibodies Including KLH-Binding IgM Natural Antibodies in Chickens.
AB  - Natural antibodies (NAb) are antigen binding antibodies present in individuals
      without a previous exposure to this antigen. Keyhole limpet hemocyanin (KLH)
      binding NAb levels were previously associated with survival in chickens. This
      suggests that selective breeding for KLH-binding NAb may increase survival by
      means of improved general disease resistance. Genome-wide association studies
      (GWAS) were performed to identify genes underlying genetic variation in NAb
      levels. The studied population consisted of 1,628 adolescent layer chickens with
      observations for titers of KLH-binding NAb of the isotypes IgM, IgA, IgG, the
      total KLH-binding (IgT) NAb titers, total antibody concentrations of the isotypes
      IgM, IgA, IgG, and the total antibodies concentration in plasma. GWAS were
      performed using 57,636 single-nucleotide polymorphisms (SNP). One chromosomal
      region on chromosome 4 was associated with KLH-binding IgT NAb, and total IgM
      concentration, and especially with KLH-binding IgM NAb. The region of interest
      was fine mapped by imputing the region of the study population to whole genome
      sequence, and subsequently performing an association study using the imputed
      sequence variants. 16 candidate genes were identified, of which FAM114A1, Toll
      like receptor 1 family member B (TLR1B), TLR1A, Kruppel-like factor 3 (KLF3)
      showed the strongest associations. SNP located in coding regions of the candidate
      genes were checked for predicted changes in protein functioning. One SNP (at
      69,965,939 base pairs) received the maximum impact score from two independent
      prediction tools, which makes this SNP the most likely causal variant. This SNP
      is located in TLR1A, which suggests a fundamental role of TLR1A on regulation of
      IgM levels (i.e., KLH-binding IgM NAb, and total IgM concentration), or B cells
      biology, or both. This study contributes to increased understanding of (genetic)
      regulation of KLH-binding NAb levels, and total antibody concentrations.

PMID- 29375549
TI  - Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome.
AB  - Bronchiolitis obliterans syndrome (BOS), the main manifestation of chronic lung
      allograft dysfunction, leads to poor long-term survival after lung
      transplantation. Identifying predictors of BOS is essential to prevent the
      progression of dysfunction before irreversible damage occurs. By using a large
      set of 107 samples from lung recipients, we performed microarray gene expression
      profiling of whole blood to identify early biomarkers of BOS, including samples
      from 49 patients with stable function for at least 3 years, 32 samples collected
      at least 6 months before BOS diagnosis (prediction group), and 26 samples at or
      after BOS diagnosis (diagnosis group). An independent set from 25 lung recipients
      was used for validation by quantitative PCR (13 stables, 11 in the prediction
      group, and 8 in the diagnosis group). We identified 50 transcripts differentially
      expressed between stable and BOS recipients. Three genes, namely POU class 2
      associating factor 1 (POU2AF1), T-cell leukemia/lymphoma protein 1A (TCL1A), and
      B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more
      than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and
      0.78 respectively. These genes allow stratification based on BOS risk (log-rank
      test p < 0.01) and are not associated with time posttransplantation. This is the
      first published large-scale gene expression analysis of blood after lung
      transplantation. The three-gene blood signature could provide clinicians with new
      tools to improve follow-up and adapt treatment of patients likely to develop BOS.

PMID- 29375558
TI  - Editorial: CD4 T Follicular Helper Cells in HIV.

PMID- 29375556
TI  - A Phase 2a Randomized Study to Evaluate the Safety and Immunogenicity of the
      1790GAHB Generalized Modules for Membrane Antigen Vaccine against Shigella sonnei
      Administered Intramuscularly to Adults from a Shigellosis-Endemic Country.
AB  - Shigellosis is a mild-to-severe diarrheal infection, caused by the genus
      Shigella, and is responsible for significant morbidity and mortality worldwide.
      We evaluated the safety and immunogenicity of an investigational Shigella sonnei
      vaccine (1790GAHB) based on generalized modules for membrane antigens (GMMA) in
      Kenya, a Shigella-endemic country. This phase 2a, observer-blind, controlled
      randomized study (NCT02676895) enrolled 74 healthy adults aged 18-45 years, of
      whom 72 were vaccinated. Participants received, in a 1:1:1 ratio, two
      vaccinations with the 1790GAHB vaccine at doses of either 1.5/25 MUg of O antigen
      (OAg)/protein (group 1.5/25 MUg) or 5.9/100 MUg (group 5.9/100 MUg) at day (D) 1
      and D29, or vaccination with a quadrivalent meningococcal vaccine at D1 and
      tetanus, diphtheria, and acellular pertussis vaccine at D29 (control group).
      Solicited and unsolicited adverse events (AEs), serious AEs (SAEs), and AEs of
      special interest (neutropenia and reactive arthritis) were collected. Anti-S.
      sonnei lipopolysaccharide (LPS) serum immunoglobulin G (IgG) geometric mean
      concentrations (GMC) were evaluated at D1, D29, and D57 and compared to anti-S.
      sonnei LPS antibody levels in convalescent patients naturally exposed to S.
      sonnei. The percentages of participants with seroresponse were also calculated.
      The most frequently reported solicited local and systemic AEs across all groups
      were pain and headache, respectively. Only one case of severe systemic reaction
      was reported (severe headache after first vaccination in group 5.9/100 MUg).
      Seven and three episodes of neutropenia, assessed as probably or possibly related
      to vaccination respectively, were reported in the investigational and control
      groups, respectively. No other SAEs were reported. Despite very high baseline
      anti-S. sonnei LPS serum IgG levels, the 1790GAHB vaccine induced robust antibody
      responses. At D29, GMC increased 2.10- and 4.43-fold from baseline in groups
      1.5/25 and 5.9/100 MUg, respectively, whereas no increase was observed in the
      control group. Antibody titers at D57 were not statistically different from those
      at D29. Seroresponse was 68% at D29 and 90% at D57 in group 1.5/25 MUg, and 96%
      after each vaccination in group 5.9/100 MUg. The 1790GAHB vaccine was well
      tolerated and highly immunogenic in a population of African adults, regardless of
      the GMMA OAg/protein content used.

PMID- 29375557
TI  - Antibiotic-Induced Pathobiont Dissemination Accelerates Mortality in Severe
      Experimental Pancreatitis.
AB  - Although antibiotic-induced dysbiosis has been demonstrated to exacerbate
      intestinal inflammation, it has been suggested that antibiotic prophylaxis may be
      beneficial in certain clinical conditions such as acute pancreatitis (AP).
      However, whether broad-spectrum antibiotics, such as meropenem, influence the
      dissemination of multidrug-resistant (MDR) bacteria during severe AP has not been
      addressed. In the currently study, a mouse model of obstructive severe AP was
      employed to investigate the effects of pretreatment with meropenem on bacteria
      spreading and disease outcome. As expected, animals subjected to biliopancreatic
      duct obstruction developed severe AP. Surprisingly, pretreatment with meropenem
      accelerated the mortality of AP mice (survival median of 2 days) when compared to
      saline-pretreated AP mice (survival median of 7 days). Early mortality was
      associated with the translocation of MDR strains, mainly Enterococcus gallinarum
      into the blood stream. Induction of AP in mice with guts that were enriched with
      E. gallinarum recapitulated the increased mortality rate observed in the
      meropenem-pretreated AP mice. Furthermore, naive mice challenged with a mouse or
      a clinical strain of E. gallinarum succumbed to infection through a mechanism
      involving toll-like receptor-2. These results confirm that broad-spectrum
      antibiotics may lead to indirect detrimental effects during inflammatory disease
      and reveal an intestinal pathobiont that is associated with the meropenem
      pretreatment during obstructive AP in mice.

PMID- 29375559
TI  - The Different Functional Distribution of "Not Effector" T Cells (Treg/Tnull) in
      Colorectal Cancer.
AB  - Colorectal cancer (CRC) is the third most common cancer worldwide, ranking as
      high as the second leading cause of cancer-related deaths in industrialized
      countries. Consistent with immunosurveillance theory, the immune system is
      crucial to protect the host from developing tumors, and the major players in
      tumoral immunity are effector T cells. Anyway, cancer cells develop strategies of
      immunoevasion influencing the cancer-specific lymphocyte priming, activation, and
      effector function. Therefore, the T cell subsets that mature during the stages of
      tumor growth, differently contribute to disease progression and/or regression. In
      our study, we analyzed the intra-tumoral and peripheral T cell subsets'
      distribution in 30 patients with CRC, in order to clarify their functional role
      toward cancer. We found that percentage of infiltrating effector T cells
      decreased in cancer tissue than in healthy mucosa and that the tumor
      microenvironment negatively influences the cytolytic activity of T lymphocytes
      reactive to cancer cells. Moreover, we found that the tumor tissue was
      infiltrated by a large amount of "not effector" T (neT) cells with a regulatory
      or an anergic profile, which are unable to kill cancer cells, may be contributing
      to the CRC promotion. The presence of neT cells was investigated also in the
      peripheral blood of CRC patients, demonstrating that the peripheral T regulatory
      cells can inhibit the proliferation of effector T cells, confirming their
      immunosuppressive properties. Finally, monitoring the changes in circulating neT
      cells' frequencies after the tumor removal, we confirmed the role of cancer in
      the modulation of immune system, in particular, in supporting a Tregs-mediated
      immunosuppression.

PMID- 29375560
TI  - Excess of Mortality in Adults and Elderly and Circulation of Subtypes of
      Influenza Virus in Southern Brazil.
AB  - Purpose: In the elderly population, the influenza infection and its clinical
      complications are important causes of hospitalization and death, particularly, in
      longer-lived age. The objective of this study is to analyze the impact of
      influenza virus circulation on mortality in the elderly and adults, in years with
      different predominant virus strains. Methods: We performed a time trend study to
      evaluated excess of mortality for pneumonia and influenza, respiratory disease,
      and all-causes in southern region of Brazil, from 2002 to 2015. After considering
      other models, we opted for Serfling regression. Excess of death rates per 100,000
      inhabitants were analyzed in specific age groups (24-59, 60-69, 70-79, >=80
      years) and by year of occurrence. Mortality information were taken from Brazilian
      Mortality Information System and etiological data were accessed in Sentinel
      Virological Surveillance database, getting the weekly positivity of the
      immunofluorescence tests for influenza A (H1N1, H3N2), and B. Results: In
      southern Brazil, there is an evident seasonal pattern of all death outcomes among
      different age groups in the dry and cold season (April-September). The highest
      excess mortality rates occurs among older, particularly in years of circulation
      of influenza AH3N2, especially among people >=80 years, in 2003 and 2007-years of
      great severity of influenza activity. After 2009, with the introduction of the
      pandemic influenza AH1N1, we observed a lower impact on the mortality of the
      elderly compared to <60 years. Discussion: A cross reactivity antibody response
      from past exposure probably provided protection against disease in the elderly.
      Despite not controlling for comorbidities, climate, and vaccination, for the >70
      years, ratio of respiratory diseases excess mortality rates between AH1N1 (2009)
      and severe year of H3N2 (2007) shows protection in the pandemic year and great
      vulnerability during AH3N2 virus predominance. Conclusion: The reduced immune
      response to infection, and to vaccination, and presence of comorbidities
      recommend a special attention to this age group in Brazil. Besides medical
      assistance, the timeliness of vaccine campaigns, its composition, and etiological
      surveillance of respiratory diseases are some of the preventive and public health
      measures.

PMID- 29375562
TI  - Simultaneous Ablation of Uterine Natural Killer Cells and Uterine Mast Cells in
      Mice Leads to Poor Vascularization and Abnormal Doppler Measurements That
      Compromise Fetal Well-being.
AB  - Intrauterine growth restriction (IUGR) is a serious pregnancy complication with
      short- and long-term health consequences. The mechanisms underlying this
      condition are not well understood. Animal models are the basis for understanding
      the causes of IUGR and for developing useful therapeutic strategies. Here, we
      aimed to ascertain the in utero growth of fetuses from NK (natural killer
      cells)/MC (mast cells)-deficient mothers that give birth to growth-restricted
      pups and to determine the time point at which IUGR starts. We used high frequency
      ultrasound imaging to follow-up fetal and placenta size and employed Doppler
      measurements to document blood supply to the fetus in females that were deficient
      for NK cells and MCs. In mice lacking NKs and MCs, we observed significantly
      reduced implantation sizes from mid gestation onward, which was further
      associated with smaller placentas. Additionally, NK/MC-deficiency was associated
      with absent and reversed end diastolic flow in umbilical arteries of the fetuses
      and an increased systolic/diastolic ratio as well as an elevated resistance
      index. Together, our results indicate that NKs/MCs promote blood flow, placental
      growth, and subsequent fetal development. The results of this study offer new
      insights as to how fetal growth is affected in vivo in NK/MC-deficient mice,
      whose pups are growth restricted at birth. The use of IUGR models and modern
      technologies enabling the in vivo follow-up of fetal development are important
      tools for understanding mechanisms behind pregnancy complications that in the
      future may lead to the development of effective therapies.

PMID- 29375561
TI  - Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy
      Target across Different Tumor Types.
AB  - Overexpression of the chondroitin sulfate proteoglycan 4 (CSPG4) has been
      associated with the pathology of multiple types of such as melanoma, breast
      cancer, squamous cell carcinoma, mesothelioma, neuroblastoma, adult and pediatric
      sarcomas, and some hematological cancers. CSPG4 has been reported to exhibit a
      role in the growth and survival as well as in the spreading and metastasis of
      tumor cells. CSPG4 is overexpressed in several malignant diseases, while it is
      thought to have restricted and low expression in normal tissues. Thus, CSPG4 has
      become the target of numerous anticancer treatment approaches, including
      monoclonal antibody-based therapies. This study reviews key potential anti-CSPG4
      antibody and immune-based therapies and examines their direct
      antiproliferative/metastatic and immune activating mechanisms of action.

PMID- 29375563
TI  - MicroRNA 27a-3p Regulates Antimicrobial Responses of Murine Macrophages Infected
      by Mycobacterium avium subspecies paratuberculosis by Targeting Interleukin-10
      and TGF-beta-Activated Protein Kinase 1 Binding Protein 2.
AB  - Mycobacterium avium subspecies paratuberculosis (MAP) persistently survive and
      replicate in mononuclear phagocytic cells by adopting various strategies to
      subvert host immune response. Interleukin-10 (IL-10) upregulation via inhibition
      of macrophage bactericidal activity is a critical step for MAP survival and
      pathogenesis within the host cell. Mitogen-activated protein kinase p38 signaling
      cascade plays a crucial role in the elevation of IL-10 and progression of MAP
      pathogenesis. The contribution of microRNAs (miRNAs) and their influence on the
      activation of macrophages during MAP pathogenesis are still unclear. In the
      current study, we found that miRNA-27a-3p (miR-27a) expression is downregulated
      during MAP infection both in vivo and in vitro. Moreover, miR-27a is also
      downregulated in toll-like receptor 2 (TLR2)-stimulated murine macrophages
      (RAW264.7 and bone marrow-derived macrophage). ELISA and real-time qRT-PCR
      results confirm that overexpression of miR-27a inhibited MAP-induced IL-10
      production in macrophages and upregulated pro-inflammatory cytokines, while miR
      27a inhibitor counteracted these effects. Luciferase reporter assay results
      revealed that IL-10 and TGF-beta-activated protein kinase 1 binding protein 2
      (TAB 2) are potential targets of miR-27a. In addition, we demonstrated that miR
      27a negatively regulates TAB 2 expression and diminishes TAB 2-dependent p38/JNK
      phosphorylation, ultimately downregulating IL-10 expression in MAP-infected
      macrophages. Furthermore, overexpression of miR-27a significantly inhibited the
      intracellular survival of MAP in infected macrophages. Our data show that miR-27a
      augments antimicrobial activities of macrophages and inhibits the expression of
      IL-10, demonstrating that miR-27a regulates protective innate immune responses
      during MAP infection and can be exploited as a novel therapeutic target in the
      control of intracellular pathogens, including paratuberculosis.

PMID- 29375565
TI  - Platycodin D Inhibits Inflammatory Response in LPS-Stimulated Primary Rat
      Microglia Cells through Activating LXRalpha-ABCA1 Signaling Pathway.
AB  - Platycodin D (PLD), an effective triterpenesaponin extracted from Platycodon
      grandiflorum, has been known to have anti-inflammatory effect. In the present
      study, we investigate the anti-inflammatory effects of PLD on LPS-induced
      inflammation in primary rat microglia cells. The results showed that PLD
      significantly inhibited LPS-induced ROS, TNF-alpha, IL-6, and IL-1beta production
      in primary rat microglia cells. PLD also inhibited LPS-induced NF-kappaB
      activation. Furthermore, our results showed that PLD prevented LPS-induced TLR4
      translocation into lipid rafts via disrupting the formation of lipid rafts by
      inducing cholesterol efflux. In addition, PLD could activate LXRalpha-ABCA1
      signaling pathway which induces cholesterol efflux from cells. The inhibition of
      inflammatory cytokines by PLD could be reversed by SiRNA of LXRalpha. In
      conclusion, these results indicated that PLD prevented LPS-induced inflammation
      by activating LXRalpha-ABCA1 signaling pathway, which disrupted lipid rafts and
      prevented TLR4 translocation into lipid rafts, thereby inhibiting LPS-induced
      inflammatory response.

PMID- 29375564
TI  - New Insights into the Immunobiology of Mononuclear Phagocytic Cells and Their
      Relevance to the Pathogenesis of Cardiovascular Diseases.
AB  - Macrophages are the primary immune cells that reside within the myocardium,
      suggesting that these mononuclear phagocytes are essential in the orchestration
      of cardiac immunity and homeostasis. Independent of the nature of the injury, the
      heart triggers leukocyte activation and recruitment. However, inflammation is
      harmful to this vital terminally differentiated organ with extremely poor
      regenerative capacity. As such, cardiac tissue has evolved particular strategies
      to increase the stress tolerance and minimize the impact of inflammation. In this
      sense, growing evidences show that mononuclear phagocytic cells are particularly
      dynamic during cardiac inflammation or infection and would actively participate
      in tissue repair and functional recovery. They respond to soluble mediators such
      as metabolites or cytokines, which play central roles in the timing of the
      intrinsic cardiac stress response. During myocardial infarction two distinct
      phases of monocyte influx have been identified. Upon infarction, the heart
      modulates its chemokine expression profile that sequentially and actively
      recruits inflammatory monocytes, first, and healing monocytes, later. In the same
      way, a sudden switch from inflammatory macrophages (with microbicidal effectors)
      toward anti-inflammatory macrophages occurs within the myocardium very shortly
      after infection with Trypanosoma cruzi, the causal agent of Chagas
      cardiomyopathy. While in sterile injury, healing response is necessary to stop
      tissue damage; during an intracellular infection, the anti-inflammatory milieu in
      infected hearts would promote microbial persistence. The balance of mononuclear
      phagocytic cells seems to be also dynamic in atherosclerosis influencing plaque
      initiation and fate. This review summarizes the participation of mononuclear
      phagocyte system in cardiovascular diseases, keeping in mind that the immune
      system evolved to promote the reestablishment of tissue homeostasis following
      infection/injury, and that the effects of different mediators could modulate the
      magnitude and quality of the immune response. The knowledge of the effects
      triggered by diverse mediators would serve to identify new therapeutic targets in
      different cardiovascular pathologies.

PMID- 29375566
TI  - Evidence for B Cell Exhaustion in Chronic Graft-versus-Host Disease.
AB  - Chronic graft-versus-host disease (cGvHD) remains a major complication of
      allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies
      support a role for B cells in the pathogenesis of cGvHD. In this study, we report
      the presence of an expanded population of CD19+CD21- B cells with features of
      exhaustion in the peripheral blood of patients with cGvHD. CD21- B cells were
      significantly increased in patients with active cGvHD compared to patients
      without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%,
      respectively; p < 0.01). Compared with naive (CD27-CD21+) and classical memory
      (CD27+CD21+) B cells, CD19+CD21- B cells in cGvHD were CD10 negative, CD27
      negative and CD20hi, and exhibited features of exhaustion, including increased
      expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and
      altered expression of chemokine and adhesion molecules such as CD11c, CXCR3,
      CCR7, and CD62L. Moreover, CD21- B cells in cGvHD patients were functionally
      exhausted and displayed poor proliferative response and calcium mobilization in
      response to B-cell receptor triggering and CD40 ligation. Finally, the
      frequencies of circulating CD21- B cells correlated with cGvHD severity in
      patients after HSCT. Our study further characterizes B cells in chronic cGVHD and
      supports the use of CD21-CD27-CD10- B cell frequencies as a biomarker of disease
      severity.

PMID- 29375568
TI  - Detection of Pathogen Exposure in African Buffalo Using Non-Specific Markers of
      Inflammation.
AB  - Detecting exposure to new or emerging pathogens is a critical challenge to
      protecting human, domestic animal, and wildlife health. Yet, current techniques
      to detect infections typically target known pathogens of humans or economically
      important animals. In the face of the current surge in infectious disease
      emergence, non-specific disease surveillance tools are urgently needed. Tracking
      common host immune responses indicative of recent infection may have potential as
      a non-specific diagnostic approach for disease surveillance. The challenge to
      immunologists is to identify the most promising markers, which ideally should be
      highly conserved across pathogens and host species, become upregulated rapidly
      and consistently in response to pathogen invasion, and remain elevated beyond
      clearance of infection. This study combined an infection experiment and a
      longitudinal observational study to evaluate the utility of non-specific markers
      of inflammation [NSMI; two acute phase proteins (haptoglobin and serum amyloid
      A), two pro-inflammatory cytokines (IFNgamma and TNF-alpha)] as indicators of
      pathogen exposure in a wild mammalian species, African buffalo (Syncerus caffer).
      Specifically, in the experimental study, we asked (1) How quickly do buffalo
      mount NSMI responses upon challenge with an endemic pathogen, foot-and-mouth
      disease virus; (2) for how long do NSMI remain elevated after viral clearance
      and; (3) how pronounced is the difference between peak NSMI concentration and
      baseline NSMI concentration? In the longitudinal study, we asked (4) Are elevated
      NSMI associated with recent exposure to a suite of bacterial and viral
      respiratory pathogens in a wild population? Among the four NSMI that we tested,
      haptoglobin showed the strongest potential as a surveillance marker in African
      buffalo: concentrations quickly and consistently reached high levels in response
      to experimental infection, remaining elevated for almost a month. Moreover,
      elevated haptoglobin was indicative of recent exposure to two respiratory
      pathogens assessed in the longitudinal study. We hope this work motivates studies
      investigating suites of NSMI as indicators for pathogen exposure in a broader
      range of both pathogen and host species, potentially transforming how we track
      disease burden in natural populations.

PMID- 29375567
TI  - Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency
      Virus-Coinfected Patients.
AB  - Patients with visceral leishmaniasis (VL)-human immunodeficiency virus (HIV)
      coinfection experience increased drug toxicity and treatment failure rates
      compared to VL patients, with more frequent VL relapse and death. In the era of
      VL elimination strategies, HIV coinfection is progressively becoming a key
      challenge, because HIV-coinfected patients respond poorly to conventional VL
      treatment and play an important role in parasite transmission. With limited
      chemotherapeutic options and a paucity of novel anti-parasitic drugs, new
      interventions that target host immunity may offer an effective alternative. In
      this review, we first summarize current views on how VL immunopathology is
      significantly affected by HIV coinfection. We then review current clinical and
      promising preclinical immunomodulatory interventions in the field of VL and
      discuss how these may operate in the context of a concurrent HIV infection.
      Caveats are formulated as these interventions may unpredictably impact the
      delicate balance between boosting of beneficial VL-specific responses and
      deleterious immune activation/hyperinflammation, activation of latent provirus or
      increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a
      target molecule and a more detailed account of the immunological status induced
      by the coinfection as well as surrogate markers of cure and protection are still
      required. We do, however, argue that virologically suppressed VL patients with a
      recovered immune system, in whom effective antiretroviral therapy alone is not
      able to restore protective immunity, can be considered a relevant target group
      for an immunomodulatory intervention. Finally, we provide perspectives on the
      translation of novel theories on synergistic immune cell cross-talk into an
      effective treatment strategy for VL-HIV-coinfected patients.

PMID- 29375569
TI  - The Yin and Yang of Invariant Natural Killer T Cells in Tumor Immunity
      Suppression of Tumor Immunity in the Intestine.
AB  - CD1d-restricted invariant natural killer T (iNKT) cells are known as early
      responding, potent regulatory cells of immune responses. Besides their
      established role in the regulation of inflammation and autoimmune disease,
      numerous studies have shown that iNKT cells have important functions in tumor
      immunosurveillance and control of tumor metastasis. Tumor-infiltrating T helper 1
      (TH1)/cytotoxic T lymphocytes have been associated with a positive prognosis.
      However, inflammation has a dual role in cancer and chronic inflammation is
      believed to be a driving force in many cancers as exemplified in patients with
      inflammatory bowel disease that have an increased risk of colorectal cancer.
      Indeed, NKT cells promote intestinal inflammation in human ulcerative colitis,
      and the associated animal model, indicating that NKT cells may favor tumor
      development in intestinal tissue. In contrast to other cancers, recent data from
      animal models suggest that iNKT cells promote tumor formation in the intestine by
      supporting an immunoregulatory tumor microenvironment and suppressing TH1
      antitumor immunity. Here, we review the role of iNKT cells in suppression of
      tumor immunity in light of iNKT-cell regulation of intestinal inflammation. We
      also discuss suppression of immunity in other situations as well as factors that
      may influence whether iNKT cells have a protective or an immunosuppressive and
      tumor-promoting role in tumor immunity.

PMID- 29375570
TI  - From Human Megakaryocytes to Platelets: Effects of Aspirin on High-Mobility Group
      Box 1/Receptor for Advanced Glycation End Products Axis.
AB  - Platelets (PLTs) are the major source of high-mobility group box 1 (HMGB1), a
      protein that is involved in sterile inflammation of blood vessels and thrombosis.
      Megakaryocytes (MKs) synthesize HMGB1 and transfer both protein and mRNA into
      PLTs and PLT-derived microvesicles (MV). Free HMGB1 found in supernatants of in
      vitro differentiated MKs and in a megakaryoblastic cell line (DAMI cells).
      Aspirin "in vivo" and "in vitro" not only reduces HMGB1 and receptor for advanced
      glycation end products expression on MKs and PLTs but also drives the movement of
      HMGB1 from MKs into PLTs and PLT-derived MV. These findings suggest that
      consumption of low doses of aspirin reduces the risk of atherosclerosis
      complications as well as reducing PLT aggregation by the inhibition of COX-1.

PMID- 29375572
TI  - The Role of Lipid Metabolism in T Lymphocyte Differentiation and Survival.
AB  - The differentiation and effector functions of both the innate and adaptive immune
      system are inextricably linked to cellular metabolism. The features of metabolism
      which affect both arms of the immune system include metabolic substrate
      availability, expression of enzymes, transport proteins, and transcription
      factors which control catabolism of these substrates, and the ability to perform
      anabolic metabolism. The control of lipid metabolism is central to the
      appropriate differentiation and functions of T lymphocytes, and ultimately to the
      maintenance of immune tolerance. This review will focus on the role of fatty acid
      (FA) metabolism in T cell differentiation, effector function, and survival. FAs
      are important sources of cellular energy, stored as triglycerides. They are also
      used as precursors to produce complex lipids such as cholesterol and membrane
      phospholipids. FA residues also become incorporated into hormones and signaling
      moieties. FAs signal via nuclear receptors and their channeling, between storage
      as triacyl glycerides or oxidation as fuel, may play a role in survival or death
      of the cell. In recent years, progress in the field of immunometabolism has
      highlighted diverse roles for FA metabolism in CD4 and CD8 T cell differentiation
      and function. This review will firstly describe the sensing and modulation of the
      environmental FAs and lipid intracellular signaling and will then explore the key
      role of lipid metabolism in regulating the balance between potentially damaging
      pro-inflammatory and anti-inflammatory regulatory responses. Finally the complex
      role of extracellular FAs in determining cell survival will be discussed.

PMID- 29375573
TI  - Unraveling Natural Killer T-Cells Development.
AB  - Natural killer T-cells are a subset of innate-like T-cells with the ability to
      bridge innate and adaptive immunity. There is great interest in harnessing these
      cells to improve tumor therapy; however, greater understanding of invariant NKT
      (iNKT) cell biology is needed. The first step is to learn more about NKT
      development within the thymus. Recent studies suggest lineage separation of
      murine iNKT cells into iNKT1, iNKT2, and iNKT17 cells instead of shared
      developmental stages. This review will focus on these new studies and will
      discuss the evidence for lineage separation in contrast to shared developmental
      stages. The author will also highlight the classifications of murine iNKT cells
      according to identified transcription factors and cytokine production, and will
      discuss transcriptional and posttranscriptional regulations, and the role of
      mammalian target of rapamycin. Finally, the importance of these findings for
      human cancer therapy will be briefly discussed.

PMID- 29375571
TI  - The Troika Host-Pathogen-Extrinsic Factors in Tuberculosis: Modulating
      Inflammation and Clinical Outcomes.
AB  - The already enormous burden caused by tuberculosis (TB) will be further
      aggravated by the association of this disease with modern epidemics, as human
      immunodeficiency virus and diabetes. Furthermore, the increasingly aging
      population and the wider use of suppressive immune therapies hold the potential
      to enhance the incidence of TB. New preventive and therapeutic strategies based
      on recent advances on our understanding of TB are thus needed. In particular,
      understanding the intricate network of events modulating inflammation in TB will
      help to build more effective vaccines and host-directed therapies to stop TB.
      This review integrates the impact of host, pathogen, and extrinsic factors on
      inflammation and the almost scientifically unexplored complexity emerging from
      the interactions between these three factors. We highlight the exciting data
      showing a contribution of this troika for the clinical outcome of TB and the need
      of incorporating it when developing novel strategies to rewire the immune
      response in TB.

PMID- 29375574
TI  - The Role of Skin and Orogenital Microbiota in Protective Immunity and Chronic
      Immune-Mediated Inflammatory Disease.
AB  - The skin and orogenital mucosae, which constitute complex protective barriers
      against infection and injuries, are not only the first to come into contact with
      pathogens but are also colonized by a set of microorganisms that are essential to
      maintain a healthy physiological environment. Using 16S ribosomal RNA metagenomic
      sequencing, scientists recognized that the microorganism colonization has greater
      diversity and variability than previously assumed. These microorganisms, such as
      commensal bacteria, affect the host's immune response against pathogens and
      modulate chronic inflammatory responses. Previously, a single pathogen was
      thought to cause a single disease, but current evidence suggests that dysbiosis
      of the tissue microbiota may underlie the disease status. Dysbiosis results in
      aberrant immune responses at the surface and furthermore, affects the systemic
      immune response. Hence, understanding the initial interaction between the barrier
      surface immune system and local microorganisms is important for understanding the
      overall systemic effects of the immune response. In this review, we describe
      current evidence for the basis of the interactions between pathogens, microbiota,
      and immune cells on surface barriers and offer explanations for how these
      interactions may lead to chronic inflammatory disorders.

PMID- 29375575
TI  - Differences in Expansion Potential of Naive Chimeric Antigen Receptor T Cells
      from Healthy Donors and Untreated Chronic Lymphocytic Leukemia Patients.
AB  - Introduction: Therapy with chimeric antigen receptor T (CART) cells for
      hematological malignancies has shown promising results. Effectiveness of CART
      cells may depend on the ratio of naive (TN) vs. effector (TE) T cells, TN cells
      being responsible for an enduring antitumor activity through maturation.
      Therefore, we investigated factors influencing the TN/TE ratio of CART cells.
      Materials and methods: CART cells were generated upon transduction of peripheral
      blood mononuclear cells with a CD19.CAR-CD28-CD137zeta third generation
      retroviral vector under two different stimulating culture conditions: anti
      CD3/anti-CD28 antibodies adding either interleukin (IL)-7/IL-15 or IL-2. CART
      cells were maintained in culture for 20 days. We evaluated 24 healthy donors
      (HDs) and 11 patients with chronic lymphocytic leukemia (CLL) for the composition
      of cell subsets and produced CART cells. Phenotype and functionality were tested
      using flow cytometry and chromium release assays. Results: IL-7/IL-15
      preferentially induced differentiation into TN, stem cell memory (TSCM: naive
      CD27+ CD95+), CD4+ and CXCR3+ CART cells, while IL-2 increased effector memory
      (TEM), CD56+ and CD4+ T regulatory (TReg) CART cells. The net amplification of
      different CART subpopulations derived from HDs and untreated CLL patients was
      compared. Particularly the expansion of CD4+ CARTN cells differed significantly
      between the two groups. For HDs, this subtype expanded >60-fold, whereas CD4+
      CARTN cells of untreated CLL patients expanded less than 10-fold. Expression of
      exhaustion marker programmed cell death 1 on CARTN cells on day 10 of culture was
      significantly higher in patient samples compared to HD samples. As the percentage
      of malignant B cells was expectedly higher within patient samples, an excessive
      amount of B cells during culture could account for the reduced expansion
      potential of CARTN cells in untreated CLL patients. Final TN/TE ratio stayed <0.3
      despite stimulation condition for patients, whereas this ratio was >2 in samples
      from HDs stimulated with IL-7/IL-15, thus demonstrating efficient CARTN
      expansion. Conclusion: Untreated CLL patients might constitute a challenge for
      long-lasting CART effects in vivo since only a low number of TN among the CART
      product could be generated. Depletion of malignant B cells before starting CART
      production might be considered to increase the TN/TE ratio within the CART
      product.

PMID- 29375576
TI  - M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2
      Monocytes to Osteoclastogenesis.
AB  - Objectives: We investigated the relationships among M1 monocytes, M2 monocytes,
      osteoclast (OC) differentiation ability, and clinical characteristics in patients
      with rheumatoid arthritis (RA). Methods: Peripheral blood mononuclear cells
      (PBMCs) were isolated from RA patients and healthy donors, and we then
      investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated
      cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from
      RA patients and healthy donors to investigate OC differentiation in vitro.
      Results: Forty RA patients and 20 healthy donors were included. Twenty-two
      patients (55%) were anticitrullinated protein antibody (ACPA) positive. The
      median M1/M2 ratio was 0.59 (0.31-1.11, interquartile range). There were no
      significant differences between the RA patients and healthy donors. There was a
      positive correlation between the M1/M2 ratio and the differentiated OC number in
      vitro in RA patients (rho = 0.81, p < 0.001). The ACPA-positive patients had
      significantly higher M1/M2 ratios in vivo (p = 0.028) and significantly greater
      numbers of OCs in vitro (p = 0.005) than the ACPA-negative patients.
      Multivariable regression analysis revealed that the M1/M2 ratio was the sole
      significant contribution factor to in vitro osteoclastogenesis. RA patients with
      M1/M2 ratios >1 (having relatively more M1 monocytes) had higher C-reactive
      protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios
      <=1. M1-dominant monocytes in vitro produced higher concentrations of interleukin
      6 upon stimulation with lipopolysaccharide than M2 monocytes. Conclusion: M1/M2
      monocytes imbalance strongly contributes to osteoclastogenesis of RA patients.
      Our findings cast M1 and M2 monocyte subsets in a new light as a new target of
      treatments for RA to prevent progression of osteoclastic bone destruction.

PMID- 29375578
TI  - An Explorative Biomarker Study for Vaccine Responsiveness after a Primary
      Meningococcal Vaccination in Middle-Aged Adults.
AB  - Introduction: Prevention of infectious diseases in the elderly is essential to
      establish healthy aging. Yet, immunological aging impairs successful vaccination
      of the elderly. Predictive biomarkers for vaccine responsiveness in middle-aged
      adults may help to identify responders and non-responders before reaching old
      age. Therefore, we aimed to determine biomarkers associated with low and high
      responsiveness toward a primary vaccination in middle-aged adults, for which a
      tetravalent meningococcal vaccine was used as a model. Methods: Middle-aged
      adults (50-65 years of age, N = 100), receiving a tetravalent meningococcal
      vaccination, were divided into low and high responders using the functional
      antibody titers at 28 days postvaccination. A total of 48 parameters, including
      absolute numbers of immune cells and serum levels of cytokines and biochemical
      markers, were determined prevaccination in all participants. Heat maps and
      multivariate redundancy analysis (RDA) were used to reveal immune phenotype
      characteristics and associations of the low and high responders. Results: Several
      significant differences in prevaccination immune markers were observed between
      the low and high vaccine responders. Moreover, RDA analysis revealed a
      significant association between the prevaccination immune phenotype and vaccine
      responsiveness. In particular, our analysis pointed at high numbers of CD4 T
      cells, especially naive CD4 and regulatory T subsets, to be associated with low
      vaccine responsiveness. In addition, low responders showed lower prevaccination
      IL-1Ra levels than high responders. Conclusion: This explorative biomarker study
      shows associations between the prevaccination immune phenotype and vaccine
      responsiveness after a primary meningococcal vaccination in middle-aged adults.
      Consequently, these results provide a basis for predictive biomarker discovery
      for vaccine responsiveness that will require validation in larger cohort studies.

PMID- 29375577
TI  - Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or
      Foes?
AB  - The immune system is the most important protective physiological system of the
      organism. It has many connections with other systems and is, in fact, often
      considered as part of the larger neuro-endocrine-immune axis. Most experimental
      data on immune changes with aging show a decline in many immune parameters when
      compared to young healthy subjects. The bulk of these changes is termed
      immunosenescence. Immunosenescence has been considered for some time as
      detrimental because it often leads to subclinical accumulation of pro
      inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm
      aging are suggested to stand at the origin of most of the diseases of the
      elderly, such as infections, cancer, autoimmune disorders, and chronic
      inflammatory diseases. However, an increasing number of immune-gerontologists
      have challenged this negative interpretation of immunosenescence with respect to
      its significance in aging-related alterations of the immune system. If one
      considers these changes from an evolutionary perspective, they can be viewed
      preferably as adaptive or remodeling rather than solely detrimental. Whereas it
      is conceivable that global immune changes may lead to various diseases, it is
      also obvious that these changes may be needed for extended survival/longevity.
      Recent cumulative data suggest that, without the existence of the
      immunosenescence/inflamm-aging duo (representing two sides of the same
      phenomenon), human longevity would be greatly shortened. This review summarizes
      recent data on the dynamic reassessment of immune changes with aging.
      Accordingly, attempts to intervene on the aging immune system by targeting its
      rejuvenation, it may be more suitable to aim to maintain general homeostasis and
      function by appropriately improving immune-inflammatory-functions.

PMID- 29375579
TI  - Hepatitis B Virus Vaccination in HIV-1-Infected Young Adults: A Tool to Reduce
      the Size of HIV-1 Reservoirs?
AB  - During anti-retroviral therapy (ART) HIV-1 persists in cellular reservoirs,
      mostly represented by CD4+ memory T cells. Several approaches are currently being
      undertaken to develop a cure for HIV-1 infection through elimination (or
      reduction) of these reservoirs. Few studies have so far been conducted to assess
      the possibility of reducing the size of HIV-1 reservoirs through vaccination in
      virologically controlled HIV-1-infected children. We recently conducted a
      vaccination study with a combined hepatitis A virus (HAV) and hepatitis B virus
      (HBV) vaccine in 22 HIV-1-infected children. We assessed the size of the virus
      reservoir, measured as total HIV-1 DNA copies in blood cells, pre- and
      postvaccination. In addition, we investigated by immunostaining whether the
      frequencies of CD4+ and CD8+ T cells and parameters of immune activation and
      proliferation on these cells were modulated by vaccination. At 1 month from the
      last vaccination dose, we found that 20 out of 22 children mounted a serological
      response to HBV; a majority of children had antibodies against HAV at baseline.
      The number of HIV-1 DNA copies in blood at 1 month postvaccination was reduced in
      comparison to baseline although this reduction was not statistically significant.
      A significant reduction of HIV-1 DNA copies in blood following vaccination was
      found in 12 children. The frequencies of CD4+ (naive, effector memory) and CD8+
      (central memory) T-cell subpopulations changed following vaccinations and a
      reduction in the activation and proliferation pattern of these cells was also
      noticed. Multivariate linear regression analysis revealed that the frequency of
      CD8+ effector memory T cells prior to vaccination was strongly predictive of the
      reduction of HIV-1 DNA copies in blood following vaccination of the 22 HIV-1
      infected children. The results of this study suggest a beneficial effect of
      vaccination to reduce the size of virus reservoir in HIV-1-infected children
      receiving ART. A reduced frequency of activated CD4+ cells and an increase in
      central memory CD8+ T cells were associated with this finding. Further studies
      should assess whether vaccination is a possible tool to reduce HIV-1 reservoirs.

PMID- 29375580
TI  - Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte
      Colony-Stimulating Factor in Rheumatoid Arthritis Patients.
AB  - Objectives: Granulocyte monocyte colony-stimulating factor (GM-CSF) is currently
      considered a crucial inflammatory mediator and a novel therapeutic target in
      rheumatoid arthritis (RA), despite the fact that its precise cellular sources
      remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes
      from RA patients and its change with antirheumatic therapies. Methods:
      Intracellular GM-CSF expression was assessed by flow cytometry in stimulated
      peripheral B (CD19+) and T (CD3+) cells from RA patients (n = 40), disease (n =
      31 including osteoarthritis n = 15, psoriatic arthritis n = 10, and systemic
      rheumatic diseases n = 6) and healthy (n = 16) controls. The phenotype of GM-CSF+
      B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes
      during methotrexate (MTX, n = 10) or anti-tumor necrosis factor (anti-TNF, n =
      10) therapy. Results: Among untreated RA patients with active disease (Disease
      Activity Score 28-C-reactive protein = 5.6 +/- 0.89) an expanded population of
      peripheral GM-CSF+ B (4.1 +/- 2.2%) and T (3.4 +/- 1.6%) cells was detected
      compared with both disease (1.7 +/- 0.9%, p < 0.0001 and 1.7 +/- 1.3%, p <
      0.0001, respectively) and healthy (0.3 +/- 0.2%, p < 0.0001 and 0.6 +/- 0.6%, p <
      0.0001) controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or
      transitional phenotype (37.12 +/- 18.34% vs. 14.26 +/- 9.46%, p = 0.001 and 30.49
      +/- 15.04% vs. 2.45 +/- 1.84%, p < 0.0001, respectively) and less a memory
      phenotype (21.46 +/- 20.71% vs. 66.99 +/- 16.63%, p < 0.0001) compared to GM-CSF-
      cells. GM-CSF expression in RA patients did not correlate to disease duration,
      activity or serological status. Anti-TNF treatment led to a statistically
      significant decrease in GM-CSF+ B and T cells while MTX had no significant
      effect. Discussion: This is the first study showing an expanded population of GM
      CSF+ B and T lymphocytes in patients with active RA which declined after anti-TNF
      therapy.

PMID- 29375581
TI  - The Interface between Fungal Biofilms and Innate Immunity.
AB  - Fungal biofilms are communities of adherent cells surrounded by an extracellular
      matrix. These biofilms are commonly found during infection caused by a variety of
      fungal pathogens. Clinically, biofilm infections can be extremely difficult to
      eradicate due to their resistance to antifungals and host defenses. Biofilm
      formation can protect fungal pathogens from many aspects of the innate immune
      system, including killing by neutrophils and monocytes. Altered immune
      recognition during this phase of growth is also evident by changes in the
      cytokine profiles of monocytes and macrophages exposed to biofilm. In this
      manuscript, we review the host response to fungal biofilms, focusing on how these
      structures are recognized by the innate immune system. Biofilms formed by
      Candida, Aspergillus, and Cryptococcus have received the most attention and are
      highlighted. We describe common themes involved in the resilience of fungal
      biofilms to host immunity and give examples of biofilm defenses that are pathogen
      specific.

PMID- 29375582
TI  - Impairment of Several Immune Functions and Redox State in Blood Cells of
      Alzheimer's Disease Patients. Relevant Role of Neutrophils in Oxidative Stress.
AB  - Since aging is considered the most risk factor for sporadic Alzheimer's Disease
      (AD), the age-related impairment of the immune system (immunosenescence), based
      on a chronic oxidative-inflammatory stress situation, could play a key role in
      the development and progression of AD. Although AD is accompanied by systemic
      disturbance, reflecting the damage in the brain, the changes in immune response
      and redox-state in different types of blood cells in AD patients have been
      scarcely studied. The aim was to analyze the variations in several immune
      functions and oxidative-inflammatory stress and damage parameters in both
      isolated peripheral neutrophils and mononuclear blood cells, as well as in whole
      blood cells, from patients diagnosed with mild (mAD) and severe AD, and of age
      matched controls (elderly healthy subjects) as well as of adult controls. The
      cognitive decline of all subjects was determined by Mini-Mental State Examination
      (MMSE) test (mAD stage was established at 20 <= MMSE <= 23 score; AD stage at <18
      MMSE; elderly subjects >27 MMSE). The results showed an impairment of the immune
      functions of human peripheral blood neutrophils and mononuclear cells of mAD and
      AD patients in relation to healthy elderly subjects, who showed the typical
      immunosenescence in comparison with the adult individuals. However, several
      alterations were only observed in severe AD patients (lower chemotaxis,
      lipopolysaccharide lymphoproliferation, and interleukin (IL)-10 release; higher
      basal proliferation, tumor necrosis factor (TNF)-alpha release, and IL-10/TNF
      alpha ratio), others only in mAD subjects (higher adherence), meanwhile others
      appeared in both mAD and AD patients (lower phytohemaglutinin lymphoproliferation
      and higher IL-6 release). This impairment of immune functions could be mediated
      by: (1) the higher oxidative stress and damage also observed in blood cells from
      mAD and AD patients and in isolated neutrophils [lower glutathione (GSH) levels,
      high oxidized glutathione (GSSG)/GSH ratio, and GSSG and malondialdehyde
      contents], and (2) the higher release of basal pro-inflammatory cytokines (IL-6
      and TNF-alpha) found in AD patients. Because the immune system parameters studied
      are markers of health and rate of aging, our results supported an accelerated
      immunosenescence in AD patients. We suggest the assessment of oxidative stress
      and function parameters in peripheral blood cells as well as in isolated
      neutrophils and mononuclear cells, respectively, as possible markers of AD
      progression.

PMID- 29375583
TI  - The Expanding Therapeutic Perspective of CCR5 Blockade.
AB  - CCR5 and its interaction with chemokine ligands have been crucial for
      understanding and tackling HIV-1 entry into target cells. However, over time,
      CCR5 has witnessed an impressive transition from being considered rather
      unimportant in physiology and pathology to becoming central in a growing number
      of pathophysiological conditions. It now turns out that the massive efforts
      devoted to combat HIV-1 entry by interfering with CCR5, and the subsequent
      production of chemokine ligand variants, small chemical compounds, and other
      molecular entities and strategies, may set the therapeutic standards for a wealth
      of different pathologies. Expressed on various cell types, CCR5 plays a vital
      role in the inflammatory response by directing cells to sites of inflammation.
      Aside HIV-1, CCR5 has been implicated in other infectious diseases and non
      infectious diseases such as cancer, atherosclerosis, and inflammatory bowel
      disease. Individuals carrying the CCR5Delta32 mutation live a normal life and are
      warranted a natural barrier to HIV-1 infection. Therefore, CCR5 antagonism and
      gene-edited knockout of the receptor gained growing interest for the therapeutic
      role that CCR5 blockade may play in the attenuation of the severity or
      progression of numerous diseases.

PMID- 29375584
TI  - A Novel Vaccine Delivery Model of the Apicomplexan Eimeria tenella Expressing
      Eimeria maxima Antigen Protects Chickens against Infection of the Two Parasites.
AB  - Vaccine delivery is critical in antigen discovery and vaccine efficacy and
      safety. The diversity of infectious diseases in humans and livestock has required
      the development of varied delivery vehicles to target different pathogens. In
      livestock animals, previous strategies for the development of coccidiosis
      vaccines have encountered several hurdles, limiting the development of multiple
      species vaccine formulations. Here, we describe a novel vaccine delivery system
      using transgenic Eimeria tenella expressing immunodominant antigens of Eimeria
      maxima. In this delivery system, the immune mapped protein 1 of E. maxima
      (EmIMP1) was delivered by the closely related species of E. tenella to the host
      immune system during the whole endogenous life cycle. The overexpression of the
      exogenous antigen did not interfere with the reproduction and immunogenicity of
      transgenic Eimeria. After immunization with the transgenic parasite, we detected
      EmIMP1's and E. maxima oocyst antigens' specific humoral and cellular immune
      responses. In particular, we observed partial protection of chickens immunized
      with transgenic E. tenella against subsequent E. maxima infections. Our results
      demonstrate that the transgenic Eimeria parasite is an ideal coccidia antigen
      delivery vehicle and represents a new type of coccidiosis vaccines. In addition,
      this model could potentially be used in the development of malaria live
      sporozoite vaccines, in which antigens from different strains can be expressed in
      the vaccine strain.

PMID- 29375585
TI  - Streptococcus pneumoniae Attenuated Strain SPY1 with an Artificial Mineral Shell
      Induces Humoral and Th17 Cellular Immunity and Protects Mice against Pneumococcal
      Infection.
AB  - Streptococcus pneumoniae is a major pathogen leading to substantial morbidity and
      mortality in children under 5 years of age. Vaccination is an effective strategy
      to prevent S. pneumoniae infection. SPY1 is a pneumococcal vaccine candidate
      strain obtained in our previous study. To improve its stability and
      immunogencity, in this study, we constructed the SPY1DeltalytA strain that lacks
      autolysin activity and was coated with an artificial exterior surface calcium
      phosphate shell by in situ mineralization. The resulting strain SPY1DeltalytACaPi
      displayed enhanced thermal stability enabling storage at 37 degrees C for 1 week.
      Furthermore, mucosal and subcutaneous immunization with the SPY1DeltalytACaPi
      strain induced better protective effects than SPY1DeltalytA in anti-colonization
      after challenging with 19F and anti-invasion by D39 in mice. Subcutaneous
      immunization with SPY1DeltalytACaPi elicited higher IgG level while mucosal
      immunization primarily elicited an immune response which is supposed to be
      related to Th17 cells. Taken together, the mineralized strain may be a promising
      candidate for an attenuated S. pneumoniae vaccine.

PMID- 29375586
TI  - Host-Derived Leukotriene B4 Is Critical for Resistance against Invasive Pulmonary
      Aspergillosis.
AB  - Aspergillus fumigatus is a mold that causes severe pulmonary infections. Our
      knowledge of how immune competent hosts maintain control of fungal infections
      while constantly being exposed to fungi is rapidly emerging. It is known that
      timely neutrophil recruitment to and activation in the lungs is critical to the
      host defense against development of invasive pulmonary aspergillosis, but the
      inflammatory sequelae necessary remains to be fully defined. Here, we show that 5
      Lipoxygenase (5-LO) and Leukotriene B4 (LTB4) are critical for leukocyte
      recruitment and resistance to pulmonary A. fumigatus challenge in a fungal-strain
      dependent manner. 5-LO activity was needed in radiosensitive cells for an optimal
      anti-fungal response and in vivo LTB4 production was at least partially dependent
      on myeloid-derived hypoxia inducible factor-1alpha. Overall, this study reveals a
      role for host-derived leukotriene synthesis in innate immunity to A. fumigatus.

PMID- 29375587
TI  - Drought Sensitivity of the Carbon Isotope Composition of Leaf Dark-Respired CO2
      in C3 (Leymus chinensis) and C4 (Chloris virgata and Hemarthria altissima)
      Grasses in Northeast China.
AB  - Whether photosynthetic pathway differences exist in the amplitude of nighttime
      variations in the carbon isotope composition of leaf dark-respired CO2
      (delta13Cl) and respiratory apparent isotope fractionation relative to biomass
      (DeltaR,biomass) in response to drought stress is unclear. These differences, if
      present, would be important for the partitioning of C3-C4 mixed ecosystem C
      fluxes. We measured delta13Cl, the delta13C of biomass and of potential
      respiratory substrates and leaf gas exchange in one C3 (Leymus chinensis) and two
      C4 (Chloris virgata and Hemarthria altissima) grasses during a manipulated
      drought period. For all studied grasses, delta13Cl decreased from 21:00 to 03:00
      h. The magnitude of the nighttime shift in delta13Cl decreased with increasing
      drought stress. The delta13Cl values were correlated with the delta13C of
      respiratory substrates, whereas the magnitude of the nighttime shift in delta13Cl
      strongly depended on the daytime carbon assimilation rate and the range of
      nighttime variations in the respiratory substrate content. The DeltaR,biomass in
      the C3 and C4 grasses varied in opposite directions with the intensification of
      the drought stress. The contribution of C4 plant-associated carbon flux is likely
      to be overestimated if carbon isotope signatures are used for the partitioning of
      ecosystem carbon exchange and the delta13C of biomass is used as a substitute for
      leaf dark-respired CO2. The detected drought sensitivities in delta13Cl and
      differences in respiratory apparent isotope fractionation between C3 and C4
      grasses have marked implications for isotope partitioning studies at the
      ecosystem level.

PMID- 29375589
TI  - Bryophytes and Organic layers Control Uptake of Airborne Nitrogen in Low-N
      Environments.
AB  - The effects of atmospheric nitrogen (N) deposition on ecosystem functioning
      largely depend on the retention of N in different ecosystem compartments, but
      accumulation and partitioning processes have rarely been quantified in long-term
      field experiments. In the present study we analysed for the first time decadal
      scale flows and allocation patterns of N in a heathland ecosystem that has been
      subject to airborne N inputs over decades. Using a long-term 15N tracer
      experiment, we quantified N retention and flows to and between ecosystem
      compartments (above-ground/below-ground vascular biomass, moss layer, soil
      horizons, leachate). After 9 years, about 60% of the added 15N-tracer remained in
      the N cycle of the ecosystem. The moss layer proved to be a crucial link between
      incoming N and its allocation to different ecosystem compartments (in terms of a
      short-term capture, but long-term release function). However, about 50% of the
      15N captured and released by the moss layer was not compensated for by a
      corresponding increase in recovery rates in any other compartment, probably due
      to denitrification losses from the moss layer in the case of water saturation
      after rain events. The O-horizon proved to be the most important long-term sink
      for added 15N, as reflected by an increase in recovery rates from 18 to 40%
      within 8 years. Less than 2.1% of 15N were recovered in the podzol-B-horizon,
      suggesting that only negligible amounts of N were withdrawn from the N cycle of
      the ecosystem. Moreover, 15N recovery was low in the dwarf shrub above-ground
      biomass (<3.9% after 9 years) and in the leachate (about 0.03% within 1 year),
      indicating still conservative N cycles of the ecosystem, even after decades of N
      inputs beyond critical load thresholds. The continuous accumulation of reactive
      forms of airborne N suggests that critical load-estimates need to account for
      cumulative effects of N additions into ecosystems.

PMID- 29375588
TI  - Advanced DNA-Based Point-of-Care Diagnostic Methods for Plant Diseases Detection.
AB  - Diagnostic technologies for the detection of plant pathogens with point-of-care
      capability and high multiplexing ability are an essential tool in the fight to
      reduce the large agricultural production losses caused by plant diseases. The
      main desirable characteristics for such diagnostic assays are high specificity,
      sensitivity, reproducibility, quickness, cost efficiency and high-throughput
      multiplex detection capability. This article describes and discusses various DNA
      based point-of care diagnostic methods for applications in plant disease
      detection. Polymerase chain reaction (PCR) is the most common DNA amplification
      technology used for detecting various plant and animal pathogens. However,
      subsequent to PCR based assays, several types of nucleic acid amplification
      technologies have been developed to achieve higher sensitivity, rapid detection
      as well as suitable for field applications such as loop-mediated isothermal
      amplification, helicase-dependent amplification, rolling circle amplification,
      recombinase polymerase amplification, and molecular inversion probe. The
      principle behind these technologies has been thoroughly discussed in several
      review papers; herein we emphasize the application of these technologies to
      detect plant pathogens by outlining the advantages and disadvantages of each
      technology in detail.

PMID- 29375590
TI  - Characterization of Linkage Disequilibrium and Population Structure in a Mungbean
      Diversity Panel.
AB  - Mungbean [Vigna radiata (L.) R. Wilczek var. radiata] is an important grain
      legume globally, providing a high-quality plant protein source largely produced
      and consumed in South and East Asia. This study aimed to characterize a mungbean
      diversity panel consisting of 466 cultivated accessions and demonstrate its
      utility by conducting a pilot genome-wide association study of seed coat color.
      In addition 16 wild accessions were genotyped for comparison and in total over
      22,000 polymorphic genome-wide SNPs were identified and used to analyze the
      genetic diversity, population structure, linkage disequilibrium (LD) of mungbean.
      Polymorphism was lower in the cultivated accessions in comparison to the wild
      accessions, with average polymorphism information content values 0.174, versus
      0.305 in wild mungbean. LD decayed in ~100 kb in cultivated lines, a distance
      higher than the linkage decay of ~60 kb estimated in wild mungbean. Four distinct
      subgroups were identified within the cultivated lines, which broadly corresponded
      to geographic origin and seed characteristics. In a pilot genome-wide association
      mapping study of seed coat color, five genomic regions associated were
      identified, two of which were close to seed coat color genes in other species.
      This mungbean diversity panel constitutes a valuable resource for genetic
      dissection of important agronomical traits to accelerate mungbean breeding.

PMID- 29375592
TI  - Novel Insights into the Influence of Seed Sarcotesta Photosynthesis on
      Accumulation of Seed Dry Matter and Oil Content in Torreya grandis cv.
      "Merrillii".
AB  - Seed oil content is an important trait of nut seeds, and it is affected by the
      import of carbon from photosynthetic sources. Although green leaves are the main
      photosynthetic organs, seed sarcotesta photosynthesis also supplies assimilates
      to seed development. Understanding the relationship between seed photosynthesis
      and seed development has theoretical and practical significance in the
      cultivation of Torreya grandis cv. "Merrillii." To assess the role of seed
      sarcotesta photosynthesis on the seed development, anatomical and physiological
      traits of sarcotesta were measured during two growing seasons in the field.
      Compared with the attached current-year leaves, the sarcotesta had higher gross
      photosynthetic rate at the first stage of seed development. At the late second
      stage of seed development, sarcotesta showed down-regulation of PSII activity, as
      indicated by significant decrease in the following chlorophyll fluorescence
      parameters: the maximum PSII efficiency (Fv/Fm ), the PSII quantum yield (Phi
      PSII ), and the photosynthetic quenching coefficient (qP). The ribulose 1, 5
      bisphosphate carboxylase (Rubisco) activity, the total chlorophyll content
      (Chl(a+b)) and nitrogen content in the sarcotesta were also significantly
      decreased during that period. Treatment with DCMU [3-(3,4-dichlorophenyl)-1,1
      dimethylurea] preventing seed photosynthesis decreased the seed dry weight and
      the oil content by 25.4 and 25.5%, respectively. We conclude that seed
      photosynthesis plays an important role in the dry matter accumulation at the
      first growth stage. Our results also suggest that down-regulation of seed
      photosynthesis is a plant response to re-balance the source-sink ratio at the
      second growth stage. These results suggest that seed photosynthesis is important
      for biomass accumulation and oil synthesis of the Torreya seeds. The results will
      facilitate achieving higher yields and oil contents in nut trees by selection for
      higher seed photosynthesis cultivars.

PMID- 29375593
TI  - Editorial: Plant Phenotyping and Phenomics for Plant Breeding.

PMID- 29375591
TI  - The Integration of Electrical Signals Originating in the Root of Vascular Plants.
AB  - Plants have developed different signaling systems allowing for the integration of
      environmental cues to coordinate molecular processes associated to both early
      development and the physiology of the adult plant. Research on systemic signaling
      in plants has traditionally focused on the role of phytohormones as long-distance
      signaling molecules, and more recently the importance of peptides and miRNAs in
      building up this communication process has also been described. However, it is
      well-known that plants have the ability to generate different types of long-range
      electrical signals in response to different stimuli such as light, temperature
      variations, wounding, salt stress, or gravitropic stimulation. Presently, it is
      unclear whether short or long-distance electrical communication in plants is
      linked to nutrient uptake. This review deals with aspects of sensory input in
      plant roots and the propagation of discrete signals to the plant body. We discuss
      the physiological role of electrical signaling in nutrient uptake and how
      nutrient variations may become an electrical signal propagating along the plant.

PMID- 29375594
TI  - Improving Crop Yield and Nutrient Use Efficiency via Biofertilization-A Global
      Meta-analysis.
AB  - The application of microbial inoculants (biofertilizers) is a promising
      technology for future sustainable farming systems in view of rapidly decreasing
      phosphorus stocks and the need to more efficiently use available nitrogen (N).
      Various microbial taxa are currently used as biofertilizers, based on their
      capacity to access nutrients from fertilizers and soil stocks, to fix atmospheric
      nitrogen, to improve water uptake or to act as biocontrol agents. Despite the
      existence of a considerable knowledge on effects of specific taxa of
      biofertilizers, a comprehensive quantitative assessment of the performance of
      biofertilizers with different traits such as phosphorus solubilization and N
      fixation applied to various crops at a global scale is missing. We conducted a
      meta-analysis to quantify benefits of biofertilizers in terms of yield increase,
      nitrogen and phosphorus use efficiency, based on 171 peer reviewed publications
      that met eligibility criteria. Major findings are: (i) the superiority of
      biofertilizer performance in dry climates over other climatic regions (yield
      response: dry climate +20.0 +/- 1.7%, tropical climate +14.9 +/- 1.2%, oceanic
      climate +10.0 +/- 3.7%, continental climate +8.5 +/- 2.4%); (ii) meta-regression
      analyses revealed that yield response due to biofertilizer application was
      generally small at low soil P levels; efficacy increased along higher soil P
      levels in the order arbuscular mycorrhizal fungi (AMF), P solubilizers, and N
      fixers; (iii) meta-regressions showed that the success of inoculation with AMF
      was greater at low organic matter content and at neutral pH. Our comprehensive
      analysis provides a basis and guidance for proper choice and application of
      biofertilizers.

PMID- 29375595
TI  - No Time to Waste: Transcriptome Study Reveals that Drought Tolerance in Barley
      May Be Attributed to Stressed-Like Expression Patterns that Exist before the
      Occurrence of Stress.
AB  - Plant survival in adverse environmental conditions requires a substantial change
      in the metabolism, which is reflected by the extensive transcriptome rebuilding
      upon the occurrence of the stress. Therefore, transcriptomic studies offer an
      insight into the mechanisms of plant stress responses. Here, we present the
      results of global gene expression profiling of roots and leaves of two barley
      genotypes with contrasting ability to cope with drought stress. Our analysis
      suggests that drought tolerance results from a certain level of transcription of
      stress-influenced genes that is present even before the onset of drought. Genes
      that predispose the plant to better drought survival play a role in the
      regulatory network of gene expression, including several transcription factors,
      translation regulators and structural components of ribosomes. An important group
      of genes is involved in signaling mechanisms, with significant contribution of
      hormone signaling pathways and an interplay between ABA, auxin, ethylene and
      brassinosteroid homeostasis. Signal transduction in a drought tolerant genotype
      may be more efficient through the expression of genes required for environmental
      sensing that are active already during normal water availability and are related
      to actin filaments and LIM domain proteins, which may function as osmotic
      biosensors. Better survival of drought may also be attributed to more effective
      processes of energy generation and more efficient chloroplasts biogenesis.
      Interestingly, our data suggest that several genes involved in a photosynthesis
      process are required for the establishment of effective drought response not only
      in leaves, but also in roots of barley. Thus, we propose a hypothesis that root
      plastids may turn into the anti-oxidative centers protecting root macromolecules
      from oxidative damage during drought stress. Specific genes and their potential
      role in building up a drought-tolerant barley phenotype is extensively discussed
      with special emphasis on processes that take place in barley roots. When
      possible, the interconnections between particular factors are emphasized to draw
      a broader picture of the molecular mechanisms of drought tolerance in barley.

PMID- 29375596
TI  - Nictaba Homologs from Arabidopsis thaliana Are Involved in Plant Stress
      Responses.
AB  - Plants are constantly exposed to a wide range of environmental stresses, but
      evolved complicated adaptive and defense mechanisms which allow them to survive
      in unfavorable conditions. These mechanisms protect and defend plants by using
      different immune receptors located either at the cell surface or in the
      cytoplasmic compartment. Lectins or carbohydrate-binding proteins are widespread
      in the plant kingdom and constitute an important part of these immune receptors.
      In the past years, lectin research has focused on the stress-inducible lectins.
      The Nicotiana tabacum agglutinin, abbreviated as Nictaba, served as a model for
      one family of stress-related lectins. Here we focus on three non-chimeric Nictaba
      homologs from Arabidopsis thaliana, referred to as AN3, AN4, and AN5. Confocal
      microscopy of ArathNictaba enhanced green fluorescent protein (EGFP) fusion
      constructs transiently expressed in N. benthamiana or stably expressed in A.
      thaliana yielded fluorescence for AN4 and AN5 in the nucleus and the cytoplasm of
      the plant cell, while fluorescence for AN3 was only detected in the cytoplasm. RT
      qPCR analysis revealed low expression for all three ArathNictabas in different
      tissues throughout plant development. Stress application altered the expression
      levels, but all three ArathNictabas showed a different expression pattern.
      Pseudomonas syringae infection experiments with AN4 and AN5 overexpression lines
      demonstrated a significantly higher tolerance of several transgenic lines to P.
      syringae compared to wild type plants. Finally, AN4 was shown to interact with
      two enzymes involved in plant defense, namely TGG1 and BGLU23. Taken together,
      our data suggest that the ArathNictabas represent stress-regulated proteins with
      a possible role in plant stress responses. On the long term this research can
      contribute to the development of more stress-resistant plants.

PMID- 29375597
TI  - Cadmium Stress Leads to Rapid Increase in RNA Oxidative Modifications in Soybean
      Seedlings.
AB  - Increase in the level of reactive oxygen species (ROS) is a common response to
      stress factors, including exposure to metals. ROS over-production is associated
      with oxidation of lipids, proteins, and nucleic acids. It is suggested that the
      products of oxidation are not solely the markers of oxidative stress but also
      signaling elements. For instance, it has been shown in animal models that mRNA
      oxidation is a selective process engaged in post-transcriptional regulation of
      genes expression and that it is associated with the development of symptoms of
      several neurodegenerative disorders. In the present study, we examined the impact
      of short-term cadmium (Cd) stress on the level of two RNA oxidation markers: 8
      hydroxyguanosine (8-OHG) and apurinic/apyrimidinic sites (AP-sites, abasic
      sites). In the case of 8-OHG, a significant increase was observed after 3 h of
      exposure to moderate Cd concentration (10 mg/l). In turn, high level of AP-sites,
      accompanied by strong ROS accumulation and lipid peroxidation, was noted only
      after 24 h of treatment with higher Cd concentration (25 mg/l). This is the first
      report showing induction of RNA oxidations in plants response to stress factors.
      The possible signaling and gene regulatory role of oxidatively modified
      transcripts is discussed.

PMID- 29375598
TI  - OsWRKY67 Plays a Positive Role in Basal and XA21-Mediated Resistance in Rice.
AB  - WRKY proteins play important roles in transcriptional reprogramming in plants in
      response to various stresses including pathogen attack. In this study, we
      functionally characterized a rice WRKY gene, OsWRKY67, whose expression is
      upregulated against pathogen challenges. Activation of OsWRKY67 by T-DNA tagging
      significantly improved the resistance against two rice pathogens, Magnaporthe
      oryzae and Xanthomonas oryzae pv. oryzae (Xoo). Reactive oxygen species (ROS)
      rapidly accumulated in OsWRKY67 activation mutant lines in response to elicitor
      treatment, compared with the controls. Overexpression of OsWRKY67 in rice
      confirmed enhanced disease resistance, but led to a restriction of plant growth
      in transgenic lines with high levels of OsWRKY67 protein. OsWRKY67 RNAi lines
      significantly reduced resistance to M. oryzae and Xoo isolates tested, and
      abolished XA21-mediated resistance, implying the possibility of broad-spectrum
      resistance from OsWRKY67. Transcriptional activity and subcellular localization
      assays indicated that OsWRKY67 is present in the nucleus where it functions as a
      transcriptional activator. Quantitative PCR revealed that the pathogenesis
      related genes, PR1a, PR1b, PR4, PR10a, and PR10b, are upregulated in OsWRKY67
      overexpression lines. Therefore, these results suggest that OsWRKY67 positively
      regulates basal and XA21-mediated resistance, and is a promising candidate for
      genetic improvement of disease resistance in rice.

PMID- 29375599
TI  - Genetic Transformation System for Woody Plant Tripterygium wilfordii and Its
      Application to Product Natural Celastrol.
AB  - Tripterygium wilfordii is a perennial woody liana medicinal plant with several
      crucial biological activities. Although studies on tissue culture have previously
      been conducted, research on genetic transformation is much more challenging and
      therefore results in slower progress. In the present study, a highly efficient
      transformation system involving the particle bombardment of T. wilfordii with the
      reporter egfp gene using the PDS-1000/He system was established. A total of seven
      parameters affecting the genetic transformation were investigated using an L18 (6
      * 36)-type orthogonal array. The result indicated that DNA delivery conditions of
      3-cm target distance, 1100 psi helium pressure, 28 mmHg chamber vacuum pressure,
      three times number of bombardment, CaCl2 as precipitation agent, 2 MUg plasmid
      DNA concentration and 48 h post-bombardment incubation time were optimal for T.
      wilfordii cell suspensions transformation. The average transformation efficiency
      was 19.17%. Based on this transformation system, the overexpression of two T.
      wilfordii farnesyl pyrophosphate synthase genes (TwFPSs) was performed in cell
      suspensions. Integration of the TwFPSs in the genome was verified by PCR analysis
      and also by Southern blotting using hygromycin gene as a probe. Real-time
      quantitative PCR analysis showed that the expression of TwFPS1&2 was highly up
      regulated in transgenic cell suspensions compared with control cells. The
      detection of metabolites showed that TwFPS1&2 could highly increase the celastrol
      content (973.60 MUg/g) in transgenic cells. These results indicated that this
      transformation system is an effective protocol for characterizing the function of
      genes in the terpenoid biosynthetic pathway.

PMID- 29375600
TI  - Drought Stress and Root-Associated Bacterial Communities.
AB  - Root-associated bacterial communities play a vital role in maintaining health of
      the plant host. These communities exist in complex relationships, where
      composition and abundance of community members is dependent on a number of
      factors such as local soil chemistry, plant genotype and phenotype, and
      perturbations in the surrounding abiotic environment. One common perturbation,
      drought, has been shown to have drastic effects on bacterial communities, yet
      little is understood about the underlying causes behind observed shifts in
      microbial abundance. As drought may affect root bacterial communities both
      directly by modulating moisture availability, as well as indirectly by altering
      soil chemistry and plant phenotypes, we provide a synthesis of observed trends in
      recent studies and discuss possible directions for future research that we hope
      will provide for more knowledgeable predictions about community responses to
      future drought events.

PMID- 29375601
TI  - Arabidopsis G-Protein beta Subunit AGB1 Interacts with BES1 to Regulate
      Brassinosteroid Signaling and Cell Elongation.
AB  - In Arabidopsis, brassinosteroids (BR) are major growth-promoting hormones, which
      integrate with the heterotrimeric guanine nucleotide-binding protein (G-protein)
      signals and cooperatively modulate cell division and elongation. However, the
      mechanisms of interaction between BR and G-protein are not well understood. Here,
      we show that the G-protein beta subunit AGB1 directly interacts with the BR
      transcription factor BES1 in vitro and in vivo. An AGB1-null mutant, agb1-2,
      displays BR hyposensitivity and brassinazole (BRZ, BR biosynthesis inhibitor)
      hypersensitivity, which suggests that AGB1 positively mediates the BR signaling
      pathway. Moreover, we demonstrate that AGB1 synergistically regulates expression
      of BES1 target genes, including the BR biosynthesis genes CPD and DWF4 and the
      SAUR family genes required for promoting cell elongation. Further, Western blot
      analysis of BES1 phosphorylation states indicates that the interaction between
      AGB1 and BES1 alters the phosphorylation status of BES1 and increases the ratio
      of dephosphorylated to phosphorylated BES1, which leads to accumulation of
      dephosphorylated BES1 in the nucleus. Finally, AGB1 promotes BES1 binding to BR
      target genes and stimulates the transcriptional activity of BES1. Taken together,
      our results demonstrate that AGB1 positively regulates cell elongation by
      affecting the phosphorylation status and transcriptional activity of BES1.

PMID- 29375603
TI  - Ca Distribution Pattern in Litchi Fruit and Pedicel and Impact of Ca Channel
      Inhibitor, La3.
AB  - Calcium (Ca) deficiency in fruit causes various physiological disorders leading
      to quality loss. However, disorders related to Ca deficiency are not simply
      caused by a shortage of calcium supply. Ca distribution is also an important
      relation. This study examined Ca distribution pattern in fruit and pedicel in
      litchi (Litchi chinensis Sonn.) and the influence of Ca channel inhibitor La3+ on
      fruit Ca uptake and distribution. In situ distribution of Ca in the phloem and
      xylem tissues of the pedicel was visualized by Ca mapping with X-ray
      microanalyzer. Ca2+ analogy Sr2+ was used to trace Ca2+ transport pathway to
      fruit as well as distribution pattern. The results showed Ca was more distributed
      in the pericarp, especially the distal part. Ca level in the bark/phloem was
      always significantly higher than in the xylem and increased with stem age,
      suggesting constant influx of Ca into the phloem from the xylem. La3+ increased
      the ratio of Ca in the xylem to that in the bark in the pedicel and significantly
      reduced Ca accumulation by 55.6% in fruit, suggesting influx of Ca into the
      symplast was involved in fruit Ca uptake. Sr2+ introduced from fruit stalk was
      found to be transported to fruit through the phloem as Sr was largely distributed
      in the phloem, and fruit stalk girdling significantly reduced Sr accumulation in
      the pericarp. Ca mapping across the pedicel revealed Ca-rich sites in the
      parenchyma cells in the phloem and along the cambium, where abundant Ca oxalate
      crystals were found. The results suggested extensive influx of Ca from
      xylem/apoplast pathway into the phloem/symplast pathway in the pedicel, which
      enables phloem/symplast pathway to contribute a considerable part to Ca uptake in
      litchi fruit.

PMID- 29375602
TI  - Genetic Architecture of Capitate Glandular Trichome Density in Florets of
      Domesticated Sunflower (Helianthus annuus L.).
AB  - Capitate glandular trichomes (CGT), one type of glandular trichomes, are most
      common in Asteraceae species. CGT can produce various secondary metabolites such
      as sesquiterpene lactones (STLs) and provide durable resistance to insect pests.
      In sunflower, CGT-based host resistance is effective to combat the specialist
      pest, sunflower moth. However, the genetic basis of CGT density is not well
      understood in sunflower. In this study, we identified two major QTL controlling
      CGT density in sunflower florets by using a F4 mapping population derived from
      the cross HA 300 * RHA 464 with a genetic linkage map constructed from genotyping
      by-sequencing data and composed of 2121 SNP markers. One major QTL is located on
      chromosome 5, which explained 11.61% of the observed phenotypic variation, and
      the second QTL is located on chromosome 6, which explained 14.06% of the observed
      phenotypic variation. The QTL effects and the association between CGT density and
      QTL support interval were confirmed in a validation population which included 39
      sunflower inbred lines with diverse genetic backgrounds. We also identified two
      strong candidate genes in the QTL support intervals, and the functions of their
      orthologs in other plant species suggested their potential roles in regulating
      capitate glandular trichome density in sunflower. Our results provide valuable
      information to sunflower breeding community for developing host resistance to
      sunflower insect pests.

PMID- 29375604
TI  - UDP-Glucose: A Potential Signaling Molecule in Plants?
AB  - This perspective paper focuses on the most recent results suggesting a potential
      role for UDP-Glucose as a signaling molecule in plants. In animals, UDP-Glucose
      is well-established as an extracellular signaling molecule that is sensed by G
      protein coupled receptors, activating several downstream defense mechanisms.
      Recent studies have shown that abnormal growth occurred in both vegetative and
      reproductive tissue of plants with reduced UDP-Glucose levels, and this could be
      rescued by exogenous UDP-Glucose. In plants with increased biomass accumulation,
      the genes involved in UDP-Glucose production were up-regulated. However,
      excessive endogenous accumulation of UDP-Glucose induced programmed cell death
      (PCD), and this could also be obtained by exogenous UDP-Glucose application.
      Plants with decreased UDP-glucose were insensitive to pathogen induced PCD. We
      speculate that UDP-Glucose acts as an extracellular signaling molecule in plants,
      and that it may be perceived as a damage-associated molecular pattern.

PMID- 29375605
TI  - Overlapping Residual Herbicides for Control of Photosystem (PS) II- and 4
      Hydroxyphenylpyruvate Dioxygenase (HPPD)-Inhibitor-Resistant Palmer amaranth
      (Amaranthus palmeri S. Watson) in Glyphosate-Resistant Maize.
AB  - A Palmer amaranth (Amaranthus palmeri S. Watson) biotype has evolved resistance
      to photosystem (PS) II- (atrazine) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)
      inhibiting herbicides (mesotrione, tembotrione, and topramezone) in maize seed
      production field in Nebraska, USA. The objectives of this study were to determine
      the effect of soil residual pre-emergence (PRE) herbicides followed by (fb) tank
      mixture of residual and foliar active post-emergence (POST) herbicides on PS-II-
      and HPPD-inhibitor-resistant Palmer amaranth control, maize yield, and net
      economic returns. Field experiments were conducted in a grower's field infested
      with PS II- and HPPD-inhibitor-resistant Palmer amaranth near Shickley in
      Fillmore County, Nebraska, USA in 2015 and 2016. The contrast analysis suggested
      that saflufenacil plus dimethenamid-P or pyroxasulfone plus saflufenacil applied
      PRE provided 80-82% Palmer amaranth control compared to 65 and 39% control with
      saflufenacil and pyroxasulfone applied alone at 3 weeks after PRE (WAPRE),
      respectively. Among the PRE fb POST herbicide programs, 95-98% Palmer amaranth
      control was achieved with pyroxasulfone plus safluefenacil, or saflufenacil plus
      dimethenamid-P applied PRE, fb glyphosate plus topramezone plus dimethenamid-P
      plus atrazine, glyphosate plus diflufenzopyr plus dicamba plus pyroxasulfone,
      glyphosate plus diflufenzopyr plus pendimethalin, or glyphosate plus
      diflufenzopyr plus dicamba plus atrazine applied POST at 3 weeks after POST
      (WAPOST) through maize harvest. Based on contrast analysis, PRE fb POST programs
      provided 77-83% Palmer amaranth control at 3 WAPOST through maize harvest
      compared to 12-15% control with PRE-only and 66-84% control with POST-only
      programs. Similarly, PRE fb POST programs provided 99% biomass reduction at 6
      WAPOST compared to PRE-only (28%) and POST-only (87%) programs. PRE fb POST
      programs provided higher maize yield (13,617 kg ha-1) and net return (US $1,724
      ha-1) compared to the PRE-only (2,656 kg ha-1; US $285 ha-1) and POST-only
      (11,429 kg ha-1; US $1,539 ha-1) programs. The results indicated that effective
      control of multiple herbicide-resistant Palmer amaranth can be achieved with PRE
      fb POST programs that include herbicides with overlapping residual activity to
      maintain season-long control.

PMID- 29375607
TI  - Non-targeted Colonization by the Endomycorrhizal Fungus, Serendipita vermifera,
      in Three Weeds Typically Co-occurring with Switchgrass.
AB  - Serendipita vermifera (=Sebacina vermifera; isolate MAFF305830) is a mycorrhizal
      fungus originally isolated from the roots of an Australian orchid that we have
      previously shown to be beneficial in enhancing biomass yield and drought
      tolerance in switchgrass, an important bioenergy crop for cellulosic ethanol
      production in the United States. However, almost nothing is known about how this
      root-associated fungus proliferates and grows through the soil matrix. Such
      information is critical to evaluate the possibility of non-target effects, such
      as unintended spread to weedy plants growing near a colonized switchgrass plant
      in a field environment. A microcosm experiment was conducted to study movement of
      vegetative mycelia of S. vermifera between intentionally inoculated switchgrass
      (Panicum virgatum L.) and nearby weeds. We constructed size-exclusion microcosms
      to test three different common weeds, large crabgrass (Digitaria sanguinalis L.),
      Texas panicum (Panicum texanum L.), and Broadleaf signalgrass (Brachiaria
      platyphylla L.), all species that typically co-occur in Southern Oklahoma and
      potentially compete with switchgrass. We report that such colonization of non
      target plants by S. vermifera can indeed occur, seemingly via co-mingled root
      systems. As a consequence of colonization, significant enhancement of growth was
      noted in signalgrass, while a mild increase (albeit not significant) was evident
      in crabgrass. Migration of the fungus seems unlikely in root-free bulk soil, as
      we failed to see transmission when the roots were kept separate. This research is
      the first documentation of non-targeted colonization of this unique root
      symbiotic fungus and highlights the need for such assessments prior to deployment
      of biological organisms in the field.

PMID- 29375606
TI  - Genome-Wide Association Study Identifying Candidate Genes Influencing Important
      Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq.
AB  - Flax (Linum usitatissimum L.) is an important cash crop, and its agronomic traits
      directly affect yield and quality. Molecular studies on flax remain inadequate
      because relatively few flax genes have been associated with agronomic traits or
      have been identified as having potential applications. To identify markers and
      candidate genes that can potentially be used for genetic improvement of crucial
      agronomic traits, we examined 224 specimens of core flax germplasm; specifically,
      phenotypic data for key traits, including plant height, technical length, number
      of branches, number of fruits, and 1000-grain weight were investigated under
      three environmental conditions before specific-locus amplified fragment
      sequencing (SLAF-seq) was employed to perform a genome-wide association study
      (GWAS) for these five agronomic traits. Subsequently, the results were used to
      screen single nucleotide polymorphism (SNP) loci and candidate genes that
      exhibited a significant correlation with the important agronomic traits. Our
      analyses identified a total of 42 SNP loci that showed significant correlations
      with the five important agronomic flax traits. Next, candidate genes were
      screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then
      analyzed by a more stringent screening via co-identification using both a general
      linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at
      least two of the three environments, whereby 15 final candidate genes were
      obtained. Based on these results, we determined that UGT and PL are candidate
      genes for plant height, GRAS and XTH are candidate genes for the number of
      branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits,
      and PHO1 is a candidate gene for the 1000-seed weight. We propose that the
      identified SNP loci and corresponding candidate genes might serve as a biological
      basis for improving crucial agronomic flax traits.

PMID- 29375608
TI  - Long-lasting Corolla Cultivars in Japanese Azaleas: A Mutant AP3/DEF Homolog
      Identified in Traditional Azalea Cultivars from More Than 300 Years Ago.
AB  - Floral shape in higher plants typically requires genetic regulation through MADS
      transcription factors. In Japan, hundreds of azalea cultivars including flower
      shape mutations have been selected from the diversity of endogenous species and
      natural hybrids since the early 17th century, the Edo era (1603-1867). The long
      lasting trait, known as "Misome-sho" in Japanese, has been identified in several
      species and cultivar groups of evergreen azaleas (Rhododendron L.) from three
      hundred years ago in Japan. However, the natural mutation conferring the long
      lasting trait in azalea remains unknown. Here, we showed MADS-box gene mutations
      in long-lasting flowers, R. kaempferi 'Nikko-misome,' R. macrosepalum 'Kocho
      zoroi,' R. indicum 'Chojyu-ho,' and R. * hannoense 'Amagi-beni-chojyu.' All of
      the long-lasting flowers exhibited small-sized corollas with stomata during long
      blooming. In the long-lasting flowers, transcript of the APETALA3 (AP3)/DEFICIENS
      (DEF) homolog was reduced, and an LTR-retrotransposon was independently inserted
      into exons 1, 2, and 7 or an unknown sequence in exon 1 in gDNA of each cultivar.
      This insertion apparently abolished the normal mRNA sequence of the AP3/DEF
      homolog in long-lasting flowers. Also, long-lasting flowers were shown from F2
      hybrids that had homozygous ap3/def alleles. Therefore, we concluded that the
      loss of function of the AP3/DEF homolog through a transposable element insertion
      may confer a stable long-lasting mutation in evergreen azaleas.

PMID- 29375609
TI  - Two Nucleolar Proteins, GDP1 and OLI2, Function As Ribosome Biogenesis Factors
      and Are Preferentially Involved in Promotion of Leaf Cell Proliferation without
      Strongly Affecting Leaf Adaxial-Abaxial Patterning in Arabidopsis thaliana.
AB  - Leaf abaxial-adaxial patterning is dependent on the mutual repression of leaf
      polarity genes expressed either adaxially or abaxially. In Arabidopsis thaliana,
      this process is strongly affected by mutations in ribosomal protein genes and in
      ribosome biogenesis genes in a sensitized genetic background, such as asymmetric
      leaves2 (as2). Most ribosome-related mutants by themselves do not show leaf
      abaxialization, and one of their typical phenotypes is the formation of pointed
      rather than rounded leaves. In this study, we characterized two ribosome-related
      mutants to understand how ribosome biogenesis is linked to several aspects of
      leaf development. Previously, we isolated oligocellula2 (oli2) which exhibits the
      pointed-leaf phenotype and has a cell proliferation defect. OLI2 encodes a
      homolog of Nop2 in Saccharomyces cerevisiae, a ribosome biogenesis factor
      involved in pre-60S subunit maturation. In this study, we found another pointed
      leaf mutant that carries a mutation in a gene encoding an uncharacterized protein
      with a G-patch domain. Similar to oli2, this mutant, named g-patch domain
      protein1 (gdp1), has a reduced number of leaf cells. In addition, gdp1 oli2
      double mutants showed a strong genetic interaction such that they synergistically
      impaired cell proliferation in leaves and produced markedly larger cells. On the
      other hand, they showed additive phenotypes when combined with several known
      ribosomal protein mutants. Furthermore, these mutants have a defect in pre-rRNA
      processing. GDP1 and OLI2 are strongly expressed in tissues with high cell
      proliferation activity, and GDP1-GFP and GFP-OLI2 are localized in the nucleolus.
      These results suggest that OLI2 and GDP1 are involved in ribosome biogenesis. We
      then examined the effects of gdp1 and oli2 on adaxial-abaxial patterning by
      crossing them with as2. Interestingly, neither gdp1 nor oli2 strongly enhanced
      the leaf polarity defect of as2. Similar results were obtained with as2 gdp1 oli2
      triple mutants although they showed severe growth defects. These results suggest
      that the leaf abaxialization phenotype induced by ribosome-related mutations is
      not merely the result of a general growth defect and that there may be a
      sensitive process in the ribosome biogenesis pathway that affects adaxial-abaxial
      patterning when compromised by a mutation.

PMID- 29375610
TI  - Current Knowledge and Computational Techniques for Grapevine Meta-Omics Analysis.
AB  - Growing grapevine (Vitis vinifera) is a key contribution to the economy of many
      countries. Tools provided by genomics and bioinformatics did help researchers in
      obtaining biological knowledge about the different cultivars. Several genetic
      markers for common diseases were identified. Recently, the impact of microbiome
      has been proved to be of fundamental importance both in humans and in plants for
      its ability to confer protection or induce diseases. In this review we report
      current knowledge about grapevine microbiome, together with a description of the
      available computational methodologies for meta-omics analysis.

PMID- 29375611
TI  - Rhizome Fragmentation by Vertical Disks Reduces Elymus repens Growth and Benefits
      Italian Ryegrass-White Clover Crops.
AB  - Tillage controls perennial weeds, such as Elymus repens, partly because it
      fragments their underground storage organs. However, tillage is difficult to
      combine with a growing crop, which limits its application. The aim of this study
      was to evaluate how soil vertical cutting with minimum soil disturbance and
      mowing affect the growth and competitive ability of E. repens in a grass-clover
      crop. A tractor-drawn prototype with vertical disks was used to fragment E.
      repens rhizomes with minimal soil and crop disturbance. In experiments performed
      in 2014 and 2015 at a field site close to Uppsala, Sweden, the rhizomes were
      fragmented before crop sowing (ERF), during crop growth (LRF), or both (ERF+LRF).
      Fragmentation was combined with repeated mowing (yes/no) and four companion crop
      treatments (none, Italian ryegrass, white clover, and grass/clover mixture). The
      results showed that in the grass-clover crop, rhizome fragmentation reduced E.
      repens rhizome biomass production and increased Italian ryegrass shoot biomass.
      ERF and LRF both reduced E. repens rhizome biomass by about 38% compared with the
      control, while ERF+LRF reduced it by 63%. Italian ryegrass shoot biomass was
      increased by 78% by ERF, 170% by LRF and 200% by ERF+LRF. Repeated mowing
      throughout the experiment reduced E. repens rhizome biomass by about 75%.
      Combining repeated mowing with rhizome fragmentation did not significantly
      increase the control effect compared to mowing alone. We concluded that rhizome
      fragmentation using vertical disks can be used both before sowing and during crop
      growth to enhance the controlling effect of grass-clover crops on E. repens.

PMID- 29375612
TI  - Corrigendum: Deep Plant Phenomics: A Deep Learning Platform for Complex Plant
      Phenotyping Tasks.
AB  - [This corrects the article on p. 1190 in vol. 8, PMID: 28736569.].

PMID- 29375614
TI  - Phosphorus Alters Starch Morphology and Gene Expression Related to Starch
      Biosynthesis and Degradation in Wheat Grain.
AB  - Phosphorus is an essential plant macronutrient which profoundly affects the yield
      and quality of wheat starch. In this study, scanning electron microscopy showed
      that P fertilizer amount (0, 46, and 92 kg P ha-1) had no significant effect on
      the shape of starch granules in wheat (cv. Xindong 20) grain. However, confocal
      laser scanning microscopy with 3-(4-carboxybenzoyl) quinoline-2-carboxaldehyde
      and methanolic merbromin stains indicated that P amount influenced the
      microstructure of the starch granules. Starch granules from the 46 kg P ha-1
      treatment released significantly more reducing sugars than those from the 0 and
      92 kg P ha-1 treatments during digestion with alpha-amylase and amyloglucosidase
      digestion. Phosphorus application (especially the 46 kg P ha-1 treatments)
      significantly increased the relative expression of genes related to starch
      synthesis (especially during early to mid-grain filling) and starch degradation
      (especially during mid- and late grain filling). Phosphorus application also
      increased the transcript abundance of amylase genes at the periphery of the
      endosperm. We propose that P application, especially the 46 kg P ha-1 treatment,
      enhanced channels in wheat starch granules. These channels facilitated the
      transport of substances required for starch biosynthesis, thus increasing starch
      accumulation in wheat endosperm. These results provide insight into the potential
      mechanisms through which P influences the microstructure and biosynthesis of
      wheat starch.

PMID- 29375613
TI  - Plant Nucleolar Stress Response, a New Face in the NAC-Dependent Cellular Stress
      Responses.
AB  - The nucleolus is the most prominent nuclear domain, where the core processes of
      ribosome biogenesis occur vigorously. All these processes are finely orchestrated
      by many nucleolar factors to build precisely ribosome particles. In animal cells,
      perturbations of ribosome biogenesis, mostly accompanied by structural disorders
      of the nucleolus, cause a kind of cellular stress to induce cell cycle arrest,
      senescence, or apoptosis, which is called nucleolar stress response. The best
      characterized pathway of this stress response involves p53 and MDM2 as key
      players. p53 is a crucial transcription factor that functions in response to not
      only nucleolar stress but also other cellular stresses such as DNA damage stress.
      These cellular stresses release p53 from the inhibition by MDM2, an E3 ubiquitin
      ligase targeting p53, in various ways, which leads to p53-dependent activation of
      a set of genes. In plants, genetic impairments of ribosome biogenesis factors or
      ribosome components have been shown to cause characteristic phenotypes, including
      a narrow and pointed leaf shape, implying a common signaling pathway connecting
      ribosomal perturbations and certain aspects of growth and development. Unlike
      animals, however, plants have neither p53 nor MDM2 family proteins. Then the
      question arises whether plant cells have a nucleolar stress response pathway. In
      recent years, it has been reported that several members of the plant-specific
      transcription factor family NAC play critical roles in the pathways responsive to
      various cellular stresses. In this mini review, we outline the plant cellular
      stress response pathways involving NAC transcription factors with reference to
      the p53-MDM2-dependent pathways of animal cells, and discuss the possible
      involvement of a plant-unique, NAC-mediated pathway in the nucleolar stress
      response in plants.

PMID- 29375615
TI  - Vegetable Grafting: A Toolbox for Securing Yield Stability under Multiple Stress
      Conditions.

PMID- 29375616
TI  - Retraction: Brassica juncea Lines with Substituted Chimeric GFP-CENH3 Give
      Haploid and Aneuploid Progenies on Crossing with Other Lines.
AB  - [This retracts the article on p. 2019 in vol. 7, PMID: 28111587.].

PMID- 29375618
TI  - Corrigendum: Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel
      Genetic Variants Associated with Age-Related Diseases.
AB  - [This corrects the article on p. 179 in vol. 7, PMID: 27790247.].

PMID- 29375617
TI  - Growth Hormone, Insulin-Like Growth Factor-1, Insulin Resistance, and Leukocyte
      Telomere Length as Determinants of Arterial Aging in Subjects Free of
      Cardiovascular Diseases.
AB  - Background: Increased arterial stiffness (AS), intima-media thickness (IMT), and
      the presence of atherosclerotic plaques (PP) have been considered as important
      aspects of vascular aging. It is well documented that the cardiovascular system
      is an important target organ for growth hormone (GH) and insulin-like growth
      factor (IGF)-1 in humans, and GH /IGF-1 deficiency significantly increases the
      risk for cardiovascular diseases (CVD). The telomere length of peripheral blood
      leukocytes (LTL) is a biomarker of cellular senescence and that has been proposed
      as an independent predictor of (CVD). The aim of this study is to determine the
      role of GH/IGF-1, LTL and their interaction cardiovascular risk factors (CVRF) in
      the vascular aging. Methods: The study group included 303 ambulatory participants
      free of known CVD (104 males and 199 females) with a mean age of 51.8 +/- 13.3
      years. All subjects had one or more CVRF [age, smoking, arterial hypertension,
      obesity, dyslipidemia, fasting hyperglycemia, insulin resistance-HOMA
      (homeostatic model assessment) >2.5, or high glycated hemoglobin]. The study
      sample was divided into the two groups according to age as "younger" (m <= 45
      years, f <= 55 years) and "older" (m > 45 years, f > 55 years). IMT and PP were
      determined by ultrasonography, AS was determined by measuring the carotid-femoral
      pulse wave velocity (c-f PWV) using the SphygmoCor system (AtCor Medical). LTL
      was determined by PCR. Serum IGF-1 and GH concentrations we measured by
      immunochemiluminescence analysis. Results: Multiple linear regression analysis
      with adjustment for CVRF indicated that HOMA, GH, IGF-1, and LTL had an
      independent relationship with all the arterial wall parameters investigated in
      the younger group. In the model with c-f PWV as a dependent variable, p < 0.001
      for HOMA, p = 0.03 for GH, and p = 0.004 for LTL. In the model with IMT as a
      dependent variable, p = 0.0001 for HOMA, p = 0.044 for GH, and p = 0.004 for IGF
      1. In the model with the number of plaques as a dependent variable, p = 0.0001
      for HOMA, and p = 0.045 for IGF-1. In the older group, there were no independent
      significant associations between GH/IGF-1, LTL, HOMA, and arterial wall
      characteristics. Conclusions: GH/IGF-1, IR, HOMA, and LTL were the important
      parameters of arterial aging in younger healthy participants.

PMID- 29375619
TI  - DNA Methylation and Hydroxymethylation in Primary Colon Cancer and Synchronous
      Hepatic Metastasis.
AB  - Colon cancer is one of the most frequent solid tumor and simultaneous diagnosis
      of primary colon cancer and liver metastases occurs in about one fourth of cases.
      The current knowledge on epigenetic signatures, especially those related to
      hydroxymethylation in primary cancer tissue, synchronous metastasis, and blood
      circulating cells is lacking. This study aimed to investigate both methylcytosine
      (mCyt) and hydroxymethylcytosine (hmCyt) status in the DNA of individual patients
      from colon cancer tissue, synchronous liver metastases, and in cancer-free colon
      and liver tissues and leukocytes. Patients undergoing curative surgery (n = 16)
      were enrolled and their laboratory and clinical history data collected. The
      contents of mCyt and hmCyt were determined by a liquid chromatography/mass
      spectrometry (LC/MS/MS) method in DNA extracted from primary colon cancer,
      synchronous hepatic metastatic tissues and homologous cancer-free tissues, i.e.,
      colon and liver tissues as well as leukocytes. The mCyt and hmCyt levels were
      compared between cancerous and cancer-free tissues, and correlations between
      leukocytes and colon/liver tissues for both the mCyt and hmCyt levels were
      evaluated. The mCyt levels were similar in primary colon cancer and liver
      metastasis tissues (4.69 +/- 0.37% vs. 4.77 +/- 0.38%, respectively, p = 0.535),
      and both primary and metastatic tissues were hypomethylated compared to cancer
      free colon (4.98 +/- 0.26%). The difference in the mCyt content between cancerous
      and cancer-free colon tissues was significantly lower in primary colon cancer (p
      = 0.004), but not in liver metastasis (p = 0.148). The hmCyt content was similar
      in primary colon cancer compared to liver metastasis (0.035%, C.I. 0.024-0.052%
      versus 0.035%, C.I. 0.021-0.058%, respectively, p = 0.905) and markedly depleted
      compared to the cancer-free colon (0.081%, C.I. 0.055-0.119%) with a
      statistically significant difference (p < 0.05) for both comparisons. The mCyt
      levels showed a borderline correlation between leukocytes and colon cancer tissue
      (Pearson's correlation coefficient = 0.51, p = 0.052) while no correlations were
      detected for the hmCyt levels. In conclusion, primary colon cancer and
      synchronous liver metastasis tissues showed a similar epigenetic status but were
      significantly hypomethylated and hypohydroxymethylated as compared to homologous
      cancer-free colon tissues.

PMID- 29375620
TI  - Preoperative Anaemia and Associated Postoperative Outcomes in Noncardiac Surgery
      Patients in Central Region of Ghana.
AB  - Introduction: Several studies suggest that preoperative anaemia (PA) is
      associated with adverse postoperative outcomes, but little is known about these
      outcomes in the Central Region of Ghana. This study aims to determine the
      prevalence of PA among noncardiac surgical patients and its implications for
      their postoperative outcomes. Methods: This study was designed as an
      observational study; data including demographics and clinical and laboratory
      results were collected from the patients' records and through interviews.
      Results: A total of 893 inpatient surgical cases undergoing elective and
      emergency operations, aged 15 years and above with mean age of 44.2 +/- 17.0 yrs,
      were enrolled. The prevalence of PA was 54.3%, mostly microcytic with or without
      hypochromia (57.2%). The prevalence was higher in females than males (p <=
      0.001). Preoperative anaemia was significantly associated with prolonged length
      of hospital stay (OR: 2.12 (95% CI: 1.49-3.10)). Allogeneic blood transfusion
      significantly prolonged the length of hospital stay (OR 4.48 (95% CI: 2.67
      7.51)). 15.5% of the anaemic patients received oral iron supplements compared to
      2.2% of nonanaemic patients (p <= 0.001). Conclusion: Preoperative anaemia is
      common among noncardiac surgical patients. It is independently and significantly
      associated with prolonged hospital stay leading to the use of increased
      healthcare resources. It is also the main predictor for perioperative allogeneic
      blood transfusions and the use of haematinics.

PMID- 29375621
TI  - Molecular Genetic Analysis of Human Endometrial Mesenchymal Stem Cells That
      Survived Sublethal Heat Shock.
AB  - High temperature is a critical environmental and personal factor. Although heat
      shock is a well-studied biological phenomenon, hyperthermia response of stem
      cells is poorly understood. Previously, we demonstrated that sublethal heat shock
      induced premature senescence in human endometrial mesenchymal stem cells (eMSC).
      This study aimed to investigate the fate of eMSC-survived sublethal heat shock
      (SHS) with special emphasis on their genetic stability and possible malignant
      transformation using methods of classic and molecular karyotyping, next
      generation sequencing, and transcriptome functional analysis. G-banding revealed
      random chromosome breakages and aneuploidy in the SHS-treated eMSC. Molecular
      karyotyping found no genomic imbalance in these cells. Gene module and protein
      interaction network analysis of mRNA sequencing data showed that compared to
      untreated cells, SHS-survived progeny revealed some difference in gene
      expression. However, no hallmarks of cancer were found. Our data identified
      downregulation of oncogenic signaling, upregulation of tumor-suppressing and
      prosenescence signaling, induction of mismatch, and excision DNA repair. The
      common feature of heated eMSC is the silence of MYC, AKT1/PKB oncogenes, and
      hTERT telomerase. Overall, our data indicate that despite genetic instability,
      SHS-survived eMSC do not undergo transformation. After long-term cultivation,
      these cells like their unheated counterparts enter replicative senescence and
      die.

PMID- 29375622
TI  - The Application of Stem Cells from Different Tissues to Cartilage Repair.
AB  - The degeneration of articular cartilage represents an ongoing challenge at the
      clinical and basic level. Tissue engineering and regenerative medicine using
      stem/progenitor cells have emerged as valid alternatives to classical reparative
      techniques. This review offers a brief introduction and overview of the field,
      highlighting a number of tissue sources for stem/progenitor cell populations.
      Emphasis is given to recent developments in both clinical and basic sciences. The
      relative strengths and weaknesses of each tissue type are discussed.

PMID- 29375624
TI  - Cell Therapy for Refractory Angina: A Reappraisal.
AB  - Cardiac cell-based therapy has emerged as a novel therapeutic option for patients
      dealing with untreatable refractory angina (RA). However, after more than a
      decade of controlled studies, no definitive consensus has been reached regarding
      clinical efficacy. Although positive results in terms of surrogate endpoints have
      been suggested by early and phase II clinical studies as well as by meta
      analyses, the more recent reports lacked the provision of definitive response in
      terms of hard clinical endpoints. Regrettably, pivotal trials designed to
      conclusively determine the efficacy of cell-based therapeutics in such a
      challenging clinical condition are therefore still missing. Considering this, a
      comprehensive reappraisal of cardiac cell-based therapy role in RA seems
      warranted and timely, since a number of crucial cell- and patient-related aspects
      need to be systematically analysed. As an example, the large variability in
      efficacy endpoint selection appears to be a limiting factor for the advancement
      of cardiac cell-based therapy in the field. This review will provide an overview
      of the key elements that may have influenced the results of cell-based trials in
      the context of RA, focusing in particular on the understanding at which the
      extent of angina-related endpoints may predict cell-based therapeutic efficacy.

PMID- 29375623
TI  - Nanotechnology-Based Cardiac Targeting and Direct Cardiac Reprogramming: The
      Betrothed.
AB  - Cardiovascular diseases represent the first cause of morbidity in Western
      countries, and chronic heart failure features a significant health care burden in
      developed countries. Efforts in the attempt of finding new possible strategies
      for the treatment of CHF yielded several approaches based on the use of stem
      cells. The discovery of direct cardiac reprogramming has unveiled a new approach
      to heart regeneration, allowing, at least in principle, the conversion of one
      differentiated cell type into another without proceeding through a pluripotent
      intermediate. First developed for cancer treatment, nanotechnology-based
      approaches have opened new perspectives in many fields of medical research,
      including cardiovascular research. Nanotechnology could allow the delivery of
      molecules with specific biological activity at a sustained and controlled rate in
      heart tissue, in a cell-specific manner. Potentially, all the mediators and
      structural molecules involved in the fibrotic process could be selectively
      targeted by nanocarriers, but to date, only few experiences have been made in
      cardiac research. This review highlights the most prominent concepts that
      characterize both the field of cardiac reprogramming and a nanomedicine-based
      approach to cardiovascular diseases, hypothesizing a possible synergy between
      these two very promising fields of research in the treatment of heart failure.

PMID- 29375626
TI  - Producing Stem Cell-Based Transplants for Future Therapeutic Purposes.

PMID- 29375625
TI  - Effect of Uniaxial Tensile Cyclic Loading Regimes on Matrix Organization and
      Tenogenic Differentiation of Adipose-Derived Stem Cells Encapsulated within 3D
      Collagen Scaffolds.
AB  - Adipose-derived mesenchymal stem cells have become a popular cell choice for
      tendon repair strategies due to their relative abundance, ease of isolation, and
      ability to differentiate into tenocytes. In this study, we investigated the solo
      effect of different uniaxial tensile strains and loading frequencies on the
      matrix directionality and tenogenic differentiation of adipose-derived stem cells
      encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%,
      2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7
      day period using a custom-built uniaxial tensile strain bioreactor were
      characterized in terms of matrix organization, cell viability, and
      musculoskeletal gene expression profiles. The results displayed that the collagen
      fibers of the loaded samples exhibited increased matrix directionality with an
      increase in strain values. Gene expression analyses demonstrated that ASC
      encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed
      significant increases in extracellular matrix genes and tenogenic differentiation
      markers. Importantly, no cross-differentiation potential to osteogenic,
      chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz
      frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified
      as the appropriate mechanical loading regime to induce tenogenic differentiation
      of adipose-derived stem cells cultured in a three-dimensional environment.

PMID- 29375627
TI  - Shared Care for Suicidal Youth.

PMID- 29375628
TI  - Improving Access to Child and Adolescent Mental Health Care: The Choice and
      Partnership Approach.
AB  - Objective: The Choice and Partnership Approach (CAPA) is designed to improve
      access and quality of pediatric mental health care. We tested whether CAPA
      improved access in an academic pediatric hospital. Method: We used de-identified
      administrative data to compare access pre- (2011) and post-CAPA (2013). Results:
      Wait time to first appointment in 2011 was 225.3 days (95% CI = [211.0, 239.6], N
      = 364), compared to 93.0 days (95% CI = [89.2, 96.8], N = 838) in 2013 (p<.001).
      Mean wait time between the first and second appointments was 59.2 days (95% CI =
      [46.5, 71.9], N = 86) in 2011, compared to 95.9 days (95% CI = [90.3, 101.5], N =
      487) in 2013 (p < .001). However, overall mean wait time from referral to second
      appointment decreased from 271.2 days (95% CI = [236.5, 305.9], N = 86) in 2011
      to 168.9 days (95% CI = [161.6, 176.2], N = 487) in 2013 (p < .001). Provider
      productivity increased from 32.6 to 57.0 first appointments/FTE/year. Depending
      on the question, 65 to 95% of parents and children gave positive answers about
      CAPA. Conclusions: CAPA implementation was associated with more patients served,
      decreased waiting time to first appointment, and higher productivity.

PMID- 29375629
TI  - Clinical Utility of Screening for Anxiety and Depression in Children with
      Tourette Syndrome.
AB  - Background: Tourette syndrome (TS) is often co-morbid with attention deficit
      hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). Studies of
      TS, anxiety and depression have found variable results depending on study
      methodology and sample characteristics. Our aim was to examine the clinical
      utility of routine screening for anxiety and depression in children with TS.
      Methods: Using a clinic-based sample, we evaluated the proportion of children
      with TS meeting diagnostic criteria for ADHD, OCD, generalized anxiety disorder
      (GAD), separation anxiety disorder (SAD), and major depressive disorder (MDD);
      the frequency of above average anxiety and depressive symptoms using the
      Multidimensional Anxiety Scale for Children (MASC) and the Children's Depression
      Inventory (CDI); and the association between diagnoses and symptom severity.
      Results: One hundred twenty six children were included (mean age 10.7 years). The
      most common comorbid disorder was ADHD (37%), followed by GAD (21%), OCD (10%),
      MDD (2%) and SAD (2%). On the MASC, the separation anxiety/panic subscale score
      was higher than all other subscale scores (p<0.0001). Clinically significant
      anxiety symptoms were present in 20% of the sample based on the MASC Anxiety
      Disorders Index, while 6% were identified as potentially clinically depressed
      based on the CDI Total Score. Yale Global Tic Severity Scale scores were
      positively correlated with total scores on the MASC (r=0.22, p=0.03) and CDI
      (r=0.37, p=0.0002). Conclusions: Routine screening children with TS for anxiety
      is warranted given the rate of comorbidity. Screening for depression in TS will
      have a higher yield in adolescents, adults, and children with more severe tics.

PMID- 29375630
TI  - Youths' Experiences of School Re-Integration Following Psychiatric
      Hospitalization.
AB  - Objective: The purpose of this study was to report youths' experiences of school
      re-integration post-discharge from psychiatric hospital. No reports of school
      reintegration from the patient perspective could be located; hence, a second
      objective was to explore school-related and clinical factors associated with
      youth who reported an unfavourable school re-integration experiences. Methods:
      Patients were recruited while in hospital for acute psychiatric care. They
      provided informed consent to be contacted post discharge regarding their
      perceptions of their school reintegration experience. About ten weeks after
      discharge youth were surveyed via telephone (n=40) or online (n=22) surveys.
      Results: Of the 121 youth who agreed to be contacted after discharge, 62 youth
      completed the post-discharge survey. Almost half (n=29) of the youth reported
      that they had considerable difficulty with school reintegration. Youth reported
      managing social situations, academic pressures and emotions as substantial
      problems. Youth who reported a negative transition experience had significantly
      worse scores on self-reported Total and emotion subscale of the Strength and
      Difficulties Questionnaire, and concern about the impact of emotions on school re
      entry, and significantly less psychiatrist-reported improvement than youth who
      reported a neutral or positive transition experience. There were no differences
      between the two groups on school-related variables. Youth with prior admission
      reported greater difficulties with peers and significantly worse clinical factors
      than youth without prior admissions. Conclusions: High emotional difficulty
      scores and concern about the impact of emotions on reintegration prior to
      discharge distinguished youths with negative school reintegration experiences.
      These patients may benefit from greater assistance with managing their emotional
      problems, and coping and social skills training before and during school
      reintegration.

PMID- 29375631
TI  - Emergency Department Referrals for Adolescent Urgent Psychiatric Consultation:
      Comparison of Clinical Characteristics of Repeat-presentations and Single
      presentation.
AB  - Objective: a) to examine the demographic and clinical characteristics of repeat
      presentations to an adolescent urgent psychiatric clinic, and b) to compare them
      with single-time presentation. Method: This 18-month retrospective study compared
      repeat-presenters to age and gender matched single-time presenters. Demographic
      variables included age gender and ethnicity. Clinical variables included reason
      for referral, family history, diagnosis, recommendations and compliance. Data
      were analyzed using descriptive statistics, McNemar's Chi-square tests for
      matched pairs, and conditional logistic regression. Results: Of 624 assessments
      24% (N=151) were repeat-presentations. Compared with single-presentation, repeat
      presentation group had a higher proportion of Aboriginal youth (X2 (1) = 108.28 p
      < 0.01), a higher proportion in special educational placement (X2 (1) = 6.82, p <
      0.01), a higher proportion with a family history of anxiety disorders (X2 (1) =
      10.62, p = 0.01) and substance use disorder (X2 (1) = 18.99, p < 0.01).
      Conditional logistic regression results suggested that repeat-presentation group
      had higher odds of past hospital admission (OR: 3.50, p < 0.01) higher odds of
      family history of mood disorders (OR: 4.86, p < 0.01) and of antisocial disorders
      (OR: 4.97, p = 0.02), and lower odds of recommendation compliance (OR: 0.10, p <
      0.01). Conclusion: Repeat-presentations for urgent psychiatric consultation
      constitute a quarter of referrals to the urgent psychiatric clinic. Identifying
      and addressing factors that contribute to repeat-presentations may, assist in
      improving treatment compliance by ensuring focused interventions and service
      delivery for these youth. In turn, this will improve access to the limited urgent
      services for other youth.

PMID- 29375632
TI  - The Experience of Psychiatric Care of Adolescents with Anxiety-based School
      Refusal and of their Parents: A Qualitative Study.
AB  - Objective: Anxiety-based school refusal in adolescence is a complex, sometimes
      difficult to treat disorder that can have serious academic and psychiatric
      consequences. The objective of this qualitative study was to explore how teens
      with this problem and their parents experience the psychiatric care received.
      Methods: This qualitative multicenter study took place in France, where we
      conducted semi-structured interviews with adolescents receiving psychiatric care
      for anxiety-based school refusal and with their parents. Data collection by
      purposive sampling continued until we reached theoretical sufficiency. Data
      analysis was thematic. Results: This study included 20 adolescents aged 12 to 18
      years and 21 parents. Two themes emerged from the analysis: (1) the goals of
      psychiatric care with two sub-themes, "self-transformation" and problem solving;
      and, (2) the therapeutic levers identified as effective with two sub-themes: time
      and space and relationships. Conclusion: Our results show a divergence between
      parents and teens in their representations of care and especially of its goals.
      Therapeutic and research implications about the terms of return to school within
      psychiatric care and also the temporality of care are discussed.

PMID- 29375633
TI  - Open Trial of Family-Based Treatment of Anorexia Nervosa for Transition Age
      Youth.
AB  - Objective: This pilot study conducted an open trial of a manualized adaptation to
      Family-Based Treatment for Transition Age Youth (FBT-TAY) for Anorexia Nervosa
      (AN). The aims were: (1) determine the acceptability of FBT for TAY; and, (2)
      establish preliminary effect sizes for the impact of FBT-TAY on eating disorder
      behaviour and weight restoration. Method: Twenty-six participants across two
      paediatric and one adult hospital site were recruited to participate.
      Participants completed the Eating Disorder Examination Questionnaire (EDE-Q) at
      the start of treatment, the end-of-treatment, and three-month follow-up. Results:
      FBT-TAY is an acceptable and feasible treatment to all study therapists as
      evidenced by their fidelity to the model. FBT-TAY is a feasible and acceptable
      intervention to transition age youth, given only 27.27% chose treatment as usual
      over FBT-TAY. Participants presented significant improvement at end-of-treatment
      and three-months post-treatment (p < .001; ES = 0.34) from baseline on the EDE-Q
      Global Score. Participants also achieved and maintained weight restoration at the
      end-of-treatment and three-months post-treatment when compared to baseline (p <
      .0001, ES = 0.54). Conclusions: FBT-TAY, the first manualized AN treatment for
      TAY, demonstrated feasibility and acceptability with therapists and participants
      as well as improvement for participants in EDE-Q global score and weight. Given
      the current dearth of effective treatments for TAY with AN, FBT-TAY is a
      promising adaptation of FBT. A larger clinical trial with a 12-month follow-up is
      recommended.

PMID- 29375634
TI  - Returning to Stimulants in Children with Treatment Resistant ADHD: A Case Series.
AB  - Objective: To present a case series of children retrialed on stimulants after
      initial poor stimulant responses given the paucity of information on the
      usefulness of this strategy. Methods: Health records from an ADHD medication
      service were obtained for six children who: (i) were medication naive at service
      entry; (ii) had trials of at least one stimulant from each stimulant class; (iii)
      subsequently received a non-stimulant ADHD medication; and, (iv) were then
      retried on stimulants. Results: Initial stimulant discontinuation was a function
      of adverse effects and/or limited symptom improvement. Minimal response and/or
      adverse effects to non-stimulants contributed to the decision to retry
      stimulants. Final ADHD symptom ratings by parents and teachers were significantly
      better than baseline for this cohort. Three were discharged on stimulants, two as
      monotherapy. Conclusion: Further study is required to develop evidence-based
      treatment algorithms for treatment resistant ADHD. Retrying a stimulant may be
      one option.

PMID- 29375635
TI  - Comparing Self-Concept Among Youth Currently Receiving Inpatient Versus
      Outpatient Mental Health Services.
AB  - Objective: This study compared levels of self-concept among youth who were
      currently receiving inpatient versus outpatient mental health services. Method:
      Forty-seven youth were recruited from the Child & Youth Mental Health Program at
      McMaster Children's Hospital. Self-concept was measured using the Self-Perception
      Profile for Children and Adolescents. Results: The mean age was 14.5 years and
      most participants were female (70.2%). ANOVAs comparing self-concept with
      population norms showed large significant effects (d = 0.77 to 1.93) indicating
      compromised self-concept among youth receiving mental health services. Regression
      analyses controlling for patient age, sex, family income, and diagnoses of major
      depressive disorder, generalized social phobia, and generalized anxiety showed
      that the inpatient setting was a significant predictor of lower global self-worth
      (beta=-.26; p=.035). Conclusions: Compared to outpatients, inpatients generally
      reported lower self-concept, but differences were significant only for global
      self-worth. Future research replicating this finding and assessing its clinical
      significance is encouraged.

PMID- 29375637
TI  - INSTRUCTIONS DESTINEES AUX AUTEURS.

PMID- 29375638
TI  - Comparative Researches of Semen Arecae and Charred Semen Arecae on
      Gastrointestinal Motility, Motilin, Substance P, and CCK in Chronically Stressed
      Rats.
AB  - Aims: To compare the effects of Semen Arecae (SA) and Charred Semen Arecae (CSA)
      on gastrointestinal motility, motilin, substance P (SP), and cholecystokinin
      (CCK) in chronically stressed rats. Methods: Rats were randomly divided into
      control group and stress group. Rats in stress group were randomly exposed to a
      variety of unpredictable stimulations for 21 days. Then, the rats were treated
      orally with distilled water, SA, CSA, and mosapride for 7 days. Gastric residue
      rate and intestinal propulsion rate were evaluated. Serum levels of motilin and
      SP were measured by enzyme-linked immunosorbent assay (ELISA). CCK mRNA was
      quantified by using quantitative real-time PCR (qRT-PCR). Results: Both SA and
      CSA improved the intestinal propulsion and reduced the gastric residue in
      chronically stressed rats. Furthermore, the serum levels of motilin and SP were
      significantly higher and the CCK mRNA expressions in intestine and hypothalamus
      were downregulated in SA and CSA groups. Furthermore, it was found that CSA is
      more effective. Conclusion: Both SA and CSA enhanced gastrointestinal motility
      and increased serum levels of motilin and SP in chronically stressed rats via
      downregulating CCK mRNA expressions in intestine and hypothalamus. Importantly,
      CSA possessed more effective promoting effects.

PMID- 29375639
TI  - Effects of the Aqueous Extract from Tabebuia roseoalba and Phenolic Acids on
      Hyperuricemia and Inflammation.
AB  - Tabebuia species (Bignoniaceae) have long been used in folk medicine as anti
      inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study
      was to investigate if aqueous extract from the leaves (AEL) of Tabebuia roseoalba
      (Ridl.) Sandwith, Bignoniaceae, and its constituents could be useful to decrease
      serum uric acid levels and restrain the gout inflammatory process. HPLC analysis
      identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects
      and inhibition of liver XOD (xanthine oxidoreductase) by AEL and identified
      compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was
      evaluated on MSU (monosodium urate) crystal-induced paw edema. In addition, AEL
      antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids
      were able to reduce serum uric acid levels in hyperuricemic mice probably through
      inhibition of liver xanthine oxidase activity and significantly decreased the paw
      edema induced by MSU crystals. AEL showed significant antioxidant activity in all
      evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a
      promising agent for treatment for gout and inflammatory diseases. We suggest that
      caffeic and chlorogenic acids may be responsible for the activities demonstrated
      by the species.

PMID- 29375640
TI  - Study on Quality Standard of Processed Curcuma Longa Radix.
AB  - To control the quality of Curcuma Longa Radix by establishing quality standards,
      this paper increased the contents of extract and volatile oil determination.
      Meanwhile, the curcumin was selected as the internal marker, and the relative
      correlation factors (RCFs) of demethoxycurcumin and bisdemethoxycurcumin were
      established by high performance liquid chromatography (HPLC). The contents of
      multicomponents were calculated based on their RCFs. The rationality and
      feasibility of the methods were evaluated by comparison of the quantitative
      results between external standard method (ESM) and quantitative analysis of
      multicomponents by single-marker (QAMS). Ethanol extracts ranged from 9.749 to
      15.644% and the mean value was 13.473%. The volatile oil ranged from 0.45 to 0.90
      mL/100 g and the mean value was 0.66 mL/100 g. This method was accurate and
      feasible and could provide a reference for further comprehensive and effective
      control of the quality standard of Curcuma Longa Radix and its processed
      products.

PMID- 29375641
TI  - The Effects of Aromatherapy on Intensive Care Unit Patients' Stress and Sleep
      Quality: A Nonrandomised Controlled Trial.
AB  - Background: Stress has both physiological and psychological effects and can
      negatively impact patients' treatment and recovery. We examined whether the
      aromatherapy alleviated patients' stress and improved their sleep quality and
      provided data that can be utilized in clinical settings. Methods: This was a
      nonrandomised controlled experimental study. Participants included lucid adult
      patients who were admitted to the intensive care unit and had spent more than two
      nights there. The experimental treatment required participants to engage in deep
      breathing with essential oils as part of the aromatherapy. The control group was
      instructed to go to sleep without receiving the lavender aroma oil. Results: The
      experimental group and control group showed a significant difference in perceived
      stress (F = 60.11, p < .001), objective stress index (F = 25.65, p < .001),
      systolic blood pressure (F = 9.09, p < .001), diastolic blood pressure (F = 2.47,
      p = .046), heart rate (F = 5.71, p < .001), and sleep quality (F = 109.46, p <
      .001). Conclusions: The results revealed that aromatherapy alleviated stress and
      improved sleep quality in intensive care unit patients after 2 days of the
      experimental treatment. These results demonstrate that aromatherapy affects
      stress and sleep quality, thus indicating its value in nursing interventions.
      This trial is registered with KCT0002344.

PMID- 29375642
TI  - In Vitro Control of Uropathogenic Microorganisms with the Ethanolic Extract from
      the Leaves of Cochlospermum regium (Schrank) Pilger.
AB  - The roots of Cochlospermum regium, popularly known as "algodaozinho-do-cerrado,"
      are used for the treatment of genitourinary infections. However, the removal of
      their subterranean structures results in the death of the plant, and the use of
      the leaves becomes a viable alternative. Therefore, the antimicrobial activity of
      Cochlospermum regium leaf's ethanolic extract and its action on the biofilm
      formation of microorganisms associated with urinary infection were evaluated. The
      total phenolic compounds, flavoids, and tannins were quantified using the
      reagents Folin-Ciocalteu, aluminum chloride, and vanillin, respectively. The
      antimicrobial activity was evaluated by the broth microdilution method and the
      effect of the extract in the biofilm treatment was measured by the drop plate
      method. Cytotoxicity was evaluated by the method based on the reduction of MTS
      and the mutagenicity by the Ames test. The ethanolic extract of C. regium leaves
      presented 87.4 mg/EQ of flavonoids, 167.2 mg/EAG of total phenolic compounds, and
      21.7 mg/ECA of condensed tannins. It presented reduction of the biofilm formation
      for E. coli and C. tropicalis and antimicrobial action of 1 mg/mL and 0.5 mg/mL,
      respectively. The extract showed no cytotoxicity and mutagenicity at the
      concentrations tested. This study demonstrated that C. regium leaves are a viable
      option for the treatment of genitourinary infections and for the species
      preservation.

PMID- 29375643
TI  - Experimental Study on the Expression of IL-1beta and bFGF in Wound Healing
      Process of Rabbit Cutaneous Infective Wound in Liu-He-Dan.
AB  - Objective: This study applied Liu-He-Dan (LHD) to treat the infective wounds of
      rabbits to explore the mechanism of LHD in promoting wound healing. Method: Five
      circular infective incisions were generated on the back of each rabbit. Wound
      dressings were performed every day since postoperative day 1. Ten rabbits were
      euthanized on days 3, 7, 14, and 21. Each specimen was divided into two parts,
      one was used for detecting interleukin-1 beta (IL-1beta), and the other one was
      used for detecting basic fibroblast growth factor (bFGF). Result: The content of
      IL-1beta in the model group was higher than those in the other groups (P < 0.05).
      The content of IL-1beta in the treatment group was lower than the other groups on
      days 14 and 21. The expression of bFGF in treatment group is significant on days
      3, 7, and 14, compared with traditional Chinese medicine group and model group.
      The expression of bFGF has no significant difference with Western group.
      Conclusion: The research approved that LHD could specifically suppress the
      expression of IL-1beta and upregulate the expression of bFGF in the wound,
      decreasing the release of inflammatory factor of the infective wounds and
      promoting the healing of the infective wounds.

PMID- 29375644
TI  - Urinary and Serum Metabolomics Analyses Uncover That Total Glucosides of Paeony
      Protect Liver against Acute Injury Potentially via Reprogramming of Multiple
      Metabolic Pathways.
AB  - Total glucosides of paeony (TGP) have been confirmed to be hepatoprotective.
      However, the underlying mechanism is largely unclear. In this study, we
      investigated the metabolic profiles of urine and serum in rats with carbon
      tetrachloride- (CCl4-) induced experimental liver injury and TGP administration
      by using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The
      vehicle or a single dose of TGP was intragastrically administered to Wistar rats
      once a day for 14 consecutive days. To induce ALI, 50% CCl4 was injected
      intraperitoneally into these rats 2 hours after the last time administration of
      saline of TGP at the 14th day. The results indicated that TGP administration
      could protect rats from CCl4-induced ALI and alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) elevation, as well as hepatocyte apoptosis and
      inflammation. Furthermore, metabolomics analysis showed that TGP treatment
      significantly attenuated CCl4-triggered deregulation of multiple metabolites in
      both urine and serum, including glycine, alanine, proline, and glutamine.
      Metabolite set enrichment and pathway analyses demonstrated that amino acid
      cycling and glutathione metabolism were two main pathways involved in CCl4
      induced experimental liver injury and TGP administration. Taken together, these
      findings revealed that regulation of metabolites potentially plays a pivotal role
      in the protective effect of TGP on ALI.

PMID- 29375645
TI  - N-Butanol and Aqueous Fractions of Red Maca Methanolic Extract Exerts Opposite
      Effects on Androgen and Oestrogens Receptors (Alpha and Beta) in Rats with
      Testosterone-Induced Benign Prostatic Hyperplasia.
AB  - Benign Prostatic Hyperplasia (BPH) affects, worldwide, 50% of 60-year-old men.
      The Peruvian plant red maca (Lepidium meyenii) inhibits BPH in rodents. This
      study aimed to determine the effects of methanolic red maca extract and its n
      butanol and aqueous fractions on expression of androgen and oestrogen receptors
      in rats with testosterone enanthate-induced BPH. Thirty-six rats in six groups
      were studied. Control group received 2 mL of vehicle orally and 0.1 mL of
      propylene glycol intramuscularly. The second group received vehicle orally and
      testosterone enanthate (TE) (25 mg/0.1 mL) intramuscularly in days 1 and 7. The
      other four groups were BPH-induced with TE and received, during 21 days, 3.78
      mg/mL of finasteride, 18.3 mg/mL methanol extract of red maca, 2 mg/mL of n
      butanol fraction, or 16.3 mg/mL of aqueous fraction from red maca. Treatments
      with red maca extract and its n-butanol but not aqueous fraction reduced prostate
      weight similar to finasteride. All maca treated groups restored the expression of
      ERbeta, but only the aqueous fraction increased androgen receptors and ERalpha.
      In conclusion, butanol fraction of red maca reduced prostate size in BPH by
      restoring expression of ERbeta without affecting androgen receptors and ERalpha.
      This effect was not observed with aqueous fraction of methanolic extract of red
      maca.

PMID- 29375647
TI  - The use of plant models in deep learning: an application to leaf counting in
      rosette plants.
AB  - Deep learning presents many opportunities for image-based plant phenotyping. Here
      we consider the capability of deep convolutional neural networks to perform the
      leaf counting task. Deep learning techniques typically require large and diverse
      datasets to learn generalizable models without providing a priori an engineered
      algorithm for performing the task. This requirement is challenging, however, for
      applications in the plant phenotyping field, where available datasets are often
      small and the costs associated with generating new data are high. In this work we
      propose a new method for augmenting plant phenotyping datasets using rendered
      images of synthetic plants. We demonstrate that the use of high-quality 3D
      synthetic plants to augment a dataset can improve performance on the leaf
      counting task. We also show that the ability of the model to generate an
      arbitrary distribution of phenotypes mitigates the problem of dataset shift when
      training and testing on different datasets. Finally, we show that real and
      synthetic plants are significantly interchangeable when training a neural network
      on the leaf counting task.

PMID- 29375646
TI  - Estimated dietary iodine intake as a predictor of placental size: evidence from
      the ELSPAC study.
AB  - Background: The relationship between low iodine status and pregnancy-associated
      comorbidities has been known for decades. The relationship between iodine intake
      and placental pathologies is, however, far less clear. This study was designed to
      examine the relationship between dietary iodine intake and placental size while
      also focusing on typical adverse pregnancy outcomes. Method: The dietary iodine
      intake of 4711 pregnant women enrolled in the Czech part of the European
      Longitudinal Study of Pregnancy and Childhood (ELSPAC) in 1990-1991 was
      established using a 145-item food frequency questionnaire. Multivariate linear
      regression models were used to estimate the relationship between dietary iodine
      intake during pregnancy and placental weight. Additional models were constructed
      to investigate the relationship between estimated dietary iodine intake and
      adverse birth outcomes. Results: The estimated average iodine intake in the
      ELSPAC cohort was 106.6 MUg/day. In the fully adjusted model, estimated dietary
      iodine intake was found to be significantly negatively associated with placental
      weight (beta = -0.025, 95% CI: -0.044; -0.006, p = 0.011). Moreover, estimated
      dietary iodine intake was found to be significantly positively associated with
      the birth weight / placental weight ratio in the fully adjusted model (beta = 
      0.024, 95% CI: 0.004; 0.043, p = 0.016). Conclusions: This study provides
      evidence of a relationship between estimated dietary iodine intake and placental
      weight and the birth weight / placental weight ratio. Additional research is
      warranted to provide more insight into the role of iodine in early as well as
      late placentation.

PMID- 29375648
TI  - Improved non-destructive 2D and 3D X-ray imaging of leaf venation.
AB  - Background: Leaf venation traits are important for many research fields such as
      systematics and evolutionary biology, plant physiology, climate change, and
      paleoecology. In spite of an increasing demand for vein trait data, studies are
      often still data-limited because the development of methods that allow rapid
      generation of large sets of vein data has lagged behind. Recently, non
      destructive X-ray technology has proven useful as an alternative to traditional
      slow and destructive chemical-based methods. Non-destructive techniques more
      readily allow the use of herbarium specimens, which provide an invaluable but
      underexploited resource of vein data and related environmental information. The
      utility of 2D X-ray technology and microfocus X-ray computed tomography, however,
      has been compromised by insufficient image resolution. Here, we advanced X-ray
      technology by increasing image resolution and throughput without the application
      of contrast agents. Results: For 2D contact microradiography, we developed a
      method which allowed us to achieve image resolutions of up to 7 um, i.e. a 3.6
      fold increase compared to the industrial standard (25 um resolution). Vein
      tracing was further optimized with our image processing standards that were
      specifically adjusted for different types of leaf structure and the needs of
      higher imaging throughput. Based on a test dataset, in 91% of the samples the 7
      um approach led to a significant improvement in estimations of minor vein density
      compared to the industrial standard. Using microfocus X-ray computed tomography,
      very high-resolution images were obtained from a virtual 3D-2D transformation
      process, which was superior to that of 3D images. Conclusions: Our 2D X-ray
      method with a significantly improved resolution advances rapid non-destructive
      bulk scanning at a quality that in many cases is sufficient to determine key
      venation traits. Together with our high-resolution microfocus X-ray computed
      tomography method, both non-destructive approaches will help in vein trait data
      mining from museum collections, which provide an underexploited resource of
      historical and recent data on environmental and evolutionary change. In spite of
      the significant increase in effective image resolution, a combination of high
      throughput and full visibility of the vein network (including the smallest veins
      and their connectivity) remains challenging, however.

PMID- 29375649
TI  - High-throughput analysis of amino acids in plant materials by single quadrupole
      mass spectrometry.
AB  - Background: The amino acid profile of plants is an important parameter in
      assessments of their growth potential, resource-use efficiency and/or quality as
      food and feed. Screening studies may involve large number of samples but the
      classical amino acid analysis is limited by the fact that it is very time
      consuming with typical chromatographic run times of 70 min or more. Results: We
      have here developed a high-throughput method for analysis of amino acid profiles
      in plant materials. The method combines classical protein hydrolysis and
      derivatization with fast separation by UHPLC and detection by a single quadrupole
      (QDa) mass spectrometer. The chromatographic run time is reduced to 10 min and
      the precision, accuracy and sensitivity of the method are in line with other
      recent methods utilizing advanced and more expensive mass spectrometers. The
      sensitivity of the method is at least a factor 10 better than that of methods
      relying on detection by fluorescence or UV. It is possible to downscale sample
      size to 20 mg without compromising reproducibility, which makes the method ideal
      for analysis of very small sample amounts. Conclusion: The developed method
      allows high-throughput analysis of amino acid profiles in plant materials. The
      analysis is robust and accurate as well as compatible with both free amino acids
      and protein hydrolysates. The QDa detector offers high sensitivity and accuracy,
      while at the same time being relatively simple to operate and cheap to purchase,
      thus significantly reducing the overall analytical costs compared to methods
      based on more advanced mass spectrometers.

PMID- 29375650
TI  - Molecular Adsorbent Recirculating System as a Diagnostic and Therapeutic
      Modality.
AB  - Despite the many advancements in liver transplantation (LT), mortality in
      patients with hepatic failure remains high, and to date, many patients die while
      awaiting LT. The molecular adsorbent recirculating system (MARS(r)) is an
      extracorporeal liver support system intended to provide short-term metabolic
      detoxification, often as a vital bridge to LT. We report the case of a 41-year
      old non-Hispanic White male who developed worsening multi-factorial
      encephalopathy in the setting of decompensated alcoholic cirrhosis. He continued
      to deteriorate despite supportive medical therapy, and extensive investigation
      for alternative causes of encephalopathy aside from hepatic was unrevealing; as a
      result, there was concern that his encephalopathy was due to irreversible causes
      from which he may not recover appropriately following LT. We herein: i) describe
      the implementation of MARS as a diagnostic intervention for encephalopathy of
      uncertain etiology in a patient with end stage liver disease who, on the basis of
      prompt psychomotor improvement, underwent LT 19 days post-MARS implementation
      with an excellent clinical outcome and thus ii) propose the use of extracorporeal
      liver support not only as a short-term bridge but also as a diagnostic (and
      potentially therapeutic) measure in cases of cryptogenic encephalopathy,
      particularly in the setting of advanced liver disease.

PMID- 29375651
TI  - Computational FEM Model, Phantom and Ex Vivo Swine Breast Validation of an
      Optimized Double-Slot Microcoaxial Antenna Designed for Minimally Invasive Breast
      Tumor Ablation: Theoretical and Experimental Comparison of Temperature, Size of
      Lesion, and SWR, Preliminary Data.
AB  - Malignant neoplasms are one of the principal world health concerns and breast
      cancer is the most common type of cancer in women. Advances in cancer detection
      technologies allow treating it in early stages; however, it is necessary to
      develop treatments which carry fewer complications and aesthetic repercussions.
      This work presents a feasibility study for the use of microwave ablation as a
      novel technique for breast cancer treatment. A microwave applicator design is
      also being proposed for this purpose. The coupling of the designed antenna was
      predicted with computer simulation. The standing wave ratio obtained through
      simulation was 1.87 and the result of experimental validation was 1.04. The
      optimized antenna has an optimal coupling (SWR = 1.04) so ablation temperatures
      can be achieved in a relatively short time using low power. Varying the time and
      power, the heating pattern can be changed to treat different tumors. However, as
      some discrepancies are still present, a deeper study of the dielectric properties
      and their variation with temperature is required.

PMID- 29375652
TI  - Using Distributed Data over HBase in Big Data Analytics Platform for Clinical
      Services.
AB  - Big data analytics (BDA) is important to reduce healthcare costs. However, there
      are many challenges of data aggregation, maintenance, integration, translation,
      analysis, and security/privacy. The study objective to establish an interactive
      BDA platform with simulated patient data using open-source software technologies
      was achieved by construction of a platform framework with Hadoop Distributed File
      System (HDFS) using HBase (key-value NoSQL database). Distributed data structures
      were generated from benchmarked hospital-specific metadata of nine billion
      patient records. At optimized iteration, HDFS ingestion of HFiles to HBase store
      files revealed sustained availability over hundreds of iterations; however, to
      complete MapReduce to HBase required a week (for 10 TB) and a month for three
      billion (30 TB) indexed patient records, respectively. Found inconsistencies of
      MapReduce limited the capacity to generate and replicate data efficiently. Apache
      Spark and Drill showed high performance with high usability for technical support
      but poor usability for clinical services. Hospital system based on patient
      centric data was challenging in using HBase, whereby not all data profiles were
      fully integrated with the complex patient-to-hospital relationships. However, we
      recommend using HBase to achieve secured patient data while querying entire
      hospital volumes in a simplified clinical event model across clinical services.

PMID- 29375654
TI  - Human papillomavirus genotype distribution in cervical cancer biopsies from
      Nepalese women.
AB  - Background: Cervical cancer (CC) is the leading cause of morbidity and mortality
      from cancer in Nepalese women. Nearly all cases of CC are caused by infection
      with certain genotypes of human papillomavirus (HPV). Data on HPV genotype
      distribution in Nepalese CC patients is sparse. We aimed to determine the
      distribution of HPV genotypes in biopsies of CC tissue from Nepalese women.
      Methods: This study examined 248 archived paraffin-embedded tissue specimens from
      CC cases from patients of B.P. Koirala Memorial Cancer Hospital, Bharatpur,
      Chitwan, Nepal. DNA was extracted from the biopsies and HPV detection performed
      by PCR. HPV genotyping was then carried out by a reverse line hybridization
      technique capable of identifying 36 distinct HPV genotypes. Results: Most of the
      samples were from tumors that had been designated by hospital pathologists as
      squamous cell carcinoma (77.6%). 165 of the 248 samples contained DNA of
      sufficient quality for rigorous PCR testing. All the analyzable specimens were
      positive for HPV. The most common HPV genotypes, in decreasing order of frequency
      were 16, 18, 45, 33, 52, 56 and 31; most were found as single infections (94.5%).
      Together, HPV types 16, 18, and 45 were found in 92% of the tumor samples.
      Conclusion: This study strengthens the knowledge-base of HPV genotype
      distribution in CC cases in Nepal. Hopefully, this information will be useful to
      the medical community and public health policy-makers in generating improved HPV
      surveillance, -prevention and -treatment strategies in Nepal.

PMID- 29375655
TI  - BUILDing SCHOLARS: enhancing diversity among U.S. biomedical researchers in the
      Southwest.
AB  - Background and purpose: With funding from the National Institutes of Health,
      BUILDing SCHOLARS was established at The University of Texas at El Paso with the
      goal of implementing, evaluating and sustaining a suite of institutional, faculty
      and student development interventions in order to train the next generation of
      biomedical researchers from the U.S. Southwest region, where the need is dire
      among underserved communities. The focus is on supporting the infrastructure
      necessary to train and mentor students so they persist on pathways across a range
      of biomedical research fields. The purpose of this article is to highlight the
      design and implementation of BUILDing SCHOLARS' key interventions, which offer a
      systemic student training model for the U.S. Southwest. In-depth reporting of
      evaluation results is reserved for other technical publications. Program and key
      highlights: BUILDing SCHOLARS uses a comprehensive regional approach to
      undergraduate training through a multi-institution consortium that includes 12
      research partners and various pipeline partners across Texas, New Mexico, and
      Arizona. Through faculty collaborations and undergraduate research training, the
      program integrates social and behavioral sciences and biomedical engineering
      while emphasizing seven transdisciplinary nodes of biomedical research excellence
      that are common across partner institutions: addiction, cancer, degenerative and
      chronic diseases, environmental health, health disparities, infectious diseases,
      and translational biomedicine. Key interventions aim to: (1) improve
      institutional capacities by expanding undergraduate research training
      infrastructures; (2) develop an intra- and cross-institutional mentoring-driven
      "community of practice" to support undergraduate student researchers; (3) broaden
      the pool of student participants, improve retention, and increase matriculation
      into competitive graduate programs; and (4) support faculty and postdoctoral
      personnel by training them in research pedagogy and mentoring techniques and
      providing them with resources for increasing their research productivity. Student
      training activities focus on early interventions to maximize retention and on
      enabling students to overcome common barriers by addressing their educational
      endowments, science socialization, network development, family expectations, and
      material resources. Over the long term, BUILDing SCHOLARS will help increase the
      diversity of the biomedical research workforce in the U.S. by meeting the needs
      of students from the Southwest region and by serving as a model for other
      institutions.

PMID- 29375653
TI  - Seeing the unseen of Chinese herbal medicine processing (Paozhi): advances in new
      perspectives.
AB  - Processing (Paozhi) represents a unique Chinese pharmaceutic technique to
      facilitate the use of Chinese herbal medicines (CHMs) for a specific clinical
      need in the guidance of Traditional Chinese Medicine (TCM) theory. Traditionally,
      most CHMs require a proper processing to meet the needs of specific clinical
      syndromes before being prescribed by TCM practitioners. During processing,
      significant changes in chemical profiles occur, which inevitably influence the
      associated pharmacological properties of a CHM. However, although processing is
      formed in a long-term practice, the underlying mechanisms remain unclear for most
      CHMs. The deepening understanding of the mechanism of processing would provide
      scientific basis for standardization of processing. This review introduced the
      role of processing in TCM and several typical methods of processing. We also
      summarized the up-to-date efforts on the mechanistic study of CHM processing. The
      processing mechanisms mainly include the following aspects: (i) directly reducing
      contents of toxic constituents; (ii) structural transformation of constituents;
      (iii) improving solubility of constituents; (iv) physically changing the existing
      form of constituents; (v) and influence by excipients. These progress may give
      new insights into future researches.

PMID- 29375656
TI  - BUILDing BLaST: promoting rural students' biomedical research careers using a
      culturally responsive, one health approach.
AB  - Background and purpose: Most postsecondary institutions in the state of Alaska
      (USA) have a broad mission to serve diverse students, many of whom come from
      schools in rural villages that are accessible only by plane, boat, or snowmobile.
      The major research university, the University of Alaska in Fairbanks (UAF),
      serves a population whereby 40% are from groups recognized as underrepresented in
      the biomedical workforce. The purpose of this article is to describe the Building
      Infrastructure Leading to Diversity (BUILD)-supported program in the state of
      Alaska that seeks to engage students from rural areas with a culturally relevant
      approach that is centered on the One Health paradigm, integrating human, animal,
      and environmental health. Program and key highlights: The Biomedical Learning and
      Student Training (BLaST) program distinguished by broad themes that address
      recruitment, retention, and success of students in biomedical programs,
      especially for students from rural backgrounds. Targeted rural outreach
      emphasizes that biomedical research includes research on the integration of
      human, animal, and environmental health. This One Health perspective gives
      personal relevance and connection to biomedical research. This outreach is
      expected to benefit student recruitment, as well as foster family and community
      support for pursuit of college degrees. BLaST promotes integration of research
      into undergraduate curricula through curriculum development, and by creating a
      new class of instructors, laboratory research and teaching technicians, who
      provide research mentorship, course instruction, and comprehensive advising.
      Finally, BLaST facilitates early and sustained undergraduate research experiences
      in collaborations with graduate students and faculty. Implications: BLaST's
      approach is highly adapted to the Alaskan educational and physical environment,
      but components and concepts could be adapted to other rural areas as a means to
      engage students from rural backgrounds, who often have a closer relationship with
      the natural environment than urban students.

PMID- 29375657
TI  - Using collaborative approaches with a multi-method, multi-site, multi-target
      intervention: evaluating the National Research Mentoring Network.
AB  - Background and purpose: The NIH-funded National Research Mentoring Network (NRMN)
      aims to increase the representation and success of underrepresented groups (URGs)
      in biomedical research by enhancing the training and career development of
      individuals from diverse backgrounds, communities, and cultures. The national
      scope of NRMN, its wide array of innovative programs in mentor and mentee
      matching and training across the career spectrum, requires a collaborative
      evaluation strategy that addresses both internal and external evaluation needs.
      Due to the variety of programs implemented for each target group, the NRMN
      program is responsible for its own process and short-term outcome evaluations and
      the national Coordination and Evaluation Center (CEC) is responsible for
      assessing the medium and long-term effectiveness of the implemented strategies
      and program sustainability. Using a collaborative, utilization-focused evaluation
      framework, both internal NRMN evaluators and the CEC are working to translate
      findings into information that can be used to make both short term and long-term
      decisions about the efficacy and reach of the NRMN model. This important
      information can then inform efforts to institutionalize the current programs and
      potentially replicate them elsewhere. Program and key highlights: The overall
      evaluation of NRMN is guided by both outcome and process questions that are
      tailored for each target group. The different target groups include faculty and
      others who serve as mentors, mentees across academic training and career stages,
      and researchers without a history of independently funded research. NRMN is also
      building the capacity for training those pursuing biomedical careers by
      developing "master trainers" for both mentoring and grantsmanship programs in
      organizations and institutions that can support expanded training efforts aimed
      at diversifying the biomedical workforce. Implications: Results of this
      evaluation will be used to inform the design and implementation of sustainable,
      effective, and comprehensive mentoring and career development initiatives that
      promote diversity in the biomedical research workforce. Our collaborative
      evaluation design, theoretically-derived measurement instruments, efficient data
      systems, and timely reporting serve as an example of how to put evaluation
      principles described into practice for large, multi-site, and multi-dimensional
      research training programs like NRMN.

PMID- 29375658
TI  - A participatory approach to evaluating a national training and institutional
      change initiative: the BUILD longitudinal evaluation.
AB  - Background and purpose: The National Institutes of Health (NIH) funds training
      programs to increase the numbers and skills of scientists who obtain NIH research
      grants, but few programs have been rigorously evaluated. The sizeable recent NIH
      investment in developing programs to increase the diversity of the NIH-funded
      workforce, implemented through the Diversity Program Consortium (DPC), is unusual
      in that it also funds a Consortium-wide evaluation plan, which spans the
      activities of the 10 BUilding Infrastructure Leading to Diversity (BUILD)
      awardees and the National Research Mentoring Network (NRMN). The purpose of this
      article is to describe the evaluation design and innovations of the BUILD Program
      on students, faculty, and institutions of the 10 primarily undergraduate BUILD
      sites. Key highlights of the project: Our approach to this multi-methods quasi
      experimental longitudinal evaluation emphasizes stakeholder participation and
      collaboration. The evaluation plan specifies the major evaluation questions and
      key short- to long-term outcome measures (or Hallmarks of Success). The
      Coordination and Evaluation Center (CEC) embarked on a comprehensive evaluation
      strategy by developing a set of logic models that incorporate the Hallmarks of
      Success and other outcomes that were collaboratively identified by the DPC. Data
      were collected from each BUILD site through national surveys from the Higher
      Education Research Institute at UCLA (HERI), annual followup surveys that align
      with the HERI instruments, site visits and case studies, program encounter data
      ("tracker" data), and institutional data. The analytic approach involves
      comparing changes in Hallmarks (key outcomes) within institutions for biomedical
      students who participated versus those who did not participate in the BUILD
      program at each institution, as well as between institution patterns of
      biomedical students at the BUILD sites, and matched institutions that were not
      BUILD grantees. Case studies provide insights into the institutionalization of
      these new programs and help to explain the processes that lead to the observed
      outcomes. Implications: Ultimately, the results of the consortium-wide evaluation
      will be used to inform national policy in higher education and will provide
      relevant examples of institutional and educational programmatic changes required
      to diversify the biomedical workforce in the USA.

PMID- 29375659
TI  - Enhancing research careers: an example of a US national diversity-focused, grant
      writing training and coaching experiment.
AB  - Background and purpose: Preparing a successful research proposal is one of the
      most complex skills required of professional scientists, yet this skill is rarely
      if ever, taught. A major goal of the National Research Mentoring Network (NRMN)
      in the United States (U.S.) is to support the professional advancement of
      postdoctoral fellows and junior faculty from diverse populations by offering
      intensive coaching in the development of grant proposals early in their careers.
      This article highlights the National Institutes of Health's (NIH) NRMN initiative
      to prepare diverse constituencies of early-stage biomedicine scientists for
      research careers by implementation of an evidence-based nationwide program of
      comprehensive grant writing and professional development. Program and key
      highlights: NRMN delivers four unique but complementary coaching models: the
      Proposal Preparation Program from the University of Minnesota (UMN); Grantwriters
      Coaching Groups from Northwestern University (NU); Grantwriting Uncovered:
      Maximizing Strategies, Help, Opportunities, Experiences from the University of
      Colorado Anschutz Medical Campus (UC) and Washington State University (WSU); and
      Steps Towards Academic Research from the University of North Texas Health Science
      Center (UNTHSC). Because these programs cater to scientists at different career
      stages, rather than employ a single approach, each is uniquely tailored to test
      its efficacy at the national level. The first two models prioritize scientists
      with reasonably well-developed research projects who are ready to write proposals
      for specific NIH research competitions. The other two models target postdoctoral
      fellows and early-career faculty who need more extensive guidance in proposal
      development plans. To achieve scalability, all programs also recruit faculty as
      Coaches-in-Training to learn approaches and acquire particular group facilitation
      skills required by each model. Implications: These efforts exemplify NRMN's
      potential to enhance the career development of diverse trainees on a national
      scale, building research skills, competitiveness for obtaining faculty positions
      and capacities that will result in high quality research proposals from a diverse
      pool of applicants, thereby advancing innovations in science and diversifying the
      U.S. biomedical workforce.

PMID- 29375660
TI  - An entrepreneurial training model to enhance undergraduate training in biomedical
      research.
AB  - Background: Undergraduate students who are interested in biomedical research
      typically work on a faculty member's research project, conduct one distinct task
      (e.g., running gels), and, step by step, enhance their skills. This
      "apprenticeship" model has been helpful in training many distinguished scientists
      over the years, but it has several potential drawbacks. For example, the students
      have limited autonomy, and may not understand the big picture, which may result
      in students giving up on their goals for a research career. Also, the model is
      costly and may greatly depend on a single mentor. Key highlights: The NIH
      Building Infrastructure Leading to Diversity (BUILD) Initiative has been
      established to fund innovative undergraduate research training programs and
      support institutional and faculty development of the recipient university. The
      training model at Morgan State University (MSU), namely "A Student-Centered
      Entrepreneurship Development training model" (ASCEND), is one of the 10 NIH BUILD
      funded programs, and offers a novel, experimental "entrepreneurial" training
      approach. In the ASCEND training model, the students take the lead. They own the
      research, understand the big picture, and experience the entire scope of the
      research process, which we hypothesize will lead to a greater sense of self
      efficacy and research competency, as well as an enhanced sense of science
      identity. They are also immersed in environments with substantial peer support,
      where they can exchange research ideas and share experiences. This is important
      for underrepresented minority students who might have fewer role models and less
      peer support in conducting research. Implications: In this article, we describe
      the MSU ASCEND entrepreneurial training model's components, rationale, and
      history, and how it may enhance undergraduate training in biomedical research
      that may be of benefit to other institutions. We also discuss evaluation methods,
      possible sustainability solutions, and programmatic challenges that can affect
      all types of science training interventions.

PMID- 29375661
TI  - BUILD EXITO: a multi-level intervention to support diversity in health-focused
      research.
AB  - Background and purpose: As part of the NIH BUILD initiative to diversify the
      scientific workforce, the EXITO project is a large multi-institutional effort to
      provide comprehensive support and training for undergraduates from traditionally
      underrepresented student populations who aspire to health-related research
      careers. Portland State University, a major public urban university that
      prioritizes student access and opportunity, and Oregon Health & Science
      University, a research-intensive academic health center, lead the EXITO network
      comprised of eleven 2-year and 4-year institutions of higher education spanning
      Oregon, Washington, Alaska, Hawaii, Guam, American Samoa, and the Northern
      Mariana Islands. The EXITO project aims for impact in biomedical research by
      training diverse scholars from indigenous and underserved communities affected by
      adverse health disparities. Project approach: Guided by socio-ecological theory,
      the EXITO project is a multi-level intervention offering a three-year research
      training pathway for scholars in the biomedical, behavioral, health, and social
      sciences. Fundamental components of the model include student outreach and
      engagement, integrated curricular enhancements, intensive research experiences,
      multi-faceted developmental mentoring, supportive community and services, and
      rigorous evaluation and quality improvement. EXITO also advances faculty and
      institutional development in these domains by holding curriculum development
      conferences, creating research learning communities, awarding pilot project
      research funding, providing mentor training and ongoing support, collaborating
      with other research equity programs, and developing campus infrastructure and
      services to support scholars with diverse backgrounds and needs. Highlights: The
      large and geographically broad network of EXITO institutions engages a range of
      diverse students, including indigenous populations and students beginning post
      secondary education at community colleges. The EXITO model specifically
      accommodates many students transferring from 2-year partner institutions and
      facilitates seamless transfer to the 4-year institution. EXITO features several
      approaches to research training, including supported summer entry into research
      placements, the incorporation of responsible conduct of research content into
      general education curriculum, and the intentional matching of scholars with three
      types of mentors (e.g., peer, career, research). Implications: EXITO provides an
      example of a comprehensive research training initiative for traditionally
      underrepresented students that can be implemented across a diverse range of 2
      year and 4-year institutions.

PMID- 29375662
TI  - Critical race theory as a bridge in science training: the California State
      University, Northridge BUILD PODER program.
AB  - Background and purpose: Unconscious bias and explicit forms of discrimination
      continue to pervade academic institutions. Multicultural and diversity training
      activities have not been sufficient in making structural and social changes
      leading to equity, therefore, a new form of critical consciousness is needed to
      train diverse scientists with new research questions, methods, and perspectives.
      The purpose of this paper is to describe Building Infrastructure Leading to
      Diversity (BUILD); Promoting Opportunities for Diversity in Education and
      Research (PODER), which is an undergraduate biomedical research training program
      based on transformative framework rooted in Critical Race Theory (CRT). Key
      highlights: By employing a CRT-informed curriculum and training in BUILD PODER,
      students are empowered not only to gain access but also to thrive in graduate
      programs and beyond. Poder means "power" or "to be able to" in Spanish.
      Essentially, we are "building power" using students' strengths and empowering
      them as learners. The new curriculum helps students understand institutional
      policies and practices that may prevent them from persisting in higher education,
      learn to become their own advocates, and successfully confront social barriers
      and instances of inequities and discrimination. To challenge these barriers and
      sustain campus changes in support of students, BUILD PODER works toward changing
      campus culture and research mentoring relationships. By joining with ongoing
      university structures such as the state university Graduation Initiative, we
      include CRT tenets into the campus dialogue and stimulate campus-wide discussions
      around institutional change. Strong ties with five community college partners
      also enrich BUILD PODER's student body and strengthen mentor diversity.
      Preliminary evaluation data suggest that BUILD PODER's program has enhanced the
      racial/ethnic consciousness of the campus community, is effective in encouraging
      more egalitarian and respectful faculty-student relationships, and is a rigorous
      program of biomedical research training that supports students as they achieve
      their goals. Implications: Biomedical research programs may benefit from a
      reanalysis of the fit between current training programs and student strengths. By
      incorporating the voices of talented youth, drawing upon their native strengths,
      we will generate a new science that links biomedical research to community health
      and social justice, generating progress toward health equity through a promising
      new generation of scholars.

PMID- 29375664
TI  - A research-based inter-institutional collaboration to diversify the biomedical
      workforce: ReBUILDetroit.
AB  - Background and purpose: Faced with decades of severe economic decline, the city
      of Detroit, Michigan (USA) is on the cusp or reinventing itself. A Consortium was
      formed of three higher education institutions that have an established mission to
      serve an urban population and a vested interest in the revitalization of the
      health, welfare, and economic opportunity in the Detroit metro region that is
      synergistic with national goals to diversify the biomedical workforce. The
      purpose of this article is to describe the rationale, approach, and model of the
      Research Enhancement for BUILDing Detroit (ReBUILDetroit) Consortium, as a cross
      campus collaborative for students, faculty, and institutional development. The
      ReBUILDetroit program is designed to transform the culture of higher education in
      Detroit, Michigan by educating and training students from diverse and socio
      economically disadvantaged backgrounds to become the next generation of
      biomedical researchers. Key program highlights: Marygrove College, University of
      Detroit Mercy, and Wayne State University established a Consortium to create and
      implement innovative, evidence-based and cutting-edge programming. Specific
      elements include: (1) a pre-college summer enrichment experience; (2) an inter
      institutional curricular re-design of target foundational courses in biology,
      chemistry and social science using the Research Coordination Network (RCN) model;
      and (3) cross-institutional summer faculty-mentored research projects for
      ReBUILDetroit Scholars starting as rising sophomores. Student success support
      includes intentional and intrusive mentoring, financial support, close faculty
      engagement, ongoing workshops to overcome academic and non-academic barriers, and
      cohort building activities across the Consortium. Institutional supports,
      integral to program creation and sustainability, include creating faculty
      learning communities grounded in professional development opportunities in
      pedagogy, research and mentorship, and developing novel partnerships and
      accelerated pipeline programming across the Consortium. This article highlights
      the development, implementation and evolution of high-impact practices critical
      for student learning, research-based course development, and the creation of
      inter-institutional learning communities as a direct result of ReBUILDetroit.
      Implications: Our cross-institutional collaboration and leveraging of resources
      in a difficult economic environment, drawing students from high schools with a
      myriad of strengths and challenges, serves as a model for higher education
      institutions in large, urban centers who are seeking to diversify their
      workforces and provide additional opportunities for upward mobility among diverse
      populations.

PMID- 29375665
TI  - Think 500, not 50! A scalable approach to student success in STEM.
AB  - Background: UMBC, a diverse public research university, "builds" upon its
      reputation in producing highly capable undergraduate scholars to create a
      comprehensive new model, STEM BUILD at UMBC. This program is designed to help
      more students develop the skills, experience and motivation to excel in science,
      technology, engineering, and mathematics (STEM). This article provides an in
      depth description of STEM BUILD at UMBC and provides the context of this
      initiative within UMBC's vision and mission. Key highlights: The STEM BUILD model
      targets promising STEM students who enter as freshmen or transfer students and do
      not qualify for significant university or other scholarship support. Of primary
      importance to this initiative are capacity, scalability, and institutional
      sustainability, as we distill the advantages and opportunities of UMBC's
      successful scholars programs and expand their application to more students. The
      general approach is to infuse the mentoring and training process into the fabric
      of the undergraduate experience while fostering community, scientific identity,
      and resilience. At the heart of STEM BUILD at UMBC is the development of BUILD
      Group Research (BGR), a sequence of experiences designed to overcome the
      challenges that undergraduates without programmatic support often encounter
      (e.g., limited internship opportunities, mentorships, and research positions for
      which top STEM students are favored). BUILD Training Program (BTP) Trainees serve
      as pioneers in this initiative, which is potentially a national model for
      universities as they address the call to retain and graduate more students in
      STEM disciplines - especially those from underrepresented groups. As such, BTP is
      a research study using random assignment trial methodology that focuses on the
      scalability and eventual incorporation of successful measures into the
      traditional format of the academy. Implications: Critical measures to transform
      institutional culture include establishing an extensive STEM Living and Learning
      Community to increase undergraduate retention, expanding the adoption of "active
      learning" pedagogies to increase the efficiency of learning, and developing
      programs to train researchers to effectively mentor a greater portion of the
      student population. The overarching goal of STEM BUILD at UMBC is to retain
      students in STEM majors and better prepare them for post baccalaureate, graduate,
      or professional programs as well as careers in biomedical and behavioral
      research.

PMID- 29375666
TI  - Enabling full representation in science: the San Francisco BUILD project's agents
      of change affirm science skills, belonging and community.
AB  - Background: The underrepresentation of minority students in the sciences
      constrains innovation and productivity in the U.S. The SF BUILD project mission
      is to remove barriers to diversity by taking a "fix the institution" approach
      rather than a "fix the student" one. SF BUILD is transforming education,
      research, training, and mentoring at San Francisco State University, a premiere
      public university that primarily serves undergraduates and ethnic minority
      students. It boasts a large number of faculty members from underrepresented
      groups (URGs), including many of the project leaders. These leaders collaborate
      with faculty at the University of California San Francisco (UCSF), a world-class
      medical research institution, to implement SF BUILD. Key highlights: Together,
      the campus partners are committed to creating intellectually safe and affirming
      environments grounded in the Signaling Affirmation for Equity (SAFE) model, which
      is based on robust psychosocial evidence on stereotype threat and its
      consequences. The SAFE model dictates a multilevel approach to increasing intent
      to pursue a biomedical career, persistence in STEM fields, and productivity (e.g.
      publications, presentations, and grants) by implementing transformative
      activities at the institutional, faculty, and student levels. These activities
      (1) increase knowledge of the stereotype threat phenomenon; (2) affirm communal
      and altruistic goals of students and faculty to "give back" to their communities
      in classrooms and research activities; and (3) establish communities of students,
      faculty and administrators as "agents of change." Agents of change are persons
      committed to establishing and maintaining SAFE environments. In this way, SF
      BUILD advances the national capacity to address biomedical questions relevant to
      communities of color by enabling full representation in science. Implications:
      This chapter describes the theoretical and historical context that drive the
      activities, research and evaluation of the SF BUILD project, and highlights
      attributes that other institutions can use for institutional change. While this
      paper is grounded in psychosocial theory, it also provides practical solutions
      for broadening participation.

PMID- 29375667
TI  - Advancing research opportunities and promoting pathways in graduate education: a
      systemic approach to BUILD training at California State University, Long Beach
      (CSULB).
AB  - Background and purpose: First-generation college graduates, racial and ethnic
      minorities, people with disabilities, and those from disadvantaged backgrounds
      are gravely underrepresented in the health research workforce representing
      behavioral health sciences and biomedical sciences and engineering (BHS/BSE).
      Furthermore, relative to their peers, very few students from these
      underrepresented groups (URGs) earn scientific bachelor's degrees with even fewer
      earning doctorate degrees. Therefore, programs that engage and retain URGs in
      health-related research careers early on in their career path are imperative to
      promote the diversity of well-trained research scientists who have the ability to
      address the nation's complex health challenges in an interdisciplinary way. The
      purpose of this paper is to describe the challenges, lessons learned, and
      sustainability of implementing a large-scale, multidisciplinary research
      infrastructure at California State University, Long Beach (CSULB) - a minority
      serving institution - through federal funding received by the National Institutes
      of Health (NIH) Building Infrastructure Leading to Diversity (BUILD) Initiative.
      Program and key highlights: The CSULB BUILD initiative consists of developing a
      research infrastructure designed to engage and retain URGs on the research career
      path by providing them with the research training and skills needed to make them
      highly competitive for doctoral programs and entry into the research workforce.
      This initiative unites many research disciplines using basic, applied, and
      translational approaches to offer insights and develop technologies addressing
      prominent community and national health issues from a multidisciplinary
      perspective. Additionally, this initiative brings together local (e.g., high
      school, community college, doctoral research institutions) and national (e.g.,
      National Research Mentoring Network) collaborative partners to alter how we
      identify, develop, and implement resources to enhance student and faculty
      research. Finally, this initiative establishes a student research training
      program that engages URGs earlier in their academic development, is larger and
      multidisciplinary in scope, and is responsive to the life contexts and promotes
      the cultural capital that URGs bring to their career path. Implications: Although
      there have been many challenges to planning for and developing CSULB BUILD's
      large-scale, multidisciplinary research infrastructure, there have been many
      lessons learned in the process that could aid other campuses in the development
      and sustainability of similar research programs.

PMID- 29375668
TI  - Evaluating efforts to diversify the biomedical workforce: the role and function
      of the Coordination and Evaluation Center of the Diversity Program Consortium.
AB  - Background: The National Institutes of Health (NIH)-funded Diversity Program
      Consortium (DPC) includes a Coordination and Evaluation Center (CEC) to conduct a
      longitudinal evaluation of the two signature, national NIH initiatives - the
      Building Infrastructure Leading to Diversity (BUILD) and the National Research
      Mentoring Network (NRMN) programs - designed to promote diversity in the NIH
      funded biomedical, behavioral, clinical, and social sciences research workforce.
      Evaluation is central to understanding the impact of the consortium activities.
      This article reviews the role and function of the CEC and the collaborative
      processes and achievements critical to establishing empirical evidence regarding
      the efficacy of federally-funded, quasi-experimental interventions across
      multiple sites. The integrated DPC evaluation is particularly significant because
      it is a collaboratively developed Consortium Wide Evaluation Plan and the first
      hypothesis-driven, large-scale systemic national longitudinal evaluation of
      training programs in the history of NIH/National Institute of General Medical
      Sciences. Key highlights: To guide the longitudinal evaluation, the CEC-led
      literature review defined key indicators at critical training and career
      transition points - or Hallmarks of Success. The multidimensional, comprehensive
      evaluation of the impact of the DPC framed by these Hallmarks is described. This
      evaluation uses both established and newly developed common measures across
      sites, and rigorous quasi-experimental designs within novel multi-methods
      (qualitative and quantitative). The CEC also promotes shared learning among
      Consortium partners through working groups and provides technical assistance to
      support high-quality process and outcome evaluation internally of each program.
      Finally, the CEC is responsible for developing high-impact dissemination channels
      for best practices to inform peer institutions, NIH, and other key national and
      international stakeholders. Implications: A strong longitudinal evaluation across
      programs allows the summative assessment of outcomes, an understanding of factors
      common to interventions that do and do not lead to success, and elucidates the
      processes developed for data collection and management. This will provide a
      framework for the assessment of other training programs and have national
      implications in transforming biomedical research training.

PMID- 29375669
TI  - Building integrated pathways to independence for diverse biomedical researchers:
      Project Pathways, the BUILD program at Xavier University of Louisiana.
AB  - Background and purpose: Xavier University of Louisiana is a historically Black
      and Catholic university that is nationally recognized for its science,
      technology, engineering and mathematics (STEM) curricula. Approximately 73% of
      Xavier's students are African American, and about 77% major in the biomedical
      sciences. Xavier is a national leader in the number of STEM majors who go on to
      receive M.D. degrees and Ph.D. degrees in science and engineering. Despite
      Xavier's advances in this area, African Americans still earn about 7.5% of the
      Bachelor's degrees, less than 8% of the Master's degrees, and less than 5% of the
      doctoral degrees conferred in STEM disciplines in the United States.
      Additionally, although many well-prepared, highly-motivated students are
      attracted by Xavier's reputation in the sciences, many of these students, though
      bright and capable, come from underperforming public school systems and receive
      substandard preparation in STEM disciplines. The purpose of this article is to
      describe how Xavier works to overcome unequal education backgrounds and
      socioeconomic challenges to develop student talent through expanding biomedical
      training opportunities and build on an established reputation in science
      education. Program and key highlights: The National Institutes of Health
      (NIH)/National Institute of General Medical Sciences (NIGMS)-funded BUILD
      (Building Infrastructure Leading to Diversity) Program at Xavier University of
      Louisiana, Project Pathways, is a highly-innovative program designed to broaden
      the career interests of students early on, and to engage them in activities that
      entice them to continue their education towards biomedical research careers.
      Project strategies involve a transformation of Xavier's academic and non-academic
      programs through the redesign, supplementation and integration of academic
      advising, tutoring, career services, personal counseling, undergraduate research
      training, faculty research mentoring, and development of new biomedical and
      research skills courses. The Program also focuses on mentor training and
      providing faculty members with opportunities to improve their teaching skills as
      well as their research competitiveness. In addition to the wide range of
      activities supported by BUILD within the institution, Xavier University is
      partnering with a number of major research universities across the nation to
      achieve Project Pathways' goals. Implications: The strategies developed by
      Project Pathways are designed to address the challenges and barriers Xavier
      students face as they work towards graduate studies and entering the biomedical
      workforce. Xavier University of Louisiana has a long history of providing high
      quality, rigorous education to African American students in a very supportive
      environment with highly dedicated faculty and staff. The program highlighted here
      could be used by other institutions as a model program for assisting students in
      STEM and other biomedical fields of study to successfully matriculate through
      college and graduate school and develop their research careers.

PMID- 29375663
TI  - A new approach to mentoring for research careers: the National Research Mentoring
      Network.
AB  - Background and purpose: Effective mentorship is critical to the success of early
      stage investigators, and has been linked to enhanced mentee productivity, self
      efficacy, and career satisfaction. The mission of the National Research Mentoring
      Network (NRMN) is to provide all trainees across the biomedical, behavioral,
      clinical, and social sciences with evidence-based mentorship and professional
      development programming that emphasizes the benefits and challenges of diversity,
      inclusivity, and culture within mentoring relationships, and more broadly the
      research workforce. The purpose of this paper is to describe the structure and
      activities of NRMN. Key highlights: NRMN serves as a national training hub for
      mentors and mentees striving to improve their relationships by better aligning
      expectations, promoting professional development, maintaining effective
      communication, addressing equity and inclusion, assessing understanding,
      fostering independence, and cultivating ethical behavior. Training is offered in
      person at institutions, regional training, or national meetings, as well as via
      synchronous and asynchronous platforms; the growing training demand is being met
      by a cadre of NRMN Master Facilitators. NRMN offers career stage-focused coaching
      models for grant writing, and other professional development programs. NRMN
      partners with diverse stakeholders from the NIH-sponsored Diversity Program
      Consortium (DPC), as well as organizations outside the DPC to work
      synergistically towards common diversity goals. NRMN offers a virtual portal to
      the Network and all NRMN program offerings for mentees and mentors across career
      development stages. NRMNet provides access to a wide array of mentoring
      experiences and resources including MyNRMN, Guided Virtual Mentorship Program,
      news, training calendar, videos, and workshops. National scale and sustainability
      are being addressed by NRMN "Coaches-in-Training" offerings for more senior
      researchers to implement coaching models across the nation. "Shark Tanks" provide
      intensive review and coaching for early career health disparities investigators,
      focusing on grant writing for graduate students, postdoctoral trainees, and
      junior faculty. Implications: Partners from diverse perspectives are building the
      national capacity and sparking the institutional changes necessary to truly
      diversify and transform the biomedical research workforce. NRMN works to leverage
      resources towards the goals of sustainability, scalability, and expanded reach.

PMID- 29375670
TI  - Chromothripsis 18 in multiple myeloma patient with rapid extramedullary relapse.
AB  - Background: Catastrophic chromosomal event known as chromothripsis was proven to
      be a significant hallmark of poor prognosis in several cancer diseases. While
      this phenomenon is very rare in among multiple myeloma (MM) patients, its
      presence in karyotype is associated with very poor prognosis. Case presentation:
      In our case, we report a 62 year female patient with rapid progression of
      multiple myeloma (MM) into extramedullary disease and short overall survival (OS
      = 23 months). I-FISH investigation revealed presence of gain 1q21 and
      hyperdiploidy (+ 5,+ 9,+ 15) in 82% and 86%, respectively, while IgH
      rearrangements, del(17)(p13) and del(13)(q14) were evaluated as negative.Whole
      genome profiling using array-CGH showed complex genomic changes including
      hyperdiploidy (+ 3,+ 5,+ 9,+ 11, + 15,+ 19), monosomy X, structural gains (1q21
      1q23.1, 1q32-1q44, 16p13.13-16p11.2) and losses (1q23.1-1q32.1; 8p23.3-8p11.21)
      of genetic material and chromothripsis in chromosome 18 with 6 breakpoint areas.
      Next-generation sequencing showed a total of 338 variants with 1.8% (6/338) of
      pathological mutations in NRAS (c.181C > A; p.Gln61Lys) or variants of unknown
      significance in TP53, CUX1 and POU4F1. Conclusions: Our findings suggest that
      presence of chromothripsis should be considered as another important genetic
      hallmark of poor prognosis in MM patients and utilization of genome-wide
      screening techniques such as array-CGH and NGS improves the clinical diagnostics
      of the disease.

PMID- 29375672
TI  - Complete genome sequence of Lactobacillus pentosus SLC13, isolated from mustard
      pickles, a potential probiotic strain with antimicrobial activity against
      foodborne pathogenic microorganisms.
AB  - Background: Lactobacillus pentosus SLC13 is a high exopolysaccharide (EPS)
      producing strain with broad-spectrum antimicrobial activity and the ability to
      grow in simulated gastrointestinal conditions. SLC13 was isolated from mustard
      pickles in Taiwan for potential probiotic applications. To better understand the
      molecular base for its antimicrobial activity and high EPS production, entire
      genome of SLC13 was determined by PacBio SMRT sequencing. Results: L. pentosus
      SLC13 contains a genome with a 3,520,510-bp chromosome and a 62,498-bp plasmid.
      GC content of the complete genome was 46.5% and that of plasmid pSLC13 was 41.3%.
      Sequences were annotated at the RAST prokaryotic genome annotation server, and
      the results showed that the genome contained 3172 coding sequences and 82 RNA
      genes. Seventy-six protein-coding sequences were identified on the plasmid
      pSLC13. A plantaricin gene cluster, which is responsible for bacteriosins
      biosynthesis and could be associated with its broad-spectrum antimicrobial
      activity, was identified based on comparative genomic analysis. Two gene clusters
      involved in EPS production were also identified. Conclusion: This genomic
      sequence might contribute to a future application of this strain as probiotic in
      productive livestock potentially inhibiting competing and pathogenic organisms.

PMID- 29375671
TI  - Management of hypothyroidism with combination thyroxine (T4) and triiodothyronine
      (T3) hormone replacement in clinical practice: a review of suggested guidance.
AB  - Background: Whilst trials of combination levothyroxine/liothyronine therapy
      versus levothyroxine monotherapy for thyroid hormone replacement have not shown
      any superiority, there remains a small subset of patients who do not feel well on
      monotherapy. Whilst current guidelines do not suggest routine use of combination
      therapy they do acknowledge a trial in such patients may be appropriate. It
      appears that use of combination therapy and dessicated thyroid extract is not
      uncommon but often being used by non-specialists and not adequately monitored.
      This review aims to provide practical advice on selecting patients, determining
      dose and monitoring of such a trial. Main body: It is important to select the
      correct patient for a trial so as to not delay diagnosis or potentially worsen an
      undiagnosed condition. An appropriate starting dose may be calculated but
      accuracy is limited by available formulations and cost. Monitoring of thyroid
      function, benefits and adverse effects are vital in the trial setting given lack
      of evidence of safe long term use. Also important is that patients understand set
      up of the trial, potential risks involved and give consent. Conclusion: Whilst
      evidence is lacking on whether a small group of patients may benefit from
      combination therapy a trial may be indicated in those who remain symptomatic
      despite adequate levothyroxine monotherapy. This should be undertaken by
      clinicians experienced in the field with appropriate monitoring for adverse
      outcomes in both short and long term.

PMID- 29375673
TI  - Reduced feeding activity of soil detritivores under warmer and drier conditions.
AB  - Anthropogenic warming is projected to trigger positive feedbacks to climate by
      enhancing carbon losses from the soil1. While such losses are, in part, owing to
      increased decomposition of organic matter by invertebrate detritivores, it is
      unknown how detritivore feeding activity will change with warming2, especially
      under drought conditions. Here, using four year manipulation experiments in two
      North American boreal forests, we investigate how temperature (ambient, +1.7 
      degrees C, +3.4  degrees C) and rainfall (ambient, -40% summer precipitation)
      perturbations influence detritivore feeding activity. In contrast to general
      expectations1,3, warming had negligible net effects on detritivore feeding
      activity at ambient precipitation. However, when combined with precipitation
      reductions, warming decreased feeding activity by ~14%. As across all plots and
      dates, detritivore feeding activity was positively associated to bulk soil
      microbial respiration, our results suggest slower rates of decomposition of soil
      organic matter, and thus reduced positive feedbacks to climate under
      anthropogenic climate change.

PMID- 29375674
TI  - Recent perspectives of pediatric mitochondrial diseases.
AB  - Mitochondrial disorders are amongst the most common groups of inborn errors of
      metabolism. They are caused by deficiencies in the final pathway of the cellular
      energy production, the mitochondrial respiratory chain. The disorders are
      clinically and genetically heterogeneous and the aetiology could be found in the
      mitochondrial, or in the nuclear genome. We searched important e-databases for
      the collection of latest literature on the mitochondrial disease especially in
      pediatric population. Most of the studies in the recent past have focused on the
      understanding of the clinical phenotypes and pathophysiological mechanisms. Leigh
      syndrome is a common severe, neurodegenerative disease of early childhood. A
      defect in the POLG gene is another common observation in most of the cases
      leading to Alpers syndrome. The review concludes that pediatric mitochondrial
      disorders are severe, progressive and usually multi-systemic. Further, whole
      genome sequencing is an excellent diagnostic option.

PMID- 29375675
TI  - Puerarin promotes the proliferation and differentiation of MC3T3-E1 cells via
      microRNA-106b by targeting receptor activator of nuclear factor-kappaB ligand.
AB  - Puerarin, an isoflavone-C-glucoside extracted from the root of Pueraria Labata
      (Willd.) Ohwi, is one of the most important crude herbs used in Chinese medicine
      for various medicinal purposes. Accumulating evidence has indicated that puerarin
      suppresses bone resorption and promotes bone formation. However, the molecular
      mechanism involved in puerarin-associated bone formation is unclear. The present
      study aimed to investigate the molecular mechanism of puerarin-induced osteoblast
      proliferation and differentiation. The study showed that puerarin treatment
      differentially affected cell proliferation in a time-dependent manner. Notably,
      at a concentration of 20 uM, puerarin significantly promoted cell proliferation
      in comparison with the control (P<0.01). Furthermore, puerarin promoted MC3T3-E1
      cell differentiation at an appropriate concentration. In addition, miR-106b was
      significantly upregulated in MC3T3-E1 cells following treatment with 20 uM
      puerarin (P<0.01), and a known target for miR-106b, receptor activator of nuclear
      factor-kappaB ligand (RANKL) was demonstrated using the luciferase reporter
      assay. Furthermore, inhibition of miR-106b significantly reversed the promotion
      of cell differentiation induced by puerarin in MC3T3-E1 cells (P<0.01). In
      conclusion, the present study demonstrated that puerarin exerts its role in MC3T3
      E1 osteogenesis through miR-106b by targeting RANKL. The findings suggest that
      puerarin may be considered a promising anti-osteoporotic agent for the treatment
      of osteoporosis.

PMID- 29375676
TI  - Fibroblast growth factor 21 inhibition aggravates cardiac dysfunction in diabetic
      cardiomyopathy by improving lipid accumulation.
AB  - Diabetic cardiomyopathy (DCM) is one of the major causes of morbidity and
      mortality in diabetic patients. Recent studies have demonstrated an increased
      level of fibroblast growth factor 21 (FGF21) in the plasma of DCM patients, and
      FGF21 has been proven to be a cardiovascular protector of the heart. The present
      study aimed to further investigate the pathogenic role of FGF21 in DCM,
      hypothesizing that a lack of FGF21 may promote the progression of DCM by
      regulating the lipid metabolism, cardiac hypertrophy and cardiac fibrosis, thus
      deteriorating the cardiac dysfunction. A total of 44 mice were randomly assigned
      into the normal (n=6), DCM (n=6), normal + scrambled siRNA (n=6), DCM + scrambled
      siRNA (n=6), normal + FGF21 siRNA (n=10) and DCM + FGF21 siRNA (n=10) groups.
      Type 1 diabetes mellitus was induced to mice in the DCM groups by streptozotocin
      injection, while FGF21 expression was inhibited by FGF21 siRNA. Normal and DCM
      mice administrated with scrambled siRNA were respectively regarded as the
      controls for the normal + FGF21 siRNA and DCM + FGF21 siRNA groups. In the DCM
      group, FGF21 inhibition promoted cardiac hypertrophy and fibrosis, and the
      expression levels of their indicators, including atrial natriuretic factor, alpha
      skeletal actin, collagen type I and III, and transforming growth factor-beta,
      increased, leading to further decreased cardiac function. In addition, FGF21
      inhibition in DCM mice elevated the quantity of lipid droplets and the
      concentration of heart triglycerides, plasma triglycerides and cholesterol
      levels, accompanied by downregulation of peroxisome proliferator-activated
      receptor gamma co-activator 1alpha (PGC-1alpha) and upregulation of cluster of
      differentiation (CD)36. Thus, the results indicated that FGF21 inhibition
      exacerbates the cardiac dysfunction by aggravating the lipid accumulation through
      regulating the expression levels of PGC-1alpha and CD36. In conclusion, it is
      suggested that FGF21 may be a potentially useful agent in the treatment of DCM.

PMID- 29375677
TI  - Quantifying the degradation of degradable implants and bone formation in the
      femoral condyle using micro-CT 3D reconstruction.
AB  - Degradation limits the application of magnesium alloys, and evaluation methods
      for non-traumatic in vivo quantification of implant degradation and bone
      formation are imperfect. In the present study, a micro-arc-oxidized AZ31
      magnesium alloy was used to evaluate the degradation of implants and new bone
      formation in 60 male New Zealand white rabbits. Degradation was monitored by
      weighing the implants prior to and following implantation, and by performing
      micro-computed tomography (CT) scans and histological analysis after 1, 4, 12,
      24, 36, and 48 weeks of implantation. The results indicated that the implants
      underwent slow degradation in the first 4 weeks, with negligible degradation in
      the first week, followed by significantly increased degradation during weeks 12
      24 (P<0.05), and continued degradation until the end of the 48-week experimental
      period. The magnesium content decreased as the implant degraded (P<0.05);
      however, the density of the material exhibited almost no change. Micro-CT results
      also demonstrated that pin volume, pin mineral density, mean 'pin thickness',
      bone surface/bone volume and trabecular separation decreased over time (P<0.05),
      and that the pin surface area/pin volume, bone volume fraction, trabecular
      thickness, trabecular number and tissue mineral density increased over time
      (P<0.05), indicating that the number of bones and density of new bone increased
      as magnesium degraded. These results support the positive effect of magnesium on
      osteogenesis. However, from the maximum inner diameter of the new bone loop and
      diameter of the pin in the same position, the magnesium alloy was not capable of
      creating sufficient bridges between the bones and biomaterials when there were
      preexisting gaps. Histological analyses indicated that there were no inflammatory
      responses around the implants. The results of the present study indicate that a
      micro-arc-oxidized AZ31 magnesium alloy is safe in vivo and efficiently degraded.
      Furthermore, the novel bone formation increased as the implant degraded. The
      findings concluded that micro-CT, which is useful for providing non-traumatic, in
      vivo, quantitative and precise data, has great value for exploring the
      degradation of implants and novel bone formation.

PMID- 29375678
TI  - Aberrant DNA methylation associated with Alzheimer's disease in the superior
      temporal gyrus.
AB  - Abnormal DNA methylation patterns have been demonstrated to be associated with
      the pathogenesis of Alzheimer's disease (AD). The present study aimed to identify
      differential methylation in the superior temporal gyrus (STG) of patients with
      late-onset AD based on epigenome-wide DNA methylation data by bioinformatics
      analysis. The genome-wide DNA methylation data in the STG region of 34 patients
      with late-onset AD and 34 controls without dementia were recruited from the Gene
      Expression Omnibus database. Through systemic quality control, differentially
      methylated CpG sites were determined by the Student's t-test and mean methylation
      value differences between the two conditions. Hierarchical clustering analysis
      was applied to assess the classification performance of differentially methylated
      CpGs. Functional analysis was performed to investigate the biological functions
      of the genes associated with differentially methylated CpGs. A total of 17,895
      differentially methylated CpG sites were initially identified, including 11,822
      hypermethylated CpGs and 6,073 hypomethylated CpGs. Further analysis examined
      2,211 differentially methylated CpGs (covering 1,991 genes). AD subjects
      demonstrated distinctive DNA methylation patterns when compared with the
      controls, with a classification accuracy value of 1. Hypermethylation was mainly
      detected for genes regulating the cell cycle progression, whereas hypomethylation
      was observed in genes involved in transcription factor binding. The present study
      demonstrated widespread and distinctive DNA methylation alterations in late-onset
      AD. Identification of AD-associated epigenetic biomarkers may allow for the
      development of novel diagnostic and therapeutic targets.

PMID- 29375679
TI  - The efficacy of homemade tolcapone in the treatment of patients with Parkinsons
      disease.
AB  - The aim of the study was to investigate the efficacy of homemade tolcapone in
      treatment of patients with Parkinson's disease (PD). Eighty patients with PD were
      subjected to randomized, double-blind, placebo-controlled and parallel-group
      study. PD patients were randomly divided into the tolcapone treatment group (41
      cases) and placebo group (39 cases). Each patient received 1 pill of tolcapone or
      placebo, 3 times per day for 26 weeks. Efficacy was evaluated using the
      internationally used unified Parkinson's disease rating scale (UPDRS) scoring
      system for PD symptoms. After the treatment for 26 weeks, the cognitive function,
      tremor, muscle stiffness, voluntary movement and autonomic nerve symptoms were
      compared between the two groups using UPDRS scores. Compared with the placebo
      group, cognitive function, muscle stiffness and voluntary movement reduction were
      significantly improved in patients of the tolcapone group (P<0.05). However, no
      significant differences in UPDRS scores of autonomic nerve symptoms and tremor
      were found between two groups after treatment (P>0.05). Tolcapone, a catechol-O
      methyl transferase (COMT) inhibitor, can improve the motor function of patients
      with PD, especially exercise and muscle stiffness. Tolcapone can also improve the
      cognitive function of patients.

PMID- 29375680
TI  - Mitochondrial factor and cell cytokines associate with TCM syndrome scale in
      vascular dementia patients.
AB  - Mitochondrial factor and cell cytokines play important roles in the incidence of
      vascular dementia (VD), but their correlations with inflammatory and
      mitochondrial factors and the role of both in the kidney essence deficiency
      pattern and phlegm turbidity blocking orifice pattern are not clear. This study
      was aimed at studying the correlations between the serum mitochondrial factor and
      cell cytokines with TCM Syndrome Scale in vascular dementia. According to the
      inclusion criteria we collected 108 vascular dementia patients which were divided
      into the kidney essence deficiency pattern and phlegm turbidity blocking orifice
      pattern based on the TCM Syndrome Scale. We measured serum tumor necrosis factor
      alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-18 (IL-18) concentration
      using an enzyme-linked immunosorbent assay (ELISA) and serum malondialdelyde
      (MDA) and superoxide dismutase (SOD) was quantified according to instructions of
      kits from the 108 patients (45 in kidney essence deficiency pattern, 63 in phlegm
      turbidity blocking orifice pattern). The scale scores were assessed using TCM
      Syndrome Scale, MMSE, Hachinski, Barthel, BBS, CDR. There was a significant
      difference on the scores of CDR and the factors of the memory, judgment, social
      affairs, personal care, family and hobbies among the two groups, The means of
      kidney essence deficiency group was higher than that of phlegm turbidity blocking
      orifice pattern group. IL-18 and SOD in the phlegm turbidity blocking orifice
      group was higher than those in the kidney essence deficiency pattern; IL-6 in
      phlegm turbidity blocking orifice pattern group was lower than that in the kidney
      essence deficiency pattern. By logistic regression analysis, we demonstrated that
      high concentration of IL-6, TNF-alpha, and MDA were associated with increased TCM
      syndrome scores in two groups, while IL-6, IL-18, TNF-alpha, SOD were associated
      with decreased MMSE, Barthel. Our study support the notion that IL-6 plays a more
      important role in the integral of kidney essence deficiency pattern, IL-18 is a
      more important factor in phlegm turbidity blocking orifice pattern. The results
      can be used as the theoretical basis of traditional Chinese Medicine prescription
      and pharmacological research in future, through decrease in IL-6 lever and
      increase in SOD in integral kidney essence deficiency pattern, and IL-18 as the
      main anti inflammation index in phlegm turbidity blocking orifice pattern.

PMID- 29375681
TI  - Alendronate promotes osteoblast differentiation and bone formation in ovariectomy
      induced osteoporosis through interferon-beta/signal transducer and activator of
      transcription 1 pathway.
AB  - Alendronate is commonly used for the treatment of postmenopausal osteoporosis;
      however, the underlying pathological molecular mechanisms of its action remain
      unclear. In the present study, the alendronate-treated signaling pathway in bone
      metabolism in rats with ovariectomy induced by osteoporosis was investigated.
      Rats with osteoporosis were orally administered alendronate or phosphate-buffered
      saline (control). In addition, the interferon-beta (IFN-beta)/signal transducer
      and activator of transcription 1 (STAT1) signaling pathway was investigated in
      osteoblasts following treatment with alendronate in vitro and in vivo. During the
      differentiation period, IFN-beta (100 ng/ml) was used to treat the osteoblast
      cells, and the activity, viability and bone metabolism-associated gene expression
      levels (STAT1, p-STAT1, Fra1, TRAF6 and SOCS1) were analyzed in osteoblast cells.
      Histopathological changes were used to evaluate osteoblasts, osteoclasts,
      inflammatory phase of bone healing and osteonecrotic areas. The results
      demonstrated that alendronate significantly inhibited the activity of
      osteoporotic osteoclasts by stimulating expression of IFN-beta, as well as
      markedly improved the viability and activity of osteoblasts compared with the
      control group. In addition, alendronate increased the expression and
      phosphorylation levels of STAT1 in osteoclasts, enhanced osteoblast
      differentiation, upregulated the expression levels of alkaline phosphatase and
      osteocalcin, and increased the expression of osteoblast differentiation
      associated genes (osteocalcin, osterix and Runx2). Inhibition of IFN-beta
      expression canceled the benefits of alendronate-mediated osteoblast
      differentiation. Notably, alendronate enhanced bone formation in rats with
      osteoporosis induced by ovariectomy. In conclusion, these findings suggest that
      alendronate can regulate osteoblast differentiation and bone formation in rats
      with osteoporosis induced by ovariectomy through upregulation of IFN-beta/STAT1
      signaling pathway.

PMID- 29375682
TI  - Long non-coding RNA MDC1-AS inhibits human gastric cancer cell proliferation and
      metastasis through an MDC1-dependent mechanism.
AB  - Gastric cancer is the third leading cause of cancer-associated mortality
      worldwide and is one of the most common malignancies in China. However, the
      molecular mechanisms underlying the tumorigenesis of gastric cancer remain
      largely unclear. Long non-coding (Lnc)RNAs have been demonstrated to serve
      significant roles in the tumorigenesis of various types of cancer. The present
      study aimed to explore the role of the LncRNA mediator of DNA damage checkpoint
      protein 1-antisense RNA (MDC1-AS), the antisense transcript of MDC1, in human
      gastric cancer. The results revealed that the expression of MDC1-AS in human
      gastric cancer was significantly suppressed in vivo and in vitro. In addition,
      overexpression of MDC1-AS in the poorly differentiated gastric cancer cell line
      MKN28 significantly inhibited cell proliferation and metastasis, while the
      knockdown of MDC1-AS in well-differentiated MKN45 gastric cancer cells
      significantly increased proliferation and metastasis. The knockdown of MDC1
      relieved the inhibitory effect of MDC1-AS on MKN28 cell proliferation and
      metastasis, while the overexpression of MDC1 attenuated the stimulatory effect of
      MDC1-AS knockdown in MKN45 cells. Thus, the present study demonstrated that MDC1
      AS had an inhibitory on gastric tumorigenesis through an MDC1-dependent
      mechanism. This indicates that MDC1-AS is a potential novel therapeutic target
      for the diagnosis and treatment of human gastric cancer in the clinic.

PMID- 29375683
TI  - Toll-like receptor 2 downregulates the cholesterol efflux by activating the
      nuclear factor-kappaB pathway in macrophages and may be a potential therapeutic
      target for the prevention of atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease, which is triggered by lipid
      retention. Toll-like receptor 2 (TLR2) is a novel target for therapeutic
      intervention in atherosclerosis. In addition, nuclear factor-kappaB (NF-kappaB)
      serves important roles in stress response and inflammation. The present study
      investigated whether TLR2 is involved in the activation of cholesterol efflux in
      macrophages by regulating the NF-kappaB pathway. The human monocytic THP-1 cell
      line and murine macrophage RAW264.7 cell line were treated with 50 ug/ml oxidized
      low-density lipoprotein (ox-LDL) for 48 h in order to obtain macrophage foam
      cells. The cholesterol efflux of the cell lines under exogenous TLR2 treatment
      was assessed by liquid scintillation counting. Furthermore, the protein and mRNA
      expression levels of ATP binding cassette transporter A1 (ABCA1), ABCG1 and
      scavenger receptor B1 (SR-B1) were examined by western blot and quantitative
      polymerase chain reaction assays, respectively. To detect the effect of NF-kappaB
      on cholesterol efflux, the cells were divided into three groups, including the
      control, 10 ng/ml lipopolysaccharides (LPS; 24 h) and 10 ng/ml LPS + 50 uM
      pyrrolidinedithiocarbamate (PDTC; 24 h) groups. The results indicated that ox-LDL
      induced foam cell formation in the THP-1 and RAW264.7 cells, while TLR2
      significantly decreased the cholesterol efflux in dose- and time-dependent
      manners. Accordingly, TLR2 reduced ABCA1, ABCG1 and SR-B1 expression at the
      transcriptional and translational levels in a dose-dependent manner. In addition,
      application of PDTC (an NF-kappaB specific inhibitor) markedly suppressed the LPS
      induced downregulation of cholesterol efflux. These data revealed that TLR2 may
      be involved in the activation of cholesterol efflux in macrophages by regulating
      the NF-kappaB signaling pathway.

PMID- 29375684
TI  - Herba Gelsemii elegantis is detoxified by ramulus et folium Mussaendae
      pubescentis extract by modulating hepatic cytochrome P450 and glutathione S
      transferase enzymes in rats.
AB  - Herba Gelsemii elegantis (GE) has been frequently used as a Chinese folk medicine
      but has high acute toxicity. In Traditional Chinese Medicine, it may be
      detoxified by Ramulus et Folium Mussaendae pubescentis (MP), but the
      detoxification mechanism has remained elusive. The present study aimed to
      evaluate the detoxification mechanisms by which MP modulates the effect of GE in
      rats, including the inhibition of hepatic cytochrome P (CYP)450 and glutathione S
      transferase (GST) enzymes. Male Sprague Dawley rats were orally administered GE
      at three doses (0.36, 0.43 or 0.54 g/kg) alone and, at the highest dose, in
      combination with MP (21.6 g/kg) every day for 7 consecutive days. The control
      group of animals received the same volume of saline. The mRNA and protein
      expression of hepatic CYPs representative of two subfamilies (CYP2E1 and CYP1A2)
      were separately assessed by reverse-transcription quantitative polymerase chain
      reaction (RT-qPCR), western blot and immunohistochemistry assays. The mRNA and
      protein expression as well as enzyme activity of hepatic GST were assessed by RT
      qPCR, western blot and colorimetric assays, respectively. The results indicated
      that GE significantly inhibited CYP2E1 mRNA and protein expression in a dose
      dependent manner. Co-administration of MP increased CYP2E1 mRNA and protein
      expression as compared with the high GE dose alone. Cells expressing CYP2E1,
      located around the hepatic vascular plexus under a clear background, were
      identified by immunohistochemical staining. The results for CYP1A2 were similar
      to those for CYP2E1. At all concentrations used, GE significantly inhibited GST
      mu 1 (GSTm1) mRNA and protein expression in a dose-dependent manner, as compared
      with the control. Combination of GE and MP increased the mRNA and protein
      expression of GSTm1 as compared with the high dose of GE. However, the
      differences in GST-pi mRNA and protein expression between the GE and GE + MP
      groups were not significant. Of note, rats co-treated with MP were significantly
      protected from the decrease in GST activity produced by GE. The present study
      indicated that co-administration of GE and MP upregulated the activities of
      CYP450 and GST enzymes when compared with GE alone. This modulation may explain
      for the effect of MP in reducing the acute toxicity of GE.

PMID- 29375685
TI  - BNIP3/Bcl-2-mediated apoptosis induced by cyclic tensile stretch in human
      cartilage endplate-derived stem cells.
AB  - The present study aimed to investigate the molecular mechanisms of cyclic stretch
      induced apoptosis in human intervertebral disc cartilage endplate-derived stem
      cells (CESCs). CESCs were stretched by the Flexercell-4000TM Tension Plus system,
      the effect on cell viability was measured by a Cell Counting Kit-8 assay, while
      cell apoptosis was detected by flow cytometry. Western blot analysis was used to
      evaluate the expression of B-cell lymphoma 2 (Bcl-2)/adenovirus E1B 19 kDa
      interacting protein 3 (BNIP3), Bcl-2, Bcl-2 homologous antagonist killer (Bak),
      Bcl-2-associated X protein (Bax), Bcl extra large (Bcl-xl) and the activity of
      caspase-3, while Z-VAD-FMK was used to inhibit caspase-3. Compared with the
      control group, the cell viability decreased in a time-dependent manner after
      stretching. Furthermore, cell apoptosis and the activity of caspase-3 were
      increased in a time-dependent manner. The ratio of pro-death factor BNIP3 to anti
      apoptotic protein Bcl-2 was significantly increased. When cells were stretched
      for 36 h, the apoptosis-associated proteins Bak and Bax were increased, while Bcl
      xl was decreased. The viability and apoptotic ratio of stretched cells were
      significantly restored after caspase-3 was repressed. In conclusion, cyclic
      tensile stretch induced apoptosis of CESCs, which was probably due to
      upregulation of the expression of BNIP3.

PMID- 29375686
TI  - Correlation between RAGE gene promoter methylation and diabetic retinal
      inflammation.
AB  - The methylation status of the receptor for advanced glycation end products (RAGE)
      gene promoter in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic
      retinopathy (DR) patients was evaluated to investigate the correlation between
      RAGE gene promoter methylation and diabetic retinal inflammation. Eighty patients
      admitted and diagnosed as type 2 DR in Qilu Hospital, Shandong University during
      the period from October, 2013 to October, 2015 were enrolled in this study. They
      were the observation group and 40 healthy subjects were enrolled in the control
      group. PBMCs were collected from patients using density gradient centrifugation,
      and the methylation status of RAGE gene promoters was detected using methylation
      specific PCP (MSP). Interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor
      alpha (TNF-alpha) levels of in the serum were measured using enzyme-linked
      immunosorbent assay (ELISA). PBMCs in patients with positive RAGE gene promoter
      methylation were isolated and cultured and RAGE gene promoter methylation was
      inhibited using the demethylating agent, 5'-aza-2'-deoxycytidine (5-aza-dC). The
      methylation status of RAGE gene promoters in PBMCs was detected via MSP. IL
      1beta, IL-6 and TNF-alpha levels in the supernatant of PBMC culture solution were
      evaluated using ELISA. MSP results showed that there were 26 cases (32.50%) of
      RAGE gene promoter methylation in PBMCs in DR patients. RAGE gene promoters were
      methylated in all normal healthy subjects. IL-1beta, IL-6 and TNF-alpha levels in
      serum for positive RAGE gene promoter methylation group were significantly lower
      than those in negative RAGE gene promoter methylation group (p<0.01). 5-aza-dC
      inhibited the RAGE gene promoter methylation of PBMCs in patients with positive
      RAGE gene promoter methylation. The inhibition of methylation in RAGE gene
      promoter increased the levels of IL-1beta, IL-6 and TNF-alpha in supernatant of
      culture solution. In conclusion, RAGE gene promoter hypomethylation was detected
      in DR patients, indicating that RAGE gene promoter methylation could inhibit the
      diabetic retinal inflammation.

PMID- 29375688
TI  - The safety and efficacy of MPR-CTU combined with precise intraoperative
      ultrasonography guided flexible ureteroscope in the treatment of renal cystic
      disease.
AB  - The safety and efficacy of multi-planar reconstruction (MPR) image post
      processing technique-computed tomography (CT) urography (CTU) combined with
      precise intraoperative ultrasonography guided flexible ureteroscope in renal cyst
      incision and drainage in the treatment of cystic diseases of kidney were
      evaluated. A total of 68 patients were randomly divided into control and
      observation group (n=34). All the patients were treated with renal cyst incision
      and drainage under flexible ureteroscope. The control group was under ultrasound
      guidance. The observation group was combined with MPR-CTU, the safety and
      efficacy was compared. There was no significant difference between the two groups
      in the success rate and the time of cyst treatment (P>0.05). The incidence of
      intraoperative and postoperative complications of the observation group was
      significantly lower than that of the control group. After 1 month follow-up, the
      total effective rate of the observation group was significantly higher than that
      of the control group, the difference was statistically significant (P<0.05).
      Conclusion MPR-CTU technique combined with intraoperative ultrasonography to
      guide cyst incision and drainage under flexible ureteroscope for renal cystic
      disease has a high safety and efficacy, and it is worthy of clinical application.

PMID- 29375687
TI  - Morphological and molecular comparisons between tibialis anterior muscle and
      levator veli palatini muscle: A preliminary study on their augmentation
      potential.
AB  - Tibialis anterior (TA) muscle and other somite-derived limb muscles remain the
      prototype in skeletal muscle study. The majority of head muscles, however,
      develop from branchial arches and maintain a number of heterogeneities in
      comparison with their limb counterparts. Levator veli palatini (LVP) muscle is a
      deep-located head muscle responsible for breathing, swallowing and speech, and is
      central to cleft palate surgery, yet lacks morphological and molecular
      investigation. In the present study, multiscale in vivo analyses were performed
      to compare TA and LVP muscle in terms of their myofiber composition, in-situ stem
      cell population and augmentation potential. TA muscle was identified to be
      primarily composed of type 2B myofibers while LVP muscle primarily consisted of
      type 2A and 2X myofibers. In addition, LVP muscle maintained a higher percentage
      of centrally-nucleated myofibers and a greater population of satellite cells.
      Notably, TA and LVP muscle responded to exogenous Wnt7a stimulus in different
      ways. Three weeks after Wnt7a administration, TA muscle exhibited an increase in
      myofiber number and a decrease in myofiber size, while LVP muscle demonstrated no
      significant changes in myofiber number or myofiber size. These results suggested
      that LVP muscle exhibits obvious differences in comparison with TA muscle.
      Therefore, knowledge acquired from TA muscle studies requires further testing
      before being applied to LVP muscle.

PMID- 29375689
TI  - Treatment of glaucomatous optic nerve damage using ginsenoside Rg1 mediated by
      ultrasound targeted microbubble destruction.
AB  - The treatment of glaucomatous optic nervedamage using ginsenoside Rg1 mediated by
      ultrasound targeted microbubbles destruction was evaluated. Thirty healthy New
      Zealand white rabbits were subjected to injection of 0.3% carbomer solution to
      establish glaucomatous optic nerve damage model. Rabbits were divided into 5
      groups: control group, model group, model group + intravitreal injection of nerve
      growth factor (NGF) group, model group + intravitreal injection of ginsenoside
      Rg1 group (Rg1 group), model group + intravitreal injection of ginsenoside Rg1 +
      ultrasound microbubble group (ultrasound group), model group + ultrasound
      targeted microbubble destruction (ultrasound group). Intraocular pressures were
      compared at 1, 2 and 4 weeks after model establishment. Rabbits were sacrificed 4
      weeks after model establishment to collect retinal tissue for H&E staining.
      Histological changes were observed and the retinal thickness was measured.
      Contents of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide
      (NO) were measured by ELISA. Intraocular pressure was significantly higher in
      model group than in control group at 1 week (P<0.05). Intraocular pressure was
      significantly lower in the ultrasound group than in NGF group and Rg1 group at
      all time-points (P<0.05). The number of ganglion cells in model group was
      decreased significantly. Number of nuclear layer cells was significantly reduced.
      Thickest retina was found in control group and model group was the thinnest
      (P<0.05). Contents of MDA and NO in model group were significantly higher than
      those in NCF group and Rg1 group. SOD content in control group was higher than
      that in ultrasound group and model group (P<0.05). In conclusion, treatment of
      glaucomatous optic nerve damage using ginsenoside Rg1 mediated by ultrasound
      targeted microbubble destruction can reduce the level of oxidative stress,
      relieve intraocular pressure and reduce ganglion cell damage.

PMID- 29375690
TI  - Effect of SLC34A2 gene mutation on extracellular phosphorus transport in PAM
      alveolar epithelial cells.
AB  - A mutation in the IIb sodium phosphate transporter SLC34A2 gene has recently been
      described in pulmonary alveolar microlithiasis (PAM) patients. Experiments in
      this study were aimed at confirming the role of the gene product in PAM by
      comparing phosphorylated products in extracellular fluid of alveolar epithelial
      cells overexpressing the SLC34A2 gene or its mutated version. Eukaryotic
      expression vectors were constructed and transfected into A549 human alveolar
      epithelial cells. There were three groups of cells including those transfected
      with empty vector plasmid pcDNA3.1(+) (plasmid control group), those transfected
      with normal SLC34A2 gene expressed from pcDNA3.1 (normal control group), and
      those transfected with a version of the PAM SLC34A2 gene linked to the
      pcDNA3.1(+) (PAM group). Transfection efficiencies were detected by reverse
      transcription-polymerase chain reaction (RT-PCR). At 48 h after transfection, the
      concentration of inorganic phosphorus in the culture medium was detected using an
      automatic biochemical analyzer. Our results showed the concentration of inorganic
      phosphorus in the supernatant of the normal control group was significantly lower
      than that in the plasmid control and PAM groups (P<0.01), and the concentration
      in the PAM group was significantly lower than that in the plasmid control group
      (P<0.01). Based on our findings it is possible that the SLC34A2 gene mutation is
      the cause of the pathogenic changes observed in PAM patients, given that the
      function of the phosphate transporter seems to be affected and it is conceivable
      that it would lead to extracellular fluid alterations in vivo.

PMID- 29375692
TI  - Management of upper urinary tract calculi in crossed fused renal ectopic anomaly.
AB  - The aim of the present study was to summarize the management of upper urinary
      tract calculi in crossed fused renal ectopia (CFRE). Two patients were
      retrospectively studied in Xiangya Hospital (Changsha, China) and all relevant
      literature published in English between 1996 and 2016 was reviewed. All patients,
      including those reported in the literature, were characterized by age, sex,
      manifestation, therapy history, ectopic side, stone location, surgery and
      outcome. The patients had a mean age of 42.3+/-18.5 years, a male: Female ratio
      of 5:4 and the ratio of renal ectopic side was 9:8 (left:right). All patients
      suffered from different degrees of pain on the affected side, with or without
      hematuria. Up to 89% of patients presented with renal stones. These patients
      received treatments including conservative management in 2, extracorporeal shock
      wave lithotripsy (ESWL) in 2, percutaneous nephrolithotomy (PCNL) in 11,
      laparoscope nephrolithotomy in 1 and retrograde intrarenal surgery (RIRS) in 3.
      Complete stone clearance was achieved in 14 patients (73.7%). In addition, 3
      patients had a history of failed ESWL. No obvious intraoperative or postoperative
      complications occurred. The results suggested that, for the treatment of CFRE
      with upper urinary tract calculi, conservative treatment and ESWL are
      insufficient. PCNL is a safe and effective treatment for renal calculus, and
      laparoscopic nephrolithotomy is an alternative choice for treating large or
      staghorn renal stones. RIRS may become the first line of treatment for renal
      stones (<=3.5 cm) due to its multiple merits, including higher stone-free rates,
      minimal invasion and fewer complications.

PMID- 29375693
TI  - Simvastatin improves intracerebral hemorrhage through NF-kappaB-mediated
      apoptosis via the MyD88/TRIF signaling pathway.
AB  - The aim was to investigate the neuroprotective effects and potential mechanism
      mediated by simvastatin in a mouse model of intracerebral hemorrhage. CD-1 mice
      were subjected to infusion of collagenase type IV into the left striatum in order
      to induce intracerebral hemorrhage. Western blot analysis, the TUNEL assay and
      the modified neurological severity score were used in the present study to
      analyze the efficacy of simvastatin for intracerebral hemorrhage. The results
      demonstrated that simvastatin treatment improved the cerebral water content and
      blood-brain barrier disruption in the intracerebral hemorrhage animals.
      Intracerebral hemorrhage-induced neuronal cell death was downregulated by
      simvastatin treatment compared with the vehicle-treated model group. In addition,
      the expression levels of aquaporin-4, matrix metallopeptidase 9 and caspase-3
      were downregulated and B-cell lymphoma-2 was upregulated by simvastatin treatment
      compared with the vehicle-treated model. Simvastatin treatment also significantly
      reduced the Evans blue leakage into the injured hemispheres and improved motor
      function. Mechanism analysis further indicated that simvastatin treatment
      downregulated nuclear factor (NF)-kappaB expression, and upregulated the myeloid
      differentiation primary response 88 (MyD88) and TIR domain-containing adaptor
      protein inducing interferon-beta (TRIF) expression levels in neuronal cells in
      experimental mice. Furthermore, the results revealed that NF-kappaB
      overexpression abolished the simvastatin-downregulated MyD88 and TRIF expression
      levels, as well as the apoptosis of neuronal cells. In conclusion, these results
      indicated that simvastatin was able to attenuate brain edema and reduce cellular
      apoptosis by suppressing the NF-kappaB-mediated MyD88/TRIF signaling pathway
      subsequent to the induction of intracerebral hemorrhage in mice.

PMID- 29375691
TI  - Synergistic neuroprotective effects of Geniposide and ursodeoxycholic acid in
      hypoxia-reoxygenation injury in SH-SY5Y cells.
AB  - Endoplasmic reticulum stress (ERS) and autophagy activation play important roles
      in the process of cerebral ischemia/reperfusion (I/R) injury. The synergistic
      protective effects of Geniposide and ursodeoxycholic acid against cellular
      apoptosis caused by oxygen-glucose deprivation-reoxygenation (OGD/R) were
      investigated using a Cell Counting Kit-8 assay, lactate dehydrogenase (LDH)
      assay, flow cytometry, quantitative polymerase chain reaction (qPCR), and western
      blotting to examine cellular viability, apoptosis, reactive oxygen species (ROS)
      levels, mRNA and protein levels, respectively, in relation to ERS and autophagy.
      We found that pretreatment with Geniposide improved cellular viability. Moreover,
      treatment with a combination of Geniposide and Tauroursodeoxycholic acid (TUDCA)
      (GT) protected injured cells better than Geniposide alone. Further studies showed
      that the increase in cellular ROS levels, and the overexpression of mRNA and
      proteins related to OGD/R-induced ERS and autophagy, were both counteracted by
      GT. Our study indicates that the protective effects of GT on OGD/R-induced
      apoptosis in SH-SY5Y cells are associated with the inhibition of ERS and
      autophagy.

PMID- 29375694
TI  - Histological study of postnatal development of mouse tongues.
AB  - Numerous factors, including trauma, tumors and myophagism, may lead to tongue
      defects, which are mostly repaired via muscular flaps. However, these methods
      cannot restore the muscular function and gustation function of the tongue.
      Intensive research on tongue development may offer useful clues for tongue
      regeneration based on tissue engineering or stem cell therapy. In the present
      study, staining results revealed that tongue muscle fibers became larger, mature
      and stronger, and the foliate and fungiform papillae also became mature from
      newborn to adult C57BL/6J genetic background mice. Immunofluorescence staining
      and polymerase chain reaction results revealed that C-kit was dynamically
      expressed in muscle cells, as well as in foliate and fungiform papilla cells from
      newborn to adult stages. The expression level decreased from P1 to P15 and
      increased at P90. The immunofluorescence staining results revealed that Ki-67 was
      expressed in muscle cells and papilla cells from newborn to adult stages, and
      high expression was observed at P6 and P15. In addition, the immunofluorescence
      staining results also demonstrated that msh homeobox 2 (Msx2) was dynamically
      expressed in postnatal tongue muscle cells; however, almost no expression was
      detected in papilla cells. There was relative high expression level of Msx2 at P1
      and P6 stages, but this gradually decreased from P15, and it was expressed
      primarily in the muscle cells located in the marginal zone of the tongue at P90.
      These findings suggest that the amount of c-kit-expressing precursor cells in
      tongue muscle and papilla cells increases to promote tongue development at the
      early postnatal stage and to maintain homeostasis and functional adaptation of
      the tongue in the adult stage. Furthermore, Msx2 may serve an important role in
      postnatal tongue muscle development. The present study also suggests that C-kit
      and Msx2 may be used as cell markers for postnatal tongue regeneration and self
      repair, and may provide an approach for developing treatment methods for tongue
      diseases with a postnatal onset.

PMID- 29375695
TI  - Influence of cartilage interstitial fluid on gene expression in cruciate ligament
      fibroblasts.
AB  - Loading of articular cartilage during motion squeezes the fluid from the
      cartilage, termed cartilage interstitial fluid (CIF), which was found to
      influence gene expression in synovial membrane cells. After crucial ligaments
      damage, these cells are exposed to synovial fluid containing factors released
      from articular cartilage; the aim of the present study was to establish the
      influence of CIF and factors present in CIF (CIF-like cocktails) on crucial
      ligament fibroblasts. CIF was squeezed from articular-epiphyseal cartilage
      complexes of newborn rats. Fibroblasts were obtained from crucial ligaments of
      adult rat knee joints. Cells were cultured in control medium, CIF and CIF-like
      cocktails, and the expression of selected genes was evaluated using quantitative
      PCR. CIF stimulated the expression of HAS1, HAS2, aggrecan, lubricin, MMP3, TIMP3
      and TGFbeta1. Expression of collagen type I, versican, MMP2, TIMP2, TNF and
      IL1beta was inhibited. The CIF-like cocktail stimulated HAS1, HAS2, collagen type
      I, versican, aggrecan, lubricin, TIMP1, TGFbeta1, IL1beta, IL6 and inhibited of
      MMP3 and TNF expression. Both agents exerted similar effects on the expression of
      HAS2, aggrecan, lubricin, TGFbeta1 and TNF. CIF contains inhibitory and
      stimulatory factors affecting gene expression in crucial ligament fibroblasts and
      some of them were not included in the CIF-like cocktail. Due to the powerful
      influence of CIF on crucial ligament fibroblasts and the synovial membrane,
      further studies on its composition are needed. An improved CIF like-cocktail
      could be applied in the treatment of various joint or tendon ailments.

PMID- 29375696
TI  - Epidemiological study of high-risk human papillomavirus infection in subjects
      with abnormal cytological findings in cervical cancer screening.
AB  - The present study aimed to determine the genotype and age distribution of high
      risk human papillomavirus (HR-HPV) and evaluate HPV-DNA in subjects with abnormal
      cervical cytology results by using crowd-based cervical cancer screening cytology
      data. The Thinprep liquid-based cytologic test (TCT) was performed from January
      2013 to January 2014 in the permanent residents of Liaocheng (China) aged 21-65
      years who were married or had sexual intercourse. The number of screened women
      totaled 20,017, among whom 937 had abnormal results, 785 of which were recalled.
      For subjects in the age range of 21-65 years, an HR-HPV typing test using the
      fluorescence hybridization method. Among the 785 cases with abnormal TCT
      findings, repeated testing identified atypical squamous cells of unknown
      significance/atypical glandular cells in 478, low-grade squamous intraepithelial
      lesions in 175, high squamous intraepithelial lesions in 127 and squamous cell
      carcinoma/adenocarcinoma in 5 cases. Among these types, infection rates of HR-HPV
      were 50.2, 77.1, 89.0 and 100%, respectively. Of the 785 cases with abnormal TCT
      results, 493 (62.8%) were HR-HPV-positive. A total of 16 types of HR-HPV were
      detected: HPV-16, -18, -31, -33, -35, -39, -45, -51-53, -56, -58, -59, -66, 68
      and 73. Subjects infected with >=2 types were defined as having a multi-type
      infection. The infection rate was high in the age groups of 26-30 and 51-55
      years, accounting for 87.7% (71/81) and 79.7% (51/64), respectively, while it was
      lower in the >55 years group at 28.6% (14/54). The top five types of HR-HPV
      (stated in a decreasing order regarding positivity rate) were HPV16 (21.5%,
      169/785), HPV52 (12.2%, 96/785), HPV58 (9.8%, 77/785), HPV33 (9.7%, 76/785) and
      HPV18 (7.5%, 59/785). Single-type infection was encountered in 45.0% (353/785)
      and multi-type infection in 17.8% (140/785), among which 98 cases had a two-type
      infection, 37 had a three-type infection, 2 had a four-type infection, 2 had a
      five-type infection and 1 case had a six-type infection. In the present study,
      differences in multi-type HR-HPV infection between groups with different TCT
      results were statistically significant. In conclusion, compared with CTC
      screening on its own, complementary HR-HPV testing is an effective method for
      screening for cervical cancer. The infection rate of HPV16, -52, -58, -33 and -18
      was high among patients with cervical cytological abnormalities. Multi-type
      infection adds to the risk of malignancies. In Liaocheng, high-risk groups were
      aged 26-30 and 51-55. Attention should be paid during the screening and follow-up
      visits of these groups.

PMID- 29375698
TI  - An oral formulation of cilostazol nanoparticles enhances intestinal drug
      absorption in rats.
AB  - Cilostazol (CLZ) is an anti-platelet agent that is generally used after the onset
      of cerebral infarction. However, CLZ is a poorly water-soluble drug and a
      strategy for increasing its bioavailability is required. In the present study,
      novel oral formulations were designed containing CLZ solid nanoparticles to
      improve bioavailability. The present study investigated the therapeutic effect of
      the oral formulations containing CLZ nanoparticles on ischemic stroke using a
      cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice). The
      oral formulation containing CLZ nanoparticles (CLZ/Rnano tablet) was prepared
      using a combination of recrystallization and ball milling with the following
      ingredients: CLZ, docusate sodium, methylcellulose, 2-hydoxypropyl-beta
      cyclodextrin, gum arabic, polyvinylpyrrolidone, and mannitol. The particle size
      after re-dispersion of the CLZ/Rnano tablet was 64+/-47 nm (mean +/- standard
      deviation). The CLZ areas under the concentration-time curve (AUC) and mean
      residence time (MRT) in rats that were administered CLZ/Rnano tablets were
      significantly greater compared with those in rats that were administered
      CLZ/Rmicro tablets. Results indicated, the AUC after administration of CLZ/Rnano
      tablets was 3.1-fold higher compared with that after administration of the
      commercially available CLZ OD tablet. In addition, oral administration with
      CLZ/Rnano tablets ameliorated neurological deficits caused by ischemic stroke in
      MCAO/reperfusion mice. It is possible that the oral formulation containing CLZ
      nanoparticles will be useful for the treatment of patients with ischemic stroke
      and that these findings will provide significant information that can be used to
      improve the drug with low bioavailability.

PMID- 29375697
TI  - Primary chylopericardium: A case report and literature review.
AB  - Primary chylopericardium (CP) is a rare clinical condition in which chylous fluid
      containing high concentrations of triglyceride accumulates in the pericardial
      cavity. The present study reports a case of CP that was successfully treated by
      reconstruction surgery of thoracic duct. To improve the ability to diagnosis and
      treat this rare disease, the current study also systematically extracted 104
      reported cases of primary or idiopathic CP from the past 60 years (January 1950
      to December of 2015), and reviewed the clinical manifestation, etiology,
      diagnosis and treatment of these cases. The age at diagnosis varied between 6
      weeks and 79 years with a mean age of 27.95+/-16.50 years. Asymptomatic patients
      accounted for 39.42% of cases, while the most common initial symptoms were
      dyspnea (44.23%) and coughing (10.58%). Jugular venous distention and distant
      heart sound was identified in 23 (22.12%) and 34 cases (32.69%), respectively.
      Cardiomegaly in X-ray scans was detected in the majority of patients (93.27%). In
      addition, lymphoscintigraphy and lymphangiography were helpful in identifying the
      source of chyle. Regarding the etiology, idiopathic cases accounted for 35.56% of
      the included cases in the present study. The most important cause of primary CP
      was abnormal connection or accumulation of lymph fluid in the pericardium
      (37.50%). Conservative therapy included low-fat or medium-chain triglyceride
      diet, as well as total parenteral nutrition. The majority of patients (71.2%)
      required surgery for definitive therapy, and thoracic duct ligation was the most
      preferred surgical procedure, performed in 44.23% of cases. Follow-up was
      reported in 64 cases, and all patients survived during the mean follow-up period
      of 12 months. Therefore, it is suggested that surgical management is the most
      successful treatment method and is associated with a favorable prognosis.

PMID- 29375699
TI  - microRNA-503 suppresses the migration, proliferation and colony formation of
      prostate cancer cells by targeting tumor protein D52 like 2.
AB  - The present study investigated the expression of microRNA-503 (miR-503) and its
      effect and mechanism of action on prostate cancer. Tumor tissues and tumor
      adjacent tissues were collected from 20 patients with prostate cancer. TargetScan
      was used to predict the miRNA molecule that interacts with tumor protein D52 like
      2 (TPD52L2). DU145 cells were transfected with a negative control, miR-503 mimic
      or miR-503 inhibitor. DU145 cells that had not undergone transfection were used
      as a control. Levels of miR-503 and TPD52L2 mRNA were determined using reverse
      transcription-quantitative polymerase chain reaction and the expression of
      TPD52L2 protein was measured using western blot analysis. The migration ability
      of DU145 cells was evaluated using a Transwell assay and cell proliferation was
      examined using an MTT assay. A flat plate colony formation test was conducted to
      examine the colony formation rate of DU145 cells. The current study demonstrated
      that TPD52L2 expression is increased while miR-503 expression is decreased in
      prostate cancer tissues. Overexpression of miR-503 inhibited the transcription
      and translation of TPD52L2 in DU145 cells and reduced cell migration,
      proliferation and colony formation. By contrast, inhibition of miR-503 expression
      increased the expression of TPD52L2 in DU145 cells and increased cell migration,
      proliferation and colony formation. The present study demonstrated that miR-503
      is an oncogene that regulates the migration, proliferation and colony formation
      of prostate cancer cells by targeting the TPD52L2 gene. Thus, miR-503 has the
      potential to become a target for the molecular treatment and prognosis of
      prostate cancer in the future.

PMID- 29375700
TI  - Expression of miR-625 and Fas in cervical vertebral cartilage endplate.
AB  - The aim of the present study was to assess miR-625 and Fas expression in normal
      and degenerative cervical cartilage endplate (CEP) tissues. Following biof
      informatics analysis, the Fas gene was predicted to be one of the targets of miR
      625. Quantitative PCR (qPCR) and western blotting were used to detect miR-625 and
      Fas expression in normal and degenerative CEP. A luciferase reporter assay was
      used to identify whether miR-625 could directly target the 3' untranslated region
      (3'-UTR) of Fas. Lentiviral overexpression and/or inhibition vectors of miR-625
      (pre-miR-625)/antigomiR-625 were constructed to determine whether overexpression
      or inhibition of miR-625 could affect Fas and B-cell lymphoma 2 (Bcl-2)
      expression in cartilaginous endplate cells (CECs) and tissues. qPCR analysis
      demonstrated that miR-625 expression in degenerative CEP was significantly lower
      than in normal CEP tissue, while the production of Fas in degenerated CEP was
      significantly higher. Results from western blotting also showed a significant
      increase in Fas expression in degenerative CEP. miR-625 can bind directly to the
      3'-UTR of the Fas gene. However, this inhibition was attenuated by a target
      mutation in the miR-625-binding site of the 3'-UTR of Fas mRNA. In addition,
      following transfection of CECs with pre-miR-625 and antigomiR-625, expression of
      Fas significantly decreased and increased, respectively, and Bcl-2 expression was
      upregulated and downregulated, respectively. Upregulation of miR-625 can inhibit
      Fas expression and further affect Bcl-2 expression in CEP degeneration,
      suggesting that miR-625-mediated inhibition of the Fas gene is important in
      cervical degeneration.

PMID- 29375701
TI  - Monitoring of peripheral blood cluster of differentiation 4+ adenosine
      triphosphate activity and CYP3A5 genotype to determine the pharmacokinetics,
      clinical effects and complications of tacrolimus in patients with autoimmune
      diseases.
AB  - A total of 25 patients with autoimmune diseases receiving tacrolimus were
      screened using a peripheral blood cluster of differentiation 4+ adenosine
      triphosphate (ATP) activity assay (IMK assay) between October 2013 and July 2014.
      The autoimmune diseases of patients were as follows: Rheumatoid arthritis (n=15),
      lupus nephritis (n=6), ulcerative colitis (n=2) and myasthenia gravis (n=2).
      Patients were divided into two groups based on CYP3A5 genotype [expression of *1
      allele: Expressor (EX; n=6) and non-expressor (NEX; n=19)]. The tacrolimus
      concentration and concentration/dose ratio was significantly lower in the EX
      group compared with the NEX group (P=0.0108 and 0.0056, respectively). In
      addition, all enrolled patients that presented with adverse effects belonged to
      the NEX group. No significant associations were observed between IMK ATP levels
      and the concentration or dose of tacrolimus (P=0.1092 and 0.6999, respectively).
      However, the IMK ATP high-level group exhibited a significantly higher occurrence
      rate of insufficient effect when compared with the normal and low-level groups
      (P=0.0014). In conclusion, the clearance of tacrolimus in patients with
      autoimmune diseases was affected by the CYP3A5 genotype, as previously reported
      in organ transplant patients. The IMK ATP level may indicate the clinical
      response irrespective of tacrolimus concentration.

PMID- 29375702
TI  - Clinical efficacy of recombinant human latrophilin 3 antibody in the treatment of
      pediatric asthma.
AB  - Pediatric asthma is a chronic pulmonary inflammatory disease featuring
      hypersecretion of mucus and inflammation in the airway, resulting in dysfunction
      of the airway smooth muscle. Previous evidence demonstrated that latrophilins, a
      novel family of receptors, present a beneficial effect on airway smooth muscle
      cells. In the present study, the therapeutic effects of recombinant human
      latrophilin 3 (rhLPHN3) antibody (Ab) in patients with pediatric asthma were
      investigated, and the molecular mechanism underlying the function of LPHN3 in the
      treatment of asthma in clinical practice was examined. A total of 342 pediatric
      asthma cases were recruited and randomly divided into three groups, receiving
      treatment with rhLPHN3 Ab (n=134), salbutamol (n=108) or montelukast (n=100) by
      nasal aerosolization. Each group received the respective clinically tested dose
      for 16 weeks. Inflammatory factors interleukin (IL)-10, IL-17, IL-4, matrix
      metallopeptidase-9 (MMP-9), interferon-gamma (IFN-gamma) and transforming growth
      factor-beta (TGF-beta) levels in peripheral blood mononuclear cells were analyzed
      prior to and post treatment. The clinical outcomes revealed that pathological
      alterations were significantly improved following treatment with rhLPHN3 Ab for
      patients with pediatric asthma when compared with those receiving salbutamol and
      montelukast. It was also observed that rhLPHN3 Ab downregulated the plasma
      concentration levels of IL-10, IL-17, IL-4 and MMP-9, and upregulated IFN-gamma
      and TGF-beta levels in the three groups. In addition, clinical data demonstrated
      that rhLPHN3 Ab significantly promoted E-selectin and mucin 5AC expression, as
      well as improved the activation of nuclear factor (NF)-kappaB p65 DNA binding
      activity and the phosphorylation levels of protein kinase A. Furthermore, rhLPHN3
      Ab markedly improved adhesion and proliferation of airway smooth muscle cells,
      which led to promotion of the contraction of these cells. In conclusion, these
      clinical data suggest that rhLPHN3 Ab serves an important role in the inhibition
      of inflammatory mediators through downregulation of NF-kappaB signaling pathway,
      which contributes to airway remodeling and bronchodilation in patients with
      pediatric asthma.

PMID- 29375703
TI  - miR-30 decreases multidrug resistance in human gastric cancer cells by modulating
      cell autophagy.
AB  - Chemotherapy is an important treatment modality for gastric cancer, and multidrug
      resistance (MDR) represents a major obstacle for successful cancer chemotherapy.
      There is a lack of research on whether microRNA (miR)-30a regulation affects the
      chemosensitivity of resistant gastric cancer cells, and mechanisms underlying the
      effects of miR-30a on drug resistance and cell autophagy require further
      investigation. In the present study, the expression of miR-30a and its effects in
      cisplatin (CDDP)-resistant human gastric cancer cells were investigated. A CDDP
      resistant variant of the SGC-7901 cell line (SGC-7901/CDDP) was established by
      exposing the cells to gradually increasing drug concentrations, and miR-30a
      expression was detected by reverse transcription-semi quantitative polymerase
      chain reaction (RT-sqPCR). To examine the effect of miR-30a expression in the SGC
      7901/CDDP cells, miR30a mimics or negative control miRNA were transfected into
      the cells, and a Cell Counting Kit-8 assay was performed to analyze the
      chemosensitivity of the different cell groups. RT-sqPCR and western blot analysis
      were also used to measure MDR1 mRNA and P-glycoprotein expression, and the light
      chain (LC)3-II/LC3-I ratio. Furthermore, apoptosis induced by the
      chemotherapeutic CDDP in the different groups was assessed using flow cytometry.
      The results demonstrated that low expression of miR-30a was associated with
      chemoresistance in gastric cancer cells, and in the chemoresistant cell line
      SGC7901/CDDP, CDDP-induced apoptosis was weakened. Additionally, it was
      demonstrated that the LC3-II/LC3-I ratio was elevated in SGC7901/CDDP cells
      compared with chemosensitive SGC7901 cells (P<0.001), which could be attenuated
      by upregulating miR-30a expression (P<0.001 vs. SGC7901/CDDP control cells).
      These results suggested that autophagy may contribute to drug resistance in
      gastric cancer cells, and that the reduction of LC3-II in response to miR-30a
      overexpression may inhibit chemoresistance-associated autophagy in gastric cancer
      cells.

PMID- 29375704
TI  - Diagnosis and treatment of a carotid body tumor: A case report of a rare
      bilateral tumor.
AB  - In the present case report, a rare bilateral carotid body tumor (CBT) and the
      imaging and pathological features of a CBT are described. In the present report,
      a rare case of bilateral carotid body tumor, which developed in the bifurcation
      of the common carotid artery, and the clinical manifestations, imaging and
      pathological features of this CBT are summarized. The imaging cannot validate the
      diagnosis; however, imaging identified that the tumor exhibited an intact
      envelope. Immunohistochemical staining revealed that the tumor cells were
      strongly positive for cluster of differentiation 56, Syn and protein S-100,
      moderately positive for transcription factor E3, negative for cytokeratin and
      epithelial membrane antigen, and partial cells were weakly positive for Desmir
      (<5%). In view of the clinical and pathological features of the carotid body
      tumor, surgery is hypothesized to be the optimal treatment and may enable the
      tumor to be resected completely. Refined surgical techniques provide the security
      of safe resection and decrease the risk of complications occurring.

PMID- 29375705
TI  - Novel function of E26 transformation-specific domain-containing protein ELK3 in
      lymphatic endothelial cells.
AB  - Lymphatic endothelial cells (LEC) are major components of the tumor
      microenvironment and, due to the relative leakiness of lymphatic vessels compared
      with blood vessels, are essential for tumor dissemination and metastasis. In the
      present study, small interfering RNA-mediated suppression of E26 transformation
      specific domain-containing protein Elk-3 (ELK3) inhibited the proliferation,
      migration and tube-forming ability of LEC. Suppression of ELK3 decreased vascular
      endothelial-cadherin expression levels and increased the phosphorylation of beta
      catenin. Furthermore, vascular endothelial growth factor receptor-3 (VEGFR-3)
      mRNA and protein expression levels were suppressed by the transfection of LEC
      with siELK3. As VEGFR-3 serves a major role in lymphangiogenesis, ELK3 may be a
      novel therapeutic target to inhibit tumor dissemination through the lymphatic
      system.

PMID- 29375706
TI  - Gamma Knife Perfexion(r) radiosurgery and endo diode laser thermotherapy for
      choroidal melanoma with technical analysis: A case report.
AB  - Radiosurgery serves an important function in the treatment of patients with
      intraocular tumors and preserves visual function via organ conservation.
      Therefore, it is important to ensure the safety and precision of GK-SRS as a
      primary treatment for intraocular tumors. The present case study described a 57
      year-old female with uveal melanoma treated with GK-SRS. Retrobulbar anesthesia
      following fixation of the treated eye, via the suture of two of the extraocular
      muscles to the stereotactic frame, was performed to immobilize the eye during
      treatment. Computed tomography (CT) scans were performed following eye fixation,
      immediately prior to and following GK-SRS, to validate the accuracy of the tumor
      localization. The eye movement analysis revealed that the gravity center point
      deviations of the tumor and lens during treatment were <0.110 mm. At least 95% of
      the tumor volume was covered by the prescription dose according to three sets of
      CT images. The patient underwent a trans pars plana vitrectomy owing to a right
      eye vitreous hemorrhage. A 37-month follow-up assessment revealed tumor
      shrinkage, and the disappearance of the serous retinal detachments was noted on
      the basis of ophthalmoscopy and orbital magnetic resonance imaging. No major
      complications developed during the follow-up period. Using our treatment
      protocol, GK-SRS is a non-invasive procedure which is used as a brief single
      fraction treatment for intraocular tumor. The eye fixation method used in the
      present study has high accuracy.

PMID- 29375707
TI  - Effect of Ku80 on the radiosensitization of cisplatin in the cervical carcinoma
      cell line HeLa.
AB  - Cisplatin chemotherapy in combination with radiotherapy is the primary
      therapeutic strategy for the treatment of cervical cancer; however, the
      underlying molecular mechanism for cisplatin radiosensitization remains unknown.
      The aim of the present study was to investigate the effect of Ku80, a DNA double
      strand break (DSB) repair protein, on cisplatin radiosensitization in cervical
      cancer. The pre-established Ku80 suppression cervical cancer cell line HeLa/Ku80
      siRNA and the normal HeLa cell line underwent 6 MV X-ray irradiation (6 Gy)
      individually or in combination with 5 ug/ml cisplatin treatment. Alterations in
      apoptosis, the cell cycle and gammaH2AX expression were detected. Following
      irradiation individually and combined with cisplatin, compared with normal HeLa
      cells, HeLa/Ku80-siRNAexhibited an increased rate of apoptosis (P<0.05). It was
      identified that the earlier cisplatin was administered following irradiation, the
      higher the rate of apoptosis. Cell cycle analysis indicated that, following
      irradiation combined with cisplatin, the cells were arrested in G1 and S phase
      rather than in G2/M phase following irradiation alone. Microscopic imaging of
      immunofluorescence staining and western blotting identified that HeLa/Ku80-siRNA
      cells exhibited more gammaH2AX foci remaining following treatment with
      irradiation and cisplatin, particularly in the group treated with 6 Gy
      irradiation for 1 h together with 23 h of exposure to cisplatin. Irradiation in
      combination with cisplatin promoted the apoptosis of HeLa cells in association
      with the inhibition of Ku80, and it was identified that the earlier cisplatin was
      administered following irradiation, the more apoptosis was induced. This maybe
      because irradiation combined with cisplatin is able to arrest cells in G1 and S
      phase to rapidly repair damaged DNA, and the lack of Ku80 induces the inability
      to repair DSB, resulting in increased apoptosis. The results of the present study
      suggest that Ku80 may be a potent molecular target in cisplatin
      radiosensitization.

PMID- 29375708
TI  - TP53-induced glycolysis and apoptosis regulator is indispensable for mitochondria
      quality control and degradation following damage.
AB  - Mitochondria have been described as 'the powerhouse of the cell' as the organelle
      generates the majority of adenosine triphosphate (ATP) in cells to support life.
      Mitochondria can be damaged due to stress, for example by reactive oxygen species
      (ROS). TP53-induced glycolysis and apoptosis regulator (TIGAR) serves a role in
      suppressing ROS damage and may protect mitochondria integrity. In the present
      study, the localization of TIGAR on mitochondria in 5-8F cells was demonstrated.
      Furthermore, it was indicated that the knockdown of TIGAR using lentivirus-short
      hairpin RNA induces the loss of mitochondrial membrane potential and cytochrome c
      leakage. However, these damaged mitochondria were not degraded in cells, but
      exhibited an abnormal appearance as indicated by mitochondrial swelling, crista
      collapse and vacuolization, with physiological dysfunction marked by reduced ATP
      production. Therefore, TIGAR maybe an indispensable protein for mitochondrial
      protection and degradation following cellular damage.

PMID- 29375709
TI  - Puerarin inhibits bladder cancer cell proliferation through the mTOR/p70S6K
      signaling pathway.
AB  - Puerarin, as a novel oncotherapeutic agent, may exert anticancer effects and
      inhibit the proliferation of cancer cells. To explore the effects of puerarin on
      human bladder cancer cells, and to elucidate the potential mechanism underlying
      these effects, a Cell Counting Kit-8 assay was used to examine the proliferation
      of T24 and EJ cells following puerarin treatment. The effects of puerarin
      treatment on the cell cycle were detected by flow cytometry (FCM), while puerarin
      induced cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP
      nick end labeling and FCM, and the cellular ultrastructural morphological changes
      were observed by transmission electron microscopy. Cell invasion was examined
      using a Transwell assay with Matrigel. The expression levels of mechanistic
      target of rapamycin (mTOR), phosphorylated (p)-mTOR, p70-S6 kinase (p70S6K) and p
      p70S6K proteins in the mTOR signaling pathway were then assessed by western
      blotting. The results demonstrated that puerarin may inhibit bladder cancer cell
      viability, block the cell cycle in the G0/G1 phase and induce apoptosis in
      bladder cancer cells. The expression levels of p-mTOR and p-p70S6K proteins were
      downregulated, while no change was observed in the expression levels of mTOR and
      p70S6K proteins when T-24 and EJ cells were treated by puerarin. In the present
      study, puerarin was demonstrated to inhibit the viability of human bladder cancer
      cells. These effects may be due to the puerarin-induced downregulation of
      proteins in the mTOR/p70S6K signaling pathway, and the present study may provide
      the experimental basis for puerarin to be considered as a promising novel anti
      tumor drug for the treatment of bladder cancer.

PMID- 29375710
TI  - S100A11 promotes human pancreatic cancer PANC-1 cell proliferation and is
      involved in the PI3K/AKT signaling pathway.
AB  - S100A11, a member of S100 calcium-binding protein family, is associated with the
      numerous processes of tumorigenesis and metastasis. In the present study, the
      role of S100A11, and its possible underlying mechanisms in cell proliferation,
      apoptosis and cell cycle distribution in human pancreatic cancer were explored.
      Immunohistochemical analyses of S100A11 and phosphorylated (p)-AKT
      serine/threonine kinase (AKT) were performed in 30 resected specimens from
      patients with pancreatic cancer. PANC-1 cells were transfected with pcDNA3.1
      S100A11 or treated with 50 umol/l LY294002 for 48 h. Cell proliferation was
      determined using a cell counting kit-8 assay, whereas apoptosis and cell cycle
      distribution were determined by flow cytometry analysis. The mRNA and protein
      levels of S100A11, and AKT were determined using semi quantitative reverse
      transcription-polymerase chain reaction and western blot analyses, respectively.
      Pearson correlation analysis revealed that the expression levels of S100A11 and p
      AKT were positively correlated (r, 0.802; P<0.05). Compared with the control
      group, S100A11 overexpression significantly promoted PANC-1 cell proliferation
      and reduced the percentage of early apoptotic cells. Flow cytometric analysis
      indicated that the proportion of PANC-1 cells in the S phase was significantly
      elevated and cell percentage in the G0/G1 phase declined in response to S100A11
      overexpression (all P<0.05). S100A11 overexpression also significantly increased
      AKT mRNA and p-AKT protein expression levels (both P<0.05). The phosphoinositide
      3-kinase (PI3K) inhibitor, LY294002, significantly inhibited PANC-1 cell
      proliferation, promoted apoptosis and caused G1/S phase arrest in PANC-1 cells
      (all P<0.05). These findings together suggest that S100A11 promotes the viability
      and proliferation of human pancreatic cancer PANC-1 cells through the
      upregulation of the PI3K/AKT signaling pathway. Thus, S100A11 may be considered
      as a novel drug target for targeted therapy of pancreatic cancer.

PMID- 29375711
TI  - An option for delta-shaped gastroduodenostomy in totally laparoscopic distal
      gastrectomy for gastric cancer: A single-layer suturing technique for the stapler
      entry hole using knotless barbed sutures combined with the application of
      additional knotted sutures.
AB  - We report an option for delta-shaped gastroduodenostomy in totally laparoscopic
      distal gastrectomy (TLDG) for gastric cancer. We detail a single-layer suturing
      technique for the endoscopic linear stapler entry hole using knotless barbed
      sutures combined with the application of additional knotted sutures. From June
      2013 to February 2017, we performed TLDG with delta-shaped gastroduodenostomy in
      20 patients with gastric cancer. The linear stapler was closed and fired to
      attach the posterior walls of the remnant stomach and the duodenum together.
      After creating a good view of the greater curvature side of the entry hole for
      the stapler by retracting the knotted suture on the lesser curvature side toward
      the ventral side, we performed single-layer entire-thickness continuous suturing
      of this hole using a 15-cm-long barbed suture running from the greater curvature
      side to the lesser curvature side. We placed the second and third stitches
      between the seromuscular layer of the remnant stomach and the entire-thickness
      layer of the duodenum while suturing the duodenal mucosa as minutely as possible.
      In addition, we routinely added one or two entire-thickness knotted sutures at
      the site near the greater curvature side. We placed similar additional knotted
      sutures at the site with a broad pitch. TLDG with this reconstruction technique
      was successfully performed in all patients with no occurrences of anastomotic
      leakage or intraabdominal abscess around the anastomosis. It is suggested that
      this method can be one option for delta-shaped gastroduodenostomy in TLDG due to
      its cost-effectiveness and feasibility.

PMID- 29375712
TI  - MicroRNA-20a promotes proliferation and invasion by directly targeting early
      growth response 2 in non-small cell lung carcinoma.
AB  - MicroRNA-20a (miR-20a) serves a notable role in tumor development and
      progression; it functions differently in different types of malignant tumor, and
      its role and mechanism in non-small cell lung carcinoma (NSCLC) remains unclear.
      In the present study, the effects of miR-20a on the proliferation and invasion of
      NSCLC cells and the underlying mechanisms behind this were investigated. Reverse
      transcription-quantitative polymerase chain reaction revealed that the expression
      level of miR-20a was higher in human NSCLC than in normal tissues. Following
      this, the effect of miR-20a on the proliferation, apoptosis, migration and
      invasion of NSCLCA-549 cells was further evaluated. In vitro analysis, including
      a Cell Counting Kit-8, colony formation and Transwell migration assay, indicated
      that miR-20a-knockdown inhibited the proliferation, invasion and migration, while
      promoting the cell apoptosis of the A-549 cells. Early growth response 2 (EGR2)
      protein and mRNA levels were downregulated or upregulated following the
      overexpression or knockdown of miR-20a, respectively. Dual-luciferase reporter
      gene assays implied that EGR2 is a direct target gene of miR-20a. The results of
      the present study indicated that miR-20a may function as an oncomiR in the
      development of NSCLC by promoting cell viability and motility. The inhibition of
      miR-20a could even become a novel therapeutic method for the treatment of NSCLC.

PMID- 29375713
TI  - Identification of key genes associated with bladder cancer using gene expression
      profiles.
AB  - The aim of the present study was to further investigate the molecular mechanisms
      of bladder cancer. The microarray data GSE52519 were downloaded from Gene
      Expression Omnibus, comprising 9 bladder cancer and 3 normal bladder tissue
      samples. Differentially expressed genes (DEGs) were identified using Limma
      package analysis. Subsequently, Gene Ontology, Kyoto Encyclopedia of Genes and
      Genomes and Reactome pathway enrichment analyses were performed for down- and
      upregulated DEGs. Transcription factors and genes associated with cancer from
      DEGs were identified. Protein-protein interaction (PPI) networks were constructed
      using STRING, and pathway enrichment analysis was also conducted for genes in the
      core sub-network that was identified using BioNet. In total, 420 downregulated
      and 335 upregulated DEGs were identified. Functional and pathway enrichment
      analyses identified that a number of DEGs, including AURKA, CCNA2, CCNE1, CDC20
      and CCNB2, were enriched in the cell cycle. Furthermore, a total of 12
      upregulated proto-oncogenes were identified, including AURKA and CCNA2. In the
      PPI sub-network, a number of DEGs (e.g., CCNB2, CDC20, CCNA2 and MCM6) with
      higher degrees were enriched in the KEGG pathway of the cell cycle. In
      conclusion, the DEGs associated with the cell cycle (e.g., CDC20, CCNA2, CCNB2
      and AURKA) may serve pivotal roles in the pathogenesis of bladder cancer.

PMID- 29375714
TI  - Carcinoma associated fibroblasts derived from oral squamous cell carcinoma
      promote lymphangiogenesis via c-Met/PI3K/AKT in vitro.
AB  - Carcinoma-associated fibroblasts (CAFs) are dominant components of the tumor
      microenvironment (TME) that promote the development, progression and metastasis
      of cancer. c-Met is a receptor of the hepatocyte growth factor (HGF), which is
      involved in lymphangiogenesis. Currently, the roles of CAFs during
      lymphangiogenesis are unknown. It has been hypothesized that CAFs contribute to
      lymphangiogenesis of oral squamous cell carcinoma (OSCC) via a HGF/c-Met complex.
      The expression of HGF in OSCC was determined using CAFs derived from OSCC tissue
      and it was demonstrated that HGF is overexpressed in OSCC-derived CAFs. It was
      also revealed that c-Met was highly expressed in human lymphatic endothelial
      cells (HLECs) when co-cultured with CAFs. Furthermore, it was demonstrated that
      recombinant human HGF significantly enhanced the proliferation, migration,
      invasion and tube formation of HLECs. By contrast, the inhibition of c-Met
      expression suppressed the aforementioned biological activities and also
      downregulated the expression of c-Met, phosphoinositide 3-kinase and
      phosphorylated protein kinase B. Taken together, these data demonstrate that c
      Met is associated with the regulation of lymphangiogenesis. Thus, the results of
      the present study indicate that c-Met may be a promising novel therapeutic target
      to treat patients with OSCC.

PMID- 29375715
TI  - Dietary flavonoid tangeretin induces reprogramming of epithelial to mesenchymal
      transition in prostate cancer cells by targeting the PI3K/Akt/mTOR signaling
      pathway.
AB  - Tangeretin, a natural polymethoxyflavone present in the peel of citrus fruits is
      known to exhibit anticancer properties against a variety of carcinomas. Previous
      experimental evidence suggests that lifestyle and dietary habits affect the risk
      of prostate cancer to a certain extent. As the effect of tangeretin on prostate
      cancer is unexplored, the present study investigated the effect of tangeretin on
      androgen-insensitive PC-3 cells and androgen-sensitive LNCaP cells. Tangeretin
      reduced the cell viability of PC-3 cells in a dose- and time-dependent manner,
      with the half-maximal inhibitory concentration (IC50) observed at 75 uM dose
      following 72 h of incubation, while in LNCaP cells, the IC50 was identified to be
      ~65 uM. Expression levels of the mesenchymal proteins including vimentin, cluster
      of differentiation 44 and Neural cadherin in PC-3 cells were reduced by
      tangeretin treatment, whereas those of the epithelial proteins, including
      Epithelial cadherin and cytokeratin-19 were upregulated. Treatment of PC-3 cells
      also resulted in the downregulation of the phosphoinositide 3-kinase/protein
      kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway.
      Therefore, it may be concluded that tangeretin induces reprogramming of
      epithelial-mesenchymal transition in PC-3 cells by targeting the PI3K/Akt/mTOR
      signaling pathway.

PMID- 29375716
TI  - Sphingomyelin synthase 2 overexpression promotes cisplatin-induced apoptosis of
      HepG2 cells.
AB  - Hepatoblastoma (HB) is the most type of common pediatric liver cancer. The
      primary chemotherapy drug for HB is cisplatin (DDP). However, patients readily
      develop intrinsic and acquired resistance, and severe side effects to treatment.
      Sphingomyelin synthase 2 (SMS2) is a key enzyme involved in the generation of
      sphingomyelin (SM), which is able to regulate cell proliferation, apoptosis and
      differentiation. The death receptors (DRs) have important functions in DDP
      induced apoptosis. However, whether SMS2 is able to modulate cell apoptosis
      through the DR signaling pathway remains unknown. To investigate this question,
      SMS2 was overexpressed in HepG2 cells and treated with 3.5 mg/l cisplatin in the
      present study. After 24 h, the expression of SMS2, avian myelocytomatosis viral
      oncogene homolog (c-Myc), DR4, DR5 and caspase-3 was analyzed. Furthermore, cell
      viability was quantified, and apoptosis was assessed by western blot and flow
      cytometry analysis as well as Cell Counting kit-8. The results of the present
      study revealed that overexpression of SMS2 was able to increase the expression of
      c-Myc, cleaved caspase-3, DR4 and DR5 compared with the control group (P<0.05,
      n=3), and increase the levels of apoptosis in the SMS2 + DDP group, compared with
      the control (P<0.001, n=3). These results indicate that overexpression of SMS2 is
      able to improve sensitivity of HepG2 cells to DDP by increasing the expression of
      c-Myc, DR4 and DR5 in HepG2 cells. This increased sensitivity may decrease
      intrinsic and acquired resistance of chemotherapy in HB, and reduce the
      associated severe side effects in pediatric patients.

PMID- 29375717
TI  - Diagnosis, clinicopathological characteristics and prognosis of pulmonary
      mucinous adenocarcinoma.
AB  - Primary pulmonary mucinous adenocarcinoma (PPMA) is an uncommon subtype of lung
      adenocarcinoma. The present study attempted to clarify the diagnosis,
      clinicopathological characteristics, and pathologic significance of epithelial
      growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS)
      mutations and the prognosis of PPMA. A total of 29 patients with PPMA from among
      1,469 surgically resected patients with lung adenocarcinoma were enrolled. All of
      the tumours expressed CK7 and 5 cases exhibited co-expression with CK20. A total
      of 8 cases expressed EGFR, 14 cases expressed P53 and 2 cases expressed CEA. The
      majority of mucinous adenocarcinomas expressed thyroid transcription factor 1,
      Napsin A, Villin and Cam5.2 proteins. KRAS mutations were observed in 62% of
      patients and were more prevalent in the lower lung lobe and in patients with
      invasive mucinous adenocarcinoma. A total of 2 cases exhibited an EGFR mutation,
      and the co-mutation of KRAS and EGFR was only detected in 1 case. The relapse
      free and overall survival rates at 5 years were 70.4, and 81.5%, respectively.
      The results may assist to identify a molecular target and supply important
      information for a therapeutic strategy for patients with PPMA.

PMID- 29375718
TI  - Study on the diagnosis of small hepatocellular carcinoma caused by hepatitis B
      cirrhosis via multi-slice spiral CT and MRI.
AB  - The present study compared the diagnostic accuracy of multi-slice spiral computed
      tomography (CT) and magnetic resonance imaging (MRI) on small hepatocellular
      carcinoma (SHCC) caused by hepatitis B cirrhosis. A total of 160 patients with
      hepatitis B cirrhosis were selected between January 2012 and April 2016, and 183
      SHCC lesions were included in the present retrospective study. Patients were
      divided into the SHCC group (T stage) and the micro hepatocellular carcinoma
      (MHCC) group (T1 stage). There were a total of 129 SHCC lesions and 54 MHCC
      lesions identified. All patients underwent multiphasic CT and MRI imaging. The
      liver acquisition with volume acquisition (LAVA) technique was utilized for MRI.
      Furthermore, SPSS 20.0 was used for statistical analyses. LAVA in the arterial
      phase and CT in the arterial phase revealed significantly higher diagnostic rates
      for the diagnoses of 183 lesions. In addition, standard CT scan exhibited
      significantly reduced diagnostic rates in SHCC lesions. Results indicated that
      LAVA in the equilibrium phase had the lowest diagnostic rate in MHCC lesions,
      which was statistically significant (P<0.05). Overall, the diagnostic rate of CT
      (79.63%) for MHCC was significantly lower than that of MRI (96.29%) (P<0.05).
      However, the diagnostic rate of CT for SHCC (96.12%) was significantly higher
      than that for MHCC (79.63%) (P<0.05). MRI-LAVA in the arterial phase has the
      highest diagnostic rate for SHCC and MHCC. However, the diagnostic capability of
      MRI for MHCC lesions is superior to that of CT.

PMID- 29375719
TI  - Association of PHD3 and HIF2alpha gene expression with clinicopathological
      characteristics in human hepatocellular carcinoma.
AB  - Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3)
      serves a role in the progression and prognosis of cancer. PHD3 is able to induce
      apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and
      HIF2alpha were analyzed by western blot analysis and immunohistochemistry in 84
      paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver
      tissues. The mRNA levels of PHD3 and HIF2alpha were analyzed by reverse
      transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in
      HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001;
      protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The
      high level of expression of PHD3 in HCC tissues was associated with good
      differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small
      tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition,
      HIF2alpha expression was lower in HCC tissues compared with adjacent liver
      tissues (mRNA expression: P<0.001; protein expression: P=0.002;
      immunohistochemistry positive rate: P=0.002). No statistically significant
      associations were identified between HIF2alpha expression and clinicopathological
      characteristics. Pearson's and Spearman's correlation coefficients revealed no
      correlation between HIF2alpha and PHD3 expression in HCC. In conclusion, PHD3
      expression acts as a favorable prognostic marker for patients with HCC. There is
      no correlation between PHD3 and HIF2alpha expression in HCC.

PMID- 29375720
TI  - Propofol promotes apoptosis and suppresses the HOTAIR-mediated mTOR/p70S6K
      signaling pathway in melanoma cells.
AB  - Propofol is an intravenous anesthetic, which is widely used in clinical
      anesthesia induction and maintenance and is critical in the sedation of patients.
      However, the functions and mechanisms of propofol on apoptosis of melanoma cells
      remain unclear. The present study investigated whether propofol promotes cell
      apoptosis and suppresses the HOX transcript antisense RNA (HOTAIR)-mediated
      mechanistic target of rapamycin (mTOR) pathway in melanoma cells. B16F10 cells
      were cultured with different concentrations (0-10 uM) of propofol for 24 or 48 h.
      Proliferation and apoptosis of B16F10 cells were detected using MTT assay and
      flow cytometry. The pcDNA 3.1(-)-HOTAIR and pcDNA 3.1(-)-control plasmids were
      transfected into B16F10 cells using Lipofectamine 2000. In the present study,
      treatment with propofol significantly reduced viability, and induced apoptosis
      and caspase-3 activity in melanoma cells. Propofol treatment significantly
      inhibited HOTAIR expression and the expression of phosphorylated (p)-mTOR and p-
      p70S6K protein in melanoma cells. Overexpression of HOTAIR significantly
      increased viability of melanoma cells, and increased HOTAIR, p-mTOR and p-p70S6K
      protein expression in melanoma cells. These results indicated that propofol
      promotes apoptosis and suppresses the HOTAIR-mediated mTOR signaling pathway in
      melanoma cells.

PMID- 29375721
TI  - Dysregulation of miR-200 family microRNAs and epithelial-mesenchymal transition
      markers in oral squamous cell carcinoma.
AB  - MicroRNAs (miRNAs) are reported to function as a major component in the cellular
      signaling circuit, which regulates epithelial-mesenchymal transition (EMT).
      Dysregulation of the microRNA-200 (miR-200) family and EMT-associated genes
      enables tumor metastasis and resistance to therapy. The present study profiled
      miR-200 family members miR-200a, miR-200b, miR-200c, miR-141 and miR-429, and
      also several EMT-regulatory genes including zinc finger E-box-binding homeobox
      (ZEB)1, ZEB2, epithelial cadherin and vimentin in 40 oral primary tumors in order
      to understand their role(s) in oral squamous cell carcinoma (OSCC). The reverse
      transcription-quantitative polymerase chain reaction was used to analyze each
      sample. Results demonstrated a significant downregulation of miR-200 family
      members in tumors with a history of tobacco chewing/smoking (P<0.0006, P=0.0467,
      P=0.0014, P=0.0087 and P=0.0230, respectively) and undifferentiated pathology
      (miR-200a, P=0.0067; miR-200c, P=0.0248). EMT markers ZEB2 (P=0.0451) and
      vimentin (P=0.0071) were significantly upregulated in the oral tumors.
      Furthermore, ZEB2 antisense RNA1 was overexpressed in 50% of OSCC samples
      (P=0.0075). EMT-regulatory genes did not exhibit any association with clinical
      outcome. The present study also analyzed the expression of EMT-regulatory genes
      in 523 head and neck squamous cell carcinoma (HNSCC) samples from The Cancer
      Genome Atlas (TCGA) database, and the association with treatment outcome.
      Analysis of TCGA datasets also demonstrated no significant association in the
      expression of EMT markers with disease recurrence and treatment outcome. The
      results of the present study revealed dysregulation of miR-200 family miRNAs and
      EMT-regulatory genes in OSCC without any significant effect on treatment outcome.

PMID- 29375722
TI  - Correlations of GDF-15 with sST2, MMPs, and worsening functional capacity in
      idiopathic dilated cardiomyopathy: Can we gain new insights into the
      pathophysiology?
AB  - Growth and differentiation factor-15 (GDF-15) has been implicated in fibrosis,
      inflammation, and ventricular remodeling. The role of GDF-15 in the regulation of
      cardiac remodeling in idiopathic dilated cardiomyopathy (DCM) remains poorly
      defined. This study attempts to analyze the molecular interactions between GDF-15
      and markers of fibrosis as well as its positive correlations with worsening
      functional capacity. The study population consisted of 24 DCM patients and 8
      control subjects. All DCM patients had normal coronary angiographic studies.
      Plasma levels of GDF-15, matrix metalloproteinase-2 (MMP2), MMP3, MMP9, tissue
      inhibitor of MMP 1 (TIMP1), and soluble suppression of tumorigenicity-2 protein
      (sST2) were determined by enzyme-linked immunosorbent assays. Brain Natriuretic
      Peptide (BNP) was measured as per core laboratory protocol assay at Scott and
      White Memorial Hospital core laboratory. Correlation analysis was performed
      between GDF-15 and each of the MMPs-MMP2, MMP3, MMP9, and TIMP as well as New
      York Heart Association (NYHA) class and echocardiographic parameters (left
      ventricular ejection fraction (LVEF) and left ventricular internal dimension in
      diastole (LVIDd)). LVEF and LVIDd were obtained by two-dimensional
      echocardiography. The protocol was approved by Scott and White Memorial Hospital
      Institutional Review Board (S&W IRB). Correlation analysis of control versus all
      DCM patients showed a strong correlation of GDF-15 with TIMP1 (r = 0.83, p <
      0.0001) and weaker correlation with MMP3 (r = 0.41, p = 0.011) and MMP2 (r =
      0.47, p = 0.003). MMP9 showed poor correlation with GDF-15 (r = 0.3036, p =
      0.046). GDF-15 correlated negatively with MMP2/TIMP1 ratio (r = -0.47, p =
      0.006). sST2 correlated strongly with GDF-15 (r = 0.7, p < 0.0001). GDF-15
      correlated negatively with LVEF (r = -0.49, p = 0.004) and positively with LVIDd
      (r = 0.58, p = 0.0006). GDF-15 showed significant positive correlation with NYHA
      functional class (r = 0.71, p < 0.00001) and BNP (r = 0.86, p < 0.00001).
      Significant associations of GDF-15 with MMPs, sST2, LVIDd, LVEF, and NYHA class
      reported here for the first time in nonischemic dilated hearts may open up new
      avenues of investigations to better understand molecular mechanisms controlling
      cardiac remodeling. This study is limited by its small size and needs validation
      in larger populations.

PMID- 29375723
TI  - Liking More Means Doing More: Dispositional Attitudes Predict Patterns of General
      Action.
AB  - Dispositional attitudes are an individual difference in the tendency to form
      positive versus negative attitudes. As positive (negative) attitudes promote
      active (inactive) responses to stimuli, we predicted that dispositional attitudes
      would be positively correlated with patterns of general action. In Study 1,
      participants reported all activities they engaged in during a 1-week period using
      a structured time use survey. Dispositional attitudes were positively correlated
      with the number of unique behaviors participants engaged in and with the total
      number of behaviors reported for the entire week. Study 2 replicated Study 1
      using a free response time use survey. Overall, the results demonstrated that
      dispositional attitudes predict general action, such that the tendency to form
      positive (negative) attitudes predicts the tendency to engage in many (few)
      behaviors in daily life. This pattern occurred for both low effort and high
      effort behaviors. Implications for understanding activity patterns are discussed.

PMID- 29375724
TI  - The signature of liver cancer in immune cells DNA methylation.
AB  - Background: The idea that changes to the host immune system are critical for
      cancer progression was proposed a century ago and recently regained experimental
      support. Results: Herein, the hypothesis that hepatocellular carcinoma (HCC)
      leaves a molecular signature in the host peripheral immune system was tested by
      profiling DNA methylation in peripheral blood mononuclear cells (PBMC) and T
      cells from a discovery cohort (n = 69) of healthy controls, chronic hepatitis,
      and HCC using Illumina 450K platform and was validated in two validation sets (n
      = 80 and n = 48) using pyrosequencing. Conclusions: The study reveals a broad
      signature of hepatocellular carcinoma in PBMC and T cells DNA methylation which
      discriminates early HCC stage from chronic hepatitis B and C and healthy
      controls, intensifies with progression of HCC, and is highly enriched in immune
      function-related genes such as PD-1, a current cancer immunotherapy target. These
      data also support the feasibility of using these profiles for early detection of
      HCC.

PMID- 29375726
TI  - Fabrication of truly 3D microfluidic channel using 3D-printed soluble mold.
AB  - The field of complex microfluidic channels is rapidly expanding toward channels
      with variable cross-sections (i.e., beyond simple rounded channels with a
      constant diameter), as well as channels whose trajectory can be outside of a
      single plane. This paper introduces the use of three-dimensional (3D) printed
      soluble wax as cast molds for rapid fabrication of truly arbitrary microfluidic
      polydimethylsiloxane (PDMS) channels that are not achieved through typical soft
      lithography. The molds are printed directly from computer-aided design files,
      followed by simple dissolution using a solvent after molding PDMS, making rapid
      prototyping of microfluidic devices possible in hours. As part of the fabrication
      method, the solubility of several build materials in solvents and their effect on
      PDMS were investigated to remove the 3D-printed molds from inside the replicated
      PDMS microfluidic channels without damage. Technology limits, including surface
      roughness and resolution by comparing the designed channels with fabricated
      cylindrical channels with various diameters, are also characterized. We
      reproduced a 3D image of an actual human cerebral artery as cerebral artery
      shaped PDMS channels with a diameter of 240 MUm to prove the developed
      fabrication technique. It was confirmed that the fabricated vascular channels
      were free from any leakage by observing the fluorescence fluid fill.

PMID- 29375727
TI  - An in-situ photocrosslinking microfluidic technique to generate non-spherical,
      cytocompatible, degradable, monodisperse alginate microgels for chondrocyte
      encapsulation.
AB  - Alginate microgels are widely generated by ionic crosslinking methods, but this
      method has limitations in controlling the microgel degradation and generating non
      spherical microgels. By employing oxidized methacrylated alginate (OMA) that is
      degradable and photocrosslinkable, we have successfully photocrosslinked
      monodisperse OMA microgels and demonstrated the feasibility to generate discoid
      alginate microgels. However, several technical issues obstructed our opto
      microfluidic method from being a useful technique. Here, we further characterized
      and optimized this method. Monodisperse discoid OMA microgels with good shape
      consistency were, for the first time, generated. The curability of OMA microgels
      was characterized as the macromer concentration varied from 2% to 10%, and the
      minimum required photoinitiator (VA-086) concentrations were determined. The
      effects of crosslinking density and the presence of ions in the storage solution
      on swelling of OMA hydrogels were identified to give insights into accurate
      controlling of the microgel size. A much quicker degradation rate (within three
      weeks) compared to ionically crosslinked alginate hydrogels was indirectly
      identified by quantifying the elastic modulus using atomic force microscopy. The
      viability of encapsulated chondrocytes in OMA microgels formed by this method was
      higher than those from other existing methods, demonstrating its favorable
      cytocompatibility. It was found that the oxygen tension played a critical role in
      both the curability of microgels and the cytocompatibility of this technique. We
      also summarize common practical issues and provide related solutions and/or
      operational suggestions. By this method, OMA microgels are expected to be
      valuable alternatives to traditional ionically crosslinked alginate microgels in
      drug delivery, tissue engineering, and single cell analysis areas due to their
      multiple favorable properties.

PMID- 29375725
TI  - Four new C19-diterpenoid alkaloids from Delphinium elatum.
AB  - Diterpenoid alkaloids with remarkable chemical properties and biological
      activities are frequently found in plants of the genera Aconitum, Delphinium, and
      Garrya. Accordingly, several C19-diterpenoid alkaloid components from Delphinium
      elatum cv. Pacific Giant, as well as their derivatives, exhibited cytotoxic
      activity against lung, prostate, nasopharyngeal, and vincristine-resistant
      nasopharyngeal cancer cell lines. Four new C19-diterpenoid alkaloids, elapacigine
      (1), N-deethyl-N-formylpaciline (2), N-deethyl-N-formylpacinine (3), and N-formyl
      4,19-secoyunnadelphinine (4), together with 11 known C19-diterpenoid alkaloids
      were isolated in a phytochemical investigation on the seeds of D. elatum cv.
      Pacific Giant. Their structures were elucidated by extensive spectroscopic
      methods including NMR (1D and 2D), IR, and MS (HRMS). Three of the new C19
      diterpenoid alkaloids (2-4) and five of the known diterpenoid alkaloids were
      evaluated for cytotoxic activity against five human tumor cell lines.

PMID- 29375728
TI  - Steel reinforced composite silicone membranes and its integration to microfluidic
      oxygenators for high performance gas exchange.
AB  - Respiratory distress syndrome (RDS) is one of the main causes of fatality in
      newborn infants, particularly in neonates with low birth-weight. Commercial
      extracorporeal oxygenators have been used for low-birth-weight neonates in
      neonatal intensive care units. However, these oxygenators require high blood
      volumes to prime. In the last decade, microfluidics oxygenators using enriched
      oxygen have been developed for this purpose. Some of these oxygenators use thin
      polydimethylsiloxane (PDMS) membranes to facilitate gas exchange between the
      blood flowing in the microchannels and the ambient air outside. However, PDMS is
      elastic and the thin membranes exhibit significant deformation and delamination
      under pressure which alters the architecture of the devices causing poor
      oxygenation or device failure. Therefore, an alternate membrane with high
      stability, low deformation under pressure, and high gas exchange was desired. In
      this paper, we present a novel composite membrane consisting of an ultra-thin
      stainless-steel mesh embedded in PDMS, designed specifically for a microfluidic
      single oxygenator unit (SOU). In comparison to homogeneous PDMS membranes, this
      composite membrane demonstrated high stability, low deformation under pressure,
      and high gas exchange. In addition, a new design for oxygenator with sloping
      profile and tapered inlet configuration has been introduced to achieve the same
      gas exchange at lower pressure drops. SOUs were tested by bovine blood to
      evaluate gas exchange properties. Among all tested SOUs, the flat design SOU with
      composite membrane has the highest oxygen exchange of 40.32 ml/min m2. The
      superior performance of the new device with composite membrane was demonstrated
      by constructing a lung assist device (LAD) with a low priming volume of 10 ml.
      The LAD was achieved by the oxygen uptake of 0.48-0.90 ml/min and the CO2 release
      of 1.05-2.27 ml/min at blood flow rates ranging between 8 and 48 ml/min. This LAD
      was shown to increase the oxygen saturation level by 25% at the low pressure drop
      of 29 mm Hg. Finally, a piglet was used to test the gas exchange capacity of the
      LAD in vivo. The animal experiment results were in accordance with in-vitro
      results, which shows that the LAD is capable of providing sufficient gas exchange
      at a blood flow rate of ~24 ml/min.

PMID- 29375729
TI  - Fabrication and Characterization of In Situ Synthesized SiC/Al Composites by
      Combustion Synthesis and Hot Press Consolidation Method.
AB  - The in situ SiC/Al composites were fabricated in Al-Si-C systems with different
      Si/C mass ratios and holding time by the method of combustion synthesis and hot
      press consolidation. The influences of Si/C mass ratio and holding time on the
      phase constitution, microstructure, and hardness of the composites were
      investigated. The results indicate that the increase of Si/C mass ratio leads to
      more uniform size distribution of the SiC particles in the Al matrix. Moreover,
      by improving the Si/C mass ratio from 4 : 1 to 5 : 1, the maximum size of SiC
      particle was reduced from 4.1 MUm to 2.0 MUm. Meanwhile, the percentage of
      submicroparticles was increased from 22% to 63%, and the average hardness value
      of the composites was increased by 13%. In addition, when the holding time is set
      to be fifteen minutes, the Al4C3 phase did not exist in the composites because of
      its total reactions with Si atoms to form SiC particles, and the average hardness
      value was 73.8 HB.

PMID- 29375730
TI  - Inverse association between MDM2 and HUWE1 protein expression levels in human
      breast cancer and liposarcoma.
AB  - The ubiquitin E3 ligase MDM2 is best known for its ability to suppress the tumor
      suppressor p53. However, MDM2 also targets other proteins for proteasomal
      degradation and accumulating evidence strongly suggests p53-independent roles of
      MDM2 in cancer. We previously reported that MDM2 promotes degradation of another
      ubiquitin E3 ligase HUWE1 by ubiquitination, particularly, which confers HER2+
      breast cancer cells resistance to the HER2 inhibitor lapatinib. However, it
      remains unclear whether such a mechanism can operate in other cell types,
      independently of HER2 inhibitors. Moreover, in vivo evidence that supports HUWE1
      degradation by MDM2 is missing. In the current study, we performed
      immunohistochemistry (IHC) to analyze expression levels of MDM2 and HUWE1 in
      normal organs, two breast cancer cohorts (A, n = 137 and B, n = 27), and a
      liposarcoma cohort (n = 45). Our results show that HUWE1 is ubiquitously
      expressed in healthy organs, where the oncoprotein MDM2 is undetectable.
      Likewise, in the majority of breast cancers regardless of their subtypes, MDM2 is
      below detectable levels, while HUWE1 is highly expressed. In contrast, in a
      subset of liposarcoma that is characterized by MDM2 overexpression, only 40% of
      these showed detectable HUWE1 protein. Importantly, despite the inverse
      association between MDM2 and HUWE1 protein levels, gene expression analysis in
      independent datasets revealed no such correlation at the mRNA level. Our results
      demonstrate the first in vivo evidence to support the hypothesis of MDM2-mediated
      HUWE1 degradation, which may help to understand the regulation of HUWE1 as well
      as p53-independent roles of MDM2.

PMID- 29375732
TI  - Acute Trigger Finger Presenting as an Extensor Lag.

PMID- 29375731
TI  - Matrix Metalloproteinases Are Differentially Regulated and Responsive to
      Compression Therapy in a Red Duroc Model of Hypertrophic Scar.
AB  - Objective: Proteins of the matrix metalloproteinases family play a vital role in
      extracellular matrix maintenance and basic physiological processes in tissue
      homeostasis. The function and activities of matrix metalloproteinases in response
      to compression therapies have yet to be defined. Here, a swine model of
      hypertrophic scar was used to profile the transcription of all known 26 matrix
      metalloproteinases in scars treated with a precise compression dose. Methods:
      Full-thickness excisional wounds were created. Wounds underwent healing and scar
      formation. A subset of scars underwent 2 weeks of compression therapy. Biopsy
      specimens were preserved, and microarrays, reverse transcription-polymerase chain
      reaction, Western blotting, and immunohistochemistry were performed to
      characterize the transcription and expression of various matrix metalloproteinase
      family members. Results: Microarray results showed that 13 of the known 26 matrix
      metalloproteinases were differentially transcribed in wounds relative to the
      preinjury skin. The predominant upregulation of these matrix metalloproteinases
      during early wound-healing stages declined gradually in later stages of wound
      healing. The use of compression therapy reduced this decline in 10 of the 13
      differentially regulated matrix metalloproteinases. Further investigation of MMP7
      using reverse transcription-polymerase chain reaction confirmed the effect of
      compression on transcript levels. Assessment of MMP7 at the protein level using
      Western blotting and immunohistochemistry was concordant. Conclusions: In a swine
      model of hypertrophic scar, the application of compression to hypertrophic scar
      attenuated a trend of decreasing levels of matrix metalloproteinases during the
      process of hypertrophic wound healing, including MMP7, whose enzyme regulation
      was confirmed at the protein level.

PMID- 29375733
TI  - Optimizing Outcomes in Pedicle and Free Flap Reconstruction in Patients With
      Sickle Cell Trait.

PMID- 29375735
TI  - Confocal endomicroscopy and cyst fluid molecular analysis: Comprehensive
      evaluation of pancreatic cysts.
AB  - Increases in the quality as well as utilization of cross-sectional imaging have
      led to rising diagnoses of pancreatic cystic lesions (PCL). Accurate presurgical
      diagnosis enables appropriate triage of PCLs. Unfortunately, current diagnostic
      approaches have suboptimal accuracy and may lead to unnecessary surgical
      resections or missed diagnoses of advanced neoplasia. Additionally, early
      detection represents an opportunity for intervention to prevent the progression
      to pancreatic adenocarcinoma. Our aim for this review is to systematically review
      the current literature on confocal endomicroscopy and molecular biomarkers in the
      evaluation of PCLs. Confocal laser endomicroscopy is a novel technology that
      allows for real-time in vivo microscopic imaging with multiple clinical trials
      identifying characteristic endomicroscopy findings of various pancreatic cystic
      lesions. DNA-based molecular markers have also emerged as another diagnostic
      modality as the pattern of genetic alternations present in cyst fluid can provide
      both diagnostic and prognostic data. We propose that both techniques can be
      utilized to improve patient outcomes.

PMID- 29375736
TI  - Imaging of gall bladder by endoscopic ultrasound.
AB  - Endoscopic ultrasonography (EUS) is considered a superior investigation when
      compared to conventional ultrasonography for imaging gall bladder (GB) lesions as
      it can provide high-resolution images of small lesions with higher ultrasound
      frequencies. Examination of GB is frequently the primary indication of EUS
      imaging. Imaging during EUS may not remain restricted to one station and multi
      station imaging may provide useful information. This review describes the
      techniques of imaging of GB by linear EUS from three different stations. The
      basic difference of imaging between the three stations is that effective imaging
      from station 1 is done above the neck of GB, from station 2 at the level of the
      neck of GB and from station 3 below the level of the neck of GB.

PMID- 29375737
TI  - New 14-mm diameter Niti-S biliary uncovered metal stent for unresectable distal
      biliary malignant obstruction.
AB  - AIM: To investigate whether an uncovered self-expandable metal stent (UCSEMS)
      with a large diameter could prevent recurrent biliary obstruction (RBO). METHODS:
      Thirty-eight patients with malignant biliary obstruction underwent treatment with
      an UCSEMS with a 14-mm diameter (Niti-S 14). Retrospectively, we evaluated
      technical and functional success rate, RBO rate, time to RBO, survival time, and
      adverse events in these patients. RESULTS: Stent placement success and functional
      success were achieved in all patients. Two patients (5.3%) had RBO due to tumor
      ingrowth or overgrowth. The median time to RBO was 190 (range, 164-215) d. The
      median survival time was 120 (range, 18-502) d. The 6-mo non-RBO rate was 91%.
      Other adverse events other than RBO occurred as follows: Acute cholecystitis,
      post-ERCP pancreatitis, hemobilia, and fever without exacerbation of liver
      injury, and liver abscess in 4 (10.3%), 3 (7.9%), 2 (5.3%), 1 (2.6%), and 1
      (2.6%), respectively. Migration of the stents was not observed. CONCLUSION: Niti
      S 14 is considered to be a preferable metal stent because of a low rate of RBO
      with no migration.

PMID- 29375734
TI  - Linking Cancer Cachexia-Induced Anabolic Resistance to Skeletal Muscle Oxidative
      Metabolism.
AB  - Cancer cachexia, a wasting syndrome characterized by skeletal muscle depletion,
      contributes to increased patient morbidity and mortality. While the intricate
      balance between protein synthesis and breakdown regulates skeletal muscle mass,
      the suppression of basal protein synthesis may not account for the severe wasting
      induced by cancer. Therefore, recent research has shifted to the regulation of
      "anabolic resistance," which is the impaired ability of nutrition and exercise to
      stimulate protein synthesis. Emerging evidence suggests that oxidative metabolism
      can regulate both basal and induced muscle protein synthesis. While disrupted
      protein turnover and oxidative metabolism in cachectic muscle have been examined
      independently, evidence suggests a linkage between these processes for the
      regulation of cancer-induced wasting. The primary objective of this review is to
      highlight the connection between dysfunctional oxidative metabolism and cancer
      induced anabolic resistance in skeletal muscle. First, we review oxidative
      metabolism regulation of muscle protein synthesis. Second, we describe cancer
      induced alterations in the response to an anabolic stimulus. Finally, we review a
      role for exercise to inhibit cancer-induced anabolic suppression and
      mitochondrial dysfunction.

PMID- 29375738
TI  - Post-endoscopic procedure satisfaction scores: Can we improve?
AB  - AIM: To organize post-procedure satisfaction data into a useful reference and
      analyze patient-centered parameters to find trends that influence patient
      satisfaction. METHODS: A robust database of two cohorts of outpatients that
      underwent an endoscopic procedure at Georgetown University Hospital at two
      separate three-month intervals ranging from November 2012 to January 2013 and
      November 2015 to January 2016 was compiled. Time of year was identical to control
      for weather/seasonal issues that may have contributed to the patient experience.
      The variables recorded included age, sex, body mass index (BMI), type of
      procedure, indication for procedure, time of the procedure, length of the
      procedure, type of prep used, endoscopist, satisfactory score, and
      comments/reasons for score. For continuous variables, differences in averages
      were tested by two sample t-test, Wilcoxon rank sum test, and ANOVA as
      appropriate. For categorical variables, differences in proportions between two
      groups were tested by chi2 test. Correlation test and linear regression analyses
      were conducted to examine relationships between length of procedure and
      continuous predictors. A P value < 0.05 used to indicate statistically
      significant relationship. RESULTS: The primary outcome of this study was to
      assess if telephone outreach after an endoscopic intervention was a satisfactory
      method of obtaining post-procedure satisfaction scores from patients at a
      tertiary care center. With the addition of post-procedure calls, instilled in
      January 2014, the response rate was 40.5% (508/1256 patients) from a prior
      completion rate of 3.4% (31/918) with the mail out survey initially. There was a
      statistically significant improved response rate pre and post intervention with P
      < 0001. The secondary outcome of this study was to assess if we could use
      predictive analytics to identify independent predictors of procedure length, such
      as gender, age, type of procedure, time of procedure, or BMI. The combined pre
      and post intervention data was used in order to optimize the power to identify
      independent predictors of procedure length. The total number of patient's data
      analyzed was 2174. There was no statistically significant difference in procedure
      length between males and females with P value 0.5282. However, there was a small
      (1 min), but statistically significant difference (P = 0.0185) in procedure
      length based on the time of day the procedure took place, with afternoon
      procedures having a longer duration than morning procedures. The type of
      procedure was an independent predictor of procedure length as demonstrated with P
      value < 0.0001. There is a statistically significant correlation between age and
      procedure length, although it is only a weak relationship with a correlation
      coefficient < 0.3. Contrary to patient age, BMI did not have a statistically
      significant correlation with procedure length (P = 0.9993), which was also
      confirmed by linear regression analysis. CONCLUSION: Our study proves calling
      patients after endoscopy improves post-procedure satisfaction response rates and
      changing procedural time allotment based on patient characteristics would not
      change endoscopic workflow.

PMID- 29375739
TI  - Case series on multimodal endoscopic therapy for gastric antral vascular ectasia,
      a tertiary center experience.
AB  - AIM: To study and describe patients who underwent treatment for gastric antral
      vascular ectasia (GAVE) with different endoscopic treatment modalities. METHODS:
      We reviewed patients with GAVE who underwent treatment at University of Alabama
      at Birmingham between March 1, 2012 and December 31, 2016. Included patients had
      an endoscopic diagnosis of GAVE with associated upper gastrointestinal bleeding
      or iron deficiency anemia. RESULTS: Seven out of 15 patients had classic
      watermelon description for GAVE, 1/15 with diffuse/honeycomb pattern and 6/15
      with nodular GAVE per EGD description. Seven out of 15 patients required
      multimodal treatment. Four out of six of patients with endoscopically nodular
      GAVE required multimodal therapy. Overall, mean pre- and post-treatment
      hemoglobin (Hb) values were 8.2 +/- 0.8 g/dL and 9.7 +/- 1.6 g/dL, respectively
      (P <= 0.05). Mean number of packed red blood cells transfusions before and after
      treatment was 3.8 +/- 4.3 and 1.2 +/- 1.7 (P <= 0.05), respectively. CONCLUSION:
      Patients with nodular variant GAVE required multimodal approach more frequently
      than non-nodular variants. Patients responded well to multimodal therapy and saw
      decrease in transfusion rates and increase in Hb concentrations. Our findings
      suggest a multimodal approach may be beneficial in nodular variant GAVE.

PMID- 29375740
TI  - Mediastinal node staging by positron emission tomography-computed tomography and
      selective endoscopic ultrasound with fine needle aspiration for patients with
      upper gastrointestinal cancer: Results from a regional centre.
AB  - AIM: To investigate the impact of endoscopic ultrasound-guided fine-needle
      aspiration (EUS-FNA) and positron emission tomography-computed tomography (PET
      CT) in the nodal staging of upper gastrointestinal (GI) cancer in a tertiary
      referral centre. METHODS: We performed a retrospective review of prospectively
      recorded data held on all patients with a diagnosis of upper GI cancer made
      between January 2009 and December 2015. Only those patients who had both a PET-CT
      and EUS with FNA sampling of a mediastinal node distant from the primary tumour
      were included. Using a positive EUS-FNA result as the gold standard for lymph
      node involvement, the sensitivity, specificity, positive and negative predictive
      values (PPV and NPV) and accuracy of PET-CT in the staging of mediastinal lymph
      nodes were calculated. The impact on therapeutic strategy of adding EUS-FNA to
      PET-CT was assessed. RESULTS: One hundred and twenty one patients were included.
      Sixty nine patients had a diagnosis of oesophageal adenocarcinoma (Thirty one of
      whom were junctional), forty eight had oesophageal squamous cell carcinoma and
      four had gastric adenocarcinoma. The FNA results were inadequate in eleven cases
      and the PET-CT findings were indeterminate in two cases, therefore thirteen
      patients (10.7%) were excluded from further analysis. There was concordance
      between PET-CT and EUS-FNA findings in seventy one of the remaining one hundred
      and eight patients (65.7%). The sensitivity, specificity, PPV and NPV values of
      PET-CT were 92.5%, 50%, 52.1% and 91.9% respectively. There was discordance
      between PET-CT and EUS-FNA findings in thirty seven out of one hundred and eight
      patients (34.3%). MDT discussion led to a radical treatment pathway in twenty
      seven of these cases, after the final tumour stage was altered as a direct
      consequence of the EUS-FNA findings. Of these patients, fourteen (51.9%)
      experienced clinical remission of a median of nine months (range three to forty
      two months). CONCLUSION: EUS-FNA leads to altered staging of upper GI cancer,
      resulting in more patients receiving radical treatment that would have been the
      case using PET-CT staging alone.

PMID- 29375741
TI  - Management of endoscopic biliary stenting for choledocholithiasis: Evaluation of
      stent-exchange intervals.
AB  - AIM: To evaluate the best management of plastic stents in patients with
      choledocholithiasis who were unfit for endoscopic stone removal or surgery.
      METHODS: Between April 2007 and September 2017, 87 patients (median age 83.7
      years) with symptomatic choledocholithiasis were treated with insertion of 7-Fr
      plastic stents because complete endoscopic stone retrieval was difficult, and
      their general condition was not suitable for surgery. Seventy of these patients
      agreed to regular stent management and stent exchange was carried out at every 6
      mo (Group A, n = 35) or every 12 mo (Group B, n = 35). The remaining 17 patients
      did not accept regular stent exchange, and stents were replaced when clinical
      symptoms appeared (Group C). We evaluated the frequency of biliary complication
      and stent patency rate during follow-up periods. RESULTS: The patency rate of
      biliary plastic stents was 91.4% at 6 mo (Group A) and 88.6% at 12 mo (Group B),
      respectively. Acute cholangitis occurred in 2.9% of Group A patients and in 8.6%
      of Group B patients. In Group C, median stent patency was 16.3 mo, and stent
      exchange was carried out in 70.6% of cases because of acute cholangitis or
      obstructive jaundice. Although a high incidence of acute cholangitis occurred,
      there was no biliary-related mortality. CONCLUSION: Plastic stent exchange at 12
      mo intervals is considered a safe procedure for patients with
      choledocholithiasis. Long-term biliary stenting increases biliary complications,
      but it can be an acceptable option for select patients who are medically unfit
      for further invasive procedures.

PMID- 29375742
TI  - Bacterial presence on flexible endoscopes vs time since disinfection.
AB  - AIM: To correlate the length of endoscope hang time and number of bacteria
      cultured prior to use. METHODS: Prospectively, we cultured specimens from 19
      gastroscopes, 24 colonoscopes and 5 side viewing duodenoscopes during the period
      of 2011 to 2015. A total of 164 results had complete data denoting date of
      cleansing, number of days stored and culture results. All scopes underwent
      initial cleaning in the endoscopy suite utilizing tap water, and then manually
      cleaned and flushed. High level disinfection was achieved with a Medivator(c) DSD
      (Medivator Inc., United States) automated endoscope reprocessor following
      manufacturer instructions, with Glutacide(r) (Pharmax Limited, Canada), a 2%
      glutaraldehyde solution. After disinfection, all scopes were stored in dust free,
      unfiltered commercial cabinets for up to 7 d. Prior to use, all scopes were
      sampled and plated on sheep blood agar for 48 h; the colony count was obtained
      from each plate. The length of endoscope hang time and bacterial load was
      analyzed utilizing unpaired t-tests. The overall percentage of positive and
      negative cultures for each type of endoscope was also calculated. RESULTS: All
      culture results were within the acceptable range (less than 200 cfu/mL). One
      colonoscope cultured 80 cfu/mL after hanging for 1 d, which was the highest
      count. ERCP scopes cultured at most 10 cfu, this occurred after 2 and 7 d, and
      gastroscopes cultured 50 cfu/mL at most, at 1 d. Most cultures were negative for
      growth, irrespective of the length of hang time. Furthermore, all scopes, with
      the exception of one colonoscope which had two positive cultures (each of 10
      cfu/mL), had at most one positive culture. There was no significant difference in
      the number of bacteria cultured after 1 d compared to 7 d when all scopes were
      combined (day 2: P = 0.515; day 3: P = identical; day 4: P = 0.071; day 5: P =
      0.470; day 6: P = 0.584; day 7: P = 0.575). There was also no significant
      difference in the number of bacteria cultured after 1 day compared to 7 d for
      gastroscopes (day 2: P = 0.895; day 3: P = identical; day 4: P = identical; day
      5: P = 0.893; day 6: P = identical; day 7: P = 0.756), colonoscopes (day 2: P =
      0.489; day 4: P = 0.493; day 5: P = 0.324; day 6: P = 0.526; day 7: P =
      identical), or ERCP scopes (day 2: P = identical; day 7: P = 0.685). CONCLUSION:
      There is no correlation between hang time and bacterial load. Endoscopes do not
      need to be reprocessed if reused within a period of 7 d.

PMID- 29375744
TI  - Advance in plasma SEPT9 gene methylation assay for colorectal cancer early
      detection.
AB  - This review article summarizes the research advances of the plasma-based SEPT9
      gene methylation assay for the clinical detection of colorectal cancer and its
      limitations. Colorectal cancer is a common malignancy with a poor prognosis and a
      high mortality, for which early detection and diagnosis are particularly crucial
      for the high-risk groups. Increasing evidence supported that SEPT9 gene
      methylation is associated with the pathogenesis of colorectal cancer and that
      detecting the level of methylation of SEPT9 in the peripheral blood can be used
      for screening of colorectal cancer in susceptible populations. In recent years,
      the data obtained in clinical studies demonstrated that the SEPT9 gene
      methylation assay has a good diagnostic performance with regard to both
      sensitivity and specificity with the advantage of better acceptability,
      convenience and compliance with serological testing compared with fecal occult
      blood tests and carcinoembryonic antigen for colorectal cancer (CRC).
      Furthermore, the combination of multiple methods or markers has become a growing
      trend for CRC detection and screening. Nevertheless, the clinical availability of
      the methylated SEPT9 assay is still limited because of the large degree of sample
      heterogeneity caused by demographic characteristics, pathological features,
      comorbidities and/or technique selection. Another factor is the cost
      effectiveness of colorectal cancer screening strategies that hinders its large
      scale application. In addition, improvements in its accuracy in detecting
      adenomas and premalignant polyps are required.

PMID- 29375745
TI  - Vitamin D in esophageal cancer: Is there a role for chemoprevention?
AB  - Vitamin D has emerged as a promising anti-cancer agent due to its diverse
      biological effects on tumor differentiation, apoptosis and suppression of
      cellular proliferation. Current evidence suggests a protective role of vitamin D
      in colon cancer. The effect of vitamin D on esophageal cancer remains
      controversial. Multiple studies investigated the association between vitamin D
      and esophageal cancer, employing different modes of assessment of vitamin D
      status such as serum 25-hydroxyvitamin D levels, vitamin D dietary intake or
      exposure to ultraviolet B (UVB) radiation. Genetic variations of the vitamin D
      receptor (VDR) gene and VDR expression in esophageal specimens have also been
      investigated. Ecological studies evaluating exposure to UVB radiation yielded an
      inverse correlation with esophageal cancer. When vitamin D dietary intake was
      assessed, direct association with esophageal cancer was observed. However,
      circulating 25-hydroxyvitamin D concentrations showed inconsistent results. In
      this review article, we present a detailed summary of the current data on the
      effects of vitamin D on various histological subtypes of esophageal cancer and
      their precursor lesions. Well-powered prospective studies with accurate
      measurement of vitamin D status are needed before chemoprevention with vitamin D
      is recommended, as current evidence does not support a chemopreventive role of
      vitamin D against esophageal cancer. Future studies looking at the incidence of
      esophageal cancer in patients with pre-cancerous lesions (Barrett's esophagus and
      squamous cell dysplasia) receiving vitamin D supplementation are needed.

PMID- 29375746
TI  - Impact of duration of adjuvant chemotherapy in radically resected patients with
      T4bN1-3M0/TxN3bM0 gastric cancer.
AB  - AIM: To provide evidence regarding the postoperative treatment of patients with
      T4bN1-3M0/TxN3bM0 gastric cancer, for which guidelines have not been established.
      METHODS: Patients who had undergone curative resection between 1996 and 2014 with
      a pathological stage of T4bN1-3M0/TxN3bM0 for gastric cancer were retrospectively
      analyzed; staging was based on the 7th edition of the American Joint Committee on
      Cancer staging system. The clinicopathological characteristics, administration of
      adjuvant chemotherapy, and patterns of recurrence were studied. Univariate and
      multivariate analyses of prognostic factors were conducted. The chemotherapeutic
      agents mainly included fluorouropyrimidine, platinum and taxanes, used as
      monotherapy, doublet, or triplet regimens. Patterns of first recurrence were
      categorized as locoregional recurrence, peritoneal dissemination, or distant
      metastasis. RESULTS: The 5-year overall survival (OS) of the whole group (n =
      176) was 16.8%, and the median OS was 25.7 mo (95%CI: 20.9-30.5). Lymphovascular
      invasion and a node positive rate (NPR) >= 0.8 were associated with a poor
      prognosis (P = 0.01 and P = 0.048, respectively). One hundred forty-seven (83.5%)
      of the 176 patients eventually experienced recurrence; the most common pattern of
      the first recurrence was distant metastasis. The prognosis was best for patients
      with locoregional recurrence and worst for those with peritoneal dissemination.
      Twelve (6.8%) of the 176 patients did not receive adjuvant chemotherapy, while
      164 (93.2%) patients received adjuvant chemotherapy. Combined chemotherapy,
      including doublet and triplet regimens, was associated with a better prognosis
      than monotherapy, with no significant difference in 5-year OS (17.5% vs 0%, P =
      0.613). The triplet regimen showed no significant survival benefit compared with
      the doublet regimen for 5-year OS (18.5% vs 17.4%, P = 0.661). Thirty-nine
      (22.1%) patients received adjuvant chemotherapy for longer than six months; the
      median OS in patients who received adjuvant chemotherapy for longer than six
      months was 40.2 mo (95%CI: 30.6-48.2), significantly longer than the 21.6 mo
      (95%CI: 19.1-24.0) in patients who received adjuvant chemotherapy for less than
      six months (P = 0.001). CONCLUSION: Patients with T4bN1-3M0/TxN3bM0 gastric
      cancer showed a poor prognosis and a high risk of distant metastasis. Adjuvant
      chemotherapy for longer than six months improved outcomes for them.

PMID- 29375743
TI  - Inflammation-associated microsatellite alterations: Mechanisms and significance
      in the prognosis of patients with colorectal cancer.
AB  - Microsatellite alterations within genomic DNA frameshift as a result of defective
      DNA mismatch repair (MMR). About 15% of sporadic colorectal cancers (CRCs)
      manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono- and di
      nucleotide frameshifts to classify it as microsatellite instability-high (MSI-H)
      and hypermutated, and due to frameshifts at coding microsatellites generating neo
      antigens, produce a robust protective immune response that can be enhanced with
      immune checkpoint blockade. More commonly, approximately 50% of sporadic non-MSI
      H CRCs demonstrate frameshifts at di- and tetra-nucleotide microsatellites to
      classify it as MSI-low/elevated microsatellite alterations at selected
      tetranucleotide repeats (EMAST) as a result of functional somatic inactivation of
      the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for
      MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike
      MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These
      inflammatory-associated microsatellite alterations are a consequence of the local
      tumor microenvironment, and in theory, if the microenvironment is manipulated to
      lower inflammation, the microsatellite alterations and MSH3 dysfunction should be
      corrected. Here we describe the mechanisms and significance of inflammatory
      associated microsatellite alterations, and propose three areas to deeply explore
      the consequences and prevention of inflammation's effect upon the DNA MMR system.

PMID- 29375747
TI  - Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5
      fluorouracil infusion in locally advanced rectal cancer: A phase II study.
AB  - AIM: To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated
      accelerated radiotherapy (HART) and concurrent chemotherapy in patients with
      locally advanced infraperitoneal rectal cancer. METHODS: A total of 30 patients
      with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of
      rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid
      radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m2). All patients
      were operated 4-8 wk after neoadjuvant concomitant therapy. RESULTS: In the early
      phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2
      patients had grade III-IV hematologic toxicity, and 1 patient had grade V
      toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had
      radiotherapy-related late side effects, i.e., grade IV tenesmus. Complete
      pathological response was achieved in 6 patients (21%), while near-complete
      pathological response was obtained in 9 (31%). After a median follow-up period of
      60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis
      occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and
      corresponding overall survival rates were 70% and 53.1%, respectively.
      CONCLUSION: Although it has excellent local control and complete pathological
      response rates, neoadjuvant HART concurrent chemotherapy appears to not be a
      feasible treatment regimen in locally advanced rectal cancer, having high
      perioperative complication and intolerable side effects. Effects of reduced 5
      fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity
      may be examined in further studies.

PMID- 29375748
TI  - Comparison between laparoscopic and open surgery for large gastrointestinal
      stromal tumors: A meta-analysis.
AB  - AIM: To investigate whether laparoscopic surgery is as safe and feasible as open
      resection for patients with larger gastrointestinal stromal tumors (GISTs) (>= 5
      cm). METHODS: A systematic search of PubMed, EMBASE, Web of Science and the
      Cochrane Library database was performed. Relevant studies of laparoscopic and
      open surgery for GISTs of > 5 cm published before December 2016 were identified
      from these databases. The quality of the studies was assessed by the Newcastle
      Ottawa Quality Assessment Scale. The tumor size, operation time, blood loss,
      postoperative hospital stay, complication rate, and disease-free survival rate
      were assessed. The software Stata (version 12.0) was used for the meta-analysis.
      RESULTS: Five clinical trials comprising 209 patients with GISTs of similar
      larger sizes were evaluated. The pooled analysis of 100 patients in the
      laparoscopic resection group and 109 patients in the open resection group
      demonstrated that laparoscopic surgery was significantly associated with a
      shorter postoperative hospital stay (P < 0.001) and less blood loss (P = 0.002).
      Moreover, there were no statistically significant differences in the operation
      time (P = 0.38), postoperative complication rate (P = 0.88), or disease-free
      survival rate (P = 0.20) between two groups. CONCLUSION: Our findings revealed
      that for patients with large GISTs of comparable sizes, laparoscopic surgery did
      not significantly influence the operation factors or clinical outcomes compared
      with open surgery. This suggests that laparoscopic resection is as acceptable as
      open surgery for treatment of large gastric GISTs.

PMID- 29375749
TI  - Leptomeningeal metastases originated from esophagogastric junction/gastric
      cancer: A brief report of two cases.
AB  - Leptomeningeal carcinomatosis is a very rare manifestation in patients diagnosed
      with esophagogastric junction and gastric cancer. Its prognosis is ominous and
      therapy outcomes are disappointing. Herein, we present two patients; one
      initially diagnosed with gastric cancer and leptomeningeal carcinomatosis but no
      other evidence of metastatic disease and the other one initially diagnosed with
      esophagogastric junction cancer, who recurred solitary with leptomeningeal
      seedings several years after the initial diagnosis and treatment. Furthermore, a
      thorough and short review of the literature is carried out.

PMID- 29375750
TI  - Structure-Activity Relationship Studies with Tetrahydroquinoline Analogs as EPAC
      Inhibitors.
AB  - EPAC proteins are therapeutic targets for the potential treatment of cardiac
      hypertrophy and cancer metastasis. Several laboratories use a tetrahydroquinoline
      analog, CE3F4, to dissect the role of EPAC1 in various disease states. Here, we
      report SAR studies with tetrahydroquinoline analogs that explore various
      functional groups. The most potent EPAC inhibitor 12a exists as a mixture of
      inseparable E (major) and Z (minor) rotamers. The rotation about the N-formyl
      group indeed impacts the activity against EPAC.

PMID- 29375751
TI  - Roadmap on optical sensors.
AB  - Sensors are devices or systems able to detect, measure and convert magnitudes
      from any domain to an electrical one. Using light as a probe for optical sensing
      is one of the most efficient approaches for this purpose. The history of optical
      sensing using some methods based on absorbance, emissive and florescence
      properties date back to the 16th century. The field of optical sensors evolved
      during the following centuries, but it did not achieve maturity until the
      demonstration of the first laser in 1960. The unique properties of laser light
      become particularly important in the case of laser-based sensors, whose operation
      is entirely based upon the direct detection of laser light itself, without
      relying on any additional mediating device. However, compared with freely
      propagating light beams, artificially engineered optical fields are in increasing
      demand for probing samples with very small sizes and/or weak light-matter
      interaction. Optical fiber sensors constitute a subarea of optical sensors in
      which fiber technologies are employed. Different types of specialty and photonic
      crystal fibers provide improved performance and novel sensing concepts. Actually,
      structurization with wavelength or subwavelength feature size appears as the most
      efficient way to enhance sensor sensitivity and its detection limit. This leads
      to the area of micro- and nano-engineered optical sensors. It is expected that
      the combination of better fabrication techniques and new physical effects may
      open new and fascinating opportunities in this area. This roadmap on optical
      sensors addresses different technologies and application areas of the field.
      Fourteen contributions authored by experts from both industry and academia
      provide insights into the current state-of-the-art and the challenges faced by
      researchers currently. Two sections of this paper provide an overview of laser
      based and frequency comb-based sensors. Three sections address the area of
      optical fiber sensors, encompassing both conventional, specialty and photonic
      crystal fibers. Several other sections are dedicated to micro- and nano
      engineered sensors, including whispering-gallery mode and plasmonic sensors. The
      uses of optical sensors in chemical, biological and biomedical areas are
      described in other sections. Different approaches required to satisfy
      applications at visible, infrared and THz spectral regions are also discussed.
      Advances in science and technology required to meet challenges faced in each of
      these areas are addressed, together with suggestions on how the field could
      evolve in the near future.

PMID- 29375752
TI  - Stacking Chairs: Local Sense and Global Nonsense.
AB  - We report a confusing stimulus which demonstrates the power of local
      interpretation of three-dimensional structure to disrupt a coherent global
      perception.

PMID- 29375753
TI  - Cortical Double-Opponent Cells in Color Perception: Perceptual Scaling and
      Chromatic Visual Evoked Potentials.
AB  - In the early visual cortex V1, there are currently only two known neural
      substrates for color perception: single-opponent and double-opponent cells. Our
      aim was to explore the relative contributions of these neurons to color
      perception. We measured the perceptual scaling of color saturation for
      equiluminant color checkerboard patterns (designed to stimulate double-opponent
      neurons preferentially) and uniformly colored squares (designed to stimulate only
      single-opponent neurons) at several cone contrasts. The spatially integrative
      responses of single-opponent neurons would produce the same response magnitude
      for checkerboards as for uniform squares of the same space-averaged cone
      contrast. However, perceived saturation of color checkerboards was higher than
      for the corresponding squares. The perceptual results therefore imply that double
      opponent cells are involved in color perception of patterns. We also measured the
      chromatic visual evoked potential (cVEP) produced by the same stimuli;
      checkerboard cVEPs were much larger than those for corresponding squares,
      implying that double-opponent cells also contribute to the cVEP response. The
      total Fourier power of the cVEP grew sublinearly with cone contrast. However, the
      6-Hz Fourier component's power grew linearly with contrast-like saturation
      perception. This may also indicate that cortical coding of color depends on
      response dynamics.

PMID- 29375754
TI  - Effect of Grouping, Segmentation, and Vestibular Stimulation on the Autokinetic
      Effect.
AB  - We report some new observations on what could be regarded as the world's simplest
      visual illusion-the autokinetic effect. When a single dim spot of light is viewed
      in a completely dark room, it moves vividly in random directions. During steady
      fixation, perhaps subtle eye movements cause the image to move and a failure to
      correct for this using eye movement command signals leads to motion perception.
      This is especially true because eye muscle fatigue can lead to miscalibration.
      However, if two dots are shown, they often move independently in different
      directions, which negate the eye movement theory. In addition, two lines defining
      a single cross sometimes uncouple and slide past each other and the fragments
      composing a hidden object move independently until they click in place and the
      whole object is perceived-implying that the illusion occurs relatively late in
      visual processing. Finally, the effect is modulated by vestibular stimulation;
      anchoring your sense of self may be a prerequisite for binding features into
      coherent objects.

PMID- 29375755
TI  - Transient Signals and Inattentional Blindness in a Multi-object Tracking Task.
AB  - Inattentional blindness is a failure to notice an unexpected event when attention
      is directed elsewhere. The current study examined participants' awareness of an
      unexpected object that maintained luminance contrast, switched the luminance
      once, or repetitively flashed. One hundred twenty participants performed a
      dynamic tracking task on a computer monitor for which they were instructed to
      count the number of movement deflections of an attended set of objects while
      ignoring other objects. On the critical trial, an unexpected cross that did not
      change its luminance (control condition), switched its luminance once (switch
      condition), or repetitively flashed (flash condition) traveled across the
      stimulus display. Participants noticed the unexpected cross more frequently when
      the luminance feature matched their attention set than when it did not match.
      Unexpectedly, however, a proportion of the participants who noticed the cross in
      the switch and flash conditions were statistically comparable. The results
      suggest that an unexpected object with even a single luminance change can break
      inattentional blindness in a multi-object tracking task.

PMID- 29375756
TI  - The use of human dental pulp stem cells for in vivo bone tissue engineering: A
      systematic review.
AB  - Dental pulp represents a promising and easily accessible source of mesenchymal
      stem cells for clinical applications. Many studies have investigated the use of
      human dental pulp stem cells and stem cells isolated from the dental pulp of
      human exfoliated deciduous teeth for bone tissue engineering in vivo. However,
      the type of scaffold used to support the proliferation and differentiation of
      dental stem cells, the animal model, the type of bone defect created, and the
      methods for evaluation of results were extremely heterogeneous among these
      studies conducted. With this issue in mind, the main objective of this study is
      to present and summarize, through a systematic review of the literature, in vivo
      studies in which the efficacy of human dental pulp stem cells and stem cells from
      human exfoliated deciduous teeth (SHED) for bone regeneration was evaluated. The
      article search was conducted in PubMed/MEDLINE and Web of Science databases.
      Original research articles assessing potential of human dental pulp stem cells
      and SHED for in vivo bone tissue engineering, published from 1984 to November
      2017, were selected and evaluated in this review according to the following
      eligibility criteria: published in English, assessing dental stem cells of human
      origin and evaluating in vivo bone tissue formation in animal models or in
      humans. From the initial 1576 potentially relevant articles identified, 128 were
      excluded due to the fact that they were duplicates and 1392 were considered
      ineligible as they did not meet the inclusion criteria. As a result, 56 articles
      remained and were fully analyzed in this systematic review. The results obtained
      in this systematic review open new avenues to perform bone tissue engineering for
      patients with bone defects and emphasize the importance of using human dental
      pulp stem cells and SHED to repair actual bone defects in an appropriate animal
      model.

PMID- 29375758
TI  - How to deal with ground truthing affected by human-induced habitat change?:
      Identifying high-quality habitats for the Critically Endangered Red Siskin.
AB  - Species distribution models (SDM) can be valuable for identifying key habitats
      for conservation management of threatened taxa, but anthropogenic habitat change
      can undermine SDM accuracy. We used data for the Red Siskin (Spinus cucullatus),
      a critically endangered bird and ground truthing to examine anthropogenic habitat
      change as a source of SDM inaccuracy. We aimed to estimate: (1) the Red Siskin's
      historic distribution in Venezuela; (2) the portion of this historic distribution
      lost to vegetation degradation; and (3) the location of key habitats or areas
      with both, a high probability of historic occurrence and a low probability of
      vegetation degradation. We ground-truthed 191 locations and used expert opinion
      as well as landscape characteristics to classify species' habitat suitability as
      excellent, good, acceptable, or poor. We fit a Random Forest model (RF) and
      Enhanced Vegetation Index (EVI) time series to evaluate the accuracy and
      precision of the expert categorization of habitat suitability. We estimated the
      probability of historic occurrence by fitting a MaxLike model using 88 presence
      records (1960-2013) and data on forest cover and aridity index. Of the entire
      study area, 23% (20,696 km2) had a historic probability of Red Siskin occurrence
      over 0.743. Furthermore, 85% of ground-truthed locations had substantial
      reductions in mean EVI, resulting in key habitats totaling just 976 km2, in small
      blocks in the western and central regions. Decline in Area of Occupancy over 15
      years was between 40% and 95%, corresponding to an extinction risk category
      between Vulnerable and Critically Endangered. Relating key habitats with other
      landscape features revealed significant risks and opportunities for proposed
      conservation interventions, including the fact that ongoing vegetation
      degradation could limit the establishment of reintroduced populations in eastern
      areas, while the conservation of remaining key habitats on private lands could be
      improved with biodiversity-friendly agri- and silviculture programs.

PMID- 29375757
TI  - Parasite spillover: indirect effects of invasive Burmese pythons.
AB  - Identification of the origin of parasites of nonindigenous species (NIS) can be
      complex. NIS may introduce parasites from their native range and acquire
      parasites from within their invaded range. Determination of whether parasites are
      non-native or native can be complicated when parasite genera occur within both
      the NIS' native range and its introduced range. We explored potential for
      spillover and spillback of lung parasites infecting Burmese pythons (Python
      bivittatus) in their invasive range (Florida). We collected 498 indigenous snakes
      of 26 species and 805 Burmese pythons during 2004-2016 and examined them for lung
      parasites. We used morphology to identify three genera of pentastome parasites,
      Raillietiella, a cosmopolitan form, and Porocephalus and Kiricephalus, both New
      World forms. We sequenced these parasites at one mitochondrial and one nuclear
      locus and showed that each genus is represented by a single species, R.
      orientalis, P. crotali, and K. coarctatus. Pythons are host to R. orientalis and
      P. crotali, but not K. coarctatus; native snakes are host to all three species.
      Sequence data show that pythons introduced R. orientalis to North America, where
      this parasite now infects native snakes. Additionally, our data suggest that
      pythons are competent hosts to P. crotali, a widespread parasite native to North
      and South America that was previously hypothesized to infect only viperid snakes.
      Our results indicate invasive Burmese pythons have affected parasite-host
      dynamics of native snakes in ways that are consistent with parasite spillover and
      demonstrate the potential for indirect effects during invasions. Additionally, we
      show that pythons have acquired a parasite native to their introduced range,
      which is the initial condition necessary for parasite spillback.

PMID- 29375759
TI  - Improving the use of environmental diversity as a surrogate for species
      representation.
AB  - The continuous p-median approach to environmental diversity (ED) is a reliable
      way to identify sites that efficiently represent species. A recently developed
      maximum dispersion (maxdisp) approach to ED is computationally simpler, does not
      require the user to reduce environmental space to two dimensions, and performed
      better than continuous p-median for datasets of South African animals. We tested
      whether maxdisp performs as well as continuous p-median for 12 datasets that
      included plants and other continents, and whether particular types of
      environmental variables produced consistently better models of ED. We selected 12
      species inventories and atlases to span a broad range of taxa (plants, birds,
      mammals, reptiles, and amphibians), spatial extents, and resolutions. For each
      dataset, we used continuous p-median ED and maxdisp ED in combination with five
      sets of environmental variables (five combinations of temperature, precipitation,
      insolation, NDVI, and topographic variables) to select environmentally diverse
      sites. We used the species accumulation index (SAI) to evaluate the efficiency of
      ED in representing species for each approach and set of environmental variables.
      Maxdisp ED represented species better than continuous p-median ED in five of 12
      biodiversity datasets, and about the same for the other seven biodiversity
      datasets. Efficiency of ED also varied with type of variables used to define
      environmental space, but no particular combination of variables consistently
      performed best. We conclude that maxdisp ED performs at least as well as
      continuous p-median ED, and has the advantage of faster and simpler computation.
      Surprisingly, using all 38 environmental variables was not consistently better
      than using subsets of variables, nor did any subset emerge as consistently best
      or worst; further work is needed to identify the best variables to define
      environmental space. Results can help ecologists and conservationists select
      sites for species representation and assist in conservation planning.

PMID- 29375760
TI  - Evolutionary history of Daphnia drives divergence in grazing selectivity and
      alters temporal community dynamics of producers.
AB  - Consumers with different seasonal life histories encounter different communities
      of producers during specific seasonal phases. If consumers evolve to prefer the
      producers that they encounter, then consumers may reciprocally influence the
      temporal composition of producer communities. Here, we study the keystone
      consumer Daphnia ambigua, whose seasonal life history has diverged due to
      intraspecific predator divergence across lakes of New England. We ask whether
      grazing preferences of Daphnia have diverged also and test whether any grazing
      differences influence temporal composition patterns of producers. We reared
      clonal populations of Daphnia from natural populations representing the two
      diverged life history types for multiple generations. We conducted short-term (24
      hr) and long-term (27 days) grazing experiments in equal polycultures consisting
      of three diatom and two green algae species, treated with no consumer, Daphnia
      from lakes with anadromous alewife, or from lakes with landlocked alewife. After
      24 hr, life history and grazing preference divergence in Daphnia ambigua drove
      significant differences in producer composition. However, those differences
      disappeared at the end of the 27-day experiment. Our results illustrate that,
      despite potentially more complex long-term dynamics, a multitrophic cascade of
      evolutionary divergence from a predator can influence temporal community dynamics
      at the producer level.

PMID- 29375761
TI  - Taking a trip to the shelf: Behavioral decisions are mediated by the proximity to
      foraging habitats in the black-legged kittiwake.
AB  - For marine top predators like seabirds, the oceans represent a multitude of
      habitats regarding oceanographic conditions and food availability. Worldwide,
      these marine habitats are being altered by changes in climate and increased
      anthropogenic impact. This is causing a growing concern on how seabird
      populations might adapt to these changes. Understanding how seabird populations
      respond to fluctuating environmental conditions and to what extent behavioral
      flexibility can buffer variations in food availability can help predict how
      seabirds may cope with changes in the marine environment. Such knowledge is
      important to implement proper long-term conservation measures intended to protect
      marine predators. We explored behavioral flexibility in choice of foraging
      habitat of chick-rearing black-legged kittiwakes Rissa tridactyla during multiple
      years. By comparing foraging behavior of individuals from two colonies with large
      differences in oceanographic conditions and distances to predictable feeding
      areas at the Norwegian shelf break, we investigated how foraging decisions are
      related to intrinsic and extrinsic factors. We found that proximity to the shelf
      break determined which factors drove the decision to forage there. At the colony
      near the shelf break, time of departure from the colony and wind speed were most
      important in driving the choice of habitat. At the colony farther from the shelf
      break, the decision to forage there was driven by adult body condition. Birds
      furthermore adjusted foraging behavior metrics according to time of the day,
      weather conditions, body condition, and the age of the chicks. The study shows
      that kittiwakes have high degree of flexibility in their behavioral response to a
      variable marine environment, which might help them buffer changes in prey
      distribution around the colonies. The flexibility is, however, dependent on the
      availability of foraging habitats near the colony.

PMID- 29375762
TI  - Effects of temperature, soil substrate, and microbial community on carbon
      mineralization across three climatically contrasting forest sites.
AB  - How biotic and abiotic factors influence soil carbon (C) mineralization rate (RS)
      has recently emerged as one of the focal interests in ecological studies. To
      determine the relative effects of temperature, soil substrate and microbial
      community on Rs, we conducted a laboratory experiment involving reciprocal
      microbial inoculations of three zonal forest soils, and measured RS over a 61-day
      period at three temperatures (5, 15, and 25 degrees C). Results show that both Rs
      and the cumulative emission of C (Rcum), normalized to per unit soil organic C
      (SOC), were significantly affected by incubation temperature, soil substrate,
      microbial inoculum treatment, and their interactions (p < .05). Overall, the
      incubation temperature had the strongest effect on the RS; at given temperatures,
      soil substrate, microbial inoculum treatment, and their interaction all
      significantly affected both Rs (p < .001) and Rcum (p <= .01), but the effect of
      soil substrate was much stronger than others. There was no consistent pattern of
      thermal adaptation in microbial decomposition of SOC in the reciprocal
      inoculations. Moreover, when different sources of microbial inocula were
      introduced to the same soil substrate, the microbial community structure
      converged with incubation without altering the overall soil enzyme activities;
      when different types of soil substrate were inoculated with the same sources of
      microbial inocula, both the microbial community structure and soil enzyme
      activities diverged. Overall, temperature plays a predominant role in affecting
      Rs and Rcum, while soil substrate determines the mineralizable SOC under given
      conditions. The role of microbial community in driving SOC mineralization is
      weaker than that of climate and soil substrate, because soil microbial community
      is both affected, and adapts to, climatic factors and soil matrix.

PMID- 29375763
TI  - Herbivory and pollen limitation at the upper elevational range limit of two
      forest understory plants of eastern North America.
AB  - Studies of species' range limits focus most often on abiotic factors, although
      the strength of biotic interactions might also vary along environmental gradients
      and have strong demographic effects. For example, pollinator abundance might
      decrease at range limits due to harsh environmental conditions, and reduced plant
      density can reduce attractiveness to pollinators and increase or decrease
      herbivory. We tested for variation in the strength of pollen limitation and
      herbivory by ungulates along a gradient leading to the upper elevational range
      limits of Trillium erectum (Melanthiaceae) and Erythronium americanum (Liliaceae)
      in Mont Megantic National Park, Quebec, Canada. In T. erectum, pollen limitation
      was higher at the range limit, but seed set decreased only slightly with
      elevation and only in one of two years. In contrast, herbivory of T. erectum
      increased from <10% at low elevations to >60% at the upper elevational range
      limit. In E. americanum, we found no evidence of pollen limitation despite a
      significant decrease in seed set with elevation, and herbivory was low across the
      entire gradient. Overall, our results demonstrate the potential for relatively
      strong negative interactions (herbivory) and weak positive interactions
      (pollination) at plant range edges, although this was clearly species specific.
      To the extent that these interactions have important demographic consequences
      highly likely for herbivory on Trillium, based on previous studies-such
      interactions might play a role in determining plant species' range limits along
      putatively climatic gradients.

PMID- 29375764
TI  - Is Didymosphenia geminata an introduced species in New Zealand? Evidence from
      trends in water chemistry, and chloroplast DNA.
AB  - Defining the geographic origins of free-living aquatic microorganisms can be
      problematic because many such organisms have ubiquitous distributions, and
      proving absence from a region is practically impossible. Geographic origins
      become important if microorganisms have invasive characteristics. The freshwater
      diatom Didymosphenia geminata is a potentially ubiquitous microorganism for which
      the recent global expansion of nuisance proliferations has been attributed to
      environmental change. The changes may include declines in dissolved reactive
      phosphorus (DRP) to low levels (e.g., <2 mg/m3) and increases in dissolved
      inorganic nitrogen (DIN) to >10 mg/m3 because both these nutrient conditions are
      associated with nuisance proliferations of D. geminata. Proliferations of D.
      geminata have been observed in South Island, New Zealand, since 2004. We aimed to
      address the ubiquity hypothesis for D. geminata in New Zealand using historical
      river water nutrient data and new molecular analyses. We used 15 years of data at
      77 river sites to assess whether trends in DRP or DIN prior to the spread of D.
      geminata were consistent with a transition from a rare, undetected, species to a
      nuisance species. We used new sequences of chloroplast regions to examine the
      genetic similarity of D. geminata populations from New Zealand and six overseas
      locations. We found no evidence for declines in DRP concentrations since 1989
      that could explain the spread of proliferations since 2004. At some affected
      sites, lowest DRP occurred before 2004. Trends in DIN also did not indicate
      enhanced suitability for D. geminata. Lack of diversity in the chloroplast
      intergenic regions of New Zealand populations and populations from western North
      America is consistent with recent dispersal to New Zealand. Our analyses did not
      support the proposal that D. geminata was historically present in New Zealand
      rivers. These results provide further evidence countering proposals of general
      ubiquity in freshwater diatoms and indicate that, as assumed in 2004, D. geminata
      is a recent arrival in New Zealand.

PMID- 29375765
TI  - Prolonged dry periods between rainfall events shorten the growth period of the
      resurrection plant Reaumuria soongorica.
AB  - The resurrection plant Reaumuria soongorica is widespread across Asia, southern
      Europe, and North Africa and is considered to be a constructive keystone species
      in desert ecosystems, but the impacts of climate change on this species in desert
      ecosystems are unclear. Here, the morphological responses of R. soongorica to
      changes in rainfall quantity (30% reduction and 30% increase in rainfall
      quantity) and interval (50% longer drought interval between rainfall events) were
      tested. Stage-specific changes in growth were monitored by sampling at the
      beginning, middle, and end of the growing season. Reduced rainfall decreased the
      aboveground and total biomass, while additional precipitation generally advanced
      R. soongorica growth and biomass accumulation. An increased interval between
      rainfall events resulted in an increase in root biomass in the middle of the
      growing season, followed by a decrease toward the end. The response to the
      combination of increased rainfall quantity and interval was similar to the
      response to increased interval alone, suggesting that the effects of changes in
      rainfall patterns exert a greater influence than increased rainfall quantity.
      Thus, despite the short duration of this experiment, consequences of changes in
      rainfall regime on seedling growth were observed. In particular, a prolonged
      rainfall interval shortened the growth period, suggesting that climate change
      induced rainfall variability may have significant effects on the structure and
      functioning of desert ecosystems.

PMID- 29375766
TI  - Minimum area thresholds for rattlesnakes and colubrid snakes on islands in the
      Gulf of California, Mexico.
AB  - We expand a framework for estimating minimum area thresholds to elaborate
      biogeographic patterns between two groups of snakes (rattlesnakes and colubrid
      snakes) on islands in the western Gulf of California, Mexico. The minimum area
      thresholds for supporting single species versus coexistence of two or more
      species relate to hypotheses of the relative importance of energetic efficiency
      and competitive interactions within groups, respectively. We used ordinal
      logistic regression probability functions to estimate minimum area thresholds
      after evaluating the influence of island area, isolation, and age on rattlesnake
      and colubrid occupancy patterns across 83 islands. Minimum area thresholds for
      islands supporting one species were nearly identical for rattlesnakes and
      colubrids (~1.7 km2), suggesting that selective tradeoffs for distinctive life
      history traits between rattlesnakes and colubrids did not result in any clear
      advantage of one life history strategy over the other on islands. However, the
      minimum area threshold for supporting two or more species of rattlesnakes (37.1
      km2) was over five times greater than it was for supporting two or more species
      of colubrids (6.7 km2). The great differences between rattlesnakes and colubrids
      in minimum area required to support more than one species imply that for islands
      in the Gulf of California relative extinction risks are higher for coexistence of
      multiple species of rattlesnakes and that competition within and between species
      of rattlesnakes is likely much more intense than it is within and between species
      of colubrids.

PMID- 29375767
TI  - Ecobat: An online resource to facilitate transparent, evidence-based
      interpretation of bat activity data.
AB  - Acoustic surveys of bats are one of the techniques most commonly used by
      ecological practitioners. The results are used in Ecological Impact Assessments
      to assess the likely impacts of future developments on species that are widely
      protected in law, and to monitor developments' postconstruction. However, there
      is no standardized methodology for analyzing or interpreting these data, which
      can make the assessment of the ecological value of a site very subjective.
      Comparisons of sites and projects are therefore difficult for ecologists and
      decision-makers, for example, when trying to identify the best location for a new
      road based on relative bat activity levels along alternative routes. Here, we
      present a new web-based, data-driven tool, Ecobat, which addresses the need for a
      more robust way of interpreting ecological data. Ecobat offers users an easy,
      standardized, and objective method for analyzing bat activity data. It allows
      ecological practitioners to compare bat activity data at regional and national
      scales and to generate a numerical indicator of the relative importance of a
      night's worth of bat activity. The tool is free and open-source; because the
      underlying algorithms are already developed, it could easily be expanded to new
      geographical regions and species. Data donation is required to ensure the
      robustness of the analyses; we use a positive feedback mechanism to encourage
      ecological practitioners to share data by providing in return high quality,
      contextualized data analysis, and graphical visualizations for direct use in
      ecological reports.

PMID- 29375768
TI  - Infrastructure features outperform environmental variables explaining rabbit
      abundance around motorways.
AB  - Human disturbance is widespread across landscapes in the form of roads that alter
      wildlife populations. Knowing which road features are responsible for the species
      response and their relevance in comparison with environmental variables will
      provide useful information for effective conservation measures. We sampled
      relative abundance of European rabbits, a very widespread species, in motorway
      verges at regional scale, in an area with large variability in environmental and
      infrastructure conditions. Environmental variables included vegetation structure,
      plant productivity, distance to water sources, and altitude. Infrastructure
      characteristics were the type of vegetation in verges, verge width, traffic
      volume, and the presence of embankments. We performed a variance partitioning
      analysis to determine the relative importance of two sets of variables on rabbit
      abundance. Additionally, we identified the most important variables and their
      effects model averaging after model selection by AICc on hypothesis-based models.
      As a group, infrastructure features explained four times more variability in
      rabbit abundance than environmental variables, being the effects of the former
      critical in motorway stretches located in altered landscapes with no available
      habitat for rabbits, such as agricultural fields. Model selection and Akaike
      weights showed that verge width and traffic volume are the most important
      variables explaining rabbit abundance index, with positive and negative effects,
      respectively. In the light of these results, the response of species to the
      infrastructure can be modulated through the modification of motorway features,
      being some of them manageable in the design phase. The identification of such
      features leads to suggestions for improvement through low-cost corrective
      measures and conservation plans. As a general indication, keeping motorway verges
      less than 10 m wide will prevent high densities of rabbits and avoid the unwanted
      effects that rabbit populations can generate in some areas.

PMID- 29375769
TI  - Does wing reduction influence the relationship between altitude and insect body
      size? A case study using New Zealand's diverse stonefly fauna.
AB  - Researchers have long been intrigued by evolutionary processes that explain
      biological diversity. Numerous studies have reported strong associations between
      animal body size and altitude, but insect analyses have often yielded equivocal
      results. Here, we analyze a collection database of New Zealand's diverse endemic
      stonefly fauna (106 species across 21 genera) to test for relationships between
      altitude and plecopteran body size. This insect assemblage includes a variety of
      wing-reduced (26 spp) and fully winged (80 spp) taxa and covers a broad range of
      altitudes (0-2,000 m). We detected significant relationships between altitude and
      body size for wing-reduced, but not fully winged, stonefly taxa. These results
      suggest that, while the maintenance of flight apparatus might place a constraint
      on body size in some fully winged species, the loss of flight may free insects
      from this evolutionary constraint. We suggest that rapid switches in insect
      dispersal ability may facilitate rapid evolutionary shifts across a number of
      biological attributes and may explain the inconsistent results from previous
      macroecological analyses of insect assemblages.

PMID- 29375770
TI  - Indirect risk effects reduce feeding efficiency of ducks during spring.
AB  - Indirect risk effects of predators on prey behavior can have more of an impact on
      prey populations than direct consumptive effects. Predation risk can elicit more
      vigilance behavior in prey, reducing the amount of time available for other
      activities, such as foraging, which could potentially reduce foraging efficiency.
      Understanding the conditions associated with predation risk and the specific
      effects predation risk have on prey behavior is important because it has direct
      influences on the profitability of food items found under various conditions and
      states of the forager. The goals of this study were to assess how ducks perceived
      predation risk in various habitat types and how strongly perceived risk versus
      energetic demand affected foraging behavior. We manipulated food abundance in
      different wetland types in Illinois, USA to reduce confounding between food
      abundance and vegetation structure. We conducted focal-animal behavioral samples
      on five duck species in treatment and control plots and used generalized linear
      mixed-effects models to compare the effects of vegetation structure versus other
      factors on the intensity with which ducks fed and the duration of feeding stints.
      Mallards fed more intensively and, along with blue-winged teal, used longer
      feeding stints in open habitats, consistent with the hypothesis that limited
      visibility was perceived to have a greater predation risk than unlimited
      visibility. The species temporally nearest to nesting, wood ducks, were willing
      to take more risks for a greater food reward, consistent with an increase in a
      marginal value of energy as they approached nesting. Our results indicate that
      some duck species value energy differently based on the surrounding vegetation
      structure and density. Furthermore, increases in the marginal value of energy can
      be more influential than perceived risk in shaping foraging behavior patterns.
      Based on these findings, we conclude that the value of various food items is not
      solely determined by energy contained in the item but by conditions in which it
      is found and the state of the forager.

PMID- 29375772
TI  - Sexually dimorphic swallows have higher extinction risk.
AB  - The effect of sexual selection on extinction risk remains unclear. In theory,
      sexual selection can lead to both increase and decrease extinction probability
      depending on the ecology of the study system. Thus, combining different groups
      might obscure patterns that can be found in groups that share similar ecological
      features. Using phylogenetic comparative analysis, we studied sexual plumage
      dimorphism in relation to the perceived risk of extinction in hirundines
      (subfamily: Hirundininae), in which all species are socially monogamous aerial
      foragers. Among the 72 species studied, five species are facing a perceived
      threat of extinction. Species with sexually dimorphic plumage had a higher risk
      of extinction than did species with sexually monomorphic plumage. Likewise, when
      focusing solely on tail ornamentation, species that exhibit a sexual dimorphism
      in tail length had a higher risk of extinction than did other species. In
      Hirundininae, which are affected a great deal by severe weather, sexual selection
      and the resultant sexual dimorphism would increase extinction risk.

PMID- 29375771
TI  - General environmental heterogeneity as the explanation of sexuality? Comparative
      study shows that ancient asexual taxa are associated with both biotically and
      abiotically homogeneous environments.
AB  - Ecological theories of sexual reproduction assume that sexuality is advantageous
      in certain conditions, for example, in biotically or abiotically more
      heterogeneous environments. Such theories thus could be tested by comparative
      studies. However, the published results of these studies are rather unconvincing.
      Here, we present the results of a new comparative study based exclusively on the
      ancient asexual clades. The association with biotically or abiotically
      homogeneous environments in these asexual clades was compared with the same
      association in their sister, or closely related, sexual clades. Using the
      conservative definition of ancient asexuals (i.e., age >1 million years), we
      found eight pairs of taxa of sexual and asexual species, six differing in the
      heterogeneity of their inhabited environment on the basis of available data. The
      difference between the environmental type associated with the sexual and asexual
      species was then compared in an exact binomial test. The results showed that the
      majority of ancient asexual clades tend to be associated with biotically,
      abiotically, or both biotically and abiotically more homogeneous environments
      than their sexual controls. In the exploratory part of the study, we found that
      the ancient asexuals often have durable resting stages, enabling life in
      subjectively homogeneous environments, live in the absence of intense biotic
      interactions, and are very often sedentary, inhabiting benthos, and soil. The
      consequences of these findings for the ecological theories of sexual reproduction
      are discussed.

PMID- 29375773
TI  - Diving behavior in a free-living, semi-aquatic herbivore, the Eurasian beaver
      Castor fiber.
AB  - Semi-aquatic mammals have secondarily returned to the aquatic environment,
      although they spend a major part of their life operating in air. Moving both on
      land, as well as in, and under water is challenging because such species are
      considered to be imperfectly adapted to both environments. We deployed
      accelerometers combined with a depth sensor to study the diving behavior of 12
      free-living Eurasian beavers Castor fiber in southeast Norway between 2009 and
      2011 to examine the extent to which beavers conformed with mass-dependent dive
      capacities, expecting them to be poorer than wholly aquatic species. Dives were
      generally shallow (<1 m) and of short duration (<30 s), suggesting that the
      majority of dives were aerobic. Dive parameters such as maximum diving depth,
      dive duration, and bottom phase duration were related to the effort during
      different dive phases and the maximum depth reached. During the descent, mean
      vectorial dynamic body acceleration (VeDBA-a proxy for movement power) was
      highest near the surface, probably due to increased upthrust linked to fur- and
      lung-associated air. Inconsistently though, mean VeDBA underwater was highest
      during the ascent when this air would be expected to help drive the animals back
      to the surface. Higher movement costs during ascents may arise from transporting
      materials up, the air bubbling out of the fur, and/or the animals' exhaling
      during the bottom phase of the dive. In a manner similar to other homeotherms,
      beavers extended both dive and bottom phase durations with diving depth. Deeper
      dives tended to have a longer bottom phase, although its duration was shortened
      with increased VeDBA during the bottom phase. Water temperature did not affect
      diving behavior. Overall, the beavers' dive profile (depth, duration) was similar
      to other semi-aquatic freshwater divers. However, beavers dived for only 2.8% of
      their active time, presumably because they do not rely on diving for food
      acquisition.

PMID- 29375774
TI  - Genetic sex determination assays in 53 mammalian species: Literature analysis and
      guidelines for reporting standardization.
AB  - Erstwhile, sex was determined by observation, which is not always feasible.
      Nowadays, genetic methods are prevailing due to their accuracy, simplicity, low
      costs, and time-efficiency. However, there is no comprehensive review enabling
      overview and development of the field. The studies are heterogeneous, lacking a
      standardized reporting strategy. Therefore, our aim was to collect genetic sexing
      assays for mammals and assemble them in a catalogue with unified terminology.
      Publications were extracted from online databases using key words such as sexing
      and molecular. The collected data were supplemented with species and gene IDs and
      the type of sex-specific sequence variant (SSSV). We developed a catalogue and
      graphic presentation of diagnostic tests for molecular sex determination of
      mammals, based on 58 papers published from 2/1991 to 10/2016. The catalogue
      consists of five categories: species, genes, SSSVs, methods, and references.
      Based on the analysis of published literature, we propose minimal requirements
      for reporting, consisting of: species scientific name and ID, genetic sequence
      with name and ID, SSSV, methodology, genomic coordinates (e.g., restriction
      sites, SSSVs), amplification system, and description of detected amplicon and
      controls. The present study summarizes vast knowledge that has up to now been
      scattered across databases, representing the first step toward standardization
      regarding molecular sexing, enabling a better overview of existing tests and
      facilitating planned designs of novel tests. The project is ongoing; collecting
      additional publications, optimizing field development, and standardizing data
      presentation are needed.

PMID- 29375775
TI  - Complex effects of mammalian grazing on extramatrical mycelial biomass in the
      Scandes forest-tundra ecotone.
AB  - Mycorrhizal associations are widespread in high-latitude ecosystems and are
      potentially of great importance for global carbon dynamics. Although large
      herbivores play a key part in shaping subarctic plant communities, their impact
      on mycorrhizal dynamics is largely unknown. We measured extramatrical mycelial
      (EMM) biomass during one growing season in 16-year-old herbivore exclosures and
      unenclosed control plots (ambient), at three mountain birch forests and two shrub
      heath sites, in the Scandes forest-tundra ecotone. We also used high-throughput
      amplicon sequencing for taxonomic identification to investigate differences in
      fungal species composition. At the birch forest sites, EMM biomass was
      significantly higher in exclosures (1.36 +/- 0.43 g C/m2) than in ambient
      conditions (0.66 +/- 0.17 g C/m2) and was positively influenced by soil thawing
      degree-days. At the shrub heath sites, there was no significant effect on EMM
      biomass (exclosures: 0.72 +/- 0.09 g C/m2; ambient plots: 1.43 +/- 0.94).
      However, EMM biomass was negatively related to Betula nana abundance, which was
      greater in exclosures, suggesting that grazing affected EMM biomass positively.
      We found no significant treatment effects on fungal diversity but the most
      abundant ectomycorrhizal lineage/cortinarius, showed a near-significant positive
      effect of herbivore exclusion (p = .08), indicating that herbivory also affects
      fungal community composition. These results suggest that herbivory can influence
      fungal biomass in highly context-dependent ways in subarctic ecosystems.
      Considering the importance of root-associated fungi for ecosystem carbon balance,
      these findings could have far-reaching implications.

PMID- 29375776
TI  - Increased temperature disrupts chemical communication in some species but not
      others: The importance of local adaptation and distribution.
AB  - Environmental conditions experienced by a species during its evolutionary history
      may shape the signals it uses for communication. Consequently, rapid
      environmental changes may lead to less effective signals, which interfere with
      communication between individuals, altering life history traits such as predator
      detection and mate searching. Increased temperature can reduce the efficacy of
      scent marks released by male lizards, but the extent to which this negative
      effect is related to specific biological traits and evolutionary histories across
      species and populations have not been explored. We experimentally tested how
      increased temperature affects the efficacy of chemical signals of high- and low
      altitude populations of three lizard species that differ in their ecological
      requirements and altitudinal distributions. We tested the behavioral chemosensory
      responses of males from each species and population to male scent marks that had
      been incubated at one of two temperatures (cold 16 degrees C or hot 20 degrees
      C). In high-altitude populations of a mountain species (Iberolacerta monticola),
      the efficacy of chemical signals (i.e., latency time and number of tongue flicks)
      was lower after scent marks had been exposed to a hot temperature. The
      temperature that scent marks were incubated at did not affect the efficacy of
      chemical signals in a ubiquitous species (Podarcis muralis) or another mountain
      species (I. bonalli). Our results suggest that specific ecological traits arising
      through local adaptation to restricted distributions may be important in
      determining species vulnerability to climatic change.

PMID- 29375777
TI  - A stoichiometric perspective of the effect of herbivore dung on ecosystem
      functioning.
AB  - Ungulate herbivores play a prominent role in maintaining the tree-grass balance
      in African savannas. Their top-down role through selective feeding on either
      trees or grasses is well studied, but their bottom-up role through deposition of
      nutrients in dung and urine has been overlooked. Here, we propose a novel concept
      of savanna ecosystem functioning in which the balance between trees and grasses
      is maintained through stoichiometric differences in dung of herbivores that feed
      on them. We describe a framework in which N2-fixing trees and grasses, as well as
      ungulate browsing and grazing herbivores, occupy opposite positions in an
      interconnected cycle of processes. The framework makes the testable assumption
      that the differences in dung N:P ratio among browsers and grazers are large
      enough to influence competitive interactions between N2-fixing trees and grasses.
      Other key elements of our concept are supported with field data from a Kenyan
      savanna.

PMID- 29375778
TI  - Are there morphological and life-history traits under climate-dependent
      differential selection in S Tunesian Diplotaxis harra (Forssk.) Boiss.
      (Brassicaceae) populations?
AB  - Adaptation of morphological, physiological, or life-history traits of a plant
      species to heterogeneous habitats through the process of natural selection is a
      paramount process in evolutionary biology. We have used a population genomic
      approach to disentangle selection-based and demography-based variation in
      morphological and life-history traits in the crucifer Diplotaxis harra (Forssk.)
      Boiss. (Brassicaceae) encountered in populations along aridity gradients in S
      Tunisia. We have genotyped 182 individuals from 12 populations of the species
      ranging from coastal to semidesert habitats using amplified fragment length
      polymorphism (AFLP) fingerprinting and assessed a range of morphological and life
      history traits from their progeny cultivated under common-garden conditions.
      Application of three different statistical approaches for searching AFLP loci
      under selection allowed us to characterize candidate loci, for which their
      association with the traits assessed was tested for statistical significance and
      correlation with climate data. As a key result of this study, we find that only
      the shape of cauline leaves seems to be under differential selection along the
      aridity gradient in S Tunisian populations of Diplotaxis harra, while for all
      other traits studied neutral biogeographical and/or random factors could not be
      excluded as explanation for the variation observed. The counter-intuitive finding
      that plants from populations with more arid habitats produce broader leaves under
      optimal conditions of cultivation than those from more mesic habitats is
      interpreted as being ascribable to selection for a higher plasticity in this
      trait under more unpredictable semidesert conditions compared to the more
      predictable ones in coastal habitats.

PMID- 29375779
TI  - Genome-wide single-nucleotide polymorphism data reveal cryptic species within
      cryptic freshwater snail species-The case of the Ancylus fluviatilis species
      complex.
AB  - DNA barcoding utilizes short standardized DNA sequences to identify species and
      is increasingly used in biodiversity assessments. The technique has unveiled an
      unforeseeably high number of morphologically cryptic species. However, if
      speciation has occurred relatively recently and rapidly, the use of single gene
      markers, and especially the exclusive use of mitochondrial markers, will
      presumably fail in delimitating species. Therefore, the true number of biological
      species might be even higher. One mechanism that can result in rapid speciation
      is hybridization of different species in combination with polyploidization, that
      is, allopolyploid speciation. In this study, we analyzed the population genetic
      structure of the polyploid freshwater snail Ancylus fluviatilis, for which
      allopolyploidization was postulated as a speciation mechanism. DNA barcoding has
      already revealed four cryptic species within A. fluviatilis (i.e., A. fluviatilis
      s. str., Ancylus sp. A-C), but early allozyme data even hint at the presence of
      additional cryptic lineages in Central Europe. We combined COI sequencing with
      high-resolution genome-wide SNP data (ddRAD data) to analyze the genetic
      structure of A. fluviatilis populations in a Central German low mountain range
      (Sauerland). The ddRAD data results indicate the presence of three cryptic
      species within A. fluviatilis s. str. occurring in sympatry and even syntopy,
      whereas mitochondrial sequence data only support the existence of one species,
      with shared haplotypes between species. Our study hence points to the limitations
      of DNA barcoding when dealing with organismal groups where speciation is assumed
      to have occurred rapidly, for example, through the process of
      allopolyploidization. We therefore emphasize that single marker DNA barcoding can
      underestimate the true species diversity and argue in strong favor of using
      genome-wide data for species delimitation in such groups.

PMID- 29375780
TI  - The baubellum is more developmentally and evolutionarily labile than the baculum.
AB  - Understanding the evolutionary forces that influence sexual dimorphism is a
      fundamental goal in biology. Here, we focus on one particularly extreme example
      of sexual dimorphism. Many mammal species possess a bone in their penis called a
      baculum. The female equivalent of this bone is called the baubellum and occurs in
      the clitoris, which is developmentally homologous to the male penis. To
      understand the potential linkage between these two structures, we scored
      baculum/baubellum presence/absence across 163 species and analyzed their
      distribution in a phylogenetic framework. The majority of species (N = 134)
      shared the same state in males and females (both baculum and baubellum present or
      absent). However, the baubellum has experienced significantly more transitions,
      and more recent transitions, so that the remaining 29 species have a baculum but
      not a well-developed baubellum. Even in species where both bones are present, the
      baubellum shows more ontogenetic variability and harbors more morphological
      variation than the baculum. Our study demonstrates that the baculum and baubellum
      are generally correlated across mammals, but that the baubellum is more
      evolutionarily and developmentally labile than the baculum. The accumulation of
      more evolutionary transitions, especially losses in the baubellum, as well as
      noisier developmental patterns, suggests that the baubellum may be nonfunctional,
      and lost over time.

PMID- 29375781
TI  - Experimental stress during molt suggests the evolution of condition-dependent and
      condition-independent ornaments in the king penguin.
AB  - Sexual selection and social selection are two important theories proposed for
      explaining the evolution of colorful ornamental traits in animals. Understanding
      signal honesty requires studying how environmental and physiological factors
      during development influence the showy nature of sexual and social ornaments. We
      experimentally manipulated physiological stress and immunity status during the
      molt in adult king penguins (Aptenodytes patagonicus), and studied the
      consequences of our treatments on colourful ornaments (yellow-orange and UV beak
      spots and yellow-orange auricular feather patches) known to be used in sexual and
      social contexts in this species. Whereas some ornamental features showed strong
      condition-dependence (yellow auricular feather chroma, yellow and UV chroma of
      the beak), others were condition-independent and remained highly correlated
      before and after the molt (auricular patch size and beak UV hue). Our study
      provides a rare examination of the links between ornament determinism and
      selection processes in the wild. We highlight the coexistence of ornaments costly
      to produce that may be honest signals used in mate choice, and ornaments for
      which honesty may be enforced by social mediation or rely on genetic constraints.

PMID- 29375782
TI  - Pollinator-mediated selection on floral size and tube color in Linum pubescens:
      Can differential behavior and preference in different times of the day maintain
      dimorphism?
AB  - Diversity of flower traits is often proposed as the outcome of selection exerted
      by pollinators. Positive directional pollinator-mediated selection on floral size
      has been widely shown to reduce phenotypic variance. However, the underlying
      mechanism of maintaining within-population floral color polymorphism is poorly
      understood. Divergent selection, mediated by different pollinators or by both
      mutualists and antagonists, may create and maintain such polymorphism, but it has
      rarely been shown to result from differential behavior of one pollinator. We
      tested whether different behaviors of the same pollinators in morning and evening
      are associated with dimorphic floral trait in Linum pubescens, a Mediterranean
      annual plant that exhibits variable within-population frequencies of dark- and
      light-colored flower tubes. Usia bicolor bee-flies, the major pollinators of L.
      pubescens, are mostly feeding in the flower in the morning, while in the evening
      they are mostly visiting the flowers for mating. In 2 years of studying L.
      pubescens in a single large population in the Carmel, Israel, we found in one
      year that dark-centered flowers received significantly higher fraction of visits
      in the morning. Fitness was positively affected by number of visits, but no
      fitness differences were found between tube-color morphs, suggesting that both
      morphs have similar pollination success. Using mediation analysis, we found that
      flower size was under positive directional pollinator-mediated selection in both
      years, but pollinator behavior did not explain entirely this selection, which was
      possibly mediated also by other agents, such as florivores or a-biotic stresses.
      While most pollinator-mediated selection studies show that flower size signals
      food reward, in L. pubescens, it may also signal for mating place, which may
      drive positive selection. While flower size found to be under pollinator-mediated
      selection in L. pubescens, differential behavior of the pollinators in morning
      and evening did not seem to explain flower color polymorphism.

PMID- 29375783
TI  - What factors potentially influence the ability of phylogenetic distance to
      predict trait dispersion in a temperate forest?
AB  - Although phylogenetic-based approaches have been frequently used to infer
      ecological processes, they have been increasingly criticized in recent years. To
      date, the factors that affect phylogenetic signals and further the ability of
      phylogenetic distance to predict trait dispersion have been assumed but not
      empirically tested. Therefore, we investigate which factors potentially influence
      the ability of phylogenetic distance to predict trait dispersion. We quantified
      the phylogenetic and trait dispersions across size classes and spatial scales in
      a 9-ha old-growth temperate forest dynamics plot in northeastern China.
      Phylogenetic signals at the community level were generally lower than those at
      the species pool level, and phylogenetically clustered communities showed lower
      phylogenetic signals than did overdispersed communities. This pattern might
      explain the other three findings of our study. First, phylogenetically
      overdispersed communities performed better at predicting trait dispersion than
      did clustered communities. Second, the mean pairwise distance (MPD)-based metric
      exhibited a stronger correlation with trait dispersion than did the mean nearest
      taxon distance (MNTD)-based metric. Finally, the MNTD-based metric showed that
      the prediction accuracy for trait dispersion decreased with increasing spatial
      scales, whereas its effects were weak on the MPD-based metric. In addition,
      phylogeny could not determine the dispersions of all functional axes but was able
      to predict certain traits depending on whether they were evolutionarily
      conserved. These results were conserved when we removed the effects of space and
      environment. Our findings highlighted that using phylogenetic distance as a proxy
      of trait similarity might work in a temperate forest depending on the species in
      local communities sampled from total pool as well as the traits measured.
      Utilizing these rules, we should rethink the conclusions of previous studies that
      were based on phylogenetic-based approaches.

PMID- 29375784
TI  - Moose selecting for specific nutritional composition of birch places limits on
      food acceptability.
AB  - Despite decades of intense research, it remains largely unsolved which
      nutritional factors underpin food selection by large herbivores in the wild. We
      measured nutritional composition of birch foliage (Betula pubescens) available
      to, and used by, moose (Alces alces) in natural settings in two neighboring
      regions with contrasting animal body mass. This readily available food source is
      a staple food item in the diet of moose in the high-fitness region, but
      apparently underutilized by moose in the low-fitness region. Available birch
      foliage in the two regions had similar concentrations of macronutrients (crude
      protein [CP], fiber fractions, and water-soluble carbohydrates [WSC]), although a
      notably lower variation of WSC in the low-fitness region. For minerals, there
      were several area differences: available birch foliage in the low-fitness region
      had less Mg (depending on year) and P, but more Ca, Zn, Cu, and Mn. It also had
      higher concentrations of some plant secondary metabolites: chlorogenic acids,
      quercetins, and especially MeOH-soluble condensed tannins. Despite the area
      differences in available foliage, we found the same nutritional composition of
      birch foliage used in the two regions. Compared to available birch foliage, moose
      consistently used birch foliage with more CP, more structural fiber (mainly
      hemicellulose), less WSC, higher concentrations of several minerals (Ca, Zn, K,
      Mn, Cu), and lower concentrations of some secondary metabolites (most
      importantly, MeOH-soluble condensed tannins). Our study conceptually supports the
      nutrient-balancing hypothesis for a large herbivore: within a given temporal
      frame, moose select for plant material that matches a specific nutritional
      composition. As our data illustrate, different moose populations may select for
      the same composition even when the nutritional composition available in a given
      food source varies between their living areas. Such fastidiousness limits the
      proportion of available food that is acceptable to the animal and has bearings on
      our understanding and application of the concept of carrying capacity.

PMID- 29375785
TI  - Long-distance dispersal or postglacial contraction? Insights into disjunction
      between Himalaya-Hengduan Mountains and Taiwan in a cold-adapted herbaceous
      genus, Triplostegia.
AB  - Current disjunct patterns can result from long-distance dispersal or postglacial
      contraction. We herein investigate the evolutionary history of Triplostegia to
      elucidate the disjunction between the Himalaya-Hengduan Mountain region (HHM) and
      Taiwan (TW). Genetic structure of Triplostegia was investigated for 48
      populations using sequences from five chloroplast loci and the ribosomal nuclear
      internal transcribed spacer. Divergence time estimation, ancestral area
      reconstruction, and species distribution modeling (SDM) were employed to examine
      the biogeographic history of Triplostegia. Substantial genetic differentiation
      among populations from southwestern China (SW), Central China (CC), and TW was
      detected. Triplostegia was inferred to have originated in SW, and diversification
      began during the late Miocene; CC was colonized in the mid-Pliocene, and TW was
      finally colonized in the early Pleistocene. SDM suggested an expansion of
      climatically suitable areas during the Last Glacial Maximum and range contraction
      during the Last interglacial in Triplostegia. Disjunction between HHM and TW in
      Triplostegia is most likely the consequence of topographic isolation and
      postglacial contraction. The potential climatic suitability areas for
      Triplostegia by 2070s (2061-2080) are predicted to slightly shrink and move
      northward. With continued global warming and human-induced deforestation,
      extinction risk may increase for the cold-adapted species, and appropriate
      strategies should be employed for ecosystem conservation.

PMID- 29375786
TI  - Traits and climate are associated with first flowering day in herbaceous species
      along elevational gradients.
AB  - Phenological responses to changing temperatures are known as "fingerprints of
      climate change," yet these reactions are highly species specific. To assess
      whether different plant characteristics are related to these species-specific
      responses in flowering phenology, we observed the first flowering day (FFD) of
      ten herbaceous species along two elevational gradients, representing temperature
      gradients. On the same populations, we measured traits being associated with (1)
      plant performance (specific leaf area), (2) leaf biochemistry (leaf C, N, P, K,
      and Mg content), and (3) water-use efficiency (stomatal pore area index and
      stable carbon isotopes concentration). We found that as elevation increased, FFD
      was delayed for all species with a highly species-specific rate. Populations at
      higher elevations needed less temperature accumulation to start flowering than
      populations of the same species at lower elevations. Surprisingly, traits
      explained a higher proportion of variance in the phenological data than
      elevation. Earlier flowering was associated with higher water-use efficiency,
      higher leaf C, and lower leaf P content. In addition to that, the intensity of
      shifts in FFD was related to leaf N and K. These results propose that traits have
      a high potential in explaining phenological variations, which even surpassed the
      effect of temperature changes in our study. Therefore, they have a high potential
      to be included in future analyses studying the effects of climate change and will
      help to improve predictions of vegetation changes.

PMID- 29375787
TI  - Size advantage for male function and size-dependent sex allocation in Ambrosia
      artemisiifolia, a wind-pollinated plant.
AB  - In wind-pollinated plants, male-biased sex allocation is often positively
      associated with plant size and height. However, effects of size (biomass or
      reproductive investment) and height were not separated in most previous studies.
      Here, using experimental populations of monoecious plants, Ambrosia
      altemisiifolia, we examined (1) how male and female reproductive investments (MRI
      and FRI) change with biomass and height, (2) how MRI and height affect male
      reproductive success (MRS) and pollen dispersal, and (3) how height affects seed
      production. Pollen dispersal kernel and selection gradients on MRS were estimated
      by 2,102 seeds using six microsatellite markers. First, MRI increased with
      height, but FRI did not, suggesting that sex allocation is more male-biased with
      increasing plant height. On the other hand, both MRI and FRI increased with
      biomass but often more greatly for FRI, and consequently, sex allocation was
      often female-biased with biomass. Second, MRS increased with both height and MRI,
      the latter having the same or larger effect on MRS. Estimated pollen dispersal
      kernel was fat-tailed, with the maximum distance between mates tending to
      increase with MRI but not with height. Third, the number of seeds did not
      increase with height. Those findings showed that the male-biased sex allocation
      in taller plants of A. artemisiifolia is explained by a direct effect of height
      on MRS.

PMID- 29375788
TI  - Simulations inform design of regional occupancy-based monitoring for a sparsely
      distributed, territorial species.
AB  - Sparsely distributed species attract conservation concern, but insufficient
      information on population trends challenges conservation and funding
      prioritization. Occupancy-based monitoring is attractive for these species, but
      appropriate sampling design and inference depend on particulars of the study
      system. We employed spatially explicit simulations to identify minimum levels of
      sampling effort for a regional occupancy monitoring study design, using white
      headed woodpeckers (Picoides albolvartus), a sparsely distributed, territorial
      species threatened by habitat decline and degradation, as a case study. We
      compared the original design with commonly proposed alternatives with varying
      targets of inference (i.e., species range, space use, or abundance) and spatial
      extent of sampling. Sampling effort needed to achieve adequate power to observe a
      long-term population trend (>=80% chance to observe a 2% yearly decline over 20
      years) with the previously used study design consisted of annually monitoring
      >=120 transects using a single-survey approach or >=90 transects surveyed twice
      per year using a repeat-survey approach. Designs that shifted inference toward
      finer-resolution trends in abundance and extended the spatial extent of sampling
      by shortening transects, employing a single-survey approach to monitoring, and
      incorporating a panel design (33% of units surveyed per year) improved power and
      reduced error in estimating abundance trends. In contrast, efforts to monitor
      coarse-scale trends in species range or space use with repeat surveys provided
      extremely limited statistical power. Synthesis and applications. Sampling
      resolutions that approximate home range size, spatially extensive sampling, and
      designs that target inference of abundance trends rather than range dynamics are
      probably best suited and most feasible for broad-scale occupancy-based monitoring
      of sparsely distributed territorial animal species.

PMID- 29375789
TI  - Quantified reproductive isolation in Heliconius butterflies: Implications for
      introgression and hybrid speciation.
AB  - Heliconius butterflies have become a model for the study of speciation with gene
      flow. For adaptive introgression to take place, there must be incomplete barriers
      to gene exchange that allow interspecific hybridization and multiple generations
      of backcrossing. The recent publication of estimates of individual components of
      reproductive isolation between several species of butterflies in the Heliconius
      melpomene-H. cydno clade allowed us to calculate total reproductive isolation
      estimates for these species. According to these estimates, the butterflies are
      not as promiscuous as has been implied. Differences between species are
      maintained by intrinsic mechanisms, while reproductive isolation of geographical
      races within species is mainly due to allopatry. We discuss the implications of
      this strong isolation for basic aspects of the hybrid speciation with
      introgression hypothesis.

PMID- 29375790
TI  - Plant community and soil conditions individually affect soil microbial community
      assembly in experimental mesocosms.
AB  - Soils harbor large, diverse microbial communities critical for local and global
      ecosystem functioning that are controlled by multiple and poorly understood
      processes. In particular, while there is observational evidence of relationships
      between both biotic and abiotic conditions and microbial composition and
      diversity, there have been few experimental tests to determine the relative
      importance of these two sets of factors at local scales. Here, we report the
      results of a fully factorial experiment manipulating soil conditions and plant
      cover on old-field mesocosms across a latitudinal gradient. The largest
      contributor to beta diversity was site-to-site variation, but, having corrected
      for that, we observed significant effects of both plant and soil treatments on
      microbial composition. Separate phyla were associated with each treatment type,
      and no interactions between soil and plant treatment were observed. Individual
      soil characteristics and biotic parameters were also associated with overall beta
      diversity patterns and phyla abundance. In contrast, soil microbial diversity was
      only associated with site and not experimental treatment. Overall, plant
      community treatment explained more variation than soil treatment, a result not
      previously appreciated because it is difficult to dissociate plant community
      composition and soil conditions in observational studies across gradients. This
      work highlights the need for more nuanced, multifactorial experiments in
      microbial ecology and in particular indicates a greater focus on relationships
      between plant composition and microbial composition during community assembly.

PMID- 29375792
TI  - Comparing the effects of even- and uneven-aged silviculture on ecological
      diversity and processes: A review.
AB  - With an increasing pressure on forested landscapes, conservation areas may fail
      to maintain biodiversity if they are not supported by the surrounding managed
      forest matrix. Worldwide, forests are managed by one of two broad approaches-even
      and uneven-aged silviculture. In recent decades, there has been rising public
      pressure against the systematic use of even-aged silviculture (especially clear
      cutting) because of its perceived negative esthetic and ecological impacts. This
      led to an increased interest for uneven-aged silviculture. However, to date,
      there has been no worldwide ecological comparison of the two approaches, based on
      multiple indicators. Overall, for the 99 combinations of properties or processes
      verified (one study may have evaluated more than one property or process), we
      found nineteen (23) combinations that clearly showed uneven-aged silviculture
      improved the evaluated metrics compared to even-aged silviculture, eleven (16)
      combinations that showed the opposite, and 60 combinations that were equivocal.
      Furthermore, many studies were based on a limited study design without either a
      timescale (44 of the 76) or spatial (54 of the 76) scale consideration. Current
      views that uneven-aged silviculture is better suited than even-aged silviculture
      for maintaining ecological diversity and processes are not substantiated by our
      analyses. Our review, by studying a large range of indicators and many different
      taxonomic groups, also clearly demonstrates that no single approach can be relied
      on and that both approaches are needed to ensure a greater number of positive
      impacts. Moreover, the review clearly highlights the importance of maintaining
      protected areas as some taxonomic groups were found to be negatively affected no
      matter the management approach used. Finally, our review points to a lack of
      knowledge for determining the use of even- or uneven-aged silviculture in terms
      of both their respective proportion in the landscape and their spatial agency.

PMID- 29375791
TI  - Impact of long-term chromosomal shuffling on the multispecies coalescent analysis
      of two anthropoid primate lineages.
AB  - Multispecies coalescent (MSC) theory assumes that gene trees inferred from
      individual loci are independent trials of the MSC process. As genes might be
      physically close in syntenic associations spanning along chromosome regions,
      these assumptions might be flawed in evolutionary lineages with substantial
      karyotypic shuffling. Neotropical primates (NP) represent an ideal case for
      assessing the performance of MSC methods in such scenarios because chromosome
      diploid number varies significantly in this lineage. To this end, we investigated
      the effect of sequence length on the theoretical expectations of MSC model, as
      well as the results of coalescent-based tree inference methods. This was carried
      out by comparing NP with hominids, a lineage in which chromosome macrostructure
      has been stable for at least 15 million years. We found that departure from the
      MSC model in Neotropical primates decreased with smaller sequence fragments,
      where sites sharing the same evolutionary history were more frequently found than
      in longer fragments. This scenario probably resulted from extensive karyotypic
      rearrangement occurring during the radiation of NP, contrary to the comparatively
      stable chromosome evolution in hominids.

PMID- 29375793
TI  - Feather mite abundance varies but symbiotic nature of mite-host relationship does
      not differ between two ecologically dissimilar warblers.
AB  - Feather mites are obligatory ectosymbionts of birds that primarily feed on the
      oily secretions from the uropygial gland. Feather mite abundance varies within
      and among host species and has various effects on host condition and fitness, but
      there is little consensus on factors that drive variation of this symbiotic
      system. We tested hypotheses regarding how within-species and among-species
      traits explain variation in both (1) mite abundance and (2) relationships between
      mite abundance and host body condition and components of host fitness
      (reproductive performance and apparent annual survival). We focused on two
      closely related (Parulidae), but ecologically distinct, species: Setophaga
      cerulea (Cerulean Warbler), a canopy dwelling open-cup nester, and Protonotaria
      citrea (Prothonotary Warbler), an understory dwelling, cavity nester. We
      predicted that feather mites would be more abundant on and have a more parasitic
      relationship with P. citrea, and within P. citrea, females and older individuals
      would harbor greater mite abundances. We captured, took body measurements,
      quantified feather mite abundance on individuals' primaries and rectrices, and
      monitored individuals and their nests to estimate fitness. Feather mite abundance
      differed by species, but in the opposite direction of our prediction. There was
      no relationship between mite abundance and any measure of body condition or
      fitness for either species or sex (also contrary to our predictions). Our results
      suggest that species biology and ecological context may influence mite abundance
      on hosts. However, this pattern does not extend to differential effects of mites
      on measures of host body condition or fitness.

PMID- 29375794
TI  - Ecological effects of sex differ with trophic positions in a simple food web.
AB  - Sexual differences in parental investment, predation pressure, and foraging
      efforts are common in nature and affect the trophic flow in food webs.
      Specifically, the sexual differences in predator and prey behavior change in
      trophic inflow and outflow, respectively, while those in parental investment
      alter the reproductive allocation of acquired resources in the population.
      Consequently, these factors may play an important role in determining the system
      structure and persistence. However, few studies have examined how sexual
      differences in trophic flow affect food web dynamics. In this study, I show the
      ecological role of sex by explicitly incorporating sexual differences in trophic
      flow into a three-species food web model. The results demonstrated that the
      ecological waste of males, that is, the amount of trophic inflow into males with
      less parental investment, plays an important role in system persistence and
      structure. In particular, the synergy between sexual differences in parental
      investment and trophic inflows and outflows is important in determining web
      persistence: Significant impacts of male-biased trophic flows require the
      condition of anisogamy. In addition, the dynamic effects of the ecological waste
      of males differ with trophic level: The coexistence of a food web occurs more
      frequently with biased inflows into predator males, but occurs less frequently
      with biased inflows into consumer males. The model analysis indicates that
      investigating the pattern of sexual differences among trophic positions can
      enrich our understanding of food web persistence and structure in the real world.

PMID- 29375795
TI  - Coexistence through mutualist-dependent reversal of competitive hierarchies.
AB  - Mechanisms that allow for the coexistence of two competing species that share a
      trophic level can be broadly divided into those that prevent competitive
      exclusion of one species within a local area, and those that allow for
      coexistence only at a regional level. While the presence of aphid-tending ants
      can change the distribution of aphids among host plants, the role of mutualistic
      ants has not been fully explored to understand coexistence of multiple aphid
      species in a community. The tansy plant (Tanacetum vulgare) hosts three common
      and specialized aphid species, with only one being tended by ants. Often, these
      aphids species will not coexist on the same plant but will coexist across
      multiple plant hosts in a field. In this study, we aim to understand how
      interactions with mutualistic ants and predators affect the coexistence of
      multiple species of aphid herbivores on tansy. We show that the presence of ants
      drives community assembly at the level of individual plant, that is, the local
      community, by favoring one ant-tended species, Metopeurum fuscoviride, while
      preying on the untended Macrosiphoniella tanacetaria and, to a lesser extent,
      Uroleucon tanaceti. Competitive hierarchies without ants were very different from
      those with ants. At the regional level, multiple tansy plants provide a habitat
      across which all aphid species can coexist at the larger spatial scale, while
      being competitively excluded at the local scale. In this case, ant mutualist
      dependent reversal of the competitive hierarchy can drive community dynamics in a
      plant-aphid system.

PMID- 29375796
TI  - Interspecies introgressive hybridization in spiny frogs Quasipaa (Family
      Dicroglossidae) revealed by analyses on multiple mitochondrial and nuclear genes.
AB  - Introgression may lead to discordant patterns of variation among loci and traits.
      For example, previous phylogeographic studies on the genus Quasipaa detected
      signs of genetic introgression from genetically and morphologically divergent
      Quasipaa shini or Quasipaa spinosa. In this study, we used mitochondrial and
      nuclear DNA sequence data to verify the widespread introgressive hybridization in
      the closely related species of the genus Quasipaa, evaluate the level of genetic
      diversity, and reveal the formation mechanism of introgressive hybridization. In
      Longsheng, Guangxi Province, signs of asymmetrical nuclear introgression were
      detected between Quasipaa boulengeri and Q. shini. Unidirectional mitochondrial
      introgression was revealed from Q. spinosa to Q. shini. By contrast,
      bidirectional mitochondrial gene introgression was detected between Q. spinosa
      and Q. shini in Lushan, Jiangxi Province. Our study also detected ancient
      hybridizations between a female Q. spinosa and a male Q. jiulongensis in Zhejiang
      Province. Analyses on mitochondrial and nuclear genes verified three candidate
      cryptic species in Q. spinosa, and a cryptic species may also exist in Q.
      boulengeri. However, no evidence of introgressive hybridization was found between
      Q. spinosa and Q. boulengeri. Quasipaa exilispinosa from all the sampling
      localities appeared to be deeply divergent from other communities. Our results
      suggest widespread introgressive hybridization in closely related species of
      Quasipaa and provide a fundamental basis for illumination of the forming
      mechanism of introgressive hybridization, classification of species, and
      biodiversity assessment in Quasipaa.

PMID- 29375797
TI  - De novo assembly and characterization of the Hucho taimen transcriptome.
AB  - Taimen (Hucho taimen) is an important ecological and economic species that is
      classified as vulnerable by the IUCN Red List of Threatened Species; however,
      limited genomic information is available on this species. RNA-Seq is a useful
      tool for obtaining genetic information and developing genetic markers for
      nonmodel species in addition to its application in gene expression profiling. In
      this study, we performed a comprehensive RNA-Seq analysis of taimen. We obtained
      157 M clean reads (14.7 Gb) and used them to de novo assemble a high-quality
      transcriptome with a N50 size of 1,060 bp. In the assembly, 82% of the
      transcripts were annotated using several databases, and 14,666 of the transcripts
      contained a full open reading frame. The assembly covered 75% of the transcripts
      of Atlantic salmon and 57.3% of the protein-coding genes of rainbow trout. To
      learn about the genome evolution, we performed a systematic comparative analysis
      across 11 teleosts including eight salmonids and found 313 unique gene families
      in taimen. Using Atlantic salmon and rainbow trout transcriptomes as the
      background, we identified 250 positive selection transcripts. The pathway
      enrichment analysis revealed a unique characteristic of taimen: It possesses more
      immune-related genes than Atlantic salmon and rainbow trout; moreover, some genes
      have undergone strong positive selection. We also developed a pipeline for
      identifying microsatellite marker genotypes in samples and successfully
      identified 24 polymorphic microsatellite markers for taimen. These data and tools
      are useful for studying conservation genetics, phylogenetics, evolution among
      salmonids, and selective breeding for threatened taimen.

PMID- 29375798
TI  - Selection on the morphology-physiology-performance nexus: Lessons from freshwater
      stickleback morphs.
AB  - Conspecifics inhabiting divergent environments frequently differ in morphology,
      physiology, and performance, but the interrelationships amongst traits and with
      Darwinian fitness remains poorly understood. We investigated population
      differentiation in morphology, metabolic rate, and swimming performance in three
      spined sticklebacks (Gasterosteus aculeatus L.), contrasting a marine/ancestral
      population with two distinct freshwater morphotypes derived from it: the
      "typical" low-plated morph, and a unique "small-plated" morph. We test the
      hypothesis that similar to plate loss in other freshwater populations, reduction
      in lateral plate size also evolved in response to selection. Additionally, we
      test how morphology, physiology, and performance have evolved in concert as a
      response to differences in selection between marine and freshwater environments.
      We raised pure-bred second-generation fish originating from three populations and
      quantified their lateral plate coverage, burst- and critical swimming speeds, as
      well as standard and active metabolic rates. Using a multivariate QST-FST
      framework, we detected signals of directional selection on metabolic physiology
      and lateral plate coverage, notably demonstrating that selection is responsible
      for the reduction in lateral plate coverage in a small-plated stickleback
      population. We also uncovered signals of multivariate selection amongst all
      bivariate trait combinations except the two metrics of swimming performance.
      Divergence between the freshwater and marine populations exceeded neutral
      expectation in morphology and in most physiological and performance traits,
      indicating that adaptation to freshwater habitats has occurred, but through
      different combinations of traits in different populations. These results
      highlight both the complex interplay between morphology, physiology and
      performance in local adaptation, and a framework for their investigation.

PMID- 29375799
TI  - Partitioning of herbivore hosts across time and food plants promotes
      diversification in the Megastigmus dorsalis oak gall parasitoid complex.
AB  - Communities of insect herbivores and their natural enemies are rich and
      ecologically crucial components of terrestrial biodiversity. Understanding the
      processes that promote their origin and maintenance is thus of considerable
      interest. One major proposed mechanism is ecological speciation through host
      associated differentiation (HAD), the divergence of a polyphagous species first
      into ecological host races and eventually into more specialized daughter species.
      The rich chalcid parasitoid communities attacking cynipid oak gall wasp hosts are
      structured by multiple host traits, including food plant taxon, host gall
      phenology, and gall structure. Here, we ask whether the same traits structure
      genetic diversity within supposedly generalist parasitoid morphospecies. We use
      mitochondrial DNA sequences and microsatellite genotypes to quantify HAD for
      Megastigmus (Bootanomyia) dorsalis, a complex of two apparently generalist
      cryptic parasitoid species attacking oak galls. Ancient Balkan refugial
      populations showed phenological separation between the cryptic species, one
      primarily attacking spring galls, and the other mainly attacking autumn galls.
      The spring species also contained host races specializing on galls developing on
      different host-plant lineages (sections Cerris vs. Quercus) within the oak genus
      Quercus. These results indicate more significant host-associated structuring
      within oak gall parasitoid communities than previously thought and support
      ecological theory predicting the evolution of specialist lineages within
      generalist parasitoids. In contrast, UK populations of the autumn cryptic species
      associated with both native and recently invading oak gall wasps showed no
      evidence of population differentiation, implying rapid recruitment of native
      parasitoid populations onto invading hosts, and hence potential for natural
      biological control. This is of significance given recent rapid range expansion of
      the economically damaging chestnut gall wasp, Dryocosmus kuriphilus, in Europe.

PMID- 29375800
TI  - Shifts in frog size and phenology: Testing predictions of climate change on a
      widespread anuran using data from prior to rapid climate warming.
AB  - Changes in body size and breeding phenology have been identified as two major
      ecological consequences of climate change, yet it remains unclear whether climate
      acts directly or indirectly on these variables. To better understand the
      relationship between climate and ecological changes, it is necessary to determine
      environmental predictors of both size and phenology using data from prior to the
      onset of rapid climate warming, and then to examine spatially explicit changes in
      climate, size, and phenology, not just general spatial and temporal trends. We
      used 100 years of natural history collection data for the wood frog, Lithobates
      sylvaticus with a range >9 million km2, and spatially explicit environmental data
      to determine the best predictors of size and phenology prior to rapid climate
      warming (1901-1960). We then tested how closely size and phenology changes
      predicted by those environmental variables reflected actual changes from 1961 to
      2000. Size, phenology, and climate all changed as expected (smaller, earlier, and
      warmer, respectively) at broad spatial scales across the entire study range.
      However, while spatially explicit changes in climate variables accurately
      predicted changes in phenology, they did not accurately predict size changes
      during recent climate change (1961-2000), contrary to expectations from numerous
      recent studies. Our results suggest that changes in climate are directly linked
      to observed phenological shifts. However, the mechanisms driving observed body
      size changes are yet to be determined, given the less straightforward
      relationship between size and climate factors examined in this study. We
      recommend that caution be used in "space-for-time" studies where measures of a
      species' traits at lower latitudes or elevations are considered representative of
      those under future projected climate conditions. Future studies should aim to
      determine mechanisms driving trends in phenology and body size, as well as the
      impact of climate on population density, which may influence body size.

PMID- 29375801
TI  - Evaluating behavioral responses of nesting lesser snow geese to unmanned aircraft
      surveys.
AB  - Unmanned aircraft systems (UAS) are relatively new technologies gaining
      popularity among wildlife biologists. As with any new tool in wildlife science,
      operating protocols must be developed through rigorous protocol testing. Few
      studies have been conducted that quantify the impacts UAS may have on
      unhabituated individuals in the wild using standard aerial survey protocols. We
      evaluated impacts of unmanned surveys by measuring UAS-induced behavioral
      responses during the nesting phase of lesser snow geese (Anser caerulescens
      caerulescens) in Wapusk National Park, Manitoba, Canada. We conducted surveys
      with a fixed-wing Trimble UX5 and monitored behavioral changes via discreet
      surveillance cameras at 25 nests. Days with UAS surveys resulted in decreased
      resting and increased nest maintenance, low scanning, high scanning, head-cocking
      and off-nest behaviors when compared to days without UAS surveys. In the group of
      birds flown over, head-cocking for overhead vigilance was rarely seen prior to
      launch or after landing (mean estimates 0.03% and 0.02%, respectively) but
      increased to 0.56% of the time when the aircraft was flying overhead suggesting
      that birds were able to detect the aircraft during flight. Neither UAS survey
      altitude nor launch distance alone in this study was strong predictors of nesting
      behaviors, although our flight altitudes (>=75 m above ground level) were much
      higher than previously published behavioral studies. Synthesis and applications:
      The diversity of UAS models makes generalizations on behavioral impacts
      difficult, and we caution that researchers should design UAS studies with
      knowledge that some minimal disturbance is likely to occur. We recommend flight
      designs take potential behavioral impacts into account by increasing survey
      altitude where data quality requirements permit. Such flight designs should
      consider a priori knowledge of focal species' behavioral characteristics.
      Research is needed to determine whether any such disturbance is a result of
      visual or auditory stimuli.

PMID- 29375802
TI  - Delayed egg-laying and shortened incubation duration of Arctic-breeding
      shorebirds coincide with climate cooling.
AB  - Biological impacts of climate change are exemplified by shifts in phenology. As
      the timing of breeding advances, the within-season relationships between timing
      of breeding and reproductive traits may change and cause long-term changes in the
      population mean value of reproductive traits. We investigated long-term changes
      in the timing of breeding and within-season patterns of clutch size, egg volume,
      incubation duration, and daily nest survival of three shorebird species between
      two decades. Based on previously known within-season patterns and assuming a
      warming trend, we hypothesized that the timing of clutch initiation would advance
      between decades and would be coupled with increases in mean clutch size, egg
      volume, and daily nest survival rate. We monitored 1,378 nests of western
      sandpipers, semipalmated sandpipers, and red-necked phalaropes at a subarctic
      site during 1993-1996 and 2010-2014. Sandpipers have biparental incubation,
      whereas phalaropes have uniparental incubation. We found an unexpected long-term
      cooling trend during the early part of the breeding season. Three species delayed
      clutch initiation by 5 days in the 2010s relative to the 1990s. Clutch size and
      daily nest survival showed strong within-season declines in sandpipers, but not
      in phalaropes. Egg volume showed strong within-season declines in one species of
      sandpiper, but increased in phalaropes. Despite the within-season patterns in
      traits and shifts in phenology, clutch size, egg volume, and daily nest survival
      were similar between decades. In contrast, incubation duration did not show
      within-season variation, but decreased by 2 days in sandpipers and increased by 2
      days in phalaropes. Shorebirds demonstrated variable breeding phenology and
      incubation duration in relation to climate cooling, but little change in
      nonphenological components of traits. Our results indicate that the breeding
      phenology of shorebirds is closely associated with the temperature conditions on
      breeding ground, the effects of which can vary among reproductive traits and
      among sympatric species.

PMID- 29375804
TI  - Multiple signaling functions of song in a polymorphic species with alternative
      reproductive strategies.
AB  - Vocal traits can be sexually selected to reflect male quality, but may also
      evolve to serve additional signaling functions. We used a long-term dataset to
      examine the signaling potential of song in dimorphic white-throated sparrows
      (Zonotrichia albicollis). We investigated whether song conveys multifaceted
      information about the vocalizing individual, including fitness, species identity,
      individual identity, and morph. We also evaluated whether song traits correlate
      differently with fitness in the two morphs, as the more promiscuous strategy of
      white, relative to tan, morph males might impose stronger sexual selection. Males
      with high song rates achieved higher lifetime reproductive success, and this
      pattern was driven by white morph males. In addition, males that sang songs with
      many notes survived longer, but this pattern was less robust. Thus, song traits
      reflect differences in fitness and may more strongly affect fitness in the white
      morph. Song frequency was unrelated to fitness, body size, or morph, but was
      individual specific and could signal individual identity. Songs of the two morphs
      displayed similar frequency ratios and bandwidths. However, tan morph males sang
      songs with longer first notes, fewer notes, and higher variability. Thus, song
      could be used in morph discrimination. Variation in frequency ratios between
      notes was low and could function in conspecific recognition, but pitch change
      dynamics did differ between four different song types observed. Our results
      support a multiple messages model for white-throated sparrow song, in which
      different song traits communicate discrete information about the vocalizing
      individual.

PMID- 29375803
TI  - Mosquito vector-associated microbiota: Metabarcoding bacteria and eukaryotic
      symbionts across habitat types in Thailand endemic for dengue and other arthropod
      borne diseases.
AB  - Vector-borne diseases are a major health burden, yet factors affecting their
      spread are only partially understood. For example, microbial symbionts can impact
      mosquito reproduction, survival, and vectorial capacity, and hence affect disease
      transmission. Nonetheless, current knowledge of mosquito-associated microbial
      communities is limited. To characterize the bacterial and eukaryotic microbial
      communities of multiple vector species collected from different habitat types in
      disease endemic areas, we employed next-generation 454 pyrosequencing of 16S and
      18S rRNA amplicon libraries, also known as metabarcoding. We investigated pooled
      whole adult mosquitoes of three medically important vectors, Aedes aegypti, Ae.
      albopictus, and Culex quinquefasciatus, collected from different habitats across
      central Thailand where we previously characterized mosquito diversity. Our
      results indicate that diversity within the mosquito microbiota is low, with the
      majority of microbes assigned to one or a few taxa. Two of the most common
      eukaryotic and bacterial genera recovered (Ascogregarina and Wolbachia,
      respectively) are known mosquito endosymbionts with potentially parasitic and
      long evolutionary relationships with their hosts. Patterns of microbial
      composition and diversity appeared to differ by both vector species and habitat
      for a given species, although high variability between samples suggests a strong
      stochastic element to microbiota assembly. In general, our findings suggest that
      multiple factors, such as habitat condition and mosquito species identity, may
      influence overall microbial community composition, and thus provide a basis for
      further investigations into the interactions between vectors, their microbial
      communities, and human-impacted landscapes that may ultimately affect vector
      borne disease risk.

PMID- 29375805
TI  - To feed or not to feed? Bioenergetic impacts of fear-driven behaviors in
      lactating dolphins.
AB  - In mammals, lactation can be the most energetically expensive part of the
      reproductive cycle. Thus, when energy needs are compromised due to predation
      risk, environmental disturbance, or resource scarcity, future reproductive
      success can be impacted. In marine and terrestrial environments, foraging
      behavior is inextricably linked to predation risk. But quantification of foraging
      energetics for lactating animals under predation risk is less understood. In this
      study, we used a spatially explicit individual-based model to study how changes
      in physiology (lactating or not) and the environment (predation risk) affect
      optimal behavior in dolphins. Specifically, we predicted that an adult dolphin
      without calf would incur lower relative energetic costs compared to a lactating
      dolphin with calf regardless of predation risk severity, antipredator behavior,
      or prey quality consumed. Under this state-dependent analysis of risk approach,
      we found predation risk to be a stronger driver in affecting total energetic
      costs (foraging plus locomotor costs) than food quality for both dolphin types.
      Further, contrary to our hypothesis, after accounting for raised energy demands,
      a lactating dolphin with calf does not necessarily have higher relative-to
      baseline costs than a dolphin without calf. Our results indicate that both a
      lactating (with calf) and non-lactating dolphin incur lowered energetic costs
      under a risk-averse behavioral scheme, but consequently suffer from lost foraging
      calories. A lactating dolphin with calf could be particularly worse off in lost
      foraging calories under elevated predation risk, heightened vigilance, and
      increased hiding time relative to an adult dolphin without calf. Further, hiding
      time in refuge could be more consequential than detection distance for both
      dolphin types in estimated costs and losses incurred. In conclusion, our study
      found that reproductive status is an important consideration in analyzing risk
      effects in mammals, especially in animals with lengthy lactation periods and
      those exposed to both biological and nonbiological stressors.

PMID- 29375806
TI  - Green-shifting of SWS2A opsin sensitivity and loss of function of RH2-A opsin in
      flounders, genus Verasper.
AB  - We identified visual opsin genes for three flounder species, including the
      spotted halibut (Verasper variegatus), slime flounder (Microstomus achne), and
      Japanese flounder (Paralichthys olivaceus). Structure and function of opsins for
      the three species were characterized together with those of the barfin flounder
      (V. moseri) that we previously reported. All four flounder species possessed five
      basic opsin genes, including lws, sws1, sws2, rh1, and rh2. Specific features
      were observed in rh2 and sws2. The rh2-a, one of the three subtypes of rh2, was
      absent in the genome of V. variegatus and pseudogenized in V. moseri. Moreover,
      rh2-a mRNA was not detected in M. achne and P. olivaceus, despite the presence of
      a functional reading frame. Analyses of the maximum absorption spectra
      (lambdamax) estimated by in vitro reconstitution indicated that SWS2A of M. achne
      (451.9 nm) and P. olivaceus (465.6 nm) were blue-sensitive, whereas in V.
      variegatus (485.4 nm), it was green-sensitive and comparable to V. moseri (482.3
      nm). Our results indicate that although the four flounder species possess a
      similar opsin gene repertoire, the SWS2A opsin of the genus Verasper is
      functionally green-sensitive, while its overall structure remains conserved as a
      blue-sensitive opsin. Further, the rh2-a function seems to have been reduced
      during the evolution of flounders. lambdamax values of predicted ancestral SWS2A
      of Pleuronectiformes and Pleuronectidae was 465.4 and 462.4 nm, respectively,
      indicating that these were blue-sensitive. Thus, the green-sensitive SWS2A is
      estimated to be arisen in ancestral Verasper genus. It is suggested that the
      sensitivity shift of SWS2A from blue to green may have compensated functional
      reduction in RH2-A.

PMID- 29375808
TI  - Why do we bother? Exploring biologists' motivations to share the details of their
      teaching practice.
AB  - There exists in the UK (and across the global HE sector) a community of
      practitioners who define themselves as biologists but who are more than that.
      They are reflective educators involving themselves in the Scholarship of Teaching
      and Learning (SoTL). In this paper I explore the motivations of these individuals
      to disseminate the detail of their teaching practice. I reflect upon my own
      experience and my observations of the experiences of others and in doing so I
      explore common enablers/disablers to engagement with SoTL. I discuss the prime
      importance of a supportive disciplinary SoTL community and of inspirational
      individuals (peers and managers alike). I reflect upon the tensions that exist
      between teaching and research focused career paths and I consider the possibility
      that this tension is of variable significance. I conclude that the barriers to
      individual engagement with SoTL can be overcome and that the individual drive to
      do so is a powerful one.

PMID- 29375807
TI  - From population connectivity to the art of striping Russian dolls: the lessons
      from Pocillopora corals.
AB  - Here, we examined the genetic variability in the coral genus Pocillopora, in
      particular within the Primary Species Hypothesis PSH09, identified by Gelin,
      Postaire, Fauvelot and Magalon (2017) using species delimitation methods [also
      named Pocillopora eydouxi/meandrina complex sensu, Schmidt-Roach, Miller,
      Lundgren, & Andreakis (2014)] and which was found to split into three secondary
      species hypotheses (SSH09a, SSH09b, and SSH09c) according to assignment tests
      using multi-locus genotypes (13 microsatellites). From a large sampling (2,507
      colonies) achieved in three marine provinces [Western Indian Ocean (WIO),
      Tropical Southwestern Pacific (TSP), and Southeast Polynesia (SEP)], genetic
      structuring analysis conducted with two clustering analyses (structure and DAPC)
      using 13 microsatellites revealed that SSH09a was restricted to the WIO while
      SSH09b and SSH09c were almost exclusively in the TSP and SEP. More surprisingly,
      each SSH split into two to three genetically differentiated clusters, found in
      sympatry at the reef scale, leading to a pattern of nested hierarchical levels
      (PSH > SSH > cluster), each level hiding highly differentiated genetic groups.
      Thus, rather than structured populations within a single species, these three
      SSHs, and even the eight clusters, likely represent distinct genetic lineages
      engaged in a speciation process or real species. The issue is now to understand
      which hierarchical level (SSH, cluster, or even below) corresponds to the species
      one. Several hypotheses are discussed on the processes leading to this pattern of
      mixed clusters in sympatry, evoking formation of reproductive barriers, either by
      allopatric speciation or habitat selection.

PMID- 29375809
TI  - A sequencer coming of age: De novo genome assembly using MinION reads.
AB  - Nanopore technology provides a novel approach to DNA sequencing that yields long,
      label-free reads of constant quality. The first commercial implementation of this
      approach, the MinION, has shown promise in various sequencing applications. This
      review gives an up-to-date overview of the MinION's utility as a de novo
      sequencing device. It is argued that the MinION may allow for portable and
      affordable de novo sequencing of even complex genomes in the near future, despite
      the currently error-prone nature of its reads. Through continuous updates to the
      MinION hardware and the development of new assembly pipelines, both sequencing
      accuracy and assembly quality have already risen rapidly. However, this fast pace
      of development has also lead to a lack of oversight in the expanding landscape of
      analysis tools, as performance evaluations are outdated quickly. Now that the
      MinION is approaching a state of maturity, a thorough comparative benchmarking
      effort of de novo assembly pipelines may be at place. An earlier version of this
      article can be found on BioRxiv.

PMID- 29375810
TI  - Optimal cutoff for the evaluation of insulin resistance through triglyceride
      glucose index: A cross-sectional study in a Venezuelan population.
AB  - Background: Insulin resistance (IR) evaluation is a fundamental goal in clinical
      and epidemiological research. However, the most widely used methods are difficult
      to apply to populations with low incomes. The triglyceride-glucose index (TGI)
      emerges as an alternative to use in daily clinical practice. Therefore the
      objective of this study was to determine an optimal cutoff point for the TGI in
      an adult population from Maracaibo, Venezuela. Methods: This is a sub-study of
      Maracaibo City Metabolic Syndrome Prevalence Study, a descriptive, cross
      sectional study with random and multi-stage sampling. For this analysis, 2004
      individuals of both genders >=18 years old with basal insulin determination and
      triglycerides < 500 mg/dl were evaluated.. A reference population was selected
      according to clinical and metabolic criteria to plot ROC Curves specific for
      gender and age groups to determine the optimal cutoff point according to
      sensitivity and specificity.The TGI was calculated according to the equation: ln
      [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2. Results: The
      TGI in the general population was 4.6+/-0.3 (male: 4.66+/-0.34 vs. female: 4.56+/
      0.33, p=8.93x10 -10). The optimal cutoff point was 4.49, with a sensitivity of
      82.6% and specificity of 82.1% (AUC=0.889, 95% CI: 0.854-0.924). There were no
      significant differences in the predictive capacity of the index when evaluated
      according to gender and age groups. Those individuals with TGI>=4.5 had higher
      HOMA2-IR averages than those with TGI <4.5 (2.48 vs 1.74, respectively, p<0.001).
      Conclusions: The TGI is a measure of interest to identify IR in the general
      population. We propose a single cutoff point of 4.5 to classify individuals with
      IR. Future studies should evaluate the predictive capacity of this index to
      determine atypical metabolic phenotypes, type 2 diabetes mellitus and even
      cardiovascular risk in our population.

PMID- 29375811
TI  - Diagnosis of three different pathogenic microorganisms by gas chromatography-mass
      spectrometry.
AB  - BACKGROUND: Diagnoses  of  respiratory  tract  infections  usually happen  in 
      the  late  phase  of  the  disease  and  usually  result  in  reduction  of  the 
      pathogen  load after broad-spectrum  antibiotic  therapy,  but  not  in
      eradication of the pathogen.  The  development  of a  non-invasive,  fast,  and 
      accurate  method  to  detect  pathogens  has  always  been  of  interest  to 
      researchers  and  clinicians  alike.  Previous studies have shown that bacteria
      produce organic gases.  The  current  study  aimed  to  identify  the  volatile 
      organic  compounds  (VOCs)  produced  by three  respiratory  tract  pathogens, 
      including  Staphylococcus  aureus,  Escherichia  coli  and  Candida  albicans.
      Methods: The  volatile  organic  compounds  (VOCs)  produced  were identified by
      gas chromatography-mass spectrometry(GC-MS), with  prior  collection  of 
      microbial  volatile  compounds  using  solid  phase  microextraction  (SPME) 
      fiber.  The volatile compounds were collected by obtaining bacterial headspace
      samples. RESULTS: Results  showed  that  these  three  organisms  have  various 
      VOCs,  which  were  analyzed  under  different  conditions.  By ignoring common
      VOCs, some species-specific VOCs could be detected.  The most important VOC of E.
      coli was Indole, also some important VOCs produced by S. aureus  were 2,3
      Pentandione,  cis-Dihydro-alpha-terpinyl  acetate,  1-Decyne,  1,3-Heptadiene-3
      yne,  2,5-dimethyl  Pyrazine,  Ethyl  butanoate  and  Cyclohexene,4-ethenyl 
      furthermore,  most  of  identified  compounds  by  C.  albicans are  alcohols.
      CONCLUSIONS: The  detection  of  VOCs  produced  by  infectious  agents  maybe 
      the  key  to  make   a  rapid  and  precise  diagnosis  of  infection,  but  more
      comprehensive  studies  must  be  conducted  in this  regard.

PMID- 29375812
TI  - TicTimer software for measuring tic suppression.
AB  - Woods and Himle developed a standardized tic suppression paradigm (TSP) for the
      experimental setting, to quantify the effects of intentional tic suppression in
      Tourette syndrome. The present article describes a Java program that automates
      record keeping and reward dispensing during the several experimental conditions
      of the TSP. The software can optionally be connected to a commercial reward token
      dispenser to further automate reward delivery to the participant. The timing of
      all tics, 10-second tic-free intervals, and dispensed rewards is recorded in
      plain text files for later analysis. Expected applications include research on
      Tourette syndrome and related disorders.

PMID- 29333239
TI  - The peer review process for awarding funds to international science research
      consortia: a qualitative developmental evaluation.
AB  - Background: Evaluating applications for multi-national, multi-disciplinary, dual
      purpose research consortia is highly complex. There has been little research on
      the peer review process for evaluating grant applications and almost none on how
      applications for multi-national consortia are reviewed. Overseas development
      investments are increasingly being channelled into international science
      consortia to generate high-quality research while simultaneously strengthening
      multi-disciplinary research capacity. We need a better understanding of how such
      decisions are made and their effectiveness. Methods: An award-making institution
      planned to fund 10 UK-Africa research consortia. Over two annual rounds, 34 out
      of 78 eligible applications were shortlisted and reviewed by at least five
      external reviewers before final selections were made by a face-to-face panel. We
      used an innovative approach involving structured, overt observations of award
      making panel meetings and semi-structured interviews with panel members to
      explore how assessment criteria concerning research quality and capacity
      strengthening were applied during the peer review process. Data were coded and
      analysed using pre-designed matrices which incorporated categories relating to
      the assessment criteria. Results: In general the process was rigorous and well
      managed. However, lack of clarity about differential weighting of criteria and
      variations in the panel's understanding of research capacity strengthening
      resulted in some inconsistencies in use of the assessment criteria. Using the
      same panel for both rounds had advantages, in that during the second round
      consensus was achieved more quickly and the panel had increased focus on
      development aspects. Conclusion: Grant assessment panels for such complex
      research applications need to have topic- and context-specific expertise. They
      must also understand research capacity issues and have a flexible but equitable
      and transparent approach. This study has developed and tested an approach for
      evaluating the operation of such panels and has generated lessons that can
      promote coherence and transparency among grant-makers and ultimately make the
      award-making process more effective.

PMID- 29375814
TI  - Comparison of school based and supplemental vaccination strategies in the
      delivery of vaccines to 5-19 year olds in Africa - a systematic review.
AB  - BACKGROUND: Some vaccine preventable diseases (VPDs) still remain a public health
      burden in many African countries. The occurrence of VPDs in all age groups has
      led to the realization of the need to extend routine immunisation services to
      school age children, adolescents and adults. Supplemental immunisation activities
      (SIAs) and school based vaccinations (SBVs) are common strategies used to
      complement the expanded programme on immunisation (EPI). This review aimed to
      assess the effectiveness of SIAs compared to SBVs in the administration of
      vaccines to 5-19 year olds in Africa. METHODS: Systematic review methods were
      used to address our study aim. Several electronic databases were searched up to
      March 30, 2017 for primary studies investigating the delivery of vaccines via
      SIAs or SBVs to 5-19 year olds. This search was complemented by browsing
      reference lists of potential studies obtained from search outputs. Outcomes
      considered for inclusion were: vaccination coverage, costs of the strategy or its
      effect on routine immunisation services. RESULTS: Out of the 4938 studies
      identified, 31 studies met the review inclusion criteria. Both SIAs and SBVs
      showed high vaccination coverage. However, the SIAs reported higher coverage than
      SBVs: 91% (95% CI: 84%, 98%) versus 75% (95% CI: 67%, 83%). In most settings,
      SBVs were reported to be more expensive than SIAs. The SIAs were found to
      negatively affect routine immunisation services. CONCLUSIONS: Both SIAs and SBVs
      are routinely used to complement the EPI in the delivery of vaccines in Africa.
      In settings where school enrolment is suboptimal, as is the case in many African
      countries, our results show SIAs may be more effective in reaching school age
      children and adolescents than SBVs. Our results re-iterate the importance of
      evaluating systematic evidence to best inform African authorities on the optimal
      vaccine delivery strategies targeting school age children and adolescents.

PMID- 29375815
TI  - Anaesthesia for open wrist fracture surgery in adults/elderly.
AB  - Anaesthetic technique for open surgery of acute distal for arm fracture in
      adults/elderly is not well defined. Regional anaesthesia, general anaesthesia or
      a combined general and regional block may be considered. General anaesthetic
      technique, the timing and drug/drug combination for the regional block must also
      be considered. This is a study around published studies assessing anaesthtic
      technique for wrist surgery. A systematic database search was performed and
      papers describing the effect of anaesthetic techniques were included. We found
      sparse evidence for what anaesthetic technique is optimal for open wrist fracture
      repair. In total only six studies were found using our inclusion criteria, which
      all supported the short term, early recovery benefits of regional anaesthesia as
      part of multi-modal analgesia. More protracted outcomes and putting the type of
      block into context of quality of recovery and patients' satisfaction is lacking
      in the literature. The risk for a pain rebound when the block vanishes should
      also be acknowledged. Therefore, further high quality studies are warranted
      concerning the anaesthetic technique for this type of surgery.

PMID- 29375816
TI  - The rise and fall of machine learning methods in biomedical research.
AB  - In the era of explosion in biological data, machine learning techniques are
      becoming more popular in life sciences, including biology and medicine. This
      research note examines the rise and fall of the most commonly used machine
      learning techniques in life sciences over the past three decades.

PMID- 29375817
TI  - Whole exome sequencing identifies a novel homozygous frameshift mutation in the
      ASPM gene, which causes microcephaly 5, primary, autosomal recessive.
AB  - Microcephaly is a genetically heterogeneous disorder and is one of the frequently
      notable conditions in paediatric neuropathology which exists either as a single
      entity or in association with other co-morbidities. More than a single gene is
      implicated in true microcephaly and the list is growing with the recent
      advancements in sequencing technologies. Using massive parallel sequencing, we
      identified a novel frame shift insertion in the abnormal spindle-like
      microcephaly-associated protein gene in a client with true autosomal recessive
      primary microcephaly.  Exome sequencing in the present case helped in identifying
      the true cause behind the disease, which helps in the premarital counselling for
      the sibling to avoid future recurrence of the disorder in the family.

PMID- 29375818
TI  - Molecular mechanisms of macrophage Toll-like receptor-Fc receptor synergy.
AB  - Macrophages (MOs) are a key cell type of both the innate and the adaptive immune
      response and can tailor their response to prevailing conditions. To sense the
      host's status, MOs employ two classes of receptors: Toll-like receptors (TLRs),
      which are sensors for pathogen-derived material, and Fcgamma receptors
      (FcgammaRs) that are detectors of the adaptive immune response. How MOs integrate
      the input from these various sensors is not understood and is the focus of active
      study. Here, we review the recent literature on the molecular mechanisms of TLR
      and FcgR crosstalk and synergy, and discuss the implications of these findings.
      This overview suggests a multilayered mechanism of receptor synergy that allows
      the MO to fine-tune its response to prevailing conditions and provides ideas for
      future investigation.

PMID- 29375820
TI  - Recent advances in the management of priapism.
AB  - Priapism is an uncommon urological emergency that can lead to permanent impotence
      if prompt presentation and medical intervention is not performed. It is a
      breakdown of the usual physiological mechanisms controlling penile tumescence and
      detumescence, leading to a prolonged penile erection (>4 hours) that is unrelated
      to sexual stimulation. Currently, there are three accepted subtypes: ischaemic,
      non-ischaemic, and stuttering priapism, which is also known as recurrent ischemic
      priapism. The aim of treatment is the immediate resolution of the painful
      erection and the preservation of cavernosal smooth muscle function in order to
      prevent cavernosal fibrosis, which can lead to penile shortening and permanent
      erectile dysfunction.

PMID- 29375822
TI  - Hepatoblastoma: current understanding, recent advances, and controversies.
AB  - Introduction: Hepatoblastoma (HB) is the most common primary malignant liver
      neoplasm in children. Its increasing survival rate is related to the progress in
      modern imaging, surgical techniques, and new chemotherapy regimens. Clinical
      approach: One of the past achievements was the development of the pretreatment
      extension of disease (PRETEXT) system. Gradually, the HB therapeutic approach has
      become more individualized with better stratification of patients. Controversies:
      These include the need for preoperative chemotherapy and its optimal duration;
      intensity of preoperative chemotherapy required for locally advanced cases
      (PRETEXT 4); optimal surgical treatment for locally advanced tumors: aggressive
      hepatic resections versus liver transplantation; the role of postoperative
      chemotherapy in the post-transplant setting; the timing and role of
      metastasectomy in patients with disseminated disease who undergo partial liver
      resection; and the prognostic significance of several HB pathology variants.
      Hepatoblastoma biology: Beta-catenin mutations and the beta-catenin/Wnt pathway
      play an important role in HB development. There have been at least two molecular
      signatures in HB published. Unluckily, all of these findings are based on
      relatively small clinical series and require confirmation. Conclusion: The
      treatment of HB started from one and the same therapy for all patients and aimed
      at increased treatment individualization, but the future seems to lie in biology
      driven patient-tailored therapies.

PMID- 29375821
TI  - Antigen-specific Treg cells in immunological tolerance: implications for allergic
      diseases.
AB  - Allergic diseases are chronic inflammatory disorders in which there is failure to
      mount effective tolerogenic immune responses to inciting allergens. The alarming
      rise in the prevalence of allergic diseases in recent decades has spurred
      investigations to elucidate the mechanisms of breakdown in tolerance in these
      disorders and means of restoring it. Tolerance to allergens is critically
      dependent on the generation of allergen-specific regulatory T (Treg) cells, which
      mediate a state of sustained non-responsiveness to the offending allergen. In
      this review, we summarize recent advances in our understanding of mechanisms
      governing the generation and function of allergen-specific Treg cells and their
      subversion in allergic diseases. We will also outline approaches to harness
      allergen-specific Treg cell responses to restore tolerance in these disorders.

PMID- 29375823
TI  - Recent advances in understanding and managing aortic stenosis.
AB  - Over the last few years, treatment of severe symptomatic aortic stenosis in high
      risk patients has drastically changed to adopt a less-invasive approach.
      Transcatheter aortic valve implantation (TAVI) has been developed as a very
      reproducible and safe procedure, as shown in many trials. When compared to
      surgery, TAVI has produced superior, or at least comparable, results, and thus a
      trend to broaden treatment indications to lower-risk patients has erupted as a
      natural consequence, even though there is a lack of long-term evidence. In this
      review, we summarize and underline aspects that still remain unanswered that are
      compulsory if we want to enhance our understanding of this disease.

PMID- 29375819
TI  - Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders.
AB  - Neuronal networks consist of different types of neurons that all play their own
      role in order to maintain proper network function. The two main types of neurons
      segregate in excitatory and inhibitory neurons, which together regulate the flow
      of information through the network. It has been proposed that changes in the
      relative strength in these two opposing forces underlie the symptoms observed in
      psychiatric disorders, including autism and schizophrenia. Here, we review the
      role of alterations to the function of the inhibitory system as a cause of
      psychiatric disorders. First, we explore both patient and post-mortem evidence of
      inhibitory deficiency. We then discuss the function of different interneuron
      subtypes in the network and focus on the central role of a specific class of
      inhibitory neurons, parvalbumin-positive interneurons. Finally, we discuss genes
      known to be affected in different disorders and the effects that mutations in
      these genes have on the inhibitory system in cortex and hippocampus. We conclude
      that alterations to the inhibitory system are consistently identified in animal
      models of psychiatric disorders and, more specifically, that mutations affecting
      the function of parvalbumin-positive interneurons seem to play a central role in
      the symptoms observed in these disorders.

PMID- 29375824
TI  - Early Detection and Chemoprevention of Lung Cancer.
AB  - Despite advances in targeted treatments, lung cancer remains a common and deadly
      malignancy, in part owing to its typical late presentation. Recent developments
      in lung cancer screening and ongoing efforts aimed at early detection, treatment,
      and prevention are promising areas to impact the mortality from lung cancer. In
      the past several years, lung cancer screening with low-dose chest computed
      tomography (CT) was shown to have mortality benefit, and lung cancer screening
      programs have been implemented in some clinical settings. Biomarkers for
      screening, diagnosis, and monitoring of response to therapy are under
      development. Prevention efforts aimed at smoking cessation are as crucial as
      ever, and there have been encouraging findings in recent clinical trials of lung
      cancer chemoprevention. Here we review advancements in the field of lung cancer
      prevention and early malignancy and discuss future directions that we believe
      will result in a reduction in the mortality from lung cancer.

PMID- 29375825
TI  - World Health Organization (WHO) guidelines on use of medically important
      antimicrobials in food-producing animals.
AB  - Background: Antimicrobial use in food-producing animals selects for antimicrobial
      resistance that can be transmitted to humans via food or other transmission
      routes. The World Health Organization (WHO) in 2005 ranked the medical importance
      of antimicrobials used in humans. In late 2017, to preserve the effectiveness of
      medically important antimicrobials for humans, WHO released guidelines on use of
      antimicrobials in food-producing animals that incorporated the latest WHO
      rankings. Methods: WHO commissioned systematic reviews and literature reviews,
      and convened a Guideline Development Group (GDG) of external experts free of
      unacceptable conflicts-of-interest. The GDG assessed the evidence using the
      Grading of Recommendations Assessment, Development and Evaluation (GRADE)
      approach, and formulated recommendations using a structured evidence-to-decision
      approach that considered the balance of benefits and harms, feasibility, resource
      implications, and impact on equity. The resulting guidelines were peer-reviewed
      by an independent External Review Group and approved by the WHO Guidelines Review
      Committee. Results: These guidelines recommend reductions in the overall use of
      medically important antimicrobials in food-producing animals, including complete
      restriction of use of antimicrobials for growth promotion and for disease
      prevention (i.e., in healthy animals considered at risk of infection). These
      guidelines also recommend that antimicrobials identified as critically important
      for humans not be used in food-producing animals for treatment or disease control
      unless susceptibility testing demonstrates the drug to be the only treatment
      option. Conclusions: To preserve the effectiveness of medically important
      antimicrobials, veterinarians, farmers, regulatory agencies, and all other
      stakeholders are urged to adopt these recommendations and work towards
      implementation of these guidelines.

PMID- 29375827
TI  - Clinical Case Reports is celebrating!

PMID- 29375826
TI  - Dietary betaine activates hepatic VTGII expression in laying hens associated with
      hypomethylation of GR gene promoter and enhanced GR expression.
AB  - Background: Vitellogenin (VTG) is a precursor of egg yolk proteins synthesized
      within the liver of oviparous vertebrates. Betaine is an important methyl donor
      that is reported to improve egg production of laying hens with an unclear
      mechanism. In the present study, we fed betaine-supplemented diet (0.5%) to
      laying hens for 4 wk and investigated its effect on VTGII expression in the
      liver. Results: Betaine did not affect chicken weight, but significantly (P <
      0.05) increased egg laying rate accompanied with a significant (P < 0.05)
      increase in hepatic concentration and plasma level of VTGII. Plasma estrogen
      level did not change, but the hepatic expression of estrogen receptor alpha
      (ERalpha) mRNA was significantly (P < 0.05) up-regulated. Betaine did not affect
      the protein content of ERalpha, but significantly (P < 0.05) increased hepatic
      expression of glucocorticoid receptor (GR) at both mRNA and protein levels. Also,
      ERalpha/GR interaction tended to be enhanced in the liver nuclear lysates of
      betaine-supplemented hens as determined by co-immunoprecipitation. Furthermore,
      dietary betaine supplementation significantly increased (P < 0.05) the hepatic
      expression of methyl-transfer enzymes, such as BHMT, GNMT, and DNMT1, which was
      associated with higher SAM/SAH ratio and hypomethylation of GR promoter regions.
      Conclusions: Betaine activates hepatic VTGII expression in association with
      modified DNA methylation of GR gene promoter, GR expression and ERalpha/GR
      interaction. Activation of hepatic VTGII expression may contribute, at least
      partly, to improved egg production in betaine-supplemented hens.

PMID- 29375828
TI  - Co-occurrence of a novel PDGFRB variant and likely pathogenic variant in CASR in
      an individual with extensive intracranial calcifications and hypocalcaemia.
AB  - This case report describes an individual with brain calcifications, cognitive
      decline, motor dysfunction, and hypocalcaemia. Exome sequencing revealed a
      previously reported variant in the CASR gene and a variant of uncertain
      significance in PDGFRB. The clinical phenotype is likely explained by the CASR
      variant, but we discuss how the PDGFRB variant could also participate in the
      phenotype.

PMID- 29375829
TI  - DNA methylation alterations in the genome of a toddler with cri-du-chat syndrome.
AB  - This manuscript reports on genomewide epigenetic alterations in cri-du-chat
      syndrome related to a partial aneusomy of chromosome 5. A systematic analysis of
      these alterations will open up new possibilities for the prognostic evaluation of
      CDCS patients and the development of new therapeutic interventions for reducing
      the severity of the disease.

PMID- 29375830
TI  - Neonatal diabetes mellitus: improved screening and early management of an
      underestimated disease.
AB  - Neonatal diabetes mellitus is underdiagnosed in the neonatal period because of
      the metabolic adaptation capacities of the newborns. However, it is associated
      with increased risk of short- and long-term morbidity; when transient it may
      recurs in adulthood. It is important to improve screening and early management
      with appropriate guidelines.

PMID- 29375831
TI  - Pancreatitis and myocarditis coexistence due to infection by Coxsackie B1 and B4
      viruses.
AB  - Myocarditis can be a rare late manifestation of acute pancreatitis caused by
      Coxsackie virus infection. Clinicians should be aware of potentially life
      threatening myocarditis because immediate recognition and management are the
      cornerstones in achieving a better outcome.

PMID- 29375832
TI  - Successful management of malignant carinal involvement by "side-by-side" method
      of self-expandable metallic stents followed by chemotherapy.
AB  - Bilateral self-expandable metallic stents may be useful in the management of
      malignant carinal involvement and may improve the performance status of patients.
      This strategy may allow patients with poor performance status to receive
      additional chemotherapy.

PMID- 29375833
TI  - Identification of a novel deletion within ALDH3A2 gene in an Iranian Family with
      Sjogren-Larsson Syndrome.
AB  - Sjogren-Larsson syndrome (SLS) is a rare type of congenital ichthyosis with
      neurological problems and intellectual disability. Homozygous mutations in
      ALDH3A2 gene are known to be responsible for this syndrome. Here, we report an
      Iranian family with congenital SLS bearing a novel two-base-pair deletion within
      ALDH3A2 genomic sequence. Our finding expands the mutation spectrum of ALDH3A2
      that is applicable for further molecular studies and management of SLS.

PMID- 29375835
TI  - Liver injury secondary to chest tube placement: a case report of conservative
      management and review of literature.
AB  - Chest tube placement is a routine procedure performed in different medical
      departments. Liver injury is a very rare complication that can occur but can be
      life-threatening. Conservative management can be proposed in stable patient.
      Following guidelines and training physicians should decrease the incidence of
      such complications.

PMID- 29375834
TI  - Functional plurihormonal adrenal oncocytoma: case report and literature review.
AB  - We present a 27-year-old woman with an adrenal oncocytoma. This is a very rare
      entity. We provide a review of the clinical, biochemical and pathological
      features of cases reported in the literature.

PMID- 29375836
TI  - Unexpected disseminated histoplasmosis detected by bone marrow biopsy in a solid
      organ transplant patient.
AB  - Disseminated histoplasmosis and hemophagocytic lymphohistiocytosis show
      overlapping features, which require careful contextual interpretation.
      Histopathologic evaluation can potentially rapidly identify cases of possible
      histoplasmosis. A high index of clinical suspicion, particularly in endemic areas
      and in a setting of immunosuppression, is critical to appropriate diagnosis and
      treatment.

PMID- 29375837
TI  - Successful elimination of premature ventricular contractions by ablation of
      origin and preferential pathway.
AB  - However, the common strategy for eliminating premature ventricular contractions
      (PVCs) is to explore the exit site and ablate, which may be difficult in some
      cases. The origin and the preferential pathway, an insulated pathway connected to
      the exit, may also become targets for eliminating PVCs.

PMID- 29375838
TI  - Metastatic HPV-related oropharyngeal carcinoma cured with chemoradiotherapy:
      importance of pretherapy biomolecular assessment.
AB  - Pretherapy assessment has a crucial role in the management of advanced
      oropharyngeal carcinoma. The case report represents an example of how
      translational research may help to optimize the therapeutic options and to choose
      a well-shaped therapy adapted to the tumor and the patient.

PMID- 29375839
TI  - Diagnosis of benign notochordal cell tumor of the spine: is a biopsy necessary?
AB  - Benign notochordal cell tumor is a benign intraosseous lesion, demonstrates
      characteristic imaging features. The lesion demonstrates low-signal intensity in
      T1-weighted images, high-signal intensity in T2-weighted images, and no
      enhancement with contrast medium in MRI and slight osteosclerosis in CT. If
      typical imaging findings are identified, biopsy is not necessary.

PMID- 29375840
TI  - Oral care and prevention of pneumonia after withdrawal of nasogastric tube
      feeding in three elderly patients with psychiatric disorders.
AB  - We investigated the effect of oral care on the prevention of pneumonia using a
      clinical scoring scale in elderly patients with psychiatric disorders after the
      withdrawal of nasogastric feeding tubes. Notably, oral care was effective in
      preventing pneumonia relapse in these patients.

PMID- 29375841
TI  - Paranasal gossypiboma mimicking an aggressive tumor: a case report.
AB  - Even if gossypibomas are extremely rare in the Oro-Maxillofacial region, they
      should be evoked in bizarre tumors when repeated histology tests are not
      contributive, especially in patients with a history of dento-sinusal surgery. As
      it is recommended in general surgery, gauzes should be carefully counted when
      used in dentistry.

PMID- 29375842
TI  - Visceral leishmaniasis in a patient with diabetes mellitus type 2 and discrete
      bicytopenia.
AB  - An Austrian patient with diabetes mellitus type 2 developed visceral
      leishmaniasis after trips to Spain and Crete, presenting with slight bicytopenia,
      later developing severe pancytopenia. Travel history taking is important due to
      an extended incubation period. Coexistence of diabetes mellitus can impair T
      lymphocyte function and cause higher relapse rates.

PMID- 29375843
TI  - Inflammatory myofibroblastic tumor of the esophagus presenting with hematemesis
      and melaena: a case report and review of literature.
AB  - Esophageal inflammatory myofibroblastic tumors (IMT) are extremely rare, and the
      understanding on the clinical presentation is limited. IMT of esophagus should be
      considered as a differential diagnosis in the context of unexplained upper
      gastrointestinal bleeding and rapidly progressing dysphagia in young patients.

PMID- 29375844
TI  - Unexpected discovery of multiple myeloma following cardiomyopathy.
AB  - We report the case of multiple myeloma of unexpected discovery in an old patient
      admitted to the emergency department of cardiomyopathy. This observation
      emphasizes the need for exploring any anemia before linking it to heart failure
      or kidney disease. Serum protein electrophoresis remains crucial especially in
      the elderly patients.

PMID- 29375845
TI  - Mosaic upd(14)pat in a patient with mild features of Kagami-Ogata syndrome.
AB  - We report a Norwegian girl with mild clinical features of Kagami-Ogata syndrome
      (KOS) and mosaic upd(14)pat. To our knowledge, this is the first report
      describing a mosaic patient with KOS. These results imply that mosaic uniparental
      disomy should be examined in patients with mild features of imprinted disorders.

PMID- 29375846
TI  - The clinical utility of serum free light chain and heavy/light chain assays in
      monitoring disease activity in patients with IgG myeloma after achieving a deep
      response.
AB  - Heavy/light chain (HLC) assay will enable us to evaluate the changes in the
      concentrations of iHLC and uHLC separately and to better identify whether the
      change observed is clonal or reactive. It would therefore aid in decision making
      for earlier implementation or discontinuation of treatment for patients with
      intact immunoglobulin multiple myeloma (MM).

PMID- 29375847
TI  - Tetraploid-diploid mosaicism in a patient with pigmentary anomalies of hair and
      skin: a new dermatologic feature.
AB  - Tetraploid-diploid mosaicism in humans is exceedingly rare. We present an 11-year
      old boy with tetraploid-diploid mosaicism and coexistent hair hypopigmentation
      with skin hypo- and hyperpigmentation. This case expands the current literature
      as we are not aware of previous documentation of this unique combination of
      pigmentary anomalies.

PMID- 29375848
TI  - Plunging ranula: surgical management of case series and the literature review.
AB  - Plunging ranulas are rare; report of this condition is particularly limited in
      our environment. We present case series in children; with all cases having both
      oral and cervical components. It is important to note this type of presentation
      of plunging ranula and their appropriate management.

PMID- 29375849
TI  - EBV-associated hemophagocytic lymphohistiocytosis complicated by severe
      coagulation disorders and opportunistic infections: case report of a survivor.
AB  - The possibility of hemophagocytic lymphohistiocytosis should always be kept in
      mind when examining/treating a patient with fever of unknown origin and sepsis
      like symptoms. Early diagnosis leading to prompt initiation of immunosuppressive
      therapy as well as aggressive supportive care, including correction of
      coagulation abnormalities and treatment of opportunistic infections, can decrease
      mortality.

PMID- 29375850
TI  - Epidemiologic profile and clinical course of four confirmed rickettsiosis cases
      in Southern Mexico during 2016.
AB  - Domestic animals can carry ticks or fleas, which constitute common vectors of
      rickettsial infections. The contact with them should be considered as suggestive
      of rickettsial infections in symptomatic patients. Misdiagnosis might occur in
      regions where other vector-borne diseases are endemic. Anamnesis is essential for
      an accurate clinical diagnosis.

PMID- 29375851
TI  - Association of isochromosome (7)(q10) in Shwachman-Diamond syndrome with the
      severity of cytopenia.
AB  - We report two male siblings with SDS. They have the same compound heterozygous
      mutations. Only one of the siblings acquired cytogenetic abnormality of i(7q) 2
      years after diagnosis, became transfusion-dependent, and underwent allogeneic
      hematopoietic stem cell transplantation. These cases indicate that i(7q) is
      associated with significant cytopenia in SDS patients.

PMID- 29375852
TI  - Liposomal bupivacaine for the management of postsurgical donor site pain in
      patients with burn injuries: a case series from two institutions.
AB  - Donor site pain associated with skin graft procedures is frequently intense and
      difficult to treat. Liposomal bupivacaine, a prolonged-release local anesthetic
      indicated for single-dose administration to produce postsurgical analgesia, may
      be a viable option in managing donor site pain.

PMID- 29375853
TI  - Hashimoto's encephalopathy - presenting with epilepsia partialis continua and a
      frontal lobe lesion.
AB  - We report a case of Hashimoto's encephalopathy (HE), who presented with epilepsia
      partialis continua (EPC) and a frontal lobe lesion. The diagnosis of HE remained
      elusive until the serum thyroid antibodies became positive 7 months after the
      onset of EPC. The histopathology of this frontal lesion showed nonvasculitic
      inflammation.

PMID- 29375854
TI  - Nonhealing scrotal ulceration-an unusual manifestation of TB epididymo-orchitis:
      case report and review of literature.
AB  - The clinical presentation of genitourinary tuberculosis (TB) may be variable and
      a high index of suspicion is required for a timely diagnosis, especially in
      endemic areas. Recurrent scrotal ulcers associated with epididymo-orchitis even
      without other constitutional symptoms should alert the clinician of a possible
      diagnosis of TB.

PMID- 29375855
TI  - Longitudinal report of child with de novo 16p11.2 triplication.
AB  - 16p11.2 deletions and duplications are commonly associated with autism spectrum
      disorder and linked to mirrored phenotypes of physical characteristics and higher
      penetrance for deletions. A male with a rare 16p11.2 triplication demonstrated a
      similar phenotypic presentation to deletion carriers with neurocognitive and
      adaptive skill deficits and above-average physical growth.

PMID- 29375857
TI  - Trochanteric fracture following hip arthrodesis: case presentation.
AB  - Even if the intertrochanteric fracture under an arthrodesis hip is rare and the
      optimal surgical treatment is controversial, we consider that treating this kind
      of fracture with a locked plate was a success.

PMID- 29375856
TI  - Acute lymphoblastic leukemia secondary to myeloproliferative neoplasms or after
      lenalidomide exposure.
AB  - Philadelphia-negative (Ph-) myeloproliferative neoplasms (MPN) do rarely
      transform to acute lymphoblastic leukemia (ALL). While causality is difficult to
      establish, a few cases of ALL arising after exposure to lenalidomide for
      registered indications (multiple myeloma, myelodysplastic syndrome with 5q
      deletion) have been described in the literature.

PMID- 29375858
TI  - A case of herpes simplex virus pneumonia detected by sputum cytodiagnosis.
AB  - A sputum test is noninvasive and simple. It contributed to correct diagnosis of a
      patient with severe acute respiratory failure. We again point out the usefulness
      of sputum cytodiagnosis for differentiating severe pneumonia.

PMID- 29375859
TI  - Congenital methemoglobinemia type II in a 5-year-old boy.
AB  - Congenital Methemoglobinemia is a rare neurologic condition which can mimic other
      diseases such as epilepsy syndromes and leukodystrophies. The responsible gene,
      CYB5R3, is not typically included on commonly order neurologic and epilepsy
      panels. We recommend that laboratories include this gene on these tests which
      often precede larger-scale genetic studies.

PMID- 29375860
TI  - Rare 48, XYYY syndrome: case report and review of the literature.
AB  - 48, XYYY syndrome is a rare condition. A male with 32-year-old and three Y
      chromosomes is described. This syndrome is phenotypically similar to Klinefelter
      syndrome. In this patient, Semi-Klinefelter characteristics such as tall stature,
      teeth dysmorphology, long length of fingers, partial deformity of the joints,
      likewise mental health problems were obvious.

PMID- 29375861
TI  - Basilar impression as complication of Grisel's syndrome.
AB  - Grisel's syndrome presents a rare disease. Here, we present a peculiar case of
      Grisel's syndrome with an unfavorable course developing a basilar impression.
      This highlights the importance of close clinical and radiological follow-up even
      in cases where the course seems uncomplicated.

PMID- 29375862
TI  - The first antenatal diagnosis of KBG syndrome: a microdeletion at chromosome
      16q24.2q24.3 containing multiple genes including ANKRD11 associated with the
      disorder.
AB  - The loss of ANKRD11 gene confirms the diagnosis of KBG syndrome but does not
      elucidate the pediatric phenotype providing a counseling challenge. With the
      expansion of prenatal diagnosis, and the potential to perform whole-exome
      sequencing antenatally, we must describe the genetic abnormalities, antenatal
      ultrasound findings, and phenotype concurrently to facilitate counseling.

PMID- 29375863
TI  - Toothpick ingestion and migration into the liver through the colonic hepatic
      flexure: case presentation, management, and literature review.
AB  - The approach to toothpick ingestion and its complications should not be
      underestimated. The surgeon should be prepared for life-threatening situations
      such as major vascular involvement, as well as highly specialized and technically
      challenging procedures, when the hepatic hilum is involved for instance. Referral
      to tertiary centers is sometimes mandatory.

PMID- 29375864
TI  - Apparent pacemaker dysfunction during peptide receptor radionuclide therapy for
      neuroendocrine tumor.
AB  - This case is a reminder not to overlook rare causes of electrolyte shifts, which
      may cause reversible changes in pacemaker pacing thresholds.

PMID- 29375865
TI  - Clinical whole exome sequencing from dried blood spot identifies novel genetic
      defect underlying asparagine synthetase deficiency.
AB  - We add two novel variants to the existing mutation spectrum of ASNS gene. Loss of
      ASNS function should be suspected in newborns presenting with congenital
      microcephaly, intellectual disability, progressive cerebral atrophy, and
      intractable seizures. Acquisition and sequencing of stored newborn blood spot can
      be a valuable option when no biological samples are available from a deceased
      child.

PMID- 29375866
TI  - Metronidazole caused profound drug-induced immune thrombocytopenia.
AB  - Metronidazole is commonly prescribed and has not been known to cause drug-induced
      immune thrombocytopenia. We have provided clinical and laboratory evidence with
      DDabs that metronidazole can cause drug-induced immune thrombocytopenia (DITP).
      Providers must be aware of metronidazole causing DITP because recognition of
      thrombocytopenia is critical and cessation of the drug should occur promptly.

PMID- 29375867
TI  - A life-devastating cause of gastroenteritis in an immunocompetent host: was it
      suspected?
AB  - A 44-year-old immunocompetent man with gastroenteritis received supportive care
      and empiric antibiotics. After an initial response, he developed septic shock.
      Blood cultures grew Gram-positive bacilli with antibiotic adjustment. However, he
      succumbed within 36 h. After the patient's death, Listeria monocytogenes was
      identified on blood culture.

PMID- 29375869
TI  - A unique case of bilateral hydronephrosis caused by a fecalith.
AB  - This is a unique case that signifies the importance to look beyond the
      genitourinary system for causes of hydronephrosis. In addition, we outline the
      manner in which a fecalith should be addressed.

PMID- 29375868
TI  - Vascular surgery of aortic thrombosis in a dog using Fogarty maneuver - technical
      feasibility.
AB  - Aortic thromboembolism is a rare and life-threatening disease in dogs. This
      report aims to describe the successful surgical treatment by use of a Fogarty
      Thrombectomy Catheter in an 8-year-old patient. The postsurgical intensive care
      therapy to prevent ischemia-reperfusion syndrome is specified, despite poor
      outcome in our case (owner elected euthanasia).

PMID- 29375870
TI  - Orbital plasmablastic lymphoma.
AB  - Plasmablastic lymphoma is an unusual and aggressive form of diffuse large B-cell
      lymphoma, which arises more commonly within the oronasal mucosa. It should be
      considered as a differential diagnosis for rapidly growing periorbital lesions,
      particularly in the context of HIV positivity.

PMID- 29375871
TI  - Fulminant hemolysis in glucose-6-phosphate dehydrogenase deficiency.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder
      affecting some 400 million people worldwide. Though clinically silent, it may
      result in hemolysis on oxidative stress induced by drugs or infections. Viral
      hepatitis A with coexisting G6PD deficiency can be devastating associated with
      severe hemolysis, anemia, renal failure, and hepatic encephalopathy.

PMID- 29375872
TI  - Subcutaneous hematomas from prophylactic heparin use.
AB  - Heparin is an anticoagulant, which is frequently used in hospitalized patients
      for prophylaxis of deep vein thrombosis (DVT). Subcutaneous administration of
      heparin may lead to complications such as bruising, hematoma, and pain at the
      injection site. Hematomas can develop without visible bruising, as in our case.

PMID- 29375873
TI  - Cutaneous diffuse large B-cell lymphoma.
AB  - Cutaneous diffuse large B-cell lymphoma accounts for ~6% of all cutaneous
      lymphomas. It is associated with poor prognosis, and solitary lesions are
      relatively rare. It often requires an aggressive approach with multi-agent
      chemotherapy and radiotherapy. It is important to recognize these cases in order
      to offer rapid and appropriate management.

PMID- 29375874
TI  - Acute fatty liver of pregnancy simulating liver tumor.
AB  - Acute fatty liver of pregnancy (AFLP) is a rare liver disease unique to pregnancy
      that can lead to acute liver failure. Clinicians must have a high index of
      suspicion for AFLP because only early diagnosis and prompt delivery improve
      maternal and fetal prognosis.

PMID- 29375875
TI  - PET/CT imaging in management of concomitant Hodgkin lymphoma and tuberculosis - a
      problem solver tool.
AB  - Infectious lymph nodes mimicking lymphoma is challenging for accurate staging.
      Although 18F-FDG is a nonspecific tracer accumulating not only in tumor cells but
      also in inflammatory tissues, the metabolic features and uptake kinetics give
      valuable information: 18F-FDG PET/CT appears as a useful problem solver tool in
      ambiguous situation.

PMID- 29375876
TI  - Leukemic phase and CSF involvement of diffuse large B-cell lymphoma with a
      complex karyotype including a TP53 deletion.
AB  - Diffuse large B-cell lymphoma in rare instances can present initially in a
      leukemic phase and mimic other lymphoid diseases. In such cases, advanced
      diagnostic testing including immunophenotyping, FISH analysis, and karyotyping
      can help determine the accurate diagnosis which is key in the management of the
      disease.

PMID- 29375877
TI  - Graft-versus-host disease, a rare complication after orthotopic liver
      transplantation.
AB  - Acute graft-versus-host disease (GVHD) after orthotopic liver transplantation
      (OLT) is a rare but fatal complication that poses a major diagnostic and
      therapeutic challenge. Our case highlights the need for further studies to
      develop therapeutic modalities to improve outcomes in patients who develop GHVD
      following OLT.

PMID- 29375878
TI  - Gastrorenal shunt: a cause of hyperammonemia.
AB  - Gastrorenal shunts may induce hyperammonemia. Portosystemic shunts should be
      suspected when hyperammonemia occurs in patients with chronic kidney disease.

PMID- 29375879
TI  - A "tilt" toward cinefluoroscopy.
AB  - Fluoroscopy permits rapid and straightforward assessment of mechanical valve
      function and allows a distinction between normal and malfunctional prostheses,
      acting as a complementary diagnostic step.

PMID- 29375880
TI  - Absolute lymphocyte and neutrophil counts in neonatal ischemic brain injury.
AB  - Objectives: This study aimed to identify differences in absolute neutrophils,
      lymphocytes, and neutrophil-to-lymphocyte ratio between neonates with two forms
      of ischemic brain injury, hypoxic-ischemic encephalopathy, and acute ischemic
      stroke, compared to controls. We also aimed to determine whether this
      neutrophil/lymphocyte response pattern is associated with disease severity or is
      a consequence of the effects of total-body cooling, an approved treatment for
      moderate-to-severe hypoxic-ischemic encephalopathy. Methods: A retrospective
      chart review of 101 neonates with hypoxic-ischemic encephalopathy + total-body
      cooling (n = 26), hypoxic-ischemic encephalopathy (n = 12), acute ischemic stroke
      (n = 15), and transient tachypnea of the newborn (n = 48) was conducted;
      transient tachypnea of the newborn neonates were used as the control group.
      Absolute neutrophil count and absolute lymphocyte count at three time-intervals
      (0-12, 12-36, and 36-60 h after birth) were collected, and neutrophil-to
      lymphocyte ratio was calculated. Results: Hypoxic-ischemic encephalopathy + total
      body cooling neonates demonstrated significant time-interval-dependent changes in
      absolute lymphocyte count and neutrophil-to-lymphocyte ratio levels compared to
      transient tachypnea of the newborn and acute ischemic stroke patients. Pooled
      analysis of absolute lymphocyte count for neonates with acute ischemic stroke and
      hypoxic-ischemic encephalopathy (not hypoxic-ischemic encephalopathy + total-body
      cooling) revealed that absolute lymphocyte count changes occurring at 0-12 h are
      likely due to disease progression, rather than total-body cooling treatment.
      Conclusion: These data suggest that the neutrophil/lymphocyte response is
      modulated following neonatal ischemic brain injury, representing a possible
      target for therapeutic intervention. However, initial severity of hypoxic
      ischemic encephalopathy among these patients could also account for the observed
      changes in the immune response to injury. Thus, additional work to clarify the
      contributions of cooling therapy and disease severity to neutrophil/lymphocyte
      response following hypoxic-ischemic encephalopathy in neonates is warranted.

PMID- 29375881
TI  - The evolving role of traditional birth attendants in maternal health in post
      conflict Africa: A qualitative study of Burundi and northern Uganda.
AB  - Objectives: Many conflict-affected countries are faced with an acute shortage of
      health care providers, including skilled birth attendants. As such, during
      conflicts traditional birth attendants have become the first point of call for
      many pregnant women, assisting them during pregnancy, labour and birth, and in
      the postpartum period. This study seeks to explore how the role of traditional
      birth attendants in maternal health, especially childbirth, has evolved in two
      post-conflict settings in sub-Saharan Africa (Burundi and northern Uganda)
      spanning the period of active warfare to the post-conflict era. Methods: A total
      of 63 individual semi-structured in-depth interviews and 8 focus group
      discussions were held with women of reproductive age, local health care providers
      and staff of non-governmental organisations working in the domain of maternal
      health who experienced the conflict, across urban, semi-urban and rural settings
      in Burundi and northern Uganda. Discussions focused on the role played by
      traditional birth attendants in maternal health, especially childbirth during the
      conflict and how the role has evolved in the post-conflict era. Transcripts from
      the interviews and focus group discussions were analysed by thematic analysis
      (framework approach). Results: Traditional birth attendants played a major role
      in childbirth-related activities in both Burundi and northern Uganda during the
      conflict, with some receiving training and delivery kits from the local health
      systems and non-governmental organisations to undertake deliveries. Following the
      end of the conflict, traditional birth attendants have been prohibited by the
      government from undertaking deliveries in both Burundi and northern Uganda. In
      Burundi, the traditional birth attendants have been integrated within the primary
      health care system, especially in rural areas, and re-assigned the role of 'birth
      companions'. In this capacity they undertake maternal health promotion activities
      within their communities. In northern Uganda, on the other hand, traditional
      birth attendants have not been integrated within the local health system and
      still appear to undertake clandestine deliveries in some rural areas. Conclusion:
      The prominent role of traditional birth attendants in childbirth during the
      conflicts in Burundi and northern Uganda has been dwindling in the post-conflict
      era. Traditional birth attendants can still play an important role in
      facilitating facility and skilled attended births if appropriately integrated
      with the local health system.

PMID- 29375882
TI  - Idiopathic intracranial hypertension as a presenting sign of adrenal
      insufficiency.
AB  - Idiopathic intracranial hypertension is a diagnosis of exclusion defined by
      elevated intracranial pressure without mass lesions or hydrocephalus. Causes of
      idiopathic intracranial hypertension include obesity, vitamin derangements,
      antibiotics, corticosteroids, and autoimmune disorders. Cushing's disease and
      Addison's disease have been associated with idiopathic intracranial hypertension.
      Secondary adrenal insufficiency following withdrawal of inhaled corticosteroids
      has been found to be a relatively common phenomenon. This case describes an 11
      year-old boy who was previously on inhaled corticosteroids for severe asthma who
      presented with secondary adrenal insufficiency after withdrawal of steroids. The
      adrenal insufficiency presented as idiopathic intracranial hypertension. We
      described the hospital course and process of diagnosis for this child with
      secondary adrenal insufficiency following withdrawal of inhaled corticosteroids.
      The association between the discontinuation of this patient's corticosteroids and
      his onset of headache suggests secondary adrenal insufficiency as the most likely
      cause of his idiopathic intracranial hypertension. The gradual improvement in his
      symptoms after steroid replacement further supports this. Due to the significant
      prevalence of children using inhaled corticosteroids, it is important for
      clinicians to be aware of the potential for the withdrawal of these drugs to
      induce hypothalamic-pituitary-adrenal axis suppression.

PMID- 29375883
TI  - Trust and the Ethical Conduct of Community-Engaged Research.
AB  - Community-engaged research (CEnR), which emphasizes equal participation of
      academic and community partners in research, seeks to improve public trust in
      science. Unfortunately, there is a dearth of rigorous empirical research on trust
      as a core component of ethical conduct of CEnR. Drawing on data collected from a
      project on the ethics of CEnR, this commentary discusses benefits and risks of
      trust and uses the concept of embeddedness to explain how public trust in science
      may be increased. We argue that in developing and maintaining trust, partners
      must balance scientific rigor with community relevance and cultural
      appropriateness of research. They must strike a balance between working with the
      same limited pool of trusted partners, which can speed research but slow wider
      acceptance of science, and extending their trust to new partners, which can
      broaden acceptance of science but slow research. Practitioners may facilitate the
      development of trust in science by gradually expanding the pool of partners they
      choose their collaborators from.

PMID- 29375885
TI  - Primary progressive apraxia: an unusual ideomotor syndrome.
AB  - Background: Primary progressive apraxia is a rare form of apraxia in the absence
      of dementia which develops insidiously and is slowly progressive. Most reports of
      patients with apraxia also describe coexisting aphasias or involve additional
      apraxias with affected speech, usually in the setting of neurodegenerative
      diseases such as corticobasal degeneration, Alzheimer's disease or frontotemporal
      dementia. The aim of this report is to describe and demonstrate by video two
      cases of isolated primary progressive ideomotor apraxia seen in our clinic. Case
      presentation: We describe two patients with 2-5 years of progressive difficulty
      using their hands, despite having intact cognition and lack of correlating
      lesions on imaging. Conclusion: We report two cases of primary progressive
      apraxia that may be early presentations of taupathic disease in both patients. In
      both cases, there is isolated profound ideomotor apraxia of the hands, with
      preserved cognition, language skills, muscle power and tone, and gait. There are
      no correlating lesions on imaging.

PMID- 29375884
TI  - Implementation and Evaluation of a Risk-Based Approach to Guide Chronic Kidney
      Disease Care: Protocol for a Multiphase Mixed-Methods Study.
AB  - Background: Risk prediction tools are used in a variety of clinical settings to
      guide patient care, although their use in chronic kidney disease (CKD) care is
      limited. Objectives: To assess the association of a risk-based model of CKD care
      on patient care, satisfaction, outcomes, and cost. Design: Mixed-methods with a
      pre-post design. Setting: We will use mixed-methods and a pre-post design to
      evaluate use of the Kidney Failure Risk Equation (KFRE) to guide CKD care. The
      KFRE will be applied to patients currently followed in nephrology
      multidisciplinary CKD clinics in Alberta, as well as to new patients being
      considered for multidisciplinary care. Patients: Patients with a 2-year risk of
      kidney failure >=10% or estimated glomerular filtration rate (eGFR) <=15
      mL/min/1.73 m2 will be recommended care by a multidisciplinary team coordinated
      by a nurse clinician and nephrologist, with access to other multidisciplinary
      resources including dietitians, pharmacists, and social workers as required.
      Measurements/Methods: Focus groups and interviews will be conducted to
      qualitatively describe patient and provider perspectives of potential barriers
      and facilitators to implementation of the risk-based approach to CKD care.
      Patient and provider surveys will also be used to quantify patient and provider
      satisfaction before and after the intervention. Finally, administrative data will
      be used to evaluate the association between the risk-based approach to care and
      outcomes including health care resource use, frequency of testing, modality
      choice, and death. Conclusions: Use of a risk-based model of care has the
      potential to increase use of optimal treatments such as the use of home dialysis
      and preemptive kidney transplantation, while reducing costs and poor outcomes
      related to processes of care such as unnecessary laboratory testing; however,
      there is also potential for unintended consequences. Our mixed-methods approach
      will integrate perceptions and needs from key stakeholders (including patients
      with CKD, their families, and their providers) to guide implementation and ensure
      appropriate modifications.

PMID- 29375886
TI  - Evaluation of transcutaneous bilirubinometer (DRAEGER JM 103) use in Zimbabwean
      newborn babies.
AB  - Background: Acute Bilirubin Encephalopathy in the neonatal period is a major
      cause of permanent disability. Effective screening and surveillance are essential
      in the newborn period to enable timely management. Noninvasive transcutaneous
      bilirubin devices have been successfully used for screening in many settings. We
      evaluated the accuracy of the Draeger JM 103 (Medical Systems, USA) for
      estimating serum bilirubin in Zimbabwean newborns. Methods: Paired transcutaneous
      (forehead and sternum) and serum bilirubin measurements were compared on 283
      infants consecutively recruited between 01 August and 30 November 2015 at Harare
      Hospital Neonatal Unit. Using serum bilirubin as gold standard, Pearson
      Correlation Coefficient (r) was calculated for the two transcutaneous measurement
      sites. Linear regression plots of transcutaneous versus serum estimates were
      performed. Comparison was made between preterm and term babies. Specificity,
      sensitivity, positive predictive value and negative predictive value of the JM103
      were calculated including ROC curves to assess the accuracy of the diagnostic
      tests. Results: Fifty-five percent of the babies were male. Median gestational
      age was 38 weeks (range 28-42). One hundred and fifteen (41%) were preterm.
      Median postnatal age was 3 days (range 0-10). Serum bilirubin ranged 85-408
      MUmol/l, transcutaneous bilirubin sternum; 170-544 MUmol/l and forehead; 119-510
      MUmol/l. Correlation between serum and transcutaneous bilirubin (sternum) was
      0.77 and between serum and transcutaneous (forehead) was 0.72. Preterm babies
      correlation for sternum was 0.77 and forehead was 0.75. Term babies correlation
      for sternum was 0.76 and forehead was 0.70. The sensitivity for the sternum site
      was 76%, specificity 90%, Positive Predictive Value of 70 and Negative Predictive
      Value 92. Sensitivity for forehead site was 62%, specificity 95% with a Positive
      Predictive Value of 80 and Negative Predictive Value of 90. Bland-Altman plot of
      serum versus transcutaneous measurements showed agreement between the tests. The
      ROC curves showed that the accuracy of the two diagnostic tests were good with no
      significant difference between the two, p = 0.2954. Conclusion: The study
      demonstrated a strong positive correlation for both sternum and forehead sites
      with serum bilirubin in this Zimbabwean population of African origin. However,
      the sternum is a better site for identifying babies with jaundice compared to
      forehead. The Draeger JM-103 can be used to screening for neonatal jaundice in
      this population.

PMID- 29375887
TI  - A questionnaire survey of pharmacists regarding the clinical practice guidelines
      for the appropriate use of granulocyte-colony stimulating factors.
AB  - Background: Clinical practice guidelines should be user-friendly and confirming
      their penetration rate and compliance are critical. Methods: We conducted a
      nationwide web-based questionnaire survey among pharmacists regarding the 2013
      guidelines for the appropriate use of granulocyte-colony stimulating factors (G
      CSFs) (version 2, published by the Japan Society of Clinical Oncology [JSCO])
      between August 24 and September 6, 2015. Results: A total of 301 pharmacists
      responded; 96.0% belonged to hospitals and were board-certified pharmacists in
      oncology pharmacy (n = 133) and palliative pharmacy (n = 78). In addition, 61.5%
      of respondents (n = 185) worked for designated cancer care hospitals. The
      observation that 75.7% of respondents knew that the JSCO guidelines are available
      on the internet indicated that several pharmacists used this guideline. A high
      degree of usability by pharmacists was also demonstrated, as 98.0% and 51.5% of
      respondents, respectively, agreed with the statements "it is useful for the work
      of pharmacists" and "it is referred to in the actual work of pharmacists".
      However, more than half of the respondents (58.4%) agreed with the phrase "there
      are differences from the actual work of pharmacists". Conclusions: Their
      responses indicated that the respondents used the G-CSF guidelines and viewed
      them positively; however, the observation that about half of the respondents
      reported feeling that the guidelines do not match their current practice requires
      additional follow-up in future studies. The use of these guidelines should be
      routinely assessed in order to introduce novel cancer chemotherapy regimens and
      long-acting G-CSF in clinical practice.

PMID- 29375889
TI  - National estimates of self-reported sitting time in adults with multiple
      sclerosis.
AB  - Background: Limited data exist on the prevalence and distribution of sedentary
      behavior (SB) in multiple sclerosis (MS). Objective: The objective of this paper
      is to describe sitting time as a metric of SB in a large national sample of
      people with MS. Methods: A total of 8004 individuals from the North American
      Research Committee on MS (NARCOMS) Registry completed the sitting time question
      from the International Physical Activity Questionnaire in spring 2015. We present
      descriptive data on sitting time for the total sample and across
      sociodemographic, clinical, and behavioral characteristics. Results: The final
      sample included 6483 individuals. Of these, 36.7% were classified with mild
      disability, 24.7% with moderate disability, and 38.6% with severe disability.
      Median sitting time for the total sample was 480 min/day (P25 = 310 min/day, P75
      = 720 min/day). Sitting time was highest for individuals with MS who were male
      (540 min/day), not married (540 min/day), had a disease duration >30 years (540
      min/day), were underweight (540.5 min/day), had an annual income of < $15,000
      (585 min/day), presented with a progressive form of MS (600 min/day), were
      classified as insufficiently active (600 min/day), or presented with severe
      disability (661 min/day). Conclusion: Sitting time is twice as high in
      individuals with MS compared to the general population (240 min/day).

PMID- 29375888
TI  - Self-guided Change: The most common form of long-term, maintained health behavior
      change.
AB  - Millions of people change risky, health-related behaviors and maintain those
      changes. However, they often take years to change, and their unhealthy behaviors
      may harm themselves and others and constitute a significant cost to society. A
      review-similar in nature to a scoping review-was done of the literature related
      to long-term health behavior change in six areas: alcohol, cocaine and heroin
      misuse, gambling, smoking, and overeating. Based on the limited research
      available, reasons for change and strategies for changing and for maintaining
      change were also reviewed. Fifty years of research clearly indicate that as
      people age, in the case of alcohol, heroin and cocaine misuse, smoking, and
      gambling, 80-90 percent moderate or stop their unhealthy behaviors. The one
      exception is overeating; only 20 percent maintain their weight loss. Most of
      these changes, when they occur, appear to be the result of self-guided change.
      More ways to accelerate self-guided, health-related behavior change need to be
      developed and disseminated.

PMID- 29375890
TI  - Field evaluation of piglet vaccination with a Mycoplasma hyopneumoniae bacterin
      as compared to a ready-to-use product including porcine circovirus 2 and M.
      hyopneumoniae in a conventional French farrow-to-finish farm.
AB  - Background: A controlled randomized trial was performed on a well-managed
      conventional French 180-sow farm. The trial compared the growth performances of
      piglets vaccinated at weaning (single shot) either with a commercial monovalent
      Mycoplasma hyopneumoniae bacterin vaccine or with a commercial bivalent vaccine
      (Porcilis(r) PCV M Hyo) against M. hyopneumoniae and porcine circovirus 2 (PCV2).
      The farm's porcine reproductive and respiratory syndrome status was stable, and
      most diseases (enzootic pneumonia, atrophic rhinitis, post-weaning multisystemic
      wasting syndrome) were controlled by routine vaccination. Results: During the
      post-weaning phase, the growth performances of the piglets vaccinated with the
      bivalent vaccine were not significantly different from those vaccinated with the
      monovalent vaccine. However, during the fattening phase the group vaccinated with
      the bivalent vaccine had a significantly improved ADG (+34 g/d, p = 0. 047),
      resulting in a 5-day earlier shipment to slaughter. The group also had a shorter
      and lower PCV2 load in serum during the fattening period, and an improved lung
      lesions score. In both groups, three pigs died during the peak PCV2 viraemia (16
      23 weeks of age). Immunohistochemistry of the lymph nodes showed that in the
      group vaccinated with the bivalent vaccine, none of these pigs had PCV2-like
      lesions, while 2 out of the 3 from the other group did. Results suggest that the
      added PCV2 valence in the vaccination protocol helps countering the negative
      impact of subclinical PCV2 infection on growth. The calculated return on
      investment of the added PCV2 vaccine valence was ?1.7 extra revenue per
      slaughtered pig (? 39 additional revenue per sow and per year), despite the fact
      that the cost of the bivalent vaccine was higher than the monovalent M.
      hyopneumoniae vaccine. Conclusion: In this healthy conventional sow farm, the
      combined M. hyopneumoniae and PCV2 vaccination was efficacious, convenient to
      administer and profitable.

PMID- 29375891
TI  - Measuring skin necrosis in a randomised controlled feasibility trial of heat
      preconditioning on wound healing after reconstructive breast surgery: study
      protocol and statistical analysis plan for the PREHEAT trial.
AB  - Background: Essential strategies are needed to help reduce the number of post
      operative complications and associated costs for breast cancer patients
      undergoing reconstructive breast surgery. Evidence suggests that local heat
      preconditioning could help improve the provision of this procedure by reducing
      skin necrosis. Before testing the effectiveness of heat preconditioning in a
      definitive randomised controlled trial (RCT), we must first establish the best
      way to measure skin necrosis and estimate the event rate using this definition.
      Methods: PREHEAT is a single-blind randomised controlled feasibility trial
      comparing local heat preconditioning, using a hot water bottle, against standard
      care on skin necrosis among breast cancer patients undergoing reconstructive
      breast surgery. The primary objective of this study is to determine the best way
      to measure skin necrosis and to estimate the event rate using this definition in
      each trial arm. Secondary feasibility objectives include estimating recruitment
      and 30 day follow-up retention rates, levels of compliance with the heating
      protocol, length of stay in hospital and the rates of surgical versus
      conservative management of skin necrosis. The information from these objectives
      will inform the design of a larger definitive effectiveness and cost
      effectiveness RCT. Discussion: This article describes the PREHEAT trial protocol
      and detailed statistical analysis plan, which includes the pre-specified criteria
      and process for establishing the best way to measure necrosis. This study will
      provide the evidence needed to establish the best way to measure skin necrosis,
      to use as the primary outcome in a future RCT to definitively test the
      effectiveness of local heat preconditioning. The pre-specified statistical
      analysis plan, developed prior to unblinded data extraction, sets out the
      analysis strategy and a comparative framework to support a committee evaluation
      of skin necrosis measurements. It will increase the transparency of the data
      analysis for the PREHEAT trial. Trial registration: ISRCTN ISRCTN15744669.
      Registered 25 February 2015.

PMID- 29375892
TI  - Theory of porous catheters and their applications in intraparenchymal infusions.
AB  - Multiport catheters and catheters with a porous surface have been proposed for
      intraparenchymal infusions of therapeutics in fluid suspensions. Target diseases
      include brain cancer and serious neurodegenerative diseases, as well as
      peripheral tumors, for example in the prostate and the liver. We set up the
      theory for infusions from such devices, in particular the fluid flow equations
      which demand a coupling between the flow within the catheter and that in tissue.
      (Such a coupling is not necessary in the theory of infusion from single port
      catheters.) The new feature of such catheters, treated by our model, is revealed
      by infusions into inhomogeneous media. Multiport designs have the potential to
      overcome the limitation of single port catheters, for which the path of the fluid
      leaving the port is dominated by the inhomogeneities. We solve these equations
      for some simple cases to illustrate the key design features of porous catheters
      that show such advantages. The mathematics required for numerical solution with
      more realistic assumptions is also developed. We confirm the robustness of such
      catheters, when the ports are sufficiently resistive, against leakage paths that
      would compromise the infusions from catheters with one or a few large ports. The
      methods of this paper can be incorporated into a larger planning system for
      intraparenchymal infusions involving such devices.

PMID- 29375893
TI  - A comparative ultrasonographic evaluation of intrarenal artery resistive index
      among hypertensive and normotensive adults in a black African population compared
      to a European population.
AB  - Background: Hypertensive nephropathy is an important medical problem among the
      black African population. Early detection of renovascular changes using
      ultrasonography can provide opportunity for immediate intervention towards
      preventing or at least delaying the irreversible hypertensive nephropathy.
      Purpose: To compare intrarenal resistive index (RI) in healthy normotensive and
      hypertensive adults in Kano, Nigeria. Material and Methods: A prospective
      comparative study of intrarenal RI using ultrasound in 150 hypertensives and 150
      normotensive controls. The mean renal RI of the interlobar arteries of both
      kidneys were measured and recorded. The data were analyzed with the aid of
      computer-based SPSS 16.0 software for Windows. Results: The age range of the
      study participants was 35-70 years. The mean interlobar artery RI values were
      0.59 +/- 0.04 and 0.59 +/- 0.03 on the right and left sides, respectively, in
      normotensive control individuals while those of hypertensive individuals were
      0.73 +/- 0.03 and 0.73 +/- 0.03 for the mean interlobar artery RI values on the
      right and left sides, respectively. Conclusion: The intrarenal RIs were lower in
      normotensives when compared with the hypertensive participants, which were
      statistically significant. These showed that hypertension has significant effects
      on the kidneys, and with early detection and intervention, irreversible renal
      damage may be prevented.

PMID- 29375894
TI  - Screening-detected desmoid tumor of the breast: findings at conventional imaging
      and digital breast tomosynthesis.
AB  - Desmoid tumor of the breast is a rare benign entity that usually is mistaken for
      carcinoma clinically and radiologically. We report two cases of desmoid tumor of
      the breast detected by mammography screening using digital breast tomosynthesis
      (DBT). The larger tumor was detected at both full-field digital mammography
      (FFDM) and DBT. The smaller desmoid tumor, however, was identified only at
      tomosynthesis. Mammographic and ultrasonographic findings at diagnostic work-up
      were consistent with carcinoma of the breast. Preoperative needle biopsies could
      not conclusively diagnose the lesions. Both patients underwent excisional biopsy
      and histopathology revealed fibromatosis of the desmoid type.

PMID- 29375895
TI  - Progress in Remote Sensing of Photosynthetic Activity over the Amazon Basin.
AB  - Although quantifying the massive exchange of carbon that takes place over the
      Amazon Basin remains a challenge, progress is being made as the remote sensing
      community moves from using traditional, reflectance-based vegetation indices,
      such as the Normalized Difference Vegetation Index (NDVI), to the more functional
      Photochemical Reflectance Index (PRI). This new index, together with satellite
      derived estimates of canopy light interception and Sun-Induced Fluorescence
      (SIF), provide improved estimates of Gross Primary Production (GPP). This paper
      traces the development of these new approaches, compares the results of their
      analyses from multiple years of data acquired across the Amazon Basin and
      suggests further improvements in instrument design, data acquisition and
      processing. We demonstrated that our estimates of PRI are in generally good
      agreement with eddy-flux tower measurements of photosynthetic light use
      efficiency (epsilon) at four sites in the Amazon Basin: r2 values ranged from
      0.37 to 0.51 for northern flux sites and to 0.78 for southern flux sites. This is
      a significant advance over previous approaches seeking to establish a link
      between global-scale photosynthetic activity and remotely-sensed data. When
      combined with measurements of Sun-Induced Fluorescence (SIF), PRI provides
      realistic estimates of seasonal variation in photosynthesis over the Amazon that
      relate well to the wet and dry seasons. We anticipate that our findings will
      steer the development of improved approaches to estimate photosynthetic activity
      over the tropics.

PMID- 29375896
TI  - Ultrasound comparison of external and internal neck anatomy with the LMA Unique.
AB  - Introduction: Internal neck anatomy landmarks and their relation after placement
      of an extraglottic airway devices have not been studied extensively by the use of
      ultrasound. Based on our group experience with external landmarks as well as
      internal landmarks evaluation with other techniques, we aimed use ultrasound to
      analyze the internal neck anatomy landmarks and the related changes due to the
      placement of the Laryngeal Mask Airway Unique. Methods: Observational pilot
      investigation. Non-obese adult patients with no evidence of airway anomalies,
      were recruited. External neck landmarks were measured based on a validated and
      standardized method by tape. Eight internal anatomical landmarks, reciprocal by
      the investigational hypothesis to the external landmarks, were also measured by
      ultrasound guidance. The internal landmarks were re-measured after optimal
      placement and inflation of the extraglottic airway devices cuff Laryngeal Mask
      Airway Unique. Results: Six subjects were recruited. Ultrasound measurements of
      hyoid-mental distance, thyroid-cricoid distance, thyroid height, and thyroid
      width were found to be significantly (p < 0.05) overestimated using a tape
      measure. Sagittal neck landmark distances such as thyroid height, sternal-mental
      distance, and thyroid-cricoid distance significantly decreased after placement of
      the Laryngeal Mask Airway Unique. Conclusion: The laryngeal mask airway Unique
      resulted in significant changes in internal neck anatomy. The induced changes and
      respective specific internal neck anatomy landmarks could help to design devices
      that would modify their shape accordingly to areas of greatest displacement.
      Also, while external neck landmark measurements overestimate their respective
      internal neck landmarks, as we previously reported, the concordance of each
      measurement and their respective conversion factor could continue to be of help
      in sizing extraglottic airway devices. Due to the pilot nature of the study, more
      investigations are warranted.

PMID- 29375897
TI  - The importance of community screening of asymptomatic elderly for peripheral
      arterial disease by Doppler ultrasound and ankle-brachial index.
AB  - Background: Peripheral arterial disease is an atherosclerotic disease
      characterized by an increase in morbidity and mortality. For these reasons early
      diagnosis of peripheral arterial disease is important. Ankle-brachial systolic
      pressure index measurement is frequently used in screening studies. Evaluating
      waveforms of distal lower extremities with Doppler ultrasound can be used as a
      screening program and provides more accurate information on peripheral arterial
      disease. Aim: We investigate the prevalence of peripheral arterial disease,
      compare the efficacy of Doppler ultrasound evaluation of distal lower extremity
      waveforms and ankle-brachial systolic pressure index measurement in screening
      programs, and discuss the importance of early diagnosis of asymptomatic cases.
      Material and methods: A total of 457 patients over the age of 65 (between 65 and
      94, mean age: 71.4) including 270 males and 187 females were examined with
      Doppler ultrasound, had ankle-brachial systolic pressure index measurement taken
      and were screened for peripheral arterial disease. The correlation between
      Doppler ultrasound findings and ankle-brachial systolic pressure index was
      examined. Results: According to the Doppler ultrasound findings, in the
      aortoiliac (r = 0.648) and femoropopliteal (r = 0.564) area, there is a medium
      level of correlation between severe stenosis and occlusions and a low ankle
      brachial systolic pressure index value, and a low level of correlation between
      such abnormalities in the tibioperoneal region (r = 0.116) and a low ankle
      brachial systolic pressure index value. Therefore, while the sensitivity of ankle
      brachial systolic pressure index increases in proximal stenosis, it decreases in
      distal stenosis. Conclusion: Despite the fact that ankle-brachial systolic
      pressure index is a diagnostic test commonly used in screening studies,
      evaluation of distal arteries by means of Doppler ultrasound provides more
      accurate information in terms of the identification of peripheral arterial
      disease.

PMID- 29375898
TI  - A comparison of the ultrasound measurement of the inferior vena cava obtained
      with cardiac and convex transducers.
AB  - Background: Ultrasound measurement of the inferior vena cava diameter and its
      respiratory variability are amongst the predictors of fluid volume status. The
      primary purpose of the present study was to compare the consistency of inferior
      vena cava diameter measurements and the collapsibility index, obtained with
      convex and cardiac transducers. A secondary aim was to assess the agreement of
      the patient's allocation to one of the two groups: "fluid responder" or "fluid
      non-responder", based on inferior vena cava collapsibility index calculation made
      with two different probes. Methods: 20 experienced clinicians blinded to the
      purpose of the study analysed forty anonymized digital clips of images obtained
      during ultrasound examination of 20 patients. For each patient, one digital loop
      was recorded with a cardiac and the second with a convex probe. The participants
      were asked to determine the maximal and minimal diameters of the inferior vena
      cava in all presented films. An independent researcher performed a comparative
      analysis of the measurements conducted with both probes by all participants. The
      calculation of the collapsibility index and allocation to "fluid responder" or
      "fluid non-responder" group was performed at this stage of the study. Results:
      The comparison of measurements obtained with cardiac and convex probes showed no
      statistically significant differences in the measurements of the maximal and
      minimal dimensions and in the collapsibility index. We also noticed that the
      decision of allocation to the "fluid responder" or "non-responder" group was not
      probe-dependent. Conclusion: Both transducers can be used interchangeably for the
      estimation of the studied dimensions.

PMID- 29375899
TI  - High resolution ultrasonography of the tibial nerve in diabetic peripheral
      neuropathy.
AB  - Aim of the study: High-resolution ultrasonography of the tibial nerve is a fast
      and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study
      was aimed at finding out the correlation of the cross sectional area and maximum
      thickness of nerve fascicles of the tibial nerve with the presence and severity
      of diabetic peripheral neuropathy. Material and methods: 75 patients with type 2
      diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were
      analysed, and the severity of neuropathy was determined using the Toronto
      Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of
      diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as
      controls. The cross sectional area and maximum thickness of nerve fascicles of
      the tibial nerves were calculated 3 cm cranial to the medial malleolus in both
      lower limbs. Results: The mean cross sectional area (22.63 +/- 2.66 mm2) and
      maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients
      with diabetic peripheral neuropathy compared with both control groups was
      significantly larger, and statistically significant correlation was found with
      the Toronto Clinical Neuropathy Score (p < 0.001). The diabetic patients with no
      signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/-
      1.72 mm2) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm)
      than healthy non-diabetic subjects (12.42 +/- 1.01 mm2 and 0.30 mm respectively).
      Conclusion: The cross sectional area and maximum thickness of nerve fascicles of
      the tibial nerve is larger in diabetic patients with or without peripheral
      neuropathy than in healthy control subjects, and ultrasonography can be used as a
      good screening tool in these patients.

PMID- 29375900
TI  - Uterine artery Doppler velocimetry in hypertensive disorder of pregnancy in
      Nigeria.
AB  - Aim of the study: To evaluate the value of uterine artery Doppler indices and
      waveform pattern in predicting fetuses at risk for intrauterine growth
      restriction in hypertensive disorders of pregnancy. Materials and methods: This
      was a prospective cross-sectional study including 80 pregnant subjects with
      hypertensive disorders of pregnancy and two control groups. Uterine artery
      Doppler sonography was performed in all study participants. Uterine artery
      Doppler indices across the groups were compared using the analysis of variance
      (ANOVA) while the presence of prediastolic notch was analyzed with the Chi Square
      test. Results: For the hypertensive disorders of pregnancy group, resistivity
      index > 0.66 had a sensitivity of 50.0%, specificity of 69.1% and a positive
      predictive value of 22.2% for predicting intrauterine growth restriction. The
      odds ratio was 2.2 with a 95% confidence interval of 0.6-7.8. The presence of
      prediastolic notching had a sensitivity of 100.0%, specificity of 96.0% and a
      positive predictive value of 80.0% for predicting intrauterine growth
      restriction. The odds ratio was 22.7 with a 95% confidence interval of 7.5-68.5.
      Conclusion: Uterine artery Doppler sonography is useful for predicting fetuses at
      risk for intrauterine growth restriction in hypertensive disorder of pregnancy.
      Prediastolic notching is more sensitive and more specific than uterine artery
      resistivity index in predicting fetuses at risk of intrauterine growth
      restriction in established hypertensive disorder of pregnancy.

PMID- 29375901
TI  - Conjoined twins - role of imaging and recent advances.
AB  - Introduction: Conjoined twins are identical twins with fused bodies, joined in
      utero. They are rare complications of monochorionic twinning. The purpose of this
      study is to describe the various types of conjoined twins, the role of imaging
      and recent advances aiding in their management. Material and methods: This was a
      twin institutional study involving 3 cases of conjoined twins diagnosed over a
      period of 6 years from 2010 to 2015. All the 3 cases were identified antenatally
      by ultrasound. Only one case was further evaluated by MRI. Results: Three cases
      of conjoined twins (cephalopagus, thoracopagus and omphalopagus) were accurately
      diagnosed on antenatal ultrasound. After detailed counseling of the parents and
      obtaining written consent, all the three cases of pregnancy were terminated.
      Delivery of the viable conjoined twins was achieved without any complications to
      the mothers, and all the three conjoined twins died after a few minutes.
      Conclusion: Ultrasound enables an early and accurate diagnosis of conjoined
      twins, which is vital for obstetric management. MRI is reserved for better tissue
      characterization. Termination of pregnancy when opted, should be done at an early
      stage as later stages are fraught with problems. Recent advances, such as 3D
      printing, may aid in surgical pre-planning, thereby enabling successful surgical
      separation of conjoined twins.

PMID- 29375902
TI  - Fine-needle versus core-needle biopsy - which one to choose in preoperative
      assessment of focal lesions in the breasts? Literature review.
AB  - Aim: The aim of the study was to review two techniques that can be used to verify
      focal lesions in the breasts: fine-needle aspiration biopsy and core-needle
      biopsy. Material and methods: Fifty-five articles (original papers and reviews),
      half of them published within the past 5 years, were included in the analysis.
      The authors also took their own experience into account. Results: Pre-operative
      assessment of focal lesions in the breasts is crucial in the planning of further
      therapeutic management. The role of fine-needle aspiration biopsy has been
      reduced lately due to its low sensitivity and specificity as well as a high rate
      of non-diagnostic, suspicious and false negative results. This method does not
      enable one to differentiate between in situ and invasive disease. Currently, fine
      needle biopsy is recommended for cystic lesions, suspected of being recurrences
      in the chest wall, and lymph node metastases. Core-needle biopsy is the basic
      diagnostic method of breast lesions. According to the recommendations of the
      Polish Ultrasound Society and American College of Radiology, BIRADS 4 and 5
      lesions should be evaluated histopathologically. Core-needle biopsy makes it
      possible to establish a final diagnosis more frequently than fine-needle biopsy,
      both in the case of benign and malignant lesions. It delivers more information
      about the nature of a tumor (mutation of HER-2, estrogen and progesterone
      receptors and Ki-67 index). Its limitations include: underestimation of invasion
      and failure to recognize the components of ductal carcinoma in situ in papillary
      and atypical lesions. Single fine-needle aspiration biopsy is inexpensive, but
      when considering the cost of further diagnosis due to non-diagnostic, suspicious
      and atypical results, this method generates high additional costs. Conclusions:
      Microscopic verification of focal breast lesions is crucial for further
      therapeutic decisions. It has been proven that histopathological verification is
      more accurate and has more advantages than cytological assessment.

PMID- 29375903
TI  - Chest wall - underappreciated structure in sonography. Part II: Non-cancerous
      lesions.
AB  - The chest wall is a vast and complex structure, hence the wide range of
      pathological conditions that may affect it. The aim of this publication is to
      discuss the usefulness of ultrasound for the diagnosis of benign lesions
      involving the thoracic wall. The most commonly encountered conditions include
      sternal and costal injuries and thoracic lymphadenopathy. Ultrasound is very
      efficient in identifying the etiology of pain experienced in the anterior chest
      wall following CPR interventions. Both available literature and the authors' own
      experience prompt us to propose ultrasound evaluation as the first step in the
      diagnostic workup of chest trauma, as it permits far superior visualization of
      the examined structures compared with conventional radiography. Sonographic
      evaluation allows correct diagnosis in the case of various costal and chondral
      defects suspicious for cancer. It also facilitates diagnosis of such conditions
      as degenerative lesions, subluxation of sternoclavicular joints (SCJs) and
      inflammatory lesions of various etiology and location. US may be used as the
      diagnostic modality of choice in conditions following thoracoscopy or
      thoracotomy. It may also visualize the fairly common sternal wound infection,
      including bone inflammation. Slipping rib syndrome, relatively little known among
      clinicians, has also been discussed in the study. A whole gamut of benign lesions
      of thoracic soft tissues, such as enlarged lymph nodes, torn muscles, hematomas,
      abscesses, fissures, scars or foreign bodies, are all easily identified on
      ultrasound, just like in other superficially located organs.

PMID- 29375904
TI  - Chest wall - a structure underestimated in ultrasonography. Part III: Neoplastic
      lesions.
AB  - Chest wall neoplasms mainly include malignancies, metastatic in particular.
      Differential diagnosis should include clinical data; tumor location, extent,
      delineation; the degree of homogeneity; the presence of calcifications; the
      nature of bone destruction and the degree of vascularization. The aim of the
      paper is to present both the benefits and limitations of ultrasound for the
      diagnosis of chest wall neoplasms. The neoplastic process may be limited to the
      chest wall; it may spread from the chest wall into the intrathoracic structures
      or spread from the inside of the chest towards the chest wall. Benign tumors
      basically originate from vessels, nerves, bones, cartilage and soft tissues. In
      this paper, we briefly discuss malformations of blood and lymphatic vessels,
      glomus tumor as well as neurogenic tumors originating in the thoracic branches of
      the spinal nerves and the autonomic visceral system. Metastases, particularly
      lung, breast, kidney cancer, melanoma and prostate cancer, are predominant tumors
      of the osteocartilaginous structures of the chest wall. Plasma cell myeloma is
      also relatively common. The vast majority of these lesions are osteolytic, which
      is reflected in ultrasound as irregular cortical defects. Osteoblastic foci
      result only in irregular outline of the bone surface. Lipomas are the most common
      neoplasms of the chest wall soft tissue. Elastofibroma is another tumor with
      characteristic echostructure. Desmoid fibromatosis, which is considered to be a
      benign lesion with local aggressivity and recurrences after surgical resection,
      represents an interesting tumor form the clinical point of view. Ultrasonography
      represents an optimal tool for the monitoring of different biopsies of
      pathological lesions located in the chest wall. Based on our experiences and
      literature data, this method should be considered as a preliminary diagnosis of
      patients with chest wall tumors.

PMID- 29375905
TI  - Double-chambered right ventricle in a 16-year-old patient with Williams syndrome.
AB  - We present a case of double-chambered right ventricle diagnosed during
      preparation for colonoscopy due to gastrointestinal bleeding in a 16-year-old,
      mentally disabled boy with Williams syndrome. The patient was previously
      diagnosed with ventricular septal defect and mild pulmonary stenosis.
      Echocardiography performed under general anesthesia revealed hypertrophied
      muscular bundles in the right ventricle with the maximum gradient of 100 mmHg,
      causing severe outflow obstruction. This type of defect is extremely rare in
      patients with Williams syndrome, with only one case, which was diagnosed during
      invasive angiocardiography, described in world literature. A successful total
      surgical correction was performed based on echocardiography data.

PMID- 29375906
TI  - Fetal ultrasound: Early diagnosis and natural evolution of proximal femoral focal
      deficiency.
AB  - Proximal femoral focal deficiency is an extremely rare congenital anomaly with
      only a few case reports in the literature. This case illustrates one diagnosed by
      prenatal ultrasound. The diagnosis may be isolated or associated with other
      abnormalities and syndromes. This report describes the early obstetrical
      ultrasound diagnosis, its evolution and associated findings throughout pregnancy.
      To the best of our knowledge, it is the first report associating this diagnosis
      with sickle cell trait. Another finding in our patient was a concomitant
      intrauterine growth restriction that we attribute to placental infarctions and a
      retro placental hemorrhage, also on the basis of sickle cell trait. At birth,
      placental weight was under the 10th percentile for gestational age. Obstetrical
      ultrasound in the prenatal diagnosis of proximal femoral focal deficiency is
      important, because early recognition of this malformation could provide useful
      information to parents and physicians regarding newborn management and
      therapeutic planning.

PMID- 29375907
TI  - A twin pregnancy with a hydatidiform mole and a coexisting live fetus: prenatal
      diagnosis, treatment, and follow-up.
AB  - Twin molar pregnancy with a hydatidiform mole and a coexisting live fetus is a
      rare form of gestational trophoblastic disease associated with an increased risk
      of obstetric complications and poor perinatal outcome. Prenatal diagnosis is
      essential for couple counseling and follow-up in Tertiary Reference Centers.
      Magnetic resonance imaging is important for the diagnostic differentiation of
      placental mesenchymal dysplasia and exclusion of myometrial invasion. Here we
      present a case of twin molar pregnancy with a hydatidiform mole and a coexisting
      live fetus diagnosed at gestational week 14 using two-dimensional (2D) and three
      dimensional (3D) ultrasound and magnetic resonance imaging. We also describe the
      obstetric management and postmolar follow-up.

PMID- 29375908
TI  - Comparison of Repeatability and Agreement between Swept-Source Optical Biometry
      and Dual-Scheimpflug Topography.
AB  - Purpose: To assess the repeatability and agreement of parameters obtained with
      two biometers and to compare the predictability. Methods: Biometry was performed
      on 101 eyes with cataract using the IOLMaster 700 and the Galilei G6. Three
      measurements were obtained per eye with each device, and repeatability was
      evaluated. The axial length (AL), anterior chamber depth (ACD), keratometry (K),
      white-to-white (WTW) corneal diameter, central corneal thickness (CCT), and lens
      thickness (LT) were measured and postoperative predictability was compared.
      Results: Measurements could not be obtained with the IOLMaster 700 in one eye and
      in seven eyes with the Galilei G6 due to dense cataract. Both the IOLMaster 700
      and Galilei G6 showed good repeatability, although the IOLMaster 700 showed
      better repeatability than the Galilei G6. There were no statistically significant
      differences in AL, ACD, steepest K, WTW, and LT (P > 0.050), although flattest K,
      mean K, and CCT differed (P < 0.050). The proportion of eyes with an absolute
      prediction error within 0.5 D was 85.0% for the IOLMaster 700 and was 80.0% for
      the Galilei G6 based on the SRK/T formula. Conclusions: Two biometers showed high
      repeatability and relatively good agreements. The swept-source optical biometer
      demonstrated better repeatability, penetration, and an overall lower prediction
      error.

PMID- 29375909
TI  - Psychological Distress in Patients with Symptomatic Vitreous Floaters.
AB  - Purpose: To evaluate the degree of psychological distress in symptomatic vitreous
      floater patients and to evaluate whether these psychological factors are
      associated with the severity of discomfort associated with vitreous floaters.
      Methods: We recruited 61 patients with symptomatic vitreous floaters and 34
      controls. The degree of posterior vitreous detachment (PVD) was evaluated using
      optical coherence tomography. We measured the level of depression, perceived
      stress, state, and trait anxiety and the degree of floater-associated discomfort
      with self-administered questionnaire. We compared psychological parameters
      between floater patients and control. We also compared clinical and psychological
      characteristics among different floater-associated discomfort severity groups.
      Results: Symptomatic vitreous floater patients showed higher rate of complete PVD
      and higher psychological distress compared to the control. On multiple logistic
      regression analysis, complete PVD (p = 0.001), depression (p = 0.001), and
      younger age (p = 0.037) were significantly associated with symptomatic floaters.
      There were no significant differences in complete PVD rate among different
      discomfort groups, while severe discomfort group showed higher depression,
      perceived stress, and state and trait anxiety compared to the other two milder
      symptom groups. Conclusions: Symptomatic vitreous floater patients showed
      substantial level of psychological distress, and the severity of floater symptoms
      was significantly associated with psychological distress.

PMID- 29375910
TI  - Optic Neuritis in the Older Chinese Population: A 5-Year Follow-Up Study.
AB  - Objective: This study aims to describe the clinical manifestations and outcomes
      in a cohort of older Chinese patients. Method: A retrospective study of patients
      aged >= 45 years who had a first episode of optic neuritis (ON) between May 2008
      and November 2012. Clinical features at onset and last follow-up were analyzed
      within subgroups (age 45-65 years and age >= 65 years). Results: 76 patients (99
      eyes) were included, of which 58% were females. The mean age at presentation was
      55.53 +/- 8.29 years (range: 45-83 years). Vision loss was severe at
      presentation, with initial best corrected vision activity (BCVA) < 20/200 in 93%
      and final BCVA < 20/200 in 53% of patients at 5-year follow-up. Final BCVA
      significantly correlated with the initial BCVA and peripapillary retinal nerve
      fiber layer. At last follow-up, 14.5% were diagnosed with neuromyelitis optica
      spectrum disorder (NMOSD), 1.3% were diagnosed with multiple sclerosis (MS), 5.2%
      with chronic relapsing inflammatory optic neuropathy, 1.3% with infectious ON,
      and 19.7% with autoimmune ON. None of the elderly group (>=65 years) developed
      NMOSD or MS. Conclusion: Chinese patients in the age group >= 65 years with ON
      are less likely to develop NMOSD or MS. Notwithstanding, they had more severe
      visual loss at onset and poor recovery.

PMID- 29375911
TI  - Multimodality Imaging Assessment of Ocular Ischemic Syndrome.
AB  - Objectives: To assess the underlying mechanisms of OIS and confirm the
      haemodynamic and retinal structure changes of early OIS. Methods: An
      observational cross-sectional study was conducted of 60 internal carotid artery
      (ICA) stenosis patients, and they were divided into OIS and control group. Colour
      doppler imaging, optical coherence tomography, and fundus fluorescein angiography
      were performed. Results: The middle cerebral artery (MCA) stenosis differs
      significantly between the two groups. More OIS patients had new collateral
      patency of posterior communicating artery (PCoA) and retrograde flow via the
      ophthalmic artery (OA) (p < 0.001). The peak systolic velocity (PSV) in central
      retinal artery (CRA) and choroidal thickness (CT) was significantly reduced in
      OIS patients (p = 0.001 and p < 0.001). The arm-retina time (ART) and the retinal
      arteriovenous passage time (AVP) were prolonged in OIS patients (p < 0.001 and p
      = 0.001). CT, ART, and PSV of the CRA showed high sensitivity, while ART and ICA
      stenosis grade showed high specificity for the diagnosis of OIS according to ROC
      curve. Conclusions: Patients who suffered from severe ipsilateral ICA stenosis,
      new collateral patency of PCoAs, and MCA stenosis may be more susceptible to OIS.
      The most sensitive sign is PSV of CRA and CT, and the most specific sign is ART.

PMID- 29375912
TI  - Predictors of Insulin Resistance in Children versus Adolescents with Obesity.
AB  - Introduction: Obesity is a risk factor to develop metabolic syndrome (MetS) and
      type 2 diabetes mellitus (T2DM). Insulin resistance (IR) plays a major part in
      both. With increasing incidence of childhood obesity, this retrospective study
      aimed to identify predictors of IR in children/adolescents with obesity to
      optimize screening for IR. Method: Patients aged >= 2-<= 18 years with obesity
      (BMI-SDS > 2.3) were included. IR was defined as HOMA-IR >= 3.4, and MetS if >=3
      of the following criteria were present: waist circumference and blood pressure >=
      95th age percentile, triglycerides >= 1.7 mmol/l, HDL < 1.03 mmol/l, and fasting
      plasma glucose >= 5.6 mmol/l. Results: In total, 777 patients were included. Of
      the 306 children, 51, 38, and 0 were diagnosed with IR, MetS, and T2DM,
      respectively. Of the 471 adolescents, 223, 95, and 0 were diagnosed with IR,
      MetS, and T2DM, respectively. In the multivariable regression model, BMI-SDS,
      preterm birth, and Tanner stage were associated with IR in children (6.3 (95% CI
      1.3-31.1), 5.4 (95% CI 1.4-20.5), 2.2 (95% CI 1.0-4.8)), and BMI-SDS and waist
      circumference in adolescents (4.0 (95% CI 1.7-9.2), 3.7 (95% CI 1.5-9.4)).
      Conclusion: Different IR predictors were observed in children/adolescents with
      obesity. These predictors can be used to optimize screening for IR in pediatric
      populations.

PMID- 29375913
TI  - Seizure-Related Injuries among People with Epilepsy at the Outpatient Department
      of the University of Gondar Hospital, Northwest Ethiopia: Cross-Sectional
      Institutional-Based Study.
AB  - Background: The characteristics of epilepsy such as the episodic nature of
      impairment of consciousness and motor control, psychomotor comorbidity, seizure
      frequency, and side effects of antiepileptic drugs impact negatively on the
      physical safety of the patients. Physical injuries such as burn, fracture, dental
      loss, and hemorrhage affect the quality of patients' life to the extent of death.
      Thus, the main purpose of this study was to assess the prevalence of physical
      injury and associated factors among people with epilepsy. Methods: The study was
      carried out among 409 people with epilepsy. Cross-sectional study design was
      utilized to enroll the selected study participants using systematic random
      sampling technique. Binary and multivariable logistic regression were fitted to
      identify associated factors using an odds ratio and 95% CI. Results: The overall
      estimated prevalence of seizure-related physical injury was found to be 27.9%. Of
      the 27.9% seizure-related physical injuries, 12.5% had abrasions, 5.9% had burns,
      4.4% had dental injuries, 2.2% had fractures, and 1.5% had head injuries and
      dislocations, respectively. Employment, 2-3 years duration of illness, seizure
      frequencies, and frequencies of drug taken were factors associated with physical
      injury. Conclusion: More than a quarter of the study participants experienced
      physical injury. Designing/strengthening injury prevention strategies is
      suggested especially for those who had uncontrolled seizure frequency for longer
      period of time.

PMID- 29375914
TI  - Longitudinal Brain Functional Connectivity Changes of the Cortical Motor-Related
      Network in Subcortical Stroke Patients with Acupuncture Treatment.
AB  - In clinical practice, the effectiveness of the rehabilitation therapy such as
      acupuncture combining conventional Western medicine (AG) on stroke people's motor
      related brain network and their behaviors has not been systematically studied. In
      the present study, seventeen adult ischemic patients were collected and divided
      into two groups: the conventional Western medicine treatment group (CG) and the
      AG. The neurological deficit scores (NDS) and resting-state functional MRI data
      were collected before and after treatment. Compared with the CG patients, AG
      patients exhibited a significant enhancement of the percent changes of NDS from
      pre- to posttreatment intervention. All patients showed significant changes of
      functional connectivity (FC) between the pair of cortical motor-related regions.
      After treatment, both patient groups showed a recovery of brain connectivity to
      the nearly normal level compared with the controls in these pairs. Moreover, a
      significant correlation between the percent changes of NDS and the pretreatment
      FC values of bilateral primary motor cortex (M1) in all patients was found. In
      conclusion, our results showed that AG therapy can be an effective means for
      ischemic stroke patients to recover their motor function ability. The FC
      strengths between bilateral M1 of stroke patients can predict stroke patients'
      treatment outcome after rehabilitation therapy.

PMID- 29375915
TI  - Transcutaneous Vagus Nerve Stimulation Combined with Robotic Rehabilitation
      Improves Upper Limb Function after Stroke.
AB  - The efficacy of standard rehabilitative therapy for improving upper limb
      functions after stroke is limited; thus, alternative strategies are needed. Vagus
      nerve stimulation (VNS) paired with rehabilitation is a promising approach, but
      the invasiveness of this technique limits its clinical application. Recently, a
      noninvasive method to stimulate vagus nerve has been developed. The aim of the
      present study was to explore whether noninvasive VNS combined with robotic
      rehabilitation can enhance upper limb functionality in chronic stroke. Safety and
      efficacy of this combination have been assessed within a proof-of-principle,
      double-blind, semirandomized, sham-controlled trial. Fourteen patients with
      either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted
      therapy associated with real or sham VNS, delivered for 10 working days. Efficacy
      was evaluated by change in upper extremity Fugl-Meyer score. After intervention,
      there were no adverse events and Fugl-Meyer scores were significantly better in
      the real group compared to the sham group. Our pilot study confirms that VNS is
      feasible in stroke patients and can produce a slight clinical improvement in
      association to robotic rehabilitation. Compared to traditional stimulation,
      noninvasive VNS seems to be safer and more tolerable. Further studies are needed
      to confirm the efficacy of this innovative approach.

PMID- 29375916
TI  - Late Emergence of an Imatinib-Resistant ABL1 Kinase Domain Mutation in a Patient
      with Chronic Myeloid Leukemia.
AB  - The introduction of the tyrosine kinase inhibitor (TKI) imatinib has
      revolutionised the outlook of chronic myeloid leukemia (CML); however, a
      significant proportion of patients develop resistance through several mechanisms,
      of which acquisition of ABL1 kinase domain mutations is prevalent. In chronic
      phase patients, these mutations become evident early in the disease course. A
      case is described of a chronic-phase CML patient who achieved a sustained, deep
      molecular response but who developed an Y253H ABL1 kinase domain mutation nearly
      nine years after commencing imatinib. Switching therapy to bosutinib resulted in
      a rapid reachievement of a major molecular response. Long-term TKI treatment
      impacts on quality of life and late losses of responses are usually due to lack
      of adherence. This case highlights the requirement for ABL1 kinase domain
      mutation analysis in those CML patients on long-term imatinib who lost their
      molecular response, regardless of whether nonadherence is suspected.

PMID- 29375917
TI  - Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed
      Anemia due to Ribavirin.
AB  - Interferon (IFN) and ribavirin (RBV) combination therapy was previously the
      standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection.
      But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved
      for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more
      effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year
      old woman with chronic HCV genotype 2b infection. She received five treatments
      including RBV and IFN therapy before SOF was approved and all of them were
      ineffective. Therapies that included RBV induced severe anemia and led to
      discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change
      in hemoglobin (Hb) from baseline was -3.7 g/dL. However, SOF/RBV therapy was
      effective and she achieved sustained virologic response (SVR) with a maximum
      change in Hb from baseline of only -1.2 g/dL. We also found reticulocyte count
      was very low during treatment in this case and speculate it was one of the
      reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV
      therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen
      is safe and effective for patients who have or are at risk of anemia induced by
      RBV.

PMID- 29375918
TI  - Staphylococcus aureus Bacteremia Complicated by Psoas Abscess and Infective
      Endocarditis in a Patient with Atopic Dermatitis.
AB  - The close relationship between atopic dermatitis (AD) and infective endocarditis
      (IE) has been implicated. Staphylococcus aureus colonization is frequently seen
      observed in AD patients' skin lesions. Although a case of IE due to S. aureus
      bacteremia in an AD patient has been sporadically reported, a case of S. aureus
      bacteremia complicated by psoas abscess and IE has not been previously reported.
      A 42-year-old man with a history of AD presented to our hospital complaining of
      fever, fatigue, chills, lower right back pain, and poor appetite for a week. His
      blood cultures showed growth of S. aureus. On day 3, the patient presented acute
      cardiac failure and was diagnosed with IE based on echocardiogram examination.
      Since the patient's cardiac failure did not respond to medication, an emergency
      surgery was performed on the fourth day of hospitalization. The patient underwent
      successful surgical treatment of the heart lesions and subsequent percutaneous
      drainage of psoas abscess and received intensive antibiotics, which successfully
      improved his condition. Our report emphasizes awareness of the association
      between AD and invasive S. aureus infections.

PMID- 29375919
TI  - A Case of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Pregnancy
      Treated with Garenoxacin.
AB  - Pneumonia in pregnancy is associated with adverse maternal and foetal outcomes,
      and intensive treatment with appropriate antibiotics is essential. However, cases
      caused by pathogens that are resistant to antibiotics suitable for the developing
      foetus are challenging. We herein report a case of macrolide-refractory
      Mycoplasma pneumoniae pneumonia in pregnancy. A 40-year-old multigravida with
      twin pregnancy complained of cough and fever at 13 weeks of gestation and was
      diagnosed with pneumonia. Even though empiric treatment with ceftriaxone and oral
      azithromycin was started, her condition deteriorated rapidly. The findings of
      chest computed tomography suggested Mycoplasma pneumoniae pneumonia. Since
      azithromycin did not work, this strain was considered to be macrolide-refractory.
      Garenoxacin, an oral quinolone, was selected and was dramatically effective. The
      use of quinolone could be justified with the emergence of drug-resistant
      bacterial/atypical pneumonia and in the maternal life-threatening condition.

PMID- 29375920
TI  - Profound Sinoatrial Arrest Associated with Ibrutinib.
AB  - Background: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor approved for
      second-line treatment for mantle cell lymphoma (MCL), chronic lymphocytic
      leukemia (CLL), and Waldenstrom macroglobulinemia. Ibrutinib use has been linked
      to increased incidence of atrial fibrillation and hypertension in multiple
      studies. Other forms of cardiac toxicities have also been reported in isolated
      case reports. Bradycardia and asystole have not been associated with ibrutinib
      use in the past. Case Report: We present a case of a 76-year-old female with no
      prior cardiac history, who initiated treatment with ibrutinib for relapsing
      mantle cell lymphoma and was noted to have symptomatic bradycardia, greater than
      20 second long pauses on her cardiac monitor requiring placement of a permanent
      pacemaker. Conclusion: This is the first case associating bradycardia and
      asystole with tyrosine kinase inhibitor use. Irreversible inhibition of certain
      cardioprotective tyrosine kinases has been a growing topic of research in
      oncology therapeutics.

PMID- 29375921
TI  - Minimally Invasive Endoscopic Approach to the Cervicothoracic Junction for
      Vertebral Osteomyelitis.
AB  - The selection of an anterior, lateral, or posterior approach to the
      cervicothoracic junction for surgical treatment of vertebral osteomyelitis is
      still a matter of debate. These ordinary approaches generally require an
      extensile exposure. This article describes a less invasive approach case of a
      vertebral osteomyelitis of T2/3 using a video-assisted operating technique of
      thoracic surgery (VATS). A 78-year-old female underwent anterior debridement and
      interbody fusion with bone graft at T2/3 using a lateral surgical approach
      through a right thoracotomy with VATS. The VATS through two small skin incisions
      in the axillary region provides a good view without requiring elevation of the
      scapula with extensile muscle dissection and rib resection. There was no
      complication without partial lobectomy due to pleural adhesion during the
      perioperative period. Currently, at 1 year after operation, the patient has no
      back pain with neurologically normal findings and no inflammation findings (CRP
      was 0.01 mg/dl). Although the operating field of the upper thoracic level in the
      lateral approach is generally deep and narrow, the VATS provides a good view and
      allows us to perform adequate debridement and bone fusion at the T2/3 level with
      a less invasive approach than those previously described anterior or laterally or
      posterior approach.

PMID- 29375922
TI  - Angioleiomyoma of the Auricle: An Unusual Tumor on a Rare Location.
AB  - Cutaneous angioleiomyomas (ALMs) (also known as vascular leiomyomas or
      angiomyomas) are unusual benign tumors of the skin deriving from the muscle layer
      of dermal blood vessels. They usually manifest as tender subcutaneous nodules,
      mostly encountered on the legs of adult women in their fifth or sixth life
      decade. ALMs rarely develop on the head/neck area, and even more rarely (<3% of
      all cases) on the auricle. Head/neck (including ear) ALMs differ from their more
      usual leg counterparts in that they are usually painless and do not show a female
      predominance. The diagnosis is clinically difficult, and most cases are diagnosed
      by histopathologic examination. A new case of an auricular ALM in a 40-year-old
      Caucasian man is reported herein, and a brief literature review on this unusual
      tumor is presented.

PMID- 29375923
TI  - Autoamputation of Genitalia in Bipolar Patient.
AB  - According to literature, genital self-mutilation (GSM) is more commonly
      associated with psychosis as compared with self-mutilation as a whole. There have
      been many case reports of GSM in psychotic disorders. We describe herein a case
      of a Caucasian, employed, and married male suffering from bipolar disorder type
      II with history of self-mutilating behavior, who amputated his penis during
      symptom-free phase of his illness. Several features are reflected as risky
      elements for genital self-mutilation, for example, homosexual and transsexual
      tendencies, abandonment of the male genitals, lack of competent male for
      identification during childhood, feeling of guilt for sexual offences, and self
      injuries in anamnesis. This report will highlight various factors responsible for
      self-mutilation in nonpsychotic and nondelusional person.

PMID- 29375924
TI  - Primary Signet-Ring Cell Adenocarcinoma of the Urinary Bladder Treated with
      Partial Cystectomy: A Case Report and Review of the Literature.
AB  - Primary signet-ring cell carcinoma is a variant of adenocarcinoma which is
      extremely rare, associated with poor prognosis and generally found to be
      resistant to chemotherapy and radiotherapy. We report a case of primary signet
      ring cell carcinoma of the bladder which was successfully treated with partial
      cystectomy. A 71-year-old female with a history of type 2 diabetes, hypertension,
      and ischaemic heart disease presented with painless haematuria for 2 months'
      duration. The abdominal ultrasonography showed a localised polypoidal vesical
      growth arising from the bladder dome. Cystoscopy revealed an exophytic solid
      tumour in the anterior fundal wall. A deep transurethral resection of bladder
      tumour was done and histology revealed an adenocarcinoma composed of mucinous and
      signet-ring cell components. Later, considering the patient's age and the poor
      general condition, a partial cystectomy was done. Follow-up cystoscopy and
      ultrasonography were done at 12 months and there was no evidence of tumour
      recurrence and the patient is currently symptom-free. Partial cystectomy may be
      considered in patients with localised tumour without evidence of metastasis and
      poor general condition. Regular cystoscopies and ultrasound imaging are necessary
      for follow-up and early identification of recurrences.

PMID- 29375925
TI  - Men's Responses to Women's Sexual Refusals: Development and Construct Validity of
      a Virtual Dating Simulation of Sexual Aggression.
AB  - Objective: To provide evidence regarding the construct validity of a sexual
      aggression proxy in which male participants go on multiple virtual dates with a
      woman. A unique strength of this proxy is participants' opportunity to make
      choices throughout the simulation about how they interact with their virtual
      date. These decisions determine their exposure to the female agent's sexual
      refusals. Method: Piloting included focus groups (n = 82), surveys (n = 95), and
      cognitive interviews (n = 32). To establish construct validity, 87 male
      participants completed two separate sessions: 1) an online survey with measures
      of discriminant and convergent validity; and 2) a lab session in which they went
      on multiple dates that included nonsexual options, sexual options which the
      female agent accepted, and sexual options she refused. Sexual aggression was
      operationalized as the total number of sexual refusals that participants'
      received. Results: There was strong correlational evidence for discriminant and
      convergent validity. As hypothesized, there were some differences in the risk
      factors associated with refusals received on casual as compared to steady dates.
      Additionally, the number of refusals received was associated with the types of
      thoughts and actions commonly reported by perpetrators. Conclusions: This
      simulation provides a new approach for examining sexual aggression in controlled
      experiments that vary factors within the simulation such as the man's and woman's
      intoxication and past sexual history. Because what happens is based on each
      individual's responses, it could be adapted for use in prevention and treatment
      programs.

PMID- 29375926
TI  - Design and Control of Motion Compensation Cardiac Catheters.
AB  - Robotic cardiac catheters have the potential to revolutionize heart surgery by
      extending minimally invasive techniques to complex surgical repairs inside the
      heart. However, catheter technologies are currently unable to track fast tissue
      motion, which is required to perform delicate procedures inside a beating heart.
      This paper proposes an actuated catheter tool that compensates for the motion of
      heart structures like the mitral valve apparatus by servoing a catheter guidewire
      inside a flexible sheath. We examine design and operation parameters that affect
      performance and establish that friction and backlash limit the tracking
      performance of the catheter system. Based on the results of these experiments and
      a model of the backlash behavior, we propose and implement compensation methods
      to improve trajectory tracking performance. The catheter system is evaluated with
      3D ultrasound guidance in simulate in vivo conditions. The results demonstrate
      that with mechanical and control system design improvements, a robotic catheter
      system can accurately track the fast motion of the human mitral valve.

PMID- 29375927
TI  - Nickel/Photoredox-Catalyzed Amidation via Alkylsilicates and Isocyanates.
AB  - A nickel/photoredox, dual-catalyzed amidation reaction between alkylsilicate
      reagents and alkyl/aryl isocyanates is reported. In contrast to the previously
      reported reductive coupling process, this protocol is characterized by mild
      reaction conditions and the absence of a stoichiometric reductant. A mechanistic
      hypothesis involving a nickel-isocyanate adduct is proposed based on literature
      precedent and further validation by experimental results.

PMID- 29375929
TI  - Joint Learning of Representations of Medical Concepts and Words from EHR Data.
AB  - There has been an increasing interest in learning low-dimensional vector
      representations of medical concepts from electronic health records (EHRs). While
      EHRs contain structured data such as diagnostic codes and laboratory tests, they
      also contain unstructured clinical notes, which provide more nuanced details on a
      patient's health status. In this work, we propose a method that jointly learns
      medical concept and word representations. In particular, we focus on capturing
      the relationship between medical codes and words by using a novel learning scheme
      for word2vec model. Our method exploits relationships between different parts of
      EHRs in the same visit and embeds both codes and words in the same continuous
      vector space. In the end, we are able to derive clusters which reflect distinct
      disease and treatment patterns. In our experiments, we qualitatively show how our
      methods of grouping words for given diagnostic codes compares with a topic
      modeling approach. We also test how well our representations can be used to
      predict disease patterns of the next visit. The results show that our approach
      outperforms several common methods.

PMID- 29375928
TI  - Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward
      Medium-Chain-Length Fatty Acids.
AB  - Enzyme and metabolic engineering offer the potential to develop biocatalysts for
      converting natural resources into a wide range of chemicals. To broaden the scope
      of potential products beyond natural metabolites, methods of engineering enzymes
      to accept alternative substrates and/or perform novel chemistries must be
      developed. DNA synthesis can create large libraries of enzyme-coding sequences,
      but most biochemistries lack a simple assay to screen for promising enzyme
      variants. Our solution to this challenge is structure-guided mutagenesis in which
      optimization algorithms select the best sequences from libraries based on
      specified criteria (i.e. binding selectivity). Here, we demonstrate this approach
      by identifying medium-chain (C6-C12) acyl-ACP thioesterases through structure
      guided mutagenesis. Medium-chain fatty acids, products of thioesterase-catalyzed
      hydrolysis, are limited in natural abundance compared to long-chain fatty acids;
      the limited supply leads to high costs of C6-C10 oleochemicals such as fatty
      alcohols, amines, and esters. Here, we applied computational tools to tune
      substrate binding to the highly-active 'TesA thioesterase in Escherichia coli. We
      used the IPRO algorithm to design thioesterase variants with enhanced C12- or C8
      specificity while maintaining high activity. After four rounds of structure
      guided mutagenesis, we identified three thioesterases with enhanced production of
      dodecanoic acid (C12) and twenty-seven thioesterases with enhanced production of
      octanoic acid (C8). The top variants reached up to 49% C12 and 50% C8 while
      exceeding native levels of total free fatty acids. A comparably sized library
      created by random mutagenesis failed to identify promising mutants. The chain
      length-preference of 'TesA and the best mutant were confirmed in vitro using acyl
      CoA substrates. Molecular dynamics simulations, confirmed by resolved crystal
      structures, of 'TesA variants suggest that hydrophobic forces govern 'TesA
      substrate specificity. We expect that the design rules we uncovered and the
      thioesterase variants identified will be useful to metabolic engineering projects
      aimed at sustainable production of medium-chain oleochemicals.

PMID- 29375930
TI  - Auditing the Assignments of Top-Level Semantic Types in the UMLS Semantic Network
      to UMLS Concepts.
AB  - The Unified Medical Language System (UMLS) is an important terminological system.
      By the policy of its curators, each concept of the UMLS should be assigned the
      most specific Semantic Types (STs) in the UMLS Semantic Network (SN). Hence, the
      Semantic Types of most UMLS concepts are assigned at or near the bottom (leaves)
      of the UMLS Semantic Network. While most ST assignments are correct, some errors
      do occur. Therefore, Quality Assurance efforts of UMLS curators for ST
      assignments should concentrate on automatically detected sets of UMLS concepts
      with higher error rates than random sets. In this paper, we investigate the
      assignments of top-level semantic types in the UMLS semantic network to concepts,
      identify potential erroneous assignments, define four categories of errors, and
      thus provide assistance to curators of the UMLS to avoid these assignments
      errors. Human experts analyzed samples of concepts assigned 10 of the top-level
      semantic types and categorized the erroneous ST assignments into these four
      logical categories. Two thirds of the concepts assigned these 10 top-level
      semantic types are erroneous. Our results demonstrate that reviewing top-level
      semantic type assignments to concepts provides an effective way for UMLS quality
      assurance, comparing to reviewing a random selection of semantic type
      assignments.

PMID- 29375931
TI  - In-situ magnetization/heating electron holography to study the magnetic ordering
      in arrays of nickel metallic nanowires.
AB  - Magnetic nanostructures of different size, shape, and composition possess a great
      potential to improve current technologies like data storage and electromagnetic
      sensing. In thin ferromagnetic nanowires, their magnetization behavior is
      dominated by the competition between magnetocrystalline anisotropy (related to
      the crystalline structure) and shape anisotropy. In this way electron diffraction
      methods like precession electron diffraction (PED) can be used to link the
      magnetic behavior observed by Electron Holography (EH) with its crystallinity.
      Using off-axis electron holography under Lorentz conditions, we can
      experimentally determine the magnetization distribution over neighboring
      nanostructures and their diamagnetic matrix. In the case of a single row of
      nickel nanowires within the alumina template, the thin TEM samples showed a
      dominant antiferromagnetic arrangement demonstrating long-range magnetostatic
      interactions playing a major role.

PMID- 29375932
TI  - Characteristics of Cigarette Smoking in Individuals in Smoking Concordant and
      Smoking Discordant Couples.
AB  - Introduction: Partner smoking status may impact smoking cessation outcomes. The
      purpose of this study is to compare smokers in smoking concordant couples (both
      partners smoke) to smokers in smoking discordant couples (one partner smokes) on
      variables that have been shown to be important for quitting smoking. Methods:
      Participants were 123 cigarette smokers with cohabitating romantic partners
      (smoking discordant: n=60, smoking concordant: n=63, 63.9% females). We used one
      way MANCOVA, controlling for age and number of cigarettes smoked/day, to examine
      differences between groups on smoking outcome expectancies, motivation to quit
      smoking, and dyadic efficacy to quit smoking. We examined smoking behavior in a
      series of exploratory analyses. Results: We found a significant multivariate
      difference between individuals in smoking concordant and discordant couples (p <
      .05) such that 20.3% of the variation in the linear combination of dependent
      variables was accounted for by group membership. Follow-up univariate ANCOVA
      analyses indicated that those in smoking discordant couples reported greater
      positive outcome expectancies for cigarettes with regard to facilitating social
      situations and reducing boredom than those in the smoking concordant group.
      Participants in smoking concordant couples smoked more cigarettes when their
      partners were present, fewer cigarettes without their partners present, and were
      more likely to prefer that their partner be involved in their smoking cessation
      treatment than those in smoking discordant couples. Discussion: The results of
      this study may guide the development of smoking cessation interventions that
      attend to the unique needs of smoking concordant and discordant couples.

PMID- 29375933
TI  - Impact of Sleep Duration and Weekend Oversleep on Body Weight and Blood Pressure
      in Adolescents.
AB  - Introduction: Weekend oversleep or catchup sleep is a frequent occurrence in
      children, but there are relatively little data concerning its impact on weight
      and blood pressure. The aim of this study was to assess the association between
      sleep duration and oversleep, and weight and blood pressure in adolescents.
      Methods: Sleep duration, weight and blood pressure of 327 children (51.4% boys,
      mean age 13.3 +/- 1.7 years) who had polysomnograms performed during both exam
      cycles of the Tucson Children's Assessment of Sleep Apnea study (TuCASA) were
      analyzed. Sleep duration on school nights and non-school nights was used to
      compute a weighted average of child and parent reported overall sleep duration
      respectively. Oversleep was defined as the difference between self and parent
      reported weekend sleep and weekday sleep separately. Simple correlations between
      overall sleep duration, sleep on school and non-school nights and oversleep, and
      blood pressure, standardized body mass index (BMI), snoring, respiratory
      disturbance index (RDI) and age were calculated. Significant bivariate
      associations then were used to develop multivariate partial correlation models.
      Results: Unadjusted negative correlations with BMI were noted for parent reported
      total sleep duration at the 1st exam cycle, parent and child reported total sleep
      and school night sleep duration, and parent reported non-school night sleep
      duration at the 2nd exam cycle. Additionally, for BMI, positive correlations were
      observed for log RDI at both exam cycles and snoring at the 2nd exam cycle. For
      blood pressure, there were positive associations with age, parent reported
      oversleep, caffeine consumption and snoring. Additionally, for blood pressure,
      negative relationships were observed with parent reported total sleep duration at
      the 1st exam cycle, and parent and child reported total sleep and school night
      sleep durations at the 2nd exam cycle. Partial correlations found that BMI was
      negatively correlated with parent reported total sleep duration at the 1st exam
      cycle and parent reported total sleep duration at the 2nd exam cycle, and
      positively correlated with snoring and log RDI at both exam cycles. Systolic
      blood pressure was only associated with age and snoring. Diastolic blood pressure
      was positively correlated with age and caffeine consumption, and negatively
      correlated with parent reported total and school night sleep duration. Oversleep
      and child reported sleep duration were not represented in any of these models.
      Conclusion: Lower amounts of sleep especially on school nights is associated with
      higher body weight and blood pressure. Oversleep was not associated with either
      body weight or blood pressure.

PMID- 29375934
TI  - Rheumatoid Arthritis in Sickle-Cell Population: Pathophysiologic Insights,
      Clinical Evaluation and Management.
AB  - The advent of hydroxyurea and advanced medical care, including immunizations has
      led to improved survival among patients with Sickle Cell Disease (SCD). This
      prolonged survival however, introduces a chronic inflammatory disorder,
      Rheumatoid Arthritis (RA), which presents at a relatively older age and is rarely
      reported among SCD patients. In this review, we highlight the epidemiological
      association of SCD-RA and discuss the underlying common pathogenetic mechanisms,
      such as endothelial dysfunction, the role of inflammatory cytokines and oxidative
      stress. We also point to the difficulties in ascertaining the clinical diagnosis
      of RA in SCD patients. Finally, we provide rationale for therapeutic options
      available for RA and the challenges in the management of these patients with
      agents that are known to increase the risk of infection and immunosuppression
      such as steroids, disease modifying anti-rheumatic drugs and biologics.

PMID- 29375935
TI  - Antibody structure and engineering considerations for the design and function of
      Antibody Drug Conjugates (ADCs).
AB  - Antibody-drug conjugates (ADCs) are emerging as effective tools in cancer
      therapy, combining the antibody's exquisite specificity for the target antigen
      expressing cancer cell together with the cytotoxic potency of the payload. Much
      success stems from the rational design of "toxic warheads", chemically linked to
      antibodies, and from fine-tuning the intricate properties of chemical linkers.
      Here, we focus on the antibody moiety of ADCs, dissecting the impact of Fab,
      linkers, isotype and Fc structure on the anti-tumoral and immune-activating
      functions of ADCs. Novel design approaches informed by antibody structural
      attributes present opportunities that may contribute to the success of next
      generation ADCs.

PMID- 29375936
TI  - Antifibrotic effect of xanthohumol in combination with praziquantel is associated
      with altered redox status and reduced iron accumulation during liver fluke
      associated cholangiocarcinogenesis.
AB  - Cholangiocarcinoma (CCA) caused by infection of the liver fluke Opisthorchis
      viverrini, (Ov) is the major public health problem in northeast Thailand.
      Following Ov infection the subsequent molecular changes can be associated by
      reactive oxygen species (ROS) induced chronic inflammation, advanced periductal
      fibrosis, and cholangiocarcinogenesis. Notably, resistance to an activation of
      cell death in prolonged oxidative stress conditions can occur but some
      damaged/mutated cells could survive and enable clonal expansion. Our study used a
      natural product, xanthohumol (XN), which is an anti-oxidant and anti-inflammatory
      compound, to examine whether it could prevent Ov-associated CCA carcinogenesis.
      We measured the effect of XN with or without praziquantel (PZ), an anti
      helminthic treatment, on DNA damage, redox status change including iron
      accumulation and periductal fibrosis during CCA genesis induced by administration
      of Ov and N-dinitrosomethylamine (NDMA) in hamsters. Animals were randomly
      divided into four groups: group I, Ov infection and NDMA administration (ON);
      group II, Ov infection and NDMA administration and PZ treatment (ONP); the latter
      2 groups were similar to group I and II, but group III received additional XN
      (XON) and group IV received XN plus PZ (XONP). The results showed that high 8
      oxodG (a marker of DNA damage) was observed throughout cholangiocarcinogenesis.
      Moreover, increased expression of CD44v8-10 (a cell surface in regulation of the
      ROS defense system), whereas decreased expression of phospho-p38MAPK (a major ROS
      target), was found during the progression of the bile duct cell transformation.
      In addition, high accumulation of iron and expression of transferrin receptor-1
      (TfR-1) in both malignant bile ducts and inflammatory cells were detected.
      Furthermore, fibrosis also increased with the highest level being on day 180. On
      the other hand, the groups of XN with or without PZ supplementations showed an
      effective reduction in all the markers examined, including fibrosis when compared
      with the ON group. In particular, the XONP group, in which a significant
      reduction DNA damage occurred, was also found to have iron accumulation and
      fibrosis compared to the other groups. Our results show that XN administered in
      combination with PZ could efficiently prevent CCA development and hence provide
      potential chemopreventive benefits in Ov-induced cholangiocarcinogenesis.

PMID- 29375938
TI  - Identification of the fungal endophyte of Ammophila breviligulata (American
      beachgrass) as Epichloe amarillans.
AB  - The grass Ammophila breviligulata (American beachgrass) is known to host an
      endophyte of the genus Epichloe. Based on morphological characteristics it was
      originally identified as Acremonium typhinum var. ammophilae and is currently
      designated as Epichloe typhina var. ammophilae. However, the Epichloe species has
      not previously been identified based on DNA sequence data. Based on phylogenetic
      placement of beta-tubulin and translation elongation factor 1-alpha DNA sequences
      the endophyte is identified as a member of E. amarillans rather than E. typhina.

PMID- 29375937
TI  - Eukaryotes in the gut microbiota in myalgic encephalomyelitis/chronic fatigue
      syndrome.
AB  - Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often
      suffer from gastrointestinal symptoms and many are diagnosed with irritable bowel
      syndrome (IBS). Previous studies, including from our laboratory, have
      demonstrated that the ME/CFS gut bacterial composition is altered and less
      diverse when compared to healthy individuals. Patients have increased biomarkers
      of inflammation and leaky gut syndrome. To further investigate dysbiosis in the
      ME/CFS gut microbiome, we sought to characterize the eukaryotes present in the
      gut of 49 individuals with ME/CFS and 39 healthy controls. Using 18S rRNA
      sequencing, we have identified eukaryotes in stool samples of 17 healthy
      individuals and 17 ME/CFS patients. Our analysis demonstrates a small,
      nonsignificant decrease in eukaryotic diversity in ME/CFS patients compared to
      healthy individuals. In addition, ME/CFS patients show a nonsignificant increase
      in the ratio of fungal phyla Basidiomycota to Ascomycota, which is consistent
      with ongoing inflammation in ME/CFS. We did not identify specific eukaryotic taxa
      that are associated with ME/CFS disease status.

PMID- 29375939
TI  - Exotic Optical Fibers and Glasses: Innovative Material Processing Opportunities
      in Earth's Orbit.
AB  - Exotic optical fibers and glasses are the platform material for photonics
      applications, primarily due to their superior signal transmission (speed, low
      attenuation), with extending bandwidth deep into the infrared, exceeding that of
      silica fibers. Gravitational effects (convection sedimentation) have a direct
      impact on the phase diagram of these materials and influence melting properties,
      crystallization temperatures, and viscosity of the elemental mix during the
      manufacturing process. Such factors constitute limits to the yield, transmission
      quality, and strength and value of these fibers; they also constrain the range of
      applications. Manufacturing in a gravity-free environment such as the Earth's
      Orbit also helps with other aspects of the fabrication process (i.e., improved
      form factor of the manufacturing unit, sustainability). In this article,
      revolutionary developments in the field of photonics over the past decade merge
      with the paradigm shift in the privatization of government-owned capabilities
      supporting a more diverse infrastructure (parabolic, suborbital, orbital),
      reduced price, and increased frequency to access space and the microgravity
      environment. With the increased dependence on data (demand, bandwidth,
      efficiency), space and the microgravity environment provide opportunities for
      optimized performance of these exotic optical fibers and glasses underlying the
      development of enabling technologies to meet future data demand. Existing
      terrestrial markets (Internet, telecommunications, market transactions) and
      emerging space markets (on-orbit satellite servicing, space manufacturing, space
      resources, space communications, etc.) seem to converge, and this innovative
      material processing opportunity of exotic optical fibers and glasses might just
      be that "killer app": technologically competitive, economically viable, and with
      the ability to close the business case. 

PMID- 29375940
TI  - Visceroptosis and the Ehlers-Danlos Syndrome.
AB  - The case of a patient with visceroptosis and Ehlers-Danlos syndrome hypermobility
      type (RDS-HT) is reported here. The literature on this unusual but probably under
      recognized complication is reviewed.

PMID- 29375941
TI  - Use of Spinal Cord Stimulation in Elderly Patients with Multi-Factorial Chronic
      Lumbar and Non-Radicular Lower Extremity Pain.
AB  - Spinal cord stimulation (SCS) is an effective treatment for chronic back and limb
      pain. The criteria for use of SCS for specific problems such as failed back
      surgery syndrome (FBSS), peripheral neuropathic pain and residual pain after
      joint replacement is well established. With an aging population, there are more
      patients presenting with a combination of various multi-factorial chronic pain
      problems rather than from a single clear cause. It is not uncommon to see
      patients with chronic back pain years after spine surgery with new additional
      pain in the area of joint replacement or due to peripheral neuropathy. In most of
      these patients, one area is the primary cause of their pain, while the other more
      secondary. Multiple chronic problems complicate the pain management of the
      primary cause and also can diminish the effect of SCS that only targets the
      primary problem. The primary and secondary causes of pain were ranked by the
      patient including the duration of their chronic pain for each area. This helped
      establish criteria for use of SCS in these complex pain patients. The patients
      were evaluated initially with an epidural stimulator trial and if they obtained
      50% or greater pain relief to the primary pain generating area, permanent
      implantation of one or more arrays of spinal cord electrodes was performed but
      planned to cover also the secondary pain areas. Post-implant follow-up evaluation
      at one, three and six months included measurement of visual analog scale (VAS),
      use of pain medication and degree of functional activity and behavior. This
      report looks at the effectiveness of using multiple overlapping electrodes for
      SCS in patients with multi-factorial chronic pain.

PMID- 29375942
TI  - Pancreatic Divisum: An Unusual Cause of Chronic Pancreatitis in a Young Patient.
AB  - Pancreatic divisum is a condition that occurs in 4-14% of the population.
      Pancreatic divisum occurs in development when the ventral bud and dorsal bud of
      the pancreas fail to fuse. Patients with this condition are usually asymptomatic,
      however, 25-38% of these patients experience recurrent pancreatitis that may
      further progress to chronic pancreatitis. This case is of a 20-year-old female
      presenting with abdominal pain in the left and right upper quadrants of the
      abdomen with a significant history of recurrent pancreatitis since the age of
      seven. The patient was examined with computed tomography (CT), which identified
      pancreatitis. Further magnetic resonance cholangiopancreatography (MRCP) assisted
      in the diagnosis of a type III pancreatic divisum, given the remnant of short
      communication between the dorsal and ventral duct.

PMID- 29375943
TI  - Penetrating Obturator Artery Injury after Gunshot Wounds: A Successful
      Multidisciplinary Trauma Team Approach to a Potentially Lethal Injury.
AB  - Obturator artery injury (OAI) from pelvic gunshot wounds (GSW) is a rarely
      reported condition. Hemorrhages from pelvic trauma (PT) are mostly venous.
      Arterial hemorrhages represent about 10-20% of PTs. When arterial hemorrhages
      from PT occur, they are a severe and deadly complication often causing
      significant hemodynamic instability and eventual shock. A 23-year-old male
      presented to our emergency service via a private vehicle with multiple gunshot
      wounds to both thighs and to the lower back, resulted in rectal and obturator
      artery (OA) injuries. The patient underwent a successful coil-embolization of the
      right OA. Given the density of structures within the pelvis, patients who sustain
      gunshot wounds to the pelvic region are at high risk for injury to the small
      bowel, sigmoid colon, rectum, bladder, and/or vascular structures. While bleeding
      is the major cause of early mortality in PT, rectal injuries carry the highest
      mortality due to visceral injuries. A high clinical index of suspicion is needed
      to diagnose an iliac artery injury or injury to its branches. Prompt computed
      tomographic angiogram (CTA) and embolization of the OA is the best method to
      control and stop the bleeding and improve the mortality outcome. Clinicians
      caring for patients presenting with pelvic gunshot wounds should pay attention to
      the delayed presentation of internal hemorrhage from the OAs. A multidisciplinary
      team approach is crucial in the successful management of penetrating injuries to
      the obturator artery.

PMID- 29375944
TI  - A Dosimetric Comparison of Primary Chemoradiation Versus Postoperative Radiation
      for Locally Advanced Oropharyngeal Cancer.
AB  - Introduction Advanced-stage oropharyngeal cancer can be treated with primary
      chemoradiation (CRT) or primary surgery with adjuvant radiotherapy, both with
      similar survival outcomes. Though primary CRT prescribes a higher dose, adjuvant
      radiation requires irradiating the surgical bed, which may increase the high dose
      planned target volume (PTV). We hypothesize that the integral dose to the neck
      and dose to critical structures will be lower with primary CRT than adjuvant
      radiotherapy. Methods We selected the last 18 patients who underwent surgery and
      adjuvant radiotherapy at one institution between July 2015 and August 2016 with
      American Joint Committee on Cancer (AJCC) stage III or IVA oropharyngeal squamous
      cell cancer. Primary CRT treatment plans were created on the patients'
      preoperative computed tomography (CT) scans and prescribed 70 Gy in 33 fractions,
      while postoperative plans were prescribed 60 Gy in 30 fractions. The radiation
      doses received by organs at risk for each primary CRT plan were compared to the
      corresponding adjuvant radiation plan. Results  Primary CRT plans had
      significantly smaller high dose PTV than adjuvant radiation plans (187.3 cc (95%
      CI 134.9-239.7) and 466.3 cc (95% CI 356.7-575.9), p<0.0001). The neck integral
      dose was lower in 14 of 18 plans using primary CRT, although this was not
      statistically significant (p=0.5375). The primary CRT plans had lower mean doses
      to ipsilateral (31.8 Gy (95% CI 27.5-36.0) vs 39.3 Gy (95% CI 35.4-43.1),
      p=0.0009)) and contralateral parotid glands (22.5 Gy (95% CI 22.1-22.8) vs 27.6
      Gy (95% CI 23.4-31.8), p=0.0238) and larynx (20.7 Gy (95% CI 19.3-22.2) vs 40.2
      Gy (95% CI 30.8-46.6), p<0.0001). Conclusion Primary CRT offered a decreased neck
      integral dose, though it was statistically insignificant. Primary CRT plans
      reduce mean dose to larynx and parotid glands in comparison to postoperative
      radiation, which may result in lower toxicities. Clinical trials comparing
      primary CRT and primary surgery are warranted to compare patient toxicities.

PMID- 29375945
TI  - Superior Mesenteric Artery Syndrome: The Dark Side of Weight Loss.
AB  - Superior mesenteric artery (SMA) syndrome is a rare cause of small bowel
      obstruction (SBO) resulting from compression of the duodenum by the SMA. Patients
      at risk of developing SMA syndrome include those who have experienced rapid
      weight loss from chronic illnesses, malignancy, bariatric surgery, eating
      disorders, burns, trauma, or substance abuse. We present the case of a 54-year
      old cachectic female patient who presented with sudden onset nausea, vomiting,
      and severe epigastric pain. Imaging studies revealed distention of the stomach
      and proximal portion of the duodenum with abrupt narrowing of the third part of
      the duodenum consistent with SMA syndrome. A laparoscopy confirmed the diagnosis
      and duodenojejunostomy resulted in resolution of the symptoms.

PMID- 29375946
TI  - Malignant Mesothelioma of Tunica Vaginalis Testis: Macroscopic and Microscopic
      Features of a Very Rare Malignancy.
AB  - Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is an extremely
      rare tumour, usually mimicking benign pathologies of the scrotum. Our case is an
      84-year-old male patient who appealed with a painless, left-sided scrotal
      swelling longer than 2 months. Although the level of tumour markers was normal,
      ultrasonographic examination results forced us to perform an inguinal scrotal
      exploration. Multiple small papillary tumours, both on tunica vaginalis and
      tunica albuginea, were detected intraoperatively. Due to these findings, radical
      orchiectomy was performed. A pathological evaluation showed malignant
      mesothelioma (MM) of the tunica vaginalis testis. Exposure to asbestos is a well
      known risk factor. Furthermore, a history of trauma, herniorrhaphy and chronic
      hydroceles is blamed as a possible risk factor. Scrotal ultrasonography is the
      mainstay of primary diagnosis and, therefore, it should not be overlooked when
      dealing with benign scrotal cysts or hydroceles, which are very common
      pathologies at these decades, too. Radical inguinal orchiectomy is the primary
      treatment choice for localised MMTVT disease, whereas in signs of lymph node
      metastasis, inguinal lymph node dissection is required. Radical resection should
      be completed with chemotherapy and/or radiotherapy for an advanced or recurrent
      disease. This case, which is very rarely reported in the literature and detected
      during inguinal exploration, along with the pathological works that supported the
      diagnosis, was presented with this report.

PMID- 29375947
TI  - The Impact of Neurophysiological Intraoperative Monitoring during Spinal Cord and
      Spine Surgery: A Critical Analysis of 121 Cases.
AB  - Neuromonitoring has been utilized during spinal surgery to assess the function of
      the spinal cord in an effort to prevent intraoperative injury. Although its use
      is widespread, no clear benefit has been demonstrated. Our goal in this study was
      to interrogate the value of intraoperative neuromonitoring in decreasing the
      severity and rate of neurological injury during and after spinal surgery. Here we
      describe our experience of 121 patients who underwent spinal cord procedures with
      the combination of intraoperative neuromonitoring, to determine its ability to
      detect neurological changes and the specificity and sensitivity in this setting.
      The data for the 121 patients who underwent neurophysiological monitoring during
      various spinal procedures was collected retrospectively. The patients were
      classified into one of four groups according to the findings of intraoperative
      monitoring and the clinical outcomes on postoperative neurological exam.
      Intraoperative monitoring was evaluated for its specificity, sensitivity, and
      predictive value. In our cohort of 121 patients, the use of intraoperative
      neuromonitoring had a low sensitivity, which may produce an excessive number of
      false negatives. Based on these findings, neuromonitoring seems to have a poor
      positive predictive value and is thus an inappropriate test to prevent harm to
      patients.

PMID- 29375948
TI  - Vestibular Schwannoma Presenting with Bilateral Papilledema Without
      Hydrocephalus: Case Study.
AB  - Bilateral papilledema secondary to obstructive or communicating hydrocephalus in
      patients with vestibular schwannomas is a known presentation; however,
      papilledema in the absence of hydrocephalus is rarely reported and its mechanism
      is poorly understood. We report a case of a 20-year-old woman presenting with
      visual deterioration and bilateral papilledema on fundoscopy. Magnetic resonance
      imaging (MRI) revealed a giant vestibular schwannoma with no sign of
      hydrocephalus. The only imaging evidence of increased pressure on preoperative
      imaging studies was seen on a T2-weighted MRI, where there was subtle dilatation
      of the arachnoid space of the optic sleeve. We presume that this patient
      developed papilledema by some mechanism not connected to hydrocephalus. In a
      young patient, papilledema may be a sign preceding hydrocephalus, or she may have
      had pseudotumor cerebri concomitant with her vestibular schwannoma. In either
      case, removal of the vestibular schwannoma solved the problem. She had complete
      visual recovery, irrespective of the mechanism.

PMID- 29375949
TI  - Biliary Mucinous Cystic Neoplasm of the Liver with Ovarian Stroma and Elevated
      Serum and Cystic Fluid Cancer Antigen 19-9 Levels.
AB  - Biliary mucinous cystic neoplasms of the liver are rare cystic tumors comprising
      less than 5% of the liver cystic neoplasms. These tumors demonstrate a female
      predominance and entail a risk of malignant transformation. We present a 56-year
      old female patient with a multiloculated liver cystic lesion measuring 22 cm who
      underwent a cystectomy with en bloc resection of the liver segments II, III, and
      cholecystectomy. Serum cancer antigen 19.9 was 4,122.00 U/ml, supporting the
      diagnosis of a biliary cystic tumor. The cytology of the cystic fluid was
      negative for malignancy and intracystic fluid cancer antigen 19.9 level was
      measured over 12,000.00 U/l. The patient is free of recurrence at one-year follow
      up. Although a rare entity, the biliary mucinous cystic neoplasms should be
      considered in the differential diagnosis in the patients with liver cystic
      tumors. The appropriate management with complete surgical resection with negative
      margins is recommended given the risk of recurrence and malignant transformation.

PMID- 29375950
TI  - Embryonal Rhabdomyosarcoma of the Cervix: A Rare Disease at an Uncommon Age.
AB  - Embryonal rhabdomyosarcoma (RMS) is a rare type of sarcoma, primarily seen in the
      pediatric and adolescent population. Three subtypes of embryonal RMS are
      described, with the botryoid type being the most common. The incidence of this
      disease in adult females is 0.4% to 1% with the affected age group being patients
      in the third to fourth decade of life. It is exceedingly rare in patients above
      40 years of age. We describe the case of a 48-year-old female, gravida 9 para 5,
      who presented with abnormal vaginal bleeding and an exophytic mass on
      examination. Given her lack of requirement of maintaining parity, she underwent
      radical surgery. The tumor was 8 cm in the largest dimension with a high
      histologic grade and some cartilaginous differentiation. Immunohistochemical
      stains were positive for vimentin, CD99, myogenin, and MyoD1 consistent with a
      diagnosis of embryonal rhabdomyosarcoma, botryoid subtype. Based on high survival
      rates when treated with aggressive adjuvant chemotherapy, a decision was made to
      treat the patient with the ARST0331 regimen. We discuss the diagnostic pathologic
      features of the disease, the epidemiology, and the most common presentation along
      with prognostic factors, treatment strategies, and outcomes.

PMID- 29375951
TI  - Tale of a Wandering Lead: Late Atrial Lead Perforation into Right Lung following
      Pacemaker Implantation.
AB  - Cardiac perforation by a pacemaker lead is a rare complication of pacemaker
      implantation. Presentation can vary from chest pain and shortness of breath to
      the patient being completely asymptomatic. Diagnosis is usually made by high
      resolution computed tomography (HRCT) scan of the chest. Electrocardiograph (EKG)
      usually shows the absence of a paced rhythm, but it doesn't provide a definitive
      diagnosis. We describe a case of late cardiac perforation by an atrial pacemaker
      lead with no signs or symptoms of pericardial tamponade.

PMID- 29375952
TI  - Primary Cardiac High-grade Myxofibrosarcoma Presenting with Multiple Brain
      Metastases: A Case Report.
AB  - Herein we describe the case of a young patient who presented with a recent
      history of epilepsy due to multiple brain lesions; he did not complain about any
      cardiopulmonary impairments. The patient died as a consequence of hemorrhagic
      progression of brain metastatic disease. Regardless of a thorough investigation,
      the heart tumor remained occult. Primary cardiac tumors are very rare entities.
      Most of these are benign, but approximately 25% are malignant, and the majority
      of these are sarcomas. Myxofibrosarcoma and osteosarcoma are exceptionally rare.
      To date, we find only small series of cardiac myxofibrosarcoma, and to our
      knowledge, this one exceptionally presented with multiple brain metastatic
      lesions without cardiopulmonary symptoms.

PMID- 29375953
TI  - Candida Tropicalis Cholangitis in a Patient Without Underlying Malignancy.
AB  - Candida tropicalis is a rare cause of acute cholangitis, predominantly seen in
      patients with underlying hematological malignancies. Here, we describe a case of
      acute cholangitis caused by mixed organisms (Candida tropicalis, Candida
      albicans, and Enterococcus durans) without a known risk factor.

PMID- 29375954
TI  - An Unusual Presentation of Osteochondroma in a Sexagenarian.
AB  - Osteochondroma is the most commonly-found benign bone tumour. It is a benign,
      cartilaginous-capped bony projection. They are usually present on the bony
      surfaces of the long bones in adolescents and young adults. The risk of malignant
      transformation is <1% with solitary osteochondroma. We present a rare case of an
      osteochondroma in a patient with advanced age and an unusual location.

PMID- 29375955
TI  - Adsorption of aliphatic polyhydroxy carboxylic acids on gibbsite: pH dependency
      and importance of adsorbate structure.
AB  - Background: Aliphatic (poly)hydroxy carboxylic acids [(P)HCA] occur in natural,
      e.g. soils, and in technical (waste disposal sites, nuclear waste repositories)
      compartments . Their distribution, mobility and chemical reactivity, e.g. complex
      formation with metal ions and radionuclides, depend, among others, on their
      adsorption onto mineral surfaces. Aluminium hydroxides, e.g. gibbsite [alpha
      Al(OH)3], are common constituents of related solid materials and mimic the
      molecular surface properties of clay minerals. Thus, the study was pursued to
      characterize the adsorption of glycolic, threonic, tartaric, gluconic, and
      glucaric acids onto gibbsite over a wide pH and (P)HCA concentration range. To
      consider specific conditions occurring in radioactive wastes, adsorption applying
      an artificial cement pore water (pH 13.3) as solution phase was investigated
      additionally. Results: The sorption of gluconic acid at pH 4, 7, 9, and 12 was
      best described by the "two-site" Langmuir isotherm, combining "high affinity"
      sorption sites (adsorption affinity constants [Formula: see text] > 1 L mmol-1,
      adsorption capacities < 6.5 mmol kg-1) with "low affinity" sites ([Formula: see
      text] < 0.1 L mmol-1, adsorption capacities >= 19 mmol kg-1). The total
      adsorption capacities at pH 9 and 12 were roughly tenfold of that at pH 4 and 7.
      The S-shaped pH sorption edge of gluconic acid was modelled applying a constant
      capacitance model, considering electrostatic interactions, hydrogen bonding,
      surface complex formation, and formation of solved polynuclear complexes between
      Al3+ ions and gluconic acid. A Pearson and Spearman rank correlation between
      (P)HCA molecular properties and adsorption parameters revealed the high
      importance of the size and the charge of the adsorbates. Conclusions: The
      adsorption behaviour of (P)HCAs is best described by a combination of adsorption
      properties of carboxylic acids at acidic pH and of polyols at alkaline pH.
      Depending on the molecular properties of the adsorbates and on pH, electrostatic
      interactions, hydrogen bonding, and ternary surface complexation contribute in
      varying degrees to the adsorption process. Linear distribution coefficients Kd
      between 8.7 and 60.5 L kg-1 (1 mmol L-1 initial PHCA concentration) indicate a
      considerable mineral surface affinity at very high pH, thus lowering the PHCA
      fraction available for the complexation of metal ions including radionuclides in
      solution and their subsequent mobilization.

PMID- 29375956
TI  - Plasmonic- and dielectric-based structural coloring: from fundamentals to
      practical applications.
AB  - Structural coloring is production of color by surfaces that have microstructure
      fine enough to interfere with visible light; this phenomenon provides a novel
      paradigm for color printing. Plasmonic color is an emergent property of the
      interaction between light and metallic surfaces. This phenomenon can surpass the
      diffraction limit and achieve near unlimited lifetime. We categorize plasmonic
      color filters according to their designs (hole, rod, metal-insulator-metal,
      grating), and also describe structures supported by Mie resonance. We discuss the
      principles, and the merits and demerits of each color filter. We also discuss a
      new concept of color filters with tunability and reconfigurability, which enable
      printing of structural color to yield dynamic coloring at will. Approaches for
      dynamic coloring are classified as liquid crystal, chemical transition and
      mechanical deformation. At the end of review, we highlight a scale-up of
      fabrication methods, including nanoimprinting, self-assembly and laser-induced
      process that may enable real-world application of structural coloring.

PMID- 29375957
TI  - In-Gel Direct Laser Writing for 3D-Designed Hydrogel Composites That Undergo
      Complex Self-Shaping.
AB  - Self-shaping and actuating materials inspired by biological system have enormous
      potential for biosensor, microrobotics, and optics. However, the control of 3D
      complex microactuation is still challenging due to the difficulty in design of
      nonuniform internal stress of micro/nanostructures. Here, we develop in-gel
      direct laser writing (in-gel DLW) procedure offering a high resolution
      inscription whereby the two materials, resin and hydrogel, are interpenetrated on
      a scale smaller than the wavelength of the light. The 3D position and mechanical
      properties of the inscribed structures could be tailored to a resolution better
      than 100 nm over a wide density range. These provide an unparalleled means of
      inscribing a freely suspended microstructures of a second material like a
      skeleton into the hydrogel body and also to direct isotropic volume changes to
      bending and distortion motions. In the combination with a thermosensitive
      hydrogel rather small temperature variations could actuate large amplitude
      motions. This generates complex modes of motion through the rational engineering
      of the stresses present in the multicomponent material. More sophisticated
      folding design would realize a multiple, programmable actuation of soft
      materials. This method inspired by biological system may offer the possibility
      for functional soft materials capable of biomimetic actuation and photonic
      crystal application.

PMID- 29375959
TI  - Photodetectors Based on Organic-Inorganic Hybrid Lead Halide Perovskites.
AB  - Recent years have witnessed skyrocketing research achievements in organic
      inorganic hybrid lead halide perovskites (OIHPs) in the photovoltaic field. In
      addition to photovoltaics, more and more studies have focused on OIHPs-based
      photodetectors in the past two years, due to the remarkable optoelectronic
      properties of OIHPs. This article summarizes the latest progress in this research
      field. To begin with, the factors influencing the performance of photodetectors
      are discussed, including both internal and external factors. In particular, the
      channel width and the incident power intensities should be taken into account to
      precisely and objectively evaluate and compare the output performance of
      different photodetectors. Next, photodetectors fabricated on single-component
      perovskites in terms of different micromorphologies are discussed, namely, 3D
      thin-film and single crystalline, 2D nanoplates, 1D nanowires, and 0D
      nanocrystals, respectively. Then, bilayer structured perovskite-based
      photodetectors incorporating inorganic and organic semiconductors are discussed
      to improve the optoelectronic performance of their pristine counterparts.
      Additionally, flexible OIHPs-based photodetectors are highlighted. Finally, a
      brief conclusion and outlook is given on the progress and challenges in the field
      of perovskites-based photodetectors.

PMID- 29375958
TI  - Nanoparticle Superlattices: The Roles of Soft Ligands.
AB  - Nanoparticle superlattices are periodic arrays of nanoscale inorganic building
      blocks including metal nanoparticles, quantum dots and magnetic nanoparticles.
      Such assemblies can exhibit exciting new collective properties different from
      those of individual nanoparticle or corresponding bulk materials. However,
      fabrication of nanoparticle superlattices is nontrivial because nanoparticles are
      notoriously difficult to manipulate due to complex nanoscale forces among them.
      An effective way to manipulate these nanoscale forces is to use soft ligands,
      which can prevent nanoparticles from disordered aggregation, fine-tune the
      interparticle potential as well as program lattice structures and interparticle
      distances - the two key parameters governing superlattice properties. This
      article aims to review the up-to-date advances of superlattices from the
      viewpoint of soft ligands. We first describe the theories and design principles
      of soft-ligand-based approach and then thoroughly cover experimental techniques
      developed from soft ligands such as molecules, polymer and DNA. Finally, we
      discuss the remaining challenges and future perspectives in nanoparticle
      superlattices.

PMID- 29375960
TI  - Catalytic Effects in Lithium-Sulfur Batteries: Promoted Sulfur Transformation and
      Reduced Shuttle Effect.
AB  - Lithium-sulfur (Li-S) battery has emerged as one of the most promising next
      generation energy-storage systems. However, the shuttle effect greatly reduces
      the battery cycle life and sulfur utilization, which is great deterrent to its
      practical use. This paper reviews the tremendous efforts that are made to find a
      remedy for this problem, mostly through physical or chemical confinement of the
      lithium polysulfides (LiPSs). Intrinsically, this "confinement" has a relatively
      limited effect on improving the battery performance because in most cases, the
      LiPSs are "passively" blocked and cannot be reused. Thus, this strategy becomes
      less effective with a high sulfur loading and ultralong cycling. A more
      "positive" method that not only traps but also increases the subsequent
      conversion of LiPSs back to lithium sulfides is urgently needed to fundamentally
      solve the shuttle effect. Here, recent advances on catalytic effects in
      increasing the rate of conversion of soluble long-chain LiPSs to insoluble short
      chain Li2S2/Li2S, and vice versa, are reviewed, and the roles of noble metals,
      metal oxides, metal sulfides, metal nitrides, and some metal-free materials in
      this process are highlighted. Challenges and potential solutions for the design
      of catalytic cathodes and interlayers in Li-S battery are discussed in detail.

PMID- 29375962
TI  - Remarkable Enhancement of the Hole Mobility in Several Organic Small-Molecules,
      Polymers, and Small-Molecule:Polymer Blend Transistors by Simple Admixing of the
      Lewis Acid p-Dopant B(C6F5)3.
AB  - Improving the charge carrier mobility of solution-processable organic
      semiconductors is critical for the development of advanced organic thin-film
      transistors and their application in the emerging sector of printed electronics.
      Here, a simple method is reported for enhancing the hole mobility in a wide range
      of organic semiconductors, including small-molecules, polymers, and small
      molecule:polymer blends, with the latter systems exhibiting the highest mobility.
      The method is simple and relies on admixing of the molecular Lewis acid B(C6F5)3
      in the semiconductor formulation prior to solution deposition. Two prototypical
      semiconductors where B(C6F5)3 is shown to have a remarkable impact are the blends
      of 2,8-difluoro-5,11
      bis(triethylsilylethynyl)anthradithiophene:poly(triarylamine) (diF-TESADT:PTAA)
      and 2,7-dioctyl[1]-benzothieno[3,2-b][1]benzothiophene:poly(indacenodithiophene
      co-benzothiadiazole) (C8-BTBT:C16-IDTBT), for which hole mobilities of 8 and 11
      cm2 V-1 s-1, respectively, are obtained. Doping of the 6,13
      bis(triisopropylsilylethynyl)pentacene:PTAA blend with B(C6F5)3 is also shown to
      increase the maximum hole mobility to 3.7 cm2 V-1 s-1. Analysis of the single and
      multicomponent materials reveals that B(C6F5)3 plays a dual role, first acting as
      an efficient p-dopant, and secondly as a microstructure modifier. Semiconductors
      that undergo simultaneous p-doping and dopant-induced long-range crystallization
      are found to consistently outperform transistors based on the pristine materials.
      Our work underscores Lewis acid doping as a generic strategy towards high
      performance printed organic microelectronics.

PMID- 29375961
TI  - Progress and Perspective of Electrocatalytic CO2 Reduction for Renewable
      Carbonaceous Fuels and Chemicals.
AB  - The worldwide unrestrained emission of carbon dioxide (CO2) has caused serious
      environmental pollution and climate change issues. For the sustainable
      development of human civilization, it is very desirable to convert CO2 to
      renewable fuels through clean and economical chemical processes. Recently,
      electrocatalytic CO2 conversion is regarded as a prospective pathway for the
      recycling of carbon resource and the generation of sustainable fuels. In this
      review, recent research advances in electrocatalytic CO2 reduction are summarized
      from both experimental and theoretical aspects. The referred electrocatalysts are
      divided into different classes, including metal-organic complexes, metals, metal
      alloys, inorganic metal compounds and carbon-based metal-free nanomaterials.
      Moreover, the selective formation processes of different reductive products, such
      as formic acid/formate (HCOOH/HCOO-), monoxide carbon (CO), formaldehyde (HCHO),
      methane (CH4), ethylene (C2H4), methanol (CH3OH), ethanol (CH3CH2OH), etc. are
      introduced in detail, respectively. Owing to the limited energy efficiency,
      unmanageable selectivity, low stability, and indeterminate mechanisms of
      electrocatalytic CO2 reduction, there are still many tough challenges need to be
      addressed. In view of this, the current research trends to overcome these
      obstacles in CO2 electroreduction field are summarized. We expect that this
      review will provide new insights into the further technique development and
      practical applications of CO2 electroreduction.

PMID- 29375963
TI  - Zigzag-Elongated Fused pi-Electronic Core: A Molecular Design Strategy to
      Maximize Charge-Carrier Mobility.
AB  - Printed and flexible electronics requires solution-processable organic
      semiconductors with a carrier mobility (MU) of ~10 cm2 V-1 s-1 as well as high
      chemical and thermal durability. In this study, chryseno[2,1-b:8,7-b']dithiophene
      (ChDT) and its derivatives, which have a zigzag-elongated fused pi-electronic
      core (pi-core) and a peculiar highest occupied molecular orbital (HOMO)
      configuration, are reported as materials with conceptually new semiconducting pi
      cores. ChDT and its derivatives are prepared by a versatile synthetic procedure.
      A comprehensive investigation reveals that the ChDT pi-core exhibits increasing
      structural stability in the bulk crystal phase, and that it is unaffected by a
      variation of the transfer integral, induced by the perpetual molecular motion of
      organic materials owing to the combination of its molecular shape and its
      particular HOMO configuration. Notably, ChDT derivatives exhibit excellent
      chemical and thermal stability, high charge-carrier mobility under ambient
      conditions (MU <= 10 cm2 V-1 s-1), and a crystal phase that is highly stable,
      even at temperatures above 250  degrees C.

PMID- 29375964
TI  - Advanced Energy Storage Devices: Basic Principles, Analytical Methods, and
      Rational Materials Design.
AB  - Tremendous efforts have been dedicated into the development of high-performance
      energy storage devices with nanoscale design and hybrid approaches. The boundary
      between the electrochemical capacitors and batteries becomes less distinctive.
      The same material may display capacitive or battery-like behavior depending on
      the electrode design and the charge storage guest ions. Therefore, the underlying
      mechanisms and the electrochemical processes occurring upon charge storage may be
      confusing for researchers who are new to the field as well as some of the
      chemists and material scientists already in the field. This review provides
      fundamentals of the similarities and differences between electrochemical
      capacitors and batteries from kinetic and material point of view. Basic
      techniques and analysis methods to distinguish the capacitive and battery-like
      behavior are discussed. Furthermore, guidelines for material selection, the state
      of-the-art materials, and the electrode design rules to advanced electrode are
      proposed.

PMID- 29375965
TI  - Size-Controlled Graphene Nanodot Arrays/ZnO Hybrids for High-Performance UV
      Photodetectors.
AB  - Graphene nanodots (GNDs) are one of the most attractive graphene nanostructures
      due to their tunable optoelectronic properties. Fabricated by polystyrene
      nanosphere lithography, uniformly sized graphene nanodots array (GNDA) is
      constructed as an ultraviolet photodetector (PD) with ZnO nanofilm spin coated on
      it. The size of GNDA can be well controlled from 45 to 20 nm varying the etching
      time. It is revealed in the study that the photoelectric properties of ZnO/GNDA
      PD are highly GNDA size-dependent. The highest responsivity (R) and external
      quantum efficiency of ZnO/GNDA (20 nm) PD are 22.55 mA W-1 and 9.32%, almost
      twofold of that of ZnO PD. Both ZnO/GNDA (20 nm) PD and ZnO/GNDA (30 nm) PD
      exhibit much faster response speed under on/off switching light and have shorter
      rise/decay time compared with ZnO PD. However, as the size of GNDA increase to 45
      nm, the PD appears poor performance. The size-dependent phenomenon can be
      explained by the energy band alignments in ZnO/GNDA hybrids. These efforts reveal
      the enhancement of GNDs on traditional photodetectors with tunable optoelectronic
      properties and hold great potential to pave a new way to explore the various
      remarkable photodetection performances by controlling the size of the
      nanostructures.

PMID- 29375966
TI  - Earth-Abundant Tin Sulfide-Based Photocathodes for Solar Hydrogen Production.
AB  - Tin-based chalcogenide semiconductors, though attractive materials for
      photovoltaics, have to date exhibited poor performance and stability for
      photoelectrochemical applications. Here, a novel strategy is reported to improve
      performance and stability of tin monosulfide (SnS) nanoplatelet thin films for H2
      production in acidic media without any use of sacrificial reagent. P-type SnS
      nanoplatelet films are coated with the n-CdS buffer layer and the TiO2
      passivation layer to form type II heterojunction photocathodes. These
      photocathodes with subsequent deposition of Pt nanoparticles generate a
      photovoltage of 300 mV and a photocurrent density of 2.4 mA cm-2 at 0 V versus
      reversible hydrogen electrode (RHE) for water splitting under simulated visible
      light illumination (lambda > 500 nm, Pin = 80 mW cm-2). The incident photon-to
      current efficiency at 0 V versus RHE for H2 production reach a maximum of 12.7%
      at 575 nm with internal quantum efficiency of 13.8%. The faradaic efficiency for
      hydrogen evolution remains close to unity after 6000 s of illumination,
      confirming the robustness of the heterojunction for solar H2 production.

PMID- 29375967
TI  - Identifying the Cause of Rupture of Li-Ion Batteries during Thermal Runaway.
AB  - As the energy density of lithium-ion cells and batteries increases, controlling
      the outcomes of thermal runaway becomes more challenging. If the high rate of gas
      generation during thermal runaway is not adequately vented, commercial cell
      designs can rupture and explode, presenting serious safety concerns. Here, ultra
      high-speed synchrotron X-ray imaging is used at >20 000 frames per second to
      characterize the venting processes of six different 18650 cell designs undergoing
      thermal runaway. For the first time, the mechanisms that lead to the most
      catastrophic type of cell failure, rupture, and explosion are identified and
      elucidated in detail. The practical application of the technique is highlighted
      by evaluating a novel 18650 cell design with a second vent at the base, which is
      shown to avoid the critical stages that lead to rupture. The insights yielded in
      this study shed new light on battery failure and are expected to guide the
      development of safer commercial cell designs.

PMID- 29375968
TI  - Hydrothermal Cation Exchange Enabled Gradual Evolution of Au@ZnS-AgAuS Yolk-Shell
      Nanocrystals and Their Visible Light Photocatalytic Applications.
AB  - Yolk-shell hybrid nanoparticles with noble metal core and programmed
      semiconductor shell composition may exhibit synergistic effects and tunable
      catalytic properties. In this work, the hydrothermal cation exchange synthesis of
      Au@ZnS-AgAuS yolk-shell nanocrystals (Y-S NCs) with well-fabricated void size,
      grain-boundary-architectured ZnS-AgAuS shell and in situ generated Au cocatalyst
      are demonstrated. Starting from the novel cavity-free Au@AgAuS core-shell NCs,
      via aqueous cation exchange reaction with Zn2+, the gradual evolution with
      produced Au@ZnS-AgAuS Y-S NCs can be achieved successfully. This unprecedented
      evolution can be reasonably explained by cation exchange initialized chemical
      etching of Au core, followed by the diffusion through the shell to be AgAuS and
      then ZnS. By hydrothermal treatment provided optimal redox environment, Au ions
      in shell were partially reduced to be Au NCs on the surface. The UV-vis
      absorption spectra evolution and visible light photocatalytic performances,
      including improved photodegradation behavior and photocatalytic hydrogen
      evolution activity, have demonstrated their potential applications. This new one
      pot way to get diverse heterointerfaces for better photoinduced electron/hole
      separation synergistically can be anticipated for more kinds of photocatalytic
      organic synthesis.

PMID- 29375969
TI  - Development of Nanostructured Water Treatment Membranes Based on Thermotropic
      Liquid Crystals: Molecular Design of Sub-Nanoporous Materials.
AB  - Supply of safe fresh water is currently one of the most important global issues.
      Membranes technologies are essential to treat water efficiently with low costs
      and energy consumption. Here, the development of self-organized nanostructured
      water treatment membranes based on ionic liquid crystals composed of ammonium,
      imidazolium, and pyridinium moieties is reported. Membranes with preserved 1D or
      3D self-organized sub-nanopores are obtained by photopolymerization of ionic
      columnar or bicontinuous cubic liquid crystals. These membranes show salt
      rejection ability, ion selectivity, and excellent water permeability. The
      relationships between the structures and the transport properties of water
      molecules and ionic solutes in the sub-nanopores in the membranes are examined by
      molecular dynamics simulations. The results suggest that the volume of vacant
      space in the nanochannel greatly affects the water and ion permeability.

PMID- 29375970
TI  - Turning the Old Adjuvant from Gel to Nanoparticles to Amplify CD8+ T Cell
      Responses.
AB  - Due to its safety and efficacy, aluminum hydroxide is used as an immune adjuvant
      in human vaccines for over 80 years. Being a Th2 stimulator, the classical gel
      like adjuvant, however, fails to generate CD8+ T cell responses, which are
      important for cancer vaccines. Here, aluminum hydroxide is turned from gel into
      nano-sized vaccine carriers AlO(OH)-polymer nanoparticles (APNs) to promote their
      lymphatic migration. After actively uptaken via scavenger receptor-A by antigen
      presenting cells (APCs) resident in lymph nodes (LNs), APNs destabilize lysosomes
      resulting in efficient cytosolic delivery and cross-presentation of antigens. It
      is demonstrated that administration of APNs loaded with ovalbumin (OVA) and CpG
      led to the codelivery of both cargos into APCs in LNs, leading to their
      activation and subsequent adaptive immunity. A prime-boost strategy with low
      doses of OVA (1.5 ug) and CpG (0.45 ug) induces potent CD8+ T cell responses and
      dramatically prolongs the survival of B16-OVA tumor-bearing mice. More
      impressively, when using B16F10 lysates instead of OVA as antigen, substantial
      antitumor effects on B16F10 tumor model are observed by using APN-CpG. These
      results suggest the great potential of APNs as vaccine carriers that activate
      CD8+ T cell responses and the bright prospect of aluminum adjuvant in a
      nanoparticle formulation.

PMID- 29375971
TI  - Asymmetric Hybrid Polymer-Lipid Giant Vesicles as Cell Membrane Mimics.
AB  - Lipid membrane asymmetry plays an important role in cell function and activity,
      being for instance a relevant signal of its integrity. The development of
      artificial asymmetric membranes thus represents a key challenge. In this context,
      an emulsion-centrifugation method is developed to prepare giant vesicles with an
      asymmetric membrane composed of an inner monolayer of poly(butadiene)-b
      poly(ethylene oxide) (PBut-b-PEO) and outer monolayer of 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC). The formation of a complete membrane asymmetry
      is demonstrated and its stability with time is followed by measuring lipid
      transverse diffusion. From fluorescence spectroscopy measurements, the lipid half
      life is estimated to be 7.5 h. Using fluorescence recovery after photobleaching
      technique, the diffusion coefficient of 1,2-dioleoyl-sn-glycero-3
      phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (DOPE-rhod, inserted into
      the POPC leaflet) is determined to be about D = 1.8 +/- 0.50 MUm2 s-1 at 25 
      degrees C and D = 2.3 +/- 0.7 MUm2 s-1 at 37  degrees C, between the
      characteristic values of pure POPC and pure polymer giant vesicles and in good
      agreement with the diffusion of lipids in a variety of biological membranes.
      These results demonstrate the ability to prepare a cell-like model system that
      displays an asymmetric membrane with transverse and translational diffusion
      properties similar to that of biological cells.

PMID- 29375972
TI  - Nanomicelle-Assisted Targeted Ocular Delivery with Enhanced Antiinflammatory
      Efficacy In Vivo.
AB  - Ocular inflammations are common diseases that may lead to serious vision
      threatening obstacles. Eye drops for antiinflammation therapy need to be
      administered multiple times daily at a high dosage due to the rapid precorneal
      removal and low bioavailability of drugs. To overcome these problems, a cRGD
      functionalized DSPE-PEG2000 nanomicelle (DSPE-PEG2000-cRGD) encapsulated with
      flurbiprofen is proposed. The tailored nanomicelles trigger specific binding to
      integrin receptors on the ocular surface, which leads to rapid and robust
      mucoadhesion, superior ocular surface retention, and transcorneal penetration
      behaviors of nanomicelles. Due to the enhanced drug delivery on ocular surface
      and in aqueous humor, the functionalized nanoformulation significantly improves
      ocular antiinflammation efficacy at a low dosage by blocking the synthesis of
      inflammatory mediators and cytokines. The present study demonstrates a promising
      strategy that uses a functional peptide combined with nanomicelles for targeted
      delivery to the eye in ophthalmologic applications.

PMID- 29375973
TI  - Recent Progress in Single-Crystalline Perovskite Research Including Crystal
      Preparation, Property Evaluation, and Applications.
AB  - Organic-inorganic lead halide perovskites are promising optoelectronic materials
      resulting from their significant light absorption properties and unique long
      carrier dynamics, such as a long carrier lifetime, carrier diffusion length, and
      high carrier mobility. These advantageous properties have allowed for the
      utilization of lead halide perovskite materials in solar cells, LEDs,
      photodetectors, lasers, etc. To further explore their potential, intrinsic
      properties should be thoroughly investigated. Single crystals with few defects
      are the best candidates to disclose a variety of interesting and important
      properties of these materials, ultimately, showing the increased importance of
      single-crystalline perovskite research. In this review, recent progress on the
      crystallization, investigation, and primary device applications of single
      crystalline perovskites are summarized and analyzed. Further improvements in
      device design and preparation are also discussed.

PMID- 29375974
TI  - Aqueous-Containing Precursor Solutions for Efficient Perovskite Solar Cells.
AB  - Perovskite semiconductors have emerged as competitive candidates for photovoltaic
      applications due to their exceptional optoelectronic properties. However, the
      impact of moisture instability on perovskite films is still a key challenge for
      perovskite devices. While substantial effort is focused on preventing moisture
      interaction during the fabrication process, it is demonstrated that low moisture
      sensitivity, enhanced crystallization, and high performance can actually be
      achieved by exposure to high water content (up to 25 vol%) during fabrication
      with an aqueous-containing perovskite precursor. The perovskite solar cells
      fabricated by this aqueous method show good reproducibility of high efficiency
      with average power conversion efficiency (PCE) of 18.7% and champion PCE of 20.1%
      under solar simulation. This study shows that water-perovskite interactions do
      not necessarily negatively impact the perovskite film preparation process even at
      the highest efficiencies and that exposure to high contents of water can actually
      enable humidity tolerance during fabrication in air.

PMID- 29375975
TI  - Computational Intelligence-Assisted Understanding of Nature-Inspired
      Superhydrophobic Behavior.
AB  - In recent years, state-of-the-art computational modeling of physical and chemical
      systems has shown itself to be an invaluable resource in the prediction of the
      properties and behavior of functional materials. However, construction of a
      useful computational model for novel systems in both academic and industrial
      contexts often requires a great depth of physicochemical theory and/or a wealth
      of empirical data, and a shortage in the availability of either frustrates the
      modeling process. In this work, computational intelligence is instead used,
      including artificial neural networks and evolutionary computation, to enhance our
      understanding of nature-inspired superhydrophobic behavior. The relationships
      between experimental parameters (water droplet volume, weight percentage of
      nanoparticles used in the synthesis of the polymer composite, and distance
      separating the superhydrophobic surface and the pendant water droplet in adhesive
      force measurements) and multiple objectives (water droplet contact angle, sliding
      angle, and adhesive force) are built and weighted. The obtained optimal
      parameters are consistent with the experimental observations. This new approach
      to materials modeling has great potential to be applied more generally to aid
      design, fabrication, and optimization for myriad functional materials.

PMID- 29375976
TI  - Environment-Adaptive Coassembly/Self-Sorting and Stimulus-Responsiveness Transfer
      Based on Cholesterol Building Blocks.
AB  - Manipulating the property transfer in nanosystems is a challenging task since it
      requires switchable molecular packing such as separate aggregation (self-sorting)
      or synergistic aggregation (coassembly). Herein, a unique manipulation of self
      sorting/coassembly aggregation and the observation of switchable stimulus
      responsiveness transfer in a two component self-assembly system are reported. Two
      building blocks bearing the same cholesterol group give versatile topological
      structures in polar and nonpolar solvents. One building block (cholesterol
      conjugated cynanostilbene, CCS) consists of cholesterol conjugated with a
      cynanostilbene unit, and the other one (C10CN) is comprised of cholesterol
      connected with a naphthalimide group having a flexible long alkyl chain. Their
      assemblies including gel, crystalline plates, and vesicles are obtained. In gel
      and crystalline plate phases, the self-sorting behavior dominates, while
      synergistic coassembly occurs in vesicle phase. Since CCS having the
      cyanostilbene group can respond to the light irradiation, it undergoes light
      induced chiral amplification. C10CN is thermally responsive, whereby its
      supramolecular chirality is inversed upon heating. In coassembled vesicles, it is
      interestingly observed that their responsiveness can be transferred by each
      other, i.e., the C10CN segment is sensitive to the light irradiation, while CCS
      is thermoresponsive. This unprecedented behavior of the property transfer may
      shine a light to the precise fabrication of smart materials.

PMID- 29375977
TI  - Climate-Dependent Heat-Triggered Opening Mechanism of Banksia Seed Pods.
AB  - Heat-triggered fruit opening and delayed release of mature seeds are widespread
      among plants in fire-prone ecosystems. Here, the material characteristics of the
      seed-containing follicles of Banksia attenuata (Proteaceae), which open in
      response to heat frequently caused by fire, are investigated. Material analysis
      reveals that long-term dimensional stability and opening temperatures of
      follicles collected across an environmental gradient increase as habitats become
      drier, hotter, and more fire prone. A gradual increase in the biaxial curvature
      of the hygroscopic valves provides the follicles in the driest region with the
      highest flexural rigidity. The irreversible deformation of the valves for opening
      is enabled via a temperature-dependent reduction of the elastic modulus of the
      innermost tissue layer, which then allows releasing the stresses previously
      generated by shrinkage of the fiber bundles in the adjacent layer during follicle
      drying. These findings illustrate the level of sophistication by which this
      species optimizes its fruit opening mechanism over a large distribution range
      with varying environmental conditions, and may not only have great relevance for
      developing biomimetic actuators, but also for elucidating the species' capacity
      to cope with climatic changes.

PMID- 29375979
TI  - Imaging Inelastic Fracture Processes in Biomimetic Nanocomposites and Nacre by
      Laser Speckle for Better Toughness.
AB  - Mollusk nacre is a prototypical biological inorganic-organic composite that
      combines high toughness, stiffness, and strength by its brick-and-mortar
      microstructure, which has inspired several synthetic mimics. Its remarkable
      fracture toughness relies on inelastic deformations at the process zone at the
      crack tip that dissolve stress concentrations and stop cracks. The micrometer
      scale structure allows resolving the size and shape of the process zone to
      understand the fracture processes. However, for better scalability, nacre-mimetic
      nanocomposites with aligned inorganic or graphene nanosheets are extensively
      pursued, to avoid the packing problems of mesoscale sheets like in nacre or slow
      in situ biomineralization. This calls for novel methods to explore the process
      zone of biomimetic nanocomposites. Here the fracture of nacre and nacre-inspired
      clay/polymer nanocomposite is explored using laser speckle imaging that reveals
      the process zone even in absence of changes in optical scattering. To demonstrate
      the diagnostic value, compared to nacre, the nacre-inspired nanocomposite
      develops a process zone more abruptly with macroscopic crack deflection shown by
      a flattened process zone. In situ scanning electron microscopy suggests similar
      toughening mechanisms in nanocomposite and nacre. These new insights guide the
      design of nacre-inspired nanocomposites toward better mechanical properties to
      reach the level of synergy of their biological model.

PMID- 29375978
TI  - Electrochemically Synthesized Nanoporous Molybdenum Carbide as a Durable
      Electrocatalyst for Hydrogen Evolution Reaction.
AB  - Demands for sustainable production of hydrogen are rapidly increasing because of
      environmental considerations for fossil fuel consumption and development of fuel
      cell technologies. Thus, the development of high-performance and economical
      catalysts has been extensively investigated. In this study, a nanoporous Mo
      carbide electrode is prepared using a top-down electrochemical process and it is
      applied as an electrocatalyst for the hydrogen evolution reaction (HER). Anodic
      oxidation of Mo foil followed by heat treatment in a carbon monoxide (CO)
      atmosphere forms a nanostructured Mo carbide with excellent interconnections, and
      these structural characteristics lead to high activity and durability when
      applied to the HER. Additionally, characteristic behavior of Mo is observed;
      metallic Mo nanosheets form during electrochemical anodization by exfoliation
      along the (110) planes. These nanosheets are viable for chemical modification,
      indicating their feasibility in various applications. Moreover, the role of
      carbon shells is investigated on the surface of the electrocatalysts, whereby it
      is suggested that carbon shells serve as a mechanical barrier against the
      oxidative degradation of catalysts that accompanies unavoidable volume expansion.

PMID- 29375981
TI  - Starting the 5th Volume.

PMID- 29375980
TI  - High Thermoelectric Power Factor of High-Mobility 2D Electron Gas.
AB  - Thermoelectric conversion is an energy harvesting technology that directly
      converts waste heat from various sources into electricity by the Seebeck effect
      of thermoelectric materials with a large thermopower (S), high electrical
      conductivity (sigma), and low thermal conductivity (kappa). State-of-the-art
      nanostructuring techniques that significantly reduce kappa have realized high
      performance thermoelectric materials with a figure of merit (ZT =
      S2?sigma?T?kappa-1) between 1.5 and 2. Although the power factor (PF = S2?sigma)
      must also be enhanced to further improve ZT, the maximum PF remains near 1.5-4 mW
      m-1 K-2 due to the well-known trade-off relationship between S and sigma. At a
      maximized PF, sigma is much lower than the ideal value since impurity doping
      suppresses the carrier mobility. A metal-oxide-semiconductor high electron
      mobility transistor (MOS-HEMT) structure on an AlGaN/GaN heterostructure is
      prepared. Applying a gate electric field to the MOS-HEMT simultaneously modulates
      S and sigma of the high-mobility electron gas from -490 uV K-1 and ~10-1 S cm-1
      to -90 uV K-1 and ~104 S cm-1, while maintaining a high carrier mobility (~1500
      cm2 V-1 s-1). The maximized PF of the high-mobility electron gas is ~9 mW m-1 K
      2, which is a two- to sixfold increase compared to state-of-the-art practical
      thermoelectric materials.

PMID- 29375982
TI  - Experimental circumferential canaloplasty with a new Schlemm canal microcatheter.
AB  - AIM: To present a new, simple, inexpensive Schlemm canal microcatheter for
      circumferential canaloplasty in a rabbit model. METHODS: A rabbit glaucoma animal
      model was established by intravitreal injection of triamcinolone acetonide.
      Circumferential canaloplasty with a new Schlemm canal microcatheter (patent
      license number: 201220029850.0) was performed. The Schlemm canal microcatheter
      was composed of microcatheter wall and lumen. The wall was made of high
      refractive index plastic optical fiber that could be attached to an illuminant so
      that the whole lighted microcatheter was visible during circumferential
      canaloplasty. The lumen could be attached to an injector for injection of
      viscoelastic during catheterization. Rabbits were divided randomly into the
      control, model and treatment groups. Intraocular pressure (IOP) was measured with
      a Tono-pen tonometer pre-operation and 3, 7, 14, 21 and 28d post-operation.
      Ultrasound biomicroscopy was performed to visualize the Schlemm canal
      microcatheter in the Schlemm canal and the sclera pool. RESULTS: The Schlemm
      canal microcatheter could be used to perform circumferential canaloplasty in the
      rabbit glaucoma animal model. IOP was lower in the treatment group than that in
      the model group 3, 7, 14 and 28d after operation. There were no significant
      differences in IOP between the control group and treatment group. The differences
      among the three groups were statistically significant (3d: F=41.985, P<0.001; 7d:
      F=65.696, P<0.001; 14d: F=114.599, P<0.001; 28d: F=55.006, P<0.001). CONCLUSION:
      Circumferential canaloplasty is safe and effective in control of experimental
      glaucoma model in rabbits.

PMID- 29375983
TI  - Preloaded and non-preloaded intraocular lens delivery system and characteristics:
      human and porcine eyes trial.
AB  - AIM: To compare characteristics of preloaded and non-preloaded intraocular lens
      (IOL) delivery systems during IOL delivery procedures. METHODS: Total 101 human
      eyes were included in this prospective observational case series. Delivery
      characteristics of 5 types of IOLs including iSert250 NC60 (NC60), EnVista MX60
      (MX60), AcrySof IQ SN60WF (SN60WF), TECNIS ZCB00 (ZCB00), and TECNIS PCB00
      (PCB00) were investigated. NC60 and PCB00 were injected via preloaded delivery
      systems and other IOLs were injected via non-preloaded systems. In the human
      trial, time taken from IOL loading to completion of implantation was measured in
      all eyes undergoing conventional cataract surgery. Using 4 excised porcine eyes,
      dynamics of ophthalmic viscosurgical device (OVD) between an IOL injector and a
      porcine eye was analyzed using fluorescein sodium-stained OVD. RESULTS: The
      average time for IOL implantation was 22.0s for NC60, 43.2s for MX60, 32.3s for
      SN60WF, 41.4s for ZCB00, and 14.6s for PCB00 respectively. The number of cases
      with IOL manipulation with a second instrument was 6 for MX60, 2 for ZCB00, 0 for
      SN60WF, NC60, and PCB00. Amount of OVD pushed into a porcine eye was smaller with
      a preloaded system than with non-preloaded systems. CONCLUSION: IOL delivery with
      preloaded systems is faster and more predictable. Moreover, a preloaded delivery
      system shows relatively less OVD pushed into a porcine eye than non-preloaded
      systems.

PMID- 29375984
TI  - Hydrogen peroxide-induced apoptosis of human lens epithelial cells is inhibited
      by parthenolide.
AB  - AIM: To explore the effect of parthenolide on hydrogen peroxide (H2O2)-induced
      apoptosis in human lens epithelial (HLE) cells. METHODS: The morphology and
      number of apoptotic HLE cells were assessed using light microscopy and flow
      cytometry. Cell viability was tested by MTS assay. In addition, the expression of
      related proteins was measured by Western blot assay. RESULTS: Apoptosis of HLE
      cells was induced by 200 umol/L H2O2, and the viability of these cells was
      similar to the half maximal inhibitory concentration (IC50), as examined by MTS
      assay. In addition, cells were treated with either different concentrations
      (6.25, 12.5, 25 and 50 umol/L) of parthenolide along with 200 umol/L H2O2 or only
      50 umol/L parthenolide or 200 umol/L H2O2 for 24h. Following treatment with
      higher concentrations of parthenolide (50 umol/L), fewer HLE cells underwent H2O2
      induced apoptosis, and cell viability was increased. Further, Western blot assay
      showed that the parthenolide treatment reduced the expression of caspase-3 and
      caspase-9, which are considered core apoptotic proteins, and decreased the levels
      of phosphorylated nuclear factor-kappaB (NF-kappaB), ERK1/2 [a member of the
      mitogen-activated protein kinase (MAPK) family], and Akt proteins in HLE cells.
      CONCLUSION: Parthenolide may suppress H2O2-induced apoptosis in HLE cells by
      interfering with NF-kappaB, MAPKs, and Akt signaling.

PMID- 29375985
TI  - EDIL3 depletion suppress epithelial-mesenchymal transition of lens epithelial
      cells via transforming growth factor beta pathway.
AB  - AIM: To study the effect of discoidin I-like domaincontaining protein 3 (EDIL3)
      depletion on the proliferation and epithelial-mesenchymal transition (EMT) in
      human lens epithelial cells (LECs). METHODS: RNA interference was used to inhibit
      the expression of EDIL3 in human LECs in vitro. The morphology of cells was
      observed using an inverted microscope. Cell proliferation was assessed using EdU
      kit. Cell migration was investigated using Transwell chamber and EMT of LECs was
      assessed using confocal microscope and Western blotting. The transforming growth
      factor beta (TGFbeta) pathway was investigated using Western blotting. RESULTS:
      The data showed that silencing EDIL3 expression changed LECs morphology and
      suppressed LECs proliferation (P<0.05) and migration (P<0.01). Furthermore, the
      result of Western blotting showed that EDIL3 depletion reduced the expression of
      alpha-smooth muscle actin (alpha-SMA) (P<0.001) and vimentin (P<0.01), while
      increased the expression of E-cadherin (P<0.001). EDIL3 depletion could suppress
      the phosphorylation of Smad2 (P<0.01) and Smad3 (P<0.01) and the activation of
      exracellular signal regulated kinase (ERK) (P<0.05). CONCLUSION: The findings
      indicate that EDIL3 might participate in the proliferation and EMT in LECs via
      TGFbeta pathway and may be a potential therapeutic target for the treatment of
      posterior capsule opacification.

PMID- 29375986
TI  - Safety threshold of intravitreal clonidine in rabbit's eyes.
AB  - AIM: To determine the safe dose of intravitreal clonidine (IVC), a potential drug
      for neuroprotection and angiogenesis inhibition in rabbits. METHODS: A total of
      28 rabbits were divided into four groups. Three groups received IVC with
      concentrations of 15 (Group A), 25 (Group B), and 50 (Group C) ug/0.1 mL and the
      control group (Group D) received 0.1 mL balanced salt solution (BSS). To
      investigate IVC safety, electroretinography (ERG) was performed at baseline, then
      at 1, 4 and 8wk after injection. After last ERG, all rabbits were euthanized,
      their eyes were enucleated and subjected to routine histopathological evaluation,
      immunohistochemistry for glial fibrillary acidic protein (GFAP) and terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. RESULTS: Based
      on ERG, histopathology, GFAP and TUNEL assay findings, 15 ug IVC was determined
      as the safe dose in rabbit eyes. While, the results of routine histopathology and
      TUNEL assay were unremarkable in all groups, toxic effects attributed to 25 and
      50 ug IVC were demonstrated by ERG and GFAP tests. CONCLUSION: Totally 15 ug
      clonidine is determined as the safe dose for intravitreal injection in rabbits.
      Contribution of IVC in neuroprotection and inhibition of angiogenesis deserve
      more studies.

PMID- 29375987
TI  - A novel mutation in PRPF31, causative of autosomal dominant retinitis pigmentosa,
      using the BGISEQ-500 sequencer.
AB  - AIM: To study the genes responsible for retinitis pigmentosa. METHODS: A total of
      15 Chinese families with retinitis pigmentosa, containing 94 sporadically
      afflicted cases, were recruited. The targeted sequences were captured using the
      Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to
      the manufacturer's instructions. Data were aligned to UCSC Genome Browser build
      hg19, using the Burroughs Wheeler Aligner MEM algorithm. Local realignment was
      performed with the Genome Analysis Toolkit (GATK v.3.3.0) IndelRealigner, and
      variants were called with the Genome Analysis Toolkit Haplotypecaller, without
      any use of imputation. Variants were filtered against a panel derived from 1000
      Genomes Project, 1000G_ASN, ESP6500, ExAC and dbSNP138. In all members of Family
      ONE and Family TWO with available DNA samples, the genetic variant was validated
      using Sanger sequencing. RESULTS: A novel, pathogenic variant of retinitis
      pigmentosa, c.357_358delAA (p.Ser119SerfsX5) was identified in PRPF31 in 2 of 15
      autosomal-dominant retinitis pigmentosa (ADRP) families, as well as in one,
      sporadic case. Sanger sequencing was performed upon probands, as well as upon
      other family members. This novel, pathogenic genotype co-segregated with
      retinitis pigmentosa phenotype in these two families. CONCLUSION: ADRP is a
      subtype of retinitis pigmentosa, defined by its genotype, which accounts for 20%
      40% of the retinitis pigmentosa patients. Our study thus expands the spectrum of
      PRPF31 mutations known to occur in ADRP, and provides further demonstration of
      the applicability of the BGISEQ500 sequencer for genomics research.

PMID- 29375988
TI  - IgG4 and IgE co-positive group found in idiopathic orbital inflammatory disease.
AB  - AIM: To reveal the cytokines involved in idiopathic orbital inflammatory disease
      (IOID) and the relationship between Th17 cells, IgE and IOID pathogenesis.
      METHODS: Whole blood samples were processed immediately after collection and
      serological IgG4, IgG, and IgE antibodies were tested using ELISA. IOID and
      orbital cavernous hemangioma (CH) tissue samples underwent Bio-Plex multiplex
      cytokine detection. Hematoxylin-Eosin (HE) staining of all paraffin samples
      suggested the histological features of IOIDs, and expressions of IgG4 and IL-17A
      in affected tissues were detected by immunohistochemistry. RESULTS: Among 40 IOID
      plasma samples, 52.5% (21/40) were positive for IgG4 and 25% (10/40) were
      positive for IgE. Overlapped IgG4 or IgE positive samples accounted for 22.5%
      (9/40). Therefore, IOID samples were separated into three groups. The IgE+/IgG4+
      group had a relevantly lower level of pro-inflammatory cytokine expression. IL-4
      (Th2 cell related), IL-10 and TGF-beta1 (Treg cell immunity related) were
      elevated in all three groups. Some of the Th17 cell related cytokines (i.e. IL
      17A/F, IL-25, IL-23, and IL-33) displayed higher expression levels in the IgE
      /IgG4- group compared to the other two groups. CONCLUSION: We discovered an IgG4
      IgE co-positive group as well as Th17 cell immune involvement in IgG4-IgE co
      negative subgtroup in IOID for the first time. The pathogenesis of IOID could
      differ from different subgroups according to the IgG4 and IgE detection.
      Therefore, we recommend that, Treatment stratagy should be made according to the
      clinical assessment of IgG4-IgE and Th17 profile detection.

PMID- 29375989
TI  - A comparative study of risk factors for corneal infection in diabetic and non
      diabetic patients.
AB  - AIM: To compare the clinical characteristics of infectious keratopathy in type 2
      diabetes mellitus (T2DM) and non-diabetes mellitus (NDM) and to investigate risk
      factors for infectious keratopathy in T2DM patients. METHODS: Totally 230
      patients with T2DM and 168 with NDM diagnosed as infectious keratopathy were
      hospitalized at Qingdao Eye Hospital from 2001 to 2015. Data including sex, age,
      occupation, season, smoking and alcohol consumption habits, duration between
      onset and treatments, duration of hospitalization were collected. Initially
      identified indicators were analyzed with a multivariate logistic regression.
      Glycosylated hemoglobin A1c (HbA1c) in patients with T2DM was analyzed. The
      infectious keratopathies in the two groups were categorized and compared.
      RESULTS: The diabetic group consisted of 146 (63.5%) males and 84 (36.5%)
      females. The NDM group consisted of 111 (66.1%) males and 57 (33.9%) females.
      There was no signigicantly difference in sex distribution between the two groups
      (P>0.05). There were significant differences in age, occupation of patients,
      season of the onset of diseases, duration between onset and treatment, and
      durations of hospitalization between the two groups (P<0.05). In most of the
      patients in the diabetic group, the duration between onset and treatment was
      <=3mo, and most was >=3mo in the NDM group. Multivariate logistic regression
      analysis revealed that age and season were related to the development of corneal
      infection in the T2DM group (OR=1.709, 1.706). In the T2DM group, HbA1c was
      9.09%+/-2.12%. There were statistically significant differences in the incidences
      of bacterial keratitis and herpes simplex keratitis in the two groups (P<0.05),
      but no significant statistical difference was found between fungal keratitis and
      amoebic keratitis (P>0.05). CONCLUSION: Advanced age and the summer and winter
      seasons are identified as risk factors for infectious keratopathy in T2DM
      patients, and T2DM patients are more prone to bacterial keratitis.

PMID- 29375990
TI  - 5-year follow-up of combined non-topography guided photorefractive keratectomy
      and corneal collagen cross linking for keratoconus.
AB  - AIM: To evaluate the visual outcomes of simultaneous non-topography guided
      photorefractive keratectomy (PRK) and corneal collagen cross-linking (CXL) in
      eyes with keratoconus 5y after the procedure. METHODS: Prospective,
      interventional, non-randomized, and non-controlled case series design was used.
      Sixty eyes of 30 patients (16 males and 14 females; age: 21-41y) with mild, non
      progressive (stages 1-2) keratoconus were enrolled. Refraction, uncorrected
      distance visual acuity (UDVA) and corrected distance visual acuity (CDVA), flat
      and steep keratometry readings, and adverse events were evaluated preoperatively
      and postoperatively. Data were collected preoperatively and postoperatively at
      3mo, 1, 2, 3, 4, and 5y follow-up visits after combined non-topography-guided PRK
      with CXL was performed. All patients had at least 5y of follow-up. RESULTS: All
      study parameters showed a statistically significant improvement at 5y over
      baseline values. The mean follow-up time was 68.20+/-4.71mo (range: 60-106mo).
      Patients showed a significant improvement in UDVA from 1.24+/-0.79 logMAR prior
      to combined non-TG-PRK+CXL to 0.06+/-0.15 logMAR postoperatively at the time of
      their last follow-up visit. CDVA significantly increased from 0.06+/-0.19 logMAR
      preoperatively to 0.03+/-0.12 logMAR postoperatively. A significant decrease in
      the mean spherical equivalent (SE) refraction was observed from -2.28+/-1.8 to 
      0.79+/-0.93 diopters (D) (P<0.05), and the manifest sphere decreased from -1.62+/
      1.23 to -0.27+/-0.21 D (P=0.001). The manifest cylinder significantly decreased
      from -1.73+/-0.86 to -0.29+/-0.34 D postoperatively (P=0.001). The mean steep
      keratometry was 45.13+/-1.32 vs 47.28+/-2.12 D preoperatively (P<0.05), and the
      preoperative mean steepest keratometry (Kmax) 48.6+/-3.1 was reduced
      significantly to 46.8+/-2.9 postoperatively (P<0.05). CONCLUSION: Combined non-TG
      PRK with 15min CXL is an effective and safe option for correcting mild refractive
      error and improving visual acuity in patients with mild stable keratoconus.

PMID- 29375991
TI  - Descemet stripping automated endothelial keratoplasty in phakic eyes: incision
      modification reducing cataract formation.
AB  - AIM: To evaluate the efficacy of a technical modification to reduce the incidence
      of traumatic cataract induced by Descemet stripping automated endothelial
      keratoplasty (DSAEK) performed in phakic eyes. METHODS: A retrospective cohort
      study. The records of all patients with a clear crystalline lens and endothelial
      failure that underwent modified DSAEK at our insitution were reviewed. In this
      modification, in order to avoid inadvertent touch of the insertion forceps
      against the exposed crystalline lens while passing across the anterior chamber,
      the incision sites were shifted from the standard 9 and 3 o'clock positions,
      superiorly to the 10 and 2 o'clock position respectively. Formation of typically
      traumatic, anterior subcapsular cataract in these patients was compared to that
      observed in a cohort including all the patients with a clear crystalline lens and
      endothelial failure that underwent conventional DSAEK at our institution.
      RESULTS: The study group included 49 eyes following modified DSAEK and the
      control group included 35 eyes following DSAEK with conventional incision sites.
      Anterior subcapsular cataract occurring 4mo or less postoperatively was
      identified in 2 of 49 (4%) eyes in the study group and 7 of 35 (20%) eyes in the
      control group. The rates of traumatic cataract were significantly higher in the
      control group in comparison to the study group (P=0.03, RR=4.9, 95%CI 1.08-22.1).
      CONCLUSION: Traumatic cataract formation following phakic DSAEK may be avoided
      with a simple modification to the position of the incision sites.

PMID- 29375992
TI  - Effect of infusion pressure during cataract surgery on ganglion cells measured
      using isolated-check visual evoked potential.
AB  - AIM: To detect the relationship between infusion pressure and postoperative
      ganglion cells function. METHODS: This prospective observational cohort study
      included sixty-one eyes that underwent uncomplicated cataract surgery. Patients
      were divided into two groups according to infusion time (IT) recorded using
      surgery equipment [Group A: IT>ITmean (27 eyes); Group B: IT<ITmean (34 eyes)].
      Best-corrected visual acuity, isolated-check visual evoked potential (icVEP),
      microperimetry, and optical coherence tomography examinations were performed
      preoperatively and 1wk and 1mo postoperatively. The changes in test results were
      measured with independent-sample t-tests and paired t-tests. Correlation between
      IT and these changes were analyzed with Pearson's correlation analysis and
      Spearman correlation analysis. RESULTS: Neither group showed significant
      postoperative changes in macular ganglion cell-inner plexiform layer (mGC-IPL)
      thickness (1-week postoperative: Group A P=0.185, Group B P=0.381; 1-month
      postoperative: Group A P=0.775, Group B P=0.652). Postoperative mGC-IPL thickness
      of Group A was not significantly thicker than that of Group B at both post
      surgery time point (1-week postoperative P=0.913; 1-month postoperative P=0.954).
      In Group A, the mGC-IPL thickness change 1wk postoperatively was positively
      correlated with IT (R2=0.156, P=0.0198). A suspected progressive deficit in the
      magnocellular pathway was also found in Group A 1-month postoperatively
      [individual observed F (IOF)=0.63+/-0.70]. Significant increases were observed in
      postoperative retinal sensitivity measured by microperimetry (1-week
      postoperative: Group A P=0.015, Group B P<0.001; 1-month postoperative: Group A
      P=0.005, Group B P<0.001). In Group B, IT was negatively correlated with the
      increase in macular sensitivity (1-week postoperative: R2=0.372, P<0.001; 1-month
      postoperative: R2=0.209, P=0.007). CONCLUSION: Both mGC-IPL thickness and retinal
      sensitivity increased postoperatively. A suspected progressive deficit in the
      magnocellular pathway was found in the group with a long IT, which induced more
      prominent changes.

PMID- 29375993
TI  - Comparison of long-term results of trabeculectomy to treat pseudoexfoliative
      glaucoma and primary open angle glaucoma.
AB  - AIM: To compare the long term outcome of trabeculectomy in patients with
      pseudoexfoliative glaucoma (PEG) and primary open angle glaucoma (POAG) in terms
      of surgical success. METHODS: The success of the trabeculectomy was evaluated by
      three criteria. Criterion A: intraocular pressure (IOP) <=21 mm Hg and decrease
      in IOP >=20%; Criterion B: IOP <=18 mm Hg and decrease in IOP >=30%; Criterion C:
      IOP <=15 mm Hg and decrease in IOP >=50%. Patients that met these criteria
      without medical treatment were considered to be completely successful, while
      those that met these criteria with medical treatment were considered partially
      successful. Significance levels of differences between the POAG and PEG groups in
      the Kaplan-Meier survival curves were calculated with the log-rank test. RESULTS:
      Sixty-four eyes from 64 patients with PEG and 51 eyes from 51 patients with POAG
      were evaluated. No significant differences were detected between the PEG and POAG
      groups according to full or partial success relative to each of the three
      criteria (A: P=0.73, 0.32; B: P=0.73, 0.31; C:P=0.90, 0.27). CONCLUSION: There is
      no difference in the long-term success of trabeculectomy between PEG and POAG
      patients whose clinical characteristics are otherwise the same.

PMID- 29375994
TI  - Efficacy of selective laser trabeculoplasty following incisional glaucoma
      surgery.
AB  - AIM: To evaluate the efficacy of selective laser trabeculoplasty (SLT) in
      glaucomatous eyes with previous incisional glaucoma surgery. METHODS: A
      retrospective cohort of eyes that underwent SLT at a single institution from 2013
      2015 were followed for 1y. Reduction in intraocular pressure (IOP) following SLT
      was evaluated in eyes with prior trabeculectomy with ExPress mini shunt (Alcon,
      Ft Worth, TX, USA), Ahmed valve (New World Medical, Cucamonga, CA, USA), or
      combined phacoemulsification-trabeculectomy. A control group was included with
      eyes without prior surgery that underwent SLT. Success was defined as >20% drop
      in IOP from pre-SLT baseline. RESULTS: One-hundred and six eyes were included
      with 53 in both the prior glaucoma surgery (PGS) and no prior glaucoma surgery
      (NPGS) groups. Mean pre-SLT IOP was 19.2+/-4.3 and 20.6+/-6.0 mm Hg for PGS and
      NPGS groups, respectively (P=0.17). Both groups produced statistically
      significant IOP reductions at 1 and 6mo (P<0.04). At 6mo, mean IOP reduction
      reached 7.3% and 10.8% for the PGS and NPGS groups, respectively (P=0.42).
      Overall, 27.9% and 31.7% of eyes in PGS and NPGS groups met success criteria at
      1y (P=0.70). In the PGS group, eyes with baseline IOP >=21 mm Hg had IOP
      reductions of 18.1% (P<0.001), 16.7% (P<0.01), and 8.4% (P=0.31) compared to eyes
      with baseline IOP <21 mm Hg who had IOP reductions of 2.3% (P=0.39), 3.4%
      (P=0.19), and 1.1% (P=0.72) at 1, 6mo, and 1y, respectively. CONCLUSION: SLT is
      efficacious in eyes with prior incisional glaucoma surgery and results in similar
      IOP reductions compared to eyes without PGS. A larger IOP reduction is observed
      following SLT in eyes with higher pre-SLT IOP.

PMID- 29375995
TI  - Intravitreal dexamethasone implants for diabetic macular edema.
AB  - AIM: To evaluate the safety and efficacy of a dexamethasone (DEX) intravitreal
      implant for diabetic macular edema (DME). METHODS: Totally 113 eyes of 84
      patients were divided in three subgroups: naive patients (n=11), pseudophakic
      patients (n=72) and phakic patients (n=30). Inclusive criterion comprised adult
      diabetic patients with central fovea thickening and impaired visual acuity
      resulting from DME for whom previous standard treatments showed no improvement in
      both central macular thickness (CMT) and best corrected visual acuity (BCVA)
      after at least 3mo of treatment. Outcome data were obtained from patient visits
      at baseline and at months 1, 3, 5, 9 and 12 after the first DEX implant
      injection. At each of these visits, patients underwent measurement of BCVA, a
      complete eye examination and measurement of CMT and macular volume (MV) carried
      out with optical coherence tomography (OCT) images. RESULTS: Seventy-three eyes
      (64.5%) received a single implant, 30 (26.5%) received two implants and 10 (9%)
      received three implants. At baseline, average in BCVA, CMT and MV were 43.5+/
      20.8, 462.8+/-145 and 12.6+/-2.5 respectively. These values improved
      significantly at 1mo (BCVA: 47.2+/-19.5, CMT: 339.6+/-120, MV: 11.11+/-1.4) and
      3mo (BCVA: 53.2+/-18.1, CMT: 353.8+/-141, MV: 11.3+/-1.3) (P<=0.05). At 5mo
      (BCVA: 50.9+/-19.8, CMT: 425+/-150, MV: 12.27+/-2.3), 9mo (BCVA: 48.4+/-17.6,
      CMT: 445.5+/-170, MV: 12.5+/-2.3) and 12mo (BCVA: 47.7+/-18.8, CMT: 413.2+/-149,
      MV: 12.03+/-2.5), improvements in the three parameters were no longer
      statistically significant and decreased progressively but did not reach baseline
      values. There were no clinical differences between subgroups. Ocular
      complications were minimal. CONCLUSION: Patients with DEX implants show maximum
      efficacy at 3mo which then declined progressively, but is still better than
      baseline values at the end of follow-up.

PMID- 29375996
TI  - Final anatomic and visual outcomes appear independent of duration of silicone oil
      intraocular tamponade in complex retinal detachment surgery.
AB  - AIM: To report anatomic and visual outcomes following silicone oil removal in a
      cohort of patients with complex retinal detachment, to determine association
      between duration of tamponade and outcomes and to compare patients with oil
      removed and those with oil in situ in terms of demographic, surgical and visual
      factors. METHODS: We reported a four years retrospective case series of 143
      patients with complex retinal detachments who underwent intraocular silicone oil
      tamponade. Analysis between anatomic and visual outcomes, baseline demographics,
      duration of tamponade and number of surgical procedures were carried out using
      Fisher's exact test and unpaired two-tailed t-test. RESULTS: One hundred and six
      patients (76.2%) had undergone silicone oil removal at the time of review with 96
      patients (90.6%) showing retinal reattachment following oil removal. Duration of
      tamponade was not associated with final reattachment rate or with a deterioration
      in best corrected visual acuity (BCVA). Patients with oil removed had a
      significantly better baseline and final BCVA compared to those under oil
      tamponade (P=0.0001, <0.0001 respectively). CONCLUSION: Anatomic and visual
      outcomes in this cohort are in keeping with those reported in the literature.
      Favorable outcomes were seen with oil removal but duration of oil tamponade does
      not affect final attachment rate with modern surgical techniques and should be
      managed on a case by case basis.

PMID- 29375997
TI  - Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis
      optica.
AB  - AIM: To determine the thickness of the retinal ganglion cell-inner plexiform
      layer (GCIPL) and the retinal nerve fiber layer (RNFL) in patients with
      neuromyelitis optica (NMO). METHODS: We conducted a cross-sectional study that
      included 30 NMO patients with a total of 60 eyes. Based on the presence or
      absence of optic neuritis (ON), subjects were divided into either the NMO-ON
      group (30 eyes) or the NMO-ON contra group (10 eyes). A detailed ophthalmologic
      examination was performed for each group; subsequently, the GCIPL and the RNFL
      were measured using high-definition optical coherence tomography (OCT). RESULTS:
      In the NMO-ON group, the mean GCIPL thickness was 69.28+/-21.12 um, the minimum
      GCIPL thickness was 66.02+/-10.02 um, and the RNFL thickness were 109.33+/-11.23,
      110.47+/-3.10, 64.92+/-12.71 and 71.21+/-50.22 um in the superior, inferior,
      temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean
      GCIPL thickness was 85.12+/-17.09 um, the minimum GCIPL thickness was 25.39+/
      25.1 um, and the RNFL thicknesses were 148.33+/-23.22, 126.36+/-23.45, 82.21+/
      22.30 and 83.36+/-31.28 um in the superior, inferior, temporal and nasal
      quadrants, respectively. In the control group, the mean GCIPL thickness was
      86.98+/-22.37 um, the minimum GCIPL thickness was 85.28+/-10.75 um, and the RNFL
      thicknesses were 150.22+/-22.73, 154.79+/-60.23, 82.33+/-7.01 and 85.62+/-13.81
      um in the superior, inferior, temporal and nasal quadrants, respectively. The
      GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group
      (P<0.05); additionally, the RNFL was thinner in the inferior quadrant in the NMO
      ON group than in the control group (P<0.05). Significant correlations were
      observed between the GCIPL and RNFL thickness measurements as well as between
      thickness measurements and the two visual field parameters of mean deviation (MD)
      and corrected pattern standard deviation (PSD) in the NMO-ON group (P<0.05).
      CONCLUSION: The thickness of the GCIPL and RNFL, as measured using OCT, may
      indicate optic nerve damage in patients with NMO.

PMID- 29375998
TI  - Effect of body position on the pathogenesis of asymmetric primary open angle
      glaucoma.
AB  - AIM: To explore the pathogenesis of asymmetric primary open angle glaucoma (POAG)
      in both eyes by comparing the intraocular pressure (IOP) of patients who sleep in
      different positions and to investigate the relationship between IOP variations
      and sleep positions. METHODS: One hundred and thirty-one patients with asymmetric
      POAG and forty-six healthy volunteers were enrolled. All participants completed a
      questionnaire that provided information about their sleep laterality. The cup
      disc ratio (C/D) and visual field defect established binocular asymmetry. The IOP
      of both eyes was measured using iCare parameters after the patients were asked to
      change body position. The "worse" and "better" eyes were identified according to
      the diagnosis, whereas the "dependent" and "independent" eyes were defined
      according to the lateral position. RESULTS: No significant difference in sleep
      laterality was observed between healthy people and patients with POAG (F=3.195,
      P=0.362). Among the enrolled patients, the IOP of the dependent eye was always
      greater than that of the independent eye in the lateral position (P<0.05). In the
      patients with binocular asymmetric POAG, the questionnaire clearly showed that
      85.7% of left side preferences were found their left eyes to be the worse eyes
      and the right eyes of 71.4% patients with a right side preference were the more
      serious. When the asymmetric C/D ratio was greater than or equal to 0.2, the
      worse eye of patients with POAG and a preferred sleeping position was the
      dependent eye (chi2 =16.762, P=0.001). CONCLUSION: A higher IOP was measured in
      the dependent eye in the lateral position. The long-term tendency to choose a
      lateral sleeping position might lead the dependent eye to manifest more severe
      symptoms than the independent eye. Thus, the lateral sleeping position might be
      one cause of asymmetric POAG.

PMID- 29375999
TI  - Roles of the eye care workforce for task sharing in management of diabetic
      retinopathy in Cambodia.
AB  - AIM: To identify the current roles of eye and health care workers in eye care
      delivery and investigate their potential roles in screening and detection for
      management of diabetic retinopathy (DR) through task sharing. METHODS: Purposive
      sampling of 24 participants including health administrators, members from non
      government organizations and all available eye care workers in Takeo province
      were recruited. This cross sectional mixed method study comprised a survey and in
      depth interviews. Data were collected from medical records at Caritas Takeo Eye
      Hospital (CTEH) and Kiri Vong District Referral Hospital Vision Centre, and a
      survey and interviews with participants were done to explore the potential roles
      for task sharing in DR management. Qualitative data were transcribed into a text
      program and then entered into N-Vivo (version 10) software for data management
      and analysis. RESULTS: From 2009 to 2012, a total of 105 178 patients were
      examined and 14 030 eye surgeries were performed in CTEH by three
      ophthalmologists supported by ophthalmic nurses in operating and eye examination
      for patients. Between January 2011 and September 2012, 151 patients (72 males)
      with retinal pathology including 125 (83%) with DR visited CTEH. In addition 170
      patients with diabetes were referred to CTEH for eye examinations from Mo Po Tsyo
      screening programs for people with diabetes. Factors favouring task sharing
      included high demand for eye care services and scarcity of ophthalmologists.
      CONCLUSION: Task sharing and team work for eye care services is functional.
      Participants favor the potential role of ophthalmic nurses in screening for DR
      through task sharing.

PMID- 29376000
TI  - The Beijing Desheng Diabetic Eye Study: rationale, design, methodology and
      baseline data.
AB  - AIM: To present the rationale, design, methodology, and the baseline data of the
      Beijing Desheng Diabetic Eye Study (BDDES), and to determine the prevalence of
      diabetic retinopathy (DR) and possible risk factors in patients with type 2
      diabetes mellitus (T2DM) in an urban community of Beijing, China. METHODS:
      Community-based prospective cohort study of persons diagnosed with T2DM aged 30y
      or older. The main variables of interest are the presence and progression of DR
      as determined by the standardized ETDRS grading of seven fields fundus
      photographs. The presence and severity of DR were analyzed for possible
      correlations to non-genetic and genetic dispositions. RESULTS: A total of 1438
      participants with data available for analysis, the prevalence of any DR was
      35.4%. The prevalence of mild non-proliferative diabetic retinopathy (NPDR),
      moderate NPDR, severe NPDR, and proliferative diabetic retinopathy was 27.7%,
      2.6%, 0.5% and 4.5%, respectively. By multiple logistic regression analysis, risk
      factors for the presence of any DR included male (P=0.031), lower income level
      (P=0.011), lower education background (P=0.022), longer duration of diabetes
      (P=0.001), younger age at diabetic onset (P=0.001), higher systolic blood
      pressure (P=0.007), higher glycosylated hemoglobin A1c levels (P=0.001), high
      albuminuria (P=0.03), and use of insulin (P<0.001). For vision-threatening DR,
      four factors were significant: younger age at diabetic onset (P<0.001), higher
      systolic blood pressure (P=0.042), high albuminuria (P<0.001), and use of insulin
      (P<0.001). CONCLUSION: The BDDES is the first large-scale ongoing cohort study of
      a Chinese urban population of persons with type 2 diabetes. Using standardized
      grading system comparable to large cohort studies from western populations, our
      baseline data shows that the prevalence of DR and major risk factors in this
      Chinese ethnic population are comparable to that found in the western population
      studies.

PMID- 29376001
TI  - Genes and genetics in eye diseases: a genomic medicine approach for investigating
      hereditary and inflammatory ocular disorders.
AB  - Past 25y have witnessed an exponential increase in knowledge and understanding of
      ocular diseases and their respective genetic underpinnings. As a result,
      scientists have mapped many genes and their variants that can influence vision
      and health of our eyes. Based on these findings, it is becoming clear that an
      early diagnosis employing genetic testing can help evaluate patients' conditions
      for instituting treatment plan(s) and follow-up care to avoid vision
      complications later. For example, knowing family history becomes crucial for
      inherited eye diseases as it can benefit members in family who may have similar
      eye diseases or predispositions. Therefore, gathering information from an
      elaborate examination along with complete assessment of past medical illness by
      ophthalmologists followed by consultation with geneticists can help create a
      roadmap for making diagnosis and treatment precise and beneficial. In this
      review, we present an update on ocular genomic medicine that we believe has
      tremendous potential towards unraveling genetic implications in ocular diseases
      and patients' susceptibilities. We also discuss translational aspects of genetic
      ophthalmology and genome engineering that may help advance molecular diagnostics
      and therapeutics.

PMID- 29376002
TI  - A feasibility study of using biodegradable magnesium alloy in glaucoma drainage
      device.
AB  - Technological advances in glaucoma have challenged the traditional treatment
      paradigm. Historically incisional surgery has been used in cases of advanced
      disease and/or uncontrolled intraocular pressures resistant to medical or laser
      interventions. More recently, perhaps due to advancements in imaging, surgery has
      been suggested to be beneficial earlier in the treatment paradigm. Despite these
      trends, surgical manipulation of the tissues and unpredictability of wound
      healing continue to result in surgical failure. Magnesium is an essential element
      for human body and plays a critically important role in maintaining the
      functional and structural integrity of several tissues, including the eye. Due to
      several of its advantageous properties such as non-toxicity, biodegradability,
      and high biological compatibility, magnesium alloy has attracted great attention
      as a novel biomaterial. Biodegradable cardiovascular stents made of magnesium
      alloy have already been introduced into clinical practice. The purpose of this
      review is to determine if bioabsorbable magnesium alloys can be utilized as a
      promising candidate for the development of a new generation of glaucoma surgical
      assistive devices.

PMID- 29376005
TI  - Amniotic membrane transplantation with topical interferon alfa-2b after excision
      of ocular surface squamous neoplasia.
AB  - To evaluate the outcome of amniotic membrane transplantation (AMT) after tumor
      excision followed by topical interferon alfa-2b (IFNalpha2b) drops for primary
      ocular surface squamous neoplasia (OSSN). Twelve eyes of 12 patients with a mean
      age of 66+/-10y were included. The average follow-up was 23+/-10mo. All 12
      patients had limbal involvement. Smooth ocular surface and transparent cornea
      were achieved in all cases. No sign of inflammation, neovascularization,
      symblepharon or recurrence was noted at the last follow-up. We conclude that AMT
      with topical IFNalpha2b drops restores a healthy ocular surface in OSSN without
      recurrence.

PMID- 29376006
TI  - Prevalence of glaucoma in the Israeli Arab population.
AB  - We describe the prevalence and treatment of glaucoma in a Muslim Arab population
      in Israel. Based on the medical records of 15 122 persons, the overall prevalence
      of glaucoma was 3.9%. Prevalence rates of primary open angle glaucoma (POAG) and
      primary angle-closure glaucoma (PACG) were 3.0% and 0.42%, respectively.
      Prevalence rates of women were 135% that of men considering all types of
      glaucoma, 143% for POAG, and 96% for PACG. Prostaglandin analogs and beta
      blockers, alone or combined with carbonic anhydrase inhibitors, were the
      preferred medications. Of 68 patients who underwent trabeculectomy, 27 (39.7%)
      required medications, postoperatively, for treatment of glaucoma; following Ex
      Press shunt surgery, 3/11 (27.3%) required medications. During the last three
      years, 16 (1.3%) individuals with POAG were recorded as legally blind as a result
      of glaucoma.

PMID- 29376003
TI  - The role of microglia in the progression of glaucomatous neurodegeneration- a
      review.
AB  - Glaucoma is a serious leading cause of irreversible blindness worldwide. Reducing
      intraocular pressure (IOP) does not always stop glaucomatous neurodegeneration
      and the optic nerve may continue to be damaged in the normal IOP. Microglial
      activity has been recognized to play essential roles in pathogenesis of the
      central nervous system (CNS) as well as retinal ganglion cell (RGC) survival. The
      relationship between the neurodegeneration and the microglia cells in glaucoma is
      very complicated and still remains unclear. In the present review, we summarize
      the recent studies of mechanisms of microglia in glaucoma neurodegeneration,
      which might provide new ways to treat glaucoma.

PMID- 29376007
TI  - Effect of two different doses of intravitreal bevacizumab with temporal retina
      sparing laser photocoagulation for retinopathy of prematurity.
AB  - This study aims to compare the efficacy and safety between two different doses of
      intravitreal bevacizumab (IVB) injection with temporal retina-sparing laser
      (TRSL) photocoagulation for retinopathy of prematurity (ROP). We retrospectively
      evaluated 22 eyes of ROP infants who underwent IVB combined with partial TRSL for
      stage 3+ zone I or posterior zone II ROP. Laser photocoagulation was applied on
      the avascular retina, sparing two-disc-diameter width temporal avascular area
      anterior to ridge. A half dose (0.625 mg) or minimal dose (0.25 mg) of IVB was
      conducted. Four eyes in minimal dose group were retreated with IVB and laser
      photocoagulation on the spared retina. Of those 4 retreated eyes, three developed
      preretinal hemorrhage around the ridge after the first treatment, resulting in
      fibrotic macular dragging. A half dose of IVB may be more effective than a
      minimal dose with partial TRSL for ROP. Preretinal hemorrhage may be a harbinger
      of poor prognosis.

PMID- 29376004
TI  - Application of stem cell-derived retinal pigmented epithelium in retinal
      degenerative diseases: present and future.
AB  - As a constituent of blood-retinal barrier and retinal outer segment (ROS)
      scavenger, retinal pigmented epithelium (RPE) is fundamental to normal function
      of retina. Malfunctioning of RPE contributes to the onset and advance of retinal
      degenerative diseases. Up to date, RPE replacement therapy is the only possible
      method to completely reverse retinal degeneration. Transplantation of human RPE
      stem cell-derived RPE (hRPESC-RPE) has shown some good results in animal models.
      With promising results in terms of safety and visual improvement, human embryonic
      stem cell-derived RPE (hESC-RPE) can be expected in clinical settings in the near
      future. Despite twists and turns, induced pluripotent stem cell-derived RPE (iPSC
      RPE) is now being intensely investigated to overcome genetic and epigenetic
      instability. By far, only one patient has received iPSC-RPE transplant, which is
      a hallmark of iPSC technology development. During follow-up, no major
      complications such as immunogenicity or tumorigenesis have been observed. Future
      trials should keep focusing on the safety of stem cell-derived RPE (SC-RPE)
      especially in long period, and better understanding of the nature of stem cell
      and the molecular events in the process to generate SC-RPE is necessary to the
      prosperity of SC-RPE clinical application.

PMID- 29376008
TI  - Tissue plasminogen activator-assisted vitrectomy in the early treatment of acute
      massive suprachoroidal hemorrhage complicating cataract surgery.

PMID- 29376009
TI  - A new treatment option for the resistant spasm of accommodation: clear lens
      extraction and multifocal intraocular lens implantation.

PMID- 29376012
TI  - Fertility preservation during cancer treatment: The Korean Society for Fertility
      Preservation clinical guidelines.
AB  - While many fertility preservation (FP) options now exist for reproductive-aged
      cancer patients, access to these services continues to be limited. A
      comprehensive FP program should be organized to serve oncofertility patients
      effectively. Also, much effort is needed from various individuals-patients,
      specialists from various fields, and consultants-to facilitate FP in a timely
      manner. Various challenges still exist in improving access to FP programs. To
      improve access to FP treatment, it is important to educate oncologists and
      patients via electronic tools and to actively navigate patients through the
      system. Reproductive endocrinology practices that receive oncofertility referrals
      must be equipped to provide a full range of options on short notice. A
      multidisciplinary team approach is required, involving physicians, nurses, mental
      health professionals, office staff, and laboratory personnel. The bottom line of
      FP patient care is to understand the true nature of each patient's specific
      situation and to develop a patient flow system that will help build a successful
      FP program. Expanding the patient flow system to all comprehensive cancer centers
      will ensure that all patients are provided with adequate information regarding
      their fertility, regardless of geography.

PMID- 29376011
TI  - Developing a deeper insight into reproductive biomarkers.
AB  - The development of biomarkers of reproductive medicine is still in its infancy
      because many black boxes are still present in reproductive medicine. Novel
      approaches to human infertility diagnostics and treatment must be developed
      because reproductive medicine has lagged behind in the implementation of
      biomarkers in clinical medicine. Despite the dearth of the available literature,
      the current rapid pace of publications suggests that this gap will soon be filled
      therefore; this review is a precis of the research that has been done so far and
      will provide a basis for the development of biomarkers in reproductive medicine.

PMID- 29376013
TI  - Fertility preservation for patients with gynecologic malignancies: The Korean
      Society for Fertility Preservation clinical guidelines.
AB  - Fertility preservation plays a central role in cancer care since an increasingly
      large number of cancer patients are surviving as a result of improvements in
      diagnostic and therapeutic strategies. Physicians who take part in the initial
      diagnosis and management of gynecologic cancer should understand the importance
      of fertility preservation. Since indications for fertility preservation are
      limited to early-stage gynecologic cancer, a surgeon must carefully consider each
      indication. Before performing fertility-sparing surgery, health professionals
      should compare its oncologic and pregnancy outcomes with those of other standard
      treatments. Individualized treatment strategies should be delivered depending on
      the patient's situation, and physicians should provide timely information and
      appropriate counseling.

PMID- 29376014
TI  - Fertility preservation for patients with breast cancer: The Korean Society for
      Fertility Preservation clinical guidelines.
AB  - With advances in the methods of cancer treatment used in modern medicine, the
      number of breast cancer survivors has been consistently rising. As the number of
      women who wish to become pregnant after being diagnosed with breast cancer
      increases, it is necessary to consider fertility preservation in these patients.
      However, medical doctors may be unaware of the importance of fertility
      preservation among cancer patients because most patients do not share their
      concerns about fertility with their doctors. Considering the time spent choosing
      and undergoing treatment, an early referral to a reproductive specialist is the
      best way to prevent a delay in cancer treatment. Since it is not easy to make
      decisions on matters related to cancer diagnosis and fertility, patients should
      be provided with enough time for decision-making, and to allow for this, an early
      referral will provide patients with sufficient time to choose an appropriate
      method of fertility preservation. The currently available options of fertility
      preservation for patients with breast cancer include cryopreservation of embryos,
      oocytes, and ovarian tissue and gonadotropin-releasing hormone agonist treatment
      before and during chemotherapy. An appropriate method of fertility preservation
      must be selected through consultations between individual patients and health
      professionals and analyses of the pros and cons of different options.

PMID- 29376015
TI  - Fertility preservation for patients with hematologic malignancies: The Korean
      Society for Fertility Preservation clinical guidelines.
AB  - Although the survival rate of hematologic malignancies in young patients is very
      high, cytotoxic therapies such as chemotherapy and total body irradiation therapy
      can significantly reduce a patient's reproductive capacity and cause irreversible
      infertility. Early ovarian failure also commonly occurs following additional
      cancer treatment, bone marrow transplantation, or autologous transplantation.
      Because the risk of early ovarian failure depends on the patient's circumstances,
      patients with a hematologic malignancy must consult health professionals
      regarding fertility preservation before undergoing treatments that can
      potentially damage their ovaries. While it is widely known that early menopause
      commonly occurs following breast cancer treatment, there is a lack of reliable
      study results regarding fertility preservation during hematologic malignancy
      treatment. Therefore, an in-depth discussion between patients and health
      professionals about the pros and cons of the various options for fertility
      preservation is necessary. In this study, we review germ cell toxicity, which
      occurs during the treatment of hematologic malignancies, and propose guidelines
      for fertility preservation in younger patients with hematologic malignancies.

PMID- 29376016
TI  - Effects of laser-assisted hatching and exposure time to vitrification solution on
      mouse embryo development.
AB  - Objective: This study was conducted to investigate the efficacy of laser-assisted
      hatching (LAH) and various vitrification times for embryonic development and
      blastocyst cell numbers. Methods: First, 2-cell and 8-cell embryos were collected
      by flushing out the oviducts. In the control groups, they were vitrified for 8 or
      10 minutes without LAH. The LAH groups underwent quarter laser zona thinning
      assisted hatching before vitrification (4, 6, and 8 minutes or 4, 7, and 10
      minutes, respectively). After incubation, double-immunofluorescence staining was
      performed. Results: The hatched blastocyst rate 72 hours after the 2-cell embryos
      were thawed was significantly higher in the 2LAH-ES8 group (33.3%) than in the
      other groups (p<0.05). In the control-8 group (22.1+/-4.6), the cell number of
      the inner cell mass was higher than in the LAH groups (p<0.05). The number of
      trophectoderm cells was higher in the 2LAH-ES6 group (92.8+/-8.9) than in the
      others (p<0.05). The hatched blastocyst rate 48 hours after the 8-cell embryos
      were thawed was higher in the 8LAH-ES4 group (45.5%) than in the other groups,
      but not significantly. The inner cell mass cell number was highest in the 8LAH
      ES7 group (19.5+/-5.1, p<0.05). The number of trophectoderm cells was higher in
      the 8LAH-ES10 group (73.2+/-12.1) than in the other groups, but without
      statistical significance. Conclusion: When LAH was performed, 2-cell embryos with
      large blastomeres had a lower hatched blastocyst rate when the exposure to
      vitrification solution was shorter. Conversely, 8-cell embryos with small
      blastomere had a higher hatched blastocyst rate when the exposure to
      vitrification solution was shorter.

PMID- 29376017
TI  - Sperm DNA fragmentation and sex chromosome aneuploidy after swim-up versus
      density gradient centrifugation.
AB  - Objective: The aim of this study was to compare the efficacy of swim-up and
      density gradient centrifugation (DGC) for reducing the amount of sperm with
      fragmented DNA, sex chromosome aneuploidy, and abnormal chromatin structure.
      Methods: Semen samples were obtained from 18 healthy male partners who attended
      infertility clinics for infertility investigations and were processed with swim
      up and DGC. The percentages of sperm cells with fragmented DNA measured by the
      sperm chromatin dispersion test, normal sex chromosomes assessed by fluorescence
      in situ hybridization, and abnormal chromatin structure identified by toluidine
      blue staining were examined. Results: The percentage of sperm cells with
      fragmented DNA was significantly lower in the swim-up fraction (9.7%, p=0.001)
      than in the unprocessed fraction (27.0%), but not in the DGC fraction (27.8%,
      p=0.098). The percentage of sperm cells with normal X or Y chromosomes was
      comparable in the three fractions. The percentage of sperm cells with abnormal
      chromatin structure significantly decreased after DGC (from 15.7% to 10.3%,
      p=0.002). The swim-up method also tended to reduce the percentage of sperm cells
      with abnormal chromatin structure, but the difference was not significant (from
      15.7% to 11.6%, p=0.316). Conclusion: The swim-up method is superior for
      enriching genetically competent sperm.

PMID- 29376018
TI  - Effects of infections with five sexually transmitted pathogens on sperm quality.
AB  - Objective: This study investigated the prevalence of infections with human
      papillomavirus, Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma
      hominis, and Mycoplasma genitalium in the semen of Korean infertile couples and
      their associations with sperm quality. Methods: Semen specimens were collected
      from 400 men who underwent a fertility evaluation. Infection with above five
      pathogens was assessed in each specimen. Sperm quality was compared in the
      pathogen-infected group and the non-infected group. Results: The infection rates
      of human papillomavirus, C. trachomatis, U. urealyticum, M. hominis, and M.
      genitalium in the study subjects were 1.57%, 0.79%, 16.80%, 4.46%, and 1.31%,
      respectively. The rate of morphological normality in the U. urealyticum-infected
      group was significantly lower than in those not infected with U. urealyticum. In
      a subgroup analysis of normozoospermic samples, the semen volume and the total
      sperm count in the pathogen-infected group were significantly lower than in the
      non-infected group. Conclusion: Our results suggest that infection with U.
      urealyticum alone and any of the five sexually transmitted infections are likely
      to affect sperm morphology and semen volume, respectively.

PMID- 29376019
TI  - T helper cell subsets and related cytokines in infertile women undergoing in
      vitro fertilization before and after seminal plasma exposure.
AB  - Objective: In vitro fertilization (IVF) is a well-known method for the treatment
      of infertility. The present study aimed to compare the differences between
      infertile women with successful and unsuccessful IVF outcomes regarding the
      expression of T helper (Th) cell transcription factors and a group of related
      cytokines before and after exposure to their husbands' seminal plasma. Methods:
      This study was performed on 19 couples with unexplained infertility undergoing
      IVF treatment. Among the studied group, nine and 10 couples had successful and
      unsuccessful IVF outcomes, respectively. This study was carried out using real
      time polymerase chain reaction. Results: Before seminal plasma exposure, the
      expression levels of T-bet (p<0.007), interferon-gamma (p=0.013), and tumor
      necrosis factor (TNF)-alpha (p=0.017) were higher in the infertile women with IVF
      failure than in those with successful IVF outcomes, while those of GATA3
      (p<0.001), Foxp3 (p=0.001), and interleukin (IL)-35 (p<0.003) were lower. After
      seminal exposure, the expression of T-bet (p=0.02), Rorc (p<0.001), TNF-alpha
      (p=0.001), Foxp3 (p=0.02), and interferon-gamma (p=0.001) increased in the
      unsuccessful IVF group, while the expression of Foxp3 (p=0.02), Rorc (p<0.001),
      IL-23 (p=0.04), IL-17 (p=0.02), IL-6 (p<0.001), transforming growth factor-beta
      (p=0.01), and IL-35 (p<0.001) increased in the successful IVF group. Conclusion:
      In summary, IVF failure was associated with imbalanced Th1/Th2/Th17/Treg
      responses. Moreover, our results show that seminal plasma might have a positive
      effect on IVF outcomes via changes in peripheral blood T cell subsets.

PMID- 29376020
TI  - Impact of sperm DNA fragmentation on clinical in vitro fertilization outcomes.
AB  - Objective: We studied the association between sperm DNA fragmentation (SDF) and
      several clinical in vitro fertilization outcomes. Methods: We retrospectively
      analyzed 169 consecutive fresh IVF cycles. Semen was collected on the day of
      oocyte retrieval, and we assessed standard semen parameters and the SDF level (by
      terminal deoxynucleotidyl transferase dUTP nick-end labeling). Poor ovarian
      response (POR) was defined as the collection of three or fewer mature oocytes.
      Oocytes were inseminated by the conventional method or intracytoplasmic sperm
      injection. Results: SDF did not affect the fertilization or pregnancy rate, but
      did have a significant effect on the miscarriage rate. In the miscarriage group
      (n=10), the SDF level was significantly higher (23.9% vs. 14.1%) and number of
      mature oocytes was significantly lower (4.3 vs. 7.6) than in the live birth group
      (n=45). Multiple regression analysis showed that SDF was an independent predictor
      of miscarriage (odds ratio, 1.051; 95% confidence interval, 1.001-1.104). The
      cutoffs for the SDF level and number of mature oocytes that could predict
      miscarriage were >13% and <=3, respectively. In the low-SDF group (<=13%), the
      miscarriage rate was similar in POR patients and those with a normal ovarian
      response (NOR; 14.2% vs. 4.3%). In the high-SDF group (>13%), the miscarriage
      rate was significantly higher in the POR group than in the NOR group (60.0% vs.
      13.3%, p=0.045). Conclusion: Our study demonstrated that a high SDF level (>13%)
      was associated with a high miscarriage rate, and that it mainly contributed to
      miscarriage in the POR group. The results suggest that SDF measurements should be
      considered in couples with POR in order to predict the prognosis of the
      pregnancy.

PMID- 29376021
TI  - Reduction of the cetrorelix dose in a multiple-dose antagonist protocol and its
      impact on pregnancy rate and affordability: A randomized controlled multicenter
      study.
AB  - Objective: To determine whether reducing the cetrorelix dose in the antagonist
      protocol to 0.125 mg had any deleterious effects on follicular development, the
      number and quality of retrieved oocytes, or the number of embryos, and to
      characterize its effects on the affordability of assisted reproductive
      technology. Methods: This randomized controlled study was conducted at the
      Fertility Unit of Tanta Educational Hospital of Tanta University, the Egyptian
      Consultants' Fertility Center, and the Qurrat Aien Fertility Center, from January
      1 to June 30, 2017. Patients' demographic data, stimulation protocol, costs,
      pregnancy rate, and complications were recorded. Patients were randomly allocated
      into two groups: group I (n=61) received 0.125 mg of cetrorelix (the study
      group), and group II (n=62) received 0.25 mg of cetrorelix (the control group).
      Results: The demographic data were comparable regarding age, parity, duration of
      infertility, and body mass index. The dose of recombinant follicle-stimulating
      hormone units required was 2,350.43+/-150.76 IU in group I and 2,366.25+/-140.34
      IU in group II, which was not a significant difference (p=0.548). The duration of
      stimulation, number of retrieved oocytes, and number of developed embryos were
      not significantly different between the groups. The clinical and ongoing
      pregnancy rates likewise did not significantly differ. The cost of
      intracytoplasmic sperm injection per cycle was significantly lower in group I
      than in group II (US $494.66+/-4.079 vs. US $649.677+/-43.637). Conclusion:
      Reduction of the cetrorelix dose in the antagonist protocol was not associated
      with any significant difference either in the number of oocytes retrieved or in
      the pregnancy rate. Moreover, it was more economically feasible for patients in a
      low-resource country.

PMID- 29376022
TI  - Editorial: How Reproductive History Influences Our Breast Cancer Risk.

PMID- 29376024
TI  - Editorial: Murine Models of Leukemia and Lymphoma.

PMID- 29376023
TI  - Glutamine Transport and Mitochondrial Metabolism in Cancer Cell Growth.
AB  - The concept that cancer is a metabolic disease is now well acknowledged: many
      cancer cell types rely mostly on glucose and some amino acids, especially
      glutamine for energy supply. These findings were corroborated by overexpression
      of plasma membrane nutrient transporters, such as the glucose transporters
      (GLUTs) and some amino acid transporters such as ASCT2, LAT1, and ATB0,+, which
      became promising targets for pharmacological intervention. On the basis of their
      sodium-dependent transport modes, ASCT2 and ATB0+ have the capacity to sustain
      glutamine need of cancer cells; while LAT1, which is sodium independent will have
      the role of providing cancer cells with some amino acids with plausible signaling
      roles. According to the metabolic reprogramming of many types of cancer cells,
      glucose is mainly catabolized by aerobic glycolysis in tumors, while the fate of
      Glutamine is completed at mitochondrial level where the enzyme Glutaminase
      converts Glutamine to Glutamate. Glutamine rewiring in cancer cells is
      heterogeneous. For example, Glutamate is converted to alpha-Ketoglutarate giving
      rise to a truncated form of Krebs cycle. This reprogrammed pathway leads to the
      production of ATP mainly at substrate level and regeneration of reducing
      equivalents needed for cells growth, redox balance, and metabolic energy. Few
      studies on hypothetical mitochondrial transporter for Glutamine are reported and
      indirect evidences suggested its presence. Pharmacological compounds able to
      inhibit Glutamine metabolism may represent novel drugs for cancer treatments.
      Interestingly, well acknowledged targets for drugs are the Glutamine transporters
      of plasma membrane and the key enzyme Glutaminase.

PMID- 29376025
TI  - Deep Deconvolutional Neural Network for Target Segmentation of Nasopharyngeal
      Cancer in Planning Computed Tomography Images.
AB  - Background: Radiotherapy is one of the main treatment methods for nasopharyngeal
      carcinoma (NPC). It requires exact delineation of the nasopharynx gross tumor
      volume (GTVnx), the metastatic lymph node gross tumor volume (GTVnd), the
      clinical target volume (CTV), and organs at risk in the planning computed
      tomography images. However, this task is time-consuming and operator dependent.
      In the present study, we developed an end-to-end deep deconvolutional neural
      network (DDNN) for segmentation of these targets. Methods: The proposed DDNN is
      an end-to-end architecture enabling fast training and testing. It consists of two
      important components: an encoder network and a decoder network. The encoder
      network was used to extract the visual features of a medical image and the
      decoder network was used to recover the original resolution by deploying
      deconvolution. A total of 230 patients diagnosed with NPC stage I or stage II
      were included in this study. Data from 184 patients were chosen randomly as a
      training set to adjust the parameters of DDNN, and the remaining 46 patients were
      the test set to assess the performance of the model. The Dice similarity
      coefficient (DSC) was used to quantify the segmentation results of the GTVnx,
      GTVnd, and CTV. In addition, the performance of DDNN was compared with the VGG-16
      model. Results: The proposed DDNN method outperformed the VGG-16 in all the
      segmentation. The mean DSC values of DDNN were 80.9% for GTVnx, 62.3% for the
      GTVnd, and 82.6% for CTV, whereas VGG-16 obtained 72.3, 33.7, and 73.7% for the
      DSC values, respectively. Conclusion: DDNN can be used to segment the GTVnx and
      CTV accurately. The accuracy for the GTVnd segmentation was relatively low due to
      the considerable differences in its shape, volume, and location among patients.
      The accuracy is expected to increase with more training data and combination of
      MR images. In conclusion, DDNN has the potential to improve the consistency of
      contouring and streamline radiotherapy workflows, but careful human review and a
      considerable amount of editing will be required.

PMID- 29376026
TI  - Planning Today for Tomorrow's Research: Analysis of Factors Influencing
      Participation in a Pediatric Cancer Research Biorepository.
AB  - Background: Biobanks have become a powerful tool that fosters biomedical
      research. The success of biobanks depends upon people's perception and
      willingness to donate their samples for research. This is the first biorepository
      in Egypt, hence, little is known about the beliefs and attitudes of parents
      toward participation. Aim: To investigate the level of willingness of Egyptians
      to donate samples of their children and themselves for research and the different
      factors influencing participation. Materials and methods: A structured
      questionnaire was designed covering multiple items expected to affect the
      enrollment decision. This was conducted in-person, and data collected included
      demographic data, socioeconomic, and educational level. In addition, in the case
      of refusal, participants were asked about reasons behind their decision. Results:
      Only about 3.1% of patients have not been enrolled in the project, and 0.3% have
      withdrawn. Three demographic factors were found having disparate trends in the
      decision-making process to participate or not: father's education (p = 0.0001),
      mother's education (p = 0.0001), and father's age (p = 0.034). Conclusion:
      Egyptian parents were willing to donate their samples as well as their children's
      samples in our research biorepository. The idea of participation was presented in
      an interview during which the consent form was explained in a comprehensive
      transparent way allowing participants the right to refuse or withdraw at any
      time. Still, different communication approaches are needed with older, more
      highly educated parents to encourage them to participate.

PMID- 29376028
TI  - Pediatric Anaplastic Embryonal Rhabdomyosarcoma: Targeted Therapy Guided by
      Genetic Analysis and a Patient-Derived Xenograft Study.
AB  - Therapy for rhabdomyosarcoma (RMS) has generally been limited to combinations of
      conventional cytotoxic agents similar to regimens originally developed in the
      late 1960s. Recently, identification of molecular alterations through next
      generation sequencing of individual tumor specimens has facilitated the use of
      more targeted therapeutic approaches for various malignancies. Such targeted
      therapies have revolutionized treatment for some cancer types. However,
      malignancies common in children, thus far, have been less amenable to such
      targeted therapies. This report describes the clinical course of an 8-year-old
      female with embryonal RMS having anaplastic features. This patient experienced
      multiple relapses after receiving various established and experimental therapies.
      Genomic testing of this RMS subtype revealed mutations in BCOR, ARID1A, and SETD2
      genes, each of which contributes to epigenetic regulation and interacts with or
      modifies the activity of histone deacetylases (HDAC). Based on these findings,
      the patient was treated with the HDAC inhibitor vorinostat as a single agent. The
      tumor responded transiently followed by subsequent disease progression. We also
      examined the efficacy of vorinostat in a patient-derived xenograft (PDX) model
      developed using tumor tissue obtained from the patient's most recent tumor
      resection. The antitumor activity of vorinostat observed with the PDX model
      reflected clinical observations in that obvious areas of tumor necrosis were
      evident following exposure to vorinostat. Histologic sections of tumors harvested
      from PDX tumor-bearing mice treated with vorinostat demonstrated induction of
      necrosis by this agent. We propose that the evaluation of clinical efficacy in
      this type of preclinical model merits further evaluation to determine if PDX
      models predict tumor sensitivity to specific agents and/or combination therapies.

PMID- 29376027
TI  - Efficacy of Complementary Therapies in the Quality of Life of Breast Cancer
      Survivors.
AB  - Breast cancer (BC) is the most common cancer diagnosed in women and the second
      most common cancer overall, ranking as the fifth cause of death from cancer. The
      chronicity of the disease produces long-term physiological and psychological
      manifestations, which adversely affect the quality of life of the individual. The
      primary treatment while managing cancer presents with various debilitating side
      effects. With the recent advances in treatment techniques that have improved the
      survival rate, patients suffer from continuing posttreatment complications.
      Patients seem to cope well with the stress of treatment of BC and sustain a
      normal life; however, the deterioration in physical well-being makes the patient
      functionally inefficient. Exercise has been proven to be an effective, safe, and
      feasible tool in combating the adverse effects of treatment, prevents
      complications and decreases the risk of BC-specific mortality. This review
      briefly presents an overview of the burden of the disease and its management
      strategies. Owing to the heterogeneity of the population and the multitude of
      therapies they receive, the response of each patient to treatment is different
      and so is the magnitude of adverse effects. The review discusses the late
      sequelae following treatment and evidence supporting the role of physical
      activity in their management. In conclusion, there is a need for personalized
      physical activity plans to be developed to suit the individual and their
      circumstances.

PMID- 29376029
TI  - Hijacking of the Host Ubiquitin Network by Legionella pneumophila.
AB  - Protein ubiquitination is critical for regulation of numerous eukaryotic cellular
      processes such as protein homeostasis, cell cycle progression, immune response,
      DNA repair, and vesicular trafficking. Ubiquitination often leads to the
      alteration of protein stability, subcellular localization, or interaction with
      other proteins. Given the importance of ubiquitination in the regulation of host
      immunity, it is not surprising that many infectious agents have evolved
      strategies to interfere with the ubiquitination network with sophisticated
      mechanisms such as functional mimicry. The facultative intracellular pathogen
      Legionella pneumophila is the causative agent of Legionnaires' disease. L.
      pneumophila is phagocytosed by macrophages and is able to replicate within a
      niche called Legionella-containing vacuole (LCV). The biogenesis of LCV is
      dependent upon the Dot/Icm type IV secretion system which delivers more than 330
      effector proteins into host cytosol. The optimal intracellular replication of L.
      pneumophila requires the host ubiquitin-proteasome system. Furthermore, membranes
      of the bacterial phagosome are enriched with ubiquitinated proteins in a way that
      requires its Dot/Icm type IV secretion system, suggesting the involvement of
      effectors in the manipulation of the host ubiquitination machinery. Here we
      summarize recent advances in our understanding of mechanisms exploited by L.
      pneumophila effector proteins to hijack the host ubiquitination pathway.

PMID- 29376030
TI  - Microbial Pre-exposure and Vectorial Competence of Anopheles Mosquitoes.
AB  - Anopheles female mosquitoes can transmit Plasmodium, the malaria parasite. During
      their aquatic life, wild Anopheles mosquito larvae are exposed to a huge
      diversity of microbes present in their breeding sites. Later, adult females often
      take successive blood meals that might also carry different micro-organisms,
      including parasites, bacteria, and viruses. Therefore, prior to Plasmodium
      ingestion, the mosquito biology could be modulated at different life stages by a
      suite of microbes present in larval breeding sites, as well as in the adult
      environment. In this article, we highlight several naturally relevant scenarios
      of Anopheles microbial pre-exposure that we assume might impact mosquito
      vectorial competence for the malaria parasite: (i) larval microbial exposures;
      (ii) protist co-infections; (iii) virus co-infections; and (iv) pathogenic
      bacteria co-infections. In addition, significant behavioral changes in African
      Anopheles vectors have been associated with increasing insecticide resistance. We
      discuss how these ethological modifications may also increase the repertoire of
      microbes to which mosquitoes could be exposed, and that might also influence
      their vectorial competence. Studying Plasmodium-Anopheles interactions in natural
      microbial environments would efficiently contribute to refining the transmission
      risks.

PMID- 29376031
TI  - The Chlamydia pneumoniae Tarp Ortholog CPn0572 Stabilizes Host F-Actin by
      Displacement of Cofilin.
AB  - Pathogenic Chlamydia species force entry into human cells via specific adhesin
      receptor interactions and subsequently secrete effector proteins into the host
      cytoplasm, which in turn modulate host-cell processes to promote infection. One
      such effector, the C. trachomatis Tarp factor, nucleates actin polymerization in
      vitro. Here we show that its C. pneumoniae ortholog, CPn0572, associates with
      actin patches upon bacterial invasion. GFP-CPn0572 ectopically expressed in yeast
      and human cells co-localizes with actin patches and distinctly aberrantly
      thickened and extended actin cables. A 59-aa DUF 1547 (DUF) domain, which
      overlaps with the minimal actin-binding and protein oligomerization fragment
      required for actin nucleation in other Tarp orthologs, is responsible for the
      aberrant actin phenotype in yeast. Interestingly, GFP-CPn0572 in human cells
      associated with and led to the formation of non-actin microfilaments. This
      phenotype is strongly enhanced in human cells expressing the GFP-tagged DUF
      deletion variant (GFP-DeltaDUF). Finally ectopic CPn0572 expression in yeast and
      in-vitro actin filament binding assays, demonstrated that CPn0572 stabilizes pre
      assembled F-actin by displacing and/or inhibiting binding of the actin-severing
      protein cofilin. Remarkably, the DUF domain suffices to displace cofilin from F
      actin. Thus, in addition to its actin-nucleating activities, the C. pneumoniae
      CPn0572 also stabilizes preformed host actin filaments.

PMID- 29376032
TI  - Amoebae, Giant Viruses, and Virophages Make Up a Complex, Multilayered Threesome.
AB  - Viral infection had not been observed for amoebae, until the Acanthamoeba
      polyphaga mimivirus (APMV) was discovered in 2003. APMV belongs to the
      nucleocytoplasmatic large DNA virus (NCLDV) family and infects not only A.
      polyphaga, but also other professional phagocytes. Here, we review the
      Megavirales to give an overview of the current members of the Mimi- and
      Marseilleviridae families and their structural features during amoebal infection.
      We summarize the different steps of their infection cycle in A. polyphaga and
      Acanthamoeba castellani. Furthermore, we dive into the emerging field of
      virophages, which parasitize upon viral factories of the Megavirales family. The
      discovery of virophages in 2008 and research in recent years revealed an
      increasingly complex network of interactions between cell, giant virus, and
      virophage. Virophages seem to be highly abundant in the environment and occupy
      the same niches as the Mimiviridae and their hosts. Establishment of metagenomic
      and co-culture approaches rapidly increased the number of detected virophages
      over the recent years. Genetic interaction of cell and virophage might constitute
      a potent defense machinery against giant viruses and seems to be important for
      survival of the infected cell during mimivirus infections. Nonetheless, the
      molecular events during co-infection and the interactions of cell, giant virus,
      and virophage have not been elucidated, yet. However, the genetic interactions of
      these three, suggest an intricate, multilayered network during amoebal (co
      )infections. Understanding these interactions could elucidate molecular events
      essential for proper viral factory activity and could implicate new ways of
      treating viruses that form viral factories.

PMID- 29376034
TI  - Novel Cysteine Desulfidase CdsB Involved in Releasing Cysteine Repression of
      Toxin Synthesis in Clostridium difficile.
AB  - Clostridium difficile, a major cause of nosocomial diarrhea and pseudomembranous
      colitis, still poses serious health-care challenges. The expression of its two
      main virulence factors, TcdA and TcdB, is reportedly repressed by cysteine, but
      molecular mechanism remains unclear. The cysteine desulfidase CdsB affects the
      virulence and infection progresses of some bacteria. The C. difficile strain 630
      genome encodes a homolog of CdsB, and in the present study, we analyzed its role
      in C. difficile 630Deltaerm by constructing an isogenic ClosTron-based cdsB
      mutant. When C. difficile was cultured in TY broth supplemented with cysteine,
      the cdsB gene was rapidly induced during the exponential growth phase. The
      inactivation of cdsB not only affected the resistance of C. difficile to
      cysteine, but also altered the expression levels of intracellular cysteine
      degrading enzymes and the production of hydrogen sulfide. This suggests that C.
      difficile CdsB is a major inducible cysteine-degrading enzyme. The inactivation
      of the cdsB gene in C. difficile also removed the cysteine-dependent repression
      of toxin production, but failed to remove the Na2S-dependent repression, which
      supports that the cysteine-dependent repression of toxin production is probably
      attributable to the accumulation of cysteine by-products. We also mapped a
      delta54 (SigL)-dependent promoter upstream from the cdsB gene, and cdsB
      expression was not induced in response to cysteine in the cdsR::ermB or
      sigL::ermB strain. Using a reporter gene fusion analysis, we identified the
      necessary promoter sequence for cysteine-dependent cdsB expression. Taken
      together, these results indicate that CdsB is a key inducible cysteine
      desulfidase in C. difficile which is regulated by delta54 and CdsR in response to
      cysteine and that cysteine-dependent regulation of toxin production is closely
      associated with cysteine degradation.

PMID- 29376033
TI  - When Dicty Met Myco, a (Not So) Romantic Story about One Amoeba and Its
      Intracellular Pathogen.
AB  - In recent years, Dictyostelium discoideum has become an important model organism
      to study the cell biology of professional phagocytes. This amoeba not only shares
      many molecular features with mammalian macrophages, but most of its fundamental
      signal transduction pathways are conserved in humans. The broad range of existing
      genetic and biochemical tools, together with its suitability for cell culture and
      live microscopy, make D. discoideum an ideal and versatile laboratory organism.
      In this review, we focus on the use of D. discoideum as a phagocyte model for the
      study of mycobacterial infections, in particular Mycobacterium marinum. We look
      in detail at the intracellular cycle of M. marinum, from its uptake by D.
      discoideum to its active or passive egress into the extracellular medium. In
      addition, we describe the molecular mechanisms that both the mycobacterial
      invader and the amoeboid host have developed to fight against each other, and
      compare and contrast with those developed by mammalian phagocytes. Finally, we
      introduce the methods and specific tools that have been used so far to monitor
      the D. discoideum-M. marinum interaction.

PMID- 29376035
TI  - Ehrlichia chaffeensis TRP32 Nucleomodulin Function and Localization Is Regulated
      by NEDD4L-Mediated Ubiquitination.
AB  - Ehrlichia chaffeensis is an obligately intracellular bacterium that reprograms
      the mononuclear phagocyte through diverse effector-host interactions to modulate
      various host cell processes. In a previous study, we reported that the E.
      chaffeensis nucleomodulin TRP32 regulates transcription of host genes in several
      biologically relevant categories, including cell differentiation and
      proliferation. In this study, we investigate the effect of ubiquitination on
      TRP32 function and localization within the host cell. TRP32 is both mono- and
      polyubiquitinated on multiple lysine residues during infection and when
      ectopically expressed. Despite lacking a canonical PPxY motif, TRP32 interacted
      with, and was modified by the human HECT E3 ubiquitin (Ub) ligase NEDD4L. TRP32
      ubiquitination was not by K48-linked polyUb chains, nor was it degraded by the
      proteasome; however, TRP32 was modified by K63-linked polyUb chains detected both
      in the cytosol and nucleus. HECT ligase inhibitor, heclin, altered the subnuclear
      localization of ectopically expressed TRP32 from a diffuse nuclear pattern to a
      lacy, punctate pattern with TRP32 distributed around the periphery of the nucleus
      and nucleoli. When a TRP32 lysine null (K-null) mutant was ectopically expressed,
      it exhibited a similar phenotype as single lysine mutants (K63R, K93R, and
      K123R). However, the K-null mutant showed increased amounts of cytoplasmic TRP32
      compared to single lysine mutants or heclin-treated cells ectopically expressing
      TRP32. These alterations in localization corresponded to changes in TRP32
      transcriptional repressor function with heclin-treated and single lysine mutants
      unable to repress transcription of a TRP32 target genes in a luciferase assay.

PMID- 29376036
TI  - The Global Acetylome of the Human Pathogen Vibrio cholerae V52 Reveals Lysine
      Acetylation of Major Transcriptional Regulators.
AB  - Protein lysine acetylation is recognized as an important reversible post
      translational modification in all domains of life. While its primary roles appear
      to reside in metabolic processes, lysine acetylation has also been implicated in
      regulating pathogenesis in bacteria. Several global lysine acetylome analyses
      have been carried out in various bacteria, but thus far there have been no
      reports of lysine acetylation taking place in the important human pathogen Vibrio
      cholerae. In this study, we analyzed the lysine acetylproteome of the human
      pathogen V. cholerae V52. By applying a combination of immuno-enrichment of
      acetylated peptides and high resolution mass spectrometry, we identified 3,402
      acetylation sites on 1,240 proteins. Of the acetylated proteins, more than half
      were acetylated on two or more sites. As reported for other bacteria, we observed
      that many of the acetylated proteins were involved in metabolic and cellular
      processes and there was an over-representation of acetylated proteins involved in
      protein synthesis. Of interest, we demonstrated that many global transcription
      factors such as CRP, H-NS, IHF, Lrp and RpoN as well as transcription factors
      AphB, TcpP, and PhoB involved in direct regulation of virulence in V. cholerae
      were acetylated. In conclusion, this is the first global protein lysine acetylome
      analysis of V. cholerae and should constitute a valuable resource for in-depth
      studies of the impact of lysine acetylation in pathogenesis and other cellular
      processes.

PMID- 29376037
TI  - Emerging Role of Proteases in the Pathogenesis of Chronic Rhinosinusitis with
      Nasal Polyps.
AB  - Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous upper airway
      disease with multiple etiologies. Clinically, CRSwNP can be classified into
      either eosinophilic or non-eosinophilic subtypes. The eosinophilic phenotype of
      CRSwNP is widely thought to be highly associated with recurrence of nasal polyps
      or surgical failure. Epithelial cells have a crucial role in the development of
      Th2-biased airway diseases. Recent studies have shown that a wide range of
      external stimuli such as allergens and microorganisms can elicit the release of
      epithelial-derived Th2-driving cytokines and chemokines. Protease activity is a
      feature common to these multiple environmental insults and there is growing
      evidence for the concept that an imbalance of proteases and protease inhibitors
      in the epithelial barrier leads to both the initiation and maintenance of chronic
      eosinophilic airway inflammation. In this review, we analyze recent work on the
      role of proteases in the development of the sinonasal mucosal type 2 immune
      response with an emphasis on the molecular pathways promoting adaptive Th2 cell
      immunity.

PMID- 29376038
TI  - Comparative Whole-Genomic Analysis of an Ancient L2 Lineage Mycobacterium
      tuberculosis Reveals a Novel Phylogenetic Clade and Common Genetic Determinants
      of Hypervirulent Strains.
AB  - Background: Development of improved therapeutics against tuberculosis (TB) is
      hindered by an inadequate understanding of the relationship between disease
      severity and genetic diversity of its causative agent, Mycobacterium
      tuberculosis. We previously isolated a hypervirulent M. tuberculosis strain H112
      from an HIV-negative patient with an aggressive disease progression from
      pulmonary TB to tuberculous meningitis-the most severe manifestation of
      tuberculosis. Human macrophage challenge experiment demonstrated that the strain
      H112 exhibited significantly better intracellular survivability and induced lower
      level of TNF-alpha than the reference virulent strain H37Rv and other 123
      clinical isolates. Aim: The present study aimed to identify the potential genetic
      determinants of mycobacterial virulence that were common to strain H112 and
      hypervirulent M. tuberculosis strains of the same phylogenetic clade isolated in
      other global regions. Methods: A low-virulent M. tuberculosis strain H54 which
      belonged to the same phylogenetic lineage (L2) as strain H112 was selected from a
      collection of 115 clinical isolates. Both H112 and H54 were whole-genome
      sequenced using PacBio sequencing technology. A comparative genomics approach was
      adopted to identify mutations present in strain H112 but absent in strain H54.
      Subsequently, an extensive phylogenetic analysis was conducted by including all
      publically available M. tuberculosis genomes. Single-nucleotide-polymorphisms
      (SNPs) and structural variations (SVs) common to hypervirulent strains in the
      global collection of genomes were considered as potential genetic determinants of
      hypervirulence. Results:Sequencing data revealed that both H112 and H54 were
      identified as members of the same sub-lineage L2.2.1. After excluding the lineage
      related mutations shared between H112 and H54, we analyzed the phylogenetic
      relatedness of H112 with global collection of M. tuberculosis genomes (n =
      4,338), and identified a novel phylogenetic clade in which four hypervirulent
      strains isolated from geographically diverse regions were clustered together. All
      hypervirulent strains in the clade shared 12 SNPs and 5 SVs with H112, including
      those affecting key virulence-associated loci, notably, a deleterious SNP (rv0178
      p. D150E) within mce1 operon and an intergenic deletion (854259_ 854261delCC) in
      close-proximity to phoP. Conclusion: The present study identified common genetic
      factors in a novel phylogenetic clade of hypervirulent M. tuberculosis. The
      causative role of these mutations in mycobacterial virulence should be validated
      in future study.

PMID- 29376040
TI  - Comment on "Advanced Hepatic Fibrosis in Fatty Liver Disease Linked to
      Hyperplastic Colonic Polyp".

PMID- 29376039
TI  - Sinus Microanatomy and Microbiota in a Rabbit Model of Rhinosinusitis.
AB  - Background: Rabbits are useful for preclinical studies of sinusitis because of
      similar physiologic features to humans. The objective of this study is to develop
      a rabbit model of sinusitis that permits assessment of microanatomy and sampling
      for evaluating shifts in the sinus microbiota during the development of sinusitis
      and to test how the mucociliary clearance (MCC) defect might lead to dysbiosis
      and chronic rhinosinusitis (CRS). Methods: Generation of CRS was accomplished
      with an insertion of a sterile sponge into the left middle meatus of New Zealand
      white rabbits (n = 9) for 2 weeks. After sponge removal, 4 rabbits were observed
      for another 10 weeks and evaluated for CRS using endoscopy, microCT,
      visualization of the functional micro-anatomy by micro-optical coherence
      tomography (MUOCT), and histopathological analysis of the sinus mucosa. Samples
      were taken from the left middle meatus and submitted for microbiome analysis.
      Results: CT demonstrated opacification of all left sinuses at 2 weeks in all
      rabbits (n = 9), which persisted in animals followed for another 12 weeks (n =
      4). Histology at week 2 showed mostly neutrophils. On week 14, significant
      infiltration of plasma cells and lymphocytes was noted with increased submucosal
      glands compared to controls (p = 0.02). Functional microanatomy at 2 weeks showed
      diminished periciliary layer (PCL) depth (p < 0.0001) and mucus transport (p =
      0.0044) compared to controls despite a thick mucus layer. By 12 weeks, the
      thickened mucus layer was resolved but PCL depletion persisted in addition to
      decreased ciliary beat frequency (CBF; p < 0.0001). The mucin fermenting microbes
      (Lactobacillales, Bacteroidales) dominated on week 2 and there was a significant
      shift to potential pathogens (e.g., Pseudomonas, Burkholderia) by week 14
      compared to both controls and the acute phase (p < 0.05). Conclusion: We
      anticipate this reproducible model will provide a means for identifying
      underlying mechanisms of airway-surface liquid (ASL) depletion and fundamental
      changes in sinus microbial communities that contribute to the development of CRS.
      The rabbit model of sinusitis exhibited diminished PCL depth with delayed mucus
      transport and significant alterations and shift in the sinus microbiome during
      the development of chronic inflammation.

PMID- 29376041
TI  - Skin Biomarkers for Cystic Fibrosis: A Potential Non-Invasive Approach for
      Patient Screening.
AB  - Background: Cystic fibrosis (CF) is a disabling genetic disease with an increased
      prevalence in European heritage populations. Currently, the most used technique
      for collection of CF samples and diagnosis is provided through uncomfortable
      tests, with uncertain results, mostly based on chloride concentration in sweat.
      Since CF mutation induces many metabolic changes in patients, exploring these
      alterations might be an alternative to visualize potential biomarkers that could
      be used as interesting tools for further diagnostic upgrade, prioritizing
      simplicity, low cost, and quickness. Methods: This contribution describes an
      accurate strategy to provide potential biomarkers related to CF, which may be
      understood as a potential tool for new diagnostic approaches and/or for
      monitoring disease evolution. Therefore, the present proposal consists of using
      skin imprints on silica plates as a way of sample collection, followed by direct
      infusion high-resolution mass spectrometry and multivariate data analysis,
      intending to identify metabolic changes in skin composition of CF patients.
      Results: Metabolomics analysis allowed identifying chemical markers that can be
      traced back to CF in patients' skin imprints, differently from control subjects.
      Seven chemical markers from several molecular classes were elected, represented
      by bile acids, a glutaric acid derivative, thyrotropin-releasing hormone, an
      inflammatory mediator, a phosphatidic acid, and diacylglycerol isomers, all
      reflecting metabolic disturbances that occur due to of CF. Conclusion: The
      comfortable method of sample collection combined with the identified set of
      biomarkers represent potential tools that open the range of possibilities to
      manage CF and follow the disease evolution. This exploratory approach points to
      new perspectives about the development of diagnostic assay using biomarkers and
      the management CF.

PMID- 29376043
TI  - Editorial: Neuro-Development and Psychological Issues in Congenital Heart
      Defects.

PMID- 29376042
TI  - Suggested Mechanisms of Tracheal Occlusion Mediated Accelerated Fetal Lung
      Growth: A Case for Heterogeneous Topological Zones.
AB  - In this article, we report an up-to-date summary on tracheal occlusion (TO) as an
      approach to drive accelerated lung growth and strive to review the different
      maternal- and fetal-derived local and systemic signals and mechanisms that may
      play a significant biological role in lung growth and formation of heterogeneous
      topological zones following TO. Pulmonary hypoplasia is a condition whereby
      branching morphogenesis and embryonic pulmonary vascular development are globally
      affected and is classically seen in congenital diaphragmatic hernia. TO is an
      innovative approach aimed at driving accelerated lung growth in the most severe
      forms of diaphragmatic hernia and has been shown to result in improved neonatal
      outcomes. Currently, most research on mechanisms of TO-induced lung growth is
      focused on mechanical forces and is viewed from the perspective of homogeneous
      changes within the lung. We suggest that the key principle in understanding
      changes in fetal lungs after TO is taking into account formation of unique
      variable topological zones. Following TO, fetal lungs might temporarily look like
      a dynamically changing topologic mosaic with varying proliferation rates,
      dissimilar scale of vasculogenesis, diverse patterns of lung tissue damage,
      variable metabolic landscape, and different structures. The reasons for this
      dynamic topological mosaic pattern may include distinct degree of increased
      hydrostatic pressure in different parts of the lung, dissimilar degree of tissue
      stress/damage and responses to this damage, and incomparable patterns of altered
      lung zones with variable response to systemic maternal and fetal factors, among
      others. The local interaction between these factors and their accompanying
      processes in addition to the potential role of other systemic factors might lead
      to formation of a common vector of biological response unique to each zone. The
      study of the interaction between various networks formed after TO (action of
      mechanical forces, activation of mucosal mast cells, production and secretion of
      damage-associated molecular pattern substances, low-grade local pulmonary
      inflammation, and cardiac contraction-induced periodic agitation of lung tissue,
      among others) will bring us closer to an appreciation of the biological
      phenomenon of topological heterogeneity within the fetal lungs.

PMID- 29376044
TI  - The Genetic Basis of Type 2 Diabetes in Hispanics and Latin Americans: Challenges
      and Opportunities.
AB  - Type 2 diabetes (T2D) affects 415 million people worldwide, and has a much higher
      prevalence in Hispanics (16.9%), compared to non-Hispanic whites (10.2%). Genome
      wide association studies and whole-genome and whole-exome sequencing studies have
      discovered more than 100 genetic regions associated with modified risk for T2D.
      However, the identified genetic factors explain a very small fraction of the
      estimated heritability. Until recently, little attention has been put in studying
      other non European populations that suffer from a higher burden of T2D, such as
      Hispanics/Latinos. In the past few years, genetic studies in Hispanic populations
      have started to provide new insights into the genetic architecture of T2D in this
      ancestry group. Of note, several genetic variants that are absent or very rare in
      non-Hispanic populations but more common in Hispanics have shown from moderate to
      strong association with T2D and have provided new insights into the biology of
      T2D, which may be ultimately useful for developing novel therapeutic strategies
      applicable to all populations. Studying diverse populations can also improve the
      ability to find the causal variants in known T2D loci by a multi-ancestry fine
      mapping approach, which leverages the different patterns of linkage
      disequilibrium between the causal and the ascertained genetic variants. In this
      mini-review, we summarize the main genetic findings discovered in Hispanics and
      discuss the limitations and challenges of performing genetic studies in these
      populations. Finally, we present possible next steps to make studies in Latino
      populations more valuable in providing a deeper understanding of T2D and
      anticipate their future application to the development of predictive and
      preventive medicine and personalized therapies.

PMID- 29376045
TI  - Virtual Reality As a Training Tool to Treat Physical Inactivity in Children.
AB  - Lack of adequate physical activity in children is an epidemic that can result in
      obesity and other poor health outcomes across the lifespan. Physical activity
      interventions focused on motor skill competence continue to be developed, but
      some interventions, such as neuromuscular training (NMT), may be limited in how
      early they can be implemented due to dependence on the child's level of cognitive
      and perceptual-motor development. Early implementation of motor-rich activities
      that support motor skill development in children is critical for the development
      of healthy levels of physical activity that carry through into adulthood. Virtual
      reality (VR) training may be beneficial in this regard. VR training, when
      grounded in an information-based theory of perceptual-motor behavior that
      modifies the visual information in the virtual world, can promote early
      development of motor skills in youth akin to more natural, real-world development
      as opposed to strictly formalized training. This approach can be tailored to the
      individual child and training scenarios can increase in complexity as the child
      develops. Ultimately, training in VR may help serve as a precursor to "real
      world" NMT, and once the child reaches the appropriate training age can also
      augment more complex NMT regimens performed outside of the virtual environment.

PMID- 29376046
TI  - Stages of Biological Development across Age: An Analysis of Canadian Health
      Measure Survey 2007-2011.
AB  - Introduction: The stages of biological development are not clearly defined
      despite the fact that they have been used to refer to concepts such as
      adolescence and aging. This study aimed to (1) propose and test a framework to
      search for stages of representative components and determine stages of stability
      and transition, (2) identify stages of biological development based on health
      questionnaire and biomarker data, and (3) interpret the major trajectories in a
      health and biomarker database. Methods: This study analyzed the data on the
      Canadian Health Measures Survey (CHMS) interviewees from cycle 1 to 3 (2007-2013)
      in Canada. We selected 282 variables containing information from questionnaire
      and on biomarkers after removing redundant variables based on high correlation.
      Fifty-nine nominal variables were replaced by 122 binominal variables, leaving
      345 variables for analysis. Principal component (PC) analysis was conducted to
      summarize the data and the loadings were used to interpret the PCs. A stable
      stage was assumed to be the age groups without significantly different values of
      PCs. Results: The CHMS interviewed 16,340 Canadians. Of all, 51.25% were female.
      The age ranged from 6 to 79 years (mean = 34.41 years, 95% CI = 34.74-34.08). The
      proportions of total variance explained by the first three PCs were 12.14, 4.03,
      and 3.19%, respectively. The differences of the first PC were not significant,
      especially between age 22 and 33, 34 and 40, 41 and 45, 46 and 71, and 72 and 79
      years (adjusted p > 0.05 for all). The leading variable, in terms of the variance
      contributed to PC1, was time spent in physical activities, followed by variables
      related to alcohol consumption, and smoking. The 13 leading contributors to PC2
      variances were all lung function measures. Discussion and conclusion: There are
      stages of stability and transition across all age groups based on the first PCs.
      The first and second PCs are related to physical development and lung function.
      The identification of stable stages is the first step to understanding how human
      biology develops in a population perspective and will be important for research
      that relies on a research population with similar characteristics to draw samples
      for observation or intervention.

PMID- 29376047
TI  - Future Perfect? The Future of the Social Sciences in Public Health.
AB  - This is a critical and perhaps unprecedented time for the social sciences in
      public health. While there are many opportunities for the social sciences to
      continue making transformative contributions to improve population health, there
      are significant challenges in doing so, particularly in a rapidly changing
      political landscape. Such challenges are both external (e.g., congressional calls
      for reducing social science funding) and internal (e.g., scholars criticizing the
      social sciences for being stagnant and siloed). This paper highlights four key
      tensions that the field is grappling with and that have direct implications for
      how to train the next generation of social scientists in public health. We also
      discuss how departmental and institutional decisions made in response to these
      tensions will determine how the social sciences in public health are ultimately
      recognized, sustained, and advanced.

PMID- 29376048
TI  - An Evaluation of an eHealth Tool Designed to Improve College Students' Label
      Reading Skills and Feelings of Empowerment to Choose Healthful Foods.
AB  - Objective: College students are at risk for poor dietary choices. New skills can
      empower individuals to adopt healthful behaviors, yet eHealth tools designed to
      develop food-choice skills, such as label-reading skills, are uncommon. We
      investigated the effects of web-based label-reading training on college students'
      perceptions of healthful food-choice empowerment. Methods: Students completed
      label-reading training in which they practiced selecting the more healthful food
      using nutrition labels. We examined improvements in label-reading accuracy
      (correct healthfulness decisions) and perceptions of empowerment, using a 6-item
      scale. Repeated measures ANOVAs and paired-samples t-tests were used to examine
      changes in accuracy and empowerment across the training session. Results: In
      addition to increases in label-reading accuracy with training, we found increases
      in healthful food-choice empowerment scores. Specifically, the proportion of
      correct (i.e., more healthful) food choices increased across the three blocks of
      practice (p = 0.04) and food-choice empowerment scores were about 7.5% higher on
      average after training (p < 0.001). Conclusion and implications: Label-reading
      training was associated with increased feelings of empowerment associated with
      making healthful food choices. Skill focused eHealth tools may offer an important
      avenue for motivating behavior change through skill development.

PMID- 29376049
TI  - Meta-Analysis of Aedes aegypti Expression Datasets: Comparing Virus Infection and
      Blood-Fed Transcriptomes to Identify Markers of Virus Presence.
AB  - The mosquito Aedes aegypti (L.) is vector of several arboviruses including
      dengue, yellow fever, chikungunya, and more recently zika. Previous
      transcriptomic studies have been performed to elucidate altered pathways in
      response to viral infection. However, the intrinsic coupling between alimentation
      and infection were unappreciated in these studies. Feeding is required for the
      initial mosquito contact with the virus and these events are highly dependent.
      Addressing this relationship, we reinterrogated datasets of virus-infected
      mosquitoes with two different diet schemes (fed and unfed mosquitoes), evaluating
      the metabolic cross-talk during both processes. We constructed coexpression
      networks with the differentially expressed genes of these comparison: virus
      infected versus blood-fed mosquitoes and virus-infected versus unfed mosquitoes.
      Our analysis identified one module with 110 genes that correlated with infection
      status (representing ~0.7% of the A. aegypti genome). Furthermore, we performed a
      machine-learning approach and summarized the infection status using only four
      genes (AAEL012128, AAEL014210, AAEL002477, and AAEL005350). While three of the
      four genes were annotated as hypothetical proteins, AAEL012128 gene is a membrane
      amino acid transporter correlated with viral envelope binding. This gene alone is
      able to discriminate all infected samples and thus should have a key role to
      discriminate viral infection in the A. aegypti mosquito. Moreover, validation
      using external datasets found this gene as differentially expressed in four
      transcriptomic experiments. Therefore, these genes may serve as a proxy of viral
      infection in the mosquito and the others 106 identified genes provides a
      framework to future studies.

PMID- 29376051
TI  - Melatonin and the Prevention and Management of Delirium: A Scoping Study.
AB  - Background: The therapeutic benefit of melatonin in the prevention and treatment
      of delirium is uncertain. Objective: To perform a scoping study to describe the
      existing literature regarding the use of melatonin and ramelteon in the
      prevention and treatment of delirium. Methods: We performed a scoping study using
      the Arksey and O'Malley framework to explore our objective. Two independent
      panels searched MEDLINE, OVID, EMBASE, PubMed, Google Scholar, and Cochrane
      Library for relevant articles up to November 2017 describing the use of melatonin
      and ramelteon in the prevention or management of delirium. We extracted relevant
      summary data from the studies and attempted to draw conclusion regarding benefit.
      Results: We summarized evidence from 20 relevant articles. There were a total of
      nine articles: five randomized controlled trials (RCTs), two retrospective
      medical record reviews, one non-randomized observational study, and one case
      report describing the role of either melatonin or ramelteon in preventing
      delirium. There were a total of 11 studies studying the role of either melatonin
      or ramelteon in the management of established delirium. None of these were RCT
      and were predominantly case series and case reports. Four of the five trials
      studying the effect of melatonin analogs in preventing delirium reported a
      beneficial effect but study heterogeneity limited any broad recommendations.
      Similarly, the lack of any well-designed trials limits any recommendations
      regarding the effect of melatonin analogs in treating delirium. Conclusion:
      Large, well-designed clinical trials are required to explore the potential
      beneficial effects of melatonin and ramelteon on delirium prevention and
      management.

PMID- 29376052
TI  - Functional Capacity and Levels of Physical Activity in Aging: A 3-Year Follow-up.
AB  - Over the last decades, the world elderly population has increased exponentially
      and this tendency will continue during the coming years; from 2000 to 2050,
      people over 60 will double and those over 80 will quadruple. Loss of independence
      occurs as people age due to mobility restrictions, frailty, and decreased
      functional fitness and cognitive abilities. Evidence has shown that appropriate
      programs and policies contribute to keep older adults healthy and independent
      over time. The purpose of this chapter is to report the results of our 3-year
      follow-up study designed to characterize functional physical fitness in a sample
      of Portuguese community-dwelling older adults to propose a set of functional
      parameters that decline the most. We studied a group of 43 elderly people, aged
      60 and over. Variables assessed on the participants were anthropometric
      measurements, functional capacity with the Senior Fitness Test battery (muscle
      strength, aerobic endurance, flexibility, agility, and dynamic balance), handgrip
      strength, levels of physical activity, and balance. Three years after the first
      assessment, a second assessment of the same variables was conducted. We analyzed
      what were the variables that, for this group, were related with a healthier aging
      and the relation with different physical activity levels. Our study showed that
      the distance covered in 6-min walk test and handgrip strength seem to explain a
      great amount of variability on functional variables that have changed on this
      period (68% of balance, lower and upper functional strength, respectively) and
      the active participants showed less decrements with aging in anthropometric and
      functional variables than those inactive or insufficiently active (p < 0.05).
      Greater importance should be given to prescription of exercise targeting older
      adults and, specifically, walking and manual activities should be given more
      attention as components of a community exercise program.

PMID- 29376050
TI  - Nuclear Envelope-Associated Chromosome Dynamics during Meiotic Prophase I.
AB  - Chromosome dynamics during meiotic prophase I are associated with a series of
      major events such as chromosomal reorganization and condensation,
      pairing/synapsis and recombination of the homologs, and chromosome movements at
      the nuclear envelope (NE). The NE is the barrier separating the nucleus from the
      cytoplasm and thus plays a central role in NE-associated chromosomal movements
      during meiosis. Previous studies have shown in various species that NE-linked
      chromosome dynamics are actually driven by the cytoskeleton. The linker of
      nucleoskeleton and cytoskeleton (LINC) complexes are important constituents of
      the NE that facilitate in the transfer of cytoskeletal forces across the NE to
      individual chromosomes. The LINCs consist of the inner and outer NE proteins
      Sad1/UNC-84 (SUN), and Klarsicht/Anc-1/Syne (KASH) domain proteins. Meiosis
      specific adaptations of the LINC components and unique modifications of the NE
      are required during chromosomal movements. Nonetheless, the actual role of the NE
      in chromosomic dynamic movements in plants remains elusive. This review
      summarizes the findings of recent studies on meiosis-specific constituents and
      modifications of the NE and corresponding nucleoplasmic/cytoplasmic adaptors
      being involved in NE-associated movement of meiotic chromosomes, as well as
      describes the potential molecular network of transferring cytoplasm-derived
      forces into meiotic chromosomes in model organisms. It helps to gain a better
      understanding of the NE-associated meiotic chromosomal movements in plants.

PMID- 29376054
TI  - Achieving Pregnancy Using Primary Care Interventions to Identify the Fertile
      Window.
AB  - Objective: To determine the effectiveness of achieving pregnancy with focused
      intercourse in the fertile window identified using natural fertility indicators.
      Methods: 24-cycle prospective effectiveness study. Setting: A North American web
      based fertility monitoring service. Participants: 256 North American women aged
      20-43 (mean age 29.2 years) seeking to achieve pregnancy. Intervention:
      Participants identified their fertile window with either electronic hormonal
      fertility monitoring or cervical mucus monitoring, or both, and recorded their
      observations on an online fertility tracking system. Main outcome measures:
      Pregnancies were validated by nurses with an online self-assessed pregnancy
      evaluation form. Survival analysis was used to determine pregnancy rates.
      Results: There were 150 pregnancies among the 256 participants with an overall
      pregnancy rate of 78 per 100 women over 12 menstrual cycles. There were 54
      pregnancies (68%) among the 80 women using the fertility monitor, 11 pregnancies
      (46%) among the 24 women using mucus monitoring, and 90 (63%) among the 143 women
      using both mucus and monitor. The 12-cycle pregnancy rates per 100 women were 83
      (monitor group), 72 (mucus group), and 75 (mucus and monitor group). Pregnancy
      rates reached 100% at 24 cycles of use for those women using the hormonal
      fertility monitor. Conclusion: Use of the hormonal fertility monitor alone seems
      to offer the best natural estimate of the fertile phase of the menstrual cycle
      for women wishing to achieve a pregnancy. Focusing intercourse through 24
      menstrual cycles can be beneficial for achieving pregnancy.

PMID- 29376053
TI  - Metabolic Linkage and Correlations to Storage Capacity in Erythrocytes from
      Glucose 6-Phosphate Dehydrogenase-Deficient Donors.
AB  - Objective: In glucose 6-phosphate dehydrogenase (G6PD) deficiency, decreased
      NADPH regeneration in the pentose phosphate pathway and subnormal levels of
      reduced glutathione result in insufficient antioxidant defense, increased
      susceptibility of red blood cells (RBCs) to oxidative stress, and acute hemolysis
      following exposure to pro-oxidant drugs and infections. Despite the fact that
      redox disequilibrium is a prominent feature of RBC storage lesion, it has been
      reported that the G6PD-deficient RBCs store well, at least in respect to energy
      metabolism, but their overall metabolic phenotypes and molecular linkages to the
      storability profile are scarcely investigated. Methods: We performed UHPLC-MS
      metabolomics analyses of weekly sampled RBC concentrates from G6PD sufficient and
      deficient donors, stored in citrate phosphate dextrose/saline adenine glucose
      mannitol from day 0 to storage day 42, followed by statistical and bioinformatics
      integration of the data. Results: Other than previously reported alterations in
      glycolysis, metabolomics analyses revealed bioactive lipids, free fatty acids,
      bile acids, amino acids, and purines as top variables discriminating RBC
      concentrates for G6PD-deficient donors. Two-way ANOVA showed significant changes
      in the storage-dependent variation in fumarate, one-carbon, and sulfur
      metabolism, glutathione homeostasis, and antioxidant defense (including urate)
      components in G6PD-deficient vs. sufficient donors. The levels of free fatty
      acids and their oxidized derivatives, as well as those of membrane-associated
      plasticizers were significantly lower in G6PD-deficient units in comparison to
      controls. By using the strongest correlations between in vivo and ex vivo
      metabolic and physiological parameters, consecutively present throughout the
      storage period, several interactomes were produced that revealed an interesting
      interplay between redox, energy, and hemolysis variables, which may be further
      associated with donor-specific differences in the post-transfusion performance of
      G6PD-deficient RBCs. Conclusion: The metabolic phenotypes of G6PD-deficient
      donors recapitulate the basic storage lesion profile that leads to loss of
      metabolic linkage and rewiring. Donor-related issues affect the storability of
      RBCs even in the narrow context of this donor subgroup in a way likely relevant
      to transfusion medicine.

PMID- 29376055
TI  - Role of Exosomal MicroRNAs and myomiRs in the Development of Cancer Cachexia
      Associated Muscle Wasting.
AB  - Cachexia is a complex metabolic syndrome that promotes great weight loss, with
      marked muscle mass wasting. In the last years, many efforts have been directed to
      improve the understanding of the mechanisms involved in the disease. This
      syndrome is present in up to 80% of cancer patients and, despite its clinical
      relevance, is underdiagnosed. The orchestration of the molecular and biochemical
      disruptions observed in cachexia is paralleled by inflammation and the
      communication among the different body compartments, including the tumor and the
      skeletal muscle, is still not completely described. One of the mechanisms that
      may be involved in the transduction of the inflammatory signals and the
      activation of catabolic status in muscle is the participation of exosomes
      containing microRNAs (miRNAs) and muscle-specific miRNAs (myomiRs). Exosomes are
      nanovesicles, measuring from 30 to 100 um, and able to carry miRNAs in the
      circulation, promoting cell-cell and tissue-tissue communication in an autocrine,
      paracrine, and endocrine manner. miRNAs transported in exosomes are preserved
      from degradation, while these nanoparticles deliver the cargo to specific cell
      targets, making communication more efficient. Several miRNAs are known to
      modulate inflammatory pathways, to induce metastasis, to mediate cancer
      aggressiveness and even to participate in the regulation of protein synthesis and
      degradation pathways in the skeletal muscle. The aim of this mini-review is to
      describe the present knowledge about the role of exosomal miRNAs and myomiRs in
      the induction of muscle mass wasting in cancer cachexia state and to explain
      which transcription factors, proteins, and pathways are regulated by these
      molecules.

PMID- 29376058
TI  - Animal Welfare and Economic Aspects of Using Nurse Sows in Swedish Pig
      Production.
AB  - The number of born piglets per litter has increased in Swedish pig industry, and
      farmers are struggling to improve piglet survival. A common practice is to make
      litters more equally sized by moving piglets from large litters to smaller to
      make sure that all piglets get an own teat to suckle. Litter equalization is not
      always enough, as many sows have large litters and/or damaged teats, which
      results in an insufficient number of available teats. One way to solve this
      problem is to use nurse sows. A nurse sow raises, and weans, her own piglets
      before receiving a foster litter. The objectives of this study were to address
      how the use of nurse sows affects the welfare of sows and piglets and to explore
      how it impacts the contribution margin of pig production in Sweden. A literature
      search was made to investigate welfare aspects on sows and piglets. As there were
      few published studies on nurse sows, an expert group meeting was organized. In
      order to explore the impact on the contribution margin of pig production, a
      partial budgeting approach with stochastic elements was used for a fictive pig
      farm. Standard templates for calculating costs and benefits were supplemented
      with figures from existing literature and the gathered expert opinions. In
      Sweden, the minimum suckling period is 28 days while published studies involving
      nurse sows, all from outside of Sweden, weaned the piglets at 21 days. A Swedish
      nurse sow will thus get longer lactation period which might increase the risk of
      poor body condition, damaged teats, and shoulder ulcers. This indicates a reduced
      welfare of the sow and may lead to impaired fertility and increased culling risk.
      On the other hand, the piglet mortality could be reduced with the use of nurse
      sows, but the separation and mixing of piglets could be stressful. The partial
      budgeting suggested that the nurse sow system is slightly more profitable (+6,838
      Swedish krona) per farrowing group during one dry and one lactation period
      compared to the conventional system. The result is, however, highly dependent on
      the input values, and welfare aspects were not considered in the calculations.

PMID- 29376057
TI  - High-Sensitivity C-Reactive Protein Is a Predictor of Coronary Microvascular
      Dysfunction in Patients with Ischemic Heart Disease.
AB  - Background: Inflammation and microvascular dysfunction (MVD) are independently
      associated with adverse cardiovascular outcomes in patients with ischemic heart
      disease. This study aimed to assess the relationship between inflammation, MVD,
      and myocardial injury. Methods: Coronary microvascular function was assessed in
      74 patients undergoing percutaneous coronary intervention (PCI) using the index
      of microvascular resistance (IMR) by a pressure-temperature sensor-tipped wire.
      Serum high-sensitivity C-reactive protein (hsCRP) level was quantified by rate
      turbidimetry. Severe MVD was defined as IMR >= 30. Pearson correlation was
      computed to assess the relationships between hsCRP, troponin, and IMR of culprit
      vessel. Predictors of severe MVD were assessed by regression analysis. Results:
      Acute coronary syndromes (ACSs) represented 49% of the total cohort. Study cohort
      was divided into low C-reactive protein (CRP) (hsCRP < 3 mg/L) and high CRP
      (hsCRP >= 3 mg/L) groups. There was higher representation of smokers (78 vs.
      52%), diabetics (39 vs. 18%), and ACS (61 vs. 33%), as well as higher body mass
      index (29.4 +/- 4.6 vs. 27.2 +/- 4.1) in the high CRP group. Pre-PCI and post-PCI
      IMR were significantly elevated in the high CRP group compared to the low CRP
      group (pre-PCI IMR: 29.0 +/- 13.9 vs. 17.4 +/- 11.1, p < 0.0001; post-PCI IMR:
      23.0 +/- 16.8 vs. 15.5 +/- 8.4, p = 0.02). Peak troponin levels were
      significantly raised in the high CRP group (9.96 +/- 17.19 vs. 1.17 +/- 3.00
      MUg/L, p = 0.002). There was a strong positive correlation between hsCRP and pre
      PCI IMR (r = 0.85, p < 0.0001). Pre- and post-PCI IMR levels were correlated with
      peak troponin level (r = 0.45, p < 0.0001; r = 0.33, p = 0.005, respectively).
      Predictors of severe MVD include male gender (OR 3.0), diabetes (OR 3.7), smoking
      history (OR 4.0), ACS presentation (OR 8.5), and hsCRP >= 3 mg/L (OR 5.6).
      Conclusion: hsCRP is a significant predictor of MVD while MVD is associated with
      myocardial injury, supporting the central role of inflammation and MVD in the
      pathophysiology and complications of coronary artery disease. Clinical Trial
      Registration: Australian New Zealand Clinical Trials Registry (ACTRN):
      12617000648325. Universal Trial Number (UTN): U1111-1196-2246.

PMID- 29376056
TI  - Perspectives on Systems Modeling of Human Peripheral Blood Mononuclear Cells.
AB  - Human peripheral blood mononuclear cells (PBMCs) are the key drivers of the
      immune responses. These cells undergo activation, proliferation and
      differentiation into various subsets. During these processes they initiate
      metabolic reprogramming, which is coordinated by specific gene and protein
      activities. PBMCs as a model system have been widely used to study metabolic and
      autoimmune diseases. Herein we review various omics and systems-based approaches
      such as transcriptomics, epigenomics, proteomics, and metabolomics as applied to
      PBMCs, particularly T helper subsets, that unveiled disease markers and the
      underlying mechanisms. We also discuss and emphasize several aspects of T cell
      metabolic modeling in healthy and disease states using genome-scale metabolic
      models.

PMID- 29376059
TI  - A Promising Recombinant Herpesvirus of Turkeys Vaccine Expressing PmpD-N of
      Chlamydia psittaci Based on Elongation Factor-1 Alpha Promoter.
AB  - The obligate intracellular Gram-negative bacterium Chlamydia psittaci often
      causes avian chlamydiosis and influenza-like symptoms in humans. However, the
      commercial subunit C. psittaci vaccine could only provide a partial protection
      against avian chlamydiosis due to poor cellular immune response. In our previous
      study, a recombinant herpesvirus of turkeys (HVT)-delivered vaccine against C.
      psittaci and Marek's disease based on human cytomegalovirus (CMV) promoter (rHVT
      CMV-pmpD) was developed and provided an effective protection against C. psittaci
      disease with less lesions and reduced chlamydial loads. In this study, we
      developed another recombinant HVT vaccine expressing the N-terminal fragment of
      PmpD (PmpD-N) based on human elongation factor-1 alpha (EF-1alpha) promoter (rHVT
      EF-pmpD) by modifying the HVT genome within a bacterial artificial chromosome.
      The related characterization of rHVT-EF-pmpD was evaluated in vitro in comparison
      with that of rHVT-CMV-pmpD. The expression of PmpD-N was determined by western
      blot. Under immunofluorescence microscopy, PmpD-N protein of both two recombinant
      viruses was located in the cytoplasm and on the cell surface. Growth kinetics of
      rHVT-EF-pmpD was comparable to that of rHVT-CMV-pmpD, and the growth rate of rHVT
      EF-pmpD was apparently higher than that of rHVT-CMV-pmpD on 48, 72, and 120 h
      postinfection. Macrophages activated by rHVT-EF-pmpD could produce more nitric
      oxide and IL-6 than that activated by rHVT-CMV-pmpD. In this study, a recombinant
      HVT vaccine expressing PmpD-N based on EF-1alpha promoter was constructed
      successfully, and a further research in vivo was needed to analyze the vaccine
      efficacy.

PMID- 29376060
TI  - Locomotor Behavior of Chickens Anticipating Incline Walking.
AB  - Keel bone damage (KBD) is prevalent in hens raised for egg production, and ramps
      between different tiers in aviaries have potential to reduce the frequency of
      falls resulting in KBD. Effective use of ramps requires modulation of locomotion
      in anticipation of the incline. Inadequate adaptive locomotion may be one
      explanation why domestic layer hens (Gallus gallus domesticus) exhibit high rates
      of KBD. To improve understanding of the capacity of hens to modulate their
      locomotion in anticipation of climbing, we measured the effects of incline angle
      upon the mechanics of the preparatory step before ascending a ramp. Because the
      energetic challenge of climbing increases with slope, we predicted that as angle
      of incline increased, birds during foot contact with the ground before starting
      to climb would increase their peak force and duration of contact and reduce
      variation in center of pressure (COP) under their foot. We tested 20 female
      domestic chickens on ramp inclines at slopes of +0 degrees , +40 degrees , and
      +70 degrees  when birds were 17, 21, 26, 31, and 36 weeks of age. There were
      significantly higher vertical peak ground reaction forces in preparation at the
      steepest slope, and ground contact time increased significantly with each
      increase in ramp angle. Effects upon variation in COP were not apparent;
      likewise, effects of limb length, age, body mass were not significant. Our
      results reveal that domestic chickens are capable of modulating their locomotion
      in response to incline angle.

PMID- 29376062
TI  - Positioning Animal Welfare in the One Health Concept through Evaluation of an
      Animal Welfare Center in Skopje, Macedonia.
AB  - The Animal Welfare Center (AWC) in Macedonia was established in 2009. The
      objectives of the center are animal welfare (AW) education, research, raising
      public awareness of AW, and increasing cooperation between the stakeholders. One
      Health (OH) was not the major focus of the AWC work initially, but, rather, a
      focus that evolved recently. The objective of this study was to evaluate the AWC
      from the OH perspective as an example case for positioning the AW within the
      overall OH concept. Three types of evaluation were performed: (1) assessment of
      OH-ness, by quantitative measurement of the operational and infrastructural
      aspects of the AWC; (2) impact evaluation, by conducting quantitative surveys on
      stakeholders and students; and (3) transdisciplinary evaluation, using semi
      quantitative evaluation of the links of cooperation between the AWC and the
      stakeholders in society by the custom designed CACA (Cooperation, Activities,
      Communication, and Agreement) scoring system. Results for the OH-ness of the AWC
      showed relatively high scores for OH thinking, planning and working and middle
      scores for OH learning and sharing dimensions, i.e., dominance of the operational
      over infrastructural aspects of the AWC. The impact evaluation of the AWC shows
      that familiarity with the OH concept among stakeholders was low (44% of the
      respondents). However, there was a commonality among stakeholder's interest about
      AW and OH. According to the stakeholders' and students' opinions, the influence
      of AW on Animal, Environmental, and Human Health is relatively high (in the upper
      third of the 1-10 scale). The transdisciplinary evaluation of the AWC indicated
      the presence of transdisciplinarity work by the AWC, with a higher focus on the
      Universities and Research Institutions and some governmental institutions, and
      less linked with the Non-Governmental Organizations and Professional Associations
      (Chambers), e.g., the Veterinary Chamber in Macedonia. The evaluations conducted
      indicated that the AWC's work is closely dedicated to improving animal,
      environmental, and human health and has a considerable OH role among the
      stakeholders in the society. This study describes the significant role and
      importance that AW has in OH.

PMID- 29376063
TI  - Hereditary diffuse gastric cancer: One family's story.
AB  - Hereditary diffuse gastric cancer (HDGC) is an inherited form of gastric cancer
      that carries a poor prognosis. Most HDGCs are caused by an autosomal dominant
      genetic mutation in the CDH1 gene, which carries a 70%-80% lifetime risk of
      gastric cancer. Given its submucosal origin, endoscopic surveillance is an
      unreliable means of early detection, and prophylactic gastrectomy is recommended
      for CDH1 positive individuals older than age 20 years. We describe the case of a
      male with recurrent gastric cancer who was diagnosed with HDGC secondary to the
      CDH1 mutation, and we also describe the patient's pedigree and outcomes of
      recommended genetic testing.

PMID- 29376061
TI  - Molecular Characteristics of the Equine Periodontal Ligament.
AB  - The equine periodontal ligament (PDL) is a fibrous connective tissue that covers
      the intra-alveolar parts of the tooth and anchors it to the alveolar bone-it,
      therefore, provides a similar function to a tendinous structure. While several
      studies have considered the formation and structure of tendons, there is
      insufficient information particularly on the molecular composition of the PDL.
      Especially for the equine PDL, there is limited knowledge concerning the
      expression of genes commonly regarded as typical for tendon tissue. In this
      study, the gene expression of, e.g., collagen type 1 alpha 1 (COL1), collagen
      type 3 alpha 1 (COL3), scleraxis (SCX), and fibrocartilage markers was examined
      in the functional mature equine PDL compared with immature and mature equine
      tendon tissue. PDL samples were obtained from incisor, premolar, and molar teeth
      from seven adult horses. Additionally, tendon samples were collected from four
      adult horses and five foals at different sampling locations. Analyses of gene
      expression were performed using real-time quantitative polymerase chain reaction
      (qRT-PCR). Significantly higher expression levels of COL1 and 3 were found in the
      mature equine PDL in comparison with mature tendon, indicating higher rates of
      collagen production and turnover in the mature equine PDL. The expression levels
      of SCX, a specific marker for tenogenic-differentiated cells, were on a similar
      level in functional mature PDL and in mature tendon tissue. Evidence of
      chondrogenic metaplasia, often found in tendon entheses or in pressurized regions
      of tendons, was not found in the mature equine PDL. The obtained results justify
      further experiments focused on the possible use of equine PDL cells for cell
      based regenerative therapies.

PMID- 29376064
TI  - Evaluation of revascularization after total arch replacement in common carotid
      artery occlusion.
AB  - Occlusion of the common carotid artery (CCA) is rare. CCA occlusion (CCAO) can
      present as drowsiness and right hemiplegia related to emboli after total arch
      replacement. Although we selected a follow-up at first because color duplex
      sonography showed retrograde flow from the left external carotid artery to the
      internal carotid artery, this patient had epilepsy and single-photon emission
      computed tomography (SPECT) acquired quantitative results of actual brain
      perfusion and showed insufficient collateral blood flow. To improve brain
      perfusion, we performed a bypass of the left subclavian artery to left CCA
      bypass. Postoperatively, the patient did not have epilepsy and drowsiness. Also,
      right hemiplegia improved enough for him to walk with support. SPECT showed
      increased left cerebral flow (the asymmetry ratio was 71% to 81%). Evaluation of
      the carotid artery with color duplex sonography alone was insufficient when CCAO
      showed retrograde or collateral flow. We should have performed quantitative
      evaluation with SPECT at the same time.

PMID- 29376065
TI  - Haplotype-Contained PCR Products Analysis by Sequencing with Selective
      Restriction of Primer Extension.
AB  - We develop a strategy for haplotype analysis of PCR products that contained two
      adjacent heterozygous loci using sequencing with specific primers, allele
      specific primers, and ddNTP-blocked primers. To validate its feasibility, two
      sets of PCR products, including two adjacent heterozygous SNPs, UGT1A1*6
      (rs4148323) and UGT1A1*28 (rs8175347), and two adjacent heterozygous SNPs, K1637K
      (rs11176013) and S1647T (rs11564148), were analyzed. Haplotypes of PCR products,
      including UGT1A1*6 and UGT1A1*28, were successfully analyzed by Sanger sequencing
      with allele-specific primers. Also, haplotypes of PCR products, including K1637K
      and S1647T, could not be determined by Sanger sequencing with allele-specific
      primers but were successfully analyzed by pyrosequencing with ddNTP-blocked
      primers. As a result, this method is able to effectively haplotype two adjacent
      heterozygous PCR products. It is simple, fast, and irrespective of short read
      length of pyrosequencing. Overall, we fully hope it will provide a new promising
      technology to identify haplotypes of conventional PCR products in clinical
      samples.

PMID- 29376066
TI  - What Each Clinical Anatomist Has to Know about Left Renal Vein Entrapment
      Syndrome (Nutcracker Syndrome): A Review of the Most Important Findings.
AB  - Nutcracker syndrome (NCS) is the most common term for compression of the left
      renal vein between the superior mesenteric artery and the abdominal aorta. The
      development of NCS is associated with the formation of the left renal vein (LRV)
      from the aortic collar during the sixth to eighth week of gestation and abnormal
      angulation of the superior mesenteric artery from the aorta. Collateralization of
      venous circulation is the most significant effect of NCS. It includes mainly the
      left gonadal vein and the communicating lumbar vein. Undiagnosed NCS may affect
      retroperitoneal surgery and other radiological and vascular procedures. The
      clinical symptoms of NCS may generally be described as renal presentation when
      symptoms like haematuria, left flank pain, and proteinuria occur, but urologic
      presentation is also possible. Radiological methods of confirming NCS include
      Doppler ultrasonography as a primary test, retrograde venography, which can
      measure the renocaval pressure gradient, computed tomography angiography, which
      is faster and less traumatic, intravascular ultrasound, and magnetic resonance
      angiography. Treatment can be conservative or surgical, depending on the severity
      of symptoms and degree of LRV occlusion. Nutcracker syndrome is worth considering
      especially in differential diagnosis of haematuria of unknown origin.

PMID- 29376068
TI  - A Meta-Analysis about the Screening Role of Pulse Oximetry for Congenital Heart
      Disease.
AB  - Objective: The opinions about the application of pulse oximetry in diagnosis of
      congenital heart disease (CHD) were debatable. We performed this meta-analysis to
      confirm the diagnostic role of pulse oximetry screening for CHD. Methods:
      Relevant articles were searched in the databases of Pubmed, Embase, Google
      Scholar, and Chinese National Knowledge Infrastructure (CNKI) up to April 2017.
      Data was processed in the MetaDiSc 1.4 software. Pooled sensitivity and
      specificity with 95% confidence interval (95% CI) were calculated to explain the
      diagnostic role of pulse oximetry screening for CHD. I2?50% or p < 0.05 indicated
      significant heterogeneity. Area under curve (AUC) of summary receiver operating
      characteristics (SROC) was calculated to assess its diagnostic accuracy. The
      robustness of overall results was evaluated by sensitivity analysis. Publication
      bias was evaluated by Deek's funnel plot. Results: 22 eligible articles were
      selected. Pooled sensitivity and specificity were 0.69 (0.67-0.72) and 0.99 (0.99
      0.99), respectively. The corresponding AUC was 0.9407, suggesting high diagnostic
      accuracy of pulse oximetry screening for CHD. Sensitivity analysis demonstrated
      that the pooled results were robust. Deek's funnel plot seemed to be symmetrical.
      Conclusions: Pulse oximetry screening could be used to diagnose CHD. It shows
      high diagnosis specificity and accuracy.

PMID- 29376067
TI  - Two-Stage Tissue-Expander Breast Reconstruction: A Focus on the Surgical
      Technique.
AB  - Objective: Breast cancer, the most common malignancy in women, comprises 18% of
      all female cancers. Mastectomy is an essential intervention to save lives, but it
      can destroy one's body image, causing both physical and psychological trauma.
      Reconstruction is an important step in restoring patient quality of life after
      the mutilating treatment. Material and Methods: Tissue expanders and implants are
      now commonly used in breast reconstruction. Autologous reconstruction allows a
      better aesthetic result; however, many patients prefer implant reconstruction due
      to the shorter operation time and lack of donor site morbidity. Moreover, this
      reconstruction strategy is safe and can be performed in patients with multiple
      health problems. Tissue-expander reconstruction is conventionally performed as a
      two-stage procedure starting immediately after mammary gland removal. Results:
      Mastectomy is a destructive but essential intervention for women with breast
      cancer. Tissue expansion breast reconstruction is a safe, reliable, and
      efficacious procedure with considerable psychological benefits since it provides
      a healthy body image. Conclusion: This article focuses on this surgical technique
      and how to achieve the best reconstruction possible.

PMID- 29376069
TI  - Ultrasound in Infertility Setting: Optimal Strategy to Evaluate the Assessment of
      Tubal Patency.
AB  - Tubal patency is a key element in women who are undergoing assisted reproductive
      techniques (ART), in order to attempt or exclude intrauterine insemination (IUI)
      cycles. Amongst the different procedures that can be used, without resorting to
      laparoscopy that remains the gold standard, hystero-salpingo-contrast sonography
      (HyCoSy) is an acceptable, time-efficient, and well tolerated option; it can be
      performed with administration of saline and air simultaneously or alternately
      (air/saline-HyCoSy), or with some other contrast agents, like SonoVue (sulfur
      hexafluoride microbubbles). In this paper, we describe two different studies: in
      the first one, our aim is to compare the efficiency of air/saline-HyCoSy with
      HyCoSy performed with contrast media (SonoVue), considering hysterosalpingography
      (HSG) and laparoscopy (LPS) as reference tests; in the second one, we estimate
      the pregnancy rate of a cohort of infertile women selected to undergo IUI cycles
      after tubal bilateral patency demonstration with air/saline-HyCoSy, to understand
      if this technique can be used as an efficient screening procedure in a
      Reproductive Unit.

PMID- 29376070
TI  - Increased Cardiovascular Risk in Patients with Adrenal Insufficiency: A Short
      Review.
AB  - Cardiovascular disease (CVD) is the most common cause of death in the world.
      Recent studies have shown an association between adrenal insufficiency (AI) and
      increased cardiovascular risk (CVR). Patients with AI receive glucocorticoid (GC)
      replacement therapy which can lead to varying levels of blood cortisol. It was
      shown that these imbalances in blood cortisol may lead to a higher prevalence of
      coronary heart disease, major adverse coronary events, and increased mortality.
      GC substitution is essential in the treatment of AI without which the disease has
      been shown to be fatal. The most frequently used GC formula for replacement
      therapy is hydrocortisone (HC). There is no uniform opinion on hydrocortisone
      replacement therapy. Alternative GC such as prednisolone is also in use.
      Overreplacement of GC may lead to adverse effects including obesity, high blood
      pressure, and hyperglycaemia. Outcome may vary between primary and secondary AI
      mainly due to differences in the renin-angiotensin-aldosterone system (RAAS).
      Furthermore, decreased blood levels of cortisol may lead to a compensatory
      secretion of inflammatory mediators such as Interleukin-1 (IL-1), Interleukin-6
      (IL-6), and/or tumor-necrosis factor (TNF). Physicians and patients should be
      properly educated about the increased risk of CVD in patients with AI.

PMID- 29376071
TI  - Mental Task Classification Scheme Utilizing Correlation Coefficient Extracted
      from Interchannel Intrinsic Mode Function.
AB  - In view of recent increase of brain computer interface (BCI) based applications,
      the importance of efficient classification of various mental tasks has increased
      prodigiously nowadays. In order to obtain effective classification, efficient
      feature extraction scheme is necessary, for which, in the proposed method, the
      interchannel relationship among electroencephalogram (EEG) data is utilized. It
      is expected that the correlation obtained from different combination of channels
      will be different for different mental tasks, which can be exploited to extract
      distinctive feature. The empirical mode decomposition (EMD) technique is employed
      on a test EEG signal obtained from a channel, which provides a number of
      intrinsic mode functions (IMFs), and correlation coefficient is extracted from
      interchannel IMF data. Simultaneously, different statistical features are also
      obtained from each IMF. Finally, the feature matrix is formed utilizing
      interchannel correlation features and intrachannel statistical features of the
      selected IMFs of EEG signal. Different kernels of the support vector machine
      (SVM) classifier are used to carry out the classification task. An EEG dataset
      containing ten different combinations of five different mental tasks is utilized
      to demonstrate the classification performance and a very high level of accuracy
      is achieved by the proposed scheme compared to existing methods.

PMID- 29376072
TI  - First-Line Helicobacter pylori Eradication in Patients with Chronic Kidney
      Diseases in Taiwan.
AB  - Aims: Patients with chronic kidney disease (CKD) and Helicobacter pylori (H.
      pylori) infection have a higher incidence of gastroduodenal diseases and
      therefore are recommended to receive eradication therapies. This study aimed to
      assess the efficacy of a 7-day standard triple therapy in patients with CKD (eGFR
      < 60 ml/min/1.73 m2) and to investigate the clinical factors influencing the
      success of eradication. Methods: A total of 758 patients with H. pylori infection
      receiving a 7-day standard first-line triple therapy between January 1, 2013, and
      December 31, 2014, were recruited. Patients were divided into two groups: CKD
      group (N = 130) and non-CKD group (N = 628). Results: The eradication rates
      attained by the CKD and non-CKD groups were 85.4% and 85.7%, respectively, in the
      per-protocol analysis (p = 0.933). The eradication rate in CKD stage 3 was 84.5%
      (82/97), in stage 4 was 88.2% (15/17), and in those who received hemodialysis was
      87.5% (14/16). There were no significant differences in the various stages of CKD
      (p = 0.982). The adverse events were similar between the two groups (3.1% versus
      4.6%, p = 0.433). Compliance between the two groups was good (100.0% versus
      99.8%, p = 0.649). There was no significant clinical factor influencing the H.
      pylori eradication rate in the non-CKD and CKD groups. Conclusions: This study
      suggests that the H. pylori eradication rate and adverse rate in patients with
      CKD are comparable to those of non-CKD patients.

PMID- 29376074
TI  - Catalytic Properties of Amylolytic Enzymes Produced by Gongronella butleri Using
      Agroindustrial Residues on Solid-State Fermentation.
AB  - Amylases catalyze the hydrolysis of starch, a vegetable polysaccharide abundant
      in nature. These enzymes can be utilized in the production of syrups, alcohol,
      detergent, pharmaceutical products, and animal feed formulations. The aim of this
      study was to optimize the production of amylases by the filamentous fungus
      Gongronella butleri by solid-state fermentation and to evaluate the catalytic
      properties of the obtained enzymatic extract. The highest amylase production,
      63.25 U g-1 (or 6.32 U mL-1), was obtained by culturing the fungus in wheat bran
      with 55% of initial moisture, cultivated for 96 h at 25 degrees C. The enzyme
      presented optimum activity at pH 5.0 and 55 degrees C. The amylase produced was
      stable in a wide pH range (3.5-9.5) and maintained its catalytic activity for 1 h
      at 40 degrees C. Furthermore, the enzymatic extract hydrolyzed starches from
      different vegetable sources, presenting predominant dextrinizing activity for all
      substrates evaluated. However, the presence of glucose was observed in a higher
      concentration during hydrolysis of corn starch, indicating the synergistic action
      of endo- and exoamylases, which enables the application of this enzymatic extract
      to produce syrups from different starch sources.

PMID- 29376075
TI  - Midterm Results of a New Rotating Hinge Knee Implant: A 5-Year Follow-Up.
AB  - Background: In the current study, we investigated midterm results of a new
      rotating hinge total knee arthroplasty (EnduRo prosthesis), which uses a new
      bearing material (CFR PEEK). Methods: We prospectively analysed data of 50
      patients with a minimum follow-up of 5 years. In 24 (48%) patients, a primary
      implantation was performed and 26 (52%) were revision cases. Clinical and
      radiographic examinations were performed preoperatively as well as
      postoperatively after 3 and 12 months and annually thereafter. The Knee Society
      Score (KSS), WOMAC, Oxford Knee Score (OKS), and range of motion (ROM) were used
      for clinical assessment. Results: KSS, WOMAC, OKS, and ROM significantly improved
      between the preoperative and the follow-up investigations. The overall survival
      rate with revision for any reason as an endpoint was 77.9% after five years. The
      number of complications was significantly higher in the revision group (p =
      0.003). Conclusion: The EnduRo prosthesis provides highly satisfying clinical and
      functional results in severe primary as well as in revision cases. Implant
      associated complications were rare. However, in cases of revision surgery, the
      risk for complications was considerably high, mostly related to previous joint
      infections and poor soft tissue quality.

PMID- 29376076
TI  - K Important Neighbors: A Novel Approach to Binary Classification in High
      Dimensional Data.
AB  - K nearest neighbors (KNN) are known as one of the simplest nonparametric
      classifiers but in high dimensional setting accuracy of KNN are affected by
      nuisance features. In this study, we proposed the K important neighbors (KIN) as
      a novel approach for binary classification in high dimensional problems. To avoid
      the curse of dimensionality, we implemented smoothly clipped absolute deviation
      (SCAD) logistic regression at the initial stage and considered the importance of
      each feature in construction of dissimilarity measure with imposing features
      contribution as a function of SCAD coefficients on Euclidean distance. The nature
      of this hybrid dissimilarity measure, which combines information of both features
      and distances, enjoys all good properties of SCAD penalized regression and KNN
      simultaneously. In comparison to KNN, simulation studies showed that KIN has a
      good performance in terms of both accuracy and dimension reduction. The proposed
      approach was found to be capable of eliminating nearly all of the noninformative
      features because of utilizing oracle property of SCAD penalized regression in the
      construction of dissimilarity measure. In very sparse settings, KIN also
      outperforms support vector machine (SVM) and random forest (RF) as the best
      classifiers.

PMID- 29376073
TI  - Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers.
AB  - Global reports estimate 600 million betel quid (BQ) chewers. BQ chewing has been
      demonstrated not only to be a risk factor for cancers of the oral cavity and
      pharynx and oral potentially malignant disorders (OPMD) but also to cause other
      cancers and adverse health effects. Herein, we summarized the international
      comparison data to aid in the understanding of the close relationship between the
      prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and
      adverse health effects. Potential biomarkers of BQ carcinogens, such as areca
      nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN), are closely
      associated with human health toxicology. Molecular mechanisms or pathways
      involving autophagy, hypoxia, COX-2, NF-kappaB activity, and stemness are known
      to be induced by BQ ingredients and are very closely related to the
      carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase
      (MAO) gene was associated with the occurrence and progress of oral and pharyngeal
      cancers. In summary, our review article provides important insights into the
      potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine
      products MNPN) and genetic factors (MAO) and offers a basis for studies aiming to
      reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the
      future.

PMID- 29376077
TI  - An Anatomical Study of Maxillary-Zygomatic Complex Using Three-Dimensional
      Computerized Tomography-Based Zygomatic Implantation.
AB  - Objective: To obtain anatomical data of maxillary-zygomatic complex based on
      simulating the zygomatic implantation using cadaver heads and three-dimensional
      computerized tomography (3D-CT). Methods: Simulating zygomatic implantation was
      performed using seven cadaver heads and 3D-CT images from forty-eight adults.
      After measuring the maxillary-zygomatic complex, we analyzed the position between
      the implantation path and the maxillary sinus cavity as well as the distance
      between the implantation path and the zygomatic nerve. Results: The distance from
      the starting point to the endpoint of the implant was 56.85 +/- 5.35 mm in
      cadaver heads and 58.15 +/- 7.37 mm in 3D-CT images. For the most common
      implantation path (80.20%), the implant went through the maxillary sinus cavity
      completely. The projecting points of the implant axis (IA) on the surface of
      zygoma were mainly located in the region of frontal process of zygomatic bone
      close to the lateral orbital wall. The distances between IA and zygomatic nerve
      in 53 sides were shorter than 2 mm. Conclusion: The simulating zygomatic
      implantation on cadaver skulls and 3D-CT imaging provided useful anatomical data
      of the maxillary-zygomatic complex. It is necessary to take care to avoid the
      zygomatic nerve injury during implantation, because it frequently appears on the
      route of implantation.

PMID- 29376078
TI  - Ameliorative Effect of Cactus (Opuntia ficus indica) Extract on Lithium-Induced
      Nephrocardiotoxicity: A Biochemical and Histopathological Study.
AB  - Opuntia ficus indica (family Cactaceae) is used in the treatment of a variety of
      conditions including metal-induced toxicity. The study reports the protective
      effects of Opuntia ficus indica (CCE) against lithium carbonate-induced toxicity
      in rats. Nephrocardiotoxicity was induced in male Wistar rats by single dose of
      lithium carbonate (25 mg/kg b.w twice daily for 30 days). Aqueous extract of
      Opuntia ficus indica was administered at the dose of 100 mg/kg of b.w by gavage
      for 60 days. Obtained results revealed that administration of lithium carbonate
      caused a significant increase in serum creatinine, uric acid, and urea levels.
      Additionally, a significant decrease in the level of renal and cardiac SOD, CAT,
      and GPx activities was associated with a significant increase of MDA levels in
      lithium carbonate group more than those of the control. However, the treatment of
      experimental rats with CCE prevented these alterations and maintained the
      antioxidant status. The histopathological observations supported the biochemical
      evidences of nephrocardioprotection. CCE supplementation could protect against
      lithium carbonate-induced renal and cardiac injuries in rats, plausibly by the
      upregulation of antioxidant enzymes and inhibition of MDA to confer the
      protective effect.

PMID- 29376079
TI  - Triclocarban and Triclosan Inhibit Human Aromatase via Different Mechanisms.
AB  - Human aromatase (CYP19A1) is an important enzyme, which produces estrogen from
      androgen for maintaining the female reproductive function and pregnancy.
      Triclocarban and triclosan are antimicrobial chemicals added to personal care,
      household, and industrial products. They could be endocrine disruptors and may
      disrupt human CYP19A1 activity. In the present study, we investigated the effects
      of triclocarban and triclosan on estradiol production and human CYP19A1 activity
      in JEG-3 cells. Triclocarban and triclosan reduced estradiol production in JEG-3
      cells. Triclocarban and triclosan inhibited human CYP19A1 with IC50 values of
      15.81 and 6.26 MUM, respectively. Triclosan competitively inhibited CYP19A1,
      while triclocarban noncompetitively inhibited this enzyme. Docking study showed
      that triclosan bound to the steroid-binding pocket of CYP19A1, while triclocarban
      was off this target, suggesting a different mechanism. In conclusion,
      triclocarban and triclosan are inhibitors of human CYP19A1.

PMID- 29376080
TI  - Parental Diabetes Behaviors and Distress Are Related to Glycemic Control in Youth
      with Type 1 Diabetes: Longitudinal Data from the DINO Study.
AB  - Objective: To evaluate (1) the longitudinal relationship between parental well
      being and glycemic control in youth with type 1 diabetes and (2) if youth's
      problem behavior, diabetes parenting behavior, and parental diabetes-distress
      influence this relationship. Research Design and Methods: Parents of youth 8-15
      yrs (at baseline) (N = 174) participating in the DINO study completed
      questionnaires at three time waves (1 yr interval). Using generalized estimating
      equations, the relationship between parental well-being (WHO-5) and youth's HbA1c
      was examined. Second, relationships between WHO-5, Strength and Difficulties
      Questionnaire (SDQ), Diabetes Family Behavior Checklist (DFBC), Problem Areas In
      Diabetes-Parent Revised (PAID-Pr) scores, and HbA1c were analyzed. Results: Low
      well-being was reported by 32% of parents. No relationship was found between
      parents' WHO-5 scores and youth's HbA1c (beta = -0.052, p = 0.650). WHO-5 related
      to SDQ (beta = -0.219, p < 0.01), DFBC unsupportive scale (beta = -0.174, p <
      0.01), and PAID-Pr (beta = -0.666, p < 0.01). Both DFBC scales (supportive beta =
      -0.259, p = 0.01; unsupportive beta = 0.383, p = 0.017), PAID-Pr (beta = 0.276, p
      < 0.01), and SDQ (beta = 0.424, p < 0.01) related to HbA1c. Conclusions: Over
      time, reduced parental well-being relates to increased problem behavior in youth,
      unsupportive parenting, and parental distress, which negatively associate with
      HbA1c. More unsupportive diabetes parenting and distress relate to youth's
      problem behavior.

PMID- 29376082
TI  - Corrigendum to "Gene Expression Profiles of Human Phosphotyrosine Phosphatases
      Consequent to Th1 Polarisation and Effector Function".
AB  - [This corrects the article DOI: 10.1155/2017/8701042.].

PMID- 29376081
TI  - A Comprehensive Review of US FDA-Approved Immune Checkpoint Inhibitors in
      Urothelial Carcinoma.
AB  - Few effective treatment options are available for patients with advanced or
      metastatic urothelial carcinoma (UC) after unsuccessful first-line platinum-based
      chemotherapy. To date, immune checkpoint inhibitors are novel therapeutic agents
      for UC treatment. From May 2016 to May 2017, five anti-PD-1/PD-L1 monoclonal
      antibodies received accelerated or regular approval from the US Food and Drug
      Administration (FDA) for the treatment of patients with locally advanced or
      metastatic UC. The present comprehensive review presents the background
      information of these five US FDA-approved anticancer agents to provide a basic
      but concise understanding of these agents for advanced studies. We summarize
      their immune checkpoint mechanisms, clinical efficacy, recommended usage
      protocols, adverse events, and the limitations of the PD-L1 biomarker assays.

PMID- 29376083
TI  - Evaluating Variance Estimators for Respondent-Driven Sampling.

PMID- 29376084
TI  - Chinese Ethnicity Is Associated With Concomitant Cartilage Injuries in Anterior
      Cruciate Ligament Tears.
AB  - Background: Chinese ethnicity is associated with the presence of knee
      osteoarthritis. This raises the possibility that it may similarly be associated
      with concomitant meniscus and cartilage injuries in patients with anterior
      cruciate ligament (ACL) tears. There are currently no published data on the
      effect of Chinese ethnicity in this regard. Purpose: The primary aim was to
      determine whether Chinese ethnicity is associated with concomitant intra
      articular injuries in patients with ACL tears and to verify the correlation of
      age, sex, body mass index, mechanism of injury, cause of injury, and presence of
      bone contusions on magnetic resonance imaging with such injuries. A secondary
      purpose was to determine the optimal time frame for surgical reconstruction in
      patients with identified risk factors for concomitant injuries. Study Design:
      Cohort study; Level of evidence, 3. Methods: The medical records of 696 patients
      from a multiethnic population who underwent ACL reconstruction from January 2013
      to August 2016 were retrospectively analyzed. Univariate and multivariate
      logistic regression analyses were performed to identify patient factors that were
      associated with medial meniscus tears, lateral meniscus tears, and cartilage
      injuries. Further univariate analysis was conducted to determine the earliest
      time point for surgery, after which the rate of concomitant injuries was
      significantly higher. Results: Over half (69.1%, n = 481) of our study population
      sustained at least 1 other concomitant knee injury. Meniscus tears were most
      frequently associated with ACL tears (24.1% medial, 25.6% lateral, and 15.5%
      medial and lateral meniscus tears). Cartilage injuries were present in 18.4% of
      our cohort. Chinese ethnicity was associated with concomitant cartilage injuries.
      Increased age (>=30 years) was significantly associated with cartilage injuries
      and male sex with medial and lateral meniscus tears. Among patients with these
      factors, significantly fewer medial meniscus tears and cartilage injuries were
      noted when surgery was carried out within 12 months of the index trauma.
      Conclusion: This is one of the first studies to have identified an association
      between Chinese ethnicity and concomitant cartilage injuries in ACL tears. This
      study also found an association between increased age and an increased prevalence
      of cartilage injuries. Male sex was associated with both medial and lateral
      meniscus tears. Definitive surgery should be performed within 12 months of the
      index injury to minimize further intra-articular injuries.

PMID- 29376085
TI  - Anterolateral Ligament Reconstruction: A Possible Option in the Therapeutic
      Arsenal for Persistent Rotatory Instability After ACL Reconstruction.

PMID- 29376086
TI  - Sport Specialization Characteristics Between Rural and Suburban High School
      Athletes.
AB  - Background: Sport specialization has been associated with overuse injuries and is
      more common in larger high schools, which are often located in more
      urban/suburban settings. However, sport participation characteristics have not
      been compared between suburban and rural high schools. Purpose/Hypothesis: The
      purpose of this study was to examine the differences in sport participation
      characteristics between athletes at suburban and rural high schools. It was
      hypothesized that suburban high school students would be more likely to be highly
      specialized, participate in more athletic competitions per year, and play in a
      league outside of school. We also hypothesized that suburban high school students
      would start playing their primary sport at a younger age, would have participated
      in their primary sport for longer, and would play more months per year and hours
      per week. Study Design: Cross-sectional study. Methods: High school athletes from
      4 high schools (2 suburban and 2 rural) participated in this study (N = 354 [222
      females]; mean age, 15.7 +/- 1.2 years). Athletes were on a school-sponsored
      athletic team in 1 of 4 sports (volleyball, tennis, basketball, soccer). The
      suburban schools (study enrollment, n = 226) had total school enrollments of 2271
      and 622 students, while the rural schools (study enrollment, n = 128) had total
      school enrollments of 443 and 297. Participants completed a questionnaire prior
      to the start of their high school sport season. The questionnaire consisted of
      demographic information, a sport specialization scale, and sport participation
      information. Primary sport competition volume in the previous 12 months was
      classified as high (>60 primary sport competitions), moderate (30-60), or low
      (<30). Sport specialization status was classified via a 3-point scale as low,
      moderate, or high. Results: As compared with athletes at rural schools, athletes
      at suburban schools started playing their primary sport at a younger age
      (suburban, 7.8 +/- 2.9 years; rural, 9.7 +/- 3.2 years; P < .001) and
      participated for more years (suburban, 7.9 +/- 3.1 years; rural, 6.1 +/- 3.3
      years; P < .001), more months per year (suburban, 7.6 +/- 3.6 months; rural, 5.6
      +/- 2.8 months; P < .001), and more hours per week (suburban, 15.2 +/- 5.1 hours;
      rural, 12.9 +/- 3.3 hours; P < .001). Athletes at suburban schools were more
      likely than rural athletes to be classified as highly specialized (chi2 = 52.5, P
      < .001), participate in more competitions (chi2 = 16.5, P < .001), play in a
      league outside of school (chi2 = 18.4, P < .001), and train in their primary
      sport for >8 months per year (chi2 = 27.8, P < .001) and >16 hours per week (chi2
      = 15.0, P < .001). Conclusion: High school athletes at suburban schools are more
      likely to exhibit sport participation patterns that are associated with increased
      risk of overuse injury. These include being classified as highly specialized,
      playing their primary sport >8 months per year and >16 hours per week, engaging
      in a high competition volume, and participating in a sport league (eg, club)
      outside of school. Efforts aimed at safe sport participation should target these
      groups, as they seem more likely to violate safe sport recommendations.

PMID- 29376087
TI  - Diagnostic Potential of Neural Exosome Cargo as Biomarkers for Acute Brain
      Injury.
AB  - Objective: Neuronal exosomes purified from peripheral blood samples have been
      proposed as diagnostic tool in the setting of acute brain injury but never tested
      clinically. We hypothesized that exosome protein biomarkers would change over
      time following acute hypoxic brain injury and would predict response to therapy.
      Methods: Synaptopodin (SYNPO), an actin-associated protein present in
      postsynaptic spines, was evaluated as a potential biomarker as well as:
      synaptophysin, neuron-specific enolase, and mitochondrial cytochrome c oxidase. A
      secondary analysis was performed on neonatal samples collected at 8, 10, and 14 h
      after the initiation of therapeutic-controlled hypothermia for acute hypoxic
      ischemic encephalopathy (n = 14). Neuronal exosomes were purified from serum and
      protein levels were quantified using standard ELISA methods. The primary study
      outcomes were length of stay (LOS), discharge on seizure medication (DCMED), and
      composite neuroimaging score (NIS). Results: The slope of change in neuronal
      exosome SYNPO between 8 and 14 h appeared to be the most promising biomarker for
      all three clinical study outcomes. SYNPO was highly correlated with LOS (-0.91, P
      < 0.001). SYNPO increased in 6/8 without DCMED and was worse or neutral in 5/5
      with DCMED (P = 0.02). All four neonates with an abnormal NIS had neutral or
      decreasing SYNPO (P = 0.055). Other candidate biomarkers were not associated with
      outcomes. Interpretation: This report provides the first clinical evidence that
      neural exosomes turn over rapidly enough in the peripheral circulation to be used
      as a "troponin-like" test following acute brain injury. Optimal sampling and
      biomarkers likely vary with type of brain injury.

PMID- 29376088
TI  - An in vivo 11C-PK PET study of microglia activation in Fatal Familial Insomnia.
AB  - Objective: Postmortem studies reported significant microglia activation in
      association with neuronal apoptosis in Fatal Familial Insomnia (FFI), indicating
      a specific glial response, but negative evidence also exists. An in vivo study of
      local immune responses over FFI natural course may contribute to the
      understanding of the underlying pathogenesis. Methods: We included eight
      presymptomatic subjects (mean +/- SD age:44.13 +/- 3.83 years) carrying the
      pathogenic D178N-129met FFI mutation, one symptomatic patient (male, 45 yrs.
      old), and nine healthy controls (HC) (mean +/- SD age: 44.00 +/- 11.10 years.)
      for comparisons. 11C-(R)-PK11195 PET allowed the measurement of Translocator
      Protein (TSPO) overexpression, indexing microglia activation. A clustering
      algorithm was adopted to define subject-specific reference regions. Voxel-wise
      statistical analyses were performed on 11C-(R)-PK11195 binding potential (BP)
      images both at the group and individual level. Results: The D178N-129met/val FFI
      patient showed significant 11C-(R)-PK11195 BP increases in the midbrain,
      cerebellum, anterior thalamus, anterior cingulate cortex, orbitofrontal cortex,
      and anterior insula, bilaterally. Similar TSPO increases, but limited to limbic
      structures, were observed in four out of eight presymptomatic carriers. The only
      carrier with the codon 129met/val polymorphism was the only one showing an
      additional TSPO increase in the anterior thalamus. Interpretation: In comparison
      to nonprion neurodegenerative diseases, the observed lack of a diffuse brain TSPO
      overexpression in preclinical and the clinical FFI cases suggests the presence of
      a different microglia response. The involvement of limbic structures might
      indicate a role for microglia activation in these key pathologic regions, known
      to show the most significant neuronal loss and functional deafferentation in FFI.

PMID- 29376089
TI  - MRI biomarkers of proximal nerve injury in CIDP.
AB  - Objective: To evaluate the utility of nerve diffusion tensor imaging (DTI), nerve
      cross-sectional area, and muscle magnetic resonance imaging (MRI) multiecho Dixon
      for assessing proximal nerve injury in chronic inflammatory demyelinating
      polyneuropathy (CIDP). Methods: In this prospective observational cohort study,
      11 patients with CIDP and 11 healthy controls underwent a multiparametric MRI
      protocol with DTI of the sciatic nerve and assessment of muscle proton-density
      fat fraction of the biceps femoris and the quadriceps femoris muscles by
      multiecho Dixon MRI. Patients were longitudinally evaluated by MRI, clinical
      examination, and nerve conduction studies at baseline and after 6 months.
      Results: In sciatic nerves of CIDP patients, mean cross-sectional area was
      significantly higher and fractional anisotropy value was significantly lower,
      compared to controls. In contrast, muscle proton-density fat fraction was
      significantly higher in thigh muscles of patients with CIDP, compared to
      controls. MRI parameters showed high reproducibility at baseline and 6 months.
      Interpretation: Advanced MRI parameters demonstrate subclinical proximal nerve
      damage and intramuscular fat accumulation in CIDP. Data suggest DTI and multiecho
      Dixon MRI might be useful in estimating axonal damage and neurogenic muscle
      changes in CIDP.

PMID- 29376090
TI  - Cognitive impairment in epilepsy: the role of reduced network flexibility.
AB  - Objective: The dominant model of cognitive impairment in focal epilepsy has
      emphasised structural bases for cognitive deficits. Current theories of cognition
      in the healthy brain emphasise the importance of the reweighting of brain network
      interactions in support of task performance. Here, we explore the hypothesis that
      cognitive deficits in epilepsy arise through abnormalities of dynamic functional
      network interactions. Method: We studied 19 healthy controls and 37 temporal lobe
      epilepsy (TLE) patients, using a behavioural measure of verbal fluency (the
      Controlled Oral Word Association Test) and an fMRI verbal fluency paradigm
      (Orthographic Lexical Retrieval). Results: Behaviourally, verbal fluency was
      significantly impaired in TLE. Psychophysiological interaction analyses of the
      fMRI data, which capture state-dependent changes in network connectivity,
      revealed reduced task-dependent modulations of connectivity from left superior
      medial frontal cortex to left middle frontal gyrus in TLE patients. Individual
      differences in verbal fluency among TLE cases was correlated with task-dependent
      changes in connectivity from left posterior cingulate to left superior medial
      frontal cortex, and from left superior medial frontal cortex to a range of right
      predominant brain areas. Interpretation: These data reveal that the typical
      pattern of task-driven shifts in network connectivity is not observed in TLE. Our
      observations go beyond simple structure-function associations and suggest that
      failure of network flexibility can be an important contributor to cognitive
      impairment in epilepsy.

PMID- 29376091
TI  - ABCA7 and risk of dementia and vascular disease in the Danish population.
AB  - Objective: ATP-binding-cassette transporter A7(ABCA7) is suggested to be involved
      in lipid transport as well as in phagocytosis of amyloid-beta in the brain. We
      tested the hypothesis that a common genetic variant in ABCA7 is associated with
      dementia, ischemic heart disease, ischemic cerebrovascular disease, and with
      lipid levels in the general population, independent of the common apolipoprotein
      E(APOE) genotype. Methods: For this purpose, we genotyped a common genetic
      variant in ABCA7, identified in genome-wide-association-studies of Alzheimer's
      disease, in 104,258 individuals from the Danish general population, and also meta
      analyzed our results with publicly available consortia data. Results:
      Multifactorially adjusted hazard ratios for Alzheimer's disease were 1.07 (95%
      confidence interval:0.93-1.23) and 1.72 (1.24-2.40) for GA and AA versus GG
      genotype. Results were similar after APOE genotype adjustment and when only APOE
      E33 carriers were studied. Including 178,304 individuals, the meta-analyzed odds
      ratio for Alzheimer's disease per one allele ABCA7 rs4147929 increase was 1.15
      (1.12-1.18). ABCA7 genotype was not convincingly associated with vascular
      dementia, ischemic heart disease, ischemic cerebrovascular disease, or with lipid
      levels. Including 288,563 individuals, meta-analyzed odds ratios for ischemic
      heart disease per one allele ABCA7 rs4147929 increase was 1.01 (0.99-1.03).
      Interpretation: A common genetic variant in ABCA7 was associated with high risk
      of Alzheimer's disease independent of APOE genotype. The lack of association with
      vascular dementia, ischemic heart disease, ischemic cerebrovascular disease, and
      with lipid levels suggests that ABCA7 is not important for atherosclerosis. Thus,
      our findings support the suggested role of ABCA7 in Alzheimer's disease pathology
      and phagocytic clearance of amyloid-beta in the brain.

PMID- 29376092
TI  - Neuronal activity and outcomes from thalamic surgery for spinocerebellar ataxia.
AB  - Objectives: We investigated the effects of deep brain stimulation (DBS) or
      lesions of the ventral intermediate nucleus (Vim) of the thalamus for
      spinocerebellar ataxia (SCA) and examined the pathophysiological role of neuronal
      activity of the Vim underlying ataxia. Methods: Five patients with SCA with
      cortical atrophy (ages 60-69 years; 2 sporadic and three familial SCA) and five
      patients with essential tremor (ET) (ages 57-71 years) were treated with Vim
      surgery. Intraoperatively, we recorded neuronal activity from single neurons in
      the Vim thalamus while patients were at rest and compared the physiological
      properties of those neurons between patients with SCA and those with ET. Results:
      Postsurgery mean scores for the Fahn-Tolosa-Marin Tremor Scale were improved from
      78 to 44 in SCA patients and from 54 to 21 in ET patients. Stronger stimulation
      was necessary to optimize outcomes in SCA as compared to ET patients. We analyzed
      68 Vim neurons in SCA and 60 Vim neurons in ET. Mean discharge rates, burst
      characteristics, and oscillatory activity were similar for both patient groups,
      however, we observed that the ratio of cells responding to passive manipulation
      was significantly smaller (P = 0.0001) in SCA (22%) than in ET (71%).
      Interpretation: Thalamic surgery led to a significant improvement in tremor in
      SCA patients. One potential mechanism underlying ataxia in SCA may be disruption
      of cerebellar sensory feedback, which modulates motor commands in the cerebello
      thalamo-cortical network.

PMID- 29376093
TI  - Lifelong behavioral and neuropathological consequences of repetitive mild
      traumatic brain injury.
AB  - Objective: Exposure to repetitive concussion, or mild traumatic brain injury
      (mTBI), has been linked with increased risk of long-term neurodegenerative
      changes, specifically chronic traumatic encephalopathy (CTE). To date,
      preclinical studies largely have focused on the immediate aftermath of mTBI, with
      no literature on the lifelong consequences of mTBI in these models. This study
      provides the first account of lifelong neurobehavioral and histological
      consequences of repetitive mTBI providing unique insight into the constellation
      of evolving and ongoing pathologies with late survival. Methods: Male C57BL/6J
      mice (aged 2-3 months) were exposed to either single or repetitive mild TBI or
      sham procedure. Thereafter, animals were monitored and assessed at 24 months post
      last injury for measures of motor coordination, learning deficits, cognitive
      function, and anxiety-like behavior prior to euthanasia and preparation of the
      brains for detailed neuropathological and protein biochemical studies. Results:
      At 24 months survival animals exposed to r-mTBI showed clear evidence of learning
      and working memory impairment with a lack of spatial memory and vestibule-motor
      vestibulomotor deficits compared to sham animals. Associated with these late
      behavioral deficits there was evidence of ongoing axonal degeneration and
      neuroinflammation in subcortical white matter tracts. Notably, these changes were
      also observed after a single mTBI, albeit to a lesser degree than repetitive
      mTBI. Interpretation: In this context, our current data demonstrate, for the
      first time, that rather than an acute, time limited event, mild TBI can
      precipitate a lifelong degenerative process. These data therefore suggest that
      successful treatment strategies should consider both the acute and chronic nature
      of mTBI.

PMID- 29376094
TI  - Cognitive clinico-radiological paradox in early stages of multiple sclerosis.
AB  - Objective: To investigate whether the strength of the association between
      magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between
      various multiple sclerosis subpopulations. Methods: A total of 1052 patients were
      included in this large cross-sectional study. Brain MRI (T1 and T2 lesion volume
      and brain parenchymal fraction) and neuropsychological assessment (Brief
      International Cognitive Assessment for Multiple Sclerosis and Paced Auditory
      Serial Addition Test) were performed. Results: Weak correlations between
      cognitive domains and MRI measures were observed in younger patients (age<=30
      years; absolute Spearman's rho = 0.05-0.21), with short disease duration (<2
      years; rho = 0.01-0.21), low Expanded Disability Status Scale [EDSS] (<=1.5; rho
      = 0.08-0.18), low T2 lesion volume (lowest quartile; <0.59 mL; rho = 0.01-0.20),
      and high brain parenchymal fraction (highest quartile; >86.66; rho = 0.01-0.16).
      Stronger correlations between cognitive domains and MRI measures were observed in
      older patients (age>50 years; rho = 0.24-0.50), with longer disease duration (>15
      years; rho = 0.26-0.53), higher EDSS (>=5.0; rho = 0.23-0.39), greater T2 lesion
      volume (highest quartile; >5.33 mL; rho = 0.16-0.32), and lower brain parenchymal
      fraction (lowest quartile; <83.71; rho = 0.13-0.46). The majority of these
      observed results were confirmed by significant interactions (P <= 0.01) using
      continuous variables. Interpretation: The association between structural brain
      damage and functional cognitive impairment is substantially weaker in multiple
      sclerosis patients with a low disease burden. Therefore, disease stage should be
      taken into consideration when interpreting associations between structural and
      cognitive measures in clinical trials, research studies, and clinical practice.

PMID- 29376095
TI  - Massive cortical reorganization is reversible following bilateral transplants of
      the hands: evidence from the first successful bilateral pediatric hand transplant
      patient.
AB  - In this repeated measures case study, we show that sensory deafferentation after
      limb amputation leads to changes in cortical somatotopic maps which are
      reversible after restoration of sensory input. Using magnetoencephalography
      (MEG), we observed in a child with bilateral hand transplants large-scale shifts
      in somatosensory lip cortical representation from anatomic hand area to anatomic
      face region. After recovery of tactile sensation in the digits, responses to
      finger stimulation were localized to orthotopic sensory cortex, but with atypical
      electrophysiologic features (amplitude and frequencies).

PMID- 29376096
TI  - Birth and death of a phantom.
AB  - Patients with supernumerary phantom limb report experiencing an additional limb
      duplicating its physical counterpart, usually following a stroke with
      sensorimotor disturbances. Here, we report a short-lasting case of a right upper
      supernumerary phantom limb with unusual visuomotor features in a healthy
      participant during a pure Jacksonian motor seizure unexpectedly induced by
      continuous Theta-Burst Stimulation over the left primary motor cortex.
      Electromyographic correlates of the event followed the phenomenological pattern
      of sudden appearance and brutal dissolution of the phantom, adding credit to the
      hypothesis that supernumerary phantom limb results from a dynamic resolution of
      conflictual multimodal information.

PMID- 29376097
TI  - Xeroderma pigmentosum is a definite cause of Huntington's disease-like syndrome.
AB  - Xeroderma pigmentosum is characterized by cutaneous, ophthalmological, and
      neurological features. Although it is typical of childhood, late presentations
      can mimic different neurodegenerative conditions. We report two families
      presenting as Huntington's disease-like syndromes. The first case (group G)
      presented with neuropsychiatric features, cognitive decline and chorea. Typical
      lentigines were only noticed after the neurological disease started. The second
      case (group B) presented adult-onset chorea and neuropsychiatric symptoms after
      an aggressive ocular melanoma. Xeroderma pigmentosum can manifest as a
      Huntington's Disease-like syndrome. Classic dermatological and oncological
      features have to be investigated in choreic patients with negative genetic tests
      for Huntington's disease-like phenotypes.

PMID- 29376098
TI  - Combining clinical and biofluid markers for early Parkinson's disease detection.
AB  - Accurate early diagnosis of Parkinson's disease is essential. Using data
      available from the Parkinson's Progression Markers Initiative study, we
      identified a multivariate logistic regression model including cerebrospinal fluid
      alpha-synuclein, olfactory function, age, and gender that achieved a high degree
      of discrimination between patients with Parkinson's disease and healthy control
      or scan without evidence of dopaminergic deficit participants. Additionally, the
      model could predict the conversion of scan without evidence of dopaminergic
      deficit to Parkinson's disease, as well as discriminate between normal and
      impaired subjects with leucine-rich repeat kinase 2 mutations. Although further
      validation is needed, this model may serve as an alternative method to
      neuroimaging screening in Parkinson's disease studies.

PMID- 29376100
TI  - Are ventrolateral and dorsolateral prefrontal cortices involved in the
      computerized Corsi block-tapping test execution? An fNIRS study.
AB  - The Corsi block-tapping test (CBT) is an old neuropsychological test that,
      requiring the storage and the reproduction of spatial locations, assesses spatial
      working memory (WM). Despite its wide use in clinical practice, the specific
      contribution of prefrontal cortex (PFC) subregions during CBT execution has not
      been clarified yet. Considering the importance of spatial WM in daily life and
      the well-known role of ventrolateral-PFC/dorsolateral-PFC (VLPFC/DLPFC) in WM
      processes, the present study was aimed at investigating, by a 20-channel
      functional near-infrared spectroscopy (fNIRS) system (including four short
      separation channels), the hemodynamic response of the VLPFC/DLPFC during a
      computerized version of the CBT. Thirty-nine university students were asked to
      perform CBT standard version (CBTs), block-suppression CBT (CBTb), and control
      task (CBTc). A VLPFC activation during CBTs and a DLPFC activation during CBTb
      were hypothesized. The results of the Bayesian analysis have not shown a
      delineated specific activation of VLPFC/DLPFC during either CBTs or CBTb. These
      results together with the related ones obtained by others using fMRI are not
      sufficient to definitively state the role of the PFC subregions during CBT
      execution. The adoption of high-density diffuse optical tomography would be
      helpful in further exploration of the PFC involvement in spatial WM tasks.

PMID- 29376102
TI  - Quantification of uncertainty in the assessment of coronary plaque in CCTA
      through a dynamic cardiac phantom and 3D-printed plaque model.
AB  - The purpose of this study was to develop a dynamic physical cardiac phantom with
      a realistic coronary plaque to investigate stenosis measurement accuracy under
      clinically relevant heart-rates. The coronary plaque model (5 mm diameter, 50%
      stenosis, and 32 mm long) was designed and 3D-printed with tissue equivalent
      materials (calcified plaque with iodine-enhanced lumen). Realistic cardiac motion
      was modeled by converting computational cardiac motion vectors into compression
      and rotation profiles executed by a commercial base cardiac phantom. The phantom
      was imaged on a dual-source CT system applying a retrospective gated coronary CT
      angiography (CCTA) protocol using synthesized motion-synchronized
      electrocardiogram (ECG) waveforms. Multiplanar reformatted images were
      reconstructed along vessel centerlines. Enhanced lumens were segmented by five
      independent operators. On average, stenosis measurement accuracy was 0.9%
      positively biased for the motion-free condition. Average measurement accuracy
      monotonically decreased from 0.9% positive bias for the motion-free condition to
      18.5% negative bias at 90 beats per minute. Contrast-to-noise ratio, lumen
      circularity, and segmentation conformity also decreased monotonically with
      increasing heart-rate. These results demonstrate successful implementation of a
      base cardiac phantom with a 3D-printed coronary plaque model, relevant motion
      profile, and coordinated ECG waveform. They further show the utility of the model
      to ascertain metrics of CCTA accuracy and image quality under realistic plaque,
      motion, and acquisition conditions.

PMID- 29376104
TI  - Pairwise domain adaptation module for CNN-based 2-D/3-D registration.
AB  - Accurate two-dimensional to three-dimensional (2-D/3-D) registration of
      preoperative 3-D data and intraoperative 2-D x-ray images is a key enabler for
      image-guided therapy. Recent advances in 2-D/3-D registration formulate the
      problem as a learning-based approach and exploit the modeling power of
      convolutional neural networks (CNN) to significantly improve the accuracy and
      efficiency of 2-D/3-D registration. However, for surgery-related applications,
      collecting a large clinical dataset with accurate annotations for training can be
      very challenging or impractical. Therefore, deep learning-based 2-D/3-D
      registration methods are often trained with synthetically generated data, and a
      performance gap is often observed when testing the trained model on clinical
      data. We propose a pairwise domain adaptation (PDA) module to adapt the model
      trained on source domain (i.e., synthetic data) to target domain (i.e., clinical
      data) by learning domain invariant features with only a few paired real and
      synthetic data. The PDA module is designed to be flexible for different deep
      learning-based 2-D/3-D registration frameworks, and it can be plugged into any
      pretrained CNN model such as a simple Batch-Norm layer. The proposed PDA module
      has been quantitatively evaluated on two clinical applications using different
      frameworks of deep networks, demonstrating its significant advantages of
      generalizability and flexibility for 2-D/3-D medical image registration when a
      small number of paired real-synthetic data can be obtained.

PMID- 29376103
TI  - Virtual assessment of stereoscopic viewing of digital breast tomosynthesis
      projection images.
AB  - Digital breast tomosynthesis (DBT) acquires a series of projection images from
      different angles as an x-ray source rotates around the breast. Such imaging
      geometry lends DBT naturally to stereoscopic viewing as two projection images
      with a reasonable separation angle can easily form a stereo pair. This simulation
      study assessed the efficacy of stereo viewing of DBT projection images. Three
      dimensional computational breast phantoms with realistically shaped synthetic
      lesions were scanned by three simulated DBT systems. The projection images were
      combined into a sequence of stereo pairs and presented to a stereomatching-based
      model observer for deciding lesion presence. Signal-to-noise ratio was estimated,
      and the detection performance with stack viewing of reconstructed slices was the
      benchmark. We have shown that: (1) stereo viewing of projection images may
      underperform stack viewing of reconstructed slices for current DBT geometries;
      (2) DBT geometries may impact the efficacy of the two viewing modes differently:
      narrow-arc and wide-arc geometries may be better for stereo viewing and stack
      viewing, respectively; (3) the efficacy of stereo viewing may be more robust than
      stack viewing to reductions in dose. While in principle stereo viewing is
      potentially effective for visualizing DBT data, effective stereo viewing may
      require specifically optimized DBT image acquisition.

PMID- 29376105
TI  - PSNet: prostate segmentation on MRI based on a convolutional neural network.
AB  - Automatic segmentation of the prostate on magnetic resonance images (MRI) has
      many applications in prostate cancer diagnosis and therapy. We proposed a deep
      fully convolutional neural network (CNN) to segment the prostate automatically.
      Our deep CNN model is trained end-to-end in a single learning stage, which uses
      prostate MRI and the corresponding ground truths as inputs. The learned CNN model
      can be used to make an inference for pixel-wise segmentation. Experiments were
      performed on three data sets, which contain prostate MRI of 140 patients. The
      proposed CNN model of prostate segmentation (PSNet) obtained a mean Dice
      similarity coefficient of [Formula: see text] as compared to the manually labeled
      ground truth. Experimental results show that the proposed model could yield
      satisfactory segmentation of the prostate on MRI.

PMID- 29376106
TI  - Preface to Swiss National Center of Competence in Research: Molecular Ultrafast
      Science and Technology.

PMID- 29376107
TI  - Ultrafast dynamics induced by the interaction of molecules with electromagnetic
      fields: Several quantum, semiclassical, and classical approaches.
AB  - Several strategies for simulating the ultrafast dynamics of molecules induced by
      interactions with electromagnetic fields are presented. After a brief overview of
      the theory of molecule-field interaction, we present several representative
      examples of quantum, semiclassical, and classical approaches to describe the
      ultrafast molecular dynamics, including the multiconfiguration time-dependent
      Hartree method, Bohmian dynamics, local control theory, semiclassical thawed
      Gaussian approximation, phase averaging, dephasing representation, molecular
      mechanics with proton transfer, and multipolar force fields. In addition to the
      general overview, some focus is given to the description of nuclear quantum
      effects and to the direct dynamics, in which the ab initio energies and forces
      acting on the nuclei are evaluated on the fly. Several practical applications,
      performed within the framework of the Swiss National Center of Competence in
      Research "Molecular Ultrafast Science and Technology," are presented: These
      include Bohmian dynamics description of the collision of H with H2, local control
      theory applied to the photoinduced ultrafast intramolecular proton transfer,
      semiclassical evaluation of vibrationally resolved electronic absorption,
      emission, photoelectron, and time-resolved stimulated emission spectra, infrared
      spectroscopy of H-bonding systems, and multipolar force fields applications in
      the condensed phase.

PMID- 29376108
TI  - Nonadiabatic effects in electronic and nuclear dynamics.
AB  - Due to their very nature, ultrafast phenomena are often accompanied by the
      occurrence of nonadiabatic effects. From a theoretical perspective, the treatment
      of nonadiabatic processes makes it necessary to go beyond the (quasi) static
      picture provided by the time-independent Schrodinger equation within the Born
      Oppenheimer approximation and to find ways to tackle instead the full time
      dependent electronic and nuclear quantum problem. In this review, we give an
      overview of different nonadiabatic processes that manifest themselves in
      electronic and nuclear dynamics ranging from the nonadiabatic phenomena taking
      place during tunnel ionization of atoms in strong laser fields to the
      radiationless relaxation through conical intersections and the nonadiabatic
      coupling of vibrational modes and discuss the computational approaches that have
      been developed to describe such phenomena. These methods range from the full
      solution of the combined nuclear-electronic quantum problem to a hierarchy of
      semiclassical approaches and even purely classical frameworks. The power of these
      simulation tools is illustrated by representative applications and the direct
      confrontation with experimental measurements performed in the National Centre of
      Competence for Molecular Ultrafast Science and Technology.

PMID- 29376111
TI  - Efficient Sum of Outer Products Dictionary Learning (SOUP-DIL) and Its
      Application to Inverse Problems.
AB  - The sparsity of signals in a transform domain or dictionary has been exploited in
      applications such as compression, denoising and inverse problems. More recently,
      data-driven adaptation of synthesis dictionaries has shown promise compared to
      analytical dictionary models. However, dictionary learning problems are typically
      non-convex and NP-hard, and the usual alternating minimization approaches for
      these problems are often computationally expensive, with the computations
      dominated by the NP-hard synthesis sparse coding step. This paper exploits the
      ideas that drive algorithms such as K-SVD, and investigates in detail efficient
      methods for aggregate sparsity penalized dictionary learning by first
      approximating the data with a sum of sparse rank-one matrices (outer products)
      and then using a block coordinate descent approach to estimate the unknowns. The
      resulting block coordinate descent algorithms involve efficient closed-form
      solutions. Furthermore, we consider the problem of dictionary-blind image
      reconstruction, and propose novel and efficient algorithms for adaptive image
      reconstruction using block coordinate descent and sum of outer products
      methodologies. We provide a convergence study of the algorithms for dictionary
      learning and dictionary-blind image reconstruction. Our numerical experiments
      show the promising performance and speedups provided by the proposed methods over
      previous schemes in sparse data representation and compressed sensing-based image
      reconstruction.

PMID- 29376110
TI  - Documentation of Contraception and Pregnancy Intention In Medicaid Managed Care.
AB  - Context: Clinical guidelines recommend the documentation of pregnancy intention
      and family planning needs during primary care visits. Prior to the 2014 Medicaid
      expansion and release of these guidelines, the documentation practices of
      Medicaid managed care providers are unknown. Methods: We performed a chart review
      of 1054 Medicaid managed care visits of women aged 13 to 49 to explore client,
      provider, and visit characteristics associated with documentation of immediate or
      future plans for having children and contraceptive method use. Five managed care
      plans used Current Procedural Terminology and International Classificationof
      Diseases, Ninth Revision codes to identify providers with at least 15 women who
      had received family planning or well-woman care in 2013. We conducted multilevel
      logistic regression analyses with documentation of contraceptive method and
      pregnancy intention as outcome variables and clinic site as the level 2 random
      effect. Results: Only 12% of charts had documentation of pregnancy intention and
      59% documented contraceptive use. Compared to women with a family planning visit
      reason, women with an annual, reproductive health, or primary care reason for
      their visit were significantly less likely to have contraception documented (odds
      ratio [OR] = 11.0; 95% confidence interval [CI] = 6.8-17.7). Age was also a
      significant predictor with women aged 30 to 49 (OR = 0.6; 95% CI = 0.4-0.9), and
      women aged 13 to 19 (OR = 0.2; 95% CI = 0.1-0.6) being less likely to have a note
      about pregnancy intention in their chart. Pregnancy intention was more likely to
      be documented in multispecialty clinics (OR = 15.5; 95% CI = 2.7-89.2).
      Conclusions: Interventions to improve routine medical record documentation of
      contraception and pregnancy intention regardless of patient age and visit
      characteristics are needed to facilitate the provision of family planning in
      managed care visits and, ultimately, achieving better maternal infant health
      outcomes and reduced costs.

PMID- 29376113
TI  - Major Gross Lesions of Lung in Cattle Slaughtered at Hawassa Municipal Abattoir,
      Southern Ethiopia.
AB  - A cross-sectional study was conducted from November 2016 to April 2017, to
      estimate the prevalence of major gross lung lesions in cattle slaughtered at
      Hawassa Municipal Abattoir, southern Ethiopia. A total of 563 male cattle were
      examined by antemortem examination, while postmortem lung lesions were done using
      standard inspection procedures. Association between prevalence and the
      explanatory variables was estimated by way of chi-square/Fischer's exact tests
      using statistical packages for social science (SPSS) software. Upon postmortem
      examination, 96.6% (544/563) of cattle examined had various gross lung lesions.
      The most important lesions identified were hydatidosis, emphysema, congestion,
      and atelectasis with prevalence of 45.3%, 19.2%, 18.1%, and 6.4%, respectively.
      Based on origins of slaughtered animals, hydatid cyst, emphysema, and congestion
      were common in cattle that came from Tula area with prevalence of 46.3%, 20.4%,
      and 20%, respectively. The animals from Arsi-negelle and Hawassa were mostly
      affected by hydatid cyst with prevalence of 44.4% and 42.5%, respectively.
      Statistically significant association (p = .038) was observed between prevalence
      of atelectasis and body condition of slaughtered cattle. In conclusion, the
      prevalence of hydatidosis was the major lesion in the lung of slaughtered cattle
      at Hawassa Municipal Abattoir. Therefore, appropriate disease control strategies
      should be put in place.

PMID- 29376109
TI  - Perspective: Opportunities for ultrafast science at SwissFEL.
AB  - We present the main specifications of the newly constructed Swiss Free Electron
      Laser, SwissFEL, and explore its potential impact on ultrafast science. In light
      of recent achievements at current X-ray free electron lasers, we discuss the
      potential territory for new scientific breakthroughs offered by SwissFEL in
      Chemistry, Biology, and Materials Science, as well as nonlinear X-ray science.

PMID- 29376112
TI  - Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for
      children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma
      (ANBL00P3): a randomised, open-label, phase 3 trial.
AB  - Purpose: No previous clinical trial has been conducted for patients with
      neuroblastoma associated opsoclonus myoclonus ataxia syndrome (OMA), and current
      treatment is based on case reports. To evaluate the OMA response to prednisone
      and risk-adapted chemotherapy and determine if the addition of intravenous
      gammaglobulin (IVIG) further improves response, the Children's Oncology Group
      designed a randomized therapeutic trial. Patient and Methods: Eligible subjects
      were randomized to receive twelve cycles of IVIG (IVIG+) or no IVIG (NO-IVIG) in
      addition to prednisone and neuroblastoma risk-adapted chemotherapy. All low-risk
      patients were treated with cyclophosphamide. The severity of OMA symptoms was
      evaluated at 2, 6, and 12 months using a scale developed by Mitchell and Pike and
      baseline versus best response scores were compared. A single patient who did not
      undergo neurologic assessment was excluded from OMA response analysis. This study
      is registered with Clinical Trials.gov (identifier NCT00033293). Results: Of the
      53 patients enrolled in the study, 62% (33/53) were female. There were 44 low
      risk, 7 intermediate-risk, and 2 high-risk neuroblastoma patients. Twenty-six
      subjects were randomized to receive IVIG+ and 27 were randomized to NO-IVIG. The
      neuroblastoma 3-year event-free survival (95% confidence interval (CI)) was 94.1%
      (87.3%, 100%) and overall survival was 98.0% (94.1%, 100%). Significantly higher
      rates of OMA response were observed in patients randomized to IVIG+ compared to
      NO-IVIG [21/26=80.8% for IVIG+; 11/27=40.7% for NO-IVIG (odds ratio=6.1; 95% CI:
      (1.5, 25.9), p=0.0029)]. For the majority of patients, the IVIG+ OMA regimen
      combined with cytoxan or other risk-based chemotherapy was well tolerated,
      although there was one toxic death in a high-risk subject. Conclusion: This is
      the only randomized prospective therapeutic clinical trial in children with
      neuroblastoma-associated OMA. The addition of IVIG to prednisone and risk-adapted
      chemotherapy significantly improves OMA response rate. IVIG+ constitutes a back
      bone upon which to build additional therapy.

PMID- 29376114
TI  - Korean Sibling Caregivers of Individuals Diagnosed with Schizophrenia.
AB  - Siblings of individuals diagnosed with schizophrenia are an important source of
      family caregiving. Unfortunately, limited information is available about sibling
      caregivers because existing studies have focused on other family relationships
      such as parents, spouses, and children. To fill the knowledge gap, the purpose of
      this study is to describe Korean sibling caregivers' experience with individuals
      diagnosed with schizophrenia. Guided by Colaizzi's descriptive phenomenological
      methodology, we conducted in-depth, semi-structured, face-to-face interviews with
      eight individuals who have a sibling (1) diagnosed with schizophrenia and (2)
      hospitalized in an inpatient psychiatric unit. We discerned six key themes:
      sorrow, burnout, shame, different perspectives in life, acceptance, and
      responsibility. We categorized these themes into three groups: suffering, hope,
      and responsibility and obligation. Sibling caregivers of individuals with
      schizophrenia experience a mixture of several emotions. Participants loved their
      brother or sister with schizophrenia, but at the same time they felt shame and
      fear. While they were burdened by the responsibilities of caregiving, they
      remained loyal to their sibling with schizophrenia, continuing to help their
      siblings reach their full potential. Although participants were confused about
      the symptoms of schizophrenia, they were committed to learning more about the
      illness. Because we conducted the current study in Korea, the findings of this
      study may be unique to Korea culture. Further studies are needed to compare and
      contrast nuanced differences in sibling caregivers' experience among different
      cultural groups.

PMID- 29376115
TI  - The Association of Departmental Quality Infrastructure and Positive Change: A
      Pathology Department Illustration.
AB  - A vertically and horizontally well-integrated quality improvement team is
      essential for effective quality data collection and implementation of improvement
      measures. We outline the quality structure of a large academic pathology
      department and describe successful projects across multiple divisions made
      possible by this tightly integrated structure. The physician vice chair for
      quality organizes departmental quality efforts and provides representation at the
      hospital level. The department has an independent continuous quality improvement
      unit and each laboratory of the department has a staff quality improvement
      representative. Faculty and staff experts have interacted to produce improvements
      such as accurate container labeling, efficient triage of specimens, and reduction
      of unnecessary testing. Specialized task forces such as the Courier Task Force
      are producing concrete recommendations for process improvement. All phases of
      pathology patient care are represented by faculty and staff who are trained in
      quality improvement, and each position touches and communicates actively with
      levels above and below itself. The key to the department's approach has been the
      daily attention to quality efforts in all of its activities and the close
      association of faculty and staff to accomplish the goals of greater efficiency,
      safety, and cost savings.

PMID- 29376116
TI  - Conflicts of interest improve collective computation of adaptive social
      structures.
AB  - In many biological systems, the functional behavior of a group is collectively
      computed by the system's individual components. An example is the brain's ability
      to make decisions via the activity of billions of neurons. A long-standing puzzle
      is how the components' decisions combine to produce beneficial group-level
      outputs, despite conflicts of interest and imperfect information. We derive a
      theoretical model of collective computation from mechanistic first principles,
      using results from previous work on the computation of power structure in a
      primate model system. Collective computation has two phases: an information
      accumulation phase, in which (in this study) pairs of individuals gather
      information about their fighting abilities and make decisions about their
      dominance relationships, and an information aggregation phase, in which these
      decisions are combined to produce a collective computation. To model information
      accumulation, we extend a stochastic decision-making model-the leaky integrator
      model used to study neural decision-making-to a multiagent game-theoretic
      framework. We then test alternative algorithms for aggregating information-in
      this study, decisions about dominance resulting from the stochastic model-and
      measure the mutual information between the resultant power structure and the
      "true" fighting abilities. We find that conflicts of interest can improve
      accuracy to the benefit of all agents. We also find that the computation can be
      tuned to produce different power structures by changing the cost of waiting for a
      decision. The successful application of a similar stochastic decision-making
      model in neural and social contexts suggests general principles of collective
      computation across substrates and scales.

PMID- 29376117
TI  - Reconfigurable nanoscale spin-wave directional coupler.
AB  - Spin waves, and their quanta magnons, are prospective data carriers in future
      signal processing systems because Gilbert damping associated with the spin-wave
      propagation can be made substantially lower than the Joule heat losses in
      electronic devices. Although individual spin-wave signal processing devices have
      been successfully developed, the challenging contemporary problem is the
      formation of two-dimensional planar integrated spin-wave circuits. Using both
      micromagnetic modeling and analytical theory, we present an effective solution of
      this problem based on the dipolar interaction between two laterally adjacent
      nanoscale spin-wave waveguides. The developed device based on this principle can
      work as a multifunctional and dynamically reconfigurable signal directional
      coupler performing the functions of a waveguide crossing element, tunable power
      splitter, frequency separator, or multiplexer. The proposed design of a spin-wave
      directional coupler can be used both in digital logic circuits intended for spin
      wave computing and in analog microwave signal processing devices.

PMID- 29376118
TI  - Sedimentary sulfur isotopes and Neoarchean ocean oxygenation.
AB  - Abrupt disappearance of mass-independent fractionation of sulfur isotopes (MIF-S)
      from the geologic record and an apparent ingrowth in seawater sulfate around 2.45
      billion years ago (Ga) signal the first large-scale oxygenation of the atmosphere
      [the Great Oxygenation Event (GOE)]. Pre-GOE O2 production is evident from
      multiple other terrestrial and marine proxies, but oceanic O2 concentrations
      remain poorly constrained. Furthermore, current interpretations of S isotope
      records do not explain a concurrent expansion in the range of both MIF-S
      diagnostic for low atmospheric O2-and delta34S beginning at 2.7 Ga. To address
      these unknowns, we developed a reaction-transport model to analyze the
      preservation patterns of sulfur isotopes in Archean sedimentary pyrites, one of
      the most robust and widely distributed proxies for early Earth biogeochemistry.
      Our modeling, paradoxically, reveals that micromolar levels of O2 in seawater
      enhance the preservation of large MIF-S signals, whereas concomitant ingrowth of
      sulfate expands the ranges in pyrite delta34S. The 2.7- to 2.45-Ga expansion in
      both Delta33S and delta34S ranges thus argues for a widespread and protracted
      oxygenation of seawater, at least in shallow marine environments. At the
      micromolar levels predicted, the surface oceans would support a strong flux of O2
      to the atmosphere, where O2 sinks balanced these fluxes until the GOE. This
      microoxic seawater would have provided habitat for early aerobic microorganisms
      and supported a diversity of new O2-driven biogeochemical cycles in the
      Neoarchean.

PMID- 29376119
TI  - Late formation of silicon carbide in type II supernovae.
AB  - We have found that individual presolar silicon carbide (SiC) dust grains from
      supernovae show a positive correlation between 49Ti and 28Si excesses, which is
      attributed to the radioactive decay of the short-lived (t1/2 = 330 days) 49V to
      49Ti in the inner highly 28Si-rich Si/S zone. The 49V-49Ti chronometer shows that
      these supernova SiC dust grains formed at least 2 years after their parent stars
      exploded. This result supports recent dust condensation calculations that predict
      a delayed formation of carbonaceous and SiC grains in supernovae. The
      astronomical observation of continuous buildup of dust in supernovae over several
      years can, therefore, be interpreted as a growing addition of C-rich dust to the
      dust reservoir in supernovae.

PMID- 29376120
TI  - Saigas on the brink: Multidisciplinary analysis of the factors influencing mass
      mortality events.
AB  - In 2015, more than 200,000 saiga antelopes died in 3 weeks in central Kazakhstan.
      The proximate cause of death is confirmed as hemorrhagic septicemia caused by the
      bacterium Pasteurella multocida type B, based on multiple strands of evidence.
      Statistical modeling suggests that there was unusually high relative humidity and
      temperature in the days leading up to the mortality event; temperature and
      humidity anomalies were also observed in two previous similar events in the same
      region. The modeled influence of environmental covariates is consistent with
      known drivers of hemorrhagic septicemia. Given the saiga population's
      vulnerability to mass mortality and the likely exacerbation of climate-related
      and environmental stressors in the future, management of risks to population
      viability such as poaching and viral livestock disease is urgently needed, as
      well as robust ongoing veterinary surveillance. A multidisciplinary approach is
      needed to research mass mortality events under rapid environmental change.

PMID- 29376121
TI  - Magnetosensitive e-skins with directional perception for augmented reality.
AB  - Electronic skins equipped with artificial receptors are able to extend our
      perception beyond the modalities that have naturally evolved. These synthetic
      receptors offer complimentary information on our surroundings and endow us with
      novel means of manipulating physical or even virtual objects. We realize highly
      compliant magnetosensitive skins with directional perception that enable magnetic
      cognition, body position tracking, and touchless object manipulation. Transfer
      printing of eight high-performance spin valve sensors arranged into two
      Wheatstone bridges onto 1.7-MUm-thick polyimide foils ensures mechanical
      imperceptibility. This resembles a new class of interactive devices extracting
      information from the surroundings through magnetic tags. We demonstrate this
      concept in augmented reality systems with virtual knob-turning functions and the
      operation of virtual dialing pads, based on the interaction with magnetic fields.
      This technology will enable a cornucopia of applications from navigation, motion
      tracking in robotics, regenerative medicine, and sports and gaming to interaction
      in supplemented reality.

PMID- 29376122
TI  - The accuracy, fairness, and limits of predicting recidivism.
AB  - Algorithms for predicting recidivism are commonly used to assess a criminal
      defendant's likelihood of committing a crime. These predictions are used in
      pretrial, parole, and sentencing decisions. Proponents of these systems argue
      that big data and advanced machine learning make these analyses more accurate and
      less biased than humans. We show, however, that the widely used commercial risk
      assessment software COMPAS is no more accurate or fair than predictions made by
      people with little or no criminal justice expertise. We further show that a
      simple linear predictor provided with only two features is nearly equivalent to
      COMPAS with its 137 features.

PMID- 29376123
TI  - The evolution of modern human brain shape.
AB  - Modern humans have large and globular brains that distinguish them from their
      extinct Homo relatives. The characteristic globularity develops during a prenatal
      and early postnatal period of rapid brain growth critical for neural wiring and
      cognitive development. However, it remains unknown when and how brain globularity
      evolved and how it relates to evolutionary brain size increase. On the basis of
      computed tomographic scans and geometric morphometric analyses, we analyzed
      endocranial casts of Homo sapiens fossils (N = 20) from different time periods.
      Our data show that, 300,000 years ago, brain size in early H. sapiens already
      fell within the range of present-day humans. Brain shape, however, evolved
      gradually within the H. sapiens lineage, reaching present-day human variation
      between about 100,000 and 35,000 years ago. This process started only after other
      key features of craniofacial morphology appeared modern and paralleled the
      emergence of behavioral modernity as seen from the archeological record. Our
      findings are consistent with important genetic changes affecting early brain
      development within the H. sapiens lineage since the origin of the species and
      before the transition to the Later Stone Age and the Upper Paleolithic that mark
      full behavioral modernity.

PMID- 29376124
TI  - Computational discovery of extremal microstructure families.
AB  - Modern fabrication techniques, such as additive manufacturing, can be used to
      create materials with complex custom internal structures. These engineered
      materials exhibit a much broader range of bulk properties than their base
      materials and are typically referred to as metamaterials or microstructures.
      Although metamaterials with extraordinary properties have many applications,
      designing them is very difficult and is generally done by hand. We propose a
      computational approach to discover families of microstructures with extremal
      macroscale properties automatically. Using efficient simulation and sampling
      techniques, we compute the space of mechanical properties covered by physically
      realizable microstructures. Our system then clusters microstructures with common
      topologies into families. Parameterized templates are eventually extracted from
      families to generate new microstructure designs. We demonstrate these
      capabilities on the computational design of mechanical metamaterials and present
      five auxetic microstructure families with extremal elastic material properties.
      Our study opens the way for the completely automated discovery of extremal
      microstructures across multiple domains of physics, including applications
      reliant on thermal, electrical, and magnetic properties.

PMID- 29376125
TI  - Thin films of topological Kondo insulator candidate SmB6: Strong spin-orbit
      torque without exclusive surface conduction.
AB  - The advent of topological insulators (TIs), a novel class of materials that
      harbor a metallic spin-chiral surface state coexisting with band-insulating bulk,
      opens up new possibilities for spintronics. One promising route is current
      induced switching of an adjacent magnetic layer via spin-orbit torque (SOT),
      arising from the large spin-orbit coupling intrinsically possessed by TIs. The
      Kondo insulator SmB6 has been recently proposed to be a strongly correlated TI,
      supported by the observation of a metallic surface state in bulk SmB6, as
      evidenced by the thickness independence of the low-temperature resistance
      plateau. We report the synthesis of epitaxial (001) SmB6/Si thin films and a
      systematic thickness-dependent electrical transport study. Although the low
      temperature resistance plateau is observed for all films from 50 to 500 nm in
      thickness, the resistance is distinctively thickness-dependent and does not
      support the notion of surface conduction and interior insulation. On the other
      hand, we demonstrate that SmB6 can generate a large SOT to switch an adjacent
      ferromagnetic layer, even at room temperature. The effective SOT generated from
      SmB6 is comparable to that from beta-W, one of the strongest SOT materials.

PMID- 29376127
TI  - Patient Planning and Initiative Enhances Physician Recommendations for Cancer
      Screening and Prevention.
AB  - Background: The growing population of older adults is at the highest risk for
      cancer, yet they are underserved in terms of cancer prevention and care.
      Discussions between patients and physicians that result in tailored
      recommendations are now called for by the U.S. Preventive Services Task Force.
      Aims & Method: The current study explored the role of physician-patient
      relationships and of patient initiatives in health communication on primary care
      physicians' recommendations of cancer prevention and screening. Our data was
      collected from baseline questionnaires from elderly patients 60 years of age or
      older (N=360) who attended an adult community center where an educational
      intervention was administered. Results: Our findings demonstrate the importance
      of elderly patients' advocacy, shown through planning and initiative in
      communication for eliciting doctor's cancer screening and cancer prevention
      recommendations in primary care settings.

PMID- 29376126
TI  - Oil for the cancer engine: The cross-talk between oncogenic signaling and
      polyamine metabolism.
AB  - The study of metabolism has provided remarkable information about the biological
      basis and therapeutic weaknesses of cancer cells. Classic biochemistry
      established the importance of metabolic alterations in tumor biology and revealed
      the importance of various metabolite families to the tumorigenic process. We have
      evidence of the central role of polyamines, small polycatonic metabolites, in
      cell proliferation and cancer growth from these studies. However, how cancer
      cells activate this metabolic pathway and the molecular cues behind the oncogenic
      action of polyamines has remained largely obscure. In contrast to the view of
      metabolites as fuel (anabolic intermediates) for cancer cells, polyamines are
      better defined as the oil that lubricates the cancer engine because they affect
      the activity of biological processes. Modern research has brought back to the
      limelight this metabolic pathway, providing a strong link between genetic,
      metabolic, and signaling events in cancer. In this review, we enumerate and
      discuss current views of the regulation and activity of polyamine metabolism in
      tumor cell biology.

PMID- 29376128
TI  - The complete mitochondrial genome of a skipper Burara striata (Lepidoptera:
      Hesperiidae).
AB  - We assembled a complete mitogenome of an Asian skipper butterfly Burara striata
      (Hesperiidae, Coeliadinae), the first representative of the genus Burara, from
      next generation sequencing reads. The 15327 bp mitogenome covers 13 protein
      coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes
      (rRNAs), and an A+T rich region. Its gene order is typical for mitogenomes of
      Lepidoptera. Phylogenetic analysis places Burara striata as a sister to Hasora,
      and Choaspes as a sister to both of these genera.

PMID- 29376129
TI  - BioTM Buzz (Volume 3, Issue 1).

PMID- 29376130
TI  - Ionic liquids for addressing unmet needs in healthcare.
AB  - Advances in the field of ionic liquids have opened new applications beyond their
      traditional use as solvents into other fields especially healthcare. The broad
      chemical space, rich with structurally diverse ions, and coupled with the
      flexibility to form complementary ion pairs enables task-specific optimization at
      the molecular level to design ionic liquids for envisioned functions.
      Consequently, ionic liquids now are tailored as innovative solutions to address
      many problems in medicine. To date, ionic liquids have been designed to promote
      dissolution of poorly soluble drugs and disrupt physiological barriers to
      transport drugs to targeted sites. Also, their antimicrobial activity has been
      demonstrated and could be exploited to prevent and treat infectious diseases.
      Metal-containing ionic liquids have also been designed and offer unique features
      due to incorporation of metals. Here, we review application-driven investigations
      of ionic liquids in medicine with respect to current status and future potential.

PMID- 29376131
TI  - RNA-Peptide nanoplexes drug DNA damage pathways in high-grade serous ovarian
      tumors.
AB  - DNA damaging chemotherapy is a cornerstone of current front-line treatments for
      advanced ovarian cancer (OC). Despite the fact that a majority of these patients
      initially respond to therapy, most will relapse with chemo-resistant disease;
      therefore, adjuvant treatments that synergize with DNA-damaging chemotherapy
      could improve treatment outcomes and survival in patients with this deadly
      disease. Here, we report the development of a nanoscale peptide-nucleic acid
      complex that facilitates tumor-specific RNA interference therapy to
      chemosensitize advanced ovarian tumors to frontline platinum/taxane therapy. We
      found that the nanoplex-mediated silencing of the protein kinase, MK2, profoundly
      sensitized mouse models of high-grade serous OC to cytotoxic chemotherapy by
      blocking p38/MK2-dependent cell cycle checkpoint maintenance. Combined RNAi
      therapy improved overall survival by 37% compared with platinum/taxane
      chemotherapy alone and decreased metastatic spread to the lungs without
      observable toxic side effects. These findings suggest (a) that peptide nanoplexes
      can serve as safe and effective delivery vectors for siRNA and (b) that combined
      inhibition of MK2 could improve treatment outcomes in patients currently
      receiving frontline chemotherapy for advanced OC.

PMID- 29376132
TI  - Visible light crosslinkable human hair keratin hydrogels.
AB  - Keratins extracted from human hair have emerged as a promising biomaterial for
      various biomedical applications, partly due to their wide availability, low cost,
      minimal immune response, and the potential to engineer autologous tissue
      constructs. However, the fabrication of keratin-based scaffolds typically relies
      on limited crosslinking mechanisms, such as via physical interactions or
      disulfide bond formation, which are time-consuming and result in relatively poor
      mechanical strength and stability. Here, we report the preparation of
      photocrosslinkable keratin-polyethylene glycol (PEG) hydrogels via the thiol
      norbornene "click" reaction, which can be formed within one minute upon
      irradiation of visible light. The resulting keratin-PEG hydrogels showed highly
      tunable mechanical properties of up to 45 kPa in compressive modulus, and long
      term stability in buffer solutions and cell culture media. These keratin-based
      hydrogels were tested as cell culture substrates in both two-dimensional surface
      seeding and three-dimensional cell encapsulation, demonstrating excellent
      cytocompatibility to support the attachment, spreading, and proliferation of
      fibroblast cells. Moreover, the photocrosslinking mechanism makes keratin-based
      hydrogel suitable for various microfabrication techniques, such as
      micropatterning and wet spinning, to fabricate cell-laden tissue constructs with
      different architectures. We believe that the unique features of this
      photocrosslinkable human hair keratin hydrogel promise new opportunities for
      their future biomedical applications.

PMID- 29376133
TI  - Schedule dependent synergy of gemcitabine and doxorubicin: Improvement of in
      vitro efficacy and lack of in vitro-in vivo correlation.
AB  - Combination chemotherapy is commonly used to treat late stage cancer; however,
      treatment is often limited by systemic toxicity. Optimizing drug ratio and
      schedule can improve drug combination activity and reduce dose to lower toxicity.
      Here, we identify gemcitabine (GEM) and doxorubicin (DOX) as a synergistic drug
      pair in vitro for the triple negative breast cancer cell line MDA-MB-231. Drug
      synergy and caspase activity were increased the most by exposing cells to GEM
      prior to DOX in vitro. While the combination was more effective than the single
      drugs at inhibiting MDA-MB-231 growth in vivo, the clear schedule dependence
      observed in vitro was not observed in vivo. Differences in drug exposure and
      cellular behavior in vivo compared to in vitro are likely responsible. This study
      emphasizes the importance in understanding how schedule impacts drug synergy and
      the need to develop more advanced strategies to translate synergy to the clinic.

PMID- 29376135
TI  - Using Collaborative Simulation Modeling to Develop a Web-Based Tool to Support
      Policy-Level Decision Making About Breast Cancer Screening Initiation Age.
AB  - Background: There are no publicly available tools designed specifically to assist
      policy makers to make informed decisions about the optimal ages of breast cancer
      screening initiation for different populations of US women. Objective: To use
      three established simulation models to develop a web-based tool called Mammo
      OUTPuT. Methods: The simulation models use the 1970 US birth cohort and common
      parameters for incidence, digital screening performance, and treatment effects.
      Outcomes include breast cancers diagnosed, breast cancer deaths averted, breast
      cancer mortality reduction, false-positive mammograms, benign biopsies, and
      overdiagnosis. The Mammo OUTPuT tool displays these outcomes for combinations of
      age at screening initiation (every year from 40 to 49), annual versus biennial
      interval, lifetime versus 10-year horizon, and breast density, compared to
      waiting to start biennial screening at age 50 and continuing to 74. The tool was
      piloted by decision makers (n = 16) who completed surveys. Results: The tool
      demonstrates that benefits in the 40s increase linearly with earlier initiation
      age, without a specific threshold age. Likewise, the harms of screening increase
      monotonically with earlier ages of initiation in the 40s. The tool also shows
      users how the balance of benefits and harms varies with breast density. Surveys
      revealed that 100% of users (16/16) liked the appearance of the site; 94% (15/16)
      found the tool helpful; and 94% (15/16) would recommend the tool to a colleague.
      Conclusions: This tool synthesizes a representative subset of the most current
      CISNET (Cancer Intervention and Surveillance Modeling Network) simulation model
      outcomes to provide policy makers with quantitative data on the benefits and
      harms of screening women in the 40s. Ultimate decisions will depend on program
      goals, the population served, and informed judgments about the weight of benefits
      and harms.

PMID- 29376134
TI  - Engineering of a miniaturized, robotic clinical laboratory.
AB  - The ability to perform laboratory testing near the patient and with smaller blood
      volumes would benefit patients and physicians alike. We describe our design of a
      miniaturized clinical laboratory system with three components: a hardware
      platform (ie, the miniLab) that performs preanalytical and analytical processing
      steps using miniaturized sample manipulation and detection modules, an assay
      configurable cartridge that provides consumable materials and assay reagents, and
      a server that communicates bidirectionally with the miniLab to manage assay
      specific protocols and analyze, store, and report results (i.e., the virtual
      analyzer). The miniLab can detect analytes in blood using multiple methods,
      including molecular diagnostics, immunoassays, clinical chemistry, and
      hematology. Analytical performance results show that our qualitative Zika virus
      assay has a limit of detection of 55 genomic copies/ml. For our anti-herpes
      simplex virus type 2 immunoglobulin G, lipid panel, and lymphocyte subset panel
      assays, the miniLab has low imprecision, and method comparison results agree well
      with those from the United States Food and Drug Administration-cleared devices.
      With its small footprint and versatility, the miniLab has the potential to
      provide testing of a range of analytes in decentralized locations.

PMID- 29376136
TI  - Clinical and molecular sub-classification of hepatocellular carcinoma relative to
      alpha-fetoprotein level in an Asia-Pacific island cohort.
AB  - Aim: Increased serum alpha-fetoprotein (AFP) levels are associated with specific
      molecular sub-classes of hepatocellular carcinoma (HCC), supporting AFP as a
      predictive or therapeutic biomarker for precision treatment of this disease.
      Considering recent efforts to validate HCC molecular classification systems
      across different populations, we applied existing signature-based classification
      templates to Hawaii cohorts and examined whether associations between HCC
      molecular sub-class, AFP levels, and clinical features found elsewhere can also
      be found in Hawaii, a region with a unique demographic and risk factor profile
      for HCC. Methods: Whole-genome expression profiling was performed on HCC tumors
      collected from 40 patients following partial hepatectomy. Tumors underwent
      transcriptome-based categorization into 3 molecular sub-classes (S1, S2, and S3).
      Patient groups based on molecular sub-class and AFP level were then compared with
      regards to clinical features and survival. Differences associated with AFP level
      and other clinical parameters were also examined at the gene signature level by
      gene set enrichment analysis. Results: Statistically confident (false discovery
      rate < 0.05) sub-classifications were made in 98% (39/40) of tumors. Patient sub
      groups differed significantly with regards to serum AFP level, with significantly
      lower levels in the S3 sub-group as compared to S1 (P = 0.048) and S2 (P =
      0.010). Serum AFP > 400 ng/mL predicted significant tumor enrichment for genes
      corresponding to MYC target activation, high cell proliferation, poor clinical
      prognosis, and the S2 sub-class. AFP > 400 ng/mL and non-S3 tumor classification
      were found to be significant predictors of overall survival. Conclusion: Distinct
      sub-classes of HCC associated with different molecular features and survival
      outcomes can be detected with statistical confidence in a Pacific Island cohort.
      Molecular classification signatures and other predictive markers for HCC that are
      valid for all patient populations are needed to support multi-center efforts to
      develop targeted therapies for HCC.

PMID- 29376137
TI  - The midwives service scheme: a qualitative comparison of contextual determinants
      of the performance of two states in central Nigeria.
AB  - Background: The federal government of Nigeria started the Midwives Service Scheme
      in 2009 to address the scarcity of skilled health workers in rural communities by
      temporarily redistributing midwives from urban to rural communities. The scheme
      was designed as a collaboration among federal, state and local governments. Six
      years on, this study examines the contextual factors that account for the
      differences in performance of the scheme in Benue and Kogi, two contiguous states
      in central Nigeria. Methods: We obtained qualitative data through 14 in-depth
      interviews and 2 focus group discussions: 14 government officials at the federal,
      state and local government levels were interviewed to explore their perceptions
      on the design, implementation and sustainability of the Midwives Service Scheme.
      In addition, mothers in rural communities participated in 2 focus group
      discussions (one in each state) to elicit their views on Midwives Service Scheme
      services. The qualitative data were analysed for themes. Results: The inability
      of the federal government to substantially influence the health care agenda of
      sub-national governments was a significant impediment to the achievement of the
      objectives of the Midwives Service Scheme. Participants identified differences in
      government prioritisation of primary health care between Benue and Kogi as
      relevant to maternal and child health outcomes in those states: Kogi was far more
      supportive of the Midwives Service Scheme and primary health care more broadly.
      High user fees in Benue was a significant barrier to the uptake of available
      maternal and child health services. Conclusion: Differential levels of political
      support and prioritisation, alongside financial barriers, contribute
      substantially to the uptake of maternal and child health services. For
      collaborative health sector strategies to gain sufficient traction, where
      federating units determine their health care priorities, they must be accompanied
      by strong and enforceable commitment by sub-national governments.

PMID- 29376138
TI  - Attributable risk and potential impact of interventions to reduce household air
      pollution associated with under-five mortality in South Asia.
AB  - Background: Solid fuel use is the major source of household air pollution (HAP)
      and accounts for a substantial burden of morbidity and mortality in low and
      middle income countries. To evaluate and compare childhood mortality attributable
      to HAP in four South Asian countries. Methods: A series of Demographic and Health
      Survey (DHS) datasets for Bangladesh, India, Nepal and Pakistan were used for
      analysis. Estimates of relative risk and exposure prevalence relating to use of
      cooking fuel and under-five mortality were used to calculate population
      attributable fractions (PAFs) for each country. Potential impact fractions (PIFs)
      were also calculated assessing theoretical scenarios based on published
      interventions aiming to reduce exposure prevalence. Results: There are an
      increased risk of under-five mortality in those exposed to cooking fuel compared
      to those not exposed in the four South Asian countries (OR = 1.30, 95% CI = 1.07
      1.57, P = 0.007). Combined PAF estimates for South Asia found that 66% (95% CI:
      43.1-81.5%) of the 13,290 estimated cases of under-five mortality was
      attributable to HAP. Joint PIF estimates (assuming achievable reductions in HAP
      reported in intervention studies conducted in South Asia) indicates 47% of
      neonatal and 43% of under-five mortality cases associated with HAP could be
      avoidable in the four South Asian countries studied. Conclusions: Elimination of
      exposure to use of cooking fuel in the household targeting valuable intervention
      strategies (such as cooking in separate kitchen, improved cook stoves) could
      reduce substantially under-five mortality in South Asian countries.

PMID- 29376139
TI  - Fishing for cures: The alLURE of using zebrafish to develop precision oncology
      therapies.
AB  - Zebrafish have proven to be a valuable model to study human cancer biology with
      the ultimate aim of developing new therapies. Danio rerio are amenable to in vivo
      imaging, high throughput drug screening, mutagenesis, and transgenesis, and they
      share histological and genetic similarities with Homo sapiens. The significance
      of zebrafish in the field of precision oncology is rapidly emerging. Indeed,
      modeling cancer in zebrafish has already been used to identify tumor biomarkers,
      define therapeutic targets and provide an in vivo platform for drug discovery.
      New zebrafish studies are starting to pave the way to direct individualized
      clinical applications. Patient-derived cancer cell xenograft models have
      demonstrated the feasibility of using zebrafish as a real time avatar of
      prognosis and drug response to identify the most ideal therapy for an individual
      patient. Genetic cancer modeling in zebrafish, now facilitated by rapidly
      evolving genome editing techniques, represents another innovative approach to
      recapitulate human oncogenesis and develop individualized treatments. Utilizing
      zebrafish to design customizable precision therapies will improve the clinical
      outcome of patients afflicted with cancer.

PMID- 29376140
TI  - Cost and Cost-Effectiveness Assessments of Newborn Screening for Critical
      Congenital Heart Disease Using Pulse Oximetry: A Review.
AB  - Screening newborns for critical congenital heart disease (CCHD) using pulse
      oximetry is recommended to allow for the prompt diagnosis and prevention of life
      threatening crises. The present review summarizes and critiques six previously
      published estimates of the costs or cost-effectiveness of CCHD screening from the
      United Kingdom, United States, and China. Several elements that affect CCHD
      screening costs were assessed in varying numbers of studies, including screening
      staff time, instrumentation, and consumables, as well as costs of diagnosis and
      treatment. A previous US study that used conservative assumptions suggested that
      CCHD screening is likely to be considered cost-effective from the healthcare
      sector perspective. Newly available estimates of avoided infant CCHD deaths in
      several US states that implemented mandatory CCHD screening policies during 2011
      2013 suggest a substantially larger reduction in deaths than was projected in the
      previous US cost-effectiveness analysis. Taking into account these new estimates,
      we estimate that cost per life-year gained could be as low as USD 12,000.
      However, that estimate does not take into account future costs of health care and
      education for surviving children with CCHD nor the costs incurred by health
      departments to support and monitor CCHD screening policies and programs.

PMID- 29376141
TI  - Physical Therapy Considerations for Chronic Kidney Disease and Secondary
      Sarcopenia.
AB  - Chronic kidney disease (CKD) is a progressive condition that may negatively
      affect musculoskeletal health. These comorbidities may include malnutrition,
      osteoporosis, and decreased lean body mass. Secondary sarcopenia due to CKD may
      be associated with mobility limitations and elevated fall risk. Physical
      therapists are well-positioned among the health care team to screen for secondary
      sarcopenia in those with CKD and for the treatment of musculoskeletal comorbid
      conditions that may affect functional performance. Given the consequences of both
      low muscle mass and low bone mineral density, appropriate and timely physical
      therapy is important for fall risk assessment and intervention to minimize the
      susceptibility to bone fracture. While strength training has been studied less
      frequently than aerobic training for the management of secondary CKD conditions,
      evidence suggests that this patient population benefits from participation in
      strength training programs. However, the provision of a formal exercise
      prescription by a health care professional, along with formal implementation of
      an exercise program, may need to be more fully integrated into the standard plan
      of care for individuals with CKD.

PMID- 29376142
TI  - Mapping the Chromatin State Dynamics in Myoblasts.
AB  - Background: Genome-wide mapping reveals chromatin landscapes unique to cell
      states. Histone marks of regulatory genes involved in cell specification and
      organ development provide a powerful tool to map regulatory sequences. H3K4me3
      marks promoter regions; H3K27me3 marks repressed regions, and Pol II presence
      indicates active transcription. The presence of both H3K4me3 and H3K27me3
      characterize poised sequences, a common characteristic of genes involved in
      pattern formation during organogenesis. Results: We used genome-wide profiling
      for H3K27me3, H3K4me3, and Pol II to map chromatin states in mouse embryonic day
      12 forelimbs in wild type (control) and Pitx2-null mutant mice. We compared these
      data with previous gene expression studies from forelimb Lbx1+ migratory
      myoblasts and correlated Pitx2-dependent expression profiles and chromatin
      states. During forelimb development, several lineages including myoblast,
      osteoblast, neurons, angioblasts etc., require synchronized growth to form a
      functional limb. We identified 125 genes in the developing forelimb that are
      Pitx2-dependent. Genes involved in muscle specification and cytoskeleton
      architecture were positively regulated, while genes involved in axonal path
      finding were poised. Conclusion: Our results have established histone
      modification profiles as a useful tool for identifying gene regulatory states in
      muscle development, and identified the role of Pitx2 in extending the time of
      myoblast progression, promoting formation of sarcomeric structures, and
      suppressing attachment of neuronal axons.

PMID- 29376143
TI  - Bevacizumab Injection in Patients with Neovascular Age-Related Macular
      Degeneration Increases Angiogenic Biomarkers.
AB  - Purpose: To evaluate the expression of 19 angiogenic biomarkers in the aqueous
      humor before and after intravitreal bevacizumab injection (IVB) in eyes with
      neovascular age-related macular degeneration (AMD). Design: Prospective,
      noncomparative, interventional case series. Participants: Twenty-three eyes of 23
      treatment-naive patients with choroidal neovascularization (CNV) secondary to
      neovascular AMD. Methods: Eyes were diagnosed with CNV secondary to neovascular
      AMD and were treated with 3 monthly IVBs. Aqueous humor samples were obtained by
      anterior chamber paracentesis at baseline and immediately before each
      intravitreal bevacizumab injection. Main Outcome Measures: Aqueous humor levels
      of 19 angiogenic biomarkers (angiopoietin 2, bone morphogenetic protein 9 [BMP
      9], epidermal growth factor [EGF], endoglin, endothelin 1, fibroblast growth
      factor [FGF]-1 and FGF-2, follistatin, granulocyte colony-stimulating factor
      [GCSF], heparin-binding EGF-like growth factor [HB-EGF], hepatocyte growth factor
      [HGF], interleukin 8, leptin, placental growth factor [PLGF], vascular
      endothelial growth factor [VEGF]-A, VEGF-C, VEGF-D, and tissue inhibitor of
      metalloproteinases [TIMP]-1 and TIMP-2) were measured. Best-corrected visual
      acuity (BCVA), spectral-domain OCT parameters, and intraocular pressure also were
      evaluated. Results: Baseline aqueous VEGF-A expression was elevated in all study
      eyes before treatment initiation. A statistically significant decrease of VEGF-A
      was observed at the 1- and 2-month follow-ups. A statistically significant
      increased concentration was observed in 7 biomarkers: VEGF-C, angiopoietin 2,
      endothelin 1, follistatin, HB-EGF, HGF, and interleukin 8. The other 11 study
      biomarker levels (VEGF-D, BMP-9, EGF, endoglin, FGF-1, FGF-2, GCSF, leptin, PLGF,
      TIMP-1, and TIMP-2) did not show any significant difference during follow-up. The
      BCVA statistically improved significantly at 2 months. Spectral-domain OCT
      parameters improved significantly at all follow-ups. Mean intraocular pressure
      values were not statistically different during the study period. Conclusions:
      Despite a decrease in VEGF-A, the aqueous levels of VEGF-C, angiopoietin 2,
      endothelin 1, follistatin, HB-EGF, HGF, and interleukin 8 increased significantly
      after intravitreal injection of bevacizumab. These upregulated angiogenic
      biomarkers may represent new therapeutic targets in exudative AMD.

PMID- 29376144
TI  - Tracking the Evolution of Resistance to ALK Tyrosine Kinase Inhibitors through
      Longitudinal Analysis of Circulating Tumor DNA.
AB  - Purpose: ALK rearrangements predict for sensitivity to ALK tyrosine kinase
      inhibitors (TKIs). However, responses to ALK TKIs are generally short-lived.
      Serial molecular analysis is an informative strategy for identifying genetic
      mediators of resistance. Although multiple studies support the clinical benefits
      of repeat tissue sampling, the clinical utility of longitudinal circulating tumor
      DNA analysis has not been established in ALK-positive lung cancer. Methods: Using
      a 566-gene hybrid-capture next-generation sequencing (NGS) assay, we performed
      longitudinal analysis of plasma specimens from 22 ALK-positive patients with
      acquired resistance to ALK TKIs to track the evolution of resistance during
      treatment. To determine tissue-plasma concordance, we compared plasma findings to
      results of repeat biopsies. Results: At progression, we detected an ALK fusion in
      plasma from 19 (86%) of 22 patients, and identified ALK resistance mutations in
      plasma specimens from 11 (50%) patients. There was 100% agreement between tissue-
      and plasma-detected ALK fusions. Among 16 cases where contemporaneous plasma and
      tissue specimens were available, we observed 100% concordance between ALK
      mutation calls. ALK mutations emerged and disappeared during treatment with
      sequential ALK TKIs, suggesting that plasma mutation profiles were dependent on
      the specific TKI administered. ALK G1202R, the most frequent plasma mutation
      detected after progression on a second-generation TKI, was consistently
      suppressed during treatment with lorlatinib. Conclusions: Plasma genotyping by
      NGS is an effective method for detecting ALK fusions and ALK mutations in
      patients progressing on ALK TKIs. The correlation between plasma ALK mutations
      and response to distinct ALK TKIs highlights the potential for plasma analysis to
      guide selection of ALK-directed therapies.

PMID- 29376145
TI  - The Role of Txnip in Mitophagy Dysregulation and Inflammasome Activation in
      Diabetic Retinopathy: A New Perspective.
AB  - Mitochondria are responsible for bioenergetics, metabolism and apoptosis signals
      in health and disease. The retina being a part of the central nervous system
      consumes large amounts of glucose and oxygen to generate ATP via the
      mitochondrial oxidative phosphorylation for its phototransduction and visual
      function. During ATP generation, electrons leak from the mitochondrial electron
      transport chain, which is captured by molecular oxygen to produce reactive oxygen
      species (ROS). These mtROS damage mitochondrial proteins, mtDNA, and membrane
      lipids and release them in the cytosol. Mitochondrial components are recognized
      as danger-associated molecular patterns (DAMPS) by cytosolic pattern recognition
      receptors such as NOD-like receptors, NLRP3 inflammasomes. They process pro
      caspase-1 to active caspase-1, which cleaves pro-inflammatory IL-1beta o mature
      IL-1beta causing inflammation and cell death by pyroptosis. To counter the
      damaging action of mtROS and inflammasomes in fully differentiated cells in the
      retina, the removal of the damaged and dysfunctional mitochondria by a double
      membrane autophagic process via lysosomal degradation called mitophagy is
      critical for mitochondrial homeostasis and cell survival. Nonetheless, under
      chronic diseases including diabetic retinopathy (DR), mitophagy dysregulation and
      NLRP3 inflammasome activation exist, which cause premature cell death and disease
      progression. Recently, the thioredoxin-interacting protein TXNIP, which is
      strongly induced by diabetes and inhibits anti-oxidant function of thioredoxin,
      has been implicated in mitochondrial dysfunction, mitophagic dysregulation and
      NLRP3 inflammasome activation in DR. Therefore, TXNIP silencing or
      pharmacological inhibition may normalize mitophagic flux and NLRP3 inflammasome
      activation, which will prevent or slow down the progression of DR.

PMID- 29376146
TI  - ADAMTS13 Deficiency Worsens Colitis and Exogenous ADAMTS13 Administration
      Decreases Colitis Severity in Mice.
AB  - Background: Inflammatory bowel disease (IBD) affects 1.6 million people in the
      United States. IBD is associated with an increased risk of thrombosis, which
      rises with disease activity. The pathogenesis of IBD and its increased thrombotic
      risk is not completely understood. Ultra large von Willebrand factor (ULVWF)
      multimers are secreted from activated endothelium, leading to recruitment of
      platelets and leukocytes. A disintegrin and metalloproteinase with thrombospondin
      type I repeats motif 13 (ADAMTS13) cleaves highly adhesive ULVWF into smaller,
      less bioactive, multimers, releasing them into circulation. Mice deficient in
      ADAMTS13 (ADAMTS13-/-) have heightened inflammatory and thrombotic responses.
      Objectives: We hypothesized that upon colitis induction, ADAMTS13-/- mice would
      have more severe symptoms compared with wild-type (WT) mice, and rhADAMTS13
      administration to mice with colitis would improve their condition. Results:
      Dextran sodium sulfate-induced colitis was worse in ADAMTS13-/- mice than WT.
      ADAMTS13-/- showed increased weight loss, worse anemia, and increased clinical
      and histologic colitis severity, compared with WT mice. ADAMTS13-/- mice had
      increased VWF release, with accumulation at inflamed colonic sites. Also, the
      majority of mice showed one or more submucosal colonic thrombi. ADAMTS13
      deficiency worsened colitis and propagated intestinal inflammation, most likely
      through increased platelet-leukocyte recruitment by VWF. Treatment of WT mice
      with rhA-DAMTS13 decreased colitis severity without worsening anemia.
      Additionally, several immune-mediated chronic murine colitis models, and inflamed
      colon tissue specimens from IBD patients, showed increased VWF release at
      inflamed sites, suggesting a generalizability of our findings. Conclusion:
      Measuring VWF/ADAMTS13 levels could have clinical utility. When applicable, the
      administration of ADAMTS13, in addition to primary treatment, may improve
      outcomes for IBD patients.

PMID- 29376147
TI  - Epigenetic Signature of Impaired Fasting Glucose in the Old Order Amish.
AB  - Introduction: Type 2 Diabetes (T2D) is a common chronic disease with substantial
      disease burden and economic impact. Lifestyle changes can significantly alter the
      course of the disease, if detected at an early stage. DNA methylation signature
      may serve as a biomarker for early detection of increased T2D risk. Design: DNA
      methylation profiling was performed using the Illumina Infinium Human Methylation
      450K Bead chip array in 24 normoglycemic Old Order Amish (OOA) individuals who
      later developed Impaired Fasting Glucose (IFG) (cases), and 24 OOA individuals
      who remained normoglycemic after an average follow up of 10 years (controls).
      Cases and controls were matched on age, sex, BMI, baseline fasting glucose, and
      glucose level after 2 h from 75 g Oral Glucose Tolerance Test (OGTT). Results:
      Association analysis found no significant difference in either global methylation
      or individual probe methylation between cases and controls, however, the top 34
      suggestive significant sites were located in genes with interesting biological
      links to T2D and glycemic traits. These genes include BTC that plays a role in
      pancreatic cell proliferation and insulin secretion, ITGA1 a known bone mineral
      density gene that was recently found to be associated also with T2D and glycemic
      traits, and may explain the link between T2D and BMD, and RPTOR and TSC2 both of
      which are part of insulin signaling pathway. Conclusions: These results may shed
      light on the initiation and development of hyperglycemia and T2D and help to
      identify high risk individuals for early intervention; however, further studies
      are required for validation.

PMID- 29376148
TI  - Decreasing HMGB1 levels improves outcome of Pseudomonas aeruginosa keratitis in
      mice.
AB  - Pseudomonas (P.) aeruginosa is a Gram negative bacterium widely dispersed in the
      environment which can cause acute and chronic infections in humans. According to
      the Centers for Disease Control and Prevention (CDC), the overall incidence of P.
      aeruginosa infections in USA hospitals averages about 0.4% (4/1000 discharges),
      and the bacterium is the fourth most commonly-isolated nosocomial pathogen
      accounting for 10.1% of all hospital-acquired infections. P. aeruginosa keratitis
      is a severe infection of the eye, progresses rapidly and remains a leading cause
      of corneal ulcers worldwide. Use of contact lenses is the major risk factor in
      the USA, while in less industrialized countries, trauma from agricultural
      accidents are of importance. Animal models of bacterial keratitis are of value in
      the study of this disease and suggest potential alternative therapeutic targets
      that are needed urgently due to increasing antibiotic resistance. Recently we
      have shown success and improved disease outcome after down-regulation of one
      promising target, high mobility group box1 (HMGB1) using small interfering RNA
      (siRNA). Testing more clinically relevant approaches are underway to reduce HMGB1
      levels in P. aeruginosa keratitis which may hold promise for its treatment.

PMID- 29376149
TI  - Feature Learning and Fusion of Multimodality Neuroimaging and Genetic Data for
      Multi-status Dementia Diagnosis.
AB  - In this paper, we aim to maximally utilize multimodality neuroimaging and genetic
      data to predict Alzheimer's disease (AD) and its prodromal status, i.e., a multi
      status dementia diagnosis problem. Multimodality neuroimaging data such as MRI
      and PET provide valuable insights to abnormalities, and genetic data such as
      Single Nucleotide Polymorphism (SNP) provide information about a patient's AD
      risk factors. When used in conjunction, AD diagnosis may be improved. However,
      these data are heterogeneous (e.g., having different data distributions), and
      have different number of samples (e.g., PET data is having far less number of
      samples than the numbers of MRI or SNPs). Thus, learning an effective model using
      these data is challenging. To this end, we present a novel three-stage deep
      feature learning and fusion framework , where the deep neural network is trained
      stage-wise. Each stage of the network learns feature representations for
      different combination of modalities, via effective training using maximum number
      of available samples . Specifically, in the first stage, we learn latent
      representations (i.e., high-level features) for each modality independently, so
      that the heterogeneity between modalities can be better addressed and then
      combined in the next stage. In the second stage, we learn the joint latent
      features for each pair of modality combination by using the high-level features
      learned from the first stage. In the third stage, we learn the diagnostic labels
      by fusing the learned joint latent features from the second stage. We have tested
      our framework on Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset for
      multi-status AD diagnosis, and the experimental results show that the proposed
      framework outperforms other methods.

PMID- 29376151
TI  - Visible light-mediated oxidative C(sp3)-H phosphonylation for alpha
      aminophosphonates under oxidant-free conditions.
AB  - An external oxidant-free synthesis of alpha-aminophosphonates by synergistically
      combining photocatalysis and proton-reduction catalysis is developed herein. The
      gram-scale experiment demonstrates the potential utility of this protocol. This
      study may have important implications for the functionalization of oxidant
      sensitive C(sp3)-H bonds.

PMID- 29376150
TI  - Joint Craniomaxillofacial Bone Segmentation and Landmark Digitization by Context
      Guided Fully Convolutional Networks.
AB  - Generating accurate 3D models from cone-beam computed tomography (CBCT) images is
      an important step in developing treatment plans for patients with
      craniomaxillofacial (CMF) deformities. This process often involves bone
      segmentation and landmark digitization. Since anatomical landmarks generally lie
      on the boundaries of segmented bone regions, the tasks of bone segmentation and
      landmark digitization could be highly correlated. However, most existing methods
      simply treat them as two standalone tasks, without considering their inherent
      association. In addition, these methods usually ignore the spatial context
      information (i.e., displacements from voxels to landmarks) in CBCT images. To
      this end, we propose a context-guided fully convolutional network (FCN) for joint
      bone segmentation and landmark digitization. Specifically, we first train an FCN
      to learn the displacement maps to capture the spatial context information in CBCT
      images. Using the learned displacement maps as guidance information, we further
      develop a multi-task FCN to jointly perform bone segmentation and landmark
      digitization. Our method has been evaluated on 107 subjects from two centers, and
      the experimental results show that our method is superior to the state-of-the-art
      methods in both bone segmentation and landmark digitization.

PMID- 29376152
TI  - Relay photocatalytic cascade reactions: synthesis of indolo[2,1-a]isoquinoline
      derivatives via double C(sp3)-H bond functionalization.
AB  - A relay photoredox catalysis strategy concomitant with [1,5] hydrogen atom
      transfer has been applied in the construction of a biologically important
      indolo[2,1-a]isoquinoline framework via a cascade reaction. This reaction enables
      double C(sp3)-H bond functionalization and formation of two carbon-carbon double
      bonds from readily available starting materials in an efficient and step
      economical manner.

PMID- 29376153
TI  - Anomalous fluorescence enhancement and fluorescence quenching of graphene quantum
      dots by single walled carbon nanotubes.
AB  - We explore the mechanism of the fluorescence enhancement and fluorescence
      quenching effect of single walled carbon nanotubes (SWCNTs) on highly fluorescent
      graphene quantum dots (GQDs) over a wide range of concentrations of SWCNTs. At
      very low concentrations of SWCNTs, the fluorescence intensity of the GQDs is
      enhanced, while at higher concentrations, systematic quenching of fluorescence is
      observed. The nature of the Stern-Volmer plot for the latter case was found to be
      non-linear indicating a combined effect of dynamic and static quenching. The
      contribution of the dynamic quenching component was assessed through the
      fluorescence lifetime measurements. The contribution of static quenching is
      confirmed from the red shift of the fluorescence spectra of the GQDs after
      addition of SWCNTs. The fluorescence intensity is first enhanced at very low
      concentration due to improved dispersion and higher absorption by GQDs, while at
      higher concentration, the fluorescence of GQDs is quenched due to the complex
      formation and associated reduction of the radiative sites of the GQDs, which is
      confirmed from time-resolved fluorescence measurements. Laser confocal microscopy
      imaging provides direct evidence of the enhancement and quenching of fluorescence
      at low and high concentrations of SWCNTs, respectively. This study provides an
      important insight into tuning the fluorescence of GQDs and understanding the
      interaction between GQDs and different CNTs, which is important for bio-imaging
      and drug delivery applications.

PMID- 29376154
TI  - Harvesting visible light with MoO3 nanorods modified by Fe(iii) nanoclusters for
      effective photocatalytic degradation of organic pollutants.
AB  - The photocatalytic performance of MoO3 is limited due to its weak visible light
      absorption ability and quick recombination of charge carriers. In the present
      work, we report the facile synthesis of Fe(iii)-grafted MoO3 nanorods using a
      hydrothermal method followed by an impregnation technique with the aim of
      enhancing the light harvesting ability and photocatalytic efficiency of MoO3. The
      prepared samples were characterized through the standard analytical techniques of
      XRD, SEM-EDS, TEM, XPS, UV-Vis-DRS, FT-IR, TG-DTA and PL spectrophotometry. XPS
      and TEM analyses reveal that Fe(iii) ions are successfully grafted onto the
      surface of the MoO3 nanorod with intimate interfacial contact. The photocatalytic
      performances of the prepared samples were investigated by studying the
      degradation of methylene blue (MB), rhodamine B (RhB) and 4-nitrophenol (4-NP)
      under visible light irradiation. The surface-modified MoO3 with Fe(iii) ions
      showed excellent photocatalytic activity towards the degradation of the above
      mentioned pollutants, where Fe(iii) ions act as effective cocatalytic sites to
      produce hydroxyl radicals through multi-electron reduction of oxygen molecules.
      The improved photocatalytic activity could be ascribed to the effective
      separation of charge carriers and efficient production of hydroxyl radicals via
      the rapid capture of electrons by Fe(iii) through a well-known photoinduced
      interfacial charge transfer mechanism. Based on scavenger analysis study, a
      mechanism for the enhanced photocatalytic activity has been discussed and
      proposed. The concept of surface grafting onto large bandgap semiconductors with
      ubiquitous elements opens up a new avenue for the development of visible-light
      responsive photocatalysts with excellent photocatalytic activity.

PMID- 29376155
TI  - Response of mercury in an Adirondack (NY, USA) forest stream to watershed lime
      application.
AB  - Surface waters in Europe and North America previously impacted by acid deposition
      are recovering in conjunction with declining precursor emissions since the 1980s.
      Lime has been applied to some impacted watersheds to accelerate recovery. The
      response to liming can be considered a proxy for future recovery from acid
      deposition. Increases in dissolved organic carbon concentrations have been
      observed in surface waters in response to increased pH associated with recovery
      from acid deposition. Although not previously described, recovery-related
      increases in dissolved organic carbon could drive increases in mercury
      concentrations and loads because of the affinity of mercury for dissolved organic
      matter. We used a before-after impact-response approach to describe the response
      of stream mercury cycling to the application of lime to the watershed of a small
      stream in the Adirondack Mountains of New York, USA. Dissolved organic carbon,
      total mercury and methylmercury concentrations increased significantly in
      streamwater within two weeks of treatment, to previously unobserved
      concentrations. After six months, post-treatment before-after impact-control
      (BACI) tests indicate that mean dissolved organic carbon concentrations and total
      mercury to dissolved organic carbon ratios remained significantly higher and
      limed site fluxes of methylmercury were lower than those at the reference stream.
      This pattern suggests total mercury is leaching at elevated levels from the limed
      watershed, but limitations in production and transport to the stream channel
      likely resulted in increases in methylmercury concentration that were of limited
      duration.

PMID- 29376156
TI  - Mussel-inspired graphene oxide nanosheet-enwrapped Ti scaffolds with drug
      encapsulated gelatin microspheres for bone regeneration.
AB  - Graphene oxide (GO) attracts considerable attention for biomedical applications
      owing to its unique nanostructure and remarkable physicochemical characteristics.
      However, it is challenging to uniformly deposit GO on chemically inert Ti
      scaffolds, which have good biocompatibility and wide applications in bone
      engineering. In this study, a GO-functionalized Ti porous scaffold (GO/Ti
      scaffold) was prepared by depositing GO onto polydopamine (PDA) modified Ti
      scaffolds. The mussel-inspired PDA modification facilitated the interaction
      between GO and Ti surfaces, leading to a uniform coverage of GO on Ti scaffolds.
      BMP2 and vancomycin (Van) were separately encapsulated into gelatin microspheres
      (GelMS). Then, drug-containing GelMS were assembled on GO/Ti scaffolds and
      anchored by the functional groups of GO. The modified scaffold independently
      delivered multiple biomolecules with different physiochemical properties, without
      interfering with each other. Thus, the GO/Ti scaffold has the dual functions of
      inducing bone regeneration and preventing bacterial infection. In summary, this
      mussel-inspired GO/Ti hybrid scaffold combined the good mechanical properties of
      Ti scaffolds and the advantages of GO nanosheets. GO nanosheets with their unique
      nanostructure and functional groups, together with GelMS on Ti scaffolds, are
      suitable carriers for drug delivery and provide adhesive sites for cell adhesion
      and create nanostructured environments for bone regeneration.

PMID- 29376157
TI  - An underwater superoleophobic nanofibrous cellulosic membrane for oil/water
      separation with high separation flux and high chemical stability.
AB  - Oil spills and an increasing demand for the treatment of industrial oily
      wastewater are driving the need for continuous large-scale oil/water separation
      processes. Herein, we report a nanofibrous cellulosic membrane (NFC membrane) for
      the continuous high-flux separation of large amounts of oil/water mixtures. The
      NFC membrane was fabricated using wet electrospinning, a facile yet effective
      method for stacking nanofibrous membranes with uniform porous structures on a
      substrate. Owing to its cellulosic nature, the membrane showed excellent
      underwater superoleophobicity along with robust chemical stability and was able
      to separate oil/water mixtures at efficiencies exceeding 99%. Repetitive
      oil/water separations could be performed using a single membrane, during which
      the oil content in the filtrate remained extremely low (<29 ppm). The nanofibrous
      membrane exhibited a fine porous structure that was interconnected throughout the
      membrane, resulting in a high oil intrusion pressure (>30 kPa) that allowed not
      only gravity-driven but also pressure-driven separation of oil/water mixtures.
      The separation flux reached 120 000 L m-2 h-1 during pressure-driven separations,
      which is a very promising feature for actual applications such as the large-scale
      treatment of industrial oily wastewater.

PMID- 29376158
TI  - Light-induced cross-linking and post-cross-linking modification of polyglycidol.
AB  - The photoinduced radical generation process has received renewed interest due to
      its economic and ecological appeal. Herein the light-induced cross-linking of
      functional polyglycidol and its post-cross-linking modification are presented.
      Linear polyglycidol was first functionalized with a tertiary amine in a two-step
      reaction. Dimethylaminopropyl functional polyglycidol was cross-linked in a UV
      light mediated reaction with camphorquinone as a type II photoinitiator. The
      cross-linked polyglycidol was further functionalized by quaternization with
      various organoiodine compounds. Aqueous dispersions of the cross-linked polymers
      were investigated by means of DLS and zeta potential measurements. Polymer films
      were evaluated by DSC and XPS.

PMID- 29376159
TI  - Singlet-triplet energy gaps and the degree of diradical character in binuclear
      copper molecular magnets characterized by spin-flip density functional theory.
AB  - Molecular magnets, defined here as organic polyradicals, can be used as building
      blocks in the fabrication of novel and structurally diverse magnetic light-weight
      materials. We present a theoretical investigation of the lowest spin states of
      several binuclear copper diradicals. In contrast to previous studies, we consider
      not only the energetics of the low-lying states (which are related to the
      exchange-coupling parameter within the Heisenberg-Dirac-van-Vleck model), but
      also the character of the diradical states themselves. We use natural orbitals,
      their occupations, and the number of effectively unpaired electrons to quantify
      bonding patterns in these systems. We compare the performance of spin-flip time
      dependent density functional theory (SF-TDDFT) using various functionals and
      effective core potentials against the wave function based approach, equation-of
      motion spin-flip coupled-cluster method with single and double substitutions (EOM
      SF-CCSD). We find that SF-TDDFT paired with the PBE50 and B5050LYP functionals
      performs comparably to EOM-SF-CCSD, with respect to both singlet-triplet gaps and
      states' characters. Visualization of frontier natural orbitals shows that the
      unpaired electrons are localized on copper centers, in some cases exhibiting
      slight through-bond interaction via copper d-orbitals and p-orbitals of
      neighboring ligand atoms. The analysis reveals considerable interactions between
      the formally unpaired electrons in the antiferromagnetic diradicaloids, meaning
      that they are poorly described by the Heisenberg-Dirac-van-Vleck model. Thus, for
      these systems the experimentally derived exchange-coupling parameters are not
      directly comparable with the singlet-triplet gaps. This explains systematic
      discrepancies between the computed singlet-triplet energy gaps and the exchange
      coupling parameters extracted from experiment.

PMID- 29376160
TI  - Anomalous thermoelectricity of pure ZnO from 3D continuous ultrathin nanoshell
      structures.
AB  - ZnO is a potential thermoelectric material because of its non-toxicity, high
      thermal stability, and relatively high Seebeck coefficient (S) of metal oxides.
      However, the extremely low figure of merit (zT), which comes from a high thermal
      conductivity (kappa) over 40 W m-1 K-1, limits the thermoelectric application of
      ZnO. In particular, below 500 K, ZnO exhibits a nearly negligible zT (<10-3),
      unless a dopant is incorporated into the crystal structure. Here, we propose a
      new strategy for achieving a reduced kappa and a correspondingly increased zT of
      pure ZnO over a wide temperature range from 333 K to 723 K by forming an ~72 nm
      thick, 3D continuous ultrathin nanoshell structure. The suppressed kappa of the
      3D ZnO film is ~3.6 W m-1 K-1 at 333 K, which is ~38 times lower than that of the
      blanket ZnO film (3.2 MUm thick), which was set as a reference. The experimental
      zT of the 3D ZnO film is ~0.017 at 333 K, which is the highest value among pure
      ZnO reported to date and is estimated to increase by ~0.072 at 693 K according to
      the Debye-Callaway approach. Large-area (~1 in2) fabrication of the 3D ZnO film
      with high structural uniformity allows the realization of an integrated
      thermoelectric device, which generates ~60 mV at a temperature difference of 40 K
      along the in-plane direction.

PMID- 29376161
TI  - Dialumination of unsaturated species with a reactive bis(cyclopentadienyl)
      dialane.
AB  - A new bis(cyclopentadienyl) dialane is prepared, which shows controlled,
      selective dialumination reactions with a conventional alkyne, an electron-rich
      alkyne, and an azide. The reactions provide structurally diverse products,
      featuring a range of aluminium coordination numbers, cyclopentadienyl binding
      modes, and cyclic motifs. The variable nature of the bonding in the Cp*Al units
      allows a range of binding modes depending on the electronic requirements of the
      Al atom and provides new possibilities to the chemistry of dialanes, as
      demonstrated by the isolation of a double internal Lewis adduct with "ring
      slipped" Cp* rings in this work.

PMID- 29376162
TI  - Plasmonic metal-semiconductor photocatalysts and photoelectrochemical cells: a
      review.
AB  - The incorporation of plasmonic metals into semiconductors is a promising route to
      improve the performance of photocatalysts and photoelectrochemical cells. This
      article summarizes the three major mechanisms of plasmonic energy transfer from a
      metal to a semiconductor, including light scattering/trapping, plasmon-induced
      resonance energy transfer (PIRET) and hot electron injection (also called direct
      electron transfer (DET)). It also discusses the rational design of plasmonic
      metal-semiconductor heterojunctions based on the underlying plasmonic energy
      transfer mechanisms. Moreover, this article highlights the applications of
      plasmonic photocatalysts and photoelectrochemical cells in solar water splitting,
      carbon dioxide reduction and environmental pollutant decomposition.

PMID- 29376163
TI  - Delivery systems for agriculture: Fe-EDDHSA/CaCO3 hybrid crystals as adjuvants
      for prevention of iron chlorosis.
AB  - Fe-EDDHSA/CaCO3 hybrid crystals are synthesized and tested in vitro to determine
      their effect in treating iron chlorosis in kiwifruit plants, used as a proof of
      concept. Under the alkaline conditions provided by the calcareous substrate,
      plants release protons that dissolve the hybrids and trigger Fe uptake. These
      CaCO3 hybrids represent a new system for active molecule delivery in agriculture.

PMID- 29376164
TI  - Effect of hydrogenation on the structure and magnetic properties of an iron oxide
      cluster.
AB  - The structure and properties of the Fe8O12Hn clusters (n = 0-18) are computed
      using the all-electron density functional theory with the generalized gradient
      approximation for the exchange-correlation potential. The ground state of Fe8O12
      is found to be a singlet state having a bi-capped octahedron geometry. Upon
      hydrogenation, the octahedral framework of Fe is retained in Fe8O12Hn up to n <
      7, beyond which point the iron octahedron transforms into a cube. Hydrogen atoms
      are bound to oxygen atoms up to n = 12, but they bind to the faces of the Fe8
      cube when n > 12. The total spin magnetic moment of a Fe8O12Hn cluster is larger
      than 6 MUB for 1 <= n <= 18, except for n = 8 and 10, where the lowest total
      energy states are antiferromagnetic singlets. The reason for this deviation from
      the general behavior in the Fe8O12Hn series is attributed to the collective
      superexchange phenomenon. Surprisingly, the total spin magnetic moment of a
      Fe8O12Hn cluster is found to be substantially larger than the total spin magnetic
      moment of the bare Fe8 cluster when n = 12-18. All of the Fe8O12Hn clusters are
      stable with respect to an abstraction of a single hydrogen atom but are unstable
      toward the abstraction of an H2 dimer when n =10 and n = 14-18.

PMID- 29376165
TI  - Cobalt-to-vanadium charge transfer in polyoxometalate water oxidation catalysts
      revealed by 2p3d resonant inelastic X-ray scattering.
AB  - Two isostructural cobalt containing polyoxometalate water oxidation catalysts,
      [Co4(H2O)2(alpha-PW9O34)2]10- (Co4P2) and [Co4(H2O)2(alpha-VW9O34)2]10- (Co4V2),
      exhibit large differences in their catalytic performance. The substitution of
      phosphorus centers in Co4P2 with redox-active vanadium centers in Co4V2 leads to
      electronic structure modifications. Evidence for the significance of the vanadium
      centers to catalysis, predicted by theory, was found from soft X-ray absorption
      (XAS) and resonant inelastic X-ray scattering (RIXS). The XAS and RIXS spectra
      determine the electronic structure of the cobalt and vanadium sites in the pre
      reaction state of both Co4V2 and Co4P2. High-energy resolution RIXS results
      reveal that Co4V2 possesses a smaller ligand field within the tetra-cobalt core
      and a cobalt-to-vanadium charge transfer band. The differences in electronic
      structures offer insights into the enhanced catalysis of Co4V2.

PMID- 29376166
TI  - Bacterial growth sensing in microgels using pH-dependent fluorescence emission.
AB  - We report the development of a platform for sensing bacterial growth by observing
      pH change via a change in fluorescence. While the platform allows for the rapid
      detection of bacteria it is sensitive enough to detect even ~104 CFU of bacteria.
      The platform can differentiate between resistant and non-resistant strains of E.
      coli in ~4 to 6 hours, which is better than currently used clinical methods.

PMID- 29376167
TI  - Nonequilibrium self-assembly induced Liesegang rings in a non-isothermal system.
AB  - We propose a model to show the formation of Liesegang rings under non-isothermal
      conditions. The model formulates reaction-diffusion equations for all components
      intervening in the process together with an evolution equation for the
      temperature. The reactive parts in these equations follow from the analysis of
      the non-equilibrium self-assembly (NESA) process undergone by the meso-particles
      which make up the patterns. The solution of these equations enables us to know
      the concentration of each component, the spherical structures diameter, and the
      system temperature as a function of time and radial position. The values found
      for the structures diameter and the rings position are in agreement with the
      experiments. The results for the system temperature with peaks at the rings
      positions suggest that heat accumulates at these positions as a consequence of
      the dissipation inherent to the NESA process. Our model enables us to rationalize
      how from non-homogeneous initial conditions a transient self-organization process
      involving formation of self-assembled structures may produce macroscopic
      patterns. It can, in general, be used to analyze pattern formation due to
      diffusion-reaction-precipitation processes with potential applications in the
      design of advanced materials.

PMID- 29376168
TI  - Mercury methylation in stormwater retention ponds at different stages in the
      management lifecycle.
AB  - Stormwater retention ponds effectively manage erosion, flooding, and pollutant
      loadings, but are also sources of methylmercury (MeHg), a bioaccumulative
      neurotoxin which is produced by anaerobic aquatic microorganisms. Stormwater
      retention ponds have a 10-15 year working life, after which they are dredged and
      reflooded. In this study, we related MeHg biogeochemistry to the different stages
      of the management lifecycle. In a new, a dredged, and a mature stormwater
      retention pond, we measured MeHg and inorganic mercury (IHg) concentrations, and
      the potential for MeHg formation (Kmeth), during the early summer, peak summer,
      and fall of 2013. In our study sites, MeHg concentrations appear to be driven by
      mercury (Hg) methylation, indicated by significant correlations between Kmeth
      values and MeHg concentrations and the percent of Hg present as MeHg.
      Relationships between Hg variables and ancillary biogeochemistry suggest that Hg
      methylation is carried out by sulfate reducing bacteria, but that the process is
      modulated by the supply of IHg substrate, sediment total and labile organic
      carbon, and possibly competition with nitrate reducers. Wetlands at different
      points in the management lifecycle differ in terms of their MeHg biogeochemistry.
      The organic matter-poor new wetland had low MeHg production (mean Kmeth 0.014 per
      day) and sediment concentrations (mean 0.015 ng g-1), while the mature wetland
      both produced and accumulated MeHg about five times more actively. Methylmercury
      production capacity was only temporarily reduced in the reflooded sediments of
      the dredged wetland, which experienced rapid increases in Kmeth values from low
      (mean 0.015 per day) immediately after dredging, to values similar to those in
      the mature wetland after five months. This pattern may have been related to
      recolonization of the sediments with mercury methylators or increased microbial
      activities in response to the addition of fresh organic matter. Additional
      studies should focus on the applicability of these patterns to stormwater
      retention ponds in other areas, and particularly investigate the effects of
      stormwater pond dredging on their microbial ecology and MeHg biogeochemistry.

PMID- 29376169
TI  - Kinetics of autoignition: a simple intuitive interpretation and its relation to
      the Livengood-Wu integral.
AB  - It is well known that the gas-phase autoignition phenomenon often involves
      branched chain reactions as well as the acceleration of reactions by thermal
      feedback. Despite the huge combustion kinetic mechanisms of large hydrocarbons
      found in practical fuels, chain reactions in the early stages of alkane
      autoignition exhibit simple kinetics since the pseudo-first-order assumption and
      the linear approximation are valid. In this study, this simple picture of
      autoignition will be presented starting from the H2-O2 system and then extending
      to practical fuel-air mixtures. The present interpretation gives the theoretical
      rationale for the Livengood-Wu integral which is known as an empirical method to
      predict the timing of knock in spark-ignition engines.

PMID- 29376170
TI  - Studies towards the synthesis of Pd(ii)-containing [2] and [3]catenanes in
      aqueous media.
AB  - Here is reported the investigation of a synthetic route for the preparation of
      Pd(ii)-containing catenanes in aqueous media. A pseudorotaxane intermediate was
      prepared, which can potentially be converted into a series of catenanes. From the
      pseudorotaxane, using a Pd(ii)-driven clipping step a dinuclear [3]catenane was
      obtained in the solid state.

PMID- 29376171
TI  - New hole transporting materials for planar perovskite solar cells.
AB  - Two new hole transporting materials (HTMs) based on triphenylamine and carbazole
      core moieties are designed and applied in planar perovskite solar cells. 18.2%
      power conversion efficiency (PCE) has been achieved, and 84% of the initial
      performance can be retained after 50 days.

PMID- 29376172
TI  - Base-promoted amide synthesis from aliphatic amines and ynones as acylation
      agents through C-C bond cleavage.
AB  - A new protocol for the synthesis of amides via base-promoted cleavage of the
      C(sp)-C(CO) bond of ynones with aliphatic primary and secondary amines under
      transition-metal-, ligand-, and oxidant-free conditions has been developed. This
      method exhibits a wide substrate scope, high functional group tolerance and
      exclusive chemoselectivity, as well as mild reaction conditions.

PMID- 29376173
TI  - Enhanced planar perovskite solar cell efficiency and stability using a
      perovskite/PCBM heterojunction formed in one step.
AB  - Perovskite/PCBM heterojunctions are efficient for fabricating perovskite solar
      cells with high performance and long-term stability. In this study, an efficient
      perovskite/PCBM heterojunction was formed via conventional sequential deposition
      and one-step formation processes. Compared with conventional deposition, the one
      step process was more facile, and produced a perovskite thin film of
      substantially improved quality due to fullerene passivation. Moreover, the
      resulting perovskite/PCBM heterojunction exhibited more efficient carrier
      transfer and extraction, and reduced carrier recombination. The perovskite solar
      cell device based on one-step perovskite/PCBM heterojunction formation exhibited
      a higher maximum PCE of 17.8% compared with that from the conventional method
      (13.7%). The device also showed exceptional stability, retaining 83% of initial
      PCE after 60 days of storage under ambient conditions.

PMID- 29376174
TI  - Rock the nucleus: significantly enhanced nuclear membrane permeability and gene
      transfection by plasmonic nanobubble induced nanomechanical transduction.
AB  - Efficient delivery to the cell nucleus remains a significant challenge for many
      biomolecules, including anticancer drugs, proteins and DNAs. Despite numerous
      attempts to improve nuclear import including the use of nuclear localization
      signal (NLS) peptides and nanoparticle carriers, they are limited by the
      nanoparticle size, conjugation method, dependence on the functional nuclear
      import and intracellular trafficking mechanisms. To overcome these limitations,
      here we report that the nanomechanical force from plasmonic nanobubbles increases
      nuclear membrane permeability and promotes universal uptake of macromolecules
      into the nucleus, including macromolecules that are larger than the nuclear pore
      complex and would otherwise not enter the nucleus. Importantly, we show that
      plasmonic nanobubble-induced nanomechanical transduction significantly improves
      gene transfection and protein expression, compared to standard electroporation
      treatment alone. This novel nanomechanical transduction increases the size range
      and is broadly applicable for macromolecule delivery to the cell nucleus, leading
      to new opportunities and applications including for gene therapy and anticancer
      drug delivery.

PMID- 29376175
TI  - A novel steric effect-regulated isothermal exponential amplification technology
      for the one-step homogeneous sensing of proteins.
AB  - A simple and homogeneous technology, the steric effect-regulated isothermal
      exponential amplification reaction (SER-EXPAR), was developed to sense proteins.
      By using a small molecule linked DNA nanostructure, termed enzyme-binding hairpin
      (EBH), the protein-small molecule binding events could be readily sensed by
      utilizing the steric effect generated between the protein and enzyme. It set free
      the enzyme to be active again, thus regulating the amplification rate of EXPAR.

PMID- 29376176
TI  - A piezo-ring-on-chip microfluidic device for simple and low-cost mass
      spectrometry interfacing.
AB  - Mass spectrometry (MS) interfacing technology provides the means for
      incorporating microfluidic processing with post MS analysis. In this study, we
      propose a simple piezo-ring-on-chip microfluidic device for the controlled
      spraying of MALDI-MS targets. This device uses a low-cost, commercially-available
      ring-shaped piezoelectric acoustic atomizer (piezo-ring) directly integrated into
      a polydimethylsiloxane microfluidic device to spray the sample onto the MS target
      substrate. The piezo-ring-on-chip microfluidic device's design, fabrication, and
      actuation, and its pulsatile pumping effects were evaluated. The spraying
      performance was examined by depositing organic matrix samples onto the MS target
      substrate by using both an automatic linear motion motor, and manual deposition.
      Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) was
      performed to analyze the peptide samples on the MALDI target substrates. Using
      our technique, model peptides with 10-6 M concentration can be successfully
      detected. The results also indicate that the piezo-ring-on-chip approach forms
      finer matrix crystals and presents better MS signal uniformity with little sample
      consumption compared to the conventional pipetting method.

PMID- 29376177
TI  - Mediator- and co-catalyst-free direct Z-scheme composites of Bi2WO6-Cu3P for
      solar-water splitting.
AB  - Exploring new single, active photocatalysts for solar-water splitting is highly
      desirable to expedite current research on solar-chemical energy conversion. In
      particular, Z-scheme-based composites (ZBCs) have attracted extensive attention
      due to their unique charge transfer pathway, broader redox range, and stronger
      redox power compared to conventional heterostructures. In the present report, we
      have for the first time explored Cu3P, a new, single photocatalyst for solar
      water splitting applications. Moreover, a novel ZBC system composed of Bi2WO6
      Cu3P was designed employing a simple method of ball-milling complexation. The
      synthesized materials were examined and further investigated through various
      microscopic, spectroscopic, and surface area characterization methods, which have
      confirmed the successful hybridization between Bi2WO6 and Cu3P and the formation
      of a ZBC system that shows the ideal position of energy levels for solar-water
      splitting. Notably, the ZBC composed of Bi2WO6-Cu3P is a mediator- and co
      catalyst-free photocatalyst system. The improved photocatalytic efficiency
      obtained with this system compared to other ZBC systems assisted by mediators and
      co-catalysts establishes the critical importance of interfacial solid-solid
      contact and the well-balanced position of energy levels for solar-water
      splitting. The promising solar-water splitting under optimum composition
      conditions highlighted the relationship between effective charge separation and
      composition.

PMID- 29376178
TI  - An isolable beta-diketiminato chlorosilylene.
AB  - The first beta-diketiminate ligated chlorosilylene has been synthesised and
      isolated from the corresponding beta-diketiminato dichlorohydrosilane through
      dehydrochlorination with an N-heterocyclic carbene.

PMID- 29376179
TI  - Kinetic and thermodynamic analysis of triplex formation between peptide nucleic
      acid and double-stranded RNA.
AB  - Kinetics and thermodynamics of triplex formation between 9-mer homopyrimidine PNA
      (H2N-Lys-TCTCCTCCC-CONH2) and double-stranded RNA (dsRNA, 5'-AGAGGAGGG-3'/3'
      UCUCCUCCC-5') at acidic pH were studied by means of a stopped-flow technique and
      isothermal titration calorimetry (ITC). These results revealed the following main
      findings: (i) the stable PNA-dsRNA triplex formation mostly originated from the
      large association rate constant (kon), which was dominated by both the charge
      neutral PNA backbone and the protonation level of the PNA cytosine. (ii) The
      temperature dependence of the enthalpy change (DeltaH) and kon suggested that the
      association phase of the PNA-dsRNA triplex formation comprised a non-directional
      nucleation-zipping mechanism that was coupled with the conformational transition
      of the unbound PNA. (iii) The destabilization by a mismatch in the dsRNA sequence
      mainly resulted from the decreased magnitude of both kon and DeltaH. (iv) There
      was sequence and position dependence of the mismatch on DeltaH and the activation
      energy (Eon), which illustrated the importance of base pairing in the middle of
      the sequence. Our results for the first time revealed an association mechanism
      for the PNA-dsRNA triplex formation. A set of the kinetic and thermodynamic data
      we reported here will also expand the scope of understanding for nucleic acid
      recognition by PNA.

PMID- 29376180
TI  - H-Transfer reactions of internal alkenes with tertiary amines as H-donors on
      carbon supported noble metals.
AB  - A hydride transfer reaction with tertiary amines was observed in the presence of
      noble metals on a carbon support. Hydride transfer had been documented previously
      in terms of activated allyl-type carbon-carbon double bonds containing carbonyl
      derivatives in the presence of triethyl amine (conjugate reduction). The proposed
      mechanism is a hydride transfer reaction in which the metal serves as the
      reaction partner of the hydrido-metal iminium adduct formation. The saturation of
      a non-activated internal double bond containing compound, such as methyl oleate
      and trans-5-decene as substrates, was observed for the first time in this work.
      The pre-reduced catalyst samples showed high activity; in the presence of Pd/C,
      Pt/C and Rh/C partial to complete conversion was detected at 140  degrees C in a
      p-xylene solvent without molecular hydrogen. Higher molecular weight byproducts
      of the amines were formed, while in the case of the substrates negligible amounts
      of unreacted but double bond migrated species were present. There is a
      possibility of usage of alkyl amines other than triethylamine; thus use of
      tributyl-, tripentyl-, trihexylamine and N,N-diisopropylethylamine, as well as
      cyclic 1-ethylpyrrolidine and 1-ethylpiperidine, was investigated. Cyclic amines
      and diisopropyl derivatives as H sources produced the highest conversion, while
      amines with longer alkyl chains showed minor activity. As a clear indication of H
      donation, the formation of unsaturated amine species such as 1-ethyl-pyrrole and
      pyridine was observed.

PMID- 29376181
TI  - Supramolecular chiroptical switching of helical-sense preferences through the two
      way intramolecular transmission of a single chiral source.
AB  - We demonstrate a chiroptical switching system with a simple molecule. The
      molecule contains a pair of chromophores of diphenylacetylene that are linked
      with a diyne bond and arranged to exert exciton coupling in helically folded
      forms with (M)- or (P)-helicity. A tertiary amide group is attached to each end
      of the looped molecule. The amide carbonyls were used to capture a ditopic
      hydrogen-bonding guest. A chiral auxiliary group on the amide nitrogen acted as a
      chiral handle to control the helical-sense preference of dynamic helical forms of
      the loop. The helical-sense preference is brought about by an intramolecular
      transmission of point chirality associated with the loop. The preferred sense was
      switched upon complexation with an achiral additive through the formation of
      hydrogen bonds. In both states, before and after complexation, the helical-sense
      preferences were controlled through two-way transmission of the single chiral
      source.

PMID- 29376182
TI  - Tunable seat belt behavior in nanocomposite interfaces inspired from bacterial
      adhesion pili.
AB  - A challenging problem in designing nanocomposites is to engineer nanoparticle
      interfaces that have tunable cohesive strength and rate-responsive behavior, for
      which inspiration can be taken from biological systems. An exemplary bio
      interface is the Chaperone-Usher (CU) pili, such as type 1 expressed by bacteria
      Escherichia coli. The pili have unique biomechanical properties that enhance the
      ability of bacteria to sustain attachment to surfaces under large stresses, such
      as constant force extensibility, logarithmic velocity-uncoiling force dependence,
      and adhesive tips with catch bond behavior that exhibit longer bond life-times at
      greater force levels. Although biophysics of the pili under strain or stress is
      well-studied for anti-infective applications that aim to compromise pili
      adhesion, utilizing the biomechanical properties of the pili in material design
      applications is yet to be explored. In this work, we modeled the elongation of a
      single CU pilus with catch bond tip adhesin and examined its toughness response
      using Monte Carlo simulations. We showed that the pilus can act as a "molecular
      seat belt" that exhibits low toughness when pulled slowly and high toughness when
      pulled rapidly. Furthermore, we found that systematically varying the catch bond
      and shaft parameters leads to tunable seat belt behavior at the interface, where
      the sharpness of the transition from the low toughness to the high toughness
      regime and the velocity at the start of the transition can be dictated by
      molecular design parameters. Lastly, we tested the performance of CU pilus in
      slowing down a fast particle, and reveal that pili can effectively stop micron
      size projectiles with high initial velocities. The molecular seat belt mechanism
      presented here provides insight into how nanocomposite interfaces can be
      engineered to create molecular networks with linkers that switch on or off
      depending on strain rate.

PMID- 29376183
TI  - Comment on: Definitive tests for dengue fever: when and which should I use?

PMID- 29376184
TI  - Authors' reply.

PMID- 29376185
TI  - Internationalising Singapore Medicine.

PMID- 29376186
TI  - Ministry of Health Clinical Practice Guidelines: Hypertension.
AB  - The Ministry of Health (MOH) has updated the clinical practice guidelines on
      hypertension to provide doctors and patients in Singapore with evidence-based
      treatment for hypertension. This article reproduces the introduction and
      executive summary (with recommendations from the guidelines) from the MOH
      clinical practice guidelines on hypertension, for the information of SMJ readers.
      Chapters and page numbers mentioned in the reproduced extract refer to the full
      text of the guidelines, which are available from the Ministry of Health website:
      http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guideline
      /cpg_medical.html. The recommendations should be used with reference to the full
      text of the guidelines. Following this article are multiple choice questions
      based on the full text of the guidelines.

PMID- 29376187
TI  - Severo Ochoa (1905-1993): The man behind RNA.

PMID- 29376188
TI  - Fall concern about older persons shifts to carers as changing health policy
      focuses on family, home-based care.
AB  - With the Singaporean population ageing at an exponential rate, home carers are
      increasingly becoming essential partners in fall prevention and care delivery for
      older persons living at home and in the community. Singapore, like other Asian
      countries, regards the family as the main support structure for the older person,
      and national policies have been implemented to support this cultural expectation.
      Family carers experience similar concerns as older persons with regard to fall
      risk, and identifying and addressing these concerns can potentially lower fall
      risk and improve fall prevention for older persons. It is timely to remind
      ourselves - as concern about falls in older persons begins to shift to carers -
      to incorporate the influence of Asian cultural values and unique family dynamics
      of outsourcing family caregiving, in the management of older persons' fall risk
      in the community.

PMID- 29376189
TI  - Clinics in diagnostic imaging (183).
AB  - Hydrocoele of the canal of Nuck is a rare condition in adult women caused by a
      failure of complete obliteration of the canal of Nuck. It may be likened to a
      patent processus vaginalis in men. In most cases, the diagnosis is made during
      surgery as it is often mistaken for an inguinal hernia. We report a case where
      the diagnosis of this condition was made preoperatively on imaging. The salient
      anatomy, clinical features, radiological images and surgical management are
      discussed and the medical literature reviewed.

PMID- 29376190
TI  - A time for reflection and thanks.

PMID- 29376191
TI  - New Editor-in-Chief-welcome to Simon Boulton!

PMID- 29376192
TI  - Modifications of the 26S proteasome during boar sperm capacitation.
AB  - Protein ubiquitination is a stable, reversible post-translational modification,
      targeting proteins for degradation/recycling by the 26S proteasome in a well
      characterized enzymatic cascade. Studies have revealed the role of UPS in the
      regulation of fertilization, including sperm-zona pellucida interactions and the
      early event of sperm capacitation. The present study investigates the changes in
      proteasome compartmentalization, subunit composition and post-translational
      modifications during in vitro capacitation of fresh boar spermatozoa. We observed
      capacitation-dependent shedding of both 20S core and 19S regulatory particles
      from the acrosome that was associated with decreased plasma membrane integrity,
      independent of proteasomal inhibition. Subunits PSMA1-7 of the 20S core did not
      appear to undergo post-translational modifications during capacitation, based on
      invariant molecular masses before and after capacitation; however, we observed
      multiple PSMD4 forms of 19S regulatory particles (50, 53, 70, 115-140, 160 and
      >176 kDa) sequentially released from spermatozoa. PSMD4 subunit was found to be
      post-translationally modified during the course of capacitation, resulting in
      changes of apparent molecular mass, some of which were dependent on proteasomal
      inhibition. These results show that the sperm proteasomes are being modified
      during sperm capacitation. Additional studies of individual 26S proteasome
      subunits will be required to elucidate these modifications and to understand how
      UPS modulates sperm capacitation.

PMID- 29376193
TI  - Portable low-power thermal cycler with dual thin-film Pt heaters for a polymeric
      PCR chip.
AB  - Polymerase chain reaction (PCR) has been widely used for major definite
      diagnostic tool, but very limited its place used only indoor such as hospital or
      diagnosis lab. For the rapid on-site detection of pathogen in an outdoor
      environment, a low-power cordless polymerase chain reaction (PCR) thermal cycler
      is crucial module. At this point of view, we proposed a low-power PCR thermal
      cycler that could be operated in an outdoor anywhere. The disposable PCR chip was
      made of a polymeric (PI/PET) film to reduce the thermal mass. A dual arrangement
      of the Pt heaters, which were positioned on the top and bottom of the PCR chip,
      improved the temperature uniformity. The temperature sensor, which was made of
      the same material as the heater, utilized the temperature dependence of the Pt
      resistor to ensure simple fabrication of the temperature sensor. Cooling the PCR
      chip using dual blower fans enabled thermal cycling to operate with a lower power
      than that of a Peltier element with a high power consumption. The PCR components
      were electrically connected to a control module that could be operated with a Li
      ion battery (12 V), and the PCR conditions (temperature, time, cycle, etc.) were
      inputted on a touch screen. For 30 PCR cycles, the accumulated power consumption
      of heating and cooling was 7.3 Wh, which is easily available from a compact
      battery. Escherichia coli genomic DNA (510 bp) was amplified using the proposed
      PCR thermal cycler and the disposable PCR chip. A similar DNA amplification
      capability was confirmed using the proposed portable and low-power thermal cycler
      compared with a conventional thermal cycler.

PMID- 29376195
TI  - Efficacy, safety and outcome of frameless image-guided robotic radiosurgery for
      brain metastases after whole brain radiotherapy.
AB  - Estimating efficacy, safety and outcome of frameless image-guided robotic
      radiosurgery for the treatment of recurrent brain metastases after whole brain
      radiotherapy (WBRT). We performed a retrospective single-center analysis
      including patients with recurrent brain metastases after WBRT, who have been
      treated with single session radiosurgery, using the CyberKnife(r) Radiosurgery
      System (CKRS) (Accuray Inc., CA) between 2011 and 2016. The primary end point was
      local tumor control, whereas secondary end points were distant tumor control,
      treatment-related toxicity and overall survival. 36 patients with 140 recurrent
      brain metastases underwent 46 single session CKRS treatments. Twenty one patients
      had multiple brain metastases (58%). The mean interval between WBRT and CKRS
      accounted for 2 years (range 0.2-7 years). The median number of treated
      metastases per treatment session was five (range 1-12) with a tumor volume of
      1.26 ccm (mean) and a median tumor dose of 18 Gy prescribed to the 70% isodose
      line. Two patients experienced local tumor recurrence within the 1st year after
      treatment and 13 patients (36%) developed novel brain metastases. Nine of these
      patients underwent additional one to three CKRS treatments. Eight patients
      (22.2%) showed treatment-related radiation reactions on MRI, three with clinical
      symptoms. Median overall survival was 19 months after CKRS. The actuarial 1-year
      local control rate was 94.2%. CKRS has proven to be locally effective and safe
      due to high local tumor control rates and low toxicity. Thus CKRS offers a
      reliable salvage treatment option for recurrent brain metastases after WBRT.

PMID- 29376194
TI  - Residual rivaroxaban exposure after discontinuation of anticoagulant therapy in
      patients undergoing cardiac catheterization.
AB  - PURPOSE: Patients treated with direct oral anticoagulants (DOACs) frequently
      undergo interventional procedures requiring temporary discontinuation of
      anticoagulant therapy. Little is known about remaining peri-procedural exposure
      to rivaroxaban in real-world patients. METHODS: Fifty-six patients with
      rivaroxaban treatment and scheduled cardiac catheterization were included in this
      prospective, observational, and single-center study. Rivaroxaban concentrations
      were determined by LC-MS/MS and a chromogenic anti-Xa assay. Population
      pharmacokinetic modeling was carried out on LC-MS/MS concentration data using
      NONMEM software, and results were applied to Monte Carlo simulations to predict
      appropriate rivaroxaban discontinuation intervals. RESULTS: Rivaroxaban
      concentrations ranged from <LLOQ to 300.6 ng/ml at the time of admission to
      hospital and from <LLOQ to 55.5 ng/ml at the beginning of the procedure. Times
      since last rivaroxaban intake were (mean +/- SD) 51.0 +/- 31.7 h (admission) and
      85.5 +/- 36.8 h (start catheterization). LC-MS/MS and anti-Xa assay results were
      in good agreement (r = 0.958); however, the anti-Xa assay may underestimate low
      rivaroxaban concentrations and overestimate rivaroxaban exposure when performed
      on plasma samples contaminated with heparins. Pharmacokinetics of rivaroxaban
      were adequately described, and simulations predicted that 95% of patients will
      have rivaroxaban concentrations <= 28.4 ng/ml (15 mg dose group) and <= 31.9
      ng/ml (20 mg dose group) after 48 h of discontinuation. CONCLUSIONS: In the
      majority of patients, rivaroxaban plasma concentrations dropped below 30 ng/ml
      after 48 h of treatment discontinuation which is considered hemostatically safe
      before surgery with high bleeding risk. For accurate determination of low
      rivaroxaban concentrations, LC-MS/MS is the preferred choice.

PMID- 29376196
TI  - A sumatriptan coarse-grained model to explore different environments: interplay
      with experimental techniques.
AB  - In this work, we developed a coarse-grained model of sumatriptan suitable for
      extensive molecular dynamics simulations. First, we confirmed the interfacial
      distribution of this drug in bilayers through cryogenic transmission electron
      microscopy and small-angle X-ray scattering techniques, as was predicted by our
      previous atomistic simulations. Based on these simulations, we developed a coarse
      grained model for sumatriptan able to reproduce its overall molecular behavior,
      captured by atomistic simulations and experiments. We then tested the sumatriptan
      model in a micellar environment along with experimental characterization of
      sumatriptan-loaded micelles. The simulation results showed good agreement with
      photon correlation spectroscopy and electrophoretic mobility experiments
      performed in this work. The particle size of the obtained micelles was comparable
      with the simulated ones; meanwhile, zeta-potential results suggest adsorption of
      the drug on the micellar surface. This model is a step forward in the search for
      a suitable drug-delivery system for sumatriptan.

PMID- 29376197
TI  - Mitochondrial A3243G mutation results in corneal endothelial polymegathism.
AB  - PURPOSE: The mitochondrial DNA point mutation A3243G leads to a spectrum of
      syndromes ranging from MIDD to MELAS. Ocular manifestations include pattern
      macular dystrophy and concentric perifoveal atrophy. Given the high metabolic
      demand of corneal endothelial cells, we performed specular biomicroscopy analysis
      in patients harboring the mitochondrial DNA point mutation A3243G to assess for
      the associated presence of corneal endothelial abnormalities. METHODS: We present
      a case series with participants from two institutions. Patients diagnosed with
      macular dystrophy associated with MIDD or MELAS, and the mitochondrial DNA point
      mutation A3243G were recruited. Exclusion criteria included a prior diagnosis, or
      a positive family history, of endothelial corneal dystrophy. Slit-lamp corneal
      examination and specular biomicroscopy were performed. Corneal endothelial cell
      count, cell size and polymegathism, and central corneal thickness were assessed.
      Patients diagnosed with MIDD or MELAS based on clinical history and examination
      were genetically tested for the mitochondrial DNA point mutation A3243G using
      pyrosequencing. RESULTS: Five patients (two male and three female participants)
      from five different families, and with different ethnic backgrounds, met the
      inclusion criteria. Their ages ranged from 41 to 60 years. Corneal endothelial
      changes observed using slit-lamp examination were primarily mild to rare guttata.
      Specular biomicroscopy displayed mainly polymegathism associated with guttata.
      The average endothelial cell count was 2358 +/- 456 cells per mm2, the average
      endothelial cell size was 442 +/- 103 MUm2 and the average central corneal
      thickness (CCT) was 551 +/- 33 MUm. These values were similar to that of the
      average population. The average coefficient of variation (COV), an index of
      heterogeneity in cell size, was 42.0 +/- 4.1%. When compared to the average
      population, the average COV was significantly higher than predicted for the
      patients' age. None of the patients had signs of corneal edema. One patient had a
      pre-Descemet's opacity. CONCLUSIONS: In patients with the mitochondrial DNA point
      mutation A3243G, corneal endothelial polymegathism is present. This is mainly
      associated with mild guttata. The findings of corneal endothelial cell
      polymegathism may be a biomarker of mitochondrial disease, specifically in
      patients with the mitochondrial DNA A3243G mutation.

PMID- 29376198
TI  - Quantitative measures of gingival recession and the influence of gender, race,
      and attrition.
AB  - BACKGROUND: Gingival recession in dentitions with otherwise healthy periodontium
      is a common occurrence in adults. Recession is clinically measured using a
      periodontal probe to the nearest millimeter. The aim of this study is to
      establish quantitative measures of recession, the clinical crown height, and a
      new measure the gingival margin-papillae measurement. The latter is seen as the
      shortest apico-coronal distance measured from the depth of the gingival margin to
      a line connecting the tips of the two adjacent papillae. METHODS: Measurements on
      all teeth up to and including the first molar were performed on pretreatment
      study models of 120 adult Caucasian and African-American subjects divided into
      four groups of 30 by gender and race. RESULTS: Both the clinical crown height and
      the gingival margin-papillae measurements gave a true positive result for changes
      associated with gingival recession. Tooth wear shortens the clinical crown, and
      therefore, the measure of clinical crown height can give a false negative result
      when gingival recession is present. However, the gingival margin-papillae
      measurement was not affected by tooth wear and gave a true positive result for
      gingival recession. Tooth wear (attrition) was not associated with an increase in
      gingival recession. These measures are also useful in detecting recession prior
      to cemental exposure. Measures for recession and tooth wear were different for
      the four demographic groups studied. CONCLUSIONS: These measures can be used as
      quantitative standards in both clinical dentistry, research, and epidemiological
      studies.

PMID- 29376199
TI  - Prophylactic negative pressure wound therapy after lower extremity fracture
      surgery: a pilot study.
AB  - PURPOSE: Infectious complications following lower extremity fracture surgery are
      a major concern and account for a substantial socio-economic burden to society.
      The aim of this pilot study was to investigate the feasibility of a new portable
      single-use negative pressure wound therapy device in patients undergoing major
      foot ankle surgery. METHODS: Patients undergoing major foot ankle fracture
      surgery at a single level 1 trauma centre were eligible for this prospective case
      series. Patient characteristics were collected, as were fracture and surgical
      characteristics. Primary outcome was surgical site infection within 30 days as
      classified by the criteria from the Centers for Disease Control and Prevention.
      Patients in the prospective cohort were case-matched with a historical cohort
      from the same institution. RESULTS: Sixty patients were included. In seven
      patients, the NPWT failed and treatment was ceased. Mean age was 44 years and 85%
      was ASA 1; 43% of the patients were actively smoking. Indications for surgery
      were midfoot, calcaneal, talar, and ankle fractures. In 53 patients, four (7.5%)
      surgical site infections occurred, two superficial (3.3%) and two (3.3%) deep
      infections. For 47 patients, a match was available. The incidence of surgical
      site infection did not statistically significantly differ between the prospective
      cohort and retrospective matched cohort (4.3 versus 14.9%, p = 0.29,
      respectively). This was also the case when looking at superficial and deep
      surgical site infections separately (0 versus 8.5%, p = 0.08, and 4.3 versus
      6.4%, respectively). CONCLUSION: We have observed surgical site infections in
      7.5% of the patients with the use of prophylactic negative pressure wound
      therapy. The incidence of surgical site infections was not statistically
      significantly lower compared to a matched historical cohort.

PMID- 29376200
TI  - Intrinsic, stimulus-driven and task-dependent connectivity in human auditory
      cortex.
AB  - A hierarchical and modular organization is a central hypothesis in the current
      primate model of auditory cortex (AC) but lacks validation in humans. Here we
      investigated whether fMRI connectivity at rest and during active tasks is
      informative of the functional organization of human AC. Identical pitch-varying
      sounds were presented during a visual discrimination (i.e. no directed auditory
      attention), pitch discrimination, and two versions of pitch n-back memory tasks.
      Analysis based on fMRI connectivity at rest revealed a network structure
      consisting of six modules in supratemporal plane (STP), temporal lobe, and
      inferior parietal lobule (IPL) in both hemispheres. In line with the primate
      model, in which higher-order regions have more longer-range connections than
      primary regions, areas encircling the STP module showed the highest inter-modular
      connectivity. Multivariate pattern analysis indicated significant connectivity
      differences between the visual task and rest (driven by the presentation of
      sounds during the visual task), between auditory and visual tasks, and between
      pitch discrimination and pitch n-back tasks. Further analyses showed that these
      differences were particularly due to connectivity modulations between the STP and
      IPL modules. While the results are generally in line with the primate model, they
      highlight the important role of human IPL during the processing of both task
      irrelevant and task-relevant auditory information. Importantly, the present study
      shows that fMRI connectivity at rest, during presentation of sounds, and during
      active listening provides novel information about the functional organization of
      human AC.

PMID- 29376201
TI  - Diagnostic Value of Circulating Free DNA Integrity and Global Methylation Status
      in Gall Bladder Carcinoma.
AB  - The current study investigates the role of circulating free DNA (cfDNA) as a
      liquid biopsy in diagnosis gall bladder carcinoma (GBC) utilizing levels of long
      DNA fragments (ALU247) derived from tumor necrosis, short apoptotic fragments
      (ALU115) denoting total cfDNA and cfDNA integrity denoting ratio of ALU247 and
      ALU115. The global methylation status of cfDNA was also estimated with the
      hypothesis that these parameters provide a diagnostic distinction between cancer
      and non-cancer subjects, with higher or altered values favoring presence of
      malignancy. Study group included 60 cases of GBC and 36 controls including
      diseased controls (cholecystitis) and healthy subjects. Median levels of ALU115,
      ALU247 and cfDNA integrity were significantly different in GBC at 1790.88,
      673.75, 0.4718 vs. controls at 840.73, 165.03, 0.1989 ng/ml respectively. Global
      DNA methylation was not significantly different between GBC at 0.679% and
      controls at 0.695%. The sensitivity and specificity of ALU 247 in discriminating
      GBC from controls was highest with a sensitivity, specificity and diagnostic
      accuracy of 80.0%, 86.1% and 82.2% respectively. Global DNA methylation showed
      lowest sensitivity of 55.0% and specificity of 50.0%. Clinico-pathological
      parameters showing significant association with cfDNA integrity, on ROC curve
      analysis, showed significant diagnostic discrimination of the tumor stage,
      lymphovascular invasion, disease stage and grade histology. This is a first time
      analysis of ALU115, ALU247 and cfDNA integrity in the diagnosis of GBC and
      confirms that the combination of ALU247 and cfDNA integrity provides good
      sensitivity, specificity and diagnostic accuracy in discriminating GBC from
      controls as well correlates with aggressive disease parameters.

PMID- 29376202
TI  - ABSI (A Body Shape Index) and ARI (Anthropometric Risk Indicator) in Bariatric
      Surgery. First Application on a Bariatric Cohort and Possible Clinical Use.
AB  - BACKGROUND: BMI (body mass index) is used to identify candidates for bariatric
      surgery, with a criterion of BMI >= 40. For lesser degrees of obesity, BMI 35
      39.9, comorbidities are also considered. A Body Shape Index (ABSI) was derived to
      correct WC (waist circumference) for BMI and height. ABSI has been shown to be a
      linear predictor of long-term mortality across the range of BMI. Anthropometric
      risk indicator (ARI) combines the complementary contributions of BMI and ABSI and
      further improves mortality hazard prediction. We report for the first time ABSI
      and ARI for a bariatric surgical cohort at baseline and with 3-year follow-up.
      METHODS: ABSI and BMI were calculated for 101 subjects from our bariatric surgery
      center database at baseline and after 3 years of follow-up. Raw values for BMI
      and ABSI were converted to Z scores and ARI values based on sex- and age-specific
      normals and risk associations from the National Health and Nutrition Examination
      Survey (NHANES) III sample of the US general population. RESULTS: Baseline scores
      for the anthropometric variables BMI and ABSI and the corresponding ARI were all
      higher than for the NHANES population sample. At 3-year post surgery, all three
      measures decreased significantly. While baseline BMI did not predict the change
      in mortality risk by ARI, baseline ABSI did (r = - 0.73), as did baseline ARI (r
      = - 0.94). CONCLUSION: Sleeve gastrectomy lowers ABSI and the associated
      mortality risk estimated from population studies after 3 years of follow-up.
      Considering our results, bariatric surgical candidates with BMI in the range of
      35 to 39.9 with an increased ABSI-related mortality risk may have considerable
      survival benefit from bariatric surgery, even in the absence of qualifying
      comorbidities. TRIAL REGISTRATION NUMBER: 2814.

PMID- 29376203
TI  - pH-Dependent Effects of L-Cysteine on Mercury Dissolution of alpha-HgS and beta
      HgS.
AB  - Mercury sulfide is an insoluble inorganic mercury compound, and it is the main
      chemical form in traditional oral mercury-containing medicines. Hg2+ has a high
      affinity for thiols, and small molecule thiols in the gastrointestinal tract may
      promote mercury dissolution of mercury sulfide by binding to Hg2+. L-cysteine is
      the only amino acid that possesses a reducing sulfhydryl group (-SH), out of the
      20 amino acids. This study investigates the effect of L-cysteine on mercury
      dissolution of mercury sulfide at pHs ranging from 1.2 to 7.2. The results showed
      that L-cysteine had different pH-dependent effects on the mercury dissolution of
      alpha-HgS and beta-HgS. For alpha-HgS, the dissolved mercury concentration
      increased from 5.47 +/- 0.97 ng/mL to 12.49 +/- 0.54 ng/mL when the pH rose from
      1.2 to 4.2, and decreased to 3.37 +/- 0.70 ng/mL at pH 6.0 and then increased to
      9.36 +/- 0.79 ng/mL at pH 7.2. For beta-HgS, the dissolved mercury concentration
      increased from 151.09 +/- 2.25 ng/mL to 2346.71 +/- 62.62 ng/mL when the pH
      increased from 1.2 to 7.2. In conclusion, L-Cys was distinctly enhanced upon
      mercury dissolution of alpha-HgS and beta-HgS with increasing pH. These results
      may contribute to our understanding of the mercury absorption mechanism of
      traditional oral mercury-containing medicines.

PMID- 29376204
TI  - The impact of gender on mortality after NSTEMI.

PMID- 29376205
TI  - Correction to: The Cancer, Educate to Prevent Model-the Potential of School
      Environment for Primary Prevention of Cancer.
AB  - The affiliation address of Dr. Helena Santos should be Faculty of Economics,
      University of Porto, Portugal and Dr. Luis Moreira's should be Research Unit in
      Education and Community Intervention - RECI & Health School of Vila Nova de Gaia 
      Piaget Institute.

PMID- 29376206
TI  - Serum adenosine deaminase activity is increased in systemic lupus erythematosus
      patients and correlated with disease activity.
AB  - Adenosine deaminase (ADA) has been found to be involved in autoimmune disease
      progression. To assess the potential application of serum ADA activity in
      diagnosing systemic lupus erythematosus (SLE) and evaluating SLE disease
      activity, we investigated the serum ADA activity of 120 SLE patients and 120
      healthy controls in the present study. The results showed that serum ADA activity
      in SLE patients was significantly increased (median (IQR) = 14 (11-19) U/L)
      compared with that in healthy controls (median (IQR) = 8 (7-10) U/L). Based on a
      receiver operating characteristic curve analysis, the optimal cut-off value for
      using serum ADA activity to diagnose SLE patients was 10.5 U/L (specificity,
      84.2%; sensitivity, 78.3%). The diagnostic performance of serum ADA activity for
      SLE patients was better than that of other conventional haematology markers.
      Moreover, serum ADA activity displayed an increasing trend with increasing SLE
      disease activity. Spearman's correlation analysis showed that serum ADA activity
      was positively correlated with SLE disease activity. These findings suggest that
      serum ADA activity could be a diagnostic marker for SLE; moreover, measuring
      serum ADA activity may be helpful for evaluating and monitoring the disease
      activity of SLE patients.

PMID- 29376207
TI  - The Prognostic Implications of FIX and FLO Patterns in Mucinous Colon Carcinomas.
AB  - PURPOSE: Colon mucinous carcinomas (MUCs) have two morphological patterns: (i)
      glands lined by mucinous epithelium with direct contact to the stroma (FIX) and
      (ii) carcinoma cells floating in mucin (FLO). In this study, we evaluated the
      prognostic value of these patterns. METHODS: Digital images were captured from
      the 38 MUC's tissue sections. A grid with 140 points was laid over the computer
      screen. Totally, 100 points, falling on tumor cells floating in mucin (FLO
      patterned cells) or on cells contacting stroma (FIX patterned cells), were
      counted. Tumors were grouped according to the median value of the FIX patterned
      cells. Cases with more than this value were grouped as FIX and less were grouped
      as FLO cases. The prognostic value of FIX and FLO pattern was evaluated. RESULTS:
      The median for FIX patterned cells was 66%, and the cases with lower values than
      this were grouped as FLO (N = 18; 47.37%), while the rest were grouped as FIX
      cases. There was no significant difference between FIX and FLO cases for overall
      survival cases (p = 0.167). For FIX cases, 62.7 and 51.3% of the patients were
      alive at second and third years, while this was 78.9 and 72.4% for the FLO group,
      respectively. CONCLUSIONS: This is the first study using a quantitative
      methodology depending on count pointing to evaluate FIX/FLO feature of MUCs to
      the best of our knowledge, although we could not observed any prognostic and
      clinicopathologic relationship statistically. This distinctive feature should be
      studied in larger cohorts with prognostic information, with a quantitative
      method, like the one that was applied in this study, in order to achieve strict
      conclusions.

PMID- 29376208
TI  - Halomonas tabrizica sp. nov., a novel moderately halophilic bacterium isolated
      from Urmia Lake in Iran.
AB  - A novel moderately halophilic, Gram-stain negative and aerobic bacterium,
      designated strain TBZ21T, was isolated from a water sample of Urmia Lake, Iran.
      Cells were observed to be non-motile rods with no flagellum, showing positive
      catalase and oxidase reactions. Strain TBZ21T was found to grow at 10-40  degrees
      C (optimum, 30  degrees C), at pH 7-10 (optimum, pH 8) and in the presence of 1
      22% (optimum, 10%). The major fatty acids were identified as C19:0 cyclo omega8c,
      C16:0, Summed features 3 (C13:0 3-OH and/or iso-C15:1 H) and 8 (C18:1 omega7c
      and/or C18:1 omega6c) and C12:0 3-OH. The major polar lipids were identified as
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an
      unidentified phosphoaminolipid. The genomic DNA G+C content of strain TBZ21T was
      determined to be 63.3 mol%. Phylogenetic analyses based on 16S rRNA gene
      sequences indicated that strain TBZ21T belongs to the genus Halomonas, and shows
      high sequence similarities to Halomonas fontilapidosi 5CRT (99.43%), Halomonas
      ventosae AL12T (98.64%), Halomonas sediminicola CPS11T (98.63%) and Halomonas
      aestuarii Hb3T (98.08%), and has low similarities (below 98.0%) with other
      members of the genus. The values of DNA-DNA relatedness between strain TBZ21T and
      the closely related strains H. fontilapidosi LMG 24455T and H. ventosae LMG
      26187T were 42 +/- 11% and 54 +/- 16%, respectively. On the basis of phenotypic,
      chemotaxonomic and molecular characteristics, strain TBZ21T is concluded to
      represent a novel species of the genus Halomonas, for which the name Halomonas
      tabrizica sp. nov. is proposed. The type strain is TBZ21T (=LMG 25445T=DSM
      23018T).

PMID- 29376210
TI  - First-in-human phase I dose escalation study of MK-8033 in patients with advanced
      solid tumors.
AB  - Background C-Met, which is frequently activated in multiple cancers, has been
      implicated in tumor formation, progression, metastasis, angiogenesis, and
      resistance to multiple therapies. MK-8033 is a small-molecule inhibitor of c-Met
      that binds preferentially to the activated conformation, and has demonstrated
      anti-tumor activity in preclinical models. This first-in-human trial was
      performed to establish the safety and maximum tolerated dose (MTD), as well as
      preliminary pharmacokinetics (PK) and clinical activity. Methods Forty-seven
      patients were enrolled in three parts. The primary objective of Parts A and B was
      safety, whereas Part C evaluated the effect of proton-pump inhibitors on MK-8033
      absorption. Dose escalation used an accelerated continual reassessment method,
      and dose-limiting toxicities (DLTs) were any treatment-related, first course non
      hematologic grade >= 3 toxicity (except alopecia or inadequately treated
      nausea/vomiting/diarrhea), grade 4 hematologic toxicity (except grade 3
      neutropenic fever and thrombocytopenia), or toxicity where treatment is held >3
      weeks. Results Forty-six patients were treated across nine dose levels, and the
      MTD was 750 mg twice daily. DLTs were fatigue, nausea, vomiting, transaminitis,
      and hypokalemia. Most frequent toxicities were fatigue (28.3%), nausea (21.7%),
      and alopecia (19.6%), predominately grade <= 2. One patient with endometriod
      adenocarcinoma achieved a partial response and eight had stable disease. Median
      progression-free survival (PFS) was 57 days. Strikingly, the PFS for the one
      responder was 846 days. PK results showed that proton-pump inhibitors have no
      effect on MK-8033 absorption. Conclusion MK-8033 was well tolerated with no
      significant toxicity issues, albeit with limited clinical activity.
      Unfortunately, the company decided to discontinue further clinical development of
      MK-8033.

PMID- 29376211
TI  - Membrane perforation rate in lateral maxillary sinus floor augmentation using
      conventional rotating instruments and piezoelectric device-a meta-analysis.
AB  - OBJECTIVES: Maxillary sinus augmentation (MSA) is a successful and predictable
      intervention with low complication rates. Perforations of the Schneiderian
      membrane may occur impairing the general success. The aim of this study was to
      compare the incidence of membrane perforations between conventional rotating
      instruments and piezoelectric devices in a meta-analysis. MATERIAL AND METHODS:
      An electronic research on MEDLINE and PubMed database was performed evaluating
      the literature from 1980 till 2016. Meta-analysis was performed with the studies
      matching the inclusion criteria. The incidence of perforations between
      conventional and piezo during the lateral maxillary sinus floor elevation was
      determined, and forest plots and a t test for significance analysis were
      performed. RESULTS: The search provided 377 articles of which 69 could be
      included. Selected non-randomised and non-controlled prospective and
      retrospective studies were incorporated. Conventional rotary instruments were
      associated with a perforation rate of 24%, the piezoelectric devices with 8% with
      statistically significant difference between both modalities (p < 0.05).
      CONCLUSION: Membrane perforations in MSA may be significantly reduced applying
      piezoelectrical devices for MSA.

PMID- 29376212
TI  - Foliar Terpene Chemotypes and Herbivory Determine Variation in Plant Volatile
      Emissions.
AB  - Plants that synthesize and store terpenes in specialized cells accumulate large
      concentrations of these compounds while avoiding autotoxicity. Stored terpenes
      may influence the quantity and profile of volatile compounds that are emitted
      into the environment and the subsequent role of those volatiles in mediating the
      activity of herbivores. The Australian medicinal tea tree, Melaleuca
      alternifolia, occurs as several distinct terpene chemotypes. We studied the
      profile of its terpene emissions to understand how variations in stored foliar
      terpenes influenced emissions, both constitutive and when damaged either by
      herbivores or mechanically. We found that foliar chemistry influenced differences
      in the composition of terpene emissions, but those emissions were minimal in
      intact plants. When plants were damaged by herbivores or mechanically, the
      emissions were greatly increased and the composition corresponded to the
      constitutive terpenes and the volatility of each compound, suggesting the main
      origin of emissions is the stored terpenes and not de novo biosynthesized
      volatiles. However, herbivores modified the composition of the volatile emissions
      in only one chemotype, probably due to the oxidative metabolism of 1,8-cineole by
      the beetles. We also tested whether the foliar terpene blend acted as an
      attractant for the specialized leaf beetles Paropsisterna tigrina and Faex sp.
      and a parasitoid fly, Anagonia zentae. None of these species responded to
      extracts of young leaves in an olfactometer, so we found no evidence that these
      species use plant odor cues for host location in laboratory conditions.

PMID- 29376213
TI  - Identification of the Female-Produced Sex Pheromone of an Invasive Greenhouse
      Pest, the European Pepper Moth (Duponchelia fovealis).
AB  - The European pepper moth (Duponchelia fovealis, Lepidoptera, Crambidae,
      Spilomelinae) is an invasive pest of greenhouses in many countries, causing
      serious damages to horticultural plants. Coupled gas chromatographic
      electroantennographic detection analysis of the female gland extract revealed two
      antennally active peaks. Using coupled gas chromatography-mass spectrometry (GC
      MS), one was identified as (Z)-11-hexadecenal (Z11-16:Ald); however, further
      analysis on different types of capillary columns indicated that the second active
      compound has two different isomers, (E)-13-octadecenal (E13-18:Ald) and (Z)-13
      octadecenal (Z13-18:Ald). The approximate ratio of E13-18:Ald, Z13-18:Ald and Z11
      16:Ald in the crude pheromone gland extract was 10:1:0.1, respectively. Single
      sensillum recordings showed that there was one sensory neuron that responded with
      a high amplitude spike to both E13-18:Ald and Z13-18:Ald, while another neuron
      housed in the same sensillum responded to Z11-16:Ald. Field evaluation of the
      identified compounds indicated that the E13-18:Ald was necessary to evoke the
      attraction of males; although the presence of Z13-18:Ald and Z11-16:Ald increased
      the catches in traps. The highest number of caught males was achieved when E13
      18:Ald, Z13-18:Ald and Z11-16:Ald were present in baits in the same ratio as in
      the female gland extract. This pheromone can be used in a monitoring strategy and
      could potentially lead to the development of mating disruption.

PMID- 29376214
TI  - Ecologically friendly ways to clean up oil spills in harbor water areas: crude
      oil and diesel sorption behavior of natural sorbents.
AB  - This work aimed to evaluate the sorption capacity of natural sorbents (wool,
      moss, straw, peat) and their composites during the sorption of crude oil and of
      diesel overspread on the water surface. The work presents the research results of
      the maximum sorption capacity of the sorbents/their composites using crude
      oil/diesel; the sorption capacity of the sorbents/their composites when crude
      oil/diesel is spilled on the water surface; and the research results of the
      unrealized part of the crude oil/diesel in the sorbents. The results of the
      analysis showed that all the sorbents and their composites have their selectivity
      to crude oil less than 50%. Also the results showed that the distribution of
      diesel and water in the sorbents and their composites is very different compared
      with the distribution of crude oil during the sorption analyses. In total, the
      diesel in the liquid mass absorbed by the straw and the peat amounted to 17 and
      20%, respectively. This shows that these sorbents are much more selective for
      water but not for diesel. A larger part of the diesel was in the liquid amount
      absorbed by the composites-up to 33%. Accordingly, the use of these composites in
      watery environments is much more effective than the use of individual sorbents.
      The composition of sorbents in the composite enhanced both the hydrophobic and
      the oleophilic properties; as a result, a more effective removal of the diesel
      and oil from the water surface was achieved.

PMID- 29376215
TI  - Effects of malathion and nitrate exposure on the zooplankton community in
      experimental mesocosms.
AB  - Surface waters are likely to be contaminated by both pesticides and fertilizers.
      Such contamination can result in changes in community composition if there is
      differential toxicity to individual taxa. We conducted a fully factorial mesocosm
      experiment that examined the single and interactive effects of environmentally
      realistic concentrations of nitrate and malathion on zooplankton communities and
      phytoplankton productivity. Malathion significantly decreased the abundance of
      total zooplankton, cyclopoid copepods, copepod nauplii, and Ceriodaphnia, and
      increased the abundance of rotifers. Nitrate addition generally had no effect on
      zooplankton; however, Ceriodaphnia abundance was higher in control mesocosms than
      in nitrate-treated mesocosms. There was only one significant interaction between
      malathion and nitrate treatments: For Ceriodaphnia, the no malathion, no nitrate
      mesocosms had much higher abundances than all other combinations of treatments.
      Without nitrate addition, chl a levels were uniformly low across all malathion
      treatments, whereas in the presence of nitrate, there were differences among the
      malathion treatments. In conclusion, our results demonstrate that malathion
      contamination of aquatic ecosystems can result in changes in the abundance and
      composition of zooplankton communities. In contrast, nitrate contamination
      appeared to have much less potential impact on zooplankton communities, either on
      its own or in interaction with malathion. Our results reinforce the notion that
      the effects of contaminants on aquatic ecosystems can be complex and further
      research examining the single and interactive effects of chemical stressors is
      needed to more fully understand their effects.

PMID- 29376216
TI  - Pollution characteristics of surface runoff under different restoration types in
      manganese tailing wasteland.
AB  - A great deal of manganese and associated heavy metals (such as Ni, Cu, Zn, Cd,
      Pb, etc.) was produced in manganese mining, smelting, and other processes and
      weathering and leaching of waste slag, which entered rainwater runoff by
      different means under the action of rainfall runoff. It caused heavy metal
      pollution in water environment to surrounding areas, and then environmental and
      human health risks were becoming increasingly serious. In the Xiangtan manganese
      mine, we studied the characteristics of nutritional pollutants and heavy metals
      by using the method of bounded runoff plots on the manganese tailing wasteland
      after carrying out some site treatments using three different approaches, such as
      (1) exposed tailings, the control treatment (ET), (2) external-soil amelioration
      and colonization of Cynodon dactylon (Linn.) Pers. turf (EC), and (3) external
      soil amelioration and seedling seeding propagation of Cynodon dactylon (Linn.)
      Pers. (ES). The research showed that the maximum runoff occurred in 20,140,712
      rainfall events, and the basic law of runoff was EC area > ET area > ES area in
      the same rainfall event. The concentration of total suspended solids (TSS) and
      chemical oxygen demand (COD) of three ecological restoration areas adopted the
      following rule: ET area > EC area > ES area. Nitrogen (N) existed mainly in the
      form of water soluble while phosphorus (P) was particulate. The highest
      concentrations of total nitrogen (TN) and total phosphorus (TP) were 11.57 +/-
      2.99 mg/L in the EC area and 1.42 +/- 0.56 mg/L in the ET area, respectively. Cr,
      Ni, Pb, Zn, Mn, and Cu in surface runoff from three restoration types all
      exceeded the class V level of the environmental quality standard for surface
      water except Cu in EC and ES areas. Pollution levels of heavy metals in surface
      runoff from three restoration areas are shown as follows: ET area > EC area > ES
      area. There was a significant positive correlation between TSS and runoff, COD,
      and TP. And this correlation was significant between total dissolved nitrogen
      (TDN), TN, total dissolved phosphorus (TDP), and TP. The six heavy metals (Cu,
      Ni, Pb, Zn, Mn, and Cr) in surface runoff of different ecological restoration
      areas were strongly related to each other, and were significantly related to the
      TSS.

PMID- 29376217
TI  - The thermal conductivity of cortical and cancellous bone.
AB  - Surgical interventions close to vulnerable structures, such as nerves, require
      precise handling of surgical instruments and tools. These tools not only pose the
      risk of mechanical damage to soft tissues, but they also generate heat, which can
      lead to thermal necrosis of bone or soft tissues. Researchers and engineers are
      trying to improve those tools through experimentation and simulations. To
      simulate temperature distributions in anatomical structures, reliable material
      constants are needed. Therefore, this study aimed at investigating the thermal
      conductivity of cortical and cancellous bone. Accordingly, a custom-made steady
      state experimental setup was designed and validated. 6 bovine and 3 human
      cortical bone samples, as well as 32 bovine cancellous bone samples, with
      variable bone volume fraction were tested. The cancellous bone samples were
      scanned by micro-computed tomography (uCT) and micro-finite element (uFE) voxel
      models were created to calculate iteratively the thermal conductivity of the bone
      marrow. The experimental results provided 0.64 +/- 0.04 W/mK for bovine cortical
      bone and 0.68 +/- 0.01 W/mK for human cortical bone. A linear dependency of
      thermal conductivity on bone volume fraction was found for cancellous bone [R
      square (R2) = 0.8096, standard error of the estimates (SEE) = 0.0355 W/mK]. The
      thermal conductivity of the bone marrow was estimated to be 0.42 +/- 0.05 W/mK.
      These results will help to improve thermal finite element simulations of the
      human skeleton and aid the development of new surgical tools or procedures.

PMID- 29376218
TI  - Early versus late ureteric stent removal after kidney transplantation.
AB  - BACKGROUND: Kidney transplantation is the treatment of choice for patients with
      end-stage kidney disease. In a previous review we concluded that the routine use
      of ureteric stents in kidney transplantation reduces the incidence of major
      urological complications (MUC). Unfortunately, this reduction appears to lead to
      a concomitant rise in urinary tract infections (UTI). For kidney recipients UTI
      is now the commonest post-transplant complication. This represents a considerable
      risk to the immunosuppressed transplant recipient, particularly in the era of
      increased immunologically challenging transplants. There are a number of
      different approaches taken when considering ureteric stenting and these are
      associated with differing degrees of morbidity and hospital cost. OBJECTIVES:
      This review aimed to look at the benefits and harms of early versus late removal
      of the ureteric stent in kidney transplant recipients. SEARCH METHODS: We
      searched the Cochrane Kidney and Transplant Specialised Register up to 27 March
      2017 through contact with the Information Specialist using search terms relevant
      to this review. Studies contained in the Specialised Register are identified
      through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE;
      handsearching conference proceedings; and searching the International Clinical
      Trials Register Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All
      RCTs and quasi-RCTs were included in our meta-analysis. We included recipients of
      kidney transplants regardless of demography (adults or children) or the type of
      stent used. DATA COLLECTION AND ANALYSIS: Two authors reviewed the identified
      studies to ascertain if they met inclusion criteria. We designated removal of a
      ureteric stent before the third postoperative week (< day 15) or during the index
      transplant admission as "early" removal. The studies were assessed for quality
      using the risk of bias tool. The primary outcome of interest was the incidence of
      MUC. Further outcomes of interest were the incidence of UTI, idiosyncratic stent
      related complications, hospital-related costs and adverse events. A subgroup
      analysis was performed examining the difference in complications reported
      depending on the type of ureteric stent used; bladder indwelling (BI) versus per
      urethral (PU). Statistical analyses were performed using the random effects model
      and results expressed as relative risk (RR) with 95% confidence intervals (CI).
      MAIN RESULTS: Five studies (1127 patients) were included in our analysis.
      Generally the risk of bias of the included studies was judged low or unclear;
      they addressed the research question and utilised a prospective randomised
      design. It is uncertain whether early stent removal verus late stent removal
      improved the incidence of MUC (5 studies, 1127 participants: RR 1.87, 95% CI 0.61
      to 5.71; I2 = 21%; low certainty evidence). The incidence of UTI may be reduced
      in the early stent removal group (5 studies, 1127 participants: RR 0.49 95% CI
      0.30 to 0.81; I2 = 59%; moderate certainty evidence). This possible reduction in
      the UTI incidence was only apparent if a BI stent was used, (3 studies, 539
      participants, RR 0.45 95% CI 0.29 to 0.70; I2 = 13%; moderate certainty
      evidence). However, if an externalised PU stent was used there was no discernible
      difference in UTI incidence between the early and late group (2 studies, 588
      participants: RR 0.60 95% CI 0.17, 2.03; I2 = 83%; low certainty evidence). Data
      on health economics and quality of life outcomes were lacking. AUTHORS'
      CONCLUSIONS: Early removal of ureteric stents following kidney transplantation
      may reduce the incidence of UTI while it uncertain if there is a higher risk of
      MUC. BI stents are the optimum method for achieving this benefit.

PMID- 29376219
TI  - Selenium for preventing cancer.
AB  - BACKGROUND: This review is the third update of the Cochrane review "Selenium for
      preventing cancer". Selenium is a naturally occurring element with both
      nutritional and toxicological properties. Higher selenium exposure and selenium
      supplements have been suggested to protect against several types of cancer.
      OBJECTIVES: To gather and present evidence needed to address two research
      questions:1. What is the aetiological relationship between selenium exposure and
      cancer risk in humans?2. Describe the efficacy of selenium supplementation for
      cancer prevention in humans. SEARCH METHODS: We updated electronic searches of
      the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2),
      MEDLINE (Ovid, 2013 to January 2017, week 4), and Embase (2013 to 2017, week 6),
      as well as searches of clinical trial registries. SELECTION CRITERIA: We included
      randomised controlled trials (RCTs) and longitudinal observational studies that
      enrolled adult participants. DATA COLLECTION AND ANALYSIS: We performed random
      effects (RE) meta-analyses when two or more RCTs were available for a specific
      outcome. We conducted RE meta-analyses when five or more observational studies
      were available for a specific outcome. We assessed risk of bias in RCTs and in
      observational studies using Cochrane's risk assessment tool and the Newcastle
      Ottawa Scale, respectively. We considered in the primary analysis data pooled
      from RCTs with low risk of bias. We assessed the certainty of evidence by using
      the GRADE approach. MAIN RESULTS: We included 83 studies in this updated review:
      two additional RCTs (10 in total) and a few additional trial reports for
      previously included studies. RCTs involved 27,232 participants allocated to
      either selenium supplements or placebo. For analyses of RCTs with low risk of
      bias, the summary risk ratio (RR) for any cancer incidence was 1.01 (95%
      confidence interval (CI) 0.93 to 1.10; 3 studies, 19,475 participants; high
      certainty evidence). The RR for estimated cancer mortality was 1.02 (95% CI 0.80
      to 1.30; 1 study, 17,444 participants). For the most frequently investigated site
      specific cancers, investigators provided little evidence of any effect of
      selenium supplementation. Two RCTs with 19,009 participants indicated that
      colorectal cancer was unaffected by selenium administration (RR 0.99, 95% CI 0.69
      to 1.43), as were non-melanoma skin cancer (RR 1.16, 95% CI 0.30 to 4.42; 2
      studies, 2027 participants), lung cancer (RR 1.16, 95% CI 0.89 to 1.50; 2
      studies, 19,009 participants), breast cancer (RR 2.04, 95% CI 0.44 to 9.55; 1
      study, 802 participants), bladder cancer (RR 1.07, 95% CI 0.76 to 1.52; 2
      studies, 19,009 participants), and prostate cancer (RR 1.01, 95% CI 0.90 to 1.14;
      4 studies, 18,942 participants). Certainty of the evidence was high for all of
      these cancer sites, except for breast cancer, which was of moderate certainty
      owing to imprecision, and non-melanoma skin cancer, which we judged as moderate
      certainty owing to high heterogeneity. RCTs with low risk of bias suggested
      increased melanoma risk.Results for most outcomes were similar when we included
      all RCTs in the meta-analysis, regardless of risk of bias. Selenium
      supplementation did not reduce overall cancer incidence (RR 0.99, 95% CI 0.86 to
      1.14; 5 studies, 21,860 participants) nor mortality (RR 0.81, 95% CI 0.49 to
      1.32; 2 studies, 18,698 participants). Summary RRs for site-specific cancers
      showed limited changes compared with estimates from high-quality studies alone,
      except for liver cancer, for which results were reversed.In the largest trial,
      the Selenium and Vitamin E Cancer Trial, selenium supplementation increased risks
      of alopecia and dermatitis, and for participants with highest background selenium
      status, supplementation also increased risk of high-grade prostate cancer. RCTs
      showed a slightly increased risk of type 2 diabetes associated with
      supplementation. A hypothesis generated by the Nutritional Prevention of Cancer
      Trial - that individuals with low blood selenium levels could reduce their risk
      of cancer (particularly prostate cancer) by increasing selenium intake - has not
      been confirmed. As RCT participants have been overwhelmingly male (88%), we could
      not assess the potential influence of sex or gender.We included 15 additional
      observational cohort studies (70 in total; over 2,360,000 participants). We found
      that lower cancer incidence (summary odds ratio (OR) 0.72, 95% CI 0.55 to 0.93; 7
      studies, 76,239 participants) and lower cancer mortality (OR 0.76, 95% CI 0.59 to
      0.97; 7 studies, 183,863 participants) were associated with the highest category
      of selenium exposure compared with the lowest. Cancer incidence was lower in men
      (OR 0.72, 95% CI 0.46 to 1.14, 4 studies, 29,365 men) than in women (OR 0.90, 95%
      CI 0.45 to 1.77, 2 studies, 18,244 women). Data show a decrease in risk of site
      specific cancers for stomach, colorectal, lung, breast, bladder, and prostate
      cancers. However, these studies have major weaknesses due to study design,
      exposure misclassification, and potential unmeasured confounding due to lifestyle
      or nutritional factors covarying with selenium exposure beyond those taken into
      account in multi-variable analyses. In addition, no evidence of a dose-response
      relation between selenium status and cancer risk emerged. Certainty of evidence
      was very low for each outcome. Some studies suggested that genetic factors might
      modify the relation between selenium and cancer risk - an issue that merits
      further investigation. AUTHORS' CONCLUSIONS: Well-designed and well-conducted
      RCTs have shown no beneficial effect of selenium supplements in reducing cancer
      risk (high certainty of evidence). Some RCTs have raised concerns by reporting a
      higher incidence of high-grade prostate cancer and type 2 diabetes in
      participants with selenium supplementation. No clear evidence of an influence of
      baseline participant selenium status on outcomes has emerged in these
      studies.Observational longitudinal studies have shown an inverse association
      between selenium exposure and risk of some cancer types, but null and direct
      relations have also been reported, and no systematic pattern suggesting dose
      response relations has emerged. These studies suffer from limitations inherent to
      the observational design, including exposure misclassification and unmeasured
      confounding.Overall, there is no evidence to suggest that increasing selenium
      intake through diet or supplementation prevents cancer in humans. However, more
      research is needed to assess whether selenium may modify the risk of cancer in
      individuals with a specific genetic background or nutritional status, and to
      investigate possible differential effects of various forms of selenium.

PMID- 29376220
TI  - Fluorescein Angiographic Abnormalities in the Contralateral Eye with Normal
      Fundus in Children with Unilateral Coats' Disease.
AB  - PURPOSE: We report the detection of peripheral retinal vascular abnormalities in
      the fellow eye with normal fundus in children with unilateral Coats' disease.
      METHODS: The clinical records of patients diagnosed with Coats' disease were
      retrospectively reviewed. We recorded the subjects' characteristics and obtained
      fundus photography and fluorescein angiography (FA) images. The main outcome
      measure was peripheral vascular abnormalities in the contralateral eye with
      normal fundus in children with unilateral Coats' disease, observed with FA.
      RESULTS: Out of 47 patients with Coats' disease, two (4.3%) were diagnosed with
      clinically bilateral Coats' disease. Of the 45 patients with presumed unilateral
      Coats' disease, four (8.9%) had bilateral abnormal peripheral vasculature in FA.
      The mean age of these four patients was 6.4 +/- 5.4 years (range, 1 to 14 years),
      and three patients were male (75%). All four had peripheral retinal nonperfusion,
      and two (50%) received laser photocoagulation due to peripheral leakage with
      telangiectatic vessels. CONCLUSIONS: Coats' disease may more often be a bilateral
      disease with asymmetry than previously thought. Patients with Coats' disease
      should undergo careful examination of the fellow eye with FA in order to detect
      and treat vascular abnormalities that are not visible clinically.

PMID- 29376221
TI  - Relationship between Pericytes and Endothelial Cells in Retinal
      Neovascularization: A Histological and Immunofluorescent Study of Retinal
      Angiogenesis.
AB  - PURPOSE: To evaluate the relationship between pericytes and endothelial cells in
      retinal neovascularization through histological and immunofluorescent studies.
      METHODS: C57BL/6J mice were exposed to hyperoxia from postnatal day (P) 7 to P12
      and were returned to room air at P12 to induce a model of oxygen-induced
      retinopathy (OIR). The cross sections of enucleated eyes were processed with
      hematoxylin and eosin. Immunofluorescent staining of pericytes, endothelial
      cells, and N-cadherin was performed. Microfluidic devices were fabricated out of
      polydimethylsiloxane using soft lithography and replica molding. Human retinal
      microvascular endothelial cells, human brain microvascular endothelial cells,
      human umbilical vein endothelial cells and human placenta pericyte were mixed and
      co-cultured. RESULTS: Unlike the three-layered vascular plexus found in retinal
      angiogenesis of a normal mouse, angiogenesis in the OIR model is identified by
      the neovascular tuft extending into the vitreous. Neovascular tufts and the three
      layered vascular plexus were both covered with pericytes in the OIR model. In
      this pathologic vascularization, N-cadherin, known to be crucial intercellular
      adhesion molecule, was also present. Further evaluation using the microfluidic in
      vitro model, successfully developed a microvascular network of endothelial cells
      covered with pericytes, mimicking normal retinal angiogenesis within 6 days.
      CONCLUSIONS: Pericytes covering endothelial cells were observed not only in
      vasculature of normal retina but also pathologic neovascularization of OIR mouse
      at P17. Factors involved in the endothelial cell-pericyte interaction can be
      evaluated as an attractive novel treatment target. These future studies can be
      performed using microfluidic systems, which can shorten the study time and
      provide three-dimensional structural evaluation.

PMID- 29376222
TI  - Comparison of the Thickness and Volume of the Macula and Fovea in Patients with
      Anisometropic Amblyopia Prior to and after Occlusion Therapy.
AB  - PURPOSE: To compare the thickness of superior, temporal, inferior, and nasal
      macula and foveal thickness and volume in patients with anisometropic amblyopia
      prior to and after successful occlusion therapy using optical coherence
      tomography (OCT) measurement. METHODS: Data were collected prospectively on 30
      patients with unilateral anisometropic amblyopia from December 2006 to August
      2007. All patients had anisometropia of 2.0 diopters or more. OCT scans were
      obtained for all patients at diagnosis. Occlusion therapy was then prescribed and
      OCT scans were obtained again at the time of successful occlusion therapy
      (defined as interocular difference of <0.1 log units). The Stratus OCT-3 was used
      to measure fovea thickness and volume and the thickness of superior, temporal,
      inferior, and nasal macula (within a diameter of 3 mm). RESULTS: Of 30 patients,
      22 (mean age of 5.8 years) had successful resolution of amblyopia. The mean
      duration of occlusion was 11.24 months and mean best-corrected visual acuity at
      diagnosis was 0.35 +/- 0.12 logarithm of the minimum angle of resolution. The
      mean thicknesses of the superior, temporal, inferior, and nasal macula prior to
      and after occlusion were not significantly different (p > 0.05). However, mean
      foveal volume prior to occlusion therapy (0.15 +/- 0.02 mm3) decreased after
      occlusion (0.14 +/- 0.01 mm3) with statistical significance (Wilcoxon signed rank
      test, p = 0.025). CONCLUSIONS: There was a meaningful decrease in foveal volume
      in patients with anisometropic amblyopia after successful occlusion therapy.
      Whether this decrease relates to visual improvement of the amblyopic eye remains
      to be determined.

PMID- 29376223
TI  - Bevacizumab versus Dexamethasone Implant Followed by Bevacizumab for the
      Treatment of Macula Edema Associated with Branch Retinal Vein Occlusion.
AB  - PURPOSE: To compare visual and anatomical outcomes of intravitreal injections of
      bevacizumab and dexamethasone implant (Ozurdex) treatment for macular edema
      associated with branch retinal vein occlusion (BRVO). METHODS: We retrospectively
      reviewed patients who underwent intravitreal bevacizumab administered monthly on
      a pro re nata (PRN) basis (26 eyes, IVB group) or an initial 700-MUg
      dexamethasone implant followed by a bevacizumab PRN injection (20 eyes, IVD
      group) for treatment of macular edema associated with BRVO. We compared best
      corrected visual acuity (BCVA) and central macular thickness (CMT). We also
      measured ellipsoid zone recovery rate and ganglion cell-inner plexiform layer
      volume within the center 6 mm zone. A linear mixed model analysis was performed
      to compare serial changes in BCVA and CMT. RESULTS: Both groups showed
      significant improvement in BCVA and significant reduction in CMT. However, BCVA
      in the first month was significantly better in the IVD group (logarithm of the
      minimum angle of resolution, IVD group 0.21 +/- 0.26 vs. IVB group 0.39 +/- 0.30,
      p = 0.038) and the 1-month CMT was thinner in the IVD group (IVD group 270.0 +/-
      62.0 MUm vs. IVB group 338.9 +/- 122.6 MUm, p = 0.028), and these trends were
      maintained during the 6-month follow-up. The IVD group showed more rapid macular
      edema resolution (p = 0.049); however, there were no significant differences in
      ellipsoid zone recovery rate (p = 0.268) or ganglion cell-inner plexiform layer
      volume between the two groups (p = 0.459). CONCLUSIONS: There were no significant
      differences in final visual or anatomical outcomes between the two groups;
      however, initial dexamethasone implant injection followed by bevacizumab PRN
      injection initially showed more rapid improvement in vision and BRVO-associated
      macular edema resolution compared to intravitreal bevacizumab administered
      monthly on a PRN basis.

PMID- 29376224
TI  - Long-term Efficacy of Botulinum Neurotoxin-A Treatment for Essential
      Blepharospasm.
AB  - PURPOSE: In the present study, we investigated the treatment efficacy and
      clinical outcomes of botulinum neurotoxin-A (BoNT-A) administered for longer than
      5 years to patients with essential blepharospasm. METHODS: We retrospectively
      reviewed 19 patients (male : female = 8 : 11) diagnosed with essential
      blepharospasm between March 2006 and July 2016 who underwent BoNT-A injections
      for over 5 years and were followed. Efficacy of 297 injections of Botox (n =
      162), Meditoxin (n = 75), Hugel-tox (n = 40), or Dysport (n = 20) was based on
      the symptom improvement score at the final injection (-1, worse; 0, same; 1,
      better). Injection dose (botox unit), duration of efficacy (months), and adverse
      events were also investigated. RESULTS: Based on product type, significant
      differences in patient age (59.3 +/- 9.8 years), disease period (5.0 +/- 5.4
      years), number of botulinum neurotoxin injections before visiting our clinic (1.6
      +/- 2.6), and follow-up period (7.2 +/- 1.6 years) were not observed. Treatment
      efficacy score and injection dose of repetitive injections were 0.1 +/- 0.5 and
      39.1 +/- 4.0 units, respectively, and did not show significant differences with
      repeated injections. Duration of response was 5.9 +/- 5.4 months, but this
      significantly decreased as the injections were repeated (p < 0.01). Among the 297
      injections, adverse events occurred 12 times (4.0%) with no severe sequelae.
      CONCLUSIONS: In this study, we showed that repetitive, long-term BoNT-A
      injections are considered a stable and effective treatment for essential
      blepharospasm in terms of consistent injection dose and maintenance of treatment
      efficacy. However, the duration of long-term efficacy could be decreased in
      patients injected repetitively.

PMID- 29376225
TI  - Factors Affecting ISNT Rule Satisfaction in Normal and Glaucomatous Eyes.
AB  - PURPOSE: To determine the factors that influence the satisfaction of the 'ISNT
      rule' (neural rim width: inferior >= superior >= nasal >= temporal) in normal and
      glaucomatous eyes. METHODS: The medical records of patients that visited Boramae
      Medical Center, Seoul, Korea, were reviewed. Each group of normal and
      glaucomatous eyes was divided into subgroups based on whether or not they
      satisfied the ISNT rule. ISNT rule assessment was performed by measuring the rim
      width with stereoscopic optic disc photographs using ImageJ software. Logistic
      regression analysis was performed to determine the factors that affect ISNT rule
      satisfaction. RESULTS: Seventy-seven normal eyes and 97 glaucomatous eyes were
      included in the study. The ISNT rule was intact in 59 (76.6%) of the normal eyes
      and was violated in 71 (73.2%) of the glaucomatous eyes. Logistic regression
      analysis revealed a significant influence of axial length in violation of the
      ISNT rule in the normal eye group, while the mean deviation value was a
      significant factor for violation of the ISNT rule in the glaucomatous eye group.
      CONCLUSIONS: The ISNT rule should be cautiously applied when evaluating normal
      eyes with long axial lengths. In addition, the ISNT rule might not be as
      effective for detecting early glaucoma.

PMID- 29376226
TI  - Temporary Haptic Externalization and Four-point Fixation of Intraocular Lens in
      Scleral Fixation to Enhance Stability.
AB  - PURPOSE: To report the results of a new technique for intraocular lens scleral
      fixation of temporary haptic externalization and four-point fixation for enhanced
      stability. METHODS: Two 10-0 polypropylene strands were fixed at two points 2 mm
      apart on each haptic of a conventional three-piece intraocular lens, using our
      previously reported method of temporary haptic externalization after injector
      implantation. Postoperative refractive outcome and stability were evaluated.
      RESULTS: Although the intraocular lens was fixed at a total of four points, no
      intraoperative difficulties were observed during the process. Patients showed
      successful fixation of the intraocular lens postoperatively. The fixed
      intraocular lens showed good centering and minimal tilting. When compared to the
      two-point fixation technique, postoperative astigmatism was significantly smaller
      in the four-point fixation group (1.80 +/- 0.84 vs. 1.00 +/- 0.0.50, p = 0.033).
      Lens-induced astigmatism calculated from subtraction of corneal astigmatism from
      total astigmatism was also significantly smaller in the four-point fixation group
      (2.23 +/- 0.98 vs.1.17 +/- 0.0.70, p = 0.043). No postoperative complications
      were identified during a mean follow-up period of 14.8 months (range, 10 to 19
      months). CONCLUSIONS: By fixing the intraocular lens at two points on each side
      of the haptics, this method minimizes the tilting of the intraocular lens and
      thus decreases postoperative lens-induced astigmatism. Also, the possibility of
      intraocular lens dislocation in the long term might be decreased by this two
      point fixation technique.

PMID- 29376227
TI  - Effects of Surgical Assistant's Level of Resident Training on Surgical Treatment
      of Intermittent Exotropia: Operation Time and Surgical Outcomes.
AB  - PURPOSE: To evaluate the effects of the surgical assistant's level of resident
      training on operation time and surgical outcome in the surgical treatment of
      intermittent exotropia. METHODS: This study included 456 patients with
      intermittent exotropia who underwent lateral rectus recession and medial rectus
      resection and were followed up for 24 months after surgery. The patients were
      divided into two groups according to the surgical assistant's level of resident
      training: group F (surgery assisted by a first-year resident [n = 198]) and group
      S (surgery assisted by a second-, third-, or fourth-year resident [n = 258]). The
      operation time and surgical outcomes (postoperative exodeviation and the number
      of patients who underwent a second operation) were compared between the two
      groups. RESULTS: The average operation times in groups F and S were 36.54 +/- 7.4
      and 37.34 +/- 9.94 minutes, respectively (p = 0.33). Immediate postoperative
      exodeviation was higher in group F (0.79 +/- 3.82 prism diopters) than in group S
      (0.38 +/- 3.75 prism diopters). However, repeated-measures analysis of variance
      revealed no significant difference in exodeviation between the two groups during
      the 24-month follow-up period (p = 0.45). A second operation was performed in
      29.3% (58 / 198) of the patients in group F, and in 32.2% (83 / 258) of those in
      group S (p = 0.51). CONCLUSIONS: No significant difference in operation time was
      observed when we compared the effects of the level of resident training in the
      surgical treatment of intermittent exotropia. Although the immediate
      postoperative exodeviation was higher in patients who had undergone surgery
      assisted by a first-year resident, the surgical outcome during the 24-month
      follow-up was not significantly different.

PMID- 29376228
TI  - Myopic Shift after Implantation of a Novel Diffractive Trifocal Intraocular Lens
      in Korean Eyes.
AB  - PURPOSE: To evaluate the clinical outcomes of cataract surgery using novel
      diffractive trifocal intraocular lenses (IOLs) in Koreans. METHODS: This was a
      retrospective, consecutive, interventional study of cataract surgery using POD
      FineVision IOL implantation. Complete ophthalmologic examinations were performed
      preoperatively and postoperatively. Defocus curves were assessed over a range of
      +1.5 to -4.0 diopters in 0.5-diopter steps at one month postoperatively.
      Uncorrected distant visual acuity, uncorrected intermediate visual acuity,
      uncorrected near visual acuity, corrected distant visual acuity, distant
      corrected intermediate visual acuity, and distant-corrected near visual acuity
      were assessed one month postoperatively, and manifest refraction was performed
      during every visit. RESULTS: The study analyzed 31 eyes in 20 patients. There
      were statistically significant improvements in uncorrected distance visual
      acuity, uncorrected intermediate visual acuity, uncorrected near visual acuity,
      corrected distance visual acuity, distance-corrected intermediate visual acuity,
      and distance-corrected near visual acuity (p < 0.001). The final postoperative
      refractive outcomes showed statistically significant myopic shifts compared to
      the target refraction based on SRK/T, SRK-II, Haigis, and Hoffer Q formulas (p <
      0.001). CONCLUSIONS: POD FineVision IOLs provide stable visual restoration with
      improvements of near and intermediate vision in presbyopic eyes. POD FineVision
      IOLs show myopic shift in a Korean population; therefore, surgeons should be
      cautious when selecting IOL power in such patients.

PMID- 29376229
TI  - Investigation of the Changes in Refractive Surgery Trends in Korea.
AB  - PURPOSE: To evaluate changes in clinical practice in the field of refractive
      surgery in Korea over the past 10 years. METHODS: A survey consisting of 59
      multiple-choice questions regarding the preferred types of refractive surgery,
      excimer laser machine, and presbyopia surgery was mailed to 742 members of the
      Korean Society of Cataract and Refractive Surgery in January 2016, and 50 members
      responded to the survey. These data were compared with the 2005 or 2007 survey
      results. RESULTS: The majority of respondents were in their 40s (54%), and the
      average number of refractive surgeries performed in one month was 53. The most
      commonly used excimer laser machine was the VISX S4 in both 2005 (32%) and 2015
      (25%); however, a greater variety of machines (EX500 [18%], Allegretto wave Eye-Q
      [13%], AMARIS 750 [10%]) were used in 2015. The preferred corneal refractive
      surgery in 2015 was surface ablation (40%), representing a significant increase
      in its popularity compared to 2005 (15%) (p < 0.001). The popularity of laser in
      situ keratomileusis (LASIK) surgery decreased to 20% in 2015 compared to 48% in
      2005 (p < 0.001). Eighty percent of LASIK procedures in 2015 were performed using
      femtosecond laser. In 2015, surface ablation and phakic intraocular lens
      implantation were preferred for the treatment of myopia less than -8 diopters and
      more than -8 diopters, respectively. The proportion of respondents performing
      presbyopia surgery in 2015 (76%) was significantly increased from 2007 (30%) (p <
      0.001). CONCLUSIONS: Over the past decade, the most commonly performed corneal
      refractive surgery has changed from LASIK to surface ablation, and there has been
      a significant increase in the popularity of presbyopia surgery.

PMID- 29376230
TI  - Anterior Segment Changes during Accommodation in Accommodative Esotropia.
AB  - PURPOSE: To evaluate the anterior segment biometric parameters of non
      accommodative and accommodative refractive accommodative esotropia (RAE).
      METHODS: Eighty-one eyes of 81 patients were included in this prospective, case
      control study. The patients were divided into three groups as follows: the RAE
      group (n = 31), the hypermetropia group (n = 25), and the emmetropia group (n =
      25). Measurements were obtained in the non-accommodative (0.0 diopters) and
      accommodative status (-5.0 diopters) using a Pentacam HR. The anterior chamber
      depth (ACD), anterior chamber volume (ACV), pupil diameter (PD), and anterior
      chamber angle (ACA) were evaluated at all four quadrants. RESULTS: The ACD, ACV
      and PD values in the RAE group were lower than those of the other groups in both
      states (p < 0.05). The ACD values were lower in the hypermetropia group than in
      the emmetropia group for the non-accommodative status (p = 0.024) but were
      similar for the accommodative status (p = 0.225). PD and ACV values were lower in
      the hypermetropia group than in the emmetropia group in both states (non
      accommodative status, p = 0.011 and p = 0.022; accommodative status, p = 0.026
      and p = 0.034, respectively). Changes in ACD, ACV and PD during accommodation
      (Delta) were not significant in the RAE group but were significant for the other
      groups (hypermetropia: DeltaACD, p = 0.001; DeltaACV, p = 0.001; DeltaPD, p =
      0.002; emmetropia: DeltaACD, p < 0.001; DeltaACV, p = 0.001; DeltaPD, p < 0.001).
      These changes were significantly lower in the hypermetropia group than in the
      emmetropia group (DeltaACD, p = 0.012; DeltaACV, p = 0.031; DeltaPD, p = 0.034).
      CONCLUSIONS: The anterior chamber in RAE patients was shallower and the increase
      in convexity of the anterior surface or forward movement of the crystalline lens
      was more limited during accommodation in RAE.

PMID- 29376231
TI  - Diabetic Retinopathy in the Asia-Pacific.
AB  - Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is
      the leading cause of new cases of blindness in middle-aged and elderly in the
      Asia-Pacific. It has been estimated that 51% of all those with blindness due to
      DR globally (n = 424,400) and 56% of those with visual impairment due to DR (2.1
      million) come from the Asia-Pacific. Prevalence of DR among those with diabetes
      ranged from 10% in India to 43% in Indonesia within the Asia-Pacific. Awareness
      of DR among persons with diabetes ranged from 28% to 84%. Most common modifiable
      risk factors for DR in the Asia-Pacific were hyperglycemia, blood pressure,
      dyslipidemia, and obesity. Implementation of systematic screening programs for DR
      and advancement in telemedicine screening methods have increased patient coverage
      and cost-effectiveness, though there are still numerous factors impeding
      screening uptake in the low-middle income regions of the Asia-Pacific. Management
      and treatment of DR in the Asia-Pacific is mainly limited to traditional laser
      retinopexy, but it is suboptimal despite new clinical approaches such as use of
      intravitreal anti.vascular endothelial growth factor and steroids due to limited
      resources. Further research and data are required to structure a more cost
      effective public healthcare program and more awareness-building initiatives to
      increase the effectiveness of DR screening programs.

PMID- 29376232
TI  - The Role of Teleophthalmology in the Management of Diabetic Retinopathy.
AB  - The emergence of diabetes as a global epidemic is accompanied by the rise in
      diabetes-related retinal complications. Diabetic retinopathy, if left undetected
      and untreated, can lead to severe visual impairment and affect an individual's
      productivity and quality of life. Globally, diabetic retinopathy remains one of
      the leading causes of visual loss in the working-age population.
      Teleophthalmology for diabetic retinopathy is an innovative means of retinal
      evaluation that allows identification of eyes at risk for visual loss, thereby
      preserving vision and decreasing the overall burden to the health care system.
      Numerous studies worldwide have found teleophthalmology to be a reliable and cost
      efficient alternative to traditional clinical examinations. It has reduced
      barriers to access to specialized eye care in both rural and urban communities.
      In teleophthalmology applications for diabetic retinopathy, it is critical that
      standardized protocols in image acquisition and evaluation are used to ensure low
      image ungradable rates and maintain the quality of images taken. Innovative
      imaging technology such as ultrawide field imaging has the potential to provide
      significant benefit with integration into teleophthalmology programs.
      Teleophthalmology programs for diabetic retinopathy rely on a comprehensive and
      multidisciplinary approach with partnerships across specialties and health care
      professionals to attain wider acceptability and allow evidence-based eye care to
      reach a much broader population.

PMID- 29376233
TI  - Management of Retinopathy of Prematurity--Use of Anti-VEGF Therapy.
AB  - Retinopathy of prematurity (ROP) is a leading cause of childhood blindness
      worldwide. Although laser photocoagulation re-mains the gold standard for
      treating threshold and prethreshold disease (type 1 ROP), the off-label use of
      anti-vascular endothelial growth factor (anti-VEGF) therapy to treat ROP is
      increasing. Benefits include acute regression of ROP, growth of retinal
      vasculature beyond the demarcation line, lesser degree of myopia and peripheral
      visual field loss, and avoidance of sedation and intubation required for laser.
      However, controversies regarding anti-VEGF in this vulnerable population persist
      including choice of anti-VEGF agent, dosing, systemic absorption, safety, and
      late recurrence. This review updates recent evidence regarding the use of anti
      VEGF therapy in the management of ROP.

PMID- 29376235
TI  - [Study on the mechanism of Bushen Culuan Chongji treating "kidney deficiency and
      blood stasis" in ovulatory dysfunctional infertility].
AB  - Kidney deficiency and blood stasis is the main cause of ovulatory dysfunctional
      infertility. Kidney deficiency is the main pathological mechanism. Blood stasis
      is the main pathological manifestation, and it is an important factor throughout.
      Bushen Culuan Chongji is under the guidance of traditional Chinese medicine(TCM)
      theory, previous years of clinical experience, combined with the etiology and
      pathogenesis of anovulatory infertility and modern pharmacological research
      results, selected, not only maintains the TCM syndrome differentiation and
      different diseases features, but also reflects the superiority of the combination
      of disease. In the study of Bushen Culuan Chongji in the treatment of anovulatory
      infertility, there was no acute toxicity and no LD50 was detected. No adverse
      effects and side effects were found in the reproductive, genetic, toxicity,
      teratogenic, and perinatal tests in their high and low dose groups. In
      pharmacodynamics experiments, it can promote the development and maturation of
      follicles and the formation of corpus luteum in rats. Taking the kidney
      deficiency and blood stasis syndrome as the breakthrough point, systematically
      study the efficacy, safety and mechanism of six ovulatory dysfunctional
      infertility diseases, including abnormal uterine bleeding-ovulatory disorders,
      polycystic ovary syndrome, high prolactin, luteinized unruptured follicle
      syndrome, luteal phase defect and diminished ovarian reserve/premature ovarian
      failure. It verified the contribution degree of reinforcing kidney and resolving
      stasis TCM, reflected the characteristics of combination between disease
      differentiation and syndrome differentiation, interpreted the treatment
      principles of treating different diseases with the same method, and provided
      scientific basis for clinical treatment.

PMID- 29376234
TI  - Multimodal Imaging in Diabetic Macular Edema.
AB  - Throughout ophthalmic history it has been shown that progress has gone hand in
      hand with technological breakthroughs. In the past, fluorescein angiography and
      fundus photographs were the most commonly used imaging modalities in the
      management of diabetic macular edema (DME). Today, despite the moderate
      correlation between macular thickness and functional outcomes, spectral domain
      optical coherence tomography (SD-OCT) has become the DME workhorse in clinical
      practice. Several SD-OCT biomarkers have been looked at including presence of
      epiretinal membrane, vitreomacular adhesion, disorganization of the inner retinal
      layers, central macular thickness, integrity of the ellipsoid layer, and
      subretinal fluid, among others. Emerging imaging modalities include fundus
      autofluorescence, macular pigment optical density, fluorescence lifetime imaging
      ophthalmoscopy, OCT angiography, and adaptive optics. Technological advances in
      imaging of the posterior segment of the eye have enabled ophthalmologists to
      develop hypotheses about pathological mechanisms of disease, monitor disease
      progression, and assess response to treatment. Spectral domain OCT is the most
      commonly performed imaging modality in the management of DME. However, reliable
      biomarkers have yet to be identified. Machine learning may provide treatment
      algorithms based on multimodal imaging.

PMID- 29376236
TI  - [Treatment of anovulatory infertility by tonifying kidney and promoting blood
      circulation].
AB  - Infertility is a common disease in women of childbearing age and is also a
      refractory disease. Anovulatory dysfunction is one of the main causes of female
      infertility, and the incidence of anovulatory infertility has been increasing
      year by year. Traditional Chinese medicine has unique advantages and definite
      curative effect on the treatment of this disease. Kidney deficiency is the basic
      pathogenesis and blood stasis is an important factor that has been through.
      Flexible of tonifying the kidney and promoting blood circulation treatment of
      anovulatory infertility in clinic, has achieved remarkable curative effect.
      Kidney deficiency and blood stasis is a common form of gynecological disease.
      After years of clinical practice, we also found that patients with anovulatory
      infertility were more common with kidney deficiency and blood stasis. The kidneys
      and blood are not isolated from each other, but interact and influence each
      other. Kidney deficiency and blood stasis interact as both cause and effect, they
      have very close relationship. To achieve the purpose of urinary Tiangui,
      Chongren, ovulation and pregnancy miscarriage by tonifying the kidney and
      promoting blood circulation.

PMID- 29376237
TI  - [Application of kidney deficiency and blood stasis and disharmony between heart
      and kidney theories in patients with sleep disorders in perimenopause].
AB  - Perimenopausal syndrome refers to a series of physical and mental symptoms,
      caused by the fluctuation of the sex hormones in the menopause, which is one of
      the common diseases in gynecology. The incidence of sleep disorders in
      perimenopausal women is increasing significantly. Both Chinese medicine and
      Western medicine are trying to exploring its pathologic mechanism to find the
      safe and effective methods of treatment. Menopausal sleeping disorder is the same
      as the perimenopause syndrome and insomnia category in traditional Chinese
      medicine. Kidney deficiency is the basic characteristic of perimenopause, whether
      kidney essence, kidney Qi, kidney Yin or kidney Yang can lead to blood stasis. It
      is believed that this disease results from kidney deficiency in the root and
      blood stasis in the tip, and on this basis women affected by many factors will
      result in disharmony between heart and kidney. In clinical practice, The method
      of tonifying kidney and activating blood applied to treat perimenopause syndrome
      with insomnia was testified to be effective. Therefore the author thought that
      kidney deficiency and blood stasis and disharmony between heart and kidney were
      the key factors of patients with insomnia in perimenopause.

PMID- 29376238
TI  - [Features of Professor Ma Kun's medication in treating ovulatory infertility].
AB  - In order to analyze Professor Ma Kun's medication in treating anovulatory
      infertility, her prescriptions for treating anovulatory infertility in 2012-2015
      were collected. The medication features and the regularity of prescriptions were
      mined by using traditional Chinese medicine inheritance support system,
      association rules, complex system entropy clustering and other mining methods.
      Finally, a total of 684 prescriptions and 300 kinds of herbs were screened out,
      with a total frequency of 11 156 times; And 68 core combinations and 8 new
      prescriptions were mined. The top three frequently used herbs by effect were
      respectively tonic herb, blood circulation promoting herb, and Qi-circulation
      promoting herb. The top three tastes were sweetness, bitterness and pungent
      flavor. The results showed 28 herbs with a high frequency of >=100.The top 10
      frequently used herbs were respectively Angelica Sinensis Radix, Cyperi Rhizoma,
      Chuanxiong Rhizome, Paeoniae Radix Rubra, Cyathulae Radix, Taxilli Herba,
      Cuscutae Semen, Codonopsis Radix, Ligustri Lucidi Fructus, Paeoniae Albaand
      Paeoniae Radix Alba. The association rules analysis showed commonly used herbal
      pairs, including Rehmanniae Radix Preparata-Chuanxiong Rhizome, Rehmanniae Radix
      Preparata-Angelica Sinensis Radix, Cuscutae Semen-Dipsaci Radix. In conclusion,
      Professor Ma has treated anovulatory infertility by nourishing the kidney and
      activating blood throughout the treatment course, and attached the importance to
      the relationship between Qi and blood and there gulation of liver, spleen and
      kidney in treating anovulatory infertility.

PMID- 29376239
TI  - [Systematic review on Bushen Huoxue ricipe in treating patients suffering from
      diminished ovarian reserve].
AB  - To systematically evaluate the efficacy and safety of Bushen Huoxue ricipe in
      treating patients suffering from diminished ovarian reserve. Databases such as
      CNKI, WanFang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched on
      randomized controlled trial/quasi-randomized controlled trial about Bushen Huoxue
      ricipe in treating patients suffering from diminished ovarian reserve form the
      inception of the study until June 2017. The studies were screened according to
      inclusion and exclusion criteria. Risk of bias evaluation tools were adopted to
      conduct quality evaluation. Meta-analysis on outcome indicator was performed by
      RevMan Version 5.3 Software. Due to the different Bushen Huoxue recipe
      (observation group) and the different Western medicine(control group) of all
      included studies, the effect size was combined by the random effect model after
      the subgroup analysis or sensitivity analysis was performed. Eventually 11 trials
      were included, including 733 cases of patients. Results of Meta-analysis
      indicated that, Bushen Huoxue recipe had advantages over Western medicine on
      lowering FSH, increasing AMH and AFC, enhancing the Chinese medicine symptom
      curative effect; Bushen Huoxue recipe had no advantages over Western medicine on
      increasing E2; the advantages of Bushen Huoxue recipe were not clear on reducing
      FSH/LH and increasing total effective rate because of the different outcomes to
      compared with the different Western medicine; no serious adverse reaction
      appering from Bushen Huoxue recipe was reported in the including researches.
      Bushen Huoxue recipe has the clinical curative effect and high safety suffering
      from diminished ovarian reserve. However, limited by the poor quantity of
      studies, these conclusions remain to be examined by more center, more sample and
      high-quality studies.

PMID- 29376240
TI  - [Impact of prostaglandin F2alpha and endothelin, pulsation index and resistance
      index of uterine artery blood flow on dysmenorrhea patients of cold stagnation
      and blood stasis syndrome with Dingkun Dan].
AB  - This research apply Dingkun Dan to treat patients with dysmenorrhea of cold
      stagnation and blood stasis syndrome. This study observed its effectiveness and
      safety of the treatment of the disease and its influence on the serum
      prostaglandin F2alpha, endothefin, pulsatility index and resistant index of
      uterine artery blood, to explore the possible mechanism of effect of Dingkun Dan
      in the treatment of dysmenorrhea and provide scientific basis for clinical
      application. The 75 patients with dysmenorrhea of cold stagnation and blood
      stasis who met the inclusion criteria, were divided into treatment group (n=37)
      and control group (n=38) by using random number remainder grouping method. In the
      treatment group patients were treated with Dingkun Dan, the other group were
      given Fuke Zaizao Jiaonang. Two groups have same time to take the medicine, three
      days prior to the menstruation for ten days. Medication for three menstrual
      cycles was seen as a course of treatment. To observe and compare the two groups
      of patients before and after treatment VAS score, syndrome integral, serum levels
      of prostaglandin F2alpha and endothelin, pulsation index and resistance index of
      uterine artery blood flow and related safety index changes. Finally makes
      statistical analysis. It has been identified that, Treatment group and control
      group can reduce pain symptom of dysmenorrhea patients and improve the syndromes
      scores, compare with control group, effect of the treatment group is more
      significant(P<0.01). VAS pain curative effect: the treatment group and control
      group total effective rate respectively were, 97.22%, 69.44%, markedly effective
      rate were 83.33%, 30.56%, comparison between two groups, treatment group is
      better than that of control group(P<0.01). Syndromes curative effect: the
      treatment group and control group total effective rate respectively were 97.22%,
      94.44%, markedly effective rate was 66.67%, 2.78%, respectively. The comparison
      between two groups, the total effective rate has no obvious difference, but
      markedly effective rate of treatment group is better than that of control
      group(P<0.01). The treatment group can significantly reduce the patients' serum
      level of prostaglandin F2alpha(P<0.01), but no obvious difference was found in
      the control group before and after treatment. Both groups can significantly
      reduce the serum level of endothelin(P<0.01), comparison between two groups, the
      treatment group is more significant(P<0.01).Both treatment group and control
      group were significantly lower left and right pulsation index and resistance
      index of uterus artery blood flow(P<0.01). Between groups to compare the effect,
      the treatment group is more significant(P<0.01). Both treatment group and control
      group in the security check before and after treatment found no significant
      anomalies. Dingkun Dan in treating dysmenorrhea with cold stagnation and blood
      stasis syndrome seems to have remarkable clinical curative effect and safety,
      which may be achieved by significantly reducing the serum level of prostaglandin
      F2alphaand endothefin of the patients, and reducing the pulsation index and
      resistance index of uterine artery blood flow of the patients, to improve uterine
      artery condition of blood, and correcting local tissue ischemia to relieve pain.

PMID- 29376241
TI  - [Discussion on research thinking of traditional Chinese medicine standardization
      system based on whole process quality control].
AB  - The concept of "Quality by design" indicates that good design for the whole life
      cycle of pharmaceutical production enables the drug to meet the expected quality
      requirements. Aiming at the existing problems of the traditional Chinese medicine
      (TCM) industry, the TCM standardization system was put forward in this paper from
      the national strategic level, under the guidance by the idea of quality control
      in international manufacturing industry and with considerations of TCM industry's
      own characteristics and development status. The connotation of this strategy was
      to establish five interrelated systems: multi-indicators system based on tri
      indicators system, quality standard and specification system of TCM herbal
      materials and decoction pieces, quality traceability system, data monitoring
      system based on whole-process quality control, and whole-process quality
      management system of TCM, and achieve the whole process systematic and scientific
      study in TCM industry through "top-level design-implement in steps-system
      integration" workflow. This article analyzed the correlation between the quality
      standards of all links, established standard operating procedures of each link
      and whole process, and constructed a high standard overall quality management
      system for TCM industry chains, in order to provide a demonstration for the
      establishment of TCM whole-process quality control system and provide systematic
      reference and basis for standardization strategy in TCM industry.

PMID- 29376242
TI  - [Development of whole process quality control and management system of
      traditional Chinese medicine decoction pieces based on traditional Chinese
      medicine quality tree].
AB  - The whole process quality control and management of traditional Chinese medicine
      (TCM) decoction pieces is a system engineering, involving the base environment,
      seeds and seedlings, harvesting, processing and other multiple steps, so the
      accurate identification of factors in TCM production process that may induce the
      quality risk, as well as reasonable quality control measures are very important.
      At present, the concept of quality risk is mainly concentrated in the aspects of
      management and regulations, etc. There is no comprehensive analysis on possible
      risks in the quality control process of TCM decoction pieces, or analysis summary
      of effective quality control schemes. A whole process quality control and
      management system for TCM decoction pieces based on TCM quality tree was proposed
      in this study. This system effectively combined the process analysis method of
      TCM quality tree with the quality risk management, and can help managers to make
      real-time decisions while realizing the whole process quality control of TCM. By
      providing personalized web interface, this system can realize user-oriented
      information feedback, and was convenient for users to predict, evaluate and
      control the quality of TCM. In the application process, the whole process quality
      control and management system of the TCM decoction pieces can identify the
      related quality factors such as base environment, cultivation and pieces
      processing, extend and modify the existing scientific workflow according to their
      own production conditions, and provide different enterprises with their own
      quality systems, to achieve the personalized service. As a new quality management
      model, this paper can provide reference for improving the quality of Chinese
      medicine production and quality standardization.

PMID- 29376243
TI  - [Discover potential inhibitors of 5-LOX and LTA4H from Rhei Radix et Rhizoma,
      Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix based on molecular
      simulation methods].
AB  - 5-lipoxygenase (5-LOX) and leukotriene A4 hydrolase (LTA4H), as the major targets
      of 5-LOX branch in the arachidonic acid (AA) metabolic pathway, play an important
      role in the treatment of inflammation. Rhei Radix et Rhizoma, Notopterygii
      Rhizoma et Radix and Genitana Macrophyllae Radix have clear anti-inflammation
      activities. In this paper, the targets of 5-LOX and LTA4H were used as the
      research carrier, and Hiphop module in DS4.0 (Discovery studio) was used to
      construct ingredients database for preliminary screening of three traditional
      Chinese medicines based on target inhibitor pharmacophore, so as to obtain 5-LOX
      and LTA4H potential active ingredients. The ingredients obtained in initial
      pharmacophore screening were further screened by using CDOCKER module, and the
      screening rules were established based on the score of initial compound and the
      key amino acids to obtain 12 potential 5-LOX inhibitors and 7 potential LTA4H
      inhibitors. To be more specific, the potential 5-LOX inhibitors included 6
      ingredients in Rhei Radix et Rhizoma, such as procyanidins B2-3,3'-O-double
      gallate and revandchinone 2; four ingredients in notopterygium, such as
      dodecanoic acid and so on. On the other hand, potential LTA4H inhibitors included
      revandchinone 1, revandchinone 4 in Rhei Radix et Rhizoma, tridecanoic acid,
      tetracosanoic acid and methyl eicosanoate in Notopterygii Rhizoma et Radix,
      montanic acid methyl ester and N-docosanoyl-O-aminobenzoate in Genitana
      Macrophyllae Radix and so on. The molecular simulation methods were highly
      efficient and time-saving to obtain the potential inhibitors of 5-LOX and LTA4H,
      which could provide assistance for discovering the chemical quality indicators of
      anti-inflammatory efficacy of three Chinese herbs, and may be helpful to promote
      the whole-process quality control of three Chinese herbs.

PMID- 29376244
TI  - [Preliminary study on standardization of production and processing of Angelicae
      Sinensis Radix pieces].
AB  - Study on the standardization of Chinese materia medica is an important action for
      modernization and globalization for traditional Chinese medicine. Standardization
      on the processing of Chinese herbal pieces is an important part in the study on
      standardization of Chinese materia medica, so it is of great significance to
      establish the technical processing standards of Angelicae Sinensis Radix pieces
      for improving its quality. In this study, single factor experiment was designed
      to optimize the softening, cutting and drying processes of Angelicae Sinensis
      Radix. With ferulic acid, Angelicae Sinensis Radix polysaccharide, volatile oil
      and extracts (water and ethanol) content as the quality index, the effects of
      different softening, cutting and drying processes on the contents of the five
      components in Angelicae Sinensis Radix were analyzed, and the normalized distance
      evaluation method was used to analyze the experimental data. The results showed
      that the content of five components in Angelicae Sinensis Radix was affected by
      different softening methods and drying temperature, but the thickness of slice
      had little effect on the content. The best preparation process for Angelicae
      Sinensis Radix was as follows: Non-medicinal parts were removed; mildewed and rot
      as well as moth-eaten parts were removed; washed by the flowing drinking water;
      stacked in the drug pool; moistening method was used for softening, where 125 mL
      water was sprayed for every 1 kg of herbs every 2.5 h; upper part of herbs
      covered with clean and moist cotton, and cut into thin slices (1-2 mm) after 15 h
      moistening until appropriate softness, with disk thickness of 1-2 cm, then
      received blast drying for 6 h at 55 C, and turned over for 2 times during the
      drying.

PMID- 29376245
TI  - [Standardization of production of process Notopterygii Rhizoma et Radix slices].
AB  - Notopterol, isoimperatorin, volatile oil and extract (water and ethanol) were
      used as the research objects in this study to investigate the effects of
      different softening method, slice thickness and drying methods on the quality of
      Notopterygii Rhizoma et Radix slices, and the experimental data were analyzed by
      homogeneous distance evaluation method. The results showed that different
      softening, cutting and drying processes could affect the content of five
      components in Notopterygii Rhizoma et Radix incisum. The best processing
      technology of Notopterygii Rhizoma et Radix slices was as follows: non-medicinal
      parts were removed; mildewed and rot as well as moth-eaten parts were removed;
      washed by the flowing drinking water; stacked in the drug pool; moistening method
      was used for softening, where 1/8 volume of water was sprayed for every 1 kg of
      herbs every 2 h; upper part of herbs covered with clean and moist cotton, and cut
      into thick slices (2-4 mm) after 12 h moistening until appropriate softness, then
      received blast drying for 4 h at 50 C, and turned over for 2 times during the
      drying. The process is practical and provides the experimental basis for the
      standardization of the processing of Notopterygii Rhizoma et Radix, with great
      significance to improve the quality of Notopterygii Rhizoma et Radix slices.

PMID- 29376246
TI  - [Simultaneous content determination of 14 components in Rhei Radix et Rhizoma by
      high performance liquid chromatography method].
AB  - To establish an HPLC (high performance liquid chromatography) method for the
      simultaneous content determination of gallic acid, (+)-catechin, (-)-epicatechin
      3-O-gallate, isolindleyin, 4-(4'-hydroxyphenyl)-2-butanone, emodin, chrysophanol,
      physcion, aloe-emodin, rhein, lindleyin, 4-(4'-hydroxyphenyl)-2-butanone-4'-O
      beta-D-(2"-O-galloyl-6"-O-cinnamoyl)-glucopyranoside, sennoside A and sennoside B
      in Rhei Radix et Rhizoma. The analysis was performed on Agilent Zorbax SB-C18
      (4.6 mm*150 mm, 5 MUm) with 0.05% phosphoric acid solution (A) - acetonitrile (B)
      as mobile phase for gradient elution. The flow rate was 1 mL*min-1, with column
      temperature of 40 C and the wavelength was set at 268 nm. All calibration curves
      showed good linearity (r > 0.999 9) within the concentration range. Both the
      intra- and inter-day precision for 14 analytes was less than 3.1%, with the mean
      recovery at the range of 91.80%-104.1%. Meanwhile, quantitative determination was
      carried out for 10 qualified samples from Rheum palmatum and 10 qualified samples
      from R. tanguticum, respectively. It was found that the content of 4-(4'
      hydroxyphenyl)-2-butanone and aloe-emodin were higher in the R. tanguticum and R.
      palmatum, respectively, and the content of all the compounds was different in
      each sample. The established HPLC method for simultaneous content determination
      of 14 compounds from Rhei Radix et Rhizoma could be used for quantitative
      assessment and quality control of Rhei Radix et Rhizoma.

PMID- 29376247
TI  - [How to draft editorial explanation for transparent and concise guideline on
      clinical practice--Case analysis].
AB  - Clinical practice guideline (CPG) should be concise and readability, which can be
      possible to implement CPG into practice smoothly. A formal published CPG can't
      load its developing process and details. An editorial explanation of CPG is much
      useful to show details and logic process of developing CPG. Although there are
      many different standards for developing CPG, being nothing to do with process
      management of CPG. By referring to editorial explanation on international
      standards, a request for CPG was investigated in this study. An editorial
      explanation for clinical practice guideline should be transparency, logic and
      traceable. A good editorial explanation could make users or readers to learn what
      goes on behind the scenes. A standardized editorial explanation could supervise
      the GCP developing and improve the quality of GCP.

PMID- 29376248
TI  - [Research progress of Chinese herbs inhibiting NADPH oxidase].
AB  - Oxidative damage mediated by the abnormal activation of NADPH oxidase and the
      resulting excessive ROS generation is the pathogenesis for various diseases.
      Chinese herbs can play a role in the antioxidant treatment by inhibiting NADPH
      oxidase, which is meaningful for the treatment of pathological conditions such as
      injury of tissues, blood vessels and nerves, atherosclerosis, ischemia
      reperfusion, hypertension and hyperglycemia. In this paper, different forms of
      Chinese herbs including monomers, compounds and Chinese patent medicines with the
      inhibitory effect against NADPH oxidase would be reviewed, in order to explain
      and generalize their possible functions and the target mechanism for inhibition.

PMID- 29376249
TI  - [Application of reverse molecular docking technology in target prediction, active
      ingredient screening and action mechanism exploration of traditional Chinese
      medicine].
AB  - Traditional Chinese medicine(TCM) modernization has gradually become a worldwide
      trend. Reverse docking technology has also gradually become a useful tool for TCM
      modernization. It involves docking a small-molecule drug in the potential binding
      cavities of a set of clinically relevant macromolecular targets. Detailed
      analysis of the binding characteristics was used for the ranking of the targets
      according to the tightness of binding. This process can be used to potentially
      identify the novel molecular targets for the drug which may be relevant to its
      mechanism of action or side effect. In order to explore the action mechanism,
      screen the active ingredients and seek the treating target of TCM, reverse
      molecular docking technology has been widely used and has achieved remarkable
      results in recent years. In this review, we summarized the application of reverse
      molecular docking technology in the target seeking, active ingredients screening
      and potential mechanism exploration of TCM, which may provide more scientific
      basis for the clinical research and development of new herbal drugs.

PMID- 29376250
TI  - [Progress of regulation of leukemia stem cells of chronic myeloid leukemia by
      autophagy].
AB  - Leukemia stem cells (LSC) that were found in chronic myeloid leukemia (CML)
      responsible for the abnormal proliferation with the potential of self-renewal and
      multi-directional differentiation are involved in the pathophysiological process
      for drug resistance and relapse of CML. Autophagy, a conservative lysosomal
      degradation process that mediates cell degradation and recycling process, plays
      crucial roles in maintaining the homeostasis and function of intracellular
      environment. Recent studies suggested that autophagy is involved in the
      regulation of LSC differentiation and also closely related to the chemo
      sensitivity of CML. In this review, we focused on the role of autophagy on
      chemotherapy sensitivity of CML as well as the leukemia stem cell function for
      the development of new anti-leukemia drugs.

PMID- 29376251
TI  - [Current advance in cerebral malaria].
AB  - Cerebral malaria (CM), a severe neurological syndrome caused by Plasmodium
      falciparum infection, is a serious life-threatening disease with a high
      mortality. Survivors' persistent brain injury is manifested as long-term
      neurocognitive disorders. The main neuropathological feature of CM is the
      sequestration of parasited red blood cells (pRBCs) in cerebral microvessels.
      Other neuropathological features of CM include petechial hemorrhage in the brain
      parenchyma, annular hemorrhage, extensive brain endothelial cell activation, and
      focal endothelial cell injury and necrosis. However, its pathogenesis is still
      not clear. Currently, some studies have suggested that the pathogenesis of
      cerebral malaria mainly include pRBC adhesion, inflammatory reaction cascade,
      vascular leakage damage and brain hypoxia. Studies have shown that the biomarkers
      currently used as diagnostic and prognostic markers for CM include C-X-C motif
      chemokine ligand 10 (CXCL10), CXC chemokine ligand 4 (CXCL4), angiopoietin (Ang).
      In this paper, we systematically summarize the basic and clinical research for
      cerebral malaria in recent years and the latest literatures for drug studies, and
      focused on the advance of studies on cerebral malaria and its immunologic
      mechanism in the recent three years in the aspects of cytokines, immune cells,
      regulatory factors and biomarkers, so as to provide references for relevant
      studies.

PMID- 29376252
TI  - [Research progress on chemical constituents, pharmacological mechanism and
      clinical application of Guizhi decoction].
AB  - Guizhi Decoction was one of the most commonly used traditional Chinese Medicine
      which possesses the effects of "jie-ji-fa-biao, regulating Ying and Wei". It was
      mainly used to treat mind-cold due to exogenous evils such as fever, headache,
      sweating, hate the wind, et al. Modern studies indicated that the chemical
      constituents of Guizhi decoction mainly include phenylpropanoid, monoterpenes,
      organic acids, flavonoids, triterpenoid saponins and so on. Pharmacological
      experimental studies had shown that Guizhi decoction could play a big role in
      dual-directional regulation on sweat gland, body temperature, immune function,
      gastrointestinal peristalsis, and blood pressure, and could also play the role of
      anti-inflammatory, antibacterial, antiviral, anti-allergic, analgesic,
      hypoglycemic, and cardiovascular protection. Many diseases such as internal,
      external, gynecological and pediatric diseases were treated in the clinical by
      using Guizhi decoction and its analogous formulae involving circulatory, immune,
      urinary, reproductive, endocrine, digestive, nervous and other systems. This
      article reviews the latest research progress of Guizhi decoction from three
      aspects: chemical constituents, pharmacological mechanism and clinical
      application. It will provide reference for further research and development of
      Guizhi decoction.

PMID- 29376253
TI  - [Chemical constituents, biological activities and clinical applications of
      artemisia rupestris].
AB  - Artemisia rupestris is a traditional medicine in Uygur and Kazak in Xinjiang
      Province, mainly distributed in the territory of Xinjiang Altai area, Tianshan
      mountains and the Kunlun mountains, growing at an altitude of 1 500 to 4 000
      meters of grassland and forest areas. As the broad research on chemical
      constituents, pharmacological activity, the effective components of A. rupestris
      have attracted the interest to make up new drugs. Based on the latest research
      from A. rupestris, identification and geographic distribution, chemical
      constituents, pharmacological effects, clinical applications were summarized in
      this article, in the view of Medicinal Ethnobotany. At the same time, some
      suggestions were proposed for future research.

PMID- 29376254
TI  - [Effects of nitrogen on yields and flavonoids contents of Epimedium
      pseudowushanense in hydroponic conditions].
AB  - Nitrogen nutrition divided into concentrations and forms for Epimedium
      pseudowushanense was studied under hydroponic conditions. There were 7 nitrogen
      concentrations treatments(N0-N6)which nitrogen concentration was 0, 2.5, 5.0,
      7.5, 10.0, 13.0 mmol*L-1, respectively, and 5 nitrogen forms and proportions
      treatments (T1-T5) which NO3-N/NH4-N was 5?0, 4?1, 2.5?2.5, 1?4, 0?5
      respectively, the total nitrogen applied was 5 mmol*L-1. The results showed that
      along with the increase of nitrogen concentration, biomass (dry weight) and leaf
      dry weight increased, which in N5 treatment was 29%, 23% higher than those in N0
      and 36%, 23% higher than those in N4 respectively, but not significantly
      different from N6 treatment. Roots and stem dry weights did not change
      significantly. Pn and the contents of photosynthetic pigments were higher in N3
      N5 treatments. Epimedin A, B, C, icariin and total flavonoids contents were the
      lowest in N3 treatment, suddenly increase in N4 treatment and only a little
      change between N4-N6 treatments. N5 treatment with the highest epimedin C content
      was 131% higher than N3 treatment with the lowest epimedin C content (P<0.05).
      While in the nitrogen forms and proportions treatments, biomass, leaf and stem
      dry weights were the highest in T3 treatment and lower in T1 and T5 treatments,
      without significance between T1 and T5 treatments. These indicators in T3
      treatment were more than 30% higher than those in T1 treatment. The impact of
      nitrogen concentrations was greater than nitrogen forms on flavonoids. epmedin C
      content was the highest in T1 treatment, only 5%-8% higher than that in T2-T5
      treatments (no significance between 4 treatments). Epimedin A, B, icariin and
      total flavonoids contents were higher in T1 treatment, the lowest in T2
      treatment, those in T1 treatment was 41%, 62% and 27% higher than T2 treatment
      respectively (P<0.05). In a conclusion, E. pseudowushanense is a high nitrogen
      tolerant plant, 10.0 mmol*L-1 was the boundary point between growing general to
      well and the optimal nitrogen concentration for it was 10.0-13.0 mmol*L-1.
      Besides, it prefers to grow in NO-3 plus NH+4 and the optimal proportion was
      2.5?2.5.

PMID- 29376255
TI  - [Screening, identification and antimicrobial activity of alkaloid produced by
      endophytic actinomycetes from Fritillaria unibracteata in western Sichuan
      plateau].
AB  - To explore the resource of endophytic actinomycete in Fritillaria unibracteata,
      and alleviate the shortage of F. unibracteata resource, using F. unibracteata as
      experimental materials which growth in the western Sichuan plateau and cut its
      healthy bulb. Pure culture, insert, TLC and Oxford cup were applied to observe
      the mycelial morphology, research the ability of producing alkaloid and its
      antibacterial activity. Totally, 14 endophytic actinomycete strains were isolated
      by using Gao culture media. Based on the color reaction, 5 typical strains were
      selected for producing alkaloid. Through the TLC technique, all strains produced
      2 obvious alkaloids spots. Antibacterial activity determination showed that the
      antimicrobial effects of 2 strains is prominent, the diameter up to 11 mm.16S
      rRNA gene sequence comparison analysis showed that 5 strains belonging to the
      Streptomyces. The alkaloids produced by endophytic actinomycetes are not related
      to F. unibracteata, but its fermentation liquid has antibacterial effect, it is
      worthy of further study.

PMID- 29376256
TI  - [Identification of Cervus nippon, C.elaphus and their hybridize samples based on
      COI and SRY gene].
AB  - For rapid identification of Cervus nippon, C. elaphus and their hybridize
      samples, the specific PCR for mutual authentication of them was established based
      on the SNPs in COI and SRY sequence. C. nippon, C. elaphus and their hybridize
      samples were collected from different origins, total DNA of 24 identified samples
      were extracted, and the COI and SRY gene was seqenced. SNPs in the COI and SRY
      sequences of the samples were found by Clustul X 2.1 program. Primers for
      identifying C. nippon and C. elaphus were designed according to the SNP site, two
      multi-PCR reaction system were established to identify them. In addition, 24
      samples which were randomly collected in different herbal medicine market were
      identified. The band special for C. nippon (232 bp)and band special for C.
      elaphus (518 bp) based on COI sequence,and the band special for C. nippon (803
      bp)and band special for C. elaphus (425 bp) based on SRY sequence, were found
      using multi-PCR reaction, and three of the twenty-four samples were identified as
      the hybridize samples. The multi-PCR reaction system could be used to identify C.
      nippon, C. elaphus and their hybridize samples.

PMID- 29376257
TI  - [A study on identification of edible bird's nests by DNA barcodes].
AB  - To provide theoretical basis for the traceability and quality evaluation of
      edible bird's nests (EBNs), the Cytb sequence was applied to identify the origin
      of EBNs. A total of 39 experiment samples were collected from Malaysia,
      Indonesia, Vietnam and Thailand. Genomic DNA was extracted for the PCR reaction.
      The amplified products were sequenced. 36 sequences were downloaded from Gen Bank
      including edible nest swiftlet, black nest swiftlet, mascarene swiftlet, pacific
      swiftlet and germain's swiftlet. MEGA 7.0 was used to analyze the distinction of
      sequences by the method of calculating the distances in intraspecific and
      interspecific divergences and constructing NJ and UPMGA phylogenetic tree based
      on Kimera-2-parameter model. The results showed that 39 samples were from three
      kinds of EBNs. Interspecific divergences were significantly greater than the
      intraspecific one. Samples could be successfully distinguished by NJ and UPMGA
      phylogenetic tree. In conclusion, Cytb sequence could be used to distinguish the
      origin of EBNs and it is efficient for tracing the origin species of EBNs.

PMID- 29376258
TI  - [Exploring correlation between molecular state and nanofiltration mass transfer
      process of synephrine from Citrus aurantium].
AB  - Based on the solution-diffusion effect and the charge effect theory in
      nanofiltration separation, the correlation between initial concentration and mass
      transfer coefficient was constructed to establish a mathematic model of
      synephrine in mass transfer process and verify its applicability. The
      experimental results showed that there was a linear relationship between
      operation pressure and membrane flux. Meanwhile, the membrane flux was gradually
      decayed with the increase of solute concentration. Besides, mass transfer
      coefficient and initial concentration of synephrine showed power function
      correlation with each other by solution-diffusion effect and the charge effect,
      and the regression coefficients were greater than 0.9. The mass transfer
      coefficient of dissociation synephrine was less than that in the state of free
      and free-dissociation. Moreover, on the basis of power function relationship
      between mass transfer coefficient and initial concentration, the results showed
      that the predicted rejections of synephrine from Citrus aurantium water extract
      by use of the mathematical model approximated well to real ones, verifying that
      the model was practical and feasible. The unclear separation mechanism of
      nanofiltration for alkaloids was clarified preliminary by the predicted model of
      nanofiltration separation with synephrine as the example, providing theoretical
      and technical support for nanofiltration separation, especially for traditional
      Chinese medicine with alkaloids.

PMID- 29376259
TI  - [Protective effect of different polar fractions of Carbonized Rubiae Radix et
      Rhizoma (cRRR) against oxidative injury].
AB  - The protective effect of different polar fractions of Carbonized Rubiae Radix et
      Rhizoma (cRRR) against ox-LDL-induced damage to human umbilical vein endothelial
      cells (HUVECs) was investigated by MTT assay, and the components were identified
      by using UPLC-Q-TOF-MS. According to the study, ethyl acetate extract and n
      butanol extract could increase cell viability (P<0.01), while petroleum ether
      extract had no influence, and water extract could even inhibit the cell viability
      to some degree. Moreover, 32 compounds in four polar fractions were analyzed,
      including 31 quinones and their glycosides, and one rubiprasins C. Petroleum
      ether extract, ethyl acetate extract, n-butanol extract and water extract
      contained 23, 32, 26, 15 compounds, respectively. According to cell experiments
      in vitro, active fractions were ethyl acetate extract and n-butanol extract. The
      results could provide scientific references for further studies on effective
      material basic of cRRR, and lay a foundation for studies on the relationship
      between efficacies and materials.

PMID- 29376260
TI  - [Optimization of preparation procedures of tanshinone-IIA /beta-cyclodextrin
      inclusion complex and dissolution study of tanshinone-IIA in vitro].
AB  - In this paper, tanshinone-IIA (Tan-IIA)/beta-cyclodextrin (beta-CD) inclusion
      complexes were prepared by saturated aqueous solution method. Based on the single
      factor experiment, Box-Benhnken design and response surface method were utilized
      to optimize the preparation procedures of tanshinone-IIA/beta-cyclodextrin
      inclusion complexes. The ratio of beta-CD to Tan-IIA, experimental temperature
      and time were defined as independent variables, while the yield of the inclusion
      complexes, encapsulation efficiency and the generalized "normalized value" were
      set as the response value. In addition, the inclusion complexes were
      characterized by infrared spectroscopy (IR) and nuclear magnetic resonance (NMR).
      The results showed that optimum preparation conditions for Tan-IIA/beta-CD
      inclusion complex were as follows: Tan-IIA/beta-CD ratio of 1:7, the temperature
      of 48 C and the time of 3 h. Under the optimized conditions, the encapsulation
      efficiency of Tan-IIA/beta-CD inclusion complex was 84.75%. The Tan-IIA and beta
      CD inclusion complex can significantly improve the dissolution of Tan-IIA.

PMID- 29376262
TI  - [Nontargeted metabolomic analysis of Anoectochilus roxburghii at different
      cultivation stages].
AB  - Anoectochilus roxburghii is a traditional Chinese medicine and natural health
      products. In the modern cultivation system, A. roxburghii is micropropagated in
      tissue culture, and the plants are transferred to soil cultivation for months.
      However, it remains unclear about the necessity of soil cultivation for the
      accumulation of health beneficial compounds. In this paper, we performed
      nontargeted metabolomic analysis using GC-TOF-MS and UPLC-Q-TOF-MS, on A.
      roxburghii plants at tissue culture stage or after 3 months of soil cultivation.
      The results showed that the primary metabolites such as alcohols and organic
      acids are abundant in the tissue culture plants. In contrast, polysaccharide,
      nucleoside, esters and secondary metabolites such as flavonoids, terpenoids were
      significantly accumulated in cultivated seedlings. Flavonoids and polysaccharides
      are considered as the principle effective components in A. roxburghii. Soil
      cultivation period is therefore essential for the accumulation of these
      metabolites.

PMID- 29376263
TI  - [Interaction between gomizine D and alpha-glucosidase].
AB  - This paper describes a study exploring the interaction between gomizine D and
      alpha-glucosidase. The inhibitory activity of alpha-glucosidase by gomizine D was
      determined using PNPG as substrates Gomizine D gave the IC50 value of 0.59 mmol*L
      1, which was higher than that of acarbose (1.95 mmol*L-1). Gomizine D was a
      reversible and non-competitivealpha-glucosidase inhibitor with an inhibition
      constant Ki=4.026 g*L-1. The binding mode between gomizine D and alpha
      glucosidase was analyzed by AutoDock Vina molecular docking software. The lowest
      energy of Gomizine D binding to alpha-glucosidase was -7.7 kcal*mol-1, which was
      lower than that of acarbose (-6.6 kcal*mol-1). After binding with gomizine D, UV
      spectroscopy analysis displayed that the microenvironment of aromatic residue in
      the secondary structure of alpha-glucosidase was changed, and the polarity of
      protein was reduced.

PMID- 29376261
TI  - [A new sesquiterpene from Chinese agarwood induced by artificial holing].
AB  - In order to study the chemical constituents of n-butanol fraction of ethanol
      extract from Chinese agarwood induced by artificial holing, various
      chromatographic techniques were carried out to isolate compounds, and the
      structures of compounds were determined through a combined analysis of
      physicochemical properties and spectroscopic evidence. Seven compounds were
      obtained and identified as selina-3,11-dien-9,15-diol (1), aquilarone D (2),
      5alpha,6beta,7alpha,8beta-tetrahydroxy-2-[2-(2-hydroxyphenyl)ethyl]-5,6,7,8
      tetrahydrochromone (3), 6,7-dimethoxy-2-[2-(4-methoxyphenyl)ethyl]chromone (4),
      syringin (5), methyl (Z)-p-coumarate (6), and 4'-methoxycinnamic acid (7), among
      which compound 1 was a new compound and compounds 5-7 were isolated from agarwood
      for the first time. The bioactivity assay results concluded that compounds 6 and
      7 showed certain nematicidal activity against Panagrellus redivivus, and
      compounds 4, 6 and 7 exhibited cytotoxicity against BEL-7402, SGC-7901 and A549
      carcinoma cell lines.

PMID- 29376264
TI  - [Comparison of chemical constituents in different parts of Gardenia jasminoides
      based on multiple wavelength HPLC-DAD].
AB  - Seven compounds(deacetylasperulasidic acid methyl ester, gardenoside, chlorogenic
      acid, geniposide, crocin-I, crocin-II, chikusetsu saponin IVa)were determined
      simultaneously by multiple wavelength HPLC with diode array detector(DAD) in
      different parts of Gardenia jasminoides. The results showed that these components
      in different parts of G. jasminoides had a different distribution, and there was
      a large difference in content of each component. Geniposide was mainly
      distributed in fruits and leaves; chikusetsu saponin IVa was mainly distributed
      in roots and stems; crocus glycosides existed mainly in fruits; chlorogenic acid
      had a higher distribution in leaves and stems; gardenoside had a higher
      distribution in leaves and roots, while ceacetylasperulasidic acid methyl ester
      had a higher distribution in roots and stems. Based on the analysis of the
      chemical composition and content difference in different parts of G. jasminoides,
      the basis for the comprehensive utilization and quality evaluation of resources
      of G. jasminoides was provided.

PMID- 29376265
TI  - [Gegen Qinlian decoction activates PPARgamma to ameliorate adipocytic insulin
      resistance in diabetic SD rats and IR-3T3-L1 adipocytes].
AB  - To investigate the effects of Gegen Qinlian decoction(GQD) in improving
      adipocytic insulin resistance(IR) and explore its related molecular mechanism.
      Diabetic rats models were induced by high glucose and high-fat diet with a small
      dose of streptozotocin, and after GQD treatment for 3 months, blood biochemical
      indexes such as fasting blood-glucose(FBG), insulin, glycosylated serum
      protein(GSP) and HOMA-IRI were detected and assessed. After the total RNA was
      extracted from the adipose tissue of diabetic SD rats, PPARgamma, ADPN, GLUT4,
      GLUT2, ACACA and ACACB mRNA expression levels were separately detected by qPCR.
      Then, stable IR-3T3-L1 adipocyte model was built with 1 MUmol*L-1 dexamethasone.
      After the cell viability was detected by CCK-8 assay, 5%, 10% and 15% GQD
      containing serum(GQD-CS) were respectively used to treat IR-3T-L1 adipocytes for
      24 h. The contents of glucose, nonesterified fatty acid(NEFA) and adiponectin in
      cell culture supernatants were separately detected whereas the intracellular
      triglyceride(TG) contents of IR-3T3-L1 adipocytes were also measured. The ADPN,
      PPARgamma and GLUT4 mRNA and protein expression levels were respectively detected
      by qPCR and Western blot in IR-3T3-L1 adipocytes. Results showed that GQD
      significantly decreased fasting blood glucose, insulin and GSP(P<0.01), and down
      regulated HOMA-IRI(P<0.05) after the high-fat diet/streptozotocin-induced
      diabetic SD rats were treated for three months, with a good hypoglycemic effect.
      Moreover, PPARgamma, ADPN, GLUT4, GLUT2, ACACA and ACACB mRNA expression levels
      were significantly elevated in the adipose tissue of GQD-treated diabetic SD
      rats. The 5%, 10% and 15% GQD-CS significantly increased glucose consumption of
      IR-3T3-L1 adipocytes at 24 h treatment(P<0.01), significantly decreased the
      intracellular TG content (P<0.01), and down-regulated NEFA to a certain extent
      but not significantly. Moreover, GQD-CS significantly up-regulated GLUT4 and ADPN
      expression. The results indicated that GQD could activate PPARgamma to ameliorate
      adipocytic insulin resistance in the diabetic SD rats and IR-3T3-L1 adipocytes.

PMID- 29376266
TI  - [Effects of Pogostemon cablin on gastrointestinal function of rats with syndrome
      of damp retention in middle-jiao].
AB  - To investigate the effects of Pogostemon cablin(patchouli) on gastrointestinal
      function of rats with the syndrome of damp retention in middle-jiao, and explore
      its therapeutic mechanism. In this study, gastrointestinal function of rats with
      the syndrome of damp retention in middle-jiao was evaluated by multiple assays
      including gastric remnant rate, small intestine propelling rate, gastric juice
      quantity, pepsin activity and gastrointestinal tissue morphology. ELISA was used
      to detect gastrointestinal hormones including MTL, GAS, VIP and cytokines
      including TNF-alpha and interleukin 10 in rat serum. Real-time fluorescent
      quantitative PCR technique was used to detect relative mRNA expression of AQP3,
      AQP4 and AQP8 in gastric and colonic tissues to explore the mechanism of P.
      cablin in treatment of gastrointestinal functions. The results showed that middle
      and high dose of P. cablin (3.24, 6.48 g*kg-1) could obviously decrease the
      gastric remnant rate, promote gastric emptying, increase the small intestine
      propelling rate(P<0.05), speed up the propulsive movement of gastrointestinal
      tract, increase the secretion and acidity of gastric juice, increase the activity
      of pepsin, and improve the injury of gastrointestinal tissue. All the doses of P.
      cablin could increase the concentration of MTL and GAS in serum, reduce the
      concentration of VIP, TNF-alpha and IL-10 in serum, decrease the mRNA expression
      of AQP3 in gastric and colonic tissues, and increase the expression levels of
      AQP4 and AQP8 in colonic tissues. The regulatory effects were better in middle
      and high dose groups. In conclusion, regulation of the levels of gastrointestinal
      hormones, inflammatory cytokines and aquaporins may be the paths for P. cablin to
      maintain normal gastrointestinal function of rats with the syndrome of damp
      retention in middle-jiao. The results of the study laid a foundation for
      clarifying the treatment mechanism of aromatic damp-resolving drugs for
      indications including damp retention in middle-jiao and transformation failure of
      spleen.

PMID- 29376267
TI  - [Effect of saponins extracted from Panax japonicus on inhibiting cardiomyocyte
      apoptosis by AMPK/Sirt1/NF-kappaB signaling pathway in aging rats].
AB  - To investigate the effects of saponins extracted from Panax japonicus(SPJ) on
      cardiomyocyte apoptosis in natural aging rats and explore its underlying
      mechanisms. SD male rats were randomly divided into four groups: young control
      group, natural aging group, SPJ low dose group and SPJ high dose group, with 10
      rats in each group. The rats in natural aging group, SPJ low and high dose groups
      were respectively treated with normal saline, SPJ 10 and 60 mg*kg-1*d-1 from the
      beginning of 18 month-old, 6 days per week for 6 months till 24 month-old. Then
      the animals were sacrificed. Their myocardial morphology changes were observed by
      using haematoxylin-eoin(HE) staining; cardiomyocyte apoptosis was tested by using
      Tunel assays; and the protein expression levels of Bcl-2, Bax, IL-1beta, TNF
      alpha, AMPK, p-AMPK, Sirt1, and Ac-NF-kappaB p65 in myocardial tissues of rats
      were detected by Western blot. The results showed that SPJ could effectively
      improve the arrangement disorder of myocardial fibers, reduce the infiltration of
      inflammatory cells and inhibit cardiomyocyte apoptosis in natural aging rats. At
      the same time, SPJ could significantly inhibit the protein expression of Bax, IL
      1beta, TNF-alpha and Ac-NF-kappaB p65, and increase the expression of Bcl-2, Bcl
      2/Bax, p-AMPK/AMPK and Sirt1 in the heart tissues of natural aging rats. SPJ can
      effectively inhibit cardiomyocyte apoptosis in natural aging rats, and its
      mechanisms may be related with the regulation of inflammatory reaction by
      AMPK/Sirt1/NF-kappaB signaling pathway.

PMID- 29376268
TI  - [Effect of Chinese medicine of nourishing kidney and clearing liver on
      intermittent hypoxia induced injury model of HUVECs through p38MAPK/NF-kappaB
      signaling pathway].
AB  - This study aims to explore the intervention effect of Chinese medicine of
      nourishing kidney and clearing liver on intermittent hypoxia(IH) induced injury
      model of HUVECs through p38MAPK/NF-kappaB signaling pathway in vitro. HUVECs
      injury model was induced by modified IH treatment. The effective components of
      Chinese medicine of nourishing kidney and clearing liver including isochteroside,
      aucubin and ligustrazine were used as intervention drugs. The optimal
      compatibility concentration of them was screened in vitro, and then the optimal
      compatibility concentration was selected as the intervention dose to observe the
      effect on p38MAPK/NF-kappaB signaling pathway in IH induced injury model of
      HUVECs. The results showed that isochnae, aucubin and ligustrazine had the best
      anti-inflammatory effect at concentration of 0.01 mg*L-1. NF-kappaB p65 and p
      IkappaB in the nucleus in IH group were significantly higher than those in the
      normal control(N) group and the other groups. Immunofluorescence staining showed
      significant translocation of NF-kappaB p65 nucleus in IH group, and HUVECs
      adhesion capacity in IH group was increased significantly. As compared with IH
      group, the expression levels of p-p38MAPK, NF-kappaB p65 and p-IkappaB in p38MAPK
      inhibitor(INH) group and Chinese medicine of nourishing kidney and clearing
      liver(GDC) group were significantly decreased, and HUVECs adhesion capacity in
      INH group and GDC group was significantly inhibited as well. The optimal
      concentration of Chinese medicine of nourishing kidney and clearing liver can
      inhibit the phosphorylation of p38MAPK, and then inhibit the nuclear
      translocation and transcription function of NF-kappaB. This may be the mechanism
      of the protective effect of Chinese medicine on IH induced injury model of
      HUVECs.

PMID- 29376269
TI  - [Simultaneous determination of seven bioactive compounds and pharmacokinetics in
      rat plasma after oral administration of Yindan Xinnaotong Ruanjiaonang by UPLC
      MS/MS].
AB  - To estabish ultra-performance liquid chromatography-tandem mass spectrometry
      (UPLC-MS/MS) method for simultaneous determination of quercetin(QCT),
      isorhamnetin(ISR), kaempferol(KMF), ginkgolide A(GA), ginkgolide B(GB),
      ginkgolide C(GC) and bilobalide(BB) in rat plasma and investigate the
      pharmacokinetic process of seven compounds after oral administration of Yindan
      Xinnaotong Ruanjiaonang, The results indicated that all calibrations curves
      showed good linearity (r>=0.997 1). RSD of intra-day and inter-day precisions
      were all within 11%. The matrix effects and extraction recovery were in the range
      of 93.28%-103.6% and 72.43%-95.77% respectively. The peak concentration (Cmax) of
      QCT, ISR, KMF, GA, GB, GC and BB were (45.02+/-11.28), (49.90+/-13.82), (27.85+/
      8.38), (76.31+/-18.19), (76.54+/-15.43), (35.35+/-10.28), (48.70+/-12.34) MUg*L
      1, respectively. The peak time (tmax) of seven constituents were (0.33+/-0.11),
      (0.50+/-0.23), (0.33+/-0.14), (0.75+/-0.29), (1.0+/-0.35), (1.5+/-0.23), (0.75+/
      0.50) h, respectively. UPLC-MS/MS method established in this research was proved
      to be so rapid and sensitive that it can be applied to the pharmacokinetic study
      of seven bioactive constituents in Yindan Xinnaotong Ruanjiaonang.

PMID- 29376270
TI  - [Recognition and use of Aconitum carmichaeli from the pre-Qin period to Tang
      Dynasty-Also on rules in evolution of traditional Chinese medicine].
AB  - The recognition and use of Aconitum carmichaeli have undergone various changes
      from the pre-Qin period to Tang dynasty. From "the drug of evil" to "the leader
      of hundreds of medicine ", people's understanding of A. carmichaeli is more and
      more deep and specific. The medicinal values of A. Carmichaeli have been
      excavated, and it is widely used in brewing skill, agricultural production,
      Taoism, Buddhism and festival customs. Its function is becoming more and more
      diversified and routinized. By studying it, we can glimpse some rules in the
      evolution of traditional Chinese medicine, for instance relationships between
      drugs and poisons, drugs and non-drug; the inheritance and integration of medical
      books' recording; the generalization and routinization of Chinese medicinal
      medicines' functions, and so on.

PMID- 29376271
TI  - [China's contribution to research and development of antiparasitic products -
      Inspiration from Nobel Prize in Physiology or Medicine 2015].
AB  - Chinese scientist Tu You-you won the Nobel Prize in Physiology or Medicine 2015,
      due to her outstanding contribution to the discovery of antimalarial drug
      artemisinin. The discovery of artemisinin is a great breakthrough using modern
      pharmaceutical technology to excavate ancient Chinese traditional medicine
      resources, based on government's coordination mechanisms. This article analyzes
      the research and development status of the current global antiparasitic products,
      as well as China's needs and strengths in related areas. The authors propose that
      China should take the advantage of government financing and research capacity to
      strengthen the research and development of antiparasitic products, so as to
      contribute more to improving global health equity.

PMID- 29376272
TI  - [Surveillance and risk assessment system of schistosomiasis in Jiangsu Province
      III Risk of schistosomiasis transmission in the area along the Yangtze River in
      Yangzhou City].
AB  - OBJECTIVE: To evaluate the potential risk of schistosomiasis transmission in the
      area along the Yangtze River in Yangzhou City, so as to provide evidences for
      establishing a post-transmission surveillance system for schistosomiasis in
      marshland regions. METHODS: The water infectivity, floating boatmen and fishermen
      infection, reservoir host infection and wild feces contamination were
      investigated in five districts/counties along the Yangtze River in Yangzhou City,
      including Guangling, Hanjiang, Jiangdu, Yizheng and Development Zone, and the
      transmission factors and risky characteristics were assessed after interruption
      of schistosomiasis transmission in marshland regions. RESULTS: A total of 15 key
      water regions were identified in the area along the Yangtze River in Yangzhou
      City in 2015. A total of 1 500 sentinel mice were placed, after breeding, their
      overall survival rate was 99.33%; 1 490 were dissected, with no schistosome
      infection. Of the 5 576 floating boatmen and fishermen examined, no schistosome
      infection was observed, and among the 3 566 domestic animals (including 171
      cattle, 1 895 sheep and 1 500 pigs), no infections were detected. During the
      period between January and March, 2016, there were 3 200 mouse traps placed on 8
      marshlands, and 62 wild mice were captured from 6 marshlands, with a capture rate
      of 1.94%, and no schistosomeinfected wild mice were seen. In addition, there were
      35 pieces of fresh wild feces captured from 7 marshlands, including 11 pieces of
      bovine feces (31.43%), 17 pieces of sheep feces (48.57%), 2 pieces of dog feces
      (5.71%) and 5 pieces of other feces (14.29%), and no infections were detected.
      CONCLUSIONS: There is a low risk of schistosomiasis transmission in the area
      along the Yangtze River in Yangzhou City. However, the contamination of feces
      from bovine and sheep that are freely pastured on marshlands is a big threat to
      schistosomiasis control.

PMID- 29376273
TI  - [Epidemiological investigation on confirmed cases of schistosomiasis in Hubei
      Province].
AB  - OBJECTIVE: To grasp the distribution and epidemiology of confirmed cases of
      schistosomiasis in Hubei Province, so as to provide the evidence for promoting
      the prevention and control work. METHODS: The confirmed cases of schistosomiasis
      in Hubei Province from 2010 to 2014 were epidemiologically investigated, and the
      prevalence characteristics and main influencing factors were analyzed. RESULTS: A
      total of 10 102 confirmed cases from 2010 to 2014 were surveyed. There were 1 062
      local infected patients, accounting for 10.51% and including 354 repeated
      infections and 17 newly infected. There were 290 foreigninfected patients,
      accounting for 2.87%, with 206 repeated infection cases and 84 newly infected.
      There were 8 750 historical patients, including 2 229 patients who leaked the
      former schistosomiasis investigations, accounting for 22.06%; 570 patients missed
      treatment, accounting for 5.64%; 3 640 patients were treated with non-standard
      therapy, accounting for 36.03%; 2 311 patients were treated with poor medication
      efficacy, accounting for 22.88%. The multivariate non-conditional Logistic
      regression, targeting at confirmed cases in 2014, showed that, for the leaking
      investigations, the potential risk factors included the age, educational level,
      and latrine renovation (b>0, OR>1), the protective factors were the times of
      previous treatment, cattle feeding in villager team, and Oncomelania hupensis
      snails in surroundings (b<0, OR<1); for the treatment-missing, the age,
      educational level, snails in the surroundings of residence were risk factors
      (b<0, OR<1); for the substandard treatment, the risk factors included the
      occupation and snails in the surroundings of residence (b>0, OR>1), and the
      educational level and snails in the own field were protective factors (b<0,
      OR<1). CONCLUSIONS: The epidemiological investigation on the confirmed cases of
      schistosomiasis could grasp the epidemic factors so as to improve the management
      and carry out the scientific control.

PMID- 29376274
TI  - [Investigation of direct medical expense for surgical patients with splenomegalic
      advanced schistosomiasis in Hunan Province from 2010 to 2014].
AB  - OBJECTIVE: To understand the direct medical expense for surgical patients with
      splenomegalic advanced schistosomiasis and its influencing factors, so as to
      provide evidences for relevant departments to improve the rescue strategy of
      advanced schistosomiasis. METHODS: The data about the expenses of patients with
      splenomegalic advanced schistosomiasis hospitalized in Xiangyue Hospital
      affiliated to Hunan Institute of Schistosomiasis Control from January 2010 to
      August 2014 were collected, the hospitalization expense and hospital stays of the
      patients were analyzed, and the factors influencing the hospital expenses were
      analyzed by the univariate and multi-factor analyses. RESULTS: From January 2010
      to August 2014, totally 249 cases were hospitalized in the hospital, their
      average hospital stays and hospital expenses were 28.92 d and 18 896.13 Yuan, and
      both of them were increased year by year. Among all the kinds of expenses, the
      constitution ratios of the medicine expenses were the highest, and those in the 5
      years were all above 44%. The results of the univariate and multi-factor analyses
      showed that the hospital stays, the amount of intraoperative bleeding, liver
      function classification, postoperative complications, age, portal hypertensive
      gastropathy were the influencing factors of the hospital expenses. CONCLUSIONS:
      Presently, the burden of the direct hospital expenses of the patients with
      splenomegalic advanced schistosomiasis is still heavy. The government should
      further improve the proportion of the compensation of medical assistance and
      perfect the medical aid scheme. Meanwhile, the hospitals should strengthen the
      management and standardize medical behavior to reduce the hospitalization
      expenses of the patients.

PMID- 29376275
TI  - [Effect of two-level community-based health education pattern on schistosomiasis
      control].
AB  - OBJECTIVE: To implement a two-level community-based health education pattern of
      schistosomiasis in residents of endemic areas in marshland and lake regions, so
      as to explore the suitable pattern of health education under hypo-endemic
      situation. METHODS: Two schistosomiasis endemic villages in Jiangling County,
      Hubei Province were collected as study areas, and among which, one village was
      treated as an intervention group, where the two-level community-based health
      education pattern as well as regular control measures was implemented; the other
      village was a control group, where only regular control measures were
      implemented. The awareness rates on schistosomiasis control, the rates of correct
      behavior and the compliance rates of examination, treatment and chemotherapy of
      the two groups before and after the intervention were compared. RESULTS:
      According to the results of the baseline survey in 2014, the awareness rates of
      schistosomiasis control of the intervention and control groups were 84.00% and
      77.45%, respectively, the correct rates of behavior of the two groups were 72.00%
      and 63.73%, respectively, and the compliance rates of the treatment were 80.36%
      and 82.28%, respectively, there were no statistically significant differences
      between all the above rates of the two groups (all P > 0.05). After the
      intervention of the two-level community-based health education, the correct rates
      of behavior, and the compliance rates of examination and chemotherapy of the two
      groups were 92.31% and 80.37%, 95.11% and 82.55%, 84.13% and 63.64%,
      respectively, and the differences between all the rates above of the two groups
      were statistically significant (all P < 0.05). When compared to those before
      intervention, the growing rates of the compliance rates of examination, treatment
      and chemotherapy of the intervention group were 20.97%, 15.33% and 23.29%,
      respectively, while those of control group were 14.27%, 4.17%, -3.77%,
      respectively, the growing rates of the intervention groups were higher than those
      of the control groups. CONCLUSIONS: Through the two-level community-based pattern
      of health education, the compliance rates of examination and treatment of the
      residents have improved, and therefore, the pattern is suitable for
      popularization and application in marshland and lake regions.

PMID- 29376276
TI  - [Study on value of IHA in diagnosis of schistosomiasis japonica].
AB  - OBJECTIVE: To evaluate the value of indirect hemagglutination test (IHA) in
      schistosomiasis diagnosis. METHODS: The literature concerned schistosomiasis
      diagnosis with IHA in the databases of Medline, CNKI, VIP and Wanfang Data from
      1982 to 2014 was collected and evaluated. RESULTS: Totally 21 articles which were
      satisfied with the research criteria were analyzed with the Meta-analysis method.
      The IHA method had high value in schistosomiasis diagnosis, the AUCSROC of IHA in
      laboratory evaluation was 0.990 6, while in filed evaluation was 0.832 9, and the
      difference between them was significant (Z = 4.50, P < 0.05). CONCLUSIONS: The
      diagnosis value of IHA in field evaluation is less than that in laboratory. In
      the process of the elimination of schistosomiasis, developing a new and higher
      sensitive reagent in schistosomiasis diagnosis is needed.

PMID- 29376277
TI  - [Molecular structure and alternative splicing analysis of heat shock factors of
      Schistosoma japonicum].
AB  - OBJECTIVE: To clone and identify the heat shock factors (HSFs) of Schistosoma
      japonicum and analyze its molecular structure and alternative splicing pattern.
      METHODS: The New Zealand rabbits were infected with the cercariae of Schistosoma
      japonicum and were killed and dissected 42 days post-infection, and the adult
      worms of S. japonicum and the livers of the rabbits were harvested. Then, the
      total RNA was extracted by using Trizol reagent. The Sj-hsf open reading frame
      (ORF) and the alternative splicing fragments were amplified by RT-PCR from the
      female, male and egg samples, then cloned and verified by enzyme digestion and
      sequencing. DNAMAN 8.0, InterPro, Mega 6 combined with the Internet databases
      were utilized to clarify the gene structure, functional domains, alternative
      splicing pattern, and the homology and phylogenetic tree of HSFs. RESULTS: Sj-hsf
      ORF and the alternative splicing fragments were amplified from the female, male
      and egg samples of S. japonicum by RT-PCR. After cloning, the positive
      recombinant plasmids pBSjHSFf-F, pBSjHSFf-M, pBSjHSFf-E containing Sj-hsf ORF,
      pBSjHSFs-F, pBSjHSFs-M, pBSjHSFs-E with Sj-hsf alternative splicing fragments
      were identified by enzyme digestion and sequencing. Three alternative splicing Sj
      hsf isoforms were observed through sequence analysis: Sj-hsf-isoform1 (2 050 bp),
      Sj-hsf -isoform2 (2 086 bp) and Sj - hsf -isoform3 (2 111 bp); the GenBank
      accession numbers were KU954546, KX119143 and KX119144, respectively. All the
      three isoforms located in the same Contig SJC_S000780 of S. japonicum genome and
      all expressed at female, male and egg stages, but Sj-hsf-isoform1 with a high
      level expression. Sj-HSF-isoform1 (671 aa) and Sj-HSF-isoform2 (683 aa) had DBD
      (DNA binding domain), HR-A/B and HR-C domains, while Sj-HSF-isoform3 (282 aa)
      stopped in advance without HR-C domain. Phylogenetic tree analysis of HSFs
      illustrated that Sj - HSFs belonged to HSF1 family, with a close phylogenetic
      relationship to Sm-HSFs. CONCLUSIONS: There are three alternative splicing
      isoforms of Sj-HSF existing in the female, male and egg stages of S. japonicum,
      but Sj-HSF-isoform1 expresses in a high-level. This study lays the foundation for
      further study on molecular mechanisms of Sj-HSFs in regulating the heat shock
      response system.

PMID- 29376278
TI  - [Enzyme kinetic analysis of Oncomelania hupensis exposed to active ingredient of
      Buddleja lindleyana (AIBL)].
AB  - OBJECTIVE: To analyze the enzyme kinetics of active ingredient of Buddleja
      lindleyana (AIBL) against Oncomelania hupensis, the intermediate host of
      Schistosoma japonicum. METHODS: O. hupensis snails were placed in 1 000 ml of
      3.55 mg/L AIBL solution for 24, 48 h and 72 h, respectively, and the enzyme
      kinetics of alanine aminotransferase (GPT) was determined by Reitman-Frankel
      assay, lactate dehydrogenase (LDH) by the chemical inhibition lactic acid
      substrate method, alkaline phosphatase (AKP) by the disodium phenyl phosphate
      colorimetric method, acetylcholine esterase (AChE) and malate dehydrogenas (MDH)
      by ELISA, and succinate dehydrogenase (SDH) by the phenazine methyl sulfate
      reaction method (PMS) in the soft tissues of O. hupensis before and after AIBL
      treatment. RESULTS: Following exposure to 3.55 mg/L AIBL solution for 24 h, the
      GPT, LDH, and AKP activities significantly improved in the soft tissues of O.
      hupensis, while the SDH and MDH activities were significantly lowered in the head
      foot and liver. However, AIBL treatment did not cause significant effect on AChE
      activity in O. hupensis. CONCLUSIONS: AIBL causes significant damages to O.
      hupensis liver and can efficiently act on anaerobic and aerobic respiration loci,
      which will hinder energy metabolism, and cause inadequate energy supply in cells
      used for normal secretion, eventually leading to O. hupensis death.

PMID- 29376279
TI  - [Analysis of malaria epidemic situation and control in Hubei Province from 1974
      to 2015].
AB  - OBJECTIVE: To analyze the malaria control measures and epidemic trend in Hubei
      Province from 1974 to 2015, so as to provide the evidence for malaria elimination
      path analysis. METHODS: The malaria control data in Hubei Province from 1974 to
      2015 were collected and analyzed retrospectively by descriptive epidemiological
      methods. RESULTS: The epidemic process of malaria in Hubei Province was divided
      into four stages. From 1974 to 1979, it was high prevalence state of malaria, and
      the average annual incidence was 174.47/10 000. From 1980 to 1999, the main
      control strategies were to control the infection source and mosquitoes, and the
      average annual incidence was 17.30/10 000, significantly downward. From 2000 to
      2009, through the surveillance of infection sources and controlling malaria
      outbreaks and strengthening the floating population management, the average
      annual incidence was 0.42/10 000. After 2010, followed by the elimination phase
      of malaria, the incidence continued to decline. In 2013, there was no local
      infection for the first time. The difference of average annual incidence among
      above-mentioned stages was statistically significant (chi2 = 1 254.36, P < 0.05).
      CONCLUSIONS: The malaria epidemic process in Hubei Provincial experienced the
      high epidemic stage, sharply drop stage, low incidence phase and the elimination
      phase. However, the natural factors affecting malaria still exist. Therefore,
      strengthening the control of imported malaria and surveillance should be the main
      task in the process of eliminating malaria in the future.

PMID- 29376280
TI  - [Epidemiological analysis of malaria prevalence in Sichuan Province, 2012-2014].
AB  - OBJECTIVE: To understand the characteristics of malaria prevalence in Sichuan
      Province from 2012 to 2014, so as to provide evidences for improving the work of
      malaria elimination. METHODS: The epidemiological data of malaria cases in
      Sichuan Province were collected from the Disease Surveillance Information
      Reporting System of Chinese Center for Disease Control and Prevention, and
      analyzed with the descriptive epidemiological method. RESULTS: A total of 690
      imported malaria cases were reported in Sichuan Province from 2012 to 2014. In
      detail, 54.49% (376/690) were falciparum malaria cases, 42.03% (290/690) were
      vivax malaria cases, 0.58% (4/690) were malariae malaria cases, 1.88% (13/690)
      were ovale malaria cases, and 1.01% (7/690) were mixed infection cases with
      Plasmodium vivax and P. falciparum. Among them, five cases died. Totally 671
      malaria cases were infected overseas, accounting for 97.25% of the total cases.
      Among which, 517 patients returned from Africa and 138 patients returned from
      Southeast Asia. There were malaria cases reported in the whole year, and 185
      cases were reported in May and June, accounting for 26.81% of the total cases.
      The cases distributed in 20 prefecture-level cities in the whole province, and
      there were 137 and 105 ones reported in Guangan and Chengdu, respectively, which
      accounted for 35.07% of the total cases. CONCLUSIONS: The number of patients with
      overseas imported malaria in Sichuan Province increases year by year, and
      therefore effective measures should be carried out to control the overseas
      imported malaria.

PMID- 29376281
TI  - [Analysis of highly cited papers related to malaria in Chinese journals from 2006
      to 2013].
AB  - OBJECTIVE: To analyze the highly cited malaria papers published in Chinese
      journals from 2006 to 2013, so as to provide the evidence for formulating the
      plan of selecting topics to the journal editors. METHODS: The published articles
      related to malaria included in CNKI and Wanfang medical network from 2006 to 2013
      were collected, and the highly cited papers were selected according to the
      citation frequency calculated by Price's formula. Then the characteristics of the
      highly cited papers were analyzed. RESULTS: From 2006 to 2013, a total of 1 976
      published papers related to malaria were searched in Chinese journals and 98
      papers of them were selected as highly cited papers. In the highly cited papers,
      18 papers were published in China Tropical Medicine, and 16 and 15 papers were
      published in Chinese Journal of Parasitology and Parasitic Diseases and Chinese
      Journal of Schistosomiasis Control, respectively; and original articles accounted
      for 42.86%; the first authors of these papers were from 44 institutions, and
      40.91% of them were from centers for disease control and prevention (CDCs); a
      percentage of 22.45% of the highly cited papers received fund programs, and most
      of them were national or provincial funds. The research hotspots were focused on
      the epidemiology and control, and epidemic situation of malaria. CONCLUSIONS: The
      highly cited papers related to malaria are mainly from CDCs and research
      institutions, and the related journals could use this information to chose topics
      and solicit contributions to improve their influence.

PMID- 29376283
TI  - [Analysis of polymorphism of Pfhrp2 gene in Plasmodium falciparum from falciparum
      malaria patients in Yunnan Province].
AB  - OBJECTIVE: To analyze the polymorphism of histidine rich protein 2 (HRP II) gene
      in Plasmodium falciparum (Pfhrp2) from falciparum malaria patients in Yunnan
      Province, so as to lay the foundation for studying the defection of antigen genes
      of Plasmodium. METHODS: The filter paper blood samples and related information of
      falciparum malaria cases reported were obtained in Yunnan Province from August
      2012 to September 2015. Under the guidance of the specific primers, the exon2
      regions in Pfhrp2 gene in P. falciparum from DNA samples were amplified by PCR,
      and the PCR products were sequenced. The sequences of exon2 region in Pfhrp2 gene
      were blasted by comparing with the reference sequences AY816237, AY816240, and
      AY816301. Next, the polymorphism of the sequence in exon2 region of Pfhrp2 gene
      was analyzed by MEGA 5.04 software. The conserved sites and genetic distances
      between sequences were calculated by using the software as well, and the
      clustering tree was drawn according to the genetic distances between the amino
      acid sequences. RESULTS: A total of 218 bloods samples from the falciparum
      malaria cases in 15 prefectures of Yunnan Province were collected, and the
      sources of infection included Yunnan, Africa and Myanmar. The PCR results showed
      that the exon2 regions in Pfhrp2 genes of 155 samples were positive by
      amplification and their products were sequenced successfully. The sequence
      analysis showed that the length range of the amino acid residues of exon2 region
      in Pfhrp2 gene was from 115 aa to 298 aa, the average length was 239.7 aa. There
      was no statistically significance among the means of the amino acid residues of
      the isolates from Africa (239.9 aa), Myanmar (239.5 aa) and Yunnan (241.6 aa) (F
      = 0.025, P > 0.05). All the 155 amino acid sequences ended with type 12 repeat,
      98.1% (152/155) of them started with type 1 repeat and 1.9% (3/155) of them
      started with type 2. Type 2 presented most frequently repeat in all the sequences
      and the average repeat times were 12.9. The homologous locus of the DNA sequences
      in exon2 regions of the 155 Pfhrp2 genes was 894 bp, among which the conservative
      sites accounted for 20.6% (186/894), and the variable sites for 78.2% (699/ 894).
      The genetic distances between the sequences of Africa isolates ranged from 0 to
      0.741, and those of the Myanmar and Yunnan isolates were 0-0.948 and 0-0.750,
      respectively. The cluster analysis showed that all the 155 sequences clustered
      into 3 categories on genetic distances between amino acid sequences according to
      the size of the amino acid sequence length. At the same level, the sequences had
      approximate lengths and amino acid repeat types. CONCLUSIONS: The sequence of
      exon2 region in Pfhrp2 gene of P. falciparum from falciparum malaria cases in
      Yunnan Province is highly polymorphic, the P. falciparum isolates are clustered
      mainly according to the size of the amino acid sequence of exon2 region in Pfhrp2
      gene.

PMID- 29376282
TI  - [Multiple insecticide resistances and kdr mutation of Culex pipiens pallens in
      north-central Anhui Province].
AB  - OBJECTIVE: To understand the status of resistance to multiple insecticides and
      the frequencies of kdr mutations in Culex pipiens pallens from north-central
      Anhui Province. METHODS: From July to September, 2014, the C. pipiens pallens
      mosquito larvae were collected in Huaibei, Bengbu and Chuzhou cities of the north
      central Anhui Province and reared to adults. The female adult mosquitoes at 3-5
      days post emergence were tested for susceptibility to the four insecticides,
      namely 0.05% deltamethrin, 5% malathion, 0.1% bendiocarb and 4% DDT, by using the
      standard WHO resistance tube bioassay. The detection of the point mutations of
      the kdr gene at codon 1014 was conducted by PCR and DNA sequencing in the
      deltamethrin-resistant and -susceptible mosquitoes. RESULTS: High levels of
      resistance to all the four insecticides were found in all the three tested
      populations, although mosquito mortality varied among populations and test
      insecticides. Among the test insecticides, DDT showed lowest mortality with no
      significant difference (F = 1.027, P > 0.05) in all test populations, whereas
      significantly different mortalities were observed among populations for the
      remained three insecticides tested (deltamethrin, malathion, and bendiocarb) (F =
      23.823, 33.955, 128.841; all P < 0.01). Two types of non-synonymous kdr mutation
      at codon position 1014 (L1014F and L1014S) were observed. A positive correlation
      between L1014F mutation frequencies and deltamethrin resistance levels were
      detected in the three mosquito populations (r2 = 0.718, P < 0.01). CONCLUSIONS:
      The observed high levels of resistance to multiple-insecticides coupled with the
      occurrence of medium to high kdr frequencies in populations of C. pipiens pallens
      could profoundly affect the mosquito vector control programme in China. The local
      health departments need to strengthen vector dynamic monitoring and implement
      rational resistance management strategies.

PMID- 29376284
TI  - [Investigation on epidemic foci of paragonimiasis in eastern part of Zhenghe
      County, Fujian Province].
AB  - OBJECTIVE: To investigate the species and hosts of Paragonimus and its infection
      rate in eastern part of Zhenghe County, Fujian Province, so as to determine the
      local foci of Paragonimus. METHODS: The snails, crabs and stools of wild cats
      were collected for the examinations of cercariae, metacercariae and eggs of
      Paragonimus. The geographical and environmental conditions of the areas were also
      investigated. RESULTS: A total of 4 890 Pseudobythinella jianouensis snails and 1
      035 Semisulcospira liberlina snails were examined, and the cercariae of
      Paragonimus were only found in P. jianouensis, with an infection rate of 0.10%
      (5/4 890). Bottapotamon zhengheensis sp. nov. as the second intermediate host of
      P. skrjabini, were examined, and the infection rate was 85.29% (29/34) and the
      average numbers of metacercariae per crab and per gram of crab tissues were 3.85
      and 0.62, respectively. Thirty-six Sinopotamun fujianensis crabs, as the second
      intermediate host of P. westermani, were examined, and the infection rate was
      38.89% (14/36) and the average numbers of metacercariae per crab and per gram of
      crab tissues were 6.43 and 0.03, respectively. The eggs of Paragonimus were
      detected in 1 of 2 muck specimens of wild cats. CONCLUSIONS: The data suggest
      that there is a focus of middle-to-high level of infection caused by P.
      westermani and P. skrjabini in the eastern part of Zhenghe County.

PMID- 29376285
TI  - [Population dynamics and spatial distribution pattern of Aleuroglyphus ovatus].
AB  - OBJECTIVE: To characterize the population dynamics and spatial distribution of
      Aleuroglyphus ovatus in the flour warehouse, so as to provide the basic evidence
      for improving the sampling guidelines that are essential for effective pest
      monitoring and management. METHODS: The samples from flour warehouses of four
      localities were collected, examined and counted for A. ovatus in every month in
      Wuhu City. The dispersion pattern target, Iwao m*/x regression analysis and
      Taylor power method were used for analyzing the spatial distribution pattern of
      A. ovatus in the flour warehouses. RESULTS: The peaks of population dynamics of
      A. ovatus were discovered in July and September, respectively. The indexes of
      dispersion were as follows:I > 0, CA > 0, m*/x > 1. At the same time, the
      parameters in the equation of Iwao:m*=5.471+1.022 x (r = 0.999) and Taylor: lgS2
      = 0.697+1.111 lg x (r = 0.987) showed that the spatial distribution pattern of A.
      ovatus was assembled. CONCLUSIONS: The peaks of population dynamics of A. ovatus
      in the flour warehouse are bimodal pattern, and the spatial distribution pattern
      of A. ovatus is assembled.

PMID- 29376287
TI  - [Investigation on Cheyletoidea mites breeding in culture environment of
      Eupolyphaga sinensis and morphologic observation of Eucheyletia reticulate
      Cunliffe].
AB  - OBJECTIVE: To investigate the species of Cheyletoidea mites breeding in the
      culture environment of Eupolyphaga sinensis and to observe the morphology of
      Eucheyletia reticulata Cunliffe. METHODS: The soil samples from an E. sinensis
      farm in northern Anhui were collected. The mites in the soil samples were
      separated directly under a microscope and the glass specimens were made to
      observe the morphological feature of the mites under a light microscope, then the
      mites species were identified and classified based on the morphological
      characteristics. RESULTS: In the culture soil of E. sinensis, totally 7 kinds of
      Cheyletoidea mites were isolated, namely Eucheyletia reticulata Cunliffe,
      Cheyletus eruditus Schrank, Cheyletus malaccensis Oudemans, Cheyletus troussarti
      Oudemans, Cheyletus aveisor Rohdendorz, Acaropsis sollers Rohdendorz and
      Cheletomorpha lepidopterorum Shaw. They belonged to genera Eucheyletia,
      Cheletomorpha, Acaropsis and Cheyletus of Cheyletidae Leach family. The
      Eucheyletia reticulata Cunliffe was firstly found in the culture environment of
      E. sinensis, and its gnathosoma was large, the pedipalpal femurs were expanding
      and there were two strips of comb hair and two smooth bristles on the pedipalpal
      tarsus, and the back of the body was covered with two pieces of tergum, which
      were decorated with reticular pattern. The body and foot setae were fan-shape.
      CONCLUSIONS: There are various of Cheyletoidea mites found in the breeding
      environment of E. sinensis. These mites are important species for pest control in
      the culture environments of E. sinensis. Related measures should be taken to
      prevent the excessive growth of Cheyletoidea mites, so as to avoid the adverse
      effects on the quality and quantity of E. sinensis.

PMID- 29376286
TI  - [Analysis of soil components along water channel of east route of South-to-North
      Water Diversion Project].
AB  - OBJECTIVE: To explore the relationship between the soil components along the
      areas of the east route of the Southto-North Water Diversion Project and the
      survival situation of Oncomelania hupensis snails. METHODS: Four study sites were
      selected along the project, and soil samples were collected to analyze the
      components. The amounts of components among the different study sites were
      compared statistically. RESULTS: Except zinc, sodium, and phosphorus, the
      contents of the soil components where the snails survived were different from
      those where snails were dead (t = -19.150 to 12.810, all P < 0.01). However, the
      logistic regression analysis did not obtain a model with statistical
      significance. CONCLUSIONS: O. hupensis snails live in the soil with adequate
      organic matter and neutral pH value. Along with the global warming and the
      operation of the South-toNorth Water Diversion Project, O. hupensis snails may
      survive in the northern area, and therefore, the surveillance work should be
      strengthened.

PMID- 29376288
TI  - [Risk factors of Schistosoma japonicum infection in Xingzi County].
AB  - OBJECTIVE: To explore the risk factors of Schistosoma japonicum infection in the
      residents in Xingzi County, Jiangxi Province. METHODS: Six administrative
      villages from different areas were randomly selected by the cluster sampling
      method as the study sites in Xingzi Country in 2013, and all the residents aged 5
      years or above were investigated epidemiologically, and the schistosome infection
      was surveyed by Kato-Katz technique. The risk factors of schistosomiasis were
      analyzed by using the Chi-square test analysis and multivariate Logistic
      regression model. RESULTS: In 2013, there were 2 050 residents received the stool
      examination and 146 persons were positive, the schistosome infection rate was
      7.1%. The Chi-square test showed that gender, age, occupation and education level
      were associated with the population infection rate (chi2 = 26.485,16.836,25.700,
      90.805, all P < 0.05). The multivariate Logistic regression mode showed that the
      probability of schistosomiasis for the male was 3.041 times as much as that for
      the female; the probability of schistosomiasis for the illiteracy and primary
      education level crowd was 8.870 times as much as that for the college degree or
      above crowed; the probability of schistosomiasis for the junior middle school
      education level crowd was 5.598 times as much as that for the college degree or
      above crowed; the probability of schistosomiasis for the high school education
      level crowd was 2.995 times as much as that for the college degree or above
      crowed; the probability of infection of fishermen was the highest, which was
      3.053 times as much as that for the other professional crowds. CONCLUSIONS: The
      risk factors of schistosome infection mainly include gender, occupation and the
      education level. We should strengthen the health education of schistosomiasis
      control, protection against the infested water contact, and so on.

PMID- 29376289
TI  - [Surveillance of schistosomiasis in Hubei Province in 2014].
AB  - OBJECTIVE: To analyze the surveillance results of schistosomiasis and understand
      the transmission situation in Hubei Province in 2014. METHODS: According to the
      Scheme of Schistosomiasis Surveillance in Hubei Province (the 2009 edition), 207
      endemic sites were selected, where the schistosome infections of residents and
      livestock, and the distribution of Oncomelania hupensis snails were investigated.
      RESULTS: In the 207 sites, there were 27 sites without positive results of the
      blood tests and 129 sites without positive results of the stool tests. The
      infection rates of residents and cattle were 0.17% and 0, respectively. The
      density of living snails was 0.339 3 snails/0.1m2, the rate of living snails was
      10.12%, and the infection rate of snails was 0. The infection rate of residents
      in the inner embankment type was 0.22%, higher than the rates in the other types.
      In different age groups, the infection rate in the 50-59 years age group was
      higher than the rates in other age groups. The infection rates of residents in
      farmer and fisherman were higher than those in the other occupation groups. The
      infection rate of floating people was 0, and no acute schistosomiasis patients
      were found. CONCLUSIONS: The endemic situation of schistosomiasis has decreased
      obviously in Hubei Province, and the whole province has achieved the criteria for
      transmission control of schistosomiasis.

PMID- 29376290
TI  - [Analysis of malaria epidemic situation in Changzhou City from 2010 to 2014].
AB  - OBJECTIVE: To grasp the malaria epidemic situation in Changzhou City from 2010 to
      2014, so as to provide the evidence for formulating and adjusting malaria control
      strategies and measures. METHODS: The epidemiological data of malaria cases in
      the special report system from 2010 to 2014 were collected, and the malaria
      epidemic situation and the diagnosis and treatment of malaria patients were
      analyzed. RESULTS: There were 132 malaria cases reported in Changzhou City from
      2010 to 2014, with a decrease of 27.47% compared to 182 cases from 2005 to 2009.
      Among the 132 cases, 2 cases were local infected cases and the remaining 130
      cases were imported cases. Four cases were clinically diagnosed and 128 cases
      were laboratory confirmed, with 97 cases of malignant malaria, 14 cases of vivax
      malaria, 13 cases of ovale malaria, and 4 cases of quartan malaria. The 132 cases
      were distributed in five districts:56 cases in Jintan City, 51 cases in Liyang
      City, 19 cases in Tianning District, 3 cases in Wujin District, and 3 cases in
      Xinbei District. The median duration between the onset and treatment of the
      disease was 2 days, and the median duration between the diagnosis and treatment
      was 1 day. The diagnosing units were concentrated on the county-level disease
      control agencies, and medical institutions at county and municipal levels,
      accounting for 92.42% (122/132). From 2011 to 2014, there were no local malaria
      cases. CONCLUSIONS: From 2012 to 2014, there have been no local malaria cases in
      Changzhou City, and the goal of eliminating malaria has been achieved basically.
      However, there are still many imported malaria cases, and the infected species
      are diverse. Therefore, imported malaria is still the key of malaria prevention
      and control.

PMID- 29376291
TI  - [Investigation and analysis of overseas imported malaria prevalence in Henan
      Province from 2012 to 2014].
AB  - OBJECTIVE: To understand the epidemic characteristics of imported malaria in
      Henan Province from 2012 to 2014, so as to provide the evidence for proposing the
      reasonable suggestions for imported malaria prevention and control. METHODS: The
      data of imported malaria were collected and the epidemic characteristics were
      analyzed in Henan Province from 2012 to 2014. RESULTS: A total of 569 imported
      malaria cases were reported in Henan Province from 2012 to 2014, including 445
      cases of falciparum malaria, 48 cases of vivax malaria, 61 cases of ovale
      malaria, 14 cases of quartan malaria, and 1 case of mixed infection. All the
      malaria cases were confirmed in laboratory. During the three years, the time of
      higher incidence was in Spring Festival, and May and June, and the cases mainly
      distributed in Luoyang, Zhengzhou, Puyang, Xinxiang, Anyang, Xuchang and Nanyang
      cities, accounting for 68.54%. Totally 82.43% of the patients were male youth and
      middle-aged. Of the 569 patients, 534 (93.85%) returned from Africa and 35
      (6.15%) returned from Southeast Asian countries. The average time was 6.22 d and
      the median was 4 d from the onset to diagnosis. Among 569 cases, 290 (50.97%)
      were confirmed by different levels of centers for disease prevention and control,
      and 279 (49.03%) were diagnosed by different levels of medical institutions.
      CONCLUSIONS: The imported malaria cases have been increased obviously in recent 3
      years in Henan Province. Therefore, the health education for the knowledge about
      malaria prevention and control, and the technician training should be
      strengthened.

PMID- 29376292
TI  - [Analysis of malaria epidemic situation in Pingguo County, Guangxi Zhuang
      Autonomous Region from 1951 to 2014].
AB  - OBJECTIVE: To explore the law and distribution characteristics of malaria
      prevalence in Pingguo County, Guangxi Zhuang Autonomous Region, so as to provide
      the evidence for formulating the targeted control strategy and measures after
      malaria elimination. METHODS: The data of malaria epidemic situation in Pingguo
      County from 1951 to 2014 were collected and analyzed with the retrospective
      epidemiological method. RESULTS: From 1951 to 2014, there were 71 365 malaria
      cases reported in the county. The malaria incidence dropped from 429.43/10 000 in
      1960 to 0 in 1993. Since 2002, there was no local endogenous infection case
      reported. In 1993, this county achieved the standard of malaria elimination
      basically, and in 2014, passed the examination and evaluation of malaria
      elimination. CONCLUSIONS: In Pingguo County, the comprehensive malarial control
      strategy is effective in different stages. In the future, the monitoring of
      mobile population and dealing with imported malaria cases timely is the key of
      consolidation of malaria control achievements.

PMID- 29376293
TI  - [Epidemiological situation of human parasitic diseases through three
      investigations in Jinhu County, Jiangsu Province].
AB  - OBJECTIVE: To understand the epidemiological situation of human parasitic
      diseases in Jinhu County, so as to provide the evidence for formulating further
      control strategy. METHODS: The investigated local residents were sampled by the
      random cluster sampling method in 1989, 1999 and 2015. The infections of
      intestinal helminthes were detected by Kato-Katz technique, the eggs of
      Enterubius vermicularis were examined by cellophane anal swab for children, the
      intestinal protozoa were examined by the saline smear and iodine staining
      methods. RESULTS: The total rates of parasitic infections were 62.57%, 9.32% and
      0.49% in 1989, 1999 and 2015, respectively. Compared to those in 1989 and in
      1999, the infection rate in 2015 was decreased by 99.22% and 94.74%,
      respectively. The numbers of detected parasite species were 14, 10 and 4 in 1989,
      1999 and 2015, respectively. The intensities of infections were mainly mild in
      three investigations, and the intensities of all the infections in 2015 were
      mild. The species of infected parasites were mainly single, however, multiple
      infections were observed in 1989, including 4 parasite species (0.72%) and 3
      parasite species (7.02%). Only in 1989, the difference between sexes was
      significant and the infection rate of the female was higher than that of the male
      (chi2 =18.01, P<0.01). CONCLUSIONS: The infection rates of human parasites are
      decreased gradually and stabilized at the low level in Jinhu County. However, the
      surveillance work still should be strengthened to consolidate the achievement.

PMID- 29376294
TI  - [Study on Histiostomas apromyzarum breeding in traditional Chinese medicine
      Rhizoma bletillae].
AB  - OBJECTIVE: To investigate the Histiostomas apromyzarum breeding in traditional
      Chinese medicine Rhizoma Bletillae. METHODS: The scurf and dust of R. bletillae
      were obtained by brushing, and the mites samples were separated and identified.
      RESULTS: Totally 520 g samples were collected, and 56 adult mites (female-male
      ratio 0.12) and 18 dormant bodies were obtained from the samples, and they were
      identified as H. apromyzarum with an average breeding density of 0.14/g.
      CONCLUSIONS: H. apromyzarum could breed on the traditional Chinese medicine R.
      bletillae, and the corresponding control measures should be strengthened.

PMID- 29376295
TI  - [Status and challenges for schistosomiasis in transmission-interrupted areas in
      Jiangxi Province].
AB  - This report analyzes the status of schistosomiasis epidemic, surveillance and
      challenges in transmission-interrupted areas of Jiangxi Province. There are 24
      schistosomiasis transmission interrupted counties (cities, districts) among 39
      endemic counties (cities, districts). Among the 24 counties, there are 6 counties
      with Oncomelania hupensis snails and 461 villages endemic, with 1.29 million
      residents. Since 2009, there have not been acute and chronic cases of
      schistosomiasis and all the patients are historical advanced schistosomiasis
      cases. The area with snail habitats is 37.02 hm2. Since 2015, the schistosomiasis
      surveillance has covered the entire transmission interrupted areas. However,
      there are still many challenges, such as endemic instability, weak surveillance
      capacity, lack of surveillance awareness and other issues. Towards the
      schistosomiasis elimination, the surveillance should be based on the snail
      monitoring mainly, supplemented by the mobile population monitoring, and in
      addition, the capacity building, standardized report of endemic, and snail
      habitat reform should also be further strengthened.

PMID- 29376296
TI  - [Analysis of demands of African students for China-Africa malaria prevention
      training].
AB  - OBJECTIVE: To understand the demands of African students on the China-Africa
      malaria prevention training programs as well as explore further suggestions on
      the student selection and course content design. METHODS: A self-administered
      questionnaire survey was conducted, and all the students who attended in the
      malaria prevention training courses in 2014 and 2015 were included. The Chi
      square test was conducted to analyse the correlations between professional
      backgrounds, work statues and training needs. RESULTS: A total of 161 individuals
      were sampled eventually. These participants were trained in either English
      (58.4%) or French (41.6%). Most of the participants were male (69.3%), the major
      of them were mainly clinical technology specialty (40.0%), and most of them
      worked in malaria area within 10 years (56.4%). Moreover, 48.2% of the
      participants used more than 76% of total work time on malaria control, and more
      than 80% worked in national or provincial/municipal level. The working areas of
      these participants were focused on clinical field (41.4%) and official field
      (29.9%), and only a few of them were from research positions (11.9%). The most
      needed course content in malaria training was strategy and epidemiology knowledge
      for malaria prevention and control (65.5%), while clinical workers were most
      needed to be trained (39.2%). The participants who came from French speaking
      countries preferred strategy training (chi2 = 12.528, P < 0.01), and those worked
      in the national level were aslo more likely to choose strategies training course
      (chi2 = 10.508, P < 0.05). CONCLUSIONS: Currently, the China-Africa malaria
      prevention training programs could basically satisfy African students'needs.
      However, more aimed courses should be designed according to their professional
      backgrounds, national situation, work experiences on malaria control, and
      institutional levels.

PMID- 29376297
TI  - [Epidemiological analysis of imported malaria in Hailing District, Taizhou City
      from 2010 to 2015].
AB  - OBJECTIVE: To investigate the epidemiological characteristics of imported malaria
      in Hailing District, Taizhou City, so as to provide the evidence for formulating
      the effective prevention and control strategy. METHODS: The network reports,
      questionnaires and epidemic reports of imported malaria cases in Hailing District
      from 2010 to 2015 were collected and analyzed retrospectively. RESULTS: From 2010
      to 2015, totally 46 cases of imported malaria were reported, including 40 cases
      of falciparum malaria (86.96%), 4 cases of ovale malaria (8.70%), 1 case of
      quartan malaria (2.17%) and 1 case of multi-infection of falciparum malaria and
      tertian malaria (2.17%). No seasonal trend of time of the disease onset was
      observed. All the patients were return abroad with clear residence histories in
      malaria epidemic areas. The average time from disease onset to definite diagnosis
      was 2 d and 8 patients were definitely diagnosed within 24 h. All the 46 patients
      were cured. CONCLUSIONS: All the malaria cases reported were imported cases in
      Hailing District in the last five years. Effective prevention and control
      measures are the key to the malaria elimination.

PMID- 29376298
TI  - [Quality analysis of malaria blood smears of fever patients in Changzhou City in
      2014].
AB  - OBJECTIVE: To understand the quality of blood smears for Plasmodium detection in
      Changzhou City, so as to provide the technical support for malaria surveillance
      in the post-elimination period. METHODS: The blood smears of fever patients from
      each cities (districts) in Changzhou City in 2014, including more than 3% of the
      negatives and all the positives, were selected. The quality of the blood smear
      making, dyeing, cleanliness and results were reviewed by the experts from the
      municipal malaria microscopy station, and the data were analyzed statistically.
      RESULTS: Totally 996 negative blood smears were reviewed in 2014, with a review
      rate of 4.52%. The qualified rates of blood smear making, dyeing and cleanliness
      were 92.87%, 93.27% and 94.48%, respectively. A total of 34 positive blood smears
      were reviewed, and there were no false detections and leak detections. The
      qualified rates of blood smear making and dyeing were more than 90% in all the
      seven cities (districts). As for qualified rate of cleanliness, except the rate
      in Qishuyan District (81.36%), those in the other six cities (districts) were all
      above 90%. The qualified rates of blood smear making, dyeing and cleanliness were
      all more than 90% in first-class, second-class and third-class hospitals. The
      major quality defects of the blood smears were sediment, abnormal making and
      thick membrane shedding, and the proportions were 25.91%, 21.76% and 19.17%,
      respectively. CONCLUSIONS: The quality of blood smears for Plasmodium detection
      in Changzhou City is satisfying. In the future, the training and supervision
      still should be strengthened to guarantee the capacity of microscopic
      examinations for Plasmodium detection in the surveillance of post-elimination
      period.

PMID- 29376299
TI  - [Clinical characteristics of 96 patients with advanced schistosomiasis in
      Yingcheng City].
AB  - OBJECTIVE: To understand the clinical characteristics of patients with advanced
      schistosomiasis in Yingcheng City, so as to provide evidences for the assistance
      work of advanced schistosomiasis. METHODS: The clinical data of all the advanced
      schistosomiasis patients in Yingcheng City were collected and analyzed. RESULTS:
      Up to December 30, 2014, there were 96 advanced schistosomiasis patients in
      Yingcheng City, among which, 68 cases (70.8%) were male, 28 cases (29.2%) were
      female, and their average age was 64.2 years. Most of the patients (90.6%) were
      ascitic type, followed by splenomegaly type (5.2%), colon proliferation type
      (2.1%), and dwarf type (2.1%). Totally 48 cases (50.0%) were positive in
      immunological detections, among which 8 cases (8.3%) were positive in ELISA and
      12 cases (12.5%) were positive in IHA. For all the 4 indexes of hepatic fibrosis
      (HA, LN, CIV and PCIII), only 15 cases (15.6%) were normal. CONCLUSIONS: Though
      Yingcheng City has reached the criteria of transmission control, the hepatic
      fibrosis of some patients continues to progress. Therefore, the intensity of the
      treatment and assistance could not be weakened, especially for those of the
      ascitic type patients.

PMID- 29376300
TI  - [Diagnosis and treatment of imported African schistosomiasis].
AB  - This paper summarizes the clinical diagnosis and treatment of imported African
      schistosomiasis, in order to make the therapeutic standards. Imported African
      schistosomiasis includes mainly schistosomiasis haematobia and schistosomiasis
      mansoni in China. In order to set up the operational standards, enhance
      diagnostic and cure rates, and reduce the complications, we review the related
      literature combined with our experience over years, and summarize, in this paper,
      the pathogenic mechanism, and key points of clinical diagnosis and treatment of
      schistosomiasis haematobia and schistosomiasis mansoni, so as to provide the
      reference for clinical doctors.

PMID- 29376301
TI  - [Laboratory analysis of the first case of imported oval malaria in Rizhao City].
AB  - OBJECTIVE: To diagnose the first imported case of Plasmodium ovale infection by
      laboratory detection. METHODS: The epidemiological data and blood samples of the
      case were collected, and the samples were detected by the microscopic
      examination, rapid diagnostic test (RDT) and nested PCR. RESULTS: The patient was
      a construction worker backing from Congo, Africa. He experienced the symptoms of
      irregular fever and weakness one month after returning in Lingyang Town, Junxian
      County. The results of RDT only suggested no-Plasmodium falciparum infection.
      Under the microscope, it was seen that the infected RBC were obviously disfigured
      and in irregular shape, the ring forms were thick and big, and also thick
      granulas in big trophozoite stage and schizont stage were found. The results of
      PCR showed that the size of amplified product was about 800 bp, which was
      conformed to that of P. ovale. CONCLUSIONS: Though microscopic examination is the
      golden standard for malaria diagnosis, as P. ovale is difficult to be identified
      under microscope, the microscopic method combined with PCR test can be used for
      definite diagnosis.

PMID- 29376302
TI  - [One hepatic echinococcosis patient complicated with systemic sclerosis].
AB  - This article reports one hepatic echinococcosis patient complicated with systemic
      sclerosis. His clinical manifestations were the progressive fibrosis of the skin,
      sour regurgitation, and belching. The blood examination showed that eosinophils
      was reduced, and antinuclear antibody (ANA) was positive at 1:100 in cytoplasm
      particle type. He was given prednisone acetate 25 mg, q. d., aspirin 100 mg, q.
      d., centella triterpenes cream 12 mg t. i. d., esomeprazole 40 mg q. d., and
      domperidone 10 mg t. i. d. After one week, the Rodnan skin score reduced from 27
      to 17. The liver hydatid cyst resection was performed, and the follow-up showed
      that his clinical manifestations improved and the Rodnan skin score reduced
      further.

PMID- 29376303
TI  - [Current trends in nutrigenomics of obesity].
AB  - One of the most general chronic illness in the world is obesity, which lead to
      progression of cardiovascular diseases, diabetes mellitus type 2, metabolic
      syndrome and other diseases. Slow body weight gain, that leads to overweight, is
      a long-term aftereffect of a long-term positive energy balance, which occurs as a
      result of physical activity reduction and calorie intake increasing. Trend in the
      reduction of physical activity and increasing the caloric value of food intake is
      probably the main reason of increasing patients with obesity, but it's necessary
      to mention that this tendency occurs because of genetic variation in population.
      The volume of scientific information, relevant to the problem of genetic
      predisposition testing to obesity, is highly increasing. This article provides an
      overview of recent data on the genetics of obesity and the role of genetic
      testing of candidate genes polymorphisms, as well as genes associated with
      carbohydrate and lipid metabolism disorders (FTO, ADRB2, ADRB3, PPARG and a
      number of others). The role of nutrigenomics in personalization of diet treatment
      for obesity.

PMID- 29376304
TI  - [Comparative characteristics of in vivo models of hyperlipidemia in Wistar rats
      and C57Bl/6 mice].
AB  - In vivo simulation of lipid disorders (hyperlipidemia, obesity, metabolic
      syndrome, atherosclerosis) is of considerable interest to search for genomic,
      transcriptomic and metabolomic markers that allow for differential diagnosis,
      prognosis and selection of personalized diet therapy in patients with such
      pathology. The aim of the study was the development and characterization of basic
      biochemical parameters of in vivo models of alimentary hyperlipidemia in outbred
      rats and inbred mice. The experiment was con-ducted on 48 growing female Wistar
      rats, and 48 growing female mice of line C57Black/6, which were divided into 12
      groups of 8 animals per group. Within 63 days the rats and mice of first
      (control) group received a balanced semi synthetic diet (BD), the animals of the
      second groups - high-fat diet (HFD) with 30% of the total fat by weight of dry
      feed, third groups - BD and fructose solution (Fr) instead of water, the fourth
      groups -HFD + Fr, fifth groups - BD supplemented with 0.5% cholesterol (Cho) by
      weight of dry feed, sixth groups - BD with Cho and Fr. The amount and composition
      of diets consumed were corrected during the experiment for their closest approach
      in calories. After removal of animals from the experiment there were determined
      the mass of internal organs, HDL, LDL, total cholesterol, triglycerides, glucose
      in blood plasma, total lipids and their fatty acid composition in liver, ghrelin,
      GIP, GLP-1, glucagon, leptin, PAI-1, resistin levels in blood plasma. It was
      found that in both species the liver is the most sensitive to nutritional
      imbalance, nutrient exerting the greatest impact on this was Fr. In rats, as
      compared to mice, there was significantly more pronounced shifts in lipoprotein
      spectrum in response to nutritional imbalances, especially to the consumption of
      additional Cho, which was manifested in an increase of LDL, decrease of HDL and
      magnification of atherogenic index. In the liver of rats fed diets with Cho,
      marked steatosis developed manifested in a disproportionate increase in the lipid
      content and accompanied by changes in their fatty acid composition, especially in
      the ratio omega6 to omega3 PUFAs. Changing of hormones - regula-tors of
      carbohydrate metabolism (GLP, glucagon) and ghrelin was significantly greater in
      mice than in rats as a result of consumption of additional Fr. Effect had the
      opposite direction in two species of Cho and Fr combining on leptin levels. The
      significance is dis-cussed of the revealed interspecies differences in the light
      of the characteristics of lipid and glucose metabolism in these two lines of
      animals that are the most common models of alimentary-dependent diseases.

PMID- 29376305
TI  - [State of homeostasis under administration of bear fat in rats with exogenous and
      endogenous thrombinemia].
AB  - In experimental studies on 448 rats treated with bear fat diet (0.08 ml/100 g
      body weight), the nature and mechanisms of influence of this additive on the
      process of blood coagulation in experimental thromboplastinemia of different
      origin has been studied. As a result of intravenous injection in the jugular vein
      of a suspension of thrombin (exog-enous thrombinemia) all clothingsee tests
      lengthened in the control animals (p<0.05): prothrombin time by 11.1%, activated
      partial thromboplastin time - by 13.4%, thrombin time by 16.8%. Fibrinogen fell
      by 1.9 fold, that was accompanied by increase of the level of soluble fibrin
      monomer complexes and reduce of activity of antithrombin III by 20.2%. At the
      same time severe thrombocytopenia developed with a relative increase in the num
      ber of activated forms (by 73.1%). Consumption coagulopathy was also observed in
      rats treated with bear fat, but the potential of hemostatic cascade and
      anticoagulation system remained high (judging by the tests PTV, thrombin time and
      content of antithrombin III). Under endogenous thromboplastinemia caused by
      combined stress (hypothermia + physi-cal activity) in animals of the control
      group on the background of the shortening of the APTT (by 24.9%) and PTV (16.8%),
      RCMP concentration increased by 52% and activity of antithrombin III increased
      compensatory. There was an increase of platelet count, due to the activated
      forms. To 3 h signs of hypocoagulation aggravated even more. In animals treated
      with bear fat, the results of clothing tests did not differ from the original
      figures, and by 3 h, the majority of the indicators have reached their original
      values. The increase in platelet count has not been observed.

PMID- 29376306
TI  - [Influence of linseed oil and deiterium depleted water on isotopic D/H
      composition and functional antioxidant defense of the hepatobiliary system in
      rabbits with carbon tetrachloride intoxication].
AB  - The article presents results of studying the influence of linseed oil and
      drinking diet with a modified isotopic composition with low deuterium content on
      indicators of prooxidant-antioxidant system during modeling of liver toxicity.
      The research was performed on 36 rabbits (weighing 3.1-3.5 kg) which were divided
      into 4 groups. Group 1 consisted of control animals; in group 2, 3 and 4 in
      rabbits the liver toxicity was modeled by administration of CCl4
      (intraperitoneally, in the form of a 50% oil solution, 1 ml per kg bw, 2 times a
      week for 30 days); nutritional correction using flaxseed oil (0.1 ml per 100 g
      bw) and drinking diet with deuterium depleted water (50 ppm) was carried out in
      animals from groups 3 and 4 respectively, for 30 days prior to simulation of
      toxic hepatitis and more throughout the experiment. Using the method of nuclear
      magnetic resonance and mass spectrometry the influence of deuterium depleted
      water on D/H composition of the blood plasma, bile and liver tissues was
      determined: the deuterium concentration in these biological materials significant
      decreased. The most significant decrease in the deuterium content (30.2% compared
      with the control group) was found in bloodplasma in animals from group 4. The
      study of the state of prooxidant-antioxidant balance of the liver and bile showed
      oxidative stress at the local level, with the toxic effects of carbon
      tetrachloride. This was followed by EPR spectroscopy data pronounced increase of
      the number of paramagnetic centers in the hepatocytes by 5.4, 1.9 and 2.8 fold in
      animals of 2, 3 and 4 groups, respectively (compared to the indicators of the
      first group). There was also increase in the intensity of free radical oxidation
      processes in the bile with a simultaneous reduction of its antioxidant activity,
      which was significantly less distinct (on average 51.18-59.8%, p<0.05) in animals
      treated with nutritional correction, indicating that higher functional activity
      of protective systems involved in recycling prooxidant factors using dietary
      lipophilic antioxidants and water with low deuterium content. Overall, the
      results of the present study indicate that existing in the liver and bile
      autonomous mechanisms of regulation of the state of prooxidant-antioxidant
      systems are quite sensitive to the effects of antioxidant factors of lipophilic
      nature and shifts of isotopic D/H gradient, and suggest usefulness of the
      products that can affect these indicators to increase adaptive capabilities of
      the organism during intoxication.

PMID- 29376307
TI  - [Evaluation of antioxidant properties of enriched bakery products in experiment
      on laboratory animals].
AB  - The purpose was to study the effect of enriched bakery products in the diet of
      rats on indicators of prooxidant-antioxidant system of blood serum. Experiment
      was carried out on male Wistar rats with initial weight 140-180 g. After a
      quarantine during the preparatory period rats for 14 days were accustomed to the
      partial (50%) replacement of the standard diet by bakery products with standard
      compound-ing. Then, 7 groups of rats were formed: the 1st group of rats (control
      group, n=10) continued to receive bakery products of a standard composition;
      groups with the 2nd on 7th (experimental, n=8 in everyone) received enriched
      bakery products: the 2nd group - with blueberry powder; the 3rd group - with
      mountain ash powder; the 4th group - with sea-buckthorn powder; the 5th group -
      with flour of a pine nut; the 6th group - with rice bran oil; the 7th group -
      with pumpkin oil. The intensity of free radical oxidation and antioxidant
      activity (by chemiluminescence method), activity of superoxide dismutase and
      level of secondary oxidation products reacted with thiobarbituric acid (by
      spectrophotometry) were monitored in rat blood serum. It has been shown that the
      use of bakery products with different compounding in the animal diet had
      different effects on indicators of prooxidant-antioxidant system of blood serum.
      Bakery products containing sea buckthorn pomace powder, flour of pine nut and
      rice bran oil reduced intensity of free radical oxidation in rat blood serum by
      36.0, 24.6 and 18.8%, respectively. It is suggested that bakery products
      containing flour of pine nut products brake a free radical oxidation in rat blood
      serum in case of simultaneous content of natural antioxidants and melanoidins.
      The anthocyanins of powder from blueberry berries can render antioxidant effect
      and slow down formation of by-products of oxidation. No statistically significant
      change on indicators of prooxidant-antioxidant system of blood serum of rats
      treated with bakery products with rowan powder or pumpkin oil was found, that may
      be due to animal refusal to eat such products.

PMID- 29376308
TI  - [The study of physiological effect of fruit and vegetable powders in animal
      experiment].
AB  - The results of the study of the mineral and vitamin composition of fruit and
      vegetable powders, as well as their influence on the clinical and physiological
      parameters in laboratory animals (body weight, behavior patterns, functional
      state of the cardiovascular and nervous systems, general clinical and biochemical
      parameters of blood) were obtained. The study was performed on white Wistar rats
      initial body weight 190+/-20 g that were previously kept in quarantine for 5
      days. One control group and six experimental groups (6 animals in each) were
      formed. Within 28 days animals from experimental groups were administered the
      diet supplemented with fruit or vegetable powder (carrot, squash, beet, apples,
      cabbage, pumpkin) in an amount of 3% by weight of the feed. When carrot powder
      was consumed, amplification processes of catabolism of proteins, fats and
      carbohydrates, as evidenced by an increase in blood levels of bilirubin, activity
      of alkaline phosphatase, GGT, LDH and significant reduction of cholesterol and
      triglyceride level occurred. In animals that received zucchini powder, body
      weight increased by 15.6% compared to the initial, as well as the activation of
      the immune response, enhance of carbohydrate metabolism (urea level and AST
      activity decreased under normal blood level of total protein, albumin fraction,
      bilirubin, creatinine, and LDH and ALT activity) and fat metabolism (cholesterol
      and triglyceride level reducing) was observed. Consumption of beet powder caused
      an increase in the number of red blood cells and platelets, elevated protein and
      fat metabolism (decrease in albumin, bilirubin, creatinine and urea level at
      normal parameters of total protein, glucose, AST activity, marked decrease in the
      level of triglycerides and cholesterol), had a stimulating effect on the heart
      (blood pressure and pulse rate increased). Consumption of apple powder caused the
      activation of the immune response, improved blood formation, activated energy
      metabolism (decrease in creatinine, urea, albumin, bilirubin, cholesterol and
      triglycerides level, AST, ALT and alkaline phosphatase activity), slowed heart
      rate and had a hypotensive effect. After uptake of cabbage powder, weight gain by
      21.7% from the initial weight, increase in alkaline phosphatase and GTT activity,
      activation of protein metabolism (decrease in the number of total protein,
      albumin, bilirubin level) has been revealed. In the study of orienting-motor
      functions it was found that physical activity and "mink" reflex increased in this
      animals as well as swimming time before exhaustion raised by 27.1% compared to
      control animals. Body weight increased mostly pronounced (by 29.0% of the
      original) when pumpkin powder was consumed. Addition of pumkin powder contributed
      to the activation of blood immune system; protein metabolism increase (raise of
      total protein and urea, reduction in bilirubin level, AST activity); the duration
      of swimming to exhaustion increased by 37.9%, compared with the control group. No
      any negative deviation was found in the state of animals under administration of
      investigated plant powders.

PMID- 29376309
TI  - [Investigation of the effect of oil and flour from wheat germ meal on lipid
      metabolism of students and teachers of the university].
AB  - The results of investigation of alimentary correction of lipid metabolism under
      the admin-istration of processed products from wheat germ - oil (with the content
      of policosanol at least 1.5-8.0 mg/100 g, vitamin E - 180-200 mg/100 g, PUFA - 60
      65%) and cake flour (with the content of protein - 30-35%, oil with analogue
      composition -5-7%, digestible carbohydrates - 45-47%, fiber - 18-26%, vitamins
      B1, B3, B6, B9, E, PP, minerals and trace elements - Zn, Mn, K, Fe, Se, P) are
      presented. Volunteers among teachers and students of the university aged 16 to 65
      years daily consumed wheat germ oil obtained by cold pressing in an amount of 3.5
      g, regardless of the meal within 30 days. Then a part of them (30 persons)
      consumed daily 50 g of oil cake obtained after pressing oil, which provided the
      intake of the same amount of oil (3.5 g). Lipid metabolism param-eters were
      monitored in experiment participants before receiving the processed products of
      wheat germ, after germ meal intake and beyond 30 and 60 days after consumption of
      wheat germ. Data analysis was carried out on three age groups: 16-24, 25-44 and
      45- 65 years. All participants of the experiment showed a reduction in total
      cholesterol level by 6-8%, increasing the concentration of HDL cholesterol by 3
      24%, lowering LDL cholesterol concentrations by 4-21%, reduction of triglyceride
      concentration by 12-24%, a positive correction of atherogenic factor values by
      for 10-25%. Prolonged action of the investigated foods was established: lipid
      metabolism parameters in the tested group were better than in the control group
      after 30 days of intake discontinuation of oil or wheat germ flour, the positive
      adjustment effect disappeared 60 days after consuming the products. The findings
      demonstrate a positive effect on the normalization of lipid metabolism when cake
      flour of wheat germ was administered in daily food ration, similar to the effect
      of oil intake, which is important for the prevention of cardiovascular diseases
      and atherosclerosis. Given the significant production of cake flour of wheat germ
      (up to 90-95% of the raw material) and its not high cost as a secondary
      biological resource, this product can be recommended to the introduction in the
      diet of organized groups, including socially vulnerable groups.

PMID- 29376310
TI  - Modification of vitamin-mineral diet composition as a model of adaptive potential
      reducing in laboratory animals.
AB  - This publication presents the results of research that was aimed at elaboration
      of adaptive potential reducing model, intended for toxicological experiments. Two
      series of research (with a duration of 70 days each) were conducted on Wistar
      rats. In the 1st series five groups of animals received diets with 100, 75,50,25
      and 0% of vitamins B1, B2, B3, B6 and minerals(Fe3+ and Mg2+); in the 2nd series
      four groups of animals received diets with 21.37, 9.94, 4.62, 2.15% of this
      vitamins and minerals. In the 1st series of studies the intervals of maximum,
      medium and minimum content of essential nutrients in the diet was established; in
      the 2nd series the range of the lowest possible concentrations of these elements
      that provided the lowest level of adaptive potential and not causing the
      pathology development was determined. The certain set of hematological,
      biochemical, immunological and other indicators were investigated, this article
      analyzes the results of zoometric studies, mortality of animals, as well as the
      results of antioxidant status (activity of superoxide dismutase, catalase,
      glutathione peroxidase, glutathione reductase and malondialdehyde content in red
      blood cells) studies. Based on the evaluation of the data which were obtained in
      the 1st series, it follows that a dose reduction of relevant essential nutrients
      to 25% didn't significantly affect the values of the studied indicators, and the
      complete elimination of these substances resulted in massive death of animals. In
      the 2nd series a significant differences between the groups were observed from
      the range of increased mortality (groups with 2.15 and 4.62% content of essential
      nutrients) to the range of deviations from central tendency of some parameters
      (group with 21.37% content). The data allowed to trace the dependence of these
      differences on the levels of vitamins and minerals in the diet. The results were
      used to determine threshold values of vitamins and minerals that provided the
      necessary reduction of the adaptive potential level in male and female rats.
      Taking into account the risk of pathology development, three dosages of essential
      substances have been established - optimal, marginal and submarginal, which
      provide consistent decline of adaptive potential of laboratory animals: 75, 30
      and 19% for males and 75, 28 and 18% for females, respectively. The modification
      of vitamin and mineral composition of the diet can be used as a model of adaptive
      potential reduce in toxicological research.

PMID- 29376311
TI  - Influence of nanosized amorphous silica on assimilation of vitamins B1, B2 and B6
      in rats.
AB  - Amorphous silica (SiO2) in the form of nanoparticles (NPs) is widely used as a
      food additive E551 in many enriched foods and food supplements. The aim of this
      study was to evaluate the effect of oral administration of SiO2 NPs on
      assimilation and metabolism of vitamins B1, B2 and B6 in laboratory rats.
      Amorphous SiO2 "Orisil-300 (r)" was used with the size of the primary NPs 20-60
      nm according to the electronic, atomic force microscopy and dynamic light
      scattering. The experiment was conducted on 8 groups of growing male Wistar rats
      (with initial body weight 70-80g) number, respectively, 7, 7, 10, 10, 12, 12, 14
      and 16 animals. Animals of the 1st, 3rd, 4th and 5th groups received through-out
      the experiment balanced semi-synthetic diet. Animals of the 2nd group received a
      diet depleted of vitamins B1, B2 and B6 until day 21; animals of the 6th, 7th and
      8th groups -the same diet from the 1st to the 21th day, and then, before the
      closure of the experiment, the diet provided with the indicated B vitamins at
      100% of normal level. From day 22 of experiment and until the end at day 29 the
      animals of the 3rd and 6th groups received deionized water (placebo) through
      intragastric gavage; rat of the 4th and 7th groups -aqueous suspension of SiO2
      dose of 1 mg/kg body weight /day, and the 5th and 8th group -100 mg/kg/day.
      Urinary excretion of thiamine, riboflavin, 4-pyridoxilic acid and liver and brain
      content of vitamins B1 and B2 (after acid and enzyme hydrolysis) were deter-mined
      by fluorimetric methods. It was found that rats in group 2 lagged in weight gain
      at day 21 significantly compared to group 1, and developed a marked deficiency of
      vitamins B1, B2 and B6 according to studied safety parameters. In groups from 6
      to 8 at day 29 par-tial recovery was achieved in vitamin status. Administration
      of SiO2 to animal of groups 4 and 5, with normal consumption of B vitamins, had
      no significant effect on any param-eters of vitamin status in comparison to group
      3. However, intragastric administration of SiO2 led in animals of groups 7 and 8
      to an increase in the urinary excretion of vitamins B1 and B2 and lowering of
      their content in liver as compared to group 6. Administration of SiO2 had no
      effect on indices of vitamin B6 sufficiency. Possible reasons are discussed for
      the adverse lowering impact of SiO2 NPs on the availability of vitamins B1 and B2
      and their increased clearance from the body.

PMID- 29376312
TI  - Optical Anapole Metamaterial.
AB  - The toroidal dipole is a localized electromagnetic excitation independent from
      the familiar magnetic and electric dipoles. It corresponds to currents flowing
      along minor loops of a torus. Interference of radiating induced toroidal and
      electric dipoles leads to anapole, a nonradiating charge-current configuration.
      Interactions of induced toroidal dipoles with electromagnetic waves have recently
      been observed in artificial media at microwave, terahertz, and optical
      frequencies. Here, we demonstrate a quasi-planar plasmonic metamaterial, a
      combination of dumbbell aperture and vertical split-ring resonator, that exhibits
      transverse toroidal moment and resonant anapole behavior in the optical part of
      the spectrum upon excitation with a normally incident electromagnetic wave. Our
      results prove experimentally that toroidal modes and anapole modes can provide
      distinct and physically significant contributions to the absorption and
      dispersion of slabs of matter in the optical part of the spectrum in conventional
      transmission and reflection experiments.

PMID- 29376313
TI  - Laser Tuning in van der Waals Crystals.
AB  - The great progress that optoelectronic technologies have achieved in van der
      Waals crystals promises the development of next-generation two-dimensional (2D)
      integrated optoelectronic systems (IOSs). Here, relying on the anomalous
      avoidance of pump-light absorption, the harvest of extremely strong Raman
      scattering, and the achievement of polarization inheritance by the designed
      optical geometry, we realized laser wavelength tuning with ultrahigh precision
      (0.01 nm/25 K) in layered MoS2 and WS2 by adjusting the temperature. Our results
      offer a potential approach for 2D laser tuning, while also building a substantial
      theoretical foundation, which might be of use in developing future wavelength
      division-multiplexing technology in 2D IOSs.

PMID- 29376314
TI  - High Anisotropy in Tubular Layered Exfoliated KP15.
AB  - Two-dimensional (2D) materials with high anisotropic properties, such as black
      phosphorus and ReS2, show amazing potential for applications in future
      nanoelectronic and optoelectronic devices. However, degradation of black
      phosphorus under ambient conditions and the expensiveness of Re block their
      application. In this study, another layered material, KP15, that has highly
      anisotropic properties was successfully prepared. The detailed crystal structure
      and electron-density distribution calculation reveal that KP15 exhibits an
      anisotropic layered structure with two rows of P tubes connected by K atoms that
      are antiparallel in a single layer. Outstanding chemical stability, angular
      dependence of the Raman response, excitation, and exciton emission at room
      temperature have been found in exfoliated KP15 nanoribbons. Importantly, the
      exciton emission at room temperature suggests the existence of a large exciton
      binding energy. Our results indicate that, because this layered material, KP15,
      has high anisotropic properties and ultrachemical stability and is derived from
      abundant raw materials, it has great potential for applications in optoelectronic
      devices.

PMID- 29376315
TI  - Sensitive Monitoring of Enterobacterial Contamination of Food Using Self
      Propelled Janus Microsensors.
AB  - Food poisoning caused by bacteria is a major cause of disease and death
      worldwide. Herein we describe the use of Janus micromotors as mobile sensors for
      the detection of toxins released by enterobacteria as indicators of food
      contamination. The micromotors are prepared by a Pickering emulsion approach and
      rely on the simultaneous encapsulation of platinum nanoparticles for enhanced
      bubble-propulsion and receptor-functionalized quantum dots (QDs) for selective
      binding with the 3-deoxy-d-manno-oct-2-ulosonic acid target in the endotoxin
      molecule. Lipopolysaccharides (LPS) from Salmonella enterica were used as target
      endotoxins, which upon interaction with the QDs induce a rapid quenching of the
      native fluorescence of the micromotors in a concentration-dependent manner. The
      micromotor assay can readily detect concentrations as low as 0.07 ng mL-1 of
      endotoxin, which is far below the level considered toxic to humans (275 MUg mL
      1). Micromotors have been successfully applied for the detection of Salmonella
      toxin in food samples in 15 min compared with several hours required by the
      existing Gold Standard method. Such ultrafast and reliable approach holds
      considerable promise for food contamination screening while awaiting the results
      of bacterial cultures in a myriad of food safety and security defense
      applications.

PMID- 29376316
TI  - Understanding Excess Emissions from Industrial Facilities: Evidence from Texas.
AB  - We analyze excess emissions from industrial facilities in Texas using data from
      the Texas Commission on Environmental Quality. Emissions are characterized as
      excess if they are beyond a facility's permitted levels and if they occur during
      startups, shutdowns, or malfunctions. We provide summary data on both the
      pollutants most often emitted as excess emissions and the industrial sectors and
      facilities responsible for those emissions. Excess emissions often represent a
      substantial share of a facility's routine (or permitted) emissions. We find that
      while excess emissions events are frequent, the majority of excess emissions are
      emitted by the largest events. That is, the sum of emissions in the 96-100th
      percentile is often several orders of magnitude larger than the remaining excess
      emissions (i.e., the sum of emissions below the 95th percentile). Thus, the
      majority of events emit a small amount of pollution relative to the total amount
      emitted. In addition, a small group of high emitting facilities in the most
      polluting industrial sectors are responsible for the vast majority of excess
      emissions. Using an integrated assessment model, we estimate that the health
      damages in Texas from excess emissions are approximately $150 million annually.

PMID- 29376317
TI  - Imaging Artifacts in Continuous Scanning 2D LA-ICPMS Imaging Due to
      Nonsynchronization Issues.
AB  - Pulsed laser ablation (LA) devices in laser ablation inductively coupled plasma
      mass spectrometry (LA-ICPMS) imaging have become very advanced, delivering laser
      pulses with high temporal accuracy and stable energy density. However,
      unintentional imaging artifacts may be generated in 2D element maps when the LA
      repetition rate and the data acquisition parameters of ICPMS instruments with a
      sequential mass spectrometer (i.e., quadrupole filter or sector-field mass
      spectrometer) are desynchronized. This may potentially lead to interference
      patterns, visible as ripples in elemental images, and thus, compromised image
      quality. This paper describes the background of aliasing in continuous scanning
      mode through simulation experiments and ways to modulate the effect. The
      existence of this image degradation source is demonstrated experimentally via
      real-life imaging of a homogeneous glass standard.

PMID- 29376318
TI  - Antibiotic Resistance ABC-F Proteins: Bringing Target Protection into the
      Limelight.
AB  - Members of the ATP-binding cassette (ABC)-F protein subfamily collectively
      mediate resistance to a broader range of clinically important antibiotic classes
      than any other group of resistance proteins and are widespread in pathogenic
      bacteria. Following over 25 years' of controversy regarding the mechanism by
      which these proteins work, it has recently been established that they provide
      antibiotic resistance through the previously recognized but underappreciated
      phenomenon of target protection; they bind to the ribosome to effect the release
      of ribosome-targeted antibiotics, thereby rescuing the translation apparatus from
      antibiotic-mediated inhibition. Here we review the ABC-F resistance proteins with
      an emphasis on their mechanism of action, first exploring the history of the
      debate about how these proteins work and outlining our current state of knowledge
      and then considering key questions to be addressed in understanding the molecular
      detail of their function.

PMID- 29376319
TI  - Multifunctional Nanoflowers for Simultaneous Multimodal Imaging and High
      Sensitivity Chemo-Photothermal Treatment.
AB  - Liver cancer is currently among the most challenging cancers to diagnose and
      treat. It is of prime importance to minimize the side effects on healthy tissues
      and reduce drug resistance for precise diagnoses and effective treatment of liver
      cancer. Herein, we report a facile but high-yield approach to fabricate a
      multifunctional nanomaterial through the loading of chitosan and metformin on Mn
      doped Fe3O4@MoS2 nanoflowers. Mn-doped Fe3O4 cores are used as simultaneous T1/T2
      magnetic resonance imaging (MRI) agents for sensitive and accurate cancer
      diagnosis, while MoS2 nanosheets are used as effective near-infrared photothermal
      conversion agents for potential photothermal therapy. The surface-functionalized
      chitosan was able not only to improve the dispersibility of Mn-doped Fe3O4@MoS2
      nanoflowers in biofluids and increase their biocompatibility, but also to
      significantly enhance the photothermal effect. Furthermore, metformin loading led
      to high suppression and eradication of hepatoma cells when photothermally
      sensitized, but exhibited negligible effects on normal liver cells. Due to its
      excellent combination of T1/T2 MRI properties with sensitive chemotherapeutic and
      photothermal effects, our study highlights the promise of developing
      multifunctional nanomaterials for accurate multimodal imaging-guided, and highly
      sensitive therapy of liver cancer.

PMID- 29376320
TI  - Unique Conformation in a Natural Interruption Sequence of Type XIX Collagen
      Revealed by Its High-Resolution Crystal Structure.
AB  - Naturally occurring interruptions in nonfibrillar collagen play key roles in
      molecular flexibility, collagen degradation, and ligand binding. The structural
      feature of the interruption sequences and the molecular basis for their functions
      have not been well studied. Here, we focused on a G5G type natural interruption
      sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this
      sequence possesses distinct properties compared with those of a pathological
      similar Gly mutation sequence in collagen mimic peptides. We determined the
      crystal structures of the host-guest peptide (GPO)3-GPOALO-(GPO)4 to 1.03 A
      resolution in two crystal forms. In these structures, the interruption zone
      brings localized disruptions to the triple helix and introduces a light 6-8
      degrees  bend with the same directional preference to the whole molecule, which
      may correspond structurally to the first physiological kink site in type XIX
      collagen. Furthermore, at the G5G interruption site, the presence of Ala and Leu
      residues, both with free N-H groups, allows the formation of more direct and
      water-mediated interchain hydrogen bonds than in the related Gly -> Ala
      structure. These could partly explain the difference in thermal stability between
      the different interruptions. In addition, our structures provide a detailed view
      of the dynamic property of such an interrupted zone with respect to hydrogen
      bonding topology, torsion angles, and helical parameters. Our results, for the
      first time, also identified the binding of zinc to the end of the triple helix.
      These findings will shed light on how the interruption sequence influences the
      conformation of the collagen molecule and provide a structural basis for further
      functional studies.

PMID- 29376321
TI  - Assessing Soil Contamination Due to Oil and Gas Production Using Vegetation
      Hyperspectral Reflectance.
AB  - The remote assessment of soil contamination remains difficult in vegetated areas.
      Recent advances in hyperspectral spectroscopy suggest making use of plant
      reflectance to monitor oil and gas leakage from industrial facilities. However,
      knowledge about plant response to oil contamination is still limited, so only
      very few imaging applications are possible at this stage. We therefore conducted
      a greenhouse experiment on three species long-term exposed to either oil
      contaminated or water-deficient soils. Reflectance measurements were regularly
      performed at leaf and plant scale over 61 days of exposure. Results showed an
      increase of reflectance in the visible (VIS), the red-edge and the short-wave
      infrared (SWIR) under both oil and water-deficit stress exposure. A contrasted
      response in the near-infrared (NIR) was also observed among species. Spectra
      underwent transformations to discriminate species' responses to the different
      treatments using linear discriminant analysis (LDA) with a stepwise procedure.
      Original and transformed spectra enabled to discriminate the plants' responses to
      the different treatments without confusion after 61 days. The discriminating
      wavelengths were consistent with the spectral differences observed. These results
      suggest differential changes in plant pigments, structure and water content as a
      response to various stressors, and open up promising perspectives for airborne
      and satellite applications.

PMID- 29376322
TI  - Self-Assembled Peptide-Lanthanide Nanoclusters for Safe Tumor Therapy: Overcoming
      and Utilizing Biological Barriers to Peptide Drug Delivery.
AB  - Developing a sophisticated nanomedicine platform to deliver therapeutics
      effectively and safely into tumor/cancer cells remains challenging in the field
      of nanomedicine. In particular, reliable peptide drug delivery systems capable of
      overcoming biological barriers are still lacking. Here, we developed a simple,
      rapid, and robust strategy to manufacture nanoclusters of ~90 nm in diameter that
      are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer
      peptides with different targets (BIM and PMI), and one cyclic peptide iNGR
      targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR)
      enhanced the resistance of peptide drugs to proteolysis, disassembled in response
      to reductive conditions that are present in the tumor microenvironment and
      inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR
      exhibited extremely low systemic toxicity and side effects in vivo. Thus, the
      peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for
      safe, targeted, and efficient peptide drug delivery in cancer therapy.

PMID- 29376323
TI  - In Situ Monitoring of Pb2+ Leaching from the Galvanic Joint Surface in a Prepared
      Chlorinated Drinking Water.
AB  - A novel method using a micro-ion-selective electrode (micro-ISE) technique was
      developed for in situ lead monitoring at the water-metal interface of a brass
      leaded solder galvanic joint in a prepared chlorinated drinking water
      environment. The developed lead micro-ISE (100 MUm tip diameter) showed excellent
      performance toward soluble lead (Pb2+) with sensitivity of 22.2 +/- 0.5 mV decade
      1 and limit of detection (LOD) of 1.22 * 10-6 M (0.25 mg L-1). The response time
      was less than 10 s with a working pH range of 2.0-7.0. Using the lead micro-ISE,
      lead concentration microprofiles were measured from the bulk to the metal surface
      (within 50 MUm) over time. Combined with two-dimensional (2D) pH mapping, this
      work clearly demonstrated that Pb2+ ions build-up across the lead anode surface
      was substantial, nonuniform, and dependent on local surface pH. A large pH
      gradient (DeltapH = 6.0) developed across the brass and leaded-tin solder joint
      coupon. Local pH decreases were observed above the leaded solder to a pH as low
      as 4.0, indicating it was anodic relative to the brass. The low pH above the
      leaded solder supported elevated lead levels where even small local pH
      differences of 0.6 units (DeltapH = 0.6) resulted in about four times higher
      surface lead concentrations (42.9 vs 11.6 mg L-1) and 5 times higher fluxes (18.5
      * 10-6 vs 3.5 * 10-6 mg cm-2 s-1). Continuous surface lead leaching monitoring
      was also conducted for 16 h.

PMID- 29376324
TI  - Turning the Spotlight on Lipids in Non-Apoptotic Cell Death.
AB  - Although apoptosis has long dominated the spotlight, studies in the past two
      decades have expanded the repertoire of programmed cell death (PCD). Several
      forms of non-apoptotic regulated cell death have been identified, with important
      links to organismal homeostasis and different disease pathologies. Necroptosis,
      ferroptosis, pyroptosis, and NETosis are the major forms of PCD that have
      attracted attention. Clear biochemical distinctions differentiate these forms of
      non-apoptotic PCD at the protein and membrane levels. For instance, pore
      formation at the plasma membrane is a hallmark of necroptosis and pyroptosis;
      however, different proteins facilitate pore formation in these processes. Here,
      we will highlight the role of lipids in different forms of non-apoptotic PCD. In
      particular, we discuss how lipids can trigger or facilitate the membrane-related
      changes that result in cell death. We also highlight the use of small molecules
      in elucidating the mechanisms of non-apoptotic PCD and the potential of lipid
      biosynthetic pathways to perturb these processes for therapeutic applications as
      a future avenue of research.

PMID- 29376325
TI  - Carboxyl-Photo-Reactive MS-Cleavable Cross-Linkers: Unveiling a Hidden Aspect of
      Diazirine-Based Reagents.
AB  - A major challenge in cross-linking/mass spectrometry (MS) is targeting carboxyl
      functions in proteins under physiological conditions that do not disturb the
      protein's conformation. Cross-linking of glutamic acid and aspartic acid residues
      in proteins will greatly expand the scope of structural mass spectrometry. We
      discovered that carboxyl-reactive cross-linkers have already been employed for
      many years in cross-linking/MS studies, yet in a completely different context.
      Diazirine-based cross-linkers, such as photomethionine and succinimidyldiazirine
      cross-linkers, are currently considered to react nonspecifically upon UV-A
      photoactivation with all 20 proteinogenic amino acids through a reactive carbene
      that inserts mainly into C-H bonds. We discovered that the cross-linking
      capability of diazirines based on X-H (X = C, N, O) insertion is in fact only the
      tip of the iceberg. Diazirines isomerize to linear diazo compounds that can react
      with carboxylic acids to yield esters. On top of that, the resulting cross-linked
      products are MS-cleavable allowing an automated analysis of cross-links via
      customized software tools. Therefore, diazirines open an entirely new route for
      photo-cross-linking of carboxylic acids. Previous cross-linking studies using
      diazirines have to be revisited in the light of these findings.

PMID- 29376327
TI  - Highly Efficient and Stable Strain-Release Radioiodination for Thiol
      Chemoselective Bioconjugation.
AB  - We report a novel thiol selective radioiodination method based on strain-release
      reaction. A new heterobifunctional radioiodination agent which has very good
      thiol selectivity and excellent stability with high radiolabeling yield was
      synthesized, characterized, and applied successfully for thiol-contained peptide
      labeling.

PMID- 29376328
TI  - Influences of Temperature and Metal on Subcritical Hydrothermal Liquefaction of
      Hyperaccumulator: Implications for the Recycling of Hazardous Hyperaccumulators.
AB  - Waste Sedum plumbizincicola, a zinc (Zn) hyperaccumulator during
      phytoremediation, was recycled via a subcritical hydrothermal liquefaction (HTL)
      reaction into multiple streams of products, including hydrochar, bio-oil, and
      carboxylic acids. Results show approximately 90% of Zn was released from the S.
      plumbizincicola biomass during HTL at an optimized temperature of 220  degrees C,
      and the release risk was mitigated via HTL reaction for hydrochar production. The
      low-Zn hydrochar (~200 mg/kg compared to original plant of 1558 mg/kg) was
      further upgraded into porous carbon (PC) with high porosity (930 m2/g) and
      excellent capability of carbon dioxide (CO2) capture (3 mmol/g). The porosity,
      micropore structure, and graphitization degree of PCs were manipulated by the
      thermal recalcitrance of hydrochar. More importantly, results showed that the
      released Zn2+ could effectively promote the production of acetic acid via the
      oxidation of furfural (FF) and 5-(hydroxymethyl)-furfural (HMF). Fourier
      transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with negative
      electrospray ionization analysis confirmed the deoxygenation and depolymerization
      reactions and the production of long chain fatty acids during HTL reaction of S.
      plumbizincicola. This work provides a new path for the recycling of waste
      hyperaccumulator biomass into value-added products.

PMID- 29376326
TI  - Design and Application of Sensors for Chemical Cytometry.
AB  - The bulk cell population response to a stimulus, be it a growth factor or a
      cytotoxic agent, neglects the cell-to-cell variability that can serve as a friend
      or as a foe in human biology. Biochemical variations among closely related cells
      furnish the basis for the adaptability of the immune system but also act as the
      root cause of resistance to chemotherapy by tumors. Consequently, the ability to
      probe for the presence of key biochemical variables at the single-cell level is
      now recognized to be of significant biological and biomedical impact. Chemical
      cytometry has emerged as an ultrasensitive single-cell platform with the
      flexibility to measure an array of cellular components, ranging from metabolite
      concentrations to enzyme activities. We briefly review the various chemical
      cytometry strategies, including recent advances in reporter design, probe and
      metabolite separation, and detection instrumentation. We also describe strategies
      for improving intracellular delivery, biochemical specificity, metabolic
      stability, and detection sensitivity of probes. Recent applications of these
      strategies to small molecules, lipids, proteins, and other analytes are
      discussed. Finally, we assess the current scope and limitations of chemical
      cytometry and discuss areas for future development to meet the needs of single
      cell research.

PMID- 29376329
TI  - Polyethylene Glycol-Engrafted Graphene Oxide as Biocompatible Materials for
      Peptide Nucleic Acid Delivery into Cells.
AB  - Graphene oxide (GO) is known to strongly bind single-stranded nucleic acids with
      fluorescence quenching near the GO surface. However, GO exhibits weak
      biocompatibility characteristics, such as low dispersibility in cell culture
      media and significant cytotoxicity. To improve dispersibility in cell culture
      media and cell viability of GO, we prepared nanosized GO (nGO) constructs and
      modified the nGO surface using polyethylene glycol (PEG-nGO). Single-stranded
      peptide nucleic acid (PNA) was adsorbed onto the PEG-nGO and was readily desorbed
      by adding complementary RNA or under low pH conditions. PNA adsorbed on the PEG
      nGO was efficiently delivered into lung cancer cells via endocytosis without
      affecting cell viability. Furthermore, antisense PNA delivered using PEG-nGO
      effectively downregulated the expression of the target gene in cancer cells. Our
      results suggest that PEG-nGO is a biocompatible carrier useful for PNA delivery
      into cells and serves as a promising gene delivery tool.

PMID- 29376330
TI  - Self-Formed Hybrid Interphase Layer on Lithium Metal for High-Performance Lithium
      Sulfur Batteries.
AB  - Lithium-sulfur (Li-S) batteries are promising candidates for high-energy storage
      devices due to high theoretical capacities of both the sulfur cathode and lithium
      (Li) metal anode. Considerable efforts have been devoted to improving sulfur
      cathodes. However, issues associated with Li anodes, such as low Coulombic
      efficiency (CE) and growth of Li dendrites, remain unsolved due to unstable solid
      electrolyte interphase (SEI) and lead to poor capacity retention and a short
      cycling life of Li-S batteries. In this work, we demonstrate a facile and
      effective approach to fabricate a flexible and robust hybrid SEI layer through co
      deposition of aromatic-based organosulfides and inorganic Li salts using
      poly(sulfur-random-1,3-diisopropenylbenzene) as an additive in an electrolyte.
      The aromatic-based organic components with planar backbone conformation and pi-pi
      interaction in the SEI layers can improve the toughness and flexibility to
      promote stable and high efficient Li deposition/dissolution. The as-formed
      durable SEI layer can inhibit dendritic Li growth, enhance Li
      deposition/dissolution CE (99.1% over 420 cycles), and in turn enable Li-S
      batteries with good cycling stability (1000 cycles) and slow capacity decay. This
      work demonstrates a route to address the issues associated with Li metal anodes
      and promote the development of high-energy rechargeable Li metal batteries.

PMID- 29376331
TI  - Nanoscale Titanium Dioxide (nTiO2) Transport in Natural Sediments: Importance of
      Soil Organic Matter and Fe/Al Oxyhydroxides.
AB  - Many engineered nanoparticle (ENP) transport experiments use quartz sand as the
      transport media; however, sediments are complex in nature, with heterogeneous
      compositions that may influence transport. Nanoscale titanium dioxide (nTiO2)
      transport in water-saturated columns of quartz sand and variations of a natural
      sediment was studied, with the objective of understanding the influence of soil
      organic matter (SOM) and Fe/Al-oxyhydroxides and identifying the underlying
      mechanisms. Results indicated nTiO2 transport was strongly influenced by pH and
      sediment composition. When influent pH was 5, nTiO2 transport was low because
      positively charged nTiO2 was attracted to negatively charged minerals and SOM.
      nTiO2 transport was slightly enhanced in sediments with sufficient SOM
      concentrations due to leached dissolved organic matter (DOM), which adsorbed onto
      the nTiO2 surface, reversing the zeta potential to negative. When influent pH was
      9, nTiO2 transport was generally high because negatively charged medium repelled
      negatively charged nTiO2. However, in sediments with SOM or amorphous Fe/Al
      oxyhydroxides depleted, transport was low due to pH buffering by the sediments,
      causing attraction between nTiO2 and crystalline Fe oxyhydroxides. This was
      counteracted by DOM adsorbing to nTiO2, stabilizing it in suspension. Our
      research demonstrates the importance of SOM and Fe/Al oxyhydroxides in governing
      ENP transport in natural sediments.

PMID- 29376332
TI  - Three-Dimensional Free Chlorine and Monochloramine Biofilm Penetration:
      Correlating Penetration with Biofilm Activity and Viability.
AB  - Disinfectant biofilm penetration and its effect on biofilm aerobic activity and
      viability are still unclear. In this study, free chlorine and monochloramine were
      applied until full biofilm penetration occurred, and their effects on biofilm
      aerobic activity and viability were investigated in three dimensions throughout
      the entire biofilm depth, extending previous work where viability analysis was
      limited to the upper biofilm (50 MUm depth), free chlorine penetration did not
      reach completion, and only one-dimensional (depth) profiles were obtained. The
      free chlorine and monochloramine biofilm concentration profiles were correlated
      spatially and temporally with aerobic microbial activity and cell-membrane
      integrity based viability using a combination of (1) microelectrode measurements
      for disinfectant penetration and (2) LIVE/DEAD BacLight staining, cryo-cross
      sectioning, and confocal micrographs analysis for viability measurements
      throughout the entire biofilm depth. Compared to monochloramine, free chlorine
      penetration (1) was slower, (2) led to a greater decrease in biofilm thickness
      from sloughing, and (3) corresponded directly with a viability decrease. In
      addition, biofilm heterogeneity led to minor differences in either disinfectant's
      biofilm penetration, and prior biofilm exposure to monochloramine provided little
      impact to subsequent free chlorine biofilm penetration.

PMID- 29376333
TI  - Chemical Analysis of Complex Surface-Adsorbed Molecules and Their Reactions by
      Means of Cluster-Induced Desorption/Ionization Mass Spectrometry.
AB  - Desorption/ionization induced by neutral SO2 clusters (DINeC) is used for mass
      spectrometry (MS) of surface-adsorbed molecules. The method is shown to be a
      surface-sensitive analysis tool capable of detecting molecular adsorbates in a
      wide range of molecular weights as well as their reactions on surfaces, which are
      otherwise difficult to access. Two different surface/adsorbate systems prepared
      by means of electrospray ion beam deposition (ES-IBD) were investigated: For the
      peptide angiotensin II on gold, intact molecules were desorbed from the surface
      when deposited by soft landing ES-IBD. By comparison to the well-controlled
      amount of substance deposited by ES-IBD, the sensitivity of DINeC-MS was shown to
      be on the order of 0.1% of a monolayer coverage, corresponding to femtomoles of
      analyte. Depending on deposition and sample conditions, the original state of
      charge of the molecules could be retrieved. Reaction of the adsorbed molecules
      both with surface atoms as well as with coadsorbed D2O was monitored. Rhodamine
      6G was also desorbed as an intact molecule when deposited with kinetic energies
      below 50 eV. For higher deposition energy, fragmentation of the dye molecules was
      observed by means of DINeC-MS.

PMID- 29376334
TI  - Kinetics of Methylmercury Production Revisited.
AB  - Laboratory measurements of the biologically mediated methylation of mercury (Hg)
      to the neurotoxin monomethylmercury (MMHg) often exhibit kinetics that are
      inconsistent with first-order kinetic models. Using time-resolved measurements of
      filter passing Hg and MMHg during methylation/demethylation assays, a multisite
      kinetic sorption model, and reanalyses of previous assays, we show that competing
      kinetic sorption reactions can lead to time-varying availability and apparent non
      first-order kinetics in Hg methylation and MMHg demethylation. The new model
      employing a multisite kinetic sorption model for Hg and MMHg can describe the
      range of behaviors for time-resolved methylation/demethylation data reported in
      the literature including those that exhibit non-first-order kinetics.
      Additionally, we show that neglecting competing sorption processes can confound
      analyses of methylation/demethylation assays, resulting in rate constant
      estimates that are systematically biased low. Simulations of MMHg production and
      transport in a hypothetical periphyton biofilm bed illustrate the implications of
      our new model and demonstrate that methylmercury production may be significantly
      different than projected by single-rate first-order models.

PMID- 29376335
TI  - Perfluoroalkyl Acids Including Isomers in Tree Barks from a Chinese
      Fluorochemical Manufacturing Park: Implication for Airborne Transportation.
AB  - Measurement of airborne perfluoroalkyl acids (PFAAs) is challenging, but
      important for understanding their atmospheric transport. Tree bark is good media
      for monitoring semivolatile compounds in the atmosphere. Whether it could work as
      an indicator of airborne PFAAs was first examined in this study. Bark and leaf
      samples collected around a Chinese fluorochemical manufacturing park (FMP) were
      analyzed for PFAAs and their branched isomers. Total PFAA concentrations (?PFAAs)
      in the bark (mean, 279 ng/g dw) and leaf (250 ng/g dw) samples were comparable.
      ?PFAAs in the barks collected within the boundaries of the FMP were significantly
      (p < 0.05) higher than those outside the FMP, and displayed a decreasing spatial
      trend as the distance from the FMP increased. However, such spatial difference
      and trend were not observed for the leaves. PFAA compositional profiles in most
      of the tree barks were consistent with each other, but different from those in
      tree leaves. These results indicated that tree barks mainly accumulated airborne
      PFAAs, while uptake from soil and translocation could make partial contribution
      to those in leaves. Perfluorooctanoate and perfluorooctanesulfonate in barks had
      strictly consistent isomeric compositions with their electrochemical fluorination
      products. Overall, these results indicated that the bark could be a good
      indicator of airborne PFAAs with respect to their occurrence, isomeric signature,
      and atmospheric transport.

PMID- 29376336
TI  - Comprehensive Analysis of the Great Lakes Top Predator Fish for Novel Halogenated
      Organic Contaminants by GC*GC-HR-ToF Mass Spectrometry.
AB  - The U.S. Environmental Protection Agency's Great Lakes Fish Monitoring and
      Surveillance Program (GLFMSP) has traced the fate and transport of anthropogenic
      chemicals in the Great Lakes region for decades. Isolating and identifying
      halogenated species in fish is a major challenge due to the complexity of the
      biological matrix. A nontargeted screening methodology was developed and applied
      to lake trout using a 2-dimensional gas chromatograph coupled to a high
      resolution time-of-flight mass spectrometer (GC*GC-HR-ToF MS). Halogenated
      chemicals were identified using a combination of authentic standards and library
      spectral matching, with molecular formula estimations provided by exact mass
      spectral interpretation. In addition to the halogenated chemicals currently being
      targeted by the GLFMSP, more than 60 nontargeted halogenated species were
      identified. Most appear to be metabolites or breakdown products of larger
      halogenated organics. The most abundant compound class was halomethoxyphenols
      accounting for more than 60% of the total concentration of halogenated compounds
      in top predator fish from all five Great Lakes illustrating the need and utility
      of nontargeted halogenated screening of aquatic systems using this platform.

PMID- 29376337
TI  - Increasing Analytical Separation and Duty Cycle with Nonlinear Analytical
      Mobility Scan Functions in TIMS-FT-ICR MS.
AB  - In this work, nonlinear, stepping analytical mobility scan functions are
      implemented to increase the analytical separation and duty cycle during tandem
      Trapped Ion Mobility Spectrometry and FT-ICR MS operation. The differences
      between linear and stepping scan functions are described based on length of
      analysis, mobility scan rate, signal-to-noise, and mobility resolving power.
      Results showed that for the linear mobility scan function only a small fraction
      of the scan is sampled, resulting in the lowest duty cycle 0.5% and longest
      experiment times. Implementing nonlinear targeted scan functions for analysis of
      known mobilities resulted in increased duty cycle (0.85%) and resolving powers (R
      up to 300) with a 6-fold reduction in time from 30 to 5 min. For broad range
      characterization, a nonlinear mobility stepping scan function provided the best
      sensitivity, resolving power, duty cycle (4%), and points per peak. The
      applicability of nonlinear mobility scan functions for the analysis of complex
      mixtures is illustrated for the case of a direct infusion of a MCF-7 breast
      cancer cell digest, where isobaric peptides (e.g., DFTPAELR and TTILQSTGK) were
      separated in the mobility domain (RIMS: 110) and identified based on their CCS,
      accurate mass (RMS: 550k), and tandem MS using IRMPD in the ICR cell.

PMID- 29376338
TI  - Enhancing Membrane Protein Identification Using a Simplified Centrifugation and
      Detergent-Based Membrane Extraction Approach.
AB  - Membrane proteins may act as transporters, receptors, enzymes, and adhesion
      anchors, accounting for nearly 70% of pharmaceutical drug targets. Difficulties
      in efficient enrichment, extraction, and solubilization still exist because of
      their relatively low abundance and poor solubility. A simplified membrane protein
      extraction approach with advantages of user-friendly sample processing
      procedures, good repeatability and significant effectiveness was developed in the
      current research for enhancing enrichment and identification of membrane
      proteins. This approach combining centrifugation and detergent along with LC
      MS/MS successfully identified higher proportion of membrane proteins, integral
      proteins and transmembrane proteins in membrane fraction (76.6%, 48.1%, and
      40.6%) than in total cell lysate (41.6%, 16.4%, and 13.5%), respectively.
      Moreover, our method tended to capture membrane proteins with high degree of
      hydrophobicity and number of transmembrane domains as 486 out of 2106 (23.0%) had
      GRAVY > 0 in membrane fraction, 488 out of 2106 (23.1%) had TMs >= 2. It also
      provided for improved identification of membrane proteins as more than 60.6% of
      the commonly identified membrane proteins in two cell samples were better
      identified in membrane fraction with higher sequence coverage. Data are available
      via ProteomeXchange with identifier PXD008456.

PMID- 29376339
TI  - Discovering Putative Peptides Encoded from Noncoding RNAs in Ribosome Profiling
      Data of Arabidopsis thaliana.
AB  - Most noncoding RNAs are considered by their expression at low levels and as
      having a limited phylogenetic distribution in the cytoplasm, indicating that they
      may be only involved in specific biological processes. However, recent studies
      showed the protein-coding potential of ncRNAs, indicating that they might be a
      source of some special proteins. Although there are increasing noncoding RNAs
      identified to be able to code proteins, it is challenging to distinguish coding
      RNAs from previously annotated ncRNAs, and to detect the proteins from their
      translation. In this article, we designed a pipeline to identify these noncoding
      RNAs in Arabidopsis thaliana from three NCBI GEO data sets with coding potential
      and predict their translation products. 31 311 noncoding RNAs were predicted to
      be translated into peptides, and they showed lower conservation rate than common
      proteins. In addition, we built an interaction network between these peptides and
      annotated Arabidopsis proteins using BIPS, which included 69 peptides from
      noncoding RNAs. Peptides in the interaction network showed different
      characteristics from other noncoding RNA-derived peptides, and they participated
      in several crucial biological processes, such as photorespiration and stress
      responses. All the information of putative ncPEPs and their interaction with
      proteins predicted above are finally integrated in a database, PncPEPDB (
      http://bis.zju.edu.cn/PncPEPDB ). These results showed that peptides derived from
      noncoding RNAs may play important roles in noncoding RNA regulation, which
      provided another hypothesis that noncoding RNA may regulate the metabolism via
      their translation products.

PMID- 29376340
TI  - Repeatable Photodynamic Therapy with Triggered Signaling Pathways of Fibroblast
      Cell Proliferation and Differentiation To Promote Bacteria-Accompanied Wound
      Healing.
AB  - Despite the development of advanced antibacterial materials, bacterial infection
      is still a serious problem for wound healing because it usually induces severe
      complications and cannot be eradicated completely. Most current materials cannot
      simultaneously provide antibacterial activity, reusability, and biocompatibility
      as well as participate in stimulating cell behaviors to promote bacteria
      accompanied wound healing. This work fabricated a hybrid hydrogel embedded with
      two-dimensional (2D) few-layer black phosphorus nanosheets (BPs) via simple
      electrostatic interaction. Within 10 min, 98.90% Escherichia coli and 99.51%
      Staphylococcus aureus can be killed rapidly by this hybrid, due to its powerful
      ability to produce singlet oxygen (1O2) under simulated visible light. In
      addition, this hydrogel also shows a high repeatability; that is, the
      antibacterial efficacy can still reach up to 95.6 and 94.58% against E. coli and
      S. aureus, respectively, even after challenging bacteria up to four times
      repeatedly. In vitro and in vivo results reveal that BPs in this hybrid hydrogel
      can promote the formation of the fibrinogen at the early stages during the tissue
      reconstruction process for accelerated incrustation. In addition, BPs can also
      trigger phosphoinositide 3-kinase (PI3K), phosphorylation of protein kinase B
      (Akt), and extracellular signal-regulated kinase (ERK1/2) signaling pathways for
      enhanced cellular proliferation and differentiation. Moreover, the hydrogel
      causes no appreciable abnormalities or damage to major organs (heart, liver,
      spleen, lung, and kidney) in rats during the wound healing process. Therefore,
      this BP-based hydrogel will have great potential as a safe multimodal therapeutic
      system for active wound healing and sterilization.

PMID- 29376341
TI  - Occurrence of Organophosphorus Flame Retardants and Plasticizers (PFRs) in
      Belgian Foodstuffs and Estimation of the Dietary Exposure of the Adult
      Population.
AB  - The occurrence of 14 organophosphorus flame retardants and plasticizers (PFRs)
      was investigated in 165 composite food samples purchased from the Belgian market
      and divided into 14 food categories, including fish, crustaceans, mussels, meat,
      milk, cheese, dessert, food for infants, fats and oils, grains, eggs, potatoes
      and derived products, other food (stocks), and vegetables. Seven PFRs [namely,
      tri-n-butyl phosphate (TnBP), tris(2-chloroethyl) phosphate (TCEP), tris(1-chloro
      2-propyl) phosphate (TCIPP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP),
      triphenyl phosphate (TPHP), 2-ethylhexyldiphenyl phosphate (EHDPHP), and tris(2
      ethylhexyl) phosphate (TEHP)] were detected at concentrations above
      quantification limits. Fats and oils were the most contaminated category, with a
      total PFR concentration of 84.4 ng/g of wet weight (ww), followed by grains (36.9
      ng/g of ww) and cheese (20.1 ng/g of ww). Our results support the hypothesis that
      PFR contamination may occur during industrial processing and manipulation of food
      products (e.g., packaging, canning, drying, etc.). Considering the daily average
      intake of food for the modal adult Belgian (15-64 years of age), the dietary
      exposure to sum PFRs was estimated to be <=7500 +/- 1550 ng/day [103 +/- 21 ng/kg
      of body weight (bw)/day]. For individual PFRs, TPHP contributed on average 3400
      ng/day (46.6 ng/kg of bw/day), TCIPP 1350 ng/day (18.5 ng/kg of bw/day), and
      EHDPHP 1090 ng/day (15 ng/kg of bw/day), values that were lower than their
      corresponding health-based reference doses. The mean dietary exposure mainly
      originated from grains (39%), followed by fats and oils (21%) and dairy products
      (20%). No significant differences between the intakes of adult men and women were
      observed.

PMID- 29376342
TI  - Active Control of Inertial Focusing Positions and Particle Separations Enabled by
      Velocity Profile Tuning with Coflow Systems.
AB  - Inertial microfluidics has drawn much attention not only for its diverse
      applications but also for counterintuitive new fluid dynamic behaviors. Inertial
      focusing positions are determined by two lift forces, that is, shear gradient and
      wall-induced lift forces, that are generally known to be opposite in direction in
      the flow through a channel. However, the direction of shear gradient lift force
      can be reversed if velocity profiles are shaped properly. We used coflows of two
      liquids with different viscosities to produce complex velocity profiles that lead
      to inflection point focusing and alteration of inertial focusing positions; the
      number and the locations of focusing positions could be actively controlled by
      tuning flow rates and viscosities of the liquids. Interestingly, 3-inlet coflow
      systems showed focusing mode switching between inflection point focusing and
      channel face focusing depending on Reynolds number and particle size. The
      focusing mode switching occurred at a specific size threshold, which was easily
      adjustable with the viscosity ratio of the coflows. This property led to
      different-sized particles focusing at completely different focusing positions and
      resulted in highly efficient particle separation of which the separation
      threshold was tunable. Passive separation techniques, including inertial
      microfluidics, generally have a limitation in the control of separation
      parameters. Coflow systems can provide a simple and versatile platform for active
      tuning of velocity profiles and subsequent inertial focusing characteristics,
      which was demonstrated by active control of the focusing mode using viscosity
      ratio tuning and temperature changes of the coflows.

PMID- 29376343
TI  - Mesophase Formation Stabilizes High-Purity Magic-Sized Clusters.
AB  - Magic-sized clusters (MSCs) are renowned for their identical size and closed
      shell stability that inhibit conventional nanoparticle (NP) growth processes.
      Though MSCs have been of increasing interest, understanding the reaction pathways
      toward their nucleation and stabilization is an outstanding issue. In this work,
      we demonstrate that high concentration synthesis (1000 mM) promotes a well
      defined reaction pathway to form high-purity MSCs (>99.9%). The MSCs are
      resistant to typical growth and dissolution processes. On the basis of insights
      from in situ X-ray scattering analysis, we attribute this stability to the
      accompanying production of a large (>100 nm grain size), hexagonal organic
      inorganic mesophase that arrests growth of the MSCs and prevents NP growth. At
      intermediate concentrations (500 mM), the MSC mesophase forms, but is unstable,
      resulting in NP growth at the expense of the assemblies. These results provide an
      alternate explanation for the high stability of MSCs. Whereas the conventional
      mantra has been that the stability of MSCs derives from the precise arrangement
      of the inorganic structures (i.e., closed-shell atomic packing), we demonstrate
      that anisotropic clusters can also be stabilized by self-forming fibrous
      mesophase assemblies. At lower concentration (<200 mM or >16 acid-to-metal), MSCs
      are further destabilized and NPs formation dominates that of MSCs. Overall, the
      high concentration approach intensifies and showcases inherent concentration
      dependent surfactant phase behavior that is not accessible in conventional (i.e.,
      dilute) conditions. This work provides not only a robust method to synthesize,
      stabilize, and study identical MSC products but also uncovers an underappreciated
      stabilizing interaction between surfactants and clusters.

PMID- 29376344
TI  - Highly Stable Spherical Metallo-Capsule from a Branched Hexapodal Terpyridine and
      Its Self-Assembled Berry-type Nanostructure.
AB  - Discrete spherical metallo-organic capsules at the nanometer scale, especially
      those constructed from unique building blocks, have received significant
      attention recently because of their fascinating molecular aesthetics and
      potential applications due to their compact cavities. Here, the synthesis and
      characterization of a hexapodal, branched terpyridine ligand are presented along
      with the nearly quantitative self-assembly of the resulting tetrameric metallo
      nanosphere. This metallo-nanosphere exhibited four quasi-triangular and six
      rhombus-like facets, all of which were made by the same hook-like bis
      terpyridine. Collision-induced dissociation experiments were done to investigate
      overall stability. The metallo-architecture and host-guest chemistry were
      investigated with coronene and fully characterized by 1D and 2D NMR, ESI-MS, and
      transmission electron microscopy. Furthermore, this metallo-nanosphere was
      observed to hierarchically self-assemble into berry-type structures in an
      acetonitrile/methanol mixture, by virtue of counterion-mediated attractions. The
      functional molecular metallo-nanosphere presented here expands the reach of
      terpyridine coordination systems into molecular containers and other model
      systems.

PMID- 29376345
TI  - Synthesis of Hollow Biomineralized CaCO3-Polydopamine Nanoparticles for
      Multimodal Imaging-Guided Cancer Photodynamic Therapy with Reduced Skin
      Photosensitivity.
AB  - The development of activatable nanoplatforms to simultaneously improve diagnostic
      and therapeutic performances while reducing side effects is highly attractive for
      precision cancer medicine. Herein, we develop a one-pot, dopamine-mediated
      biomineralization method using a gas diffusion procedure to prepare calcium
      carbonate-polydopamine (CaCO3-PDA) composite hollow nanoparticles as a
      multifunctional theranostic nanoplatform. Because of the high sensitivity of such
      nanoparticles to pH, with rapid degradation under a slightly acidic environment,
      the photoactivity of the loaded photosensitizer, i.e., chlorin e6 (Ce6), which is
      quenched by PDA, is therefore increased within the tumor under reduced pH,
      showing recovered fluorescence and enhanced singlet oxygen generation. In
      addition, due to the strong affinity between metal ions and PDA, our
      nanoparticles can bind with various types of metal ions, conferring them with
      multimodal imaging capability. By utilizing pH-responsive multifunctional
      nanocarriers, effective in vivo antitumor photodynamic therapy (PDT) can be
      realized under the precise guidance of multimodal imaging. Interestingly, at
      normal physiological pH, our nanoparticles are quenched and show much lower
      phototoxicity to normal tissues, thus effectively reducing skin damage during
      PDT. Therefore, our work presents a unique type of biomineralized theranostic
      nanoparticles with inherent biocompatibility, multimodal imaging functionality,
      high antitumor PDT efficacy, and reduced skin phototoxicity.

PMID- 29376346
TI  - Synthesis of Prebiotic Caramels Catalyzed by Ion-Exchange Resin Particles:
      Kinetic Model for the Formation of Di-d-fructose Dianhydrides.
AB  - Caramel enriched in di-d-fructose dianhydrides (DFAs, a family of prebiotic
      cyclic fructodisaccharides) is a functional food with beneficial properties for
      health. The aim of this work was to study the conversion of fructose into DFAs
      catalyzed by acid ion-exchange resin, in order to establish a simplified
      mechanism of the caramelization reaction and a kinetic model for DFA formation.
      Batch reactor experiments were carried out in a 250 mL spherical glass flask and
      afforded up to 50% DFA yields. The mechanism proposed entails order 2 reactions
      that describe fructose conversion on DFAs or formation of byproducts such as HMF
      or melanoidines. A third order 1 reaction defines DFA transformation into
      fructosyl-DFAs or fructo-oligosaccharides. The influence of fructose
      concentration, resin loading and temperature was studied to calculate the kinetic
      parameters necessary to scale up the process.

PMID- 29376347
TI  - Comparisons of Protein Dynamics from Experimental Structure Ensembles, Molecular
      Dynamics Ensembles, and Coarse-Grained Elastic Network Models.
AB  - Predicting protein motions is important for bridging the gap between protein
      structure and function. With growing numbers of structures of the same or closely
      related proteins becoming available, it is now possible to understand more about
      the intrinsic dynamics of a protein with principal component analysis (PCA) of
      the motions apparent within ensembles of experimental structures. In this paper,
      we compare the motions extracted from experimental ensembles of 50 different
      proteins with the modes of motion predicted by several types of coarse-grained
      elastic network models (ENMs) which additionally take into account more details
      of either the protein geometry or the amino acid specificity. We further compare
      the structural variations in the experimental ensembles with the motions sampled
      in molecular dynamics (MD) simulations for a smaller subset of 17 proteins with
      available trajectories. We find that the correlations between the motions
      extracted from MD trajectories and experimental structure ensembles are slightly
      different than those for the ENMs, possibly reflecting potential sampling biases.
      We find that there are small gains in the predictive power of the ENMs in
      reproducing motions present in either experimental or MD ensembles by accounting
      for the protein geometry rather than the amino acid specificity of the
      interactions.

PMID- 29376348
TI  - Hafnocene-based Bicyclo[2.1.1]hexene Germylenes - Formation, Reactivity, and
      Structural Flexibility.
AB  - 2,5-Disilylsubstituted germole dianions 1 react with hafnocene dichloride to give
      hafnocene-based bicyclo[2.1.1]hexene germylenes 3. Their formation proceeds via
      hafnocene-germylene complexes 2 that were identified by NMR and UV spectroscopy.
      Germylenes 3 are stabilized by homoconjugation between the empty 4p(Ge) orbital
      and the pi-bond of the innercyclic C2?C3 double bond. This interaction can be
      understood as sigma2, pi-coordination of the butadiene part to the dicoordinated
      germanium atom that leaves the 16e- hafnocene moiety electronically unsaturated.
      We demonstrate that this new class of germylenes might serve as ligand to a
      variety of low-valent transition-metal complexes. The structure of the germylene
      ligand in complexes with Fe(0), Ni(0), and Au(I) and in reaction products with N
      heterocyclic carbenes showed an intriguing structural flexibility that allows to
      accommodate different electronic situations at the ligating germanium atom. The
      origin of this structural adaptability is the interplay between the topological
      flexible unsaturated germanium ring and the hafnocene group.

PMID- 29376349
TI  - Mechanism of Fluorescence Quenching by Acylamino Twist in the Excited State for 1
      (Acylamino)anthraquinones.
AB  - Nitrogen-containing anthraquinone derivatives are widely applied in vegetable
      fiber dyes. In this paper, the fluorescence quenching mechanism by an acylamino
      group twist in the excited state for the 1-(acylamino)anthraquinones (AYAAQs)
      derivatives in acetonitrile is investigated by density functional theory (DFT)
      and time-dependent density functional theory (TD-DFT) methods. The calculated
      Stokes shift is in good agreement with the experimental data. The energy profiles
      show that each AYAAQs derivative reveals a barrierless twist process, indicating
      that the involvement of acylamino group rotation in addition to proton transfer
      becomes as another important coordinate in the excited state relaxation pathway.
      The effects of electron-substituted group promote twist process compared with 1
      aminoanthraquinone (AAQ). Then, the cross points are searched by the constructed
      linearly interpolated internal coordinate (LIIC) pathways for AYAAQs,
      demonstrating that the potential energy curves of the S1 and T2 states intersect
      each other and are in accord with the El-Sayed rules. So one can conclude that
      the acylamino group twist and following intersystem crossing (ISC) processes are
      important nonradiative inactivation channel for the S1 state of the AYAAQs
      derivatives, which is more prone to proton transfer process and can explain the
      low fluorescence efficiency. In addition, we have measured the phosphorescence
      spectra of AAQ, and on this basis, it can be predicted that the phosphorescence
      may occur for the AYAAQs derivatives.

PMID- 29376350
TI  - Measurement and Characterization of Hydrogen-Deuterium Exchange Chemistry Using
      Relaxation Dispersion NMR Spectroscopy.
AB  - One-dimensional heteronuclear relaxation dispersion NMR spectroscopy at 13C
      natural abundance successfully characterized the dynamics of the hydrogen
      deuterium exchange reaction occurring at the Nepsilon position in l-arginine by
      monitoring Cdelta in varying amounts of D2O. A small equilibrium isotope effect
      was observed and quantified, corresponding to DeltaG = -0.14 kcal mol-1. A
      bimolecular rate constant of kD = 5.1 * 109 s-1 M-1 was determined from the pH*
      dependence of kex (where pH* is the direct electrode reading of pH in 10% D2O and
      kex is the nuclear spin exchange rate constant), consistent with diffusion
      controlled kinetics. The measurement of DeltaG serves to bridge the millisecond
      time scale lifetimes of the detectable positively charged arginine species with
      the nanosecond time scale lifetime of the nonobservable low-populated neutral
      arginine intermediate species, thus allowing for characterization of the
      equilibrium lifetimes of the various arginine species in solution as a function
      of fractional solvent deuterium content. Despite the system being in fast
      exchange on the chemical shift time scale, the magnitude of the secondary isotope
      shift due to the exchange reaction at Nepsilon was accurately measured to be 0.12
      ppm directly from curve-fitting D2O-dependent dispersion data collected at a
      single static field strength. These results indicate that relaxation dispersion
      NMR spectroscopy is a robust and general method for studying base-catalyzed
      hydrogen-deuterium exchange chemistry at equilibrium.

PMID- 29376351
TI  - Effect of Transition Metal Fragments on the Reverse Fritsch-Buttenberg-Wiechell
      Type Ring Contraction Reaction of Metallabenzynes to Metal-Carbene Complexes.
AB  - Metallabenzynes (1M), contrary to their organic analogues, benzynes, undergo ring
      contraction to metal-carbene complexes (2M) via a reverse Fritsch-Buttenberg
      Wiechell (FBW) type rearrangement. A detailed computational quantum mechanical
      study has been carried out to understand the effect of different third row
      transition metal fragments (ML2L'2; M = W, Re, Os, Ir, Pt; L/L' = PH3, Cl, CO) on
      the stability of metallabenzynes and their reactivity toward reverse FBW type
      rearrangement. Our results indicate that the late transition metal fragments
      Ir(PH3)Cl3 and PtCl4 prefer 16 VE metal-carbene complex (2M), while the middle
      transition metal fragments W(PH3)4, Re(PH3)3Cl, and Os(PH3)2Cl2 prefer
      metallabenzyne (1M). This can be attributed to the reduced overlap between the
      transition metal fragment ML2L'2 and organic fragment C5H4 in metallabenzyne 1M
      when M changes from W to Pt. Furthermore, the presence of a pi-accepting ligand
      CO on the metal fragment makes the conversion of 1M to 2M more feasible.

PMID- 29376352
TI  - Mitotically Stable Modification of DNA Methylation in IGF2/H19 Imprinting Control
      Region Is Associated with Activated Hepatic IGF2 Expression in Offspring Rats
      from Betaine-Supplemented Dams.
AB  - The growth-promoting action of betaine involves activation of GH/IGF-1 signaling,
      yet it remains unclear whether insulin-like growth factor 2 (IGF2), an imprinting
      gene, is affected by maternal dietary betaine supplementation. In this study, F1
      offspring rats derived from dams fed basal or betaine-supplemented diet were
      examined at D21 and D63. Maternal betaine significantly upregulated the hepatic
      expression of IGF2 mRNA and protein in offspring rats at both D21 and D63, which
      was accompanied by enhanced hepatic IGF2 immunoreactivity and elevated serum IGF
      2 level. Higher protein expression of betaine-homocysteine methyltransferase and
      DNA methyltransferase 1 was detected in the betaine group at D21, but not D63.
      However, hypermethylation of the imprinting control region of the IGF2/H19 locus
      at D21 was maintained at D63. These results indicate that maternal betaine
      modifies DNA methylation of IGF2/H19 imprinting control region in a mitotically
      stable fasion, which was associated with the activation hepatic IGF2 expression
      in offspring rats.

PMID- 29376353
TI  - Ni-Catalyzed Site-Selective Dicarboxylation of 1,3-Dienes with CO2.
AB  - A site-selective catalytic incorporation of multiple CO2 molecules into 1,3
      dienes en route to adipic acids is described. This protocol is characterized by
      its mild conditions, excellent chemo- and regioselectivity and ease of execution
      under CO2 (1 atm), including the use of bulk butadiene and/or isoprene
      feedstocks.

PMID- 29376354
TI  - Ground- and Excited-State Interactions of a Psoralen Derivative with Human
      Telomeric G-Quadruplex DNA.
AB  - G-quadruplex DNA has been a recent target for anticancer agents, and its binding
      interactions with small molecules, often used as anticancer drugs, have become an
      important area of research. Considering that psoralens have long been studied in
      the context of duplex DNA but that very little is known about their potential as
      G-quadruplex binders and their excited-state interaction with the latter has not
      been explored, we have studied herein the binding of a planar water-soluble
      psoralen derivative, 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), with the 22
      mer human telomeric G-quadruplex-forming sequence, AGGG(TTAGGG)3, labeled here as
      (hTel22), and investigated the consequences of photoexcitation of AMT by
      calorimetric and spectroscopic techniques. The results show an enthalpy-driven
      1:1 binding of AMT with hTel22 via end-stacking mode. Fluorescence quenching
      experiments on 6-fluorescein amidite-labeled oligomers indicate that the binding
      site is nearer to the 3' end of hTel22 in the diagonal loop region. Femtosecond
      time-resolved transient absorption measurements indicate electron transfer from
      the guanine moiety of hTel22 to photoexcited AMT, leading to the formation of a
      radical pair species (AMT*-G*+), which survives for 30 ps and is favored by a
      parallel/quasi-parallel orientation between the two. The findings reveal
      psoralens as a prospective class of compounds for the development of anticancer
      therapeutics by targeting the G-quadruplex DNA.

PMID- 29376355
TI  - Systematic Characterization of Gas Phase Binary Pre-Nucleation Complexes
      Containing H2SO4 + X, [ X = NH3, (CH3)NH2, (CH3)2NH, (CH3)3N, H2O, (CH3)OH,
      (CH3)2O, HF, CH3F, PH3, (CH3)PH2, (CH3)2PH, (CH3)3P, H2S, (CH3)SH, (CH3)2S, HCl,
      (CH3)Cl)]. A Computational Study.
AB  - A systematic characterization of gas phase binary prenucleation complexes between
      H2SO4 (SA) and other molecules present in the atmosphere (NH3, (CH3)NH2,
      (CH3)2NH, (CH3)3N, H2O, (CH3)OH, (CH3)2O, HF, CH3 F, PH3, (CH3)PH2, (CH3)2PH,
      (CH3)3P, H2S, (CH3)SH, (CH3)2S, HCl, (CH3)Cl) has been carried out using the
      omegaB97X-D/6-311++(2d,2p) method at the DFT level of theory. A relationship
      between the energy gap of the SA's LUMO and the partner molecule's HOMO, and the
      increasing number of methyl groups -CH3 in the SA's partner molecule is provided.
      The binding energies of the bimolecular complexes are found to be related to the
      electron density in the hydrogen bond critical point, the HOMO-LUMO energy gap,
      the nature of the hydrogen acceptor atom, and the frequencies shift of acid OH
      bonds. The results show how the frontier orbital compatibility determines the
      binding energy and that the properties of SA's OH bond which remains free of
      interactions are affected by the bimolecular adduct formation.

PMID- 29376356
TI  - Effect of Basicity on the Hydrolysis of the Bi(III) Aqua Ion in Solution: An Ab
      Initio Molecular Dynamics Study.
AB  - Hydrolysis of the Bi(III) aqua ion under a range of solution conditions has been
      studied by means of ab initio molecular dynamics simulations. While the Bi(III)
      aqua ion is stable in pure water, there is an increasing degree of hydrolysis
      with the number of hydroxide anions in the medium. This is accompanied by a
      monotonic decrease of the total coordination number to an asymptotic value of ~6,
      reached under extreme basicity conditions. Comparison of the simulated Bi(III)
      hydrolyzed species with the experimental species distribution at different
      degrees of basicity suggests that, at the PBE/DFT level of theory here employed,
      liquid water shows an overly acidic character. Predictions of theoretical EXAFS
      and XANES spectra were generated from the AIMD trajectories for different Bi
      hydrolyzed species, [Bi(HO)m(H2O)n]3-m+, m = 0-3 and n = 7-2. Comparison with
      available experimental spectra is presented. Spectral features joined to the
      degree of hydrolysis and hydration are analyzed.

PMID- 29376357
TI  - Phosphinoyl Radical-Initiated 1,2-Bifunctional Thiocyanodiphenylphosphinoylation
      of Alkenes.
AB  - 1,2-Bifuctional thiocyanodiphenylphosphinoylation of alkenes is established
      through the phosphinoyl radical addition followed by Cu-catalyzed thiocyanation.
      This one-pot reaction is applicable to a range of aromatic, aliphatic, and cyclic
      alkenes to afford thiocyanodiphenylphosphinoylated compounds in satisfactory
      yields.

PMID- 29376358
TI  - Selective Synthesis of Divergolide I.
AB  - Divergolide I (1) is a naphthoquinone ansamycin that exhibits broad antibacterial
      activity. Its tetracyclic ring system is believed to be biosynthetically
      assembled via ring contraction of a macrocyclic precursor (proto-divergolide)
      that is both a macrolactone and a macrolactam. We here report a convergent and
      enantioselective synthesis that delivers the target molecule in less than 20
      linear steps. Our work establishes the absolute configuration of divergolide I,
      confirms its relative configuration, and demonstrates that the biomimetic
      cyclization of a proto-divergolide can be surprisingly selective.

PMID- 29376359
TI  - Role of Methyl-2-nitrophenol Photolysis as a Potential Source of OH Radicals in
      the Polluted Atmosphere: Implications from Laboratory Investigation.
AB  - Methyl-substituted 2-nitrophenols are important components of "brown carbon" from
      biomass burning. Photolysis is their major gas-phase degradation pathway. To
      determine the extent of light absorptions by 4-methyl-2-nitrophenol and 5-methyl
      2-nitrophenol, we obtained their absorption cross sections in the 295-400 nm
      region by using cavity ring-down spectroscopy. Cross-section values for 4-methyl
      2-nitrophenol were (1.01 +/- 0.07) * 10-18, (5.72 +/- 0.39) * 10-18, and (1.80 +/
      0.17) * 10-20 cm2/molecule at 295, 345, and 400 nm, where errors quoted
      represent 1sigma measurement uncertainty. Cross-section values for 5-methyl-2
      nitrophenol were (9.04 +/- 0.77) * 10-19, (5.89 +/- 0.54) * 10-18, and (2.81 +/-
      0.14) * 10-20 cm2/molecule at 295, 345, and 400 nm. The HONO, NO2, and OH
      formation channels following 308 and 351 nm photolysis of methyl-2-nitrophenols
      were investigated. The OH quantum yields at 308 and 351 nm were obtained as the
      ratio of the OH concentration generated in pump/probe laser overlap region to the
      photon density absorbed by methyl-substituted 2-nitrophenol in the same region;
      they were 0.066 +/- 0.021 and 0.031 +/- 0.017 for 4-methyl-2-nitrophenol and
      0.078 +/- 0.038 and 0.042 +/- 0.015 for 5-methyl-2-nitrophenol, where
      uncertainties represent 1sigma precision. The average HONO quantum yields at 308
      and 351 nm were 0.26 +/- 0.06 and 0.26 +/- 0.03 for 4-methyl-2-nitrophenol and
      0.37 +/- 0.05 and 0.35 +/- 0.06 for 5-methyl-2-nitrophenol. Estimated OH
      production rates from photolyzing 10 pptv of 4-methyl- and 5-methyl-2-nitrophenol
      are 2.3 * 106 and 3.0 * 106 molecules.cm-3.s-1 at 16.9 degrees  zenith angle.

PMID- 29376360
TI  - Steering the Geometry of Butterfly-Shaped Dimetal Carbide Cluster within a Carbon
      Cage via Trifluoromethylation of Y2C2@C82(6).
AB  - As one of the largest sub-branches of endohedral clusterfullerenes, dimetal
      carbide clusterfullerene (CCF) in the form of M2C2@C2 n is quite intriguing since
      an alternative structure of M2@C2 n+2 as conventional dimetallofullerene may
      exist as well. Herein, by using high-temperature trifluoromethylation followed by
      HPLC separation and single-crystal X-ray diffraction study, we report for the
      first time the unambiguous structural determination of yttrium (Y)-based CCF as
      its trifluoromethyl derivatives, Y2C2@C82(6)(CF3)16. Four isomers of
      Y2C2@C82(6)(CF3)16 with different addition patterns of 16 CF3 groups are
      successfully isolated, and two Y atoms of the butterfly-shaped Y2C2 cluster are
      coordinated by two cage pentagons in each isomer. The butterfly geometry of Y2C2
      cluster varies significantly in the four Y2C2@C82(6)(CF3)16 isomers, with Y...Y
      distances ranging from 3.544 to 4.051 A dependent on the relative positions of
      the two yttrium-coordinated pentagons on the carbon cage.

PMID- 29376361
TI  - Born-Oppenheimer Molecular Dynamics Simulations of a Bromate Ion in Water Reveal
      Its Dual Kosmotropic and Chaotropic Behavior.
AB  - The solvation structure and dynamics of a bromate (BrO3-) ion in water are
      studied by means of Born-Oppenheimer molecular dynamics simulations at two
      different temperatures using the Becke-Lee-Yang-Parr functional with Grimme D3
      dispersion corrections. The bromate ion possesses a pyramidal structure, and it
      has two types of solvation sites, namely, the bromine and oxygen atoms. We have
      looked at different radial and orientational distributions of water molecules
      around the bromate ion and also investigated their hydrogen bonding properties.
      The solvation structure of the bromate ion is also compared with that of the
      iodate (IO3-) ion, which is structurally rather similar to the bromate ion and
      was found to have some unusual solvation properties in water. It is found that
      the bromate ion follows a similar trend as that followed by the iodate ion as far
      as the solvation structure is concerned. However, the effect of the former on
      surrounding water is found to be much weaker than that of the latter. On the
      dynamical side, we have looked at diffusion, residence dynamics, and also the
      orientational and hydrogen bond relaxation of water molecules around the BrO3-
      ion and compared them with those of the bulk. Dynamical results are presented for
      both H2O and D2O around the BrO3- ion. Interpretation of the dynamical results in
      terms of structure-making (kosmotropic)/-breaking (chaotropic) properties of the
      BrO3- ion reveals that the bromine atom of this ion acts as a water structure
      breaker, whereas the three oxygens act as water structure makers. Thus, in spite
      of being a single ion, the bromate ion has dual characteristics and the
      experimentally observed kosmotropic ability of this ion is actually a trade-off
      between a chaotropic site (the bromine atom) and three kosmotropic sites (three
      oxygen atoms) that are present in the ion.

PMID- 29376362
TI  - Facile Dehydrogenation of Ethane on the IrO2(110) Surface.
AB  - Realizing the efficient and selective conversion of ethane to ethylene is
      important for improving the utilization of hydrocarbon resources, yet remains a
      major challenge in catalysis. Herein, ethane dehydrogenation on the IrO2(110)
      surface is investigated using temperature-programmed reaction spectroscopy (TPRS)
      and density functional theory (DFT) calculations. The results show that ethane
      forms strongly bound sigma-complexes on IrO2(110) and that a large fraction of
      the complexes undergo C-H bond cleavage during TPRS at temperatures below 200 K.
      Continued heating causes as much as 40% of the dissociated ethane to
      dehydrogenate and desorb as ethylene near 350 K, with the remainder oxidizing to
      COx species. Both TPRS and DFT show that ethylene desorption is the rate
      controlling step in the conversion of ethane to ethylene on IrO2(110) during
      TPRS. Partial hydrogenation of the IrO2(110) surface is found to enhance ethylene
      production from ethane while suppressing oxidation to COx species. DFT predicts
      that hydrogenation of reactive oxygen atoms of the IrO2(110) surface effectively
      deactivates these sites as H atom acceptors, and causes ethylene desorption to
      become favored over further dehydrogenation and oxidation of ethane-derived
      species. The study reveals that IrO2(110) exhibits an exceptional ability to
      promote ethane dehydrogenation to ethylene near room temperature, and provides
      molecular-level insights for understanding how surface properties influence
      selectivity toward ethylene production.

PMID- 29376363
TI  - Odor-Active Compounds in the Special Flavor Hops Huell Melon and Polaris.
AB  - The volatiles isolated from samples of the special flavor hop varieties, Huell
      Melon and Polaris, and from the aroma hop variety, Hallertau Tradition, by
      solvent extraction and solvent-assisted flavor evaporation (SAFE) were subjected
      to a comparative aroma extract dilution analysis (cAEDA), which resulted in 46
      odor-active compounds in the flavor dilution (FD) factor range of 16 to 2048. On
      the basis of high FD factors, myrcene, (3R)-linalool, and 2- and 3-methylbutanoic
      acid were confirmed as important variety-independent hop odorants. (1R,4S)
      Calamenene was identified for the first time as an odor-active compound in hops.
      Clear differences in the FD factors and their subsequent objectification by
      stable isotope dilution quantitation suggested that high concentrations of the
      esters ethyl 2-methylbutanoate, ethyl 2-methylpropanoate, and propyl 2
      methylbutanoate cause the characteristic fruity, cantaloupe-like odor note in
      Huell Melon hops, whereas the fruity and minty odor notes in Polaris are
      associated with high amounts of 3-methylbutyl acetate and 1,8-cineole.

PMID- 29376364
TI  - Linear and Nonlinear Optical Properties of Triphenylamine-Indandione
      Chromophores: Theoretical Study of the Structure-Function Relationship under the
      Combined Action of Substituent and Symmetry Change.
AB  - Linear and nonlinear optical properties of experimentally synthesized
      triphenylamine-indandione chromophores were investigated by time-dependent
      density functional theory calculations. The absorption and emission spectra, as
      well as the static and dynamic first hyperpolarizabilities related to the
      combined effect of substituent introduction and symmetry breaking, were discussed
      in detail. Theoretical analysis indicated the uniting of indandione acceptor
      group(s) with a precursor (triphenylamine, TriPhA), with the molecular symmetry
      destroyed simultaneously, leads to an obvious change in both the peak position
      and intensity of the linear spectra. The same process can also substantially
      magnify the molecular first hyperpolarizabilities. The triphenylamine-indandione
      molecules exhibit efficiencies in static first hyperpolarizability relative to
      that of the electron-donating TriPhA component and the electron-accepting
      indandione moiety. The optical nonlinearity would be further expanded under the
      influence of a resonance effect induced by appropriate excitation. Incident light
      with a wavelength nearly two times the one-photon absorption is likely to cause a
      greater frequency dispersion response. In particular, the first
      hyperpolarizabilities of the title compounds can be enlarged by about 3.2 times
      on average by resonance enhancement at a fundamental wavelength of 1064 nm.

PMID- 29376365
TI  - Mechanistic Unveiling of C?C Double-Bond Rotation and Origins of Regioselectivity
      and Product E/Z Selectivity of Pd-Catalyzed Olefinic C-H Functionalization of (E)
      N-Methoxy Cinnamamide.
AB  - Density functional theory (DFT) calculations have been performed to study the Pd
      catalyzed C-H functionalization of (E)-N-methoxy cinnamamide (E1), which
      selectively provides the alpha-C-H activation products (EP as minor product and
      its C?C rotation isomer ZP' as major product). Three crucial issues are solved:
      (i) The detailed mechanism leading to ZP' is one issue. The computational
      analyses of the mechanisms proposed in previously experimental and theoretical
      literature do not seem to be consistent with the experimental findings due to the
      high barriers involved. Alternatively, we present a novel oxidation/reduction
      promoted mechanism featuring the Pd(0) -> Pd(II) -> Pd(0) transformation. The
      newly proposed mechanism involves the initial coordination of the active catalyst
      PdL2 (L = t-BuCN) with the C?C bond in EP, followed by the oxidative
      cyclization/reductive decyclization-assisted C?C double-bond rotation processes
      resulting in ZP' and regeneration of PdL2. (ii) The origin of the product E/Z
      selectivity is the second issue. On the basis of the calculated results, it is
      found that, at the initial stage of the reaction, EP is certainly completely
      generated, while no ZP' formation occurred. Once E1 is used up, EP immediately
      acts as the partner of the new catalytic cycle and sluggishly evolves into ZP'. A
      small amount of generated ZP' would reversibly transform to EP due to the higher
      barrier involved. (iii) The intrinsic reasons for the regioselectivity are the
      third issue. The calculated results indicate that the regioselectivity for alpha
      C-H activation is mainly attributed to the stronger electrostatic attraction
      between the alpha-C and the metal center.

PMID- 29376368
TI  - Topology-Based Approach to Predict Relative Stabilities of Charged and
      Functionalized Fullerenes.
AB  - Understanding the relationship between structure and stability is one of the
      fundamental aspects of fullerene chemistry, as the number of possible cage
      isomers is very large and complexity increases by orders of magnitude when
      chemical groups are attached to the fullerene cage. The well-established
      stability rules valid for neutral fullerenes do not apply to many charged or
      functionalized fullerenes. Here we present the theory, implementation, and
      applications of two simple topology-based models that allow one to predict the
      relative stability of charged and functionalized fullerenes without the need for
      quantum chemistry calculations: (i) the charge stabilization index (CSI) model,
      based on the concepts of cage connectivity and frontier pi orbitals, which offers
      a general framework for the relative stability of both positively and negatively
      charged fullerenes, as well as endohedral metallofullerenes, and (ii) the
      exohedral fullerene stabilization index (XSI) model, which incorporates all key
      factors governing the stability of exohedral fullerenes, namely, pi
      delocalization, sigma strain, and steric hindrance between addends. Based
      exclusively on topological information, both models are powerful prescreening
      tools for predicting the most stable structures of a large number of charged and
      functionalized fullerenes. For easy use by fullerene chemists, both models have
      been implemented in the FullFun (for Fullerene Functionalization) software
      package, whose effectiveness and efficiency are demonstrated by some illustrative
      examples.

PMID- 29376366
TI  - A Regio- and Enantioselective CuH-Catalyzed Ketone Allylation with Terminal
      Allenes.
AB  - We report a method for the highly enantioselective CuH-catalyzed allylation of
      ketones that employs terminal allenes as allylmetal surrogates. Ketones and
      allenes bearing diverse and sensitive functional groups are efficiently coupled
      with high stereoselectivity and exclusive branched regioselectivity. In
      stoichiometric experiments, each elementary step of the proposed hydrocupration
      addition-metathesis mechanism can be followed by NMR spectroscopy.

PMID- 29376369
TI  - Deterministic Construction of Nodal Surfaces within Quantum Monte Carlo: The Case
      of FeS.
AB  - In diffusion Monte Carlo (DMC) methods, the nodes (or zeroes) of the trial wave
      function dictate the magnitude of the fixed-node (FN) error. In standard DMC
      implementations, the nodes are optimized by stochastically optimizing a short
      multideterminant expansion in the presence of an explicitly correlated Jastrow
      factor. Here, following a recent proposal, we pursue a different route and
      consider the nodes of selected configuration interaction (sCI) expansions built
      with the CIPSI (Configuration Interaction using a Perturbative Selection made
      Iteratively) algorithm. By increasing the size of the sCI expansion, these nodes
      can be systematically and deterministically improved. The present methodology is
      used to investigate the properties of the transition metal sulfide molecule FeS.
      This apparently simple molecule has been shown to be particularly challenging for
      electronic structure theory methods due to the proximity of two low-energy
      quintet electronic states of different spatial symmetry and the difficulty to
      treat them on equal footing from a one-electron basis set point of view. In
      particular, we show that, at the triple-zeta basis set level, all sCI results
      including those extrapolated at the full CI (FCI) limit-disagree with experiment,
      yielding an electronic ground state of 5Sigma+ symmetry. Performing FN-DMC
      simulation with sCI nodes, we show that the correct 5Delta ground state is
      obtained if sufficiently large expansions are used. Moreover, we show that one
      can systematically get accurate potential energy surfaces and reproduce the
      experimental dissociation energy as well as other spectroscopic constants.

PMID- 29376367
TI  - Potent and Selective Inhibitors of 8-Oxoguanine DNA Glycosylase.
AB  - The activity of DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1), which
      excises oxidized base 8-oxoguanine (8-OG) from DNA, is closely linked to
      mutagenesis, genotoxicity, cancer, and inflammation. To test the roles of OGG1
      mediated repair in these pathways, we have undertaken the development of
      noncovalent small-molecule inhibitors of the enzyme. Screening of a PubChem
      annotated library using a recently developed fluorogenic 8-OG excision assay
      resulted in multiple validated hit structures, including selected lead hit
      tetrahydroquinoline 1 (IC50 = 1.7 MUM). Optimization of the tetrahydroquinoline
      scaffold over five regions of the structure ultimately yielded amidobiphenyl
      compound 41 (SU0268; IC50 = 0.059 MUM). SU0268 was confirmed by surface plasmon
      resonance studies to bind the enzyme both in the absence and in the presence of
      DNA. The compound SU0268 was shown to be selective for inhibiting OGG1 over
      multiple repair enzymes, including other base excision repair enzymes, and
      displayed no toxicity in two human cell lines at 10 MUM. Finally, experiments
      confirm the ability of SU0268 to inhibit OGG1 in HeLa cells, resulting in an
      increase in accumulation of 8-OG in DNA. The results suggest the compound SU0268
      as a potentially useful tool in studies of the role of OGG1 in multiple disease
      related pathways.

PMID- 29376370
TI  - Developmental Toxicity of the Organic Fraction from Hydraulic Fracturing Flowback
      and Produced Waters to Early Life Stages of Zebrafish ( Danio rerio).
AB  - Hydraulic fracturing (HF) has emerged as a major recovery method of
      unconventional oil and gas reservoirs and concerns have been raised regarding the
      environmental impact of releases of Flowback and Produced Water (FPW) to aquatic
      ecosystems. To investigate potential effects of HF-FPW on fish embryo
      development, HF-FPW samples were collected from two different wells and the
      organic fractions were isolated from both aqueous and particle phases to
      eliminate the confounding effects of high salinity. Each organic extract was
      characterized by non-target analysis with HPLC-Orbitrap-MS, with targeted
      analysis for polycyclic aromatic hydrocarbons provided as markers of petroleum
      affected water. The organic profiles differed between samples, including PAHs and
      alkyl PAHs, and major substances identified by non-target analysis included
      polyethylene glycols, alkyl ethoxylates, octylphenol ethoxylates, and other high
      molecular weight (C49-79) ethylene oxide polymeric material. Zebrafish embryos
      were exposed to various concentrations of FPW organic extracts to investigate
      acute (7-day) and developmental toxicity in early life stages. The acute toxicity
      (LD50) of the extracted FPW fractions ranged from 2.8* to 26* the original
      organic content. Each extracted FPW fraction significantly increased spinal
      malformation, pericardial edema, and delayed hatch in exposed embryos and altered
      the expression of a suite of target genes related to biotransformation, oxidative
      stress, and endocrine-mediation in developing zebrafish embryos. These results
      provide novel information on the variation of organic profiles and developmental
      toxicity among different sources and fractions of HF-FPWs.

PMID- 29376371
TI  - High-Performance Magnetorheological Suspensions of Pickering-Emulsion-Polymerized
      Polystyrene/Fe3O4 Particles with Enhanced Stability.
AB  - The magnetorheological (MR) performance of suspensions based on core-shell
      structured foamed polystyrene (PSF)/Fe3O4 particles was investigated by using a
      vibrating sample magnetometer and a rotational rheometer. Core-shell-structured
      polystyrene (PS)/Fe3O4 was synthesized by using the Pickering-emulsion
      polymerization method in which Fe3O4 nanoparticles were added as a solid
      surfactant. Foaming the PS core in PS/Fe3O4 particles was carried out by using a
      supercritical carbon dioxide (scCO2) fluid. The density was measured by a
      pycnometer. The densities of PS/Fe3O4 and PSF/Fe3O4 particles were significantly
      lowered from that of the pure Fe3O4 particle after Pickering-emulsion
      polymerization and foaming treatment. All tested suspensions displayed similar MR
      behaviors but different yield strengths. The important parameter that determined
      the MR performance was not the particle density but rather the surface density of
      Fe3O4 on the PS core surface. The morphology was observed by scanning electron
      microscopy and transmission electron microscopy. Most Fe3O4 particles stayed on
      the surface of PS/Fe3O4 particles, making the surface topology bumpy and rough,
      which decreased the particle sedimentation velocity. Finally, Turbiscan apparatus
      was used to examine the sedimentation properties of different particle
      suspensions. The suspensions of PS/Fe3O4 and PSF/Fe3O4 showed remarkably improved
      stability against sedimentation, much better than the bare Fe3O4 particle
      suspension because of the reduced density mismatch between the nanoparticles and
      the carrier medium as well as the surface topology change.

PMID- 29376372
TI  - Selectivity and Mechanism of Fengycin, an Antimicrobial Lipopeptide, from
      Molecular Dynamics.
AB  - Fengycin is a cyclic lipopeptide used as an agricultural fungicide. It is
      synthesized by Bacillus subtilis as an immune response against fungal infection
      and functions by damaging the target's cell membrane. Previous molecular dynamics
      simulations and experiments have led to the hypothesis that the aggregation of
      fengycins on the membrane surface plays a key role in cell disruption. Here, we
      used microsecond-scale all-atom molecular dynamics simulations to understand the
      specificity, selectivity, and structure of fengycin oligomers. Our simulations
      suggest that fengycin is more likely to form stable oligomers in model fungal
      membranes (phosphatidylcholine) compared to the model bacterial membranes
      (phosphatidylethanolamine:phosphatidylglycerol). Furthermore, we characterize the
      differences in the structure and kinetics of the membrane-bound aggregates and
      discuss their functional implications.

PMID- 29376373
TI  - Thermally Absorptive Blankets for Highly Efficient Snowbank Melting.
AB  - Fallen snow is one of the most reflective surfaces found in nature. As a result,
      snowbanks can take many weeks to melt even when the air temperature is above
      freezing. Here, we introduce a simple and passive method for quickly melting
      snowbanks by draping a thermally absorptive blanket over the snow. Using
      controlled experimental conditions, it was observed that snowbanks can melt 300%
      faster when a thermally absorptive blanket is placed on top. The mechanism is the
      threefold increase in absorptivity of the spray-coated blanket compared to bare
      snow, which allows the vast majority of the irradiation to be used to overcome
      the latent heat of fusion.

PMID- 29376374
TI  - Selective Coherent Anti-Stokes Raman Scattering Microscopy Employing Dual
      Wavelength Nanofocused Ultrafast Plasmon Pulses.
AB  - Ultrafast surface plasmon polariton (SPP) nanofocusing on a plasmonic metal
      tapered tip with femtosecond laser pulses enables background-free localized
      excitation beyond the diffraction limit. We demonstrate simultaneous nanofocusing
      of ultrafast SPP pulses at 440 and 800 nm, which were coupled with a common
      diffraction grating structure fabricated on an aluminum (Al) tapered tip, to the
      tip apex with a radius of ~35 nm. We achieved selective coherent anti-Stokes
      Raman scattering (CARS) microscopy that combined an 800 nm (omega) SPP pump
      pulse, which achieves selective vibrational excitation by spectral focusing, and
      a 440 nm (2omega) SPP probe pulse. Raman intensity of this novel 2omega-CARS
      increased by a factor of 3.96 at the G-band and 4.00 at the 2D-band compared with
      that with omega-CARS for the monolayer graphene. The 2omega-CARS imaging method
      was applied for imaging a multiwalled carbon nanotube at the D-, G-, and 2D
      bands. This dual-wavelength nanofocusing will open up new nanoscale
      microspectroscopy and optical excitation at the tip apex, such as sum frequency
      mixing, two-photon excitation.

PMID- 29376375
TI  - Probing Charge Transport through Peptide Bonds.
AB  - We measure the conductance of unmodified peptides at the single-molecule level
      using the scanning tunneling microscope-based break-junction method, utilizing
      the N-terminal amine group and the C-terminal carboxyl group as gold metal
      binding linkers. Our conductance measurements of oligoglycine and oligoalanine
      backbones do not rely on peptide side-chain linkers. We compare our results with
      alkanes terminated asymmetrically with an amine group on one end and a carboxyl
      group on the other to show that peptide bonds decrease the conductance of an
      otherwise saturated carbon chain. Using a newly developed first-principles
      approach, we attribute the decrease in conductance to charge localization at the
      peptide bond, which reduces the energy of the frontier orbitals relative to the
      Fermi energy and the electronic coupling to the leads, lowering the tunneling
      probability. Crucially, this manifests as an increase in conductance decay of
      peptide backbones with increasing length when compared with alkanes.

PMID- 29376376
TI  - Surface Chemistry Dependence of Mechanochemical Reaction of Adsorbed Molecules-An
      Experimental Study on Tribopolymerization of alpha-Pinene on Metal, Metal Oxide,
      and Carbon Surfaces.
AB  - Mechanochemical reactions between adsorbate molecules sheared at tribological
      interfaces can induce association of adsorbed molecules, forming oligomeric and
      polymeric products often called tribopolymers). This study revealed the role or
      effect of surface chemistry of the solid substrate in mechanochemical
      polymerization reactions. As a model reactant, alpha-pinene was chosen because it
      was known to readily form tribopolymers at the sliding interface of stainless
      steel under vapor-phase lubrication conditions. Eight different substrate
      materials were tested-palladium, nickel, copper, stainless steel, gold, silicon
      oxide, aluminum oxide, and diamond-like carbon (DLC). All metal substrates and
      DLC were initially covered with surface oxide species formed naturally in air or
      during the oxidative sample cleaning. It was found that the tribopolymerization
      yield of alpha-pinene is much higher on the substrates that can chemisorb alpha
      pinene, compared to the ones on which only physisorption occurs. From the load
      dependence of the tribopolymerization yield, it was found that the surfaces
      capable of chemisorption give a smaller critical activation volume for the
      mechanochemical reaction, compared to the ones capable of physisorption only. On
      the basis of these observations and infrared spectroscopy analyses of the
      adsorbed molecules and the produced polymers, it was concluded that the
      mechanochemical reaction mechanisms might be different between chemically
      reactive and inert surfaces and that the chemical reactivity of the substrate
      surface greatly influences the tribochemical polymerization reactions of adsorbed
      molecules.

PMID- 29376377
TI  - X-ray-Induced Fragmentation of Imidazolium-Based Ionic Liquids Studied by Soft X
      ray Absorption Spectroscopy.
AB  - We investigated the X-ray absorption spectroscopy (XAS) fingerprint of EMImTFSI
      ionic liquid (IL) and its fragmentation products created by X-ray irradiation. To
      accomplish this, we used an open geometry where an IL droplet is directly exposed
      in the vacuum chamber and an enclosed geometry where the IL is confined in a cell
      covered by an X-ray transparent membrane. In the open geometry, the XAS signature
      was stable and consistent with experimental and theoretical spectra reported in
      the literature. In contrast, when the IL is enclosed, its XAS evolves
      continuously under X-ray illumination due to the accumulation of volatile
      fragmentation products inside the closed cell, while they evaporate in the open
      geometry. The changes in the XAS from the core levels of relevant elements (C, N,
      S, F) together with density functional theory calculations allowed us to identify
      the chemical nature of the fragment products and the chemical bonds most
      vulnerable to rupture under soft X-ray irradiation.

PMID- 29376378
TI  - Colloidal Nanocrystals of Lead-Free Double-Perovskite (Elpasolite)
      Semiconductors: Synthesis and Anion Exchange To Access New Materials.
AB  - Concerns about the toxicity and instability of lead-halide perovskites have
      driven a recent surge in research toward alternative lead-free perovskite
      materials, including lead-free double perovskites with the elpasolite structure
      and visible bandgaps. Synthetic approaches to this class of materials remain
      limited, however, and no examples of heterometallic elpasolites as nanomaterials
      have been reported. Here, we report the synthesis and characterization of
      colloidal nanocrystals of Cs2AgBiX6 (X = Cl, Br) elpasolites using a hot
      injection approach. We further show that postsynthetic modification through anion
      exchange and cation extraction can be used to convert these nanocrystals to new
      materials including Cs2AgBiI6, which was previously unknown experimentally.
      Nanocrystals of Cs2AgBiI6, synthesized via a novel anion-exchange protocol using
      trimethylsilyl iodide, have strong absorption throughout the visible region,
      confirming theoretical predictions that this material could be a promising
      photovoltaic absorber. The synthetic methodologies presented here are expected to
      be broadly generalizable. This work demonstrates that nanocrystal ion-exchange
      reactivity can be used to discover and develop new lead-free halide perovskite
      materials that may be difficult or impossible to access through direct synthesis.

PMID- 29376379
TI  - Preparation and Structural Characterization of Free-Standing Octacalcium
      Phosphate-Rich Thin Films.
AB  - Free-standing films of calcium phosphates exhibit many favorable properties for
      tissue engineering. In this work, a thin film of calcium phosphate is prepared in
      a liposome suspension using the method of ammonia gas diffusion. The thickness of
      the film is about 10 MUm, and the lateral dimensions are on the length scale of
      millimeter. The results of powder X-ray diffraction and transmission electron
      microscopy show that the thin films contain the mineral phases of hydroxyapatite
      and octacalcium phosphate (OCP). Using solid-state NMR spectroscopy, in
      particular the technique of heteronuclear correlation spectroscopy with variable
      contact time, the major crystalline phase of the thin film has been confirmed to
      be OCP.

PMID- 29376380
TI  - Multimodal, pH Sensitive, and Magnetically Assisted Carrier of Doxorubicin
      Designed and Analyzed by Means of Computer Simulations.
AB  - This work deals with an analysis of drugs carriers based on the structure of a
      carbon nanotube using large-scale atomistic molecular dynamics simulations. The
      analyzed systems link several functions in a single architecture. They are as
      follows: (i) the sidewalls and tips of carbon nanotubes are covalently
      functionalized by polyethylene glycol-folic acid conjugates, and this approach
      allows for creation of hydrophytic and biocompatible systems; (ii) doxorubicin is
      kept in the internal space of a carbon nanotube as a mixture with dyes (p
      phenylenediamine or neutral red)-it allows for pH-controlled release or
      alteration of the interaction topology; (iii) the mixture of doxorubicin and dyes
      in the nanotube interior is additionally sealed by fullerene nanoparticles which
      act as pistons at acidic pH and loosen the tangle of polyethylene glycol chains
      at the nanotube tips. This enhances the release of doxorubicin from the nanotube
      when compared to the analogous system but without the fullerene caps; (iv)
      another function of the carrier can be activated by filling of the fullerenes by
      magnetic material-then, the carrier can be visualized by means of magnetic
      resonance imaging, it can realize magnetic hyperthermia of tumor cells, and
      intense rotation of the nanoparticles can be induced by the application of an
      external magnetic field. That rotation enhances the release of doxorubicin from
      the nanotube and leads to the increase of the rotational temperature. The studies
      show that the proposed design of the drug-doxorubicin carrier reveals very
      promising properties. Its fabrication is absolutely feasible, as all individual
      stages necessary for its construction have been confirmed in the literature.

PMID- 29376381
TI  - Plasmonic Hot Carriers-Controlled Second Harmonic Generation in WSe2 Bilayers.
AB  - Modulating second harmonic generation (SHG) by a static electric field through
      either electric-field-induced SHG or charge-induced SHG has been well documented.
      Nonetheless, it is essential to develop the ability to dynamically control and
      manipulate the nonlinear properties, preferably at high speed. Plasmonic hot
      carriers can be resonantly excited in metal nanoparticles and then injected into
      semiconductors within 10-100 fs, where they eventually decay on a comparable time
      scale. This allows one to rapidly manipulate all kinds of characteristics of
      semiconductors, including their nonlinear properties. Here we demonstrate that
      plasmonically generated hot electrons can be injected from plasmonic
      nanostructure into bilayer (2L) tungsten diselenide (WSe2), breaking the material
      inversion symmetry and thus inducing an SHG. With a set of pump-probe experiments
      we confirm that it is the dynamic separation electric field resulting from the
      hot carrier injection (rather than a simple optical field enhancement) that is
      the cause of SHG. Transient absorption measurement further substantiate the
      plasmonic hot electrons injection and allow us to measure a rise time of ~120 fs
      and a fall time of 1.9 ps. Our study creates opportunity for the ultrafast all
      optical control of SHG in an all-optical manner that may enable a variety of
      applications.

PMID- 29376382
TI  - Simple, Hackable, Size-Selective, Amine-Functionalized Fe-Oxide Nanoparticles for
      Biomedical Applications.
AB  - A facile one-pot method for synthesizing amine-functionalized nonspherical Fe3O4
      nanoparticles in gram-scale quantities is presented using just a single source of
      iron (iron(II) chloride) and an amine (triethylamine). The amine not only
      transforms iron salt to Fe3O4, but also directs the morphology of the
      nanoparticles along with the temperature of the reaction and functionalizes them,
      making the synthesis very economical. By modifying the surface further, these
      nanoparticles promise to offer useful biomedical applications. For example, after
      biocide coating, the particles are found to be 100% effective in deactivating
      methicillin-resistant Staphylococcus aureus (MRSA) bacteria in 2 h. Cellular
      uptake studies using biocompatible EDTA-Na3 (N-(trimethoxysilyl
      propyl)ethylenediaminetriacetate, trisodium salt)-coated nanoparticles in human
      glioblastoma U-251 cells show that the majority of the particles are internalized
      by the cells in the presence of a small dc-magnetic field, making these particles
      a potential candidate as drug carriers for magnetic field-targeted delivery and
      hyperthermia.

PMID- 29376383
TI  - Dynamic Photochemical and Optoelectronic Control of Photonic Fano Resonances via
      Monolayer MoS2 Trions.
AB  - Active tunability of photonic resonances is of great interest for various
      applications such as optical switching and modulation based on optoelectronic
      materials. Manipulation of charged excitons in atomically thin transition metal
      dichalcogenides (TMDCs) like monolayer MoS2 offers an unexplored route for
      diverse functionalities in optoelectronic nanodevices. Here, we experimentally
      demonstrate the dynamic photochemical and optoelectronic control of the photonic
      crystal Fano resonances by optical and electrical tuning of monolayer MoS2
      refractive index via trions without any chemical treatment. The strong spatial
      and spectral overlap between the photonic Fano mode and the active MoS2 monolayer
      enables efficient modulation of the Fano resonance. Our approach offers new
      directions for potential applications in the development of optical modulators
      based on emerging 2D direct band gap semiconductors.

PMID- 29376384
TI  - Effect of Reinforcement at Length Scale for Polyurethane Cellular Scaffolds by
      Supramolecular Assemblies.
AB  - This study is aimed to represent the role of carbonaceous nanofillers to
      reinforce the commercially available polyurethane porous structure. The effect of
      dimensionality of fillers to anchor the construction of stable three-dimensional
      (3D) cellular architectures has been highlighted. The cellular frameworks of
      commercially available thermoplastic polyurethane (TPU) have been fabricated
      through the thermoreversible supramolecular self-assembly route. It was
      established that the minimum shrinkage of TPU lattice structures occurred when
      the solid-state network is strengthened by the topologically engineered 3D
      hierarchical nanofillers, where the amount of reinforcement was found to play a
      critical role. It has been established by series of structure-property
      correlations that reinforcing the cellular structure to endure the capillary
      stress is equally effective as supercritical drying for producing low-density
      porous morphologies. The removal of liquid phase from gel is as important as the
      presence of 3D fillers in the matrix for reinforcing the cellular structures when
      replacing the solvent phase with air to generate a two-phase solid-gas engineered
      morphology. The insight into the polyurethane network structure revealed that the
      dimensionality, amount, and distribution of fillers in the matrix are critical
      for reinforcing the cellular scaffolds in solid gel without any cross-linking.

PMID- 29376385
TI  - Synthesis and Concentration of Organosols of Silver Nanoparticles Stabilized by
      AOT: Emulsion Versus Microemulsion.
AB  - In this work, we tried to combine the advantages of microemulsion and emulsion
      synthesis to obtain stable concentrated organosols of Ag nanoparticles, promising
      liquid-phase materials. Starting reagents were successively introduced into a
      micellar solution of sodium bis-(2-ethylhexyl)sulfosuccinate (AOT) in n-decane in
      the dynamic reverse emulsion mode. During the contact of the phases, Ag+ passes
      into micelles and Na+ passes into emulsion microdroplets through the cation
      exchange AOTNaOrg + AgNO3Aq = AOTAgOrg + NaNO3Aq. High concentrations of NaNO3
      and hydrazine in the microdroplets favor an osmotic outflow of water from the
      micelles, which reduces their polar cavities to ~2 nm. As a result, silver ions
      are contained in the micelles, and the reducing agent is present mostly in
      emulsion microdroplets. The reagents interact in the polar cavities of micelles
      to form ~7 nm Ag nanoparticles. The produced nanoparticles are positively
      charged, which permitted their electrophoretic concentration to obtain liquid
      concentrates (up to 30% Ag) and a solid Ag-AOT composite (up to 75% Ag). Their
      treatment at 250  degrees C leads to the formation of conductive films (180 mOhm
      per square). The developed technique makes it possible to increase the
      productivity of the process by ~30 times and opens up new avenues of practical
      application for the well-studied microemulsion synthesis.

PMID- 29376386
TI  - Gold Raspberry-Like Colloidosomes Prepared at the Water-Nitromethane Interface.
AB  - In this study, we propose a simple shake-flask method to produce micron-size
      colloidosomes from a liquid-liquid interface functionalized with a gold
      nanoparticle (AuNP) film. A step-by-step extraction process of an organic phase
      partially miscible with water led to the formation of raspberry-like structures
      covered and protected by a gold nanofilm. The distinctive feature of the prepared
      colloidosomes is a very thin shell consisting of small AuNPs of 12 or 38 nm in
      diameter instead of several hundred nanometers reported previously. The
      interesting and remarkable property of the proposed approach is their
      reversibility: the colloidosomes may be easily transformed back to a nanofilm
      state simply by adding pure organic solvent. The obtained colloidosomes have a
      broadband absorbance spectrum, which makes them of great interest in applications
      such as photothermal therapy, surface-enhanced Raman spectroscopy studies, and
      microreactor vesicles for interfacial electrocatalysis.

PMID- 29376387
TI  - Construction of a Hierarchical Architecture of Covalent Organic Frameworks via a
      Postsynthetic Approach.
AB  - Covalent organic frameworks (COFs) represent an emerging class of crystalline
      porous materials that are constructed by the assembly of organic building blocks
      linked via covalent bonds. Several strategies have been developed for the
      construction of new COF structures; however, a facile approach to fabricate
      hierarchical COF architectures with controlled domain structures remains a
      significant challenge, and has not yet been achieved. In this study, a dynamic
      covalent chemistry (DCC)-based postsynthetic approach was employed at the solid
      liquid interface to construct such structures. Two-dimensional imine-bonded COFs
      having different aromatic groups were prepared, and a homogeneously mixed-linker
      structure and a heterogeneously core-shell hollow structure were fabricated by
      controlling the reactivity of the postsynthetic reactions. Solid-state nuclear
      magnetic resonance (NMR) spectroscopy and transmission electron microscopy (TEM)
      confirmed the structures. COFs prepared by a postsynthetic approach exhibit
      several functional advantages compared with their parent phases. Their Brunauer
      Emmett-Teller (BET) surface areas are 2-fold greater than those of their parent
      phases because of the higher crystallinity. In addition, the hydrophilicity of
      the material and the stepwise adsorption isotherms of H2O vapor in the
      hierarchical frameworks were precisely controlled, which was feasible because of
      the distribution of various domains of the two COFs by controlling the
      postsynthetic reaction. The approach opens new routes for constructing COF
      architectures with functionalities that are not possible in a single phase.

PMID- 29376388
TI  - U2@ I h(7)-C80: Crystallographic Characterization of a Long-Sought Dimetallic
      Actinide Endohedral Fullerene.
AB  - The nature of actinide-actinide bonds has attracted considerable attention for a
      long time, especially since recent theoretical studies suggest that triple and up
      to quintuple bonds should be possible, but little is known experimentally.
      Actinide-actinide bonds inside fullerene cages have also been proposed, but their
      existence has been debated intensively by theoreticians. Despite all the
      theoretical arguments, critical experimental data for a dimetallic actinide
      endohedral fullerene have never been obtained. Herein, we report the synthesis
      and isolation of a dimetallic actinide endohedral metallofullerene (EMF), U2@C80.
      This compound was fully characterized by mass spectrometry, single crystal X-ray
      crystallography, UV-vis-NIR spectroscopy, Raman spectroscopy, cyclic voltammetry,
      and X-ray absorption spectroscopy (XAS). The single crystal X-ray
      crystallographic analysis unambiguously assigned the molecular structure to U2@ I
      h(7)-C80. In particular, the crystallographic data revealed that the U-U distance
      is within the range of 3.46-3.79 A, which is shorter than the 3.9 A previously
      predicted for an elongated weak U-U bond inside the C80 cage. The XAS results
      reveal that the formal charge of the U atoms trapped inside the fullerene cage is
      +3, which agrees with the computational and crystallographic studies that assign
      a hexaanionic carbon cage, ( I h-C80)6-. Theoretical studies confirm the presence
      of a U-U bonding interaction and suggest that the weak U-U bond in U2@ I h(7)-C80
      is strengthened upon reduction and weakened upon oxidation. The comprehensive
      characterization of U2@ I h(7)-C80 and the overall agreement between the
      experimental data and theoretical investigations provide experimental proof and
      deeper understanding for actinide metal-metal bonding interactions inside a
      fullerene cage.

PMID- 29376389
TI  - Noncollinear Two-Component Quasirelativistic Description of Spin Interactions in
      Exchange-Coupled Systems. Mapping Generalized Broken-Symmetry States to Effective
      Spin Hamiltonians.
AB  - We provide a consistent mapping of noncollinear two-component quasirelativistic
      DFT energies with appropriate orientations of localized spinor quantization axes
      for multinuclear exchange-coupled transition-metal complexes onto an uncoupled
      anisotropic effective spin Hamiltonian. This provides access to the full exchange
      interaction tensor between the centers of spin-coupled systems in a consistent
      way. The proposed methodology may be best viewed as a generalized broken-symmetry
      density functional theory approach (gBS-DFT). While the calculations provided are
      limited to trinuclear systems ([M3O(OOCH)6(H2O)3]+, where M = Cr(III), Mn(III),
      Fe(III)) with C3 symmetry, the method provides a general framework that is
      extendable to arbitrary systems. It offers an alternative to previous approaches
      to single-ion zero-field splittings, and it provides access to the less often
      examined antisymmetric Dzyaloshinskii-Moriya exchange interaction. Spin-orbit
      coupling is included self-consistently. This will be of particular importance for
      complexes involving 4d or 5d transition metal centers or possibly also for f
      block elements, where a perturbational treatment of spin-orbit coupling may not
      be valid anymore. While a comparison with experimental data was indirect due to
      simplifications in the chosen model structures, the agreement obtained indicates
      the essential soundness of the presented approach.

PMID- 29376393
TI  - Correction.

PMID- 29376390
TI  - Guided Heterogeneous Nucleation of Sodium Chloride at Self-Assembled Monolayer
      Modified Nanoporous Gold Films.
AB  - Drug delivery devices are generally inefficient when releasing the active
      compound at the targeted position. In this work, we investigate nanoporous gold
      (np-Au) as the drug eluting device, and we use the precipitation of NaCl as a
      model of drug sedimentation to evaluate the patterns of solute distribution.
      Hydrophilic and hydrophobic modifications of np-Au result in different, but both
      inhomogeneous, release patterns, with most of the precipitate forming outside the
      device. In contrast, the fabrication of a hydrophobic-hydrophilic-layered
      architecture allows full penetration through the bicontinuous np-Au network,
      resulting in a homogeneous release pattern. Similar architectures could be used
      to enhance the efficacy of drug delivery.

PMID- 29376398
TI  - Spontaneous coronary artery dissection: Acute findings on coronary computed
      tomography angiography.
AB  - BACKGROUND: The coronary computed tomography angiography features of acute
      spontaneous coronary artery dissection, an important cause of acute coronary
      syndrome in young women, have not been assessed. METHODS: The "Virtual"
      Multicenter Mayo Clinic Spontaneous Coronary Artery Dissection Registry was
      established in 2010 and includes retrospective and prospective patient data.
      Retrospective assessment of acute coronary computed tomography angiography images
      was performed for 14 patients (16 vessels) who had images performed within two
      days of invasive coronary angiography diagnosis of acute spontaneous coronary
      artery dissection. RESULTS: Four pertinent diagnostic coronary features of acute
      spontaneous coronary artery dissection were observed in order of prevalence: 1)
      abrupt luminal stenosis (64%); 2) intramural hematoma (50%); 3) tapered luminal
      stenosis (36%); and 4) dissection (14%). Additional findings include epicardial
      fat stranding (42%), coronary tortuosity (29%), and coronary bridge (14%). Fifty
      percent of patients had myocardial hypoperfusion in the myocardial distribution
      of the dissected coronary artery. CONCLUSIONS: We define key coronary computed
      tomography angiography features of acute spontaneous coronary artery dissection,
      the most common of which are abrupt luminal stenosis and intramural hematoma.
      Importantly, intramural hematoma appears similar to noncalcified atherosclerotic
      plaque, emphasizing the importance of invasive coronary angiography for acute
      diagnosis of spontaneous coronary artery dissection until the sensitivity and
      specificity of coronary computed tomography angiography is better understood.

PMID- 29376397
TI  - Associations between parental broader autism phenotype and child autism spectrum
      disorder phenotype in the Study to Explore Early Development.
AB  - The autism spectrum disorder phenotype varies by social and communication ability
      and co-occurring developmental, behavioral, and medical conditions. Etiology is
      also diverse, with myriad potential genetic origins and environmental risk
      factors. Examining the influence of parental broader autism phenotype-a set of
      sub-clinical characteristics of autism spectrum disorder-on child autism spectrum
      disorder phenotypes may help reduce heterogeneity in potential genetic
      predisposition for autism spectrum disorder. We assessed the associations between
      parental broader autism phenotype and child phenotype among children of age 30-68
      months enrolled in the Study to Explore Early Development (N = 707). Child autism
      spectrum disorder phenotype was defined by a replication of latent classes
      derived from multiple developmental and behavioral measures: Mild Language Delay
      with Cognitive Rigidity, Mild Language and Motor Delay with Dysregulation (e.g.
      anxiety/depression), General Developmental Delay, and Significant Developmental
      Delay with Repetitive Motor Behaviors. Scores on the Social Responsiveness Scale
      Adult measured parent broader autism phenotype. Broader autism phenotype in at
      least one parent was associated with a child having increased odds of being
      classified as mild language and motor delay with dysregulation compared to
      significant developmental delay with repetitive motor behaviors (odds ratio:
      2.44; 95% confidence interval: 1.16, 5.09). Children of parents with broader
      autism phenotype were more likely to have a phenotype qualitatively similar to
      broader autism phenotype presentation; this may have implications for etiologic
      research.

PMID- 29376399
TI  - Effects of chronic beta-blocker treatment on admission haemodynamics in STEMI
      patients treated with primary angioplasty.
AB  - BACKGROUND: The association between chronic beta-blocker treatment and
      haemodynamics at admission in patients with ST-segment elevation myocardial
      infarction treated by primary percutaneous coronary intervention is not well
      studied. We investigated the impact of chronic beta-blocker treatment on the risk
      of cardiogenic shock and pre-shock at admission in patients with ST-segment
      elevation myocardial infarction treated by primary percutaneous coronary
      intervention. METHODS AND RESULTS: A total of 4907 patients with ST-segment
      elevation myocardial infarction treated with primary percutaneous coronary
      intervention were included in the study. A total of 1148 patients (23.3%) were on
      chronic beta-blocker treatment. Cardiogenic shock was observed in 264 patients
      (5.3%). Pre-shock was defined as a shock index (the ratio of heart rate and
      systolic blood pressure) of 0.7 or greater, and was observed in 1022 patients
      (20.8%). The risk of cardiogenic shock in patients with chronic beta-blocker
      treatment was not increased (adjusted hazard ratio (HR) 0.97, 95% confidence
      interval (CI) 0.65-1.46, P=0.90). Chronic beta-blocker treatment was also not
      associated with an increased risk of pre-shock (adjusted HR 0.86, 95% CI 0.68
      1.07, P=0.19). Also after propensity score matched analysis, there was no
      increased risk of cardiogenic shock or pre-shock in patients with chronic beta
      blocker treatment (respectively HR 0.97, 95% CI 0.61-1.51, P=0.88 and HR 0.82,
      95% CI 0.65-1.06, P=0.12). CONCLUSION: In ST-segment elevation myocardial
      infarction, chronic beta-blocker treatment is not associated with an increased
      risk of cardiogenic shock or pre-shock.

PMID- 29376401
TI  - Polybrominated diphenyl ethers (PBDEs) levels in blood samples from children
      living in the metropolitan area of Guadalajara, Jalisco, Mexico.
AB  - The aim of this study was to perform a polybrominated diphenyl ethers (PBDEs)
      exposure assessment using blood samples collected from children living in the
      metropolitan area of Guadalajara, Jalisco, Mexico (GDL). Five congeners of PBDEs
      were analyzed using a gas chromatography/mass spectrometry technique. The blood
      concentrations of total PBDEs ranged from 5.50 to 169 ng/g lipid (42.0 +/- 18.0
      ng/g lipid; mean +/- standard deviation). Regarding BDE congeners, the main
      congener (highest blood levels) was BDE99 (14.5 +/- 5.50 ng/g lipid), followed by
      BDE100 (9.80 +/- 3.40 ng/g lipid) and BDE154 (9.80 +/- 5.90 ng/g lipid), and
      finally BDE153 (5.80 +/- 2.30 ng/g lipid) and BDE47 (2.20 +/- 1.20 ng/g lipid).
      In conclusion, blood PBDEs concentrations of concern were detected in this study,
      as blood levels were similar to the ones found in North America (the highest
      worldwide).

PMID- 29376400
TI  - Global named patient use program of afatinib in advanced non-small-cell lung
      carcinoma patients who progressed following prior therapies.
AB  - AIM: A global afatinib named patient use program in non-small-cell lung carcinoma
      (NSCLC) commenced in 2010. MATERIALS & METHODS: Eligible NSCLC patients had
      progressed after clinical benefit on prior erlotinib/gefitinib and/or had
      activating EGFR/HER2 mutations, exhausted all other treatments, and were
      ineligible for afatinib trials. RESULTS: Data, as of January 2016, were reported
      on 3966 heavily pretreated NSCLC patients (41 countries; six continents). Among
      2595/3966 (65.4%) patients with tumor EGFR status, 2407 (92.8%) were EGFR
      mutation positive. Median time to treatment failure (2862/3966 [72.2%] patients
      with available data) was 4.4 months. Among 1141/2862 (39.9%) patients with
      response reported, objective response rate was 23.4% (267/1141). Safety findings
      were as expected. CONCLUSION: Time to treatment failure durations and objective
      response rates were encouraging.

PMID- 29376402
TI  - Cost assessment of treatment of acute myocardial infarction and angiographically
      visible coronary thrombus.
AB  - AIM: Study was aimed to assess the real-world costs of manual thrombectomy (MT)
      in selected ST-segment elevation myocardial infarction patients with
      intracoronary thrombus (IT). METHODS: Study group (IT+) comprised 51 patients
      with MT applied and control group (IT-) comprised 56 patients without IT who
      underwent angioplasty alone. Costs comprised hospital care and cost of disposable
      materials used during primary angioplasty. RESULTS: Complex management of
      patients with IT is more expensive, though allows to achieve clinical outcomes
      comparable to low-risk ST-segment elevation myocardial infarction patients
      without IT. CONCLUSION: A complex pharmaco-interventional strategy, with
      glycoprotein IIB/IIIA inhibitor and MT, though more expensive, may prove cost
      effective.

PMID- 29376403
TI  - Role of Subtalar Arthroscopy in Operative Treatment of Sanders Type 2 Calcaneal
      Fractures Using a Sinus Tarsi Approach.
AB  - BACKGROUND: This study was conducted to evaluate the usefulness of subtalar
      arthroscopy in the operative treatment of Sanders type 2 calcaneus fractures
      using a sinus tarsi approach. METHODS: Forty-six Sanders type 2 calcaneal
      fractures were consecutively treated using a sinus tarsi approach. Intraoperative
      fluoroscopy was used to evaluate fracture reduction in the first 23 patients
      (fluoroscopy group), and intraoperative fluoroscopy and subtalar arthroscopy were
      used in the latter 23 patients (arthroscopy group). Clinical evaluations were
      performed using a visual analog scale, the Ankle-Hindfoot Scale developed by the
      American Orthopaedic Foot & Ankle Society, and Short Form Health Survey.
      Radiographic evaluations were performed using calcaneal and lateral radiographs
      and computed tomography (CT) scans. Bohler's angles and calcaneal widths were
      compared between the groups. Reduction of the posterior facet was graded
      according to articular step, defect, and angulation of the posterior facet on CT.
      RESULTS: At the last follow-up, clinical results as well as Bohler's angles and
      calcaneal widths were not different between the groups. On immediately
      postoperative CT, reduction of the posterior facet showed a higher-than-good
      grade in 17 feet (73.9%) in the fluoroscopy group and a higher-than-good grade in
      22 feet (95.7%) in the arthroscopy group, and these values were significantly
      different between the groups ( P = .04). CONCLUSION: A combined approach using
      fluoroscopy and subtalar arthroscopy showed better reduction of the posterior
      facet on CT than using fluoroscopy alone. Therefore, subtalar arthroscopy could
      be a useful method for detecting joint incongruence when using the sinus tarsi
      approach for Sanders type 2 calcaneal fractures. LEVEL OF EVIDENCE: Level III,
      comparative series.

PMID- 29376404
TI  - A new benzofuran from the heartwood of Dalbergia latifolia.
AB  - A new benzofuran compound, named 2-[5-hydroxy-4-methoxy-2-(3-p-henyl-trans
      allyloxy)benzyl]-5-hydroxy-6-methoxy-3-phenylbenzofuran (1), together with (+)
      obtusafuran (2) and isoparvifuran (3), was isolated from the heartwood of
      Dalbergia latifolia. Their structures were elucidated by a combination of
      spectroscopic methods and comparison with the literature. Compounds 2 and 3 were
      obtained from this plant for the first time. Compound 1 exhibited moderated
      antioxidant effect for scavenging 1,1-diphenyl-2-picryhydrazyl (DPPH) free
      radical (IC50 = 96.7 +/- 8.9 MUM).

PMID- 29376405
TI  - A new cyclohexenone from the tin mine tailings-derived fungus Aspergillus flavus
      YIM DT 10012.
AB  - A new cyclohexenone, named phomaligol D (1), together with two known compounds,
      kojic acid (2) and phomaligol A (3) were isolated from the tin mine tailings
      derived fungus Aspergillus flavus YIM DT 10012. Their structures were elucidated
      by detailed analysis of spectroscopic data.

PMID- 29376406
TI  - CT-Based Descriptive Classification for Residual Talar Defects Associated With
      Failed Total Ankle Replacement: Technique Tip.

PMID- 29376407
TI  - Investigation of chemical constituents of safflower and their tyrosinase
      inhibitory activity.
AB  - Investigation on bioactive chemical constituents of safflower led to the
      isolation of 10 compounds from the aqueous extract, including a new alkaloid (1),
      a new glucopyranoside (2), and 8 known compounds (3-10). The structures of two
      new compounds were elucidated on the basis of extensive spectral analyses,
      including 1D, 2D-NMR and HRESIMS. Biological research on the isolates indicated
      that compounds 3, 4 and 9 remarkably inhibited tyrosinase with IC50 at 0.11, 0.20
      and 0.11 mM, respectively, compared with the positive control arbutin (0.26 mM).
      To investigate the interaction between enzyme and isolated compounds, an in
      silico docking study was carried out. The research provided valuable experience
      for phytochemistry and biological investigation on safflower.

PMID- 29376408
TI  - Constructing narratives to describe video events using aided communication.
AB  - Narratives are a pervasive form of discourse and a rich source for exploring a
      range of language and cognitive skills. The limited research base to date
      suggests that narratives generated using aided communication may be structurally
      simple, and that features of cohesion and reference may be lacking. This study
      reports on the analysis of narratives generated in interactions involving aided
      communication in response to short, silent, video vignettes depicting events with
      unintended or unexpected consequences. Two measures were applied to the data: the
      Narrative Scoring Scheme and the Narrative Analysis Profile. A total of 15
      participants who used aided communication interacted with three different
      communication partners (peers, parents, professionals) relaying narratives about
      three video events. Their narratives were evaluated with reference to narratives
      of 15 peers with typical development in response to the same short videos and to
      the narratives that were interpreted by their communication partners. Overall,
      the narratives generated using aided communication were shorter and less complete
      than those of the speaking peers, but they incorporated many similar elements.
      Topic maintenance and inclusion of scene-setting elements were consistent
      strengths. Communication partners offered rich interpretations of aided
      narratives. Relative to the aided narratives, these interpreted narratives were
      typically structurally more complete and cohesive and many incorporated more
      elaborated semantic content. The data reinforce the robust value of narratives in
      interaction and their potential for showcasing language and communication
      achievements in aided communication.

PMID- 29376409
TI  - Social and structural determinants of HIV treatment and care among black women
      living with HIV infection: a systematic review: 2005-2016.
AB  - Black/African American (black) women comprised 59% of women living with HIV at
      the end of 2014 and 61% of HIV diagnoses among women in 2015. Black women living
      with HIV infection (BWLH) have poorer health outcomes compared with women of
      other races/ethnicities; social and structural determinants are often cited as
      barriers and facilitators of care. The objective of this qualitative review was
      to identify social and structural barriers and facilitators of HIV treatment and
      care among BWLH. The systematic review was conducted in six-stages using
      databases such as PubMed, PsycINFO, and Google Scholar: 1) searched for studies
      that enrolled BWLH published between January 2005 and December 2016, 2) excluded
      unpublished reports and commentaries, 3) limited the search to our primary
      keywords, 4) limited our search to studies that included participants living with
      HIV infection that were >60% black and 100% female, 5) extracted and summarized
      the data, and 6) conducted a contextual review to identify common themes. Of 534
      studies retrieved, 16 were included in the final review. Studies focused on: ART
      medication adherence (n = 5), engagement/retention in care (n = 4), HIV care and
      treatment services (n = 3), viral suppression (n = 1), and addressing multiple
      HIV care outcomes (n = 3). Main barrier themes included lack of family and/or
      social support, poor quality HIV services, and HIV-related stigma, particularly
      from healthcare providers; facilitator themes included resilience, positive
      relationships between case management and support services, high racial
      consciousness, and addressing mental health. Interventions that decrease these
      noted barriers and strengthen facilitators may help improve care outcomes for
      BWLH. Also, more HIV stigma-reduction training for healthcare providers may be
      warranted.

PMID- 29376410
TI  - Mode of physical activity participation by body mass index: 2015 behavioural risk
      factor surveillance system.
AB  - Body mass index (BMI) continues to be used as a marker of health due its strong
      correlation with adiposity and health. Physical activity (PA) has been shown to
      be favourably associated with a desirable BMI. Few studies have examined mode of
      PA participation across BMI indices with a mutually exclusive underweight BMI
      range. The purpose of this study was to examine the relationship between modes of
      PA and BMI. Data from the 2015 Behavioral Risk Factor Surveillance System was
      analysed. Underweight, overweight, and obese BMI categories possessed 35, 20, and
      46% lower odds of meeting current PA guidelines. The obese BMI group was found to
      have lower odds of meeting the aerobic only and strength only guidelines.
      Underweight, overweight, and obese groups possessed 63, 18, and 76% greater odds
      of meeting neither PA guideline, respectively.

PMID- 29376411
TI  - Policies and perceptions on generic drugs: The case of Greece.
AB  - The increase in the consumption of generic drugs to reduce pharmaceutical
      expenditure is a challenge for many countries, especially during the economic
      crisis. The purpose of the present study is to review the Greek market of generic
      drugs and the decisions that shape it, to determine the factors that affect Greek
      patients' and doctors' attitudes about generic substitution and present a set of
      measures for all stakeholders based on the findings of the secondary and primary
      analysis. The study includes (a) an analysis of international and national
      reports and legislation on drugs policies and (b) a questionnaire survey of 242
      hospital patients and 85 doctors regarding their perceptions on generics. A small
      increase in the volume of generics is recorded, yet not followed by sales value,
      over the recent years that the measures for promoting generics prescription took
      effect. Distrust from both patients and doctors was observed toward generics'
      effectiveness and toward the appropriateness of the regulatory authorities'
      quality controls. The study presents a structured set of viable measures,
      applicable to many countries, for promoting generic drug consumption that can
      lead to economic efficiency without degrading the health care quality.

PMID- 29376412
TI  - Patient empowerment: Its implementation and systems within hospitals in England
      and Greece.
AB  - INTRODUCTION: International health policies recognise patient empowerment,
      resulting in diverse empowerment models and systems. Research on organisational
      systems for implementing patient empowerment between countries or from
      organisational stakeholders' perspective, however, is limited. Aims and
      methodology: This paper explores and compares organisational systems and
      structures for patient empowerment implementation in six acute public hospitals
      in England and Greece (three in each country), their cross-case and cross
      national similarities and differences. It uses a comparative, qualitative,
      explanatory embedded case study design. Semi-structured interviews with a
      representative sample of stakeholders (n = 33) and documentary sources (n = 79)
      were analysed with framework. RESULTS: Two main patient empowerment themes were
      identified: (1) organisational leadership, systems, structures; (2) operational
      structures, services, mechanisms and activities. Generic organisational systems
      and structures for patient empowerment varied across-cases, but with common
      organisation of empowerment roles in England and common leadership in Greece.
      Operational structures, services and mechanisms supporting empowerment varied
      across-cases and cross-nationally, but with similarities in the main services.
      CONCLUSION: Implementation of patient empowerment was weaker in Greece than in
      England, attributable to differing approaches to strategic and operational
      leadership, limited development of strategies and influential organisational
      structures. Overall, patient empowerment is well-embedded in organisations with a
      highly visible patient empowerment profile; commitment to policies and strategy
      implementation at different levels; strategic and operational leadership
      investing in dedicated roles with clear authority for patient empowerment,
      influential empowerment structures and mechanisms.

PMID- 29376413
TI  - A case report and a literature review of primary retroperitoneal mucinous
      cystadenoma: the importance of imaging in diagnosis and management.
AB  - Primary retroperitoneal mucinous cystadenoma (PRMC) is an extremely rare tumor:
      its histogenesis and its biological behavior remain speculative. Since most
      retroperitoneal tumors are malignant, a preoperative diagnosis of benignity is
      essential and it can be reached through imaging examinations, allowing a
      conservative management approach. We describe the case of a 52-year-old woman
      with abdominal pain and a palpable mass. Computed tomography of the abdomen
      revealed a retroperitoneal cystic mass, which was resected successfully through
      laparoscopy and diagnosed as PRMC. Although there are no pathognomonic, clinical
      or radiological findings for PRMC, it should be included in the list of
      differential diagnoses and its imaging criteria of benignity should always be
      sought, with the aim to exclude malignant tumors.

PMID- 29376414
TI  - Perceptions of control and improved psychological, physical, and social
      functioning in postmenopausal women.
AB  - Throughout life, social messages about women's bodies put them at greater risk of
      specific psychological health conditions than men; yet little is known about what
      psychological factors can help promote mental health in older women. In this
      study, we examine how perceptions of control relate to perceptions of
      psychological health, in addition to physical health, and social functioning in a
      sample of postmenopausal women. Results suggest that increased perceptions of
      control relate to improved perceptions of health via a reduction in negative
      affect. Implications for promoting health and reducing gendered mental health
      disparities are discussed.

PMID- 29376415
TI  - LC-ESI-MS/MS and cytotoxic activity of three Pistacia species.
AB  - LC-ESI-MS/MS was used for a comprehensive characterisation of ethanol extract
      from the leaves of three Pistacia species. After optimisation of the method and
      the use of the negative ionisation mode, a total of 42 different compounds were
      identified, of which 22 were tentatively characterised in P. chinensis Bunge, 33
      in P. khinjuk stocks and 25 in P. lentiscus L. leaves. Flavonoids, phenolic
      acids, and their derivatives were the most abundant identified compounds. LC-ESI
      MS/MS revealed identification of 15, 18 and 6 not previously detected compounds
      in P. chinensis Bunge, P. khinjuk Stocks and P. lentiscus L., respectively. The
      three extracts were also tested for their cytotoxic activities against human PC3
      prostate cancer, A549 lung cancer, MCF7 breast cancer and HepG2 liver cancer.
      Generally, all the extracts have a moderate cytotoxic activity against lung,
      breast and prostate cancer, with different IC50. However, only P. lentiscus L.
      showed moderate activity against liver cancer.

PMID- 29376416
TI  - Influence of well-being variables and recovery state in physical enjoyment of
      professional soccer players during small-sided games.
AB  - This study aimed to assess the effects of the total quality of recovery and well
      being indices (self-ratings of sleep during the preceding night, stress, fatigue
      and delayed onset muscle soreness) on rating of perceived exertion (RPE) and
      physical enjoyment (PE) during small-sided games. A total of 20 professional
      soccer players (25 +/- 0.8 years) completed four 5-a-side game sessions of 25-min
      duration each (4 * 4 min work with 3-min passive recovery in-between). All
      variables were collected before each game session with the exception of RPE and
      Physical Activity Enjoyment Scale that were collected after. The results
      demonstrate that recovery state and pre-fatigue states were not contributing
      signals of affected internal intensity and enjoyment of players. The study
      established the objectivity and utility of RPE as a useful tool for determining
      internal intensity during soccer-specific training as well as PE for assessing
      emotional response during exercise or training session.

PMID- 29376417
TI  - Adhesion of Legionella pneumophila on glass and plumbing materials commonly used
      in domestic water systems.
AB  - We aimed to investigate the adhesion of Legionella pneumophila serogroup1 and L.
      pneumophila serogroup2-15 on glass, galvanized steel, stainless steel, copper,
      Polyvinyl chloride(PVC), Cross-linked polyethylene(PEX-c) and Polypropylene
      Random Copolymer(PPR). The surface physicochemical properties of both bacterial
      cells and materials were estimated through contact angle measurements. The
      roughness and surface topography of the materials were evaluated by Atomic Force
      Microscopy. The two L. pneumophila serogroups and plumbing materials showed a
      hydrophobic character, while glass surface was hydrophilic. All strains were
      adhered to all materials with the exception of copper. The result showed that the
      adhesion of both L. pneumophila sg1 and sg2-15 was systematically expressed with
      high intensity on galvanized steel followed by PVC, PEX-c, PPR, stainless steel
      and the low intensity on glass. The extent of adhesion is in correlation with the
      surface roughness and acid-bases interactions, while hydrophobicity seems to have
      no effect in adhesion intensity.

PMID- 29376418
TI  - Growth and liver histology of Channa punctatus exposed to a common biofertilizer.
AB  - Mustard oil cake (MOC) is widely used as biofertilizer in the field of
      agriculture and aquaculture. Channa punctatus was exposed to 0.42 g.L-1 sublethal
      concentration for 4, 7, 14, 21 and 28 days. Due to such exposure, body growth and
      histological changes in liver were observed. It was revealed that weight, length
      and breadth of fish were gradually increased with the days of exposure in compare
      to control fish, whereas, liver showed an increase in sinusoidal space and
      lipidosis during early days, followed by a recovery from the stress of MOC on the
      28th day.

PMID- 29376419
TI  - Rosmarinic acid protects on rat bone marrow mesenchymal stem cells from hydrogen
      peroxide-induced apoptosis.
AB  - To investigate the anti-oxidant activities and mechanism of rosmarinic acid (RA)
      on rat bone marrow mesenchymal stem cells (rBMSCs) from ischemia-induced
      apoptosis in vitro, which was established using H2O2-damage and analyzed for cell
      viability, cell apoptosis, ROS, morphological changes, and levels of apoptosis
      proteins. Pretreatment with RA significantly suppressed the generation of ROS,
      protected the morphological changes of cells, decrease the ratio of cell
      apoptosis, down-regulated the level of caspase-3, caspase-9, Bax/Bcl-2, and up
      regulated the level of p-PI3K. These findings suggest that RA may protect rBMSCs
      from H2O2-induced apoptosis by partly regulating PI3K/Akt signaling pathway and
      can be developed as a potential anti-apoptotic agent for therapy in
      cardiovascular diseases.

PMID- 29376420
TI  - Development and preliminary validation of a scale to measure patient uncertainty:
      The "Uncertainty Scale".
AB  - Research suggests that patient uncertainty related to experiencing symptoms may
      drive decisions to seek care. The only validated measure of patient uncertainty
      assesses uncertainty related to defined illness. In prior work, we engaged
      patients to describe uncertainty related to symptoms and used findings to develop
      the 'U-Scale' scale. In this work, we present results from preliminary scale
      reliability and validity testing. Psychometric testing demonstrated content
      validity, high internal consistency, and evidence for concurrent validity. Next
      steps include administration in diverse populations for continued refinement and
      validation, and exploration of the potential contribution of uncertainty to
      healthcare utilization.

PMID- 29376421
TI  - Comments on "Transcutaneous electrical nerve stimulation improves walking
      capacity and reduces spasticity in stroke survivors: a systematic review and meta
      analysis".

PMID- 29376423
TI  - [Pathophysiology, clinical and experimental possibilities of pericardial
      tamponade].
AB  - Acute pericardial tamponade is one of the most emergent clinical scenarios in
      cardiac surgery. With numerous causes in the background, pericardial tamponade
      can lead to cardiogenic shock and death. In modern diagnostic era, the
      recognition of pericardial tamponade is simple, but its management and the long
      term effects can still be challenging. Without the detailed understanding of the
      pathophysiological pathways diagnostic and therapeutic management plans of
      pericardial tamponade is very difficult. The aim of this review was to give a
      complex picture of pericardial tamponade, from its role in medical history to
      pathophysiology and its significance in surgical experimental models. Orv Hetil.
      2018; 159(5): 163-167.

PMID- 29376424
TI  - [The potential role of oscillometric devices for ankle-brachial index
      measurements in clinical practice].
AB  - INTRODUCTION: Oscillometric devices in contrast to the traditional Doppler based
      method for ankle-brachial index measurements have promising advantages like no
      need for special training, faster performance, and operator independence. AIM:
      Comparative assessment of the oscillometric and Doppler-based ankle-brachial
      index measurement. METHOD: Ankle-brachial index measurements were performed by
      continuous wave Doppler and an automatic oscillometric device (BOSO ABI-system
      100) in consecutive subjects. The comparative assessment was performed by Bland
      Altman and ROC analysis. RESULTS: The two kinds of measurements (734
      measurements) showed a good agreement in the ankle-brachial index spectrum close
      to the cut-off value of 0.9. The agreement diminished below or above this value.
      The optimal oscillometric ankle-brachial index diagnostic cut-off value was 0.96.
      CONCLUSIONS: The oscillometric device is not interchangeable for Doppler devices
      in the whole ankle-brachial index spectrum. Nevertheless, owing to its
      discriminative power, the oscillometric measurement potentially has an efficient
      role in the screening of asymptomatic patients. Orv Hetil. 2018; 159(5): 176-182.

PMID- 29376425
TI  - [Hungarian health resource allocation from the viewpoint of the English
      methodology].
AB  - INTRODUCTION AND AIM: This paper describes both the English health resource
      allocation and the attempt of its Hungarian adaptation. METHOD: We describe
      calculations for a Hungarian regression model using the English 'weighted
      capitation formula'. RESULTS: The model has proven statistically correct. New
      independent variables and homogenous regional units have to be found for Hungary.
      CONCLUSION: The English method can be used with adequate variables. Hungarian
      patient-level health data can support a much more sophisticated model. Further
      research activities are needed. Orv Hetil. 2018; 159(5): 183-191.

PMID- 29376426
TI  - [Systemic mastocytosis with progressive disease course].
AB  - Authors report on a case of a male patient of systemic mastocytosis that was
      associated with extensive cutaneous lesions. Chronic diarrhoea worsening his
      quality of life was well managed by the administration of antihistamines. The
      pleural fluid recurrence soon after drainage has been controlled by the
      administration of alpha interferon. 40 years after the onset of the first skin
      signs progression has been manifested in the development of "B" (bone marrow
      infiltration rate >30%, dysmyelopoiesis, serum tryptase >20 MUg/L, hepato- and
      splenomegaly) and "C" symptoms (liver function test abnormalities, cytopenia,
      malabsorption, osteoporosis). The patient died at age of 87. The authors' aim was
      to attract attention on this rare disease and emphasize that symptomatic therapy
      with antihistamines and drugs available based on customised rights by the
      National Health Insurance Fund might provide good quality of life. Orv Hetil.
      2018; 159(5): 192-196.

PMID- 29376428
TI  - Green synthesis and antioxidant activity of novel series of benzofurans from
      euparin extracted of Petasites hybridus.
AB  - A novel class of benzofuran derivatives is prepared from the isocyanide-based
      MCR, euparin and aldehydes in the presence of ZnO-nanorods as a catalyst in
      excellent yields at room temperature under solvent-free conditions as a green
      reaction medium. Also, the antioxidant activities of some synthesised compounds
      such as 4a, 4b, 10a and 10b were evaluated by DPPH radical scavenging and ferric
      reduction activity potential (FRAP) assays. Compound 10b, was shown moderate
      radical scavenging activity and very good reducing activity compared to standards
      (BHT and TBHQ).

PMID- 29376427
TI  - [The role of apolipoprotein M and sphingosine 1-phosphate axis in the prevention
      of atherosclerosis].
AB  - Previous studies showed that plasma levels of high-density lipoprotein (HDL)
      cholesterol are inversely related to risk of cardiovascular diseases. However, in
      the last few decades it became obvious that beyond its plasma level, HDL
      structure and function have a critical role in its anti-atherogenic efficacy.
      Apolipoprotein M (ApoM) is an HDL-associated plasma protein affecting HDL
      metabolism and exhibits various anti-atherosclerotic functions, such as
      protection against oxidation and regulation of cholesterol efflux. Sphingosine 1
      phosphate (S1P) is a potent sphingolipid mediator that regulates numerous
      cellular responses including cell differentiation and migration, apoptosis and
      vascular inflammation. The majority of S1P is associated to ApoM containing HDL
      particles. Therefore, ApoM and S1P content of HDL have an impact on the
      atherosclerotic process. Moreover, HDL-ApoM and S1P content can be altered in
      several pathologic conditions such as coronary artery disease. This review covers
      the currently available data on the contribution of ApoM and S1P to HDL function
      in health and cardiovascular diseases. Orv Hetil. 2018; 159(5): 168-175.

PMID- 29376430
TI  - Modeling of quantitative relationships between physicochemical properties of
      active pharmaceutical ingredients and tensile strength of tablets using a boosted
      tree.
AB  - OBJECTIVES: The aim of this study was to explore the potential of boosted tree
      (BT) to develop a correlation model between active pharmaceutical ingredient
      (API) characteristics and a tensile strength (TS) of tablets as critical quality
      attributes. METHODS: First, we evaluated 81 kinds of API characteristics, such as
      particle size distribution, bulk density, tapped density, Hausner ratio, moisture
      content, elastic recovery, molecular weight, and partition coefficient. Next, we
      prepared tablets containing 50% API, 49% microcrystalline cellulose, and 1%
      magnesium stearate using direct compression at 6, 8, and 10 kN, and measured TS.
      Then, we applied BT to our dataset to develop a correlation model. Finally, the
      constructed BT model was validated using k-fold cross-validation. RESULTS:
      Results showed that the BT model achieved high-performance statistics, whereas
      multiple regression analysis resulted in poor estimations. Sensitivity analysis
      of the BT model revealed that diameter of powder particles at the 10th percentile
      of the cumulative percentage size distribution was the most crucial factor for
      TS. In addition, the influences of moisture content, partition coefficients, and
      modal diameter were appreciably meaningful factors. CONCLUSIONS: This study
      demonstrates that BT model could provide comprehensive understanding of the
      latent structure underlying APIs and TS of tablets.

PMID- 29376431
TI  - Plasma sE-cadherin and the plasma sE-cadherin/sVE-cadherin ratio are potential
      biomarkers for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      airway inflammation with endothelial dysfunction. Cadherins are adhesion
      molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s)
      cadherin is released from the cell surface by the effects of proteases including
      matrix metalloproteinases (MMPs). OBJECTIVE: The aim of this study was to examine
      the associations of sE-/sVE-cadherin levels in plasma with the development of
      COPD. METHODS: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked
      immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63
      healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7
      levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and
      12 control). RESULTS: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin
      ratios were significantly higher in COPD and SS than in HS and HN groups, while
      plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p <
      0.0001). sE-cadherin levels paralleled the severity of airflow limitation in both
      plasma (p < 0.01) and ELF (p < 0.05), while plasma sVE-cadherin levels were
      inversely correlated with the extent of emphysema (p < 0.05). MMP-7 levels were
      correlated with sE-cadherin levels in ELF. CONCLUSIONS: Plasma sE-cadherin levels
      and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.

PMID- 29376432
TI  - Modifications in drug adherence after switch to fixed-dose combination of
      perindopril/amlodipine in clinical practice. Results of a large-scale Italian
      experience. The amlodipine-perindopril in real settings (AMPERES) study.
AB  - OBJECTIVE: The purpose of this study was to assess the changes in adherence to
      treatment, in patients who switched from perindopril and/or amlodipine as a
      monotherapy (single-pill therapy, SPT) or two-pill combinations to fixed-dose
      combination (FDC) therapy. METHODS: A large retrospective cohort study, in three
      Italian Local Health Units, was performed. All adult subjects who received at
      least one prescription of anti-hypertensive drugs between January 1, 2010 and
      December 31, 2014 were selected. The date of the first anti-hypertensive
      prescription was defined as the index-date (ID). For each patient, we evaluated
      the anti-hypertensive therapy and the adherence to treatment during the two 12
      month periods preceding and following the ID. Changes in the level of adherence
      have been compared in patients who switched to the FDC of perindopril/amlodipine
      after the ID, as well as in patients who did not. RESULTS: A total of 24,020
      subjects were initially included in the study. Subjects treated with the free
      dose combination switched more frequently to FDC of perindopril/amlodipine than
      subjects treated with SPT (p < .001). Adherence to treatment was found to be
      higher in the 3,597 subjects who switched to the perindopril/amlodipine FDC
      therapy, than in the 20,423 subjects who did not. A significant decrease in the
      number of concomitant anti-hypertensive drugs has been observed in patients
      treated with the same FDC. CONCLUSIONS: The results show that
      perindopril/amlodipine FDC increases the rate of stay-on-therapy and reduces the
      number of concomitant anti-hypertensive drugs in subjects previously treated with
      the same drugs as a two-pill combination or as SPT.

PMID- 29376433
TI  - Process, optimization, and characterization of budesonide-loaded nanostructured
      lipid carriers for the treatment of inflammatory bowel disease.
AB  - The major challenge involved in the treatment of inflammatory bowel disease is
      targeted delivery of the drug at the site of inflammation. As nanoparticles
      possess the ability to accumulate at the site of inflammation, present
      investigation aims at development of Budesonide-loaded nanostructured lipid
      carrier systems (BDS-NLCs) for the treatment of inflammatory bowel disease. BDS
      NLCs were prepared by employing a high pressure homogenization technique. Various
      preliminary trials were performed for optimization of the NLCs in which different
      processes, as well as formulation parameters, were studied. The BDS-NLCs was
      optimized statistically by applying a 3-factor/3-level Box-Behnken design. Drug
      concentration, surfactant concentration, and emulsifier concentration were
      selected as independent variables, and % entrapment efficiency and particle size
      were selected as dependent variables. The best batch comprises of 10%, 7%, and
      20% w/w concentration of drug, surfactant, and emulsifier, respectively, with %
      entrapment efficiency of 92.66 +/- 3.42% and particle size of 284.0 +/- 4.53 nm.
      Further, in order to achieve effective delivery of nanoparticulate system to
      colonic region, the developed BDS-NLCs were encapsulated in Eudragit(r) S100
      coated pellets. The drug release studies of pellets depict intactness of BDS-NLCs
      during palletization process, with f2 value of 75.879. The in vitro evaluation of
      enteric-coated pellets revealed that a coating level of 15% weight gain is needed
      in order to impart lag time of 5 h (transit time to reach colon). The results of
      the study demonstrate that the developed BDS-NLCs could be used as a promising
      tool for the treatment of inflammatory bowel disease.

PMID- 29376434
TI  - Exercise and cognitive function in people living with HIV: a scoping review.
AB  - BACKGROUND: Since the advent of antiretrovirals, people with HIV are living
      longer and have improved quality of life. However, 30-60% of these individuals
      experience cognitive impairment. Fortunately, physical activity has emerged as a
      management strategy for cognitive impairment. PURPOSE: To map the evidence on
      physical activity and cognition in HIV. METHODS: We searched five databases using
      terms related to physical activity and HIV. Two authors independently reviewed
      titles and abstracts for studies that addressed physical activity/exercise and
      cognition in people with HIV. Authors reviewed full texts to identify articles
      that met our inclusion criteria. One author extracted the data, then we collated
      the results and summarized the characteristics of included studies. RESULTS:
      Sixteen studies from high-income countries were included; eight were
      interventional (five randomized controlled trials and three pre-post single group
      observational studies) and eight were non-interventional studies. The
      interventional studies included aerobic, resistive, and Tai Chi exercise for 8
      weeks to 12 months in duration. Two of eight interventional studies found
      exercise to benefit self-reported cognition. All eight non-interventional studies
      showed a positive relationship between physical activity and cognitive function.
      CONCLUSIONS: Results of this study suggest that physical activity may preserve or
      improve cognition in people living with HIV. Implications for Rehabilitation
      Physical activity may play a role in preserving or improving cognition in the
      human immunodeficiency virus population. Exercise should be prescribed for people
      with human immunodeficiency virus based on the stage of infection. Rehabilitation
      professionals should follow current exercise guidelines when prescribing exercise
      for people living with human immunodeficiency virus.

PMID- 29376435
TI  - Insights into future therapeutics for atopic dermatitis.
AB  - INTRODUCTION: Atopic Dermatitis (AD) is a common chronic inflammatory skin
      disorder with a constellation of symptoms. Currently, there are numerous
      therapies in various phases of drug development that target the pathogenesis of
      AD. Areas covered: Our paper aims to examine small molecule therapies and other
      novel agents registered for clinical trial in the phase II and mainly phase III
      stages of development. A literature search using PubMed as well as
      Clinicaltrials.gov was conducted. Clinical trial evidence of these novel agents
      was compiled and assessed. Both topical and oral novel therapies with diverse
      range of mechanistic action are currently being studied, with varying success.
      These include phosphodiesterase-4 inhibitors, boron molecules, Janus kinase
      inhibitors, cannabinoid receptors agonists, kappa-opioid receptor agonists. A
      variety of compounds with yet undisclosed or unknown mechanisms of action are
      also being studied. Expert opinion: Further research through extensive clinical
      trials will allow for more information about these targeted therapies and their
      potential place in the treatment algorithm of AD. Due to the success of such
      therapies in treating a spectrum of chronic inflammatory diseases, we remain
      hopeful that the successful development of targeted therapy for AD lies ahead.

PMID- 29376436
TI  - Efficacy and safety of plecanatide in treating constipation predominant irritable
      bowel syndrome.
AB  - INTRODUCTION: Uroguanylin interacting with intestinal Guanylate Cyclase C (GC-C)
      receptors plays an important role in gastrointestinal fluid and electrolyte
      homeostasis. Plecanatide is the first uroguanylin analog that stimulates GC-C
      receptors on gastrointestinal mucosa with pH-sensitive receptor binding. Binding
      to the GC-C receptor activates intracellular conversion of GTP to cGMP resulting
      in the stimulation of intestinal fluid secretion. Areas covered: Herein, all
      published research regarding the development of and clinical experience with
      plecanatide is reviewed. Clinical study results in patients with Chronic
      Idiopathic Constipation (CIC) and Irritable Bowel Syndrome with Constipation (IBS
      C) are also reviewed. Success in the treatment of CIC and IBS-C is supported by
      beneficial effects on stool viscosity, Complete Spontaneous Bowel Movements and
      visceral sensation. Finally, the discussion within focuses on the importance of
      plecanatide in understanding the physiology of uroguanylin, the pathophysiology
      of IBS-C and the potential for development of uroguanylin and guanylin analogs.
      Expert opinion: Given this broad spectrum of potential activity for GC-C
      agonists, it would not be surprising to see that the use of agents such as
      plecanatide in new areas grow to a level even greater than the use for the
      present CIC and IBS-C indications.

PMID- 29376437
TI  - Hematopoietic stem cell transplant in adults with acute lymphoblastic leukemia:
      the present state.
AB  - INTRODUCTION: Allogeneic hematopoietic stem cell transplant (allo-HSCT) has an
      important role in management of acute lymphoblastic leukemia (ALL). Proper
      patient selection is central to ensure optimal outcomes. Areas covered: This
      review covers various aspects of HSCT in ALL patients, including indications,
      donor selection, conditioning regimens, and post-transplant management. Expert
      commentary: Allo-HSCT is important in post-remission management of ALL but proper
      risk-stratification is a major challenge. Incorporation of minimal residual
      disease (MRD) and molecular testing will improve patient allocation. Patients
      receiving pediatric-inspired induction who achieve molecular remission might not
      need allo-HSCT in first remission. Allo-HSCT should be considered in patients who
      don't achieve MDR negativity, didn't receive intensive induction, or have high
      risk cytogenetic and molecular features. Despite improved responses with tyrosine
      kinase inhibitors (TKIs) in Philadelphia positive (Ph+) ALL, allo-HSCT remains
      standard. Matched sibling donors are the optimal graft source, but other sources
      are valid alternatives. There is no single optimal conditioning regimen and
      retrospective studies found myeloablative and reduced intensity regimens to be
      comparable. Following allo-HSCT, there is no role for maintenance therapy in
      Philadelphia-negative ALL. In Ph+ ALL, maintenance TKIs improve outcomes. The
      integration of targeted and immunotherapies in the peri-transplant period holds
      potential for improved outcomes.

PMID- 29376438
TI  - N-methyl-D-aspartate receptor encephalitis: laboratory diagnostics and
      comparative clinical features in adults and children.
AB  - INTRODUCTION: N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most
      common autoimmune encephalitis due to autoantibodies against neuronal surface
      antigens, can affect both children and adults, leading to neurological and
      neuropsychological sequelae. However, it is potentially treatable and the prompt
      start of immunotherapy associates with better prognosis. Conversely, misdiagnosis
      can be harmful. The detection of NMDAR antibodies in serum and cerebrospinal
      fluid plays a pivotal role in the diagnostic work-up. Reliable methods for NMDAR
      antibody detection are thus fundamental to assure accurate diagnosis and allow
      early treatments. Areas covered: This review recapitulates the pathogenic
      mechanisms of NMDAR encephalitis as a model of antibody mediated synaptopathy,
      and gives insights into the related state-of-the-art laboratory testing. The
      differences in clinical presentations, tumor associations and responses to
      treatments between adults and children are also described. Expert commentary: The
      relevance of NMDAR encephalitis has placed neuroimmunology laboratories in a
      crucial position, but methods for NMDAR antibody detection are awaiting thorough
      and consensus-based standardizations. In the next few years, this process, along
      with novel insights into the pathogenic mechanisms, could improve the disease
      management and clarify the still pending role of NMDAR antibodies in healthy
      people and in other more common neuropsychiatric disorders.

PMID- 29376439
TI  - Pharmacotherapy for obesity in individuals with type 2 diabetes.
AB  - INTRODUCTION: Type 2 diabetes (T2DM) is associated with significant morbidity and
      mortality. Obesity is one of the main risk factors for T2DM and its management
      requires a multidisciplinary approach, which may include pharmacotherapy. Areas
      covered: In this paper, data on efficacy, tolerability and safety of FDA-approved
      pharmacotherapies for obesity (orlistat, phentermine/topiramate extended-release,
      lorcaserin, bupropion sustained release/naltrexone sustained release and
      liraglutide) are reviewed, focusing on individuals with type 2 diabetes. Expert
      opinion: Obesity is the major pathophysiologic driver of T2DM; conversely 5-10%
      weight loss leads to significant improvement in glycemic control, lipids and
      blood pressure. Weight loss maintenance is difficult with lifestyle interventions
      alone and may require adjunctive therapies. There is good evidence for the
      efficacy and tolerability of approved anti-obesity pharmacotherapies in
      individuals with T2DM, with current cardiovascular safety data being most
      favorable for liraglutide, orlistat and lorcaserin. Given the link between
      obesity and T2DM, a weight-centric therapeutic approach including use of weight
      reducing anti-diabetic therapies, and anti-obesity pharmacotherapies is both
      intuitive and rational to improve glycemic and other metabolic outcomes in
      patients with T2DM.

PMID- 29376440
TI  - Advances in cardiorespiratory physiotherapy and their clinical impact.
AB  - INTRODUCTION: Cardiorespiratory physiotherapy is an evidence-based practice that
      has evolved alongside changes in medical and surgical management, analgesia, the
      ageing society and increasing comorbidities of our patient populations. Continued
      research provides the profession with the ability to adapt to meet the changing
      patient and community needs. Areas covered: This review focuses on surgical,
      respiratory and critical care settings discussing the most significant changes
      over the past decade with an increased focus on rehabilitation across the care
      continuum and a shift away from providing predominately airway clearance in
      established disease populations but also providing this in emerging groups.
      Further important changes are identification and emphases on patient self
      management including changing their behaviour to more positively embrace
      wellness, particularly increasing physical activity levels. This paper outlines
      these changes and offers speculation on factors that may impact the profession in
      the future. Expert commentary: The increasing focus on new technologies, physical
      activity levels, changes to the health systems in different countries and an
      increasingly comorbid and ageing society will shape the next steps in the
      evolution of cardiorespiratory physiotherapy. Continued research is vital to keep
      pace with these changes so that physiotherapists can provide the most effective
      treatments to improve patient outcomes.

PMID- 29376441
TI  - Spontaneous haemorrhage into a large abducens nerve schwannoma: a case report.
AB  - PURPOSE: Abducens schwannomas are rare tumors that are not known to present with
      acute haemorrhage. We present a case of a 59 year-old female on warfarin who
      presented acutely with a sudden onset headache, nausea and photophobia.
      Neuroimaging revealed an acute haemorrhage into a lesion that entered Dorello's
      canal and was consistent with an abducens nerve schwannoma. MATERIALS AND
      METHODS: The patient's case notes, imaging, histology and operative recording
      were reviewed retrospectively to compile this case report. RESULTS: The tumor was
      resected via a retro-mastoid approach with sacrifice of the abducens nerve.
      Removal of the haematoma intra-operatively provided more space in the surgical
      corridor to facilitate resection. Final histological examination confirmed the
      diagnosis of schwannoma and the patient made a good post-operative recovery.
      CONCLUSION: We conclude that accurate pre-operative radiological diagnosis can
      facilitate surgical planning and removal of haematoma at an early stage during
      the operation can create space and facilitate resection. Furthermore, abducens
      schwannoma should be considered in the differential diagnosis of any heamorrhagic
      cerebello-pontine angle lesion.

PMID- 29376442
TI  - Drug delivery targets and systems for targeted treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease that
      selectively attacks human joints. The common non-targeted treatment approaches
      lead to obvious side effect and systemtic complication for RA patients.
      Therefore, targeted drug delivery for treatment of RA has gained much attetntion
      in the past few years. In this paper, we reviewed the potential targets (folate
      receptor, angiogenesis, matrix metalloproteases, selectins, vasoactive intestinal
      peptide receptor andFc-gamma receptor) that could be utilised to facilitate the
      specific delivery of drugs to the inflammed synovium and also presented different
      drug delivery systems for targeting RA, including the liposomes, various types of
      nanoparticles, polymeric micelles and the macromolecular prodrugs. The strategies
      combining nanotechnologies and ligand mediated active targeting for RA would be
      emphatically illustrated, which was expected to be helpful for identifying
      technologies and drug delivery methods for targeted treatment of RA.

PMID- 29376443
TI  - Old and new synthetic cannabinoids: lessons from animal models.
AB  - Synthetic cannabinoids have long been studied for their therapeutic potentials.
      However, during the last decade, new generations of synthetic cannabinoid
      agonists appeared on the drug market. These new psychoactive substances are
      currently sold as 'marijuana-like' products as they claim to mimic the effects of
      the psychoactive component of cannabis, delta-9-tetrahydrocannabinol (THC). Yet,
      their effects are more intense and potent than THC, typically last longer and are
      often associated to serious psychiatric consequences. Animal models of drug
      addiction are frequently used in preclinical research to assess the abuse
      potential of new compounds, evaluate drug positive reinforcing effects and
      analyze drug-induced behaviors. Some of these protocols have been used recently
      to study the newly synthesized cannabinoid agonists and have started elucidating
      their pharmacology and actions in the brain. The aim of this review is to
      summarize the major findings reported by animal studies that tested synthetic
      cannabinoids of first, second, and third generation by using self-administration
      and reinstatement models, drug discrimination and conditioned place preference
      procedures. Altogether, behavioral studies clearly indicate that synthetic
      cannabinoids possess abuse liability, are likely to activate the brain reward
      circuit and induce positive subjective and reinforcing effects.

PMID- 29376444
TI  - Hot-spot analysis for drug discovery targeting protein-protein interactions.
AB  - INTRODUCTION: Protein-protein interactions are important for biological processes
      and pathological situations, and are attractive targets for drug discovery.
      However, rational drug design targeting protein-protein interactions is still
      highly challenging. Hot-spot residues are seen as the best option to target such
      interactions, but their identification requires detailed structural and energetic
      characterization, which is only available for a tiny fraction of protein
      interactions. Areas covered: In this review, the authors cover a variety of
      computational methods that have been reported for the energetic analysis of
      protein-protein interfaces in search of hot-spots, and the structural modeling of
      protein-protein complexes by docking. This can help to rationalize the discovery
      of small-molecule inhibitors of protein-protein interfaces of therapeutic
      interest. Computational analysis and docking can help to locate the interface,
      molecular dynamics can be used to find suitable cavities, and hot-spot
      predictions can focus the search for inhibitors of protein-protein interactions.
      Expert opinion: A major difficulty for applying rational drug design methods to
      protein-protein interactions is that in the majority of cases the complex
      structure is not available. Fortunately, computational docking can complement
      experimental data. An interesting aspect to explore in the future is the
      integration of these strategies for targeting PPIs with large-scale mutational
      analysis.

PMID- 29376445
TI  - Exploring Australian speech-language pathologists' use and perceptions ofnon
      speech oral motor exercises.
AB  - PURPOSE: To explore Australian speech-language pathologists' use of non-speech
      oral motor exercises, and rationales for using/not using non-speech oral motor
      exercises in clinical practice. METHODS: A total of 124 speech-language
      pathologists practising in Australia, working with paediatric and/or adult
      clients with speech sound difficulties, completed an online survey. RESULTS: The
      majority of speech-language pathologists reported that they did not use non
      speech oral motor exercises when working with paediatric or adult clients with
      speech sound difficulties. However, more than half of the speech-language
      pathologists working with adult clients who have dysarthria reported using non
      speech oral motor exercises with this population. The most frequently reported
      rationale for using non-speech oral motor exercises in speech sound difficulty
      management was to improve awareness/placement of articulators. The majority of
      speech-language pathologists agreed there is no clear clinical or research
      evidence base to support non-speech oral motor exercise use with clients who have
      speech sound difficulties. CONCLUSIONS: This study provides an overview of
      Australian speech-language pathologists' reported use and perceptions of non
      speech oral motor exercises' applicability and efficacy in treating paediatric
      and adult clients who have speech sound difficulties. The research findings
      provide speech-language pathologists with insight into how and why non-speech
      oral motor exercises are currently used, and adds to the knowledge base regarding
      Australian speech-language pathology practice of non-speech oral motor exercises
      in the treatment of speech sound difficulties. Implications for Rehabilitation
      Non-speech oral motor exercises refer to oral motor activities which do not
      involve speech, but involve the manipulation or stimulation of oral structures
      including the lips, tongue, jaw, and soft palate. Non-speech oral motor exercises
      are intended to improve the function (e.g., movement, strength) of oral
      structures. The majority of speech-language pathologists agreed there is no clear
      clinical or research evidence base to support non-speech oral motor exercise use
      with clients who have speech sound disorders. Non-speech oral motor exercise use
      was most frequently reported in the treatment of dysarthria. Non-speech oral
      motor exercise use when targeting speech sound disorders is not widely endorsed
      in the literature.

PMID- 29376446
TI  - Linking of assessment scales for women with urinary incontinence and the
      International Classification of Functioning, Disability and Health.
AB  - PURPOSE: This study aimed to link the content of four most used questionnaires to
      assess the quality of life of women with urinary incontinence (International
      Consultation on Incontinence Questionnaire; King's Health Questionnaire;
      Incontinence Quality of Life Questionnaire and Bristol Female Urinary Tract
      Symptoms Questionnaire) with the International Classification of Functioning,
      Disability and Health (ICF). METHODS: Linking the questionnaires content and the
      ICF was performed by two independent reviewers, with an excellent concordance
      level (k = 0.941), using the method described by Cieza et al. RESULTS: A total of
      94 items were analyzed, in which 154 meaningful concepts were identified and
      linked to 48 ICF categories, of which 49% were from activities and participation
      component (d) and 36.8% from body functions (b). CONCLUSIONS: The scales are
      linked with the classification at different levels. The International
      Consultation on Incontinence Questionnaire was the most limited instrument.
      Bristol Female Urinary Tract Symptoms Questionnaire and Incontinence Quality of
      Life Questionnaire presented greater agreement with the ICF, but the concepts in
      their items are mostly linked to body functions, denoting a biomedical vision.
      King's Health Questionnaire demonstrated greater affinity with the ICF, and most
      concepts were related to the activities and participation categories, approaching
      more effectively the biopsychosocial model. Implications for Rehabilitation
      Choosing the right instrument to assess the quality of life of women with urinary
      incontinence can be a difficult task, since the instruments have different
      approaches. The use of International Classification of Functioning, Disability
      and Health as a reference among health professionals involved in rehabilitation
      of women with urinary incontinence will promote unification of the language about
      this group functioning. The comparison among instruments presented here will help
      the professional to choose the one that provides the greatest amount of
      information in a consistent way, aiding the clinical decision-making process.

PMID- 29376447
TI  - Characterizing disease-associated changes in post-translational modifications by
      mass spectrometry.
AB  - INTRODUCTION: Exploring post-translational modifications (PTMs) with the use of
      mass spectrometry (PTMomics) is a rapidly developing area, with methods for
      discovery/quantification being developed and advanced on a regular basis. PTMs
      are highly important for the regulation of protein function, interaction and
      activity, both in physiological and disease states. Changes in PTMs can either
      cause, or be the result of a disease, making them central for biomarker studies
      and studies of disease pathogenesis. Recently, it became possible to study
      multiple PTMs simultaneously from low amount of sample material, thereby
      increasing coverage of the PTMome obtainable from a single sample. Thus,
      quantitative PTMomics holds great potential to discover biomarkers from tissue
      and body fluids as well as elucidating disease mechanisms through
      characterization of signaling pathways. Areas covered: Recent mass spectrometry
      based methods for assessment of the PTMome, with focus on the most studied PTMs,
      are highlighted. Furthermore, both data dependent and data independent
      acquisition methods are evaluated. Finally, current challenges in the field are
      discussed. Expert commentary: PTMomics holds great potential for clinical and
      biomedical research, especially with the generation of spectral libraries of
      peptides and PTMs from individual patients (permanent PTM maps) for use in
      personalized medicine.

PMID- 29376448
TI  - Desmopressin and nocturnal voiding dysfunction: Clinical evidence and safety
      profile in the treatment of nocturia.
AB  - INTRODUCTION: Nocturia is a common urinary condition experienced by both men and
      women. While desmopressin has historically been utilized to treat conditions such
      as central diabetes insipidus and primary nocturnal enuresis, there is an
      increased interest in the use of desmopressin in the management of adult
      nocturia. Areas covered: This article provides a review on the pathophysiology of
      nocturia and the clinical outcomes and safety profile of desmopressin in the
      management of adult nocturnal voiding dysfunction. Expert opinion: To date,
      desmopressin is the only anti-diuretic hormone that is approved for nocturia.
      Published literature on desmopressin demonstrate good clinical efficacy in terms
      of number of nocturnal voids, voided volume and sleep period. Newer formulations
      have shown that a minimum dosage of 25 MUg orally disintegrating sublingual
      desmopressin appears to be ideal for women, whereas men usually benefit from a
      minimum of 50 MUg. Of the known adverse drug reactions, hyponatremia remains a
      major concern especially in patients over 65 years of age. At present, long term
      data on desmopressin remains scarce. Lastly, it is important to stress that no
      single treatment deals with nocturia in all contexts, and careful assessment
      remains essential to identify the appropriate and safest treatment in each
      patient.

PMID- 29376449
TI  - Folate receptor-targeted lipid-albumin nanoparticles (F-LAN) for therapeutic
      delivery of an Akt1 antisense oligonucleotide.
AB  - BACKGROUND: RX-0201 is an antisense oligonucleotide (ASO) against Akt1 currently
      in clinical trial for metastatic renal cancer. PURPOSE: To improve the delivery
      of RX-0201 using folate receptor-targeted lipid-albumin nanoparticles (F-LAN).
      METHODS: F-LAN were synthesized with the composition of DOTAP/soyPC/TPGS/folate
      PEG-DSPE (25:70:4:1 m/m), a cationic human serum albumin-pentaethylenehexamine
      (HSA-PEHA) conjugate and RX-0201. The nanoparticles were evaluated in KB human
      carcinoma cells in vitro and in a KB murine xenograft tumour model in vivo for
      pharmacokinetics and antitumor activities. RESULTS: The F-LAN-RX-0201 had a mean
      particle size of 108.6 +/- 5.8 nm, zeta potential of 10.5 +/- 3.2 mV and ASO
      loading efficiency of 71.5 +/- 4.5%. In KB cells, uptake and Akt1 inhibition by F
      LAN-RX-0201 were greater than those of non-targeted LAN-RX-0201 and could be
      partially blocked by excess free folate. F-LAN-RX-0201 inhibited cell growth with
      an IC50 of 11.9 MUM. In contrast, LAN-RX-0201 showed lower cytotoxicity with an
      IC50 of 32.0 MUM. No significant cytotoxicity was observed with up to 250 uM of
      free RX-0201. Pharmacokinetic studies showed that F-LAN-RX-0201 had a longer
      terminal half-life than free RX-0201 (442 vs. 219 min). In a KB xenograft tumour
      model, F-LAN-RX-0201 exhibited greater tumour inhibition than LAN-RX-0201 at 16
      mg/kg. Moreover, F-LAN-RX-0201 at 16 mg/kg showed comparable tumour inhibition
      compared to free RX-0201 at a much higher dose of 90 mg/kg. CONCLUSIONS: F-LAN-RX
      0201 showed promise as a therapeutic agent for tumours with elevated folate
      receptor expression.

PMID- 29376450
TI  - Barriers and facilitators to meeting aphasia guideline recommendations: what
      factors influence speech pathologists' practice?
AB  - PURPOSE: To explore factors influencing Australian speech pathologists' guideline
      recommended aphasia management practices. METHODS: Semi-structured interviews
      were conducted with hospital-based speech pathologists (n = 20). Interviews
      focused on barriers and facilitators to implementing recommendations related to
      five practice areas: Aphasia-friendly Information; Collaborative Goal Setting;
      Timing of Therapy; Amount and Intensity of Therapy; and Conversation Partner
      Training. RESULTS: Speech pathologists working only in inpatient rehabilitation
      settings reported performing the recommended behaviours consistently, and
      identified few implementation barriers. However, clinicians working in the acute
      setting reported performing the majority of behaviours inconsistently or rarely.
      Seven (of 14) Theoretical Domains Framework domains were identified as key
      influencing factors. Three of these - "Environmental Context and Resources,"
      "Beliefs about Consequences," and "Social Influences" - were consistently
      reported as influencing practice across all five behaviours. Other important
      domains included "Knowledge", "Beliefs about Capabilities," "Goals," and
      "Social/Professional Role and Identity", which each influenced at least two
      practice behaviours. CONCLUSIONS: Speech pathologists report a number of key
      factors influencing their practice, which differ in how they influence behaviours
      (i.e., a factor may be a barrier or a facilitator) depending on the behaviour and
      clinical setting. Future implementation interventions need to account for the
      strong influence of beliefs and social influences on speech pathology practice,
      which may facilitate successful implementation. Implications for rehabilitation
      Speech pathologists' aphasia management practices are often inconsistent with
      guideline recommendations. Environmental and contextual barriers were identified
      for all guideline-recommended practices that were investigated; however, these
      barriers did not necessarily impede implementation for speech pathologists
      working in inpatient rehabilitation settings. Strategies to improve both team
      functioning (social influences) and the belief systems of individual clinicians
      (beliefs about consequences) should be considered to improve speech pathologists'
      implementation of guideline-recommended aphasia practices.

PMID- 29376451
TI  - Infertile polycystic ovary syndrome patients undergoing in vitro fertilization
      with the gonadotropin-releasing hormone-antagonist protocol: role of
      hyperandrogenism.
AB  - This retrospective cohort study is to assess the effects of hyperandrogenism (HA)
      in polycystic ovary syndrome (PCOS) patients with gonadotropin-releasing hormone
      (GnRH)-antagonist protocol during in vitro fertilization (IVF). Total 892
      infertile Patients between 20 and 35 years of age with normal body mass index
      (BMI, 18.50 -24.99 kg/m2), including those with tubal factor infertility
      (control, n = 318), PCOS infertility with HA (HA PCOS, n = 244), and PCOS
      infertility without HA (non-HA PCOS, n = 330), were included. Number of retrieved
      oocytes was significantly higher and total Gonadotropin consumption was
      significant lower in the HA PCOS group, whereas abortion rate was significantly
      higher and live birth rate was significantly lower in the HA PCOS group, compared
      with the control and non-HA PCOS groups. In the HA PCOS group, the number of
      available embryos tended to be higher with no significance. The GnRH-antagonist
      protocol is more suitable for HA PCOS patients, with lower cost and more number
      of embryos available for transfer. Due to the high abortion rate and low live
      birth rate, a freeze-all approach might be a preferable option for HA PCOS
      patients so as to create a buffer for reducing androgen levels before
      transferring freeze-thawed embryos.

PMID- 29376452
TI  - Devices for ex vivo heart and lung perfusion.
AB  - INTRODUCTION: The number of organs available for heart and lung transplantation
      is far short of the number that is needed to meet demand. Perfusion and
      ventilation of donor organs after procurement has led to exciting advances in the
      field of cardiothoracic transplantation. The clinical implications of this
      technology allows for techniques to evaluate the quality of an organ, active
      rehabilitation of organs after procurement and prior to implantation, and
      increased time between organ procurement and implantation. This ex-vivo perfusion
      technique has also been referred to in the lay press as the 'heart in a box' or
      'lung in a box.' Areas covered: This review includes information from case
      reports, case series, and clinical trials on ex vivo heart and lung perfusion.
      The focus is on the devices, ventilation and perfusion techniques, outcomes, and
      application of the technology. Expert commentary: Ex vivo perfusion of donor
      hearts and lungs prior to transplantation has proven to be a viable alternative
      to standard cold-preservation strategies. Its use has allowed for ongoing
      expansion of the donor pool. The biggest barriers to expansion of this technology
      are access, cost, and lack of evidence which clearly supports superior outcomes.

PMID- 29376453
TI  - A large solitary fibrous tumour of the pleura: a case report and review of the
      literature.
AB  - We report a clinical case of a solitary fibrous tumour of the pleura (SFTP) in a
      67-year-old female patient complaining of chest pain for 2 months. A localized
      large mass was found in the left inferior hemithorax by computed tomography scan.
      The patient underwent a thoracotomy at the left side with endotracheal
      anaesthesia. During surgical resection, the tumour was located in the left
      inferior hemithorax and was attached to the inferior lobe of the left lung and
      diaphragmatic pleura by a fibrous pedicle. A wedge resection of the left lower
      lobe was undertaken to completely remove the tumour. Diagnosis of the SFTP was
      confirmed by the surgical findings and subsequent histological and
      immunohistochemical examinations. At the 6-month follow-up, no signs of local
      tumour recurrence or metastasis were documented. After a 3-year follow-up, this
      patient remains in good health.

PMID- 29376454
TI  - In vivo efficacy and evaluation of gel-cream containing dehydrated betamethasone
      dipropionate nanocapsules.
AB  - This study aimed to develop gel-creams from the lyophilised product of
      betamethasone dipropionate-loaded lipid-core nanocapsule suspensions and
      evaluated its efficacy in a model of contact dermatitis. The gel-creams were
      prepared and characterized followed by a study of in vitro drug
      penetration/permeation and its in vivo efficacy. The suspensions and lyophilised
      products showed nanometric size; the betamethasone content was 0.25 +/- 0.01
      mg/mL and the encapsulation efficiency was approximately 100%. The nanocapsules
      and redispersed powders presented control of the drug release. The gel-creams
      presented pH between 6.0-6.5 and exhibited non-Newtonian flow behavior, following
      the Herschel-Bulkley model. The skin penetration/permeation study indicated that
      betamethasone dipropionate can reach different skin layers. For in vivo efficacy,
      the contact dermatitis model was capable of causing tissue damage with changes in
      enzyme activities of the purinergic system in lymphocytes. The gel-creams showed
      the best dermatological and immunological efficacy and reduced oxidative damage
      in the evaluated tissues.

PMID- 29376455
TI  - Cyclodextrin-based nanosponges as vehicles for antiviral drugs: challenges and
      perspectives.

PMID- 29376456
TI  - Reduced spinal cord parenchymal cerebrospinal fluid circulation in experimental
      autoimmune encephalomyelitis.
AB  - An alteration of parenchymal cerebrospinal fluid circulation (CSF) has been
      proposed to take part in the pathophysiology of multiple sclerosis. By using an
      intragate T1-weighted high-resolution MRI of the spinal cord of freely breathing
      mice injected with a gadolinium chelate in the cisterna magna, we show that a
      parenchymal CSF circulation exists in the spinal cord, in addition to that
      originally described in the brain. In experimental autoimmune encephalomyelitis,
      a model of multiple sclerosis, we show a reduction of parenchymal CSF circulation
      specifically in the spinal cord but not in the brain.

PMID- 29376457
TI  - The Effect of the Presence of an Internet-Connected Mobile Tablet Computer on
      Physical Activity Behavior in Children.
AB  - BACKGROUND: Mobile Internet-connected electronic devices provide access to
      activities that have traditionally been associated with sedentary behavior.
      Because they are portable, these devices can be utilized in any environment.
      Therefore, providing children with access to these devices in environments that
      typically promote physical activity may result in a reduction in physical
      activity behavior. PURPOSE: To assess children's physical and sedentary (ie,
      sitting) activity with and without the presence of a mobile Internet-connected
      tablet computer. METHODS: A total of 20 children [6.7 (1.9) y old] participated
      in 2 simulated recess conditions in a gymnasium on separate days. During each
      condition, children had free-choice access physical activity options and a table
      of sedentary activities for 40 minutes. During 1 session, the iPad was present,
      and in the other session, it was not. Physical activity was monitored via an
      accelerometer, and sedentary time was monitored via a stopwatch. RESULTS:
      Children significantly (P <= .03) reduced average physical activity intensity and
      increased their sedentary behavior with the iPad present [4.4 (4.0) metabolic
      equivalents/min and 20.9 (12.4) min sitting] versus the condition without the
      iPad present [5.3 (4.0) metabolic equivalents/min and 13.6 (13.2) min sitting].
      CONCLUSION: Introducing an mobile Internet-connected tablet computer into a
      gymnasium reduced children's physical activity intensity by 17% and increased
      sedentary behavior by 54%.

PMID- 29376458
TI  - Does an in-house internist at a GP practice result in reduced referrals to
      hospital-based specialist care?
AB  - OBJECTIVE: Consistent evidence on the effects of specialist services in the
      primary care setting is lacking. Therefore, this study evaluated the effects of
      an in-house internist at a GP practice on the number of referrals to specialist
      care in the hospital setting. Additionally, the involved GPs and internist were
      asked to share their experiences with the intervention. DESIGN: A retrospective
      interrupted times series study. SETTING: Two multidisciplinary general
      practitioner (GP) practices. INTERVENTION: An internist provided in-house patient
      consultations in two GP practices and participated in the multidisciplinary
      meetings. SUBJECTS: The referral data extracted from the electronic medical
      record system of the GP practices, including all referral letters from the GPs to
      specialist care in the hospital setting. MAIN OUTCOME MEASURES: The number of
      referrals to internal medicine in the hospital setting. This study used an
      autoregressive integrated moving average model to estimate the effect of the
      intervention taking account of a time trend and autocorrelation among the
      observations, comparing the pre-intervention period with the intervention period.
      RESULTS: It was found that the referrals to internal medicine did not
      statistically significant decrease during the intervention period. CONCLUSIONS:
      This small explorative study did not find any clues to support that an in-house
      internist at a primary care setting results in a decrease of referrals to
      internal medicine in the hospital setting. Key Points An in-house internist at a
      primary care setting did not result in a significant decrease of referrals to
      specialist care in the hospital setting. The GPs and internist experience a
      learning-effect, i.e. an increase of knowledge about internal medicine issues.

PMID- 29376459
TI  - Two-tube method for treatment of spontaneous esophageal rupture and concomitant
      mediastinal infection.
AB  - Objective Spontaneous esophageal rupture (SER) is a rare but life-threatening
      condition with high mortality. The prognosis of patients with SER treated with
      surgical intervention or the traditional "three-tube" method is controversial.
      Thus, the aim of this study was to evaluate the clinical efficacy, feasibility,
      and safety of a new "two-tube" method involving a trans-fistula drainage tube and
      a three-lumen jejunal feeding tube for the treatment of SER without concomitant
      pleural rupture. Methods From January 2007 to June 2016, patients with SER and
      managed with the "two-tube" method or other methods were retrospectively
      analyzed. Data collected included initial presentation, procedure time, duration
      of treatment, numbers of patients with eventual healing of leaks, and
      complications. Results The average procedure time for the "two-tube" method was
      22.1 +/- 5.5 minutes. In comparison with the control method, the "two-tube"
      method had a similar diagnosis time (3.6 +/- 1.4 vs. 3.4 +/- 1.4 days) but a
      significantly higher successful closure rate (94.4% vs. 63.6%) and shorter
      treatment time (38.2 +/- 5.6 vs. 53.6 +/- 16.9 days). No complications associated
      with performance of the "two-tube" method occurred. Conclusion The "two-tube"
      method is an effective and safe approach for patients with SER.

PMID- 29376460
TI  - Anxiety disorders and CRP in a population cohort study with 54,326 participants:
      The LifeLines study.
AB  - OBJECTIVES: Growing evidence indicates that inflammatory processes may play a
      role in the pathogenesis of anxiety disorders. Nevertheless, much remains to be
      learned about the involvement of inflammation, including C-reactive protein
      (CRP), in specific anxiety disorders. This study examines the relation between
      anxiety disorders and CRP. METHODS: Associations of serum CRP with anxiety
      disorders were determined in a large population study (n = 54,326 participants,
      mean age = 47 years; 59% female), the LifeLines cohort. Depressive and anxiety
      disorders (generalized anxiety disorder, social anxiety phobia, panic disorder
      with or without agoraphobia and agoraphobia without panic disorder) were assessed
      using the Mini-International Neuropsychiatric Interview. RESULTS: Anxiety
      disorders, with the exception of social anxiety disorder, were significantly
      associated with increased CRP. After adjusting for demographics, life style
      factors, health factors, medication use, depression, and psychological stressors,
      CRP remained significantly associated with panic disorder with agoraphobia (beta
      = 0.01, P = .013). Moreover, CRP levels were significantly higher in people with
      panic disorder with agoraphobia compared to other anxiety disorders, independent
      of all covariates (F = 3.00, df = 4, P = .021). CONCLUSIONS: Panic disorder with
      agoraphobia is associated with increased CRP, although the effect size of this
      association is small. This indicates that neuroinflammatory mechanisms may play a
      potential role in its pathophysiology.

PMID- 29376461
TI  - The ability of liposomes, tailored for blood-brain barrier targeting, to reach
      the brain is dramatically affected by the disease state.
AB  - AIM: To investigate if and how the ability of liposomes, previously designed for
      Alzheimer's therapy, to reach the brain changes in aging/pathological conditions
      with respect to the healthy state. METHODS: Biodistribution and pharmacokinetics
      of liposomes in young or aged healthy mice and in an Alzheimer's mouse model were
      measured by radiochemical techniques. The expression of brain receptors and
      structural proteins was evaluated by Western blot. RESULTS: At equal blood
      levels, the amount and integrity of liposomes in the brain were dramatically
      lower in Alzheimer's or aged mice, with respect to young animals. These
      differences are likely attributable to molecular alterations in the brain
      vasculature. CONCLUSION: Brain alterations in pathology or aging should be
      considered in the design of drug delivery systems for brain targeting.

PMID- 29376462
TI  - Salivary cortisol as predictor for depression characteristics and remission in
      electroconvulsive therapy in older persons.
AB  - OBJECTIVES: Electroconvulsive therapy (ECT) is the most effective treatment for
      depression; however, consensus on predictors for ECT outcome is lacking. We aim
      to examine the relation between pre-ECT salivary cortisol values and clinical
      characteristics and ECT outcome in depressed, older persons. METHODS: A total of
      102 inpatients meeting DSM-IV criteria for depression and referred for ECT were
      selected. Salivary cortisol was assessed at five time points during the day,
      providing insight into the cortisol awakening curve to the ground (AUCg) and to
      the increase (AUCi) and evening cortisol level. Depression severity was assessed
      using the Montgomery-Asberg Depression Rating Scale (MADRS). Remission was
      defined as MADRS <10; response was defined as MADRS-reduction of at least 50%.
      Regression analysis was used to assess associations between cortisol and (1)
      clinical variables, including depression severity, psychomotor symptoms and
      presence of psychosis, and (2) ECT outcome. RESULTS: No significant relations
      were found between AUCg, AUCi, evening cortisol and depression severity,
      psychomotor symptoms, and presence of psychosis. In addition, no significant
      relation was found between cortisol and response or remission. CONCLUSIONS: Our
      results do not support a relation between cortisol values and depression
      characteristics, or ECT outcome in severely depressed, older patients treated
      with ECT.

PMID- 29376463
TI  - Could myeloperoxidase represent a useful biomarker for erosive osteoarthritis of
      the hand?

PMID- 29376464
TI  - The flavonoid, 2'-methoxy-6-methylflavone, affords neuroprotection following
      focal cerebral ischaemia.
AB  - Tonic inhibitory currents, mediated by extrasynaptic GABAA receptors, are
      elevated at a delay following stroke. Flavonoids minimise the extent of cellular
      damage following stroke, but little is known about their mode of action. We
      demonstrate that the flavonoid, 2'-methoxy-6-methylflavone (0.1-10 uM; 2'MeO6MF),
      increases GABAA receptor tonic currents presumably via delta-containing GABAA
      receptors. Treatment with 2'MeO6MF 1-6 h post focal ischaemia dose dependently
      decreases infarct volume and improves functional recovery. The effect of 2'MeO6MF
      was attenuated in delta-/- mice, indicating that the effects of the flavonoid
      were mediated via delta-containing GABAA receptors. Further, as flavonoids have
      been shown to have multiple modes of action, we investigated the anti
      inflammatory effects of 2'MeO6MF. Using a macrophage cell line, we show that
      2'MeO6MF can dampen an LPS-induced elevation in NFkB activity. Assessment of
      vehicle-treated stroke animals revealed a significant increase in circulating
      IL1beta, TNFalpha and IFgamma levels. Treatment with 2'MeO6MF dampened the stroke
      induced increase in circulating cytokines, which was blocked in the presence of
      the pan-AKT inhibitor, GSK690693. These studies support the hypothesis that
      compounds that potentiate tonic inhibition via delta-containing GABAA receptors
      soon after stroke can afford neuroprotection.

PMID- 29376465
TI  - Burden of gout in the Nordic region, 1990-2015: findings from the Global Burden
      of Disease Study 2015.
AB  - OBJECTIVE: To explore the burden of gout in the Nordic region, with a population
      around 27 million in 2015 distributed across six countries. METHOD: We used the
      findings of the 2015 Global Burden of Diseases study to report prevalence and
      disability associated with gout in the Nordic region. RESULTS: From 1990 to 2015,
      the number of prevalent gout cases rose by 30% to 252 967 [95% uncertainty
      interval (UI) 223 478-287 288] in the Nordic region. In 2015, gout contributed to
      7982 (95% UI 5431-10 800) years lived with disability (YLDs) in the region, an
      increase of 29% (95% UI 24-35%) from 1990. While the crude YLD rate of gout
      increased by 12.9% (95% UI 7.8-18.1%) between 1990 and 2015, the age-standardized
      YLD rate remained stable. Gout was ranked as the 63rd leading cause of total YLDs
      in the region in 2015, with the highest rank in men aged 55-59 years (38th
      leading cause of YLDs). The corresponding rank at the global level was 94. Of 195
      countries studied, four Nordic countries [Greenland (2nd), Iceland (12th),
      Finland (14th), and Sweden (15th)] were among the top 15 countries with the
      highest age-standardized YLD rate of gout. CONCLUSION: The burden of gout is
      rising in the Nordic region. Gout's contribution to the total burden of diseases
      in the region is more significant than the global average. Expected increases in
      gout burden owing to population growth and ageing call for stronger preventive
      and therapeutic strategies for gout management in Nordic countries.

PMID- 29376466
TI  - Women's leadership in neuropsychology: historical perspectives, present trends,
      and future directions.
AB  - OBJECTIVE: Although psychology has become a female-dominated field, this pattern
      of gender representation has not held true within the specialty of
      neuropsychology. In recent years more women have been pursuing careers in
      neuropsychology, and while the balance of male and female neuropsychologists as a
      whole has shifted, it is unclear whether the gender composition of leadership has
      also changed. Our goal was to survey various neuropsychological organizations,
      training programs, editorial boards, and organizations granting board
      certification to determine the current gender composition of leadership positions
      within neuropsychology. METHOD: A literature review was conducted to examine past
      trends of gender composition in neuropsychology, psychology, medicine, and
      academia. Data on current gender compositions of the field were culled from
      publicly available websites and through personal communication with
      representatives from major psychological and neuropsychological organizations.
      RESULTS: We found that the overall composition of the field has changed over
      time, but notable gender disparities in leadership positions remain. Women still
      comprise the minority of leadership positions within most neuropsychological
      organizations, editorial boards for neuropsychology journals, and fellow
      positions in major neuropsychological organizations. More equitable
      representation has been achieved in the directorships of training programs and
      ABPP/ABCN board certification. CONCLUSION: We review the historical trends in
      gender discrepancies in leadership in neuropsychology and discuss these within
      the broader arenas of academia, research, and medicine. We conclude with a
      summary addressing potential causes for these discrepancies, including work-life
      balance issues, discrimination, institutional bias, and various other factors. We
      also provide pragmatic suggestions to help address these continued disparities.

PMID- 29376468
TI  - Nanomedicines in the treatment of brain tumors.

PMID- 29376467
TI  - Diaphragmatic dysfunction in sepsis due to severe acute pancreatitis complicated
      by intra-abdominal hypertension.
AB  - Objective This study aimed to examine the mechanism of diaphragmatic dysfunction
      in sepsis due to severe acute pancreatitis (SAP) with intra-abdominal
      hypertension (IAH) in a rat model. Methods The rats were assigned at random to
      four groups: (1) control (n = 5), (2) SAP (n = 5), (3) SAP+IAH (n = 5), and (4)
      SAP+IAH+SS-31 (n = 5). Length and force output of the diaphragm were analysed in
      vivo. Histopathological examinations were performed by haematoxylin-eosin.
      Oxidative stress levels related to protease in diaphragmatic mitochondria were
      detected with a colorimetric technique. Results In the septic rat model due to
      SAP complicated by IAH, myofibres were increased. Muscle contractile function was
      significantly lower in the SAP+IAH group compared with the SAP and control
      groups. Glutathione peroxidase and superoxide dismutase levels were significantly
      lower and malondialdehyde levels were higher in the SAP and SAP+IAH groups
      compared with the control group. Notably, SS-31 could reverse atrophy of
      myofibres in SAP+IAH rats, as well as contractile dysfunction and mitochondrial
      dysfunction in the diaphragm. Conclusions Diaphragmatic structure and
      biomechanics are altered in septic rats due to SAP and IAH. This finding is
      mainly due to an increase in release of mitochondrial reactive oxygen species.

PMID- 29376469
TI  - Magnetic iron oxide nanoparticles as drug carriers: clinical relevance.
AB  - Significant preclinical and clinical research has explored the use of magnetic
      iron oxide nanoparticles (MNPs) for medical theranostics. Herein, we provide an
      overview of the optimal 'design-to-perform' MNPs used in cancer therapeutics,
      specifically focusing on magnetic hyperthermia, magnetic drug targeting, and
      targeting delivery. An account of the progress made in the clinic using MNPs is
      then analyzed. We place special emphasis on past and present magnetic
      nanoformulations used in clinical settings or yet to be clinically approved.
      Regrettably, as of now, no MNP drug delivery system is employed in the clinic.
      Thus, identifying current limitations, misconceptions and challenges will
      definitely impact the clinical success of MNP delivery theranostic systems and
      their promising future potential in medicine.

PMID- 29376470
TI  - A case of refractory acute sarcoid myopathy successfully treated with intravenous
      immunoglobulin.

PMID- 29376472
TI  - Community vulnerability and stratified risk: Hegemonic masculinity, socioeconomic
      status, and HIV/AIDS in a sex work community in Kampala, Uganda.
AB  - This article examines the social patterning of health, economic uncertainty,
      hegemonic masculinity, and vulnerability among men who live and work in a low
      income sex work community in Kampala, Uganda. This problematises the notion that
      vulnerable communities are homogenous, in demographics, economic status, and
      risk. This article draws on ethnographic data collected in 2016, including semi
      structured interviews and participant observation. This article uses a stratified
      risk framework to describe the central finding of this study, which is that men's
      experience in Kataba is characterised by a struggle to fulfil the provider role
      that constitutes a core aspect of their socially ascribed gender role. In a
      context of economic scarcity, men's lives are fraught with strain and this
      intersects with other forms of risk. Finally, by focusing on community
      vulnerability rather than individual risk, this work contributes to theories of
      gender and sex work, and informs HIV/AIDS praxis.

PMID- 29376471
TI  - Emerging roles of SGLT2 inhibitors in obesity and insulin resistance: Focus on
      fat browning and macrophage polarization.
AB  - Obesity-associated low-grade inflammation underlies insulin resistance and
      associated metabolic comorbidities, such as type 2 diabetes (T2D) and
      nonalcoholic fatty liver disease. Excessive ectopic fat deposition in obesity
      causes disorders of energy homeostasis and low-grade chronic inflammation in
      metabolic tissues. In particular, obesity-induced recruitment and activation of
      adipose tissue macrophages play a key role in the pathogenesis of insulin
      resistance and T2D. Therefore, treatment options for energy metabolism and
      macrophage polarization in obese subjects are needed. Sodium-glucose
      cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion by
      inhibiting renal glucose reabsorption, thereby having subsequent anti
      hyperglycemic effects and reducing body weight. We recently reported that the
      SGLT2 inhibitor empagliflozin increases fat utilization and browning in white
      adipose tissue and attenuates obesity-induced inflammation and insulin resistance
      by activating M2 macrophages. Thus, this review focuses on the beneficial effects
      of empagliflozin in energy homeostasis and obesity-related inflammation and
      insulin resistance.

PMID- 29376473
TI  - It is all about the support - The role of the extracellular matrix in
      regenerating axon guidance.
AB  - Although it is known for long time that the peripheral nervous system has the
      capacity for self-regeneration, the molecular mechanisms by which Schwann cells
      and extracellular matrix (ECM) guide the injured axons to regrow along their
      original path, remains a poorly understood process. Due to the importance of ECM
      molecules during development, constitutive mutant organisms display increased
      lethality, therefore, conditional or inducible strategies have been used to
      increase the survival of the organisms and allow the study of the role of ECM
      proteins. In a recent report published in Neuron, Isaacman-Beck and colleagues
      (2015) used these pioneering genetic studies on zebrafish combined with in vivo
      fluorescent imaging, to investigate the micro-environmental conditions required
      for targeted regeneration of the dorsal motor nerve of zebrafish larvae after
      laser-transection. A candidate gene approach targeting lh3 basal laminar collagen
      substrates revealed that the lh3 substrate col4alpha5 regulates dorsal nerve
      regeneration by destabilizing misdirected axons. Col4alpha5 was upregulated in a
      small population of lh3 expressing Schwann cells located ventrally and ventro
      laterally to the injury site and found to co-localize with the molecule slit
      guidance ligand 1 (slit1a). Capitalizing on the crucial observations of
      mistargeted regeneration of dorsal nerves in mutant larvae, they put forward a
      model in which Schwann cells shape an environment that allows and directs axonal
      regeneration to their original synaptic target. In the light of Isaacman-Beck and
      colleagues (2015) findings, we will review how their study contributes to the
      research field, and comment on its potential implications for promoting nerve
      regeneration after injury.

PMID- 29376474
TI  - Relationship between plasma trans-fatty acid isomer concentrations and self
      reported cardiovascular disease risk in US adults.
AB  - The effect of different individual TFA isomers on cardiovascular disease (CVD)
      has been a limited study, especially for stroke. We aimed to investigate the
      relationships between four major plasma TFA isomer (elaidic, vaccenic,
      palmitelaidic and linolelaidic acid) concentrations and the risk of CVD, stroke
      and non-stroke CVD. A cross-sectional study was conducted, utilising a nationally
      representative sample of US adults in the National Health and Nutrition
      Examination Survey. Among the 3504 participants, 304 participants self-reported
      CVD history. The highest quintile of elaidic acid intake was associated with a
      233% higher CVD risk (p = .010). Adjusted for age, gender and race, palmitelaidic
      acid was associated with a decreased CVD risk, but the effect size was diminished
      in a subsequent analysis model. For stroke risk, we failed to identify any
      associations. In addition to elaidic acid, the health effect of palmitelaidic
      acid should be paid more attention in the future studies.

PMID- 29376475
TI  - Non-melanoma skin cancer as a possible adverse event due to anti-interleukin-6
      treatment.

PMID- 29376477
TI  - Improved Osteogenesis by HVEM-Expressing Allogenic Bone Marrow-Derived
      Mesenchymal Stem Cells in an Immune Activation Condition and Mouse Femoral Defect
      Model.
AB  - Use of allogeneic mesenchymal stem cells (allo-MSCs) in bone tissue engineering
      strategies can overcome the limitations associated with autologous MSCs, but
      unfortunately, the immunogenicity of allo-MSCs leads to a high rate of rejection,
      unless immunosuppressive agents are used. B and T lymphocyte attenuator (BTLA) is
      a newly discovered immunoglobulin superfamily inhibitory receptor, and
      Herpesvirus-entry mediator (HVEM), a member of the tumor necrosis factor receptor
      family, is the only ligand of BTLA. Both BTLA and HVEM are widely expressed in B
      and T lymphocytes and other immune cells and play significant roles in the
      negative regulation of an immunoreaction. Therefore, we hypothesized that MSCs
      could be modified to maintain their bone differentiation ability through negative
      regulation of the immune response, and to test this hypothesis, we generated HVEM
      expressing MSCs and tested their potential for osteogenic differentiation and
      bone repair in a simulated immune activation condition in vitro and in a mice
      femoral defect model. We found that osteogenic differentiation of allo-MSCs was
      decreased significantly in the activated immune microenvironment and that HVEM
      expression by allo-MSCs inhibited the immune response, resulting in improved
      osteogenic differentiation in vitro and new bone formation by allo-MSCs in a
      mouse femoral defect model. Our results also preliminarily suggested that the
      mechanism by which HVEM-expressing allo-MSCs overcome inflammation and enhance
      osteogenesis may be related to inhibition of interleukin-17. Overall, the data
      obtained in the present study provide support for the further development of HVEM
      modified allo-MSCs as potentially ideal seed cells for bone tissue engineering
      applications.

PMID- 29376478
TI  - Relationship of self-reported sleep bruxism and awake bruxism with chronotype
      profiles in Italian dental students.
AB  - OBJECTIVES: A cross-sectional study was performed to assess the association
      between possible sleep bruxism (SB) and awake bruxism (AB) with sleep
      characteristics and chronotype (i.e. circadian cycle preference). METHODS: One
      hundred-nineteen young adults filled out a self-reported questionnaire to assess
      SB and AB, a questionnaire about daily life aspects, as well as the Morningness
      Eveningness Questionnaire (MEQ) to profile chronotype. RESULTS: The frequency of
      self-reported SB and AB was 25.2% and 37.0%, respectively. Both SB and AB were
      significantly more frequent in females than males. Most participants had an
      intermediate chronotype profile (n = 85; 71.4%). Neither SB (p = 0.556) nor AB (p
      = 0.334) were associated with chronotype. Nightmares were more prevalent among
      individuals with possible SB (38.3%). Difficulty concentrating in daily
      activities was more frequently reported among individuals with AB (51.9%).
      CONCLUSION: There was no association between possible SB and AB or the chronotype
      profiles among Italian dental students.

PMID- 29376479
TI  - Tooth loss and craniofacial factors associated with changes in mandibular
      condylar morphology.
AB  - OBJECTIVE: To investigate the association between tooth loss and craniofacial
      factors with changes in mandibular condylar morphology. METHODS: A total of 123
      patients participated in this cross-sectional study. The mandibular condylar
      morphology was evaluated using digital panoramic radiography. The exposure
      variables included gender, age group, molar relationship, facial growth pattern,
      facial asymmetry, dental midline, posterior crossbite, presence of fixed dental
      prosthesis, and tooth loss. RESULTS: Unilateral and bilateral mandibular condyle
      structural alterations were found in 20.3% and 28.5% of the sample, respectively.
      After the adjustment analysis, posterior crossbite (adjusted OR = 3.34, 95% CI =
      1.23-9.06) and tooth loss (adjusted OR = 4.08, 95% CI = 1.72-9.64) were
      associated with the outcome. The tooth type associated with mandibular condyle
      structural alterations were premolars and upper molars. CONCLUSION: The findings
      suggest that posterior crossbite and tooth loss are associated with mandibular
      condyle structural alterations.

PMID- 29376476
TI  - A bite to fight: front-line innate immune defenses against malaria parasites.
AB  - Malaria infection caused by Plasmodium parasites remains a major health burden
      worldwide especially in the tropics and subtropics. Plasmodium exhibits a complex
      life cycle whereby it undergoes a series of developmental stages in the Anopheles
      mosquito vector and the vertebrate human host. Malaria severity is mainly
      attributed to the genetic complexity of the parasite which is reflected in the
      sophisticated mechanisms of invasion and evasion that allow it to overcome the
      immune responses of both its invertebrate and vertebrate hosts. In this review,
      we aim to provide an updated, clear and concise summary of the literature
      focusing on the interactions of the vertebrate innate immune system with
      Plasmodium parasites, namely sporozoites, merozoites, and trophozoites. The roles
      of innate immune factors, both humoral and cellular, in anti-Plasmodium defense
      are described with particular emphasis on the contribution of key innate players
      including neutrophils, macrophages, and natural killer cells to the clearance of
      liver and blood stage parasites. A comprehensive understanding of the innate
      immune responses to malaria parasites remains an important goal that would
      dramatically help improve the design of original treatment strategies and
      vaccines, both of which are urgently needed to relieve the burden of malaria
      especially in endemic countries.

PMID- 29376480
TI  - Fluorination Enhances the Osteogenic Capacity of Porcine Hydroxyapatite.
AB  - In a previous study, we successfully prepared fluorinated porcine hydroxyapatite
      (FPHA) by immersing porcine hydroxyapatite (PHA) in an aqueous solution of 0.25 M
      sodium fluoride (NaF) under thermal treatment, and the resulting FPHA showed
      better physicochemical and biological properties than PHA. The purpose of this
      study was to further investigate how fluorine incorporation influenced the
      biocompatibility and osteogenic capacity of PHA. The concentrations of Ca, P, F,
      and Mg ions in PHA and FPHA extracts were detected by inductively coupled plasma
      optical emission spectrometry. Rat bone marrow stromal cells (rBMSCs) were
      treated with PHA and FPHA extracts, and the effects of these extracts on cell
      proliferation and osteoblastic differentiation were evaluated via Cell Counting
      Kit-8 assay, alkaline phosphatase assay, and real time-quantitative polymerase
      chain reaction. For the in vivo assessment, PHA and FPHA were implanted into
      subcutaneous pockets (n = 6) and rat calvarial defects (diameter = 5 mm, n = 14)
      for 12 weeks to determine their biocompatibility and osteogenic capacity by using
      micro-computed tomography (CT) and histological analysis. FPHA extracts, which
      release higher concentrations of F and Mg ions, better promoted the osteoblastic
      differentiation of rBMSCs in vitro. The result of biocompatibility evaluation
      confirmed that the host response and chronic inflammation cells infiltration
      degree around PHA and FPHA granules were similar. Micro-CT and histological
      analysis showed newer mineralized bone formation in rats with FPHA-treated
      defects than in rats with PHA-treated defects. The results of in vitro and in
      vivo tests consistently indicate that fluorine incorporation effectively enhanced
      the osteogenic capacity of PHA.

PMID- 29376481
TI  - Dyspareunia is associated with chronic pain in premenopausal women with sickle
      cell disease.
AB  - OBJECTIVES: Pain is common in women with sickle cell disease (SCD), but the
      prevalence of dyspareunia in this unique patient population is unknown. In this
      study, we sought to determine whether chronic pain is associated with an
      increased prevalence of dyspareunia in premenopausal women with SCD. METHODS: A
      cross-sectional study of premenopausal women with SCD was systematically assessed
      for symptoms of dyspareunia and chronic pain using a standard questionnaire.
      These results were correlated with each subject's clinical pain phenotype
      determined by a review of the patient's electronic medical record. RESULTS:
      Ninety-one premenopausal women with SCD were examined. Thirty-two percent of the
      women reported dyspareunia. Women with dyspareunia were more likely to have a
      history of chronic pain (90% versus 61%, p = .006), report more pain days per
      week (median (interquartile range): 6 (4-7) vs. 3 (0-7), p = .005)), and had a
      higher oral morphine equivalent dose (145 (45-226) mg vs. 60 (9-160) mg, p =
      .030). Using a multivariable classification tree analysis, number of days of pain
      experienced per week was an important predictor of dyspareunia (p = .001).
      CONCLUSION: Dyspareunia is common in women with SCD, and more common in women
      with SCD and chronic pain. Providers should assess women with SCD for
      dyspareunia, especially those with a chronic pain syndrome.

PMID- 29376482
TI  - Effects of orthopedic insoles on static balance of older adults wearing thick
      socks.
AB  - BACKGROUND: The wearing of socks and insoles may affect the ability of the foot
      to detect tactile input influencing postural balance. OBJECTIVES: The aim of this
      study was to investigate whether (1) thick socks adversely affected the elderly
      postural balance and (2) orthopedic insoles could improve the elderly postural
      balance while wearing thick socks. STUDY DESIGN: Repeated-measures study design.
      METHODS: In total, 14 healthy older adults were recruited. A monofilament test
      was conducted to evaluate foot plantar sensation with and without thick socks.
      Subjects then performed the Romberg tests under three conditions: (1) barefoot,
      (2) with socks only, and (3) with both socks and insoles. Postural balance was
      assessed by measuring the center of pressure movement during standing in each
      experimental condition. RESULTS: Thick socks significantly decreased the
      monofilament score ( p < 0.001), suggesting reduction in ability to detect
      external forces. All center of pressure parameters increased significantly while
      wearing thick socks ( p < 0.017), implying reduction of postural stability. They
      then decreased significantly with the additional use of insoles ( p < 0.017).
      CONCLUSION: Previous studies have documented the changes in plantar pressure
      distribution with the use of orthopedic insoles. This study further suggests that
      such changes in contact mechanics could produce some balance-improving effects,
      which appears not to have been reported earlier. Clinical relevance Wearing thick
      socks reduces plantar pressure sensitivity and increases postural sway which may
      increase risk of falls. Orthopedic insoles and footwear with similar design could
      potentially be a cost-effective method in maintaining postural balance when
      wearing thick socks.

PMID- 29376483
TI  - Gold Nanoparticle-Collagen Gels for Soft Tissue Augmentation.
AB  - Collagen soft tissue fillers suffer from fast reabsorption, which minimizes their
      use as a tissue-engineered construct. Extensive cross-linking can be utilized to
      extend longevity, but changes in microstructure and biomechanics can have
      deleterious effects. To enhance longevity while still achieving a natural
      microstructure, gold nanoparticles (AuNPs) were conjugated to fibrilized collagen
      and homogenized into an injectable form for use as a soft tissue filler. A long
      term animal study in Yucatan swine was conducted to assess biocompatibility and
      longevity. Two formulations of the AuNP-collagen were compared to porcine cross
      linked collagen and commercially available hyaluronic acid (HA). The results of
      the study demonstrated that the AuNPs may provide enhanced longevity over 6
      months compared to HA and cross-linked collagen. Irritation scores indicated that
      the AuNP-collagen construct (AuNP-CC) demonstrated low irritation compared to the
      cross-linked collagen and HA while histology scores demonstrated good
      biocompatibility. Overall, it may be possible to utilize AuNPs to stabilize and
      increase the longevity of CC while still achieving biocompatibility.

PMID- 29376484
TI  - Studies on the preparation and controlled release of redox/pH-responsive
      zwitterionic nanoparticles based on poly-L-glutamic acid and cystamine.
AB  - The enhancement of tumor intracellular drug uptake and resistance against
      nonspecific protein adsorption are essential for an injectable anticancer drug
      carrier. In the present study, a new type of redox/pH-responsive zwitterionic
      nanoparticles (NPs) was prepared using poly-L-glutamic acid and cystamine in
      aqueous solutions under mild conditions. The NPs showed surface charge
      convertible feature in response to pH change of the solutions. The NPs
      demonstrated excellent anti nonspecific protein adsorption. In vitro release
      profiles of the NPs, they showed redox/pH dual sensitivities in vitro release.
      The effective intracellular delivery behaviors were verified through
      investigation of cell viability, and confocal laser scanning microscopy
      observation of HeLa cells after incubation with the DOX-loaded NPs. The NPs were
      non-cytotoxic and would have potential applications as a drug delivery vehicle
      for enhancing intracellular uptake of anticancer drugs.

PMID- 29376486
TI  - The Mental Capacity Act 2005 best interests test as applied to the elderly - is
      it fit for purpose?
AB  - The Mental Capacity Act 2005 ('MCA') sets out a regime which governs the making
      of decisions for people who lack mental capacity. Acts must be carried out, and
      decisions made, for such an incapacitated person, based on what is in her best
      interests (section 4 MCA). In this paper, I consider the body of post-MCA case
      law which applies the MCA best interests test to decision-making for elderly
      people, in various contexts. Is the best interests test 'fit for purpose' for the
      vulnerable elderly? The key aims of Parliament in introducing the test seem to
      have been empowerment, protection and support - and alertness to undue influence 
      as well as a balance between the objective and subjective viewpoints. Laudable
      attempts have been made by some judges, applying the MCA, to pay real heed to the
      patient's wishes and values, and to balance physical risk with welfare and
      happiness. However, it is not yet clear in my view that the new regime fully
      achieves Parliament's aims. Indeed, these aims themselves should be expanded; the
      law in this area should also promote the significance and value of advanced years
      and should recognise Aristotle's concept of 'human flourishing' in old age.
      Consideration should be given to amending the MCA, adding guidance specifically
      for the elderly and also to introducing a Convention of Human Rights for the
      older person and to creating a new statutory Older Persons' Commissioner and/or a
      cabinet-level Minister for Ageing and Older People.

PMID- 29376485
TI  - Genome-wide oxidative bisulfite sequencing identifies sex-specific methylation
      differences in the human placenta.
AB  - DNA methylation is an important regulator of gene function. Fetal sex is
      associated with the risk of several specific pregnancy complications related to
      placental function. However, the association between fetal sex and placental DNA
      methylation remains poorly understood. We carried out whole-genome oxidative
      bisulfite sequencing in the placentas of two healthy female and two healthy male
      pregnancies generating an average genome depth of coverage of 25x. Most highly
      ranked differentially methylated regions (DMRs) were located on the X chromosome
      but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi
      Multiple Domains 1 (CSMD1) gene on chromosome 8. The sex-specific differential
      methylation pattern observed in this region was validated in additional placentas
      using in-solution target capture. In a new RNA-seq data set from 64 female and 67
      male placentas, CSMD1 mRNA was 1.8-fold higher in male than in female placentas
      (P value = 8.5 * 10-7, Mann-Whitney test). Exon-level quantification of CSMD1
      mRNA from these 131 placentas suggested a likely placenta-specific CSMD1 isoform
      not detected in the 21 somatic tissues analyzed. We show that the gene body of an
      autosomal gene, CSMD1, is differentially methylated in a sex- and placental
      specific manner, displaying sex-specific differences in placental transcript
      abundance.

PMID- 29376487
TI  - Surfing the Blood Coagulation Cascade: Insight into the Vital Factor Xa.
AB  - Factor Xa (FXa) plays a key role in haemostasis, it is a central part of the
      blood coagulation cascade which catalyzes the production of thrombin and leads to
      clot formation and wound closure. Therefore, FXa is an attractive target for the
      development of new anticoagulant agents. In this review, we will first describe
      the molecular features of this fundamental protein in order to understand its
      mechanism of action, an essential background for the design of novel inhibitors
      by means of synthetic organic chemistry or using peptides obtained from
      recombinant methodologies. Then, we will review the current state of the
      synthesis of novel direct FXa inhibitors along with their mechanisms of action.
      Finally, approved reversal agents that aid in maintaining blood haemostasis by
      using these commercial drugs will be also discussed.

PMID- 29376488
TI  - Analytical and Preparative Scale Separation of Enantiomers of Chiral Drugs by
      Chromatography and Related Methods.
AB  - While the amino acids, enzymes and hormones are chiral, chirality plays
      significant role in the life of plants, animals, as well as the human being.
      Chirality of molecules is important in various industries, such as
      pharmaceutical, agricultural, food, electronics, etc. Chiral drugs may have
      different bioavailability, distribution, biotransformation and excretion, as well
      as quantitatively and/or qualitatively different pharmacological or toxic
      properties. Enantiomerically pure chiral drugs have been increasingly developed
      for the pharmaceutical market due to their superiority from the viewpoints of
      potency and safety. This is supported by the development of new methods for
      enantioselective production of the chiral compounds, as well as by the capability
      of the enantioselective analytical methods to allow a detection and
      quantification of minor enantiomeric impurity in the presence of another
      enantiomer in a large excess. The aim of the present review is to provide a short
      summary of the basic principles of chiral separations on an analytical and
      preparative scale. In addition, some selected applications for analytical
      techniques, such as gas chromatography, supercritical fluid chromatography, high
      performance liquid chromatography, capillary electrophoresis and capillary
      electrochromatography for the separation of enantiomers of chiral pharmaceuticals
      published in the last two years are also discussed.

PMID- 29376489
TI  - Advances in the Development of Anticancer HSP-based Vaccines.
AB  - Current advances in cancer treatment are based on the recent discoveries of
      molecular mechanisms of tumour maintenance. It was shown that heat shock proteins
      (HSPs) play a crucial role in the development of the immune response against
      tumours. Thus, HSPs represents multifunctional agents not only with chaperone
      functions, but that also possess immunomodulatory properties. These properties
      are exploited for the development of HSP-based anticancer vaccines aimed to
      induce cytotoxic responses against tumours. To date a number of strategies have
      been suggested to facilitate HSP-based vaccine production and to increase its
      effectiveness. The present review focuses on the current trend for the
      development of HSP-based vaccines aimed at inducing strong immunological tumour
      specific responses against cancer cells of distinct etiology and localization.

PMID- 29376490
TI  - Targeting DNA repair systems in antitubercular drug development.
AB  - Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis,
      are difficult to treat using currently available chemotherapeutics. Clinicians
      agree on the urgent need for novel drugs to treat tuberculosis. In this mini
      review, we summarize data that prompts the consideration of DNA repair-associated
      proteins as targets for the development of new antitubercular compounds. We
      discuss data, including gene expression data, that highlight the importance of
      DNA repair genes during the pathogenic cycle as well as after exposure to
      antimicrobials currently in use. Specifically, we report experiments on
      determining the essentiality of DNA repair-related genes. We report the
      availability of protein crystal structures and summarize discovered protein
      inhibitors. Further, we describe phenotypes of available gene mutants of M.
      tuberculosis and model organisms Mycobacterium bovis and Mycobacterium smegmatis.
      We summarize experiments regarding the role of DNA repair-related proteins in
      pathogenesis and virulence performed both in vitro and in vivo during the
      infection of macrophages and animals. We detail the role of DNA repair genes in
      acquiring mutations, which influence the rate of drug resistance acquisition.

PMID- 29376491
TI  - Ganglioside GM3 and Its Role in Cancer.
AB  - Ganglioside GM3 is strongly related with human tumors, such as lung, brain
      cancers and melanomas, and more and more evidences have revealed that GM3
      possesses powerful effects on cancer development and progression. GM3 is over
      expressed on several types of cancers, and can be as a tumor-associated
      carbohydrate antigen, used for immunotherapy of cancers. GM3 can also inhibit
      tumor cells growth by anti-angiogenesis or motility and so on. Especially, GM3
      has effects on the EGFR tyrosine kinase signaling, uPAR-related signaling and
      glycolipid-enriched microdomains, which are essential for cancer signaling
      conduction. It is obvious that GM3 will be a promising target for cancer
      treatment.

PMID- 29376492
TI  - Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer's Disease?
      Molecular Mechanisms and Clinical Implications.
AB  - Proton-pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole,
      are used for the treatment of gastroesophageal reflux disease and peptic ulcer
      disease. The use of PPIs has increased, especially in older individuals, and a
      pharmacoepidemiological study indicated the use of PPIs peaks in people aged 80
      years or older. In this population, Alzheimer's disease (AD) is a common
      neurological disorder and type of dementia, occurring with a frequency of
      approximately 10%. Currently, over 45 million people are estimated to have
      dementia worldwide, and it is a major cause of death in the elderly. Recent
      clinical studies have indicated that chronic use of PPIs can be a risk factor for
      increased incidence of dementia, including AD. Potential molecular mechanisms
      related to the pathophysiology of AD (e.g., modulation of amyloid protein
      processing) have also been reported in both in vitro and in vivo studies.
      Although the clinical implications of these results are inconclusive, a
      literature review of the current knowledge is important for future basic and
      clinical research. This review summarizes the possible mechanisms connecting the
      use of PPIs and the incidence of AD. Additionally, we summarize results from
      clinical studies to highlight the influence in humans.

PMID- 29376493
TI  - Placental Exosomes During Gestation: Liquid Biopsies Carrying Signals for the
      Regulation of Human Parturition.
AB  - Parturition is defined as the action or process of giving birth to offspring.
      Normal term human parturition ensues following the maturation of fetal organ
      systems typically between 37 and 40 weeks of gestation. Our conventional
      understanding of how parturition initiation is signaled revolves around feto
      maternal immune and endocrine changes occurring in the intrauterine cavity. These
      changes in turn correlate with the sequence of fetal growth and development.
      These important physiological changes also result in homeostatic imbalances which
      result in heightened inflammatory signaling. This disrupts the maintenance of
      pregnancy, thus leading to laborrelated changes. However, the precise mechanisms
      of the signaling cascades that lead to the initiation of parturition remain
      unclear, although exosomes may be a mediator of this process. Exosomes are a
      subtype of extracellular vesicles characterised by their endocytic origin. This
      involves the trafficking of intraluminal vesicles into multivesicular bodies
      (MVB) and then exocytosis via the plasmatic membranes. Exosomes are highly stable
      nanovesicles that are released by a wide range of cells and organs including the
      human placenta and fetal membranes. Interestingly, exosomes from placental origin
      have been uncovered in maternal circulation across gestation. In addition, their
      concentration is higher in pregnancies with complications such as gestational
      diabetes and preeclampsia. In normal gestation, the concentration of placental
      exosomes in maternal circulation correlates with placental weight at third
      trimester. The role of placental exosomes across gestation has not been fully
      elucidated, although recent studies suggest that placental exosomes are involved
      in maternal-fetal inmmuno-tolerance, maternal systemic inflammation and nutrient
      transport. The content of exosomes is of particular importance, encompassing a
      large range of molecules such as mRNA, miRNAs, DNA, lipids, cell-surface
      receptors, and protein mediators. These can in turn interact with either adjacent
      or distal cells to reprogram their phenotype and regulate their function. Many of
      the pro-parturition proinflammatory mediators reach maternal compartments from
      the fetal side via circulation, but major impediments remain, such as degradation
      at various levels and limited halflife in circulation. Recent findings suggest
      that a more effective mode of communication and signal transport is through
      exosomes, where signals are protected and will not succumb to degradation. Thus,
      understanding how exosomes regulate key events throughout pregnancy and
      parturition will provide an opportunity to understand the mechanisms involved in
      the maternal and fetal metabolic adaptations during normal and pathological
      pregnancies. Subsequently, this will assist in identifying those pregnancies at
      risk of developing complications. This may also allow more appropriate
      modifications of their clinical management. This review will hence examine the
      current body of data to summarise our understanding of how signaling pathways
      lead to the beginning of parturition. In addition, we propose that extracellular
      vesicles, namely exosomes, may be an integral component of these signaling events
      by transporting specific signals to prepare the maternal physiology to initiate
      parturition. Understanding these signals and their mechanisms in normal term
      pregnancies can provide insight into pathological activation of these signals,
      which can cause spontaneous preterm parturition. Hence, this review expands on
      our knowledge of exosomes as professional carriers of fetal signals to instigate
      human parturition.

PMID- 29376494
TI  - Antiarthritic Effect of Polar Extract of Curcuma longa on Monosodium Iodoacetate
      Induced Osteoarthritis in Rats.
AB  - BACKGROUND: Curcuma longa Linn, "the golden spice" is a common spice used in
      Southern Asia and Middle East countries. It has a history of ethnopharmacological
      use for its various activities like anti-septic, anti-inflammatory, anti-oxidant,
      anti-microbial, anti-cancer and so on. OBJECTIVE: To investigate the effects of
      polar extract of C. longa (PCL) against monosodium iodoacetate (MIA) induced
      osteoarthritis in rat and to compare with curcuminoids, which are contemporarily
      believed to be the only active phytochemicals of C. longa for relieving pain in
      osteoarthritis. METHOD: Osteoarthritis in rats was induced by intra-articular
      injection of monosodium iodoacetate (MIA) in right knee. PCL or curcuminoids or
      tramadol was administered orally as single dose on the 5th day post MIA injection
      to rats. Weight bearing capacity and percentage inhibition of nociception of PCL
      treated groups were determined and compared with curcuminoids and tramadol
      (reference drug). In addition, gene expression levels of type II collagen and
      matrix metalloproteinases (MMP) in joint cartilage was measured by Reverse
      transcription polymerase chain reaction. RESULTS: PCL significantly decreased the
      difference in weight distribution between left and right limb in a dose dependent
      manner. Anti-arthritic activity of PCL is evident from significant up regulation
      of type II collagen gene (COL2A1) and down regulation of MMP-3 and MMP-7.
      CONCLUSION: Polar extract of C. longa showed beneficial effects on joints by
      exhibiting antiosteoarthritic effects via maintaining equilibrium between
      anabolic and catabolic factors of joint cartilage.

PMID- 29376495
TI  - Therapeutic Potential of N-heterocyclic Analogs as Anti-inflammatory Agents.
AB  - BACKGROUND: Various mediators and anti-inflammatory drugs were used since from a
      long time but it is still a challenge for the medicinal chemists to treat or
      reduce the symptoms of inflammatory diseases. Most of the clinically used anti
      inflammatory drugs such as NSAIDs, Coxibs and GCs are allied with considerable
      toxicity. OBJECTIVE: The search of novel anti-inflammatory agent is not an ending
      process. Although the drug treatment has been improved steadily but yet, it is
      still there is a need to develop more potent therapeutic agents. METHOD: Reported
      literature survey has been studied to summarize the nitrogen containing moieties
      which were utilized as potential therapeutic agents. RESULTS: A variety of N
      heterocyclic analogs are known to exhibit a wide range of interesting biological
      activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic,
      antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic,
      antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular,
      trypanocidal and anti-HIV. However, numerous approaches were used to overcome the
      toxicity level such as co-administration with suitable agent/substance which
      provides protection against toxicity as well to synthesise new potent and safe
      anti-inflammatory drug. CONCLUSION: The present review summarizes the synthetic
      methodology and therapeutic potential of some N-heterocyclic analogs as potent
      anti-inflammatory agents.

PMID- 29376497
TI  - L-Sulforaphane Confers Protection Against Oxidative Stress in an In Vitro Model
      of Age-Related Macular Degeneration.
AB  - BACKGROUND: In age-related macular degeneration, oxidative damage and abnormal
      neovascularization in the retina are caused by the upregulation of vascular
      endothelium growth factor and reduced expression of Glutathione-S-transferase
      genes. Current treatments are only palliative. Compounds from cruciferous
      vegetables (e.g. L-Sulforaphane) have been found to restore normal gene
      expression levels in diseases including cancer via the activity of histone
      deacetylases and DNA methyltransferases, thus retarding disease progression.
      OBJECTIVE: To examine L-Sulforaphane as a potential treatment to ameliorate
      aberrant levels of gene expression and metabolites observed in age-related
      macular degeneration. METHOD: The in vitro oxidative stress model of AMD was
      based on the exposure of Adult Retinal Pigment Epithelium-19 cell line to 200MUM
      hydrogen peroxide. The effects of L-Sulforaphane on cell proliferation were
      determined by MTS assay. The role of GSTM1, VEGFA, DNMT1 and HDAC6 genes in
      modulating these effects was investigated using quantitative real-time polymerase
      chain reaction. The metabolic profiling of L-Sulforaphane-treated cells via gas
      chromatography massspectrometry was established. Significant differences between
      control and treatment groups were validated using one-way ANOVA, student t-test
      and post-hoc Bonferroni statistical tests (p<0.05). RESULTS: L-Sulforaphane
      induced a dose-dependent increase in cell proliferation in the presence of
      hydrogen peroxide by upregulating Glutathione-S-Transferase MU1 gene expression.
      Metabolic profiling revealed that L-Sulforaphane increased levels of 2
      monopalmitoglycerol, 9, 12, 15,-(Z-Z-Z)- Octadecatrienoic acid, 2
      [Bis(trimethylsilyl)amino]ethyl bis(trimethylsilyl)-phosphate and nonanoic acid
      but decreased beta-alanine levels in the absence or presence of hydrogen
      peroxide, respectively. CONCLUSION: This study supports the use of L-Sulforaphane
      to promote regeneration of retinal cells under oxidative stress conditions.

PMID- 29376499
TI  - Reply to Comment on 'On the correct use of stepped-sine excitations for the
      measurement and identification of time-varying bioimpedance'.
AB  - OBJECTIVE: The authors Lang and Zalka commented on our previous note (Louarroudi
      and Sanchez 2017 Physiol. Meas. 38 N73-80), indicating interpolation as a
      suitable method to estimate the instantaneous impedance of a time-varying
      impedance from stepped-sine excitations. APPROACH: Here, we briefly delve into
      the underlying assumptions of the interpolation scheme. MAIN RESULTS: We
      illustrate the approximation of the instantaneous impedance of a time-varying
      impedance from stepped-sine measurements conducting experiments on a phantom.
      SIGNIFICANCE: We outline the technical challenges awaiting future research
      required to validate the accuracy of the instantaneous impedance approximation of
      a time-varying impedance using stepped-sine excitations.

PMID- 29376496
TI  - Shift from Levothyroxine Tablets to Liquid Formulation at Breakfast Improves
      Quality of Life of Hypothyroid Patients.
AB  - BACKGROUND: Until recently, treatment of hypothyroidism has been accomplished
      using monotherapy of synthetic L-thyroxine (L-T4) sodium tablets that should be
      taken 30-60 minutes before breakfast. Nowadays, a liquid preparation of
      levothyroxine is available and can effectively replace tablets without the need
      of waiting before having breakfast. Evidence of Quality of life (QoL) improvement
      when shifting from the former to the latter preparation, however, is still
      lacking. OBJECTIVE: The study aimed to assess changes in QoL of hypothyroid
      patients dissatisfied with their therapy with L-T4 sodium tablets who were
      switched from tablets taken 30-60 minutes before breakfast to liquid L-T4 at
      breakfast. METHODS: A total of 418 consecutive hypothyroid subjects treated by
      means of L-T4 tablets were asked about their satisfaction/dissatisfaction in
      order to take the medication 30-60 minutes before having breakfast. Overall, 110
      patients (26.3%) complained of the timing of their L-T4 therapy (30-60 minutes
      before breakfast). A dedicated QoL questionnaire (ThyTSQ), taking just a few
      minutes to be filled in was then administered to these dissatisfied patients.
      They were therefore switched to L-T4 to be taken at breakfast. Aiming to avoid
      TSH elevation due to L-T4 tablets malabsorption caused by meal interference and
      gastric pH changes, patients were invited to take L-T4 liquid form, as this is
      claimed to be scarcely affected by the non-fasting state. The questionnaire
      (ThyTSQ) was administered again at the control visit 3 months later. TSH, FT4,
      FT3 serum concentrations and metabolic parameters were also recorded. RESULTS: An
      improved QoL, mainly due to an easier adherence to treatment, was reported by
      66.6% of 102 patients who completed the study after shifting from taking
      medication 30-60 minutes before breakfast to at breakfast ingestion (P<0.01). An
      overall 10.7% of patients found the liquid formulation distasteful. Mean values
      of TSH, FT4, FT3, and of metabolic parameters did not significantly change but in
      eight patients (7.7%) who showed a TSH increase > 2mIU/L. CONCLUSION: In
      hypothyroid subjects dissatisfied with L-T4 tablets ingested 30-60 minutes before
      breakfast, the shift to the same dose of L-T4 in liquid form taken at breakfast
      improved QoL in the majority of patients, without affecting thyroid function.

PMID- 29376500
TI  - Nanoscale imaging of photocurrent enhancement by resonator array photovoltaic
      coatings.
AB  - Nanoscale surface patterning commonly used to increase absorption of solar cells
      can adversely impact the open-circuit voltage due to increased surface area and
      recombination. Here, we demonstrate absorptivity and photocurrent enhancement
      using silicon dioxide (SiO2) nanosphere arrays on a gallium arsenide (GaAs) solar
      cell that do not require direct surface patterning. Due to the combined effects
      of thin-film interference and whispering gallery-like resonances within
      nanosphere arrays, there is more than 20% enhancement in both absorptivity and
      photocurrent. To determine the effect of the resonance coupling between
      nanospheres, we perform a scanning photocurrent microscopy based on a near-field
      scanning optical microscopy measurement and find a substantial local photocurrent
      enhancement. The nanosphere-based antireflection coating (ARC), made by the Meyer
      rod rolling technique, is a scalable and a room-temperature process; and, can
      replace the conventional thin-film-based ARCs requiring expensive high
      temperature vacuum deposition.

PMID- 29376501
TI  - Cytotoxicity and biocompatibility of biomaterials based in polyhydroxybutyrate
      reinforced with cellulose nanowhiskers determined in human peripheral leukocytes.
AB  - Implants of materials that are typically considered inert have been shown to
      cause early inflammatory complications. In addition, implant wear products may
      also cause overproduction of proinflammatory cytokines in the long run. Among the
      cytokines is tumor necrosis factor alpha (TNFalpha), which not only participates
      in the inflammatory response but also in the degradation of the bone. Therefore,
      a lack of production of TNFalpha by the cells of the immune system in contact
      with a candidate material for implant design is an indication of the acceptance
      of the biomaterial, and predicts the inflammatory response responsible for
      implant intolerance. There is no standard laboratory test to evaluate an
      individual response of a patient to a possible implant, although the use of
      peripheral blood mononuclear cells (PBMCs) has been suggested. Here, we evaluated
      the biocompatibility and cytotoxicity of films made of polyhydroxybutyrate (PHB)
      reinforced with different concentrations of cellulose nanowhiskers (CNWs) using
      PBMCs from healthy donors. Cells from healthy donors were cultured in the
      presence of films of the biomaterial during 24 h and 7 d and the cell viability
      and proinflammatory cytokines TNFalpha and IL6 production were measured. We
      confirmed that PHB, CNWs and the reinforced blends (PHB/CNWs) are safe and lack
      cytotoxicity in human cells, which make them good candidates for implant
      materials.

PMID- 29376502
TI  - Prediction and early detection of delirium in the intensive care unit by using
      heart rate variability and machine learning.
AB  - OBJECTIVE: Delirium is an important syndrome found in patients in the intensive
      care unit (ICU), however, it is usually under-recognized during treatment. This
      study was performed to investigate whether delirious patients can be successfully
      distinguished from non-delirious patients by using heart rate variability (HRV)
      and machine learning. APPROACH: Electrocardiography data of 140 patients was
      acquired during daily ICU care, and HRV data were analyzed. Delirium, including
      its type, severity, and etiologies, was evaluated daily by trained psychiatrists.
      HRV data and various machine learning algorithms including linear support vector
      machine (SVM), SVM with radial basis function (RBF) kernels, linear extreme
      learning machine (ELM), ELM with RBF kernels, linear discriminant analysis, and
      quadratic discriminant analysis were utilized to distinguish delirium patients
      from non-delirium patients. MAIN RESULTS: HRV data of 4797 ECGs were included,
      and 39 patients had delirium at least once during their ICU stay. The maximum
      classification accuracy was acquired using SVM with RBF kernels. Our prediction
      method based on HRV with machine learning was comparable to previous delirium
      prediction models using massive amounts of clinical information. SIGNIFICANCE:
      Our results show that autonomic alterations could be a significant feature of
      patients with delirium in the ICU, suggesting the potential for the automatic
      prediction and early detection of delirium based on HRV with machine learning.

PMID- 29376503
TI  - On the correct use of stepped-sine excitations for the measurement of time
      varying bioimpedance.
AB  - Many electrochemical/bioelectrochemical systems are intrinsically nonstationary
      and are affected by time-dependent phenomena. The requirement of stationarity in
      the classical version of impedance spectroscopy appears to be in conflict with
      the essential properties of the object, therefore a post-experimental
      mathematical/analytical procedure is necessary for the reconstruction of the
      'true' impedance spectra. In this communication, a method for the correction of
      the impedance data is discussed.

PMID- 29376504
TI  - Diagnostic reference levels for common computed tomography (CT) examinations:
      results from the first Nigerian nationwide dose survey.
AB  - PURPOSE: To explore doses from common adult computed tomography (CT) examinations
      and propose national diagnostic reference levels (nDRLs) for Nigeria. MATERIALS
      AND METHODS: This retrospective study was approved by the Nnamdi Azikiwe
      University and University Teaching Hospital Institutional Review Boards (IRB:
      NAUTH/CS/66/Vol8/84) and involved dose surveys of adult CT examinations across
      the six geographical regions of Nigeria and Abuja from January 2016 to August
      2017. Dose data of adult head, chest and abdomen/pelvis CT examinations were
      extracted from patient folders. The median, 75th and 25th percentile CT dose
      index volume (CTDIvol) and dose-length-product (DLP) were computed for each of
      these procedures. Effective doses (E) for these examinations were estimated using
      the k conversion factor as described in the ICRP publication 103 (EDLP = k *
      DLP). RESULTS: The proposed 75th percentile CTDIvol for head, chest, and
      abdomen/pelvis are 61 mGy, 17 mGy, and 20 mGy, respectively. The corresponding
      DLPs are 1310 mGy.cm, 735 mGy.cm, and 1486 mGy.cm respectively. The effective
      doses were 2.75 mSv (head), 10.29 mSv (chest), and 22.29 mSv (abdomen/pelvis).
      CONCLUSION: Findings demonstrate wide dose variations within and across centres
      in Nigeria. The results also show CTDIvol comparable to international standards,
      but considerably higher DLP and effective doses.

PMID- 29376505
TI  - Ascent of atomic force microscopy as a nanoanalytical tool for exosomes and other
      extracellular vesicles.
AB  - Over the last 30 years, atomic force microscopy (AFM) has made several
      significant contributions to the field of biology and medicine. In this review,
      we draw our attention to the recent applications and promise of AFM as a high
      resolution imaging and force sensing technology for probing subcellular vesicles:
      exosomes and other extracellular vesicles. Exosomes are naturally occurring
      nanoparticles found in several body fluids such as blood, saliva, cerebrospinal
      fluid, amniotic fluid and urine. Exosomes mediate cell-cell communication,
      transport proteins and genetic content between distant cells, and are now known
      to play important roles in progression of diseases such as cancers,
      neurodegenerative disorders and infectious diseases. Because exosomes are smaller
      than 100 nm (about 30-120 nm), the structural and molecular characterization of
      these vesicles at the individual level has been challenging. AFM has revealed a
      new degree of complexity in these nanosized vesicles and generated growing
      interest as a nanoscale tool for characterizing the abundance, morphology,
      biomechanics, and biomolecular make-up of exosomes. With the recent interest in
      exosomes for diagnostic and therapeutic applications, AFM-based characterization
      promises to contribute towards improved understanding of these particles at the
      single vesicle and sub-vesicular levels. When coupled with complementary methods
      like optical super resolution STED and Raman, AFM could further unlock the
      potential of exosomes as disease biomarkers and as therapeutic agents.

PMID- 29376506
TI  - Bulla formation at the tuberculin skin test site in a patient with bullous
      pemphigoid: Koebnerization or severe delayed-type hypersensitivity?

PMID- 29376507
TI  - Oral ulcers in heart transplant patient.

PMID- 29376508
TI  - A subungual angiokeratoma with characteristic clinical and dermoscopic features.

PMID- 29376509
TI  - Total serum immunoglobulin E level and specific allergens in adults with skin
      diseases.
AB  - Background: Immunoglobulin E (IgE) plays an important role in allergic diseases.
      Although several studies have shown the association of serum total IgE and
      allergen-specific IgE levels with allergic dermatological diseases such as atopic
      dermatitis, there are few studies addressing this association for skin diseases
      in general. Aims: We sought to evaluate IgE levels in skin diseases and
      investigate the differences based on the disease type and clinical factors such
      as gender and age. Methods: Data from 2836 patients who visited the dermatologic
      clinic of the Konkuk University Hospital, Seoul, Republic of Korea for 4 years
      were reviewed to document IgE levels and clinical information. IgE levels were
      collated with the type of skin disease, gender, and age. Results: Patients with
      atopic dermatitis had a much higher total IgE level and were more susceptible to
      allergens as compared to other disease groups. Patients in other disease groups
      showed no significant differences in IgE levels. Men showed higher total IgE
      levels but the gender differences decreased with increasing age. Limitations: The
      data were collected from patients at a referral centre and thus may not represent
      the general population of dermatologic patients. There was a lack of information
      regarding factors that could potentially influence IgE levels such as smoking
      history and disease severity. Conclusions: The results suggest that there are
      physiological or environmental differences in IgE-mediated immune responses
      between males and females. Also, except for atopic dermatitis, there were no
      clinical differences in the IgE levels among various skin diseases.

PMID- 29376510
TI  - A solitary fibrofolliculoma occurring in an unusual location.

PMID- 29376511
TI  - Scholarships and travel grants for residents and young dermatologists from India.

PMID- 29376512
TI  - Cutaneous angiosarcoma in a patient with systemic sclerosis: First case from
      India.

PMID- 29376513
TI  - Evaluating the impact of an injury prevention measure regarding different
      sociodemographic factors.
AB  - BACKGROUND: Road traffic collisions (RTC) remain a major problem especially among
      young road users. Injury prevention measures and licensing systems have
      increasingly been developed to counteract some of the negative effects of RTCs in
      youth. The Prevent Alcohol and Risk Related Trauma in Youth (P.A.R.T.Y.) program
      is an injury prevention program that promotes prevention through reality
      education. In this study, the impact of the program on different sociodemographic
      subgroups of school students was analyzed. The aim was to find out which
      subgroups were influenced the most and how improvements to the program can be
      made. METHODS: Evaluation was performed in a pre-post-intervention setting by
      means of a standardized questionnaire. The questionnaire contained three
      different sections with a total of 22 questions to identify students' responses
      regarding risk-behavior and risk-assessment. Evaluation was done at two different
      points on the same day (pre-and post-intervention). Data were analyzed with a
      focus on gender, age, residential area and level of education. Cronbach's alpha
      was used to check all questions for reliability. Data were analyzed using the t
      test and the Wilcoxon signed-rank test with significance defined as p less than
      0.05. RESULTS: The study sample contains 193 students (range 14-17 years of age,
      44% male). Female students show better results regarding risk-behavior and risk
      awareness. The same applies to students of a higher educational level. And
      students >= 16 years showed significantly better results in all three sections
      compared to younger students. CONCLUSIONS: Morbidity and mortality due to RTCs is
      a major problem in the group of young road users. Especially male road users
      between 14 and 17 years of age with a low educational level are at high risk to
      sustain road traffic injuries. Our results show that the P.A.R.T.Y. program has a
      stronger effect on young female students. Additionally, a significant effect was
      measured on students >= 16 years of age and on students with a higher educational
      level. Prevention measures need to be evaluated and further improved particularly
      in order to address the high-risk group of young, male road users with a lower
      educational status.

PMID- 29376515
TI  - Experiences of Social Support Among Chinese Women with Breast Cancer: A
      Qualitative Analysis Using a Framework Approach.
AB  - BACKGROUND Breast cancer and its treatment provoke a series of emotional changes
      in patients during their breast cancer journeys. Social support is critical in
      helping women cope with their negative emotional responses. However, few studies
      have described the experiences of women with breast cancer within the Chinese
      context. This qualitative study explored the experiences of Chinese women with
      breast cancer regarding social support. MATERIAL AND METHODS This qualitative
      study was based on constructivism epistemology. Chinese women with breast cancer
      were invited to interview between June and August 2016. Purposive sampling was
      used, and the women were recruited until data saturation was reached (n=25).
      RESULTS We found that all participants expressed the importance of social support
      during their breast cancer journeys. The thematic framework of social support was
      identified, which included the following 4 interrelated themes: providers, types
      of support, outcomes of support, and challenges for care. CONCLUSIONS Social
      support is important in the health care of women living with breast cancer.
      Healthcare professionals should provide more individualized support and care to
      women during this vulnerable period.

PMID- 29376514
TI  - The comparison of socioeconomic status, perceived social support and mental
      status in women of reproductive age experiencing and not experiencing domestic
      violence in Iran.
AB  - BACKGROUND: Given the significant health effects of domestic violence against
      women, the present study was conducted in 2016, in Tehran, Iran in order to
      compare the socioeconomic status, perceived social support and mental status in
      women of reproductive age experiencing and not experiencing domestic violence.
      METHODS: This descriptive-analytical cross-sectional study was conducted on 500
      women. The data collection tools used included questionnaires: demographic
      information, Socioeconomic, Beck's Depression, Spielberger's Anxiety, Cohen's
      Perceived Stress, Sarason's Perceived Social Support and WHO's Domestic Violence
      Inventory. RESULTS: The results showed that 43.2% of women said they had
      experienced at least one case of domestic violence, among which 16.4%, 15% and
      36.6% of women had experienced physical, sexual and emotional-verbal types of
      violence, respectively. The mean age (p less than 0.001) and educational level
      (p=0/018) of violated women and their spouses (p less than 0.001) were lower than
      those of non-violated women. Furthermore, violated women experienced lower
      socioeconomic status (p less than 0.05), higher perceived stress (p less than
      0.008), higher depression (p less than 0.001), and higher overt anxiety (0.002.
      They also perceived lower levels of social support (p less than 0.001).
      CONCLUSIONS: The issue of domestic violence was rather prevalent in the
      participants of the present study, particularly the younger, less educated and
      more socioeconomically deprived communities and families.

PMID- 29376516
TI  - Corrigendum: Dislocation Strengthening without Ductility Trade-off in Metastable
      Austenitic Steels.
AB  - This corrects the article DOI: 10.1038/srep35345.

PMID- 29376517
TI  - Corrigendum: Application of a novel phosphinothricin N-acetyltransferase (RePAT)
      gene in developing glufosinate-resistant rice.
AB  - This corrects the article DOI: 10.1038/srep21259.

PMID- 29376518
TI  - Corrigendum: Application of Machine-Learning Models to Predict Tacrolimus Stable
      Dose in Renal Transplant Recipients.
AB  - This corrects the article DOI: 10.1038/srep42192.

PMID- 29376522
TI  - Adipose tissue: New tissue processing technique for adipose tissues.

PMID- 29376521
TI  - Tumour budding in colorectal cancer: molecular rationale for clinical
      translation.

PMID- 29376520
TI  - Targeting minimal residual disease: a path to cure?
AB  - Therapeutics that block kinases, transcriptional modifiers, immune checkpoints
      and other biological vulnerabilities are transforming cancer treatment. As a
      result, many patients achieve dramatic responses, including complete
      radiographical or pathological remission, yet retain minimal residual disease
      (MRD), which results in relapse. New functional approaches can characterize
      clonal heterogeneity and predict therapeutic sensitivity of MRD at a single-cell
      level. Preliminary evidence suggests that iterative detection, profiling and
      targeting of MRD would meaningfully improve outcomes and may even lead to cure.

PMID- 29376524
TI  - Risk factors: Breastfeeding reduces risk of type 2 diabetes mellitus.

PMID- 29376519
TI  - Fanconi anaemia and cancer: an intricate relationship.
AB  - Fanconi anaemia (FA) is a genetic disorder that is characterized by bone marrow
      failure (BMF), developmental abnormalities and predisposition to cancer. Together
      with other proteins involved in DNA repair processes and cell division, the FA
      proteins maintain genome homeostasis, and germline mutation of any one of the
      genes that encode FA proteins causes FA. Monoallelic inactivation of some FA
      genes, such as FA complementation group D1 (FANCD1; also known as the breast and
      ovarian cancer susceptibility gene BRCA2), leads to adult-onset cancer
      predisposition but does not cause FA, and somatic mutations in FA genes occur in
      cancers in the general population. Carcinogenesis resulting from a dysregulated
      FA pathway is multifaceted, as FA proteins monitor multiple complementary genome
      surveillance checkpoints throughout interphase, where monoubiquitylation of the
      FANCD2-FANCI heterodimer by the FA core complex promotes recruitment of DNA
      repair effectors to chromatin lesions to resolve DNA damage and mitosis. In this
      Review, we discuss how the FA pathway safeguards genome integrity throughout the
      cell cycle and show how studies of FA have revealed opportunities to develop
      rational therapeutics for this genetic disease and for malignancies that acquire
      somatic mutations within the FA pathway.

PMID- 29376525
TI  - Ligand mediated evolution of size dependent magnetism in cobalt nanoclusters.
AB  - We use density functional theory to model the impact of a ligand shell on the
      magnetic properties of CoN (15 <= N <= 55) nanoclusters. We study three different
      ligand shells on each nanocluster core size, each known to have different
      electronic interactions with the surface: pure Cl ligand shells (X-type), pure
      PH3 ligand shells (L-type), and two component ligand shells with mixtures of Cl
      and PH3 ligands. The simulations show that the identity, arrangement, and total
      coverage of the ligand shell controls the distribution of local magnetic moments
      across the CoN core. On the surface of an unpassivated CoN nanocluster, the Co-Co
      coordination number (CN) is known to determine the local magnetic moments. Upon
      the introduction of a ligand, the Co-Co CN remains important, however the nature
      of the metal-ligand bond changes the extent to which increasing Co-Co CN quenches
      magnetism. Further, we identify an additional and significant long-range impact
      on local magnetic moments (LMM) from the PH3 ligand shells. Thus, we establish
      important design principles of magnetic nanoclusters, where ligand shell
      chemistry mediates the distribution of LMMs across a CoNLM nanocluster, allowing
      a route to rational design of specific magnetic properties.

PMID- 29376526
TI  - High CO2 absorption by diamino protic ionic liquids using azolide anions.
AB  - For the first time, several low-viscosity diamino protic ionic liquids (DPILs),
      based on azolides as anions (pyrazolide, imidazolide and triazolide) have been
      synthesised, characterised and evaluated for CO2 capture. The results reveal that
      these ionic liquids rapidly absorb CO2 to more than 20% w/w pointing towards
      equimolar absorption.

PMID- 29376523
TI  - Osteocalcin in the brain: from embryonic development to age-related decline in
      cognition.
AB  - A remarkable, unexpected aspect of the bone-derived hormone osteocalcin is that
      it is necessary for both brain development and brain function in the mouse, as
      its absence results in a profound deficit in spatial learning and memory and an
      exacerbation of anxiety-like behaviour. The regulation of cognitive function by
      osteocalcin, together with the fact that its circulating levels decrease in
      midlife compared with adolescence in all species tested, raised the prospect that
      osteocalcin might be an anti-geronic hormone that could prevent age-related
      cognitive decline. As presented in this Review, recent data indicate that this is
      indeed the case and that osteocalcin is necessary for the anti-geronic activity
      recently ascribed to the plasma of young wild-type mice. The diversity and
      amplitude of the functions of osteocalcin in the brain, during development and
      postnatally, had long called for the identification of its receptor in the brain,
      which was also recently achieved. This Review presents our current understanding
      of the biology of osteocalcin in the brain, highlighting the bony vertebrate
      specificity of the regulation of cognitive function and pointing toward where
      therapeutic opportunities might exist.

PMID- 29376527
TI  - Selective sensing of 2,4,6-trinitrophenol (TNP) in aqueous media with
      "aggregation-induced emission enhancement" (AIEE)-active iridium(iii) complexes.
AB  - A series of new phosphorescent cyclometalated iridium(iii) complexes which
      possess aggregation-induced emission enhancement (AIEE) detect 2,4,6
      trinitrophenol (TNP) selectively with high quenching constants in aqueous media.
      The sensing mechanism was systematically investigated by mass spectrometry, 1H
      and 19F NMR spectroscopy. X-ray crystal structure analysis reveals an O-HO
      interaction between TNP and the ancillary ligand which explains the high
      selectivity for TNP compared to other nitro-aromatics.

PMID- 29376528
TI  - Supramolecular assemblies through host-guest complexation between cucurbiturils
      and an amphiphilic guest molecule.
AB  - We report the formation of supramolecular complexation between cucurbit[n]urils
      (CBn) and an amphiphilic pyridinium-functionalized anthracene (AnPy) in aqueous
      solution. The CB7 cavity is capable of accommodating the pyridinium moiety, while
      CB8 can encapsulate the pyridinium and anthracene moieties at once. The
      encapsulation of AnPy by CB7 leads to the formation of nanoparticles, while the
      complexation of AnPy with CB8 leads to the formation of nanorods.

PMID- 29376529
TI  - Gateway state-mediated, long-range tunnelling in molecular wires.
AB  - If the factors controlling the decay in single-molecule electrical conductance G
      with molecular length L could be understood and controlled, then this would be a
      significant step forward in the design of high-conductance molecular wires. For a
      wide variety of molecules conducting by phase coherent tunnelling, conductance G
      decays with length following the relationship G = Ae-betaL. It is widely accepted
      that the attenuation coefficient beta is determined by the position of the Fermi
      energy of the electrodes relative to the energy of frontier orbitals of the
      molecular bridge, whereas the terminal anchor groups which bind to the molecule
      to the electrodes contribute to the pre-exponential factor A. We examine this
      premise for several series of molecules which contain a central conjugated moiety
      (phenyl, viologen or alpha-terthiophene) connected on either side to alkane
      chains of varying length, with each end terminated by thiol or thiomethyl anchor
      groups. In contrast with this expectation, we demonstrate both experimentally and
      theoretically that additional electronic states located on thiol anchor groups
      can significantly decrease the value of beta, by giving rise to resonances close
      to EF through coupling to the bridge moiety. This interplay between the gateway
      states and their coupling to a central conjugated moiety in the molecular bridges
      creates a new design strategy for realising higher-transmission molecular wires
      by taking advantage of the electrode-molecule interface properties.

PMID- 29376530
TI  - Synthesis and properties of MoCl4 complexes with thio- and seleno-ethers and
      their use for chemical vapour deposition of MoSe2 and MoS2 films.
AB  - Treatment of trans-[MoCl4(MeCN)2] with L (L = Me2S, Me2Se, THT, 1/2MeSCH2CH2SMe)
      in CH2Cl2 solution, or reaction of MoCl5 with excess L' (L' = nBu2S, nBu2Se,
      1/2MeSCH2CH2SMe, 1/2iPrSCH2CH2SiPr, 1/2MeSCH2CH2CH2SMe, 1/2MeSeCH2CH2CH2SeMe) in
      MeCN, produces the Mo(iv) complexes, [MoCl4(L)2] and [MoCl4(L')2], respectively,
      in good yield. The new complexes have been characterised by IR and UV-vis
      spectroscopy, elemental analysis and magnetic measurements, whilst crystal
      structure analyses of trans-[MoCl4(Me2S)2], cis-[MoCl4{RS(CH2)2SR}] (R = Me, iPr)
      and cis-[MoCl4{MeS(CH2)3SMe}] confirmed their identities and distorted octahedral
      geometries. The potential of [MoCl4(nBu2E)2] (E = S, Se) as the first examples of
      molybdenum halide derived single source CVD precursors for the growth of MoE2
      thin films was first probed by TGA, which showed multi-step decomposition
      processes, with the masses of the final residues consistent with MoSe2 (E = Se)
      and MoCl4 (E = S), respectively. Low pressure CVD experiments conducted at 750 
      degrees C (E = S) and 525  degrees C (E = Se) gave silvery and golden yellow
      films, respectively. Grazing incidence and in plane XRD data confirmed these to
      be 2H-MoE2, whilst the texture of the MoSe2 was investigated using pole figure
      measurements. SEM and EDX data, optical and Raman data on the films are also
      reported.

PMID- 29376531
TI  - Structure and rheology of polyelectrolyte complex coacervates.
AB  - Scattering investigations of the structure and chain conformations, and the
      rheological properties of polyelectrolyte complexes (PECs) comprising model
      polyelectrolytes are presented. The use of charged polypeptides - (poly)-lysine
      and (poly)-glutamic acid with identical backbones allowed for facile tuning of
      the system parameters, including chain length, side-chain functionality, and
      chirality. Systematic studies using small-angle X-ray scattering (SAXS) of liquid
      PEC coacervates revealed a physical description of these materials as strongly
      screened semidilute polyelectrolyte solutions comprising oppositely charged
      chains. At the same time, solid PECs were found to be composed of hydrogen
      bonding driven stiff ladder-like structures. While the coacervates behaved akin
      to semidilute polyelectrolyte solutions upon addition of salt, the solids were
      largely unaffected by it. Rheology measurements of PEC coacervates revealed a
      terminal relaxation regime, with an unusual plateauing of the storage modulus at
      low oscillation frequencies. The plateau may be ascribed to a combination of
      instrumental limitations and the long-range electrostatic interactions
      contributing to weak energy storage modes. Excellent superposition of the dynamic
      moduli was achieved by a time-salt superposition. The shift factors, however,
      varied more strongly than previously reported with added salt concentration.

PMID- 29376532
TI  - Anion transport by ortho-phenylene bis-ureas across cell and vesicle membranes.
AB  - Ortho-Phenylene bis-ureas serve as anionophores in cells expressing halide
      sensitive yellow fluorescent protein, as well as in synthetic vesicles.
      Activities can reach high levels, and are strongly dependent on the
      deliverability of the transporters.

PMID- 29376533
TI  - Purely-elastic flow instabilities and elastic turbulence in microfluidic cross
      slot devices.
AB  - We experimentally investigate the dynamics of viscoelastic fluid flows in cross
      slot microgeometries under creeping flow conditions. We focus on the unsteady
      flow regime observed at high Weissenberg numbers (Wi) with the purpose of
      understanding the underlying flow signature of elastic turbulence. The effects of
      the device aspect ratio and fluid rheology on the unsteady flow state are
      investigated. Visualization of the flow patterns and time-resolved micro-particle
      image velocimetry were carried out to study the fluid flow behavior for a wide
      range of Weissenberg numbers. A periodic flow behavior is observed at low
      Weissenberg numbers followed by a more complex dynamics as Wi increases,
      eventually leading to the onset of elastic turbulence for very high Weissenberg
      numbers.

PMID- 29376534
TI  - Water ring-bouncing on repellent singularities.
AB  - Texturing a flat superhydrophobic substrate with point-like superhydrophobic
      macrotextures of the same repellency makes impacting water droplets take off as
      rings, which leads to shorter bouncing times than on a flat substrate. We
      investigate the contact time reduction on such elementary macrotextures through
      experiment and simulations. We understand the observations by decomposing the
      impacting drop reshaped by the defect into sub-units (or blobs) whose size is
      fixed by the liquid ring width. We test the blob picture by looking at the
      reduction of contact time for off-centered impacts and for impacts in grooves
      that produce liquid ribbons where the blob size is fixed by the width of the
      channel.

PMID- 29376535
TI  - Correction: Adaptable piezoelectric hemispherical composite strips using a
      scalable groove technique for a self-powered muscle monitoring system.
AB  - Correction for 'Adaptable piezoelectric hemispherical composite strips using a
      scalable groove technique for a self-powered muscle monitoring system' by
      Nagamalleswara Rao Alluri et al., Nanoscale, 2018, 10, 907-913.

PMID- 29376536
TI  - A stable thiolato-CuI-thiolato triple linkage that bridges two cobalt(iii)
      centres.
AB  - Treatment of Lambda-fac-[Co(d-pen-N,S)3]3- (d-H2pen = d-penicillamine) with Cu+
      in water gave a stable CoCu complex, LambdaLambda-[Co2Cu3(d-pen)6]3- ([1]3-),
      having three thiolato-copper(i)-thiolato moieties that bridge two cobalt(iii)
      centres. Complex [1]3- was isolated as a coordination polymer of Na3[1], which
      was converted to a complex salt of [Cr(H2O)6][1] by treatment with Cr(NO3)3.

PMID- 29376537
TI  - The influence of anion chemistry on the ionic conductivity and molecular dynamics
      in protic organic ionic plastic crystals.
AB  - Proton conductors are widely used in different electrochemical devices including
      fuel cells and redox flow batteries. Compared to conventional proton conducting
      polymer membranes, protic organic ionic plastic crystal (POIPC) is a novel solid
      state proton conductor with high proton conductivity even under anhydrous
      conditions. In this work, different organic protic salts based on the same parent
      di-functional cation with different anions were synthesized and characterized. It
      is found that the di-protonated cation plays an important role in defining the
      thermal properties, leading to stronger plastic crystal behavior and a higher
      melting point. Static solid-state NMR and the synchrotron XRD results show that
      the di-protonated cation allows greater dynamics in the crystal in contrast to
      the mono-protonated counterparts. The 1-(N,N-dimethylammonium)-2-(ammonium)ethane
      triflate ([DMEDAH2][Tf]2) has the highest ionic conductivity of 1.1 * 10-4 S cm-1
      at 50  degrees C, whereas the bis(trifluoromethanesulfonyl)amide counterpart
      [DMEDAH2][TFSA]2 has the lowest ionic conductivity (2.8 * 10-7 S cm-1 at 50 
      degrees C) with no measureable mobile ion component at this temperature. The
      fraction of mobile species is significantly suppressed in the TFSA containing
      salts as against the Tf systems.

PMID- 29376538
TI  - The negative Poisson's ratio in graphene-based carbon foams.
AB  - Using molecular dynamics simulations, we find an in-plane negative Poisson's
      ratio intrinsically existing in the graphene-based three-dimensional (3D) carbon
      foams (CFs) when they are compressed uniaxially. Our study shows that the
      negative Poisson's ratio in the present CFs is attributed to their unique
      molecular structures and triggered by the buckling of the CF structures. This
      mechanism makes the negative Poisson's ratio of CFs strongly depend on their cell
      length, which offers us an efficient means to tune the negative Poisson's ratio
      in nanomaterials. Moreover, as the buckling modes of CFs are topographically
      different when they are compressed in different directions, their negative
      Poisson's ratio is found to be strongly anisotropic, which is in contrast to the
      isotropic positive Poisson's ratio observed in CFs prior to buckling. The
      discovery of the intrinsic negative Poisson's ratio in 3D CFs will significantly
      expand the family of auxetic nanomaterials. Meanwhile, the mechanism of nano
      auxetics proposed here may open up a door to manufacture new auxetic materials on
      the nanoscale.

PMID- 29376539
TI  - Synthesis of oligosaccharides related to galactomannans from Aspergillus
      fumigatus and their NMR spectral data.
AB  - The synthesis of model oligosaccharides related to antigenic galactomannans of
      the dangerous fungal pathogen Aspergillus fumigatus has been performed employing
      pyranoside-into-furanoside (PIF) rearrangement and controlled O(5) -> O(6)
      benzoyl migration as key synthetic methods. The prepared compounds along with
      some previously synthesized oligosaccharides were studied by NMR spectroscopy
      with the full assignment of 1H and 13C signals and the determination of 13C NMR
      glycosylation effects. The obtained NMR database on 13C NMR chemical shifts for
      oligosaccharides representing galactomannan fragments forms the basis for further
      structural analysis of galactomannan related polysaccharides by a non-destructive
      approach based on the calculation of the 13C NMR spectra of polysaccharides by
      additive schemes.

PMID- 29376540
TI  - Selective protein unfolding: a universal mechanism of action for the development
      of irreversible inhibitors.
AB  - High-throughput differential scanning fluorimetry of GFP-tagged proteins (HT-DSF
      GTP) was applied for the identification of novel enzyme inhibitors acting by a
      mechanism termed: selective protein unfolding (SPU). Four different protein
      targets were interrogated with the same library to identify target-selective
      hits. Several hits selectively destabilized bacterial biotin protein ligase.
      Structure-activity relationship data confirmed a structure-dependent mechanism of
      protein unfolding. Simvastatin and altenusin were confirmed to irreversibly
      inactivate biotin protein ligase. The principle of SPU combined with HT-DSF-GTP
      affords an invaluable and innovative workflow for the identification of new
      inhibitors with potential applications as antimicrobials and other biocides.

PMID- 29376541
TI  - Application of a coupled smoothed particle hydrodynamics (SPH) and coarse-grained
      (CG) numerical modelling approach to study three-dimensional (3-D) deformations
      of single cells of different food-plant materials during drying.
AB  - Numerical modelling has gained popularity in many science and engineering streams
      due to the economic feasibility and advanced analytical features compared to
      conventional experimental and theoretical models. Food drying is one of the areas
      where numerical modelling is increasingly applied to improve drying process
      performance and product quality. This investigation applies a three dimensional
      (3-D) Smoothed Particle Hydrodynamics (SPH) and Coarse-Grained (CG) numerical
      approach to predict the morphological changes of different categories of food
      plant cells such as apple, grape, potato and carrot during drying. To validate
      the model predictions, experimental findings from in-house experimental
      procedures (for apple) and sources of literature (for grape, potato and carrot)
      have been utilised. The subsequent comaprison indicate that the model predictions
      demonstrate a reasonable agreement with the experimental findings, both
      qualitatively and quantitatively. In this numerical model, a higher computational
      accuracy has been maintained by limiting the consistency error below 1% for all
      four cell types. The proposed meshfree-based approach is well-equipped to predict
      the morphological changes of plant cellular structure over a wide range of
      moisture contents (10% to 100% dry basis). Compared to the previous 2-D meshfree
      based models developed for plant cell drying, the proposed model can draw more
      useful insights on the morphological behaviour due to the 3-D nature of the
      model. In addition, the proposed computational modelling approach has a high
      potential to be used as a comprehensive tool in many other tissue morphology
      related investigations.

PMID- 29376542
TI  - Construction of iron oxide nanoparticle-based hybrid platforms for tumor imaging
      and therapy.
AB  - The aim of this original review is to highlight and analyze the most recent
      progress and challenges in the synthesis and surface modifications of
      superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) for multimodal imaging
      and therapy applications, which represent important fields in medicine in general
      and cancer in particular. Thus, the oncology domain is rapidly moving to a more
      personalized medicine including precision imaging and theranostic approaches.
      Novel biocompatible Fe3O4 nanoparticulate systems have been designed for enhanced
      and targeted cellular uptake by surface layer coating modifications, to have
      improved r2 relaxivity for sensitive magnetic resonance (MR) imaging
      applications, to have the ability to be used for dual mode imaging, and to be
      used for imaging-guided cancer therapy. In this review, we analyzed in depth the
      new strategies for generating biocompatible multifunctional Fe3O4 nanoplatforms
      for both the diagnosis and therapy of cancer.

PMID- 29376543
TI  - Solvation effects on the vibrational modes in hydrated bicarbonate clusters.
AB  - HCO3-(H2O)n clusters provide a model system to understand the solvation
      interaction between the bicarbonate ion and water. Based on harmonic analysis, ab
      initio molecular dynamics simulations, and comparison with infrared multiple
      photon dissociation spectra and with previous results on H2PO4-(H2O)n, the
      solvation effects on the vibrational modes of HCO3-(H2O)n are analyzed. Hydrogen
      bond interactions have a significant impact on the vibration, especially when a
      hydrogen atom is directly involved in a particular mode. The COH bending mode is
      flattened, when the COH group is solvated by water molecules. The emergence of
      broad water libration modes indicates the aggregation of water molecules and the
      formation of a surface structure with bicarbonate on the surface.

PMID- 29376544
TI  - Microkinetic model for reaction and diffusion of titanium interstitial atoms near
      a TiO2(110) surface.
AB  - Semiconductor surfaces provide efficient pathways for injecting native point
      defects into the underlying bulk. In the case of interstitial atoms in rutile,
      the TiO2(110) surface exemplifies this behavior, although extended defects in the
      bulk such as platelets and crystallographic shear planes act as net sources or
      sinks depending upon specific conditions. The present work constructs a
      quantitative microkinetic model to describe diffusion and based upon isotopic gas
      solid exchange experiments. Key activation barriers for are 0.55 eV for surface
      injection, 0.50 eV for site-to-site hopping diffusion, and 3.3 eV for
      dissociation of titanium interstitials from extended defects.

PMID- 29376545
TI  - Idiopathic pulmonary fibrosis in a Swiss interstitial lung disease reference
      centre.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) differs substantially from other
      idiopathic interstitial pneumonias regarding disease trajectory and the
      appropriate management strategies, making meticulous diagnosis essential.
      However, patient characteristics and clinical practice vary between clinical
      trials, and real life and registries provide the opportunity to critically
      analyse current clinical practices in order to ultimately improve patient care.
      METHODS: We aimed to identify characteristics of our baseline IPF cohort at
      initiation of a web-based registry for patients with idiopathic interstitial
      pneumonia. Baseline and 6-month follow-up data from all consecutive IPF patients
      consulting at our centre over 2 years were analysed. RESULTS: Forty IPF patients
      were included for baseline and 23 for longitudinal analysis. Besides many
      similarities to other IPF populations, our cohort included considerably fewer
      women. Forced vital capacity impairment in our cohort was more severe and
      mortality prediction poorer than in clinical trials, which emphasises the
      importance to confirm the applicability of clinical trial results with data from
      real life settings. CONCLUSION: Registries for rare diseases such as IPF are a
      valuable resource for studying the course of the disease under current compliance
      with diagnostic and treatment guidelines and to appreciate local epidemiological
      particularities.

PMID- 29376546
TI  - Hospital discharge of patients with ongoing care needs: a cross-sectional study
      using data from a city hospital under SwissDRG.
AB  - AIM OF THE STUDY: Switzerland introduced the SwissDRG in 2012. The goal of this
      reimbursement system was to promote cost containment and efficiency in hospital
      care. To ensure that patients with care needs are not released prematurely
      because of constraints under the new hospital financing system, the Swiss law on
      Acute and Transitional Care (ATC) was introduced one year earlier. The objective
      of the present study was to investigate the impact of ATC and its effects on
      discharge of patients with persisting care needs after hospitalisation. METHODS:
      Social service workers, nurses and palliative care team members at a Swiss
      municipal hospital were asked to complete a four-page closed-ended questionnaire
      about patients who require care after their hospital discharge. This included
      questions on discharge management, their perceptions of the appropriateness of
      discharge timing and details about conflicts regarding discharge. Information on
      length of stay, discharge location, age and sex was extracted from hospital
      records and matched to the information from the questionnaires. Demographic data
      are presented descriptively, differences between patients released to ATC and
      patients released elsewhere (home, nursing home, rehabilitation, etc.) were
      evaluated with chi-square tests. Logistic regression analyses were performed to
      evaluate differences between those sent to ATC and rehabilitation with age,
      length of stay and sex as predictors. RESULTS: A total 1410 of valid
      questionnaires were collected, comprised of 746 female patients (52.9%) and 664
      male patients (47.1%). The mean age of our patient cohort was 73.2 years (SD
      15.1), and the mean hospital stay was 12.8 days (SD 9.1). After their hospital
      stay, 553 patients (39.2%) returned home either alone, or with the help of family
      members or Spitex. More than a quarter of the sample, 387 (27.4%) patients, was
      sent to rehabilitation. Less than a fifth, 199 (14.1%) patients, received ATC in
      an inpatient institution (e.g., nursing home). Compared with patients released
      elsewhere, significantly more problems/conflicts with regard to hospital
      discharge were reported for ATC patients (28.6 vs 20.6%, p = 0.01) and their
      relatives (12.6 vs 7.2%, p = 0.01). Women had a higher probability of being
      discharged to ATC (OR 1.522, p = 0.014) and a lower chance of receiving
      rehabilitation upon discharge (OR 0.733, p = 0.014). CONCLUSION: The study
      identified important concerns related to receiving ATC after a hospital stay,
      that is, more problems/conflicts occur with patients discharged to ATC and that
      the introduction of ATC might particularly disadvantage female patients, who are
      less likely to receive rehabilitation care.

PMID- 29376547
TI  - Digital health: meeting the ethical and policy challenges.
AB  - Digital health encompasses a wide range of novel digital technologies related to
      health and medicine. Such technologies rely on recent advances in the collection
      and analysis of ever increasing amounts of data from both patients and healthy
      citizens. Along with new opportunities, however, come new ethical and policy
      challenges. These range from the need to adapt current evidence-based standards,
      to issues of privacy, oversight, accountability and public trust as well as
      national and international data governance and management. This review
      illustrates key issues and challenges facing the rapidly unfolding digital health
      paradigm and reflects on the impact of big data in medical research and clinical
      practice both internationally and in Switzerland. It concludes by emphasising
      five conditions that will be crucial to fulfil in order to foster innovation and
      fair benefit sharing in digital health.

PMID- 29376548
TI  - Vitamin D levels in Swiss breast cancer survivors.
AB  - BACKGROUND: Cholecalciferol (vitamin D3) is widely supplemented in breast cancer
      survivors because of the role of vitamin D in multiple health outcomes. METHODS:
      We conducted an observational study in 332 women in Eastern Switzerland with
      early, i.e., nonmetastatic breast cancer. Tumour-, patient-related and
      sociodemographic variables were recorded. Cholecalciferol intake and serum 25
      hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were
      measured at the first visit (baseline) and during a follow-up visit in a median
      of 210 days (range 87-857) after the first visit. Patients presenting 25(OH)D
      deficiency were advised to take cholecalciferol supplementation. RESULTS: At
      baseline, 60 (18%) patients had 25(OH)D deficiency (<=50 nmol/l, <=20 ng/l), and
      70 (21%) had insufficiency (50-74 nmol/l, 20-29 ng/l). Out of 121 patients with
      ongoing cholecalciferol supplementation at baseline, 25(OH)D deficiency and
      insufficiency was observed in 9 (7%) and 16 (13%) patients, respectively, whereas
      out of 52 patients with no supplementation, 15 (29%) had deficiency and 19 (37%)
      had insufficiency. Only 85 (26%) patients had optimal 25(OH)D levels (75-100
      nmol/l, 30-40 ng/l) at baseline. Seasonal variation was significant for 25(OH)D
      (p = 0.042) and 1,25(OH)2D (p = 0.001) levels. Living in a rural area was
      associated with a higher median 25(OH)D concentration as compared with living in
      an urban area (87 nmol/l, range 16-216 vs 72 nmol/l, range 17-162; p = 0.001).
      Regular sporting activity was positively associated with 25(OH)D (p = 0.045).
      Body mass index was inversely related to both 25(OH)D and 1,25(OH)2D (Spearman's
      rho = -0.24, p <0.001; rho = -0.23, p <0.001, respectively). The levels of
      25(OH)D and 1,25(OH)2D were correlated (rho = 0.21, p <0.001). Age and bone
      mineral density had no significant correlation with the levels of 25(OH)D. Follow
      up 25(OH)D was available for 230 patients, 44 (19%) of whom had 25(OH)D
      deficiency and 47 (21%) had insufficiency; 25 (41.6%) initially 25(OH)D-deficient
      patients attained sufficient 25(OH)D levels, whereas 33 (16.5%) patients with
      sufficient baseline 25(OH)D levels became deficient. Only 67 (30%) patients
      presented optimal 25(OH)D at the follow-up. CONCLUSION: A remarkable fraction of
      the patients had serum 25(OH)D below (40%) or above (30%) optimal levels, and
      only around 30% of patients had optimal levels. Levels of 25(OH)D and 1,25(OH)2D
      increased on cholecalciferol supplementation, but the usual supplementation
      regimens were not adequate to bring 25(OH)D to the optimal range for a large
      proportion of patients. TRIAL REGISTRATION NUMBER: EKSG 08/082/2B.

PMID- 29376549
TI  - Technical comment on: Guller et al. Lower hospital volume is associated with
      higher mortality after oesophageal, gastric, pancreatic and rectal cancer
      resection.

PMID- 29376550
TI  - Preventing HIV transmission through blockade of CCR5: rationale, progress and
      perspectives.
AB  - Of the two million people estimated to be newly infected with human
      immunodeficiency virus (HIV) every year, 95% live in poorer regions of the world
      where effective HIV treatment is not universally available. Strategies to reduce
      the spread of HIV infection, which predominantly occurs via sexual contact, are
      urgently required. In the absence of an effective vaccine, a number of approaches
      to prevent HIV infection have been developed. These include using potent anti-HIV
      drugs prophylactically, either through systemic administration or topical
      application to the mucosal tissues that HIV initially encounters during sexual
      transmission. Genetic deficiency of the chemokine receptor CCR5 provides
      individuals with a remarkable degree of protection from HIV acquisition. This is
      because CCR5 is the major coreceptor used by HIV to infect new target cells.
      Since CCR5 deficiency does not appear to carry any health disadvantages,
      targeting the receptor is a promising strategy for both therapy and prevention of
      HIV. In this review we first describe the advantages and limitations of the
      currently available strategies for HIV prevention, then we focus on strategies
      targeting CCR5, covering the progress that has been made in developing different
      classes of CCR5 inhibitors for prophylaxis, and the perspectives for their future
      development as new weapons in the global fight against HIV/AIDS.

PMID- 29376551
TI  - Availability and accessibility of perinatal data for the Robson classification of
      caesarean sections in Switzerland.

PMID- 29376552
TI  - Impact of a fracture liaison service on patient management after an osteoporotic
      fracture: the CHUV FLS.
AB  - In 2008, the Centre Hospitalier Universitaire Vaudois (CHUV, Lausanne,
      Switzerland) initiated a Fracture Liaison Service (FLS). All patients
      hospitalised for a low trauma fracture are identified by the FLS. Inpatients then
      choose to be managed by either the FLS team or their general practitioner (GP).
      In this study we compared the management between the FLS team and the GP in terms
      of diagnosis of osteoporosis, treatment, refracture rates and mortality after FLS
      recording. Results are compared with the management of osteoporosis before the
      creation of the FLS, as reported in the survey study Osteocare. A total of 606
      patients were included (80% women); 55% chose management by the FLS and 45% their
      GP. The mean age was 78.5, and hip was the main fracture site (44%). The
      percentage of patients having dual X-ray absorptiometry to diagnose osteoporosis
      was significantly higher in the FLS group than the GP group (72 vs 26.5%, p
      <0.01). This percentage was 31.4% in the Osteocare study. Overall, 50.3% of
      patients in the FLS group had osteoporosis versus 57.5% in the GP group (p
      <0.05). This percentage was 46.0% in the Osteocare study. Use of osteoporosis
      medication was higher in the FLS group (FLS 100% of the patients, GP 44.1%, p
      <0.001) and had increased since the Osteocare study (21.6%). One-year
      nonvertebral refracture rate was higher in GP group than in the FLS patients (5.1
      vs 3.0%, p <0.05), whereas more vertebral fractures were identified in the FLS
      group, owing to protocol-driven regular clinical and vertebral fracture
      assessment (VFA) evaluations (number of evaluations 8 vs 0, p <0.01). Unadjusted
      mortality was higher in GP group than in the FLS group at one and five years
      (6.93 vs 2.11% and 33.58 vs. 15.96%, p <0.04). After adjustment by age and
      fracture site, these results were not significant. With FLS management, diagnosis
      and treatment of osteoporosis were more frequent than with GP management; new
      nonvertebral fractures were less frequent. Moreover, both forms of management had
      increased relative to rates reported in a 2004-2006 nationwide survey Osteocare,
      before FLS creation.

PMID- 29376553
TI  - Do late preterm twins face an increased neonatal morbidity compared with
      singletons?
AB  - OBJECTIVE: Late preterm infants (born between 34 0/7 and 36 6/7 weeks of
      gestation) have been shown to have a higher morbidity and mortality than term
      infants. Furthermore, twins, both term and preterm, have a higher neonatal
      morbidity than singletons. The aim of our study was to examine if late preterm
      twins consequently have twice the neonatal morbidity when both risk factors
      prematurity and multiple pregnancy are present. STUDY DESIGN: A retrospective
      single-centre study was conducted to compare neonatal outcome of late preterm
      singletons and late preterm twins born between 34 0/7 and 36 6/7 weeks of
      gestation as well as term twins with a gestational age from 37 0/7 to 41 6/7
      weeks. Primary outcome was length of hospitalisation. Secondary outcome was
      neonatal morbidity. RESULTS: A total of 845 infants were included. Late preterm
      twins (n = 243) were hospitalised significantly longer than term twins (n = 107)
      (13.5 +/- 8.0 vs 6.29 +/- 2.0 days, p <0.001) and late preterm singletons (n =
      495) (13.5 +/- 8.0 vs 12.6 +/- 8.6 days, p = 0.011). Hyperbilirubinaemia occurred
      significantly more often in late preterm singletons than in late preterm twins
      (49.7 vs 29.2%; p<0.001). Otherwise, no significant differences were detected
      regarding neonatal morbidities or mortality of late preterm singletons and late
      preterm twins. Late preterm twins had a significantly higher incidence of most
      morbidities than term twins. CONCLUSION: Late preterm twins are hospitalised
      significantly longer than similar-aged singletons, but have otherwise similar
      neonatal morbidities. Hyperbilirubinaemia is less frequent in late preterm twins
      than late preterm singletons.

PMID- 29376554
TI  - Evaluation of the frequency of adrenal crises and preventive measures in patients
      with primary and secondary adrenal insufficiency in Switzerland.
AB  - AIMS OF THE STUDY: Adrenal insufficiency is a dangerous clinical condition,
      leading to significant morbidity or mortality in situations with inadequate
      glucocorticoid replacement treatment. We aimed to assess preventive measures in
      adrenal insufficiency and the incidence and risk factors of adrenal crisis, as
      well as to test the patients' knowledge about their disease. METHODS: All
      patients in May and June 2016 and December 2016 and January 2017 with primary
      (17.9%) or secondary (82.1%) adrenal insufficiency were prospectively included in
      this observational study. They completed questionnaires about their personal and
      medical background, including the occurrence of adrenal crises, and possession of
      an emergency card and medication. They were asked about self-perceived subjective
      knowledge of their disease and filled out two multiple-choice tests about the
      modalities of the glucocorticoid replacement therapy (test A) and dose adaptation
      in hypothetical clinical situations (test B) in order to objectively test their
      knowledge. RESULTS: A total of 56 datasets were available for descriptive and
      statistical analysis. Overall, 94.6% of the patients were equipped with an
      emergency card, 64.3% had their daily hydrocortisone with them and 57.1% carried
      spare hydrocortisone pills. Twelve patients had experienced at least one adrenal
      crisis. There were 4.4 adrenal crises per 100 disease-years. Precipitating causes
      for adrenal crises were mainly gastroenteritis, influenza and noncompliance.
      Globally, the patients' self-perceived, subjective knowledge level was good to
      very good. In the two objective knowledge tests, however, only 28.9% (test A) and
      60.1% (test B) of the questions were answered correctly. Secondary adrenal
      insufficiency reduced the chance of being in the group with better knowledge in
      test A. CONCLUSIONS: The incidence of adrenal crisis in Switzerland is lower than
      described in recent European studies. Although nearly all of the patients carry
      their emergency cards with them, emergency treatment is available in only about
      half of the patients. There is a mismatch between subjective and objective
      knowledge of the disease and the education of patients with adrenal insufficiency
      needs to be improved.

PMID- 29376555
TI  - Reply to technical comment on: Guller et al. Lower hospital volume is associated
      with higher mortality after oesophageal, gastric, pancreatic and rectal cancer
      resection.

PMID- 29376556
TI  - Computed tomography imaging for the characterisation of drugs with radiation
      density measurements and HU spectroscopy.
AB  - AIMS OF THE STUDY: To investigate the computed tomography (CT) density of
      frequently administered medications (1) for the better characterisation of
      substances on abdominal CT, (2) to allow radiologists to narrow down
      possibilities in the identification of hyperdense material in the bowel and (3)
      to provide forensic doctors with a tool to identify gastric contents before an
      autopsy. MATERIAL AND METHODS: From the list of the local hospital pharmacy, the
      50 most frequently used medications were identified and scanned twice with a 128
      row CT scanner (Acquillion, Toshiba, Tokyo, Japan). The protocol comprised two
      tube voltages of 100 kVp and 120 kVp, with a tube current of 100 mAs, a
      collimation of 0.5 mm and a slice thickness of 0.5 mm. Two readers were asked to
      measure the density (in Hounsfield units) and the noise (standard deviation of
      the Hounsfield units) of each pill in the two scans (100/120 kVp). After 4 weeks,
      both readers repeated the measurements to test repeatability (intra-rater
      agreement). The behaviour of each pill in hydrochloric acid (pH 2) was examined
      and the dissolution time was determined. RESULTS: The most dense pill was
      Cordarone (7265 HU), and the least was Perenterol (?529 HU), with an attenuation
      that was lower than fat density (<?120 HU). The standard deviation of pixel
      density (noise) reflects inhomogeneity of the pharmacological product, varying
      from 9 to 1592 HU among the different pills (at 120 kVp). The absolute average HU
      increase per pill when changing to lower voltage was 78 +/- 253 HU, with a linear
      fitting line with a slope of 0.21 as a constant variable in the density
      spectroscopy. After 4 hours in hydrochloric acid, only six tablets were still
      intact, including Flagyl and Dafalgan. The intra- and inter-rater agreements for
      all measurements were nearly perfect, with a correlation coefficient r of >=0.99
      (p <0.0001). CONCLUSION: Our data suggest that measuring the attenuation of drugs
      on CT images, including the homogeneity, and applying CT spectroscopy can narrow
      down possible identities of the most frequently medications. Other clinicians and
      forensic pathologists can perform this easy measurement, as the intra- and inter
      reader variability is very small.

PMID- 29376557
TI  - Excellent outcome of direct antiviral treatment for chronic hepatitis C in
      Switzerland.
AB  - BACKGROUND: The introduction of direct acting antivirals (DAAs) for the therapy
      of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm
      shift in the approach to this disease, rendering interferon-based therapies
      obsolete. AIMS OF THE STUDY: We retrospectively and prospectively evaluated
      treatment results after the introduction of DAA in Switzerland in a cohort of
      patients with CHC. METHODS: We examined 565 patients who received DAA treatment
      for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis
      stadium, treatment and outcome. In addition, outcome of re-treatment and
      resistance-associated substitutions (RAS) in patients that did not achieve
      sustained virological response (SVR) were evaluated. The majority of patients
      participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an
      intention-to-treat and a modified intention-to-treat analysis. RESULTS: Overall
      SVR rate for all patients was 94% (530 of 565, 95% CI 92-96%). Of 350 patients
      with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335
      of 350, 95% CI 94-98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of
      51, 95% CI 87-100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107,
      95% CI 87-97%). In patients with HCV genotype 4, the SVR rate was substantially
      lower at 85% (49 of 57, 95% CI 76-94%). The rate of advanced liver fibrosis
      (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan(r) in the entire
      patient population was 71% (404 of 565). Out of 35 patients that did not achieve
      SVR after DAA treatment, 32 had a relapse and 3 patients showed viral
      breakthrough. In 17 of 35 cases (49%) patients were treatment naive and 21 of 35
      patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14
      patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of
      the virus genome. Twenty-seven percent of patients who experienced treatment
      failure were not treated with recommended regimens as a result of drug
      availability and reimbursement limitations. CONCLUSION: In Switzerland, novel DAA
      treatments for CHC reflect the positive results from registration trials.
      Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016.
      Patients who experienced a relapse after DAA treatment in Switzerland
      predominantly showed mutations in the NS5A region of the virus genome. DAA
      treatment limitations in Switzerland did prevent optimal treatment regimens in
      some patients.

PMID- 29376558
TI  - Funding characteristics of randomised clinical trials supported by the Swiss
      National Science Foundation: a retrospective cohort study.
AB  - AIMS OF THE STUDY: Failure to publish publicly funded research represents a waste
      of scarce research resources across medical disciplines and countries. In
      Switzerland, about 40% of randomised clinical trials (RCTs) supported by the
      Swiss National Science Foundation (SNSF) were not published. We aimed to describe
      funding characteristics of published and unpublished RCTs supported by the SNSF,
      to quantify the amount of money spent for unpublished studies, and to compare our
      results to a similar study performed in the UK. METHODS: We established a
      retrospective cohort of RCTs funded by the SNSF up to 2015. For each RCT
      proposal, two investigators independently identified corresponding publications
      in electronic databases and trial registries. Teams of two investigators
      independently extracted details from the original SNSF proposal and, if
      available, from trial registries or publications. In addition, we surveyed
      principal investigators about trial costs and additional sources of funding.
      RESULTS: We included 101 RCTs supported by the SNSF between 1986 and 2015. Most
      were single-centre RCTs with a median of 138 participants (interquartile range
      [IQR] 76-400). Overall, 67 (67%) principal investigators responded to our main
      survey questions. Median total costs per RCT were CHF 428 000 (IQR 282 000-900
      000) of which the SNSF provided a median CHF 222 000 (67% of total costs, IQR 40
      80%). Most investigators (70%) mentioned additional funding, mainly from their
      own institution or private foundations. A total of CHF 6.7 million was granted to
      RCTs that remained unpublished. Funding characteristics were similar to publicly
      funded trials in the UK. CONCLUSIONS: A third of the total SNSF grant sum spent
      on healthcare RCTs between 1986 and 2015 did not result in peer-reviewed
      scientific publications. New SNSF grant schemes might improve publication
      outcomes but their effectiveness needs to be evaluated.

PMID- 29376559
TI  - Physical activity for women with breast cancer after adjuvant therapy.
AB  - BACKGROUND: Women with a diagnosis of breast cancer may experience short- and
      long-term disease and treatment-related adverse physiological and psychosocial
      outcomes. These outcomes can negatively impact prognosis, health-related quality
      of life (HRQoL), and psychosocial and physical function. Physical activity may
      help to improve prognosis and may alleviate the adverse effects of adjuvant
      therapy. OBJECTIVES: To assess effects of physical activity interventions after
      adjuvant therapy for women with breast cancer. SEARCH METHODS: We searched the
      Cochrane Breast Cancer Group (CBCG) Specialised Registry, the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), the Physiotherapy Evidence
      Database (PEDro), SPORTDiscus, PsycINFO, ClinicalTrials.gov, and the World Health
      Organization (WHO) International Clinical Trials Registry Platform, on 18
      September 2015. We also searched OpenGrey and Healthcare Management Information
      Consortium databases. SELECTION CRITERIA: We searched for randomised and quasi
      randomised trials comparing physical activity interventions versus control (e.g.
      usual or standard care, no physical activity, no exercise, attention control,
      placebo) after adjuvant therapy (i.e. after completion of chemotherapy and/or
      radiation therapy, but not hormone therapy) in women with breast cancer. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected studies,
      assessed risk of bias, and extracted data. We contacted trial authors to ask for
      additional information when needed. We calculated an overall effect size with 95%
      confidence intervals (CIs) for each outcome and used GRADE to assess the quality
      of evidence for the most important outcomes. MAIN RESULTS: We included 63 trials
      that randomised 5761 women to a physical activity intervention (n = 3239) or to a
      control (n = 2524). The duration of interventions ranged from 4 to 24 months,
      with most lasting 8 or 12 weeks (37 studies). Twenty-eight studies included
      aerobic exercise only, 21 involved aerobic exercise and resistance training, and
      seven used resistance training only. Thirty studies described the comparison
      group as usual or standard care, no intervention, or control. One-fifth of
      studies reported at least 20% intervention attrition and the average physical
      activity adherence was approximately 77%.No data were available on effects of
      physical activity on breast cancer-related and all-cause mortality, or on breast
      cancer recurrence. Analysis of immediately postintervention follow-up values and
      change from baseline to end of intervention scores revealed that physical
      activity interventions resulted in significant small-to-moderate improvements in
      HRQoL (standardised mean difference (SMD) 0.39, 95% CI 0.21 to 0.57, 22 studies,
      1996 women; SMD 0.78, 95% CI 0.39 to 1.17, 14 studies, 1459 women, respectively;
      low-quality evidence), emotional function (SMD 0.21, 95% CI 0.10 to 0.32, 26
      studies, 2102 women, moderate-quality evidence; SMD 0.31, 95% CI 0.09 to 0.53, 15
      studies, 1579 women, respectively; low-quality evidence), perceived physical
      function (SMD 0.33, 95% CI 0.18 to 0.49, 25 studies, 2129 women; SMD 0.60, 95% CI
      0.23 to 0.97, 13 studies, 1433 women, respectively; moderate-quality evidence),
      anxiety (SMD -0.57, 95% CI -0.95 to -0.19, 7 studies, 326 women; SMD -0.37, 95%
      CI -0.63 to -0.12, 4 studies, 235 women, respectively; low-quality evidence), and
      cardiorespiratory fitness (SMD 0.44, 95% CI 0.30 to 0.58, 23 studies, 1265 women,
      moderate-quality evidence; SMD 0.83, 95% CI 0.40 to 1.27, 9 studies, 863 women,
      respectively; very low-quality evidence).Investigators reported few minor adverse
      events.Small improvements in physical activity interventions were sustained for
      three months or longer postintervention in fatigue (SMD -0.43, 95% CI -0.60 to 
      0.26; SMD -0.47, 95% CI -0.84 to -0.11, respectively), cardiorespiratory fitness
      (SMD 0.36, 95% CI 0.03 to 0.69; SMD 0.42, 95% CI 0.05 to 0.79, respectively), and
      self-reported physical activity (SMD 0.44, 95% CI 0.17 to 0.72; SMD 0.51, 95% CI
      0.08 to 0.93, respectively) for both follow-up values and change from baseline
      scores.However, evidence of heterogeneity across trials was due to variation in
      intervention components (i.e. mode, frequency, intensity, duration of
      intervention and sessions) and measures used to assess outcomes. All trials
      reviewed were at high risk of performance bias, and most were also at high risk
      of detection, attrition, and selection bias. In light of the aforementioned
      issues, we determined that the evidence was of very low, low, or moderate
      quality. AUTHORS' CONCLUSIONS: No conclusions regarding breast cancer-related and
      all-cause mortality or breast cancer recurrence were possible. However, physical
      activity interventions may have small-to-moderate beneficial effects on HRQoL,
      and on emotional or perceived physical and social function, anxiety,
      cardiorespiratory fitness, and self-reported and objectively measured physical
      activity. The positive results reported in the current review must be interpreted
      cautiously owing to very low-to-moderate quality of evidence, heterogeneity of
      interventions and outcome measures, imprecision of some estimates, and risk of
      bias in many trials. Future studies with low risk of bias are required to
      determine the optimal combination of physical activity modes, frequencies,
      intensities, and durations needed to improve specific outcomes among women who
      have undergone adjuvant therapy.

PMID- 29376562
TI  - Cdk5.

PMID- 29376560
TI  - Inotropic agents and vasodilator strategies for the treatment of cardiogenic
      shock or low cardiac output syndrome.
AB  - BACKGROUND: Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) as
      complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac
      surgery are life-threatening conditions. While there is a broad body of evidence
      for the treatment of people with acute coronary syndrome under stable
      haemodynamic conditions, the treatment strategies for people who become
      haemodynamically unstable or develop CS remain less clear. We have therefore
      summarised here the evidence on the treatment of people with CS or LCOS with
      different inotropic agents and vasodilative drugs. This is the first update of a
      Cochrane review originally published in 2014. OBJECTIVES: To assess efficacy and
      safety of cardiac care with positive inotropic agents and vasodilator strategies
      in people with CS or LCOS due to AMI, HF or cardiac surgery. SEARCH METHODS: We
      searched CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in June 2017. We also
      searched four registers of ongoing trials and scanned reference lists and
      contacted experts in the field to obtain further information. No language
      restrictions were applied. SELECTION CRITERIA: Randomised controlled trials in
      people with myocardial infarction, heart failure or cardiac surgery complicated
      by cardiogenic shock or LCOS. DATA COLLECTION AND ANALYSIS: We used standard
      methodological procedures expected by Cochrane. MAIN RESULTS: We identified 13
      eligible studies with 2001 participants (mean or median age range 58 to 73 years)
      and two ongoing studies. We categorised studies into eight comparisons, all
      against cardiac care and additional other active drugs or placebo. These
      comparisons investigated the efficacy of levosimendan versus dobutamine,
      enoximone or placebo, epinephrine versus norepinephrine-dobutamine, amrinone
      versus dobutamine, dopexamine versus dopamine, enoximone versus dopamine and
      nitric oxide versus placebo.All trials were published in peer-reviewed journals,
      and analysis was done by the intention-to-treat (ITT) principle. Twelve of 13
      trials were small with few included participants. Acknowledgement of funding by
      the pharmaceutical industry or missing conflict of interest statements emerged in
      five of 13 trials. In general, confidence in the results of analysed studies was
      reduced due to serious study limitations, very serious imprecision or
      indirectness. Domains of concern, which show a high risk of more than 50%,
      include performance bias (blinding of participants and personnel) and bias
      affecting the quality of evidence on adverse events.Levosimendan may reduce short
      term mortality compared to a therapy with dobutamine (RR 0.60, 95% CI 0.37 to
      0.95; 6 studies; 1776 participants; low-quality evidence; NNT: 16 (patients with
      moderate risk), NNT: 5 (patients with CS)). This initial short-term survival
      benefit with levosimendan vs. dobutamine is not confirmed on long-term follow up.
      There is uncertainty (due to lack of statistical power) as to the effect of
      levosimendan compared to therapy with placebo (RR 0.48, 95% CI 0.12 to 1.94; 2
      studies; 55 participants, very low-quality evidence) or enoximone (RR 0.50, 95%
      CI 0.22 to 1.14; 1 study; 32 participants, very low-quality evidence).All
      comparisons comparing other positive inotropic, inodilative or vasodilative drugs
      presented uncertainty on their effect on short-term mortality with very low
      quality evidence and based on only one RCT. These single studies compared
      epinephrine with norepinephrine-dobutamine (RR 1.25, 95% CI 0.41 to 3.77; 30
      participants), amrinone with dobutamine (RR 0.33, 95% CI 0.04 to 2.85; 30
      participants), dopexamine with dopamine (no in-hospital deaths from 70
      participants), enoximone with dobutamine (two deaths from 40 participants) and
      nitric oxide with placebo (one death from three participants). AUTHORS'
      CONCLUSIONS: Apart from low quality of evidence data suggesting a short-term
      mortality benefit of levosimendan compared with dobutamine, at present there are
      no robust and convincing data to support a distinct inotropic or vasodilator drug
      based therapy as a superior solution to reduce mortality in haemodynamically
      unstable people with cardiogenic shock or LCOS.Considering the limited evidence
      derived from the present data due to a generally high risk of bias and
      imprecision, it should be emphasised that there remains a great need for large,
      well-designed randomised trials on this topic to close the gap between daily
      practice in critical care medicine and the available evidence. It seems to be
      useful to apply the concept of 'early goal-directed therapy' in cardiogenic shock
      and LCOS with early haemodynamic stabilisation within predefined timelines.
      Future clinical trials should therefore investigate whether such a therapeutic
      concept would influence survival rates much more than looking for the 'best' drug
      for haemodynamic support.

PMID- 29376566
TI  - Congenital heart defects in Williams syndrome.
AB  - Yuan SM. Congenital heart defects in Williams syndrome. Turk J Pediatr 2017; 59:
      225-232. Williams syndrome (WS), also known as Williams-Beuren syndrome, is a
      rare genetic disorder involving multiple systems including the circulatory
      system. However, the etiologies of the associated congenital heart defects in WS
      patients have not been sufficiently elucidated and represent therapeutic
      challenges. The typical congenital heart defects in WS were supravalvar aortic
      stenosis, pulmonary stenosis (both valvular and peripheral), aortic coarctation
      and mitral valvar prolapse. The atypical cardiovascular anomalies include
      tetralogy of Fallot, atrial septal defects, aortic and mitral valvular
      insufficiencies, bicuspid aortic valves, ventricular septal defects, total
      anomalous pulmonary venous return, double chambered right ventricle, Ebstein
      anomaly and arterial anomalies. Deletion of the elastin gene on chromosome
      7q11.23 leads to deficiency or abnormal deposition of elastin during
      cardiovascular development, thereby leading to widespread cardiovascular
      abnormalities in WS. In this article, the distribution, treatment and surgical
      outcomes of typical and atypical cardiac defects in WS are discussed.

PMID- 29376563
TI  - Physical activity, diet and other behavioural interventions for improving
      cognition and school achievement in children and adolescents with obesity or
      overweight.
AB  - BACKGROUND: The global prevalence of childhood and adolescent obesity is high.
      Lifestyle changes towards a healthy diet, increased physical activity and reduced
      sedentary activities are recommended to prevent and treat obesity. Evidence
      suggests that changing these health behaviours can benefit cognitive function and
      school achievement in children and adolescents in general. There are various
      theoretical mechanisms that suggest that children and adolescents with excessive
      body fat may benefit particularly from these interventions. OBJECTIVES: To assess
      whether lifestyle interventions (in the areas of diet, physical activity,
      sedentary behaviour and behavioural therapy) improve school achievement,
      cognitive function (e.g. executive functions) and/or future success in children
      and adolescents with obesity or overweight, compared with standard care, waiting
      list control, no treatment, or an attention placebo control group. SEARCH
      METHODS: In February 2017, we searched CENTRAL, MEDLINE and 15 other databases.
      We also searched two trials registries, reference lists, and handsearched one
      journal from inception. We also contacted researchers in the field to obtain
      unpublished data. SELECTION CRITERIA: We included randomised and quasi-randomised
      controlled trials (RCTs) of behavioural interventions for weight management in
      children and adolescents with obesity or overweight. We excluded studies in
      children and adolescents with medical conditions known to affect weight status,
      school achievement and cognitive function. We also excluded self- and parent
      reported outcomes. DATA COLLECTION AND ANALYSIS: Four review authors
      independently selected studies for inclusion. Two review authors extracted data,
      assessed quality and risks of bias, and evaluated the quality of the evidence
      using the GRADE approach. We contacted study authors to obtain additional
      information. We used standard methodological procedures expected by Cochrane.
      Where the same outcome was assessed across different intervention types, we
      reported standardised effect sizes for findings from single-study and multiple
      study analyses to allow comparison of intervention effects across intervention
      types. To ease interpretation of the effect size, we also reported the mean
      difference of effect sizes for single-study outcomes. MAIN RESULTS: We included
      18 studies (59 records) of 2384 children and adolescents with obesity or
      overweight. Eight studies delivered physical activity interventions, seven
      studies combined physical activity programmes with healthy lifestyle education,
      and three studies delivered dietary interventions. We included five RCTs and 13
      cluster-RCTs. The studies took place in 10 different countries. Two were carried
      out in children attending preschool, 11 were conducted in primary/elementary
      school-aged children, four studies were aimed at adolescents attending
      secondary/high school and one study included primary/elementary and
      secondary/high school-aged children. The number of studies included for each
      outcome was low, with up to only three studies per outcome. The quality of
      evidence ranged from high to very low and 17 studies had a high risk of bias for
      at least one item. None of the studies reported data on additional educational
      support needs and adverse events.Compared to standard practice, analyses of
      physical activity-only interventions suggested high-quality evidence for improved
      mean cognitive executive function scores. The mean difference (MD) was 5.00 scale
      points higher in an after-school exercise group compared to standard practice
      (95% confidence interval (CI) 0.68 to 9.32; scale mean 100, standard deviation
      15; 116 children, 1 study). There was no statistically significant beneficial
      effect in favour of the intervention for mathematics, reading, or inhibition
      control. The standardised mean difference (SMD) for mathematics was 0.49 (95% CI 
      0.04 to 1.01; 2 studies, 255 children, moderate-quality evidence) and for reading
      was 0.10 (95% CI -0.30 to 0.49; 2 studies, 308 children, moderate-quality
      evidence). The MD for inhibition control was -1.55 scale points (95% CI -5.85 to
      2.75; scale range 0 to 100; SMD -0.15, 95% CI -0.58 to 0.28; 1 study, 84
      children, very low-quality evidence). No data were available for average
      achievement across subjects taught at school.There was no evidence of a
      beneficial effect of physical activity interventions combined with healthy
      lifestyle education on average achievement across subjects taught at school,
      mathematics achievement, reading achievement or inhibition control. The MD for
      average achievement across subjects taught at school was 6.37 points lower in the
      intervention group compared to standard practice (95% CI -36.83 to 24.09; scale
      mean 500, scale SD 70; SMD -0.18, 95% CI -0.93 to 0.58; 1 study, 31 children, low
      quality evidence). The effect estimate for mathematics achievement was SMD 0.02
      (95% CI -0.19 to 0.22; 3 studies, 384 children, very low-quality evidence), for
      reading achievement SMD 0.00 (95% CI -0.24 to 0.24; 2 studies, 284 children, low
      quality evidence), and for inhibition control SMD -0.67 (95% CI -1.50 to 0.16; 2
      studies, 110 children, very low-quality evidence). No data were available for the
      effect of combined physical activity and healthy lifestyle education on cognitive
      executive functions.There was a moderate difference in the average achievement
      across subjects taught at school favouring interventions targeting the
      improvement of the school food environment compared to standard practice in
      adolescents with obesity (SMD 0.46, 95% CI 0.25 to 0.66; 2 studies, 382
      adolescents, low-quality evidence), but not with overweight. Replacing packed
      school lunch with a nutrient-rich diet in addition to nutrition education did not
      improve mathematics (MD -2.18, 95% CI -5.83 to 1.47; scale range 0 to 69; SMD 
      0.26, 95% CI -0.72 to 0.20; 1 study, 76 children, low-quality evidence) and
      reading achievement (MD 1.17, 95% CI -4.40 to 6.73; scale range 0 to 108; SMD
      0.13, 95% CI -0.35 to 0.61; 1 study, 67 children, low-quality evidence). AUTHORS'
      CONCLUSIONS: Despite the large number of childhood and adolescent obesity
      treatment trials, we were only able to partially assess the impact of obesity
      treatment interventions on school achievement and cognitive abilities. School and
      community-based physical activity interventions as part of an obesity prevention
      or treatment programme can benefit executive functions of children with obesity
      or overweight specifically. Similarly, school-based dietary interventions may
      benefit general school achievement in children with obesity. These findings might
      assist health and education practitioners to make decisions related to promoting
      physical activity and healthy eating in schools. Future obesity treatment and
      prevention studies in clinical, school and community settings should consider
      assessing academic and cognitive as well as physical outcomes.

PMID- 29376567
TI  - Cow's milk protein allergy awareness and practice among Turkish pediatricians: A
      questionnaire-survey.
AB  - Yuce A, Dalgic B, Cullu-Cokugras F, Cokugras H, Kansu A, Alptekin-Sarioglu A,
      Sekerel BE. Cow's milk protein allergy awareness and practice among Turkish
      pediatricians: A questionnaire-survey. Turk J Pediatr 2017; 59: 233-243. Region
      specific recommendations for the prevention, diagnosis, and treatment of cow's
      milk protein allergy (CMPA) are not available in Turkey. This cross-sectional
      questionnaire-survey was designed to evaluate CMPA awareness and practice among
      Turkish pediatricians. A total of 410 pediatricians were included based on their
      voluntary participation. Questionnaires elicited demographic data and
      pediatricians' awareness and practice of CMPA in infants and children. Atopic
      dermatitis (91.5%), diarrhea (88.0%) and significant blood in stool (85.9%) were
      the most common symptoms considered suggestive of CMPA. Continuation of breast
      feeding via elimination of CMP containing products from maternal diet was the
      most commonly selected (79.0%) therapeutic option in exclusively breast-fed
      infants diagnosed with CMPA. Amino acid-based formula was the most commonly
      selected formula in a non-exclusively breast-fed infant with CMPA, for infants
      presenting with anaphylaxis (58.8%), enterocolitis (40.7%) or multiple food
      allergies (52.0%), and also for at-risk infants (40.2%). Earliest time to re
      challenge was identified to be 6 months by 52.0% of pediatricians. In conclusion,
      our findings revealed high awareness of CMPA among Turkish pediatricians in terms
      of clinical presentation and first priority diagnostic tests. However, CMPA
      practice among Turkish pediatricians needs to be improved in terms of avoidance
      of other mammalian milks, selection of therapeutic formulas among non-exclusively
      breast-fed infants and at-risk infants consistent with guideline-based
      indications and cost-effectivity.

PMID- 29376568
TI  - Evaluation of Tissue Doppler Echocardiographic Imaging findings in children with
      pulmonary hypertension.
AB  - Akin A, Alehan D, Aykan HH, Ozkutlu S, Ozer S, Karagoz T. Evaluation of Tissue
      Doppler Echocardiographic Imaging findings in children with pulmonary
      hypertension. Turk J Pediatr 2017; 59: 244-253. Tissue Doppler Imaging has become
      an important prognostic marker that can be used in follow-up and determination of
      the prognosis in pulmonary hypertension patients. We compared the Tissue Doppler
      imaging parameters of 34 patients with pulmonary hypertension and 43 healthy
      controls. In addition, Brain-Natriuretic Peptide levels, pulmonary artery
      systolic pressures measured with echocardiography, 6-minute walking tests and New
      York Heart Association functional classification were compared. Among patients
      with Eisenmenger syndrome and idiopathic pulmonary hypertension, Tissue Doppler
      imaging parameters were mostly similar. In patients with New York Heart
      Association functional class 3, mitral septal annulus E/Ea (p=0.050) and mitral
      lateral annulus myocardial performance index (p=0.009) were higher than class 2
      patients. In patients with higher Brain Natriuretic Peptide level, mitral lateral
      annulus and tricuspid septal annulus Ea/Aa values were lower (p=0.046 and < 0.001
      respectively); tricuspid septal annulus E/Ea and interventricular septum
      myocardial performance index values were higher than in patients with normal
      Brain-Natriuretic Peptide level (p=0.006). In conclusion tissue Doppler imaging
      findings were significantly impaired in children with pulmonary hypertension
      compared to the control group. Findings were similar in patients with idiopathic
      pulmonary hypertension and Eisenmenger syndrome. Mitral lateral annulus
      myocardial performance index value may have a prognostic importance due its
      significant association with poor functional class. Due to the significant
      associations between mitral lateral annulus, tricuspid septal annulus Ea/Aa,
      tricuspid septal annulus Ea and E/Aa, interventricular septum-myocardial
      performance index values and brain natriuretic peptide levels, these parameters
      may be used in evaluating response to therapy.

PMID- 29376569
TI  - Clinical features and treatment results in children with hemangioma.
AB  - Atas E, Koc O, Artik HA. Clinical features and treatment results in children with
      hemangioma. Turk J Pediatr 2017; 59: 254-260. Hemangioma is a frequent disease
      which has a proliferative and involution phase. In this single center
      retrospective study, we evaluated clinical and therapeutic features of
      hemangiomas in children (n: 49). The median (range) age at onset and at admission
      were 21 days (10 days-156 months) and 7 months (0.25-192 months), respectively.
      The localization of lesions was: head region (n: 28; 57.2%), trunk (n: 8; 16.3%)
      trunk, limb (n: 8; 16.3%), and neck region (n: 5; 10.2%) neck region. Seventeen
      patients (34.7%) were treated. Following treatments were used: propranolol alone
      in 12 (24.5%) patients, steroid alone in 2 (4.1%) patients, prednisone plus
      propranolol in 2 (4.1%) patients, and propranolol plus surgery in 1 (2.0%)
      patient. The number of hemangioma (n > 1) (p = 0.026, OR = 9.5, 95% CI 1.3-69.2)
      and treatment other than observation (p = 0.008, OR = 10.5, 95% CI 1.8-59.1) were
      significant predictors in the univariate analysis; treatment other than
      observation was an independent predictor for clinical response (p = 0.014, OR =
      9.8, 95% CI 1.5-90.9).

PMID- 29376570
TI  - New prediction model for diagnosis of bacterial infection in febrile infants
      younger than 90 days.
AB  - Vujevic M, Benzon B, Markic J. New prediction model for diagnosis of bacterial
      infection in febrile infants younger than 90 days. Turk J Pediatr 2017; 59: 261
      268. Due to non-specific clinical presentation in febrile infants, extensive
      laboratory testing is often carried out to distinguish simple viral disease from
      serious bacterial infection (SBI). Objective of this study was to compare
      efficacy of different biomarkers in early diagnosis of SBI in infants < 90 days
      old. Also, we developed prediction models with whom it will be possible to
      diagnose SBI with more accuracy than with any biomarkers independently. Febrile <
      90-day-old infants hospitalized in 2-year-period at Department of Pediatrics,
      University Hospital Centre Split with suspicion of having SBI were included in
      this study. Retrospective cohort analysis of data acquired from medical records
      was performed. Out of 181 enrolled patients, SBI was confirmed in 70. Most common
      diagnosis was urinary tract infection (68.6%), followed by pneumonia (12.9%),
      sepsis (11.4%), gastroenterocolitis (5.7%) and meningitis (1.4%). Male gender was
      shown to be a risk factor for SBI in this population (p=0.008). White blood cell
      count (WBC), absolute neutrophil count (ANC) and C-reactive protein (CRP) were
      confirmed as the independent predictors of SBI, with CRP as the best one. Two
      prediction models built by combining biomarkers and clinical variables were
      selected as optimal with sensitivities of 74.3% and 75.7%, and specificities of
      88.3% and 86%. Evidently, CRP is a more superior biomarker in diagnostics of SBI
      comparing to WBC and ANC. Prediction models were shown to be better in predicting
      SBI than independent biomarkers. Although both showed high sensitivity and
      specificity, their true strength should be determined using validation cohort.

PMID- 29376571
TI  - Establishment of normative data for stretched penile length in Turkish preterm
      and term newborns.
AB  - Halil H, Oguz SS. Establishment of normative data for stretched penile length in
      Turkish preterm and term newborns. Turk J Pediatr 2017; 59: 269-273. The aim of
      this study was to establish a normal range of preterm and term stretched penile
      length based on their gestational age and anthropometric parameters at birth. A
      total of 585 infants; 336 (57.43%) preterm and 249 (42.57%) term male infants
      born between August 2015 and September 2016 with gestational age between 26 and
      41 weeks were included in our study. Stretched penile length was measured from
      the pubic ramus to the tip of the glans. Gestational age, stretched penile length
      and anthropometric parameters at birth (weight, length and head circumference)
      were recorded within the first three days of life. Variations of stretched penile
      length in relation to gestational age and anthropometric parameters were
      evaluated using multiple linear regression models. The mean stretched penile
      length +/- SD of preterm and term neonates were 2.5+/-0.565 cm and 3.2+/-0.551cm,
      respectively. In all infants, stretched penile length was significantly affected
      by gestational age and birth length (OR: 0.079, 95% CI 0.059-0.098, p=0.0001,
      OR:0.022, 95% CI 0.007-0.037, p=0.005, respectively). In term infants, stretched
      penile length was significantly affected by gestational age (OR: 0.139, 95% CI
      0.082-0.196, p=0.0001) and in preterm infants, gestational age and birth length
      significantly infleuenced the stretched penile length (OR: 0.090, 95% CI 0.065
      0.0115, p=0.0001, OR:0.024, 95% CI 0.009-0.039, p=0.002, respectively). This
      study provides reference values of stretched penile length for term and viable
      preterm Turkish infants.

PMID- 29376572
TI  - Does having an asthmatic sibling affect the quality of life in children?
AB  - Yilmaz O, Turkeli A, Karaca O, Yuksel H. Does having an asthmatic sibling affect
      the quality of life in children? Turk J Pediatr 2017; 59: 274-280. Chronic
      illness in a family member leads to deterioration of quality of life in other
      members of that family. We aimed to investigate the influence of having an
      asthmatic sibling on a child's quality of life (QoL). We enrolled 2-12 year aged
      healthy children with an asthmatic sibling in the study group and healthy
      children with a healthy sibling in the control group of this cross-sectional
      study. Sociodemographic characteristics of children and disease severity
      characteristics of asthmatic siblings were recorded. All parents filled in
      Turkish generic PedsQLTM short form appropriate for the child's age group. Study
      and control groups had 114 children each. Total PedsQLTM scores were not
      significantly different in any of the age groups (p=0.23, p=0.13, p= 0.11
      respectively). Emotional PedsQLTM sub-scores in children with an asthmatic
      sibling were significantly worse (83.0+/-16.5 vs 91.6+/-10.9 in the 2-4 year age
      group, 72.0+/-17.8 vs 92.2+/-11.6 in the 5-7 year age group, 73.7+/-24.1 vs
      88.7+/-14.8 in the 8-12 year age group respectively, p<=0.002 for all).
      Similarly, psychosocial sub-score was significantly lower in the 2-4 and 5-7-year
      olds but not the 8-12 year old groups (p=0.01, p=0.01, p=0.08 respectively). In
      conclusion, healthy children with asthmatic siblings have significantly lower
      emotional QoL and this needs to investigated for other chronic diseases in
      further research.

PMID- 29376573
TI  - Are cytokines and cortisol important predictors for the severity of pediatric
      croup: A case control study.
AB  - Uzum O, Caglar A, Kume T, Sayiner A, Er A, Akgul F, Ulusoy E, Yilmaz D, Duman M.
      Are cytokines and cortisol important predictors for the severity of pediatric
      croup: A case control study. Turk J Pediatr 2017; 59: 281-287. The aim of this
      study is to investigate the role of cytokines (TNF-alpha, IL-6, IL-10, and PAF),
      cortisol, and IgE in the pathogenesis of croup and the factors determining its
      clinical severity. Patients diagnosed with croup at the Pediatric Emergency
      Department were included and thirty healthy children were included as a control
      group. Patients' demographic characteristics, clinical findings, recurrent croup
      history, and patient-family atopy history were recorded. Patients were grouped
      according to the Westley croup scoring system. Blood samples were taken from the
      control group and the patients for cytokines and cortisol. Respiratory pathogens
      were studied with PCR. Sixty-nine pediatric cases who were diagnosed as croup
      were included in the study (34 mild, 31 moderate, 4 severe). Group comparisons
      were made in terms of mild and moderate/severe groups. In the moderate/severe
      group, IL-10 and cortisol levels were higher than the mild group. The
      moderate/severe cortisol levels between 12:00 am-6:00 pm were found to be higher.
      PAF and TNF-alpha levels were detected to be higher in patients with a history of
      atopy. Viral agents were isolated in 45 patients; rhinovirus PCR tests were
      positive in 22 patients. In this study, rhinovirus was the most common etiology
      for croup. Increased levels of IL-10 and cortisol in the moderate/severe group
      indicate that different systemic and local mechanisms may play a role in the
      pathogenesis of croup.

PMID- 29376574
TI  - The behavior pattern of parents of patients with subacute sclerosing
      panencephalitis concerning alternative medicine.
AB  - Isikay S. The behavior pattern of parents of patients with subacute sclerosing
      panencephalitis concerning alternative medicine. Turk J Pediatr 2017; 59: 288
      294. The aim of the study was to examine the attitude of the parents of Subacute
      Sclerosing Panencephalitis (SSPE) patients regarding alternative treatment
      methods and compare with those of the parents of epilepsy patients. The study
      comprised 39 SSPE and 53 epilepsy patients who were under follow-up in Gaziantep
      Children's Hospital. A questionnaire designed to inquire about the knowledge (13
      questions) and behavior (11 questions) of parents about alternative medicine
      methods was given to the caregiver of all patients. The ratio of parents using
      alternative medicine methods was 29/39 (74.4%) in the SSPE group and 8/53 (15.1%)
      in the epilepsy group. Less than half of the parents of SSPE patients reported
      talking about it with their doctors. These results show parents facing a chronic
      debilitating disease frequently seek benefit from alternative methods. Most
      define this treatment as complementary to the established medical treatment.
      However, potential and unrecognized adverse events of alternative methods and
      their interference with regular medical treatment can be of importance,
      especially because treating physicians are seldom informed about concurrent use.

PMID- 29376575
TI  - Evaluation of the functional capacity, respiratory functions and musculoskeletal
      systems of the children with chest pain for non-cardiac reasons.
AB  - Daskapan A, Sanli C, Aydogan-Arslan S, Ciledag-Ozdemir F, Korkem D, Kara U.
      Evaluation of the functional capacity, respiratory functions and musculoskeletal
      systems of the children with chest pain for non-cardiac reasons. Turk J Pediatr
      2017; 59: 295-303. Chronic chest pain in healthy children and adolescents
      generally arises from non-cardiac factors. The purpose of our study was to
      compare the evaluation results of effort test, respiratory function and
      musculoskeletal system in children and adolescents with chest pain for non
      cardiac reasons with healthy children and adolescents. Physical activity level
      was determined by the International Physical Activity Questionnaire. The
      respiratory function test was performed using a spirometer. The posture analysis
      was performed to determine the upper body deformities. The effort test was
      performed on a treadmill. The two groups were similar in terms of the physical
      activity levels, respiratory function and effort test results (p > 0.05). The
      rate of the rounded shoulder, kyphosis was significantly higher in the patient
      group with chest pain (p < 0.005). Consequently, the musculoskeletal system
      findings including the pectoralis minor shortness, rounded shoulder, and thoracic
      kyphosis could have a role in non-cardiac chest pain.

PMID- 29376576
TI  - The high prevalence of inappropriate feeding among infants presenting with an
      apparent life-threatening event.
AB  - Kojima K, Mckinley K, Donohue P, Sigal Y. The high prevalence of inappropriate
      feeding among infants presenting with an apparent life-threatening event. Turk J
      Pediatr 2017; 59: 304-310. Although there are anecdotal reports of a link between
      inappropriate feeding and an apparent life-threatening event (ALTE), previous
      studies have not examined this association in a cohort of affected infants. This
      study compared the feeding behaviors of infants who have had an ALTE with age-
      and sex-matched controls. This is a single-center case control study. Forty-six
      term infants aged 6 months or less, who were hospitalized over a 34-month period
      following an ALTE, comprised the study sample; 92 age- and sex-matched controls
      were recruited from a wellness clinic. Feeding practices reported by parents were
      evaluated for their appropriateness with respect to the volume of each feeding,
      and the frequency and total volume of feedings per 24-hour period, based on the
      American Academy of Pediatrics guidelines. Comparisons were made between the ALTE
      cases and controls. Inappropriately fed infants were compared with the rest of
      the sample. The ALTE and control groups were similar with respect to the
      prevalence of breastfeeding, insurance, birth weight, and weight percentile at
      presentation. The ALTE group had a lower prevalence of appropriate feeding
      compared to the control group (43.5% versus 63.0%, p = 0.029). Overfed infants
      were at a higher weight percentile at the time of presentation (46.5th percentile
      versus 31.4 < sup > th < /sup > percentile, p = 0.037). These results represent
      the association between ALTE and inappropriate feeding practice, which emphasizes
      the need for assessment and education regarding feeding practices in patient
      presenting with an ALTE.

PMID- 29376577
TI  - p.Val452Ile mutation of the SLC25A13 gene in a Turkish patient with citrin
      deficiency.
AB  - Seker-Yilmaz B, Kor D, Tumgor G, Ceylaner S, Onenli-Mungan N. p.Val452Ile
      mutation of the SLC25A13 gene in a Turkish patient with citrin deficiency. Turk J
      Pediatr 2017; 59: 311-314. Citrin deficiency is an autosomal recessive metabolic
      disorder, which is caused by pathogenic mutations in the SLC25A13 gene on
      chromosome 7q21.3, as the causative gene that encodes the liver type
      aspartate/glutamate carrier isoform 2 (AGC2). One of the main clinical
      presentations is neonatal intrahepatic cholestatic hepatitis caused by citrin
      deficiency. We report a Turkish child presented with prolonged neonatal jaundice
      associated with elevated plasma citrulline and galactosuria. NICCD was suspected
      at this point and mutation study of SLC25A13 showed that she was homozygous for
      the missense NM_014251.2:c.1354G > A (NP_055066.1:p.Val452Ile) (dbSNP:
      rs143877538) mutation. Dramatic response was observed to the dietary treatment
      with medium-chain triglycerides containing formula, ursodeoxycholic acid and fat
      soluble vitamin supplementation. The minor allele frequency of this variant was
      given as nearly as 0.01 in the South Asian population; it seems like a disease
      causing variant. This is the first report of this variant in the Turkish and
      European population.

PMID- 29376578
TI  - An infant with glutaric aciduria type IIc diagnosed with a novel mutation.
AB  - Isikay S, Yaman A, Ceylaner S. An infant with glutaric aciduria type IIc
      diagnosed with a novel mutation. Turk J Pediatr 2017; 59: 315-317. Glutaric
      aciduria type II is a rare inborn error of metabolism. The clinical picture is
      highly variable with symptoms ranging from acute metabolic decompensations to
      chronic, mainly muscular problems or even asymptomatic cases. Herein we described
      a 7-month-old female patient presented with respiratory failure and diagnosed
      with glutaric aciduria type II via whole exome sequencing that exhibited one
      known and a novel mutation. Her blood and urine analyses were all normal. After
      the diagnosis, dramatic and sustained improvement on a low-fat, low-protein, and
      high-carbohydrate diet supplemented with oral riboflavin and carnitine was
      determined. In especially hypotonic patients with unknown etiologies, though the
      blood and urine analyses are normal, glutaric aciduria type II should also be
      kept in mind and genetic tests may be required for the diagnosis.

PMID- 29376579
TI  - Alpha coma in an adolescent with diabetic ketoacidosis.
AB  - Ostojic S, Vukovic R, Milenkovic T, Mitrovic K, Djuric M, Nikolic L. Alpha coma
      in an adolescent with diabetic ketoacidosis. Turk J Pediatr 2017; 59: 318-321.
      This is the first report of alpha coma (AC) caused by brain edema in a patient
      with diabetic ketoacidosis (DKA). A previously healthy 15-year-old girl was
      admitted to the intensive care unit due to altered state of consciousness during
      the course of treatment for DKA. Patient was in a coma, intubated and had
      tachycardia with poor peripheral perfusion. Results of laboratory analyses
      indicated severe DKA and computed tomography scan indicated diffuse brain edema.
      The EEG pattern showed uniform alpha activity. Treatment with intravenous fluids,
      insulin and mannitol was started. Patient's state of consciousness gradually
      improved and on the third day she was extubated. On the fifth day, her neurologic
      status and EEG findings were completely normal with no residual neurological
      deficits. In conclusion, although AC is associated with a high fatality rate,
      favorable outcome can be achieved with prompt recognition and treatment of
      cerebral edema in pediatric patients with DKA.

PMID- 29376580
TI  - Different presentations of cow's milk protein allergy during neonatal period.
AB  - Aktas S, Ergenekon E, Unal S, Turkyilmaz C, Hirfanoglu IM, Atalay Y. Different
      presentations of Cow's milk protein allergy during neonatal period. Turk J
      Pediatr 2017; 59: 322-328. Cow's milk protein allergy (CMPA) is the most common
      cause of allergy occurring in the first year of life due to infant formula or
      breast-milk of mothers who are drinking cow's milk or eating cow's milk products.
      Most children with allergic colitis are symptomatic in the first months, usually
      by 4 weeks. There are rare cases whom were sensitized prenatally and demonstrated
      symptoms in the first week, even in the first 2 days of life. The most common
      clinical sign of CMPA is bloody stool in a well-appearing infant. Gross bloody
      stool or fecal occult blood are also the common signs of necrotizing
      enterocolitis (NEC), especially in preterm infants with systemic instability. The
      treatment options are totally different so the clinician has to be very careful
      evaluating the patient. We report 5 preterm cases of CMPA, two of whom were
      siblings. Two of them presented with massive bloody stools and 3 of them
      presented with abdominal distension and fecal occult blood all of which were
      initially considered as NEC. Literature review of 20 cases with similar history
      is summarized as well.

PMID- 29376581
TI  - Hereditary spastic paraplegia type 35 caused by a novel FA2H mutation.
AB  - Bektas G, Yesil G, Yildiz EP, Aydinli N, Caliskan M, Ozmen M. Hereditary spastic
      paraplegia type 35 caused by a novel FA2H mutation. Turk J Pediatr 2017; 59: 329
      334. Hereditary spastic paraplegia type 35 (SPG35) is a rare disorder
      characterized by progressive spasticity. Mutations in the fatty acid 2
      hydroxylase (FA2H) gene in different loci are responsible for phenotypic
      variability. We aimed to define the phenotype of SPG35 linked to a novel
      homozygous mutation c.160_169dup (p.Asp57Glyfs*48) in the FA2H gene, and compared
      with the clinical characteristics and neuroimaging findings of the patients with
      mutation in the FA2H gene. We describe a 5-year-old boy presenting with spastic
      paraplegia. He developed a rapid progressive spastic paraplegia and loss of
      ambulation at an early age, despite the absence of accompanying seizure,
      neuropathy, cognitive impairment, speech disturbance, and optic atrophy.
      Neuroimaging revealed white matter changes without brain iron accumulation. A
      duplication variation; leading to a truncated protein c.160_169dup in the FA2H
      gene was found on the homozygous state. A homozygous mutation c.160_169dup in the
      FA2H gene, which resulted in SPG35 phenotype, may present with rapid progressive
      spastic paraplegia at an early age.

PMID- 29376582
TI  - A case report with sacral appendage: Is it accessory penis or human tail?
AB  - Kocaoglu C, Kocaoglu C, Akkoyun I, Karanis IE. A case report with sacral
      appendage: Is it accessory penis or human tail? Turk J Pediatr 2017; 59: 335-337.
      Lumbo-sacro-coccygeal appendages are very rare congenital anomalies. It is
      difficult to say that they are a evolutionary inheritance (tail) from our
      ancestors or an anomaly (pseudotail) occuring during embrional development. If it
      is a true tail, this lesion contains adipose and connective tissue, striated
      muscle, blood vessel and nerves, and is covered by skin. However, if this lesion
      is a pseudotail, it may be an anomalous prolongation of the coccygeal vertebra,
      lipoma, teratoma, condrodystrophy or parasitic fetus. We present an infant with a
      sacral appendage resembling a penis, and its clinical and pathologic differential
      diagnosis and management are discussed based on literature. Sacral appendages,
      such as asaccessory penis or human tail, are treated through simple surgical
      excision. However, patients must be carefully evaluated regarding teratoma and
      spinal cord pathology.

PMID- 29376583
TI  - Clinical implications of prenatal diagnosis of aorto-left ventricular tunnel on
      postnatal treatment and final outcome.
AB  - Kosutic J, Prijic S, Stajevic M, Kalaba M, Ninic S, Mikovic Z, Vujic A, Popovic
      S. Clinical implications of prenatal diagnosis of aorto-left ventricular tunnel
      on postnatal treatment and final outcome. Turk J Pediatr 2017; 59: 342-344. There
      are no more than 20 antenatally diagnosed aorto-left ventricular tunnel cases
      reported in the literature. In most of them the diagnosis was made indirectly and
      only after multiple fetal scans based on findings such as thick and dilated left
      ventricle and grossly dilated ascending aorta. We present a patient in whom a
      direct tunnel visualization and aorto-left ventricular tunnel diagnosis was made
      at the 30th gestation week after a single fetal scan using the recently
      introduced 'cockade sign'. Clinical implications of antenatal diagnosis on
      postnatal treatment and outcome are also discussed.

PMID- 29376584
TI  - Where did the salt go?
AB  - Paul SP, Hicks SS, Sanjeevaiah MK, Heaton PA. Where did the salt go? Turk J
      Pediatr 2017; 59: 345-348. Bronchiolitis is a self-limiting viral respiratory
      tract-infection seen commonly in infants. Some infants require hospitalization
      for feeding or respiratory support. A wide range of extra-pulmonary complications
      such as arrhythmias, myocarditis, central apneas, seizures, and hyponatremia are
      uncommonly known to occur with respiratory syncytial virus (RSV) infections. We
      present a 4-week-old-female infant admitted with RSV bronchiolitis for feeding
      support by nasogastric-tube. The infant suffered unexpected desaturations and
      seizure-like event 30-hours post-admission. Severe hyponatremia (sodium: 114
      mmol/L) was detected although cause for this remained unexplained initially.
      Serum sodium improved following a bolus of 2.7% hypertonic-saline. The infant
      subsequently needed advanced respiratory support. Around time of transfer to
      PICU, the infant developed abdominal distension and continued to have bilious
      aspirate even after 6-days. An upper gastrointestinal contrast-study confirmed
      malrotation; improved following surgery. Co-existence of two serious pathologies
      may have accounted for the hyponatremia: malrotation (possible source of sodium
      loss into third-space) and severe bronchiolitis (inappropriate ADH-secretion).
      This case highlights the importance of determining origin of hyponatremia
      associated with acute bronchiolitis.

PMID- 29376585
TI  - Occipital cortex dysgenesis with white matter changes due to mutations in Laminin
      a2.
AB  - Yis U, Dixit V, Isikay S, Karakaya M, Baydan F, Diniz G, Polat I, Hiz-Kurul S,
      Cirak S. Occipital cortex dysgenesis with white matter changes due to mutations
      in Laminin a2. Turk J Pediatr 2017; 59: 338-341. Laminin alpha2 related
      congenital muscular dystrophy is one of the most common congenital muscular
      dystrophies of childhood with or without clinical evidence of central nervous
      system involvement. It may be associated with significant white matter
      abnormalities resembling leukodystrophies. In this study, we elaborated on two
      cases with laminin alpha2 related congenital muscular dystrophy who had occipital
      cortex dysgenesis in addition to characteristic white matter abnormalities.
      Although laminin alpha2 related congenital muscular dystrophy with white matter
      abnormalities is known, the association with occipital cortex dysplasia has been
      not well recognized by clinical colleagues.

PMID- 29376586
TI  - Wickerhamomyces anomalus blood stream infection in a term newborn with pneumonia.
AB  - Yilmaz-Semerci S, Demirel G, Tastekin A. Wickerhamomyces anomalus blood stream
      infection in a term newborn with pneumonia. Turk J Pediatr 2017; 59: 349-351. The
      incidence of invasive candidiasis is high in neonates admitted to neonatal
      intensive care unit and is associated with significant morbidity and mortality
      rates. Candida albicans is the most common fungal agent pathogenic to neonates
      but invasive fungal infections caused by uncommon fungi have increased in recent
      years. Wickerhamomyces anomalus is a very rare pathogen causing blood stream
      infection in neonates, which has reportedly caused only few cases in the
      literature. Here we report a case of blood stream infection caused by a fungal
      agent Wickerhamomyces anomalus in a term male infant.

PMID- 29376587
TI  - Is autologous cord blood transfusion effective and safe in preterm infants?

PMID- 29376588
TI  - [Russian society of urology over the past 5 years].

PMID- 29376589
TI  - [Application of 3D soft print models of the kidney for treatment of patients with
      localized cancer of the kidney (a pilot study)].
AB  - AIM: To evaluate the possibility of using 3D-printing in the management of
      patients with localized kidney cancer. MATERIALS AND METHODS: The study comprised
      five patients with localized kidney cancer who were treated at the Urology Clinic
      of the I.M. Sechenov First Moscow State Medical University from January 2016 to
      April 2017. Along with the standard examination, the patients underwent
      multispiral computed tomography (MSCT) to produce patient-specific 3D-printed
      models of the kidney tumors using 3D modeling and 3D printing. To evaluate the
      effectiveness of using 3D-printed models, two-stage preoperative planning was
      conducted, and five surgeons were surveyed using a four-question multiple choice
      questionnaire. At the first stage, the planning of operations was carried out
      based on MSCT findings. At the second stage, the surgeons were given patient
      specific soft 3D models of the kidney with a tumor for preoperative training.
      After preoperative training, patients underwent laparoscopic resection of the
      kidney with a tumor. RESULTS: According to the survey results, each of the
      participating surgeons at least once changed surgical plan based on data obtained
      with 3D printed models of the kidney with the tumor. The implementation of
      preoperative training using 3D printed models of the kidney turned out to be
      effective. All patients underwent laparoscopic surgery performed by a single
      surgeon with extensive experience in this type of surgery. The mean operative
      time was 187 minutes. All operations were performed with main renal artery
      occlusion. The men warm ischemia time was 19.5 minutes and the mean blood loss
      was 170 ml. There were no conversions to open surgery and organ-removing
      operations. There were no postoperative complications or deaths. All surgical
      margins were negative. Morphological examination showed that four patients had
      renal cell carcinoma one patient had the oncocytoma. CONCLUSION: The study
      demonstrated the promise of using 3D printing for preoperative planning and
      surgical performance due to a high-precision three-dimensional soft patient
      specific model of the localized kidney.

PMID- 29376590
TI  - [Effects of the of renal warm ischemia time on the recovery of filtration
      function in the experiment].
AB  - AIM: To investigate experimentally ultrastructural and biochemical signs of acute
      injury to the renal parenchyma after warm renal ischemia of various duration and
      subsequent reperfusion. MATERIALS AND METHODS: The experiments were performed on
      44 healthy conventional female rabbits of the "Chinchilla" breed weighted 2.6-2.7
      kg, which were divided into four groups. In the first, control, group included
      pseudo-operated animals. In the remaining three groups, an experimental model of
      warm ischemia of renal tissue was created, followed by a 60-minute reperfusion.
      The renal warm ischemia time was 30, 60 and 90 minutes in the 2nd, 3rd and 4th
      groups, respectively. Electron microscopy was used to study ultrastructural
      disturbances of the renal parenchyma. Biochemical signs of acute kidney damage
      were detected by measuring the following blood serum and/or urine analytes: NGAL,
      cystatin C, KIM-1, L-FABP, interleukin-18. The glomerular filtration was
      evaluated by creatinine clearance, which was determined on days 1, 5, 7, 14, 21
      and 35 of follow-up. RESULTS: A 30-minute renal warm ischemia followed by a 60
      minute reperfusion induced swelling and edema of the brush membrane, vacuolation
      of the cytoplasm of the endothelial cells of the proximal tubules, and microvilli
      restructuring. The observed disorders were reversible, and the epithelial cells
      retained their viability. After 60 minutes of ischemia and 60 minutes of
      reperfusion, the observed changes in the ultrastructure of the epithelial cells
      were much more pronounced, some of the epithelial cells were in a state of
      apoptosis. 90 min of ischemia and 60 min of reperfusion resulted in electron
      microscopic signs of the mass cellular death of the tubular epithelium.
      Concentration in serum and/or biochemical urine markers of acute renal damage
      increased sharply after ischemic-reperfusion injury. Restoration of indicators
      was observed only in cases when the renal warm ischemia time did not exceed 60
      minutes. The decrease in creatinine clearance occurred in the first 24 hours
      after the intervention, lasting not less than two weeks after a 30-minute warm
      ischemia, at least 3 weeks after a 60-minute warm ischemia and continued more
      than a month after a 90-minute renal artery occlusion. CONCLUSION: Intraoperative
      warm ischemia and subsequent reperfusion are the actual reasons for the
      alteration of the ultrastructure of the renal tissue and the impairment of the
      filtration function. The severity of the disorders depends on the duration of the
      damaging factors. After a 30-60-minute ischemia, the structural and functional
      changes in the renal tissue are reversible. The mass death of nephrocytes
      effectors is possible only after warm renal ischemia longer than 60 min.

PMID- 29376591
TI  - [Association of polymorphism of 1800255 COL3A1 gene with pelvic organ prolapse
      and urinary incontinence in women: preliminary data].
AB  - RELEVANCE: Collagen type I and III have a significant role in the development of
      pelvic organ prolapse (POP) and urinary incontinence in women. The role of the
      COL3A1 gene polymorphism remains debatable. Some studies and meta-analyzes have
      found a direct correlation between genetic defects and POP, while other
      researchers have not confirmed this association. This study aimed to investigate
      the association of the 1800255 COL3A1 gene polymorphism with the development of
      POP and urinary incontinence in women. MATERIALS AND METHODS: The study group
      comprised 52 patients (mean age 64.4 years) with verified POP and stress urinary
      incontinence. The control group included 21 patients without pelvic floor
      dysfunction. Patients were comparable in age and had at least one or more risk
      factors for developing pelvic floor dysfunction. Exclusion criteria for both
      groups were Marfan and Ehlers-Danlos syndromes and a history of surgery for POP
      or incontinence (for the control group). In all women, saliva samples were
      collected to detect polymorphism at the rs1800255 locus of the COL3A1 gene.
      Genotyping was conducted by Sanger sequencing. RESULTS: In patients with isolated
      genital prolapse, homozygous polymorphism (AA) had a low sensitivity (0.06) but
      an extremely high specificity (0.95). Heterozygote (GA) had the sensitivity of
      0.35, the specificity of 0.53, and the AUC of 0.44. For urinary incontinence by
      homozygote (AA), sensitivity was 0.08, specificity 0.96, and by heterozygote (GA)
      0.45 and 0.63, respectively. For the combination of pelvic prolapse and urinary
      incontinence by homozygote (AA), sensitivity was 0.07, specificity 1.0, and
      heterozygote (GA) 0.41 and 0.62, respectively. CONCLUSION: Given the high
      specificity of the polymorphism at the rs1800255 locus of the COL3A1 gene,
      determined by the Sanger sequencing, it can be concluded that there is an
      association between this polymorphism and urinary incontinence and POP in women.

PMID- 29376592
TI  - [Is there screening for urinary tuberculosis?]
AB  - INTRODUCTION: Most of the patients with genitourinary tuberculosis are detected
      too late. One of the reasons for this is the lack of a simple, cheap, reliable
      screening. The purpose of this study was to investigate the possibility of using
      a recombinant tuberculosis allergen (diaskintest) as a screening test to detect
      patients with genitourinary tuberculosis. MATERIAL AND METHODS: This is a simple
      prospective, open-label cohort study comprising 197 patients admitted to the
      Novosibirsk Research Institute of Tuberculosis for differential diagnosis in 2014
      2016. Of then, 72 patients were found to have urogenital tuberculosis, while 125
      patients had chronic nonspecific infections. RESULTS: The sensitivity of the
      Kochs subcutaneous tuberculin test and the diaskintest was 80.4% and 63.8%,
      respectively. The specificity of the Kochs test was 91.5%, which makes it still
      possible to consider it essential in the differential diagnosis of urogenital
      tuberculosis and nonspecific urogenital infections. A high percentage of positive
      diaskintest results in patients with chronic infectious and inflammatory diseases
      of the genitourinary system caused a low specificity of the test - 37.5%.
      CONCLUSION: Diaskintest can be used in screening for genitourinary tuberculosis,
      but its positive result indicative for diagnosis. It may be used only as a reason
      for in-depth phthisiourological examination using additional provocative tests,
      in particular, Kochs test, which showed high diagnostic performance.

PMID- 29376593
TI  - [Association of polymorphism of GSTT1 and GSTM1 genes with infertility in men].
AB  - AIM: To identify the association between homozygous deletion genotypes of
      glutathione transferase genes GSTT1 (glutathione transferase theta 1), GSTM1
      (glutathione S-transferase mu1) and infertility in Russian men. MATERIALS AND
      METHODS: The article presents a comparative analysis of the incidence of
      homozygous deletion genotypes of glutathione transferase genes GSTM1 and GSTT1 in
      Russian men with and without infertility. The study group comprised 160 infertile
      Russian men of reproductive age (mean age 30.2+/-3.6 years.) The infertility
      diagnosis was verified according to the WHO guidelines. The control group
      comprised 104 healthy Russian volunteers (mean age 31.3+/-5.4 years.) Molecular
      genetic detection of GSTM1 and GSTT1 deletion polymorphisms was performed using
      PCR. The genomic DNA for the study was extracted from whole blood samples.
      RESULTS: The study and control group differed significantly in incidence of GSTM1
      (p=0.043) and GSTT1 (p=0.008) deletion polymorphisms. The probability of
      detecting "zero" genotypes of the GSTT1 and GSTM1 genes in infertile men was 2.5
      (p<0.05) and 1.7 times higher (p<0.05), respectively, than in fertile men.
      CONCLUSIONS: Therefore, the study findings allow us to conclude that the deletion
      genotypes of GSTM1 and GSTT1 are associated with infertility in Russian men.
      Molecular genetic analysis of deletion polymorphism of glutathione transferase
      genes can be recommended for a comprehensive examination of infertile men.

PMID- 29376594
TI  - [Clinical and biochemical aspects of pathogenesis of urolithiasis].
AB  - AIM: To investigate the role of infection in the pathogenesis of urolithiasis
      using chromatography mass spectrometry analysis. MATERIALS AND METHODS: The study
      analyzed clinical and laboratory data of 316 urolithiasis patients hospitalized
      between February 2005 and January 2015. All patients underwent a comprehensive
      clinical examination, including laboratory tests (hematological and biochemical
      blood tests, clinical and bacteriological tests of urine) and chromatography mass
      spectrometry analysis urine and blood. The laboratory testing was carried out
      both during the patients hospital stay and outpatient follow-up. RESULTS: We
      analyzed the biological material for the presence of characteristic ions. Urine
      samples of 316 urolithiasis patients were found to contain activators of
      "cooperative sensitivity." Moreover, there was a significant increase in the
      concentration of signaling compounds of the "cooperative sensitivity" of
      microorganisms in patients with complicated urolithiasis in comparison with the
      control indices (lactones-0.006 plus/minus 0.0004 mmol/L, normal values less than
      0.002, quinolones 0.004 plus/minus 0.0003 mmol/l, normal values - less than 0.002
      and furan esters - 0.005 plus/minus 0.0004, normal values less than 0.002).
      Threshold values of the activators of "cooperative sensitivity" demonstrated the
      readiness of the microbial community to initiate an inflammatory process. The
      presence of activators such as lactones, quinolones and furan esters in the
      samples of urolithiasis patients predisposes to the activation of pathogenic
      genes in a large group of microorganisms, including gram positive and gram
      negative species. DISCUSSION: In our opinion, to improve the quality of
      diagnostic, treatment and preventive measures in patients with different types of
      stone formation, it is advisable to use chromatography mass spectrometry
      analysis, which allows determination of priority clinical and laboratory
      indicators. CONCLUSION: The data on the role of infection in the pathogenesis of
      urolithiasis obtained by chromatographic methods suggest the possibility of using
      the indicators of the activators of the "cooperative sensitivity" of microbes in
      patients with various forms of urolithiasis to assess the disease severity.

PMID- 29376595
TI  - [Experimental work: reconstruction of the pelvi-ureteric junction and ureter
      using testicular tunica vaginalis autograft].
AB  - AIM: To evaluate the results of surgical reconstruction of the upper urinary
      tract using an autograft of testicular tunica vaginalis in experimental animals.
      MATERIALS AND METHODS: The article presents the results of partial replacement of
      the renal pelvis and ureter with an autograft in 25 male dogs. The grafts were
      harvested by resection of the parietal layer of the testicular tunica vaginalis,
      which was transplanted into the region of the pelvi-ureteric junction and the
      proximal ureter. The upper urinary tract was drained using a ureteral stent
      catheter. The results were evaluated at week 1 and months 1, 3 and six after the
      operation. The functional state of the kidneys and ureters was analyzed using
      excretory urography and ultrasound; the autograft biopsy specimens were examined
      histologically. RESULTS: In all cases, the viability of the autograft was
      completely preserved, there were no signs of secondary infection, necrosis and
      impaired patency in the anastomosis zone. Histological examination revealed signs
      of epithelialization, connective tissue substitution and neovasculogenesis in the
      implantation zone. CONCLUSION: The proposed surgical modality is an alternative
      method to restore normal urine flow in the upper urinary tract in obstructive
      urological diseases. The group of obstructive urological diseases was studied
      using the model of the strictures of the pelvi-ureteric junction in the
      intrarenal pelvis and ureteral strictures measuring up to 3-4 cm in length.

PMID- 29376596
TI  - [Transabdominal and transrectal ultrasound assessment of intravesical prostatic
      protrusion].
AB  - RELEVANCE: Benign prostatic hyperplasia (BPH) is one of the most common
      urological diseases among men. Despite the noticeable positive effects of
      pharmacotherapy on the quality of urination in BPH, the presence of an
      intravesical obstruction (IVO) leads to discontinuation of conservative treatment
      in favor of surgical interventions. One of the features of prostate enlargement
      is the degree of its intravesical growth (intravascular prostatic protrusion,
      IPP). According to some studies, IPP value of 10 mm or more is indicative of IVO
      in virtually all men. AIM: To compare transabdominal and transrectal ultrasound
      measurement of IPP in men with BPH. MATERIALS AND METHODS: The study comprised
      108 men aged 69+/-10 years (43 to 93 years) with lower urinary tract symptoms and
      BPH. Patients underwent a standard urological examination. The shape of the
      prostate, prostate volume and the measurements of the IPP were assessed using
      transabdominal and transrectal ultrasound. RESULTS: The IPP measurements obtained
      using transabdominal and transrectal ultrasound were 9.8+/-5.7 mm (1.1 to 28 mm)
      and 9.3+/-5.3 mm (0.5 to 26 mm), respectively. The IPP measurements evaluated by
      transabdominal and transrectal ultrasound were found comparable regardless of the
      prostate volume. CONCLUSION: Similar results in assessing PPI by both ultrasound
      modalities allow them to be used equally effectively.

PMID- 29376597
TI  - [Experience of 157 vesikoscopic operations in children].
AB  - AIM: Recent advances in the field of minimally invasive surgical technologies in
      children and adolescents have led to the development of vesicoscopic
      (transvesical, pneumoscopic) access (VA). Current limitations in using VA
      emphasize the need for further studies investigating surgical options for the
      management of various pathological conditions of the bladder and ureterovesical
      junction, the features of surgical techniques and the course of the early
      postoperative period when used in pediatric urological practice. MATERIALS AND
      METHODS: From 2013 to 2017, 157 patients (79 girls and 78 boys) aged between 2
      months and 18 years (mean age 4.9-8.7 years) underwent surgery using VD.
      Unilateral and bilateral vesicoscopic ureterocystoneoimplantation was performed
      in 110 (70%) and 44 (28%) patients, respectively. A total of 198 ureters was
      implanted. Three (1.9%) children underwent vesicoscopic excision of the bladder
      diverticulum. Transvesicoscopic Cohen ureteric reimplantation, pneumovesical
      Glenn-Anderson procedure, and Chumakov ureterocystoneoimplantation were performed
      in 151 (96.1%), 2 (1.3%) and 1 (0.6%) patients, respectively. RESULTS: The mean
      operative time when using VA was 126.8+/-46.7 min. In patients younger than one
      year, 1-3 years, 4-17 years, it was 136.0+/-43.8 min, 130.1+/-43.5 min and
      122.4+/-65.8 min, respectively. The mean length of postoperative hospital stay
      was 6.2+/-2.3 days. In 3 (1.9%) cases we had to convert to open surgery. Gas
      migration into the abdominal cavity occurred in 6 (3.8%) patients. Fourteen (9%)
      patients had early postoperative complications. Transient obstruction of
      ureterovesical junction occurred in 6 (3.8%) patients. Acute complete obstruction
      of the distal ureter developed in 3 (1.9%) patients aged three months who did not
      undergo drainage of the upper urinary tract intraoperatively. A paravesical urine
      leak occurred in 1 (0.6%) patient. In one (0.6%) of the boys, the distal end of
      the urinary drainage inserted through the trocar into the ureter migrated in the
      bladder. The urine leakage from the trocar puncture occurred once (0.6%) and was
      stopped by indwelling urethral catheterization for seven days. In 2 (1.3%)
      patients, exacerbation of pyelonephritis required a modification in antibacterial
      therapy. DISCUSSION: Despite the accumulated experience, vesicoscopic surgery
      remains a laborious and complicated surgical intervention, requiring long
      learning curves even for surgeons who have good manual skills in laparoscopic
      surgery. CONCLUSION: In our opinion, vesicoscopic access allows the entire range
      of surgical interventions on the vesicoureteral junction and bladder in children
      to be performed. It is effective, significantly less traumatic than traditional
      open cystotomy access, and associated with an excellent cosmetic result.

PMID- 29376598
TI  - [Analysis of clinical effectiveness and risk factors for complication of
      percutaneous nephrolototripsia in patients with a solitary kidney].
AB  - RELEVANCE: Management of patients with large and staghorn stones of a solitary
      kidney is widely debated among urologists and has not been sufficiently
      investigated, which determined the relevance of this study. MATERIALS AND
      METHODS: The study comprised 80 patients with large (>20 mm) and staghorn stones
      of an anatomically or functionally solitary kidney. Of them, 58 patients
      underwent percutaneous nephrolithotripsy (PNL), and 22 had open surgery. The
      criterion of the treatment effectiveness was the complete stone clearance or
      small residual fragments sized less than 3 mm. The safety criterion was the
      absence of intra- and postoperative complications, according to Clavien-Dindo
      grading system. The study analyzed the following factors influencing the
      effectiveness and safety of PNL: the number of accesses; nephroscope diameter;
      use of a nephroscope sheath; type of lithotripter; size, density, type and
      composition of the stone. RESULTS: Percutaneous nephrolithotripsy demonstrated
      statistically significantly better safety results compared with open surgery with
      comparable effectiveness. Long-term stone recurrence rate after PNL and open
      surgery was 10.4 and 18.2%, respectively. PNL resulted in a statistically
      significant improvement in the kidney function while it worsened after open
      surgery. The effectiveness of PNL depends on the stone type and size and the kind
      of lithotripter. It was 7.5 times greater for a large stone than for staghorn
      calculi and 4.6 times higher for stones sized less or equal 45 mm than for those
      sized > 45 mm. Ultrasonic lithotripter was 2.2 times more effective than another
      type of lithotripter. The safety of PNL depends on the nephroscope diameter, of a
      sheath, the number of accesses, the type of lithotripter and the type of stone.
      Using a 24-Ch nephroscope was 3.6 times safer than that with a diameter greater
      than 24-Ch; not using a sheath was 3.2 times safer than using it; one access was
      3 times safer than at multiple ones; using an ultrasound lithotripter was 2.7
      times safer than with another type of lithotripter; treating a large stone was
      2.1 times safer than a staghorn stone. CONCLUSION: The study findings can be used
      to optimize the treatment of patients with large and staghorn stones of a
      solitary kidney.

PMID- 29376599
TI  - [Effectiveness of laparoscopic repair of primary strictures of ureteropelvic
      junction].
AB  - AIM: To evaluate the effectiveness of laparoscopic repair of primary strictures
      of ureteropelvic junction (UPJ) depending on baseline renal function of the
      ipsilateral kidney. MATERIALS AND METHODS: The study analyzed results of 134
      patients (78 women and 56 men, age from 18 to 56 years) who underwent various
      types of laparoscopic repair of the UPJ stricture from 2012 to 2015. Depending on
      the surgical technique all patients were divided into three groups: group 1
      (n=34) underwent spiral flap technique by Culp and DeWeerd, group 2 (n=59) -
      Anderson-Hynes pyeloplasty and group 3 (n=41) had antevasal dismembered
      pyeloplasty. All interventions ended with internal ureteral stenting for up to 6
      8 weeks. Also, all patients were divided into three subgroups, depending on the
      degree of renal function deficiency - less than 25%, 25-50%, and 51-75%.
      Treatment effectiveness criteria included the following parameters: complete
      relief of the pain syndrome, a decrease in the degree of pyeloectasia,
      stabilization or improvement of the functional state of the renal parenchyma
      (according to radioisotope renography), and the absence of recurrence of the UPJ
      stricture. RESULTS: The overall effectiveness of UPJ laparoscopic reconstruction
      was 94.7% (127 of 134). The effectiveness of the treatment was independent of the
      surgical technique, the initial thickness of the renal parenchyma and the degree
      of PCS dilatation. There was an inverse correlation between the treatment
      effectiveness the degree of kidney function deficiency. CONCLUSION: In patients
      with hydronephrosis secondary to UPJ stricture, the effectiveness of surgical
      treatment is mainly determined by its timeliness. The best treatment results were
      observed in patients with better renal function. The degree of renal function
      deficiency should be considered the main prognostic factor for the effectiveness
      of the forthcoming operation.

PMID- 29376600
TI  - [The role of extraperitoneoscopic adenomectomy in the management of benign
      prostatic hyperplasia greater than 80 cm3].
AB  - INTRODUCTION: The current standard of surgery for benign prostatic hyperplasia
      (BPH) greater than 80 cm3 includes open adenomectomy and holmium enucleation.
      Transurethral resection and laser vaporization are second line interventions,
      while the role of laparoscopic extraperitoneal adenomectomy is not fully
      understood. AIM: To evaluate the role of laparoscopic technique as a surgical
      modality for BPH greater than 80 cm3. MATERIALS AND METHODS: This study
      retrospectively evaluated the results of 79 patients (mean age 68 years) who
      underwent transcapsular extraperitoneoscopic adenomectomy from 2011 to 2016.
      RESULTS: The mean operative time was 206 (100-450) min; the prostate volume was
      134 (80-300) cm3, blood loss was 256 (30-1200) ml. The I-PSS score after surgery
      decreased by an average of 18.3 points, the maximum urinary flow rate increased
      by 12 ml/s, the residual urine volume reduced from 147 to 28 ml. 35 (44%)
      patients underwent simultaneous operations (inguinal hernioplasty,
      cystolithotomy, etc.). There was one intraoperative complication, and 10 (12.6%)
      patients had postoperative complications. There were no conversions to open
      surgery. Incidental prostate cancer was detected in one patient. None of the
      patients required repeat surgery for infravesical obstruction. CONCLUSION:
      Extraperitoneoscopic adenomectomy is efficient, safe and reproducible surgical
      modality able to take the place of open surgery. There is a need for an evidence
      base to support the optimal choice between various minimally invasive techniques.
      Currently, laparoscopic procedure is more justified in patients with concomitant
      diseases, which can be simultaneously corrected.

PMID- 29376602
TI  - [Improving renal cancer care].
AB  - The article reviews the rates of incidence, late diagnosis and mortality from
      kidney cancer in Primorsky Krai. The authors address the issues of improving
      primary and specialized medical care by introducing a three-level health care
      system and restructuring of hospital beds. They propose a new medical technology
      for assessing the individual risk of kidney cancer and present a program of
      measures and organizational modules for prevention, early diagnosis and reduction
      of mortality from kidney cancer.

PMID- 29376601
TI  - [Comparative assessment of treatments for prostate adenoma greater than 100 cm3].
AB  - AIM: To compare holmium laser enucleation of the prostate (HoLEP) and
      endovideosurgical (EVS) adenomectomy in the treatment of prostate adenoma.
      MATERIALS AND METHODS: We compared treatment results of 180 patients with
      prostate adenomas greater than 100 cm3 who underwent EVS adenomectomy (n=90) and
      laser enucleation of the prostate (n=90). The analysis included the following
      parameters: duration of catheterization, length of postoperative hospital stay, I
      PSS score, maximum urinary flow rate measured by uroflowmetry and complications
      according to Clavien-Dindo grading systems. RESULTS: There were no significant
      differences in patient age, preoperative prostate size, glandular tissue weight,
      and operative time. The duration of catheterization (p=0.0008) and length of
      postoperative hospital stay (p<0.0001) were significantly shorter in the HoLEP
      group. Both groups showed a statistically significant improvement in functional
      performance at three months post-surgery. Complications in the HoLEP and EVS
      adenomectomy group occurred in 18 (20%) and 23 (25.55%) patients, respectively
      (p>0.99). CONCLUSION: The two methods mentioned above are widely used in the
      treatment of prostate adenoma. However, holmium laser enucleation of the prostate
      shows similar short-term functional results and complication rates compared with
      EVS adenomectomy for prostate adenomas greater than 100 cm3. The patients of the
      HoLEP group had better results regarding the duration of catheterization and
      length of postoperative hospital stay. Therefore, laser enucleation is the
      preferred surgical modality for prostate adenomas greater than 100 cm3.

PMID- 29376603
TI  - [Results of open and laparoscopic partial nephrectomy for localized renal
      cancer].
AB  - AIM: To compare the results of laparoscopic and open partial nephrectomy.
      MATERIALS AND METHODS: From February 2000 to June 2016, 178 patients (mean age
      58.2 years) with stage T1 kidney tumors underwent partial nephrectomy. This
      cohort included 106 (59.5%) men and 72 (40.5%) women. Open partial nephrectomy
      was performed in 102 (57.3%) patients (group 1) and laparoscopic partial
      nephrectomy (LPL) - 76 (42.7%, 2nd group). The majority (92.2%) of patients
      underwent resection for elective and 14 (7.8%) for absolute indications.
      Preoperatively, 163 (91.6%) and 15 (8.4%) patients had stage T1a stage T1b,
      respectively. The tumor size ranged from 2.4 to 6.2 cm and from 2 cm to 5.4 cm in
      group 1 and 2, respectively. A comparative analysis included operative time, warm
      ischemia time, blood loss, duration of drainage and the length of hospital stay.
      RESULTS: Open partial nephrectomy was associated with shorter operative time (105
      min versus 125 min) and warm ischemia time (14.5 vs. 20.8 min) compared with
      laparoscopic partial nephrectomy. Laparoscopic partial nephrectomy was
      characterized by a smaller blood loss (180 ml vs. 365 ml, p<0.05) and a shorter
      length of hospital stay (2.5 days vs. 5.6 days, p<0.05). One patient from each
      group was found to have positive surgical margins. CONCLUSION: Currently,
      laparoscopic partial nephrectomy is the method of choice for stage T1 kidney
      tumors. Despite the comparatively longer operative time and warm ischemia time,
      laparoscopic partial nephrectomy leads to faster patient recovery and fewer
      complications.

PMID- 29376604
TI  - [Laparoscopic transperitoneal partial nephrectomy for a tumor of the upper
      segment].
AB  - INTRODUCTION: Laparoscopic resection of upper pole kidney tumors is a technically
      challenging procedure. When tumors are located on the dorsal side of the kidney,
      the renal-rotation technique may facilitate laparoscopic partial nephrectomy.
      AIM: To present the technique and results of laparoscopic partial nephrectomy
      (LPN) for tumors of the upper pole of the kidney with its rotation around the
      renal hilum. MATERIAL AND METHODS: The study presents a retrospective analysis of
      the results of 12 patients who underwent LPN for upper pole kidney tumors using
      the renal-rotation technique. The kidney with the renal hilar vessels and the
      upper third of the ureter were mobilized using a transperitoneal access. Then the
      kidney was rotated over its pedicular axis so that the upper pole was located
      inferiorly. As a result, the posterior upper pole tumor was located anteriorly,
      thereby facilitating its resection. After removing the tumor and confirming
      homeostasis, the kidney was returned to its original position. RESULTS: The
      results of LPN using this technique were successful in all 12 patients. The mean
      operative time was 120+/-35.0 (90-210) min, the warm ischemia time was 14.5+/-7.8
      (10-26) min, and the blood loss was 120.0+/-65.5 (60-300) ml. The intraoperative
      complication occurred in 1 (8.3%) patients, postoperative complications were
      observed in 3 patients. Histopathology showed that 11 (91.7%) patients had renal
      cell carcinoma and one (8.3%) had angiomyolipoma. Analysis of early (18.6+/-5.0
      months) oncological outcomes showed no local recurrence and distant metastases.
      CONCLUSION: With dorsally located upper pole kidney tumors, the renal-rotation
      technique facilitates the performance of LPN and minimizes the risk of intra- and
      postoperative complications. This method requires the maximum mobilization of the
      kidney along with the renal hilar vessels and the upper third of the ureter to
      rotate it for optimal resection conditions.

PMID- 29376605
TI  - [Current methods of early diagnosis of prostate cancer].
AB  - Prostate cancer is the most common cancer among men, except for lung cancer.
      Therefore, it is imperative to identify diagnostic methods for early detection of
      prostate cancer to determine patients from healthy populations, which helps guide
      a timely treatment at an initial stage of the disease. The article provides an in
      depth review of the most current diagnostic biomarkers of prostate cancer, their
      role in clinical practice as a means of the early detection and screening for
      prostate cancer.

PMID- 29376606
TI  - [The role of the uretral catheter in the development of catheter- related urinary
      tract infection].
AB  - The most common source of nosocomial infection is the urinary tract, especially
      if they it is drained with a urethral catheter. Catheter-associated urinary tract
      infections account for at least 80% of all complicated urinary tract infections
      and are the most common type of hospital-acquired infection. Intestinal
      microflora plays the leading role in the pathogenesis of catheter-associated
      urinary tract infections, whereas the most important risk factor for their
      development is the long duration of urinary catheter drainage. In the case of
      short-term and intermittent catheterization, routine antibiotic prophylaxis is
      not required, but if a patient develops clinically significant infection,
      antibiotic therapy is required followed by definitive therapy based on culture.
      Urethral catheters coated with antimicrobial substances and anti-inflammatory
      agents can significantly reduce the adhesion and migration of bacteria, thereby
      reducing the incidence of urinary tract infections. Despite this, the incidence
      of catheter-associated infection remains high. We have reviewed recent literature
      related to catheter-associated urinary tract infections and the best means of
      preventing this condition.

PMID- 29376607
TI  - [Idiopathic hypercalciuria. Diagnosis and treatment].
AB  - Most patients with idiopathic hypercalciuria and calcium nephrolithiasis have a
      family history of the disease. Idiopathic hypercalciuria is a metabolic
      abnormality with various causes and developmental pathways. The systematic review
      describes specific mutations associated with idiopathic hypercalciuria and
      nephrolithiasis. Detection of these mutations may provide a better understanding
      of the pathogenesis of this heterogeneous disease and personalize patient
      management depending on the detected polymorphisms. A promising treatment option
      for a mutation in the vitamin D receptor gene is thiazide diuretics in
      combination with bisphosphonates. Among bisphosphonates, the drug of choice which
      has been most strongly supported by research evidence is alendronate.

PMID- 29376608
TI  - [Biomarkers of acute hypoxia-reoxygenation injury to nercycites during
      laparoscopic resection of renal parenchyma].
AB  - Intraoperative occlusion of the renal artery during laparoscopic partial
      nephrectomy results in warm ischemia and nonspecific hypoxia-reoxygenation
      alteration of the renal parenchyma cells with a predominant injury to
      epitheliocytes of the proximal segments of the tubular nephron system. The onset
      and development of acute kidney injury (AKI) syndrome, which requires immediate
      correction, is due to the typical pathological process of cell injury. In this
      regard, the issue of timely diagnosis of AKI remains highly relevant. In patients
      at high risk of developing acute renal failure, detection of AKI biomarkers
      enables early diagnosis. In cases with hypoxia-reoxygenation mediated destruction
      of epithelial cells of tt. renales, related to warm ischemia, the quality of
      diagnosis is significantly improved if the standard work-up is supplemented by
      measurements of the concentration and/or activity of cystatin C, interleukin-18,
      kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty
      acid binding protein, N-acetyl --glucosaminidase, glutathione S-transferase 
      isoform, -glutamyl transpeptidase and lactate dehydrogenase. This article
      provides an overview of published evidence on the properties and diagnostic
      capabilities of biomarkers of warm ischemia related AKI.

PMID- 29376609
TI  - [Concomitant urogenital infections in men].
AB  - The article presents possible combinations of urogenital infections of various
      etiologies and some pathogenetic, clinical and epidemiological features, and
      issues of epidemiological surveillance for co-infection. The authors describe in
      detail combinations with each other and with other diseases of such pathogens as
      Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma spp., Neisseria
      gonorrhoeae, Trichomonas vaginalis. They also focus on the problem of co
      occurrence of human papillomavirus (HPV) with other urogenital pathogens. The
      article raises the question of the need to introduce new scientific data on the
      epidemiology of concomitant urogenital infections in men in the practice of
      diagnosis, treatment, registration, and implementation of preventive and anti
      epidemic measures.

PMID- 29376610
TI  - [The role of stress-induced chronic subclinical inflammation in the pathogenesis
      of the chronic pelvic pain syndrome IIIB in men].
AB  - This literature review of recent clinical and experimental studies describes the
      role of oxidative stress in the multifactorial and interdisciplinary pathogenesis
      of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The
      authors outline general biological nature of oxidative stress and its mechanisms.
      More detailed information is presented on cytokine-mediated chronic subclinical
      inflammation, one of the key mechanisms of oxidative stress, which is currently
      being actively studied. It is shown that the imbalance between pro- and anti
      inflammatory cytokines observed in patients with CPPS-IIIB can explain some
      features of the clinical course (in particular, the characteristics of the pain
      syndrome) and the progression of this disease. In this regard, cytokine profiling
      of prostatic secretion can provide valuable diagnostic, prognostic and monitoring
      information in the management of this category of patients. Recently published
      evidence has demonstrated the essential role of the cytokine-mediated chronic
      inflammatory response as a mechanism of oxidative stress in the pathogenesis of
      CPPS-IIIB. Further studies in this area are warranted and in the long term may
      become a basis for the development of new effective pathogenetic pharmacotherapy
      of CPPS-IIIB.

PMID- 29376611
TI  - [New approaches for recovery of erectile function in patients after radical
      prostatectomy].
AB  - Prostate cancer (PCa) is one of the most common maligmancies and causes of death
      among men. Radical prostatectomy (RP) is optimal and recommended treatment
      modality for localized prostate cancer. More than half of all men undergoing
      surgery experience problems with erectile function and existing treatments do not
      provide a positive effect. Thus, there is a need for new approaches to the
      restoration of erectile function in patients after RP. One of these is the use of
      cell technologies, namely the stromal-vascular fraction and autologous platelet
      rich plasma. This review examines the results of preclinical and clinical studies
      investigating the efficacy and safety of these treatment options in erectile
      dysfunction.

PMID- 29376612
TI  - [The place of mirabegron in clinical practice].
AB  - Currently, a wide range of different drugs is available for te management of
      overactive bladder. This creates problems when it comes to drug selection and
      personalized care for each patient. Mirabegron is the only 3-adrenomimetic agent
      for the treatment of urinary disorders, which, after careful long-term multi
      center randomized trials, has been approved for use in Europe and North America.
      Mirabegron has proven to be very effective in patients who had previously
      received anticholinergic drugs and discontinued them because of the insufficient
      therapeutic effect or pronounced adverse reactions. However, the question of
      using Mirabegron as a first-line treatment for overactive bladder and the
      existing limitations in its administration in clinical urology practice remains
      open.

PMID- 29376613
TI  - [Erectile dysfunction after nerve-sparing radical prostatectomy].
AB  - Nerve-sparing radical prostatectomy remains the optimal curative treatment of
      prostate cancer in patients who want to maintain erectile function. Since its
      development, there has been a gradual decline in its effectiveness concerning the
      prevention of ED, which was associated with the currently more objective
      assessment of erectile function at both the pre- and post-operative stage. There
      is a knowledge gap in the precise understanding of which specific neural
      structures should be preserved with the nerve-sparing technique. At the same
      time, there have been proposed effective methods for visualizing the elements of
      the preserved vascular-neural bundle and estimating the degree of nerve-sparing.

PMID- 29376614
TI  - [A look at the problem of surgical treatment of renal cel carcinoma in the aspect
      of biomolecular diagnosis and assessment of renal function].
AB  - The article reviews the domestic and international literature on the issues of
      biomolecular diagnosis of acute renal injury in the perioperative period in
      patients with renal cell carcinoma (RCC). Emerging opportunities for early
      detection of tumors make even more relevant the use of minimally invasive
      interventions. Of equal importance is the assessment of renal function in
      patients with diagnosed RCC and the prediction of acute renal injury and
      progression of chronic kidney disease in the postoperative period. The authors
      performed a systematic search for preclinical and clinical studies to identify
      the main trends and achievements in the field of biomolecular diagnosis of RCC
      and renal injury allowing the individual approach to choosing surgical treatment,
      improve the survival and quality of life of the patient and improve the
      functional state of the renal parenchyma.

PMID- 29376615
TI  - [Current approaches to conservative treatment of men with concomitant benign
      prostatic hyperplasia and erectile dysfunction].
AB  - The article reviews the results of various conservative treatments for
      concomitant benign prostatic hyperplasia (BPH) and erectile dysfunction (ED).
      Phosphodiesterase type 5 (PDE5) inhibitors remain the first-line therapy for this
      category of patients taking into account their positive effect on both ED and
      BPH. The preferred treatment scheme includes PDE-5 inhibitor co-administered with
      1-adrenoblocker. However, other combination treatments are considered promising,
      for example, a PDE-5 inhibitor with a 5-reductase inhibitor or a three-component
      treatment regimen: 1-adrenoblocker + 5-reductase inhibitor + PDE-5 inhibitor. All
      these approaches to treating patients with BPH and ED have demonstrated high
      efficiency and safety. Nevertheless, a limited number of randomized clinical
      trials and short-term observations suggest the need for further studies
      investigating the long-term outcomes of different treatment options for such
      patients.

PMID- 29376616
TI  - [Laser therapy for mens infertility. Part 2. Systematic review of clinical
      trials].
AB  - Male infertility is a multifactorial syndrome associated with a wide range of
      pathological conditions affecting both the sexual and other body systems:
      endocrine, nervous, blood, and immune. Laser therapy is a form of modern
      physiotherapy that applies low-intensity laser irradiation (LILI) in various
      parts of the body. It is widely used in all areas of modern medicine due to its
      high efficiency, ease of use, the absence of contraindications and side effects.
      The authors reviewed the results of 171 studies investigating laser therapy, of
      which 93 were experimental (20 in Russian and 73 international publications),
      four clinical and experimental (all in Russian), 74 clinical (73 in Russian and 1
      in English).Along with domestic literature, publications in Russian from Belarus,
      Georgia, Kyrgyzstan, Uzbekistan, and Ukraine were also reviewed. The review
      suggests that laser therapy should be used as much as possible in the management
      of male infertility not just due to high effectiveness, but also because of the
      lack of alternatives. For local application, optimal laser irradiation regimens
      are pulsed LILI of red (635 nm) and infrared (904 nm) spectra. For intravenous
      laser blood irradiation, the authors recommend alternating a continuous LILI with
      a wavelength of 635 nm (red spectrum) and 365 nm (ultraviolet spectrum).

PMID- 29376617
TI  - A collaborative approach to developing student placements in care homes.
AB  - If high-quality, person-centred care is to be provided for older people with
      complex needs, it is essential that nurse education should aim to extend
      students' knowledge and skills in longterm care, and integrated health and social
      care. Northumbria University, local care homes and NHS organisations have
      collaborated to develop integrated, cross-sector practice placements that support
      this learning for nursing students. While there have been challenges in
      developing these placements, initial feedback is positive, suggesting the
      placements promote improved interorganisational working and learning for staff as
      well as students.

PMID- 29376618
TI  - A relationship-centred approach to managing pain in dementia.
AB  - The presence of pain in a person with dementia can often be missed. The diagnosis
      of dementia can overshadow the pain-inducing symptoms of other co-morbid
      conditions with distress behaviours being attributed to the behavioural and
      psychological symptoms of dementia. Such distress behaviours of a person with
      dementia often have a profound and alarming effect on family carers. This Admiral
      Nurse case study explores the assessment and management of pain in a person with
      dementia in partnership with the family carer.

PMID- 29376619
TI  - The effect of a leadership support programme on care home managers.
AB  - AIM: To explore the effect of the My Home Life 12-month leadership support
      programme on care home managers' leadership skills and professional development,
      and their relationships with staff, residents and relatives. METHOD: A
      qualitative study of 15 care home managers was undertaken, using focus groups to
      explore the study's aims and objectives. Data were analysed using Colaizzi's
      phenomenological method. FINDINGS: The leadership support programme enabled
      managers to develop their leadership skills, which had a positive effect for them
      and for their relationships with staff, residents and relatives. Conclusion
      Participation in the programme enabled managers to make real practice development
      improvements with meaningful effect for residents.

PMID- 29376620
TI  - Oral misoprostol versus intravaginal dinoprostone for labor induction: a
      comparison study.
AB  - BACKGROUND: Induction of labor (IOL) is one of the most common procedures
      performed in obstetrics, accounting for about the 20% of deliveries in the
      developed countries and it still represents a challenge to obstetricians. The aim
      of this study is the comparison between two techniques for IOL: oral misoprostol
      and Propess(r). METHODS: A retrospective study has been carried out in a single
      tertiary referral center. Clinical maternal, fetal and neonatal information was
      recorded. RESULTS: A total of 863 women were included. the vaginal delivery (VD)
      rate was significantly higher in the misoprostol group. The cesarean section rate
      was comparable between groups. Adverse events and neonatal outcomes were
      comparable between groups. CONCLUSIONS: Misoprostol shows a higher VD rate with
      fewer patients needing a second type of induction and a shorter time to the onset
      of active labor and to VD.

PMID- 29376621
TI  - Transvaginal native-tissue repair of vaginal vault prolapse.
AB  - BACKGROUND: Posthysterectomy vaginal vault prolapse repair is a challenge for
      pelvic floor surgeons. Native-tissue repair procedures imply lower costs and
      reduced morbidity. Our study aims to evaluate operative data, complications,
      objective, subjective and functional outcomes of transvaginal native-tissue
      repair for posthysterectomy vaginal vault prolapse. We also investigated
      differences among available techniques. METHODS: Retrospective study including
      patients with symptomatic vaginal vault prolapse (>=stage 2), previously treated
      with transvaginal vault suspension through native-tissue repair. Objective
      recurrence was defined as the descent of at least one compartment >=II stage
      according to Pelvic Organ Prolapse Quantification (POP-Q) system or need of
      reoperation. Subjective recurrence was defined as the presence of bulging
      symptoms. Patients satisfaction was evaluated with PGI-I Score. RESULTS: The
      study included 111 patients. Apical suspension was achieved either by uterosacral
      ligament suspension (16), levator myorrhaphy (17), iliococcygeus fascia fixation
      (65) or sacrospinous ligament fixation (13). No intraoperative complications were
      observed. Perioperative/postoperative complications occurred in 8 patients
      (7.2%). Mean follow-up was 24.5+/-12.1 months. Objective recurrence was observed
      in 28 patients (25.2%). Reintervention was required by 3 patients (2.7%).
      Subjective recurrence was referred by 6 patients (5.4%). Mean satisfaction
      evaluated with PGI-I Score was 1.2+/-0.6. No differences in terms of operative
      data, overall complications, objective, subjective cure rate and perceived
      satisfaction were found among different techniques. CONCLUSIONS: Transvaginal
      repair with native-tissue procedures is safe and effective in correcting
      posthysterectomy vaginal vault prolapse and represents a valid alternative to
      prosthetic procedures for vaginal vault prolapse treatment.

PMID- 29376622
TI  - [URISCAM project: Multicenter evaluation of the UF-Series cytometer in the
      urinary tract infections screening].
AB  - OBJECTIVE: Urine culture, the gold standard to confirm the presence of urinary
      tract infection (UTI), is the most requested assay in the microbiology
      department. Our objective was to determine the diagnostic yield of the UF-Series
      cytometer as a screening method for UTI. METHODS: All the urine samples sent to
      the six Microbiology Laboratories participating in a period of 5 working days
      were analyzed. We collected demographic variables, apart from those variables
      related to urine samples: source and sample type (midstream, catheterized or
      nephrostomy urines), collection with/without boric acid, cytometer parameters
      (leukocyturia, bacteriuria, bacteria morphology and epithelial cells) and urine
      culture results. ROC curves were plotted to determine predictive capacity of the
      cytometer. RESULTS: A sample of 2,468 patients with average age of 53 years were
      processed (ratio women:men 2:1). Urine culture detected 23% of positive urine
      samples. The predictor variables of UTI were: morphology of bacilli, bacteriuria
      >=21 bacteria/uL, age >=65 years, samples collected in the emergency service and
      hospitalization and preserving conditions. With 21 bacteria/uL as a cut-off
      point, we obtained a sensitivity of 93.3% and 94.5% negative predictive value,
      then reducing the samples to be cultured by 28.9% with 1.6% false negatives.
      CONCLUSIONS: We consider that the UF-Series is a valid and accurate tool for the
      detection of UTI. Therefore, it could be used as screening method in the clinical
      practice prior to the urine culture, reducing culture requirement by
      approximately 30%, with a low false negative rate.

PMID- 29376623
TI  - Interferon-free treatments in patients with hepatitis C genotype 3 infection in a
      tertiary hospital.
AB  - OBJECTIVE: Hepatitis C virus genotype 3 represents a unique entity within HCV
      treatment and multiple studies have documented that HCV genotype 3 infection is
      associated with more rapid disease progression than other genotypes, resulting in
      increased risk of cirrhosis, hepatocellular carcinoma, and all-cause mortality.
      In the current study, we further evaluated the real-world effectiveness of 12
      weeks of ledipasvir/sofosbuvir +/- ribavirin (LDV/SOF +/- RBV) and sofosbuvir +
      daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients
      infected with HCV genotype 3, with or without cirrhosis. METHODS: Retrospective
      and observational study carried out in a third level hospital. Study period:
      April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3
      infection treated either with LDV/SOF +/- RBV or with SOF + DCV during study
      period treated for 12 weeks. The patients that were treated during 24 weeks were
      excluded and those treated with peg-interferon. The main endpoint measured was
      the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary
      endpoint was SVR at 24 weeks (SVR24). RESULTS: During the study period, 603
      patients were treated in our hospital: 71 with genotype 3. We included 46
      patients who were treated with LDV/SOF +/- RBV or SOF + DCV for 12 weeks. A
      43.75% (7/16) of all patients treated with LDV/SOF achieved SVR12, 90% (9/10) of
      the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the
      patients treated with SOF+DCV achieved SVR12. There was statistically significant
      difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with
      regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection.
      CONCLUSIONS: In conclusion, in our cohort of patients, the combination of SOF +
      DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with
      HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those
      without cirrhosis (SVR12 100% in both combinations). All patients who achieved
      SVR12 also achieved SVR24, regardless of the regimen received.

PMID- 29376624
TI  - Investigation of non-saphenous veins in C0S patients.
AB  - BACKGROUND: C0S patients have symptoms of chronic venous disorders (CVDs), though
      an anatomical or pathophysiological explanation is lacking. C0 and C1 classified
      lower limbs can present with valve incompetence from the second to sixth
      generation of tributaries of saphenous veins despite the absence of a detectable
      saphenous truncal reflux. We hypothesized that C0S venous symptoms could stem
      from the second to sixth generation of saphenous tributaries and small veins that
      are not connected to the saphenous system. The aim was to explore these veins in
      C0S subjects and compare them with asymptomatic C0A subjects. METHODS: This was
      an open, controlled study enrolling 36 subjects, where C0S patients (N.=18) were
      compared with asymptomatic C0A subjects (N.=18). The VAS (visual analog scale)
      was used to assess leg pain. Veins were assessed using B-flow ultrasound (valve
      anatomy), continuous-wave (CW) Doppler (flow patterns), biomicroscopy
      (visualization of nutritional vessels), laser Doppler flowmetry (quantify supine
      microvascular perfusion) and quantitative digital photo-plethysmography (PPG)
      (measuring post-exercise venous refilling time [VRT]). RESULTS: There were no
      significant differences between C0S and C0A subjects in terms of microvascular
      perfusion (laser-Doppler), nutritional vessels (biomicroscopy) and VRT (PPG). B
      flow ultrasound was unable to acquire sufficient data in second generation
      saphenous tributaries. However, the CW Doppler identified two different flow
      patterns: uni- and bidirectional. Bidirectional flow was significantly (P=0.05)
      higher in C0S versus C0A patients. CONCLUSIONS: CW Doppler, using a flat high
      sensitivity probe, revealed the presence of a bidirectional flow that was
      significantly (P=0.05) higher in C0S than in control patients, suggesting the
      presence of reflux in non axial veins. These data give a new perspective on the
      management of C0S patients.

PMID- 29376625
TI  - Surgical revision vs. stent-graft to treat venous anastomosis stenosis following
      surgical thrombectomy of hemodialysis grafts.
AB  - BACKGROUND: There is no unanimous strategy for treating stenosis of the venous
      anastomosis (VA) of an occluded arteriovenous graft (AVG) following surgical
      thrombectomy. In this study, we compared classical surgical treatment and
      endovascular treatment procedures with the use of stent- graft in a single center
      study. The aim was to evaluate whether, the VA stenosis of thrombosed AVG treated
      endovascularly by stent-graft implantation, have as good results as surgical VA
      treatment, so that it may be considered the method of choice. METHODS: The study
      included patients who underwent surgical AVG thrombectomy with subsequent
      angiographically confirmed VA stenosis between 1/2009 and 12/2014. Surgical
      angioplasty was then performed in 15 patients and 17 patients underwent primary
      stent-graft implantation. RESULTS: In the surgically treated patients, the
      postintervention primary patency, primary assisted patency and secondary patency
      after 12 months were 50.7%, 56.3%, 62.4%, respectively. In the group of patients
      with occluded AVG who underwent stent-graft implantation, the postintervention
      primary patency, primary assisted patency and secondary patency after 12 months
      were 32.8%, 44.1% a 55.6%, respectively. No statistically significant difference
      in primary patency (P=0.391), primary assisted patency (P=0.605), and secondary
      patency (P=0.702) was observed between the groups. CONCLUSIONS: Stent-graft
      implantation into stenotic VA of an occluded AVG showed to be effective and
      maintained good long-term patency. It is the preferred method due to its minimal
      invasiveness. The superiority of this method must be confirmed on a larger set of
      patients.

PMID- 29376626
TI  - Nanotechnological Strategies for Treatment of Leishmaniasis--A Review.
AB  - The World Health Organization (WHO) estimates that more than one billion people
      suffer from neglected tropical diseases. Leishmaniasis is a widespread disease,
      affecting 12 million people around the world with about 1-2 million estimated new
      cases occurring every year. Although pentavalent antimonial drugs are the most
      frequently prescribed treatments for leishmaniasis, they produce severe side
      effects, including cardiotoxicity and hepatotoxicity. Other compounds, such as
      amphotericin B, pentamidine and miltefosine, are second choice drugs, but they
      also produce side effects that can endanger the patient's life. Nowadays, there
      are two approaches to develop new therapies: one is the search for new drugs and
      the other is the optimization of actual drug formulation. Traditional drug
      discovery takes 10 to 12 years in general and involves high costs; around one
      billion dollars on average to develop a drug. A possibility to improve
      leishmaniasis treatment would be the application of nanotechnology-drug delivery
      systems which can enhance the therapeutic potency of existing drugs by optimizing
      their adsorption, distribution, metabolism and excretion (ADME) and reducing
      toxicity. In this review we will discuss examples how nanotechnology-drug
      delivery systems have been used to improve the therapeutic aspects of existing
      antileishmanial drugs.

PMID- 29376627
TI  - Low Density Lipoprotein Peptide-Conjugated Gold Nanorods for Combating Gastric
      Cancer.
AB  - As a potential drug carrier, the toxicity of gold nanorods (AuNRs) has been
      extensively studied to ensure their safety. Some of these studies reported that
      AuNRs caused a series of toxic cell responses and inspired the hypothesis that
      AuNRs may act as anti-cancer agents. In the present study, we synthesized AuNRs
      (72* 17 nm) and low density lipoprotein (LDL) peptide-RLT modified AuNRs to test
      this hypothesis. A tumor cell inhibition assay was conducted in five cell lines,
      and RLT-AuNRs demonstrated the most efficient inhibition of SGC-7901 cells. RLT
      AuNRs inhibited SGC-7901 cells and increased SGC-7901 cell apoptosis more
      effectively than did AuNRs and DOX in vitro. Treatment with RLT-AuNRs reduced the
      tumor volume, decreased the tumor weight, and enhanced the tumor inhibition
      rates. RLT-AuNRs showed comparable anti-tumor efficacy with DOX but possessed
      higher in vivo safety than did DOX. Nude mice treated with RLT-AuNRs showed good
      health and gained weight during the ten-day anti-tumor therapy. Histological
      results showed no tissue toxicity of RLT-AuNRs. Therefore, RLT-AuNRs may be a
      viable anti-tumor agent for gastric cancer.

PMID- 29376628
TI  - Silica Cross-Linked Micellar Core--Shell Nanoparticles Encapsulating IR-780 with
      Strong Bright and Good Biocompatibility for Optical Imaging In Vivo.
AB  - IR-780 iodide, a near-infrared (NIR) fluorescent heptamethine dye, has attracted
      wide attention in the biomedical community. However, hydrophobicity and toxicity
      severely limit its further biomedical application. Although many successful
      efforts have been made to increase its solubility and biocompatibility, a strong
      fluorescent signal and longer retention time are in high demand in biomedical
      application in vivo as well as basic science research. In this work, we report
      the development of novel silica cross-linked micellar core-shell nanoparticles
      encapsulating IR-780 (NIR-Silica NPs) and their utility for biomedical imaging in
      vivo. Compared to free IR-780, the solubility of NIR-Silica NPs was not only
      greatly increased, but there was also a dramatic 5-7-fold enhancement of
      fluorescence intensity. More importantly, the exceptionally small size (25 nm)
      and colloidal stability of the NPs are also sufficient to realize the enhanced
      permeability and retention effect. In vitro cell viability assays further
      indicated that the NIR-Silica NPs are safer even at the highest concentration
      tested of 1.0 mg/mL. Finally, sentinel lymph node mapping and long-term tumor
      imaging in vivo demonstrated that the NIR-Silica NPs have a long circulation time
      and higher signal-to-noise ratio at a very low dye concentration and short
      exposure time (0.2 s). Therefore, the NIR-Silica NPs may be a promising
      fluorescence imaging agent for clinical application.

PMID- 29376629
TI  - Texture-Dependent Adhesion in Polydopamine Nanomembranes.
AB  - The conformal nature of in situ polymerization of adhesive dopamine molecules
      permits the strong underwater adhesion between polydopamine (PDA) nanomembranes
      and the target substrates. However, the adhesive interaction between the
      postdeposit PDA nanomembranes and other macrobodies is strongly influenced by the
      texture of PDA nanomembranes. Here we report the texture-dependent adhesion of
      PDA nanomembranes both in air and aqueous environments. Despite the nanometer
      scale roughness of PDA nanomembranes, interfacial adhesion between PDA
      nanomembranes and elastomeric bodies are the strong function of the root-mean
      square roughness of PDA nanomembranes, root-mean-square gradient of PDA
      nanomembranes, and the elasticity of the bulk materials. Reduced adhesion due to
      increased texture is intensified in hydrated conditions, possibly hinting that
      the conventional explanation of the negative effect of water to adhesion from a
      molecular level needs to be revisited. These findings can inform the role of
      adhesive interaction in conformal coatings and provide an explanation for the
      differential adhesion observed in freestanding PDA nanomembranes.

PMID- 29376630
TI  - Highly Sensitive and Quality Self-Testable Electrochemiluminescence Assay of DNA
      Methyltransferase Activity Using Multifunctional Sandwich-Assembled Carbon
      Nitride Nanosheets.
AB  - DNA methylation catalyzed by methylase plays a key role in many biological
      activities. However, developing a highly sensitive, simple, and reliable way for
      evaluation of DNA methyltransferase (MTase) activity is still a challenge. Here,
      we report a sandwich-assembled electrochemiluminescence (ECL) biosensor using
      multifunctional carbon nitride nanosheets (CNNS) to evaluate the Dam MTase
      activity. The CNNS could not only be used as an excellent substrate to conjugate
      a large amount of hairpin probe DNA to improve the sensitivity but also be
      utilized as an internal reliability checker and an analyte reporter in the bottom
      and top layers of the biosensor, respectively. Such a unique sandwich
      configuration of CNNS well coupled the advantages of ECL luminophor that were
      generally assembled in the bottom or top layer in a conventional manner. As a
      result, the biosensor exhibited an ultralow detection limit down to 0.043 U/mL
      and a linear range between 0.05 and 80 U/mL, superior to the MTase activity assay
      in most previous reports. We highlighted the great potential of emerging CNNS
      luminophor in developing highly sensitive and smart quality self-testable ECL
      sensing systems using a sandwiched configuration for early disease diagnosis,
      treatment, and management.

PMID- 29376631
TI  - One-Step Preparation of Highly Hydrophobic and Oleophilic Melamine Sponges via
      Metal-Ion-Induced Wettability Transition.
AB  - Hydrophobic and oleophilic absorbent materials have received wide attention in
      recent years for potential applications in pollutant removal from accidental
      spills of oil or organic chemicals. In this work, we report a metal-ion-induced
      hydrophobic melamine sponge (MII-HMS) prepared by a one-step solution immersion
      process. The commercial melamine sponge (intrinsically superhydrophilic with a
      water contact angle of ~0 degrees ) is immersed in an aqueous solution of
      transition metal ions (e.g., FeCl3, Fe(NO3)3, Zn(NO3)2, Ni(NO3)2, and Co(NO3)2)
      for a short period, followed by drying. This simple process renders the
      transition of the superhydrophilic melamine sponge to become highly hydrophobic
      (a water contact angle of ~130 degrees ). Results from X-ray photoelectron
      spectroscopy and infrared spectroscopy suggest that the unprecedented transition
      is likely due to the formation of metal complexes during immersion. The MII-HMS
      is also oleophilic, exhibiting excellent oil absorption capabilities, ~71-157
      times of its weight, for a wide range of oils and organic solvents. Our work
      offers a simple, scalable, and economical approach to fabricate highly efficient
      absorbent materials for potential applications in oil spill recovery and
      environmental remediation.

PMID- 29376632
TI  - Electrochemical Investigation of Natural Ore Molybdenite (MoS2) as a First-Hand
      Anode for Lithium Storages.
AB  - Considering serious pollution from the traditional chemical synthesis process,
      the resource-rich, clean, and first-hand electrode materials are greatly desired.
      Natural ore molybdenite (MoS2), as the low-cost, high-yield, and environmental
      friendly natural source, is investigated as a first-hand anode material for
      lithium-ion batteries (LIBs). Compared with chemosynthetic pure MoS2, natural
      molybdenite provides an ordered ion diffusion channel more effectively owing to
      its excellent characteristics, containing well-crystalline, large lattice
      distance, and trance dopants. Even at a large current density of 2.0 A g-1, a
      natural molybdenite electrode employing a carboxymethyl cellulose binder displays
      an initial charge capacity of 1199 mA h g-1 with a capacity retention of 72%
      after 1000 cycles, much higher than those of the electrodes utilizing a
      poly(vinylidene fluoride) binder. These types of binders play a crucial role in
      stabilizing a microstructure demonstrated by ex situ scanning electron microscopy
      and in affecting pseudocapacitive contributions quantitatively determined by a
      series of kinetic exploration. Briefly, this work might open up a new avenue
      toward the use of natural molybdenite as a first-hand LIB anode in scalable
      applications and deepen our understanding on the fundamental effect of binders in
      the metal-sulfide.

PMID- 29376633
TI  - Organelle-Directed Staudinger Reaction Enabling Fluorescence-on Resolution of
      Mitochondrial Electropotentials via a Self-Immolative Charge Reversal Probe.
AB  - Organelles often feature parameters pertinent to functions and yet responsive to
      biochemical stress. The electropotential across the mitochondrial membrane
      (DeltaPsim) is a crucial mediator of cell fates. Herein we report a bioorthogonal
      reaction enabled fluorescence-on probing of DeltaPsim alterations featuring
      anionic fluorescein-triphenylphosphonium diad (F-TPP), which is released via
      intramitochondria Staudinger reaction triggered self-immolation of o
      azidomethylbenzoylated F-TPP. Compared to classical cationic mitochondria
      specific dyes, F-TPP is hydrophilic and negatively charged. Effectively
      discerning DeltaPsim changes upon diverse stress inducers, the organelle-directed
      bioorthogonal imaging strategy offers unprecedented choices to probe
      mitochondrial biology with functional molecules that are otherwise inaccessible
      via physiological organelle-probe affinity.

PMID- 29376634
TI  - Metal-Organic Framework-Derived Co3ZnC/Co Embedded in Nitrogen-Doped Carbon
      Nanotube-Grafted Carbon Polyhedra as a High-Performance Electrocatalyst for Water
      Splitting.
AB  - The development of efficient, low-cost, and stable electrocatalysts for overall
      water splitting is of great significance for energy conversion. Transition-metal
      carbides (TMCs) with high catalytic activity and low cost have attracted great
      interests. Nevertheless, utilizing an efficient catalyst for overall water
      splitting is still a challenging issue for TMCs. Herein, we report the synthesis
      of a high-performance electrocatalyst comprising Co3ZnC and Co nanoparticles
      embedded in a nitrogen-doped carbon nanotube-grafted carbon polyhedral (Co3ZnC/Co
      NCCP) by the pyrolysis of bimetallic zeolitic imidazolate frameworks in a
      reductive atmosphere of Ar/H2. The Co3ZnC/Co-NCCP exhibits remarkable
      electrochemical activity in catalyzing both the oxygen evolution reaction and
      hydrogen evolution reaction, in terms of low overpotential and excellent
      stability. Furthermore, the Co3ZnC/Co-NCCP catalyst leads to a highly performed
      overall water splitting in the 1 M KOH electrolyte, delivering a current density
      of 10 mA cm-2 at a low applied external potential of 1.65 V and shows good
      stability without obvious deactivation after 10 h operation. The present strategy
      opens a new avenue to the design of efficient electrocatalysts in electrochemical
      applications.

PMID- 29376635
TI  - Single Drop Whole Blood Diagnostics: Portable Biomedical Sensor for Cardiac
      Troponin I Detection.
AB  - Detection of disease biomarkers from whole blood is very important in disease
      prevention and management. However, new generation assays like point-of-care or
      mobile diagnostics face a myriad of challenges in detecting proteins from whole
      blood. In this research, we have designed, fabricated, and characterized a
      portable biomedical sensor for the detection of cardiac troponin I (cTnI)
      directly from whole blood, without sample pretreatments. The sensing methodology
      is based on an extended gate electrical double layer (EDL) gated field effect
      transistor (FET) biosensor that can offer very high sensitivity, a wide dynamic
      range, and high selectivity to target analyte. The sensing methodology is not
      impeded by electrostatic screening and can be applied to all types of FET
      sensors. A portable biomedical system is designed to carry out the diagnostic
      assay in a very simple and rapid manner, that allows the user to screen for
      target protein from a single drop of blood, in 5 min. This biomedical sensor can
      be used in hospitals and homes alike, for early detection of cTnI which is a
      clinical marker for acute myocardial infarction. This sensing methodology could
      potentially revolutionize the modern health care industry.

PMID- 29376636
TI  - In Situ Synthesis and Single Crystal Synchrotron X-ray Diffraction Study of ht
      Sn3Sb2: An Example of How Complex Modulated Structures Are Becoming Generally
      Accessible.
AB  - Recent developments in X-ray sources and detectors and the parallel development
      of software for nonstandard crystallography has made analysis of very complex
      structural problems accessible to nonexperts. Here, we report the successful
      solution of the structure of ht-Sn3Sb2, an analysis that presents several
      challenges but that is still manageable in a relatively straightforward way. This
      compound exists only in a narrow temperature regime and undergoes an unquenchable
      phase transformation on cooling to room temperature; it contains two elements
      with close to identical scattering factors, and the structure is incommensurately
      modulated with four symmetry dependent modulation wave vectors. In this study, an
      attempt was first made to synthesize the title compound by in-house crystal
      growth in the stability region of ht-Sn3Sb2, followed by cooling to room
      temperature. This is known to produce mutiply twinned stistaite and elemental
      tin, and this sample, freshly prepared, was then reheated in situ at the single
      crystal materials beamline Crystal at the synchrotron Soleil. This method was
      unsuccessful as reheating the sample led to loss of Sn from stistaite as revealed
      by a change in the measured modulation wave vector. The compound was instead
      successfully synthesized in situ at the beamline by the topochemical reaction of
      single crystalline stistaite and liquid tin. A well-formed crystal of stistaite
      was enclosed in a quartz capillary together with a large excess of tin and heated
      above the melting point of tin but below the melting point of ht-Sn3Sb2. The
      structure was probed by sychrotron X-ray diffraction using a wavelength close to
      the absorption edge of Sn to maximize elemental contrast. In the diffraction
      patterns, first order satellites were observed, making the structure of ht-Sn3Sb2
      incommensurately modulated. Further analysis exposes four q-vectors running along
      the body diagonals of the cubic unit cell (q1' = alpha alpha alpha, q2' = -alpha
      alpha -alpha, q3' = -alpha -alpha alpha, q4' = alpha -alpha -alpha). To
      facilitate the analysis, the q vectors were instead treated as axial (q1 = alpha
      0 0, q2 = 0 alpha 0, q3 = 0 0 alpha) and an F-type extinction condition for
      satellites was introduced so that only reflections with hklmnp, mnp all odd or
      all even, were considered. Further, the modulation functions F(qi) were set to
      zero, and only modulation functions of the type F(qi') were refined. The final
      model uses the four modulation functions, F(q1'), F(q2'), F(q3'), and F(q4'), to
      model occupancy Sn/Sb and positional modulation. The model shows a structure that
      comprises small NaCl type clusters, typically 7 * 7 * 7 atoms in extension,
      interspersed between single layers of elemental tin. The terminating layers of
      tin are slightly puckered, emulating an incipient deformation toward the
      structure of the layers perpendicular to the [001] direction in elemental tin. It
      is notable that this model is complementary to that of stistaite. In stistaite,
      two-dimensionally infinite slabs of rock salt are interspersed between layers of
      antimony along the trigonal [001] direction, so that the terminating Sb layers
      are the puckered bilayers typical for elemental Sb. Since all modulation
      functions are simple first-order harmonics, the structural model describes a
      locally disordered and most probably dynamic ordering.

PMID- 29376637
TI  - First-Principle Study of Li-Ion Storage of Functionalized Ti2C Monolayer with
      Vacancies.
AB  - Two-dimensional transition metal carbides are notable as promising anode
      materials for Li-ion batteries (LIBs). Using first-principle calculations, we
      investigate the effect of vacancies on the Li adsorption and diffusion on Ti2C
      and Ti2CT2 (where T denotes surface terminations, F or OH) monolayers.
      Interestingly, we find that the carbon vacancies (VC) tend to enhance the
      adsorption of Li in Ti2C monolayer, whereas the titanium vacancies (VTi) play a
      similar role in Ti2CT2 when functional groups present. The presence of vacancies
      further leads to a change in the diffusion behavior of Li atoms. In this context,
      we propose an idea to mitigate the adverse effects on Li diffusion performance by
      regulating the functional groups. In the presence of VC, the surface of Ti2C
      monolayer is suggested to be modified with OH- groups due to its relatively low
      diffusion barrier in the range of 0.025-0.037 eV when Li diffuses around VC,
      whereas in the presence of VTi, the surface is suggested to remove the functional
      groups, resulting in a decrease of energy barrier by about 1 eV when Li atom
      diffuses around VTi. The present study may provide a guideline to improve the Li
      ion storage performance of Ti2C monolayers as electrode materials in LIBs, with
      atomic vacancies being taken into consideration.

PMID- 29376638
TI  - Environmental Impacts by Fragments Released from Nanoenabled Products: A
      Multiassay, Multimaterial Exploration by the SUN Approach.
AB  - Nanoenabled products (NEPs) have numerous outdoor uses in construction,
      transportation or consumer scenarios, and there is evidence that their fragments
      are released in the environment at low rates. We hypothesized that the lower
      surface availability of NEPs fragment reduced their environmental effects with
      respect to pristine nanomaterials. This hypothesis was explored by testing
      fragments generated by intentional micronisation ("the SUN approach"; Nowack et
      al. Meeting the Needs for Released Nanomaterials Required for Further Testing:
      The SUN Approach. Environmental Science & Technology, 2016 (50), 2747). The NEPs
      were composed of four matrices (epoxy, polyolefin, polyoxymethylene, and cement)
      with up to 5% content of three nanomaterials (carbon nanotubes, iron oxide, and
      organic pigment). Regardless of the type of nanomaterial or matrix used, it was
      observed that nanomaterials were only partially exposed at the NEP fragment
      surface, indicating that mostly the intrinsic and extrinsic properties of the
      matrix drove the NEP fragment toxicity. Ecotoxicity in multiple assays was done
      covering relevant media from terrestrial to aquatic, including sewage treatment
      plant (biological activity), soil worms (Enchytraeus crypticus), and fish
      (zebrafish embryo and larvae and trout cell lines). We designed the studies to
      explore the possible modulation of ecotoxicity by nanomaterial additives in
      plastics/polymer/cement, finding none. The results support NEPs grouping by the
      matrix material regarding ecotoxicological effect during the use phase.
      Furthermore, control results on nanomaterial-free polymer fragments representing
      microplastic had no significant adverse effects up to the highest concentration
      tested.

PMID- 29376639
TI  - Unfound Associated Resonant Model and Its Impact on Response of a Quartz Crystal
      Microbalance in the Liquid Phase.
AB  - Quartz crystal microbalance (QCM) is an important tool to detect in real time the
      mass change at the nanogram level. However, for a QCM operated in the liquid
      phase, the Sauerbrey equation is usually disturbed by the changes in liquid
      properties and the longitudinal wave effect. Herein, we report another unfound
      associated high-frequency resonance (HFR) model for the QCM, with the intensity 2
      orders of magnitude higher than that of the fundamental peak in the liquid phase.
      The HFR model exhibits obvious impact on the response of QCM in the thickness
      shear model (TSM), especially for overtones. The frequency of HFR peak is
      decreased dramatically with increasing conductivity or permittivity of the liquid
      phase, resulting in considerable additional frequency shifts in the TSM as
      baseline drift. Compared to that with a faraway HFR peak, the overlapping of HFR
      peak to a TSM overtone results in the frequency shifts of +/-50-70 kHz with its
      intensity enhancement by 3 orders of magnitude in the later. The HFR behavior is
      explained by an equivalent circuit model including leading wire inductance,
      liquid inductance, and static capacitance of QCM. Taking into account the HFR
      model, the positive frequency shifts of the QCM at high overtones during the cell
      adhesion process is understandable. Combining the TSM and HFR is an effective way
      to improve the stability of QCM and provides more reliable information from the
      responses of QCM. The HFR may have potential application in chemical and
      biological sensors.

PMID- 29376640
TI  - Different Response Kinetics to Temperature and Water Vapor of Acrylamide Polymers
      Obtained by Initiated Chemical Vapor Deposition.
AB  - Thermoresponsive polymers undergo a reversible phase transition at their lower
      critical solution temperature (LCST) from a hydrated hydrophilic state at
      temperatures below the LCST to a collapsed hydrophobic state at higher
      temperatures. This results in a strong response to temperature when in aqueous
      environment. This study shows that hydrogel thin films synthesized by initiated
      chemical vapor deposition show fast and strong response to temperature also in
      water vapor environment. Thin films of cross-linked poly(N-isopropylacrylamide),
      p(NIPAAm), were found to have a sharp change in thickness by 200% in water vapor
      at temperatures above and below the LCST. Additionally, the stimuli-responsive
      poly(N,N-diethylacrylamide) was investigated and compared to results found for
      p(NIPAAm). Analysis of the swelling kinetics performed with in situ spectroscopic
      ellipsometry with variable stage temperature shows differences for swelling and
      deswelling processes, and a hysteresis in the thickness profile was found as a
      function of temperature and of temperature change rate.

PMID- 29376641
TI  - Targeted Delivery of a gamma-Glutamyl Transpeptidase Activatable Near-Infrared
      Fluorescent Probe for Selective Cancer Imaging.
AB  - The noninvasive and specific detection of cancer cells in living subjects has
      been essential for the success of cancer diagnoses and treatments. Herein, we
      report a strategy of combining an alphavbeta3-integrin-receptor-targetable
      ligand, c-RGD, with the gamma-glutamyl transpeptidase (GGT)-recognizable
      substrate, gamma-glutamate (gamma-Glu), to develop a tumor-targeting and GGT
      activatable near-infrared (NIR)-fluorescent probe for the noninvasive imaging of
      tumors in living mice. We demonstrated that the probe's fluorescence was off
      initially, but when the gamma-Glu in the probe was specifically cleaved by GGT,
      the fluorescent product was released and could be selectively taken up by U87MG
      tumor cells via alphavbeta3-receptor-mediated endocytosis. Remarkably, enhanced
      intracellular NIR fluorescence distributed mainly in the lysosomes was observed
      in the tumor cells only, showing that the probe was capable of differentiating
      the tumor cells from the GGT-positive, alphavbeta3-deficient normal cells.
      Moreover, the probe also showed a high selectivity for the real-time and
      noninvasive detection of GGT activity in xenograft U87MG tumors following iv
      administration. This study reveals the advantage of using a combination of
      receptor-mediated cell uptake and molecular-target-triggered activation to design
      molecular probes for improved cancer imaging, which could facilitate effective
      cancer diagnoses.

PMID- 29376642
TI  - Bioimaging and Biosensing of Ferrous Ion in Neurons and HepG2 Cells upon
      Oxidative Stress.
AB  - Iron ions, as a main component of intracellular labile iron, not only play an
      important function in oxygen transport, enzymatic reactions, and electron
      transport but also are vitally important in oxidative stress. In this work, we
      developed a ratiometric fluorescent biosensor for ferrous ion (Fe2+), in which
      gold nanoclusters (AuNCs) were synthesized as a stable fluorescent probe and a
      ligand (FeL) was designed for specific recognition of Fe2+ and conjugated onto
      AuNCs (AuNC@FeL). Meanwhile, water-soluble sulfocyanine 7 N-hydroxysuccinimide
      ester (Cy7 NHS ester) was immobilized onto AuNC@FeL as a reference element. The
      developed ratiometric fluorescent nansosensor displayed good linearity with the
      concentration of Fe2+ in the range of 1-105 MUM, and detection limit was achieved
      down to 210 nM. In addition, this nanosensor responded to Fe2+ in less than 1.23
      s and showed high selectivity against other metal ions, amino acids, and reactive
      oxygen species. With the advantages of high selectivity and accuracy, as well as
      quick response and long-term stability, this organic-inorganic ratiometric
      fluorescent probe was successfully applied in real-time biosensing and bioimaging
      of Fe2+ in neurons and HepG2 cells. By use of this tool, it was found that the
      increasing concentration of Fe2+ in live cells was closely related to oxidative
      stress.

PMID- 29376643
TI  - Interface Engineering of High-Performance Perovskite Photodetectors Based on
      PVP/SnO2 Electron Transport Layer.
AB  - Hybrid organic-inorganic perovskites have attracted intensive interest as active
      materials for high-performance photodetectors. However, studies on the electron
      transport layer (ETL) and its influence on the response time of photodetectors
      remain limited. Herein, we compare the performances of perovskite photodetectors
      with TiO2 and SnO2 ETLs, especially on the response time. Both photodetectors
      exhibit a high on/off current ratio of 105, a large detectivity around 1012
      Jones, and a linear dynamic range over 80 dB. The SnO2-based perovskite
      photodiodes show ultrahigh response rates of 3 and 6 MUs for the rise and decay
      times, respectively. However, photodetectors with TiO2 ETLs have low responsivity
      and long response time at low driving voltage, which is attributed to the
      electron extraction barrier at the TiO2/perovskite interface and the charge traps
      in the TiO2 layer. Furthermore, the dark current of SnO2-based perovskite
      photodiodes is effectively suppressed by inserting a poly(vinylpyrrolidone)
      interlayer, and then the on/off current ratio increases to 1.2 * 106,
      corresponding to an improvement of 1 order of magnitude. Such low-cost, solution
      processable perovskite photodetectors with high performance show promising
      potential for future optoelectronic applications.

PMID- 29376644
TI  - NIR Phosphorescent Intramolecularly Bridged Benzoporphyrins and Their Application
      in Oxygen-Compensated Glucose Optode.
AB  - A glucose optode measuring the internal oxygen gradient is presented. The
      multilayer biosensor is composed of (i) analyte-impermeable transparent support,
      (ii) first oxygen-sensing layer combined with an enzymatic layer, (iii) diffusion
      barrier, and (iv) second oxygen-sensing layer. To make this design suitable for
      measurement in subcutaneous tissue, a pair of NIR phosphorescent indicators with
      very different spectral properties is chosen. Combination of a conventional
      Pt(II) tetrabenzoporphyrin dye (absorption and emission maxima at 617 and 772 nm,
      respectively) used in the first layer and a new intramolecularly bridged Pt(II)
      complex (absorption and emission maxima at 673 and 872 nm, respectively) in the
      second layer enables efficient separation of both emission signals. This
      specially designed dye class is accessible via Scholl-reaction from
      tetraphenyltetrabenzoporphyrin complexes. For the first time, the new optode
      allows simultaneous glucose and oxygen measurement in a single spot and therefore
      accurate compensation of oxygen heterogeneities resulting from fluctuations in
      the tissue. The presented material covers the dynamic ranges from 0 to 150 hPa O2
      and from 0 to 360 mg/dL (20 mM) glucose (at 37  degrees C).

PMID- 29376645
TI  - Optimal Laser Wavelength for Femtosecond Ionization of Polycyclic Aromatic
      Hydrocarbons and Their Nitrated Compounds in Mass Spectrometry.
AB  - The ionization and fragmentation processes were examined for a standard sample
      mixture containing 16 polycyclic aromatic hydrocarbons (PAHs) and 3 nitro-PAHs
      (NPAHs) by gas chromatography combined with mass spectrometry (GC/MS) using a
      femtosecond laser emitting at 400, 800, or 1200 nm as the ionization source. The
      signal intensities of NPAHs were lower and the fragmentation more extensive
      compared to those values for PAHs, especially at shorter wavelengths (400 nm).
      These results can be explained by efficient intersystem crossing to triplet
      levels and the shorter excited-state lifetimes of neutral NPAHs molecules,
      compared to the pulse width of the laser. Fragmentation was significantly
      suppressed by nonresonant multiphoton ionization when a laser emitting at longer
      wavelengths (1200 nm) was used. This result can be explained by the absorption
      spectrum of the molecular ion and the excess energy remaining in the ionized
      state. In fact, there was no absorption band at 1200 nm for the molecular ion,
      and the excess energy would be minimal when a near-infrared laser is used, which
      suppresses the fragmentation even for NPAHs. A doubly charged molecular ion was
      observed for PAHs but not for NPAHs, probably owing to the higher stability of
      the PAH molecule, the electrons of which are more strongly bound and are more
      resistive to field ionization. To demonstrate the utility of this technique, the
      sample extracted from particulate matter 2.5 (PM2.5) emitted from a diesel engine
      was measured. NPAHs as well as PAHs were clearly determined at 1200 nm, at which
      the background signal arising from the interference was drastically suppressed.

PMID- 29376646
TI  - Anthropogenic Emissions of Hydrogen Chloride and Fine Particulate Chloride in
      China.
AB  - Particulate chloride (Cl-) can be transformed to nitryl chloride (ClNO2) via
      heterogeneous reaction with nitrogen pentoxide (N2O5) at night. Photolysis of
      ClNO2 and subsequent reactions of chlorine radical with other gases can
      significantly affect the atmospheric photochemistry. In China, the only available
      integrated anthropogenic chloride emission inventory was compiled in the 1990s
      with low spatial resolution, which hinders assessment of impact of ClNO2 on
      current air quality. In this study, we developed an up-to-date and high
      resolution anthropogenic inventory of hydrogen chloride (HCl) and fine
      particulate Cl- emissions in China for 2014 with 0.1 degrees  * 0.1 degrees 
      resolution. Detailed local data and county-level activity data were collected and
      complied. The anthropogenic emissions of HCl and fine particulate Cl- in 2014
      were estimated to be 458 and 486 Gg, respectively. Biomass burning was the
      largest contributor, accounting for 75% of fine particulate Cl- emission and 32%
      of HCl emission. Northeast China and North China Plain were the largest chloride
      emitters. The monthly distribution varied in different regions, due to different
      agricultural activities and climate conditions. This work updates the chloride
      emission information and improves its spatial and temporal resolution, which
      enables better quantification of the ClNO2 production and its impact over China.

PMID- 29376647
TI  - Polyselenide Anchoring Using Transition-Metal Disulfides for Enhanced Lithium
      Selenium Batteries.
AB  - While selenium has recently been proposed as a lithium battery cathode as a
      promising alternative to a lithium-sulfur battery, dissolution of intermediate
      species should be resolved to improve its cycle stability. Here, we report the
      promising results of transition-metal disulfides as an anchoring material and the
      underlying origin for preventing active material loss from the electrode using
      density functional theory calculations. Group 5 and 4 disulfides (VS2, NbS2,
      TaS2, TiS2, ZrS2, and HfS2) in particular show anchoring capabilities superior to
      those of group 6 disulfides (CrS2, MoS2, and WS2). The governing interaction
      controlling the latter relative anchoring strengths is shown to be charge
      transfer as understood by crystal-field theory. The current findings and
      methodologies provide novel chemical insight for the further design of inorganic
      anchoring materials for both lithium-selenium and lithium-sulfur batteries.

PMID- 29376648
TI  - A Mechanistic Understanding of Hydrogen Peroxide Decomposition by Vanadium
      Minerals for Diethyl Phthalate Degradation.
AB  - The interaction of naturally occurring minerals with H2O2 affects the remediation
      efficiency of polluted sites in in situ chemical oxidation (ISCO) treatments.
      However, interactions between vanadium(V) minerals and H2O2 have rarely been
      explored. In this study, H2O2 decomposition by various vanadium-containing
      minerals including V(III), V(IV), and V(V) oxides was examined, and the mechanism
      of hydroxyl radical (*OH) generation for contaminant degradation was studied.
      Vanadium minerals were found to catalyze H2O2 decomposition efficiently to
      produce *OH for diethyl phthalate (DEP) degradation in both aqueous solutions
      with a wide pH range and in soil slurry. Electron paramagnetic resonance (EPR), X
      ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) analyses, and free
      radical quenching studies suggested that *OH was produced via single electron
      transfer from V(III)/V(IV) to H2O2 followed a Fenton-like pathway on the surface
      of V2O3 and VO2 particles, whereas the oxygen vacancy (OV) was mainly responsible
      for *OH formation on the surface of V2O5 particles. This study provides new
      insight into the mechanism of interactions between vanadium minerals and H2O2
      during H2O2-based ISCO.

PMID- 29376649
TI  - Determining Biodegradation Kinetics of Hydrocarbons at Low Concentrations:
      Covering 5 and 9 Orders of Magnitude of Kow and Kaw.
AB  - A partitioning-based experimental platform was developed and applied to determine
      primary biodegradation kinetics of 53 hydrocarbons at ng/L to MUg/L
      concentrations covering C8-C20, 11 structural classes, and several orders of
      magnitude in hydrophobicity and volatility: (1) Passive dosing from a loaded
      silicone donor was used to set the concentration of each hydrocarbon in mixture
      stock solutions; (2) these solutions were combined with environmental water
      samples in gastight auto sampler vials for 1-100 days incubation, and (3)
      automated solid phase microextraction (SPME) coupled to GC-MS was applied
      directly on these test systems for measuring primary biodegradation relative to
      abiotic controls. First order biodegradation kinetics were obtained for 40
      hydrocarbons in activated sludge filtrate, 18 in seawater, and 21 in lake water.
      Water phase half-lives in seawater and lake water were poorly related to
      hydrophobicity and volatility but were, with a few exceptions, within a factor of
      10 or shorter than BioHCwin predictions. The most persistent hydrocarbons,
      1,1,4,4,6-pentamethyldecalin, perhydropyrene, 1,2,3,6,7,8-hexahydropyrene, and
      2,2,4,4,6,8,8-heptamethylnonane, showed limited or inconsistent degradation in
      all three environmental media. This biodegradation approach can cover a large
      chemical space at low substrate concentrations, which makes it highly suited for
      optimizing predictive models for environmental biodegradation.

PMID- 29376650
TI  - Facile Synthesis, Geometry, and 2'-Substituent-Dependent in Vivo Activity of 5'
      (E)- and 5'-(Z)-Vinylphosphonate-Modified siRNA Conjugates.
AB  - (E)-Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5'
      end of the antisense strand, enhances the in vivo potency of siRNA. Here we
      describe a straightforward synthetic approach to incorporate a nucleotide
      carrying a vinylphosphonate (VP) moiety at the 5'-end of oligonucleotides under
      standard solid-phase synthesis and deprotection conditions by utilizing
      pivaloyloxymethyl (POM) protected VP-nucleoside phosphoramidites. The POM
      protection enhances scope and scalability of 5'-VP-modified oligonucleotides and,
      in a broader sense, the synthesis of oligonucleotides modified with phosphonate
      moieties. Trivalent N-acetylgalactosamine-conjugated small interfering RNA
      (GalNAc-siRNA) comprising (E)-geometrical isomer of VP showed improved RISC
      loading with robust RNAi-mediated gene silencing in mice compared to the
      corresponding (Z)-isomer despite similar tissue accumulation. We also obtained
      structural insights into why bulkier 2'-ribosugar substitutions such as 2'-O-[2
      (methylamino)-2-oxoethyl] are well tolerated only when combined with 5'-(E)-VP.

PMID- 29376651
TI  - Increasing Structural Dimensionality of Alkali Metal Fluoridotitanates(IV).
AB  - Reactions between AF (A = Li, Na, K, Rb, Cs) and TiF4 (with starting
      n(AF):n(TiF4) molar ratios in the range from 3:1 to 1:3) in anhydrous hydrogen
      fluoride yield [TiF6]2-, [TiF5]-, [Ti4F19]3-, [Ti2F9]-, and [Ti6F27]3- salts.
      With the exception of the A2TiF6 compounds, which consist of A+ cations and
      octahedral [TiF6]2- anions, all of these materials arise from the condensation of
      TiF6 units. The anionic part in the crystal structures of A[TiF5] (A = K, Cs) and
      A[TiF5].HF (A = Na, K, Rb) is composed of infinite ([TiF5]-)infinity chains built
      of TiF6 octahedra sharing joint vertices. Each structure shows a slightly
      different geometry of the ([TiF5]-)infinity chains. The crystal structure of
      Na[Ti2F9].HF is constructed from polymeric ([Ti2F9]-)infinity anions that appear
      as two parallel infinite zigzag chains comprising TiF6 units, where each TiF6
      unit of one chain is connected to a TiF6 unit of the other chain through a shared
      fluorine vertex. Slow decomposition of single crystals of K4[Ti8F36].8HF and
      Rb4[Ti8F36].6HF ( Shlyapnikov , I. M. ; et al. Chem. Commun. 2013 , 49 , 2703 )
      leads to the formation of [Ti2F9]- (Rb) and [Ti6F27]3- (K, Rb) salts. The former
      displays the same ([Ti2F9]-)infinity double chain as in Na[Ti2F9].HF, while the
      anionic part in the latter, ([Ti6F27]3-)infinity, represents the first example of
      a three-dimensional network built of TiF6 octahedra. The ([Ti6F27]3-)infinity
      anion was also found in [H3O]3[Ti6F27]. The crystal structure determination of
      Cs3[Ti4F19] revealed a new type of polymeric fluoridotitanate(IV) anion,
      ([Ti4F19]3-)infinity. Similar to the ([Ti2F9]-)infinity anion, it is also built
      of zigzag double chains comprising TiF6 units. However, in the former there are
      fewer connections between TiF6 units of two neighboring chains than in the
      latter.

PMID- 29376652
TI  - Retraction of "Mutational Analysis of 48G7 Reveals that Somatic Hypermutation
      Affects Both Antibody Stability and Binding Affinity".

PMID- 29376653
TI  - Redox Chemistry of Bis(pyrrolyl)pyridine Chromium and Molybdenum Complexes: An
      Experimental and Density Functional Theoretical Study.
AB  - The three- and four-membered redox series [Cr(MePDP)2]z (z = 1-, 2-, 3-) and
      [Mo(MePDP)2]z (z = 0, 1-, 2-, 3-) were synthesized to study the redox properties
      of the pincer ligand MePDP2- (H2MePDP = 2,6-bis(5-methyl-3-phenyl-1H-pyrrol-2
      yl)pyridine). The monoanionic complexes were characterized by X-ray
      crystallography, UV/vis/NIR spectroscopy, and magnetic susceptibility
      measurements. Experimental and density functional theory (DFT) studies are
      consistent with closed-shell MePDP2- ligands and +III oxidation states (d3, S =
      3/2) for the central metal ions. Cyclic voltammetry established multiple
      reversible redox processes for [M(MePDP)2]1- (M = Cr, Mo), which were further
      investigated via chemical oxidation and reduction. For molybdenum, one-electron
      oxidation yielded Mo(MePDP)2 which was characterized by X-ray crystallography,
      UV/vis/NIR, and magnetic susceptibility measurements. The experimental and
      computational data indicate metal-centered oxidation to a MoIV complex (d2, S =
      1) with two MePDP2- ligands. In contrast, one- and two-electron reductions were
      found to be ligand centered resulting in the formation of MePDP*3- radicals, in
      which the unpaired electron is predominantly located on the central pyridine ring
      of the ligand. The presence of ligand radicals was established experimentally by
      observation of ligand-to-ligand intervalence charge transfer (LLIVCT) bands in
      the UV/vis/NIR spectra of the dianionic and trianionic complexes and further
      supported by broken-symmetry DFT calculations. X-ray crystallographic analyses of
      the one-electron-reduced species [M(MePDP)2]2- (S = 1, M = Cr, Mo) established
      structural indicators for pincer reduction and showed localization of the radical
      on one of the two pincer ligands. The two-electron-reduced, trianionic complexes
      (S = 1/2) were characterized by UV/vis/NIR spectroscopy, magnetic susceptibility
      measurements, and EPR spectroscopy. The electronic structures of the reduced
      complexes are best described as containing +III metal ions (d3)
      antiferromagnetically coupled to one and two radical ligands for the dianionic
      and trianionic species, respectively.

PMID- 29376654
TI  - Selective Electrocatalytic Reduction of Nitrite to Dinitrogen Based on Decoupled
      Proton-Electron Transfer.
AB  - The development of denitrification catalysts which can reduce nitrate and nitrite
      to dinitrogen is critical for sustaining the nitrogen cycle. However, regulating
      the selectivity has proven to be a challenge, due to the difficulty of
      controlling complex multielectron/proton reactions. Here we report that utilizing
      sequential proton-electron transfer (SPET) pathways is a viable strategy to
      enhance the selectivity of electrochemical reactions. The selectivity of an oxo
      molybdenum sulfide electrocatalyst toward nitrite reduction to dinitrogen
      exhibited a volcano-type pH dependence with a maximum at pH 5. The pH-dependent
      formation of the intermediate species (distorted Mo(V) oxo species) identified
      using operando electron paramagnetic resonance (EPR) and Raman spectroscopy was
      in accord with a mathematical prediction that the pKa of the reaction
      intermediates determines the pH-dependence of the SPET-derived product. By
      utilizing this acute pH dependence, we achieved a Faradaic efficiency of 13.5%
      for nitrite reduction to dinitrogen, which is the highest value reported to date
      under neutral conditions.

PMID- 29376655
TI  - Penning Ionization of Acene Molecules by Helium Nanodroplets.
AB  - Acene molecules (anthracene, tetracene, pentacene) and fullerene (C60) are
      embedded in He nanodroplets (HeN) and probed by EUV synchrotron radiation. When
      resonantly exciting the He nanodroplets, the embedded molecules M are efficiently
      ionized by the Penning reaction HeN* + M -> HeN + M+ + e-. However, the Penning
      electron spectra are all broad and structureless, largely differing from those
      measured by binary Penning collisions, as well as from those measured for dopants
      bound to the He droplet surface. Simulations based on elastic binary electron-He
      collisions qualitatively reproduce the measured spectra only when assuming
      unexpectedly large He droplets, indicating that electron spectra of molecules
      embedded in helium nanodroplets are severely affected by collective electron
      helium interactions.

PMID- 29376656
TI  - Conformations of Protonated AlaDap and DapAla Characterized by IRMPD Spectroscopy
      and Molecular Modeling.
AB  - Oligopeptides containing 2,3-diaminopropionic acid (Dap) serve as a unique model
      to study conformational effects on the ionizability of a side-chain group. In
      this study, conformations of acetylated isomeric dipeptide ions containing
      alanine (Ala) and Dap, AlaDapH+ and DapAlaH+, are studied by infrared multiple
      photon dissociation (IRMPD) spectroscopy and computation. The IRMPD spectra are
      characterized in detail by comparing them with theoretical IR spectra of a set of
      low-energy conformations calculated at the omegaB97X-D/6-311+G(d) level of
      theory. The averaged IR spectra according to the Boltzmann distribution of the
      set of conformations have a good match to the IRMPD spectra. The characteristic
      amide I band of AlaDapH+ appears to be downshifted compared to that of DapAlaH+.
      The relative positions of the amide band suggest a stronger hydrogen-bonding
      interaction between the charged side-chain amino group and the amide carbonyl
      groups in AlaDapH+ than in DapAlaH+. The stronger hydrogen bonding in the former
      is likely due to a better alignment of the N-H and O?C bonds, which enables an
      effective sequestering of the positive charge at the amino group. The effect
      results in a higher proton affinity of acetylated dipeptides with the Dap residue
      at the C-terminus.

PMID- 29376657
TI  - Acaulide, an Osteogenic Macrodiolide from Acaulium sp. H-JQSF, an Isopod
      Associated Fungus.
AB  - Acaulide (1), a macrodiolide with an unprecedented framework, was characterized
      along with its shunt products-acaulones A (2) and B (3)-from the culture of
      Acaulium sp. H-JQSF associated with the isopod Armadillidium vulgare. The spiro
      linked 14-, 14-, and 6-membered cycles of 1 arise likely from iterative
      intermolecular Michael addition reactions. Biological evaluation in the
      prednisolone-induced osteoporotic zebrafish demonstrated that 1 is
      antiosteoporotic at 0.4 and 2.0 MUM.

PMID- 29376658
TI  - Tandem Rh-Catalyzed [4 + 2] Vinylic C-H O-Annulation of Exocyclic Enones with
      Alkynes and 1,5-H Shift.
AB  - Active pyrylium intermediates are in situ generated by a Rh-catalyzed vinylic C-H
      annulation reaction between exocyclic alpha,beta-enones and alkynes, which
      undergo a base-promoted rearrangement via 1,5-H shift to form 1H-benzo[f]chromene
      derivatives.

PMID- 29376660
TI  - Perceived Child Weight Status, Family Structure and Functioning, and Support for
      Health Behaviors in a Sample of Bariatric Surgery Patients.
AB  - INTRODUCTION: The purpose of this study is to describe the associations between
      bariatric surgery patients' perspectives of their child's weight status, family
      support for eating and exercise behavior change, and family structure and
      functioning. METHOD: A cross-sectional descriptive design with pre- and
      postsurgery (N = 224) patients was used. Demographics, perceptions of child
      weight status, family support for eating habits and exercise, and family
      functioning were assessed from patients at a University Bariatric Clinic.
      RESULTS: Patients who perceived their child to be overweight/obese reported more
      impaired family functioning, less family exercise participation, and more
      discouragement for eating habit change in the family compared to patients who did
      not perceive their child to be overweight/obese. Single parents more often
      perceived their children to be overweight/obese, and had more impaired family
      functioning, and less support for changing eating habits and family exercise
      participation. Patients with impaired family functioning reported less support
      for changing eating habits and family exercise participation. DISCUSSION:
      Bariatric patients who perceived their child to be overweight/obese and
      identified as single parents reported more impaired family functioning and less
      support for eating habits and family participation in exercise. Assessing pre-
      and postsurgery measures from parents and children will allow the further
      identification of relationship variables that can be targeted to promote positive
      family changes that benefit parents and children long-term. (PsycINFO Database
      Record

PMID- 29376659
TI  - Parsimonious Charge Deconvolution for Native Mass Spectrometry.
AB  - Charge deconvolution infers the mass from mass over charge (m/z) measurements in
      electrospray ionization mass spectra. When applied over a wide input m/z or broad
      target mass range, charge-deconvolution algorithms can produce artifacts, such as
      false masses at one-half or one-third of the correct mass. Indeed, a maximum
      entropy term in the objective function of MaxEnt, the most commonly used charge
      deconvolution algorithm, favors a deconvolved spectrum with many peaks over one
      with fewer peaks. Here we describe a new "parsimonious" charge deconvolution
      algorithm that produces fewer artifacts. The algorithm is especially well-suited
      to high-resolution native mass spectrometry of intact glycoproteins and protein
      complexes. Deconvolution of native mass spectra poses special challenges due to
      salt and small molecule adducts, multimers, wide mass ranges, and fewer and lower
      charge states. We demonstrate the performance of the new deconvolution algorithm
      on a range of samples. On the heavily glycosylated plasma properdin glycoprotein,
      the new algorithm could deconvolve monomer and dimer simultaneously and, when
      focused on the m/z range of the monomer, gave accurate and interpretable masses
      for glycoforms that had previously been analyzed manually using m/z peaks rather
      than deconvolved masses. On therapeutic antibodies, the new algorithm facilitated
      the analysis of extensions, truncations, and Fab glycosylation. The algorithm
      facilitates the use of native mass spectrometry for the qualitative and
      quantitative analysis of protein and protein assemblies.

PMID- 29376661
TI  - Characterizing cognitive and visuomotor control in children with sensory
      processing dysfunction and autism spectrum disorders.
AB  - OBJECTIVE: Children with autism spectrum disorders (ASD) and sensory processing
      dysfunction (SPD) are reported to show difficulties involving cognitive and
      visuomotor control. We sought to determine whether performance on computerized,
      behavioral measures of cognitive control aimed at assessing selective attention,
      as well as visuomotor abilities differentiated children with ASD (n = 14), SPD (n
      = 14) and typically developing controls (TDC; n = 28). METHOD: Cognitive control
      differences were measured by assessing selective attention-based abilities both
      with and without distracting stimuli, and visuomotor differences were measured by
      characterizing visuomotor tracking and tracing skills. Performance in cognitive
      control and visuomotor domains were investigated globally as composite scores,
      and specifically within each task. RESULTS: Our results indicated that though the
      ASD group showed the most impaired selective attention performance, the SPD group
      had intermediate abilities-performing above the ASD group but below the TDC
      group. Furthermore, both the SPD and ASD groups demonstrated equally impaired
      visuomotor abilities relative to the TDC group. A correlational analysis between
      cognitive and visuomotor control suggest a relationship between these overlapping
      control networks. CONCLUSIONS: This study supports the importance of direct,
      phenotypic characterizations of control-based abilities in children with ASD and
      SPD to personalize characterization and treatment interventions for at-risk
      children. (PsycINFO Database Record

PMID- 29376662
TI  - The painful duality of envy: Evidence for an integrative theory and a meta
      analysis on the relation of envy and schadenfreude.
AB  - Despite envy's importance as a driver of social behavior, scholars disagree on
      its conceptualization. We review the literature and distinguish three incongruent
      theories: (a) Malicious Envy Theory (i.e., envy as uniform and malicious), (b)
      Dual Envy Theory (i.e., envy as taking on 2 forms, benign and malicious), and (c)
      Pain Theory of Envy (i.e., envy as uniform and driven by pain). Moreover, within
      and across theories, operationalizations of envy have included various different
      components. We integrate these conceptualizations using a data-driven approach,
      deriving a comprehensive theory of envy in 5 studies (total N = 1,237)-the Pain
      driven Dual Envy (PaDE) Theory. Exploratory and confirmatory factor analyses of
      an exhaustive set of envy components (Studies 1-4) suggest that envy consists of
      3 factors: Pain (i.e., preoccupation with the envy-eliciting situation,
      inferiority), predicts both benign envy (i.e., desire for the envy object,
      improvement motivation, emulation of the other), and malicious envy (i.e.,
      communication about the other, directed aggression, nondirected aggression). An
      experience-sampling study (Study 5) suggests that pain constitutes a quickly
      fading reaction, whereas benign and malicious envy are enduring attitudinal
      constructs. We apply this theory in a meta-analysis on the controversial relation
      of envy and schadenfreude (N = 4,366), finding that envy and schadenfreude are
      more strongly and positively correlated to the extent that the respective
      research operationalizes envy as malicious, compared with as pain or benign envy.
      We discuss how the PaDE Theory can illuminate research on envy in diverse
      settings, and envy's relation to other distinct emotions. (PsycINFO Database
      Record

PMID- 29376663
TI  - Motivation moderates the effects of social support visibility.
AB  - Social support can sometimes have negative consequences for recipients. One way
      of circumventing these negative effects is to provide support in an 'invisible'
      or indirect manner, such that recipients do not construe the behavior as a
      supportive act. However, little is known about how recipients' motivational
      states influence when visible (direct) support or invisible support is more
      beneficial. Using the framework of Regulatory Mode Theory, we predicted that
      recipients motivated to engage in critical evaluation (i.e., those with a
      predominant assessment motivation) would find invisible support more beneficial
      than visible support, whereas recipients motivated to initiate action (i.e.,
      those with a predominant locomotion motivation) would find visible support more
      beneficial than invisible support. Findings from one 2 * 2 experiment (Study 1),
      two laboratory experiments (Studies 2-3), one dyadic study involving support
      conversations between friends (Study 4), and a meta-analysis aggregating data
      from all four studies supported these hypotheses. As predicted, support outcomes
      were better for assessment predominant recipients following invisible support,
      but were better for locomotion predominant recipients following visible support.
      Results indicate that support attempts could be made more effective by
      considering both support visibility and recipient motivation. (PsycINFO Database
      Record

PMID- 29376664
TI  - Personality Trait Development Across the Transition to Retirement.
AB  - In this study, we examined trajectories of Big Five personality development in
      the 5 years before and after retirement. Our sample was composed of 690 retirees
      (ages 51-81) and a propensity-score matched comparison group of 532 nonretirees
      drawn from a nationally representative longitudinal study of the Netherlands.
      Participants contributed data across a maximum of 6 measurement waves over a
      period of 7 years. In the month after retirement, participants experienced sudden
      increases in openness and agreeableness followed by gradual declines in these
      traits over the next 5 years. Emotional stability increased before and after
      retirement. The transition to retirement was not associated with changes in
      conscientiousness or extraversion. Further, we found significant individual
      differences in development across the transition to retirement for each
      personality trait but could not identify any moderators that accounted for these
      individual differences. These results contribute to our understanding of
      personality development in older adulthood as well as the temporal dynamics of
      personality change in response to major life events. (PsycINFO Database Record

PMID- 29376665
TI  - Utilization of primary care among college students with mental health disorders.
AB  - OBJECTIVE: Our goal was to assess whether integration of behavioral and medical
      services in college settings is associated with decreased use of primary care by
      patients with mental health diagnoses (MHDs). METHOD: The cohort consisted of
      80,219 patients with at least 1 MHD in 21 universities. Two levels of service
      integration were defined: "standard"-universities with separate electronic health
      records (EHR) systems and minimal clinical collaboration between services, and
      "enhanced"-universities with shared EHR and collaborative patient care.
      Frequency, the total number of primary care visits, and complexity, the total
      visit length for primary care per unit time, were compared by using multilevel
      models. RESULTS: Nine schools met the criteria of enhanced clinical integration;
      a tenth school shifted to enhanced service during the study period. Student and
      patient demographics and clinical diagnoses were similar between the 2
      categories. When controlling for variance in age, sex, and total time in school,
      patients with MHDs in standard systems had 15.72% (95% confidence interval [CI]:
      10.77%-20.44%) more primary care visits and 22.88% (95% CI: 21.42%-24.38%) more
      time than patients in enhanced systems. CONCLUSIONS: Students with MHDs have
      significantly lower utilization of primary care services in integrated health
      care systems, but only a minority of institutions nationally have adopted this
      model of care. Although further research is needed to specifically assess
      differences in health outcomes and perceived suffering, it is possible that
      reduced primary care visits in enhanced integrative service settings with robust
      mental health support indicates overall reduction in perceived suffering for
      patients/clients. (PsycINFO Database Record

PMID- 29376666
TI  - Celebrating the 125th anniversary of the American Psychological Association: A
      quarter century of neuropsychology.
AB  - OBJECTIVE: The American Psychological Association (APA) celebrated its 125th
      anniversary in 2017. As part of this celebration, the APA journal Neuropsychology
      has published in its November 2017 issue 11 papers describing some of the
      advances in the field of neuropsychology over the past 25 years. METHOD: The
      papers address three broad topics: assessment and intervention, brain imaging,
      and theory and methods. RESULTS: The papers describe the rise of new assessment
      and intervention technologies, the impact of evidence for neuroplasticity on
      neurorehabilitation. Examples of the use of mathematical models of cognition to
      investigate latent neurobehavioral processes, the development of the field of
      neuropsychology in select international countries, the increasing sophistication
      of brain imaging methods, the recent evidence for localizationist and
      connectionist accounts of neurobehavioral functioning, the advances in
      neurobehavioral genomics, and descriptions of newly developed statistical models
      of longitudinal change. CONCLUSION: Together the papers convey evidence of the
      vibrant growth in the field of neuropsychology over the quarter century since
      APA's 100th anniversary in 1992. (PsycINFO Database Record

PMID- 29376669
TI  - Is clinical virtual reality ready for primetime?
AB  - OBJECTIVE: Since the mid-1990s, a significant scientific literature has evolved
      regarding the outcomes from the use of what we now refer to as clinical virtual
      reality (VR). This use of VR simulation technology has produced encouraging
      results when applied to address cognitive, psychological, motor, and functional
      impairments across a wide range of clinical health conditions. This article
      addresses the question, "Is clinical VR ready for primetime?" METHOD: After a
      brief description of the various forms of VR technology, we discuss the
      trajectory of clinical VR over the last 20 years and summarize the basic assets
      that VR offers for creating clinical applications. The discussion then addresses
      the question of readiness in terms of the theoretical basis for clinical VR
      assets, the research to date, the pragmatic factors regarding availability,
      usability, and costs of clinical VR content/systems, and the ethical issues for
      the safe use of VR with clinical populations. RESULTS: Our review of the
      theoretical underpinnings and research findings to date leads to the prediction
      that clinical VR will have a significant impact on future research and practice.
      Pragmatic issues that can influence adoption across many areas of psychology also
      appear favorable, but professional guidelines will be needed to promote its safe
      and ethical use. CONCLUSIONS: Although there is still much research needed to
      advance the science in this area, we strongly believe that clinical VR
      applications will become indispensable tools in the toolbox of psychological
      researchers and practitioners and will only grow in relevance and popularity in
      the future. (PsycINFO Database Record

PMID- 29376667
TI  - How technology is reshaping cognitive assessment: Lessons from the Framingham
      Heart Study.
AB  - OBJECTIVE: This article elucidates how the Boston process approach (BPA) can
      amplify the role of neuropsychology in the study of preclinical and clinical
      dementia, particularly Alzheimer's disease (AD), and how advancements in
      technology expand BPA capacity objectively and exponentially. METHOD: The BPA is
      based on a conceptualization of cognition as being comprised of multiple
      processes, the nature of which could not possibly be captured by a single score
      on a test or battery of tests. Identification of these processes is only possible
      with careful observation of an individual during the entire testing process to
      determine how, when, and why a person fails, which helps to reveal the integrity
      of the cognitive processes underlying the behavior. RESULTS: BPA use within the
      Framingham Heart Study is described, including how digital technology has been
      incorporated to enhance the sensitivity of BPA to detect insidious onset changes
      even earlier than had been previously possible. The digital technology movement
      will dramatically alter the means by which cognitive function is assessed going
      forward. CONCLUSIONS: Technological advances will catalyze groundbreaking
      discoveries for effective treatments of neurodegenerative cognitive disorders,
      such as AD, and inform novel strategies for dementia prevention and sustained
      lifelong cognitive health. (PsycINFO Database Record

PMID- 29376668
TI  - Quantitative modeling of category learning deficits in various patient
      populations.
AB  - OBJECTIVE: To provide a select review of our applications of quantitative
      modeling to highlight the utility of such approaches to better understand the
      neuropsychological deficits associated with various neurologic and psychiatric
      diseases. METHOD: We review our work examining category learning in various
      patient populations, including individuals with basal ganglia disorders
      (Huntington's Disease and Parkinson's disease), amnesia and Eating Disorders.
      RESULTS: Our review suggests that the use of quantitative models has enabled a
      better understanding of the learning deficits often observed in these conditions
      and has allowed us to form novel hypotheses about the neurobiological bases of
      their deficits. CONCLUSIONS: We feel that the use of neurobiologically inspired
      quantitative modeling holds great promise in neuropsychological assessment and
      that future clinical measures should incorporate the use of such models as part
      of their standard scoring. Appropriate studies need to be completed, however, to
      determine whether such modeling techniques adhere to the rigorous psychometric
      properties necessary for a valid and reliable application in a clinical setting.
      (PsycINFO Database Record

PMID- 29376670
TI  - International growth of neuropsychology.
AB  - OBJECTIVE: Twenty-five years ago, the field of neuropsychology was well
      established in North America, Europe, and Australia, with less presence
      elsewhere. This article discusses the development of neuropsychology over the
      last 25 years in other regions. METHOD: The growth of neuropsychology in Asia,
      Africa, the Middle East, Central and South America, and New Zealand is reviewed.
      Sources drawn on include a 2016 edition of The Clinical Neuropsychologist
      describing the practice of neuropsychology in 18 countries; papers on the
      profession of neuropsychology in Latin America (Arango-Lasprilla, Stevens,
      Paredes, Ardila, & Rivera, 2016), the history of neuropsychology in Asia (Lee,
      Wang, & Collinson, 2016), and neuropsychology in Central America (Judd, 2017);
      INSNET; and personal communications. CONCLUSIONS: There has been tremendous
      variability in the development of neuropsychology across these regions over the
      last 25 years. Obstacles to the growth of neuropsychology have included economic
      constraints on health care provision, limited availability of appropriate
      assessment and treatment methods, linguistic diversity and illiteracy, stigma
      toward and/or lack of awareness of neuropsychological disorders, lack of graduate
      training and clinical supervision, absence of accreditation of neuropsychologists
      as a clinical profession, poor pay, and diminished visibility of the field within
      the regional culture. Despite these obstacles, neuropsychological research and
      practice is establishing itself in these regions and has grown significantly over
      the last quarter century. Major challenges remain in establishing awareness of
      the significance of and developing culturally appropriate methods of assessing
      and rehabilitating cognitive aspects of brain disorders, training programs,
      recognition as a profession, and dedicated funding for neuropsychology positions.
      (PsycINFO Database Record

PMID- 29376671
TI  - Structural neuroimaging in neuropsychology: History and contemporary
      applications.
AB  - OBJECTIVE: Neuropsychology's origins began long before there were any in vivo
      methods to image the brain. That changed with the advent of computed tomography
      in the 1970s and magnetic resonance imaging in the early 1980s. Now computed
      tomography and magnetic resonance imaging are routinely a part of
      neuropsychological investigations with an increasing number of sophisticated
      methods for image analysis. METHOD: This review examines the history of
      neuroimaging utilization in neuropsychological investigations, highlighting the
      basic methods that go into image quantification and the various metrics that can
      be derived. Neuroimaging methods and limitations for identify what constitutes a
      lesion are discussed. Likewise, the influence of various demographic and
      developmental factors that influence quantification of brain structure are
      reviewed. CONCLUSIONS: Neuroimaging is an integral part of 21st Century
      neuropsychology. The importance of neuroimaging to advancing neuropsychology is
      emphasized. (PsycINFO Database Record

PMID- 29376673
TI  - Neuropsychology's social landscape: Common ground with social neuroscience.
AB  - Looking back 25 years into neuropsychology's past coincides almost perfectly with
      the birth of social neuroscience as a discipline. Social neuroscience aims to
      identify the biological bases of social behavior through multilevel analyses of
      neural, cognitive, and social processes. Neuropsychology, on the other hand,
      aspires to understand brain-behavior relationships more generally. Given that
      much of human behavior comprises social interactions, the goals, theories,
      methods, and findings derived from social neuroscience are likely to have bearing
      on the issues and interests of neuropsychologists. This review summarizes some of
      the main developments that have emerged from social neuroscience and their
      relevance to neuropsychology. Applications of social neuroscience principles are
      presented in the context of brain insult, assessment, and intervention.
      Recommendations are made for improving neuropsychological approaches to the
      evaluation of social cognition and competence. In closing, a discussion of the
      challenges and possible future directions for the 2 disciplines is offered.
      (PsycINFO Database Record

PMID- 29376672
TI  - Functional brain imaging in neuropsychology over the past 25 years.
AB  - OBJECTIVE: Outline effects of functional neuroimaging on neuropsychology over the
      past 25 years. METHOD: Functional neuroimaging methods and studies will be
      described that provide a historical context, offer examples of the utility of
      neuroimaging in specific domains, and discuss the limitations and future
      directions of neuroimaging in neuropsychology. RESULTS: Tracking the history of
      publications on functional neuroimaging related to neuropsychology indicates
      early involvement of neuropsychologists in the development of these
      methodologies. Initial progress in neuropsychological application of functional
      neuroimaging has been hampered by costs and the exposure to ionizing radiation.
      With rapid evolution of functional methods-in particular functional MRI (fMRI)
      neuroimaging has profoundly transformed our knowledge of the brain. Its current
      applications span the spectrum of normative development to clinical applications.
      The field is moving toward applying sophisticated statistical approaches that
      will help elucidate distinct neural activation networks associated with specific
      behavioral domains. The impact of functional neuroimaging on clinical
      neuropsychology is more circumscribed, but the prospects remain enticing.
      CONCLUSIONS: The theoretical insights and empirical findings of functional
      neuroimaging have been led by many neuropsychologists and have transformed the
      field of behavioral neuroscience. Thus far they have had limited effects on the
      clinical practices of neuropsychologists. Perhaps it is time to add training in
      functional neuroimaging to the clinical neuropsychologist's toolkit and from
      there to the clinic or bedside. (PsycINFO Database Record

PMID- 29376674
TI  - Cognitive genomics: Searching for the genetic roots of neuropsychological
      functioning.
AB  - OBJECTIVE: Human cognition has long been known to be under substantial genetic
      control. With the complete mapping of the human genome, genome-wide association
      studies for many complex traits have proliferated; however, the highly polygenic
      nature of intelligence has made the identification of the precise genes that
      influence both global and specific cognitive abilities more difficult than
      anticipated. METHOD: Here, we review the latest developments in the genomics of
      cognition, including a discussion of methodological advances in the genetic
      analysis of complex traits, and shared genetic contributions to cognitive
      abilities and neuropsychiatric disorders. RESULTS: A wealth of twin and family
      studies have provided compelling evidence for a strong heritable component of
      both global and specific cognitive abilities, and for the existence of
      "generalist genes" responsible for a large portion of the variance in diverse
      cognitive abilities. Increasingly sophisticated analytic tools and ever-larger
      sample sizes are now facilitating the identification of specific genetic and
      molecular underpinnings of cognitive abilities, leading to optimism regarding
      possibilities for novel treatments for illnesses related to cognitive function.
      CONCLUSIONS: We conclude with a set of future directions for the field, which
      will further accelerate discoveries regarding the biological pathways relevant to
      cognitive abilities. These, in turn, may be further interrogated in order to link
      biological mechanisms to behavior. (PsycINFO Database Record

PMID- 29376677
TI  - Quantum-Limited Directional Amplifiers with Optomechanics.
AB  - Directional amplifiers are an important resource in quantum-information
      processing, as they protect sensitive quantum systems from excess noise. Here, we
      propose an implementation of phase-preserving and phase-sensitive directional
      amplifiers for microwave signals in an electromechanical setup comprising two
      microwave cavities and two mechanical resonators. We show that both can reach
      their respective quantum limits on added noise. In the reverse direction, they
      emit thermal noise stemming from the mechanical resonators; we discuss how this
      noise can be suppressed, a crucial aspect for technological applications. The
      isolation bandwidth in both is of the order of the mechanical linewidth divided
      by the amplitude gain. We derive the bandwidth and gain-bandwidth product for
      both and find that the phase-sensitive amplifier has an unlimited gain-bandwidth
      product. Our study represents an important step toward flexible, on-chip
      integrated nonreciprocal amplifiers of microwave signals.

PMID- 29376678
TI  - Electrostatically Tunable Adhesion in a High Speed Sliding Interface.
AB  - Contact hysteresis between sliding interfaces is a widely observed phenomenon
      from macro- to nanoscale sliding interfaces. Most such studies are done using an
      atomic force microscope (AFM) where the sliding speed is a few MUm/s. Here, we
      present a unique study on stiction between the head-disk interface of
      commercially available hard disk drives, wherein the vertical clearance between
      the head and the disk is of the same order as in various AFM-based fundamental
      studies but with a sliding speed that is nearly 6 orders of magnitude higher. We
      demonstrate that, although the electrostatic force (dc or ac voltage) is an
      attractive force, the ac-voltage-induced out-of-plane oscillation of the head
      with respect to the disk is able to completely suppress the contact hysteresis.

PMID- 29376679
TI  - Quantum Transduction with Adaptive Control.
AB  - Quantum transducers play a crucial role in hybrid quantum networks. A good
      quantum transducer can faithfully convert quantum signals from one mode to
      another with minimum decoherence. Most investigations of quantum transduction are
      based on the protocol of direct mode conversion. However, the direct protocol
      requires the matching condition, which in practice is not always feasible. Here
      we propose an adaptive protocol for quantum transducers, which can convert
      quantum signals without requiring the matching condition. The adaptive protocol
      only consists of Gaussian operations, feasible in various physical platforms.
      Moreover, we show that the adaptive protocol can be robust against imperfections
      associated with finite squeezing, thermal noise, and homodyne detection, and it
      can be implemented to realize quantum state transfer between microwave and
      optical modes.

PMID- 29376680
TI  - Exploring Partonic Structure of Hadrons Using ab initio Lattice QCD Calculations.
AB  - Following our previous proposal, we construct a class of good "lattice cross
      sections" (LCSs), from which we can study the partonic structure of hadrons from
      ab initio lattice QCD calculations. These good LCSs, on the one hand, can be
      calculated directly in lattice QCD, and on the other hand, can be factorized into
      parton distribution functions (PDFs) with calculable coefficients, in the same
      way as QCD factorization for factorizable hadronic cross sections. PDFs could be
      extracted from QCD global analysis of the lattice QCD generated data of LCSs. We
      also show that the proposed functions for lattice QCD calculation of PDFs in the
      literature are special cases of these good LCSs.

PMID- 29376681
TI  - Sign Switch of Gaussian Bending Modulus for Microemulsions: A Self-Consistent
      Field Analysis Exploring Scale Invariant Curvature Energies.
AB  - Bending rigidities of tensionless balanced liquid-liquid interfaces as occurring
      in microemulsions are predicted using self-consistent field theory for
      molecularly inhomogeneous systems. Considering geometries with scale invariant
      curvature energies gives unambiguous bending rigidities for systems with fixed
      chemical potentials: the minimal surface Im3m cubic phase is used to find the
      Gaussian bending rigidity kappa[over -], and a torus with Willmore energy
      W=2pi^{2} allows for direct evaluation of the mean bending modulus kappa.
      Consistent with this, the spherical droplet gives access to 2kappa+kappa[over -].
      We observe that kappa[over -] tends to be negative for strong segregation and
      positive for weak segregation, a finding which is instrumental for understanding
      phase transitions from a lamellar to a spongelike microemulsion. Invariably,
      kappa remains positive and increases with increasing strength of segregation.

PMID- 29376676
TI  - Spin Dependence of eta Meson Production in Proton-Proton Collisions Close to
      Threshold.
AB  - Taking advantage of the high acceptance and axial symmetry of the WASA-at-COSY
      detector, and the high polarization degree of the proton beam of COSY, the
      reaction p[over ->]p->ppeta has been measured close to threshold to explore the
      analyzing power A_{y}. The angular distribution of A_{y} is determined with the
      precision improved by more than 1 order of magnitude with respect to previous
      results, allowing a first accurate comparison with theoretical predictions. The
      determined analyzing power is consistent with zero for an excess energy of Q=15 
      MeV, signaling s-wave production with no evidence for higher partial waves. At
      Q=72  MeV the data reveal strong interference of Ps and Pp partial waves and
      cancellation of (Pp)^{2} and Ss^{*}Sd contributions. These results rule out the
      presently available theoretical predictions for the production mechanism of the
      eta meson.

PMID- 29376682
TI  - Stable Liquid Jets Bouncing off Soft Gels.
AB  - A liquid jet can stably bounce off a sufficiently soft gel by following the
      contour of the dimple created upon impact. This new phenomenon is insensitive to
      the wetting properties of the gels and was observed for different liquids over a
      wide range of surface tensions, gamma=24-72  mN/m. In contrast, other jet rebound
      phenomena are typically sensitive to gamma: only a high gamma jet rebounds off a
      hard solid (e.g. superhydrophobic surface) and only a low gamma jet bounces off a
      liquid bath. This is because an air layer must be stabilized between the two
      interfaces. For a soft gel, no air layer is necessary and the jet rebound remains
      stable even when there is direct liquid-gel contact.

PMID- 29376683
TI  - Exploring Zeptosecond Quantum Equilibration Dynamics: From Deep-Inelastic to
      Fusion-Fission Outcomes in ^{58}Ni+^{60}Ni Reactions.
AB  - Energy dissipative processes play a key role in how quantum many-body systems
      dynamically evolve toward equilibrium. In closed quantum systems, such processes
      are attributed to the transfer of energy from collective motion to single
      particle degrees of freedom; however, the quantum many-body dynamics of this
      evolutionary process is poorly understood. To explore energy dissipative
      phenomena and equilibration dynamics in one such system, an experimental
      investigation of deep-inelastic and fusion-fission outcomes in the
      ^{58}Ni+^{60}Ni reaction has been carried out. Experimental outcomes have been
      compared to theoretical predictions using time dependent Hartree-Fock and time
      dependent random phase approximation approaches, which, respectively, incorporate
      one-body energy dissipation and fluctuations. Excellent quantitative agreement
      has been found between experiment and calculations, indicating that microscopic
      models incorporating one-body dissipation and fluctuations provide a potential
      tool for exploring dissipation in low-energy heavy ion collisions.

PMID- 29376684
TI  - Incoherent Qubit Control Using the Quantum Zeno Effect.
AB  - The quantum Zeno effect is the suppression of Hamiltonian evolution by repeated
      observation, which pins the system to an eigenstate of the measurement
      observable. Using measurement alone, control of the state can be achieved if the
      observable is slowly varied, so that the state tracks the now time-dependent
      eigenstate. We demonstrate this using a circuit-QED readout technique that
      couples to a dynamically controllable observable of a qubit. Continuous
      monitoring of the measurement record allows us to detect an escape from the
      eigenstate, thus serving as a built-in form of error detection. We show this by
      postselecting on realizations with high fidelity with respect to the target
      state. Our dynamical measurement operator technique offers a new tool for
      numerous forms of quantum feedback protocols, including adaptive measurements and
      rapid state purification.

PMID- 29376685
TI  - Erratum: Measurement of Body-Centered-Cubic Aluminum at 475 GPa [Phys. Rev. Lett.
      119, 175702 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.175702.

PMID- 29376686
TI  - Connecting Dissipation and Phase Slips in a Josephson Junction between Fermionic
      Superfluids.
AB  - We study the emergence of dissipation in an atomic Josephson junction between
      weakly coupled superfluid Fermi gases. We find that vortex-induced phase slippage
      is the dominant microscopic source of dissipation across the Bose-Einstein
      condensate-Bardeen-Cooper-Schrieffer crossover. We explore different dynamical
      regimes by tuning the bias chemical potential between the two superfluid
      reservoirs. For small excitations, we observe dissipation and phase coherence to
      coexist, with a resistive current followed by well-defined Josephson
      oscillations. We link the junction transport properties to the phase-slippage
      mechanism, finding that vortex nucleation is primarily responsible for the
      observed trends of conductance and critical current. For large excitations, we
      observe the irreversible loss of coherence between the two superfluids, and
      transport cannot be described only within an uncorrelated phase-slip picture. Our
      findings open new directions for investigating the interplay between dissipative
      and superfluid transport in strongly correlated Fermi systems, and general
      concepts in out-of-equilibrium quantum systems.

PMID- 29376687
TI  - Quantum States with a Positive Partial Transpose are Useful for Metrology.
AB  - We show that multipartite quantum states that have a positive partial transpose
      with respect to all bipartitions of the particles can outperform separable states
      in linear interferometers. We introduce a powerful iterative method to find such
      states. We present some examples for multipartite states and examine the scaling
      of the precision with the particle number. Some bipartite examples are also shown
      that possess an entanglement very robust to noise. We also discuss the relation
      of metrological usefulness to Bell inequality violation. We find that quantum
      states that do not violate any Bell inequality can outperform separable states
      metrologically. We present such states with a positive partial transpose, as well
      as with a nonpositive partial transpose.

PMID- 29376688
TI  - Chaotic Properties of a Turbulent Isotropic Fluid.
AB  - By tracking the divergence of two initially close trajectories in phase space in
      an Eulerian approach to forced turbulence, the relation between the maximal
      Lyapunov exponent lambda and the Reynolds number Re is measured using direct
      numerical simulations, performed on up to 2048^{3} collocation points. The
      Lyapunov exponent is found to solely depend on the Reynolds number with
      lambda?Re^{0.53} and that after a transient period the divergence of trajectories
      grows at the same rate at all scales. Finally a linear divergence is seen that is
      dependent on the energy forcing rate. Links are made with other chaotic systems.

PMID- 29376689
TI  - Direct Measurement of the Surface Energy of Bimetallic Nanoparticles: Evidence of
      Vegard's Rulelike Dependence.
AB  - We use in situ transmission electron microscopy to monitor in real time the
      evaporation of gold, copper, and bimetallic copper-gold nanoparticles at high
      temperature. Besides, we extend the Kelvin equation to two-component systems to
      predict the evaporation rates of spherical liquid mono- and bimetallic
      nanoparticles. By linking this macroscopic model to experimental TEM data, we
      determine the surface energies of pure gold, pure copper, Cu_{50}Au_{50}, and
      Cu_{25}Au_{75} nanoparticles in the liquid state. Our model suggests that the
      surface energy varies linearly with the composition in the liquid Cu-Au
      nanoalloy; i.e., it follows a Vegard's rulelike dependence. To get atomic-scale
      insights into the thermodynamic properties of Cu-Au alloys on the whole
      composition range, we perform Monte Carlo simulations employing N-body
      interatomic potentials. These simulations at a microscopic level confirm the
      Vegard's rulelike behavior of the surface energy obtained from experiments
      combined with macroscopic modeling.

PMID- 29376690
TI  - On-the-Fly Machine Learning of Atomic Potential in Density Functional Theory
      Structure Optimization.
AB  - Machine learning (ML) is used to derive local stability information for density
      functional theory calculations of systems in relation to the recently discovered
      SnO_{2}(110)-(4*1) reconstruction. The ML model is trained on (structure, total
      energy) relations collected during global minimum energy search runs with an
      evolutionary algorithm (EA). While being built, the ML model is used to guide the
      EA, thereby speeding up the overall rate by which the EA succeeds. Inspection of
      the local atomic potentials emerging from the model further shows chemically
      intuitive patterns.

PMID- 29376691
TI  - Velocity Gradient Power Functional for Brownian Dynamics.
AB  - We present an explicit and simple approximation for the superadiabatic excess
      (over ideal gas) free power functional, admitting the study of the nonequilibrium
      dynamics of overdamped Brownian many-body systems. The functional depends on the
      local velocity gradient and is systematically obtained from treating the
      microscopic stress distribution as a conjugate field. The resulting
      superadiabatic forces are beyond dynamical density functional theory and are of a
      viscous nature. Their high accuracy is demonstrated by comparison to simulation
      results.

PMID- 29376675
TI  - Nuclear Dependence of the Transverse-Single-Spin Asymmetry for Forward Neutron
      Production in Polarized p+A Collisions at sqrt[s_{NN}]=200  GeV.
AB  - During 2015, the Relativistic Heavy Ion Collider (RHIC) provided collisions of
      transversely polarized protons with Au and Al nuclei for the first time, enabling
      the exploration of transverse-single-spin asymmetries with heavy nuclei. Large
      single-spin asymmetries in very forward neutron production have been previously
      observed in transversely polarized p+p collisions at RHIC, and the existing
      theoretical framework that was successful in describing the single-spin asymmetry
      in p+p collisions predicts only a moderate atomic-mass-number (A) dependence. In
      contrast, the asymmetries observed at RHIC in p+A collisions showed a
      surprisingly strong A dependence in inclusive forward neutron production. The
      observed asymmetry in p+Al collisions is much smaller, while the asymmetry in
      p+Au collisions is a factor of 3 larger in absolute value and of opposite sign.
      The interplay of different neutron production mechanisms is discussed as a
      possible explanation of the observed A dependence.

PMID- 29376692
TI  - Spectrum Estimation of Density Operators with Alkaline-Earth Atoms.
AB  - We show that Ramsey spectroscopy of fermionic alkaline-earth atoms in a square
      well trap provides an efficient and accurate estimate for the eigenspectrum of a
      density matrix whose n copies are stored in the nuclear spins of n such atoms.
      This spectrum estimation is enabled by the high symmetry of the interaction
      Hamiltonian, dictated, in turn, by the decoupling of the nuclear spin from the
      electrons and by the shape of the square-well trap. Practical performance of this
      procedure and its potential applications to quantum computing and time keeping
      with alkaline-earth atoms are discussed.

PMID- 29376693
TI  - Ultracold Heteronuclear Three-Body Systems: How Diabaticity Limits the
      Universality of Recombination into Shallow Dimers.
AB  - The mass-imbalanced three-body recombination process that forms a shallow dimer
      is shown to possess a rich Efimov-Stuckelberg landscape, with corresponding
      spectra that differ fundamentally from the homonuclear case. A semianalytical
      treatment of the three-body recombination predicts unusual spectra with
      intertwined resonance peaks and minima and yields in-depth insight into the
      behavior of the corresponding Efimov spectra. In particular, the patterns of the
      Efimov-Stuckelberg landscape are shown to depend inherently on the degree of
      diabaticity of the three-body collisions, which strongly affects the universality
      of the heteronuclear Efimov states.

PMID- 29376694
TI  - Mean-Potential Law in Evolutionary Games.
AB  - The Letter presents a novel way to connect random walks, stochastic differential
      equations, and evolutionary game theory. We introduce a new concept of a
      potential function for discrete-space stochastic systems. It is based on a
      correspondence between one-dimensional stochastic differential equations and
      random walks, which may be exact not only in the continuous limit but also in
      finite-state spaces. Our method is useful for computation of fixation
      probabilities in discrete stochastic dynamical systems with two absorbing states.
      We apply it to evolutionary games, formulating two simple and intuitive criteria
      for evolutionary stability of pure Nash equilibria in finite populations. In
      particular, we show that the 1/3 law of evolutionary games, introduced by Nowak
      et al. [Nature, 2004], follows from a more general mean-potential law.

PMID- 29376695
TI  - Defect in the Joint Spectrum of Hydrogen due to Monodromy.
AB  - In addition to the well-known case of spherical coordinates, the Schrodinger
      equation of the hydrogen atom separates in three further coordinate systems.
      Separating in a particular coordinate system defines a system of three commuting
      operators. We show that the joint spectrum of the Hamilton operator, the z
      component of the angular momentum, and an operator involving the z component of
      the quantum Laplace-Runge-Lenz vector obtained from separation in prolate
      spheroidal coordinates has quantum monodromy for energies sufficiently close to
      the ionization threshold. The precise value of the energy above which monodromy
      is observed depends on the distance of the focus points of the spheroidal
      coordinates. The presence of monodromy means that one cannot globally assign
      quantum numbers to the joint spectrum. Whereas the principal quantum number n and
      the magnetic quantum number m correspond to the Bohr-Sommerfeld quantization of
      globally defined classical actions a third quantum number cannot be globally
      defined because the third action is globally multivalued.

PMID- 29376696
TI  - Light-Cone and Diffusive Propagation of Correlations in a Many-Body Dissipative
      System.
AB  - We analyze the propagation of correlations after a sudden interaction change in a
      strongly interacting quantum system in contact with an environment. In
      particular, we consider an interaction quench in the Bose-Hubbard model, deep
      within the Mott-insulating phase, under the effect of dephasing. We observe that
      dissipation effectively speeds up the propagation of single-particle correlations
      while reducing their coherence. In contrast, for two-point density correlations,
      the initial ballistic propagation regime gives way to diffusion at intermediate
      times. Numerical simulations, based on a time-dependent matrix product state
      algorithm, are supplemented by a quantitatively accurate fermionic quasiparticle
      approach providing an intuitive description of the initial dynamics in terms of
      holon and doublon excitations.

PMID- 29376697
TI  - Raman Amplification with a Flying Focus.
AB  - We propose a new laser amplifier scheme utilizing stimulated Raman scattering in
      plasma in conjunction with a "flying focus"-a chromatic focusing system combined
      with a chirped pump beam that provides spatiotemporal control over the pump's
      focal spot. Pump intensity isosurfaces are made to propagate at v=-c so as to be
      in sync with the injected counterpropagating seed pulse. By setting the pump
      intensity in the interaction region to be just above the ionization threshold of
      the background gas, an ionization wave is produced that travels at a fixed
      distance ahead of the seed. Simulations show that this will make it possible to
      optimize the plasma temperature and mitigate many of the issues that are known to
      have impacted previous Raman amplification experiments, in particular, the growth
      of precursors.

PMID- 29376698
TI  - Measurement of Preheat Due to Nonlocal Electron Transport in Warm Dense Matter.
AB  - This Letter presents a novel approach to study electron transport in warm dense
      matter. It also includes the first x-ray Thomson scattering (XRTS) measurement
      from low-density CH foams compressed by a strong laser-driven shock at the OMEGA
      laser facility. The XRTS measurement is combined with velocity interferometry
      (VISAR) and optical pyrometry (SOP) providing a robust measurement of
      thermodynamic conditions in the shock. Evidence of significant preheat
      contributing to elevated temperatures reaching 17.5-35 eV in shocked CH foam is
      measured by XRTS. These measurements are complemented by abnormally high shock
      velocities observed by VISAR and early emission seen by SOP. These results are
      compared to radiation hydrodynamics simulations that include first-principles
      treatment of nonlocal electron transport in warm dense matter with excellent
      agreement. Additional simulations confirm that the x-ray contribution to this
      preheat is negligible.

PMID- 29376699
TI  - Longitudinal Negative Magnetoresistance and Magnetotransport Phenomena in
      Conventional and Topological Conductors.
AB  - Recently, a large negative longitudinal (parallel to the magnetic field)
      magnetoresistance was observed in Weyl and Dirac semimetals. It is believed to be
      related to the chiral anomaly associated with topological electron band structure
      of these materials. We show that in a certain range of parameters such a
      phenomenon can also exist in conventional centrosymmetric and time-reversal
      invariant conductors, lacking topological protection of the electron spectrum and
      the chiral anomaly. We also discuss the magnetic field enhancement of the
      longitudinal components of the thermal conductivity and thermoelectric tensors.

PMID- 29376700
TI  - Topological Nodal-Net Semimetal in a Graphene Network Structure.
AB  - Topological semimetals are characterized by the nodal points in their electronic
      structure near the Fermi level, either discrete or forming a continuous line or
      ring, which are responsible for exotic properties related to the topology of bulk
      bands. Here we identify by ab initio calculations a distinct topological
      semimetal that exhibits nodal nets comprising multiple interconnected nodal lines
      in bulk and have two coupled drumheadlike flat bands around the Fermi level on
      its surface. This nodal net semimetal state is proposed to be realized in a
      graphene network structure that can be constructed by inserting a benzene ring
      into each C?C bond in the bct-C_{4} lattice or by a crystalline modification of
      the (5,5) carbon nanotube. These results expand the realm of nodal manifolds in
      topological semimetals, offering a new platform for exploring novel physics in
      these fascinating materials.

PMID- 29376701
TI  - Analysis of the Daya Bay Reactor Antineutrino Flux Changes with Fuel Burnup.
AB  - We investigate the recent Daya Bay results on the changes in the antineutrino
      flux and spectrum with the burnup of the reactor fuel. We find that the
      discrepancy between current model predictions and the Daya Bay results can be
      traced to the original measured ^{235}U/^{239}Pu ratio of the fission beta
      spectra that were used as a base for the expected antineutrino fluxes. An
      analysis of the antineutrino spectra that is based on a summation over all
      fission fragment beta decays, using nuclear database input, explains all of the
      features seen in the Daya Bay evolution data. However, this summation method
      still allows for an anomaly. We conclude that there is currently not enough
      information to use the antineutrino flux changes to rule out the possible
      existence of sterile neutrinos.

PMID- 29376702
TI  - Surfactant Variations in Porous Media Localize Capillary Instabilities during
      Haines Jumps.
AB  - We use confocal microscopy to measure velocity and interfacial tension between a
      trapped wetting phase with a surfactant and a flowing, invading nonwetting phase
      in a porous medium. We relate interfacial tension variations at the fluid-fluid
      interface to surfactant concentration and show that these variations localize the
      destabilization of capillary forces and lead to rapid local invasion of the
      nonwetting fluid, resulting in a Haines jump. These spatial variations in
      surfactant concentration are caused by velocity variations at the fluid-fluid
      interfaces and lead to localization of the Haines jumps even in otherwise very
      uniform pore structure and pressure conditions. Our results provide new insight
      into the nature of Haines jumps, one of the most ubiquitous and important
      instabilities in flow in porous media.

PMID- 29376704
TI  - Thermal Dark Matter Below a MeV.
AB  - We consider a class of models in which thermal dark matter is lighter than a MeV.
      If dark matter thermalizes with the standard model below the temperature of
      neutrino-photon decoupling, equilibration and freeze-out cool and heat the
      standard model bath comparably, alleviating constraints from measurements of the
      effective number of neutrino species. We demonstrate this mechanism in a model
      consisting of fermionic dark matter coupled to a light scalar mediator. Thermal
      dark matter can be as light as a few keV, while remaining compatible with
      existing cosmological and astrophysical observations. This framework motivates
      new experiments in the direct search for sub-MeV thermal dark matter and light
      force carriers.

PMID- 29376705
TI  - Towards Device-Independent Information Processing on General Quantum Networks.
AB  - The violation of certain Bell inequalities allows for device-independent
      information processing secure against nonsignaling eavesdroppers. However, this
      only holds for the Bell network, in which two or more agents perform local
      measurements on a single shared source of entanglement. To overcome the practical
      constraints that entangled systems can only be transmitted over relatively short
      distances, large-scale multisource networks have been employed. Do there exist
      analogs of Bell inequalities for such networks, whose violation is a resource for
      device independence? In this Letter, the violation of recently derived polynomial
      Bell inequalities will be shown to allow for device independence on multisource
      networks, secure against nonsignaling eavesdroppers.

PMID- 29376703
TI  - Soft X-Ray Second Harmonic Generation as an Interfacial Probe.
AB  - Nonlinear optical processes at soft x-ray wavelengths have remained largely
      unexplored due to the lack of available light sources with the requisite
      intensity and coherence. Here we report the observation of soft x-ray second
      harmonic generation near the carbon K edge (~284  eV) in graphite thin films
      generated by high intensity, coherent soft x-ray pulses at the FERMI free
      electron laser. Our experimental results and accompanying first-principles
      theoretical analysis highlight the effect of resonant enhancement above the
      carbon K edge and show the technique to be interfacially sensitive in a
      centrosymmetric sample with second harmonic intensity arising primarily from the
      first atomic layer at the open surface. This technique and the associated
      theoretical framework demonstrate the ability to selectively probe interfaces,
      including those that are buried, with elemental specificity, providing a new tool
      for a range of scientific problems.

PMID- 29376706
TI  - Edge Modes and Nonlocal Conductance in Graphene Superlattices.
AB  - We study the existence of edge modes in gapped moire superlattices of graphene
      monolayer ribbons on a hexagonal boron nitride substrate. We find that the
      superlattice bands acquire finite Chern numbers, which lead to a valley Hall
      effect. The presence of dispersive edge modes is confirmed by calculations of the
      band structure of realistic nanoribbons using tight binding methods. These edge
      states are only weakly sensitive to disorder, as short-range scattering processes
      lead to mean free paths of the order of microns. The results explain the
      existence of edge currents when the chemical potential lies within the bulk
      superlattice gap, and offer an explanation for existing nonlocal resistivity
      measurements in graphene ribbons on boron nitride.

PMID- 29376707
TI  - Inner Phases of Colloidal Hexagonal Spin Ice.
AB  - Using numerical simulations that mimic recent experiments on hexagonal colloidal
      ice, we show that colloidal hexagonal artificial spin ice exhibits an inner phase
      within its ice state that has not been observed previously. Under increasing
      colloid-colloid repulsion, the initially paramagnetic system crosses into a
      disordered ice regime, then forms a topologically charge ordered state with
      disordered colloids, and finally reaches a threefold degenerate, ordered
      ferromagnetic state. This is reminiscent of, yet distinct from, the inner phases
      of the magnetic kagome spin ice analog. The difference in the inner phases of the
      two systems is explained by their difference in energetics and frustration.

PMID- 29376708
TI  - Measuring Anomalous Heating in a Planar Ion Trap with Variable Ion-Surface
      Separation.
AB  - Cold ions trapped in the vicinity of conductive surfaces experience heating of
      their oscillatory motion. Typically, the rate of this heating is orders of
      magnitude larger than expected from electric field fluctuations due to thermal
      motion of electrons in the conductors. This effect, known as anomalous heating,
      is not fully understood. One of the open questions is the heating rate's
      dependence on the ion-electrode separation. We present a direct measurement of
      this dependence in an ion trap of simple planar geometry. The heating rates are
      determined by taking images of a single ^{172}Yb^{+} ion's resonance fluorescence
      after a variable heating time and deducing the trapped ion's temperature from
      measuring its average oscillation amplitude. Assuming a power law for the heating
      rate versus ion-surface separation dependence, an exponent of -3.79+/-0.12 is
      measured.

PMID- 29376709
TI  - First-Principles Prediction of New Electrides with Nontrivial Band Topology Based
      on One-Dimensional Building Blocks.
AB  - We introduce a new class of electrides with nontrivial band topology by coupling
      materials database searches and first-principles-calculations-based analysis.
      Cs_{3}O and Ba_{3}N are for the first time identified as a new class of
      electrides, consisting of one-dimensional (1D) nanorod building blocks. Their
      crystal structures mimic beta-TiCl_{3} with the position of anions and cations
      exchanged. Unlike the weakly coupled nanorods of beta-TiCl_{3}, Cs_{3}O and
      Ba_{3}N retain 1D anionic electrons along the hollow interrod sites;
      additionally, a strong interrod interaction in C_{3}O and Ba_{3}N induces band
      inversion in a 2D superatomic triangular lattice, resulting in Dirac-node lines.
      The new class of electrides can serve as a prototype for new electrides with a
      large cavity space that can be utilized for various applications such as gas
      storage, ion transport, and metal intercalation.

PMID- 29376710
TI  - Robust 2-Qubit Gates in a Linear Ion Crystal Using a Frequency-Modulated Driving
      Force.
AB  - In an ion trap quantum computer, collective motional modes are used to entangle
      two or more qubits in order to execute multiqubit logical gates. Any residual
      entanglement between the internal and motional states of the ions results in loss
      of fidelity, especially when there are many spectator ions in the crystal. We
      propose using a frequency-modulated driving force to minimize such errors. In
      simulation, we obtained an optimized frequency-modulated 2-qubit gate that can
      suppress errors to less than 0.01% and is robust against frequency drifts over +/
      1  kHz. Experimentally, we have obtained a 2-qubit gate fidelity of 98.3(4)%, a
      state-of-the-art result for 2-qubit gates with five ions.

PMID- 29376711
TI  - Voltage Control of Rare-Earth Magnetic Moments at the Magnetic-Insulator-Metal
      Interface.
AB  - The large spin-orbit interaction in the lanthanides implies a strong coupling
      between their internal charge and spin degrees of freedom. We formulate the
      coupling between the voltage and the local magnetic moments of rare-earth atoms
      with a partially filled 4f shell at the interface between an insulator and a
      metal. The rare-earth-mediated torques allow the power-efficient control of
      spintronic devices by electric-field-induced ferromagnetic resonance and
      magnetization switching.

PMID- 29376712
TI  - Publisher's Note: Measurement of Singly Cabibbo Suppressed Decays Lambda_{c}^{+}
      >ppi^{+}pi^{-} and Lambda_{c}^{+}->pK^{+}K^{-} [Phys. Rev. Lett. 117, 232002
      (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.232002.

PMID- 29376713
TI  - Switching of Magnons by Electric and Magnetic Fields in Multiferroic Borates.
AB  - Electric manipulation of magnetic properties is a key problem of materials
      research. To fulfill the requirements of modern electronics, these processes must
      be shifted to high frequencies. In multiferroic materials, this may be achieved
      by electric and magnetic control of their fundamental excitations. Here we
      identify magnetic vibrations in multiferroic iron borates that are simultaneously
      sensitive to external electric and magnetic fields. Nearly 100% modulation of the
      terahertz radiation in an external field is demonstrated for
      SmFe_{3}(BO_{3})_{4}. High sensitivity can be explained by a modification of the
      spin orientation that controls the excitation conditions in multiferroic borates.
      These experiments demonstrate the possibility to alter terahertz magnetic
      properties of materials independently by external electric and magnetic fields.

PMID- 29376714
TI  - Nonlinear Large Scale Flow in a Precessing Cylinder and Its Ability To Drive
      Dynamo Action.
AB  - We have conducted experimental measurements and numerical simulations of a
      precession-driven flow in a cylindrical cavity. The study is dedicated to the
      precession dynamo experiment currently under construction at Helmholtz-Zentrum
      Dresden-Rossendorf and aims at the evaluation of the hydrodynamic flow with
      respect to its ability to drive a dynamo. We focus on the strongly nonlinear
      regime in which the flow is essentially composed of the directly forced primary
      Kelvin mode and higher modes in terms of standing inertial waves arising from
      nonlinear self-interactions. We obtain an excellent agreement between experiment
      and simulation with regard to both flow amplitudes and flow geometry. A
      peculiarity is the resonance-like emergence of an axisymmetric mode that
      represents a double roll structure in the meridional plane. Kinematic simulations
      of the magnetic field evolution induced by the time-averaged flow yield dynamo
      action at critical magnetic Reynolds numbers around Rm^{c}~430, which is well
      within the range of the planned liquid sodium experiment.

PMID- 29376715
TI  - Model-Free Prediction of Large Spatiotemporally Chaotic Systems from Data: A
      Reservoir Computing Approach.
AB  - We demonstrate the effectiveness of using machine learning for model-free
      prediction of spatiotemporally chaotic systems of arbitrarily large spatial
      extent and attractor dimension purely from observations of the system's past
      evolution. We present a parallel scheme with an example implementation based on
      the reservoir computing paradigm and demonstrate the scalability of our scheme
      using the Kuramoto-Sivashinsky equation as an example of a spatiotemporally
      chaotic system.

PMID- 29376716
TI  - Higher-Order Topological Insulators and Semimetals on the Breathing Kagome and
      Pyrochlore Lattices.
AB  - A second-order topological insulator in d dimensions is an insulator which has no
      d-1 dimensional topological boundary states but has d-2 dimensional topological
      boundary states. It is an extended notion of the conventional topological
      insulator. Higher-order topological insulators have been investigated in square
      and cubic lattices. In this Letter, we generalize them to breathing kagome and
      pyrochlore lattices. First, we construct a second-order topological insulator on
      the breathing Kagome lattice. Three topological boundary states emerge at the
      corner of the triangle, realizing a 1/3 fractional charge at each corner. Second,
      we construct a third-order topological insulator on the breathing pyrochlore
      lattice. Four topological boundary states emerge at the corners of the
      tetrahedron with a 1/4 fractional charge at each corner. These higher-order
      topological insulators are characterized by the quantized polarization, which
      constitutes the bulk topological index. Finally, we study a second-order
      topological semimetal by stacking the breathing kagome lattice.

PMID- 29376717
TI  - Mean-Field Scenario for the Athermal Creep Dynamics of Yield-Stress Fluids.
AB  - We develop a theoretical description based on an existent mean-field model for
      the transient dynamics prior to the steady flow of yielding materials. The mean
      field model not only reproduces the experimentally observed nonlinear time
      dependence of the shear-rate response to an external stress, but also allows for
      the determination of the different physical processes involved in the onset of
      the reacceleration phase after the initial slowing down and a distinct
      fluidization phase. The fluidization time displays a power-law dependence on the
      distance of the applied stress to an age-dependent yield stress, which is not
      universal but strongly dependent on initial conditions.

PMID- 29376719
TI  - Phase Diagram of Hydrogen and a Hydrogen-Helium Mixture at Planetary Conditions
      by Quantum Monte Carlo Simulations.
AB  - Understanding planetary interiors is directly linked to our ability of simulating
      exotic quantum mechanical systems such as hydrogen (H) and hydrogen-helium (H-He)
      mixtures at high pressures and temperatures. Equation of state (EOS) tables based
      on density functional theory are commonly used by planetary scientists, although
      this method allows only for a qualitative description of the phase diagram. Here
      we report quantum Monte Carlo (QMC) molecular dynamics simulations of pure H and
      H-He mixture. We calculate the first QMC EOS at 6000 K for a H-He mixture of a
      protosolar composition, and show the crucial influence of He on the H
      metallization pressure. Our results can be used to calibrate other EOS
      calculations and are very timely given the accurate determination of Jupiter's
      gravitational field from the NASA Juno mission and the effort to determine its
      structure.

PMID- 29376718
TI  - Enhanced Control and Reproducibility of Non-Neutral Plasmas.
AB  - The simultaneous control of the density and particle number of non-neutral
      plasmas confined in Penning-Malmberg traps is demonstrated. Control is achieved
      by setting the plasma's density by applying a rotating electric field while
      simultaneously fixing its axial potential via evaporative cooling. This novel
      method is particularly useful for stabilizing positron plasmas, as the procedures
      used to collect positrons from radioactive sources typically yield plasmas with
      variable densities and particle numbers; it also simplifies optimization studies
      that require plasma parameter scans. The reproducibility achieved by applying
      this technique to the positron and electron plasmas used by the ALPHA
      antihydrogen experiment at CERN, combined with other developments, contributed to
      a 10-fold increase in the antiatom trapping rate.

PMID- 29376720
TI  - Electromagnon with Sensitive Terahertz Magnetochromism in a Room-Temperature
      Magnetoelectric Hexaferrite.
AB  - An electromagnon in the magnetoelectric (ME) hexaferrite
      Ba_{0.5}Sr_{2.5}Co_{2}Fe_{24}O_{41} (Co_{2}Z-type) single crystal is identified
      by time-domain terahertz (THz) spectroscopy. The associated THz resonance is
      active on the electric field (E^{omega}) of the THz light parallel to the c axis
      (? [001]), whose spectral weight develops at a markedly high temperature,
      coinciding with a transverse conical magnetic order below 410 K. The resonance
      frequency of 1.03 THz at 20 K changes -8.7% and +5.8% under external magnetic
      field (H) of 2 kOe along [001] and [120], respectively. A model Hamiltonian
      describing the conical magnetic order elucidates that the dynamical ME effect
      arises from antiphase motion of spins which are coupled with modulating electric
      dipoles through the exchange striction mechanism. Moreover, the calculated
      frequency shift points to the key role of the Dzyaloshinskii-Moriya interaction
      that is altered by static electric polarization change under different H.

PMID- 29376721
TI  - Lossless Brownian Information Engine.
AB  - We report on a lossless information engine that converts nearly all available
      information from an error-free feedback protocol into mechanical work. Combining
      high-precision detection at a resolution of 1 nm with ultrafast feedback control,
      the engine is tuned to extract the maximum work from information on the position
      of a Brownian particle. We show that the work produced by the engine achieves a
      bound set by a generalized second law of thermodynamics, demonstrating for the
      first time the sharpness of this bound. We validate a generalized Jarzynski
      equality for error-free feedback-controlled information engines.

PMID- 29376722
TI  - Erratum: Optimal Continuous Variable Quantum Teleportation with Limited Resources
      [Phys. Rev. Lett. 119, 120503 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.120503.

PMID- 29376723
TI  - Unraveling the Role of Order-to-Disorder Transition in Shear Thickening
      Suspensions.
AB  - Using high-resolution in situ small angle x-ray scattering in conjunction with
      oscillatory shear on highly monodisperse silica suspensions, we demonstrate that
      an order-to-disorder transition leads to a dynamic shear thickening in a lower
      stress regime than the standard steady shear thickening. We show that the order
      to-disorder transition is controlled by strain, which is distinguishably
      different from steady shear thickening, which is a stress-related phenomenon. The
      appearance of this two-step shear thinning and thickening transition is also
      influenced by the particle size, monodispersity, and measurement conditions
      (i.e., oscillatory shear versus steady shear). Our results show definitively that
      the order-to-disorder transition-induced thickening is completely unrelated to
      the mechanism that drives steady shear thickening.

PMID- 29376724
TI  - Imaging Correlations in Heterodyne Spectra for Quantum Displacement Sensing.
AB  - The extraordinary sensitivity of the output field of an optical cavity to small
      quantum-scale displacements has led to breakthroughs such as the first detection
      of gravitational waves and of the motions of quantum ground-state cooled
      mechanical oscillators. While heterodyne detection of the output optical field of
      an optomechanical system exhibits asymmetries which provide a key signature that
      the mechanical oscillator has attained the quantum regime, important quantum
      correlations are lost. In turn, homodyning can detect quantum squeezing in an
      optical quadrature but loses the important sideband asymmetries. Here we
      introduce and experimentally demonstrate a new technique, subjecting the
      autocorrelators of the output current to filter functions, which restores the
      lost heterodyne correlations (whether classical or quantum), drastically
      augmenting the useful information accessible. The filtering even adjusts for
      moderate errors in the locking phase of the local oscillator. Hence we
      demonstrate the single-shot measurement of hundreds of different field
      quadratures allowing the rapid imaging of detailed features from a simple
      heterodyne trace. We also obtain a spectrum of hybrid homodyne-heterodyne
      character, with motional sidebands of combined amplitudes comparable to homodyne.
      Although investigated here in a thermal regime, the method's robustness and
      generality represents a promising new approach to sensing of quantum-scale
      displacements.

PMID- 29376725
TI  - Space-Group Symmetries Generate Chaotic Fluid Advection in Crystalline Granular
      Media.
AB  - The classical connection between symmetry breaking and the onset of chaos in
      dynamical systems harks back to the seminal theory of Noether [Transp. Theory
      Statist. Phys. 1, 186 (1918)10.1080/00411457108231446]. We study the Lagrangian
      kinematics of steady 3D Stokes flow through simple cubic and body-centered cubic
      (bcc) crystalline lattices of close-packed spheres, and uncover an important
      exception. While breaking of point-group symmetries is a necessary condition for
      chaotic mixing in both lattices, a further space-group (glide) symmetry of the
      bcc lattice generates a transition from globally regular to globally chaotic
      dynamics. This finding provides new insights into chaotic mixing in porous media
      and has significant implications for understanding the impact of symmetries upon
      generic dynamical systems.

PMID- 29376726
TI  - Evidence for Spin Singlet Pairing with Strong Uniaxial Anisotropy in
      URu_{2}Si_{2} Using Nuclear Magnetic Resonance.
AB  - In order to identify the spin contribution to superconducting pairing compatible
      with the so-called "hidden order", ^{29}Si nuclear magnetic resonance
      measurements have been performed using a high-quality single crystal of
      URu_{2}Si_{2}. A clear reduction of the ^{29}Si Knight shift in the
      superconducting state has been observed under a magnetic field applied along the
      crystalline c axis, corresponding to the magnetic easy axis. These results
      provide direct evidence for the formation of spin-singlet Cooper pairs.
      Consequently, results indicating a very tiny change of the in-plane Knight shift
      reported previously demonstrate extreme uniaxial anisotropy for the spin
      susceptibility in the hidden order state.

PMID- 29376728
TI  - Erratum: Quantum Criticality in Resonant Andreev Conduction [Phys. Rev. Lett.
      119, 116802 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.116802.

PMID- 29376727
TI  - First Measurement of the g Factor in the Chiral Band: The Case of the ^{128}Cs
      Isomeric State.
AB  - The g factor of the 56 ns half-life isomeric state in ^{128}Cs has been measured
      using the time-differential perturbed angular distribution method. This state is
      the bandhead of the positive-parity chiral rotational band, which emerges when an
      unpaired proton, an unpaired neutron hole, and an even-even core are coupled such
      that their angular momentum vectors are aplanar (chiral configuration). g-factor
      measurements can give important information on the relative orientation of the
      three angular momentum vectors. The measured g factor g=+0.59(1) shows that there
      is an important contribution of the core rotation in the total angular momentum
      of the isomeric state. Moreover, a quantitative theoretical analysis supports the
      conclusion that the three angular momentum vectors lie almost in one plane, which
      suggests that the chiral configuration in ^{128}Cs demonstrated in previous works
      by characteristic patterns of electromagnetic transitions appears only above some
      value of the total nuclear spin.

PMID- 29376730
TI  - Displacement Operators and Constraints on Boundary Central Charges.
AB  - Boundary conformal field theories have several additional terms in the trace
      anomaly of the stress tensor associated purely with the boundary. We constrain
      the corresponding boundary central charges in three- and four-dimensional
      conformal field theories in terms of two- and three-point correlation functions
      of the displacement operator. We provide a general derivation by comparing the
      trace anomaly with scale dependent contact terms in the correlation functions. We
      conjecture a relation between the a-type boundary charge in three dimensions and
      the stress tensor two-point function near the boundary. We check our results for
      several free theories.

PMID- 29376732
TI  - Visual attention during the evaluation of facial attractiveness is influenced by
      facial angles and smile.
AB  - OBJECTIVE: To examine the changes in visual attention influenced by facial angles
      and smile during the evaluation of facial attractiveness. MATERIALS AND METHODS:
      Thirty-three young adults were asked to rate the overall facial attractiveness
      (task 1 and 3) or to select the most attractive face (task 2) by looking at
      multiple panel stimuli consisting of 0 degrees , 15 degrees , 30 degrees , 45
      degrees , 60 degrees , and 90 degrees  rotated facial photos with or without a
      smile for three model face photos and a self-photo (self-face). Eye gaze and
      fixation time (FT) were monitored by the eye-tracking device during the
      performance. Participants were asked to fill out a subjective questionnaire
      asking, "Which face was primarily looked at when evaluating facial
      attractiveness?" RESULTS: When rating the overall facial attractiveness (task 1)
      for model faces, FT was highest for the 0 degrees  face and lowest for the 90
      degrees  face regardless of the smile ( P < .01). However, when the most
      attractive face was to be selected (task 2), the FT of the 0 degrees  face
      decreased, while it significantly increased for the 45 degrees  face ( P < .001).
      When facial attractiveness was evaluated with the simplified panels combined with
      facial angles and smile (task 3), the FT of the 0 degrees  smiling face was the
      highest ( P < .01). While most participants reported that they looked mainly at
      the 0 degrees  smiling face when rating facial attractiveness, visual attention
      was broadly distributed within facial angles. CONCLUSIONS: Laterally rotated
      faces and presence of a smile highly influence visual attention during the
      evaluation of facial esthetics.

PMID- 29376731
TI  - Paraspinal arteriovenous fistula: Stuttgart classification based on experience
      and a review of the literature.
AB  - The term "paraspinal arteriovenous shunts" (PAVSs) summarizes an inhomogeneous
      variety of rare vascular disorders. PAVSs have been observed as congenital or
      acquired lesions. The clinical course of PAVSs may be asymptomatic or present
      with life-threatening symptoms. Based on a collection of individual cases from
      three institutions and a literature evaluation, we propose the following
      classification: PAVSs that are part of a genetic syndrome are separated from
      "isolated" PAVSs. Isolated PAVSs are subdivided into "acquired", "traumatic" and
      "congenital" without an identifiable genetic hereditary disorder. The subgroups
      are differentiated by the route of venous drainage, being exclusively extraspinal
      or involving intraspinal veins. PAVSs associated to a genetic syndrome may either
      have a metameric link or occur together with a systemic genetic disorder. Again
      extra-vs intraspinal venous drainage is differentiated. The indication for
      treatment is based on individual circumstances (e.g. myelon compression, vascular
      bruit, high volume output cardiac failure). Most PAVSs can be treated by
      endovascular means using detachable coils, liquid embolic agents or stents and
      derivates.

PMID- 29376733
TI  - Primary failure of eruption: Clinical and genetic findings in the mixed
      dentition.
AB  - OBJECTIVE: To test the hypothesis that mutations in the parathyroid hormone 1
      receptor ( PTH1R) include effects in both primary and permanent teeth. MATERIALS
      AND METHODS: DNA was extracted from saliva samples of 29 patients (8 familial and
      21 sporadic) who presented with clinical evidence of infraoccluded teeth, and
      their unaffected relatives (N = 22). Sequencing followed by mutational analysis
      of the coding regions of PTH1R gene was completed for all individuals (N = 29).
      RESULTS: Eight of 29 cases revealed a heterozygous pathogenic variant in the
      PTH1R gene; five of eight variants represented distinct mutations based on
      comparison with the dbSNP, HGMD, and ESP databases. One mutation (c.1765 T>C
      p.Trp89Arg) was found to segregate within a family (n = 3). In silico analyses
      for all variants revealed a putative pathogenic effect. A genotype-phenotype
      correlation was reported as defined by a functional mutation in PTH1R and
      corresponding effects on one or more posterior teeth only; unilateral or
      bilateral involvement, infraoccluded primary teeth. CONCLUSIONS: Novel mutations
      were reported in the PTH1R gene that included PFE-affected primary molars, thus
      providing the basis for using a genetic diagnostic tool for early diagnosis
      leading to proper management.

PMID- 29376734
TI  - Measuring the effectiveness of patient-chosen reminder methods in a private
      orthodontic practice.
AB  - OBJECTIVE: To evaluate the effectiveness of patient-chosen appointment reminder
      methods (phone call, e-mail, or SMS text) in reducing no-show rates. MATERIALS
      AND METHODS: This was a retrospective case study that determined the correlation
      between patient-chosen appointment reminder methods and no-show rates in a
      private orthodontic practice. This study was conducted in a single office
      location of a multioffice private orthodontic practice using data gathered in
      2015. The subjects were patients who self-selected the appointment reminder
      method (phone call, e-mail, or SMS text). Patient appointment data were collected
      over a 6-month period. Patient attendance was analyzed with descriptive
      statistics to determine any significant differences among patient-chosen reminder
      methods. RESULTS: There was a total of 1193 appointments with an average no-show
      rate of 2.43% across the three reminder methods. No statistically significant
      differences ( P = .569) were observed in the no-show rates between the three
      methods: phone call (3.49%), e-mail (2.68%), and SMS text (1.90%). CONCLUSIONS:
      The electronic appointment reminder methods (SMS text and e-mail) had lower no
      show rates compared with the phone call method, with SMS text having the lowest
      no-show rate of 1.90%. However, since no significant differences were observed
      between the three patient-chosen reminder methods, providers may want to allow
      patients to choose their reminder method to decrease no-shows.

PMID- 29376735
TI  - Adaptive parametric prediction of event times in clinical trials.
AB  - BACKGROUND: In event-based clinical trials, it is common to conduct interim
      analyses at planned landmark event counts. Accurate prediction of the timing of
      these events can support logistical planning and the efficient allocation of
      resources. As the trial progresses, one may wish to use the accumulating data to
      refine predictions. PURPOSE: Available methods to predict event times include
      parametric cure and non-cure models and a nonparametric approach involving
      Bayesian bootstrap simulation. The parametric methods work well when their
      underlying assumptions are met, and the nonparametric method gives calibrated but
      inefficient predictions across a range of true models. In the early stages of a
      trial, when predictions have high marginal value, it is difficult to infer the
      form of the underlying model. We seek to develop a method that will adaptively
      identify the best-fitting model and use it to create robust predictions. METHODS:
      At each prediction time, we repeat the following steps: (1) resample the data;
      (2) identify, from among a set of candidate models, the one with the highest
      posterior probability; and (3) sample from the predictive posterior of the data
      under the selected model. RESULTS: A Monte Carlo study demonstrates that the
      adaptive method produces prediction intervals whose coverage is robust within the
      family of selected models. The intervals are generally wider than those produced
      assuming the correct model, but narrower than nonparametric prediction intervals.
      We demonstrate our method with applications to two completed trials: The
      International Chronic Granulomatous Disease study and Radiation Therapy Oncology
      Group trial 0129. LIMITATIONS: Intervals produced under any method can be badly
      calibrated when the sample size is small and unhelpfully wide when predicting the
      remote future. Early predictions can be inaccurate if there are changes in
      enrollment practices or trends in survival. CONCLUSIONS: An adaptive event-time
      prediction method that selects the model given the available data can give
      improved robustness compared to methods based on less flexible parametric models.

PMID- 29376736
TI  - Estimation of proton density fat fraction of the salivary gland.
AB  - OBJECTIVE: Our first objective was to prove the validity of the six-point Dixon
      method for estimating the proton density fat fraction (PDFF) of the salivary
      gland. The second objective was to estimate the salivary gland PDFF using Dixon
      method to evaluate the pathological conditions. METHODS: At first, 12 volunteers
      underwent two types of sequences: single-voxel magnetic resonance spectroscopy
      and the Dixon method and the PDFFs obtained by the two methods were compared.
      Next, a total of 67 individuals [normal, n = 46; Sjogren's syndrome (SS), n = 11;
      and IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), n = 4, parotitis, n =
      6] were enrolled to estimate the parotid gland (PG) and submandibular gland (SMG)
      PDFF using the Dixon method. RESULTS: This volunteer study demonstrated excellent
      correlation between two methods (R2 = 0.964, slope = 1.05). In the normal group,
      the PG-PDFF was correlated with the weight and body mass index (BMI) (rho = 0.38,
      p = 0.0085; and rho = 0.63, p < 0.0001). The SMG-PDFF was also correlated with
      the weight, BMI, and serum triglyceride (rho = 0.37, p = 0.0067; rho = 0.42, p =
      0.0022; and rho = 0.35, p = 0.024). The PG-PDFF of the SS group (48.2 +/- 15.1%)
      was higher than that of any other groups; however, no significant difference was
      found due to the wide overlap. The SS group (39.0 +/- 26.14%) also had
      significantly higher SMG-PDFF than the normal group (8.9 +/- 5.4%), p < 0.0001)
      and IgG4-DS group (3.8 +/- 2.3%), p = 0.020). CONCLUSION: The Dixon method is a
      feasible method for estimating the PDFF and demonstrates fat accumulation in SMG
      in the SS group. Advances in knowledge: The PDFF obtained by the Dixon method is
      helpful for understanding the salivary gland pathological condition.

PMID- 29376737
TI  - Comparison of the accuracy of periapical radiography with CBCT taken at 3
      different voxel sizes in detecting simulated endodontic complications: an ex vivo
      study.
AB  - OBJECTIVES: To compare the accuracy of a photostimulable phosphor plateP sensor
      with cone beam CT (CBCT) images in the detection of simulated endodontic
      complications. METHODS: Following simulated endodontic complications were created
      in 40 extracted human mandibular molar teeth: Group 1, Instrument separation (N =
      10); Group 2, Strip perforation (N = 10); Group 3, Underfilling of root canals (N
      = 10); Group 4, Overfilling of root canals (N = 10). Intraoral and CBCT images
      (voxel size: 0.075 , 0.1 and 0.2 mm) were taken. Images were scored by 4
      observers according to a 5-point scale. Weighted kappa and intraclass correlation
      coefficients were calculated. Receiveroperating characteristic analysis was
      performed and DeLong test was used to compare areaunder curve values.
      Significance level was set at p < 0.05. RESULTS: Intraobserver kappa ranged from
      moderate (0.417) to excellent (0.918). Intraclass correlation coefficients ranged
      from moderate (0.482) to excellent (0.855). For Group 1 (instrument separation)
      the highest Az values were obtained for intraoral images and the lowest for CBCT
      (0.2 mm voxel size) (p < 0.05). The highest Az values were obtained for Group 2
      (strip perforation) among all groups. With all CBCT image settings, observers
      performed similarly and better than intraoral images (p < 0.05) in detection of
      strip perforation. For Group 3 (underfilling), higher Az values for CBCT images
      were obtained compared to intraoral images without statistically significant
      difference (p > 0.05). For Group 4 (overfilling), higher Az values for CBCT
      images were obtained when compared to digital intraoral for observer 1 and 2 (p <
      0.05). CONCLUSIONS: CBCT images may be useful as an adjunct to periapical imaging
      in the detection of endodontic complications, such as strip perforation and
      overfilled root canals.

PMID- 29376729
TI  - Observation of New Properties of Secondary Cosmic Rays Lithium, Beryllium, and
      Boron by the Alpha Magnetic Spectrometer on the International Space Station.
AB  - We report on the observation of new properties of secondary cosmic rays Li, Be,
      and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV
      with a total of 5.4*10^{6} nuclei collected by AMS during the first five years of
      operation aboard the International Space Station. The Li and B fluxes have an
      identical rigidity dependence above 7 GV and all three fluxes have an identical
      rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0+/-0.1. The three
      fluxes deviate from a single power law above 200 GV in an identical way. This
      behavior of secondary cosmic rays has also been observed in the AMS measurement
      of primary cosmic rays He, C, and O but the rigidity dependences of primary
      cosmic rays and of secondary cosmic rays are distinctly different. In particular,
      above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays.

PMID- 29376738
TI  - An appraisal of moulting on post-moult egg production and egg weight distribution
      in white layer hens; meta-analysis.
AB  - 1. The aim of this study was to establish how different moulting methods and body
      weight losses influenced post-moult performance and USDA egg weight distribution.
      2. Data on 5 laying flocks (#34-38) of the North Carolina Layer Performance and
      Management Test were used in this meta-analysis. 3. The moulting methods were non
      fasted moulted (NF), short feed restricted (SF), 13-d feed restricted (FR), non
      anorexic moult programme (NA), non-anorexic moult programme with low sodium
      (NALS) as well as non-moulting programme as control treatment. The percentages of
      targeted body weight loss during the moulting period were 20, 24, 25 and 30% of
      body weight at the end of the first egg production cycle. 4. Post-moult egg
      production and egg mass were influenced by all moulting methods. Maximum increase
      in post-moult egg production rate and egg mass occurred with FR and NF
      programmes, respectively, at 30% of body weight loss, compared to non-moulted
      hens. Non-fasting methods reduced mortality rate more effectively than fasting
      methods. 5. Moulting resulted in increases in percentage of grade A and decreases
      in percentage of grade B eggs. Non-fasting methods increased percentage of grade
      A eggs more effectively than fasting methods. Percentage of cracked eggs
      decreased in moulted rather than non-moulted hens and the lowest rate was
      associated with the NA programme. 6. Post-moult egg weight was not significantly
      influenced by moulting methods. However, percentage of body weight reduction
      affected egg weight. The optimum increment in egg weight was achieved by 24% body
      weight reduction. 7. Overall, non-fasting methods resulted in similar egg
      production compared with fasting methods. Considering post-moult mortality and
      USDA egg weight distribution, non-fasting methods, especially NF and NA
      programmes, performed much better than fasting methods, indicating that non
      fasting moulting methods, which are better for animal welfare, are effective
      alternatives to fasting methods.

PMID- 29376739
TI  - The diagnostic accuracy of cross-sectional imaging for detecting acute scaphoid
      fractures in children: a systematic review.
AB  - OBJECTIVE: To determine the diagnostic accuracy of cross-sectional imaging for
      the diagnosis of acute scaphoid fractures in children. METHODS: A systematic
      review of Medline, Embase and Cochrane databases between 1980 and July 2017 was
      independently performed by two observers. Criteria for study inclusion in a meta
      analysis and assessment of the quality of such studies using the QADAS tool, were
      predetermined. RESULTS: No studies were eligible for inclusion in a meta
      analysis. Three studies (of low quality when assessed against the STARD
      guidelines for reporting of studies of diagnostic accuracy) assessed MRI
      (performed between Days 2 and 10 after acute injury) for the diagnosis of
      scaphoid fractures in a total of 119 children (age range 6 to 16 years). Study 1
      (45 children) reported inter-observer reliability of radiographs and MRI of 0.53
      and 0.95 respectively. Study 3 (18 children) reported a negative predictive value
      of MRI (even as early as Day 2), of 100%. No measure of diagnostic accuracy or
      observer reliability was reported in Study 2 (56 children). In all 3 studies, MRI
      identified more scaphoid fractures (and other carpal injuries) than radiographs.
      Study 3 showed that follow-up MRI between Days 38 and 45 added no new information
      compared to initial MRI. CONCLUSION: Based on a systematic review of the
      literature, there is currently no evidence on which to suggest an imaging
      protocol for suspected scaphoid fracture in children. Until such evidence is
      available, existing guidelines (which are based on findings from adult studies)
      should be followed. Advances in knowledge: (1) There is low quality evidence
      regarding the diagnostic accuracy of cross-sectional imaging for suspected
      scaphoid fractures in children and no evidence on which to propose an optimal
      imaging strategy. (2) Until such evidence is available, current guidelines (based
      predominantly on findings in adults and expert opinion) should be followed.

PMID- 29376740
TI  - Evaluation of spinal involvement in children with mucopolysaccharidosis VI: the
      role of MRI.
AB  - OBJECTIVE: To evaluate spinal MRI features of mucopolysaccharidosis (MPS) VI and
      to assess the correlation with clinical findings. METHODS: We retrospectively
      evaluated spinal MRI scans and clinical findings at the time of imaging in 14
      patients (8 male, 6 female) with MPS VI. Craniometric measurements were performed
      and the images were assessed for bony anomalies, spinal stenosis and spinal cord
      compression. The degree of cervical cord compression was scored and correlated
      with neurological examination findings at the time of imaging. Vertebral
      alignment, structural changes in spinal ligaments and intervertebral discs were
      also assessed. RESULTS: All patients had cervical stenosis due to bony stenosis
      and thickened retrodental tissue (median: 6.05 mm, range 3.3-8 mm). Retrodental
      tissue thickness was found to increase with age (p = 0.042). Compressive
      myelopathy was detected at upper cervical level in 11 (79%) and lower thoracic
      level in 2 patients (14%). Significant inverse correlation was found between
      cervical myelopathy scores and neurological strength scores. The most common bony
      changes were hypo/dysplastic odontoid; cervical platyspondyly with anterior
      inferior beaking; thoracic posterior end plate depressions and lumbar posterior
      scalloping. Kyphosis due to retrolisthesis of the beaked lumbar vertebrae and
      acute sacrococcygeal angulations were other remarkable findings. CONCLUSION: MRI
      is an essential component in evaluation of spinal involvement in MPS VI, and
      scanning of the entire spine is recommended to rule out thoracic cord
      compression. Advances in knowledge: This study provides a detailed description of
      spinal MRI findings in MPS VI and underlines the role of MRI in management of
      cord compression.

PMID- 29376741
TI  - Management of elderly patients with glioblastoma-multiforme-a systematic review.
AB  - The management of elderly patients with glioblastoma-multiforme (GBM) remains
      poorly defined with many experts in the past advocating best supportive care, in
      view of limited evidence on efficacy of more aggressive treatment protocols.
      There is randomised evidence (NORDIC and NA-O8 studies) to support the use of
      surgery followed by adjuvant monotherapy with either radiotherapy (RT) using
      hypofractionated regimes (e.g. 36 Gy in 6 fractions OR 40 Gy in 15 fractions) or
      chemotherapy with temozolomide (TMZ) in patients expressing methylation of
      promoter for O6-methylguanine-DNA methyltransferase enzyme. However, the role of
      combined-modality therapy involving the use of combined RT and TMZ protocols has
      remained controversial with data from the EORTC (European Organisation for
      Research and Treatment of Cancer)-NCIC (National Cancer Institute of Canada)
      studies indicating that patients more than 65 years of age may not benefit
      significantly from combining standard RT fractionation using 60 Gy in 30
      fractions with concurrent and adjuvant TMZ. More recently, randomised data has
      emerged on combining hypofractionated RT with concurrent and adjuvant TMZ. We
      provide a comprehensive review of literature with the aim of defining an evidence
      based algorithm for management of elderly glioblastoma-multiforme population.

PMID- 29376744
TI  - Coated blade spray: shifting the paradigm of direct sample introduction to MS.
AB  - Coated blade spray (CBS) is a solid-phase microextraction-based technology that
      can be directly coupled to MS to enable the rapid qualitative and quantitative
      analysis of complex matrices. The goal of this mini review is to concisely
      introduce CBS's operational fundamentals and to consider how it
      correlates/contrasts with existing direct-to-MS technologies suitable for
      bioanalytical applications. In addition, we provide a fair comparison of CBS to
      other existing solid-phase microextraction-to-MS approaches, as well as an
      overview of recent CBS applications/strategies that have been developed to
      analyze diverse compounds present in biofluids.

PMID- 29376743
TI  - National Patterns of Commonly Prescribed Psychotropic Medications to Young
      People.
AB  - OBJECTIVE: To describe national annual prescribing patterns of stimulant,
      antidepressant, and antipsychotic medications to young people. METHODS:
      Prescriptions for three commonly prescribed psychotropic classes (stimulants,
      antidepressants, and antipsychotics) to young people aged 3-24 years were
      analyzed from the IMS LifeLink LRx National Longitudinal Prescription database (n
      = 6,351,482). Denominators were adjusted to generalize estimates to the U.S.
      POPULATION: Comparisons are presented of percentages filling >=1 prescription of
      each medication class during the study year stratified by patient sex, age, and
      prescriber specialty. RESULTS: The total annual percentage of prescriptions
      filled by youth for any of the three medication classes was by age 3-5 years
      (0.8%), 6-12 years (5.4%), 13-18 years (7.7%), and 19-24 years (6.0%). Stimulant
      use was highest for older children (age 11 = 5.7%). Antidepressant use tended to
      increase with age and was highest for young adults (age 24 = 4.8%). Annual
      antipsychotic prescription percentages were lower than antidepressant or
      stimulant percentages for all age groups, with a peak in adolescence (age 16 =
      1.3%). Annual stimulant and antipsychotic percentages for males were higher than
      corresponding percentages for females, but converged for young adults.
      Psychiatrists and child psychiatrists accounted for most of the prescriptions of
      antidepressants (22.2%-53.2%) and antipsychotics (51.7%-70%), but fewer of the
      stimulant prescriptions (30.4%-36.2%). CONCLUSIONS: The age and sex distribution
      of stimulants and antidepressants among young people is broadly consistent with
      known epidemiologic patterns of their established indications for attention
      deficit/hyperactivity disorder, anxiety, and depression. The pattern of
      antipsychotics may reflect the heterogeneity of disorders and conditions treated
      with this medication class.

PMID- 29376747
TI  - Estimating the public economic consequences of introducing varenicline smoking
      cessation therapy in South Korea using a fiscal analytic framework.
AB  - BACKGROUND AND AIMS: Smoking gives rise to many cross-sectorial public costs and
      benefits for government. Costs arise from increased healthcare spending and work
      related social benefits, while smoking itself provides significant revenue for
      government from tobacco taxes. To better understand the public economic impact of
      smoking and smoking cessation therapies, this study developed a government
      perspective framework for assessing smoking-attributable morbidity and mortality
      and associated public costs. This framework includes changes in lifetime tax
      revenue and health costs, as well as changes in tobacco tax revenue, from fewer
      smokers. METHODS: A modified generational accounting framework was developed to
      assess relationships between smoking-attributable morbidity and mortality and
      public economic consequences of smoking, including lifetime tax revenue
      gains/losses, government social transfers, and health spending. Based on the
      current prevalence of smoking in South Korean males, a cohort model was developed
      for smokers, former-smokers, and never-smokers. The model simulated the lifetime
      discounted fiscal transfers for different age cohorts in 5 year age bands, and
      the return on investment (ROI) from smoking cessation therapy. RESULTS: Former
      smokers are estimated to generate higher lifetime earnings and direct tax
      revenues and lower lifetime healthcare costs due to the reduction of smoking
      attributable mortality and morbidity compared to smokers, even after accounting
      for reduced tobacco taxes paid. Based on the costs of public investments in
      varenicline, this study estimated a ROI from 1.4-1.7, depending on treatment age,
      with higher ROI in younger cohorts, with an average ROI of 1.6 for those aged
      less than 65. CONCLUSIONS: This analysis suggests that reductions in smoking can
      generate positive public economic benefits for government, even after accounting
      for lost tobacco tax revenues. The results described here are likely applicable
      to countries having similar underlying smoking prevalence, comparable taxation
      rates, and social benefit protection provided to individuals with smoking-related
      conditions.

PMID- 29376746
TI  - Carbon stable isotope composition of modern and archaeological Cornelian cherry
      fruit stones: a pilot study.
AB  - The carbon stable isotope content of Cornelian cherry stones collected from wild
      tree stands in Serbia, SE Europe, was measured using elemental analyser-isotope
      ratio mass spectrometry, with the aim of recording natural carbon isotope
      composition of the fruit stones and its possible variation. The results show a
      significant variation in the carbon isotope values; we identified several
      environmental factors that, along with a number of other possible determinants,
      likely contributed to this variation. The obtained data are compared with the
      measurement of carbon isotope content of an archaeological specimen of Cornelian
      cherry stone discovered at the Neolithic site of Vinca (ca. 5600-4500 BC) in
      Serbia. Notwithstanding the limitedness of the data and the complexity
      surrounding carbon fractionation and the isotopic variation, it is suggested that
      the differences/similarities in carbon isotope ratios between modern and
      archaeological Cornelian cherry stones, when measured for much larger
      assemblages, could potentially offer a glimpse into growing conditions of
      Cornelian cherry trees in the past.

PMID- 29376745
TI  - Prediction of detectability of the mandibular canal by quantitative image quality
      evaluation using cone beam CT.
AB  - OBJECTIVES: To compare the results of a new quantitative image quality evaluation
      method that requires no observers with the results of receiver operating
      characteristic (ROC) analysis in detecting the mandibular canal (MC) in cone beam
      CT (CBCT) images. METHODS: A Teflon (polytetrafluoroethylene) plate phantom with
      holes of different depths was scanned with two CBCT systems. One CBCT system was
      equipped with an image intensifier (Experiment 1), and the other was equipped
      with a flat panel detector (Experiment 2). Holes that were above the threshold
      gray value (DeltaG), calculated using just-noticeable difference (JND), were
      extracted. The number of extracted holes was used as the index of the image
      quality, and was compared with the Az values calculated by ROC analysis to detect
      the MC. RESULTS: The number of extracted holes reflected the influence of
      different scanning conditions, and showed a strong correlation with the Az values
      calculated by ROC analysis. Indices of the number of extracted holes
      corresponding to high Az values for detecting the MC were obtained in both
      experiments. CONCLUSIONS: Our image quality evaluation method applying JND to
      images of a standardized phantom is a quantitative method that could be useful
      for evaluating the detectability of the MC in CBCT images.

PMID- 29376748
TI  - Claimed effects, outcome variables and methods of measurement for health claims
      on foods related to the gastrointestinal tract proposed under regulation (EC)
      1924/2006.
AB  - Most of the requests of authorisation to the use of health claims pursuant to
      Regulation EC 1924/2006 related to the gastrointestinal (GI) tract have received
      a negative opinion by the European Food Safety Authority (EFSA), mainly because
      of an insufficient substantiation of the claimed effect (CE). The present
      manuscript refers to the collection, collation and critical analysis of outcome
      variables (OVs) and methods of measurement (MMs) related to the GI tract
      compliant with Regulation 1924/2006. The critical evaluation of OVs and MMs was
      based on the literature review, with the final aim of defining their
      appropriateness in the context of a specific CE. The results obtained are
      relevant for the choice of the best OVs and MMs to be used in randomised
      controlled trials aimed to substantiate the claims on the GI tract. Moreover, the
      results can be used by EFSA for updating the guidance for the scientific
      requirements of such health claims.

PMID- 29376750
TI  - Heterozygous familial hypercholesterolemia and HIV infection: The appropriate
      therapeutic flow chart is still to be written?

PMID- 29376751
TI  - Shared preventive strategies between cardiovascular diseases and
      neurodegenerative diseases.

PMID- 29376749
TI  - Beneficial effects of inhaled nitric oxide with intravenous steroid in an
      ischemia-reperfusion model involving aortic clamping.
AB  - This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined
      with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and
      kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia
      reperfusion injury animal model. The primary endpoint was the evaluation of
      circulatory, respiratory, and renal function over time. We also investigated the
      profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as
      well as renal mRNA TLR4 activation determined by quantitative real-time
      polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa
      anesthesia/sedation were randomized and subjected to abdominal laparotomy and
      alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham
      surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg *3) started 30
      min before SRACC and continued 2 h after SRACC release, followed with decreased
      iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3
      (n = 3)-sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and
      20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in
      ischemic kidneys, but significant changes were recorded only in the control group
      ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression
      to pre-ischemic conditions, and the difference observed in mRNA expression was
      significant between control and treatment group after 3 h ( P = 0.042). Moreover,
      animals subjected to treatment with iNO and hydrocortisone displayed an
      attenuated systemic inflammatory response and lowered pulmonary vascular
      resistance plus increased oxygen delivery. The results indicated that iNO therapy
      combined with IV corticosteroids improved central and systemic hemodynamics,
      oxygen delivery, and diminished the systemic inflammatory response and renal mRNA
      TLR4 expression.

PMID- 29376752
TI  - Association between serum calcium, serum phosphate and aortic stenosis with
      implications for prevention.
AB  - Background Aortic stenosis is the most common cause of valvular heart disease
      with no means of prevention. Lowering serum levels of calcium or phosphate are
      potential preventive strategies but observational studies on the associations
      with aortic stenosis are inconsistent. Design and methods A case-control study
      was conducted in 132 individuals undergoing echocardiography (63 with aortic
      stenosis and 69 without) and the results combined with three other comparable
      studies (914 individuals overall) to provide a summary odds ratio of aortic
      stenosis for a 0.1 mmol/L increase (approximately one standard deviation) in
      calcium and phosphate respectively. The relationship between calcium and
      phosphate and the severity of aortic stenosis, according to peak trans-aortic
      velocity, was also examined in the case-control study using linear regression.
      Results Both calcium and phosphate were positively associated with aortic
      stenosis. The summary odds ratio for a 0.1 mmol/L increase in calcium was 1.79
      (95% confidence interval 1.07-2.99), p = 0.027 and for phosphate it was 1.47
      (1.08-2.01), p = 0.015. Peak trans-aortic velocity increased with phosphate
      levels, 9% (4%-14%) per 0.1 mmol/L, p = 0.001, but not with calcium, p = 0.089.
      Conclusions If the associations are causal and reversible, these results indicate
      that a small reduction in calcium or phosphate levels, within the physiological
      rage, would translate into a clinically significant reduction in the risk of
      aortic stenosis. Randomised trials of calcium and phosphate lowering therapies in
      aortic stenosis are needed.

PMID- 29376753
TI  - Cardiovascular diseases in patients receiving small molecules with anti-vascular
      endothelial growth factor activity: A meta-analysis of approximately 29,000
      cancer patients.
AB  - Background Targeted therapy with tyrosine kinase inhibitors with anti-vascular
      endothelial growth factor activity improves survival of cancer patients.
      Cardiovascular complications are critical and it is unknown whether these require
      specific treatment strategies. We aimed to clarify the associated risk of
      cardiovascular adverse events in patients treated with tyrosine kinase
      inhibitors. Design The design of this study was a meta-analysis of randomised
      controlled trials. Methods We searched PubMed, Cochrane, EMBASE and Web of
      Science databases for randomised controlled trials published until January 2017
      that assessed patients with different types of cancer treated with or without
      tyrosine kinase inhibitors in addition to standard chemotherapy. Results A total
      of 29,252 patients from 71 randomised controlled trials were included. Tyrosine
      kinase inhibitor treatment was associated with a higher cardiac ischaemia
      relative risk (relative risk = 1.69; 95% confidence interval: 1.12-2.57; p =
      0.01), with the highest risks observed for sorafenib and patients with renal
      cancer. Risk of thrombocytopaenia (relative risk = 2.2; 95% confidence interval:
      1.73-2.79; p < 0.001) was highest for regorafenib and patients with breast
      cancer. Left ventricular systolic dysfunction was increased after tyrosine kinase
      inhibitor therapy (relative risk = 2.53; 95% confidence interval:1.79 - 3.57; p <
      0.001), with the highest risks reported for sunitinib and hepatocellular cancer.
      QT corrected interval prolongation (relative risk = 6.25; 95% confidence
      interval: 3.44-11.38; p < 0.001) and arterial hypertension (relative risk = 3.78;
      95% confidence interval: 3.15-4.54; p < 0.001) were reported. The relative risks
      of arterial adverse events, cerebral ischaemia, venous adverse events and
      pulmonary embolism were similar across groups. Conclusion Tyrosine kinase
      inhibitors increase the risk of severe cardiovascular and particularly thrombotic
      adverse events. Specific treatment regimens when prescribing tyrosine kinase
      inhibitor therapies appear desirable.

PMID- 29376754
TI  - Relation between aortic knob width and subclinical left ventricular dysfunction
      in hypertensive patients.
AB  - BACKGROUND: The assessment of left ventricular (LV) structure and function is
      important in the evaluation of hypertensive heart disease, as it provides
      information on the cardiovascular morbidity and mortality. Aortic knob width
      (AKW) is a measurement of radiographic structure formed by the foreshortened
      aortic arch and a portion of the descending aorta. The main aim of this study was
      to investigate the relation between AKW on the routine chest radiography and
      subclinical LV dysfunction in hypertensive patients. PATIENTS AND METHODS: A
      total of 144 patients with hypertension admitted to the cardiology outpatients
      clinic were enrolled consecutively. The patients were divided into two groups
      according to tissue Doppler-derived myocardial performance index (MPI):
      subclinical LV dysfunction group (abnormal MPI >= 0.5, n = 85) and absence of
      subclinical LV dysfunction group (normal MPI< 0.5, n = 59). RESULTS: Patients
      with subclinical LV dysfunction were older (60 +/- 8 vs. 54 +/- 8, p = 0.001).
      Left ventricular mass index (LVMI) (96 +/- 27 vs. 74 +/- 24, p < 0.001) and
      prevalence of LV hypertrophy (28 vs. 8%, p = 0.011) were significantly different
      between two groups. Patients with subclinical LV dysfunction had higher AKW (42
      +/- 6 vs. 34 +/- 5, p < 0.001) compared with patients without subclinical LV
      dysfunction. There was a significant correlation between MPI and AKW (r = 0.7, p
      < 0.001). Multiple logistic regression analysis showed that AKW (beta = 0.617, p
      = 0.001) and posterior wall thickness (PWth) (beta = 1.189, p = 0.021) were
      independently associated with subclinical LV dysfunction. Analysis using the
      Receiver Operating Characteristic (ROC) curve has demonstrated that aortic knob
      of 37 mm constitutes the cutoff value for the presence of subclinical LV
      dysfunction with 85.9% sensitivity and 86.4% specificity (The Area under the
      Curve +/- Standard Error (AUC+/-SE) = 0.916 +/- 0.024, p < 0.001). CONCLUSION:
      AKW may provide important predictive information on subclinical LV dysfunction in
      patients with hypertension.

PMID- 29376756
TI  - Foreword - Increase in clinical trials for probiotics and prebiotics.
AB  - After a steady increase over recent years, last year we experienced our first
      drop in Impact Factor (IF): from 3.301 to 2.923. Although last year I concluded
      that I was pretty awful at predicting the future (Venema, 2017; and I still
      haven't found a probiotic to improve that ...), this result was not entirely
      unexpected. As a young journal (we have yet to celebrate our 10th anniversary),
      the IF will inevitably fluctuate a little. I keep track of the IF development
      over the course of the year and we are well on our way to achieving an IF of
      above 2 again (with still another 6 months to go until the end of June, when the
      new impact factors will be provided by Clarivate Analytics), which isn't bad at
      all for a young journal.

PMID- 29376757
TI  - Bone-targeting dendrimer for the delivery of methotrexate and treatment of bone
      metastasis.
AB  - We developed a bone-targeting dendrimer for the delivery of anti-tumour agents
      and effective treatment of bone metastasis, in which alendronate (ALN), a bone
      targeting moiety, is covalently bonded to a polyethylene glycol (PEG)-conjugated
      polyamidoamine (PAMAM) dendrimer (PEG-PAMAM-ALN). Approximately 7.0 and 21.9% of
      the administered doses of [111In]PAMAM and PEG-PAMAM-ALN accumulated in the bones
      within 180 min after intravenous injection in mice, respectively. [3H]-labelled
      methotrexate (MTX) rapidly disappeared from the blood, and bone distribution was
      found to be only 1.1% of the administered dose at 180 min. In contrast, 21.5% of
      the administered dose of [3H]MTX-loaded PEG-PAMAM-ALN accumulated in the bones at
      180 min after intravenous injection in mice, which was approximately 20-fold
      higher than that of [3H]MTX. In a bone metastatic tumour mouse model, in which
      B16-BL6/Luc cells were injected into the left ventricle of female C57BL/6 mice,
      the growth of metastatic tumour in the bones was significantly inhibited by
      intravenous injection of MTX-loaded PEG-PAMAM-ALN. These findings indicate that
      PEG-PAMAM-ALN is a promising bone-targeting carrier for the delivery of anti
      tumour agents and treatment of bone metastasis.

PMID- 29376758
TI  - Responsible Life Science Research: The Pakistani Leadership Model.

PMID- 29376759
TI  - Oestrogen receptor-mediated liposomal drug delivery for treating melanoma.
AB  - Function of steroid hormone oestrogen that transactivates oestrogen receptor (ER)
      is expressed in multiple organs. Except for malignancies of gynaecological
      organs, ER remains largely unutilised as a target to treat cancers of ER
      expressing brain, prostate, skin etc. We have previously developed oestrogen
      targeting cationic lipid molecule (ES-C10), which showed targeted killing of ER +
      breast and skin cancer cells. In this study, we explored the targeting ability of
      ES-C10 as a ligand as well as its additive killing effect (if any), when
      incorporated in two different liposomes (DCME and DCDE), carrying two anticancer
      molecules MCIS3 and DocetaxelTM, respectively. DCME and DCDE exhibited higher
      cytotoxicity in ER + cancer cells than in ER - cancer or in non-cancer cells.
      Both liposomes induced ER-mediated cytotoxicity and caspase 3-induced apoptosis
      in ER + melanoma cells. Further, decreased levels of pAkt, and increased levels
      of PTEN and p53 were also observed. Both the targeted liposomes were least
      haemolytic. These selectively delivered drug-cargoes to tumour mass over other
      vital organs and induced better anti-tumour effect, which led to increased
      survivability than their respective controls. In conclusion, we demonstrated the
      development of two independent liposomal drug-delivery systems associated with an
      anticancer, oestrogen-structure based ligand for efficient, ER-mediated anti
      melanoma effect.

PMID- 29376760
TI  - Comparison of costs and outcomes of dapagliflozin with other glucose-lowering
      therapy classes added to metformin using a short-term cost-effectiveness model in
      the US setting.
AB  - OBJECTIVE: To compare 1-year costs and benefits of dapagliflozin (DAPA), a sodium
      glucose cotransporter-2 (SGLT-2) inhibitor, with those of other treatments for
      type 2 diabetes (T2D), such as glucagon-like peptide-1 receptor agonists (GLP
      1RAs), sulfonylureas (SUs), thiazolidinediones (TZDs), and dipeptidyl peptidase-4
      inhibitors (DPP-4i), all combined with metformin. METHODS: A short-term decision
      analytic model with a 1-year time horizon was developed from a payer's
      perspective in the United States setting. Costs and benefits associated with four
      clinical end-points (glycated hemoglobin [A1C], body weight, systolic blood
      pressure [SBP], and risk of hypoglycemia) were evaluated in the analysis. The
      impact of DAPA and other glucose-lowering therapy classes on these clinical end
      points was estimated from a network meta-analysis (NMA). Data for costs and
      quality-adjusted life-years (QALYs) associated with a per-unit change in these
      clinical end-points were taken from published literature. Drug prices were taken
      from an annual wholesale price list. All costs were inflation-adjusted to
      December 2016 costs using the medical care component of the consumer price index.
      Total costs (both medical and drug costs), total QALYs, and incremental cost
      effectiveness ratios (ICERs) were estimated. Sensitivity analyses (SA) were
      performed to explore uncertainty in the inputs. To assess face validity, results
      from the short-term model were compared with long-term models published for these
      drugs. RESULTS: The total annual medical cost for DAPA was less than that for GLP
      1RA ($186 less), DPP-4i ($1,142 less), SU ($2,474 less), and TZD ($1,640 less).
      Treatment with DAPA resulted in an average QALY gain of 0.0107, 0.0587, 0.1137,
      and 0.0715 per treated patient when compared with GLP-1RA, DPP-4i, SU, and TZD,
      respectively. ICERs for DAPA vs SU and TZD were $19,005 and $25,835,
      respectively. DAPA was a cost-saving option when compared with GLP-1RAs and DPP
      4is. Among all four clinical end-points, change in weight had the greatest impact
      on total annual costs and ICERS. Sensitivity analysis showed that results were
      robust, and results from the short-term model were found to be similar to those
      of published long-term models. CONCLUSION: This analysis showed that DAPA was
      cost-saving compared with GLP-1RA and DPP-4i, and cost-effective compared with SU
      and TZD in the US setting over 1 year. Furthermore, the results suggest that,
      among the four composite clinical end-points, change in weight and SBP had an
      impact on cost-effectiveness results.

PMID- 29376761
TI  - Meaningful relief with flurbiprofen 8.75 mg spray in patients with sore throat
      due to upper respiratory tract infection.
AB  - AIM: Evaluate the efficacy of flurbiprofen 8.75 mg spray for sore throat relief.
      PATIENTS & METHODS: Randomized, double-blind study in adults with sore throat due
      to upper respiratory tract infection who took flurbiprofen (n = 249) or placebo
      spray (n = 256). Pain relief was assessed using the Sore Throat Relief Rating
      Scale. RESULTS: Flurbiprofen spray provided significantly greater relief versus
      placebo from 20 min to 6 h (p < 0.0001; maximum difference: 75 min). Sore throat
      severity was reduced >=-2.2 on the Sore Throat Scale from 75 min to 6 h,
      indicating meaningful relief. Significantly more patients taking flurbiprofen
      spray reported >=30 min of 'at least moderate' relief versus placebo over 6 h (p
      < 0.0001). Most adverse events were mild. CONCLUSION: Flurbiprofen spray provides
      rapid, long-lasting and clinically meaningful relief from sore throat (ANZCTR:
      ACTRN12612000457842).

PMID- 29376762
TI  - Cluster analysis for repeated data with dropout: Sensitivity analysis using a
      distal event.
AB  - Degeneration of the aortic wall becomes life-threatening when the risk of rupture
      increases. Cluster analysis on repeated measures of the diameter of the artery
      revealed two subgroups of patients included in a surveillance program. These
      results were obtained under the assumption of missingness at random. In this
      article, we study the vulnerability of the cluster analysis results - the
      estimated trajectories and the posterior membership probabilities - by applying
      different missing-data models for non-ignorable dropout, as proposed by Muthen et
      al. (2011) to the growth of the diameter of the artery.

PMID- 29376763
TI  - Enhancing individual and collaborative eyewitness memory with category clustering
      recall.
AB  - Most crimes have multiple eyewitnesses. The police typically interview co
      witnesses separately. In time-sensitive investigations, this could slow down
      evidence accumulation. Having co-witnesses collaboratively recall a crime could
      potentially expedite evidence accumulation. However, past research shows that
      collaborative group members often have conflicting retrieval strategies that
      disrupt each other, degrading overall recall. This cost could potentially be
      overcome by aligning group members' retrieval strategies with category clustering
      recall (CCR), which is a retrieval strategy where information is recalled from a
      series of forensically relevant categories (e.g., recalling the protagonists'
      appearance, then actions). This study examined the costs and benefits of
      collaborative eyewitness memory by having collaborative pairs of strangers,
      nominal pairs (i.e., two individuals whose recall is pooled) and lone individuals
      watch a crime and recall it using free recall or CCR. The collaborative pairs
      recalled the crime faster than the nominal pairs. They also recalled more correct
      information than individuals but less than nominal pairs, irrespective of the
      retrieval method. There is therefore a speed-recall completeness trade-off when
      collaborative groups recall crimes. Importantly, all participants recalled more
      correct information when using CCR. This provides initial evidence suggesting
      that CCR is superior to free recall. Further research examining CCR's benefits is
      recommended.

PMID- 29376764
TI  - Metallated porphyrin-doped conjugated polymer nanoparticles for efficient
      photodynamic therapy of brain and colorectal tumor cells.
AB  - AIM: Assess biocompatibility, uptake and photodynamic therapy (PDT) mechanism of
      metallated porphyrin doped conjugated polymer nanoparticles (CPNs) in human brain
      and colorectal tumor cells and macrophages. MATERIALS & METHODS: CPNs were
      developed employing 9,9-dioctylfluorene-alt-benzothiadiazole, an amphiphilic
      polymer (PS-PEG-COOH),  and platinum octaethylporphyrin. T98G, SW480 and RAW
      264.7 cell lines were exposed to CPNs to assess uptake and intracellular
      localization. Additionally, a PDT protocol using CPNs was employed for the in
      vitro killing of cancer and macrophage cell lines. RESULTS & CONCLUSION: CPNs
      were well incorporated into glioblastoma and macrophage cells with localization
      in lysosomes. SW480 cells were less efficient incorporating CPNs with
      localization in the plasma membrane. In all cell lines PDT treatment was
      efficient inducing oxidative stress that triggered apoptosis.

PMID- 29376765
TI  - Phytosomal bilayer-enveloped casein micelles for codelivery of monascus yellow
      pigments and resveratrol to breast cancer.
AB  - AIM: Multireservoir nanocarriers were fabricated for delivering antineoplastic
      drug cocktail from herbal and fungal origin. Monascus yellow pigments (MYPs),
      monascin and ankaflavin, were isolated from red-mold rice, and incorporated
      within casein micelles (CAS MCs) along with the herbal drug, resveratrol (RSV).
      Both drugs (MYPs and RSV) were simultaneously incorporated into the hydrophobic
      core of CAS MCs. Alternatively, MYPs-loaded CAS MCs were enveloped within RSV
      phytosomal bilayer elaborating multireservoir nanocarriers. RESULTS: Cytotoxicity
      studies confirmed the superiority of multireservoir nanocarriers against MCF-7
      breast cancer cells. The in vivo antitumor efficacy was revealed by reduction of
      the tumor volume and growth biomarkers. CONCLUSION: Multireservoir CAS
      nanocarriers for codelivery of both MYPs and RSV may be promising alternative to
      traditional breast cancer therapy.

PMID- 29376766
TI  - Recollection improves with age: children's and adults' accounts of their
      childhood experiences.
AB  - Since the time of Freud, psychologists have drawn conclusions about children's
      memory on the basis of retrospective research with adults. Here, we turn the
      tables by examining what prospective studies with children and adolescents can
      tell us about the retrospective memory accounts provided by adults. Adults were
      interviewed about recent events and events from different points during their
      childhood (Age 5, Age 10) and early adolescence (Age 13). Children (5- and 8- to
      9-year-olds) and young adolescents (12- to 13-year-olds) were interviewed about
      recent events. When matched for age at the time of encoding, adults recalled more
      about the target events than did 5-year-olds, even though the retention interval
      for adults was substantially longer. We conclude that retrospective studies with
      adults may lead researchers to overestimate the content of the early childhood
      memories that survive. We discuss the theoretical implications of these findings
      for an understanding of memory development and the practical implications for the
      interpretation of adults' retrospective accounts in the courtroom.

PMID- 29376767
TI  - Re-examination of "release-from-PI" phenomena: recall accuracy does not recover
      after a semantic switch.
AB  - Recall accuracy decreases over successive memory trials using similar memoranda.
      This effect reflects proactive interference (PI) - the tendency for previously
      studied information to reduce recall of new information. However, recall improves
      if memoranda for a subsequent trial are semantically dissimilar from the previous
      trials. This improvement is thought to reflect a release from PI. We tested
      whether PI is reduced or released from the semantic category for which it had
      been induced by employing paradigms which featured inducement, semantic switch,
      and then return-to-original category epochs. Two experiments confirmed that PI
      was not released after various semantic switch trials (effects from d = -0.93 to 
      1.6). Combined analyses from both studies demonstrated that the number of
      intervening new category trials did not reduce or release PI. In fact, in all
      conditions recall accuracy decreased, demonstrating that PI is maintained and can
      increase after the new category trials. The release-from-PI account cannot
      accommodate these broader dynamics of PI. This account is also incongruent with
      evidence and theory from cognitive psychology, linguistics, and neuroscience. We
      propose a reintroduction-of-PI account which explains these broader PI dynamics
      and is consistent with the wider psychological and neurosciences.

PMID- 29376768
TI  - An efficient and practical synthesis of formylglycinamide ribonucleotide (FGAR).
AB  - An efficient five-step synthetic route for multigram-scale preparation of
      formylglycinamide ribonucleotide (FGAR) from peracetylated beta-d-ribofuranosyl
      azide has been developed.

PMID- 29376769
TI  - Tricyclic nitrogen base 1,N6-ethenoadenine and its ribosides as substrates for
      purine-nucleoside phosphorylases: Spectroscopic and kinetic studies.
AB  - The title compound is an excellent substrate for E. coli PNP, as well as for its
      D204N mutant. The main product of the synthetic reaction is N9-riboside, but some
      amount of N7-riboside is also present. Surprisingly, 1,N6-ethenoadenine is also
      ribosylated by both wild-type and mutated (N243D) forms of calf PNP, which
      catalyze the synthesis of a different riboside, tentatively identified as N6-beta
      D-ribosyl-1,N6-ethenoadenine. All ribosides are susceptible to phosphorolysis by
      the E. coli PNP (wild type). All the ribosides are fluorescent and can be
      utilized as analytical probes.

PMID- 29376770
TI  - Sacral examination in spinal cord injury: Is it really needed?
AB  - OBJECTIVE: To determine if a self-report measure of S4-5 motor and sensory
      function in patients with chronic SCI accurately predicts sacral examination
      results. DESIGN: Prospective, single-blinded self-report survey compared with
      sacral exam. SETTING: Outpatient SCI clinic. PARTICIPANTS: 116 patients aged 18+
      with chronic SCI > 6 months who have undergone sacral exam. INTERVENTIONS: The
      survey included demographic/clinical and sacral function information such as
      light tough (LT), pinprick sensation (PP), deep anal pressure (DAP) and voluntary
      anal contraction (VAC). Survey results and sacral exam were compared and
      stratified by the patient's American Spinal Cord Injury Association Impairment
      Scale (AIS) category. OUTCOME MEASURES: Sacral self-report survey, AIS
      examination. RESULTS: Mean age was 41.3 +/- 14.4 years with majority male (69%)
      and Caucasian (71.6%). Overall, Positive Predictive Value (PPV) ranged between
      48% (VAC) to 73% (DAP) and Negative Predictive Value (NPV) between 92% (VAC) to
      100% (LT). AIS-A had NPV of 100% across all categories, and AIS-D had PPV of 100%
      across all categories. CONCLUSION: Patient report of sacral sparing can predict
      negative sensation in patients with AIS-A and predict positive sensation in
      persons with AIS-D. Overall, the self-report of sacral sparing of motor and
      sensory function is not predictive enough to rely on for accurate classification.

PMID- 29376773
TI  - Can spatialisation be extended to episodic memory and open sets?
AB  - The SPoARC effect (Spatial Positional Associated Response Codes) has only been
      observed in working memory (WM) using closed sets. It is interpreted as showing
      that individuals spatialise to-be-remembered items in a left-to-right fashion,
      using spatialisation as context. Given that context is crucial for episodic
      memory (EM), we tested if this effect could be observed in EM by using 15-word
      lists taken from an open set. After each list, 30 probes were sequentially
      displayed to test recognition. The left/right-hand key assignment for yes/no
      answers was varied. No SPoARC effect was observed. However, as all previous
      SPoARC experiments had used short lists and closed sets, it was not possible to
      know if this absence of SPoARC was due to the open set feature or the length of
      the lists. A second experiment was thus run using open sets and short 5-word
      lists, which do not necessitate EM to be remembered. A SPoARC effect was observed
      indicating that Experiment 1 result was due to the involvement of supra-span
      lists and that SPoARC effects do not extend to EM with open sets. Experiment 2
      also enabled us to generalise the SPoARC effect to open sets in WM for the first
      time.

PMID- 29376774
TI  - Comparison of affective responses during and after low volume high-intensity
      interval exercise, continuous moderate- and continuous high-intensity exercise in
      active, untrained, healthy males.
AB  - This study compared affective responses to low volume high-intensity interval
      exercise (HIIE), moderate-intensity continuous exercise (MICE) and high-intensity
      continuous exercise (HICE). Twelve untrained males ([Formula: see text] 48.2 +/-
      6.7 ml.kg-1.min-1) completed MICE (30 min cycle at 85% of ventilatory threshold
      (VT)), HICE (cycle at 105% of VT matched with MICE for total work), and HIIE (10
      x 6 s cycle sprints with 60 s recovery). Affective valence and perceived
      activation were measured before exercise, post warm-up, every 20% of exercise
      time, and 1, 5, 10, and 15 min post-exercise. Affective valence during exercise
      declined by 1.75 +/- 2.42, 1.17 +/- 1.99, and 0.42 +/- 1.38 units in HICE, HIIE,
      and MICE, respectively, but was not statistically influenced by trial (P = 0.35),
      time (P = 0.06), or interaction effect (P = 0.08). Affective valence during HICE
      and HIIE was consistently less positive than MICE. Affective valence post
      exercise was not statistically influenced by trial (P = 0.10) and at 5 min post
      exercise exceeded end-exercise values (P = 0.048). Circumplex profiles showed no
      negative affect in any trial. Affective responses to low volume HIIE are similar
      to HICE but remain positive and rebound rapidly, suggesting it may be a potential
      alternative exercise prescription.

PMID- 29376775
TI  - Influence of ionic crosslinkers (Ca2+/Ba2+/Zn2+) on the mechanical and biological
      properties of 3D Bioplotted Hydrogel Scaffolds.
AB  - Three dimensional (3D) bioplotting requires appropriate crosslinkers to crosslink
      the hydrogel precursor while simultaneously maintaining the viability of embedded
      cells. However, the evaluation and comparison of various types of crosslinkers in
      bioplotting remains underexplored to date. This paper presents our study of the
      influence of three ionic crosslinkers-calcium chloride (CaCl2), barium chloride
      (BaCl2), and zinc chloride (ZnCl2)-on the mechanical and biological properties of
      3D bioplotted alginate scaffolds. The scaffold mechanical properties
      characterized included the elastic modulus, swelling, and degradation while the
      biological properties considered included Schwann cell viability and surface
      morphology. The mechanical and biological properties of the bioplotted scaffolds
      were both dependent on the crosslinkers used for fabrication; specifically,
      crosslinking ions resulted in the elastic modulus of the hydrogels decreasing in
      the order BaCl2>CaCl2>ZnCl2 over 42 days while Schwann cell viability decreased
      in the order CaCl2>BaCl2>ZnCl2 over 7 days. Taken together, these results offer
      insights that are effective in terms of manipulating the 3D bioplotting process
      so as to tune and optimize the mechanical and biological performance of the
      plotted scaffolds for tissue engineering applications.

PMID- 29376777
TI  - The mysterious thymus gland and its surgery.

PMID- 29376776
TI  - A natively paired antibody library yields drug leads with higher sensitivity and
      specificity than a randomly paired antibody library.
AB  - Deep sequencing and single-chain variable fragment (scFv) yeast display methods
      are becoming more popular for discovery of therapeutic antibody candidates in
      mouse B cell repertoires. In this study, we compare a deep sequencing and scFv
      display method that retains native heavy and light chain pairing with a related
      method that randomly pairs heavy and light chain. We performed the studies in a
      humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen. We
      identified 44 high-affinity binder scFv with the native pairing method and 100
      high-affinity binder scFv with the random pairing method. 30% of the natively
      paired scFv binders were also discovered with the randomly paired method, and 13%
      of the randomly paired binders were also discovered with the natively paired
      method. Additionally, 33% of the scFv binders discovered only in the randomly
      paired library were initially present in the natively paired pre-sort library.
      Thus, a significant proportion of "randomly paired" scFv were actually natively
      paired. We synthesized and produced 46 of the candidates as full-length
      antibodies and subjected them to a panel of binding assays to characterize their
      therapeutic potential. 87% of the antibodies were verified as binding IL-21R by
      at least one assay. We found that antibodies with native light chains were more
      likely to bind IL-21R than antibodies with non-native light chains, suggesting a
      higher false positive rate for antibodies from the randomly paired library.
      Additionally, the randomly paired method failed to identify nearly half of the
      true natively paired binders, suggesting a higher false negative rate. We
      conclude that natively paired libraries have critical advantages in sensitivity
      and specificity for antibody discovery programs.

PMID- 29376778
TI  - Perioperative management of implantable cardioverter defibrillators.

PMID- 29376780
TI  - The theatre 'cockpit' - lessons from aviation.

PMID- 29376781
TI  - Auld Lang Syne.

PMID- 29376783
TI  - An evaluation of a flipped approach to risk training in the operating theatre.

PMID- 29376782
TI  - A rare reaction to synthetic mono-filament sutures: a report of two cases.
AB  - Due to their clinical advantages, synthetic mono-filament sutures are dominantly
      used for postoperative wound closures. We present two patients who suffered rare
      skin reactions to either poliglecaprone 25 or glyconate sutures, following breast
      cancer lumpectomy. This report aims to make perioperative practitioners and
      clinicians aware of reactions to sutures and possible management options.

PMID- 29376785
TI  - Which pen? A comparative study of surgical site markers.
AB  - A preoperative requirement is the correct and clear marking of a specific
      surgical site. We aimed to compare the ability of marker pens to withstand
      surgical preparation. Five volunteers with different Fitzpatrick skin types were
      marked with ten pens. Marked skin sites were prepared with chlorhexidine followed
      by chlorhexidine, betadine followed by chlorhexidine, and betadine followed by
      betadine. Each site was photographed in theatre. Two volunteers ranked the top
      three most visible marker pens from each photograph. The results showed that
      Sharpie(r) W10 black, Dual Tip (Purple Surgical), and Easimark modern regular tip
      (Leonhard Lang) were the best performers across all skin types. Red pen should be
      avoided with betadine skin preparation. The study concludes that the above named
      three markers are the best at withstanding surgical skin preparation. Different
      skin types require different colour ink for maximal clarity in marking. Biro and
      drywipe markers should never be used for surgical marking.

PMID- 29376786
TI  - The effect of multimedia-based nursing visit on preoperative anxiety and vital
      signs in patients undergoing lumbar disc herniation surgery: A randomised
      clinical trial.
AB  - This study was a randomised clinical trial on 60 candidates undergoing lumbar
      disc herniation surgery. Anxiety rate and vital signs were measured before and
      after the intervention. There was a statistically significant difference between
      the two groups in terms of the preoperative anxiety, systolic and diastolic blood
      pressure, pulse and respiratory rate (P = 0.0001). Neurosurgery perioperative
      nurses can make use of multimedia in preoperative nursing visit based on the
      needs of patients.

PMID- 29376819
TI  - Associations between provider and hospital volumes and postoperative mortality
      following total hip arthroplasty in New Brunswick: results from a provincial
      level cohort study.
AB  - BACKGROUND: Several international studies have reported negative associations
      between hospital and/or provider volume and risk of postoperative death following
      total hip arthroplasty (THA). The only Canadian studies to report on this have
      been based in Ontario and have found no such association. We describe
      associations between postoperative deaths following THA and provider caseload
      volume, also adjusted for hospital volume, in a population-based cohort in New
      Brunswick. METHODS: Our analyses are based on hospital discharge abstract data
      linked to vital statistics and to patient registry data. We considered all first
      known admissions for THA in New Brunswick between Jan. 1, 2007, and Dec. 31,
      2013. Provider volume was defined as total THAs performed over the preceding 2
      years. We fit logistic regression models to identify odds of dying within 30 and
      90 days according to provider caseload volume adjusted for selected personal and
      contextual characteristics. RESULTS: About 7095 patients were admitted for THA in
      New Brunswick over the 7-year study period and 170 died within 30 days. We found
      no associations with provider volume and postoperative mortality in any of our
      models. Adjustment for contextual characteristics or hospital volume had no
      effects on this association. CONCLUSION: Our results suggest that patients
      admitted for hip replacements in New Brunswick can expect to have similar risk of
      death regardless of whether they are admitted to see a provider with high or low
      THA volumes and of whether they are admitted to the province's larger or smaller
      hospitals.

PMID- 29376820
TI  - Kidney paired donation and the unique challenges of kidney shipment in Canada.
AB  - SUMMARY: Kidney paired donation (KPD) programs are an effort to bridge the
      disparity between kidney supply and demand. These programs combine several
      incompatible donor-recipient pairs in a national paired exchange database,
      thereby increasing the number of compatible matches. But KPD programs face unique
      challenges, particularly the large distances that often separate donors and
      recipients. Here we discuss key factors to consider when transitioning from a
      donor travelling model to a kidney shipment model in the Canadian context.

PMID- 29376821
TI  - Surgical intervention in pediatric trauma at a level 1 trauma hospital: a
      retrospective cohort study and report of cost data.
AB  - BACKGROUND: Given that the management of severely injured children requires
      coordinated care provided by multiple pediatric surgical subspecialties, we
      sought to describe the frequency and associated costs of surgical intervention
      among pediatric trauma patients admitted to a level 1 trauma centre in
      southwestern Ontario. METHODS: All pediatric (age < 18 yr) trauma patients
      treated at the Children's Hospital - London Health Sciences Centre (CH-LHSC)
      between 2002 and 2013 were included in this study. We compared patients
      undergoing surgical intervention with a nonsurgical group with respect to
      demographic characteristics and outcomes. Hospital-associated costs were
      calculated only for the surgical group. RESULTS: Of 784 injured children, 258
      (33%) required surgery, 40% of whom underwent orthopedic interventions. These
      patients were older and more severely injured, and they had longer lengths of
      stay than their nonsurgical counterparts. There was no difference in mortality
      between the groups. Seventy-four surgical patients required intervention within 4
      hours of admission; 45% of them required neurosurgical intervention. The median
      cost of hospitalization was $27 571 for the surgical group. CONCLUSION: One-third
      of pediatric trauma patients required surgical intervention, of whom one-third
      required intervention within 4 hours of arrival. Despite the associated costs,
      the surgical treatment of children was associated with comparable mortality to
      nonsurgical treatment of less severely injured patients. This study represents
      the most recent update to the per patient cost for surgically treated pediatric
      trauma patients in Ontario, Canada, and helps to highlight the multispecialty
      care needed for the management of injured children.

PMID- 29376822
TI  - Suppression and facilitation of human neural responses.
AB  - Efficient neural processing depends on regulating responses through suppression
      and facilitation of neural activity. Utilizing a well-known visual motion
      paradigm that evokes behavioral suppression and facilitation, and combining five
      different methodologies (behavioral psychophysics, computational modeling,
      functional MRI, pharmacology, and magnetic resonance spectroscopy), we provide
      evidence that challenges commonly held assumptions about the neural processes
      underlying suppression and facilitation. We show that: (1) both suppression and
      facilitation can emerge from a single, computational principle - divisive
      normalization; there is no need to invoke separate neural mechanisms, (2) neural
      suppression and facilitation in the motion-selective area MT mirror perception,
      but strong suppression also occurs in earlier visual areas, and (3) suppression
      is not primarily driven by GABA-mediated inhibition. Thus, while commonly used
      spatial suppression paradigms may provide insight into neural response magnitudes
      in visual areas, they should not be used to infer neural inhibition.

PMID- 29376824
TI  - Cell volume changes contribute to epithelial morphogenesis in zebrafish Kupffer's
      vesicle.
AB  - How epithelial cell behaviors are coordinately regulated to sculpt tissue
      architecture is a fundamental question in biology. Kupffer's vesicle (KV), a
      transient organ with a fluid-filled lumen, provides a simple system to
      investigate the interplay between intrinsic cellular mechanisms and external
      forces during epithelial morphogenesis. Using 3-dimensional (3D) analyses of
      single cells we identify asymmetric cell volume changes along the anteroposterior
      axis of KV that coincide with asymmetric cell shape changes. Blocking ion flux
      prevents these cell volume changes and cell shape changes. Vertex simulations
      suggest cell shape changes do not depend on lumen expansion. Consistent with this
      prediction, asymmetric changes in KV cell volume and shape occur normally when KV
      lumen growth fails due to leaky cell adhesions. These results indicate ion flux
      mediates cell volume changes that contribute to asymmetric cell shape changes in
      KV, and that these changes in epithelial morphology are separable from lumen
      generated forces.

PMID- 29376825
TI  - The modulation of neural gain facilitates a transition between functional
      segregation and integration in the brain.
AB  - Cognitive function relies on a dynamic, context-sensitive balance between
      functional integration and segregation in the brain. Previous work has proposed
      that this balance is mediated by global fluctuations in neural gain by
      projections from ascending neuromodulatory nuclei. To test this hypothesis in
      silico, we studied the effects of neural gain on network dynamics in a model of
      large-scale neuronal dynamics. We found that increases in neural gain directed
      the network through an abrupt dynamical transition, leading to an integrated
      network topology that was maximal in frontoparietal 'rich club' regions. This
      gain-mediated transition was also associated with increased topological
      complexity, as well as increased variability in time-resolved topological
      structure, further highlighting the potential computational benefits of the gain
      mediated network transition. These results support the hypothesis that neural
      gain modulation has the computational capacity to mediate the balance between
      integration and segregation in the brain.

PMID- 29376823
TI  - The genome of the Hi5 germ cell line from Trichoplusia ni, an agricultural pest
      and novel model for small RNA biology.
AB  - We report a draft assembly of the genome of Hi5 cells from the lepidopteran
      insect pest, Trichoplusia ni, assigning 90.6% of bases to one of 28 chromosomes
      and predicting 14,037 protein-coding genes. Chemoreception and detoxification
      gene families reveal T. ni-specific gene expansions that may explain its
      widespread distribution and rapid adaptation to insecticides. Transcriptome and
      small RNA data from thorax, ovary, testis, and the germline-derived Hi5 cell line
      show distinct expression profiles for 295 microRNA- and >393 piRNA-producing
      loci, as well as 39 genes encoding small RNA pathway proteins. Nearly all of the
      W chromosome is devoted to piRNA production, and T. ni siRNAs are not 2'-O
      methylated. To enable use of Hi5 cells as a model system, we have established
      genome editing and single-cell cloning protocols. The T. ni genome provides
      insights into pest control and allows Hi5 cells to become a new tool for studying
      small RNAs ex vivo.

PMID- 29376826
TI  - Mitochondria-specific photoactivation to monitor local sphingosine metabolism and
      function.
AB  - Photoactivation ('uncaging') is a powerful approach for releasing bioactive small
      molecules in living cells. Current uncaging methods are limited by the random
      distribution of caged molecules within cells. We have developed a mitochondria
      specific photoactivation method, which permitted us to release free sphingosine
      inside mitochondria and thereafter monitor local sphingosine metabolism by
      lipidomics. Our results indicate that sphingosine was quickly phosphorylated into
      sphingosine 1-phosphate (S1P) driven by sphingosine kinases. In time-course
      studies, the mitochondria-specific uncaged sphingosine demonstrated distinct
      metabolic patterns compared to globally-released sphingosine, and did not induce
      calcium spikes. Our data provide direct evidence that sphingolipid metabolism and
      signaling are highly dependent on the subcellular location and opens up new
      possibilities to study the effects of lipid localization on signaling and
      metabolic fate.

PMID- 29376827
TI  - Activating the regenerative potential of Muller glia cells in a regeneration
      deficient retina.
AB  - Regeneration responses in animals are widespread across phyla. To identify
      molecular players that confer regenerative capacities to non-regenerative species
      is of key relevance for basic research and translational approaches. Here, we
      report a differential response in retinal regeneration between medaka (Oryzias
      latipes) and zebrafish (Danio rerio). In contrast to zebrafish, medaka Muller
      glia (olMG) cells behave like progenitors and exhibit a restricted capacity to
      regenerate the retina. After injury, olMG cells proliferate but fail to self
      renew and ultimately only restore photoreceptors. In our injury paradigm, we
      observed that in contrast to zebrafish, proliferating olMG cells do not maintain
      sox2 expression. Sustained sox2 expression in olMG cells confers regenerative
      responses similar to those of zebrafish MG (drMG) cells. We show that a single,
      cell-autonomous factor reprograms olMG cells and establishes a regeneration-like
      mode. Our results position medaka as an attractive model to delineate key
      regeneration factors with translational potential.

PMID- 29376828
TI  - Portraits of a pressure sensor.
AB  - Near atomic-resolution structures have provided insights into the mechanisms by
      which the Piezo1 ion channel senses and responds to mechanical stimuli.

PMID- 29376830
TI  - Bond-orientational order and Frank's constant in two-dimensional colloidal hard
      spheres.
AB  - Recently, the full phase behaviour of 2D colloidal hard spheres was
      experimentally established, and found to involve a first order liquid to hexatic
      transition and a continuous hexatic to crystal transition (Thorneywork et al 2017
      Phys. Rev. Lett. 118 158001). Here, we expand upon this work by considering the
      behaviour of the bond-orientational correlation time and Frank's constant in the
      region of these phase transitions. We also consider the excess entropy, as
      calculated from the radial distribution functions, for a wide range of area
      fractions covering the liquid, hexatic and crystal phases. In all cases, the
      behaviour of these quantities further corroborates the previously reported
      melting scenario of 2D colloidal hard spheres.

PMID- 29376831
TI  - Topologically-protected one-way leaky waves in nonreciprocal plasmonic
      structures.
AB  - We investigate topologically-protected unidirectional leaky waves on magnetized
      plasmonic structures acting as homogeneous photonic topological insulators. Our
      theoretical analyses and numerical experiments aim at unveiling the general
      properties of these exotic surface waves, and their nonreciprocal and topological
      nature. In particular, we study the behavior of topological leaky modes in
      stratified structures composed of a magnetized plasma at the interface with
      isotropic conventional media, and we show how to engineer their propagation and
      radiation properties, leading to topologically-protected backscattering-immune
      wave propagation, and highly directive and tunable radiation. Taking advantage of
      the non-trivial topological properties of these leaky modes, we also
      theoretically demonstrate advanced functionalities, including arbitrary re
      routing of leaky waves on the surface of bodies with complex shapes, as well as
      the realization of topological leaky-wave (nano)antennas with isolated channels
      of radiation that are completely independent and separately tunable. Our findings
      help shedding light on the behavior of topologically-protected modes in open wave
      guiding structures, and may open intriguing directions for future antenna
      generations based on topological structures, at microwaves and optical
      frequencies.

PMID- 29376829
TI  - TGF-beta uses a novel mode of receptor activation to phosphorylate SMAD1/5 and
      induce epithelial-to-mesenchymal transition.
AB  - The best characterized signaling pathway downstream of transforming growth factor
      beta (TGF-beta) is through SMAD2 and SMAD3. However, TGF-beta also induces
      phosphorylation of SMAD1 and SMAD5, but the mechanism of this phosphorylation and
      its functional relevance is not known. Here, we show that TGF-beta-induced
      SMAD1/5 phosphorylation requires members of two classes of type I receptor,
      TGFBR1 and ACVR1, and establish a new paradigm for receptor activation where
      TGFBR1 phosphorylates and activates ACVR1, which phosphorylates SMAD1/5. We
      demonstrate the biological significance of this pathway by showing that
      approximately a quarter of the TGF-beta-induced transcriptome depends on SMAD1/5
      signaling, with major early transcriptional targets being the ID genes. Finally,
      we show that TGF-beta-induced epithelial-to-mesenchymal transition requires
      signaling via both the SMAD3 and SMAD1/5 pathways, with SMAD1/5 signaling being
      essential to induce ID1. Therefore, combinatorial signaling via both SMAD
      pathways is essential for the full TGF-beta-induced transcriptional program and
      physiological responses.

PMID- 29376832
TI  - Surface charge method for molecular surfaces with curved areal elements I.
      Spherical triangles.
AB  - Parametrizing a curved surface with flat triangles in electrostatics problems
      creates a diverging electric field. One way to avoid this is to have curved areal
      elements. However, charge density integration over curved patches appears
      difficult. This paper, dealing with spherical triangles, is the first in a series
      aiming to solve this problem. Here, we lay the ground work for employing curved
      patches for applying the surface charge method to electrostatics. We show
      analytically how one may control the accuracy by expanding in powers of the the
      arc length (multiplied by the curvature). To accommodate not extremely small
      curved areal elements, we have provided enough details to include higher order
      corrections that are needed for better accuracy when slightly larger surface
      elements are used.

PMID- 29376833
TI  - Ultrahigh lattice thermal conductivity in topological semimetal TaN caused by a
      large acoustic-optical gap.
AB  - Topological semimetals may have potential applications such as in topological
      qubits, spintronics and quantum computations. Efficient heat dissipation is a key
      factor for the reliability and stability of topological semimetal-based nano
      electronics devices, which is closely related to high thermal conductivity. In
      this work, the elastic properties and lattice thermal conductivity of TaN are
      investigated using first-principles calculations and the linearized phonon
      Boltzmann equation within the single-mode relaxation time approximation.
      According to the calculated bulk modulus, shear modulus and C 44, TaN can be
      regarded as a potential incompressible and hard material. The room-temperature
      lattice thermal conductivity is predicted to be 838.62 [Formula: see text] along
      the a axis and 1080.40 [Formula: see text] along the c axis, showing very strong
      anisotropy. It is found that the lattice thermal conductivity of TaN is several
      tens of times higher than other topological semimetals, such as TaAs, MoP and
      ZrTe, which is due to the very longer phonon lifetimes for TaN than other
      topological semimetals. The very different atomic masses of Ta and N atoms lead
      to a very large acoustic-optical band gap, and then prohibit the scattering
      between acoustic and optical phonon modes, which gives rise to very long phonon
      lifetimes. Calculated results show that isotope scattering has little effect on
      lattice thermal conductivity, and that phonons with mean free paths larger than
      20 (80) [Formula: see text] along the c direction at 300 K have little
      contribution to the total lattice thermal conductivity. This work implies that
      TaN-based nano-electronics devices may be more stable and reliable due to
      efficient heat dissipation, and motivates further experimental works to study
      lattice thermal conductivity of TaN.

PMID- 29376834
TI  - Quasi free-standing epitaxial graphene fabrication on 3C-SiC/Si(111).
AB  - Growing graphene on SiC thin films on Si is a cheaper alternative to the growth
      on bulk SiC, and for this reason it has been recently intensively investigated.
      Here we study the effect of hydrogen intercalation on epitaxial graphene obtained
      by high temperature annealing on 3C-SiC/Si(111) in ultra-high vacuum. By using a
      combination of core-level photoelectron spectroscopy, low energy electron
      diffraction, and near-edge x-ray absorption fine structure (NEXAFS) we find that
      hydrogen saturates the Si atoms at the topmost layer of the substrate, leading to
      free-standing graphene on 3C-SiC/Si(111). The intercalated hydrogen fully desorbs
      after heating the sample at 850  degrees C and the buffer layer appears again,
      similar to what has been reported for bulk SiC. However, the NEXAFS analysis
      sheds new light on the effect of hydrogen intercalation, showing an improvement
      of graphene's flatness after annealing in atomic H at 600  degrees C. These
      results provide new insight into free-standing graphene fabrication on SiC/Si
      thin films.

PMID- 29376835
TI  - Broad-spectrum enhanced absorption of graphene-molybdenum disulfide photovoltaic
      cells in metal-mirror microcavity.
AB  - The optical absorption of graphene-molybdenum disulfide photovoltaic cells (GM
      PVc) in wedge-shaped metal-mirror microcavities (w-MMCs) combined with a spectrum
      splitting structure was studied. Results showed that the combination of spectrum
      splitting structure and w-MMC can enable the light absorption of GM-PVcs to reach
      about 65% in the broad spectrum. The influence of processing errors on the
      absorption of GM-PVcs in w-MMCs was 3-14 times lower than that of GM-PVcs in
      wedge photonic crystal microcavities. The light absorption of GM-PVcs reached 60%
      in the broad spectrum, even with the processing errors. The proposed structure is
      easy to implement and may have potentially important applications in the
      development of ultra-thin and high-efficiency solar cells and optoelectronic
      devices.

PMID- 29376836
TI  - Micrometer-sized TPM emulsion droplets with surface-mobile binding groups.
AB  - Colloids coated with lipid membranes have been widely employed for fundamental
      studies of lipid membrane processes, biotechnological applications such as drug
      delivery and biosensing, and more recently, for self-assembly. The latter has
      been made possible by inserting DNA oligomers with covalently linked hydrophobic
      anchors into the membrane. The lateral mobility of the DNA linkers on micrometer
      sized droplets and solid particles has opened the door to creating structures
      with unprecedented structural flexibility. Here, we investigate micro-emulsions
      of TPM (3-(trimethoxysilyl)propyl methacrylate) as a platform for lipid
      monolayers and further functionalization with proteins and DNA oligonucleotides.
      TPM droplets can be produced with a narrow size distribution and are
      polymerizable, thus providing supports for model lipid membranes with controlled
      size and curvature. With fluorescence recovery after photobleaching, we observed
      that droplet-attached lipids, NeutrAvidin proteins, as well as DNA
      oligonucleotides all show mobility on the surface. We explored the assembly of
      micron-sized particles on TPM-droplets by exploiting either avidin-biotin
      interactions or double-stranded DNA with complementary single-stranded end
      groups. While the single molecules are mobile, the particles that are attached to
      them are not. We propose that this is caused by the heterogeneous nature of
      emulsified TPM, which forms an oligomer network that limits the collective motion
      of linkers, but allows the surface mobility of individual molecules.

PMID- 29376837
TI  - Distinguishing quantum dot-like localized states from quantum well-like extended
      states across the exciton emission line in a quantum well.
AB  - We have closely examined the emission spectrum at the heavy-hole exciton
      resonance in a high-quality GaAs multi-quantum well sample using picosecond
      excitation-correlation photoluminescence (ECPL) spectroscopy. Dynamics of the
      ECPL signal at low and high energy sides of the excitonic photoluminescence (PL)
      peak show complementary behavior. The ECPL signal is positive (negative) below
      (above) the PL peak and it changes sign within a narrow band of energy lying
      between the excitonic absorption and emission peaks. The energy at which this
      sign change takes place is interpreted as the excitonic mobility edge as it
      separates localized excitons in quantum dot-like states from mobile excitons in
      quantum well-like states.

PMID- 29376838
TI  - Model observer for assessing digital breast tomosynthesis for multi-lesion
      detection in the presence of anatomical noise.
AB  - Model observers are widely used in task-based assessments of medical image
      quality. The presence of multiple abnormalities in a single set of images, such
      as in multifocal multicentric breast cancer (MFMC), has an immense clinical
      impact on treatment planning and survival outcomes. Detecting multiple breast
      tumors is challenging as MFMC is relatively uncommon, and human observers do not
      know the number or locations of tumors a priori. Digital breast tomosynthesis
      (DBT), in which an x-ray beam sweeps over a limited angular range across the
      breast, has the potential to improve the detection of multiple tumors. However,
      prior studies of DBT image quality all focus on unifocal breast cancers. In this
      study, we extended our 2D multi-lesion (ML) channelized Hotelling observer (CHO)
      into a 3D ML-CHO that detects multiple lesions from volumetric imaging data. Then
      we employed the 3D ML-CHO to identify optimal DBT acquisition geometries for
      detection of MFMC. Digital breast phantoms with multiple embedded synthetic
      lesions were scanned by simulated DBT scanners of different geometries
      (wide/narrow angular span, different number of projections per scan) to simulate
      MFMC cases. With new implementations of 3D partial least squares (PLS) and
      modified Laguerre-Gauss (LG) channels, the 3D ML-CHO made detection decisions
      based upon the overall information from individual DBT slices and their
      correlations. Our evaluation results show that: (1) the 3D ML-CHO could achieve
      good detection performance with a small number of channels, and 3D PLS channels
      on average outperform the counterpart LG channels; (2) incorporating locally
      varying anatomical backgrounds and their correlations as in the 3D ML-CHO is
      essential for multi-lesion detection; (3) the most effective DBT geometry for
      detection of MFMC may vary when the task of clinical interest changes, and a
      given DBT geometry may not yield images that are equally informative for
      detecting MF, MC, and unifocal cancers.

PMID- 29376839
TI  - Exploration of 2-Dimensional Bio-functionalized Phosphorene Nanosheets (Black
      Phosphorous) for Label free Haptoglobin Electro-immunosensing Applications.
AB  - We report on the development of an antibody-functionalized interface based on
      electrochemically active liquid-exfoliated two-dimensional phosphorene (Ph)
      nanosheets-also known as black phosphorous nanosheets-for the label-free
      electrochemical immunosensing of a haptoglobin (Hp) biomarker, a clinical marker
      of severe inflammation. The electrodeposition has been achieved over the screen
      printed electrode (SPE) using liquid-assisted ultrasonically exfoliated black
      phosphorus nanosheets. Subsequently, Ph-SPEs bioconjugated with Hp antibodies
      (Ab), using electrostatic interactions via a poly-L-lysine (PLL) linker for
      biointerface development. Electrochemical analysis demonstrates that the Ab
      modified Ph-SPEs (Ab@Ph-SPE) exhibit enhanced electroconducting behavior as
      compared to the pristine electrodes. This Ab-functionalized phosphorene-based
      electrochemical immunosensor platform has demonstrated remarkable sensitivity and
      specificity, having a dynamic linear response range from 0.01 mg/mL to 10 mg/mL
      for Hp in standard and serum samples with a low detection limit (~0.011 mg/mL)
      using the label-free electrochemical technique. The sensor electrodes were also
      studied with other closely relative interferents to investigate cross reactivity
      and specificity. This strategy opens up avenues to POC (point-of-care) and on
      farm livestock disease monitoring technologies for multiplexed diagnosis in
      complex biological samples such as serum. The technique is simple in fabrication
      and provides an analytical response in less than 60 seconds.

PMID- 29376840
TI  - Growth of wurtzite CdTe nanowires on fluorine-doped tin oxide glass substrates
      and room-temperature bandgap parameter determination.
AB  - The growth of CdTe nanowires, catalyzed by Sn, was achieved on fluorine-doped tin
      oxide glass by physical vapor transport. CdTe nanowires grew along the <0001>
      direction, with a very rare and phase-pure wurtzite structure, at 290  degrees C.
      CdTe nanowires grew under Te-limited conditions by forming SnTe nanostructures in
      the catalysts and the wurtzite structure was energetically favored. By
      polarization-dependent and power-dependent micro-photoluminescence measurements
      of individual nanowires, heavy and light hole-related transitions could be
      differentiated, and the fundamental bandgap of wurtzite CdTe at room temperature
      was determined to be 1.562 eV, which was 52 meV higher than that of zinc-blende
      CdTe. From the analysis of doublet photoluminescence spectra, the valence band
      splitting energy between heavy hole and light hole bands was estimated to be 43
      meV.

PMID- 29376841
TI  - Unidirectional emission in an all-dielectric nanoantenna.
AB  - All-dielectric nanoantennas are a promising alternative to plasmonic optical
      antennas for engineering light emission because of their low-loss nature in the
      optical spectrum. Nevertheless, it is still challenging to manipulate directional
      light emission with subwavelength all-dielectric nanoantennas. Here, we propose
      and numerically demonstrate that a hollow silicon nanodisk can serve as a
      versatile antenna for directing and enhancing the emission from either an
      electric or magnetic dipole emitter. When primarily coupled to both electric and
      magnetic dipole modes of a nanoantenna, broadband nearly-unidirectional emission
      can be realized by the interference of two modes, which can be spectrally tuned
      via the geometric parameters in an easy way. More importantly, the emission
      directions for the magnetic and electric dipole emitters are shown as opposite to
      each other through control of the phase difference between the induced magnetic
      and electric dipole modes of the antenna. Meanwhile, the Purcell factors can be
      enhanced by more than one order of magnitude and high quantum efficiencies can be
      maintained at the visible spectrum for both kinds of dipole emitters. We further
      show that these unidirectional emission phenomena can withstand small disorder
      effects of in-plane dipole orientation and location. Our study provides a simple
      yet versatile platform that can shape the emission of both magnetic and electric
      dipole emitters.

PMID- 29376842
TI  - Diameter-tailored telecom-band luminescence in InP/InAs heterostructure nanowires
      grown on InP (111)B substrate with continuously-modulated diameter from
      microscale to nanoscale.
AB  - We report diameter-tailored luminescence in telecom band of InP/InAs multi
      heterostructure nanowires with continuously-modulated diameter from microscale to
      nanoscale. By using the self-catalyzed vapor-solid-liquid approach, we tune the
      indium particle size, and consequently the InP/InAs nanowire diameter, during
      growth by modulating the flow rate of the indium source material. This technique
      allows a high degree of continuous tuning in a wide scale from microscale to
      nanoscale. Hence it offers an original way to bridge the gap between microscale
      featured photolithographic and nanoscale-featured nanolithographic processes and
      to incorporate InAs quantum disks with tunable diameters into a single InP/InAs
      quantum heterostructure nanowire. We realized site-defined nanowires with
      nanoscale diameters initiated from site-defined microscale-diameter particles
      made with a conventional photolithographic process. The luminescence wavelength
      from InAs quantum disks is directly connected to the nanowire diameter, by which
      the strain in the InAs quantum disks is tailored. This work provides new
      opportunities in the fabrication and design of nanowire devices that extends
      beyond what is achievable with the current technologies and enables the nanowire
      shape to be engineered thus offering the potential to broaden the application
      range of nanowire devices.

PMID- 29376843
TI  - Isolated metachronous breast metastasis from renal cell carcinoma: A report of
      two cases.
AB  - Metastases to the breast are very uncommon as compared to primary tumours. Breast
      is an unusual site for metastasis from renal cell carcinoma. Only occasional
      cases are reported in the literature. These metastases must be clearly diagnosed
      as the treatment of primary breast cancer and metastases differs markedly.
      Treatment of isolated metastases from renal cell carcinoma is usually surgical
      resection. We report two cases of isolated metachronous metastases to breast from
      renal cell carcinoma.

PMID- 29376844
TI  - Clinico-pathologic disparities of breast cancer in Hispanic/Latina women.
AB  - BACKGROUND: Breast cancer is the leading cause of cancer death in Hispanic/Latina
      women nationwide. Limited cancer research has been conducted in this population.
      El Paso, Texas is a large border city with a population of around 900,000, of
      which 85% are Latinos and would provide a suitable setting for this study. The
      aim of this study is to evaluate ethnic differences and cancer characteristics in
      Hispanic/latina women with breast cancer. METHODS: After IRB approval, we
      retrospectively analyzed the variables of patients with breast cancer treated
      consecutively at a large tertiary medical center in El Paso, TX between 2005
      2015. Descriptive statistics, bivariate, and multivariable analyses were
      conducted. RESULTS: 1,252 patients were identified. Mean age at diagnosis was 57
      years. 1074 were Hispanics/Latinas (86%). When comparing Hispanics versus non
      Hispanics, 31% of Hispanics compared to 24% Non-Hispanics were diagnosed at age
      <50 (P = 0.043). More Hispanics are uninsured (34%) compared to Non-Hispanics
      (25%) (p = 0.008). Hispanics presenting with advanced stages were more likely to
      be uninsured (P = 0.02). CONCLUSIONS: This analysis confirms that
      Hispanics/Latinas are diagnosed with breast cancer at a younger age and are more
      commonly uninsured than Non-Hispanics. We did not observe significant differences
      in the prevalence of ER+, triple negative or Her2 -neu positive disease or stages
      at presentation between the 2 groups in this cohort, however the non-Hispanic
      group was constituted only 14% of the studied population. A larger multi
      institutional comparative study is being conducted to confirm these findings.

PMID- 29376845
TI  - Articular cartilage response to a sliding load using two different-sized
      spherical indenters1.
AB  - BACKGROUND: Cartilage surface contact geometry influences the deformational
      behavior and stress distribution throughout the extracellular matrix (ECM) under
      load. OBJECTIVE: To test the correlation between the mechanical and cellular
      response of articular cartilage when loaded with two different-sized spherical
      indenters under dynamic reciprocating sliding motion. METHODS: Articular
      cartilage explants were subjected to a reciprocating sliding load using a 17.6 mm
      or 30.2 mm spherical ball for 2000 cycles at 10 mm/s and 4 kg axial load.
      Deformation of the cartilage was recorded and contact parameters were calculated
      according to Hertzian theory. After mechanical loading cartilage samples were
      collected and analyzed for ECM collagen damage, gene regulation and proteoglycan
      (PG) loss. RESULTS: Significantly higher ECM deformation and strain and lower
      dynamic effective modulus were found for explants loaded with the smaller
      diameter indenter whereas contact radius and stress remained unaffected. Also,
      the 17.6 mm indenter increased PG loss and significantly upregulated genes for
      ECM proteins and enzymes as compared to the 30.2 mm indenter. CONCLUSION: Sliding
      loads that increase ECM deformation/strain were found to induce enzyme-mediated
      catabolic processes in articular cartilage explants. These observations provide
      further understanding of how changes in cartilage contact mechanics under dynamic
      conditions can affect the cellular response.

PMID- 29376846
TI  - Remodeling of the arterial wall: Response to restoration of normal blood flow
      after flow reduction.
AB  - BACKGROUND: Although many studies have shown that arteries change diameter in
      response to chronic change in blood flow (BF), keeping wall shear stress (WSS) at
      physiologically normal levels, relatively little is known about the effects of
      flow restoration after flow reduction and also the role of vascular smooth muscle
      (VSM) during such a remodeling process. OBJECTIVE: To elucidate the biomechanical
      responses of the arterial wall to the restoration of normal BF after flow
      reduction and compare the results with our previous results observed in response
      to decreased BF alone. METHODS: Carotid artery BF in the Wistar rat was decreased
      by ligation and then restored to normal levels by release of the ligation. The
      effects of BF changes on the biomechanical properties of the carotid arterial
      wall were determined from measurements of diameters and pressures of excised
      artery segments. RESULTS: During BF reduction and restoration, WSS was maintained
      at physiological levels by changes in the internal diameter. No significant
      changes in the incremental elastic modulus were found in response to changes in
      BF. VSM tone was significantly enhanced during the changes in BF. CONCLUSIONS:
      Arteries change diameters in response to BF reduction and also flow restoration
      to normal after flow reduction, keeping WSS at physiologically normal levels. The
      lack of changes in vascular elasticity suggests that there were no significant
      changes in major wall constituents, such as elastin and collagen. VSM may play
      the dominant role in observed arterial remodeling and adaptation.

PMID- 29376847
TI  - Early Stage Alterations in CA1 Extracellular Region Proteins Indicate
      Dysregulation of IL6 and Iron Homeostasis in the 5XFAD Alzheimer's Disease Mouse
      Model.
AB  - In recent years, an increasing number of research papers revealed that the
      compositional and volumetric alterations in the extracellular matrix are the
      consequences of aging and may be related to Alzheimer's disease (AD). In this
      study, we aimed to demonstrate the alterations in hippocampal extracellular fluid
      proteins in vivo using the 5XFAD mouse model. Samples were obtained from
      hippocampi of 5XFAD mice (n = 6) and their non-transgenic littermates by
      intracerebral push-pull perfusion technique at 3 months of age, representing the
      pre-pathological stage of the AD. Proteins in the hippocampal perfusates were
      analyzed by Ultra Performance Liquid Chromatography-Electrospray Ionization
      Quadrupole Time-of-Flight Mass Spectrometry (UPLC-ESI-qTOF-MS/MS). 178 proteins
      were identified and 19 proteins of them were found to be statistically
      significantly altered (p<=0.05, fold change >=40%, unique peptide count >=3) in
      the hippocampal CA1 extracellular fluid of the 5XFAD mouse model. Ingenuity
      pathway analysis of the protein expression results identified IL6 as an upstream
      regulator. The upregulation of IL6 was validated by immunohistochemical staining
      of the hippocampus and cortex of the 5XFAD mice prior to Abeta plaque formation.
      Furthermore, the iron level in the hippocampus was measured by inductively
      coupled plasma-mass spectrometry as IL6 is mentioned in several studies to take
      part in iron homeostasis and inflammation and found to be increased in 5XFAD mice
      hippocampus. Alterations in extracellular matrix proteins in addition to
      increasing amount of hippocampal IL6 and iron in the early stages of AD may
      reveal inflammation-mediated iron dyshomeostasis in the early stages of
      neurodegeneration.

PMID- 29376848
TI  - Drugs for Dementia and Excess of Hospitalization: A Longitudinal French Study.
AB  - BACKGROUND: The impact of adverse effects of drugs for dementia on the risk of
      hospitalization has not been much studied despite the impact of hospitalizations
      on cognitive decline. OBJECTIVE: To determine if the main adverse effects of
      cholinesterase inhibitors and memantine may be associated with excess of
      hospitalization and to quantify the subsequent impact on healthcare expenditures.
      METHODS: A representative sample of the French national health insurance
      beneficiaries aged 65 and older and suffering from dementia were included and
      followed from 2007 to 2014. Binary logit models for longitudinal data (GEE
      estimation technique) were used to estimate the excess of hospitalization events
      related to the adverse effects of anti-dementia drugs and then to derive the
      additional costs of hospitalizations for the public health insurance fund.
      RESULTS: In total, 7,668 patients were followed, generating 111,133 individual
      observations over the 8-year period. Treated patients were hospitalized
      significantly more than non-treated patients (adjusted Odd Ratio (OR) = 1.08, 95%
      confidence interval (95% CI) = [1.02 to 1.13], p = 0.004), mainly with
      cholinesterase inhibitors for cardiac (OR = 1.21, 95% CI = [1.01 to 1.46], p =
      0.034) and gastrointestinal events (OR = 1.43, 95% CI = [1.01-2.05], p = 0.045),
      especially with rivastigmine. When extrapolated to the entire population, this
      corresponded to an annual additional cost of ? 55,000. CONCLUSION: Prescription
      of antidementia drugs, more specifically rivastigmine, increases the risk of
      hospitalizations via their cardiac and gastrointestinal adverse effects and lead
      to additional health care expenditures. Even though these results must be
      confirmed, they may encourage cautious consideration of the balance between
      benefits and harms before a prescription is given.

PMID- 29376849
TI  - Progression of Alzheimer's Disease-Related Pathology and Cell Counts in a Patient
      with Idiopathic Normal Pressure Hydrocephalus.
AB  - We had an opportunity to assess the change observed in the brain regarding
      Alzheimer's disease (AD)-related alterations, cell count, and inflammation that
      took place during a period of 21 months in a subject with a definite diagnosis of
      AD and idiopathic Normal Pressure Hydrocephalus (iNPH). Four neuronal markers,
      i.e., synaptophysin, microtubule associated protein 2, non-phosphorylated
      neurofilament H (SMI32), and embryonic lethal abnormal visual system proteins 3/4
      HuC/HuD (HuC/HuD); three microglial markers CD68, Human Leucocytic Antigen DR,
      ionized calcium-binding adaptor molecule 1, glial fibrillary acidic protein
      (GFAP); and AD-related markers, hyperphosphorylated tau (HPtau) and amyloid-beta
      (Abeta, Abeta40, Abeta42) were assessed. Morphometrically assessed
      immunoreactivity of all neuronal and all microglial markers and Abeta42 decreased
      parallel with an increase in the HPtau in the frontal cortex. The expression of
      GFAP was stable with time. The first sample was obtained during the therapeutic
      shunting procedure for iNPH, and the second sample was obtained postmortem.
      Negligible reactive changes were observed surrounding the shunt channel. In
      conclusion, in the late stage of AD with time, a neuronal loss, increase in the
      HPtau, and decrease in Abeta42 and microglia was observed, whereas the expression
      of GFAP was rather stable. The observations described here suggest that when a
      brain biopsy has been obtained from an adult subject with iNPH, the assessment of
      postmortem brain is of major significance.

PMID- 29376850
TI  - A Link between Subjective Perceptions of Memory and Physical Function:
      Implications for Subjective Cognitive Decline.
AB  - Subjective impairment in memory is a frequently defining feature of subjective
      cognitive decline (SCD), a state hypothesized to precede objectively apparent
      cognitive symptoms of Alzheimer's disease (AD) and to hold promise as a non
      invasive, inexpensive, preclinical indicator of AD. However, a full model of the
      factors that contribute to subjective memory (SM), and therefore to SCD, has yet
      to be articulated. While SM impairment is widely known to be associated with
      negative affect, the extent to which SM functioning may also reflect other
      factors, particularly subjective beliefs or perceptions about one's health, is
      not known. To examine the extent to which SM is associated with subjective
      perceptions of health more broadly, the current study investigated the link
      between SM and subjective physical functioning (independent of depressive affect,
      and objective cognitive and physical function) in an ethnically diverse sample of
      471 older adults enrolled in the population-based Northern Manhattan Aging
      Project. 199 (42%) participants endorsed no difficulty on a 5-point SM index
      while 272 (58%) endorsed some degree of difficulty. As hypothesized, SM
      correlated with both depression and subjective physical function, but not with
      age, education, global cognition, or objective physical function. When objective
      and subjective physical function were entered in two separate, adjusted linear
      regressions predicting SM, only subjective physical function and depressive
      affect independently predicted SM. Subjective perceptions of memory appear to
      reflect individuals' broader health perceptions in part. Articulating the various
      correlates of SM will improve identification of SCD specific to preclinical AD.

PMID- 29376851
TI  - Validation of the Delayed Matching-to-Sample Task 48 (DMS48) in Elderly Chinese.
AB  - BACKGROUND: Delayed Matching-to-Sample Task 48 (DMS48), a brief tool measuring
      visual recognition memory, is valid to identify the early stage of Alzheimer's
      disease (AD) in Caucasians. However, little data is available in Chinese.
      OBJECTIVE: To develop norms and optimal cutoff points for the DMS48 in Chinese
      elders. METHODS: A cross-sectional study was conducted in seven memory clinics
      from five cities across China. DMS48 was applied to 369 Chinese aged 50 or older
      (138 cognitively normal [CN], 112 mild cognitive impairment due to AD (MCI-A),
      and 119 mild AD dementia). The demographic factors which influence DMS48 scores
      were investigated and the norms were established considering those factors.
      Receiver operating characteristic (ROC) analysis was used to determine the
      optimal cutoff points. RESULTS: Age was shown to influence DMS48 scores (r = 
      0.36, p < 0.05), and we presented the age-stratified normative data for the
      DMS48. The optimal cutoff point is 42/43 for identifying cognitive impairment
      (MCI-A and AD dementia) against CN (sensitivity 97.80% and specificity 89.13%)
      and MCI-A against CN (sensitivity 86.60% and specificity 94.20%). A cutoff of
      39/40 obtained good sensitivity (100.00%) and specificity (94.90%) in
      discriminating AD dementia from CN. The age-stratified optimal cutoff points for
      identifying MCI-A were 43/44 for individuals aged 50 to 59 years old, 42/43 for
      60 to 69 years old, 41/42 for 70 to 79 years old, and 40/41 for 80 or older,
      respectively (sensitivity 84.80% and specificity 95.70%). CONCLUSION: This study
      proved that DMS48 is of good validation in screening MCI-A in elderly Chinese.

PMID- 29376852
TI  - Structural Connectivity Alterations Along the Alzheimer's Disease Continuum:
      Reproducibility Across Two Independent Samples and Correlation with Cerebrospinal
      Fluid Amyloid-beta and Tau.
AB  - BACKGROUND: Gray matter changes associated with the progression of Alzheimer's
      disease (AD) have been thoroughly studied. However, alterations in white matter
      tracts have received less attention, particularly during early or preclinical
      stages of the disease. OBJECTIVE: To identify the structural connectivity changes
      across the AD continuum. METHODS: We performed probabilistic tractography in a
      total of 183 subjects on two independent samples that include control (n = 68)
      and preclinical AD individuals (n = 28), patients diagnosed with mild cognitive
      impairment (MCI) due to AD (n = 44), and AD patients (n = 43). We compared the
      connectivity between groups, and with CSF Abeta42 and tau biomarkers. RESULTS: We
      observed disconnections in preclinical individuals, mainly located in the
      temporal lobe. This pattern of disconnection spread to the parietal and frontal
      lobes at the MCI stage and involved almost all the brain in AD. These findings
      were not driven by gray matter atrophy. DISCUSSION: Using tractography, we were
      able to identify white matter changes between subsequent disease stages and,
      notably, also in preclinical AD. Therefore, this method may be useful for
      detecting early and specific brain structural changes during preclinical AD
      stage.

PMID- 29376853
TI  - The Impact of APOE E4 in Alzheimer's Disease Differs According to Age.
AB  - We evaluated how the impact of apolipoprotein E4 (APOE4) differs according to age
      in Alzheimer's disease (AD) patients. We recruited 846 AD patients and 815
      cognitively normal controls and categorized into three groups with respect to
      their age (<65, 65-74, and >=75 years). We evaluated the risk of AD in APOE4
      carriers and compared cortical thickness and cognitive function according to
      APOE4 status in each age group. At the point of this study, in young (<65 years)
      AD, APOE4 noncarriers had the most severe frontal and perisylvian atrophy, while
      in old (>=75 years) AD, APOE4 carriers had the most severe medial temporal
      atrophy. In AD under 75 years, APOE4 noncarriers and heterozygotes showed worse
      performance in language, visuospatial, and frontal function compared to
      homozygotes, while, in old (>=75 years) AD, APOE4 homozygotes showed worse
      performance in memory compared to noncarriers. As the detrimental effects of
      APOE4 seen in older AD patients were not found in younger AD patients, we suggest
      that some unrevealed factors are associated with cortical atrophy and non
      amnestic cognitive dysfunction in young AD with APOE4 noncarriers.

PMID- 29376854
TI  - Detection of Dementia Cases in Two Swedish Health Registers: A Validation Study.
AB  - BACKGROUND: Population-based health registers are potential assets in
      epidemiological research; however, the quality of case ascertainment is crucial.
      OBJECTIVE: To compare the case ascertainment of dementia, from the National
      Patient Register (NPR) and the Cause of Death Register (CDR) with dementia
      diagnoses from six Swedish population based studies. METHODS: Sensitivity,
      specificity, and positive predictive value (PPV) of dementia identification in
      NPR and CDR were estimated by individual record linkage with six Swedish
      population based studies (n = 19,035). Time to detection in NPR was estimated
      using data on dementia incidence from longitudinal studies with more than two
      decades of follow-up. RESULTS: Barely half of the dementia cases were ever
      detected by NPR or CDR. Using data from longitudinal studies we estimated that a
      record with a dementia diagnosis appears in the NPR on average 5.5 years after
      first diagnosis. Although the ability of the registers to detect dementia cases
      was moderate, the ability to detect non-dementia cases was almost perfect (99%).
      When registers indicate that there is a dementia diagnosis, there are very few
      instances in which the clinicians determined the person was not demented. Indeed,
      PPVs were close to 90%. However, misclassification between dementia subtype
      diagnoses is quite common, especially in NPR. CONCLUSIONS: Although the overall
      sensitivity is low, the specificity and the positive predictive value are very
      high. This suggests that hospital and death registers can be used to identify
      dementia cases in the community, but at the cost of missing a large proportion of
      the cases.

PMID- 29376855
TI  - SORL1 Variants in Familial Alzheimer's Disease.
AB  - The SORL1 gene encodes a protein involved in the amyloidogenic process, and its
      variants have been associated with Alzheimer's disease (AD) physiopathology. We
      screened for SORL1 variants in 124 familial (44 early- and 80 late-onset)
      dementia of Alzheimer type (DAT) cases. Nine potentially pathogenic changes
      (three not previously reported and six rare variants) were found in nine probands
      (7%). After screening the control population and siblings (presence in at least
      1/200 controls and/or absence of segregation pattern), a causal relationship with
      the disease was considered unlikely in six variants and uncertain in one. The
      change Trp848Ter and a splice-site variant remained likely correlated with the
      disease. SORL1 mutations are present in 7% of our familial DAT cohort, though in
      most cases cannot be considered the direct cause of the disease.

PMID- 29376856
TI  - In vivo Depiction of alpha7 Nicotinic Receptor Loss for Cognitive Decline in
      Alzheimer's Disease.
AB  - BACKGROUND: The alpha7 subtype of the nicotinic acetylcholine receptor (nAChR) is
      considered important in higher cognitive functions, and cholinergic loss
      underpins the pathophysiology of Alzheimer's disease (AD). However, the
      relationships between alpha7 nAChR function and clinical functions or amyloid
      beta (Abeta) deposition remain to be explored in the living AD brain. OBJECTIVE:
      We aimed to elucidate the relationship between alpha7 nAChR availability in the
      specific cholinergic region and cognitive decline in the Abeta-confirmed AD
      brain. METHODS: Twenty AD patients and ten age-matched healthy subjects were
      examined. The alpha7-nAChR availability and Abeta deposition were evaluated using
      positron emission tomography with an alpha7 nAChR radiotracer 11C-(R)-MeQAA and
      11C-Pittsburg compound B (11C-PiB), respectively. Semi-quantified values of
      tracer binding were estimated with a simplified reference tissue method for BPND
      of 11C-(R)-MeQAA and a tissue ratio method for SUVR of 11C-PiB. These parameters
      and clinical scores were compared voxel-wise using a statistical parametric
      mapping method. RESULTS: The levels of 11C-(R)-MeQAA BPND in the temporal and
      prefrontal cholinergic projection regions were significantly lower in AD, and
      negative correlations were found between 11C-PiB SUVR and 11C-(R)-MeQAA BPND in
      the region of the nucleus basalis magnocellularis and medial prefrontal cortex.
      Levels of 11C-(R)-MeQAA BPND were significantly correlated with memory and
      frontal function scores in AD. CONCLUSION: The association between Abeta burden
      and alpha7-nAChR reduction in the basal forebrain cholinergic system was
      highlighted in relation to cognitive decline in AD. This suggests that Abeta
      linked alpha7-nAChR reduction is clinico-pathophyisologically important for
      considering a good therapeutic target in AD.

PMID- 29376858
TI  - Exercise Training on Locomotion in Patients with Alzheimer's Disease: A
      Feasibility Study.
AB  - BACKGROUND: Although current literature has shown that patients with Alzheimer's
      disease (AD) have worse locomotion compared with healthy counterparts, no studies
      have focused on the efficacy of exercise training in improving gait abnormalities
      including biomechanics and metabolic aspects, in this population. OBJECTIVE: To
      verify the effectiveness of exercise training (ET) on gait parameters (i.e.,
      speed, step and stride length, single and double support, and energy cost of
      walking (Cw)) in patients with AD with respect to a standard cognitive treatment
      (CT). METHODS: In this study, we included a small portion of data belonging to a
      larger study (ClinicalTrials.gov number, NCT03034746). Patients with AD (Mini
      Mental State Examination 22+/-5) were included in the study. Gait parameters and
      Cw were assessed at baseline and after 6 months (72 treatment sessions) of
      treatment. ET included 90 min of aerobic and strength training. CT included 90
      min of cognitive stimuli. RESULTS: The 16 patients assigned to ET exhibited
      significant improvement of Cw (-0.9+/-0.1 J/kg.m-1), while differences in gait
      parameters were negligible. The effect on gait parameters were undetectable in
      the 18 patients assigned to CT (-0.2+/-0.5 J/kg.m-1). CONCLUSIONS: Data from this
      study showed that ET program seems effective in improving Cw in patients with AD.
      Interestingly, the positive effect of ET on Cw was not coupled with ameliorations
      of patient's gait parameters, suggesting that the gain of metabolic aspects of
      locomotion were the main factors responsible for this positive result.

PMID- 29376859
TI  - Dysregulation and Dislocation of SFPQ Disturbed DNA Organization in Alzheimer's
      Disease and Frontotemporal Dementia.
AB  - SFPQ (Splicing factor proline- and glutamine-rich) is a DNA and RNA binding
      protein involved in transcription, pre-mRNA splicing, and DNA damage repair. SFPQ
      was found dysregulated in a few tauopathies such as Alzheimer's disease (AD) and
      frontotemporal dementia (FTD). In addition, knock-down of SFPQ induced FTD-like
      behavior in mouse. To confirm the role of SFPQ in AD and FTD, we analyzed the
      brain sections from the AD and FTD brain samples with SFPQ upregulation and
      dislocation. Specifically, we observed SFPQ dislocated to the cytoplasm and
      nuclear envelopes, and DNA structures and organizations were associated with
      these dislocation phenotypes in AD and FTD brains. Consistently, we also found
      decreased DAPI intensities and smaller chromocenters associated with SFPQ
      dislocation in nerural-2a (N2a) cells. As the upregulation and
      hyperphosphorylation of tau protein is a hallmark of AD and FTD, our study sought
      to investigate potential interactions between tau and SFPQ by co-transfection and
      co-immunoprecipitation assays in N2a cells. SFPQ dislocation was found enhanced
      with tau co-transfection and tau co-transfection further resulted in extended DNA
      disorganization in N2a cells. Overall, our results indicate that dysregulation
      and dislocation of SFPQ and subsequent DNA disorganization might be a novel
      pathway in the progression of AD and FTD.

PMID- 29376860
TI  - Mutation Screening of the CHCHD2 Gene for Alzheimer's Disease and Frontotemporal
      Dementia in Chinese Mainland Population.
AB  - As an important multifunctional protein involved in regulation of mitochondrial
      metabolism, CHCHD2 was identified as a causative gene for Parkinson's disease
      (PD), yet the relationship between CHCHD2 and neurodegenerative dementia is not
      well understood. We directly sequenced the entire coding region of CHCHD2 gene in
      150 AD patients, 84 FTD patients, and 417 controls. Four rare putative pathogenic
      variants of CHCHD2, including rs142444896 (c.5C>T, p.P2L), rs752705344 (c.15C>G,
      p.S5R), rs145190179 (c.94G>A, p.A32T), and rs182992574 (c.255T>A, p.S85R) were
      identified from a cohort composed of 150 AD and 84 FTD patients. These results
      suggest that CH CHD2 gene play an important role in other neurodegenerative
      disorders from our dementia study in China.

PMID- 29376861
TI  - The Progression of Neuropsychiatric Symptoms in Alzheimer's Disease During a Five
      Year Follow-Up: Kuopio ALSOVA Study.
AB  - BACKGROUND: An improved understanding of the role of neuropsychiatric symptoms
      (NPS) in the course of Alzheimer's disease (AD) has recently emerged. NPS lead to
      hospitalization and caregiver stress, but are more variable during the course of
      the disease than other symptoms. Knowledge about the role of specific NPS in
      disease progression and prognosis is especially limited. OBJECTIVES: To examine
      the relationship between specific NPS and AD severity during a 5-year follow-up
      period, and to determine which baseline NPS predict AD progression. METHODS: 236
      persons with very mild (CDR 0.5) or mild (CDR 1) AD at baseline and their
      caregivers were followed up for five years as part of the ALSOVA study. The
      Neuropsychiatric Inventory was used to assess NPS, and AD severity progression
      was measured with the Clinical Dementia Rating Sum of Boxes. Data was analyzed
      with Generalized Estimated Equations and Linear Mixed Models. RESULTS: The
      baseline NPS that best predicted AD progression were delusions, agitation, and
      aberrant motor behavior, while AD severity during follow-up was associated with
      hallucinations, delusions, agitation, apathy, aberrant motor behavior, and sleep
      and appetite disturbances. CONCLUSIONS: Persons with mild AD presenting
      delusions, agitation, and aberrant motor behavior at the time of diagnosis could
      have a more rapidly progressing disease, and some NPS are associated with AD
      severity. These results highlight the importance of evaluating NPS at the time of
      AD diagnosis, and the need to offer additional support to persons presenting
      delusions, agitation and aberrant motor behavior, and their caregivers.

PMID- 29376862
TI  - Humanin Exerts Neuroprotection During Cardiac Ischemia-Reperfusion Injury.
AB  - Cardiac ischemia-reperfusion (I/R) injury has been shown to impair brain
      function. Humanin analogue (HNG) given prior to cardiac ischemia has been shown
      to attenuate both heart and brain mitochondrial dysfunction caused by cardiac I/R
      injury. In a clinical setting, patients received medical treatment for acute
      myocardial infarction either during or after the onset of myocardial ischemia;
      thus, in this study, we tested the hypothesis that the administration of HNG
      during cardiac I/R injury has therapeutic potential for brain protection. Thirty
      six male Wistar rats were divided into two groups: a cardiac I/R group (n = 30),
      and a sham group (n = 6). The I/R rats were then divided into five subgroups to
      receive: 1) vehicle; 2) HNG (84 MUg/kg); 3) HNG (168 MUg/kg); 4) HNG (252 MUg/kg)
      intravenously administered during the cardiac-ischemia; and 5) HNG at 252 MUg/kg
      given at the onset of reperfusion. At the end of treatment, brains were removed
      for determination of blood-brain barrier (BBB) breakdown, oxidative stress, brain
      mitochondrial function, brain mitochondrial dynamics, p-tau, amyloid-beta (Abeta)
      and apoptosis. HNG at a dose of 168 and 252 MUg/kg administered during ischemia,
      and 252 MUg/kg given at the onset of reperfusion effectively attenuated the brain
      mitochondrial dysfunction, tau hyperphosphorylation and Abeta accumulation, and
      apoptosis, without reducing BBB breakdown, brain oxidative stress, or
      mitochondrial dynamic, caused by cardiac I/R injury. In conclusion, humanin
      exerted neuroprotection during induced cardiac I/R injury via improvement in
      brain mitochondrial function, and the reduction of Alzheimer's disease pathology
      and apoptosis.

PMID- 29376863
TI  - Altered Expression of Circulating Cdc42 in Frontotemporal Lobar Degeneration.
AB  - The term frontotemporal lobar degeneration (FTLD) defines a group of
      heterogeneous conditions histologically characterized by neuronal degeneration,
      inclusions of various proteins, and synaptic loss. However, the molecular
      mechanisms contributing to these alterations are still unknown. As the Rho-GTPase
      family member Cell division cycle 42 (Cdc42) plays a key role in the regulation
      of actin cytoskeleton dynamics and spine formation, we investigated whether Cdc42
      protein levels were altered in the disease. Cdc42 was increased in the frontal
      cortex of FTLD patients compared to age-matched controls, but also in Alzheimer's
      disease (AD) patients included in the data-set. On the other hand, the pool of
      circulating Cdc42 in the plasma was altered in FTLD but not in AD patients.
      Interestingly, the stratification of the FTLD patients according to the different
      clinical variants showed a specific decrease of Cdc42 expression in the
      behavioral subgroup. This data support a role of Cdc42 in FTLD and specifically
      in the behavioral variant.

PMID- 29376864
TI  - The Effects and Meanings of Receiving a Diagnosis of Mild Cognitive Impairment or
      Alzheimer's Disease When One Lives Alone.
AB  - BACKGROUND: One third of older adults with cognitive impairment live alone and
      are at high risk for poor health outcomes. Little is known about how older adults
      who live alone experience the process of receiving a diagnosis of mild cognitive
      impairment (MCI) or Alzheimer's disease (AD). OBJECTIVE: The aim of this study
      was to understand the effects and meanings of receiving a diagnosis of MCI or AD
      on the lived experience of older adults living alone. METHODS: This is a
      qualitative study of adults age 65 and over living alone with cognitive
      impairment. Participants' lived experiences were elicited through ethnographic
      interviews and participant observation in their homes. Using a qualitative
      content analysis approach, interview transcripts and fieldnotes were analyzed to
      identify codes and themes. RESULTS: Twenty-nine older adults and 6 members of
      their social circles completed 114 ethnographic interviews. Core themes included:
      relief, distress, ambiguous recollections, and not knowing what to do.
      Participants sometimes felt uplifted and relieved by the diagnostic process. Some
      participants did not mention having received a diagnosis or had only partial
      recollections about it. Participants reported that, as time passed, they did not
      know what to do with regard to the treatment of their condition. Sometimes they
      also did not know how to prepare for a likely worsening of their condition, which
      they would experience while living alone. CONCLUSION: Findings suggest the need
      for more tailored care and follow-up as soon as MCI or AD is diagnosed in persons
      living alone.

PMID- 29376866
TI  - Dilated Perivascular Spaces in the Centrum Semiovale Begin to Develop in Middle
      Age.
AB  - BACKGROUND: Dilated perivascular spaces in the centrum semiovale (CSO-PVS) are
      closely related to small vessel disease. However, recent studies have revealed
      that cerebral amyloid angiopathy can cause dilation of the CSO-PVS and
      obstruction of interstitial fluid flow along the intramural periarterial
      drainage. OBJECTIVE: To examine the severity and age-related prevalence of CSO
      PVS through magnetic resonance imaging (MRI) and investigate their clinically
      relevant factors. METHODS: This study included 1,060 subjects who participated in
      our brain program. The subjects ranged from 23 to 83 years in age and were active
      in society. The frequencies of the MRI abnormalities of small vessel diseases,
      including CSO-PVS, were examined. The CSO-PVS severity was classified into three
      grades: G0, G1, G2, according to the visual rating. The subjects were divided
      into five age groups and their age-related frequencies were also studied. Using
      the clinico-laboratory data of 712 subjects, the clinically relevant factors of
      CSO-PVS were investigated using logistic regression analysis. RESULTS: The
      frequencies of all G0 ("normal") MRI abnormalities significantly decreased with
      age. A high prevalence of G2 CSO-PVS was observed (24%) in the youngest group
      aged<=39 years, whereas other MRI abnormalities in this group were not or rarely
      observed. In multivariable logistic regression analyses, G2 CSO-PVS was found to
      be closely associated with age, hypertension, and the estimated glomerular
      filtration ratio. CONCLUSIONS: This study reveals that CSO-PVS begin to develop
      in subjects aged less than 39 years. Age-related changes are involved. Further
      studies are necessary to elucidate the pathophysiological role of the CSO-PVS.

PMID- 29376865
TI  - Associations of Dietary Protein and Fiber Intake with Brain and Blood Amyloid
      beta.
AB  - Accumulating evidence suggests a diet high in protein and fiber may confer some
      protection against Alzheimer's disease (AD). However, no human studies to-date
      have assessed the relationship between protein and fiber intake, and plasma and
      brain amyloid-beta (Abeta). Consequently, this cross-sectional study,
      investigated the association of self-reported dietary intakes of protein and
      fiber, with plasma and brain Abeta burden (n = 541, and n = 162 respectively), in
      a well-characterized cohort of cognitively normal older adults, drawn from the
      larger Australian Imaging, Biomarkers and Lifestyle (AIBL) study of aging. We
      observed 12.59 and 8.43 higher odds of 'high' brain Abeta burden (PiB PET
      SUVR>=1.5) if protein intake fell in the lowest and middle tertile, respectively,
      compared to the highest tertile (p = 0.008; p = 0.013). Thus, in this cohort, the
      more protein consumed, the less likelihood of 'high' Abeta burden in the brain.
      No other significant associations were observed. The results of this study
      highlight the potentially protective impact of high dietary protein intake on
      brain Abeta burden in older adults, before objective memory decline is apparent.
      While longitudinal validation is required, these findings may assist in the
      development of dietary approaches aimed at preventing or delaying AD onset.

PMID- 29376867
TI  - Antemortem-Postmortem Correlation of Florbetapir (18F) PET Amyloid Imaging with
      Quantitative Biochemical Measures of Abeta42 but not Abeta40.
AB  - Amyloid imaging demonstrates the in vivo presence of amyloid-beta (Abeta)
      deposits in the aging human brain but it is still unknown which structural forms
      and modifications of Abeta are detected. In Alzheimer's disease, most amyloid
      deposits are predominantly composed of Abeta ending at amino acid residues Val40
      or Ala42. It has been reported that Abeta40 is largely restricted to neuritic
      plaques while Abeta42 may be deposited in amyloid plaques of all types, and is
      often the sole component of diffuse plaques. The distinction is important as it
      is mainly the neuritic plaques that correlate with cognitive impairment while
      diffuse plaques may be the initial type of Abeta deposited. Whether PET amyloid
      ligands such as florbetapir-18F (Amyvid) are partially or wholly selective for
      brain deposits of Abeta40 or Abeta42 is currently unknown. We compared antemortem
      florbetapir PET cortical/cerebellar signal intensity (SUVr) of 55 subjects with
      postmortem biochemical (ELISA) measurements employing specific antibodies against
      Abeta40 and Abeta42. Spearman's univariable correlations were significant for
      both Abeta40 and Abeta42, but were much stronger for Abeta42. Multiple linear
      regression showed significance only for Abeta42. These results suggest that
      florbetapir binds only weakly, if at all, to Abeta40. This may be in part due to
      the higher likelihood for Abeta42 to be present in a beta-pleated sheet tertiary
      structure, or to differences between Abeta40 and Abeta42 in beta-pleated sheet
      tertiary or quaternary structure.

PMID- 29376857
TI  - The Relevance of Iron in the Pathogenesis of Multiple System Atrophy: A
      Viewpoint.
AB  - Iron is essential for cellular development and maintenance of multiple
      physiological processes in the central nervous system. The disturbance of its
      homeostasis leads to abnormal iron deposition in the brain and causes
      neurotoxicity via generation of free radicals and oxidative stress. Iron toxicity
      has been established in the pathogenesis of Parkinson's disease; however, its
      contribution to multiple system atrophy (MSA) remains elusive. MSA is
      characterized by cytoplasmic inclusions of misfolded alpha-synuclein (alpha-SYN)
      in oligodendrocytes referred to as glial cytoplasmic inclusions (GCIs).
      Remarkably, the oligodendrocytes possess high amounts of iron, which together
      with GCI pathology make a contribution toward MSA pathogenesis likely. Consistent
      with this observation, the GCI density is associated with neurodegeneration in
      central autonomic networks as well as olivopontocerebellar and striatonigral
      pathways. Iron converts native alpha-SYN into a beta-sheet conformation and
      promotes its aggregation either directly or via increasing levels of oxidative
      stress. Interestingly, alpha-SYN possesses ferrireductase activity and alpha-SYN
      expression underlies iron mediated translational control via RNA stem loop
      structures. Despite a correlation between progressive putaminal atrophy and iron
      accumulation as well as clinical decline, it remains unclear whether pathologic
      iron accumulation in MSA is a secondary event in the cascade of neuronal
      degeneration rather than a primary cause. This review summarizes the current
      knowledge of iron in MSA and gives evidence for perturbed iron homeostasis as a
      potential pathogenic factor in MSA-associated neurodegeneration.

PMID- 29376868
TI  - Geographical Distribution and Diversity of Gut Microbial NADH:Ubiquinone
      Oxidoreductase Sequence Associated with Alzheimer's Disease.
AB  - Earlier we reported induction of neurotoxicity and neurodegeneration by
      tryptophan metabolites that link the metabolic alterations to Alzheimer's disease
      (AD). Tryptophan is a product of Shikimate pathway (SP). Human cells lack SP,
      which is found in human gut bacteria exclusively using SP to produce aromatic
      amino acids (AAA). This study is a first attempt toward gene-targeted analysis of
      human gut microbiota in AD fecal samples. The oligonucleotide primers newly
      designed for this work target SP-AAA in environmental bacteria associated with
      human activity. Using polymerase chain reaction (PCR), we found unique gut
      bacterial sequence in most AD patients (18 of 20), albeit rarely in controls (1
      of 13). Cloning and sequencing AD-associated PCR products (ADPP) enables
      identification of Na(+)-transporting NADH: Ubiquinone reductase (NQR) in
      Clostridium sp. The ADPP of unrelated AD patients possess near identical
      sequences. NQR substrate, ubiquinone is a SP product and human neuroprotectant. A
      deficit in ubiquinone has been determined in a number of neuromuscular and
      neurodegenerative disorders. Antibacterial therapy prompted an ADPP reduction in
      an ADPP-positive control person who was later diagnosed with AD-dementia. We
      explored the gut microbiome databases and uncovered a sequence similarity (up to
      97%) between ADPP and some healthy individuals from different geographical
      locations. Importantly, our main finding of the significant difference in the gut
      microbial genotypes between the AD and control human populations is a
      breakthrough.

PMID- 29376869
TI  - Establishing a New Screening System for Mild Cognitive Impairment and Alzheimer's
      Disease with Mental Rotation Tasks that Evaluate Visuospatial Function.
AB  - BACKGROUND: The mental rotation task is well-known for the assessment of
      visuospatial function; however, it has not been used for screening of dementia
      patients. OBJECTIVE: The aim of this study was to create a simple screening test
      for patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) by
      focusing on non-amnestic symptoms. METHODS: Age-matched healthy controls (age
      75.3+/-6.8), patients with MCI (76.5+/-5.5), and AD (78.2+/-5.0) participated in
      this study. They carried out mental rotation tasks targeting geometric graphics
      or alphabetical characters with three rotating angles (0 degrees , 90 degrees ,
      and 180 degrees ) and indicated the correct answer. Response accuracy and
      reaction time were recorded along with their eye movements using an eye tracker.
      To quantify their visual processing strategy, the run count ratio (RC ratio) was
      calculated by dividing the mean number of fixations in incorrect answers by that
      in correct answers. RESULTS: AD patients showed lower accuracy and longer
      reaction time than controls. They also showed a significantly greater number of
      fixation and smaller saccade amplitude than controls, while fixation duration did
      not differ significantly. The RC ratio was higher for AD, followed by MCI and
      control groups. By setting the cut-off value to 0.47 in the 180 degrees  rotating
      angle task, we could differentiate MCI patients from controls with a probability
      of 80.0%. CONCLUSIONS: We established a new screening system for dementia
      patients by evaluating visuospatial function. The RC ratio during a mental
      rotation task is useful for discriminating MCI patients from controls.

PMID- 29376870
TI  - Assay of Plasma Phosphorylated Tau Protein (Threonine 181) and Total Tau Protein
      in Early-Stage Alzheimer's Disease.
AB  - The feasibility of assaying plasma phosphorylated tau protein (threonine 181),
      denoted p-tau181, using immunomagnetic reduction (IMR) is explored. The reagent
      for assaying p-tau181 with IMR was synthesized, and its analytic performances
      were characterized. Seventy-three subjects were recruited. Each participant was
      examined with neuropsychological tests, magnetic resonance imaging, and IMR assay
      for plasma p-tau181. Using commercially available IMR kits, the plasma total tau
      protein (T-tau) of each subject was assayed. The dynamic range for assaying p
      tau181 using IMR was 1.96*10-2 pg/ml to 104 pg/ml. There was no significant
      interference from total tau protein in the assay of p-tau181. The measured
      concentrations of plasma p-tau181 were 2.46+/-1.09 pg/ml for healthy controls,
      4.41+/-1.85 pg/ml for MCI due to AD, and 6.14+/-1.59 pg/ml for very mild AD.
      Meanwhile, the measured concentrations of plasma T-tau were 18.85+/-10.16 pg/ml
      for healthy controls, 32.98+/-10.18 pg/ml for MCI due to AD, and 37.54+/-12.29
      pg/ml for very mild AD. A significant difference in plasma p-tau181 was observed
      between healthy controls and MCI due to AD (p < 0.001) and between MCI due to AD
      and very mild AD (p < 0.001). However, for the plasma T-tau concentration, a
      significant difference existed only between healthy controls and MCI due to AD (p
      < 0.001). This implies that the plasma p-tau181 level is correlated more to AD
      severity than plasma T-tau is. Additionally, p-tau181 was observed as
      approximately 14% of T-tau in human plasma.

PMID- 29376871
TI  - Retinoic Acid Enhances Apolipoprotein E Synthesis in Human Macrophages.
AB  - Apolipoprotein E (ApoE) represents a pivotal target in Alzheimer's disease (AD)
      and is modulated through retinoic acid (RA), an endogenous neuroprotective and
      anti-inflammatory compound. A major source of ApoE are microglia, which are
      pathologically activated in AD. Activated microglia are known to block RA
      signaling. This suggests a vicious cycle between inflammation, RA signaling, and
      ApoE homeostasis in AD pathogenesis. To test this hypothesis, we investigated
      effects of RA and proinflammatory activation on ApoE synthesis in primary human
      macrophage-derived microglial-like cells. Our results indicate that
      proinflammatory activation attenuates ApoE synthesis, an effect blocked by RA.

PMID- 29376872
TI  - Characteristics of Cognitively Normal Mexican-Americans with Cognitive
      Complaints.
AB  - BACKGROUND: Subjective cognitive complaints in cognitively normal adults have
      been linked to later cognitive decline and dementia. Research on the
      characteristics of this group has been conducted on a variety of clinical and
      community-based populations. The current study focuses on the rapidly expanding
      population of Mexican-American elders. OBJECTIVE: The objective of the study is
      the determination of characteristics of cognitively normal Mexican-Americans with
      cognitive complaints. METHODS: Data on 319 cognitively normal participants in a
      large-scale community-based study of elderly Mexican-Americans (HABLE) were
      analyzed comparing those with cognitive complaints with those without on clinical
      characteristics, affective status, neuropsychological functioning, and proteomic
      markers. RESULTS: Those expressing concern about cognitive decline scored lower
      on the MMSE, were more likely to have significantly more affective symptoms,
      higher levels of diabetic markers, poorer performance on attention and executive
      functioning, and a different pattern of inflammatory markers. CONCLUSION:
      Although longitudinal research is needed to determine the impact of these
      differences on later cognition, possible targets for early intervention with
      Mexican-Americans were identified.

PMID- 29376873
TI  - Lentivirus-Mediated HDAC3 Inhibition Attenuates Oxidative Stress in APPswe/PS1dE9
      Mice.
AB  - Amyloid-beta (Abeta) induces a burst of oxidative stress and plays a critical
      role in the pathogenesis of Alzheimer's disease (AD). Our previous results have
      shown that histone deacetylase 3 (HDAC3) inhibition ameliorates spatial memory
      deficits and decreases the Abeta burden in the brains of 9-month-old
      APPswe/PS1dE9 (APP/PS1) mice. In this study, we investigated the role of HDAC3
      inhibition in oxidative stress in vivo and in vitro models of AD. HDAC3 was
      detected mainly in the neurons, and HDAC3 inhibition significantly decreased
      reactive oxygen species generation and improved primary cortical neuron
      viability. In addition, HDAC3 inhibition attenuated spatial memory dysfunction in
      6-month-old APP/PS1 mice, and decreased the apoptotic rate in the hippocampi as
      demonstrated by TUNEL staining. HDAC3 inhibition also reduced markers of lipid
      peroxidation, protein oxidation, and DNA/RNA oxidation in the hippocampi of
      APP/PS1 mice. Moreover, HDAC3 inhibition inactivated the c-Abl/MST1/YAP signaling
      pathway in the hippocampi of APP/PS1 mice. In conclusion, our data show that
      HDAC3 inhibition can attenuate spatial memory deficits and inhibit oxidative
      stress in APP/PS1 mice; these results indicate a potential strategy for AD
      treatment.

PMID- 29376874
TI  - Profiling of Specific Gene Expression Pathways in Peripheral Cells from Prodromal
      Alzheimer's Disease Patients.
AB  - Herein, we performed a gene expression profiling in a cohort of 10 mild cognitive
      impairment (MCI), subdivided, according to the analysis of cerebrospinal fluid
      biomarkers, in prodromal Alzheimer's disease (AD) and non-AD MCI, as compared
      with 27 AD patients and 24 controls, in order to detect early gene expression
      alterations. We observed a significant upregulation of insulin (INS) and INS
      Receptor (INSR) expression levels in AD both prodromal and fully symptomatic, as
      compared with controls, but not in MCI subjects. Our results suggest an early
      dysregulation of INS and INSR in AD pathogenesis and pave the way to a possible
      utility of these transcripts as peripheral biomarkers.

PMID- 29376875
TI  - White Matter Hyperintensity Predicts the Risk of Incident Cognitive Decline in
      Community Dwelling Elderly.
AB  - BACKGROUND: Unlike western countries, data on white matter hyperintensity (WMH)
      in community dwelling elderly in Asian population is very limited. OBJECTIVE: To
      examine the relation between baseline WMH burden and the risk of incident
      cognitive decline in a community-based cohort with Chinese-dwelling elderly.
      METHODS: We prospectively evaluated the incident cognitive decline for 226
      participants in the Shanghai Aging Study. Baseline WMH severity was visually
      rated by the age-related white matter changes (ARWMC) scale based on MRI. Cox
      proportional hazards regression model was used to estimate the relative risk (RR)
      of total ARWMC scale, global ARWMC score, presence of lacune and microbleed, for
      incident cognitive decline by adjusting potential confounders. RESULTS: Forty
      subjects were identified with incident cognitive decline (new onset 34 mild
      cognitive impairment and 6 dementia) during a median duration of 6 years follow
      up. The incidence of cognitive decline was 3.0 (95% confidence interval [CI] 2.2
      4.1) per 100 person-years. Increasing total ARWMC scale [RR1.21 (95% CI 1.06
      1.39), p = 0.004)], confluent WMH [RR3.16 (95% CI 1.50-6.64), p = 0.002), and
      presence of lacunes [RR 2.73 (95% CI 1.21-6.15)] at baseline were independent
      predictors of incident cognitive decline. CONCLUSION: Our study demonstrated that
      confluent WMH may increase the risk of incident cognitive decline by 3 folds in
      community dwelling subjects. Small vessel disease may cause heavy burden of
      cognitive impairment in the elderly in China.

PMID- 29376876
TI  - Endogenous Murine Amyloid-beta Peptide Assembles into Aggregates in the Aged
      C57BL/6J Mouse Suggesting These Animals as a Model to Study Pathogenesis of
      Amyloid-beta Plaque Formation.
AB  - Amyloid-beta peptide (Abeta), paired helical filament-tau (PHF-tau), and alpha
      synuclein are in the focus of neuroscience research because they aggregate in
      brains of patients with Alzheimer's and Parkinson's diseases. For this purpose,
      transgenic mouse models were used containing the human genes for
      AbetaPP/presenilin/tau or alpha-synuclein with the most frequent mutations. This
      is not ideal because most patients develop sporadic forms of the diseases with no
      causative single gene defect and furthermore the aggregation of human proteins in
      man is not necessarily the same in rodents. We hypothesized that for such cases
      the aged mouse could be an alternative model and analyzed the distribution of
      endogenous Abeta, PHF-tau, and alpha-synuclein in mouse brains at different ages.
      Whereas Abeta was below detectable levels at birth, it was present at high levels
      in the 15-month-old mouse. Abeta was found in the cytosol and lysosomes of
      neurons of the temporal cortex, cingulate area, pons, and cerebellum as well as
      extracellularly in the periventricular zone. Contrary to Abeta, mouse brain was
      devoid of PHF-tau-positive neurofibrillary tangles. alpha-Synuclein was
      detectable in the newborn mouse with highest levels in the marginal zone of the
      lateral cortex and average levels in the hippocampus, pons, and cerebellum. Brain
      area specific differences in the alpha-synuclein level persisted up to 15 months
      of age, but increased 3-fold in all areas over time. alpha-Synuclein resided in
      the neuropil, but not in intracellular aggregates even in the aged mouse. We
      suggest the aged mouse as a model to study Abeta plaque formation.

PMID- 29376877
TI  - A Natural Benzofuran from the Patagonic Aleurodiscus vitellinus Fungus has Potent
      Neuroprotective Properties on a Cellular Model of Amyloid-beta Peptide Toxicity.
AB  - Alzheimer's disease (AD) is characterized by amyloid plaques that form due to an
      increase in amyloid-beta peptide (Abeta) aggregation. One strategy in the search
      of new treatments for AD focuses on compounds that decrease Abeta accumulation.
      Compounds containing a benzofuran ring have been described to play an important
      role in decreasing Abeta-induced toxicity; however, only synthetic benzofurans
      have been tested thus far. The aim of the present study was to examine the in
      vitro neuroprotective properties of fomannoxin (Fx), a natural benzofuran
      isolated from cultures of the Andean-Patagonian fungi Aleurodiscus vitellinus,
      and evaluate its effect on Abeta peptide. We tested the effect of Fx at a wide
      concentration range (10-11-10-4 M) in PC-12 cells, and found the compound did not
      alter cellular viability. Fx also showed a concentration-dependent effect on the
      Abeta-induced toxicity in PC12 cells, showing viability above 100% at 10-6 M. We
      then measured the effect of Fx (10-7-10-5 M) on the frequency of cytosolic Ca2+
      transients in rat hippocampal neurons at both acute and chronic (24 h) times.
      Acute incubation with Fx increased the frequency of cytosolic Ca2+ transients to
      values around 200%, whereas chronic incubation with Fx increased the frequency of
      Ca2+ transients. Finally, the Abeta-induced decrease in intracellular Ca2+
      transients was prevented when Fx (10-6 M) was co-incubated with Abeta (5*10-6 M).
      The results suggest a potent neuroprotective effect of this naturally occurring
      benzofuran against Abeta peptide toxicity that could be mediated by an
      interference with it binding to plasma membrane, and lead Fx as new chemical
      entity to develop pharmacological tools against Abeta peptide neurotoxicity.

PMID- 29376878
TI  - A Longitudinal Study of Total and Phosphorylated alpha-Synuclein with Other
      Biomarkers in Cerebrospinal Fluid of Alzheimer's Disease and Mild Cognitive
      Impairment.
AB  - Alzheimer's disease (AD) features a dynamic sequence of amyloid deposition,
      neurodegeneration, and cognitive impairment. A significant fraction of AD brains
      also displays Lewy body pathology, suggesting that addition of classically
      Parkinson's disease-related proteins to the AD biomarker panel may be of value.
      To determine whether addition of cerebrospinal fluid (CSF) total alpha-synuclein
      and its form phosphorylated at S129 (pS129) to the AD biomarker panel [Amyloid
      beta1-42 (Abeta42), tau, and phosphorylated tau (p-tau181)] improves its
      performance, we examined CSF samples collected longitudinally up to 7 years as
      part of the Alzheimer's Disease Neuroimaging Initiative. From 87 AD, 177 mild
      cognitive impairment (MCI), and 104 age-matched healthy controls, 792 baseline
      and longitudinal CSF samples were tested for total alpha-synuclein, pS129,
      Abeta42, tau, and p-tau181. pS129, but not total alpha-synuclein, was weakly
      associated with diagnosis at baseline when t-tau/Abeta42 was included in the
      statistical model (beta= 0.0026, p = 0.041, 95% CI [(0.0001)-(0.005)]). CSF alpha
      synuclein predicted Alzheimer's Disease Assessment Scale-Cognitive (beta= -0.59,
      p = 0.0015, 95% CI [(-0.96)-(-0.23)]), memory (beta= 0.4, p = 0.00025, 95% CI
      [(0.16)-(0.59)]), and executive (0.62,<0.0001, 95% CI [(0.31)-(0.93)]) function
      composite scores, and progression from MCI to AD (beta= 0.019, p = 0.0011, 95% CI
      [(0.002)-(0.20)]). pS129 was associated with executive function (beta= -2.55, p =
      0.0085, 95% CI [(-4.45)-(-0.66)]). Lower values in the mismatch between alpha
      synuclein and p-tau181 predicted faster cognitive decline (beta= 0.64, p =
      0.0012, 95% CI [(0.48)-(0.84)]). Longitudinal biomarker changes did not differ
      between groups, and may not reflect AD progression. The alpha-synuclein-p-tau181
      Mismatch could better predict longitudinal cognitive changes than classical AD
      markers alone, and its pathological correlates should be investigated further.

PMID- 29376879
TI  - The origin of complex human diversity: Stochastic epistatic modules and the
      intrinsic compatibility between distributional robustness and phenotypic
      changeability
AB  - The continuing prevalence of a highly heritable and hypo-reproductive extreme
      tail of a human neurobehavioral quantitative diversity suggests the reproductive
      majority retains the genetic mechanisms for extremes. From the perspective of
      stochastic epistasis, the effect of an epistatic modifier variant can randomly
      vary in both phenotypic value and effect direction among carriers depending on
      the genetic identity and the modifier carriers are ubiquitous in the population.
      The neutrality of the mean genetic effect in carriers ensures the survival of the
      variant under selection pressures. Functionally or metabolically related modifier
      variants make an epistatic network module and dozens of modules may be involved
      in the phenotype. To assess the significance of stochastic epistasis, a
      simplified module-based model was simulated. The individual repertoire of the
      modifier variants in a module also contributes in genetic identity, which
      determines the genetic contribution of each carrier modifier. Because the entire
      contribution of a module to phenotypic outcome is unpredictable in the model, the
      module effect represents the total contribution of related modifiers as a
      stochastic unit in simulations. As a result, the intrinsic compatibility between
      distributional robustness and quantitative changeability could mathematically be
      simulated using the model. The artificial normal distribution shape in large
      sized simulations was preserved in each generation even if the lowest fitness
      tail was non-reproductive. The robustness of normality across generations is
      analogous to the real situation of complex human diversity, including
      neurodevelopmental conditions. The repeated regeneration of a non-reproductive
      extreme tail may be essential for survival and change of the reproductive
      majority, implying extremes for others. Further simulation to illustrate how the
      fitness of extreme individuals can be low across generations may be necessary to
      increase the plausibility of this stochastic epistasis model.

PMID- 29376881
TI  - Modeling the interaction of navigational systems in a reward-based virtual
      navigation task.
AB  - Existence of allocentric and egocentric systems for human navigation, mediating
      spatial, and response learning, respectively, has so far been discussed. It is
      controversial whether navigational strategies and their underlying learning
      systems and, accordingly, the activation of their associated brain areas are
      independent/parallel or whether they functionally/causally interact in a
      competitive or in a cooperative manner to solve navigational tasks. The insights
      provided by neural networks involved in reward-based navigation attributed to
      individual involvement or interactions of learning systems have been surveyed.
      This paper characterizes the interactions of neural networks by constructing
      generative neural models and investigating their functional and effective
      connectivity patterns. A single-subject computer-based virtual reality
      environment was constructed to simulate a navigation task within a naturalistic
      large-scale space wherein participants were rewarded for using either a place,
      response, or mixed strategy at different navigational stages. First, functional
      analyses were undertaken to evaluate neural activities via mapping brain
      activation and making statistical inference. Effects of interest, spatial and
      response learning/retrieval, and their competition and cooperation were
      investigated. The optimal generative model was then estimated using dynamic
      casual modeling to quantify effective connectivities within the network. This
      analysis revealed how experimental conditions supported competition and
      cooperation strategies and how they modulated the underlying network. Results
      suggest that when navigational strategies cooperated, there were statistically
      significant, functional, and effective connectivities between hippocampus and
      striatum. However, when the strategies competed, effective connections were not
      established among these regions. Instead, connections between
      hippocampus/striatum and prefrontal cortex were strengthened. It can be inferred
      that a type of dynamical reconfiguration occurs within a network responsible for
      navigation when strategies interact either cooperatively or competitively. This
      supports adaptive causal organization of the brain when it is engaged with goal
      directed behavior.

PMID- 29376880
TI  - The role of rosemary extract in degeneration of hippocampal neurons induced by
      kainic acid in the rat: A behavioral and histochemical approach.
AB  - Systemic Kainic Acid (KA) administration has been used to induce experimental
      temporal lobe epilepsy in rats. The aim of this study was to evaluate the
      neuroprotective effect of rosemary extract (RE, 40% Carnosic acid) against KA
      induced neurotoxicity in hippocampus and impaired learning and memory. Animals
      received a single dose of KA (9.5 mg/kg) intraperitoneally (i.p.) (KA group) and
      were observed for 2 h and were scored from 0 (for normal, no convulsion) to 5
      (for continuous generalized limbic seizures). RE (100 mg/kg, orally) was
      administered daily for 23 days, starting a week before KA injection (KA+RE
      group). Neuronal degeneration in hippocampus was demonstrated by using Fluoro
      Jade B immunofluorescence. The number of pyramidal cells in hippocampus was
      evaluated by Nissl staining. Also, the Morris Water Maze and Shuttle box have
      been used to assess spatial memory and passive avoidance learning, respectively.
      Our results revealed that, after treatment with RE, neuronal loss in CA1
      decreased significantly in the animals in KA+RE group. The Morris water
      navigation task results revealed that spatial memory impairment decreased in the
      animals in KA+RE group. Furthermore, results in Shuttle box test showed that
      passive avoidance learning impairment significantly, upgraded in the animals in
      KA+RE group. These results suggest that RE may improve the spatial and working
      memory deficits and also neuronal degeneration induced by toxicity of KA in the
      rat hippocampus, due to its antioxidant activities.

PMID- 29376882
TI  - Relative wave energy-based adaptive neuro-fuzzy inference system for estimation
      of the depth of anaesthesia.
AB  - The advancement in medical research and intelligent modeling techniques has lead
      to the developments in anaesthesia management. The present study is targeted to
      estimate the depth of anaesthesia using cognitive signal processing and
      intelligent modeling techniques. The neurophysiological signal that reflects
      cognitive state of anaesthetic drugs is the electroencephalogram signal. The
      information available on electroencephalogram signals during anaesthesia are
      drawn by extracting relative wave energy features from the anaesthetic
      electroencephalogram signals. Discrete wavelet transform is used to decomposes
      the electroencephalogram signals into four levels and then relative wave energy
      is computed from approximate and detail coefficients of sub-band signals.
      Relative wave energy is extracted to find out the degree of importance of
      different electroencephalogram frequency bands associated with different
      anaesthetic phases awake, induction, maintenance and recovery. The Kruskal-Wallis
      statistical test is applied on the relative wave energy features to check the
      discriminating capability of relative wave energy features as awake, light
      anaesthesia, moderate anaesthesia and deep anaesthesia. A novel depth of
      anaesthesia index is generated by implementing a Adaptive neuro-fuzzy inference
      system based fuzzy c-means clustering algorithm which uses relative wave energy
      features as inputs. Finally, the generated depth of anaesthesia index is compared
      with a commercially available depth of anaesthesia monitor Bispectral index.

PMID- 29376883
TI  - How mental fatigue affects the neural sources of P300 component
AB  - Existence of allocentric and egocentric systems for human navigation, mediating
      spatial, and response learning, respectively, has so far been discussed. It is
      controversial whether navigational strategies and their underlying learning
      systems and, accordingly, the activation of their associated brain areas are
      independent/parallel or whether they functionally/causally interact in a
      competitive or in a cooperative manner to solve navigational tasks. The insights
      provided by neural networks involved in reward-based navigation attributed to
      individual involvement or interactions of learning systems have been surveyed.
      This paper characterizes the interactions of neural networks by constructing
      generative neural models and investigating their functional and effective
      connectivity patterns. A single-subject computer-based virtual reality
      environment was constructed to simulate a navigation task within a naturalistic
      large-scale space wherein participants were rewarded for using either a place,
      response, or mixed strategy at different navigational stages. First, functional
      analyses were undertaken to evaluate neural activities via mapping brain
      activation and making statistical inference. Effects of interest, spatial and
      response learning/retrieval, and their competition and cooperation were
      investigated. The optimal generative model was then estimated using dynamic
      casual modeling to quantify effective connectivities within the network. This
      analysis revealed how experimental conditions supported competition and
      cooperation strategies and how they modulated the underlying network. Results
      suggest that when navigational strategies cooperated, there were statistically
      significant, functional, and effective connectivities between hippocampus and
      striatum. However, when the strategies competed, effective connections were not
      established among these regions. Instead, connections between
      hippocampus/striatum and prefrontal cortex were strengthened. It can be inferred
      that a type of dynamical reconfiguration occurs within a network responsible for
      navigation when strategies interact either cooperatively or competitively. This
      supports adaptive causal organization of the brain when it is engaged with goal
      directed behavior.

PMID- 29376884
TI  - Investigating visual effects of a disgust nocebo with fMRI.
AB  - There is growing evidence that placebos are able to influence visual perception.
      A previous functional magnetic resonance imaging study on the processing of
      disgust images demonstrated that a ''disgust placebo'' (inert pill administered
      with the verbal suggestion of an anti-nausea medication) reduced visual cortex
      activity and connectivity. In the present functional magnetic resonance imaging
      investigation, visual effects corresponding to a ''disgust nocebo'' (an odorless
      substance introduced as an aversive smell that enhances disgust feelings) were
      examined. Data from 29 females were reanalyzed. They viewed disgusting, fear
      eliciting, and neutral images once with and once without the nocebo. In the
      nocebo condition with disgusting images disgust experienced that significantly
      increased fusiform gyrus activation, which also showed enhanced coupling with the
      amygdala and several (extra)striate cortex regions. The nocebo changed the
      affective value and motivational relevance of the stimuli as well the perception
      of basic visual features. These findings demonstrate that nocebo-related
      expectations can have a strong influence on the experience of sensory input.

PMID- 29376885
TI  - Application of a brain-computer interface for person authentication using EEG
      responses to photo stimuli.
AB  - In this paper, a personal authentication system that can effectively identify
      individuals by generating unique electroencephalogram signal features in response
      to self-face and non-self-face photos is presented. To achieve performance
      stability, a sequence of self-face photographs including first-occurrence
      position and non-first-occurrence position are taken into account in the serial
      occurrence of visual stimuli. Additionally, a Fisher linear classification method
      and event-related potential technique for feature analysis is adapted to yield
      remarkably better outcomes than those obtained by most existing

PMID- 29376886
TI  - Scalp acupuncture plus low-frequency rTMS promotes repair of brain white matter
      tracts in stroke patients: A DTI study.
AB  - To study the clinical effects of scalp acupuncture plus low frequency rTMS in
      hemiplegic stroke patients. A total of 28 hemiplegic stroke patients were
      recruited and randomly assigned to the experimental group (scalp acupuncture low
      frequency rTMS routine rehabilitation treatment) or the control group (scalp
      acupuncture routine rehabilitation treatment). All patients received a diffusion
      tensor imaging examination on the day of admission and on the fourteenth day.
      Compared with pre-treatment, the upper limb motor function score and ability of
      daily life score increased significantly in the two groups, and motor function
      improvement was much greater in the experimental group. Fractional anisotropy
      values significantly increased in white matter tracts, such as the corticospinal
      tract, forceps minor, superior longitudinal fasciculus and uncinate fasciculus in
      the two groups. Compared with pretreatment, the fractional anisotropy values
      increased and mean diffusion values decreased synchronously in the forceps minor,
      left inferior fronto-occipital fasciculus, left inferior longitudinal fasciculus,
      left superior longitudinal fasciculus and left uncinate fasciculus in the
      experimental group. Before and after treatment, there were no significant
      differences in the changes of fractional anisotropy values between the two
      groups, but the changes of the mean diffusion values in the experimental group
      were much greater than those in the control group in the left superior
      longitudinal fasciculus and the left uncinate fasciculus (p<0.05). Moreover, the
      increased fractional anisotropy values in the forceps minor in the experimental
      group were significantly positively correlated with the increased Fugl-Meyer
      assessment score. Our study concluded that based on routine rehabilitation
      treatment, scalp acupuncture plus low frequency rTMS can promote white matter
      tracts repair better than scalp acupuncture alone; the motor function improvement
      of the hemiplegic upper limb may be closely related to the rehabilitation of the
      forceps minor; the combination of scalp acupuncture and low frequency rTMS is
      expected to provide a more optimal rehabilitation protocol for stroke hemiplegic
      patients.

PMID- 29376887
TI  - Hypothalamic loss of Snord116 recapitulates the hyperphagia of Prader-Willi
      syndrome.
AB  - Profound hyperphagia is a major disabling feature of Prader-Willi syndrome (PWS).
      Characterization of the mechanisms that underlie PWS-associated hyperphagia has
      been slowed by the paucity of animal models with increased food intake or
      obesity. Mice with a microdeletion encompassing the Snord116 cluster of noncoding
      RNAs encoded within the Prader-Willi minimal deletion critical region have
      previously been reported to show growth retardation and hyperphagia. Here,
      consistent with previous reports, we observed growth retardation in Snord116+/-P
      mice with a congenital paternal Snord116 deletion. However, these mice neither
      displayed increased food intake nor had reduced hypothalamic expression of the
      proprotein convertase 1 gene PCSK1 or its upstream regulator NHLH2, which have
      recently been suggested to be key mediators of PWS pathogenesis. Specifically, we
      disrupted Snord116 expression in the mediobasal hypothalamus in Snord116fl mice
      via bilateral stereotaxic injections of a Cre-expressing adeno-associated virus
      (AAV). While the Cre-injected mice had no change in measured energy expenditure,
      they became hyperphagic between 9 and 10 weeks after injection, with a subset of
      animals developing marked obesity. In conclusion, we show that selective
      disruption of Snord116 expression in the mediobasal hypothalamus models the
      hyperphagia of PWS.

PMID- 29376888
TI  - Microglia are required for protection against lethal coronavirus encephalitis in
      mice.
AB  - Recent findings have highlighted the role of microglia in orchestrating normal
      development and refining neural network connectivity in the healthy CNS.
      Microglia are not only vital cells in maintaining CNS homeostasis, but also
      respond to injury, infection, and disease by undergoing proliferation and changes
      in transcription and morphology. A better understanding of the specific role of
      microglia in responding to viral infection is complicated by the presence of
      nonmicroglial myeloid cells with potentially overlapping function in the healthy
      brain and by the rapid infiltration of hematopoietic myeloid cells into the brain
      in diseased states. Here, we used an inhibitor of colony-stimulating factor 1
      receptor (CSF1R) that depletes microglia to examine the specific roles of
      microglia in response to infection with the mouse hepatitis virus (MHV), a
      neurotropic coronavirus. Our results show that microglia were required during the
      early days after infection to limit MHV replication and subsequent morbidity and
      lethality. Additionally, microglia depletion resulted in ineffective T cell
      responses. These results reveal nonredundant, critical roles for microglia in the
      early innate and virus-specific T cell responses and for subsequent host
      protection from viral encephalitis.

PMID- 29376890
TI  - Newly found arsons ignite the fire of gut GVHD.
AB  - Acute graft-versus-host disease (GVHD) in the gut is common following
      hematopoetic cell transplantation (HCT) and is associated with high mortality.
      However, it remains unclear whether Th1 or Th17 CD4+ T cells can initiate acute
      gut GVHD. In this issue of the JCI, Ullrich and colleagues identified a subset of
      CD4+ T cells that express high levels of IL-7Ralpha and granulocyte-macrophage
      CSF (IL-7RalphahiGM-CSF+) cells that are involved in the induction of acute gut
      GVHD in murine models. The IL-7RalphahiGM-CSF+ effector memory cells were BATF
      dependent, RORgammat independent, produced large amounts of GM-CSF and IFN-gamma,
      and released little IL-17. CD4+IL-7RalphahiGM-CSF+ cells were not classical Th17
      cells but had more of a Th1-like phenotype, despite their dependence on BATF.
      This work suggests that targeting the IL-7R/BATF/GM-CSF axis has therapeutic
      potential for treating acute gut GVHD.

PMID- 29376889
TI  - BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host
      disease.
AB  - Acute graft-versus-host disease (GVHD) represents a severe, T cell-driven
      inflammatory complication following allogeneic hematopoietic cell transplantation
      (allo-HCT). GVHD often affects the intestine and is associated with a poor
      prognosis. Although frequently detectable, proinflammatory mechanisms exerted by
      intestinal tissue-infiltrating Th cell subsets remain to be fully elucidated.
      Here, we show that the Th17-defining transcription factor basic leucine zipper
      transcription factor ATF-like (BATF) was strongly regulated across human and
      mouse intestinal GVHD tissues. Studies in complete MHC-mismatched and minor
      histocompatibility-mismatched (miHA-mismatched) GVHD models revealed that BATF
      expressing T cells were functionally indispensable for intestinal GVHD
      manifestation. Mechanistically, BATF controlled the formation of colon
      infiltrating, IL-7 receptor-positive (IL-7R+), granulocyte-macrophage colony
      stimulating factor-positive (GM-CSF+), donor T effector memory (Tem) cells. This
      T cell subset was sufficient to promote intestinal GVHD, while its occurrence was
      largely dependent on T cell-intrinsic BATF expression, required IL-7-IL-7R
      interaction, and was enhanced by GM-CSF. Thus, this study identifies BATF
      dependent pathogenic GM-CSF+ effector T cells as critical promoters of intestinal
      inflammation in GVHD and hence putatively provides mechanistic insight into
      inflammatory processes previously assumed to be selectively Th17 driven.

PMID- 29376891
TI  - Hypothalamic loss of Snord116 and Prader-Willi syndrome hyperphagia: the buck
      stops here?
AB  - Hyperphagia and obesity are the best-known manifestations of Prader-Willi
      syndrome (PWS) and are responsible for most of the overall morbidity and
      mortality associated with the disease. Yet these PWS symptoms remain poorly
      understood and without effective pharmacologic therapies. Mouse models attempting
      to recapitulate both the genetic alterations and marked hyperphagia plus obesity
      of PWS have been enigmatic, leading to skepticism about the use of mouse models
      to investigate PWS. In this issue of the JCI, Polex-Wolf and colleagues challenge
      the skeptics by successfully inducing hyperphagia following bilateral mediobasal
      hypothalamic deletion of the Snord116 gene from adult mice. Obesity also
      resulted, although only in a subset of mice. While this approach represents an
      exciting advance, highlighting a pathologic effect of loss of mediobasal
      hypothalamic Snord116 expression on the development of PWS's hallmark symptoms,
      the variability in the body-weight and body composition responses to this site
      selective gene deletion raises several questions.

PMID- 29376893
TI  - Use of Ocular Hypotensive Medications in Portugal: PEM Study: A Cross-sectional
      Nationwide Analysis: Erratum.

PMID- 29376894
TI  - Welcome Message from the Editor-in-Chief.
AB  - Fungi are one of the most important and diverse groups of organisms on the
      planet, having a dual impact on humanity. They adversely impact human and animal
      health and can be a scourge to agriculture, while in turn serving as a beneficial
      source for foods and beverages, new medications, and biocontrol. There are
      approximately 1.5 million different species of fungi on Earth, which largely
      reside in soil and plant. They are also readily found on human skin and within
      the gastrointestinal and genitourinary tract, yet only about 300 species are
      known to make people sick [1,2]. Fungi are bountiful in the environment and we
      encounter them everyday, usually in the form of freely dispersed spores and
      hyphal fragments that we breath-in. Typically, encounters with fungi are
      harmless, as the human immune systems is well poised to handle such interactions.
      However, some fungal species pose significant health risks, such as endemic
      mycoses or those producing toxins like mycotoxins. Most importantly, immune
      dysfunction can lead to serious life-threatening diseases or severe fungal
      induced allergic diseases such as asthma or other chronic conditions [3]. In
      fact, most invasive fungal diseases are associated with changes in the host such
      as immunosuppression, antibiotic-mediated disruption of microflora, or other
      immunosuppressing conditions resulting from HIV/AIDS and hematologic malignancies
      [3,4]. Such diseases require therapy with antifungal agents. Yet, there are only
      limited classes available to treat invasive fungal infection, and emerging drug
      resistance further restricts treatment options. In some cases, agents used to
      control agriculturally important moulds are the same class as those used to treat
      humans, and de novo resistance can emerge from the environment [5]. Fungi are not
      always easy to detect and cryptic chronic infections in the form of unculturable
      organisms can confound diagnosis [6]. [...].

PMID- 29376892
TI  - Factor XII and uPAR upregulate neutrophil functions to influence wound healing.
AB  - Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil
      migration, but the mechanisms remain uncharacterized. Here, we examine how FXII
      contributes to the inflammatory response. In 2 models of sterile inflammation,
      FXII-deficient mice (F12-/-) had fewer neutrophils recruited than WT mice. We
      discovered that neutrophils produced a pool of FXII that is functionally distinct
      from hepatic-derived FXII and contributes to neutrophil trafficking at sites of
      inflammation. FXII signals in neutrophils through urokinase plasminogen activator
      receptor-mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474).
      Downstream of pAkt2S474, FXII stimulation of neutrophils upregulated surface
      expression of alphaMbeta2 integrin, increased intracellular calcium, and promoted
      extracellular DNA release. The sum of these activities contributed to neutrophil
      cell adhesion, migration, and release of neutrophil extracellular traps in a
      process called NETosis. Decreased neutrophil signaling in F12-/- mice resulted in
      less inflammation and faster wound healing. Targeting hepatic F12 with siRNA did
      not affect neutrophil migration, whereas WT BM transplanted into F12-/- hosts was
      sufficient to correct the neutrophil migration defect in F12-/- mice and restore
      wound inflammation. Importantly, these activities were a zymogen FXII function
      and independent of FXIIa and contact activation, highlighting that FXII has a
      sophisticated role in vivo that has not been previously appreciated.

PMID- 29376895
TI  - Cutaneous Protothecosis in a Patient with Chronic Lymphocytic Leukemia: A Case
      Report and Literature Review.
AB  - Protothecosis is a rare infection, which has the potential to cause severe
      disease in patients with underlying immunosuppression. We describe a case of an
      elderly female with chronic lymphocytic leukemia (CLL), as well as other risk
      factors, who presented with pustular and erythematous plaques, initially presumed
      to be leukemia cutis. A biopsy with special stains revealed the lesions to be
      cutaneous protothecosis, thus presenting a most unusual concurrence of disease
      entities. The literature to date on this rare infection will be reviewed.

PMID- 29376896
TI  - Antifungal Treatment for Pityriasis Versicolor.
AB  - BACKGROUND: Pityriasis versicolor (PV), also known as tinea versicolor, is caused
      by Malassezia species. This condition is one of the most common superficial
      fungal infections worldwide, particularly in tropical climates. PV is difficult
      to cure and the chances for relapse or recurrent infections are high due to the
      presence of Malassezia in the normal skin flora. This review focuses on the
      clinical evidence supporting the efficacy of antifungal treatment for PV. METHOD:
      A systematic review of literature from the PubMed database was conducted up to 30
      September 2014. The search criteria were "(pityriasis versicolor OR tinea
      versicolor) AND treatment", with full text available and English language
      required. CONCLUSIONS: Topical antifungal medications are the first-line
      treatment for PV, including zinc pyrithione, ketoconazole, and terbinafine. In
      cases of severe or recalcitrant PV, the oral antifungal medications itraconazole
      and fluconazole may be more appropriate, with pramiconazole a possible future
      option. Oral terbinafine is not effective in treating PV and oral ketoconazole
      should no longer be prescribed. Maintenance, or prophylactic, therapy may be
      useful in preventing recurrent infection; however, at this time, there is limited
      research evaluating the efficacy of prophylactic antifungal treatment.

PMID- 29376897
TI  - Onychomycosis: A Review.
AB  - Onychomycosis is the most common nail infective disorder. It is caused mainly by
      anthropophilic dermatophytes, in particular by Trichophyton rubrum and T.
      mentagrophytes var. interdigitale. Yeasts, like Candida albicans and C.
      parapsilosis, and molds, like Aspergillus spp., represent the second cause of
      onychomycosis. The clinical suspect of onychomycosis should be confirmed my
      mycology. Onychoscopy is a new method that can help the physician, as in
      onychomycosis, it shows a typical fringed proximal margin. Treatment is chosen
      depending on the modality of nail invasion, fungus species and the number of
      affected nails. Oral treatments are often limited by drug interactions, while
      topical antifungal lacquers have less efficacy. A combination of both oral and
      systemic treatment is often the best choice.

PMID- 29376898
TI  - Laser Therapy for Onychomycosis: Fact or Fiction?
AB  - Onychomycosis is a common fungal infection, afflicting some 10% of the adult
      population in industrialized countries. Aside from cosmetic concerns,
      onychomycosis can be the cause of toe and foot pain, as well as the underlying
      etiology for serious secondary bacterial infections and traumatic ulcerations. In
      select populations, such as diabetics, the latter conditions may even result in
      loss of all or part of the lower extremity. Thus, a simple, cost-effective and
      safe treatment for onychomycosis is highly desirable. Although both topical and
      oral systemic antifungal agents are available for this purpose, they are not
      always effective, carry some medical risks, are associated with potentially
      significant drug-drug interactions, and may be unacceptable to patient and
      healthcare provider alike. Physical modalities, such as laser therapy, therefore
      appear appealing. The question is whether laser treatment is sufficiently
      efficacious and safe to warrant the current high cost per treatment. The readily
      available literature on this controversy will be reviewed herein.

PMID- 29376899
TI  - Host-Specialist Dominated Ectomycorrhizal Communities of Pinus cembra are not
      Affected by Temperature Manipulation.
AB  - Ectomycorrhizae (EM) are important for the survival of seedlings and trees, but
      how they will react to global warming or changes in soil fertility is still in
      question. We tested the effect of soil temperature manipulation and nitrogen
      fertilization on EM communities in a high-altitude Pinus cembra afforestation.
      The trees had been inoculated in the 1960s in a nursery with a mixture of Suillus
      placidus, S. plorans and S. sibircus. Sampling was performed during the third
      year of temperature manipulation in June and October 2013. Root tips were
      counted, sorted into morphotypes, and sequenced. Fungal biomass was measured as
      ergosterol and hyphal length. The EM potential of the soil was assessed with
      internal transcribed spacers (ITS) clone libraries from in-growth mesh bags (MB).
      Temperature manipulation of +/- 1  degrees C had no effect on the EM community. A
      total of 33 operational taxonomic units (OTUs) were identified, 20 from the
      roots, 13 from MB. The inoculated Suillus spp. colonized 82% of the root tips,
      thus demonstrating that the inoculation was sustainable. Nitrogen fertilization
      had no impact on the EM community, but promoted depletion in soil organic matter,
      and caused a reduction in soil fungal biomass.

PMID- 29376900
TI  - Analyses of Sporocarps, Morphotyped Ectomycorrhizae, Environmental ITS and LSU
      Sequences Identify Common Genera that Occur at a Periglacial Site.
AB  - Periglacial substrates exposed by retreating glaciers represent extreme and
      sensitive environments defined by a variety of abiotic stressors that challenge
      organismal establishment and survival. The simple communities often residing at
      these sites enable their analyses in depth. We utilized existing data and mined
      published sporocarp, morphotyped ectomycorrhizae (ECM), as well as environmental
      sequence data of internal transcribed spacer (ITS) and large subunit (LSU)
      regions of the ribosomal RNA gene to identify taxa that occur at a glacier
      forefront in the North Cascades Mountains in Washington State in the USA. The
      discrete data types consistently identified several common and widely distributed
      genera, perhaps best exemplified by Inocybe and Laccaria. Although we expected
      low diversity and richness, our environmental sequence data included 37 ITS and
      26 LSU operational taxonomic units (OTUs) that likely form ECM. While
      environmental surveys of metabarcode markers detected large numbers of targeted
      ECM taxa, both the fruiting body and the morphotype datasets included genera that
      were undetected in either of the metabarcode datasets. These included hypogeous
      (Hymenogaster) and epigeous (Lactarius) taxa, some of which may produce large
      sporocarps but may possess small and/or spatially patchy genets. We highlight the
      importance of combining various data types to provide a comprehensive view of a
      fungal community, even in an environment assumed to host communities of low
      species richness and diversity.

PMID- 29376901
TI  - Histoplasmosis and Blastomycosis in Solid Organ Transplant Recipients.
AB  - Histoplasmosis and blastomycosis are geographically restricted dimorphic fungi
      that cause infection after the conidia produced in the mold phase are inhaled
      into the lungs. In the lungs, at 37  degrees C, these organisms undergo
      transformation into the yeast phase. In transplant recipients, infection can
      occur by exposure to the mold in the environment, by reactivation of infection
      that had occurred previously and had been controlled by the host until
      immunosuppressive medications were given post-transplantation, and finally by
      transmission from the donor organ in the case of histoplasmosis. In transplant
      recipients, disseminated infection is common, and pulmonary infection is more
      likely to be severe than in a non-immunosuppressed person. Diagnosis has been
      improved, allowing earlier treatment, with the use of rapid antigen tests
      performed on serum and urine. Initial treatment, for all but the mildest cases of
      acute pulmonary histoplasmosis, should be with a lipid formulation of
      amphotericin B. After clinical improvement has occurred, step-down therapy with
      itraconazole is recommended for a total of 12 months for most transplant
      recipients, but some patients will require long-term suppressive therapy to
      prevent relapse of disease.

PMID- 29376902
TI  - Efinaconazole Topical Solution, 10%: Factors Contributing to Onychomycosis
      Success.
AB  - To provide an adequate therapeutic effect against onychomycosis, it has been
      suggested that topical drugs should have two properties: drug permeability
      through the nail plate and into the nail bed, and retention of their antifungal
      activity in the disease-affected areas. Only recently has the importance of other
      delivery routes (such as subungual) been discussed. Efinaconazole has been shown
      to have a more potent antifungal activity in vitro than the most commonly used
      onychomycosis treatments. The low keratin affinity of efinaconazole contributes
      to its effective delivery through the nail plate and retention of its antifungal
      activity. Its unique low surface tension formulation provides good wetting
      properties affording drug delivery both through and under the nail. High
      antifungal drug concentrations have been demonstrated in the nail of
      onychomycosis patients, and effectiveness of efinaconazole topical solution, 10%
      confirmed in two large well-controlled multicenter Phase 3 clinical studies in
      patients with mild-to-moderate disease.

PMID- 29376903
TI  - Cryptococcus: Shedding New Light on an Inveterate Yeast.
AB  - Cryptococcus has emerged as a significant pathogen in immunocompromised patients.
      While the diagnostic testing and the antifungal treatment of cryptococcal
      infections have become firmly established in clinical practice, new developments
      and areas of ambiguity merit further consideration. These include the potential
      for donor transmission of Cryptococcus; cirrhosis-associated cryptococcosis,
      particularly during transplant candidacy; the utility of serum cryptococcal
      antigen testing of asymptomatic individuals in high-prevalence, poor-resource
      areas; pathogenesis and treatment of the immune reconstitution syndrome,
      specifically in relation to antiretroviral therapy and immunosuppressive
      medications; and new challenges posed by the emerging species of Cryptococcus
      gatti. In this article, we summarize the literature pertaining to these topics,
      focusing on recent progress.

PMID- 29376904
TI  - The Immunologic Response to Trichophyton Rubrum in Lower Extremity Fungal
      Infections.
AB  - Manifestations of Trichophyton rubrum infestations, such as tinea pedis, tinea
      cruris, and tinea corporis, are among the most common human skin diseases seen
      throughout the world. About 80% of patients presenting with acute dermatophytosis
      respond well to topical antifungal treatment. However, the remaining 20% of
      patients progress into a chronic state of dermatophytosis, which is resistant to
      antifungal treatment. Therefore, it is necessary to have a better understanding
      and appreciation for the diverse immune responses to Trichophyton as this is
      critical for the development of therapeutic strategies for those individuals who
      suffer from a chronic manifestation of Trichophyton rubrum (T. rubrum) infection.
      As a result, a comprehensive literature review was conducted to review and
      discuss previous studies that evaluated the human body's defense to T. rubrum
      infections and to understand why and how these fungal infections invade the host
      defense system. Our research revealed that a cell-mediated immune response is
      critical in defending the body against T. rubrum. However, this organism has
      mechanisms that enable it to evade the immune system. Therefore, a more
      successful treatment for chronic T. rubrum infection would involve targeting the
      mechanisms of T. rubrum that diminish the immune response, while restoring the
      cell-mediated immune response.

PMID- 29376905
TI  - Effective Single Photodynamic Treatment of ex Vivo Onychomycosis Using a
      Multifunctional Porphyrin Photosensitizer and Green Light.
AB  - Onychomycosis is predominantly caused by the dermatophytes Trichophyton rubrum,
      Trichophyton mentagrophytes and Trichophyton tonsurans. The main treatment
      obstacle concerns low nail-plate drug permeability. In vitro antifungal
      photodynamic treatment (PDT) and nail penetration enhancing effectiveness have
      been proven for multifunctional photosensitizer 5,10,15-tris(4-N
      methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]
      porphine trichloride (PORTHE). This study investigates single PORTHE green
      laser/LED PDT of varying degrees of ex vivo onychomycoses in a human nail model.
      T. mentagrophytes, T. rubrum, T. tonsurans onychomycoses were ex vivo induced on
      nail pieces at 28  degrees C (normal air) and 37  degrees C (6.4% CO2) during 3
      to 35 days and PDTs applied to the 37  degrees C infections. All dermatophytes
      showed increasingly nail plate invasion at 37  degrees C between 7 and 35 days;
      arthroconidia were observed after 35 days for T. mentagrophytes and T. tonsurans.
      Using 81 J/cm2 (532 nm) 7-day T. mentagrophytes onychomycoses were cured (92%)
      with 80 uM PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and
      35-day onychomycoses (52%-67%) with 24 h PORTHE (40-80 uM)/40% PG treatment (pH
      5). 28 J/cm2 LED light (525 +/- 37 nm) improved cure rates to 72%, 83% and 73%
      for, respectively, T. mentagrophytus, T. rubrum and T. tonsurans 35-day
      onychomycoses and to 100% after double PDT. Data indicate PDT relevance for
      onychomycosis.

PMID- 29376906
TI  - Special Issue: Mycorrhizal Fungi in Sensitive Environments.
AB  - The scope of this special issue is to understand whether and how mycorrhizal
      symbiosis can be included as an agriculture and agroforestry tool that promotes
      more environmentally friendly practices, and whether it promotes the protection
      of sensitive areas. Three papers are included in this special issue, each dealing
      with a different sensitive environment. These papers present fundamental aspects
      that should be taken into account when planning or reporting studies related to
      mycorrhizal fungi in sensitive environments.

PMID- 29376907
TI  - The Dermatologist's Approach to Onychomycosis.
AB  - Onychomycosis is a fungal infection of the toenails or fingernails that can
      involve any component of the nail unit, including the matrix, bed, and plate. It
      is a common disorder that may be a reservoir for infection resulting in
      significant medical problems. Moreover, onychomycosis can have a substantial
      influence on one's quality of life. An understanding of the disorder and updated
      management is important for all health care professionals. Aside from reducing
      quality of life, sequelae of the disease may include pain and disfigurement,
      possibly leading to more serious physical and occupational limitations.
      Dermatologists, Podiatrists, and other clinicians who treat onychomycosis are now
      entering a new era when considering treatment options-topical modalities are
      proving more effective than those of the past. The once sought after concept of
      viable, effective, well-tolerated, and still easy-to-use monotherapy alternatives
      to oral therapy treatments for onychomycosis is now within reach given recent
      study data. In addition, these therapies may also find a role in combination and
      maintenance therapy; in order to treat the entire disease the practitioner needs
      to optimize these topical agents as sustained therapy after initial clearance to
      reduce recurrence or re-infection given the nature of the disease.

PMID- 29376908
TI  - Ectomycorrhizal Fungal Communities and Enzymatic Activities Vary across an
      Ecotone between a Forest and Field.
AB  - Extracellular enzymes degrade macromolecules into soluble substrates and are
      important for nutrient cycling in soils, where microorganisms, such as
      ectomycorrhizal (ECM) fungi, produce these enzymes to obtain nutrients. Ecotones
      between forests and fields represent intriguing arenas for examining the effect
      of the environment on ECM community structure and enzyme activity because tree
      maturity, ECM composition, and environmental variables may all be changing
      simultaneously. We studied the composition and enzymatic activity of ECM
      associated with loblolly pine (Pinus taeda) across an ecotone between a forest
      where P. taeda is established and an old field where P. taeda saplings had been
      growing for <5 years. ECM community and environmental characteristics influenced
      enzyme activity in the field, indicating that controls on enzyme activity may be
      intricately linked to the ECM community, but this was not true in the forest.
      Members of the Russulaceae were associated with increased phenol oxidase activity
      and decreased peroxidase activity in the field. Members of the Atheliaceae were
      particularly susceptible to changes in their abiotic environment, but this did
      not mediate differences in enzyme activity. These results emphasize the complex
      nature of factors that dictate the distribution of ECM and activity of their
      enzymes across a habitat boundary.

PMID- 29376909
TI  - Environmental and Genetic Factors on the Development of Onychomycosis.
AB  - Since the early 20th century, onychomycosis originated with the onset of war, the
      use of occlusive footwear, and the mass migration of people by transportation in
      the United States. Even though onychomycosis has a high prevalence in the US,
      other parts of the world including Canada, West Africa, Southeast Asia, Northern
      Australia, and Europe have been well documented with cases of fungal toenail
      infection in their environments. Trichophyton rubrum (T. rubrum) is the major
      dermatophyte responsible for toenail fungal infection and is typically diagnosed
      in conjunction with tinea pedis, especially in individuals older than 60 years.
      Gender roles, age, cultural habits, shoe gear, sports activities, and genetic
      predisposition all contribute to the different presentation of onychomycosis in
      these areas where organisms like dermatophytes, candida, and molds were isolated
      in a variety of cases. Despite the differences in isolated pathogens, treatment
      outcomes remained consistent. This literature review discusses the influence of
      tinea pedis, genetics, shoe gear, sports, and age on the development of
      onychomycosis.

PMID- 29376911
TI  - Diagnostic Modalities for Invasive Mould Infections among Hematopoietic Stem Cell
      Transplant and Solid Organ Recipients: Performance Characteristics and Practical
      Roles in the Clinic.
AB  - The morbidity and mortality of hematopoietic stem cell and solid organ transplant
      patients with invasive fungal infections (IFIs) remain high despite an increase
      in the number of effective antifungal agents. Early diagnosis leading to timely
      administration of antifungal therapy has been linked to better outcomes.
      Unfortunately, the diagnosis of IFIs remains challenging. The current gold
      standard for diagnosis is a combination of histopathology and culture, for which
      the sensitivity is <50%. Over the past two decades, a plethora of non-culture
      based antigen and molecular assays have been developed and clinically validated.
      In this article, we will review the performance of the current commercially
      available non-cultural diagnostics and discuss their practical roles in the
      clinic.

PMID- 29376910
TI  - Application of Culture-Independent Rapid Diagnostic Tests in the Management of
      Invasive Candidiasis and Cryptococcosis.
AB  - The diagnosis of invasive candidiasis (IC) and cryptococcosis is often
      complicated by slow and insensitive culture-based methods. Such delay results in
      poor outcomes due to the lack of timely therapeutic interventions. Advances in
      serological, biochemical, molecular and proteomic approaches have made a
      favorable impact on this process, improving the timeliness and accuracy of
      diagnosis with resultant improvements in outcome. This paper will serve as an
      overview of recent developments in the diagnostic approaches to infections due to
      these important yeast-fungi.

PMID- 29376912
TI  - Candida glabrata, Friend and Foe.
AB  - Candida glabrata is mostly good, but, at times, it is an opportunistic pathogen.
      Previously known as Torulopsis glabrata, it enjoyed a good reputation and was
      even present in starter cultures. Its haploid genome and lack of mating made it
      an attractive challenge for yeast genetics studies. However, more recently it has
      become better known due to its character as an emerging cause of candidiasis, and
      for its resistance to multidrugs that are employed for candidiasis treatment.
      While now classified as Candida glabrata, it is still not a good fit and tends to
      stand alone as a very unique yeast. In terms of sequence, it is dissimilar to
      other Candida yeast and most similar to Saccharomyces cerevisiae.

PMID- 29376914
TI  - The Fungus among Us: Cryptococcus neoformans and Cryptococcus gattii Ecological
      Modeling for Colombia.
AB  - The environmental isolation of Cryptococcus spp. is typically a difficult
      undertaking. Collecting samples in the field is costly in terms of travel,
      personnel time and materials. Furthermore, the recovery rate of Cryptococcus spp.
      may be very low, thereby requiring a large number of samples to be taken without
      any guarantee of success. Ecological niche modeling is a tool that has
      traditionally been used to forecast the distribution of plant and animal of
      species for biodiversity and conservation purposes. Here, we use it in a public
      health application to produce risk area maps for cryptococcal disease in
      Colombia. The Genetic Algorithm for Ruleset Production (GARP) was used to create
      models for Cryptococcus neoformans (C. neoformans) and Cryptococcus gattii (C.
      gattii), based on environmental sampling and clinical records data recorded since
      1987. These maps could be used to focus public health messaging related to
      cryptococcal disease, and it enables us to characterize the ecological niche for
      Cryptococcus in Colombia. We found that the OPEN ACCESS J. Fungi 2015, 1 333
      ecological niche for C. gattii in Colombia is quite diverse, establishing itself
      in sub-tropical and temperate ecoregions within the country. This suggests that
      C. gattii is highly adaptive to different ecological conditions in Colombia and
      different regions of the world.

PMID- 29376915
TI  - Role of New Antifungal Agents in the Treatment of Invasive Fungal Infections in
      Transplant Recipients: Isavuconazole and New Posaconazole Formulations.
AB  - Invasive fungal infections are a major cause of morbidity and mortality among
      solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT)
      recipients. Transplant patients are at risk for such invasive fungal infections.
      The most common invasive fungal infections are invasive candidiasis in the SOT
      and invasive aspergillosis in the HSCT. In this article, we will discuss the
      epidemiology of invasive fungal infections in the transplant recipients and
      susceptibility patterns of the fungi associated with these infections.
      Additionally, the pharmacology and clinical efficacy of the new antifungal,
      isavuconazole, and the new posaconazole formulations will be reviewed.
      Isavuconazole is a new extended-spectrum triazole that was recently approved for
      the treatment of invasive aspergillosis and mucormycosis. Advantages of this
      triazole include the availability of a water-soluble intravenous formulation,
      excellent bioavailability of the oral formulation, and predictable
      pharmacokinetics in adults. Posaconazole, a broad-spectrum triazole antifungal
      agent, is approved for the prevention of invasive aspergillosis and candidiasis
      in addition to the treatment of oropharyngeal candidiasis. Posaconazole oral
      suspension solution has shown some limitations in the setting of fasting state
      absorption, elevated gastrointestinal pH, and increased motility. The newly
      approved delayed-release oral tablet and intravenous solution formulations
      provide additional treatment options by reducing interpatient variability and
      providing flexibility in these set of critically ill patients. This review will
      detail these most recent studies.

PMID- 29376913
TI  - Pneumocystis Pneumonia in Solid-Organ Transplant Recipients.
AB  - Pneumocystis pneumonia (PCP) is well known and described in AIDS patients. Due to
      the increasing use of cytotoxic and immunosuppressive therapies, the incidence of
      this infection has dramatically increased in the last years in patients with
      other predisposing immunodeficiencies and remains an important cause of morbidity
      and mortality in solid-organ transplant (SOT) recipients. PCP in HIV-negative
      patients, such as SOT patients, harbors some specificity compared to AIDS
      patients, which could change the medical management of these patients. This
      article summarizes the current knowledge on the epidemiology, risk factors,
      clinical manifestations, diagnoses, prevention, and treatment of Pneumocystis
      pneumonia in solid-organ transplant recipients, with a particular focus on the
      changes caused by the use of post-transplantation prophylaxis.

PMID- 29376916
TI  - Pushing the Limits of MALDI-TOF Mass Spectrometry: Beyond Fungal Species
      Identification.
AB  - Matrix assisted laser desorption ionization time of flight (MALDI-TOF) is a
      powerful analytical tool that has revolutionized microbial identification.
      Routinely used for bacterial identification, MALDI-TOF has recently been applied
      to both yeast and filamentous fungi, confirming its pivotal role in the rapid and
      reliable diagnosis of infections. Subspecies-level identification holds an
      important role in epidemiological investigations aimed at tracing virulent or
      drug resistant clones. This review focuses on present and future applications of
      this versatile tool in the clinical mycology laboratory.

PMID- 29376917
TI  - The Biological Diversity and Production of Volatile Organic Compounds by Stem
      Inhabiting Endophytic Fungi of Ecuador.
AB  - Fungal endophytes colonize every major lineage of land plants without causing
      apparent harm to their hosts. Despite their production of interesting and
      potentially novel compounds, endophytes-particularly those inhabiting stem
      tissues-are still a vastly underexplored component of microbial diversity. In
      this study, we explored the diversity of over 1500 fungal endophyte isolates
      collected from three Ecuadorian ecosystems: lowland tropical forest, cloud
      forest, and coastal dry forest. We sought to determine whether Ecuador's fungal
      endophytes are hyperdiverse, and whether that biological diversity is reflected
      in the endophytes' chemical diversity. To assess this chemical diversity, we
      analyzed a subset of isolates for their production of volatile organic compounds
      (VOCs), a representative class of natural products. This study yielded a total of
      1526 fungal ITS sequences comprising some 315 operational taxonomic units (OTUs),
      resulting in a non-asymptotic OTU accumulation curve and characterized by a
      Fisher's alpha of 120 and a Shannon Diversity score of 7.56. These figures
      suggest that the Ecuadorian endophytes are hyperdiverse. Furthermore, the 113
      isolates screened for VOCs produced more than 140 unique compounds. These results
      present a mere snapshot of the remarkable biological and chemical diversity of
      stem-inhabiting endophytic fungi from a single neotropical country.

PMID- 29376919
TI  - Phaeohyphomycosis in Transplant Patients.
AB  - Phaeohyphomycosis is caused by a large, heterogenous group of darkly pigmented
      fungi. The presence of melanin in their cell walls is characteristic, and is
      likely an important virulence factor. These infections are being increasingly
      seen in a variety of clinical syndromes in both immunocompromised and normal
      individuals. Transplant patients are especially at risk due their prolonged
      immunosuppression. There are no specific diagnostic tests for these fungi, though
      the Fontana-Masson stain is relatively specific in tissue. They are generally
      seen in a worldwide distribution, though a few species are only found in specific
      geographic regions. Management of these infections is not standardized due to
      lack of clinical trials, though recommendations are available based on clinical
      experience from case reports and series and animal models. Superficial infections
      may be treated without systemic therapy. Central nervous system infections are
      unique in that they often affect otherwise normal individuals, and are difficult
      to treat. Disseminated infections carry a high mortality despite aggressive
      therapy, usually with multiple antifungal drugs. Considerable work is needed to
      determine optimal diagnostic and treatment strategies for these infections.

PMID- 29376918
TI  - Masking the Pathogen: Evolutionary Strategies of Fungi and Their Bacterial
      Counterparts.
AB  - Pathogens reduce immune recognition of their cell surfaces using a variety of
      inert structural polysaccharides. For example, capsular polysaccharides play
      critical roles in microbial survival strategies. Capsules are widely distributed
      among bacterial species, but relatively rare in eukaryotic microorganisms, where
      they have evolved considerable complexity in structure and regulation and are
      exemplified by that of the HIV/AIDS-related fungus Cryptococcus neoformans.
      Endemic fungi that affect normal hosts such as Histoplasma capsulatum and
      Blastomyces dermatitidis have also evolved protective polysaccharide coverings in
      the form of immunologically inert alpha-(1,3)-glucan polysaccharides to protect
      their more immunogenic beta-(1,3)-glucan-containing cell walls. In this review we
      provide a comparative update on bacterial and fungal capsular structures and
      immunogenic properties as well as the polysaccharide masking strategies of
      endemic fungal pathogens.

PMID- 29376920
TI  - Colliding Epidemics and the Rise of Cryptococcosis.
AB  - Discovered more than 100 years ago as a human pathogen, the Cryptococcus
      neoformans-Cryptococcus gattii (C. neoformans-C. gattii) complex has seen a large
      global resurgence in its association with clinical disease in the last 30 years.
      First isolated in fermenting peach juice, and identified as a human pathogen in
      1894 in a patient with bone lesions, this environmental pathogen has now found
      niches in soil, trees, birds, and domestic pets. Cryptococcosis is well
      recognized as an opportunistic infection and was first noted to be associated
      with reticuloendothelial cancers in the 1950s. Since then, advances in transplant
      immunology, medical science and surgical techniques have led to increasing
      numbers of solid organ transplantations (SOT) and hematological stem cell
      transplantations being performed, and the use of biological immunotherapeutics in
      increasingly high-risk and older individuals, have contributed to the further
      rise in cryptococcosis. Globally, however, the major driver for revivification of
      cryptococcosis is undoubtedly the HIV epidemic, particularly in Sub-Saharan
      Africa where access to care and antiretroviral therapy remains limited and
      advanced immunodeficiency, poverty and malnutrition remains the norm. As a
      zoonotic disease, environmental outbreaks of both human and animal cryptococcosis
      have been reported, possibly driven by climate change. This is best exemplified
      by the resurgence of C. gattii infection in Vancouver Island, Canada, and the
      Pacific Northwest of the United States since 1999. Here we describe how the
      colliding epidemics of HIV, transplantation and immunologics, climate change and
      migration have contributed to the rise of cryptococcosis.

PMID- 29376921
TI  - Microsporidiosis in Vertebrate Companion Exotic Animals.
AB  - Veterinarians caring for companion animals may encounter microsporidia in various
      host species, and diagnosis and treatment of these fungal organisms can be
      particularly challenging. Fourteen microsporidial species have been reported to
      infect humans and some of them are zoonotic; however, to date, direct zoonotic
      transmission is difficult to document versus transit through the digestive tract.
      In this context, summarizing information available about microsporidiosis of
      companion exotic animals is relevant due to the proximity of these animals to
      their owners. Diagnostic modalities and therapeutic challenges are reviewed by
      taxa. Further studies are needed to better assess risks associated with animal
      microsporidia for immunosuppressed owners and to improve detection and treatment
      of infected companion animals.

PMID- 29376922
TI  - Severe Dermatophytosis and Acquired or Innate Immunodeficiency: A Review.
AB  - Dermatophytes are keratinophilic fungi responsible for benign and common forms of
      infection worldwide. However, they can lead to rare and severe diseases in
      immunocompromised patients. Severe forms include extensive and/or invasive
      dermatophytosis, i.e., deep dermatophytosis and Majocchi's granuloma. They are
      reported in immunocompromised hosts with primary (autosomal recessive CARD9
      deficiency) or acquired (solid organ transplantation, autoimmune diseases
      requiring immunosuppressive treatments, HIV infection) immunodeficiencies. The
      clinical manifestations of the infection are not specific. Lymph node and organ
      involvement may also occur. Diagnosis requires both mycological and histological
      findings. There is no consensus on treatment. Systemic antifungal agents such as
      terbinafine and azoles (itraconazole or posaconazole) are effective. However,
      long-term outcome and treatment management depend on the site and extent of the
      infection and the nature of the underlying immunodeficiency.

PMID- 29376923
TI  - Pediatric Invasive Candidiasis: Epidemiology and Diagnosis in Children.
AB  - Pediatric patients present with differing underlying conditions and cytotoxic
      therapeutic protocols, so the differing epidemiology of invasive candidiasis in
      children versus adults is not surprising. Understanding the Candida species
      epidemiology is critical, as we often begin empiric therapy or therapy before
      antifungal susceptibilities are known. Reports with newer molecular diagnostic
      assays for invasive candidiasis are rare and require more study to develop firm
      pediatric-specific guidance. Antifungal treatment of pediatric candidiasis is
      reviewed in the context of larger epidemiologic studies and the few trials
      completed to date.

PMID- 29376924
TI  - Transcriptomic Crosstalk between Fungal Invasive Pathogens and Their Host Cells:
      Opportunities and Challenges for Next-Generation Sequencing Methods.
AB  - Fungal invasive infections are an increasing health problem. The intrinsic
      complexity of pathogenic fungi and the unmet clinical need for new and more
      effective treatments requires a detailed knowledge of the infection process.
      During infection, fungal pathogens are able to trigger a specific transcriptional
      program in their host cells. The detailed knowledge of this transcriptional
      program will allow for a better understanding of the infection process and
      consequently will help in the future design of more efficient therapeutic
      strategies. Simultaneous transcriptomic studies of pathogen and host by high
      throughput sequencing (dual RNA-seq) is an unbiased protocol to understand the
      intricate regulatory networks underlying the infectious process. This protocol is
      starting to be applied to the study of the interactions between fungal pathogens
      and their hosts. To date, our knowledge of the molecular basis of infection for
      fungal pathogens is still very limited, and the putative role of regulatory
      players such as non-coding RNAs or epigenetic factors remains elusive. The wider
      application of high-throughput transcriptomics in the near future will help to
      understand the fungal mechanisms for colonization and survival, as well as to
      characterize the molecular responses of the host cell against a fungal infection.

PMID- 29376926
TI  - Genome Studies on Nematophagous and Entomogenous Fungi in China.
AB  - The nematophagous and entomogenous fungi are natural enemies of nematodes and
      insects and have been utilized by humans to control agricultural and forestry
      pests. Some of these fungi have been or are being developed as biological control
      agents in China and worldwide. Several important nematophagous and entomogenous
      fungi, including nematode-trapping fungi (Arthrobotrys oligospora and
      Drechslerella stenobrocha), nematode endoparasite (Hirsutella minnesotensis),
      insect pathogens (Beauveria bassiana and Metarhizium spp.) and Chinese medicinal
      fungi (Ophiocordyceps sinensis and Cordyceps militaris), have been genome
      sequenced and extensively analyzed in China. The biology, evolution, and
      pharmaceutical application of these fungi and their interacting with host
      nematodes and insects revealed by genomes, comparing genomes coupled with
      transcriptomes are summarized and reviewed in this paper.

PMID- 29376927
TI  - Invasive Candidiasis in Various Patient Populations: Incorporating Non-Culture
      Diagnostic Tests into Rational Management Strategies.
AB  - Mortality rates due to invasive candidiasis remain unacceptably high, in part
      because the poor sensitivity and slow turn-around time of cultures delay the
      initiation of antifungal treatment. beta-d-glucan (Fungitell) and polymerase
      chain reaction (PCR)-based (T2Candida) assays are FDA-approved adjuncts to
      cultures for diagnosing invasive candidiasis, but their clinical roles are
      unclear. We propose a Bayesian framework for interpreting non-culture test
      results and developing rational patient management strategies, which considers
      test performance and types of invasive candidiasis that are most common in
      various patient populations. beta-d-glucan sensitivity/specificity for candidemia
      and intra-abdominal candidiasis is ~80%/80% and ~60%/75%, respectively. In
      settings with 1%-10% likelihood of candidemia, anticipated beta-d-glucan positive
      and negative predictive values are ~4%-31% and >=97%, respectively. Corresponding
      values in settings with 3%-30% likelihood of intra-abdominal candidiasis are ~7%
      51% and ~78%-98%. beta-d-glucan is predicted to be useful in guiding antifungal
      treatment for wide ranges of populations at-risk for candidemia (incidence ~5%
      40%) or intra-abdominal candidiasis (~7%-20%). Validated PCR-based assays should
      broaden windows to include populations at lower-risk for candidemia (incidence
      >=~2%) and higher-risk for intra-abdominal candidiasis (up to ~40%). In the
      management of individual patients, non-culture tests may also have value outside
      of these windows. The proposals we put forth are not definitive treatment
      guidelines, but rather represent starting points for clinical trial design and
      debate by the infectious diseases community. The principles presented here will
      be applicable to other assays as they enter the clinic, and to existing assays as
      more data become available from different populations.

PMID- 29376928
TI  - Omics for Investigating Chitosan as an Antifungal and Gene Modulator.
AB  - Chitosan is a biopolymer with a wide range of applications. The use of chitosan
      in clinical medicine to control infections by fungal pathogens such as Candida
      spp. is one of its most promising applications in view of the reduced number of
      antifungals available. Chitosan increases intracellular oxidative stress, then
      permeabilizes the plasma membrane of sensitive filamentous fungus Neurospora
      crassa and yeast. Transcriptomics reveals plasma membrane homeostasis and
      oxidative metabolism genes as key players in the response of fungi to chitosan. A
      lipase and a monosaccharide transporter, both inner plasma membrane proteins, and
      a glutathione transferase are main chitosan targets in N. crassa. Biocontrol
      fungi such as Pochonia chlamydosporia have a low content of polyunsaturated free
      fatty acids in their plasma membranes and are resistant to chitosan. Genome
      sequencing of P. chlamydosporia reveals a wide gene machinery to degrade and
      assimilate chitosan. Chitosan increases P. chlamydosporia sporulation and
      enhances parasitism of plant parasitic nematodes by the fungus. Omics studies
      allow understanding the mode of action of chitosan and help its development as an
      antifungal and gene modulator.

PMID- 29376929
TI  - Colony-PCR Is a Rapid Method for DNA Amplification of Hyphomycetes.
AB  - Fungal pure cultures identified with both classical morphological methods and
      through barcoding sequences are a basic requirement for reliable reference
      sequences in public databases. Improved techniques for an accelerated DNA barcode
      reference library construction will result in considerably improved sequence
      databases covering a wider taxonomic range. Fast, cheap, and reliable methods for
      obtaining DNA sequences from fungal isolates are, therefore, a valuable tool for
      the scientific community. Direct colony PCR was already successfully established
      for yeasts, but has not been evaluated for a wide range of anamorphic soil fungi
      up to now, and a direct amplification protocol for hyphomycetes without tissue
      pre-treatment has not been published so far. Here, we present a colony PCR
      technique directly from fungal hyphae without previous DNA extraction or other
      prior manipulation. Seven hundred eighty-eight fungal strains from 48 genera were
      tested with a success rate of 86%. PCR success varied considerably: DNA of fungi
      belonging to the genera Cladosporium, Geomyces, Fusarium, and Mortierella could
      be amplified with high success. DNA of soil-borne yeasts was always successfully
      amplified. Absidia, Mucor, Trichoderma, and Penicillium isolates had noticeably
      lower PCR success.

PMID- 29376930
TI  - Exploitation of Aspergillus terreus for the Production of Natural Statins.
AB  - The fungus Aspergillus (A.) terreus has dominated the biological production of
      the "blockbuster" drugs known as statins. The statins are a class of drugs that
      inhibit HMG-CoA reductase and lead to lower cholesterol production. The statins
      were initially discovered in fungi and for many years fungi were the sole source
      for the statins. At present, novel chemically synthesised statins are produced as
      inspired by the naturally occurring statin molecules. The isolation of the
      natural statins, compactin, mevastatin and lovastatin from A. terreus represents
      one of the great achievements of industrial microbiology. Here we review the
      discovery of statins, along with strategies that have been applied to scale up
      their production by A. terreus strains. The strategies encompass many of the
      techniques available in industrial microbiology and include the optimization of
      media and fermentation conditions, the improvement of strains through classical
      mutagenesis, induced genetic manipulation and the use of statistical design.

PMID- 29376931
TI  - Preemptive Therapy for Cryptococcal Meningitis: A Valid Strategy for Latin
      America?
AB  - AIDS-related cryptococcal meningitis continues to cause a substantial burden of
      death in low and middle income countries. Better diagnostics allow detection of
      cryptococcosis in the asymptomatic phase and using these technologies to screen
      at-risk persons would likely reduce mortality. The World Health Organization
      recommends cryptococcal antigen screening among populations with a prevalence of
      cryptococcal antigenaemia (CRAG) > 3%. There is scarce data about CRAG prevalence
      in Latin America. Four studies (only one published as a full text) showed
      asymptomatic CRAG prevalence between 2.7% and 6.2% in several sub-sets of HIV
      infected patients. The CRAG lateral flow assay (LFA) has several advantages over
      other techniques for actual implementation of a screening program. Although more
      studies are necessary to confirm available data, implementation of the CRAG
      screening strategy seems to be opportune in Latin America.

PMID- 29376932
TI  - Aspergillosis in Chronic Granulomatous Disease.
AB  - Patients with chronic granulomatous disease (CGD) have the highest life-time
      incidence of invasive aspergillosis and despite the availability of antifungal
      prophylaxis, infections by Aspergillus species remain the single most common
      infectious cause of death in CGD. Recent developments in curative treatment
      options, such as haematopoietic stem cell transplantation, will change the
      prevalence of infectious complications including invasive aspergillosis in CGD
      patients. However, invasive aspergillosis in a previously healthy host is often
      the first presenting feature of this primary immunodeficiency. Recognizing the
      characteristic clinical presentation and understanding how to diagnose and treat
      invasive aspergillosis in CGD is of utmost relevance to improve clinical
      outcomes. Significant differences exist in fungal epidemiology, clinical signs
      and symptoms, and the usefulness of non-culture based diagnostic tools between
      the CGD host and neutropenic patients, reflecting underlying differences in the
      pathogenesis of invasive aspergillosis shaped by the nicotinamide adenine
      dinucleotide phosphate (NADPH)-oxidase deficiency.

PMID- 29376933
TI  - Low Titer Pneumocystis jirovecii Infections: More than Just Colonization?
AB  - Non-pneumonia Pneumocystis jirovecii colonization is thought to occur frequently
      in immunocompetent individuals. The aim was to analyze if P. jirovecii low-titer
      detections have more impact than just colonization. From our total cohort of
      patients for which P. jirovecii testing by qPCR was requested, we selected
      exclusively those that were fully immunocompetent. Patients were defined as fully
      immunocompetent if they did not receive immunosuppressive therapy, displayed
      regular antibody titers, and did not suffer from acquired, inherited or
      autoimmune diseases. Only those patients with complete medical records available
      were included. A retrospective analysis identified patients with P. jirovecii
      colonization and successful antibiotic therapy in response to laboratory pathogen
      detection. We identified 30 fully immunocompetent patients with P. jirovecii
      colonization suspected to suffer from infection with the pathogen, but with
      milder symptoms than pneumonia. All patients were successfully treated with
      cotrimoxazole against P. jirovecii and resolved from chronic cough and recurrent
      pulmonary infections. The fact that all patients displayed recovery from their
      clinical symptoms gives raise to the hypothesis that P. jirovecii infections may
      also occur in immunocompetent patients but with milder symptoms.

PMID- 29376934
TI  - Allergic Bronchopulmonary Aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA), a progressive fungal allergic
      lung disease, is a common complication of asthma or cystic fibrosis. Although
      ABPA has been recognized since the 1950s, recent research has underscored the
      importance of Th2 immune deviation and granulocyte activation in its
      pathogenesis. There is also strong evidence of widespread under-diagnosis due to
      the complexity and lack of standardization of diagnostic criteria. Treatment has
      long focused on downregulation of the inflammatory response with prolonged
      courses of oral glucocorticosteroids, but more recently concerns with steroid
      toxicity and availability of new treatment modalities has led to trials of oral
      azoles, inhaled amphotericin, pulse intravenous steroids, and subcutaneously
      injected anti-IgE monoclonal antibody omalizumab, all of which show evidence of
      efficacy and reduced toxicity.

PMID- 29376937
TI  - Galactomannan and 1,3-beta-d-Glucan Testing for the Diagnosis of Invasive
      Aspergillosis.
AB  - Invasive aspergillosis (IA) is a severe complication among hematopoietic stem
      cell transplant recipients or patients with hematological malignancies and
      neutropenia following anti-cancer therapy. Moreover, IA is increasingly observed
      in other populations, such as solid-organ transplant recipients, patients with
      solid tumors or auto-immune diseases, and among intensive care unit patients.
      Frequent delay in diagnosis is associated with high mortality rates. Cultures
      from clinical specimens remain sterile in many cases and the diagnosis of IA
      often only relies on non-specific radiological signs in the presence of host risk
      factors. Tests for detection of galactomannan- (GM) and 1,3-beta-d-glucan (BDG)
      are useful adjunctive tools for the early diagnosis of IA and may have a role in
      monitoring response to therapy. However, the sensitivity and specificity of these
      fungal biomarkers are not optimal and variations between patient populations are
      observed. This review discusses the role and interpretation of GM and BDG testing
      for the diagnosis of IA in different clinical samples (serum, bronchoalveolar
      lavage fluid, cerebrospinal fluid) and different groups of patients (onco
      hematological patients, solid-organ transplant recipients, other patients at risk
      of IA).

PMID- 29376936
TI  - Pediatric Invasive Aspergillosis.
AB  - Invasive aspergillosis (IA) is a disease of increasing importance in pediatrics
      due to growth of the immunocompromised populations at risk and improvements in
      long-term survival for many of these groups. While general principles of
      diagnosis and therapy apply similarly across the age spectrum, there are unique
      considerations for clinicians who care for children and adolescents with IA. This
      review will highlight important differences in the epidemiology, clinical
      manifestations, diagnosis, and therapy of pediatric IA.

PMID- 29376935
TI  - Chronic Pulmonary Aspergillosis-Where Are We? and Where Are We Going?
AB  - Chronic pulmonary aspergillosis (CPA) is estimated to affect 3 million people
      worldwide making it an under recognised, but significant health problem across
      the globe, conferring significant morbidity and mortality. With variable disease
      forms, high levels of associated respiratory co-morbidity, limited therapeutic
      options and prolonged treatment strategies, CPA is a challenging disease for both
      patients and healthcare professionals. CPA can mimic smear-negative tuberculosis
      (TB), pulmonary histoplasmosis or coccidioidomycosis. Cultures for Aspergillus
      are usually negative, however, the detection of Aspergillus IgG is a simple and
      sensitive test widely used in diagnosis. When a fungal ball/aspergilloma is
      visible radiologically, the diagnosis has been made late. Sometimes weight loss
      and fatigue are predominant symptoms; pyrexia is rare. Despite the efforts of the
      mycology community, and significant strides being taken in optimising the care of
      these patients, much remains to be learnt about this patient population, the
      disease itself and the best use of available therapies, with the development of
      new therapies being a key priority. Here, current knowledge and practices are
      reviewed, and areas of research priority highlighted.

PMID- 29376939
TI  - Correction: Kwon-Chung, K.J. et al. Is Cryptococcus gattii a Primary Pathogen? J.
      Fungi 2015, 1, 154-167.
AB  - The authors of the published paper [1] would like to correct Table 1.[...].

PMID- 29376938
TI  - Triazole Resistance in Aspergillus spp.: A Worldwide Problem?
AB  - Since the first description of an azole-resistant A. fumigatus strain in 1997,
      there has been an increasing number of papers describing the emergence of azole
      resistance. Firstly reported in the USA and soon after in Europe, it has now been
      described worldwide, challenging the management of human aspergillosis. The main
      mechanism of resistance is the modification of the azole target enzyme: 14-alpha
      sterol demethylase, encoded by the cyp51A gene; although recently, other
      resistance mechanisms have also been implicated. In addition, a shift in the
      epidemiology has been noted with other Aspergillus species (mostly azole
      resistant) increasingly being reported as causative agents of human disease. This
      paper reviews the current situation of Aspergillus azole resistance and its
      implications in the clinical setting.

PMID- 29376940
TI  - PCR Technology for Detection of Invasive Aspergillosis.
AB  - The application of molecular technologies to aid diagnosis and management of
      infectious diseases has had a major impact and many assays are in routine use.
      Diagnosis of aspergillosis has lagged behind. Lack of standardization and limited
      commercial interest have meant that PCR was not included in consensus diagnostic
      criteria for invasive fungal disease. In the last ten years careful evaluation
      and validation by the Aspergillus European PCR initiative with the development of
      standardized extraction, amplification and detection protocols for various
      specimen types, has provided the opportunity for clinical utility to be
      investigated. PCR has the potential to not only exclude a diagnosis of invasive
      aspergillosis but in combination with antigen testing may offer an approach for
      the early diagnosis and treatment of invasive aspergillosis in high-risk
      populations, with the added benefit of detection of genetic markers associated
      with antifungal resistance.

PMID- 29376942
TI  - Treatment of Primary Pulmonary Aspergillosis: An Assessment of the Evidence.
AB  - Aspergillus spp. are a group of filamentous molds that were first described due
      to a perceived similarity to an aspergillum, or liturgical device used to
      sprinkle holy water, when viewed under a microscope. Although commonly inhaled
      due to their ubiquitous nature within the environment, an invasive fungal
      infection (IFI) is a rare outcome that is often reserved for those patients who
      are immunocompromised. Given the potential for significant morbidity and
      mortality within this patient population from IFI due to Aspergillus spp., along
      with the rise in the use of therapies that confer immunosuppression, there is an
      increasing need for appropriate initial clinical suspicion leading to accurate
      diagnosis and effective treatment. Voriconazole remains the first line agent for
      therapy; however, the use of polyenes, novel triazole agents, or voriconazole in
      combination with an echinocandin may also be utilized. Consideration as to which
      particular agent and for what duration should be made in the individual context
      for each patient based upon underlying immunosuppression, comorbidities, and
      overall tolerance of therapy.

PMID- 29376941
TI  - Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery.
AB  - Opportunistic fungi are a major cause of morbidity and mortality world-wide,
      particularly in immunocompromised individuals. Developing new treatments to
      combat invasive fungal disease is challenging given that fungal and mammalian
      host cells are eukaryotic, with similar organization and physiology. Even
      therapies targeting unique fungal cell features have limitations and drug
      resistance is emerging. New approaches to the development of antifungal drugs are
      therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal
      meningitis worldwide, is an accepted model for studying fungal pathogenicity and
      driving drug discovery. We recently characterized a phospholipase C (Plc1)
      dependent pathway in C. neoformans comprising of sequentially-acting inositol
      polyphosphate kinases (IPK), which are involved in synthesizing inositol
      polyphosphates (IP). We also showed that the pathway is essential for fungal
      cellular function and pathogenicity. The IP products of the pathway are
      structurally diverse, each consisting of an inositol ring, with phosphate (P) and
      pyrophosphate (PP) groups covalently attached at different positions. This review
      focuses on (1) the characterization of the Plc1/IPK pathway in C. neoformans; (2)
      the identification of PP-IP5 (IP7) as the most crucial IP species for fungal
      fitness and virulence in a mouse model of fungal infection; and (3) why IPK
      enzymes represent suitable candidates for drug development.

PMID- 29376944
TI  - Correction: Stewart, E.R.; Thompson, G.R. Treatment of Primary Pulmonary
      Aspergillosis: An Assessment of the Evidence. J. Fungi 2016, 2, 25.
AB  - The authors of the published paper [1] would like to correct Table 1.[...].

PMID- 29376943
TI  - New Horizons in Antifungal Therapy.
AB  - Recent investigations have yielded both profound insights into the mechanisms
      required by pathogenic fungi for virulence within the human host, as well as
      novel potential targets for antifungal therapeutics. Some of these studies have
      resulted in the identification of novel compounds that act against these pathways
      and also demonstrate potent antifungal activity. However, considerable effort is
      required to move from pre-clinical compound testing to true clinical trials, a
      necessary step toward ultimately bringing new drugs to market. The rising
      incidence of invasive fungal infections mandates continued efforts to identify
      new strategies for antifungal therapy. Moreover, these life-threatening
      infections often occur in our most vulnerable patient populations. In addition to
      finding completely novel antifungal compounds, there is also a renewed effort to
      redirect existing drugs for use as antifungal agents. Several recent screens have
      identified potent antifungal activity in compounds previously indicated for other
      uses in humans. Together, the combined efforts of academic investigators and the
      pharmaceutical industry is resulting in exciting new possibilities for the
      treatment of invasive fungal infections.

PMID- 29376945
TI  - Phylogenetic Analysis of the Synnema-Producing Genus Synnemapestaloides.
AB  - Synnemapestaloides rhododendri, the type species of the genus Synnemapestaloides,
      is a pathogen of Rhododendron brachycarpum. This fungus produces six-celled
      conidia with appendages at both end cells, and are generated by annellidic
      conidiogenous cells on the synnema. These conidial structures are similar to
      those of the genus Pestalotia. The monotypic genus Synnemapestaloides is
      currently classified in the family Amphisphaeriaceae solely based on conidial
      morphology. Here we demonstrate that Synnemapestaloides represents a distinct
      genus in the family Sporocadaceae (Amphisphaeriales) based on differences in the
      nucleotide sequences of the partial large subunit rDNA gene, the rDNA internal
      transcribed spacer, and the partial beta-tubulin. The genus most closely related
      to Synnemapestaloides is Seimatosporium and the species most similar to
      Synnemapestaloides rhododendri is Seim. foliicola which produces short synnema
      like conidiomata (sporodochia). These results demonstrate that Seim. foliicola
      should be transferred to Synnemapestaloides, and also demonstrate that
      Sporocadaceae can have synnematal in addition to pycnidial and acervular
      conidiomata.

PMID- 29376947
TI  - Special Issue "Aspergillus fumigatus: From Diagnosis to Therapy".
AB  - Aspergillus fumigatus is an enigmatic pathogen.

PMID- 29376946
TI  - Virulence Factors as Targets for Anticryptococcal Therapy.
AB  - The global mortality due to cryptococcosis caused by Cryptococcus neoformans or
      C. gattii is unacceptably high. Currently available therapies are decades old and
      may be impacted by drug resistance. Therefore, the need for more effective
      antifungal drugs for cryptococcosis is evident. A number of Cryptococcus
      virulence factors have been studied in detail, providing crucial information
      about the fungal biology and putative molecular targets for antifungals. This
      review focuses on the use of well-described virulence factors of Cryptococcus as
      potential anticryptococcal agents.

PMID- 29376949
TI  - The Quest for a Vaccine Against Coccidioidomycosis: A Neglected Disease of the
      Americas.
AB  - Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of
      Coccidioides spp. This neglected disease has substantial public health impact
      despite its geographic restriction to desert areas of the southwestern U.S.,
      Mexico, Central and South America. The incidence of this infection in California
      and Arizona has been increasing over the past fifteen years. Several large cities
      are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000
      hospital admissions per year in California. While most cases of
      coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require
      anti-fungal treatment, and a significant number disseminate beyond the lungs.
      Disseminated infection involving the meninges is fatal without appropriate
      treatment. Infection with Coccidioides spp. is protective against a second
      infection, so vaccination seems biologically plausible. This review of efforts to
      develop a vaccine against coccidioidomycosis focuses on vaccine approaches and
      the difficulties in identifying protein antigen/adjuvant combinations that
      protect in experimental mouse models. Although the quest for a vaccine is still
      in the early stage, scientific efforts for vaccine development may pave the way
      for future success.

PMID- 29376950
TI  - [Surgical management of non-functioning pancreatic neuroendocrine tumors].
AB  - AIM: To analyze immediate and long-term results of surgical treatment of patients
      with non-functioning pancreatic neuroendocrine tumors (pNETs). MATERIAL AND
      METHODS: Outcomes in 21 patients with non-functioning pNETs were retrospectively
      analyzed. RESULTS: Long-term results were followed-up in 18 (85%) cases, median
      follow-up was 39 months. Postoperative mortality was 4.7%. The incidence of
      postoperative complications Clavien-Dindo degree IIIA and over was 20.8%, overall
      5-year survival - 89%, desease-free 5-year survival - 78%. CONCLUSION: At present
      time surgical intervention remains the only radical method of non-functioning
      pNETs management. Threshold tumor dimension should be 15 mm that determines
      surgical intervention or active surveillance. From an oncological point of view
      tumor enucleation is permissible only in case of small dimensions (up to 2 cm)
      and full confidence in low degree of malignancy. Lymphadenectomy should be
      performed in all cases in standard fashion because lymph node involvement is
      reliably poor prognostic sign.

PMID- 29376951
TI  - [Perforated cholecystitis. Classification and atypical clinical forms].
AB  - AIM: To obtain new data for diagnosis and treatment of patients with perforated
      cholecystitis. MATERIAL AND METHODS: It was analyzed the variants of original
      classification of perforated cholecystitis by Fedorov S.P. - Neimeier O.W.
      (1934). Moreover, we have assessed treatment of 292 patients with gallbladder
      perforation (own material of Faculty Surgery Clinic). RESULTS: According to
      continuous 20-year follow-up perforated cholecystitis was observed in 2.9% of
      patients with various forms of gallbladder inflammation (n=292 out of 10 215).
      The frequency of atypical clinical forms of gallbladder perforation including
      multiple and combined perforation, perforation with acute intestinal obstruction
      and intraabdominal bleeding was 10% (n=29 of 292). Overall mortality in atypical
      clinical forms related to whole cohort with perforated cholecystitis was 2% (n=6
      of 292). CONCLUSION: Atypical clinical forms of gallbladder perforation require
      specific treatment strategy due to the need for emergency surgical interventions.
      At the same time, the possibilities of video-assisted surgery are somewhat
      limited compared with other forms of gallbladder inflammation and can be used
      only in a third of patients.

PMID- 29376952
TI  - [Effect of different nutritional support on pancreatic secretion in acute
      pancreatitis].
AB  - AIM: To develop and justify optimal nutritional support in early phase of acute
      pancreatitis (AP). MATERIAL AND METHODS: 140 AP patients were enrolled. They were
      divided into groups depending on nutritional support: group I (n=70) - early
      enteral tube feeding (ETF) with balanced mixtures, group II (n=30) - early ETF
      with oligopeptide mixture, group III (n=40) - total parenteral nutrition (TPN).
      The subgroups were also isolated depending on medication: A - Octreotide, B -
      Quamatel, C - Octreotide + Quamatel. Pancreatic secretion was evaluated by using
      of course of disease, instrumental methods, APUD-system hormone levels (secretin,
      cholecystokinin, somatostatin, vasointestinal peptide). RESULTS: ETF was followed
      by pancreas enlargement despite ongoing therapy, while TPN led to gradual
      reduction of pancreatic size up to normal values. alpha-amylase level
      progressively decreased in all groups, however in patients who underwent ETF (I
      and II) mean values of the enzyme were significantly higher compared with TPN
      (group III). Secretin, cholecystokinin and vasointestinal peptide were increasing
      in most cases, while the level of somatostatin was below normal in all groups.
      CONCLUSION: Enteral tube feeding (balanced and oligopeptide mixtures) contributes
      to pancreatic secretion compared with TPN, but this negative impact is eliminated
      by antisecretory therapy. Dual medication (Octreotide + Quamatel) is more
      preferable than monotherapy (Octreotide or Quamatel).

PMID- 29376948
TI  - Allergic Aspergillus Rhinosinusitis.
AB  - Allergic fungal rhinosinusitis (AFRS) is a unique variety of chronic polypoid
      rhinosinusitis usually in atopic individuals, characterized by presence of
      eosinophilic mucin and fungal hyphae in paranasal sinuses without invasion into
      surrounding mucosa. It has emerged as an important disease involving a large
      population across the world with geographic variation in incidence and
      epidemiology. The disease is surrounded by controversies regarding its definition
      and etiopathogenesis. A working group on "Fungal Sinusitis" under the
      International Society for Human and Animal Mycology (ISHAM) addressed some of
      those issues, but many questions remain unanswered. The descriptions of
      "eosinophilic fungal rhinosinusitis" (EFRS), "eosinophilic mucin rhinosinusitis"
      (EMRS) and mucosal invasion by hyphae in few patients have increased the problem
      to delineate the disease. Various hypotheses exist for etiopathogenesis of AFRS
      with considerable overlap, though recent extensive studies have made certain in
      depth understanding. The diagnosis of AFRS is a multi-disciplinary approach
      including the imaging, histopathology, mycology and immunological investigations.
      Though there is no uniform management protocol for AFRS, surgical clearing of the
      sinuses with steroid therapy are commonly practiced. The role of antifungal
      agents, leukotriene antagonists and immunomodulators is still questionable. The
      present review covers the controversies, recent advances in pathogenesis,
      diagnosis, and management of AFRS.

PMID- 29376953
TI  - [Antegrade approach for cholangiolithiasis complicated by mechanical jaundice].
AB  - AIM: To improve an efficiency of surgical treatment of patients with
      cholelithiasis complicated by obstructive jaundice through antegrade
      interventional approach. MATERIAL AND METHODS: 166 patients aged from 23 to 92
      years with cholangiolithiasis complicated by mechanical jaundice were enrolled.
      Patients were divided into 2 groups: group I (136) - retrograde endoscopic
      method, group II (30) - antegrade interventional approach. RESULTS: In the first
      group surgical efficacy was 79.4%. Morbidity and mortality were 13% and 2%
      respectively. In the second group these values were 96.7%, 10% and 3%
      respectively. CONCLUSION: Antegrade interventional approach for minimally
      invasive procedures is technically feasible, has the same effectiveness as the
      retrograde endoscopic method and also all advantages of minimally invasive
      techniques.

PMID- 29376954
TI  - [An efficacy of carotid arteries repair for tortuosity combined with stenosis].
AB  - AIM: To assess an efficacy of carotid arteries reconstruction in patients with
      internal carotid artery stenosis combined with tortuosity. MATERIAL AND METHODS:
      86 patients with ICA tortuosity and stenosis were enrolled. All patients were
      divided into groups depending on type of surgery: group I - open carotid
      endarterectomy (CEA) followed by obligatory repair with synthetic patch (31 (36%)
      patients); group II - eversion CEA with ICA resection, redressation and
      reimplantation into own ostium (35 (40.7%) patients); group III - ICA replacement
      (20 (23.3%) patients). Synthetic prosthesis and autovein were used in 13 (65%)
      and 7 (35%) patients respectively. The study included patients with ICA stenosis
      >=60% (any type of plaque) and any degree of cerebrovascular insufficiency or ICA
      stenosis <60% (plaque type I-III) with CVI grade II-IV combined with S- or C
      tortuosity, bend or loop with blood flow velocity over 110 cm/s and its
      turbulence. Only 6 (7.0%) out of 86 patients had no clinical signs of
      CVI/previous stroke. Asymptomatic/symptomatic patients ratio was following in all
      groups: group I - 12 (38.7%)/19 (61.3%); group II - 29 (82.9%)/6 (17.1%); group
      III - 10 (50%)/10 (50%). RESULTS: Within 6-month follow-up 22 (70.9%) out of 31
      patients were asymptomatic in group I, 30 (85.7%) (p=0.9475) out of 35 - in group
      II, 9 (45%) (p=0.9511) out of 20 patients - in group III and 1 (5%) patient
      developed thrombosis of the reconstruction zone followed by ischemic stroke.
      After 12 months following patients were asymptomatic: 22 (70.9%) in group I, 30
      (85.7%) (p=0.9475) in group II and 9 (45%) patients (p=0.9511) in group III.
      After 1 year 4 (33.3%) out of 12 patients with CVI grade IV had partial
      regression of focal neurological symptoms. CONCLUSION: Surgery for ICA tortuosity
      combined with stenosis confirmed its efficacy and safety for both asymptomatic
      and symptomatic patients. Significantly better results were observed in eversion
      CEA compared with conventional procedure and ICA replacement.

PMID- 29376955
TI  - [Pathogenesis and prevention of venous and arterial thromboembolic events in
      patients after deep vein thrombosis of lower extremities].
AB  - AIM: To define the role of thrombophilic and other procoagulant conditions in
      pathogenesis of deep vein thrombosis and the effectiveness of pathogenetic
      secondary prevention of venous and arterial thromboembolic events. MATERIAL AND
      METHODS: The study included 107 patients for the period 2007-2016 who were
      divided into 3 groups. The main group (n=40) - lifelong individual antithrombotic
      therapy with warfarin predominantly; the second (control) group (n=39) - warfarin
      administration for 3-6 months; the third (additional) group (n=28) - specific
      life-long therapy depending on procoagulant status which was assessed according
      to original scale. The main anticoagulants were rivoroxaban or dabigatran
      etexilate. Recurrent venous thromboembolic complications (RVTE) were observed in
      one (2.5%) patient of the first group and in 8 (20.5%) cases of the second group.
      In the third group RVTE were absent (significant differences, p<0.03 and 0.001,
      respectively). Arterial thromboembolic diseases were noted in 1 (2.5%) patient of
      the first group, in 4 (10.25%) cases of the second group and in none of the third
      group (significantly only for group II vs. group III, p<0.01). RESULTS:
      Individual antithrombotic therapy reduces the incidence of recurrent venous and
      arterial thromboembolic events in patients with idiopathic deep vein thrombosis.

PMID- 29376956
TI  - [Treatment of advanced age patients with polytrauma through lethal outcome risk
      assessment].
AB  - AIM: To objectify timing of DCS stages implementation in advanced age patients
      through lethal outcome risk assessment. MATERIAL AND METHODS: 128 advanced age
      patients with polytrauma were enrolled. RESULTS: It was concluded that
      specialized prognosis scale for advanced age patients with polytrauma allowed to
      objectify the transition time between DCS stages that led to decrease of
      mortality by 10.6%.

PMID- 29376957
TI  - ['Conservative' organ-sparing approach for ovarian torsion in children].
AB  - AIM: To improve the outcomes in children with ovarian torsion. MATERIAL AND
      METHODS: Three clinical observations of patients with ovarian torsion are
      presented. Duration of the disease was 3-4 days. All children underwent organ
      sparing surgery including untwisting followed by ovariopexy. RESULTS: All
      children were examined in early and late postoperative period (up to 5 years)
      after organ-sparing procedures. Ultrasonic picture of the ovaries including
      structure and dimensions corresponded to age, the follicles were determined.
      CONCLUSION: 'Conservative' approach allows to preserve anatomical structure and
      potential for reproductive function.

PMID- 29376958
TI  - [Law and educational components of patient's safety in surgery].
AB  - AIM: To evaluate law and educational components of patient's safety (PS) in
      surgery. MATERIAL AND METHODS: In order to analyze complex causes of adverse
      outcomes in surgery we performed an interviewing of 110 surgeons, 42 emergency
      physicians and 25 health care managers. The main keynote consisted in assessing
      law and educational components of PS. RESULTS: The study revealed significant
      professional shortcomings in law PS level and low educational and motivational
      activity of physicians of all specialties. CONCLUSION: Multi-faceted nature of PS
      problem requires multidisciplinary training of modern surgeons not only in the
      knowledge of key risk factors for adverse outcomes, but also in satisfaction of
      non-medical expectations of patients. Due to numerous objective reasons Russian
      surgical school should have the opportunity not to blindly copy the experience of
      our foreign colleagues, but to scientifically substantiate the development of own
      national security system both for surgical patients and medical workers
      themselves.

PMID- 29376959
TI  - [Clinical experience with the use of rivaroxaban in the treatment of cancer
      patients with venous thrombosis].
AB  - : The urgency of the problem. The incidence of various thromboembolic
      complications in patients with oncopathology reaches 5-12%. When treating VTE in
      patients with oncology it is necessary to choose between two generally recognized
      alternatives. The recommended two-component scheme of the initiating phase of
      anticoagulant therapy with subsequent long-term admission of VKA is fraught with
      the development of clinically significant bleeding during the initial selection
      of the dose of warfarin and an increased risk of recurrence of VTE. Long-term
      parenteral use of LMWH is often negatively treated by patients and adversely
      affects compliance. For these reasons, enteral administration of new oral
      anticoagulants is promising for prolonged anticoagulant therapy in this category
      of patients. The paper cites three clinical cases of treatment of patients with
      acute venous thrombosis of deep veins against a background of different
      oncological processes. In the first case - the operated previously for cancer, in
      the second case - to be treated over oncological process and in the third case -
      in the primary cancer detection. DISCUSSION: The results of the studies of
      EINSTEIN-DVT and EINSTEIN-PE allow us to consider the use of rivaroxaban in the
      treatment of patients with VTE on the background of oncopathology. The
      possibility of its use from the first day, in our opinion, is a significant
      advantage, since it allows us to reveal the clinical effectiveness of
      anticoagulant therapy already during the first stage of treatment, since NOAKs
      does not imply the possibility of laboratory monitoring.

PMID- 29376960
TI  - [Surgical treatment of lung cancer combined with advanced atherosclerosis under
      intra-aortic balloon counterpulsation].

PMID- 29376961
TI  - [Chylothorax management after bilateral bi-directional cavopulmonary
      anastomosis].

PMID- 29376962
TI  - [Acute mesenteric venous thrombosis in pregnant women with thrombophilia and
      doubled inferior vena cava].

PMID- 29376963
TI  - [Valved conduits in pediatric cardiac surgery].

PMID- 29376964
TI  - [Perioperative complications prognosis in carotid endarterectomy].

PMID- 29376965
TI  - [Surgical treatment of benign tumors and tumor-like diseases of hand bones].

PMID- 29376966
TI  - [Nanobiomedical technologies in surgery].

PMID- 29376967
TI  - [Diagnosis and treatment of seroma after anterior abdominal wall hernia repair by
      using of mesh implant].

PMID- 29376968
TI  - [The non-medicamentous methods for the prevention and treatment of the patients
      presenting with neurocirculatory asthenia and concomitant enhanced
      meteosensitivity].
AB  - OBJECTIVE: The relevance of the problem stated in the title of this article comes
      from the significant increase in the prevalence of the functional cardiovascular
      disorders having been documented during the past years especially such as
      circulatory asthenia that most frequently affects the young people of the working
      age suffering from the systemic neurogenic imbalance in the organism and can be
      seriously aggravated by the influence of biotropic weather conditions and be
      responsible for enhanced meteosensitivity that has negative effect on the quality
      of life and impairs the effectiveness of the therapeutic interventions. AIM:  The
      objective of the present study was to provide the scientifically sound
      substantiation of the feasibility of the application of the non-medicamentous
      methods (including the interval hypoxic training and "dry" carbonic baths) for
      the prevention and treatment of neurocirculatory asthenia complicated by enhanced
      meteosensitivity and evaluate the therapeutic effectiveness of these approach.
      MATERIAL AND METHODS:  A total of 50 patients with the verified diagnosis of
      neurocirculatory asthenia were recruited to participate in the study. All the
      patients were divided into two groups. 62% of them exhibited the well apparent
      meteosensitivity and were included in the study group 1. Group 2 was comprised of
      the remaining patients (38% of their total number) presenting with
      neurocirculatory asthenia who did not suffer appreciable changes in the general
      physical and mental state under the influence of varying weather conditions. The
      patients of both groups received the identical combined treatment consisting of
      interval hypoxic training and taking "dry" carbonic baths. Monitoring of the main
      meteorological parameters was carried out on a daily basis. It was combined with
      the assessment of the weather conditions from the medical perspective, the
      evaluation of the physical performance capability of the patients based on the
      results of the veloergometric testing, and the estimation of their functional
      state of the autonomous nervous system with the use of the data obtained in
      cardiointervalographic studies. In addition, the state of the microcirculatory
      system was evaluated by means of laser Doppler flowmetry and making use of a
      capillary blood flow analyzer. The psychological status of the patients was
      characterized using a computer-generated version of the abridged multifactorial
      questionnaire for the elucidation of the manifest personality-scale anxiety
      (Spielbeger's State-Trait Anxiety Inventory). All these studies were carried out
      both before and after the course of non-medicamentous therapy. RESULTS:  After
      the course of the combined non-medicamentous treatment had been completed the
      health status of the patients comprising the two groups was found to be improved
      as appeared from the decrease of the number and severity of subjective autonomous
      manifestations, the positive changes in the functional state of the
      cardiovascular system and the autonomic nervous system as well as in the general
      psychological status. The most clinically significant result of the treatment
      included the reduction in the incidence of the severe meteopathic reactions in
      the patients of group 2 (from 14% before to 3% after therapy). The frequency of
      moderately expressed meteopathic reactions likewise decreased (from 31% before to
      14% after the treatment). CONCLUSIONS:  The study has demonstrated that under the
      environmental and climatic conditions of the of Moscow region formation of
      biotropic weather factors of the hypoxic type (39%) constitutes a serious risk
      factor contributing to the development of imbalance in the vegetative nervous
      system and its exacerbations in response to variations of weather parameters. The
      application of the non-medicamentous therapeutic modalities (including interval
      hypoxic training and "dry" carbonic baths) for the management of the
      meteosensitive patients presenting with neurocirculatory asthenia is
      pathogenetically justified, and they can be recommended for both the treatment
      and prevention of weather- dependent pathological processes and their
      exacerbations.

PMID- 29376969
TI  - [The commonest therapeutic methods for laser irradiation of blood].
AB  - One of the most widely employed methods of laser therapy is laser irradiation of
      blood (LIB). There are two modifications of this technique, one being intravenous
      low-intensity laser irradiation of blood (ILIB), the other non-invasive blood
      irradiation(NLIB). The two methods have been developing independently since
      either has its advantages and disadvantages. The present article was designed to
      review the main currently available techniques for laser irradiation of blood
      which are presented in the form of tables (charts). Replacing the UV irradiation
      of blood with UV lamps by laser ultraviolet irradiation of blood (LUVIB(r)) has
      made it possible to significantly simplify the technique and enhanced its
      efficiency. The most effective options for ILIB are the combined techniques: ILIB
      635 + LUVIB(r) and ILIB-525 + LUVIB. The most effective technique for ELIB is
      believed to be the use of low-intensity pulsed laser light with a wavelength of
      635 nm and output power up to 40 W.

PMID- 29376970
TI  - [The experimental evaluation of the protective effect of the extract of the
      cyclodextrin-containing phytotherapeutic composition on the development of
      osteoporosis].
AB  - OBJECTIVE: The relevance of the problem considered in the present communication
      arises to-day from the widespread prevalence of osteoporosis (OP), the rather low
      effectiveness of the methods currently available for the treatment of this
      condition, and iatrogenic effects of its medication therapy. The great diversity
      of phytotherapeutic modalities of traditional medicine are is only poorly
      supported by the results of the scientific studies results; moreover, most of
      them are coming from the foreign literature publications. AIM:  The objective of
      the present study was to evaluate the influence of the phytotherapeutic
      preparation (Phytocost) having cyclodextrin in its composition on the restoration
      of the cartilaginous and bony tissues based on the experimental research with the
      use of the OP experimental model. MATERIAL AND METHODS:  The experimental studies
      were performed on 5 month-old Balb/c mice used as the prednisolone-induced
      osteoporosis model. The animals were divided into four study groups according to
      the daily doses administered to them: 0.005; 0.05; 0.5 and 5.0 mg/mouse during 30
      days and 3 control groups: intact, 14 and 30 days after prednisolone
      administration, naive mice. RESULTS:  The study has demonstrated the dose
      dependent protective effect of cyclodextrin-containing Phytocost. The most
      pronounced effect in the form of reduction of osteoblast number and the increase
      in the number of osteocytes was obtained at a Phytocost dose of 0.5 mg/mouse. No
      undesirable adverse reactions were documented during the study. CONCLUSION:  The
      domestically produced Phytocost composition differs from its foreign analogues in
      that it contains a significantly greater number of constituent components because
      the ultimate goal of the study was to create a medication acting on all currently
      known mechanisms of OP pathogenesis, whereas our Chinese colleagues proceed from
      the ancient knowledge gained by traditional medicine that it is sometimes
      difficult to understand and explain in the light of the modern concepts. All the
      plants used as raw materials for Phytocost production grow at the territory of
      the Russian Federation which provides the possibilities for the efficient import
      substitution of the components necessary for the manufacture of the preparation
      in question.

PMID- 29376971
TI  - [One-time effects of drinking mineral water and tap water enriched with silver
      nanoparticles on the biochemical markers of liver condition and metabolic
      parameters in healthy rats].
AB  - AIM:  The objective of the present research was to study the influence of tap
      water enriched with silver nanoparticles (NP) as well as that of "Krasnoarmeysky"
      and "Essentuki No17" mineral waters after their single administration through the
      oral gavage to the rats on the metabolism of carbohydrates and lipids, the
      biochemical markers of the liver condition, and the endocrine profile in the
      healthy animals. MATERIAL AND METHODS:  The laboratory animals (130 male Wistar
      rats) were allocated to thirteen groups comprised of 10 rats each as follows: 1st
      group (n=10) intact animals, 2nd group (5 minutes after the administration of
      silver NP (n=10), 3rd group (15 minutes after the of silver NP), 4th group (60
      minutes after the administration of silver NP), 5th group (n=10) (5 minutes after
      the introduction of the "Krasnoarmeysky" mineral water), 6th group (n=10) (15 min
      after the introduction of the "Krasnoarmeysky" mineral water), 7th group (n=10),
      (60 minutes after the introduction of the "Krasnoarmeysky" mineral water) 8th
      group (n=10) (5 minutes after the introduction of the "Essentuki No 17" mineral
      water), 9th group (n=10) (15 min after the introduction of the "Essentuki No 7"
      mineral water) , 10th group (n=10) (60 minutes after the introduction of the
      "Essentuki No17" mineral water), 11th group (n=10) (5 minutes after
      administration of tap water (control),12th group (n=10) (15 minutes after
      administration of tap water (control), and 13th (n=10) group 60 minutes after
      administration of tap water (control). RESULTS:  The study has demonstrated that
      the tap water enriched with silver nanoparticles similar to the mineral waters
      caused stress reactions that are inferior to those induced by "Essentuki No17"
      mineral water in terms of the magnitude; however, the effect provoked by the tap
      water was of longer duration. Moreover, the tap water enriched with silver
      nanoparticles stimulates prooxidant reactions, and inhibit the activity of
      antioxidant protection. Silver nanoparticles appear to produce some destructive
      effect on the hepatocytes. CONCLUSION:  The silver nanoparticles present in the
      tap water have a significant biological potential of their own. Moreover, their
      one-time action is apt to alter the biological potential of the water into which
      they are administered. The single intake of the tap water enriched with silver
      nanoparticles by the healthy laboratory animals produces the response that
      resembles that of the drinking mineral water.

PMID- 29376972
TI  - [The peculiar hydrogeochemical features of the hydrosphere in the regions of salt
      dome tectonics (as exemplified by the giant salt domes of the Peri-Caspian
      Lowland megabasin)].
AB  - The Peri-Caspian Lowland megabasin is a vast region of ancient salt accumulation
      that occurred during the Permian period. The territory over which the salt domes
      were formed gave rise to and accumulated huge resources of subterranean brackish
      and salted waters within the hypergenesis zone that also included brine and
      mineral mud lakes containing chemical elements of great therapeutic value.
      Nowadays, the subterranean waters (leaches, pools, and springs) provide the
      sources of the mineral-rich materials of balneological significance, such as
      sulfide, bromine, and boron-containing mineral waters the ion and mineral
      composition of which together with the high degree of mineralization makes them
      highly valuable for medicinal applications. Both leaches and peloids are
      extensively used in chemical industry and cosmetology. Brine lakes of the Peri
      Caspian Depression are hypersaline lake water bodies with waters of the chlorine
      magnesium type having marine origin. These lakes are fed by ground waters
      (especially those coming from the salt springs) in the combination with
      atmospheric precipitation. The chemical composition of brine and peloids of lakes
      Inder and Baskunchak is characterized by the high degree of mineralization with
      sodium chloride the concentration of which amounts to 264 i 325 g/dm3
      respectively. The natural brine of the lake Inder contains the following
      biologically active components: Br - 460 mg/dm3 and H3BO3 - 100 mg/dm3. The
      territories surrounding the lakes Inder, Baskunchak, and El'ton are the sources
      of salt-saturated sulfide-silty muds characterized by a high degree of
      mineralization (250-306 mg/dm3) due to the presence of 0,15-0,50% of FeS. In
      addition, they contain biologically active bromine and borates, besides hydrogen
      sulphide. The ground-water discharge sites at the territories around lakes Inder
      and Baskunchak are located largely in the vicinity of the Permian sulphate
      halogen deposits. The springs bring mostly water with the enhanced content of
      sodium chloride and the high degree of mineralization ranging from 20-30 g/dm3 to
      150 g/dm3. They can be considered to be the analogues of waters of the Usol'skiy,
      Staroruskiy, ands Vologodskiy types and are highly suitable for the application
      for the purpose of balneotherapy.

PMID- 29376973
TI  - [The modular strategy for the informational support of medical activities based
      at the spa and health resort facilities under conditions of infrastructure
      deficit].
AB  - The Crimean peninsula, by virtue of its unique geographical conditions, has a
      variety of natural resources providing a basis for the maintenance of the health
      resort activities in the region. However, most local health centers suffer from
      the chronic and difficultly avoidable in the short term problems with logistical
      support, including the shortage of computers and the lack of modern network
      infrastructure. This circumstance limits the deployment capabilities of high
      grade medical information systems for the automation of all components of the
      activity of health resorts and the significant improvement of the performance of
      other aspects of their work, such as efficient patient routing, workflow
      optimization, limiting the opportunities for the realization of certain
      corruption schemes by the staff. We have studied the routing of patients and the
      associated document flow in a number of Crimean spa and health resort facilities
      (sanatoriums). As a result, the basic work places at which information contained
      in the documents is undergoing changes were identified. Based on these data, the
      basic (modular) concept of the development of medical information system was
      formulated. According to the principle of modularity, the structure of the
      information system has been modified and optimized. The stages of implementation
      of this approach at various levels of logistic facilities were described, defined
      and justified. The key feature of the proposed system consists in that even the
      minimal equipment of computing infrastructure units (starting from a single
      workplace, such as a "medical receptionist") may be sufficient to achieve the
      significant degree of automation in the workflow, provide monitoring and analysis
      of the medical records of the spa and health resort facilities. By gradually
      increasing the number of related automated workplaces and modules, it is possible
      to expand the capabilities of the system up to the full automation of a given
      health resort facility.

PMID- 29376974
TI  - [Rehabilitation of the patients presenting with the operated spine syndrome
      during the complicated postoperative period after discectomy].
AB  - This article presents an analytical review of the literature concerning the
      problem of rehabilitation of the patients following the surgical treatment of
      hernias of intervertebral disks. The relevance of this problem and the importance
      of the related research activities in the context of neurorehabilitation are
      beyond any doubt. Despite the obvious progress in the modernization of the
      methods and technologies for medical rehabilitation, the number of re-operations
      in connection with the recurrences of herniated discs remains too high and the
      overall success thus far achieved in this field falls short of expectations. The
      authors discuss in detail the need for and the contemporary approaches to the
      rehabilitative treatment of the patients undergoing vertebral microdiscectomy
      including medication therapy, physiotherapy an therapeutic physical exercises.
      The variants of the application of magnetic stimulation during the early period
      of the rehabilitative treatment of the patients following the minimally invasive
      interventions for discogenic radiculopathy are considered.

PMID- 29376975
TI  - [Skin receptors and therapeutic physical factors].
AB  - This review presents the data on the receptor function of the skin and its role
      in the formation of the body's response to the action of physical therapy.
      Especially much attention is given in the paper to the influence of ultrasound,
      microwaves, laser radiation, various medical environments, and other physical
      factors on the morphofunctional condition of the skin receptors. Possible
      mechanisms of changes in receptor activity under effects of physical therapeutic
      factors are analyzed. Moreover, the paper summarizes the directions of further
      possible studies on the interactions between physical factors and cutaneous
      receptors.

PMID- 29376976
TI  - [The feasibility of the application of cryotherapy and radonotherapy for the
      treatment of the patients presenting with osteoarthritis].
AB  - Osteoarthritis (OA) is currently considered to be one of the most widespread
      diseases. Its main clinical symptoms include pain and dysfunction of joints. In
      the present review of the foreign and domestic literature, the questions of
      pathogenesis and risk factors underlying the development of osteoarthritis are
      discussed. The understanding of OA pathogenesis have altered essentially in the
      recent years which made necessary the search for the novel approaches to the
      treatment of this pathology. According to the modern views of OA origin and
      progression, its therapy should be based on the application of the combination of
      medicamentous and non-medicamentous modalities including, in particular,
      collective and individual activities focused on the implementation of the
      programs of therapeutic physical training as an obligatory component of OA
      prophylaxis and treatment. The present review gives evidence of the feasibility
      of the application of the methods of cryotherapy and radonotherapy for the
      management of the patients suffering from osteoarthritis. It is emphasized that
      many recent publications report extensive investigations of the clinical and
      pathogenetic aspects of the application of these methods for the combined
      regenerative treatment of the patients presenting with gonarthrosis. The
      influence of cryotherapy and radonotherapy on the neuroendocrine and immune
      systems is discussed with special reference to the possibility of regulation of
      the metabolic processes and retardation of inflammation. It is concluded that the
      introduction of the above methods into the compulsory individual program for the
      regenerative treatment of patients presenting with osteoarthritis is
      pathologically substantiated since it greatly contributes to the reduction of
      pain and retardation of the progress of the disease. The main pharmaceutical
      preparations for the OA treatment remain to be slow-acting symptomatic medicines
      possessed of the chondro-protective effect.

PMID- 29376977
TI  - [Emotional and personality characteristics of patients with dystonia].
AB  - AIM: To examine emotional characteristics, especially personality profile, of
      patients with dystonia. MATERIAL AND METHODS: Three hundred patients with
      dystonia were enrolled in the study. Control groups consisted of 50 healthy
      individuals and 62 patients with hemifacial spasm (GFS). HADS, Beck depression
      inventory and Spielberger-Khanin anxiety scale were used. The 16 Personality
      Factors Questionnaire (16PF) was used to study personality profile. RESULTS AND
      CONCLUSION: Higher levels of anxiety and depression in patients with dystonia
      compared to the control groups were identified. The level of anxiety and
      depression was not correlated with disease severity. Personality profile study
      confirmed the high level of anxiety in patients with dystonia and additionally
      showed increased emotional instability and poor emotional control. Intellectual
      personality characteristics of patients with dystonia had no differences compared
      to the control groups. An analysis of socio-psychological characteristics of
      personality in patients with dystonia and GFS showed restricted interpersonal and
      social communications since the motor defect noticeable to others leads to severe
      social exclusion and the desire for self-isolation.

PMID- 29376978
TI  - [Endogenous episodes of juvenile psychosis with religious delusions].
AB  - AIM: To identify clinical and psychopathological features, conditions of
      formation and prognostic significance of delusions with religious content in
      endogenous psychotic states in adolescence. MATERIAL AND METHODS: Fifty-three
      male patients, aged from 16 to 25 years, with juvenile endogenous psychosis, with
      a psychotic episode with religious content of delusion were examined. Clinical,
      psychopathological, psychometrical (The Dawkins scale) and statistical methods
      were used. RESULTS AND CONCLUSION: General psychopathological features of
      psychotic states with religious delusions, according to the specificity of
      adolescent age, were identified. Common types of religious delusional episodes,
      forming by primal interpretive (delusion of sin, delusion of demonic possession)
      and sensual (messianic and antagonistic delusion, religious oneiroid) mechanisms
      were distinguished. A role of the previous religiosity, including overvalued
      religious ideas, was clarified. It was found out that the duration of the pre
      manifest stage, hospitalization and the period of 'untreated psychosis', was
      longer in patients with religious delusions compared to patients with other types
      of delusions. Patients with interpretive mechanism of delusion formation
      demonstrated the subsequent intensification of religiosity that was not common
      for psychotic episodes with the sensual mechanism of delusion formation.

PMID- 29376979
TI  - [Differential approaches to the treatment of acute psychosis due to the use of
      synthetic cannabinoids].
AB  - Based on the study of 43 patients with acute psychosis due to the use of
      synthetic cannabinoids, the authors showed that the inclusion of neuroleptic
      drugs in the complex therapy increases the efficacy of therapy. In choosing a
      neuroleptic it is important to take into account not only the psychopathological
      structure of psychosis, but also the severity of somatic and neurological
      disorders associated with psychosis.

PMID- 29376980
TI  - [Syndrome dopamine dysregulation and deep brain stimulation of the subthalamic
      nucleus in Parkinson's disease].
AB  - AIM: Dopamine dysregulation syndrome (DDS) is a complication of the dopaminergic
      therapy in Parkinson's disease (PD); it is manifested as a compulsive medication
      use and may have negative impact on patients' social, psychological, and physical
      functioning. An effect of deep brain stimulation in the subthalamic nucleus (DBS
      STN) on DDS is not fully understood. Therefore, the degree of DDS during DBS STN
      in PD patients was evaluated in the study. MATERIAL AND METHODS: The main group
      included 15 patients with DDS symptoms in the preoperative period. The comparison
      group consisted of 15 patients without DDS symptoms and the control group
      consisted of 15 patients who did not undergo surgery. RESULTS AND CONCLUSION: The
      severity of motor disturbances in the surgery groups has decreased significantly
      (by 45%). Motor complications during DBS STN in patients with DDS have decreased
      by 50%; a decrease in the reduction of doses of dopaminergic preparations was
      noted as well.

PMID- 29376981
TI  - [The efficacy of botulinotherapy in the correction of the pain syndrome and
      quality of life of patients with cervical dystonia].
AB  - AIM: To evaluate the severity of pain, emotional status and humoral serotonin in
      patients with cervical dystonia (CD) before and after the botulinotherapy.
      MATERIAL AND METHODS: A simple, open, comparative study of clinical
      characteristics of hyperkinesis, pain and emotional status, quality of life and
      contents of serum and blood platelet serotonin in 48 patients (32 women and 16
      men) with CD, in age from 37 to 53 years, before and one month after the
      botulinotherapy with disport in dose of 500--1000 U was carried out. A control
      group included 15 healthy people. RESULTS: All patients (100%) complained of
      involuntary movements and pain in the neck. The overall score on a scale of
      dystonic movements in the group of patients was 16,7+/-7,7 points, on TWSTRS -
      46,48+/-6,2 points, on the Visual Analogue Scale, the average level of pain was
      6,4+/-1,08 points. The degree of depression according to the Hamilton scale was
      significantly higher (p<0.05) compared to the control group. The level of trait
      and state anxiety measured with the Spielberger-Khanin scale was significantly
      higher (p<0.005) in patients with CD than in the controls. The correlation
      analysis revealed a direct dependence of the intensity of pain subscale TWSTRS
      with the degree of anxiety on the Hamilton scale and the amount of final points
      of dystonic movements. The level of serotonin in the serum was significantly
      lower in patients compared to the controls. After botulinotherapy, pain scores,
      anxiety and depression have significantly decreased and the level of blood
      platelet serotonin has increased. CONCLUSION: Botulinotherapy with dysport in CD
      patients reduces the degree of pain, depression, improves quality of life and
      stimulates the serotoninergic system.

PMID- 29376982
TI  - [The efficacy of prevention of postoperative cognitive dysfunction in cardiac
      surgeries with the use of the cerebrolysin].
AB  - AIM: To assess the efficacy of postoperative cytoprotection with cerebrolysin in
      cardiac surgeries without using cardiopulmonary bypass and to analyze the changes
      in the blood circulation in the postoperative period in groups with- and without
      cerebrolysin preconditioning. MATERIAL AND METHODS: Thirty-eight patients, who
      underwent coronary and mammaro-coronary bypass grafting without using
      cardiopulmonary bypass, were included in the study. Fifteen patients received
      cerebrolysin before surgery. RESULTS AND CONCLUSION: Cerebrolysin improved
      cognitive test scores. Positive changes on anxiety and depression scales were
      observed as well. In the group of patients treated with cerebrolysin,
      quantitative parameters of the cerebral blood flow were in stable condition, with
      a slight increase on the 10th day after surgery, which may indicate increasing
      stress resistance of cells of the central nervous system after appropriate
      pharmacological protection.

PMID- 29376983
TI  - [Antiinflammatory treatment in patients with chronic back pain].
AB  - : Non-steroidal anti-inflammatory drugs (NSAIDs) are part of the treatment of
      patients with chronic nonspecific back pain (CBP). An analysis of the reasons for
      the absence of NSAIDs administration or cancellation of previously iniciated
      NSAIDs in patients with CBP was the goal of this study. MATERIAL AND METHODS: We
      analyzed the peculiarities of treatment of CBP in 250 patients at baseline and
      after 1 and 2 years. The features of drug therapy, the reasons for therapy
      cancellation were evaluated. RESULTS AND CONCLUSION: 52 (20.8%) of patients with
      CBP were not treated with NSAIDs, 38 (15.2%) recieved NSAIDs in 4 and > days per
      week, 44 (17.6%) - 3 and < days a week, 62 (24.8%) took NSAID in 7-14 day 2-5
      times per year, 54 (21.6%) - in on-demand mode. Absence of NSAIDs administration
      in CBP was associated with older age, the presence of comorbidites, with non
      alcoholic fatty liver disease and obesity. The cancelletion of previously
      initiated NSAID was equally associated with the resolution of pain and with the
      failure to respond to therapy, with the presence of obesity and with the intake
      of nonselective NSAIDs. Continuation of the initiated effective anti-inflammatory
      therapy was associated with the use of coxibs, complex treatment with the use of
      neirobion, with the presence of normal body weight, and with the achievement of a
      decrease in the severity of the pain syndrome even in the absence of its complete
      resolution. Increased adherence to treatment with NSAIDs in CBP patients can be
      achieved by increasing of its effectiveness through the use of NSAIDs (especially
      coxibs) with B group vitamins (B1, B6, B12), by normalizing of BMI and
      effectively controlling liver function.

PMID- 29376984
TI  - [Neurosonography of the facial nerve in children with idiopathic neuropathy of
      facial nerve].
AB  - AIM: To find the correlation between neurophysiological and neurosonographic
      (NSG) parameters of the facial nerve of children with idiopathic neuropathy of
      the facial nerve (NLN) in the acute period with good and poor prognosis of
      recovery of facial nerve function. MATERIAL AND METHODS: Sixty-five children with
      NLN (mean age 11.5+/-4.9 years) and 57 children of control group (mean age 12.5+/
      5.2 years) were examined. All children with NLN were studied using NSG with the
      measurement of the diameter of the facial nerve in the area of processus
      stylomastoideus and in the parotid gland. Stimulation electroneuromyography of
      the facial nerve with the registration of the M-response from the m. orbicularis
      oculi and evaluation of the degree of paresis of facial muscles using the 6-point
      House-Brackmann scale on the 10-15 day were performed. On the 30th day after
      manifestation of paresis, children with NLN were divided into two groups: the
      good recovery group 1 (n=54) and the poor prognosis recovery group (n=11).
      Correlation between NSG and electroneuromyography indicators with good and poor
      prognosis of recovery of facial nerve function was analyzed. RESULTS AND
      CONCLUSION: Based on the results obtained, 85% sensitivity and 77% specificity of
      measuring the diameter of the facial nerve using NSG in predicting poor prognosis
      of recovery of facial nerve function was shown. Normative and thresholds NSG
      parameters of the facial nerve in children were obtained.

PMID- 29376985
TI  - [Latent and simple forms of schizophrenia in the concept of E. Bleuler].
AB  - E. Bleuler's concept of latent schizophrenia, its relationship with the form of
      simple schizophrenia and the foundation of the idea that each form of
      schizophrenia can be latent are analyzed. Bleuler's interpretation of the meaning
      of different psychopathological symptoms for the diagnosis of schizophrenia and
      some innate contradictions of his diagnostic approach (declared criteria of
      absoluteness) are discussed. Different influences of Bleuler's concept on the
      following national concepts of schizophrenia and its development in the Russian
      psychiatry are noted.

PMID- 29376986
TI  - [Pathogenesis of endothelial dysfunction in cerebral atherosclerosis and their
      correction].
AB  - The authors review the studies on oxidative stress in the pathogenesis of
      cerebrovascular diseases (CVD) and highlight a contribution of endothelial
      dysfunction to the CVD development. Own experience of using divasa in patients of
      old and very old age with chronic CVD comorbid to cerebral atherosclerosis is
      described.

PMID- 29376987
TI  - [A study of the neuroprotective effect of mexidol on the cell model of glutamate
      stress].
AB  - AIM: To study a neuroprotective effect of mexidol on the cell model of glutamate
      stress. MATERIAL AND METHODS: Cytological studies of an effect of glutamate
      stress on cerebellar granule cells were carried out. RESULTS: Mexidol increased
      neuronal survival after the addition of glutamate by 8-10% (p<0.05). The effect
      of mexidol was more pronounced at the stage of neuron culture growth (5 days),
      cell survivability increased on average by 20%. CONCLUSION: The results of the
      study confirmed the neuroprotective effect of mexidol in the neuronal culture in
      glutamate toxicity model.

PMID- 29376988
TI  - [Pathogenesis of cognitive disorders in patients with Duchenne muscular
      dystrophy].
AB  - AIM: Clarification of the pathogenesis of cognitive disorders in patients with
      Duchenne muscular dystrophy in the clinical laboratory and molecular genetic
      study. MATERIAL AND METHODS: Thirty-six male patients with Duchenne muscular
      dystrophy (DMD), aged from 5 to 22 years (mean age 13.7 years), were examined.
      The control group consisted of 30 healthy people (7-22 years old, mean age 13.8).
      The clinical, molecular-genetic and laboratory study was conducted. The search
      for mutations in the dystrophin gene was carried out using multiplex PCR and
      multiplex ligation-dependent probe amplification. The laboratory study included
      determination of neurotrophins: brain-derived neurotrophic factor (BDNF), nerve
      growth factor (NGF) and ciliary neurotrophic factor (CNTF) using immunoenzyme
      method in serum. RESULTS AND CONCLUSION: Severe cognitive impairment was found in
      33% of patients with DMD. The distribution of mutations in the DMD gene was not
      uniform, most often the mutations were found in the region from exon 43 to exon
      50. Serum concentration of NGF in patients with DMD was higher than in the
      control group (2391 pg/ml [1587; 4136] and 553 pg / ml [314; 864], respectively
      (p<0.001)). In the group of patients with cognitive disorders, there was a
      decreased concentration of BGF (23 670 [21 700; 30 720] pg/ml (p<0.001)). In
      patients with BGF concentration less than 31 000 pg/ml, the chances of cognitive
      disorders were more than 10 times higher (p<0.001, odds ratio OR=12.0, 95% CI
      [1.9-76.4]). Thus, biochemical mechanisms, such as NGF overexpression and BGF
      deficiency, are involved in the development of cognitive disorders in patients
      with DMD.

PMID- 29376989
TI  - [Syndrome of mild encephalopathy with a reversible splenial corpus callosum
      lesion].
AB  - Mild encephalopathy with a reversible splenial lesion (MERS) is a clinico
      radiological syndrome that has been associated with a variety of underlying
      etiologies including viral and bacterial infections, epilepsy and antiepileptic
      drug cessation, hypoglycemia and electrolyte imbalance. We report a case of a 24
      year-old woman who had an isolated splenial lesion in the corpus callosum on
      neuroimaging associated with MERS.

PMID- 29376990
TI  - [REM-sleep behavior disorder and sleepwalking in a patient with Parkinson's
      disease and essential tremor].
AB  - REM-sleep behavior disorder (RBD), a form of parasomnia, is characterized by
      motor and/or speech activity during sleep corresponding to the dream content. RBD
      is currently considered as a marker of onset of neurodegenerative diseases
      (sinucleinopathies) and as a most specific early symptom of Parkinson's disease
      (PD). The authors describe a clinical case of a patient with the combination of
      essential tremor, initial signs of PD and RBD. A polysomnographic study has
      confirmed clinical signs of RBD and determined the disturbances of sleep
      architecture: the increase in falling asleep, number of awakenings, wakefulness
      during sleep, the absence of deep slow-wave sleep. The particular features of the
      patient were essential tremor and sleep walking.

PMID- 29376991
TI  - [Progressive multifocal encephalopathy in neurological practice].
AB  - Progressive multifocal leukoencephalopathy (PML) is considered so far as a rare
      rapidly progressive demyelinating CNS disease caused by the JC virus activation.
      Current data suggest that PML developed in people with impaired immunity.
      However, in some cases PML developed in the absence of severe immunological
      deficit. In clinical practice, the early diagnosis of PML is difficult because
      symptoms are mild and, therefore, the physician should be familiar with
      diagnostic criteria of this disease to make the correct diagnosis and start the
      symptomatic therapy as soon as possible. This will help to improve patient's
      state though there is no effective treatment of PML so far. Up to the present
      moment, antiviral medications, cytostatic drugs, serotonin receptor antagonists,
      plasmapheresis are widely used. These methods can be used only if the causes of
      PML have been identified while the patient needs urgent help. Thus, the schemes
      of pathogenetic treatment with the drugs with pleiotropic effects should be used.

PMID- 29376992
TI  - [Seven principles in the treatment of vestibular vertigo and results of the study
      of VIRTUOSO].
AB  - This article reports the results of the international post-marketing
      observational program VIRTUOSO aimed at the evaluation of the efficacy of
      betahistine dihydrochloride at the dose of 48 mg/day for 1-2 months in patients
      with paroxysmal vertigo of various origins. The clinical response was rated as
      good, very good or excellent in 74.1% of the patients (p<0.001). Monthly vertigo
      attack frequency with betahistine decreased in average from 8.0 to 3.0 (p<0.001).
      Vertigo attack frequency further decreased during the 2-month follow-up after the
      end of betahistine treatment. No serious adverse effects of betahistine have been
      reported.

PMID- 29376993
TI  - [Divasa in the treatment and prevention of cerebrovascular diseases].
AB  - Disturbances of hemorheology, hemostasis and fibrinolysis play an important role
      in the pathogenesis and pathophysiology of chronic cerebral ischemia.
      Physiological functioning of the endothelium is disturbed under the action of
      damaging factors. Divaza is created on the basis of release-active antibodies to
      S100b protein and antibodies to endothelial NO-synthase. The efficacy of divaza
      in the treatment of chronic cerebral ischemia and related diseases (cognitive
      impairment, anxiety) was demonstrated. A normalizing effect of divaza in the dose
      of 2 tablets 3 times daily between meals during 12 weeks on endothelial function
      is shown.

PMID- 29376994
TI  - [Dipyridamole in the treatment and prevention of cerebral venous thrombosis in
      women using hormonal contraceptives].
AB  - The review covers the topic of cerebral venous thrombosis (CVT) in women taking
      hormonal contraceptives. The paper gives the definition of CVT, the history and
      analysis of epidemiological data. It was shown that the increased risk of CVT
      occurs due to the influence of hormonal contraceptives on the system of
      hemostasis and severity of the risk depends on the preparation formula, the way
      and duration of its administration. The authors show the role of combination of
      hormonal contraceptives with other risk factors and predisposing conditions for
      the development of thrombosis. The rules for choosing the method of contraception
      in accordance with generally accepted recommendations are suggested. The
      description of pathogenic mechanisms of CVT, clinical picture and disease as well
      as neuroimaging criteria and the rules for choosing a diagnostic method are
      presented. The authors provide the description of complex therapy in the acute
      period of the disease, the rules for secondary prevention. Particular attention
      is paid to the possibility of using dipyridamole, which has a pleiotropic effect,
      influencing all the components of the Virchov triad, as a part of a complex
      therapy and secondary prevention.

PMID- 29376995
TI  - [A profile of antidepressive effects of agomelatine and a current view on the
      mechanism of its action].
AB  - Agomelatine is one of the latest antidepressants (melatoninergic agonists) with a
      new mechanism of action. From the positions of classical monoaminoergic theory,
      tts mechanism of action is difficult to understand, because the drug increases
      the levels of monoamines and neurotrophic factors, while not affecting their
      reuptake and negative feedback, which control neurotransmission level. Besides
      the effect on suprachiasmatic nucleus, a relevant role in the mechanism of action
      of agomelatine plays its special functionally selective (with regard to
      intracellular signaling pathways) interaction with heteromeric complexes of
      serotonin 5-NT2S and melatonin MT2 receptors in the hippocampus and cerebral
      cortex. Agomelatine is competitive to other modern antidepressants in the
      efficacy assessed by the percentage of complete responders and superior in the
      total frequency of remissions. Compared to other SSRI antidepressants,
      agomelatine is more effective for anhedonia. In these cases, agomelatine
      increases the level of brain-derived neurotrophic factor (BDNF) in the blood of
      responders.

PMID- 29376996
TI  - [Psychotherapy in treatment and rehabilitation of patients with multiple
      sclerosis].
AB  - Presented is a review of the use of psychotherapy and psychological intervention
      methods in treatment and rehabilitation of patients with multiple sclerosis (MS).
      Main indications for psychotherapy in MS are anxiety and depression, asthenia,
      movement disorders, cognitive decline or sleep disturbances. The applied methods
      of psychotherapy refer to behavioral, cognitive, humanistic, combined or
      alternative approaches. Individual and group sessions are most frequently used
      forms of psychotherapy. Positive effects of psychotherapy in MS patients are
      confirmed by data of randomized studies and neuroimaging. Psychotherapy should be
      included into complex multidisciplinary programs of treatment and rehabilitation
      of MS patients.

PMID- 29376997
TI  - [Primary headache - risk factor or comorbid pathology in cognitive impairment].
AB  - Currently, the relationship between headache and dementia is considered more
      widely than just a comorbidity. The severity of migraine and tension-type
      headache and the severity of cognitive impairment are strongly correlated. Common
      pathophysiological mechanisms underlie the relationship between primary headache
      and cognitive impairment. Antinociceptive changes in primary headaches and in
      glutamate excitotoxicity in dementia developed due to hyper excitability of NMDA
      receptors are strongly interdependent. It is important in the aspect of possible
      correction of this pathology by NMDA-antagonists. Memantine not only slows the
      progression of cognitive symptoms in dementia, but also significantly influences
      the frequency and severity of primary headache.

PMID- 29376998
TI  - [Modern technologies and prospects of rehabilitation of patients after ischemic
      stroke].
AB  - Despite the great achievements in the field of neurorehabilitation, a significant
      proportion of patients after an ischemic stroke have persistent motor
      disturbances even after timely and adequately carried out restorative measures.
      The article discusses the issues of neuroplasticity, modern diagnostic
      technologies for studying this phenomenon; prognostic factors for recovery
      deficit following stroke and determining the effectiveness of ongoing treatment.
      The principles of neuroprotective therapy in ischemic stroke are considered,
      which is a pathogenetically justified direction at all stages of restorative
      treatment after cerebral circulation disorders. One of the most studied original
      cytoprotectors, demonstrating safety, efficacy and good tolerability, is
      cytoflavin. The results of numerous clinical trials have revealed a significant
      positive clinical and morphological dynamics when taking cytoflavin in patients
      after ischemic stroke.

PMID- 29376999
TI  - [Phenazepam: to the question of the efficacy and safety of benzodiazepine
      derivatives].
AB  - The widespread use of benzodiazepines in general medicalpractice in patients with
      complaints of anxiety and insomnia is due to a combination of efficacy and
      relative safety. Benzodiazepines have several advantages over other groups of
      sedatives: a wider range of doses between anxiolytic and sedative effect, a
      higher ratio between the average lethal and average effective doses, the lower
      risk of abuse. However, with prolonged use of even therapeutic doses of
      benzodiazepines (more than 6 months), the risk of dependence may increase - more
      often with the use of high-potency short-acting drugs. Nevertheless, this risk
      with the correct use of drugs is greatly exaggerated. In many patients, prolonged
      therapy with benzodiazepines causes an improvement in the condition without the
      development of serious side effects. Do not abandon the use of this group of
      substances, following prejudices, but the appointment of benzodiazepines requires
      a thorough diagnostic assessment of the patient's condition and rational use of
      drugs.

PMID- 29377000
TI  - [New possibilities of treatment of low back pain].
AB  - Low back pain (LBP) is a syndrome caused by degenerative spine diseases and a
      common reason for referral for medical care. LBP is mostly often caused by
      osteoarthritis (OA) that needs long-term treatment with nonsteroidal anti
      inflammatory drugs. The treatment is associated with a risk of side-effects. The
      authors consider the possibility of using slow-acting drugs for symptomatic
      treatment of OA (SYSADOA) in patients with LBP and present the data on anti
      inflammatory effects of chondroitin sulfate on the chondral tissue in OA. The
      results of the studies on the use of SYSADOA in LBP are analyzed.

PMID- 29377001
TI  - Partial DNA-guided Cas9 enables genome editing with reduced off-target activity.
AB  - CRISPR-Cas9 is a versatile RNA-guided genome editing tool. Here we demonstrate
      that partial replacement of RNA nucleotides with DNA nucleotides in CRISPR RNA
      (crRNA) enables efficient gene editing in human cells. This strategy of partial
      DNA replacement retains on-target activity when used with both crRNA and sgRNA,
      as well as with multiple guide sequences. Partial DNA replacement also works for
      crRNA of Cpf1, another CRISPR system. We find that partial DNA replacement in the
      guide sequence significantly reduces off-target genome editing through focused
      analysis of off-target cleavage, measurement of mismatch tolerance and genome
      wide profiling of off-target sites. Using the structure of the Cas9-sgRNA complex
      as a guide, the majority of the 3' end of crRNA can be replaced with DNA
      nucleotide, and the 5 - and 3'-DNA-replaced crRNA enables efficient genome
      editing. Cas9 guided by a DNA-RNA chimera may provide a generalized strategy to
      reduce both the cost and the off-target genome editing in human cells.

PMID- 29377002
TI  - Lytic xylan oxidases from wood-decay fungi unlock biomass degradation.
AB  - Wood biomass is the most abundant feedstock envisioned for the development of
      modern biorefineries. However, the cost-effective conversion of this form of
      biomass into commodity products is limited by its resistance to enzymatic
      degradation. Here we describe a new family of fungal lytic polysaccharide
      monooxygenases (LPMOs) prevalent among white-rot and brown-rot basidiomycetes
      that is active on xylans-a recalcitrant polysaccharide abundant in wood biomass.
      Two AA14 LPMO members from the white-rot fungus Pycnoporus coccineus
      substantially increase the efficiency of wood saccharification through oxidative
      cleavage of highly refractory xylan-coated cellulose fibers. The discovery of
      this unique enzyme activity advances our knowledge on the degradation of woody
      biomass in nature and offers an innovative solution for improving enzyme
      cocktails for biorefinery applications.

PMID- 29377005
TI  - Dementia: Peripheral inflammation could be a prodromal indicator of dementia.

PMID- 29377003
TI  - Rewiring T-cell responses to soluble factors with chimeric antigen receptors.
AB  - Chimeric antigen receptor (CAR)-expressing T cells targeting surface-bound tumor
      antigens have yielded promising clinical outcomes, with two CD19 CAR-T cell
      therapies recently receiving FDA approval for the treatment of B-cell
      malignancies. The adoption of CARs for the recognition of soluble ligands, a
      distinct class of biomarkers in physiology and disease, could considerably
      broaden the utility of CARs in disease treatment. In this study, we demonstrate
      that CAR-T cells can be engineered to respond robustly to diverse soluble
      ligands, including the CD19 ectodomain, GFP variants, and transforming growth
      factor beta (TGF-beta). We additionally show that CAR signaling in response to
      soluble ligands relies on ligand-mediated CAR dimerization and that CAR
      responsiveness to soluble ligands can be fine-tuned by adjusting the mechanical
      coupling between the CAR's ligand-binding and signaling domains. Our results
      support a role for mechanotransduction in CAR signaling and demonstrate an
      approach for systematically engineering immune-cell responses to soluble,
      extracellular ligands.

PMID- 29377004
TI  - Antagonism of PPAR-gamma signaling expands human hematopoietic stem and
      progenitor cells by enhancing glycolysis.
AB  - Hematopoietic stem cells (HSCs) quiescently reside in bone marrow niches and have
      the capacity to self-renew or differentiate to form all of the blood cells
      throughout the lifespan of an animal. Allogeneic HSC transplantation is a life
      saving treatment for malignant and nonmalignant disorders. HSCs isolated from
      umbilical cord blood (CB) are used for hematopoietic cell transplantation (HCT),
      but due to the limited numbers of HSCs in single units of umbilical CB, a number
      of methods have been proposed for ex vivo expansion of human HSCs. We show here
      that antagonism of peroxisome proliferator-activated receptor (PPAR)-gamma
      promotes ex vivo expansion of phenotypically and functionally defined subsets of
      human CB HSCs and hematopoietic progenitor cells (HSPCs). PPAR-gamma antagonism
      in CB HSPCs strongly downregulated expression of several differentiation
      associated genes, as well as fructose-bisphosphatase 1 (FBP1; which encodes a
      negative regulator of glycolysis), and enhanced glycolysis without compromising
      mitochondrial metabolism. The expansion of CB HSPCs by PPAR-gamma antagonism was
      completely suppressed by removal of glucose or inhibition of glycolysis.
      Moreover, knockdown of FBP1 expression promoted glycolysis and ex vivo expansion
      of long-term repopulating CB HSPCs, whereas overexpression of FBP1 suppressed the
      expansion of CB HSPCs that was induced by PPAR-gamma antagonism. Our study
      suggests the possibility for a new and simple means for metabolic reprogramming
      of CB HSPCs to improve the efficacy of HCT.

PMID- 29377006
TI  - Traumatic brain injury: Minocycline reduces microglial activation but increases
      neurodegeneration after TBI.

PMID- 29377007
TI  - Neurodegenerative disease: Proteome points to synaptic dysfunction in dementia.

PMID- 29377009
TI  - Stroke: Kv1.3 inhibition shows therapeutic potential in animal models of
      ischaemic stroke.

PMID- 29377008
TI  - Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative
      disorders.
AB  - The blood-brain barrier (BBB) is a continuous endothelial membrane within brain
      microvessels that has sealed cell-to-cell contacts and is sheathed by mural
      vascular cells and perivascular astrocyte end-feet. The BBB protects neurons from
      factors present in the systemic circulation and maintains the highly regulated
      CNS internal milieu, which is required for proper synaptic and neuronal
      functioning. BBB disruption allows influx into the brain of neurotoxic blood
      derived debris, cells and microbial pathogens and is associated with inflammatory
      and immune responses, which can initiate multiple pathways of neurodegeneration.
      This Review discusses neuroimaging studies in the living human brain and post
      mortem tissue as well as biomarker studies demonstrating BBB breakdown in
      Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral
      sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic
      encephalopathy. The pathogenic mechanisms by which BBB breakdown leads to
      neuronal injury, synaptic dysfunction, loss of neuronal connectivity and
      neurodegeneration are described. The importance of a healthy BBB for therapeutic
      drug delivery and the adverse effects of disease-initiated, pathological BBB
      breakdown in relation to brain delivery of neuropharmaceuticals are briefly
      discussed. Finally, future directions, gaps in the field and opportunities to
      control the course of neurological diseases by targeting the BBB are presented.

PMID- 29377011
TI  - Neurological disorders of gait, balance and posture: a sign-based approach.
AB  - Neurological disorders of gait, balance and posture are both debilitating and
      common. Adequate recognition of these so-called disorders of axial mobility is
      important as they can offer useful clues to the underlying pathology in patients
      with an uncertain clinical diagnosis, such as those early in the course of
      neurological disorders. Medical teaching programmes typically take classic
      clinical presentations as the starting point and present students with a
      representative constellation of features that jointly characterize a particular
      axial motor syndrome. However, patients rarely present in this way to a physician
      in clinical practice. Particularly in the early stages of a disease, patients
      might display just one (or at best only a few) abnormal signs of gait, balance or
      posture. Importantly, these individual signs are never pathognomonic for any
      specific disorder but rather come with an associated differential diagnosis. In
      this Perspective, we offer a new diagnostic approach in which the presenting
      signs are taken as the starting point for a focused differential diagnosis and a
      tailored search into the underlying neurological syndrome.

PMID- 29377012
TI  - Widespread bacterial protein histidine phosphorylation revealed by mass
      spectrometry-based proteomics.
AB  - For decades, major difficulties in analyzing histidine phosphorylation have
      limited the study of phosphohistidine signaling. Here we report a method
      revealing widespread and abundant protein histidine phosphorylation in
      Escherichia coli. We generated an extensive E. coli phosphoproteome data set, in
      which a remarkably high percentage (~10%) of phosphorylation sites are
      phosphohistidine sites. This resource should help enable a better understanding
      of the biological function of histidine phosphorylation.

PMID- 29377013
TI  - Ab initio electron density determination directly from solution scattering data.
AB  - Using a novel iterative structure factor retrieval algorithm, here I show that
      electron density can be directly calculated from solution scattering data without
      modeling. The algorithm was validated with experimental data from 12 different
      biological macromolecules. This approach avoids many of the assumptions limiting
      the resolution and accuracy of modeling algorithms by explicitly calculating
      electron density. This algorithm can be applied to a wide variety of molecular
      systems.

PMID- 29377014
TI  - STED super-resolved microscopy.
AB  - Stimulated emission depletion (STED) microscopy provides subdiffraction
      resolution while preserving useful aspects of fluorescence microscopy, such as
      optical sectioning, and molecular specificity and sensitivity. However,
      sophisticated microscopy architectures and high illumination intensities have
      limited STED microscopy's widespread use in the past. Here we summarize the
      progress that is mitigating these problems and giving substantial momentum to
      STED microscopy applications. We discuss the future of this method in regard to
      spatiotemporal limits, live-cell imaging and combination with spectroscopy.
      Advances in these areas may elevate STED microscopy to a standard method for
      imaging in the life sciences.

PMID- 29377016
TI  - Acupuncture and low back pain.

PMID- 29377015
TI  - Vitamin A and retinoic acid combined have a more potent effect compared to
      vitamin A alone on the uptake of retinol into extrahepatic tissues of neonatal
      rats raised under vitamin A-marginal conditions.
AB  - Background: Vitamin A (VA, retinol) supplementation is widely used to reduce
      child mortality in low-income countries. However, existing research suggests that
      supplementation with VA alone may not be optimal for infants. Objective: We
      compared the effect of VA vs. VA combined with retinoic acid (VARA) on retinol
      uptake and turnover in organs of neonatal rats raised under VA-marginal
      conditions. Methods: Secondary analysis was conducted on data obtained from two
      prior kinetic studies of Sprague-Dawley neonatal rats nursed by mothers fed a VA
      marginal diet (0.35 mg retinol equivalents/kg diet). On postnatal d 4, pups had
      been treated with a single dose of VA (6 MUg/g; n = 52; VA study), VA + 10%
      retinoic acid (6 MUg/g; n = 42; VARA study) or placebo (canola oil; n = 94; both
      studies), all containing ~2 MUCi of [3H]retinol as the tracer for VA. Total
      retinol concentrations and tracer levels had been measured in plasma and tissues
      from 1 h to 14 d after dosing. Control group data from both studies were merged
      prior to analysis. Kinetic parameters were re-estimated and compared
      statistically. Results: VARA supplementation administered to neonatal rats within
      a few days after birth resulted in a lower turnover of retinol in the lungs,
      kidneys, and carcass and less frequent recycling of retinol between plasma and
      organs (100 vs. 288 times in VARA- vs. VA-treated group). Although the VA
      supplementation resulted in a higher concentration of retinol in the liver, VARA
      supplementation led to a higher uptake of postprandial retinyl esters into the
      lungs, intestines, and carcass. Conclusions: Given the relatively higher retinol
      uptake into several extrahepatic organs of neonates dosed orally with VARA, this
      form of supplementation may serve as a targeted treatment of low VA levels in the
      extrahepatic organs that continue to develop postnatally.

PMID- 29377010
TI  - Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and
      conundrums.
AB  - Considerable overlap has been identified in the risk factors, comorbidities and
      putative pathophysiological mechanisms of Alzheimer disease and related dementias
      (ADRDs) and type 2 diabetes mellitus (T2DM), two of the most pressing epidemics
      of our time. Much is known about the biology of each condition, but whether T2DM
      and ADRDs are parallel phenomena arising from coincidental roots in ageing or
      synergistic diseases linked by vicious pathophysiological cycles remains unclear.
      Insulin resistance is a core feature of T2DM and is emerging as a potentially
      important feature of ADRDs. Here, we review key observations and experimental
      data on insulin signalling in the brain, highlighting its actions in neurons and
      glia. In addition, we define the concept of 'brain insulin resistance' and review
      the growing, although still inconsistent, literature concerning cognitive
      impairment and neuropathological abnormalities in T2DM, obesity and insulin
      resistance. Lastly, we review evidence of intrinsic brain insulin resistance in
      ADRDs. By expanding our understanding of the overlapping mechanisms of these
      conditions, we hope to accelerate the rational development of preventive, disease
      modifying and symptomatic treatments for cognitive dysfunction in T2DM and ADRDs
      alike.

PMID- 29377017
TI  - Commentary: Effects of Video Game Training on Measures of Selective Attention and
      Working Memory in Older Adults: Results from a Randomized Controlled Trial.

PMID- 29377018
TI  - Retraction: Response of methane production via propionate oxidation to
      carboxylated multiwalled carbon nanotubes in paddy soil enrichments.
AB  - [This retracts the article DOI: 10.7717/peerj.4267.].

PMID- 29377019
TI  - Erratum: Correction of Acknowledgements.
AB  - [This corrects the article on p. 542 in vol. 60, PMID: 29184862.].

PMID- 29377020
TI  - Corrigendum: Ginsenoside Rb1 Enhances Atherosclerotic Plaque Stability by
      Improving Autophagy and Lipid Metabolism in Macrophage Foam Cells.
AB  - [This corrects the article on p. 727 in vol. 8, PMID: 29114222.].

PMID- 29377021
TI  - Surgical antimicrobial prophylaxis.

PMID- 29377022
TI  - Correction to: Management and investigation of a Serratia marcescens outbreak in
      a neonatal unit in Switzerland - the role of hand hygiene and whole genome
      sequencing.
AB  - [This corrects the article DOI: 10.1186/s13756-017-0285-x.].

PMID- 29377023
TI  - Stenting as a treatment for exercise-induced intracranial hypertension from
      bilateral jugular vein obstruction.

PMID- 29377024
TI  - Long-term registries: Answering tough questions with big data?

PMID- 29377026
TI  - Bridging crossroads to improve patient outcomes.

PMID- 29377025
TI  - Erratum to "Anti-Inflammatory Effect of 3-Bromo-4,5-Dihydroxybenzaldehyde, a
      Component of Polysiphonia morrowii, In Vivo and In Vitro" [Toxicol. Res. 33
      (2017) 325-332].
AB  - [This corrects the article on p. 325 in vol. 33, PMID: 29071017.].

PMID- 29377028
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1002/rmb2.12034.].

PMID- 29377027
TI  - Focusing on transitions of care: A change is here.
AB  - Transitions of care have emerged as an important point of vulnerability in the
      health care system where medical errors and clinical deterioration can occur.
      Most research in the area has focused on non-neurologically ill patients in the
      postdischarge transition from the inpatient to outpatient clinical environment in
      part due to the emergence of hospital readmissions reduction programs. A
      multidisciplinary strategy that addresses several common opportunities for
      improvement can mitigate the risk to patients during these periods and can serve
      as an opportunity for neurologists to take the lead in developing systems-based
      solutions that can ultimately enhance the quality of care for our patients.

PMID- 29377029
TI  - Antimicrobial prophylaxis for dental surgery.

PMID- 29377030
TI  - A practical guide to evaluating sleep disturbance in concussion patients.
AB  - Purpose of review: To provide an introduction and review of sleep metrics
      appropriate for use with an outpatient concussed population. Recent findings:
      Although sleep issues are frequently identified in concussion, sleep disturbance
      is rarely assessed in outpatient settings. Given that sleep disturbance may be
      indicative of, or contribute to, delayed neurocognitive recovery, measurement
      tools for sleep, rest, and activity behavior may be of both practical and
      research utility. Summary: Because sleep disturbance symptoms may vary between or
      within an individual throughout the course of recovery, it is recommended that
      sleep be measured at regular intervals over the entirety of recovery. Included is
      a discussion on how to select appropriate measures based on patient symptomology
      in addition to common practical concerns. Additional clinical considerations, a
      review of traditional pencil and paper methods of continuous sleep behavior
      monitoring, as well as technologies for measuring sleep and activity behavior are
      also included.

PMID- 29377031
TI  - Corrigendum: Much More than a Cardiotonic Steroid: Modulation of Inflammation by
      Ouabain.
AB  - [This corrects the article on p. 895 in vol. 8, PMID: 29176951.].

PMID- 29377032
TI  - Erratum Notice of Formatting Correction: In Vitro Cysteine Reactivates
      Organophosphate Insecticide Dichlorvos-Inhibited Human Cholinesterases.
AB  - [This corrects the article on p. E293 in vol. 17, PMID: 29062551.].

PMID- 29377033
TI  - Potential Mechanisms Underlying TGF-beta-mediated Complement Activation in Lung
      Fibrosis.
AB  - While our previous studies suggest that limiting bleomycin-induced complement
      activation suppresses TGF-beta signaling, the specific hierarchical interactions
      between TGF-beta and complement in lung fibrosis are unclear. Herein, we
      investigated the mechanisms underlying TGF-beta-induced complement activation in
      the pathogenesis of lung fibrosis. C57-BL6 mice were given intratracheal
      instillations of adenoviral vectors overexpressing TGF-beta (Ad-TGFbeta) or the
      firefly gene-luciferase (Ad-Luc; control). Two weeks later, mice with fibrotic
      lungs were instilled RNAi specific to receptors for C3a or C5a-C3ar or C5ar, and
      sacrificed at day 28. Histopathological analyses revealed that genetic silencing
      of C3ar or C5ar arrested the progression of TGF-beta-induced lung fibrosis,
      collagen deposition and content (hydroxyproline, col1a1/2); and significantly
      suppressed local complement activation. With genetic silencing of either C3ar or
      C5ar, in Ad-TGFbeta-injured lungs: we detected the recovery of Smad7 (TGF-beta
      inhibitor) and diminished local release of DAF (membrane-bound complement
      inhibitor); in vitro: TGF-beta-mediated loss of DAF was prevented. Conversely,
      blockade of the TGF-beta receptor prevented C3a-mediated loss of DAF in both
      normal primary human alveolar and small airway epithelial cells. Of the 52 miRNAs
      analyzed as part of the Affymetrix array, normal primary human SAECs exposed to
      C3a, C5a or TGF-beta caused discrete and overlapping miRNA regulation related to
      epithelial proliferation or apoptosis (miR-891A, miR-4442, miR-548, miR-4633),
      cellular contractility (miR-1197) and lung fibrosis (miR-21, miR-200C, miR-31HG,
      miR-503). Our studies present potential mechanisms by which TGF-beta activates
      complement and promotes lung fibrosis.

PMID- 29377034
TI  - Commentary: No unique effect of intergroup competition on cooperation: non
      competitive thresholds are as effective as competition between groups for
      increasing human cooperative behavior.

PMID- 29377035
TI  - The non-Huntington disease choreas: Five new things.
AB  - Purpose of review: Chorea can be due to a wide variety of causes. In this review,
      I provide updates on several recently identified genetic and autoimmune causes of
      chorea, and review evidence supporting the use of deep brain stimulation in
      chorea. Recent findings: New genes that may cause chorea include ADCY5 (encoding
      for adenylate cyclase 5) C9ORF72 (in addition to amyotrophic lateral sclerosis
      and frontotemporal dementia), and those responsible for the neurodegeneration
      with brain iron accumulation disorders. Novel autoantibodies are increasingly
      being identified as associated with a variety of neurologic syndromes, including
      chorea, in both paraneoplastic and non-paraneoplastic settings. Deep brain
      stimulation can be a useful intervention in patients with chorea who do not
      respond to oral medications, whether due to neurodegenerative or nondegenerative
      causes. Summary: New causes of chorea continue to be identified. Correct
      diagnosis is essential for prognostication and treatment.

PMID- 29377036
TI  - Social capital, collective action, and communal grazing lands in Uganda.
AB  - Recent scholars have found that collective action can be harnessed to sustainably
      manage common property, contrary to longstanding hypotheses that without
      effective external regulation community members will exploit communal resources.
      Researchers have also found that social capital, in addition to biophysical
      conditions and community attributes, is an important element of successful
      collective action. However, few studies exploring this topic have specifically
      examined communal grazing land, which is a critical component of rural
      livelihoods in many parts of the developing world. To address this gap, we
      explore the role that collective action plays in maintaining communal grazing
      lands through bridging, bonding, and linking social capital. In cases where the
      community does have communal grazing lands, we also explore the role of social
      capital in determining the condition of the land and the inclusiveness of access.
      Our analyses draw upon a community-level dataset composed of Uganda RePEAT survey
      data linked with high resolution gridded socio-environmental data. We observe
      that strong community bonds are associated with higher odds of successful
      collective action. However, increased links to external market forces may
      decrease the odds of successful collective action. These findings provide
      additional evidence for the complex relationship between social capital,
      collective action, and common property natural resource management.

PMID- 29377037
TI  - MRI pattern approach of adult-onset inherited leukoencephalopathies.

PMID- 29377039
TI  - Erratum: How neurologists are paid: Part 3: Hospital support, Veterans
      Administration, and neurohospitalists.
AB  - [This corrects the article on p. 412 in vol. 5, PMID: 26526185.].

PMID- 29377038
TI  - Corrigendum: Meclizine Prevents Ovariectomy-Induced Bone Loss and Inhibits
      Osteoclastogenesis Partially by Upregulating PXR.
AB  - [This corrects the article on p. 693 in vol. 8, PMID: 29046637.].

PMID- 29377040
TI  - Re: Neurology Research in Saudi Arabia: Urgent call for action.

PMID- 29377041
TI  - Use of a web portal among adult clinic patients seen for type 2 diabetes
      mellitus.
AB  - Background: To determine the number of adult clinic patients seen for type 2
      diabetes mellitus (T2DM) at an academic medical center and to examine
      characteristics of those who had or had not registered for a web portal. Methods:
      Electronic records were reviewed to identify web portal registration by patients
      treated for T2DM by age, sex, race and Hispanic ethnicity, and service (General
      Internal Medicine, Endocrinology). Results: A total of 1,401 patients with T2DM
      were seen in General Internal Medicine and Endocrinology outpatient clinics. Less
      than one third (32%) had registered for the web portal. Women were more likely to
      have registered for the web portal than men [odds ratio (OR) =1.25; 95% CI, 0.99
      1.57; P<0.063]. Black patients were less likely to have registered than whites
      (OR =0.40; 95% CI, 0.31-0.51; P<0.001). Patients who were 18-25 years of age were
      less likely to have registered for the web portal, along with those who were 56
      to 60 and >66 years of age. In multivariate analysis, a statistically significant
      association was observed between web portal registration and General Internal
      Medicine clinic vs. Endocrinology clinic (OR =2.96, P<0.001). Inverse
      associations were observed with age >18-25 years, male sex (adjusted OR =0.71,
      P=0.006), and Black race (OR =0.33, P<0.001). Conclusions: Additional research is
      needed to identify portal design features that improve glycemic control and
      interventions that will increase use of patient portals, especially among Black
      patients with T2DM and those with low health literacy or computer literacy.

PMID- 29377042
TI  - A superhydrophobic cone to facilitate the xenomonitoring of filarial parasites,
      malaria, and trypanosomes using mosquito excreta/feces.
AB  - Background: Molecular xenomonitoring (MX), the testing of insect vectors for the
      presence of human pathogens, has the potential to provide a non-invasive and cost
      effective method for monitoring the prevalence of disease within a community.
      Current MX methods require the capture and processing of large numbers of
      mosquitoes, particularly in areas of low endemicity, increasing the time, cost
      and labour required. Screening the excreta/feces (E/F) released from mosquitoes,
      rather than whole carcasses, improves the throughput by removing the need to
      discriminate vector species since non-vectors release ingested pathogens in E/F.
      It also enables larger numbers of mosquitoes to be processed per pool. However,
      this new screening approach requires a method of efficiently collecting E/F.
      Methods: We developed a cone with a superhydrophobic surface to allow for the
      efficient collection of E/F. Using mosquitoes exposed to either Plasmodium
      falciparum, Brugia malayi or Trypanosoma bruceibrucei, we tested the performance
      of the superhydrophobic cone alongside two other collection methods. Results: All
      collection methods enabled the detection of DNA from the three parasites. Using
      the superhydrophobic cone to deposit E/F into a small tube provided the highest
      number of positive samples (16 out of 18) and facilitated detection of parasite
      DNA in E/F from individual mosquitoes. Further tests showed that following a
      simple washing step, the cone can be reused multiple times, further improving its
      cost-effectiveness. Conclusions: Incorporating the superhydrophobic cone into
      mosquito traps or holding containers could provide a simple and efficient method
      for collecting E/F. Where this is not possible, swabbing the container or using
      the washing method facilitates the detection of the three parasites used in this
      study.

PMID- 29377043
TI  - Serum prolactin in seizure diagnosis: Glass half-full or half-empty?

PMID- 29377044
TI  - Diagnostic value of serum prolactin levels in PNES in the epilepsy monitoring
      unit.
AB  - Background: This is a retrospective study to determine the usefulness of serum
      prolactin levels in the epilepsy monitoring unit (EMU) for distinguishing
      psychogenic nonepileptic seizures (PNES) from epileptic seizures (ES). Methods:
      All the records of consecutive patients admitted to the EMU between 2008 and 2012
      were reviewed. Patients with a diagnosis of PNES and ES were selected. Serum
      prolactin level was obtained within 20 minutes for all patients, and an elevated
      prolactin level was defined as twice the patient's baseline value. A total of 607
      records were reviewed, and 389 patients were excluded because of incomplete
      information or lack of a clinical event. Results: A total of 218 patients were
      included in the analysis. A further 18 patients were excluded because of simple
      partial seizures or because the documented time of obtaining serum prolactin was
      not clear. A total of 146 patients had PNES, of which 42 had elevated prolactin
      levels, representing a 28.8% false-positive rate. All 22 patients with
      generalized tonic-clonic seizures had elevated serum prolactin; however, 5 of 32
      patients with complex partial seizures did not have an elevated prolactin level,
      representing a 15.6% false-negative rate. Conclusions: Serum prolactin levels do
      not provide any additional support for distinguishing PNES from ES. Furthermore,
      serum prolactin levels in this setting add unnecessary blood draws and financial
      burden for the patients. Therefore, prolactin levels should not be obtained
      routinely in the EMU. Classification of evidence: This study provides Class III
      evidence that postevent elevation of serum prolactin occurs in 84.4% of patients
      with ES and 28.8% of patients with PNES.

PMID- 29377045
TI  - Properties of hail storms over China and the United States from the Tropical
      Rainfall Measuring Mission.
AB  - A 16-yr record of hail reports over the south U.S. and from weather stations in
      China are collocated with Precipitation Features (PF) derived from the Tropical
      Rainfall Measuring Mission (TRMM) radar and passive microwave observations.
      Differences in the way hail is reported in the two nations make it difficult to
      draw meaningful conclusions about storm frequency. But taking the two together
      yields a wide spectrum of hail sizes, suitable for comparing with remote sensing
      measurements. While U.S. hail reports are dominated by cases with hail size
      greater than 19 mm, hail reports in China mostly include diameters of 1-10 mm and
      mostly occur over the Tibetan Plateau. The fraction of PFs collocated with hail
      reports (hail PFs) reaches 3% in the plains of the U.S. In China, the fraction is
      higher in high elevation regions than low elevation regions. Hail PFs (as
      reported in the U.S.) show lower brightness temperatures, higher lightning flash
      rates, stronger maximum reflectivity, and higher echo tops than those with
      smaller hail, as reported in China. The average near surface maximum reflectivity
      of hail PFs at high elevations (>= 2000 m) in China is about 5 dB smaller than
      those at low elevations. Larger hail is reported with PFs having stronger maximum
      reflectivity above 6 km, though the median of maximum reflectivity values at
      levels below 5 km is similar among the storms with large and small hail sizes.

PMID- 29377050
TI  - High-Pressure Water Injection Injuries of the Hand May Not Be Trivial.
AB  - High-pressure water injection injuries of the hand are uncommon, and there is
      limited literature to guide their treatment. The ideal management of these
      injuries, whether nonoperative with close observation or early surgical
      debridement, remains unknown. The authors retrospectively identified a cohort of
      patients with high-pressure water injection injuries to the hand during a 16-year
      period. Data collected included demographics, location of injection, hand
      dominance, type of treatment, need for additional surgery, and complications. The
      authors attempted to reach all patients by phone and email to assess long-term
      motion loss, sensation loss, and chronic pain. Nineteen patients met the
      inclusion criteria. The nondominant hand was involved in 84% and the index finger
      in nearly half. Two of 10 patients in the early surgery group required additional
      procedures, including a trigger finger release and serial debridements for
      Pseudomonas infection. Three of 9 patients without early debridement eventually
      required surgery, including debridement of a septic flexor tenosynovitis,
      fingertip amputation, and metacarpophalangeal disarticulation. Sixteen percent of
      patients developed infection, and 1 patient developed compartment syndrome. This
      is the largest reported cohort of both operatively and nonoperatively treated
      high-pressure water injection injuries to the hand. This is the first report of
      amputation as a complication. Infection and delayed presentation portend a poor
      outcome. Complications may arise even after early surgical debridement, and long
      term sequelae are common. These injuries are not inherently benign and warrant
      immediate medical attention, early antibiotics, and a low threshold for close
      observation or surgical debridement. [Orthopedics. 2018; 41(2):e245-e251.].

PMID- 29377051
TI  - Scientific Misconduct (Fraud) in Medical Writing.
AB  - Scientific misconduct (fraud) in medical writing is an important and not
      infrequent problem for the scientific community. Although noteworthy examples of
      fraud surface occasionally in the media, detection of fraud in medical publishing
      is generally not as straightforward as one might think. National bodies on ethics
      in science, strict selection criteria, a robust peer-review process, careful
      statistical validation, and anti-plagiarism and image-fraud detection software
      contribute to the production of high-quality manuscripts. This article reviews
      the various types of fraud in medical writing, discusses the related literature,
      and describes tools journals implement to unmask fraud. [Orthopedics. 2018;
      41(2):e176-e183].

PMID- 29377052
TI  - Long-term Outcomes of Partial Trapeziectomy With Capsular Interposition
      Arthroplasty for Osteoarthritis of the Thumb Basal Joint.
AB  - The purpose of this study was to describe long-term outcomes of partial
      trapeziectomy with capsular interposition (PTCI) arthroplasty for patients with
      osteoarthritis of the basal joint of the thumb. A total of 27 patients (20 women,
      7 men; 32 thumbs) with a mean age of 61 years (range, 47-74 years) agreed to
      return for follow-up and were included in the study. Mean postoperative follow-up
      was 64.3 months (range, 28-112 months). Evaluation included tests for grip and
      pinch strength; range of motion of the metacarpophalangeal joint; measurement of
      the first web space; completion of the Disabilities of the Arm, Shoulder and Hand
      (DASH) questionnaire; visual analog scale (VAS) measurements; and radiographic
      examination of the hand. A paired, 2-tailed t test was used to determine
      statistical significance (P<.05) of pre- and postoperative values. Postoperative
      values for grip strength were significantly increased from preoperative values.
      No significant loss of pinch strength was noted. Excessive hyperextension of the
      metacarpophalangeal joint did not occur, and the first web space was maintained.
      The mean DASH questionnaire and VAS scores were 5.06 (range, 0-26.5) and 0.32,
      respectively. Use of PTCI arthroplasty resulted in minimal loss in thumb height
      (7%) and significantly reduced thumb metacarpal subluxation (13%). There were no
      reported complications. The low DASH questionnaire and VAS scores compare well
      with other studies and indicate good functional outcomes. In treating thumb basal
      joint osteoarthritis, use of PTCI arthroplasty may result in improved thumb
      stability and grip strength, minimal subsidence of the thumb metacarpal, and
      reduced joint subluxation. [Orthopedics. 2018; 41(2):e228-e233.].

PMID- 29377053
TI  - Factors Associated With Failure of Hip Arthroscopy in Patients With Hip
      Dysplasia.
AB  - The purpose of this study was to compare a group of dysplastic hips treated
      successfully with hip arthroscopy with a group of dysplastic hips treated
      unsuccessfully with hip arthroscopy to determine (1) preoperative patient
      characteristics and radiographic parameters and (2) intraoperative findings and
      treatment associated with outcome. The authors retrospectively reviewed a
      prospective database of 20 adult patients (17 female, 3 male) with hip dysplasia
      who underwent primary hip arthroscopy between January 2009 and February 2013.
      Modified Beck scores to quantify cartilage damage as well as preoperative and
      postoperative radiographic measurements (including alpha, Tonnis, and lateral
      center edge angles [LCEAs]) were compared between patients who failed hip
      arthroscopy (11 patients) and those who did not (9 patients). Failure after hip
      arthroscopy was defined as a modified Harris hip score of less than 80 or the
      need for subsequent hip arthroscopy, arthroplasty, or periacetabular osteotomy.
      The mean follow-up for the successful patients was 58 months (range, 37-82
      months), with an average modified Harris hip score of 93 at most recent follow
      up. Preoperative radiographs showed a lower mean LCEA (18.0 degrees  vs 21.3
      degrees ; P=.02) in the failure group, and all successes occurred with a LCEA of
      17 degrees  or greater. The failure group was more likely to have rim resection
      of greater than 3 mm performed (hazard ratio, 3.53; P=.04). Among the hips with
      dysplasia undergoing arthroscopic treatment, patients with a poor outcome were
      more likely to have an LCEA of less than 17 degrees  and intraoperative rim
      resection of greater than 3 mm. Furthermore, the labral repair group did
      substantially better than the labral debridement group. [Orthopedics. 2018;
      41(2):e234-e239.].

PMID- 29377054
TI  - Mechanical Testing of Epiphysiodesis Screws.
AB  - Epiphysiodesis is performed to treat leg-length discrepancies and angular
      deformities in children. However, when placed across a physis to modulate growth,
      screws can bend or break postoperatively. This study evaluated the mechanical
      properties of 3 different screw designs commonly used when performing an
      epiphysiodesis. Six 4.0-mm cannulated, fully threaded; six 4.0-mm cannulated,
      partially threaded; and six 4.0-mm noncannulated, partially threaded cancellous
      screws underwent cantilever bending and tension testing in a simulated physis.
      All screws were tested in simulated cancellous bone foam blocks. All testing was
      performed using a servo-hydraulic testing machine to determine stiffness and
      ultimate load. For statistical analysis, one-way analysis of variance with
      Tukey's honestly significant difference test in post hoc analysis was used to
      assess significant differences among groups (P<.05). The noncannulated, partially
      threaded screws had a significantly lower stiffness than the 2 cannulated screw
      types in the tension test (P<.001) and bending test (P<.001). Additionally, the
      noncannulated, partially threaded screws had significantly higher ultimate load
      to failure than the 2 cannulated screw types in the tension test (P<.001) and the
      cannulated, partially threaded screws in the bending test (P=.045). The results
      indicate that noncannulated, partially threaded screws have a higher ultimate
      load capacity and are less stiff than both cannulated, partially threaded screws
      and cannulated, fully threaded screws. Surgeons should take into consideration
      that noncannulated, partially threaded screws are less likely to fail following
      epiphysiodesis. [Orthopedics. 2018; 41(2):e240-e244.].

PMID- 29377055
TI  - Outcomes of Cementless Total Knee Arthroplasty in Patients With Rheumatoid
      Arthritis.
AB  - The objective of this study was to evaluate implant survivorship, clinical
      outcomes, postoperative complications, and radiographic outcomes of cementless
      total knee arthroplasty (TKA) in patients who have rheumatoid arthritis (RA).
      Patients who underwent a primary cementless posterior-stabilized TKA and who had
      RA were reviewed. A total of 126 TKAs in 122 patients who had a mean follow-up of
      4 years were analyzed. Implant survivorship was calculated. Postoperative
      clinical and radiographic follow-up was performed at approximately 6 weeks and 3
      months and then annually. Changes in range of motion and Knee Society scores were
      noted. Radiographic evaluation was conducted as part of the follow-up process.
      Implant survivorship was 99.2%, with 1 aseptic failure. At final follow-up, mean
      extension and flexion were 2 degrees  (range, 0 degrees -10 degrees ) and 124
      degrees  (range, 95 degrees -140 degrees ), respectively. Mean Knee Society pain
      and function scores were 92 points (range, 80-100 points) and 84 points (range,
      70-90 points), respectively. There were no surgical complications. No progressive
      radiolucencies, loosening, or subsidence were noted except from the single
      aseptic failure reported. This study reports excellent survivorship and clinical
      and radiographic outcomes of cementless TKAs in RA patients. Although the
      decision regarding whether to use cemented or cementless TKAs in these patients
      should be based on surgeon experience and patient characteristics, the recent
      advances in implant fixation of cementless TKAs indicate no salient
      contraindications for RA patients. [Orthopedics. 2018; 41(2):103-106.].

PMID- 29377056
TI  - Determination of the maximum tolerated dose of intranasal sufentanil and
      midazolam in Chinese: a pilot study.
AB  - BACKGROUND: The purpose of this study was to determine the maximum tolerated dose
      (MTD, the dose of causing 10% respiratory depression) of intranasal sufentanil
      (SUF) and midazolam (MID) for sedation during gastroscopy by continual
      reassessment method (CRM). METHODS: Patients (18-65 years old) scheduled for
      gastroscopy were recruited in this study. Subjects received intranasal SUF and
      MID for sedation. The dose of MID (5 mg) was fixed, while the dose of SUF was
      increased progressively (six incremental doses ranging from 0-0.60 MUg/kg, n = 3
      for each dose). The first cohort received a conservative, predetermined dose of 5
      mg MID and 0 MUg/kg SUF, subsequent cohorts received doses of SUF that were
      determined by the responses of all previous patients using Bayesian-based
      software. The dose allocated to the next cohort is the one with an updated
      posterior response probability closest to 10%. RESULTS: Thirty Chinese patients
      scheduled for gastroscopy were included. Probability of respiratory depression at
      each dose was as follows: 5 mg MID + 0 MUg/kg SUF, 0.4%; 5 mg MID + 0.1 MUg/kg
      SUF, 0.8%; 5 mg MID + 0.2 MUg/kg SUF, 1.8%; 5 mg MID + 0.3 MUg/kg SUF, 3.7%; 5 mg
      MID + 0.4 MUg/kg SUF, 9.9%; 5 mg MID + 0.5 MUg/kg SUF, 17.8%; 5 mg MID + 0.6
      MUg/kg SUF, 36.0%. CONCLUSION: The MTD of intranasal MID and SUF for sedation
      during gastroscopy causing 10% respiratory depression is 5 mg MID + 0.4 MUg/kg
      SUF, based on CRM.

PMID- 29377057
TI  - Digital Therapeutics: An Integral Component of Digital Innovation in Drug
      Development.
AB  - Digital therapeutics represent a new treatment modality in which digital systems
      such as smartphone apps are used as regulatory-approved, prescribed therapeutic
      interventions to treat medical conditions. In this article we provide a critical
      overview of the rationale for investing in such novel modalities, including the
      unmet medical needs addressed by digital therapeutics and the potential for
      reducing current costs of medical care. We also discuss emerging pathways to
      regulatory approval and how innovative business models are enabling further
      growth in the development of digital therapeutics. We conclude by providing some
      recent examples of digital therapeutics that have gained regulatory approval and
      highlight opportunities for the near future.

PMID- 29377058
TI  - A simplified guide to randomized controlled trials.
AB  - A randomized controlled trial is a prospective, comparative, quantitative
      study/experiment performed under controlled conditions with random allocation of
      interventions to comparison groups. The randomized controlled trial is the most
      rigorous and robust research method of determining whether a cause-effect
      relation exists between an intervention and an outcome. High-quality evidence can
      be generated by performing an randomized controlled trial when evaluating the
      effectiveness and safety of an intervention. Furthermore, randomized controlled
      trials yield themselves well to systematic review and meta-analysis providing a
      solid base for synthesizing evidence generated by such studies. Evidence-based
      clinical practice improves patient outcomes and safety, and is generally cost
      effective. Therefore, randomized controlled trials are becoming increasingly
      popular in all areas of clinical medicine including perinatology. However,
      designing and conducting an randomized controlled trial, analyzing data,
      interpreting findings and disseminating results can be challenging as there are
      several practicalities to be considered. In this review, we provide simple
      descriptive guidance on planning, conducting, analyzing and reporting randomized
      controlled trials.

PMID- 29377059
TI  - Decoding diagnosis and lifetime consumption in alcohol dependence from grey
      matter pattern information.
AB  - OBJECTIVE: We investigated the potential of computer-based models to decode
      diagnosis and lifetime consumption in alcohol dependence (AD) from grey-matter
      pattern information. As machine-learning approaches to psychiatric neuroimaging
      have recently come under scrutiny due to unclear generalization and the opacity
      of algorithms, our investigation aimed to address a number of methodological
      criticisms. METHOD: Participants were adult individuals diagnosed with AD (N =
      119) and substance-naive controls (N = 97) ages 20-65 who underwent structural
      MRI. Machine-learning models were applied to predict diagnosis and lifetime
      alcohol consumption. RESULTS: A classification scheme based on regional grey
      matter attained 74% diagnostic accuracy and predicted lifetime consumption with
      high accuracy (r = 0.56, P < 10-10 ). A key advantage of the classification
      scheme was its algorithmic transparency, revealing cingulate, insular and
      inferior frontal cortices as important brain areas underlying classification.
      Validation of the classification scheme on data of an independent trial was
      successful with nearly identical accuracy, addressing the concern of
      generalization. Finally, compared to a blinded radiologist, computer-based
      classification showed higher accuracy and sensitivity, reduced age and gender
      biases, but lower specificity. CONCLUSION: Computer-based models applied to whole
      brain grey-matter predicted diagnosis and lifetime consumption in AD with good
      accuracy. Computer-based classification may be particularly suited as a screening
      tool with high sensitivity.

PMID- 29377060
TI  - Battles Worth Fighting.

PMID- 29377061
TI  - Individualized lung recruitment maneuver guided by pulse-oximetry in anesthetized
      patients undergoing laparoscopy: a feasibility study.
AB  - BACKGROUND: We conducted this study to test whether pulse-oximetry hemoglobin
      saturation (SpO2 ) can personalize the implementation of an open-lung approach
      during laparoscopy. Thirty patients with SpO2  >= 97% on room-air before
      anesthesia were studied. After anesthesia and capnoperitoneum the FIO2 was
      reduced to 0.21. Those patients whose SpO2 decreased below 97% - an indication of
      shunt related to atelectasis - completed the following phases: (1) First
      recruitment maneuver (RM), until reaching lung's opening pressure, defined as the
      inspiratory pressure level yielding a SpO2 >= 97%; (2) decremental positive end
      expiratory (PEEP) titration trial until reaching lung's closing pressure defined
      as the PEEP level yielding a SpO2  < 97%; (3) second RM and, (4) ongoing
      ventilation with PEEP adjusted above the detected closing pressure. RESULTS: When
      breathing air, in 24 of 30 patients SpO2 was < 97%, PaO2 /FIO2  ? 53.3 kPa and
      negative end-expiratory transpulmonary pressure (PTP-EE ). The mean (SD) opening
      pressures were found at 40 (5) and 33 (4) cmH2 O during the first and second RM,
      respectively (P < 0.001; 95% CI: 3.2-7.7). The closing pressure was found at 11
      (5) cmH2 O. This SpO2 -guided approach increased PTP-EE (from -6.4 to 1.2 cmH2 O,
      P < 0.001) and PaO2 /FIO2 (from 30.3 to 58.1 kPa, P < 0.001) while decreased
      driving pressure (from 18 to 10 cmH2 O, P < 0.001). SpO2 discriminated the lung's
      opening and closing pressures with accuracy taking the reference parameter PTP-EE
      (area under the receiver-operating-curve of 0.89, 95% CI: 0.80-0.99). CONCLUSION:
      The non-invasive SpO2 monitoring can help to individualize an open-lung approach,
      including all involved steps, from the identification of those patients who can
      benefit from recruitment, the identification of opening and closing pressures to
      the subsequent monitoring of an open-lung condition.

PMID- 29377062
TI  - Adverse effects of anti-epileptics in trigeminal neuralgiform pain.
AB  - BACKGROUND: Side effects of anti-epileptic drugs (AEDs) have not been adequately
      documented in trigeminal neuralgia and its variants. The aim of this
      observational cross-sectional study was to compare the A-B Neuropsychological
      Assessment Schedule (ABNAS), which measures cognitive side effects to the Adverse
      Events Profile (AEP), which looks at a broader range of side effects, and to
      investigate drug/dosage relationships with questionnaire scores to help determine
      a point at which a drug change would be indicated. METHODS: One hundred five
      patients were recruited from a facial pain clinic, over a 10-month period. Self
      complete questionnaire scores were compared between patients using different
      AEDs. RESULTS: A-B Neuropsychological Assessment Schedule score correlated well
      with AEP indicating that cognitive side effects were a significant burden. Toxic
      range on the ABNAS was estimated to occur when scores were >43/72 (95% CI: 37.4
      48.6). Polytherapy is weakly associated with the higher scores. Oxcarbazepine
      dosage was found to linearly correlate with AEP and ABNAS scores, better than
      carbamazepine dosage. Memory alteration was least common with lamotrigine and
      oxcarbazepine, and there was less association between fatigues with
      oxcarbazepine/pregabalin. CONCLUSION: Anti-epileptic drugs have significant side
      effects. The ABNAS questionnaire is a useful tool along with the AEP to recognize
      and monitor AEDs' side effects and to help to adjust medications to optimal
      dosage.

PMID- 29377063
TI  - Measurement of Typhi Vi antibodies can be used to assess adaptive immunity in
      patients with immunodeficiency.
AB  - Vaccine-specific antibody responses are essential in the diagnosis of antibody
      deficiencies. Responses to Pneumovax II are used to assess the response to
      polysaccharide antigens, but interpretation may be complicated. Typhim Vi(r) , a
      polysaccharide vaccine for Salmonella typhoid fever, may be an additional option
      for assessing humoral responses in patients suspected of having an
      immunodeficiency. Here we report a UK multi-centre study describing the
      analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme
      linked immunosorbent assay (ELISA) calibrated to an affinity-purified Typhi Vi
      IgG preparation. Intra- and interassay imprecision was low and the assay was
      linear, between 7.4 and 574 U/ml (slope = 0.99-1.00; R2  > 0.99); 71% of blood
      donors had undetectable Typhi Vi IgG antibody concentrations. Of those with
      antibody concentrations  > 7.4 U/ml, the concentration range was 7.7-167 U/ml. In
      antibody-deficient patients receiving antibody replacement therapy the median
      Typhi Vi IgG antibody concentrations were  < 25 U/ml. In vaccinated normal
      healthy volunteers, the median concentration post-vaccination was 107 U/ml (range
      31-542 U/ml). Eight of eight patients (100%) had post-vaccination concentration
      increases of at least threefold and six of eight (75%) of at least 10-fold. In an
      antibody-deficient population (n = 23), only 30% had post-vaccination
      concentration increases of at least threefold and 10% of at least 10-fold. The
      antibody responses to Pneumovax II and Typhim Vi(r) correlated. We conclude that
      IgG responses to Typhim Vi(r) vaccination can be measured using the VaccZyme
      Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a
      useful additional test to accompany Pneumovax II responses for the assessment of
      antibody deficiencies.

PMID- 29377065
TI  - The effects of added whey protein to a pre-operative carbohydrate drink on
      glucose and insulin response.
AB  - BACKGROUND: Pre-operative complex carbohydrate (CHO) drinks are recommended to
      attenuate post-operative insulin resistance. However, many institutions use
      simple CHO drinks, which while convenient, may have less metabolic effects. Whey
      protein may enhance insulin release when added to complex CHO. The aim of this
      study was to compare the insulin response to simple CHO vs. simple CHO
      supplemented with whey protein. METHODS: Twelve healthy volunteers participated
      in this double-blinded, within subject, cross-over design study investigating
      insulin response to simple CHO drink vs. simple CHO + whey (CHO + W) drink. The
      primary outcome was the accumulated insulin response during 180 min after
      ingestion of the drinks (Area under the curve, AUC). Secondary outcomes included
      plasma glucose and ghrelin levels, and gastric emptying rate estimated by
      acetaminophen absorption technique. Data presented as mean (SD). RESULTS: There
      was no differences in accumulated insulin response after the CHO or CHO + W
      drinks [AUC: 15 (8) vs. 20 (14) nmol/l, P = 0.27]. Insulin and glucose levels
      peaked between 30 and 60 min and reached 215 (95) pmol/l and 7 (1) mmol/l after
      the CHO drink and to 264 (232) pmol/l and 6.5 (1) mmol/l after the CHO + W drink.
      There were no differences in glucose or ghrelin levels or gastric emptying with
      the addition of whey. CONCLUSION: The addition of whey protein to a simple CHO
      drink did not change the insulin response in healthy individuals. The peak
      insulin responses to simple CHO with or without whey protein were lower than that
      previously reported with complex CHO drinks. The impact of simple carbohydrate
      drinks with lower insulin response on peri-operative insulin sensitivity requires
      further study.

PMID- 29377066
TI  - A triple-blind, placebo-controlled randomised trial of the ilioinguinal
      transversus abdominis plane (I-TAP) nerve block for elective caesarean section.
AB  - This study investigated the efficacy of a new ilioinguinal-transversus abdominis
      plane block when used as a component of multimodal analgesia. We conducted a
      prospective, triple-blind, placebo-controlled randomised study of 100 women
      undergoing elective caesarean section. All women had spinal anaesthesia with
      hyperbaric bupivacaine, 15 MUg fentanyl and 150 MUg morphine, as well as 100 mg
      diclofenac and 1.5 g paracetamol rectally. Women were randomly allocated to
      receive the ilioinguinal-transversus abdominis plane block or a sham block at the
      end of surgery. The primary outcome was the difference in fentanyl patient
      controlled analgesia dose at 24 h. Secondary outcomes included postoperative pain
      scores, adverse effects and maternal satisfaction. The cumulative mean (95%CI)
      fentanyl dose at 24 h was 71.9 (55.6-92.7) MUg in the ilioinguinal-transversus
      abdominis group compared with 179.1 (138.5-231.4) MUg in the control group (p <
      0.001). Visual analogue scale pain scores averaged across time-points were 1.9
      (1.5-2.3) mm vs. 5.0 (4.3-5.9) mm (p = 0.006) at rest, and 4.7 (4.1-5.5) mm vs.
      11.3 (9.9-13.0) mm (p = 0.001) on movement, respectively. Post-hoc analysis
      showed that the ilioinguinal-transversus abdominis group was less likely to use
      >= 1000 MUg fentanyl compared with the control group (2% vs. 16%; p = 0.016).
      There were no differences in opioid-related side-effects or maternal satisfaction
      with analgesia. The addition of the ilioinguinal-transversus abdominis plane
      block provides superior analgesia to our usual multimodal analgesic regimen.

PMID- 29377064
TI  - Benefit of Preemptive Pharmacogenetic Information on Clinical Outcome.
AB  - The development of new knowledge around the genetic determinants of variable drug
      action has naturally raised the question of how this new knowledge can be used to
      improve the outcome of drug therapy. Two broad approaches have been taken: a
      point-of-care approach in which genotyping for specific variant(s) is undertaken
      at the time of drug prescription, and a preemptive approach in which multiple
      genetic variants are typed in an individual patient and the information archived
      for later use when a drug with a "pharmacogenetic story" is prescribed. This
      review addresses the current state of implementation, the rationale for these
      approaches, and barriers that must be overcome. Benefits to pharmacogenetic
      testing are only now being defined and will be discussed.

PMID- 29377067
TI  - Bone marrow biopsies not indicated for response assessment in follicular lymphoma
      trials regardless of type of imaging study - Response to Adams and Kwee.

PMID- 29377068
TI  - Dissection of a circulating CD3+ CD20+ T cell subpopulation in patients with
      psoriasis.
AB  - CD3+ CD20+ T cells are a population of CD3+ T cells that express CD20 and
      identified in healthy donors and autoimmune diseases. However, the nature and
      role of these cells in patients with psoriasis remain unclear. In this study, we
      aimed to investigate the level, phenotype, functional and clinical relevance of
      CD3+ CD20+ T cells in the peripheral blood of patients with psoriasis. We found
      that a small subset of CD3+ T cells expressed CD20 molecule in the peripheral
      blood of patients with psoriasis, and their levels were similar to those in
      healthy donors. Circulating CD3+ CD20+ T cells in patients with psoriasis were
      enriched in CD4+ cells and displayed an activated effector phenotype, as these
      cells contained fewer CD45RA+ -naive and CCR7+ cells with increased activity than
      those of CD3+ T cells lacking CD20. In addition, compared with healthy donors,
      circulating CD3+ CD20+ T cells in patients with psoriasis produced more
      cytokines, interleukin (IL)-17A, tumour necrosis factor (TNF)-alpha and IL-21,
      but not IL-4 and IFN-gamma. Furthermore, a significantly positive correlation was
      found between the levels of IL-17A, TNF-alpha and IL-21-production CD3+ CD20+ T
      cells with Psoriasis Area and Severity Index scores. Our findings suggest that
      CD3+ CD20+ T cells may play a role in the pathogenesis of psoriasis.

PMID- 29377069
TI  - Megakaryocytes harbour the del(5q) abnormality despite complete clinical and
      cytogenetic remission induced by lenalidomide treatment.
AB  - The mechanisms underlying lenalidomide-resistance of del(5q) MDS stem cells
      remain to be elucidated and may include cell-intrinsic as well as
      microenvironmental causes. Abnormal hypolobated megakaryocytes constitute one of
      the hallmarks of del(5q) MDS. We hypothesized that these cells have potential
      implications for the regulation of haematopoietic stem cells (HSC) similarly to
      what has recently been described for megakaryocytes in the murine system.
      Therefore, we conducted a study to determine the response of abnormal hypolobated
      megakaryocytes to lenalidomide therapy. We studied lenalidomide-treated patients
      in the MDS-004 trial as well as a cohort seen at our institution. Morphological
      evaluation at time of complete cytogenetic remission (CCyR) demonstrated the
      persistence of hypolobated megakaryocytes in all evaluable patients (n = 9).
      Furthermore, we provide evidence that the abnormal hypolobated morphology is
      restricted to del(5q) megakaryocytes, both at diagnosis and during CCyR. Using
      fluorescence in situ hybridisation analysis on flow-sorted stem- and progenitor
      populations, we observed a similar degree of clonal involvement in megakaryocyte
      erythroid-progenitors as in HSC. Taken together, our findings suggest that
      megakaryocyte morphology might aid in the evaluation of patients where
      discontinuation of lenalidomide is considered and offers interesting hypotheses
      for further investigation of lenalidomide resistance.

PMID- 29377070
TI  - Factors influencing risk-based care of the childhood cancer survivor in the 21st
      century.
AB  - The population of adult survivors of childhood cancer continues to grow as
      survival rates improve. Although it is well established that these survivors
      experience various complications and comorbidities related to their malignancy
      and treatment, this risk is modified by many factors that are not directly linked
      to their cancer history. Research evaluating the influence of patient-specific
      demographic and genetic factors, premorbid and comorbid conditions, health
      behaviors, and aging has identified additional risk factors that influence cancer
      treatment-related toxicity and possible targets for intervention in this
      population. Furthermore, although current long-term follow-up guidelines
      comprehensively address specific therapy-related risks and provide screening
      recommendations, the risk profile of the population continues to evolve with
      ongoing modification of treatment strategies and the emergence of novel
      therapeutics. To address the multifactorial modifiers of cancer treatment-related
      health risk and evolving treatment approaches, a patient-centered and risk
      adapted approach to care that often requires a multidisciplinary team approach,
      including medical and behavioral providers, is necessary for this population. CA
      Cancer J Clin 2018;68:133-152. (c) 2018 American Cancer Society.

PMID- 29377071
TI  - How I manage red cell transfusions in patients with sickle cell disease.
AB  - Sickle cell disease is one of the commonest serious inherited diseases in the
      world, and red cell transfusion is still one of the few effective treatments for
      acute and chronic complications. Transfusion corrects anaemia and dilutes out the
      number of red cells able to cause vaso-occlusion and vascular damage. Urgent red
      cell transfusions are used to correct acute anaemia, treat acute chest syndrome
      and patients with acute neurological symptoms. We use elective transfusions
      preoperatively for moderate risk surgery, and in some pregnant women. There is
      good evidence for the use of long-term regular transfusions in primary stroke
      prevention, with the aim of keeping the percentage of sickle haemoglobin below
      30%. Long-term transfusions are also used in secondary stroke prevention, and the
      management of progressive organ damage, including renal impairment and pulmonary
      hypertension. Blood needs to be matched for ABO, RH and Kell, although
      alloantibodies may still develop and require more careful, extended cross
      matching. Delayed haemolytic transfusion reactions are relatively common,
      difficult to diagnose and manage, and potentially fatal.

PMID- 29377072
TI  - The effect of interleukin-8 truncations on its interactions with
      glycosaminoglycans.
AB  - The chemokine interleukin-8 (IL-8, CXCL8) plays an important role in inflammatory
      processes and consecutive wound healing. It recruits primarily neutrophils to
      infection sites and stimulates their degranulation and phagocytosis in effector
      cells. IL-8 binds glycosaminoglycans (GAGs), a class of complex linear anionic
      polysaccharides often organized into diversely sulfated micro-domains, that
      enriches the protein concentration locally and so facilitate the formation of
      stable concentration gradients. In this study, we applied experimental and
      computational techniques to investigate the binding of wild type and truncated IL
      8 variants to natural and chemically modified GAGs to gain further insight into
      the IL-8/GAG interaction. Circular dichroism spectroscopy of IL-8 variants did
      not reveal major structural changes upon GAG binding. Heparin affinity
      chromatography clearly demonstrates that gradual truncation of the C-terminal
      helix leads to decreasing affinities. Similarly, surface plasmon resonance
      indicates participation of both IL-8 termini in GAG binding, which strength is
      dependent on GAG sulfation degree. Molecular modeling suggests that C-terminal
      truncation of IL-8 weakens the interaction with GAGs by an alteration of IL-8 GAG
      binding site. Our study provides more detailed understanding of the IL-8/GAG
      interaction and contributes to the data of potential use for the development of
      biomedical implications in tissue regeneration.

PMID- 29377073
TI  - No difference in ultraviolet B-induced changes in antigen-presenting cells and
      cytokines between patients with and without loss-of-function mutations in FLG.

PMID- 29377074
TI  - A case of facial burn due to the misuse of garlic face mask for acne.

PMID- 29377075
TI  - Factors Associated With Postmarketing Research for Approved Indications for Novel
      Medicines Approved by Both the FDA and EMA Between 2005 and 2010: A Multivariable
      Analysis.
AB  - We examined whether drug-related characteristics-conditions, development,
      manufacturers, revenues-were associated with postmarketing research in terms of
      the number of trials and total population to be enrolled. We included 63 drugs,
      corresponding to 3,867 postmarketing trials of approved indications. On
      multivariable analysis, both the number of postmarketing trials and population to
      be enrolled were associated with expected length of treatment (ratio of means
      (RoM) = 2.35 and RoM = 8.65) and number of patients in pivotal trials (RoM = 1.11
      and RoM = 1.25 per thousand patients). The number of postmarketing trials was
      increased for drugs approved with surrogate endpoints (RoM = 2.19), generating
      high revenues (RoM = 1.08 per billion dollars) and addressing greater disease
      burden (RoM = 1.90 per hundred million disability-adjusted life years). The
      population to be included was increased for drugs approved after an increased
      number of pivotal trials (RoM = 1.82) and those unaffected by safety concerns
      (RoM = 2.63). Postmarketing trials seem to be driven both by medical and market
      factors.

PMID- 29377076
TI  - The CDK inhibitor purvalanol A induces neutrophil apoptosis and increases the
      turnover rate of Mcl-1: potential role of p38-MAPK in regulation of Mcl-1
      turnover.
AB  - Human neutrophils are terminally differentiated cells that do not replicate and
      yet express a number of enzymes, notably cell cycle-dependent kinases (CDKs),
      that are associated normally with control of DNA synthesis and cell cycle
      progression. In neutrophils, CDKs appear to function mainly to regulate
      apoptosis, although the mechanisms by which they regulate this process are
      largely unknown. Here we show that the CDK2 inhibitor, purvalanol A, induces a
      rapid decrease in myeloid cell leukaemia factor-1 (Mcl-1) levels in human
      neutrophils and peripheral blood mononuclear cells (PBMCs), but only induces
      apoptosis in neutrophils which are dependent upon expression on this protein for
      survival. This rapid decrease in cellular Mcl-1 protein levels was due to a
      purvalanol A-induced decrease in stability, with the half-life of the protein
      decreasing from approximately 2 h in control cells to just over 1 h after
      addition of the CDK2 inhibitor: it also blocked the granulocyte-macrophage colony
      stimulating factor (GM-CSF)-dependent stabilization of Mcl-1. Purvanalol A
      blocked GM-CSF-stimulated activation of extracellular-regulated kinase (Erk) and
      signal transducer and activator of transcription (STAT)-3, and stimulated an
      additive activation of protein kinase B (Akt) with GM-CSF. Purvalanol A alone
      stimulated a rapid and sustained activation of p38-mitogen-activated protein
      kinase (MAPK) and the pan p38-MAPK inhibitor, BIRB796, partly blocked the
      purvalanol A-induced apoptosis and Mcl-1 loss. These novel effects of purvalanol
      A may result, at least in part, from blocking GM-CSF-mediated Erk activation. In
      addition, we propose that purvalanol A-induced activation of p38-MAPK is, at
      least in part, responsible for its rapid effects on Mcl-1 turnover and
      acceleration of neutrophil apoptosis.

PMID- 29377077
TI  - Population PK and Exposure-Response Relationships for the Antibody-Drug Conjugate
      Brentuximab Vedotin in CTCL Patients in the Phase III ALCANZA Study.
AB  - The antibody-drug conjugate (ADC) brentuximab vedotin consists of the CD30
      directed antibody attached to the microtubule-disrupting agent monomethyl
      auristatin E (MMAE). In pharmacokinetic models, including data from six studies
      (380 patients with classical Hodgkin's, systemic anaplastic large-cell, and
      cutaneous T-cell (CTCL) lymphomas), lower clearance of ADC and modestly higher
      ADC exposure in CTCL patients did not translate into higher MMAE exposure. In
      CTCL patients from the phase III ALCANZA study (n = 66), improved progression
      free survival with brentuximab vedotin vs. controls was not related to ADC
      exposure. ADC exposure was a predictor of grade >=3 treatment-emergent adverse
      events (TEAEs). Results support the consistent benefit observed with brentuximab
      vedotin 1.8 mg/kg every 3 weeks across the range of exposures in ALCANZA and
      support dose reductions in patients experiencing TEAEs at the starting dose.

PMID- 29377078
TI  - Impact of climate change on dermatological conditions related to flooding: update
      from the International Society of Dermatology Climate Change Committee.
AB  - Climate change contributes to the increase in severity and frequency of flooding,
      which is the most frequent and deadly disaster worldwide. Flood-related damage
      can be very severe and include health effects. Among those health impacts,
      dermatological diseases are one of the most frequently encountered. Both
      infectious and noninfectious dermatological conditions are increasing after
      flooding. We searched PubMed using the search term climate change OR global
      warming OR rainfall OR flooding OR skin. Articles published in the English
      language literature were included. We also searched the International Society of
      Dermatology website library on climate change for additional articles. There is
      an increased risk of trauma during the course of a natural disaster. The majority
      of post-tsunami wound infections were polymicrobial, but gram-negative bacteria
      were the leading causes. Infectious diseases with dermatological manifestations,
      such as impetigo, leptospirosis, measles, dengue fever, tinea corporis, malaria,
      and leishmaniasis, are important causes of morbidity among flood-afflicted
      individuals. Insect bites and stings, and parasite infestations such as scabies
      and cutaneous larva migrans are also frequently observed. Inflammatory conditions
      including irritant contact dermatitis are among the leading dermatological
      conditions. Dermatological conditions such as alopecia areata, vitiligo,
      psoriasis, and urticaria can be induced or exacerbated by psychological
      conditions post disaster. Prevention is essential in the management of skin
      diseases because of flooding. Avoiding exposure to contaminated environments,
      wearing protective devices, rapid provision of clean water and sanitation
      facilities, prompt vector controls, and education about disease risk and
      prevention are important.

PMID- 29377080
TI  - Topical benzydamine hydrochloride for prevention of postoperative sore throat in
      adults undergoing tracheal intubation for elective surgery: a systematic review
      and meta-analysis.
AB  - Postoperative sore throat has a negative impact on patient satisfaction and
      recovery. Benzydamine hydrochloride is a non-steroidal anti-inflammatory drug
      available for topical use. We performed a systematic review and meta-analysis to
      assess the efficacy and safety of topical application of benzydamine to prevent
      postoperative sore throat in adults undergoing elective surgery under general
      anaesthesia. We searched PubMed, EMBASE, Web of Science and the Cochrane Central
      Register of Controlled Trials to identify relevant randomised controlled trials
      and pooled the data using a random effects model. The primary outcomes were the
      incidence and severity of sore throat 24 h after surgery/extubation, and adverse
      events. The quality of evidence was assessed using the grading of
      recommendations, assessment, development and evaluation (GRADE) criteria.
      Thirteen randomised controlled trials involving 1842 patients were included.
      Compared with control patients who did not receive analgesia, benzydamine was
      associated with a decreased incidence of postoperative sore throat, with a risk
      ratio (95%CI) of 0.31 (0.20-0.47), but not with significantly reduced severity,
      the standardised mean difference (95%CI) being -0.27 (-0.63 to 0.08). There were
      no significant adverse events related to benzydamine. Benzydamine was also
      associated with a reduced incidence of postoperative sore throat when compared
      with lidocaine, with a risk ratio (95%CI) of 0.18 (0.07-0.43). We judged the
      evidence for the outcome 'incidence of postoperative sore throat' as high
      quality.

PMID- 29377079
TI  - Incidence of diseases primarily affecting the skin by age group: population-based
      epidemiologic study in Olmsted County, Minnesota, and comparison with age
      specific incidence rates worldwide.
AB  - Understanding the effects of age on the epidemiology of diseases primarily
      affecting the skin is important to the practice of dermatology, both for proper
      allocation of resources and for optimal patient-centered care. To fully
      appreciate the effect that age may have on the population-based calculations of
      incidence of diseases primarily affecting the skin in Olmsted County, Minnesota,
      and worldwide, we performed a review of all relevant Rochester Epidemiology
      Project-published data and compared them to similar reports in the worldwide
      English literature. Using the Rochester Epidemiology Project, population-based
      epidemiologic studies have been performed to estimate the incidence of specific
      skin diseases over the past 50 years. In older persons (>65 years), nonmelanoma
      skin cancer, lentigo maligna, herpes zoster, delusional infestation, venous
      stasis syndrome, venous ulcer, and burning mouth syndrome were more commonly
      diagnosed. In those younger than 65 years, atypical nevi, psoriatic arthritis,
      pityriasis rosea, herpes progenitalis, genital warts, alopecia areata,
      hidradenitis suppurativa, infantile hemangioma, Behcet's disease, and sarcoidosis
      (isolated cutaneous, with sarcoidosis-specific cutaneous lesions and with
      erythema nodosum) had a higher incidence. Many of the incidence rates by age
      group of diseases primarily affecting the skin derived from the Rochester
      Epidemiology Project were similar to those reported elsewhere.

PMID- 29377081
TI  - Three-dimensional genome architecture in health and disease.
AB  - More than a decade of massive DNA sequencing efforts have generated a large body
      of genomic, transcriptomic and epigenomic information that has provided a more
      and more detailed view of the functional elements and transactions within the
      human genome. Considerable efforts have also focused on linking these elements
      with one another by mapping their interactions and by establishing 3-dimensional
      (3D) genomic landscapes in various cell and tissue types. In parallel, multiple
      studies have associated genomic deletions, duplications and other rearrangements
      with human pathologies. In this review, we explore recent progresses that have
      allowed connecting disease-causing alterations with perturbations of the 3D
      genome organization.

PMID- 29377082
TI  - Genetic diversity and toxin gene distribution among serovars of Actinobacillus
      pleuropneumoniae from Australian pigs.
AB  - OBJECTIVE: To explore the diversity among isolates of the Actinobacillus
      pleuropneumoniae serovars most common in Australia (serovars 1, 5, 7 and 15) and
      to examine the Apx toxin profiles in selected representative isolates. DESIGN: A
      total of 250 isolates selected from different farms were examined for their
      genotypic profiles and a subset of 122 isolates for their toxin profiles.
      METHODS: The isolates of serovars 1, 5, 7 and 15 selected for this study came
      from different farms and different Australian states and were submitted for
      serotyping to the reference laboratory. The overall diversity of the strains was
      explored with the enterobacterial repetitive intergenic consensus (ERIC) PCR and
      the presence of the toxin genes was investigated with a toxin PCR assay. RESULTS:
      Some degree of variation was observed in the ERIC-PCR pattern within all four
      serovars, ranging from 38% to 61% genetic diversity. When looking at the toxin
      gene profile and, therefore, the predicted ability to produce the expected toxin
      pattern, one isolate each of serovars 1 (n = 20) and 7 (n = 47) and 17 isolates
      of serovar 15 (n = 40) showed variation to the expected gene profile. CONCLUSION:
      The variations in toxin gene patterns, as detected by PCR, found in this study
      could be related to significant changes in the gene sequence or total absence of
      the gene. Variation in toxin gene sequences has been observed in other countries.
      This variation in the toxin profile could also explain possible variation in
      pathogenicity observed in the field.

PMID- 29377084
TI  - Peter Bryan Spradbrow 1934-2017.

PMID- 29377085
TI  - Modified rib pivot lateral thoracotomy: a case series.
AB  - OBJECTIVE: To describe a modified rib pivot thoracotomy and its clinical
      application in client-owned dogs and cats. STUDY DESIGN: Case series of 24 dogs
      and 1 cat requiring a thoracotomy. METHODS: A lateral thoracic incision over the
      required thoracic segment was made. The latissimus dorsi muscle was reflected
      dorsally. The predetermined rib was identified and the periosteum overlying the
      rib was elevated circumferentially, avoiding the intercostal neurovascular
      structures. Holes were pre-placed above and below the proposed osteotomy site.
      The rib was osteotomised and pivoted cranially. The pleura was incised and the
      required intrathoracic procedure was then performed. The thoracic cavity was
      closed by pre-placement of a suture through the pre-placed holes within the
      osteotomised rib. The pleura and intercostal musculature were closed, avoiding
      the intercostal neurovascular structures. The rib was re-apposed and the lateral
      approach was closed. The cases included were reviewed for both the rib pivoted as
      per the procedure required and postoperative complications. RESULTS: The study
      group comprised 8 Staffordshire Bull Terriers, 2 Poodles, 2 German Shepherd Dogs,
      1 each of Basset Hound, Rhodesian Ridgeback, Golden Retriever, Australian
      Shepherd, Vizsla, Bull Mastiff, Schnauzer, Jack Russell Terrier, Bulldog,
      Deerhound, Labrador Retriever and Australian Terrier, and 1 cat. A modified rib
      pivot thoracotomy was performed for lung lobectomy (n = 11), oesophagectomy (7),
      subtotal pericardectomy (5), patent ductus arteriosus ligation (1) and thoracic
      duct ligation (1). Follow-up ranged from 2 to 40 weeks postoperatively.
      Postoperative complications included seroma formation in two dogs. CONCLUSION: A
      modified rib pivot thoracotomy should be considered as an alternative lateral
      thoracic approach with good exposure, minimal complications and low morbidity.

PMID- 29377087
TI  - Clinical features and management of schwannoma affecting the upper and lower
      lips.
AB  - Head and neck schwannomas comprise 25-40% of all schwannomas, with presentation
      on the lips as the rarest and most surgically complicated site for perioral
      tumors. A systematic literature review was conducted to include 21 cases of
      patients with schwannoma of the upper or lower lips. The majority of patients
      presented with a single, painless, well-encapsulated nodule on the upper or lower
      lips. The nodules were consistently slow-growing, with an average 29.3 months
      from symptom onset to clinical presentation. Most cases were complicated by
      profound cosmetic disfigurement as well as dysphagia, dysarthria, snoring, and/or
      sleep apnea. Overall, histological analysis was consistent with classic
      schwannoma, and all cases were treated via complete surgical excision, and for
      malignant tumors, additional therapy was utilized. All but four cases achieved
      full remission by final follow-up. Recurrence rate for benign lip schwannomas was
      5.3%, which is remarkably different from the standard recurrence rate of 8-24%
      for benign peripheral schwannomas. Additionally, the proportion of malignant
      tumors was greater for lip schwannomas than other schwannomas. Lip schwannomas
      demonstrate different characteristics than schwannomas from other locations on
      the body, and these remarkable differences highlight significant implications for
      clinical practice. Complete excision is the primary mode of treatment with
      overall excellent postoperative prognosis and rare instances of recurrence. Given
      the rarity of this tumor, this review of available cases serves to
      comprehensively describe clinical presentation and surgical treatment approaches
      to upper and lower lip schwannomas.

PMID- 29377088
TI  - Community divergence and convergence along experimental gradients of stress and
      disturbance.
AB  - We created 24 mesocosms containing mixtures of herbaceous species arranged along
      experimentally maintained gradients of stress (external abiotic constraints
      limiting biomass production) and disturbance (events causing partial or total
      live biomass destruction) in order to determine the degree to which community
      assembly is deterministic or historically contingent during succession. In this 7
      yr experiment, we found taxonomic divergence and functional convergence during
      the last 3 yr. Although communities became more functionally dissimilar as the
      difference in the level of stress increased, they were equally taxonomically
      different irrespective of the amount of difference between them in terms of
      stress and disturbance. In addition, comparing communities experiencing the same
      conditions, taxonomic community structure was more dissimilar as the levels of
      stress and disturbance decreased. Therefore, community assembly was largely
      deterministic from a functional perspective but more historically contingent from
      a taxonomic perspective, and the relative importance of taxonomic historical
      contingency decreased as the levels of stress and disturbance frequency
      increased.

PMID- 29377089
TI  - Topical Paromomycin for treating solitary mucosal leishmaniasis.

PMID- 29377090
TI  - Harlequin ichthyosis due to novel splice site mutation in the ABCA12 gene:
      postnatal to prenatal diagnosis.
AB  - BACKGROUND: Harlequin ichthyosis (HI) is a severe genetic disorder caused by the
      mutation in the ABCA12 gene. Infants born with this condition have markedly
      thickened, hard stratum corneum skin all over the body. METHODS: A female child
      born with a thick white plate of skin with deep cracks all over the body was
      investigated for genes associated with congenital Ichthyosis by Next Generation
      sequencing. The variant relevant to the clinical indications was identified using
      Picard and GATK version 3.6. Variant's pathogenicity was predicted by "in silico"
      tools like Mutation Taster 2, Mutation Assessor and LRT. Bidirectional Sanger
      sequencing further validated the same variant detected in the proband and
      confirmed in the parental blood and CVS. RESULTS: A homozygous 5' splice site
      variation that affects the position at 4 nucleotides downstream to the donor
      proximal splice site of intron 40 (c.5939+4A>G; ENST00000272895) of the ABCA12
      gene was detected in the proband, and the parents were heterozygous for the same
      variant. This led to the confirmation of diagnosis of Harlequin ichthyosis in the
      proband. "In silico" prediction of the variant was found to be damaging by
      MutationTaster2. The CVS sample during subsequent pregnancy was confirmed to be
      heterozygous for the same variant. CONCLUSIONS: The novel intronic mutation found
      in the proband confirmed the clinical diagnosis as a severe type of HI and has
      helped the family in providing precise genetic counseling for further prevention
      of the disease and carrier screening of other family members.

PMID- 29377091
TI  - Pathogenesis and treatment options for chemotherapy-induced alopecia: a
      systematic review.
AB  - Chemotherapy-induced alopecia (CIA) is one of the most troubling long-lasting
      side effects of cancer treatment. An estimated 65% of patients undergoing classic
      chemotherapy will experience hair loss, which is an extremely upsetting adverse
      event for many. CIA has been traditionally considered to be a diffuse,
      nonscarring alopecia; however, there are increasing reports of permanent hair
      loss post chemotherapy. Despite its large impact on patients, there are few
      proven treatments for CIA. Recent advancements in understanding the pathogenesis
      of hair loss are promising novel preventative and therapeutic strategies.
      Currently, scalp cooling during chemotherapy is the most effective preventive
      intervention with response rates ranging from 50 to 80%. To avoid patient
      morbidity, clinicians should be aware of the pathogenesis of CIA, characteristic
      patterns of hair loss associated with specific drug regimens, preventive measures
      that may be taken, and therapeutic options post chemotherapy. The following
      represents an updated systematic review of CIA, including characteristic clinical
      patterns, pathophysiology of the disease, therapeutic approaches, as well as a
      cost-effective analysis to assess the significance of this toxicity.

PMID- 29377092
TI  - Nest webs beyond woodpeckers: the ecological role of other nest builders.

PMID- 29377093
TI  - Environmental filtering and phylogenetic clustering correlate with the
      distribution patterns of cryptic protist species.
AB  - The community composition of any group of organisms should theoretically be
      determined by a combination of assembly processes including resource
      partitioning, competition, environmental filtering, and phylogenetic legacy.
      Environmental DNA studies have revealed a huge diversity of protists in all
      environments, raising questions about the ecological significance of such
      diversity and the degree to which they obey to the same rules as macroscopic
      organisms. The fast-growing cultivable protist species on which hypotheses are
      usually experimentally tested represent only a minority of the protist diversity.
      Addressing these questions for the lesser known majority can only be inferred
      through observational studies. We conducted an environmental DNA survey of the
      genus Nebela, a group of closely related testate (shelled) amoeba species, in
      different habitats within Sphagnum-dominated peatlands. Identification based on
      the mitochondrial cytochrome c oxidase 1 gene, allowed species-level resolution
      as well as phylogenetic reconstruction. Community composition varied strongly
      across habitats and associated environmental gradients. Species showed little
      overlap in their realized niche, suggesting resource partitioning, and a strong
      influence of environmental filtering driving community composition. Furthermore,
      phylogenetic clustering was observed in the most nitrogen-poor samples,
      supporting phylogenetic inheritance of adaptations in the group of N. guttata.
      This study showed that the studied free-living unicellular eukaryotes follow to
      community assembly rules similar to those known to determine plant and animal
      communities; the same may be true for much of the huge functional and taxonomic
      diversity of protists.

PMID- 29377094
TI  - GAPO syndrome: a rare genodermatosis presenting with unique features.

PMID- 29377095
TI  - Development and assessment of the Quality of Life in Childhood Epilepsy
      Questionnaire (QOLCE-16).
AB  - OBJECTIVE: The aim of this study was to develop and validate a brief version of
      the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). A secondary aim
      was to compare the results described in previously published studies using the
      QOLCE-55 with those obtained using the new brief version. METHODS: Data come from
      373 children involved in the Health-related Quality of Life in Children with
      Epilepsy Study, a multicenter prospective cohort study. Item response theory
      (IRT) methods were used to assess dimensionality and item properties and to guide
      the selection of items. Replication of results using the brief measure was
      conducted with multiple regression, multinomial regression, and latent mixture
      modeling techniques. RESULTS: IRT methods identified a bi-factor graded response
      model that best fits the data. Thirty-nine items were removed, resulting in a 16
      item QOLCE (QOLCE-16) with an equal number of items in all 4 domains of
      functioning (Cognitive, Emotional, Social, and Physical). Model fit was
      excellent: Comparative Fit Index = 0.99; Tucker-Lewis Index = 0.99; root mean
      square error of approximation = 0.052 (90% confidence interval [CI] 0.041-0.064);
      weighted root mean square = 0.76. Results that were reported previously using the
      QOLCE-55 and QOLCE-76 were comparable to those generated using the QOLCE-16.
      SIGNIFICANCE: The QOLCE-16 is a multidimensional measure of health-related
      quality of life (HRQoL) with good psychometric properties and a short-estimated
      completion time. It is notable that the items were calibrated using
      multidimensional IRT methods to create a measure that conforms to conventional
      definitions of HRQoL. The QOLCE-16 is an appropriate measure for both clinicians
      and researchers wanting to record HRQoL information in children with epilepsy.

PMID- 29377096
TI  - Delayed myelination and neurodevelopment in male seizure-prone versus seizure
      resistant rats.
AB  - OBJECTIVE: Aberrant myelination and developmental delay have been reported in
      epilepsy. However, it is unclear whether these are linked to intrinsic mechanisms
      that support a predisposition toward seizures and the development of epilepsy.
      Thus, we compared rates of myelination and neurodevelopment in male rats
      selectively bred for enhanced susceptibility to kindling epileptogenesis (FAST)
      with male rats bred for resistance (SLOW). METHODS: Myelin-specific gene
      expression was compared in the brainstem, cerebellum, and cerebral hemisphere of
      FAST and SLOW rats on postnatal days (PNDs) 5, 11, 17, 23, and 90 to determine
      strain-specific myelination rates. Myelin protein levels were also compared at
      PNDs 5 and 23 in the brainstem. Relative rates of neurodevelopment were evaluated
      between PNDs 5 and 21 using physical growth landmarks and neuromotor tests
      including righting reflex, cliff avoidance, negative geotaxis, and locomotor
      activity. RESULTS: Myelin-specific mRNA expression was significantly down
      regulated in FAST rats on PNDs 5 and 11 in all 3 brain structures, indicating
      relatively delayed myelination. Likewise, corresponding protein levels were
      significantly lower in FAST brainstem on PND 5. Developmental delay was evident
      in the FAST strain such that only 9% of FAST pups, compared to 81% of SLOW, had
      open eyes by PND 13, locomotor activity was significantly reduced between PNDs 12
      and 16, and neuromotor task acquisition was delayed between PNDs 5 and 10.
      SIGNIFICANCE: Relative delays in myelination and neurodevelopment co-occurred in
      the seizure-prone FAST strain in the absence of seizures. These findings suggest
      these symptoms are not seizure-induced and may be mechanistically linked to an
      underlying pathophysiology supporting a predisposition toward developing
      epilepsy.

PMID- 29377098
TI  - PCDH19-related epilepsy is associated with a broad neurodevelopmental spectrum.
AB  - OBJECTIVE: To characterize the features associated with PCDH19-related epilepsy,
      also known as "female-limited epilepsy." METHODS: We analyzed data from
      participants enrolled in the PCDH19 Registry, focusing on the seizure-related,
      developmental, neurobehavioral, and sleep-related features. We evaluated variants
      for pathogenicity based on previous reports, population databases, and in silico
      predictions, and included individuals with pathogenic or potentially pathogenic
      variants. We performed a retrospective analysis of medical records and
      administered a targeted questionnaire to characterize current or past features in
      probands and genotype-positive family members. RESULTS: We included 38
      individuals with pathogenic or potentially pathogenic variants in PCDH19: 21 de
      novo, 5 maternally inherited, 7 paternally inherited, and 5 unknown. All 38 had
      epilepsy; seizure burden varied, but typical features of clustering of seizures
      and association with fever were present. Thirty individuals had intellectual
      disability (ID), with a wide range of severity reported; notably, 8/38 (22%) had
      average intellect. Behavioral and sleep dysregulation were prominent, in 29/38
      (76%) and 20/38 (53%), respectively. Autistic features were present in 22/38
      (58%), of whom 12 had a formal diagnosis of autism spectrum disorder. We had
      additional data from 5 genotype-positive mothers, all with average intellect and
      3 with epilepsy, and from 1 genotype-positive father. SIGNIFICANCE: Our series
      represents a robust cohort with carefully curated PCDH19 variants. We observed
      seizures as a core feature with a range of seizure types and severity. Whereas
      the majority of individuals had ID, we highlight the possibility of average
      intellect in the setting of PCDH19-related epilepsy. We also note the high
      prevalence and severity of neurobehavioral phenotypes associated with likely
      pathogenic variants in PCDH19. Sleep dysregulation was also a major area of
      concern. Our data emphasize the importance of appropriate referrals for formal
      neuropsychological evaluations as well as the need for formal prospective studies
      to characterize the PCDH19-related neurodevelopmental syndrome in children and
      their genotype-positive parents.

PMID- 29377099
TI  - A Western dietary pattern is associated with elevated level of high sensitive C
      reactive protein among adolescent girls.
AB  - BACKGROUND: Serum high sensitive C-reactive protein (hs-CRP), is an indicator of
      low-grade inflammation, and is associated with several non-communicable diseases.
      The effects of diet on inflammation have not been extensively investigated,
      particularly among adolescents. We aimed to examine the association between major
      dietary patterns and elevated serum level of hs-CRP among Iranian adolescent
      girls. MATERIALS AND METHODS: In this cross-sectional study, a total of 670
      adolescent girls were recruited from several schools in different areas of
      Mashhad and Sabzevar cities, Iran. The dietary intakes of study participants were
      collected using a 147-item food frequency questionnaire. To identify major
      dietary patterns based on the 40 food groups, we used principal component
      analysis. Serum concentration of hs-CRP was measured using commercial kits and
      the BT-3000 auto-analyser. To investigate the association between dietary
      patterns and elevated serum level of hs-CRP, we used logistic regression
      analysis. RESULTS: Three specific dietary patterns were identified: (i) healthy,
      (ii) traditional and (iii) western dietary patterns. A significant association
      was found between more adherence to Western dietary pattern and elevated serum
      level of hs-CRP (OR: 1.58; 95% CI: 1.02-2.42, P-trend = .03); these association
      remained significant after adjustment for potential confounders. However, there
      was no significant relationship between healthy and traditional dietary patterns
      and elevated serum level of hs-CRP. CONCLUSION: Our results indicate that there
      is a significant positive association between more adherence to Western dietary
      pattern and higher serum levels of hs-CRP among Iranian adolescent girls. Further
      studies, particularly longitudinal intervention studies may be required to
      clarify these relationships.

PMID- 29377100
TI  - Substrate-induced structural alterations of Mycobacterial mycothione reductase
      and critical residues involved.
AB  - Redox homeostasis is a prerequisite for survival of the pathogen Mycobacterium
      tuberculosis (Mtb) which employs the low molecular weight thiol mycothiol (MSH).
      The Mycobacterial NADPH-dependent mycothione reductase (MtMtr), composed of an
      NADPH-, FAD-, and a dimerization-domain connected by linkers, regulates the
      balance of oxidized-reduced MSH. Here, we demonstrate by small-angle X-ray
      scattering, that NADPH-binding alters the oligomeric state equilibrium of the
      protein with no significant overall structural change after MSH-binding. Mutation
      of critical residues in the linker regions of MtMtr eliminate partially or
      totally the NADPH-induced oligomerization effect with simultaneous effect on
      enzyme activity. The data provide insight into the MtMtr linker regions involved
      in the novel oligomerization equilibrium of the Mycobacterial enzyme.

PMID- 29377101
TI  - Can there be a moral obligation to participate in biomedical research?
AB  - In clinical medicine, the moral obligation to care for the individual patient is
      absolute. Patient care means at least and by negative terms to minimize any risk
      of treatment. In this context, the question arises about the compatibility of
      clinical ethics and human biomedical research ethics. Or conversely, is there a
      common ground between the two? At the opposite end of the field between clinical
      ethics and biomedical research ethics is the proposal of an obligation to
      participate in biomedical research, which is argued for on the basis of
      biomedical knowledge being a public good available to the community as a whole.
      While patient accrual during a clinical investigation would certainly be
      facilitated by obligatory research participation, and the data obtained would be
      at first sight-more representative for the population studied, the still feasible
      refusal to participate would be stigmatizing and as such detrimental for the
      patient-physician relation. This essay seeks to provide a reply to the titled
      question by focusing on aspects such as individual vs common medical claims,
      shared grounds between the two and an important document of medical research
      ethics, that is the Nuremberg code.

PMID- 29377103
TI  - Effect of Nanoparticle Surface Coating on Cell Toxicity and Mitochondria Uptake.
AB  - We report on the effect of surface charge and the ligand coating composition of
      CdSe/ZnS core/shell quantum dot (QD) nanoparticles on human keratinocyte toxicity
      using fluorescent microscopy, flow cytometry, transmission electron microscopy.
      Two commonly reported positive charged (cysteamine, polyethylenimine) and two
      negative charged (glutathione, dihydrolipoic acid) ligands were studied. The QDs
      were fully characterized by UV-vis absorption spectroscopy, fluorescence emission
      spectroscopy, dynamic light scattering and zeta potential. Differences in surface
      coatings and charges were evaluated against cellular uptake, ROS generation,
      cytotoxicity, and mitochondrial targeting. Results show that the negative charged
      QDs coated with GSH exhibit excellent water solubility, high quantum yield and
      low cytotoxicity. Ligand composition is more important in ROS generation than
      surface charge whereas surface charge is an important driver of cytotoxicity.
      Most importantly we observe the selective accumulation of glutathione coated QDs
      in vesicles in the mitochondria matrix. This observation suggests a new strategy
      for developing mitochondria-targeted nanomaterials for drug/gene delivery.

PMID- 29377102
TI  - Cholera toxin enhances interleukin-17A production in both CD4+ and CD8+ cells via
      a cAMP/protein kinase A-mediated interleukin-17A promoter activation.
AB  - Cholera toxin (CT) is a bacterial component that increases intracellular cAMP
      levels in host cells and suppresses T-cell activation. Recently, CT was reported
      to induce T helper type 17-skewing dendritic cells and activate interleukin-17A
      (IL-17A) production in CD4+ T cells through a cAMP-dependent pathway. However,
      the underlying mechanism by which cAMP regulates IL-17A production in T cells is
      not completely defined. In this study, we took advantage of a small molecule
      protein kinase A (PKA) inhibitor (H89) and different cAMP analogues: a PKA
      specific activator (N6-benzoyl-adenosine-cAMP), an exchange protein activated by
      cAMP-specific activator (Rp-8-chlorophenylthio-2'-O-methyl cAMP), and a PKA
      inhibitor (Rp-8-bromo-cAMP), to elucidate the signalling cascade of cAMP in IL
      17A regulation in T cells. We found that CT induced IL-17A production and IL-17A
      promoter activity in activated CD4+ T cells through a cAMP/PKA pathway. Moreover,
      this regulation was via cAMP-response element binding protein (CREB) -mediated
      transcriptional activation by using the transfection of an IL-17A promoter
      luciferase reporter construct and CREB small interfering RNA in Jurkat cells.
      Also, we showed that CREB bound to the CRE motif located at -183 of the IL-17A
      promoter in vitro. Most interestingly, not only in CD4+ T cells, CT also enhanced
      cAMP/PKA-dependent IL-17A production and CREB phosphorylation in CD8+ T cells. In
      conclusion, our data suggest that CT induces an IL-17A-dominated immune
      microenvironment through the cAMP/PKA/CREB signalling pathway. Our study also
      highlights the potentials of CT and cAMP in modulating T helper type 17 responses
      in vivo.

PMID- 29377104
TI  - Chemical Composition of Date Palm (Phoenix dactylifera L.) Seed Oil from Six
      Saudi Arabian Cultivars.
AB  - : This investigation aimed to evaluate the chemical composition and
      physicochemical properties of seed oils from 6 date palm (Phoenix. dactylifera
      L.) cultivars (Barhi, Khalas, Manifi, Rezeiz, Sulaj, and Sukkari) growing in
      Saudi Arabia and to compare them with conventional palm olein. The mean oil
      content of the seeds was about 7%. Oleic acid (48.67%) was the main fatty acid,
      followed by lauric acid (17.26%), stearic acid (10.74%), palmitic acid (9.88%),
      and linolenic acid (8.13%). The mean value for free fatty acids content was 0.5%.
      The P. dactylifera seed oil also exhibited a mean tocol content of 70.75 mg/100
      g. alpha-Tocotrienol was the most abundant isomer (30.19%), followed by gamma
      tocopherol (23.61%), gamma-tocotrienol (19.07%), and alpha-tocopherol (17.52%).
      The oils showed high thermal and oxidative stabilities. The findings indicate
      that date seed oil has the potential to be used in the food industry as an
      abundant alternative to palm olein. PRACTICAL APPLICATION: This study showed that
      date seed had great nutritional value due to which it can be used for food
      applications especially as frying or cooking oil. In addition, date oil has also
      potential to be used in cosmetic and pharmaceutical practices as well. The
      extraction of oil from Phoenix dactylifera seed on large scale can create
      positive socioeconomic benefits especially for rural communities and could also
      assist to resolve the environmental issues generated by excess date production in
      large scale date-producing countries such as Saudi Arabia.

PMID- 29377105
TI  - Paediatric oral pathology in Thailand: a 15-year retrospective review from a
      medical teaching hospital.
AB  - OBJECTIVES: To determine whether the spectrum of oral pathology in children seen
      at a medical institution differs from studies derived from dental facilities.
      METHODS: Oral biopsy records from paediatric patients (<16 years of age) were
      retrieved from the pathology archives at Chulalongkorn University Hospital over a
      period of 15 years. Lesions were categorised as inflammatory/reactive,
      tumour/tumour-like or cystic. RESULTS: Two-hundred and thirty biopsies were
      identified. Most lesions were inflammatory/reactive (62%), followed by
      tumour/tumour-like (35%) and cystic (3%). The largest proportion of lesions was
      found in the 12-16 years' age group. Mucocele was the most common lesion (38%),
      followed by hemangioma (8.3%), irritation fibroma (6%) and nevus (6%). The
      predominance of mucocele is similar to that in reports from other countries. The
      proportion of malignant tumours (5%) was higher than in other studies (<1-2%). In
      contrast, odontogenic cysts and odontogenic tumours were rare (3% and <1%,
      respectively), compared with published studies (7-35% and 2-21%, respectively).
      CONCLUSIONS: This study from a medical institution shows a somewhat different
      spectrum of paediatric oral pathology compared with that reported from dental
      institutions. While some of the lesions may not be treated by dentists, they
      still need to be aware of these lesions because affected patients can still
      present initially to a dentist.

PMID- 29377106
TI  - Modulation of GSK3beta autoinhibition by Thr-7 and Thr-8.
AB  - Glycogen synthase kinase 3beta (GSK-3beta) is a pivotal signaling node that
      regulates a myriad of cellular functions and is deregulated in many pathological
      conditions, making it an attractive therapeutic target. Inhibitory Ser-9
      phosphorylation of GSK3beta by AKT is an important mechanism for negative
      regulation of GSK3beta activity upon insulin stimulation. Here, we report that
      Thr-7 and Thr-8 residues located in the AKT/PKB substrate consensus sequence on
      GSK3beta are essential for insulin-stimulated Ser-9 phosphorylation in vivo and
      for GSK3beta inactivation. Intestinal cell kinase (ICK) phosphorylates GSK3beta
      Thr-7 in vitro and in vivo. Thr-8 phosphorylation partially inhibits GSK3beta,
      but Thr-7 phosphorylation promotes GSK3beta activity and blocks phospho-Ser-9
      dependent GSK3beta autoinhibition. Our findings uncover novel mechanistic and
      signaling inputs involved in the autoinhibition of GSK3beta.

PMID- 29377107
TI  - Daily very low UV dose exposure enhances adaptive immunity, compared with a
      single high-dose exposure. Consequences for the control of a skin infection.
AB  - Ultraviolet radiation (UVr) promotes several well-known molecular changes, which
      may ultimately impact on health. Some of these effects are detrimental, like
      inflammation, carcinogenesis and immunosuppression. On the other hand, UVr also
      promotes vitamin D synthesis and other beneficial effects. We recently
      demonstrated that exposure to very low doses of UVr on four consecutive days
      [repetitive low UVd (rlUVd)] does not promote an inflammatory state, nor the
      recruitment of neutrophils or lymphocytes, as the exposure to a single high UV
      dose (shUVd) does. Moreover, rlUVd reinforce the epithelium by increasing
      antimicrobial peptides transcription and epidermal thickness. The aim of this
      study was to evaluate the adaptive immune response after shUVd and rlUVd,
      determining T-cell and B-cell responses. Finally, we challenged animals exposed
      to both irradiation procedures with Staphylococcus aureus to study the overall
      effects of both innate and adaptive immunity during a cutaneous infection. We
      observed, as expected, a marked suppression of T-cell and B-cell responses after
      exposure to an shUVd but a novel and significant increase in both specific
      responses after exposure to rlUVd. However, the control of the cutaneous S.
      aureus infection was defective in this last group, suggesting that responses
      against pathogens cannot be ruled out from isolated stimuli.

PMID- 29377108
TI  - Regulation of RhoA GTPase and various transcription factors in the RhoA pathway.
AB  - RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins,
      cellular morphology, and migration along with various proliferation and
      transcriptional activity in cells. RhoA activity is regulated by guanine
      nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the
      guanine nucleotide dissociation factor (GDI). The RhoA-RhoGDI complex exists in
      the cytosol and the active GTP-bound form of RhoA is located to the membrane. GDI
      displacement factors (GDFs) including IkappaB kinase gamma (IKKgamma) dissociate
      the RhoA-GDI complex, allowing activation of RhoA through GEFs. In addition,
      modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156
      phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA
      RhoGDI complex. The expression of RhoA is regulated through transcriptional
      factors such as c-Myc, HIF-1alpha/2alpha, Stat 6, and NF-kappaB along with
      several reported microRNAs. As the role of RhoA in regulating actin-filament
      formation and myosin-actin interaction has been well described, in this review we
      focus on the transcriptional activity of RhoA and also the regulation of RhoA
      message itself. Of interest, in the cytosol, activated RhoA induces
      transcriptional changes through filamentous actin (F-actin)-dependent ("actin
      switch") or-independent means. RhoA regulates the activity of several
      transcription regulators such as serum response factor (SRF)/MAL, AP-1, NF
      kappaB, YAP/TAZ, beta-catenin, and hypoxia inducible factor (HIF)-1alpha.
      Interestingly, RhoA also itself is localized to the nucleus by an as-yet
      undiscovered mechanism.

PMID- 29377109
TI  - Trauma induced heterotopic ossification patient serum alters mitogen activated
      protein kinase signaling in adipose stem cells.
AB  - Post-traumatic heterotopic ossification (HO) is the formation of ectopic bone in
      non-osseous structures following injury. The precise mechanism for bone
      development following trauma is unknown; however, early onset of HO may involve
      the production of pro-osteogenic serum factors. Here we evaluated serum from a
      cohort of civilian and military patients post trauma to determine early induction
      gene signatures in orthopaedic trauma induced HO. To test this, human adipose
      derived stromal/stem cells (hASCs) were stimulated with human serum from patients
      who developed HO following trauma and evaluated for a gene panel with qPCR.
      Pathway gene analysis ontology revealed that hASCs stimulated with serum from
      patients who developed HO had altered gene expression in the activator protein 1
      (AP1) and AP1 transcriptional targets pathways. Notably, there was a significant
      repression in FOS gene expression in hASCs treated with serum from individuals
      with HO. Furthermore, the mitogen-activated protein kinase (MAPK) signaling
      pathway was activated in hASCs following serum exposure from individuals with HO.
      Serum from both military and civilian patients with trauma induced HO had
      elevated downstream genes associated with the MAPK pathways. Stimulation of hASCs
      with known regulators of osteogenesis (BMP2, IL6, Forskolin, and WNT3A) failed to
      recapitulate the gene signature observed in hASCs following serum stimulation,
      suggesting non-canonical mechanisms for gene regulation in trauma induced HO.
      These findings provide new insight for the development of HO and support ongoing
      work linking the systemic response to injury with wound specific outcomes.

PMID- 29377110
TI  - MicroRNA implications in the etiopathogenesis of ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease
      that affects both axial and peripheral skeletons as well as soft tissues. Recent
      investigations offer that disease pathogenesis is ascribed to a complex interplay
      of genetic, environmental, and immunological factors. Until now, there is no
      appropriate method for early diagnosis of AS and the successful available therapy
      for AS patients stay largely undefined. MicroRNAs (miRNAs), endogenous small
      noncoding RNAs controlling the functions of target mRNAs and cellular processes,
      are present in human plasma in a stable form and have appeared as possible
      biomarkers for activity, pathogenesis, and prognosis of the disease. In the
      present review, we have tried to summarize the recent findings related to miRNAs
      in AS development and discuss the possible utilization of these molecules as
      prognostic biomarkers or important therapeutic strategies for AS. Further
      examinations are needed to determine the unique miRNAs signatures in AS and
      characterize the mechanisms mediated by miRNAs in the pathology of this disease.

PMID- 29377111
TI  - Representation of the stomatopod's retinal midband in the optic lobes: Putative
      neural substrates for integrating chromatic, achromatic and polarization
      information.
AB  - Stomatopods have an elaborate visual system served by a retina that is unique to
      this class of pancrustaceans. Its upper and lower eye hemispheres encode
      luminance and linear polarization while an equatorial band of photoreceptors
      termed the midband detects color, circularly polarized light and linear
      polarization in the ultraviolet. In common with many malacostracan crustaceans,
      stomatopods have stalked eyes, but they can move these independently within three
      degrees of rotational freedom. Both eyes separately use saccadic and scanning
      movements but they can also move in a coordinated fashion to track selected
      targets or maintain a forward eyestalk posture during swimming. Visual
      information is initially processed in the first two optic neuropils, the lamina
      and the medulla, where the eye's midband is represented by enlarged regions
      within each neuropil that contain populations of neurons, the axons of which are
      segregated from the neuropil regions subtending the hemispheres. Neuronal
      channels representing the midband extend from the medulla to the lobula where
      populations of putative inhibitory glutamic acid decarboxylase-positive neurons
      and tyrosine hydroxylase-positive neurons intrinsic to the lobula have specific
      associations with the midband. Here we investigate the organization of the
      midband representation in the medulla and the lobula in the context of their
      overall architecture. We discuss the implications of observed arrangements, in
      which midband inputs to the lobula send out collaterals that extend across the
      retinotopic mosaic pertaining to the hemispheres. This organization suggests an
      integrative design that diverges from the eumalacostracan ground pattern and, for
      the stomatopod, enables color and polarization information to be integrated with
      luminance information that presumably encodes shape and motion.

PMID- 29377112
TI  - A Fast and Reliable Real-Time PCR Method for Detection of Ten Animal Species in
      Meat Products.
AB  - : Species substitution in meat products is a common problem reported worldwide.
      This type of food fraud is, typically, an intentional act for economic gain,
      using sources of low-priced meats in high-value meat products. Consequences
      include economic, health, and religious concerns. Highly sensitive and efficient
      techniques are thus required to detect meat species. This paper describes a
      method based on real-time PCR to detect 10 animal species (Bos taurus, Sus
      scrofa, Ovis aries, Capra hircus, Gallus gallus, Meleagris gallopavo, Bubalus
      bubalis, Equus caballus, Felis catus, and Canis familiaris) in meat product. The
      method combines species-specific and universal (used here as internal positive
      control) primers, and applies melt curve analysis for amplicon checking. Method
      accuracy was evaluated on 46 experimental meat mixtures and all species were
      correctly identified in all cases, at 1% test sensitivity. Analysis of 14
      commercial meat products revealed that 6 of 14 samples had nondeclared bovine
      and/or chicken material. We performed an interlaboratory comparison using the
      reference meat mixtures and commercial samples, achieving 100% of
      reproducibility. The developed test proved to be effective and reliable for
      routine analysis of meat products. PRACTICAL APPLICATION: This paper describes a
      fast and reliable method for species detection in meat products based on real
      time PCR. It can be applied for analysis of in natura or processed meat. The
      method proposed here can play an important role in controlling the origin of meat
      products, ensuring their quality and safety for the entire food industry
      producers to consumers.

PMID- 29377113
TI  - LGA-newborn from patients with pregestational obesity present reduced adiponectin
      mediated vascular relaxation and endothelial dysfunction in fetoplacental
      arteries.
AB  - Maternal obesity is associated with large-for-gestational-age (LGA) neonates and
      programming of obesity-related cardiovascular disease in the offspring, however,
      the mechanisms that lead to the later are unclear. Presently, interpretations of
      NO-dependent changes in vascular function in LGA newborn from obese mothers are
      conflicting. Adiponectin improves endothelial function by increasing eNOS
      activity and NO production. We propose that LGAs from obese mothers present a
      diminished vascular response to adiponectin; thus, affecting eNOS and AMPK
      activation. Chorionic arteries, umbilical cord and primary cultures of umbilical
      artery endothelial cells (HUAEC) were collected at term (>38 weeks) from
      uncomplicated singleton pregnancies of LGA and adequate-for-gestational (AGA)
      newborn. Vascular reactivity of chorionic plate arteries was assessed by wire
      myography. mRNA expression of adiponectin receptors 1 (AdipoR1) and AdipoR2 in
      HUAEC was determined by qPCR. Protein expression of AdipoR1, AdipoR2, AMPK,
      phospho-AMPKalphaThr172 , eNOS, and phospho-eNOSSer1177 after stimulation with
      AdipoRon was determined by Western Blot. Maximal adiponectin-induced chorionic
      artery relaxation in LGAs was diminished compared to control. In vitro studies
      showed no differences in expression of AdipoRs, total AMPK and, eNOS activation
      between groups; however, higher expression of total eNOS and AMPK activation in
      HUAEC of LGA relative to AGAs were observed. LGA HUAEC showed diminished NO
      production and eNOS activity compared to AGA in response to AdipoRon but no
      changes in AMPK activation. Placental endothelium of LGAs shows a diminished
      vascular response to adiponectin. Moreover, eNOS activation and adiponectin
      dependent NO production is lower in HUAEC of LGA from obese mothers, indicating
      they present dysfuncional placental-endothelial responses.

PMID- 29377114
TI  - The Philippines' new postabortion care policy.
AB  - In 2000, a Philippine policy clarifying the legality of medical treatment for
      women with postabortion complications was introduced to address unsafe abortion
      as a leading cause of maternal death, and reports of discrimination and abuse by
      healthcare providers against women who had abortions illegally. Despite its
      initial success as a pilot program, the policy's implementation and expansion
      were not prioritized. The incidence of unsafe abortion has increased over the
      years and, in 2009, the right to postabortion care was codified in national law,
      yet the mistreatment and abuse of women has continued in violation of medical
      ethics and the law. In 2016, following the demands of advocates and
      recommendations from national and international human rights bodies, the
      government introduced a new policy to strengthen the national framework for
      postabortion care, clarifying the legal and ethical duties of health service
      providers and offering women formal avenues for redress against abuse. The new
      policy offers useful guidance for countries that are contemplating new ways to
      strengthen the quality of postabortion care services in accordance with
      recognized standards of medical ethics and human rights.

PMID- 29377115
TI  - Perineural Spread of Recurrent Melanoma Presenting as Facial Formication.

PMID- 29377116
TI  - Neural Regulation of Bone Remodeling: Identifying Novel Neural Molecules and
      Pathways Between Brain and Bone.
AB  - The metabolism and homeostasis of skeletal system has historically been regarded
      to be associated with the endocrine system. However, such view has been expanded
      with the recognition of several neural pathways playing important roles in the
      regulation of bone metabolism via central relays. In particular, bone metabolism
      and homeostasis has been reported to be precisely modulated by the central neural
      signaling. Initiated by the finding of leptin, the axis of neural regulation on
      bone expands rapidly. Semaphorin-plexin system play an important role in the
      crosstalk between osteoclasts and osteoblasts, a complex system has also been
      identified and includes neuropeptide Y and cannabinoids. These findings
      facilitate our understanding of the central neuropeptides and neural factors in
      the modulation of bone metabolism and homeostasis, and these neuronal pathways
      also represent an area of research scenario that identifies the novel regulation
      between brain and bone. These regulatory mechanisms correlate with other
      homeostatic networks and demonstrate a more intricate and synergetic bone biology
      than previously envisioned. As such, this review summarizes the current knowledge
      of the neural regulation of bone metabolism and homeostasis as well as its role
      in skeletal diseases, and discusses the emerging challenges presented in this
      field. This article is protected by copyright. All rights reserved.

PMID- 29377117
TI  - VS2DRTI: Simulating Heat and Reactive Solute Transport in Variably Saturated
      Porous Media.
AB  - Variably saturated groundwater flow, heat transport, and solute transport are
      important processes in environmental phenomena, such as the natural evolution of
      water chemistry of aquifers and streams, the storage of radioactive waste in a
      geologic repository, the contamination of water resources from acid-rock
      drainage, and the geologic sequestration of carbon dioxide. Up to now, our
      ability to simulate these processes simultaneously with fully coupled reactive
      transport models has been limited to complex and often difficult-to-use models.
      To address the need for a simple and easy-to-use model, the VS2DRTI software
      package has been developed for simulating water flow, heat transport, and
      reactive solute transport through variably saturated porous media. The underlying
      numerical model, VS2DRT, was created by coupling the flow and transport
      capabilities of the VS2DT and VS2DH models with the equilibrium and kinetic
      reaction capabilities of PhreeqcRM. Flow capabilities include two-dimensional,
      constant-density, variably saturated flow; transport capabilities include both
      heat and multicomponent solute transport; and the reaction capabilities are a
      complete implementation of geochemical reactions of PHREEQC. The graphical user
      interface includes a preprocessor for building simulations and a postprocessor
      for visual display of simulation results. To demonstrate the simulation of
      multiple processes, the model is applied to a hypothetical example of injection
      of heated waste water to an aquifer with temperature-dependent cation exchange.
      VS2DRTI is freely available public domain software.

PMID- 29377118
TI  - Photo-Curable Metal-Chelating Coatings Offer a Scalable Approach to Production of
      Antioxidant Active Packaging.
AB  - : Synthetic metal chelators (for example, ethylenediaminetetraacetic acid, EDTA)
      are widely used as additives to control trace transition metal induced oxidation
      in consumer products. To enable removal of synthetic chelators in response to
      increasing consumer demand for clean label products, metal-chelating active food
      packaging technologies have been developed with demonstrated antioxidant efficacy
      in simulated food systems. However, prior work in fabrication of metal-chelating
      materials leveraged batch chemical reactions to tether metal-chelating ligands, a
      process with limited industrial translatability for large-scale fabrication. To
      improve the industrial translatability, we have designed a 2-step laminated photo
      grafting process to introduce metal chelating functionality onto common polymeric
      packaging materials. Iminodiacetic acid (IDA) functionalized materials were
      fabricated by photo-grafting poly(acrylic acid) onto polypropylene (PP) films,
      followed by a second photo-grafting process to graft-polymerize an IDA
      functionalized vinyl monomer (GMA-IDA). The photo-grafting was conducted under
      atmospheric conditions and was completed in 2 min. The resulting IDA
      functionalized metal-chelating material was able to chelate iron and copper, and
      showed antioxidant efficacy against ascorbic acid degradation, supporting its
      potential to be used synergistically with natural antioxidants for preservation
      of food and beverage products. The 2-step photo-grafting process improves the
      throughput of active packaging coatings, enabling potential roll-to-roll
      fabrication of metal-chelating active packaging materials for antioxidant food
      packaging applications. PRACTICAL APPLICATION: To address consumer and retail
      demands for "clean label" foods and beverages without a corresponding loss in
      product quality and shelf life, producers are seeking next generation
      technologies such as active packaging. In this work, we will report the synthesis
      of metal-chelating active packaging films, which enable removal of the synthetic
      additive, ethylenediamine tetraacetic acid. The new synthesis technique improves
      the throughput of metal-chelating active packaging coatings, enabling potential
      roll-to-roll fabrication of the materials for antioxidant food packaging
      applications.

PMID- 29377119
TI  - Secular changes in the symptom level of clinically diagnosed autism.
AB  - BACKGROUND: The prevalence of autism has been reported to have increased
      worldwide. A decrease over time in the number of autism symptoms required for a
      clinical autism diagnosis would partly help explain this increase. This study
      aimed to determine whether the symptom level of clinically diagnosed autism cases
      below age 13 had changed over time. METHODS: Parents of Swedish 9-year old twins
      (n = 28,118) participated in a telephone survey, in which symptoms and
      dysfunction/suffering related to neurodevelopmental disorders [including autism,
      but also attention-deficit/hyperactivity disorder (ADHD), Developmental
      Coordination Disorder (DCD), and Learning Disabilities (LD)] in their children
      were assessed over a 10-year period. Survey data was merged with the National
      Patient Register containing clinically registered autism diagnoses (n = 271).
      RESULTS: In individuals who had been clinically diagnosed with autism before the
      age of 13, the symptom score for autism decreased on average 30% over more than a
      decade in birth cohorts 1992-2002. There was an average decrease of 50% in the
      autism symptom score from 2004 to 2014 in individuals who were diagnosed with
      autism at ages 7-12, but there was no decrease in those diagnosed at ages 0-6.
      CONCLUSIONS: Over time, considerably fewer autism symptoms seemed to be required
      for a clinical diagnosis of autism, at least for those diagnosed after the
      preschool years. The findings add support for the notion that the observed
      increase in autism diagnoses is, at least partly, the by-product of changes in
      clinical practice, and flag up the need for working in agreement with best
      practice guidelines.

PMID- 29377120
TI  - Human Milk Oligosaccharides Attenuate Antigen-Antibody Complex Induced Chemokine
      Release from Human Intestinal Epithelial Cell Lines.
AB  - : There has been increased interest in the use of dietary ingredients, including
      prebiotics such as human-milk oligosaccharides (HMOs), as therapeutic strategies
      for food allergy. Understanding the mechanisms underlying the beneficial effects
      of HMOs is important to realizing their therapeutic potential. Here we
      demonstrate that the HMO, 6'-sialyllactose (6'SL) inhibited chemokine (IL-8 and
      CCL20) release from T-84 and HT-29 cells stimulated with antigen-antibody
      complex, TNFalpha or PGE2 ; an effect that was PPARgamma dependent and associated
      with decreased activity of the transcription factors AP-1 and NFkappaB. In
      contrast, 2'-fucosyllactose (2'FL) selectively inhibited CCL20 release in
      response to antigen antibody complex in a PPARgamma independent manner. This
      study reinforces the concept that structurally different oligosaccharides have
      distinct biological activities and identifies, for the first time, that the HMOs,
      6'SL, and 2'FL, modulate human epithelial cell responses related to allergic
      disease. These findings encourage further investigation of the therapeutic
      potential of specific HMOs in food allergy. PRACTICAL APPLICATION: This study
      provides evidence for direct effects of HMOs in addition to their prebiotic role
      and demonstrates, for the first time, modulation of Ag-IgE complex activation of
      human epithelial cells that may have important implications for food-allergy. The
      study also reinforces the concept that structurally different oligosaccharides
      have distinct biological activities. In determining the composition of infant
      formula, addition of oligosaccharides with specific structures may provide direct
      modulation of immune responses and potentially attenuate symptoms or development
      of food allergy.

PMID- 29377121
TI  - Prognostic significance of tumor-infiltrating lymphocytes in nondisseminated
      nasopharyngeal carcinoma: A large-scale cohort study.
AB  - The American Joint Committee on Cancer (AJCC) staging system is inadequate for an
      accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are
      under intense investigation. Here, we investigated whether the density of TILs
      could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal
      carcinoma samples from two independent cohorts to evaluate the density and
      distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we
      assessed associations between TILs and clinical outcomes in 593 randomly selected
      samples (defined as the training set) and validated findings in the remaining 593
      samples (defined as the validation set). Furthermore, we confirmed the prognostic
      value of TILs in a second independent cohort of 304 cases (defined as the
      independent set). Based on multivariable Cox regression analysis, we also
      established an effective prognostic nomogram including TILs to improve accuracy
      in predicting disease-free survival (DFS) for patients with nondisseminated NPC.
      We found that high TILs in the training set were significantly associated with
      favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.58, p
      < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27-0.64, p < 0.001), distant
      metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23-0.58, p < 0.001) and local
      regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25-0.73, p = 0.002).
      Multivariate analysis showed that TILs are an independent prognostic indicator
      for DFS in all cohorts. In summary, this study indicated that TILs may reflect
      the immunological heterogeneity of NPC and could represent a new prognostic
      biomarker.

PMID- 29377122
TI  - Effect of l-caldesmon on osteoclastogenesis in RANKL-induced RAW264.7 cells.
AB  - Non-muscle caldesmon (l-CaD) is involved in the regulation of actin cytoskeletal
      remodeling in the podosome formation, but its function in osteoclastogenesis
      remains to be determined. In this study, RANKL-induced differentiation of
      RAW264.7 murine macrophages to osteoclast-like cells (OCs) was used as a model to
      determine the physiological role of l-CaD and its phosphorylation in
      osteoclastogenesis. Upon RANKL treatment, RAW264.7 cells undergo cell-cell fusion
      into multinucleate, and TRAP-positive large OCs with a concomitant increase of l
      CaD expression. Using gain- and loss-of-function in OC precursor cells followed
      by RANKL induction, we showed that the expression of l-CaD in response to RANKL
      activation is an important event for osteoclastogenesis, and bone resorption. To
      determine the effect of l-CaD phosphorylation in osteoclastogenesis, three decoy
      peptides of l-CaD were used with, respectively, Ser-to-Ala mutations at the Erk-
      and Pak1-mediated phosphorylation sites, and Ser-to-Asp mutation at the Erk
      mediated phosphorylation sites. Both the former two peptides competed with the C
      terminal segment of l-CaD for F-actin binding and accelerated formation of
      podosome-like structures in RANKL-induced OCs, while the third peptide did not
      significantly affect the F-actin binding of l-CaD, and decreased the formation of
      podosome-like structures in OCs. With the experiments using dephosphorylated and
      phosphorylated l-CaD mutants, we further showed that dephosphorylated l-CaD
      mutant facilitated RANKL-induced TRAP activity with an increased cell fusion
      index, whereas phosphorylated l-CaD decreased the TRAP activity and cell fusion.
      Our findings suggested that both the level of l-CaD expression and the extent of
      l-CaD phosphorylation play a role in RANKL-induced osteoclast differentiation.

PMID- 29377123
TI  - Effects of bone marrow mesenchymal stem cells transfected with Ang-1 gene on
      hyperoxia-induced optic nerve injury in neonatal mice.
AB  - Optic nerve injury triggered retinal ganglion cell (RGC) death and optic nerve
      atrophy lead to visual loss. Bone marrow mesenchymal stem cells (BMSCs) are
      stromal cells, capable of proliferating and differentiating into different types
      of tissues. This aims of this study is to investigate the role of BMSCs
      transfected with angiopoietin-1 (Ang-1) in optic nerve injury induced by
      hyperoxia in a neonatal mice model. Ang-1 overexpression vector was constructed
      and used to transfect BMSCs. Reverse transcription-quantitative polymerase chain
      reaction was performed to detect Ang-1 expression in BMSCs. The hyperoxia-induced
      optic nerve injury model was established. The optic nerves at 6-7 mm posterior to
      the eyeball were extracted, and were treated with luxol fast blue staining,
      immunohistochemistry, immunofluorescence, and transmission electron microscopy to
      examine the effects of Ang-1-modified BMSCs on optic nerve injury induced by
      hyperoxia. The mice in the Ang-1 + BMSCs and BMSCs groups showed remarkably
      improved myelin sheaths of nerve fibers compared to the hyperoxia saline group.
      The positive expression and integrated optic density of Ang-1 in the Ang-1 +
      BMSCs group were significantly higher compared to the air control, hyperoxia
      saline and BMSCs groups. The number and diameter of myelinated nerve fibers, the
      diameter of axons and the thickness of myelin sheath in the air control and Ang-1
      + BMSCs groups were higher compared to the hyperoxia saline group. Our study
      provides evidence supporting that Ang-1-modified BMSCs may have preventive and
      therapeutic effects on hyperoxia-induced optic nerve injury in neonatal mice.

PMID- 29377125
TI  - Estimating the effective number of breeders from single parr samples for
      conservation monitoring of wild populations of Atlantic salmon Salmo salar.
AB  - This study assesses whether the effective number of breeders (Nb ) can be
      estimated using a time and cost-effective protocol using genetic sibship
      reconstruction from a single sample of young-of-the-year (YOY) for the purposes
      of Atlantic salmon Salmo salar population monitoring. Nb was estimated for 10
      consecutive reproductive seasons for S. salar in the River Nivelle, a small
      population located at the rear-edge of the species distribution area in France,
      chronically under its conservation limit and subjected to anthropogenic and
      environmental changes. Subsampling of real and simulated data showed that
      accurate estimates of Nb can be obtained from YOY genotypes, collected at
      moderate random sampling intensity, achievable using routine juvenile
      electrofishing protocols. Spatial bias and time elapsed since spawning were found
      to affect estimates, which must be accounted for in sampling designs. Nb
      estimated in autumn for S. salar in the River Nivelle was low and variable across
      years from 23 (95% C.I. 14-41) to 75 (53-101) and was not statistically
      correlated with the estimated number of returning adults, but it was positively
      correlated with the estimated number of YOY at age 9 months. Nb was found to be
      lower for intermediate levels of redd aggregation, suggesting that the strength
      of the competition between males to access females affects reproductive success
      variance depending on redd spatial configuration. Thus, environmental factors
      such as habitat availability and quality for spawning and YOY development
      predominate over demographic ones (number of returning adults) in driving long
      term population viability for S. salar in the River Nivelle. This study showcases
      Nb as an integrated parameter, encompassing demographic and ecological
      information about a reproductive event, relevant to the assessment of both short
      term effects of management practices and long-term population conservation
      status.

PMID- 29377126
TI  - Sphingosine 1-phosphate receptors regulate TLR4-induced CXCL5 release from
      astrocytes and microglia.
AB  - Sphingosine 1-phosphate receptors (S1PR) are G protein-coupled and compose a
      family with five subtypes, S1P1R-S1P5R. The drug Gilenya(r) (Novartis, Basel,
      Switzerland) (Fingolimod; FTY720) targets S1PRs and was the first oral therapy
      for patients with relapsing-remitting multiple sclerosis (MS). The phosphorylated
      form of FTY720 (pFTY720) binds S1PRs causing initial agonism, then subsequent
      receptor internalization and functional antagonism. Internalization of S1P1R
      attenuates sphingosine 1-phosphate (S1P)-mediated egress of lymphocytes from
      lymph nodes, limiting aberrant immune function in MS. pFTY720 also exerts direct
      actions on neurons and glial cells which express S1PRs. In this study, we
      investigated the regulation of pro-inflammatory chemokine release by S1PRs in
      enriched astrocytes and microglial cultures. Astrocytes and microglia were
      stimulated with lipopolysaccharide (LPS) and increases in C-X-C motif chemokine 5
      (CXCL5), also known as LIX (lipopolysaccharide-induced CXC chemokine) expression
      were quantified. Results showed that pFTY720 attenuated LPS-induced CXCL5 (LIX)
      protein release from astrocytes, as did the S1P1R selective agonist, SEW2871. In
      addition, pFTY720 blocked messenger ribonucleic acid (mRNA) transcription of the
      chemokines, (i) CXCL5/LIX, (ii) C-X-C motif chemokine 10 (CXCL10) also known as
      interferon gamma-induced protein 10 (IP10) and (iii) chemokine (C-C motif) ligand
      2 (CCL2) also known as monocyte chemoattractant protein 1 (MCP1). Interestingly,
      inhibition of sphingosine kinase attenuated LPS-induced increases in mRNA levels
      of all three chemokines, suggesting that LPS-TLR4 (Toll-like receptor 4)
      signalling may enhance chemokine expression via S1P-S1PR transactivation. Lastly,
      these observations were not limited to astrocytes since we also found that
      pFTY720 attenuated LPS-induced release of CXCL5 from microglia. These data
      highlight a role for S1PR signalling in regulating the levels of chemokines in
      glial cells and support the notion that pFTY720 efficacy in multiple sclerosis
      may involve the direct modulation of astrocytes and microglia.

PMID- 29377124
TI  - Purinergic signaling in oligodendrocyte development and function.
AB  - Myelin, an insulating membrane that enables rapid action potential propagation,
      is an essential component of an efficient, functional vertebrate nervous system.
      Oligodendrocytes, the myelinating glia of the central nervous system (CNS),
      produce myelin throughout the CNS, which requires continuous proliferation,
      migration, and differentiation of oligodendrocyte progenitor cells. Because
      myelination is essential for efficient neurotransmission, researchers hypothesize
      that neuronal signals may regulate the cascade of events necessary for this
      process. The ability of oligodendrocytes and oligodendrocyte progenitor cells to
      detect and respond to neuronal activity is becoming increasingly appreciated,
      although the specific signals involved are still a matter of debate. Recent
      evidence from multiple studies points to purinergic signaling as a potential
      regulator of oligodendrocyte development and differentiation. Adenosine
      triphosphate (ATP) and its derivatives are potent signaling ligands with
      receptors expressed on many populations of cells in the nervous system, including
      cells of the oligodendrocyte lineage. Release of ATP into the extracellular space
      can initiate a multitude of signaling events, and these downstream signals are
      specific to the particular purinergic receptor (or receptors) expressed, and
      whether enzymes are present to hydrolyze ATP to its derivatives adenosine
      diphosphate and adenosine, each of which can activate their own unique downstream
      signaling cascades. This review will introduce purinergic signaling in the CNS
      and discuss evidence for its effects on oligodendrocyte proliferation,
      differentiation, and myelination. We will review sources of extracellular purines
      in the nervous system and how changes in purinergic receptor expression may be
      coupled to oligodendrocyte differentiation. We will also briefly discuss
      purinergic signaling in injury and diseases of the CNS.

PMID- 29377127
TI  - Dental therapists linked to improved dental outcomes for Alaska Native
      communities in the Yukon-Kuskokwim Delta.
AB  - OBJECTIVES: Dental Health Aide Therapists (DHATs) have been part of the dental
      workforce in Alaska's Yukon-Kuskokwim (YK) Delta since 2006. They are trained to
      provide preventive and restorative care such as filling and extractions. In this
      study, we evaluated community-level dental outcomes associated with DHATs.
      METHODS: This was a secondary data analysis of Alaska Medicaid and electronic
      health record data for individuals in Alaska's YK Delta (2006-2015). The
      independent variable was the number of DHAT treatment days in each community.
      Child outcomes were preventive care, extractions, and general anesthesia. Adult
      outcomes were preventive care and extractions. We estimated Spearman partial
      correlation coefficients to test our hypotheses that increased DHAT treatment
      days would be associated with larger proportions utilizing preventive care and
      smaller proportions receiving extractions at the community-level. RESULTS: DHAT
      treatment days were positively associated with preventive care utilization and
      negatively associated with extractions for children and adults (P < 0.0001). DHAT
      treatment days were not associated with increased dental treatment under general
      anesthesia for children. CONCLUSIONS: Dental therapists are associated with more
      preventive care and fewer extractions. State-level policies should consider
      dental therapists as part of a comprehensive solution to meet the dental care
      needs of individuals in underserved communities and help achieve health equity
      and social justice.

PMID- 29377128
TI  - The Effect of Lowering the Legal Drink-Drive Limit on the Toxicological Findings
      in Driver Fatalities: A Comparison of Two Jurisdictions.
AB  - In December 2014, the legal blood alcohol limit for drivers in both Scotland and
      New Zealand was reduced from 80 to 50 mg/100 mL. This paper reports a
      retrospective study comparing changes in the toxicological findings in deceased
      drivers and motorcyclists before and after the limit change in both
      jurisdictions. A year of fatal motor vehicle crashes prior to and following the
      limit change is examined for both countries. In Scotland, there was an increase
      in drug prevalence among fatally injured drivers and motorcyclists, with the use
      of all drug groups increasing after the limit change, with the exception of
      cannabinoids. In New Zealand, there was a reduction in cases involving drugs
      only, but increases in the numbers of deceased drivers and motorcyclists positive
      for alcohol only and co-using alcohol and drugs.

PMID- 29377129
TI  - Is high-grade prostatic intraepithelial neoplasia (HGPIN) a reliable precursor
      for prostate carcinoma? Implications for clonal evolution and early detection
      strategies.
AB  - High-grade prostatic intraepithelial neoplasia (HGPIN) is a documented putative
      precursor lesion for invasive prostate adenocarcinoma. However, the precise
      mechanisms of the carcinoma's development from HGPIN are unclear. Many studies
      have attempted a comparative molecular genetic characterisation of HGPIN and its
      corresponding carcinoma to study this transformation. However, to date, some
      HGPIN mimickers, such as intraductal carcinoma, which can engage in retrograde
      colonisation of the prostatic acini in an HGPIN-like manner, have been described.
      In this work, we hypothesise that the lesion formerly known as HGPIN adjacent to
      invasive carcinoma does not necessarily represent its respective precursor
      lesion. This hypothesis stems from recent morphological, experimental, and
      theoretical evidence on the development of tumour clonality, as well as recent
      studies outlining the three-dimensional architecture of prostate adenocarcinomas
      (most importantly, their interconnection with the tumoural glandular system).
      Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 29377130
TI  - The microbiome and cancer.
AB  - Humans coexist with a vast bacterial, fungal and viral microbiome with which we
      have coevolved for millions of years. Several long recognized epidemiological
      associations between particular bacteria and cancer are now understood at the
      molecular level. At the same time, the arrival of next-generation sequencing
      technology has permitted a thorough exploration of microbiomes such as that of
      the human gut, enabling observation of taxonomic and metabolomic relationships
      between the microbiome and cancer. These studies have revealed causal mechanisms
      for both microbes within tumours and microbes in other host niches separated from
      tumours, mediated through direct and immunological mechanisms. Copyright (c) 2018
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 29377131
TI  - Accuracy of international classification of diseases, ninth revision, codes for
      postpartum hemorrhage among women undergoing cesarean delivery.
AB  - BACKGROUND: Determining the accuracy of International Classification of Diseases,
      Ninth Revision, Clinical Modification (ICD-9) codes for postpartum hemorrhage
      (PPH) is vital for reaching valid conclusions about the epidemiology of PPH. Our
      primary objectives were to assess the performance characteristics of ICD-9 PPH
      codes against a reference standard using estimated blood loss (EBL) among a
      cohort undergoing Cesarean delivery. STUDY DESIGN AND METHODS: We analyzed
      maternal discharge and EBL data from women who underwent Cesarean delivery at
      Kaiser Permanente Northern California facilities between 2010 and 2013. We
      defined PPH as an EBL of at least 1000 mL. In a secondary analysis, ICD-9
      performance characteristics were assessed using an EBL of at least 1500 mL to
      classify severe PPH. RESULTS: We identified 35,614 hospitalizations for Cesarean
      delivery. Using EBL of at least 1000 mL as the "gold standard," PPH codes had a
      sensitivity of 27.8%, specificity of 97%, positive predictive value (PPV) of
      74.5%, and a negative predictive value (NPV) of 80.9%. The prevalence of a PPH
      code (9%) was lower than the prevalence using a blood loss of at least 1000 mL
      (24%). Using a reference standard of EBL of at least 1500 mL, PPH codes had a
      sensitivity of 61.7%, specificity of 93.8%, PPV of 34.2%, and NPV of 97.9%.
      CONCLUSION: PPH ICD-9 codes have high specificity, moderately high PPVs and NPVs,
      and low sensitivity. An EBL of at least 1500 mL as a reference standard has
      higher sensitivity. Our findings suggest that, for women undergoing Cesarean
      delivery, quality improvement efforts are needed to enhance PPH ICD-9 coding
      accuracy in administrative data sets.

PMID- 29377133
TI  - Reviewer selection biases editorial decisions on manuscripts.
AB  - Many journals, including the Journal of Neurochemistry, enable authors to list
      peer reviewers as 'preferred' or 'opposed' suggestions to the editor. At the
      Journal of Neurochemistry, the handling editor (HE) may follow recommendations or
      select non-author-suggested reviewers (non-ASRs). We investigated whether
      selection of author-suggested reviewers (ASRs) influenced decisions on a paper,
      and whether differences might be related to a reviewer's, editor's or
      manuscript's geographical location. In this retrospective analysis, we compared
      original research articles submitted to the Journal of Neurochemistry from 2013
      through 2016 that were either reviewed exclusively by non-ASRs, by at least one
      ASR, by at least one reviewer marked by the author as 'opposed' or none.
      Manuscript outcome, reviewer rating of manuscript quality, rating of the
      reviewers' performance by the editor (R-score), time to review, and the country
      of the editor, reviewers and manuscript author were analyzed using non-parametric
      rank-based comparisons, chi-square (chi2 ) analysis, multivariate linear
      regression, one-way analysis of variance, and inter-rater reliability
      determination. Original research articles that had been reviewed by at least one
      ASR stood a higher chance of being accepted (525/1006 = 52%) than papers that had
      been reviewed by non-ASRs only (579/1800 = 32%). An article was 2.4 times more
      likely to be accepted than rejected by an ASR compared to a non-ASR (Pearson's
      chi2 (1) = 181.3, p < 0.05). At decision, the editor did not simply follow the
      reviewers' recommendation but had a balancing role: Rates of recommendation from
      reviewers for rejection were 11.2% (139/1241) with ASRs versus 29.0% (1379/4755)
      with non-ASRs (this is a ratio of 0.39 where 1 means no difference between
      rejection rates for both groups), whereas the proportion of final decisions to
      reject was 24.7% (248/1006) versus 45.7% (822/1800) (a ratio of 0.54,
      considerably closer to 1). Recommendations by non-ASRs were more favorable for
      manuscripts from USA/Canada and Europe than for Asia/Pacific or Other countries.
      ASRs judged North American manuscripts most favorably, and judged papers
      generally more positively (mean: 2.54 on a 1-5 scale) than did non-ASRs (mean:
      3.16) reviewers, whereas time for review (13.28 vs. 13.20 days) did not differ
      significantly between these groups. We also found that editors preferably
      assigned reviewers from their own geographical region, but there was no tendency
      for reviewers to judge papers from their own region more favorably. Our findings
      strongly confirm a bias toward lower rejection rates when ASRs assess a paper,
      which led to the decision to abandon the option to recommend reviewers at the
      Journal of Neurochemistry. Open Data: Materials are available on
      https://osf.io/jshg7/.

PMID- 29377132
TI  - Never at rest: insights into the conformational dynamics of ion channels from
      cryo-electron microscopy.
AB  - The tightly regulated opening and closure of ion channels underlies the
      electrical signals that are vital for a wide range of physiological processes.
      Two decades ago the first atomic level view of ion channel structures led to a
      detailed understanding of ion selectivity and conduction. In recent years,
      spectacular developments in the field of cryo-electron microscopy have resulted
      in cryo-EM superseding crystallography as the technique of choice for determining
      near-atomic resolution structures of ion channels. Here, we will review the
      recent developments in cryo-EM and its specific application to the study of ion
      channel gating. We will highlight the advantages and disadvantages of the current
      technology and where the field is likely to head in the next few years.

PMID- 29377134
TI  - Critical role of rabphilin-3A in the pathophysiology of experimental lymphocytic
      neurohypophysitis.
AB  - Autoimmune hypophysitis (AH) is thought to be an autoimmune disease characterized
      by lymphocytic infiltration of the pituitary gland. Among AH pathologies,
      lymphocytic infundibulo-neurohypophysitis (LINH) involves infiltration of the
      neurohypophysis and/or the hypothalamic infundibulum, causing central diabetes
      insipidus resulting from insufficiency of arginine vasopressin secretion. The
      pathophysiological and pathogenetic mechanisms underlying LINH are largely
      unknown. Clinically, differentiating LINH from other pituitary diseases
      accompanied by mass lesions, including tumours, has often been difficult, because
      of similar clinical manifestations. We recently reported that rabphilin-3A is an
      autoantigen and that anti-rabphilin-3A antibodies constitute a possible
      diagnostic marker for LINH. However, the involvement of rabphilin-3A in the
      pathogenesis of LINH remains to be elucidated. This study was undertaken to
      explore the role of rabphilin-3A in lymphocytic neurohypophysitis and to
      investigate the mechanism. We found that immunization of mice with rabphilin-3A
      led to neurohypophysitis. Lymphocytic infiltration was observed in the
      neurohypophysis and supraoptic nucleus 1 month after the first immunization. Mice
      immunized with rabphilin-3A showed an increase in the volume of urine that was
      hypotonic as compared with control mice. Administration of a cocktail of
      monoclonal anti-rabphilin-3A antibodies did not induce neurohypophysitis.
      However, abatacept, which is a chimeric protein that suppresses T-cell
      activation, decreased the number of T cells specific for rabphilin-3A in
      peripheral blood mononuclear cells (PBMCs). It ameliorated lymphocytic
      infiltration of CD3+ T cells in the neurohypophysis of mice that had been
      immunized with rabphilin-3A. Additionally, there was a linear association between
      the number of T cells specific for rabphilin-3A in PBMCs and the number of CD3+ T
      cells infiltrating the neurohypophysis. In conclusion, we suggest that rabphilin
      3A is a pathogenic antigen, and that T cells specific for rabphilin-3A are
      involved in the pathogenesis of neurohypophysitis in mice. Copyright (c) 2018
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 29377135
TI  - Supporting young researchers in food texture studies.
AB  - : I learned about food texture by reading many articles in the Journal of Texture
      Studies (JTS) and Prof. Bourne's textbook Food Texture and Viscosity, Concept and
      Measurement. I present here his great contributions as both the Editor-in-Chief
      of JTS and as the author of a superior textbook in the cultivation of future food
      texture researchers. Prof. Bourne has provided significant guidance to those in
      the industry using his textbook to suggest appropriate approaches to measure,
      evaluate, and alter the textures of agro-products and processed foods. I began my
      career in food rheology, learned the physiological techniques necessary for
      measuring mastication, and developed relationships with good sensory scientists
      along the way. I am happy to offer advice to agriculture and food scientists,
      researchers, and engineers in the food industry regarding food texture. I would
      like to be a follower of Prof. Bourne and support young food texture scientists
      in the 21st century. PRACTICAL APPLICATIONS: Food texture studies conducted
      during the last century are beginning to evolve. Based on previous publications
      in the Journal of Texture Studies, I believe that several areas can be further
      examined in this century. First, methods to evaluate the textures of
      heterogeneous materials, such as fruits and vegetables, require improvements.
      Second, the monitoring of rapid changes in food texture during oral processing
      should be considered during the design of food products. Third, a new
      instrumental method that mimics the movement and breakdown of soft foods by the
      tongue is being developed. The optimization of food processing to reduce the loss
      of agro-products and production of high-quality foods both require more attention
      according to the Sustainable Development Goals adopted by the United Nations in
      2015.

PMID- 29377136
TI  - Characterization and differentiation of sheep's milk from Greek breeds based on
      physicochemical parameters, fatty acid composition and volatile profile.
AB  - BACKGROUND: There are only limited studies in the literature attempting to
      differentiate sheep's milk originating from different sheep breeds. In the
      present study the physicochemical parameters (pH, percent fat, percent protein,
      percent lactose and percent total solids), fatty acid composition and volatile
      profile of raw milk from four autochthonous Greek breeds (Karagouniko, Mpoutsiko,
      Artas and Chios) were determined. The objective of the present study was to
      characterize and differentiate the sheep breeds based on the above analytical
      parameters in combination with chemometrics. RESULTS: The overall correct
      classification rate was 79.7%%, 84.4% and 100% based on physicochemical
      parameters, fatty acid composition and volatile profile, respectively. Volatiles
      proved to be the most effective of parameters analyzed for the differentiation of
      sheep breed. Furthermore, the combination of physicochemical parameters and fatty
      acid composition gave a correct classification rate equal to 96.9%. CONCLUSION:
      Either volatile profile or the combination of physicochemical parameters and
      fatty acid composition may be easily determined and used for the differentiation
      of sheep's milk from four different Greek breeds, this being the novelty of the
      present work. This may be very important in terms of PDO (Protected Designation
      of Origin) and PGI (Protected Geographical Indication) products related to
      specific geographical origin and sensory characteristics. (c) 2018 Society of
      Chemical Industry.

PMID- 29377137
TI  - Rab 10-a traffic controller in multiple cellular pathways and locations.
AB  - Rab GTPases are key regulators of eukaryotic membrane traffic, and their
      functions and activities are limited to particular intracellular transport steps
      and their membrane localization is by and large restricted. Some Rabs do
      participate in more than one transport steps, but broadly speaking, there is a
      clear demarcation between exocytic and endocytic Rabs. One Rab protein, Rab10,
      however, appears to be anomalous in this regard and has a diverse array of
      functions and subcellular localizations. Rab10 has been implicated in a myriad of
      activities ranging from polarized exocytosis and endosomal sorting in polarized
      cells, insulin-dependent Glut4 transport in adipocytes, axonal growth in neurons,
      and endo-phagocytic processes in macrophages. It's reported subcellular
      localizations include the endoplasmic reticulum (ER), Golgi/TGN, the
      endosomes/phagosomes and the primary cilia. In this review, we summarize and
      discuss the multitude of known roles of Rab10 in cellular membrane transport and
      the molecular players and mechanisms associated with these roles.

PMID- 29377138
TI  - Utility of zinc protoporphyrin in management of whole blood donors.
AB  - BACKGROUND: Deferral for low hemoglobin (Hb) increases the likelihood that donors
      do not return for future donations. Zinc protoporphyrin (ZPP) has been described
      as a sensitive marker of iron-deficient erythropoiesis, before Hb decreases. It
      is a relatively cheap, rapid, and easy-to-perform measurement in a drop of whole
      blood. To assess the utility of ZPP measurement in donor management we examined
      whether ZPP and Hb levels among first-time donors differ from repeat donors. We
      further explored whether ZPP increases over subsequent donations at a donor
      population level and whether increasing ZPP levels coincide with decreasing Hb
      levels and donor deferral. STUDY DESIGN AND METHODS: We included first-time (n =
      4983) and repeat (n = 3533) whole blood donors from the ZPP and Iron in the
      Netherlands Cohort (ZINC) study. ZPP and Hb were measured at each subsequent
      donation during a 4-year period after inclusion in the study. RESULTS: Median ZPP
      levels were higher in repeat than in first-time donors. In first-time donors,
      especially women, ZPP levels were increased with a corresponding decline in Hb
      levels over subsequent donations. ZPP levels were increased among first-time
      donors deferred for low Hb. CONCLUSION: Our results suggest that adding ZPP to Hb
      measurements in the daily blood collection setting, especially for first-time
      donors and first-time female donors may add to the identification of a donor
      subpopulation with low functional iron stores.

PMID- 29377139
TI  - Late-onset Becker-type muscular dystrophy in a Border terrier dog.
AB  - A 9-year-old Border terrier was presented to a referral hospital after a 1-year
      history of progressive stiffness and exercise intolerance. Neurological
      examination was consistent with a neuromuscular disorder. Serum creatine kinase
      activity was mildly elevated. A myopathy was suspected based on MRI findings and
      electrophysiological examination. Muscle histopathology was consistent with a
      severe non-inflammatory myopathy of a dystrophic type. Immunofluorescence and
      western blotting confirmed a dystrophinopathy with an 80-kDa truncated dystrophin
      fragment similar to Becker muscular dystrophy in people. To our knowledge, this
      is the first description of a late-onset Becker-type muscular dystrophy in a dog,
      and the first description of a dystrophinopathy in a Border terrier. Muscular
      dystrophy in dogs should not be ruled out based on late onset clinical signs and
      only mildly elevated creatine kinase.

PMID- 29377140
TI  - Patterns of diversity, endemism and specialization in the root symbiont
      communities of alder species on the island of Corsica.
AB  - We investigated whether the diversity, endemicity and specificity of alder
      symbionts could be changed by isolation in a Mediterranean glacial refugium. We
      studied both ectomycorrhizal (EM) fungi and nitrogen-fixing actinobacteria
      associated with alders, and compared their communities in Corsica and on the
      European continent. Nodules and root tips were sampled on the three alder species
      present in Corsica and continental France and Italy. Phylogenies based on
      internal transcribed spacer (ITS) and a multilocus sequence analysis approach
      were used to characterize fungal and Frankia species, respectively. Patterns of
      diversity, endemism and specialization were compared between hosts and regions
      for each symbiont community. In Corsica, communities were not generally richer
      than on the mainland. The species richness per site depended mainly on host
      identity: Alnus glutinosa and Alnus cordata hosted richer Frankia and EM
      communities, respectively. Half of the Frankia species were endemic to Corsica
      against only 4% of EM species. Corsica is not a hotspot of diversity for all
      alder symbionts but sustains an increased frequency of poor-dispersers such as
      hypogeous fungi. Generalist EM fungi and host-dependent profusely sporulating
      (Sp+) Frankia were abundantly associated with Corsican A. cordata, a pattern
      related to a more thermophilic and xerophylic climate and to the co-occurrence
      with other host trees.

PMID- 29377141
TI  - Evaluation of HPV type-replacement in unvaccinated and vaccinated adolescent
      females-Post-hoc analysis of a community-randomized clinical trial (II).
AB  - Efficacy of human papillomavirus (HPV) vaccines promises to control HPV
      infections. However, HPV vaccination programs may lay bare an ecological niche
      for non-vaccine HPV types. We evaluated type-replacement by HPV type and
      vaccination strategy in a community-randomized trial executed in HPV vaccination
      naive population. Thirty-three communities were randomized to gender-neutral
      vaccination with AS04-adjuvanted HPV16/18 vaccine (Arm A), HPV vaccination of
      girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral
      HBV vaccination (Arm C). Resident 1992-95 born boys (40,852) and girls (39,420)
      were invited. 11,662 boys and 20,513 girls were vaccinated with 20-30% and 45-48%
      coverage, respectively. HPV typing of 11,396 cervicovaginal samples was performed
      by high throughput PCR. Prevalence ratios (PR) between arms and ranked order of
      HPV types and odds ratio (OR) for having multiple HPV types in HPV16 or 18/45
      positive individuals were calculated. The ranked order of HPV types did not
      significantly differ between arms or birth cohorts. For the non-HPV vaccinated
      1992-1993 birth cohorts increased PR, between the gender-neutral intervention
      versus control arms for HPV39 (PRA 1.84, 95% CI 1.12-3.02) and HPV51 (PRA 1.56,
      95% CI 1.11-2.19) were observed. In the gender-neutral arm, increased clustering
      between HPV39 and the vaccine-covered HPV types 16 or 18/45 (ORA16  = 5.1,
      ORA18/45  = 11.4) was observed in the non-HPV vaccinated 1994-1995 birth cohorts.
      Comparable clustering was seen between HPV51 and HPV16 or HPV18/45 (ORB16  = 4.7,
      ORB18/45  = 4.3), in the girls-only arm. In conclusion, definitively consistent
      postvaccination patterns of HPV type-replacement were not observed. Future
      occurrence of HPV39 and HPV51 warrant investigation.

PMID- 29377143
TI  - Socioeconomic and behavioral determinants of tooth brushing frequency: results
      from the representative French 2010 HBSC cross-sectional study.
AB  - OBJECTIVES: To describe tooth brushing frequency and its association with a wide
      range of socioeconomic and behavioral characteristics, using a nationally
      representative sample of school-aged children in France. METHODS: Our sample
      included 11,337 students aged from 10 to 16 years, who answered the HBSC
      questionnaire. Some variables were grouped into composite variables, thus
      generating scores for: eating habits, health and body, relationships with
      parents, socioeconomic status (SES) of family, and school life. Multivariate
      logistic regression analyses were used to study the relationship between these
      variables and tooth brushing frequency. RESULTS: Girls were more likely to brush
      twice a day than boys [adjusted Odds Ratio: aOR 2.47, 95 percent confidence
      interval CI95% (1.97; 3.11), aOR 1.89, CI95% (1.56; 2.29), aOR 1.45, CI95% (1.25;
      1.68) for low, mid, and high school life score, respectively]. Students were more
      likely to brush twice a day when they had high (versus low) scores for healthy
      eating habits [aOR = 1.60; 95 percent CI: (1.40; 1.83)], well-being concerning
      health and body [aOR = 1.61; 95 percent CI: (1.40; 1.86)] and SES [aOR = 1.25; 95
      percent CI: (1.09; 1.43)]. CONCLUSIONS: We believe that preventive health
      campaigns should target school and family environments more specifically to reach
      the most disadvantaged sections of the population and include promotion of whole
      health. The messages should be designed to efficiently reach adolescents, e.g.,
      by appealing to their maturity, self-esteem, and emotional factors. Through the
      incorporation of qualitative research elements, identifying the reasons for not
      brushing twice a day would also help to develop new prevention programs.

PMID- 29377142
TI  - Mechanisms linking T-wave alternans to spontaneous initiation of ventricular
      arrhythmias in rabbit models of long QT syndrome.
AB  - KEY POINTS: T-wave alternans (TWA) and T-wave lability (TWL) are precursors of
      ventricular arrhythmias in long QT syndrome; however, the mechanistic link
      remains to be clarified. Computer simulations show that action potential duration
      (APD) prolongation and slowed heart rates promote APD alternans and chaos,
      manifesting as TWA and TWL, respectively. Regional APD alternans and chaos can
      exacerbate pre-existing or induce de novo APD dispersion, which combines with
      enhanced ICa,L to result in premature ventricular complexes (PVCs) originating
      from the APD gradient region. These PVCs can directly degenerate into re-entrant
      arrhythmias without the need for an additional tissue substrate or further
      exacerbate the APD dispersion to cause spontaneous initiation of ventricular
      arrhythmias. Experiments conducted in transgenic long QT rabbits show that PVC
      alternans occurs at slow heart rates, preceding spontaneous intuition of
      ventricular arrhythmias. ABSTRACT: T-wave alternans (TWA) and irregular beat-to
      beat T-wave variability or T-wave lability (TWL), the ECG manifestations of
      action potential duration (APD) alternans and variability, are precursors of
      ventricular arrhythmias in long QT syndromes. TWA and TWL in patients tend to
      occur at normal heart rates and are usually potentiated by bradycardia. Whether
      or how TWA and TWL at normal or slow heart rates are causally linked to
      arrhythmogenesis remains unknown. In the present study, we used computer
      simulations and experiments of a transgenic rabbit model of long QT syndrome to
      investigate the underlying mechanisms. Computer simulations showed that APD
      prolongation and slowed heart rates caused early afterdepolarization-mediated APD
      alternans and chaos, manifesting as TWA and TWL, respectively. Regional APD
      alternans and chaos exacerbated pre-existing APD dispersion and, in addition, APD
      chaos could also induce APD dispersion de novo via chaos desynchronization.
      Increased APD dispersion, combined with substantially enhanced ICa,L , resulted
      in a tissue-scale dynamical instability that gave rise to the spontaneous
      occurrence of unidirectionally propagating premature ventricular complexes (PVCs)
      originating from the APD gradient region. These PVCs could directly degenerate
      into re-entrant arrhythmias without the need for an additional tissue substrate
      or could block the following sinus beat to result in a longer RR interval, which
      further exacerbated the APD dispersion giving rise to the spontaneous occurrence
      of ventricular arrhythmias. Slow heart rate-induced PVC alternans was observed in
      experiments of transgenic LQT2 rabbits under isoproterenol, which was associated
      with increased APD dispersion and spontaneous occurrence of ventricular
      arrhythmias, in agreement with the theoretical predictions.

PMID- 29377144
TI  - Are the benefits of autonomy satisfaction and the costs of autonomy frustration
      dependent on individuals' autonomy strength?
AB  - OBJECTIVE: From a self-determination theory perspective, individuals are assumed
      to benefit and suffer from, respectively, the satisfaction and frustration of the
      psychological need for autonomy, even if they score low on autonomy strength.
      Yet, previous studies on need strength are scarce, operationalized need strength
      differently, and produced inconsistent findings. METHOD: In two studies among 224
      South African adults (Mage  = 24.13, SD = 4.25; 54.0% male) and 156 Belgian
      prisoners (Mage  = 38.60, SD = 11.68; 88.5% male), we investigated the moderating
      role of autonomy valuation and desire in the relations of autonomy satisfaction
      and frustration with a variety of well-being and ill-being indicators. RESULTS:
      Study 1 provided some evidence for the moderating role of mostly explicit
      autonomy desire (rather than explicit autonomy valuation). In Study 2, neither
      explicit nor implicit autonomy desire played a consistent moderating role.
      CONCLUSIONS: Overall, these findings are congruent with a moderate (albeit not
      with a strong) interpretation of the universality claim made within self
      determination theory, provide initial evidence for a differentiation between
      deficit-based and growth-oriented interpersonal differences in need strength, and
      indicate that the potential moderating role of need strength deserves continued
      attention before any firm conclusions can be drawn.

PMID- 29377145
TI  - Autosomal recessive congenital cataract in captive-bred vervet monkeys
      (Chlorocebus aethiops).
AB  - BACKGROUND: The aim of the study was to evaluate the genetic predisposition of
      congenital cataract in a colony of captive-bred vervet monkeys. METHODS: Four
      congenital cataract genes: glucosaminyl (N-acetyl) transferase 2 (GCNT2), heat
      shock transcription factor 4 (HSF4), crystallin alpha A (CRYAA) and lens
      intrinsic membrane protein-2 (LIM2) were screened, sequenced and analysed for
      possible genetic variants in 36 monkeys. Gene expression was also evaluated in
      these genes. RESULTS: Fifteen sequence variants were identified in the coding
      regions of three genes (GCNT2, HSF4 and CRYAA). Of these variations, only three
      were missense mutations (M258V, V16I and S24N) and identified in the GCNT2
      transcripts A, B and C, respectively, which resulted in a downregulated gene
      expression. CONCLUSION: Although the three missense mutations in GCNT2 have a
      benign effect, a possibility exists that the candidate genes (GCNT2, HSF4 and
      CRYAA) might harbour mutations that are responsible for total congenital
      cataract.

PMID- 29377146
TI  - Brasilonema lichenoides sp. nov. and Chroococcidiopsis lichenoides sp. nov.
      (Cyanobacteria): two novel cyanobacterial constituents isolated from a tripartite
      lichen of headstones.
AB  - Cyanolichens are an assemblage of fungi and cyanobacteria from diverse,
      cosmopolitan habitats. Typically composed of a single species of cyanobacterium,
      with or without another eukaryotic alga, here we present two novel cyanobionts
      isolated from an undescribed tripartite lichen. This endolithic lichen was
      isolated from a granite cemetery tombstone from Jacksonville, FL, and contains
      two potentially nitrogen-fixing cyanobionts. Employing a total evidence approach,
      we characterized the cyanobionts using molecular (the 16S rDNA and ITS gene
      region), morphological, and ecological data. Phylogenetic analyses revealed two
      novel taxa: Brasilonema lichenoides and Chroococcidiopsis lichenoides, both of
      which fell within well-supported clades. To our knowledge, this represents the
      first instance of a tripartite lichen with two cyanobacterial and no eukaryotic
      members. These types of lichens may well represent an unexplored reservoir of
      cyanobacterial diversity. The specific epithets are proposed under the provisions
      of the International Code of Nomenclature for algae, fungi, and plants.

PMID- 29377147
TI  - The influence of Aloe vera gel incorporation on the physicochemical and
      mechanical properties of banana starch-chitosan edible films.
AB  - BACKGROUND: Aloe vera (AV) gel is a promising material in food conservation,
      given its widely reported antimicrobial and antioxidant activity; however, its
      application in the formation of edible films and coatings has been small owing
      its low film-forming capability. The aim of this study was to investigate the
      physicochemical properties of film-forming solutions and films prepared using
      unripe banana starch-chitosan and AV gel at different AV gel concentrations.
      RESULTS: Our results showed that AV gel considerably affected the rheological and
      optical properties of the edible coatings, mainly due to increased amounts of
      solids brought by the AV gel. Film-forming capacity and physicochemical
      properties were also studied; most of the film properties were affected by the
      inclusion of AV gel, with decreased water vapor permeability, tensile strength
      and elongation at break. Fourier transform infrared studies showed that the
      inclusion of AV gel disrupts the interaction between starch and chitosan
      molecules; however, further studies are needed to fully understand the specific
      interactions between the components of AV gel and both starch and chitosan
      molecules. CONCLUSION: Our results suggest that the addition of AV gel creates a
      crosslinking effect between the phenolic compounds in AV gel and starch
      molecules, which disrupts the starch-chitosan interaction and greatly affects the
      properties of both the film-forming solution and edible films. (c) 2018 Society
      of Chemical Industry.

PMID- 29377148
TI  - Framework for laboratory harmonization of folate measurements in low- and middle
      income countries and regions.
AB  - The measurement of serum and red blood cell folate, two commonly used biomarkers
      of folate status in populations, is complicated by analytical and data
      interpretation challenges. Folate results show poor comparability across
      laboratories, even using the same analytical technique. The folate microbiologic
      assay produces accurate results and requires simple instrumentation. Thus, it
      could be set up and maintained in low- and middle-income country laboratories.
      However, the assay has to be harmonized through the use of common critical
      reagents (e.g., microorganism and folate calibrator) in order to produce
      comparable results across laboratories and over time, so that the same cutoff
      values can be applied across surveys. There is a limited need for blood folate
      measurements in a country owing to the periodic nature of surveys. Having a
      network of regional resource laboratories proficient in conducting the folate
      microbiologic assay and willing and able to perform service work for other
      countries will be the most efficient way to create an infrastructure wherein
      qualified laboratories produce reliable blood folate data. Continuous
      participation of these laboratories in a certification program can verify and
      document their proficiency. If the resource laboratories conduct the work on a
      fee-for-service basis, they could become self-sustaining in the long run.

PMID- 29377151
TI  - Rationale for the clinical guidelines for myasthenia gravis in Japan.
AB  - According to the 2014 Japanese clinical guidelines for myasthenia gravis, the
      most important priority in treatment is maintaining patients' health-related
      quality of life. Therefore, the initial treatment goal is defined as maintaining
      a postintervention status of minimal manifestations or better (according to the
      Myasthenia Gravis Foundation of America classification) with an oral prednisolone
      dose of 5 mg/day or less. Every effort should be made to attain this level as
      rapidly as possible. To achieve this goal, the guidelines recommend minimizing
      the oral prednisolone dose, starting calcineurin inhibitors early in the course
      of treatment, using intravenous methylprednisolone infusion judiciously (often
      combined with plasma exchange/plasmapheresis or intravenous immunoglobulin), and
      effectively treating patients with an early, fast-acting treatment strategy. The
      early, fast-acting treatment strategy enables more frequent and earlier
      attainment of the initial goal than other strategies. Thymectomy is considered an
      option for treating nonthymomatous early-onset myasthenia gravis in patients with
      antiacetylcholine receptor antibodies and thymic hyperplasia in the early stages
      of the disease.

PMID- 29377150
TI  - Cardioprotective effects of dietary rapamycin on adult female C57BLKS/J-Leprdb
      mice.
AB  - Rapamycin (RAPA), an inhibitor of mTORC signaling, has been shown to extend life
      span in mice and other organisms. Recently, animal and human studies have
      suggested that inhibition of mTORC signaling can alleviate or prevent the
      development of cardiomyopathy. In view of this, we used a murine model of type 2
      diabetes (T2D), BKS-Leprdb , to determine whether RAPA treatment can mitigate the
      development of T2D-induced cardiomyopathy in adult mice. Female BKS-Leprdb mice
      fed diet supplemented with RAPA from 11 to 27 weeks of age showed reduced weight
      gain and significant reductions of fat and lean mass compared with untreated
      mice. No differences in plasma glucose or insulin levels were observed between
      groups; however, RAPA-treated mice were more insulin sensitive (P < 0.01) than
      untreated mice. Urine albumin/creatinine ratio was lower in RAPA-treated mice,
      suggesting reduced diabetic nephropathy and improved kidney function.
      Echocardiography showed significantly reduced left ventricular wall thickness in
      mice treated with RAPA compared with untreated mice (P = 0.02) that was
      consistent with reduced heart weight/tibia length ratios, reduced myocyte size
      and cardiac fibrosis measured by histomorphology, and reduced mRNA expression of
      Col1a1, a marker for cardiomyopathy. Our results suggest that inhibition of mTORC
      signaling is a plausible strategy for ameliorating complications of obesity and
      T2D, including cardiomyopathy.

PMID- 29377149
TI  - Misfolded proinsulin in the endoplasmic reticulum during development of beta cell
      failure in diabetes.
AB  - The endoplasmic reticulum (ER) is broadly distributed throughout the cytoplasm of
      pancreatic beta cells, and this is where all proinsulin is initially made.
      Healthy beta cells can synthesize 6000 proinsulin molecules per second.
      Ordinarily, nascent proinsulin entering the ER rapidly folds via the formation of
      three evolutionarily conserved disulfide bonds (B7-A7, B19-A20, and A6-A11). A
      modest amount of proinsulin misfolding, including both intramolecular disulfide
      mispairing and intermolecular disulfide-linked protein complexes, is a natural by
      product of proinsulin biosynthesis, as is the case for many proteins. The steady
      state level of misfolded proinsulin-a potential ER stressor-is linked to (1)
      production rate, (2) ER environment, (3) presence or absence of naturally
      occurring (mutational) defects in proinsulin, and (4) clearance of misfolded
      proinsulin molecules. Accumulation of misfolded proinsulin beyond a certain
      threshold begins to interfere with the normal intracellular transport of
      bystander proinsulin, leading to diminished insulin production and hyperglycemia,
      as well as exacerbating ER stress. This is most obvious in mutant INS gene
      induced Diabetes of Youth (MIDY; an autosomal dominant disease) but also likely
      to occur in type 2 diabetes owing to dysregulation in proinsulin synthesis, ER
      folding environment, or clearance.

PMID- 29377153
TI  - Clinical trials for myasthenia gravis: a historical perspective.
AB  - Symposia dedicated to myasthenia gravis and related disorders date back to 1947
      and serve as markers of the progress for the field. We provide a brief historical
      review of therapy development through the lens of the publications that arose
      from the close to quinquennial meetings that have been supported nearly since
      their inception by the Myasthenia Gravis Foundation of America and the New York
      Academy of Sciences. One can appreciate great advances, false starts, and dead
      ends that are found in all fields of medicine. We tally up the score card for MG
      and find points scored, but the win is not yet close.

PMID- 29377152
TI  - A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence
      variant in LAMA5.
AB  - We report a severe defect of neuromuscular transmission in a consanguineous
      patient with a homozygous variant in the laminin alpha5 subunit gene (LAMA5). The
      variant c.8046C > T (p.Arg2659Trp) is rare and has a predicted deleterious
      effect. The affected individual, who also carries a rare homozygous sequence
      variant in LAMA1, had normal cognitive function, but magnetic resonance brain
      imaging showed mild volume loss and periventricular T2 prolongation. Repetitive
      nerve stimulation at 2 Hz showed 50% decrement of compound muscle action
      potential amplitudes but 250% facilitation immediately after exercise, similar to
      that seen in Lambert-Eaton myasthenic syndrome. Endplate studies demonstrated a
      profound reduction of the endplate potential quantal content but normal
      amplitudes of miniature endplate potentials. Electron microscopy showed endplates
      with increased postsynaptic folding that were denuded or only partially occupied
      by small nerve terminals. Expression studies revealed that p.Arg2659Trp caused
      decreased binding of laminin alpha5 to SV2A and impaired laminin-521 cell
      adhesion and cell projection support in primary neuronal cultures. In summary,
      this report describing severe neuromuscular transmission failure in a patient
      with a LAMA5 mutation expands the list of phenotypes associated with defects in
      genes encoding alpha-laminins.

PMID- 29377154
TI  - A novel glycocluster molecule prevents timothy-induced allergic airway
      inflammation in mice.
AB  - BACKGROUND: Allergen-specific immunotherapy (SIT) effectively alleviates type I
      allergic diseases characterized by T helper (Th)2-type immunity. Our recent
      studies have shown that a synthetic trivalent glycocluster, triacedimannose
      (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was
      to compare TADM with two well-known adjuvants, unmethylated cytosine-phosphate
      guanine oligodeoxynucleotide (CpG) and monophosphoryl lipid A (MPLA) in a grass
      allergen-induced chronic allergic inflammation model in mice. METHODS: Female
      BALB/c mice were intranasally sensitized with 50 MUL of timothy grass pollen
      extract (TE) twice a week for a period of 15 weeks. Therapeutic intranasal
      treatments were then performed once a week after the tenth intranasal TE
      instillation using TADM (10 or 25 MUg/50 MUL), CpG-ODN (20 MUg/50 MUL) or MPLA (2
      MUg/50 MUL). Groups of 9-10 animals per treatment were killed 24 hours after the
      last timothy dosage. Blood, bronchoalveolar lavage (BAL) fluids and lung biopsies
      were taken for subsequent analysis. RESULTS: When mice were repeatedly exposed to
      TE for 15 weeks, the number of eosinophils and lymphocytes increased in the BAL
      fluids. The eosinophil and lymphocyte counts decreased dose-dependently and were
      practically abolished in the mice treated with TADM. Treatments with MPLA or CpG
      significantly increased the numbers of neutrophils, while CpG nonsignificantly
      decreased eosinophilia compared to timothy exposure. CONCLUSIONS: A novel
      synthetic glycocluster molecule inhibited the development of grass-induced
      eosinophilic pulmonary inflammation in mice when administrated in the airways.
      This compound could be a candidate to be used either as an adjuvant in SIT or as
      a topical anti-inflammatory treatment.

PMID- 29377155
TI  - A novel HD-ZIP IV/MIXTA complex promotes glandular trichome initiation and
      cuticle development in Artemisia annua.
AB  - Glandular trichomes and cuticles are both specialized structures that cover the
      epidermis of aerial plant organs. The former are commonly regarded as
      'biofactories' for producing valuable natural products. The latter are generally
      considered as natural barriers for defending plants against abiotic and biotic
      stresses. However, the regulatory network for their formation and relationship
      remains largely elusive. Here we identify a homeodomain-leucine zipper (HD-ZIP)
      IV transcription factor, AaHD8, directly promoting the expression of AaHD1 for
      glandular trichome initiation in Artemisia annua. We found that AaHD8 positively
      regulated leaf cuticle development in A. annua via controlling the expression of
      cuticle-related enzyme genes. Furthermore, AaHD8 interacted with a MIXTA-like
      protein AaMIXTA1, a positive regulator of trichome initiation and cuticle
      development, forming a regulatory complex and leading to enhanced transcriptional
      activity in regulating the expression of AaHD1 and cuticle development genes. Our
      results reveal a molecular mechanism by which a novel HD-ZIP IV/MIXTA complex
      plays a significant role in regulating epidermal development, including glandular
      trichome initiation and cuticle formation.

PMID- 29377156
TI  - Guided undersampling classification for automated radiation therapy quality
      assurance of prostate cancer treatment.
AB  - PURPOSE: To test the use of well-studied and widely used classification methods
      alongside newly developed data-filtering techniques specifically designed for
      imbalanced-data classification in order to demonstrate proof of principle for an
      automated radiation therapy (RT) quality assurance process on prostate cancer
      treatment. METHODS: A series of acceptable (majority class, n = 61) and erroneous
      (minority class, n = 12) RT plans as well as a disjoint set of acceptable plans
      used to develop features (n = 273) were used to develop a dataset for testing. A
      series of five widely used imbalanced-data classification algorithms were tested
      with a modularized guided undersampling procedure that includes ensemble-outlier
      filtering and normalized-cut sampling. RESULTS: Hybrid methods including either
      ensemble-outlier filtering or both filtering and normalized-cut sampling yielded
      the strongest performance in identifying unacceptable treatment plans.
      Specifically, five methods demonstrated superior performance in both area under
      the receiver operating characteristics curve and false positive rate when the
      true positive rate is equal to one. Furthermore, ensemble-outlier filtering
      significantly improved results in all but one hybrid method (p < 0.01). Finally,
      ensemble-outlier filtering methods identified four minority instances that were
      considered outliers in over 96% of cross-validation iterations. Such instances
      may be considered distinct planning errors and merit additional inspection,
      providing potential areas of improvement for the planning process. CONCLUSIONS:
      Traditional imbalanced-data classification methods combined with ensemble-outlier
      filtering and normalized-cut sampling provide a powerful framework for
      identifying erroneous RT treatment plans. The proposed methodology yielded strong
      classification performance and identified problematic instances with high
      accuracy.

PMID- 29377157
TI  - Role of the carotid body chemoreceptors in glucose homeostasis and
      thermoregulation in humans.
AB  - The carotid bodies (CBs) are multi-modal sensory organs located bilaterally at
      the bifurcation of the carotid artery and innervated by the carotid sinus nerve
      (Hering's nerve), a branch of the IX cranial nerve. While the CBs (or
      embryologically analogous structures) are well known as the dominant oxygen
      sensing organ in vertebrates, in mammals there is evidence that the CBs may also
      sense glucose and temperature, and respond to circulating hormones and other
      factors. Additionally, the CBs likely participate in regulating baseline levels
      of sympathetic tone. In this brief review, we focus on the evolution of our
      efforts to understand 'what else' beyond oxygen sensing the CBs do in humans.

PMID- 29377158
TI  - Comparative effectiveness clinical trials to advance treatment of myasthenia
      gravis.
AB  - Myasthenia gravis (MG) presents many challenges for establishing treatment
      efficacy through clinical trials. Among these are the rarity and heterogeneity of
      the disease, spontaneous fluctuations, prolonged latency to effect for many
      immunosuppressive drugs, and the uncertain generalizability of results from
      randomized controlled trials (RCTs). Prospective observational study designs may
      overcome some of these limitations, but attention is required to ensure that
      internal validity is not compromised. Observational comparative effectiveness
      research (CER) utilizes data obtained during routine clinical care to evaluate
      the effectiveness of interventions in real-life practice conditions, thereby
      improving generalizability to the clinic. Compared with RCTs, observational CER
      studies may be less resource intensive and costly. Recent advances that have
      improved the feasibility of CER studies for MG are (1) the development of MG
      common data elements, (2) the publication of international consensus guidance for
      MG treatment, and (3) the development of a web-based REDCap database that can be
      shared and adapted to standardize data collection. This infrastructure could be
      used for multisite comparisons of commonly used therapies and provides
      longitudinal information on patient- and clinician-centered MG outcome measures.
      A challenge is to design studies that address the potential limitations of
      observational trials, such as confounding and selection and information bias.

PMID- 29377159
TI  - "Think Like a Man": How Sexual Cultural Scripting and Masculinity Influence
      Changes in Men's Use of Intimate Partner Violence.
AB  - The purpose of the study was to (a) explore the relationship between sexual
      cultural scripting and traditional masculine norms on changes in intimate partner
      violence (IPV) perpetration, and (b) examine traditional masculine norms as an
      effect modifier among young heterosexual men. This study is a secondary data
      analysis of a prospective cohort study of 119 young heterosexual men who were
      followed for 6 months. The adjusted logistic regression results revealed that
      sexual cultural scripting norms were associated with an increased odds of
      emotional IPV perpetration and traditional masculine norms were associated with
      an increased odds of physical IPV perpetration in the past 6 months. There were
      no significant interaction effects between sexual cultural scripting and
      traditional masculine norms on IPV perpetration. These findings suggest that
      socially constructed norms and beliefs surrounding masculinity, femininity, and
      how women and men interact in sexual relationships are important constructs for
      understanding the etiology of young men's use of violence against a female
      partner. While primary IPV interventions targeting young men do address
      masculinity, sexual cultural scripting is an additional concept that should also
      be addressed.

PMID- 29377161
TI  - Phylogeny and species delineation in the marine diatom Pseudo-nitzschia
      (Bacillariophyta) using cox1, LSU, and ITS2 rRNA genes: A perspective in
      character evolution.
AB  - Analyses of the mitochondrial cox1, the nuclear-encoded large subunit (LSU), and
      the internal transcribed spacer 2 (ITS2) RNA coding region of Pseudo-nitzschia
      revealed that the P. pseudodelicatissima complex can be phylogenetically grouped
      into three distinct clades (Groups I-III), while the P. delicatissima complex
      forms another distinct clade (Group IV) in both the LSU and ITS2 phylogenetic
      trees. It was elucidated that comprehensive taxon sampling (sampling of
      sequences), selection of appropriate target genes and outgroup, and alignment
      strategies influenced the phylogenetic accuracy. Based on the genetic divergence,
      ITS2 resulted in the most resolved trees, followed by cox1 and LSU. The
      morphological characters available for Pseudo-nitzschia, although limited in
      number, were overall in agreement with the phylogenies when mapped onto the ITS2
      tree. Information on the presence/absence of a central nodule, number of rows of
      poroids in each stria, and of sectors dividing the poroids mapped onto the ITS2
      tree revealed the evolution of the recently diverged species. The morphologically
      based species complexes showed evolutionary relevance in agreement with molecular
      phylogeny inferred from ITS2 sequence-structure data. The data set of the
      hypervariable region of ITS2 improved the phylogenetic inference compared to the
      cox1 and LSU data sets. The taxonomic status of P. cuspidata and P.
      pseudodelicatissima requires further elucidation.

PMID- 29377160
TI  - IgG4-mediated autoimmune diseases: a niche of antibody-mediated disorders.
AB  - Immunoglobulin 4 (IgG4) is one of four human IgG subclasses and has several
      unique functional characteristics. It exhibits low affinity for complement and
      for most Fc receptors. It furthermore has generally high affinity for its
      antigen, with binding occurring in a monovalent fashion, as IgG4 can exchange Fab
      arms with other IgG4 molecules. Because of these characteristics, IgG4 is
      believed to block its targets and prevent inflammation, which, depending on the
      setting, can have a protective or pathogenic effect. One example of IgG4
      pathogenicity is muscle-specific kinase (MuSK) myasthenia gravis (MG), in which
      patients develop IgG4 MuSK autoantibodies, resulting in muscle weakness. As a
      consequence of the distinct IgG4 characteristics, the pathomechanism of MuSK MG
      is very different from IgG1-and IgG3-mediated autoimmune diseases, such as
      acetylcholine receptor MG. In recent years, new autoantibodies in a spectrum of
      autoimmune diseases have been discovered. Interestingly, some were found to be
      predominantly IgG4. These IgG4-mediated autoimmune diseases share many
      pathomechanistic aspects with MuSK MG, suggesting that IgG4-mediated autoimmunity
      forms a separate niche among the antibody-mediated disorders. In this review, we
      summarize the group of IgG4-mediated autoimmune diseases, discuss the role of
      IgG4 in MuSK MG, and highlight interesting future research questions for IgG4
      mediated autoimmunity.

PMID- 29377162
TI  - Serological and experimental studies in different forms of myasthenia gravis.
AB  - Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40
      years and have been important in the diagnosis of myasthenia gravis (MG), and its
      recognition in patients of different ages and thymic pathologies. The 10-20% of
      patients who do not have AChR antibodies are now known to comprise different
      subgroups, the most commonly reported of which is patients with antibodies to
      muscle-specific kinase (MuSK). The use of cell-based assays has extended the
      repertoire of antibody tests to clustered AChRs, low-density lipoprotein receptor
      related protein 4, and agrin. Autoantibodies against intracellular targets,
      namely cortactin, titin, and ryanodine receptor (the latter two being associated
      with the presence of thymoma), may also be helpful as biomarkers in some
      patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1,
      IgG2, and IgG3 antibodies, collectively, have effects that question the dominance
      of IgG4 as the sole pathologic factor in MuSK MG. After a brief historical
      review, we define the different subgroups and summarize the antibody
      characteristics. Experiments to demonstrate the in vitro and in vivo pathogenic
      roles of MuSK antibodies are discussed.

PMID- 29377163
TI  - Sulfur amino acid restriction-induced changes in redox-sensitive proteins are
      associated with slow protein synthesis rates.
AB  - The mechanisms underlying life span extension by sulfur amino acid restriction
      (SAAR) are unclear. Cysteine and methionine are essential for the biosynthesis of
      proteins and glutathione (GSH), a major redox buffer in the endoplasmic reticulum
      (ER). We hypothesized that SAAR alters protein synthesis by modulating the redox
      milieu. Male F344-rats were fed control (CD: 0.86% methionine without cysteine)
      and SAAR diets (0.17% methionine without cysteine) for 12 weeks. Growth rates,
      food intake, cysteine and GSH levels, proteins associated with redox status and
      translation, and fractional protein synthesis rates (FSRs) were determined in
      liver. Despite a 40% higher food intake, growth rates for SAAR rats were 27% of
      those fed CD. Hepatic free cysteine in SAAR rats was 55% compared with CD rats.
      SAAR altered tissue distribution of GSH, as hepatic and erythrocytic levels were
      56% and 196% of those in CD rats. Lower GSH levels did not induce ER stress
      (i.e., unchanged expression of Xbp1s , Chop, and Grp78), but activated PERK and
      its substrates eIF2-alpha and NRF2. SAAR-induced changes in translation
      initiation machinery (higher p-eIF2-alpha and 4E-BP1, and lower eIF4G-1) resulted
      in slower protein synthesis rates (53% of CD). Proteins involved in the
      antioxidant response (NRF2, KEAP1, GCLM, and NQO1) and protein folding (PDI and
      ERO1-alpha) were increased in SAAR. Lower FSR and efficient protein folding might
      be improving proteostasis in SAAR.

PMID- 29377164
TI  - Therapeutic applications of betulinic acid nanoformulations.
AB  - Betulinic acid (BA), a naturally occurring plant-derived pentacyclic
      triterpenoid, has gained attention in recent years owing to its broad-spectrum
      biological and medicinal properties. Despite the pharmacological activity of BA,
      it has been associated with some drawbacks, such as poor aqueous solubility and
      short half-life in vivo, which limit therapeutic application. To solve these
      problems, much work in recent years has focused on enhancing BA's aqueous
      solubility, half-life, and efficacy by using nanoscale drug delivery systems.
      Several different kinds of nanoscale delivery systems-including polymeric
      nanoparticles, magnetic nanoparticles, liposomes, polymeric conjugates,
      nanoemulsions, cyclodextrin complexes, and carbon nanotubes-have been developed
      for the delivery of BA. Here, we focus on the recent developments of novel
      nanoformulations used to deliver BA in order to improve its efficacy.

PMID- 29377165
TI  - Pathophysiological mechanisms of autoimmunity.
AB  - Autoimmune diseases (AIDs) are chronic disorders characterized by inflammatory
      reactions against self-antigens that can be either systemic or organ specific.
      AIDs can differ in their epidemiologic features and clinical presentations, yet
      all share a remarkable complexity. AIDs result from an interplay of genetic and
      epigenetic factors with environmental components that are associated with
      imbalances in the immune system. Many of the pathogenic mechanisms of AIDs are
      also implicated in myasthenia gravis (MG), an AID in which inflammation of the
      thymus leads to a neuromuscular disorder. Our goal here is to highlight the
      similarities and differences between MG and other AIDs by reviewing the common
      transcriptome signatures and the development of germinal centers and by
      discussing some unresolved questions about autoimmune mechanisms. This review
      will propose hypotheses to explain the origin of regulatory T (Treg ) cell
      defects and the causes of chronicity and specificity of AIDs.

PMID- 29377166
TI  - Challenging the current model of early-onset myasthenia gravis pathogenesis in
      the light of the MGTX trial and histological heterogeneity of thymectomy
      specimens.
AB  - The MGTX trial provided evidence that, in general, thymectomy is beneficial in
      adult patients up to 60 years of age with anti-acetylcholine receptor-positive,
      nonthymomatous myasthenia gravis (MG). This finding supports the long-held view
      that the pathogenesis of this type of MG (early-onset MG (EOMG)) starts inside
      the thymus, results in the long-term intrathymic recruitment of autoantibody
      producing B cells and plasma cells, and eventually spreads to the peripheral
      immune system. However, observed clinical responses to treatment in the MGTX
      trial were diverse. This might be due to heterogeneous epidemiological and
      genetic features of EOMG patients and variable durations of corticosteroid
      treatment before surgery, including a paucity of patients that were
      corticosteroid naive. Furthermore, the observed histological heterogeneity
      suggests that a single pathogenetic model may not fully reflect the spectrum of
      events that modify the course of EOMG. Here, we describe the morphology of the
      normal and MG-associated thymus, how to evaluate morphological changes, and the
      current pathogenetic model of EOMG and discuss how it could be refined by
      integrating MGTX-derived histological findings in thymectomy specimens and
      associated clinical observations.

PMID- 29377167
TI  - Acetylcholine receptor-specific immunosuppressive therapy of experimental
      autoimmune myasthenia gravis and myasthenia gravis.
AB  - Experimental autoimmune myasthenia gravis (EAMG) and myasthenia gravis (MG) are
      caused by autoantibodies to the extracellular domain of muscle nicotinic
      acetylcholine receptors (AChRs). Autoantibodies to the cytoplasmic domain of
      AChRs do not cause EAMG because they cannot bind AChRs in vivo. The ideal MG
      therapy would quickly and permanently suppress only the pathological autoimmune
      response to AChRs. We have developed a specific immunosuppressive therapy for
      EAMG that involves immunizing rats with bacterially expressed cytoplasmic domains
      of human muscle AChRs. Therapy prevents onset of chronic EAMG, rapidly suppresses
      ongoing EAMG, and is potent, robust, long lasting, and safe, because the
      therapeutic antigen cannot induce EAMG. The therapy was developed using
      incomplete Freund's adjuvant, but is likely to work equally well with alum
      adjuvants routinely used for human immunizations. Therapeutic mechanisms may
      involve a combination of antibody-mediated feedback suppression and regulatory T
      and/or B lymphocytes.

PMID- 29377168
TI  - Technical Note: Feasibility study of titanium markers in choroidal melanoma
      localization for proton beam radiation therapy.
AB  - PURPOSE: The purpose of this study is to explore the feasibility of the use of
      titanium fiducial markers to minimize the metallic artifact seen with tantalum
      markers which causes significant distortion on postoperative orbital CT scans.
      METHOD: We designed and constructed the titanium markers in the shop of Crocker
      Nuclear Laboratory, UC Davis, CA. The markers were placed on an eyeball phantom.
      The eyeball was inserted into the Rando phantom in the orbital space. The Rando
      phantom was imaged with coplanar x rays on Nucletron simulator at UCSF, on
      digital panel on the eye beam line at CNL eye treatment facility and on CT
      scanner at UCSF. RESULTS: The titanium markers can be clearly seen on the hard
      copy of x rays and on digital panel. The CT scan of an orbit using tantalum
      markers on the right eye and titanium markers on the left eye shows the metal
      artifact from tantalum markers. Titanium markers show very little distortion on
      CT images. CONCLUSION: The present study describes these markers and their
      relative benefit in comparison with tantalum marker, which has been used for
      localizing ocular tumor for decades.

PMID- 29377169
TI  - Interactive effects of LPS and dentine matrix proteins on human dental pulp stem
      cells.
AB  - AIM: To investigate the combinatorial effects of lipopolysaccharide (LPS) and
      extracted dentine matrix proteins (eDMP) on regenerative and inflammatory
      responses in human dental pulp stem cells (DPSCs). METHODOLOGY: Culture media
      were supplemented with several concentrations of LPS, eDMP and combinations of
      both. Cell viability was assessed over 1 week by MTT assay; cell survival was
      evaluated after 24 h and 7 days by flow cytometry. The expression of
      mineralization-associated marker genes was determined by real-time quantitative
      polymerase chain reaction (RT-qPCR). To analyse the inflammatory response,
      secretion of interleukin 6 (IL-6) was quantified in the initial and the late
      phase of cell culture by enzyme-linked immunosorbent assay (ELISA). Data were
      treated nonparametrically and Mann-Whitney U-tests were performed to compare all
      experimental groups (alpha = 0.05). RESULTS: Whereas LPS had no impact on
      viability, eDMP led to a concentration-dependent decrease, which was significant
      after 7 days (P <= 0.024). A moderate decline of cell survival induced by LPS was
      detected after 48 h (P <= 0.026), whereas eDMP was able to reverse this effect.
      eDMP alone caused increased expression of tested marker genes, LPS had no
      regulatory effect. Combined eDMP and LPS induced an upregulation of collagen type
      I and osteocalcin, whereas expression levels of dentine matrix acidic
      phosphoprotein and dentine sialophosphoprotein were similar to the control. IL-6
      secretion was increased by LPS over time. eDMP markedly elevated initial
      production of IL-6 (P <= 0.002), but suppressed LPS-induced cytokine production
      in the later phase. CONCLUSIONS: Lipopolysaccharide did not affect cell viability
      but interfered with odontoblast-like cell differentiation of DPSCs. Proteins from
      the dentine matrix may have a protective effect, attenuate the detrimental impact
      of LPS and thus play an important role during pulp repair.

PMID- 29377170
TI  - Effect of root canal irrigation protocols on the dislocation resistance of
      mineral trioxide aggregate-based materials: A systematic review of laboratory
      studies.
AB  - The aim of this systematic review was to address the question: Do different
      irrigating protocols have an impact on the dislocation resistance of mineral
      trioxide aggregate (MTA)-based materials? The review was performed using a well
      defined search strategy in three databases (PubMed, Scopus, Web of Science) to
      include laboratory studies performed between January 1995 and May 2017, in
      accordance with PRISMA guidelines. Two reviewers analysed the papers, assessed
      the risk of bias and extracted data on teeth used, sample size, size of root
      canal preparation, type of MTA-based material, irrigants, canal filling method,
      storage method and duration, region of roots and the parameters of push-out
      testing (slice thickness, plunger dimensions and plunger loading direction), the
      main results and dislocation resistance values (in MPa). From 255 studies, 27
      were included for full-text analysis. Eight papers that met the inclusion
      criteria were included in this review. There was a wide variation in dislocation
      resistance due to differences in irrigation sequence, time and concentration of
      irrigants, storage method and duration, and the parameters of push-out bond
      strength testing. A meta-analysis was not done but qualitative synthesis of the
      included studies was performed. No definitive conclusion could be drawn to
      evaluate the effect of irrigation protocols on dislocation resistance of MTA
      based materials. Recommendations have been provided for standardized testing
      methods and reporting of future studies, so as to obtain clinically relevant
      information and to understand the effects of irrigating protocols on root canal
      sealers and their interactions with the dentine walls of root canals.

PMID- 29377171
TI  - The effect of adjusting the pH of local anaesthetics in dentistry: a systematic
      review and meta-analysis.
AB  - The acidic nature of commercial local anaesthetics (LAs) can cause pain during
      infiltration and delay the onset of anaesthesia. It is suggested that adjusting
      the pH of anaesthetic agents could minimize these effects. This systematic review
      aimed to evaluate the efficacy of buffered LAs in reducing infiltration pain and
      onset time during dental procedures. MEDLINE, Embase, Scopus and Scielo databases
      were searched up to April 2017. Randomized controlled trials comparing buffered
      and unbuffered LAs for intraoral injections were included. Risk of bias was
      assessed using the Cochrane Collaboration tool. Data upon injection pain and
      onset time were pooled in a random-effects model. Subgroup analyses compared
      normal and inflamed tissues, and terminal infiltrations and inferior alveolar
      nerve (IAN) blocks. Meta-regressions were performed to explain heterogeneity.
      Fourteen articles were included in this review. Lidocaine with epinephrine was
      the most used anaesthetic combination. Nonlidocaine studies (n = 2) were not
      pooled in the meta-analysis. Buffered lidocaine did not result in less pain
      during intraoral injections: mean difference -6.4 (95% CI -12.81 to 0.01) units
      in a 0-100 scale. Alkalinized lidocaine did not reduce the onset time in normal
      tissues when terminal infiltration techniques were used, but resulted in a more
      rapid onset for IAN blocks (-1.26 min) and in inflamed tissues (-1.37 min);
      however, this change may not be clinically relevant, considering the time
      required to prepare the buffered agent. Studies performed using other anaesthetic
      salts did not show robust and clinically significant results in favour of
      alkalinization.

PMID- 29377172
TI  - High-risk inferior myocardial infarction: Can speckle tracking predict proximal
      right coronary lesions?
AB  - BACKGROUND: It is important to diagnose right ventricular (RV) infarction in the
      setting of acute inferior myocardial infarction (MI). We aimed to improve the
      diagnostic accuracy of RV infarction and identify a high-risk subset of inferior
      MI patients with proximal RCA lesions. HYPOTHESIS: We tried to find the link
      between speckle tracking and coronaries in high risk inferior infarction METHODS:
      This study included 68 patients within 24 hours of first acute inferior MI. Group
      1 (n = 49) isolated inferior MI; group 2 (n = 19) inferior and RV MI.
      echocardiography for RV free wall longitudinal strain (FWLS), RV fractional area
      change (FAC), tricuspid annular plane systolic excursion (TAPSE), RV myocardial
      performance index (MPI) and peak systolic velocity (S'). RESULTS: Group 2 had
      higher MPI by tissue Doppler and 2D-RV average FWLS, whereas RV FAC, S', and
      TAPSE were lower (P < 0.001). In group 1, 14.4% had a significant proximal RCA
      lesion with impaired RV function. RV average FWLS at a cutoff value >= - 19.7%
      can predict proximal RCA culprit lesion with 91.7% sensitivity and 70.5%
      specificity, which was detected as an independent predictor in multivariate
      logistic regression (odds ratio: 37.75, P = 0.036). CONCLUSIONS: 2D RV average
      FWLS at a cutoff of >= - 19.7% is a useful added tool for diagnosis of RV
      involvement and an independent predictor to rule in proximal RCA culprit lesion
      in inferior-wall MI patients in the emergency department.

PMID- 29377174
TI  - Muddy puddles - the microbiology of puddles located outside tertiary university
      teaching hospitals.
AB  - : In the British Isles, the frequency of rain results in the formation of puddles
      on footpaths and roads in/around hospitals. No data are available demonstrating
      the microbiological composition of such puddles and therefore a study was
      undertaken to examine the microbiology of puddles in the grounds of two tertiary
      university-teaching hospitals (18 sites) and compared with control puddles from
      non-hospital rural environments (eight sites), estimating (i) total viable count;
      (ii) identification of organisms in puddles; (iii) enumeration of Escherichia
      coli: (iv) detection of Extended Spectrum beta-Lactamase producing organisms and
      (v) direct antimicrobial susceptibility testing. A mean count of 2.3 * 103  CFU
      per ml and 1.0 * 109  CFU per ml was obtained for hospital and non-hospital
      puddles respectively. Isolates (n = 77; 54 hospital and 23 non-hospital) were
      isolated comprising of 23 species among 17 genera (hospital sites), where the
      majority (10/16; 62.5%) of genera identified were Gram-negative approximately, a
      fifth (20.6%) were shared by hospital and non-hospital rural samples. Escherichia
      coli was detected in half of the hospital puddles and under-half (37.5%) of the
      rural puddles extended spectrum beta-lactamase organisms were not detected in any
      samples examined. Rainwater puddles from the hospital and non-hospital
      environments contain a diverse range of bacteria, which are capable of causing
      infections. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the
      presence of a wide diversity of bacterial taxa associated with rainwater puddles
      around hospitals, many of which are capable of causing human disease. Of clinical
      significance is the presence of Pseudomonas aeruginosa isolated from a hospital
      puddle, particularly for patients with cystic fibrosis. The presence of
      potentially disease-causing bacteria in puddles in and around hospitals
      identifies a new potential environmental reservoir of bacteria. Furthermore work
      is now needed to define their potential of entering or exiting hospital wards by
      contaminated footwear.

PMID- 29377173
TI  - Prospective evaluation of antibody response to Streptococcus gallolyticus and
      risk of colorectal cancer.
AB  - The gut microbiome is increasingly implicated in colorectal cancer (CRC)
      development. A subgroup of patients diagnosed with CRC show high antibody
      responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However,
      it is unclear whether the association is also present pre-diagnostically. We
      assessed the association of antibody responses to SGG proteins in pre-diagnostic
      serum samples with CRC risk in a case-control study nested within a prospective
      cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time
      between blood draw and diagnosis 3.4 years) and 485 matched controls in the
      European Prospective Investigation into Nutrition and Cancer (EPIC) study were
      analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds
      ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable
      conditional logistic regression models. Antibody positivity for any of the 11 SGG
      proteins was significantly associated with CRC risk with 56% positive controls
      compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two
      or more proteins of a previously identified SGG 6-marker panel with greater CRC
      specificity was also observed among 9% of controls compared to 17% of CRC cases,
      corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44
      3.27). In this prospective nested case-control study, we observed a positive
      association between antibody responses to SGG and CRC development in serum
      samples taken before evident disease onset. Further work is required to establish
      the possibly etiological significance of these observations and whether SGG
      serology may be applicable for CRC risk stratification.

PMID- 29377175
TI  - The effect of maternal exposure to di-(2-ethylhexyl)-phthalate on fetal cardiac
      development in mice.
AB  - Accumulating evidence has suggested a link between maternal di-(2-ethylhexyl)
      phthalate (DEHP) exposure and various developmental abnormalities. However, the
      evidence regarding the effect of maternal DEHP exposure on fetal cardiac
      development is scarce. The present study aimed to determine the effect of
      maternal DEHP exposure on fetal cardiac development in mice and explore the
      possible involved mechanism preliminarily. The C57BL mice were randomly divided
      into four groups: the vehicle group (corn oil, n = 10), 250 mg kg-1 DEHP group (n
      = 15), 500 mg kg-1 DEHP group (n = 20) and 1 g kg-1 DEHP group (n = 20). Pregnant
      dams in different group received respective intervention by gavage once daily
      from embryonic day (E)6.5 to E14.5. Maternal weights were monitored every day and
      samples were collected at E15.5. Hematoxylin and eosin staining was used to
      examine fetal cardiac malformations. Real-time quantitative polymerase chain
      reaction and western blot were applied to detect peroxisome proliferator
      activated receptor (PPAR)alpha/PPARgamma/Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and
      protein expression, respectively. Maternal DEHP exposure significantly decreased
      maternal body weight, fetal weight and placental weight, and remarkably elevated
      fetal cardiac malformations rate. The phenotypes of cardiac anomalies mainly
      include septal defects, ventricular myocardium noncompaction and cardiac
      hypoplasia. Higher doses DEHP (500 mg kg-1 and 1 g kg-1 ) could significantly
      decreased fetal cardiac Gata4/Mef2c/Chf1 expression, while PPARgamma expression
      was upregulated. Maternal exposure to higher doses of DEHP could result in fetal
      cardiac development malformations in mice and it might have resulted from the
      inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARgamma activation.

PMID- 29377176
TI  - Agrin and LRP4 antibodies as new biomarkers of myasthenia gravis.
AB  - Myasthenia gravis (MG) is a common disorder that affects the neuromuscular
      junction. It is caused by antibodies against acetylcholine receptor and muscle
      specific tyrosine kinase; however, some MG patients do not have antibodies
      against either of the proteins. Recent studies have revealed antibodies against
      agrin and its receptor LRP4-both critical for neuromuscular junction formation
      and maintenance-in MG patients from various populations. Results from
      experimental autoimmune MG animal models indicate that anti-LRP4 antibodies are
      causal to MG. Clinical studies have begun to reveal the significance of the new
      biomarkers. With their identification, MG appears to be a complex disease entity
      that can be classified into different subtypes with different etiology, each with
      unique symptoms. Future systematic studies of large cohorts of well-diagnosed MG
      patients are needed to determine whether each subtype of patients would respond
      to different therapeutic strategies. Results should contribute to the goal of
      precision medicine for MG patients. Anti-agrin and anti-LRP4 antibodies are also
      detectable in some patients with amyotrophic lateral sclerosis or Lou Gehrig's
      disease; however, whether they are a cause or response to the disorder remains
      unclear.

PMID- 29377178
TI  - Distinct patterns of gene expression in human cardiac fibroblasts exposed to
      rapamycin treatment or methionine restriction.
AB  - Both methionine restriction and rapamycin treatment are robust longevity
      enhancing regimens for which the mechanisms remain unclear. Cellular senescence
      is a major contributor to the aging process, and we find that both the methionine
      and rapamycin regimens delay or prevent activation of the senescence program in
      human cells. Using a transcriptome-wide analysis, we examined the impact of
      methionine restriction and rapamycin treatment on senescence-associated gene
      expression in human cardiac fibroblasts. Our findings have been integrated into
      gene expression data sets from human lung and skin fibroblasts during senescence.
      The data demonstrate both common and tissue-specific aspects to the senescent
      phenotype in these cell types. For example, cardiac fibroblasts express brain
      naturetic peptide, a clinically relevant marker for cardiac failure, whereas
      senescent cells from all three tissues express at least one of the insulin-like
      growth factor (IGF)-binding proteins. The IGF-binding proteins are tissue
      specific mediators of IGF-1, a growth factor required for proliferation of all
      tissues. These data suggest that senescent cells serve tissue-specific roles.
      Moreover, the prolongevity regimens produce distinct patterns of gene expression.

PMID- 29377177
TI  - EAACI Position paper on the standardization of nasal allergen challenges.
AB  - Nasal allergen challenge (NAC) is an important tool to diagnose allergic
      rhinitis. In daily clinical routine, experimentally, or when measuring
      therapeutic success clinically, nasal allergen challenge is fundamental. It is
      further one of the key diagnostic tools when initiating specific allergen
      immunotherapy. So far, national recommendations offered guidance on its
      execution; however, international divergence left many questions unanswered.
      These differences in the literature caused EAACI to initiate a task force to
      answer unmet needs and find a consensus in executing nasal allergen challenge. On
      the basis of a systematic review containing nasal allergen challenges of the past
      years, task force members reviewed evidence, discussed open issues, and studied
      variations of several subjective and objective assessment parameters to propose a
      standardized way of a nasal allergen challenge procedure in clinical practice.
      Besides an update on indications, contraindications, and preparations for the
      test procedure, main recommendations are a bilaterally challenge with
      standardized allergens, with a spray device offering 0.1 mL per nostril. A
      systematic catalogue for positivity criteria is given for the variety of
      established subjective and objective assessment methods as well as a schedule for
      the challenge procedure. The task force recommends a unified protocol for NAC for
      daily clinical practice, aiming at eliminating the previous difficulty of
      comparing NAC results due to unmet needs.

PMID- 29377179
TI  - Targeting EGFRL858R/T790M and EGFRL858R/T790M/C797S resistance mutations in
      NSCLC: Current developments in medicinal chemistry.
AB  - Both the first-generation reversible epidermal growth factor receptor (EGFR)
      inhibitors gefitinib and erlotinib and the second-generation covalent epidermal
      growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) afatinib have
      significantly improved the survival of non-small-cell lung cancer (NSCLC)
      patients with activating EGFR mutations. However, a secondary EGFRT790M mutation
      leads to the clinically acquired resistance to the first- and second-generation
      EGFR-TKIs drugs. A number of the third-generation wild-type sparing EGFR
      inhibitors, for example, WZ4002, CO1686, AZD9291, HM61713, EGF816, ASP8173, and
      PF0674775, have been developed, among which AZD9291 has been approved by US FDA
      for the treatment of NSCLC patients with EGFRT790M . More recently, a tertiary
      EGFRC797S mutation was reported as the dominant resistance mechanism to the third
      generation irreversible inhibitors. It is highly desirable to develop the fourth
      generation EGFR inhibitors. This review summarizes the mechanisms of acquired
      resistance and the latest medicinal chemistry advances on the third- and fourth
      generation EGFR inhibitors, with special attention being paid to the allosteric
      and reversible inhibitors combating the tertiary EGFRC797S mutation.

PMID- 29377180
TI  - Tissue influx of neutrophils and monocytes is delayed during development of
      trovafloxacin-induced tumor necrosis factor-dependent liver injury in mice.
AB  - Idiosyncratic drug-induced liver injury (iDILI) has a poorly understood
      pathogenesis. However, iDILI is often associated with inflammatory stress signals
      in human patients as well as animal models. Tumor necrosis factor (TNF) and
      neutrophils play a key role in onset of trovafloxacin (TVX)-induced iDILI, but
      the exact role of neutrophils and other leukocytes remains to be defined. We
      therefore set out to study the kinetics of immunological changes during the
      development of TVX-induced iDILI in the established murine model of acute liver
      injury induced by administration of TVX and TNF. Initially, TNF stimulated the
      appearance of leukocytes, in particular neutrophils, into the liver of TVX
      treated mice, but even more so in control mice treated with the non-DILI inducing
      analogue levofloxacin (LVX) or saline as vehicle (Veh). This difference was
      apparent at 2 hours after TNF administration, but at 4 hours, the relative
      neutrophil amounts were reduced again in Veh- and LVX-treated mice whereas the
      amounts in TVX-treated mice remained at the same increased level as at 2 hours.
      The influx of monocytes/macrophages, which was unaffected in Veh- and LVX-treated
      mice was markedly reduced or even absent in TVX-treated mice. Unlike controls,
      mice receiving TVX + TNF display severe hepatotoxicity with clear pathology and
      apoptosis, coagulated hepatic vessels and increased alanine aminotransferase
      levels and interleukin 6/10 ratios. Findings indicate that TVX delays the acute
      influx of neutrophils and monocytes/macrophages. Considering their known anti
      inflammatory functions, the disruption of influx of these innate immune cells may
      hamper the resolution of initial cytotoxic effects of TVX and thus contribute to
      liver injury development.

PMID- 29377181
TI  - Efficacy of Glucose or Amino Acid-Based Commercial Beverages in Meeting Oral
      Rehydration Therapy Goals After Acute Hypertonic and Isotonic Dehydration.
AB  - BACKGROUND: The efficacy of different commercial beverage compositions for
      meeting oral rehydration therapy (ORT) goals in the treatment of acute
      dehydration in healthy humans has not been systematically tested. The objective
      of the study was to compare fluid retention, plasma volume (PV), and interstitial
      fluid (ISF) volume restoration when using 1 popular glucose-based and 1 novel
      amino acid-based (AA) commercial ORT beverage following experimental hypertonic
      or isotonic dehydration. METHODS: Twenty-six healthy adults (21 males, 5 females)
      underwent either a controlled bout of hypertonic (n = 13) or isotonic (n = 13)
      dehydration (3%-4% body mass) via eccrine or renal body water and electrolyte
      losses induced using exercise-heat stress (EHS) or Lasix administration (LAS),
      respectively. Rehydration was achieved over 90 minutes by matching fluid intake
      to water losses (1:1) using a sports drink (SP) or AA commercial ORT beverage.
      Fluid retention (water and electrolytes), PV, and ISF volume changes were tracked
      for 180 minutes. RESULTS: AA produced significantly (P <0.05) greater fluid
      retention (75% vs 57%), ISF volume restoration, and tended (P = 0.06) to produce
      greater PV restoration in trial EHS. In trial LAS, neither beverage exceeded 65%
      retention, but AA replaced electrolytes and preserved ISF volume better than SP
      (P <0.05). CONCLUSION: The results of this study demonstrate superior rehydration
      when using AA compared with SP for both hypertonic and isotonic dehydration.

PMID- 29377182
TI  - Dobrava hantavirus variants found in Apodemus flavicollis mice in Kirklareli
      Province, Turkey.
AB  - Hantaviruses infect humans via inhalation of viral particles within secretions of
      infected rodents or rarely through direct contact with infected rodents.
      Determining the prevalence of hantavirus infections among rodent populations is
      of vital importance to obtain information on hantavirus-related cases and to
      predict possible outbreaks. We hypothesized that DOBV strains circulating in the
      Thrace Region in Turkey would be related to other Balkan DOBV strains. In this
      study, hantavirus infections in the rodent population of the Kirklareli-Igneada
      Region (north-western Turkey, near the Bulgarian border) were investigated. This
      region is of particular importance, as it is located in the south-eastern margin
      of the European continent and was used as an entrance point of Asian faunal
      elements into Europe. DOBV infection was detected in eight of 73 rodents; all
      were of the Apodemus flavicollis species. Partial sequences of the viral S-, M-,
      and L-genome segments were recovered and compared with previously reported DOBV
      sequences. The newly characterized Turkish strains were similar to other DOBV
      variants. Silent nucleotide mutations were dominant. The hantavirus prevalence in
      the Igneada region was similar to what has been reported in Greece and Bulgaria.
      For the first time, the M-segment sequences of DOBV from Turkey were recovered
      and genetic data of hantaviruses from Thrace region of Turkey were obtained.

PMID- 29377183
TI  - Identification of microRNAs as potential markers of ovarian toxicity.
AB  - Exposure to environmental toxicants has been associated with ovarian dysfunction
      yet sensitive biomarkers of adverse effect are lacking. We previously
      demonstrated that cigarette smoke exposure induced decreased relative ovarian
      weight, increased follicle loss and granulosa cell autophagy in mice. We
      postulate that cigarette smoke exposure will induce changes in the epigenome that
      can be used to reveal potential sensitive biomarkers of ovarian toxicity.
      Therefore, we evaluated differences in expression of 940 microRNAs (miRNAs),
      environmentally responsive small non-coding genes that regulate expression of
      genes at the post-transcriptional level, in ovarian tissue from 8-week-old female
      C57BL/6 mice exposed to room air or cigarette smoke 5 days per week for 8 weeks.
      A total of 152 miRNAs were dysregulated in expression, 17 of which were examined
      with quantitative polymerase chain reaction analysis. Using an online miRNA
      database tool, complete lists of predicted miRNA gene targets were generated, 12
      of which were measured for their expression levels with quantitative polymerase
      chain reaction. An online bioinformatics resource database, DAVID generated
      functional classification lists of the target genes and their associated
      biological pathways. Results of the present pilot study suggest that miR-379, miR
      15b, miR-691, miR-872 and miR-1897-5p are potentially useful markers of ovarian
      toxicity and dysfunction. Examination of the expression pattern of the target
      mRNA for these miRNA species demonstrated that cigarette smoke exposure induced
      significant changes that affect mitogen-activated protein kinase signaling
      pathways. We therefore suggest that miRNAs could serve as sensitive markers of
      ovarian toxicity and elucidate affected pathways.

PMID- 29377184
TI  - Relationship between mortality and rice cadmium concentration in inhabitants of
      the polluted Jinzu River basin, Toyama, Japan: A 26 year follow-up.
AB  - The aim of this study was to investigate the relationship between mortality and
      rice cadmium (Cd) concentration in inhabitants of a polluted area in Japan. The
      target subjects were inhabitants of the Jinzu River basin who participated in
      health examinations for screening of renal dysfunction from 1979 to 1984. The
      mean rice Cd concentration in each hamlet was used as an index of the Cd
      exposure. We conducted a 26 year follow-up survey in 3281 inhabitants (1544 men
      and 1737 women) whose data regarding the rice Cd concentration were available.
      Mortality risk ratios for all and specific causes were estimated after
      adjustments for age at baseline, smoking status and history of hypertension using
      a Cox hazard model or Fine and Gray competing risks regression model. The
      mortality risk ratios of rice Cd concentration (+0.1 ppm) for all causes in women
      were significantly increased (risk ratio: 1.04). Furthermore, the relative risks
      of rice Cd concentration for kidney and urinary tract disease, renal diseases,
      renal failure and toxic effects of cadmium were significantly increased in both
      sexes. These findings indicated that increased rice Cd concentration decreased
      the prognosis for life over a long-term observation in women. This result
      provides important information for determining the worldwide standard for
      allowable rice Cd concentration.

PMID- 29377185
TI  - In Vitro Comparison of Pediatric Oxygenators With and Without Integrated Arterial
      Filters in Maintaining Optimal Hemodynamic Stability and Managing Gaseous
      Microemboli.
AB  - The purpose of this study was to compare the Capiox FX15 oxygenator with
      integrated arterial filter to the Capiox RX15 oxygenator with separate Capiox
      AF125 arterial filter in terms of hemodynamic properties and gaseous microemboli
      (GME) capturing. Trials were conducted at varying flow rates (2.0 L/min, 3.0
      L/min, 4.0 L/min), temperatures (30 degrees C, 35 degrees C), and flow modalities
      (pulsatile, nonpulsatile). Pressure and flow waveforms were recorded using a
      custom-made data acquisition system. GME data were recorded using an Emboli
      Detection and Classification Quantifier after injecting a 5 mL air bolus into the
      venous line. Maximum instantaneous pre-oxygenator flows reached 7.4 L/min under
      pulsatile conditions when the roller pump was set to a flow rate of 4 L/min. Mean
      pressure drops were slightly greater in the FX15 group (P < 0.0001), and the
      diverted flow from the arterial purge line was slighter greater in the FX15 group
      at 3 L/min and 4 L/min (P < 0.0001). There was a slight generation of surplus
      hemodynamic energy (SHE) at the pre-oxygenator site for both oxygenators under
      "nonpulsatile mode." However, higher pre-oxygenator SHE levels were recorded for
      both groups with "pulsatile mode." The RX15 and FX15 groups were both able to
      remove all microemboli from the circuit at 2 L/min and 3 L/min in "nonpulsatile
      mode." Microemboli were delivered to the patient at 4 L/min with pulsatile flows
      in both groups. The RX15 oxygenator with separate AF125 arterial filter and FX15
      oxygenator with integrated arterial filter performed similarly in terms of
      hemodynamic performance and microemboli capturing. Pulsatile flows at 4 L/min
      produced instantaneous flow rates that surpassed the documented maximum flow
      rates of the oxygenators and might have contributed to the delivery of GME to the
      pseudo-patient.

PMID- 29377186
TI  - Positive stereotypes, negative outcomes: Reminders of the positive components of
      complementary gender stereotypes impair performance in counter-stereotypical
      tasks.
AB  - Gender stereotypes are complementary: Women are perceived to be communal but not
      agentic, whereas men are perceived to be agentic but not communal. The present
      research tested whether exposure to reminders of the positive components of these
      gender stereotypes can lead to stereotype threat and subsequent performance
      deficits on the complementary dimension. Study 1 (N = 116 female participants)
      revealed that compared to a control/no-stereotype condition, exposure to
      reminders of the stereotype about women's communality (but not to reminders of
      the stereotype about women's beauty) impaired women's math performance. In Study
      2 (N = 86 male participants), reminders of the stereotype about men's agency (vs.
      a control/no-stereotype condition) impaired men's performance in a test of socio
      emotional abilities. Consistent with previous research on stereotype threat, in
      both studies the effect was evident among participants with high domain
      identification. These findings extend our understanding of the potentially
      adverse implications of seemingly positive gender stereotypes.

PMID- 29377187
TI  - Evaluation of a laparoscopically assisted ovariectomy technique in cats.
AB  - OBJECTIVE: To describe a laparoscopically assisted ovariectomy (LAO) technique in
      the cat with a bipolar vessel sealing device (BVSD) or suture ligation and to
      compare the outcomes to open ovariohysterectomy (OO). STUDY DESIGN: Randomized
      prospective study ANIMALS: Healthy, adult, sexually intact female cats (n = 30).
      METHODS: Ten cats were assigned to each group: LAO with BVSD (group A), LAO with
      ligation (group B), and OO with ligation (group C). Surgical times and
      complications were assessed. Serum glucose and cortisol were measured prior to
      surgery and at 1, 2, 4, 6, 12, and 24 hours after surgery. Pain was scored by
      using an interactive visual analog scale (IVAS) at 0, 1, 2, 4, 6, 8, 12, 18, 24,
      36, and 48 hours after surgery. Rescue analgesia was provided when IVAS score was
      4 or more. Physiological and serum values and IVAS scores were compared among
      groups with area under the curve (AUC) by using a 1-way ANOVA. RESULTS: Surgical
      time was shortest for group C (19.1 +/- 5.2 minutes; P < .0002); there was no
      significant difference between groups A (27.7 +/- 6.6 minutes) and B (33.2 +/-
      8.2 minutes). All procedures were completed successfully. No significant
      differences among groups were found in IVAS scores (P = .36), rescue analgesia (P
      = .22), glucose AUC (P = .53), or cortisol AUC (P = .27). CONCLUSION: The LAO
      technique was accomplished as described in all cats with no complications or
      failures. Pain scores were not different from cats undergoing OO. LAO can be
      performed efficiently to maximize the benefits of minimally invasive surgery and
      is amenable to clinical practice.

PMID- 29377188
TI  - EARLY PARENTING SUPPORT AND INFORMATION: A CONSUMER PERSPECTIVE.
AB  - The transition to parenthood is a period of both joy and challenge for most
      parents. There is a recognized need to support parents during this period, yet
      existing interventions have shown limited evidence of efficacy. This study takes
      a consumer-focused approach to examine the needs and preferences of parents both
      prenatally (n = 77) and postnatally (n = 123) for parenting support. The study
      used a cross-sectional design with a purpose-built online survey. Parents were
      recruited via online forums, Facebook and parenting blogs, childcare centers, and
      playgroups. In general, all parents were satisfied with their current levels of
      both formal and informal support, and about one fourth of parents had accessed a
      parenting intervention. Parents expressed a moderate level of interest in
      additional parenting information, and parents expecting their first baby
      indicated preferences for information about basic baby care needs whereas
      postnatally, parents expressed more interest in topics around self-care and
      behavior management. The implications for developing interventions and engaging
      families are discussed.

PMID- 29377189
TI  - Systemic bone marker expression induced by grey and white mineral trioxide
      aggregate in normal and diabetic conditions.
AB  - AIM: To investigate the relationship between diabetes mellitus and local/systemic
      effects of both grey and white mineral trioxide aggregate (MTA) Angelus on bone
      marker expression. METHODOLOGY: Wistar rats were divided into two groups: healthy
      and diabetic (Alloxan induced), which were further divided into three subgroups
      (control, GMTA Angelus and WMTA Angelus). Polyethylene tubes filled with MTA
      materials or empty tubes were implanted in dorsal connective tissue. On days 7
      and 30, blood samples were collected for calcium, phosphorus and ALP measurement.
      The animals were euthanized; implanted tubes were removed and processed for
      immunohistochemical analysis of osteocalcin (OCN) and osteopontin (OPN). Kruskal
      Wallis followed by Dunn's multiple comparison test was performed for
      nonparametric data, and anova followed by Tukey's test for parametric data.
      RESULTS: No difference in systemic serum calcium levels between both groups was
      observed. On day 7, serum phosphorus levels within the WMTA healthy group were
      higher than that of the diabetic group. On day 30, healthy rats exhibited lower
      phosphorus levels than diabetic ones. At both time points, the diabetic group was
      associated with more ALP activity than the healthy group. Immunohistochemical
      analyses of the healthy group revealed OCN- and OPN-positive cells in the
      presence of both MTA materials. However, under diabetic conditions, both OCN and
      OPN were absent. CONCLUSION: Both MTA materials were associated with an increase
      in serum calcium, phosphorus and ALP, suggesting a potential systemic effect,
      along with triggered differentiation of OCN- and OPN-positive cells. Moreover, in
      diabetic conditions, an inhibitory effect on MTA-induced differentiation of OCN-
      and OPN-positive cells was detected.

PMID- 29377190
TI  - Human placental oxygenation in late gestation: experimental and theoretical
      approaches.
AB  - The placenta is crucial for life. It is an ephemeral but complex organ acting as
      the barrier interface between maternal and fetal circulations, providing exchange
      of gases, nutrients, hormones, waste products and immunoglobulins. Many gaps
      exist in our understanding of the detailed placental structure and function,
      particularly in relation to oxygen handling and transfer in healthy and
      pathological states in utero. Measurements to understand oxygen transfer in vivo
      in the human are limited, with no general agreement on the most appropriate
      methods. An invasive method for measuring partial pressure of oxygen in the
      intervillous space through needle electrode insertion at the time of Caesarean
      sections has been reported. This allows for direct measurements in vivo whilst
      maintaining near normal placental conditions; however, there are practical and
      ethical implications in using this method for determination of placental
      oxygenation. Furthermore, oxygen levels are likely to be highly heterogeneous
      within the placenta. Emerging non-invasive techniques, such as MRI, and ex vivo
      research are capable of enhancing and improving current imaging methodology for
      placental villous structure and increase the precision of oxygen measurement
      within placental compartments. These techniques, in combination with mathematical
      modelling, have stimulated novel cross-disciplinary approaches that could advance
      our understanding of placental oxygenation and its metabolism in normal and
      pathological pregnancies, improving clinical treatment options and ultimately
      outcomes for the patient.

PMID- 29377192
TI  - Monitoring pesticide residues in dates marketed in Al-Qassim, Saudi Arabia using
      a QuEChERS methodology and liquid chromatography-tandem mass spectrometry.
AB  - A sensitive, simple and rapid QuEChERS extraction method and liquid
      chromatography equipped with triple quadrupole mass spectrometry (LC-MS/MS) were
      used to determine 42 pesticides in dates. Acidified acetonitrile and citrate
      buffer salts were used to extract re-hydrated samples. Acceptable validation
      performances were achieved, i.e. recovery range of 70-120% and RSD values <=20%
      for 42 analytes at three different concentrations:100, 50 and 10 MUg/kg. This
      method was used to analyse 200 date fruit samples (var. Sukkari) collected from
      different large markets in the Al-Qassim region in Saudi Arabia. Pesticide
      residues were detected in 36 (18%) of the date fruits samples, and 15 samples
      (7.5%) exceeded the maximum residue levels. The ruggedness test results showed
      that this method is robust and suitable for the determination of pesticide
      residues in dates. Additionally, the results showed that the monitored dates did
      not have a health impact on consumers in Saudi Arabia during the study period.

PMID- 29377191
TI  - Psychometric properties of the PROMIS short form measures in a U.S. cohort of 961
      patients with chronic hepatitis C prescribed direct acting antiviral therapy.
AB  - BACKGROUND: To better understand symptoms experienced by patients infected with
      chronic hepatitis C virus (HCV), valid and reliable patient-reported outcome
      (PRO) measures are needed. AIM: To assess the reliability and validity of 10
      patient-reported outcomes measurement information system (PROMIS) measures and
      the Headache Impact Test-6 (HIT-6) in a large national sample of patients with
      HCV. METHODS: Pre-treatment data from 961 patients with HCV starting direct
      acting antiviral therapy at 11 U.S. liver centers were analyzed. Internal
      reliability was evaluated using Cronbach's alpha coefficient; frequency
      distributions were examined for floor and ceiling effects; structural validity
      was investigated via item-response-theory models; convergent validity was
      evaluated using correlations with theoretically-similar items from the HCV-PRO
      and memorial symptom assessment scale (MSAS); and known-groups validity was
      investigated by observing PRO differences by liver disease status and number of
      comorbidities. RESULTS: The HIT-6 and the majority of the PROMIS measures yielded
      excellent reliability (alphas >= 0.87). Ceiling effects were infrequent ( < 4%),
      while 30%-59% of patients reported no symptoms (floor effects). The data
      supported structural validity of the HIT-6 and most PROMIS measures. The PROMIS
      measures showed moderate to strong correlations with theoretically-similar items
      from the HCV-PRO and MSAS (0.39-0.77). Trends were observed between worse PRO
      scores and advanced cirrhosis and greater number of comorbidities, lending
      support for known-groups validity. CONCLUSIONS: The psychometric properties of
      the HIT-6 and PROMIS measures performed satisfactorily in this large cohort of
      patients with HCV starting direct acting antiviral therapy. Opportunities exist
      for further refinement of these PROs. Evaluation of performance over time and in
      under-represented subgroups is needed.

PMID- 29377193
TI  - Von Willebrand factor indicates bacterial translocation, inflammation, and
      procoagulant imbalance and predicts complications independently of portal
      hypertension severity.
AB  - BACKGROUND: Elevated plasma von Willebrand factor antigen (vWF) has been shown to
      indicate the presence of clinically significant portal hypertension, and thus,
      predicts the development of clinical events in patients with cirrhosis. AIM: To
      investigate the impact of bacterial translocation and inflammation on vWF, as
      well as the association between vWF and procoagulant imbalance. Moreover, we
      assessed whether vWF predicts complications of cirrhosis, independent of the
      severity of portal hypertension. METHODS: Our study population comprised 225
      patients with hepatic venous pressure gradient (HVPG) >= 10 mm Hg without active
      bacterial infections or hepatocellular carcinoma. RESULTS: vWF correlated with
      markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; rho
      = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; rho = 0.426; P < 0.001]
      and C-reactive protein [CRP; rho = 0.249; P < 0.001]), and procoagulant imbalance
      (factor VIII/protein C ratio; rho = 0.507; P < 0.001). Importantly, the
      associations between vWF and these parameters were independent of HVPG. Moreover,
      vWF (per 10%) independently predicted variceal bleeding (hazard ratio [HR]: 1.08
      [95% confidence interval (95% CI): 1.01-1.16]; P = 0.023), requirement of
      paracentesis (HR: 1.05 [95% CI: 1.01-1.1]; P = 0.023) and bacterial infections
      (HR: 1.04 [95% CI: 1-1.09]; P = 0.04) including spontaneous bacterial peritonitis
      (HR: 1.09 [95% CI: 0.999-1.18]; P = 0.053) on a trend-wise level. After backward
      elimination, vWF (HR: 1.05 [95% CI: 1.02-1.08]; P = 0.003) and CRP (per 10 mg/L;
      HR: 1.53 [95% CI: 1.14-2.05]; P = 0.005) remained in the final model for
      transplant-free mortality. Finally, the independent prognostic value of vWF/CRP
      groups for mortality was confirmed by competing risk analysis. CONCLUSION: Our
      results demonstrate that vWF is not only a marker of portal hypertension but also
      independently linked to bacterial translocation, inflammation and procoagulant
      imbalance, which might explain its HVPG-independent association with most
      clinical events. Prognostic groups based on vWF/CRP efficiently discriminate
      between patients with a poor 5-year survival and patients with a favourable
      prognosis.

PMID- 29377194
TI  - Effect of ultraviolet irradiation on free radical scavenging activity of
      immunosuppressants used in lung transplantation and comparative electron
      paramagnetic resonance study of kinetics of their interactions with model free
      radicals.
AB  - WHAT IS KNOWN AND OBJECTIVE: The immunosuppressive drugs used in solid organ
      transplantation or autoimmunological processes were studied by electron
      paramagnetic resonance (EPR) spectroscopy to estimate their free radical
      scavenging activity. The interactions of immunosuppressants with free radicals
      were examined by an X-band (9.3 GHz) EPR spectroscopy and a model of DPPH free
      radicals. METHODS: The EPR spectra of DPPH and DPPH interacting with individual
      drugs were compared. Kinetic studies were performed, and the effect of
      ultraviolet (UV) irradiation on the free radical scavenging activity of the
      tested drugs was determined. RESULTS AND DISCUSSION: The free radical scavenging
      activity of non-irradiated drugs decreased in the order: rapamycin >
      mycophenolate mofetil > ciclosporin > tacrolimus. UV irradiation increased the
      free radical scavenging activity of all the tested immunosuppressive drugs, and
      the effect was highest for tacrolimus. For the non-irradiated samples, the speed
      of free radical interactions decreased in the order: ciclosporin > tacrolimus >
      mycophenolate mofetil > rapamycin. UV irradiation only slightly affected the
      speed of interactions of the immunosuppressive drugs with the model DPPH free
      radicals. WHAT IS NEW AND CONCLUSION: Electron paramagnetic resonance
      spectroscopy is useful for obtaining information on interactions of
      immunosuppressive drugs with free radicals. We hypothesized that the long-term
      immunosuppressive effects of these drugs after transplantation or during
      autoimmune disorders may be mediated by anti-inflammatory action in addition to
      the known receptor/cell cycle inhibition.

PMID- 29377195
TI  - Lognormal Approximations of Fault Tree Uncertainty Distributions.
AB  - Fault trees are used in reliability modeling to create logical models of fault
      combinations that can lead to undesirable events. The output of a fault tree
      analysis (the top event probability) is expressed in terms of the failure
      probabilities of basic events that are input to the model. Typically, the basic
      event probabilities are not known exactly, but are modeled as probability
      distributions: therefore, the top event probability is also represented as an
      uncertainty distribution. Monte Carlo methods are generally used for evaluating
      the uncertainty distribution, but such calculations are computationally intensive
      and do not readily reveal the dominant contributors to the uncertainty. In this
      article, a closed-form approximation for the fault tree top event uncertainty
      distribution is developed, which is applicable when the uncertainties in the
      basic events of the model are lognormally distributed. The results of the
      approximate method are compared with results from two sampling-based methods:
      namely, the Monte Carlo method and the Wilks method based on order statistics. It
      is shown that the closed-form expression can provide a reasonable approximation
      to results obtained by Monte Carlo sampling, without incurring the computational
      expense. The Wilks method is found to be a useful means of providing an upper
      bound for the percentiles of the uncertainty distribution while being
      computationally inexpensive compared with full Monte Carlo sampling. The
      lognormal approximation method and Wilks's method appear attractive, practical
      alternatives for the evaluation of uncertainty in the output of fault trees and
      similar multilinear models.

PMID- 29377196
TI  - Direct-acting antiviral sustained virologic response: Impact on mortality in
      patients without advanced liver disease.
AB  - : The impact of sustained virologic response (SVR) on mortality after direct
      acting antiviral (DAA) treatment is not well documented in patients without
      advanced liver disease and affects access to treatment. This study evaluated the
      impact of SVR achieved with interferon-free DAA treatment on all-cause mortality
      in hepatitis C virus-infected patients without advanced liver disease. This
      observational cohort analysis was comprised of 103,346 genotype 1, 2, and 3,
      hepatitis C virus-monoinfected patients without advanced liver disease, defined
      by FIB-4 <=3.25 and no diagnosis of cirrhosis, hepatic decompensation, or
      hepatocellular carcinoma or history of liver transplantation, identified from the
      Veterans Affairs Hepatitis C Clinical Case Registry. Among 40,664 patients
      treated with interferon-free DAA regimens, 39,374 (96.8%) achieved SVR and 1,290
      (3.2%) patients were No SVR; 62,682 patients constituted the untreated cohort.
      The mortality rate for SVR patients of 1.18 deaths/100 patient-years was
      significantly lower than the rates for both No SVR patients (2.84 deaths/100
      patient-years; P < 0.001) and untreated patients (3.84 deaths/100 patient-years;
      P < 0.001). SVR patients with FIB-4 <1.45 and 1.45-3.25 had a 46.0% (P = 0.036)
      and 63.2% (P < 0.001) reduction in mortality rates, respectively, compared to No
      SVR patients and 66.7% (P < 0.001) and 70.6% (P < 0.001) reduction in mortality
      rates, respectively, compared to untreated patients. In multivariate Cox
      proportional hazard models controlling for baseline demographics, clinical
      characteristics, and comorbidities, SVR was independently associated with reduced
      risk of death compared to No SVR (hazard ratio, 0.44; 95% confidence interval,
      0.32-0.59; P < 0.001) and compared to untreated patients (hazard ratio, 0.32; 95%
      confidence interval, 0.29-0.36; P < 0.001). CONCLUSION: Successfully treating
      hepatitis C virus with DAAs in patients without clinically apparent advanced
      liver disease translates into a significant mortality benefit. (Hepatology 2018).

PMID- 29377197
TI  - Visible Light-Induced Radical Mediated DNA Damage.
AB  - Light-responsive compounds have been used to manipulate biological systems with
      spatial and temporal control of the event of interest. Illumination of
      alkylcobalamins with green light (>500 nm) produces carbon-centered radicals,
      which have been demonstrated to effectively cause DNA damage. Molecules that
      cause DNA and RNA strand scission are useful for studying polynucleotide
      structure and the binding of small molecules and proteins to polynucleotides.
      Most molecules that cause DNA damage in a light-dependent manner require high
      energy, short wavelength ultraviolet light, which is readily absorbed by
      nucleotide bases causing damage to the polynucleotides. Therefore, using
      alkylcobalamins is advantageous for causing strand scission of polynucleotides,
      because they are activated by light wavelengths that are not absorbed by
      nucleotide bases. Green-light illumination of methylcobalamin effectively causes
      DNA strand scission based on gel mobility assays. This cleavage is due to the
      generation of carbon-centered radicals based on the results of a radical trapping
      study. In addition, synthesis of an alkylcobalamin with a DNA binding moiety,
      spermine, improves DNA cleavage efficacy by an order of magnitude in comparison
      with methylcobalamin.

PMID- 29377198
TI  - Updates on obesity pharmacotherapy.
AB  - Obesity is a chronic, relapsing disease that necessitates a multidisciplinary
      approach to management. Behavioral changes are the foundation to management, but
      adjunctive therapy is often warranted, including pharmacologic therapies and/or
      bariatric surgery. Until recently, treatment options included only short-term
      therapy (<=12 weeks), and paths beyond that schedule were challenging, as
      knowledge of the biology of obesity was lacking. With increased recognition of
      obesity as a chronic, complex medical disease, newer agents have been approved as
      long-term therapy, and the cornerstone of treatment is chronic behavior and
      lifestyle change. In the last decade, the Food and Drug Administration (FDA) has
      approved several new weight loss medications for the chronic management of
      obesity. In this review paper, we provide the latest updates on obesity
      pharmacotherapy. The main areas we will cover include (1) pharmacological
      management of obesity, (2) a review of FDA-approved weight loss medications, (3)
      comanagement of obesity and its metabolic sequelae (type 2 diabetes mellitus,
      hypertension, and dyslipidemia), and (4) obesity-centric prescribing for mental
      illness, neurological disorders, and contraceptive planning.

PMID- 29377199
TI  - Piecing together the puzzle of pancreatic islet adaptation in pregnancy.
AB  - Pregnancy places acute demands on maternal physiology, including profound changes
      in glucose homeostasis. Gestation is characterized by an increase in insulin
      resistance, counterbalanced by an adaptive increase in pancreatic beta cell
      production of insulin. Failure of normal adaptive responses of the islet to
      increased maternal and fetal demands manifests as gestational diabetes mellitus
      (GDM). The gestational changes and rapid reversal of islet adaptations following
      parturition are at least partly driven by an anticipatory program rather than
      post-factum compensatory adaptations. Here, I provide a comprehensive review of
      the cellular and molecular mechanisms underlying normal islet adaptation during
      pregnancy and how dysregulation may lead to GDM. Emerging areas of interest and
      understudied areas worthy of closer examination in the future are highlighted.

PMID- 29377200
TI  - Precision medicine in diabetes: an opportunity for clinical translation.
AB  - Metabolic disorders present a public health challenge of staggering proportions.
      In diabetes, there is an urgent need to better understand disease heterogeneity,
      clinical trajectories, and related comorbidities. A pressing and timely question
      is whether we are ready for precision medicine in diabetes. Some biological
      insights that have emerged during the last decade have already been used to
      direct clinical decision making, especially in monogenic forms of diabetes.
      However, much work is necessary to integrate high-dimensional explorations into
      complex disease architectures, less penetrant biological alterations, and broader
      phenotypes, such as type 2 diabetes. In addition, for precision medicine to take
      hold in diabetes, reproducibility, interpretability, and actionability remain key
      guiding objectives. In this review, we examine how mounting data sets generated
      during the last decade to understand biological variability are now inspiring new
      venues to clarify diabetes nosology and ultimately translate findings into more
      effective prevention and treatment strategies.

PMID- 29377203
TI  - Media Smart-Targeted: Diagnostic outcomes from a two-country pragmatic online
      eating disorder risk reduction trial for young adults.
AB  - BACKGROUND: Diagnostic outcomes in eating disorder (ED) risk reduction trials are
      important but rarely reported. METHODS: An online pragmatic randomized-controlled
      trial was conducted with young-adult women in Australia and New Zealand seeking
      to improve their body image. Media Smart-Targeted (MS-T) was a 9-module program
      released weekly while control participants received tips for positive body image.
      Eating Disorder Examination-Questionnaire (EDE-Q) scores from baseline and 12
      month follow-up were used to investigate two outcomes: ED onset in those who were
      asymptomatic at baseline (prevention effects); and, ED remission in those who met
      diagnosis at baseline (treatment effects). RESULTS: MS-T participants were 66%
      less likely than controls to develop an ED by 12-month follow-up
      (nonsignificant). MS-T participants who met ED criteria at baseline were 75% less
      likely than controls to still meet diagnostic criteria at follow-up. This effect
      was significant and remained so for both those who did and who did not access
      external face-to-face ED treatment during the trial. CONCLUSIONS: While further
      investigations are necessary, MS-T has fully automated procedures, low
      implementation costs, the potential to be delivered at-scale to assist those
      assist those where face-to-face services are limited or not available (e.g.,
      remote areas).

PMID- 29377204
TI  - Meta-Analysis of Early Enteral Nutrition Provided Within 24 Hours of Admission on
      Clinical Outcomes in Acute Pancreatitis.
AB  - BACKGROUND: Enteral nutrition (EN) is more beneficial than parenteral nutrition
      (PN) in reducing organ failure, infectious complications, and mortality of acute
      pancreatitis (AP), but its timing is controversial. We attempted to evaluate the
      safety and clinical outcomes of early EN within 24 hours of admission in patients
      with AP, especially in predicted severe or severe acute pancreatitis (SAP).
      METHODS: We searched PubMed, EMBASE Databases, Web of Science, and the Cochrane
      Library for relevant articles before June 2016 using RevMan 5.2 software.
      RESULTS: Eight studies containing 727 patients with AP were analyzed in the meta
      analysis. Comparing early EN to late EN or total parental nutrition in AP, the
      odds ratios (OR) were 0.56 (95% CI 0.23 -1.34) for the risk of mortality, 0.40
      (95% CI 0.20-0.79) for multiple organ failure, 0.57 (95% CI 0.23-1.42) for
      infectious complications, 0.45 (95% CI 0.17-1.21) for adverse events, and 0.83
      (95% CI 0.59-1.18) for pancreatic-related infections. Furthermore, subgroup
      analysis for early EN in predicted severe or SAP showed a significant reduction
      in multiple organ failure (OR 0.30; 95% CI 0.09-0.96) and pancreatic-related
      infections (OR 0.51, 95% CI 0.29-0.88). Early EN provided no benefits for mild to
      moderate AP. CONCLUSION: Early EN within 24 hours of admission is safe and
      provides benefits for predicted severe or SAP, but not for mild to moderate
      pancreatitis.

PMID- 29377202
TI  - Update on management of diabetic foot ulcers.
AB  - Diabetic foot ulcers (DFUs) are a serious complication of diabetes that results
      in significant morbidity and mortality. Mortality rates associated with the
      development of a DFU are estimated to be 5% in the first 12 months, and 5-year
      morality rates have been estimated at 42%. The standard practices in DFU
      management include surgical debridement, dressings to facilitate a moist wound
      environment and exudate control, wound off-loading, vascular assessment, and
      infection and glycemic control. These practices are best coordinated by a
      multidisciplinary diabetic foot wound clinic. Even with this comprehensive
      approach, there is still room for improvement in DFU outcomes. Several adjuvant
      therapies have been studied to reduce DFU healing times and amputation rates. We
      reviewed the rationale and guidelines for current standard of care practices and
      reviewed the evidence for the efficacy of adjuvant agents. The adjuvant therapies
      reviewed include the following categories: nonsurgical debridement agents,
      dressings and topical agents, oxygen therapies, negative pressure wound therapy,
      acellular bioproducts, human growth factors, energy-based therapies, and systemic
      therapies. Many of these agents have been found to be beneficial in improving
      wound healing rates, although a large proportion of the data are small,
      randomized controlled trials with high risks of bias.

PMID- 29377201
TI  - Cardiometabolic risk in obese children.
AB  - Obesity in childhood remains a significant and prevalent public health concern.
      Excess adiposity in youth is a marker of increased cardiometabolic risk (CMR) in
      adolescents and adults. Several longitudinal studies confirm the strong
      association of pediatric obesity with the persistence of adult obesity and the
      future development of cardiovascular disease, diabetes, and increased risk of
      death. The economic and social impact of childhood obesity is further exacerbated
      by the early onset of the chronic disease burden in young adults during their
      peak productivity years. Furthermore, rising prevalence rates of severe obesity
      in youth from disadvantaged and/or minority backgrounds have prompted the
      creation of additional classification schemes for severe obesity to improve CMR
      stratification. Current guidelines focus on primary obesity prevention efforts,
      as well as screening for clustering of multiple CMR factors to target
      interventions. This review summarizes the scope of the pediatric obesity
      epidemic, the new severe obesity classification scheme, and examines the
      association of excess adiposity with cardiovascular and metabolic risk. We will
      also discuss potential questions for future investigation.

PMID- 29377205
TI  - Effect of titanium ions on the Hippo/YAP signaling pathway in regulating
      biological behaviors of MC3T3-E1 osteoblasts.
AB  - Titanium (Ti) and its corresponding alloys have been widely applied in dental and
      orthopedic implants. Owing to abrasion and corrosion of implants in the
      unfavorable electrolytic aqueous environment of the host body, Ti ions could be
      released from implants and accumulated in local tissues. Recent studies have
      found that excessive Ti ions were toxic to osteoblasts in adjacent bone tissues
      and subsequently influenced long-term effects on implant prostheses. However, the
      potential molecular mechanisms underlying the damage to osteoblasts induced by Ti
      ions remained unclear. Hippo signaling has been confirmed to be involved in organ
      size and tissue regeneration in many organs, while its roles in osteoblasts
      differentiation and bone repair remained elusive. Therefore, we hypothesize that
      YAP, a regulator of Hippo pathway, inhibited osteoblast growth, skeletal
      development and bone repair, as well as excessive Ti ions promoted the
      progression of YAP activation. This study aimed to explore the role of Hippo/YAP
      signaling pathway in the biotoxicity effect of Ti ions on osteoblast behaviors.
      Here, we confirmed that 10 ppm Ti ions, a minimum concentration gradient
      previously reported that was capable of suppressing osteoblasts growth, induced
      nuclear expression of YAP in osteoblasts in our study. Furthermore, 10 ppm Ti ion
      induced YAP activation was found to downregulate osteogenic differentiation of
      MC3T3-E1 cells. Most importantly, the hypothesis we proposed that knockdown of
      YAP did reverse the inhibitory effect of 10 ppm Ti ions on osteogenesis has been
      verified. Taken together, our work provides insights into the mechanism of which
      YAP is involved in regulating osteoblast behaviors under the effect of Ti ions,
      which may help to develop therapeutic applications for Ti implant failures and
      peri-implantitis.

PMID- 29377206
TI  - Reply.

PMID- 29377207
TI  - Farnesoid X receptor signaling activates the hepatic X-box binding protein 1
      pathway in vitro and in mice.
AB  - : Bile acids are endogenous ligands of the nuclear receptor, farnesoid X receptor
      (FXR), and pharmacological FXR modulators are under development for the treatment
      of several liver disorders. The inositol-requiring enzyme 1alpha/X-box binding
      protein 1 (IRE1alpha/XBP1) pathway of the unfolded protein response (UPR) is a
      protective cellular signaling pathway activated in response to endoplasmic
      reticulum (ER) stress. We investigated the role of FXR signaling in activation of
      the hepatic XBP1 pathway. Mice were treated with deoxycholic acid (DCA),
      cholestyramine, GW4064, or underwent bile duct ligation (BDL), and hepatic UPR
      activation was measured. Huh7-Ntcp and HepG2 cells were treated with FXR
      agonists, inhibitor, small interfering RNA (siRNA), or small heterodimer partner
      (SHP) siRNA to determine the mechanisms of IRE1alpha/XBP1 pathway activation. DCA
      feeding and BDL increased and cholestyramine decreased expression of hepatic XBP1
      spliced (XBP1s). XBP1 pathway activation increased in Huh7-Ntcp and HepG2 cells
      treated with bile acids, 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA) or GW4064.
      This effect decreased with FXR knockdown and treatment with the FXR inhibitor
      guggulsterone. FXR agonists increased XBP1 splicing and phosphorylated IRE1alpha
      (p-IRE1alpha) expression. Overexpression of SHP similarly increased XBP1
      splicing, XBP1s, and p-IRE1alpha protein expression. SHP knockdown attenuated FXR
      agonist-induced XBP1s and p-IRE1alpha protein expression. Co-immunoprecipitation
      (Co-IP) assays demonstrate a physical interaction between overexpressed green
      fluorescent protein (GFP)-SHP and FLAG-IRE1alpha in HEK293T cells. Mice treated
      with GW4064 had increased, and FXR and SHP null mice had decreased, basal Xbp1s
      gene expression. CONCLUSION: FXR signaling activates the IRE1alpha/XBP1 pathway
      in vivo and in vitro. FXR pathway activation increases XBP1 splicing and enhances
      p-IRE1alpha expression. These effects are mediated, at least in part, by SHP.
      IRE1alpha/XBP1 pathway activation by bile acids and pharmacological FXR agonists
      may be protective during liver injury and may have therapeutic implications for
      liver diseases. (Hepatology 2018;68:304-316).

PMID- 29377208
TI  - Carcinoembryonic antigen-related cell adhesion molecule 1 controls IL-2-dependent
      regulatory T-cell induction in immune-mediated hepatitis in mice.
AB  - : A dysbalance between effector T cells (Tconv) and regulatory T cells (Tregs)
      and impaired Treg function can cause autoimmune liver disease. Therefore, it is
      important to identify molecular mechanisms that control Treg homeostasis.
      Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66a) is an
      immune coreceptor with dichotomous roles in T-cell regulation: its short isoform
      (CEACAM1S) can activate T cells and induce Tregs, whereas its long isoform
      (CEACAM1L), containing two intracellular immune receptor tyrosine-based
      inhibitory motifs, can inhibit activated T-cell function. In the liver, CEACAM1
      has antifibrotic effects in models of nonalcoholic steatohepatitis. However, its
      role in immune-mediated hepatitis is unknown. In the mouse model of concanavalin
      A-induced CD4+ T-cell-dependent liver injury, liver damage was aggravated and
      persisted in Ceacam1-/- mice. Concomitantly, we observed hyperexpansion of Tconv,
      but reduction of interleukin (IL)-2 production and hepatic forkhead box protein
      P3+ (Foxp3+ )CD4+ Treg numbers. CEACAM1-/- CD4+ T cells showed impaired IL-2
      mediated signal transducer and activator of transcription 5 (STAT5)
      phosphorylation, which correlated with a failure of naive CEACAM1-/- CD4+ T cells
      to convert into Tregs in vitro. Furthermore, CEACAM1-/- Tregs expressed reduced
      levels of Foxp3, CD25, and B-cell lymphoma 2. Adoptive transfer experiments
      demonstrated that hepatic Treg expansion and suppressive activity required
      CEACAM1 expression on both CD4+ T cells and Tregs. We identified predominant
      CEACAM1S expression on hepatic CD4+ T cells and Tregs from mice with acute liver
      injury and expression of both isoforms in liver-derived CD4+ T-cell clones from
      patients with liver injury. CONCLUSION: Our data suggest that CEACAM1S expression
      in CD4+ T cells augments IL-2 production and STAT5 phosphorylation leading to
      enhanced Treg induction and stability, which, ultimately, confers protection from
      T-cell-mediated liver injury. (Hepatology 2018;68:200-214).

PMID- 29377210
TI  - A Comprehensive Risk Analysis of Transportation Networks Affected by Rainfall
      Induced Multihazards.
AB  - Climate change and its projected natural hazards have an adverse impact on the
      functionality and operation of transportation infrastructure systems. This study
      presents a comprehensive framework to analyze the risk to transportation
      infrastructure networks that are affected by natural hazards. The proposed risk
      analysis method considers both the failure probability of infrastructure
      components and the expected infrastructure network efficiency and capacity loss
      due to component failure. This comprehensive approach facilitates the
      identification of high-risk network links in terms of not only their
      susceptibility to natural hazards but also their overall impact on the network.
      The Chinese national rail system and its exposure to rainfall-related
      multihazards are used as a case study. The importance of various links is
      comprehensively assessed from the perspectives of topological, efficiency, and
      capacity criticality. Risk maps of the national railway system are generated,
      which can guide decisive action regarding investments in preventative and
      adaptive measures to reduce risk.

PMID- 29377211
TI  - A novel frailty index improves risk prediction of waitlist mortality over the
      model for end-stage liver disease score alone.

PMID- 29377212
TI  - You don't always get what you want: Does hypoxia cause sickle cell crisis?

PMID- 29377209
TI  - Should vitamin B12 status be considered in assessing risk of neural tube defects?
AB  - There is a strong biological premise for including vitamin B12 with folic acid in
      strategies to prevent neural tube defects (NTDs), due to the closely interlinked
      metabolism of these two vitamins. For example, reduction of B12 deficiency among
      women of reproductive age could enhance the capacity of folic acid to prevent
      NTDs by optimizing the cellular uptake and utilization of natural folate
      cofactors. Vitamin B12 might also have an independent role in NTD prevention,
      such that adding it in fortification programs might be more effective than
      fortifying with folic acid alone. Globally, there is ample evidence of widespread
      vitamin B12 deficiency in low- and middle-income countries, but there is also
      considerable divergence of vitamin B12 status across regions, likely due to
      genetic as well as nutritional factors. Here, I consider the evidence that low
      vitamin B12 status may be an independent factor associated with risk of NTDs, and
      whether a fortification strategy to improve B12 status would help reduce the
      prevalence of NTDs. I seek to identify knowledge gaps in this respect and specify
      research goals that would address these gaps.

PMID- 29377213
TI  - Reply to "a novel mutation in the transmembrane 6 domain of GABBR2 leads to a
      rett-like phenotype".

PMID- 29377215
TI  - Reply.

PMID- 29377216
TI  - The Safety and Efficacy of Low-Dose Naltrexone in the Management of Chronic Pain
      and Inflammation in Multiple Sclerosis, Fibromyalgia, Crohn's Disease, and Other
      Chronic Pain Disorders.
AB  - Chronic inflammatory diseases are complex to treat and have an impact on a large
      number of patients. Due to the difficulty of treating these diseases and the
      great impact on quality of life, patients often seek off-label, complimentary, or
      alternative medicines to gain relief from symptoms. Low-dose naltrexone has been
      used off-label for treatment of pain and inflammation in multiple sclerosis,
      Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid
      receptor antagonist indicated by the U.S. Food and Drug Administration for opioid
      and alcohol dependence. It is hypothesized that lower than standard doses of
      naltrexone inhibit cellular proliferation of T and B cells and block Toll-like
      receptor 4, resulting in an analgesic and antiinflammatory effect. It is the
      purpose of this review to examine the evidence of the safety, tolerability, and
      efficacy of low-dose naltrexone for use in chronic pain and inflammatory
      conditions. Currently, evidence supports the safety and tolerability of low-dose
      naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer
      studies support the efficacy of low-dose naltrexone, with most of these focusing
      on subjective measures such as quality of life or self-reported pain. These
      studies do demonstrate that low-dose naltrexone has subjective benefits over
      placebo, but evidence for more objective measures is limited. However, further
      randomized controlled trials are needed to determine the efficacy of low-dose
      naltrexone due to insufficient evidence supporting its use in these disease
      states. This review provides practitioners with the extent of low-dose naltrexone
      evidence so that they can be cognizant of situations where it may not be the most
      appropriate therapy.

PMID- 29377217
TI  - Reaction of 11 C-benzoyl chlorides with metalloid reagents: 11 C-labeling of
      benzyl alcohols, benzaldehydes, and phenyl ketones from [11 C]CO.
AB  - In this article, we describe the carbon-11 (11 C, t1/2  = 20.4 minutes) labeling
      of benzyl alcohols, benzaldehydes, and ketones using an efficient 2-step
      synthesis in which 11 C-carbon monoxide is used in an initial palladium-mediated
      reaction to produce 11 C-benzoyl chloride as a key intermediate. In the second
      step, the obtained 11 C-benzoyl chloride is further treated with a metalloid
      reagent to furnish the final 11 C-labeled product. Benzyl alcohols were obtained
      in moderated to high non-isolated radiochemical yields (RCY, 35%-90%) with
      lithium aluminum hydride or lithium aluminum deuteride as metalloid reagent.
      Changing the metalloid reagent to either tributyltin hydride or sodium
      borohydride, allowed for the reliable syntheses of 11 C-benzaldehydes in RCYs
      ranging from 58% to 95%. Finally, sodium tetraphenylborate were utilized to
      obtain 11 C-phenyl ketones in high RCYs (77%-95%). The developed method provides
      a new and efficient route to 3 different classes of compounds starting from aryl
      iodides or aryl bromides.

PMID- 29377218
TI  - Does public transportation improve the accessibility of primary dental care in
      Sao Paulo, Brazil?
AB  - OBJECTIVE: Advances in geospatial technologies have recognized the role of
      geographic distance as a barrier to healthcare accessibility. Frequent
      transportation is supposed to buffer issues with distance, while infrequent
      services impede the uptake of care. The role of public transportation on the
      accessibility of health care-including oral health care-is not well elucidated in
      the context of megacities, such as the municipality of Sao Paulo, Brazil. This
      study aimed to compare the supply of public transportation to primary dental
      clinics and the population between advantaged and disadvantaged areas in Sao
      Paulo city. METHODS: A total of 4101 primary dental clinics in Sao Paulo city
      were identified and geocoded. Geographic coordinates were also retrieved for the
      19 242 bus stops, 56 commuter rail stations and 64 rapid transit stations. Clinic
      locations and transport points were integrated with the city's 19 128 constituent
      census tracts-each containing sociodemographic data on the 11 252 204 residents
      using Geographic Information Systems (GIS). RESULTS: Almost all clinics were
      located within 0.5 km of public transportation. Half of all clinics were within
      0.5 km of high-frequency transport points, and three-quarters were within 1 km.
      Likewise, 99% of the population resided within 0.5 km of any public
      transportation. However, only 22% were within 0.5 km of high-frequency options,
      and half were within 1 km. Those within 0.5 km of high-frequency points had
      higher average monthly household incomes and lower illiteracy rates, with lower
      proportions of children and ethnic minorities, and higher proportions of older
      people. CONCLUSION: Clinics and populations in sociodemographically disadvantaged
      tracts have poorer public transportation links in Sao Paulo city.

PMID- 29377214
TI  - Western lifestyle and immunopathology of multiple sclerosis.
AB  - There is increasing evidence for a sudden and unprecedented rise in the incidence
      of multiple sclerosis (MS) in Westernized countries over the past decades,
      emphasizing the role of environmental factors. Among many candidates, rapid
      changes in dietary habits seem to play a role in the pathogenesis of MS. Here, we
      summarize and discuss the available evidence for the role of dietary nutrients,
      such as table salt, fatty acids, and flavonoids, in the development and
      pathogenesis of MS. We also discuss new and emerging risk factors accompanying
      Western lifestyle, such as shift work, sleep, and circadian disruption.

PMID- 29377219
TI  - Alterations in wheat pollen lipidome during high day and night temperature
      stress.
AB  - Understanding the adaptive changes in wheat pollen lipidome under high
      temperature (HT) stress is critical to improving seed set and developing HT
      tolerant wheat varieties. We measured 89 pollen lipid species under optimum and
      high day and/or night temperatures using electrospray ionization-tandem mass
      spectrometry in wheat plants. The pollen lipidome had a distinct composition
      compared with that of leaves. Unlike in leaves, 34:3 and 36:6 species dominated
      the composition of extraplastidic phospholipids in pollen under optimum and HT
      conditions. The most HT-responsive lipids were extraplastidic phospholipids,
      phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol,
      phosphatidic acid, and phosphatidylserine. The unsaturation levels of the
      extraplastidic phospholipids decreased through the decreases in the levels of
      18:3 and increases in the levels of 16:0, 18:0, 18:1, and 18:2 acyl chains. PC
      and PE were negatively correlated. Higher PC:PE at HT indicated possible PE-to-PC
      conversion, lower PE formation, or increased PE degradation, relative to PC.
      Correlation analysis revealed lipids experiencing coordinated metabolism under HT
      and confirmed the HT responsiveness of extraplastidic phospholipids. Comparison
      of the present results on wheat pollen with results of our previous research on
      wheat leaves suggests that similar lipid changes contribute to HT adaptation in
      both leaves and pollen, though the lipidomes have inherently distinct
      compositions.

PMID- 29377220
TI  - Von Willebrand factor for the liver: Friend or foe?

PMID- 29377221
TI  - Sox10 positive breast carcinoma metastatic to the skin.

PMID- 29377222
TI  - Assessment of a training programme on detection of temporomandibular joint
      osseous changes applying pre-defined 2D multiplane cone beam computed tomography
      reconstructions.
AB  - OBJECTIVES: Osseous changes in temporomandibular joint disorders (TMD) are common
      indications for cone beam computed tomography (CBCT). The number of such cases is
      increasing while a number of qualified oral radiologists is limited. This study
      investigated the usefulness of a training programme for general dental
      practitioners (GDPs) regarding temporomandibular joint (TMJ) osseous changes
      detection in CBCT images. METHODS: We selected CBCT images of 35 TMD cases and
      chose 5 of them to use in training 7 GDPs on detecting osseous changes in the
      TMJ. In evaluation directly following training, GDPs assessed the 30 remaining
      cases. Three qualified radiologists served as reference standard. A 2-month
      follow-up of training comprising evaluation of the same cases. The cases are
      assessed according to Ahmad et al (Oral Surg Oral Med Oral Pathol Oral Radiol
      Endod, 107, 2009, 844) protocol of TMJ osseous changes in CBCT images. RESULTS:
      Sensitivity and specificity of the CBCT protocol were high, except for some
      criteria that did not appear in the cases. Average observer sensitivity was 65%
      while specificity was 87%. Average correct individual response rate was 84%. Mean
      agreement among the GDPs was 73%. Observer performance had improved at the 2
      month follow-up. CONCLUSION: The present educational programme could be a helpful
      material on recognising possible osseous changes of TMJ and it can be used as a
      part of a training programme for GDP and for specialist candidates.

PMID- 29377223
TI  - Exploring sand fly salivary proteins to design multiepitope subunit vaccine to
      fight against visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is caused by the parasites of Leishmania donovani
      complex, leads to the death of 20 000 to 40 000 people from 56 affected
      countries, worldwide. Till date, there is not a single available vaccine
      candidate to prevent the VL infection, and treatment only relies upon expensive
      and toxic chemotherapeutic options. Consequently, immunoinformatics approach was
      applied to design a multiepitope-based subunit vaccine to enhance the humoral as
      well as cell-mediated immunity. Constructed vaccine candidate was further
      subjected to evaluation on allergenicity and antigenicity and physiochemical
      parameters. Later on, disulfide engineering was performed to increase the
      stability of vaccine construct. Also, molecular docking and molecular dynamics
      simulation study were performed to check the binding affinity and stability of
      toll-like receptor-4 to vaccine construct complex. Finally, codon optimization
      and in silico cloning were performed to ensure the expression of proposed vaccine
      construct in a microbial expression system.

PMID- 29377224
TI  - Thrombotic microangiopathy in the setting of human immunodeficiency virus
      infection: High incidence of severe thrombocytopenia.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection increases the risk of
      thrombotic microangiopathy (TMA), but TMA in the setting of HIV infection is not
      well characterized. The experience with TMA in the setting of HIV infection at
      the University of Maryland Medical Center was reviewed. STUDY DESIGN AND METHODS:
      Patients undergoing therapeutic plasma exchange (TPE) for TMA from January 1,
      2000 through December 31, 2012 were reviewed. Those with known HIV-positive and 
      negative status were compared. RESULTS: Among 102 patients with known HIV status,
      28 (27%) were HIV-positive, including 3 with previously undiagnosed HIV. HIV
      positive patients had a median viral load of 89 500 copies/mL (range, 0->750 000
      copies/mL) and a median CD4 count of 58 cells/uL (range, 2-410 cells/uL).
      Compared to HIV-negative patients, HIV-positive patients more frequently
      presented with concurrent infections (60.7% vs. 23.7%; P = .0007), had a trend
      toward lower median platelet counts (3000/uL vs. 15 000/uL; P = .07) and more
      frequently had platelet counts less than 10 000/mcL (P = .02). Nevertheless,
      number of TPE procedures required for remission, remission rate, mortality, and
      relapse incidence were similar in HIV-positive and HIV-negative patients.
      CONCLUSIONS: The incidence described herein of HIV infection among TMA patients
      is the highest reported outside of South Africa. More severe thrombocytopenia in
      HIV-positive patients may reflect TMA in the setting of preexisting HIV
      associated thrombocytopenia. HIV should be considered in patients with TMA, and
      TMA should be considered in HIV-positive patients with severe thrombocytopenia.

PMID- 29377225
TI  - Pathogenic mechanisms of invasive group A Streptococcus infections by influenza
      virus-group A Streptococcus superinfection.
AB  - Group A Streptococcus (GAS) are pathogenic bacteria of the genus Streptococcus
      and cause severe invasive infections that comprise a wide range of diverse
      diseases, including acute respiratory distress syndrome, renal failure, toxic
      shock-like syndrome, sepsis, cellulitis and necrotizing fasciitis. The essential
      virulence, infected host and external environmental factors required for invasive
      GAS infections have not yet been determined. Superinfection with influenza virus
      and GAS induced invasive GAS infections was demonstrated by our team in a mouse
      model, after which clinical cases of invasive GAS infections secondary to
      influenza virus infection were reported by other investigators in Japan, USA,
      Canada, UK China, and other countries. However, the pathogenic mechanisms
      underlying influenza virus-GAS superinfection are not yet fully understood. The
      present review describes the current knowledge about invasive GAS infections by
      superinfection. Topics addressed include the bacteriological, virological and
      immunological mechanisms impacting invasion upon superinfection on top of
      underlying influenza virus infection by GAS and other bacteria (i.e.,
      Streptococcus pneumoniae and Staphylococcus aureus). Future prospects are also
      discussed.

PMID- 29377226
TI  - Prostaglandin-mediated recovery from bacteremia delays larval development in fall
      armyworm, Spodoptera frugiperda.
AB  - Insect immunity includes a surveillance system that detects and signals
      infections, coupled with hemocytic and humoral immune functions. These functions
      are signaled and coordinated by several biochemicals, including biogenic amines,
      insect cytokines, peptides, and prostaglandins (PGs). The actions of these
      mediators are coordinated within cells by various forms of cross-talk among the
      signaling systems and they result in effective reactions to infection. While this
      is well understood, we lack information on how immune-mediated recovery
      influences subsequent juvenile development in surviving insects. We investigated
      this point by posing the hypothesis that PG signaling is necessary for larval
      recovery, although the recovery imposes biological costs, registered in
      developmental delays and failures in surviving individuals. Here, we report that
      nodulation responses to infections by the bacterium, Serratia marcescens,
      increased over time up to 5 h postinfection, with no further nodulation; it
      increased in a linear manner with increasing bacterial dosages. Larval
      survivorship decreased with increasing bacterial doses. Treating larvae with the
      PG-biosynthesis inhibitor, indomethacin, led to sharply decreased nodulation
      reactions to infection, which were rescued in larvae cotreated with indomethacin
      and the PG-precursor, arachidonic acid. Although nodulation was fully rescued,
      all bacterial challenged larvae suffered reduced survivorship compared to
      controls. Bacterial infection led to reduced developmental rates in larvae, but
      not pupae. Adult emergence from pupae that developed from experimental larvae was
      also decreased. Taken together, our data potently bolster our hypothesis.

PMID- 29377227
TI  - Lymphoproliferative disorders in patients with chronic myeloproliferative
      neoplasms: A systematic review.
AB  - Patients with a Ph-negative myeloproliferative neoplasm (MPN) may harbor or
      develop lymphoproliferative disorders (LPD), however, the clinical and molecular
      determinants of MPN and LPD co-occurrence are still uncertain. To systematically
      pool the available knowledge, we conducted a scoping review of literature
      published since January 2005 and analyzed single-patient clinical data from 50
      papers reporting 214 individuals harboring both MPN and LPD. Patients had been
      diagnosed essential thrombocythemia (44%), polycythemia vera (29%), or
      myelofibrosis (23%) at a median age of 67 years (26-94): half of them incurred a
      LPD after a median of 72 months from MPN diagnosis, while in 20% the LPD
      diagnosis was antecedent or synchronous. Patients mainly incurred indolent LPD,
      particularly chronic lymphocytic leukemia (CLL), while aggressive lymphomas and
      multiple myeloma were a relevant portion of the LPDs occurring in the follow-up
      of MPN. CLL was preferentially diagnosed in PV patients and was associated with a
      very high male-to-female ratio, as well as an older age at MPN diagnosis. On
      converse, multiple myeloma was rarely reported in PV patients and was
      preferentially diagnosed in female patients not harboring the JAK2 V617F
      mutation. Based on the 46 cases reporting follow-up data, median survival after
      MPN diagnosis was 96 months. This thorough review of published evidence confirms
      that LPD are relevant clinical events in the history of MPN patients. Controlled
      studies are needed to better refine individuals at higher risk of developing LPD,
      to support surveillance programs and to avoid therapies possibly favoring LPD.

PMID- 29377229
TI  - microRNA-129-5p Involved in the Neuroprotective Effect of Dexmedetomidine on
      Hypoxic-Ischemic Brain Injury by Targeting COL3A1 through the Wnt/beta-Catenin
      Signaling Pathway in Neonatal Rats.
AB  - Our study aims to elucidate the mechanisms how microRNA-129-5p (miR-129-5p)
      involved in neuroprotective effect of dexmedetomidine (DEX) on hypoxic-ischemic
      brain injury (HIBI) by targeting COL3A1 through the Wnt/beta-catenin signaling
      pathway in neonatal rats. A total of 120 rats were obtained, among which 15 rats
      were selected as sham group and rest rats as model, DEX, DEX + negative control
      (DEX + NC), DEX + miR-129-5p mimics, DEX + miR-129-5p inhibitors, DEX + XAV-939
      and DEX + miR-129-5p inhibitors + XAV-939 groups. Dual-luciferase reporter assay
      was performed for the target relationship between miR-129-5p and COL3A1. Weight
      rate and water content of cerebral hemisphere were detected. qRT-PCR and Western
      blotting were conducted to detect miR-129-5p expression and expressions of
      COL3A1, E-cadherin, T-cell factor (TCF)-4, and beta-catenin. The DEX, DEX + miR
      129-5p mimics, DEX + XAV-939 groups had increased weight rate of cerebral
      hemisphere, but decreased water content of left cerebral hemisphere, levels of
      COL3A1, beta-catenin, TCF-4, and E-cadherin in hippocampus compared with the
      model and DEX + miR-129-5p inhibitors groups. COL3A1 was verified as the target
      gene of the miR-129-5p. Compared with the DEX + NC and DEX + miR-129-5p
      inhibitors + XAV-939 groups, the DEX + XAV-939 and DEX + miR-129-5p mimics groups
      had elevated weight rate of cerebral hemisphere, but reduced water content of
      left cerebral hemisphere, levels of COL3A1, beta-catenin, TCF-4, and E-cadherin
      in hippocampus. Our findings demonstrate that miR-129-5p improves the
      neuroprotective role of DEX in HIBI by targeting COL3A1 through the Wnt/beta
      catenin signaling pathway in neonatal rats. This article is protected by
      copyright. All rights reserved.

PMID- 29377228
TI  - Developmental pharmacogenetics of CYP2C19 in neonates and young infants:
      omeprazole as a probe drug.
AB  - AIMS: Although substantial progress has been made in understanding of ontogeny of
      drug metabolism, there is still a gap of knowledge in developmental
      pharmacogenetics in neonates. We hypothesized that both age and pharmacogenetics
      might explain the developmental pattern of CYP2C19. We conducted a population
      pharmacokinetic-pharmacogenetic study to quantify the developmental
      pharmacogenetics of CYP2C19 in neonates and young infants using omeprazole as a
      probe drug. METHODS: Pharmacokinetic samples were collected from 51 Caucasian
      neonates and young infants, who were receiving omeprazole treatment. Population
      pharmacokinetic-pharmacogenetic analysis of omeprazole and its metabolites was
      performed using NONMEM. RESULTS: Data fitted a one-compartment parent and
      metabolite model with first-order absorption and elimination. CYP2C19 and CYP3A4
      are predominantly involved in the metabolism of omeprazole despite their
      relatively low activities compared to adults. The clearance of omeprazole
      converted to 5-hydroxy-omeprazole (CLOMZ-M1 ) increases with postnatal age. In
      CYP2C19 poor and intermediate metabolizers, model-predicted CLOMZ-M1 are 12.5% (5
      95% percentile: 3-14.9%) and 44.9% (5-95% percentile: 29.9-72.6%) of the value in
      extensive/ultrarapid metabolizer, respectively. Model-predicted absorption rate
      constant of omeprazole is 6.93 (5-95% percentile: 3.01-14.61) times higher in
      ABCB1 homozygous mutant patients, 1.86 (5-95% percentile: 0.86-3.47) times higher
      in ABCB1 heterozygous patients than that in ABCB1 homozygous wild-type patients.
      CONCLUSIONS: Developmental pharmacogenetics of CYP2C19 was quantitatively
      described in neonates and young infants using omeprazole as a probe drug. Our
      findings emphasize the importance of semiphysiological developmental
      pharmacokinetic modelling approach when evaluating developmental pharmacogenetics
      of drugs with multiple routes of biotransformation.

PMID- 29377230
TI  - Intergenerational associations of the approximate number system in toddlers and
      their parents.
AB  - From birth, humans are able to discriminate quantities using the approximate
      number system (ANS). However, previous methods have only been suitable to examine
      ANS functioning in infancy and older children. The goals of this study were
      twofold: first, to modify an existing method of assessing ANS functioning for
      toddlerhood; and second, to investigate individual differences in toddlers' ANS
      performance by examining correlations with their parents' ANS acuity. Using a
      preferential looking paradigm, we found that 1- to 3-year-olds (N = 46) looked
      significantly longer to numerically changing images compared to numerically
      constant ones suggesting that the paradigm is a suitable measure of ANS
      functioning in toddlerhood. Furthermore, we found a positive relation between
      toddlers' ANS performance and that of their parents (assessed using a non
      symbolic number comparison task) independent of children's vocabulary or parents'
      perceived math ability or preference for math. These findings are consistent with
      a specific intergenerational transmission of the ANS. Statement of contribution
      What is already known on this subject? Past methods used to examine ANS
      functioning were only suitable for infants and older children. Little research
      has examined sources underlying individual difference in ANS acuity. What does
      this study add? We developed a preferential looking task to assess ANS
      functioning in toddlerhood. Individual differences in toddlers' ANS functioning
      are correlated with their parents' ANS acuity.

PMID- 29377231
TI  - Epidermotropic presentation by splenic B-cell lymphoma: The importance of
      clinical-pathologic correlation.
AB  - There are exceedingly rare reports of patients with epidermotropic B-cell
      lymphomas. A subset presented with intermittent, variably pruritic papular
      eruptions and involvement of their spleens, peripheral blood and bone marrow at
      the time of diagnosis. Furthermore, some experienced an indolent course despite
      dissemination of their lymphomas. We report a 66-year-old woman with a 12-year
      history of intermittent eruptions of non-pruritic, salmon-colored papules on her
      torso and proximal extremities that occurred in winter and resolved with outdoor
      activity in spring. Skin biopsy revealed an epidermotropic B-cell lymphoma with a
      non-specific B-cell phenotype and heavy chain class switching with IgG
      expression. On workup, our patient exhibited mild splenomegaly and low-level
      involvement of her peripheral blood and bone marrow by a kappa-restricted B-cell
      population. A splenic B-cell lymphoma was diagnosed. Considering her longstanding
      history and absences of cytopenias, our patient has been followed without
      splenectomy or systemic therapy. Furthermore, the papules have responded
      dramatically to narrowband UVB. Our case and a review of similar rare reports aim
      to raise awareness among dermatopathologists and dermatologists of a clinically
      distinct and indolent subset of epidermotropic splenic lymphomas with
      characteristic clinical and histologic findings.

PMID- 29377232
TI  - Subvalvular aortic stenosis: a review of current literature.
AB  - Subvalvular aortic stenosis (SAS) is one of the common adult congenital heart
      diseases, with a prevalence of 6.5%. It is usually diagnosed in the first decade
      of life. Echocardiography is the test of choice to diagnose SAS. Surgical
      correction is the best treatment modality, and the prognosis is usually
      excellent. In this review, we describe the pathophysiology, diagnosis, prognosis,
      and management of SAS with a focus on different pathophysiologic mechanisms,
      diagnostic approach, and prognosis of the disease by reviewing the current
      literature.

PMID- 29377233
TI  - Effects of overexpression and inhibited expression of thymosin, an actin
      interacting protein from Bombyx mori, on BmNPV proliferation and replication.
AB  - Previous study showed that exogenously applied recombinant thymosin from Bombyx
      mori (BmTHY) reduces B. mori nucleopolyhedrovirus (BmNPV) proliferation in
      silkworm. Which stands to reason that BmTHY in B. mori is crucial for the defense
      against BmNPV. However, little is known about the effect of endogenously
      overexpressed or repressed BmTHY on B. mori resistance to virus infection. To
      study this issue, we constructed an overexpression and inhibited expression
      systems of BmTHY in BmN cells. The viral titer and the analysis from the
      quantitative real-time polymerase chain reaction (PCR) revealed that
      overexpression of BmTHY decreased the copies of BmNPV gene gp41, which goes over
      to inhibit the proliferation of BmNPV in BmN cells, while the inhibited
      expression of BmTHY significantly enhanced viral proliferation in infected BmN
      cells. These results indicated that endogenous BmTHY can inhibit BmNPV
      proliferation and replication in infected BmN cells. Furthermore, Co-IP showed
      that BmTHY could bind to actin in BmN cells. Also, the overexpression or
      inhibited expression of BmTHY shifted the ratio of F/G-actin in infected BmN
      cells. Lastly, the BmTHY, an actin-interacting protein, might be one of the key
      host factors against BmNPV, which inhibits viral proliferation and replication in
      BmN cells.

PMID- 29377234
TI  - LncRNA SNHG1 regulates cerebrovascular pathologies as a competing endogenous RNA
      through HIF-1alpha/VEGF signaling in ischemic stroke.
AB  - Studies have shown that long noncoding ribonucleic acids (lncRNAs) play critical
      roles in multiple biologic processes. However, the Small Nucleolar RNA Host Gene
      1 (SNHG1) function and underlying molecular mechanisms in ischemic stroke have
      not yet been reported. In the present study, we found that SNHG1 expression was
      remarkably increased both in isolated cerebral micro-vessels of a middle cerebral
      artery occlusion (MCAO) mice model, and in oxygen-glucose deprivation (OGD)
      cultured mice brain micro-vascular endothelial cells (BMECs), meanwhile, the
      SNHG1 level was negatively correlated with miR-18a in MCAO mice. Mechanistically,
      SNHG1 inhibition presents larger brain infarct size and worsens neurological
      scores in MCAO mice. Consistent with the in vivo findings, SNHG1 inhibition also
      significantly increased caspase-3 activity and cell apoptosis in OGD-cultured
      BMECs. Furthermore, we found that SNHG1 functions as a competing endogenous RNA
      (ceRNA) for miR-18a, thereby regulating the de-repression of its endogenous
      target HIF-1alpha and promoting BMEC survival through HIF-1alpha/VEGF signaling.
      This study found a neuroprotective effect of SNHG1 mediated by HIF-1alpha/VEGF
      signaling through acting as a ceRNA for miR-18a. These findings reveal a novel
      function of SNHG1, which contributes to an extensive understanding of ischemic
      stroke and provides novel therapeutic options for this disease.

PMID- 29377235
TI  - Vedolizumab in patients with concurrent primary sclerosing cholangitis and
      inflammatory bowel disease does not improve liver biochemistry but is safe and
      effective for the bowel disease.
AB  - BACKGROUND: Blocking of lymphocyte trafficking to bile ducts is a potential
      mechanism to alter the disease course of patients with primary sclerosing
      cholangitis (PSC). AIM: To describe the effect of the alpha4 beta7 integrin
      antibody, vedolizumab, on liver biochemistry and disease activity in patients
      with PSC and inflammatory bowel disease (IBD). METHODS: This is a retrospective
      multi-centre study of adult patients with a diagnosis of both IBD and PSC. The
      primary outcome was change in serum alkaline phosphatase level at weeks 14 and
      30. Secondary outcomes included changes in other liver biochemistries and in
      clinical outcomes for the bowel disease. A safety analysis for adverse events was
      performed. RESULTS: Thirty-four patients (16 Crohn's disease, 18 ulcerative
      colitis) were included. Nine (26%) had a history of liver transplant. Median
      follow-up on vedolizumab was 9 months (IQR: 7-16). There was no overall change in
      serum alkaline phosphatase level with vedolizumab therapy (median 268 [IQR: 105
      551] IU/L at baseline versus 249 [IQR: 183-634] IU/L, P = 0.99 at week 30). No
      significant changes in other liver biochemistries or the Mayo PSC Risk Score were
      demonstrated at week 30. Clinical remission was achieved at week 30 in 55% of
      Crohn's disease and 29% of ulcerative colitis patients. Seven (21%) patients
      ceased vedolizumab; six patients stopped therapy due to persistent IBD activity
      and one for worsening of liver biochemistries. CONCLUSION: Vedolizumab treatment
      in patients with PSC and IBD did not improve liver biochemistry but was
      associated with improvement in bowel disease and a favourable safety profile.

PMID- 29377236
TI  - Are the health needs of young people with cerebral palsy met during transition
      from child to adult health care?
AB  - BACKGROUND: The transition from child to adult health care is a particular
      challenge for young people with cerebral palsy, who have a range of needs. The
      measurement of reported needs, and in particular unmet needs, is one means to
      assess the effectiveness of services. METHODS: We recruited 106 young people with
      cerebral palsy, before transfer from child services, along with their parents to
      a 3-year longitudinal study. Reported needs were measured with an 11-item
      questionnaire covering speech, mobility, positioning, equipment, pain, epilepsy,
      weight, control of movement, bone or joint problems, curvature of the back, and
      eyesight. Categorical principal component analysis was used to create factor
      scores for bivariate and regression analyses. RESULTS: A high level of reported
      needs was identified particularly for control of movement, mobility, and
      equipment, but these areas were generally being addressed by services. The
      highest areas of unmet needs were for management of pain, bone or joint problems,
      and speech. Analysis of unmet needs yielded two factor scores, daily living
      health care and medical care. Unmet needs in daily living health care were
      related to severity of motor impairment and to attending nonspecialist education.
      Unmet needs tended to increase over time but were not significantly (p > .05)
      related to whether the young person had transferred from child services.
      CONCLUSIONS: Reporting of unmet needs can indicate where service development is
      required, and we have shown that the approach to measurement can be improved. As
      the number of unmet health needs at the start of transition is considerable,
      unmet health needs after transition cannot all be attributed to poor transitional
      health care. The range and continuation of needs of young people with cerebral
      palsy argue for close liaison between adult services and child services and
      creation of models of practice to improve coordination.

PMID- 29377237
TI  - Drosophila melanogaster: A model to study obesity effects on genes expression and
      developmental changes on descendants.
AB  - Maternal obesity and metabolic diseases are two of the most important potential
      dangers to offspring, given that impaired offspring may cause deficiencies that
      impair the adult life and health. This study evaluated the oxidative damage, the
      enzymatic antioxidant defenses, and the enzymes of fatty acid metabolism, such as
      Acyl-CoA Synthetase and Acetyl-CoA Synthetase (mRNA expression levels), as well
      as the modulation of cell stress signaling pathway, as Hsp83, and gene expression
      and insulin-like peptide DILP6 in Drosophila melanogaster models that received a
      high fat diet (HFD) (10% and 20% of coconut oil) throughout their development
      period. After 7 days, the progenitor flies were removed and, the remaining eggs
      were monitored daily, until the eclosion. The descendants were then exposed to a
      regular diet (RD). The results revealed that the HFD caused a decrease in the
      proportion of eclosion, lifespan, MTT reduction in mitochondrial enriched
      fractions, AceCS1 levels, mRNA expression levels (SOD and CAT), and in catalase
      activity a decrease was only observed in the group that received the highest
      concentration of coconut oil. In parallel, it was demonstrated an increase in the
      upregulation of HSP83 mRNA levels, but only when 10% of coconut oil was added,
      and an increase in glucose and triglyceride levels, as well as in DILP6 mRNA
      levels in larger concentration of coconut oil tested (20%). In conclusion, flies
      that have progenitors fed with HFD can develop metabolic dysfunctions, causing
      oxidative insults, which are involved in the shortening of lifespan.

PMID- 29377238
TI  - Pretreatment of glial cell-derived neurotrophic factor and geranylgeranylacetone
      ameliorates brain injury in Parkinson's disease by its anti-apoptotic and anti
      oxidative property.
AB  - The aim of the present study was to determine the combined effects of glial cell
      derived neurotrophic factor (GDNF) and geranylgeranylacetone (GGA) on neuron
      apoptosis and oxidative stress in Parkinson's disease (PD). A mouse MPTP model of
      PD and cellular models of H2 O2 and MPP+ -treated PC12 cells were established.
      Swimming, pole, and traction tests were used to detect behavioral impairment.
      Tyrosine hydroxylase (TH) immunohistochemistry was used to evaluate the neuron
      loss. TUNEL and flow cytometer method were used to identify the neuron apoptosis.
      MDA levels and activities of antioxidant enzymes were used to detect the
      oxidative damage. The PD model of mice received GDNF and GGA exhibited a
      significant recovery in their swim, pole, and traction scores. Moreover, the
      combined treatment significantly reduced the neuron apoptosis in the substantia
      nigra (SN) of PD mice or in H2 O2 or MPP+ -induced PC12 cells compared with the
      single drug group. In addition, significant reduction of MDA levels and
      improvement of activities of CAT, SOD, and GSH-px were observed after GDNF and
      GGA treatment in the PD model and H2 O2 or MPP+ -induced PC12 cells. The
      combination of GDNF and GGA ameliorated neural apoptosis and oxidative damage in
      PD.

PMID- 29377239
TI  - Retraction: Liang, Y., Ma, Y., Li, L., Shen, X., Xin, T., Zhao, Y. and Ma, R.
      (2018), Effect of Long Non-Coding RNA LINC01116 on Biological Behaviors of Non
      Small Cell Lung Cancer Cells via the Hippo Signaling Pathway. J. Cell. Biochem.
      Accepted Author Manuscript. doi:10.1002/jcb.26711.
AB  - The above article from the Journal of Cellular Biochemistry, published online on
      27 January 2018 in Wiley Online Library as an Accepted Article, has been
      withdrawn by agreement between the authors, the journal Editor in Chief, Gary
      Stein and Wiley Periodicals, Inc. The withdrawal has been agreed due to
      determination by the authors that the data to support the therapeutic potential
      of LINC01116 in non-small cell lung cancer in vivo needs further study and
      analysis.

PMID- 29377240
TI  - The exosomes released from different cell types and their effects in wound
      healing.
AB  - Despite important advances in regenerative medicine and tissue engineering,
      still, wound healing remains a challenging clinical problem. Cell therapy has
      opened a new viewpoint in medicine as well as wound management, although it has
      some limitations. On the other hand, there are some hopes for the eliminated of
      cellular therapies limitations by "exosomes." The term "exosome" has been
      frequently used to describe all vesicles released by different cells into the
      extracellular environment and can influence tissue responses to injury,
      infection, immune system, and healing. Exosomes contain cytokines and growth
      factors, signaling lipids, mRNAs, and regulatory miRNAs that have been found in
      some body fluids and can be transferred between cells to mediating cell-to-cell
      communication and interactions. Recently, several studies have demonstrated that
      exosomes are one of the key secretory products of various cell type especially
      mesenchymal stem cells (MSCs) to regulate many biological processes such wound
      healing. Hence, understanding these exosomes effects may help to improve wound
      management and highlight a new therapeutic model for cell-free therapies with
      decreased side effects for the wound repair.

PMID- 29377241
TI  - The extracellular vesicles-derived from mesenchymal stromal cells: A new
      therapeutic option in regenerative medicine.
AB  - Mesenchymal stem cells (MSCs) are adult multipotent cells that due to their
      ability to homing to damaged tissues and differentiate into specialized cells,
      are remarkable cells in the field of regenerative medicine. It's suggested that
      the predominant mechanism of MSCs in tissue repair might be related to their
      paracrine activity. The utilization of MSCs for tissue repair is initially based
      on the differentiation ability of these cells; however now it has been revealed
      that only a small fraction of the transplanted MSCs actually fuse and survive in
      host tissues. Indeed, MSCs supply the microenvironment with the secretion of
      soluble trophic factors, survival signals and the release of extracellular
      vesicles (EVs) such as exosome. Also, the paracrine activity of EVs could mediate
      the cellular communication to induce cell-differentiation/self-renewal. Recent
      findings suggest that EVs released by MSCs may also be critical in the
      physiological function of these cells. This review provides an overview of MSC
      derived extracellular vesicles as a hopeful opportunity to advance novel cell
      free therapy strategies that might prevail over the obstacles and risks
      associated with the use of native or engineered stem cells. EVs are very stable;
      they can pass the biological barriers without rejection and can shuttle bioactive
      molecules from one cell to another, causing the exchange of genetic information
      and reprogramming of the recipient cells. Moreover, extracellular vesicles may
      provide therapeutic cargo for a wide range of diseases and cancer therapy.

PMID- 29377243
TI  - Clinical and endoscopic evaluations of sessile serrated adenoma/polyps with
      cytological dysplasia.
AB  - BACKGROUND AND AIM: Although sessile serrated adenoma/polyps (SSA/Ps) are
      considered to be premalignant lesions and rapidly progress to carcinomas after
      they develop cytological dysplasia (CD), a treatment strategy for SSA/Ps in Asian
      countries is still being debated and has not yet been established. The present
      study aimed to propose a treatment strategy for SSA/Ps. METHODS:
      Histopathological data of patients, who underwent colonoscopy at our center
      between January 2011 and December 2016, were reviewed. Data of patients with >= 1
      SSA/P were retrieved, and clinicopathological characteristics were
      retrospectively analyzed. RESULTS: A total of 281 patients with 326 SSA/Ps,
      including 258 patients who had 300 SSA/Ps without CD (SSA/Ps-CD[-]) and 23
      patients who had 26 SSA/Ps with CD (SSA/Ps-CD[+]), were evaluated in this study.
      Although SSA/Ps-CD(+) were often found in older female patients and in the
      proximal colon, there were no significant differences between SSA/Ps-CD(-) and
      SSA/Ps-CD(+). Endoscopic morphological findings, such as large or small nodules
      on the surface and partial protrusion of the lesions, were significantly more
      common in SSA/Ps-CD(+) than in SSA/Ps-CD(-). Although the diagnostic ability of
      nodule/protrusion in lesions to predict CD within SSA/Ps was very high with an
      accuracy of 93.9% and a negative predictive value of 95.4%, sensitivity was low
      at 46.2%. SSA/Ps-CD(+) were significantly larger than SSA/Ps-CD(-), and the rate
      of CD within SSA/Ps significantly increased with lesion size (<= 5 mm, 0%; 6-9
      mm, 6.0%; >= 10 mm, 13.6%). CONCLUSION: The study proposes removing all SSA/Ps >=
      6 mm in order to remove high-risk SSA/Ps-CD(+), with high sensitivity.

PMID- 29377244
TI  - MicroRNA-132 attenuates LPS-induced inflammatory injury by targeting TRAF6 in
      neuronal cell line HT-22.
AB  - Epilepsy is a common neurological disorder in the central nervous system.
      Inflammation disrupts the blood-brain barrier (BBB), which is responsible for
      maintaining brain homeostasis. This study was aimed to investigate the functional
      role of microRNA (miR)-132 in hippocampal HT-22 cells under lipopolysaccharide
      (LPS) stimulation. In vitro cell inflammatory model was constructed by LPS
      stimulation. Inflammatory cell injury was evaluated according to the alterations
      of cell viability, apoptosis, and expression of inflammatory cytokines. Then, miR
      132 level after LPS treatment was assessed. Subsequently, miR-132 was abnormally
      expressed after cell transfection, and the effects of miR-132 on LPS-induced cell
      inflammatory injury as well as phosphorylated levels of key kinases in the NF
      kappaB and MAPK kinase (MEK)/ERK pathways were determined. The target gene of miR
      132 was virtually screened and verified, and whether miR-132 affected HT-22 cells
      under LPS stimulation through regulating the target gene was verified. The
      results showed that the level of miR-132 was down-regulated by LPS in HT-22
      cells, and the LPS-induced inflammatory injury could be reduced by miR-132
      overexpression. Then, the phosphorylated levels of kinases in the NF-kappaB and
      MEK/ERK pathways were decreased by miR-132 overexpression. Tumor necrosis factor
      receptor-associated factor 6 (TRAF6) was predicted and verified to be a target of
      miR-132. Moreover, the alterations induced by miR-132 overexpression in the LPS
      treated HT-22 cells were abrogated by TRAF6 overexpression. Therefore, we drew
      the conclusion that LPS down-regulated miR-132 and miR-132 attenuated LPS-induced
      inflammatory cell injury by targeting TRAF6, along with the inhibition of the NF
      kappaB and MEK/ERK pathways.

PMID- 29377242
TI  - An update on cell intrinsic negative regulators of the NLRP3 inflammasome.
AB  - Inflammasomes are multimeric protein complexes that promote inflammation (through
      specific cleavage and production of bioactive IL-1beta and IL-18) and pyroptotic
      cell death. The central role of inflammasomes in combating infection and
      maintaining homeostasis has been studied extensively. Although inflammasome
      mediated inflammation and cell death are vital to limit pathogenic insults and to
      promote wound healing/tissue regeneration, unchecked/uncontrolled inflammation,
      and cell death can cause cytokine storm, tissue damage, autoinflammatory and
      autoimmune diseases, and even death in the afflicted individuals. NLRP3 is one of
      the major cytosolic sensors that assemble an inflammasome. Given the adverse
      consequences of uncontrolled inflammasome activation, our immune system has
      developed tiered mechanisms to inhibit NLRP3 inflammasome activation. In this
      review, we highlight and discuss recent advances and our current understanding of
      mechanisms by which NLRP3 inflammasome can be negatively regulated.

PMID- 29377245
TI  - Hepatitis C virus re-treatment in the era of direct-acting antivirals:
      projections in the USA.
AB  - BACKGROUND: The introduction of oral direct-acting antivirals (DAAs) has
      dramatically changed the landscape of HCV treatment. However, a small percentage
      of patients fail to achieve sustained virologic response (SVR). Understanding the
      number of people who fail on DAAs and require re-treatment is important for
      budget impact and disease burden projections. AIM: To quantify the number of HCV
      patients who fail to achieve SVR on oral DAAs (NS5A vs. non-NS5A) and require re
      treatment. METHODS: We used a mathematical model to simulate clinical management
      of HCV in the USA, which included the implementation of HCV screening, treatment,
      and disease progression. We simulated different waves of DAA treatment and used
      real-world data to extract SVR rates and market shares of available therapies.
      RESULTS: Our model projected that the number of people living without viraemia
      (i.e. cured) would increase from 0.70 million in 2014 to 1.78 million by 2020.
      Between 2014 and 2020, 1.50 million people would receive treatment with DAAs, of
      whom 124 000 (8.3%) are projected to fail to achieve SVR. Among those treatment
      failures, 66 600 (53.7%) patients would fail treatment with NS5A inhibitors and
      69 600 (56.1%) would have cirrhosis. During the same period, 34 200 people would
      progress to decompensated cirrhosis and 27 300 would develop hepatocellular
      carcinoma after failing to achieve SVR. CONCLUSIONS: Even in the era of highly
      effective DAAs, a significant number of patients will fail to achieve SVR and
      will require re-treatment options. Timely and effective re-treatment is essential
      to prevent the long-term sequelae of HCV.

PMID- 29377246
TI  - Searching for human oncoviruses: Histories, challenges, and opportunities.
AB  - Oncoviruses contribute significantly to cancer burden. A century of tumor
      virological studies have led to the discovery of seven well-accepted human
      oncoviruses, cumulatively responsible for approximately 15% of human cancer
      cases. Virus-caused cancers are largely preventable through vaccination.
      Identifying additional oncoviruses and virus-caused tumors will advance cancer
      prevention and precision medicine, benefiting affected individuals, and society
      as a whole. The historic success of finding human oncoviruses has provided a
      unique lesson for directing new research efforts in the post-sequencing era.
      Combing the experiences from these pioneer studies with emerging high-throughput
      techniques will certainly accelerate new discovery and advance our knowledge of
      the remaining human oncoviruses.

PMID- 29377247
TI  - Preanalytical validation of an in-house radioimmunoassay for measuring
      calprotectin in feline specimens.
AB  - BACKGROUND: Calprotectin is a marker of inflammatory disorders in people, and
      serum and fecal calprotectin were shown to be increased in dogs with
      gastrointestinal inflammation. Biomarkers of gastrointestinal inflammation are
      currently lacking in cats. OBJECTIVES: The purpose of the study was to
      analytically validate the canine calprotectin radioimmunoassay for quantification
      of calprotectin in feline specimens. METHODS: The immunoassay was analytically
      validated by determining assay working range, dilutional parallelism, spiking
      recovery, and intra- and inter-assay variability. Reference intervals for fecal
      calprotectin were established from healthy cats, and the influence of age, sex,
      and housing condition on fecal calprotectin was determined. RESULTS: The working
      range of the assay was 1.5-346.2 MUg/g of feces and 11.2-8654.4 MUg/L of serum.
      Observed-to-expected ratios (O/E) for serial dilutions of fecal extracts ranged
      from 77.3% to 112.0% (mean: 99.2%) and from 95.7% to 161.4% (mean: 118.5%) for
      spiking recovery. Intra- and inter-assay coefficients of variation for fecal
      samples were <= 11.0% and <= 12.8%, respectively. Fecal calprotectin
      concentrations ranged 1.5-66.5 MUg/g (3-day sample mean) and 1.5-126.1 MUg/g (3
      day sample maximum). Housing conditions, sex, or age did not affect fecal
      calprotectin (all P > .05). For serial dilutions of serum samples, O/E ranged
      from 96.0% to 152.0% (mean: 115.7%). Serum calprotectin concentrations in healthy
      cats ranged from 108.8 to 255.3 MUg/L (median: 158.2 MUg/L). CONCLUSIONS: The
      canine radioimmunoassay for the measurement of calprotectin is analytically
      sensitive, linear, reproducible, accurate, and sufficiently precise (CVA  <=
      43.2%) for use with feline feces (with a loss of accuracy at high calprotectin
      concentrations). The RIs for feline fecal calprotectin are comparable to those
      established for dogs. Independence of fecal calprotectin from age and sex agrees
      with findings in dogs.

PMID- 29377248
TI  - Characterization of estrous cycles and pregnancy in Somali wild asses (Equus
      africanus somaliensis) through fecal hormone analyses.
AB  - Although reproduction in the domestic horse has been well described, less is
      known about reproduction in wild equids. This study describes endocrine patterns
      associated with estrous cycles and pregnancy for Somali wild asses (Equus
      africanus somaliensis), an endangered African equid. Fecal samples were collected
      three times per week for more than 2 years from five female Somali wild asses at
      the Saint Louis Zoo; progestagen and estrogen metabolites were quantified using
      commercially available immunoassays. Progestagen analysis indicated that cycle
      lengths were 27.2 +/- 1.2 days and females cycled throughout the year.
      Progestagen levels during early pregnancy were low and not sustained above
      baseline until approximately 40 weeks prior to partition. Concentrations
      increased markedly around 16 weeks prior to delivery and peaked 2-3 weeks before
      birth. Fecal estrogen levels also increased significantly starting 40-45 weeks
      before parturition and reached their maximal value approximately 20 weeks prior
      to birth. Neither foal heat nor lactational suppression of estrus was observed,
      and females cycled within 45 days after delivery. These data are the first to
      describe the reproductive physiology of Somali wild asses. As the species faces
      increasing threats in the wild, this information may support conservation efforts
      by assisting with ex situ breeding programs.

PMID- 29377249
TI  - HMGB1-induced inflammatory response promotes bone healing in murine tooth
      extraction socket.
AB  - High mobility group box 1 (HMGB1) is a non-histone DNA-binding protein that is
      secreted into the extracellular milieu in response to inflammatory stimuli. The
      secreted HMGB1 has been suggested to mediate various inflammatory diseases.
      However, it is still unknown whether HMGB1 is involved in a healing process in
      the tooth extraction socket, the tissue containing gingival epithelium, and
      alveolar bone that is exposed to oral bacteria. In this study, we constructed a
      murine tooth extraction model with anti-HMGB1 neutralization antibody
      administration and observed the inflammatory response and bone healing process in
      tooth extraction sockets by molecular imaging of myeloperoxidase (MPO) activity,
      histological analysis, and quantitative RT-PCR. The translocation of HMGB1 from
      the nucleus to the cytoplasm in gingival epithelial cells and inflammatory cells
      was inhibited by anti-HMGB1 antibody administration. The MPO activity around the
      tooth extraction socket was significantly reduced, and the numbers of CD31- and
      CD68-positive cells were significantly lower in the anti-HMGB1 antibody treatment
      samples than in the control samples. The TRAP-positive cells, osteocalcin
      positive cells, and the neoplastic bone area were significantly lower in anti
      HMGB1 antibody treatment samples than in control samples. The expression levels
      of IL-1beta and VEGF-A were also decreased in anti-HMGB1 antibody treatment
      samples compared to that in control samples. Secreted HMGB1 induced initial acute
      inflammation and inflammatory cells recruitment after tooth extraction. HMGB1 was
      associated with angiogenesis and bone remodeling by osteoclast and osteoblast
      activation and promoted bone healing in the tooth extraction socket.

PMID- 29377250
TI  - Prediction of hepatic encephalopathy: Why disregard well-known risk factors?

PMID- 29377251
TI  - Relationships between Dicer 1 polymorphism and expression levels in the
      etiopathogenesis of preeclampsia.
AB  - Preeclampsia (PE) is a pregnancy-specific complication which is a major cause of
      maternal and fetal morbidity and mortality. Recent studies have shown the
      aberrant expression of microRNAs (miRNAs) in the placenta of patients with PE.
      Dicer1 is a key enzyme in the generation of small noncoding RNAs including
      miRNAs. The aim of this study is to investigate the relationship between maternal
      and placental Dicer1 rs3742330 polymorphism and placental Dicer1 mRNA expression
      in PE and normotensive pregnant women. The blood and placenta of PE pregnant and
      normotensive pregnant women were collected after delivery. Dicer1 rs3742330
      polymorphism was genotyped using PCR-RFLP method. The mRNA expression levels were
      measured using quantitative real time PCR. The maternal Dicer1 rs3742330
      polymorphism was not associated with PE or PE severity; however, the placental
      Dicer1 rs3742330 AG genotype was associated with two fold higher risk of PE and
      three fold higher risk of severe PE (P = 0.018 and P = 0.005, respectively). The
      relative mRNA expression of Dicer1 gene in the placenta did not differ between
      the two groups. In addition, the relative mRNA expression of Dicer1 gene was
      significantly lower in the placenta of women with rs3742330 AG+GG genotypes in
      the total population (P = 0.028) and PE women (P = 0.004), but not in the control
      group. In conclusion, there was a relationship between placental but not maternal
      Dicer1 rs3742330 polymorphism and PE. There was no difference in Dicer1 mRNA
      expression between the PE and control groups; however, it was significantly lower
      in the placenta of women with rs3742330 AG+GG genotypes.

PMID- 29377252
TI  - Hmox1 promotes osteogenic differentiation at the expense of reduced adipogenic
      differentiation induced by BMP9 in C3H10T1/2 cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate
      into a variety of cell types under proper stimuli. Bone morphogenetic protein 9
      (BMP9) is able to simultaneously induce both adipogenic and osteogenic
      differentiation of MSCs although the regulatory molecules involved remain to be
      fully identified and characterized. Heme oxygenase 1 (Hmox1) plays an essential
      role not only in fat metabolism, but also in bone development. In the present
      study, we investigated the functional role of Hmox1 in BMP9-induced
      osteogenic/adipogenic differentiation in MSCs line C3H10T1/2 and probed the
      possible mechanism involved. We found that BMP9 promoted the endogenous
      expression of Hmox1 in C3H10T1/2 cells. Overexpression of Hmox1 or cobalt
      protoporphyrin (CoPP), an inducer of Hmox1, increased BMP9-induced osteogenic
      differentiation in vitro. Subcutaneous stem cell implantation in nude mice
      further confirmed that Hmox1 potentiated BMP9-induced ectopic bone formation in
      vivo. In contrast, Hmox1 reduced BMP9-induced adipogenic differentiation in
      C3H10T1/2 cells. Although had no obvious effect on BMP9-induced Smad1/5/8
      phosphorylation, Hmox1 enhanced phosphorylation of p38, and AKT, while decreased
      phosphorylation of ERK1/2. Furthermore, Hmox1 increased total beta-catenin
      protein level, and promoted the nuclear translocation of beta-catenin in
      C3H10T1/2 cells. Taken together, our study strongly suggests that Hmox1 is likely
      to potentiate osteogenic differentiation and yet decrease adipogenic
      differentiation induced by BMP9 possibly through regulation of multiple signaling
      pathways.

PMID- 29377253
TI  - How to Explore Fetal Sacral Agenesis Without Open Dysraphism: Key Prenatal
      Imaging and Clinical Implications.
AB  - The estimated prevalence of fetal caudal dysgenesis is 1 per 100,000 births. The
      functional prognosis of sacral agenesis is dominated by the large spectrum of
      associated caudal malformations. Except for cases associated with hydrocephalus
      secondary to open spinal dysraphism or chromosomal anomalies, association with
      mental deficiency is rare. We propose a systematic prenatal approach to cases of
      fetal sacral agenesis based on 9 etiologic items: clinical context, type of
      sacral dysgenesis, associated spinal cord malformations, mobility of lower limbs,
      investigation of the presacral region, analysis of the gastrointestinal tract,
      analysis of the genitourinary tract, associated vertebral defects, and
      cytogenetic analysis.

PMID- 29377254
TI  - Glycosylated CD147 reduces myocardial collagen cross-linking in cardiac
      hypertrophy.
AB  - The mechanism of transition from chronic pressure overload-induced cardiac
      hypertrophy to heart failure is still unclear. Angiotensin II (Ang II) may be an
      important factor that mediates the transition in the end-stage of cardiac
      hypertrophy. In the present study, Goldblatt two-kidney one-clip (2K1C) rat model
      was used to simulate Ang II-induced hypertension. The elevated Ang II not only
      induced the concentric hypertrophy of left ventricle and cardiac fibrosis, but
      also increased the expression and glycosylation of CD147 in 2K1C rats. The left
      ventricular structure and function detected by echocardiogram showed a sign of
      the transition from cardiac hypertrophy to heart failure in 16 weeks of 2K1C
      rats. Ang II can activate N-acetylglucosamine transferase V (GnT-V), a key enzyme
      for CD147 glycosylation. Retinoic acid, an agonist of GnT-V, further increased
      glycosylated CD147, and activated matrix metalloproteinase-2/-9 (MMP-2 and MMP-9)
      in the hypertrophied left ventricle of 2K1C rat. Meanwhile, collagen cross
      linking in the hypertrophied left ventricle significantly reduced in 2K1C rats.
      On the contrary, tunicamycin, an inhibitor of N-glycan biosynthesis, inhibited
      glycosylation of CD147 and activity of MMP-2 and MMP-9, and then maintained a
      stable of collagen cross-linking in the 2K1C rat hearts. The above results
      suggested that Ang II increased glycosylated CD147 which activated MMP-2 and MMP
      9. Collagens were degraded by the activated MMPs and then reduced collagen cross
      linking. Finally, the hypertrophied left ventricle was progressively dilated in
      chronic pressure overload due to losing the limitation of collagen cross-linking.
      Therefore, the compensated hypertrophy of left ventricle gradually transited to
      congestive heart failure.

PMID- 29377255
TI  - Agmatine co-treatment attenuates allodynia and structural abnormalities in
      cisplatin-induced neuropathy in rats.
AB  - Cisplatin is a widely used antineoplastic agent in the treatment of various
      cancers. Peripheral neuropathy is a well-known side effect of cisplatin and has
      potential to result in limiting and/or reducing the dose, decreasing the quality
      of life. Thus, effective treatments are needed. Agmatine is an endogenous
      neuromodulator that has been shown to exert antiallodynic effects in various
      animal studies. The first aim of this study was to investigate the in vitro
      effects of agmatine on cisplatin-induced neurotoxicity. Primary cultures of
      dorsal root ganglia (DRG) which are the primary target of drug injury were
      prepared. DRG cells were incubated with cisplatin (100, 200, 500 MUm). Then,
      agmatine (10, 100, 500 MUm) was administered with the submaximal concentration of
      cisplatin. Cisplatin caused concentration-dependent neurotoxicity, and agmatine
      did not alter this effect. The second aim was to investigate the effects of
      agmatine on cisplatin-induced peripheral neuropathy in rats and the influence of
      nitric oxide synthase (NOS) inhibitor, L-NAME, in this effect. Female Sprague
      Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg),
      cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L-NAME (10 mg/kg) once a
      week for 5 weeks. The mechanical allodynia, hot plate, and tail clip tests were
      performed, and DRG cells and sciatic nerves were analyzed. Agmatine and
      agmatine+L-NAME combination attenuated CIS-induced mechanical allodynia and
      degeneration in DRG cells and sciatic nerves. However, L-NAME did not potentiate
      the antiallodynic or neuroprotective effect of agmatine. These findings indicate
      that agmatine co-administration ameliorates cisplatin-induced neuropathy and may
      be a therapeutic alternative.

PMID- 29377256
TI  - Expression pattern of PD-L1 and PD-L2 in classical Hodgkin lymphoma, primary
      mediastinal large B-cell lymphoma, and gray zone lymphoma.
AB  - OBJECTIVES: We aimed at investigating the relationship between classical Hodgkin
      lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBL), and gray zone
      lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the
      perspective of the aberration in programed cell death 1 and the programed death
      ligands (PDLs) network. METHODS: We explored the expression levels of PDLs and
      chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with
      GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization
      (FISH). RESULTS: Twenty-one cHL (62%), 3 PMBL (15%), and 6 GZL (46%) cases showed
      staining to PD-L1 antibodies in more than 70% of tumor cells. Two cHL (6%), 10
      PMBL (50%), and 3 GZL (23%) cases were not stained by PD-L1 antibodies. Patients
      over 40 years old manifest more frequent expression of PD-L1 in cHL. Proportion
      of tumors stained by PD-L2 antibody was increased in PMBL. FISH analyses with a
      PD-L1/PD-L2 probe detected 5 amplification, 1 gain, and 7 polysomy cases in cHL,
      1 amplification and 1 polysomy case in GZL, and amplification in 1 PMBL case.
      CONCLUSION: We identified increased staining of PD-L1 in cHL and that of PD-L2 in
      PMBL. GZL had a pattern similar to that of cHL.

PMID- 29377257
TI  - Exposure-response characterization of tofacitinib efficacy in moderate to severe
      ulcerative colitis: Results from a dose-ranging phase 2 trial.
AB  - AIMS: Tofacitinib is an oral, small molecule JAK inhibitor being investigated for
      ulcerative colitis (UC). In a phase 2 dose-ranging study, tofacitinib
      demonstrated efficacy vs. placebo as UC induction therapy. In this posthoc
      analysis, we aimed to compare tofacitinib dose and plasma concentration as
      predictors of efficacy and identify covariates that determined efficacy in
      patients with UC. METHODS: One- and two-compartment pharmacokinetic models, with
      first-order absorption and elimination, were evaluated to describe plasma
      tofacitinib concentration-time data at baseline and week 8. Relationships between
      tofacitinib exposure (dose, average plasma drug concentration during a dosing
      interval at steady state [Cav,ss ] and trough plasma concentration at steady
      state [Ctrough,ss ]) and week 8 efficacy endpoints were characterized using
      logistic regression analysis. Baseline disease, demographics, prior and
      concurrent UC treatment were evaluated as covariates. RESULTS: Plasma tofacitinib
      concentrations increased proportionately with dose and estimated oral clearance,
      and Cav,ss values were not significantly different between baseline and week 8.
      Dose, Cav,ss and Ctrough,ss performed similarly as predictors of efficacy based
      on statistical criteria for model fit and comparison of model predictions for
      each endpoint. Individual Cav,ss values were similar between clinical remitters
      and nonremitters at predicted efficacious doses (10 and 15 mg twice daily).
      Baseline Mayo score was a significant determinant of efficacy. Predicted
      differences from placebo in clinical remission at 10 mg twice daily for patients
      with baseline Mayo score >8 and <=8 were 39% (95% CI: 7-70) and 21% (-2-50),
      respectively. CONCLUSIONS: Exposure-response characterization demonstrated the
      potential of tofacitinib 10 and 15 mg twice daily as induction therapy for UC
      without monitoring of plasma drug concentrations for dose optimization.

PMID- 29377259
TI  - A quantitative comparison between SOX10 and MART-1 immunostaining to detect
      melanocytic hyperplasia in chronically sun-damaged skin.
AB  - Histologic differentiation of melanoma in situ (MIS) from solar keratosis on
      chronically sun-damaged skin is challenging. The first-line immunostain is
      usually MART-1/Melan-A, which can exaggerate the epidermal melanocytes, causing a
      diagnostic pitfall for MIS. By comparing MART-1 and SOX10 immunostaining, we
      scored the percentage of epidermal melanocytes per 2-mm diameter fields in
      pigmented actinic keratosis (n = 16), lichenoid keratosis (n = 7), junctional
      melanocytic nevus (n = 6), keratosis with atypical melanocytic proliferation (n =
      17) and MIS (n = 10). These cases represented an older population (68 years
      median age) and the head and neck (50%) was the most common anatomic site. MART-1
      score was significantly higher than SOX10 (P value <.05) in solar keratoses, but
      showed no difference in detecting melanocytic proliferations, demonstrating their
      equal detection rate of melanocytes. The sensitivity of both MART-1 and SOX10 was
      100%, while their specificities were 17% and 96%, respectively. These results
      show that SOX10 is more specific than MART-1 in distinguishing epidermal
      melanocytes on sun-damaged skin by avoiding overdiagnosis of melanoma.

PMID- 29377258
TI  - Transfer from paediatric to adult care for young adults with Type 2 diabetes: the
      SEARCH for Diabetes in Youth Study.
AB  - AIM: To describe factors associated with transfer from paediatric to adult care
      and poor glycaemic control among young adults with Type 2 diabetes, using the
      SEARCH for Diabetes in Youth study. METHODS: Young adults with Type 2 diabetes
      were included if they had a baseline SEARCH visit while in paediatric care at <
      18 years and >= 1 follow-up SEARCH visit thereafter at 18-25 years. At each
      visit, HbA1c , BMI, self-reported demographic and healthcare provider data were
      collected. Associations of demographic factors with transfer of care and poor
      glycaemic control (HbA1c >= 75 mmol/mol; 9.0%) were explored with multivariable
      logistic regression. RESULTS: 182 young adults with Type 2 diabetes (36% male,
      75% minority, 87% with obesity) were included. Most (n = 102, 56%) reported
      transfer to adult care at follow-up; a substantial proportion (n = 28, 15%)
      reported no care and 29% did not transfer. Duration of diabetes [odds ratio (OR)
      1.4, 95% confidence interval (95% CI) 1.1, 1.8] and age at diagnosis (OR 1.8, 95%
      CI 1.4, 2.4) predicted leaving paediatric care. Transfer to adult or no care was
      associated with a higher likelihood of poor glycaemic control at follow-up
      (adult: OR 4.5, 95% CI 1.8, 11.2; none: OR 4.6, 95% CI 1.4, 14.6), independent of
      sex, age, race/ethnicity or baseline HbA1c level. CONCLUSIONS: Young adults with
      Type 2 diabetes exhibit worsening glycaemic control and loss to follow-up during
      the transfer from paediatric to adult care. Our study highlights the need for
      development of tailored clinical programmes and healthcare system policies to
      support the growing population of young adults with youth-onset Type 2 diabetes.

PMID- 29377260
TI  - Nationwide survey on the use of horse antithymocyte globulins (ATGAM) in patients
      with acquired aplastic anemia: A report on behalf of the French Reference Center
      for Aplastic Anemia.
AB  - Antithymocyte globulins (ATG) plus cyclosporine (CSA) is the gold standard
      immunosuppressive treatment (IST) for patients with aplastic anemia. A
      prospective randomized trial showed in 2011 that hATG was superior to rabbit ATG
      for first-line treatment of severe AA. The French Health Agency (ANSM) permitted
      a patient-named authorization for temporary use (ATU) program of hATG (ATGAM,
      Pfizer) in patients with AA in 2011 since commercial access to hATG is not
      approved. We took advantage of this program to analyze the outcomes of 465
      patients who received antithymocyte globulins (ATGAM) plus CSA as first line
      treatment (n = 379; 81.5%), or for refractory (n = 26) or relapsed disease (n =
      33), from September 2011 to March 2017. In the entire cohort one year, 72% of the
      patients had partial and 13% had complete response, with worse response for
      patients with severe AA and a longer interval between diagnosis and IST (more
      than 6 months). Severe adverse events were mainly linked to infections (24%),
      hemorrhages (6%), and elevated liver function tests (5%). Overall at 12 months,
      9.7% of patients required second line IST and 15.6% received transplantation.
      Fifty-five patients died during the study mainly because of infections (53%).
      Factors predicting independently worse survival were age over 40 years,
      neutrophils less than 0.5 * 109 /L, male gender and longer delay between
      diagnosis and hATG (>6 months period). This study does illustrate the results of
      ATGAM with CSA in a true-life perspective and confirms ATGAM as standard of care
      IST to treat patients with AA not eligible for HSCT.

PMID- 29377262
TI  - A selection of abstracts presented at the 43rd annual conference of the
      anatomical society of Southern Africa (ASSA), 9-13 May 2015, Khaya iBHUBESI
      Conference Venue, Parys, Free State, South Africa.

PMID- 29377261
TI  - Quantum DNA Sequencing: A Peek Into a Dystopic Future?

PMID- 29377263
TI  - The alpha1-adrenergic receptor is involved in hepcidin upregulation induced by
      adrenaline and norepinephrine via the STAT3 pathway.
AB  - Elevated body iron stores are associated with hypertension progression, while
      hypertension is associated with elevated plasma catecholamine levels in patients.
      However, there is a gap in our understanding of the connection between
      catecholamines and iron regulation. Hepcidin is a key iron-regulatory hormone,
      which maintains body iron balance. In the present study, we investigated the
      effects of adrenaline (AD) and norepinephrine (NE) on hepatic hepcidin
      regulation. Mice were treated with AD, NE, phenylephrine (PE, alpha1-adrenergic
      receptor agonist), prazosin (PZ, alpha1-adrenergic receptor antagonist), and/or
      propranolol (Pro, beta-adrenergic receptor antagonist). The levels of hepcidin,
      as well as signal transducer and activator of transcription 3 (STAT3),
      ferroportin 1 (FPN1), and ferritin-light (Ft-L) protein in the liver or spleen,
      were assessed. Six hours after AD, NE, or PE treatment, hepatic hepcidin mRNA
      levels increased. Pretreatment with PZ, but not Pro, abolished the effects of AD
      or NE on STAT3 phosphorylation and hepatic hepcidin expression. When mice were
      treated with AD or NE continuously for 7 days, an increase in hepatic hepcidin
      mRNA levels and serum hepcidin concentration was also observed. Meanwhile, the
      expected downstream effects of elevated hepcidin, namely decreased FPN1
      expression and increased Ft-L protein and non-heme iron concentrations in the
      spleen, were observed after the continuous AD or NE treatments. Taken together,
      we found that AD or NE increase hepatic hepcidin expression via the alpha1
      adrenergic receptor and STAT3 pathways in mice. The elevated hepatic hepcidin
      decreased FPN1 levels in the spleen, likely causing the increased iron
      accumulation in the spleen.

PMID- 29377264
TI  - Understanding fibrosis in eosinophilic esophagitis: Are we there yet?
AB  - Eosinophilic esophagitis (EoE) is an immune/antigen-mediated, progressive
      fibrostenotic disease characterized by symptoms of esophageal dysfunction and
      abnormal eosinophilic infiltration in the esophagus. Despite current treatment
      modalities of dietary antigen elimination or topical corticosteroids, a subset of
      patients do not have clinical or histologic response. Even with resolution of
      superficial epithelial eosinophilia, patients may still have progressive
      subepithelial fibrosis, which may lead to esophageal strictures over time.
      Histologic identification of subepithelial fibrosis requires deep esophageal
      biopsies, which are not routinely obtained. Herein, we review the challenges in
      diagnosing and treating fibrosis in EoE. We propose the novel concept of vitamin
      D supplementation to treat fibrosis in EoE through downregulation of profibrotic
      mediator, transforming growth factor-beta.

PMID- 29377265
TI  - Watch-and-wait policy versus rituximab-combined chemotherapy in Japanese patients
      with intestinal follicular lymphoma.
AB  - BACKGROUND AND AIM: Few reports have demonstrated the effectiveness of treatments
      for intestinal follicular lymphoma (FL) because of the limited number of patients
      who undergo comprehensive small intestinal examinations. This study compared the
      efficacy of rituximab-combined chemotherapy in patients with asymptomatic and low
      tumor burden (LTB) intestinal FL, according to the criteria of the Groupe d'Etude
      des Lymphomes Folliculaires, with that of a "watch and wait" (W&W) approach.
      METHODS: The endoscopic examination for entire gastrointestinal tracts was
      performed in 29 Japanese patients with intestinal FL. These patients had CD21
      positive follicular dendritic cells arranged in a duodenal pattern. In a
      prospective, two-center, open-label trial, this study evaluated the efficacy of
      rituximab-combined chemotherapy ([cyclophosphamide, doxorubicin, vincristine, and
      prednisone] or [cyclophosphamide, vincristine, and prednisone]) and prolonged
      treatment with rituximab (R-Chemo+prolongedR) in 14 patients and compared their
      outcomes with those of 15 patients managed with a W&W approach. RESULTS: Four
      patients managed with the W&W plan showed worsening macroscopic findings, lesion
      area enlargement, or clinical stage progression but stayed on this plan because
      they had LTB and experienced no changes in bowel function. In the R
      Chemo+prolongedR group, all patients achieved complete remission; recurrence
      occurred in one patient, who was subsequently managed with the W&W plan because
      of LTB. There were no significant differences in progression-free survival
      between the two groups (P = 0.1045). Overall survival was 100% in both groups.
      CONCLUSIONS: The prognoses of patients with asymptomatic intestinal FL and LTB
      who were managed with a W&W strategy were comparable with those of patients
      receiving R-Chemo+prolongedR.

PMID- 29377266
TI  - Impact of the spectral and spatial properties of natural light on indoor gas
      phase chemistry: Experimental and modeling study.
AB  - The characteristics of indoor light (intensity, spectral, spatial distribution)
      originating from outdoors have been studied using experimental and modeling
      tools. They are influenced by many parameters such as building location,
      meteorological conditions, and the type of window. They have a direct impact on
      indoor air quality through a change in chemical processes by varying the
      photolysis rates of indoor pollutants. Transmittances of different windows have
      been measured and exhibit different wavelength cutoffs, thus influencing the
      potential of different species to be photolysed. The spectral distribution of
      light entering indoors through the windows was measured under different
      conditions and was found to be weakly dependent on the time of day for indirect
      cloudy, direct sunshine, partly cloudy conditions contrary to the light
      intensity, in agreement with calculations of the transmittance as a function of
      the zenithal angle and the calculated outdoor spectral distribution. The same
      conclusion can be drawn concerning the position within the room. The impact of
      these light characteristics on the indoor chemistry has been studied using the
      INCA-Indoor model by considering the variation in the photolysis rates of key
      indoor species. Depending on the conditions, photolysis processes can lead to a
      significant production of radicals and secondary species.

PMID- 29377267
TI  - After 18 months of antiretroviral therapy, total HIV DNA decreases more
      pronouncedly in patients infected by CRF01_AE than in those infected by subtype B
      and CRF07_BC.
AB  - Whether the amount of HIV DNA is associated with the subtype of HIV-1 after
      antiretroviral therapy (ART) has not been reported. In the present study, the
      amount of HIV DNA and RNA and CD4+T counts in blood and semen prior to and after
      18 months of ART were compared in 48 patients infected by CRF01_AE, subtype B or
      CRF07_BC of HIV-1. Viral RNA was suppressed and CD4 cell count recovery achieved
      in all patients. The level of HIV DNA were similar before ART; however, patients
      with CRF01_AE had less HIV DNA after ART than those with subtype B and CRF07_BC
      infection. According to prediction of co-receptor usage by Geno2Pheno and PSSM in
      combination, more than 35.6% of clones for CRF01_AE were predicted as CXCR4-using
      before ART, whereas less than 6% of those for subtype B and CRF07_BC were
      predicted as CXCR4-using. After 18 months of ART, no CXCR4-using clones were
      predicted in any of the subtypes. Despite more HIV RNA and fewer CD4 + T cells in
      patients with CRF01_AE before therapy, no significant differences (P > 0.05) in
      viral RNA or CD4 cell counts were observed between the subtypes after 18 months
      of ART. Thus, 18 months of antiretroviral therapy was more efficient in patients
      with CRF01_AE. Considering that successful ART dramatically reduces the viral
      load in both blood and semen, risks of sexual transmission of HIV were reduced,
      contributing to prevention of rapid spread of HIV among men who have sex with men
      in the region.

PMID- 29377269
TI  - Ginsenoside Rh2 inhibits proliferation and migration of medulloblastoma Daoy by
      down-regulation of microRNA-31.
AB  - This study aimed to investigate the effects of ginsenoside Rh2 on proliferation,
      apoptosis, and migration of the human medulloblastoma cell line Daoy, as well as
      to explore the potential mechanisms of the effects. The human medulloblastoma
      cell line Daoy was cultured in vitro and treated with or without ginsenoside Rh2.
      CCK-8 assay was performed to investigate the effect of Rh2 on cell survival using
      a cell counting Kit-8. Cell proliferation was assessed by BrdU assay. Cell
      apoptosis was determined using flow cytometry analysis. Cell migration was
      detected using a modified two-chamber migration assay. MiR-31 mimic and the NC
      control were transfected into Daoy cells and detected by qRT-PCR. The expression
      of Wnt3a, Wnt5a, and beta-catein was detected by Western blot analysis. Rh2
      efficiently suppressed the proliferation and migration, and promoted the
      apoptosis of Daoy cells. Additionally, Rh2 could down-regulate miR-31. miR-31
      overexpression reversed the effects of Rh2 on proliferation, apoptosis and
      migration of Daoy cells, and activated the Wnt/beta-catein signaling pathways in
      Daoy cells. Rh2 could inhibit the proliferation and migration, and induce
      apoptosis of Daoy medulloblastoma cells through down-regulation of miR-31 to
      inactivate the Wnt/beta-catein signaling pathway. Therefore, Rh2 may have a
      utility in clinical applications for the treatment of medulloblastoma.

PMID- 29377268
TI  - Elevated donor plasminogen activator inhibitor-1 levels and the risk of primary
      graft dysfunction.
AB  - Primary graft dysfunction (PGD) following lung transplantation is associated with
      elevated recipient plasma levels of plasminogen activator inhibitor-1 (PAI-1) and
      the receptor for advanced glycation end products (RAGE). However, the
      significance of these biomarkers in the donor plasma is uncertain. We
      hypothesized that elevated donor plasma levels of PAI-1 and RAGE would be
      associated with recipient PGD. We carried out a prospective unmatched case
      control study of double-lung transplant recipients between May 2014 and September
      2015. We compared donor plasma levels of PAI-1 and RAGE using rank-sum tests and
      t tests, in 12 recipients who developed PGD grade 2 or 3 within 72 hours
      postoperatively with 13 recipients who did not. Recipients who developed PGD had
      higher donor plasma levels of PAI-1 than recipients who did not (median 2.7 ng/mL
      vs 1.4; P = .03). Recipients with PGD also had numerically higher donor plasma
      levels of RAGE than recipients without PGD, although this difference did not
      achieve statistical significance (median 1061 pg/mL vs 679; P = .12). Systemic
      inflammatory responses in the donor, as reflected by elevated plasma levels of
      PAI-1, may contribute to the risk of developing PGD. Rapid biomarker assessment
      of easily available plasma samples may assist in donor lung selection and risk
      stratification.

PMID- 29377270
TI  - Frontal fibrosing alopecia after antiandrogen hormonal therapy in a male patient.

PMID- 29377271
TI  - Management of achalasia cardia: Expert consensus statements.
AB  - Achalasia cardia (AC) is a frequently encountered motility disorder of the
      esophagus resulting from an irreversible degeneration of neurons. Treatment
      modalities are palliative in nature, and there is no curative treatment available
      for AC as of now. Significant advancements have been made in the management of AC
      over last decade. The introduction of high resolution manometry and per-oral
      endoscopic myotomy (POEM) has strengthened the diagnostic and therapeutic
      armamentarium of AC. High resolution manometry allows for the characterization of
      the type of achalasia, which in turn has important therapeutic implications. The
      endoscopic management of AC has been reinforced with the introduction of POEM
      that has been found to be highly effective and safe in palliating the symptoms in
      short-term to mid-term follow-up studies. POEM is less invasive than Heller's
      myotomy and provides the endoscopist with the opportunity of adjusting the length
      and orientation of esophageal myotomy according to the type of AC. The management
      of achalasia needs to be tailored for each patient, and the role of pneumatic
      balloon dilatation, POEM, or Heller's myotomy needs to be revisited. In this
      review, we discuss the important aspects of diagnosis as well as management of
      AC. The statements presented in the manuscript reflect the cumulative efforts of
      an expert consensus group.

PMID- 29377272
TI  - Successful care and propagation of the endangered amargosa vole (Microtus
      californicus scirpensis) in captivity.
AB  - The Amargosa vole (Microtus californicus scirpensis) is a highlyendangered rodent
      endemic to a small stretch of the California portion of the Amargosa River basin
      in Inyo County's Mojave Desert. Although the Amargosa vole has survived in this
      naturally fragmented ecosystem for thousands of years, recent habitat degradation
      due to land development, water drainage, and marsh exploitation has further
      isolated the species and reduced its available habitat. As part of a conservation
      effort to preserve the species, a captive breeding population was established in
      2014 to serve as an insurance colony and as a source of individuals to release
      into the wild as restored habitat becomes available. As this is the only captive
      colony for this species, there is little published information about appropriate
      care and husbandry for the Amargosa vole. Here we provide information about
      behavior, diet, reproduction, drug sensitivities, and diseases that affect
      successful captive care. We also provide recommendations for housing and disease
      management to preserve natural behaviors and defenses in captive-born animals.

PMID- 29377273
TI  - Increasing kidney donor profile index sequence does not adversely affect medium
      term health-related quality of life after kidney transplantation.
AB  - BACKGROUND: The United Network for Organ Sharing system allocates deceased donor
      kidneys based on the kidney donor profile index (KDPI), stratified as sequences
      (A <= 20%, B > 20-<35%, C >= 35-<=85%, and D > 85%), with increasing KDPI
      associated with decreased graft survival. While health-related quality of life
      (HRQOL) may improve after transplantation, the effect of donor kidney quality,
      reflected by KDPI sequence, on post-transplant HRQOL has not been reported.
      METHODS: Health-related quality of life was measured using the eight scales and
      physical and mental component summaries (PCS, MCS) of the SF-36(r) Health Survey.
      Multivariable mixed effects models that adjusted for age, gender, rejection, and
      previous transplant and analysis of variance methods tested the effects of time
      and KDPI sequence on post-transplant HRQOL. RESULTS: A total of 141 waitlisted
      adults and 505 recipients (>1700 observations) were included. Pretransplant PCS
      and MCS averaged, respectively, slightly below and within general population
      norms (GPN; 40-60). At 31 +/- 26 months post-transplant, average PCS (41 +/- 11)
      and MCS (51 +/- 11), overall and within each KDPI sequence, were within GPN. KDPI
      sequence was not related to post-transplant HRQOL (P > .134) or its trajectory
      (interaction P > .163). CONCLUSION: Increasing KDPI does not adversely affect the
      medium-term values and trajectories of HRQOL after kidney transplantation. This
      may reassure patients and centers when considering using high KDPI kidneys.

PMID- 29377275
TI  - Regulatory effect of resveratrol and prednisolone on MDR1 gene expression in
      acute lymphoblastic leukemia cell line (CCRF-CEM): An epigenetic perspective.
AB  - Chemotherapy is the most common method to treat leukemia as well as other types
      of human cancers. However, drug resistance has remained as the main challenge
      against the efficacy of treatments. Furthermore, having various adverse effects,
      chemotherapy drugs are becoming replaced by natural modalities for cancer
      therapy. In this regard, herbal components such as resveratrol and prednisolone
      have been identified to sensitize the leukemic cells to programmed cell death
      through a set of complex processes. In this study, we have examined DNA
      methylation on the human multidrug resistance gene 1 (MDR1) as a well-known
      marker for cellular drug resistance. We evaluated the effect of resveratrol and
      prednisolone on DNA methylation patterns of MDR1 gene promoter in the CCRF-CEM
      cell line as a representative for acute lymphoblastic leukemia. The study was
      aimed to clarify whether the MDR1 gene expression is regulated via DNA promoter
      methylation as a potential underlying mechanism, following exposure to
      resveratrol and prednisolone. Our data revealed that despite a strong influence
      to down-regulate the MDR1 expression, Resveratrol and Prednisolone did not alter
      the methylation pattern, suggesting other regulatory mechanisms in controlling
      the MDR1 expression in CCRF-CEM cell line. Unchanged status of DNA methylation of
      MDR1 gene may suggest that Resveratrol and Prednisolone causes the gene
      expression changes through a distinct mechanism which requires further studies to
      be understood. A more detailed understanding of the mechanisms beyond the
      regulation of the genes involved in cancer formation will help to design novel
      therapeutic strategies to fight the human cancers.

PMID- 29377274
TI  - All-oral direct-acting antiviral therapy against hepatitis C virus (HCV) in human
      immunodeficiency virus/HCV-coinfected subjects in real-world practice: Madrid
      coinfection registry findings.
AB  - : We evaluated treatment outcomes in a prospective registry of human
      immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients treated with
      interferon-free direct-acting antiviral agent-based therapy in hospitals from the
      region of Madrid between November 2014 and August 2016. We assessed sustained
      viral response at 12 weeks after completion of treatment and used multivariable
      logistic regression to identify predictors of treatment failure. We evaluated
      2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated
      cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes
      were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens
      included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%),
      dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens
      (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients
      discontinued therapy owing to adverse events. The frequency of sustained viral
      response by intention-to-treat analysis was 92.0% (95% confidence interval, 90.9%
      93.1%) overall, 93.8% (92.4%-95.0%) for no cirrhosis, 91.0% (88.8%-92.9%) for
      compensated cirrhosis, and 80.8% (73.7%-86.6%) for decompensated cirrhosis. The
      factors associated with treatment failure were male sex (adjusted odds ratio,
      1.75; 95% confidence interval, 1.14-2.69), Centers for Diseases Control and
      Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12
      2.41), a baseline cluster of differentiation 4-positive (CD4+) T-cell count
      <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35-3.92), an HCV
      RNA load >=800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval,
      1.14-2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence
      interval, 0.96-1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95%
      confidence interval, 1.76-4.87), and the use of SOF plus simeprevir, SOF plus
      ribavirin, and simeprevir plus daclatasvir. CONCLUSION: In this large real-world
      study, direct-acting antiviral agent-based therapy was safe and highly effective
      in coinfected patients; predictors of failure included gender, human
      immunodeficiency virus-related immunosuppression, HCV RNA load, severity of liver
      disease, and the use of suboptimal direct-acting antiviral agent-based regimens.
      (Hepatology 2018;68:32-47).

PMID- 29377276
TI  - A new automated turbidimetric immunoassay for the measurement of canine C
      reactive protein.
AB  - BACKGROUND: In dogs, as in humans, C-reactive protein (CRP) is a major acute
      phase protein that is rapidly and prominently increased after exposure to
      inflammatory stimuli. CRP measurements are used in the diagnosis and monitoring
      of infectious and inflammatory diseases. OBJECTIVES: The study aim was to develop
      and validate a turbidimetric immunoassay for the quantification of canine CRP
      (cCRP), using canine-specific reagents and standards. METHODS: A particle
      enhanced turbidimetric immunoassay was developed. The assay was set up in a fully
      automated analyzer, and studies of imprecision, limits of linearity, limits of
      detection, prozone effects, and interferences were carried out. The new method
      was compared with 2 other commercially available automated immunoassays for cCRP:
      one turbidimetric immunoassay (Gentian CRP) and one point-of-care assay based on
      magnetic permeability (Life Assays CRP). RESULTS: The within-run and between-day
      imprecision were <1.7% and 4.2%, respectively. The assay quantified CRP
      proportionally in an analytic range up to 150 mg/L, with a prozone effect
      appearing at cCRP concentrations >320 mg/L. No interference from hemoglobin (20
      g/L), triglycerides (10 g/L), or bilirubin (150 mg/L) was detected. Good
      agreement was observed between the results obtained with the new method and the
      Gentian cCRP turbidimetric immunoassay. CONCLUSIONS: The new turbidimetric
      immunoassay (Turbovet canine CRP, Acuvet Biotech) is a rapid, robust, precise,
      and accurate method for the quantification of cCRP. The method can be easily set
      up in automated analyzers, providing a suitable tool for routine clinical use.

PMID- 29377278
TI  - Hypertrichosis of the pinnae in a patient using panitumumab.

PMID- 29377277
TI  - Business of dialysis and the role of the medical director.
AB  - Since the inception of the Medicare End Stage Renal Disease Program in 1972, the
      medical director has been an important leader in the dialysis unit. The initial
      duties of the medical director were focused on quality and safety but were
      gradually expanded over the decades to include the development and oversight of
      protocols to manage metabolic bone disease and anemia. As the total cost of ESRD
      care has escalated, there have been progressive attempts to control costs through
      additional bundling and the creation of alternative payment schemes. While we
      await the financial and clinical outcomes of these initiatives, the medical
      director's role continues to expand in scope and now includes an enhanced role
      for not only clinical outcomes but financial outcomes as well.

PMID- 29377279
TI  - Zebrafish larvae as a model to demonstrate secondary iron overload.
AB  - OBJECTIVES: Thalassemia is the most common genetically inherited blood disorder
      arising from a defect in hemoglobin production, resulting in ineffective
      erythropoiesis and severe hemolytic anemia. While transfusion therapy corrects
      the anemia, it gives rise to secondary iron overload. Current iron chelation
      therapy performed using deferoxamine, and the efficiency of this drug was
      demonstrated here using the zebrafish animal model. METHODS: Zebrafish larvae
      were exposed for 3 days to iron [100 MUmol L-1 ferric ammonium citrate; 3-6 days
      post fertilization (dpf)]. Then, iron treated larvae were exposed to 100 MUmol L
      1 deferoxamine for 3 days (6-9 dpf). Total tissue iron concentration in the whole
      larvae, assessed by three different assays; inductively coupled plasma mass
      spectrometry, colorimetry (spectrophotometry), and microscopy using iron staining
      followed by imaging and quantification. RESULTS: The three assays showed that
      iron treatment alone resulted in a significant increase in total iron.
      Deferoxamine treatment of the iron-loaded zebrafish larvae showed a significant
      decrease in total iron concentration. CONCLUSION: This study presented a clear
      evidence of the effectiveness of zebrafish larvae to use as a tool to study iron
      overload and open the door for studying the efficiency of potential new iron
      chelating compounds other than commercially available ones.

PMID- 29377280
TI  - A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex
      with men: a cohort study in Paris.
AB  - BACKGROUND: Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men
      and is associated with Kaposi's sarcoma-associated herpesvirus (KSHV). In low
      endemic countries, KSHV infects predominantly men having sex with men (MSM).
      OBJECTIVES: To describe a cohort of classic Kaposi sarcoma in a low-endemic area
      for KSHV, to highlight the features of CKS in MSM and identify prognostic
      factors. METHODS: Retrospective single-centre study of CKS cases. We compared MSM
      to heterosexual patients. Then, we divided the patients into two subgroups, those
      requiring a systemic treatment and the others, and we performed univariate and
      multivariate analyses to determine aggressiveness of CKS. RESULTS: Between 2006
      and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9
      years; sex ratio (M/F) was 6.4, and 28% were MSM; MSM patients were younger (P =
      0.02), less often originated from endemic areas (P < 0.0001). KS was less severe
      (P = 0.04), required more often a local treatment than a systemic one (P = 0.03).
      On multivariate analysis, CD4 T-cell count > 500/mm3 at baseline was associated
      with a reduced risk of severe evolution. CONCLUSION: First CKS cohort in low
      endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count
      was found to correlate with prognosis.

PMID- 29377281
TI  - ER stress mediated regulation of miR23a confer Hela cells better adaptability to
      utilize glycolytic pathway.
AB  - Cancer cells exhibit increased dependency on aerobic glycolysis, a phenomenon
      referred as the "Warburg effect" and therefore, blocking glycolysis by using non
      metabolizable analogues of glucose, like 2-Deoxy glucose (2-DG), has been
      proposed to be of huge therapeutic importance. One of the major drawbacks of
      using 2-DG as a chemotherapeutic agent is that it can induce ER stress. ER stress
      is a hall mark in many solid tumors and the unfolded protein response (UPR)
      associated with it initiates many survival mechanisms in cancer cells. In the
      present study, we report a novel survival mechanism associated with ER stress, by
      which the cancer cells become more adapted to aerobic glycolysis. When ER stress
      was induced in Hela cells by treating them with 2-DG or Thapsigargin (TG) the
      expression and activity of LDH was significantly up regulated, conferring the
      cells a greater glycolytic potential. A simultaneous decrease was observed in the
      expression of miR-23a, which was predicted in silico to have target site on the
      3'UTR of LDH A and B mRNAs. miRNA over expression studies and mRNA degradation
      assays suggest that miR-23a could target LDH A and LDH B mRNAs. Further on the
      basis of our results and previous scientific reports, we propose that "c-Myc,"
      which is over expressed during ER stress, repress the expression of miR-23a,
      which in turn regulates the expression of its target genes viz., LDH A and LDH B,
      thereby making the cells more competent to survive in tumor microenvironment,
      which requires efficient use of aerobic glycolysis.

PMID- 29377282
TI  - Impact of intraoperative cytokine adsorption on outcome of patients undergoing
      orthotopic heart transplantation-an observational study.
AB  - AIM: The aim of this study was to assess the influence of intraoperative cytokine
      adsorption on the perioperative vasoplegia, inflammatory response and outcome
      during orthotopic heart transplantation (OHT). METHODS: Eighty-four OHT patients
      were separated into the cytokine adsorption (CA)-treated group or controls.
      Vasopressor demand, inflammatory response described by procalcitonin and C
      reactive protein, and postoperative outcome were assessed performing propensity
      score matching. RESULTS: In the 16 matched pairs, the median noradrenaline
      requirement was significantly less in the CA-treated patients than in the
      controls on the first and second postoperative days (0.14 vs 0.3 MUg*kg-1 *min-1
      , P = .039 and 0.06 vs 0.32 MUg*kg-1 *min-1 , P = .047). The inflammatory
      responses were similar in the two groups. There was a trend toward shorter length
      of mechanical ventilation and intensive care unit (ICU) stay in the CA-treated
      group compared to the controls. No difference in adverse events was observed
      between the two groups. However, the frequency of renal replacement therapy was
      significantly less in the CA-treated patients than in the controls (P = .031).
      CONCLUSIONS: Intraoperative CA treatment was associated with reduced vasopressor
      demand and less frequent renal replacement therapy with a favorable tendency in
      length of mechanical ventilation and ICU stay. CA treatment was not linked to
      higher rates of adverse events.

PMID- 29377283
TI  - Soluble CD14, CD163, and CD27 biomarkers distinguish ART-suppressed youth living
      with HIV from healthy controls.
AB  - OBJECTIVE: To define inflammatory pathways in youth living with HIV infection
      (YLWH), assessments of biomarkers associated with lymphocyte and macrophage
      activation, vascular injury, or bone metabolism were performed in YLWH in
      comparison with healthy controls (HC). DESIGN:  Longitudinal multicenter study
      comparing biomarkers in YLWH suppressed on antiretroviral therapy (ART), those
      with ongoing viral replication, and HC were compared using single blood samples
      obtained at end of study. METHODS:  Twenty-three plasma proteins were measured by
      ELISA or multiplex assays. Principal component analysis (PCA) was used to define
      contributions of individual biomarkers to define outcome groups. RESULTS:  The
      study cohort included 129 predominantly African American, male participants, 21
      25 years old at entry. Nine biomarkers of lymphocyte and macrophage activation
      and cardiovascular injury differed between HC and YLWH. Significant positive
      correlations were identified between lymphocyte and macrophage activation
      biomarkers among HC and YLWH. Correlations distinct to YLWH were predominantly
      between biomarkers of macrophage and vascular inflammation. PCA of outcome groups
      showed HC and suppressed YLWH clustering together for lymphocyte activation
      biomarkers, whereas macrophage activation markers showed all YLWH clustering
      distinct from HC. Cardiovascular biomarkers were indistinguishable across groups.
      Averaged variable importance projection to assess single biomarkers that
      maximally contribute to discriminate among outcome groups identified soluble
      CD27, CD14, and CD163 as the 3 most important with TNFalpha and LPS also highly
      relevant in providing separation. CONCLUSIONS:  Soluble inflammatory and
      lymphocyte biomarkers sufficiently distinguish YLWH from HC. Persistent
      macrophage activation biomarkers may provide a means to monitor consequences of
      HIV infection in fully suppressed YLWH.

PMID- 29377285
TI  - Retrospective study on the correlation between 18-fluorodeoxyglucose uptake in
      positron emission tomography-computer tomography and tumour volume, cytological
      activity as assessed with Ki-67 and GLUT-1 staining in 10 cases of Merkel cell
      carcinoma.

PMID- 29377286
TI  - Diagnostic approach to subcutaneous nodules in patients with neuroendocrine
      tumours treated with depot somatostatin analogs: a cross-sectional study.
AB  - BACKGROUND: The presence of cutaneous nodules in patients with
      gastroenteropancreatic neuroendocrine tumours (GEP-NETs) receiving depot
      somatostatin analogs (SSAs) is a diagnostic challenge as differential diagnosis
      between injection site reactions and metastases is essential. OBJECTIVE: To
      characterize the clinical, radiological, cytological and histopathological
      features of subcutaneous nodules in patients with GEP-NETs treated with SSAs.
      MATERIALS AND METHODS: Retrospective, cross-sectional study of patients with GEP
      NETs treated with SSAs in whom subcutaneous nodules were detected on routine
      abdominal computed tomography (CT) scans. High resolution and colour Doppler
      ultrasonography was performed. Those patients with inconclusive radiological
      studies went through fine-needle aspiration cytology (FNAC) and/or biopsy.
      RESULTS: Twelve patients (five males, seven females) were included (six midgut
      carcinoid NETs, six pancreatic NETs). Three patients received intramuscular depot
      octreotide, seven subcutaneous lanreotide, and two both treatments. CT scan
      findings were nonspecific. Sonography revealed a hyperechoic pattern in recent
      injections, and a hypoechoic pattern with a characteristic hyperechoic peripheral
      rim in long-term injections (more than 3 months after injection). On colour
      Doppler sonography, nodules showed no signs of intralesional vascularity. Fine
      needle aspiration cytology (FNAC) was performed in five patients, revealing a
      characteristic acellular proteinaceous material. Biopsy in four patients showed
      different reactional infiltrates around the acellular material. CONCLUSIONS: High
      resolution and colour Doppler ultrasonography may be very useful for the
      differential diagnosis of subcutaneous nodules in patients with GEP-NETs treated
      with SSAs. FNAC and a biopsy are useful tests for confirmation of the diagnosis
      in patients with inconclusive findings. We propose a management algorithm.

PMID- 29377287
TI  - Multimodal assessment of orbital immune cell infiltration and tissue remodeling
      during development of graves disease by 1 H19 F MRI.
AB  - PURPOSE: To evaluate key molecular and cellular features of Graves orbitopathy
      (GO) by simultaneous monitoring of alterations in morphology, inflammatory
      patterns, and tissue remodeling. METHODS: To this end, we utilized a murine model
      of GO induced by immunization with a human thyroid-stimulating hormone receptor A
      subunit plasmid. Altogether, 52 mice were used: 27 GOs and 25 controls (Ctrl)
      immunized with beta-galactasidose plasmid. From these, 17 GO and 12 Ctrl mice
      were subjected to multimodal MRI at 9.4T, whereas 23 mice only underwent
      histology. Beyond anatomical hydrogen-1 (1 H) MRI, we employed transverse
      relaxation time (T2 ) mapping for visualization of edema, chemical exchange
      saturation transfer (CEST) for detection of hyaluronan, and fluorine-19 (19 F)
      MRI for tracking of in situ-labeled immune cells after intravenous injection of
      perfluorcarbons (PFCs). RESULTS: 1 H/19 F MRI demonstrated substantial
      infiltration of PFC-loaded immune cells in peri and retro-orbital regions of GO
      mice, whereas healthy Ctrls showed only minor 19 F signals. In parallel, T2
      mapping indicated onset of edema in periorbital tissue and adjacent ocular glands
      (P = 0.038/0.017), which were associated with enhanced orbital CEST signals in GO
      mice (P = 0.031). Concomitantly, a moderate expansion of retrobulbar fat (P =
      0.029) was apparent; however, no signs for extraocular myopathy were detectable.
      19 F MRI-based visualization of orbital inflammation exhibited the highest
      significance level to discriminate between GO and Ctrl mice (P = 0.006) and
      showed the best correlation with the clinical score (P = 0.0007). CONCLUSION: The
      present approach permits the comprehensive characterization of orbital tissue and
      holds the potential for accurate GO diagnosis in the clinical setting. Magn Reson
      Med 80:711-718, 2018. (c) 2018 International Society for Magnetic Resonance in
      Medicine.

PMID- 29377289
TI  - Kidney allograft survival outcomes in combined intestinal-kidney transplant: An
      analysis of the UNOS/OPTN database 2000-2014.
AB  - BACKGROUND AND OBJECTIVES: Intestinal transplants carry a high
      morbidity/mortality. Kidney allograft outcomes after combined intestinal (IT)
      with kidney transplant (CIKT) remain largely uninvestigated. MATERIALS AND
      METHODS: The UNOS STAR database was queried to identify all such combined organ
      transplants from 2000 to 2015. RESULTS: Out of a total 2215 (51.4% peds vs 48.6%
      adults) intestinal transplants, 111 (5.0%) CIKT were identified (32.4% peds vs
      67.6% adults). Over the study period of CIKT, a total of 45.9% of these cases
      died with a functioning kidney graft. DGF rate was 9.0%. The 1-year reported
      kidney acute rejection rate was 6.3%. For the entire CIKT population over the
      entire study era, the 1-, 3-, and 5-year unadjusted kidney graft survival was
      57%, 39%, and 34%, while death-censored kidney graft survival was 93%, 90%, and
      86%, respectively. Overall conditional 5-year kidney graft survival (defined as 1
      year kidney graft survival) was 58%. Overall, patient survival was significantly
      lower in recipients of CIKT compared to intestinal transplant (IT) (P < .005);
      However, the 5-year conditional (1 year kidney graft) patient survival in adults
      was not significantly different between IT and CIKT overall (P = .194).
      CONCLUSIONS: Kidney allograft survival is primarily dependent on 1-year patient
      survival. Guidelines regarding allocation of kidney allografts in CIKT need to
      take into consideration utility and urgency.

PMID- 29377288
TI  - Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism
      genes by human macrophages.
AB  - Several lines of evidence link macrophage activation and inflammation with
      (monoaminergic) nervous systems in the etiology of depression. IFN treatment is
      associated with depressive symptoms, whereas anti-TNFalpha therapies elicit
      positive mood. This study describes the actions of 2 monoaminergic
      antidepressants (escitalopram, nortriptyline) and 3 anti-inflammatory drugs
      (indomethacin, prednisolone, and anti-TNFalpha antibody) on the response of human
      monocyte-derived macrophages (MDMs) from 6 individuals to LPS or IFN-alpha.
      Expression profiling revealed robust changes in the MDM transcriptome (3294 genes
      at P < 0.001) following LPS challenge, whereas a more limited subset of genes
      (499) responded to IFNalpha. Contrary to published reports, administered at
      nontoxic doses, neither monoaminergic antidepressant significantly modulated the
      transcriptional response to either inflammatory challenge. Each anti-inflammatory
      drug had a distinct impact on the expression of inflammatory cytokines and on the
      profile of inducible gene expression-notably on the regulation of enzymes
      involved in metabolism of tryptophan. Inter alia, the effect of anti-TNFalpha
      antibody confirmed a predicted autocrine stimulatory loop in human macrophages.
      The transcriptional changes were predictive of tryptophan availability and
      kynurenine synthesis, as analyzed by targeted metabolomic studies on cellular
      supernatants. We suggest that inflammatory processes in the brain or periphery
      could impact on depression by altering the availability of tryptophan for
      serotonin synthesis and/or by increasing production of neurotoxic kynurenine.

PMID- 29377290
TI  - Self-Assembling of Fmoc-GC Peptide Nucleic Acid Dimers into Highly Fluorescent
      Aggregates.
AB  - The study of molecules that self-assemble through noncovalent interactions is one
      of the most attractive topics in supramolecular chemistry. The use of short
      peptides or modified nucleotides as building blocks for the aggregates is
      particularly intriguing because these are very easy to synthesize; moreover,
      subtle changes in the chemical structure of such building blocks may drastically
      affect the properties of the aggregates. The ability of peptide nucleic acids
      (PNA) to aggregate has been very little explored, despite its practical
      applications. In this work we investigated the self-assembling properties of a
      PNA dimer, conjugated at the N-terminus to a fluorenylmethoxycarbonyl group. This
      PNA dimer forms nano-aggregates at low concentration in CHCl3 /CH3 OH mixtures.
      The aggregates retain very interesting fluorescent properties (high quantum yield
      in the visible region with lifetimes on the nanosecond scale), which make them
      promising materials for applications in optoelectronics.

PMID- 29377292
TI  - Glucose-6-phosphate-dehydrogenase deficient red blood cell units are associated
      with decreased posttransfusion red blood cell survival in children with sickle
      cell disease.
AB  - Chronic transfusion therapy (CTT) for sickle cell disease (SCD) reduces disease
      morbidity by suppressing the amount of circulating hemoglobin S (HbS)-containing
      red blood cells (RBC). The effectiveness of CTT depends on the rate of RBC
      clearance. Glucose-6-phosphate dehydrogenase (G6PD) deficient donor RBC may
      exhibit increased hemolysis, but it is unknown if transfusion of these units
      results in less effective transfusion outcomes in SCD. Children with SCD on CTT
      were followed prospectively for multiple transfusions. G6PD activity of
      transfused units was measured prior to expiration date. HbA clearance (DeltaHbA)
      was calculated as the difference of estimated posttransfusion HbA to the
      pretransfusion HbA of the subsequent transfusion episode. Sixty-two patients
      received 388 transfusions. Of 755 RBC units, 687 (91%) had normal G6PD (>60%
      activity), 38 (5%) had moderately low G6PD (10-60% activity), and 30 (4%) had
      severely low G6PD (<10% activity). Of 358 evaluable transfusions, 54 (15%)
      included >=1 G6PD deficient units, and 22 (6%) had >=1 severely deficient units.
      The proportion of the transfusion episode consisting of G6PD deficient units was
      associated with increased DeltaHbA for all G6PD deficient units (P = .05) and for
      severely G6PD deficient units (P = .0070). In multivariate mixed effects
      modeling, DeltaHbA was positively associated with severely G6PD deficient units
      (P = .0074) and RBC alloimmunization (P = .03) and negatively associated with
      recipient splenectomy (P = .015). Higher DeltaHbA was associated with higher HbS
      and reticulocyte counts at the subsequent transfusion episode. In conclusion,
      G6PD deficient RBC transfusions may have shorter in vivo survival and adversely
      affect the suppression of sickle erythropoiesis.

PMID- 29377293
TI  - A study of androgenic signs and disorders in Greek female patients with acne.

PMID- 29377291
TI  - Stereopsis: are we assessing it in enough depth?
AB  - The assessment of stereoacuity is an integral part of the ophthalmic assessment,
      with the responses used to inform clinical management decisions. Stereoacuity
      impacts on many aspects of life, but there are discrepancies reported where
      people without measurable stereoacuity report appreciating 3-D vision. This could
      be due, in part, to the presentation of the stimuli. A literature review was
      undertaken to evaluate current assessment techniques, how they relate to patient
      outcomes, identify the limitations of current tests and discuss how they could be
      improved. Recent evidence has been collated on currently available tests, used
      commonly within vision clinics, with normative data provided allowing responses
      to the tests to be interpreted. The relevance of the results is evaluated in
      relation to a range of outcomes, where a reduced level of stereopsis has a
      negative impact on the ability of an individual to perform many tasks, and can
      lead to an increase in difficulty interacting in the world. Current tests are
      limited in the aspects of stereoacuity they assess and their ability to precisely
      measure stereopsis. The world is not static, yet clinical tests are limited to
      measuring static stereoacuity, even though higher grades of depth perception can
      be identified in the presence of changing depth. Presentation methods of
      stereoacuity tests have remained similar over time, with a limited number of
      disparity levels assessed. New assessment methods are becoming available that
      include automated staircase testing to present multiple levels of disparity using
      digital technology. Current clinical tests are limited in their presentation, and
      are poor at detecting/measuring stereoacuity in those with limited stereopsis.
      Given the relevance of the stereoacuity measurement to management choices and
      functional outcomes, new testing methods would be beneficial to fully assess
      stereoacuity, both static and dynamic.

PMID- 29377294
TI  - Increased ceruloplasmin expression caused by infiltrated leukocytes, activated
      microglia, and astrocytes in injured female rat spinal cords.
AB  - Ceruloplasmin (Cp), an enzyme containing six copper atoms, has important roles in
      iron homeostasis and antioxidant defense. After spinal cord injury (SCI), the
      cellular components in the local microenvironment are very complex and include
      functional changes of resident cells and the infiltration of leukocytes. It has
      been confirmed that Cp is elevated primarily in astrocytes and to a lesser extent
      in macrophages following SCI in mice. However, its expression in other cell types
      is still not very clear. In this manuscript, we provide a sensible extension of
      these findings by examining this system within a female Sprague-Dawley rat model
      and expanding the scope of inquiry to include additional cell types. Quantitative
      reverse transcription polymerase chain reaction and Western blot analysis
      revealed that the Cp mRNA and protein in SCI tissue homogenates were quite
      consistent with prior publications. However, we observed that Cp was expressed
      not only in GFAP+ astrocytes (consistent with prior reports) but also in CD11b+
      microglia, CNPase+ oligodendrocytes, NeuN+ neurons, CD45+ leukocytes, and CD68+
      activated microglia/macrophages. Quantitative analysis proved that infiltrated
      leukocytes, activated microglia/macrophages, and astrocytes should be the major
      sources of increased Cp.

PMID- 29377295
TI  - Basal cell carcinoma of the scrotum: an important but easily overlooked entity.

PMID- 29377296
TI  - Genipin ameliorates diet-induced obesity via promoting lipid mobilization and
      browning of white adipose tissue in rats.
AB  - Genipin is the major active component of Gardeniae fructus and has been shown to
      ameliorate diabetes and insulin resistance in rat models. In this study, we first
      investigated the effect of genipin on obesity and the related lipid metabolism
      mechanisms in diet-induced obese rats. Our results showed that genipin reduced
      body weight, food intake, and visceral fat mass; ameliorated dyslipidemia,
      glucose intolerance, insulin intolerance, adipocyte hypertrophy, and hepatic
      steatosis; and reduced serum tumor necrosis factor-alpha level in diet-induced
      obese rats. Quantitative real-time reverse-transcription polymerase chain
      reaction results further illustrated that genipin promoted lipolysis and beta
      oxidation of fatty acid by upregulating gene expressions of hormone-sensitive
      lipase and adipose triglyceride lipase in white adipose tissue (WAT) and
      peroxisome proliferator-activated receptor-alpha and carnitine
      palmitoyltransferase 1alpha in hepatic tissue. Moreover, genipin promoted
      browning of WAT by upregulating the mRNA and protein levels of uncoupling protein
      1 and PRD1-BF1-RIZ1 homologous domain containing 16 in WAT. Additionally, genipin
      inhibited gene expressions of activin receptor-like kinase 7, tumor necrosis
      factor-alpha, and interlukin-6 in WAT. These results indicated that genipin had a
      potential therapeutic role in obesity, in which regulation of lipid mobilization
      and browning of WAT were involved.

PMID- 29377297
TI  - Patch testing in facial dermatitis using Chinese Baseline Series (60 allergens)
      and Cosmetic Series (58 allergens).

PMID- 29377298
TI  - Bimetallic d10 -Metal Complexes of a Bipyridine Substituted N-Heterocyclic
      Carbene.
AB  - The hybrid ligand 3-(2,2'-bipyridine-6-ylmethyl)-1-mesityl-1H-imidazolylidene
      (NHCBipy ) featuring both carbene and N-donor sites, was selectively complexed
      with various d10 metal cations in order to examine its coordination behavior with
      regard to homo and heterometallic structures. Respective silver complexes can be
      obtained by the silver oxide route and are suitable transmetallation reagents for
      the synthesis of gold(I) compounds. Starting from the mononuclear complexes
      [(NHCBipy )AuCl], [(NHCBipy )Au(C6 F5 )] and [(NHCBipy )2 Au][ClO4 ], open-chain
      as well as cyclic heterobimetallic complexes containing Cu+ , Ag+ , Zn2+ , Cd2+ ,
      and Hg2+ were synthesized. Furthermore, the homobimetallic species [(NHCBipy )2
      M2 ][ClO4 ]2 (M=Cu, Ag) were obtained. All bimetallic compounds were fully
      characterized including single-crystal X-ray analysis. Their photoluminescence
      (PL) properties were investigated in the solid state at temperatures between 15
      and 295 K and compared with those of the mononuclear species. There is a clear
      difference in PL properties between the open chain and the cyclic
      heterobimetallic complexes. The latter species show different PL properties,
      depending on the metals involved. In addition, collision-induced dissociation
      (CID) experiments were performed on electrosprayed cations of the cyclic
      heterobimetallic compounds, to compare the metal binding at the carbene and N
      donor sites.

PMID- 29377299
TI  - Dosage adjustments in patients with psoriasis on adalimumab - a retrospective
      chart review.

PMID- 29377301
TI  - Biomineralization State of Viruses and Their Biological Potential.
AB  - In nature, viruses can realize self-mineralization under metal-ion-abundant
      conditions. Interestingly, the mineralized state is a transition state of the
      virus when the host is not available. Mammalian viruses that share the similar
      chemical properties also stand a chance of transformation into a mineralized
      state. In this review, we focus on the possibility of mammalian viruses to
      undergo mineralization under a physiological environment and the development of
      biomineralized-based virus engineering. We will introduce the effect of
      biomineralization on the physiochemical or biological properties of viruses and
      we will discuss the relationship between mineral composition and biological
      potentials. The new biological prospects of mineralized-state viruses, including
      bypassing biological barriers, protection, and virus-host recognition, will
      provide new insight for the biosecurity and prevention of viral infection. With
      respect to vaccines, the mineralized state can modulate the immune recognition,
      change the immunization route, and elevate the vaccine efficacy. Together, these
      findings of the mineralized state of the virus may lead to a new understanding of
      virus biology, application, and prevention.

PMID- 29377300
TI  - Effects of 6% Tetrastarch and Lactated Ringer's Solution on Extravascular Lung
      Water and Markers of Acute Renal Injury in Hemorrhaged, Isoflurane-Anesthetized
      Healthy Dogs.
AB  - BACKGROUND: Tetrastarch can cause acute kidney injury (AKI) in humans with
      sepsis, but less likely to result in tissue edema than lactated Ringer's solution
      (LRS). OBJECTIVES: Compare effects of volume replacement (VR) with LRS and 6%
      tetrastarch solution (TS) on extravascular lung water (EVLW) and markers of AKI
      in hemorrhaged dogs. ANIMALS: Six healthy English Pointer dogs (19.7-35.3 kg).
      METHODS: Prospective crossover study. Animals underwent anesthesia without
      hemorrhage (Control). Two weeks later, dogs hemorrhaged under anesthesia on 2
      occasions (8-week washout intervals) and randomly received VR with LRS or TS at 3
      : 1 or 1 : 1 of shed blood, respectively. Anesthesia was maintained until 4 hour
      after VR for EVLW measurements derived from transpulmonary thermodilution cardiac
      output. Neutrophil gelatinase-associated lipocalin (NGAL) and creatinine
      concentrations in plasma and urine were measured until 72 hour after VR. RESULTS:
      The EVLW index (mL/kg) was lower at 1 hour after TS (10.0 +/- 1.9) in comparison
      with controls (11.9 +/- 3.4, P = 0.04), and at 4 hour after TS (9.7 +/- 1.9) in
      comparison with LRS (11.8 +/- 2.7, P = 0.03). Arterial oxygen partial pressure-to
      inspired oxygen fraction ratio did not differ among treatments from 0.5 to 4 hour
      after VR. Urine NGAL/creatinine ratio did not differ among treatments and
      remained below threshold for AKI (120,000 pg/mg). CONCLUSIONS AND CLINICAL
      IMPORTANCE: Although TS causes less EVLW accumulation than LRS, neither fluid
      produced evidence of lung edema (impaired oxygenation). Both fluids appear not to
      cause AKI when used for VR after hemorrhage in healthy nonseptic dogs.

PMID- 29377302
TI  - Vaccinium angustifolium (lowbush blueberry) leaf extract increases extravillous
      trophoblast cell migration and invasion in vitro.
AB  - Perturbations to extravillous trophoblast (EVT) cell migration and invasion are
      associated with the development of placenta-mediated diseases. Phytochemicals
      found in the lowbush blueberry plant (Vaccinium angustifolium) have been shown to
      influence cell migration and invasion in models of tumorigenesis and
      noncancerous, healthy cells, however never in EVT cells. We hypothesized that the
      phenolic compounds present in V. angustifolium leaf extract promote trophoblast
      migration and invasion. Using the HTR-8/SVneo human EVT cell line and Boyden
      chamber assays, the influence of V. angustifolium leaf extract (0 to 2 * 104 
      ng/ml) on trophoblast cell migration (n = 4) and invasion (n = 4) was determined.
      Cellular proliferation and viability were assessed using immunoreactivity to Ki67
      (n = 3) and trypan blue exclusion assays (n = 3), respectively. At 20 ng/ml, V.
      angustifolium leaf extract increased HTR-8/SVneo cell migration and invasion (p <
      .01) and did not affect cell proliferation or viability. Chlorogenic acid was
      identified as a major phenolic compound of the leaf extract and the most active
      compound. Evidence from Western blot analysis (n = 3) suggests that the effects
      of the leaf extract and chlorogenic acid on trophoblast migration and invasion
      are mediated through an adenosine monophosphate-activated protein (AMP) kinase
      dependent mechanism. Further investigations examining the potential therapeutic
      applications of this natural health product extract and its major chemical
      compounds in the context of placenta-mediated diseases are warranted.

PMID- 29377303
TI  - Activation of Molecular Oxygen Using Durable Cobalt Encapsulated with Nitrogen
      Doped Graphitic Carbon Shells for Aerobic Oxidation of Lignin-Derived Alcohols.
AB  - It has long been a challenge for activating O2 by transition-metal nanocatalysts,
      which might lose activity due to strong tendency for oxidation. Herein, O2 could
      be activated by durable encapsulated cobalt nanoparticles (NPs) with N-doped
      graphitic carbon shells (Co@N-C), but not by encapsulated cobalt NPs with
      graphitic carbon, exposed cobalt NPs supported on activated carbon, or N-doped
      carbon. Electron paramagnetic resonance, real-time in situ FTIR spectroscopy, and
      mass spectrometry measurements demonstrated the generation of the highly active
      superoxide radical, O2.- . This unique ability enables Co@N-C to afford an
      excellent catalytic performance in model aerobic oxidation of monomeric lignin
      derived alcohols. Further analysis elucidated that encapsulated cobalt and
      nitrogen-doped graphitic carbon might contribute to the capacity through
      influencing the electronic properties of outer layers. Moreover, through
      isolation by N-doped graphitic carbon shells, the inner metallic cobalt NPs are
      inaccessible in term of either alcohols or oxygenated products, and a distinctive
      resistance to leaching and agglomeration has been achieved.

PMID- 29377304
TI  - Regulation of human trophoblast cell syncytialization by transcription factors
      STAT5B and NR4A3.
AB  - In human trophoblast cells, cyclic AMP or its inducer forskolin (FSK) activates
      two downstream signaling molecules, protein kinase A (PKA) and exchange protein
      directly activated by cAMP (EPAC), both of which induce syncytialization, cell
      fusion, and the production of human chorionic gonadotropin (hCG) and
      progesterone. However, a transcription factor other than GCM1 and molecular
      mechanisms associated with these events have not been well characterized. To
      identify novel transcription factors involved in syncytialization of cAMP
      stimulated human choriocarcinoma BeWo cells, the microarray analysis was
      performed with RNAs extracted from PKA- or EPAC-selective cAMP analog-stimulated
      BeWo cells, from which two up-regulated transcription factors, STAT5 and NR4A3,
      were found. The knockdown of STAT5B decreased FSK-induced cell fusion and the
      expression of syncytialization markers, CGB, syncytin1, syncytin2, GCM1, and
      OVOL1, but NR4A3 knockdown increased FSK-induced cell fusion and the expression
      of CGB and syncytin2. These findings indicated that cAMP-PKA up-regulated STAT5B,
      followed by increase in syncytin2 expression through GCM1 and OVOL1, resulting in
      cell fusion and hCG production, while cAMP-PKA-up-regulated NR4A3 could decrease
      syncytin2 expression, and suggested that both positive and negative effects of
      STAT5B and NR4A3, respectively, are required to control the degree of
      syncytialization in human trophoblast cells.

PMID- 29377305
TI  - Calbindin-D28K mediates 25(OH)D3/VDR-regulated bone formation through MMP13 and
      DMP1.
AB  - Calcium binding protein calbindin-D28K (CaBP28K) mediates the relationship
      between vitamin D and calcium, but its mechanism remains unclear during bone
      formation. The present study reports that maternal CaBP28K levels were positively
      correlated with paired umbilical cord CaBP28K levels. In addition, CaBP28K levels
      were positively correlated with the body length, and head and chest
      circumferences of neonates, but negatively correlated with maternal 25(OH)D3
      levels. CaBP28K was also downregulated in MC3T3-E1 osteoblasts when treated with
      1,25(OH)2D or VDR overexpression, but was upregulated in the femur of
      1alpha(OH)ase(-/-) mice. Furthermore, it was found CaBP28K may influence cell
      differentiation and matrix formation through the regulation of DMP1 and the
      interaction with MMP13 in osteoblasts. This suggests that CaBP28K could be a
      candidate for the negative role of 1,25(OH)2D/VDR in regulating bone mass.

PMID- 29377306
TI  - Limb asymmetry during recovery from anterior cruciate ligament reconstruction.
AB  - There is limited literature that follows a population of Anterior Cruciate
      Ligament Reconstruction (ACLR) patients through recovery. Our aim was to examine
      differences in movement and loading patterns across time and between limbs over
      four visits during 12 months post-ACLR. We hypothesized that kinematic and
      kinetic data during a stop-jump would have time- and limb-dependent differences
      through 12 months post-surgery. Twenty-three ACLR athletes performed five
      vertical stop-jumps at 4, 5, 6, and 12 months post-op with motion capture and
      force plate data collection. The peak knee flexion (PKF) was different between
      the 4 and 12, 5 and 6, and the 5 and 12 month visits with earlier months
      exhibiting higher PKF. The peak vertical ground reaction force (vGRF) was lower
      at 4 than at 5 and 6 months. The peak posterior ground reaction force (pGRF) was
      lower at 4 months than all other visits. Frontal knee and sagittal hip range of
      motion (ROM) were different between 12 months and each previous visit.
      Asymmetries were present in peak vGRF, peak knee extension moment and impulse up
      to 12 months. The loading rate and peak pGRF demonstrated between limb
      differences up to 6 months; limb stiffness demonstrated differences up to 5
      months post-ACLR. PKF was only asymmetric at the 4 month visit. While some
      variables improved in the 12 months post-ACLR, limb asymmetries in peak knee
      extension moment, peak vGRF and impulse persisted up to 12 months. Additionally,
      frontal plane knee and sagittal hip ROM had not normalized at 12 months. (c) 2018
      Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res
      36:1887-1893, 2018.

PMID- 29377307
TI  - Stable Organic (Bi)Radicals by Delocalization of Spin Density into the Electron
      Poor Chromophore Core of Isoindigo.
AB  - The first isoindigo (bi)radicals were obtained by proton coupled oxidation of
      their 4-hydroxyaryl substituted precursors. Optical and magnetic spectroscopic
      studies revealed a singlet open-shell biradicaloid electronic ground state for
      the bisphenoxyl-isoindigo (<s2 >=1.20) with a small singlet-triplet energy gap of
      0.065 eV and a large biradical character of y=0.79 that was corroborated by
      temperature-dependent EPR spectroscopy and quantum chemical calculations. The
      concept of kinetic blocking of the radical centers and delocalization of spin
      density into the electron-withdrawing chromophore core of isoindigo offers an
      entry into a new class of exceptionally stable open-shell functional materials
      based on organic colorants.

PMID- 29377308
TI  - Solution, Solid-State, and Computational Analysis of Agostic Interactions in a
      Coherent Set of Low-Coordinate Rhodium(III) and Iridium(III) Complexes.
AB  - A homologous family of low-coordinate complexes of the formulation trans-[M(2,2'
      biphenyl)(PR3 )2 ][BArF4 ] (M=Rh, Ir; R=Ph, Cy, iPr, iBu) has been prepared and
      extensively structurally characterised. Enabled through a comprehensive set of
      solution phase (VT 1 H and 31 P NMR spectroscopy) and solid-state (single crystal
      X-ray diffraction) data, and analysis in silico (DFT-based NBO and QTAIM
      analysis), the structural features of the constituent agostic interactions have
      been systematically interrogated. The combined data substantiates the adoption of
      stronger agostic interactions for the IrIII compared to RhIII complexes and, with
      respect to the phosphine ligands, in the order PiBu3 >PCy3 >PiPr3 >PPh3 . In
      addition to these structure-property relationships, the effect of crystal packing
      on the agostic interactions was investigated in the tricyclohexylphosphine
      complexes. Compression of the associated cations, through inclusion of a more
      bulky solvent molecule (1,2-difluorobenzene vs. CH2 Cl2 ) in the lattice or
      collection of data at very low temperature (25 vs. 150 K), lead to small but
      statistically significant shortening of the M-H-C distances.

PMID- 29377309
TI  - Multidisciplinary work in oncology: Population-based analysis for seven invasive
      tumours.
AB  - The concept of multidisciplinary team meetings (MDTs) in cancer care is endorsed
      internationally, but its uptake varies considerably. In Belgium, MDT meetings
      were financially recognised in 2003 to encourage healthcare professionals to join
      their knowledge and competences to improve the quality and coordination of cancer
      care. This study aimed to evaluate for seven cancer types diagnosed between 2004
      and 2011, the practices of MDT meetings in Belgium by means of population-based
      administrative databases. Results show a clear increase over time in the
      proportion of individual patients discussed at MDT meetings. Although this
      evolution may be partly explained by the legal implementation of several
      financial initiatives to stimulate MDT meetings, it also suggests an increase in
      specialists' awareness of the importance of such meetings. Nevertheless, there is
      still room for improvement, for specific cancer types as well as for certain
      subgroups such as older patients. From the specialists' point of view, reducing
      the administrative burden and time these meetings demand may entail a greater
      participation to MDT meetings. Further research is needed to identify the
      barriers to discuss more patients at MDT meetings and to elucidate the impact of
      MDT meetings on the quality of cancer care.

PMID- 29377312
TI  - Task experience influences coordinative structures and performance variables in
      learning a slalom ski-simulator task.
AB  - The experiment investigated the progressions of the qualitative and quantitative
      changes in the movement dynamics of learning the ski-simulator as a function of
      prior-related task experience. The focus was the differential timescales of
      change in the candidate collective variable, neuromuscular synergies, joint
      motions, and task outcome as a function of learning over 7 days of practice. Half
      of the novice participants revealed in day 1 a transition of in-phase to anti
      phase coupling of center of mass (CoM)-platform motion whereas the remaining
      novices and experienced group all produced on the first trial an anti-phase CoM
      platform coupling. The experienced group also had initially greater amplitude and
      velocity of platform motion-a performance advantage over the novice group that
      was reduced but not eliminated with 7 days of practice. The novice participants
      who had an in-phase CoM-platform coupling on the initial trials of day 1 also
      showed the most restricted platform motion in those trials. Prior-related
      practice experience differentially influenced the learning of the task as
      evidenced by both the qualitative organization and the quantitative motion
      properties of the individual degrees of freedom (dof) to meet the task demands.
      The findings provide further evidence to the proposition that CoM-platform
      coupling is a candidate collective variable in the ski-simulator task that
      provides organization and boundary conditions to the motions of the individual
      joint dof and their couplings.

PMID- 29377310
TI  - Nuclear lipid mediators: Role of nuclear sphingolipids and sphingosine-1
      phosphate signaling in epigenetic regulation of inflammation and gene expression.
AB  - Phospholipids, sphingolipids, and cholesterol are integral components of
      eukaryotic cell organelles, including the nucleus. Recent evidence shows
      characteristic features of nuclear lipid composition and signaling, which are
      distinct from that of the cytoplasm and plasma membrane. While the nuclear
      phosphoinositol lipid signaling in cell cycle regulation and differentiation has
      been well described, there is a paucity on the role of nuclear sphingolipids and
      sphingolipid signaling in different physiological and pathophysiological human
      conditions. In this prospective, we describe the role of sphingolipids and
      specifically focus on the sphingoid bases, such as sphingosine, ceramide, and
      sphingosine-1-phosphate (S1P) generation and catabolism in nuclear signaling and
      function. Particularly, S1P generated in the nucleus by phosphorylation of SPHK2
      modulates HDAC activity either by direct binding or through activation of nuclear
      reactive oxygen species and regulates cell cycle and pro-inflammatory gene
      expression. Potential implication of association of SPHK2 with the co-repressor
      complexes and generation of S1P in the nucleus on chromatin remodeling under
      normal and pathological conditions is discussed. A better understanding of
      sphingolipid signaling in the nucleus will facilitate the design and development
      of new and novel therapeutic approaches to modulate expression of pro
      inflammatory and cell cycle dependent genes in human pathologies such as cancer,
      bacterial lung infection, neurodegeneration, and cystic fibrosis.

PMID- 29377314
TI  - Chronology of regional lymph node metastases in cutaneous melanoma: a model based
      on mitotic rate.

PMID- 29377313
TI  - SOST/Sclerostin Improves Posttraumatic Osteoarthritis and Inhibits MMP2/3
      Expression After Injury.
AB  - Patients with anterior cruciate ligament (ACL) rupture are two times as likely to
      develop posttraumatic osteoarthritis (PTOA). Annually, there are ~900,000 knee
      injuries in the United States, which account for ~12% of all osteoarthritis (OA)
      cases. PTOA leads to reduced physical activity, deconditioning of the
      musculoskeletal system, and in severe cases requires joint replacement to restore
      function. Therefore, treatments that would prevent cartilage degradation post
      injury would provide attractive alternatives to surgery. Sclerostin (Sost), a Wnt
      antagonist and a potent negative regulator of bone formation, has recently been
      implicated in regulating chondrocyte function in OA. To determine whether
      elevated levels of Sost play a protective role in PTOA, we examined the
      progression of OA using a noninvasive tibial compression overload model in SOST
      transgenic (SOSTTG ) and knockout (Sost-/- ) mice. Here we report that SOSTTG
      mice develop moderate OA and display significantly less advanced PTOA phenotype
      at 16 weeks post-injury compared with wild-type (WT) controls and Sost-/- . In
      addition, SOSTTG built ~50% and ~65% less osteophyte volume than WT and Sost-/- ,
      respectively. Quantification of metalloproteinase (MMP) activity showed that
      SOSTTG had ~2-fold less MMP activation than WT or Sost-/- , and this was
      supported by a significant reduction in MMP2/3 protein levels, suggesting that
      elevated levels of SOST inhibit the activity of proteolytic enzymes known to
      degrade articular cartilage matrix. Furthermore, intra-articular administration
      of recombinant Sost protein, immediately post-injury, also significantly
      decreased MMP activity levels relative to PBS-treated controls, and Sost
      activation in response to injury was TNFalpha and NF-kappaB dependent. These
      results provide in vivo evidence that sclerostin functions as a protective
      molecule immediately after joint injury to prevent cartilage degradation. (c)
      2018 The Authors. Journal of Bone and Mineral Research Published by Wiley
      Periodicals Inc.

PMID- 29377315
TI  - The Data Hustle: How Beneficiaries Benefit from Continual Data Collection and
      Humanitarian Aid Research in the Somali Region of Ethiopia.
AB  - Based on ethnographic and policy research in the Somali Region of Ethiopia, this
      article examines how contemporary trends in the humanitarian relief industry to
      mandate continual data collection, "accountability," and the "localization" of
      aid have increased demands for participatory and intensive research methodologies
      in crisis-affected communities. International humanitarian relief agencies hustle
      to hire local staffs and recruit enough participants for their repeated research
      projects, while at the same time, the so-called beneficiaries of aid also hustle
      to participate in data collection as paid informants and temporary employees.
      Research is an important side gig for many beneficiaries, and beneficiaries'
      regular participation is vital to reforming humanitarian practice. Beneficiaries
      are not therefore passive recipients of charity, but actively help produce the
      representations of crisis and suffering that, in turn, potentially qualify them
      for aid. Their indispensability and activity within contemporary humanitarian
      "audit cultures" therefore present emergent but limited forms of counter
      hegemonic power.

PMID- 29377316
TI  - A utility of model input uncertainty analysis in transferring tobacco control
      related economic evidence to countries with scarce resources: results from the
      EQUIPT study.
AB  - AIMS: To inform the transferability of tobacco control-related economic evidence
      to resource-poor countries. METHODS: We ran a univariate sensitivity analysis on
      a return on investment (ROI) model, the European study on Quantifying Utility of
      Investment in Protection from Tobacco model (EQUIPTMOD), to identify key input
      values to which the ROI estimates were sensitive. The EQUIPTMOD used a Markov
      based state transition model to estimate the ROI of several tobacco control
      interventions in five European countries (England, Germany, Spain, Hungary and
      the Netherlands). Base case ROI estimates were obtained through average values of
      model inputs (throughout the five countries), which were then replaced one at a
      time with country-specific values. Tornado diagrams were used to evaluate the
      significance of sensitivity, defined as a >= 10% difference in ROI estimates from
      the base case estimates. RESULTS: The ROI estimates were sensitive to 18 (of 46)
      input values. Examples of model inputs to which ROI estimates were sensitive
      included: smoking rate, costs of smoking-related diseases (e.g. lung cancer) and
      general population attributes. CONCLUSION: Countries that have limited research
      time and other resources can adapt EQUIPTMOD to their own settings by choosing to
      collect data on a small number of model inputs. EQUIPTMOD can therefore
      facilitate transfer of tobacco control related economic evidence to new
      jurisdictions.

PMID- 29377317
TI  - A turning point: Head and neck cancer patients' exercise preferences and barriers
      before and after participation in an exercise intervention.
AB  - This study examined the exercise barriers and preferences of head and neck cancer
      (HNC) survivors in relation to exercise experience. Participants (n = 22; 46.8%
      response rate) completed retrospective self-report questionnaires on demographic
      and medical information, exercise barriers and preferences. A subset of
      participants then completed semi-structured interviews (n = 18). Participants had
      previously engaged in the ENHANCE trial during, or immediately following,
      radiation treatment, an average of 22.1 +/- 5.8 months before. Retrospective
      questionnaires revealed that before ENHANCE participation, lack of interest and
      time were the primary exercise barriers. After participation, there was a
      significant decrease in typical barriers including lack of interest (p = .008),
      exercise not a priority (p = .039) and exercise not in routine (p = .004). Number
      of barriers experienced after ENHANCE participation was negatively correlated
      with age, quality of life and minutes of resistance exercise training per week.
      After ENHANCE participation, significant increases were found in preference for
      exercising at a cancer centre (p = .031) and with other cancer survivors (p =
      .016). Four higher order themes emerged inductively from interview data analysis
      pertaining to preferences (i.e., class format) and three higher order themes
      regarding barriers (physical, psychological and external). By investigating
      participants' perspectives after ENHANCE participation, key factors for effective
      HNC exercise programme design were identified.

PMID- 29377318
TI  - Trans-carotid access for TAVR allows safe and rapid exchange for bailout valve-in
      valve procedures.
AB  - Trans-carotid access for trans-catheter aortic valve replacement is a valid
      alternative in patients with aortic valve dysfunction, severe peripheral vascular
      disease, and high-risk for surgery. However, in the event of the need for a
      bailout valve-in-valve procedure, the safety of this access site is uncertain. We
      report a patient with aortic regurgitation, previous coronary surgery, peripheral
      vascular disease, and impaired ventricular function who underwent a CoreValve
      Evolut-R (Medtronic Inc, Minneapolis, MN) implantation through the left carotid
      artery followed by a successful valve-in-valve procedure with a 26-mm Edwards
      Sapien3 valve (Edwards Lifesciences, Irvine, CA) through the same carotid access
      site.

PMID- 29377319
TI  - Comparison of Flexural Strength of Different CAD/CAM PMMA-Based Polymers.
AB  - PURPOSE: To compare the flexural strength of different computer-aided
      design/computer-aided manufacturing (CAD/CAM) poly(methyl methacrylate)-based
      (PMMA) polymers and conventional interim resin materials after thermocycling.
      MATERIALS AND METHODS: Rectangular-shaped specimens (n = 15, for each material)
      (25 * 2 * 2 mm3 ) were fabricated from 3 CAD/CAM PMMA-based polymers (Telio CAD
      [T]; M-PM-Disc [M]; Polident-PMMA [P]), 1 bis-acrylate composite resin (Protemp 4
      [PT]), and 1 conventional PMMA (ArtConcept Artegral Dentine [C]) according to ISO
      10477:2004 Standards (Dentistry-Polymer-Based Crown and Bridge Materials). The
      specimens were subjected to 10,000 thermocycles (5 to 55 degrees C). Three-point
      flexural strength of the specimens was tested in a universal testing machine at a
      1.0 mm/min crosshead speed, and the flexural strength data (sigma) were
      calculated (MPa). The flexural strength values were statistically analyzed using
      1-way ANOVA, and Tukey HSD post-hoc test for multiple comparisons (alpha = 0.05).
      RESULTS: Flexural strength values ranged between 66.1 +/- 13.1 and 131.9 +/- 19.8
      MPa. There were significant differences among the flexural strengths of tested
      materials, except for between T and P CAD/CAM PMMA-based polymers (p > 0.05).
      CAD/CAM PMMA-based polymer M had the highest flexural strength and conventional
      PMMA had the lowest (p < 0.05). CAD/CAM PMMA-based T and P polymers had
      significantly higher flexural strength than the bis-acrylate composite resin (p <
      0.05), and conventional PMMA (p < 0.0001), and significantly lower flexural
      strength compared to CAD/CAM PMMA-based M (p < 0.05). CONCLUSIONS: The flexural
      strength of CAD/CAM PMMA-based polymers was greater than the flexural strength of
      bis-acrylate composite resin, which had a greater flexural strength compared to
      conventional PMMA resin.

PMID- 29377320
TI  - Assessing the economic value of maintained improvements in Type 1 diabetes
      management, in terms of HbA1c , weight and hypoglycaemic event incidence.
AB  - AIMS: Insulin therapy is indicated for people with Type 1 diabetes mellitus;
      however, treatment-related weight gain and hypoglycaemia represent barriers to
      optimal glycaemic management. This study assessed the health economic value of
      maintained reductions in HbA1c , BMI and hypoglycaemia incidence among the UK
      Type 1 diabetes population. METHODS: The Cardiff Type 1 Diabetes Model was used
      to estimate lifetime costs, life-years and quality-adjusted life-years (QALYs)
      for individuals with Type 1 diabetes at different baseline HbA1c , BMI and
      hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary
      benefit associated with improving Type 1 diabetes management was derived at L20
      000/QALY gained. Per-person outputs were inflated to national levels using UK
      Type 1 diabetes prevalence estimates. RESULTS: Modelled subjects with an HbA1c of
      86 mmol/mol (10.0%) were associated with discounted lifetime per-person costs of
      L23 795; L12 649 of which may be avoided by maintaining an HbA1c of 42 mmol/mol
      (6.0%). Combined with estimated QALY gains of 2.80, an HbA1c of 42 mmol/mol
      (6.0%) vs. 86 mmol/mol (10.0%) was associated with a L68 621 per-person net
      monetary benefit. Over 1 year, unit reductions in BMI produced L120 per-person
      net monetary benefit, and up to L197 for the avoidance of one non-severe
      hypoglyceamic event. CONCLUSIONS: Maintained reductions in HbA1c significantly
      alleviate the burden associated with Type 1 diabetes in the UK. Given the
      influence of weight and hypoglycaemia on health economic outcomes, they must also
      be key considerations when assessing the value of Type 1 diabetes technologies in
      clinical practice.

PMID- 29377321
TI  - Small rubber particle proteins from Taraxacum brevicorniculatum promote stress
      tolerance and influence the size and distribution of lipid droplets and
      artificial poly(cis-1,4-isoprene) bodies.
AB  - Natural rubber biosynthesis occurs on rubber particles, i.e. organelles
      resembling small lipid droplets localized in the laticifers of latex-containing
      plant species, such as Hevea brasiliensis and Taraxacum brevicorniculatum. The
      latter expresses five small rubber particle protein (SRPP) isoforms named TbSRPP1
      5, the most abundant proteins in rubber particles. These proteins maintain
      particle stability and are therefore necessary for rubber biosynthesis. TbSRPP1-5
      were transiently expressed in Nicotiana benthamiana protoplasts and the proteins
      were found to be localized on lipid droplets and in the endoplasmic reticulum,
      with TbSRPP1 and TbSRPP3 also present in the cytosol. Bimolecular fluorescence
      complementation confirmed pairwise interactions between all proteins except
      TbSRPP2. The corresponding genes showed diverse expression profiles in young T.
      brevicorniculatum plants exposed to abiotic stress, and all except TbSRPP4 and
      TbSRPP5 were upregulated. Young Arabidopsis thaliana plants that overexpressed
      TbSRPP2 and TbSRPP3 tolerated drought stress better than wild-type plants.
      Furthermore, we used rubber particle extracts and standards to investigate the
      affinity of the TbSRPPs for different phospholipids, revealing a preference for
      negatively charged head groups and 18:2/16:0 fatty acid chains. This finding may
      explain the effect of TbSRPP3-5 on the dispersity of artificial poly(cis-1,4
      isoprene) bodies and on the lipid droplet distribution we observed in N.
      benthamiana leaves. Our data provide insight into the assembly of TbSRPPs on
      rubber particles, their role in rubber particle structure, and the link between
      rubber biosynthesis and lipid droplet-associated stress responses, suggesting
      that SRPPs form the basis of evolutionarily conserved intracellular complexes in
      plants.

PMID- 29377322
TI  - Shared and distinct alterations of white matter tracts in remitted and
      nonremitted patients with schizophrenia.
AB  - Patients with schizophrenia do not usually achieve remission state even after
      adequate antipsychotics treatment. Previous studies found significant difference
      in white matter integrity between patients with good outcomes and those with poor
      outcomes, but difference is still unclear at individual tract level. This study
      aimed to use a systematic approach to identify the tracts that were associated
      with remission state in patients with schizophrenia. We evaluated 91 patients
      with schizophrenia (remitted, 50; nonremitted, 41) and 50 healthy controls
      through diffusion spectrum imaging. White matter tract integrity was assessed
      through an automatic tract-specific analysis method to determine the mean
      generalized fractional anisotropy (GFA) values of the 76 white matter tract
      bundles in each participant. Analysis of covariance among the 3 groups revealed
      12 tracts that were significantly different in GFA values. Post-hoc analysis
      showed that compared with the healthy controls, the nonremission group had
      reduced integrity in all 12 tracts, whereas the remission group had reduced
      integrity in only 4 tracts. Comparison between the remission and nonremission
      groups revealed 4 tracts with significant difference (i.e., the right fornix,
      bilateral uncinate fasciculi, and callosal fibers connecting the temporal poles)
      even after adjusting age, sex, education year, illness duration, and medication
      dose. Furthermore, all the 4 tracts were correlated with negative symptoms scores
      of the positive and negative syndrome scale. In conclusion, our study identified
      the tracts that were associated with remission state of schizophrenia. These
      tracts might be a potential prognostic marker for the symptomatic remission in
      patients with schizophrenia.

PMID- 29377324
TI  - Differences in Prevalence of Muscle Weakness (Sarcopenia) in Haemodialysis
      Patients Determined by Hand Grip Strength Due to Variation in Guideline
      Definitions of Sarcopenia.
AB  - BACKGROUND: Muscle weakness is associated with increased mortality, and
      hemodialysis (HD) patients are at an increased risk for muscle loss. There is no
      agreed definition for muscle weakness, so we determined whether using different
      cut-off criteria recommended by guideline groups altered the prevalence in HD
      patients. METHODS: We measured hand grip strength (HGS) in HD outpatients,
      comparing HGS with clinical guideline cut-offs (European Working Group on
      Sarcopenia in Older People [EWGSOP] and North American Foundation for the
      National Institutes of Health Sarcopenia Project [FNIH]) used to define muscle
      wasting (sarcopenia) with age-matched and gender-matched normative data. RESULTS:
      We studied 459 patients, 61.4% male, 47.3% diabetic. The prevalence of muscle
      weakness was significantly different when measuring HGS; 84.5% using the EWGSOP
      cut-off and 73.2% with FNIH criteria, and 75.2% using North American normative
      data and 56.6% U.K. normative data (P < .01). On logistic regression, muscle
      weakness was associated with age (odds ratio [OR] 1.05, P < .001), weight (OR
      0.96, P < .001), serum albumin (OR 0.89, P = .007), and being nondiabetic (OR
      0.31, P = .001). Of patients with no comorbidity, 66.7% were weak when compared
      with 93.8% with the highest comorbidity scores (P < .001). CONCLUSION: There is
      currently no agreed universal definition for sarcopenia, but the EWGSOP and FNIH
      advocate HGS cut-offs as part of their definition. The prevalence of muscle
      weakness varies according to cut-off and whether age-matched and gender-matched
      normative data are used. In addition, patient characteristics in terms of age and
      comorbidity determine the prevalence of muscle weakness.

PMID- 29377325
TI  - Correspondence regarding the impact of kidney transplantation on insulin
      sensitivity.

PMID- 29377326
TI  - A Study on Possibility of Clinical Application for Color Measurements of Shade
      Guides Using an Intraoral Digital Scanner.
AB  - PURPOSE: To assess if color measurement with intraoral scanner correlates with
      digital colorimeter and to evaluate the possibility of application of a digital
      scanner for shade selection. MATERIALS AND METHODS: The L*a*b* values of the five
      shade tabs (A1, A2, A3, A3.5, and A4) were obtained with an intraoral scanner
      (TRIOS Pod) and a colorimeter (ShadeEye). Both devices were calibrated according
      to the manufacturer's instructions before measurements. Color measurement values
      were compared with paired t-test, and a Pearson's correlation analysis was
      performed to evaluate the relationship of two methods. RESULTS: The L*a*b* values
      of the colorimeter were significantly different from those of the digital scanner
      (p < 0.001). The L* and b* values of both methods were strongly correlated with
      each other (both p < 0.05). The device repeatability in both methods were
      reported to be excellent (p < 0.05). Within the limitations of this study, color
      measurements with digital intraoral scanners and computer-assisted image analysis
      were in accordance with those of the colorimeter with respect to L* and b*
      values; however, all the coordinates of shade tabs were significantly different
      between two methods. CONCLUSIONS: The digital intraoral scanner may not be used
      as the primary method of color selection in clinical practices, considering
      significant differences in color parameters with colorimeter. The scanner's
      capability in shade selection should be further evaluated.

PMID- 29377327
TI  - Comprehensive circRNA expression profile and construction of circRNA-associated
      ceRNA network in fur skin.
AB  - Circular RNA (circRNA), a class of non-coding RNAs, is a new group of RNAs that
      are related to tumorigenesis. The role of circRNAs in various diseases has been
      already highlighted. However, the expression levels and functions of circRNAs
      related to the melanocytes in the skin are poorly understood. RNA sequence was
      performed to analyse the expression profiles of circRNAs in black fur skin and
      white fur skin during different differentiation stages and investigate the
      relevant metabolism mechanisms. Differentially expressed circRNAs were detected
      using empirical Bayes sequencing (EBSeq) and then verified through the
      quantitative real-time PCR method. The EQSeq analysis of circRNAs identified 11
      downregulated and 32 upregulated circRNAs in the embryo of black fur skin and
      white fur skin, as well as 21 downregulated and 17 upregulated circRNA in the
      postnatal stage. A circRNA-microRNA (miRNA)-messenger RNA (mRNA) network was
      established to predict the circRNA targets. Gene ontology (GO) analysis and Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway analysis were applied to enrich
      the mRNA data further. Results showed that the specific mRNAs mainly involved in
      the transcription-related GOs, especially GO:0042802, GO:0005080 and GO:0032403,
      demonstrate their specific actions in transcriptional regulation. In the circRNA
      miRNA-mRNA network, the most enriched GO terms of the mRNAs were pigmentation,
      protein autophosphorylation and protein complex. Therefore, the circRNA-miRNA
      mRNA pathway may reveal novel mechanisms for pigmentation, and circRNAs may serve
      as candidates in pigmentation.

PMID- 29377328
TI  - Nitrergic signaling via interstitial cells of Cajal and smooth muscle cells
      influences circular smooth muscle contractility in murine colon.
AB  - BACKGROUND: Regulation of gastrointestinal motility involves excitatory and
      inhibitory neurotransmission. Nitric oxide (NO), the major inhibitory
      neurotransmitter, acts via its receptor NO-sensitive guanylyl cyclase (NO-GC). In
      the GI tract, NO-GC is expressed in several cell types such as smooth muscle
      cells (SMC) and interstitial cells of Cajal (ICC). Using cell-specific knockout
      mice, we have previously shown that NO-GC modulates spontaneous contractions in
      colonic longitudinal smooth muscle. However, its detailed role in the colonic
      circular smooth muscle is still unclear. METHODS: Myography was performed to
      evaluate spontaneous contractions in rings of proximal colon (2.5 mm) from global
      (GCKO) and cell-specific knockout mice for NO-GC. Immunohistochemistry and in
      situ hybridization were used to specify NO-GC expression. KEY RESULTS: Colonic
      circular smooth muscle showed three different contraction patterns: high
      frequency ripples, slow phasic contractions, and large contractions. Ripples
      formed independently of NO-GC. Slow phasic contractions occurred intermittently
      in WT, SMC-GCKO, and ICC-GCKO tissue, whereas they were more prominent and
      prolonged in GCKO and SMC/ICC-GCKO tissue. Tetrodotoxin and the NO-GC inhibitor
      ODQ transformed slow phasic contractions of WT and single cell-specific knockout
      into GCKO-like contractions. ODQ increased the frequency of large contractions in
      WT and ICC-GCKO colon but not in GCKO, SMC-GCKO, and SMC/ICC-GCKO preparations.
      Tetrodotoxin and hexamethonium abolished large contractions. CONCLUSIONS AND
      INFERENCES: We conclude that short rings of murine colon can be effectively used
      to record spontaneous contractions. Although NO-GC in SMC determines smooth
      muscle tone, concerted action of NO-GC in both SMC and ICC modulates slow phasic
      contractions and large contractions.

PMID- 29377329
TI  - Efficient production and characterization of homopolymeric poly(3
      hydroxyvalerate) produced by Bacillus strain PJC48.
AB  - Aliphatic polyester, poly(3-hydroxyvalerate) (PHV), is commonly produced as a
      granular component in bacterial cells of various species. Based on 16S rDNA gene
      sequence analysis, strain PJC48 was identified as a Bacillus species. The current
      study is aimed to screen for a high-yield strain that can produce PHV efficiently
      and to increase PHV product yield by optimizing the fermentative process. We
      identified a high-producer strain based on Nile red staining. Characterization of
      the PHV produced by PJC48 by nuclear magnetic resonance spectroscopy revealed
      that it consisted of (R)-3-hydroxyvalerate monomers. The suggested model was
      validated by response surface methodology. Optimization of the PHV yield resulted
      in an increase of 32.75% compared to control, with a maximum production of 1.64
      g/L after 48 H.

PMID- 29377330
TI  - The poly-cistronic expression of four transcriptional factors (CRX, RAX, NEURO-D,
      OTX2) in fibroblasts via retro- or lentivirus causes partial reprogramming into
      photoreceptor cells.
AB  - The introduction of four key transcriptional factors (CRX, RAX, NEURO-D, OTX2)
      allows the direct differentiation of fibroblasts to retinal photoreceptor cells.
      This reprogramming was achieved with a combination of mono-cistronic viruses.
      Although the combination of mono-cistronic viruses was useful, a relatively high
      titer of recombinant viruses was necessary because co-infections are required. To
      overcome this issue, we established a poly-cistronic expression system for direct
      reprogramming and analyzed the biological characteristics of introduced cells
      after the exogenous introduction. The coding region of four reprogramming factors
      and EGFP (CRX, RAX, NEURO-D, OTX2, and EGFP; CNROE) was inserted into multiple
      sites of the pMYs-IP retrovirus or CSII-CMV lentivirus vector. The recombinant
      viruses were exposed to HE16 human embryonic fibroblasts. The expression levels
      of cone related genes were detected with real-time PCR. We detected the
      activation of two of the photoreceptor-related genes after the poly-cistronic
      expression of CRX, RAX, NEURO-D, and OTX2, but the rest of the genes did not
      exhibit transcriptional elevation. We concluded that the poly-cistronic
      expression of CNROE induced partial reprogramming into photoreceptor cells. We
      hypothesize that the direct reprogramming into photoreceptor cells might require
      relatively high protein expression levels of transcriptional factors.

PMID- 29377331
TI  - C-C Bond Formation of Mg- and Zn-Activated Carbon Dioxide.
AB  - Gas-phase activation of CO2 by chloride tagged metal atoms, [ClM]- (M=Mg, Zn),
      has been investigated by mass spectrometry and high-level quantum chemistry. Both
      metals activate CO2 with significant bending of the CO2 moiety to form complexes
      with the general formula [ClM,CO2 ]- . The structure of the metal-CO2 complex
      depends on the method of formation, and the energy landscapes and reaction
      dynamics have been probed by collisional induced dissociation and thermal ion
      molecule reactions with isotopically labeled species. Having established these
      structural relationships, the gas-phase reactivity of [ClM(kappa2 -O2 C)]- with
      acetaldehyde (here considered a carbohydrate mimic) was then studied. Formation
      of lactate and enolate-pyruvate complexes are observed, showing that CO2 fixation
      by C-C bond formation takes place. For M=Zn, even formation of free pyruvate ([C3
      H3 O3 ]- ) is observed. Implications of the observed CO2 reactivity for the
      electrochemical conversion of carbon dioxide, and to biochemical and artificial
      photosynthesis is briefly discussed. Detailed potential energy diagrams obtained
      by the quantum chemical calculations offer models consistent with experimental
      observation.

PMID- 29377332
TI  - Resemblance of a model species and its mimic: Reply to Valkonen and Mappes 2014.

PMID- 29377333
TI  - Permissive or Trophic Enteral Nutrition and Full Enteral Nutrition Had Similar
      Effects on Clinical Outcomes in Intensive Care: A Systematic Review of Randomized
      Clinical Trials.
AB  - The aim of this study was to systematically review the effect of permissive
      underfeeding/trophic feeding on the clinical outcomes of critically ill patients.
      A systematic review of randomized clinical trials to evaluate the mortality,
      length of stay, and mechanical ventilation duration in patients randomized to
      either hypocaloric or full-energy enteral nutrition was performed. Data sources
      included PubMed and Scopus and the reference lists of the articles retrieved. Two
      independent reviewers participated in all phases of this systematic review as
      proposed by the Cochrane Handbook, and the review was reported according to
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A
      total of 7 randomized clinical trials that included a total of 1,717 patients
      were reviewed. Intensive care unit length of stay and mechanical ventilation
      duration were not statistically different between the intervention and control
      groups in all randomized clinical trials, and mortality rate was also not
      different between the groups. In conclusion, hypocaloric enteral nutrition had no
      significantly different effects on morbidity and mortality in critically ill
      patients when compared with full-energy nutrition. It is still necessary to
      determine the safety of this intervention in this group of patients, the optimal
      amount of energy provided, and the duration of this therapy.

PMID- 29377334
TI  - Effect of finish line design on stress distribution in bilayer and monolithic
      zirconia crowns: a three-dimensional finite element analysis study.
AB  - This study evaluated the influence of different finish line designs and abutment
      materials on the stress distribution of bilayer and monolithic zirconia crowns
      using three-dimensional finite element analysis (FEA). Three-dimensional models
      of two types of zirconia premolars - a yttria-stabilized zirconia framework with
      veneering ceramic and a monolithic zirconia ceramic - were used in the analysis.
      Cylindrical models with the finish line design of the crown abutments were
      prepared with three types of margin curvature radius (CR): CR = 0 (CR0; shoulder
      margin), CR = 0.5 (CR0.5; rounded shoulder margin), and CR = 1.0 (CR1.0; deep
      chamfer margin). Two abutment materials (dentin and brass) were analyzed. In the
      FEA model, 1 N was loaded perpendicular to the occlusal surface at the center of
      the crown, and linear static analysis was performed. For all crowns, stress was
      localized to the occlusal loading area as well as to the axial walls of the
      proximal region. The lowest maximum principal stress values were observed when
      the dentin abutment with CR0.5 was used under a monolithic zirconia crown. These
      results suggest that the rounded shoulder margin and deep chamfer margin, in
      combination with a monolithic zirconia crown, potentially have optimal geometry
      to minimize occlusal stress.

PMID- 29377335
TI  - Being mindful of mindfulness interventions in cancer: A systematic review of
      intervention reporting and study methodology.
AB  - OBJECTIVES: While mindfulness-based stress reduction (MBSR) and mindfulness-based
      cognitive therapy (MBCT) have demonstrated efficacy in clinical populations, the
      potential therapeutic benefit of mindfulness in the context of cancer is less
      clear. The aim of this review was to critically appraise mindfulness intervention
      reporting and study methodology. METHODS: Studies using randomized control trial
      design and/or a control arm were included. PubMed, Medline, PsycINFO, CINAHL, and
      Embase databases between January 1999 and April 2017 were searched. Studies were
      assessed on (1) reported theoretical framework, (2) intervention description, and
      (3) justification of modifications to standardized MBSR/MBCT. The overall quality
      of study design and research methodology were also assessed. RESULTS: Of 30
      studies identified, none adhered to MBSR. Modified versions of MBSR were reported
      in 19 studies. Five studies reported variants of MBCT, 1 used a combination of
      MBSR/MBCT, and 5 inadequately documented the intervention/ theoretical framework.
      Overall, component and timeline modifications were poorly documented and
      justified. Mean intervention contact time was less than standardized MBSR/MBCT
      protocols. Target outcomes were poorly justified, and 12 studies failed to
      identify a primary aim, reporting multiple outcomes. Only 9 of 15 studies
      recruiting clinical populations included clinical cutoffs, and an active
      therapeutic control was included in 4 studies. CONCLUSIONS: Mindfulness is
      increasingly considered a standard therapy in psycho-oncology. While many studies
      proclaim benefits, considerable variability, modification to standardized
      protocols, and claims of benefit often reflect decreases in sub-clinical
      supportive care symptomology rather than therapeutic relief of clinically
      significant psychological disorders.

PMID- 29377336
TI  - Handheld 3-dimensional wound measuring system.
AB  - BACKGROUND: Measuring wound dimensions is important for monitoring and predicting
      the healing process. In our paper we propose and validate a handheld measuring
      system with dedicated software for measuring wound dimensions. METHODS: The
      measuring system comprises a commercial DSLR camera and a light pattern
      projection system. It is based on triangulation and structured illumination
      principles which enable handheld measuring. An edge of the wound is detected from
      the colour information of the measurement. Across the area of the wound, virtual
      healthy skin is approximated which enables the calculation of the wound volume
      and area, in addition to the wound circumference, which is calculated from the
      detected edge. RESULTS: In vitro verification using virtual standards showed that
      the accuracy of the analysis software is over 95% and 93% for measuring the area
      and volume respectively. A significant part of the error can be attributed to the
      inability of approximation to replicate entirely missing features. The accuracy
      of measuring the volume reduced to about 89% when a 3D measuring step was
      included in the analysis. When measuring in vivo wounds, the unrepeatability of
      the system was under 8% for measuring the area, which is a bit lower than
      comparable systems, and 5% for measuring the volume, which is about 4 times
      lower. CONCLUSION: Based on these results and the ease of use, we conclude that
      the system is suitable to be used in daily clinical practice for measuring wound
      dimensions.

PMID- 29377337
TI  - Landscape consequences of aggregation rules for functional equivalence in
      compensatory mitigation programs.
AB  - Mitigation and offset programs designed to compensate for ecosystem function
      losses due to development must balance losses from affected ecosystems with gains
      in restored ecosystems. Aggregation rules applied to ecosystem functions to
      assess site equivalence are based on implicit assumptions about the
      substitutability of functions among sites and can profoundly influence the
      distribution of restored ecosystem functions on the landscape. We investigated
      the consequences of rules applied to the aggregation of ecosystem functions for
      wetland offsets in the Beaverhill watershed in Alberta, Canada. We considered the
      fate of 3 ecosystem functions: hydrology, water purification, and biodiversity.
      We set up an affect-and-offset algorithm to simulate the effect of aggregation
      rules on ecosystem function for wetland offsets. Cobenefits and trade-offs among
      functions and the constraints posed by the quantity and quality of restorable
      sites resulted in a redistribution of functions between affected and offset
      wetlands. Hydrology and water purification functions were positively correlated
      with one another and negatively correlated with biodiversity function. Weighted
      average rules did not replace functions in proportion to their weights. Rules
      prioritizing biodiversity function led to more monofunctional wetlands and
      landscapes. The minimum rule, for which the wetland score was equal to the worst
      performing function, promoted multifunctional wetlands and landscapes. The
      maximum rule, for which the wetland score was equal to the best performing
      function, promoted monofunctional wetlands and multifunctional landscapes.
      Because of implicit trade-offs among ecosystem functions, no-net-loss objectives
      for multiple functions should be constructed within a landscape context. Based on
      our results, we suggest criteria for the design of aggregation rules for no net
      loss of ecosystem functions within a landscape context include the concepts of
      substitutability, cobenefits and trade-offs, landscape constraints,
      heterogeneity, and the precautionary principle.

PMID- 29377338
TI  - Clinical Effectiveness of 6.5-mm-Long Implants to Support Two-Implant Fixed
      Prostheses in Premolar-Molar Region: The Influence of Immediate Loading and the
      Length of Splinting Implant.
AB  - PURPOSE: The purpose of this retrospective clinical study was to assess the
      influence of immediate loading and lengths of splinted implants on the clinical
      effectiveness of 6.5-mm-long implants supporting two-implant fixed prostheses in
      the premolar-molar regions. MATERIALS AND METHODS: A clinical database was
      reviewed in a private dental center to select those patients who had 6.5-mm-long
      implants placed to support two-implant fixed partial prostheses in the premolar
      molar regions of the maxilla and the mandible. All implants were immediately
      loaded. The study groups were defined according to the lengths of the implants.
      Two groups were identified: the short-short splinted group, when both implants
      had 6.5 mm lengths, and the short-long splinted group, when one implant was
      longer than 6.5 mm. A total of 48 dental implants were placed in 16 patients to
      support 24 two-implant fixed prostheses. The mean follow-up time was 14 +/- 5
      months. The short-short splinted group included 8 patients with 16 implants; the
      short-long splinted group included 16 patients with 32 implants. The main
      variable was implant survival, and secondary outcomes were marginal bone
      stability and prosthesis survival. RESULTS: The statistical analyses indicated an
      absence of significant differences between the two groups in terms of implant and
      prosthesis survival (100% for both groups and both variables); however, distal
      bone loss around the splinted implants was significantly higher in the short-long
      splinted group. Bone loss was 0.37 +/- 0.55 mm in the short-short splinted group
      and 0.94 +/- 0.66 mm in the short-long splinted group. CONCLUSIONS: Immediate
      loading of short (6.5-mm-long) implants in the premolar-molar regions did not
      jeopardize their survival. Two-implant supported prostheses had the same clinical
      effectiveness, whether extra-short implants were splinted to another extra-short
      implant or to a longer one.

PMID- 29377339
TI  - Antiproliferation of keratinocytes and alleviation of psoriasis by the ethanol
      extract of Artemisia capillaris.
AB  - The therapeutic potentials of the ethanol extract of Artemisia capillaris (ACE)
      for psoriasis were verified in HaCaT cells (as an immortalized human keratinocyte
      cell line) and imiquimod (IMQ)-induced psoriasis-like mouse models. In HaCaT
      cells, IC50 value of ACE was 37.5 MUg/ml after incubating for 72 hr. The
      antiproliferation activity of ACE in HaCaT cells was further verified by
      apoptosis assays. The percentage of apoptotic population in ACE-treated group was
      significantly higher than that of control group (p < .05). The result of cell
      cycle arrest assay also supported the observed antiproliferation efficacy of ACE
      in HaCaT cells. In IMQ-induced psoriasis-like mouse models, the Psoriasis Area
      and Severity Index score of ACE (50 mg/ml; ACE50)-treated group was significantly
      lower than that of IMQ group on Day 4 (p < .05). After topical application of ACE
      on psoriasis-like lesion for 4 days, the epidermal thickness of (IMQ + ACE50)
      group was significantly lower than that of IMQ group (p < .05). The expression
      levels of Ki-67 and intracellular adhesion molecule-1 in excised skin tissues of
      (IMQ + ACE50) group were also lower than those of IMQ group. All these findings
      suggest that ACE can be used as a promising antipsoriatic agent.

PMID- 29377340
TI  - Nuclear pseudoinclusions in melanoma cells: prognostic fact or artifact? The
      possible role of Golgi phosphoprotein 3 overexpression in nuclear
      pseudoinclusions generation.
AB  - Nuclear pseudoinclusions (NPIs) are classically found in papillary thyroid
      carcinoma and meningioma. Although NPIs have been described in melanocytic
      lesions, there is no systematic analysis of potential relationship between NPIs
      and other clinicopathological characteristics of melanoma. We examined the
      presence of NPIs in H&E-stained tissue sections form 96 melanomas and analyzed
      statistical associations with important clinicopathological parameters and tissue
      immunoreactivity for selected proteins involved in epithelial-mesenchymal
      transition (SPARC, N-cadherin), cell adhesion and mobility (ALCAM, ADAM-10),
      regulation of mitosis (PLK1), cell survival (FOXP1) and functioning of Golgi
      apparatus (GOLPH3, GP73). NPIs were observed in 20% of melanomas and their
      presence correlated with high mitotic rate and ulceration of the tumor, but not
      with Breslow thickness, histologic type, or presence of metastases. We observed a
      significant correlation with shorter cancer-specific survival, but not disease
      free survival. Presence of NPIs was related to high expression of GOLPH3 in
      melanoma cells, whereas their absence was linked to enhanced immunoreactivity of
      GOLPH3 in tumor-associated macrophages. NPIs are not an uncommon finding in skin
      melanoma and their diagnostic and prognostic utility could be helpful in the
      daily routine histopathological practice. The possible explanation of NPI
      generation is associated with enhanced activity of Golgi apparatus in melanoma
      cells.

PMID- 29377342
TI  - Merchants of doubt in the free-ranging cat conflict.

PMID- 29377343
TI  - Spinal Cord Stimulation Improves the Microvascular Perfusion Insufficiency Caused
      by Critical Limb Ischemia.
AB  - OBJECTIVE: This retrospective case-controlled study intended to identify the
      benefits and efficacy of spinal cord stimulation (SCS) as a therapeutic strategy
      for patients with perfusion problems caused by critical limb ischemia (CLI). The
      outcomes of patients who received SCS were compared with those of patients who
      did not receive SCS. METHODS: This study recruited 78 patients who were diagnosed
      with perfusion problems over the period of 2003-2011. Lower-limb Thallium-201
      (201 Tl) scintigraphy revealed that the patients exhibited a perfusion difference
      of <0.95. Thirty-seven of the recruited patients received SCS treatment and 41
      did not receive SCS treatment. All patients received the same medication: 100 mg
      aspirin once a day and 500 mg paracetamol thrice a day. The outcomes of walking
      distance, walking time, and sleeping quality were measured and recorded. Pain
      intensities were evaluated using the visual analog scale (VAS) scoring system.
      RESULTS: Prior to SCS implantation, patients in the SCS treatment group had worse
      walking distance (64.86 +/- 40.80 vs. 613.70 +/- 535.00, p < 0.001), walking time
      (2.65 +/- 1.64 vs. 13.90 +/- 11.91, p < 0.001), and sleep quality (1.70 +/- 0.78
      vs. 3.32 +/- 1.17, p < 0.001) than patients in the non-SCS treatment group. At
      the one-year follow-up, however, patients in the SCS treatment group had
      significantly better walking distance (1595.00 +/- 483.60, p < 0.001), walking
      time (48.92 +/- 14.10, p < 0.001), and sleep quality (4.65 +/- 0.92, p < 0.001)
      than patients in the non-SCS treatment group. Moreover, the VAS score of patients
      in the SCS treatment group improved one week (8.63 +/- 0.54 vs. 4.48 +/- 0.59, p
      < 0.001) and one year after SCS implantation (2.35 +/- 0.62, p < 0.001). By
      contrast, at the one-year follow-up, the walking distance (277.60 +/- 374.80, p =
      0.002), walking time (9.44 +/- 10.73, p = 0.078), sleep quality (2.20 +/- 1.10, p
      < 0.001), and VAS score (7.98 +/- 0.43, p = 0.020) of patients in the non-SCS
      treatment group worsened. Furthermore, lower-limb 201 Tl scintigraphy revealed
      that microcirculation intensity increased in the lower extremities of patients in
      the SCS treatment group after SCS implantation relative to that before SCS
      implantation. Most importantly, 10 of the 41 patients in the non-SCS treatment
      group required the use of wheelchairs, whereas none of the patients in the SCS
      treatment group required the use of wheelchairs. CONCLUSION: Treatment of CLI
      patient with SCS improved patient's walking ability, pain severity, and sleep
      quality. SCS should be considered as an effective treatment toward limb salvage
      in CLI.

PMID- 29377341
TI  - The influence of exposome on acne.
AB  - BACKGROUND: Acne vulgaris is one of the main reasons for dermatological
      consultations. Severity and response to treatment may be impacted by various
      external factors or exposome. AIM: To assess the impact of environmental factors
      on acne and to provide a comprehensive overview of the acne exposome. METHODS:
      Two consensus meetings of five European dermatologists and a comprehensive
      literature search on exposome factors triggering acne served as a basis for this
      review. RESULTS: Acne exposome was defined as the sum of all environmental
      factors influencing the occurrence, duration and severity of acne. Exposome
      factors impact on the response and the frequency of relapse to treatments by
      interacting with the skin barrier, sebaceous gland, innate immunity and cutaneous
      microbiota. They may be classified into the following six main categories:
      nutrition, psychological and lifestyle factors, occupational factors including
      cosmetics, as well as pollutants, medication and climatic factors. Moreover,
      practical considerations for the dermatologist's clinical practice are proposed.
      CONCLUSION: Exposome factors including nutrition, medication, occupational
      factors, pollutants, climatic factors, and psychosocial and lifestyle factors may
      impact on the course and severity of acne and on treatment efficacy. Identifying
      and reducing the impact of exposome is important for an adequate acne disease
      management.

PMID- 29377344
TI  - Reversed actinic damage in two children with xeroderma pigmentosum treated with
      topical imiquimod.

PMID- 29377345
TI  - Structural insights into Resolvin D4 actions and further metabolites via a new
      total organic synthesis and validation.
AB  - Local production and downstream metabolism of specialized proresolving lipid
      mediators (SPMs) are pivotal in regulating their biological actions during
      resolution of inflammation. Resolvin D4 (RvD4: 4S,5R,17S-trihydroxydocosa
      6E,8E,10Z,13Z,15E,19Z hexaenoic acid) is one of the more recently elucidated SPMs
      with complete stereochemistry biosynthesized from docosahexaenoic acid . Here, we
      report a new multimilligram commercial synthesis that afforded enough material
      for matching, validation, and further evaluation of RvD4 functions. Using LC-MS
      MS profiling, RvD4 was identified at bioactive amounts in human (1 pg/mL) and
      mouse bone marrow (12 pg/femur and tibia). In mouse bone marrow, ischemia
      increased the formation of RvD4 > 37-fold (455 pg/femur and tibia). Two separate
      mouse ischemic injury models were used, where RvD4 reduced second organ
      reperfusion lung injury > 50%, demonstrating organ protection. Structure-function
      relationships of RvD4 demonstrated > 40% increase in neutrophil and monocyte
      phagocytic function in human whole blood in comparison with 2 separate trans
      containing double bond isomers that were inactive. These 2 isomers were prepared
      by organic synthesis: 4S,5R,17S-trihydroxydocosa-6E,8E,10E,13Z,15E,19Z-hexaenoic
      acid (10-trans-RvD4), a natural isomer, and 4S,5R,17S-trihydroxydocosa
      6E,8E,10E,13E,15E,19Z-hexaenoic acid (10,13-trans-RvD4), a rogue isomer. Compared
      to leukotriene B4 , D-series resolvins (RvD1, RvD2, RvD3, RvD4, or RvD5) did not
      stimulate human neutrophil chemotaxis monitored via real-time microfluidics
      chambers. A novel 17-oxo-containing-RvD4 product of eicosanoid oxidoreductase was
      identified with human bone marrow cells. Comparison of 17-oxo-RvD4 to RvD4
      demonstrated that with human leukocytes 17-oxo-RvD4 was inactive. Together, these
      provide commercial-scale synthesis that permitted a second independent validation
      of RvD4 complete stereochemical structure as well as evidence for RvD4 regulation
      in tissues and its stereoselective phagocyte responses.

PMID- 29377346
TI  - Changes in dermal structure and skin oxidative stress in overweight and obese
      Japanese males after weight loss: a longitudinal observation study.
AB  - BACKGROUND/PURPOSE: Previous studies have reported decreased dermal echogenicity
      and increased skin oxidative stress in overweight males. However, it is unknown
      whether these skin parameters of overweight and obese people are similar to those
      of individuals exhibiting a normal body weight following weight loss. The purpose
      of this study was to (1) compare the changes in the dermal structure parameters
      and levels of skin oxidative stress before and after weight loss in overweight
      and obese people in Japan and (2) to clarify how these aspects changed when body
      weight would be reduced to normal body weight. METHODS: Male volunteers with a
      body mass index of >=25 kg/m2 were recruited. The dermal structure was visualized
      and dermal echogenicity and thickness were measured using ultrasound scanners.
      The mRNA expression level of heme oxygenase-1 in the hair follicles was
      quantitatively analyzed as a marker of skin oxidative stress. RESULTS: When
      overweight individuals in their 20s to 30s reduced their weight to normal,
      decreased dermal thickness in the abdominal region was observed in 50% of the
      subjects; however, no increase in dermal echogenicity was observed. A decrease in
      dermal thickness and an increase in dermal echogenicity in the thighs was
      observed in 83.3% of the subjects. No decrease in the level of dermal oxidative
      stress was observed. CONCLUSION: The dermal structure in the thighs of overweight
      young individuals can be improved to the level of the structure in those of
      normal body weight individuals following weight loss.

PMID- 29377348
TI  - PAI 2018: Passing the baton.

PMID- 29377347
TI  - Tunicamycin inhibits cell proliferation and migration in hepatocellular carcinoma
      through suppression of CD44s and the ERK1/2 pathway.
AB  - Tunicamycin (TM) is an N-linked glycosylation (NLG) inhibitor with strong
      antitumor activity, the exact underlying molecular mechanism of which remains to
      be elucidated. In our previous studies, we found that TM reversed drug resistance
      and improved the efficacy of combination treatments for hepatocellular carcinomas
      (HCC). Here, we investigated the effects of TM on HCC cell proliferation and
      migration as well as the mechanism of those effects. Our results showed that TM
      inhibited cell proliferation and migration as well as induced apoptosis of
      hepatocellular carcinoma cells. TM inhibited proliferation of HCC cells by
      inducing cell apoptosis and cell cycle arrest at the G2/M phase. Meanwhile, TM
      inhibited migration of HCC cells by suppressing CD44s-mediated epithelial
      mesenchymal transition (EMT). TM inhibited migration and invasion of HCC cells by
      decreasing CD44 expression and altering its glycosylation. In addition, CD44s is
      involved in promoting EMT and is associated with a poor prognosis in HCC
      patients. Overexpression of CD44s promoted tumor migration and activated
      phosphorylation of ERK1/2 in HCC cells, whereas TM inhibited CD44s overexpression
      associated cell migration. The ability of TM to inhibit cell migration and
      invasion was enhanced or reversed in CD44s knockdown cells and cells
      overexpressing CD44s, respectively. The MEK/ERK inhibitor U0126 and TM inhibited
      hyaluronic acid-induced cell migration in HCC cells. Furthermore, TM inhibited
      exogenous transforming growth factor beta (TGF-beta)-mediated EMT by an ERK1/2
      dependent mechanism and restored the TGF-beta-mediated loss of E-cadherin. In
      summary, our study provides evidence that TM inhibits proliferation and migration
      of HCC cells through inhibition of CD44s and the ERK1/2 signaling pathway.

PMID- 29377350
TI  - It takes two types of allergists to serve the needs of all allergic patients.

PMID- 29377352
TI  - 3D imaging of cleared human skin biopsies using light-sheet microscopy: A new way
      to visualize in-depth skin structure.
AB  - BACKGROUND: Human skin is composed of the superimposition of tissue layers of
      various thicknesses and components. Histological staining of skin sections is the
      benchmark approach to analyse the organization and integrity of human skin
      biopsies; however, this approach does not allow 3D tissue visualization.
      Alternatively, confocal or two-photon microscopy is an effective approach to
      perform fluorescent-based 3D imaging. However, owing to light scattering, these
      methods display limited light penetration in depth. The objectives of this study
      were therefore to combine optical clearing and light-sheet fluorescence
      microscopy (LSFM) to perform in-depth optical sectioning of 5 mm-thick human skin
      biopsies and generate 3D images of entire human skin biopsies. MATERIALS AND
      METHODS: A benzyl alcohol and benzyl benzoate solution was used to successfully
      optically clear entire formalin fixed human skin biopsies, making them
      transparent. In-depth optical sectioning was performed with LSFM on the basis of
      tissue-autofluorescence observations. 3D image analysis of optical sections
      generated with LSFM was performed by using the Amira(r) software. RESULTS: This
      new approach allowed us to observe in situ the different layers and compartments
      of human skin, such as the stratum corneum, the dermis and epidermal appendages.
      With this approach, we easily performed 3D reconstruction to visualise an entire
      human skin biopsy. Finally, we demonstrated that this method is useful to
      visualise and quantify histological anomalies, such as epidermal hyperplasia.
      CONCLUSION: The combination of optical clearing and LSFM has new applications in
      dermatology and dermatological research by allowing 3D visualization and analysis
      of whole human skin biopsies.

PMID- 29377353
TI  - Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and
      enhances pain-related working memory deficits in neuropathic pain rats.
AB  - BACKGROUND: Dopamine (DA) is thought to be important to local hippocampal
      networks integrity during spatial working memory (sWM) processing. Chronic pain
      may contribute to deficient dopaminergic signalling, which may in turn affect
      cognition. However, the neural mechanisms that determine this impairment are
      poorly understood. Here, we evaluated whether the sWM impairment characteristic
      of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity.
      METHODS: To address this issue, we implanted multichannel arrays of electrodes in
      the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the
      neuronal activity during a classical delayed food-reinforced T-maze sWM task.
      Within-subject behavioural performance and patterns of dorsoventral neural
      activity were assessed before and after the onset of persistent neuropathic pain
      using the spared nerve injury (SNI) model. RESULTS: Our results show that the
      peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity
      and that disruption was maximized by the systemic administration of the D2r
      antagonist raclopride. These deficits are strictly correlated with a selective
      disruption of hippocampal theta-oscillations. Particularly, we found a
      significant decrease in intrahippocampal CA1 field connectivity level.
      CONCLUSIONS: Together, these results suggest that disruption of the dopaminergic
      balance in the intrahippocampal networks may be important for the development of
      cognitive deficits experienced during painful conditions. SIGNIFICANCE: This
      study provides new insights into the role of D2r in the manifestation of pain
      related sWM deficits. Our findings support that selective blockade of D2r
      produces a significant decrease in intrahippocampal connectivity mediated by
      theta-oscillations, and amplifies pain-related sWM deficits. These results
      suggest that further characterization of intrahippocampal dopaminergic modulation
      may be clinically relevant for the understanding of cognitive impairments that
      accompanies nociceptive stressful conditions.

PMID- 29377354
TI  - Redirecting adult mesenchymal stromal cells to the brain: a new approach for
      treating CNS autoimmunity and neuroinflammation?
AB  - Mesenchymal stromal cells or stem cells (MSCs) have been shown to participate in
      tissue repair and are immunomodulatory in neuropathological settings. Given this,
      their potential use in developing a new generation of personalized therapies for
      autoimmune and inflammatory diseases of the central nervous system (CNS) will be
      explored. To effectively exert these effector functions, MSCs must first gain
      entry into damaged neural tissues, a process that has been demonstrated to be a
      limiting factor in their therapeutic efficacy. In this review, we discuss
      approaches to maximize the therapeutic efficacy of MSCs by altering their
      intrinsic trafficking programs to effectively enter neuropathological sites. To
      this end, we explore the significant role of chemokine receptors and adhesion
      molecules in directing cellular traffic to the inflamed CNS and the capacity of
      MSCs to adopt these molecular mechanisms to gain entry to this site. We postulate
      that understanding and exploiting these migratory mechanisms may be key to the
      development of cell-based therapies tailored to respond to the migratory cues
      unique to the nature and stage of progression of individual CNS disorders.

PMID- 29377355
TI  - Gallbladder Agenesis in 17 Dogs: 2006-2016.
AB  - BACKGROUND: Gallbladder agenesis (GBA) is extremely rare in dogs.
      HYPOTHESIS/OBJECTIVES: To describe the history, clinical signs, diagnosis,
      treatment, and outcomes of dogs with GBA. ANIMALS: Seventeen client-owned dogs
      with GBA. METHODS: Medical records from 2006 through 2016 were retrospectively
      reviewed. Dogs were included when GBA was suspected on abdominal ultrasonography
      and confirmed by gross evaluation. Signalment, clinical signs,
      clinicopathological data, diagnostic imaging, histopathology, treatment, and
      outcome were recorded. RESULTS: Dogs were of 6 different breeds, and Chihuahuas
      (10 of 17) were most common. Median age at presentation was 1.9 (range, 0.7-7.4)
      years. Clinical signs included vomiting (5 of 17), anorexia (2 of 17), ascites (2
      of 17), diarrhea (1 of 17), lethargy (1 of 17), and seizures (1 of 17). All dogs
      had increased serum activity of at least 1 liver enzyme, most commonly alanine
      aminotransferase (15 of 17). Fifteen dogs underwent computed tomography (CT)
      cholangiography; common bile duct (CBD) dilatation was confirmed in 12, without
      evidence of bile duct obstruction. Gross evaluation confirmed malformation of the
      liver lobes in 14 of 17 dogs and acquired portosystemic collaterals in 5 of 17.
      Ductal plate malformation was confirmed histologically in 16 of 17 dogs. During
      follow-up (range, 4-3,379 days), 16 of 17 dogs remained alive. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Dogs with GBA exhibit clinicopathological signs of
      hepatobiliary injury and hepatic histopathological changes consistent with a
      ductal plate abnormality. Computed tomography cholangiography was superior to
      ultrasound examination in identifying accompanying nonobstructive CBD distention.
      Computed tomography cholangiography combined with laparoscopic liver biopsy is
      the preferable approach to characterize the full disease spectrum accompanying
      GBA in dogs.

PMID- 29377356
TI  - Efficacy of Oral Administration of Sodium Iodide to Prevent Bovine Respiratory
      Disease Complex.
AB  - BACKGROUND: The prevention of bovine respiratory disease complex (BRD) in beef
      cattle is important to maintaining health and productivity of calves in feeding
      operations. OBJECTIVE: Determine whether BRD bacterial and viral pathogens are
      susceptible to the lactoperoxidase/hydrogen peroxide/iodide (LPO/H2 O2 /I- )
      system in vitro and to determine whether the oral administration of sodium iodide
      (NaI) could achieve sufficient concentrations of iodine (I) in the respiratory
      secretions of weaned beef calves to inactivate these pathogens in vivo. ANIMALS:
      Sixteen weaned, apparently healthy, commercial beef calves from the University of
      Missouri, College of Veterinary Medicine teaching herd. METHODS: In vitro viral
      and bacterial assays were performed to determine susceptibility to the LPO/H2 O2
      /I- system at varying concentrations of NaI. Sixteen randomly selected, healthy
      crossbred beef weanlings were administered 70 mg/kg NaI, or water, orally in a
      blinded, placebo-controlled trial. Blood and nasal secretions were collected for
      72 hours and analyzed for I- concentration. RESULTS: Bovine herpesvirus-1,
      parainfluenza-3, Mannheimia haemolytica and Bibersteinia trehalosi were all
      inactivated or inhibited in vitro by the LPO/H2 O2 /I- reaction. Oral
      administration of NaI caused a marked increase in nasal fluid I concentration
      with a Cmax  = 181 (1,420 MUM I), T12 , a sufficient concentration to inactivate
      these pathogens in vitro. CONCLUSIONS AND CLINICAL IMPORTANCE: In vitro, the
      LPO/H2 O2 /I- system inactivates and inhibits common pathogens associated with
      BRD. The administration of oral NaI significantly increases the I concentration
      of nasal fluid indicating that this system might be useful in preventing bovine
      respiratory infections.

PMID- 29377358
TI  - Erratum.

PMID- 29377357
TI  - Rapid Diagnosis of Babesia gibsoni by Point-of-Need Testing by Insulated
      Isothermal PCR in Dogs at High Risk of Infection.
AB  - BACKGROUND: Dogs seized by law enforcement agencies during dogfighting
      investigations are at increased risk of Babesia gibsoni infection. A rapid and
      cost-effective diagnostic test would increase the feasibility of mass screening
      of dogs for infection and monitoring treatment efficacy in B. gibsoni-infected
      dogs. OBJECTIVE: To determine the performance of a point-of-need insulated
      isothermal PCR (iiPCR) test for diagnosis of B. gibsoni in dogs rescued in
      dogfighting investigations. ANIMALS: Two hundred and thirty-three dogs seized in
      dogfighting investigations. METHODS: Cross-sectional study. Whole blood samples
      were tested for B. gibsoni and Babesia spp. by iiPCR. Results were compared to a
      reference standard comprised of concordant results from real-time PCR in a
      commercial diagnostic laboratory and antibody titers. RESULTS: The iiPCR system
      was quick to learn, portable, and had a short processing time of <2 hours.
      Sensitivity and specificity of the iiPCR assay for B. gibsoni were 90% (95%
      confidence interval [CI] 81-95%) and 99% (CI, 95-100%), respectively. Sensitivity
      and specificity of the iiPCR assay for Babesia spp. were 87% (CI, 78-93%) and 98%
      (CI, 0.94-99%), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The iiPCR
      system produced few false-positive results, indicating that positive results are
      likely to represent true infections when used in high-risk animals. The iiPCR
      system can fail to identify 10-15% of truly infected dogs. However, the
      portability, speed, and economy of the iiPCR system compared to testing through a
      reference laboratory can allow rescue groups to screen and identify infection in
      more dogs.

PMID- 29377359
TI  - Decreased Clinical Severity of Strangles in Weanlings Associated with Restricted
      Seroconversion to Optimized Streptococcus equi ssp equi Assays.
AB  - BACKGROUND: Streptococcus equi ssp. equi causes characteristic clinical signs
      that are most severe in young horses, including fever, purulent nasal discharge,
      and lymph node abscessation in the head region. HYPOTHESIS/OBJECTIVES: Clinical,
      serologic, and microbiologic factors related to unexpectedly mild disease
      severity in a natural outbreak of strangles in immunologically naive weanlings
      were investigated. ANIMALS: One-hundred and twelve warmblood weanlings. METHODS:
      Prospective longitudinal observational study of a natural outbreak of strangles.
      The entire cohort was examined at the peak of the outbreak by deep nasal swabs
      for culture and quantitative PCR (qPCR) for the presence of S. equi and
      clinically and serologically in a sequential manner by an optimized ELISA from
      the index case throughout the outbreak until resolution. Descriptive statistics
      were calculated and comparisons made using a nondirectional Wilcoxon signed-rank
      test. RESULTS: Outbreak morbidity was 53%, with 9 of 14 horses culture positive
      and 26 of 53 horses qPCR positive for S. equi lacking clinical signs
      characteristic of strangles. By resolution, 91 of 112 had seroconverted to
      Antigen A by ELISA but seroconversion to antigen C (part of the SeM protein) was
      minimal. Sequencing of the isolates detected no alterations in the SeM protein,
      but identified a 61 bp deletion in the gene SEQ_0402. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Absence of clinical signs alone in naive horses may be an
      insufficient criterion to release horses from strangles quarantine measures.
      Restricted seroconversion to antigen C may have been associated with decreased
      clinical severity. The role of a minor gene deletion in SEQ_0402 in the virulence
      of S. equi warrants further investigation.

PMID- 29377360
TI  - Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for
      Masked Chronic Kidney Disease in Cats With Hyperthyroidism.
AB  - BACKGROUND: Hyperthyroidism can complicate (mask) the diagnosis of chronic kidney
      disease (CKD) because it increases glomerular filtration rate and decreases body
      muscle mass, both of which can lower serum creatinine concentrations. Currently,
      there is no clinical test that can reliably predict which hyperthyroid cats have
      concurrent azotemic CKD that will become apparent after treatment of the
      hyperthyroidism. OBJECTIVES: To investigate serum symmetric dimethylarginine
      (SDMA) concentration as a potential marker of masked azotemia in untreated
      hyperthyroid cats. ANIMALS: Two hundred and sixty-two hyperthyroid cats and 206
      aged-matched, clinically normal cats. METHODS: Prospective study. We measured
      creatinine, urea nitrogen, SDMA, T4 , and TSH concentrations before and 1, 3, and
      6 months after treatment with radioiodine (131 I) and classified 131 I-treated
      cats as azotemic or nonazotemic based on persistent, post-treatment creatinine
      concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and
      diagnostic accuracy was determined by receiver operating characteristic analysis
      and logistic regression. RESULTS: No hyperthyroid cats were azotemic before
      treatment, but 42 (16%) became azotemic when rechecked at 4-8 months (median, 6
      months) after 131 I treatment; of these, 14 had high SDMA concentrations before
      treatment. As a diagnostic test for pre-azotemic (masked) CKD in untreated
      hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Finding a high serum SDMA concentration in a
      hyperthyroid cat can help predict development of azotemia after treatment. The
      test has high diagnostic test specificity (few false-positive results) but
      relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).

PMID- 29377362
TI  - Unrecorded alcohol use: a global modelling study based on nominal group
      assessments and survey data.
AB  - BACKGROUND AND AIMS: Alcohol use is among the most important risk factors for
      burden of disease globally. An estimated quarter of the total alcohol consumed
      globally is unrecorded. However, due partly to the challenges associated with its
      assessment, evidence concerning the magnitude of unrecorded alcohol use is
      sparse. This study estimated country-specific proportions of unrecorded alcohol
      used in 2015. DESIGN: A statistical model was developed for data prediction using
      data on the country-specific proportion of unrecorded alcohol use from nominal
      group expert assessments and secondary, nationally representative survey data and
      country-level covariates. SETTING: Estimates were calculated for the country
      level, for four income groups and globally. PARTICIPANTS: A total of 129
      participants from 49 countries were included in the nominal group expert
      assessments. The survey data comprised 66 538 participants from 16 countries.
      MEASUREMENTS: Experts completed a standardized questionnaire assessing the
      country-specific proportion of unrecorded alcohol. In the national surveys, the
      number of standard drinks of total and unrecorded alcohol use was assessed for
      the past 7 days. FINDINGS: Based on predictions for 167 countries, a population
      weighted average of 27.9% [95% confidence interval (CI) = 10.4-44.9%] of the
      total alcohol consumed in 2015 was unrecorded. The proportion of unrecorded
      alcohol was lower in high (9.4%, 95% CI = 2.4-16.4%) and upper middle-income
      countries (18.3%, 95% CI = 9.0-27.6%) and higher in low (43.1%, 95% CI = 26.5
      59.7%) and lower middle-income countries (54.4%, 95% CI = 38.1-70.8%). This
      corresponded to 0.9 (high-income), 1.2 (upper middle-income), 3.2 (lower middle
      income) and 1.8 (low-income) litres of unrecorded alcohol per capita.
      CONCLUSIONS: A new method for modelling the country-level proportion of
      unrecorded alcohol use globally showed strong variation among geographical
      regions and income groups. Lower-income countries were associated with a higher
      proportion of unrecorded alcohol than higher-income countries.

PMID- 29377361
TI  - Echocardiographic Evaluation of the Right Atrial Area Index in Dogs with
      Pulmonary Hypertension.
AB  - BACKGROUND: Right atrial area (RAA) is a prognostic factor in human patients with
      pulmonary arterial hypertension (PAH). Reference intervals for RAA have been
      described in healthy dogs. OBJECTIVES: To evaluate RAA indexed to the body
      surface area in dogs with PAH as an indicator of right atrial size, PAH severity
      and right-sided congestive heart failure (R-CHF). ANIMALS: A total of 119 client
      owned dogs, 48 dogs with PAH and 71 control dogs. METHODS: Prospective
      observational study. Pulmonary arterial hypertension was classified according to
      the tricuspid regurgitation pressure gradient (TRPG) as mild (36-50 mmHg),
      moderate (51-75 mmHg), or severe (>75 mmHg). The RAA index was calculated as the
      RAA divided by body surface area. RESULTS: The RAA index was higher in dogs with
      moderate PAH (13.3 cm2 /m2 ; range, 3.4-24.7 cm2 /m2 ) and severe PAH (12.1 cm2
      /m2 ; range, 5.4-21.8 cm2 /m2 ) than in those with mild PAH (6.7 cm2 /m2 ; range,
      4.8-10.7 cm2 /m2 ) or in controls (7.3 cm2 /m2 ; range, 4.2-10.2 cm2 /m2 ; P <
      0.001). The RAA index was higher (P < 0.0001) in dogs with R-CHF (17.5 cm2 /m2 ;
      range, 12.7-24.7 cm2 /m2 ) compared to those without R-CHF (7.6 cm2 /m2 ; range,
      4.4-19.4 cm2 /m2 ). The most accurate cutoff value of the RAA index to identify R
      CHF was >12.3 cm2 /m2 (sensitivity, 100%; specificity, 89.5%). In dogs with PAH,
      severity of tricuspid regurgitation (TR) was the only independent predictor of
      RAA index based on multivariate analysis (P < 0.02). CONCLUSIONS AND CLINICAL
      IMPORTANCE: The RAA index can be used to evaluate right atrial size in dogs and
      may be more effective than TRPG in predicting R-CHF in dogs with PAH. The
      severity of TR is the main determinant of the RAA index in dogs with PAH.

PMID- 29377363
TI  - Antimicrobial properties of melanocortins: comment to the manuscript "Anti
      Candida activity of alpha-melanocyte-stimulating hormone (alpha-MSH) peptides" by
      Isabella Rauch et al.
AB  - In their report, Rauch et al. did not find candidacidal activity of alpha
      melanocyte-stimulating hormone (alpha-MSH) in Sabouraud dextrose broth. The lack
      of killing activity by the natural alpha-MSH in broth medium may occur because of
      accelerated Candida replication or peptide degradation by fungal enzymes. It
      should be considered that in physiological conditions, there is sustained peptide
      release by host cells in an autocrine/paracrine manner. However, when the
      procedure described in the paper published in the Journal Leukocyte Biology was
      used, the investigation by Rauch et al. found that concentrations of alpha-MSH in
      the high micromolar range have candidacidal activity.

PMID- 29377364
TI  - Multicenter, randomized, controlled trial of S-1 monotherapy versus S-1 and
      interferon-alpha combination therapy for hepatocellular carcinoma with
      extrahepatic metastases.
AB  - AIM: No effective therapies for extrahepatic metastases from hepatocellular
      carcinoma (HCC) have yet been identified. Previous studies suggested a
      potentially promising antitumor effect of combination therapy of S-1, a novel
      oral dihydropyrimidine dehydrogenase inhibitor, and interferon (IFN)-alpha. The
      present study aimed to investigate the clinical efficacy of single agent S-1 and
      S-1/IFN-alpha for HCC patients with extrahepatic metastases in a randomized, open
      label, multicenter trial. METHODS: A total of 103 patients with HCC with
      extrahepatic metastases were randomly assigned to the S-1/IFN-alpha group,
      receiving the combination of S-1 and IFN-alpha, or the S-1 group, receiving the
      single agent of S-1. Clinical efficacy and adverse events were compared between
      the two groups. RESULTS: A total of 49 patients in the S-1/IFN-alpha group and 51
      patients in the S-1 group were included in the efficacy analysis. The response
      rate was 22.4% (11/49) in the S-1/IFN-alpha group and 13.7% (7/51) in the S-1
      group; there was no significant difference. Overall and progression-free survival
      in the two groups were also not significantly different (1-year overall survival
      50.8% vs. 72.4%, median progression-free survival 127 days vs. 157 days). The
      incidence of grade >=3 adverse events in the S-1/IFN-alpha group was 62.7%
      (32/51), which tended to be higher than in the S-1 group (43.1% [22/51]).
      CONCLUSIONS: Oncological outcomes in both treatment groups were favorable
      compared with previous reports, though there was no significant beneficial effect
      of adding IFN-alpha to S-1 for the treatment of HCC patients with extrahepatic
      metastases.

PMID- 29377365
TI  - Neonatal exposure to oestradiol increases dopaminergic transmission in nucleus
      accumbens and morphine-induced conditioned place preference in adult female rats.
AB  - Steroid sex hormones produce physiological effects in reproductive tissues and
      also in nonreproductive tissues, such as the brain, particularly in cortical,
      limbic and midbrain areas. Dopamine (DA) neurones involved in processes such as
      prolactin secretion (tuberoinfundibular system), motor circuit regulation
      (nigrostriatal system) and driving of motivated behaviour (mesocorticolimbic
      system) are specially regulated by sex hormones. Indeed, sex hormones promote
      neurochemical and behavioural effects induced by drugs of abuse by tuning
      midbrain DA neurones in adult animals. However, the long-term effects induced by
      neonatal exposure to sex hormones on dopaminergic neurotransmission have not been
      fully studied. The present study aimed to determine whether a single neonatal
      exposure with oestradiol valerate (EV) results in a programming of dopaminergic
      neurotransmission in the nucleus accumbens (NAcc) of adult female rats. To answer
      this question, electrophysiological, neurochemical, cellular, molecular and
      behavioural techniques were used. The data show that frequency but not amplitude
      of the spontaneous excitatory postsynaptic current is significantly increased in
      NAcc medium spiny neurones of EV-treated rats. In addition, DA content and
      release are both increased in the NAcc of EV-treated rats, caused by an increased
      synthesis of this neurotransmitter. These results are functionally associated
      with a higher percentage of EV-treated rats conditioned to morphine, a drug of
      abuse, compared to controls. In conclusion, neonatal programming with oestradiol
      increases NAcc dopaminergic neurotransmission in adulthood, which may be
      associated with increased reinforcing effects of drugs of abuse.

PMID- 29377366
TI  - Matrine reduces susceptibility to postinfarct atrial fibrillation in rats due to
      antifibrotic properties.
AB  - This study aimed to investigate whether matrine could prevent atrial fibrillation
      (AF) after myocardial infarction by reducing left atrial fibrosis, and to
      determine the underlying mechanisms in isolated cardiac fibroblasts (CFs). Five
      weeks after MI, matrine-treated rats had lower rates of AF inducibility and
      shorter AF duration than MI rats. Matrine improved the left atrial conduction
      velocity and homogeneity. Matrine decreased the fibrosis positive areas and the
      protein levels of type I collagen and type III collagen in the left atrium.
      Matrine inhibited CFs differentiation to myofibroblasts and the expression of
      transforming growth factor-beta 1 and matrix metalloproteinase 9. In vitro,
      matrine inhibited the CFs proliferation, migration, differentiation, and
      secretion ability. These in vitro and in vivo data demonstrated that matrine has
      the potential to reduce susceptibility to AF after MI due, at least in part, to
      reduced atrial fibrosis via inhibiting CFs proliferation, migration,
      differentiation, and secretion ability.

PMID- 29377367
TI  - Cyclolinear Oligo- and Poly(iminoborane)s: The Missing Link in Inorganic Main
      Group Macromolecular Chemistry.
AB  - The reaction of n-C8 H17 B[N(Me)SiMe3 ]2 (1) with n-C8 H17 BCl2 (2 a) yielded,
      instead of a linear poly(iminoborane), the aminoborane n-C8 H17 B(Cl)N(Me)SiMe3
      (4) and after cyclotrimerization the borazine cyclo-(n-C8 H17 BNMe)3 (6). Side
      reactions that result in borazine formation were effectively suppressed if 1,3
      bis(trimethylsilyl)-1,3,2-diazaborolidines 7 were employed as co-monomers in
      combination with dichloro- or dibromoboranes 2 or 8, respectively. Silicon/boron
      exchange polycondensation led to oligo(iminoborane)s 11 a,b,ac,d. Alternative
      synthetic routes to such species involve Sn/B exchange of 1,3
      bis(trimethylstannyl)-2-n-octyl-1,3,2-diazaborolidine (16) and n-C8 H17 BBr2 (8
      a), and the initiated polycondensation of the dormant monomer 14 in the presence
      of a Bronsted acid (HCl, HOTf, or HNTf2 ; Tf=trifluoromethylsulfonyl). Although
      an attempt to obtain an oligo-/poly(iminoborane) with phenyl side groups yielded
      only insoluble material, the incorporation of aryl groups was proven for a
      derivative with both phenyl and n-octyl boron substituents (11 ac), as well as
      for a derivative with 4-n-butylphenyl side groups (11 d). The highest-molecular
      weight sample obtained was 11 ac. Featuring about 18 catenated BN units, on
      average, this is the closest approach to a poly(iminoborane) known.

PMID- 29377368
TI  - A systematic review of fluconazole resistance in clinical isolates of
      Cryptococcus species.
AB  - Fluconazole is the most commonly used antifungal agent for both the treatment of
      cryptococcal meningitis, and for prophylaxis against the disease. However, its
      prolonged use has the potential to exert selection pressure in favour of
      fluconazole-resistant strains. We evaluated the prevalence of fluconazole
      resistance in Cryptococcus spp. clinical isolates in 29 studies from 1988 to May
      2017 included in EMBASE and MEDLINE databases. A total of 4995 Cryptococcus
      isolates from 3210 patients constituted this study; 248 (5.0%) of the isolates
      from relapsed episodes of cryptococcosis were included in this analysis. Eleven
      (38%) of the studies used minimum inhibitory concentrations (MICs) breakpoints of
      >=64 MUg/mL to define fluconazole resistance, 6 (21%) used >=32 MUg/mL, 11 (38%)
      used >=16 MUg/mL and 1 (3%) used <=20 MUg/mL. Overall, mean prevalence of
      fluconazole resistance was 12.1% (95% confidence interval [CI]: 6.7-17.6) for all
      isolates (n = 4995). Mean fluconazole resistance was 10.6% (95% CI: 5.5-15.6) for
      the incident isolates (n = 4747) and 24.1% (95% CI: -3.1-51.2) for the relapse
      isolates (n = 248). Of the 4995 isolates, 936 (18.7%) had MICs above the
      ecological cut-off value. Fluconazole resistance appears to be an issue in
      Cryptococcus isolates from patients with relapses. It remains unclear whether
      relapses occur due to resistance or other factors. There is an urgent need to
      establish antifungal breakpoints for Cryptococcus spp.

PMID- 29377369
TI  - Two Diterpene Synthases for Spiroalbatene and Cembrene A from Allokutzneria
      albata.
AB  - Two bacterial diterpene synthases from the actinomycete Allokutzneria albata were
      investigated, resulting in the identification of the structurally unprecedented
      compound spiroalbatene from the first and cembrene A from the second enzyme. Both
      enzymes were thoroughly investigated in terms of their mechanisms by isotope
      labeling experiments, site-directed mutagenesis, and variation of the metal
      cofactors and pH value. For spiroalbatene synthase, the pH- and Mn2+ -dependent
      formation of the side product thunbergol was observed, which is biosynthetically
      linked to spiroalbatene.

PMID- 29377370
TI  - Mechanism of Ultrafast Intersystem Crossing in 2-Nitronaphthalene.
AB  - Nitronaphthalene derivatives efficiently populate their electronically excited
      triplet states upon photoexcitation through ultrafast intersystem crossing (ISC).
      Despite having been studied extensively by time-resolved spectroscopy, the
      reasons behind their ultrafast ISC remain unknown. Herein, we present the first
      ab initio nonadiabatic molecular dynamics study of a nitronaphthalene derivative,
      2-nitronaphthalene, including singlet and triplet states. We find that there are
      two distinct ISC reaction pathways involving different electronic states at
      distinct nuclear configurations. The high ISC efficiency is explained by the very
      small electronic and nuclear alterations that the chromophore needs to undergo
      during the singlet-triplet transition in the dominating ISC pathway after initial
      dynamics in the singlet manifold. The insights gained in this work are expected
      to shed new light on the photochemistry of other nitro polycyclic aromatic
      hydrocarbons that exhibit ultrafast intersystem crossing.

PMID- 29377371
TI  - Progeria: case report and new drugs perspectives.

PMID- 29377372
TI  - Restorative Treatment in Patients with Amelogenesis Imperfecta: A Review.
AB  - PURPOSE: To summarize the contemporary scientific evidence available regarding
      restorative dental treatment in patients with Amelogenesis imperfecta (AI).
      METHODS: An electronic literature search was conducted using the search term
      "Amelogenesis imperfecta" and the PubMed/MEDLINE database as well as Google
      Scholar. Prospective and retrospective clinical studies that investigated the
      outcome of direct and/or indirect dental restorative treatment in patients with
      AI, were published in English, and had an observation time of at least 1 year
      were included in this review. The articles identified were screened and analyzed
      by two reviewers according to inclusion and exclusion criteria in three review
      rounds. RESULTS: Six prospective or retrospective clinical studies analyzing
      longevity and complications associated with dental restorative treatment in
      patients with AI met the inclusion criteria. Extracted data suggest that in
      patients with AI, indirect restorations feature superior predictability and
      longevity than direct restorations. CONCLUSIONS: As endodontic complications were
      infrequently observed and periodontal parameters regularly improve with the
      insertion of indirect restorations, dental treatment in patients with AI should
      focus on indirect restorations as soon as possible. While adhesive bonding
      techniques to enamel surfaces in patients with AI feature merely limited
      predictability and longevity and as the available data is scarce, further
      laboratory and clinical studies should be performed to investigate the
      performance of minimally invasive indirect restorations bonded to enamel in
      patients with AI. RECOMMENDATION: Scientific evidence indicates that indirect
      restorations should be preferred over direct restorations in patients with AI.

PMID- 29377373
TI  - In response to 'benefits and risks of intensive blood-pressure lowering in
      advanced chronic kidney disease'.

PMID- 29377374
TI  - Identification of small molecular inhibitors for efflux protein Rv2688c of
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb) is the pathogen, which causes tuberculosis. The
      development of multidrug-resistant and extensively drug-resistant strains in Mtb
      is due to an efflux mechanism of antibiotics in the bacteria. The efflux pump
      proteins in the bacteria are implicated in the active efflux of antibiotics. The
      efflux pump protein, "fluoroquinolones export ATP-binding protein Rv2688c"
      (FEAB), is considered as a potential therapeutic target to prevent tuberculosis.
      In the present work, in silico protocols are applied to identify inhibitors for
      the FEAB protein to arrest the efflux mechanism. Comparative modeling techniques
      are used to build the protein structure. The generated structure consists of 9
      helices, 13 beta strands, and 3 beta sheets. The active site is predicted using
      active site prediction server tools. The virtual screening protocols are carried
      out to generate small ligand inhibitor structures. The identified ligand
      molecules show selective binding with Ser97, Glu99, Lys149, Asp171, Glu172, and
      Ser175 amino acid residues of the protein. The ligand molecules are subjected to
      in silico prediction of pharmaco kinetic properties, and the predicted IC50
      (HERG) of all the molecules are less than -5.0, which is indicative of the
      identified ligand molecules is being potentially good FEAB inhibitors.

PMID- 29377375
TI  - Ethanol stress in Oenococcus oeni: transcriptional response and complex
      physiological mechanisms.
AB  - Oenococcus oeni is the dominant species able to cope with a hostile environment
      of wines, comprising cumulative effects of low pH, high ethanol and SO2 content,
      nonoptimal growth temperatures and growth inhibitory compounds. Ethanol tolerance
      is a crucial feature for the activity of O. oeni cells in wine because ethanol
      acts as a disordering agent of its cell membrane and negatively affects metabolic
      activity; it damages the membrane integrity, decreases cell viability and, as
      other stress conditions, delays the start of malolactic fermentation with a
      consequent alteration of wine quality. The cell wall, cytoplasmic membrane and
      metabolic pathways are the main sites involved in physiological changes aimed to
      ensure an adequate adaptive response to ethanol stress and to face the oxidative
      damage caused by increasing production of reactive oxygen species. Improving our
      understanding of the cellular impact of ethanol toxicity and how the cell
      responds to ethanol stress can facilitate the development of strategies to
      enhance microbial ethanol tolerance; this allows to perform a multidisciplinary
      endeavour requiring not only an ecological study of the spontaneous process but
      also the characterization of useful technological and physiological features of
      the predominant strains in order to select those with the highest potential for
      industrial applications.

PMID- 29377377
TI  - The haemodynamic response to incremental increases in negative intrathoracic
      pressure in healthy humans.
AB  - NEW FINDINGS: What is the central question of this study? The haemodynamic
      response to incremental increases in negative intrathoracic pressure (nITP)
      during spontaneous breathing and the mechanisms of cardiac impairment at these
      levels of nITP remain unclear. What is the main finding and its importance? nITP
      of -20 cmH2 O or greater reduces stroke volume in healthy, spontaneously
      breathing supine humans due to direct ventricular interaction and increased left
      ventricular afterload. ABSTRACT: Negative intrathoracic pressure (nITP) generally
      augments venous return and left ventricular (LV) stroke volume (LVSV), though
      large increases in nITP, commonly seen in respiratory disease, attenuate LVSV.
      Despite this consistent finding, the degree of nITP required to reduce LVSV and
      the contributions of series and direct ventricular interaction (DVI) in mediating
      this response remain unclear. We hypothesized that nITP <=-15 cmH2 O would
      augment LVSV, while nITP >=-20 cmH2 O would reduce LVSV via DVI and increased
      afterload. Twenty-three healthy subjects were randomly given inspiratory loads
      during spontaneous breathing to generate -5, -10, -15, -20 and -25 cmH2 O. LV
      volumes, LV geometry, inferior vena cava collapsibility (cIVC) and LV end
      systolic meridional wall-stress (LVESMWS) were assessed in the supine position
      using tri-plane echocardiography. LVSV remained unchanged up to -15 cmH2 O, but
      was significantly reduced at nITP >=-20 cmH2 O (-12 +/- 8% and -15 +/- 11% at -20
      and -25 cmH2 O, respectively, P < 0.05) due to significant reductions in LV end
      diastolic volume (LVEDV), while LV end-systolic volume was unchanged. cIVC on
      inspiration was significantly increased at all levels of nITP, while LVESMWS only
      increased at -25 cmH2 O (P < 0.05). DVI, as indicated by a significant increase
      in the radius of septal curvature, occurred at nITP >=-10 cmH2 O. In supine
      healthy humans, nITP <=-15 cmH2 O does not significantly affect LV function,
      despite increased DVI. In contrast, nITP >=-20 cmH2 O causes significant
      reductions in LVSV and LVEDV, which appear to be mediated by DVI and increased
      afterload at -25 cmH2 O. The impact of cIVC during nITP remains unclear.

PMID- 29377376
TI  - Cost-effectiveness of intravenous acetaminophen and ketorolac in adolescents
      undergoing idiopathic scoliosis surgery.
AB  - BACKGROUND: Enhanced recovery after surgery protocols increasingly use multimodal
      analgesia after major surgeries with intravenous acetaminophen and ketorolac,
      despite no documented cost-effectiveness of these strategies. AIMS: The goal of
      this prospective cohort study was to model cost-effectiveness of adding
      acetaminophen or acetaminophen + ketorolac to opioids for postoperative outcomes
      in children having scoliosis surgery. METHODS: Of 106 postsurgical children, 36
      received only opioids, 26 received intravenous acetaminophen, and 44 received
      acetaminophen + ketorolac as analgesia adjuncts. Costs were calculated in 2015 US
      $. Decision analytic model was constructed with Decision Maker(r) software. Base
      case and sensitivity analyses were performed with effectiveness defined as
      avoidance of opioid adverse effects. RESULTS: The groups were comparable
      demographically. Compared with opioids-only strategy, subjects in the intravenous
      acetaminophen + ketorolac strategy consumed less opioids (P = .002; difference in
      mean morphine consumption on postoperative days 1 and 2 was -0.44 mg/kg (95% CI 
      0.72 to -0.16); tolerated meals earlier (P < .001; RR 0.250 (0.112-0.556)) and
      had less constipation (P < .001; RR 0.226 (0.094-0.546)). Base-case analysis
      showed that of the 3 strategies, use of opioids alone is both most costly and
      least effective, opioids + intravenous acetaminophen is intermediate in both cost
      and effectiveness; and opioids + intravenous acetaminophen and ketorolac is the
      least expensive and most effective strategy. The addition of intravenous
      acetaminophen with or without ketorolac to an opioid-only strategy saves $510
      $947 per patient undergoing spine surgery and decreases opioid side effects.
      CONCLUSION: Intravenous acetaminophen with or without ketorolac reduced opioid
      consumption, opioid-related adverse effects, length of stay, and thereby cost of
      care following idiopathic scoliosis in adolescents compared with opioids-alone
      postoperative analgesia strategy.

PMID- 29377379
TI  - SPHK1-S1PR1-RANKL Axis Regulates the Interactions Between Macrophages and BMSCs
      in Inflammatory Bone Loss.
AB  - Accumulating evidence indicates that the immune and skeletal systems interact
      with each other through various regulators during the osteoclastogenic process.
      Among these regulators, the bioactive lipid sphingosine-1-phosphate (S1P), which
      is synthesized by sphingosine kinase 1/2 (SPHK1/2), has recently been recognized
      to play a role in immunity and bone remodeling through its receptor sphingosine-1
      phosphate receptor 1 (S1PR1). However, little is known regarding the potential
      role of S1PR1 signaling in inflammatory bone loss. We observed that SPHK1 and
      S1PR1 were upregulated in human apical periodontitis, accompanied by macrophage
      infiltration and enhanced expression of receptor activator of NF-kappaB ligand
      (RANKL, an indispensable factor in osteoclastogenesis and bone resorption) and
      increased numbers of S1PR1-RANKL double-positive cells in lesion tissues. Using
      an in vitro co-culture model of macrophages and bone marrow stromal cells
      (BMSCs), it was revealed that in the presence of lipopolysaccharide (LPS)
      stimulation, macrophages could significantly induce SPHK1 activity, which
      resulted in activated S1PR1 in BMSCs. The activated S1P-S1PR1 signaling was
      responsible for the increased RANKL production in BMSCs, as S1PR1-blockage
      abolished this effect. Applying a potent S1P-S1PR1 signaling modulator,
      Fingolimod (FTY720), in a Wistar rat apical periodontitis model effectively
      prevented bone lesions in vivo via downregulation of RANKL production,
      osteoclastogenesis, and bone resorption. Our data unveiled the regulatory role of
      SPHK1-S1PR1-RANKL axis in inflammatory bone lesions and proposed a potential
      therapeutic intervention by targeting this cell-signaling pathway to prevent bone
      loss. (c) 2018 American Society for Bone and Mineral Research.

PMID- 29377380
TI  - Obstetric intra-operative cell salvage and maternal fetal red cell contamination.
AB  - BACKGROUND: The significance of fetal red blood cell (RBC) contamination in
      obstetric intra-operative cell salvage is not fully known. It is unclear if we re
      infuse a larger volume of fetal RBCs into the maternal circulation than the
      amount that occurs secondary to transplacental haemorrhages is unclear. We also
      do not know if there is a critical volume required to cause alloimmunisation or
      if larger volumes increase the risk. OBJECTIVES: The aim of this study is to
      provide data on the level of fetal RBC contamination in the maternal circulation
      prior to delivery and immediately post-partum and to compare these levels to
      those found in processed cell-salvaged blood. METHODS: In the first part of this
      study, we quantified the levels of fetal RBCs circulating in women immediately
      prior to delivery. This was then repeated with a separate group measuring the
      levels of fetal RBCs pre- and post-delivery. RESULTS: We found that 37% of women
      had fetal cells detected in their circulation, median 0.00 mL (IQR 0-0.24;
      average 0.3 mL, maximum 4.56 mL). Fetal RBCs were present pre-delivery (maximum
      0.66 mL) in 16% of women, increasing to 53% post-delivery (median 0.66 mL; IQR
      0.22-2.20, maximum 21.20 mL). CONCLUSIONS: We have shown that fetal RBCs are
      present in the maternal circulation throughout pregnancy and that the volumes are
      comparable to that obtained from intra-operative salvage, with contamination
      amounts of up to 19 mL. At the Royal Cornwall Hospital, our experience and
      evidence supports offering intra-operative salvage to all women, and we have not
      noted an increase in antibody formation, compared to allogeneic transfusion.

PMID- 29377378
TI  - Evaluation of a Multimodal, Direct-to-Patient Educational Intervention Targeting
      Barriers to Osteoporosis Care: A Randomized Clinical Trial.
AB  - Osteoporosis treatment rates are declining, even among those with past fractures.
      Novel, low-cost approaches are needed to improve osteoporosis care. We conducted
      a parallel group, controlled, randomized clinical trial evaluating a behavioral
      intervention for improving osteoporosis medication use. A total of 2684 women
      with self-reported fracture history after age 45 years not using osteoporosis
      therapy from US Global Longitudinal Study of Osteoporosis in Women (GLOW) sites
      were randomized 1:1 to receive a multimodal, tailored, direct-to-patient, video
      intervention versus usual care. The primary study outcome was self-report of
      osteoporosis medication use at 6 months. Other outcomes included calcium and
      vitamin D supplementation, bone mineral density (BMD) testing, readiness for
      behavioral change, and barriers to treatment. In intent-to-treat analyses, there
      were no significant differences between groups (intervention versus control) in
      osteoporosis medication use (11.7% versus 11.4%, p = 0.8), calcium
      supplementation (31.8% versus 32.6%, p = 0.7), vitamin D intake (41.3% versus
      41.9%, p = 0.8), or BMD testing (61.8% versus 57.1%, p = 0.2). In the
      intervention group, fewer women were in the precontemplative stage of behavior
      change, more women reported seeing their primary care provider, had concerns
      regarding osteonecrosis of the jaw, and difficulty in taking/remembering to take
      osteoporosis medications. We found differences in BMD testing among the subgroup
      of women with no prior osteoporosis treatment, those who provided contact
      information, and those with no past BMD testing. In per protocol analyses, women
      with appreciable exposure to the online intervention (n = 257) were more likely
      to start nonbisphosphonates (odds ratio [OR] = 2.70; 95% confidence interval [CI]
      1.26-5.79) compared with the usual care group. Although our intervention did not
      increase the use of osteoporosis therapy at 6 months, it increased
      nonbisphosphonate medication use and BMD testing in select subgroups, shifted
      participants' readiness for behavior change, and altered perceptions of barriers
      to osteoporosis treatment. Achieving changes in osteoporosis care using patient
      activation approaches alone is challenging. (c) 2018 American Society for Bone
      and Mineral Research.

PMID- 29377381
TI  - Medical cannabis: A forward vision for the clinician.
AB  - : Medical cannabis has entered mainstream medicine and is here to stay. Propelled
      by public advocacy, the media and mostly anecdote rather than sound scientific
      study, patients worldwide are exploring marijuana use for a vast array of medical
      conditions including management of chronic pain. Contrary to the usual path of
      drug approval, medical cannabis has bypassed traditional evidence-based study and
      has been legalized as a therapeutic product by legislative bodies in various
      countries. While there is a wealth of basic science and preclinical studies
      demonstrating effects of cannabinoids in neurobiological systems, especially
      those pertaining to pain and inflammation, clinical study remains limited.
      Cannabinoids may hold promise for relief of symptoms in a vast array of
      conditions, but with many questions as yet unanswered. Rigorous study is needed
      to examine the true evidence for benefits and risks for various conditions and in
      various patient populations, the specific molecular effects, ideal methods of
      administration, and interaction with other medications and substances. In the
      context of prevalent use, there is an urgency to gather pertinent clinical
      information about the therapeutic effects as well as risks. Even with
      considerable uncertainties, the health care community must adhere to the guiding
      principle of clinical care 'primum non nocere' and continue to provide empathetic
      patient care while exercising prudence and caution. The health care community
      must strongly advocate for sound scientific evidence regarding cannabis as a
      therapy. SIGNIFICANCE: Legalization of medical cannabis has bypassed usual drug
      regulatory procedures in jurisdictions worldwide. Pending sound evidence for
      effect in many conditions, physicians must continue to provide competent
      empathetic care with attention to harm reduction. A vision to navigate the
      current challenges of medical cannabis is outlined.

PMID- 29377382
TI  - Re: Vaginal seeding or vaginal microbial transfer from the mother to the
      caesarean-born neonate: a commentary regarding clinical management.

PMID- 29377383
TI  - Continuous Heterogeneous Photocatalysis in Serial Micro-Batch Reactors.
AB  - Solid reagents, leaching catalysts, and heterogeneous photocatalysts are commonly
      employed in batch processes but are ill-suited for continuous-flow chemistry.
      Heterogeneous catalysts for thermal reactions are typically used in packed-bed
      reactors, which cannot be penetrated by light and thus are not suitable for
      photocatalytic reactions involving solids. We demonstrate that serial micro-batch
      reactors (SMBRs) allow for the continuous utilization of solid materials together
      with liquids and gases in flow. This technology was utilized to develop selective
      and efficient fluorination reactions using a modified graphitic carbon nitride
      heterogeneous catalyst instead of costly homogeneous metal polypyridyl complexes.
      The merger of this inexpensive, recyclable catalyst and the SMBR approach enables
      sustainable and scalable photocatalysis.

PMID- 29377384
TI  - Paris saponin VII induces cell cycle arrest and apoptosis by regulating Akt/MAPK
      pathway and inhibition of P-glycoprotein in K562/ADR cells.
AB  - Paris saponinVII (PSVII) is a steroidal saponin isolated from the roots and
      rhizomes of Trillium tschonoskii Maxim. We found that PSVII could inhibit the
      growth of adriamycin-resistant human leukemia cells (K562/ADR) in a dose
      dependent manner. Furthermore, the molecular mechanism underlying the
      cytotoxicity and downregulation of P-glycoprotein (P-gp) expression by PSVII was
      clarified. PSVII significantly suppressed cell proliferation by cell cycle arrest
      in the G0/G1 phase, which was associated with an obvious decrease in cyclin B1/D1
      and CDK2/4/6 protein expression. Moreover, PSVII could attenuate mitochondrial
      membrane potential, increase the expression of apoptosis-related proteins, such
      as Bax and cytochrome c, and decrease the protein expression levels of Bcl-2,
      caspase-9, caspase-3, PARP-1, and p-Akt. We also found that JNK, ERK1/2, and p38
      were regulated by PSVII in K562/ADR cells. And further studies indicated that the
      decrease in the reactive oxygen species level inhibited intrinsic P-gp
      expression. Therefore, PSVII-induced apoptosis in K562/ADR cells was associated
      with Akt/MAPK and the inhibition of P-gp. In addition, PSVII induced a robust
      autophagy in K562/ADR cells as demonstrated by the degradation of LC3-I. These
      results provide a biochemical basis for possible clinical applications of PSVII
      in the treatment of leukemia.

PMID- 29377385
TI  - A massive incorporation of microbial genes into the genome of Tetranychus
      urticae, a polyphagous arthropod herbivore.
AB  - A number of horizontal gene transfers (HGTs) have been identified in the spider
      mite Tetranychus urticae, a chelicerate herbivore. However, the genome of this
      mite species has at present not been thoroughly mined for the presence of HGT
      genes. Here, we performed a systematic screen for HGT genes in the T. urticae
      genome using the h-index metric. Our results not only validated previously
      identified HGT genes but also uncovered 25 novel HGT genes. In addition to HGT
      genes with a predicted biochemical function in carbohydrate, lipid and folate
      metabolism, we also identified the horizontal transfer of a ketopantoate
      hydroxymethyltransferase and a pantoate beta-alanine ligase gene. In plants and
      bacteria, both genes are essential for vitamin B5 biosynthesis and their presence
      in the mite genome strongly suggests that spider mites, similar to Bemisia tabaci
      and nematodes, can synthesize their own vitamin B5. We further show that HGT
      genes were physically embedded within the mite genome and were expressed in
      different life stages. By screening chelicerate genomes and transcriptomes, we
      were able to estimate the evolutionary histories of these HGTs during chelicerate
      evolution. Our study suggests that HGT has made a significant and underestimated
      impact on the metabolic repertoire of plant-feeding spider mites.

PMID- 29377386
TI  - Effect of linkers on immobilization of scFvs with biotin-streptavidin
      interaction.
AB  - Single-chain variable fragment antibodies (scFvs) are attractive for use in
      applications that require high specificity and binding to a target, such as
      biosensors. Previously, we demonstrated that a variety of scFvs can be
      immobilized onto a streptavidin surface through in vivo biotinylation of the
      biotin carboxyl carrier protein (BCCP) or smaller AviTag fused to the scFvs.
      However, the BCCP constructs showed better immobilization than the AviTag
      constructs. In this work, we investigated whether the discrepancy between the
      biotinylation tags could be alleviated by incorporating a flexible (G4 S)n linker
      of varying lengths or a rigid (EA3 K)3 linker between the biotinylation tags and
      the scFvs scFv13R4 and scFv5. Fusion of the (G4 S)5 linker or the (G4 S)3 linker
      to the AviTag construct of scFv13R4 or scFv5, respectively, and fusion of the
      (EA3 K)3 linkers to the AviTag constructs of both scFvs enhanced immobilization.
      Meanwhile, the robust immobilization of the BCCP construct of the scFv constructs
      remained unaffected. The positive to neutral effects of the linkers, with no
      adverse effects, make them beneficial tools to incorporate into fusion proteins
      that show poor immobilization without a linker.

PMID- 29377387
TI  - A qualitative study exploring the views, attitudes and beliefs of patients and
      health professionals towards exercise intervention for people who are surgically
      treated for lung cancer.
AB  - Surgical removal remains the best curative option for patients diagnosed with
      early-stage lung cancer. However, it is also associated with significant
      morbidity and reduced quality of life. Interventions to improve patient outcomes
      are required. This study aimed to explore the views, attitudes and beliefs of key
      stakeholders on exercise intervention for people who are surgically treated for
      lung cancer to inform the development of future interventions. Focus groups and
      individual interviews were carried out at two Scottish sites. The study was
      guided by the Health Action Process Approach behaviour change model. A total of
      23 (12 patients and 11 health professionals) participated in the study. The data
      analysis resulted in three main themes: attitudes and beliefs, external factors
      and intervention design. The results highlighted certain key elements that should
      be included in an exercise intervention, such as the need for supervised
      sessions, an element of individualisation and the perceived social benefits of
      exercising with others. This study emphasises the importance of including key
      stakeholders in the development of complex interventions such as exercise and
      provides important information for the development of future exercise
      intervention trials for people who are surgically treated for lung cancer.

PMID- 29377388
TI  - Indoloazepinone-Constrained Oligomers as Cell-Penetrating and Blood-Brain-Barrier
      Permeating Compounds.
AB  - Non-cationic and amphipathic indoloazepinone-constrained (Aia) oligomers have
      been synthesized as new vectors for intracellular delivery. The conformational
      preferences of the [l-Aia-Xxx]n oligomers were investigated by circular dichroism
      (CD) and NMR spectroscopy. Whereas Boc-[l-Aia-Gly]2,4 -OBn oligomers 12 and 13
      and Boc-[l-Aia-beta3 -h-l-Ala]2,4 -OBn oligomers 16 and 17 were totally or
      partially disordered, Boc-[l-Aia-l-Ala]2 -OBn (14) induced a typical turn
      stabilized by C5 - and C7 -membered H-bond pseudo-cycles and aromatic
      interactions. Boc-[l-Aia-l-Ala]4 -OBn (15) exhibited a unique structure with
      remarkable T-shaped pi-stacking interactions involving the indole rings of the
      four l-Aia residues forming a dense hydrophobic cluster. All of the proposed FITC
      6-Ahx-[l-Aia-Xxx]4 -NH2 oligomers 19-23, with the exception of FITC-6-Ahx-[l-Aia
      Gly]4 -NH2 (18), were internalized by MDA-MB-231 cells with higher efficiency
      than the positive references penetratin and Arg8 . In parallel, the compounds of
      this series were successfully explored in an in vitro blood-brain barrier (BBB)
      permeation assay. Although no passive diffusion permeability was observed for any
      of the tested Ac-[l-Aia-Xxx]4 -NH2 oligomers in the PAMPA model, Ac-[l-Aia-l
      Arg]4 -NH2 (26) showed significant permeation in the in vitro cell-based human
      model of the BBB, suggesting an active mechanism of cell penetration.

PMID- 29377389
TI  - Modified methylated DNA immunoprecipitation protocol for noninvasive prenatal
      diagnosis of Down syndrome.
AB  - AIM: Methylated DNA immunoprecipitation real-time quantitative polymerase chain
      reaction (MeDIP-real-time qPCR) has been introduced as noninvasive prenatal test
      that has shown absolute detection rate in the screening of Down syndrome. Herein,
      we aimed to propose a novel modification of MeDIP-qPCR and assess its potential
      to alleviate the overall cost of the test, being used in very early weeks of
      pregnancy, and develop it to a noninvasive prenatal diagnosis biosensor in future
      researches. METHODS: Cell-free fetal DNA (cffDNA) isolated from 60 pregnant
      women, including 29 normal and 31 trisomy 21 pregnancies, were analyzed using
      proposed MeDIP protocol. Enriched methylated DNA sequences were amplified through
      real-time qPCR using eight fetal-specific primer pairs. The status of samples was
      determined through the calculation of D-value with the cutoff point of zero.
      RESULTS: The sensitivity and specificity of the MeDIP protocols using
      nanoparticles were 100% and 100%, respectively. CONCLUSION: Remarkable decrease
      in the price of MeDIP test per each patient would be a reasonable factor to
      confirm it on larger sample size. Moreover, the high detection rate of screening
      and the availability of the required instruments around the world make
      satisfactory reasons to be tested in earlier weeks of pregnancy, thanks to the
      high sensitivity of gold shell nanoparticles.

PMID- 29377390
TI  - Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the
      endocrine system and social behaviours.
AB  - Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III
      mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and
      localised to presynaptic active zones of the mammalian central nervous system. We
      previously reported that mGluR7 is essential for intermale aggression and
      amygdala-dependent fear learning. To elucidate the role of mGluR7 in the
      neuroendocrine system, we performed biochemical analyses and found a significant
      reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone
      replacement restored intermale aggressive behaviour in castrated wild-type mice
      to the level of gonadally intact wild-type mice. However, given the same dosage
      of testosterone replacement, mGluR7 KO mice showed almost no aggressive
      behaviour. These results indicate that reduction of plasma testosterone is
      unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social
      investigating behaviour of intact mGluR7 KO mice also differed from that of wild
      type mice; e.g. the KO mice showing less frequent anogenital sniffing and more
      frequent grooming behaviour. Testosterone replacement increased anogenital
      sniffing and grooming behaviour in castrated mGluR7 KO mice, while the
      differences were still present between castrated wild-type mice and KO mice after
      both underwent testosterone replacement. These results imply that reduction of
      plasma testosterone may partially inhibit social investigating behaviours in
      intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal
      vesicles than those of castrated wild-type mice, although seminal vesicle weights
      were normal in intact mice. These observations suggest that, besides testicular
      testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice,
      and indicate a critical role of mGluR7 in the endocrine system. Taken together,
      our findings demonstrate that mGluR7 is essential for the regulation of the
      endocrine system, in addition to innate behaviours such as intermale aggression
      and fear response.

PMID- 29377391
TI  - Risk analysis of malignant potential of oral verrucous hyperplasia: A follow-up
      study of 269 patients and copy number variation analysis.
AB  - BACKGROUND: Oral verrucous hyperplasia is commonly observed in the oral cavity of
      betel quid chewers and is a potential malignant disorder. However, the prognostic
      factors and genetic alterations of oral verrucous hyperplasia are unclear.
      METHODS: We calculate the survival rate and prognostic factors using a Kaplan
      Meier analysis and Cox proportional hazards regression model. Copy number
      variations were analyzed using a single-nucleotide polymorphism (SNP) array.
      RESULTS: The 5-year disease-free and cancer-free survival rates of patients with
      oral verrucous hyperplasia were approximately 40% and 70%, respectively. Heavy
      betel quid chewing, advanced oral submucous fibrosis, and nonbuccal and nontongue
      lesions were risk factors for malignant transformation, whereas dysplasia did not
      affect outcomes. The gene amplification of CTTN, FOLR3, ORAOV1, PPFIA1, and
      RNF121 were associated with the poor prognosis of oral verrucous hyperplasia.
      CONCLUSION: Heavy betel quid chewing, advanced oral submucous fibrosis, and
      nonbuccal and nontongue lesions are high-risk factors of patients with oral
      verrucous hyperplasia. The 5-copy number variation-associated genes could be used
      for early diagnosis and predicting the prognosis.

PMID- 29377392
TI  - Chronic intermittent hypoxia and renovascular hypertension: A case of one plus
      one equals one-half!

PMID- 29377393
TI  - Catalytic CO Oxidation by O2 Mediated by Noble-Metal-Free Cluster Anions Cu2 VO3
      5.
AB  - Catalytic CO oxidation by molecular O2 is an important model reaction in both the
      condensed phase and gas-phase studies. Available gas-phase studies indicate that
      noble metal is indispensable in catalytic CO oxidation by O2 under thermal
      collision conditions. Herein, we identified the first example of noble-metal-free
      heteronuclear oxide cluster catalysts, the copper-vanadium bimetallic oxide
      clusters Cu2 VO3-5- for CO oxidation by O2 . The reactions were characterized by
      mass spectrometry, photoelectron spectroscopy, and density functional
      calculations. The dynamic nature of the Cu-Cu unit in terms of the electron
      storage and release is the driving force to promote CO oxidation and O2
      activation during the catalysis.

PMID- 29377394
TI  - Platelet-predominate gene expression and reticulated platelets in nonvalvular
      atrial fibrillation: Effect of pulmonary veins isolation.
AB  - INTRODUCTION: Reticulated platelet (RP) content is increased in nonvalvular
      atrial fibrillation (NVAF). The purpose of this study was to determine if
      platelet content, morphology, and RP proportion are modulated by platelet genes.
      METHODS AND RESULTS: Expression of six platelet-predominate genes impacting
      platelet formation and release, platelet count, and RP content was assessed in
      NVAF patients before and 3-4 months after pulmonary veins isolation (PVI) and
      compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was
      reverse-transcribed assayed against selected genes utilizing real-time qPCR, and
      expressed as mean cycle threshold (DeltaCt) using beta-2-microglobulin as
      endogenous control. RP content was assessed by flow cytometry. A fourfold lower
      expression of CFL1 gene coding for nonmuscle cofilin (7.8 +/- 0.9 vs. 5.7 +/-
      1.6, P < 0.001) and twofold lower expression of four other genes were associated
      with similar platelet counts but fourfold higher (28.7+7.0 vs. 6.7+5.4, P <
      0.001) RP content (%) in 97 NVAF cases compared to 51 NSR controls. Three to 4
      months after PVI, RP decreased by 28%, while CFL1 gene expression increased over
      twofold but TUBA4A gene expression decreased almost twofold; NFE2 and MYL6 gene
      expression remained unchanged. CONCLUSIONS: NVAF is associated with notable
      downregulation of genes directing platelet production and size but increased RP
      content. PVI impacts the expression of many of these genes, implying a direct
      relationship between atrial fibrillation and platelet biogenesis.

PMID- 29377395
TI  - Atopic dermatitis and alcohol use - a meta-analysis and systematic review.
AB  - While several maternal exposures have been associated with an increased risk of
      atopic dermatitis (AD) in offspring, the effect of alcohol use during pregnancy
      on the risk of AD in offspring is unclear. Furthermore, it is unclear whether
      adults with AD have an increased alcohol use, although other poor health
      behaviours have been associated with AD including smoking and physical inactivity
      as well as psychiatric disease. In this systematic review and meta-analysis, the
      association between alcohol use and AD was investigated in two ways: 1) whether
      alcohol use (drinkers versus abstainers) during pregnancy is associated with AD
      in offspring and 2) whether AD is associated with increased alcohol use. The
      medical databases PubMed, EMBASE and Web of Science were searched, and data
      extraction was carried out by two independent reviewers. Eighteen studies were
      included in the qualitative analysis (comparing alcohol drinkers to abstainers),
      and 12 studies were included in the quantitative analysis. There was a positive
      association between alcohol use during pregnancy and development of AD in
      offspring (pooled odds ratio [OR] 1.16; 95% confidence interval [CI] 1.09-1.24).
      However, there was no consistent association between AD in adults and adolescents
      and alcohol use (pooled OR 1.06; 95% CI 0.92-1.23). There is a need for future
      well-designed prospective studies to firmly establish the association between
      alcohol use and AD.

PMID- 29377396
TI  - RBC alloantibody prevalence and specificity in a Western Norwegian tertiary
      hospital.
AB  - BACKGROUND AND OBJECTIVE: Although several studies focus on red blood cell (RBC)
      alloantibody distribution in selected patient populations, few address the
      specificity and frequency in all relevant groups. This study reports alloantibody
      frequency, distribution and the relationship to age and gender in blood donors,
      pregnant women and potential recipients of blood products. METHODS: This
      historical cohort study included 55 462 consecutive antibody screening tests from
      a tertiary Western Norwegian Hospital. Descriptive statistics were performed, and
      the results were compared with the literature. RESULTS: The detection and
      immunisation frequency for the whole cohort were 0.39 and 0.51%, respectively,
      whereas the RBC alloantibody prevalence was 0.73%. The most frequent RBC
      alloantibodies were anti-E (20.1%), anti-M (18.7%), anti-K (9.8%), anti-D (8.9%)
      and anti-Fy(a) (7.0%). In pregnant women, the most frequent RBC alloantibodies
      were anti-M, anti-D and anti-Le(a) (20.8, 18.9 and 18.9%, respectively), whereas
      there was no anti-K detected. Anti-E and anti-M were the dominating RBC
      alloantibodies in the pre-transfusion testing of in-hospital patients (24.1 and
      17.1%, respectively). Eighteen (9.2%) persons in the total cohort had two RBC
      alloantibodies, six persons had three alloantibodies, and two persons had four
      alloantibodies. Rh and K typing to prevent future immunisations was only
      performed in 21.0% of the individuals who presented with a new alloantibody;
      despite that, 50.5% of the detected alloantibodies had such specificities.
      CONCLUSIONS: The immunisation frequency and the level of anti-K are low compared
      to national and international studies. Rh and K phenotype-matched blood
      transfusions might be a feasible future strategy to further decrease RBC
      alloantibodies.

PMID- 29377397
TI  - Comparison of two kinds of skin imaging analysis software: VISIA(r) from Canfield
      and IPP(r) from Media Cybernetics.
AB  - BACKGROUND: Skin imaging analysis, acting as a supplement to noninvasive
      bioengineering devices, has been widely used in medical cosmetology and cosmetic
      product evaluation. The main aim of this study is to assess the differences and
      correlations in measuring skin spots, wrinkles, vascular features, porphyrin, and
      pore between two commercially available image analysis software. MATERIALS AND
      METHODS: Seventy healthy women were included in the study. Before taking
      pictures, the dermatologist evaluated subjects' skin conditions. Test sites
      included the forehead, cheek, and periorbital skin. A 2 * 2 cm cardboard was used
      to make a mark on the skin surface. Pictures were taken using VISIA(r) under
      three kinds light conditions and analyzed using VISIA(r) and IPP(r) respectively.
      RESULTS: (1) Skin pore, red area, ultraviolet spot, brown spot, porphyrin, and
      wrinkle measured with VISIA(r) were correlated with those measured with IPP(r) (P
      < .01). (2) Spot, wrinkle, fine line, brown spot, and red area analyzed with
      VISIA(r) were correlated with age on the forehead and periorbital skin (P < .05).
      L-value, Crow's feet, ultraviolet spot, brown spot, and red area analyzed with
      IPP(r) were correlated with age on the periorbital skin (P < .05). (3) L-value,
      spot, wrinkle, fine line, porphyrin, red area, and pore analyzed with VISIA(r)
      and IPP(r) showed correlations with the subjective evaluation scores (P < .05).
      CONCLUSIONS: VISIA(r) and IPP(r) showed acceptable correlation in measuring
      various skin conditions. VISIA(r) showed a high sensibility when measured on the
      forehead skin. IPP(r) is available as an alternative software program to evaluate
      skin features.

PMID- 29377399
TI  - A systematic review of pyoderma gangrenosum with pulmonary involvement: clinical
      presentation, diagnosis and management.

PMID- 29377398
TI  - Lipid rafts can form in the inner and outer membranes of Borrelia burgdorferi and
      have different properties and associated proteins.
AB  - Lipid rafts are microdomains present in the membrane of eukaryotic organisms and
      bacterial pathogens. They are characterized by having tightly packed lipids and a
      subset of specific proteins. Lipid rafts are associated with a variety of
      important biological processes including signaling and lateral sorting of
      proteins. To determine whether lipid rafts exist in the inner membrane of
      Borrelia burgdorferi, we separated the inner and outer membranes and analyzed the
      lipid constituents present in each membrane fraction. We found that both the
      inner and outer membranes have cholesterol and cholesterol glycolipids.
      Fluorescence anisotropy and FRET showed that lipids from both membranes can form
      rafts but have different abilities to do so. The analysis of the biochemically
      defined proteome of lipid rafts from the inner membrane revealed a diverse set of
      proteins, different from those associated with the outer membrane, with functions
      in protein trafficking, chemotaxis and signaling.

PMID- 29377400
TI  - Injuries in Dutch elite field hockey players: A prospective cohort study.
AB  - This study describes the prevalence, incidence density, severity, and nature of
      injuries in elite field hockey players over the Dutch 2015-2016 season. Eighty
      players answered a baseline questionnaire and were subsequently followed up every
      2 weeks to report the hours spent on training/competition and experienced
      injuries, which were registered using the Oslo Sports Trauma Research Centre
      Questionnaire on Health Problems. Of the 74 players included in the analysis, 52
      (70%) reported 112 injuries. Eighty-seven injuries (78%) received medical
      attention, and 56 (50%) led to training/competition time-loss. Thirty-four
      injuries (30%) hampered players' availability to train and compete. Most of the
      injuries (74%) were not caused by any contact. The mean prevalence of injury was
      29% (95% confidence interval [CI] 3-55) for all, 9% (95% CI 0-20) for acute, and
      14% (95% CI 0-36) for overuse injuries. Players sustained 3.5 (95% CI 2.5-4.5)
      new acute injuries per 1000 hours of training and 12.3 (95% CI 7.6-17.0) per 1000
      hours of competition. The median of the severity score was 28 from 100 (25%-75%
      interquartile range [IQR] 16-42) for all, 35 (IQR 23-53) for acute, and 21 (IQR
      16-31) for overuse injuries. On average, 1 in 4 elite field hockey players
      experiences an injury within a 2-week period during the season. Although acute
      injuries are common, overuse injuries pose a comparable problem in elite field
      hockey. As injuries are a burden on players' health and may hamper performance
      and availability to train and compete, prevention is of great importance.

PMID- 29377401
TI  - Increased expression of TREM2 in peripheral cells from mild cognitive impairment
      patients who progress into Alzheimer's disease.
AB  - BACKGROUND AND PURPOSE: Neuroinflammation plays a role in the aetiopathogenesis
      of Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2
      (TREM2), a cell surface receptor of the immunoglobulin superfamily, seems to have
      protective anti-inflammatory activity in AD. METHODS: Triggering receptor
      expressed on myeloid cells 2 expression was analysed in peripheral blood
      mononuclear cells from healthy subjects (CT) and from patients with either AD or
      mild cognitive impairment (MCI). MCI patients were re-evaluated at a 2-year
      follow-up to investigate their progression to AD (MCI-AD) or lack thereof (MCI
      MCI). RESULTS: Triggering receptor expressed on myeloid cells 2 gene expression
      was higher in AD than CT patients, but was highest in MCI. At recruitment TREM2
      levels were higher in MCI-AD than in MCI-MCI, and in MCI-AD were higher initially
      than at follow-up. TREM2 displayed a moderate degree of sensitivity and
      specificity for identifying MCI-AD in all MCI patients. Our data showed higher
      TREM2 levels in allele epsilon4 of apolipoprotein E (ApoE epsilon4) carriers than
      non-carriers in MCI and particularly in MCI-AD. CONCLUSIONS: These data seem to
      confirm the protective role of TREM2 in the pre-clinical stage of AD.
      Upregulation of TREM2 in MCI-AD could be a mechanism to counteract the activation
      of neuroinflammatory processes. It is possible that TREM2 and ApoE epsilon4
      interact synergistically in the pre-clinical stage of AD. Therefore, TREM2 may be
      useful as an early peripheral biomarker for the development of AD.

PMID- 29377402
TI  - Infection transmission among lung transplant couples.
AB  - The risk of transmission of infections in partnerships between 2 transplant
      recipients is unknown. The aim of this study was to evaluate transmission in such
      couples. In this single-center study, lung transplant (LTx) couples were
      identified among outpatients between 1988 and 2016. Infection rates per year and
      survival were compared to matched LTx-recipients not living in a transplant
      partnership. Twelve transplant couples were analyzed with cumulative 65 years of
      relationship. Overall infections were similar between LTx-couples and matched LTx
      patients. No significant differences were noted in bacterial infections (.12 vs
      .27 per year), community-acquired viral (CARV) infections (.26 vs .22 per year),
      rejection treatments (.22 vs .12 per year), or hospitalizations (.26 vs .46 per
      year) in transplant couples and matched controls, respectively. There was no
      transmission of any microbial colonization from 1 partner to the other. Five
      cases of simultaneously detected CARV infections occurred (metapneumovirus [3],
      H1N1 [1], and respiratory syncytial virus [RSV; 1]). Three couples exhibited
      cytomegalovirus (CMV) reactivation in both partners at the same time with
      confirmed seronegativity before transplantation. In this case series of 12 lung
      transplant couples, the partnerships between 2 transplant recipients have no
      greater risk of bacterial infection and colonization transmission in comparison
      with recipients not living in a transplant relationship. However, transplant
      couples should be informed about the risk for transmission of viral infections,
      which could impact the development of chronic lung allograft dysfunction (CLAD).

PMID- 29377403
TI  - Silica-Supported Pentamethylcyclopentadienyl Ytterbium(II) and Samarium(II)
      Sites: Ultrahigh Molecular Weight Polyethylene without Co-Catalyst.
AB  - Designing highly active supported ethylene polymerization catalysts that do not
      require a co-catalyst to generate electrophilic metal alkyl species is still a
      challenge despite its industrial relevance. Described herein is the synthesis and
      characterization of well-defined silica-supported cyclopentadienyl LnII sites
      (Ln=Yb and Sm) of general formula [(=SiO)LnCp*]. These well-defined surface
      species are highly activite towards ethylene polymerization in the absence of
      added co-catalyst. Initiation is proposed to occur by single electron transfer.

PMID- 29377404
TI  - Sedation for magnetic resonance imaging using propofol with or without ketamine
      at induction in pediatrics-A prospective randomized double-blinded study.
AB  - INTRODUCTION: Deep sedation using propofol has become a standard technique in
      children. This double-blinded randomized clinical trial aims to compare the
      clinical effects of propofol-mono-sedation vs a combination of propofol and
      ketamine at induction and a reduced propofol infusion rate for maintenance in
      children undergoing diagnostic magnetic resonance imaging. METHODS: Children aged
      from 3 months to 10 years scheduled as outpatients for elective magnetic
      resonance imaging with deep sedation were included. They were randomized into 2
      groups, receiving either 1 mg/kg ketamine at induction, then a propofol infusion
      rate of 5 mg/kg/h or a propofol infusion rate of 10 mg/kg/h without prior
      ketamine. Time to full recovery (modified Aldrete score = 10) was the primary
      outcome. Further outcomes were quality of induction, immobilization during image
      acquisition, recovery, postoperative nausea and vomiting, emergence delirium
      using the Pediatric Anesthesia Emergence Delirium scale, vital signs and adverse
      cardiorespiratory events. All patients and parents as well as anesthetists,
      imaging technicians, and postsedation personnel were blinded. Data are given as
      median (range). RESULTS: In total, 347 children aged 4.0 (0.25-10.9) years,
      weighing 15.6 (5.3-54) kg, ASA classification I, II, or III (141/188/18) were
      included. The ketamine-propofol group showed significantly shorter recovery times
      (38 (22-65) vs 54 (37-77) minutes; median difference 14 (95% CI: 8, 20) minutes;
      P < .001), better quality of induction, and higher blood pressure, but higher
      incidence of movement requiring additional sedative drugs. There were no
      significant differences in respiratory side effects, cardiovascular compromise,
      emergence delirium, or postoperative nausea and vomiting. CONCLUSION: Both
      sedation concepts proved to be reliable with a low incidence of side effects.
      Ketamine at induction with a reduced propofol infusion rate leads to faster
      postanesthetic recovery.

PMID- 29377405
TI  - How should contact force be used for catheter ablation of atrial fibrillation?

PMID- 29377406
TI  - Regulation of bone blood flow in humans: The role of nitric oxide,
      prostaglandins, and adenosine.
AB  - The mechanisms that regulate bone blood flow (BBF) in humans are largely unknown.
      Animal studies suggest that nitric oxide (NO) could be involved, and in this
      study, we investigated the effects of inhibition of nitric oxide synthase (NOS)
      alone and in combination with inhibition of cyclooxygenase (COX) enzyme, thus
      prostaglandin (PG) synthesis on femoral bone marrow blood flow by positron
      emission tomography in healthy young men at rest and during one-leg dynamic
      exercise. In an additional group of healthy men, the role of adenosine (ADO) in
      the regulation of BBF during exercise was investigated by use of an adenosine
      receptor blocker (aminophylline). Inhibitors were directly infused into the
      femoral artery. Resting BBF was 1.1 +/- 0.4 mL 100 g-1 min-1 and increased to
      almost sixfold in response to exercise (6.3 +/- 1.5 mL 100 g-1  min-1 ).
      Inhibition of NOS reduced BBF at rest to 0.7 +/- 0.3 mL 100 g-1  min-1 (P =
      .036), but did not affect BBF significantly during exercise (5.5 +/- 1.4 mL 100 g
      1  min-1 , P = .25). On the other hand, while combined NOS and COX inhibition did
      not cause any further reduction of blood flow at rest (0.6 +/- 0.2 mL 100 g-1 min
      1 ), the combined blockade reduced BBF during exercise by ~21%, to 5.0 +/- 1.8 mL
      100 g-1  min-1 (P = .014). Finally, the ADO inhibition during exercise reduced
      BBF from 5.5 +/- 1.9 mL 100 g-1  min-1 to 4.6 +/- 1.2 mL 100 g-1  min-1 (P =
      .045). In conclusion, our results support the view that NO is involved in
      controlling bone marrow blood flow at rest, and NO, PG, and ADO play important
      roles in controlling human BBF during exercise.

PMID- 29377407
TI  - Assertiveness of meat-borne Lactococcus piscium strains and their potential for
      competitive exclusion of spoilage bacteria in situ and in vitro.
AB  - AIMS: This study aimed to investigate intraspecies assertiveness of meat-borne
      Lactococcus piscium isolates, inhibitory effects on unwanted and harmful meat
      spoilers, and the prevalence on beef deliberately inoculated with Lc. piscium.
      METHODS AND RESULTS: Co-inoculation of Lc. piscium isolates and spoilers
      (Brochothrix thermosphacta, Leuconostoc gelidum subsp. gasicomitatum,
      Carnobacterium divergens, Pseudomonas weihenstephanensis, Serratia liquefaciens,
      Hafnia alvei) were conducted in sterile meat simulation medium. Differentiation
      of Lc. piscium strains was carried out with colony-based RAPD-PCR. Selective
      cultivation was used to differentiate spoilers from Lc. piscium. Intraspecies
      assertiveness revealed Lc. piscium TMW2.1614 as most assertive strain. Co
      inoculation of selected Lc. piscium strains caused substantial growth reduction
      of spoilers while the extent was strain- and spoiler dependent. Monitoring the
      microbiota on beef steaks deliberately inoculated with Lc. piscium revealed
      prevalence over the endogenous microbiota while maintaining a ripened sensory
      impression without undesired alterations. CONCLUSIONS: This study reveals Lc.
      piscium strains TMW2.1612/2.1614/2.1615 as highly competitive against spoilers in
      vitro while beef deliberately inoculated with these strains maintained acceptable
      organoleptics. SIGNIFICANCE AND IMPACT OF THE STUDY: Selected Lc. piscium strains
      exhibit high potential for application as bioprotective cultures for competitive
      exclusion on beef in order to extend minimum shelf life and enhance product
      safety of meat.

PMID- 29377408
TI  - Two-year trial of intermittent insulin therapy vs metformin for the preservation
      of beta-cell function after initial short-term intensive insulin induction in
      early type 2 diabetes.
AB  - AIMS: To test the hypothesis that "induction" intensive insulin therapy (IIT)
      needs to be followed by "maintenance therapy" to preserve beta-cell function, and
      to evaluate the impact on beta-cell function over 2 years of two approaches to
      maintenance therapy: intermittent short-term IIT every 3 months vs daily
      metformin. MATERIALS AND METHODS: In this trial, 24 adults with a mean type 2
      diabetes mellitus (T2DM) duration of 2.0 +/- 1.7 years and glycated haemoglobin
      (HbA1c) levels 6.4 +/- 0.1% (46 +/- 1.1mmol/mol) were randomized to 3 weeks of
      induction IIT (glargine, lispro) followed by either repeat IIT for up to 2 weeks
      every 3 months or daily metformin. Participants underwent serial assessment of
      beta-cell function using the Insulin Secretion-Sensitivity Index-2 (ISSI-2) on an
      oral glucose tolerance test every 3 months. RESULTS: The primary outcome of
      baseline-adjusted ISSI-2 at 2 years was higher in the metformin arm compared with
      intermittent IIT (245.0 +/- 31.7 vs 142.2 +/- 18.4; P = .008). Baseline-adjusted
      HbA1c at 2 years (secondary outcome) was lower in the metformin arm (6.0 +/- 0.2%
      vs 7.3 +/- 0.2%; P = .0006) (42 +/- 2.2 vs 56 +/- 2.2mmol/mol). At study
      completion, 66.7% of participants randomized to metformin had an HbA1c
      concentration <= 6.0% (<=42mmol/mol), compared with 8.3% of those on intermittent
      IIT (P = .009). There were no differences in insulin sensitivity. CONCLUSION:
      After induction IIT, metformin was superior to intermittent IIT for maintaining
      beta-cell function and glycaemic control over 2 years. The strategy of induction
      and maintenance therapy to preserve beta-cell function warrants exploration in
      early T2DM.

PMID- 29377409
TI  - Diminishing benefit of smoking cessation medications during the first year: a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND AND AIMS: Although smoking cessation medications have shown
      effectiveness in increasing abstinence in randomized controlled trials (RCTs), it
      is unclear to what extent benefits persist over time. This paper assesses whether
      the benefits of smoking cessation medications decline over the first year.
      METHODS: We selected studies from three systematic reviews published by the
      Cochrane Collaboration. RCTs of first-line smoking cessation medications, with 6-
      and 12-month follow-up, were eligible for inclusion. Meta-analysis was used to
      synthesize information on sustained abstinence (SA) at 6 versus 12 months and 3
      versus 6 months, using the risk difference (RD) ('net benefit') between
      intervention and control group quit rates, the relative risk (RR) and the odds
      ratio (OR). RESULTS: Sixty-one studies (27 647 participants) were included. Fewer
      than 40% of intervention group participants were sustained abstinent at 3 months
      (bupropion: 37.1%; nicotine replacement therapy (NRT): 34.8%; varenicline:
      39.3%); approximately a quarter were sustained abstinent at 6 months (bupropion:
      25.9%; NRT: 26.6%; varenicline: 25.4%), and approximately a fifth were sustained
      abstinent at 12 months (bupropion: 19.9%; NRT: 19.8%%; varenicline: 18.7%). There
      was only a small decline in RR (3 months: 1.95 [95% confidence interval (CI) =
      1.74-2.18, P < 0.0001]; 6 months: 1.87 (95% CI = 1.67-2.08 P < 0.0001); 12
      months: 1.75 (95% CI = 1.56-1.95, P < 0.0001) between intervention and control
      groups over time, but a substantial decline in net benefit [3 months: RD = 17.3%
      (14.5-20.1%); 6 months: RD = 11.8% (10.0-13.7%); 12 months: RD = 8.2% (6.8
      9.6%)]. The decline in net benefit was statistically significant between 3 and 6
      [RD = 4.95% (95% CI = 3.49-6.41%), P < 0.0001] and 6 and 12 months [RD = 3.00%
      (95% CI = 2.36%-3.64%), P < 0.0001)] for medications combined and individual
      medications. CONCLUSIONS: The proportion of smokers who use smoking cessation
      medications who benefit from doing so decreases during the course of the first
      year, but a net benefit still remains at 12 months.

PMID- 29377411
TI  - Wait-list mortality of young patients with Biliary atresia: Competing risk
      analysis of a eurotransplant registry-based cohort.
AB  - Liver transplantation (LT) is the standard treatment for biliary atresia (BA)
      patients with end-stage liver disease. The prognosis after LT has steadily
      improved, but overall prognosis of BA patients is also determined by mortality
      before LT. We aimed to quantify mortality in young BA patients on the
      Eurotransplant waiting list and to determine the effect of disease severity and
      age at time of listing on pretransplant mortality. We used a cohort study design,
      which incorporated data from the Eurotransplant registry. Participants were 711
      BA patients who were below 5 years of age from 5 countries and listed for LT
      between 2001 and 2014. We applied a competing risk analysis to evaluate
      simultaneously the outcomes death, LT, and still waiting for a suitable organ. We
      used Cox proportional hazards regression to assess 2-year mortality. In a
      subcohort of 416 children, we performed multivariate analyses between 2-year
      mortality and disease severity or age, each at listing. Disease severity at
      listing was quantified by the Model for End-Stage Liver Disease (MELD) score,
      which assesses bilirubin, creatinine, albumin, and international normalized ratio
      as continuous variables. Two-year wait-list mortality was 7.9%. Age below 6
      months and MELD score above 20 points, each at listing, were strongly and
      independently associated with 2-year mortality (each P < 0.001). A total of 21%
      of infants who fulfilled both criteria did not survive the first 6 months on the
      waiting list. In conclusion, our findings quantify mortality among young BA
      patients on the waiting list and the relative importance of risk factors (age and
      severity of disease at listing). Our results provide both an evidence base to
      rationally address high mortality in subgroups and a methodology to assess
      effects of implemented changes, for example, in allocation rules. Liver
      Transplantation 24 810-819 2018 AASLD.

PMID- 29377410
TI  - Inhibition of Aldehyde Dehydrogenase-Activity Expands Multipotent Myeloid
      Progenitor Cells with Vascular Regenerative Function.
AB  - Blood-derived progenitor cell transplantation holds potential for the treatment
      of severe vascular diseases. Human umbilical cord blood (UCB)-derived
      hematopoietic progenitor cells purified using high aldehyde dehydrogenase (ALDHhi
      ) activity demonstrate pro-angiogenic functions following intramuscular (i.m.)
      transplantation into immunodeficient mice with hind-limb ischemia. Unfortunately,
      UCB ALDHhi cells are rare and prolonged ex vivo expansion leads to loss of high
      ALDH-activity and diminished vascular regenerative function. ALDH-activity
      generates retinoic acid, a potent driver of hematopoietic differentiation,
      creating a paradoxical challenge to expand UCB ALDHhi cells while limiting
      differentiation and retaining pro-angiogenic functions. We investigated whether
      inhibition of ALDH-activity during ex vivo expansion of UCB ALDHhi cells would
      prevent differentiation and expand progeny that retained pro-angiogenic functions
      after transplantation into non-obese diabetic/severe combined immunodeficient
      mice with femoral artery ligation-induced unilateral hind-limb ischemia. Human
      UCB ALDHhi cells were cultured under serum-free conditions for 9 days, with or
      without the reversible ALDH-inhibitor, diethylaminobenzaldehyde (DEAB). Although
      total cell numbers were increased >70-fold, the frequency of cells that retained
      ALDHhi /CD34+ phenotype was significantly diminished under basal conditions. In
      contrast, DEAB-inhibition increased total ALDHhi /CD34+ cell number by >=10-fold,
      reduced differentiation marker (CD38) expression, and enhanced the retention of
      multipotent colony-forming cells in vitro. Proteomic analysis revealed that DEAB
      treated cells upregulated anti-apoptotic protein expression and diminished
      production of proteins implicated with megakaryocyte differentiation. The i.m.
      transplantation of DEAB-treated cells into mice with hind-limb ischemia
      stimulated endothelial cell proliferation and augmented recovery of hind-limb
      perfusion. DEAB-inhibition of ALDH-activity delayed hematopoietic differentiation
      and expanded multipotent myeloid cells that accelerated vascular regeneration
      following i.m. transplantation in vivo. Stem Cells 2018;36:723-736.

PMID- 29377412
TI  - High-fat diet induces a neurometabolic state characterized by changes in
      glutamate and N-acetylaspartate pools associated with early glucose intolerance:
      An in vivo multimodal MRI study.
AB  - BACKGROUND: Type-2 diabetes mellitus (T2DM) is a metabolic disorder with a broad
      range of complications in the brain that depend on the conditions that precede
      its onset, such as obesity and metabolic syndromes. It has been suggested that
      neurotransmitter and metabolic perturbations may emerge even before the early
      stages of T2DM and that high-caloric intake could adversely influence the brain
      in such states. Notwithstanding, evidence for neurochemical and structural
      alterations in these conditions are still sparse and controversial. PURPOSE: To
      evaluate the influence of high-fat diet in the neurochemical profile and
      structural integrity of the rodent brain. STUDY TYPE: Prospective. SUBJECTS:
      Wistar rats (n = 12/group). FIELD STRENGTH/SEQUENCE: A PRESS, ISIS, RARE, and EPI
      sequences were performed at 9.4T. ASSESSMENT: Neurochemical and structural
      parameters were assessed by magnetic resonance spectroscopy, voxel-based
      morphometry, volumetry, and diffusion tensor imaging. STATISTICAL TESTS:
      Measurements were compared through Student and Mann-Whitney tests. Pearson
      correlation was used to assess relationships between parameters. RESULTS: Animals
      submitted to high-caloric intake gained weight (P = 0.003) and developed glucose
      intolerance (P < 0.001) but not hyperglycemia. In the hippocampus, the diet
      induced perturbations in glutamatergic metabolites reflected by increased levels
      of glutamine (P = 0.016) and glutamatergic pool (Glx) (P = 0.036), which were
      negatively correlated with glucose intolerance (glutamine, r = -0.804, P =
      0.029), suggesting a link with neurometabolic dysregulation. At caudate-putamen,
      high-fat diet led to a surprising increase in the pool of N-acetylaspartate (P =
      0.028). A relation with metabolic changes was again suggested by the negative
      correlation between glucose intolerance and levels of glutamatergic metabolites
      in this region (glutamate, r = -0.845, P = 0.014; Glx, r = -0.834, P = 0.020).
      Neither changes in phosphate compounds nor major structural alterations were
      observed for both regions. DATA CONCLUSION: We found evidence that high-fat diet
      induced obesity leads to distinct early and region-specific
      metabolic/neurochemical imbalances in the presence of early glucose intolerance
      even when structural alterations or T2DM are absent. LEVEL OF EVIDENCE: 1
      Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018.

PMID- 29377413
TI  - Assessment of the general quality of sunscreen products available in Palestine
      and method verification of the sun protection factor using Food and Drug
      Administration guidelines.
AB  - BACKGROUND: Sunlight exposure affects all skin types causing skin tanning, burns
      or even skin cancer. Sunscreens were invented to prevent these outcomes by
      scattering or absorbing the UV light. AIMS: This study aimed to verify the
      effectiveness of Mansur method in SPF measurement and to find out how much
      reliable the labeled sun protection factor (SPF) value for the products that are
      imported to Palestine knowing that they are considered as cosmetics and they
      don't undergo tests by the Ministry Of Health (MOH). MATERIALS: In this research,
      sun protection factor (SPF) was determined for 16 commercially available
      sunscreen products using Mansur equation which was also validated; moreover
      sunscreen classification, product phase determination and pH measurement were
      also done. RESULTS: Sun protection factor values were mostly 50, 43.75% of the
      analyzed samples were close to the labeled SPF, 31.25% were under the labeled
      value, and 25% SPF value above the labeled value. All samples exhibited a pH
      close to skin pH. 62% of them were found to be O/W. Cosmetic companies and
      importers should focus on pediatric sunscreens, since only 12.5% are pediatric
      sunscreens. CONCLUSIONS: Ministry Of Health should ask prove about the quality of
      an SPF value of sunscreens for final registration of these products. More
      instructions should be available on the label regarding the proper use
      especially, if they are not water proof.

PMID- 29377414
TI  - Optical clearing agent reduces scattering of light by the stratum corneum and
      modulates the physical properties of coenocytes via hydration.
AB  - BACKGROUND: The interaction between light and the skin determine how the skin
      looks to the human eye. Light can be absorbed, scattered, and reflected by
      different components of the skin in a variety of different ways. Here, we focus
      on the scattering properties of the outmost layer, the stratum corneum (SC).
      However, we currently have limited methods with which to distinguish the
      scattering of light by SC from the changes due to other components of the skin.
      MATERIALS AND METHODS: Dark-field images of tape-striped corneocytes were used in
      vitro to study the differences in light scattered by the SC and other skin
      components. Several optical clearing agents (OCAs) were tested for their ability
      to reduce light scattering. Physical properties of the SC (water content, keratin
      configuration, and volume) after OCA treatment were investigated using FT-IR,
      confocal Raman microscopy, and 3D laser microscopy. RESULTS: Urea derivatives,
      several reducing sugars, and sugar alcohols, which were used as OCA in optics and
      also used as humectants in cosmetic area, could reduce scattering. However,
      unlike dehydration in optics, penetration of water into the keratin was increased
      at low OCA concentrations. In such conditions, the volume of corneocytes was
      increased but their stiffness was reduced. CONCLUSION: By analyzing the tape
      striped SC, we were able to measure the changes in the optical and physical
      properties of corneocytes in response to OCAs. Hydration of the SC layer by OCAs
      reduces light scattering from the corneocytes and would be helpful in
      moisturizing the skin and helping the skin look healthy.

PMID- 29377415
TI  - Molecular epidemiology of respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is a major cause of viral acute respiratory
      tract infections in young children. The virus is characterised by distinct
      seasonality that is dependent upon the latitude and its ability to cause
      reinfection. Respiratory syncytial virus demonstrates a complex molecular
      epidemiology pattern as multiple strains and/or genotypes cocirculate during a
      single epidemic. Previous studies have investigated the relationship between RSV
      genetic diversity, reinfection, and clinical features. Here, we review the
      evidence behind this relationship together with the impact that the advancement
      of whole genome sequencing will have upon our understanding and the need for
      reconsidering the classification of RSV genotypes.

PMID- 29377416
TI  - Oncologic outcomes of extended neck dissections in human papillomavirus-related
      oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: Oncologic outcomes of human papillomavirus (HPV)-related
      oropharyngeal squamous cell carcinoma (SCC) requiring resection of major muscular
      or neurovascular tissue during neck dissection for invasive nodal disease remain
      uncertain. METHODS: Patients with HPV-related oropharyngeal SCC requiring
      resection of major muscular or neurovascular tissue during their neck dissections
      were retrospectively identified. RESULTS: Seventy-two patients were included.
      Regional and distant recurrences occurred in 6% and 17% of patients. Advanced T
      classification, pathological node number of 5 or more, and omission of adjuvant
      therapy were associated with decreased disease-free survival (DFS). The addition
      of adjuvant chemotherapy was not associated with improved survival. CONCLUSION:
      Patients with invasive nodal disease from HPV-related oropharyngeal SCC can be
      managed with up-front surgery and adjuvant therapy, as indicated with good
      regional control. Although distant recurrence was the primary site of failure,
      adjuvant chemotherapy was not associated with improved outcomes. The T
      classification, node number, and adjuvant radiotherapy are independent prognostic
      factors in this patient population.

PMID- 29377417
TI  - Diversity of Cercomonad Species in the Phyllosphere and Rhizosphere of Different
      Plant Species with a Description of Neocercomonas epiphylla (Cercozoa, Rhizaria)
      a Leaf-Associated Protist.
AB  - Cercomonads are among the most abundant and diverse groups of heterotrophic
      flagellates in terrestrial systems and show an affinity to plants. However, we
      still lack basic knowledge of plant-associated protists. We isolated 75
      Cercomonadida strains from the phyllosphere and rhizosphere of plants from three
      functional groups: grasses (Poa sp.), legumes (Trifolium sp.) and forbs (Plantago
      sp.), representing 28 OTUs from the genera Cercomonas, Neocercomonas and
      Paracercomonas. The community composition differed clearly between phyllosphere
      and rhizosphere, but was not influenced by plant species identity. From these
      isolates we describe three novel cercomonad species including Neocercomonas
      epiphylla that was consistently and exclusively isolated from the phyllosphere.
      For each new species we provide a detailed morphological description as well as
      an 18S rDNA gene sequence as a distinct marker of species identity. Our data
      contribute to a better resolution of the systematics of cercomonads and their
      association with plants, by describing three novel species and adding gene
      sequences of 10 new cercomonad genotypes and of nine previously described
      species. In view of the functional importance of cercozoan communities in the
      phyllosphere and rhizosphere of plants, a more detailed understanding of their
      composition, function and predator-prey interactions are clearly required.

PMID- 29377418
TI  - Ventricular arrhythmias and cardiomyopathies: Is life always worth living?

PMID- 29377419
TI  - Assessment of left ventricular dyssynchrony by three-dimensional
      echocardiography: Prognostic value in patients undergoing cardiac
      resynchronization therapy.
AB  - BACKGROUND: Systolic dyssynchrony index (SDI) using three-dimensional
      echocardiography (3DE) was shown to be a reliable measure of left ventricular
      (LV) dyssynchrony. However, the prognostic value of SDI on long-term outcomes
      after cardiac resynchronization therapy (CRT) remains unknown. METHODS AND
      RESULTS: A total of 414 patients (mean age 67 +/- 10 years, 60% ischemic
      etiology) with 3DE evaluation before CRT implantation were included. SDI was
      evaluated as continuous value and in quartiles. The study endpoint was combined
      all-cause mortality, heart transplantation, and LV assist device implantation. At
      baseline, median SDI was 8.0% (IQR 5.6-11.3%). During a median follow-up of 45
      months (IQR 25-59 months), the endpoint was observed in 94 (23%) patients. SDI
      was independently associated with the endpoint together with ischemic etiology,
      diabetes, and renal function (HR 0.914, P = 0.003) after adjustment for age,
      atrial fibrillation, hemoglobin level, NYHA functional class, and posterolateral
      LV lead position. Patients from the 1st, 2nd, and 3rd SDI quartiles showed
      similar survival and superior as compared to the 4th quartile with the lowest SDI
      values (<=5.5%; chi2: 30.4, log-rank P < 0.001). From receiver operating
      characteristic curve analysis, the optimal SDI cut-off value associated with the
      endpoint was >6.8% (area under the curve 0.634). Finally, a subgroup analysis
      (293 patients) demonstrated that a more pronounced reduction in SDI immediately
      after CRT (resynchronization) was independently associated with superior survival
      (HR 0.461, P = 0.011) after adjustment for prognostic relevant parameters.
      CONCLUSION: SDI is independently associated with long-term prognosis after CRT
      and might therefore be important to optimize risk-stratification in these
      patients.

PMID- 29377420
TI  - Transformation of the gas-phase favored O-protomer of p-aminobenzoic acid to its
      unfavored N-protomer by ion activation in the presence of water vapor: An ion
      mobility mass spectrometry study.
AB  - An ion-mobility mass spectrometry study showed that the preferred O-protonated
      form of p-aminobenzoic in the gas phase can be converted to the thermodynamically
      less favored N-protomer by in-source collision-induced ion activation during the
      ion transfer process from the atmospheric region to the first vacuum region if
      the humidity is high in the ion source. Upon the addition of water vapor to the
      nitrogen gas used to promote the solid analyte to the gas phase under helium
      plasma ionization conditions, the intensity of the ion-mobility arrival-time peak
      for the N-protomer increased dramatically. Evidently, the ion-activation process
      in the first vacuum region is able to provide the energy required to surmount the
      barrier to isomerize the O-protomer to the more energetic N-protomer. The
      transfer of the proton attached to the carbonyl oxygen atom of the O-protomer to
      the amino group takes place by a water-bridge mechanism. Apparently, the
      postionization transformations that take place during the transmission of ions
      from the atmospheric-pressure ion source to the detector, via different physical
      compartments of low to high vacuum, play an eminent role in determining the
      population ratios eventually manifested at the detector.

PMID- 29377421
TI  - Corrigendum: Epitope Targeting of Tertiary Protein Structure Enables Target
      Guided Synthesis of a Potent In-Cell Inhibitor of Botulinum Neurotoxin.

PMID- 29377422
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 6/2018.

PMID- 29377423
TI  - Brown adipose tissue lipid metabolism in morbid obesity: Effect of bariatric
      surgery-induced weight loss.
AB  - OBJECTIVE: We aimed to investigate the effect of bariatric surgery on lipid
      metabolism in supraclavicular brown adipose tissue in morbidly obese women. We
      hypothesized that lipid metabolism improves after surgery-induced weight loss.
      MATERIALS AND METHODS: A total of 23 morbidly obese women (BMI, 42.1 +/- 4.2
      kg/m2 ; age, 43.8 +/- 9.8 years) were assessed before and 6 months after
      bariatric surgery and 15 age- and sex-matched controls (22.6 +/- 2.8 kg/m2 ) were
      assessed once. In the supraclavicular fat depot, fractional (FUR) and NEFA uptake
      rates were measured with 18 F-FTHA-PET. We assessed tissue morphology
      (triglyceride content) using computed tomography (CT)-radiodensity (in Hounsfield
      Units[HU]) and the proportion of fat with high density (sBAT [%]) in the entire
      supraclavicular fat depot. RESULTS: The supraclavicular fractional uptake rate
      was lower in obese women compared to controls (0.0055 +/- 0.0035 vs 0.0161 +/-
      0.0177 1/min, P = .001). Both FUR (to 0.0074 +/- 0.0035 1/min, P = .01) and NEFA
      uptake rates (to 0.50 +/- 0.50 MUmol/100 g/min, P = .001) increased after
      surgery. Compared to controls, obese women had lower CT-radiodensity (-101.2 +/-
      10.1 vs -82.5 +/- 5.8 HU, P < .001) and sBAT (43.4 +/- 8.4% vs 64.5 +/- 12.4%, P
      < .001). After surgery, CT-radiodensity increased (to -82.5 +/- 9.6 HU, P <
      .001), signifying decreased triglyceride content and sBAT improved (to 58.0 +/-
      10.7%, P < .001), indicating an increased proportion of brown fat. The change in
      tissue morphology, reflected as increase in CT-radiodensity and sBAT (%), was
      associated with a decrease in adiposity indices and an increase in whole-body
      insulin sensitivity. CONCLUSIONS: A decrease in triglyceride content, coupled
      with the increased proportion of brown adipose tissue in the supraclavicular fat
      depot, may play a role in the improvement of whole-body insulin sensitivity
      observed in morbidly obese women after surgery-induced weight loss.

PMID- 29377424
TI  - Toward High-Performance Vacuum-Deposited OLEDs: Sublimable Cationic Iridium(III)
      Complexes with Yellow and Orange Electroluminescence.
AB  - Great advances in the development of efficient luminescent materials are the
      driving force behind organic light-emitting diodes (OLEDs). Sublimable ionic
      transition-metal complexes (iTMCs) have emerged as a large family of new emissive
      dopants applied for vacuum-deposited OLEDs, while the achievement of excellent
      performance remains arduous. A series of novel sublimable cationic iridium(III)
      complexes have been designed and synthesized, containing an imidazole-type
      ancillary ligand and tetraphenylborate-type negative counter-ions with large
      steric hindrance and well-dispersed charges. The photophysical properties,
      electrochemical behaviors, and thermal stability are fully investigated and
      discussed, then demonstrated by theoretical calculations. Yellow- and orange
      emitting OLEDs thereof are fabricated by vacuum evaporation deposition, realizing
      a high external quantum efficiency of up to 11 %, maximum brightness over
      27.3*103  cd m-2 and low turn-on voltages below 2.4 V, among the best results of
      analogous phosphorescent OLEDs based on iTMCs. This work indicates the promising
      applications of sublimable iTMCs in state-of-the-art vacuum-deposited
      optoelectronic devices.

PMID- 29377426
TI  - Authors' reply re: Vaginal seeding or vaginal microbial transfer from the mother
      to the caesarean-born neonate: a commentary regarding clinical management.

PMID- 29377425
TI  - Identification of Tumor Initiating Cells with a Small-Molecule Fluorescent Probe
      by Using Vimentin as a Biomarker.
AB  - Tumor initiating cells (TICs) have been implicated in clinical relapse and
      metastasis of a variety of epithelial cancers, including lung cancer. While
      efforts toward the development of specific probes for TIC detection and targeting
      are ongoing, a universal TIC probe has yet to be developed. We report the first
      TIC-specific fluorescent chemical probe, TiY, with identification of the
      molecular target as vimentin, a marker for epithelial-to-mesenchymal transition
      (EMT). TiY selectively stains TICs over differentiated tumor cells or normal
      cells, and facilitates the visualization and enrichment of functionally active
      TICs from patient tumors. At high concentration, TiY also shows anti-TIC activity
      with low toxicity to non-TICs. With the unexplored target vimentin, TiY shows
      potential as a first universal probe for TIC detection in different cancers.

PMID- 29377427
TI  - Isoflavonoids from Brazilian red propolis down-regulate the expression of cancer
      related target proteins: A pharmacogenomic analysis.
AB  - Vestitol and neovestitol are bioactive isoflavonoids isolated from Brazilian red
      propolis, a unique Apis melifera type of propolis botanically originated from
      Dalbergia ecastophyllum. Although these molecules have relevant biological
      effects, including anticancer and immunomodulatory activities, their mechanism(s)
      of action and the affected pathways remain largely unknown. Here, we carried out
      a pharmacogenomic analysis to investigate the effects of vestitol and neovestitol
      on the whole-genome expression in human tumor cells, particularly cancer-related
      target proteins. HeLa cells were exposed to the compounds at IC20 and genomic
      information of treated cells was analyzed using the Illumina transcriptome system
      and GeneGo MetaCore software. Our results showed that vestitol (IC20  = 214.7
      MUM) reduced the expression of genes enrolled with the alpha tubulin (fold -3.7),
      tubulin in microtubules (fold -3.7), and histone h3 (fold = -3.03), and that
      treatment with neovestitol (IC20  = 102.91 MUM) downregulated prostaglandin E
      synthase gene (fold = -3.12), which are considered ideal targets for anticancer
      therapy. These data open avenues for the study of vestitol and neovestitol as
      potential promising candidates for anticancer therapy. Toxicological, non
      clinical, and clinical validation of the findings presented herein is needed.

PMID- 29377428
TI  - Improved Performance of Printable Perovskite Solar Cells with Bifunctional
      Conjugated Organic Molecule.
AB  - A bifunctional conjugated organic molecule 4-(aminomethyl) benzoic acid
      hydroiodide (AB) is designed and employed as an organic cation in organic
      inorganic halide perovskite materials. Compared with the monofunctional cation
      benzylamine hydroiodide (BA) and the nonconjugated bifunctional organic molecule
      5-ammonium valeric acid, devices based on AB-MAPbI3 show a good stability and a
      superior power conversion efficiency of 15.6% with a short-circuit current of
      23.4 mA cm-2 , an open-circuit voltage of 0.94 V, and a fill factor of 0.71. The
      bifunctional conjugated cation not only benefits the growth of perovskite
      crystals in the mesoporous network, but also facilitates the charge transport.
      This investigation helps explore new approaches to rational design of novel
      organic cations for perovskite materials.

PMID- 29377429
TI  - Obesity class does not further stratify outcome in overweight and obese pediatric
      patients after heart transplantation.
AB  - The effect of obesity stratification on pediatric heart transplant outcomes is
      unknown. The UNOS database was queried for patients >=2-<18 years listed for
      heart transplant and stratified by BMI: normal (BMI>5%-<=85 percentile),
      overweight (BMI=86%-95 percentile), class 1 (BMI=100%-120% of 95 percentile),
      class 2 (BMI=121%-140% of 95 percentile), and class 3 obesity (BMI>140% of 95
      percentile). A total of 5056 individuals were listed for transplant, with 71%
      normal, 13% overweight, 10% class 1, 4% class 2, and 2% class 3 obesity. Waitlist
      survival was not different between groups. Post-transplant survival was decreased
      in overweight and combined obese groups vs normal, with no further difference
      between overweight and obese classes. Overweight and obese patients had higher
      listing status and were more likely to have ventilator, inotrope, and mechanical
      circulatory support at listing. After transplant, there was an association of
      overweight-obese patients with diabetes and rejection requiring hospitalization.
      Stricter definition of normal weight reveals overweight-obese status was an
      independent risk factor for poorer post-transplant survival, without further
      effect by stratification of weight class. However, because there is no difference
      in waitlist survival, this study does not allow the selection of absolute weight
      based criteria regarding transplant listing and suggests the need to look further
      for modifiable risk factors post-transplant.

PMID- 29377430
TI  - Preclinical characterization of three transient receptor potential vanilloid
      receptor 1 antagonists for early use in human intradermal microdose analgesic
      studies.
AB  - BACKGROUND: The transient receptor potential vanilloid receptor 1 (TRPV1) is a
      nonselective cation channel involved in the mediation of peripheral pain to the
      central nervous system. As such, the TRPV1 is an accessible molecular target that
      lends itself well to the understanding of nociceptive signalling. This study
      encompasses preclinical investigations of three molecules with the prospect to
      establish them as suitable analgesic model compounds in human intradermal pain
      relief studies. METHODS: The inhibitory effectiveness was evaluated by means of
      in vitro assays, TRPV1 expressing Chinese hamster ovary cells (CHO-K1) and rat
      dorsal root ganglion cultures in fluorescent imaging plate reader and whole cell
      patch clamp systems, as well as in vivo by capsaicin-evoked pain-related
      behavioural response studies in rat. Secondary pharmacology, pharmacokinetics and
      preclinical safety were also assessed. RESULTS: In vitro, all three compounds
      were effective at inhibiting capsaicin-activated TRPV1. The concentration
      producing 50% inhibition (IC50 ) determined was in the range of 3-32 nmol/L and
      10-501 nmol/L using CHO-K1 and dorsal root ganglion cultures, respectively. In
      vivo, all compounds showed dose-dependent reduction in capsaicin-evoked pain
      related behavioural responses in rat. None of the three compounds displayed any
      significant activity on any of the secondary targets tested. The compounds were
      also shown to be safe from a toxicological, drug metabolism and pharmacokinetic
      perspective, for usage in microgram doses in the human skin. CONCLUSION: The
      investigated model compounds displayed ideal compound characteristics as
      pharmacological and translational tools to address efficacy on the human native
      TRPV1 target in human skin in situ. SIGNIFICANCE: This work details the
      pharmaceutical work-up of three TRPV1-active investigational compounds, to obtain
      regulatory approval, for subsequent use in humans. This fast and cost-effective
      preclinical development path may impact research beyond the pain management area,
      as it allows human target engagement information gathering early in drug
      development.

PMID- 29377431
TI  - Strategies for Improving the Performance of Sensors Based on Organic Field-Effect
      Transistors.
AB  - Organic semiconductors (OSCs) have been extensively studied as sensing channel
      materials in field-effect transistors due to their unique charge transport
      properties. Stimulation caused by its environmental conditions can readily change
      the charge-carrier density and mobility of OSCs. Organic field-effect transistors
      (OFETs) can act as both signal transducers and signal amplifiers, which greatly
      simplifies the device structure. Over the past decades, various sensors based on
      OFETs have been developed, including physical sensors, chemical sensors,
      biosensors, and integrated sensor arrays with advanced functionalities. However,
      the performance of OFET-based sensors still needs to be improved to meet the
      requirements from various practical applications, such as high sensitivity, high
      selectivity, and rapid response speed. Tailoring molecular structures and
      micro/nanofilm structures of OSCs is a vital strategy for achieving better
      sensing performance. Modification of the dielectric layer and the
      semiconductor/dielectric interface is another approach for improving the sensor
      performance. Moreover, advanced sensory functionalities have been achieved by
      developing integrated device arrays. Here, a brief review of strategies used for
      improving the performance of OFET sensors is presented, which is expected to
      inspire and provide guidance for the design of future OFET sensors for various
      specific and practical applications.

PMID- 29377432
TI  - Accessing Tetravalent Transition-Metal Nitridophosphates through High-Pressure
      Metathesis.
AB  - Advancing the attainable composition space of a compound class can lead to
      fascinating materials. The first tetravalent metal nitridophosphate, namely Hf9-x
      P24 N52-4x O4x (x~1.84), was prepared by high-pressure metathesis. The Group 4
      nitridophosphates are now an accessible class of compounds. The high-pressure
      metathesis reaction using a multianvil setup yielded single crystals that were
      suitable for structure analysis. Magnetic properties of the compound indicate Hf
      in oxidation state +IV. Optical measurements show a band gap in the UV region.
      The presented route unlocks the new class of Group 4 nitridophosphates by
      significantly improving the understanding of this nitride chemistry. Hf9-x P24
      N52-4x O4x (x~1.84) is a model system and its preparation is the first step
      towards a systematic exploration of the transition-metal nitridophosphates.

PMID- 29377433
TI  - Our digital world: Are monthly issues anachronistic?

PMID- 29377434
TI  - A herbicide structure-activity analysis of the antimalarial lead compound
      MMV007978 against Arabidopsis thaliana.
AB  - BACKGROUND: To fight herbicide-resistant weeds, new herbicides are needed;
      particularly ones with new modes of action. Building on the revelation that many
      antimalarial drugs are herbicidal, here we focus on the Medicines for Malaria
      Venture antimalarial lead compound MMV007978 that has herbicidal activity against
      the model plant Arabidopsis thaliana. RESULTS: Twenty-two variations of the lead
      compound thiophenyl motif revealed that change was tolerated provided ring size
      and charge were retained. MMV007978 was active against select monocot and dicot
      weeds, and physiological profiling indicated that its mode of action is related
      to germination and cell division. Of interest is the fact that the compound has a
      profile that is currently not found among known herbicides. CONCLUSION: We
      demonstrate that the antimalarial compound MMV007978 is also herbicidal and that
      exploiting lead compounds that are often understudied could lead to the
      identification of interesting herbicidal scaffolds. Further structural
      investigation of MMV007978 could provide improved herbicidal chemistries with a
      potential new mode of action. (c) 2018 Society of Chemical Industry.

PMID- 29377435
TI  - Breakdown in the temporal and spatial organization of spontaneous brain activity
      during general anesthesia.
AB  - Which temporal features that can characterize different brain states (i.e.,
      consciousness or unconsciousness) is a fundamental question in the neuroscience
      of consciousness. Using resting-state functional magnetic resonance imaging (rs
      fMRI), we investigated the spatial patterns of two temporal features: the long
      range temporal correlations (LRTCs), measured by power-law exponent (PLE), and
      temporal variability, measured by standard deviation (SD) during wakefulness and
      anesthetic-induced unconsciousness. We found that both PLE and SD showed global
      reductions across the whole brain during anesthetic state comparing to
      wakefulness. Importantly, the relationship between PLE and SD was altered in
      anesthetic state, in terms of a spatial "decoupling." This decoupling was mainly
      driven by a spatial pattern alteration of the PLE, rather than the SD, in the
      anesthetic state. Our results suggest differential physiological grounds of PLE
      and SD and highlight the functional importance of the topographical organization
      of LRTCs in maintaining an optimal spatiotemporal configuration of the neural
      dynamics during normal level of consciousness. The central role of the spatial
      distribution of LRTCs, reflecting temporo-spatial nestedness, may support the
      recently introduced temporo-spatial theory of consciousness (TTC).

PMID- 29377436
TI  - Hepatitis E virus seroprevalence, seroincidence and seroreversion in the German
      adult population.
AB  - A steep rise in Hepatitis E diagnoses is currently being observed in Germany and
      other European countries. The objective of this study was (i) to assess whether
      this trend mirrors an increase in infection pressure or is caused by increased
      attention and testing and (ii) estimate individual and population-based Hepatitis
      E Virus (HEV) seroconversion and seroreversion rates for Germany. We measured
      anti-HEV IgG prevalence in 10 407 adults participating in two linked, population
      representative serosurveys (total n = 12 971) conducted in 1998 and 2010. In this
      period, we found a moderate but statistically significant decline of overall anti
      HEV IgG prevalence from 18.6% to 15.3%. At both time points, seroprevalence
      increased with age and peaked in persons born between 1935 and 1959 suggesting a
      past period of increased infection pressure. Paired samples of individuals
      participating in 1998 and 2010 (n = 2564) revealed respective seroconversion and
      seroreversion rates of 6.2% and 22.6% among seronegative and seropositive
      individuals during 12 years, or 5.2 and 2.9 per 1000 inhabitants per year. This
      corresponds to a total of 417 242 [95%CI: 344 363-495 971] new seroconversions
      per year in the German population. While anti-HEV seroprevalence has decreased in
      the last decade, infection pressure and seroincidence remains high in Germany.
      Continuously rising numbers of Hepatitis E diagnoses in Europe are likely due to
      an increased awareness of clinicians and indicate that still there is a gap
      between incident and diagnosed cases. Studies on the true burden of the disease,
      specific risk factors and sources of autochthonous infections as well as targeted
      prevention measures are urgently needed.

PMID- 29377437
TI  - Steatosis affects the sensitivity but not the specificity of non-invasive
      fibrosis tests in non-alcoholic fatty liver disease - implications for screening
      strategies.

PMID- 29377438
TI  - Author response to LIVint-17-01304 "The consideration of heart rate complexity as
      a co-morbidity factor for liver transplantation selection procedures".

PMID- 29377439
TI  - Oral oxycodone/naloxone for pain control in cirrhosis: Start slow, go slow.

PMID- 29377440
TI  - Clinical relevance of integrin alpha 4 in gastrointestinal stromal tumours.
AB  - The molecular mechanisms for the dissemination and metastasis of gastrointestinal
      stromal tumours (GIST) are incompletely understood. The purpose of the study was
      to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in
      GIST. GIST transcriptomes were first compared with transcriptomes of other types
      of cancer and histologically normal gastrointestinal tract tissue in the
      MediSapiens in silico database. ITGA4 was identified as an unusually highly
      expressed gene in GIST. Therefore, the effects of ITGA4 knock-down and selective
      integrin alpha 4 beta 1 (VLA-4) inhibitors on tumour cell proliferation and
      invasion were investigated in three GIST cell lines. In addition, the prognostic
      role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST
      patients with immunohistochemistry. Inhibition of ITGA4-related signalling
      decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein
      was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was
      significantly associated with distant metastases during the course of the disease
      and several adverse prognostic features. Patients whose GIST expressed strongly
      ITGA4 had unfavourable GIST-specific survival and overall survival compared to
      patients with low or no ITGA4 expression. Taken together, ITGA4 is an important
      integrin in the molecular pathogenesis of GIST and may influence their clinical
      behaviour.

PMID- 29377441
TI  - Glycosyl-Substituted Dicarboxylates as Detergents for the Extraction,
      Overstabilization, and Crystallization of Membrane Proteins.
AB  - To tackle the problems associated with membrane protein (MP) instability in
      detergent solutions, we designed a series of glycosyl-substituted dicarboxylate
      detergents (DCODs) in which we optimized the polar head to clamp the membrane
      domain by including, on one side, two carboxyl groups that form salt bridges with
      basic residues abundant at the membrane-cytoplasm interface of MPs and, on the
      other side, a sugar to form hydrogen bonds. Upon extraction, the DCODs 8 b, 8 c,
      and 9 b preserved the ATPase function of BmrA, an ATP-binding cassette pump, much
      more efficiently than reference or recently designed detergents. The DCODs 8 a, 8
      b, 8 f, 9 a, and 9 b induced thermal shifts of 20 to 29  degrees C for BmrA and
      of 13 to 21  degrees C for the native version of the G-protein-coupled adenosine
      receptor A2A R. Compounds 8 f and 8 g improved the diffraction resolution of BmrA
      crystals from 6 to 4 A. DCODs are therefore considered to be promising and
      powerful tools for the structural biology of MPs.

PMID- 29377442
TI  - Mechanisms of Dorsal Root Ganglion Stimulation in Pain Suppression: A
      Computational Modeling Analysis.
AB  - OBJECTIVE: The mechanisms of dorsal root ganglion (DRG) stimulation for chronic
      pain remain unclear. The objective of this work was to explore the
      neurophysiological effects of DRG stimulation using computational modeling.
      METHODS: Electrical fields produced during DRG stimulation were calculated with
      finite element models, and were coupled to a validated biophysical model of a C
      type primary sensory neuron. Intrinsic neuronal activity was introduced as a 4 Hz
      afferent signal or somatic ectopic firing. The transmembrane potential was
      measured along the neuron to determine the effect of stimulation on intrinsic
      activity across stimulation parameters, cell location/orientation, and membrane
      properties. RESULTS: The model was validated by showing close correspondence in
      action potential (AP) characteristics and firing patterns when compared to
      experimental measurements. Subsequently, the model output demonstrated that T
      junction filtering was amplified with DRG stimulation, thereby blocking afferent
      signaling, with cathodic stimulation at amplitudes of 2.8-5.5 * stimulation
      threshold and frequencies above 2 Hz. This amplified filtering was dependent on
      the presence of calcium and calcium-dependent small-conductance potassium
      channels, which produced a hyperpolarization offset in the soma, stem, and T
      junction with repeated somatic APs during stimulation. Additionally, DRG
      stimulation suppressed somatic ectopic activity by hyperpolarizing the soma with
      cathodic or anodic stimulation at amplitudes of 3-11 * threshold and frequencies
      above 2 Hz. These effects were dependent on the stem axon being relatively close
      to and oriented toward a stimulating contact. CONCLUSIONS: These results align
      with the working hypotheses on the mechanisms of DRG stimulation, and indicate
      the importance of stimulation amplitude, polarity, and cell location/orientation
      on neuronal responses.

PMID- 29377443
TI  - Salvinorin A ameliorates cerebral vasospasm through activation of endothelial
      nitric oxide synthase in a rat model of subarachnoid hemorrhage.
AB  - OBJECTIVE: This study aimed to demonstrate the potential of salvinorin A (SA) for
      cerebral vasospasm after subarachnoid hemorrhage (SAH) and investigate mechanisms
      of therapeutic effect using rat SAH model. METHODS: Salvinorin A was injected
      intraperitoneally, and the neurobehavioral changes were observed at 12 hours, 24
      hours, 48 hours, and 72 hours after SAH. Basilar artery was observed by magnetic
      resonance imaging (MRI). The inner diameter and thickness of basilar artery were
      measured. The morphological changes and the apoptosis in CA1 area of hippocampus
      were detected. Endothelin-1 (ET-1) and nitric oxide (NO) levels were detected by
      ELISA kit. The protein expression of endothelial NO synthase (eNOS) and aquaporin
      4 (AQP-4) was determined by Western blot for potential mechanism exploration.
      RESULTS: Salvinorin A administration could relieve neurological deficits,
      decrease the neuronal apoptosis, and alleviate the morphological changes in CA1
      area of hippocampus. SA alleviated CVS by increasing diameter and decreasing
      thickness of basilar artery, and such changes were accompanied by the decreased
      concentration of ET-1 and increased level of NO. Meanwhile, SA increased the
      expression of eNOS and decreased the expression of AQP-4 protein in the basilar
      artery and hippocampus. CONCLUSIONS: Salvinorin A attenuated CVS and alleviated
      brain injury after SAH via increasing expression of eNOS and NO content, and
      decreasing ET-1 concentration and AQP-4 protein expression.

PMID- 29377444
TI  - An Induced Pluripotent Stem Cell Patient Specific Model of Complement Factor H
      (Y402H) Polymorphism Displays Characteristic Features of Age-Related Macular
      Degeneration and Indicates a Beneficial Role for UV Light Exposure.

PMID- 29377446
TI  - Association between periodontitis and chronic kidney disease: Systematic review
      and meta-analysis.
AB  - A systematic review and meta-analysis were conducted to evaluate the association
      between periodontitis (PD) and chronic kidney disease (CKD) and to explore the
      potential influence of periodontal treatment in patients with CKD. Databases
      (PubMed, Web of Science, Science direct, Cochrane Database) were screened for
      relevant articles, focusing on the periodontal status of patients with CKD,
      published until December 2017. Five hundred and fifty-three articles were
      identified, and 37 fulfilled the inclusion criteria and were considered in this
      systematic review. Seventeen articles were included in the meta-analysis and 7 in
      the review focusing on the impact of periodontal treatment. Most of the
      identified studies indicated an increased incidence of PD in patients with CKD.
      Meta-analysis showed an association between CKD and PD, and strength of this
      association was increased when severe PD was considered (OR = 2.39 (1.70-3.36)).
      The association could be observed even after adjustment for major CKD risk
      factors or use of precise diagnosis criteria (OR = 2.26 for severe PD (1.69
      3.01)). Analysis of cohort studies indicated an incident rate ratio (IRR) of
      1.73. Periodontitis is associated with CKD after multivariable adjustment.
      Further studies are necessary to determine whether prevention or treatment of PD
      can reduce the incidence and/or severity of CKD.

PMID- 29377445
TI  - Grapevine VpPR10.1 functions in resistance to Plasmopara viticola through
      triggering a cell death-like defence response by interacting with VpVDAC3.
AB  - As one of the most serious diseases in grape, downy mildew caused by Plasmopara
      viticola is a worldwide grape disease. Much effort has been focused on improving
      susceptible grapevine resistance, and wild resistant grapevine species are
      important for germplasm improvement of commercial cultivars. Using yeast two
      hybrid screen followed by a series of immunoprecipitation experiments, we
      identified voltage-dependent anion channel 3 (VDAC3) protein from Vitis piasezkii
      'Liuba-8' as an interacting partner of VpPR10.1 cloned from Vitis
      pseudoreticulata 'Baihe-35-1', which is an important germplasm for its resistance
      to a range of pathogens. Co-expression of VpPR10.1/VpVDAC3 induced cell death in
      Nicotiana benthamiana, which accompanied by ROS accumulation. VpPR10.1 transgenic
      grapevine line showed resistance to P. viticola. We conclude that the
      VpPR10.1/VpVDAC3 complex is responsible for cell death-mediated defence response
      to P. viticola in grapevine.

PMID- 29377447
TI  - Baseline susceptibility of Mediterranean strains of Trialeurodes vaporariorum
      (Westwood) to cyantraniliprole.
AB  - BACKGROUND: Cyantraniliprole is a novel anthranilic diamide insecticide that acts
      on a broad spectrum of insect pests, exclusively by activating their ryanodine
      receptors. Cyantraniliprole is very effective against whitefly and it presents a
      favorable ecotoxicological profile. In this study, the baseline susceptibility to
      cyantraniliprole of Trialeurodes vaporariorum populations from the Mediterranean
      area was established in nymphal systemic uptake bioassays. RESULTS: The bioassay
      data showed that the susceptibility to cyantraniliprole varied among the strains
      collected across the Mediterranean basin. The 50% lethal concentration (LC50 )
      range of cyantraniliprole for 16 field populations was from 0.017 to 0.194 mg L-1
      , a 11.4-fold natural variability between the least and most sensitive
      populations. These LC50 values are similar to those reported in a previous study
      of the use of cyantraniliprol against another species of whitefly, Bemisia tabaci
      [LC50  = 0.048 (0.034-0.063) mg L-1 ]. CONCLUSION: The current study confirmed
      the effectiveness of cyantraniliprole against T. vaporarioum strains, adding to
      the evidence that cyantraniliprole is a promising tool for use in integrated pest
      management programs. Future shifts in the susceptibility of whitefly field
      populations to cyantraniliprole may be documented according to the baseline
      susceptibility range of the populations tested in this research. (c) 2018 Society
      of Chemical Industry.

PMID- 29377448
TI  - Incidence of intracardiac thrombus formation prior to electrical cardioversion in
      respect to the mode of oral anticoagulation.
AB  - AIMS: To evaluate the incidence of newly diagnosed intracardiac thrombi (ICT) in
      respect to the mode of OAC in patients undergoing cardioversion (CV). METHODS AND
      RESULTS: We prospectively assessed transesophageal echocardiography (TEE) and OAC
      therapy prior to CV in AF patients with >=48-hour duration scheduled for CV. A
      total of 60 first-time ICT (4.7%) were diagnosed in 1,286 TEE, with highest rate
      in patients without OAC (9.6% vs. OAC 4.1%, P  =  0.009) and an apparently lower
      rate in nonvitamin K antagonist anticoagulants (NOAC) therapy compared to vitamin
      K antagonist (VKA) (2.5% vs. 5.3%, P  =  0.02). VKA therapy control 4 weeks prior
      to CV was overall average (time in therapeutic range 60%) and patients showed
      more frequently clinical characteristics and TEE parameters associated with risk
      for ICT. Even among patients with effective OAC therapy (uninterrupted NOAC and
      VKA therapy with international normalized ratio (INR) >=2.0 for 3 weeks), ICT
      occurred in 2.7%, but with no difference between both groups (P  =  0.22). There
      was no difference between different types of NOAC. Independent predictors for ICT
      were history of embolism, hypertension, BMI, absence of OAC, renal function,
      reduced atrial appendage flow, and presence of spontaneous echo contrast.
      CONCLUSION: NOAC therapy seems favorable in the overall prevention of ICT,
      although this is likely to be caused by suboptimal VKA therapy control and
      differences in the overall health status between VKA and NOAC patients. ICT
      occurred even with effective OAC therapy suggesting individual TEE-guided
      cardioversion in patients at risk.

PMID- 29377449
TI  - In the grass species Brachypodium distachyon, the production of mixed-linkage
      (1,3;1,4)-beta-glucan (MLG) occurs in the Golgi apparatus.
AB  - Mixed-linkage (1,3;1,4)-beta-glucan (MLG) is a glucose polymer with beneficial
      effects on human health and high potential for the agricultural industry. MLG is
      present predominantly in the cell wall of grasses and is synthesized by cellulose
      synthase-like F or H families of proteins, with CSLF6 being the best
      characterized MLG synthase. Although the function of this enzyme in MLG
      production has been established, the site of MLG synthesis in the cell is
      debated. It has been proposed that MLG is synthesized at the plasma membrane, as
      occurs for cellulose and callose; in contrast, it has also been proposed that MLG
      is synthesized in the Golgi apparatus, as occurs for other matrix polysaccharides
      of the cell wall. Testing these conflicting possibilities is fundamentally
      important in the general understanding of the biosynthesis of the plant cell
      wall. Using immuno-localization analyses with MLG-specific antibody in
      Brachypodium and in barley, we found MLG present in the Golgi, in post-Golgi
      structures and in the cell wall. Accordingly, analyses of a functional
      fluorescent protein fusion of CSLF6 stably expressed in Brachypodium demonstrated
      that the enzyme is localized in the Golgi. We also established that
      overproduction of MLG causes developmental and growth defects in Brachypodium as
      also occur in barley. Our results indicated that MLG production occurs in the
      Golgi similarly to other cell wall matrix polysaccharides, and supports the
      broadly applicable model in grasses that tight mechanisms control optimal MLG
      accumulation in the cell wall during development and growth. This work addresses
      the fundamental question of where mixed linkage (1,3;1,4)-beta-glucan (MLG) is
      synthesized in plant cells. By analyzing the subcellular localization of MLG and
      MLG synthase in an endogenous system, we demonstrated that MLG synthesis occurs
      at the Golgi in Brachypodium and barley. A growth inhibition due to overproduced
      MLG in Brachypodium supports the general applicability of the model that a tight
      control of the cell wall polysaccharides accumulation is needed to maintain
      growth homeostasis during development.

PMID- 29377450
TI  - The absence of serum IgE antibodies indicates non-type 2 disease in young
      asthmatics.
AB  - BACKGROUND: Atopic asthma is associated with elevated type-2 biomarkers such as
      fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count.
      However, increased type 2 markers have also been reported in traditionally
      defined non-atopic asthma. OBJECTIVE: To determine a clinically useful level of
      IgE sensitization for ruling out type 2 asthma. METHODS: Asthmatics (N = 408; age
      10-35 years) were analysed using the multi-allergen tests Phadiatop and fx5
      (ImmunoCAP). Subjects were grouped based on IgE-antibody concentrations: >=0.35
      kUA /L for at least one test (n = 326) or <0.35 kUA /L for both tests (n = 82).
      Tauhe latter group was subsequently divided into 2 groups: IgE 0.10-0.34 kUA /L
      (n = 34) and IgE < 0.10 kUA /L (n = 48). The relationships between type 2
      biomarkers, and inadequate asthma control (ACT < 20), reduced lung function (FEV1
      < 80%), recent asthma attacks and airway hyperresponsiveness (AHR) to
      methacholine were determined. RESULTS: In univariate analyses, at least one type
      2 marker related to each asthma outcome in subjects with IgE >=0.35 kUA /L. In
      subjects with IgE 0.10-0.34 kUA /L, elevated FeNO related to reduced lung
      function (P = .008) and B-Eos to AHR (P = .03). No associations were found in
      subjects with IgE < 0.10 kUA /L. In multivariate analysis, a relationship between
      FeNO and reduced lung function remained in subjects with IgE < 0.35 kUA /L (P =
      .03). CONCLUSION AND CLINICAL RELEVANCE: Clinically relevant elevation of type 2
      biomarkers was seen in young asthmatics with IgE antibodies <0.35 kUA /L, but not
      those with IgE < 0.10 kUA /L. It seems possible to define non-type 2 asthma
      through sensitive IgE-antibody measurement.

PMID- 29377451
TI  - Alternative splicing associated with phenotypic plasticity in the bumble bee
      Bombus terrestris.
AB  - Phenotypic plasticity is when one genome can produce more than one phenotype. The
      caste system found in many social insects is an important example of plasticity.
      Several studies have examined gene expression in social insect developmental and
      caste differences. Changes in gene expression, however, are not the only source
      of phenotypic plasticity. Here, we investigate the role of alternative splicing
      in the buff-tailed bumble bee Bombus terrestris. We found that 5,458 genes in B.
      terrestris (40%) express more than one isoform. Larvae have the lowest level of
      splicing events, followed by adults and then pupae. We found that when an isoform
      is expressed in a given caste in the larval stage, it tends to be expressed in
      all castes at the larval stage. The same is true at the pupal stage. However, we
      see more complicated interactions between the adult castes with reproductive
      females showing different isoform expression compared to nonreproductive females
      and male adults showing the most distinct patterns. We found 455 isoform
      switching genes, that is genes, where one developmental stage, sex or caste uses
      a specific isoform and another type uses a different isoform. Among genes
      displaying isoform switching are some involved in the ecdysteriod pathway, an
      important system in insect behaviour.

PMID- 29377452
TI  - Papilla-Crown Height Dimensions around Zirconium Dioxide Implants in the Esthetic
      Area: A 3-Year Follow-Up Study.
AB  - PURPOSE: Soft tissue interactions with ceramic dental implants have previously
      been shown to have favorable esthetic outcomes. This study aimed to evaluate the
      papilla-crown proportion around zirconia implants in a 3-year follow-up study and
      the correlation between the gingival biotype and changes in papillary height.
      MATERIALS AND METHODS: This was a prospective study of 39 patients with 40 single
      gap implants (Straumann PURE Ceramic ZLA Implant). The papilla-crown proportion
      was assessed after 3 months, 1 year, and 3 years. In addition, correlations
      between the peri-implant biotypes and changes in papillary heights were
      evaluated. RESULTS: The papilla-crown proportion improved from 35.5% after 3
      months to 41.7% after 3 years. The gingival biotype was correlated very weakly to
      papilla height alterations. Significant papillary fill was observed in the
      interdental space between 3 months and 3 years (p < 0.001). CONCLUSIONS: An ideal
      papilla-crown proportion of 40% around single implants was observed after 3
      years. A thin or thick gingival biotype showed a very weak correlation with soft
      tissue alterations.

PMID- 29377453
TI  - Reciprocal associations of pain and post-traumatic stress symptoms after whiplash
      injury: A longitudinal, cross-lagged study.
AB  - BACKGROUND: The objectives of the current study were to investigate (1) the
      longitudinal, reciprocal associations between pain and post-traumatic stress
      symptoms as proposed by the mutual maintenance model, and (2)  to assess the
      predictive value of the three clusters of post-traumatic stress, where the model
      revealed that post-traumatic stress symptoms maintained pain in a consecutive
      cohort of whiplash-injured. METHODS: Participants (n = 253; 66.4% women) were
      people with WAD grades I-III following motor vehicle crashes in Australia. Pain
      and post-traumatic stress symptoms were assessed by questionnaires over the
      course of a year (at baseline (<4 weeks), 3, 6 and 12 months post-injury). The
      objectives were tested using auto-regressive cross-lagged modelling and two
      additional structural equation models. RESULTS: The analyses revealed that post
      traumatic stress symptoms at baseline predicted an increase in pain between
      baseline and 3 months and that post-traumatic stress symptoms at 6 months
      predicted an increase in pain between 6 and 12 months, beyond the stability of
      pain over time. Furthermore, hyperarousal at baseline significantly predicted
      pain at 3 months and hyperarousal at 6 months significantly predicted pain at 12
      months with 16 and 23% explained variance, respectively. [Correction added on 2
      March 2018 after first online publication: the explained variance for
      hyperarousal symptoms at 6 months was previously given incorrectly and has been
      corrected to 23% in this version.] CONCLUSIONS: The results point to a temporal
      main effect of post-traumatic stress symptoms on pain over and above the
      stability of pain itself within the first 3 months post-injury and again in the
      chronic phase from 6 to 12 months with hyperarousal symptoms driving these
      effects. From 3 to 6 months, there was a slip in the maintenance patterns with no
      cross-lagged effects. SIGNIFICANCE: Investigating mutual maintenance of pain and
      PTSS in whiplash, the present study found evidence suggesting a maintaining
      effect of PTSS on pain within the first 3 months post-injury and from 6 to 12
      months driven by hyperarousal, highlighting the importance of addressing PTSS.

PMID- 29377454
TI  - Mono-allyloxylated Cucurbit[7]uril Acts as an Unconventional Amphiphile To Form
      Light-Responsive Vesicles.
AB  - Serendipitously, mono-allyloxylated cucurbit[7]uril (AO1 CB[7]) was discovered to
      act as an unconventional amphiphile which self-assembles into light-responsive
      vesicles (AO1 CB[7]VC) in water. Although the mono-allyloxy group, directly
      tethered on the periphery of CB[7], is much shorter (C4) than the hydrophobic
      tails of conventional amphiphiles, it played an important role in vesicle
      formation. Light-activated transformation of the allyloxy group by conjugation
      with glutathione was exploited as a remote tool to disrupt the vesicle. The
      vesicle showed on-demand release of cargo upon irradiation by a laser, after they
      were internalized into cancer cells. This result demonstrated the potential of
      AO1 CB[7]VC as a new type of light-responsive intracellular delivery vehicle for
      the release of therapeutic cargo, within cells, on demand.

PMID- 29377455
TI  - LysoTracker and MitoTracker Red are transport substrates of P-glycoprotein:
      implications for anticancer drug design evading multidrug resistance.
AB  - LysoTracker and MitoTracker Red are fluorescent probes widely used for viable
      cell staining of lysosomes and mitochondria, respectively. They are utilized to
      study organelle localization and their resident proteins, assess organelle
      functionality and quantification of organelle numbers. The ATP-driven efflux
      transporter P-glycoprotein (P-gp) is expressed in normal and malignant tissues
      and extrudes structurally distinct endogenous and exogenous cytotoxic compounds.
      Thus, once aromatic hydrophobic compounds such as the above-mentioned fluorescent
      probes are recognized as transport substrates, efflux pumps including P-gp may
      abolish their ability to reach their cellular target organelles. Herein, we show
      that LysoTracker and MitoTracker Red are expelled from P-gp-overexpressing cancer
      cells, thus hindering their ability to fluorescently mark target organelles. We
      further demonstrate that tariquidar, a potent P-gp transport inhibitor, restores
      LysoTracker and MitoTracker Red cell entry. We conclude that LysoTracker and
      MitoTracker Red are P-gp transport substrates, and therefore, P-gp expression
      must be taken into consideration prior to cellular applications using these
      probes. Importantly, as MitoTracker was a superior P-gp substrate than
      LysoTracker Red, we discuss the implications for the future design of
      chemotherapeutics evading cancer multidrug resistance. Furthermore, restoration
      of MitoTracker Red fluorescence in P-gp-overexpressing cells may facilitate the
      identification of potent P-gp transport inhibitors (i.e. chemosensitizers).

PMID- 29377456
TI  - DNA Origami Directed Assembly of Gold Bowtie Nanoantennas for Single-Molecule
      Surface-Enhanced Raman Scattering.
AB  - Metallic bowtie nanoarchitectures can produce dramatic electric field
      enhancement, which is advantageous in single-molecule analysis and optical
      information processing. Plasmonic bowtie nanostructures were successfully
      constructed using a DNA origami-based bottom-up assembly strategy, which enables
      precise control over the geometrical configuration of the bowtie with an
      approximate 5 nm gap. A single Raman probe was accurately positioned at the gap
      of the bowtie. Single-molecule surface-enhanced Raman scattering (SM-SERS) of
      individual nanostructures, including ones containing an alkyne group, was
      observed. The design achieved repeatable local field enhancement of several
      orders of magnitude. This method opens the door on a novel strategy for the
      fabrication of metal bowtie structures and SM-SERS, which can be utilized in the
      design of highly-sensitive photonic devices.

PMID- 29377457
TI  - Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by
      Cyclodipeptide Synthases.
AB  - The manipulation of natural product biosynthetic pathways is a powerful means of
      expanding the chemical diversity of bioactive molecules. 2,5-diketopiperazines
      (2,5-DKPs) have been widely developed by medicinal chemists, but their biological
      production is yet to be exploited. We introduce an in vivo method for
      incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using
      cyclodipeptide synthases (CDPSs), the enzymes responsible for scaffold assembly
      in many 2,5-DKP biosynthetic pathways. CDPSs use aminoacyl-tRNAs as substrates.
      We exploited the natural ability of aminoacyl-tRNA synthetases to load ncAAs onto
      tRNAs. We found 26 ncAAs to be usable as substrates by CDPSs, leading to the
      enzymatic production of approximately 200 non-canonical cyclodipeptides. CDPSs
      constitute an efficient enzymatic tool for the synthesis of highly diverse 2,5
      DKPs. Such diversity could be further expanded, for example, by using various
      cyclodipeptide-tailoring enzymes found in 2,5-DKP biosynthetic pathways.

PMID- 29377458
TI  - Maternal thyroid hormone is required for parvalbumin neurone development in the
      anterior hypothalamic area.
AB  - Thyroid hormone (TH) is crucial for brain development and function. This becomes
      most evident in untreated congenital hypothyroidism, leading to irreversible
      mental retardation. Likewise, maternal hypothyroxinaemia, a lack of TH during
      pregnancy, is associated with neurological dysfunction in the offspring, such as
      autism and reduced intellectual capacity. In the brain, TH acts mainly through TH
      receptor alpha1 (TRalpha1). Consequently, mice heterozygous for a dominant
      negative mutation in TRalpha1 display profound neuroanatomical abnormalities
      including deranged development of parvalbumin neurones. However, the exact timing
      and orchestration of TH signalling during parvalbumin neurone development remains
      elusive. In the present study, we dissect the development of parvalbumin neurones
      in the anterior hypothalamic area (AHA) in male mice using different mouse models
      with impaired pre- and postnatal TH signalling in combination with
      bromodeoxyuridine birth dating and immunohistochemistry. Our data reveal that
      hypothalamic parvalbumin neurones are born at embryonic day 12 and are first
      detected in the AHA at postnatal day 8, reaching their full population number at
      P13. Interestingly, they do not require TH postnatally because their development
      is not impaired in mice with impaired TH signalling after birth. By contrast,
      however, these neurones crucially depend on TH through TRalpha1 signalling in the
      second half of pregnancy, when the hormone is almost exclusively provided by the
      mother. For the first time, our findings directly link a maternal hormone to a
      neuroanatomical substrate in the foetal brain, and underline the importance of
      proper TH signalling during pregnancy for offspring mental health. Given the role
      of hypothalamic parvalbumin neurones in the central control of blood pressure,
      the present study advocates the inclusion of cardiovascular parameters in the
      current discussion on possible TH substitution in maternal hypothyroxinaemia.

PMID- 29377459
TI  - Sb Incorporation in Wurtzite and Zinc Blende InAs1-x Sbx Branches on InAs
      Template Nanowires.
AB  - The physical properties of material largely depend on their crystal structure.
      Nanowire growth is an important method for attaining metastable crystal
      structures in III-V semiconductors, giving access to advantageous electronic and
      surface properties. Antimonides are an exception, as growing metastable wurtzite
      structure has proven to be challenging. As a result, the properties of these
      materials remain unknown. One promising means of accessing wurtzite antimonides
      is to use a wurtzite template to facilitate their growth. Here, a template
      technique using branched nanowire growth for realizing wurtzite antimonide
      material is demonstrated. On wurtzite InAs trunks, InAs1-x Sbx branch nanowires
      at different Sb vapor phase compositions are grown. For comparison, branches on
      zinc blende nanowire trunks are also grown under identical conditions. Studying
      the crystal structure and the material composition of the grown branches at
      different xv shows that the Sb incorporation is higher in zinc blende than in
      wurtzite. Branches grown on wurtzite trunks are usually correlated with stacking
      defects in the trunk, leading to the emergence of a zinc blende segment of higher
      Sb content growing parallel to the wurtzite structure within a branch. However,
      the average amount of Sb incorporated within the branch is determined by the
      vapor phase composition.

PMID- 29377460
TI  - Efficient CO2 Removal for Ultra-Pure CO Production by Two Hybrid Ultramicroporous
      Materials.
AB  - Removal of CO2 from CO gas mixtures is a necessary but challenging step during
      production of ultra-pure CO as processed from either steam reforming of
      hydrocarbons or CO2 reduction. Herein, two hybrid ultramicroporous materials
      (HUMs), SIFSIX-3-Ni and TIFSIX-2-Cu-i, which are known to exhibit strong affinity
      for CO2 , were examined with respect to their performance for this separation.
      The single-gas CO sorption isotherms of these HUMs were measured for the first
      time and are indicative of weak affinity for CO and benchmark CO2 /CO selectivity
      (>4000 for SIFSIX-3-Ni). This prompted us to conduct dynamic breakthrough
      experiments and compare performance with other porous materials. Ultra-pure CO
      (99.99 %) was thereby obtained from CO gas mixtures containing both trace (1 %)
      and bulk (50 %) levels of CO2 in a one-step physisorption-based separation
      process.

PMID- 29377461
TI  - Grazing enhances belowground carbon allocation, microbial biomass, and soil
      carbon in a subtropical grassland.
AB  - Despite the large contribution of rangeland and pasture to global soil organic
      carbon (SOC) stocks, there is considerable uncertainty about the impact of large
      herbivore grazing on SOC, especially for understudied subtropical grazing lands.
      It is well known that root system inputs are the source of most grassland SOC,
      but the impact of grazing on partitioning of carbon allocation to root tissue
      production compared to fine root exudation is unclear. Given that different forms
      of root C have differing implications for SOC synthesis and decomposition, this
      represents a significant gap in knowledge. Root exudates should contribute to SOC
      primarily after microbial assimilation, and thus promote microbial contributions
      to SOC based on stabilization of microbial necromass, whereas root litter
      deposition contributes directly as plant-derived SOC following microbial
      decomposition. Here, we used in situ isotope pulse-chase methodology paired with
      plant and soil sampling to link plant carbon allocation patterns with SOC pools
      in replicated long-term grazing exclosures in subtropical pasture in Florida,
      USA. We quantified allocation of carbon to root tissue and measured root
      exudation across grazed and ungrazed plots and quantified lignin phenols to
      assess the relative contribution of microbial vs. plant products to total SOC. We
      found that grazing exclusion was associated with dramatically less overall
      belowground allocation, with lower root biomass, fine root exudates, and
      microbial biomass. Concurrently, grazed pasture contained greater total SOC, and
      a larger fraction of SOC that originated from plant tissue deposition, suggesting
      that higher root litter deposition under grazing promotes greater SOC. We
      conclude that grazing effects on SOC depend on root system biomass, a pattern
      that may generalize to other C4-dominated grasslands, especially in the
      subtropics. Improved understanding of ecological factors underlying root system
      biomass may be the key to forecasting SOC and optimizing grazing management to
      enhance SOC accumulation.

PMID- 29377462
TI  - Improvement of hepatic fibrosis and patient-reported outcomes in non-alcoholic
      steatohepatitis treated with selonsertib.
AB  - BACKGROUND: Patient-reported outcomes (PROs) represent patients' perspective
      about their well-being. AIM: To assess PRO changes in patients with non-alcoholic
      steatohepatitis (NASH) after treatment with selonsertib (SEL) and to associate
      them with different biomarkers. METHODS: Patients with NASH and stage 2-3
      fibrosis received SEL 6 mg or 18 mg orally QD alone or in combination with
      simtuzumab (SIM, 125 mg SC weekly) or SIM alone for 24 weeks. Biopsies were
      obtained at baseline and at treatment week 24. PROs were assessed using SF-36,
      CLDQ and WPAI:SHP. RESULTS: Seventy-two patients with NASH were included (54 +/-
      10 years, 31% male, 65% stage 3, 71% diabetes). Baseline physical health-related
      PRO scores were significantly lower than population norms (P < .05). During
      treatment, there were no consistent differences in treatment-emergent PRO changes
      between different regimens (P > .05). However, NASH subjects who experienced >=2
      decrease in NAFLD Activity Score or >=1-stage reduction in fibrosis showed
      significant improvements in their PROs (up to +15.5% of a PRO range size, P <
      .05). Additionally, improvements in PROs (up to +21.5%, P < .05) were noted in
      patients with at least 50% relative reduction in collagen, while NASH subjects
      with >17% increase in their collagen experienced PRO worsening (up to -13.9%, P <
      .05). Baseline serum CK-18, IL-6 and CRP significantly correlated with PROs (rho
      from -0.24 to -0.38, P < .05). CONCLUSIONS: A decrease in hepatic collagen is the
      most prominently associated with improvement of PROs in NASH patients with F2-F3
      treated with SEL. Furthermore, serum cytokines are associated with baseline PROs
      and with treatment-emergent changes in PROs in patients with NASH.

PMID- 29377463
TI  - Physical exosome:exosome interactions.
AB  - Exosomes are extracellular nanovesicles that mediate a number of cellular
      processes, including intracellular signalling. There are many published examples
      of exosome-exosome dimers; however, their relevance has not been explored. Here,
      we propose that cells release exosomes to physically interact with incoming
      exosomes, forming dimers that we hypothesize attenuate incoming exosome-mediated
      signalling. We discuss experiments to test this hypothesis and potential
      relevance in health and disease.

PMID- 29377464
TI  - Efficacy of generic oral directly acting agents in patients with hepatitis C
      virus infection.
AB  - Novel direct-acting antivirals (DAAs) are now the standard of care for the
      management of hepatitis C virus (HCV) infection. Branded DAAs are associated with
      high sustained virological response at 12 weeks post-completion of therapy
      (SVR12), but are costly. We aimed to assess the efficacy of generic oral DAAs in
      a real-life clinical scenario. Consecutive patients with known HCV infection who
      were treated with generic-oral DAA regimens (May 2015 to January 2017) were
      included. Demographic details, prior therapy and SVR12 were documented. Four
      hundred and ninety patients (mean age: 38.9 +/- 12.7 years) were treated with
      generic DAAs in the study time period. Their clinical presentations included
      chronic hepatitis (CHC) in 339 (69.2%) of cases, compensated cirrhosis in 120
      (24.48%) cases and decompensated cirrhosis in 31 (6.32%) cases. Genotype 3 was
      most common (n = 372, 75.9%) followed by genotype 1 (n = 97, 19.8%). Treatment
      naive and treatment-experienced (defined as having previous treatment with
      peginterferon and ribavirin) were 432 (88.2%) and 58 (11.8%), respectively.
      Generic DAA treatment regimens included sofosbuvir in combination with ribavirin
      (n = 175), daclatasvir alone (n = 149), ribavirin and peginterferon (n = 80),
      ledipasvir alone (n = 43), daclatasvir and ribavirin (n = 37), and ledipasvir and
      ribavirin (n = 6). Overall SVR12 was 95.9% (470/490) for all treatment regimens.
      SVR12 for treatment naive and experienced patients was 97.0% (419/432) and 87.9%
      (51/58), respectively, P = .005. High SVR12 was observed with various regimens,
      irrespective of genotype and underlying liver disease status. There were no
      differences in SVR12 with 12 or 24 weeks therapy. No major adverse event occurred
      requiring treatment stoppage. Generic oral DAAs are associated with high SVR
      rates in patients with HCV infection in a real-life clinical scenario.

PMID- 29377465
TI  - Impact of routine surveillance biopsy intensity on the diagnosis of moderate to
      severe cellular rejection and survival after pediatric heart transplantation.
AB  - Data are lacking on RSB intensity and outcomes after pediatric heart
      transplantation. PHTS centers received a survey on RSB practices from 2005 to
      present. PHTS data were obtained for 2010-2013 and integrated with center-matched
      survey responses for analysis. Survey response rate was 82.6% (38/46). Centers
      were classified as low-, moderate-, and high-intensity programs based on RSB
      frequency (0-more than 8 RSB/y). RSB intensity decreased with increasing time
      from HT. Age at HT impacted RSB intensity mostly in year 1, with little to no
      impact in later years. Most centers have not replaced RSB with non-invasive
      methods, but many added ECHO and biomarker monitoring. Higher RSB intensity was
      not associated with decreased 4-year mortality (P=.63) or earlier detection of
      moderate to severe (ISHLT grade 2R/3R) cellular rejection (RSBMSR) in the first
      year (P=.87). First-year RSBMSR incidence did not differ with intensity or age at
      HT. Significant variability exists in RSB intensity, but with no impact on timing
      and incidence of RSBMSR or 4-year mortality. Reduction in RSB frequency may be
      safe in certain patients after pediatric HT.

PMID- 29377466
TI  - Encapsulation of Crabtree's Catalyst in Sulfonated MIL-101(Cr): Enhancement of
      Stability and Selectivity between Competing Reaction Pathways by the MOF Chemical
      Microenvironment.
AB  - Crabtree's catalyst was encapsulated inside the pores of the sulfonated MIL
      101(Cr) metal-organic framework (MOF) by cation exchange. This hybrid catalyst is
      active for the heterogeneous hydrogenation of non-functionalized alkenes either
      in solution or in the gas phase. Moreover, encapsulation inside a well-defined
      hydrophilic microenvironment enhances catalyst stability and selectivity to
      hydrogenation over isomerization for substrates bearing ligating functionalities.
      Accordingly, the encapsulated catalyst significantly outperforms its homogeneous
      counterpart in the hydrogenation of olefinic alcohols in terms of overall
      conversion and selectivity, with the chemical microenvironment of the MOF host
      favouring one out of two competing reaction pathways.

PMID- 29377468
TI  - A qualitative analysis of patient-identified adaptive behaviour changes following
      interdisciplinary Acceptance and Commitment Therapy for chronic pain.
AB  - BACKGROUND: Interdisciplinary treatment programmes for chronic pain have strong
      evidence of treatment effect both immediately after treatment and at follow-up.
      However, despite strong outcome evidence, it is less clear which specific changes
      in behaviour are most relevant to patients or to outcomes. Indeed, it is not
      unknown for clinicians and patients to have different views with regard to goals
      of treatment. This study sought to evaluate the patients' perspective regarding
      important behavioural changes that occurred while they were enrolled in a 4-week
      interdisciplinary programme of Acceptance and Commitment Therapy (ACT) for
      chronic pain. METHODS: Qualitative data were collected during a treatment session
      towards the end of treatment. In total, 104 completers from 16 consecutive
      treatment groups contributed to a data set consisting of 315 unique qualitative
      comments. RESULTS: Thematic analysis resulted in a theme hierarchy including
      overarching themes, midlevel themes and subthemes. Three overarching themes were
      identified as follows: (1) interacting with self - describing an interplay
      between various aspects of the individual, (2) activity - concerning how
      individuals practically and sustainably undertook activities and (3) interacting
      with others - exploring relationships with other people. The results section
      further describes the midlevel and subthemes that cluster under the overarching
      themes. CONCLUSIONS: These data provide initial insights into the patient's
      perspective of adaptive behavioural changes gained as part of an
      interdisciplinary programme of chronic pain rehabilitation. Overall, the data
      suggest the importance of a mix of both ACT-specific and more universal
      coping/pain rehabilitation elements. Future research may examine how these
      processes relate more directly to treatment outcome. SIGNIFICANCE: This study
      provides new qualitative insights into the patient's perspective of adaptive
      behavioural changes gained as part of interdisciplinary pain rehabilitation. This
      and future work may help provide a more detailed understanding of the processes
      and behaviours that result in successful rehabilitation outcomes.

PMID- 29377467
TI  - WRKY1 acts as a key component improving resistance against Alternaria solani in
      wild tomato, Solanum arcanum Peralta.
AB  - Early blight (EB), caused by Alternaria solani, is a major threat to global
      tomato production. In comparison with cultivated tomato (Solanum lycopersicum), a
      wild relative, S. arcanum exhibits strong resistance against EB. However,
      molecular cascades operating during EB resistance in wild or cultivated tomato
      plants are largely obscure. Here, we provide novel insight into spatio-temporal
      molecular events in S. arcanum against A. solani. Transcriptome and co-expression
      analysis presented 33-WRKYs as promising candidates of which 12 SaWRKYs displayed
      differential expression patterns in resistant and susceptible accessions during
      EB disease progression. Among these, SaWRKY1 exhibited induced expression with
      significant modulation in xyloglucan endotrans hydrolase 5 (XTH5) and MYB2
      expressions that correlated with the disease phenotypes. Electro-mobility shift
      assay confirmed physical interaction of recombinant SaWRKY1 to SaXTH5 and SaMYB2
      promoters. Comparative WRKY1 promoter analysis between resistant and susceptible
      plants revealed the presence of crucial motifs for defence mechanism exclusively
      in resistant accession. Additionally, many defence-related genes displayed
      significant expression variations in both the accessions. Further, WRKY1
      overexpressing transgenic plants exhibited higher levels of EB resistance while
      RNAi silencing lines had increased susceptibility to A. solani with altered
      expression of XTH5 and MYB2. Overall, these findings demonstrate the positive
      influence of WRKY1 in improving EB resistance in wild tomato and this could be
      further utilized as a potential target through genetic engineering to augment
      protection against A. solani in crop plants.

PMID- 29377469
TI  - Component-resolved diagnostics demonstrates that most peanut-allergic individuals
      could potentially introduce tree nuts to their diet.
AB  - BACKGROUND: Nut allergy varies from pollen cross-allergy, to primary severe
      allergy with life-threatening symptoms. The screening of IgE antibodies to a wide
      spectrum of allergens, including species-specific and cross-reactive allergens,
      is made possible via microarray analysis. OBJECTIVE: We sought to study the
      association of variable IgE sensitization profiles to clinical response in peanut
      challenged children and adolescents in a birch-endemic region. In addition, we
      studied the avoidance of tree nuts and species-specific sensitizations. METHODS:
      We studied 102 peanut-sensitized patients who underwent a double-blind placebo
      controlled challenge to peanut. We analysed ISAC ImmunoCAP microarray to 112
      allergens, singleplex ImmunoCAPs for hazelnut Cor a 14 and cashew Ana o 3, and
      performed skin prick tests to peanut, tree nuts and sesame seed. We surveyed
      avoidance diets with a questionnaire. RESULTS: Sensitization to PR-10 proteins
      was frequent (Bet v 1 90%), but equally high in the challenge negatives and
      positives. IgE to Ara h 2 and Ara h 6 discriminated peanut allergic (n = 69) and
      tolerant (n = 33) the best. Avoidance of tree nuts was common (52% to 96%), but
      only 6% to 44% presented species-specific sensitizations to tree nuts, so a great
      number could potentially introduce these species into their diet. CONCLUSIONS AND
      CLINICAL RELEVANCE: PR-10-sensitizations were frequent and strong regardless of
      peanut allergy status. Component-resolved diagnostics can be employed to
      demonstrate to patients that sensitization to seed storage proteins of tree nuts
      is uncommon. Several tree nuts could potentially be reintroduced to the diet.

PMID- 29377470
TI  - Care and support for older adults in The Netherlands living independently.
AB  - The growth in the numbers of older adults needing long-term care has resulted in
      rising costs which have forced the Dutch government to change its long-term care
      system. Now, the local authorities have greater responsibility for supporting
      older adults and in prolonging independent living with increased support provided
      by the social network. However, it is unclear whether these older adults have
      such a network to rely upon. The objective of this study was to gain insight into
      the providers of formal and informal care to older adults, and to assess possible
      differences between older adults who are frail and those who are not. In
      addition, we investigated their care and support needs. We used data from a
      quantitative survey using a cross-sectional design in different regions of the
      Netherlands from July until September 2014 (n = 181). Frailty was measured using
      the Tilburg Frailty indicator. To analyse the data chi-square tests, crosstabs
      and odds ratios were used for dichotomous data and the Mann-Whitney U-Test for
      nominal data. The number of formal care providers involved was significantly
      higher (median = 2) for those deemed frail than for those not deemed frail
      (median = 1), U = 2,130, p < .005. However, more than one-third of the
      respondents deemed frail did not get the care or support they needed (33.7%).
      There was a significant positive association between being frail and having an
      informal care provider (chi2  = 18.78, df = 1, p < .005). However, more than one
      third of those deemed frail did not have an informal care provider (36.8%). One
      third of older adults deemed to be frail did not have their needs sufficiently
      addressed by their care network. For a substantial part of this group of older
      adults, the informal network seems to be unable to support them sufficiently.
      Additional attention for their needs and wishes is required to implement the
      policy reforms successfully.

PMID- 29377472
TI  - The impact of illness-related shame on psychological health and social
      relationships: Testing a mediational model in students with chronic illness.
AB  - This study explores the impact of illness-related shame on the quality of social
      relationships and psychological health in chronic patients. We aimed to examine
      the roles of fear of receiving compassion from others and experiential avoidance
      as potential mediators of this relationship. Although some studies have
      demonstrated the negative impact of chronic illness-related shame on
      psychological functioning, the mechanisms that may underlie this link remain
      understudied. The sample was comprised by 115 college students, which had been
      diagnosed with at least 1 chronic illness. Participants completed self-report
      measures on an online platform. This study's design was cross-sectional. A path
      analysis was conducted using structural equation modelling. Results showed that
      the impact of illness-related shame on both psychological health (R2  = .45) and
      the quality of social relationships (R2  = .33) was fully accounted by fear of
      compassion from others and experiential avoidance. This model revealed an
      excellent fit. Fear of receiving compassion from others was the main mediator of
      the illness-related shame link with the quality of social relationships (beta = 
      .22). The main mediator of the association between shame-related chronic illness
      and psychological health was experiential avoidance (beta = -.21).This study shed
      light on possible psychological mechanisms linking feelings of shame associated
      with having a chronic condition and impaired social relationships and mental
      health. On one hand, resisting feelings of compassion and care from others and,
      on the other hand, avoiding difficult internal experiences and situations that
      might trigger them seem to underlie the impact of shame on psychological and
      social functioning in chronic patients.

PMID- 29377471
TI  - AmotP130 regulates Rho GTPase and decreases breast cancer cell mobility.
AB  - Angiomotin (Amot) is a newly discovered, multifunctional protein that is involved
      in cell migration and angiogenesis. However, the role of its isoform, AmotP130,
      in the regulation of cytoskeleton and metastasis of breast cancer, is unclear.
      The aim of this study was to investigate the role of AmotP130 in the
      reorganization of the actin cytoskeleton and the changes of morphology in breast
      cancer cells through the Rho pathway that influences the invasion and migration
      of cells. The results suggested that AmotP130 suppressed the invasion ability
      through remodelling the cytoskeleton of breast cancer cells, including the actin
      fibre organization and focal adhesion protein turnover. Global transcriptome
      changes in breast cancer cells following knockdown of AmotP130 identified
      pathways related with the cytoskeleton and cell motility that involved the Rho
      GTPase family. From database analyses, changes in the Rho GTPase family of
      proteins were identified as possible prognostic factors in patients with breast
      cancer. We have been suggested that AmotP130 suppressed the invasion ability
      through remodelling of the cytoskeleton of breast cancer cells, involving
      regulation of the Rho pathway. The cytoskeleton-related pathway components may
      provide novel, clinically therapeutic targets for breast cancer treatment.

PMID- 29377473
TI  - Effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal
      antibodies on new-onset diabetes mellitus and glucose metabolism: A systematic
      review and meta-analysis.
AB  - AIMS: To investigate the effect of two clinically applied proprotein convertase
      subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs) on glycaemia and new
      onset diabetes mellitus (NODM). MATERIALS AND METHODS: PubMed, MEDLINE, Embase,
      Cochrane databases and ClinicalTrials.gov websites were systematically searched
      for randomized controlled trials that reported data on fasting plasma glucose
      (FPG), glycated haemoglobin (HbA1c) or NODM incidence. Risk ratios (RRs) for NODM
      and mean difference (MD) for FPG and HbA1c with 95% confidence intervals (CIs)
      were calculated using a fixed-effect model. Heterogeneity was examined using the
      I2 statistic and potential publication bias was assessed using funnel plots and
      Egger's test. RESULTS: A total of 18 studies including 26 123 participants
      without diabetes were identified. No significant difference was observed in the
      PCSK9-mAb treatment groups in terms of NODM (RR 1.05, 95% CI 0.95-1.16), FPG (MD
      0.00 mmol/L, 95% CI -0.02 to 0.02) or HbA1c (MD 0.00% [0 mmol/L], 95% CI -0.01 to
      0.01) compared with control groups. Subgroup (PCSK9-mAb type, participant
      characteristics, treatment duration, treatment method and differences in control
      treatment) and sensitivity analyses did not significantly alter the results. Meta
      regression analyses showed that risk of NODM was not associated with baseline
      age, baseline body mass index (BMI), proportion of men, treatment duration or
      percent LDL cholesterol reduction. CONCLUSIONS: Alirocumab and evolocumab, two
      types of PCSK9-mAb approved by the US Food and Drug Administration and the
      European Medicines Agency, had no significant impact on NODM and glucose
      homeostasis, regardless of PCSK9-mAb type, participant characteristics, treatment
      duration, treatment method and differences in control treatment. Baseline age,
      BMI, proportion of men, treatment duration, and percent change of LDL cholesterol
      did not influence diabetes risk.

PMID- 29377474
TI  - A prospective randomized, controlled trial of eculizumab to prevent ischemia
      reperfusion injury in pediatric kidney transplantation.
AB  - Ischemia-reperfusion injury has multiple effects on a transplanted allograft,
      including delayed or impaired graft function, compromised long-term survival, and
      an association with an increased incidence of rejection. Eculizumab, a monoclonal
      antibody blocking terminal complement activation, has been postulated to be an
      effective agent in the prevention or amelioration of IRI. We performed a single
      center prospective, randomized controlled trial involving 57 pediatric kidney
      transplant recipients between 2012 and 2016. The immunosuppressive protocol
      included two doses of alemtuzumab; half of the patients were randomized to
      receive a single dose of eculizumab prior to transplantation. Maintenance
      immunosuppression was based on a combination of low-dose tacrolimus and
      mycophenolate, without steroids. Eculizumab-treated patients had a significantly
      better early graft function, less arteriolar hyalinosis and chronic
      glomerulopathy on a protocol biopsies taken on day 30, 1 year, and 3 years after
      transplantation. In the eculizumab group, four non-vaccinated children lost their
      grafts during the course of a flu-like infection. Eculizumab is associated with
      better early graft function and improved graft morphology; however, there was an
      unacceptably high number of early graft losses among the eculizumab-treated
      children. While a promising strategy, the best approach to complement inhibition
      remains to be established.

PMID- 29377475
TI  - Preservation and augmentation of molar extraction sites affected by severe bone
      defect due to advanced periodontitis: A prospective clinical trial.
AB  - BACKGROUND: Studies of the extracted infected-molar ridge preservation are
      limited. PURPOSE: To compare alterations of hard and soft tissue in infected
      molar sockets receiving ridge preservation compared with natural healing.
      MATERIALS AND METHODS: Thirty-five infected-molar extraction sites either
      preserving with Bio-Gide membrane covered the Bio-Oss material or receiving
      natural healing procedure as controls. The soft tissue profile was evaluated
      before tooth extraction and after 6-month healing. Cone-beam computed tomography
      scans were taken immediately and 6 months after extraction. Vertical and
      horizontal bone changes were assessed radiographically. Data were analyzed with
      Mann-Whitney U test and alpha = 0.05. RESULTS: No significant differences in soft
      tissue and vertical bone changes in the medium region of the sockets were found
      (P > .05). Buccal bone changes in the mesial and distal sites in the test group
      were significantly lower than the control group (P < .05). Ridge width increased
      from 0.21mm to 5.30mm at 1mm apical from the crest in the test and reduced from
      0.12 mm to 1.00 mm in the control groups. CONCLUSION: Ridge preservation at
      periodontally compromised molar extraction sites might compensate for ridge width
      and buccal bone resorption that occurs with natural healing alone.

PMID- 29377476
TI  - COMP Report: CPQR technical quality control guidelines for CyberKnife(r)
      Technology.
AB  - The Canadian Organization of Medical Physicists (COMP), in close partnership with
      the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series
      of Technical Quality Control (TQC) guidelines for radiation treatment equipment.
      These guidelines outline the performance objectives that equipment should meet in
      order to ensure an acceptable level of radiation treatment quality. This
      particular TQC contains detailed performance objectives and safety criteria for
      CyberKnife(r) Technology. The quality control recommendations in this document
      are based upon previously published guidelines and the collective experience of
      all Canadian sites using this technology. This TQC guideline has been field
      tested at the newest Canadian CyberKnife installation site and includes
      recommendations for quality control of the IrisTM and InCiseTM MLC collimation
      systems.

PMID- 29377477
TI  - Regulation of Charge Carrier Dynamics in ZnO Microarchitecture-Based UV/Visible
      Photodetector via Photonic-Strain Induced Effects.
AB  - A feasible, morphological influence on photoresponse behavior of ZnO
      microarchitectures such as microwire (MW), coral-like microstrip (CMS), fibril
      like clustered microwire (F-MW) grown by one-step carrier gas/metal catalyst
      "free" vapor transport technique is reported. Among them, ZnO F-MW exhibits
      higher photocurrent (IPh ) response, i.e., IPh/ZnO F-MW > IPh/ZnO CMS > IPh/ZnO
      MW . The unique structural alignment of ZnO F-MW has enhanced the IPh from 14.2
      to 186, 221, 290 uA upon various light intensities such as 0 to 6, 11, 17 mW cm-2
      at lambda405 nm . Herein, the nature of the as-fabricated ZnO photodetector (PD)
      is also demonstrated modulated by tuning the inner crystals piezoelectric
      potential through the piezo-phototronic effect. The IPh response of PD decreases
      monotonically by introducing compressive strain along the length of the device,
      which is due to the synergistic effect between the induced piezoelectric
      polarization and photogenerated charge carriers across the metal-semiconductor
      interface. The current behavior observed at the two interfaces acting as the
      source (S) and drain (D) is carefully investigated by analyzing the Schottky
      barrier heights (PhiSB ). This work can pave the way for the development of
      geometrically modified strain induced performances of PD to promote next
      generation self-powered optoelectronic integrated devices and switches.

PMID- 29377479
TI  - Dipyrone is the preferred nonopioid analgesic for the treatment of acute and
      chronic pain. A survey of clinical practice in German-speaking countries.
AB  - PURPOSE: Nonopioid analgesics are frequently used for the treatment of acute and
      chronic pain. Dipyrone is an alternative to NSAIDs and paracetamol, however, data
      on the frequency of its usage by anaesthesiologists in the perioperative and
      chronic pain setting are lacking and its adverse reactions are a matter of
      debate. METHODS: The link to a questionnaire on the use of nonopioid analgesics
      (NSAIDs, COX-2 inhibitors, paracetamol, dipyrone) and the safety of dipyrone in
      the perioperative and chronic pain setting was mailed to anaesthesiologists and
      pain physicians. RESULTS: A total of 2237 responses were analysed. About 97.4% of
      the respondents used nonopioid analgesics for the treatment of acute pain, with
      93.8% administering dipyrone, 54.0% NSAIDs, 41.8% COX-2 inhibitors and 49.2%
      paracetamol. Nonopioid analgesics were administered preoperatively by 22.3%,
      intraoperatively by 86.1% and postoperatively by 73.0% of the respondents. For
      chronic pain management, 76.7% of the respondents prescribed oral dipyrone in
      combination with other nonopioid analgesics; 19.9% used dipyrone as sole
      nonopioid, whereas 2.9% denied its use. Cases of dipyrone-associated
      agranulocytosis were observed by 3.5% of the respondents of the acute and 1.5% of
      the chronic pain questionnaire, respectively. The majority of respondents (acute
      pain: 73.0%, chronic pain 59.3%) performed no blood cell counts to monitor
      dipyrone therapy. Patients were rarely informed about possible adverse drug
      reactions. CONCLUSIONS: Dipyrone is the preferred nonopioid analgesic in the
      perioperative and chronic pain setting. Although cases of agranulocytosis occur,
      benefits apparently outweigh the risks according to anaesthesiologists. Measures
      like patient information may improve safety. SIGNIFICANCE: A survey of
      anaesthesiologist in German-speaking countries revealed dipyrone as preferred
      nonopioid analgesic for the treatment of acute and chronic pain. Benefits seem to
      outweigh the risks, specifically the risk of agranulocytosis. Information of
      medical staff and patients on adverse drug reactions and symptoms of
      agranulocytosis should be implemented.

PMID- 29377480
TI  - Chemical Research Society of India Awards 2018.

PMID- 29377478
TI  - Independent mapping methods reveal rotational activation near pulmonary veins
      where atrial fibrillation terminates before pulmonary vein isolation.
AB  - OBJECTIVE: To investigate mechanisms by which atrial fibrillation (AF) may
      terminate during ablation near the pulmonary veins before the veins are isolated
      (PVI). INTRODUCTION: It remains unstudied how AF may terminate during ablation
      before PVs are isolated, or how patients with PV reconnection can be arrhythmia
      free. We studied patients in whom PV antral ablation terminated AF before PVI,
      using two independent mapping methods. METHODS: We studied patients with AF
      referred for ablation, in whom biatrial contact basket electrograms were studied
      by both an activation/phase mapping method and by a second validated mapping
      method reported not to create false rotational activity. RESULTS: In 22 patients
      (age 60.1 +/- 10.4, 36% persistent AF), ablation at sites near the PVs terminated
      AF (77% to sinus rhythm) prior to PVI. AF propagation revealed rotational (n  = 
      20) and focal (n  =  2) patterns at sites of termination by mapping method 1 and
      method 2. Both methods showed organized sites that were spatially concordant (P <
      0.001) with similar stability (P < 0.001). Vagal slowing was not observed at
      sites of AF termination. DISCUSSION: PV antral regions where ablation terminated
      AF before PVI exhibited rotational and focal activation by two independent
      mapping methods. These data provide an alternative mechanism for the success of
      PVI, and may explain AF termination before PVI or lack of arrhythmias despite PV
      reconnection. Mapping such sites may enable targeted PV lesion sets and improved
      freedom from AF.

PMID- 29377481
TI  - Correlation between septal body size and inferior turbinate hypertrophy on
      computerised tomography scans in fifty patients: A radiological analysis.

PMID- 29377482
TI  - Understanding of diagnosis and medications among non-English-speaking older
      patients.
AB  - OBJECTIVE: To determine whether non-English-speaking background (NESB) patients
      had a poorer understanding of diagnosis and medications compared to English
      speaking background (ESB) patients. METHODS: English-speaking background and NESB
      patients admitted to inpatient geriatric evaluation and management (GEM) unit
      were asked standardised questions about their admission diagnosis, reason for GEM
      admission and medications. Accuracy of answers, as compared to medical notes,
      ranked as 'full credit', 'partial credit' or 'no credit'. RESULTS: Of the 66
      patients recruited (30 NESB), understanding of diagnosis and purpose of GEM
      admission was good. There was no difference between ESB and NESB patients.
      Understanding of medications taken prior to admission was poor, with 67% of
      overall patients scoring 'no credit'. NESB patients were more likely to score 'no
      credit' compared to ESB (80% vs 56%, P = 0.036). CONCLUSION: Reassuringly,
      patients had a reasonable understanding of diagnosis and purpose of GEM
      admission. Lack of understanding of medications, especially among NESB patients,
      should be improved.

PMID- 29377484
TI  - Broadening the Scope for Fluoride-Free Synthesis of Siliceous Zeolites.
AB  - Siliceous zeolites are ideally suited for emerging applications in gas
      separations, sensors, and the next generation of low-k dielectric materials, but
      the use of fluoride in the synthesis significantly hinders their
      commercialization. Herein, we show that the dry gel conversion (DGC) technique
      can overcome this problem. Fluoride-free synthesis of two siliceous zeolites-AMH
      4 (CHA-type) and AMH-5 (STT-type), has been achieved for the first time using the
      method. Siliceous *BEA-, MFI-, and *MRE-type zeolites have also been synthesized
      to obtain insights into the crystallization process. Charge-balancing
      interactions between the inorganic cation, organic structure-directing agent
      (OSDA), and Si-O- defects are found to be an essential aspect. We quantify this
      factor in terms of the "OSDA charge/silica ratio" of the as-made zeolites and
      demonstrate that the DGC technique is broadly applicable and opens up new avenues
      for fluoride-free siliceous zeolite synthesis.

PMID- 29377483
TI  - 'To be treated as a human': Using co-production to explore experts by experience
      involvement in mental health nursing education - The COMMUNE project.
AB  - Increasingly, experts as deemed by personal experience or mental health service
      use, are involved in the education of nurses; however, accompanying research is
      limited and focuses primarily on opinions of nurse educators and students. The
      aim of this study was to develop an understanding of the potential contribution
      to mental health nursing education by those with experience of mental health
      service use. The research was part of the international COMMUNE (Co-production of
      Mental Health Nursing Education) project, established to develop and evaluate co
      produced mental health content for undergraduate nursing students. A qualitative
      descriptive design was adopted with data collected through focus group interviews
      in seven sites across Europe and Australia. Experts by experience (people with
      experience of distress, service use, and recovery) co-produced the project in
      partnership with nursing academics. Co-production enriched the process of data
      collection and facilitated the analysis of data from multiple perspectives. Two
      themes are presented in this paper. The first focuses on how experts by
      experience can enhance students' understanding of recovery by seeing the
      strengths inherent in the 'human' behind the diagnostic label. The second
      highlights the importance of communication and self-reflection on personal
      values, where students can explore their own thoughts and feelings about mental
      distress alongside those with lived experience. Interacting with experts by
      experience in the classroom can assist in challenging stigmatizing attitudes
      prior to nursing placements. These findings can be used to inform international
      nursing curricula by increasing the focus on nursing skills valued by those who
      use the services.

PMID- 29377485
TI  - Protistology Conferences: The Beginnings. The First International Protozoology
      Conference (Prague 1961) and the Tribute to Otto Jirovec, its Spiritual Father.
AB  - Two events have helped to shape protozoology/protistology as a specific
      scientific discipline. The first such event was the creation of the Society of
      Protozoologists in the U.S. in 1947 (and of its Journal of Protozoology, first
      published in 1954), the second event was the First International Conference on
      Protozoology, held in 1961 in Prague. The history of the Society of
      Protozoologists was comprehensively treated by Corliss (1998); the history of the
      Prague Conference is presented here as reminiscences and personal interpretation
      of events of the author, who was one of the conference organizers and a member of
      the organization committee. Special attention is given to the personality and
      scientific accomplishments of Otto Jirovec, the 1961 conference spiritual father
      and president. It is concluded that the Prague Conference, while establishing the
      tradition of protistology meetings, helped protistology to attain its present
      status as a fundamental science discipline, which discovers and interprets the
      web of life at one of its, basic, "microbial" levels. Protists literally permeate
      the earth biosphere and in a way represent the "dark matter" of the living world,
      still awaiting many discoveries.

PMID- 29377486
TI  - Liver atrophy and regeneration in noncirrhotic portal vein thrombosis: Effect of
      surgical shunts.
AB  - The goal of the study is to characterize the relationship between portal vein
      thrombosis (PVT) and hepatic atrophy in patients without cirrhosis and the effect
      of various types of surgical shunts on liver regeneration and splenomegaly.
      Patients without cirrhosis with PVT suffer from presinusoidal portal
      hypertension, and often hepatic atrophy is a topic that has received little
      attention. We hypothesized that patients with PVT have decreased liver volumes,
      and shunts that preserve intrahepatic portal flow enhance liver regeneration.
      Sixty-four adult and pediatric patients with PVT who underwent surgical shunt
      placement between 1998 and 2011 were included in a retrospective study. Baseline
      liver volumes from adult patients were compared with standard liver volume (SLV)
      as well as a group of healthy controls undergoing evaluation for liver donation.
      Clinical assessment, liver function tests, and liver and spleen volumes from
      cross-sectional imaging were compared before and after surgery. A total of 40
      patients received portal flow-preserving shunts (32 mesoportal and 8 selective
      splenorenal), whereas 24 received portal flow-diverting shunts (16 nonselective
      splenorenal and 8 mesocaval). Baseline adult liver volumes were 26% smaller than
      SLV (1248 versus 1624 cm3 ; P = 0.02) and 20% smaller than the control volumes
      (1248 versus 1552 cm3 ; P = 0.02). Baseline adult spleen volumes were larger
      compared with controls (1258 versus 229 cm3 ; P < 0.001). Preserving shunts were
      associated with significant increase in liver volumes (886 versus 1131 cm3 ; P =
      0.01), whereas diverting shunts were not. Diverting shunts significantly improved
      splenomegaly. In conclusion, we have demonstrated that patients without cirrhosis
      with PVT have significant liver atrophy and splenomegaly. Significant liver
      regeneration was achieved after portal flow-preserving shunts. Liver
      Transplantation 24 881-887 2018 AASLD.

PMID- 29377487
TI  - New rapid PCR protocol based on high-resolution melting analysis to identify
      Saccharomyces cerevisiae and other species within its genus.
AB  - AIMS: Selection projects aiming at the identification of new Saccharomyces
      strains are always on going as the use of the suitable yeast can strongly improve
      fermented food production, particularly winemaking. They are mainly targeted on
      Saccharomyces cerevisiae, but other species in the Saccharomyces genus are of
      interest. For this reason, more and more efficient molecular techniques for yeast
      identification able to accelerate yeast selection process are always needed.
      Among the Saccharomyces genus, four yeasts are widespread in natural
      environments: S. cerevisiae; S. uvarum; S. kudriavzevii and S. paradoxus.
      Therefore, among the Saccharomyces species, their discrimination is of great
      interest. METHODS AND RESULTS: A two-step protocol is proposed. Firstly the
      Saccharomyces genus identification is achieved by multiplex PCR analysis. Then,
      the Saccharomyces species is determined by a new method based on high-resolution
      melting analysis (HRMA). CONCLUSIONS: For HRMA two primer pairs have been
      proposed. The first was able to achieve the simultaneous identification of the
      four widespread Saccharomyces species, the second was used for the unambiguous
      discrimination of S. cerevisiae within its taxonomical genus. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This assay allowed an easy, rapid and simultaneous
      discrimination of S. cerevisiae, S. uvarum and S. paradoxus during yeast
      selection programs.

PMID- 29377488
TI  - Network spandrels reflect ecological assembly.
AB  - Ecological networks that exhibit stable dynamics should theoretically persist
      longer than those that fluctuate wildly. Thus, network structures which are over
      represented in natural systems are often hypothesised to be either a cause or
      consequence of ecological stability. Rarely considered, however, is that these
      network structures can also be by-products of the processes that determine how
      new species attempt to join the community. Using a simulation approach in tandem
      with key results from random matrix theory, we illustrate how historical assembly
      mechanisms alter the structure of ecological networks. We demonstrate that
      different community assembly scenarios can lead to the emergence of structures
      that are often interpreted as evidence of 'selection for stability'. However, by
      controlling for the underlying selection pressures, we show that these assembly
      artefacts-or spandrels-are completely unrelated to stability or selection, and
      are instead by-products of how new species are introduced into the system. We
      propose that these network-assembly spandrels are critically overlooked aspects
      of network theory and stability analysis, and we illustrate how a failure to
      adequately account for historical assembly can lead to incorrect inference about
      the causes and consequences of ecological stability.

PMID- 29377489
TI  - Large reductions in pesticides made possible by use of an insect-trapping lamp: a
      case study in a winter wheat-summer maize rotation system.
AB  - BACKGROUND: Increasing attention is being paid to physical methods to control
      pests such as insect trapping. In order to examine how pesticides can reasonably
      be combined with the use of an insect-trapping lamp and by how much this can
      reduce the amount of pesticide used, five treatments were applied to a winter
      wheat-summer maize rotation system in eastern China: a treatment in which only
      pesticides were used; a treatment with only insect-trapping lamps; insect
      trapping lamps plus one application of pesticides; insect-trapping lamps plus two
      applications of pesticides; insect-trapping lamps plus three applications of
      pesticides. RESULTS: The results showed that, when pesticides were reduced by 25
      35%, the insect-trapping lamps controlled the insect population well and yields
      were not decreased but were actually increased, with pesticides being applied
      only at 2 days before winter wheat planting, at winter wheat flowering and at the
      big flare stage of summer maize. Reducing pesticides by 35-65% had no adverse
      effect on crop yields, and thus had the potential to reduce the costs of pest
      control and produce the greatest economic benefit. When no pesticides were used
      in the insect-trapping lamp control area, the annual yield was still >15 t hm-2 .
      CONCLUSION: If pesticides are used in a timely fashion and at the appropriate
      stage, their use may be greatly reduced with the help of an insect-trapping lamp.
      (c) 2018 Society of Chemical Industry.

PMID- 29377490
TI  - Fabrication and Deformation of 3D Multilayered Kirigami Microstructures.
AB  - Mechanically guided 3D microassembly with controlled compressive buckling
      represents a promising emerging route to 3D mesostructures in a broad range of
      advanced materials, including single-crystalline silicon (Si), of direct
      relevance to microelectronic devices. During practical applications, the
      assembled 3D mesostructures and microdevices usually undergo external mechanical
      loading such as out-of-plane compression, which can induce damage in or failure
      of the structures/devices. Here, the mechanical responses of a few mechanically
      assembled 3D kirigami mesostructures under flat-punch compression are studied
      through combined experiment and finite element analyses. These 3D kirigami
      mesostructures consisting of a bilayer of Si and SU-8 epoxy are formed through
      integration of patterned 2D precursors with a prestretched elastomeric substrate
      at predefined bonding sites to allow controlled buckling that transforms them
      into desired 3D configurations. In situ scanning electron microscopy measurement
      enables detailed studies of the mechanical behavior of these structures. Analysis
      of the load-displacement curves allows the measurement of the effective stiffness
      and elastic recovery of various 3D structures. The compression experiments
      indicate distinct regimes in the compressive force/displacement curves and
      reveals different geometry-dependent deformation for the structures.
      Complementary computational modeling supports the experimental findings and
      further explains the geometry-dependent deformation.

PMID- 29377491
TI  - Van der Waals Heterostructures Comprised of Ultrathin Polymer Nanosheets for
      Efficient Z-Scheme Overall Water Splitting.
AB  - Inspired by natural photosynthesis, Z-scheme photocatalytic systems are very
      appealing for achieving efficient overall water splitting. Developing metal-free
      Z-scheme photocatalysts for overall water splitting, however, still remains
      challenging. The construction of polymer-based van der Waals heterostructures as
      metal-free Z-scheme photocatalytic systems for overall water splitting is
      described using aza-fused microporous polymers (CMP) and C2 N ultrathin
      nanosheets as O2 - and H2 -evolving catalysts, respectively. Although neither
      polymer is able to split pure water using visible light, a 2:1 stoichiometric
      ratio of H2 and O2 was observed when aza-CMP/C2 N heterostructures were used. A
      solar-to-hydrogen conversion efficiency of 0.23 % was determined, which could be
      further enhanced to 0.40 % by using graphene as the solid electron mediator to
      promote the interfacial charge-transfer process. This study highlights the
      potential of polymer photocatalysts for overall water splitting.

PMID- 29377492
TI  - COMP report: CPQR technical quality control guidelines for treatment planning
      systems.
AB  - The Canadian Organization of Medical Physicists (COMP), in close partnership with
      the Canadian Partnership for Quality Radiotherapy (CPQR) has developed a series
      of Technical Quality Control (TQC) guidelines for radiation treatment equipment.
      These guidelines outline the performance objectives that equipment should meet in
      order to ensure an acceptable level of radiation treatment quality. The TQC
      guidelines have been rigorously reviewed and field tested in a variety of
      Canadian radiation treatment facilities. The development process enables rapid
      review and update to keep the guidelines current with changes in technology. This
      article contains detailed performance objectives and safety criteria for
      Treatment Planning Systems (TPS) for External Beam Radiotherapy.

PMID- 29377493
TI  - Molecular evidence and clinical importance of beta-arrestins expression in
      patients with acromegaly.
AB  - beta-arrestins seem to have a role in endocytosis and desensitization of
      somatostatin receptor subtype 2 (sst2) and could be associated with the
      responsiveness to somatostatin receptor ligands (SRL) in patients with
      acromegaly. To investigate the in vivo correlation between beta-arrestins 1 and 2
      with sst2, sst5 and dopamine receptor subtype 2 (D2) expressions, and the
      association of beta-arrestins with response to first-generation SRL and
      invasiveness in somatotropinomas. beta-arrestins 1 and 2, sst2, sst5 and D2 mRNA
      expressions were evaluated by quantitative real-time RT-PCR on tumoral tissue of
      96 patients. Moreover, sst2 and sst5 protein expressions were also evaluated in
      40 somatotropinomas by immunohistochemistry. Response to SRL, defined as GH <1
      MUg/l and normal IGF-I levels, was assessed in 40 patients. The Knosp-Steiner
      criteria were used to define invasiveness. Median beta-arrestin 1, beta-arrestin
      2, sst2, sst5 and D2 mRNA copy numbers were 478; 9375; 731; 156; and 3989,
      respectively. There was a positive correlation between beta-arrestins 1 and 2 (R
      = 0.444, P < 0.001). However, no correlation between beta-arrestins and sst2,
      sst5 (mRNA and protein levels) or D2 was found. No association was found between
      beta-arrestins expression and SRL responsiveness or tumour invasiveness. Although
      previous data suggest a putative correlation between beta-arrestins and sst2, our
      data clearly indicated that no association existed between beta-arrestins and
      sst2, sst5 or D2 expression, nor with response to SRL or tumour invasiveness.
      Therefore, further studies are required to clarify whether beta-arrestins have a
      role in the response to treatment with SRL in acromegaly.

PMID- 29377494
TI  - Untargeted Metabolomic Screen Reveals Changes in Human Plasma Metabolite Profiles
      Following Consumption of Fresh Broccoli Sprouts.
AB  - SCOPE: Several lines of evidence suggest that the consumption of cruciferous
      vegetables is beneficial to human health. Yet, underlying mechanisms and key
      molecular targets that are involved with achieving these benefits in humans are
      still not fully understood. To accelerate this research, we conduct a human study
      to identify potential molecular targets of crucifers for further study. This
      study aims to characterize plasma metabolite profiles in humans before and after
      consuming fresh broccoli sprouts (a rich dietary source of bioactive
      sulforaphane). METHODS AND RESULTS: Ten healthy adults consume fresh broccoli
      sprouts (containing 200 MUmol sulforaphane equivalents) at time 0 and provide
      blood samples at 0, 3, 6, 12, 24, and 48 h. An untargeted metabolomics screen
      reveals that levels of several plasma metabolites are significantly different
      before and after sprout intake, including fatty acids (14:0, 14:1, 16:0, 16:1,
      18:0, and 18:1), glutathione, glutamine, cysteine, dehydroepiandrosterone, and
      deoxyuridine monophosphate. Evaluation of all time points is conducted using
      paired t-test (R software) and repeated measures analysis of variance for a
      within-subject design (Progenesis QI). CONCLUSION: This investigation identifies
      several potential molecular targets of crucifers that may aid in studying
      established and emerging health benefits of consuming cruciferous vegetables and
      related bioactive compounds.

PMID- 29377495
TI  - Cancer etiology: Variation in cancer risk among tissues is poorly explained by
      the number of gene mutations.
AB  - Recent evidence indicates that the risk of being diagnosed with cancer in a
      tissue is strongly correlated (0.80) with the number of stem cell divisions
      accumulated by the tissue. Since cell division can generate random mutations
      during DNA replication, this correlation has been used to propose that cancer is
      largely caused by the accumulation of unavoidable mutations in driver genes.
      However, no correlation between the number of gene mutations and cancer risk
      across tissues has been reported. Because many somatic mutations in cancers
      originate prior to tumor initiation and the number of cell divisions occurring
      during tumor growth is similar among tissues, I use whole genome sequencing
      information from 22 086 cancer samples and incidence data from the largest cancer
      registry in each continent to study the relationship between the number of gene
      mutations and the risk of cancer across 33 tissue types. Results show a weak
      positive correlation (mean = 0.14) between these 2 parameters in each of the 5
      cancer registries. The correlation became stronger (mean = 0.50) when gender
      related cancers were excluded. Results also show that 1003 samples from 29 cancer
      types have zero mutations in genes. These data suggest that cancer etiology can
      be better explained by the accumulation of stem cell divisions than by the
      accumulation of gene mutations. Possible mechanisms by which the accumulation of
      cell divisions in stem cells increases the risk of cancer are discussed.

PMID- 29377496
TI  - Gene transfer of a naked plasmid (pUDK-HGF) encoding human hepatocyte growth
      factor attenuates skin/muscle incision and retraction-induced chronic post
      surgical pain in rats.
AB  - BACKGROUND: Chronic post-surgical pain (CPSP) remains a major clinical problem
      and is often refractory to current treatments. New analgesic medications and
      strategies for pain relief are needed. Hepatocyte growth factor (HGF) is known to
      be a multi-functional growth factor and regulates various biological activities.
      METHODS: We investigated the analgesic effect and underlying mechanism of plasmid
      pUDK-HGF encoding human HGF gene on CPSP induced by skin/muscle incision and
      retraction (SMIR) in rats. The possible changes of inflammatory factors, glial
      cell activation and pain sensitivity after pUDK-HGF administration were
      investigated by ELISA, western blot and Von Frey tests, respectively. RESULTS: In
      behavioural assays, we found that a single intramuscular or intrathecal injection
      of pUDK-HGF significantly attenuated mechanical hypersensitivity to von Frey
      stimulation of plantar ipsilateral hind paw after SMIR. Intramuscular injection
      of pUDK-HGF promoted blood flow and proliferation of satellite cells and
      inhibited inflammatory cells recruitment, collagen accumulation and expression of
      pronociceptive factors. Intrathecal injection of pUDK-HGF inhibited activation of
      spinal glial cells and production of inflammatory mediators induced by SMIR.
      CONCLUSIONS: pUDK-HGF has a strong analgesic potency and efficacy in CPSP induced
      by SMIR in rats. This study highlights a new strategy for the treatment of CPSP.
      SIGNIFICANCE: The CPSP occurs following various surgical procedures and remains a
      major clinical problem due to the lack of study on the mechanisms of CPSP. Our
      findings provide the first evidence that pUDK-HGF attenuates SMIR-induced pain
      behaviuors through peripheral or central mechanisms. The peripheral analgesic
      effect of pUDK-HGF is associated with promoting tissue repair and inhibiting
      inflammatory response; furthermore, pUDK-HGF inhibits activation of spinal glial
      cells and overexpression of inflammatory mediators in spinal cord. Therefore,
      naked pUDK-HGF may be a potential therapeutic strategy for treatment of CPSP in
      clinic.

PMID- 29377497
TI  - Reduced Cell Division Control Protein 42 Activity Compromises Hematopoiesis
      Supportive Function of Fanconi Anemia Mesenchymal Stromal Cells.
AB  - Hematopoietic stem cells preserve their ability to self-renew and differentiate
      to different lineages in the bone marrow (BM) niche, which is composed in large
      part by BM stromal cells. Studies have shown that altered signaling in the BM
      niche results in leukemia initiation or progression. Fanconi anemia (FA) is an
      inherited BM failure syndrome associated with extremely high risk of leukemic
      transformation. By using two FA mouse models, here we have investigated the
      hematopoiesis-supportive function of FA BM mesenchymal stroma cells (MSCs). We
      found that MSCs deficient for Fanca or Fancc gene are defective in proliferation
      and prone to undergo senescence in vitro. Mechanistically, we show that the
      activity of cell division control protein 42 (Cdc42), a Rho GTPase known to be a
      critical regulator for cytoskeleton organization, is significantly reduced in FA
      MSCs. Furthermore, we demonstrate that this reduction in Cdc42 activity plays a
      causal role in defective hematopoiesis-supportive function of the FA MSCs. The
      progenies of wild-type hematopoietic stem and progenitor cells cocultured on FA
      MSCs exhibit compromised self-renewal capacity both in vitro and in vivo. Genetic
      correction of FA deficiency restores Cdc42 activity and improves the
      hematopoiesis-supportive capacity of FA MSC. Finally, ectopic expression of a
      constitutively active Cdc42 mutant, Cdc42F28L, or pretreatment with Wnt5a,
      increases the active Cdc42 level and rescues the hematopoietic supportive defects
      of FA MSCs. Taken together, our results identify a novel link between Cdc42
      activity and the hematopoiesis-supportive function of MSCs and suggest that a
      niche-specific increase of Cdc42 activity may be beneficial for FA therapy. Stem
      Cells 2018;36:785-795.

PMID- 29377498
TI  - Intrauterine growth restriction is not associated with decreased exercise
      capacity in adolescents with congenital heart disease.
AB  - OBJECTIVE: Multiple studies demonstrate the association of intrauterine growth
      restriction (IUGR) with impaired aerobic fitness in adolescents and adults. To
      our knowledge, there are no studies including individuals with the history of
      both IUGR and congenital heart disease (CHD). Thus, we sought to evaluate the
      impact of IUGR on exercise capacity in adolescents with CHD. STUDY DESIGN: We
      conducted a retrospective chart review of patients <18 years of age who underwent
      cardiopulmonary exercise testing (CPET) between August 1, 2003 and July 1, 2016.
      Individuals with birth weight <10th percentile for gestational age were defined
      as IUGR. Patients with IUGR were matched with non-IUGR patients by cardiac
      diagnosis and age at CPET. We excluded patients >18 years of age at time of CPET,
      those without a documented birth weight, gestational age, or Race. RESULTS: A
      total of 282 patients were included with CHD present in 86 IUGR cases and 86
      controls. There was no difference in percent predicted exercise duration (IUGR:
      65.2% +/- 31.2, non-IUGR: 67.4% +/- 27.2; P = .67). Resting heart rate,
      chronotropic index, percent-predicted peak oxygen consumption, and pulmonary
      function were similar between groups. Regression analyses confirmed that IUGR was
      not independently associated with difference in percent-predicted exercise
      duration. CONCLUSIONS: Intrauterine growth restriction is not associated with the
      differences in the measurements of exercise capacity in adolescents with CHD.
      These findings contrast earlier studies, showing decreased fitness in individuals
      with low birth weight but without CHD. To our knowledge, this is the first study
      to examine the impact of IUGR on exercise capacity in patients with CHD.

PMID- 29377499
TI  - Local Surface Structure and Composition Control the Hydrogen Evolution Reaction
      on Iron Nickel Sulfides.
AB  - In order to design more powerful electrocatalysts, developing our understanding
      of the role of the surface structure and composition of widely abundant bulk
      materials is crucial. This is particularly true in the search for alternative
      hydrogen evolution reaction (HER) catalysts to replace platinum. We report
      scanning electrochemical cell microscopy (SECCM) measurements of the (111)
      crystal planes of Fe4.5 Ni4.5 S8 , a highly active HER catalyst. In combination
      with structural characterization methods, we show that this technique can reveal
      differences in activity arising from even the slightest compositional changes. By
      probing electrochemical properties at the nanoscale, in conjunction with
      complementary structural information, novel design principles are revealed for
      application to rational material synthesis.

PMID- 29377500
TI  - Neutrophil-to-lymphocyte ratio predicts anastomotic dehiscence.
AB  - BACKGROUND: Anastomotic dehiscence (AD) is the most feared complication following
      colonic and rectal anastomosis. Multiple attempts have been made to correlate the
      levels of biomarkers to the risk of AD. This study attempts to compare C-reactive
      protein (CRP), procalcitonin (PCT) and neutrophil-to-lymphocyte ratio (NLR) as
      predictors of AD. METHOD: This case-controlled study collected data on patients
      undergoing colonic and rectal anastomosis over an 18-month period. Levels of CRP,
      PCT and NLR were recorded daily for the first 5 days post-operatively. These
      results were then compared between those who developed AD and those who did not.
      RESULTS: A total of 136 patients were included; 11 (8.1%) patients developed AD.
      CRP and NLR were useful predictors of AD with an area under the curve of 0.81 and
      0.78 on post-operative day 4. PCT was not found to be raised significantly higher
      in patients who developed AD compared to those who did not. CONCLUSION: CRP and
      NLR are useful predictors of AD. PCT is not a useful predictor of AD.

PMID- 29377501
TI  - Reply to: 'High stoma prevalence and stoma reversal complications following
      anterior resection for rectal cancer: a population-based multicentre study'.

PMID- 29377502
TI  - Temporal variations in genotype distribution of human sapoviruses and Aichi virus
      1 in wastewater in Southern Arizona, United States.
AB  - AIMS: To investigate the molecular epidemiology, especially temporal variations
      in genotype distribution, of sapoviruses and Aichi virus 1 (AiV-1) in Arizona,
      United States, by examining wastewater. METHODS AND RESULTS: A total of 26
      wastewater samples (13 influent and 13 effluent) were collected monthly from a
      wastewater treatment plant and viral strains were identified through nested
      reverse transcription-PCR followed by cloning and sequencing analysis. Identified
      sapovirus strains were classified into seven genotypes belonging to three
      genogroups (GI, GII, and GV): GI.1, GI.2, GI.3, GII.1, GII.2, GII.8 and GV.1,
      with a clear temporal shift. The majority of AiV-1 strains identified from the
      wastewater samples were classified into genotype B, and genotype A strains were
      identified in only two samples. CONCLUSIONS: We identified a number of sapovirus
      and AiV-1 strains belonging to multiple genotypes in wastewater samples collected
      over a 13-month period. Our results suggested a temporal shift in prevalent
      genotypes in the community. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the
      first study elucidating the genotype distribution of human sapoviruses and AiV-1
      in wastewater in the United States. Wastewater surveillance is especially useful
      for understanding molecular epidemiology of viruses that are less commonly tested
      in clinical diagnosis, including sapoviruses and AiV-1.

PMID- 29377503
TI  - Association between sociodemographic determinants and health outcomes in
      individuals with type 2 diabetes in Sweden.
AB  - BACKGROUND: Concurrent multifactorial treatment is needed to reduce consequent
      risks of diabetes, yet most studies investigating the relationship between
      sociodemographic factors and health outcomes have focused on only one risk factor
      at a time. Swedish health care is mainly tax-funded, thus providing an
      environment that should facilitate equal health outcomes in patients, independent
      of background, socioeconomic status, or health profile. This study aimed at
      investigating the association between several sociodemographic factors and
      diabetes-related health outcomes represented by HbA1c , systolic blood pressure,
      low-density lipoprotein cholesterol, predicted 5-year risk of cardiovascular
      disease, and statin use. METHODS: This large retrospective registry study was
      based on patient-level data from individuals diagnosed with type 2 diabetes
      during 2010 to 2011 (n = 416,228) in any of 7 Swedish regions (~65% of the
      Swedish population). Health equity in diabetes care analysed through multivariate
      regression analyses on intermediary outcomes (HbA1c , systolic blood pressure,
      and low-density lipoprotein), predicted 5-year risk of cardiovascular disease and
      process (i.e., statin use) after 1-year follow-up, adjusting for several
      sociodemographic factors. RESULTS: We observed differences in intermediary risk
      measures, predicted 5-year risk of cardiovascular disease, and process dependent
      on place of birth, sex, age, education, and social setting, despite Sweden's
      articulated vision of equal health care. CONCLUSIONS: Diabetes patients' health
      was associated with sociodemographic prerequisites. Furthermore, in addition to
      demographics (age and sex) and disease history, educational level, marital
      status, and region of birth are important factors to consider when benchmarking
      health outcomes, e.g., average HbA1c level, and evaluating the level of health
      equity between organizational units or between different administrative regions.

PMID- 29377504
TI  - A simple clinical model predicts incident hepatic steatosis in a community-based
      cohort: The Framingham Heart Study.
AB  - BACKGROUND AND AIMS: The factors associated with incident hepatic steatosis are
      not definitively known. We sought to determine factors associated with incident
      hepatic steatosis, as measured on computed tomography, in the community. METHODS:
      We studied Framingham Heart Study participants without heavy alcohol use or
      baseline hepatic steatosis who underwent computed tomography scans between 2002
      2005 (baseline) and 2008-2011 (follow-up). We performed a stepwise logistic
      regression procedure to determine the predictors associated with incident hepatic
      steatosis. RESULTS: We included 685 participants (mean age: 45.0 +/- 6.2 years,
      46.8% women). The incidence of hepatic steatosis in our sample was 17.1% over a
      mean 6.3 years of follow-up. Participants who developed hepatic steatosis had
      more adverse cardiometabolic profiles at baseline compared to those free of
      hepatic steatosis at follow-up. Multivariable stepwise regression analysis showed
      that a simple clinical model including age, sex, body mass index, alcohol
      consumption and triglycerides was predictive of incident hepatic steatosis (C
      statistic = 0.791, 95% CI: 0.748-0.834). A complex clinical model, which included
      visceral adipose tissue volume and liver phantom ratio added to the simple
      clinical model, and had improved discrimination for predicting incident hepatic
      steatosis (C statistic = 0.826, 95% CI: 0.786-0.866, P < .0001). CONCLUSIONS: The
      combination of demographic, clinical and imaging characteristics at baseline was
      predictive of incident hepatic steatosis. The use of our predictive model may
      help identify those at increased risk for developing hepatic steatosis who may
      benefit from risk factor modification although further investigation is
      warranted.

PMID- 29377506
TI  - CMV-infected kidney grafts drive the expansion of blood-borne CMV-specific T
      cells restricted by shared class I HLA molecules via presentation on donor cells.
AB  - We aimed to determine the role of cytomegalovirus (CMV)-infected donor cells in
      the development of a CMV-specific immune response in kidney transplant
      recipients. We assessed the CMV pp65-specific immune response by using interferon
      gamma ELISPOT and dextramers in peripheral blood mononuclear cells from 115
      recipients (D+R- 31, D+R + 44, D-R + 40) late after transplantation (mean 59 +/-
      42 months). Receiving a kidney from a D+ donor resulted in a higher number of IFN
      gamma-producing anti-CMV T cells (P = .004). This effect disappeared with the
      absence of shared HLA class I specificities between donors and recipients (P =
      .430). To confirm the role of donor cells in stimulating the expansion of newly
      developed CMV-specific CD8+ T cells after transplantation, we compared the number
      of HLA-A2-restricted CMV-specific CD8+ T cells in primo-infected recipients who
      received an HLA-A2 or non-HLA-A2 graft. The median of anti-CMV pp65 T cells
      restricted by HLA-A2 was very low for patients who received a non-HLA-A2 graft vs
      an HLA-A2 graft (300 [0-14638] vs. 17972 [222-85594] anti-CMV pp65 CD8+ T
      cells/million CD8+ T cells, P = .001). This adds new evidence that CMV-infected
      kidney donor cells present CMV peptides and drive an inflation of memory CMV
      specific CD8+ T cells, likely because of frequent CMV replications within the
      graft.

PMID- 29377505
TI  - Maternal diabetes up-regulates NOX2 and enhances myocardial ischaemia/reperfusion
      injury in adult offspring.
AB  - Offspring of diabetic mothers are at risk of cardiovascular diseases in
      adulthood. However, the underlying molecular mechanisms are not clear. We
      hypothesize that prenatal exposure to maternal diabetes up-regulates myocardial
      NOX2 expression and enhances ischaemia/reperfusion (I/R) injury in the adult
      offspring. Maternal diabetes was induced in C57BL/6 mice by streptozotocin.
      Glucose-tolerant adult offspring of diabetic mothers and normal controls were
      subjected to myocardial I/R injury. Vascular endothelial growth factor (VEGF)
      expression, ROS generation, myocardial apoptosis and infarct size were assessed.
      The VEGF-Akt (protein kinase B)-mammalian target of rapamycin (mTOR)-NOX2
      signalling pathway was also studied in cultured cardiomyocytes in response to
      high glucose level. In the hearts of adult offspring from diabetic mothers,
      increases were observed in VEGF expression, NOX2 protein levels and both Akt and
      mTOR phosphorylation levels as compared to the offspring of control mothers.
      After I/R, ROS generation, myocardial apoptosis and infarct size were all
      significantly higher in the offspring of diabetic mothers relative to offspring
      of control mothers, and these differences were diminished by in vivo treatment
      with the NADPH oxidase inhibitor apocynin. In cultured cardiomyocytes, high
      glucose increased mTOR phosphorylation, which was inhibited by the PI3 kinase
      inhibitor LY294002. Notably, high glucose-induced NOX2 protein expression and ROS
      production were inhibited by rapamycin. In conclusion, maternal diabetes promotes
      VEGF-Akt-mTOR-NOX2 signalling and enhances myocardial I/R injury in the adult
      offspring. Increased ROS production from NOX2 is a possible molecular mechanism
      responsible for developmental origins of cardiovascular disease in offspring of
      diabetic mothers.

PMID- 29377507
TI  - Palladium-Catalyzed Reductive Coupling Reaction of Terminal Alkynes with Aryl
      Iodides Utilizing Hafnocene Difluoride as a Hafnium Hydride Precursor Leading to
      trans-Alkenes.
AB  - Herein, we describe a reductive cross-coupling of alkynes and aryl iodides by
      using a novel catalytic system composed of a catalytic amount of palladium
      dichloride and a promoter precursor, hafnocene difluoride (Cp2 HfF2 ,
      Cp=cyclopentadienyl anion), in the presence of a mild reducing reagent, a
      hydrosilane, leading to a one-pot preparation of trans-alkenes. In this process,
      a series of coupling reactions efficiently proceeds through the following three
      steps: (i) an initial formation of hafnocene hydride from hafnocene difluoride
      and the hydrosilane, (ii) a subsequent hydrohafnation toward alkynes, and (iii) a
      final transmetalation of the alkenyl hafnium species to a palladium complex. This
      reductive coupling could be chemoselectively applied to the preparation of trans
      alkenes with various functional groups, such as an alkyl group, a halogen, an
      ester, a nitro group, a heterocycle, a boronic ester, and an internal alkyne.

PMID- 29377508
TI  - Clinical value of 18 FDG PET/CT in screening for distant metastases in head and
      neck squamous cell carcinoma.
AB  - OBJECTIVES: The detection of distant metastases is of major importance in
      management of head and neck squamous cell carcinoma patients. DESIGN: All
      patients underwent 18 FDG PET/CT for the detection of distant metastases.
      SETTING: Retrospective single-centre study. PARTICIPANTS: Head and neck squamous
      cell carcinoma patients with high-risk factors for distant metastases. MAIN
      OUTCOME MEASURES: Accuracy of 18 FDG PET/CT for the detection of distant
      metastases using clinical development of distant metastases and a minimal follow
      up of twelve months as reference standard. Comparison of overall survival between
      patients diagnosed with distant metastases during initial screening and patients
      diagnosed with distant metastases during follow-up. RESULTS: In 23 (12%) of the
      190 patients, 18 FDG PET/CT detected distant metastases at screening. Sensitivity
      and negative predictive value were 46.2% (95% CI 32.6-59.7) and 82.6% (95% CI
      76.8-88.5). No difference in median overall survival from the time of distant
      metastases detection was found between patients diagnosed with DM during work-up
      or during follow-up. CONCLUSIONS: In head and neck squamous cell carcinoma
      patients with high-risk factors, 18 FDG PET/CT has a high negative predictive
      value for the detection of distant metastases and should be used in daily
      clinical practice, although the sensitivity is limited when long-term follow-up
      is used as reference standard.

PMID- 29377509
TI  - Metal-Free and Alkali-Metal-Catalyzed Synthesis of Isoureas from Alcohols and
      Carbodiimides.
AB  - The first addition of alcohols to carbodiimides catalyzed by transition-metal
      free compounds employs 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and its alkali
      metal salts. Isoureas are obtained in short reaction times and high yields when
      TBDK is used as the catalyst. Control of the coordination sphere of potassium
      with exogenous chelating ligands, in combination with mechanistic DFT
      calculations, demonstrated the role and positive influence of the alkali-metal
      cation on the kinetics.

PMID- 29377510
TI  - BCAA Metabolism and Insulin Sensitivity - Dysregulated by Metabolic Status?
AB  - Branched-chain amino acids (BCAAs) appear to influence several synthetic and
      catabolic cellular signaling cascades leading to altered phenotypes in mammals.
      BCAAs are most notably known to increase protein synthesis through modulating
      protein translation, explaining their appeal to resistance and endurance athletes
      for muscle hypertrophy, expedited recovery, and preservation of lean body mass.
      In addition to anabolic effects, BCAAs may increase mitochondrial content in
      skeletal muscle and adipocytes, possibly enhancing oxidative capacity. However,
      elevated circulating BCAA levels have been correlated with severity of insulin
      resistance. It is hypothesized that elevated circulating BCAAs observed in
      insulin resistance may result from dysregulated BCAA degradation. This review
      summarizes original reports that investigated the ability of BCAAs to alter
      glucose uptake in consequential cell types and experimental models. The review
      also discusses the interplay of BCAAs with other metabolic factors, and the role
      of excess lipid (and possibly energy excess) in the dysregulation of BCAA
      catabolism. Lastly, this article provides a working hypothesis of the
      mechanism(s) by which lipids may contribute to altered BCAA catabolism, which
      often accompanies metabolic disease.

PMID- 29377511
TI  - Diabetes on demand and novel technologies.
AB  - To date, the use of technology for the management of diabetes represents a
      promising area of innovation that can dramatically change diabetics' lives. In
      the past decade, the use of diabetes devices has widely grown and looks to have
      partially improved diabetes management. The combination of cloud technology with
      real-expert intervention saves time and improves efficiency, as well as
      empowering the patient. The application of mathematical models applied to
      diabetes therapy could lead to significant improvement in life quality and
      challenge the burden of hypoglycaemia. Events where an individual needs support
      are instantly achieved, triggering outreach alerts via cloud and wireless
      connectivity, thereby improving patient compliance and reducing disease costs.

PMID- 29377512
TI  - Association of NRG1 and AUTS2 genetic polymorphisms with Hirschsprung disease in
      a South Chinese population.
AB  - Hirschsprung disease (HSCR) is a genetic disorder characterized by the absence of
      enteric ganglia. There are more than 15 genes identified as contributed to HSCR
      by family-based or population-based approaches. However, these findings were not
      fulfilled to explain the heritability of most sporadic cases. In this study,
      using 1470 HSCR and 1473 control subjects in South Chinese population, we
      replicated two variants in NRG1 (rs16879552, P = 1.05E-04 and rs7835688, P =
      1.19E-07), and further clarified the two replicated SNPs were more essential for
      patients with short-segment aganglionosis (SHSCR) (P = 2.37E-05). We also tried
      to replicate the most prominent signal (rs7785360) in AUTS2, which was a
      potential susceptibility gene with HSCR. In our results, in terms of individual
      association, marginal effect was observed to affect the HSCR patients following
      recessive model (P = 0.089). Noteworthy, significant intergenic synergistic
      effect between rs16879552 (NRG1) and rs7785360 (AUTS2) was identified through
      cross-validation by logistic regression (P = 2.45E-03, OR = 1.53) and multifactor
      dimensionality reduction (MDR, P < 0.0001, OR = 1.77). Significant correlation
      was observed between expression of these two genes in the normal segments of the
      colons (P = 0.018), together with differential expression of these genes between
      aganglionic colonic segments and normal colonic segments of the HSCR patients (P
      value for AUTS2 <0.0001, P value for NRG1 = 0.0243). Although functional
      evaluation is required, we supply new evidence for the NRG1 to HSCR and raised up
      a new susceptibility gene AUTS2 to a specific symptom for the disease.

PMID- 29377513
TI  - Unusual Cause of Peritonitis in Peritoneal Dialysis: Streptococcus vestibularis.

PMID- 29377514
TI  - Hypothesis: apo-lactoferrin-Galantamine Proteo-alkaloid Conjugate for Alzheimer's
      disease Intervention.
AB  - Alzheimer's disease (AD) is known to be caused by the accumulation of deformed
      beta amyloid and hyperphosphorylated tau proteins resulting into formation and
      aggregation of senile plaques and neurofibrillary tangles in the brain.
      Additionally, AD is associated with the accumulation of iron or metal ions in the
      brain which causes oxidative stress. Galantamine (Gal) is one of the therapeutic
      agents that has been approved for the treatment of AD, but still saddled with
      numerous side effects and could not address the issue of iron accumulation in the
      brain. The use of metal chelators to address the iron accumulation has not been
      successful due to toxicity and inability to address the aggregation of the
      plaques. We therefore hypothesize a combinatorial antioxidant-metal-chelator
      approach by formulating a single dosage form that has the ability to prevent the
      formation of free radicals, plaques and accumulation of iron in the brain. This
      can be achieved by conjugating Gal with apo-lactoferrin (ApoLf), a natural
      compound that has high binding affinity for iron, to form an apo-lactoferrin
      galantamine proteo-alkaloid conjugate (ApoLf-Gal) as a single dosage form for AD
      management. The conjugation is achieved through self-assembly of ApoLf which
      results in encapsulation of Gal. ApoLf changes its conformational structure in
      the presence of iron; therefore, ApoLf-Gal is proposed to deliver Gal and pick up
      excess iron when in contact with iron. This strategy has the potential to proffer
      a dual neuroprotection and neurotherapeutic interventions for the management of
      AD.

PMID- 29377516
TI  - Bacterial Surface Traits Influence Digestion by Tetrahymena pyriformis and Alter
      Opportunity to Escape from Food Vacuoles.
AB  - Endosymbiotic interactions are frequently found in nature, especially in the
      group of protists. Even though many endosymbioses have been studied in detail,
      little is known about the mechanistic origins and physiological prerequisites of
      endosymbiont establishment. A logical step towards the development of
      endocytobiotic associations is evading digestion and escaping from the host's
      food vacuoles. Surface properties of bacteria are probably involved in these
      processes. Therefore, we chemically modified the surface of a transformant strain
      of Escherichia coli prior to feeding to Tetrahymena pyriformis. N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide allows any substance carrying amino- or
      carboxyl groups to be bound covalently to the bacterial surface by forming a
      peptide bond, thus, altering its properties biochemically and biophysically in a
      predictable manner. The effect of different traits on digestion of T. pyriformis
      was examined by fluorescence and transmission electron microscopy. The efficiency
      of digestion differs considerably depending on the coupled substances. Alkaline
      substances inhibit digestion partially, resulting in incomplete digestion and
      slightly enhanced escape rates. Increasing hydrophobicity leads to much higher
      escape frequencies. Both results point to possible mechanisms employed by
      pathogenic bacteria or potential endosymbionts in evading digestion and
      transmission to the host's cytoplasm.

PMID- 29377517
TI  - Inoculation history affects community composition in experimental freshwater
      bacterioplankton communities.
AB  - Priority effects occur when the arrival order of species or genotypes has a
      lasting effect on community or population structure. For freshwater bacteria,
      priority effects have been shown experimentally among individual species, but no
      experiments have been performed using complex natural communities. We
      investigated experimentally whether a foreign bacterioplankton community
      influences the community assembly trajectory when inoculated prior to the local
      community, whether inoculation time lag affects priority effects, and how the
      individual OTUs responded to time lag. Two bacterioplankton communities from
      dissimilar ponds were inoculated into one of the natural media with a time lag of
      0, 12, 36 or 60 h, giving advantage in time to the foreign community. All three
      time lags resulted in priority effects, as the final community composition of
      these treatments differed significantly from that of the treatment with no time
      lag, but compositional shifts were not linear to inoculation time lag. The
      responses of individual OTUs to time lag were highly diverse and not predictable
      based on their immigration history or relative abundance in the inocula or
      control. The observed impact and complexity of priority effects in multispecies
      systems emphasize the importance of this process in structuring both natural and
      industrial bacterial communities.

PMID- 29377518
TI  - Site-Selective Functionalization of Flagellin by Steric Self-Protection: A
      Strategy To Facilitate Flagellin as a Self-Adjuvanting Carrier in Conjugate
      Vaccine.
AB  - Flagellin (FliC) can act as a carrier protein in the preparation of conjugate
      vaccines to elicit a T-cell-dependent immune response and as an intrinsic
      adjuvant to activate the toll-like receptor 5 (TLR5) to enhance vaccine potency.
      To enable the use of FliC as a self-adjuvanting carrier, an effective method for
      site-selective modification (SSM) of pertinent amino-acid residues in the D2 and
      D3 domains of FliC is explored without excessive modification of the D0 and D1
      domains, which are responsible for activating and binding with TLR5. In highly
      concentrated Na2 SO4 solution, FliC monomers form flagellar filaments, in which
      the D0 and D1 domains are situated inside the tubular structure. Thus, the lysine
      residues (K219, K224, K324, and K331) in the D2 and D3 domains of flagellin are
      selectively modified by a diazo-transfer reaction with imidazole-1-sulfonyl
      azide. The sites with azido modification are confirmed by MALDI-TOF-MS, ESI-TOF
      MS, and LC-MS/MS analyses along with label-free quantitation. The azido-modified
      filament dissolves to give FliC monomers, which can conjugate with alkyne-hinged
      saccharides by the click reaction. Transmission electron microscopy imaging,
      dynamic light scattering measurements, and the secreted embryonic alkaline
      phosphatase reporter assay indicate that the modified FliC monomers retain the
      ability either to bind with TLR5 or to reassemble into filaments. Overall, this
      study establishes a feasible method for the SSM of FliC by steric self-protection
      of the D0 and D1 domains.

PMID- 29377515
TI  - Impact of interferon-free regimens on the glomerular filtration rate during
      treatment of chronic hepatitis C in a real-life cohort.
AB  - Little data are available on renal toxicity exerted by direct-acting antivirals
      (DAAs) in real life. The aim of this study was to assess the impact of direct
      acting antivirals against hepatitis C virus infection currently used in Spain and
      Portugal on the estimated glomerular filtration rate (eGFR) in clinical practise.
      From an international, prospective multicohort study, patients treated with DAAs
      for at least 12 weeks and with eGFR >=30 mL/min per 1.73 m2 at baseline were
      selected. eGFR was determined using the CKD-EPI formula. A total of 1131 patients
      were included; 658 (58%) were HIV/HCV-coinfected patients. Among the 901 patients
      treated for 12 weeks, median (interquartile range) eGFR was 100 (87-107) at
      baseline vs 97 (85-105) mL/min per 1.73 m2 at week 12 of follow-up (FU12) post
      treatment (P < .001). For HIV-coinfected subjects who received tenofovir plus a
      ritonavir-boosted HIV protease inhibitor (PI/r), baseline vs FU12 eGFR were 104
      (86-109) vs 104 (91-110) mL/min per 1.73 m2 (P = .913). Among subjects receiving
      ombitasvir/paritaprevir with or without dasabuvir, eGFR did not show any
      significant change. Of 1100 subjects with eGFR >60 mL/min per 1.73 m2 at
      baseline, 22 (2%) had eGFR <60 mL/min per 1.73 m2 at FU12, but none presented
      with eGFR <30 mL/min per 1.73 m2 . In conclusion, eGFR slightly declines during
      therapy with all-oral DAAs and this effect persists up to 12 weeks after stopping
      treatment in subjects with normal to moderately impaired renal function,
      regardless of HIV status. Concomitant use of tenofovir plus PI/r does not seem to
      have an impact on eGFR.

PMID- 29377519
TI  - Nurses' competence in genetics: An integrative review.
AB  - The aim of this integrative review was to update a mixed method systematic review
      by Skirton, O'Connor, and Humphreys (2012) that reported on nurses' levels of
      competence in using genetics in clinical practice. Three electronic databases
      were searched using selected key words. Research studies published in English
      between January 2011 and September 2017 reporting levels of nurse competence in
      genetics or genomics were eligible for inclusion. The selected studies were
      subjected to thematic analysis. Three main themes were identified: (i) genomic
      knowledge and utilization, (ii) perceived relevance to practice, and (iii)
      genomic education. While the reviewed papers produced varied findings, many
      nurses were shown to have poor genomic knowledge and/or competency, and yet there
      was a consensus that most nurses believe genomics is important to their practice.
      The present review indicated that in the past 5 years nurses have made minimal
      progress toward achieving the core genomic competencies appropriate for clinical
      practice.

PMID- 29377520
TI  - Comparative Pharmacological Study of Common NMDA Receptor Open Channel Blockers
      Regarding Their Affinity and Functional Activity toward GluN2A and GluN2B NMDA
      Receptors.
AB  - Because only a few studies have investigated the affinity and functional activity
      of NMDA receptor open channel blockers under the same assay conditions, a
      comparative study of common open channel blockers is of major interest. The
      pharmacological activities of MK-801, phencyclidine (PCP), dexoxadrol, etoxadrol,
      (S)- and (R)-ketamine, dextromethorphan, memantine, and amantadine were analyzed
      under uniform assay conditions. Affinity toward the PCP and ifenprodil binding
      sites was recorded in radioligand binding assays. GluN2A and GluN2B subtype
      specific cytoprotective activity was determined in lactate dehydrogenase (LDH)
      assays. The data were correlated with published IC50 values obtained in two
      electrode voltage clamp experiments. A high correlation was found between PCP
      affinity, ion flux inhibition, and cytoprotective activity. The channel blockers
      were classified into four groups showing high, moderate, low, and very low
      potency. Some of the open channel blockers display unexpected subtype
      selectivity. The comparative study allows the characterization of open channel
      blockers from their receptor ligand interaction via inhibition of ion flux up to
      overall cytoprotective activity. The subtype preference of some open channel
      blockers will stimulate the development of novel subtype-selective open channel
      blockers with decreased side effect potential.

PMID- 29377521
TI  - Subsequent Unintended Pregnancy Among US Women Who Receive or Are Denied a Wanted
      Abortion.
AB  - INTRODUCTION: Seventeen percent of women in the United States experience more
      than one unintended pregnancy in their lifetimes. However, few studies examine
      how the resolution of unintended pregnancy, whether in birth or abortion, affects
      the likelihood of a subsequent unintended pregnancy. Our objective was to
      determine whether receiving or being denied a wanted abortion is associated with
      subsequent unintended pregnancy. METHODS: The Turnaway Study, a 5-year,
      prospective cohort study, followed women who sought an abortion at one of 30
      abortion facilities across the United States between 2008 and 2010. Secondary
      analysis of the Turnaway data analyzed the effects of various factors on time to
      subsequent unintended pregnancy. RESULTS: By 5 years, the rate of unintended
      pregnancy was 42 per 100 women with no difference between those who received and
      those who were denied a wanted abortion. Women aged 35 to 46 years (vs those aged
      20-24 years), women with a college degree (vs women who had completed high school
      or obtained a general education diploma), and foreign-born (vs native-born) women
      had a reduced rate of a subsequent unplanned pregnancy (adjusted hazard ratio
      [AHR], 0.30; 95% confidence interval [CI], 0.16-0.57; AHR, 0.54, 95% CI, 0.30
      0.97; AHR, 0.44; 95% CI, 0.25-0.77, respectively). Higher parity and a history of
      depression were positively associated with a higher rate of subsequent unintended
      pregnancy. There was no difference in the outcomes of these unintended
      pregnancies by study group; approximately one-sixth ended in miscarriage and one
      quarter of subsequent unintended pregnancies ended in abortion. DISCUSSION:
      Neither receiving nor being denied abortion is associated with subsequent
      unintended pregnancy risk. Other factors such as nativity, parity, age, and
      mental health history are associated with multiple unintended pregnancies.
      Ensuring access to abortion services will not increase the likelihood that women
      will experience subsequent unintended pregnancies.

PMID- 29377522
TI  - Dulaglutide treatment results in effective glycaemic control in latent autoimmune
      diabetes in adults (LADA): A post-hoc analysis of the AWARD-2, -4 and -5 Trials.
AB  - AIMS: Patients with a type-2-diabetes (T2D) phenotype positive for glutamic acid
      decarboxylase antibodies (GADA) represent the majority of cases of latent
      autoimmune diabetes of the adult (LADA). The GLP-1 receptor agonist dulaglutide,
      recently introduced for treatment of T2D, has yet to be evaluated in LADA
      patients. Our primary objective was to evaluate the effect of dulaglutide on
      glycaemic control (HbA1c) in GADA-positive LADA vs GADA-negative T2D patients.
      METHODS: A post-hoc analysis was performed using data from 3 randomized phase 3
      trials (AWARD-2,-4,-5; patients with GADA assessment) which were part of the
      dulaglutide clinical development programme in T2D. LADA patients were identified
      by GADA >=5 IU/mL (ELISA). Changes in HbA1c during 12 months of treatment with
      dulaglutide or comparator were analysed using mixed-effect model repeated
      measures. RESULTS: Of 2466 adults tested for GADA (dulaglutide, 1710; glargine,
      298; sitagliptin, 294; placebo, 164), 2278 (92.4%) were GADA-negative and 188
      (7.6%) were GADA-positive, including 58 GADA-high patients (> 200 IU/mL) and 130
      GADA-low patients (<=200 and >=5 IU/mL). Overall, baseline parameters were
      comparable between the groups. Dulaglutide resulted in comparable HbA1c
      reductions in GADA-negative (LS mean change [95%CI], -1.09% [-1.15, -1.03]) and
      GADA-positive patients (-0.94% [-1.15, -0.72]) at 12 months. HbA1c reductions
      were numerically, but not statistically, significantly larger in GADA-low
      patients (-1.02% [-1.26, -0.78]) vs GADA-high patients (-0.72% [-1.21,-0.24]) at
      12 months. Similar outcomes were observed at 3 and 6 months. CONCLUSIONS: These
      data are the first to indicate that dulaglutide was effective in reducing HbA1c
      in LADA patients.

PMID- 29377523
TI  - Electrochemical Dynamics of a Single Platinum Nanoparticle Collision Event for
      the Hydrogen Evolution Reaction.
AB  - Chronoamperometry was used to study the dynamics of Pt nanoparticle (NP)
      collision with an inert ultramicroelectrode via electrocatalytic amplification
      (ECA) in the hydrogen evolution reaction. ECA and dynamic light scattering (DLS)
      results reveal that the NP colloid remains stable only at low proton
      concentrations (1.0 mm) under a helium (He) atmosphere, ensuring that the
      collision events occur at genuinely single NP level. Amperometry of single NP
      collisions under a He atmosphere shows that each discrete current profile of the
      collision event evolves from spike to staircase at more negative potentials,
      while a staircase response is observed at all of the applied potentials under
      hydrogen-containing atmospheres. The particle size distribution estimated from
      the diffusion-controlled current in He agrees well with electron microscopy and
      DLS observations. These results shed light on the interfacial dynamics of the
      single nanoparticle collision electrochemistry.

PMID- 29377525
TI  - Mesoporous bioactive glass embedding propolis and cranberry antibiofilm
      compounds.
AB  - The aim of this study was to evaluate the chemical reactivity of 58S mesoporous
      bioactive glass (MBG) particles in as-synthesized condition and after embedding
      propolis and cranberry antibiofilm compounds at different concentrations. MBG 58S
      was synthesized by alkali sol-gel method with the addition of the triblock
      pluronic copolymer P123 as surfactant. Samples were characterized by
      physicochemical properties measurement, N2 adsorption/desorption analysis, and
      field emission gun scanning electron microscopy (FEGSEM) observations. MBG
      powders were immersed into 5 and 10 ug/mL propolis or cranberry solutions for 24
      h. The chemical reactivity of the specimens was evaluated by FEGSEM, EDX, FTIR,
      Ca/P ratio, XRD, and sample weight gain analysis after being immersed in
      simulated body fluid (SBF) for 8, 24, and 72 h. MBG particles exhibited the
      expected chemical composition with a particle size distribution ranging from 1.44
      to 955 um, and a mean particle size of 154 um. MBG particles exhibited a pore
      volume of 0.8 cc/g, pore radius of ~2 nm, and surface area of 350.2 m2 /g,
      according to BJH and BET analyses. A hydroxyl-carbonate apatite (HCAp) layer was
      formed on all samples after SBF immersion for 72 h. Pure MBG showed the highest
      chemical reactivity after 72 h, with the resulting apatite layer exhibiting a
      Ca/P ratio of ~1.6 in accordance to stoichiometric biological apatite. MBG
      embedding propolis and cranberry can be considered for future microbiological
      analysis since the presence of propolis or cranberry did not interfere with MBG's
      ability to develop a HCAp layer, which is an essential feature for bone
      regeneration applications. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A: 1614-1625, 2018.

PMID- 29377524
TI  - Model-driven design of a minimal medium for Akkermansia muciniphila confirms
      mucus adaptation.
AB  - The abundance of the human intestinal symbiont Akkermansia muciniphila has found
      to be inversely correlated with several diseases, including metabolic syndrome
      and obesity. A. muciniphila is known to use mucin as sole carbon and nitrogen
      source. To study the physiology and the potential for therapeutic applications of
      this bacterium, we designed a defined minimal medium. The composition of the
      medium was based on the genome-scale metabolic model of A. muciniphila and the
      composition of mucin. Our results indicate that A. muciniphila does not code for
      GlmS, the enzyme that mediates the conversion of fructose-6-phosphate (Fru6P) to
      glucosamine-6-phosphate (GlcN6P), which is essential in peptidoglycan formation.
      The only annotated enzyme that could mediate this conversion is Amuc-NagB on
      locus Amuc_1822. We found that Amuc-NagB was unable to form GlcN6P from Fru6P at
      physiological conditions, while it efficiently catalyzed the reverse reaction. To
      overcome this inability, N-acetylglucosamine needs to be present in the medium
      for A. muciniphila growth. With these findings, the genome-scale metabolic model
      was updated and used to accurately predict growth of A. muciniphila on synthetic
      media. The finding that A. muciniphila has a necessity for GlcNAc, which is
      present in mucin further prompts the adaptation to its mucosal niche.

PMID- 29377526
TI  - Low maternal vitamin D status in pregnancy increases the risk of childhood
      obesity.
AB  - BACKGROUND: Vitamin D may modulate adipogenesis. However, limited studies have
      investigated the effect of maternal vitamin D during pregnancy on offspring
      adiposity or cardiometabolic parameters with inconclusive results. OBJECTIVES:
      The objective of this study is to examine the association of maternal 25(OH)
      vitamin D [25(OH)D] status with offspring obesity and cardiometabolic
      characteristics in 532 mother-child pairs from the prospective pregnancy cohort
      Rhea in Crete, Greece. METHODS: Maternal 25(OH)D concentrations were measured at
      the first prenatal visit (mean: 14 weeks, SD: 4). Child outcomes included body
      mass index standard deviation score, waist circumference, skin-fold thickness,
      blood pressure and serum lipids at ages 4 and 6 years. Body fat percentage was
      also measured at 6 years. Body mass index growth trajectories from birth to 6
      years were estimated by mixed effects models with fractional polynomials of age.
      Adjusted associations were obtained via multivariable linear regression analyses.
      RESULTS: About two-thirds of participating mothers had 25(OH)D concentrations <50
      nmol L-1 . Offspring of women in the low 25(OH)D tertile (<37.7 nmol L-1 ) had
      higher body mass index standard deviation score (beta 0.20, 95% CI: 0.03, 0.37),
      and waist circumference (beta 0.87 95% CI: 0.12, 1.63) at preschool age, compared
      with the offspring of women with higher 25(OH)D measurements (>=37.7 nmol L-1 ),
      on covariate-adjusted analyses. The observed relationships persisted at age 6
      years. We found no association between maternal 25(OH)D concentrations and
      offspring blood pressure or serum lipids at both time points. CONCLUSIONS:
      Exposure to very low 25(OH)D concentrations in utero may increase childhood
      adiposity indices. Given that vitamin D is a modifiable risk factor, our findings
      may have important public health implications.

PMID- 29377527
TI  - Improvement in the Photobiological Hydrogen Production of Aggregated Chlorella by
      Dimethyl Sulfoxide.
AB  - Photobiological hydrogen production plays a vital role in generating clean
      renewable energy owing to its low energy consumption and environmental
      friendliness. Although materials-induced Chlorella aggregates have been developed
      to achieve sustained photobiological hydrogen production under normal aerobic
      conditions, the yield is relatively low and equals only 0.42 % of the light-to-H2
      energy-conversion efficiency. Herein, we report that only 0.5 vol % dimethyl
      sulfoxide in an aqueous environment significantly enhances the H2 yield produced
      by aggregated Chlorella, reaching 0.69 % of the light-to-H2 energy-conversion
      efficiency. This improvement can be attributed to an increase in the cellular
      respiration rate by dimethyl sulfoxide, which results in a decrease in the oxygen
      content inside the aggregates and, ultimately, to the activation of more
      hydrogenases. More generally, this strategy consists of a functional enhancement
      in organism-material hybrids by using small molecules.

PMID- 29377529
TI  - One-Way Particle Transport Using Oscillatory Flow in Asymmetric Traps.
AB  - One challenge of integrating of passive, microparticles manipulation techniques
      into multifunctional microfluidic devices is coupling the continuous-flow format
      of most systems with the often batch-type operation of particle separation
      systems. Here, a passive fluidic technique-one-way particle transport-that can
      conduct microparticle operations in a closed fluidic circuit is presented.
      Exploiting pass/capture interactions between microparticles and asymmetric traps,
      this technique accomplishes a net displacement of particles in an oscillatory
      flow field. One-way particle transport is achieved through four kinds of trap
      particle interactions: mechanical capture of the particle, asymmetric
      interactions between the trap and the particle, physical collision of the
      particle with an obstacle, and lateral shift of the particle into a particle
      trapping stream. The critical dimensions for those four conditions are found by
      numerically solving analytical mass balance equations formulated using the
      characteristics of the flow field in periodic obstacle arrays. Visual observation
      of experimental trap-particle dynamics in low Reynolds number flow (<0.01)
      confirms the validity of the theoretical predictions. This technique can
      transport hundreds of microparticles across trap rows in only a few fluid
      oscillations (<500 ms per oscillation) and separate particles by their size
      differences.

PMID- 29377530
TI  - A mixed methods analysis of experiences and expectations among early-career
      medical oncologists in Australia.
AB  - AIM: A viable and sustainable medical oncology profession is integral for meeting
      the increasing demand for quality cancer care. The aim of this study was to
      explore the workforce-related experiences, perceptions and career expectations of
      early-career medical oncologists in Australia. METHODS: A mixed-methods design,
      including a survey (n  =  170) and nested qualitative semistructured interviews
      (n  =  14) with early-career medical oncologists. Recruitment was through the
      Medical Oncology Group of Australia. Qualitative data were thematically analyzed
      and for the survey results, logistic regression modeling was conducted. RESULTS:
      Early-career medical oncologists experienced uncertainty regarding their future
      employment opportunities. The competitive job market has made them cautious about
      securing a preferred job leading to a perceived need to improve their
      qualifications through higher degree training and research activities. The
      following themes and trends were identified from the qualitative and quantitative
      analyses: age, career stage and associated early-career uncertainty; locale,
      professional competition and training preferences; participation in research and
      evolving professional expectations; and workload and career development
      opportunities as linked to career uncertainty. CONCLUSION: Perceived diminished
      employment opportunities in the medical oncology profession, and shifting
      expectations to be "more qualified," have increased uncertainty among junior
      medical oncologists in terms of their future career prospects. Structural factors
      relating to adequate funding of medical oncology positions may facilitate or
      inhibit progressive change in the workforce and its sustainability. Workforce
      planning and strategies informed by findings from this study will be necessary in
      ensuring that both the needs of cancer patients and of medical oncologists are
      met.

PMID- 29377528
TI  - Filifactor alocis modulates human neutrophil antimicrobial functional responses.
AB  - Filifactor alocis is a newly appreciated pathogen in periodontal diseases.
      Neutrophils are the predominant innate immune cell in the gingival crevice. In
      this study, we examined modulation of human neutrophil antimicrobial functions by
      F. alocis. Both non-opsonised and serum-opsonised F. alocis were engulfed by
      neutrophils but were not efficiently eliminated. Challenge of neutrophils with
      either non-opsonised or serum-opsonised F. alocis induced a minimal intracellular
      as well as extracellular respiratory burst response compared to opsonised
      Staphylococcus aureus and fMLF, respectively. However, pretreatment or
      simultaneous challenge of neutrophils with F. alocis did not affect the
      subsequent oxidative response to a particulate stimulus, suggesting that the
      inability to trigger the respiratory response was only localised to F. alocis
      phagosomes. In addition, although neutrophils engulfed live or heat-killed F.
      alocis with the same efficiency, heat-killed F. alocis elicited a higher
      intracellular respiratory burst response compared to viable organisms, along with
      decreased surface expression of CD35, a marker of secretory vesicles. F. alocis
      phagosomes remained immature by delayed and reduced recruitment of specific and
      azurophil granules, respectively. These results suggest that F. alocis withstands
      neutrophil antimicrobial responses by preventing intracellular ROS production,
      along with specific and azurophil granule recruitment to the bacterial phagosome.

PMID- 29377531
TI  - Ultrasmall Pb:Ag2 S Quantum Dots with Uniform Particle Size and Bright Tunable
      Fluorescence in the NIR-II Window.
AB  - Ag2 S quantum dots (QDs) are well-known near-infrared fluorophores and have
      attracted great interest in biomedical labeling and imaging in the past years.
      However, their photoluminescence efficiency is hard to compete with Cd-, Pb-based
      QDs. The high Ag+ mobility in Ag2 S crystal, which causes plenty of cation
      deficiency and crystal defects, may be responsible mainly for the low
      photoluminescence quantum yield (PLQY) of Ag2 S QDs. Herein, a cation-doping
      strategy is presented via introducing a certain dosage of transition metal Pb2+
      ions into Ag2 S nanocrystals to mitigate this intrinsic shortcoming. The Pb-doped
      Ag2 S QDs (designated as Pb:Ag2 S QDs) present a renovated crystal structure and
      significantly enhanced optical performance. Moreover, by simply adjusting the
      levels of Pb doping in the doped nanocrystals, Pb:Ag2 S QDs with bright emission
      (PLQY up to 30.2%) from 975 to 1242 nm can be prepared without altering the
      ultrasmall particle size (~2.7-2.8 nm). Evidently, this cation-doping strategy
      facilitates both the renovation of crystal structure of Ag2 S QDs and modulation
      of their optical properties.

PMID- 29377532
TI  - To reduce maternal mortality, we must know and respond to women's personal
      stories.

PMID- 29377533
TI  - Microtensile bond strength of universal adhesives to flat versus Class I cavity
      dentin with pulpal pressure simulation.
AB  - OBJECTIVES: The aim of this study was to test long-term microtensile bond
      strength (uTBS) of 2 universal adhesives applied to dentin following "total-etch"
      (TE) or "self-etch" (SE) protocols and aged by direct or indirect water exposure
      using simulated pulpal pressure. MATERIALS AND METHODS: Single Bond Universal
      (SBU, 3M ESPE) or Ipera Bond (IP, Itena) were applied to mid-coronal dentin
      ("flat dentin") or Class I cavity ("cavity dentin") following TE or SE protocols
      in 112 extracted human third molars. Sixteen groups (n = 7 per group) were
      prepared, 8 groups for uTBS measurements after 24 hours, and further 8 groups for
      measurements after 6 months storage. "Cavity dentin" groups were subjected to
      simulated hydrostatic pulpal pressure of 15 cm H2 O using a custom-made device
      before cutting 1 * 1 mm sticks while "flat dentin" groups were cut into sticks
      and directly exposed to deionized water. RESULTS: Generally, the TE protocol
      resulted in highest uTBS values on flat dentin initially for both adhesives
      (general linear model, P < .05). Long-term storage resulted in significantly
      lower uTBS values for the TE protocol (P < .05) while the SE protocol showed
      comparable values after 6 months (P > .05). "Cavity dentin" with simulated pulpal
      pressure resulted in lower uTBS than "flat dentin" (P < .05). For both adhesives,
      uTBS was in the range of 19-42 MPa initially and 16-36 MPa after 6 months
      storage. CONCLUSIONS: uTBS to dentin of universal adhesives is more stable in the
      long term following the SE than TE protocol. Simulated pulpal pressure and cavity
      type sample preparation may be recommended for uTBS testing as a more clinically
      relevant strategy. CLINICAL SIGNIFICANCE: Microtensile bond strength to dentin of
      universal adhesives appears more stable following the "self-etch" than "total
      etch" protocol after long-term degradation. More clinically relevant data may be
      obtained using simulated pulpal pressure and cavity-type sample preparation in
      the study design.

PMID- 29377534
TI  - The Five Attributes of a Supportive Midwifery Practice Climate: A Review of the
      Literature.
AB  - INTRODUCTION: A supportive work climate is associated with decreased burnout and
      attrition, and increased job satisfaction and employee health. A review of the
      literature was conducted in order to determine the unique attributes of a
      supportive practice climate for midwives. METHODS: The midwifery literature was
      reviewed and synthesized using concept analysis technique guided by literature
      from related professions. The search was conducted primarily in PubMed, CINAHL,
      Web of Science, and Google Scholar. Articles were included if they were conducted
      between 2006 and 2016 and addressed perceptions of the midwifery practice climate
      as it related to patient, provider, and organizational outcomes. RESULTS: The
      literature identified 5 attributes consistent with a supportive midwifery
      practice climate: effective leadership, adequate resources, collaboration,
      control of one's work, and support of the midwifery model of care. Effective
      leadership styles include situational and transformational, and 9 traits of
      effective leaders are specified. Resources consist of time, personnel, supplies,
      and equipment. Collaboration encompasses relationships with all members of the
      health care team, including midwives inside and outside of one's practice.
      Additionally, the patients are considered collaborating members of the team.
      Characteristics of effective collaboration include a shared vision, role clarity,
      and respectful communication. Support for the midwifery model of care includes
      value congruence, developing relationships with women, and providing high-quality
      care. DISCUSSION: The attributes of a supportive midwifery practice climate are
      generally consistent with theoretical models of supportive practice climates of
      advanced practice nurses and physicians, with the exception of a more inclusive
      definition of collaboration and support of the midwifery model of care. The
      proposed Midwifery Practice Climate Model can guide instrument development,
      determining relationships between the attributes of the practice climate and
      outcomes, and creating interventions to improve the practice climate, workforce
      stability, and patient outcomes.

PMID- 29377535
TI  - Hot Water Generates Crystalline Organic Materials.
AB  - In hot water: Hydrothermal crystallization was recently used to transform
      amporphous polymer networks into amide-linked, stable covalent-organic
      frameworks. This work is highlighted in the context of the synthesis and
      especially crystallization of organic materials by using high-temperature water.

PMID- 29377536
TI  - Recent Advances in Supramolecular Gels and Catalysis.
AB  - Over the past two decades, supramolecular gels have attracted significant
      attention from scientists in diverse research fields and have been extensively
      developed. This review mainly focuses on the significant achievements in
      supramolecular gels and catalysis. First, by incorporating diverse catalytic
      sites and active organic functional groups into gelator molecules, supramolecular
      gels have been considered as a novel matrix for catalysis. In addition, these
      rationally designed supramolecular gels also provide a variety of templates to
      access metal nanocomposites, which may function as catalysts and exhibit high
      activity in diverse catalytic transformations. Finally, as a new kind of
      biomaterial, supramolecular gels formed in situ by self-assembly triggered by
      catalytic transformations are also covered herein.

PMID- 29377537
TI  - Counterpoint to the hypothesis that SGLT2 inhibitors protect the heart by
      antagonizing leptin.

PMID- 29377538
TI  - The Effect of Voltage Charging on the Transport Properties of Gold Nanotube
      Membranes.
AB  - Porous membranes are used in chemical separations and in many electrochemical
      processes and devices. Research on the transport properties of a unique class of
      porous membranes that contain monodisperse gold nanotubes traversing the entire
      membrane thickness is reviewed here. These gold nanotubes can act as conduits for
      ionic and molecular transports through the membrane. Because the tubes are
      electronically conductive, they can be electrochemically charged by applying a
      voltage to the membrane. How this "voltage charging" affects the transport
      properties of gold nanotube membranes is the subject of this Review. Experiments
      showing that voltage charging can be used to reversibly switch the membrane
      between ideally cation- and anion-transporting states are reviewed. Voltage
      charging can also be used to enhance the ionic conductivity of gold nanotube
      membranes. Finally, voltage charging to accomplish electroporation of living
      bacteria as they pass through gold nanotube membranes is reviewed.

PMID- 29377539
TI  - Therapeutic effects of a recombinant human collagen peptide bioscaffold with
      human adipose-derived stem cells on impaired wound healing after radiotherapy.
AB  - Chronic changes following radiotherapy include alterations in tissue-resident
      stem cells and vasculatures, which can lead to impaired wound healing. In this
      study, novel recombinant human collagen peptide (rhCP) scaffolds were evaluated
      as a biomaterial carrier for cellular regenerative therapy. Human adipose-derived
      stem cells (hASCs) were successfully cultured on rhCP scaffolds. By hASC culture
      on rhCP, microarray assay indicated that expression of genes related to cell
      proliferation and extracellular matrix production was upregulated. Pathway
      analyses revealed that signaling pathways related to inflammatory suppression and
      cell growth promotion were activated as well as signaling pathways consistent
      with some growth factors including vascular endothelial growth factor, hepatocyte
      growth factor, and transforming growth factor beta, although gene expression of
      these growth factors was not upregulated. These findings suggest the rhCP
      scaffold showed similar biological actions to cytokines regulating cell growth
      and immunity. In subsequent impaired wound healing experiments using a locally
      irradiated (20 Gray) mouse, wound treatment with rhCP sponges combined with
      cultured hASCs and human umbilical vein endothelial cells accelerated wound
      closure compared with wounds treated with rhCP with hASCs alone, rhCP only, and
      control (dressing alone), with better healing observed according to this order.
      These results indicating the therapeutic value of rhCP scaffolds as a topical
      biomaterial dressing and a biocarrier of stem cells and vascular endothelial
      cells for regenerating therapies. The combination of rhCP and functional cells
      was suggested to be a potential tool for revitalizing stem cell-depleted
      conditions such as radiation tissue damage.

PMID- 29377540
TI  - MicroRNA-99a is a novel regulator of KDM6B-mediated osteogenic differentiation of
      BMSCs.
AB  - Skeletal tissue originates from mesenchymal stem cells (MSCs) with
      differentiation potential into the osteoblast lineage regulated by essential
      transcriptional and post-transcriptional mechanisms. Recently, miRNAs and histone
      modifications have been identified as novel key regulators of osteogenic
      differentiation of MSCs. Here, we identified miR-99a and its target lysine (K)
      specific demethylase 6B (KDM6B) gene as novel modulators of osteogenic
      differentiation of bone mesenchymal stem cells (BMSCs). Microarray profiling and
      further validation by quantitative real-time RT-PCR revealed that miR-99a was up
      regulated during osteoblastic differentiation of BMSCs, and decreased in
      differentiated osteoblasts. Transfection of miR-99a mimics inhibited osteoblastic
      commitment and differentiation of BMSCs, whereas inhibition of miR-99a by
      inhibitors enhances these processes. KDM6B was determined as one of important
      targets of miR-99a, which was further confirmed by luciferase assay of 3'-UTR of
      KDM6B. Moreover, HOX gene level decreased after transfection of miR-99a mimics in
      BMSCs, which indicated that KDM6B is a bona fide target of miR-99a. Furthermore,
      in a model of in vivo bone regeneration, osteoblast-specific gain- and loss-of
      function experiments performed using cranial bone defects revealed that miR-99a
      mimics-transfected BMSCs reduced bone formation, and conversely, miR-99a
      inhibitors-transfected BMSCs increased in vivo bone formation. Tissue-specific
      inhibition of miR-99a may be a potential novel therapeutic approach for enhancing
      BMSCs-based bone formation and regeneration.

PMID- 29377541
TI  - Supramolecular Nested Microbeads as Building Blocks for Macroscopic Self-Healing
      Scaffolds.
AB  - The ability to construct self-healing scaffolds that are injectable and capable
      of forming a designed morphology offers the possibility to engineer sustainable
      materials. Herein, we introduce supramolecular nested microbeads that can be used
      as building blocks to construct macroscopic self-healing scaffolds. The core
      shell microbeads remain in an "inert" state owing to the isolation of a pair of
      complementary polymers in a form that can be stored as an aqueous suspension. An
      annealing process after injection effectively induces the re-construction of the
      microbead units, leading to supramolecular gelation in a preconfigured shape. The
      resulting macroscopic scaffold is dynamically stable, displaying self-recovery in
      a self-healing electronic conductor. This strategy of using the supramolecular
      assembled nested microbeads as building blocks represents an alternative to
      injectable hydrogel systems, and shows promise in the field of structural
      biomaterials and flexible electronics.

PMID- 29377542
TI  - Domperidone upregulates dopamine receptor expression and stimulates locomotor
      activity in larval zebrafish (Danio rerio).
AB  - Dopamine (DA) plays a significant role in cognition, motor function and social
      behavior. The objectives of this study were to (1) quantify the temporal
      expression of transcripts (DA receptors, transporters and tyrosine hydroxylase)
      associated with DA signaling during early stages of zebrafish development and (2)
      determine their expression profiles following treatment with a D2 receptor
      antagonist domperidone (DMP). We also assessed locomotor behavior following
      treatment with DMP using alternating periods of light and dark (ie, dark
      photokinesis), as DA plays a key role in behavior. Relative expression levels of
      transcripts that were investigated and related to the DA system were detected
      after the first 24 hours postfertilization (hpf). Some DA receptor transcripts
      (eg, drd4c) increased in abundance earlier in the embryo compared with other
      receptors (eg, drd3), suggesting that DA receptor paralogs may have unique roles
      in development. Treatment of larvae with DMP resulted in the upregulation of DA
      receptor transcripts (ie, drd1, drd7, drd4b, drd4c) and DA transporter 1 (ie,
      slc6a3), and it is hypothesized that upregulation of genes related to the DA
      system is a compensatory neurophysiological response to DA receptor antagonism.
      Larval activity during dark photokinesis (measured by distance traveled) was also
      elevated by DMP. We hypothesize that behavioral responses observed with DMP may
      be related to the regulation of deep brain photoreception in zebrafish (Danio
      rerio) (ZF) larvae by DA.

PMID- 29377543
TI  - Novel mutation of GATA4 gene in Kurdish population of Iran with nonsyndromic
      congenital heart septals defects.
AB  - BACKGROUND: The mutations in GATA4 gene induce inherited atrial and ventricular
      septation defects, which is the most frequent forms of congenital heart defects
      (CHDs) constituting about half of all cases. METHOD: We have performed High
      resolution melting (HRM) mutation scanning of GATA4 coding exons of nonsyndrome
      100 patients as a case group including 39 atrial septal defects (ASD), 57
      ventricular septal defects (VSD) and four patients with both above defects and 50
      healthy individuals as a control group. Our samples are categorized according to
      their HRM graph. The genome sequencing has been done for 15 control samples and
      25 samples of patients whose HRM analysis were similar to healthy subjects for
      each exon. The PolyPhen-2 and MUpro have been used to determine the causative
      possibility and structural stability prediction of GATA4 sequence variation.
      RESULTS: The HRM curve analysis exhibit that 21 patients and 3 normal samples
      have deviated curves for GATA4 coding exons. Sequencing analysis has revealed 12
      nonsynonymous mutations while all of them resulted in stability structure of
      protein 10 of them are pathogenic and 2 of them are benign. Also we found two
      nucleotide deletions which one of them was novel and one new indel mutation
      resulting in frame shift mutation, and 4 synonymous variations or polymorphism in
      6 of patients and 3 of normal individuals. Six or about 50% of these
      nonsynonymous mutations have not been previously reported. CONCLUSION: Our
      results show that there is a spectrum of GATA4 mutations resulting in septal
      defects.

PMID- 29377544
TI  - A reciprocal effects analysis of cannabis use and perceptions of risk.
AB  - BACKGROUND AND AIMS: Adolescents and young adults increasingly view cannabis as a
      relatively safe drug. Perception of risk associated with cannabis use is
      correlated negatively with the prevalence of use, but the causal nature of this
      association is debated. The aim of this study is to quantitate the reciprocal
      associations between cannabis use and risk perception in a longitudinal panel of
      emerging adults. DESIGN: Observational study of longitudinal data from the
      Monitoring the Future longitudinal study using autoregressive cross-lagged panel
      analyses to investigate reciprocal associations between cannabis risk perception
      and frequency of past-year cannabis use. SETTING: Surveys administered to 12th
      grade students from the United States general population. PARTICIPANTS: A total
      of 9929 12th-grade students (mean age 18.0 years) who were surveyed initially
      during 2000-05 and follow-up data until approximately 23-24 years old (three
      waves; n = 9929). MEASUREMENTS: Perception of risk association with cannabis use
      and frequency of past-year cannabis use. RESULTS: At baseline, 33% of the 12th
      graders used cannabis in the past year versus 28% by the third follow-up; 83%
      believed that smoking cannabis regularly carried moderate or great risk versus
      78% by the third follow-up. All cross-lagged paths in both directions were
      statistically significant (all P < 0.001), consistent with reciprocal influences
      between cannabis use and risk perception. The negative association between past
      year cannabis use and subsequent risk perception (standardized coefficient range 
      0.21 to -0.27) was stronger than that between risk perception and subsequent use
      (standardized coefficient range -0.08 to -0.11; confidence intervals did not
      overlap with those for the coefficients reported above). Similar results were
      obtained when the analysis was limited to those who had never used cannabis prior
      to baseline. CONCLUSIONS: Longitudinal associations between cannabis use and
      perception of risks from cannabis use are reciprocal in nature, with a stronger
      association between cannabis use and lower subsequent risk perception.

PMID- 29377545
TI  - Synthesis and properties of blue luminescent bipolar materials constructed with
      carbazole and anthracene units with 4-cyanophenyl substitute at the 9-position of
      the carbazole unit.
AB  - With carbazole and p-cyanobromobenzene as raw materials, 4-(3,6-di (anthracen-9
      yl)-9H-carbazol-9-yl)benzonitrile (DACB) and 4-(3,6-bis(anthracene -9-ylethynyl)
      9H-carbazol-9-yl)benzonitrile (BACB) were synthesized through the Suzuki coupling
      reaction and the Sonogashira coupling reaction, respectively. These structures
      were characterized using 1 H nuclear magnetic resonance (NMR), elemental analysis
      and mass spectrometry. Their thermal properties, ultraviolet-visible (UV-vis)
      absorption, fluorescence emission, fluorescence quantum yields and
      electrochemical properties were also investigated systematically. In addition, a
      electroluminescence (EL) device was made with BACB as the emitting layer and
      performance of the EL device was studied. Results showed that: (1) the
      temperature points with 5% and 10% of DACB weight loss were 443 degrees C and 461
      degrees C, respectively, and were 475 degrees C and 506 degrees C with BACB
      weight loss of 5% and 10%, respectively. When the temperature was 50-300 degrees
      C, no significantly thermal transition was observed which suggested that they had
      excellent thermal stability. (2) DACB and BACB had single emission peaks at 415
      nm, and 479 nm with fluorescence quantum yields of 0.61 and 0.87, respectively,
      indicating that both compounds could emit strong blue light. (3) According to
      electrochemical measurement on BACB and DACB, their gaps were 3.07 eV and 2.76
      eV, respectively, which further showed that these two compounds were very stable
      and acted as efficient blue light materials. (4) The turn-on voltage of the
      device was 5 V, and the device emitted dark blue light with Commission
      Internationale de L'Eclairage (CIE) coordinates of (0.157, 0.079).

PMID- 29377546
TI  - Flawed Study Design and Incorrect Presentation of Data Negatively Impact
      Potentially Useful Interventional Treatments for Patients with Low Back Pain: A
      Critical Review of JAMA's MinT Study.

PMID- 29377547
TI  - Trapping One Electron between Three Beryllium Atoms: Very Strong One-Electron
      Three-Center Bonds.
AB  - The ability of a set of beryllium-substituted cyclohexane derivatives to trap
      electrons was determined by evaluating their electron affinities at the G4(MP2)
      level of theory. The nature of bonding and the effect of the different
      substituents attached to beryllium were studied by different computational
      methods (quantum theory of atoms in molecules, electron localization function,
      natural bond orbital, and analysis of the spin density), revealing the existence
      of a one-electron/Be3 cyclic bonding in trisubstituted species. This peculiar
      bond is the key for the high electron affinity values found in the tri-BeX
      derivatives (X=F, Cl, CN), such as the triberyllium cyano derivatives of
      cyclohexane, reaching values of 294 kJ mol-1 , only marginally smaller than the
      values reported for tetracyanoethylene (305 kJ mol-1 ) and for some fullerenes
      (306 kJ mol-1 ).

PMID- 29377548
TI  - Intracranial suppurative complications of ear, nose and throat infections: A
      single-centre cohort study of 65 patients.

PMID- 29377549
TI  - Effects of energy and thermoregulation time on physiological state and sexual
      signal in a lizard.
AB  - Theory of sexual selection states that males often develop showy signals, which
      reduce their survival but increase their reproductive success. During mate
      choice, these conspicuous signals can be honest indicators of individual quality
      conveying information about the signaler's physiological state. Sexually selected
      signals are influenced by many environmental factors; however, whether signals
      and physiological state are affected together is rarely studied. The ultraviolet
      blue throat color of male Lacerta viridis is an intra- and intersexually selected
      signal connected to blood parasite infection and influenced by environmental
      factors. The aim of this study was to experimentally investigate how ecologically
      relevant environmental factors affect color signal intensity and key
      physiological traits parallel. During the mating season, we exposed 40 adult male
      lizards infected with blood parasites to food and basking time treatments in a
      full factorial design. We measured color, amount of reactive oxygen metabolites
      (ROMs), hematocrit, immunocompetence, and blood parasite intensity before and
      after treatments. High basking time resulted in elevated immunocompetence coupled
      with increased ROMs. The high food treatment increased nuptial color brightness,
      but also increased ROMs and decreased immunocompetence. In summary, our study
      provides experimental evidence about environmentally induced parallel changes in
      an honest sexual signal and several quality-indicator physiological traits. We
      showed that available energy and time for high metabolism have independent and
      sometimes opposite effects on individual state.

PMID- 29377551
TI  - Nurse and midwifery prescribing in Ireland: A scope-of-practice development for
      worldwide consideration.
AB  - For 10 years, select Irish nurses and midwives who pass a rigorous 6 month theory
      and practical program can prescribe medications and other medicinal products.
      Given the need for timely, accessible, and affordable health-care services in all
      countries, this nursing/midwifery education and practice development is worthy of
      examination. Irish nurse/midwife prescribing occurred following long-term
      deliberative nursing profession advocacy, nursing education planning, nursing
      administration and practice planning, interdisciplinary health-care team support
      and complementary efforts, and government action. A review of documents,
      research, and other articles was undertaken to examine this development process
      and report evaluative information for consideration by other countries seeking to
      improve their health-care systems. Nurse/midwife prescribing was accomplished
      successfully in Ireland, with the steps taken there to initiate and establish
      nurse/midwife prescribing of value internationally.

PMID- 29377550
TI  - The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic
      efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.
AB  - Aberrant receptor kinase signalling and tumour neovascularization are hallmarks
      of medulloblastoma development and are both considered valuable therapeutic
      targets. In addition to VEGFR1/2, expression of PDGFR alpha/beta in particular
      has been documented as characteristic of metastatic disease correlating with poor
      prognosis. Therefore, we have been suggested that the clinically approved multi
      kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases,
      might constitute a promising option for medulloblastoma treatment. Indeed, our
      results delineate anti-neoplastic activity of Axitinib in medulloblastoma cell
      lines modelling the most aggressive c-myc-amplified Non-WNT/Non-SHH and SHH-TP53
      mutated tumours. Exposure of medulloblastoma cell lines to Axitinib results in
      marked inhibition of proliferation and profound induction of cell death. The
      differential efficacy of Axitinib is in line with target expression of
      medulloblastoma cells identifying VEGFR 1/2, PDGFR alpha/beta and c-kit as
      potential markers for drug application. The high specificity of Axitinib and the
      consequential low impact on the haematopoietic and immune system render this drug
      ideal multi-modal treatment approaches. In this context, we demonstrate that the
      clinically available PI3K inhibitor GDC-0941 enhances the anti-neoplastic
      efficacy of Axitinib against c-myc-amplified medulloblastoma. Our findings
      provide a rational to further evaluate Axitinib alone and in combination with
      other therapeutic agents for the treatment of most aggressive medulloblastoma
      subtypes.

PMID- 29377552
TI  - Cardiorespiratory fitness, exercise haemodynamics and birth outcomes: the
      Coronary Artery Risk Development in Young Adults Study.
AB  - OBJECTIVE: Determine associations of cardiorespiratory fitness, exercise systolic
      blood pressure (SBP) and heart rate recovery (HRR) following a maximal exercise
      test performed years preceding pregnancy with odds of preterm birth (PTB; <37
      weeks' gestation) and small for gestational age (SGA; birthweight <10th
      percentile) delivery. DESIGN: Prospective, longitudinal. SETTING: Multi-site,
      observational cohort study initially consisting of 2787 black and white women
      aged 18-30 at baseline (1985-86) and followed for 25 years (Y25; 2010-2011).
      POPULATION: 768 nulliparous women at baseline who reported >=1 live birth by the
      Y25 exam. METHODS: We used Poisson regression to determine associations of
      exposures with PTB/SGA. MAIN OUTCOME MEASURES: PTB and/or SGA births. RESULTS:
      Women with PTB (n = 143) and/or SGA (n = 88) were younger, had completed fewer
      years of education and were more likely to be black versus women without PTB/SGA
      (n = 546). Women with PTB/SGA had lower fitness (501 +/- 9 versus 535 +/- 6
      seconds, P < 0.002) and higher submaximal SBP than women without PTB/SGA (144 +/-
      1 versus 142 +/- 1 mmHg, P < 0.04). After adjustment, no exercise test variables
      were associated with PTB/SGA, though the association with HRR and submaximal SBP
      approached significance in the subset of women who completed the exercise test <5
      years before the index birth. CONCLUSIONS: Neither fitness nor haemodynamic
      responses to exercise a median of 5 years preceding pregnancy, were associated
      with PTB/SGA. These findings indicate excess likelihood of PTB/SGA is not
      detectable by low fitness or exercise haemodynamic responses 5 years preceding
      pregnancy, but exercise testing, especially HRR and submaximal SBP, may be more
      useful when conducted closer to the onset of pregnancy. TWEETABLE ABSTRACT:
      Exercise testing conducted >5 years before pregnancy may not detect women likely
      to have PTB/SGA.

PMID- 29377553
TI  - Two New Dolabrane Diterpenes from the Chinese Mangrove Ceriops tagal.
AB  - Two new dolabrane diterpenes, tagalenes J and K (1 and 2), together with eleven
      known analogues (3 - 13), were isolated from the ethanolic extract of the Chinese
      mangrove Ceriops tagal. The structures of these compounds were determined by
      extensive spectroscopic analysis, including 1D-, 2D-NMR and HR-ESI-MS, as well as
      the comparison with data in the literatures. Cytotoxicities of isolated compounds
      against MCF-7, SW480, HepG2, HeLa, PANC-1, and A2058 cancer cell lines were also
      evaluated. Compound 4 exhibited weak cytotoxic activity against SW480, HeLa, and
      PANC-1 cell lines with IC50 values of 27.7, 22.2, and 17.6 MUm, respectively.

PMID- 29377555
TI  - Optimization of cell growth on palmitoyl-hyaluronan knitted scaffolds developed
      for tissue engineering applications.
AB  - Polysaccharides meet several criteria for a suitable biomaterial for tissue
      engineering, which include biocompatibility and ability to support the delivery
      and growth of cells. Nevertheless, most of these polysaccharides, for example
      dextran, alginate, and glycosaminoglycans, are highly soluble in aqueous
      solutions. Hyaluronic acid hydrophobized by palmitic acid and processed to the
      form of wet-spun fibers and the warp-knitted textile scaffold is water non
      soluble, but biodegradable material, which could be used for the tissue
      engineering purpose. However, its surface quality does not allow cell attachment.
      To enhance the biocompatibility the surface of palmitoyl-hyaluronan was roughened
      by freeze drying and treated by different cell adhesive proteins (fibronectin,
      fibrinogen, laminin, methacrylated gelatin and collagen IV). Except for collagen
      IV, these proteins covered the fibers uniformly for an extended period of time
      and supported the adhesion and cultivation of dermal fibroblasts and mesenchymal
      stem cells. Interestingly, adipose stem cells cultivated on the fibronectin
      modified scaffold secreted increasing amount of HGF, SDF-1, and VEGF, three key
      growth factors involved in cardiac regeneration. These results suggested that
      palmitoyl-hyaluronan scaffold may be a promising material for various
      applications in tissue regeneration, including cardiac tissue repair. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1488-1499, 2018.

PMID- 29377554
TI  - Improved insect-proofing: expressing double-stranded RNA in chloroplasts.
AB  - RNA interference (RNAi) was discovered almost 20 years ago and has been exploited
      worldwide to silence genes in plants and animals. A decade later, it was found
      that transforming plants with an RNAi construct targeting an insect gene could
      protect the plant against feeding by that insect. Production of double-stranded
      RNA (dsRNA) in a plant to affect the viability of a herbivorous animal is termed
      trans-kingdom RNAi (TK-RNAi). Since this pioneering work, there have been many
      further examples of successful TK-RNAi, but also reports of failed attempts and
      unrepeatable experiments. Recently, three laboratories have shown that producing
      dsRNA in a plant's chloroplast, rather than in its cellular cytoplasm, is a very
      effective way of delivering TK-RNAi. Our review examines this potentially game
      changing approach and compares it with other transgenic insect-proofing schemes.
      (c) 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd
      on behalf of Society of Chemical Industry.

PMID- 29377556
TI  - Subcutaneous implantable cardioverter defibrillator in patients awaiting cardiac
      transplantation or left ventricular assist device for refractory heart failure: a
      feasible alternative to transvenous device?

PMID- 29377557
TI  - Superiorly curved scalp incision for implantation of magnetic transcutaneous bone
      conduction devices: Multicentre experience of 60 patients.

PMID- 29377558
TI  - Voltage-Gated Nanoparticle Transport and Collisions in Attoliter-Volume Nanopore
      Electrode Arrays.
AB  - Single nanoparticle analysis can reveal how particle-to-particle heterogeneity
      affects ensemble properties derived from traditional bulk measurements. High
      bandwidth, low noise electrochemical measurements are needed to examine the fast
      heterogeneous electron-transfer behavior of single nanoparticles with sufficient
      fidelity to resolve the behavior of individual nanoparticles. Herein, nanopore
      electrode arrays (NEAs) are fabricated in which each pore supports two vertically
      spaced, individually addressable electrodes. The top ring electrode serves as a
      particle gate to control the transport of silver nanoparticles (AgNPs) within
      individual attoliter volume NEAs nanopores, as shown by redox collisions of AgNPs
      collisions at the bottom disk electrode. The AgNP-nanoporeis system has wide
      ranging technological applications as well as fundamental interest, since the
      transport of AgNPs within the NEA mimics the transport of ions through cell
      membranes via voltage-gated ion channels. A voltage threshold is observed above
      which AgNPs are able to access the bottom electrode of the NEAs, i.e., a minimum
      potential at the gate electrode is required to switch between few and many
      observed collision events on the collector electrode. It is further shown that
      this threshold voltage is strongly dependent on the applied voltage at both
      electrodes as well as the size of AgNPs, as shown both experimentally and through
      finite-element modeling. Overall, this study provides a precise method of
      monitoring nanoparticle transport and in situ redox reactions within nanoconfined
      spaces at the single particle level.

PMID- 29377559
TI  - Faster Electron Injection and More Active Sites for Efficient Photocatalytic H2
      Evolution in g-C3 N4 /MoS2 Hybrid.
AB  - Herein, the structural effect of MoS2 as a cocatalyst of photocatalytic H2
      generation activity of g-C3 N4 under visible light irradiation is studied. By
      using single-particle photoluminescence (PL) and femtosecond time-resolved
      transient absorption spectroscopies, charge transfer kinetics between g-C3 N4 and
      two kinds of nanostructured MoS2 (nanodot and monolayer) are systematically
      investigated. Single-particle PL results show the emission of g-C3 N4 is quenched
      by MoS2 nanodots more effectively than MoS2 monolayers. Electron injection rate
      and efficiency of g-C3 N4 /MoS2 -nanodot hybrid are calculated to be 5.96 * 109 s
      1 and 73.3%, respectively, from transient absorption spectral measurement, which
      are 4.8 times faster and 2.0 times higher than those of g-C3 N4 /MoS2 -monolayer
      hybrid. Stronger intimate junction between MoS2 nanodots and g-C3 N4 is suggested
      to be responsible for faster and more efficient electron injection. In addition,
      more unsaturated terminal sulfur atoms can serve as the active site in MoS2
      nanodot compared with MoS2 monolayer. Therefore, g-C3 N4 /MoS2 nanodot exhibits a
      7.9 times higher photocatalytic activity for H2 evolution (660 umol g-1 h-1 )
      than g-C3 N4 /MoS2 monolayer (83.8 umol g-1 h-1 ). This work provides deep
      insight into charge transfer between g-C3 N4 and nanostructured MoS2 cocatalysts,
      which can open a new avenue for more rationally designing MoS2 -based catalysts
      for H2 evolution.

PMID- 29377560
TI  - Association of Vibrio cholerae 569B outer membrane vesicles with host cells
      occurs in a GM1-independent manner.
AB  - The primary virulence factor of Vibrio cholerae, cholera toxin (CT), initiates a
      pathway in epithelial cells that leads to the severe diarrhoea characteristic of
      cholera. Secreted CT binds to GM1 on the surface of host cells to facilitate
      internalisation. Many bacterial toxins, including CT, have been shown to be
      additionally delivered via outer membrane vesicles (OMVs). A fraction of the
      closely related heat labile toxin produced by enterotoxigenic Escherichia coli
      has been demonstrated to reside on the surface of OMVs, where it binds GM1 to
      facilitate OMV internalisation by host cells. In this work, we investigated
      whether OMV-associated CT is likewise trafficked to host cells in a GM1-dependent
      mechanism. We demonstrated that a majority of CT is secreted in its OMV
      associated form and is located exclusively inside the vesicle. Therefore, the
      toxin is unable to bind GM1 on the host cell surface, and the OMVs are trafficked
      to the host cells in a GM1-independent mechanism. These findings point to a
      secondary, noncompeting mechanism for secretion and delivery of CT, beyond its
      well-studied secretion via a Type II secretion system and underscore the
      importance of focusing future studies on understanding this GM1-independent
      delivery mechanism to fully understand Vibrio cholerae pathogenesis.

PMID- 29377561
TI  - Automatic patient positioning and gating window settings in respiratory-gated
      stereotactic body radiation therapy for pancreatic cancer using fluoroscopic
      imaging.
AB  - Before treatment delivery of respiratory-gated radiation therapy (RT) in patients
      with implanted fiducials, both the patient position and the gating window
      thresholds must be set. In linac-based RT, this is currently done manually and
      setup accuracy will therefore be dependent on the skill of the user. In this
      study, we present an automatic method for finding the patient position and the
      gating window thresholds. Our method uses sequentially acquired anterior
      posterior (AP) and lateral fluoroscopic imaging with simultaneous breathing
      amplitude monitoring and intends to reach 100% gating accuracy while keeping the
      duty cycle as high as possible. We retrospectively compared clinically used
      setups to the automatic setups by our method in five pancreatic cancer patients
      treated with hypofractionated RT. In 15 investigated fractions, the average (+/
      standard deviation) differences between the clinical and automatic setups were 
      0.4 +/- 0.8 mm, -1.0 +/- 1.1 mm, and 1.8 +/- 1.3 mm in the left-right (LR), the
      AP, and the superior-inferior (SI) direction, respectively. For the clinical
      setups, typical interfractional setup variations were 1-2 mm in the LR and AP
      directions, and 2-3 mm in the SI direction. Using the automatic method, the duty
      cycle could be improved in six fractions, in four fractions the duty cycle had to
      be lowered to improve gating accuracy, and in five fractions both duty cycle and
      gating accuracy could be improved. Our automatic method has the potential to
      increase accuracy and decrease user dependence of setup for patients with
      implanted fiducials treated with respiratory-gated RT. After fluoroscopic image
      acquisition, the calculated patient shifts and gating window thresholds are
      calculated in 1-2 s. The method gives the user the possibility to evaluate the
      effect of different patient positions and gating window thresholds on gating
      accuracy and duty cycle. If deemed necessary, it can be used at any time during
      treatment delivery.

PMID- 29377562
TI  - Automated solid-phase extraction of phenolic acids using layered double hydroxide
      alumina-polymer disks.
AB  - The application of layered double hydroxide-Al2 O3 -polymer mixed-matrix disks
      for solid-phase extraction is reported for the first time. Al2 O3 is embedded in
      a polymer matrix followed by an in situ metal-exchange process to obtain a
      layered double hydroxide-Al2 O3 -polymer mixed-matrix disk with excellent flow
      through properties. The extraction performance of the prepared disks is evaluated
      as a proof of concept for the automated extraction using sequential injection
      analysis of organic acids (p-hydroxybenzoic acid, 3,4-dihydroxybenzoic acid,
      gallic acid) following an anion-exchange mechanism. After the solid-phase
      extraction, phenolic acids were quantified by reversed-phase high-performance
      liquid chromatography with diode-array detection using a core-shell silica-C18
      stationary phase and isocratic elution (acetonitrile/0.5% acetic acid in pure
      water, 5:95, v/v). High sensitivity and reproducibility were obtained with limits
      of detection in the range of 0.12-0.25 MUg/L (sample volume, 4 mL), and relative
      standard deviations between 2.9 and 3.4% (10 MUg/L, n = 6). Enrichment factors of
      34-39 were obtained. Layered double hydroxide-Al2 O3 -polymer mixed-matrix disks
      had an average lifetime of 50 extractions. Analyte recoveries ranged from 93 to
      96% for grape juice and nonalcoholic beer samples.

PMID- 29377564
TI  - Design, Synthesis, and Biological Evaluation of Pyrazoline-Based Hydroxamic Acid
      Derivatives as Aminopeptidase N (APN) Inhibitors.
AB  - Aminopeptidase N (APN) has been recognized as a target for anticancer treatment
      due to its overexpression on diverse malignant tumor cells and association with
      cancer invasion, metastasis and angiogenesis. Herein we describe the synthesis,
      biological evaluation, and structure-activity relationship study of two new
      series of pyrazoline analogues as APN inhibitors. Among these compounds, 5-(2-(2
      (hydroxyamino)-2-oxoethoxy)phenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carboxamide
      (compound 13 e) showed the best APN inhibition with an IC50 value of 0.16+/-0.02
      MUm, which is more than one order of magnitude lower than that of bestatin (IC50
      =9.4+/-0.5 MUm). Moreover, compound 13 e was found to inhibit the proliferation
      of diverse carcinoma cells and to show potent anti-angiogenesis activity. At the
      same concentration, compound 13 e presents significantly higher anti-angiogenesis
      activity than bestatin in human umbilical vein endothelial cells (HUVECs)
      capillary tube formation assays. The putative binding mode of 13 e in the active
      site of APN is also discussed.

PMID- 29377565
TI  - The relationship between myocardial fibrosis and myocardial microRNAs in dilated
      cardiomyopathy: A link between mir-133a and cardiovascular events.
AB  - : It is unknown whether fibrosis-associated microRNAs: miR-21, miR-26, miR-29,
      miR-30 and miR-133a are linked to cardiovascular (CV) outcome. The study
      evaluated the levels of extracellular matrix (ECM) fibrosis and the prevalence of
      particular microRNAs in patients with dilated cardiomyopathy (DCM) to investigate
      any correlation with CV events. METHODS: Seventy DCM patients (48 +/- 12 years,
      EF 24.4 +/- 7.4%) underwent right ventricular biopsy. The control group was
      comprised of 7 patients with CAD who underwent CABG and intraoperative biopsy.
      MicroRNAs were measured in blood and myocardial tissue via qPCR. The end-point
      was a combination of CV death and urgent HF hospitalization at the end of 12
      months. There were differential levels of circulating and myocardial miR-26 and
      miR-29 as well as myocardial miR-133a when the DCM and CABG groups were compared.
      Corresponding circulating and myocardial microRNAs did not correlate with one
      another. There was no correlation between microRNA and ECM fibrosis. By the end
      of the 12-month period of the study, CV death had occurred in 6 patients, and a
      further 19 patients required urgent HF hospitalization. None of the circulating
      microRNAs was a predictor of the combined end-point; however, myocardial miR-133a
      was an independent predictor in unadjusted models (HR 1.53; 95% CI 1.14-2.05; P <
      .004) and adjusted models (HR 1.57; 95% CI 1.14-2.17; P < .005). The best cut-off
      value for the miR-133a level for the prediction of the combined end-point was
      0.74 DeltaCq, with an AUC of 0.67. The absence of a correlation between the
      corresponding circulating and myocardial microRNAs calls into question their
      cellular source. This study sheds new light on the role of microRNAs in ECM
      fibrosis in DCM, which warrants further exploration.

PMID- 29377566
TI  - Ribavirin dose management in HCV patients receiving
      ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin.
AB  - BACKGROUND & AIMS: Some individuals with hepatitis C virus infection treated with
      direct-acting antivirals require ribavirin to maximize sustained virological
      response rates. We describe the clinical management of ribavirin dosing in
      hepatitis C virus-infected patients receiving ombitasvir/paritaprevir/ritonavir
      and dasabuvir with ribavirin. METHODS: We performed a post hoc analysis of
      patients receiving ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin
      for 12 or 24 weeks in six phase 3 trials. Multivariate stepwise logistic
      regression models assessed predictors associated with ribavirin dose adjustments
      and with developing anaemia. RESULTS: Of 1548 patients, 100 (6.5%) modified
      ribavirin dose due to haemoglobin declines, of which 99% achieved sustained
      virological response at 12 weeks post-treatment. Median time to first ribavirin
      dose reduction was 37 days. Low baseline haemoglobin was significantly associated
      with an increased risk of requiring ribavirin dose modification (odds ratio:
      0.618 [0.518, 0.738]; P < .001) and developing anaemia (odds ratio: 0.379 [0.243,
      0.593]; P < .001). CONCLUSIONS: Ribavirin dose reductions were infrequent,
      occurred early in treatment, and did not impact sustained virological response at
      12 weeks post-treatment. Patients with low baseline haemoglobin should be
      monitored for on-treatment anaemia.

PMID- 29377568
TI  - Recent Advances of Flexible Data Storage Devices Based on Organic Nanoscaled
      Materials.
AB  - Following the trend of miniaturization as per Moore's law, and facing the strong
      demand of next-generation electronic devices that should be highly portable,
      wearable, transplantable, and lightweight, growing endeavors have been made to
      develop novel flexible data storage devices possessing nonvolatile ability, high
      density storage, high-switching speed, and reliable endurance properties.
      Nonvolatile organic data storage devices including memory devices on the basis of
      floating-gate, charge-trapping, and ferroelectric architectures, as well as
      organic resistive memory are believed to be favorable candidates for future data
      storage applications. In this Review, typical information on device structure,
      memory characteristics, device operation mechanisms, mechanical properties,
      challenges, and recent progress of the above categories of flexible data storage
      devices based on organic nanoscaled materials is summarized.

PMID- 29377567
TI  - Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4
      medulloblastoma.
AB  - Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer.
      Among the most aggressive subtypes, Group 3 and Group 4 originate from
      stem/progenitor cells, frequently metastasize, and often display the worst
      prognosis, yet we know the least about the molecular mechanisms driving their
      progression. Here, we show that the transcription factor orthodenticle homeobox 2
      (OTX2) promotes self-renewal while inhibiting differentiation in vitro and
      increases tumor initiation from MB stem/progenitor cells in vivo. To determine
      how OTX2 contributes to these processes, we employed complementary bioinformatic
      approaches to characterize the OTX2 regulatory network and identified novel
      relationships between OTX2 and genes associated with neuronal differentiation and
      axon guidance signaling in Group 3 and Group 4 MB stem/progenitor cells. In
      particular, OTX2 levels were negatively correlated with semaphorin (SEMA)
      signaling, as expression of 9 SEMA pathway genes is upregulated following OTX2
      knockdown with some being potential direct OTX2 targets. Importantly, this
      negative correlation was also observed in patient samples, with lower expression
      of SEMA4D associated with poor outcome specifically in Group 4 tumors. Functional
      proof-of-principle studies demonstrated that increased levels of select SEMA
      pathway genes are associated with decreased self-renewal and growth in vitro and
      in vivo and that RHO signaling, known to mediate the effects of SEMA genes, is
      contributing to the OTX2 KD phenotype. Our study provides mechanistic insight
      into the networks controlled by OTX2 in MB stem/progenitor cells and reveals
      novel roles for axon guidance genes and their downstream effectors as putative
      tumor suppressors in MB.

PMID- 29377569
TI  - Toxicity and effects of the neonicotinoid thiamethoxam on Scaptotrigona
      bipunctata lepeletier, 1836 (Hymenoptera: Apidae).
AB  - The neonicotinoid thiamethoxam is widely used in different agricultural crops,
      and it has a spectrum of action against insects, affecting both pests and
      pollinators, such as bees. In this study, the effects of exposure to sublethal
      concentrations of thiamethoxam on stingless bees Scaptotrigona bipunctata were
      evaluated. Foragers bees were exposed to the insecticide and subjected to genetic
      biochemical, histochemical, and morphological analyses after 24, 48, and 72 h of
      ingestion. Analysis of isoenzyme esterases revealed significant alterations in
      the relative activity of EST-4, a type II cholinesterase. Evaluation of the S.
      bipunctata brain revealed changes in the state of chromatin condensation
      according to the exposure time and concentration of neonicotinoid compared with
      the control. Morphological changes were observed in the midgut of this species at
      all concentrations and exposure times, which may interfere with various
      physiological processes of these insects. We can conclude that, although
      thiamethoxam at the concentrations evaluated did not cause high mortality, it
      induced concentration-dependent changes in bees by activating enzymes related
      with the protection for xenobiotic, internal morphology and probably these
      changes may lead to alterations in the activity of bees.

PMID- 29377570
TI  - CF3 -Inspired Synthesis of Air-Tolerant 9-Phosphaanthracenes that Feature
      Fluorescence and Crystalline Polymorphs.
AB  - 9-Phosphaanthracene (dibenzo[b,e]phosphorin, acridophosphine) has attracted
      interest as one of the heavier acenes. Herein, we demonstrate an efficient
      synthetic process that provides air-tolerant 1,8-bis(trifluoromethyl)-9
      phosphaanthracenes. The sterically encumbered and electron-withdrawing
      trifluoromethyl (CF3 ) groups are quite advantageous not only to stabilize the
      intrinsically unstable heavier unsaturated phosphorus atom but also to facilitate
      construction of the phosphinine skeleton based on a putative increase in
      aromaticity. The isolated 9-phosphaanthracenes allowed characterization of their
      fluorescence functionality and planar heteroanthracene frameworks. The crystal
      structures of 9-phosphaanthracenes are remarkably dependent on the aryl
      substituents at the 10 position; anthryl-substituted 9-phosphaanthracene showed
      unique polymorphs that induced different-colored crystals.

PMID- 29377572
TI  - Enlarging tumor of the lateral chest wall in a 14-year-old boy.

PMID- 29377571
TI  - Transcriptional Regulatory Mechanisms in Adipose and Muscle Tissue Associated
      with Composite Glucometabolic Phenotypes.
AB  - OBJECTIVE: Tissue-specific gene expression is associated with individual
      metabolic measures. However, these measures may not reflect the true but latent
      underlying biological phenotype. This study reports gene expression associations
      with multidimensional glucometabolic characterizations of obesity, glucose
      homeostasis, and lipid traits. METHODS: Factor analysis was computed by using
      orthogonal rotation to construct composite phenotypes (CPs) from 23 traits in 256
      African Americans without diabetes. Genome-wide transcript expression data from
      adipose and muscle were tested for association with CPs, and expression
      quantitative trait loci (eQTLs) were identified by associations between cis
      acting single-nucleotide polymorphisms (SNPs) and gene expression. RESULTS: The
      factor analysis identified six CPs. CPs 1 through 6 individually explained 34%,
      12%, 9%, 8%, 6%, and 5% of the variation in 23 glucometabolic traits studied.
      There were 3,994 and 929 CP-associated transcripts identified in adipose and
      muscle tissue, respectively; CP2 had the largest number of associated
      transcripts. Pathway analysis identified multiple canonical pathways from the CP
      associated transcripts. In adipose and muscle, significant cis-eQTLs were
      identified for 558 and 164 CP-associated transcripts (q-value < 0.01),
      respectively. CONCLUSIONS: Adipose and muscle transcripts comprehensively define
      pathways involved in regulating glucometabolic disorders. Cis-eQTLs for CP
      associated genes may act as primary causal determinants of glucometabolic
      phenotypes by regulating transcription of key genes.

PMID- 29377573
TI  - Intrabronchial display of hilar-mediastinal lymph nodes by virtual bronchoscopic
      navigation system.
AB  - The description of precise intrabronchial positions for the sampling of
      mediastinal-hilar lymph nodes is critical to successfully perform conventional
      transbronchial needle aspiration. Previously published maps of mediastinal-hilar
      lymph nodes were primarily drawn based on experts' experience. We generated a
      virtual map of the most frequently sampled intrathoracic lymph nodes from an
      intrabronchial perspective using a virtual bronchoscopic navigation system, to
      assist with training in conventional transbronchial needle aspiration.

PMID- 29377574
TI  - Serum alanine aminotransferase level and liver-related mortality in patients with
      chronic hepatitis B: A large national cohort study.
AB  - BACKGROUND: The serum alanine aminotransferase (ALT) level has been used to
      identify at-risk patients with chronic hepatitis B (CHB) who need antiviral
      therapy. However, the level associated with increased liver-related mortality
      requiring active treatment is still unclear. METHODS: We used a Health
      Examination Cohort of the National Health Insurance Service of Korea that
      included approximately 0.5 million individuals aged 40-79 years. In total, 12 486
      patients with CHB and no other concurrent liver disease were enrolled, and
      patients' liver-related mortality, including that owing to liver cancer, was
      investigated over 9 years. RESULTS: The serum ALT level was correlated positively
      with liver-related mortality. The rates in men were 0.14, 0.17, 0.24, 0.57, 0.63
      and 0.85 per 100 person-years (%) for serum ALT levels of <20, 20-29, 30-39, 40
      49, 50-79 and >=80 U/L, respectively, and the corresponding liver-related
      mortality rates in women were 0.03%, 0.09%, 0.12%, 0.63%, 0.65% and 0.32%. In
      patients with ALT levels of 40-79 U/L, the liver-related mortality rates were
      0.60% in men and 0.64% in women, which were similar to the overall mortality rate
      of age- and sex-matched subjects without CHB (0.69%). The best cut-off values for
      liver-related mortality prediction were >34 U/L in men and >30 U/L in women.
      CONCLUSIONS: The liver-related mortality rate increased significantly, even in
      CHB patients with relatively low serum ALT levels. Careful monitoring or earlier
      antiviral therapy should be considered for patients aged >40 years with serum ALT
      levels above the upper limit of normal.

PMID- 29377575
TI  - Biophotonics of Native Silk Fibrils.
AB  - Native silk fibroin (NSF) is a unique biomaterial with extraordinary mechanical
      and biochemical properties. These key characteristics are directly associated
      with the physical transformation of unstructured, soluble NSF into highly
      organized nano- and microscale fibrils rich in beta-sheet content. Here, it is
      shown that this NSF fibrillation process is accompanied by the development of
      intrinsic fluorescence in the visible range, upon near-UV excitation, a
      phenomenon that has not been investigated in detail to date. Here, the optical
      and fluorescence characteristics of NSF fibrils are probed and a route for
      potential applications in the field of self-assembled optically active
      biomaterials and systems is explored. In particular, it is demonstrated that NSF
      can be structured into autofluorescent microcapsules with a controllable level of
      beta-sheet content and fluorescence properties. Furthermore, a facile and
      efficient fabrication route that permits arbitrary patterns of NSF microcapsules
      to be deposited on substrates under ambient conditions is shown. The resulting
      fluorescent NSF patterns display a high level of photostability. These results
      demonstrate the potential of using native silk as a new class of biocompatible
      photonic material.

PMID- 29377577
TI  - Needs assessment survey for simulation-based training for gastrointestinal
      endoscopy nurses.
AB  - The optimal performance of gastrointestinal (GI) endoscopy nurses is required for
      patient safety and quality improvement. The aim of the present study was to
      assess the educational needs for simulation-based training for Korean GI
      endoscopy nurses using importance-performance analysis. A cross-sectional survey
      was conducted with 238 Korean nurses from 25 endoscopy units. The educational
      needs of these nurses were identified using the 35 item clinical competence
      importance-performance scale. Exploratory factor analysis of the scale identified
      the following eight factors: emergency care, patient monitoring, evidence-based
      practice, documentation and referral, patient safety, nursing process, patient
      assessment, and infection control. A significant overall mean difference was
      identified between importance and performance for all eight factors, with
      emergency care showing the largest difference. It was also ranked the highest
      priority for continuing education in the importance-performance analysis matrix.
      Therefore, simulation-based training should focus on enhancing emergency care
      competence for GI endoscopy nurses to improve patient safety and quality of care.

PMID- 29377576
TI  - Wogonoside induces depalmitoylation and translocation of PLSCR1 and N-RAS in
      primary acute myeloid leukaemia cells.
AB  - Acute myeloid leukaemia (AML) comprises a range of disparate genetic subtypes,
      involving complex gene mutations and specific molecular alterations. Post
      translational modifications of specific proteins influence their translocation,
      stability, aggregation and even leading disease progression. Therapies that
      target to post-translational modification of specific proteins in cancer cells
      represent a novel treatment strategy. Non-homogenous subcellular distribution of
      PLSCR1 is involved in the primary AML cell differentiation. However, the nuclear
      translocation mechanism of PLSCR1 remains poorly understood. Here, we leveraged
      the observation that nuclear translocation of PLSCR1 could be induced during
      wogonoside treatment in some primary AML cells, despite their genetic
      heterogeneity that contributed to the depalmitoylation of PLSCR1 via acyl protein
      thioesterase 1 (APT-1), an enzyme catalysing protein depalmitoylation. Besides,
      we found a similar phenomenon on another AML-related protein, N-RAS. Wogonoside
      inhibited the palmitoylation of small GTPase N-RAS and enhanced its trafficking
      into Golgi complex, leading to the inactivation of N-RAS/RAF1 pathway in some
      primary AML cells. Taken together, our findings provide new insight into the
      mechanism of wogonoside-induced nuclear translocation of PLSCR1 and illuminate
      the influence of N-RAS depalmitoylation on its Golgi trafficking and RAF1
      signalling inactivation in AML.

PMID- 29377578
TI  - Luminescent nanoparticles for rapid monitoring of endogenous acetylcholine
      release in mice atria.
AB  - The present work introduces for the first time a nanoparticulate approach for ex
      vivo monitoring of acetylcholinesterase-catalyzed hydrolysis of endogenous
      acetylcholine released from nerve varicosities in mice atria. Amino-modified 20
      nm size silica nanoparticles (SNs) doped by luminescent Tb(III) complexes were
      applied as the nanosensors. Their sensing capacity results from the decreased
      intensity of Tb(III)-centred luminescence due to the quenching effect of acetic
      acid derived from acetylcholinesterase-catalyzed hydrolysis of acetylcholine.
      Sensitivity of the SNs in monitoring acetylcholine hydrolysis was confirmed by in
      vitro experiments. Isolated atria were exposed to the nanosensors for 10 min to
      stain cell membranes. Acetylcholine hydrolysis was monitored optically in the
      atria samples by measuring quenching of Tb(III)-centred luminescence by acetic
      acid derived from endogenous acetylcholine due to its acetylcholinesterase
      catalyzed hydrolysis. The reliability of the sensing was demonstrated by the
      quenching effect of exogenous acetylcholine added to the bath solution.
      Additionally, no luminescence quenching occurred when the atria were pre-treated
      with the acetylcholinesterase inhibitor paraoxon.

PMID- 29377579
TI  - Identical genotypes of community-associated MRSA (ST59) and livestock-associated
      MRSA (ST9) in humans and pigs in rural China.
AB  - This study investigated the prevalence of MRSA in samples taken in households,
      with and without backyard pigs in villages in a rural area of Shandong Province,
      China. Community-associated MRSA and livestock-associated MRSA, belonging to ST59
      and ST9, respectively, were identified in both humans and pigs. The genotypic and
      phenotypic comparison of isolates indicates that bidirectional transmission of
      MRSA has occurred between humans and pigs in the villages.

PMID- 29377580
TI  - Bringing European physiologists together.

PMID- 29377581
TI  - Evaluation of calculating carboplatin dosage in carboplatin-pemetrexed therapy as
      the first-line therapy for Chinese patients with advanced lung adenocarcinoma.
AB  - OBJECTIVE: This study aims to explore the application of actual carboplatin in
      carboplatin plus pemetrexed regimen as first-line treatment for advanced lung
      adenocarcinoma, and to determine the recommended dose of carboplatin for Chinese
      populations. METHODS: From January 2014 to April 2016, 151 advanced lung
      adenocarcinoma patients who received carboplatin and pemetrexed (500 mg/m2 ) were
      included. The area under the curve (AUC) of carboplatin was back-calculated from
      actual dosages using the Calvert formula. According to the median of calculated
      AUC, patients were divided into AUC >=4 and <4 groups. RESULTS: The median of AUC
      was 4 (1.8-5.5). A total of 79 patients had an AUC >=4 and 72 patients had an AUC
      <4. The mean relative dose intensities of pemetrexed were 100.4% for the AUC >=4
      group, and 101.4% for <4 group. Baseline characteristic variables were balanced
      between the two groups, except for Eastern Cooperative Oncology Group Performance
      score (P = 0.044). The overall response rate (ORR) and disease control rate (DCR)
      were 33.8% and 90.1%, respectively, 35.4% and 86.1% for the AUC >=4 group, and
      31.9% and 94.4% for the AUC <4 group. No significant difference was observed in
      ORR (P = 0.650) and DCR (P = 0.086) between the two groups. CONCLUSION: Compared
      with an AUC of 5 or 6, the actual clinical application of AUC was generally
      insufficient for Chinese populations; fortunately, therapeutic efficacy remained
      equal. We found that AUC <4 was as adequate as AUC >=4 in pemetrexed plus
      carboplatin regimen as first-line treatment for them.

PMID- 29377582
TI  - Synthesis of a Near-Infrared BODIPY Dye for Bioimaging and Photothermal Therapy.
AB  - The development of robust photothermal agents for near-infrared (NIR) imaging is
      a great challenge. Herein, we report the design and synthesis of a new
      photothermal agent, based on the aza-boron-dipyrromethene framework (azaBDP).
      This compound possessed excellent photostability and high photothermal-conversion
      efficiency (50 %) under NIR laser irradiation. When the photothermal properties
      of this compound were utilized for tumor inhibition, stable long-term
      fluorescence was observed in living animals. Photothermal treatment efficiently
      suppressed tumor growth, as evidenced by in vitro and in vivo experiments.
      Furthermore, NIR emission could be detected by using an imaging system and
      therapeutic self-monitoring was achieved by using NIR imaging.

PMID- 29377584
TI  - Generation of full-thickness skin equivalents using hair follicle-derived primary
      human keratinocytes and fibroblasts.
AB  - Skin equivalents are increasingly used as human-based test systems for basic and
      preclinical research. Most of the established skin equivalents are composed of
      primary keratinocytes and fibroblasts, isolated either from excised human skin or
      juvenile foreskin following circumcisions. Although the potential of hair
      follicle-derived cells for the generation of skin equivalents has been shown,
      this approach normally requires microdissections from the scalp for which there
      is limited subject compliance or ethical approval. In the present study, we
      report a novel method to isolate and cultivate keratinocytes and fibroblasts from
      plucked hair follicles that were then used to generate skin equivalents. The
      procedure is non-invasive, inflicts little-pain, and may allow easy access to
      patient-derived cells without taking punch biopsies. Overall, minor differences
      in morphology, ultrastructure, expression of important structural proteins, or
      barrier function were observed between skin equivalents generated from hair
      follicle-derived or interfollicular keratinocytes and fibroblasts. Interestingly,
      improved basal lamina formation was seen in the hair follicle-derived skin
      equivalents. The presented method here allows easy and non-invasive access to
      keratinocytes and fibroblasts from plucked hair follicles that may be useful
      particularly for the generation of skin disease equivalents.

PMID- 29377583
TI  - Overexpression of geranylgeranyl diphosphate synthase contributes to tumour
      metastasis and correlates with poor prognosis of lung adenocarcinoma.
AB  - This study aimed to evaluate the biological role of geranylgeranyl diphosphate
      synthase (GGPPS) in the progression of lung adenocarcinoma. GGPPS expression was
      detected in lung adenocarcinoma tissues by qRT-PCR, tissue microarray (TMA) and
      western blotting. The relationships between GGPPS expression and the
      clinicopathological characteristics and prognosis of lung adenocarcinoma patients
      were assessed. GGPPS was down-regulated in SPCA-1, PC9 and A549 cells using siRNA
      and up-regulated in A549 cells using an adenoviral vector. The biological roles
      of GGPPS in cell proliferation, apoptosis, migration and invasion were determined
      by MTT and colony formation assays, flow cytometry, and transwell and wound
      healing assays, respectively. In addition, the regulatory roles of GGPPS on the
      expression of several epithelial-mesenchymal transition (EMT) markers were
      determined. Furthermore, the Rac1/Cdc42 prenylation was detected after knockdown
      of GGPPS in SPCA-1 and PC9 cells. GGPPS expression was significantly increased in
      lung adenocarcinoma tissues compared to that in adjacent normal tissues.
      Overexpression of GGPPS was correlated with large tumours, high TNM stage, lymph
      node metastasis and poor prognosis in patients. Knockdown of GGPPS inhibited the
      migration and invasion of lung adenocarcinoma cells, but did not affect cell
      proliferation and apoptosis. Meanwhile, GGPPS inhibition significantly increased
      the expression of E-cadherin and reduced the expression of N-cadherin and
      vimentin in lung adenocarcinoma cells. In addition, the Rac1/Cdc42
      geranylgeranylation was reduced by GGPPS knockdown. Overexpression of GGPPS
      correlates with poor prognosis of lung adenocarcinoma and contributes to
      metastasis through regulating EMT.

PMID- 29377585
TI  - Peritonsillar abscess: A retrospective case series of 1773 patients.

PMID- 29377586
TI  - A Universal Upconversion Sensing Platform for the Sensitive Detection of Tumour
      Related ncRNA through an Exo III-Assisted Cycling Amplification Strategy.
AB  - Here, a sensitive and universal noncoding RNA (ncRNA) upconversion sensing
      nanoplatform is developed. Gold nanoparticles bearing one hairpin DNA (Hp)
      molecule are conjugated to the linker DNA modified NaYF4 :Yb, Er@NaYF4
      upconversion nanoparticles by DNA hybridization, leading to quenching of the
      upconversion emission through fluorescence resonance energy transfer. A signal
      DNA (SDNA) sequence is designed to open Hp, recovering the upconversion emission.
      To achieve universality and high sensitivity of the nanoprobe, an exonuclease III
      (Exo III)-assisted cycling amplification strategy is introduced. A
      multifunctional hairpin DNA (mHp) containing ncRNA recognition sequence and SDNA
      sequence is designed to recognize ncRNA and trigger Exo III as a biocatalyst to
      stepwise disintegrate itself, releasing both ncRNA and SDNA. The released ncRNA
      can be reused to release more SDNA, which greatly improves the sensing
      sensitivity. By changing the recognition portion of mHp, various ncRNA can be
      detected. The sensitive detection of both homeobox (HOX) transcript antisense RNA
      segment and miR-21 is achieved with this novel strategy, even in human serum,
      indicating the universality and sensitivity of the proposed strategy.
      Additionally, the expression level of miR-21 in human breast cancer cell (MCF-7)
      lysate is successfully measured, suggesting its potential in clinical diagnosis.

PMID- 29377587
TI  - Lactate increases myotube diameter via activation of MEK/ERK pathway in C2C12
      cells.
AB  - AIM: Lactate is produced in and released from skeletal muscle cells. Lactate
      receptor, G-protein-coupled receptor 81 (GPR81), is expressed in skeletal muscle
      cells. However, a physiological role of extracellular lactate on skeletal muscle
      is not fully clarified. The purpose of this study was to investigate
      extracellular lactate-associated morphological changes and intracellular signals
      in C2C12 skeletal muscle cells. METHODS: Mouse myoblast C2C12 cells were
      differentiated for 5 days to form myotubes. Sodium lactate (lactate) or GPR81
      agonist, 3,5-dihydroxybenzoic acid (3,5-DHBA), was administered to the
      differentiation medium. RESULTS: Lactate administration increased the diameter of
      C2C12 myotubes in a dose-dependent manner. Administration of 3,5-DHBA also
      increased myotube diameter. Not only lactate but also 3,5-DHBA upregulated the
      phosphorylation level of mitogen-activated protein kinase kinase 1/2 (MEK1/2),
      p42/44 extracellular signal-regulated kinase-1/2 (ERK1/2) and p90 ribosomal S6
      kinase (p90RSK). MEK inhibitor U0126 depressed the phosphorylation of ERK-p90RSK
      and increase in myotube diameter induced by lactate. On the other hand, both
      lactate and 3,5-DHBA failed to induce significant responses in the
      phosphorylation level of Akt, mammalian target of rapamycin, p70 S6 kinase and
      protein degradation-related signals. CONCLUSION: These observations suggest that
      lactate-associated increase in the diameter of C2C12 myotubes is induced via
      activation of GRP81-mediated MEK/ERK pathway. Extracellular lactate might have a
      positive effect on skeletal muscle size.

PMID- 29377589
TI  - Nitric oxide-releasing antibacterial albumin plastic for biomedical applications.
AB  - Designing innovative materials for biomedical applications is desired to prevent
      surface fouling and risk of associated infections arising in the surgical care
      patient. In the present study, albumin plastic was fabricated and nitric oxide
      (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), was incorporated through a
      solvent swelling process. The albumin-SNAP plastic was evaluated in terms of
      mechanical and thermal properties, and bacterial adhesion to the plastic surface.
      Thermal and viscoelastic analyses showed no significant difference between
      albumin-SNAP plastics and pure, water-plasticized albumin samples. Bacteria
      adhesion tests revealed that albumin-SNAP plastic can significantly reduce the
      surface-bound viable gram-positive Staphylococcus aureus and gram-negative
      Pseudomonas aeruginosa bacterial cells by 98.7 and 98.5%, respectively, when
      compared with the traditional polyvinyl chloride medical grade tubing material.
      The results from this study demonstrate NO-releasing albumin plastic's potential
      as a material for biomedical device applications. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1535-1542, 2018.

PMID- 29377590
TI  - Evaluation of pulmonary reexpansion in a porcine model of bronchial foreign body.
AB  - OBJECTIVES: This study was designed to establish a porcine model of reversible
      obstruction of endobronchial foreign body (FB) and to assess the natural
      pulmonary reexpansion process using radiology and histopathology after removal of
      the bronchial FB. METHODS: A metal stent was placed in the right lower lobe
      bronchial lumen of 15 pigs by bronchoscopy and removed after 2 weeks of stent
      retention. Animals were divided into two groups (group I and II), based on when
      they were sacrificed (week 2 or week 4) after stent removal. Pigs underwent
      computerized tomography scan to document pulmonary radiological changes. The
      lungs were harvested for electron microscopy examination, and the expression of
      pulmonary surfactant-associated protein A (SPA) was determined by
      immunohistochemistry. RESULTS: Thirteen (86.7%) animals successfully responded to
      the intervention. Atelectasis was formed by stent implantation within 2 weeks.
      The ratio of the residual atelectasis area was smaller in group II compared to
      that in group I (P < 0.01). The histological manifestations of experimental lungs
      were significantly improved in group II. Moreover, the expression of SPA in group
      II was higher compared to that in group I (P < 0.01). CONCLUSIONS: We have
      established a model of reversible bronchial FB obstruction in pigs that is both
      feasible and appropriate for evaluating the long-term process of pulmonary
      reexpansion after removal of FB. Bronchial metal FB retention for a period of 2
      weeks could form atelectasis, and a natural pulmonary recovery process related to
      atelectasis takes approximately 4 weeks after removal of metal FB.

PMID- 29377588
TI  - A robust gene signature for the prediction of early relapse in stage I-III colon
      cancer.
AB  - Colon cancer patients experiencing early relapse consistently exhibited poor
      survival. The aim of our study was to develop an mRNA signature that can help to
      detect early relapse cases in stage I-III colon cancer. Public microarray
      datasets of stage I-III colon cancer samples were extracted from the Gene
      Expression Omnibus database. Propensity score matching analysis was performed
      between patients in the early relapse group and the long-term survival group from
      GSE39582 discovery series (N = 386), and patients were 1 : 1 matched. Global mRNA
      expression changes were then analyzed between the paired groups to identify the
      differentially expressed genes. Lasso Cox regression modeling analysis was
      conducted for the selection of prognostic mRNA. Fifteen mRNA were finally
      identified to build an early relapse classifier. With specific risk score
      formula, patients were classified into a high-risk group and a low-risk group.
      Relapse-free survival was significantly different between the two groups in every
      series, including discovery [hazard ratio (HR): 2.547, 95% confidence interval
      (CI): 1.708-3.797, P < 0.001)], internal validation (HR: 5.146, 95% CI: 1.968
      13.457, P < 0.001), and external validation (HR: 1.977, 95% CI: 1.295-3.021, P <
      0.001) sets of patients. Time-dependent receiver-operating characteristic at 1
      year suggested more prognostic accuracy of the classifier [area under curve (AUC
      = 0.703)] than the American Joint Commission on Cancer tumor-node-metastasis
      staging system (AUC = 0.659) in all 951 patients. In conclusion, we developed a
      robust mRNA signature that can effectively classify colon cancer patients into
      groups with low and high risks of early relapse. This mRNA signature may help
      select high-risk colon cancer patients who require more aggressive therapeutic
      intervention.

PMID- 29377591
TI  - Carboxylated graphene oxide promoted axonal guidance growth by activating Netrin
      1/deleted in colorectal cancer signaling in rat primary cultured cortical
      neurons.
AB  - Nanomaterials of graphene and its derivatives have been widely applied in recent
      years, but whose impacts on the neuronal guidance growth are still not reported.
      In the present study, graphene oxide (GO) and carboxylated graphene oxide (GO
      COOH) were used to investigate the potential effects on axonal guidance growth in
      the primary cultured cortical neurons. In addition, we characterized the
      structure and chemical composition of synthesized GO and GO-COOH using Fourier
      transform infrared spectrophotometer and scanning electron microscope assays and
      Raman analysis. GO is not neurotoxic and not conductive in a soluble form.
      However, GO-COOH has higher solubility and conductivity. Cell viability was
      assessed using CCK-8 assays and fluorescein diacetate after GO and GO-COOH
      treatment (0, 1, 2, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 50, and 100 ug/mL). There
      are significant increases of cell viability and axonal growth after GO (2 and 4
      MUg/mL) and GO-COOH treatment (2 and 4 MUg/mL). We further investigated the
      molecular mechanism of axonal guidance growth after GO and GO-COOH (2 and 4
      MUg/mL) application. Additionally, GO and GO-COOH up-regulated expression of
      Netrin-1 and its receptor, deleted in colorectal cancer by immunofluorescence
      assays and western blots assay. Our study demonstrated that GO-COOH activated
      Cdc42 and Rac1 and dramatically decreased RhoA. Thus, GO-COOH (2 ug/mL) is much
      better to be nanocarriers than GO for axonal guidance and growth in this study.
      GO-COOH may be used to facilitate guidance for regenerating neurons in the
      future. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1500
      1510, 2018.

PMID- 29377592
TI  - Dairy Protein Supplementation Modulates the Human Skeletal Muscle microRNA
      Response to Lower Limb Immobilization.
AB  - Limb immobilization results in a rapid loss of muscle size and strength. The
      resultant alterations in signaling pathways governing myogenesis, catabolism, and
      mitochondrial biogenesis are likely to include posttranscriptional regulation
      mediated by altered microRNAs (miRNAs). Given that protein ingestion exerts an
      anabolic action and may act as a countermeasure to mitigate muscle loss with
      immobilization, it is important to examine miRNA in this context. The objective
      of the study is therefore to characterize the vastus lateralis miRNA response to
      14 days of disuse in males (45-60 years) randomized to receive supplementation
      with 20 g d-1 of dairy protein (n = 12) or isocaloric carbohydrate placebo (n =
      13). Biopsies are collected before and after a 2-week immobilization period. Of
      the 24 miRNAs previously identified in myogenic regulation, seven (miR-133a, 
      206, -15a, -451a, -126, -208b, and let-7e) are increased with immobilization
      irrespective of group; five (miR-16, -494, let-7a, -7c, and 7d) increased only in
      the carbohydrate group; and eight (miR-1, -486, -23a, -23b, -26a, -148b, let-7b,
      and -7g) are divergently expressed between groups (suppressed with protein). The
      ability of protein supplementation to differentially regulate miRNAs involved in
      key muscle regulatory pathways following short-term limb immobilization reflects
      potential protective function in mitigating muscle loss during limb
      immobilization.

PMID- 29377593
TI  - Diabetes-related cognitive dysfunction: Hyperglycemia in the early stage might be
      a key?

PMID- 29377594
TI  - Spatial epidemiology of amyotrophic lateral sclerosis in Piedmont and Aosta
      Valley, Italy: a population-based cluster analysis.
AB  - BACKGROUND AND PURPOSE: The analysis of the spatial distribution of cases could
      give important cues on putative environmental causes of a disease. Our aim was to
      perform a spatial analysis of an amyotrophic lateral sclerosis (ALS) cohort from
      the Piedmont and Aosta Valley ALS register (PARALS) over a 20-year period.
      METHODS: The address at the moment of diagnosis was considered for each ALS case.
      Municipalities' and census divisions' resident populations during the 1995-2014
      period were obtained. A cluster analysis was performed adopting both Moran's
      index and the Kulldorff spatial scan statistic. RESULTS: A total of 2702 ALS
      patients were identified. An address was retrieved for 2671 (99%) patients.
      Moran's index was -0.01 (P value 0.83), thus revealing no clusters. SaTScan
      identified no statistically significant clusters. When census divisions were
      considered, Moran's index was 0.13 (P value 0.45); SaTScan revealed one
      statistically significant small cluster in the province of Alessandria. Here,
      0.0099 cases were expected and three cases were observed (relative risk 304.60;
      95% confidence interval 109.83-845.88, P value 0.03). DISCUSSION: Our study
      showed a substantial homogeneous distribution of ALS cases in Piedmont and Aosta
      Valley. The population-based setting and the adoption of proper statistical
      analyses strengthen the validity of our results. Such a finding further suggests
      the involvement of multiple environmental and genetic factors in ALS
      pathogenesis.

PMID- 29377595
TI  - Silicon carbide nanomaterial as a coating for solid-phase microextraction.
AB  - Silicon carbide has excellent properties, such as corrosion resistance, high
      strength, oxidation resistance, high temperature, and so on. Based on these
      properties, silicon carbide was coated on stainless-steel wire and used as a
      solid-phase microextraction coating, and polycyclic aromatic hydrocarbons were
      employed as model analytes. Using gas chromatography, some important factors that
      affect the extraction efficiency were optimized one by one, and an analytical
      method was established. The analytical method showed wide linear ranges (0.1-30,
      0.03-30, and 0.01-30 MUg/L) with satisfactory correlation coefficients (0.9922
      0.9966) and low detection limits (0.003-0.03 MUg/L). To investigate the practical
      application of the method, rainwater and cigarette ash aqueous solution were
      collected as real samples for extraction and detection. The results indicate that
      silicon carbide has excellent application in the field of solid-phase
      microextraction.

PMID- 29377596
TI  - Processing of Citrus Nanostructured Cellulose: A Rigorous Design-of-Experiment
      Study of the Hydrothermal Microwave-Assisted Selective Scissoring Process.
AB  - A detailed design-of-experiment (DoE) study to investigate the cause-effect
      interactions of three process variables, that is, temperature (120-200  degrees
      C), holding time (0-30 min), and concentration (1.4-5.0 wt %), on the processing
      of citrus cellulosic matter using acid-free microwave-assisted selective
      scissoring (Hy-MASS) is reported. Analysis of variance (ANOVA) showed that post
      microwave processing, the yield of cellulosic matter (25-72 %), decomposition
      temperature (345-373  degrees C), and crystallinity index (34-67 %) were strongly
      affected by temperature. SEM and TEM analyses showed that the isolated cellulosic
      matter was heterogeneous and consisted of a mixture of micro- and nanofibers more
      akin to microfibrillated cellulose (MFC) at low processing temperatures and
      tending towards aggregated cellulose nanofibrils (CNFs) and cellulose
      nanocrystals (CNCs) at higher processing temperatures. The water holding capacity
      of the processed cellulosic matter (15-27 gH2O  g-1 ) was higher than the
      original feedstock or previously reported values. The average molecular weight of
      the cellulosic matter (113.6-1095.9 kg mol-1 ) decreased significantly by a
      factor of 10 at operating temperatures above 180  degrees C, invoking significant
      scissoring of the cellulosic chains. The process energy input and costs varied
      between 0.142-0.624 kWh and 13-373 ? kg-1 , respectively, and strongly depended
      on the reaction time.

PMID- 29377597
TI  - A Phytol-Enriched Diet Activates PPAR-alpha in the Liver and Brown Adipose Tissue
      to Ameliorate Obesity-Induced Metabolic Abnormalities.
AB  - SCOPE: Peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a ligand
      activated transcription factor that regulates lipid and carbohydrate metabolism.
      We investigate the effects of naturally occurring PPAR-alpha agonists, phytol,
      and its metabolite phytanic acid, on obesity-induced metabolic disorders using a
      mouse model. METHODS AND RESULTS: A luciferase reporter assay shows that phytanic
      acid potently activates PPAR-alpha among PPAR subtypes. In high-fat-diet-induced,
      severely obese mice, a phytol-enriched diet increases phytanic acid levels in the
      liver and adipose tissue, where PPAR-alpha is abundantly expressed. A phytol
      enriched diet ameliorates severe obesity and the related metabolic abnormalities
      of white adipose tissue. Moreover, the expression of PPAR-alpha target genes in
      the liver and brown adipose tissue is enhanced by a phytol-enriched diet,
      suggesting that phytol and phytanic acid activate PPAR-alpha in these organs. We
      confirm that phytanic acid treatment induced PPAR-alpha target gene expression in
      both primary hepatocytes and brown adipocytes from wild-type mice, but not in
      these cells from PPAR-alpha-deficient mice. CONCLUSION: A phytol-enriched diet
      may increase phytanic acid levels in the liver and brown adipocytes, thereby
      activating PPAR-alpha in these organs and ameliorating obesity-induced metabolic
      diseases.

PMID- 29377599
TI  - Core/shell cellulose-based microspheres for oral administration of Ketoprofen
      Lysinate.
AB  - Herein, we propose the fabrication of a new carrier with core/shell structure
      inner core of cellulose acetate (CA) coated by a micrometric layer of chitosan
      (CS)-fabricated through an integrated process, which combines Electro Dynamic
      Atomization (EDA) and layer-by-layer (LbL) technique. We demonstrate that CA
      based microspheres possess a unique capability to relevantly retain the drugs
      that is, Ketoprofen Lysinate (KL)-along the gastric tract, while providing a
      massive release along the intestine. CS shell slightly influences the morphology
      and water retention under different pH conditions, improving drug encapsulation
      without compromising drug release kinetics. In vitro studies in simulated gastric
      and intestine fluids (SGF, SIF) with physiological enzymes, show a moderate
      release of LSK during the first 2 h (ca. 20% at pH 2), followed by a sustained
      release during the next 6 h (ca. 80% at pH 7). The obtained results demonstrate
      that CA-based microspheres hold strong potential to be used as carriers for a
      delayed oral administration of anti-inflammatory drugs. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2636-2644,
      2018.

PMID- 29377598
TI  - Graphs of study contributions and covariate distributions for network meta
      regression.
AB  - BACKGROUND: Meta-regression results must be interpreted taking into account the
      range of covariate values of the contributing studies. Results based on
      interpolation or extrapolation may be unreliable. In network meta-regression
      (NMR) models, which include covariates in network meta-analyses, results are
      estimated using direct and indirect evidence; therefore, it may be unclear which
      studies and covariate values contribute to which result. We propose graphs to
      help understand which trials and covariate values contribute to each NMR result
      and to highlight extrapolation or interpolation. METHODS: We introduce methods to
      calculate the contribution that each trial and covariate value makes to each
      result and compare them with existing methods. We show how to construct graphs
      including a network covariate distribution diagram, covariate-contribution plot,
      heat plot, contribution-NMR plot, and heat-NMR plot. We demonstrate the methods
      using a dataset with treatments for malaria using the covariate average age and a
      dataset of topical fluoride interventions for preventing dental caries using the
      covariate randomisation year. RESULTS: For the malaria dataset, no contributing
      trials had an average age between 7-25 years and therefore results were
      interpolated within this range. For the fluoride dataset, there are no
      contributing trials randomised between 1954-1959 for most comparisons therefore,
      within this range, results would be extrapolated. CONCLUSIONS: Even in a fully
      connected network, an NMR result may be estimated from trials with a narrower
      covariate range than the range of the whole dataset. Calculating contributions
      and graphically displaying them aids interpretation of NMR result by highlighting
      extrapolated or interpolated results.

PMID- 29377600
TI  - Activation of TNF-alpha/NF-kappaB axis enhances CRL4BDCAF11 E3 ligase activity
      and regulates cell cycle progression in human osteosarcoma cells.
AB  - Cullin 4B, a member of the Cullins, which serve as scaffolds to facilitate the
      assembly of E3 ligase complexes, is aberrantly expressed in many cancers,
      including osteosarcoma. Recently, we observed that CUL4B forms the CRL4BDCAF11 E3
      ligase, which specifically ubiquitinates and degrades the cyclin-dependent kinase
      (CDK) inhibitor p21Cip1 in human osteosarcoma cells. However, the underlying
      mechanisms regarding the aberrant expression of CUL4B and the upstream members of
      this signaling pathway are mostly unknown. In this study, we demonstrate that
      nuclear factor kappaB (NF-kappaB) is a direct modulator of CUL4B expression. The
      CUL4B promoter is responsive to several NF-kappaB subunits, including RelA, RelB,
      and c-Rel, but not to p50 or p52. Additional studies reveal that the tumor
      necrosis factor alpha (TNF-alpha)/NF-kappaB axis pathway is activated in human
      osteosarcoma cells. This activation causes both CUL4B and NF-kappaB subunits to
      become abundant in the nucleus of human osteosarcoma cells. The down-regulation
      of individual genes, including TNFR1, RelA, RelB, c-Rel, and CUL4B, or pairs of
      them, including TNFR1 + RelA, TNFR1 + RelB, TNFR1 + c-Rel, and RelA+CUL4B, has
      similar effects on cell growth inhibition, colony formation, cell invasion, and
      in vivo tumor formation, whereas the overexpression of CUL4B in these knockdown
      cells significantly reverses their phenotypes. The inhibition of the TNF-alpha/NF
      kappaB pathway greatly attenuates CRL4BDCAF11 E3 ligase activity and causes the
      accumulation of p21Cip1 , thereby leading to cell cycle arrest at the S phase.
      Taken together, our results support a model in which the activation of the TNF
      alpha/NF-kappaB axis contributes to an increase in CRL4BDCAF11 activity and a
      decrease in p21Cip1 protein levels, thereby controlling cell cycle progression in
      human osteosarcoma cells.

PMID- 29377601
TI  - Defect-Free Mixed-Matrix Membranes with Hydrophilic Metal-Organic Polyhedra for
      Efficient Carbon Dioxide Separation.
AB  - Defect-free mixed-matrix membranes (MMMs) were prepared by incorporating
      hydrophilic metal-organic polyhedra (MOPs) into cross-linked polyethylene oxide
      (XLPEO) for efficient CO2 separation. Hydrophilic MOPs with triethylene glycol
      pendant groups, which were assembled by 5-tri(ethylene glycol) monomethyl ether
      isophthalic acid and CuII ions, were uniformly dispersed in XLPEO without
      particle agglomeration. Compared to conventional neat XLPEO, the homogenous
      dispersion of EG3 -MOPs in XLPEO enhanced CO2 permeability of MMMs. Upon
      increasing the amount of EG3 -MOPs, the membrane performance such as CO2 /N2
      selectivity was steadily improved because of unsaturated CuII sites at paddle
      wheel units, which was confirmed by Cu K-edge XANES and TPD analysis. Therefore,
      such defect-free MMMs with unsaturated metal sites would contribute to enhance
      CO2 separation performance.

PMID- 29377602
TI  - Dielectrophoresis-Based Protein Enrichment for a Highly Sensitive Immunoassay
      Using Ag/SiO2 Nanorod Arrays.
AB  - A nanoscale insulator-based dielectrophoresis (iDEP) technique is developed for
      rapid enrichment of proteins and highly sensitive immunoassays. Dense arrays of
      nanorods (NDs) by oblique angle deposition create a super high electric field
      gradient of 2.6 * 1024 V2 m-3 and the concomitant strong dielectrophoresis force
      successfully traps small proteins at a bias as low as 5 V. 1800-fold enrichment
      of bovine serum albumin protein at a remarkable rate of up to 180-fold s-1 is
      achieved using oxide coated Ag nanorod arrays with pre-patterned sawtooth
      electrodes. Based on this system, an ultrasensitive immunoassay of mouse
      immunoglobulin G is demonstrated with a reduction in the limit of detection from
      5.8 ng mL-1 (37.6 pM) down to 275.3 fg mL-1 (1.8 f M), compared with identical
      assays performed on glass plates. This methodology is also applied to detect a
      cancer biomarker prostate-specific antigen spiked in human serum with a detection
      limit of 2.6 ng mL-1 . This high sensitivity results from rapid biomarker
      enrichment and metal enhanced fluorescence through the integration of
      nanostructures. The concentrated proteins also accelerate binding kinetics and
      enable signal saturation within 1 min. Given the easy fabrication process, this
      nanoscale iDEP system provides a highly sensitive detection platform for point-of
      care diagnostics.

PMID- 29377604
TI  - Community social deprivation and solid organ transplant outcomes.

PMID- 29377603
TI  - Effects of Ojeok-san on the Pharmacokinetics of Celecoxib at Steady-state in
      Healthy Volunteers.
AB  - Ojeok-san is a frequently used herbal medication for the management of
      osteoarthritic pain. We evaluated the effect of Ojeok-san on the pharmacokinetics
      of celecoxib at steady-state in healthy individuals. An open-label, fixed
      sequence, two-period, two-treatment cross-over study was conducted. In period I,
      the individuals received celecoxib capsule 200 mg once daily for 4 days. In
      period II, only Ojeok-san (14.47 g/pack, three times daily) was administered for
      4 days, followed by co-administration with celecoxib for 4 days. On the fourth
      (final) day of administration, Ojeok-san was administered as a single dose. The
      blood samples for pharmacokinetic evaluation were collected for up to 48 hr after
      the administration of celecoxib in each study period. Of the 22 enrolled
      individuals, 20 individuals completed the study. In the presence of Ojeok-san,
      the systemic exposure of celecoxib was decreased. The geometric mean ratios
      ([celecoxib + Ojeok-san]/celecoxib) and the 90% confidence intervals for the
      maximum plasma concentration (Cmax ) and the area under the plasma concentration
      time curve during dosing interval (AUCtau ) of celecoxib at steady-state were
      0.725 (0.620-0.848) and 0.885 (0.814-0.962), respectively. The changes in the
      mean of the Cmax and AUCtau of celecoxib were greater in intermediate
      metabolizers of cytochrome 2C9 (CYP2C9) than in normal metabolizers. Our results
      suggested that the Cmax and AUCtau of celecoxib were reduced by Ojeok-san co
      administration. This finding may be beneficial to determine the required
      adjustment of celecoxib dosage when co-administered with Ojeok-san.

PMID- 29377605
TI  - Single vs multiallergen sublingual immunotherapy in the polysensitized patient: a
      pilot study.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) has emerged as an effective and
      exceptionally safe method of treatment of the atopic patient. However, the
      optimal number of allergens that should be included in the SLIT treatment regimen
      for the polysensitized patient is not known and practices vary widely. This study
      aims to compare the efficacy of single-allergen SLIT with pauci-allergen vs
      multiallergen aqueous SLIT in polysensitized patients. METHODS: Sixteen subjects
      sensitized to 6+ allergens were enrolled in the study. Subjects were blinded and
      randomized to SLIT treatment groups that included 1 (single), 3 (pauci), or all
      sensitized allergens (multi). Allergens selected were those to which the patient
      was most sensitized and correlated with history. Primary outcomes included daily
      allergy medication use, weekly Rhinoconjunctivitis Symptom Score (RCSS), and the
      mini-Rhinoconjuncitivitis Quality of Life Questionnaire (m-RQLQ). All metrics
      were measured at baseline, 6 weeks, 3 months, 6 months, and 9 months. RESULTS:
      There were significant decreases from baseline in RCSS and m-RQLQ scores in all
      study groups at each interval after beginning SLIT (p < 0.05). There was no
      significant decrease in number of daily allergy medications used regardless of
      number of allergens in patient's treatment vial (p = 0.50). No significant
      differences emerged based on number of allergens used. CONCLUSION: Single
      antigen, pauci-antigen, and multiantigen aqueous SLIT significantly improved
      allergy symptoms. There was no significant difference observed in efficacy of
      single-allergen SLIT vs pauci-allergen or multi-allergen SLIT in polysensitized
      patients.

PMID- 29377606
TI  - High Capacitive Storage Performance of Sulfur and Nitrogen Codoped Mesoporous
      Graphene.
AB  - Mesoporous graphene is synthesized based on the chemical vapor deposition
      methodology by using heavy MgO flakes as substrates in a fluidized-bed reactor.
      Subsequently, sulfur and nitrogen coincorporation into graphene frameworks is
      realized by the reaction between carbon atoms and thiourea molecules. The as
      obtained sulfur and nitrogen codoped mesoporous graphene (SNMG) exhibits
      remarkable capacitive energy-storage behavior, as a result of well-developed pore
      channels, in terms of that in a symmetric supercapacitor and lithium-ion hybrid
      capacitor (LIHC). The ultrahigh durability of the SNMG/SNMG symmetric
      supercapacitor is demonstrated by long-term cycling, for which no capacitance
      decay is found after 20 000 cycles. A LIHC constructed from commercial Li4 Ti5
      O12 (LTO) as the anode and SNMG as the cathode is capable of delivering much
      enhanced lithium-storage ability and better rate capability than that of
      activated carbon (AC)/LTO LIHC. Moreover, SNMG/LTO LIHC exhibits maximum energy
      and power densities of 86.2 Wh kg-1 and 7443 W kg-1 and maintains 87 %
      capacitance retention after 2000 cycles.

PMID- 29377608
TI  - Biosimilars and patient care.

PMID- 29377607
TI  - Immunosuppressants produced by Streptomyces: evolution, hygiene hypothesis,
      tumour rapalog resistance and probiotics.
AB  - Resistance to a drug and the suppression of inflammatory disorders with
      immunosuppressive drugs might have happened upon exposure to natural compounds
      during evolution. Streptomycetes are soil bacteria, but they produce therapeutic
      drugs. They have been reported to be the low-abundant members of mucosal
      microbiomes with a higher prevalence in nonhumans ingesting soil compared with
      humans. Their lower abundance in the human microbiome might be the
      representations of our current hygienic lifestyle. We suggest that the
      Streptomyces bacteria producing antiproliferative/immunosuppressive compounds
      (e.g., rapamycin and tacrolimus) contribute to the rapalog resistance of certain
      mucosal tumours (e.g., colon cancer) and the 'hygiene hypothesis'. If so, the
      shortage of exposure to these compounds in the current lifestyle might be an
      underlying reason for the increase of inflammatory diseases, such as inflammatory
      bowel diseases (IBD). An investigation on adding certain Streptomycetes (e.g., S.
      hygroscopicus and S. tubercidicus) to the list of probiotics against inflammatory
      diseases would be an interesting research area in the future.

PMID- 29377609
TI  - Use of the Fractional Excretion of Urea in an Azotemic Nonoliguric State: Type 1
      Cardiorenal Syndrome.
AB  - The fractional excretion of urea is a useful tool to evaluate renal function in
      oliguric states; however, it remains unexplored in nonoliguric states. We
      evaluated its use to predict responses in patients with type 1 cardiorenal
      syndrome. This was a prospective observational study of 116 patients with type 1
      cardiorenal syndrome referred over a 4-year period. Fractional excretion of urea
      and sodium, ejection fraction, mean arterial pressure, age, sex, diabetes, brain
      natriuretic peptide (BNP), serum sodium and blood urea nitrogen were analyzed for
      effects upon serum creatinine and survival. Improvement of renal function
      correlated most significantly with FeUrea (P = 0.00001) followed by the FeNa (P =
      0.005) but no other variable studied reached significance. Survival was best
      predicted by improvement of the serum creatinine at 24 h (P = 0.005) and 7 days
      after all inotropes were stopped (P = 0.001). A limitation of this study is that
      it cannot be extrapolated to all cardiorenal syndrome patients other than type 1.
      Also, the study was not randomized and those with potentially worse disease have
      had worse outcomes due merely to worse underlying disease. The success of the
      FeUrea may possibly be related to interference of dobutamine on creatinine
      levels. Despite being a nonoliguric state, the FeUrea appears to provide insight
      to those patients with type 1 cardiorenal syndrome whose renal function (as
      measured by serum creatinine) and survival might improve.

PMID- 29377610
TI  - TePtFe Nanotubes as High-Performing Bifunctional Electrocatalysts for the Oxygen
      Reduction Reaction and Hydrogen Evolution Reaction.
AB  - Currently, a multicomponent platinum-based alloy has been applied as a promising
      electrocatalyst to improve catalysis and lower the usage of the noble metal
      platinum. Herein, a tellurium nanowire (NW)-derived ternary TePtFe nanotube (NT)
      electrocatalyst has been prepared by the Kirkendall effect. The TePtFe NT formed
      consists of small single-crystal nanoparticles and voids with an open-end and
      hollow structure. The TePtFe NT electrocatalyst presents an impressive catalytic
      activity and stability for both the oxygen reduction reaction (ORR) and hydrogen
      evolution reaction (HER). Its ORR specific activity and mass activity are 8.5 and
      2.4 times, respectively, improved relative to those of commercial platinum
      catalysts. It is also impressive that, for the HER, a very low overpotential of
      28.1 mV at 10 mA cm-2 can be achieved; this is lower than that of platinum (51.8
      mV) catalysts in 0.1 m HClO4 , and the activity is improved, even after 5000
      cycles. This work reveals that TePtFe NTs can be employed as nanocatalysts with
      an impressive catalytic activity and stability for application in fuel cells and
      hydrogen production.

PMID- 29377612
TI  - Applying the Ts of referred otalgia to a cohort of 226 patients.

PMID- 29377611
TI  - Developmental social communication deficits in the Shank3 rat model of phelan
      mcdermid syndrome and autism spectrum disorder.
AB  - : Mutations in the SHANK3 gene have been discovered in autism spectrum disorder
      (ASD), and the intellectual disability, Phelan-McDermid Syndrome. This study
      leveraged a new rat model of Shank3 deficiency to assess complex behavioral
      phenomena, unique to rats, which display a richer social behavior repertoire than
      mice. Uniquely detectable emissions of ultrasonic vocalizations (USV) in rats
      serve as situation-dependent affective signals and accomplish important
      communicative functions. We report, for the first time, a call and response
      acoustic playback assay of bidirectional social communication in juvenile Shank3
      rats. Interestingly, we found that Shank3-deficient null males did not
      demonstrate the enhanced social approach behavior typically exhibited following
      playback of pro-social USV. Concomitantly, we discovered that emission of USV in
      response to playback was not genotype-dependent and emitted response calls were
      divergent in meaning. This is the first report of these socially relevant
      responses using a genetic model of ASD. A comprehensive and empirical analysis of
      vigorous play during juvenile reciprocal social interactions further revealed
      fewer bouts and reduced durations of time spent playing by multiple key
      parameters, including reduced anogenital sniffing and allogrooming. We further
      discovered that male null Shank3-deficient pups emitted fewer isolation-induced
      USV than Shank3 wildtype controls. Postnatal whole brain anatomical phenotyping
      was applied to visualize anatomical substrates that underlie developmental
      phenotypes. The data presented here lend support for the important role of Shank3
      in social communication, the core symptom domain of ASD. By increasing the number
      of in vivo functional outcome measures, we improved the likelihood for
      identifying and moving forward with medical interventions. Autism Res 2018, 11:
      587-601. (c) 2018 International Society for Autism Research, Wiley Periodicals,
      Inc. LAY SUMMARY: Clinically relevant outcomes are required to demonstrate the
      utility of therapeutics. We introduce findings in a rat model, and assess the
      impact of mutations in Shank3, an autism risk gene. We found that males with
      deficient expression of Shank3 did not demonstrate typical responses in a bi
      directional social communication test and that social interaction was lower on
      key parameters. Outcome measures reported herein extend earlier results in mice
      and capture responses to acoustic calls, which is analogous to measuring
      receptive and expressive communication.

PMID- 29377613
TI  - A New Insight into Cross-Sensitivity to Humidity of SnO2 Sensor.
AB  - The efficiency of gas sensors varies enormously from fundamental study to
      practical application. This big gap comes mainly from the complex and
      unpredictable effect of atmospheric environment, especially in humidity. Here,
      the cross-sensitivity to humidity of a SnO2 sensor from local structural and
      lattice evolutions is studied. The sensing response of ethanol is found to be
      efficiently activated by adsorbing trace of water but inhibited as humidity
      increases. By X-ray diffraction, pair distribution function of synchrotron and ab
      initio calculations, the independent effect of water and ethanol on lattice and
      local structure are clearly revealed, which elucidate the intricate sensing
      reactions. The formation of hydrogen bonds and repulsion of ethoxides play key
      roles in the structural distortions, and also in adsorption energies that are
      critical to the sensitive behavior. The results show the sensor performance
      coupled with local structural evolution, which provides a new insight into the
      controversial effects of humidity on SnO2 sensors.

PMID- 29377614
TI  - Quantification, dissipation behavior and risk assessment of ethion in green pea
      by gas chromatography-electron capture detector.
AB  - Residue investigation was carried out to scrutinize the persistence, dissipation
      behavior, half-life, and risk assessment of ethion on green pea fruit by spraying
      ethion at the fruiting stage followed by another application at 10 day intervals.
      The samples were extracted by using a quick, easy, low-cost, effective, rugged,
      and safe method, and the residues of ethion were analyzed by gas chromatography
      with electron capture detection. Here we report a novel, accurate, and cost
      effective gas chromatography method for the determination of average deposits of
      ethion on green pea. The initial deposits were found to be 4.65 mg/kg following
      the application of insecticide. Residues of ethion reached below the detection
      limit of 0.10 mg/kg after 25 days at recommended dosage. The half-life of ethion
      was found to be 4.62 days. For risk assessment studies, the 25th day will be safe
      for consumers for the consumption of green peas. The developed method is simple,
      sensitive, selective, and repeatable and can be extended for ethion-based
      standardization of herbal formulations containing green pea and its use in
      pesticide industries.

PMID- 29377615
TI  - EasyCloneYALI: CRISPR/Cas9-Based Synthetic Toolbox for Engineering of the Yeast
      Yarrowia lipolytica.
AB  - The oleaginous yeast Yarrowia lipolytica is an emerging host for production of
      fatty acid-derived chemicals. To enable rapid iterative metabolic engineering of
      this yeast, there is a need for well-characterized genetic parts and convenient
      and reliable methods for their incorporation into yeast. Here, the EasyCloneYALI
      genetic toolbox, which allows streamlined strain construction with high genome
      editing efficiencies in Y. lipolytica via the CRISPR/Cas9 technology is
      presented. The toolbox allows marker-free integration of gene expression vectors
      into characterized genome sites as well as marker-free deletion of genes with the
      help of CRISPR/Cas9. Genome editing efficiencies above 80% were achieved with
      transformation protocols using non-replicating DNA repair fragments (such as DNA
      oligos). Furthermore, the toolbox includes a set of integrative gene expression
      vectors with prototrophic markers conferring resistance to hygromycin and
      nourseothricin.

PMID- 29377616
TI  - Persistence of hepatocellular carcinoma risk in hepatitis C patients with a
      response to IFN and cirrhosis regression.
AB  - BACKGROUND AND AIM: In patients with HCV-related cirrhosis, a sustained
      virological response may lead to cirrhosis regression. Whether histological
      changes translate into prevention of long-term complications, particularly
      hepatocellular carcinoma is still unknown. This was investigated in a cohort of
      histological cirrhotics who had been prospectively followed-up for 10 years after
      the achievement of a sustained virological response to IFN. METHODS: In all, 38
      sustained virological response cirrhotics who underwent a liver biopsy 5 years
      post-SVR were prospectively followed to assess the impact of cirrhosis regression
      on clinical endpoints. RESULTS: During a follow-up of 86 (30-96) months from
      liver biopsy, no patients developed clinical decompensation, whilst 5 (13%)
      developed hepatocellular carcinoma after 79 (7-88) months. The 8-year cumulative
      probability of hepatocellular carcinoma was 17%, without differences between
      patients with or without cirrhosis regression (19% [95% CI 6%-50%] vs 14% [95% CI
      4%-44%], P = .88). Patients who developed or did not an hepatocellular carcinoma
      had similar rates of residual cirrhosis (P = 1.0), collagen content (P = .48),
      METAVIR activity (P = .34), portal inflammation (P = .06) and steatosis (P =
      .17). At baseline, patients who developed an hepatocellular carcinoma had higher
      gammaGT (HR 1.03, 95% CI 1.00-1.06; P = .014) and glucose (HR 1.02, 95% CI 1.00
      1.02; P = .012) values; moreover, they had increased Forns Score (HR 12.8, 95% CI
      1.14-143.9; P = .039), Lok Index (HR 6.24, 95% CI 1.03-37.6; P = .046) and PLF
      (HR 19.3, 95% CI 1.72-217.6; P = .016) values. One regressor died of lung cancer.
      The 8-year cumulative survival probability was 97%, independently on cirrhosis
      regression (96% vs 100%, P = 1.0) or hepatocellular carcinoma (100% vs 97%, P =
      1.0). CONCLUSIONS: Post-SVR cirrhosis regression does not prevent hepatocellular
      carcinoma occurrence.

PMID- 29377617
TI  - Peroxiredoxin 1, restraining cell migration and invasion, is involved in
      hepatocellular carcinoma recurrence.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is a high-burden disease. Peroxiredoxin
      1 (PRDX1) is a member of the peroxiredoxin family of antioxidant enzymes. The aim
      of this study was to assess the value of PRDX1 for predicting HCC recurrence
      after curative resection and to explore the role of PRDX1 in HCC cell migration
      and invasion. METHODS: Data of patients with HCC who had undergone complete
      resection between 2002 and 2006 were collected. Immunohistochemical detection of
      PRDX1 in HCC tissue and adjacent non-cancerous tissue was conducted. Kaplan-Meier
      survival estimate and log-rank test were used to assess the relationship between
      PRDX1 expression and prognostic significance. HCC cell migration and invasion
      together with the interaction between PRDX1 and ubiquitin C-terminal hydrolase 37
      (UCH37) were studied in vitro. RESULTS: PRDX1 was expressed at lower levels in
      HCC tissues than in adjacent non-cancerous tissues, and PRDX1 was found to be an
      independent risk factor for disease-free survival and overall survival. PRDX1
      restrained cell migration and invasion in vitro. PRDX1 was found to interact with
      UCH37 to affect HCC cell migration and invasion. CONCLUSION: PRDX1 restrains cell
      migration and invasion in HCC cell lines and that may be involved in a UCH37
      relevant pathway, suggesting that PRDX1 may be a new marker for HCC recurrence
      after surgery.

PMID- 29377618
TI  - MiR-339 depresses cell proliferation via directly targeting S-phase kinase
      associated protein 2 mRNA in lung cancer.
AB  - BACKGROUND: S-phase kinase-associated protein 2 (Skp2) takes great part in the
      development of multiple tumors. However, the post-transcriptional modulation
      mechanism of Skp2 remains unclear. Here, we present a new regulatory microRNA of
      Skp2, miR-339, which directly targets Skp2 to inhibit cell proliferation in lung
      cancer. METHODS: The expression of miR-339 or Skp2 in lung cancer samples was
      tested by real time-PCR. The correlation between miR-339 and Skp2 in lung cancer
      samples was analyzed by Pearson's correlation coefficient. The effect of miR-339
      or anti-miR-339 on Skp2 was evaluated by immunoblotting. The luciferase reporter
      gene assay was used to test the targeting of miR-339 on Skp2. 3-(4,5
      Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide and colony formation
      analysis were applied to examine the function of miR-339 targeting Skp2 in lung
      cancer cells. RESULTS: The negative correlation of miR-339 with Skp2 was found in
      clinical human lung cancer tissues. Furthermore, Skp2 expression was obviously
      abated by miR-339 in lung cancer A549 cells. Mechanistically, we used
      bioinformatics to predict that miR-339 could target the 3'-untranslated region of
      Skp2 mRNA. Luciferase reporter gene assay demonstrated that miR-339 could
      decrease the luciferase activities of the 3'-untranslated region vector of Skp2.
      In terms of function, ectopic miR-339 expression significantly suppressed cell
      proliferation in lung cancer. Overexpressed Skp2 accelerated miR-339-bated
      proliferation of lung cancer cells. MiR-339 inhibitor promoted cell proliferation
      in lung cancer, but Skp2 RNA interference reversed miR-339 inhibitor-driven cell
      proliferation. CONCLUSION: MiR-339 targets the 3'-untranslated region of Skp2
      mRNA to depress the proliferation of lung cancer cells.

PMID- 29377619
TI  - Density Functional Theory Mechanistic Study of Boron-Catalyzed N-Alkylation of
      Amines with Formic Acid: Formic Acid Activation by Silylation Reaction.
AB  - New methodology for the alkylation of amines is an intriguing issue in both
      academia and industry. Recently, several groups reported the metal-free B(C6 F5
      )3 -catalyzed N-alkylation of amines, but the mechanistic details of these
      important reactions are unclear. Herein, a computational study was performed to
      elucidate the mechanism of the N-alkylation of amines with formic acid catalyzed
      by the Lewis acid B(C6 F5 )3 in the presence of hydrosilane. We found that the
      reaction started with the activation of formic acid through a novel model. Then,
      the high electrophilicity of the C center of the formic acid unit and the
      nucleophilic character of the amine resulted in a C-N coupling reaction. Finally,
      two sequential silyl-group and H- transfer steps occurred to generate the final
      product. Upon comparing the reaction barrier and the hydrogenation of indole, our
      mechanism is more favorable than that proposed by the group of Yu and Fu.

PMID- 29377620
TI  - Ulcerative telangiectasia on the face and back of a 6-year-old girl with elevated
      antinuclear antibodies.

PMID- 29377621
TI  - Potassium channel dysfunction in neurons and astrocytes in Huntington's disease.
AB  - Huntington's disease (HD) is a late-onset fatal neurodegenerative disease,
      characterized by progressive movement disorders, psychiatric symptoms, and
      cognitive impairment. The cytosine-adenine-guanine (CAG) triplet expansion
      encoding glutamine present in the protein huntingtin (Htt), produces widespread
      neuronal and glial pathology. Mutant huntingtin (mHtt) nuclear aggregates are the
      primary cause of cortical and striatal neuron degeneration, neuronal
      inflammation, apoptosis and eventual cell loss. The precise mechanisms underlying
      the pathogenesis of neurodegeneration in HD remain poorly understood and HD
      patients have no current cure. Potassium channels are widely expressed in most
      cell types. In neurons, they play a crucial role in setting the resting membrane
      potential, mediating the rapid repolarization phase of the action potential and
      controlling sub-threshold oscillations of membrane potentials. In glial cells,
      their major contributions are maintaining the resting membrane potential and
      buffering extracellular K+ . Thus, potassium channels have an essential function
      in both physiological and pathological brain conditions. This review summarizes
      recent progress on potassium channels involved in the pathology of HD by using
      different HD mouse models. Exploring the dysfunction of potassium channels in the
      brain illustrates new approaches for targeting this channel for the treatment of
      HD.

PMID- 29377622
TI  - Influence of Childhood and Adolescent Fat Development on Fat Mass Accrual During
      Emerging Adulthood: A 20-Year Longitudinal Study.
AB  - OBJECTIVE: Fat mass and the prevalence of overweight/obesity (OWO) increase
      during emerging adulthood (EA; 18-25 years). The factors that contribute to the
      transition from having healthy weight to having OWO during EA are understudied.
      This study aimed to identify the independent effect of concurrent physical
      activity (PA) and energy intake (EI) and childhood/adolescent fat accrual, PA,
      and EI on EA fat accrual. METHODS: One hundred twenty-six participants (59 male)
      were measured serially between 1991 and 2011. Measures included age, height,
      weight, total body and trunk fat mass (TBF and TrF, in grams) derived from dual
      energy x-ray absorptiometry, and PA and EI. Composite childhood/adolescent z
      scores were calculated for each participant (average mean z score) for TBF, TrF,
      PA, and EI. Multilevel random-effects models were developed. RESULTS: EA fat
      accrual was predicted by childhood and adolescent TBF and TrF z score (0.30 +/-
      0.05, P < 0.05), respectively, in both sexes. Concurrent PA (-0.06 +/- 0.02, P <
      0.05) was significant in males only. CONCLUSIONS: These results underscore the
      importance of maintaining a lower TBF and TrF during childhood and adolescence,
      and a higher level of PA in order to mitigate TBF and TrF accrual and prevent the
      transition from having healthy weight to having OWO during EA.

PMID- 29377623
TI  - Are oceanic fronts ecotones? Seasonal changes along the subtropical front show
      fronts as bacterioplankton transition zones but not diversity hotspots.
AB  - Ecotones are regarded as diversity hotspots in terrestrial systems, but it is
      unknown if this 'ecotone effect' occurs in the marine environment. Oceanic fronts
      are widespread mesoscale features, present in the boundary between different
      water masses, and are arguably the best potential examples of ecotones in the
      ocean. Here we performed the first seasonal study along an oceanic front,
      combining 16S rRNA gene sequencing coupled with a high spatial resolution
      analysis of the physical properties of the water masses. Using the Subtropical
      Frontal Zone off New Zealand we demonstrate that fronts delimit shifts in
      bacterioplankton community composition between water masses, but that the
      strength of this effect is seasonally dependent. While creating a transition zone
      where physicochemical parameters and bacterioplankton communities get mixed, this
      ecotone does not result in increased diversity. Thus unlike terrestrial ecotones,
      oceanic fronts are boundaries but not hotspots of bacterioplankton diversity in
      the ocean.

PMID- 29377624
TI  - Exploring the Potential Application of Short Non-Coding RNA-Based Genetic
      Circuits in Chinese Hamster Ovary Cells.
AB  - The majority of cell engineering for recombinant protein production to date has
      relied on traditional genetic engineering strategies, such as gene overexpression
      and gene knock-outs, to substantially improve the production capabilities of
      Chinese Hamster Ovary (CHO) cells. However, further improvements in cellular
      productivity or control over product quality is likely to require more
      sophisticated rational approaches to coordinate and balance cellular pathways.
      For these strategies to be implemented, novel molecular tools need to be
      developed to facilitate more refined control of gene expression. Multiple gene
      control strategies are developed over the last decades in the field of synthetic
      biology, including DNA and RNA-based systems, which allows tight and timely
      control over gene expression. microRNAs has received a lot of attention over the
      last decade in the CHO field and are used to engineer and improve CHO cells. In
      this review we focus on microRNA-based gene control systems and discuss their
      potential use as tools rather than targets in order to gain better control over
      gene expression.

PMID- 29377625
TI  - Mild antithrombin deficiency and risk of recurrent venous thromboembolism:
      results from the MEGA follow-up study.
AB  - : Essentials Mild antithrombin deficiency may increase the risk of recurrent
      venous thromboembolism (VTE). In a cohort study, we stratified patients with VTE
      to various cut-off antithrombin levels. A 1.6-3.7-fold increased risk of
      recurrent VTE was observed in the lowest antithrombin categories. Mild
      antithrombin deficiency (activity < 5th percentile of normal) increases recurrent
      VTE risk. SUMMARY: Background Mild antithrombin deficiency (previously defined as
      antithrombin activity below 70% or 80%) has been associated with a 2.4-3.5-fold
      increased risk of recurrent venous thromboembolism (VTE). This finding may have
      implications for duration of antithrombotic therapy in VTE patients with mild
      antithrombin deficiency. Objectives To externally validate whether mild
      antithrombin deficiency is a risk factor for recurrent VTE. Methods In a
      population-based cohort study, patients with a first VTE (n = 2357) were
      stratified according to percentile cut-off antithrombin levels (< 5th [< 87%], 5
      10th [87-92%], > 10th percentile [> 92%]) and functional antithrombin levels (<
      70%, 70-80%, > 80%). Results During a median follow-up of 7.4 years, 361
      recurrent events occurred (incidence rate, 2.5/100 patient-years). We observed an
      increased risk of recurrent VTE in the lowest antithrombin activity category (<
      5th percentile; < 87%) as compared with antithrombin activity that was > 10th
      percentile (> 92%), with an adjusted hazard ratio (HR) of 1.5 (95%CI, 1.0-2.3).
      When analyses were stratified to antithrombin cut-off criteria of< 70% vs.
      patients with antithrombin activity > 80%, the adjusted HR for venous recurrence
      was 3.7 (95% CI, 1.4-9.9). Mild antithrombin deficiency was able to predict
      recurrent VTE over at least 8 years of follow-up and the association remained
      present when the population was stratified to the presence or absence of
      thrombosis risk factors. Restriction analyses, where patients who used
      anticoagulation at time of blood draw and those who reported drinking >= 5
      glasses alcohol daily were excluded, did not materially affect these outcomes.
      Conclusion This study confirms that mild antithrombin deficiency is a risk factor
      for recurrent VTE.

PMID- 29377626
TI  - Tox21 Enricher: Web-based Chemical/Biological Functional Annotation Analysis Tool
      Based on Tox21 Toxicity Screening Platform.
AB  - The US Toxicology Testing in the 21st Century (Tox21) program was established to
      develop more efficient and human-relevant toxicity assessment methods. The Tox21
      program screens >10,000 chemicals using quantitative high-throughput screening
      (qHTS) of assays that measure effects on toxicity pathways. To date, more than 70
      assays have yielded >12 million concentration-response curves. The patterns of
      activity across assays can be used to define similarity between chemicals.
      Assuming chemicals with similar activity profiles have similar toxicological
      properties, we may infer toxicological properties based on its neighbourhood. One
      approach to inference is chemical/biological annotation enrichment analysis.
      Here, we present Tox21 Enricher, a web-based chemical annotation enrichment tool
      for the Tox21 toxicity screening platform. Tox21 Enricher identifies over
      represented chemical/biological annotations among lists of chemicals
      (neighbourhoods), facilitating the identification of the toxicological properties
      and mechanisms in the chemical set.

PMID- 29377627
TI  - Establishment of a CRISPR/Cas9-Mediated Cysltr1 Knockout Mouse Model and iTRAQ
      Based Proteomic Analysis.
AB  - PURPOSE: To clarify the role of Cysteinyl leukotrienes receptor type 1 (CYSLTR1)
      and find the potential predictors of CYSLTR1 antagonists (leukotriene receptor
      antagonists [LTRAs]) responsiveness in vivo. EXPERIMENTAL DESIGN: Cysltr1
      knockout (KO) mouse model is established by the CRISPR/Cas9 system. The phenotype
      of Cysltr1 KO mice are tested by western blotting (WB), histological
      examinations, and experiment of zymosan A-induced peritoneal inflammation. The
      differentially expressed proteins (DEPs) between the Cysltr1 KO and the wild type
      (WT) mice lung tissues are analyzed by the iTRAQ-based proteomic technology. WB
      is used to validate a subset of DEPs. The total nitric oxide (NO) concentration
      in lung tissues are measured. RESULTS: The Cysltr1 KO mice show the decrease of
      vascular permeability in comparison with the WT mice. Our quantitative proteomic
      analysis identified 239 DEPs in total. WB confirms an increased expression of
      protein kinase C-delta (PKC-delta), while N(G),N(G)-dimethylarginine
      dimethylaminohydrolase 1 (DDAH1) and beta-Catenin expression are reduced. The
      total NO concentrations are significantly reduced in lungs from Cysltr1 KO mice.
      CONCLUSIONS AND CLINICAL RELEVANCE: This study not only provides a comprehensive
      dataset on overall protein changes in Cysltr1 KO mice lung tissues, but also
      sheds light on interpreting the description of lower vascular permeability in
      Cysltr1 KO mice.

PMID- 29377628
TI  - Magnetic core micelles as a nanosorbent for the efficient removal and recovery of
      three organophosphorus pesticides from fruit juice and environmental water
      samples.
AB  - Sodium dodecyl sulfate coated amino-functionalized magnetic iron oxide
      nanoparticles were used as an efficient adsorbent for rapid removal and
      preconcentration of three important organophosphorus pesticides, chlorpyrifos,
      diazinon and phosalone, by ultrasound-assisted dispersive magnetic solid-phase
      microextraction. Fabrication of amino-functionalized magnetic nanoparticles was
      certified by characteristic analyses, including Fourier transform infrared
      spectroscopy, thermogravimetric analysis, scanning electron microscopy, and
      transmission electron microscopy. Affecting parameters on the removal efficiency
      were investigated and optimized through half-fractional factorial design and
      Doehlert design, respectively. The analysis of analytes was performed by high
      performance liquid chromatography with ultraviolet detection. Under the optimum
      conditions, extraction recoveries for 20 ng/mL of organophosphorus pesticides
      were in the range of 84-97% with preconcentration factors in the range of 134
      155. Replicating the experiment in above condition for five times gave the
      relative standard deviations <6%. The calibration curves showed high linearity in
      the range of 0.2-700 ng/mL and the limits of detection were in the range of 0.08
      0.13 ng/mL. The proposed method was successfully applied for both removal and
      trace determination of these three organophosphorus pesticides in environmental
      water and fruit juice samples.

PMID- 29377630
TI  - Upregulation of Foreign Body Response in Obese Mice.
AB  - OBJECTIVE: Obesity is a highly prevalent multifactorial metabolic condition in
      which the need for functional bioengineered substitutes (e.g., scaffolds for
      tissue engineering) is likely to occur. However, the adverse foreign body
      response (FBR) that invariably takes place adjacent to implant devices impairing
      their function is poorly characterized in this condition. This study investigated
      the influence of obesity on the host response to a synthetic matrix implanted
      subcutaneously in high-fat-fed obese mice. METHODS: Histological analysis of 14
      day-old implants was performed to identify collagen deposition, capsule
      thickness, fibroblast-like cells, foreign body giant cells, and mast cells. In
      addition, transforming growth factor beta1 (TGF-beta1) levels in the implants and
      serum were determined. RESULTS: All fibrogenic markers (and TGF-beta1 levels)
      increased in the implants of obese mice compared with their nonobese
      counterparts. Particularly relevant was the fibrous capsule thickness in implants
      of obese mice (234.2 +/- 22.1 um vs. 109.2 +/- 13.4 um in implants of nonobese
      animals). CONCLUSIONS: The study results showing that obesity upregulates the
      main features of the FBR induced by subcutaneous implants in mice may be relevant
      in understanding biomaterial integration and performance in this condition. This
      is crucial to the development of strategies to maintain the integrity and
      function of implantable devices.

PMID- 29377631
TI  - A Silk Cranial Fixation System for Neurosurgery.
AB  - Cranial fixation should be safe, reliable, ideally degradable, and produce no
      hazardous residues and no artifacts on neuroimaging. Protein-based fixation
      devices offer an exciting opportunity for this application. Here, the preclinical
      development and in vivo efficacy verification of a silk cranial fixation system
      in functional models are reported by addressing key challenges toward clinical
      use. A comprehensive study on this fixation system in rodent and canine animal
      models for up to 12 months is carried out. The silk fixation system shows a
      superb performance on the long-term stability of the internal structural support
      for cranial flap fixation and bone reconnection and has good magnetic resonance
      imaging compatibility, and tolerability to high dose radiotherapy, underscoring
      the favorable clinical application of this system for neurosurgery compared to
      the current gold standard.

PMID- 29377633
TI  - Constraint-based modelling captures the metabolic versatility of Desulfovibrio
      vulgaris.
AB  - A refined Desulfovibrio vulgaris Hildenborough flux balance analysis (FBA) model
      (iJF744) was developed, incorporating 1016 reactions that include 744 genes and
      951 metabolites. A draft model was first developed through automatic model
      reconstruction using the ModelSeed Server and then curated based on existing
      literature. The curated model was further refined by incorporating three recently
      proposed redox reactions involving the Hdr-Flx and Qmo complexes and a lactate
      dehydrogenase (LdhAB, DVU 3027-3028) indicated by mutation and transcript
      analyses to serve electron transfer reactions central to syntrophic and
      respiratory growth. Eight different variations of this model were evaluated by
      comparing model predictions to experimental data determined for four different
      growth conditions - three for sulfate respiration (with lactate, pyruvate or H2
      /CO2 -acetate) and one for fermentation in syntrophic coculture. The final
      general model supports (i) a role for Hdr-Flx in the oxidation of DsrC and
      ferredoxin, and reduction of NAD+ in a flavin-based electron confurcating
      reaction sequence, (ii) a function of the Qmo complex in receiving electrons from
      the menaquinone pool and potentially from ferredoxin to reduce APS and (iii) a
      reduction of the soluble DsrC by LdhAB and a function of DsrC in electron
      transfer reactions other than sulfite reduction.

PMID- 29377632
TI  - The effects of brain death and ischemia on tolerance induction are organ
      specific.
AB  - We have previously shown that 12 days of high-dose calcineurin inhibition induced
      tolerance in MHC inbred miniature swine receiving MHC-mismatched lung, kidney, or
      co-transplanted heart/kidney allografts. However, if lung grafts were procured
      from donation after brain death (DBD), and transplanted alone, they were rejected
      within 19-45 days. Here, we investigated whether donor brain death with or
      without allograft ischemia would also prevent tolerance induction in kidney or
      heart/kidney recipients. Four kidney recipients treated with 12 days of
      calcineurin inhibition received organs from donors rendered brain dead for 4
      hours. Six heart/kidney recipients also treated with calcineurin inhibition
      received organs from donors rendered brain dead for 4 hours, 8 hours, or 4 hours
      with 4 additional hours of cold storage. In contrast to lung allograft
      recipients, all isolated kidney or heart/kidney recipients that received organs
      from DBD donors achieved long-term survival (>100 days) without histologic
      evidence of rejection. Proinflammatory cytokine gene expression was upregulated
      in lungs and hearts, but not kidney allografts, after brain death. These data
      suggest that the deleterious effects of brain death and ischemia on tolerance
      induction are organ-specific, which has implications for the application of
      tolerance to clinical transplantation.

PMID- 29377634
TI  - In Immunopeptidomics We Need a Sniper Instead of a Shotgun.
AB  - Immunopeptidomics employs the use of mass spectrometry to identify and quantify
      peptides presented on the surface of cells by major histocompatibility complex
      (MHC; human leukocyte antigen [HLA], in humans) molecules, an essential component
      of adaptive immunity. Currently, immunopeptidomics follows the same or similar
      workflows as the more established field of shotgun proteomics, yet inherent
      differences between these two fields create significant drawbacks for the former.
      In this viewpoint, we would like to highlight such technical issues and provide
      suggestions for novel workflows that would increase peptide sequencing coverage,
      depth, and confidence, collectively enhancing the capabilities of the field of
      immunopeptidomics.

PMID- 29377635
TI  - The Effect of Ambient Carbon Dioxide on Anion-Exchange Membrane Fuel Cells.
AB  - Over the past 10 years, there has been a surge of interest in anion-exchange
      membrane fuel cells (AEMFCs) as a potentially lower cost alternative to proton
      exchange membrane fuel cells (PEMFCs). Recent work has shown that AEMFCs achieve
      nearly identical performance to that of state-of-the-art PEMFCs; however, much of
      that data has been collected while feeding CO2 -free air or pure oxygen to the
      cathode. Usually, removing CO2 from the oxidant is done to avoid the detrimental
      effect of CO2 on AEMFC performance, through carbonation, whereby CO2 reacts with
      the OH- anions to form HCO3- and CO32- . In spite of the crucial importance of
      this topic for the future development and commercialization of AEMFCs,
      unfortunately there have been very few investigations devoted to this phenomenon
      and its effects. Much of the data available is widely spread out and there
      currently does not exist a resource that researchers in the field, or those
      looking to enter the field, can use as a reference text that explains the complex
      influence of CO2 and HCO3- /CO32- on all aspects of AEMFC performance. The
      purpose of this Review is to summarize the experimental and theoretical work
      reported to date on the effect of ambient CO2 on AEMFCs. This systematic Review
      aims to create a single comprehensive account of what is known regarding how CO2
      behaves in AEMFCs, to date, as well as identify the most important areas for
      future work in this field.

PMID- 29377638
TI  - Biofluid spectroscopic disease diagnostics: A review on the processes and
      spectral impact of drying.
AB  - The complex patterns observed from evaporated liquid drops have been examined
      extensively over the last 20 years. Complete understanding of drop deposition is
      vital in many medical processes, and one which is essential to the translation of
      biofluid spectroscopic disease diagnostics. The promising use of spectroscopy in
      disease diagnosis has been hindered by the complicated patterns left by dried
      biological fluids which may inhibit the clinical translation of this technology.
      Coffee-ring formation, cracking and gelation patterns have all been observed in
      biofluid drops, and with surface homogeneity being a key element to many
      spectroscopic techniques, experimental issues have been found to arise. A better
      understanding of the fundamental processes involved in a drying droplet could
      allow efficient progression in this research field, and ultimately benefit the
      population with the development of a reliable cancer diagnostic.

PMID- 29377637
TI  - Design of Copper-Based Bimetallic Nanoparticles for Carbon Dioxide Adsorption and
      Activation.
AB  - Cu-based nanoparticles (NPs) are promising candidates for the catalytic
      hydrogenation of CO2 to useful chemicals because of their low cost. However, CO2
      adsorption and activation on Cu is not feasible. In this work we demonstrate a
      computational framework that identifies Cu-based bimetallic NPs able to adsorb
      and activate CO2 based on DFT calculations. We screen a series of heteroatoms on
      Cu-based NPs based on their preference to occupy a surface site on the NP and to
      adsorb and activate CO2 . We revealed two descriptors for CO2 adsorption on the
      bimetallic NPs, the heteroatom (i) local d-band center and (ii)
      electropositivity, which both drive an effective charge transfer from the NP to
      CO2 . We identified the CuZr bimetallic NP as a candidate nanostructure for CO2
      adsorption and showed that although the Zr sites can be oxidized because of their
      high oxophilicity, they are still able to adsorb and activate CO2 strongly.
      Importantly, our computational results are verified by targeted synthesis,
      characterization, and CO2 adsorption experiments that demonstrate that i) Zr
      segregates on the surface of Cu, ii) Zr is oxidized to form a bimetallic mixed
      CuZr oxide catalyst, which iii) can strongly adsorb CO2 , whereas Cu NPs cannot.
      Overall our work highlights the importance of the generation of binding sites on
      a NP surface based on (catalyst) stability and electronic structure properties,
      which can lead to the design of more effective CO2 reduction catalysts.

PMID- 29377636
TI  - Association of early pregnancy body mass index with post-partum weight change
      among African-American women.
AB  - Post-partum weight retention is relatively common and increases the risk for
      future obesity. Women who are overweight or obese prior to pregnancy, or who gain
      excessively during pregnancy, are more likely to retain weight post-partum. Much
      of the existing research is limited by a single post-partum body-weight measure
      and therefore cannot distinguish post-partum weight retention from post-partum
      weight accrual. This study tested the hypothesis that early pregnancy body mass
      index (BMI) is positively associated with post-partum weight change, independent
      of gestational weight gain (GWG) and breastfeeding (BF) among African-American
      women, a demographic group with greater risk for obesity. Healthy African
      American women (n = 32) were weighed at 2 weeks and 3 months post-partum to
      derive post-partum weight change. Data from prenatal care records were retrieved
      to calculate BMI at the first prenatal care visit and GWG. BF status at 2 weeks
      post-partum was self-reported. Early pregnancy BMI was positively associated with
      post-partum weight change (partial r = 0.53, P < 0.005), independent of GWG and
      BF status at 2 weeks post-partum. These results extend the literature by
      suggesting that the association between early pregnancy BMI and post-partum
      weight retention may be at least partially attributable to the accrual of new
      weight during the post-partum period. Future research in a larger and more
      diverse cohort is warranted and should explore potential mechanisms contributing
      to post-partum weight change.

PMID- 29377639
TI  - Polydactyly, postaxial, type B.
AB  - BACKGROUND: Postaxial polydactyly, type B is the most common type of polydactyly.
      The vestigial sixth finger is attached by a narrow neurovascular pedicle to the
      lateral aspect of the hand or foot at the level of the metacarpal-phalangeal
      joint or the metatarsal-phalangeal joint. The occurrence of this type of
      polydactyly varies among racial groups, by sex and sidedness. Postaxial
      polydactyly, type A is a fully developed extra digit on the lateral aspect of the
      hand or foot with a bifid fifth or sixth metacarpal/metatarsal and is much less
      common. METHODS: In a malformations surveillance program, the frequency in racial
      groups, sex ratio and the frequency of other anomalies can be established.
      RESULTS: Five hundred forty-five affected infants were identified from 1972 to
      2012 in the surveillance of 289,365 liveborn and stillborn infants and elective
      terminations because of fetal anomalies detected prenatally. Postaxial
      polydactyly, type B was an isolated anomaly in 95% of the affected newborns.
      There were more affected males than females. Black infants were affected more
      often than White infants: 0.91/100 vs. 0.035/100 infants. The dangling extra
      digit was much more common in the hands than in the feet. CONCLUSIONS: Postaxial
      polydactyly, type B is almost always an isolated, mild malformation with no
      medical significance. Postaxial polydactyly, types B and A occurred in several
      infants, suggesting that either the underlying mutation(s) can cause both types
      of postaxial polydactyly or that some affected infants have more than one
      mutation. Autosomal dominant inheritance with variable expressivity is
      postulated.

PMID- 29377640
TI  - Malformations among infants of mothers with insulin-dependent diabetes: Is there
      a recognizable pattern of abnormalities?
AB  - BACKGROUND: Infants of diabetic mothers have been shown in several studies to
      have an increased frequency of malformations. In previous studies, an increased
      frequency of several specific malformations has been noted, including
      anencephaly, bilateral renal agenesis, and double outlet right ventricle.
      Surveillance, used to identify all malformed infants in a consecutive sample of
      births, can identify a distinctive pattern of malformations among the affected
      infants. METHODS: The infants of insulin-dependent, pregestational diabetic
      mothers were identified in the daily review of the medical records of each
      newborn infant with a malformation and her/his mother's medical record. Infants
      of mothers with gestational diabetes were excluded. The frequency of each
      malformation was compared to that among the malformed infants of nondiabetic
      mothers. RESULTS: One hundred and eighty-three malformed infants of diabetic
      mothers were identified among the 289,365 births. The most notable malformations
      were: neural tube defects (anencephaly, 9%), heart defects (transposition of
      great arteries, 4%), bilateral renal agenesis or dysgenesis (6%), and vertebral
      anomalies (hemivertebrae, 4%). CONCLUSIONS: There was a recognizable pattern of
      malformations and characteristics of infants of diabetic mothers, although there
      was variation in the pattern among affected infants. Some of the malformations in
      the diabetic embryopathy can be identified in prenatal screening by ultrasound.
      More important, their occurrence can be reduced significantly by the mother
      achieving much better control of her diabetes mellitus prior to conception.

PMID- 29377641
TI  - Malformations attributed to the process of vascular disruption.
AB  - BACKGROUND: Several malformations have been attributed to the process of vascular
      disruption. The central hypothesis for this etiology is that blood flow to a
      structure has been altered after that structure had formed normally. The
      decreased blood flow leads to hypoxia, endothelial cell damage, hemorrhage,
      tissue loss, and repair. After recovery, some structures are normal and others
      show either tissue loss or structural abnormalities, such as syndactyly and
      constriction rings. METHODS: The phenotypic features of the 7,020 infants with
      one or more malformations, who were born to women who had always planned to
      deliver at Brigham and Women's Hospital (BWH) between, 1972 and 2012, that is,
      maternal nontransfers, were reviewed. The phenotypes associated with vascular
      disruption, such as the amniotic band syndrome and terminal transverse limb
      defects (TTLD), were identified. RESULTS: One hundred and five fetuses and
      infants had malformations attributed to the process of vascular disruption. Some
      specific causes of the amniotic band limb deformity were identified. TTLD with
      associated small digit-like nubbins occurred at three levels: proximal forearm,
      wrist, and metacarpal-phalangeal joint. Other causes included severe
      hemoglobinopathies and exposures to misoprostol and to prenatal procedures.
      CONCLUSIONS: Malformations attributed to the process of vascular disruption were
      a distinctive entity, among the recognized etiologies. The timing of the
      causative event in the first trimester was established for infants with exposures
      to either the prostaglandin misoprostol or the prenatal diagnosis procedure
      chorionic villus sampling. One challenge is to identify the developmental steps
      in vascular disruption when no causative exposure can be identified.

PMID- 29377642
TI  - Malformations among 289,365 Births Attributed to Mutations with Autosomal
      Dominant and Recessive and X-Linked Inheritance.
AB  - BACKGROUND: The number of malformations attributed to mutations with autosomal or
      X-linked patterns of inheritance has increased steadily since the cataloging
      began in the 1960s. These diagnoses have been based primarily on the pattern of
      phenotypic features among close relatives. A malformations surveillance program
      conducted in consecutive pregnancies can identify both known and "new" hereditary
      disorders. METHODS: The Active Malformations Surveillance Program was carried out
      among 289,365 births over 41 years (1972-2012) at Brigham and Women's Hospital in
      Boston. The findings recorded by examining pediatricians and all consultants were
      reviewed by study clinicians to establish the most likely diagnoses. The findings
      in laboratory testing in the newborn period were reviewed, as well. RESULTS: One
      hundred ninety-six (0.06%) infants among 289,365 births had a malformation or
      malformation syndrome that was attributed to Mendelian inheritance. A total of
      133 (68%) of the hereditary malformations were attributed to autosomal dominant
      inheritance, with 94 (71%) attributed to apparent spontaneous mutations. Forty
      six (23%) were attributed to mutations with autosomal recessive inheritance, 17
      associated with consanguinity. Seventeen (9%) were attributed to X-linked
      inheritance. Fifteen novel familial phenotypes were identified. The family
      histories showed that most (53 to 71%) of the affected infants were born, as a
      surprise, to healthy, unaffected parents. CONCLUSION: It is important for
      clinicians to discuss with surprised healthy parents how they can have an infant
      with an hereditary condition. Future studies, using DNA samples from consecutive
      populations of infants with malformations and whole genome sequencing, will
      identify many more mutations in loci associated with mendelizing phenotypes.
      Birth Defects Research 110:92-97, 2018.(c) 2018 Wiley Periodicals, Inc.

PMID- 29377643
TI  - Causes of Congenital Malformations.
AB  - BACKGROUND: Many different causes of malformations have been established. The
      surveillance of a consecutive population of births, including stillbirths and
      elective terminations of pregnancy because of fetal anomalies, can identify each
      infant with malformations and determine the frequency of the apparent etiologies.
      This report is a sequel to the first such analysis in the first 10 years of this
      Active Malformations Surveillance Program (Nelson and Holmes, ). METHODS: The
      presence of malformations was determined among 289,365 births over 41 years (1972
      2012) at the Brigham and Women's Hospital in Boston. The abnormalities were
      identified from the review of the examination findings of the pediatricians and
      consultants and diagnostic testing for the live-born infants and the autopsies of
      the fetuses in elective terminations and stillbirths. RESULTS: A total of 7020
      (2.4%) infants and fetuses with one or more malformations were identified with
      these apparent etiologies in 26.6%: Mendelian disorders, including infants with
      postaxial polydactyly, type B; chromosome abnormalities; vascular disruption;
      complications of monozygous twinning; and environmental factors. The
      malformations of unknown etiology were a much larger group. CONCLUSION: While
      several causes of malformations have been identified, many remain unexplained.
      Combining the ascertainment in a future surveillance programs with genome
      sequencing and chromosome microarray analysis will increase significantly the
      number of malformations attributed to genetic mechanisms. Birth Defects Research
      110:87-91, 2018.(c) 2018 Wiley Periodicals, Inc.

PMID- 29377644
TI  - The Active Malformations Surveillance Program, Boston in 1972-2012: Methodology
      and demographic characteristics.
AB  - BACKGROUND: Malformations surveillance programs have been carried out in
      consecutive populations of newborn infants at single hospitals, as well as in
      several hospitals in defined populations. A surveillance program begins with the
      review of the findings recorded by the examining pediatrician in each infant's
      medical record. The results of diagnostic tests, consultations, and imaging
      studies are obtained, also, from that infant's medical record. Some malformations
      surveillance programs identify additional malformations over several months, as
      the infants have hospitalizations and additional diagnostic testing. METHODS:
      289,365 infants (liveborn, stillborn, and fetuses in pregnancies terminated
      because of anomalies) were surveyed from 1972 to 2012 at an urban maternity
      center in Boston to identify each infant with one or more malformations. Each
      mother was interviewed to obtain demographic characteristics, results of prenatal
      testing, family history, and information about exposures in pregnancies. Specific
      diagnoses were established by the study geneticists. RESULTS: 7,020 (2.4%) of the
      289,365 infants surveyed had one or more malformations. The etiologies identified
      included chromosome abnormalities, phenotypes attributed to dominant or recessive
      autosomal or X-linked mutations, vascular disruption, environmental factors, and
      complications of twinning. CONCLUSION: The surveillance of a large consecutive
      population of newborn infants, stillbirths, and aborted fetuses can identify with
      high reliability all infants with one or more malformations. This process of
      ascertainment of affected newborns can be used to improve genetic counseling,
      identify "new" phenotypes, and serve as a system for testing new technologies to
      establish more causes of congenital malformations.

PMID- 29377645
TI  - Iniencephaly.
AB  - BACKGROUND: Iniencephaly is a severe developmental abnormality of the
      craniovertebral junction in which the head is retroflexed dramatically. Anatomic
      studies have identified striking changes in the vertebrae and skull: marked
      lordosis of the cervical vertebrae, duplicated cervical vertebrae, irregularly
      fused cervical vertebrae, a widened foramen magnum and a small posterior fossa.
      The affected infant appears to have no neck, as the skin of the face is
      continuous with the chest and the skin of the posterior scalp is continuous with
      the skin of the back. Iniencephaly is considered a rare neural tube defect. The
      frequency has been higher in geographic areas in which the rates of occurrence of
      anencephaly and myelomeningocele were high. Most affected fetuses are either
      stillborn or die soon after birth. However, one affected individual is an adult
      with normal intelligence. METHODS: A malformations surveillance program can
      identify an unselected group of infants with iniencephaly. This approach can
      determine the prevalence rate, the frequency of associated malformations, and the
      occurrence of close relatives with other neural tube defects. RESULTS: Over 41
      years, the surveillance of 289,365 births identified eight fetuses and newborn
      infants with iniencephaly. Five of the eight had either an additional
      encephalocele or a thoracic myelomeningocele. Two of the eight affected infants
      had a sibling or a cousin with anencephaly. CONCLUSION: These findings suggest a
      relationship between the occurrence of iniencephaly and the most common neural
      tube defects, anencephaly and myelomeningocele. Recent experience confirms that
      this complex neural tube defect is not always lethal. Birth Defects Research
      110:128-133, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29377646
TI  - Stillborn Infants: Associated Malformations.
AB  - BACKGROUND: Stillbirth, defined as death of a fetus in utero after 20 weeks of
      gestation, occurs in 1 to 2% of pregnancies in the United States. Many of these
      stillborn infants have associated malformations, including chromosome
      abnormalities, neural tube defects, and malformation syndromes. Other causes are
      abnormalities of the placenta and maternal conditions, such as pre-eclampsia and
      obesity. A consecutive sample of malformed stillborn infants can establish the
      relative frequency and severity of the associated malformations. METHODS:
      Stillbirths were identified in the Active Malformations Surveillance Program at
      Brigham and Women's Hospital (1972-2012). The findings at autopsy, including the
      findings in the placenta and the results of diagnostic studies, were compiled.
      RESULTS: One hundred twenty-seven stillborn infants with malformations were
      identified at autopsy among 289,365 pregnancies, including trisomies 21, 18, and
      13; 45,X; triploidy; anencephaly; lower urinary tract obstruction;
      holoprosencephaly and severe heart defects, such as hypoplastic left heart
      syndrome and tetralogy of Fallot with pulmonary atresia. The severity of the
      abnormalities in stillborn infants was more severe than the spectrum of
      abnormalities identified in live-born infants. CONCLUSION: An autopsy of the
      stillborn fetus, including chromosome microarray and an examination of the
      placenta, can identify the underlying causes of the stillbirth. This review of
      stillborn fetuses with malformations showed that several different lethal
      malformations and heart defects are more common than among live-born infants.
      These postmortem examinations can improve the counseling of the parents about
      risks in future pregnancies. Birth Defects Research 110:114-121, 2018.(c) 2018
      Wiley Periodicals, Inc.

PMID- 29377647
TI  - Cellular Uptake and Tissue Biodistribution of Functionalized Gold Nanoparticles
      and Nanoclusters.
AB  - In this study, the in vitro uptake by fibroblasts and in vivo biodistribution of
      15 nm 11-mercaptoundecanoicacid-protected gold nanoparticles (AuNPs-MUA) and 3 nm
      glutathione- and 3 nm bovine serum albumin-protected gold nanoclusters (AuNCs@GSH
      and AuNCs@BSA, respectively) were evaluated. In vitro cell viability was examined
      after gold nanoparticle treatment for 48 h, based on MTT assays and analyses of
      morphological structure, the cycle cell, cellular doubling time, and the gold
      concentration in cells. No potential toxicity was observed at any studied
      concentration (up to 10 ppm) for AuNCs@GSH and AuNCs@BSA, whereas lower cell
      viability was observed for AuNPs-MUA at 10 ppm than for other treatments. Neither
      morphological damage nor modifications to the cell cycle and doubling time were
      detected after contact with nanoparticles. Associations between cells and AuNPs
      and AuNCs were demonstrated by inductively coupled plasma mass spectrometry (ICP
      MS). AuNCs@GSH exhibited fluorescence emission at 611 nm, whereas AuNCs@BSA
      showed a band at 640 nm. These properties were employed to confirm their
      associations with cells by fluorescence confocal microscopy; both clusters were
      observed in cells and maintained their original fluorescence. In vivo assays were
      performed using 9 male mice treated with 1.70 MUg Au/g body weight gold
      nanoparticles for 24 h. ICP-MS measurements showed a different biodistribution
      for each type of nanoparticle; AuNPs-MUA mainly accumulated in the brain,
      AuNCs@GSH in the kidney, and AuNCs@BSA in the liver and spleen. Spleen indexes
      were not affected by nanoparticle treatment; however, AuNCs@BSA increased the
      thymus index significantly from 1.28 to 1.79, indicating an immune response.
      These nanoparticles have great potential as organ-specific drug carriers and for
      diagnosis, photothermal therapy, and imaging.

PMID- 29377648
TI  - Xerogel Interfaced Nanofibers Stimulate Bone Regeneration Through the Activation
      of Integrin and Bone Morphogenetic Protein Pathways.
AB  - A xerogel was interfaced onto biopolymer nanofibers though a core-shell
      electrospinning design for bone regeneration. The xerogel-interfaced biopolymer
      nanofibrous matrix was bioactive and highly hydrophilic, with a significant
      decrease in the water contact angle. The matrix showed excellent in vitro
      responses of primary osteoblasts in terms of adhesion, proliferation, and
      migration. Furthermore, the osteoblastic differentiation of cells, including
      alkaline phosphatase activity, mineralization, and gene expression, was
      significantly upregulated by the xerogel interface. In vivo animal tests in a
      critical-sized calvarial defect confirmed the new bone formation ability of the
      xerogel-surfaced nanofiber matrices. The underlying signaling mechanisms of the
      stimulation were implied to be integrin and bone morphogenetic protein (BMP)
      pathways, as demonstrated by the activation of integrin (alpha2beta1) and
      downstream signaling molecules (FAK, paxillin, RhoA, MAPK, and NF-kappaB), as
      well as the BMPs and the downstream transcription factor Smad1/5/8. Taking these
      findings together, the xerogel-surfaced biopolymer nanofibers are proposed to be
      a promising scaffold candidate for bone regeneration.

PMID- 29377649
TI  - Development of pH-Sensitive Cationic PEGylated Solid Lipid Nanoparticles for
      Selective Cancer-Targeted Therapy.
AB  - Solid lipid nanoparticles (SLNs) are suitable candidates for the delivery of
      various anti-cancer drugs. However, currently insufficient tumor-permeability and
      non-specific uptake by the reticuloendothelial system limits the application of
      SLNs. Here, we developed novel pH-sensitive cationic polyoxyethylene (PEGylated)
      SLNs (PEG-SLNs+) that could accumulate long-term at various tumor sites to
      enhance the therapeutic efficiency of camptothecin (CPT). These CPT-loaded PEG
      SLNs+ (CPT-PEG-SLNs+) were spherical nanoparticles, with small size (~52.3+/-1.7
      nm), positive charge (~34.3+/-3.5 mV) and high entrapment efficiency (~99.4+/
      1.7%). Drug release profile indicated the overall released amount of CPT from CPT
      PEG-SLNs+ at pH 5.5 was 20.2% more than at pH 7.4, suggesting CPT-PEG-SLNs+ were
      a pH-sensitive SLNs. This PEG-SLNs+ could be efficiently uptaken into cells to
      inhibit the proliferation of CL1-5 cells (IC50 = 0.37 +/-0.21 ug/ml) or HCC36
      cells (IC50 = 0.16+/-0.43 ug/ml). In living animal, our PEG-SLNs+ could
      accumulate long-term (for more than 120 hours) in various types of tumor,
      including human lung carcinoma (NCI-H358, CRL5802, CL1-5), human colon carcinoma
      (HCT-116) and human hepatocellular carcinoma (HCC36), and CPT-PEG-SLNs+ could
      efficiently enhance the therapeutic efficiency of CPT to suppress the growth of
      the HCC36 or CL1-5 tumors. Therefore, Successful development of these pH
      sensitive PEGylated cationic SLNs may provide a selective and efficient drug
      delivery system for cancer therapy.

PMID- 29377650
TI  - Photodynamic Therapy with Liposomal Zinc Phthalocyanine and Tirapazamine
      Increases Tumor Cell Death via DNA Damage.
AB  - The efficacy of photodynamic therapy (PDT) in some solid tumors is limited by the
      poor biodistributive properties of conventional photosensitizers and a natural
      predisposition of tumor cells to survive hypoxia and oxidative stress. This study
      investigated the therapeutic potential of a third-generation photosensitizer,
      liposomal zinc phthalocyanine (ZnPC), in combination with the hypoxic cytotoxin
      tirapazamine (TPZ). TPZ induces DNA double strand breaks (DSBs) under hypoxic
      conditions and subsequent apoptosis via p53 signaling. Experiments were performed
      in tumor cells with functional p53 (Sk-Cha1) and dysfunctional p53 (A431). The
      combination therapy of TPZ and PDT induced DNA DSBs and cell cycle stalling and
      enhanced the cytotoxicity of PDT by exacerbating apopotic and non-apoptotic tumor
      cell death. These phenomena occurred regardless of oxygen tension and the
      mechanism of cell death differed per cell line. Liposomes containing both ZnPC
      and TPZ exhibited no dark toxicity but were more lethal to both cell types after
      PDT compared to ZnPC-liposomes lacking TPZ-an effect that was more pronounced
      under hypoxic conditions. In conclusion, TPZ is a suitable pharmaceutical
      compound to increase PDT efficacy by exploiting the post-PDT tumor hypoxia. The
      inclusion of TPZ and ZnPC into a single liposomal delivery system was feasible.
      The PDT strategy described in this study may be valuable for the treatment of PDT
      recalcitrant tumors.

PMID- 29377653
TI  - Enzyme and Cancer Cell Selectivity of Nanoparticles: Inhibition of 3D Metastatic
      Phenotype and Experimental Melanoma by Zinc Oxide.
AB  - Biomedical applications for metal and metal oxide nanoparticles are rapidly
      increasing. Here their functional impact on two well-characterized model enzymes,
      Luciferase (Luc) or beta-galactosidase (beta-Gal) was quantitatively compared.
      Nickel oxide nanoparticle (NiO-NP) activated beta-Gal (>400% control) and boron
      carbide nanoparticle (B4C-NP) inhibited Luc(<10% control), whereas zinc oxide
      (ZnO-NP) and cobalt oxide (Co3O4-NP) activated beta-Gal to a lesser extent and
      magnesium oxide (MgO) moderately inhibited both enzymes. Melanoma specific
      killing was in the order; ZnO > B4C >= Cu > MgO > Co3O4 > Fe2O3 > NiO, ZnO-NP
      inhibiting B16F10 and A375 cells as well as ERK enzyme (>90%) and several other
      cancer-associated kinases (AKT, CREB, p70S6K). ZnO-NP or nanobelt (NB) serve as
      photoluminescence (PL) cell labels and inhibit 3-D multi-cellular tumor spheroid
      (MCTS) growth and were tested in a mouse melanoma model. These results
      demonstrate nanoparticle and enzyme specific biochemical activity and suggest
      their utility as new tools to explore the important model metastatic foci 3-D
      environment and their chemotherapeutic potential.

PMID- 29377655
TI  - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

PMID- 29377654
TI  - Peptide-Mediated Targeting Mesoporous Silica Nanoparticles: A Novel Tool for
      Fighting Bladder Cancer.
AB  - Transitional cell carcinoma of the bladder is particularly devastating due to its
      high rate of recurrence and difficulty in retention of treatments within the
      bladder. Current cystoscopic approaches to detect and stage the tumor are limited
      by the penetrative depth of the cystoscope light source, and intravesical dyes
      that highlight tumors for surgical resection are non-specific. To address the
      needs for improved specificity in tumor detection and follow-up, we report on a
      novel technology relying on the engineered core of mesoporous silica (MSN) with
      surface modifications that generate contrast in fluorescence and magnetic
      resonance imaging (MRI). The particle surface was further functionalized to
      include a bladder cancer cell specific peptide, Cyc6, identified via phage
      display. This peptide possesses nanomolar specificity for bladder cancer cells
      and homology across multiple species including mouse, canine, and human. Our
      study takes advantage of its target expression in bladder tumor which is not
      expressed in normal bladder wall. When functionalized to MSN, the Cyc6 improved
      binding efficiency and specificity for bladder cancer cells in vitro. In an in
      vivo model, MSN instilled into bladders of tumor-bearing mice enhanced T 1- and T
      2-weighted MRI signals, improving the detection of the tumor boundaries. These
      findings support the notion that our targeted nanomaterial presents new options
      for early detection and eventual therapeutic intervention. Ultimately, the
      combination of real-time and repeated MRI evaluation of the tumors enhanced by
      nanoparticle contrast have the potential for translation into human clinical
      studies for tumor staging, therapeutic monitoring, and drug delivery.

PMID- 29377656
TI  - Toxicological characteristics of the main lipid oxidation products.
AB  - This article gives a brief overview of the available scientific data on the
      toxicity of lipid oxidation products.  The description is logically divided into
      two parts: the toxicity of primary oxidation products (lipid peroxides) and
      toxicity of secondary oxidation products (carbonyl compounds). Mechanisms of
      their toxic effect, indicating the most sensitive target organ, as well as the
      metabolic pathways and main products of their metabolism and half-lethal doses of
      the main products of oxidation are characterized.  It is noted that the most
      toxic products among them are secondary products of lipid oxidation, in
      particular, the acrolein with a half-lethal dose of 7-46 mg per kg body weight. 
      It is concluded that the accent in the control of lipid and lipid containing food
      safety must be shifted to identify specific, the most toxic, secondary lipid
      oxidation products.

PMID- 29377657
TI  - Some aspects of the structure and organization of child nutrition in a number of
      regions Russia.
AB  - This research aims to assess catering arrangements and dietary patterns of
      children at preschool educational institution and at home. The article analyses
      catering arrange-ments for pre-school children (3-7-year-old) from Ekaterinburg,
      Nizhny Tagil, Kamensk-Uralsky, Vladikavkaz and Krasnoyarsk. Based on menu
      production records provided by preschool educational institution, and family
      nutrition questionnaires we have examined their compliance with the nutritional
      physiological standards. The summarized data on menu production records from
      preschool educational institutions showed whether they met food basket
      requirements (net weight), as well as nutritional value requirements (proteins,
      fats, carbohydrates, calories content). The assessment was carried out in
      Ekaterinburg, Nizhny Tagil and Krasnoyarsk using Public catering calculations
      software (version 5) and a proprietary database of childreris food formulae.
      Childrens food basket assess-ment in Ekaterinburg and Kamensk-Uralsky revealed
      underconsumptionof vegetables (17.9-38% decrease), milk (52.7-62% decrease), curd
      (40.2-45.3% decrease). We have also observed decreased consumption of fruits,
      including dried fruit, by 31.8%, as well as cereals and legumes by 43% in Kamensk
      Uralsky. Macronutrient analysis has shown underconsumption of total carbohydrates
      (by 19%) and animal proteins. The assessment of children nutrition at home has
      been carried out using NUTRITEST-IP diagnostic sys-tem in Nizhny Tagil, Kamensk
      Uralsky, Vladikavkaz and Krasnoyarsk. The results showed overconsumption of most
      foods except vegetables. Excessive intake of fats and sugars (3.6 and 3.5 fold
      higher, respectively) accounted for higher than normal energy consump-tion by
      children at home. The evaluation has also revealed a significant difference in
      the consumption of saturated fats, mono - and disaccharides, food fibers and
      vitamin C by the children from the locations included in the study. The excessive
      intake of simple carbohy-drates was typical for family diets and excessive fat
      intake was characteristic for child diet in preschool educational institution.

PMID- 29377658
TI  - Characteristics of the nutrition organization and nutrient consumption in
      toddlers' living in the Central Federal District, Russian Federation (Moscow,
      Ivanovo, Yaroslavl).
AB  - A multicenter cross-sectional study with the participation of 356 healthy
      children aged 1 to 3 years from the cities of the Central Federal District:
      Moscow (n=106), Ivanovo (n=126), Yaroslavl (n=124) has been carried out.
      Questionnaire method, the method of 24-hour diet recall for 3 days (2 weekdays
      and 1 weekend) and the method of diary recording of food intake were used. The
      average daily volumes of food were consistent with the recommended age norms only
      in 31.2% of the surveyed children; after 1 year of life children actively started
      to transfer to nutrition from the family table and only 51.7% of children
      continued to receive individually prepared for baby food. The recommended dietary
      allowances were inadequate in macro- and micronutrients: 48.6% of all children
      received excessive amounts of protein and fat, and 74.1% were less in
      carbohydrates. The consumption of vitamins D and A and minerals (calcium, iron
      and zinc) did not correspond to existing recommendations in the majority of
      cases: only 10-30% of the examined children received physiological norms of
      vitamins from food and 13-34% - some minerals and trace elements. These results
      indicate that the nutrition of young children living in the Central Federal
      District is imbalanced on daily caloric, macro- and micronutrient composition,
      does not fully meet the requirements of the balanced diet and needs serious
      optimization.

PMID- 29377659
TI  - Assessment of efficacy of specialized food products with modified carbohydrate
      profile in patients with type 2 diabetes.
AB  - Objective - To evaluate the effect of diet therapy with the inclusion of
      specialized food product with a modified carbohydrate profile (fruit jelly) on
      glycemic and metabolic parameters in patients with type 2 diabetes mellitus. The
      study included 45 patients (aged 35 to 69 years) with type 2 diabetes with
      concomitant obesity I-III degree. The study was conducted in two stages. The
      first phase evaluated the effect of jelly intake on postprandial glycemia with
      determination of blood glucose levels on an empty stomach and 30, 60, 120 and 180
      minutes after consumption of fruit jelly with maltitol, pectin and sublimated
      raspberry juice and traditional marmalade with fructose (control), containing 25
      g of digestible carbohydrates. In the second phase the effectiveness of
      combination therapy during 2 weeks of the inclusion of fruit jelly with a
      modified carbohydrate profile in a standard hypocaloric diet (1550 kcal/day) has
      been assessed. It has been shown that the dynamics of postprandial glycemia in
      patients with type 2 diabetes after the consumption of fruit jelly with a
      modified carbohydrate profile was comparable to the dynamics of blood glucose
      after eating traditional marmalade with fructose. Inclusion of fruit jelly with a
      modified carbohydrate profile in the standard diet therapy of patients with type
      2 diabetes during 2 weeks was accompanied by positive dynamics of carbohydrate
      and lipid metabolism, as well as a decrease in the content of lipid peroxidation
      products in blood plasma: reducing the level of conjugated dienes and
      malondialdehyde averaged 15.2 and 17.4% from baseline (p<0.05), respectively,
      while content of lipid peroxidation products in blood plasma did not changed in
      patients from the control group.

PMID- 29377660
TI  - Comparative analysis of requirements for quality of fish oil for food and medical
      applications.
AB  - Fish oil is reach natural source of vitamins A, E, D and polyunsaturated fatty
      acids (PUFA) which are useful for supplementation, prophylaxis and therapy in
      food industry, medicine and veterinary. The analysis of regulatory documents for
      the quality of fish oil (based on concentration of main nutrients) leads to
      conclusion that content of vitamins A and D, and PUFA is controlled in medicinal
      preparations. With regard to fish oil for food application there is no unified
      approach. In particularly, content of vitamin D in food supplements with fish oil
      available on Russian market is not indicated by manufacturer or its concentration
      varies in 3-10 folds. Because of important biological functions and
      pharmacological activity, it is very important to have uniform standardization
      for vitamins and PUFA in fish oil for application in food industry and medicine.
      Development and unification of analytical methods became special attention for
      these reasons.

PMID- 29377661
TI  - Cholesterol - an essential component of infant milk formulae?
AB  - It is recognized that breast milk is the ideal food for newborns. Indeed breast
      milk can provide basic guidelines to improve the composition of ingredients in
      adapted infant formulae. One of the main parts of breast milk is milk fat.
      Although the exact functionality of the entire spectrum of fat is not yet fully
      understood, it is known that various lipids present in breast milk, can modulate
      functions of the gastrointestinal tract, the lipoprotein metabolism, the
      structure and function of cell membranes, as well as many signal pathways in the
      infant's organism. In this paper we tried to present evidence that dietary
      cholesterol (CHOL) is a very important component of the infant's nutrition.
      Meanwhile, almost all infant formulae, both cow and goat milk based, use nearly
      only vegetable oils as their fat component providing phytosterols, rather than
      CHOL as in breast milk. It is known that breast milk is a rich source of CHOL and
      phytosterols cannot perform the functions of CHOL. One can imagine that when the
      infant is transferred to artificial feeding with such formulae, and denied the
      opportunity to receive dietary CHOL in any useful amounts, this may affect
      outcomes like optimal child development, and may have a major long-term
      'programming' effect on the metabolism of CHOL. We propose to discuss the thesis
      of the great importance of the presence of CHOL in infant formulae. The applied
      value of this thesis is the need to optimize the fat component of breast milk
      substitutes by introducing CHOL, for example, in the composition of milk fat.
      Although it is clear that compelling evidence of the potential benefits of adding
      various sources of CHOL infant formula is insufficient, at this stage, there is
      cause for a critical discussion and review of the composition of functional
      components of breast milk substitutes.

PMID- 29377662
TI  - Monolayered Silicon and Germanium Monopnictide Semiconductors: Excellent
      Stability, High Absorbance, and Strain Engineering of Electronic Properties.
AB  - The discovery of stable two-dimensional (2D) semiconductors with exotic
      electronic properties is crucial to the future electronic technologies. Using the
      first-principles calculations, we predict the monolayered Silicon- and Germanium
      monopnictides as a new class of semiconductors owning excellent dynamical and
      thermal stabilities, prominent anisotropy, and high possibility of experimental
      exfoliation. These semiconductors, including the monolayered SiP, SiAs, GeP, and
      GeAs, possess wide bandgaps of 2.08-2.64 eV obtained by hybrid functional
      calculation. Under small uniaxial strains (-2 to 3%), dramatic modulations of
      their band structures are observed, and furthermore, all the 2D monolayers (MLs)
      can be transformed between indirect and direct semiconductors. The monolayered
      GeAs and SiP exhibits extraordinary optical absorption in the range of visible
      and ultraviolet (UV) light spectra, respectively. The exfoliation energies of
      these monolayers are comparable to graphene, implying a strong probability of
      successful fabrication by mechanical exfoliation. These intriguing properties of
      the monolayered silicon- and germanium-monopnictides, combined with their highly
      stable structures, offer tremendous opportunities for electronic and
      optoelectronic devices working under UV-visible spectrum.

PMID- 29377664
TI  - The Effect of Oxygen Uptake on Charge Injection Barriers in Conjugated Polymer
      Films.
AB  - The energy offset between the electrode Fermi level and organic semiconductor
      transport levels is a key parameter controlling the charge injection barrier and
      hence efficiency of organic electronic devices. Here, we systematically explore
      the effect of in situ oxygen exposure on energetics in n-type conjugated polymer
      P(NDI2OD-T2) films. The analysis reveals that an interfacial potential step is
      introduced for a series of P(NDI2OD-T2) electrode contacts, causing a nearly
      constant downshift of the vacuum level, while the ionization energies versus
      vacuum level remain constant. These findings are attributed to the establishment
      of a so-called double-dipole step via motion of charged molecules and will modify
      the charge injection barriers at electrode contact. We further demonstrate that
      the same behavior occurs when oxygen interacts with p-type polymer TQ1 films,
      indicating it is possible to be a universal effect for organic semiconductors.

PMID- 29377663
TI  - Characterization of the Fast and Promiscuous Macrocyclase from Plant PCY1 Enables
      the Use of Simple Substrates.
AB  - Cyclic ribosomally derived peptides possess diverse bioactivities and are
      currently of major interest in drug development. However, it can be chemically
      challenging to synthesize these molecules, hindering the diversification and
      testing of cyclic peptide leads. Enzymes used in vitro offer a solution to this;
      however peptide macrocyclization remains the bottleneck. PCY1, involved in the
      biosynthesis of plant orbitides, belongs to the class of prolyl oligopeptidases
      and natively displays substrate promiscuity. PCY1 is a promising candidate for in
      vitro utilization, but its substrates require an 11 to 16 residue C-terminal
      recognition tail. We have characterized PCY1 both kinetically and structurally
      with multiple substrate complexes revealing the molecular basis of recognition
      and catalysis. Using these insights, we have identified a three residue C
      terminal extension that replaces the natural recognition tail permitting PCY1 to
      operate on synthetic substrates. We demonstrate that PCY1 can macrocyclize a
      variety of substrates with this short tail, including unnatural amino acids and
      nonamino acids, highlighting PCY1's potential in biocatalysis.

PMID- 29377665
TI  - S,N-Heteroacene-Based Copolymers for Highly Efficient Organic Field Effect
      Transistors and Organic Solar Cells: Critical Impact of Aromatic Subunits in the
      Ladder pi-System.
AB  - Three novel donor-acceptor alternating polymers containing ladder-type
      pentacyclic heteroacenes (PBo, PBi, and PT) are synthesized, characterized, and
      further applied to organic field effect transistors (OFETs) and polymer solar
      cells. Significant aspects of quinoidal characters, electrochemical properties,
      optical absorption, frontier orbitals, backbone coplanarity, molecular
      orientation, charge carrier mobilities, morphology discrepancies, and the
      corresponding device performances are notably different with various
      heteroarenes. PT exhibits a stronger quinoidal mesomeric structure, linear and
      coplanar conformation, smooth surface morphology, and better bimodal crystalline
      structures, which is beneficial to extend the pi-conjugation and promotes charge
      transport via 3-D transport pathways and in consequence improves overall device
      performances. Organic photovoltaics based on the PT polymer achieve a power
      conversion efficiency of 6.04% along with a high short-circuit current density
      (JSC) of 14.68 mA cm-2, and a high hole mobility of 0.1 cm2 V-1 s-1 is fulfilled
      in an OFET, which is superior to those of its counterparts, PBi and PBo.

PMID- 29377666
TI  - High-Rota Synthesis of Single-/Double-/Multi-Unit-Cell Ti-HSZ Nanosheets To
      Catalyze Epoxidation of Large Cycloalkenes Efficiently.
AB  - This work first reports high-efficiency epoxidation of large cycloalkenes (carbon
      number >= 7) with tert-butyl hydroperoxide (TBHP) over single-/double-/multi-unit
      cell nanosheet-constructed hierarchical zeolite, which is synthesized by one-step
      hydrothermal crystallization using piperidine as the structure-directing agent of
      the microporous structure. The excellent catalytic property of the material is
      ascribed to its unique structural characteristic. Plenty of surface titanols or
      silanols on the surface of MWW nanosheets are beneficial for the formation of
      transition-state intermediates; a large number of intercrystalline mesopores in
      the shell of the material not only facilitate the formation of the intermediate
      for TBHP but also have nearly no hindrance for the diffusion and mass transfer of
      bulky cycloalkene to the above intermediates; the 12-MR side cups penetrating
      into the crystals from the external surface are exposed as much as possible to
      the reaction system because of the single-/double-/multi-unit-cell MWW nanosheet,
      serving as the primary reaction space for the epoxidation of bulky cyclic alkene
      and oxidants and providing enough space for the transition state of Ti-OOtBu and
      bulky cycloalkane. Moreover, an efficient calcination-free catalytic reaction
      regeneration method is developed to overcome the challenge for the recyclability
      of microporous Ti-zeolite in the catalytic epoxidation of bulky cycloalkenes.

PMID- 29377667
TI  - Spectroscopic Characterization of the SEI Layer Formed on Lithium Metal
      Electrodes in Phosphonium Bis(fluorosulfonyl)imide Ionic Liquid Electrolytes.
AB  - The chemical composition of the solid electrolyte interphase (SEI) layer formed
      on the surface of lithium metal electrodes cycled in phosphonium
      bis(fluorosulfonyl)imide ionic liquid (IL) electrolytes are characterized by
      magic angle spinning nuclear magnetic resonance (MAS NMR), X-ray photoelectron
      spectroscopy (XPS), fourier transformed infrared spectroscopy, and
      electrochemical impedance spectroscopy. A multiphase layered structure is
      revealed, which is shown to remain relatively unchanged during extended cycling
      (up to 250 cycles at 1.5 mA.cm-2, 3 mA h.cm-2, 50  degrees C). The main
      components detected by MAS NMR and XPS after several hundreds of cycles are LiF
      and breakdown products from the bis(fluorosulfonyl)imide anion including Li2S.
      Similarities in chemical composition are observed in the case of the dilute (0.5
      mol.kg-1 of Li salt in IL) and the highly concentrated (3.8 mol.kg-1 of Li salt
      in IL) electrolyte during cycling. The concentrated system is found to promote
      the formation of a thicker and more uniform SEI with larger amounts of reduced
      species from the anion. These SEI features are thought to facilitate more stable
      and efficient Li cycling and a reduced tendency for dendrite formation.

PMID- 29377668
TI  - Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target
      Identification in Plasmodium falciparum.
AB  - Diaminoquinazolines represent a privileged scaffold for antimalarial discovery,
      including use as putative Plasmodium histone lysine methyltransferase inhibitors.
      Despite this, robust evidence for their molecular targets is lacking. Here we
      report the design and development of a small-molecule photo-cross-linkable probe
      to investigate the targets of our diaminoquinazoline series. We demonstrate the
      effectiveness of our designed probe for photoaffinity labeling of Plasmodium
      lysates and identify similarities between the target profiles of the probe and
      the representative diaminoquinazoline BIX-01294. Initial pull-down proteomics
      experiments identified 104 proteins from different classes, many of which are
      essential, highlighting the suitability of the developed probe as a valuable tool
      for target identification in Plasmodium falciparum.

PMID- 29377669
TI  - Discovery of Potent Benzocycloalkane Derived Diapophytoene Desaturase Inhibitors
      with an Enhanced Safety Profile for the Treatment of MRSA, VISA, and LRSA
      Infections.
AB  - Blocking the biosynthesis process of staphyloxanthin has emerged as a promising
      antivirulence strategy. Our previous research revealed that diapophytoene
      desaturase was an attractive and druggable target against infections caused by
      pigmented Staphylococcus aureus. Benzocycloalkane-derived compounds were
      effective inhibitors of diapophytoene desaturase but limited by high hERG (human
      Ether-a-go-go Related Gene) inhibition activity. Here, we identified a new type
      of benzo-hepta-containing cycloalkane derivative as diapophytoene desaturase
      inhibitors. Among the fifty-eight analogues, 48 (hERG inhibition activity, half
      maximal inhibitory concentration, IC50, of 16.1 MUM) and 51 (hERG inhibition
      activity, IC50 > 40 MUM) were distinguished for effectively inhibiting the
      pigment production of Staphylococcus aureus Newman and three methicillin
      resistant Staphylococcus aureus strains, and the four strains were highly
      sensitize to hydrogen peroxide killing without a bactericidal growth effect. In
      an in vivo assay, 48 and 51 displayed a comparable effect with linezolid and
      vancomycin in livers and hearts in mice against Staphylococcus aureus Newman and
      a more considerable effect against Mu50 and NRS271 with normal administration.

PMID- 29377670
TI  - Tunable Nonvolatile Memory Behaviors of PCBM-MoS2 2D Nanocomposites through
      Surface Deposition Ratio Control.
AB  - Efficient preparation of single-layer two-dimensional (2D) transition metal
      dichalcogenides, especially molybdenum disulfide (MoS2), offers readily available
      2D surface in nanoscale to template various materials to form nanocomposites with
      van der Waals heterostructures (vdWHs), opening up a new dimension for the design
      of functional electronic and optoelectronic materials and devices. Here, we
      report the tunable memory properties of the facilely prepared [6,6]-phenyl-C61
      butyric acid methyl ester (PCBM)-MoS2 nanocomposites in a conventional diode
      device structure, where the vdWHs dominate the electric characteristics of the
      devices for various memory behaviors depending on different surface deposition
      ratios of PCBM on MoS2 nanosheets. Both nonvolatile WORM and flash memory devices
      have been realized using the new developed PCBM-MoS2 2D composites. Specially,
      the flash characteristic devices show rewritable resistive switching with low
      switching voltages (~2 V), high current on/off ratios (~3 * 102), and superior
      electrical bistability (>104 s). This research, through successfully allocating
      massive vdWHs on the MoS2 surface for organic/inorganic 2D nanocomposites,
      illustrates the great potential of 2D vdWHs in rectifying the electronic
      properties for high-performance memory devices and paves a way for the design of
      promising 2D nanocomposites with electronically active vdWHs for advanced device
      applications.

PMID- 29377671
TI  - Multichannel Charge Transport of a BiVO4/(RGO/WO3)/W18O49 Three-Storey Anode for
      Greatly Enhanced Photoelectrochemical Efficiency.
AB  - Photoelectrochemical (PEC) solar conversion is a green strategy for addressing
      the energy crisis. In this study, a three-storey nanostructure
      BiVO4/(RGO/WO3)/W18O49 was fabricated as a PEC photoanode and demonstrated a
      highly enhanced PEC efficiency. The top and middle storeys are a reduced graphene
      oxide (RGO) layer and WO3 nanorods (NRs) decorated with BiVO4 nanoparticles
      (NPs), respectively. The bottom storey is the W18O49 film grown on a pure W
      substrate. In this novel design, experiments and modeling together demonstrated
      that the RGO layer and WO3 NRs with a fast carrier mobility can serve as
      multichannel pathways, sharing and facilitating electron transport from the BiVO4
      NPs to the W18O49 film. The high conductivity of W18O49 can further enhance the
      charge transfer and retard electron-hole recombination, leading to a highly
      improved PEC efficiency of the BiVO4/WO3 heterojunction. As a result, the as
      fabricated three-storey photoanode covered with FeOOH/NiOOH achieves an
      attractive PEC photocurrent density of 4.66 mA/cm2 at 1.5 V versus Ag/AgCl, which
      illustrates the promising potential of the three-storey hetero-nanostructure in
      future photoconversion applications.

PMID- 29377672
TI  - Molecular Mechanism and Evolution of Nuclear Pre-mRNA and Group II Intron
      Splicing: Insights from Cryo-Electron Microscopy Structures.
AB  - Nuclear pre-mRNA splicing and group II intron self-splicing both proceed by two
      step transesterification reactions via a lariat intron intermediate. Recently
      determined cryo-electron microscopy (cryo-EM) structures of catalytically active
      spliceosomes revealed the RNA-based catalytic core and showed how pre-mRNA
      substrates and reaction products are positioned in the active site. These
      findings highlight a strong structural similarity to the group II intron active
      site, strengthening the notion that group II introns and spliceosomes evolved
      from a common ancestor. Prp8, the largest and most conserved protein in the
      spliceosome, cradles the active site RNA. Prp8 and group II intron maturase have
      a similar domain architecture, suggesting that they also share a common
      evolutionary origin. The interactions between maturase and key group II intron
      RNA elements, such as the exon-binding loop and domains V and VI, are
      recapitulated in the interactions between Prp8 and key elements in the
      spliceosome's catalytic RNA core. Structural comparisons suggest that the
      extensive RNA scaffold of the group II intron was gradually replaced by proteins
      as the spliceosome evolved. A plausible model of spliceosome evolution is
      discussed.

PMID- 29377673
TI  - Minimum Resistance Anisotropy of Epitaxial Graphene on SiC.
AB  - We report on electronic transport measurements in rotational square probe
      configuration in combination with scanning tunneling potentiometry of epitaxial
      graphene monolayers which were fabricated by polymer-assisted sublimation growth
      on SiC substrates. The absence of bilayer graphene on the ultralow step edges of
      below 0.75 nm scrutinized by atomic force microscopy and scanning tunneling
      microscopy result in a not yet observed resistance isotropy of graphene on 4H-
      and 6H-SiC(0001) substrates as low as 2%. We combine microscopic electronic
      properties with nanoscale transport experiments and thereby disentangle the
      underlying microscopic scattering mechanism to explain the remaining resistance
      anisotropy. Eventually, this can be entirely attributed to the resistance and the
      number of substrate steps which induce local scattering. Thereby, our data
      represent the ultimate limit for resistance isotropy of epitaxial graphene on SiC
      for the given miscut of the substrate.

PMID- 29377674
TI  - A Dual-Enzyme-Assisted Three-Dimensional DNA Walking Machine Using T4
      Polynucleotide Kinase as Activators and Application in Polynucleotide Kinase
      Assays.
AB  - T4 polynucleotide kinase (T4 PNK), an intracellular kinase, catalyzes the
      phosphorylation of 5'-hydroxyl termini in nucleic acids and plays a crucial role
      in DNA-related physiological activities. Malfunctioning of PNK is associated with
      the deregulation of many cellular activities and eventually induces a variety of
      human diseases. Herein, we report a smart three-dimensional (3D) DNA walking
      machine using PNK as an effective activator when coupled with the duplex DNA
      nuclease-assisted cleavage reaction. The 3D DNA tracks benefit from high DNA
      loading capacity of gold nanoparticles, and the high efficiency of duplex
      nuclease-mediated cyclic cleavage facilitates the movement of the DNA machine in
      response to T4 PNK. The DNA machine is also applied for the PNK assay based on
      the signal amplification from point to area during the DNA walking process. The
      method achieves an excellent detection limit of 0.0067 U/mL with a linear range
      from 0.01 to 0.3 U/mL and a favorable specificity even in complex serum samples.
      Therefore, the 3D DNA machine shows great potential in biochemical and molecular
      biology studies, drug discovery, and clinic diagnostics.

PMID- 29377675
TI  - Anti-Prion Systems in Yeast and Inositol Polyphosphates.
AB  - The amyloid-based yeast prions are folded in-register parallel beta-sheet
      polymers. Each prion can exist in a wide array of variants, with different
      biological properties resulting from different self-propagating amyloid
      conformations. Yeast has several anti-prion systems, acting in normal cells
      (without protein overexpression or deficiency). Some anti-prion proteins
      partially block prion formation (Ssb1,2p, ribosome-associated Hsp70s); others
      cure a large portion of prion variants that arise [Btn2p, Cur1p, Hsp104 (a
      disaggregase), Siw14p, and Upf1,2,3p, nonsense-mediated decay proteins], and
      others prevent prion-induced pathology (Sis1p, essential cytoplasmic Hsp40).
      Study of the anti-prion activity of Siw14p, a pyrophosphatase specific for 5
      diphosphoinositol pentakisphosphate (5PP-IP5), led to the discovery that inositol
      polyphosphates, signal transduction molecules, are involved in [PSI+] prion
      propagation. Either inositol hexakisphosphate or 5PP-IP4 (or 5PP-IP5) can supply
      a function that is needed by nearly all [PSI+] variants. Because yeast prions are
      informative models for mammalian prion diseases and other amyloidoses, detailed
      examination of the anti-prion systems, some of which have close mammalian
      homologues, will be important for the development of therapeutic measures.

PMID- 29377676
TI  - Insights into the Toxicity of Triclosan to Green Microalga Chlorococcum sp. Using
      Synchrotron-Based Fourier Transform Infrared Spectromicroscopy: Biophysiological
      Analyses and Roles of Environmental Factors.
AB  - This study investigated the toxicity of triclosan to the green microalga
      Chlorococcum sp. under multiple environmental stressors. The interactions between
      triclosan and environmental stressors were explored through full two-way
      factorial, synchrotron-based Fourier transform infrared spectromicroscopy and
      principal component analyses. Phosphorus concentration, pH * phosphorus
      concentration, and temperature * pH * NaCl concentration were the most
      statistically significant factors under triclosan exposure. The variation of
      those factors would have a huge impact on biophysiological performances. It is
      interesting to find Chlorococcum sp. may become more resistant against triclosan
      in phosphorus-enriched environment. Besides, particular significant factors from
      multiple environmental stressors showed the impacts of triclosan on the
      corresponding response of Chlorococcum sp. owing to the specific structure and
      performance of biomolecular components. Moreover, two high-order interactions of
      temperature * pH * NaCl concentration and temperature * pH * NaCl concentration *
      phosphorus concentration had more contributions than others at the subcellular
      level, which could be attributed to the interactive complexity of biomolecular
      components. Due to cellular self-regulation mechanism and short exposure time,
      the biophysiological changes of Chlorococcum sp. were undramatic. These findings
      can help reveal the interactive complexity among triclosan and multiple
      environmental stressors. It is suggested that multiple environmental stressors
      should be considered during ecological risk assessment and management of emerging
      pollutants.

PMID- 29377677
TI  - Methane Bubble Growth and Migration in Aquatic Sediments Observed by X-ray MUCT.
AB  - Methane bubble formation and transport is an important component of
      biogeochemical carbon cycling in aquatic sediments. To improve understanding of
      how sediment mechanical properties influence bubble growth and transport in
      freshwater sediments, a 20-day laboratory incubation experiment using homogenized
      natural clay and sand was performed. Methane bubble development at high
      resolution was characterized by MUCT. Initially, capillary invasion by
      microbubbles (<0.1 mm) dominated bubble formation, with continued gas production
      (4 days for clay; 8 days for sand), large bubbles formed by deforming the
      surrounding sediment, leading to enhanced of macropore connectivity in both
      sediments. Growth of large bubbles (>1 mm) was possible in low shear yield
      strength sediments (<100 Pa), where excess gas pressure was sufficient to
      displace the sediment. Lower within the sand, higher shear yield strength (>360
      Pa) resulted in a predominance of microbubbles where the required capillary entry
      pressure was low. Enhanced bubble migration, triggered by a controlled reduction
      in hydrostatic head, was observed throughout the clay column, while in sand
      mobile bubbles were restricted to the upper 6 cm. The observed macropore network
      was the dominant path for bubble movement and release in both sediments.

PMID- 29377678
TI  - Microporous Lead-Organic Framework for Selective CO2 Adsorption and Heterogeneous
      Catalysis.
AB  - A novel microporous metal-organic framework, {[Pb4(MU8-MTB)2(H2O)4].5DMF.H2O}n
      (1; MTB = methanetetrabenzoate and DMF = N,N'-dimethylformamide), was
      successfully synthesized by a solvothermal reaction and structurally
      characterized by single-crystal X-ray diffraction. The framework exhibits a
      unique tetranuclear [Pb4(MU3-COO)(MU2-COO)6(COO)(H2O)4] secondary building unit
      (SBU). The combination of the SBU with the tetrahedral symmetry of MTB results in
      a three-dimensional network structure, with one-dimensional jarlike cavities
      having sizes of about 14.98 * 7.88 and 14.98 * 13.17 A2 and propagating along the
      c axis. Due to the presence of four coordinately unsaturated sites per one metal
      cluster, an activated form of compound 1 (i.e., desolvated form denoted as 1')
      was tested in gas adsorption and catalytic experiments. The studies of gas
      sorption revealed that 1' exhibits a surface area (Brunauer-Emmett-Teller) of 980
      m2.g-1. This value is the highest reported for any compound from the MTB group.
      Interactions of carbon dioxide (CO2) molecules with the framework, confirmed by
      density functional theory calculations, resulted in high CO2 uptake and
      significant selectivity of CO2 adsorption with respect to methane (CH4) and
      dinitrogen (N2) when measured from atmospheric pressure to 21 bar. The high
      selectivity of CO2 over N2 is mostly important for capturing CO2 from the
      atmosphere in attempts to decrease the greenhouse effect. Moreover, compound 1'
      was tested as a heterogeneous catalyst in Knoevenagel condensation of active
      methylene compounds with aldehydes. Excellent catalytic conversion and
      selectivity in the condensation of benzaldehyde and cyclohexanecarbaldehyde with
      malononitrile was observed, which suggests that accessible lead(II) sites play an
      important role in the heterogeneous catalytic process.

PMID- 29377679
TI  - Dithienopicenocarbazole-Based Acceptors for Efficient Organic Solar Cells with
      Optoelectronic Response Over 1000 nm and an Extremely Low Energy Loss.
AB  - Two cheliform non-fullerene acceptors, DTPC-IC and DTPC-DFIC, based on a highly
      electron-rich core, dithienopicenocarbazole (DTPC), are synthesized, showing
      ultra-narrow bandgaps (as low as 1.21 eV). The two-dimensional nitrogen
      containing conjugated DTPC possesses strong electron-donating capability, which
      induces intense intramolecular charge transfer and intermolecular pi-pi stacking
      in derived acceptors. The solar cell based on DTPC-DFIC and a spectrally
      complementary polymer donor, PTB7-Th, showed a high power conversion efficiency
      of 10.21% and an extremely low energy loss of 0.45 eV, which is the lowest among
      reported efficient OSCs.

PMID- 29377680
TI  - Controlled Formation and Binding Selectivity of Discrete Oligo(methyl
      methacrylate) Stereocomplexes.
AB  - The triple-helix stereocomplex of poly(methyl methacrylate) (PMMA) is a unique
      example of a multistranded synthetic helix that has significant utility and
      promise in materials science and nanotechnology. To gain a fundamental
      understanding of the underlying assembly process, discrete stereoregular oligomer
      libraries were prepared by combining stereospecific polymerization techniques
      with automated flash chromatography purification. Stereocomplex assembly of these
      discrete building blocks enabled the identification of (1) the minimum degree of
      polymerization required for the stereocomplex formation and (2) the dependence of
      the helix crystallization mode on the length of assembling precursors. More
      significantly, our experiments resolved binding selectivity between helical
      strands with similar molecular weights. This presents new opportunities for the
      development of next-generation polymeric materials based on a triple-helix motif.

PMID- 29377681
TI  - Correction to Implementation of Constrained DFT for Computing Charge Transfer
      Rates within the Projector Augmented Wave Method.

PMID- 29377682
TI  - Total Synthesis of a Densely Functionalized Plesiomonas shigelloides Serotype 51
      Aminoglycoside Trisaccharide Antigen.
AB  - Plesiomonas shigelloides, a pathogen responsible for frequent outbreaks of severe
      travelers' diarrhea, causes grave extraintestinal infections. Sepsis and
      meningitis due to P. shigelloides are associated with a high mortality rate as
      antibiotic resistance increases and vaccines are not available. Carbohydrate
      antigens expressed by pathogens are often structurally unique and are targets for
      developing vaccines and diagnostics. Here, we report a total synthesis of the
      highly functionalized trisaccharide repeating unit 2 from P. shigelloides
      serotype 51 from three monosaccharides. A judicious choice of building blocks and
      reaction conditions allowed for the four amino groups adorning the sugar rings to
      be installed with two N-acetyl (Ac) groups, rare acetamidino (Am), and d-3
      hydroxybutyryl (Hb) groups. The strategy for the differentiation of amino groups
      in trisaccharide 2 will serve well for the syntheses of other complex glycans.

PMID- 29377683
TI  - Lewis Base/Copper Cooperatively Catalyzed Asymmetric alpha-Amination of Esters
      with Diaziridinone.
AB  - An enantioselective alpha-amination of esters by a Lewis base/copper(I)
      cooperative catalysis strategy has been developed. The transient chiral C1
      ammonium enolate generated from pentafluorophenyl ester and nucleophilic Lewis
      base is nicely compatible with the copper intermediate formed from N, N-di- t
      butyldiaziridinone and Cu(I) to allow for high levels of stereochemical control.
      The cooperative catalytic reaction leads to a diverse set of highly
      enantioenriched hydantoins in good yields with excellent enantioselectivities (90
      99% ee).

PMID- 29377684
TI  - A General Strategy for Site-Selective Incorporation of Deuterium and Tritium into
      Pyridines, Diazines, and Pharmaceuticals.
AB  - Methods to incorporate deuterium and tritium atoms into organic molecules are
      valuable for medicinal chemistry. The prevalence of pyridines and diazines in
      pharmaceuticals means that new ways to label these heterocycles will present
      opportunities in drug design and facilitate absorption, distribution, metabolism,
      and excretion (ADME) studies. A broadly applicable protocol is presented wherein
      pyridines, diazines, and pharmaceuticals are converted into heterocyclic
      phosphonium salts and then isotopically labeled. The isotopes are incorporated in
      high yields and, in general, with exclusive regioselectivity.

PMID- 29377685
TI  - Plant Response to Metal-Containing Engineered Nanomaterials: An Omics-Based
      Perspective.
AB  - The increasing use of engineered nanomaterials (ENMs) raises questions regarding
      their environmental impact. Improving the level of understanding of the genetic
      and molecular basis of the response to ENM exposure in biota is necessary to
      accurately assess the true risk to sensitive receptors. The aim of this Review is
      to compare the plant response to several metal-based ENMs widely used, such as
      quantum dots, metal oxides, and silver nanoparticles (NPs), integrating available
      "omics" data (transcriptomics, miRNAs, and proteomics). Although there is
      evidence that ENMs can release their metal components into the environment, the
      mechanistic basis of both ENM toxicity and tolerance is often distinct from that
      of metal ions and bulk materials. We show that the mechanisms of plant defense
      against ENM stress include the modification of root architecture, involvement of
      specific phytohormone signaling pathways, and activation of antioxidant
      mechanisms. A critical meta-analysis allowed us to identify relevant genes,
      miRNAs, and proteins involved in the response to ENMs and will further allow a
      mechanistic understanding of plant-ENM interactions.

PMID- 29377686
TI  - Interlocked Supramolecular Polymers Created by Combination of Halogen- and
      Hydrogen-Bonding Interactions through Anion-Template Self-Assembly.
AB  - We present the synthesis and oxoanion-assembling properties of a monomer with a
      naphthalene ring as a central core decorated with two arms containing
      iodotriazolium rings as anion binding sites. Interactions with SO42-, H2PO4-, and
      HP2O73- anions, via a cooperative mechanism, afforded new supramolecular
      materials stabilized by a combination of halogen- and hydrogen-bonding
      interactions. 1H NMR experiments and solid-state structure provided evidence for
      the initial formation of a supramolecular linear chain, nucleation step, and then
      two different supramolecular chains are interpenetrated with each other,
      elongation steps, involving the formation of hydrogen bonds between two oxygens
      of the anion from one of the chains and the naphthalene inner protons from the
      other chain. Scanning electron microscopy studies revealed that the morphology of
      the crystals changed dramatically with the nature of the anion added.

PMID- 29377687
TI  - Asymmetric Synthesis of Chiral Primary Amines by Ruthenium-Catalyzed Direct
      Reductive Amination of Alkyl Aryl Ketones with Ammonium Salts and Molecular H2.
AB  - A ruthenium/C3-TunePhos catalytic system has been identified for highly efficient
      direct reductive amination of simple ketones. The strategy makes use of ammonium
      acetate as the amine source and H2 as the reductant and is a user-friendly and
      operatively simple access to industrially relevant primary amines. Excellent
      enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl
      aryl ketones. The practicability of this methodology has been highlighted by
      scalable synthesis of key intermediates of three drug molecules. Moreover, an
      improved synthetic route to the optimal diphosphine ligand C3-TunePhos is also
      presented.

PMID- 29377689
TI  - Chiral Phosphoric Acid Catalyzed Enantioselective Ring Expansion Reaction of 1,3
      Dithiane Derivatives: Case Study of the Nature of Ion-Pairing Interaction.
AB  - Chiral counterion controlled asymmetric catalysis via an ion-pairing interaction
      has attracted immense attention in recent years. Despite a number of successful
      studies, the mechanistic elucidation of the stereocontrolling element in the ion
      pairing interaction is rarely conducted and hence its nature is still far from
      being well understood. Herein we report an in-depth mechanistic case study of a
      newly developed enantioselective ring expansion reaction of 1,3-dithiane
      derivatives catalyzed by chiral phosphoric acid (CPA). An unprecedented
      enantioselective 1,2-sulfur rearrangement/stereospecific nucleophilic addition
      sequence was proven to be the stereoselective pathway. More importantly, by
      thorough investigation of the intrinsic nature of the stereospecific nucleophilic
      addition to the cationic thionium intermediate, we discovered that the key
      interaction in this process is the nonclassical C-H...O hydrogen bonds formed
      between the conjugate base of the CPA catalyst and the cationic intermediate.
      These C-H...O hydrogen bonds not only bind the catalyst to the substrates to form
      energetically favored states throughout the overall processes but also firmly
      maintain the relative positions of these fragments as the "fixed" contact ion
      pair to sustain the chiral information generated at the initial sulfur
      rearrangement step. This mechanistic case study provides a very clear
      understanding of the nature of the ion-pairing interaction in organocatalysis.
      The conclusion encourages the further development of the research field with the
      focus to design new organocatalysts and cultivate novel organocatalytic
      transformations.

PMID- 29377690
TI  - Synthesis of a Cyclophane Bearing Two Benz[a]anthracene Units Connected at the 5
      and 7 Positions with Two Naphth-1,4-diyl Groups.
AB  - A synthetic pathway to a cyclophane bearing two benz[a]anthracene units connected
      at the 5 and 7 positions through two naphth-1,4-diyl groups was developed, and
      its structure was confirmed by X-ray structure analysis. Because of structural
      constraints, the two naphthyl groups are distorted from planarity and the bonds
      connecting them to the benz[a]anthracene units are bent significantly. The UV-vis
      and fluorescence spectra of the cyclophane are red-shifted from those of 7-(1
      naphthalenyl)benz[a]anthracene, which is the corresponding monomeric polycyclic
      aromatic hydrocarbon.

PMID- 29377688
TI  - Enzymatic Self-Assembly Confers Exceptionally Strong Synergism with NF-kappaB
      Targeting for Selective Necroptosis of Cancer Cells.
AB  - As a promising molecular process for selectively inhibiting cancer cells without
      inducing acquired drug resistance, enzyme-instructed self-assembly (EISA) usually
      requires relatively high dosages. Despite its discovery 30 years ago, the
      translation of the knowledge about NF-kappaB signaling into clinic remains
      complicated due to the broad roles of NF-kappaB in cellular regulation. Here we
      show that integrating EISA and NF-kappaB targeting boosts the efficacy of EISA
      over an order of magnitude without compromising selectivity against cancer cells.
      That is, in situ enzymatic self-assembly of a tetrapeptide results in nanofibers,
      which hardly affect cell viability, but lead to inductive expression of tumor
      necrosis factor receptor 2 (TNFR2) and decreased expression of three key proteins
      at the upstream of NF-kappaB pathway in the cancer cells. Adding the inhibitors
      targeting NF-kappaB further decreases the expressions of those upstream proteins,
      which turns the otherwise innocuous nanofibers to being lethal to the cancer
      cells, likely causing necroptosis. As the first case of using supramolecular
      processes to enable synthetic lethality, this work illustrates a versatile
      approach to translate key regulatory circuits into promising therapeutic targets.

PMID- 29377691
TI  - Identification of a Novel Hybridization from Isosorbide 5-Mononitrate and
      Bardoxolone Methyl with Dual Activities of Pulmonary Vasodilation and Vascular
      Remodeling Inhibition on Pulmonary Arterial Hypertension Rats.
AB  - Given the clinical therapeutic efficacy of oral-dosed bardoxolone methyl (1) and
      the selective vasodilatory effect caused by inhalation of nitric oxide (NO) on
      pulmonary arterial hypertension (PAH) patients, a new hybrid (CDDO-NO, 2) from 1
      and NO donor isosorbide 5-mononitrate (3) was designed and synthesized. This
      hybrid could liberate 1 and NO in the lungs of rats after trachea injection.
      Significantly, 2 lowered mean pulmonary artery pressure (mPAP) and right
      ventricular systolic pressure (RVSP), decreased right ventricular hypertrophy
      (RVH), and attenuated pulmonary artery medial thickness (PAMT) and vascular
      muscularization in monocrotaline (MCT)-induced PAH rats. Meanwhile, 2 inhibited
      overproliferation of perivascular cells and diminished macrophage infiltration
      and oxidative stress by inactivation of NOX4. In addition, 2 markedly reduced
      cardiac hypertrophy and fibrosis in the PAH rats. Overall, 2 exhibited potent
      dual activities of pulmonary vasodilation and vascular remodeling inhibition,
      suggesting that it may be a promising agent for PAH intervention.

PMID- 29377692
TI  - Synthesis of Highly Functionalized Indoles and Indolones via Selectivity
      Switchable Olefinations.
AB  - Highly functionalized indoles and indolones were prepared via selectivity
      switchable mono- or diolefinations. The Julia olefination of the products
      followed by a Bronsted acid-prompted cyclization afforded indolones, whereas the
      indoles were obtained by a sequential Wittig olefination and electrocyclization.
      This method opens divergent access to highly functionalized nitrogen-containing
      bicyclic or tricyclic heterocycles.

PMID- 29377694
TI  - Copper-Catalyzed Aerobic Oxidative Reaction of C60 with Aliphatic Primary Amines
      and CS2.
AB  - A novel type of fullerene derivatives, [60]fullerothiazolidinethiones (2), were
      obtained from the copper-catalyzed aerobic oxidative reaction of C60 with
      aliphatic primary amines and CS2 in 4:1 v/v DMF and o-DCB. The obtained products
      were fully characterized with the X-ray single-crystal diffraction and
      spectroscopic methods. Control experiment with maleic anhydride, an analogue to
      C60, also afforded thiazolidinethione product, but via a mechanism different from
      that of C60 judging from the structure difference between the two types of
      thiazolidinethione compounds, demonstrating the unique reactivity of C60.

PMID- 29377693
TI  - Antibodies as Carrier Molecules: Encapsulating Anti-Inflammatory Drugs inside
      Herceptine.
AB  - The human epidermal growth factor receptor 2 (HER2) is overexpressed in about a
      third of breast cancer patients, with a strong involvement of the cyclooxygenase
      2 (COX-2) enzyme in the tumor progress. HER2 and COX-2 are consequently potential
      targets for inhibiting carcionogenesis. Herceptin (trastuzumab) is an antibody
      that partially blocks HER2-positive cancers at their initial stage.
      Unfortunately, the overall response rate to the single treatment with this
      antibody is still modest, and therefore, it needs to be improved by combining
      several chemotherapeutic agents. On the other hand, nonsteroidal anti
      inflammatory drugs (NSAIDs) are designed to halt COX-2 functionality, so they
      might also exhort an anticancer activity. In this contribution, dual Herceptin
      NSAID drugs are designed using theoretical tools. More specifically, blind
      docking, molecular dynamics, and quantum calculations are performed to assess the
      stability of 14 NSAIDs embedded inside Herceptin. Our calculations reveal the
      feasibility of improving the antitumor activity of the parent Herceptin by
      designing a dual HER2-targeting with Etofenamate. That coupling mode might be
      used to further rationalize new clinical strategies beyond classical antibody
      dosages.

PMID- 29377695
TI  - Control of Geminate Recombination by the Material Composition and Processing
      Conditions in Novel Polymer: Nonfullerene Acceptor Photovoltaic Devices.
AB  - Herein, we report on the charge dynamics of photovoltaic devices based on two
      novel small-molecule nonfullerene acceptors featuring a central ketone unit.
      Using ultrafast near-infrared spectroscopy with optical and photocurrent
      detection methods, we identify one of the key loss channels in the devices as
      geminate recombination (GR) of interfacial charge transfer states (CTSs). We find
      that the magnitude of GR is highly sensitive to the choice of solvent and
      annealing conditions. Interestingly, regardless of these processing conditions,
      the same lifetime for GR (~130 ps) is obtained by both detection methods upon
      decomposing the complex broadband transient optical spectra, suggesting this time
      scale is inherent and independent of morphology. These observations suggest that
      the CTSs in the studied material blends are mostly strongly bound, and that
      charge generation from these states is highly inefficient. We further rationalize
      our results by considering the impact of the processing on the morphology of the
      mixed donor and acceptor domains and discuss the potential consequences of the
      early charge dynamics on the performance of emerging nonfullerene photovoltaic
      devices. Our results demonstrate that careful choice of processing conditions
      enables enhanced exciton harvesting and suppression of GR by more than 3 orders
      of magnitude.

PMID- 29377696
TI  - [Evaluation of the role of Campylobacter spp. in the occurrence of foodborne
      diseases and modern methods to detect the pathogen].
AB  - Infections caused by Campylobacter spp. are now considered to be one of the most
      important foodborne diseases worldwide, this organism is one of the most
      epidemiologically significant zoonotic pathogens. Among these pathogens
      Campylobacter jejuni have the greatest epidemiological importance, they are
      responsible for 90% of laboratory confirmed cases of food campylobacteriosis.The
      frequency of detection of campylobacters in the environmental and on many raw
      foods, of both plant and animal origin, in normal intestine biota of domestic and
      wild animal and birds, indicates the prevalence of these bacteria and the high
      risk of contamination of food and water. The main factors of transmission in
      sporadic campylobacteriosis are the poultry and poultry products (up to 70% of
      the total number of cases), water (8%), raw milk (5%). One of the risk factors
      for the spread of emergent pathogen is its ability to persist in aquatic
      ecosystems. Continuing changes in landscape and agricultural intensification can
      cause further enhance microbial contamination of freshwater bodies and
      groundwater, and the associated increase in the number of cases of waterborne
      campylobacteriosis. Intensification of agriculture, expanding the range of
      applied disinfectants and antiseptics, uncontrolled use of antibiotics in
      livestock often leads to the selection of the sustainable strains of
      Campylobacter spp., which have antibiotic resistance and multiple virulence
      determinants.This paper presents an overview of modern methods for the detection
      of Campylobacter spp., detailed culture and biochemical methods for the isolation
      of C. jejuni based on the use of selective culture media and diagnostic kits for
      the characterization of the phenotypic profiles of the strains. These methods are
      the starting point in selecting the most effective schemes of food control and
      surveillance. It is emphasized that the basis of microbiological analysis should
      be molecular methods based on real-time PCR, which allows to quantify present in
      foods of thermotolerant Campylobacter, including C. jejuni.

PMID- 29377697
TI  - Molecular Modeling Analysis of CO2 Absorption by Glymes.
AB  - The properties of diglyme + CO2 systems were analyzed through density functional
      theory and molecular dynamics methods with the objective of inferring the
      microscopic properties of CO2 capture by glyme-based solvents and the effect of
      ether group regarding solvents affinity toward CO2. Calculations of diglyme + CO2
      molecular clusters using density functional theory allowed accurate
      quantification and characterization of short-range intermolecular forces between
      these molecules, whereas the molecular dynamics simulation of diglyme + CO2
      liquid mixtures, for different CO2 contents, were the means to infer the
      properties and dynamics of bulk liquid phases upon CO2 absorption. Likewise,
      liquid diglyme + CO2 gas interfaces were also studied using molecular dynamics
      methods to examine the kinetics of CO2 capture, adsorption at the gas-liquid
      interface, and the mechanism of interface crossing, which is of pivotal
      importance for the design of CO2 capturing units.

PMID- 29377698
TI  - Photoinduced Bimolecular Electron Transfer in Ionic Liquids: Cationic Electron
      Donors.
AB  - Recently, we have reported a systematic study of photoinduced electron-transfer
      reactions in ionic liquid solvents using neutral and anionic electron donors and
      a series of cyano-substituted anthracene acceptors [ Wu , B. ; Maroncelli , M. ;
      Castner , E. W. Jr Photoinduced Bimolecular Electron Transfer in Ionic Liquids .
      J. Am. Chem. Soc. 139 , 2017 , 14568 ]. Herein, we report complementary results
      for a cationic class of 1-alkyl-4-dimethylaminopyridinium electron donors.
      Reductive quenching of cyano-substituted anthracene fluorophores by these
      cationic quenchers is studied in solutions of acetonitrile and the ionic liquid 1
      ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. Varying the length
      of the alkyl chain permits tuning of the quencher diffusivities in solution. The
      observed quenching kinetics are interpreted using a diffusion-reaction analysis.
      Together with results from the prior study, these results show that the intrinsic
      electron-transfer rate constant does not depend on the quencher charge in this
      family of reactions.

PMID- 29377699
TI  - Dependence of the Substituent Effect on Solvent Properties.
AB  - The influence of a solvent on the substituent effect (SE) in 1,4-disubstituted
      derivatives of benzene (BEN), cyclohexa-1,3-diene (CHD), and bicyclo[2.2.2]octane
      (BCO) is studied by the use of polarizable continuum model method. In all X-R-Y
      systems for the functional group Y (NO2, COOH, OH, and NH2), the following
      substituents X have been chosen: NO2, CHO, H, OH, and NH2. The substituent effect
      is characterized by the charge of the substituent active region (cSAR(X)),
      substituent effect stabilization energy (SESE), and substituent constants sigma
      or F descriptors, the functional groups by cSAR(Y), whereas pi-electron
      delocalization of transmitting moieties (BEN and CHD) is characterized by a
      geometry-based index, harmonic oscillator model of aromaticity. All computations
      were carried out by means of B3LYP/6-311++G(d,p) method. An application of
      quantum chemistry SE models (cSAR and SESE) allows to compare the SE in water
      solutions and in the gas phase. Results of performed analyses indicate an
      enhancement of the SE by water. The obtained Hammett-type relationships document
      different nature of interactions between Y and X in aromatic and olefinic systems
      (a coexistence of resonance and inductive effects) than in saturated ones (only
      the inductive effect). An increase of electric permittivity clearly enhances
      communications between X and Y for BEN and CHD systems.

PMID- 29377700
TI  - Interlayer Trions in the MoS2/WS2 van der Waals Heterostructure.
AB  - Electronic excitations in van der Waals heterostructures can have interlayer or
      intralayer character depending on the spatial localization of the involved
      charges (electrons and holes). In the case of neutral electron-hole pairs
      (excitons), both types of excitations have been explored theoretically and
      experimentally. In contrast, studies of charged trions have so far been limited
      to the intralayer type. Here we investigate the complete set of interlayer
      excitations in a MoS2/WS2 heterostructure using a novel ab initio method, which
      allows for a consistent treatment of both excitons and trions at the same
      theoretical footing. Our calculations predict the existence of bound interlayer
      trions below the neutral interlayer excitons. We obtain binding energies of 18/28
      meV for the positive/negative interlayer trions with both electrons/holes located
      on the same layer. In contrast, a negligible binding energy is found for trions
      which have the two equally charged particles on different layers. Our results
      advance the understanding of electronic excitations in doped van der Waals
      heterostructures and their effect on the optical properties.

PMID- 29377702
TI  - Precise Liquid Transport on and through Thin Porous Materials.
AB  - Porous substrates have the ability to transport liquids not only laterally on
      their open surfaces but also transversally through their thickness.
      Directionality of the fluid transport can be achieved through spatial wettability
      patterning of these substrates. Different designs of wettability patterns are
      implemented herein to attain different schemes (modes) of three-dimensional
      transport in a high-density paper towel, which acts as a thin porous matrix
      directing the fluid. All schemes facilitate precise transport of metered liquid
      microvolumes (dispensed as droplets) on the surface and through the substrate.
      One selected mode features lateral fluid transport along the bottom surface of
      the substrate, with the top surface remaining dry, except at the initial droplet
      dispension point. This configuration is investigated in further detail, and an
      analytical model is developed to predict the temporal variation of the
      penetrating drop shape. The analysis and respective measurements agree within the
      experimental error limits, thus confirming the model's ability to account for the
      main transport mechanisms.

PMID- 29377701
TI  - Strongly Cavity-Enhanced Spontaneous Emission from Silicon-Vacancy Centers in
      Diamond.
AB  - Quantum emitters are an integral component for a broad range of quantum
      technologies, including quantum communication, quantum repeaters, and linear
      optical quantum computation. Solid-state color centers are promising candidates
      for scalable quantum optics due to their long coherence time and small
      inhomogeneous broadening. However, once excited, color centers often decay
      through phonon-assisted processes, limiting the efficiency of single-photon
      generation and photon-mediated entanglement generation. Herein, we demonstrate
      strong enhancement of spontaneous emission rate of a single silicon-vacancy
      center in diamond embedded within a monolithic optical cavity, reaching a regime
      in which the excited-state lifetime is dominated by spontaneous emission into the
      cavity mode. We observe 10-fold lifetime reduction and 42-fold enhancement in
      emission intensity when the cavity is tuned into resonance with the optical
      transition of a single silicon-vacancy center, corresponding to 90% of the
      excited-state energy decay occurring through spontaneous emission into the cavity
      mode. We also demonstrate the largest coupling strength (g/2pi = 4.9 +/- 0.3 GHz)
      and cooperativity (C = 1.4) to date for color-center-based cavity quantum
      electrodynamics systems, bringing the system closer to the strong coupling
      regime.

PMID- 29377703
TI  - Effect of Preferential Orientation of Lamellae in the Interfacial Region between
      a Block Copolymer-based Pressure-Sensitive Adhesive and a Solid Substrate on the
      Peel Strength.
AB  - We have investigated the relationship between the peel strength of a block
      copolymer-based pressure-sensitive adhesive comprising of poly(methyl
      methacrylate) (PMMA) and poly(n-butyl acrylate) (PnBA) components from the
      substrate and the microdomain orientations in the interfacial region between the
      adhesive and the substrate. For the PMMA substrate, the PMMA component in the
      adhesive with a strong affinity for the substrate is attached to the surface of
      the substrate during an aging process of the sample at 140  degrees C. Next, the
      PMMA layer adjacent to the substrate surface is overlaid with a PnBA layer, which
      gets covalently connected, resulting in the horizontal alignment of the lamellae
      in the interfacial region. The peel strength of the adhesive substantially
      increases during aging at 140  degrees C, which takes the same time as the
      completion of the horizontally oriented lamellar structure. However, in the case
      of the polystyrene (PS) substrate, both the components in the adhesive repel the
      substrate, leading to the formation of the vertically oriented lamellar
      structure. As a result, the peel strength of the adhesive with respect to its PS
      substrate does not entirely increase on aging. It is suggested that the peel
      strength of the adhesive is highly correlated with the interfacial energy between
      the adhesive and substrate, which can be estimated from the microdomain
      orientation in the interfacial region.

PMID- 29377704
TI  - Calculation of Dipole-Forbidden 5f Absorption Spectra of Uranium(V) Hexa-Halide
      Complexes.
AB  - Restricted-active-space wave function calculations including spin-orbit coupling,
      in combination with Kohn-Sham density functional calculations of vibrational
      modes, were used to determine the vibronic and electronic absorption intensities
      of the near-infrared electric dipole-forbidden 5f-5f transitions of
      representative uranium(V) hexa-halide complex ions. The agreement with
      experimentally assigned vibronic and electronic transitions measured for powder
      or solution samples of salts of the complex ions is reasonable overall and
      excellent for the experimentally best-resolved E5/2u -> E5/2u' bands. The
      intensity of the vibronic transitions may be borrowed from ligand-to-metal charge
      transfer excitations as well as 5f-to-6d metal-centered transitions. Magnetically
      allowed electronic transitions contribute to the two lower-frequency bands of the
      ligand-field spectrum.

PMID- 29377705
TI  - Flow-Driven Assembly of Microcapsules into Three-Dimensional Towers.
AB  - By harnessing biochemical signaling and chemotaxis, unicellular slime molds can
      aggregate on a surface to form a long, vertical stalk. Few synthetic systems can
      self-organize into analogous structures that emerge out of the plane. Through
      computational modeling, we devise a mechanism for assembling tower-like
      structures using microcapsules in solution as building blocks. In the
      simulations, chemicals diffusing from a central patch on a surface produce a
      concentration gradient, which generates a radially directed diffusioosmotic flow
      along the surface toward the center. This toroidal roll of a fluid pulls the
      microcapsules along the surface and lifts them above the patch. As more capsules
      are drawn toward the patch, some units are pushed off the surface but remain
      attached to the central microcapsule cluster. The upward-directed flow then draws
      out the cluster into a tower-like shape. The final three-dimensional (3D)
      structure depends on the flow field, the attractive capsule-capsule and capsule
      surface interaction strengths, and the sedimentation force on the capsules. By
      tuning these factors, we can change the height of the structures that are
      produced. Moreover, by patterning the areas of the wall that are attractive to
      the capsules, we can form multiple vertical strands instead of a single tower.
      Our approach for flow-directed assembly can permit the growth of reconfigurable,
      3D structures from simple subunits.

PMID- 29377706
TI  - Correlation of Surface Adsorption and Oxidation with a Floatability Difference of
      Galena and Pyrite in High-Alkaline Lime Systems.
AB  - When it comes to Pb-Zn ores with high amounts of pyrite, the major problem
      encountered is the low separation efficiency between galena and pyrite. By virtue
      of high dosage of lime and collector sodium diethyl dithiocarbamate (DDTC),
      pyrite and zinc minerals are depressed, allowing the galena to be floated.
      However, there have been significant conflicting reports on the flotation
      behavior of galena at high pH. In this context, correlation of the surface
      adsorption and oxidation with the floatability difference of galena and pyrite in
      high-alkaline lime systems would be a key issue for process optimization. Captive
      bubble contact angle measurements were performed on freshly polished mineral
      surfaces in situ exposed to lime solutions of varying pH as a function of
      immersion time. Furthermore, single mineral microflotation tests were conducted.
      Both tests indicated that the degree of hydrophobicity on the surfaces of galena
      and pyrite increased in the presence of DDTC at natural or mild pulp pH. While in
      a saturated lime solution, at pH 12.5, DDTC only worked for galena, but not for
      pyrite. Surface chemistry analysis by time-of-flight secondary ion mass
      spectrometry (Tof-SIMS) confirmed the preference of DDTC on the galena surface at
      pH 12.5, which contributed to a merit recovery. Further important evidence
      through measurements of Tof-SIMS, ion chromatography, and high-performance liquid
      chromatography indicated that in high-alkaline lime systems, the merit
      floatability of galena could exclude the insignificant contribution of elemental
      sulfur (S8) and was dominantly attributed by the strong adsorption of DDTC. In
      contrast, the poor flotation response of pyrite at high pH was due to the
      prevailing adsorption of CaOH+ species. This study provides an important surface
      chemistry evidence for a better understanding of the mechanism on the better
      selectivity in the galena-pyrite separation adopting high-alkaline lime systems.

PMID- 29377707
TI  - Surface-Enhanced Raman Spectroscopy of Carbon Nanomembranes from Aromatic Self
      Assembled Monolayers.
AB  - Surface-enhanced Raman scattering spectroscopy (SERS) was employed to investigate
      the formation of self-assembled monolayers (SAMs) of biphenylthiol, 4'-nitro-1,1'
      biphenyl-4-thiol, and p-terphenylthiol on Au surfaces and their structural
      transformations into carbon nanomembranes (CNMs) induced by electron irradiation.
      The high sensitivity of SERS allows us to identify two types of Raman scattering
      in electron-irradiated SAMs: (1) Raman-active sites exhibit similar bands as
      those of pristine SAMs in the fingerprint spectral region, but with indications
      of an amorphization process and (2) Raman-inactive sites show almost no Raman
      scattering signals, except a very weak and broad D band, indicating a lack of
      structural order but for the presence of graphitic domains. Statistical analysis
      showed that the ratio of the number of Raman-active sites to the total number of
      measurement sites decreases exponentially with increasing the electron
      irradiation dose. The maximum degree of cross-linking ranged from 97 to 99% for
      the three SAMs. Proof-of-concept experiments were conducted to demonstrate
      potential applications of Raman-inactive CNMs as a supporting membrane for Raman
      analysis.

PMID- 29377708
TI  - A Critical Review of Analytical Methods for Determination of Ceftriaxone Sodium.
AB  - Ceftriaxone sodium is a third-generation semi-synthetic antibiotic belonging to
      the class of cephalosporins. Is administered only by parenteral route and has the
      ability to cross the blood-brain barrier. It has bactericidal action; its main
      activity is related to the Gram-negative bacteria, being also able to act against
      Gram-negative bacilli resistant to the first- and second-generation
      cephalosporins. The present study presents a survey of the characteristics,
      properties and analytical methods used for the determination of ceftriaxone
      sodium, for the gathering of data searches were carried out in scientific
      articles in the world literature, as well as in the official compendia. It is
      necessary to create awareness about the importance of developing effective and
      reliable analytical methods for quality control and consequently for conducting
      pharmacokinetic, bioavailability, bioequivalence studies as well as for the
      therapeutic monitoring of this drug. Most of the methods found use high
      performance liquid chromatography, but also methods that use absorption
      spectroscopy ultraviolet, infrared spectroscopy, spectrofluorimetry and
      microbiological methods have been presented. A discussion was presented
      highlighting the need to develop new ecological methods using less toxic
      solvents, rapid analysis and miniaturization of the samples.

PMID- 29377710
TI  - Incidence, Severity, and Time Loss Associated With Collegiate Football Fractures,
      2004-2005 to 2013-2014.
AB  - BACKGROUND: The inherent risk of any time loss from physical injury in football
      has been extensively discussed, with many such injuries having a profound effect
      on the lives of National Collegiate Athletic Association (NCAA) football players.
      However, the incidence of fractures in collegiate football has not been well
      established. PURPOSE: To examine the epidemiology of fractures in NCAA football.
      STUDY DESIGN: Descriptive epidemiology study. METHODS: Fracture data reported in
      college football during the 2004-2005 to 2013-2014 academic years were analyzed
      from the NCAA Injury Surveillance Program (NCAA-ISP). Fracture rates per 1000
      athlete-exposures, surgery and time loss distributions, injury rate ratios,
      injury proportion ratios (IPRs), and 95% CIs were reported. RESULTS: Overall, 986
      fractures were reported. The rate of competition fractures was larger than the
      rate of practice fractures (1.80 vs 0.17 per 1000 athlete-exposures; injury rate
      ratio = 10.56; 95% CI, 9.32-11.96). Fractures of the hand/fingers represented
      34.6% of all injuries, while fibula fractures (17.2%) were also common. A
      majority (62.5%) of all fractures resulted in time loss >21 days. Altogether,
      34.4% of all fractures required surgery, and 6.3% were recurrent. The proportion
      of fractures resulting in time loss >21 days was higher for fractures requiring
      surgery than fractures not requiring surgery (85.0% vs 50.7%; IPR = 1.68; 95% CI,
      1.53-1.83). The proportion of recurrent and nonrecurrent fractures requiring
      surgery did not differ (35.5% vs 34.3%; IPR = 1.03; 95% CI, 0.73-1.46); however,
      recurrent fractures were more likely to require surgery than nonrecurrent
      fractures when restricted to the hand/fingers (66.7% vs 27.2%; IPR = 2.45; 95%
      CI, 1.36-4.44). CONCLUSION: Fractures in collegiate football were sustained at a
      higher rate in competition than practice and frequently required extended time
      lost from participation, particularly among those requiring surgery. Prevention
      strategies are warranted to reduce incidence and severity of fractures.

PMID- 29377711
TI  - The Period Prevalence of Mind and Body Practice Use by Adult Emergency Department
      Patients.
AB  - OBJECTIVES: Mind and Body Practice (MBP) use (e.g., chiropractic, acupuncture,
      meditation) among Emergency Department (ED) patients is largely unknown. We aimed
      to determine the period prevalence, nature of MBP use, and perceptions of MBP
      among adult ED patients. DESIGN AND SETTING: We undertook a cross-sectional
      survey of a convenience sample of patients presenting to three EDs between
      February and June 2016. SUBJECTS: Patients were eligible for inclusion if they
      were aged 18 years or more and had presented for medical treatment. INTERVENTION:
      An anonymous, self-administered questionnaire, based upon a validated pediatric
      questionnaire, was completed by the patient, with assistance if required. OUTCOME
      MEASURES: The primary outcome was the nature and 12 month period prevalence of
      MBP use. Secondary outcomes were variables associated with use and patient
      perceptions of MBP. RESULTS: 674 patients were enrolled. In the previous 12
      months, 500 (74.2%) patients had used at least one MBP. MBP users and nonusers
      did not differ in gender, ancestry, or chronic illness status (p > 0.05).
      However, users were significantly younger and more likely to have private health
      insurance (p < 0.001). A total of 2094 courses of 68 different MBP had been used
      including massage (75.0% of users), meditation (35.2%), chiropractic (32.6%),
      acupuncture (32.0%), and yoga (30.6%). Users were significantly more likely (p <
      0.01) to believe that MBP prevented illness, treated illness, were more effective
      than prescription medicines, assisted prescription medications, and were safe and
      provided a more holistic approach. Forty-one (6.1%) patients used MBP for their
      ED presenting complaint. However, only 14 (34.1%) advised their ED physician of
      this. CONCLUSION: The period prevalence of MBP use among ED patients is high.
      Knowledge of the MBP used for a patient's presenting complaint may better inform
      the ED physician when making management decisions.

PMID- 29377709
TI  - Physicochemical Investigations of Homeopathic Preparations: A Systematic Review
      and Bibliometric Analysis-Part 1.
AB  - OBJECTIVES: The last systematic review of physicochemical research performed on
      homeopathic preparations was published in 2003. The aim of the study is to update
      and expand the current state of knowledge in the area of physicochemical
      properties of homeopathic preparations. In part 1 of the study, we aim to present
      an overview of the literature with respect to publication quality and methods
      used. In part 2, we aim to identify the most interesting experimental techniques.
      With this, we aim to be in a position to generate meaningful hypotheses regarding
      a possible mode of action of homeopathic preparations. METHODS: A two-step
      procedure was adopted: (1) an extensive literature search, followed by a
      bibliometric and quality analysis on the level of publications and (2) a thorough
      qualitative analysis of the individual physicochemical investigations found. In
      this publication, we report on step (1). We searched major scientific databases
      to find publications reporting physicochemical investigations of homeopathy from
      its origin to the end of 2015. Publications were assessed using a scoring scheme,
      the Manuscript Information Score (MIS). Information regarding country of origin
      of the research and experimental techniques used was extracted. RESULTS: We
      identified 183 publications (compared to 44 in the last review), 122 of which had
      an MIS >=5. The rate of publication in the field was ~2 per year from the 1970s
      until 2000. Afterward, it increased to over 5.5 publications per year. The
      quality of publications was seen to increase sharply from 2000 onward, whereas
      before 2000, only 12 (13%) publications were rated as "high quality" (MIS >=7.5);
      44 (48%) publications were rated as "high quality" from 2000 onward. Countries
      with most publications were Germany (n = 42, 23%), France (n = 29, 16%), India (n
      = 27, 15%), and Italy (n = 26, 14%). Techniques most frequently used were
      electrical impedance (26%), analytical methods (20%), spectroscopy (20%), and
      nuclear magnetic resonance (19%). CONCLUSIONS: Physicochemical research into
      homeopathic preparations is increasing both in terms of quantity and quality of
      the publications.

PMID- 29377712
TI  - Standard PREanalytical Code version 3.0.

PMID- 29377713
TI  - Contributions to Estimation of Polychoric Correlations.
AB  - This research concerns the estimation of polychoric correlations in the context
      of fitting structural equation models to observed ordinal variables by multistage
      estimation. The first main contribution of this research is to propose and
      evaluate a Monte Carlo estimator for the asymptotic covariance matrix (ACM) of
      the polychoric correlation estimates. In multistage estimation, the ACM plays a
      prominent role, as overall test statistics, derived fit indices, and parameter
      standard errors all depend on this quantity. The ACM, however, must itself be
      estimated. Established approaches to estimating the ACM use a sample-based
      version, which can yield poor estimates with small samples. A simulation study
      demonstrates that the proposed Monte Carlo estimator can be more efficient than
      its sample-based counterpart. This leads to better calibration for established
      test statistics, in particular with small samples. The second main contribution
      of this research is a further exploration of the consequences of violating the
      normality assumption for the underlying response variables. We show the
      consequences depend on the type of nonnormality, and the number and location of
      thresholds. The simulation study also demonstrates that overall test statistics
      have little power to detect the studied forms of nonnormality, regardless of the
      ACM estimator.

PMID- 29377714
TI  - Identification of Distinct Latent Classes Related to Sleep, PTSD, Depression, and
      Anxiety in Individuals Diagnosed With Severe Alcohol Use Disorder.
AB  - OBJECTIVE/BACKGROUND: Alcohol use disorders (AUDs) are often accompanied by
      comorbid physiologic and psychosocial conditions, including sleep disturbances.
      Sleep disturbances in these individuals may be associated with increased risk of
      relapse to drinking following detoxification and rehabilitation. PARTICIPANTS:
      The sample of inpatient treatment-seeking individuals with AUDs (N = 164) was
      70.1% male and 47.6% African American with a mean age of 45.6 years (+/-9.5
      years). METHODS: Latent class analysis (LCA) was used to identify unmeasured
      class membership based on seven indicators: maximum Clinical Institute Withdrawal
      Assessment (CIWA) scores; sleep efficiency (actigraphy); sleep disturbances
      (Pittsburgh Sleep Quality Index-PSQI); anxiety or depression (Comprehensive
      Psychopathological Rating Scale [CPRS]); and current and lifetime posttraumatic
      stress disorder (PTSD). RESULTS: The average number of drinking days in the 90
      days preceding admission was 72.0 (+/-22.0 days), with an average of 13.16 drinks
      per day (+/-5.70 drinks). Nearly one quarter (24.4%) of respondents reported
      lifetime PTSD. Three latent classes were identified: Sleep Disturbance (SD);
      Sleep Disturbance, Anxiety and Depression (SD/AD); and Sleep Disturbance, Anxiety
      and Depression, and PTSD (SD/AD/PTSD). Members of the SD/AD/PTSD group were more
      likely to be female and had the highest withdrawal and sleep disturbance scores
      of all three groups. CONCLUSION: Findings support the use of LCA to identify
      subgroups of individuals with AUDs and accompanying sleep disturbances. Class
      identification may provide clinicians with insight into the integrative tailoring
      of interventions that meet the varied needs of individuals with AUDs,
      accompanying comorbidities, and sleep disturbances.

PMID- 29377715
TI  - Fitness Level Modulates Intraocular Pressure Responses to Strength Exercises.
AB  - : Purpose/Aim: The execution of strength exercises has demonstrated to increase
      the intraocular pressure (IOP) levels, and it may have a negative impact on the
      ocular health. We aimed to explore the influence of fitness level on the acute
      IOP response to strength exercises performed under different loading conditions,
      as well as to test whether the IOP responses differ between the bench press and
      jump squat when performed against the same relative loads. MATERIALS AND METHODS:
      Forty military personnel males were divided in two subgroups (20 high-fit and 20
      low-fit) based on their relative to body mass one-repetition maximum (1-RM).
      Participants performed an incremental loading test in the bench press and jump
      squat exercises, and IOP was assessed before and after each repetition by rebound
      tonometry. RESULTS: IOP increased immediately after executing both exercises (p <
      0.01 in both cases), being the magnitude of the IOP increment positively and
      linearly associated with the increment of the load in both groups (i.e., high-fit
      and low-fit) and in both exercises (R2 range: 0.81-1.00). Higher fitness level
      attenuated the IOP rise produced by both exercises (p < 0.01 in both cases). The
      bench press induced higher IOP increments than the jump squat for both groups at
      relative loads of ~50%1-RM and ~60%1-RM (p < 0.01 in all cases). CONCLUSIONS:
      These data indicate that IOP increases as a consequence of performing strength
      exercises, being the increment accentuated with the increase of the load and in
      the bench press compared to the jump squat exercise. Of special importance would
      be that the IOP responses were significantly reduced in high-fit individuals.
      These findings should be addressed in glaucoma patients.

PMID- 29377717
TI  - Impact of Pathologist Involvement in Sarcoma and Rare Tumor Patient Support
      Groups on Facebook: A Survey of 542 Patients and Family Members.
AB  - CONTEXT: - Patients with rare tumors have difficulty finding reliable information
      about their disease. Facebook patient support groups allow patients to educate
      one another. OBJECTIVE: - To investigate how these patients perceive the value of
      pathologists, both in Facebook groups and real-world patient care. DESIGN: -
      Survey links were posted in 12 Facebook patient groups: 6 with an active
      pathologist member (angiosarcoma, epithelioid hemangioendothelioma, epithelioid
      sarcoma, dermatofibrosarcoma protuberans [*2], and desmoid fibromatosis), and 6
      without "active" pathologist involvement (aggressive angiomyxoma, chondrosarcoma,
      Ewing sarcoma, leiomyosarcoma, liposarcoma, and osteosarcoma). RESULTS: - A total
      of 542 people responded (403 were patients): 264 from groups with a pathologist,
      and 278 from groups without active pathologist involvement. Of groups with an
      active pathologist, respondents agreed the pathologist's posts helped them better
      understand their disease (107 of 119; 90%) and relieved some of their disease
      related anxiety (92 of 119; 77%). And for these groups 98% (117 of 119) of
      respondents agreed that having a pathologist in their group was a good thing; 83%
      (192 of 232) wanted more pathologists involved. More respondents from groups with
      an active pathologist (219 of 236; 93%) than without one (215 of 252; 85%)
      agreed: "pathologists are an important part of the patient care team for patients
      with cancer and other rare tumors" ( P = .008). CONCLUSIONS: - This study is the
      first to evaluate the impact of pathologist interaction with Facebook patient
      support groups and to assess perceptions about the specialty of pathology from a
      large group of patients with rare tumors. Pathologist involvement in Facebook
      patient groups appears to positively influence patient perception of the
      importance of pathologists. We hope these data will encourage more pathologists
      to participate in Facebook patient support groups.

PMID- 29377716
TI  - The UK Centre for Astrobiology: A Virtual Astrobiology Centre. Accomplishments
      and Lessons Learned, 2011-2016.
AB  - The UK Centre for Astrobiology (UKCA) was set up in 2011 as a virtual center to
      contribute to astrobiology research, education, and outreach. After 5 years, we
      describe this center and its work in each of these areas. Its research has
      focused on studying life in extreme environments, the limits of life on Earth,
      and implications for habitability elsewhere. Among its research infrastructure
      projects, UKCA has assembled an underground astrobiology laboratory that has
      hosted a deep subsurface planetary analog program, and it has developed new flow
      through systems to study extraterrestrial aqueous environments. UKCA has used
      this research backdrop to develop education programs in astrobiology, including a
      massive open online course in astrobiology that has attracted over 120,000
      students, a teacher training program, and an initiative to take astrobiology into
      prisons. In this paper, we review these activities and others with a particular
      focus on providing lessons to others who may consider setting up an astrobiology
      center, institute, or science facility. We discuss experience in integrating
      astrobiology research into teaching and education activities. Key Words:
      Astrobiology-Centre-Education-Subsurface-Analog research. Astrobiology 18, 224
      243.

PMID- 29377718
TI  - Potential interactions among phenolic compounds and probiotics for mutual
      boosting of their health-promoting properties and food functionalities - A
      review.
AB  - Several foods are rich sources of phenolic compounds (PC) and their beneficial
      effects on human health may be increased through the action of probiotics.
      Additionally, probiotics may use PC as substrates, increasing their survival and
      functionality. This review presents available studies on the effects of PC on
      probiotics, including their physiological functionalities, interactions and
      capability of surviving during exposure to gastrointestinal conditions and when
      incorporated into food matrices. Studies have shown that PC can improve the
      adhesion capacity and survival of probiotics during exposure to conditions that
      mimic the gastrointestinal tract. There is strong evidence that PC can modulate
      the composition of the gut microbiota in hosts, improving a variety of
      biochemical markers and risk factors for chronic diseases. Available literature
      also indicates that metabolites of PC formed by intestinal microorganisms,
      including probiotics, exert a variety of benefits on host health. These
      metabolites are typically more active than parental dietary PC. The presence of
      PC commonly enhances probiotic survival in different foods. Finally, further
      clinical studies need to be developed to confirm in vitro and experimental
      findings concerning the beneficial interactions among different PC and
      probiotics.

PMID- 29377719
TI  - Prevalence and Antibiotic Resistance Profiles of Campylobacter jejuni Isolated
      from Poultry Meat and Related Samples at Retail Shops in Northern India.
AB  - Campylobacteriosis is the common gastrointestinal disease worldwide. However, in
      many parts of the world, including India, the impact of campylobacteriosis is
      less commonly investigated. This study aimed to determine the prevalence and
      antibiotic susceptibility profiles of Campylobacter jejuni in raw poultry meat
      and poultry-related samples at retail shops in a region of Northern India. A
      total of 400 samples of chicken meat (150), chicken intestine (150), feathers
      (50), and chopping boards and knives (50) samples were screened for the presence
      of C. jejuni by selective enrichment culture followed by selective plating on
      mCCDA and also by polymerase chain reaction (PCR) after selective enrichment. The
      highest prevalence of Campylobacter contamination (38.6%) was observed in chicken
      meat followed by chicken intestine (24.0%). C. jejuni was detected in 14.0% of
      chopping boards, knives, and feather samples by culturing method. The hipO gene
      based PCR detection yielded 36.0% C. jejuni from chicken meat samples; in other
      samples, however, the prevalence of C. jejuni was observed similar to that of
      cultural method. The antibiotic susceptibility profiles confirmed drug resistance
      among 97% of C. jejuni isolates, with 84.1% of C. jejuni isolates resistant to co
      trimoxazole followed by cephalothin (81.1%) and tetracycline (59.4%). Low
      incidence of resistance (6.9-8.9%) was observed against nalidixic acid,
      ciprofloxacin, erythromycin, gentamicin, and azithromycin. Resistance to multiple
      drugs (>=4) was recorded in 31.6% of the strains. The findings of this study
      demonstrated high prevalence of drug-resistant C. jejuni in raw chicken meat and
      intestinal isolates. The high occurrence of C. jejuni in chicken meat might be
      due to cross contamination as a result of slaughtering and poor hygienic
      conditions. Implementation of monitoring/surveillance programs to monitor the
      prevalence of multidrug-resistant Campylobacter spp. in food production animals,
      particularly, poultry in semiurban regions, as well as main cities in India, is
      highly required for better public health protection.

PMID- 29377720
TI  - Campylobacter and Ethnicity-A Case-Case Analysis to Determine Differences in
      Disease Presentation and Risk Factors.
AB  - BACKGROUND: Rates of Campylobacter infection in Arizona have historically been
      higher than the national average, with the highest rates in Hispanic populations.
      The purpose of this retrospective case-case analysis was to determine how risk
      factors and disease presentation differ by ethnicity (Hispanic vs. Non-Hispanic)
      in cases of campylobacteriosis from 2012 to 2015 in Maricopa County, Arizona.
      METHODS: Basic demographics and seasonality, including standardized morbidity
      ratios (SMRs), were analyzed to determine differences by ethnicity. To determine
      differences in risk factors, adjusted univariate and multivariable logistic
      regression was conducted. RESULTS: There were significant differences by
      ethnicity by age (1-14 years and >60 years), location of residence (urban vs.
      suburban), and testing methodology. Most months in the seasonality analysis
      showed higher than expected values of Hispanic cases based on population
      distributions (SMR Range: 0.91-1.78, annual mean: 1.23). Differences in disease
      presentation showed that Hispanics (adjusted for age and location of residence)
      were more likely to experience vomiting (OR = 1.41) and fever (OR = 1.08), as
      well as seek care through an urgent care or emergency department (OR = 1.50),
      than non-Hispanic cases. Hispanics had a higher odds of reporting consumption of
      tomatoes (OR = 1.45), salsa (OR = 2.35), cilantro (OR = 2.21), queso fresco (OR =
      8.53), and sprouts (OR = 1.94) than non-Hispanic cases. Multivariable analyses
      found queso fresco (aOR = 6.58), cilantro (aOR = 3.93), and animal products (aOR
      = 0.38) all to be significant by ethnicity. CONCLUSIONS: Hispanics had a higher
      likelihood of consuming high risk foods, while non-Hispanics were more likely to
      have environmental exposures linked to Campylobacter infection. Focused
      questionnaires can reveal differences and contribute to improving public health
      action/education for specific populations.

PMID- 29377721
TI  - Glenoid Bone Loss in Posterior Shoulder Instability: Prevalence and Outcomes in
      Arthroscopic Treatment.
AB  - BACKGROUND: Glenoid bone loss is a well-accepted risk factor for failure after
      arthroscopic stabilization of anterior glenohumeral instability. Glenoid bone
      loss in posterior instability has been noted relative to its existence in
      posterior instability surgery. Its effect on outcomes after arthroscopic
      stabilization has not been specifically evaluated and reported. PURPOSE: The
      purpose was to evaluate the presence of posterior glenoid bone loss in a series
      of patients who had undergone arthroscopic isolated stabilization of the
      posterior labrum. Bone loss was then correlated to return-to-duty rates,
      complications, and validated patient-reported outcomes. STUDY DESIGN: Case
      control study; Level of evidence, 3. METHODS: A retrospective review was
      conducted at a single military treatment facility over a 4-year period (2010
      2013). Patients with primary posterior instability who underwent arthroscopic
      isolated posterior labral repair were included. Preoperative magnetic resonance
      imaging was used to calculate posterior glenoid bone loss using a standardized
      "perfect circle" technique. Demographics, return to duty, complications, and
      reoperations, as well as outcomes scores including the Single Assessment Numeric
      Evaluation and the Western Ontario Shoulder Instability Index (WOSI) scores, were
      obtained. Outcomes were analyzed across all patients based on percentage of
      posterior glenoid bone loss. Bone loss was then categorized as below or above the
      subcritical threshold of 13.5% to determine if bone loss effected outcomes
      similar to what has been shown in anterior instability. RESULTS: There were 43
      consecutive patients with primary, isolated posterior instability, and 32 (74.4%)
      completed WOSI scoring. Mean follow-up was 53.7 months (range, 25-82 months) The
      mean posterior glenoid bone loss was 7.3% (0%-21.5%). Ten of 32 patients (31%)
      had no appreciable bone loss. Bone loss exceeded 13.5% in 7 of 32 patients (22%),
      and 2 patients (6%) exceeded 20% bone loss. Return to full duty or activity was
      nearly 90% overall. However, those with >13.5%, subcritical glenoid bone loss,
      were statistically less likely to return to full duty (relative risk = 1.8), but
      outcomes scores, complications, and revision rates were otherwise not different
      in those with no or minimal bone loss versus those with more significant amounts.
      CONCLUSION: Posterior glenoid bone loss has not previously been evaluated
      independently relative to patients with shoulder instability repairs. Sixty-nine
      percent of our patients had measurable bone loss, and 22% had greater than 13.5%,
      or above subcritical bone loss. While these patients were statistically less
      likely to return to full duty, the reoperation rate, complications, and patient
      reported outcomes between groups were not different.

PMID- 29377722
TI  - Antibacterial Activities of Endophytic Bacteria Isolated from Taxus brevifolia
      Against Foodborne Pathogenic Bacteria.
AB  - Endophytes are a potential source of novel bioactive compounds with medicinal
      properties. In this study, 41 endophytic bacteria (EB) were isolated from tissues
      of a medicinally important plant Taxus brevifolia (Pacific yew). The objective
      was to screen all the EB isolates for their antibacterial effects against five
      foodborne pathogenic bacteria: Bacillus cereus ATCC10876, Staphylococcus aureus
      ATCC12600, Listeria monocytogenes ATCC19115, Escherichia coli ATCC43890, and
      Salmonella Typhimurium ATCC19585. Among the EB isolates, T. brevifolia seed (TbS)
      8, T. brevifolia fleshy part of fruit (TbFl)-10, T. brevifolia leaf (TbL)-22, TbS
      29, and TbL-34 exerted significant antibacterial activity against the tested
      foodborne pathogens. Especially TbFl-10 showed the highest antibacterial activity
      against all the tested bacteria and was identified as Paenibacillus kribbensis
      (Pk). Furthermore, an ethyl acetate extract of Pk-TbFl-10 possessed antibacterial
      activities against the tested five foodborne pathogenic bacteria, with zones of
      inhibition from 15.71 +/- 2.85 to 13.01 +/- 2.12 mm. Scanning electron microscopy
      analysis revealed ruptured, lysed, shrunk, and swollen cells of all the tested
      foodborne pathogens treated with the ethyl acetate extract of Pk-TbFl-10,
      suggesting that a metabolite(s) of Pk-TbFl-10 penetrates the cell membrane and
      causes cell lysis leading to cell death. Our results indicate that Pk-TbFl-10
      isolated from T. brevifolia can serve as a novel source of natural antibacterial
      agents against foodborne pathogenic bacteria, with potential applications in the
      pharmaceutical industry.

PMID- 29377724
TI  - Only Bad for Believers? Religion, Pornography Use, and Sexual Satisfaction Among
      American Men.
AB  - Research has often demonstrated a negative association between pornography use
      and various intrapersonal and relationship outcomes, particularly for men.
      Several recent studies, however, have suggested that the negative association
      between pornography use and these indicators is stronger among more religious
      Americans, suggesting that moral incongruence (engaging in an activity that
      violates one's sacred values) and the attendant shame or cognitive dissonance,
      rather than pornography use per se, may be the primary factor at work. The
      current study tested and extended this theory by examining how religion
      potentially moderates the link between pornography use and sexual satisfaction in
      a national random sample of American adults (N = 1,501). Analyses demonstrated
      that while pornography use was negatively associated with sexual satisfaction for
      American men (not women), among men who rarely attended religious services or
      held a low opinion of the Bible this negative association essentially
      disappeared. Conversely, the negative association between frequency of
      pornography consumption and sexual satisfaction was more pronounced for men with
      stronger ties to conventional religion. These findings suggest that the
      connection between pornography use and sexual satisfaction, especially for men,
      depends largely on what viewing pornography means to consumers and their moral
      community and less so on the practice itself.

PMID- 29377723
TI  - Facial Expressiveness in Infants With and Without Craniofacial Microsomia:
      Preliminary Findings.
AB  - OBJECTIVE: To compare facial expressiveness (FE) of infants with and without
      craniofacial macrosomia (cases and controls, respectively) and to compare
      phenotypic variation among cases in relation to FE. DESIGN: Positive and negative
      affect was elicited in response to standardized emotion inductions, video
      recorded, and manually coded from video using the Facial Action Coding System for
      Infants and Young Children. SETTING: Five craniofacial centers: Children's
      Hospital of Los Angeles, Children's Hospital of Philadelphia, Seattle Children's
      Hospital, University of Illinois-Chicago, and University of North Carolina-Chapel
      Hill. PARTICIPANTS: Eighty ethnically diverse 12- to 14-month-old infants. MAIN
      OUTCOME MEASURES: FE was measured on a frame-by-frame basis as the sum of 9
      observed facial action units (AUs) representative of positive and negative
      affect. RESULTS: FE differed between conditions intended to elicit positive and
      negative affect (95% confidence interval = 0.09-0.66, P = .01). FE failed to
      differ between cases and controls (ES = -0.16 to -0.02, P = .47 to .92). Among
      cases, those with and without mandibular hypoplasia showed similar levels of FE
      (ES = -0.38 to 0.54, P = .10 to .66). CONCLUSIONS: FE varied between positive and
      negative affect, and cases and controls responded similarly. Null findings for
      case/control differences may be attributable to a lower than anticipated
      prevalence of nerve palsy among cases, the selection of AUs, or the use of manual
      coding. In future research, we will reexamine group differences using an
      automated, computer vision approach that can cover a broader range of facial
      movements and their dynamics.

PMID- 29377725
TI  - Preadolescents' Daily Peer Victimization and Perceived Social Competence:
      Moderating Effects of Classroom Aggression.
AB  - Few studies have assessed children's daily peer experiences, and even fewer have
      considered their daily self-perceptions. This daily diary study examined
      relations between preadolescents' daily reports of peer victimization and
      perceived social competence, along with moderating effects of classroom
      aggression. A racially diverse sample of 182 children in 5th grade (105 boys; M
      age = 10.64 years; 35% White, 31% Black, 17% Hispanic, 17% other or not reported)
      completed daily measures of peer victimization and perceived social competence,
      with most children completing measures on 8 school days. Teachers completed
      measures of aggression for each participating pupil. Four types of peer
      victimization (verbal victimization, social manipulation, social rebuff, and
      property attacks) predicted decreased daily perceived social competence. Daily
      social rebuff predicted decreased daily perceived social competence beyond the
      effects of the other types of victimization. Classroom aggression moderated the
      relation of verbal victimization with perceived social competence, such that this
      relation was significant in classrooms with lower aggression and nonsignificant
      in classrooms with higher aggression. Results indicate that preadolescents' daily
      self-perceptions fluctuate with daily victimization by peers, particularly with
      social rebuff. Findings also suggest that the impact of verbal victimization on
      children's self-views could be exacerbated in classrooms that better manage peer
      to-peer aggression. Accordingly, targeted interventions appear critical for
      children who continue to experience peer victimization in schools with highly
      effective aggression prevention programs.

PMID- 29377726
TI  - Cognitive Bridging: Using Strategic Communication To Connect Abstract Goals With
      The Means To Achieve Them.
AB  - Three studies test several mechanisms of cognitive bridging, or how a strategic
      communication message functions to connect the abstract goal of an individual
      with the specific means to achieve the goal. Across all of the experiments (n =
      276, n = 209, n = 145), it was demonstrated that participants who received an
      induced bridging mechanism were more likely to produce cognitive bridging outputs
      and report more abstract responses than participants who did not receive a
      bridging technique. We do not find the same pattern of results among participants
      who received an integrated bridging technique. Taken together, these studies
      provide evidence that how abstractly or concretely an individual is thinking can
      be influenced by abstraction cues planted within a strategic message, providing
      promise for messaging efforts at the moment of decision. In other words, the
      level of abstract thinking an individual is carrying into an exposure situation
      is possible to change using cues within the message itself. This is the first
      article to juxtapose the induced and integrated mechanisms of cognitive bridging.

PMID- 29377727
TI  - Developmental progression and side specialization in upper-limb movements from 4
      to 8 years in children born preterm and fullterm.
AB  - This study investigated developmental changes and differences in upper-limb
      movement organization from 4 to 8 years of age in children born preterm (PT) and
      fullterm (FT). Kinematic recordings of precision-demanding unimanual movements
      and lateral assessments were carried out in 37 children (18 PT). All children,
      particularly children born PT, displayed considerable gain in movement
      kinematics. Contrary to controls, children born PT displayed persistently less
      evident side preference. Gestational age (GA) contributed significantly to
      kinematic differences shown, with larger upper-limb deviances in the lowest GAs,
      in agreement with cross-sectional findings of altered hemispheric connections and
      delayed side-specialization among children born very PT.

PMID- 29377728
TI  - Milk Volume at 2 Weeks Predicts Mother's Own Milk Feeding at Neonatal Intensive
      Care Unit Discharge for Very Low Birthweight Infants.
AB  - OBJECTIVE: This study sought to determine the maternal prepregnancy, pregnancy,
      and delivery risk factors that predicted coming to volume (CTV; achieving pumped
      mother's own milk [MOM] volume >=500 mLs/day) and the continuation of MOM
      provision through to discharge from the neonatal intensive care unit (NICU) in
      mothers and their very low birthweight (VLBW; <1,500 g at birth) infants. STUDY
      DESIGN: Secondary analysis of prospectively collected data from 402 mothers of
      VLBW infants admitted to an urban NICU, including detailed MOM pumping records
      for a subset (51%) of the cohort. Analyses included inverse probability
      weighting, multivariate regression, and chi-square statistics. RESULTS: In this
      high-risk cohort (51.2% black, 27.1% Hispanic, 21.6% white/Asian; 72.6% low
      income; 61.4% overweight/obese prepregnancy), CTV by day 14 was the strongest
      predictor of MOM feeding at NICU discharge (odds ratio [OR] 9.70 confidence
      interval [95% CI] 3.86-24.38, p < 0.01.). Only 39.5% of mothers achieved CTV by
      postpartum day 14, an outcome that was predicted by gestational age at delivery
      (OR 1.41, 95% CI 1.15-1.73, p < 0.01), being married (OR 3.66, 95% CI 1.08-12.39,
      p = 0.04), black race (OR 7.70, 95% CI 2.05-28.97, p < 0.01), cesarean delivery
      (OR 0.22, 95% CI 0.08-0.63, p = 0.01), and chorioamionitis (OR 0.14, 95% CI 0.02
      0.82, p = 0.03). CONCLUSION: Continued provision of MOM at NICU discharge can be
      predicted in the first 14 postpartum days on the basis of achievement of CTV. We
      posit that CTV can serve as a quality indicator for improving MOM feedings in the
      NICU and that lactation support resources should target this early critical
      postbirth period.

PMID- 29377729
TI  - Computed Tomography Measurements as a Standard of Exophthalmos? Two-Dimensional
      Versus Three-Dimensional Techniques.
AB  - PURPOSE: To compare measurements of exophthalmos using two-dimensional (2D) and
      three-dimensional (3D) computed tomography (CT) methods. METHODS: The CT data of
      50 patients with thyroid eye disease were collected. The exophthalmos
      measurements were performed using both 2D and 3D methods. The protrusion of the
      globe center, the deviation angle of the ocular axis, and the distance between
      the globe center and the corneal apex were also recorded. The agreements between
      Hertel exophthalmometry and different CT measurements were analyzed, and the
      geometrical relationship between the protrusion of the corneal apex and globe
      center were analyzed. RESULTS: The measurement agreement from consecutive CT
      scans was significantly better using the 3D method than the 2D method (p < 0.05).
      The difference in exophthalmos measurements between the 2D and 3D methods was 0.9
      +/- 1.2 mm (p < 0.05), and the 3D exophthalmos measurement was more consistent
      with Hertel exophthalmometry. The exophthalmos of the corneal apex and the globe
      center agreed with the geometrical formula well. The location error between the
      corneal apexes marked on the 2D and 3D images was correlated with the vertical
      deviation angle of the ocular axis (r = 0.516). CONCLUSION: The reliability of CT
      measurements performed using a 3D method was better than those obtained using a
      conventional 2D method. The 3D measurements were also more consistent with the
      exophthalmometry results. The exophthalmos of the globe center might be
      considered an important reference for patients with severe strabismus.

PMID- 29377730
TI  - Birth of a field: Neuroscience of creativity.

PMID- 29377732
TI  - Erratum.

PMID- 29377731
TI  - There's a Lot More to Being a Physician: Insights From an Intensive Clinical
      Shadowing Experience in Internal Medicine.
AB  - : Phenomenon: Although most premedical students shadow physicians prior to
      starting medical school, there is no set of guidelines or expectations to
      facilitate effective experiences for students and physicians, nor is there data
      on the value of shadowing medical trainees as a way to learn about the training
      environment. We sought to understand premedical student perspectives on an
      intensive resident shadowing experience. APPROACH: This was a qualitative study
      using anonymous data from focus groups conducted with premedical student
      participants in a month-long time motion analysis of internal medicine interns at
      two large academic medical centers. The authors convened, professionally
      transcribed verbatim, and analyzed data using step-by-step thematic analysis from
      3 focus groups in 2012. Focus group questions included goals of participants,
      shadowing experiences, patient safety experiences, and thoughts on physician
      training. FINDINGS: Twenty of the 22 students who were involved in the time
      motion study participated in the focus groups (91%). Three major themes were
      generated from the transcripts: qualities of a good physician, the inefficiencies
      of the healthcare system and the hospital, and the realities of graduate medical
      education. Insights: The intensive shadowing experience exposed premedical
      students to the hospital environment and many of the challenges they will face as
      future residents. Observing patient care firsthand, students considered the
      qualities of good intern physicians and appreciated the teamwork and
      collaboration essential to patient care in an academic medical center. Students
      witnessed some of the fundamental challenges of graduate medical training,
      including time pressures, documentation requirements, and the medical hierarchy.
      They also observed the difficulties of providing quality care in the current
      healthcare system, including hospital inefficiencies, interprofessional tensions,
      and financial barriers to care. Intensive shadowing of residents can begin the
      process of socialization to the culture of medicine by giving premedical students
      a realistic perspective of both positive and negative aspects of medical training
      and inpatient care.

PMID- 29377734
TI  - Age Cohort Differences in Sexual Behaviors Among Black Men Who Have Sex With Men
      and Women.
AB  - Little attention has focused on generational or age-related differences in human
      immunodeficiency virus/sexually transmitted infection (HIV/STI) risk behaviors
      among Black men who have sex with men and women (BMSMW). We examined sexual risk
      behaviors between BMSMW ages 40 and under compared to over age 40. Analysis was
      conducted using Centers for Disease Control and Prevention (CDC)-sponsored
      intervention data among BMSMW in Los Angeles, Chicago, and Philadelphia (n =
      546). Pearson's chi-square tests were conducted to evaluate associations between
      age groups and behavioral outcomes. Logistic regression was used to evaluate the
      odds of behavioral outcomes by age group, adjusting for sexual orientation and
      study location, within strata of HIV status. HIV-positive BMSMW over age 40 had
      62% reduced odds of having a nonmain female partner of HIV-negative or unknown
      status compared to those ages 40 and under (adjusted odds ratio [AOR] 0.38, 95%
      confidence interval [CI] = 0.15, 0.95). Among HIV-negative BMSMW, the older
      cohort was associated with greater odds of having condomless insertive anal
      intercourse (IAI) with most recent main male partner (AOR 2.44, 95% CI = 1.12,
      5.32) and having a concurrent partnership while with their recent main female
      partner (AOR = 2.6, 95% CI = 1.10, 4.67). For both groups, odds of engaging in
      certain risk behaviors increased with increasing age. Prevention efforts should
      consider generational differences and age in HIV risks among BMSMW.

PMID- 29377735
TI  - The long-term effects of the Kangaroo Mother Care intervention on cognitive
      functioning: Results from a longitudinal study.
AB  - This study aimed to evaluate the long-term effects of the Kangaroo Mother Care
      (KMC) intervention on the intellectual and attentional functioning of young
      adults born with low birth weight. Three hundred infants were randomly assigned
      at birth in one of two interventions, KMC or traditional care (TC), and completed
      cognitive tests at adulthood (19-21 years after recruitment). The main results
      show that participants with a neurological vulnerability at 6 months had higher
      IQ and sustained attention scores at adulthood if they had received KMC than if
      they had received TC.

PMID- 29377736
TI  - Family Related Factors and Concurrent Heroin Use in Methadone Maintenance
      Treatment in China.
AB  - BACKGROUND: The use of heroin during Methadone Maintenance Treatment (MMT) is a
      challenging problem that contributes to poor treatment outcomes. Families may
      play an important role in addressing concurrent heroin use during MMT, especially
      in collectivist societies such as China. OBJECTIVES: In this study, we explored
      the relationship between family-related factors and concurrent heroin use during
      MMT in China. METHODS: This study was conducted at 68 MMT clinics in five
      provinces of China. There were 2,446 MMT clients in the analysis. Demographic
      information, MMT dosage, family members' heroin use status, family support of
      MMT, family problem, and self-reported heroin use were collected in a cross
      sectional survey. The most recent urinalysis of opiate use was obtained from
      clinical records. RESULTS: Of the 2,446 participants, 533 (21.79%) self-reported
      heroin use in the previous seven days or had a positive urine morphine test
      result in the clinic record. Participants whose family member[s] used heroin were
      1.59 times (95% CI: 1.17, 2.15) more likely to use concurrently during treatment.
      Those with family members who totally support them on the MMT were less likely to
      use (AOR: 0.75, 95% CI: 0.60, 0.94). Having more family problems was positively
      associated with concurrent heroin use (AOR: 2.01, 95% CI: 1.03, 3.93).
      CONCLUSIONS: The results highlight the importance of the family's role in
      concurrent heroin use during MMT programs. The study's findings may have
      implications for family-based interventions that address concurrent heroin use.

PMID- 29377737
TI  - Eyes on New Product Development: Preclinical Research.

PMID- 29377738
TI  - Psychological Factors and Their Association with Ideal Cardiovascular Health
      Among Women and Men.
AB  - BACKGROUND: The cardiovascular effects of stress and other psychological factors
      may be different between women and men. We assessed whether self-perceived
      adverse psychological factors were associated with achievement of ideal
      cardiovascular health (CVH) as measured by the American Heart Association's
      Life's Simple Seven (LS7) and whether this differed by sex. METHODS: This was a
      cross-sectional study of employees from a large healthcare organization. The LS7
      metrics (smoking, physical activity, diet, body mass index, blood pressure,
      cholesterol, and glucose) were each scored as ideal (2), intermediate (1), or
      poor (0). Total scores were categorized as optimal (11-14), average (9-10), and
      inadequate (0-8). Using logistic regression, we tested whether psychological
      factors obtained by questionnaire (self-perceived stress, low life satisfaction,
      hopelessness, sadness, depression, and anxiety) were associated with CVH, after
      adjustment for age, ethnicity, and education. RESULTS: Among 9,056 participants,
      the mean (SD) age was 43 (12) years, 74% were women, 57% Hispanic/Latino, 17%
      white, and 16% black. Stress was associated with reduced odds of having
      optimal/average CVH [OR 0.58 (95% CI 0.50-0.66) and 0.63 (0.50-0.81), for women
      and men, respectively]. Similarly, depression was associated with reduced odds of
      optimal/average CVH [0.58 (0.43-0.78) and 0.44 (0.26-0.76), for women and men,
      respectively]. Low life satisfaction, hopelessness, sadness, and anxiety were
      also associated with statistically significantly lower odds of optimal/average
      CVH in women, but not in men; however, there were no interactions by sex.
      CONCLUSIONS: In an ethnically diverse population, both women and men with several
      adverse self-perceived psychological factors were less likely to have optimal or
      adequate CVH. Future studies are needed to determine whether addressing
      psychological stressors can improve CVH.

PMID- 29377739
TI  - In Vivo and In Vitro Anti-Inflammatory Effects of Aqueous Extract of Anthriscus
      sylvestris Leaves.
AB  - Anthriscus sylvestris (L.) Hoffm. is a common perennial herb that is widely
      distributed in Europe, Korea, and New Zealand. The root of A. sylvestris has been
      used in Korean traditional medicine as an antitussive and cough remedy. However,
      the physiologically active function of A. sylvestris leaves is not yet known. In
      this study, we evaluated the anti-inflammatory effects, as well as the underlying
      molecular mechanisms of an aqueous extract of A. sylvestris leaves (AE-ASL) in
      vitro and in vivo. Our results indicated that pretreatment with AE-ASL
      significantly inhibited the lipopolysaccharide (LPS)-induced secretion of nitric
      oxide (NO) and prostaglandin E2 in RAW264.7 cells, without showing cytotoxicity.
      In addition, the LPS-induced mRNA and protein expression of inducible NO
      synthase, cyclooxygenase-2, and inflammatory mediators such as tumor necrosis
      factor alpha interleukin (IL)-1beta, and IL-6 was attenuated by pretreatment with
      AE-ASL in a dose-dependent manner. Therefore, we investigated the activation of
      nuclear factor (NF)-kappaB, a transcription factor regulating the expression of
      inflammation-related genes. AE-ASL inhibited the nuclear translocation of the NF
      kappaB p65 subunit by suppressing the phosphorylation and degradation of the
      inhibitor of NF-kappaB (IkappaBalpha). Further, AE-ASL inhibited the LPS-induced
      phosphorylation of mitogen-activated protein kinases (MAPKs) in RAW264.7 cells.
      Orally administered AE-ASL (50, 100, and 200 mg/kg of body weight [BW])
      suppressed the development of carrageenan-induced rat paw edema by 15%, 31%, and
      40%, respectively, after 4 h. Altogether, our results suggest that AE-ASL
      possesses anti-inflammatory activity, based on the suppression of NF-kappaB and
      MAPK pathways in vitro and inhibition of the carrageenan-induced paw edema in
      vivo.

PMID- 29377740
TI  - Impact of 10% SF6 Gas Compared to 100% Air Tamponade in Descemet's Membrane
      Endothelial Keratoplasty.
AB  - PURPOSE: To compare the clinical outcomes following Descemet's membrane
      endothelial keratoplasty (DMEK) with 100% air tamponade versus 10% sulfur
      hexafluoride (SF6) tamponade. METHODS: Retrospective analysis of 108 consecutive
      DMEK cases subdivided by anterior chamber tamponade with 54 eyes receiving 10%
      SF6 and 54 eyes receiving 100% air injection. A post-hoc matched analysis
      revealed no statistically significant differences between the groups. The main
      outcome measurements were the complication rate, including intra- and
      postoperative complications and graft detachment rate requiring re-bubbling.
      Clinical outcome included best-corrected visual acuity (BCVA), endothelial cell
      count (ECC), and central corneal thickness (CCT) measured 1, 3, and 6 months
      after DMEK surgery. RESULTS: The graft detachment rate with consecutive re
      bubbling was 18.5% in the air group and 22.2% in the SF6 group (p = 0.2).
      Remaining small peripheral graft detachments with a clear cornea occurred more
      often in the 100% air group (air: 22.2%; 12/54, 6/12 inferior compared to SF6:
      7.4%; 4/54, 2/4 inferior; p = 0.06). The primary graft failure rate was
      comparable between the two groups. No complete graft detachment occurred. Outcome
      results for BCVA, ECC, and CCT at all follow-up time points were comparable
      between the two groups. CONCLUSION: The clinical outcomes (including re-bubbling
      rate, primary graft failure rate, and endothelial cell loss) were comparable with
      100% air versus 10% SF6 tamponade, whereas other studies suggest that a higher
      SF6 concentration (20%) may result in a lower re-bubbling rate.

PMID- 29377733
TI  - Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive
      Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.
AB  - OBJECTIVE: Brain imaging studies of structural abnormalities in OCD have yielded
      inconsistent results, partly because of limited statistical power, clinical
      heterogeneity, and methodological differences. The authors conducted meta- and
      mega-analyses comprising the largest study of cortical morphometry in OCD ever
      undertaken. METHOD: T1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy
      controls from 27 sites worldwide were processed locally using FreeSurfer to
      assess cortical thickness and surface area. Effect sizes for differences between
      patients and controls, and associations with clinical characteristics, were
      calculated using linear regression models controlling for age, sex, site, and
      intracranial volume. RESULTS: In adult OCD patients versus controls, we found a
      significantly lower surface area for the transverse temporal cortex and a thinner
      inferior parietal cortex. Medicated adult OCD patients also showed thinner
      cortices throughout the brain. In pediatric OCD patients compared with controls,
      we found significantly thinner inferior and superior parietal cortices, but none
      of the regions analyzed showed significant differences in surface area. However,
      medicated pediatric OCD patients had lower surface area in frontal regions.
      Cohen's d effect sizes varied from -0.10 to -0.33. CONCLUSIONS: The parietal
      cortex was consistently implicated in both adults and children with OCD. More
      widespread cortical thickness abnormalities were found in medicated adult OCD
      patients, and more pronounced surface area deficits (mainly in frontal regions)
      were found in medicated pediatric OCD patients. These cortical measures represent
      distinct morphological features and may be differentially affected during
      different stages of development and illness, and possibly moderated by disease
      profile and medication.

PMID- 29377741
TI  - The effect of a local promotional campaign on preconceptional lifestyle changes
      and the use of preconception care.
AB  - PURPOSE: The objective of this study was to investigate the effect of a local
      promotional campaign on preconceptional lifestyle changes and the use of
      preconception care (PCC). MATERIAL AND METHODS: This quasi-comparative study was
      carried out between February 2015 and February 2016 at a community midwifery
      practice in the Netherlands. The intervention consisted of a dual track approach
      (i) a promotional campaign for couples who wish to conceive and (ii) a PCC
      pathway for health care providers. Questionnaires were collected from a sample of
      women who received antenatal care during the pre-intervention (n = 283) and post
      intervention (n = 257) period. Main outcome measures were preconceptional
      lifestyle changes and PCC use (defined as searching for information and/or
      consulting a health care provider). RESULTS: Women who were exposed to the
      intervention were significantly more likely to make at least one lifestyle change
      during the preconception period [adjusted OR 1.56 (95% CI 1.02-2.39)]. Women were
      especially more likely to preconceptionally reduce or quit [adjusted OR 1.72 (95%
      CI 1.05-2.83)] their alcohol consumption after exposure to the intervention.
      Although non-significant, it appeared that women who were exposed to the
      intervention more often prepared themselves for pregnancy by means of
      independently searching for preconception health information [adjusted OR 1.13
      (95% CI 0.77-1.65)] or consulting a health care provider regarding their wish to
      conceive [adjusted OR 1.24 (95% CI 0.81-1.92)]. CONCLUSIONS: Exposure to a local
      promotional campaign targeted at preconceptional health was associated with
      improved preconceptional lifestyle behaviours, especially with regard to alcohol
      consumption, and has the potential to improve the use of PCC.

PMID- 29377742
TI  - Novel compound heterozygous mutation in the POC1B gene underlie peripheral cone
      dystrophy in a Chinese family.
AB  - PURPOSE: To describe the clinical characteristics of a Chinese family with
      peripheral cone dystrophy (PCD) and identify the gene mutations causing PCD.
      METHODS: The Chinese PCD pedigree underwent comprehensive ophthalmic
      examinations, including visual acuity, slit lamp examination, fundoscopy, visual
      field examination, autofluorescence, fluorescence fundus angiography and
      indocyanine green angiography, full-field electroretinograms, and spectral-domain
      optical coherence tomography. The targeted next-generation sequencing of COD or
      cone-rod dystrophy (CORD) genes was used to identify the causative mutation.
      RESULT: The fundus characteristics of the Chinese patient were consistent with
      PCD. The novel compound heterozygous mutation, c.1354C>T and c.710A>G, in POC1B
      was identified in the patient, the mutations were segregated with the PCD
      phenotype in the family and were absent from ethnically matched control
      chromosomes. Prediction analysis demonstrated the novel missense mutation, POC1B
      c.710A>G, might be damaging. CONCLUSIONS: PCD was a type of COD or CORD and the
      novel compound heterozygous mutation in POC1B was responsible for PCD phenotype
      in the family.

PMID- 29377744
TI  - Misdiagnosis of X-linked retinitis pigmentosa in a choroideremia patient with
      heavily pigmented fundi.
AB  - Inherited retinal diseases are thought to be the leading cause of sight loss in
      the working age population. Mutations found in the RPGR and CHM genes cause
      retinitis pigmentosa (RP) and choroideremia, respectively. In the first instance,
      an X-linked family history of visual field loss commonly raises the suspicion of
      one of these two genes. In choroideremia, the classic description of a white
      fundal reflex secondary to the widespread chorioretinal degeneration was made
      over a hundred years ago in Caucasians. But, it is not so obvious in heavily
      pigmented fundi. Hence, the clinical diagnosis of CHM in non-Caucasian patients
      may be challenging in the first stages of the disease. Here we report a case of a
      Southeast Asian gentleman who has a family history of X-linked retinal
      degeneration and was found to have a confirmed in-frame deletion of 12 DNA
      nucleotides in exon 15 of the RPGR gene. Later in life, however, his fundal
      appearance showed unusual areas of circular pigment hypertrophy and clumping. He
      was therefore tested for carrying a disease-causing mutation in the CHM gene and
      a null mutation was found. Since gene therapy trials are ongoing for both of
      these conditions, it has now become critically important to establish the correct
      genetic diagnosis in order to recruit suitable candidates. Moreover, this case
      demonstrates the necessity to remain vigilant in the interpretation of genetic
      results which are inconsistent with clinical features.

PMID- 29377743
TI  - Leptin Upregulates Peripheral CD4+CXCR5+ICOS+ T Cells via Increased IL-6 in
      Rheumatoid Arthritis Patients.
AB  - CD4+CXCR5+ICOS+ T cells, known as Tfh (T Follicular helper) cells, are required
      for antibody production. Abnormal production and differentiation of Tfh cells are
      involved in many autoimmune diseases, including rheumatoid arthritis (RA). Leptin
      has the property of modulating immune system. Here, we explored the effect of
      leptin on CD4+CXCR5+ICOS+ T cells production in RA patients. Serum leptin levels
      were measured by enzyme-linked immunosorbent assay (ELISA). Peripheral blood
      mononuclear cells (PBMC) stimulated with CD3/CD28 were cultured in the presence
      and absence of leptin and with or without anti-IL-6 receptor (anti-IL-6R), anti
      IL-21R, and anti-IL-12R antibody respectively. IL-6, IL-21, and IL-12 levels were
      determined by ELISA. Bcl-6 was detected by reverse transcription-polymerase chain
      reaction. STAT1, pSTAT1, STAT3, and pSTAT3 were examined by western blot. We
      found that leptin levels were higher in RA patients than healthy controls. Leptin
      stimulated RA PBMC upregulated CD4+CXCR5+ICOS+ T cells, along with increased IL
      6, IL-21, and IL-12.CD4+CXCR5+ICOS+ T cells, Bcl-6 mRNA expression, pSTAT1, and
      pSTAT3 obviously declined when anti-IL-6R antibody was added into leptin-treated
      RA PBMC, which suggested that leptin upregulated RA CD4+CXCR5+ICOS+ T cells via
      increased IL-6 by activation of STAT1 and STAT3. We presented an innovative
      mechanism on how leptin participated in RA pathogenesis.

PMID- 29377745
TI  - Shoulder and elbow range of motion for the performance of activities of daily
      living: A systematic review.
AB  - The loss of range of motion (ROM) in the upper extremities can interfere with
      activities of daily living (ADL) and, therefore, many interventions focus on
      improving impaired ROM. The question, however, is what joint angles are needed to
      naturally perform ADL. The present review aimed to compile and synthesize data
      from literature on shoulder and elbow angles that unimpaired participants used
      when performing ADL tasks. A search was conducted in PubMed, Cochrane, Scopus,
      CINAHL, and PEDro. Studies were eligible when shoulder (flexion, extension,
      abduction, adduction) and/or elbow (flexion, extension) angles were measured in
      unimpaired participants who were naturally performing ADL tasks, and angles were
      provided per task. Thirty-six studies involving a total of 66 ADL tasks were
      included. Results demonstrated that unimpaired participants used up to full elbow
      flexion (150 degrees ) in personal care, eating, and drinking tasks. For shoulder
      flexion and abduction approximately 130 degrees  was necessary. Specific ADL
      tasks were measured often, however, almost never for tasks such as dressing. The
      synthesized information can be used to interpret impairments on the individual
      level and to establish rehabilitation goals in terms of function and prevention
      of secondary conditions due to excessive use of compensatory movements.

PMID- 29377746
TI  - Novel retinal findings in peroxisomal biogenesis disorders.
AB  - Peroxisomal biogenesis disorders are caused by disruption of long chain fatty
      acid metabolism due to mutations in PEX genes. Individuals with these disorders
      often have vision loss due to optic atrophy and pigmentary retinopathy. We report
      an unusual retinal manifestation of peroxisomal biogenesis disorder.

PMID- 29377747
TI  - Sex-Related Anemia Contributes to Disparities in Outcome of Patients Younger Than
      60 Years with ST-Elevation Myocardial Infarction.
AB  - BACKGROUND: Younger women with ST-segment elevation myocardial infarction (STEMI)
      have a worse outcome than their age-matched male peers. Our aim was to assess
      whether there are sex-based differences in anemia on admission, and if they are
      associated with the outcome of patients with STEMI younger than 60 years
      undergoing primary percutaneous coronary intervention (PCI). MATERIALS AND
      METHODS: Data of 2095 STEMI patients, 804 of whom were younger than 60 years,
      were analyzed. Data were analyzed using descriptive statistics. All-cause 30-day
      and 2-year mortality were documented. RESULTS: Women had a higher prevalence of
      anemia compared with men on admission (34.4% in women vs. 20.0% in men; p <
      0.0001). The 30-day mortality was similar in both groups (5.5% in women vs. 3.3%
      in men; p = 0.17). Anemia on admission, age, cardiogenic shock, and diabetes
      predicted higher 30-day mortality. Two-year mortality was higher in women (9.8%
      in women vs. 4.8% in men; p = 0.023). Anemia on admission, age, cardiogenic
      shock, and diabetes were identified as independent predictors of 2-year
      mortality. Sex was not associated with 30-day or 2-year mortality. CONCLUSIONS:
      We found sex-based differences in anemia on admission in STEMI patients younger
      than 60 years. Anemia, but not sex, was linked to 30-day and 2-year mortality.
      Anemia on admission in women younger than 60 years may help to explain the
      increased 2-year sex-related mortality in younger STEMI patients undergoing
      primary PCI.

PMID- 29377748
TI  - Long-term follow-up of autosomal dominant Stargardt macular dystrophy (STGD3)
      subjects enrolled in a fish oil supplement interventional trial.
AB  - BACKGROUND: Earlier studies have raised the notion that docosahexaenoic acid
      (DHA) and eicosapentaenoic acid (EPA) supplementation could be a useful
      intervention in autosomal dominant Stargardt macular dystrophy (STGD3). We sought
      to assess whether fish oil supplementation has a beneficial effect on the
      clinical course of STGD3 secondary to a mutation in the ELOVL4 gene. MATERIALS
      AND METHODS: Eleven patients with STGD3 were enrolled in an 8-year open-label,
      clinical interventional study of over-the-counter fish oil supplements at a
      recommended daily dose of 650 mg EPA and 350 mg DHA (NCT00420602). Subjects had
      annual eye examinations with complete imaging, visual function testing, and blood
      lipid analyses. Compliance with therapy was measured by periodic patient self
      report and with serum and red blood cell biomarkers of lipid consumption. Paired
      sample t-tests were used to measure differences in mean values of visual acuity,
      lipid biomarkers, and contrast sensitivity obtained at baseline and the last
      follow-up. RESULTS: All subjects showed progression of their maculopathy, and we
      could not discern a beneficial effect of the intervention. Compliance with the
      recommended fish oil supplement intervention was poor as assessed by patient self
      report and biomarkers of lipid consumption. CONCLUSIONS: Our inability to detect
      a benefit of fish oil could be the result of small subject numbers, poor
      compliance, or intervention too late in the course of the disease. We still
      advise STGD3 patients to consume fish or fish oil regularly, and we recommend
      that pre-symptomatic children with ELOVL4 mutations should be especially targeted
      for these interventions.

PMID- 29377749
TI  - The Fear of the Unknown Prevents Women from Participating in Clinical Trials.

PMID- 29377750
TI  - Tracking Outcomes of Snake Fungal Disease in Free-ranging Pygmy Rattlesnakes (
      Sistrurus miliarius).
AB  - Snake fungal disease (SFD) is caused by the fungus Ophidiomyces ophiodiicola and
      its documentation in wild snake populations has risen sharply in the past decade.
      Little is known regarding the fate of individual, free-ranging snakes afflicted
      with SFD. We monitored an afflicted population of pygmy rattlesnakes ( Sistrurus
      miliarius) at Lake Woodruff National Wildlife Refuge in Central Florida, US for 2
      yr. The severity of SFD in individual snakes was unrelated to the probability of
      their recapture later in the study, and half of the snakes diagnosed as severely
      infected at the onset of the study were recaptured later with no clinical signs
      of SFD. The clinical progress of 12 serially recaptured individuals also showed
      that individuals cleared the infection and fluctuated between no or low and
      severe clinical signs over the 2-yr study.

PMID- 29377751
TI  - A SEROLOGIC SURVEY OF PATHOGENS IN WILD BOAR ( SUS SCROFA) IN SWEDEN.
AB  - The wild boar ( Sus scrofa) population has increased markedly during the last
      three decades in Sweden and in other parts of Europe. This population growth may
      lead to increased contact between the wild boar and the domestic pig ( Sus scrofa
      scrofa), increasing the risk of transmission of pathogens. The objective of our
      study was to estimate the seroprevalence of selective pathogens, known to be
      shared between wild boars and domestic pigs in Europe, in three wild boar
      populations in Sweden. In total, 286 hunter-harvested female wild boars were
      included in this study. The sera were analyzed for antibodies against nine
      pathogens using different commercial or in-house enzyme-linked immunosorbent
      assays. Antibodies were detected against porcine parvovirus (78.0%), porcine
      circovirus type 2 (99.0%), swine influenza virus (3.8%), Erysipelothrix
      rhusiopathiae (17.5%), Mycoplasma hyopneumoniae (24.8%), and Toxoplasma gondii
      (28.6%). No antibodies were detected against porcine respiratory and reproductive
      syndrome virus, Brucella suis, or Mycobacterium bovis. Our results highlight the
      potential importance of the wild boar as a reservoir for pathogens potentially
      transmissible to domestic pigs and which also may affect human health.

PMID- 29377752
TI  - Babesia vesperuginis in Common Pipistrelle ( Pipistrellus pipistrellus) and the
      Bat Soft Tick Argas vespertilionis in the People's Republic of China.
AB  - Babesia vesperuginis was molecularly detected in 10% (5/48) of common pipistrelle
      bats ( Pipistrellus pipistrellus) in Shihezi City, Northwestern China.
      Interestingly, four bat ticks ( Argas vespertilionis), from Babesia DNA-positive
      common pipistrelle bats, were also positive for B. vesperuginis. Our findings
      extend the geographic range of the common pipistrelle bat as a reservoir of B.
      vesperuginis in Asia.

PMID- 29377753
TI  - Flight Versus Ground Out-of-hospital Rapid Sequence Intubation Success: a
      Systematic Review and Meta-analysis.
AB  - INTRODUCTION: Endotracheal intubation (ETI) is a critical procedure performed by
      both air medical and ground based emergency medical services (EMS). Previous work
      has suggested that ETI success rates are greater for air medical providers.
      However, air medical providers may have greater airway experience, enhanced
      airway education, and access to alternative ETI options such as rapid sequence
      intubation (RSI). We sought to analyze the impact of the type of EMS on RSI
      success. METHODS: A systematic literature search of Medline, Embase, and the
      Cochrane Library was conducted and eligibility, data extraction, and assessment
      of risk of bias were assessed independently by two reviewers. A bias-adjusted
      meta-analysis using a quality-effects model was conducted for the primary
      outcomes of overall intubation success and first-pass intubation success.
      RESULTS: Forty-nine studies were included in the meta-analysis. There was no
      difference in the overall success between flight and ground based EMS; 97% (95%
      CI 96-98) vs. 98% (95% CI 91-100), and no difference in first-pass success for
      flight compared to ground based RSI; 82% (95% CI 73-89) vs. 82% (95% CI 70-93).
      Compared to flight non-physicians, flight physicians have higher overall success
      99% (95% CI 98-100) vs. 96% (95% CI 94-97) and first-pass success 89% (95% CI 77
      98) vs. 71% (95% CI 57-84). Ground-based physicians and non-physicians have a
      similar overall success 98% (95% CI 88-100) vs. 98% (95% CI 95-100), but no
      analysis for physician ground first pass was possible. CONCLUSIONS: Both overall
      and first-pass success of RSI did not differ between flight and road based EMS.
      Flight physicians have a higher overall and first-pass success compared to flight
      non-physicians and all ground based EMS, but no such differences are seen for
      ground EMS. Our results suggest that ground EMS can use RSI with similar outcomes
      compared to their flight counterparts.

PMID- 29377754
TI  - Referral Practices Among U.S. Publicly Funded Health Centers That Offer Family
      Planning Services.
AB  - BACKGROUND: Referrals to other medical services are central to healthcare,
      including family planning service providers; however, little information exists
      on the nature of referral practices among health centers that offer family
      planning. MATERIALS AND METHODS: We used a nationally representative survey of
      administrators from 1,615 publicly funded health centers that offered family
      planning in 2013-14 to describe the use of six referral practices. We focused on
      associations between various health center characteristics and frequent use of
      three active referral practices. RESULTS: In the prior 3 months, a majority of
      health centers (73%) frequently asked clients about referrals at clients' next
      visit. Under half (43%) reported frequently following up with referral sources to
      find out if their clients had been seen. A third (32%) of all health centers
      reported frequently using three active referral practices. In adjusted analysis,
      Planned Parenthood clinics (adjusted odds ratio 0.55) and hospital-based clinics
      (AOR 0.39) had lower odds of using the three active referral practices compared
      with health departments, and Title X funding status was not associated with the
      outcome. The outcome was positively associated with serving rural areas (AOR
      1.39), having a larger client volume (AOR 3.16), being a part of an insurance
      network (AOR 1.42), and using electronic health records (AOR 1.62). CONCLUSIONS:
      Publicly funded family planning providers were heavily engaged in referrals.
      Specific referral practices varied widely and by type of care. More assessment of
      these and other aspects of referral systems and practices is needed to better
      characterize the quality of care.

PMID- 29377755
TI  - Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With
      Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial.
AB  - Purpose In the phase III METEOR trial ( ClinicalTrials.gov identifier:
      NCT01865747), 658 previously treated patients with advanced renal cell carcinoma
      were randomly assigned 1:1 to receive cabozantinib or everolimus. The
      cabozantinib arm had improved progression-free survival, overall survival, and
      objective response rate compared with everolimus. Changes in quality of life
      (QoL), an exploratory end point, are reported here. Patients and Methods Patients
      completed the 19-item Functional Assessment of Cancer Therapy-Kidney Symptom
      Index (FKSI-19) and the five-level EuroQol (EQ-5D-5L) questionnaires at baseline
      and throughout the study. The nine-item FKSI-Disease-Related Symptoms (FKSI-DRS),
      a subset of FKSI-19, was also investigated. Data were summarized descriptively
      and by repeated-measures analysis (for which a clinically relevant difference was
      an effect size >= 0.3). Time to deterioration (TTD) was defined as the earlier of
      date of death, radiographic progressive disease, or >= 4-point decrease from
      baseline in FKSI-DRS. Results The QoL questionnaire completion rates remained >=
      75% through week 48 in each arm. There was no difference over time for FKSI-19
      Total, FKSI-DRS, or EQ-5D data between the cabozantinib and everolimus arms.
      Among the individual FKSI-19 items, cabozantinib was associated with worse
      diarrhea and nausea; everolimus was associated with worse shortness of breath.
      These differences are consistent with the adverse event profile of each drug.
      Cabozantinib improved TTD overall, with a marked improvement in patients with
      bone metastases at baseline. Conclusion In patients with advanced renal cell
      carcinoma, relative to everolimus, cabozantinib generally maintained QoL to a
      similar extent. Compared with everolimus, cabozantinib extended TTD overall and
      markedly improved TTD in patients with bone metastases.

PMID- 29377756
TI  - Intravitreal Dexamethasone Implant for Postvitrectomy Macular Edema: A
      Retrospective Cohort of Patients with Postvitrectomy Macular Edema Treatment.
AB  - PURPOSE: To evaluate the clinical findings and the efficacy of dexamethasone
      intravitreal implant in patients with postvitrectomy macular edema. METHODS: The
      records of 14 patients diagnosed with postvitrectomy macular edema unresponsive
      to first-line treatment, treated with intravitreal dexamethazone implant
      injection and followed at least 6 months between October 2011 and May 2016 were
      retrospectively reviewed. All patients underwent standard ophtalmological
      examination, fluorescein angiography, and optical coherence tomography. Best
      corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular
      pressures (IOPs) were recorded at baseline, at first and sixth months after the
      injection. RESULTS: The mean BCVA, which was 0.2 +/- 0.14 logMAR at baseline
      significantly increased to 0.44 +/- 0.2 logMAR at first month (P = 0.05) and to
      0.4 +/- 0.22 logMAR at sixth month of intravitreal dexamethazone implant
      injection (P = 0.01). CMT was also significantly decreased to 368.3 +/- 90.4 MUm
      at first month and to 323 +/- 84.6 MUm at sixth month from pre-injection value of
      520.7 +/- 90.3 MUm (P = 0.001 and P = 0.002, respectively). IOP significantly
      increased from was 15 +/- 2.1 mmHg at baseline to 20.6 +/- 5.4 mmHg at first
      month of intravitreal dexamethazone implant injection (P = 0.01). CONCLUSION:
      Dexamethazone implant treatment may reduce CMT and improve BCVA in cases with
      postvitrectomy macular edema. IOP should be regularly screened in these cases.

PMID- 29377758
TI  - Levorphanol for Treatment of Intractable Neuropathic Pain in Cancer Patients.
AB  - Neuropathic pain in cancer patients is often difficult to treat, requiring a
      combination of several different pharmacological therapies. We describe two
      patients with complex neuropathic pain syndromes in the form of phantom limb pain
      and Brown-Sequard syndrome who did not respond to conventional treatments but
      responded dramatically to the addition of levorphanol. Levorphanol is a synthetic
      strong opioid that is a potent N-methyl-d-aspartate receptor antagonist, mu,
      kappa, and delta opioid receptor agonist, and reuptake inhibitor of serotonin and
      norepinephrine. It bypasses hepatic first-pass metabolism and thereby not
      subjected to numerous drug interactions. Levorphanol's unique profile makes it a
      potentially attractive opioid in cancer pain management.

PMID- 29377757
TI  - Contraceptive Method Use and Chlamydia Positivity Among California Family
      Planning Clients: The Case for New Multipurpose Prevention Technologies.
AB  - BACKGROUND: Adolescent girls and young women experience high rates of sexually
      transmitted infection (STI) with currently available contraceptive methods, yet
      few studies examine the burden of chlamydial infection by contraceptive method
      used. MATERIALS AND METHODS: In this cross-sectional analysis, we linked July
      2012-June 2013 claims from a publicly-funded family planning program in
      California to chlamydia laboratory test results. Female clients were classified
      by the most effective contraceptive method reported by providers during the year:
      tier 1 (high-efficacy permanent or long-acting reversible methods), tier 2
      (shorter-acting hormonal methods), or tier 3 (barrier methods, emergency
      contraception, or natural family planning). In addition, we identified clients
      who received condoms from providers. We used log-binomial models to estimate
      adjusted prevalence ratios comparing chlamydia positivity by contraceptive
      method(s). RESULTS: Of 74,636 female clients of ages 15-29 years with chlamydia
      test results, 5.1% had at least one positive test during the year. Chlamydia
      positivity was highest among tier 2 users (5.3%) compared with 4.5% and 4.9%
      among tiers 1 and 3 users, respectively (p < 0.001). Positivity was higher among
      clients who received condoms from providers than those who did not (6.3% vs.
      4.3%, p < 0.001). In adjusted analyses, there were no significant differences in
      positivity by contraceptive tier. However, clients who received condoms had 1.32
      (95% confidence interval: 1.24-1.40) times the positivity of those who did not.
      CONCLUSIONS: We found high chlamydia positivity among young female family
      planning clients regardless of contraceptive method. The development and
      provision of additional Multipurpose Prevention Technologies that confer
      protection against both pregnancy and STIs may help to address unmet need for STI
      prevention.

PMID- 29377759
TI  - Stability study of veterinary drugs in standard solutions for LC-MS/MS screening
      in food.
AB  - A study on stability of veterinary drugs in standard solutions stored at -80
      degrees C and at -20 degrees C was conducted over 1 year. Data were acquired on
      152 individual stock standard solutions and also on 15 family mixes and 2 working
      standard solutions. All solutions were prepared, stored and compared 1 year later
      against freshly prepared ones by LC-MS/MS. A statistical analysis was performed
      to set the acceptability criteria, taking into account the variability of
      standard preparations. In individual stock standard solutions stored at -80
      degrees C (12 months) and -20 degrees C (9 months), stability was demonstrated
      for 141 and 140 out of 152 compounds, i.e. for 92% and 93% of compounds,
      respectively. Drugs were even more stable when solubilised in either diluted
      family mixes or working standard solutions, with more than 99% and 94% of
      compounds found unaltered when stored at -80 degrees C and at -20 degrees C,
      respectively. In mixes, beta-lactams from the cephalosporin (cefadroxil and
      cephalexin) and penicillin (amoxicillin and ampicillin) families were found to be
      the least stable compounds when stored at -20 degrees C (6 months), necessitating
      storage at -80 degrees C to achieve a 1-year shelf life. The study also evidenced
      solubility issues for two sulfonamides (sulfadiazine and sulfamerazine) in
      methanol-based solutions. An independent stability study conducted by a second
      laboratory confirmed the 1-year stability of 3 family mixes-quinolones,
      sulfonamides and tetracyclines.

PMID- 29377760
TI  - Prevalence of Self-Reported Diabetes by Sexual Orientation: Results from the 2014
      Behavioral Risk Factor Surveillance System.
AB  - PURPOSE: This study aimed to compare the prevalence of self-reported diabetes and
      diabetes risk factors among adult sexual minority and heterosexual populations in
      the United States. METHODS: Data from the 2014 Behavioral Risk Factor
      Surveillance System for 3776 lesbian, gay, and bisexual (LGB) adults and 142,852
      heterosexual adults aged 18 years and older were used to estimate the prevalence
      of diabetes. Binomial logistic regression models were used to compare the odds of
      diabetes by sexual orientation. RESULTS: Sexual minorities were younger and more
      racially diverse than heterosexuals. Gay men less often and lesbian and bisexual
      women more often reported a body mass index of 30 kg/m2 or higher than
      heterosexuals. Overall, 14.2% of bisexual men, 11.4% of gay men, and 10.8% of
      heterosexual men reported a lifetime diabetes diagnosis, as did 8.5% of lesbian
      women, 5.7% of bisexual women, and 10.2% of heterosexual women. After controlling
      for multiple factors, gay (odds ratio [OR] = 1.50; confidence interval [95% CI] =
      1.09-2.07) and bisexual men [OR = 1.55; 95% CI = 1.00-2.07] were more likely to
      report a lifetime diabetes diagnosis than heterosexual men. Similar differences
      were not found for lesbian [OR = 1.22; 95% CI = 0.76-1.95] or bisexual women [OR
      = 0.88; 95% CI = 0.62-1.26]. CONCLUSION: Sexual minorities may be at increased
      risk for diabetes than their heterosexual peers. This may be due partly to the
      chronic stressors associated with being a member of a marginalized population.
      Future research should explore the underlying causes and consequences of LGB
      diabetes disparities and elucidate best practices to improve diabetes screening
      and care for these vulnerable patient populations.

PMID- 29377761
TI  - Ozone treatment to reduce deoxynivalenol (DON) and zearalenone (ZEN)
      contamination in wheat bran and its impact on nutritional quality.
AB  - Wheat bran is an important source for human and animal feed. Its nutritional
      aspects include a high content of fibre and minerals, as well as phenolic
      compounds that help prevent chronic diseases. However, wheat can be susceptible
      to contamination by fungus, which can produce mycotoxins such as deoxynivalenol
      (DON) and zearalenone (ZEN), causing adverse health effects. Therefore, methods
      should be developed to reduce possible contamination. Ozone can be used for this
      purpose as it is considered safe and environmental friendly. The aim of this
      study was to evaluate the reduction of DON and ZEN concentrations in wheat bran
      using the ozonation process as well as to evaluate the effect of ozonation on the
      nutritional quality of bran. Considering this, wheat bran naturally contaminated
      with both DON and ZEN was processed using ozone at different conditions. The
      nutritional quality of the bran was evaluated after processing considering the
      following aspects: the total phenolic content and the bran antioxidant capacity
      (by using both DPPH and ABTS radicals). The results showed that the degradation
      of ZEN was higher and faster than the degradation of DON, which could be
      explained by their molecular structures. The total phenolic content and
      antioxidant capacity of the bran were not affected by the ozonation process,
      which is preferable from a nutritional point of view. Therefore, ozonation was
      demonstrated to be a possible method for reducing mycotoxins in wheat bran,
      although more studies are needed in order to better understand and optimise
      processing and product quality.

PMID- 29377762
TI  - They Can Handle the Stress: MPK17 and PMD1 act in a salt-specific pathway.
AB  - Arabidopsis MAP KINASE17 (MPK17) was recently identified as a novel regulator of
      peroxisome division in response to salt stress. Further, the known peroxisome
      division factor PEROXISOME AND MITOCHONDRIAL DIVISION FACTOR1 (PMD1) genetically
      acts downstream of MPK17. We previously showed that mutants defective in either
      MPK17 or PMD1 fail to proliferate peroxisomes in response to NaCl stress. Here,
      we show that, unlike their abnormal NaCl responses, mpk17 and pmd1 mutants
      display wild type responses to other stresses known to alter peroxisome
      proliferation, suggesting that plants distinguish among peroxisome division
      inducing stresses and alter the peroxisome division pathway based on the stress
      applied.

PMID- 29377764
TI  - Dietary Fiber, C-Reactive Protein, and Leisure-Time Physical Activity Among U.S.
      Adults.
AB  - BACKGROUND: Some evidence suggests an inverse association between increased fiber
      intake and C-reactive protein (CRP). However, few studies have examined the
      associations among CRP, dietary fiber, and leisure-time physical activity (LTPA)
      in a nationally representative sample of U.S. adults. METHODS: Sample (n = 8372)
      included adults (>=20 years of age) who participated in the 2007-2010 National
      Health and Nutrition Examination Survey. Tertiles of reported fiber intake were
      created. The dependent variable was elevated CRP (>3-10 mg/L). Logistic
      regression models were stratified by LTPA participation and adjusted for age,
      gender, race, waist circumference (WC), and standing height. RESULTS: In adults
      reporting any volume of LTPA participation, increased fiber intake was
      significantly (P < 0.05 for the upper tertile of fiber intake) associated with
      lower odds of having an elevated CRP concentration when compared with the lowest
      tertile. Similar associations were not revealed in analyses limited to adults
      reporting no LTPA participation. After additional adjustment for WC and standing
      height, this protective association was no longer statistically significant.
      CONCLUSIONS: Results suggest that WC and standing height may mediate the
      beneficial association between increased fiber intake and lower odds of elevated
      CRP in adults reporting LTPA participation.

PMID- 29377763
TI  - EGFRvIII expression triggers a metabolic dependency and therapeutic vulnerability
      sensitive to autophagy inhibition.
AB  - Expression of EGFRvIII is frequently observed in glioblastoma and is associated
      with increased cellular proliferation, enhanced tolerance to metabolic stresses,
      accelerated tumor growth, therapy resistance and poor prognosis. We observed that
      expression of EGFRvIII elevates the activation of macroautophagy/autophagy during
      starvation and hypoxia and explored the underlying mechanism and consequence.
      Autophagy was inhibited (genetically or pharmacologically) and its consequence
      for tolerance to metabolic stress and its therapeutic potential in (EGFRvIII+)
      glioblastoma was assessed in cellular systems, (patient derived) tumor
      xenopgrafts and glioblastoma patients. Autophagy inhibition abrogated the
      enhanced proliferation and survival advantage of EGFRvIII+ cells during stress
      conditions, decreased tumor hypoxia and delayed tumor growth in EGFRvIII+ tumors.
      These effects can be attributed to the supporting role of autophagy in meeting
      the high metabolic demand of EGFRvIII+ cells. As hypoxic tumor cells greatly
      contribute to therapy resistance, autophagy inhibition revokes the radioresistant
      phenotype of EGFRvIII+ tumors in (patient derived) xenograft tumors. In line with
      these findings, retrospective analysis of glioblastoma patients indicated that
      chloroquine treatment improves survival of all glioblastoma patients, but
      patients with EGFRvIII+ glioblastoma benefited most. Our findings disclose the
      unique autophagy dependency of EGFRvIII+ glioblastoma as a therapeutic
      opportunity. Chloroquine treatment may therefore be considered as an additional
      treatment strategy for glioblastoma patients and can reverse the worse prognosis
      of patients with EGFRvIII+ glioblastoma.

PMID- 29377766
TI  - High occurrence rates of enrofloxacin and ciprofloxacin residues in retail
      poultry meat revealed by an ultra-sensitive mass-spectrometric method, and
      antimicrobial resistance to fluoroquinolones in Campylobacter spp.
AB  - An ultra-sensitive mass spectrometric confirmation and quantification method for
      the determination of selected fluoroquinolones-enrofloxacin and its main
      metabolite ciprofloxacin-was developed and validated in poultry meat samples. The
      achieved limits of quantification were 1 ng kg-1 for enrofloxacin and 10 ng kg-1
      for ciprofloxacin. The analysis of 40 retail poultry samples originating from
      Estonia, Latvia, Lithuania, Poland and France revealed that 93% of samples
      contained residues of enrofloxacin in the range from 3.3 to 1126 ng kg-1.
      Previous studies have shown high levels of antimicrobial resistance to
      fluoroquinolones, particularly in Campylobacter spp. and various faecal
      indicators isolated from broiler meat. Consequently, the revealed widespread
      usage of fluoroquinolones in the poultry industry may result in the further
      emergence of antimicrobial resistance of Campylobacter in the food chain.

PMID- 29377765
TI  - Autophagy contributes to sulfonylurea herbicide tolerance via GCN2-independent
      regulation of amino acid homeostasis.
AB  - Sulfonylurea (SU) herbicides inhibit branched-chain amino acid (BCAA)
      biosynthesis by targeting acetolactate synthase. Plants have evolved target-site
      resistance and metabolic tolerance to SU herbicides; the GCN2 (general control
      non-repressible 2) pathway is also involved in SU tolerance. Here, we report a
      novel SU tolerance mechanism, autophagy, which we call 'homeostatic tolerance,'
      is involved in amino acid signaling in Arabidopsis. The activation and reversion
      of autophagy and GCN2 by the SU herbicide tribenuron-methyl (TM) and exogenous
      BCAA, respectively, confirmed that TM-induced BCAA starvation is responsible for
      the activation of autophagy and GCN2. Genetic and biochemical analyses revealed a
      lower proportion of free BCAA and more sensitive phenotypes in atg5, atg7, and
      gcn2 single mutants than in wild-type seedlings after TM treatment; the lowest
      proportion of free BCAA and the most sensitive phenotypes were found in atg5 gcn2
      and atg7 gcn2 double mutants. Immunoblotting and microscopy revealed that TM
      induced activation of autophagy and GCN2 signaling do not depend on the presence
      of each other, and these 2 pathways may serve as mutually compensatory mechanisms
      against TM. TM inhibited the TOR (target of rapamycin), and activated autophagy
      in an estradiol-induced TOR RNAi line, suggesting that TM-induced BCAA starvation
      activates autophagy, probably via TOR inactivation. Autophagy and GCN2 were also
      activated, and independently contributed to TM tolerance in plants conferring
      metabolic tolerance. Together, these data suggest that autophagy is a proteolytic
      process for amino acid recycling and contributes to GCN2-independent SU
      tolerance, probably by its ability to replenish fresh BCAA.

PMID- 29377767
TI  - Dietary exposure to cadmium of Shenzhen adult residents from a total diet study.
AB  - Cadmium (Cd) contamination has become a public health concern in recent decades.
      The aim of the present study was to assess the contribution of dietary Cd
      exposure and its health risk among Shenzhen adult residents using the Total Diet
      Study (TDS) approach. Cd was determined in 13 food groups using 276 individual
      samples by ICP-MS. The major food contributors to Cd exposure of Shenzhen adult
      residents were 'Vegetables' (32.6% of the total exposure), 'Rice and its
      products' (19.2% of the total exposure) and 'Fish, seafood and shellfish' (18.5%
      of the total exposure). The mean and the 95th percentile dietary exposure to Cd
      of Shenzhen adults were 9.9 and 13 MUg kg-1 bw month-1, respectively. The dietary
      exposures of all individual age-gender population subgroups were below the
      provisional tolerable monthly intake (PTMI = 25 MUg kg-1 bw month-1), so the
      health risk of Cd dietary exposure of Shenzhen adults is considered to be low,
      but still, cadmium pollution should be strictly controlled and monitored
      continuously due to an exceptionally long biological half-life of cadmium.

PMID- 29377768
TI  - Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using
      Anti-Human Podoplanin Monoclonal Antibody Panel.
AB  - Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in
      several normal tissues and malignant tumors. Although PDPN expression in
      rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other
      arthritic conditions has not been fully elucidated. In this study, we examined
      PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN)
      monoclonal antibody (mAb) panel to select the most useful one for evaluation of
      synovitis. Synovial tissue samples were obtained from 11 RA patients and 9
      osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were
      immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab
      12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell
      counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry
      showed that PDPN was markedly expressed in both macrophage-like type A and
      fibroblast-like type B lining cells of the hyperplastic synovial lining cell
      layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs,
      LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression
      was also detectable. Although LpMab-12 also showed the highest score in OA, the
      difference was not statistically significant. The inflammatory synovitis score of
      RA was significantly higher than that of OA. PDPN was expressed in inflammatory
      lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN
      antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA
      synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific
      biomarker for evaluating synovitis in RA and inflammatory OA.

PMID- 29377769
TI  - Using Epidemiological Principles to Explain Fungicide Resistance Management
      Tactics: Why do Mixtures Outperform Alternations?
AB  - Whether fungicide resistance management is optimized by spraying chemicals with
      different modes of action as a mixture (i.e., simultaneously) or in alternation
      (i.e., sequentially) has been studied by experimenters and modelers for decades.
      However, results have been inconclusive. We use previously parameterized and
      validated mathematical models of wheat Septoria leaf blotch and grapevine powdery
      mildew to test which tactic provides better resistance management, using the
      total yield before resistance causes disease control to become economically
      ineffective ("lifetime yield") to measure effectiveness. We focus on tactics
      involving the combination of a low-risk and a high-risk fungicide, and the case
      in which resistance to the high-risk chemical is complete (i.e., in which there
      is no partial resistance). Lifetime yield is then optimized by spraying as much
      low-risk fungicide as is permitted, combined with slightly more high-risk
      fungicide than needed for acceptable initial disease control, applying these
      fungicides as a mixture. That mixture rather than alternation gives better
      performance is invariant to model parameterization and structure, as well as the
      pathosystem in question. However, if comparison focuses on other metrics, e.g.,
      lifetime yield at full label dose, either mixture or alternation can be optimal.
      Our work shows how epidemiological principles can explain the evolution of
      fungicide resistance, and also highlights a theoretical framework to address the
      question of whether mixture or alternation provides better resistance management.
      It also demonstrates that precisely how spray tactics are compared must be given
      careful consideration. [Formula: see text] Copyright (c) 2018 The Author(s). This
      is an open access article distributed under the CC BY 4.0 International license .

PMID- 29377770
TI  - Environmental dependency phenomena in schizophrenia: a pilot study.
AB  - INTRODUCTION: Environmental dependency phenomena refer to the enslavement of
      patients' performances under the characteristics of the tasks and were first
      described in case of prefrontal lobe damage. Two forms of environmental
      dependency, executive and social, may be dissociated, which involve respectively
      dorsolateral and orbital prefrontal cortex (PFC) dysfunction. Schizophrenia is
      widely considered to be caused by PFC dysfunction, but no study to date has
      addressed environmental dependency in this pathology. METHODS: We compared
      patients (N = 17) and healthy controls (N = 28) on a task dedicated to the study
      of environmental dependency. RESULTS: Our results demonstrate the presence of
      environmental dependency in schizophrenia. Each form of environmental dependency
      can be highlighted independently, as previously demonstrated by studies with
      prefrontal patients. CONCLUSIONS: These findings suggest specific prefrontal
      dysfunction for each subgroup of patients and demonstrate a dissociation between
      socio-cognitive and neurocognitive performance in schizophrenia. Additionally, we
      found relationships between symptomatology and environmental dependency. This
      pilot study supports the relevance of studying environmental dependency to
      highlight specific patterns of prefrontal disorders in schizophrenia, which may
      contribute to a better understanding of PFC dysfunction in schizophrenia.

PMID- 29377771
TI  - Physical Activity, Body Mass Index, and Clustered Metabolic Risk in U.S.
      Adolescents: 2007-2012 Nhanes.
AB  - BACKGROUND: While studies to date have shown that children and adolescents who
      meet the current physical activity (PA) recommendations and maintain a healthy
      body weight demonstrate significantly lower cardiometabolic risk, there are some
      studies that suggest that the relationship between PA and metabolic risk may be
      mediated by adiposity. The aim of the present study was to examine variation in
      clustered metabolic risk (cMetS) in adolescents classified as not
      overweight/active (NOA), not overweight/not active (NONA), overweight/active
      (OA), and overweight/not active (ONA). METHODS: The sample included adolescent
      participants (n = 875; 12-17 years) of the 2007-2012 National Health and
      Nutrition Examination Survey (NHANES). The cMetS score included triglycerides,
      high-density lipoprotein cholesterol, fasting plasma glucose, and mean arterial
      pressure. Age- and sex-specific body mass index (BMI) percentiles were utilized;
      overweight was defined as BMI percentile >=85th. Activity data included self
      reported frequency of moderate-to-vigorous PA. Adolescents reporting >=60 min/day
      of PA were considered "active." General linear models, adjusted for age, sex, and
      race-ethnicity, were used. A 6-year fasting sample weight was applied to the
      analyses to ensure representativeness of the data. RESULTS: The cMetS scores were
      significantly (P < 0.05) higher in OA and ONA adolescents compared to NOA (beta =
      1.08 and beta = 1.57, respectively). In ONA males, cMetS was significantly (P <
      0.01) higher compared to NOA males. In OA and ONA females, cMetS scores were
      significantly higher compared to the referent group (P < 0.01 for both).
      CONCLUSIONS: The cMetS scores were increased in overweight adolescents compared
      to those who were not overweight, regardless of their reported activity level.

PMID- 29377772
TI  - Assessment of mumps-containing vaccine effectiveness during an outbreak:
      Importance to introduce the 2-dose schedule for China.
AB  - INTRODUCTION: China has used 3 different mumps-containing vaccines (MuCV) since
      1990: monovalent mumps vaccine, measles-mumps (MM) vaccine, and measles-mumps
      rubella (MMR) vaccine, and one dose MuCV (using MMR at 18 months) has been
      included in the EPI since 2007. MuCV effectiveness has been of concern following
      large-scale mumps outbreaks. In 2015, an outbreak of mumps occurred in a primary
      school, which allow us assess vaccine effectiveness of different MuCVs. METHOD:
      All children in the school were studied as a retrospective cohort. Vaccination
      histories and case information were obtained from vaccination records and
      clinic/hospital logs. Parental questionnaires were used to confirm students'
      illnesses and calculate attack rate (AR). VE was assessed using the formula, VE =
      (AR in unvaccinated students- AR in the vaccinated students) / (AR in
      unvaccinated students). VEs of different type of MuCV were compared. RESULTS: In
      total, 283 students were identified as clinical mumps among the 2370 students,
      and 1908 students were included for MuCV VE assessment. 213 (including 21 [8.9%]
      patients) were 2-dose MuCV recipients (AR: 9.9%), 1165 (including 123 [51.9%]
      patients) were 1-dose recipients (AR: 10.6%), and 530 (including 93 [39.2%]
      patients) were unvaccinated (AR: 17.5%). VE was 44% for 2 doses and 40% for one
      dose. For one-MuCV-dose students, estimated mumps VE was 63% for vaccinated
      within 3 years (between vaccination and this outbreak); 50% for vaccinated within
      3 to 5 years; and 34% for vaccinated more than 5 years. Comparing VE by vaccine
      type and 5-year interval since vaccination, VE for MMR was 60%, which was
      consistently higher than VE for monovalent mumps vaccine (22%) and MM (2%).
      CONCLUSION: This outbreak was associated with low and declining 1-dose MuCV
      effectiveness. China's immunization program should evaluate the potential of a 2
      dose MMR schedule to adequately control mumps.

PMID- 29377773
TI  - Patient-Targeted Googling by New Zealand Mental Health Professionals: A New Field
      of Ethical Consideration in the Internet Age.
AB  - BACKGROUND: Patient-targeted Googling (PTG) describes the searching on the
      Internet by healthcare professionals for information about patients with or
      without their knowledge. INTRODUCTION: Little research has been conducted into
      PTG internationally. PTG can have particular ethical implications within the
      field of mental health. This study was undertaken to identify the extent of PTG
      by New Zealand mental healthcare professionals and needs for further guidance
      regarding this issue. MATERIALS AND METHODS: All (1,850) psychiatrists, clinical
      psychologists, and psychotherapists working in New Zealand were electronically
      surveyed about their experience of PTG and knowledge about the associated
      practice of therapist-targeted Googling (TTG) using a questionnaire that had
      previously been developed with a German sample. Due to ethics and advertising
      restrictions, only one indirect approach was made to potential participants.
      RESULTS: Eighty-eight clinicians (5%) responded to the survey invitation. More
      than half (53.4%, N = 47) of respondents reportedly being engaged in PTG, but
      only a minority (10.3%, N = 9) had ever received any education about the subject.
      Reasons for undertaking PTG included facilitating the therapeutic process,
      information being in the public domain, and mitigating risks. Reasons against
      undertaking PTG included impairment of therapeutic relationship, unethical
      invasion of privacy, and concerns regarding the accuracy and clinical relevance
      of online information. Two-thirds of participants reported being the subject of
      TTG. DISCUSSION: New Zealand psychiatrists, clinical psychologists, and
      psychotherapists are engaging in PTG with limited education and professional
      guidance. Further discussion and research are required, and so, PTG is undertaken
      in a manner that is safe and useful for patients and health practitioners.

PMID- 29377774
TI  - My Own Best Friend: Homeless Youths' Hesitance to Seek Help and Strategies for
      Coping Independently after Distressing and Traumatic Experiences.
AB  - Although homeless youth face extreme adversities, they are often hesitant to seek
      help from formal and informal supports. The current study qualitatively explored
      homeless youths' reasons for coping independently and their strategies for doing
      so. Youth accessing services (N = 145) in three U.S. cities were interviewed
      about their rationales for not seeking help from others regarding distressing
      experiences. Analyses illustrated specific barriers to help seeking that prompted
      homeless youth to cope on their own by utilizing soothing, avoidant, aggressive,
      and introspective coping strategies. Implications for outreaching to those least
      likely to seek help are discussed.

PMID- 29377775
TI  - Moderating Effects of Prevention-Focus on the Paths from Two Insecure Attachment
      Dimensions to Depression.
AB  - The present study investigated the moderating effects of prevention-focus on the
      paths from the dimensions of insecure attachment (attachment avoidance and
      attachment anxiety) to depression. Two hundred twenty eight Korean college
      students completed the Experience in Close Relationship - Revised Scale; the
      Regulatory Focus Strategies Scale; and the Center for Epidemiologic Studies
      Depression Scale. Results revealed a significant moderating effect for prevention
      focus on the path from attachment avoidance to depression, but not on the path
      from attachment anxiety to depression. They further suggest that different
      interventions are needed for different combinations of persons' insecure
      attachment dimensions and levels of prevention-focus. Counseling implications and
      suggestions for future research are discussed.

PMID- 29377776
TI  - The Effect of Vision and Surface Compliance on Balance in Untrained and Strength
      Athletes.
AB  - The purpose of this investigation was to evaluate the effect of the removal of
      vision and/or surface compliance on postural stability in strength athletes who
      habitually use free-weights and compound movements in their training (i.e.,
      powerlifters, Olympic weightlifters), and untrained individuals. Static and
      dynamic balance testing was performed with eyes open or closed on stable and
      memory foam surfaces. Both groups had similar increases in postural sway area and
      velocity during quiet standing testing; whereas group main effects and
      interactions for dynamic testing revealed that untrained participants experienced
      greater relative declines in postural performance when voluntary limits of
      stability are stressed, especially when both vision and surface compliance were
      deterred. These results demonstrate that in comparison to untrained young adults,
      postural control variables may be reduced to a lesser extent in strength athletes
      when sensory constraints are altered; however this appears to be specific to the
      type of postural task performed.

PMID- 29377777
TI  - Movement Speed and Accuracy in Space and Time: The Complementarity of Error
      Distributions.
AB  - Movement speed-accuracy trade-off is a function of the space-time constraints of
      the task. We investigated the space-time account of Hancock and Newell (1985) and
      the hypothesis of complementarity between the four moments of the error
      distribution in space and time. Twelve participants performed 15 conditions in a
      line drawing task composed of different spatial (10, 20, and 30 cm) and temporal
      (250 to 2,500 ms) criteria. The results showed that all moments of distributions
      changed systematically between conditions but there were some departures from the
      Hancock and Newell predictions. In contrast, individual analysis revealed the
      complementarity of the spatial and temporal error including a trade-off between
      the four moments of error. These findings support a complementary space-time
      account of movement speed and accuracy.

PMID- 29377778
TI  - Bio-psycho-social-spiritual needs of adolescents and young adults with life
      threatening illnesses: Implications for social work practice.
AB  - This paper explores the biopsychosocial and spiritual needs of adolescents and
      young adults (AYA) with life-threatening or terminal illnesses. AYA are situated
      between childhood and adulthood (ages 15-25) and have distinct biopsychosocial
      and spiritual needs unique to their developmental stage. Having a life
      threatening or terminal illness directly challenges normal AYA developmental
      tasks and identity formation. AYA experience more troubling physical symptoms
      during the dying process compared to other age groups, which leads to significant
      psychological distress and an increased need for pharmacological treatments. In
      general, AYA desire to be fully informed and involved in the health care decision
      making process, leading to ethical dilemmas when the AYA is a minor and their
      wishes differ from the wishes of their legal guardian(s). Social workers are
      especially well-equipped to serve this population due to aligning professional
      standards and ability to advocate for holistic care within interdisciplinary
      teams. Additional research is needed to tailor holistic interventions to meet the
      needs of this population.

PMID- 29377779
TI  - A Short Measure of the Revised Reinforcement Sensitivity Theory - RSQ17.
AB  - The need for a research and practical tool, such as a short, reliable, and valid
      personality assessment test, suggests researchers to create shortened versions of
      original instruments. Reinforcement sensitivity questionnaire (RSQ) was created
      in line with some basic premises of revised Reinforcement sensitivity theory,
      which proposes three motivational and emotional systems: Behavioral inhibition
      system (BIS), responsible for scanning environment for potential threats,
      Behavioral activation system (BAS), responsible for aproaching behavior, and the
      Fight/Flight/Freeze system (FFFS), responsible for behavior in the present
      threat. RSQ comprises five scales: BIS, BAS, Fight, Flight, and Freeze. The aim
      of this study was to develop a short version of RSQ, which would be beneficial to
      both research and practical purposes. Item response theory analyses were used for
      item selection. The study comprised two samples of participants, whereby Sample 1
      (N = 837, 34.6% male, aged 18 - 82, M = 31.63, SD = 13.54) served as the
      derivation sample, while Sample 2 (818 participants, 43.6% male, 18-75 years, M =
      29.65, SD = 12.52) served as validation sample. Factorial validity of the short
      RSQ was examined on both Sample 1 and Sample 2. Convergent and divergent validity
      of the short RSQ was examined using RST-PQ, Jackson-5, BIS/BAS scales, and Big
      Five Inventory. The results point to satisfactory internal consistency, factorial
      validity, and construct validity of the short RSQ, suggesting that it is an
      adequate measure for research settings or other contexts which require the use of
      short personality questionnaires.

PMID- 29377780
TI  - Facing an aging society: Taiwan's universities in crisis.
AB  - As a result of the phenomenon of a rapidly aging population and low birth rates,
      Taiwanese universities face a shortage of traditionally aged students and as a
      result must respond to older learners' needs. In response to this demand, the
      Ministry of Education issued the Lifelong Learning Act in 2002 and White Paper
      for implementing education for older persons in an aging society in 2006.
      Universities now face unprecedented challenges as they play a leading role in
      facilitating these programs. The purpose of this article is to explore the
      challenges Taiwanese universities face in educating an aging society and to
      provide some suggestions. First, this article notes current challenges. Second,
      the development of the status quo of senior education is presented. Third, the
      changing landscape of universities is discussed. Finally, some suggestions are
      presented for both university administration and program developers. In
      conclusion, universities should grasp this opportunity to modify strategies for
      involving older adults.

PMID- 29377781
TI  - Older bisexual people: Implications for social work from the 'Looking Both Ways'
      study.
AB  - There is a growing social work literature about lesbian, gay, bisexual, and
      transgender (LGBT) older people. However, research and guidance are predominantly
      based on the experiences of older gay men and, to a lesser extent, older
      lesbians. There is little to help practitioners work with older bisexual people.
      The Looking Both Ways study aimed to contribute to this gap in knowledge. We
      undertook in-depth purposely sampled qualitative interviews with 12 people aged
      over 50, all of whom have bisexual relationship histories and half of whom also
      currently identify as bisexual. There were three main findings. First, biphobia
      (prejudice against bisexual people) impacts on older people with bisexual
      histories in ways that may affect their well-being in later life. Second,
      concerns around receiving care are similar in some ways and different in others
      from the concerns of lesbians and gay men. Third, people with bisexual
      relationship histories may have developed strong support networks and resilience,
      factors that may be very beneficial in later life. Three recommendations for
      social work professionals were identified: 1) understand biphobia, 2) recognize
      the legitimacy of concerns about receiving care, and 3) ask about support
      networks rather than assuming family support.

PMID- 29377782
TI  - Motivation to volunteer among senior center participants.
AB  - Senior centers in the United States play a vital role in the aging continuum of
      care as the focal points of a community-based system of services targeting
      independent older adults to promote their social integration and civically
      engagement. Although several studies have evaluated the diversity of senior
      center programs, demographic characteristics of participants, and benefits of
      participation, very few have explored motivations to volunteer among
      participants. Many senior centers rely on a cadre of participants who volunteer
      there to assist with programs and meal services. However, a systematic
      examination of volunteering interests and the rationale for volunteering among
      senior center participants has been missing from the literature. This mixed
      methods study, conducted at a large suburban senior center, explores the
      interests and motivations of volunteerism among the participants. The study found
      that there was limited interest in volunteering among senior center participants.
      Those who were motivated to volunteer wanted to do so in order to stay connected
      with their community. There was strong interest in volunteering for single events
      or projects rather than a long-term commitment. Implications for senior centers
      are discussed.

PMID- 29377784
TI  - Editorial 2018 for Ocular Immunology and Inflammation.

PMID- 29377783
TI  - Diagnosis of Cytomegalovirus Anterior Uveitis in Two European Referral Centers.
AB  - PURPOSE: To evaluate diagnostic methods and clinical signs of CMV anterior
      uveitis (AU), a rarely described entity in Europe. METHODS: We included patients
      with clinical characteristics of CMV AU and positive PCR and/or Goldmann-Witmer
      coefficient (GWc) for CMV. RESULTS: We report 21 patients with unilateral uveitis
      (100%) and signs of Posner-Schlossman syndrome (PSS) (n = 20, 95.2%), Fuchs
      uveitis syndrome (FUS) (n = 1, 4.7%), and endotheliitis (n = 4, 19,04%). PCR was
      positive in 15/21 (71.4%) and GWc in 8/9 patients (88.9%) in aqueous for CMV. GWc
      was the only positive test in 6/9 patients (66,6%). When PCR alone was performed
      (without GWc) in the first tap, repeated aqueous taps were needed, twice in five
      cases and thrice in one case. CONCLUSION: Combining PCR and GWc were very helpful
      to confirm the clinical diagnosis of CMV AU. In case of very high clinical
      suspicion and negative results, repeated tap seems to be recommended.

PMID- 29377786
TI  - Intercellular communication of DNA damage and oxidative status underpin bystander
      effects.
AB  - PURPOSE: A well-known phenomenon in the field of radiation biology is that cells
      exposed to ionizing radiation (IR) (targeted cells) can induce in non-irradiated
      (non-targeted), bystander cells effects reminiscent of DNA damage responses (DDR)
      normally expected, exclusively in targeted cells. These phenomena are
      collectively referred to as radiation-induced bystander effects (RIBE) and have
      different manifestations depending on the endpoint studied. Although it is now
      recognized that RIBE reflects to a considerable extent communication by the
      targeted cells to undamaged cells of their damaged status, the molecular
      underpinnings of this communication and its significance for the organism are
      only partly understood. In particular, it remains unknown why and how targeted
      cells induce DNA damage in non-targeted, bystander cells threatening their
      genomic stability and risking thus their transformation to cancer cells. Here, we
      outline observations hinting to possible sources of artifacts in experiments
      designed to detect RIBE and summarize a model according to which targeted cells
      modulate their redox status as part of their overall response to IR and use this
      modified redox status as a source to generate signals that are transmitted to non
      irradiated cells of the organism. MATERIAL AND METHODS: A synthesis of published
      evidence is presented. RESULTS: Depending on type, RIBE signals may be
      transmitted through various forms of direct intercellular contact, through
      molecules acting locally in a paracrine fashion, or through molecules acting
      remotely in an endocrine fashion. We reason that DNA damage generated in
      bystander cells is unlikely to manifest the clustered character exhibited in
      directly exposed cells and postulate that RIBE will depend on complications
      generated when simpler forms of damage encounter the DNA replication fork.
      CONCLUSIONS: We suggest that RIBE result from intercellular communication
      mechanisms designed to spread within tissues, or the organism, alarm signals of
      DNA damage inflicted in subsets of the constituent cells. This response likely
      evolved to protect organisms by appropriately modulating stress response, repair
      or apoptosis, and may in some instances also cause adverse effects, e.g. as
      collateral damage.

PMID- 29377787
TI  - The Role of Experimenter Belief in Social Priming.
AB  - Research suggests that stimuli that prime social concepts can fundamentally alter
      people's behavior. However, most researchers who conduct priming studies fail to
      explicitly report double-blind procedures. Because experimenter expectations may
      influence participant behavior, we asked whether a short pre-experiment
      interaction between participants and experimenters would contribute to priming
      effects when experimenters were not blind to participant condition. An initial
      double-blind experiment failed to demonstrate the expected effects of a social
      prime on executive cognition. To determine whether double-blind procedures caused
      this result, we independently manipulated participants' exposure to a prime and
      experimenters' belief about which prime participants received. Across four
      experiments, we found that experimenter belief, rather than prime condition,
      altered participant behavior. Experimenter belief also altered participants'
      perceptions of their experimenter, suggesting that differences in experimenter
      behavior across conditions caused the effect. Findings reinforce double-blind
      designs as experimental best practice and suggest that people's prior beliefs
      have important consequences for shaping behavior with an interaction partner.

PMID- 29377788
TI  - Factors Influencing Transition to Shisheh (Methamphetamine) among Young People
      Who Use Drugs in Tehran: A Qualitative Study.
AB  - BACKGROUND: Iran has experienced an emerging epidemic of methamphetamine use
      during recent years which has added to existing non-injecting and injecting
      opioid use in the country. This study explored factors influencing the initiation
      into or transition to methamphetamine use among young people who use drugs
      (PWUD). METHODS: We conducted 42 semi-structured, in-depth interviews with young
      PWUD (n = 35) and health care workers (HCWs) (n = 7) between July and October
      2011 in Tehran, Iran. The PWUD were purposefully recruited from different tiers
      of drug services and lived in geographically diverse areas of Tehran. The HCWs
      were substance use experts and/or service providers of treatment and harm
      reduction facilities. All interviews were recorded, transcribed, and coded using
      OpenCode 3.6 software. RESULTS: The predominant factors for initiation into or
      transition to methamphetamine use were individual domain factors. The peer domain
      factors were the second most frequently stated perceived factor category for
      transition to methamphetamine use. Other perceived factors affecting transition
      to stimulant use included both family and community domains. CONCLUSION: Drug
      prevention programs should consider targeting certain settings, including
      workplaces and sports clubs, for preventative interventions. Existing opioid
      treatment and harm reduction services should be adjusted in response to the
      methamphetamine use epidemic.

PMID- 29377785
TI  - Communicating with Daughters About Familial Risk of Breast Cancer: Individual,
      Family, and Provider Influences on Women's Knowledge of Cancer Risk.
AB  - INTRODUCTION: Women facing complex and uncertain situations such as cancer in
      their families may seek information from a variety of sources to gain knowledge
      about cancer risk and reduce uncertainty. We describe and assess the relative
      importance of information sources about familial breast cancer at the individual,
      family, and healthcare provider levels influencing women's reporting they had
      enough information to speak with daughters about breast cancer. This outcome we
      refer to as being informed about breast cancer. MATERIALS AND METHODS: Sister
      Study participants, a cohort of women with a family history of breast cancer,
      were surveyed on family cancer history, family communication, social support, and
      interactions with healthcare providers (n = 11,766). Adjusted percentages and 95%
      confidence intervals for being informed about breast cancer versus not being
      informed were computed for individual-, family-, and provider-level
      characteristics in three steps using multivariate logistic regression models.
      RESULTS: We found 65% of women reported being informed about breast cancer while
      35% did not. Having a trusted person with whom to discuss cancer concerns, having
      a lower versus higher perceived risk of breast cancer, having undergone genetic
      counseling, and being satisfied with physician discussions about breast cancer in
      their families were predictors of being informed about breast cancer.
      CONCLUSIONS: Although acquiring objective risk information, such as through
      genetic counseling, may contribute to a basic level of understanding,
      communication with providers and within other trusted relationships appears to be
      an essential component in women's reporting they had all the information they
      need to talk with their daughters about breast cancer.

PMID- 29377790
TI  - Corrigendum.

PMID- 29377789
TI  - Influence of grass pellet production on pyrrolizidine alkaloids occurring in
      Senecio aquaticus-infested grassland.
AB  - 1,2-Dehydro-pyrrolizidine alkaloids (PA) and their N-oxides (PANO) exhibit acute
      and chronic toxic effects on the liver and other organs and therefore are a
      hazard for animal and human health. In certain regions of Germany, an increasing
      spread of Senecio spp. (ragwort) on grassland and farmland areas has been
      observed during the last years leading to a PA/PANO-contamination of feed and
      food of animal and plant origin. This project was carried out to elucidate
      whether the process of grass pellet production applying hot air drying influences
      the content of PA and PANO. Samples of hay (n = 22) and grass pellets (n = 28)
      originated from naturally infested grassland (around 10% and 30% dominance of
      Senecio aquaticus) and from a trial plot with around 50% dominance. Grass pellets
      were prepared from grass originating from exactly the same plots as the hay
      samples. The samples were analysed by liquid chromatography-tandem mass
      spectrometry for PA/PANO typically produced by this weed. The results of the
      study revealed that PA/PANO levels (predominantly sum of senecionine,
      seneciphylline, erucifoline and their N-oxides) in hay ranged between 2.1 and
      12.6 mg kg-1 dry matter in samples with 10% and 30% dominance of S. aquaticus,
      respectively. Samples from the trial plot (50% dominance) had levels of up to
      52.9 mg kg-1. Notably, the hot air drying process during the production of grass
      pellets did not lead to a reduction of PA/PANO levels. Instead, the levels in
      grass pellets with 10% and 30% S. aquaticus ranged from 3.1 to 55.1 mg kg-1.
      Grass pellets from the trial plot contained up to 96.8 mg kg-1. In conclusion,
      hot air drying and grass pellet production did not affect PA/PANO contents in
      plant material and therefore, heat-dried products cannot be regarded as safe in
      view of the toxic potential of 1,2-dehydro-pyrrolizidine alkaloids.

PMID- 29377791
TI  - The Action Level.

PMID- 29377792
TI  - Hsp70-associated chaperones have a critical role in buffering protein production
      costs.
AB  - Proteins are necessary for cellular growth. Concurrently, however, protein
      production has high energetic demands associated with transcription and
      translation. Here, we propose that activity of molecular chaperones shape protein
      burden, that is the fitness costs associated with expression of unneeded
      proteins. To test this hypothesis, we performed a genome-wide genetic interaction
      screen in baker's yeast. Impairment of transcription, translation, and protein
      folding rendered cells hypersensitive to protein burden. Specifically, deletion
      of specific regulators of the Hsp70-associated chaperone network increased
      protein burden. In agreement with expectation, temperature stress, increased
      mistranslation and a chemical misfolding agent all substantially enhanced protein
      burden. Finally, unneeded protein perturbed interactions between key components
      of the Hsp70-Hsp90 network involved in folding of native proteins. We conclude
      that specific chaperones contribute to protein burden. Our work indicates that by
      minimizing the damaging impact of gratuitous protein overproduction, chaperones
      enable tolerance to massive changes in genomic expression.

PMID- 29377795
TI  - Statistically Reconstructed Multiplexing for Very Dense, High-Channel-Count
      Acquisition Systems.
AB  - Multiplexing is an important strategy in multichannel acquisition systems. The
      per-channel antialiasing filters needed in the traditional multiplexing
      architecture limit its scalability for applications requiring high channel
      density, high channel count, and low noise. A particularly challenging example is
      multielectrode arrays for recording from neural systems. We show that
      conventional approaches must tradeoff recording density and noise performance, at
      a scale far from the ideal goal of one-to-one mapping between neurons and
      sensors. We present a multiplexing architecture without per-channel antialiasing
      filters. The sparsely sampled data are recovered through a compressed sensing
      strategy, involving statistical reconstruction and removal of the undersampled
      thermal noise. In doing so, we replace large analog components with digital
      signal processing blocks, which are much more amenable to scaled CMOS
      implementation. The resulting statistically reconstructed multiplexing
      architecture recovers input signals at significantly improved signal-to-noise
      ratios when compared to conventional multiplexing with antialiasing filters at
      the same per-channel area. We implement the new architecture in a 65 536-channel
      neural recording system and show that it is able to recover signals with
      performance comparable to conventional high-performance, single-channel systems,
      despite a more than four-orders-of-magnitude increase in channel density.

PMID- 29377793
TI  - Prediction of enzymatic pathways by integrative pathway mapping.
AB  - The functions of most proteins are yet to be determined. The function of an
      enzyme is often defined by its interacting partners, including its substrate and
      product, and its role in larger metabolic networks. Here, we describe a
      computational method that predicts the functions of orphan enzymes by organizing
      them into a linear metabolic pathway. Given candidate enzyme and metabolite
      pathway members, this aim is achieved by finding those pathways that satisfy
      structural and network restraints implied by varied input information, including
      that from virtual screening, chemoinformatics, genomic context analysis, and
      ligand -binding experiments. We demonstrate this integrative pathway mapping
      method by predicting the L-gulonate catabolic pathway in Haemophilus influenzae
      Rd KW20. The prediction was subsequently validated experimentally by enzymology,
      crystallography, and metabolomics. Integrative pathway mapping by satisfaction of
      structural and network restraints is extensible to molecular networks in general
      and thus formally bridges the gap between structural biology and systems biology.

PMID- 29377794
TI  - Hepatitis B virus core protein allosteric modulators can distort and disrupt
      intact capsids.
AB  - Defining mechanisms of direct-acting antivirals facilitates drug development and
      our understanding of virus function. Heteroaryldihydropyrimidines (HAPs)
      inappropriately activate assembly of hepatitis B virus (HBV) core protein (Cp),
      suppressing formation of virions. We examined a fluorophore-labeled HAP, HAP
      TAMRA. HAP-TAMRA induced Cp assembly and also bound pre-assembled capsids.
      Kinetic and spectroscopic studies imply that HAP-binding sites are usually not
      available but are bound cooperatively. Using cryo-EM, we observed that HAP-TAMRA
      asymmetrically deformed capsids, creating a heterogeneous array of sharp angles,
      flat regions, and outright breaks. To achieve high resolution reconstruction (<4
      A), we introduced a disulfide crosslink that rescued particle symmetry. We
      deduced that HAP-TAMRA caused quasi-sixfold vertices to become flatter and
      fivefold more angular. This transition led to asymmetric faceting. That a
      disordered crosslink could rescue symmetry implies that capsids have tensegrity
      properties. Capsid distortion and disruption is a new mechanism by which
      molecules like the HAPs can block HBV infection.

PMID- 29377796
TI  - A Low-Power Wearable Stand-Alone Tongue Drive System for People With Severe
      Disabilities.
AB  - This paper presents a low-power stand-alone tongue drive system (sTDS) used for
      individuals with severe disabilities to potentially control their environment
      such as computer, smartphone, and wheelchair using their voluntary tongue
      movements. A low-power local processor is proposed, which can perform signal
      processing to convert raw magnetic sensor signals to user-defined commands, on
      the sTDS wearable headset, rather than sending all raw data out to a PC or
      smartphone. The proposed sTDS significantly reduces the transmitter power
      consumption and subsequently increases the battery life. Assuming the sTDS user
      issues one command every 20 ms, the proposed local processor reduces the data
      volume that needs to be wirelessly transmitted by a factor of 64, from 9.6 to
      0.15 kb/s. The proposed processor consists of three main blocks: serial
      peripheral interface bus for receiving raw data from magnetic sensors, external
      magnetic interference attenuation to attenuate external magnetic field from the
      raw magnetic signal, and a machine learning classifier for command detection. A
      proof-of-concept prototype sTDS has been implemented with a low-power IGLOO-nano
      field programmable gate array (FPGA), bluetooth low energy, battery and magnetic
      sensors on a headset, and tested. At clock frequency of 20 MHz, the processor
      takes 6.6 s and consumes 27 nJ for detecting a command with a detection accuracy
      of 96.9%. To further reduce power consumption, an application-specified
      integrated circuit processor for the sTDS is implemented at the postlayout level
      in 65-nm CMOS technology with 1-V power supply, and it consumes 0.43 mW, which is
      10 lower than FPGA power consumption and occupies an area of only 0.016 mm.

PMID- 29377797
TI  - An Embedded, Eight Channel, Noise Canceling, Wireless, Wearable sEMG Data
      Acquisition System With Adaptive Muscle Contraction Detection.
AB  - Wearable technology has gained increasing popularity in the applications of
      healthcare, sports science, and biomedical engineering in recent years. Because
      of its convenient nature, the wearable technology is particularly useful in the
      acquisition of the physiological signals. Specifically, the (surface
      electromyography) sEMG systems, which measure the muscle activation potentials,
      greatly benefit from this technology in both clinical and industrial
      applications. However, the current wearable sEMG systems have several drawbacks
      including inefficient noise cancellation, insufficient measurement quality, and
      difficult integration to customized applications. Additionally, none of these
      sEMG data acquisition systems can detect sEMG signals (i.e., contractions), which
      provides a valuable environment for further studies such as human machine
      interaction, gesture recognition, and fatigue tracking. To this end, we introduce
      an embedded, eight channel, noise canceling, wireless, wearable sEMG data
      acquisition system with adaptive muscle contraction detection. Our design
      consists of two stages, which are the sEMG sensors and the multichannel data
      acquisition unit. For the first stage, we propose a low cost, dry, and active
      sEMG sensor that captures the muscle activation potentials, a data acquisition
      unit that evaluates these captured multichannel sEMG signals and transmits them
      to a user interface. In the data acquisition unit, the sEMG signals are processed
      through embedded, adaptive methods in order to reject the power line noise and
      detect the muscle contractions. Through extensive experiments, we demonstrate
      that our sEMG sensor outperforms a widely used commercially available product and
      our data acquisition system achieves 4.583 dB SNR gain with accuracy in the
      detection of the contractions.

PMID- 29377798
TI  - 1024-Pixel CMOS Multimodality Joint Cellular Sensor/Stimulator Array for Real
      Time Holistic Cellular Characterization and Cell-Based Drug Screening.
AB  - This paper presents a fully integrated CMOS multimodality joint sensor/stimulator
      array with 1024 pixels for real-time holistic cellular characterization and drug
      screening. The proposed system consists of four pixel groups and four parallel
      signal-conditioning blocks. Every pixel group contains 16 * 16 pixels, and each
      pixel includes one gold-plated electrode, four photodiodes, and in-pixel
      circuits, within a pixel footprint. Each pixel supports real-time extracellular
      potential recording, optical detection, charge-balanced biphasic current
      stimulation, and cellular impedance measurement for the same cellular sample. The
      proposed system is fabricated in a standard 130-nm CMOS process. Rat
      cardiomyocytes are successfully cultured on-chip. Measured high-resolution
      optical opacity images, extracellular potential recordings, biphasic current
      stimulations, and cellular impedance images demonstrate the unique advantages of
      the system for holistic cell characterization and drug screening. Furthermore,
      this paper demonstrates the use of optical detection on the on-chip cultured
      cardiomyocytes to real-time track their cyclic beating pattern and beating rate.

PMID- 29377799
TI  - In Vivo Characterization of a Wireless Telemetry Module for a Capsule Endoscopy
      System Utilizing a Conformal Antenna.
AB  - This paper describes the design, fabrication, packaging, and performance
      characterization of a conformal helix antenna created on the outside of a capsule
      endoscope designed to operate at a carrier frequency of 433 MHz within human
      tissue. Wireless data transfer was established between the integrated capsule
      system and an external receiver. The telemetry system was tested within a tissue
      phantom and in vivo porcine models. Two different types of transmission modes
      were tested. The first mode, replicating normal operating conditions, used data
      packets at a steady power level of 0 dBm, while the capsule was being withdrawn
      at a steady rate from the small intestine. The second mode, replicating the worst
      case clinical scenario of capsule retention within the small bowel, sent data
      with stepwise increasing power levels of -10, 0, 6, and 10 dBm, with the capsule
      fixed in position. The temperature of the tissue surrounding the external antenna
      was monitored at all times using thermistors embedded within the capsule shell to
      observe potential safety issues. The recorded data showed, for both modes of
      operation, a low error transmission of 10-3 packet error rate and 10-5 bit error
      rate and no temperature increase of the tissue according to IEEE standards.

PMID- 29377800
TI  - A Scalable Multicore Architecture With Heterogeneous Memory Structures for
      Dynamic Neuromorphic Asynchronous Processors (DYNAPs).
AB  - Neuromorphic computing systems comprise networks of neurons that use asynchronous
      events for both computation and communication. This type of representation offers
      several advantages in terms of bandwidth and power consumption in neuromorphic
      electronic systems. However, managing the traffic of asynchronous events in large
      scale systems is a daunting task, both in terms of circuit complexity and memory
      requirements. Here, we present a novel routing methodology that employs both
      hierarchical and mesh routing strategies and combines heterogeneous memory
      structures for minimizing both memory requirements and latency, while maximizing
      programming flexibility to support a wide range of event-based neural network
      architectures, through parameter configuration. We validated the proposed scheme
      in a prototype multicore neuromorphic processor chip that employs hybrid
      analog/digital circuits for emulating synapse and neuron dynamics together with
      asynchronous digital circuits for managing the address-event traffic. We present
      a theoretical analysis of the proposed connectivity scheme, describe the methods
      and circuits used to implement such scheme, and characterize the prototype chip.
      Finally, we demonstrate the use of the neuromorphic processor with a
      convolutional neural network for the real-time classification of visual symbols
      being flashed to a dynamic vision sensor (DVS) at high speed.

PMID- 29377801
TI  - A Sensitive Dynamic and Active Pixel Vision Sensor for Color or Neural Imaging
      Applications.
AB  - Applications requiring detection of small visual contrast require high
      sensitivity. Event cameras can provide higher dynamic range (DR) and reduce data
      rate and latency, but most existing event cameras have limited sensitivity. This
      paper presents the results of a 180-nm Towerjazz CIS process vision sensor called
      SDAVIS192. It outputs temporal contrast dynamic vision sensor (DVS) events and
      conventional active pixel sensor frames. The SDAVIS192 improves on previous DAVIS
      sensors with higher sensitivity for temporal contrast. The temporal contrast
      thresholds can be set down to 1% for negative changes in logarithmic intensity
      (OFF events) and down to 3.5% for positive changes (ON events). The achievement
      is possible through the adoption of an in-pixel preamplification stage. This
      preamplifier reduces the effective intrascene DR of the sensor (70 dB for OFF and
      50 dB for ON), but an automated operating region control allows up to at least
      110-dB DR for OFF events. A second contribution of this paper is the development
      of characterization methodology for measuring DVS event detection thresholds by
      incorporating a measure of signal-to-noise ratio (SNR). At average SNR of 30 dB,
      the DVS temporal contrast threshold fixed pattern noise is measured to be 0.3%
      0.8% temporal contrast. Results comparing monochrome and RGBW color filter array
      DVS events are presented. The higher sensitivity of SDAVIS192 make this sensor
      potentially useful for calcium imaging, as shown in a recording from cultured
      neurons expressing calcium sensitive green fluorescent protein GCaMP6f.

PMID- 29377802
TI  - SVD and ASCII Character Encoding-Based Compression of Multiple Biosignals for
      Remote Healthcare Systems.
AB  - Advancements in electronics and miniaturized device fabrication technologies have
      enabled simultaneous acquisition of multiple biosignals (MBioSigs), but the area
      of compression of MBioSigs remains unexplored to date. This paper presents a
      robust singular value decomposition (SVD) and American standard code for
      information interchange (ASCII) character encoding-based algorithm for
      compression of MBioSigs for the first time to the best of our knowledge. At the
      preprocessing stage, MBioSigs are denoised, down sampled and then transformed to
      a two-dimensional (2-D) data array. SVD of the 2-D array is carried out and the
      dimensionality of the singular values is reduced. The resulting matrix is then
      compressed by a lossless ASCII character encoding-based technique. The proposed
      compression algorithm can be used in a variety of modes such as lossless, with or
      without using the down sampling operation. The compressed file is then uploaded
      to a hypertext preprocessor (PHP)-based website for remote monitoring
      application. Evaluation results show that the proposed algorithm provides a good
      compression performance; in particular, the mean opinion score of the
      reconstructed signal falls under the category "very good" as per the gold
      standard subjective measure.

PMID- 29377803
TI  - PERSON-Personalized Expert Recommendation System for Optimized Nutrition.
AB  - The rise of personalized diets is due to the emergence of nutrigenetics and
      genetic tests services. However, the recommendation system is far from mature to
      provide personalized food suggestion to consumers for daily usage. The main
      barrier of connecting genetic information to personalized diets is the complexity
      of data and the scalability of the applied systems. Aiming to cross such barriers
      and provide direct applications, a personalized expert recommendation system for
      optimized nutrition is introduced in this paper, which performs direct to
      consumer personalized grocery product filtering and recommendation. Deep learning
      neural network model is applied to achieve automatic product categorization. The
      ability of scaling with unknown new data is achieved through the generalized
      representation of word embedding. Furthermore, the categorized products are
      filtered with a model based on individual genetic data with associated phenotypic
      information and a case study with databases from three different sources is
      carried out to confirm the system.

PMID- 29377804
TI  - An On-Chip Learning Neuromorphic Autoencoder With Current-Mode Transposable
      Memory Read and Virtual Lookup Table.
AB  - This paper presents an IC implementation of on-chip learning neuromorphic
      autoencoder unit in a form of rate-based spiking neural network. With a current
      mode signaling scheme embedded in a 500 * 500 6b SRAM-based memory, the proposed
      architecture achieves simultaneous processing of multiplications and
      accumulations. In addition, a transposable memory read for both forward and
      backward propagations and a virtual lookup table are also proposed to perform an
      unsupervised learning of restricted Boltzmann machine. The IC is fabricated using
      28-nm CMOS process and is verified in a three-layer network of encoder-decoder
      pair for training and recovery of images with two-dimensional pixels. With a
      dataset of 50 digits, the IC shows a normalized root mean square error of 0.078.
      Measured energy efficiencies are 4.46 pJ per synaptic operation for inference and
      19.26 pJ per synaptic weight update for learning, respectively. The learning
      performance is also estimated by simulations if the proposed hardware
      architecture is extended to apply to a batch training of 60 000 MNIST datasets.

PMID- 29377805
TI  - VLSI Design of SVM-Based Seizure Detection System With On-Chip Learning
      Capability.
AB  - Portable automatic seizure detection system is very convenient for epilepsy
      patients to carry. In order to make the system on-chip trainable with high
      efficiency and attain high detection accuracy, this paper presents a very large
      scale integration (VLSI) design based on the nonlinear support vector machine
      (SVM). The proposed design mainly consists of a feature extraction (FE) module
      and an SVM module. The FE module performs the three-level Daubechies discrete
      wavelet transform to fit the physiological bands of the electroencephalogram
      (EEG) signal and extracts the time-frequency domain features reflecting the
      nonstationary signal properties. The SVM module integrates the modified
      sequential minimal optimization algorithm with the table-driven-based Gaussian
      kernel to enable efficient on-chip learning. The presented design is verified on
      an Altera Cyclone II field-programmable gate array and tested using the two
      publicly available EEG datasets. Experiment results show that the designed VLSI
      system improves the detection accuracy and training efficiency.

PMID- 29377806
TI  - Sensing Passive Eye Response to Impact Induced Head Acceleration Using MEMS IMUs.
AB  - The eye may act as a surrogate for the brain in response to head acceleration
      during an impact. Passive eye movements in a dynamic system are sensed by
      microelectromechanical systems (MEMS) inertial measurement units (IMU) in this
      paper. The technique is validated using a three-dimensional printed scaled human
      skull model and on human volunteers by performing drop-and-impact experiments
      with ribbon-style flexible printed circuit board IMUs inserted in the eyes and
      reference IMUs on the heads. Data are captured by a microcontroller unit and
      processed using data fusion. Displacements are thus estimated and match the
      measured parameters. Relative accelerations and displacements of the eye to the
      head are computed indicating the influence of the concussion causing impacts.

PMID- 29377807
TI  - Simultaneous Multimodal PC Access for People With Disabilities by Integrating
      Head Tracking, Speech Recognition, and Tongue Motion.
AB  - Multimodal Tongue Drive System (mTDS) is a highly integrated wireless assistive
      technology (AT) in the form of a lightweight wearable headset that utilizes three
      remaining key control and communication abilities in people with severe physical
      disabilities, such as tetraplegia, to provide them with effective access to
      computers: 1) tongue motion for discrete/switch-based control (e.g., clicking),
      2) head tracking for proportional control (e.g., mouse pointer movements), and 3)
      speech recognition for typing, all available simultaneously. The mTDS
      architecture is presented here with new sensor signal processing algorithm for
      head tracking. To evaluate the device performance, it was compared against
      keyboard-and-mouse (KnM) combination, the gold standard in computer input
      methods, by 15 able-bodied participants, who used both mTDS and KnM to generate
      and sent an email with randomly selected content, under a 5-minute time
      constraint. In four repetitions, in the last trial, it took participants only 1.8
      times longer to complete the email task, on average, using the mTDS versus KnM at
      82.4% typing accuracy. Mean task completion time and typing accuracy improved
      24.6% and 18.8% from first to fourth trial using mTDS. Multimodal simultaneous
      discrete and proportional control input options of mTDS, plus rapid typing, is
      expected to provide more effective computer access to people with severe physical
      disabilities.

PMID- 29377808
TI  - Cryogenic Preamplifiers for Magnetic Resonance Imaging.
AB  - Pursuing the ultimate limit of detection in magnetic resonance imaging (MRI)
      requires cryogenics to decrease the thermal noise of the electronic circuits. As
      cryogenic coils for MRI are slowly emerging cryogenic preamplifiers are required
      to fully exploit their potential. A cryogenic preamplifier operated at 77 K is
      designed and implemented for C imaging at 3 T (32.13 MHz), using off-the-shelves
      components. The design is based on a high electron mobility transistor (ATF54143)
      in a common source configuration. Required auxiliary circuitry for optimal
      cryogenic preamplifier performance is also presented consisting of a voltage
      regulator (noise free supply voltage and optimal power consumption), switch, and
      trigger (for active detuning during transmission to protect the preamplifier). A
      gain of 18 dB with a noise temperature of 13.7 K is achieved. Performing imaging
      experiments in a 3 T scanner showed an 8% increased signal-to-noise ratio from
      365 to 399 when lowering the temperature of the preamplifier from 296 to 77 K
      while keeping the coil at room temperature. This paper thus enables the merger of
      cryogenic coils and preamplifiers in the hopes of reaching the ultimate limit of
      detection for MRI.

PMID- 29377809
TI  - A 1.55 MUW Bio-Impedance Measurement System for Implantable Cardiac Pacemakers in
      0.18 MUm CMOS.
AB  - This paper presents an implantable bio-impedance measurement system for cardiac
      pacemakers. The fully integrated system features a low power analog front-end and
      pulse width modulated output. The bio-impedance readout benefits from voltage to
      time conversion to achieve a very low power consumption for wirelessly
      transmitting the data outside the body. The proposed IC is fabricated in a 0.18
      MUm CMOS process and is capable of measuring the bio-impedance at 2 kHz over a
      wide dynamic range from to with accuracy and maximum current injection while
      consuming just from a 1 V supply.

PMID- 29377810
TI  - A 10 MHz Read-Out Chain for Electrical Impedance Tomography.
AB  - This paper presents the design and implementation of a read-out chain for
      electrical impedance tomography (EIT) imaging. The EIT imaging approach can be
      incorporated to take spectral images of the tissue under study, offering an
      affordable, portable device for home health monitoring. A fast read-out channel
      covering a wide range of frequencies is a must for such applications. The
      proposed read-out channel comprising a programmable gain instrumentation
      amplifier, an analog-to-digital converter (ADC), and an ADC driver is designed
      and fabricated in a 0.18  m CMOS technology. The proposed read-out chain operates
      over the wide frequency range of 100 Hz to 10 MHz, with an average signal-to
      noise ratio of more than 60 dB. The entire read-out channel consumes between 6.9
      and 21.8 mW, depending on its frequency of operation.

PMID- 29377811
TI  - Wireless EEG System Achieving High Throughput and Reduced Energy Consumption
      Through Lossless and Near-Lossless Compression.
AB  - This work presents a wireless multichannel electroencephalogram (EEG) recording
      system featuring lossless and near-lossless compression of the digitized EEG
      signal. Two novel, low-complexity, efficient compression algorithms were
      developed and tested in a low-power platform. The algorithms were tested on six
      public EEG databases comparing favorably with the best compression rates reported
      up to date in the literature. In its lossless mode, the platform is capable of
      encoding and transmitting 59-channel EEG signals, sampled at 500 Hz and 16 bits
      per sample, at a current consumption of 337 A per channel; this comes with a
      guarantee that the decompressed signal is identical to the sampled one. The near
      lossless mode allows for significant energy savings and/or higher throughputs in
      exchange for a small guaranteed maximum per-sample distortion in the recovered
      signal. Finally, we address the tradeoff between computation cost and
      transmission savings by evaluating three alternatives: sending raw data, or
      encoding with one of two compression algorithms that differ in complexity and
      compression performance. We observe that the higher the throughput (number of
      channels and sampling rate) the larger the benefits obtained from compression.

PMID- 29377812
TI  - On-Chip Neural Data Compression Based On Compressed Sensing With Sparse Sensing
      Matrices.
AB  - On-chip neural data compression is an enabling technique for wireless neural
      interfaces that suffer from insufficient bandwidth and power budgets to transmit
      the raw data. The data compression algorithm and its implementation should be
      power and area efficient and functionally reliable over different datasets.
      Compressed sensing is an emerging technique that has been applied to compress
      various neurophysiological data. However, the state-of-the-art compressed sensing
      (CS) encoders leverage random but dense binary measurement matrices, which incur
      substantial implementation costs on both power and area that could offset the
      benefits from the reduced wireless data rate. In this paper, we propose two CS
      encoder designs based on sparse measurement matrices that could lead to efficient
      hardware implementation. Specifically, two different approaches for the
      construction of sparse measurement matrices, i.e., the deterministic quasi-cyclic
      array code (QCAC) matrix and -sparse random binary matrix [-SRBM] are exploited.
      We demonstrate that the proposed CS encoders lead to comparable recovery
      performance. And efficient VLSI architecture designs are proposed for QCAC-CS and
      -SRBM encoders with reduced area and total power consumption.

PMID- 29377813
TI  - Septage unit treatment by sludge treatment reed beds for easy management and
      reuse: performance and design considerations.
AB  - Sustainable treatment and management of fecal sludge in rural areas require
      adapted solutions. Rustic and simple operating processes such as sludge treatment
      reed beds (STRB) have been increasingly considered for this purpose. The biggest
      full scale (2,600 m2 of STRB) septage treatment unit in France had been built in
      Negrepelisse with the final objectives of reusing treated sludge and leachates
      for agriculture spreading and tree irrigation, respectively. The aim of this
      investigation was to validate the treatment chain of this installation. The
      obtained field data showed firstly that the overall removal efficiencies of STRB
      were satisfactory and stable. Removal rates higher than 98% for chemical oxygen
      demand and suspended solids and a 95% for Kjeldahl nitrogen represented so far a
      beneficial septage treatment by STRB. The highlighted necessity of a suitable
      complementary leachate treatment (before tree irrigation) justified the presence
      of the second stage of vertical flow constructed wetland. The sludge deposit
      drying and mineralization efficiencies were on the right track. According to
      hydrotextural diagram analysis, surface deposit was however found to have high
      deformability probably due to the youth of the installation. An in-depth
      understanding of STRB system needs continuous long-term studies.

PMID- 29377814
TI  - High-resolution characterization of labile phosphorus, iron, and manganese in
      sediments of different trophic waters in Lake Taihu, China.
AB  - High-resolution combined ZrO-Chelex diffusive gradients in thin film (DGT) probes
      were arranged to synchronously monitor the characteristics of labile phosphorus
      (P), iron (Fe), and manganese (Mn) in sediments from regions of varying trophic
      levels in Lake Taihu, China. Results showed that P release was closely related to
      the lake region's trophic level. Labile P in sediments and the apparent diffusion
      flux (Fd) of P were higher in hyper-eutrophic algae-dominated regions than those
      in macrophyte-algae-dominated and macrophyte-dominated regions, indicating that P
      released from sediments may be facilitated in eutrophic environments. A positive
      correlation observed between DGT-labile P and Fe or Mn, which had similar
      regional spatial distributions to P, showed that reductive dissolution of Fe-Mn
      (oxyhydr)oxides (FeOOH-MnOOH) in sediments was responsible for internal P
      release, which was strengthened in eutrophic environments. Ratios of labile Fe or
      Mn/labile P (LFe/LP and LMn/LP) in sediments in algae-dominated regions showed
      lower values than those in macrophyte-algae-dominated and macrophyte-dominated
      regions, further confirming that FeOOH-MnOOH in algae-dominated regions were less
      able to fix P, which brought higher pollution risks for the overlying water.
      LFe/LP or LMn/LP also had a significantly positive correlation with Fd, further
      testament that labile Fe or Mn was much more relevant to the sediment P cycle.

PMID- 29377815
TI  - Effect of a static magnetic field on the microscopic characteristics of highly
      efficient oil-removing bacteria.
AB  - To better understand the microbial oil removal enhancement process by a magnetic
      field, the effect of a static magnetic field (SMF) on the microscopic
      characteristics of highly efficient biodegradation oil-removing bacteria was
      studied. The Acinetobacter sp. B11 strain with a 53.6% oil removal rate was
      selected as the reference bacteria. The changes in the microscopic
      characteristics of Acinetobacter sp. B11 such as the cell surface morphology,
      cell permeability and cell activity of the bacteria were investigated. The
      results showed that low-intensity magnetic fields (15-35 mT) improved the ability
      of Acinetobacter sp. B11 to remove oil by 11.9% at 25 mT compared with that of
      bacteria with no magnetic field. Without destroying the cell membrane, the low
      intensity magnetic fields increased the cell membrane permeability and improved
      the activity of superoxide dismutase (SOD), which effectively enhanced the oil
      degradation performance of the bacteria.

PMID- 29377816
TI  - Reuse and recovery of raw hospital wastewater containing ofloxacin after
      photocatalytic treatment with nano graphene oxide magnetite.
AB  - Inadequate treatment of hospital wastewater could result in considerable risks to
      public health due to its macro- and micropollutant content. In order to eliminate
      this problem, a new nanoparticle composite was produced under laboratory
      conditions and a photocatalytic degradation approach was used. Chemical oxygen
      demand (COD), biological oxygen demand (BOD5), total suspended solids (TSS),
      total Kjeldahl nitrogen (TKN), total phosphorus (TP) (macro) and oflaxin (micro)
      pollutant removal were investigated with the nano graphene oxide magnetite (Nano
      GO/M) particles by two different processes, namely adsorption and
      photodegradation. Low removal efficiencies (21-60%) were obtained in the
      adsorption process for the parameters given above, after 90 min contact time at a
      pH of 7.8 with 5 g/L Nano-GO/M composite. Using the photodegradation process,
      higher removal efficiencies were obtained with 2 g/L Nano-GO/M composite for COD
      (88%), TSS (82%), TKN (95%) and oflaxin (97%), at pH 7.8 after 60 min irradiation
      time at a UV power of 300 W. The synthesized nanoparticle was reused for two
      sequential treatments of pharmaceutical wastewater with no significant losses of
      removal efficiencies (for oflaxin 97%-90%). The quality of the treated hospital
      wastewater was first class according to the Turkish Water Pollution Control
      Regulations criteria. This water could also be used for irrigation purposes.

PMID- 29377817
TI  - Modeling adsorption kinetic of crystal violet removal by electrocoagulation
      technique using bipolar iron electrodes.
AB  - This paper studies the removal of crystal violet (CV) dye by electrocoagulation
      (EC) process using bipolar iron electrodes. Numerous operating parameters such as
      initial CV solution concentration, speed of agitation, number of electrodes, type
      and quantity of supporting electrolyte, temperature- and initial pH were
      investigated. A complete removal of 10 mg/L CV was achieved within 10 min at pH
      7, 0.5 g NaCl, 1 LCV, 750 rpm, 9 sheets, 17.36 mAcm2, and 25  degrees C. The
      performed energy-dispersive X-ray spectroscopy (EDAX), scanning electron
      microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) analyses
      confirmed the adsorption of CV onto the insoluble iron hydroxide flocs. Amongst
      the studied adsorption isotherms models, Langmuir and Dubinin-Radushkevich were
      the most applicable. The kinetic of adsorption of CV onto flocs during the EC
      operation was studied using the pseudo-first-order, pseudo-second-order, and
      intraparticulate diffusion models, with results affirming that the adsorption
      process proceeded according to the pseudo-second-order model. The study of
      thermodynamic parameters (DeltaG0, DeltaH0, and DeltaS0,) of the CV removal at
      different temperatures reflected the feasibility of the spontaneous randomness of
      endothermic adsorption, especially at lower temperatures. The multiple regression
      equation of the removal of CV by EC technique under the different studied
      conditions was predicted.

PMID- 29377818
TI  - Status quo report on wastewater treatment plant, receiving water's biocoenosis
      and quality as basis for evaluation of large-scale ozonation process.
AB  - The project DemO3AC (demonstration of large-scale wastewater ozonation at the
      Aachen-Soers wastewater treatment plant, Germany) of the Eifel-Rur Waterboard
      contains the construction of a large-scale ozonation plant for advanced treatment
      of the entire 25 million m3/yr of wastewater passing through its largest
      wastewater treatment plant (WWTP). In dry periods, up to 70% of the receiving
      water consists of treated wastewater. Thus, it is expected that effects of
      ozonation on downstream water biocoenosis will become observable. Extensive
      monitoring of receiving water and the WWTP shows a severe pollution with
      micropollutants (already prior to WWTP inlet). (Eco-)Toxicological investigations
      showed increased toxicity at the inlet of the WWTP for all assays. However,
      endocrine-disrupting potential was also present at other sampling points at the
      WWTP and in the river and could not be eliminated sufficiently by the WWTP. Total
      cell counts at the WWTP are slightly below average. Investigations of antibiotic
      resistances show no increase after the WWTP outlet in the river. However, cells
      carrying antibiotic-resistant genes seem to be more stress resistant in general.
      Comparing investigations after implementation of ozonation should lead to an
      approximation of the correlation between micropollutants and water
      quality/biocoenosis and the effects that ozonation has on this matter.

PMID- 29377819
TI  - Preparation and characterization of polysulfone/zeolite mixed matrix membranes
      for removal of low-concentration ammonia from aquaculture wastewater.
AB  - Removal of low-concentration ammonia (1-10 ppm) from aquaculture wastewater was
      investigated via polysulfone (PSf)/zeolite mixed matrix membrane. PSf/zeolite
      mixed matrix membranes with different weight ratios (90/10, 80/20, 70/30 and
      60/40 wt.%) were prepared and characterized. Results indicate that PSf/zeolite
      (80/20) was the most efficient membrane for removal of low-concentration ammonia.
      The ammonia elimination by PSf/zeolite (80/20) from aqueous solution for 10, 7,
      5, 3 and 1 ppm of ammonia was 100%, 99%, 98.8%, 96% and 95% respectively. The
      recorded results revealed that pure water flux declined in higher loading of
      zeolite in the membrane matrix due to surface pore blockage caused by zeolite
      particles. On the other hand, ammonia elimination from water was decreased in
      higher contents of zeolite because of formation of cavities and macrovoids in the
      membrane substructure.

PMID- 29377820
TI  - Volumetric modeling of two sludge piles from water treatment plants in a
      Brazilian reservoir.
AB  - Water treatment plants are designed to continuously produce drinkable water,
      meeting defined criteria of potability. However, besides potable water, these
      plants produce sludges that are disposed of in the environment. The present work
      aimed to evaluate the sludges generated in two water treatment plants and
      disposed of in the margin of the Juturnaiba dam. Since alum has been used as a
      flocculating agent in these two plants, the concentrations of aluminum were
      measured in the sludges and in surface sediments. The generated piles are
      extremely soft to walk on and difficult to measure, so indirect modeling
      procedures had to be applied. The calculated mass of the sludge piles at each
      plant are similar and respectively 60,370 and 61,479 tons. The aluminum content
      of the residues, calculated according to its dosage, was 33.2 and 32.6 g kg-1 in
      the piles from the two plants. The amount of alum dosed to the water corresponds
      almost to the excess of aluminum in the sludge, compared to the sediments. It was
      concluded that regardless of the fact that residues are disposed of in very
      restricted areas, they are directly in contact with the water and may constitute
      a threat for the environment and humans' health.

PMID- 29377821
TI  - Gasification of yeast industry treatment plant sludge using downdraft Gasifier.
AB  - Sludges produced in biological wastewater treatment plants have rich organic
      materials in their characteristics. Recent research studies have focused on the
      energy recovery from sludge due to its high organic content. The gasification
      process is a thermal conversion technology transforming the chemical energy
      contained in a solid fuel into thermal energy and electricity. The produced
      syngas as a mixture of CO, CH4, H2 and other gases can be used to generate
      electrical energy. The gasification of yeast industry sludge has been
      experimentally evaluated in a pilot scale downdraft-type gasifier as a route
      towards the energy recovery. The gasifier has 20 kg biomass/h fuel capacity.
      During gasification, the temperature achieved was more than 1,000 degrees C in
      the gasifier, and then the syngas was transferred to the gas engine to yield the
      electricity. A load was connected to the grid box and approximately 1 kWh
      electrical power generation for 1 kg dry sludge was determined. The
      characteristics of residuals - ash, glassy material - were also analyzed. It was
      found that most of the heavy metals were fixed in the glassy material.
      Experimental results showed that the yeast industry sludge was an appropriate
      material for gasification studies and remarkable energy recovery was obtained in
      terms of power production by using syngas.

PMID- 29377822
TI  - Remediation of arsenic(III) from aqueous solutions using zero-valent iron (ZVI)
      combined with potassium permanganate and ferrous ions.
AB  - A system of zerovalent iron combined with potassium permanganate and ferrous
      irons (Fe(II)-KMnO4-ZVI) was used to remove As(III), one of the most poisonous
      wastewater pollutants. The Fe(II)-KMnO4-ZVI system was characterized by using X
      ray photoelectron spectroscopy and scanning electron microscopy. The As(III)
      removal efficiency by the Fe(II)-KMnO4-ZVI system under different conditions was
      investigated and the experimental data were fitted to adsorption kinetics and
      isotherm models. As(III) could be removed by both physisorption and chemisorption
      through mixing adsorbents in a very short time (minute scale) with high removal
      ratios (more than 99.5%) over a wide range of pH (1-9) and concentration (20-100
      mg/L). The removal of As(III) by the Fe(II)-KMnO4-ZVI system agreed well with
      pseudo-first-order reaction kinetics and pseudo-second-order reaction kinetics.
      The Freundlich isotherm provided a good model of the adsorption system,
      indicating that the Fe(II)-KMnO4-ZVI system has heterogeneous structure. The
      results show that the Fe(II)-KMnO4-ZVI system exhibited a high removal efficiency
      for As(III), which suggested that it might be an effective material for As(III)
      remediation.

PMID- 29377823
TI  - Evaluation of microbial fuel cell (MFC) for bioelectricity generation and
      pollutants removal from sugar beet processing wastewater (SBPW).
AB  - Bioelectricity generation from biodegradable compounds using microbial fuel cells
      (MFCs) offers an opportunity for simultaneous wastewater treatment. This study
      evaluated the synergy of electricity generation by the MFC while reducing
      pollutants from sugar beet processing wastewater (SBPW). A simple dual-chamber
      MFC was constructed with inexpensive materials without using catalysts. Raw SBPW
      was diluted to several concentrations (chemical oxygen demand (COD) of 505 to
      5,750 mg L-1) and fed as batch-mode into the MFC without further modification. A
      power density of 14.9 mW m-2 as power output was observed at a COD concentration
      of 2,565 mg L-1. Coulombic efficiency varied from 6.21% to 0.73%, indicating
      diffusion of oxygen through the cation exchange membrane and other methanogenesis
      and fermentation processes occurring in the anode chamber. In this study, >97% of
      the COD and up to 100% of the total suspended solids removals were observed from
      MFC-treated SBPW. Scanning electron microscopy of anode indicated that a diverse
      community of microbial consortia was active for electricity generation and
      wastewater treatment. This study demonstrated that SBPW can be used as a
      substrate in the MFC to generate electricity as well as to treat for pollutant
      removal.

PMID- 29377824
TI  - Recycling food waste to clean water: the use of a biodigester's residual liquid
      inoculum (RLI) to decolourise textile azo dyes.
AB  - A residual liquid inoculum (RLI) was used to decolourise solutions of Acid Yellow
      25 (AY25) and Direct Violet 51 (DV51) azo dyes. The RLI was obtained through
      anaerobic digestion of food waste from a university restaurant. The concentration
      of bacteria in the RLI was 8.45 * 107 CFU mL-1. Dye solutions (50 MUg mL-1) were
      inoculated with the RLI (20% v/v) and incubated at room temperature. The
      decolourisation studies took place at microaerophilic and in-batch conditions and
      at pH = 2.50. Initially, the dyes were taken up from solution by biosorption;
      maximum colour removal was achieved after 3 hours of incubation, with 88.66% for
      AY25 and 77.65% of DV51. At prolonged incubation times (3-96 hours)
      decolourisation was mainly attributed to biodegradation of the azo solutions,
      with breakage of the azo bond, as detected by UV-VIS spectroscopy and Fourier
      transform infrared (FT-IR) analysis. Analysis of UV-VIS absorption rates of dyes
      showed, however, that AY25 was more readily biodegradable whereas DV51 was more
      recalcitrant to the action of the RLI.

PMID- 29377825
TI  - Titania nano-coated quartz wool for the photocatalytic mineralisation of emerging
      organic contaminants.
AB  - Many emerging contaminants pass through conventional wastewater treatment plants,
      contaminating surface and drinking water. The implementation of advanced
      oxidation processes in existing plants for emerging contaminant remediation is
      one of the challenges for the enhancement of water quality in the industrialised
      countries. This paper reports on the production of a TiO2 nano-layer on quartz
      wool in a relevant amount, its characterisation by X-ray diffraction and scanning
      electron microscopy, and its use as a photocatalyst under ultraviolet radiation
      for the simultaneous mineralisation of five emerging organic contaminants
      (benzophenone-3, benzophenone-4, carbamazepine, diclofenac, and triton X-100)
      dissolved in deionised water and tap water. This treatment was compared with
      direct ultraviolet photolysis and with photocatalytic degradation on commercial
      TiO2 micropearls. The disappearance of every pollutant was measured by high
      performance liquid chromatography and mineralisation was assessed by the
      determination of total organic carbon. After 4 hours of treatment with the TiO2
      nano-coated quartz wool, the mineralisation exceeds 90% in deionised water and is
      about 70% in tap water. This catalyst was reused for seven cycles without
      significant efficiency loss.

PMID- 29377826
TI  - Primary productivity and climate change in Austrian lowland rivers.
AB  - There is increasing evidence of water temperature being a key controlling factor
      of stream ecosystem metabolism. Although the focus of research currently lies on
      carbon emissions from fluvial networks and their potential role as positive
      climate feedback, it is also important to estimate the risk of eutrophication
      streams will be exposed to in the future. In this work, a methodological approach
      is developed to create a scientific basis for such assessment and is applied to
      two Austrian lowland rivers with significantly different characteristics. Gross
      primary productivity (GPP) is determined through the open diel oxygen method and
      its temperature dependence is quantified based on the metabolic theory of
      ecology. This relationship is combined with the outcomes of a climate change
      scenario obtained through a novel integrated modelling framework. Results
      indicate that in both rivers, a 1.5 degrees C warming would provoke an increase
      of GPP of 7-9% and that such an increase would not be limited by nutrient
      availability. The results further suggest that the situation for the relatively
      shallow river might be more critical, given that its GPP values in summer are
      five times higher than in the deeper murky river.

PMID- 29377827
TI  - Correlation between nitrous oxide (N2O) emission and carbon to nitrogen (COD/N)
      ratio in denitrification process: a mitigation strategy to decrease greenhouse
      gas emission and cost of operation.
AB  - The reliability and accuracy of in-situ ion selective electrode and ultraviolet
      (NOx) probes have been investigated at four different treatment plants with
      different operational conditions. This study shows that the mentioned probes tend
      to compromise their accuracy and trending stability at lower NOx of <1.0 mg N/L,
      which if used as a measuring variable for PI feedback controller for
      denitrification (biological reduction of nitrate to nitrogen gas), would cause
      overfeeding the external carbon source. In-situ Clark-type N2O sensors, recently
      introduced for industrial scale use (Unisense Environment) could potentially open
      a new horizon in the automation of biological processes and particularly
      denitrification. To demonstrate the applicability of such probes for automation,
      two in-situ N2O probes were used in two treatment plants in parallel with NOx-N
      probes. The effects of operational conditions such as COD/N ratios and the
      correlation between NOx and N2O were investigated at those plants. N2O production
      at non-detect dissolved oxygen concentrations and pH of 7-7.2 were found to be a
      function of influent nitrogen load or the ratio of COD/NINFLUENT. Finally, using
      an N2O probe as a proxy sensor for nitrates is proposed as a measured variable in
      the PI feedback in the automation of the denitrification process with a NOx set
      point of <1.2 mg N/L).

PMID- 29377828
TI  - The role of organic matter and clay content in sediments for bioavailability of
      pyrene.
AB  - Evaluation of the bioavailable fractions of organic contaminants such as
      polycyclic aromatic hydrocarbons (PAHs) is extremely important for assessing
      their risk to the environment. This available fraction, which can be solubilised
      and/or easily extracted, is believed to be the most accessible for
      bioaccumulation, biosorption and/or transformation. Sediment organic matter (OM)
      and clay play an important role in the biodegradation and bioavailability of
      PAHs. The strong association of PAHs with OM and clay in sediments has a great
      influence not only on their distribution but also on their long-term
      environmental impact. This paper investigates correlations between
      bioavailability and the clay and OM contents in sediments. The results show that
      OM is a better sorbent for pyrene (chosen as a model PAH) and that increasing the
      OM content reduces the bioavailable fraction. A mathematical model was used to
      predict the kinetic desorption, and these results showed that the sediment with
      the lowest content of OM had an Ffast value of 24%, whereas sediment with 20% OM
      gave a value of 9%. In the experiments with sediments with different clay
      contents, no clear dependence between clay and rate constants of the fast
      desorbing fractions was observed, which can be explained by the numerous possible
      interactions at the molecular level.

PMID- 29377830
TI  - Recovery of phenolic compounds from multi-component solution by a synthesized
      activated carbon using resorcinol and formaldehyde.
AB  - The adsorption of four phenolic compounds (gallic acid, protocatechuic acid,
      vanillic acid and syringic acid) is investigated using a synthesized mesoporous
      carbon on both single and multi-component synthetic solutions. Some correlation
      of the adsorption capacity of the carbon and the nature of adsorbate could be
      made, except for gallic acid whose concentration decrease seems to be not
      exclusively due to adsorption but also to polymerization reaction. In the multi
      component mixture, negative effects in the adsorption capacity are observed
      probably due to competition for the active centers of the adsorbent surface. In
      desorption studies, ethanol presents better performance than water and
      acetonitrile. Vanillic acid is the compound with the higher adsorption and
      interestingly it is then possible to desorb a relatively high amount of it from
      the adsorbent, which may represent a possibility for a selective recovery of
      vanillic acid. These results present a potential way to treat the wastewater from
      the cork industry.

PMID- 29377829
TI  - Influence of temperature on the start-up of membrane bioreactor: kinetic study.
AB  - The start-up phase of a membrane bioreactor (MBR) for municipal wastewater
      treatment was studied to determine the effect of temperature on the organic
      matter removal and heterotrophic kinetics. The MBR system was analyzed during
      four start-up phases with values of hydraulic retention time (HRT) of 6 h and 10
      h, mixed liquor suspended solids (MLSS) concentrations of 4,000 mg L-1 and 7,000
      mg L-1 in the steady state, and temperature values of 11.5, 14.2, 22.9 and 30.1 
      degrees C. The influence of temperature on the biological process of organic
      matter removal was determined through the Arrhenius equation and Monod model. At
      the most favorable operation conditions of HRT (10 h) and MLSS (7,000 mg L-1)
      corresponding to phase 4, the effect of these variables dominated over the
      temperature. Heterotrophic biomass from phase 2 (HRT = 10 h, MLSS = 4,000 mg L-1
      and T = 30.1  degrees C) had the highest values of chemical oxygen demand (COD)
      degradation rate (rsu,H), implying less time to remove organic matter and shorter
      duration of the start-up phase.

PMID- 29377831
TI  - An intelligent detecting system for permeability prediction of MBR.
AB  - The membrane bioreactor (MBR) has been widely used to purify wastewater in
      wastewater treatment plants. However, a critical difficulty of the MBR is
      membrane fouling. To reduce membrane fouling, in this work, an intelligent
      detecting system is developed to evaluate the performance of MBR by predicting
      the membrane permeability. This intelligent detecting system consists of two main
      parts. First, a soft computing method, based on the partial least squares method
      and the recurrent fuzzy neural network, is designed to find the nonlinear
      relations between the membrane permeability and the other variables. Second, a
      complete new platform connecting the sensors and the software is built, in order
      to enable the intelligent detecting system to handle complex algorithms. Finally,
      the simulation and experimental results demonstrate the reliability and
      effectiveness of the proposed intelligent detecting system, underlying the
      potential of this system for the online membrane permeability for detecting
      membrane fouling of MBR.

PMID- 29377832
TI  - Natural treatment system models for wastewater management: a study from
      Hyderabad, India.
AB  - Wastewater generated on a global scale has become a significant source of water
      resources which necessitates appropriate management strategies. However, the
      complexities associated with wastewater are lack of economically viable treatment
      systems, especially in low- and middle-income countries. While many types of
      treatment systems are needed to serve the various local issues, we propose
      natural treatment systems (NTS) such as natural wetlands that are eco-friendly,
      cost-effective, and can be jointly driven by public bodies and communities. In
      order for it to be part of wastewater management, this study explores the NTS
      potential for removal of pollutants, cost-effectiveness, and reuse options for
      the 1.20 million m3/day of wastewater generated in Hyderabad, India. The pilot
      study includes hydro-geophysical characterization of natural wetland to determine
      pollutant removal efficiency and its effective utilization for treated wastewater
      in the peri-urban habitat. The results show the removal of organic content (76
      78%), nutrients (77-97%), and microbes (99.5-99.9%) from the wetland-treated
      wastewater and its suitability for agriculture applications. Furthermore, the
      wetland efficiency integrated with engineered interventions led to the
      development of NTS models with different application scenarios: (i) constructed
      wetlands, (ii) minimized community wetlands, and (iii) single outlet system,
      suitable for urban, peri-urban and rural areas, respectively.

PMID- 29377833
TI  - Evaluating the impacts of triclosan on wastewater treatment performance during
      startup and acclimation.
AB  - Triclosan (TCS) is a broad range antimicrobial agent used in many personal care
      products, which is commonly discharged to wastewater treatment facilities
      (WWTFs). This study examined the impact of TCS on wastewater treatment
      performance using laboratory bench-scale sequencing batch reactors (SBRs) coupled
      with anaerobic digesters. The SBRs were continuously fed synthetic wastewater
      amended with or without 0.68 MUM TCS, with the aim of determining the effect of
      chronic TCS exposure as opposed to a pulse TCS addition as previously studied.
      Overall, the present study suggests inhibition of nitrogen removal during reactor
      startup. However, NH4+ removal fully rebounded after 63 days, suggesting
      acclimation of the associated microbial communities to TCS. An initial decrease
      in microbial community diversity was observed in the SBRs fed TCS as compared to
      the control SBRs, followed by an increase in community diversity, which coincided
      with the increase in NH4+ removal. Elevated levels of NO3- and NO2- were found in
      the reactor effluent after day 58, however, suggesting ammonia oxidizing bacteria
      rebounding more rapidly than nitrogen oxidizing bacteria. Similar effects on
      treatment efficiencies at actual WWTFs have not been widely observed, suggesting
      that continuous addition of TCS in their influent may have selected for TCS
      resistant nitrogen oxidizing bacteria.

PMID- 29377834
TI  - Phenol biodegradation by isolated Citrobacter strain under hypersaline
      conditions.
AB  - Phenol is a toxic pollutant in many kinds of hypersaline industrial effluents
      that should be treated properly before discharged into water bodies. In this
      work, a halophilic strain which could utilize phenol as the sole source of carbon
      and energy was isolated. Based on 16S rRNA results, it was identified as a member
      of Citrobacter. The phenol biodegradation ability and cell growth of the strain
      was evaluated with the variation of initial phenol concentration and salinity.
      The effect of temperature and pH on phenol removal was also investigated. The
      results showed that the strain was capable of withstanding high phenol (up to
      1,100 mg L-1) environment with varying salinity conditions (0-10% of NaCl). The
      optimal initial phenol concentration was 400 mg L-1, at which the average removal
      rates of phenol peaked at 10.8 mg L-1 h-1. The higher initial concentration of
      phenol could inhibit the microbial metabolism. The optimal temperature, pH, and
      salinity were 35  degrees C, 6.0, and 0%, respectively. Under these conditions,
      400 mg L-1 of phenol could be completely degraded within 20 h. The high removal
      rates of phenol by the strain might provide an alternative for treating phenolic
      wastewaters containing high salinity.

PMID- 29377835
TI  - Rapid decolorization of textile wastewater by green synthesized iron
      nanoparticles.
AB  - The effectiveness of green tea (Camellia sinensis) and pomegranate (Punica
      granatum) extracts for the production of iron nanoparticles and their application
      for color removal from a textile industry wastewater was investigated.
      Polyphenols in extracts act as reducing agents for iron ions in aqueous
      solutions, forming iron nanoparticles. Pomegranate extract was found to have
      almost a 10-fold higher polyphenolic content than the same amount of green tea
      extract on a mass basis. However, the size of the synthesized nanoparticles did
      not show a correlation with the polyphenolic content. 100 ppm and 300 ppm of iron
      nanoparticles were evaluated in terms of color removal efficiency from a real
      textile wastewater sample. 300 ppm of pomegranate nanoscale zero-valent iron
      particles showed more than 95% color removal and almost 80% dissolved organic
      carbon removal. The degradation mechanisms are is considered to be adsorption and
      precipitation to a major extent, and mineralization to a minor extent.

PMID- 29377836
TI  - Virtual reality in urban water management: communicating urban flooding with
      particle-based CFD simulations.
AB  - For communicating urban flood risk to authorities and the public, a realistic
      three-dimensional visual display is frequently more suitable than detailed flood
      maps. Virtual reality could also serve to plan short-term flooding interventions.
      We introduce here an alternative approach for simulating three-dimensional
      flooding dynamics in large- and small-scale urban scenes by reaching out to
      computer graphics. This approach, denoted 'particle in cell', is a particle-based
      CFD method that is used to predict physically plausible results instead of
      accurate flow dynamics. We exemplify the approach for the real flooding event in
      July 2016 in Innsbruck.

PMID- 29377837
TI  - Removal of nitrate from water by acid-washed zero-valent iron/ferrous
      ion/hydrogen peroxide: influencing factors and reaction mechanism.
AB  - In this paper, a system consisting of acid-washed zero-valent iron (ZVI), ferrous
      ion (Fe2+), and hydrogen peroxide (H2O2) was employed for the removal of nitrate
      (NO3-) from water, and the reaction mechanism for this is discussed. The effects
      of acid-washed ZVI, Fe2+, H2O2, and initial NO3- concentration on nitrate removal
      were investigated. Acid-washed ZVI before and after reaction with nitrate were
      characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and
      X-ray photoelectron spectroscopy (XPS). Results reveal that the combined system
      can enhance the corrosion of ZVI and facilitate aqueous nitrate reduction. The
      products of nitrate reduction are mainly ammonium, with some N2. The ZVI
      particles after reaction may have a core of ZVI with an oxidation layer mainly
      consisting of Fe3O4.

PMID- 29377838
TI  - Characterizing health risks associated with recreational swimming at Taiwanese
      beaches by using quantitative microbial risk assessment.
AB  - Taiwan is surrounded by oceans, and therefore numerous pleasure beaches attract
      millions of tourists annually to participate in recreational swimming activities.
      However, impaired water quality because of fecal pollution poses a potential
      threat to the tourists' health. This study probabilistically characterized the
      health risks associated with recreational swimming engendered by waterborne
      enterococci at 13 Taiwanese beaches by using quantitative microbial risk
      assessment. First, data on enterococci concentrations at coastal beaches
      monitored by the Taiwan Environmental Protection Administration were reproduced
      using nonparametric Monte Carlo simulation (MCS). The ingestion volumes of
      recreational swimming based on uniform and gamma distributions were subsequently
      determined using MCS. Finally, after the distribution combination of the two
      parameters, the beta-Poisson dose-response function was employed to
      quantitatively estimate health risks to recreational swimmers. Moreover, various
      levels of risk to recreational swimmers were classified and spatially mapped to
      explore feasible recreational and environmental management strategies at the
      beaches. The study results revealed that although the health risks associated
      with recreational swimming did not exceed an acceptable benchmark of 0.019
      illnesses daily at all beaches, they approached to this benchmark at certain
      beaches. Beaches with relatively high risks are located in Northwestern Taiwan
      owing to the current movements.

PMID- 29377839
TI  - Adsorption of nitrate onto biochar derived from agricultural residuals.
AB  - To develop low-cost adsorbents for aqueous nitrate, biochars were prepared from
      three types of agricultural residuals at different pyrolysis temperatures (300 
      degrees C, 450  degrees C, and 600  degrees C). The corncob biochar produced at
      600  degrees C (CC600) was the best nitrate adsorbent of all the tested biochars.
      Characterization results showed that CC600 had good thermal stability, porous
      structure, and abundant surface functional groups. Findings from batch adsorption
      experiments demonstrated that CC600 showed relatively fast adsorption kinetics to
      nitrate in aqueous solutions. In addition, the Langmuir adsorption capacity of
      CC600 to nitrate was 14.46 mg/g, comparable to that of other biochar-based
      adsorbents. Therefore, CC600 showed promising potential to be used as a low-cost
      adsorbent for the treatment of nitrate in water.

PMID- 29377840
TI  - delta13CDIC tracing of dissolved inorganic carbon sources at Three Gorges
      Reservoir, China.
AB  - In order to understand water chemistry after impoundment of the Three Gorges
      Reservoir (TGR), the authors assessed the hydrogeochemical parameters (water
      temperature, pH, conductivity, dissolved O2), major element composition, and the
      carbon stable isotopic value of dissolved inorganic carbon (delta13CDIC) in
      summer and winter at various depths in the water column at TGR in 2009. In
      reservoir water, the DO values are lower in winter than in summer, but the pH
      values and conductivity values are higher. Ca2+ and Na+ are the dominant cations
      and HCO3- and SO42- are the dominant anions. In surface waters, the delta13CDIC
      values are more negative in summer than they are in winter, whereas the dissolved
      inorganic carbon (DIC) concentrations are relatively lower. In the water column,
      the DIC and delta13CDIC values do not change significantly with water depth or
      seasons. The DIC content shows a dilution effect in summer and is not modified by
      phytoplanktonic activity or photosynthesis. Even after the dam obstructed flow,
      the chemical profile of water in TGR is similar to that of the natural rivers
      before impoundment. Therefore, in this study, the water at TGR still had riverine
      characteristics and was still a heterotrophic system.

PMID- 29377841
TI  - Nomogram to Predict Graft Thickness in Descemet Stripping Automated Endothelial
      Keratoplasty: An Eye Bank Study.
AB  - PURPOSE: The purpose of this study was to develop a nomogram to predict postcut
      thickness of corneal grafts prepared at an eye bank for Descemet stripping
      automated endothelial keratoplasty (DSAEK). METHODS: Retrospective chart review
      was performed of DSAEK graft preparations by 3 experienced technicians from April
      2012 to May 2017 at the Eye Bank of Canada-Ontario Division. Variables collected
      included the following: donor demographics, death-to-preservation time, death-to
      processing time, precut tissue thickness, postcut tissue thickness, microkeratome
      head size, endothelial cell count, cut technician, and rate of perforation.
      Linear regression models were generated for each microkeratome head size (300 and
      350 MUm). RESULTS: A total of 780 grafts were processed during the study period.
      Twelve preparation attempts resulted in perforation (1.5%) and were excluded.
      Mean precut tissue thickness was 510 +/- 49 MUm (range: 363-670 MUm). Mean
      postcut tissue thickness was 114 +/- 22 MUm (range: 57-193 MUm). Seventy-nine
      percent (608/768) of grafts were <=130 MUm. The linear regression models included
      precut thickness and donor age, which were able to predict the thickness to
      within 25 MUm 80% of the time. CONCLUSIONS: We report a nomogram to predict
      thickness of DSAEK corneal grafts prepared in an eye bank setting, which was
      accurate to within 25 MUm 80% of the time. Other eye banks could consider
      performing similar analyses.

PMID- 29377842
TI  - Effects of Lipid- Versus Sodium Hyaluronate-Containing Eye Drops on Optical
      Quality and Ocular Surface Parameters as a Function of the Meibomian Gland
      Dropout Rate.
AB  - PURPOSE: To evaluate the effect of lipid- versus sodium hyaluronate-based eye
      drops on optical quality and ocular surface parameters. METHODS: Sixty eyes of 30
      patients with mild-to-moderate dry eye disease were included in a prospective
      randomized study. Each patient received either lipid- or sodium hyaluronate-based
      eye drops. Ocular symptom scores, breakup time, Schirmer test, fluorescein
      staining, noncontact meibography, and aberrometry were evaluated before and after
      3 months of therapy. RESULTS: At the 3-month visit, a statistically significant
      improvement (P <= 0.05) was noted in both groups on the Schirmer test, breakup
      time, ocular surface staining, and symptom score. In the lipid group, patients
      with progressive meibomian gland (MG) loss (>50%) showed a significantly greater
      increase in their corneal higher-order (HO) Strehl ratio (0.25 +/- 0.26 vs. -0.01
      +/- 0.25, P = 0.02) and modulation transfer function (MTF) (0.12 +/- 0.17 vs. 
      0.02 +/- 0.06, P = 0.03) than patients with less advanced MG disease. In the
      lipid group, a significant positive correlation was noted between the MG dropout
      rate and improvement in Schirmer values [Spearman correlation coefficient (CC):
      0.79], corneal HO Strehl (CC: 0.75), and HO modulation transfer function (CC:
      0.6), but a significant negative correlation was noted between the MG dropout
      rate and the HO root mean square (CC: -0.73). CONCLUSIONS: Lipid-containing
      artificial tears seem to be superior to sodium hyaluronate-containing drops in
      terms of improving HO aberrations and optical quality in patients with
      significant MG dysfunction.

PMID- 29377843
TI  - Reply.

PMID- 29377844
TI  - Reply.

PMID- 29377845
TI  - Osteomyelitis Arising Around Osseointegrated Dental Implants: A Systematic
      Review.
AB  - OBJECTIVE: The past few years have seen a progressive increment in the number of
      osteomyelitis cases associated with dental implants, raising the interest of a
      possible role of implant therapy in the development of osteomyelitis. The aim of
      the present study was to systematically review the association between dental
      implant therapy and occurrence of osteomyelitis. DATA SOURCES: The focused
      question addressed was "What is the risk to develop osteomyelitis among patients
      receiving dental implants?" Indexed databases were searched without language
      restrictions up to January 2017 using various key words including:
      "osteomyelitis"; "dental implants"; "osseointegration"; and "risk factors."
      RESULTS: Fourteen studies reporting cases of 39 patients who developed
      osteomyelitis after dental implant placement were identified. Among the 39
      patients, 66.6% were women and 28.2% were men. The overall mean age was 60.26
      years. Thirty-six patients had osteomyelitis of the mandible; 2 cases were
      reported in the maxilla, whereas, 1 case reported vertebral osteomyelitis
      associated with implant therapy. CONCLUSION: The knowledge of the real impact of
      osteomyelitis on the outcome of implant therapy and the identification of risk
      factors associated with this infectious and life-threatening condition are
      essential for the development of prevention protocols and treatment strategies.

PMID- 29377846
TI  - Is It Time to Reconsider Pressure Injuries as a Nurse-Sensitive Indicator?

PMID- 29377847
TI  - Building a Culture of Continuous Improvement and Employee Engagement Using a
      Daily Management System Part 1: Overview.
AB  - A daily management system (DMS) can be used to implement continuous quality
      improvement and advance employee engagement. It can empower staff to identify
      problems in the care environment that impact quality or workflow and to address
      them on a daily basis. Through DMS, improvement becomes the work of everyone,
      every day. The authors of this 2-part series describe their work to develop a
      DMS. Part 1 describes the background and organizing framework of the program.

PMID- 29377848
TI  - Metacognitive Interpersonal Therapy for Personality Disorders Featuring Emotional
      Inhibition: A Multiple Baseline Case Series.
AB  - Metacognitive interpersonal therapy (MIT) is an integrative psychotherapeutic
      approach targeting personality disorders (PDs) featuring inhibition and
      avoidance. The current case series reports the outcome of a time-limited, 12
      month MIT intervention for people with PDs featuring emotional inhibition. Seven
      participants were diagnosed with a PD on the basis of a structured clinical
      interview. The study followed a multiple baseline design, with baseline measures
      taken for 3 weeks before intervention. Participants underwent 12 months of weekly
      MIT sessions, with outcome measures taken every 3 months. Outcome variables were
      diagnostic recovery, symptom severity, and alexithymia. All participants improved
      over the course of the 12-month intervention across most measures. For six of the
      participants, the intervention was a likely driver of change. The current study
      contributes to a growing evidence base regarding the effectiveness of MIT for the
      treatment of PDs.

PMID- 29377849
TI  - ICD-11 Prevalence Rates of Posttraumatic Stress Disorder and Complex
      Posttraumatic Stress Disorder in a German Nationwide Sample.
AB  - Prevalence rates are still lacking for posttraumatic stress disorder (PTSD) and
      complex PTSD (CPTSD) diagnoses based on the new ICD-11 criteria. In a nationwide
      representative German sample (N = 2524; 14-99 years), exposure to traumatic
      events and symptoms of PTSD or CPTSD were assessed with the International Trauma
      Questionnaire. A clinical variant of CPTSD with a lower threshold for core PTSD
      symptoms was also calculated, in addition to conditional prevalence rates
      dependent on trauma type and differential predictors. One-month prevalence rates
      were as follows: PTSD, 1.5%; CPTSD, 0.5%; and CPTSD variant, 0.7%. For PTSD, the
      highest conditional prevalence was associated with kidnapping or rape, and the
      highest CPTSD rates were associated with sexual childhood abuse or rape. PTSD and
      CPTSD were best differentiated by sexual violence. Combined PTSD and CPTSD (ICD
      11) rates were in the range of previously reported prevalences for unified PTSD
      (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; ICD-10).
      Evidence on differential predictors of PTSD and CPTSD is still preliminary.

PMID- 29377850
TI  - Does the Angle of the Nail Matter for Pertrochanteric Fracture Reduction?
      Matching Nail Angle and Native Neck-Shaft Angle.
AB  - OBJECTIVES: To determine whether fixation of pertrochanteric hip fractures with
      cephalomedullary nails (CMNs) with a neck-shaft angle (NSA) less than the native
      NSA affects reduction and lag screw cutout. DESIGN: Retrospective comparative
      study. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Patients treated
      with a CMN for unstable pertrochanteric femur fractures (OTA/AO 31-A2.2 and 31
      A2.3) between 2005 and 2014. INTERVENTION: CMN fixation. MAIN OUTCOME
      MEASUREMENT: NSA reduction and lag screw cutout. RESULTS: Patients fixed with a
      nail angle less than their native NSA were less likely to have good reductions
      [17% vs. 60%, 95% confidence interval (CI), -63% to -18%; P = 0.0005], secondary
      to more varus reductions (41% vs. 10%, 95% CI, 9%-46%; P = 0.01) and more
      fractures with >=4 mm of displacement (63% vs. 35%, 95% CI, 3%-49%; P = 0.03).
      The cutout was not associated with the use of a nail angle less than the native
      NSA (60% vs. 76%, 95% CI, -56% to 18%; P = 0.5), varus reductions (60% vs. 32%,
      95% CI, -13% to 62%; P = 0.3), or poor reductions (20% vs. 17%, 95% CI, -24% to
      44%; P = 1.0). CONCLUSIONS: The fixation of unstable pertrochanteric hip
      fractures with a nail angle less than the native NSA was associated with more
      varus reductions and fracture displacement but did not affect the lag screw
      cutout. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 29377851
TI  - Leadership in Academic Medicine: Purpose, People, and Programs.

PMID- 29377852
TI  - At the Nexus of Academic and Social Change: The School for the Science of Health
      Care Delivery.

PMID- 29377853
TI  - Social Determinants of Health Education: A Call to Action.

PMID- 29377854
TI  - Remembering Thought Diversity: The Value of Social Science and Humanities
      Physician-Scholars in MD-PhD Programs.

PMID- 29377855
TI  - In Reply to Sun et al.

PMID- 29377856
TI  - Beyond Test Scores and Medical Knowledge: The Standardized Video Interview, an
      Innovative and Ethical Approach for Holistic Assessment of Applicants.

PMID- 29377857
TI  - Strategies for Residency Programs to Enhance Personal Relationships and Prevent
      Resident Burnout.

PMID- 29377859
TI  - Physician Advocacy: The Importance of Both Organizational and Individual Doctor
      Voices.

PMID- 29377858
TI  - In Reply to Wang and Myers.

PMID- 29377860
TI  - In Reply to Fisher.

PMID- 29377861
TI  - Artist's Statement: A Lady Between Two Majors.

PMID- 29377862
TI  - Missing the Gorilla.

PMID- 29377863
TI  - Room 604 - Ode to Orion.

PMID- 29377864
TI  - Commentary on "Room 604 - Ode to Orion".

PMID- 29377865
TI  - Validity Evidence for a Serious Game to Assess Performance on Critical Pediatric
      Emergency Medicine Scenarios.
AB  - INTRODUCTION: We developed a first-person serious game, PediatricSim, to teach
      and assess performances on seven critical pediatric scenarios (anaphylaxis,
      bronchiolitis, diabetic ketoacidosis, respiratory failure, seizure, septic shock,
      and supraventricular tachycardia). In the game, players are placed in the role of
      a code leader and direct patient management by selecting from various assessment
      and treatment options. The objective of this study was to obtain supportive
      validity evidence for the PediatricSim game scores. METHODS: Game content was
      developed by 11 subject matter experts and followed the American Heart
      Association's 2011 Pediatric Advanced Life Support Provider Manual and other
      authoritative references. Sixty subjects with three different levels of
      experience were enrolled to play the game. Before game play, subjects completed a
      40-item written pretest of knowledge. Game scores were compared between subject
      groups using scoring rubrics developed for the scenarios. Validity evidence was
      established and interpreted according to Messick's framework. RESULTS: Content
      validity was supported by a game development process that involved expert
      experience, focused literature review, and pilot testing. Subjects rated the game
      favorably for engagement, realism, and educational value. Interrater agreement on
      game scoring was excellent (intraclass correlation coefficient = 0.91, 95%
      confidence interval = 0.89-0.9). Game scores were higher for attendings followed
      by residents then medical students (Pc < 0.01) with large effect sizes (1.6-4.4)
      for each comparison. There was a very strong, positive correlation between game
      and written test scores (r = 0.84, P < 0.01). CONCLUSIONS: These findings
      contribute validity evidence for PediatricSim game scores to assess knowledge of
      pediatric emergency medicine resuscitation.

PMID- 29377866
TI  - Dexamethasone as an Adjuvant to Femoral Nerve Block in Children and Adolescents
      Undergoing Knee Arthroscopy: A Prospective, Randomized, Double-Blind, Placebo
      Controlled Trial.
AB  - BACKGROUND AND OBJECTIVES: Perineural dexamethasone has been demonstrated to
      extend postsurgical analgesia after peripheral nerve blockade in adults. The
      mechanism of action of dexamethasone as a regional anesthetic adjuvant is unclear
      as intravenous dexamethasone has been shown to have similar analgesic efficacy as
      perineural dexamethasone. The efficacy of perineural dexamethasone has not been
      previously explored in the pediatric population. METHODS: After obtaining
      informed consent, children (aged 10-18 years) presenting for arthroscopic knee
      surgery with a femoral nerve block were randomized to 1 of 3 groups: ropivacaine
      0.5% and intramuscular saline (group R), ropivacaine 0.5% plus perineural
      dexamethasone 0.1 mg/kg (maximum 4 mg) and intramuscular saline (group D), and
      ropivacaine 0.5% and intramuscular dexamethasone 0.1 mg/kg (maximum 4 mg) (group
      M). The primary outcome was the number of doses of analgesic agents in the first
      48 hours after hospital discharge. The number of doses was compared across study
      groups using Wilcoxon rank sum tests. RESULTS: Seventy-seven patients were
      enrolled in the study, of whom 4 were withdrawn because of additional surgical
      repair being performed, emergence delirium requiring unblinding, or loss to
      follow-up. The remaining 36 boys and 37 girls (aged 15 +/- 2 years) included 23
      patients randomized to group D, 23 patients randomized to group M, and 27
      patients randomized to group R. The median number of pain medication doses within
      48 hours of discharge was 2, 3, and 2 in groups D, M, and R, respectively. There
      were no significant differences in this outcome between groups D and M
      (difference in medians, 1; 95% confidence interval [CI] of difference in medians,
      -1 to 2; P = 0.475), groups D and R (difference in medians, 0; 95% CI of
      difference, -2 to 1; P = 0.821), or groups M and R (difference in medians, -1;
      95% CI of difference, -2 to 1; P = 0.594). Other secondary outcomes, including
      time to first analgesic consumption after discharge, visual analog scale pain
      score, and subjective intensity of motor block, did not evince statistically
      significant differences among the study groups. CONCLUSIONS: In the pediatric
      population, perineural or intramuscular dexamethasone did not improve analgesia
      after femoral nerve blockade for knee arthroscopy. Whether the observed lack of
      benefit reflects a true adult-pediatric difference or a limitation of the study
      could not be determined. Future pediatric studies are needed to evaluate
      dexamethasone for other block types and other types of surgery. CLINICAL TRIAL
      REGISTRATION: This study was registered at ClinicalTrials.gov, identifier
      NCT01971645.

PMID- 29377868
TI  - Characteristics of Adrenal Masses in Familial Adenomatous Polyposis.
AB  - BACKGROUND: Adrenal masses are a known extraintestinal manifestation of familial
      adenomatous polyposis. However, the literature on this association is largely
      confined to case reports. OBJECTIVE: This study aimed to determine the
      characteristics of adrenal masses in familial adenomatous polyposis and their
      clinical significance, as well as to estimate their prevalence. Mutational
      analysis was conducted to determine if any potential genotype-phenotype
      correlations exist. DESIGN: This is a retrospective cohort study. SETTING:
      Analysis included all patients meeting the criteria of classic familial
      adenomatous polyposis who were registered with the Familial Gastrointestinal
      Cancer Registry, a national Canadian database. PATIENTS: Appropriate imaging or
      autopsy reports were available in 311 registry patients. Patients with adrenal
      metastases were excluded. OUTCOME MEASURES: Data collection included demographic
      data, mutation genotype, adrenal mass characteristics, surgical interventions and
      mortality. RESULTS: The prevalence of adrenal masses was 16% (n = 48/311). The
      median age at diagnosis of adrenal mass was 45 years. The median diameter of
      adrenal mass at diagnosis was 1.7 cm (interquartile range, 1.4-3.0) with a median
      maximal diameter of 2.5 cm (interquartile range, 1.7-4.1) with median imaging
      follow-up of 48 months. The majority of adrenal masses were benign (97%, n =
      61/63). Surgery was performed on 7 patients because of concerns for size,
      malignancy, or hormonal secretion. One adrenal-related death was due to an
      adrenocortical carcinoma. Mutation analysis did not identify any specific
      genotype-phenotype correlations. LIMITATIONS: There were incomplete or
      insufficient endocrinology data available in the registry to allow for the
      analysis of hormone secretion patterns. CONCLUSIONS: Adrenal masses are
      approximately twice as prevalent in the familial adenomatous polyposis population
      as in previous studies of the general population. Nearly all mutations led to
      truncation of the APC gene; however, there was no genetic signature to help
      predict those at increased risk. The majority of adrenal lesions identified were
      of benign etiology; thus, an intensive management or surveillance strategy with
      imaging screening is likely unwarranted. See Video Abstract at
      http://links.lww.com/DCR/A507.

PMID- 29377869
TI  - Impact of Low Muscularity and Myosteatosis on Long-term Outcome After Curative
      Colorectal Cancer Surgery: A Propensity Score-Matched Analysis.
AB  - BACKGROUND: Muscle loss, characterized by reduced muscle mass (myopenia), and
      infiltration by intermuscular and intramuscular fat (myosteatosis), predicts a
      poor short-term prognosis in patients with colorectal cancer. However, little is
      known about the influence of myopenia and myosteatosis on long-term outcomes.
      OBJECTIVE: The present study aimed to evaluate the prognostic influence of both
      myopenia and myosteatosis on long-term outcomes after curative colorectal cancer
      surgery. DESIGN: This is a retrospective analysis using a propensity score
      matched analysis to reduce the possibility of selection bias. SETTINGS: The study
      was conducted at a single institution. PATIENTS: We performed a retrospective
      analysis of 211 consecutive patients with stage I to III colorectal cancer who
      underwent curative surgery between 2010 and 2011. INTERVENTION: CT scans were
      analyzed to calculate the lumbar skeletal muscle index and mean muscle
      attenuation using a SYNAPS VINCENT. MAIN OUTCOME MEASURES: The primary outcome
      measure was cancer-specific survival. Secondary end points included overall
      survival and disease-free survival. RESULTS: Of 211 patients, a total of 102 and
      106 were matched for myopenia and myosteatosis analyses. The median follow-up was
      57.6 months. Versus the nonmyopenia group, the myopenia group manifested a
      significantly shorter cancer-specific survival, overall survival, and disease
      free survival. Significantly shorter cancer-specific survival and overall
      survival times were also identified for the myosteatosis versus the
      nonmyosteatosis group. Before matching, multivariate analyses identified both
      myopenia and myosteatosis as independent prognostic factors for cancer-specific
      survival (p = 0.04 and p < 0.01), overall survival (p = 0.03 and p < 0.01), and
      disease-free survival (p < 0.01 and p < 0.01). LIMITATIONS: This study is limited
      by its retrospective, nonrandomized design. CONCLUSIONS: Myopenia and
      myosteatosis adversely affect long-term outcomes after curative colorectal cancer
      resection. See Video Abstract at http://links.lww.com/DCR/A463.

PMID- 29377870
TI  - The Ladd Procedure for Adult Malrotation With Volvulus.

PMID- 29377871
TI  - Symptom Severity and Quality of Life Among Long-term Colorectal Cancer Survivors
      Compared With Matched Control Subjects: A Population-Based Study.
AB  - BACKGROUND: Data are lacking regarding physical functioning, psychological well
      being, and quality of life among colorectal cancer survivors >10 years
      postdiagnosis. OBJECTIVE: The purpose of this study was to examine self-reported
      physical functioning, quality of life, and psychological well-being in long-term
      colorectal cancer survivors compared with age- and sex-matched unaffected control
      subjects. DESIGN: Participants completed a cross-sectional survey. SETTINGS: The
      colorectal cancer survivors and unaffected control subjects were recruited from
      the Ontario Familial Colorectal Cancer Registry. PATIENTS: A population-based
      sample of colorectal cancer survivors (N = 296) and their age- and sex-matched
      unaffected control subjects (N = 255) were included. Survivors were, on average,
      15 years postdiagnosis. MAIN OUTCOME MEASURES: Quality of life was measured with
      the Functional Assessment of Cancer Therapy-General scale, bowel dysfunction with
      the Memorial Sloan-Kettering Cancer Center scale, urinary dysfunction with the
      International Consultation on Incontinence Questionnaire-Short Form, fatigue with
      the Functional Assessment of Chronic Illness Therapy-Fatigue scale, and
      depression with the Center for Epidemiologic Studies-Depression scale. RESULTS:
      In linear mixed-model analyses adjusting for income, education, race, and
      comorbid medical conditions, survivors reported good emotional, functional,
      physical, and overall quality of life, comparable to control subjects. Fatigue
      and urinary functioning did not differ significantly between survivors and
      control subjects. Survivors reported significantly higher social quality of life
      and lower depression compared with unaffected control subjects. The only area
      where survivors reported significantly worse deficits was in bowel dysfunction,
      but the magnitude of differences was relatively small. LIMITATIONS:
      Generalizability is limited by moderately low participation rates. Findings are
      likely biased toward healthy participants. No baseline assessment was available
      to examine change in outcomes over time. CONCLUSIONS: Long-term colorectal cancer
      survivors appear to have comparable quality of life and, in some areas, better
      well-being than their unaffected peers. Bowel dysfunction may continue to be an
      ongoing issue even 15 years after colorectal cancer diagnosis. Overall quality of
      life can be expected to be good in this group of older survivors. See Video
      Abstract at http://links.lww.com/DCR/A476.

PMID- 29377872
TI  - Systematic Review and Meta-analysis of Objective Assessment of Physical Fitness
      in Patients Undergoing Colorectal Cancer Surgery.
AB  - BACKGROUND: Gas exchange-derived variables obtained from cardiopulmonary exercise
      testing allow objective assessment of functional capacity and hence physiological
      reserve to withstand the stressors of major surgery. Field walk tests provide an
      alternate means for objective assessment of functional capacity that may be
      cheaper and have greater acceptability, in particular, in elderly patients.
      OBJECTIVE: This systematic review evaluated the predictive value of
      cardiopulmonary exercise testing and field walk tests in surgical outcomes after
      colorectal surgery. DATA SOURCE: A systematic search was undertaken using
      Medline, PubMed, Embase, CINAHL, and PEDro. STUDY SELECTION: Adult patients who
      had cardiopulmonary exercise testing and/or field walk test before colorectal
      surgery were included. MAIN OUTCOME MEASURE: The primary outcomes measured were
      hospital length of stay and postoperative morbidity and mortality. RESULTS: A
      total of 7 studies with a cohort of 1418 patients who underwent colorectal
      surgery were identified for inclusion in a qualitative analysis. Both pooled
      oxygen consumption at anaerobic threshold (range, 10.1-11.1 mL.kg.min) and peak
      oxygen consumption (range, 16.7-18.6 mL.kg.min) were predictive of complications
      (OR for anaerobic threshold, 0.76; 95% CI, 0.66-0.85, p<0.0001; OR for peak
      oxygen consumption, 0.76; 95% CI, 0.67-0.85, p<0.0001). Patients had significant
      increased risk of developing postoperative complications if their anaerobic
      threshold was below this cut point (p<0.001). However, it was not predictive of
      anastomotic leak (p = 0.644). Shorter distance (<250 m) walked in incremental
      shuttle walk test, lower anaerobic threshold, and lower peak oxygen consumption
      were associated with prolonged hospital length of stay, which was closely related
      to the development of complications. CONCLUSIONS: Variables derived from
      cardiopulmonary exercise testing are predictive of postoperative complications
      and hospital length of stay. Currently, there are insufficient data to support
      the predictive role of the field walk test in colorectal surgery.

PMID- 29377873
TI  - Arc of Riolan-Preserving Splenic Flexure Takedown During Anterior Resection:
      Potentially Critical to Prevent Acute Anastomotic Ischemia.
AB  - INTRODUCTION: The Arc of Riolan is a strategic vessel that provides collateral
      mesenteric circulation in 10% of individuals. The importance of identifying and
      preserving the arc of Riolan in reducing the risk of ischemia to the proximal
      anastomotic segment after high ligation anterior resection was evaluated.
      TECHNIQUE: The arc of Riolan is a vessel that crosses anterior to the inferior
      mesenteric vein horizontally below the level of the pancreas. A retrospective
      review of all recorded videos of laparoscopic and robotic low and ultra-low
      anterior resections was performed in September to December 2012 and prospective
      evaluation in April to July 2013. The main outcome measures were arc of Riolan
      identification and preservation, and this was correlated with postoperative
      transmural colonic ischemia requiring surgical reintervention. From July 2013
      onward, we routinely performed arc of Riolan-sparing anterior resections.
      RESULTS: Arc of Riolan was observed in 17.8% of cases. Between 2006 and 2012,
      before routinely looking for and preserving the arc of Riolan, our rate of acute
      colonic transmural ischemia requiring an emergency Hartmann procedure after
      anterior resection was 0.8% (6/723). Between 2012 and 2016, after we started
      performing arc of Riolan-sparing splenic flexure takedown, there were no cases of
      acute colonic transmural ischemia requiring surgical reintervention (0/576) after
      anterior resection. CONCLUSIONS: Recognizing and preserving the arc of Riolan, if
      visualized, during high inferior mesenteric vein ligation and splenic flexure
      takedown may be an important step in reducing the risk of acute colonic ischemia
      postanterior resection. See Video at http://links.lww.com/DCR/A535.

PMID- 29377874
TI  - Successful Sequential Liver and Hematopoietic Stem Cell Transplantation in a
      Child With CD40 Ligand Deficiency and Cryptosporidium-Induced Liver Cirrhosis.
AB  - BACKGROUND: Hematopoietic stem cell transplantation (HSCT) is curative in
      patients with primary immunodeficiencies. However, pre-HSCT conditioning entails
      unacceptably high risks if the liver is compromised. The presence of a recurrent
      opportunistic infection affecting the biliary tree and determining liver
      cirrhosis with portal hypertension posed particular decisional difficulties in a
      7-year-old child with X-linked CD40-ligand deficiency. We aim at adding to the
      scanty experience available on such rare cases, as successful management with
      sequential liver transplantation (LT) and HSCT has been reported in detail only
      in 1 young adult to date. METHODS: A closely sequential strategy, with a surgical
      complication-free LT, followed by reduced-intensity conditioning, allowed HSCT to
      be performed only one month after LT, preventing Cryptosporidium parvum
      recolonization of the liver graft. RESULTS: Combined sequential LT and HSCT
      resolved the cirrhotic evolution and corrected the immunodeficiency so that the
      infection responsible for the progressive sclerosing cholangitis did not recur.
      CONCLUSIONS: Hopefully, this report of the successful resolution of a potentially
      fatal combination of immunodeficiency and chronic opportunistic infection with
      end-stage organ damage in a child will encourage others to adapt a sequential
      transplant approach to this highly complex pathology. However, caution is to be
      exercised to carefully balance the risks intrinsic to transplant surgery and
      immunosuppression in primary immunodeficiencies.

PMID- 29377867
TI  - Site Variability in Regulatory Oversight for an International Study of Pediatric
      Sepsis.
AB  - OBJECTIVES: Duplicative institutional review board/research ethics committee
      review for multicenter studies may impose administrative burdens and
      inefficiencies affecting study implementation and quality. Understanding
      variability in site-specific institutional review board/research ethics committee
      assessment and barriers to using a single review committee (an increasingly
      proposed solution) can inform a more efficient process. We provide needed data
      about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and
      Therapies multicenter point prevalence study. DESIGN: Survey. SETTING: Sites
      invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. SUBJECTS:
      Investigators at sites that expressed interest and/or participated in Sepsis
      PRevalence, OUtcomes, and Therapies. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Using an electronic survey, we collected data about 1) logistics of
      protocol submission, 2) institutional review board/research ethics committee
      requested modifications, and 3) use of a single institutional review board (for
      U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites
      that submitted the protocol for institutional review board/research ethics
      committee review, 34% conducted full board review, 54% expedited review, and 4%
      considered the study exempt. Time to institutional review board/research ethics
      committee approval required a median of 34 (range 3-186) days, which took longer
      at sites that required protocol modifications (median [interquartile range] 50 d
      [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites
      due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered
      using a single institutional review board, but only 18% utilized this option.
      Time to final approval for U.S. sites using the single institutional review board
      was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile
      range, 15-54 d) for nonsingle institutional review board sites (p = 0.16).
      CONCLUSIONS: Variability in regulatory oversight was evident for this minimal
      risk observational research study, most notably in the category of type of review
      conducted. Duplicative review prolonged time to protocol approval at some sites.
      Use of a single institutional review board for U.S. sites was rare and did not
      improve efficiency of protocol approval. Suggestions for minimizing these
      challenges are provided.

PMID- 29377875
TI  - Novel TOF-MS Means of Quantifying ApoAI Amyloid Protein Load After Combined Liver
      Kidney Transplantation.

PMID- 29377876
TI  - Gender, Race and Disease Etiology Predict De Novo Malignancy Risk following Liver
      Transplantation: Insights for Future Individualized Cancer Screening Guidance.
AB  - BACKGROUND: Malignancy after liver transplant (LT) is a leading cause of
      mortality, but data is limited. The aim of this study was to identify patients at
      higher risk for de novo malignancies after LT in a large multicenter database.
      METHODS: The Scientific Registry of Transplant Recipients database comprising all
      108,412 liver transplant recipients across the U.S. between 1987 and March 2015
      was analyzed with a median follow-up of 6.95 years. Potential risk factors for
      malignancies after LT were assessed using Cox regression analysis for the outcome
      of time to first malignancy. RESULTS: Mean age 51.9 +/- 10.8 years, 64.6% male,
      74.5% Caucasian, and 15.8% with previous malignancy. Malignancies during follow
      up were 4,483 (41.3%) skin, 1,519 (14.0%) hematologic, and 4,842 (44.7%) solid
      organ. The 10-year probability of de novo malignancy was 11.5% (11.3-11.8%). On
      multivariable analysis, age by decade (HR 1.52; p<0.001), male gender (HR 1.28;
      p<0.001), Caucasian race (compared to other races, HR 1.45-2.04; p<0.001),
      multiorgan transplant (HR 1.35; p<0.001), previous malignancy (HR 1.34; p<0.001)
      and alcoholic liver disease, autoimmune, Nonalcoholic steatohepatitis (HR 1.35;
      p<0.001), and Primary Sclerosing Cholangitis pre-LT (compared to HCV, p<0.001)
      were associated with higher risk of post-LT malignancy, but type of
      immunosuppression was not (p=NS). CONCLUSIONS: This large dataset demonstrates
      the effects of ethnicity/race and etiologies of liver disease, particularly NASH
      as additional risk factors for cancer after LT. Patients with these high-risk
      characteristics should be more regularly and diligently screened.

PMID- 29377877
TI  - Incidence of Cytomegalovirus DNAemia in Pediatric Kidney Transplant Recipients
      After Cessation of Antiviral Prophylaxis.
AB  - BACKGROUND: Late cytomegalovirus (CMV) infection can occur after cessation of
      viral prophylaxis in kidney transplant recipients, yet, timing of infection is
      unclear and longer duration of prophylaxis may be warranted. METHODS: We
      conducted a retrospective cohort study of 86 children (35 CMV donor seropositive,
      recipient seronegative [D + R-] and 51 CMV recipient seropositive [R+]) younger
      than 18 years who received a kidney transplant between January 2002 and June 2014
      and were treated with antiviral prophylaxis for 3 months after transplantation.
      Incidence of CMV DNAemia and CMV disease was determined using Kaplan-Meier
      analyses and risk factors were assessed using Poisson regression. RESULTS: Of the
      86 children, 61.6% were male and median age at transplant was 13.4 years
      (interquartile range [IQR], 8.9-15.6) with a median follow-up of 35.2 months
      (IQR, 18.0-54.5). Incidence of CMV DNAemia within the first 3 months after
      prophylaxis cessation in CMV D + R- and CMV R+ children was 22.9% and 23.5% and
      incidence of CMV disease was 11.4% and 0%, respectively. Cumulative incidence of
      CMV DNAemia in both groups was similar (31.4%). Children who received
      antithymocyte globulin were more likely to develop CMV DNAemia compared with
      those who received anti-IL-2 (IRR, 2.98; 95% confidence interval, 1.41-6.30)
      after controlling for age, sex, Epstein-Barr Virus serostatus and rejection.
      CONCLUSIONS: This study demonstrates a high incidence of CMV infection after
      cessation of antiviral prophylaxis. These results support extension of antiviral
      prophylaxis beyond 3 months and/or intensive viral load monitoring to reduce risk
      of CMV infection in D + R- and R+ children, especially those receiving
      antithymocyte globulin.

PMID- 29377878
TI  - Implementing Endobronchial Ultrasound-Guided (EBUS) for Staging and Diagnosis of
      Lung Cancer: A Cost Analysis.
AB  - BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS
      TBNA) and guide sheath (EBUS-GS) are gaining popularity for diagnosis and staging
      of lung cancer compared to CT-guided transthoracic needle aspiration (CT-TTNA),
      blind fiber-optic bronchoscopy, and mediastinoscopy. This paper aimed to examine
      predictors of higher costs for diagnosing and staging lung cancer, and to assess
      the effect of EBUS techniques on hospital cost. MATERIAL AND METHODS Hospital
      costs for diagnosis and staging of new primary lung cancer patients presenting in
      2007-2008 and 2010-2011 were reviewed retrospectively. Multiple linear regression
      was used to determine relationships with hospital cost. RESULTS We reviewed 560
      lung cancer patient records; 100 EBUS procedures were performed on 90 patients.
      Higher hospital costs were associated with: EBUS-TBNA performed (p<0.0001);
      increasing inpatient length of stay (p<0.0001); increasing number of other
      surgical/diagnostic procedures (p<0.0001); whether the date of management
      decision fell within an inpatient visit (p<0.0001); and if the patient did not
      have a CT-TTNA, then costs increased as the number of imaging events increased
      (interaction p<0.0001). Cohort was not significantly related to cost. Location of
      the procedure (outside vs. inside theater) was a predictor of lower one-day EBUS
      costs (p<0.0001). Cost modelling revealed potential cost saving of $1506 per EBUS
      patient if all EBUS procedures were performed outside rather than in the theater
      ($66,259 per annum). CONCLUSIONS EBUS-TBNA only was an independent predictor of
      higher cost for diagnosis and staging of lung cancer. Performing EBUS outside
      compared to in the theater may lower costs for one-day procedures; potential
      future savings are considerable if more EBUS procedures could be performed
      outside the operating theater.

PMID- 29377880
TI  - Evaluation of oxfendazole in the treatment of zoonotic Onchocerca lupi infection
      in dogs.
AB  - The genus Onchocerca encompasses parasitic nematodes including Onchocerca
      volvulus, causative agent of river blindness in humans, and the zoonotic
      Onchocerca lupi infecting dogs and cats. In dogs, O. lupi adult worms cause
      ocular lesions of various degrees while humans may bear the brunt of zoonotic
      onchocercosis with patients requiring neurosurgical intervention because of
      central nervous system localization of nematodes. Though the zoonotic potential
      of O. lupi has been well recognized from human cases in Europe, the United States
      and the Middle East, a proper therapy for curing this parasitic infection in dogs
      is lacking. To evaluate the efficacy of oxfendazole, 11 out of the 21 client
      owned dogs (21/123; 17.1%) positive for skin-dwelling O. lupi microfilariae
      (mfs), were enrolled in the efficacy study and were treated with oxfendazole (50
      mg/kg) per OS once a day for 5 (G2) or 10 (G3) consecutive days or were left
      untreated (G1). The efficacy of oxfendazole in the reduction of O. lupi mfs was
      evaluated by microfilarial count and by assessing the percentage of mfs reduction
      and mean microfilaricidal efficacy, whereas the efficacy in the reduction of
      ocular lesions was evaluated by ultrasound imaging. All dogs where subjected to
      follow-ups at 30 (D30), 90 (D90) and 180 (D180) days post-treatment. The
      percentage of reduction of mfs was 78% for G2 and 12.5% for G3 at D180. The mean
      microfilaricidal efficacy of oxfendazole in the treatment of canine onchocercosis
      by O. lupi at D30, D90 and D180 was 41%, 81% and 90%, in G2 and 40%, 65% and 70%,
      in G3, respectively. Retrobulbar lesions did not reduce from D0 to D180 in
      control group (dogs in G1), whereas all treated dogs (in G2 and G3) had slightly
      decreased ocular lesions. Percentage of reduction of ocular lesions by ultrasound
      examination was 50% and 47.5% in G2 and G3 at D180, respectively. Despite the
      decrease in ocular lesions in all treated dogs (G2 and G3), oxfendazole was
      ineffective in reducing ocular lesions and skin-dwelling O. lupi mfs in treated
      dogs (G2 and G3) in a six-month follow-up period. Here we discuss the need for
      more reliable diagnostic techniques and efficient treatment protocols to better
      plan future intervention strategies.

PMID- 29377881
TI  - PD-L1 checkpoint inhibition and anti-CTLA-4 whole tumor cell vaccination counter
      adaptive immune resistance: A mouse neuroblastoma model that mimics human
      disease.
AB  - BACKGROUND: Adaptive immune resistance induces an immunosuppressive tumor
      environment that enables immune evasion. This phenomenon results in tumor escape
      with progression and metastasis. Programmed cell death-ligand 1 (PD-L1) expressed
      on tumors is thought to inhibit tumor-infiltrating lymphocytes (TILs) through
      programmed cell death 1 (PD1), enabling adaptive immune resistance. This study
      investigates the role of PD-L1 in both mouse and human neuroblastoma immunity.
      The consequence of PD-L1 inhibition is characterized in the context of an
      established whole tumor cell vaccine. METHODS AND FINDINGS: A mouse model of
      neuroblastoma was investigated using an Id2 knockdown whole cell vaccine in
      combination with checkpoint inhibition. We show that immunogenic mouse
      neuroblastoma acquires adaptive immune resistance by up-regulating PD-L1
      expression, whereas PD-L1 is of lesser consequence in nonimmunogenic
      neuroblastoma tumors. Combining PD-L1 checkpoint inhibition with whole tumor
      cell/anti-CTLA-4 vaccination enhanced tumor cell killing, cured mice with
      established tumors, and induced long-term immune memory (6 months). From an
      evaluation of patient neuroblastoma tumors, we found that the inflammatory
      environment of the mouse neuroblastoma mimicked human disease in which PD-L1
      expression was associated directly with TILs and lower-risk tumors. High-risk
      patient tumors were lacking both TILs and PD-L1 expression. Although a
      correlation in immunity seems to exist between the mouse model and human
      findings, the mouse tumor model is induced and not spontaneously occurring, and
      furthermore, the number of both mouse and human correlates is limited.
      CONCLUSIONS: This study demonstrates the role PD-L1 plays in neuroblastoma's
      resistance to immunity and defines the nonredundant effect of combination
      checkpoint inhibition with vaccine therapy in a mouse model. High-risk,
      nonimmunogenic human tumors display both diminished PD-L1 expression and adaptive
      immune resistance. Paradoxically, high-risk tumors may be more responsive to
      effective vaccine therapy because of their apparent lack of adaptive immune
      resistance.

PMID- 29377883
TI  - The importance of being second.

PMID- 29377882
TI  - Dried Blood Spots for Measuring Vibrio cholerae-specific Immune Responses.
AB  - BACKGROUND: Vibrio cholerae causes over 2 million cases of cholera and 90,000
      deaths each year. Serosurveillance can be a useful tool for estimating the
      intensity of cholera transmission and prioritizing populations for cholera
      control interventions. Current methods involving venous blood draws and
      downstream specimen storage and transport methods pose logistical challenges in
      most settings where cholera strikes. To overcome these challenges, we developed
      methods for determining cholera-specific immune responses from dried blood spots
      (DBS). METHODOLOGY/PRINCIPAL FINDINGS: As conventional vibriocidal assay methods
      were unsuitable for DBS eluates from filter paper, we adopted a drop-plate
      culture method. We show that DBS collected from volunteers in South Sudan, and
      stored for prolonged periods in field conditions, retained functional vibriocidal
      antibodies, the titers of which correlated with paired serum titers determined by
      conventional spectrophotometric methods (r = 0.94, p = 0.00012). We also showed
      that eluates from DBS Serum Separator cards could be used with conventional
      spectrophotometric vibriocidal methods, and that they correlated with paired
      serum at a wide range of titers (r = 0.96, p<0.0001). Similarly, we used ELISA
      methods to show that V. cholerae O-specific polysaccharide antibody responses
      from DBS eluates correlated with results from paired serum for IgG (r = 0.85, p =
      0.00006), IgM (r = 0.79, p = 0.00049) and IgA (r = 0.73, p = 0.0019),
      highlighting its potential for use in determination of isotype-specific
      responses. Storage of DBS cards at a range of temperatures did not change
      antibody responses. CONCLUSION: In conclusion, we have developed and demonstrated
      a proof-of-concept for assays utilizing DBS for assessing cholera-specific immune
      responses.

PMID- 29377879
TI  - Expert consensus document: Clinical and molecular diagnosis, screening and
      management of Beckwith-Wiedemann syndrome: an international consensus statement.
AB  - Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is
      characterized by phenotypic variability that might include overgrowth,
      macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized
      overgrowth and predisposition to embryonal tumours. Delineation of the molecular
      defects within the imprinted 11p15.5 region can predict familial recurrence risks
      and the risk (and type) of embryonal tumour. Despite recent advances in
      knowledge, there is marked heterogeneity in clinical diagnostic criteria and
      care. As detailed in this Consensus Statement, an international consensus group
      agreed upon 72 recommendations for the clinical and molecular diagnosis and
      management of BWS, including comprehensive protocols for the molecular
      investigation, care and treatment of patients from the prenatal period to
      adulthood. The consensus recommendations apply to patients with Beckwith
      Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis
      and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the
      consensus group recommends a tumour surveillance programme targeted by molecular
      subgroups, surveillance might differ according to the local health-care system
      (for example, in the United States), and the results of targeted and universal
      surveillance should be evaluated prospectively. International collaboration,
      including a prospective audit of the results of implementing these consensus
      recommendations, is required to expand the evidence base for the design of
      optimum care pathways.

PMID- 29377884
TI  - Estimating Cryptosporidium and Giardia disease burdens for children drinking
      untreated groundwater in a rural population in India.
AB  - BACKGROUND: In many low-income settings, despite improvements in sanitation and
      hygiene, groundwater sources used for drinking may be contaminated with enteric
      pathogens such as Cryptosporidium and Giardia, which remain important causes of
      childhood morbidity. In this study, we examined the contribution of diarrhea
      caused by Cryptosporidium and Giardia found in groundwater sources used for
      drinking to the total burden of diarrheal disease among children < 5 in rural
      India. METHODOLOGY/PRINCIPAL FINDINGS: We studied a population of 3,385 children
      < 5 years of age in 100 communities of Puri District, Odisha, India. We developed
      a coupled quantitative microbial risk assessment (QMRA) and susceptible-infected
      recovered (SIR) population model based on observed levels of Cryptosporidium and
      Giardia in improved groundwater sources used for drinking and compared the QMRA
      SIR estimates with independently measured all-cause (i.e., all fecal-oral enteric
      pathogens and exposure pathways) child diarrhea prevalence rates observed in the
      study population during two monsoon seasons (2012 and 2013). We used site
      specific and regional studies to inform assumptions about the human pathogenicity
      of the Cryptosporidium and Giardia species present in local groundwater. In all
      three human pathogenicity scenarios evaluated, the mean daily risk of
      Cryptosporidium or Giardia infection (0.06-1.53%), far exceeded the tolerable
      daily risk of infection from drinking water in the US (< 0.0001%). Depending on
      which protozoa species were present, median estimates of daily child diarrhea
      prevalence due to either Cryptosporidium or Giardia infection from drinking water
      was as high as 6.5% or as low as < 1% and accounted for at least 2.9% and as much
      as 65.8% of the all-cause diarrhea disease burden measured in children < 5 during
      the study period. Cryptosporidium tended to account for a greater share of
      estimated waterborne protozoa infections causing diarrhea than did Giardia.
      Diarrhea prevalence estimates for waterborne Cryptosporidium infection appeared
      to be most sensitive to assumptions about the probability of infection from
      ingesting a single parasite (i.e. the rate parameter in dose-response model),
      while Giardia infection was most sensitive to assumptions about the viability of
      parasites detected in groundwater samples. CONCLUSIONS/SIGNIFICANCE: Protozoa in
      groundwater drinking sources in rural India, even at low concentrations,
      especially for Cryptosporidium, may account for a significant portion of child
      diarrhea morbidity in settings were tubewells are used for drinking water and
      should be more systematically monitored. Preventing diarrheal disease burdens in
      Puri District and similar settings will benefit from ensuring water is
      microbiologically safe for consumption and consistent and effective household
      water treatment is practiced.

PMID- 29377885
TI  - WRKY23 is a component of the transcriptional network mediating auxin feedback on
      PIN polarity.
AB  - Auxin is unique among plant hormones due to its directional transport that is
      mediated by the polarly distributed PIN auxin transporters at the plasma
      membrane. The canalization hypothesis proposes that the auxin feedback on its
      polar flow is a crucial, plant-specific mechanism mediating multiple self
      organizing developmental processes. Here, we used the auxin effect on the PIN
      polar localization in Arabidopsis thaliana roots as a proxy for the auxin
      feedback on the PIN polarity during canalization. We performed microarray
      experiments to find regulators of this process that act downstream of auxin. We
      identified genes that were transcriptionally regulated by auxin in an AXR3/IAA17-
      and ARF7/ARF19-dependent manner. Besides the known components of the PIN
      polarity, such as PID and PIP5K kinases, a number of potential new regulators
      were detected, among which the WRKY23 transcription factor, which was
      characterized in more detail. Gain- and loss-of-function mutants confirmed a role
      for WRKY23 in mediating the auxin effect on the PIN polarity. Accordingly,
      processes requiring auxin-mediated PIN polarity rearrangements, such as vascular
      tissue development during leaf venation, showed a higher WRKY23 expression and
      required the WRKY23 activity. Our results provide initial insights into the auxin
      transcriptional network acting upstream of PIN polarization and, potentially,
      canalization-mediated plant development.

PMID- 29377886
TI  - Molecular epidemiology of dengue viruses in three provinces of Lao PDR, 2006
      2010.
AB  - Few data on dengue epidemiology are available for Lao PDR. Here, we provide
      information on the complexity of dengue epidemiology in the country,
      demonstrating dynamic circulation that varies over space and time, according to
      serotype. We recruited 1,912 consenting patients presenting with WHO dengue
      criteria at Mahosot Hospital, Vientiane (central Laos), between 2006 and 2010.
      Between 2008 and 2010, 1,413 patients with undifferentiated fever were also
      recruited at Luang Namtha (LNT) Provincial Hospital (northern Laos) and 555 at
      Salavan (SV) Provincial Hospital (southern Laos). We report significant
      variations in Dengue virus (DENV) circulation between the three sites. Peaks of
      DENV infection were observed in the rainy seasons, although 11% of confirmed
      cases in the provinces and 4.6% in the capital were detected during the dry and
      cool seasons (between December and February). Four DENV serotypes were detected
      among the 867 RT-PCR positive patients: 76.9% DENV-1, 9.6% DENV-2, 7.7% DENV-4
      and 5.3% DENV-3. DENV-1 was the predominant serotype throughout the study except
      in LNT in 2008 and 2009 when it was DENV-2. Before July 2009, DENV-2 was not
      detected in SV and only rarely detected in Vientiane. DENV-3 and DENV-4 were
      commonly detected in Vientiane, before 2008 for DENV-4 and after 2009 for DENV-3.
      The phylogenetic analyses of DENV envelope sequences suggest concurrent multiple
      introductions of new strains as well as active DENV circulation throughout Laos
      and with neighboring countries. It is therefore of great importance to develop
      and strengthen a year-round nation-wide surveillance network in order to collect
      data that would allow anticipation of public health issues caused by the
      occurrence of large dengue outbreaks.

PMID- 29377887
TI  - Identification of allosteric inhibitors of the ecto-5'-nucleotidase (CD73)
      targeting the dimer interface.
AB  - The ecto-5'-nucleotidase CD73 plays an important role in the production of immune
      suppressive adenosine in tumor micro-environment, and has become a validated drug
      target in oncology. Indeed, the anticancer immune response involves extracellular
      ATP to block cell proliferation through T-cell activation. However, in the tumor
      micro-environment, two extracellular membrane-bound enzymes (CD39 and CD73) are
      overexpressed and hydrolyze efficiently ATP into AMP then further into immune
      suppressive adenosine. To circumvent the impact of CD73-generated adenosine, we
      applied an original bioinformatics approach to identify new allosteric inhibitors
      targeting the dimerization interface of CD73, which should impair the large
      dynamic motions required for its enzymatic function. Several hit compounds issued
      from virtual screening campaigns showed a potent inhibition of recombinant CD73
      with inhibition constants in the low micromolar range and exhibited a non
      competitive inhibition mode. The structure-activity relationships studies
      indicated that several amino acid residues (D366, H456, K471, Y484 and E543 for
      polar interactions and G453-454, I455, H456, L475, V542 and G544 for hydrophobic
      contacts) located at the dimerization interface are involved in the tight binding
      of hit compounds and likely contributed for their inhibitory activity. Overall,
      the gathered information will guide the upcoming lead optimization phase that may
      lead to potent and selective CD73 inhibitors, able to restore the anticancer
      immune response.

PMID- 29377889
TI  - The differential impact of scientific quality, bibliometric factors, and social
      media activity on the influence of systematic reviews and meta-analyses about
      psoriasis.
AB  - Researchers are increasingly using on line social networks to promote their work.
      Some authors have suggested that measuring social media activity can predict the
      impact of a primary study (i.e., whether or not an article will be highly cited).
      However, the influence of variables such as scientific quality, research
      disclosures, and journal characteristics on systematic reviews and meta-analyses
      has not yet been assessed. The present study aims to describe the effect of
      complex interactions between bibliometric factors and social media activity on
      the impact of systematic reviews and meta-analyses about psoriasis (PROSPERO
      2016: CRD42016053181). Methodological quality was assessed using the Assessing
      the Methodological Quality of Systematic Reviews (AMSTAR) tool. Altmetrics, which
      consider Twitter, Facebook, and Google+ mention counts as well as Mendeley and
      SCOPUS readers, and corresponding article citation counts from Google Scholar
      were obtained for each article. Metadata and journal-related bibliometric indices
      were also obtained. One-hundred and sixty-four reviews with available altmetrics
      information were included in the final multifactorial analysis, which showed that
      social media and impact factor have less effect than Mendeley and SCOPUS readers
      on the number of cites that appear in Google Scholar. Although a journal's impact
      factor predicted the number of tweets (OR, 1.202; 95% CI, 1.087-1.049), the years
      of publication and the number of Mendeley readers predicted the number of
      citations in Google Scholar (OR, 1.033; 95% CI, 1.018-1.329). Finally,
      methodological quality was related neither with bibliometric influence nor social
      media activity for systematic reviews. In conclusion, there seems to be a lack of
      connectivity between scientific quality, social media activity, and article
      usage, thus predicting scientific success based on these variables may be
      inappropriate in the particular case of systematic reviews.

PMID- 29377888
TI  - Biophysical network modeling of the dLGN circuit: Effects of cortical feedback on
      spatial response properties of relay cells.
AB  - Despite half-a-century of research since the seminal work of Hubel and Wiesel,
      the role of the dorsal lateral geniculate nucleus (dLGN) in shaping the visual
      signals is not properly understood. Placed on route from retina to primary visual
      cortex in the early visual pathway, a striking feature of the dLGN circuit is
      that both the relay cells (RCs) and interneurons (INs) not only receive
      feedforward input from retinal ganglion cells, but also a prominent feedback from
      cells in layer 6 of visual cortex. This feedback has been proposed to affect
      synchronicity and other temporal properties of the RC firing. It has also been
      seen to affect spatial properties such as the center-surround antagonism of
      thalamic receptive fields, i.e., the suppression of the response to very large
      stimuli compared to smaller, more optimal stimuli. Here we explore the spatial
      effects of cortical feedback on the RC response by means of a a comprehensive
      network model with biophysically detailed, single-compartment and
      multicompartment neuron models of RCs, INs and a population of orientation
      selective layer 6 simple cells, consisting of pyramidal cells (PY). We have
      considered two different arrangements of synaptic feedback from the ON and OFF
      zones in the visual cortex to the dLGN: phase-reversed ('push-pull') and phase
      matched ('push-push'), as well as different spatial extents of the
      corticothalamic projection pattern. Our simulation results support that a phase
      reversed arrangement provides a more effective way for cortical feedback to
      provide the increased center-surround antagonism seen in experiments both for
      flashing spots and, even more prominently, for patch gratings. This implies that
      ON-center RCs receive direct excitation from OFF-dominated cortical cells and
      indirect inhibitory feedback from ON-dominated cortical cells. The increased
      center-surround antagonism in the model is accompanied by spatial focusing, i.e.,
      the maximum RC response occurs for smaller stimuli when feedback is present.

PMID- 29377890
TI  - Caregivers' views on stigmatization and discrimination of people affected by
      leprosy in Ghana.
AB  - BACKGROUND: Leprosy is a condition that has long been associated with stigma and
      discrimination, even when infected persons have been cured. This paper describes
      stigma and discrimination as viewed by caregivers who are associated with people
      affected by leprosy in Ghana. METHODS: A qualitative interview with semi
      structured interviews were conducted for twenty caregivers. RESULTS: Findings
      indicated that caregivers were of the view that people affected by leprosy in
      Ghana are stigmatized and discriminated against by the larger society thus making
      their movements and interactions restricted to the Leprosarium. Besides,
      employments opportunities are unavailable to them thus making them exposed to
      financial challenges. The livelihood Empowerment Against poverty (LEAP) money
      given them is not sufficient for their daily upkeep. CONCLUSION: People affected
      by leprosy in Ghana are stigmatized and therefore find it difficult to interact
      freely with the public. The associated physical deformities with the disease also
      tend to impede their ability to relate to the general public. The LEAP cash given
      to people affected by leprosy is helpful however, it could be enhanced to keep
      pace with prevailing economic conditions in the country.

PMID- 29377891
TI  - The development of a stochastic mathematical model of Alzheimer's disease to help
      improve the design of clinical trials of potential treatments.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder characterised by a slow
      progressive deterioration of cognitive capacity. Drugs are urgently needed for
      the treatment of AD and unfortunately almost all clinical trials of AD drug
      candidates have failed or been discontinued to date. Mathematical, computational
      and statistical tools can be employed in the construction of clinical trial
      simulators to assist in the improvement of trial design and enhance the chances
      of success of potential new therapies. Based on the analysis of a set of clinical
      data provided by the Alzheimer's Disease Neuroimaging Initiative (ADNI) we
      developed a simple stochastic mathematical model to simulate the development and
      progression of Alzheimer's in a longitudinal cohort study. We show how this
      modelling framework could be used to assess the effect and the chances of success
      of hypothetical treatments that are administered at different stages and delay
      disease development. We demonstrate that the detection of the true efficacy of an
      AD treatment can be very challenging, even if the treatment is highly effective.
      An important reason behind the inability to detect signals of efficacy in a
      clinical trial in this therapy area could be the high between- and within
      individual variability in the measurement of diagnostic markers and endpoints,
      which consequently results in the misdiagnosis of an individual's disease state.

PMID- 29377892
TI  - Network-based co-expression analysis for exploring the potential diagnostic
      biomarkers of metastatic melanoma.
AB  - Metastatic melanoma is an aggressive skin cancer and is one of the global
      malignancies with high mortality and morbidity. It is essential to identify and
      verify diagnostic biomarkers of early metastatic melanoma. Previous studies have
      systematically assessed protein biomarkers and mRNA-based expression
      characteristics. However, molecular markers for the early diagnosis of metastatic
      melanoma have not been identified. To explore potential regulatory targets, we
      have analyzed the gene microarray expression profiles of malignant melanoma
      samples by co-expression analysis based on the network approach. The
      differentially expressed genes (DEGs) were screened by the EdgeR package of R
      software. A weighted gene co-expression network analysis (WGCNA) was used for the
      identification of DEGs in the special gene modules and hub genes. Subsequently, a
      protein-protein interaction network was constructed to extract hub genes
      associated with gene modules. Finally, twenty-four important hub genes (RASGRP2,
      IKZF1, CXCR5, LTB, BLK, LINGO3, CCR6, P2RY10, RHOH, JUP, KRT14, PLA2G3, SPRR1A,
      KRT78, SFN, CLDN4, IL1RN, PKP3, CBLC, KRT16, TMEM79, KLK8, LYPD3 and LYPD5) were
      treated as valuable factors involved in the immune response and tumor cell
      development in tumorigenesis. In addition, a transcriptional regulatory network
      was constructed for these specific modules or hub genes, and a few core
      transcriptional regulators were found to be mostly associated with our hub genes,
      including GATA1, STAT1, SP1, and PSG1. In summary, our findings enhance our
      understanding of the biological process of malignant melanoma metastasis,
      enabling us to identify specific genes to use for diagnostic and prognostic
      markers and possibly for targeted therapy.

PMID- 29377893
TI  - Improvement in cardiac dysfunction with a novel circuit training method combining
      simultaneous aerobic-resistance exercises. A randomized trial.
AB  - INTRODUCTION: Exercise is considered a valuable nonpharmacological intervention
      modality in cardiac rehabilitation (CR) programs in patients with ischemic heart
      disease. The effect of aerobic interval exercise combined with alternating sets
      of resistance training (super-circuit training, SCT) on cardiac patients' with
      reduced left ventricular function, post-myocardial infarction (MI) has not been
      thoroughly investigated. AIM OF STUDY: to improve cardiac function with a novel
      method of combined aerobic-resistance circuit training in a randomized control
      trial by way of comparing the effectiveness of continuous aerobic training (CAT)
      to SCT on mechanical cardiac function. Secondary to compare their effect on
      aerobic fitness, manual strength, and quality of life in men post MI. Finally, to
      evaluate the safety and feasibility of SCT. METHODS: 29 men post-MI participants
      were randomly assigned to either 12-weeks of CAT (n = 15) or SCT (n = 14). Both
      groups, CAT and SCT exercised at 60%-70% and 75-85% of their heart rate reserve,
      respectively. The SCT group also engaged in intermittently combined resistance
      training. Primary outcome measure was echocardiography. Secondary outcome
      measures were aerobic fitness, strength, and quality of life (QoL). The
      effectiveness of the two training programs was examined via paired t-tests and
      Cohen's d effect size (ES). RESULTS: Post-training, only the SCT group presented
      significant changes in echocardiography (a reduction in E/e' and an increase in
      ejection fraction, P<0.05). Similarly, only the SCT group presented significant
      changes in aerobic fitness (an increase in maximal metabolic equivalent, P<0.05).
      In addition, SCT improvement in the physical component of QoL was greater than
      this observed in the CAT group. In both training programs, no adverse events were
      observed. CONCLUSION: Men post-MI stand to benefit from both CAT and SCT.
      However, in comparison to CAT, as assessed by echocardiography, SCT may yield
      greater benefits to the left ventricle mechanical function as well as to the
      patient's aerobic fitness and physical QoL. Moreover, the SCT program was found
      to be feasible as well as safe.

PMID- 29377894
TI  - The extent of ribosome queuing in budding yeast.
AB  - Ribosome queuing is a fundamental phenomenon suggested to be related to topics
      such as genome evolution, synthetic biology, gene expression regulation,
      intracellular biophysics, and more. However, this phenomenon hasn't been
      quantified yet at a genomic level. Nevertheless, methodologies for studying
      translation (e.g. ribosome footprints) are usually calibrated to capture only
      single ribosome protected footprints (mRPFs) and thus limited in their ability to
      detect ribosome queuing. On the other hand, most of the models in the field
      assume and analyze a certain level of queuing. Here we present an experimental
      computational approach for studying ribosome queuing based on sequencing of RNA
      footprints extracted from pairs of ribosomes (dRPFs) using a modified ribosome
      profiling protocol. We combine our approach with traditional ribosome profiling
      to generate a detailed profile of ribosome traffic. The data are analyzed using
      computational models of translation dynamics. The approach was implemented on the
      Saccharomyces cerevisiae transcriptome. Our data shows that ribosome queuing is
      more frequent than previously thought: the measured ratio of ribosomes within
      dRPFs to mRPFs is 0.2-0.35, suggesting that at least one to five translating
      ribosomes is in a traffic jam; these queued ribosomes cannot be captured by
      traditional methods. We found that specific regions are enriched with queued
      ribosomes, such as the 5'-end of ORFs, and regions upstream to mRPF peaks, among
      others. While queuing is related to higher density of ribosomes on the transcript
      (characteristic of highly translated genes), we report cases where traffic jams
      are relatively more severe in lowly expressed genes and possibly even selected
      for. In addition, our analysis demonstrates that higher adaptation of the coding
      region to the intracellular tRNA levels is associated with lower queuing levels.
      Our analysis also suggests that the Saccharomyces cerevisiae transcriptome
      undergoes selection for eliminating traffic jams. Thus, our proposed approach is
      an essential tool for high resolution analysis of ribosome traffic during mRNA
      translation and understanding its evolution.

PMID- 29377895
TI  - The non-classical nuclear import carrier Transportin 1 modulates circadian
      rhythms through its effect on PER1 nuclear localization.
AB  - Circadian clocks are molecular timekeeping mechanisms that allow organisms to
      anticipate daily changes in their environment. The fundamental cellular basis of
      these clocks is delayed negative feedback gene regulation with PERIOD and
      CRYPTOCHROME containing protein complexes as main inhibitory elements. For a
      correct circadian period, it is essential that such clock protein complexes
      accumulate in the nucleus in a precisely timed manner, a mechanism that is poorly
      understood. We performed a systematic RNAi-mediated screen in human cells and
      identified 15 genes associated with the nucleo-cytoplasmic translocation
      machinery, whose expression is important for circadian clock dynamics. Among them
      was Transportin 1 (TNPO1), a non-classical nuclear import carrier, whose
      knockdown and knockout led to short circadian periods. TNPO1 was found in
      endogenous clock protein complexes and particularly binds to PER1 regulating its
      (but not PER2's) nuclear localization. While PER1 is also transported to the
      nucleus by the classical, Importin beta-mediated pathway, TNPO1 depletion slowed
      down PER1 nuclear import rate as revealed by fluorescence recovery after
      photobleaching (FRAP) experiments. In addition, we found that TNPO1-mediated
      nuclear import may constitute a novel input pathway of how cellular redox state
      signals to the clock, since redox stress increases binding of TNPO1 to PER1 and
      decreases its nuclear localization. Together, our RNAi screen knocking down
      import carriers (but also export carriers) results in short and long circadian
      periods indicating that the regulatory pathways that control the timing of clock
      protein subcellular localization are far more complex than previously assumed.
      TNPO1 is one of the novel players essential for normal circadian periods and
      potentially for redox regulation of the clock.

PMID- 29377897
TI  - The Camden & Islington Research Database: Using electronic mental health records
      for research.
AB  - BACKGROUND: Electronic health records (EHRs) are widely used in mental health
      services. Case registers using EHRs from secondary mental healthcare have the
      potential to deliver large-scale projects evaluating mental health outcomes in
      real-world clinical populations. METHODS: We describe the Camden and Islington
      NHS Foundation Trust (C&I) Research Database which uses the Clinical Record
      Interactive Search (CRIS) tool to extract and de-identify routinely collected
      clinical information from a large UK provider of secondary mental healthcare, and
      demonstrate its capabilities to answer a clinical research question regarding
      time to diagnosis and treatment of bipolar disorder. RESULTS: The C&I Research
      Database contains records from 108,168 mental health patients, of which 23,538
      were receiving active care. The characteristics of the patient population are
      compared to those of the catchment area, of London, and of England as a whole.
      The median time to diagnosis of bipolar disorder was 76 days (interquartile
      range: 17-391) and median time to treatment was 37 days (interquartile range: 5
      194). Compulsory admission under the UK Mental Health Act was associated with
      shorter intervals to diagnosis and treatment. Prior diagnoses of other
      psychiatric disorders were associated with longer intervals to diagnosis, though
      prior diagnoses of schizophrenia and related disorders were associated with
      decreased time to treatment. CONCLUSIONS: The CRIS tool, developed by the South
      London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC),
      functioned very well at C&I. It is reassuring that data from different
      organizations deliver similar results, and that applications developed in one
      Trust can then be successfully deployed in another. The information can be
      retrieved in a quicker and more efficient fashion than more traditional methods
      of health research. The findings support the secondary use of EHRs for large
      scale mental health research in naturalistic samples and settings investigated
      across large, diverse geographical areas.

PMID- 29377896
TI  - Identifying and exploiting trait-relevant tissues with multiple functional
      annotations in genome-wide association studies.
AB  - Genome-wide association studies (GWASs) have identified many disease associated
      loci, the majority of which have unknown biological functions. Understanding the
      mechanism underlying trait associations requires identifying trait-relevant
      tissues and investigating associations in a trait-specific fashion. Here, we
      extend the widely used linear mixed model to incorporate multiple SNP functional
      annotations from omics studies with GWAS summary statistics to facilitate the
      identification of trait-relevant tissues, with which to further construct
      powerful association tests. Specifically, we rely on a generalized estimating
      equation based algorithm for parameter inference, a mixture modeling framework
      for trait-tissue relevance classification, and a weighted sequence kernel
      association test constructed based on the identified trait-relevant tissues for
      powerful association analysis. We refer to our analytic procedure as the Scalable
      Multiple Annotation integration for trait-Relevant Tissue identification and
      usage (SMART). With extensive simulations, we show how our method can make use of
      multiple complementary annotations to improve the accuracy for identifying trait
      relevant tissues. In addition, our procedure allows us to make use of the
      inferred trait-relevant tissues, for the first time, to construct more powerful
      SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28
      GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and
      Roadmap. Our results reveal new trait-tissue relevance, pinpoint important
      annotations that are informative of trait-tissue relationship, and illustrate how
      we can use the inferred trait-relevant tissues to construct more powerful
      association tests in the Wellcome trust case control consortium study.

PMID- 29377898
TI  - Trypanosoma cruzi vaccine candidate antigens Tc24 and TSA-1 recall memory immune
      response associated with HLA-A and -B supertypes in Chagasic chronic patients
      from Mexico.
AB  - Trypanosoma cruzi antigens TSA-1 and Tc24 have shown promise as vaccine
      candidates in animal studies. We evaluated here the recall immune response these
      antigens induce in Chagasic patients, as a first step to test their
      immunogenicity in humans. We evaluated the in vitro cellular immune response
      after stimulation with recombinant TSA-1 (rTSA-1) or recombinant Tc24 (rTc24) in
      mononuclear cells of asymptomatic Chagasic chronic patients (n = 20) compared to
      healthy volunteers (n = 19) from Yucatan, Mexico. Proliferation assays,
      intracellular cytokine staining, cytometric bead arrays, and memory T cell
      immunophenotyping were performed by flow cytometry. Peripheral blood mononuclear
      cells (PBMC) from Chagasic patients showed significant proliferation after
      stimulation with rTc24 and presented a phenotype of T effector memory cells
      (CD45RA-CCR7-). These cells also produced IFN-gamma and, to a lesser extent IL10,
      after stimulation with rTSA-1 and rTc24 proteins. Overall, both antigens recalled
      a broad immune response in some Chagasic patients, confirming that their immune
      system had been primed against these antigens during natural infection. Analysis
      of HLA-A and HLA-B allele diversity by PCR-sequencing indicated that HLA-A03 and
      HLA-B07 were the most frequent supertypes in this Mexican population. Also, there
      was a significant difference in the frequency of HLA-A01 and HLA-A02 supertypes
      between Chagasic patients and controls, while the other alleles were evenly
      distributed. Some aspects of the immune response, such as antigen-induced IFN
      gamma production by CD4+ and CD8+ T cells and CD8+ proliferation, showed
      significant association with specific HLA-A supertypes, depending on the antigen
      considered. In conclusion, our results confirm the ability of both TSA-1 and Tc24
      recombinant proteins to recall an immune response induced by the native antigens
      during natural infection in at least some patients. Our data support the further
      development of these antigens as therapeutic vaccine against Chagas disease.

PMID- 29377899
TI  - A parsimonious characterization of change in global age-specific and total
      fertility rates.
AB  - This study aims to understand trends in global fertility from 1950-2010 though
      the analysis of age-specific fertility rates. This approach incorporates both the
      overall level, as when the total fertility rate is modeled, and different
      patterns of age-specific fertility to examine the relationship between changes in
      age-specific fertility and fertility decline. Singular value decomposition is
      used to capture the variation in age-specific fertility curves while reducing the
      number of dimensions, allowing curves to be described nearly fully with three
      parameters. Regional patterns and trends over time are evident in parameter
      values, suggesting this method provides a useful tool for considering fertility
      decline globally. The second and third parameters were analyzed using model-based
      clustering to examine patterns of age-specific fertility over time and place;
      four clusters were obtained. A country's demographic transition can be traced
      through time by membership in the different clusters, and regional patterns in
      the trajectories through time and with fertility decline are identified.

PMID- 29377900
TI  - Rewired RNAi-mediated genome surveillance in house dust mites.
AB  - House dust mites are common pests with an unusual evolutionary history, being
      descendants of a parasitic ancestor. Transition to parasitism is frequently
      accompanied by genome rearrangements, possibly to accommodate the genetic change
      needed to access new ecology. Transposable element (TE) activity is a source of
      genomic instability that can trigger large-scale genomic alterations. Eukaryotes
      have multiple transposon control mechanisms, one of which is RNA interference
      (RNAi). Investigation of the dust mite genome failed to identify a major RNAi
      pathway: the Piwi-associated RNA (piRNA) pathway, which has been replaced by a
      novel small-interfering RNA (siRNA)-like pathway. Co-opting of piRNA function by
      dust mite siRNAs is extensive, including establishment of TE control master loci
      that produce siRNAs. Interestingly, other members of the Acari have piRNAs
      indicating loss of this mechanism in dust mites is a recent event. Flux of RNAi
      mediated control of TEs highlights the unusual arc of dust mite evolution.

PMID- 29377901
TI  - Long-term effects of pancreas transplant alone on nephropathy in type 1 diabetic
      patients with optimal renal function.
AB  - BACKGROUND: Limited data are available regarding optimal selection criteria for
      pancreas transplant alone (PTA) to minimize aggravation of diabetic nephropathy.
      METHODS: A total of 87 type 1 diabetic patients were evaluated before and after
      PTA at a single center from January, 1999 to December, 2015, together with 87
      matched non-transplanted type 1 diabetic subjects who were candidates for PTA to
      compare deterioration of native kidney function. A total of 163 patients (79 in
      the transplanted group and 84 in the nontransplanted group) were finally enrolled
      after excluding nine patients with estimated glomerular filtration rate less than
      60 mL/min/1.73 m2 and two patients with moderate proteinuria (>= 1.5 g/day).
      RESULTS: A total of seven recipients (8.9%) had end-stage renal disease post
      transplant whereas only one patient (1.2%) developed end-stage renal disease in
      the nontransplanted group during their follow-up period (median 12.0, range 6-96
      months) (p = 0.03). Furthermore, a composite of severe renal dysfunction and end
      stage renal disease (31.6% vs 2.4%) was significantly higher in the transplanted
      group (p < 0.001). Multivariate Cox regression analysis revealed that a higher
      level of tacrolimus at six months post-transplant (HR = 1.648, CI = 1.140-2.385,
      p = 0.008) was the only significant factor associated with end-stage renal
      disease. CONCLUSIONS: There is a considerable risk for deterioration of renal
      function in PTA recipients post-transplant compared with non-transplant diabetic
      patients. With rather strict selection criteria such as preoperative proteinuria
      and estimated glomerular filtration rate, PTA should be considered in diabetic
      patients to minimize post-transplant aggravation of diabetic nephropathy.

PMID- 29377902
TI  - Reactome graph database: Efficient access to complex pathway data.
AB  - Reactome is a free, open-source, open-data, curated and peer-reviewed
      knowledgebase of biomolecular pathways. One of its main priorities is to provide
      easy and efficient access to its high quality curated data. At present,
      biological pathway databases typically store their contents in relational
      databases. This limits access efficiency because there are performance issues
      associated with queries traversing highly interconnected data. The same data in a
      graph database can be queried more efficiently. Here we present the rationale
      behind the adoption of a graph database (Neo4j) as well as the new ContentService
      (REST API) that provides access to these data. The Neo4j graph database and its
      query language, Cypher, provide efficient access to the complex Reactome data
      model, facilitating easy traversal and knowledge discovery. The adoption of this
      technology greatly improved query efficiency, reducing the average query time by
      93%. The web service built on top of the graph database provides programmatic
      access to Reactome data by object oriented queries, but also supports more
      complex queries that take advantage of the new underlying graph-based data
      storage. By adopting graph database technology we are providing a high
      performance pathway data resource to the community. The Reactome graph database
      use case shows the power of NoSQL database engines for complex biological data
      types.

PMID- 29377903
TI  - Cytomegalovirus induces HLA-class-II-restricted alloreactivity in an acute
      myeloid leukemia cell line.
AB  - Cytomegalovirus (HCMV) reactivation is found frequently after allogeneic
      hematopoietic stem cell transplantation (alloSCT) and is associated with an
      increased treatment-related mortality. Recent reports suggest a link between HCMV
      and a reduced risk of cancer progression in patients with acute leukemia or
      lymphoma after alloSCT. Here we show that HCMV can inhibit the proliferation of
      the acute myeloid leukemia cell line Kasumi-1 and the promyeloid leukemia cell
      line NB4. HCMV induced a significant up-regulation of HLA-class-II-molecules,
      especially HLA-DR expression and an increase of apoptosis, granzyme B, perforin
      and IFN-gamma secretion in Kasumi-1 cells cocultured with peripheral blood
      mononuclear cells (PBMCs). Indolamin-2,3-dioxygenase on the other hand led only
      to a significant dose-dependent effect on IFN-gamma secretion without effects on
      proliferation. The addition of CpG-rich oligonucleotides and ganciclovir reversed
      those antiproliferative effects. We conclude that HCMV can enhance alloreactivity
      of PBMCs against Kasumi-1 and NB4 cells in vitro. To determine if this phenomenon
      may be clinically relevant further investigations will be required.

PMID- 29377904
TI  - Analysis of channel uncertainty in ARQ relay networks.
AB  - Several power allocation algorithms for cooperative relay networks are presented
      in the literature. These contributions assume perfect channel knowledge and
      capacity achieving codes. However in practice, obtaining the channel state
      information at a relay or at the destination is an estimation problem and can
      generally not be error free. The investigation of the power allocation mechanism
      in a wireless network due to channel imperfections is important because it can
      severely degrade its performance regarding throughput and bit error rate. In this
      paper, the impact of imperfect channel state information on the power allocation
      of an adaptive relay network is investigated. Moreover, a framework including
      Automatic Repeat reQuest (ARQ) mechanism is provided to make the power allocation
      mechanism robust against these channel imperfections. For this framework, the end
      to-end SNR is calculated considering imperfect channel knowledge using ARQ
      analytically. The goal is to emphasize the impact of imperfect channel knowledge
      on the power allocation mechanism. In this paper, the simulation results
      illustrate the impact of channel uncertainties on the average outage probability,
      throughput, and consumed sum power for different qualities of channel estimation.
      It is shown that the presented framework with ARQ is extremely robust against the
      channel imperfections.

PMID- 29377905
TI  - 16S rRNA gene metabarcoding and TEM reveals different ecological strategies
      within the genus Neogloboquadrina (planktonic foraminifer).
AB  - Uncovering the complexities of trophic and metabolic interactions among
      microorganisms is essential for the understanding of marine biogeochemical
      cycling and modelling climate-driven ecosystem shifts. High-throughput DNA
      sequencing methods provide valuable tools for examining these complex
      interactions, although this remains challenging, as many microorganisms are
      difficult to isolate, identify and culture. We use two species of planktonic
      foraminifera from the climatically susceptible, palaeoceanographically important
      genus Neogloboquadrina, as ideal test microorganisms for the application of 16S
      rRNA gene metabarcoding. Neogloboquadrina dutertrei and Neogloboquadrina incompta
      were collected from the California Current and subjected to either 16S rRNA gene
      metabarcoding, fluorescence microscopy, or transmission electron microscopy (TEM)
      to investigate their species-specific trophic interactions and potential
      symbiotic associations. 53-99% of 16S rRNA gene sequences recovered from two
      specimens of N. dutertrei were assigned to a single operational taxonomic unit
      (OTU) from a chloroplast of the phylum Stramenopile. TEM observations confirmed
      the presence of numerous intact coccoid algae within the host cell, consistent
      with algal symbionts. Based on sequence data and observed ultrastructure, we
      taxonomically assign the putative algal symbionts to Pelagophyceae and not
      Chrysophyceae, as previously reported in this species. In addition, our data
      shows that N. dutertrei feeds on protists within particulate organic matter
      (POM), but not on bacteria as a major food source. In total contrast, of OTUs
      recovered from three N. incompta specimens, 83-95% were assigned to bacterial
      classes Alteromonadales and Vibrionales of the order Gammaproteobacteria. TEM
      demonstrates that these bacteria are a food source, not putative symbionts.
      Contrary to the current view that non-spinose foraminifera are predominantly
      herbivorous, neither N. dutertrei nor N. incompta contained significant numbers
      of phytoplankton OTUs. We present an alternative view of their trophic
      interactions and discuss these results within the context of modelling global
      planktonic foraminiferal abundances in response to high-latitude climate change.

PMID- 29377906
TI  - Enhanced susceptibility to stress and seizures in GAD65 deficient mice.
AB  - Reduced gamma-aminobutyric acid (GABA) inhibition has been implicated in both
      anxiety and epilepsy. GAD65-/- (NOD/LtJ) mice have significantly decreased basal
      GABA levels in the brain and a lowered threshold for seizure generation. One
      fifth of GAD65 -/- mice experienced stress-induced seizures upon exposure to an
      open field at 4 weeks of age. In each successive week until 8 weeks of age, the
      latency to seizures decreased with prior seizure experience. 100% of GAD65-/-
      mice exhibited stress-induced seizures by the end of 8 weeks. GAD65-/- mice also
      exhibited marked impairment in open field exploratory behavior and deficits in
      spatial learning acquisition on a Barnes maze. Anxiety-like behavior in an open
      field was observed prior to seizure onset and was predictive of subsequent
      seizures. Immunohistochemical characterization of interneuron subtypes in GAD65-/
      mice showed a selective decrease in GABA and neuropeptide Y (NPY) levels and no
      change in calbindin (CLB) or calretinin (CLR) immunoreactivity in the
      hippocampus. Stem cells from the medial ganglionic eminence (MGE) were injected
      into the hippocampal hilus to restore GABAergic interneurons. One week after
      transplantation, MGE-transplanted mice demonstrated significant seizure
      resistance compared to sham surgical controls. The percent area of GFP+ MGE graft
      in the hippocampus correlated significantly with the increase in seizure latency.
      Our data indicate that impaired GABAergic neurotransmission can cause anxiety
      like behavior and stress-induced seizures that can be rescued by MGE stem cell
      transplantation.

PMID- 29377907
TI  - ProtDataTherm: A database for thermostability analysis and engineering of
      proteins.
AB  - Protein thermostability engineering is a powerful tool to improve resistance of
      proteins against high temperatures and thereafter broaden their applications. For
      efficient protein thermostability engineering, different thermostability
      classified data sources including sequences and 3D structures are needed for
      different protein families. However, no data source is available providing such
      data easily. It is the first release of ProtDataTherm database for analysis and
      engineering of protein thermostability which contains more than 14 million
      protein sequences categorized based on their thermal stability and protein
      family. This database contains data needed for better understanding protein
      thermostability and stability engineering. Providing categorized protein
      sequences and structures as psychrophilic, mesophilic and thermophilic makes this
      database useful for the development of new tools in protein stability prediction.
      This database is available at http://profiles.bs.ipm.ir/softwares/protdatatherm.
      As a proof of concept, the thermostability that improves mutations were suggested
      for one sample protein belonging to one of protein families with more than 20
      mesophilic and thermophilic sequences and with known experimentally measured
      DeltaT of mutations available within ProTherm database.

PMID- 29377908
TI  - Spatio-temporal heterogeneity of malaria morbidity in Ghana: Analysis of routine
      health facility data.
AB  - BACKGROUND: Malaria incidence is largely influenced by vector abundance. Among
      the many interconnected factors relating to malaria transmission, weather
      conditions such as rainfall and temperature are known to create suitable
      environmental conditions that sustain reproduction and propagation of anopheles
      mosquitoes and malaria parasites. In Ghana, climatic conditions vary across the
      country. Understanding the heterogeneity of malaria morbidity using data sourced
      from a recently setup data repository for routine health facility data could
      support planning. METHODS: Monthly aggregated confirmed uncomplicated malaria
      cases from the District Health Information Management System and average monthly
      rainfall and temperature records obtained from the Ghana Meteorological Agency
      from 2008 to 2016 were analysed. Univariate time series models were fitted to the
      malaria, rainfall and temperature data series. After pre-whitening the morbidity
      data, cross correlation analyses were performed. Subsequently, transfer function
      models were developed for the relationship between malaria morbidity and rainfall
      and temperature. RESULTS: Malaria morbidity patterns vary across zones. In the
      Guinea savannah, morbidity peaks once in the year and twice in both the
      Transitional forest and Coastal savannah, following similar patterns of rainfall
      at the zonal level. While the effects of rainfall on malaria morbidity are
      delayed by a month in the Guinea savannah and Transitional Forest zones those of
      temperature are delayed by two months in the Transitional forest zone. In the
      Coastal savannah however, incidence of malaria is significantly associated with
      two months lead in rainfall and temperature. CONCLUSION: Data captured on the
      District Health Information Management System has been used to demonstrate
      heterogeneity in the dynamics of malaria morbidity across the country. Timing of
      these variations could guide the deployment of interventions such as indoor
      residual spraying, Seasonal Malaria Chemoprevention or vaccines to optimise
      effectiveness on zonal basis.

PMID- 29377909
TI  - Genomic analysis of head and neck cancer cases from two high incidence regions.
AB  - We investigated how somatic changes in HNSCC interact with environmental and host
      risk factors and whether they influence the risk of HNSCC occurrence and outcome.
      180-paired samples diagnosed as HNSCC in two high incidence regions of Europe and
      South America underwent targeted sequencing (14 genes) and evaluation of copy
      number alterations (SCNAs). TP53, PIK3CA, NOTCH1, TP63 and CDKN2A were the most
      frequently mutated genes. Cases were characterized by a low copy number burden
      with recurrent focal amplification in 11q13.3 and deletion in 15q22. Cases with
      low SCNAs showed an improved overall survival. We found significant correlations
      with decreased overall survival between focal amplified regions 4p16, 10q22 and
      22q11, and losses in 12p12, 15q14 and 15q22. The mutational landscape in our
      cases showed an association to both environmental exposures and clinical
      characteristics. We confirmed that somatic copy number alterations are an
      important predictor of HNSCC overall survival.

PMID- 29377910
TI  - The diagnostic performance of a novel ELISA for human CTP (Cochlin-tomoprotein)
      to detect perilymph leakage.
AB  - Perilymphatic fistula is defined as an abnormal communication between the
      perilymph-filled space and the middle ear, or cranial spaces. The manifestations
      include a broad spectrum of neuro-otological symptoms such as hearing loss,
      vertigo/dizziness, disequilibrium, aural fullness, tinnitus, and cognitive
      dysfunction. By sealing the fistula, perilymphatic fistula is a surgically
      correctable disease. Also, appropriate recognition and treatment of perilymphatic
      fistula can improve a patient's condition and hence the quality of life. However,
      the difficulty in making a definitive diagnosis due to the lack of an appropriate
      biomarker to detect perilymph leakage has caused a long-standing debate regarding
      its management. We have reported a clinical test for the diagnosis of
      perilymphatic fistula by detecting a perilymph specific protein, Cochlin
      tomoprotein, as a diagnostic marker using a western blot. The aim of this study
      is to establish an ELISA-based human Cochlin-tomoprotein detection test and to
      evaluate its diagnostic accuracy in clinical subjects. The results of ELISA
      showed good dilution reproducibility. The mean concentration was 49.7+/-9.4 of 10
      perilymph samples. The ROC curve in differentiating the perilymph leakage
      condition from the normal middle ear was significant (P < 0.001) with an area
      under the curve (AUC) of 0.918 (95% CI 0.824-0.100). We defined the diagnostic
      criteria as follows: CTP<0.4 negative; 0.4?CTP<0.8 intermediate; 0.8?CTP(ng/ml)
      positive in the clinical usage of the hCTP ELISA, and sensitivity and specificity
      were 86.4% and 100%, respectively. We further tested the expression specificity
      of the Cochlin-tomoprotein by testing blood and CSF samples. The concentration
      was below the detection limit (0.2 ng/ml) in 38 of the 40 blood, and 14 of the 19
      CSF samples. We report the accuracy of this test for the diagnosis of
      perilymphatic fistula. Using ELISA, we can improve the throughput of the test.
      Furthermore, it is useful for a large-scale study to characterize the clinical
      picture and delineate the management of this medical condition.

PMID- 29377911
TI  - Hybrid two-stage active contour method with region and edge information for
      intensity inhomogeneous image segmentation.
AB  - This paper presents a novel two-stage image segmentation method using an edge
      scaled energy functional based on local and global information for intensity
      inhomogeneous image segmentation. In the first stage, we integrate global
      intensity term with a geodesic edge term, which produces a preliminary rough
      segmentation result. Thereafter, by taking final contour of the first stage as
      initial contour, we begin second stage segmentation process by integrating local
      intensity term with geodesic edge term to get final segmentation result. Due to
      the suitable initialization from the first stage, the second stage precisely
      achieves desirable segmentation result for inhomogeneous image segmentation. Two
      stage segmentation technique not only increases the accuracy but also eliminates
      the problem of initial contour existed in traditional local segmentation methods.
      The energy function of the proposed method uses both global and local terms
      incorporated with compacted geodesic edge term in an additive fashion which uses
      image gradient information to delineate obscured boundaries of objects inside an
      image. A Gaussian kernel is adapted for the regularization of the level set
      function and to avoid an expensive re-initialization. The experiments were
      carried out on synthetic and real images. Quantitative validations were performed
      on Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) 2015 and PH2 skin
      lesion database. The visual and quantitative comparisons will demonstrate the
      efficiency of the proposed method.

PMID- 29377912
TI  - Recellularization of rat liver: An in vitro model for assessing human drug
      metabolism and liver biology.
AB  - Liver-like organoids that recapitulate the complex functions of the whole liver
      by combining cells, scaffolds, and mechanical or chemical cues are becoming
      important models for studying liver biology and drug metabolism. The advantages
      of growing cells in three-dimensional constructs include enhanced cell-cell and
      cell-extracellular matrix interactions and preserved cellular phenotype
      including, prevention of de-differentiation. In the current study, biomimetic
      liver constructs were made via perfusion decellularization of rat liver, with the
      goal of maintaining the native composition and structure of the extracellular
      matrix. We optimized our decellularization process to produce liver scaffolds in
      which immunogenic residual DNA was removed but glycosaminoglycans were
      maintained. When the constructs were recellularized with rat or human liver
      cells, the cells remained viable, capable of proliferation, and functional for 28
      days. Specifically, the cells continued to express cytochrome P450 genes and
      maintained their ability to metabolize a model drug, midazolam. Microarray
      analysis showed an upregulation of genes involved in liver regeneration and
      fibrosis. In conclusion, these liver constructs have the potential to be used as
      test beds for studying liver biology and drug metabolism.

PMID- 29377913
TI  - Epidemiology characteristics of human coronaviruses in patients with respiratory
      infection symptoms and phylogenetic analysis of HCoV-OC43 during 2010-2015 in
      Guangzhou.
AB  - Human coronavirus (HCoV) is one of the most common causes of respiratory tract
      infection throughout the world. To investigate the epidemiological and genetic
      variation of HCoV in Guangzhou, south China, we collected totally 13048 throat
      and nasal swab specimens from adults and children with fever and acute upper
      respiratory infection symptoms in Gunazhou, south China between July 2010 and
      June 2015, and the epidemiological features of HCoV and its species were studied.
      Specimens were screened for HCoV by real-time RT-PCR, and 7 other common
      respiratory viruses were tested simultaneously by PCR or real-time PCR. HCoV was
      detected in 294 cases (2.25%) of the 13048 samples, with most of them inpatients
      (251 cases, 85.4% of HCoV positive cases) and young children not in nursery
      (53.06%, 156 out of 294 HCoV positive cases). Four HCoVs, as OC43, 229E, NL63 and
      HKU1 were detected prevalent during 2010-2015 in Guangzhou, and among the HCoV
      positive cases, 60.20% were OC43, 16.67% were 229E, 14.97% were NL63 and 7.82%
      were HKU1. The month distribution showed that totally HCoV was prevalent in
      winter, but differences existed in different species. The 5 year distribution of
      HCoV showed a peak-valley distribution trend, with the detection rate higher in
      2011 and 2013 whereas lower in 2010, 2012 and 2014. The age distribution revealed
      that children (especially those <3 years old) and old people (>50 years) were
      both high risk groups to be infected by HCoV. Of the 294 HCoV positive patients,
      34.69% (101 cases) were co-infected by other common respiratory viruses, and
      influenza virus was the most common co-infecting virus (30/101, 29.70%). Fifteen
      HCoV-OC43 positive samples of 2013-2014 were selected for S gene sequencing and
      phylogenetic analysis, and the results showed that the 15 strains could be
      divided into 2 clusters in the phylogenetic tree, 12 strains of which formed a
      separate cluster that was closer to genotype G found in Malaysia. It was revealed
      for the first time that genotype B and genotype G of HCoV-OC43 co-circulated and
      the newly defined genotype G was epidemic as a dominant genotype during 2013-2014
      in Guanzhou, south China.

PMID- 29377914
TI  - Exploring the behaviour of water in glycerol solutions by using delayed
      luminescence.
AB  - The crucial role of water in the engine of life have encouraged many researchers
      in studying, both theoretically and experimentally, the possible "structure" of
      water. Many properties of water have been related to the interplay between two
      distinct and interconverting structural species, namely the low-density water
      (LDW) and the high-density water (HDW). Supported by the results obtained with
      other aqueous solutions, this paper deals with the possibility of using the ultra
      weak delayed luminescence (DL) to investigate water structuring in a mixture with
      glycerol, characterized only by hydrogen bonds between the various molecules.
      Spectral and temporal characteristics of DL decays give information on the two
      components of the mixture, by evidencing the contribution of water at glycerol
      concentrations close to the values used in cryopreservation. DL results have
      shown a correlation with LDW clusters size as determined by other researchers on
      the basis of neutron diffraction experiments and computational modelling, as
      reported in Literature.

PMID- 29377915
TI  - Highly multiplexed single-cell quantitative PCR.
AB  - We present a microfluidic device for rapid gene expression profiling in single
      cells using multiplexed quantitative polymerase chain reaction (qPCR). This
      device integrates all processing steps, including cell isolation and lysis,
      complementary DNA synthesis, pre-amplification, sample splitting, and measurement
      in twenty separate qPCR reactions. Each of these steps is performed in parallel
      on up to 200 single cells per run. Experiments performed on dilutions of purified
      RNA establish assay linearity over a dynamic range of at least 104, a qPCR
      precision of 15%, and detection sensitivity down to a single cDNA molecule. We
      demonstrate the application of our device for rapid profiling of microRNA
      expression in single cells. Measurements performed on a panel of twenty miRNAs in
      two types of cells revealed clear cell-to-cell heterogeneity, with evidence of
      spontaneous differentiation manifested as distinct expression signatures. Highly
      multiplexed microfluidic RT-qPCR fills a gap in current capabilities for single
      cell analysis, providing a rapid and cost-effective approach for profiling panels
      of marker genes, thereby complementing single-cell genomics methods that are best
      suited for global analysis and discovery. We expect this approach to enable new
      studies requiring fast, cost-effective, and precise measurements across hundreds
      of single cells.

PMID- 29377916
TI  - Vaccination potential of B and T epitope-enriched NP and M2 against Influenza A
      viruses from different clades and hosts.
AB  - To avoid outbreaks of influenza virus epidemics and pandemics among human
      populations, modern medicine requires the development of new universal vaccines
      that are able to provide protection from a wide range of influenza A virus
      strains. In the course of development of a universal vaccine, it is necessary to
      consider that immunity must be generated even against viruses from different
      hosts because new human epidemic virus strains have their origins in viruses of
      birds and other animals. We have enriched conserved viral proteins-nucleoprotein
      (NP) and matrix protein 2 (M2)-by B and T-cell epitopes not only human origin but
      also swine and avian origin. For this purpose, we analyzed M2 and NP sequences
      with respect to changes in the sequences of known T and B-cell epitopes and chose
      conserved and evolutionarily significant epitopes. Eventually, we found consensus
      sequences of M2 and NP that have the maximum quantity of epitopes that are 100%
      coincident with them. Consensus epitope-enriched amino acid sequences of M2 and
      NP proteins were included in a recombinant adenoviral vector. Immunization with
      Ad5-tet-M2NP induced strong CD8 and CD4 T cells responses, specific to each of
      the encoded antigens, i.e. M2 and NP. Eight months after immunization with Ad5
      tet-M2NP, high numbers of M2- and NP-responding "effector memory" CD44posCD62neg
      T cells were found in the mouse spleens, which revealed a long-term T cell immune
      memory conferred by the immunization. In all, the challenge experiments showed an
      extraordinarily wide-ranging efficacy of protection by the Ad5-tet-M2NP vaccine,
      covering 5 different heterosubtypes of influenza A virus (2 human, 2 avian and 1
      swine).

PMID- 29377917
TI  - Study of formation of green eggshell color in ducks through global gene
      expression.
AB  - The green eggshell color produced by ducks is a threshold trait that can be
      influenced by various factors, such as hereditary, environment and nutrition. The
      aim of this study was to investigate the genetic regulation of the formation of
      eggs with green shells in Youxian ducks. We performed integrative analysis of
      mRNAs and miRNAs expression profiling in the shell gland samples from ducks by
      RNA-Seq. We found 124 differentially expressed genes that were associated with
      various pathways, such as the ATP-binding cassette (ABC) transporter and solute
      carrier supper family pathways. A total of 31 differentially expressed miRNAs
      were found between ducks laying green eggs and white eggs. KEGG pathway analysis
      of the predicted miRNA target genes also indicated the functional characteristics
      of these miRNAs; they were involved in the ABC transporter pathway and the solute
      carrier (SLC) supper family. Analysis with qRT-PCR was applied to validate the
      results of global gene expression, which showed a correlation between results
      obtained by RNA-seq and RT-qPCR. Moreover, a miRNA-mRNA interaction network was
      established using correlation analysis of differentially expressed mRNA and
      miRNA. Compared to ducks that lay white eggs, ducks that lay green eggs include
      six up-regulated miRNAs that had regulatory effects on 35 down-regulated genes,
      and seven down-regulated miRNAs which influenced 46 up-regulated genes. For
      example, the ABC transporter pathway could be regulated by expressing gga-miR-144
      3p (up-regulated) with ABCG2 (up-regulated) and other miRNAs and genes. This
      study provides valuable information about mRNA and miRNA regulation in duck shell
      gland tissues, and provides foundational information for further study on the
      eggshell color formation and marker-assisted selection for Youxian duck breeding.

PMID- 29377918
TI  - Ecological suitability modeling for anthrax in the Kruger National Park, South
      Africa.
AB  - The spores of the soil-borne bacterium, Bacillus anthracis, which causes anthrax
      are highly resistant to adverse environmental conditions. Under ideal conditions,
      anthrax spores can survive for many years in the soil. Anthrax is known to be
      endemic in the northern part of Kruger National Park (KNP) in South Africa (SA),
      with occasional epidemics spreading southward. The aim of this study was to
      identify and map areas that are ecologically suitable for the harboring of B.
      anthracis spores within the KNP. Anthrax surveillance data and selected
      environmental variables were used as inputs to the maximum entropy (Maxent)
      species distribution modeling method. Anthrax positive carcasses from 1988-2011
      in KNP (n = 597) and a total of 40 environmental variables were used to predict
      and evaluate their relative contribution to suitability for anthrax occurrence in
      KNP. The environmental variables that contributed the most to the occurrence of
      anthrax were soil type, normalized difference vegetation index (NDVI) and
      precipitation. Apart from the endemic Pafuri region, several other areas within
      KNP were classified as ecologically suitable. The outputs of this study could
      guide future surveillance efforts to focus on predicted suitable areas for
      anthrax, since the KNP currently uses passive surveillance to detect anthrax
      outbreaks.

PMID- 29377919
TI  - Associations of recent weight loss with health care costs and utilization among
      older women.
AB  - The association of weight loss with health care costs among older women is
      uncertain. Our study aim was to examine the association of objectively measured
      weight change with subsequent total health care (THC) costs and other health care
      utilization among older women. Our study population included 2,083 women (mean
      age 80.2 years) enrolled in the Study of Osteoporotic Fractures and U.S. Medicare
      Fee for Service. Weight loss and gain were defined, respectively, as >=5%
      decrease and >=5% increase in body weight, and weight maintenance as <5% change
      in body weight over a period of 4.5 years. THC costs, outpatient costs,
      hospitalizations, and skilled nursing facility [SNF] utilization were estimated
      from Medicare claims for 1 year after the period during which weight change was
      measured. The associations of weight change with THC and outpatient costs were
      estimated using generalized linear models with gamma variance and log link
      functions, and with hospitalizations and SNF utilization using logistic models.
      Adjusted for age and current body mass index (BMI), weight loss compared with
      weight maintenance was associated with a 35% increase in THC costs ($2148 [95%
      CI, 745 to 3552], 2014 U.S. dollars), a 15% increase in outpatient costs ($329
      [95% C.I. -1 to 660]), and odds ratios of 1.42 (95% CI, 1.14 to 1.76) for >=1
      hospital stay and 1.45 (95% CI, 1.03 to 2.03) for >=1 SNF stay. These
      associations did not vary by BMI category. After additional adjustment for multi
      morbidity and functional status, associations of weight loss with all four
      outcomes were no longer significant. In conclusion, >=5% weight loss among older
      women is not associated with increased THC and outpatient costs, hospitalization,
      and SNF utilization, irrespective of BMI category after accounting for multi
      morbidity and impaired functional status that accompany weight loss.

PMID- 29377920
TI  - Elasmobranch bycatch in the Italian Adriatic pelagic trawl fishery.
AB  - Elasmobranchs are among the most threatened long-lived marine species worldwide,
      and incidental capture is a major source of mortality. The northern central
      Adriatic Sea, though one of the most overfished basins of the Mediterranean Sea,
      supports a very valuable marine biodiversity, including elasmobranchs. This study
      assesses the impact of the northern central Adriatic pelagic trawl fishery on
      common smooth-hound (Mustelus mustelus), spiny dogfish (Squalus acanthias),
      common eagle ray (Myliobatis aquila), and pelagic stingray (Pteroplatytrygon
      violacea) by examining incidental catches recorded between 2006 and 2015. The
      distribution of bycatch events was evaluated using geo-referenced data.
      Generalized Linear Models were computed to standardize the catch of the four
      species and to predict the relative abundance of bycatch events. Data analysis
      shows that most bycatch events involving all four species occurred in the
      northern Adriatic Sea. The models predicted significant, distinct temporal
      patterns of standardized catches in line with previous investigations. Water
      depth, season, and fishing region were the best predictors to explain bycatch
      events. The present data suggest that the northern Adriatic may be an important
      nursery area for several elasmobranchs. They also highlight the urgent need for a
      better understanding of the interactions between elasmobranchs and fisheries to
      develop and apply suitable, ad hoc management measures.

PMID- 29377921
TI  - Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.
AB  - Restraint and cold stress increase both corticosterone and glycemia, which lead
      to oxidative damages in hepatic tissue. This study assessed the effect of royal
      jelly (RJ) supplementation on the corticosterone level, glycemia, plasma enzymes
      and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats
      were allocated into no-stress, stress, no-stress supplemented with RJ and stress
      supplemented with RJ groups. Initially, RJ (200mg/Kg) was administered for
      fourteen days and stressed groups were submitted to chronic stress from the
      seventh day. The results showed that RJ supplementation decreases corticosterone
      levels and improves glycemia control after stress induction. RJ supplementation
      also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total
      antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in
      the liver. Thus, RJ supplementation reestablished the corticosterone levels and
      the hepatic antioxidant system in stressed rats, indicating an adaptogenic and
      hepatoprotective potential of RJ.

PMID- 29377922
TI  - Assessing the impacts of total liquid ventilation on left ventricular diastolic
      function in a model of neonatal respiratory distress syndrome.
AB  - BACKGROUND: Filling the lung with dense liquid perfluorocarbons during total
      liquid ventilation (TLV) might compress the myocardium, a plausible explanation
      for the instability occasionally reported with this technique. Our objective is
      to assess the impacts of TLV on the cardiovascular system, particularly left
      ventricular diastolic function, in an ovine model of neonatal respiratory
      distress syndrome. METHOD: Eight newborns lambs, 3.0 +/- 0.4 days (3.2 +/- 0.3kg)
      were used in this crossover experimental study. Animals were intubated,
      anesthetized and paralyzed. Catheters were inserted in the femoral and pulmonary
      arteries. A high-fidelity pressure catheter was inserted into the left ventricle.
      Surfactant deficiency was induced by repeated lung lavages with normal saline.
      TLV was then conducted for 2 hours using a liquid ventilator prototype. Thoracic
      echocardiography and cardiac output assessment by thermodilution were performed
      before and during TLV. RESULTS: Left ventricular end diastolic pressure (LVEDP)
      (9.3 +/- 2.1 vs. 9.2 +/- 2.4mmHg, p = 0.89) and dimension (1.90 +/- 0.09 vs. 1.86
      +/- 0.12cm, p = 0.72), negative dP/dt (-2589 +/- 691 vs. -3115 +/- 866mmHg/s, p =
      0.50) and cardiac output (436 +/- 28 vs. 481 +/- 59ml/kg/min, p = 0.26) were not
      affected by TLV initiation. Left ventricular relaxation time constant (tau)
      slightly increased from 21.5 +/- 3.3 to 24.9 +/- 3.7ms (p = 0.03). Mean arterial
      systemic (48 +/- 6 vs. 53 +/- 7mmHg, p = 0.38) and pulmonary pressures (31.3 +/-
      2.5 vs. 30.4 +/- 2.3mmHg, p = 0.61) were stable. As expected, the inspiratory
      phase of liquid cycling exhibited a small but significant effect on most
      variables (i.e. central venous pressure +2.6 +/- 0.5mmHg, p = 0.001; LVEDP +1.18
      +/- 0.12mmHg, p<0.001). CONCLUSIONS: TLV was well tolerated in our neonatal lamb
      model of severe respiratory distress syndrome and had limited impact on left
      ventricle diastolic function when compared to conventional mechanical
      ventilation.

PMID- 29377923
TI  - Clinical prediction models for mortality and functional outcome following
      ischemic stroke: A systematic review and meta-analysis.
AB  - OBJECTIVE: We aim to identify and critically appraise clinical prediction models
      of mortality and function following ischaemic stroke. METHODS: Electronic
      databases, reference lists, citations were searched from inception to September
      2015. Studies were selected for inclusion, according to pre-specified criteria
      and critically appraised by independent, blinded reviewers. The discrimination of
      the prediction models was measured by the area under the curve receiver operating
      characteristic curve or c-statistic in random effects meta-analysis.
      Heterogeneity was measured using I2. Appropriate appraisal tools and reporting
      guidelines were used in this review. RESULTS: 31395 references were screened, of
      which 109 articles were included in the review. These articles described 66
      different predictive risk models. Appraisal identified poor methodological
      quality and a high risk of bias for most models. However, all models precede the
      development of reporting guidelines for prediction modelling studies.
      Generalisability of models could be improved, less than half of the included
      models have been externally validated(n = 27/66). 152 predictors of mortality and
      192 predictors and functional outcome were identified. No studies assessing
      ability to improve patient outcome (model impact studies) were identified.
      CONCLUSIONS: Further external validation and model impact studies to confirm the
      utility of existing models in supporting decision-making is required. Existing
      models have much potential. Those wishing to predict stroke outcome are advised
      to build on previous work, to update and adapt validated models to their specific
      contexts opposed to designing new ones.

PMID- 29377924
TI  - Adiposity cut-off points for cardiovascular disease and diabetes risk in the
      Portuguese population: The PORMETS study.
AB  - OBJECTIVES: The contribution of adiposity to cardiovascular and diabetes risk
      justifies the inclusion of an adiposity measure, usually waist circumference, in
      the definition of metabolic syndrome. However, waist circumference thresholds
      differ across populations. Our aim was to assess which adiposity measure performs
      the best in identifying the metabolic syndrome in a sample of Portuguese
      participants and to estimate cut-off values for these measures. METHODS: Data
      were obtained from a cross-sectional study (PORMETS study) conducted in Portugal
      between 2007 and 2009. A representative sample of non-institutionalized adults,
      comprising 3,956 participants, aged 18 years and older, was evaluated. A
      structured questionnaire was administered, collecting information on personal
      medical history, socio-demographics and behavioral characteristics.
      Anthropometrics, blood pressure and venous blood samples were also obtained.
      Metabolic syndrome was defined according to the Joint Interim Statement of the
      International Diabetes Federation Task Force on Epidemiology recommended
      criteria. Elevated cardiometabolic risk was considered when two or more of the
      four criteria of metabolic syndrome were present, excluding the waist
      circumference component. A receiver operating characteristic curve was used to
      estimate cut-off points. RESULTS: This study found that waist-to-height ratio,
      waist circumference and body adiposity index performed better than other
      adiposity measures, such as body mass index. The estimated cut-off points for
      waist-to-height ratio, waist circumference and body adiposity index in women and
      men were 0.564 / 89 cm / 27.4 and 0.571 / 93.5 cm / 25.5, respectively.
      CONCLUSION: As waist circumference is currently used as the adiposity measure in
      the definition of metabolic syndrome and as no relevant differences were observed
      between this measure and waist-to-height ratio, it is likely that no modification
      to the metabolic syndrome definition needs to be proposed. Moreover, this study
      also confirmed the applicability of European cut-off points in the Portuguese
      population.

PMID- 29377925
TI  - Individual differences in compliance and agreement for sleep logs and wrist
      actigraphy: A longitudinal study of naturalistic sleep in healthy adults.
AB  - There is extensive laboratory research studying the effects of acute sleep
      deprivation on biological and cognitive functions, yet much less is known about
      naturalistic patterns of sleep loss and the potential impact on daily or weekly
      functioning of an individual. Longitudinal studies are needed to advance our
      understanding of relationships between naturalistic sleep and fluctuations in
      human health and performance, but it is first necessary to understand the
      efficacy of current tools for long-term sleep monitoring. The present study used
      wrist actigraphy and sleep log diaries to obtain daily measurements of sleep from
      30 healthy adults for up to 16 consecutive weeks. We used non-parametric Bland
      Altman analysis and correlation coefficients to calculate agreement between
      subjectively and objectively measured variables including sleep onset time, sleep
      offset time, sleep onset latency, number of awakenings, the amount of wake time
      after sleep onset, and total sleep time. We also examined compliance data on the
      submission of daily sleep logs according to the experimental protocol. Overall,
      we found strong agreement for sleep onset and sleep offset times, but relatively
      poor agreement for variables related to wakefulness including sleep onset
      latency, awakenings, and wake after sleep onset. Compliance tended to decrease
      significantly over time according to a linear function, but there were
      substantial individual differences in overall compliance rates. There were also
      individual differences in agreement that could be explained, in part, by
      differences in compliance. Individuals who were consistently more compliant over
      time also tended to show the best agreement and lower scores on behavioral
      avoidance scale (BIS). Our results provide evidence for convergent validity in
      measuring sleep onset and sleep offset with wrist actigraphy and sleep logs, and
      we conclude by proposing an analysis method to mitigate the impact of non
      compliance and measurement errors when the two methods provide discrepant
      estimates.

PMID- 29377926
TI  - Impact of understory vegetation on soil carbon and nitrogen dynamic in aerially
      seeded Pinus massoniana plantations.
AB  - Understory vegetation plays a vital role in regulating soil carbon (C) and
      nitrogen (N) characteristics due to differences in plant functional traits.
      Different understory vegetation types have been reported following aerial
      seeding. While aerial seeding is common in areas with serious soil erosion, few
      studies have been conducted to investigate changes in soil C and N cycling as
      affected by understory vegetation in aerially seeded plantations. Here, we
      studied soil C and N characteristics under two naturally formed understory
      vegetation types (Dicranopteris and graminoid) in aerially seeded Pinus
      massoniana Lamb plantations. Across the two studied understory vegetation types,
      soil organic C was significantly correlated with all measured soil N variables,
      including total N, available N, microbial biomass N and water-soluble organic N,
      while microbial biomass C was correlated with all measured variables except soil
      organic C. Dicranopteris and graminoid differed in their effects on soil C and N
      process. Except water-soluble organic C, all the other C and N variables were
      higher in soils with graminoids. The higher levels of soil organic C, microbial
      biomass C, total N, available N, microbial biomass N and water-soluble organic N
      were consistent with the higher litter and root quality (C/N) of graminoid
      vegetation compared to Dicranopteris. Changes in soil C and N cycles might be
      impacted by understory vegetation types via differences in litter or root
      quality.

PMID- 29377927
TI  - Effect of body mass index on diabetogenesis factors at a fixed fasting plasma
      glucose level.
AB  - AIM: The present study evaluated the relative influence of body mass index (BMI)
      on insulin resistance (IR), first-phase insulin secretion (FPIS), second-phase
      insulin secretion (SPIS), and glucose effectiveness (GE) at a fixed fasting
      plasma glucose level in an older ethnic Chinese population. METHODS: In total,
      265 individuals aged 60 years with a fasting plasma glucose level of 5.56 mmol/L
      were enrolled. Participants had BMIs of 20.0-34.2 kg/m2. IR, FPIS, SPIS, and GE
      were estimated using our previously developed equations. Pearson correlation
      analysis was conducted to assess the correlations between the four diabetogenesis
      factors and BMI. A general linear model was used to determine the differences in
      the percentage of change among the four factor slopes against BMI. RESULTS:
      Significant correlations were observed between BMI and FPIS, SPIS, IR, and GE in
      both women and men, which were higher than those reported previously. In men, BMI
      had the most profound effect on SPIS, followed by IR, FPIS, and GE, whereas in
      women, the order was slightly different: IR, followed by FPIS, SPIS, and GE.
      Significant differences were observed among all these slopes, except for the
      slopes between FPIS and SPIS in women (p = 0.856) and IR and FPIS in men (p =
      0.258). CONCLUSIONS: The contribution of obesity to all diabetes factors, except
      GE, was higher than that reported previously. BMI had the most profound effect on
      insulin secretion in men and on IR in women in this 60-year-old cohort,
      suggesting that lifestyle modifications for obesity reduction in women remain the
      most important method for improving glucose metabolism and preventing future type
      2 diabetes mellitus.

PMID- 29377928
TI  - Effect of hyperbaric oxygen therapy (HBO) on implant-associated osteitis in a
      femur fracture model in mice.
AB  - Hyperbaric oxygen therapy (HBO) is applied very successfully in treatment of
      various diseases such as chronic wounds. It has been already suggested as
      adjunctive treatment option for osteitis by immune- and fracture modulating
      effects. This study evaluates the importance of HBO in an early implant
      associated localized osteitis caused by Staphylococcus aureus (SA) compared to
      the standard therapy. In a standardized murine model the left femur of 120 BALB/c
      mice were osteotomized and fixed by a titanium locking plate. Osteitis has been
      induced with a defined amount of SA into the fracture gap. Debridement and
      lavages were progressed on day 7, 14, 28 and 56 to determine the local bacterial
      growth and the immune reaction. Hyperbaric oxygen (2 ATA, 90%) was applied for 90
      minutes on day 7 to 21 for those mice allocated to HBO therapy. To evaluate the
      effect of HBO therapy the following groups were analyzed: Two sham-groups (12
      mice / group) with and without HBO therapy, two osteotomy groups (24 mice /
      group) with plate osteosynthesis of the femur with and without HBO therapy, and
      two osteotomy SA infection groups (24 mice / group) with and without HBO therapy.
      Fracture healing was also quantified on day 7, 14, 28 and 56 by a.p. x-ray and
      bone healing markers from blood samples. Progression of infection was assessed by
      estimation of colony-forming units (CFU) and immune response was analyzed by
      determination of polymorphonuclear neutrophils (PMN), Interleukin (IL) - 6, and
      the circulating free DNA (cfDNA) in lavage samples. Osteitis induced
      significantly higher IL-6, cfDNA- and PMN-levels in the lavage samples (on day 7
      and 14, each p < 0.05). HBO-therapy did not have a significant influence on the
      CFU and immune response compared to the standard therapy (each p > 0.05). At the
      same time HBO-therapy was associated with a delayed bone healing assessed by x
      ray radiography and a higher rate of non-union until day 28. In conclusion,
      osteitis led to significantly higher bacterial count and infection parameters.
      HBO-therapy neither had a beneficial influence on local infection nor on immune
      response or fracture healing compared to the standard therapy in an osteitis
      mouse model.

PMID- 29377929
TI  - CD73-A2a adenosine receptor axis promotes innate B cell antibody responses to
      pneumococcal polysaccharide vaccination.
AB  - Many individuals at risk of streptococcal infection respond poorly to the
      pneumococcal polysaccharide vaccine Pneumovax 23. Identification of actionable
      pathways able to enhance Pneumovax responsiveness is highly relevant. We
      investigated the contribution of the extracellular adenosine pathway regulated by
      the ecto-nucleotidase CD73 in Pneumovax-induced antibody responses. Using gene
      targeted mice, we demonstrated that CD73-or A2a adenosine receptor deficiency
      significantly delayed isotype switching. Nevertheless, CD73- or A2aR- deficient
      adult mice ultimately produced antigen-specific IgG3 and controlled Streptococcus
      pneumoniae infection as efficiently as wild type (WT) mice. Compared to adults,
      young WT mice failed to control S. pneumoniae infection after vaccination and
      this was associated with lower levels of CD73 on innate B cells. We hypothesized
      that pharmacological activation of A2a receptor may improve Pneumovax 23
      immunization in young WT mice. Remarkably, administration of the A2a adenosine
      receptor agonist CGS 21680 significantly increased IgG3 responses and
      significantly enhanced survival after S. pneumoniae challenge. Our study thus
      suggests that pharmacological activation of the A2a adenosine receptor could
      improve the efficacy of Pneumovax 23 vaccination in individuals at risk of
      streptococcal infection.

PMID- 29377930
TI  - Facebook as communication support for persons with potential mild acquired
      cognitive impairment: A content and social network analysis study.
AB  - INTRODUCTION: Social media has the potential to increase social participation and
      support for the well-being of individuals with chronic medical conditions. To
      date, Facebook is the most popular social medium for different types of
      communication. However, there is a lack of knowledge about the potential use of
      Facebook as a means of communication for persons with potential Mild Acquired
      Cognitive Impairment (MACI), a non-progressive mild cognitive impairment after an
      acquired brain injury. The aim of this study was to explore how persons with
      potential MACI, specifically persons with perceived brain fatigue after brain
      injury, communicate through Facebook, to classify the content of the
      communication and to visualize the frequency and types of interactions. METHODS
      AND MATERIALS: A social network analysis of the interactions between members' and
      a qualitative content analysis of a whole year's communication of a public
      Facebook group for Swedish speaking persons (1310 members) with perceived brain
      fatigue after an illness or injury to the brain were performed. RESULTS: The
      results showed how members use social media technology and Facebook as a means
      for communication and support for their condition. Individual group members
      showed very different patterns of communication and interactions. However, for
      the group as a whole, the most frequent topics in their communication were
      related to informational support and banter in posts, and socialization in
      comments. The findings also showed that the majority of members only communicated
      with few other members and had few direct communications. The most used
      communication feature of Facebook was likes in form of "thumbs-up". CONCLUSIONS:
      This study indicated that social media and in this case Facebook is used for
      communication and social support by persons with potential MACI, and revealed
      that their communication behavior is similar to the healthy population. Further
      studies relating specific cognitive problems of the participants to the use of
      social media would provide more reliable results for this specific group.

PMID- 29377932
TI  - Retraction: Dysferlin Interacts with Histone Deacetylase 6 and Increases alpha
      Tubulin Acetylation.

PMID- 29377931
TI  - Transcriptional regulatory control of mammalian nephron progenitors revealed by
      multi-factor cistromic analysis and genetic studies.
AB  - Nephron progenitor number determines nephron endowment; a reduced nephron count
      is linked to the onset of kidney disease. Several transcriptional regulators
      including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required
      for specification and/or maintenance of nephron progenitors. However, little is
      known about the regulatory intersection of these players. Here, we have mapped
      nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and
      Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes
      closely associated with progenitor programs. To examine their functional
      significance, we deleted 'hotspot' enhancer elements for Six2 and Wnt4. Removal
      of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression.
      When combined with a Six2 null allele, progeny display a premature depletion of
      nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of
      Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype
      also enhanced in combination with a Wnt4 null mutation. To explore the regulatory
      landscape that supports proper target gene expression, we performed CTCF ChIP-seq
      to identify insulator-boundary regions. One such putative boundary lies between
      the Six2 and Six3 loci. Evidence for the functional significance of this boundary
      was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant
      allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound
      boundary, removing Six2 from its distal enhancer regulation, but placed next to
      Six3 enhancer elements which support ectopic Six2 expression in the lens where
      Six3 is normally expressed. Six3 is now predicted to fall under control of the
      Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in
      nephron progenitors. 4C-seq supports the model for Six2 distal enhancer
      interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our
      view of the regulatory genome and regulatory landscape underpinning mammalian
      nephrogenesis.

PMID- 29377933
TI  - Tailor-made gene silencing of Staphylococcus aureus clinical isolates by CRISPR
      interference.
AB  - Preparing the genetically modified organisms have required much time and labor,
      making it the rate-limiting step but CRISPR/Cas9 technology appearance has
      changed this difficulty. Although reports on CRISPR/Cas9 technology such as
      genome editing and CRISPR interference (CRISPRi) in eukaryotes increased, those
      in prokaryotes especially in Staphylococci were limited. Thus, its potential in
      the bacteriology remains unexplored. This is attributed to ecological difference
      between eukaryotes and prokaryotes. Here, we constructed a novel CRISPRi plasmid
      vector, pBACi for Staphylococcus aureus. The transformation efficiency of S.
      aureus was ~104 CFU/MUg DNA using a vector extracted from dcm negative, which
      encoded one of DNA modification genes, E. coli. Further, pBACi was introduced
      into various clinical isolates including that not accepting the conventional
      temperature-sensitive vector. dcas9 in the vector was expressed throughout the
      growth phases of S. aureus and this vector decreased various gene mRNA
      expressions based on the crRNA targeting sequences and altered the knockdown
      strains' phenotypes. The targeted genes included various virulence and antibiotic
      resistant genes. Bioinformatics suggest this vector can be introduced into wide
      range of low-GC Gram-positive bacteria. Because this new CRISPR/Cas9-based vector
      can easily prepare knockdown strains, we believe the novel vector will facilitate
      the characterization of the function of genes from S. aureus and other Gram
      positive bacteria.

PMID- 29377935
TI  - Correction: Preference index supported by motivation tests in Nile tilapia.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0175821.].

PMID- 29377934
TI  - Vitamin A status in healthy women eating traditionally prepared spirulina (Dihe)
      in the Chad Lake area.
AB  - BACKGROUND: Chad Lake is a central place in a region with a high prevalence of
      vitamin A deficiency. Spirulina, a natural source of beta-carotene, is
      traditionally produced and eaten as "Dihe" around Chad Lake. beta-carotene
      spirulina has been found to have a high conversion factor to retinol. The aim of
      the study was to assess if the retinol status between healthy women eating
      spirulina Dihe daily (SPI+) and not (SPI-) in the Chad Lake area was different.
      METHODS: This study was observational: 88 healthy women were recruited and
      selected according to clinical criteria and their willingness to participate.
      They were divided in two groups according to their Dihe daily consumption: those
      who eat Dihe (SPI+; n = 35) and those who do not (SPI-; n = 35). After
      anthropometric and dietary assessments, blood retinol, beta-carotene, retinol
      binding, and inflammatory/nutritional proteins were measured. RESULTS: The diet
      between groups was identical, except for beta-carotene consumption, which was
      higher in SPI+ than in SPI- (10.8 vs. 1.8 mg/day). The serum retinol and beta
      carotene concentrations were significantly higher in SPI+ than in SPI- at 1.26 +/
      0.36 MUmol/l versus 1.03 +/- 0.31 MUmol/l (p = 0.008) and 0.59 +/-0.37 MUmol/l
      versus 0.46+/- 0.31 MUmol/l (p = 0.04), respectively. Seventy-seven percent of
      SPI+ versus 29% of SPI- had an adequate blood retinol value (p = 0.01).
      CONCLUSION: The results confirm that beta-carotene in spirulina is an effective
      positive modulator of blood retinol status. Dihe is a potential natural source of
      beta-carotene to achieve a proper vitamin A status in healthy women living near
      Chad Lake.

PMID- 29377936
TI  - Alphavirus-induced hyperactivation of PI3K/AKT directs pro-viral metabolic
      changes.
AB  - Virus reprogramming of cellular metabolism is recognised as a critical
      determinant for viral growth. While most viruses appear to activate central
      energy metabolism, different viruses have been shown to rely on alternative
      mechanisms of metabolic activation. Whether related viruses exploit conserved
      mechanisms and induce similar metabolic changes is currently unclear. In this
      work we investigate how two alphaviruses, Semliki Forest virus and Ross River
      virus, reprogram host metabolism and define the molecular mechanisms responsible.
      We demonstrate that in both cases the presence of a YXXM motif in the viral
      protein nsP3 is necessary for binding to the PI3K regulatory subunit p85 and for
      activating AKT. This leads to an increase in glucose metabolism towards the
      synthesis of fatty acids, although additional mechanisms of metabolic activation
      appear to be involved in Ross River virus infection. Importantly, a Ross River
      virus mutant that fails to activate AKT has an attenuated phenotype in vivo,
      suggesting that viral activation of PI3K/AKT contributes to virulence and
      disease.

PMID- 29377938
TI  - Correction: Palpation force modulation strategies to identify hard regions in
      soft tissue organs.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0171706.].

PMID- 29377937
TI  - The Xanthomonas euvesicatoria type III effector XopAU is an active protein kinase
      that manipulates plant MAP kinase signaling.
AB  - The Gram-negative bacterium Xanthomonas euvesicatoria (Xe) is the causal agent of
      bacterial spot disease of pepper and tomato. Xe delivers effector proteins into
      host cells through the type III secretion system to promote disease. Here, we
      show that the Xe effector XopAU, which is conserved in numerous Xanthomonas
      species, is a catalytically active protein kinase and contributes to the
      development of disease symptoms in pepper plants. Agrobacterium-mediated
      expression of XopAU in host and non-host plants activated typical defense
      responses, including MAP kinase phosphorylation, accumulation of pathogenesis
      related (PR) proteins and elicitation of cell death, that were dependent on the
      kinase activity of the effector. XopAU-mediated cell death was not dependent on
      early signaling components of effector-triggered immunity and was also observed
      when the effector was delivered into pepper leaves by Xanthomonas campestris pv.
      campestris, but not by Xe. Protein-protein interaction studies in yeast and in
      planta revealed that XopAU physically interacts with components of plant immunity
      associated MAP kinase cascades. Remarkably, XopAU directly phosphorylated MKK2 in
      vitro and enhanced its phosphorylation at multiple sites in planta. Consistent
      with the notion that MKK2 is a target of XopAU, silencing of the MKK2 homolog or
      overexpression of the catalytically inactive mutant MKK2K99R in N. benthamiana
      plants reduced XopAU-mediated cell death and MAPK phosphorylation. Furthermore,
      yeast co-expressing XopAU and MKK2 displayed reduced growth and this phenotype
      was dependent on the kinase activity of both proteins. Together, our results
      support the conclusion that XopAU contributes to Xe disease symptoms in pepper
      plants and manipulates host MAPK signaling through phosphorylation and activation
      of MKK2.

PMID- 29377939
TI  - Plasma concentration of selected biochemical markers of endothelial dysfunction
      in women with various severity of chronic venous insufficiency (CVI)-A pilot
      study.
AB  - BACKGROUND: Although the endothelial dysfunction is considered to be implicated
      in the pathogenesis of chronic venous insufficiency (CVI) the endothelial status
      in patients with venous disorders is still not fully evaluated. Therefore the aim
      of the study was to measure the concentration of selected markers of endothelial
      dysfunction: von Willebrand factor (vWf), soluble P-selectin (sP-selectin),
      soluble thrombomodulin (sTM) and soluble VE-cadherin (sVE-cadherin) in CVI women
      who constitute the most numerous group of patients suffering from venous disease.
      MATERIALS AND METHODS: Forty four women with CVI were involved in the study and
      divided into subgroups based on CEAP classification. Concentration of vWf, sP
      selectin, sTM and sVE-cadherin were measured and compared with those obtained in
      25 healthy age and sex-matched women. RESULTS: It was found that the
      concentration of sTM increased and sVEcadherin decreased along with disease
      severity in CVI women. A significant rise of sTM was observed especially in CVI
      women, with the highest inflammation status reflected by hsCRP or elastase
      concentration, and in CVI women with a high oxidative stress manifested by an
      increased plasma MDA. A significant fall of circulating sVE-cadherin was reported
      in CVI women with moderate to highest intensity of inflammation and oxidative
      stress. There was no change in vWF and sP-selectin concentration at any stage of
      CVI severity. CONCLUSIONS: The results of the present study demonstrate the
      presence of endothelial dysfunction in women suffering from CVI which seems to
      progress with the disease severity and may be associated with inflammation and
      enhanced oxidative stress.

PMID- 29377940
TI  - Global synonymous mutagenesis identifies cis-acting RNA elements that regulate
      HIV-1 splicing and replication.
AB  - The ~9.5 kilobase HIV-1 genome contains RNA sequences and structures that control
      many aspects of viral replication, including transcription, splicing, nuclear
      export, translation, packaging and reverse transcription. Nonetheless, chemical
      probing and other approaches suggest that the HIV-1 genome may contain many more
      RNA secondary structures of unknown importance and function. To determine whether
      there are additional, undiscovered cis-acting RNA elements in the HIV-1 genome
      that are important for viral replication, we undertook a global silent
      mutagenesis experiment. Sixteen mutant proviruses containing clusters of ~50 to
      ~200 synonymous mutations covering nearly the entire HIV-1 protein coding
      sequence were designed and synthesized. Analyses of these mutant viruses resulted
      in their division into three phenotypic groups. Group 1 mutants exhibited near
      wild-type replication, Group 2 mutants exhibited replication defects accompanied
      by perturbed RNA splicing, and Group 3 mutants had replication defects in the
      absence of obvious splicing perturbation. The three phenotypes were caused by
      mutations that exhibited a clear regional bias in their distribution along the
      viral genome, and those that caused replication defects all caused reductions in
      the level of unspliced RNA. We characterized in detail the underlying defects for
      Group 2 mutants. Second-site revertants that enabled viral replication could be
      derived for Group 2 mutants, and generally contained point mutations that reduced
      the utilization of proximal splice sites. Mapping of the changes responsible for
      splicing perturbations in Group 2 viruses revealed the presence of several RNA
      sequences that apparently suppressed the use of cryptic or canonical splice
      sites. Some sequences that affected splicing were diffusely distributed, while
      others could be mapped to discrete elements, proximal or distal to the affected
      splice site(s). Overall, our data indicate complex negative regulation of HIV-1
      splicing by RNA elements in various regions of the HIV-1 genome that enable
      balanced splicing and viral replication.

PMID- 29377942
TI  - Correction: Correlation between ICDAS and histology: Differences between
      stereomicroscopy and microradiography with contrast solution as histological
      techniques.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0183432.].

PMID- 29377941
TI  - Sex differences in the outcomes of stent implantation in mini-swine model.
AB  - Sex-related differences have been noted in cardiovascular anatomy,
      pathophysiology, and treatment responses, yet we continued to drive evaluation of
      vascular device development in animal models without consideration of animal sex.
      We aimed to understand sex-related differences in the vascular responses to stent
      implantation by analyzing the pooled data of endovascular interventions in 164
      Yucatan mini-swine (87 female, 77 male). Bare metal stents (BMS) or drug-eluting
      stents (DES) were implanted in 212 coronary arteries (63 single BMS implantation,
      68 single DES implantation, 33 overlapped BMS implantation, and 48 overlapped DES
      implantation). Histomorphological parameters were evaluated from vascular
      specimens at 3-365 days after stent implantation and evaluated values were
      compared between female and male groups. While neointima formation at all times
      after implantation was invariant to sex, statistically significant differences
      between female and male groups were observed in injury, inflammation, adventitial
      fibrosis, and neointimal fibrin deposition. These differences were observed
      independently, i.e., for different procedure types and at different follow-up
      timings. Only subtle temporal sex-related differences were observed in extent and
      timing of resolution of inflammation and fibrin clearance. These subtle sex
      related differences may be increasingly important as interventional devices meld
      novel materials that erode and innovations in drug delivery. Erodible materials
      may act differently if inflammation has a different temporal sequence with sex,
      and drug distribution after balloon or stent delivery might be different if the
      fibrin clearance speaks to different modes of pharmacokinetics in male and female
      swine.

PMID- 29377943
TI  - Effects of arbuscular mycorrhizal fungi and soil nutrient addition on the growth
      of Phragmites australis under different drying-rewetting cycles.
AB  - The frequency of soil drying-rewetting cycles is predicted to increase under
      future global climate change, and arbuscular mycorrhizal fungi (AMF) are
      symbiotic with most plants. However, it remains unknown how AMF affect plant
      growth under different frequencies of soil drying-rewetting cycles. We subjected
      a clonal wetland plant Phragmites australis to three frequencies of drying
      rewetting cycles (1, 2, or 4 cycles), two nutrient treatments (with or without),
      and two AMF treatments (with or without) for 64 days. AMF promoted the growth of
      P. australis, especially in the 2 cycles of the drying-rewetting treatment. AMF
      had a significant positive effect on leaf mass and number of ramets in the 2
      cycles of the drying-rewetting treatment with nutrient addition. In the 2 cycles
      of drying-rewetting treatment without nutrient addition, AMF increased leaf area
      and decreased belowground to aboveground biomass ratio. These results indicate
      that AMF may assist P. australis in coping with medium frequency of drying
      rewetting cycles, and provide theoretical guidance for predicting how wetland
      plants respond to future global climate change.

PMID- 29377944
TI  - Endovascular management of pancreatitis-related pseudoaneurysms: A review of
      techniques.
AB  - OBJECTIVES: To present the various techniques used in the management of
      pancreatitis-related pseudoaneurysms of visceral vessels. METHODS: The
      retrospective clinical study was carried out at the Department of Diagnostic and
      Interventional Radiology at Poznan University of Medical Sciences from 2011 to
      2016. The fifteen patients included in the study were diagnosed with
      pseudoaneurysms of visceral arteries, as a complication of chronic pancreatitis.
      The diagnosis was made using contrast-enhanced computed tomography, followed by
      angiography. On admission, all patients were symptomatic, with varying degrees of
      abdominal pain. One patient was haemodynamically unstable. Treatments with
      endovascular techniques were analysed, along with their efficacy and outcomes.
      Coil embolisation was performed in 5 patients. Stent graft was used in 1 patient.
      Liquid embolic agents were used in 7 cases, of which 5 patients were treated with
      thrombin injection and 2 with Squid. A combination of techniques was used in 2
      patients. RESULTS: The most common artery affected by pseudoaneurysm formation
      was the splenic artery (7/15; 46.7%), and the size of the pseudoaneurysms ranged
      from 27 mm to 85 mm. Primary technical success was achieved in 14 out of 15
      patients (93.3%). One patient required reintervention. Two patients required
      splenectomy after embolisation due to splenic ischemia. No recanalisation was
      present at the follow-up computed tomography performed after 1 to 3 weeks, and no
      mortality was observed within 30 days. CONCLUSION: Vascular complications of
      pancreatitis require accurate diagnosis and immediate treatment. Endovascular
      intervention is highly effective and is the preferred treatment option. The
      technique used is determined based on vascular anatomy and the patient's
      haemodynamic status.

PMID- 29377945
TI  - Correction: Feasibility of assessing bone matrix and mineral properties in vivo
      by combined solid-state 1H and 31P MRI.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0173995.].

PMID- 29377946
TI  - Heritability of circle of Willis variations in families with intracranial
      aneurysms.
AB  - BACKGROUND: Intracranial aneurysms more often occur in the same arterial
      territory within families. Several aneurysm locations are associated with
      specific circle of Willis variations. We investigated whether the same circle of
      Willis variations are more likely to occur in first-degree relatives than in
      unrelated individuals. METHODS: We assessed four circle of Willis variations
      (classical, A1-asymmetry, incomplete posterior communicating artery and fetal
      circulation) in two independent groups of families with familial aneurysms and
      >=2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each
      (index) family we determined the proportion of first-degree relatives with the
      same circle of Willis variation as the proband and compared it to the proportion
      of first-degree relatives of a randomly selected unrelated (comparison) family
      who had the same circle of Willis variation as the index family's proband.
      Concordance in index families and comparison families was compared with a
      conditional logistic events/trials model. The analysis was simulated 1001 times;
      we report the median concordances, odds ratios (ORs), and 95% confidence
      intervals (95%CI). The groups were analysed separately and together by meta
      analysis. RESULTS: We found a higher overall concordance in circle of Willis
      configuration in index families than in comparison families (meta-analysis, 244
      families: OR 2.2, 95%CI 1.6-3.0) mostly attributable to a higher concordance in
      incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8-4.3).
      No association was found for the other three circle of Willis variations.
      CONCLUSIONS: In two independent groups of families with familial aneurysms, the
      incomplete PcomA variation occurred more often within than between families
      suggesting heritability of this circle of Willis variation. Further studies
      should investigate genetic variants associated with circle of Willis formation.

PMID- 29377947
TI  - Correction: Lung and heart-lung transplantation in pulmonary arterial
      hypertension.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187811.].

PMID- 29377948
TI  - Correction: Short-term anti-proteinuric effect of tacrolimus is not related to
      preservation of the glomerular filtration rate in IgA nephropathy: A 5-year
      follow-up study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0188375.].

PMID- 29377950
TI  - Blurred image restoration using knife-edge function and optimal window Wiener
      filtering.
AB  - Motion blur in images is usually modeled as the convolution of a point spread
      function (PSF) and the original image represented as pixel intensities. The knife
      edge function can be used to model various types of motion-blurs, and hence it
      allows for the construction of a PSF and accurate estimation of the degradation
      function without knowledge of the specific degradation model. This paper
      addresses the problem of image restoration using a knife-edge function and
      optimal window Wiener filtering. In the proposed method, we first calculate the
      motion-blur parameters and construct the optimal window. Then, we use the
      detected knife-edge function to obtain the system degradation function. Finally,
      we perform Wiener filtering to obtain the restored image. Experiments show that
      the restored image has improved resolution and contrast parameters with clear
      details and no discernible ringing effects.

PMID- 29377949
TI  - Molecular epidemiology of human respiratory syncytial virus among children in
      Japan during three seasons and hospitalization risk of genotype ON1.
AB  - We investigated the genetic diversity, the circulation patterns, and risk for
      hospital admission of human respiratory syncytial virus (HRSV) strains in Japan
      between 2012 through 2015. During the study period, 744 HRSV-positive cases were
      identified by rapid diagnostic test. Of these, 572 samples were positive by real
      time PCR; 400 (69.9%) were HRSV-A, and 172 (30.1%) were HRSV-B. HRSV-A and -B
      alternated as the dominant strain in the subsequent seasons. Phylogenetic tree
      analysis of the second hyper-variable region of the G protein classified the HRSV
      A specimens into NA1 (n = 242) and ON1 (n = 114) genotypes and the HRSV-B
      specimens into BA9 (n = 60), and BA10 (n = 27). The ON1 genotype, containing a 72
      nucleotide duplication in the G protein's second hyper-variable region, was first
      detected in the 2012-2013 season but it predominated and replaced the older NA1
      HRSV-A in the 2014-2015 season, which also coincided with a record number of HRSV
      cases reported to the National Infectious Disease Surveillance in Japan. The risk
      of hospitalization was 6.9 times higher for the ON1 genotype compared to NA1. In
      conclusion, our data showed that the emergence and predominance of the relatively
      new ON1 genotype in Japan was associated with a record high number of cases and
      increased risk for hospitalization.

PMID- 29377951
TI  - Radiographic cup position following posterior and lateral approach to total hip
      arthroplasty. An explorative randomized controlled trial.
AB  - The two most common surgical approaches to total hip arthroplasty are the
      posterior approach and lateral approach. The surgical approach may influence cup
      positioning and restoration of the offset, which may affect the biomechanical
      properties of the hip joint. The primary aim was to compare cup position between
      posterior approach and lateral approach. Secondary aims were to compare femoral
      offset, abductor moment arm and leg length discrepancy between the two
      approaches. Eighty patients with primary hip osteoarthritis were included in a
      randomized controlled trial and assigned to total hip arthroplasty using
      posterior approach or lateral approach. Postoperative radiographs from 38
      patients in each group were included in this study for measurement of cup
      anteversion and inclination. Femoral offset, cup offset, total offset, abductor
      moment arm and leg length discrepancy were measured on preoperative and
      postoperative radiographs in 28 patients in each group. We found that mean
      anteversion was 5 degrees  larger in the posterior approach group (95% CI, -8.1
      to -1.4; p = 0.006), while mean inclination was 5 degrees  less steep (95% CI,
      2.7 to 7.2; p<0.001) compared with the lateral approach group. The posterior
      approach group had a larger mean femoral offset of 4.3mm (95% CI, -7.4 to -1.3, p
      = 0.006), mean total offset of 6.3mm (95% CI, -9.6 to -3; p<0.001) and mean
      abductor moment arm of 4.8mm (95% CI, -7.6 to -1.9; p = 0.001) compared with the
      lateral approach group. We found a larger cup anteversion but less steep cup
      inclination in the posterior approach group compared with the lateral approach
      group. Femoral offset and abductor moment arm were restored after total hip
      arthroplasty using lateral approach but significantly increased when using
      posterior approach.

PMID- 29377952
TI  - Correction: Immune-related genetic enrichment in frontotemporal dementia: An
      analysis of genome-wide association studies.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1002487.].

PMID- 29377953
TI  - Intra-cameral level of ganciclovir gel, 0.15% following topical application for
      cytomegalovirus anterior segment infection: A pilot study.
AB  - PURPOSE: To investigate the intra-cameral level of ganciclovir following topical
      application of ganciclovir gel, 0.15% for cytomegalovirus (CMV) anterior segment
      infection. DESIGN: Non-randomized, prospective, interventional clinical study.
      METHODS: Patients with active CMV anterior segment infection seen at Singapore
      National Eye Centre, confirmed by positive CMV real time PCR (RT-PCR) of the
      aqueous humor, that had not been treated with any form of ganciclovir in the
      preceding 1 month were recruited. They were treated with ganciclovir gel, 0.15%
      1cc 5 times a day. Following 6 weeks of treatment, CMV load in the aqueous humor
      was measured using CMV RT-PCR and the ganciclovir drug levels in tears and
      aqueous humor were measured using high-performance liquid chromatography-mass
      spectrometry. The clinical features of the disease activity and the central
      corneal thickness (CCT) were recorded at the baseline and post-treatment.
      RESULTS: There were 29 eyes of 29 patients, of which 23 eyes had CMV anterior
      uveitis and 6 eyes had CMV endotheliitis. At the end of week 6, 26 eyes had
      undetectable CMV titre in the aqueous humor and no anterior chamber (AC)
      activity. Two patients had an increased CMV titre and increased AC inflammation.
      Both of these patients were non-compliant with the treatment. One patient had a
      reduced CMV titre in the aqueous humor with minimal AC inflammation. The mean
      ganciclovir concentration in the aqueous humor and the tears were 17.4 +/- 30.6
      ng/ml and 20,420.9 +/- 33,120.8 ng/ml respectively. Mean CCT was 552.2 +/- 42.3
      microns. There was a weak correlation between the ganciclovir concentration in
      the aqueous humor and CCT (Spearmen's r = + 0.42, p = 0.025). There was no
      significant correlation between the ganiclovir concentration in the tears and CCT
      (Spearmen's r = + 0.39, p = 0.11). CONCLUSION: Ganciclovir levels in the aqueous
      humor was below the 50% inhibitory dose (ID50) for CMV replication, following
      topical application of the ganciclovir gel, 0.15%. TRIAL REGISTRATION: SingHealth
      Centralized Institutional Review Board, Singapore; R733/17/2010,
      ClinicalTrials.gov; NCT01647529.

PMID- 29377954
TI  - Hypoxemia in patients with idiopathic or heritable pulmonary arterial
      hypertension.
AB  - BACKGROUND: The prevalence and prognostic implications of hypoxemia either at
      rest or during six-minute walk test (6MWT) in patients with idiopathic or
      heritable pulmonary arterial hypertension (IPAH or HPAH) have not been
      systemically studied. OBJECTIVES: We sought to determine the prevalence,
      phenotypic and prognostic implications of hypoxemia in patients with IPAH and
      HPAH. METHODS: Patients with IPAH or HPAH were identified from the Cleveland
      Clinic Pulmonary Hypertension Registry. Pulse oximetry (SpO2) at rest and during
      6MWT was used to define hypoxemia at rest or during activities when measurements
      were lower than 90%, respectively. RESULTS: A total of 292 patients (age 50.6 +/-
      18.0 years, 73% females) with IPAH (88%) and HPAH (12%) were included. Of them,
      143 (49%) had SpO2 >90% at rest and during 6MWT, 89 (31%) subjects had hypoxemia
      during 6MWT and 60 (20%) had hypoxemia at rest. Patients with hypoxemia had older
      age, greater body mass index, higher prevalence of cardiovascular risk factors,
      worse functional capacity and pulmonary function tests but less severe pre
      capillary pulmonary hypertension. Individuals with hypoxemia either at rest or
      during the initial 6MWT had worse long-term survival when compared to subjects
      without hypoxemia, even when adjusting for a great number of potential
      confounders. (HR: 2.5 (95% CI: 1.54-3.98)). CONCLUSIONS: Hypoxemia in patients
      with IPAH and HPAH is associated with more comorbidities, less severe pre
      capillary pulmonary hypertension and worse survival.

PMID- 29377956
TI  - An EGR performance evaluation and decision-making approach based on grey theory
      and grey entropy analysis.
AB  - Exhaust gas recirculation (EGR) is one of the main methods of reducing NOX
      emissions and has been widely used in marine diesel engines. This paper proposes
      an optimized comprehensive assessment method based on multi-objective grey
      situation decision theory, grey relation theory and grey entropy analysis to
      evaluate the performance and optimize rate determination of EGR, which currently
      lack clear theoretical guidance. First, multi-objective grey situation decision
      theory is used to establish the initial decision-making model according to the
      main EGR parameters. The optimal compromise between diesel engine combustion and
      emission performance is transformed into a decision-making target weight problem.
      After establishing the initial model and considering the characteristics of EGR
      under different conditions, an optimized target weight algorithm based on grey
      relation theory and grey entropy analysis is applied to generate the
      comprehensive evaluation and decision-making model. Finally, the proposed method
      is successfully applied to a TBD234V12 turbocharged diesel engine, and the
      results clearly illustrate the feasibility of the proposed method for providing
      theoretical support and a reference for further EGR optimization.

PMID- 29377955
TI  - The Mexican bean beetle (Epilachna varivestis) regurgitome and insights into
      beetle-borne virus specificity.
AB  - For nearly 400 million years, insects and plants have been embattled in an
      evolutionary arms race. Insects have developed diverse feeding strategies and
      behaviors in an effort to circumvent and overcome an extensive collection of
      plant defense tactics. Sap-sucking insects often inject saliva into hosts plants,
      which contains a suite of effector proteins and even microbial communities that
      can alter the plant's defenses. Lacking salivary glands, leaf-feeding beetles
      represent an interesting group of phytophagous insects. Feeding beetles
      regurgitate onto leaf surfaces and it is thought that these oral secretions
      influence insect-plant interactions and even play a role in virus-vector
      specificity. Since the molecular and biological makeup of the regurgitant is
      virtually unknown, we carried out RNA sequencing and 16S rDNA analysis on a major
      soybean pest, Epilachna varivestis, to generate the first ever beetle
      "regurgitome" and characterize its microbiome. Interestingly, the regurgitant is
      comprised of a rich molecular assortment of genes encoding putative extracellular
      proteins involved in digestion, molting, immune defense, and detoxification. By
      carrying out plant inoculation assays, we reinforced the fundamental role of the
      regurgitant in beetle-borne virus specificity. Ultimately, these studies begin to
      characterize the importance of regurgitant in virus transmission and beetle-plant
      interactions.

PMID- 29377957
TI  - The timing of azithromycin treatment is not associated with the clinical
      prognosis of childhood Mycoplasma pneumoniae pneumonia in high macrolide
      resistant prevalence settings.
AB  - BACKGROUND: Mycoplasma pneumoniae infection is a major cause of community
      acquired pneumonia in children. We performed a retrospective study to evaluate
      the clinical impact of the timing of azithromycin treatment in children with
      Mycoplasma pneumoniae pneumonia in high macrolide-resistant prevalence settings.
      METHODS AND FINDINGS: A total of 623 patients were enrolled in this study and
      were divided into 2 groups according to the timing of azithromycin therapy.
      Children who received azithromycin within 3 days (72 hours) after the onset of
      Mycoplasma pneumoniae pneumonia were classified into the early azithromycin
      treatment group (n = 174), whereas the late azithromycin treatment group (n =
      449) comprised children treated with azithromycin more than 72 hours after
      symptom onset. We evaluated clinical prognosis according to demographic, clinical
      and laboratory characteristics. Although the early azithromycin treatment group
      exhibited a longer fever duration after azithromycin administration (7.17+/-4.12
      versus 4.82+/-3.99 days, P<0.01), the total fever duration exhibited no
      significant difference (9.02+/-4.58 versus 9.57+/-4.91 days, P = 0.212). After
      azithromycin therapy, the two groups exhibited no significant differences with
      respect to improvements in the laboratory and radiological findings (all P>0.05).
      CONCLUSION: The timing of azithromycin treatment is not associated with the
      clinical prognosis of Mycoplasma pneumoniae pneumonia in children in high
      macrolide-resistant Mycoplasma pneumoniae prevalence settings.

PMID- 29377958
TI  - Attenuation of a very virulent Marek's disease herpesvirus (MDV) by codon pair
      bias deoptimization.
AB  - Codon pair bias deoptimization (CPBD) has enabled highly efficient and rapid
      attenuation of RNA viruses. The technique relies on recoding of viral genes by
      increasing the number of codon pairs that are statistically underrepresented in
      protein coding genes of the viral host without changing the amino acid sequence
      of the encoded proteins. Utilization of naturally underrepresented codon pairs
      reduces protein production of recoded genes and directly causes virus
      attenuation. As a result, the mutant virus is antigenically identical with the
      parental virus, but virulence is reduced or absent. Our goal was to determine if
      a virus with a large double-stranded DNA genome, highly oncogenic Marek's disease
      virus (MDV), can be attenuated by CPBD. We recoded UL30 that encodes the
      catalytic subunit of the viral DNA polymerase to minimize (deoptimization),
      maximize (optimization), or preserve (randomization) the level of overrepresented
      codon pairs of the MDV host, the chicken. A fully codon pair-deoptimized UL30
      mutant could not be recovered in cell culture. The sequence of UL30 was divided
      into three segments of equal length and we generated a series of mutants with
      different segments of the UL30 recoded. The codon pair-deoptimized genes, in
      which two segments of UL30 had been recoded, showed reduced rates of protein
      production. In cultured cells, the corresponding viruses formed smaller plaques
      and grew to lower titers compared with parental virus. In contrast, codon pair
      optimized and -randomized viruses replicated in vitro with kinetics that were
      similar to those of the parental virus. Animals that were infected with the
      partially codon pair-deoptimized virus showed delayed progression of disease and
      lower mortality rates than codon pair-optimized and parental viruses. These
      results demonstrate that CPBD of a herpesvirus gene causes attenuation of the
      recoded virus and that CPBD may be an applicable strategy for attenuation of
      other large DNA viruses.

PMID- 29377959
TI  - Serum amino acid profile in patients with Parkinson's disease.
AB  - Amino acids play numerous roles in the central nervous system, serving as
      neurotransmitters, neuromodulators and regulators of energy metabolism. The free
      amino acid profile in serum of Parkinson's disease (PD) patients may be
      influenced by neurodegeneration, mitochondrial dysfunction, malabsorption in the
      gastroenteric tract and received treatment. The aim of our study was the
      evaluation of the profile of amino acid concentrations against disease
      progression. We assessed the amino acid profile in the serum of 73 patients
      divided into groups with early PD, late PD with dyskinesia and late PD without
      dyskinesia. Serum amino acid analysis was performed by high-pressure liquid
      chromatography with fluorescence detection. We observed some significant
      differences amongst the groups with respect to concentrations of alanine,
      arginine, phenylalanine and threonine, although no significant differences were
      observed between patients with advanced PD with and without dyskinesia. We
      conclude that this specific amino acid profile could serve as biochemical marker
      of PD progression.

PMID- 29377960
TI  - Human cytomegalovirus UL23 inhibits transcription of interferon-gamma stimulated
      genes and blocks antiviral interferon-gamma responses by interacting with human N
      myc interactor protein.
AB  - Interferon-gamma (IFN-gamma) represents one of the most important innate immunity
      responses in a host to combat infections of many human viruses including human
      herpesviruses. Human N-myc interactor (Nmi) protein, which has been shown to
      interact with signal transducer and activator of transcription (STAT) proteins
      including STAT1, is important for the activation of IFN-gamma induced STAT1
      dependent transcription of many genes responsible for IFN-gamma immune responses.
      However, no proteins encoded by herpesviruses have been reported to interact with
      Nmi and inhibit Nmi-mediated activation of IFN-gamma immune responses to achieve
      immune evasion from IFN-gamma responses. In this study, we show strong evidence
      that the UL23 protein of human cytomegalovirus (HCMV), a human herpesvirus,
      specifically interacts with Nmi. This interaction was identified through a yeast
      two-hybrid screen and co-immunoprecipitation in human cells. We observed that
      Nmi, when bound to UL23, was not associated with STAT1, suggesting that UL23
      binding of Nmi disrupts the interaction of Nmi with STAT1. In cells
      overexpressing UL23, we observed (a) significantly reduced levels of Nmi and
      STAT1 in the nuclei, the sites where these proteins act to induce transcription
      of IFN-gamma stimulated genes, and (b) decreased levels of the induction of the
      transcription of IFN-gamma stimulated genes. UL23-deficient HCMV mutants induced
      higher transcription of IFN-gamma stimulated genes and exhibited lower titers
      than parental and control revertant viruses expressing functional UL23 in IFN
      gamma treated cells. Thus, UL23 appears to interact directly with Nmi and inhibit
      nuclear translocation of Nmi and its associated protein STAT1, leading to a
      decrease of IFN-gamma induced responses and an increase of viral resistance to
      IFN-gamma. Our results further highlight the roles of UL23-Nmi interactions in
      facilitating viral immune escape from IFN-gamma responses and enhancing viral
      resistance to IFN antiviral effects.

PMID- 29377961
TI  - Shared and organism-specific host responses to childhood diarrheal diseases
      revealed by whole blood transcript profiling.
AB  - Globally, diarrheal diseases are a leading cause of death in children under five
      and disproportionately affect children in developing countries. Children who
      contract diarrheal diseases are rarely screened to identify the etiologic agent
      due to time and cost considerations associated with pathogen-specific screening
      and hence pathogen-directed therapy is uncommon. The development of biomarkers to
      rapidly identify underlying pathogens could improve treatment options and
      clinical outcomes in childhood diarrheal diseases. Here, we perform RNA
      sequencing on blood samples collected from children evaluated in an emergency
      room setting with diarrheal disease where the pathogen(s) present are known. We
      determine host response gene signatures specific to Salmonella, Shigella and
      rotavirus, but not E. coli, infections that distinguish them from each other and
      from healthy controls. Specifically, we observed differential expression of genes
      related to chemokine receptors or inflammasome signaling in Shigella cases, such
      as CCR3, CXCR8, and NLRC4, and interferon response genes, such as IFI44 and OASL,
      in rotavirus cases. Our findings add insight into the host peripheral immune
      response to these pathogens, and suggest strategies and limitations for the use
      host response transcript signatures for diagnosing the etiologic agent of
      childhood diarrheal diseases.

PMID- 29377963
TI  - Correction: Does proximity of women to facilities with better choice of
      contraceptives affect their contraceptive utilization in rural Ethiopia?
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187311.].

PMID- 29377962
TI  - Knowledge, attitudes and beliefs about the health hazards of biomass smoke
      exposure amongst commercial food vendors in Nigeria.
AB  - BACKGROUND: Exposure to biomass smoke is a major cause of morbidity and mortality
      in Africa. Commercial food vendors in Nigeria and elsewhere in Africa are
      commonly exposed to biomass smoke from open fire cooking both at work and home.
      Little is known about the knowledge, attitudes and beliefs of food vendors about
      the health hazards of biomass smoke exposure in Nigeria. METHODS: We did a
      descriptive cross sectional survey of the knowledge, attitudes and beliefs of
      commercial food vendors in the cities of Benin and Calabar in Nigeria. We
      recruited respondents using a multi-stage approach. Structured interviewer
      administered questionnaires were used for data collection. RESULTS: We recruited
      308 participants (164, 53.2% female). The majority 185(60.2%) were married and
      had post-primary education 206(67.4%). The average monthly income was <30,000
      Naira (US$150). Most 198(64.4%) were not aware that biomass smoke exposure is
      harmful to human health. About three-quarters (221; 71.8%) were unconcerned as to
      the effect of exposure to fumes from biomass fuels on their health. Less than
      half of respondents (110, 41.6%) believed biomass smoke was harmful to health.
      Male gender, being single, having post-primary education and preferring
      electricity or gas fuels were associated with good knowledge of the adverse
      health effects of biomass smoke exposure whilst female gender and having good
      knowledge of the adverse health effects of biomass smoke were associated with
      positive attitudes towards preventing exposure. CONCLUSION: Commercial food
      vendors in our study had limited knowledge about the adverse health effects of
      biomass smoke exposure and negative attitudes towards preventing these adverse
      health effects. We suggest an educational intervention is needed to improve this
      knowledge.

PMID- 29377965
TI  - [Caries prevention in historical perspective. Oral hygiene].
AB  - Since the beginning of the twentieth century, the ability to prevent caries has
      greatly improved. This is due to both increased knowledge about the origin of
      dental caries, and to the availability of effective aids to oral hygiene, such as
      fluoride toothpaste. The effect of oral hygiene on the general population has
      also risen because more and more people brush their teeth.

PMID- 29377964
TI  - Ethnical discrimination in Europe: Field evidence from the finance industry.
AB  - The integration of ethnical minorities has been a hotly discussed topic in the
      political, societal, and economic debate. Persistent discrimination of ethnical
      minorities can hinder successful integration. Given that unequal access to
      investment and financing opportunities can cause social and economic disparities
      due to inferior economic prospects, we conducted a field experiment on ethnical
      discrimination in the finance sector with 1,218 banks in seven European
      countries. We contacted banks via e-mail, either with domestic or Arabic sounding
      names, asking for contact details only. We find pronounced discrimination in
      terms of a substantially lower response rate to e-mails from Arabic senders.
      Remarkably, the observed discrimination effect is robust for loan- and investment
      related requests, across rural and urban locations of banks, and across
      countries.

PMID- 29377966
TI  - [Oral manifestations of Crohn's disease].
AB  - Gastrointestinal symptoms are predominant in Crohn's disease. Oral manifestations
      may also occur. The prevalence of oral manifestations varies between 0.5% and
      37%. The manifestations may coincide with or precede gastrointestinal symptoms,
      and can be subdivided into specific and non-specific lesions. In most patients,
      lesions are asymptomatic but some patients experience serious discomfort. Oral
      manifestations can be classified as specific lesions, such as diffuse lip and
      buccal swelling and cobblestones, and non-specific lesions, such as aphthous
      ulcers, pyostomatitis vegetans, caries, gingivitis and periodontitis. In many
      patients, these oral symptoms do not cause pain or discomfort and do not require
      treatment. For patients who do experience discomfort, pain caused by aphthous
      ulcers, for example, can be relieved with a lidocaine solution or a 0.1%
      dexamethasone gel, and corticosteroids can be used to treat pain caused by
      ulceration or cobblestoning. It is advisable in complex cases to consult the
      patient's gastroenterologist.

PMID- 29377967
TI  - [Replacing heavily damaged molars with the use of 3D-techniques].
AB  - Seriously damaged molars can be replaced by autotransplantation with the help of
      3D techniques. In the present case, involving an 18-year old patient, 18, 38 and
      48 were used to replace, respectively, 14, 36 and 37. Preoperatively, the width
      of the crowns and the root development of 18, 38 and 48 were analysed using 3D
      imaging. During the autotransplantation procedure, the new alveoli are formed
      with the help of replicas of the donor molars printed in 3D, in order to prevent
      iatrogenic damage to the actual donor molars.. The extra-alveolar time was less
      than 2 minutes for all donor molars. Postoperative follow-up showed physiologic
      integration of the transplanted molars. There was no ankylosis.
      Autotransplantation with the help of 3D techniques makes it possible to perform
      complex procedures with good results.

PMID- 29377968
TI  - [Preventive dentistry 9. Non-Restorative Cavity Treatment: advanced insight or
      controversial?]
AB  - Non-Restorative Cavity Treatment (NRCT) is not as popular in paediatric dentistry
      as it should be. Substantial quantitative and qualitative evidence concerning the
      treatment has now been published that testifies to the success of the treatment.
      Some healthcare providers apply the method successfully, while others have no
      trust in this non-invasive cavity treatment and continue to favour the
      restoration of carious lesions. Reasons given for this are, among others, that
      NRCT is too bothersome, the patient's (or the patient's parents') compliance is
      low and the reimbursement is inadequate. Children, however, benefit from oral
      healthcare providers who take the position that a child has a right to an
      etiological treatment that addresses the source of the caries process and that
      NRCT offers a uniquely viable treatment option for this purpose. This approach
      fits within the parameters established by professional ethics and the law. Apart
      from oral healthcare providers, all agencies involved in the profession and
      beyond have the moral and social obligation to do justice to the implied question
      of the child regarding this shift in oral healthcare.

PMID- 29377969
TI  - [The role of photodynamic therapy for the treatment of stage I and II carcinoma
      of the lip].
AB  - In this research project the outcomes of photodynamic therapy for the treatment
      of stage I and II carcinoma of the lip are presented. Retrospectively, 15
      patients diagnosed with a primary stage I or II lip carcinoma and treated with
      meta-tetra hydroxyphenyl chlorin mediated photodynamic therapy were evaluated.
      The primary outcome measure was disease free survival; the secondary outcome
      measure was the functional and aesthetic outcome after treatment. A total of 16
      primary lip carcinomas were evaluated (75% stage I; 25% stage II). In 94% of the
      primary lip carcinomas, photodynamic therapy led to a complete remission after a
      variable follow-up of 14 months to 11 years. The functional and aesthetic long
      term outcomes were considered excellent. Photodynamic therapy for the treatment
      of stage I and II lip carcinoma has a disease free survival rate comparable to
      surgery or radiotherapy and has outstanding functional and aesthetic outcomes.

PMID- 29377970
TI  - [A PhD completed. Prevention and treatment of periodontal diseases and bad
      breath].
AB  - Rinsing the mouth with water, or brushing with a dry toothbrush, does not
      contribute to an improvement in plaque removal during toothbrushing, nor does
      brushing according to a specific brushing regimen. Rinsing with water or drinking
      water has an immediate effect on bad morning breath. The combination of
      toothbrushing, tongue cleaning and a mouthwash has an effect on bad morning
      breath after 24 hours, in contrast with brushing with toothpaste only. The use of
      mouthwash with the specific ingredients chlorhexidine and essential oils has a
      positive effect on the reduction of gingivitis. The use of similar mouthwashes as
      a cooling solution in an ultrasonic device has no added effect on treatment
      results among periodontal patients. Water is an effective cooling solution.

PMID- 29377971
TI  - Patterns and Predictors of Short-Term Peripherally Inserted Central Catheter Use:
      A Multicenter Prospective Cohort Study.
AB  - BACKGROUND: The guidelines for peripherally inserted central catheters (PICCs)
      recommend avoiding insertion if the anticipated duration of use is =5 days.
      However, short-term PICC use is common in hospitals. We sought to identify
      patient, provider, and device characteristics and the clinical outcomes
      associated with short-term PICCs. METHODS: Between January 2014 and June 2016,
      trained abstractors at 52 Michigan Hospital Medicine Safety (HMS) Consortium
      sites collected data from medical records of adults that received PICCs during
      hospitalization. Patients were prospectively followed until PICC removal, death,
      or 70 days after insertion. Multivariable logistic regression models were fit to
      identify factors associated with short-term PICCs, defined as dwell time of =5
      days. Complications associated with short-term use, including major (eg, venous
      thromboembolism [VTE] or central lineassociated bloodstream infection [CLABSI])
      or minor (eg, catheter occlusion, tip migration) events were assessed. RESULTS:
      Of the 15,397 PICCs placed, 3902 (25.3%) had a dwell time of =5 days. Most
      (95.5%) short-term PICCs were removed during hospitalization. Compared to PICCs
      placed for >5 days, variables associated with short-term PICCs included difficult
      venous access (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.40-1.69),
      multilumen devices (OR, 1.53; 95% CI, 1.39-1.69), and teaching hospitals (OR,
      1.25; 95% CI, 1.04-1.52). Among those with short-term PICCs, 374 (9.6%)
      experienced a complication, including 99 (2.5%) experiencing VTE and 17 (0.4%)
      experiencing CLABSI events. The most common minor complications were catheter
      occlusion (4%) and tip migration (2.2%). CONCLUSION: Short-term use of PICCs is
      common and associated with patient, provider, and device factors. As PICC
      placement, even for brief periods, is associated with complications, efforts
      targeted at factors underlying such use appear necessary.

PMID- 29377973
TI  - Understanding mortality in care facilities-the role of good data.

PMID- 29377972
TI  - Recommendations on the Use of Ultrasound Guidance for Adult Thoracentesis: A
      Position Statement of the Society of Hospital Medicine.
AB  - Executive Summary: 1) We recommend that ultrasound should be used to guide
      thoracentesis to reduce the risk of complications, the most common being
      pneumothorax. 2) We recommend that ultrasound guidance should be used to increase
      the success rate of thoracentesis. 3) We recommend that ultrasound-guided
      thoracentesis should be performed or closely supervised by experienced operators.
      4) We suggest that ultrasound guidance be used to reduce the risk of
      complications from thoracentesis in mechanically ventilated patients. 5) We
      recommend that ultrasound should be used to identify the chest wall, pleura,
      diaphragm, lung, and subdiaphragmatic organs throughout the respiratory cycle
      before selecting a needle insertion site. 6) We recommend that ultrasound should
      be used to detect the presence or absence of an effusion and approximate the
      volume of pleural fluid to guide clinical decision-making. 7) We recommend that
      ultrasound should be used to detect complex sonographic features, such as
      septations, to guide clinical decision-making regarding the timing and method of
      pleural drainage. 8) We suggest that ultrasound be used to measure the depth from
      the skin surface to the parietal pleura to help select an appropriate length
      needle and determine the maximum needle insertion depth. 9) We suggest that
      ultrasound be used to evaluate normal lung sliding pre- and postprocedure to rule
      out pneumothorax. 10) We suggest avoiding delay or interval change in patient
      position from the time of marking the needle insertion site to performing the
      thoracentesis. 11) We recommend against performing routine postprocedure chest
      radiographs in patients who have undergone thoracentesis successfully with
      ultrasound guidance and are asymptomatic with normal lung sliding postprocedure.
      12) We recommend that novices who use ultrasound guidance for thoracentesis
      should receive focused training in lung and pleural ultrasonography and hands-on
      practice in procedural technique. 13) We suggest that novices undergo simulation
      based training prior to performing ultrasound-guided thoracentesis on patients.
      14) Learning curves for novices to become competent in lung ultrasound and
      ultrasound-guided thoracentesis are not completely understood, and we recommend
      that training should be tailored to the skill acquisition of the learner and the
      resources of the institution.

PMID- 29377974
TI  - Decreasing Invalid Symptom Reporting: A Comment on Horner, Turner, VanKirk, and
      Denning (2017).

PMID- 29377975
TI  - Single-molecule manipulation and detection.
AB  - Compared to conventional ensemble methods, studying macromolecules at single
      molecule level can reveal extraordinary clear and even surprising views for a
      biological reaction. In the past 20 years, single-molecule techniques have been
      undergoing a very rapid development, and these cutting edge technologies have
      revolutionized the biological research by facilitating single-molecule
      manipulation and detection. Here we give a brief review about these advanced
      techniques, including optical tweezers, magnetic tweezers, atomic force
      microscopy (AFM), hydrodynamic flow-stretching assay, and single-molecule
      fluorescence resonance energy transfer (smFRET). We are trying to describe their
      basic principles and provide a few examples of applications for each technique.
      This review aims to give a rather introductory survey of single-molecule
      techniques for audiences with biological or biophysical background.

PMID- 29377977
TI  - Visit-to-visit blood pressure variability: added 'VALUE' as a risk marker in low-
      and high-risk patients.

PMID- 29377978
TI  - Re: Video-assisted thoracoscopic surgery yields better outcomes than thoracotomy
      for anatomical lung resection in Brazil: a propensity score-matching analysis
      using the Brazilian Society of Thoracic Surgery database.

PMID- 29377979
TI  - MiR-147b inhibits cell viability and promotes apoptosis of rat H9c2
      cardiomyocytes via down-regulating KLF13 expression.
AB  - Recently, microRNAs (miRNAs) have been shown to involve in the process of heart
      failure. This study aims to investigate the functional role of miR-147b in rat
      H9c2 cardiomyocytes and explore the underlying molecular mechanisms. Cell
      viability of H9c2 cells was detected by MTT assay. Cell apoptosis was detected by
      flow cytometry. Expression of miR-147b and KLF13 mRNA was detected by
      quantitative real-time PCR. The relationship between miR-147b and KLF13 was
      verified by dual-luciferase reporter assay. Protein levels were detected by
      western blot analysis. It was found that H2O2 inhibited cell viability and
      promoted cell apoptosis of H9c2 cells in a concentration-dependent manner. MiR
      147b overexpression suppressed cell viability and increased apoptosis in H9c2
      cells, while knock-down of miR-147b increased cell viability and reduced
      apoptosis in H2O2-treated H9c2 cells. Luciferase reporter assay and in vitro
      functional assay showed that KLF13 was a downstream target of miR-147b, and KLF13
      knock-down suppressed cell viability and induced apoptosis in H9c2 cells.
      Enforced expression of KLF13 restored the effects of miR-147b overexpression on
      cell viability and apoptosis in H9c2 cells. MiR-147b modulated the expression
      levels of apoptosis-related proteins, and the effects of miR-147b overexpression
      on apoptosis-related proteins levels were prevented by enforced expression of
      KLF13 in H9c2 cells. The in vivo experiments showed that miR-147b was up
      regulated, and KLF13 was down-regulated in the myocardial tissues from rats with
      chronic heart failure. Collectively, miR-147b inhibits viability and promotes
      cell apoptosis by targeting KLF13 in H9c2 cells, which may be associated with the
      pathogenesis of heart failure.

PMID- 29377980
TI  - Correlation between circulating endothelial progenitor cells and serum
      carcinoembryonic antigen level in colorectal cancer.
AB  - Circulating endothelial progenitor cells (cEPCs) play an important role in cancer
      development. Previous studies showed that serum carcinoembryonic antigen (CEA)
      levels and the number of circulating endothelial progenitor cells (cEPCs) in the
      peripheral blood are both involved in tumor neoangiogenesis, and can be used for
      monitoring tumor progression, recurrence, metastasis, and therapeutic responses.
      However, the clinical relevance of these biomarkers remains unknown. In this
      study, 40 colorectal cancer (CRC) patients and 17 healthy volunteers were
      recruited and the amount of cEPCs in the peripheral blood was measured by flow
      cytometry. The serum CEA level was determined by CEA-RIACT assay. Results showed
      that cEPC level positively correlated with the stage of the disease, but not with
      the age and gender of the patients. Moreover, patients with higher serum CEA
      levels had higher cEPC levels. These results provide clinical evidence for a
      correlation between two commonly used biomarkers. Further understanding the role
      of serum CEA in cEPC-mediated tumor vascularization may improve clinical CRC
      diagnosis and provide useful insights into the design of therapeutic
      interventions that target tumor vasculature.

PMID- 29377981
TI  - Computational prediction of drug-target interactions using chemogenomic
      approaches: an empirical survey.
AB  - Computational prediction of drug-target interactions (DTIs) has become an
      essential task in the drug discovery process. It narrows down the search space
      for interactions by suggesting potential interaction candidates for validation
      via wet-lab experiments that are well known to be expensive and time-consuming.
      In this article, we aim to provide a comprehensive overview and empirical
      evaluation on the computational DTI prediction techniques, to act as a guide and
      reference for our fellow researchers. Specifically, we first describe the data
      used in such computational DTI prediction efforts. We then categorize and
      elaborate the state-of-the-art methods for predicting DTIs. Next, an empirical
      comparison is performed to demonstrate the prediction performance of some
      representative methods under different scenarios. We also present interesting
      findings from our evaluation study, discussing the advantages and disadvantages
      of each method. Finally, we highlight potential avenues for further enhancement
      of DTI prediction performance as well as related research directions.

PMID- 29377982
TI  - Functional capacity and health-related quality of life outcomes post
      transcatheter aortic valve replacement: a systematic review and meta-analysis.
AB  - Background: transcatheter aortic valve replacement (TAVR) provides prognostic
      benefit for high surgical-risk patients with severe aortic stenosis (AS), yet the
      impact to patient outcomes is far less understood. Method: we performed a
      systematic review and meta-analysis to evaluate functional capacity and health
      related quality of life (HRQoL) outcomes for patients up to 12 months post TAVR.
      A total of 20 eligible publications, comprising randomised-controlled trials,
      observational studies and a registry study were identified from electronic
      databases, including MEDLINE, EMBASE, Cochrane Library and others (inception to
      February 2017). Results: the total sample was 2,775 with a mean age of 81.8 +/-
      2.1 years, more than half (52%) were female and high surgical risk 9.6 +/- 4.3%
      mean STS (Society of Thoracic Surgeons risk model). Post TAVR, patients had
      significant improvement in functional capacity of >40 m in the 6-minute walk test
      (6MWT) (95% confidence interval (CI) 9.69-73.28) and a clinically meaningful
      increase in ability to perform daily physical-based tasks (Duke Activity Status
      Index (DASI), mean difference (MD) increase 5.42 points, 95% CI 3.16-7.68). HRQoL
      improved consistently following TAVR regardless of measure used. Significant
      increases occurred in the physical component summary scores (PCS) of the short
      form (SF) health surveys (MD increase 10.45 (SF36) and 10.14 (SF12) points).
      Conclusion: functional capacity and HRQoL improved substantially following TAVR,
      despite evolving patient selection criteria, thus TAVR continues to provide a
      directly beneficial option for severe AS patients.

PMID- 29377983
TI  - Titin cardiomyopathy leads to altered mitochondrial energetics, increased
      fibrosis and long-term life-threatening arrhythmias.
AB  - Aims: Truncating titin variants (TTNtv) are the most prevalent genetic cause of
      dilated cardiomyopathy (DCM). We aim to study clinical parameters and long-term
      outcomes related to the TTNtv genotype and determine the related molecular
      changes at tissue level in TTNtv DCM patients. Methods and results: A total of
      303 consecutive and extensively phenotyped DCM patients (including cardiac
      imaging, Holter monitoring, and endomyocardial biopsy) underwent DNA sequencing
      of 47 cardiomyopathy-associated genes including TTN, yielding 38 TTNtv positive
      (13%) patients. At long-term follow-up (median of 45 months, up to 12 years),
      TTNtv DCM patients had increased ventricular arrhythmias compared to other DCM,
      but a similar survival. Arrhythmias are especially prominent in TTNtv patients
      with an additional environmental trigger (i.e. virus infection, cardiac
      inflammation, systemic disease, toxic exposure). Importantly, cardiac mass is
      reduced in TTNtv patients, despite similar cardiac function and dimensions at
      cardiac magnetic resonance. These enhanced life-threatening arrhythmias and
      decreased cardiac mass in TTNtv DCM patients go along with significant cardiac
      energetic and matrix alterations. All components of the mitochondrial electron
      transport chain are significantly upregulated in TTNtv hearts at RNA-sequencing.
      Also, interstitial fibrosis was augmented in TTNtv patients at histological and
      transcript level. Conclusion: Truncating titin variants lead to pronounced
      cardiac alterations in mitochondrial function, with increased interstitial
      fibrosis and reduced hypertrophy. Those structural and metabolic alterations in
      TTNtv hearts go along with increased ventricular arrhythmias at long-term follow
      up, with a similar survival and overall cardiac function.

PMID- 29377984
TI  - Longer inter-lead electrical delay is associated with response to cardiac
      resynchronization therapy in patients with presumed optimal left ventricular lead
      position.
AB  - Aims: In a randomized trial of cardiac resynchronization therapy (CRT), a
      presumed optimal left ventricular (LV) lead position close to the latest
      mechanically activated non-scarred myocardium was achieved in 98% of patients by
      standard implantation. We evaluated whether inter-lead electrical delay (IED) was
      associated with response to CRT in these patients. Methods and results: We
      prospectively included 160 consecutive patients undergoing CRT. Pre-implant
      speckle-tracking echocardiography radial strain and 99mTc myocardial perfusion
      imaging determined the latest mechanically activated non-scarred myocardial
      segment. We measured procedural IED as the time interval between sensed signals
      in right ventricular and LV lead electrograms. All patients had LV pacing site
      concordant or adjacent to the latest mechanically activated non-scarred segment
      verified by cardiac computed tomography. Response to CRT was defined as >=15%
      reduction in LV end-systolic volume at 6 months follow-up. Selecting a practical
      IED cut-off value of 100 ms, more patients with long IED than patients with short
      IED responded to CRT (87 vs. 68%; P = 0.004). In multivariate logistic regression
      analysis, IED >=100 ms remained associated with CRT response after adjusting for
      baseline characteristics, including QRS duration and scar burden [odds ratio 3.19
      (1.24-8.17); P = 0.01]. Categorizing IED by tertiles, CRT response improved with
      longer IED (P = 0.03). Comparable response rates were observed in patients with a
      concordant and adjacent LV lead position. Conclusion: A longer IED was associated
      with more pronounced LV reverse remodelling response in CRT recipients with a
      presumed optimal LV lead position concordant or adjacent to the latest
      mechanically activated non-scarred segment.

PMID- 29377985
TI  - Cancer therapy-induced cardiomyopathy: can human induced pluripotent stem cell
      modelling help prevent it?
AB  - Cardiotoxic effects from cancer therapy are a major cause of morbidity during
      cancer treatment. Unexpected toxicity can occur during treatment and/or after
      completion of therapy, into the time of cancer survivorship. While older drugs
      such as anthracyclines have well-known cardiotoxic effects, newer drugs such as
      tyrosine kinase inhibitors, proteasome inhibitors, and immunotherapies also can
      cause diverse cardiovascular and metabolic complications. Human induced
      pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly being
      used as instruments for disease modelling, drug discovery, and mechanistic
      toxicity studies. Promising results with hiPSC-CM chemotherapy studies are
      raising hopes for improving cancer therapies through personalized medicine and
      safer drug development. Here, we review the cardiotoxicity profiles of common
      chemotherapeutic agents as well as efforts to model them in vitro using hiPSC
      CMs.

PMID- 29377986
TI  - Balloon Dilation of Intrinsic Small Bowel Strictures: Still Doubts About Its
      Efficacy?

PMID- 29377987
TI  - Antiarrhythmic effect of antazoline in experimental models of acquired short- and
      long-QT-syndromes.
AB  - Aims: Antazoline is a first-generation antihistamine with antiarrhythmic
      properties. This study examines potential electrophysiological effects of
      antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS). Methods and
      results: Sixty-five rabbit hearts were Langendorff-perfused. Action potential
      duration at 90% of repolarization (APD90), QT-interval, spatial dispersion
      (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener
      pinacidil (1 uM, n = 14) reduced APD90 (-14 ms, P < 0.01), QT-interval (-14 ms, P
      < 0.01), and ERP (-11 ms, P < 0.01), thus simulating acquired SQTS. Additional
      infusion of 20 uM antazoline prolonged repolarization. Under baseline conditions,
      ventricular fibrillation (VF) was inducible in 5 of 14 hearts (10 episodes) and
      in 5 of 14 pinacidil-treated hearts (21 episodes, P = ns). Antazoline
      significantly reduced induction of VF (0 episodes, P < 0.05 each). Further 17
      hearts were perfused with 100 uM sotalol and 17 hearts with 300 uM erythromycin
      to induce acquired LQTS2. In both groups, prolongation of APD90, QT-interval, and
      ERP was observed. Spatial dispersion was increased (sotalol: +26 ms, P < 0.01;
      erythromycin: +31 ms, P < 0.01). Additional infusion of antazoline reduced DISP
      (sotalol: -22 ms, P < 0.01; erythromycin: -26 ms, P < 0.01). Torsade de pointes
      (TdP) occurred in 6 of 17 sotalol-treated (22 episodes, P < 0.05 each) and in 8
      of 17 erythromycin-treated hearts (96 episodes P < 0.05 each). Additional
      infusion of antazoline completely suppressed TdP in both groups (P < 0.05 each).
      Acquired LQTS3 was induced by veratridine (0.5 uM, n = 17) and similar results
      were obtained (APD90: +24 ms, P < 0.01, QT-interval: +58 ms, P < 0.01, DISP: +38
      ms, P < 0.01). Torsade de pointes occurred in 10 of 17 hearts (41 episodes, P <
      0.05 each). Antazoline significantly reduced TdP (2 of 17 hearts, 4 episodes, P <
      0.05 each). Conclusion: Antazoline significantly reduced induction of VF in an
      experimental model of acquired SQTS. In three experimental models of acquired
      LQTS, antazoline effectively suppressed TdP.

PMID- 29377988
TI  - Outcomes from the Delphi process of the Thoracic Robotic Curriculum Development
      Committee.
AB  - OBJECTIVES: As the adoption of robotic procedures becomes more widespread,
      additional risk related to the learning curve can be expected. This article
      reports the results of a Delphi process to define procedures to optimize robotic
      training of thoracic surgeons and to promote safe performance of established
      robotic interventions as, for example, lung cancer and thymoma surgery. METHODS:
      In June 2016, a working panel was spontaneously created by members of the
      European Society of Thoracic Surgeons (ESTS) and European Association for Cardio
      Thoracic Surgery (EACTS) with a specialist interest in robotic thoracic surgery
      and/or surgical training. An e-consensus-finding exercise using the Delphi
      methodology was applied requiring 80% agreement to reach consensus on each
      question. Repeated iterations of anonymous voting continued over 3 rounds.
      RESULTS: Agreement was reached on many points: a standardized robotic training
      curriculum for robotic thoracic surgery should be divided into clearly defined
      sections as a staged learning pathway; the basic robotic curriculum should
      include a baseline evaluation, an e-learning module, a simulation-based training
      (including virtual reality simulation, Dry lab and Wet lab) and a robotic theatre
      (bedside) observation. Advanced robotic training should include e-learning on
      index procedures (right upper lobe) with video demonstration, access to video
      library of robotic procedures, simulation training, modular console training to
      index procedure, transition to full-procedure training with a proctor and final
      evaluation of the submitted video to certified independent examiners.
      CONCLUSIONS: Agreement was reached on a large number of questions to optimize and
      standardize training and education of thoracic surgeons in robotic activity. The
      production of the content of the learning material is ongoing.

PMID- 29377989
TI  - Genetic Complexity of Cortical Structure: Differences in Genetic and
      Environmental Factors Influencing Cortical Surface Area and Thickness.
AB  - Quantifying the genetic architecture of the cerebral cortex is necessary for
      understanding disease and changes to the brain across the lifespan. Prior work
      shows that both surface area (SA) and cortical thickness (CT) are heritable.
      However, we do not yet understand the extent to which region-specific genetic
      factors (i.e., independent of global effects) play a dominant role in the
      regional patterning or inter-regional associations across the cortex. Using a
      population sample of young adult twins (N = 923), we show that the heritability
      of SA and CT varies widely across regions, generally independent of measurement
      error. When global effects are controlled for, we detected a complex pattern of
      genetically mediated clusters of inter-regional associations, which varied
      between hemispheres. There were generally weak associations between the SA of
      different regions, except within the occipital lobe, whereas CT was positively
      correlated within lobar divisions and negatively correlated across lobes, mostly
      due to genetic covariation. These findings were replicated in an independent
      sample of twins and siblings (N = 698) from the Human Connectome Project. The
      different genetic contributions to SA and CT across regions reveal the value of
      quantifying sources of covariation to appreciate the genetic complexity of
      cortical structures.

PMID- 29377990
TI  - HPViewer: sensitive and specific genotyping of human papillomavirus in
      metagenomic DNA.
AB  - Motivation: Shotgun DNA sequencing provides sensitive detection of all 182 HPV
      types in tissue and body fluid. However, existing computational methods either
      produce false positives misidentifying HPV types due to shared sequences among
      HPV, human and prokaryotes, or produce false negative since they identify HPV by
      assembled contigs requiring large abundant of HPV reads. Results: We designed
      HPViewer with two custom HPV reference databases masking simple repeats and
      homology sequences respectively and one homology distance matrix to hybridize
      these two databases. It directly identified HPV from short DNA reads rather than
      assembled contigs. Using 100 100 simulated samples, we revealed that HPViewer was
      robust for samples containing either high or low number of HPV reads. Using 12
      shotgun sequencing samples from respiratory papillomatosis, HPViewer was equal to
      VirusTAP, and Vipie and better than HPVDetector with the respect to specificity
      and was the most sensitive method in the detection of HPV types 6 and 11. We
      demonstrated that contigs-based approaches had disadvantages of detection of HPV.
      In 1573 sets of metagenomic data from 18 human body sites, HPViewer identified
      104 types of HPV in a body-site associated pattern and 89 types of HPV co
      occurring in one sample with other types of HPV. We demonstrated HPViewer was
      sensitive and specific for HPV detection in metagenomic data. Availability and
      implementation: HPViewer can be accessed at https://github.com/yuhanH/HPViewer/.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29377991
TI  - Subthreshold Activity Underlying the Diversity and Selectivity of the Primary
      Auditory Cortex Studied by Intracellular Recordings in Awake Marmosets.
AB  - Extracellular recording studies have revealed diverse and selective neural
      responses in the primary auditory cortex (A1) of awake animals. However, we have
      limited knowledge on subthreshold events that give rise to these responses,
      especially in non-human primates, as intracellular recordings in awake animals
      pose substantial technical challenges. We developed a novel intracellular
      recording technique in awake marmosets to systematically study subthreshold
      activity of A1 neurons that underlies their diverse and selective spiking
      responses. Our findings showed that in contrast to predominantly transient
      depolarization observed in A1 of anesthetized animals, both transient and
      sustained depolarization (during or beyond the stimulus period) were observed.
      Comparing with spiking responses, subthreshold responses were often longer
      lasting in duration and more broadly tuned in frequency, and showed narrower
      intensity tuning in non-monotonic neurons and lower response threshold in
      monotonic neurons. These observations demonstrated the enhancement of stimulus
      selectivity from subthreshold to spiking responses in individual A1 neurons.
      Furthermore, A1 neurons classified as regular- or fast-spiking subpopulation
      based on their spike shapes exhibited distinct response properties in frequency
      and intensity domains. These findings provide valuable insights into cortical
      integration and transformation of auditory information at the cellular level in
      auditory cortex of awake non-human primates.

PMID- 29377992
TI  - Genetic and epigenetic factors which modulate differentiation propensity in human
      pluripotent stem cells.
AB  - BACKGROUND: Human pluripotent stem cell (hPSC) lines are known to have a bias in
      their differentiation. This gives individual cell lines a propensity to
      preferentially differentiate towards one germ layer or cell type over others.
      Chromosomal aberrations, mitochondrial mutations, genetic diversity and
      epigenetic variance are the main drivers of this phenomenon, and can lead to a
      wide range of phenotypes. OBJECTIVE AND RATIONALE: Our aim is to provide a
      comprehensive overview of the different factors which influence differentiation
      propensity. Specifically, we sought to highlight known genetic variances and
      their mechanisms, in addition to more general observations from larger
      abnormalities. Furthermore, we wanted to provide an up-to-date list of a growing
      number of predictive indicators which are able to identify differentiation
      propensity before the initiation of differentiation. As differentiation
      propensity can lead to difficulties in both research as well as clinical
      translation, our thorough overview could be a useful tool. SEARCH METHODS:
      Combinations of the following key words were applied as search criteria in the
      PubMed database: embryonic stem cells, induced pluripotent stem cells,
      differentiation propensity (also: potential, efficiency, capacity, bias,
      variability), epigenetics, chromosomal abnormalities, genetic aberrations, X
      chromosome inactivation, mitochondrial function, mitochondrial metabolism,
      genetic diversity, reprogramming, predictive marker, residual stem cell, clinic.
      Only studies in English were included, ranging from 2000 to 2017, with a majority
      ranging from 2010 to 1017. Further manuscripts were added from cross-references.
      OUTCOMES: Differentiation propensity is affected by a wide variety of
      (epi)genetic factors. These factors clearly lead to a loss of differentiation
      capacity, preference towards certain cell types and oftentimes, phenotypes which
      begin to resemble cancer. Broad changes in (epi)genetics, such as aneuploidies or
      wide-ranging modifications to the epigenetic landscape tend to lead to extensive,
      less definite changes in differentiation capacity, whereas more specific
      abnormalities often have precise ramifications in which certain cell types become
      more preferential. Furthermore, there appears to be a greater, though often less
      considered, contribution to differentiation propensity by factors such as
      mitochondria and inherent genetic diversity. Varied differentiation capacity can
      also lead to potential consequences in the clinical translation of hPSC,
      including the occurrence of residual undifferentiated stem cells, and the
      transplantation of potentially transformed cells. WIDER IMPLICATIONS: As hPSC
      continue to advance towards the clinic, our understanding of them progresses as
      well. As a result, the challenges faced become more numerous, but also more
      clear. If the transition to the clinic is to be achieved with a minimum number of
      potential setbacks, thorough evaluation of the cells will be an absolute
      necessity. Altered differentiation propensity represents at least one such
      hurdle, for which researchers and eventually clinicians will need to find
      solutions. Already, steps are being taken to tackle the issue, though further
      research will be required to evaluate any long-term risks it poses.

PMID- 29377993
TI  - Perimenarchal air pollution exposure and menstrual disorders.
AB  - STUDY QUESTION: What is the association between perimenarchal exposure to total
      suspended particulate (TSP) in air, menstrual irregularity phenotypes and time to
      menstrual cycle regularity? SUMMARY ANSWER: Exposures to TSP during high school
      are associated with slightly increased odds of menstrual irregularity and longer
      time to regularity in high school and early adulthood. WHAT IS KNOWN ALREADY: The
      menstrual cycle is responsive to hormonal regulation. Particulate matter air
      pollution has demonstrated hormonal activity. However, it is not known if air
      pollution is associated with menstrual cycle regularity. STUDY DESIGN, SIZE,
      DURATION: Cross sectional study of 34 832 of the original 116 430 women (29.91%)
      enrolled in 1989 from the Nurses' Health Study II (NHSII). The follow-up rate for
      this analytic sample was 97.76% at the 1991 survey. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Annual averages of TSP were available for each year of high
      school attendance. We created three case definitions including high school
      menstrual irregularity and androgen excess. The time to menstrual cycle
      regularity was reported by participants as <1 year, 1-2 years, 3-4 years, 5 years
      or longer, or never on the baseline questionnaire. Odds ratios and 95% confidence
      intervals (CI) were calculated for 45 MUg/m3 increases in TSP exposure, adjusted
      for risk factors for menstrual irregularity. MAIN RESULTS AND THE ROLE OF CHANCE:
      In multivariable adjusted models, we observed that for every 45 MUg/m3 increase
      in average high school TSP there was an increased odds (95%CI) of 1.08 (1.03
      1.14), 1.08 (1.02-1.15) and 1.10 (0.98-1.25) for moderate, persistent, and
      persistent with androgen excess irregularity phenotypes, respectively. TSP was
      also associated with a longer time to cycle regularity, with stronger results
      among women with older ages at menarche and those living in the Northeast or the
      West. LIMITATIONS, REASONS FOR CAUTION: The outcomes of menstrual regularity and
      time to cycle regularity were retrospectively assessed outcomes and may be
      susceptible to recall bias. There is also the potential for selection bias, as
      women had to live until 2011 to provide addresses. WIDER IMPLICATIONS OF THE
      FINDINGS: Temporal exposure to air pollution in the adolescent and early
      adulthood window may be especially important, given its association with
      phenotypes of menstrual irregularity. The data from this study agrees with
      existing literature regarding air pollution and reproductive tract diseases.
      STUDY FUNDING/COMPETING INTEREST(S): Shruthi Mahalingaiah: Reproductive Scientist
      Development Program HD000849, and a research grant from the Boston University
      Department of Obstetrics and Gynecology, Stacey Missmer: R01HD57210 from the
      National Institute of Child Health and Human Development and the Massachusetts
      Institute of Technology Center for Environmental Health Sciences Translational
      Pilot Project Program, R01CA50385 from the National Cancer Institute, Jaime Hart
      and Francine Laden: 5R01ES017017 from the National Institute for Environmental
      Health Sciences, Jaime Hart: P30 ES00002 from the National Institute for
      Environmental Health Sciences at the National Institute of Health, The Nurses'
      Health Study II is supported by infrastructure grant UM1CA176726 from the
      National Cancer Institute, NIH, U.S. Department of Health and Human Services The
      authors have no conflicts of interest to declare.

PMID- 29377994
TI  - Basic mechanisms of vascularization in endometriosis and their clinical
      implications.
AB  - BACKGROUND: Vascularization is a major hallmark in the pathogenesis of
      endometriosis. An increasing number of studies suggests that multiple mechanisms
      contribute to the vascularization of endometriotic lesions, including
      angiogenesis, vasculogenesis and inosculation. OBJECTIVE AND RATIONALE: In this
      review, we provide an overview of the basic mechanisms of vascularization in
      endometriosis and give special emphasis on their future clinical implications in
      the diagnosis and therapy of the disease. SEARCH METHODS: Literature searches
      were performed in PubMed for English articles with the key words 'endometriosis',
      'endometriotic lesions', 'angiogenesis', 'vascularization', 'vasculogenesis',
      'endothelial progenitor cells' and 'inosculation'. The searches included both
      animal and human studies. No restriction was set for the publication date.
      OUTCOMES: The engraftment of endometriotic lesions is typically associated with
      angiogenesis, i.e. the formation of new blood vessels from pre-existing ones.
      This angiogenic process underlies the complex regulation by angiogenic growth
      factors and hormones, which activate intracellular pathways and associated
      signaling molecules. In addition, circulating endothelial progenitor cells (EPCs)
      are mobilized from the bone marrow and recruited into endometriotic lesions,
      where they are incorporated into the endothelium of newly developing
      microvessels, referred to as vasculogenesis. Finally, preformed microvessels in
      shed endometrial fragments inosculate with the surrounding host microvasculature,
      resulting in a rapid blood supply to the ectopic tissue. These vascularization
      modes offer different possibilities for the establishment of novel diagnostic and
      therapeutic approaches. Angiogenic growth factors and EPCs may serve as
      biomarkers for the diagnosis and classification of endometriosis. Blood vessel
      formation and mature microvessels in endometriotic lesions may be targeted by
      means of anti-angiogenic compounds and vascular-disrupting agents. WIDER
      IMPLICATIONS: The establishment of vascularization-based approaches in the
      management of endometriosis still represents a major challenge. For diagnostic
      purposes, reliable angiogenic and vasculogenic biomarker panels exhibiting a high
      sensitivity and specificity must be identified. For therapeutic purposes, novel
      compounds selectively targeting the vascularization of endometriotic lesions
      without inducing severe side effects are required. Recent progress in the field
      of endometriosis research indicates that these goals may be achieved in the near
      future.

PMID- 29377995
TI  - High-glucose concentrations change DNA methylation levels in human IVM oocytes.
AB  - STUDY QUESTION: What are the effects of high-glucose concentrations on DNA
      methylation of human oocytes? SUMMARY ANSWER: High-glucose concentrations altered
      DNA methylation levels of Peg3 and Adiponectin in human in vitro maturation
      oocytes. WHAT IS KNOWN ALREADY: Maternal diabetes has a detrimental influence on
      oocyte quality including epigenetic modifications, as shown in non-human
      mammalian species. STUDY DESIGN, SIZE, DURATION: Immature metaphase I (MI) stage
      oocytes of good quality were retrieved from patients who had normal ovarian
      potential and who underwent ICSI in the Reproductive Medicine Center of People's
      Hospital of Zhengzhou University. MI oocytes were cultured in medium with
      different glucose concentrations (control, 10 mM and 15 mM) in vitro and 48 h
      later, oocytes with first polar body extrusion were collected to check the DNA
      methylation levels. PARTICIPANTS/MATERIALS, SETTING, METHODS: MI oocytes
      underwent in vitro maturation (IVM) at 37 degrees C with 5% mixed gas for 48 h.
      Then the mature oocytes were treated with bisulfite buffer. Target sequences were
      amplified using nested or half-nested PCR and the DNA methylation status was
      tested using combined bisulfite restriction analysis (COBRA) and bisulfite
      sequencing (BS). MAIN RESULTS AND THE ROLE OF CHANCE: High-glucose concentrations
      significantly decreased the first polar body extrusion rate. Compared to
      controls, the DNA methylation levels of Peg3 in human IVM oocytes were
      significantly higher in 10 mM (P < 0.001) and 15 mM (P < 0.001) concentrations of
      glucose. But the DNA methylation level of H19 was not affected by high-glucose
      concentrations in human IVM oocytes. We also found that there was a decrease in
      DNA methylation levels in the promoter of adiponectin in human IVM oocytes
      between controls and oocytes exposed to 10 mM glucose (P = 0.028). LARGE SCALE
      DATA: N/A. LIMITATIONS REASONS FOR CAUTION: It is not clear whether the
      alterations are beneficial or not for the embryo development and offspring
      health. The effects of high-glucose concentrations on the whole process of oocyte
      maturation are still not elucidated. Another issue is that the number of oocytes
      used in this study was limited. WIDER IMPLICATIONS OF THE FINDINGS: This is the
      first time that the effects of high-glucose concentration on DNA methylation of
      human oocytes have been elucidated. Our result indicates that in humans, the high
      risk of chronic diseases in offspring from diabetic mothers may originate from
      abnormal DNA modifications in oocytes. STUDY FUNDING/COMPETING INTEREST(S): This
      work was supported by the fund of National Natural Science Foundation of China
      (81401198) and Doctor Foundation of Qingdao Agricultural University (1116008).The
      authors declare that there are no potential conflicts of interest relevant to
      this article.

PMID- 29377996
TI  - Toxicological Drug Screening using Paper Spray High-Resolution Tandem Mass
      Spectrometry (HR-MS/MS).
AB  - Immunoassays and high-performance liquid chromatography (HPLC) coupled with mass
      spectrometry (MS) are both widely used methods for drug screening in toxicology.
      We investigated an alternative approach for rapid drug screening: paper spray MS
      (PS-MS). In paper spray, the biofluid sample is spotted onto a paper substrate.
      Upon application of a spray solvent and an electric potential, extraction and
      ionization occur directly from the paper without any need for additional sample
      preparation. We developed two paper spray high-resolution MS/MS targeted drug
      screening assays using a quadrupole-orbitrap mass spectrometer, one the positive
      ion mode and one in the negative ion mode. In the positive ion mode, over 130
      drugs and drug metabolites were semi-quantitatively screened at sub-toxic
      concentrations in a single 2.5 min analysis. Limits of detection and calibration
      performances for each target compound are reported. The PS-MS/MS assay was tested
      on authentic postmortem specimens, and its screening ability and semi
      quantitative performance were evaluated against independent LC-MS-MS screening
      and confirmation assays with good agreement. The paper spray MS/MS showed good
      qualitative agreement with LC-MS-MS; the true positive rate of paper spray MS/MS
      was 92%, and the true negative rate was over 98%. The quantitative results
      between the two methods were also acceptable for a screening application; Passing
      Bablok regression yielded a slope of 1.17 and a Pearson's correlation coefficient
      of 0.996. A separate PS-MS/MS negative ion screening method was also developed
      for a small panel of barbiturates and structural analogs, demonstrating its
      potential for acidic drug detection and screening.

PMID- 29377997
TI  - The importance of DNA repair for maintaining oocyte quality in response to anti
      cancer treatments, environmental toxins and maternal ageing.
AB  - BACKGROUND: Within the ovary, oocytes are stored in long-lived structures called
      primordial follicles, each comprising a meiotically arrested oocyte, surrounded
      by somatic granulosa cells. It is essential that their genetic integrity is
      maintained throughout life to ensure that high quality oocytes are available for
      ovulation. Of all the possible types of DNA damage, DNA double-strand breaks
      (DSBs) are considered to be the most severe. Recent studies have shown that DNA
      DSBs can accumulate in oocytes in primordial follicles during reproductive
      ageing, and are readily induced by exogenous factors such as gamma-irradiation,
      chemotherapy and environmental toxicants. DSBs can induce oocyte death or,
      alternatively, activate a program of DNA repair in order to restore genetic
      integrity and promote survival. The repair of DSBs has been intensively studied
      in the context of meiotic recombination, and in recent years more detail is
      becoming available regarding the repair capabilities of primordial follicle
      oocytes. OBJECTIVE AND RATIONALE: This review discusses the induction and repair
      of DNA DSBs in primordial follicle oocytes. SEARCH METHODS: PubMed (Medline) and
      Google Scholar searches were performed using the key words: primordial follicle
      oocyte, DNA repair, double-strand break, DNA damage, chemotherapy, radiotherapy,
      ageing, environmental toxicant. The literature was restricted to papers in the
      English language and limited to reports in animals and humans dated from 1964
      until 2017. The references within these articles were also manually searched.
      OUTCOMES: Recent experiments in animal models and humans have provided compelling
      evidence that primordial follicle oocytes can efficiently repair DNA DSBs arising
      from diverse origins, but this capacity may decline with increasing age. WIDER
      IMPLICATIONS: Primordial follicle oocytes are vulnerable to DNA DSBs emanating
      from endogenous and exogenous sources. The ability to repair this damage is
      essential for female fertility. In the long term, augmenting DNA repair in
      primordial follicle oocytes has implications for the development of novel
      fertility preservation agents for female cancer patients and for the management
      of maternal ageing. However, further work is required to fully characterize the
      specific proteins involved and to develop strategies to bolster their activity.

PMID- 29377998
TI  - Exploring colistin pharmacodynamics against Klebsiella pneumoniae: a need to
      revise current susceptibility breakpoints.
AB  - Objectives: Because the pharmacokinetic/pharmacodynamic (PK/PD) characteristics
      of colistin against Enterobacteriaceae are not well explored, we studied the
      activity of colistin against K. pneumoniae in an in vitro PK/PD model simulating
      different dosing regimens. Methods: Three clinical isolates of K. pneumoniae with
      MICs of 0.5, 1 and 4 mg/L were tested in an in vitro PK/PD model following a dose
      fractionation design over a period of 24 h. A high and low inoculum of 107 and
      104 cfu/mL with and without a heteroresistant subpopulation, respectively, were
      used. PK/PD indices associated with colistin activity were explored and Monte
      Carlo analysis was performed in order to determine the PTA for achieving a
      bactericidal effect (2 log kill). Results: The fAUC/MIC (R2 = 0.64-0.68) followed
      by fCmax/MIC (R2 = 0.55-0.63) best described colistin's 24 h log10 cfu/mL
      reduction for both low and high inocula. Dosing regimens with fCmax/MIC >=6 were
      always associated with a bactericidal effect (P = 0.0025). However, at clinically
      achievable concentrations, usually below fCmax/MIC = 6, an fAUC/MIC >=25 was more
      predictive of a bactericidal effect. Using a dosing regimen of 9 MU/day, the PTA
      for this pharmacodynamic target was 100%, 5%-70% and 0%, for isolates with MICs
      of <=0.5, 1 and >=2 mg/L, respectively. Dosing regimens that aim for a trough
      level of 1 mg/L achieve coverage of strains up to 0.5 mg/L (target trough/MIC = 2
      mg/L). Conclusions: Characterization of the pharmacodynamics of colistin against
      Enterobacteriaceae in an in vitro model of infection indicates that a revision of
      current susceptibility breakpoints is needed. Therapeutic drug monitoring of
      colistin to achieve pharmacodynamic targets in individual patients is highly
      recommended.

PMID- 29377999
TI  - Spot auto-focusing and spot auto-stigmation methods with high-definition auto
      correlation function in high-resolution TEM.
AB  - As alternatives to the diffractogram-based method in high-resolution transmission
      electron microscopy, a spot auto-focusing (AF) method and a spot auto-stigmation
      (AS) method are presented with a unique high-definition auto-correlation function
      (HD-ACF). The HD-ACF clearly resolves the ACF central peak region in small
      amorphous-thin-film images, reflecting the phase contrast transfer function. At a
      300-k magnification for a 120-kV transmission electron microscope, the smallest
      areas used are 64 * 64 pixels (~3 nm2) for the AF and 256 * 256 pixels for the
      AS. A useful advantage of these methods is that the AF function has an allowable
      accuracy even for a low s/n (~1.0) image. A reference database on the defocus
      dependency of the HD-ACF by the pre-acquisition of through-focus amorphous-thin
      film images must be prepared to use these methods. This can be very beneficial
      because the specimens are not limited to approximations of weak phase objects but
      can be extended to objects outside such approximations.

PMID- 29378001
TI  - Erratum to "Analysis of Postoperative Recurrence in Stage I-III Midgut
      Neuroendocrine Tumors".

PMID- 29378000
TI  - Effect of individual SCFA on the epithelial barrier of sheep rumen under
      physiological and acidotic luminal pH conditions.
AB  - The objective of this study was to investigate whether individual short-chain
      fatty acids (SCFA) have a different potential to either regulate the formation of
      the ruminal epithelial barrier (REB) at physiological pH or to damage the REB at
      acidotic ruminal pH. Ruminal epithelia of sheep were incubated in Ussing chambers
      on their mucosal side in buffered solutions (pH 6.1 or 5.1) containing no SCFA
      (control), 30 mM of either acetate, propionate or butyrate, or 100 mM acetate.
      Epithelial conductance (Gt), short-circuit current (Isc), and fluorescein flux
      rates were measured over 7 h. Thereafter, mRNA and protein abundance, as well as
      localization of the tight junction proteins claudin (Cldn)-1, -4, -7, and
      occludin were analyzed. At pH 6.1, butyrate increased Gt and decreased Isc, with
      additional decreases in claudin-7 mRNA and protein abundance (each P < 0.05) and
      disappearance of Cldn-7 immunosignals from the stratum corneum. By contrast, the
      mRNA abundance of Cldn-1 and/or Cldn-4 were upregulated by 30 mM propionate, 30
      mM butyrate, or 100 mM acetate (P < 0.05), however, without coordinated changes
      in protein abundance. At luminal pH 5.1, neither Gt, Isc, nor TJ protein
      abundance was altered in the absence of SCFA; only fluorescein flux rates were
      slightly increased (P < 0.05) and fluorescein signals were no longer restricted
      to the stratum corneum. The presence of acetate, propionate, or butyrate at pH
      5.1 increased fluorescein flux rates and Gt, and decreased Isc (each P < 0.05).
      Protein abundance of Cldn-1 was decreased in all SCFA treatments but 30 mM
      butyrate; abundance of Cldn -4 and -7 was decreased in all SCFA treatments but 30
      mM acetate; and abundance of occludin was decreased in all SCFA treatments but 30
      mM propionate (each P < 0.05). Immunofluorescence staining of SCFA-treated
      tissues at pH 5.1 showed disappearance of Cldn-7, discontinuous pattern for Cldn
      4 and blurring of occludin and Cldn-1 signals in tight junction complexes. The
      fluorescein dye appeared to freely diffuse into deeper cell layers. The strongest
      increase in Gt and consistent decreases in the abundance and immunosignals of
      tight junction proteins were observed with 100 mM acetate at pH 5.1. We conclude
      that SCFA may contribute differently to the REB formation at luminal pH 6.1 with
      possible detrimental effects of butyrate at 30 mM concentration. At luminal pH
      5.1, all SCFA elicited REB damage with concentration appearing more critical than
      SCFA species.

PMID- 29378002
TI  - Neuroblastoma.
AB  - Neuroblastoma is one of the most common solid tumors in children and has a
      diverse clinical behavior that largely depends on the tumor biology.
      Neuroblastoma exhibits unique features, such as early age of onset, high
      frequency of metastatic disease at diagnosis in patients over 1 year of age and
      the tendency for spontaneous regression of tumors in infants. The high-risk
      tumors frequently have amplification of the MYCN oncogene as well as segmental
      chromosome alterations with poor survival. Recent advanced genomic sequencing
      technology has revealed that mutation of ALK, which is present in ~10% of primary
      tumors, often causes familial neuroblastoma with germline mutation. However, the
      frequency of gene mutations is relatively small and other aberrations, such as
      epigenetic abnormalities, have also been proposed. The risk-stratified therapy
      was introduced by the Japan Neuroblastoma Study Group (JNBSG), which is now
      moving to the Neuroblastoma Committee of Japan Children's Cancer Group (JCCG).
      Several clinical studies have facilitated the reduction of therapy for children
      with low-risk neuroblastoma disease and the significant improvement of cure rates
      for patients with intermediate-risk as well as high-risk disease. Therapy for
      patients with high-risk disease includes intensive induction chemotherapy and
      myeloablative chemotherapy, followed by the treatment of minimal residual disease
      using differentiation therapy and immunotherapy. The JCCG aims for better cures
      and long-term quality of life for children with cancer by facilitating new
      approaches targeting novel driver proteins, genetic pathways and the tumor
      microenvironment.

PMID- 29378003
TI  - Dietary tea polyphenol supplementation improved egg production performance,
      albumen quality, and magnum morphology of Hy-Line Brown hens during the late
      laying period.
AB  - The aim of this study was to investigate how dietary supplementation of tea
      polyphenols (TP) and tea catechins (TC) affect laying performance, albumen
      quality, ovomucin composition, and magnum morphology of laying hens in the late
      phase of production. Two hundred seventy Hy-Line Brown laying hens (64 wk old)
      were assigned to a basal diet (the control), the basal diet supplemented with 200
      mg/kg tea polyphenols (TP200) or 200 mg/kg tea catechins (TC200). Each treatment
      had 6 replicates with 15 hens each. The feeding trial lasted 10 wks. Over the
      course of the trial, dietary supplementation with TP200 significantly increased
      the egg production (EP) and improved the feed conversion ratio (FCR) in wk 6 to
      10 and wk 1 to 10 (P < 0.05). The albumen height and the Haugh unit (HU) of hens
      fed TP200 were higher than those of hens fed the control diet at wks 8 and 10 (P
      < 0.05). However, there were no significant differences in the albumen height and
      the HU between the TP200 and TC200 groups (P > 0.05). The SDS-PAGE analysis
      indicated that bands of the ovomucin fractions in the TP200 group had the highest
      intensity compared with those of the control and TC200 groups. Compared with the
      control, there was a significant increase in protein sulfhydryl (SH) content of
      the albumen in the TP200 group at the end of experiment, while a significant
      decrease in protein carbonyl content and protein surface hydrophobicity (P <
      0.05). There were also obvious increase in the height and width of the primary
      folds, epithelial cell height, and cilia height of the simple columnar epithelium
      in the TP200 group compared with the control and TC200 groups (P < 0.05). In
      conclusion, dietary supplementation with 200 mg/kg TP can improve performance,
      albumen quality, and magnum morphology of aged hens. In addition, TP rather than
      TC could improve the health status of the magnum for aged layers.

PMID- 29378004
TI  - Responses of body fat mobilization to isoproterenol or epinephrine challenge in
      adult cows: influence of energy level, breed, and body fatness.
AB  - The sustainability of livestock production systems facing climatic or economic
      changes is linked in part to the potential of the female ruminants to adapt to
      feeding constraints through metabolic and hormonal regulation, notably responses
      of body fat mobilization, depending on adipose tissue (AT) lipolysis. Our
      hypothesis was that these responses could change according to genotype (breed)
      and body fatness. Six fat, nonpregnant, nonlactating Charolais cows, six fat
      Holstein cows, and six lean Holstein cows were used in a 2 * 2 crossover design
      with two treatments (underfeeding or overfeeding, at 62% [low] or 128% [high] of
      maintenance energy requirements [MER], respectively) and two periods.
      Isoproterenol (ISO, a nonselective beta-adrenergic agonist) or epinephrine (EPI,
      a beta- and alpha2-adrenergic agonist) was injected (6 nmol/kg of lean mass).
      Blood samples were collected regularly from -20 to 75 min after the injection and
      then were analyzed for NEFA, glycerol, glucose, and L-lactate. Underfeeding
      greatly increased (P < 0.001) basal plasma NEFA concentrations (+467%, +264%, and
      +600% for fat Charolais, fat Holstein, and lean Holstein cows, respectively). For
      each drug, underfed cows had higher NEFA or glycerol responses to adrenergic
      challenges than overfed cows. Fat Charolais cows had higher basal plasma NEFA (P
      < 0.05) concentrations (+64.9%) than fat Holstein cows. The plasma NEFA or
      glycerol response at 5 min (P < 0.05) was higher for fat Charolais than for fat
      Holstein cows, whatever the injected drug. Basal plasma lactate concentration and
      lactate response to ISO or EPI were higher (P < 0.05) for fat Charolais cows than
      for fat Holstein cows. Fat Holstein cows had higher (P < 0.01) basal glycerol
      (+18.4%) than lean Holstein cows. This increase could be linked to the increased
      AT mass. ISO increased more lipolytic responses in fat than in lean Holstein
      cows, whereas EPI increased more these responses in lean than in fat Holstein
      cows (drug * fatness interaction), suggesting an increased antilipolytic effect
      due to alpha2-AR stimulation in fat cows. Breed had a significant effect on basal
      and stimulated fat mobilization as well as lactate concentrations, suggesting
      that the Charolais breed could be more sensitive to stress.

PMID- 29378006
TI  - Effects of timing of vaccination relative to weaning and post-weaning frequency
      of energy supplementation on growth and immunity of beef calves.
AB  - A 2 * 2 factorial design study evaluated the impact of pre- vs. post-weaning
      vaccination and different post-weaning frequency of energy supplementation (daily
      vs. 3X weekly) on growth and immunity of beef calves. At 14 d before weaning (d 
      14), 48 Angus calves (24 steers and 24 heifers; 244 +/- 33 kg; 196 +/- 20 d) were
      stratified by BW and age, and randomly assigned to receive vaccinations against
      bovine viral diarrhea virus 1a (BVDV-1a) and parainfluenza-3 (PI-3) on d -14 and
      0 (PRE) or 7 and 21 (POS), relative to weaning. Calves were weaned on d 0 and
      offered daily concentrate DM supplementation (50:50 soybean hulls and corn gluten
      feed; 71% TDN, 15% CP of DM) at 0.5% of BW for 7 d. On d 7, calves were
      stratified by vaccination scheme and assigned into 1 of 16 drylot pens (3 calves
      of same sex/pen; 4 pens/treatment). Pens were randomly assigned to receive
      similar weekly concentrate DM supplementation (1% of BW multiplied by 7 d) that
      was divided and offered daily (7X) or three times weekly (3X; Mondays,
      Wednesdays, and Fridays) from d 7 to 43. From d 0 to 43, calves were provided ad
      libitum ground tall fescue hay (57% TDN, 13% CP of DM). Blood samples were
      collected from jugular vein on d 0, 1, 3, 7, and 14, relative to the respective
      first vaccination, and on d 43 of the study. Effects of timing of vaccination *
      frequency of supplementation were not detected for any variable in this study (P
      >= 0.12), except for overall ADG from d -14 to 43 (P = 0.04), which was less for
      PRE-3X vs. PRE-7X, POS-3X, and POS-7X calves (0.60, 0.70, 0.70, and 0.77 +/- 0.04
      kg/d, respectively; P <= 0.08). Post-weaning total DMI and G:F did not differ
      among treatments (P >= 0.11). Pre-weaning vaccination increased plasma
      concentrations of cortisol and haptoglobin from d 0 to 3, relative to first
      vaccination (P <= 0.03), and decreased serum PI-3 titers on d 43 compared with
      post-weaning vaccination (P < 0.0001). Decreasing the supplementation frequency
      tended (P = 0.10) to increase overall plasma cortisol concentrations and reduce
      overall serum BVDV-1a titers. Hence, pre-weaning vaccination associated with
      reduced post-weaning frequency of energy supplementation caused the greatest
      reduction on calf growth performance. Post-weaning vaccination and daily energy
      supplementation alleviated inflammation and improved humoral immunity compared
      with pre-weaning vaccination and reduced post-weaning frequency of energy
      supplementation of recently weaned beef calves.

PMID- 29378005
TI  - Tau Oligomer Pathology in Nucleus Basalis Neurons During the Progression of
      Alzheimer Disease.
AB  - Although tau is the primary constituent of neurofibrillary tangles (NFTs),
      evidence suggests that its toxic moiety is oligomeric in Alzheimer disease (AD).
      In this regard, tau oligomers correlate more strongly with neuronal loss than
      NFTs and exhibit neurotoxicity in preclinical AD models. Here, we investigated
      the spatiotemporal progression of oligomeric tau accumulation within the highly
      vulnerable cholinergic neurons of the nucleus basalis of Meynert (nbM) in AD.
      Tissue from subjects who died with a clinical diagnosis of no cognitive
      impairment, mild cognitive impairment, or AD was immunostained with the tau
      oligomeric complex 1 (TOC1) antibody, a marker of tau oligomers, and p75NTR, a
      cholinergic cell marker. Stereological estimates revealed a significant increase
      in the number of TOC1 nbM immunopositive (+) neurons with a concomitant decrease
      in p75NTR+ nbM neurons during the transition from mild cognitive impairment to
      AD. Immunofluorescence identified TOC1+ neurons that colocalized with the
      pretangle tau marker phospho-Ser422, which persisted into late stage NFTs
      immunoreactive for MN423. Analysis of the nbM subfields revealed a topographical
      caudal to rostral gradient of TOC1+ neurons during disease progression. Taken
      together, these data suggest that toxic tau oligomers accumulate caudorostrally
      in selectively vulnerable nbM neurons during the onset of AD.

PMID- 29378007
TI  - Autophagy controls resource allocation and protein storage accumulation in
      Arabidopsis seeds.
AB  - Autophagy is essential for nutrient recycling and plays a fundamental role in
      seed production and grain filling in plants. Autophagy participates in nitrogen
      remobilization at the whole-plant level, and the seeds of autophagy mutants
      present abnormal C and N contents relative to wild-type (WT) plants. It is well
      known that autophagy (ATG) genes are induced in leaves during senescence;
      however, expression of such genes in seeds has not yet been reported. In this
      study we show that most of the ATG genes are induced during seed maturation in
      Arabidopsis siliques. Promoter-ATG8f::UIDA and promoter-ATG8f::GFP fusions showed
      the strong expression of ATG8f in the phloem companion cells of pericarps and the
      funiculus, and in the embryo. Expression was especially strong at the late stages
      of development. The presence of many GFP-ATG8 pre-autophagosomal structures and
      autophagosomes confirmed the presence of autophagic activity in WT seed embryos.
      Seeds of atg5 and WT plants grown under low- or high-nitrate conditions were
      analysed. Nitrate-independent phenotypes were found with higher seed abortion in
      atg5 and early browing, higher total protein concentrations in the viable seeds
      of this mutant as compared to the WT. The higher total protein accumulation in
      atg5 viable seeds was significant from early developmental stages onwards. In
      addition, relatively low and early accumulation of 12S globulins were found in
      atg5 seeds. These features led us to the conclusion that atg5 seed development is
      accelerated and that the protein storage deposition pathway is somehow abnormal
      or incomplete.

PMID- 29378009
TI  - Your contribution to a living journal.

PMID- 29378008
TI  - Genetic correlations between feed efficiency traits, and growth performance and
      carcass traits in purebred and crossbred pigs.
AB  - Selection for feed efficiency (FE) is a strategy to reduce the production costs
      per unit of animal product, which is one of the major objectives of current
      animal breeding programs. In pig breeding, selection for FE and other traits
      traditionally takes place based on purebred pig (PB) performance at the nucleus
      level, while pork production typically makes use of crossbred animals (CB). The
      success of this selection, therefore, depends on the genetic correlation between
      the performance of PB and CB (rpc) and on the genetic correlation (rg) between FE
      and the other traits that are currently under selection. Different traits are
      being used to account for FE, but the rpc has been reported only for feed
      conversion rate. Therefore, this study aimed 1) to estimate the rpc for growth
      performance, carcass, and FE traits; 2) to estimate rg between traits within PB
      and CB populations; and 3) to compare three different traits representing FE:
      feed conversion rate, residual energy intake (REI), and residual feed intake
      (RFI). Phenotypes of 194,445 PB animals from 23 nucleus farms, and 46,328 CB
      animals from three farms where research is conducted under near commercial
      production conditions were available for this study. From these, 22,984 PB and
      8,657 CB presented records for feed intake. The PB population consisted of five
      sire and four dam lines, and the CB population consisted of terminal cross
      progeny generated by crossing sires from one of the five PB sire lines with
      commercially available two-way maternal sow crosses. Estimates of rpc ranged from
      0.61 to 0.71 for growth performance traits, from 0.75 to 0.82 for carcass traits,
      and from 0.62 to 0.67 for FE traits. Estimates of rg between growth performance,
      carcass, and FE traits differed within PB and CB. REI and RFI showed substantial
      positive rg estimates in PB (0.84) and CB (0.90) populations. The magnitudes of
      rpc estimates indicate that genetic progress is being realized in CB at the
      production level from selection on PB performance at nucleus level. However,
      including CB phenotypes recorded on production farms, when predicting breeding
      values, has the potential to increase genetic progress for these traits in CB.
      Given the genetic correlations with growth performance traits and the genetic
      correlation between the performance of PB and CB, REI is an attractive FE
      parameter for a breeding program.

PMID- 29378010
TI  - Genetic Influences on the Development of Cerebral Cortical Thickness During
      Childhood and Adolescence in a Dutch Longitudinal Twin Sample: The Brainscale
      Study.
AB  - Previous studies have demonstrated that cortical thickness (CT) is under strong
      genetic control across the life span. However, little is known about genetic
      influences that cause changes in cortical thickness (DeltaCT) during brain
      development. We obtained 482 longitudinal MRI scans at ages 9, 12, and 17 years
      from 215 twins and applied structural equation modeling to estimate genetic
      influences on (1) cortical thickness between regions and across time, and (2)
      changes in cortical thickness between ages. Although cortical thickness is
      largely mediated by the same genetic factor throughout late childhood and
      adolescence, we found evidence for influences of distinct genetic factors on
      regions across space and time. In addition, we found genetic influences for
      cortical thinning during adolescence that is mostly due to fluctuating influences
      from the same genetic factor, with evidence of local influences from a second
      emerging genetic factor. This fluctuating core genetic factor and emerging novel
      genetic factor might be implicated in the rapid cognitive and behavioral
      development during childhood and adolescence, and could potentially be targets
      for investigation into the manifestation of psychiatric disorders that have their
      origin in childhood and adolescence.

PMID- 29378011
TI  - Effects of supplementing sow diets with fermented corn and soybean meal mixed
      feed during lactation on the performance of sows and progeny.
AB  - In the present study, two experiments were performed to study the effects of
      feeding fermented corn and soybean meal mixed feed (FMF) with Bacillus subtilis
      and Enterococcus faecium to lactating sows on the performance of the sows and
      their progeny. In experiment 1, 60 sows were allocated to the following three
      dietary treatments: 1) sows fed a corn and soybean meal basal diet (control) from
      day 3 before parturition to weaning, 2) sows fed a diet with 7.5% FMF, and 3)
      sows fed a diet with 15% FMF. Results indicated that feeding 15% FMF
      significantly improved (P < 0.05) the sows' ADFI, the individual piglet weaning
      weights, and piglet weight gain and reduced (P < 0.05) the backfat loss of sows
      compared with the control group. However, the 7.5% FMF treatment did not alter
      the performance of the sows or their progeny. Therefore, we considered the level
      of 15% FMF to be more efficient than 7.5% FMF. To verify the results of
      experiment 1, we performed experiment 2, in which 60 sows at 111 d of gestation
      were allocated into the following two dietary treatments: 1) sows fed a basal
      lactation diet (control) from d 111 of gestation to weaning and 2) sows fed a
      basal diet with 15% FMF. Compared with the control group, 15% FMF inclusion
      significantly increased (P < 0.05) the sows' ADFI, litter weight gain, and
      individual piglet weight gain during lactation and markedly decreased the backfat
      loss of sows (P < 0.05) and piglet diarrhea incidence (P < 0.05). Additionally,
      the milk yield and IgA contents of the milk in sows fed 15% FMF were greater (P <
      0.05) than those of the control group. Furthermore, the apparent total tract
      digestibility of GE, DM, and total P of sows was increased (P < 0.05) with 15%
      FMF supplementation. Therefore, the present study indicates that supplementing
      sow diets with 15% FMF from parturition to weaning has the potential to 1)
      increase sow ADFI, milk production, milk IgA content, and nutrient digestibility
      and promote sow reproductive performance by shortening the weaning-to-estrous
      interval and 2) promote the growth performance of their progeny and decrease
      diarrhea incidence.

PMID- 29378012
TI  - i-Motif of cytosine-rich human telomere DNA fragments containing natural base
      lesions.
AB  - i-Motif (iM) is a four stranded DNA structure formed by cytosine-rich sequences,
      which are often present in functionally important parts of the genome such as
      promoters of genes and telomeres. Using electronic circular dichroism and UV
      absorption spectroscopies and electrophoretic methods, we examined the effect of
      four naturally occurring DNA base lesions on the folding and stability of the iM
      formed by the human telomere DNA sequence (C3TAA)3C3T. The results demonstrate
      that the TAA loop lesions, the apurinic site and 8-oxoadenine substituting for
      adenine, and the 5-hydroxymethyluracil substituting for thymine only marginally
      disturb the formation of iM. The presence of uracil, which is formed by enzymatic
      or spontaneous deamination of cytosine, shifts iM formation towards substantially
      more acidic pH values and simultaneously distinctly reduces iM stability. This
      effect depends on the position of the damage sites in the sequence. The results
      have enabled us to formulate additional rules for iM formation.

PMID- 29378014
TI  - The delayed southern migration of a transcatheter aortic valve.
AB  - Transcatheter aortic valve replacement has emerged as a favourable alternative in
      patients with severe symptomatic aortic stenosis who are at intermediate and/or
      high risk for open aortic valve replacement. While transcatheter aortic valve
      replacement has been shown to be a safe alternative to surgical aortic valve
      replacement in those populations, the procedure is not without risks.
      Transcatheter heart valve migration can occur, albeit rarely, in an acute,
      subacute and delayed fashion. This complication can have fatal consequences if
      not managed appropriately. We describe a patient who underwent a transcatheter
      aortic valve replacement and had evidence of transcatheter heart valve subacute
      migration into the left ventricular outflow tract.

PMID- 29378013
TI  - A conserved structural element in the RNA helicase UPF1 regulates its catalytic
      activity in an isoform-specific manner.
AB  - The RNA helicase UPF1 is a key component of the nonsense mediated mRNA decay
      (NMD) pathway. Previous X-ray crystal structures of UPF1 elucidated the molecular
      mechanisms of its catalytic activity and regulation. In this study, we examine
      features of the UPF1 core and identify a structural element that adopts different
      conformations in the various nucleotide- and RNA-bound states of UPF1. We
      demonstrate, using biochemical and single molecule assays, that this structural
      element modulates UPF1 catalytic activity and thereby refer to it as the
      regulatory loop. Interestingly, there are two alternatively spliced isoforms of
      UPF1 in mammals which differ only in the lengths of their regulatory loops. The
      loop in isoform 1 (UPF11) is 11 residues longer than that of isoform 2. We find
      that this small insertion in UPF11 leads to a two-fold increase in its
      translocation and ATPase activities. To determine the mechanistic basis of this
      differential catalytic activity, we have determined the X-ray crystal structure
      of the helicase core of UPF11 in its apo-state. Our results point toward a novel
      mechanism of regulation of RNA helicases, wherein alternative splicing leads to
      subtle structural rearrangements within the protein that are critical to modulate
      enzyme movements and catalytic activity.

PMID- 29378015
TI  - DETERMINATION OF THE RESPONSE TO THE ATMOSPHERIC COSMIC RADIATION OF A NEUTRON
      DOSIMETER ASSISTED BY MONTE CARLO SIMULATION.
AB  - A TLD-based dosimeter of polyethylene-lead-polyethylene, was developed and
      characterized with Monte Carlo simulations, using the MCNPX code. This passive
      system for the determination of the ambient dose equivalent (H*(10)) for neutrons
      over a wide energy range can be used for the dosimetry of neutrons from
      atmospheric cosmic radiation, on the ground, and onboard aircraft. A method
      assisted by Monte Carlo simulations that improves the calibration of fast neutron
      dosimeters based on moderation and thermalization of the incident fast flux and
      the measurement of the thermal flux by a sensor, which respond mainly to thermal
      neutrons, is presented in this work. The H*(10) energy response of this dosimeter
      was obtained from simulations for monoenergetic neutrons from 10-10 to 104 MeV.
      The validation of the modeling was done with irradiations for ISO standard
      neutron fields of 241Am-Be, 252Cf and 252Cf(D2O) at Instituto de Radioprotecao e
      Dosimetria (IRD, Brazil) and at CERN-EU high-energy reference field (CERF).

PMID- 29378016
TI  - A Phase I, Randomized, Double-Blind, Laser-Evoked Potential Study to Evaluate the
      Analgesic/Antihyperalgesic Effect of ASP9226, a State-Dependent N-Type Voltage
      Gated Calcium Channel Inhibitor, in Healthy Male Subjects.
AB  - Objective: Evaluate the analgesic/antihyperalgesic effects of ASP9226, a state
      dependent N-type voltage-gated calcium channel inhibitor, in healthy male
      subjects. Design: Randomized, double-blind, double-dummy, placebo- and active
      comparator-controlled crossover study. Setting: HPR Dr. Schaffler GmbH, Munich,
      Germany. Subject: Healthy male subjects aged 18-55 years. Methods: Twenty-four
      eligible subjects were randomly assigned to one of four treatment sequences and
      received single doses of ASP9226 (30 mg or 50 mg), pregabalin (150 mg), or
      placebo during four treatment periods. Laser-evoked potentials (LEP) and
      postlaser pain visual analog scales (VAS) on capsaicin-treated skin were assessed
      during main assessment days (the first day of each study period). Primary and
      secondary end points were the differences in LEP N2-P2 peak-to-peak (PtP)
      amplitudes and VAS score, respectively, in all subjects. Results: Overall,
      treatment with pregabalin resulted in a significantly lower LEP N2-P2 PtP
      amplitude vs placebo (-3.30 MUV, P < 0.0001). There were no clinically relevant
      differences in N2-P2 PtP amplitudes between placebo and either ASP9226 dose (
      0.31 MUV and -0.27 MUV). Furthermore, subjects reported significantly lower VAS
      pain scores with pregabalin vs placebo (-9.90%, P < 0.0001) in contrast to
      ASP9226 30 mg (-2.1%) and ASP9226 50 mg (1.2%) vs placebo. Subgroup analysis of
      LEP and VAS pain in participants with positive prestudy capsaicin response (n =
      13) were in keeping with results in all subjects. Conclusions: ASP9226 was well
      tolerated; however, there was no improvement in LEP and VAS pain scores with
      ASP9226 at either dose vs placebo.

PMID- 29378017
TI  - Plasma Activation of a Breast Implant Shell in Conjunction With Antibacterial
      Irrigants Enhances Antibacterial Activity.
AB  - Background: Infection and capsular contracture are two of the most significant
      complications of breast-implant surgery. Both complications are associated with
      bacterial contamination of the implant surface. Plasma activation of the surface
      of a silicone breast implant changes its surface properties from water repelling
      (hydrophobic) to water absorbing (hydrophilic), thus making it possible for
      antibacterial irrigants to temporarily adsorb onto the implant surface.
      Objectives: To support our hypothesis that by changing the surface properties we
      could render antibacterial irrigation more effective in inhibiting bacterial
      growth on a breast implant shell. Methods: An in vitro study using silicone discs
      cut from a textured silicone breast implant shell was performed by treating some
      of the discs with plasma activation and then exposing the discs to contamination
      with either Staphylococcus aureus or Pseudomonas aeruginosa and then variously
      treating the discs with 10% povidone iodine, Cefazolin, or Gentamicin. Bacterial
      contamination was verified and counted using contact plates as well as culture
      media. Results: Plasma activation changed the wetting properties of the disc's
      surface from hydrophobic to hydrophilic. Nonplasma activated contaminated discs
      demonstrated clear bacterial growth both in the untreated group and in the
      antibacterial-treated group. Combining antibacterial treatment with plasma
      activation resulted in complete inhibition of bacterial growth in each of the
      groups treated with antibacterial irrigants. Conclusions: Combining plasma
      activation with topical antibacterial irrigants can inhibit the growth of
      bacteria on implant shell discs. By changing the properties of the surface from
      hydrophobic to hydrophilic, the adsorption of the antibacterial irrigants is
      enhanced.

PMID- 29378018
TI  - Beliefs About Suicide Acceptability in the United States: How Do They Affect
      Suicide Mortality?
AB  - Objectives: Societies develop cultural scripts to understand suicide and define
      conditions under which the act is acceptable. Prior empirical work suggests that
      such attitudes are important in understanding some forms of suicidal behavior
      among adolescents and high-risk populations. This study examines whether
      expressions of suicide acceptability under different circumstances are predictive
      of subsequent death by suicide in the general U.S. adult population and whether
      the effects differ over the life course. Method: The study uses 1978-2010 General
      Social Survey data linked to the National Death Index through 2014 (n = 31,838).
      Cox survival models identify risk factors for suicide mortality, including
      attitudinal and cohort effects. Results: Expressions of suicide acceptability are
      predictive of subsequent death by suicide-in some cases associated with a twofold
      increase in risk. Attitudes elevate the suicide hazard among older (>55 years)
      adults but not among younger (ages 33-54) adults. Fully-adjusted models reveal
      that the effects of attitudes toward suicide acceptability on suicide mortality
      are strongest for social circumstances (family dishonor; bankruptcy). Discussion:
      Results point to the role of cultural factors and social attitudes in suicide.
      There may be utility in measuring attitudes in assessments of suicide risk.

PMID- 29378019
TI  - The Cardiomyopathy Registry of the EURObservational Research Programme of the
      European Society of Cardiology: baseline data and contemporary management of
      adult patients with cardiomyopathies.
AB  - Aims: The Cardiomyopathy Registry of the EURObservational Research Programme is a
      prospective, observational, and multinational registry of consecutive patients
      with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated
      cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and
      restrictive cardiomyopathy (RCM). We report the baseline characteristics and
      management of adults enrolled in the registry. Methods and results: A total of
      3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n
      = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy
      subtypes (P < 0.001) were observed for age at diagnosis, history of familial
      disease, history of sustained ventricular arrhythmia, use of magnetic resonance
      imaging or genetic testing, and implantation of defibrillators. When compared
      with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar
      rate of symptoms and defibrillators. When compared with the Long-Term phase,
      patients of the Pilot phase (enrolled in more expert centres) had a more frequent
      rate of familial disease (P < 0.001), were more frequently diagnosed with a rare
      underlying disease (P < 0.001), and more frequently implanted with a
      defibrillator (P = 0.023). Comparing four geographical areas, patients from
      Southern Europe had a familial disease more frequently (P < 0.001), were more
      frequently diagnosed in the context of a family screening (P < 0.001), and more
      frequently diagnosed with a rare underlying disease (P < 0.001). Conclusion: By
      providing contemporary observational data on characteristics and management of
      patients with cardiomyopathies, the registry provides a platform for the
      evaluation of guideline implementation. Potential gaps with existing
      recommendations are discussed as well as some suggestions for improvement of
      health care provision in Europe.

PMID- 29378021
TI  - Localized gene expression changes during adventitious root formation in black
      walnut (Juglans nigra L.).
AB  - Cutting propagation plays a large role in the forestry and horticulture
      industries where superior genotypes need to be clonally multiplied. Integral to
      this process is the ability of cuttings to form adventitious roots. Recalcitrance
      to adventitious root development is a serious hurdle for many woody plant
      propagation systems including black walnut (Juglans nigra L.), an economically
      valuable species. The inability of black walnut to reliably form adventitious
      roots limits propagation of superior genotypes. Adventitious roots originate from
      different locations, and root induction is controlled by many environmental and
      endogenous factors. At the molecular level, however, the regulation of
      adventitious root formation is still poorly understood. In order to elucidate the
      transcriptional changes during adventitious root development in black walnut, we
      used quantitative real-time polymerase chain reaction to measure the expression
      of nine key genes regulating root formation in other species. Using our
      previously developed spatially explicit timeline of adventitious root development
      in black walnut softwood cuttings, we optimized a laser capture microdissection
      protocol to isolate RNA from cortical, phloem fiber and phloem parenchyma cells
      throughout adventitious root formation. Laser capture microdissection permitted
      high-resolution, site-specific analysis of gene expression that differentiated
      between participatory and non-participatory root progenitor cells. Results
      indicated mRNA abundance was altered in all nine rooting-related genes in
      response to auxin treatment in both juvenile and mature cuttings. SCARECROW LIKE
      1 (SCL) had the greatest change in expression in juvenile rooting-competent cells
      at days 16 and 18, with a 24- and 23-fold increase relative to day 0,
      respectively. Tissues not linked to root organogenesis had little change in SCL
      expression at similar time points. AUXIN RESPONSE FACTOR (ARF)6 and ARF8 as well
      as SHORTROOT expression also increased 2- to 4-fold in rooting-competent tissue.
      The greatest transcript abundance in rooting-competent cuttings was restricted to
      root progenitor cells, while recalcitrant cuttings had a diffuse mRNA signal
      among tissue types.

PMID- 29378020
TI  - Multiple Roots of Fruiting Body Formation in Amoebozoa.
AB  - Establishment of multicellularity represents a major transition in eukaryote
      evolution. A subgroup of Amoebozoa, the dictyosteliids, has evolved a relatively
      simple aggregative multicellular stage resulting in a fruiting body supported by
      a stalk. Protosteloid amoeba, which are scattered throughout the amoebozoan tree,
      differ by producing only one or few single stalked spores. Thus, one obvious
      difference in the developmental cycle of protosteliids and dictyosteliids seems
      to be the establishment of multicellularity. To separate spore development from
      multicellular interactions, we compared the genome and transcriptome of a
      Protostelium species (Protostelium aurantium var. fungivorum) with those of
      social and solitary members of the Amoebozoa. During fruiting body formation
      nearly 4,000 genes, corresponding to specific pathways required for
      differentiation processes, are upregulated. A comparison with genes involved in
      the development of dictyosteliids revealed conservation of >500 genes, but most
      of them are also present in Acanthamoeba castellanii for which fruiting bodies
      have not been documented. Moreover, expression regulation of those genes differs
      between P. aurantium and Dictyostelium discoideum. Within Amoebozoa
      differentiation to fruiting bodies is common, but our current genome analysis
      suggests that protosteliids and dictyosteliids used different routes to achieve
      this. Most remarkable is both the large repertoire and diversity between species
      in genes that mediate environmental sensing and signal processing. This likely
      reflects an immense adaptability of the single cell stage to varying
      environmental conditions. We surmise that this signaling repertoire provided
      sufficient building blocks to accommodate the relatively simple demands for cell
      cell communication in the early multicellular forms.

PMID- 29378023
TI  - The Bidirectional Relationship Between Depressive Symptoms and Homebound Status
      Among Older Adults.
AB  - Objectives: This study aimed to examine the bidirectional relationship between
      depressive symptoms and homebound status among older adults. Method: The study
      sample included 7,603 community-dwelling older adults from the National Health
      and Aging Trends Study. A bivariate latent state-trait model of depressive
      symptoms and homebound status was estimated via structural equation modeling.
      Results: The model fit the data well (Root Mean Square Error of Approximation =
      .02, Comparative Fit Index = .97, Standardized Root Mean Square Residual = .06).
      The relationship between homebound status and depressive symptoms can be
      decomposed into three parts: a moderate correlation between the stable trait
      components (r = .56, p <.001); a contemporary association of the state components
      (b = .17, p <.001); and bidirectional lagged effects between the state
      components. Change in homebound status was as a stronger predictor of depressive
      symptoms (b = .19, p < .001) than change in depressive symptoms was of homebound
      status (b = .06, p < .001; test of difference: Delta scaled chi2(1) = 24.2, p <
      .001). Discussion: Homebound status and depressive symptoms form a feedback loop
      to influence each other. Improving the outdoor mobility of older adults may have
      immediate benefits for reducing depressive symptoms.

PMID- 29378022
TI  - The interaction between embodiment and empathy in facial expression recognition.
AB  - Previous research has demonstrated that the Action-Observation Network (AON) is
      involved in both emotional-embodiment (empathy) and action-embodiment mechanisms.
      In this study, we hypothesized that interfering with the AON will impair action
      recognition and that this impairment will be modulated by empathy levels. In
      Experiment 1 (n = 90), participants were asked to recognize facial expressions
      while their facial motion was restricted. In Experiment 2 (n = 50), we interfered
      with the AON by applying transcranial Direct Current Stimulation to the motor
      cortex. In both experiments, we found that interfering with the AON impaired the
      performance of participants with high empathy levels; however, for the first
      time, we demonstrated that the interference enhanced the performance of
      participants with low empathy. This novel finding suggests that the embodiment
      module may be flexible, and that it can be enhanced in individuals with low
      empathy by simple manipulation of motor activation.

PMID- 29378025
TI  - Plant Cuttings: news in Botany.

PMID- 29378024
TI  - Impact of a commercially available model-based dose calculation algorithm on
      treatment planning of high-dose-rate brachytherapy in patients with cervical
      cancer.
AB  - We evaluated the impact of model-based dose calculation algorithms (MBDCAs) on
      high-dose-rate brachytherapy (HDR-BT) treatment planning for patients with
      cervical cancer. Seven patients with cervical cancer treated using HDR-BT were
      studied. Tandem and ovoid applicators were used in four patients, a vaginal
      cylinder in one, and interstitial needles in the remaining two patients. MBDCAs
      were applied to the Advanced Collapsed cone Engine (ACE; Elekta, Stockholm,
      Sweden). All plans, which were originally calculated using TG-43, were re
      calculated using both ACE and Monte Carlo (MC) simulations. Air was used as the
      rectal material. The mean difference in the rectum D2cm3 between ACErec-air and
      MCrec-air was 8.60 +/- 4.64%, whereas that in the bladder D2cm3 was -2.80 +/-
      1.21%. Conversely, in the small group analysis (n = 4) using water instead of air
      as the rectal material, the mean difference in the rectum D2cm3 between TG-43 and
      ACErec-air was 11.87 +/- 2.65%, whereas that between TG-43 and ACErec-water was
      0.81 +/- 2.04%, indicating that the use of water as the rectal material reduced
      the difference in D2cm3 between TG-43 and ACE. Our results suggested that the
      differences in the dose-volume histogram (DVH) parameters of TG-43 and ACE were
      large for the rectum when considerable air (gas) volume was present in it, and
      that this difference was reduced when the air (gas) volume was reduced. Also, ACE
      exhibited better dose calculation accuracy than that of TG-43 in this situation.
      Thus, ACE may be able to calculate the dose more accurately than TG-43 for HDR-BT
      in treating cervical cancers, particularly for patients with considerable air
      (gas) volume in the rectum.

PMID- 29378026
TI  - Individual stability in vocalization rates of preweaning piglets.
AB  - Piglet vocalization rates are used as welfare indicators. The emission rates of
      the two gross categories of piglet calls, namely low frequency calls ("grunts")
      and high frequency calls ("screams"), may contain different information about the
      piglet's internal state due to differing communicative functions of the two call
      types. More knowledge is needed about the sources of variation in calling rates
      within and between piglets. We examined to what extent the emission rates of the
      two call types are codetermined by individual and litter identity, i.e., whether
      the rates are repeatable within individuals and similar between littermates. We
      recorded frequency of grunts and screams in one mildly negative (short-term
      Isolation) and one moderately negative (manual Restraint) situation during the
      first week (week 1) and the 4th week (week 4) of life and asked the following
      questions: 1) Are within-individual vocalization rates stable across the suckling
      period? 2) Are within-individual vocalization rates stable across the two
      situations? 3) Is there within-litter similarity in vocalization rates? 4) Does
      this within-litter similarity increase during the suckling period? Within
      individual vocalization rates were stable between week 1 and week 4 (grunts in
      Restraint P < 0.05; grunts in Isolation P < 0.001; screams in Restraint P <
      0.001; screams in Isolation P < 0.001). Across the two situations at the same
      age, the vocalization rates were not stable for grunts but were stable for
      screams at week 1 and week 4 (P < 0.05). Vocalization rates were more similar
      between littermates than between piglets belonging to different litters (grunts
      in Restraint P < 0.001; grunts in Isolation P < 0.01; screams in Restraint P <
      0.001; screams in Isolation P < 0.001). This litter effect did not grow stronger
      from week 1 to week 4 as the within-litter coefficient of variance did not
      decrease between the two ages. Sex of the piglet had no influence on vocalization
      rates while greater body weight was associated with lower screaming rates in the
      Restraint situation (P < 0.05). In conclusion, our study demonstrates that both
      individuality of the piglet and litter identity affect the vocalization rates of
      piglets in negatively valenced situations. For screams, the repeatability of
      individual vocalization rates holds even across situations, while for grunts, the
      rates are repeatable during ontogeny within the situations, but not across
      situations.

PMID- 29378027
TI  - Phosphine Analysis in Postmortem Specimens Following Inhalation of Phosphine:
      Fatal Aluminum Phosphide Poisoning in Children.
AB  - Phosphine is an insecticide for the fumigation of grains, animal feed, and leaf
      stored tobacco, and it was used as a rodenticide in bulk grain stores. Phosphine
      poisoning may occur after accidental inhalation of phosphine, sometimes leading
      to death. Analysis of phosphine and its metabolites in postmortem specimens from
      seven fatal cases was conducted in this study, as well as postmortem specimens
      collected from rabbits exposed to phosphine. The total phosphine in postmortem
      specimens was analyzed by headspace gas chromatography coupled with mass
      spectrometry. Diagnosis of aluminum phosphide poisoning was made after postmortem
      toxicological analysis and confirmed by police investigation. The deaths of the
      children occurred after inhalation of phosphine generated from aluminum phosphide
      contacting moisture in the air in all seven fatal cases. The concentration of
      total phosphine in the biological fluids and tissues of victims ranged from 0.2
      to 4.7 MUg/mL (MUg/g). Animal experiments demonstrated that the phosphine
      generated from aluminum phosphide could rapidly cause death. The toxicological
      analysis of postmortem specimens provides useful information in diagnosis of
      aluminum phosphide poisoning in forensic science. As an important fumigation
      pesticide, aluminum phosphide deserves special attention, especially since there
      is no specific antidote and there is a high fatality rate.

PMID- 29378028
TI  - Patient Satisfaction as a Moderator of Risky Alcohol Consumers' Attitude Towards
      Screening and Brief Intervention: A Cross Sectional Survey.
AB  - Aims: Although shown to be effective, General Practitioners (GPs) tend to refuse
      the implementation of Screening and Brief Intervention (SBI). Their expectation
      of negative response by patients seems to contrast with the positive attitude
      towards SBI of these patients. This discrepancy may be resolved by regarding
      moderators such as drinking status and patient satisfaction. We hypothesized that
      the attitude towards SBI will be more positive for abstainers or low-level
      consumers in comparison to high risk consumers especially in case of low patient
      satisfaction. Methods: Ten GP offices in Germany received the questionnaires for
      a recruitment maximum of 30 patients each. Patient satisfaction was measured by
      the Koelner Questionnaire of Patient Satisfaction and drinking status was
      evaluated using the AUDIT-C. To assess the SBI attitude a pretested 8-item Likert
      scale was used. Results: Questionnaires of 257 patients could be analyzed. Almost
      a third of patients were risky consumers (N = 78, 29.9%). They showed a more
      negative attitude towards SBI (M = 3.99, SD = 0.71) than abstainers or low-level
      consumers (M = 4.20, SD = 0.55). The main analysis revealed main effects for
      alcohol consumption, F(1, 252) = 4.31, P < 0.05, and patient satisfaction, F(1,
      252) = 22.15, P < 0.001, as well as an interaction effect, F(1, 252) = 5.01, P <
      0.05, showing that the SBI attitude of risky consumers was more negative than the
      SBI attitude of abstainers or low-level consumers only in case of low
      satisfaction. Conclusions: Risky consumers show a more positive attitude towards
      SBI when they are satisfied with their GP. Our results thus suggest the use of a
      supportive consultation style for the intervention of risky consumers. Short
      Summary: SBI attitude of general practice patients depends on their drinking
      status: abstainers or low-level consumers revealed a more positive attitude
      towards SBI than risky consumers. This effect is moderated by the patient's
      satisfaction. Risky consumers show a more positive attitude towards SBI if they
      are satisfied with their GP.

PMID- 29378029
TI  - Porcine epidemic diarrhea virus reduces feed efficiency in nursery pigs.
AB  - Porcine epidemic diarrhea virus (PEDV) infects enterocytes and in nursery pigs,
      results in diarrhea, anorexia, and reduced performance. Therefore, the objective
      of this study was to determine how PEDV infection influenced growth performance
      and repartitioning of amino acids and energy in nursery pigs. A total of 32
      barrows and gilts, approximately 1 wk post-wean (BW = 8.46 +/- 0.50 kg), and
      naive for PEDV were obtained, weighed, and allotted based on sex and BW to one of
      two treatments: 1) Control, PEDV naive and 2) PEDV-inoculated (PEDV) with eight
      pens of two pigs each per treatment. On day post-inoculation (dpi) 0, PEDV pigs
      were inoculated via intragastric gavage with PEDV isolate (USA/Iowa/18984/2013).
      Pig and feeder weights were recorded at dpi -7, 0, 5, and 20 in order to
      calculate ADG, ADFI, and G:F. Eight pigs per treatment were euthanized on dpi 5
      and 20, and tissues and blood were collected. At dpi 5, all PEDV pigs were PCR
      positive for PEDV in feces. Overall, PEDV pigs tended (P < 0.10) to increase
      ADFI, which resulted in reduced (P < 0.05) feed efficiency. At dpi 5, PEDV pigs
      had reduced (P < 0.05) villus height and increased (P < 0.05) stem cell
      proliferation in the jejunum compared with Control pigs. Pigs inoculated with
      PEDV had increased (P < 0.05) serum haptoglobin and increased insulin-to-glucose
      ratios compared with Control pigs at dpi 5. Markers of muscle proteolysis were
      not different (P > 0.05) between treatments within dpi; however, at dpi 5, 20S
      proteasome activity was increased (P < 0.05) in longissimus dorsi of PEDV pigs
      compared with Control pigs. Liver and jejunum gluconeogenic enzyme activities
      were not different (P > 0.05) between treatments within dpi. Overall, PEDV
      inoculated pigs did recover the absorptive capacity that was reduced during PEDV
      infection by increasing proliferation of intestinal stem cells. However, the
      energy and nutrients needed to recover the epithelium may be originating from
      available luminal nutrients instead of muscle proteolysis and gluconeogenesis.
      This study provides insight into the effects of an enteric coronavirus on
      postabsorptive metabolism in nursery pigs.

PMID- 29378030
TI  - Inducible Costimulator Contributes to Methicillin-Resistant Staphylococcus aureus
      Pneumonia.
AB  - Staphylococcus aureus is a major cause of both community- and healthcare-acquired
      pneumonias. Inducible costimulator (ICOS) is part of the CD28 family of proteins
      and is a target for immune checkpoint therapy. We found ICOS highly expressed on
      activated CD4 cells in response to S. aureus. In the absence of ICOS, mice had
      improved survival in a pneumonia model with the methicillin-resistant
      Staphylococcus aureus (MRSA) strain USA300 and significant reductions in
      bacterial burden in a nonlethal acute pneumonia model. Infected Icos-/- mice had
      major reductions in several proinflammatory cytokines, neutrophils, inflammatory
      monocytes, and eosinophils compared to infected wild-type mice, while there was
      improved expression of CD11c and macrophage receptor with collagenous structure
      on the surface of alveolar macrophages. Early during infection infected Icos-/-
      mice had increased numbers of alveolar macrophages and expression of several
      surface markers on alveolar macrophages and neutrophils. ICOS signaling also
      contributed to the pathogenesis of the airway pathogens Klebsiella pneumoniae,
      Pseudomonas aeruginosa, and Streptococcus pneumoniae, and neutralizing antibody
      to ICOS led to improved clearance of S. aureus from the airway. Our results
      indicate that ICOS plays a significant role in orchestrating the innate immune
      response to S. aureus and other airway pathogens, and could be a potential
      immunomodulatory target to attenuate S. aureus-related immunopathology.

PMID- 29378031
TI  - Stage of disease in hepatitis B virus infection in Zambian adults is associated
      with large cell change but not well defined using classic biomarkers.
AB  - Background: Hepatocellular malignancy in young adults is a prominent feature of
      hepatitis B virus (HBV) infection in southern Africa. Here we report a cross
      sectional study of liver pathology correlated with biomarkers in adults with HBV
      infection in Zambia. Methods: We analysed liver biopsies from Zambian patients
      with persistent HBV infection. Results: We analysed 104 patients with HBV
      infection and evidence of liver disease. We obtained liver biopsies from 53
      adults; of these, 12 (23%) were hepatitis B e antigen seropositive. The genotype
      was evenly distributed between A and E. One biopsy showed malignancy. Stage was 3
      or more in 11 of 52 (21%) biopsies free of malignancy and lobular inflammation
      was found in 50 (94%). Neither alanine aminotransferase (ALT) nor the gamma
      glutamyl transferase:platelet ratio (GPR) were correlated with the stage of
      disease but were correlated with total Ishak score (rho=0.47, p=0.0004 and
      rho=0.33, p=0.02, respectively). Large cell change was observed in 10 of 11
      biopsies with fibrosis stage 3 or more and 16 of 41 with early disease (p=0.005).
      Serum alpha-fetoprotein was elevated, although still within the normal range, in
      patients with large cell change (median 3.6 [interquartile range {IQR} 1.6-5.1])
      compared with those without (1.7 [IQR 1.0-2.8]; p=0.03). Neither ALT nor GPR
      predicted large cell change. Conclusions: Large cell change was common in young
      HBV-infected adults in Zambia. Only serum alpha-fetoprotein was identified as a
      biomarker of this phenotype.

PMID- 29378033
TI  - Cervical Cancer Markers: Epigenetics and microRNAs.
AB  - Gynecologic malignant neoplasms are a severe health problem among female
      patients, of which cervical cancer (CC), in particular, is a common disease
      leading to high mortality rates. Despite extensive attempts by researchers to
      solve the molecular mystery of CC, the mechanisms of its pathogenesis remain
      unclear. Tumor markers used in the clinical laboratory, such as squamous cell
      carcinoma (SCC), cancer antigen (CA)-125, and CA19-9, provide some help in
      diagnosing patients with CC. However, finding new molecular markers with high
      sensitivity and specificity is necessary. This review focuses on the role of
      epigenetic changes, particularly microRNAs (miRNAs), to CC. Several miRNAs that
      associated with CC potentially have the advantage of being early biomarkers.
      Moreover, altered serum miRNAs or single nucleotide polymorphisms in miRNA
      patterns may predict disease progression.

PMID- 29378032
TI  - Single-Base Resolution Map of Evolutionary Constraints and Annotation of
      Conserved Elements across Major Grass Genomes.
AB  - Conserved noncoding sequences (CNSs) are evolutionarily conserved DNA sequences
      that do not encode proteins but may have potential regulatory roles in gene
      expression. CNS in crop genomes could be linked to many important agronomic
      traits and ecological adaptations. Compared with the relatively mature exon
      annotation protocols, efficient methods are lacking to predict the location of
      noncoding sequences in the plant genomes. We implemented a computational pipeline
      that is tailored to the comparisons of plant genomes, yielding a large number of
      conserved sequences using rice genome as the reference. In this study, we used 17
      published grass genomes, along with five monocot genomes as well as the basal
      angiosperm genome of Amborella trichopoda. Genome alignments among these genomes
      suggest that at least 12.05% of the rice genome appears to be evolving under
      constraints in the Poaceae lineage, with close to half of the evolutionarily
      constrained sequences located outside protein-coding regions. We found evidence
      for purifying selection acting on the conserved sequences by analyzing
      segregating SNPs within the rice population. Furthermore, we found that known
      functional motifs were significantly enriched within CNS, with many motifs
      associated with the preferred binding of ubiquitous transcription factors. The
      conserved elements that we have curated are accessible through our public
      database and the JBrowse server. In-depth functional annotations and evolutionary
      dynamics of the identified conserved sequences provide a solid foundation for
      studying gene regulation, genome evolution, as well as to inform gene isolation
      for cereal biologists.

PMID- 29378034
TI  - Characterization of inappetent sheep in a feedlot using radio-tracking
      technology.
AB  - The feeding and drinking behaviours of sheep were monitored using RFID technology
      at a commercial pre-embarkation feedlot in Western Australia with the aim of
      characterizing feeding and drinking patterns of inappetent sheep that might allow
      them to be treated. Feeding and drinking behaviours of sheep were compared with
      their survival and change in body condition. Patterns of number of visits and the
      time spent at feed and water troughs were analyzed for a total of 8,206 sheep,
      representing four consignments that were monitored for a range of 6-31 d. Data
      for feeding and drinking behaviours were compared for the first 6 d. For animals
      that were alive at exit, 18.9% of sheep attended the feed trough for less than
      0.25 h d-1 (15 min per day) on day 1; this decreased to only 2.4% of sheep by day
      6. Of the sheep monitored, 0.93% died (n = 76); Salmonella spp. infection was the
      leading cause of death (n = 40; 52.6% of all deaths) across all months and was
      accompanied with inanition. There was marked variability in the average time
      spent at the feed trough for sheep that died eventually from salmonella/inanition
      (contributing to the lack of statistical difference in time spent at feed trough
      between sheep dying from different causes; P = 0.056). Over half (55%) of the
      animals diagnosed with salmonella/inanition spent an average of less than 0.50 h
      d-1 (30 min per day) and 45% less than 0.25 h d-1 at the feed trough. There was a
      negative correlation (r) in time spent at the feed trough overtime for individual
      sheep that died from salmonella/inanition, indicating that these individuals went
      off their feed. This pattern was not evident for animals that died from other
      causes (significant difference in r values between five categories of cause of
      death; P = 0.040). Characterization of feeding behaviour of sheep that died from
      salmonella/inanition therefore appears to require more than simply monitoring
      daily intake. There was no difference in time spent at water troughs between
      sheep that died or were alive at exit (average 0.30 +/- 0.23 h d-1). This study
      reveals that the patterns of feeding and drinking behaviours during pre
      embarkation feedlotting do not readily allow identification of animals that
      warrant singling out for veterinary care or alternative feed arrangements. This
      result highlights the need for experienced stockmanship in handling these
      animals.

PMID- 29378035
TI  - Skin autofluorescence, arterial stiffness and Framingham risk score as predictors
      of clinical outcome in chronic kidney disease patients: a cohort study.
AB  - Background: The risk of cardiovascular disease (CVD) is predicted by Framingham's
      CVD risk scores (FRS) but the high CVD-related mortality in patients with chronic
      kidney disease (CKD) is only partially explained by traditional CVD risk markers.
      Therefore, there is a need to explore whether other CVD risk markers may improve
      risk prediction. Although arterial stiffness measured by augmentation index (AIx)
      and tissue content of advanced glycation end-products (AGEs) measured by skin
      autofluorescence (SAF) are two biomarkers that associate with CVD and mortality
      in CKD, it is not known how they compare with FRS. We evaluated associations
      between SAF, AIx and FRS, and their associations with CVD and mortality in CKD
      patients. Methods: SAF (AGE Reader) and AIx (SphygmoCor; adjusted for 75 heart
      beats per minute) were measured in 261 clinically stable and extensively
      phenotyped patients with CKD Stage 5 (median age 56 years, 66% male, 20%
      diabetes; 130 non-dialysed, 93 patients on peritoneal dialysis and 38 patients on
      haemodialysis). Multivariate receiver operator characteristics (ROC) curve
      analysis and multivariate Cox models followed by C-statistics were used to
      evaluate CVD-related and all-cause mortality risk associated with SAF, AIx and
      FRS during follow-up for median 25 months with 46 deaths. Results: In
      multivariate regression analysis, SAF associated with FRS, haemoglobin, fat body
      mass index and CVD, and inversely with per cent handgrip strength (HGS). AIx
      associated with FRS, and inversely with per cent HGS. Associations of SAF and AIx
      with high-sensitivity C-reactive protein (hsCRP), serum albumin, statin therapy
      and renal replacement therapy were not statistically significant. In ROC
      analysis, area under the curve (AUC) for CVD mortality ranged from AUC = 0.72
      (AIx and FRS, respectively) to AUC = 0.78 (FRS + AIx), and for all-cause
      mortality from AUC = 0.70 (AIx) to AUC = 0.79 (FRS + AIx). In multivariate Cox
      analysis, after adjusting for 1-standard deviation (1-SD) of FRS, 1-SD increase
      of SAF associated with all-cause mortality and 1-SD increase of AIx associated
      with CVD mortality and all-cause mortality. After further adjustments for hsCRP,
      albumin and presence of CVD, AIx (but not SAF) remained independently associated
      with CVD mortality, hazard ratio (HR) 2.14 [95% confidence interval (95% CI) 1.18
      3.89] and all-cause mortality, HR 1.74 (95% CI 1.16-2.60). Conclusions: In
      patients with CKD Stage 5, SAF and aortic stiffness associated with mortality,
      independently of FRS. After adjusting for additional confounders including
      inflammation, aortic stiffness remained as an independent predictor of outcome.
      Since the contribution of SAF and aortic stiffness compared with FRS in ROC curve
      analysis was relatively modest, this underlines the importance of traditional CVD
      risk factors in CKD.

PMID- 29378036
TI  - Dietary Glycemic Index and Glycemic Load Are Positively Associated with Oxidative
      Stress among Premenopausal Women.
AB  - Background: Diets with a high glycemic index (GI) and glycemic load (GL) have
      been hypothesized to increase oxidative stress, but the limited human studies are
      inconsistent. Objective: The aim of this cross-sectional study was to investigate
      associations between dietary GI, GL, and carbohydrate intake and oxidative
      stress, as measured by F2-isoprostanes (F2-IsoPs). Methods: Concentrations of F2
      IsoP and its metabolite (15-F2t-IsoP-M) were measured in urine samples collected
      at enrollment from 866 premenopausal women (aged 35-54 y) participating in the
      Sister Study. Total carbohydrate intake and dietary GI and GL were assessed using
      a validated food frequency questionnaire. Urinary F2-IsoP and 15-F2t-IsoP-M
      concentrations were compared across quintiles of carbohydrate intake, GI, and GL
      using multivariable linear regression models. Results: Urinary F2-IsoP
      concentrations were positively associated with dietary GI (P-trend = 0.023), and
      both F2-IsoP and 15-F2t-IsoP-M concentrations were positively associated with GL
      (F2-IsoP: P-trend < 0.001; 15-F2t-IsoP-M: P-trend < 0.001) and total carbohydrate
      intake (F2-IsoP: P-trend = 0.012; 15-F2t-IsoP-M: P-trend < 0.001). Stratified
      analyses suggested that a positive association between GI and urinary 15-F2t-IsoP
      M concentrations was present among women with a body mass index [BMI (in kg/m2)]
      >=30.0, but not among those with a BMI of <25.0 or 25.0-29.9 (P-interaction =
      0.01). Conclusions: Our cross-sectional analyses in a sample of premenopausal
      women support hypothesized relations between high dietary GI and GL and oxidative
      stress, as assessed by urinary F2-IsoP and 15-F2t-IsoP-M concentrations. Given
      potential associations between oxidative stress and the development of
      cardiovascular disease and type 2 diabetes, our findings may have important
      implications for reducing chronic disease risk.

PMID- 29378037
TI  - Consuming Green Tea at Least Twice Each Day Is Associated with Reduced Odds of
      Chronic Obstructive Lung Disease in Middle-Aged and Older Korean Adults.
AB  - Background: The frequent consumption of green tea has been shown to have
      antioxidant and anti-inflammatory effects and to reduce the risk of lung cancer
      and type 2 diabetes. However, few studies have investigated the relation between
      green tea consumption and the risk of chronic obstructive lung disease (COPD).
      Objective: This study aimed to examine the association between green tea intake
      and COPD with the use of a nationwide representative database. Methods: This
      study was designed as a cross-sectional survey with the use of data from the
      Korean National Health and Nutritional Examination Survey collected between 2008
      and 2015. Of these participants, 13,570 participants aged >=40 y were included in
      the study population. COPD was defined as forced expiratory volume in 1 s (FEV1)
      divided by forced vital capacity (FVC) <0.70. Multiple linear and logistic
      regression models were used to examine the association between the frequency of
      green tea intake and risk of COPD after adjusting for age, sex, body mass index,
      smoking status, alcohol consumption, physical activity, and socioeconomic status.
      Results: The incidence of COPD decreased from 14.1% to 5.9% with increased
      frequency of green tea intake from never to >=2 times/d (P < 0.001). In the fully
      adjusted multiple linear regression model, the frequency of green tea intake
      showed a linear dose-response relation with FEV1/FVC (P-trend = 0.031). In the
      multiple logistic regression model, the OR for COPD among people who consumed
      green tea >=2 times/d was 0.62 (95% CI: 0.40, 0.97), compared with those who
      never drank green tea, after adjusting for all covariates. Conclusion: This study
      suggests that the consumption of green tea >=2 times/d is associated with a
      reduced risk of COPD in Korean populations.

PMID- 29378038
TI  - Cashew Nut Consumption Increases HDL Cholesterol and Reduces Systolic Blood
      Pressure in Asian Indians with Type 2 Diabetes: A 12-Week Randomized Controlled
      Trial.
AB  - Background: There is increasing evidence that nut consumption decreases the risk
      of cardiovascular disease. However, there are few data on the health effects of
      cashew nuts among adults with type 2 diabetes (T2DM). Objective: The study aimed
      to investigate the effects of cashew nut supplementation on glycemia, body
      weight, blood pressure, and lipid profile in Asian Indians with T2DM. Methods: In
      a parallel-arm, randomized controlled trial, 300 adults with T2DM [mean +/- SD
      age: 51 +/- 9.3 y; body mass index (BMI; in kg/m2): 26.0 +/- 3.4; 55% male] were
      randomly assigned to receive advice to follow a standard diabetic diet (control)
      or similar advice plus 30 g cashew nuts/d (intervention) for 12 wk. The
      macronutrient composition of the prescribed diabetic diet was 60-65% energy from
      carbohydrates, 15-25% from fat, and the rest from protein. Differences between
      groups in changes in anthropometric and biochemical variables were analyzed using
      linear models with robust variance estimation under an assumed independence
      working correlation. Results: Participants in the intervention group had a
      greater decrease in systolic blood pressure from baseline to 12 wk than did
      controls (-4.9 +/- 13.7 compared with -1.7 +/- 11.6 mm Hg; P = 0.04) and a
      greater increase in plasma HDL cholesterol compared with controls (+1.7 +/- 5.6
      compared with +0.1 +/- 4.6 mg/dL; P = 0.01). There were no differences between
      the groups with respect to changes in body weight, BMI, blood lipid, and glycemic
      variables. Plasma oleic acid concentrations and self-reported dietary intake of
      nuts, oleic acid, and monounsaturated fatty acids suggested excellent compliance
      with the nut consumption. Conclusion: Cashew nut supplementation in Asian Indians
      with T2DM reduced systolic blood pressure and increased HDL cholesterol
      concentrations with no deleterious effects on body weight, glycemia, or other
      lipid variables. This study was registered at the clinical trial registry of
      India as CTRI/2017/07/009022.

PMID- 29378039
TI  - Dietary Potential Renal Acid Load Is Positively Associated with Serum Uric Acid
      and Odds of Hyperuricemia in the German Adult Population.
AB  - Background: Initial interventional data indicate that a reduction in dietary acid
      load (e.g., by an increased consumption of alkalizing fruit and vegetables) can
      increase renal uric acid excretion and decrease serum uric acid (SUA). Objective:
      Against this background, we examined the association between dietary potential
      renal acid load (PRAL) and SUA in a representative population sample. Methods:
      Cross-sectional analyses were performed in 6894 participants (aged 18-79 y) of
      the German Health Interview and Examination Survey for Adults (DEGS1). Dietary
      intake was assessed with a food-frequency questionnaire. Nutritive acid load and
      the intake of uric acid equivalents (UAEs) were characterized by assigning PRAL
      and UAE values to reported food consumption. In multiple linear regression
      models, the associations of PRAL, UAEs, and relevant food groups with SUA were
      analyzed. Multiple logistic regressions were used to calculate ORs for
      hyperuricemia comparing lower and upper tertiles of the predictors. Results:
      After adjustment for relevant confounders, PRAL (P = 0.003), alcohol (P <
      0.0001), and UAE (P = 0.03) intakes were positively associated with SUA, whereas
      the intake of dairy products and fruit and vegetables was inversely associated
      (both P < 0.0001). Subgroup analyses among participants without interacting
      medication use confirmed these results. In addition, participants with lower PRAL
      had lower odds for hyperuricemia (OR: 0.60; 95% CI: 0.43, 0.83). Conclusions:
      Apart from observing known dietary influences on SUA, we found in this population
      based, cross-sectional study in adults that low PRAL may represent a potentially
      SUA-reducing dietary pattern. This highlights dietary alkalization as a possible
      nonpharmacologic option to influence elevated SUA concentrations.

PMID- 29378040
TI  - Postprandial Metabolism and Appetite Do Not Differ between Lean Adults that Eat
      Breakfast or Morning Fast for 6 Weeks.
AB  - Background: It remains unknown whether sustained daily feeding-fasting patterns
      modify the acute response to specific feedings on a given day. Objective: We
      conducted a randomized controlled trial to establish if daily breakfast
      consumption or fasting until noon modifies the acute metabolic and appetitive
      responses to a fixed breakfast and ad libitum lunch. Methods: With the use of a
      parallel group design, we randomly assigned 31 healthy, lean men and women (22-56
      y) to 6 wk of either consuming >=700 kcal of self-selected items before 1100 or
      fasting (0 kcal) until 1200 daily. Following 48 h of diet and physical activity
      standardization, we examined metabolic and appetite responses to a standardized
      breakfast and ad libitum lunch before and after the intervention. Data were
      analyzed using 3- and 2-way ANCOVA. Results: Systemic concentrations of energy
      balance regulatory hormones total and acylated ghrelin, leptin, and peptide
      tyrosine-tyrosine) responded similarly to breakfast and lunch before and after 6
      wk of either morning fasting or regular breakfast, with the exception of a
      tendency for increased glucagon-like peptide-1 concentrations from baseline to
      follow-up in the Breakfast Group compared with a decrease over that period in the
      Fasting Group [P = 0.06, partial eta squared value (n2) = 0.16]. Subjective
      appetite sensations also did not differ over the course of the day, and ad
      libitum energy intake at lunch was not systematically affected by either
      intervention, decreasing by 27 kcal (95% CI: -203, 149 kcal) with fasting and by
      77 kcal (95% CI: -210, 56 kcal) with breakfast. Similarly, glycemic, insulinemic,
      lipemic, and thermogenic responses to breakfast and lunch were very stable at
      baseline and follow-up and, thus, did not differ between treatment groups.
      Conclusions: Our results indicate that a sustained period of either extended
      morning fasting or eating a daily breakfast has minimal effect upon acute
      metabolic and appetite responses in lean adults. This trial was registered at
      www.isrctn.org as ISRCTN31521726.

PMID- 29378041
TI  - Better Diet Quality during Pregnancy Is Associated with a Reduced Likelihood of
      an Infant Born Small for Gestational Age: An Analysis of the Prospective New
      Hampshire Birth Cohort Study.
AB  - Background: Birth weight has a U-shaped relation with chronic disease. Diet
      quality during pregnancy may impact fetal growth and infant birth weight, yet
      findings are inconclusive. Objective: We examined the relation between maternal
      diet quality during pregnancy and infant birth size among women enrolled in a
      prospective birth cohort. Methods: Women 18-45 y old with a singleton pregnancy
      were recruited at 24-28 wk of gestation from prenatal clinics in New Hampshire.
      Women completed a validated food frequency questionnaire at enrollment. Diet
      quality was computed as adherence to the Alternative Healthy Eating Index. Infant
      birth outcomes (sex, head circumference, weight, and length) were extracted from
      medical records. Weight-for-length z scores, low birth weight, macrosomia, and
      size for gestational age [small for gestational age (SGA) or large for
      gestational age (LGA)] were computed. Multivariable regression models fit each
      outcome on quartiles of diet quality, adjusted for covariates. Models were
      computed overall and stratified by smoking status. Results: Analyses included 862
      women and infants with complete data. Lower diet quality was associated with
      lower maternal education, being a smoker, prepregnancy obesity status, and lack
      of exercise during pregnancy. Overall, 3.4% of infants were born with a low birth
      weight, 12.1% with macrosomia, 4.6% were SGA, and 8.7% were LGA. In an adjusted
      model, increased diet quality appeared linearly associated with a reduced
      likelihood of SGA (P-trend = 0.03), although each quartile comparison did not
      reach statistical significance. Specifically, ORs for SGA were 0.89 (95% CI:
      0.37, 2.15), 0.73 (95% CI: 0.28, 1.89), and 0.35 (95% CI: 0.11, 1.08) for each
      increasing quartile of diet quality compared to the lowest quartile. Similar
      trends for SGA were observed among non-smokers (n = 756; P-trend = 0.07). Also
      among non-smokers, increased diet quality was associated with lower infant birth
      weight (P-trend = 0.03) and a suggested reduction in macrosomia (P-trend = 0.07).
      Conclusions: Increased diet quality during pregnancy was related to a reduced
      risk of SGA in this cohort of pregnant women from New Hampshire. Additional
      studies are needed to elucidate the relation between maternal diet quality and
      macrosomia.

PMID- 29378042
TI  - Vitamin E Status Is Inversely Associated with Risk of Incident Tuberculosis
      Disease among Household Contacts.
AB  - Background: Few studies have previously assessed how pre-existing vitamin E
      status is associated with risk of tuberculosis (TB) disease progression.
      Objective: We evaluated the association between baseline plasma concentrations of
      3 vitamin E isomers (alpha-tocopherol, gamma-tocopherol, and delta-tocopherol)
      and TB disease risk. Methods: We conducted a case-control study nested within a
      longitudinal cohort of household contacts (HHCs) of pulmonary TB cases in Lima,
      Peru. We defined cases as HHCs who developed active TB disease >=15 d after the
      diagnosis of the index patient, and we matched each case to 4 control cases who
      did not develop active TB based on age by year and gender. We used univariate and
      multivariate conditional logistic regression to calculate ORs for incident TB
      disease by plasma concentrations of alpha-tocopherol, gamma-tocopherol, and delta
      tocopherol. Results: Among 6751 HIV-negative HHCs who provided baseline blood
      samples, 180 developed secondary TB during follow-up. After controlling for
      possible confounders, we found that baseline alpha-tocopherol deficiency
      conferred increased risk of incident TB disease (adjusted OR: 1.59; 95% CI: 1.02,
      2.50; P = 0.04). Household contacts in the lowest tertile of delta-tocopherol
      were also at increased risk of progression to TB disease compared to those in the
      highest tertile (tertile 1 compared with tertile 3, adjusted OR: 2.29; 95% CI:
      1.29, 4.09; P-trend = 0.005). We found no association between baseline
      concentration of gamma-tocopherol and incident TB disease. Conclusions: Vitamin E
      deficiency was associated with an increased risk of progression to TB disease
      among HHCs of index TB cases. Assessment of vitamin E status among individuals at
      high risk for TB disease may play a role in TB control efforts.

PMID- 29378043
TI  - The Socioeconomic Disparities in Intakes and Purchases of Less-Healthy Foods and
      Beverages Have Changed over Time in Urban Mexico.
AB  - Background: To our knowledge, the association between diet and socioeconomic
      status (SES), using both purchase and intake data, in the Mexican population has
      not been examined, which is particularly important given the high prevalence of
      diet-related diseases in Mexico. Objective: Our objective was to examine the SES
      diet relation using household food purchases and individual food intake data.
      Methods: We analyzed purchases of packaged food and beverages of 5240 households
      with the use of the 2012-2014 Nielsen Mexico Consumer Panel Service Dataset,
      representative of urban areas. Likewise, we examined 9672 individuals over 2 y
      with food and beverage intake information collected using a single 24-h recall as
      part of the Mexican National Health and Nutrition Survey 2012. Multivariate
      linear regression models were conducted to predict per capita daily purchases and
      intakes of food and beverages classified as healthy and less healthy by SES, and
      adjusting for sociodemographic variables. Results: Per capita daily purchases of
      healthy and less-healthy foods were, on average, 142% and 55% higher in high-
      than in low-SES households, respectively, from 2012 to 2014 (P < 0.05). Intakes
      of healthy and less-healthy foods in urban areas were, on average, 7% and 136%
      higher in high- than in low-SES groups (P < 0.05). Per capita daily purchases of
      healthy beverages were, on average, 56% higher in high- than in low-SES
      households from 2012 to 2014 (P < 0.05), whereas purchases of less-healthy
      beverages were 27% and 17% higher in low- than in high-SES households in 2012 and
      2014, respectively (P < 0.05). Per capita daily intake of healthy beverages was
      33% higher in high- than in low-SES groups (P < 0.05). Conclusion: Higher-SES
      groups from urban areas had greater purchases and intakes of less-healthy foods
      and healthy beverages. Lower-SES households had greater purchases of less-healthy
      beverages, but also had the largest reduction in these purchases from 2012 to
      2014, which could be associated with the beverage tax implemented in Mexico in
      2014.

PMID- 29378044
TI  - Impact of Dietary Fiber Consumption on Insulin Resistance and the Prevention of
      Type 2 Diabetes.
AB  - Large prospective cohort studies consistently show associations of a high dietary
      fiber intake (>25 g/d in women and >38 g/d in men) with a 20-30% reduced risk of
      developing type 2 diabetes (T2D), after correction for confounders. It is less
      well recognized that these effects appear to be mainly driven by high intakes of
      whole grains and insoluble cereal fibers, which typically are nonviscous and do
      not relevantly influence postprandial glucose responses [i.e., glycemic index
      (GI)] or are strongly fermented by the gut microbiota in the colon. In contrast,
      a dietary focus on soluble, viscous, gel-forming, more readily fermentable fiber
      intakes derived from fruit and certain vegetables yields mixed results and
      generally does not appear to reduce T2D risk. Although disentangling types of
      fiber-rich foods and separating these from possible effects related to the GI is
      an obvious challenge, the common conclusion that key metabolic effects of high
      fiber intake are explained by mechanisms that should mainly apply to the soluble,
      viscous type can be challenged. More recently, studies in humans and animal
      models focused on gaining mechanistic insights into why especially high-cereal
      fiber (HCF) diets appear to improve insulin resistance (IR) and diabetes risk.
      Although effects of HCF diets on weight loss are only moderate and comparable to
      other types of dietary fibers, possible novel mechanisms have emerged, which
      include the prevention of the absorption of dietary protein and modulation of the
      amino acid metabolic signature. Here we provide an update of our previous review
      from 2008, with a focus on mechanistic insights of how HCF diets may improve IR
      and the risk of developing T2D.

PMID- 29378045
TI  - Infant Serum and Maternal Milk Vitamin B-12 Are Positively Correlated in Kenyan
      Infant-Mother Dyads at 1-6 Months Postpartum, Irrespective of Infant Feeding
      Practice.
AB  - Background: Vitamin B-12 is an essential nutrient required for many functions
      including DNA synthesis, erythropoiesis, and brain development. If maternal milk
      vitamin B-12 concentrations are low, infants may face elevated risks of
      deficiency when exclusively breastfed. Objective: We evaluated cross-sectional
      associations between infant serum vitamin B-12 concentrations and maternal milk
      vitamin B-12 concentrations at 1-6 mo postpartum among an unsupplemented
      population in rural western Kenya, and assessed biological demographic, and
      dietary characteristics associated with adequate infant serum vitamin B-12.
      Methods: We modeled 1) infant serum vitamin B-12 using maternal milk vitamin B-12
      concentration with linear regression; and 2) adequate (>220 pmol/L) infant serum
      vitamin B-12 using hypothesized biological, demographic, and dietary predictors
      with logistic regression. In both models, we used generalized estimating
      equations to account for correlated observations at the cluster-level. Results:
      The median (quartile 1, quartile 3) infant serum vitamin B-12 concentration was
      276 pmol/L (193, 399 pmol/L) and approximately one-third of infants had serum
      vitamin B-12 <=220 pmol/L, indicating that they were vitamin B-12 depleted or
      deficient. There was a positive correlation between maternal milk and infant
      serum vitamin B-12 (r = 0.36, P < 0.001) and in multivariable analyses, maternal
      milk vitamin B-12 concentration was significantly associated with infant serum
      vitamin B-12 adequacy (P-trend = 0.03). Conclusions: Despite a high prevalence
      (90%) of maternal milk vitamin B-12 concentrations below the level used to
      establish the Adequate Intake (<310 pmol/L), there was a low prevalence of infant
      vitamin B-12 deficiency. We found few factors that were associated with infant
      vitamin B-12 adequacy in this population, including infant feeding practices,
      although maternal vitamin B-12 status was not measured. The contribution of
      maternal milk to infant vitamin B-12 status remains important to quantify across
      populations, given that maternal milk vitamin B-12 concentration is modifiable
      with supplementation. This trial was registered at clinicaltrials.gov as
      NCT01704105.

PMID- 29378047
TI  - Early-Life Nutrition Is Associated Positively with Schooling and Labor Market
      Outcomes and Negatively with Marriage Rates at Age 20-25 Years: Evidence from the
      Andhra Pradesh Children and Parents Study (APCAPS) in India.
AB  - Background: India's Integrated Child Development Services (ICDS) is among the
      world's largest public nutritional programs, providing daily nutritional
      supplements and other public health and educational services to pregnant and
      nursing women, children aged <6 y, and adolescent girls. Objective: We estimated
      the long-term association between early-childhood ICDS nutrition and adult
      outcomes. Methods: We used follow-up data from a controlled nutritional trial
      conducted during 1987-1990 in 29 villages near the city of Hyderabad. In 15
      intervention villages, a balanced protein-calorie supplement-made from locally
      available corn-soya ingredients and called upma-was offered to pregnant women and
      to children <6 y old. No supplement was offered in the 14 control villages.
      During 2010-2012, adults born during the trial were re-surveyed (n = 715 in the
      intervention arm and n = 645 in the control arm). We used probit regression and
      propensity score-matching methods to estimate the association between birth in an
      intervention village and rates of secondary and graduate education completion,
      marriage, and employment or enrollment in higher education of these adults.
      Results: Adults born in the intervention group during the trial, compared with
      the control group, were 9% (95% CI: 0.04, 0.14; P < 0.01) more likely to complete
      secondary school and 11% (95% CI: 0.06, 0.15; P < 0.01) more likely to complete
      graduate education, were 6% (95% CI: -0.11, -0.01; P < 0.05) less likely to be
      ever-married at age 20-25 y, and were 5% (95% CI: 0, 0.11; P < 0.05) more likely
      to be employed or enrolled in higher education. The estimated associations for
      graduate education completion and employment-study rates were greater for men,
      whereas the associations for secondary education and ever-married rates were
      greater for women. Conclusion: Exposure to nutritional supplement in utero or
      during the first 3 y of life was associated with improved adult educational and
      employment outcomes and lower marriage rates in India.

PMID- 29378046
TI  - A 10-Food Group Dietary Diversity Score Outperforms a 7-Food Group Score in
      Characterizing Seasonal Variability and Micronutrient Adequacy in Rural Zambian
      Children.
AB  - Background: Dietary diversity scores and dichotomous indicators derived from them
      are widely used to assess dietary quality, and specific scoring methods have been
      recommended for women and 6- to 23-mo-old children. However, there is no specific
      score recommended for older children and the effect of seasonal dietary changes
      on score performance is not well documented. Objective: We assessed performance
      of 2 recommended dietary diversity scores as indicators of dietary quality over 3
      seasons. Methods: We conducted 7 repeat 24-h dietary recalls among 4- to 8-y-old
      rural Zambian children (n = 200) over 6 mo. Dietary diversity was assessed using
      a 7-food group score for assessing infant and young child feeding (DDS-IYCF) and
      a 10-food group score for use among women of reproductive age (DDS-W).
      Micronutrient intake adequacy was described by mean probability of adequacy (MPA)
      over 11 micronutrients. Longitudinal models were fit to test the association
      between each score and MPA overall and by season. Receiver operating
      characteristic (ROC) curves were used to describe indicator performance of each
      score. Results: Mean +/- SE scores were 4.11 +/- 0.03 for DDS-IYCF and 4.39 +/-
      0.03 for DDS-W. Both scores varied by season, but DDS-W better reflected seasonal
      dietary changes. Across seasons, MPA increased 1-6 percentage points/unit
      increase in DDS-IYCF or 1-10 percentage points for DDS-W (P < 0.05). Score
      performance as a predictor of MPA > 0.75 was moderate, with area under the ROC
      curve values by season ranging from 0.63 to 0.77 for DDS-IYCF and from 0.66 to
      0.72 for DDS-W. Conclusions: DDS-W performed better than DDS-IYCF in
      characterizing seasonal variability and micronutrient adequacy among rural
      Zambian children.

PMID- 29378048
TI  - Associations between Diet Quality Scores and Risk of Postmenopausal Estrogen
      Receptor-Negative Breast Cancer: A Systematic Review.
AB  - Background: Estrogen receptor-negative (ER-) breast cancer tends to have poorer
      prognosis than estrogen receptor-positive breast cancer. A number of studies have
      examined the association between diet quality as measured by various diet quality
      scores and the risk of ER- breast cancer. Objective: This systematic review aimed
      to summarize existing evidence on this topic. Methods: Medline and Embase
      searches were conducted until 2 April 2017 for cohort and case-control studies on
      diet quality scores and ER- breast cancer. Results: We included 6 prospective
      cohort studies and 1 case-control study on postmenopausal ER- breast cancer: 4
      from Europe and 3 from the United States. There were 12 different diet quality
      scores: 2 versions of the Dietary Inflammatory Index, 4 versions of the
      Mediterranean diet score, the Healthy Eating Index, the Alternate Healthy Eating
      Index, the Dietary Approaches to Stop Hypertension (DASH) score, and 3 versions
      of low-carbohydrate diet scores that differentiate between different sources of
      protein and fat. Of the 4 studies on Mediterranean diet scores, 3 showed a
      significant inverse association with postmenopausal ER- breast cancer, whereas no
      consistent association was observed with the other diet quality scores. Although
      most diet quality scores in this review share similar food components, most of
      the non-Mediterranean diet scores were represented by only 1 study each, and the
      associations with postmenopausal ER- breast cancer were mixed. All studies were
      adjusted for multiple covariates. Conclusion: This systematic review shows mixed
      results for an association between a variety of diet quality scores and
      postmenopausal ER- cancer. However, results from different versions of the
      Mediterranean diet scores are more consistent and suggest an inverse relation
      with ER- breast cancer.

PMID- 29378050
TI  - Corrigendum for Takeda K et al. Effects of a fermented milk drink containing
      Lactobacillus casei strain Shirota on the human NK-cell activity. J Nutr
      2007;137(Suppl):791S-3S.

PMID- 29378049
TI  - The delta13C Value of Fingerstick Blood Is a Valid, Reliable, and Sensitive
      Biomarker of Sugar-Sweetened Beverage Intake in Children and Adolescents.
AB  - Background: Reliance on self-reported dietary intake methods is a commonly cited
      research limitation, and dietary misreporting is a particular problem in children
      and adolescents. Objective indicators of dietary intake, such as dietary
      biomarkers, are needed to overcome this research limitation. The added sugar (AS)
      biomarker delta13C, which measures the relative abundance of 13C to 12C, has
      demonstrated preliminary validity in adults. Objective: The purpose of this
      investigation was to determine the comparative validity, test-retest reliability,
      and sensitivity of the delta13C biomarker to detect AS and sugar-sweetened
      beverage (SSB) intake using fingerstick blood samples in children and
      adolescents. Methods: Children (aged 6-11 y, n = 126, 56% male, mean +/- SD age:
      9 +/- 2 y) and adolescents (aged 12-18 y, n = 200, 44% male, mean +/- SD age: 15
      +/- 2 y) completed 4 testing sessions within a 3-wk period. Participants' height,
      weight, demographic characteristics, and health history were determined at the
      first session; 24-h recalls were obtained at each visit and fingerstick blood
      samples were collected at visits 1 and 3. Samples were analyzed for delta13C
      value using natural abundance stable isotope mass spectrometry. delta13C value
      was compared with dietary outcomes in the full sample, and in child and
      adolescent subgroups. t Tests and correlational analyses were used to assess
      biomarker validity and reliability, whereas logistic regression and area under
      the receiver-operator characteristic curve (AUC) were used to evaluate
      sensitivity. Results: Reported mean +/- SD AS consumption was 82.2 +/- 35.8 g/d
      and 329 +/- 143 kcal/d, and SSB consumption was 222 +/- 243 mL/d and 98 +/- 103
      kcal/d. Mean delta13C value was -19.65 +/- 0.690/00, and was lower in children
      than in adolescents (-19.80 +/- 0.670/00 compared with -19.56 +/- 0.670/00, P =
      0.002). delta13C values were similar across sessions (visit 1: -19.66 +/-
      0.680/00; visit 3: -19.64 +/- 0.680/00; r = 0.99, P < 0.001) and were associated
      (P < 0.001) with intake of total AS (grams, kilocalories: r = 0.29) and SSB
      (milliliters, kilocalories: r = 0.35). The biomarker was able to better
      discriminate between high and low SSB consumers than high and low AS consumers,
      as demonstrated by the AUC (0.75 and 0.62, respectively). Conclusions: The
      delta13C biomarker is a promising, minimally invasive, objective biomarker of SSB
      intake in children and adolescents. Further evaluation using controlled feeding
      designs is warranted. Registered at clinicaltrials.gov as NCT02455388.

PMID- 29378051
TI  - Short-Term Overfeeding with Dairy Cream Does Not Modify Gut Permeability, the
      Fecal Microbiota, or Glucose Metabolism in Young Healthy Men.
AB  - Background: High-fat diets (HFDs) have been linked to low-grade inflammation and
      insulin resistance. Objective: The main purpose of the present study was to
      assess whether acute overfeeding with an HFD affects insulin sensitivity, gut
      barrier function, and fecal microbiota in humans. Methods: In a prospective
      intervention study, 24 healthy men [mean +/- SD: age 23.0 +/- 2.8 y, body mass
      index (in kg/m2) 23.0 +/- 2.1] received an HFD (48% of energy from fat) with an
      additional 1000 kcal/d (as whipping cream) above their calculated energy
      expenditure for 7 d. Insulin sensitivity (hyperinsulinemic euglycemic clamp), gut
      permeability (sugar and polyethylene glycol absorption tests, plasma zonulin),
      and gut microbiota profiles (high-throughput 16S rRNA gene sequencing) were
      assessed before and after overfeeding, and 14 d after intervention. Additionally,
      inflammation markers such as high-sensitivity C-reactive protein,
      lipopolysaccharide-binding protein, leptin, high-molecular-weight adiponectin,
      calprotectin, regulated on activation normal, T cell expressed and secreted
      (RANTES), and monocyte chemoattractant protein-1 were measured in plasma by
      ELISA. Finally, lipid parameters were analyzed in serum by a laboratory service.
      Results: Although participants gained 0.9 +/- 0.6 kg (P < 0.001) body weight,
      overnutrition was not associated with a significant change in insulin sensitivity
      (M value and glucose disposal). Overfeeding for 7 d resulted in elevated serum
      total (10.2%), LDL (14.6%) and HDL (14.8%) cholesterol concentrations (P < 0.01).
      In contrast, fasting plasma triglyceride significantly declined (29.3%) during
      overfeeding (P < 0.001). In addition, there were no significant changes in
      inflammatory markers. Urine excretion of 4 sugars and polyethylene glycol, used
      as a proxy for gut permeability, and plasma concentration of zonulin, a marker of
      paracellular gut permeability, were unchanged. Moreover, overfeeding was not
      associated with consistent changes in gut microbiota profiles, but marked
      alterations were observed in a subgroup of 6 individuals. Conclusions: Our
      findings suggest that short-term overfeeding with an HFD does not significantly
      impair insulin sensitivity and gut permeability in normal-weight healthy men, and
      that changes in dominant communities of fecal bacteria occur only in certain
      individuals. The study was registered in the German Clinical Trial Register as
      DRKS00006211.

PMID- 29378052
TI  - Soda Intake Is Directly Associated with Serum C-Reactive Protein Concentration in
      Mexican Women.
AB  - Background: Soda intake is associated with an increased risk of cardiovascular
      disease. Consumption of diet sodas, often considered healthy alternatives to
      sodas, could also increase the likelihood of cardiovascular outcomes. Objective:
      This study aims to evaluate the relation between soda and diet soda and
      biomarkers of cardiovascular risk. Methods: We conducted a cross-sectional
      analysis among 825 Mexican women free of diabetes, cardiovascular disease, and
      cancer, and for whom serum concentrations of C-reactive protein (CRP), C-peptide,
      adiponectin, and leptin were available. Mean +/- SD age was 45.9 +/- 6.6 y, the
      majority of women were premenopausal (60.4%), and the prevalence of obesity was
      35%. We estimated the adjusted percentage differences in biomarkers and 95% CIs
      by performing multiple linear regression models comparing categories of
      consumption for soda and diet soda adjusting for age, family history of heart
      disease, menopause, menopausal hormone therapy, socioeconomic status, region,
      smoking, physical activity, alcohol intake, and dietary patterns. Results: In the
      entire study sample we observed a 50% higher serum CRP concentration in women in
      the highest soda intake quartile (median intake: 202.9 mL/d, IQR: 101.4, 304.3
      mL/d) compared to those in the lowest (median intake: 11.8 mL/d, IQR: 0.0, 152.1
      mL/d). After stratification by menopausal status, results remained significant
      only for premenopausal women. Premenopausal women in the highest quartile of soda
      intake had 56% higher CRP concentration relative to women in the lowest quartile.
      We observed no significant association with the other biomarkers. After further
      adjustment for body mass index, a potential mediator, results remained
      significant only for CRP. Diet soda consumption was not associated with any of
      the biomarkers. Conclusions: Consumption of soda was associated with adverse
      levels in a biomarker of inflammation and cardiovascular risk, serum CRP, in
      Mexican women. These results add to the accumulating evidence on soda and
      cardiovascular risk. More research is necessary to understand the potential
      impact of artificially sweetened sodas.

PMID- 29378055
TI  - Fructose Feeding during the Postabsorptive State Alters Body Composition and
      Spares Nitrogen in Protein-Energy-Restricted Old Rats.
AB  - Background: Fructose feeding in the context of high energy intake is recognized
      as being responsible for metabolic dysregulation. However, its consumption in the
      postabsorptive state might contribute to reducing the use of amino acids (AAs) as
      energy substrates and thus spare nitrogen resources, which could be beneficial
      during catabolic states. Objective: We hypothesized that fructose feeding during
      a catabolic situation corresponding to protein-energy restriction (PER) in older
      rats would reduce AA utilization for energy purposes, thus slowing down the loss
      of body weight (BW) and improving body composition. Methods: For 45 d, 22-mo-old
      male Wistar rats (average weight: 716 g) were fed a control ration (13% protein)
      either at normal (20 g/d), restricted (PER: 10 g/d), or at PER levels
      supplemented with glucose (3 g/d) or fructose (3 g/d) and then studied in the
      postabsorptive state. We measured BW, body composition, and enzyme activities and
      metabolite concentrations related to glucose, fructose, and AA metabolism.
      Results: Both glucose and fructose feeding reduced PER-induced loss of BW and
      lean mass (-27% compared with PER), but only fructose reduced the loss of fat
      mass (-28% compared with PER). Fructose feeding prevented the PER-induced loss of
      muscle and intestinal mass. Fructose feeding also reduced circulating branched
      chain AA concentrations by 50% (compared with PER) and increased those of alanine
      (+65% compared with PER). A reduction in hepatic enzymes related to AA catabolism
      was also observed during fructose feeding (compared with PER), whereas glycogen
      concentrations were enhanced in both intestine (+300%) and muscle (+21%).
      Conclusions: We showed that in PER older rats, fructose feeding improved body
      composition and the weight of several organs by reducing AA catabolism and
      utilization for energy production and liver autophagy potential. This could be
      advantageous in sparing body proteins, particularly during catabolic states, such
      as those related to malnutrition during aging.

PMID- 29378054
TI  - RNase H2-Dependent Polymerase Chain Reaction and Elimination of Confounders in
      Sample Collection, Storage, and Analysis Strengthen Evidence That microRNAs in
      Bovine Milk Are Bioavailable in Humans.
AB  - Background: Evidence suggests that dietary microRNAs (miRs) are bioavailable and
      regulate gene expression across species boundaries. Concerns were raised that the
      detection of dietary miRs in plasma might have been due to sample contamination
      or lack of assay specificity. Objectives: The objectives of this study were to
      assess potential confounders of plasma miR analysis and to detect miRs from
      bovine milk in human plasma. Methods: Potential confounders of plasma miR
      analysis (circadian rhythm, sample collection and storage, calibration, and
      erythrocyte hemolysis) were assessed by quantitative reverse transcriptase
      polymerase chain reaction (PCR) by using blood from healthy adults (7 men, 6
      women; aged 23-57 y). Bovine miRs were analyzed by RNase H2-dependent PCR (rhPCR)
      in plasma collected from a subcohort of 11 participants before and 6 h after
      consumption of 1.0 L of 1%-fat bovine milk. Results: The use of heparin tubes for
      blood collection resulted in a complete loss of miRs. Circadian variations did
      not affect the concentrations of 8 select miRs. Erythrocyte hemolysis caused
      artifacts for some miRs if plasma absorbance at 414 nm was >0.300. The stability
      of plasma miRs depended greatly on the matrix in which the miRs were stored and
      whether the plasma was frozen before analysis. Purified miR-16, miR-200c, and cel
      miR-39 were stable for <=24 h at room temperature, whereas losses equaled <=80%
      if plasma was frozen, thawed, and stored at room temperature for as little as 4
      h. rhPCR distinguished between bovine and human miRs with small variations in the
      nucleotide sequence; plasma concentrations of Bos taurus (bta)-miR-21-5p and bta
      miR-30a-5p were >100% higher 6 h after milk consumption than before milk
      consumption. Conclusions: Confounders in plasma miR analysis include the use of
      heparin tubes, erythrocyte hemolysis, and storage of thawed plasma at room
      temperature. rhPCR is a useful tool to detect dietary miRs.

PMID- 29378053
TI  - Lutein Is Differentially Deposited across Brain Regions following Formula or
      Breast Feeding of Infant Rhesus Macaques.
AB  - Background: Lutein, a yellow xanthophyll, selectively accumulates in primate
      retina and brain. Lutein may play a critical role in neural and retinal
      development, but few studies have investigated the impact of dietary source on
      its bioaccumulation in infants. Objective: We explored the bioaccumulation of
      lutein in infant rhesus macaques following breastfeeding or formula-feeding.
      Methods: From birth to 6 mo of age, male and female rhesus macaques (Macaca
      mulatta) were either breastfed (BF) (n = 8), fed a formula supplemented with
      lutein, zeaxanthin, beta-carotene, and lycopene (237, 19.0, 74.2, and 338
      nmol/kg, supplemented formula-fed; SF) (n = 8), or fed a formula with low amounts
      of these carotenoids (38.6, 2.3, 21.5, and 0 nmol/kg, unsupplemented formula-fed;
      UF) (n = 7). The concentrations of carotenoids in serum and tissues were analyzed
      by HPLC. Results: At 6 mo of age, the BF group exhibited significantly higher
      lutein concentrations in serum, all brain regions, macular and peripheral retina,
      adipose tissue, liver, and other tissues compared to both formula-fed groups (P <
      0.001). Lutein concentrations were higher in the SF group than in the UF group in
      serum and all tissues, with the exception of macular retina. Lutein was
      differentially distributed across brain areas, with the highest concentrations in
      the occipital cortex, regardless of the diet. Zeaxanthin was present in all brain
      regions but only in the BF infants; it was present in both retinal regions in all
      groups but was significantly enhanced in BF infants compared to either formula
      group (P < 0.001). beta-Carotene accumulated across brain regions in all groups,
      but was not detected in retina. Although lycopene was found in many tissues of
      the SF group, it was not detected in the brain or retina. Conclusions: Although
      carotenoid supplementation of infant formula significantly increased serum and
      tissue lutein concentrations compared to unsupplemented formula, concentrations
      were still well below those in BF infants. Regardless of diet, occipital cortex
      showed selectively higher lutein deposition than other brain regions, suggesting
      lutein's role in visual processing in early life.

PMID- 29378056
TI  - Lysine Requirements of Healthy Pregnant Women are Higher During Late Stages of
      Gestation Compared to Early Gestation.
AB  - Background: Lysine is the first limiting amino acid in cereal proteins and is
      found mainly in animal-derived products. Current Dietary Reference Intake (DRI)
      recommendations extrapolate lysine requirements during pregnancy from nonpregnant
      adult data, and may underestimate true requirements. Objective: Our objective is
      to define a quantitative lysine requirement in healthy pregnant women and to
      determine whether requirements vary between 2 phases of gestation. Methods:
      Fourteen pregnant women in early (12-19 wk) and 19 women in late (33-39 wk)
      gestation were studied using the indicator amino acid oxidation technique.
      Individual lysine intakes (6-84 mg . kg-1 . d-1, deficient to excess) were tested
      on each study day as a crystalline amino acid mixture based on egg protein
      composition. Isonitrogenous diets maintained protein intake at 1.5 g . kg-1 . d-1
      and calorie intake at 1.7 times resting energy expenditure during each study day.
      Phenylalanine and tyrosine intakes were held constant across all lysine intakes.
      Breath and urine samples were collected at baseline and isotopic steady state.
      Lysine requirements were determined by measuring the oxidation of L-[1-13C]
      phenylalanine to 13CO2 (F13CO2). Biphase linear regression crossover analysis was
      used to determine a breakpoint (which represents the estimated average
      requirement, EAR) in F13CO2. Results: The EAR for lysine during early gestation
      was determined to be 36.6 mg . kg-1 . d-1 (R2 = 0.484, upper 95% CI = 46.2 mg .
      kg-1 . d-1), similar to an earlier adult requirement of 36 mg . kg-1 . d-1. The
      EAR for lysine during late gestation was determined to be 50.3 mg . kg-1 . d-1
      (R2 = 0.664, upper 95% CI = 60.4 mg . kg-1 . d-1), 23% higher than the current
      pregnancy DRI EAR recommendation of 41 mg . kg-1 . d-1. Conclusions: Our results
      suggest that lysine requirements are higher during late gestation compared to
      early gestation, and that current dietary lysine recommendations during late
      stages of pregnancy may be underestimated. The results have implications for
      populations consuming cereal-based diets as their primary source of protein. This
      trial was registered at clinicaltrials.gov as NCT01776931.

PMID- 29378058
TI  - Long-Term Effects of Nutritional Supplementation in Childhood.

PMID- 29378059
TI  - Uptake of Dietary Milk microRNAs by Adult Humans: Rules for the Game of Hide and
      Seek.

PMID- 29378060
TI  - How Does Breast Milk Enhance Lutein Absorption?

PMID- 29378061
TI  - Young Adult Outcomes for Children With 22q11 Deletion Syndrome and Comorbid ADHD.
AB  - Background: 22q11.2 deletion syndrome (22q11DS) is a common microdeletion
      syndrome associated with a variety of negative health, cognitive, emotional, and
      behavioral outcomes. 22q11DS is comorbid with many psychiatric disorders
      including attention-deficit/hyperactivity disorder (ADHD). The current study
      aimed to investigate the cognitive, behavioral, and functional outcomes that a
      childhood ADHD diagnosis predicts to in adulthood. Methods: This longitudinal
      study followed 52 individuals with 22q11DS over 9 years. Childhood ADHD was
      operationalized both categorically (Diagnostic and statistical manual - 4th
      edition (DSM-IV) ADHD diagnoses) and dimensionally (inattentive and hyperactive
      impulsive symptoms) and was tested as predictors of young adult outcomes.
      Results: As young adults, children with 22q11DS + baseline ADHD had more parent
      reported executive dysfunction and lower levels of clinician-rated overall
      functioning than those with 22q11DS yet without ADHD. Dimensional symptoms of
      ADHD in childhood did not predict young adult outcomes. No self-report
      differences emerged between those with and without baseline ADHD. The majority
      (82.4%) of individuals with 22q11DS + baseline ADHD were never treated with an
      ADHD medication. Conclusions: A categorical diagnosis of ADHD in childhood
      predicted a greater variety of worse outcomes than dimensional levels of ADHD
      symptoms. Despite the significant impact of comorbid ADHD in 22q11DS, evidence
      based treatment rates were low.

PMID- 29378062
TI  - Medication class enrichment analysis: a novel algorithm to analyze multiple
      pharmacologic exposures simultaneously using electronic health record data.
AB  - Objective: Observational studies analyzing multiple exposures simultaneously have
      been limited by difficulty distinguishing relevant results from chance
      associations due to poor specificity. Set-based methods have been successfully
      used in genomics to improve signal-to-noise ratio. We present and demonstrate
      medication class enrichment analysis (MCEA), a signal-to-noise enhancement
      algorithm for observational data inspired by set-based methods. Materials and
      Methods: We used The Health Improvement Network database to study medications
      associated with Clostridium difficile infection (CDI). We performed case-control
      studies for each medication in The Health Improvement Network to obtain odds
      ratios (ORs) for association with CDI. We then calculated the association of each
      pharmacologic class with CDI using logistic regression and MCEA. We also
      performed simulation studies in which we assessed the sensitivity and specificity
      of logistic regression compared to MCEA for ORs 0.1-2.0. Results: When analyzing
      pharmacologic classes using logistic regression, 47 of 110 pharmacologic classes
      were identified as associated with CDI. When analyzing pharmacologic classes
      using MCEA, only fluoroquinolones, a class of antibiotics with biologically
      confirmed causation, and heparin products were associated with CDI. In
      simulation, MCEA had superior specificity compared to logistic regression across
      all tested effect sizes and equal or better sensitivity for all effect sizes
      besides those close to null. Discussion: Although these results demonstrate the
      promise of MCEA, additional studies that include inpatient administered
      medications are necessary for validation of the algorithm. Conclusions: In
      clinical and simulation studies, MCEA demonstrated superior sensitivity and
      specificity for identifying pharmacologic classes associated with CDI compared to
      logistic regression.

PMID- 29378063
TI  - PHASE DEPENDENT OPTICALLY STIMULATED LUMINESCENCE IN CU-DOPED Sr4Si3O8Cl4.
AB  - Phase dependent optically stimulated luminescence (OSL) is studied in Cu-doped
      Sr4Si3O8Cl4. The Study shows that samples in which amount of contributing
      strontium metasilicate phase in Cu-doped Sr4Si3O8Cl4 is less, show intense OSL
      while those samples in which strontium metasilicate phase is more show weak OSL.
      The observed Cu luminescence is also found to be phase dependent. Sample in which
      Sr4Si3O8Cl4 phase is dominant, the observed Cu luminescence is around 350 nm
      whereas an additional longer wavelength band around 450 nm is observed when the
      strontium metasilicate phase is present in significant amount. The relatively
      phase pure, Cu-doped Sr4Si3O8Cl4 shows good OSL properties. The sensitivity of
      such material is 3.89 times more compared to commercial Al2O3:C (Landauer Inc.).
      High sensitivity, good linearity and reusability, along with low fading make this
      material as good OSL phosphor and may find applications in OSL based radiation
      dosimetry.

PMID- 29378064
TI  - PERFORMANCE OF THE VARSKIN 5 (v5.3) ELECTRON DOSIMETRY MODEL.
AB  - A new electron skin dosimetry model was developed for the VARSKIN 5 tissue
      dosimetry code. This model employs energy deposition kernels that provides for
      improved accuracy of energy deposition at the end of electron tracks. The Monte
      Carlo code EGSnrc was utilized to develop these energy deposition kernels such
      that scaling of electron energy loss is dependent on effective atomic number and
      density of the source material, electron range and conservation of energy. This
      work contrasts VARSKIN's electron dosimetry model to several existing
      deterministic and Monte Carlo dosimetry tools to determine the efficacy of these
      improvements. Comparison results are given for a wide range of scenarios that
      extend beyond the typical use of VARSKIN, including mono-energetic electrons and
      a homogenous water medium. For planar and point sources in contact with the skin,
      VARSKIN produces results equated to other dosimetry methods within 10%. However,
      it appears that VARSKIN is unable to account accurately for electron energy loss
      with the introduction of a cover material or an air gap. The comparisons herein
      confirm that VARSKIN provides accurate electron dose calculations for skin
      contamination scenarios.

PMID- 29378065
TI  - Genome-wide association study uncovers a novel QTL allele of AtS40-3 that affects
      the sex ratio of cyst nematodes in Arabidopsis.
AB  - Plant-parasitic cyst nematodes are obligate sedentary parasites that infect the
      roots of a broad range of host plants. Cyst nematodes are sexually dimorphic, but
      differentiation into male or female is strongly influenced by interactions with
      the host environment. Female populations typically predominate under favorable
      conditions, whereas male populations predominate under adverse conditions. Here,
      we performed a genome-wide association study (GWAS) in an Arabidopsis diversity
      panel to identify host loci underlying variation in susceptibility to cyst
      nematode infection. Three different susceptibility parameters were examined, with
      the aim of providing insights into the infection process, the number of females
      and males present in the infected plant, and the female-to-male sex ratio. GWAS
      results suggested that variation in sex ratio is associated with a novel
      quantitative trait locus allele on chromosome 4. Subsequent candidate genes and
      functional analyses revealed that a senescence-associated transcription factor,
      AtS40-3, and PPR may act in combination to influence nematode sex ratio. A
      detailed molecular characterization revealed that variation in nematode sex ratio
      was due to the disturbed common promoter of AtS40-3 and PPR genes. Additionally,
      single nucleotide polymorphisms in the coding sequence of AtS40-3 might
      contribute to the natural variation in nematode sex ratio.

PMID- 29378066
TI  - Free and bound cortisol in plasma and saliva during ACTH challenge in dairy cows
      and horses.
AB  - Cortisol levels reflect hypothalamic-pituitary-adrenocortical (HPA) axis
      activity. While most plasma cortisol is supposed to be bound to the soluble
      corticosteroid-binding globulin (CBG), only free cortisol (FC) actively regulates
      metabolic and immunological processes. We aimed to establish a multispecies
      suitable method to assess FC in cows and horses which in combination with total
      cortisol (TC) allows interpreting proportional changes of cortisol in saliva as
      well as in blood in response to a standardized HPA axis activation via ACTH. We
      further investigated if the ratios of cortisol fractions as obtained at basal
      levels in healthy horses (herbivorous and monogastric) and dairy cows
      (herbivorous and ruminant) change during HPA axis activation, and to which extent
      saliva cortisol (SC) is representative for alterations in plasma FC and adrenal
      cortex reactivity. However, it was not the objective of the present study to
      directly compare the two species. Dosages of ACTH applied in cows and horses were
      based on published data. Synthetic ACTH was intravenously administered to eight
      dairy cows (0.16 ug/kg BW) and five horses (1 ug/kg BW). Blood and saliva were
      collected every 30 min for 3 h from a jugular vein catheter, and analyzed for TC
      and SC, the ratio of free cortisol (rFC), and the concentration of FC (cFC) in
      plasma. During the entire sampling period of the ACTH test, plasma TC was
      paralleled by blood cFC, rFC, and SC in both cows and horses. All cortisol
      fractions increased within 30 min of ACTH administration compared to basal values
      (0 min, P < 0.05). Peak TC concentration reached 63.2 +/- 9.6 ng/mL and 73.2 +/-
      11.8 ng/mL in bovine and equine plasma, respectively. Peak values of rFC averaged
      17.9 +/- 4.5% in cows and 19.2 +/- 7.8% in horses. The ratio of SC to cFC in
      horses remained similar during the ACTH challenge suggesting that SC is recruited
      from plasma FC. However, SC increased less compared to plasma TC and FC during
      HPA axis activation in cows. In conclusion, the short-term activation of the HPA
      axis caused not only an elevation of TC, but also a similar increase of rFC in
      both species. SC closely reflected changes of FC in horses, but less accurately
      in cows. The concomitant evaluation of changes among cortisol fractions might
      give further indications on adaptation mechanisms in glucocorticoid regulation as
      well as differentiate cortisol-related health disorders.

PMID- 29378067
TI  - Associations of polymorphisms in the cytokine genes IL1beta (rs16944), IL6
      (rs1800795), IL12b (rs3212227) and growth factor VEGFA (rs2010963) with
      anthracosilicosis in coal miners in Russia and related genotoxic effects.
AB  - Anthracosilicosis (AS), a prevalent form of pneumoconiosis among coal miners,
      results from the accumulation of carbon and silica in the lungs from inhaled coal
      dust. This study investigated genotoxic effects and certain cytokine genes
      polymorphic variants in Russian coal miners with AS. Peripheral leukocytes were
      sampled from 129 patients with AS confirmed by X-ray and tissue biopsy and from
      164 asymptomatic coal miners. Four single-nucleotide polymorphisms were genotyped
      in the extracted DNA samples: IL1beta T-511C (rs16944), IL6 C-174G (rs1800795),
      IL12b A1188C (rs3212227) and VEGFA C634G (rs2010963). Genotoxic effects were
      assessed by the analysis of chromosome aberrations in cultured peripheral
      lymphocytes. The mean frequency of chromatid-type aberrations and chromosome-type
      aberrations, namely, chromatid-type breaks and dicentric chromosomes, was found
      to be higher in AS patients [3.70 (95% confidence interval {CI}, 3.29-4.10) and
      0.28 (95% CI, 0.17-0.38)] compared to the control group [2.41 (95% CI, 2.00-2.82)
      and 0.09 (95% CI, 0.03-0.15)], respectively. IL1beta gene T/T genotype (rs16944)
      was associated with AS [17.83% in AS patients against 4.35% in healthy donors,
      odds ratio = 4.77 (1.88-12.15), P < 0.01]. A significant increase in the level of
      certain chromosome interchanges among AS donors is of interest because such
      effects are typical for radiation damage and caused by acute oxidative stress.
      IL1beta T allele probably may be considered as an AS susceptibility factor among
      coal miners.

PMID- 29378068
TI  - MONTE CARLO SIMULATIONS OF SPATIAL LET DISTRIBUTIONS IN CLINICAL PROTON BEAMS.
AB  - The linear energy transfer (LET) is commonly used as a parameter which describes
      the quality of the radiation applied in radiation therapy with fast ions. In
      particular in proton therapy, most models which predict the radiobiological
      properties of the applied beam, are fitted to the dose-averaged LET, LETd. The
      related parameter called the fluence- or track-averaged LET, LETt, is less
      frequently used. Both LETt and in particular LETd depends profoundly on the
      encountered secondary particle spectrum. For proton beams including all secondary
      particles, LETd may reach more than 3 keV/um in the entry channel of the proton
      field. However, typically the charged particle spectrum is only averaged over the
      primary and secondary protons, which is in the order of 0.5 keV/um for the same
      region. This is equal to assuming that the secondary particle spectrum from
      heavier ions is irrelevant for the resulting radiobiology, which is an assertion
      in the need of closer investigation. Models which rely on LETd should also be
      clear on what type of LETd is used, which is not always the case. Within this
      work, we have extended the Monte Carlo particle transport code SHIELD-HIT12A to
      provide dose- and track-average LET-maps for ion radiation therapy treatment
      plans.

PMID- 29378070
TI  - From the Cover: Inhibitors of Nicotinamide Phosphoribosyltransferase Cause
      Retinal Damage in Larval Zebrafish.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) has been investigated as a target
      for oncology because it catalyzes a rate-limiting step in cellular energy
      metabolism to produce nicotinamide adenine dinucleotide. Small molecule
      inhibitors of NAMPT have been promising drug candidates but preclinical
      development has been hindered due to associated retinal toxicity. Here we
      demonstrate that larval zebrafish can predict retinal toxicity associated with
      this mechanism revealing an attractive alternative method for identifying such
      toxicities. Zebrafish permit higher throughput testing while using far lower
      quantities of test article compared with mammalian systems. NAMPT inhibitor
      associated toxicity manifested in zebrafish as a loss of response to visual cues
      compared with auditory cues. Zebrafish retinal damage associated with NAMPT
      inhibitor treatment was confirmed through histopathology. Ranking 6 NAMPT
      inhibitors according to their impact on zebrafish vision revealed a positive
      correlation with their in vitro potencies on human tumor cells. This correlation
      indicates translatable pharmacodynamics between zebrafish and human NAMPT and is
      consistent with on-target activity as the cause of retinal toxicity associated
      with NAMPT inhibition. Together, these data illustrate the utility of zebrafish
      for identifying compounds that may cause ocular toxicity in mammals, and,
      likewise, for accelerating development of compounds with improved safety margins.

PMID- 29378069
TI  - The Impact of Novel Assessment Methodologies in Toxicology on Green Chemistry and
      Chemical Alternatives.
AB  - The field of experimental toxicology is rapidly advancing by incorporating novel
      techniques and methods that provide a much more granular view into the mechanisms
      of potential adverse effects of chemical exposures on human health. The data from
      various in vitro assays and computational models are useful not only for
      increasing confidence in hazard and risk decisions, but also are enabling better,
      faster and cheaper assessment of a greater number of compounds, mixtures, and
      complex products. This is of special value to the field of green chemistry where
      design of new materials or alternative uses of existing ones is driven, at least
      in part, by considerations of safety. This article reviews the state of the
      science and decision-making in scenarios when little to no data may be available
      to draw conclusions about which choice in green chemistry is "safer." It is clear
      that there is no "one size fits all" solution and multiple data streams need to
      be weighed in making a decision. Moreover, the overall level of familiarity of
      the decision-makers and scientists alike with new assessment methodologies, their
      validity, value and limitations is evolving. Thus, while the "impact" of the new
      developments in toxicology on the field of green chemistry is great already, it
      is premature to conclude that the data from new assessment methodologies have
      been widely accepted yet.

PMID- 29378071
TI  - A Farewell to Harms: The Audacity to Design Safer Products.

PMID- 29378072
TI  - Person-Centered Care for LGBT Older Adults.

PMID- 29378076
TI  - Management of Dissociated Vertical Deviation.

PMID- 29378075
TI  - Evidence-Based Practice Guideline: Delirium.
AB  - Delirium is a common cause of morbidity and mortality in hospitalized older
      adults often superimposed on dementia. Older patients with delirium are more
      likely than other populations to develop hospital-acquired infections, pressure
      ulcers, and immobility and nutritional issues, as well as to have increased
      health care costs, longer hospital stays, and long-term care following discharge.
      Interventions that prevent or mitigate the effects of delirium while promoting
      recovery are essential for caring for hospitalized older patients. This article
      is a summary of an evidence-based guideline that includes a framework for
      addressing delirium that focuses on predisposing and precipitating factors for
      delirium. In addition, the guideline includes evidence-based assessment and
      intervention principles, along with a review of reliable and valid assessment
      instruments. The guideline also identifies measurable outcomes for managing
      delirium and a quality improvement approach for improving outcomes. [Journal of
      Gerontological Nursing, 44(2), 14-24.].

PMID- 29378077
TI  - "My Baby's Right Eye Is Red".

PMID- 29378078
TI  - The Roundabout Way of Finding the Right Target.

PMID- 29378079
TI  - Treatment of Small Angle Hypertropia With Inferior Oblique Overaction.

PMID- 29378080
TI  - Erratum for "Comparison of Minimally Invasive Strabismus (MISS) and Conventional
      Strabismus Surgery Using the Limbal Approach".

PMID- 29378081
TI  - Pediatric Infectious Endophthalmitis: A Case Series.

PMID- 29378082
TI  - 2017 Reviewers.

PMID- 29378083
TI  - Torpedo Maculopathy.

PMID- 29378085
TI  - Direct Reductive N-Functionalization of Aliphatic Nitro Compounds.
AB  - The first general protocol for the direct reductive N-functionalization of
      aliphatic nitro compounds is presented. The nitro group is partially reduced to a
      nitrenoid, with a mild and readily available combination of B2 pin2 and zinc
      organyls. Thereby, the formation of an unstable nitroso intermediate is avoided,
      which has so far severely limited reductive transformations of aliphatic nitro
      compounds. The reaction is concluded by an electrophilic amination of zinc
      organyls.

PMID- 29378084
TI  - Pregnancy Weight Gain by Gestational Age in Women with Uncomplicated Dichorionic
      Twin Pregnancies.
AB  - BACKGROUND: Twin pregnancies are at increased risk for adverse outcomes and are
      associated with greater gestational weight gain compared to singleton
      pregnancies. Studies that disentangle the relationship between gestational
      duration, weight gain and adverse outcomes are needed to inform weight gain
      guidelines. We created charts of the mean, standard deviation and select
      percentiles of maternal weight gain-for-gestational age in twin pregnancies and
      compared them to singleton curves. METHODS: We abstracted serial prenatal weight
      measurements of women delivering uncomplicated twin pregnancies at Magee-Womens
      Hospital (Pittsburgh, PA, 1998-2013) and merged them with the hospital's
      perinatal database. Hierarchical linear regression was used to express pregnancy
      weight gain as a smoothed function of gestational age according to pre-pregnancy
      BMI category. Charts of week- and day-specific values for the mean, standard
      deviation, and percentiles of maternal weight gain were created. RESULTS:
      Prenatal weight measurements (median: 11 [interquartile range: 9, 13] per woman)
      were available for 1109 women (573 normal weight, 287 overweight, and 249 obese).
      The slope of weight gain was most pronounced in normal weight women and flattened
      with increasing pre-pregnancy BMI (e.g. 50th percentiles of 6.8, 5.7, and 3.6 kg
      at 20 weeks and 19.8, 18.1, and 14.4 at 37 weeks in normal weight, overweight,
      and obese women, respectively). Weight gain patterns in twins diverged from
      singletons after 17-19 weeks. CONCLUSIONS: Our charts provide a tool for the
      classification of maternal weight gain in twin pregnancies. Future work is needed
      to identify the range of weight gain associated with optimal pregnancy health
      outcomes.

PMID- 29378086
TI  - Transient-Ligand-Enabled ortho-Arylation of Five-Membered Heterocycles: Facile
      Access to Mechanochromic Materials.
AB  - Reported herein is the first example of a direct arylation of heteroarenes by a
      transient-ligand-directed strategy without the need to construct and deconstruct
      the directing group. A wide range of heteroarenes undergoes the coupling with
      diverse aryl iodides to assemble a large library of highly selective and
      functionalized 3-arylthiophene-2-carbaldehydes. This route provides an
      opportunity to rapidly access new mechanofluorochromic materials. Moreover, a
      novel strategy for mechanochromic luminogens with chromism trends of red- and
      blue-shifts has been disclosed for the first time by facile functional-group
      modifications to a common structural core.

PMID- 29378087
TI  - Advances in ginsenoside biosynthesis and metabolic regulation.
AB  - In this paper, we reviewed the advances in ginsenoside biosynthesis and metabolic
      regulation. To begin with, the application of elicitors in the ginsenoside
      biosynthesis was discussed. Methyl jasmonate (MJ) and analogues have the best
      effect on accumulation of ginsenoside compared with other elicitors, and few
      biotic elicitors are applied in Panax genus plants tissue culture. In addition,
      so far, more than 40 genes encoding ginsenoside biosynthesis related enzymes have
      been cloned and identified from Panax genus, such as UDP-glycosyltransferases
      (UGT) genes UDPG, UGTAE2, UGT94Q2, UGTPg100, and UGTPg1. However, the downstream
      pathway of the ginsenoside biosynthesis is still not clear. Moreover, some
      methods have been used to increase the expression of functional genes and
      ginsenoside content in the ginsenoside synthesis pathway, including elicitors,
      overexpression, RNAi, and transcription factors. The ginsenoside biosynthesis
      pathway should be revealed so that ginsenoside contents can be regulated.

PMID- 29378088
TI  - Reversible Redox Chemistry of Azo Compounds for Sodium-Ion Batteries.
AB  - Sustainable sodium-ion batteries (SSIBs) using renewable organic electrodes are
      promising alternatives to lithium-ion batteries for the large-scale renewable
      energy storage. However, the lack of high-performance anode material impedes the
      development of SSIBs. Herein, we report a new type of organic anode material
      based on azo group for SSIBs. Azobenzene-4,4'-dicarboxylic acid sodium salt is
      used as a model to investigate the electrochemical behaviors and reaction
      mechanism of azo compound. It exhibits a reversible capacity of 170 mAh g-1 at
      0.2C. When current density is increased to 20C, the reversible capacities of 98
      mAh g-1 can be retained for 2000 cycles, demonstrating excellent cycling
      stability and high rate capability. The detailed characterizations reveal that
      azo group acts as an electrochemical active site to reversibly bond with Na+ .
      The reversible redox chemistry between azo compound and Na ions offer
      opportunities for developing long-cycle-life and high-rate SSIBs.

PMID- 29378089
TI  - Impaired sperm function in infertile men relies on the membrane sterol pattern.
AB  - Membrane cholesterol removal appears a key step for the gain of fertility
      potential during sperm maturation. However, the membrane sterol pattern in sperm
      cells from infertile patients, with impaired sperm parameters, has been poorly
      investigated. To elucidate a causative link between sperm membrane composition in
      male fertility, here we have investigated the levels of cholesterol and its
      oxidized derivatives 7beta-hydroxycholesterol and 7-keto-cholesterol in sixteen
      infertile patients with oligo-asthenozoospermia and 16 normozoospermic (N)
      fertile subjects. Furthermore, ten of 16 N fertile subjects agreed to receive a
      defined testicular thermal challenge by adhering to a programme of sauna sessions
      for 1 month. Semen samples were obtained from each of the participants, and sperm
      parameters were assessed according to the World Health Organization criteria.
      Sperm levels of cholesterol, 7beta-hydroxycholesterol and 7-keto-cholesterol were
      quantified by ultra-pressure liquid chromatography mass spectrometry. The results
      showed that oligo-asthenozoospermia patients had a huge amount of cholesterol
      content compared with fertile subjects (12.40 +/- 6.05 MUg/106 cells vs. 0.45 +/-
      0.28 MUg/106 cells, p < 0.001, N and oligo-asthenozoospermia, respectively).
      Also, oxidized derivatives were significantly higher in oligo-asthenozoospermia
      patients (7beta-hydroxycholesterol: 1.96 +/- 1.03 ng/106 cells vs. 0.075 +/- 0.05
      ng/106 cells, p < 0.001 and 7-keto-cholesterol: 1.11 +/- 0.72 ng/106 cells vs.
      0.005 +/- 0.003 ng/106 cells, p < 0.001). Moreover, sauna exposure, in parallel
      with a progressive worsening of sperm motility parameters, was associated with a
      reversible increase in sperm cholesterol after the third and fourth week of
      treatment, whilst 7beta-hydroxycholesterol and 7-keto-cholesterol levels showed
      an earlier enhancement starting from the second week. Our data show for the first
      time in humans a strong difference in the cholesterol and its oxidized
      derivatives of infertile and fertile subjects. These findings suggest a strict
      biochemical link relating testis function, sperm membrane status and male
      fertility potential.

PMID- 29378090
TI  - A Chimeric Styrene Monooxygenase with Increased Efficiency in Asymmetric
      Biocatalytic Epoxidation.
AB  - The styrene monooxygenase (SMO) system from Pseudomonas sp. consists of two
      enzymes (StyA and StyB). StyB catalyses the reduction of FAD at the expense of
      NADH. After the transfer of FADH2 from StyB to StyA, reaction with O2 generates
      FAD-OOH, which is the epoxidising agent. The wastage of redox equivalents due to
      partial diffusive transfer of FADH2 , the insolubility of recombinant StyB and
      the impossibility of expressing StyA and StyB in a 1:1 molar ratio reduce the
      catalytic efficiency of the natural system. Herein we present a chimeric SMO (Fus
      SMO) that was obtained by genetic fusion of StyA and StyB through a flexible
      linker. Thanks to a combination of: 1) balanced and improved expression levels of
      reductase and epoxidase units, and 2) intrinsically higher specific epoxidation
      activity of Fus-SMO in some cases, Escherichia coli cells expressing Fus-SMO
      possess about 50 % higher activity for the epoxidation of styrene derivatives
      than E. coli cells coexpressing StyA and StyB as discrete enzymes. The
      epoxidation activity of purified Fus-SMO was up to three times higher than that
      of the two-component StyA/StyB (1:1, molar ratio) system and up to 110 times
      higher than that of the natural fused SMO. Determination of coupling efficiency
      and study of the influence of O2 pressure were also performed. Finally, Fus-SMO
      and formate dehydrogenase were coexpressed in E. coli and applied as a self
      sufficient biocatalytic system for epoxidation on greater than 500 mg scale.

PMID- 29378092
TI  - NGWA News.

PMID- 29378091
TI  - Epoxy-Functionalized Porous Organic Polymers via the Diels-Alder Cycloaddition
      Reaction for Atmospheric Water Capture.
AB  - The synthesis of highly microporous, epoxy-functionalized porous organic polymers
      (ep-POPs) by a one-pot, catalyst-free Diels-Alder cycloaddition polymerization is
      reported. The high oxygen content of ep-POPs offer efficient hydrogen-bonding
      sites for water molecules, thus leading to high water-uptake capacities up to
      39.2-42.4 wt % under a wide temperature range of 5-45  degrees C, which covers
      the span of climatic conditions and manufacturing applications in which such
      materials might be used. Importantly, ep-POPs demonstrated regeneration
      temperatures as low as 55  degrees C, as well as excellent water stability,
      recyclability, and high specific surface areas up to 852 m2  g-1 .

PMID- 29378093
TI  - Erratum.

PMID- 29378094
TI  - [Effect of minor bioactive food substances - rutin and hesperidin in their
      separate and combined alimentary arrives on the immune system of rats and the
      activity of nuclear factor NF-kB liver cells].
AB  - The effect of rutin and hesperidin in their separate and combined admission to
      the immune system and the activity of nuclear factor NF-kB of rat liver cells has
      been investigated. Wistar male rats with an initial body weight of 224-225 g were
      divided into 4 groups of 6 rats in each. The rats of the 1st group (control)
      received a complete semi-synthetic diet, rats in group 2 - the same diet
      supplemented with rutine (400 mg/kg b.w.); the rats of group 3 - with the
      addition of hesperidin (400 mg/kg bw); group 4 - with the addition of rutin and
      hesperidin (400 mg/kg b.w. each) for 14 days. Animals received feed in free
      access mode in an amount of 25-30 g per rat per day, that corresponded to 15 g of
      dry formula. Animals received water also in free access. It has been found that
      rutin and hesperidin, included in the diet of rats both alone (groups 2 and 3)
      and together (group 4), have immunomodulatory impact which is a reduce of
      lymphocyte relative content [1st gr. - 70.55+/-1.58%, 2nd gr. - 63.62+/-2.85%,
      3rd gr. - 62.03+/-3.16% (p1-3<0.05), 4th gr. - 65.75+/-1.08% (p1-4<0.05)] and an
      increase of percentage of neutrophil leukocytes [1st gr - 19.98+/-0.97%, 2nd gr. 
      25.35+/-3.14%, 3rd gr. - 28.27+/-3.30% (p1-3<0.05), 4th gr. - 24.15+/-1.52% (p1
      4<0.05)] and NK-cells in the peripheral blood [1st gr. - 3.29+/-0.45%, 2nd gr. -
      6.91+/-0.70% (p1-2<0.05), 3rd gr. - 5.88+/-0.79% (p1-3<0.05), 4th gr. - 4.64+/
      0.32% (p1-4<0.05)], that can be considered as a shift in the direction of innate
      immunity factors.In addition, the combined effect of high doses of rutin and
      hesperidin led to a change in erythrocyte parameters: an increase in the average
      volume of red blood cells [1st gr. - 56.00+/-1.06 fl, 2nd gr. - 56.67+/-0.42 fl,
      3rd gr. - 58.50+/- 0.99 fl, 4th gr. - 59.50+/-0.99 fl (p1-4<0.05)], and the
      average content of hemoglobin [1st gr. - 18.97+/-0.45 pg, 2nd gr. - 19.10+/-0.19
      pg, 3rd gr. - 19.73+/- 0.32 pg, 4th gr. - 20.08+/-0.33 pg (p1-4=0.07)], as well
      as increase in the level of TGF-beta1 in peripheral blood [1st gr. - 15.55+/-2.13
      ng/ml, 2nd gr. - 14.81+/- 2.36 ng/ml, 3rd gr. - 17.02+/-2.53 ng/ml, 4th gr. -
      22.14+/-2.29 ng/ml (p1-4<0.05)] and the expression of nuclear factor NF-kB in the
      liver cells [1st gr. - 16.10+/- 0.60 ng/ml; 2nd gr. - 15.14+/-2.28 ng/ml; 3rd gr.
      - 15.85+/-2.09 ng/ml; 4th gr. - 20.49+/-1.68 ng/ml (p1-4<0.05)].

PMID- 29378095
TI  - [Assessment of the impact of vitamin and dietary fiber content in the diet on the
      characteristics of protective colon microbiota populations of rats].
AB  - The content of lactobacilli and enterobacteria in the experiment in rats with
      varying levels of vitamins and dietary fiber was studied. The study was performed
      on 48 male weanling Wistar rats randomized into 8 groups, with the creation of
      vitamin deficiency (30 d.) and its further compensation (5 d.). Vitamin content
      in the semisynthetic diet in rats of the control group N 1 corresponded to 100%
      of a daily adequate intake. In the similar composition of the diet of the control
      group N 2 wheat bran was added in amount of 5% of the weight of the diet. In
      groups N 3-8 rats received a diet with the reduced amount of vitamin mixture by 5
      times (20% of the adequate intake) and the total exclusion of tocopherol,
      thiamine and riboflavin from the mixture. The wheat bran (5% of diet mass) was
      added to the diets in Groups N 4, 6, 8. At the stage of compensation of
      deficiency rats were fed with the diets with increased content of vitamin
      mixture: Group 5-6 to 80% 7-8 to 200% (100 and 220% of the adequate intake,
      respectively), and the groups N 3-4 continued to receive deficient diet with or
      without wheat bran until the end of the experiment. After 35 days rats were
      anesthetized with ether, decapitated, necropsied and the cecum segments were
      selected for quantitative microbiological analysis of its contents.It has been
      shown that the addition of wheat bran to vitamin deficient diet lead to the
      reduction of the manifestation of physical sign of hypovitaminosis. It also
      eliminated the differences in the integrated index of growth and development of
      rats in comparison with the group without vitamin deficiency. It was found that
      the vitamin deficiency in the diet, regardless of the presence or absence of
      wheat bran, led to a significant reduction of the number of lactobacilli in the
      intestinal contents, but almost did not affect the number of normal and
      opportunistic pathogenic enterobacteria. The compensation of deficiency during 5
      days lead to the increased number of lactobacilli, but the physiological levels
      and levels in control animals it reached only in rats received 220% of the
      vitamins with the addition of wheat bran. In the lactobacilli population in all
      rats received different doses of vitamins (including reduced to 20%), regardless
      of the presence of wheat bran, prevailing culturable representatives were 3 kinds
      of Lactobacillus spp. - acidophilus, fermentum, paracasei. These species showed
      stable presence in the intestine even in conditions of prolonged vitamin
      deficiency (35 days).L. acidophilus was the dominated lactoflora representative
      in all rats, its' content was average 91.7% of all culturable lactobacilli. With
      less constancy and in lower amounts were detected L. plantarum and
      representatives of coccal flora (Leuconostoc lactis, Lactococcus lactis).

PMID- 29378096
TI  - [Impact of streptozotocininduced hyperglycemia on anxiety level and physical
      fatigue of Wistar rats].
AB  - The aim of the study was to evaluate type 2 diabetes medicamental biomodel in 70
      days experiment. Control group animals were provided with water ad libitum
      throughout the experiment, experimental group animals for the first two weeks
      were provided with 20% solution of fructose ad libitum instead of water. On the
      15th day, experimental group animals (average body weight 257+/-8 g) were
      injected abdominally with streptozotocin (STZ) in dosage 40 mg/kg of body weight.
      For the next three weeks on the 22nd, 28th and 36th days, glucose level in blood
      taken from the tail vein was measured using portable electrochemical glucometer.
      On the 37th day animals with blood glucose level 11.0 mmol/L or higher were
      included in experimental group for further research. On the 44th and 60th day
      control measurements of glucose level were conducted. On the 70th day animals
      were taken out of experiment by decapitation under ether anesthesia.The
      concentration of glucose, glycosylated hemoglobin, triglycerides, cholesterine,
      HLD and LDL were measured in blood serum. Additionally anxiety level of animals
      was evaluated before and after STZ injection using Elevated plusmaze.The
      comparison of physical fatigue of control and experimental groups was performed
      using treadmill. On the 37th day blood glucose concentration of control group
      animals was 6.6+/-0.4 mmol/L. 33% of animals (13 of 40) with glucose level 11.0
      mmol/L or higher formed the experimental group (average glucose level 16.2+/-1.3
      mmol/L), other 27 rats had normal glucose level. The anxiety level of diabetic
      rats was higher than in control group. Diabetic rats showed significantly lower
      physical fatigue than control rats. On the 44th and 60th day of experiment
      glucose level in experimental rats from group 2 (15.5+/-1.4 i 14.8+/-1.2 mmol/L)
      was significantly higher than of control animals (7.0+/-0.5 i 6.8+/-0.3 mmol/L).
      Glycated hemoglobin level in blood serum of diabetic group (7.2+/-0.7%) was
      significantly higher than of control group (3.3+/-0.2%). This proves the
      progression of stable long-term hyperglycemia. According to results represented
      model can be used for initial experimental evaluation of tested antidiabetic
      biologically active substances.

PMID- 29378097
TI  - [Toxicological evaluation of nanosized colloidal silver, stabilized with
      polyvinylpyrrolidone. I. Characterization of nanomaterial, integral,
      hematological parameters, level of thiol compounds and liver cell apoptosis].
AB  - Nano-sized colloidal silver (NCS) is currently one of the most widely used
      nanomaterials in medicine and consumer's products. Nanoparticles (NPs) of silver,
      in addition to the direct exposition through products may expose human via
      various environmental objects. The aim of the study is to assess the safe doses
      of silver NP received orally. The investigated NCS contained silver NPs with
      diameter of 10-60 nm, predominantly with a nearly spherical form stabilized with
      polyvinylpyrrolidone (PVP). The experiment was performed during 92 days in 5
      groups of male Wistar rats (n=15 in each group), receiving a balanced
      semisynthetic diet. Animal of group 1 (control) received vehicle (deionized
      water) intragastrically for 30 days and then with food, groups from 2nd to 4th -
      PVP and groups from 3rd to 5th NCS, in doses respectively, 0.1; 1.0 and 10 mg/kg
      body weight (b.w.) in terms of silver. The dose of PVP in groups from 2nd to 5th
      did not differ, amounting to 200 mg/kg b.w. During the experiment, the weight
      gain, skin condition, activity, stool, cognitive function were assessed. At the
      end of the feeding period weight of internal organs, intestinal wall permeability
      to protein macromolecules, liver thiols, standard values of blood erythrocytes,
      leukocytes and platelets, hepatocyte apoptosis by flow cytometry were studied.
      These results suggest that in terms of weight gain, lung relative mass, average
      erythrocyte volume, hemoglobin content and concentration in erythrocytes, the
      relative proportion of lymphocytes and neutrophils adverse changes have been
      observed at a dose of 10 mg NPs per kg of b.w. At lower levels of exposure (0.1
      and 1.0 mg/kg b.w.) some specific changes were also observed (in terms of thiols
      pool in liver, cognitive function, relative abundance of monocytes, the number of
      dead hepatocytes), which, however, did not possess an unambiguous dependence on
      the dose. Possible mechanisms of the toxic action of the NCS have been discussed.

PMID- 29378098
TI  - [Actual nutrition of patients suffered from hemorrhagic fever with renal
      syndrome].
AB  - The aim of the article is to study actual ration of patients suffered from
      hemorrhagic fever with renal syndrome (HFRS) and its interaction with the
      development of arterial hypertension (AH). 296 men aged 20-59 suffered from HFRS
      were under the care of physician within the period of 1 to 6 years. Among this
      group 49 cases of arterial hypertension have been registered after HFRS.
      Frequency method of food product consumption was used to define nutrition. A
      Russian questionnaire published by Institute of Nutrition (1997) was used. Actual
      nutrition in men suffered from HFRS is marked by basic nutrients unbalance that
      is: excessive cholesterol and fat consumption (due to saturated fatty acid),
      polyunsaturated fatty acid deficiency, sugar overuse and animal protein
      prevalence over vegetable proteins in patient ration. Atherogenic shift in a
      ration of patients with AH and suffered from HRFS has been exposed more strongly
      in all aged group but mostly evident in patients aged 40 and after. Alcohol
      consumption in men with AH and suffered from HFRS is higher than in healthy
      peers. Interaction between atherogenic unbalance on the main nutrients in
      patients with HFRS and arterial hypertension has been defined. Consumatory
      behavior correction is to be taken to prevent arterial hypertension in recovered
      patients suffered from HFRS.

PMID- 29378099
TI  - [Genetic mice models of type 2 diabetes for evaluation of the effectiveness of
      minor biologically active food substances].
AB  - This report is devoted to discussion of type 2 diabetes experimental modelling on
      genetic mice lines. These laboratory animals, the same as genetic rats lines, are
      usually used in type 2 diabetes experimental modelling. The problem of using mice
      with genetic obesity in modeling of type 2 diabetes is discussed in details in
      the review. In this article the authors shortly characterize the congenic line of
      mice KKAU, suffering from genetic obesity and hyperinsulinemia. The features of
      modelling type 2 diabetes using ob/ob and db/db mice are described closely. The
      phenotype of the animals comes into obesity, infertility, brakes in length
      growth, hyperinsulinemia and dysimmunity. Neither leptin mRNA, nor the hormone
      itself are synthesized in ob/ob mice, leading to ob phenotype formation. Whilst
      db/db mice have two mutant copies of leptin receptor gene, which leads to gradual
      hyperglycemia and obesity progression, followed by hyperinsulemia similar to
      human type 2 diabetes. C57BL/KsLeprdb/+ mice with recessive gene leptin receptoi
      Lepinlb (db) is very perspective genetic type 2 diabetes model developed in
      Russia. TSOD mice are used as an alternative model (Tsumura Suzuki, diabetes with
      obesity), showing diabetes and obesity symptoms with marked hyperinsulinemia and
      pancreatic gland hypertrophy. Thus, presented in this review scientific reports
      approve wide opportunities of effective usage of genetic lines of small
      laboratory animals (mice) for type 2 diabetes modelling.

PMID- 29378100
TI  - [The influence of nettle and burdock extracts in combination with different diets
      on dyslipidemia in diabetes mellitus model].
AB  - The influence of low-fat diet, nettle (Urtica dioica) leafs and burdock (Arctium
      lappa) roots extracts on lipid metabolism and glycosylation reactions has been
      investigated in experimental diabetes mellitus. These extracts were applied in
      diets with both high and low fat content. The experiments were performed on 90
      noninbred male albino rats (200-220 g) that were divided into 9 experimental
      groups. Diabetes mellitus was modeled with twice-repeated intraperitoneal
      streptozotocin (30 mg/kg) injections. The animals received food with increased
      fat content (proteins - 8%, fats - 30%, carbohydrates - 62% of total daily
      caloric content) during 4 weeks before streptozotocine injections and 8 weeks
      after its discontinuation. Simultaneously the rats were daily administered nettle
      leafs (100 mg/kg), burdock roots (25 mg/kg) extracts or metformin (100 mg/kg)
      into the stomach during 10 days. During the period of agents introduction half
      the animals continued to receive food with high fat content, the other half
      received low fat diet (proteins - 20%, fats - 8%, carbohydrates - 72% of the
      total daily caloric content). The forth (control) group received low fat food
      only without extracts or metformin administration. The levels of blood glucose,
      glycosylated hemoglobin, malonic dialdehyde, lipid and lipoprotein fractions
      content were measured. It has been shown that after streptozotocine injections
      and 30% fat diet consumption the blood glucose level increased by 5.3 fold
      compared to that of the intact animals, the content of atherogenic lipid
      fractions increased by 2-8.3 fold and the protein glycosylation reactions were
      intensified by 1.9-2.5 fold. In animals fed with 8% fat diet the blood glucose
      and malonic dialdehyde content decreased by 1.8-2.3 fold. In this experiment the
      levels of triglycerides, total cholesterol, cholesterol of nonhigh-density
      lipoproteins, low-density and very low-density lipoproteins, as well as the
      cholesterol and protein content of high-density lipoproteins normalized. The low
      fat food did not cause glycosylation reactions regression. With the
      administration of nettle, burdock extracts or metformin to animals that continued
      to receive high fat food the blood glucose, triglycerides, total cholesterol,
      cholesterol of nonhigh-density lipoproteins, low-density and very low-density
      lipoproteins levels decreased by l.6-7.l fold as compared to the parameters in
      streptozotocine diabetes mellitus. Cholesterol and protein content of high
      density lipoproteins increased by l.4-3.7 fold. The herbal extracts also
      prevented malonic dialdehyde formation, high-density lipoproteins and hemoglobin
      glycosylation. The nettle and burdock extracts more effectively decreased
      hyperglycemia, hypertriglyceridemia and lipoperoxidation in animals fed with low
      fat food. Metformin in the experiment with low fat intake decreased the glucose,
      low-density and very low-density lipoproteins content to a maximal degree and
      prevented high-density lipoproteins glycosylation.

PMID- 29378101
TI  - [Effects of omega-3 polyunsaturated fatty acids on the state of insulin
      resistance, the content of some pro- and antiinflammatory factors in patients
      with type 2 diabetes mellitus and cardiovascular autonomic neuropathy].
AB  - We have investigated the influence of the long-chain omega-3 polyunsaturated
      fatty acids (omega-3 PUFA) administration on the insulin resistance parameters,
      levels of high sensitivity C-reactive protein (hsCRP), some pro- and anti
      inflammatory cytokines in patients with type 2 diabetes mellitus (T2 DM) and
      cardiovascular autonomic neuropathy (CAN). The study involved 12 patients with T2
      DM without verified cardiovascular diseases (CVD), 36 patients with T2 DM and
      functional stage of CAN, of median age 50-59 years, disease duration 1-6 years
      and HbA1c levels - 7.1+/-0.6%. 15 healthy subjects were control group. Screening
      for CAN, that included five standard cardiovascular tests, was performed.The
      levels of blood glucose, HbA1c, immunoreactive insulin (IRI), hsCRP, tumor
      necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-8 and IL-10 were
      measured. The index of insulin resistance (HOMA-IR) and TNFalpha/IL-10 ratio were
      calculated. Patients with T2 DM and CAN were divided into 2 groups: patients of
      the 1st group (group of comparison, n=15) received standard glucose-lowering
      therapy; patients of the 2nd group (n=21) received one capsule/day of the omega-3
      PUFA (~90% ethyl ester of PUFA (1000 mg), in particular eicosapentaenoic - 460
      mg, docosahexaenoic acid - 380 mg and 4 mg alpha-tocopherol acetate) in addition
      to the standard therapy. The duration of the study was 3 months. Obtained results
      showed, that development of CAN in patients with T2 DM is accompanied by increase
      of the IRI (26.6+/-1.73 mcIU/ml, p<0.001 - compared to the control; p1<0.001 -
      compared to T2 DM patients without CVD); hsCRP (2.77+/-0.24 mg/l, p<0.001,
      p1<0,001); TNFalpha (5.75+/-0.24 pg/ml, p<0.001, p1<0.001); IL-6 (5.88+/-0.38
      pg/ml, p<0.001, p1<0.001); IL-8 (6.65+/-0.3 pg/ml, p<0.001, p1>0.05); IL-10
      (15.86+/-1.4 pg/ml, p<0.05, p1>0.05) levels; TNFalpha/IL-10 (44.2+/-3.57%,
      p<0.01, p1<0.05) and HOMA-IR. After 3 months of treatment no statistically
      significant changes (p>0.05) of investigated parameters, in particular levels of
      IRI (-6.8+/-2.0%); hsCRP (-7.2+/-1.63%); TNFalpha (-6.1+/-1.0%); IL-6 (-5.8+/
      1.77%); IL-8 (-3.9+/-1.57%); IL-10 (-3.7+/-2.34%); TNFalpha/IL-10 (-0.5+/-2.3%)
      in patients from the group of comparison were found. The administration of omega
      3 PUFA to patients with T2 DM and CAN promoted to the statistically significant
      decrease in hsCRP (-14.8+/-2.91%, p<0.05), TNFalpha (-14.1+/-2.15%, p<0.01), IL-6
      (-13.5+/-2.7%, p<0.05), IL-8 (-9.8+/-2.13%, p<0.05), TNFalpha/IL-10 ratio (
      34.6+/-1.93%, p<0.05); a slighty decrease in the content of the IRI (-10.3+/
      1.1%, p>0.05), IL-10 (+7.9 +/-6.42%, p>0.05), HOMA-IR was observed. Obtained
      results could witness, that prescription of omega-3 PUFA leads to decrease of the
      proinflammatory immune response activity and allows to consider omega-3 PUFA as a
      promising medicine in treatment and/or prevention of CAN in patients with DM 2.

PMID- 29378102
TI  - [Dry jelly concentrate with vitamins and dietary fiber in patients with IBS with
      constipation: a comparative controlled study].
AB  - Irritable bowel syndrome (IBS) is highly prevalent functional gastrointestinal
      disorder associated with decrease in quality of life and a high social cost. Diet
      is one of several therapeutic options in IBS treatment; therefore the development
      and clinical evaluation of innovative functional food for IBS patients is useful.
      Dry jelly concentrate containing 3 g inulin, 10 mg curcumin and 1.8 mg of
      pyridoxine was developed and clinically evaluated. Fifty patients fulfilling the
      Rome III criteria for IBS-C were randomly assigned into two groups: one received
      standard diet plus two jelly drinks a day for 2 weeks and control group received
      standard diet. Response to therapy was recorded on a daily basis using Likert
      scale of abdominal pain, bloating and feeling of incomplete bowel emptying,
      frequency of bowel movement, Bristol stool scale, and quality of life assessed by
      IBSQoL questionnaire before and after the treatment. Intake of functional food
      product (jelly) containing inulin and curcumin is associated with a significant
      positive effect on the stool parameters (from 0.6+/-0.24 to 1.15+/-0.65 t/d in
      stool frequency, p=0.001, from 2.62+/-1.23 to 3.99+/-1.27, index Bristol scale,
      p=0.001), a reduce of the severity of abdominal pain (from 1.69+/-0.71 to 1.36+/
      0.44 Likert scale points, p=0.001), bloating (from 2.03+/-0.89 to 1.55+/-0.81
      points of Likert scale, p=0.02) and a sense of incomplete bowel emptying (from
      2.25+/-0.98 to 1.68+/-0.92 points of Likert scale, p=0.001), as well as an
      increase in quality of life (from 64.5+/-13.5 to 81.2+/-9.1%, r=0.05). Patients
      in control group have improvement in abdominal pain (from 2.16+/-0.58 to 1.8+/
      0.61 Likert scale points, p=0.05) and bloating (from 2.42+/-0.83 to 2.16+/-0.71
      Likert scale points, p=0.05) only. During the treatment period no significant
      adverse events were found. These results indicate that jelly concentrate
      containing inulin, curcumin and pyridoxine improves abdominal pain score, Bristol
      scale index and quality of life in patients with IBS-C.

PMID- 29378103
TI  - [Influence of cookies with a modified carbohydrate profile on postprandial
      glycemia in patients with type 2 diabetes].
AB  - The aim of the study was assessment of influence of cookies with a modified
      carbohydrate profile on postprandial glycemia in patients with type 2 diabetes.
      The study included 20 patients 35-69 years old, with type 2 diabetes and obesity
      II-III degrees (BMI=40.2+/-1.1 kg/m2) treated with standard hypoglycemic therapy.
      At the time of the initial evaluation all patients were determined at the stage
      of metabolic subcompensation: glucose basal level in venous blood was 6.8+/-0.3
      mmol/l; in capillary blood - 6.5+/-0.5 mmol/l; the level of glycated hemoglobin -
      7.2+/-0.2%. Glucose blood plasma level on an empty stomach and within 3 hours
      after the consumption of biscuits with modified carbohydrate profile (25 g
      digestible carbohydrates) and wheat bread containing 25 g digestible
      carbohydrates (control) was determined. Calculation of the area under the
      glycemic curve was conducted by standard technique. Portability of cookies with a
      modified carbohydrate profile (replacement of wheat flour to the mixture of
      buckwheat, oat and barley flour and the use of maltitol) was good, with no side
      effects or signs of intolerance were observed. It has been shown that consumption
      of biscuits with a modified carbohydrate profile was accompanied by a
      significantly smaller rise in blood glucose level after 30 min from the start of
      the study, compared with the standard food load (an average of 19.1% and 42.4%,
      respectively, from baseline, p<0.05). After 120 and 180 min after the test food
      loads glycemia changed equally, without significant differences between
      foodstuffs. Area under the glycemic curve in the consumption of cookies with a
      modified carbohydrate profile was significantly less than under the standard food
      load (184.6+/-16.7 vs. 236.9+/-21.2 mmol/l*min, p<0.05). Consumption of biscuits
      with modified carbohydrate profile was accompanied by less severe postprandial
      glycemic response in patients with type 2 diabetes in comparison with that at a
      standard load food containing 25 g digestible carbohydrates.

PMID- 29378105
TI  - [The role of the food industry in dietetic therapy of the population. Specialized
      confectionery diabetic food].
AB  - Diabetes mellitus is a serious health and social problem of modernity, which in
      the future will increase and experts predict that the number of patients in 2030
      will exceed 438,4 million. Taking into account the seriousness of the problem,
      and the fact that diabetes hurts an increasing number of young adults, the
      problem of creating diabetic food products, the positive effect of which on the
      organism is confirmed by experimental and clinical studies, is very relevant. The
      overview briefly covers information about the role of diet and ways to modify the
      composition and formulations of confectionery products of industrial production.
      The results of industry work towards the development of diabetic confectionery
      products in Russian Federation and peculiarities of their production and
      implementation in the framework of the Customs Union countries are summarized.
      Monitoring of the information entered in the register of specialized food
      products has been carried out, the lack of common approaches and tools in
      regulation imposed on the diabetic products in Russia, Belarus and Kazakhstan has
      been revealed. The necessity of objective regulatory impact assessment has been
      established. Its results will form the basis of the development of a unified
      approach to the production, handling and identification of diabetic confectionery
      and of the introduction of the General principle in relation to the probative
      value of the data, confirming their quality and safety. To improve the quality of
      population life and to reduce losses from socially significant diseases is
      possible through the development of personalized diets and their filling with
      products with attractive sensory properties. These data indicate the need for
      training highly qualified specialists with interdisciplinary knowledge in the
      field of food technology, nutrition and medicine.

PMID- 29378104
TI  - [Comparative assessment of efficiency of the low-calorie diets modified by
      proteinaceous and vitamin cocktails].
AB  - The aim of the work is comparative assessment of efficiency of a hypocaloric diet
      with inclusion of proteinaceous and vitamin cocktails at obesity. 90 patients
      with obesity of the II-III degree at the age of 18-65 years by the principle of
      casual selection were divided into three groups. Control group (30 patients)
      received a standard low-calorie diet with an energy value of 1600 kcal/day. The
      diet of the 1st group (30 patients) was modified by the inclusion of protein
      vitamin-mineral cocktail (16 g of dry mixture with the addition of 250 ml of
      yogurt 1.0% fat) twice a day, diet of the 2nd group (30 patients) - the inclusion
      of a protein cocktail (16 g of dry mixture with the addition of 250 ml of yogurt
      1.0% fat), while excluding from the diet equivalent caloric meals. The 1st group
      of patients had a decrease in fat mass by 4.2+/-0.7 kg (p<0.02), in active lean
      mass by 1.1+/-0.1 kg, in total fluid volume by 2.2+/-0.3 kg (p<0.02). The 2nd
      group of patients had a decrease in fat mass by 3.8+/-0.9 kg (p<0.01), in lean
      mass by 1.4+/-0.3 kg and in the total fluid volume by 3.1+/-0.9 l (p<0.02). In
      the control group attention should be paid to a decrease in lean mass by 1.9+/
      0.6 kg, while fat mass decreased by 3.0+/-0.4 kg (p<0.02) and the total fluid
      volume by 3.1+/-0.9 l (p<0.02). Evaluation of the changes of serum biochemical
      parameters after treatment demonstrated that the 1st group of patients had
      significant favorable dynamics of reduction of serum level of total cholesterol,
      uric acid and glucose (17.7, 28.2 and 18.3%, respectively), which was more
      pronounced compared with the dynamics in the control group (the decrease by 15,
      19.2 and 8.2%, respectively). In the 2nd group of patients the decrease rate of
      the observed parameters was less pronounced (15, 19.2 and 8.2%,
      respectively).More appreciable favorable dynamics of biochemical parameters and
      reduction in body weight in the 1st and 2nd groups in relation to the control
      group allow to reasonably apply the protein-vitamin cocktails in a diet therapy
      at obesity.

PMID- 29378106
TI  - [Group preventive consultation of the population concerning nutrition. Experience
      of School of the balanced nutrition founded on the basis of the Health center].
AB  - The development of the program of group preventive consultation of visitors of
      the centers of health concerning nutrition and assessment of its efficiency was
      the purpose of the work. The analysis of the results of inspection of 2569
      visitors of the Health senter at the age of 18-78 years and randomized, open,
      cross research of 242 women (27-72 years old) who passed group preventive
      consultation in the Center of health at "School of a balanced nutrition " were
      carried out. Anthropometrical data and the actual nutrition with use of the
      computer program "Analysis of the Person Nutrition" were studied. The study of
      nutritional status of 242 women with different body mass revealed an excess
      consumption of fats and carbohydrates, dietary energy supply in obese.Basing on
      the structural features of patient's nutrition the School nutrition program was
      developed. Somparing of laboratory, diagnostic and resource capabilities of
      Health senter with algorithm of overweight and obesity patients treatment has
      shown wide opportunities of Health senter, not only in the diagnosis (the study
      of nutrient, metabolic status), but also in the complex treatment of patients
      with different body mass. Due to group preventive counseling in the School of a
      balanced nutrition the efficiency of such an approach contributed 1-month weight
      loss (2.18+/-1.28 kg) in 64.4% of the participants.

PMID- 29378107
TI  - [Theoretical and practical aspects of development of biscuits with a modified
      carbohydrate profile for patients with type 2 diabetes].
AB  - The purpose of this research was to develop formulation and technology of flour
      confectionery products in the form of biscuits with a modified carbohydrate
      profile, a study of physico-chemical and structural-mechanical properties. The
      objects of this research were: basic food matrix, are the prototype of the
      designed product without modification of the carbohydrate profile prepared by the
      classic recipe and traditional technologies; model samples of cookies with a
      modified carbohydrate profile; the experimental sample cookie with a modified
      carbohydrate profile and optimized physic-chemical, structural-mechanical and
      organoleptic indicators. Determination of physic-chemical and organoleptic
      characteristics of biscuits was carried out by standard methods. The water
      activity was determined on the analyzer using a cooled mirror dew point sensor,
      structural-mechanical properties - on texturename with conical and cylindrical
      nozzles, imitating the processes of breakage and bite, describing the hardness,
      brittleness, breakage, and other properties of a food product. The modification
      of the carbohydrate profile of biscuit, consisting in the replacement of wheat
      flour traditionally used in the recipe of flour confectionery products, by the
      composition containing oat, barley and buckwheat flour, and in the exclusion of
      sugar and the introduction of ingredients that do not cause hyperglycemic effect:
      maltitol as a sweetener and beta-glucans. The technological scheme of production
      of new kinds of cookies has been developed, the parameters of the production
      process have been worked out, physical-chemical, structural-mechanical and
      organoleptic properties of a new type of cookie have been optimized. Analysis of
      the chemical composition of the cookies showed that 100 g contains 9.3 g of
      protein, 17.0 g of fat and 44.5 g of carbohydrates, including 42.4 g of starch,
      and 2.1 g mono- and disaccharides, 2.2 g dietary fiber, 20 g maltitol; caloric
      value of 420 kcal/1760 kJ. In accordance with the developed technology an
      experimental batch of cookies with a modified carbohydrate profile has been
      produced to evaluate its impact on postprandial glycemia in patients with type 2
      diabetes.

PMID- 29378108
TI  - [Nutrition value of national milk products with the addition of wild berries and
      wild food plants of Yakutia].
AB  - Results of an assessment of the actual food of the population in various
      medicoeconomic zones of the republic (industrial, agricultural, Arctic) by method
      of the frequency analysis of food consumption are presented in the article. The
      analysis of control of compliance of quality and safety of foodstuff in the
      Republic of Sakha (Yakutia), according to requirements of the legislation of the
      Russian Federation, acts of the Customs union has been made. Decreased
      consumption of such foodstuff as milk, fish and meat products including products
      from local food staples and national dishes has been established. The data
      obtained are medic-biological justification for search of ways of optimization of
      population nutrition, creation of specialized products with a functional purpose
      and for the prevention of the states and diseases connected with nutrition
      violation. They also define innovative development of the republic in questions
      of biotechnologies of the production of specialized foods for various groups of
      the population. Results of chemical composition research of the most used wild
      growing food plants of Yakutia are given. The questions connected with the
      nutrition and biological value of the dairy products of a functional purpose with
      use of wild-growing food herbs and berries of Yakutia are discussed.

PMID- 29378109
TI  - [Vitamin-mineral supplements in nutrition of adults].
AB  - The diet of population consisting of natural products is quite adequate and even
      excessive of energy consumption, but is not able to meet fully the need of
      organism in a number of micronutrients. Due to lack of sun exposure and long
      presence indoors endogenous synthesis of vitamin D in the skin by ultraviolet
      radiation does not provide the body's need for this vitamin. Intake of
      vitaminmineral supplements (VMS) is appropriate because combined deficiency of
      vitamins and minerals takes place in population. Prophylactic doses (equal to
      physiological needs) provide a diet completeness and reduce the risk of vitamin
      deficiency and its consequences. The high incidence of combined deficiency of
      vitamins among population and the existence of vitamin interactions are the basis
      for the application of the multivitamins. The simultaneous intake of vitamins is
      more physiological, their combination is more effective than a separate or
      isolated destination of each of them. Efficacy of the VMS has been shown in the
      treatment and prevention of some diseases. The main requirements for the VMS are
      full list of vitamins and minerals, the lack of which is detected most
      frequently, in doses covering the needs of organism. For the health of the
      pregnant woman and her unborn child preference should be given for complexes,
      containing DHA and/or probiotics along with vitamins. The principles of the
      selection of the composition and vitamin doses in the VMS for using patients
      suffering from various pathologies should be based on data on the patient's
      sufficiency with vitamins, the understanding of the role of vitamin deficiency in
      the pathogenesis of the disease, as well as on the composition of the diet and
      its modifications.

PMID- 29378110
TI  - Measuring Dipole Inversion in Self-Assembled Nano-Dielectric Molecular Layers.
AB  - A self-assembled nanodielectric (SAND) is an ultrathin film, typically with
      periodic layer pairs of high-k oxide and phosphonic-acid-based pi-electron (PAE)
      molecular layers. IPAE, having a molecular structure similar to that of PAE but
      with an inverted dipole direction, has recently been developed for use in thin
      film transistors. Here we report that replacing PAE with IPAE in SAND-based thin
      film transistors induces sizable threshold and turn-on voltage shifts, indicating
      the flipping of the built-in SAND polarity. The bromide counteranion (Br-)
      associated with the cationic stilbazolium portion of PAE or IPAE is of great
      importance, because its relative position strongly affects the electric dipole
      moment of the organic layer. Hence, a set of X-ray synchrotron measurements were
      designed and performed to directly measure and compare the Br- distributions
      within the PAE and IPAE SANDs. Two trilayer SANDs, consisting of a PAE or IPAE
      layer sandwiched between an HfOx and a ZrOx layer, were deposited on the SiOx
      surface of Si substrates or periodic Si/Mo multilayer substrates for X-ray
      reflectivity and X-ray standing wave measurements, respectively. Along with
      complementary DFT simulations, the spacings, elemental (Hf, Br, and Zr)
      distributions, molecular orientations, and Mulliken charge distributions of the
      PAE and IPAE molecules within each of the SAND trilayers were determined and
      correlated with the dipole inversion.

PMID- 29378111
TI  - Ion-Exchanged SAPO-34 Membranes for Krypton-Xenon Separation: Control of
      Permeation Properties and Fabrication of Hollow Fiber Membranes.
AB  - Separation of radioisotope 85Kr from 136Xe is of importance in used nuclear fuel
      reprocessing. Membrane separation based on zeolite molecular sieves such as
      chabazite SAPO-34 is an attractive alternative to energy-intensive cryogenic
      distillation. We report the synthesis of SAPO-34 membranes with considerably
      enhanced performance via thickness reduction based upon control of a steam
      assisted vapor-solid conversion technique followed by ion exchange with alkali
      metal cations. The reduction of membrane thickness leads to a large increase in
      Kr permeance from 7.5 to 26.3 gas permeation units (GPU) with ideal Kr/Xe
      selectivities >20 at 298 K. Cation-exchanged membranes show large (>50%)
      increases in selectivity at ambient or slight subambient conditions. The
      adsorption, diffusion, and permeation characteristics of ion-exchanged SAPO-34
      materials and membranes are investigated in detail, with potassium-exchanged SAPO
      34 membranes showing particularly attractive performance. We then demonstrate the
      fabrication of selective SAPO-34 membranes on alpha-alumina hollow fibers.

PMID- 29378112
TI  - Scopolamine-Induced Memory Impairment Is Alleviated by Xanthotoxin: Role of
      Acetylcholinesterase and Oxidative Stress Processes.
AB  - Xanthotoxin, popularly occurring furanocoumarin, which can be found in plants
      from the Apiaceae family, was isolated from fruits of Pastinaca sativa L. by mean
      of high-performance countercurrent chromatography, and its effects on the
      scopolamine-induced cognitive deficits in male Swiss mice using the passive
      avoidance (PA) test were evaluated. To measure the acquisition of memory
      processes, xanthotoxin (1, 2.5, 5 mg/kg) was administered 30 min before PA test
      and scopolamine was administered 10 min after xanthotoxin. To measure the
      consolidation of memory processes, xanthotoxin (1 and 2.5 mg/kg) was injected
      immediately after removing the mouse from the apparatus and 10 min after
      scopolamine was administered. In subchronic experiments, mice were injected with
      xanthotoxin (1 mg/kg) or saline, 6 days, twice daily. At 24 h after the last
      injection of the drugs, the hippocampus and the prefrontal cortex were removed
      for biochemical assays. The results demonstrated that either single (2.5 and 5
      mg/kg) or repeatable (1 mg/kg) administration of xanthotoxin significantly
      increased index of latency (IL) in both acquisition and consolidation of memory
      processes, showing some procognitive effects. The behavioral tests also showed
      that an acute (2.5 mg/kg) and subchronic (1 mg/kg) administration of xanthotoxin
      prevent memory impairment induced by injection of scopolamine (1 mg/kg). Observed
      effects could be due to the inhibition of acetylcholinesterase activities and
      amelioration of oxidative stress processes in the hippocampus and the prefrontal
      cortex. It was suggested that xanthotoxin could show neuroprotective effect in
      scopolamine-induced cognitive impairment connected to cholinergic
      neurotransmission and oxidative stress in the brain structures.

PMID- 29378113
TI  - Unified Theory of Vapor-Wall Mass Transport in Teflon-Walled Environmental
      Chambers.
AB  - Secondary organic aerosol (SOA) formation is studied in laboratory chambers, in
      which volatile organic compounds (VOCs) are oxidized to produce low-volatility
      compounds that condense into the aerosol phase. It has been established that such
      oxidized low-volatility compounds can partition into the chamber walls, which
      traditionally consist of Teflon film. Several studies exist in which the rates of
      uptake of individual vapor compounds to the chamber walls have been measured, but
      a unified theory capable of describing the range of experimental measurements has
      been lacking. Here, a two-layer model of observed short and long vapor-wall
      interaction time scales in Teflon-walled environmental chambers is presented and
      shown to be consistent with experimental data on the rate of wall deposition of
      more than 90 compounds. Semiempirical relationships between key parameters in the
      model and vapor molecular properties are derived, which can be used to predict
      the fate of gas-phase vapor in the chamber under dry conditions.

PMID- 29378115
TI  - Pd-Catalyzed Acetoxylation of gamma-C(sp3)-H Bonds of Amines Directed by a
      Removable Bts-Protecting Group.
AB  - Pd-catalyzed acetoxylation of gamma-C(sp3)-H bonds directed by Bts-protected
      amines using inexpensive PhI(OAc)2 as oxidant is reported. The Bts-protecting
      group is easily introduced and removed under mild conditions. This protocol
      provides an important strategy for the construction of gamma-hydroxyl amine
      derivatives.

PMID- 29378116
TI  - Islet Amyloid Polypeptide Promotes Amyloid-Beta Aggregation by Binding-Induced
      Helix-Unfolding of the Amyloidogenic Core.
AB  - Amyloid aggregation of amyloid-beta (Abeta) and islet amyloid polypeptide (IAPP)
      is associated with Alzheimer's disease (AD) and type-2 diabetes (T2D),
      respectively. With T2D being the risk factor for AD and the ability of IAPP to
      cross the blood-brain barrier, the coaggregation of Abeta and IAPP has been
      explored to understand the cross-talk between the two diseases. Recent studies
      demonstrated that soluble IAPP could significantly accelerate the aggregation of
      Abeta while preformed amyloids of IAPP were poor "seeds" for Abeta aggregation.
      Here, we apply all-atom discrete molecular dynamics simulations to investigate
      possible molecular mechanisms for the accelerated coaggregation of IAPP and
      Abeta42 comparing to Abeta42 aggregation alone, which was confirmed by the
      complementary thioflavin-T fluorescence assay. Our simulation results suggest
      that peptides in the mixture tend to form heterodimers as the first step toward
      their coaggregation. Strong interpeptide interactions with IAPP in the
      heterodimer shift the helical conformation of Abeta42 in its amyloidogenic
      central hydrophobic core, residues 16-22 (Abeta16-22), to the extended
      conformation ready to form beta-sheets. Our study suggests that the unfolding of
      Abeta16-22 helix contributes to the aggregation free-energy barrier and
      corresponds to the rate-limiting conformational change for Abeta42 aggregation.
      Therefore, we propose that soluble IAPP promotes the aggregation of Abeta42 by
      binding-induced conformational change of Abeta42 in its amyloidogenic core and
      thus reduced aggregation free-energy barrier.

PMID- 29378117
TI  - Enhancement of Curcumin Bioavailability by Encapsulation in Sophorolipid-Coated
      Nanoparticles: An in Vitro and in Vivo Study.
AB  - There is great interest in developing colloidal delivery systems to enhance the
      water solubility and oral bioavailability of curcumin, which is a hydrophobic
      nutraceutical claimed to have several health benefits. In this study, a natural
      emulsifier was used to form sophorolipid-coated curcumin nanoparticles. The
      curcumin was loaded into sophorolipid micelles using a pH-driven mechanism based
      on the decrease in curcumin solubility at lower pH values. The sophorolipid
      coated curcumin nanoparticles formed using this mechanism were relatively small
      (61 nm) and negatively charged (-41 mV). The nanoparticles also had a relatively
      high encapsulation efficiency (82%) and loading capacity (14%) for curcumin,
      which was present in an amorphous state. Both in vitro and in vivo studies showed
      that the curcumin nanoparticles had an appreciably higher bioavailability than
      that of free curcumin crystals (2.7-3.6-fold), which was mainly attributed to
      their higher bioaccessibility. These results may facilitate the development of
      natural colloidal systems that enhance the oral bioavailability and bioactivity
      of curcumin in food, dietary supplements, and pharmaceutical products.

PMID- 29378114
TI  - Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy.
AB  - The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) has received significant attention as a cancer therapeutic due to its
      ability to selectively trigger cancer cell apoptosis without causing toxicity in
      vivo. While TRAIL has demonstrated significant promise in preclinical studies in
      mice as a cancer therapeutic, challenges including poor circulation half-life,
      inefficient delivery to target sites, and TRAIL resistance have hindered clinical
      translation. Recent advances in drug delivery, materials science, and
      nanotechnology are now being exploited to develop next-generation nanoparticle
      platforms to overcome barriers to TRAIL therapeutic delivery. Here, we review the
      design and implementation of nanoparticles to enhance TRAIL-based cancer therapy.
      The platforms we discuss are diverse in their approaches to the delivery problem
      and provide valuable insight into guiding the design of future nanoparticle-based
      TRAIL cancer therapeutics to potentially enable future translation into the
      clinic.

PMID- 29378118
TI  - Role of Nitrogen Dioxide in the Production of Sulfate during Chinese Haze-Aerosol
      Episodes.
AB  - Haze events in China megacities involve the rapid oxidation of SO2 to sulfate
      aerosol. Given the weak photochemistry that takes place in these optically thick
      hazes, it has been hypothesized that SO2 is mostly oxidized by NO2 emissions in
      the bulk of pH > 5.5 aerosols. Because NO2(g) dissolution in water is very slow
      and aerosols are more acidic, we decided to test such a hypothesis. Herein, we
      report that > 95% of NO2(g) disproportionates [2NO2(g) + H2O(l) = H+ + NO3-(aq) +
      HONO (R1)] upon hitting the surface of NaHSO3 aqueous microjets for < 50 MUs,
      thereby giving rise to strong NO3- ( m/ z 62) signals detected by online
      electrospray mass spectrometry, rather than oxidizing HSO3- ( m/ z 81) to HSO4- (
      m/ z 97) in the relevant pH 3-6 range. Because NO2(g) will be consumed via R1 on
      the surface of typical aerosols, the oxidation of S(IV) may in fact be driven by
      the HONO/NO2- generated therein. S(IV) heterogeneous oxidation rates are expected
      to primarily depend on the surface density and liquid water content of the
      aerosol, which are enhanced by fine aerosol and high humidity. Whether aerosol
      acidity affects the oxidation of S(IV) by HONO/NO2- remains to be elucidated.

PMID- 29378119
TI  - High-Performance Carbon Nanotube Complementary Electronics and Integrated Sensor
      Systems on Ultrathin Plastic Foil.
AB  - The longtime vacancy of high-performance complementary metal-oxide-semiconductor
      (CMOS) technology on plastics is a non-negligible obstacle to the applications of
      flexible electronics with advanced functions, such as continuous health
      monitoring with in situ signal processing and wireless communication
      capabilities, in which high speed, low power consumption, and complex
      functionality are desired for integrated circuits (ICs). Here, we report the
      implementation of carbon nanotube (CNT)-based high-performance CMOS technology
      and its application for signal processing in an integrated sensor system for
      human body monitoring on ultrathin plastic foil with a thickness of 2.5 MUm. The
      performances of both the p- and n-type CNT field-effect transistors (FETs) are
      excellent and symmetric on plastic foil with a low operation voltage of 2 V:
      width-normalized transconductances ( gm/ W) as high as 4.69 MUS/MUm and 5.45
      MUS/MUm, width-normalized on-state currents reaching 5.85 MUA/MUm and 6.05
      MUA/MUm, and mobilities up to 80.26 cm2.V-1.s-1 and 97.09 cm2.V-1.s-1,
      respectively, together with a current on/off ratio of approximately 105. The
      devices were mechanically robust, withstanding a curvature radius down to 124
      MUm. Utilizing these transistors, various high-performance CMOS digital ICs with
      rail-to-rail output and a ring oscillator on plastics with an oscillation
      frequency of 5 MHz were demonstrated. Furthermore, an ultrathin skin-mounted
      humidity sensor system with in situ frequency modulation signal processing
      capability was realized to monitor human body sweating.

PMID- 29378120
TI  - Betulin-Constituted Multiblock Amphiphiles for Broad-Spectrum Protein Resistance.
AB  - Multiblock-like amphiphilic polyurethanes constituted by poly(ethylene oxide) and
      biosourced betulin are designed for antifouling and synthesized by a convenient
      organocatalytic route comprising tandem chain-growth and step-growth
      polymerizations. The doping density of betulin (DB) in the polymer chain
      structure is readily varied by a mixed-initiator strategy. The spin-coated
      polymer films exhibit unique nanophase separation and protein resistance
      behaviors. Higher DB leads to enhanced surface hydrophobicity and, unexpectedly,
      improved protein resistance. It is found that the surface holds molecular-level
      heterogeneity when DB is substantially high due to restricted phase separation;
      therefore, broad-spectrum protein resistance is achieved despite considerable
      surface hydrophobicity. As DB decreases, the distance between adjacent betulin
      units increases so that hydrophobic nanodomains are formed, which provide enough
      landing areas for relatively small-sized proteins to adsorb on the surface.

PMID- 29378122
TI  - A Definition of the Magnetic Transition Temperature Using Valence Bond Theory.
AB  - Macroscopic magnetic properties are analyzed using Valence Bond theory. Commonly
      the critical temperature TC for magnetic systems is associated with a maximum in
      the energy-based heat capacity Cp(T). Here a more broadly applicable definition
      of the magnetic transition temperature TC is described using the spin moment
      expectation value (i.e., applying the spin exchange density operator) instead of
      energy. Namely, the magnetic capacity Cs(T) reflects variation in the spin
      multiplicity as a function of temperature, which is shown to be related to
      ?[chiT(T)]/?T. Magnetic capacity Cs(T) depends on long-range spin interactions
      that are not relevant in the energy-based heat capacity Cp(T). Differences
      between Cs(T) and Cp(T) are shown to be due to spin order/disorder within the
      crystal that can be monitored via a Valence Bond analysis of the corresponding
      magnetic wave function. Indeed the concept of the Boltzmann spin-alignment order
      is used to provide information about the spin correlation between magnetic units.
      As a final illustration, the critical temperature is derived from the magnetic
      capacity for several molecular magnets presenting different magnetic topologies
      that have been experimentally studied. A systematic shift between the transition
      temperatures associated with Cs(T) and Cp(T) is observed. It is demonstrated that
      this shift can be attributed to the loss of long-range spin correlation. This
      suggests that the magnetic capacity Cs(T) can be used as a predictive tool for
      the magnetic topology and thus for the synthetic chemists.

PMID- 29378121
TI  - Lyophilic but Nonwettable Organosilane-Polymerized Carbon Dots Inverse Opals with
      Closed-Cell Structure.
AB  - This paper presents a unique lyophilic but nonwettable property of organosilane
      polymerized carbon dots inverse opals photonic crystals (SiCDPCs) with closed
      cell structure. Little stopband shift was observed for the SiCDPCs when being
      immersed into the solvents such as isopropanol, olive oil, DMSO, hexane, silicone
      oil, ethanediol, etc. but keeping lyophilic property. This could be attributed to
      the combined effect of closed-cell structure and the unique chemical composition
      of SiCDPCs. Furthermore, more than 30 kinds of organic solvents had been
      investigated, it was found that there were two kinds of factors that affected the
      stopband shift upon solvent's immersing; one was the polarity of solvent, and the
      other one was the viscosity of solvent. That is, mainly nonpolar or high
      viscosity solvents showed lyophilic but nonwettable property. The distinct
      solvent-responsive behaviors of the SiCDPCs toward polar/nonpolar solvents had
      been utilized for the fabrication of 2D/3D pattern. Additionally, the as-prepared
      SiCDPCs showed improved optical limiting property, excellent low-temperature
      resistance, and abrasion tolerant property. It is of great importance for the
      development of multifunctional novel coating materials and creation of novel
      optical devices.

PMID- 29378123
TI  - Tuning the Strength of the Resonance-Assisted Hydrogen Bond in o
      Hydroxybenzaldehyde by Substitution in the Aromatic Ring1.
AB  - Intramolecular resonance-assisted hydrogen bonds (RAHBs) are stronger than
      conventional hydrogen bonds (HBs) thanks to the extra stabilization connected
      with the partial delocalization of the pi-electrons within the HB motif
      containing conjugated formally single and double bonds. When these conjugated
      bonds are part of an aromatic ring, there is an interplay between resonance
      assisted hydrogen bonding and the aromaticity of the ring. The main aim of the
      present work is to analyze the changes in RAHB strength by substitution in the
      aromatic ring. For this purpose, we use density functional theory methods to
      study all possible mono- and disubstitutions in the four free positions of the
      aromatic ring of o-hydroxybenzaldehyde. As substituents, we consider three pi
      electron donating groups (EDG: NH2, OH, and F) and three pi-electron withdrawing
      groups (EWG: NO2, NO, and CN). We show that it is possible to tune the HB bond
      distance in the RAHB by locating different substituents in given positions of the
      aromatic ring. Indeed, certain combinations of EDG and EWD result in a reduction
      or increase of the HB distance by up to 0.05 A. Results found can be explained by
      considering the existence of a resonance effect of the pi-electrons within the HB
      motif.

PMID- 29378124
TI  - Water Lone Pair Delocalization in Classical and Quantum Descriptions of the
      Hydration of Model Ions.
AB  - Understanding the nature of ionic hydration at a fundamental level has eluded
      scientists despite intense interest for nearly a century. In particular, the
      microscopic origins of the asymmetry of ion solvation thermodynamics with respect
      to the sign of the ionic charge remains a mystery. Here, we determine the
      response of accurate quantum mechanical water models to strong nanoscale
      solvation forces arising from excluded volumes and ionic electrostatic fields.
      This is compared to the predictions of two important limiting classes of
      classical models of water with fixed point changes, differing in their treatment
      of "lone pair" electrons. Using the quantum water model as our standard of
      accuracy, we find that a single fixed classical treatment of lone pair electrons
      cannot accurately describe solvation of both apolar and cationic solutes,
      emphasizing the need for a more flexible description of local electronic effects
      in solvation processes. However, we explicitly show that all water models studied
      respond to weak long-ranged electrostatic perturbations in a manner that follows
      macroscopic dielectric continuum models, as would be expected. We emphasize the
      importance of these findings in the context of realistic ion models, using
      density functional theory and empirical models, and discuss the implications of
      our results for quantitatively accurate reduced descriptions of solvation in
      dielectric media.

PMID- 29378125
TI  - Antitumor Potential of S-Nitrosothiol-Containing Polymeric Nanoparticles against
      Melanoma.
AB  - Melanoma is a malignant proliferative disease originated from melanocyte
      transformations, which are characterized by a high metastatic rate and mortality.
      Advances in Nanotechnology have provided useful new approaches and tools for
      antitumor chemotherapy. The aim of this study was to investigate the molecular
      mechanisms underlying chitosan nanoparticles containing S-nitrosomercaptosuccinic
      acid ( S-nitroso-MSA-CS) induced cytotoxicity in melanoma cells. S-Nitroso-MSA-CS
      induced concentration-dependent cell death against B16-F10 tumor cells, whereas
      non-nitroso nanoparticles (CS or MSA-CS) did not induce significant cytotoxicity.
      Additionally, melanoma cells were more sensitive to cell death than normal
      melanocytes. S-Nitroso-MSA-CS-induced cytotoxicity exhibited features of caspase
      dependent apoptosis, and it was associated with oxidative stress, characterized
      by increased mitochondrial superoxide production and oxidation of protein thiol
      groups. In addition, tyrosine nitration and cysteine S-nitrosylation of amino
      acid residues in cellular proteins were observed. The potential use of these
      nanoparticles in antitumor chemotherapy of melanoma is discussed.

PMID- 29378126
TI  - Multiplex Surface Plasmon Resonance Imaging-Based Biosensor for Human Pancreatic
      Islets Hormones Quantification.
AB  - Diabetes arises from secretory defects in vascularized micro-organs known as the
      islets of Langerhans. Recent studies indicated that furthering our understanding
      of the paracrine effect of somatostatin on glucose-induced insulin secretion
      could represent a novel therapeutic avenue for diabetes. While many research
      groups are interested in insulin and glucagon secretion, few are particularly
      focused on studying the paracrine interaction in islets' cells, and none on
      monitoring a secretory fingerprint that contemplates more than two hormones.
      Surface plasmon resonance imaging can achieve high-throughput and multiplexed
      biomolecule quantification, making it an ideal candidate for detection of
      multiple islet's secretion products if arrays of hormones can be properly
      implemented on the sensing surface. In this study, we introduced a multiplex
      surface plasmon resonance imaging-based biosensor for simultaneous quantification
      of insulin, glucagon, and somatostatin. Performing this multiplex biosensing of
      hormones was mainly the result of the design of an antifouling sensing surface
      comprised by a mixed self-assembly monolayer of CH3O-PEG-SH and 16
      mercaptohexadecanoic acid, which allowed it to operate in a complex matrix such
      as an islet secretome. The limit of detection in multiplex mode was 1 nM for
      insulin, 4 nM for glucagon, and 246 nM for somatostatin with a total analysis
      time of 21 min per point, making our approach the first reporting a label-free
      and multiplex measurement of such a combination of human hormones. This biosensor
      holds the promise of providing us with a mean for the further understanding of
      the paracrine effect of somatostatin on glucose-induced insulin secretion and
      consequently help develop novel therapeutic agents for diabetes.

PMID- 29378128
TI  - Bile Acid-Based Drug Delivery Systems for Enhanced Doxorubicin Encapsulation:
      Comparing Hydrophobic and Ionic Interactions in Drug Loading and Release.
AB  - Doxorubicin (Dox) is a drug of choice in the design of drug delivery systems
      directed toward breast cancers, but is often limited by loading and control over
      its release from polymer micelles. Bile acid-based block copolymers present
      certain advantages over traditional polymer-based systems for drug delivery
      purposes, since they can enable a higher drug loading via the formation of a
      reservoir through their aggregation process. In this study, hydrophobic and
      electrostatic interactions are compared for their influence on Dox loading inside
      cholic acid based block copolymers. Poly(allyl glycidyl ether) (PAGE) and
      poly(ethylene glycol) (PEG) were grafted from the cholic acid (CA) core yielding
      a star-shaped block copolymer with 4 arms (CA-(PAGE- b-PEG)4) and then loaded
      with Dox via a nanoprecipitation technique. A high Dox loading of 14 wt % was
      achieved via electrostatic as opposed to hydrophobic interactions with or without
      oleic acid as a cosurfactant. The electrostatic interactions confer a pH
      responsiveness to the system. 50% of the loaded Dox was released at pH 5 in
      comparison to 12% at pH 7.4. The nanoparticles with Dox loaded via hydrophobic
      interactions did not show such a pH responsiveness. The systems with Dox loaded
      via electrostatic interactions showed the lowest IC50 and highest cellular
      internalization, indicating the pre-eminence of this interaction in Dox loading.
      The blank formulations are biocompatible and did not show cytotoxicity up to 0.17
      mg/mL. The new functionalized star block copolymers based on cholic acid show
      great potential as drug delivery carriers.

PMID- 29378127
TI  - Electrocatalytic H2O Reduction with f-Elements: Mechanistic Insight and
      Overpotential Tuning in a Series of Lanthanide Complexes.
AB  - Electrocatalytic energy conversion with molecular f-element catalysts is still in
      an early phase of its development. We here report detailed electrochemical
      investigations on the recently reported trivalent lanthanide coordination
      complexes [((Ad,MeArO)3mes)Ln] (1-Ln), with Ln = La, Ce, Pr, Nd, Sm, Gd, Dy, Er,
      and Yb, which were now found to perform as active electrocatalysts for the
      reduction of water to dihydrogen. Reactivity studies involving complexes 1-Ln and
      the Ln(II) analogues [K(2.2.2-crypt)][((Ad,MeArO)3mes)Ln] (2-Ln) suggest a
      reaction mechanism that differs significantly from the reaction pathway found for
      the corresponding uranium catalyst [((Ad,MeArO)3mes)U] (1-U). While complexes 1
      Ln activate water via a radical pathway, only upon a 1 e- reduction to yield the
      reduced species 2-Ln, the 5f analogue 1-U directly reduces H2O via a 2 e-
      pathway. The electrocatalytic H2O reduction by complexes 1-Ln is initiated by the
      respective Ln(III)/Ln(II) redox couples, which gradually turn to more positive
      values across the Ln series. This correlation has been exploited to tune the
      catalytic overpotential of water reduction by choice of the lanthanide ion.
      Kinetic studies of the 1-Ln series were performed to elucidate correlations
      between overpotential and turnover frequencies of the 4f-based electrocatalysts.

PMID- 29378129
TI  - Hybrid Macrocycles for Selective Binding and Sensing of Fluoride in Aqueous
      Solution.
AB  - Synthesis and anion binding properties of hybrid macrocycles containing ammonium
      and hydrogen bond donor groups are reported. Receptor properties were studied in
      a 10 mM MES buffer solution at pH 6.2, at which the receptors carry two positive
      charges at the secondary amine groups. Receptor 1 was found to bind fluoride with
      the highest affinity (105 M-1) and selectivity among the synthesized receptors.
      It was the only receptor that demonstrated fluorescence increase upon addition of
      fluoride. Other titration experiments with halides and oxyanions led to an anion
      induced aggregation and fluorescence quenching. The mechanism of the particular
      turn-on fluorescence for fluoride was explained by the ability of receptor 1 to
      encapsulate several fluoride anions. Multiple anion coordination resulted in the
      protonation of the tertiary amine group and subsequent hindering of the PET
      process. 1H and 19F NMR titrations, single-crystal X-ray structure of chloride
      complex, and DFT calculation suggest that 1 can perfectly accommodate two
      fluoride anions in the inner cavity but only one chloride, keeping the second
      chloride in the outer coordination sphere. Thus, the importance of size
      selectivity, which is reflected in a collective behavior of molecules in an
      aqueous solution, represents a new strategy for the design of highly selective
      probes for fluoride functioning in an aqueous solution.

PMID- 29378130
TI  - Alcalase Enzymolysis of Red Bean (adzuki) Ferritin Achieves Nanoencapsulation of
      Food Nutrients in a Mild Condition.
AB  - Classical methods to fabricate ferritin-nutrients shell-core nanoparticles
      usually apply extremely acid/alkaline pH transition, which may cause the activity
      loss of nutrients or the formation of insoluble aggregates. In this work, we
      prepared an extension peptide (EP) deleted red bean (adzuki) ferritin
      (apoRBFDeltaEP) by Alcalase 3.0T enzymolysis. Such enzymolysis could delete the
      EP domain and remain the typical shell-like structure of the ferritin. Meanwhile,
      the alpha-helix content of apoRBFDeltaEP was decreased by 5.5%, and the
      transition temperature (Tm) was decreased by 4.1  degrees C. Interestingly, the
      apoRBFDeltaEP can be disassembled into subunits under a benign condition at pH
      4.0 and is assembled to form an intact cage protein when the pH was increased to
      6.7. By using this novel route, the epigallocatechin gallate (EGCG) molecules
      were successfully encapsulated into the apoRBFDeltaEP cage with an encapsulation
      ratio of 11.6% (w/w), which was comparable with that by the traditional pH 2.0
      transition. The newly prepared EGCG-loaded apoRBFDeltaEP exhibited a similarly
      protective effect on the EGCG upon simulated gastrointestinal tract and thermal
      treatment as compared with the control. In addition, the EGCG-loaded
      apoRBFDeltaEP could significantly relieve the ferritin association induced by pH
      transition, which was superior to traditional method. The thinking of this work
      will be especially suitable for encapsulating pH-sensitive molecules based on
      ferritin in a benign condition.

PMID- 29378132
TI  - Azure C Targets and Modulates Toxic Tau Oligomers.
AB  - Alzheimer's disease (AD) is the most common age-related neurodegenerative
      disorder affecting millions of people worldwide. Therefore, finding effective
      interventions and therapies is extremely important. AD is one of over 20
      different disorders known as tauopathies, characterized by the pathological
      aggregation and accumulation of tau, a microtubule-associated protein. Tau
      aggregates are heterogeneous and can be divided into two major groups: large
      metastable fibrils, including neurofibrillary tangles, and oligomers. The
      smaller, soluble and dynamic tau oligomers have been shown to be more toxic with
      more proficient seeding properties for the propagation of tau pathology as
      compared to the fibrillar Paired Helical Filaments (PHFs). Therefore, developing
      small molecules that target and interact with toxic tau oligomers can be
      beneficial to modulate their aggregation pathways and toxicity, preventing
      progression of the pathology. In this study, we show that Azure C (AC) is capable
      of modulating tau oligomer aggregation pathways at micromolar concentrations and
      rescues tau oligomers-induced toxicity in cell culture. We used both biochemical
      and biophysical in vitro techniques to characterize preformed tau oligomers in
      the presence and absence of AC. Interestingly, AC prevents toxicity not by
      disassembling the oligomers but rather by converting them into clusters of
      aggregates with nontoxic conformation.

PMID- 29378131
TI  - Benzoyl Halides as Alternative Precursors for the Colloidal Synthesis of Lead
      Based Halide Perovskite Nanocrystals.
AB  - We propose here a new colloidal approach for the synthesis of both all-inorganic
      and hybrid organic-inorganic lead halide perovskite nanocrystals (NCs). The main
      limitation of the protocols that are currently in use, such as the hot injection
      and the ligand-assisted reprecipitation routes, is that they employ PbX2 (X = Cl,
      Br, or I) salts as both lead and halide precursors. This imposes restrictions on
      being able to precisely tune the amount of reaction species and, consequently, on
      being able to regulate the composition of the final NCs. In order to overcome
      this issue, we show here that benzoyl halides can be efficiently used as halide
      sources to be injected in a solution of metal cations (mainly in the form of
      metal carboxylates) for the synthesis of APbX3 NCs (in which A = Cs+, CH3NH3+, or
      CH(NH2)2+). In this way, it is possible to independently tune the amount of both
      cations and halide precursors in the synthesis. The APbX3 NCs that were prepared
      with our protocol show excellent optical properties, such as high
      photoluminescence quantum yields, low amplified spontaneous emission thresholds,
      and enhanced stability in air. It is noteworthy that CsPbI3 NCs, which
      crystallize in the cubic alpha phase, are stable in air for weeks without any
      postsynthesis treatment. The improved properties of our CsPbX3 perovskite NCs can
      be ascribed to the formation of lead halide terminated surfaces, in which Cs
      cations are replaced by alkylammonium ions.

PMID- 29378133
TI  - Quantum Dots Applied to Methodology on Detection of Pesticide and Veterinary Drug
      Residues.
AB  - The pesticide and veterinary drug residues brought by large-scale agricultural
      production have become one of the issues in the fields of food safety and
      environmental ecological security. It is necessary to develop the rapid,
      sensitive, qualitative and quantitative methodology for the detection of
      pesticide and veterinary drug residues. As one of the achievements of
      nanoscience, quantum dots (QDs) have been widely used in the detection of
      pesticide and veterinary drug residues. In these methodology studies, the used QD
      signal styles include fluorescence, chemiluminescence, electrochemical
      luminescence, photoelectrochemistry, etc. QDs can also be assembled into sensors
      with different materials, such as QD-enzyme, QD-antibody, QD-aptamer, and QD
      molecularly imprinted polymer sensors, etc. Plenty of study achievements in the
      field of detection of pesticide and veterinary drug residues have been obtained
      from the different combinations among these signals and sensors. They are
      summarized in this paper to provide a reference for the QD application in the
      detection of pesticide and veterinary drug residues.

PMID- 29378134
TI  - Toll-like Receptor Agonist Conjugation: A Chemical Perspective.
AB  - Toll-like receptors (TLRs) are vital elements of the mammalian immune system that
      function by recognizing pathogen-associated molecular patterns (PAMPs), bridging
      innate and adaptive immunity. They have become a prominent therapeutic target for
      the treatment of infectious diseases, cancer, and allergies, with many TLR
      agonists currently in clinical trials or approved as immunostimulants. Numerous
      studies have shown that conjugation of TLR agonists to other molecules can
      beneficially influence their potency, toxicity, pharmacokinetics, or function.
      The functional properties of TLR agonist conjugates, however, are highly
      dependent on the ligation strategy employed. Here, we review the chemical
      structural requirements for effective functional TLR agonist conjugation. In
      addition, we provide similar analysis for those that have yet to be conjugated.
      Moreover, we discuss applications of covalent TLR agonist conjugation and their
      implications for clinical use.

PMID- 29378135
TI  - Novel Brassinosteroid-Modified Polyethylene Glycol Micelles for Controlled
      Release of Agrochemicals.
AB  - Two synthetic analogues of brassinosteroids (DI31 and S7) exhibit good plant
      growth enhancer activity. However, their hydrophobicity and quick metabolism in
      plants have limited their application and benefits in agriculture. Our objective
      was to prepare novel brassinosteroid-modified polyethylene glycol (PEG) micelles
      to achieve controlled release with extended stability while retaining
      agrochemical activity. Spectroscopic studies confirmed quantitative
      disubstitution of studied PEGs with the brassinosteroids, while elemental
      analysis assessed purity of the synthesized conjugates. Conjugates were also
      characterized by X-ray diffraction and thermal analysis. Dynamic and static light
      scattering showed stable and homogeneous approximately spherical micelles with
      average hydrodynamic diameters of 22-120 nm and almost neutral zeta potential.
      Spherical 30-140 nm micelles were observed by electron microscopy. Sustained in
      vitro releases at pH 5.5 were extended up to 96 h. Prepared PEG micelles showed
      good agrochemical activity in the radish seed bioassay and no cytotoxicity to the
      human microvascular endothelial cell line in the MTS test.

PMID- 29378136
TI  - Fully Flexible Docking via Reaction-Coordinate-Independent Molecular Dynamics
      Simulations.
AB  - Predicting the geometry of protein-ligand binding complexes is of primary
      importance for structure-based drug discovery. Molecular dynamics (MD) is
      emerging as a reliable computational tool for use in conjunction with, or an
      alternative to, docking methods. However, simulating the protein-ligand binding
      process often requires very expensive simulations. This drastically limits the
      practical application of MD-based approaches. Here, we propose a general
      framework to accelerate the generation of putative protein-ligand binding modes
      using potential-scaled MD simulations. The proposed dynamical protocol has been
      applied to two pharmaceutically relevant systems (GSK-3beta and the N-terminal
      domain of HSP90alpha). Our approach is fully independent of any predefined
      reaction coordinate (or collective variable). It identified the correct binding
      mode of several ligands and can thus save valuable computational time in dynamic
      docking simulations.

PMID- 29378137
TI  - Metabolomics Uncovers the Regulatory Pathway of Acyl-homoserine Lactones Based
      Quorum Sensing in Anammox Consortia.
AB  - Acyl-homoserine lactones (AHLs)-mediated quorum sensing in bacterial communities
      have been extensively observed. However, the metabolic pathways regulated by AHLs
      in bacteria remain elusive. Here, we combined long-term reactor operation with
      microbiological and metabolomics analyses to explore the regulatory pathways for
      different AHLs in anammox consortia, which perform promising nitrogen removal for
      wastewater treatment. The results showed that no obvious shifts induced by
      exogenous AHLs occurred in the microbial community and, mainly, dosing AHLs
      induced changes in the metabolites. 3OC6-HSL, C6-HSL, and C8-HSL controlled the
      electron transport carriers that influence the bacterial activity. In contrast,
      only 3OC6-HSL regulated LysoPC(20:0) metabolism, which affected bacterial growth.
      AHLs mainly regulated the synthesis of the amino acids Ala, Val, and Glu and
      selectively regulated Asp and Leu to affect extracellular proteins.
      Simultaneously, all the AHLs regulated the ManNAc biosynthetic pathways, while
      OC6-HSL, OC8-HSL, and C6-HSL particularly enriched the UDP-GlcNAc pathway to
      promote exopolysaccharides, resulting in different aggregation levels of the
      anammox consortia. Our results not only provide the first metabolic insights into
      the means by which AHLs affect anammox consortia but also hint at potential
      strategies for overcoming the limitations of the long start-up period required
      for wastewater treatment by anammox processing.

PMID- 29378138
TI  - Phe71 in Type III Trypanosomal Protein Arginine Methyltransferase 7 (TbPRMT7)
      Restricts the Enzyme to Monomethylation.
AB  - Protein arginine methyltransferase 7 (PRMT7) is unique within the PRMT family as
      it is the only isoform known to exclusively make monomethylarginine (MMA). Given
      its role in epigenetics, the mechanistic basis for the strict monomethylation
      activity is under investigation. It is thought that PRMT7 enzymes are unable to
      add a second methyl group because of steric hindrance in the active site that
      restricts them to monomethylation. To test this, we probed the active site of
      trypanosomal PRMT7 (TbPRMT7) using accelerated molecular dynamics, site-directed
      mutagenesis, kinetic, binding, and product analyses. Both the dynamics
      simulations and experimental results show that the mutation of Phe71 to Ile
      converts the enzyme from a type III methyltransferase into a mixed type I/II,
      that is, an enzyme that can now perform dimethylation. In contrast, the serine
      and alanine mutants of Phe71 preserve the type III behavior of the native enzyme.
      These results are inconsistent with a sterics-only model to explain product
      specificity. Instead, molecular dynamics simulations of these variants bound to
      peptides show hydrogen bonding between would-be substrates and Glu172 of TbPRMT7.
      Only in the case of the Phe71 to Ile mutation is this interaction between MMA and
      the enzyme maintained, and the geometry for optimal SN2 methyl transfer is
      obtained. The results of these studies highlight the benefit of combined
      computational and experimental methods in providing a better understanding for
      how product specificity is dictated by PRMTs.

PMID- 29378139
TI  - Coil-Globule Collapse of Polystyrene Chains in Tetrahydrofuran-Water Mixtures.
AB  - We study the coil and globule states of a single polymer chain in solution by
      performing molecular dynamics simulations with a united atom model. Specifically,
      we characterize the structural properties of atactic polystyrene chains with N =
      20-150 monomers in tetrahydrofuran-water mixtures at varying mixing ratios. We
      find that the hydrophobic polymers form rather open coils when the mole fraction
      of water, XW, is roughly below 0.25, whereas the chains collapse into globules
      when XW ? 0.75. We confirm the theoretically expected scaling laws for the radius
      of gyration, Rg, in these regimes, i.e., Rg ? N3/5 and Rg ? N1/3 for good and
      poor solvent conditions, respectively. For poor solvent conditions with XW =
      0.75, we find a sizable fraction of residual tetrahydrofuran trapped inside the
      collapsed polymer chains with an excess amount located at the globule surface,
      acting as a protective layer between the hydrophobic polystyrene and the
      surrounding water-rich mixture. These findings have important implications for
      nanoparticle fabrication techniques where solvent exchange is exploited to drive
      polymer aggregation, since residual solvent can significantly influence the
      physical properties of the precipitated nanoparticles.

PMID- 29378140
TI  - Allosteric Modulation of Human Hsp90alpha Conformational Dynamics.
AB  - Central to Hsp90's biological function is its ability to interconvert between
      various conformational states. Drug targeting of Hsp90's regulatory mechanisms,
      including its modulation by cochaperone association, presents as an attractive
      therapeutic strategy for Hsp90 associated pathologies. In this study, we utilized
      homology modeling techniques to calculate full-length structures of human
      Hsp90alpha in closed and partially open conformations and used these structures
      as a basis for several molecular dynamics based analyses aimed at elucidating
      allosteric mechanisms and modulation sites in human Hsp90alpha. Atomistic
      simulations demonstrated that bound adenosine triphosphate (ATP) stabilizes the
      dimer by "tensing" each protomer, while adenosine diphosphate (ADP) and apo
      configurations "relax" the complex by increasing global flexibility, the former
      case resulting in a fully open "v-like" conformation. Dynamic residue network
      analysis revealed regions of the protein involved in intraprotein communication
      and identified several key communication hubs that correlate with known
      functional sites. Pairwise comparison of betweenness centrality, shortest path,
      and residue fluctuations revealed that a proportional relationship exists between
      the latter two measurables and an inverse relationship between these two and
      betweenness centrality. This analysis showed how protein flexibility, degree of
      compactness, and the distance cutoff used for network construction influence the
      correlations between these metrics. These findings are novel and suggest shortest
      path and betweenness centrality to be more relevant quantities to follow for
      detecting functional residues in proteins compared to residue fluctuations.
      Perturbation response scanning analysis identified several potential residue
      sites capable of modulating conformational change in favor of interstate
      conversion. For the ATP-bound open conformation, these sites were found to
      overlap with known Aha1 and client binding sites, demonstrating how naturally
      occurring forces associated with cofactor binding could allosterically modulate
      conformational dynamics.

PMID- 29378141
TI  - Quantum-Confined Stark Effect in a MoS2 Monolayer van der Waals Heterostructure.
AB  - The optics of dangling-bond-free van der Waals heterostructures containing
      transition metal dichalcogenides are dominated by excitons. A crucial property of
      a confined exciton is the quantum confined Stark effect (QCSE). Here, such a
      heterostructure is used to probe the QCSE by applying a uniform vertical electric
      field across a molybdenum disulfide (MoS2) monolayer. The photoluminescence
      emission energies of the neutral and charged excitons shift quadratically with
      the applied electric field, provided that the electron density remains constant,
      demonstrating that the exciton can be polarized. Stark shifts corresponding to
      about half the homogeneous linewidth were achieved. Neutral and charged exciton
      polarizabilities of (7.8 +/- 1.0) * 10-10 and (6.4 +/- 0.9) * 10-10 D m V-1 at
      relatively low electron density (~1012 cm-2) have been extracted, respectively.
      These values are one order of magnitude lower than the previously reported values
      but in line with theoretical calculations. The methodology presented here is
      versatile and can be applied to other semiconducting layered materials.

PMID- 29378142
TI  - Intercorrelated In-Plane and Out-of-Plane Ferroelectricity in Ultrathin Two
      Dimensional Layered Semiconductor In2Se3.
AB  - Enriching the functionality of ferroelectric materials with visible-light
      sensitivity and multiaxial switching capability would open up new opportunities
      for their applications in advanced information storage with diverse signal
      manipulation functions. We report experimental observations of robust intralayer
      ferroelectricity in two-dimensional (2D) van der Waals layered alpha-In2Se3
      ultrathin flakes at room temperature. Distinct from other 2D and conventional
      ferroelectrics, In2Se3 exhibits intrinsically intercorrelated out-of-plane and in
      plane polarization, where the reversal of the out-of-plane polarization by a
      vertical electric field also induces the rotation of the in-plane polarization.
      On the basis of the in-plane switchable diode effect and the narrow bandgap (~1.3
      eV) of ferroelectric In2Se3, a prototypical nonvolatile memory device, which can
      be manipulated both by electric field and visible light illumination, is
      demonstrated for advancing data storage technologies.

PMID- 29378143
TI  - Probing Spatiotemporal Stability of Optical Matter by Polarization Modulation.
AB  - Light-driven self-organization of plasmonic nanoparticles via optical binding
      interactions offers a unique route to assemble mesoscale photonic clusters and
      chains. However, stability becomes an issue when more nanoparticles are added
      into the clusters and chains, since the theoretical optical binding strength is
      inhomogeneous and anisotropic in optical matter systems. Here we study the
      spatiotemporal stability of optical matter chains self-organized by two to eight
      ultrauniform gold nanospheres in a linearly polarized optical line trap.
      Perturbations are introduced into the nanosphere chains by periodically switching
      the polarization to be either parallel or perpendicular to the orientation of the
      chains, where the spatial and temporal variation of optical binding strength has
      been revealed. In addition, we found that the average oscillation amplitude and
      stability of the particles can be tuned by the frequency of polarization
      modulation. These results demonstrate a new way to study and improve the
      stability of optical matter and provide a promising strategy in engineering
      optical forces at the mesoscale.

PMID- 29378145
TI  - Assessment of common red blood cell pretreatments to yield an accurate serologic
      antigen phenotype compared with genotypepredicted phenotype.
AB  - CONCLUSIONS: For patients requiring multiple transfusions and patients with
      positive direct antiglobulin tests (DATs), an extended red blood cell (RBC)
      phenotype can provide valuable information and help to determine the risk of
      forming alloantibodies. In some instances, the phenotype may be used for
      prophylactic matching. Phenotyping in this patient population is often hindered
      by the presence of circulating donor cells and/or by a positive DAT. Several
      methods, such as EDTA glycine acid (EGA) treatment to remove IgG, hypotonic
      saline wash to separate autologous RBCs, or reticulocyte separation, are often
      used in these situations to isolate patient RBCs for serologic phenotyping. This
      study aimed to determine the accuracy of each RBC pretreatment method by
      comparing serologically determined antigen types with those predicted by RBC
      genotyping. Forty-eight peripheral blood samples from recently transfused
      patients were phenotyped for selected antigens in the Rh, Kell, MNS, Duffy, and
      Kidd systems. Treatment methods for the sample sets were reticulocyte separation
      (N = 12), EGA (N = 16), and hypotonic saline wash (N = 20). DNA was extracted
      using standard methods, and genotyping was performed using the HEA BeadChip
      panel. In addition, 21 samples positive for RBC-bound IgG were EGAtreated up to
      two times. These samples were analyzed pre- and post-EGA treatment for RBC-bound
      IgG by tube DAT and by flow cytometry with fluorescein isothiocyanate-labeled
      antihuman IgG. After reticulocyte separation, 3 of the 12 samples had discordant
      types with one antigen each: Fyb, N, and K; serologic results were negative
      compared with genotype-predicted positive phenotype results. The EGA-treated
      sample set showed one discordant type: Fyb; serologic results were negative
      compared with genotype-predicted positive phenotype results. Four of the 20
      samples had discordant types involving the following antigens: Fyb, N, e, and M;
      serologic results were negative compared with genotype-predicted positive
      phenotype results. After EGA treatment of 21 samples, 14 (67%) were negative for
      RBC-bound IgG by tube DAT, and 7 remained positive. Using flow cytometry, EGA
      treatment rendered only 4 samples negative, and 17 remained positive. In the
      antigen testing sample set of 48 samples, 10 of 511 total antigen types tested
      were discordant. Discordant types were most frequent in the hypotonic saline wash
      sample set (N = 6). In the flow cytometry sample set, 48 percent of the samples
      negative by tube DAT after EGA elution had detectable RBCbound IgG by flow
      cytometry. These findings suggest that caution should be taken when using
      phenotype results from all pretreated RBCs and support the use of RBC genotyping
      to predict RBC antigen expression in samples from recently transfused patients.

PMID- 29378144
TI  - Biodistribution Analysis of NIR-Labeled Nanogels Using in Vivo FMT Imaging in
      Triple Negative Human Mammary Carcinoma Models.
AB  - The purpose of this study is to evaluate the biodistribution properties of random
      copolymer-based core-cross-linked nanogels of various sizes and surface
      poly(ethylene glycol) composition. Systematic variations of near-IR labeled
      nanogels, comprising varying particle sizes (28-135 nm), PEG corona quantity (0
      50 mol %), and PEG length (PEG Mn 1000, 2000, and 5000), were prepared and
      injected in mice that had been subcutaneously implanted with MDA-MB-231-luc
      D3H2LN human mammary carcinoma. In vivo biodistribution was obtained using
      fluorescence molecular tomography imaging at 0, 6, 24, 48, and 72 h
      postinjection. Retention of total body probe and percentages of total injected
      dose in the tumor, liver, spleen, lungs, heart, intestines, and kidneys were
      obtained. Smaller nanogels (~30-40 nm) with a high PEG conjugation (~43-46 mol %)
      of Mn 2000 on their coronas achieved the highest tumor specificity with peak
      maximum 27% ID/g, a statistically significant propensity toward accumulation with
      16.5% ID/g increase from 0 to 72 h of imaging, which constitutes a 1.5-fold
      increase. Nanogels with greater tumor localization also had greater retention of
      total body probe over 72 h. Nanogels without extensive PEGylation were rapidly
      excreted, even at similar sizes to PEGylated nanogels exhibiting whole body
      retention. Of all tissues, the liver had the highest % ID, however, like other
      tissues, it displayed a monotonic decrease over time, suggesting nanogel
      clearance by hepatic metabolism. Ex vivo quantification of individual tissues
      from gross necropsy at 72 h postinjection generally correlated with the FMT
      analysis, providing confidence in tissue signal segmentation in vivo. The
      parameters determined to most significantly direct a nanogel to the desired tumor
      target can lead to improve effectiveness for nanogels as therapeutic delivery
      vehicles.

PMID- 29378146
TI  - Anti-Vel alloimmunization and severe hemolytic disease of the fetus and newborn.
AB  - CONCLUSIONS: Only rare cases of anti-Vel-associated mild-to-moderate hemolytic
      disease of the fetus and newborn have been previously reported. No case of fetal
      anemia requiring prenatal therapy has been noted to date. We report such a case
      recently encountered at our Fetal Center. Strategies are discussed for managing
      pregnancy complicated with alloimmunization to an antibody to a high-prevalence
      antigen, including sources of red blood cells for intrauterine transfusions.

PMID- 29378147
TI  - Separation of multiple antibodies by adsorption with allogeneic red blood cells.
AB  - CONCLUSIONS: Antibody detection and identification are processes that are
      commonly performed in the transfusion service before transfusion of allogeneic
      red blood cells (RBCs). Antibody identification usually follows the discovery of
      a positive antibody detection test, or other factors such as ABO serum/cell
      discrepancy or an incompatible crossmatch. Antibody identification is a necessary
      practice in blood banking to determine the suitability of blood products for
      transfusion on an individual basis. When the presence of multiple antibodies is
      suspected, several methods, including neutralization of patient's plasma,
      titration, elution, chemical or enzyme treatment of reagent RBCs, and adsorption
      with allogeneic RBCs, may be used to separate and properly identify other
      atypical antibodies that are present in a single serum or plasma sample. This
      review will focus on the use of allogeneic adsorption to identify antibody
      specificities in a patient's sample.

PMID- 29378148
TI  - Hemovigilance and the Notify Library.
AB  - CONCLUSIONS: Hemovigilance systems allow reporting of adverse occurrences
      associated with blood transfusion to a central database where events can be
      reviewed and analyzed for the benefit of patients and donors. Hemolytic and
      serologic transfusion reactions are among the many types of reactions reported to
      these systems. The Notify Library, a database of adverse events associated with
      medical products of human origin, has incorporated hemovigilance into its
      didactic resources. Students and practitioners are encouraged to use the
      electronic library and to further enhance this resource through review and
      recommendation of additional publications in the area of immunohematology.

PMID- 29378149
TI  - Clinical and laboratory profile of anti-M.
AB  - CONCLUSIONS: Anti-M is a frequently detected naturally occurring antibody that
      has been reported in various clinical settings and also in voluntary donors. We
      describe here the clinical and laboratory findings of 11 cases with anti-M
      detected at our center. This report is a retrospective study in which we reviewed
      our immunohematology laboratory records for cases involving anti-M. Both donor
      and patient data from a 28-month period (September 2014 to December 2016) were
      reviewed. During this period, 11 examples of anti-M were detected (8 patients, 1
      voluntary whole blood donor, and 1 hematopoietic stem cell donor. Anti-M was also
      detected in one external quality assessment scheme sample received during this
      period. In conclusion, anti-M can be detected in various clinical settings. This
      antibody can be clinically significant; in the laboratory, it can present as a
      serologic problem such as an ABO group discrepancy or an incompatible crossmatch.
      After detection, management and course of action is determined by both the
      antibody characteristics and the clinical setting.

PMID- 29378150
TI  - Dithiothreitol treatment of red blood cells.
AB  - CONCLUSIONS: Dithiothreitol (DTT), a reducing reagent, has multiple applications
      in blood bank testing. DTT disrupts the bridging of the disulfide bonds between
      amino acid residues necessary for structural conformation of some proteins and
      the bonds holding an IgM molecule in the pentameric formation. DTT treatment of
      red blood cells (RBCs) can denature or modify certain blood group antigens-in
      particular, those in the Kell, Lutheran, YT, JMH, LW, Cromer, Indian, Dombrock,
      and Knops systems-and prevent recognition by the corresponding antibodies. It
      also destroys RBC CD38, allowing DTT-treated RBCs to be used to avoid testing
      interference by therapeutic anti-CD38 preparations. DTT treatment can be used to
      disperse spontaneous agglutination of RBCs caused by heavy IgM autoantibody
      coating that invalidates ABO/Rh cell grouping and direct antiglobulin tests.

PMID- 29378151
TI  - What Happens after a Diagnosis of High-Risk Breast Lesion at Stereotactic Vacuum
      assisted Biopsy? An Observational Study of Postdiagnosis Management and Imaging
      Adherence.
AB  - Purpose To assess adherence with annual or biennial screening mammography after a
      diagnosis of high-risk lesion(s) at stereotactic biopsy with or without surgical
      excision and to identify clinical factors that may affect screening adherence
      after a high-risk diagnosis. Materials and Methods This institutional review
      board-approved HIPAA-compliant retrospective study included 208 patients who
      underwent stereotactic biopsy between January 2012 and December 2014 that
      revealed a high-risk lesion. Whether the patient underwent surgical excision
      and/or follow-up mammography was documented. Adherence of these women to a
      protocol of subsequent mammography within 1 year (9-18 months) or within 2 years
      (9-30 months) was compared with that of 45 508 women with normal screening
      mammograms who were imaged during the same time period at the same institution.
      Possible factors relevant to postdiagnosis management and screening adherence
      were assessed. Consultation with a breast surgeon was identified by reviewing
      clinical notes. Uptake of pharmacologic chemoprevention following diagnosis
      (patient decision to take chemopreventive medications) was assessed. The Fisher
      exact test was used to compare annual or biennial screening adherence rates.
      Binary logistic regression was used to identify factors predictive of whether
      women returned for screening within selected time frames. Results In total, 913
      (1.3%) of 67 874 women were given a recommendation to undergo stereotactic
      biopsy, resulting in diagnosis of 208 (22.8%) of 913 high-risk lesions. Excluding
      those with a prior personal history of breast cancer or upgrade to cancer at
      surgery, 124 (66.7%) of 186 women underwent surgery and 62 (33.3%) did not.
      Overall post-high-risk diagnosis adherence to annual or biennial mammography was
      similar to that in control subjects (annual, 56.4% vs 50.8%, P = .160; biennial,
      62.0% vs 60.1%, P = .630). Adherence was significantly better in the surgical
      group than in the nonsurgical group for annual mammography (70.0% vs 32.0%; odds
      ratio [OR] = 5.0; 95% confidence interval [CI]: 2.4, 10.1; P < .001) and for
      biennial mammography (74.3% vs 40.0%; OR = 4.3; 95% CI: 2.1, 8.8; P < .001).
      Among the patients in the nonsurgical group, those adherent to annual or biennial
      mammography were significantly more likely to have seen a breast surgeon than the
      nonadherent women (annual, 77.3% vs 35.7%, P = .005; biennial, 67.9% vs 36.4%, P
      = .045). All patients receiving chemopreventive agents underwent a surgical
      consultation (100%; n = 21). Conclusion Although diagnosis of a high-risk lesion
      at stereotactic breast biopsy did not compromise overall adherence to subsequent
      mammographic screening, patients without surgical excision, particularly those
      who did not undergo a surgical consultation, had significantly lower imaging
      adherence and chemoprevention uptake as compared with their counterparts who
      underwent surgery, suggesting that specialist care may be important in optimizing
      management. (c) RSNA, 2018.

PMID- 29378152
TI  - Beneficial effects of N-acetylcysteine on hepatic oxidative stress in
      streptozotocin-induced diabetic rats.
AB  - Diabetes is one of the leading diseases worldwide and, thus, finding new
      therapeutic alternatives is essential. The development of non-alcoholic fatty
      liver disease is a notable diabetic complication. Therefore, antioxidant therapy
      became a leading topic in the world of diabetes research. The objective of this
      present study was to evaluate the effects of antioxidant N-acetylcysteine (NAC)
      administration on serum biochemical parameters and oxidative stress parameters in
      hepatic tissue of the diabetic rats. Thirty-two animals were divided in 4 groups
      (n = 8): G1, normal rats; G2, normal rats + NAC; G3, diabetic rats; and G4,
      diabetic rats + NAC. Diabetes was induced in diabetic groups through
      streptozotocin. NAC administration was effective in improving hyperglycemia and
      hypoinsulinemia, as well as reducing serum alanine-aminotransferase and urea,
      hepatic triglycerides accumulation, and oxidative stress biomarkers in the
      diabetic liver, as well as improving the activity of hepatic antioxidant enzymes.
      This effect was likely due to NAC's ability of restoring intracellular
      glutathione, an important compound for the antioxidant defense, as well as due to
      NAC's direct antioxidant properties. Thus, NAC administration was useful for
      reducing hepatic oxidative stress and decreased the deposit of triacylglycerols,
      minimizing diabetic hepatic damage, making it a promising therapeutic adjuvant in
      the future.

PMID- 29378153
TI  - Curcumin supplementation ameliorated vascular dysfunction and improved
      antioxidant status in rats fed a high-sucrose, high-fat diet.
AB  - Vascular endothelial dysfunction is a potential risk factor for cardiovascular
      disease. This study evaluated the effect of curcumin on factors associated with
      vascular dysfunction using rats fed a high-sucrose, high-fat (HSF) diet. The
      experiment included 2 animal feeding phases. In the first feeding phase, male
      Sprague-Dawley rats were randomly divided into 2 groups: the control group (n =
      8) was fed a standard diet (AIN-93G) and the HSF group (n = 24) was fed an HSF
      diet for 8 weeks to induce obesity. In the second feeding phase, lasting 4 weeks,
      the HSF group was randomly divided into 3 subgroups: the O group (n = 8)
      continued feeding on the HSF diet, the OA group (n = 8) had the HSF diet replaced
      with AIN-93G, and the OC group (n = 8) was fed the HSF diet supplemented with
      curcumin (300 mg/kg body weight daily). After 8 weeks, the HSF diet significantly
      elevated levels of aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), insulin, homeostatic model assessment insulin resistance (HOMA-IR), low
      density lipoprotein cholesterol (LDL-C), homocysteine (Hcy), C-reactive protein
      (CRP), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion
      molecule 1 (ICAM-1) but significantly reduced levels of nitric oxide (NO) and
      high-density lipoprotein cholesterol (HDL-C). After dietary intervention, the OA
      and OC groups exhibited significantly lower levels of AST, ALT, HOMA-IR,
      cholesterol, LDL-C, Hcy, CRP, VCAM-1, and ICAM-1 and higher levels of NO and
      catalase (CAT) activity compared with the O group. Superoxide dismutase, CAT, and
      glutathione peroxidase activities were increased in the OA group, while CAT
      levels were enhanced in the OC group. In conclusion, this study showed that
      curcumin supplementation and diet modification can inhibit HSF diet-induced
      vascular dysfunction potentially by enhancing NO production and antioxidant
      enzyme activities, thereby suppressing inflammation and oxidative damage in the
      vascular endothelium.

PMID- 29378154
TI  - Plasma dispositions and concentrations of ivermectin in eggs following treatment
      of laying hens.
AB  - AIMS: To determine the plasma disposition and concentrations of ivermectin (IVM)
      in eggs produced by laying hens following S/C, oral and I/V administration.
      METHODS: Twenty-four laying hens, aged 37 weeks and weighing 1.73 (SD 0.12) kg
      were allocated to three groups of eight birds. The injectable formulation of IVM
      was administered either orally, S/C, or I/V, at a dose of 0.2 mg/kg liveweight,
      following dilution (1:5, v/v) with propylene glycol. Heparinised blood samples
      were collected at various times between 0.25 hours and 20 days after drug
      administration. Eggs produced by hens were also collected daily throughout the
      study period. Samples of plasma and homogenised egg were analysed using HPLC.
      RESULTS: Maximum concentrations of IVM in plasma and mean residence time of IVM
      were lower after oral (10.2 (SD 7.2) ng/mL and 0.38 (SD 0.14) days, respectively)
      than after S/C (82.9 (SD 12.4) ng/mL and 1.05 (SD 0.24) days, respectively)
      administration (p<0.01). The time to maximum concentration and elimination half
      life were shorter following oral (0.14 (SD 0.04) and 0.23 (SD 0.11) days,
      respectively) than S/C (0.25 (SD 0.00) and 1.45 (SD 0.45) days, respectively)
      administration (p<0.01). IVM was first detected in eggs 2 days after treatment in
      all groups and was detected until 8 days after oral and I/V administration, and
      until 15 days after S/C administration. Peak concentrations of IVM were 15.7,
      23.3 and 1.9 ug/kg, observed 2, 5 and 4 days after I/V, S/C and oral
      administration, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The low plasma
      bioavailability of IVM observed after oral administration in laying hens could
      result in lower efficacy or subtherapeutic plasma concentrations, which may
      promote the development of parasitic drug resistance. Due to high IVM residues in
      eggs compared to the maximum residue limits for other food-producing animal
      species, a withdrawal period should be necessary for eggs after IVM treatment in
      laying hens.

PMID- 29378155
TI  - Reliability of the individual components of the Canadian Armed Forces Physical
      Employment Standard.
AB  - This investigation recruited 24 participants from both the Canadian Armed Forces
      (CAF) and civilian populations to complete 4 separate trials at "best effort" of
      each of the 4 components in the CAF Physical Employment Standard named the FORCE
      Evaluation: Fitness for Operational Requirements of CAF Employment. Analyses were
      performed to examine the level of variability and reliability within each
      component. The results demonstrate that candidates should be provided with at
      least 1 retest if they have recently completed at least 2 previous best effort
      attempts as per the protocol. In addition, the minimal detectable difference is
      given for each of the 4 components in seconds which identifies the threshold for
      subsequent action, either retest or remedial training, for those unable to meet
      the minimum standard. These results will educate the delivery of this employment
      standard, function as a method of accommodation, in addition to providing
      direction for physical training programs.

PMID- 29378157
TI  - Errata.

PMID- 29378156
TI  - Pseudo-Infected Red Blood Cell Beads as Positive Control for Cell Microarray Chip
      Based Detection of Plasmodium-Infected RBCs.
AB  - The cell microarray chip is a polystyrene plate with 20,944 microchambers, and it
      is used to detect red blood cells (RBCs) infected with the causative agent of
      malaria, Plasmodium. Plasmodium-infected red blood cells (iRBCs) stained with a
      nuclear staining dye (SYTO 21) form a monolayer on the bottom of the
      microchambers, and about 130 RBCs are accommodated in each such microchamber of
      the chip. The iRBCs in the RBC monolayer (containing 2.7 million RBCs) can be
      identified using a fluorescence detector, and the infection rate can be
      calculated by counting the number of fluorescent-positive RBCs. This diagnostic
      device is highly sensitive and hence advantageous for early diagnosis of malaria
      infections in endemic areas. However, a standard positive control for Plasmodium
      infected RBCs is required to ensure that the reagents and detectors of these cell
      microarray chips are working efficiently in remote endemic areas. Here, we
      introduce "pseudo-iRBC beads," which consist of a mixture of DEA beads mimicking
      RBCs and DEA beads coated with nucleic acids mimicking nuclei of the parasite.
      These beads can be stained with SYTO 21, applied onto the cell microarray chip to
      form a monolayer, and detected using the fluorescence detector in the same way as
      iRBCs. Therefore, the introduction of pseudo-iRBC beads as a positive control
      ensures unbiased malaria diagnoses with the cell microarray chip device in remote
      endemic areas.

PMID- 29378158
TI  - Errata.

PMID- 29378159
TI  - Erratum to: Upstream signalling of mTORC1 and its hyperactivation in type 2
      diabetes (T2D).
AB  - The original version of this article unfortunately contained typographical errors
      in the text and figures. This article has been updated to correct these errors as
      red highlighting in this pages.

PMID- 29378160
TI  - Distinct Presentation of a Neglected Tropical Disease on Screening Colonoscopy.

PMID- 29378161
TI  - Rational redesign of the ferredoxin-NADP+-oxido-reductase/ferredoxin-interaction
      for photosynthesis-dependent H2-production.
AB  - Utilization of electrons from the photosynthetic water splitting reaction for the
      generation of biofuels, commodities as well as application in biotransformations
      requires a partial rerouting of the photosynthetic electron transport chain. Due
      to its rather negative redox potential and its bifurcational function, ferredoxin
      at the acceptor side of Photosystem 1 is one of the focal points for such an
      engineering. With hydrogen production as model system, we show here the impact
      and potential of redox partner design involving ferredoxin (Fd), ferredoxin-oxido
      reductase (FNR) and [FeFe]-hydrogenase HydA1 on electron transport in a future
      cyanobacterial design cell of Synechocystis PCC 6803. X-ray-structure-based
      rational design and the allocation of specific interaction residues by NMR
      analysis led to the construction of Fd- and FNR-mutants, which in appropriate
      combination enabled an about 18-fold enhanced electron flow from Fd to HydA1 (in
      competition with equimolar amounts of FNR) in in vitro assays. The negative
      impact of these mutations on the Fd-FNR electron transport which indirectly
      facilitates H2 production (with a contribution of <=42% by FNR variants and <=23%
      by Fd-variants) and the direct positive impact on the Fd-HydA1 electron transport
      (<=23% by Fd-mutants) provide an excellent basis for the construction of a
      hydrogen-producing design cell and the study of photosynthetic efficiency
      optimization with cyanobacteria.

PMID- 29378162
TI  - Effects of cerium oxide nanoparticles on differentiated/undifferentiated human
      intestinal Caco-2 cells.
AB  - Since ingestion constitute one of the main routes of nanoparticles (NPs)
      exposure, intestinal cells seems to be a suitable choice to evaluate their
      potential harmful effects. Caco-2 cells, derived from a human colon
      adenocarcinoma, have the ability to differentiate forming consistent cell
      monolayer structures. For these reasons Caco-2 cells, both in their
      undifferentiated or differentiated state, are extendedly used. We have used well
      structured monolayers of differentiated Caco-2 cells, as a model of intestinal
      barrier, to evaluate potential harmful effects associated to CeO2NPs exposure via
      ingestion. Different parameters such as cell toxicity, monolayer integrity and
      permeability, cell internalization, translocation through the monolayer, and
      induction of DNA damage were evaluated. No toxic effects of CeO2NPs were
      observed, independently of the differentiated state of the Caco-2 cells. In the
      same way, no effects on the monolayer integrity/permeability were observed.
      Although important cell uptake was demonstrated in undifferentiated cells (by
      using confocal microscopy), CeO2NPs remained mostly attached to the apical
      membrane in the differentiated cells. In spite of this apparent lack of uptake in
      differentiated cells, translocation of CeO2NPs to the basolateral chamber was
      observed by using confocal microscopy. Finally no genotoxic effects were observed
      when the comet assay was used, although decreases in the levels of oxidized bases
      were observed, supporting the antioxidant role of CeO2NPs.

PMID- 29378163
TI  - Microparticles as prognostic biomarkers in dengue virus infection.
AB  - Promising biomarkers which may help predict the risk of developing severe dengue
      virus infection (DVI) are lacking and will be helpful. Thus the main aim of this
      study was to analyze the role of cell-derived microparticles (MP) in DVI. Sixty
      patients with DVI i.e. 18: dengue with warning signs (DWS); 1: DSS and 41: dengue
      without warning signs (DWOS); along with 15 controls (other febrile illness) were
      included in the study. The following MPs were assessed: annexinV, platelet
      (CD41a), red blood cell (RBC) (CD235a) and activated endothelial (CD62e) MPs.
      Patients with profound thrombocytopenia without bleeding had statistically
      elevated platelet MP (PMP) levels when compared to patients with profound
      thrombocytopenia with bleeding (p < .001). RBC MPs were found to be significantly
      elevated in the 2nd phase in patient with DWS which was seen earliest on day 4 of
      infection with a cut off of  >=2200 MPs/MUl when compared to patients with DWOS
      (p < .0001). PMPs may prove to be a promising novel biomarker which helps
      discriminate patients in need of prophylactic platelet transfusion from those who
      do not. RBC MPs, on the other hand could be potential biomarkers capable of
      identifying potentially severe patients who require immediate care. Thus, MPs
      seem to be a promising important biomarker in many aspects of DVI.

PMID- 29378165
TI  - SAXS and homology modelling based structure characterization of pectin
      methylesterase a family 8 carbohydrate esterase from Clostridium thermocellum
      ATCC 27405.
AB  - Pectin methylesterase (CtPME) from Clostridium thermocellum of family 8
      carbohydrate esterase (CE8) belongs to pectin methylesterase super family
      (E.C.3.1.1.11). BLAST analysis of CtPME showed 38% sequence identity with PME
      from Erwinia chrysanthemi. Multiple sequence alignment of CtPME with other known
      structures of pectin methylesterase revealed the conserved and semi-conserved
      amino acid residues. Homology modelling of CtPME structure revealed a
      characteristic right handed parallel beta-helices. The energy of modelled
      structure was minimized by using YASARA software. The Ramachandran plot of CtPME
      shows 83.7% residues in non-glycine and non-proline residues in most-favorable
      region, 13.8% in additional allowed region and 1.4% in generously allowed region,
      indicating that CtPME has a stable conformation. The secondary structure of CtPME
      predicted using PSI-Pred software and confirmed by the circular dichroism (CD)
      showed alpha-helices (3.1%), beta-sheets (40.1%) and random coils (56.9%). Small
      Angle X-ray Scattering (SAXS) analysis demonstrated the overall shape and
      structural characterization of CtPME in solution form. Guinier analysis gave the
      radius of gyration (Rg) 2.28 nm for globular shape and 0.74 nm for rod shape.
      Kratky plot gave the indication that protein is fully folded in solution. The ab
      initio derived dummy atom model of CtPME superposed well on modelled CtPME
      structure.

PMID- 29378164
TI  - The chlorinated lipidome originating from myeloperoxidase-derived HOCl targeting
      plasmalogens: Metabolism, clearance, and biological properties.
AB  - Myeloperoxidase produces the two-electron oxidant HOCl, which targets plasmalogen
      phospholipids liberating 2-chlorofatty aldehyde. 2-Chlorofatty aldehyde has four
      known fates: 1) oxidation to 2-chlorofatty acid; 2) reduction to 2-chlorofatty
      alcohol; 3) Schiff base adduct formation with proteins and amines; and 4)
      reactivity with glutathione through nucleophilic attack of the alpha-chlorinated
      carbon. 2-Chlorofatty acid does not undergo conventional fatty acid beta
      oxidation due to the presence of the alpha-chlorinated carbon; however, 2
      chlorofatty acid does undergo sequential omega-oxidation and beta-oxidation from
      the omega-end, ultimately resulting in 2-chloroadipic acid urinary excretion.
      Recent studies have demonstrated that 2-chlorofatty acid clearance is increased
      by treatment with the PPAR-alpha agonist WY14643, which increases the enzymatic
      machinery responsible for hepatic omega-oxidation. Furthermore, 2-chlorofatty
      acid has been shown to be a PPAR-alpha agonist, and thus accelerates its own
      clearance. The roles of 2-chlorofatty aldehyde and 2-chlorofatty acid on
      leukocyte and endothelial function have been explored by several groups,
      suggesting that chlorinated lipids induce endothelial cell dysfunction,
      neutrophil chemotaxis, monocyte apoptosis, and alterations in vascular tone.
      Thus, the chlorinated lipidome, produced in response to leukocyte activation, is
      a potential biomarker and therapeutic target to modulate host response in
      inflammatory diseases.

PMID- 29378166
TI  - Duplex recombinase polymerase amplification assays incorporating competitive
      internal controls for bacterial meningitis detection.
AB  - Recombinase polymerase amplification (RPA) is an isothermal nucleic acid
      amplification technology that provides rapid and robust infectious disease
      pathogen detection, ideal for point-of-care (POC) diagnostics in disease
      prevalent low-resource countries. We have developed and evaluated three duplex
      RPA assays incorporating competitive internal controls for the detection of
      leading bacterial meningitis pathogens. Streptococcus pneumoniae, Neisseria
      meningitidis and Haemophilus influenzae singleplex RPA assays were initially
      developed and evaluated, demonstrating 100% specificity with limits of detection
      of 4.1, 8.5 and 3.9 genome copies per reaction, respectively. Each assay was
      further developed into internally controlled duplex RPA assays via the
      incorporation of internal amplification control templates. Clinical performance
      of each internally controlled duplex RPA assay was evaluated by testing 64
      archived PCR-positive clinical samples. Compared to real-time PCR, all duplex RPA
      assays demonstrated 100% diagnostic specificity, with diagnostic sensitivities of
      100%, 86.3% and 100% for the S. pneumoniae, N. meningitidis and H. influenzae
      assays, respectively. This study details the first report of internally
      controlled duplex RPA assays for the detection of bacterial meningitis pathogens:
      S. pneumoniae, N. meningitidis and H. influenzae. We have successfully
      demonstrated the clinical diagnostic utility of each duplex RPA assay,
      introducing effective diagnostic technology for POC bacterial meningitis
      identification in disease-prevalent developing countries.

PMID- 29378167
TI  - Rapid detection of potyviruses from crude plant extracts.
AB  - Potyviruses (genus Potyvirus; family Potyviridae) are widely distributed and
      represent one of the most economically important genera of plant viruses.
      Therefore, their accurate detection is a key factor in developing efficient
      control strategies. However, this can sometimes be problematic particularly in
      plant species containing high amounts of polysaccharides and polyphenols such as
      yam (Dioscorea spp.). Here, we report the development of a reliable, rapid and
      cost-effective detection method for the two most important potyviruses infecting
      yam based on reverse transcription-recombinase polymerase amplification (RT-RPA).
      The developed method, named 'Direct RT-RPA', detects each target virus directly
      from plant leaf extracts prepared with a simple and inexpensive extraction method
      avoiding laborious extraction of high-quality RNA. Direct RT-RPA enables the
      detection of virus-positive samples in under 30 min at a single low operation
      temperature (37  degrees C) without the need for any expensive instrumentation.
      The Direct RT-RPA tests constitute robust, accurate, sensitive and quick methods
      for detection of potyviruses from recalcitrant plant species. The minimal sample
      preparation requirements and the possibility of storing RPA reagents without cold
      chain storage, allow Direct RT-RPA to be adopted in minimally equipped
      laboratories and with potential use in plant clinic laboratories and seed
      certification facilities worldwide.

PMID- 29378168
TI  - Potential of anti-inflammatory agents for treatment of atherosclerosis.
AB  - Chronic inflammation is a central pathogenic mechanism of atherosclerosis
      induction and progression. Vascular inflammation is associated with accelerated
      onset of late atherosclerosis complications. Atherosclerosis-related inflammation
      is mediated by a complex cocktail of pro-inflammatory cytokines, chemokines,
      bioactive lipids, and adhesion molecules, and blocking the key pro-atherogenic
      inflammatory mechanisms can be beneficial for treatment of atherosclerosis.
      Therapeutic agents that specifically target some of the atherosclerosis-related
      inflammatory mechanisms have been evaluated in preclinical and clinical studies.
      The most promising anti-inflammatory compounds for treatment of atherosclerosis
      include non-specific anti-inflammatory drugs, phospholipase inhibitors, blockers
      of major inflammatory cytokines, leukotrienes, adhesion molecules, and pro
      inflammatory signaling pathways, such as CCL2-CCR2 axis or p38 MAPK pathway.
      Ongoing studies attempt evaluating therapeutic utility of these anti-inflammatory
      drugs for treatment of atherosclerosis. The obtained results are important for
      our understanding of atherosclerosis-related inflammatory mechanisms and for
      designing randomized controlled studies assessing the effect of specific anti
      inflammatory strategies on cardiovascular outcomes.

PMID- 29378169
TI  - Aberrant endoplasmic reticulum stress mediates coronary artery spasm through
      regulating MLCK/MLC2 pathway.
AB  - Coronary artery spasm (CAS) is a pathophysiological phenomenon that may cause
      myocardial infarction and lead to circulatory collapse and death. Aberrant
      endoplasmic reticulum (ER) stress causes accumulation of misfolding proteins and
      has been reported to be involved in a variety of vascular diseases. The present
      study investigated the role of ER stress in the development of CAS and explored
      the possible molecular mechanisms. Initially, it was found that ER stress markers
      were elevated in response to drug-induced vascular smooth muscle cells (VSMCs)
      contraction. Pharmacologic activation of ER stress using Tunicamycin (Tm)
      persistently induced CAS and significantly promoted Pituitrin-induced CAS in mice
      as well as in a collagen gel contraction assay. On the contrary, pharmacologic
      inhibition of ER stress using 4-phenylacetic acid (4-PBA) completely blunted
      Pituitrin-induced CAS development in mice. Moreover, during the drug-induced
      VSMCs contraction, expression of ER stress markers were increased in parallel to
      those of myosin light chain kinase (MLCK) and phosphor-MLC2 (p-MLC2, at Ser19).
      After inhibiting MLCK activity by using its specific inhibitor ML-7, the ER
      stress activator Tm failed to activate the MLCK/MLC2 pathway and could neither
      trigger CAS in mice nor induce VSMCs contraction in vitro. Our results suggested
      that aberrant ER stress mediated CAS via regulating the MLCK/MLC2 pathway. ER
      stress activators might be more robust than the common drugs (Pituitrin or
      acetylcholine) as to induce vasocontraction and thus may serve as potential
      therapeutics against chronic bleeding, while its inhibitor might be useful for
      treatment of severe CAS caused by other medication.

PMID- 29378170
TI  - Long non-coding RNA PCAT-1 in human cancers: A meta-analysis.
AB  - BACKGROUND AND AIMS: Prostate cancer-associated non-coding RNA transcript-1(PCAT
      1), which is a newly discovered long non-coding RNA, is up-regulated in various
      cancers. We conducted a meta-analysis to assess the clinicopathological and
      prognostic value of PCAT-1 in patients with malignant tumors. METHODS: A
      systematic literature search involved PubMed, Medline, Cochrane Library, Web of
      Science, EMBASE database, Ovid, Chinese CNKI, and the Chinese WanFang database.
      The role of PCAT-1 in cancers was evaluated by pooled odds ratios (ORs) and
      hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 1005
      patients from nine studies were included in this meta-analysis. High expression
      of PCAT-1 was associated with depth of infiltration, lymph node metastasis,
      distant metastasis and TNM stage. However, increased PCAT-1 expression was not
      related to gender, tumor size and differentiation. Moreover, high PCAT-1
      expression was associated with poor overall survival (OS) and disease-free
      survival (DFS), and the pooled results suggested that PCAT-1 expression can be an
      independent predictive factor for overall survival. CONCLUSION: This meta
      analysis provides evidence that PCAT-1 expression is closely correlated with
      depth of infiltration, lymph node metastasis, distant metastasis and TNM stage,
      and that increased PCAT-1 expression may be a potential prognostic biomarker in
      human cancers. However, more large-scale studies are warranted.

PMID- 29378171
TI  - Discriminating myelodysplastic syndrome and other myeloid malignancies from non
      clonal disorders by multiparametric analysis of automated cell data.
AB  - BACKGROUND: We investigated the usefulness of novel complete blood count (CBC)
      data for discriminating myeloid malignancies from non-clonal CBC abnormalities.
      METHODS: Data were obtained during routine CBC tests of 119 samples from 37
      myelodysplastic syndrome (MDS) patients, 92 samples from 45 myeloproliferative
      neoplasm (MPN) patients, and 15 samples from 11 chronic myelogenous leukemia
      (CML) patients using a DxH800 (Beckman Coulter). Data obtained from patients with
      hypocellular bone marrow and from those with other non-clonal diseases with CBC
      abnormalities were included in the comparisons. RESULTS: For cell population data
      of neutrophils, the means of median, upper median, lower median, and low angle
      light scatters were significantly lower in MDS patients than in patients without
      hematological malignancies. Low hemoglobin density (LHD) did not significantly
      differ between the MDS and non-clonal cytopenia patients, but it was
      significantly higher in the MPN and CML patients. We selected 13 parameters and
      scored the MDS diagnosis using cut-off values obtained from receiver operating
      characteristic (ROC) curve analysis. Using a score > 9, MDS was distinguished
      from non-clonal cytopenia with a sensitivity of 92.4% and a specificity of 85.4%.
      CONCLUSIONS: Multiparametric analyses of new automated parameters are useful for
      discriminating MDS from non-clonal cytopenia.

PMID- 29378172
TI  - Modeling Idiopathic Pulmonary Fibrosis in Humanized Severe Combined
      Immunodeficient Mice.
AB  - Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease of unknown
      etiopathogenesis with limited therapeutic options. IPF is characterized by an
      abundance of fibroblasts and loss of epithelial progenitors, which cumulates in
      unrelenting fibrotic lung remodeling and loss of normal oxygenation. IPF has been
      challenging to model in rodents; nonetheless, mouse models of lung fibrosis
      provide clues as to the natural progression of lung injury and remodeling, but
      many have not been useful in predicting efficacy of therapeutics in clinical IPF.
      We provide a detailed methodologic description of various iterations of humanized
      mouse models, initiated by the i.v. injection of cells from IPF lung biopsy or
      explants specimens into severe combined immunodeficiency (SCID)/beige or nonobese
      diabetic SCID gamma mice. Unlike cells from normal lung samples, IPF cells
      promote persistent, nonresolving lung remodeling in SCID mice. Finally, we
      provide examples and discuss potential advantages and pitfalls of human-specific
      targeting approaches in a humanized SCID model of pulmonary fibrosis.

PMID- 29378173
TI  - Comparative Histopathologic Lesions of the Male Reproductive Tract during Acute
      Infection of Zika Virus in AG129 and Ifnar-/- Mice.
AB  - An understanding of the pathogenesis of infection with the Zika virus in the male
      reproductive tract is vital for the development of vaccines and antivirals that
      will limit or prevent sexual transmission. Two common immunocompromised mouse
      strains used in transmission studies-male with genes encoding interferon types I
      and II receptor gene knockout (IFNAR/IFNGR; AG129) and with interferon type 1
      receptor knockout (Ifnar-/-) were infected with a Puerto Rican Zika virus isolate
      (PRVABC59), and pathology was assessed 5 to 11 days after infection. Virus was
      detected by immunohistochemistry and quantitative RT-PCR in the testicle and
      epididymis of AG129 and Ifnar-/- mice, and by immunohistochemistry in the
      prostate and seminal vesicle of infected AG129 mice. Severe disease
      manifestations initiating as epididymitis and progressing to orchitis were
      observed in both models, with more severe inflammation noted in the AG129 mouse
      strain. Significant inflammation was not observed in any evaluated accessory sex
      gland at any point during infection. Time-course analysis of infection revealed
      an increase in the severity of disease within the epididymis of both strains,
      indicating a potential route of sexual transmission. Male mice with Ifnar-/- may
      better recapitulate Zika virus in humans and provide insight into the mechanism
      of sexual transmission, due to milder histopathologic lesions, the presence of
      histologically normal sperm in epididymal tubules, and an ability to survive the
      acute phase of disease.

PMID- 29378175
TI  - Re: African Americans in Oral and Maxillofacial Surgery: Factors Affecting Career
      Choice, Satisfaction and Practice Patterns.

PMID- 29378176
TI  - Total Maxillary Alveolar Osteotomy: Surgical Technique and Review of Its
      Efficacy.
AB  - PURPOSE: The total maxillary alveolar osteotomy (TMxAO) is not commonly used to
      manage maxillary skeletal deformities. This article describes the technique,
      reviews its stability, and discusses its advantages over the more popular Le Fort
      I osteotomy. MATERIALS AND METHODS: A series of 177 TMxAO patients satisfying the
      inclusion criteria from a cadre of 234 patients undergoing TMxAO between 1985 and
      1993 were evaluated in a retrospective cohort study regarding achievement of
      predicted anatomic movements, stability of skeletal results, and preservation of
      inter-alar dimension. The patients were evaluated early postoperatively and at 11
      to 14 months postoperatively, and the data were exposed to the Shapiro-Wilk test
      and analysis of variance and analyzed using SPSS software (version 21; IBM,
      Armonk, NY) at the 99% level of confidence (P <= .01). RESULTS: Only in 58% of
      patients did the designed millimetric study model changes correspond precisely to
      the millimetric changes disclosed in a comparison of preoperative and early
      postoperative cephalograms. Comparison of early and late postoperative
      cephalograms, with infrequent exceptions, described millimetric instabilities of
      less than 2 mm and angular instabilities of less than 2 degrees . Despite 2
      significant outliers, the average inter-alar instability as determined by direct
      measurement was 0.19 mm. CONCLUSIONS: This study suggests that the TMxAO compares
      favorably in stability with the Le Fort I osteotomy as recorded in the literature
      and, in terms of versatility, mobility of segments, avoidance of anatomic hazard,
      and preservation of nasal width, offers advantages in comparison.

PMID- 29378174
TI  - Hippo Cascade Controls Lineage Commitment of Liver Tumors in Mice and Humans.
AB  - Primary liver cancer consists mainly of hepatocellular carcinoma (HCC) and
      intrahepatic cholangiocarcinoma (ICC). A subset of human HCCs expresses a ICC
      like gene signature and is classified as ICC-like HCC. The Hippo pathway is a
      critical regulator of normal and malignant liver development. However, the
      precise function(s) of the Hippo cascade along liver carcinogenesis remain to be
      fully delineated. The role of the Hippo pathway in a murine mixed HCC/ICC model
      induced by activated forms of AKT and Ras oncogenes (AKT/Ras) was investigated.
      The authors demonstrated the inactivation of Hippo in AKT/Ras liver tumors
      leading to nuclear localization of Yap and TAZ. Coexpression of AKT/Ras with
      Lats2, which activates Hippo, or the dominant negative form of TEAD2 (dnTEAD2),
      which blocks Yap/TAZ activity, resulted in delayed hepatocarcinogenesis and
      elimination of ICC-like lesions in the liver. Mechanistically, Notch2 expression
      was found to be down-regulated by the Hippo pathway in liver tumors.
      Overexpression of Lats2 or dnTEAD2 in human HCC cell lines inhibited their growth
      and led to the decreased expression of ICC-like markers, as well as Notch2
      expression. Altogether, this study supports the key role of the Hippo cascade in
      regulating the differentiation status of liver tumors.

PMID- 29378177
TI  - Leadership in Ophthalmology: The Role of Physician-MBAs.
AB  - PURPOSE: As American health care evolves, an increasing number of doctors are
      pursuing MBAs. However, relatively little is known about how business training
      translates into their future careers. This study characterizes ophthalmologists
      who have completed MBAs and identifies opportunities for physician leadership in
      the field. DESIGN: Cross-sectional study. METHODS: We identified 120
      ophthalmologists who hold MBAs. We searched each individual's online profiles to
      collect information on demographics, training, and professional activities.
      RESULTS: Physician-MBAs in ophthalmology are 80% male; 80% are fellowship
      trained; and 28% are in primarily nonclinical roles and 55% participate in
      significant nonclinical activity. Hospital administration is most common (31%),
      followed by pharmaceutical administration (7%) and consulting (5%). Older
      ophthalmologist-MBAs were more likely to work in nonclinical roles, with 79% of
      those who completed residency before 2000 engaged in significant nonclinical
      activity compared to 30% of those who completed residency after 2000. The most
      common employers of physician-MBAs in ophthalmology are academic medical centers
      (43%), large group practices (30%), and private practices (13%). CONCLUSIONS: The
      majority of ophthalmologist-MBAs work in primarily clinical roles, although a
      sizable proportion hold nonclinical positions. Moving forward, we anticipate an
      increased role for physician leaders in health care administration, policy, and
      entrepreneurship. While formal management training is not necessary for these
      roles, a growing number of physicians have sought out MBAs to support their
      nonclinical interests.

PMID- 29378178
TI  - Limbal Stem Cell Deficiency-Demography and Underlying Causes.
AB  - PURPOSE: To determine the demographic features of patients affected by limbal
      stem cell deficiency (LSCD), and to identify the underlying causes of LSCD.
      DESIGN: Retrospective, multicenter case series. SETTING: Two large tertiary care
      ophthalmology hospitals. SUBJECTS: Patients with a diagnosis of LSCD presenting
      from January 1, 2005 to December 31, 2014. METHODS: Records of patients with a
      clinical diagnosis of LSCD were reviewed. Demographic details and clinical
      features at presentation, as well as the underlying cause of LSCD (if
      identified), were noted. Descriptive statistical analysis and chart preparation
      were done. Main outcome measures were type of LSCD (unilateral or bilateral), age
      and sex of patients, extent of LSCD (clock hours of limbus involved), and
      underlying cause of LSCD. RESULTS: We found 1331 patients with LSCD in the 10
      year period under study. Unilateral LSCD was more common (791 patients) than
      bilateral LSCD (540 patients). Out of 1331 patients, 875 (65.74%) were male. The
      median age of patients was 24 years. Extent of LSCD could be determined in 1849
      eyes, of which 1239 eyes (67.00%) had total LSCD. The underlying cause of LSCD
      could be identified in 1512 eyes. In cases of unilateral LSCD, ocular surface
      burns was the commonest identifiable cause (83.73%). The leading identifiable
      causes of bilateral LSCD were ocular surface burns (29.95%), allergic
      conjunctivitis (29.48%), Stevens-Johnson syndrome (SJS) or toxic epidermal
      necrolysis (TEN) (23.11%), aniridia (9.43%), and mucous membrane pemphigoid
      (3.54%). Lime ("chuna") injury was responsible for ocular surface burns in 352
      out of 567 cases in which the agent was identified (62.08%). CONCLUSIONS: In our
      study, unilateral LSCD was more common than bilateral LSCD. Young male subjects
      were commonly affected, with a majority of eyes suffering from total LSCD.
      Overall, ocular surface burns are the leading cause of LSCD. Unilateral and
      bilateral LSCD had a markedly different distribution of causes, necessitating
      different approaches to management.

PMID- 29378179
TI  - Human GIP(3-30)NH2 inhibits G protein-dependent as well as G protein-independent
      signaling and is selective for the GIP receptor with high-affinity binding to
      primate but not rodent GIP receptors.
AB  - GIP(3-30)NH2 is a high affinity antagonist of the GIP receptor (GIPR) in humans
      inhibiting insulin secretion via G protein-dependent pathways. However, its
      ability to inhibit G protein-independent signaling is unknown. Here we determine
      its action on arrestin-recruitment and receptor internalization in recombinant
      cells. As GIP is adipogenic, we evaluate the inhibitory actions of GIP(3-30)NH2
      in human adipocytes. Finally, we determine the receptor selectivity of GIP(3
      30)NH2 among other human and animal GPCRs. cAMP accumulation and beta-arrestin 1
      and 2 recruitment were studied in transiently transfected HEK293 cells and real
      time internalization in transiently transfected HEK293A and in HEK293A beta
      arrestin 1 and 2 knockout cells. Furthermore, human subcutaneous adipocytes were
      assessed for cAMP accumulation following ligand stimulation. Competition binding
      was examined in transiently transfected COS-7 cells using human 125I-GIP(3
      30)NH2. The selectivity of human GIP(3-30)NH2 was examined by testing for
      agonistic and antagonistic properties on 62 human GPCRs. Human GIP(3-30)NH2
      inhibited GIP(1-42)-induced cAMP and beta-arrestin 1 and 2 recruitment on the
      human GIPR and Schild plot analysis showed competitive antagonism with a pA2 and
      Hill slope of 16.8 nM and 1.11 +/- 0.02 in cAMP, 10.6 nM and 1.15 +/- 0.05 in
      beta-arrestin 1 recruitment, and 10.2 nM and 1.06 +/- 0.05 in beta-arrestin 2
      recruitment. Efficient internalization of the GIPR was dependent on the presence
      of either beta-arrestin 1 or 2. Moreover, GIP(3-30)NH2 inhibited GIP(1-42)
      induced internalization in a concentration-dependent manner and notably also
      inhibited GIP-mediated signaling in human subcutaneous adipocytes. Finally, the
      antagonist was established as GIPR selective among 62 human GPCRs being species
      specific with high affinity binding to the human and non-human primate (Macaca
      fascicularis) GIPRs, and low affinity binding to the rat and mouse GIPRs (Kd
      values of 2.0, 2.5, 31.6 and 100 nM, respectively). In conclusion, human GIP(3
      30)NH2 is a selective and species-specific GIPR antagonist with broad inhibition
      of signaling and internalization in transfected cells as well as in human
      adipocytes.

PMID- 29378180
TI  - Regulation of Kv4.3 and hERG potassium channels by KChIP2 isoforms and DPP6 and
      response to the dual K+ channel activator NS3623.
AB  - Transient outward potassium current (Ito) contributes to early repolarization of
      many mammalian cardiac action potentials, including human, whilst the rapid
      delayed rectifier K+ current (IKr) contributes to later repolarization. Fast Ito
      channels can be produced from the Shal family KCNDE gene product Kv4.3s, although
      accessory subunits including KChIP2.x and DPP6 are also needed to produce a near
      physiological Ito. In this study, the effect of KChIP2.1 & KChIP2.2 (also known
      as KChIP2b and KChIP2c respectively), alone or in conjunction with the accessory
      subunit DPP6, on both Kv4.3 and hERG were evaluated. A dual Ito and IKr
      activator, NS3623, has been recently proposed to be beneficial in heart failure
      and the action of NS3623 on the two channels was also investigated. Whole-cell
      patch-clamp experiments were performed at 33 +/- 1  degrees C on HEK293 cells
      expressing Kv4.3 or hERG in the absence or presence of these accessory subunits.
      Kv4.3 current magnitude was augmented by co-expression with either KChIP2.2 or
      KChIP2.1 and KChIP2/DPP6 with KChIP2.1 producing a greater effect than KChIP2.2.
      Adding DPP6 removed the difference in Kv4.3 augmentation between KChIP2.1 and
      KChIP2.2. The inactivation rate and recovery from inactivation were also altered
      by KChIP2 isoform co-expression. In contrast, hERG (Kv11.1) current was not
      altered by co-expression with KChIP2.1, KChIP2.2 or DPP6. NS3623 increased Kv4.3
      amplitude to a similar extent with and without accessory subunit co-expression,
      however KChIP2 isoforms modulated the compound's effect on inactivation time
      course. The agonist effect of NS3623 on hERG channels was not affected by
      KChIP2.1, KChIP2.2 or DPP6 co-expression.

PMID- 29378181
TI  - The E3 ubiquitin ligases HOIP and cIAP1 are recruited to the TNFR2 signaling
      complex and mediate TNFR2-induced canonical NF-kappaB signaling.
AB  - Tumor Necrosis Factor (TNF) is a proinflammatory cytokine that elicits its action
      by binding to two cell surface TNF receptors (TNFR), TNFR1 and TNFR2, which are
      expressed by many different cell types. Stimulation of TNFR1 activates canonical
      NF-kappaB signaling, leading to the NF-kappaB dependent expression of a large
      number of genes. Canonical NF-kappaB signaling requires the assembly of a TNFR1
      signaling complex at the cell membrane, whose formation is regulated by different
      protein ubiquitination events. In this context, recruitment of the Linear
      Ubiquitin Chain Assembly Complex (LUBAC) to TNFR1 plays an important role by
      mediating M1-linked polyubiquitination of specific NF-kappaB signaling proteins.
      In contrast to TNFR1, much less is known about the role of ubiquitination in
      TNFR2 signaling. Here we demonstrate that specific TNFR2 stimulation rapidly
      triggers M1- and K63-linked polyubiquitination at the TNFR2 signaling complex. In
      agreement, TNFR2 stimulation induces the recruitment of HOIP, a LUBAC component
      and the only known E3 ubiquitin ligase for M1-polyubiquitination, to the TNFR2
      signaling complex. Also cIAP1, a E3 ubiquitin ligase able to modify proteins with
      K63-polyubiquitin chains, was recruited to the TNFR2 signaling complex. Treatment
      of cells with a cIAP antagonist inhibited the recruitment of HOIP and prevented
      HOIP-mediated M1-ubiquitination of the TNFR2 signaling complex, indicating that
      HOIP recruitment to the TNFR2 relies on cIAPs. Finally, we show that both HOIP
      and cIAP1 are required for TNFR2-induced canonical NF-kappaB activation.
      Together, our findings demonstrate an important role for M1- and K63-linked
      polyubiquitination in TNFR2 signaling.

PMID- 29378182
TI  - Activation of mitochondrial fusion provides a new treatment for mitochondria
      related diseases.
AB  - Mitochondria fragmentation destabilizes mitochondrial membranes, promotes
      oxidative stress and facilitates cell death, thereby contributing to the
      development and the progression of several mitochondria-related diseases.
      Accordingly, compounds that reverse mitochondrial fragmentation could have
      therapeutic potential in treating such diseases. BGP-15, a hydroxylamine
      derivative, prevents insulin resistance in humans and protects against several
      oxidative stress-related diseases in animal models. Here we show that BGP-15
      promotes mitochondrial fusion by activating optic atrophy 1 (OPA1), a GTPase
      dynamin protein that assist fusion of the inner mitochondrial membranes.
      Suppression of Mfn1, Mfn2 or OPA1 prevents BGP-15-induced mitochondrial fusion.
      BGP-15 activates Akt, S6K, mTOR, ERK1/2 and AS160, and reduces JNK
      phosphorylation which can contribute to its protective effects. Furthermore, BGP
      15 protects lung structure, activates mitochondrial fusion, and stabilizes
      cristae membranes in vivo determined by electron microscopy in a model of
      pulmonary arterial hypertension. These data provide the first evidence that a
      drug promoting mitochondrial fusion in in vitro and in vivo systems can reduce or
      prevent the progression of mitochondria-related disorders.

PMID- 29378183
TI  - CBFA2T2 is required for BMP-2-induced osteogenic differentiation of mesenchymal
      stem cells.
AB  - Bone morphogenetic protein (BMP) signaling is one of the essential pathways
      involved in osteogenic differentiation of mesenchymal stem cells (MSCs) and
      regulation of bone formation. While BMP-2 has been approved for clinic use, the
      underlying mechanisms remain not fully understood. In this study, we found co
      repressor CBFA2T2 (core-binding factor, runt domain, alpha subunit 2,
      translocated to, 2) expression was significantly upregulated in response to BMP-2
      treatment during osteogenic differentiation of human dental pulp stem cells
      (hDPSCs) and mouse bone marrow stromal cells (mBMSCs). siRNA-mediated knockdown
      of CBFA2T2 blunted the BMP-2-induced allkaline phosphatase (ALP) activity,
      mineralization of extracelluar matrix (ECM), and expression of osteogenic related
      genes in both hDPSCs and mBMSCs. Mechanistically, knockdown of CBFA2T2 promoted
      expression of euchromatic histone methyltransferase 1 (EHMT1) in mBMSCs, which
      further led to upregulation of H3K9me2 levels at promoter of runt related
      transcription factor 2 (Runx2), the master regulator of osteogenesis.
      Collectively, our findings indicate that CBFA2T2 is required for BMP-2-induced
      osteogenic differentiation of MSCs through inhibition of EHMT1-mediated histone
      methylation at Runx2 promoter.

PMID- 29378184
TI  - miR-218 and miR-129 regulate breast cancer progression by targeting Lamins.
AB  - Breast cancer is the most frequently diagnosed life-threatening cancer in women.
      Triple-negative breast cancer (TNBC) has an aggressive clinical behavior, but the
      treatment of TNBC remains challenging. MicroRNAs (miRNAs) have emerged as a
      potential target for the diagnosis, therapy and prognosis of breast cancer.
      However, the precise role of miRNAs and their targets in breast cancer remain to
      be elucidated. Here we show that miR-218 is downregulated and miR-129 is
      upregulated in TNBC samples and their expressions confer prognosis to patients.
      Gain-of-function and loss-of-function analysis reveals that miR-218 has a tumor
      suppressive activity, while miR-129 acts as an oncomir in breast cancer. Notably,
      miR-218 and miR-129 directly target Lamin B1 and Lamin A, respectively, which are
      also found to be deregulated in human breast tumors. Finally, we demonstrate
      Lamins as the major factors in reliable miR-218 and miR-129 functions for breast
      cancer progression. Our findings uncover a new miRNA-mediated regulatory network
      for different Lamins and provide a potential therapeutic target for breast
      cancer.

PMID- 29378185
TI  - Application of the SSB biosensor to study in vitro transcription.
AB  - Gene expression, catalysed by RNA polymerases (RNAP), is one of the most
      fundamental processes in living cells. The majority of methods to quantify mRNA
      are based upon purification of the nucleic acid which leads to experimental
      inaccuracies and loss of product, or use of high cost dyes and sensitive
      spectrophotometers. Here, we describe the use of a fluorescent biosensor based
      upon the single stranded binding (SSB) protein. In this study, the SSB biosensor
      showed similar binding properties to mRNA, to that of its native substrate,
      single-stranded DNA (ssDNA). We found the biosensor to be reproducible with no
      associated loss of product through purification, or the requirement for expensive
      dyes. Therefore, we propose that the SSB biosensor is a useful tool for
      comparative measurement of mRNA yield following in vitro transcription.

PMID- 29378186
TI  - Effect of ghrelin on the motor deficit caused by the ablation of nigrostriatal
      dopaminergic cells or the inhibition of striatal dopamine receptors.
AB  - Ghrelin plays roles in a wide range of central functions by activating the growth
      hormone secretagogue receptor (GHSR). This receptor has recently been found in
      the substantia nigra (SN) to control dopamine (DA)-related physiological
      functions. The dysregulation of DA neurons in the SN pars compacta (SNc) and the
      consequent depletion of striatal DA are known to underlie the motor deficits
      observed in Parkinson's disease (PD). In the present study, we further
      investigated the role of the SN-ghrelin system in motor function under the
      stereotaxic injection of AAV-CMV-FLEX-diphtheria toxin A (DTA) into the SN of
      dopamine transporter (DAT)-Cre (DATSN::DTA) mice to expunge DA neurons of the
      SNc. First, we confirmed the dominant expression of GHSR1a, which is a functional
      GHSR, in tyrosine hydroxylase (TH)-positive DA neurons in the SNc of control
      mice. In DATSN::DTA mice, we clearly observed motor dysfunction using several
      behavioral tests. An immunohistochemical study revealed a dramatic loss of TH
      positive DA neurons in the SNc and DAT-labeled axon terminals in the striatum,
      and an absence of mRNAs for TH and DAT in the SN of DATSN::DTA mice. The mRNA
      level of GHSR1a was drastically decreased in the SN of these mice. In normal
      mice, we also found the mRNA expression of GHSR1a within GABAergic neurons in the
      SN pars reticulata (SNr). Under these conditions, a single injection of ghrelin
      into the SN failed to improve the motor deficits caused by ablation of the
      nigrostriatal DA network using DATSN::DTA mice, whereas intra-SN injection of
      ghrelin suppressed the motor dysfunction caused by the administration of
      haloperidol, which is associated with the transient inhibition of DA
      transmission. These findings suggest that phasic activation of the SNc-ghrelin
      system could improve the dysregulation of nigrostriatal DA transmission related
      to the initial stage of PD, but not the motor deficits under the depletion of
      nigrostriatal DA. Although GHSRs are found in non-DA cells of the SNr, GHSRs on
      DA neurons in the SNc may play a crucial role in motor function.

PMID- 29378188
TI  - How brain response and eating habits modulate food energy estimation.
AB  - The estimates we do of the energy content of different foods tend to be
      inaccurate, depending on several factors. The elements influencing such
      evaluation are related to the differences in the portion size of the foods shown,
      their energy density (kcal/g), but also to individual differences of the
      estimators, such as their body-mass index (BMI) or eating habits. Within this
      context the contribution of brain regions involved in food-related decisions to
      the energy estimation process is still poorly understood. Here, normal-weight and
      overweight/obese women with restrained or non-restrained eating habits, received
      anodal transcranial direct current stimulation (AtDCS) to modulate the activity
      of the left dorsolateral prefrontal cortex (dlPFC) while they performed a food
      energy estimation task. Participants were asked to judge the energy content of
      food images, unaware that all foods, for the quantity presented, shared the same
      energy content. Results showed that food energy density was a reliable predictor
      of their energy content estimates, suggesting that participants relied on their
      knowledge about the food energy density as a proxy for estimating food energy
      content. The neuromodulation of the dlPFC interacted with individual differences
      in restrained eating, increasing the precision of the energy content estimates in
      participants with higher scores in the restrained eating scale. Our study
      highlights the importance of eating habits, such as restrained eating, in
      modulating the activity of the left dlPFC during food appraisal.

PMID- 29378187
TI  - Apolipoprotein A-IV enhances cholecystokinnin secretion.
AB  - Cholecystokinin (CCK) and apolipoprotein A-IV (ApoA-IV) are gastrointestinal
      peptides that play an important role in controlling energy homeostasis. Lymphatic
      ApoA-IV and plasma CCK secretion are mediated via a chylomicron formation
      dependent pathway during a dietary lipid infusion. Given their similar roles as
      satiating proteins, the present study examines how the two peptides interact in
      their function. Specifically, this study sought to understand how ApoA-IV
      regulates CCK secretion. For this purpose, Cck gene expression in the small
      intestines of ApoA-IV knockout (ApoA-IV-KO) and wild-type (WT) mice were compared
      under an array of feeding conditions. When fed with a chow or high-fat diet
      (HFD), basal levels of Cck transcripts were significantly reduced in the duodenum
      of ApoA-IV-KO mice compared to WT mice. Furthermore, after an oral gavage of a
      lipid mixture, Cck gene expression in the duodenum was significantly reduced in
      ApoA-IV-KO mice relative to the change seen in WT mice. To determine the
      mechanism by which ApoA-IV modulates Cck gene expression, STC-1 cells were
      transfected with predesigned mouse lysophosphatidic acid receptor 5 (LPAR5) small
      interfering RNA (siRNA) to knockdown Lpar5 gene expression. In this in-vitro
      study, mouse recombinant ApoA-IV protein increased Cck gene expression in
      enteroendocrine STC-1 cells and stimulated CCK release from the STC-1 cells.
      However, the levels of CCK protein and Cck expression were attenuated when Lpar5
      was knocked down in the STC-1 cells. Together these observations suggest that
      dietary lipid-induced ApoA-IV is associated with Cck synthesis in the duodenum
      and that ApoA-IV protein directly enhances CCK release through the activation of
      a LPAR5-dependent pathway.

PMID- 29378189
TI  - JN-2, a C-X-C motif chemokine receptor 3 antagonist, ameliorates arthritis
      progression in an animal model.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterized
      by uncontrolled joint inflammation and destruction of bone and cartilage.
      Previous studies have shown that C-X-C motif chemokine 10 (CXCL10) has important
      roles in RA development and that blocking CXCL10 expression effectively inhibits
      arthritis progression in animal models. However, clinical study using anti-CXCL10
      monoclonal antibody (MDX-1100) to block CXCL10 expression in patients with RA did
      not show significant effectiveness. Therefore, we turned our attention to C-X-C
      motif chemokine receptor 3 (CXCR3), which is a receptor for CXCL9, CXCL10, and
      CXCL11, to treat RA. In the present study, administration of JN-2, our newly
      developed CXCR3 antagonist, ameliorated the progression of arthritis in a
      collagen-induced arthritis animal model. JN-2 also inhibited CXCR3-induced cell
      migration and pro-inflammatory cytokine expression of bone marrow-derived
      macrophages and CD4+ T cells in vitro. In addition, we found that CXCL10 formed
      an auto-amplification loop through activation of NFkappaB. Furthermore,
      Phosphorylation of p65 at serine 536 played an important role in the auto
      amplification of CXCL10. Overall, the present results demonstrated that JN-2
      decreased inflammation by inhibiting CXCR3-enhanced cell migration and pro
      inflammatory cytokine expression, which then ameliorated arthritis progression.

PMID- 29378190
TI  - Metabotropic glutamate 7 receptor agonist AMN082 inhibits glutamate release in
      rat cerebral cortex nerve terminal.
AB  - AMN082 is a selective metabotropic glutamate mGlu7 receptor agonist reported to
      exhibit antidepressant activity. Considering that excessive glutamate release is
      involved in the pathogenesis of depression, the effect of N,N'-dibenzyhydryl
      ethane-1,2-diamine dihydrochloride (AMN082) on glutamate release in rat
      cerebrocortical nerve terminals and the possible underlying mechanism were
      investigated. In this study, we observed here that AMN082 inhibited 4
      aminopyridine-evoked glutamate release and this phenomenon was blocked by the
      metabotropic glutamate mGlu7 receptor antagonist MMPIP. Moreover, western blot
      analysis and immunocytochemistry confirmed the presence of presynaptic
      metabotropic glutamate mGlu7 receptor proteins. The effect of AMN082 on the 4
      aminopyridine-evoked release of glutamate was prevented by chelating the
      extracellular Ca2+ ions and the vesicular transporter inhibitor; however, the
      effect of AMN082 was unaffected by the glutamate transporter inhibitor. AMN082
      reduced the elevation of 4-aminopyridine-evoked intrasynaptosomal Ca2+
      concentration, but did not alter the synaptosomal membrane potential. In the
      presence of the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker, the
      adenylate cyclase inhibitor, and the protein kinase A inhibitor, the action of
      AMN082 on the 4-aminopyridine-evoked glutamate release was markedly reduced.
      These results suggest that the activation of the metabotropic glutamate mGlu7
      receptors by AMN082 reduces adenylate cyclase/protein kinase A activation, which
      subsequently reduces the entry of Ca2+ through voltage-dependent Ca2+ channels
      and decreases evoked glutamate release. Additionally, fluoxetine, a clinically
      effective antidepressant, completely occluded the inhibitory effect of AMN082 on
      glutamate release, thus indicating the existence of a common intracellular
      mechanism for these two compounds to inhibit glutamate release from the
      cerebrocortical nerve terminals.

PMID- 29378191
TI  - Involvement of the N/OFQ-NOP system in rat morphine antinociceptive tolerance:
      Are astrocytes the crossroad?
AB  - The development of tolerance to the antinociceptive effect is a main problem
      associated with the repeated administration of opioids. The progressively higher
      doses required to relieve pain reduce safety and exacerbate the side effects of
      classical opioid receptor agonists like morphine. Nociceptin/orphanin FQ (N/OFQ)
      and its NOP receptor constitute the fourth endogenous opioid system that is
      involved in the control of broad spectrum of biological functions, including pain
      transmission. Aim of this work was to evaluate the relevance of the N/OFQ-NOP
      system in morphine antinociceptive action and in the development of morphine
      tolerance in the rat. Continuous spinal intrathecal infusion of morphine (1-3
      nmol/h) evoked analgesic effects for 5 days in wild type animals. The same doses
      infused in NOP(-/-) rats showed a lower analgesic efficacy, while the onset of
      tolerance was delayed to day 9. N/OFQ (1-3 nmol/h), continuously infused in
      NOP(+/+) animals, showed an analgesic profile similar to morphine.
      Immunohistochemical analysis of the dorsal horn of the spinal cord of morphine
      tolerant NOP(+/+) rats showed an increased number of Iba1- and GFAP-positive
      cells (microglia and astrocytes, respectively). Interestingly, microglia but not
      astrocyte activation was observed in NOP(-/-) morphine tolerant rat. A selective
      activation of astrocytes was observed in the dorsal horn of wild type N/OFQ
      tolerant rats. The antinociceptive effect of morphine partially depends by the
      N/OFQ-NOP system that participates in the development of morphine tolerance. In
      particular, NOP receptors are involved in morphine-induced astrocyte activation,
      and N/OFQ per se increases astrocyte density.

PMID- 29378192
TI  - Berberine attenuates podocytes injury caused by exosomes derived from high
      glucose-induced mesangial cells through TGFbeta1-PI3K/AKT pathway.
AB  - Diabetic nephropathy is the most common microvascular complications of diabetes.
      Berberine is the main active ingredient of Coptis chinensis and previous studies
      have been showed that berberine could delay the progression of diabetic
      nephropathy by regulating related cytokines and signaling pathways. Glomerular
      mesangial cells and podocytes are two vital indigenous cells of kidney and
      interaction between these two cellular components via exosomes might affect
      function of glomerulus in diabetic nephropathy condition. On the basis of our
      previous studies, transwell systems were used to demonstrate that the exosomes
      released by glomerular mesangial cells induced by the high glucose were involved
      in podocytes injury. The current study demonstrates that berberine can reduce
      TGFbeta1 in exosomes released by high glucose-induced glomerular mesangial cells.
      Berberine-treated high glucose-induced exosomes which are secreted by glomerular
      mesangial cells can protect damage of podocytes by reducing apoptosis and
      increasing adhesion. These results suggest that berberine could protect the
      function of podocytes through inhibiting the transfer of TGFbeta1 from the
      glomerular mesangial cells to the podocytes, which is one of the potential
      mechanisms of protective effect of berberine on diabetic nephropathy.

PMID- 29378193
TI  - PPARgamma agonists sensitize PTEN-deficient resistant lung cancer cells to EGFR
      tyrosine kinase inhibitors by inducing autophagy.
AB  - We aimed to develop novel drug combination strategy to overcome drug resistance
      to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in the
      treatment of non-small cell lung cancer (NSCLC). Peroxisome proliferator
      activated receptor gamma (PPARgamma) is a nuclear receptor, which upon activation
      upregulates phosphatase and tensin homolog (PTEN) to inhibit cell signaling
      downstream of PI3K to mediate apoptosis. To this end, PTEN loss is a known
      mechanism contributing to resistance to EGFR TKIs. Therefore, PPARgamma agonists
      are hypothesized to overcome EGFR TKI resistance. Using human NSCLC cell models
      with PTEN deficiency, the potentiation of EGFR TKI anticancer activity by
      PPARgamma agonists was evaluated. PPARgamma agonists were found to upregulate
      PTEN, subsequently inhibiting the PI3K-Akt signaling pathway, and thus enhancing
      the anticancer activity of gefitinib (a first generation EGFR TKI). Chemical and
      genetic inhibition of PPARgamma were shown to prevent this potentiation of
      anticancer activity by PPARgamma agonists, thus confirming the crucial role
      played by PPARgamma activation. Interestingly, the tested PPARgamma agonists were
      also found to induce autophagy, as evidenced by the increased expression of an
      autophagy marker LC3-II and the autophagic degradation of p62/SQSTM1. PPARgamma
      agonists-induced autophagic cell death was believed to contribute to the
      circumvention of resistance in PTEN-deficient cells because the genetic silencing
      of ATG5 (an autophagy mediator) was found to eliminate the drug potentiation
      effect by the PPARgamma agonists. Our findings thus provide the basis for the
      rational and personalized use of PPARgamma agonists in combination with EGFR TKIs
      in lung cancer patients.

PMID- 29378194
TI  - NaHS prejunctionally inhibits the cardioaccelerator sympathetic outflow in pithed
      rats.
AB  - Hydrogen sulfide is a gasotransmitter that mediates cardiovascular responses and
      could protect the heart from ischemia-reperfusion damage. Furthermore, this gas
      mediates bradycardia although the mechanisms involved remain elusive. In this
      regard, the inhibition of the cardiac sympathetic outflow may be partially
      involved. Thus, this study was designed to determine the capability of NaHS to
      inhibit the tachycardic responses induced by preganglionic stimulation of the
      cardioaccelerator sympathetic outflow. Wistar rats were anaesthetized with
      isoflurane, cannulated and pithed. Then, animals received gallamine and the
      effect of i.v. infusion of NaHS (310 and 560 MUg/kg min) was evaluated on the
      tachycardic responses induced by (1) sympathetic stimulation (0.1-3.2 Hz) at C7
      T1 region of the vertebral column; or i.v. injections of (2) noradrenaline (0.03
      3 MUg/kg) and (3) isoproterenol (0.0003-0.1 MUg/kg). Notably, NaHS significantly
      and dose-dependently inhibited the tachycardic responses induced by electrical
      stimulation of the preganglionic sympathetic outflow without significantly modify
      the tachycardic responses induced by either noradrenaline or isoproterenol. These
      results allow us to conclude that i.v. infusion of NaHS inhibited the tachycardic
      responses induced by stimulation of the cardioaccelerator sympathetic outflow by
      a prejunctional mechanism.

PMID- 29378196
TI  - Additive effect of simultaneous continuous administration of degarelix and TAK
      448 on LH suppression in a castrated rat model.
AB  - Gonadotropin releasing hormone (GnRH) analogs have long been used in androgen
      deprivation therapy (ADT) in the treatment of prostate cancer. Chronic
      administration of either GnRH agonists or antagonists leads to suppression of
      testosterone production in the testes via either downregulation or direct
      blockade of the GnRH receptor in the pituitary, respectively. Chronic
      administration of kisspeptin analogs has more recently been shown to lead to
      testosterone suppression via desensitization of GnRH neurons in the hypothalamus
      and an optimized kisspeptin analog, TAK-448, was proven effective in a small
      phase 1 trial. The current study explored the hypothesis that co-administration
      of TAK-448 and the GnRH antagonist, degarelix, would have an additive effect on
      hormonal suppression, as a result of simultaneous intervention in separate steps
      in the same pathway. TAK-448 or degarelix were first administered individually to
      castrated rats in order to identify low doses capable of partial or no
      suppression of luteinizing hormone (LH). In the second step, combinations of the
      low doses of TAK-448 and degarelix were assessed in a 14 day study and compared
      to the drugs administered separately. The results showed that simultaneous
      intervention at the kisspeptin and GnRH receptors caused a more pronounced LH
      suppression than either drug alone, demonstrating an additive or potentiating
      effect. These results suggest that such a drug combination may hold promise as
      novel forms of androgen deprivation therapy in the treatment of prostate cancer.

PMID- 29378195
TI  - Inhibition of hepatic apolipoprotein A-I gene expression by histamine.
AB  - In a recent high throughput analysis to identify drugs that alter hepatic
      apolipoprotein A-I (apo A-I) expression, histamine receptor one (H1) antagonists
      emerged as potential apo A-1 inducing drugs. Thus the present study was
      undertaken to identify some of the underlying molecular mechanisms of the effect
      of antihistaminic drugs on apo AI production. Apo A-I levels were measured by
      enzyme immunoassay and Western blots. Apo A-I mRNA levels were measured by
      reverse transcription real-time PCR using glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) mRNA as the internal control. The effects of histamine and
      antihistamines on apo A-I gene were determined by transient transfection of
      plasmids containing the apo A-I gene promoter. Histamine repressed while (H1)
      receptor antagonist azelastine increased apo A-I protein and mRNA levels within
      48 h in a dose-dependent manner. Azelastine and histamine increased and
      suppressed, respectively, apo A-I gene promoter activity through a peroxisome
      proliferator activated receptor alpha response element. Treatment of HepG2 cells
      with other H1 receptor antagonists including fexofenadine, cetirizine, and
      diphenhydramine increased apo A-I levels in a dose-dependent manner while
      treatment with H2 receptor antagonists including cimetidine, famotidine, and
      ranitidine had no effect. We conclude that H1 receptor signaling is a novel
      pathway of apo A1 gene expression and therefore could be an important therapeutic
      target for enhancing de-novo apo A-1 synthesis.

PMID- 29378197
TI  - TLR7 Agonist Increases Responses of Hepatitis B Virus-Specific T Cells and
      Natural Killer Cells in Patients With Chronic Hepatitis B Treated With
      Nucleos(T)Ide Analogues.
AB  - BACKGROUND & AIMS: The oral Toll-like receptor (TLR) 7 agonist GS-9620 has
      antiviral effects in woodchuck and chimpanzee models of chronic hepatitis B virus
      (HBV) infection. We investigated, in a clinical trial, the capacity of this agent
      to reconstitute protective immunity in patients with chronic HBV infection.
      METHODS: We performed a prospective study of 28 patients with suppression of HBV
      infection by nucleos(t)ide analogue therapy and who tested negative for hepatitis
      B e antigen at 4 medical centers in Italy. Patients were randomly assigned
      (1:3:3:3) to groups given placebo or different doses of GS-9620 (1, 2, and 4 mg,
      weekly for 12 weeks). We added data from 8 patients receiving nucleos(t)ide
      analogue therapy to the placebo group (controls); 13 treatment-naive patients
      with chronic HBV infection and 15 subjects who spontaneously recovered from an
      acute HBV infection served as additional controls. Peripheral blood mononuclear
      cells were collected at baseline, during administration of GS-9620 or placebo,
      and 12 weeks afterward. Phenotype and function of natural killer (NK) and HBV
      specific T cells were analyzed by flow cytometry. T cells were expanded by
      incubation with peptides from the entire HBV proteome and studied after overnight
      or 10 days culture. NK-cell inhibition of T-cell responses was measured by
      assessing cytokine production by T cells stimulated with peptides in the presence
      or absence of NK cells. RESULTS: T cells collected at baseline before addition of
      GS-9620, when patients were receiving only nucleos(t)ide therapy, had greater
      responses to HBV than T cells from treatment-naive patients, based on cytokine
      production in response to HBV peptides. However, during or after administration
      of GS-9620, T cells produced higher levels of cytokines compared to baseline. NK
      cell activation and function increased after patients were given GS-9620, but the
      ability of NK cells to suppress T-cell responses was lower during GS-9620 therapy
      than before. Changes in T-cell or NK-cell function did not correlate with levels
      of hepatitis B surface antigen. Serum levels of hepatitis B surface antigen did
      not decrease significantly compared to baseline in patients given any dose of GS
      9620. CONCLUSIONS: Twelve weeks administration of GS-9620 had no significant
      effect on serum hepatitis B surface antigen levels, but did appear to increase T
      cell and NK-cell responses and reduce the ability of NK to suppress T cells. GS
      9620 might therefore be included in therapies to increase the immune response to
      HBV.

PMID- 29378198
TI  - Mutations in Mitochondrial DNA From Pancreatic Ductal Adenocarcinomas Associate
      With Survival Times of Patients and Accumulate as Tumors Progress.
AB  - Somatic mutations have been found in the mitochondria in different types of
      cancer cells, but it is not clear whether these affect tumorigenesis or tumor
      progression. We analyzed mitochondrial genomes of 268 early-stage, resected
      pancreatic ductal adenocarcinoma tissues and paired non-tumor tissues. We defined
      a mitochondrial somatic mutation (mtSNV) as a position where the difference in
      heteroplasmy fraction between tumor and normal sample was >=0.2. Our analysis
      identified 304 mtSNVs, with at least 1 mtSNV in 61% (164 of 268) of tumor
      samples. The noncoding control region had the greatest proportion of mtSNVs (60
      of 304 mutations); this region contains sites that regulate mitochondrial DNA
      transcription and replication. Frequently mutated genes included ND5, RNR2, and
      CO1, plus 29 mutations in transfer RNA genes. mtSNVs in 2 separate mitochondrial
      genes (ND4 and ND6) were associated with shorter overall survival time. This
      association appeared to depend on the level of mtSNV heteroplasmy. Non-random co
      occurrence between mtSNVs and mutations in nuclear genes indicates interactions
      between nuclear and mitochondrial DNA. In an analysis of primary tumors and
      metastases from 6 patients, we found tumors to accumulate mitochondrial
      mutational mutations as they progress.

PMID- 29378199
TI  - Iron-induced oxidative stress stimulates osteoclast differentiation via NF-kappaB
      signaling pathway in mouse model.
AB  - BACKGROUND: Women transitioned to postmenopausal status experience a
      corresponding gain in iron stores. Recently clinical researches have observed
      increased serum ferritin level in postmenopausal women, and ferritin level was
      negatively correlated with bone mineral density. PURPOSE: To explore the
      mechanism of iron-induced osteopenia in mouse model. METHODS: Briefly, in this
      study, we established an iron accumulation mouse model with ovariectomy. Primary
      osteoclasts and osteoblasts were extracted for this research. Biomarkers of bone
      metabolism and cell signaling pathways were measured. RESULTS: We found that bone
      mass changed later than ferritin and decreased gradually following overiectomy.
      We also observed higher levels of bone resorption and oxidative stress when iron
      was administered. When stimulated with iron, primary osteoclasts derived from
      bone marrow-derived macrophages (BMMs) underwent differentiation and numerous
      reactive oxygen species (ROS) were generated. Further, we found that iron
      activated the JNK, ERK and NF-kappaB signaling pathways in vivo. In vitro, we
      found that only NF-kappaB signaling was stimulated by iron and that suppression
      of this pathway blocked osteoclast differentiation. To determine whether these
      effects were related to ROS, osteoclasts were treated with H2O2. We found that
      ROS stimulated osteoclast activity, and that this effect was reversed upon NF
      kappaB suppression. CONCLUSIONS: These data suggest that ROS might be a
      downstream factor of iron and regulated NF-kappaB signaling in osteoclasts in
      mouse model.

PMID- 29378200
TI  - Research advances in metabolism 2017.

PMID- 29378201
TI  - Hidradenitis Suppurativa Is Associated with Polycystic Ovary Syndrome: A
      Population-Based Analysis in the United States.
AB  - Polycystic ovary syndrome (PCOS) has been linked to hidradenitis suppurativa
      (HS). However, evidence establishing a relationship between the two conditions is
      limited. We sought to determine the prevalence of PCOS among patients with HS and
      the strength of the association. We performed a cross-sectional analysis
      involving 22,990 patients with HS using clinical data from a multihealth system
      analytics platform comprising more than 55 million unique patients across all
      census regions of the United States. The prevalence of PCOS among patients with
      HS was 9.0%, compared with 2.9% in patients without HS (P < 0.0001). The
      likelihood of patients with HS having PCOS was 2.14 (95% confidence interval 2.04
      2.24) times that of patients without HS, and PCOS was associated with HS across
      all subgroups. The strength of the HS association with PCOS was similar to that
      of diabetes mellitus (odds ratio 2.88, 95% confidence interval 2.83-2.93) and
      obesity (odds ratio 3.93, 95% confidence interval 3.87-3.99) with PCOS. The
      influence of disease severity on the strength of association with PCOS could not
      be assessed, nor could an HS phenotype for patients also having PCOS. This
      analysis could not establish directionality of relationship, nor causal link. In
      conclusion, PCOS is associated with HS, and patients with HS who have symptoms or
      signs of androgen excess should be screened for PCOS.

PMID- 29378202
TI  - De novo assembly of honey bee RNA viral genomes by tapping into the innate insect
      antiviral response pathway.
AB  - Bee pollination is critical for improving productivity of one third of all plants
      or plant products consumed by humans. The health of honey bees is in decline in
      many countries worldwide, and RNA viruses together with other biological,
      environmental and anthropogenic factors have been identified as the main causes.
      The rapid genetic variation of viruses represents a challenge for diagnosis.
      Thus, application of deep sequencing methods for detection and analysis of
      viruses has increased over the last years. In this study, we leverage from the
      innate Dicer-2 mediated antiviral response against viruses to reconstruct
      complete viral genomes using virus-derived small interfering RNAs (vsiRNAs).
      Symptomatic A. mellifera larvae collected from hives free of Colony Collapse
      Disorder (CCD) and the parasitic Varroa mite (Varroa destructor) were used to
      generate more than 107 million small RNA reads. We show that de novo assembly of
      insect viral sequences is less fragmented using only 22 nt long vsiRNAs rather
      than a combination of 21-22 nt small RNAs. Our results show that A. mellifera
      larvae activate the RNAi immune response in the presence of Sacbrood virus (SBV).
      We assembled three SBV genomes from three individual larvae from different hives
      in a single apiary, with 1-2% nucleotide sequence variability among them. We
      found 3-4% variability between SBV genomes generated in this study and earlier
      published Australian variants suggesting the presence of different SBV
      quasispecies within the country.

PMID- 29378203
TI  - Comparative analysis of the susceptibility/tolerance of Spodoptera littoralis to
      Vip3Aa, Vip3Ae, Vip3Ad and Vip3Af toxins of Bacillus thuringiensis.
AB  - The cotton leaf worm Spodoptera littoralis is known for causing serious damages
      to various crops. In this study, the susceptibility/tolerance of this larvae to
      four Vip3A (Vip3Aa, Vip3Ae, Vip3Ad and Vip3Af) toxins was investigated.
      UnlikeVip3Ad which showed no activity to S. littoralis, Vip3Aa, Vip3Ae and Vip3Af
      exhibited high toxicity to this larva with LC50 of 228.42 ng/cm2, 65.71 ng/cm2,
      and 388.90 ng/cm2, respectively. Activation of the 90 kDa Vip3A proteins by S.
      littoralis larvae juice generated four major bands of sizes 62, 45, 33 and 22
      kDa. Binding experiments between biotinylated Vip3A toxins and the brush border
      membrane vesicles (BBMV) revealed two binding proteins of 55 and 100 kDa with
      Vip3Aa. Vip3Ae and Vip3Af recognized one single putative receptor of 65 kDa,
      whereas Vip3Ad did not bind to S. littoralis BBMV. In histopathological
      observations, Vip3Aa, Vip3Ae and Vip3Af toxins showed approximately similar
      damages on S. littoralis midgut including rupture and disintegration of
      epithelial layer and cellular vacuolization. These findings showed that Vip3Aa,
      Vip3Ae and Vip3Af might be useful for controlling S. littoralis.

PMID- 29378204
TI  - Glial cells as mediators of protective actions of prolactin (PRL) in the CNS.
AB  - Prolactin (PRL) is a hormone with multiple actions in the central nervous system
      (CNS) spanning from physiology to pathology. PRL exerts different actions through
      its receptors that can be found in both neurons and glial cells (astrocytes,
      microglia and oligodendrocytes) of the brain. Even though its effects during
      pregnancy and lactation, stress, anxiety, and depression are well studied, recent
      work on this hormone has brought to light a new role of PRL: that of a protective
      agent against brain damage and, consequently, against neurodegeneration. The
      mechanisms through which this protection takes place have not been fully
      elucidated; however, neurogenesis and anti-apoptosis are some of the plausible
      mechanisms that could mediate this effect. There is substantial information that
      implies the involvement of glial activation in this PRL effect, as shown in
      various models of brain damage. Taking into account glial cell dynamics and
      actions in various pathological conditions, combined with the neuroprotective
      effect of PRL, we consider of importance the revision of all the information
      about the interaction between these two cell types, as it will provide
      comprehensive knowledge about this new target of PRL against neuropathology.

PMID- 29378205
TI  - Coordinated neural, behavioral, and phenomenological changes in perceptual
      plasticity through overtraining of synesthetic associations.
AB  - Synesthesia is associated with additional perceptual experiences, which are
      automatically and consistently triggered by specific inducing stimuli.
      Synesthesia is also accompanied by more general sensory and cortical changes,
      including enhanced modality-specific cortical excitability. Extensive cognitive
      training has been shown to generate synesthesia-like phenomenology but whether
      these experiences are accompanied by neurophysiological changes characteristic of
      synesthesia remains unknown. Addressing this question provides a unique
      opportunity to elucidate the neural basis of perceptual plasticity relevant to
      conscious experiences. Here we investigate whether extensive training of letter
      color associations leads not only to synesthetic experiences, but also to changes
      in cortical excitability. We confirm that overtraining synesthetic associations
      results in synesthetic phenomenology. Stroop tasks further reveal synesthesia
      like performance following training. Electroencephalography and transcranial
      magnetic stimulation show, respectively, enhanced visual evoked potentials (in
      response to untrained patterns) and lower phosphene thresholds, demonstrating
      specific cortical changes. An active (using letter-symbol training) and a passive
      control confirmed these results were due to letter-color training and not simply
      to repeated testing. Summarizing, we demonstrate specific cortical changes,
      following training-induced acquisition of synesthetic phenomenology that are
      characteristic of genuine synesthesia. Collectively, our data reveal dramatic
      plasticity in human visual perception, expressed through a coordinated set of
      behavioral, neurophysiological, and phenomenological changes.

PMID- 29378206
TI  - PSRC1 overexpression attenuates atherosclerosis progression in apoE-/- mice by
      modulating cholesterol transportation and inflammation.
AB  - AIMS: Human genome-wide association studies (GWAS) have found that proline/serine
      rich coiled-coil 1 (PSRC1) encodes a protein that is associated with serum lipid
      levels and coronary artery disease. In addition, our previous study showed that
      the cholesterol efflux capacity is decreased in macrophages following a treatment
      silencing Psrc1, indicating that PSRC1 has anti-atherosclerotic effects. However,
      the role of PSRC1 in the development of atherosclerosis is unknown. This study
      aims to explore the effect of PSRC1 on atherosclerosis and its underlying
      mechanisms. METHOD AND RESULTS: A recombinant adenovirus expressing Psrc1 (Ad
      PSRC1) was constructed and transfected in RAW264.7 cells as well as injected
      intravenously into apoE-/- mice. The in vitro study showed that PSRC1
      overexpression reduced the cellular cholesterol content, increased the
      cholesterol efflux capacity and inhibited foam cell formation by upregulating the
      expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and
      liver X receptor alpha (LXR-alpha), which are key cholesterol transportation
      related proteins. Infecting apoE-/- mice with Ad-PSRC1 inhibited the development
      of atherosclerotic lesions and enhanced atherosclerotic plaque stability.
      Consistent with these results, PSRC1 overexpression in apoE-/- mice decreased the
      plasma levels of TC, TG, LDL-C, TNF-alpha, IL-1beta and IL-6, increased the
      plasma HDL-C levels and improved HDL function. Similarly, the PPAR-gamma and LXR
      alpha expression levels were upregulated in the liver and in peritoneal
      macrophages of PSRC1-overexpressing apoE-/- mice. Finally, the liver and
      peritoneal macrophages of apoE-/- mice displayed elevated expression of beta
      catenin, which is a direct downstream gene of PSRC1 and an upstream gene of PPAR
      gamma and LXR-alpha, but decreased activity of nuclear transcription factor (NF
      kappaB), which acts as a key gene in the regulation of inflammation. CONCLUSIONS:
      PSRC1 protects against the development of atherosclerosis and enhances the
      stability of plaques by modulating cholesterol transportation and inflammation in
      macrophages and the liver of apoE-/- mice.

PMID- 29378207
TI  - Sex-biased transcriptomic response of the reproductive axis to stress.
AB  - Stress is a well-known cause of reproductive dysfunction in many species,
      including birds, rodents, and humans, though males and females may respond
      differently. A powerful way to investigate how stress affects reproduction is by
      examining its effects on a biological system essential for regulating
      reproduction, the hypothalamic-pituitary-gonadal (HPG) axis. Often this is done
      by observing how a stressor affects the amount of glucocorticoids, such as
      cortisol or corticosterone, circulating in the blood and their relationship with
      a handful of known HPG-producing reproductive hormones, like testosterone and
      estradiol. Until now, we have lacked a full understanding of how stress affects
      all genomic activity of the HPG axis and how this might differ between the sexes.
      We leveraged a highly replicated and sex-balanced experimental approach to test
      how male and female rock doves (Columba livia) respond to restraint stress at the
      level of their transcriptome. Females exhibit increased genomic responsiveness to
      stress at all levels of their HPG axis as compared to males, and these responsive
      genes are mostly unique to females. Reasons for this may be due to fluctuations
      in the female endocrine environment over the reproductive cycle and/or their
      evolutionary history, including parental investment and the potential for
      maternal effects. Direct links between genome to phenome cause and effect cannot
      be ascertained at this stage; however, the data we report provide a vital genomic
      foundation on which sex-specific reproductive dysfunction and adaptation in the
      face of stress can be further experimentally studied, as well as novel gene
      targets for genetic intervention and therapy investigations.

PMID- 29378208
TI  - An epigenetic basis for an omnigenic model of psychiatric disorders.

PMID- 29378209
TI  - Methylphenidate ameliorates hypoxia-induced mitochondrial damage in human
      neuroblastoma SH-SY5Y cells through inhibition of oxidative stress.
AB  - AIMS: Methylphenidate (MPH) is a dopamine-reuptake inhibitor approved for the
      treatment of attention-deficit/hyperactivity disorder (ADHD). Nonetheless, the
      cellular and molecular mechanisms of MPH are still unknown. We attempt to
      determine whether MPH protect neuron cells against oxidative stress by using
      human neuroblastoma SH-SY5Y cells. MAIN METHODS: The SH-SY5Y cells were cultured
      in normoxic and hypoxic conditions in the presence of different doses of MPH.
      Then, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH),
      superoxide dismutase (SOD) and adenosine triphosphate (ATP) production were
      quantitatively measured by using flow cytometry or spectrophotometry. The
      mitochondrial ultrastructure of the cells was observed by electron microscope,
      and the function of mitochondrial was evaluated by measuring mitochondrial
      membrane potential (MMP) using flow cytometry. The levels of SOD and heme
      oxygenase-1 (HO-1) proteins were detected by Western blot. KEY FINDINGS: We found
      that low doses of MPH treatment (50-500 ng/mL) led to decreased ROS and MDA
      production (P<0.05), increased GSH and SOD as well as ATP concentration (P<0.05)
      in hypoxic SH-SY5Y cells. Additionally, low doses of MPH significantly inhibited
      mitochondrial swelling and decreased the percentage of JC-1 monomer positive
      cells. However, we did not observe the same effects of MPH in normoxia.
      SIGNIFICANCE: Our results show that low doses of MPH play protective roles in
      maintaining mitochondrial homeostasis in response to hypoxia-induced oxidative
      stress. Our findings may provide novel insight into the mechanisms of MPH in the
      treatment of ADHD, and shed light on the disease mechanisms of ADHD.

PMID- 29378210
TI  - Facilitated AMPAR endocytosis causally contributes to the maternal sleep
      deprivation-induced impairments of synaptic plasticity and cognition in the
      offspring rats.
AB  - Maternal sleep deprivation (MSD) has been suggested to be associated with
      increased frequency of neurodevelopmental disorders in offspring in both humans
      and animal models. However, the underlying cellular and molecular mechanism is
      still unclear. We have recently reported that MSD at different stages of
      pregnancy impairs the emotional and cognitive functions, and suppresses
      hippocampal CA1 long-term potentiation (LTP) in the offspring rats. Here, we
      report that the MSD induced LTP impairment at the CA1 hippocampus of the
      offspring rats is associated with increased long-term depression (LTD) and
      reduced expression of postsynaptic GluA2-containing alpha-amino-3-hydroxy-5
      methyl-isoxazole-4-propionic acid receptors (AMPARs). Importantly, we found that
      inhibition of AMPAR endocytosis by a synthetic peptide Tat-GluA23Y (3 MUmol/kg,
      i.p.) not only increased level of AMPARs and reduced LTD, but also restored LTP.
      Moreover, treatment with Tat-GluA23Y peptide markedly alleviated the MSD-induced
      impairments of spatial learning and memory; and decreased depressive- and anxiety
      like behaviors in the offspring. Together, our findings suggest that the MSD
      induced postsynaptic AMPAR endocytosis causally contributes to the impairments of
      hippocampal synaptic plasticity, thereby disrupting the emotional and cognitive
      functions in the offspring.

PMID- 29378211
TI  - Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces
      ethanol consumption and relapse in rat.
AB  - Addiction is a chronic and highly relapsing disorder hypothesized to be produced
      by an imbalance between excitatory and inhibitory neurotransmission. For more
      than a decade, emerging evidence indicates that manipulation of glutamatergic
      neurotransmission, by group III mGlu receptors (mGlu4/7/8), could be a promising
      approach to develop therapeutic agents for the treatment of addiction. Thus, the
      aim of the present study is to determine whether LSP2-9166, a mixed mGlu4/mGlu7
      orthosteric agonist, could reduce ethanol self-administration, ethanol motivation
      and reacquisition after protracted abstinence in a preclinical model of excessive
      ethanol intake. Male Long Evans rats were chronically trained to consume large
      amount of ethanol in operant cages for several weeks. Once they reached a stable
      level of consumption (about 1 g of pure ethanol/kg bodyweight/15min), the effect
      of LSP2-9166 was evaluated on different aspects of the operant self
      administration behavior. In this study, we found that the intracerebroventricular
      infusion of LSP2-9166 dose dependently reduced ethanol consumption, motivation
      for ethanol and reacquisition of ethanol self-administration after abstinence.
      Together, these results support recent preclinical findings showing that
      pharmacological modulation of mGlu receptors may serve as an effective treatment
      for reducing ethanol consumption and relapse.

PMID- 29378212
TI  - Systemic blockade of LPA1/3 lysophosphatidic acid receptors by ki16425 modulates
      the effects of ethanol on the brain and behavior.
AB  - The systemic administration of lysophosphatidic acid (LPA) LPA1/3 receptor
      antagonists is a promising clinical tool for cancer, sclerosis and fibrosis
      related diseases. Since LPA1 receptor-null mice engage in increased ethanol
      consumption, we evaluated the effects of systemic administration of an LPA1/3
      receptor antagonist (intraperitoneal ki16425, 20 mg/kg) on ethanol-related
      behaviors as well as on brain and plasma correlates. Acute administration of
      ki16425 reduced motivation for ethanol but not for saccharine in ethanol self
      administering Wistar rats. Mouse experiments were conducted in two different
      strains. In Swiss mice, ki16425 treatment reduced both ethanol-induced sedation
      (loss of righting reflex, LORR) and ethanol reward (escalation in ethanol
      consumption and ethanol-induced conditioned place preference, CPP). Furthermore,
      in the CPP-trained Swiss mice, ki16425 prevented the effects of ethanol on basal
      c-Fos expression in the medial prefrontal cortex and on adult neurogenesis in the
      hippocampus. In the c57BL6/J mouse strain, however, no effects of ki16425 on LORR
      or voluntary drinking were observed. The c57BL6/J mouse strain was then evaluated
      for ethanol withdrawal symptoms, which were attenuated when ethanol was preceded
      by ki16425 administration. In these animals, ki16425 modulated the expression of
      glutamate-related genes in brain limbic regions after ethanol exposure; and
      peripheral LPA signaling was dysregulated by either ki16425 or ethanol. Overall,
      these results suggest that LPA1/3 receptor antagonists might be a potential new
      class of drugs that are suitable for treating or preventing alcohol use
      disorders. A pharmacokinetic study revealed that systemic ki16425 showed poor
      brain penetration, suggesting the involvement of peripheral events to explain its
      effects.

PMID- 29378215
TI  - Roles of TRAFs in NF-kappaB signaling pathways mediated by BAFF.
AB  - B cell activating factor (BAFF) is an important cytokine for the maintenance of B
      cell development, survival and homeostasis. BAFF/BAFF-R could directly activate
      nuclear factor kappa B (NF-kappaB) pathway. Tumour necrosis factor receptor
      associated factors (TRAFs) are key regulatory proteins in NF-kappaB signaling
      pathways. TRAF1 enhances the activation of tumor necrosis factor receptor 2 (TNF
      R2) induced by NF-kappaB. TRAF2 and TRAF3 signal adapters act cooperatively to
      control the maturation and survival signals mediated by BAFF receptor. TRAF5 is
      most homologous to TRAF3, as well as most functionally similar to TRAF2. TRAF6 is
      also required for the BAFF-mediated activation of NF-kappaB signal pathway. TRAF7
      is involved in signal transduction pathways that lead either to activation or
      repression of NF-kappaB transcription factor. In this article, we reviewed the
      roles of TRAFs in NF-kappaB signaling pathway mediated by BAFF.

PMID- 29378213
TI  - "Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic
      cathinone analogs of MDMA.
AB  - This study aimed to address the mechanisms and reinforcing effects of three
      synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations:
      methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used
      to assess the mechanism of each compound at the dopamine and serotonin
      transporters. Separate groups of rats were trained to discriminate
      methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed
      in each group and antagonism studies with SCH23390 were performed against each
      compound that produced substitution. Self-administration of each compound was
      evaluated under a progressive ratio schedule of reinforcement. Each compound
      produced an inward current at the serotonin transporter, but little or no current
      at the dopamine transporter. Each of the test compounds substituted fully for the
      discriminative stimulus effects of methamphetamine, methylone and butylone
      substituted partially for DOM and fully for MDMA, whereas pentylone failed to
      substitute for DOM and substituted only partially for MDMA. SCH23390 fully and
      dose-dependently attenuated methamphetamine-appropriate responding produced by
      each test compound, but was least potent against pentylone. MDMA-appropriate
      responding was minimally affected by SCH23390. Each test compound was robustly
      self-administered with pentylone producing the greatest self-administration at
      the doses tested. Given the prevalence of synthetic cathinones in "Ecstasy"
      formulations, these data indicate that adulterated "Ecstasy" formulations may
      drive more compulsive drug use than those containing only MDMA.

PMID- 29378214
TI  - Activation of neural stem cells from quiescence drives reactive hippocampal
      neurogenesis after alcohol dependence.
AB  - Neural stem cell-driven adult neurogenesis contributes to the integrity of the
      hippocampus. Excessive alcohol consumption in alcoholism results in hippocampal
      degeneration that may recover with abstinence. Reactive, increased adult
      neurogenesis during abstinence following alcohol dependence may contribute to
      recovery, but the mechanism driving reactive neurogenesis is not known.
      Therefore, adult, male rats were exposed to alcohol for four days and various
      markers were used to examine cell cycle dynamics, the percentage and number of
      neural progenitor cell subtypes, and the percentage of quiescent versus activated
      progenitors. Using a screen for cell cycle perturbation, we showed that the cell
      cycle is not likely altered at 7 days in abstinence. As the vast majority of
      Bromodeoxyuridine-positive (+) cells were co-labeled with progenitor cell marker,
      Sox2, we then developed a quadruple fluorescent labeling scheme to examine Type
      1, -2a, -2b and -3 progenitor cells simultaneously. Prior alcohol dependence
      indiscriminately increased all subtypes at 7 days, the peak of the reactive
      proliferation. An evaluation of the time course of reactive cell proliferation
      revealed that cells begin proliferating at 5 days post alcohol, where only
      actively dividing Type 2 progenitors were increased by alcohol. Furthermore,
      prior alcohol increased the percentage of actively dividing Sox2+ progenitors,
      which supported that reactive neurogenesis is likely due to the activation of
      progenitors out of quiescence. These observations were associated with granule
      cell number returning to normal at 28 days. Therefore, activating stem and
      progenitor cells out of quiescence may be the mechanism underlying hippocampal
      recovery in abstinence following alcohol dependence.

PMID- 29378216
TI  - Junctional adhesion molecule C (JAM-C) dimerization aids cancer cell migration
      and metastasis.
AB  - Most cancer deaths result from metastasis, which is the dissemination of cells
      from a primary tumor to distant organs. Metastasis involves changes to molecules
      that are essential for tumor cell adhesion to the extracellular matrix and to
      endothelial cells. Junctional Adhesion Molecule C (JAM-C) localizes at
      intercellular junctions as homodimers or more affine heterodimers with JAM-B. We
      previously showed that the homodimerization site (E66) in JAM-C is also involved
      in JAM-B binding. Here we show that neoexpression of JAM-C in a JAM-C-negative
      carcinoma cell line induced loss of adhesive property and pro-metastatic
      capacities. We also identify two critical structural sites (E66 and K68) for JAM
      C/JAM-B interaction by directed mutagenesis of JAM-C and studied their
      implication on tumor cell behavior. JAM-C mutants did not bind to JAM-B or
      localize correctly to junctions. Moreover, mutated JAM-C proteins increased
      adhesion and reduced proliferation and migration of lung carcinoma cell lines.
      Carcinoma cells expressing mutant JAM-C grew slower than with JAM-C WT and were
      not able to establish metastatic lung nodules in mice. Overall these data
      demonstrate that the dimerization sites E66-K68 of JAM-C affected cell adhesion,
      polarization and migration and are essential for tumor cell metastasis.

PMID- 29378217
TI  - Ultrasonography during CPR: Hands-off or hands-on?

PMID- 29378218
TI  - Ensemble support vector machine classification of dementia using structural MRI
      and mini-mental state examination.
AB  - BACKGROUND: The International Challenge for Automated Prediction of MCI from MRI
      data offered independent, standardized comparison of machine learning algorithms
      for multi-class classification of normal control (NC), mild cognitive impairment
      (MCI), converting MCI (cMCI), and Alzheimer's disease (AD) using brain imaging
      and general cognition. NEW METHOD: We proposed to use an ensemble of support
      vector machines (SVMs) that combined bagging without replacement and feature
      selection. SVM is the most commonly used algorithm in multivariate classification
      of dementia, and it was therefore valuable to evaluate the potential benefit of
      ensembling this type of classifier. RESULTS: The ensemble SVM, using either a
      linear or a radial basis function (RBF) kernel, achieved multi-class
      classification accuracies of 55.6% and 55.0% in the challenge test set (60 NC, 60
      MCI, 60 cMCI, 60 AD), resulting in a third place in the challenge. Similar
      feature subset sizes were obtained for both kernels, and the most frequently
      selected MRI features were the volumes of the two hippocampal subregions left
      presubiculum and right subiculum. Post-challenge analysis revealed that enforcing
      a minimum number of selected features and increasing the number of ensemble
      classifiers improved classification accuracy up to 59.1%. COMPARISON WITH
      EXISTING METHOD(S): The ensemble SVM outperformed single SVM classifications
      consistently in the challenge test set. CONCLUSIONS: Ensemble methods using
      bagging and feature selection can improve the performance of the commonly applied
      SVM classifier in dementia classification. This resulted in competitive
      classification accuracies in the International Challenge for Automated Prediction
      of MCI from MRI data.

PMID- 29378219
TI  - Meroterpenoids from the fruiting bodies of Ganoderma theaecolum.
AB  - A series of new terminal cyclohexane-type meroterpenoids, ganotheaecoloids A-N (1
      6, 8-13, 15, and 16), along with three known ones (7, 14, and 17), were isolated
      from the dried fruiting bodies of Ganoderma theaecolum. Their chemical structures
      were identified by using spectroscopic data and computational methods. Biological
      activity of all the new meroterpenoids against COX-2 was evaluated in vitro, only
      ganotheaecoloid J (11) was found to have COX-2 inhibitory activity with IC50
      value of 9.96MUM.

PMID- 29378221
TI  - Canine sarcomas as a surrogate for the human disease.
AB  - Pet dogs are becoming increasingly recognized as a population with the potential
      to inform medical research through their treatment for a variety of maladies by
      veterinary health professionals. This is the basis of the One Health initiative,
      supporting the idea of collaboration between human and animal health researchers
      and clinicians to study spontaneous disease processes and treatment in animals to
      inform human health. Cancer is a major health burden in pet dogs, accounting for
      approximately 30% of deaths across breeds. As such, pet dogs with cancer are
      becoming increasingly recognized as a resource for studying the pharmacology and
      therapeutic potential of anticancer drugs and therapies under development. This
      was recently highlighted by a National Academy of Medicine Workshop on
      Comparative Oncology that took place in mid-2015 (http://www.nap.edu/21830). One
      component of cancer burden in dogs is their significantly higher incidence of
      sarcomas as compared to humans. This increased incidence led to canine
      osteosarcoma being an important component in the development of surgical
      approaches for osteosarcoma in children. Included in this review of sarcomas in
      dogs is a description of the incidence, pathology, molecular characteristics and
      previous translational therapeutic studies associated with these tumors. An
      understanding of the patho-physiological and molecular characteristics of these
      naturally occurring canine sarcomas holds great promise for effective
      incorporation into drug development schemas, for evaluation of target modulation
      or other pharmacodynamic measures associated with therapeutic response. These
      data could serve to supplement other preclinical data and bolster clinical
      investigations in tumor types for which there is a paucity of human patients for
      clinical trials.

PMID- 29378220
TI  - Thyroid hormone and the brain: Mechanisms of action in development and role in
      protection and promotion of recovery after brain injury.
AB  - Thyroid hormone (TH) is essential for normal brain development and may also
      promote recovery and neuronal regeneration after brain injury. TH acts
      predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta
      (THRB). Additional factors that impact TH action in the brain include metabolism,
      activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5'-deiodinase
      Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse
      T3 (rT3), which occurs in glial cells, and uptake by the Mct8 transporter in
      neurons. Traumatic brain injury (TBI) is associated with inflammation, metabolic
      alterations and neural death. In clinical studies, central hypothyroidism, due to
      hypothalamic and pituitary dysfunction, has been found in some individuals after
      brain injury. TH has been shown, in animal models, to be protective for the
      damage incurred from brain injury and may have a role to limit injury and promote
      recovery. Although clinical trials have not yet been reported, findings from in
      vitro and in vivo models inform potential treatment strategies utilizing TH for
      protection and promotion of recovery after brain injury.

PMID- 29378222
TI  - Carvacrol prevents impairments in motor and neurochemical parameters in a model
      of progressive parkinsonism induced by reserpine.
AB  - Parkinson's disease (PD) is a neurodegenerative disease characterized by a
      progressive degeneration of dopaminergic neurons in the substantia nigra pars
      compact (SNpc), with consequent depletion of dopamine in the striatum, which
      gives rise to the characteristic motor symptoms of PD. Although its etiology is
      unknown, several studies have suggested that oxidative stress plays a critical
      function in the pathophysiology of PD, and antioxidant agents could be helpful to
      slown down the dopaminergic neurodegeneration. Carvacrol (CA) is a phenolic
      monoterpene found in essential oils of many aromatic plants that presents
      antioxidant and neuroprotective effects. This study aimed to assess the effect of
      CA in a reserpine (RES)-induced rat model of PD. Male Wistar rats received 15
      s.c. injections of 0.1 mg/kg RES or vehicle, every other day, concomitantly to
      daily i.p. injections of CA (12.5 or 25 mg/kg) or vehicle. Across the treatment,
      the animals were submitted to behavioral evaluation in the catalepsy test
      (performed daily), open field test (7th day) and assessment of vacuous chewing
      movements (12th, 20th and 30th days). Upon completion of behavioral tests, rats
      were perfused and their brains underwent tyrosine hydroxylase (TH)
      immunohistochemical analysis. Our results showed that CA (12.5 e 25 mg/kg)
      prevented the increase in catalepsy behavior and number of vacuous chewing
      movements, but failed to revert the decreased open-field locomotor activity
      induced by RES. In addition, CA in both doses prevented the decrease in TH
      immunostaining induced by RES in the SNpc and dorsal striatum. Taken together,
      our results suggest that CA shows a protective effect in a rat model of PD,
      preventing motor and neurochemical impairments induced by RES. Thus, the use of
      CA as a promising new strategy for the prevention and/or treatment of PD may be
      considered.

PMID- 29378223
TI  - Principles of diffusion kurtosis imaging and its role in early diagnosis of
      neurodegenerative disorders.
AB  - Pathology of neurodegenerative diseases can be correlated with intra-neuronal as
      well as extracellular changes which lead to neuronal degeneration. The central
      nervous system (CNS) is a complex structure comprising of many biological
      barriers. These microstructural barriers might be affected by a variety of
      pathological processes. Specifically, changes in the brain tissue's
      microstructure affect the diffusion of water which can be assessed non-invasively
      by diffusion weighted (DW) magnetic resonance imaging (MRI) techniques. Diffusion
      tensor imaging (DTI) is a diffusion MRI technique that considers diffusivity as a
      Gaussian process, i.e. does not account for any diffusion hindrance. However,
      environment of the brain tissues is characterized by a non-Gaussian diffusion.
      Therefore, diffusion kurtosis imaging (DKI) was developed as an extension of DTI
      method in order to quantify the non-Gaussian distribution of water diffusion.
      This technique represents a promising approach for early diagnosis of
      neurodegenerative diseases when the neurodegenerative process starts. Hence, the
      purpose of this article is to summarize the ongoing clinical and preclinical
      research on Parkinson's, Alzheimer's and Huntington diseases, using DKI and to
      discuss the role of this technique as an early stage biomarker of
      neurodegenerative conditions.

PMID- 29378224
TI  - Forces maintaining the DNA double helix and its complexes with transcription
      factors.
AB  - Precise calorimetric studies of DNA duplexes of various length and composition
      have revised several long-held beliefs about the forces holding together the
      double helix and its complexes with the DNA binding domains (DBDs) of
      transcription factors. Heating DNA results in an initial non-cooperative increase
      of torsional oscillations in the duplex, leading to cooperative dissociation of
      its strands accompanied by extensive heat absorption and a significant heat
      capacity increment. The enthalpy and entropy of duplex dissociation are therefore
      temperature dependent quantities. When compared at the same temperature the
      enthalpic and entropic contributions the CG base pair are less than that of the
      AT pair - not more as previously assumed from the extra hydrogen bond. Thus the
      stabilizing effect of the CG base pair comes from its smaller entropic
      contribution. The greater enthalpic and entropic contributions of the AT pair
      result from water fixed by its polar groups in the minor groove of DNA. This
      water is also responsible for the so-called "nearest-neighbour effects" used to
      explain the sequence-dependent stabilities of DNA duplexes. Removal of this water
      by binding DBDs to the minor groove makes this an entropy driven process, in
      contrast to major groove binding which is enthalpy driven. Analysis of the forces
      involved in maintaining DNA-DBD complexes shows that specificity of DBD binding
      is provided by enthalpic interactions, while the electrostatic component that
      results from counter-ion dispersal is entirely entropic and not sequence
      specific. Although the DNA double helix is a rather rigid construction, binding
      of DBDs to its minor groove often results in considerable DNA bending without the
      expenditure of significant free energy. This suggests that the rigidity of the
      DNA duplex comes largely from the water fixed to AT pairs in the minor groove,
      the loss of which then enables sharp bending.

PMID- 29378225
TI  - Influence of the loci of non-cavitated fissure caries on its detection with
      optical coherence tomography.
AB  - OBJECTIVE: The main objective of this study was to evaluate the accuracy of
      optical coherence tomography (OCT) in detecting naturally occurring non-cavitated
      fissure caries (NCFC) in totality and at different loci by visually assessing
      cross-sectional OCT scans (B-scan) with an interpretation criterion. The
      secondary objective was to evaluate the agreement between dimensions of NCFC
      measured with OCT and polarized light microscopy (PLM). METHODS: 71 investigation
      sites of sound fissure and naturally occurring NCFC on human extracted premolars
      were identified and scanned with a swept-source OCT. The teeth were then
      sectioned bucco-lingually at the investigation sites and imaged using PLM. Two
      calibrated examiners trained on the B-scan NCFC visual interpretation criteria
      established for this study, assessed the investigation sites and results were
      validated against PLM. RESULTS: Detection sensitivity of B-scan for NCFC when
      fissures were assessed in totality, or on the slopes or walls separately are
      0.98, 0.95, 0.94 and specificity are 0.95, 0.90, and 0.95. One-way ANOVA showed
      that width measurements of wall loci done with OCT and PLM were not statistically
      different. However, OCT height measurements of slope loci were statistically
      bigger with a constant bias of 0.08 mm (of which is not clinically significant)
      and OCT height measurements of wall loci were statistically smaller (0.57 mm) and
      Bland-Altman plots indicated presence of proportionate bias. CONCLUSION: Visual
      assessment of B-scans with the interpretation criteria resulted in both high
      specificity and sensitivity and were not affected by loci location. OCT width
      measurement of wall loci is in agreement with PLM. CLINICAL SIGNIFICANCE:
      Unanimous high sensitivity in this and previous studies indicate that visual
      assessment of B-scans reliably rule out NCFC. Detection accuracy was not affected
      by loci location. Width of wall loci and/or height of slope loci in OCT B-scan
      are to be used for monitoring NCFC but not height of wall loci.

PMID- 29378227
TI  - The effect of acute and chronic exercise on steroid hormone fluctuations in young
      and middle-aged men.
AB  - The current study examine the effects of combined sprint and resistance training
      on serum total testosterone (TT), sex-hormone-binding globulin (SHBG) and
      cortisol (C), at rest, and in response to the Wingate Anaerobic-Test (WAnT) in 21
      and 41 years old men. Forty moderately-trained men were randomly assigned to a
      young trained (YT), young control (YC), middle-aged trained (MAT), and middle
      aged control (MAC) group. Before (P1), and after (P2) training, blood samples
      were collected at rest and after exercise. At P1, higher C and lower TT was
      observed in middle-aged groups compared to younger ones (P < 0.05). At P2, basal
      TT increased significantly (P < 0.05) in MAT and the age-difference was absent
      between trained groups (P > 0.05). Basal SHBG decreased significantly in YT at P2
      (P < 0.05) but did not change in other groups from before to after training (P >
      0.05). Free-testosterone was significantly (P < 0.05) higher in young compared to
      middle-aged groups at P1, but at P2, this age-related difference disappeared
      between YT and MAT (P > 0.05). C post-WAnT increased significantly for MAT only
      (P < 0.05) at P2, whilst no significant changes were observed in the other three
      groups (P < 0.05) at P2. In contrast, resting levels of C did not change in all
      groups at P2 (P > 0.05). The current study demonstrates that this training
      intervention may help increase steroids hormones in middle-aged men and
      counteract the negative effect of age on TT and free testosterone.

PMID- 29378226
TI  - Membrane-initiated estrogen signaling via Gq-coupled GPCR in the central nervous
      system.
AB  - The last few decades have revealed increasing complexity and depth to our
      knowledge of receptor-mediated estrogen signaling. Nuclear estrogen receptors
      (ERs) ERalpha and ERbeta remain the fundamental dogma, but recent research
      targeting membrane-bound ERs urges for a more expanded view on ER signaling.
      ERalpha and ERbeta are also involved in membrane-delineated signaling alongside
      membrane-specific G protein-coupled estrogen receptor 1 (GPER1), ER-X, and the Gq
      coupled membrane ER (Gq-mER). Membrane ERs are responsible for eliciting rapid
      responses to estrogen signaling, and their importance has been increasingly
      indicated in central nervous system (CNS) regulation of such functions as
      reproduction, energy homeostasis, and stress. While the Gq-mER signaling pathway
      is well characterized, the receptor structure and gene remains uncharacterized,
      although it is not similar to the nuclear ERalpha/beta. This review will describe
      the current knowledge of this putative membrane ER and its selective ligand, STX,
      from its initial characterization in hypothalamic melanocortin circuitry to
      recent research exploring its role in the CNS outside of the hypothalamus.

PMID- 29378229
TI  - Reformation in chimeric antigen receptor based cancer immunotherapy: Redirecting
      natural killer cell.
AB  - Natural killer (NK) cells are an important subset of lymphocytes which play a
      critical role in host immunity against cancers. With MHC-independent recognition,
      short lifespan and potent cytotoxicity, NK cells make a promising candidate for
      chimeric antigen receptor (CAR)-engineered cancer immunotherapy. Due to innate
      biological properties of NK cells, CAR-NK may outperform CAR-T therapy in terms
      of less side effects and more universal access, which may become a great
      reformation in CAR-based cancer immunotherapy. The CARs used in peripheral blood
      (PB) NK cells as well as NK cell line like NK-92 are the most important outfits
      defining antigenic specificity. The constructs of CARs used in NK cells from
      different sources vary, which all undergo generational optimization. The anti
      tumor effects of CAR-NK have been validated in numerous preclinical trials for
      cancers, including hematologic malignancies and many solid tumors, which provide
      evidence for potential clinical application of CAR-NK. Additionally, this review
      concludes the challenges faced in the application of CAR-NK. Although CAR-NK is
      considered as one of the most possible "off-the-shelf" products, the improvement
      for the efficiency of expansion and transduction as well as the solution for
      underlying safety issues is still needed. Possible coping strategies for
      challenges and upgrades in techniques are also highlighted for future development
      in CAR-NK cancer immunotherapy.

PMID- 29378230
TI  - Furocoumarins: A review of biochemical activities, dietary sources and intake,
      and potential health risks.

PMID- 29378228
TI  - The pro-tumorigenic effects of metabolic alterations in glioblastoma including
      brain tumor initiating cells.
AB  - De-regulated cellular energetics is an emerging hallmark of cancer with
      alterations to glycolysis, oxidative phosphorylation, the pentose phosphate
      pathway, lipid oxidation and synthesis and amino acid metabolism. Understanding
      and targeting of metabolic reprogramming in cancers may yield new treatment
      options, but metabolic heterogeneity and plasticity complicate this strategy. One
      highly heterogeneous cancer for which current treatments ultimately fail is the
      deadly brain tumor glioblastoma. Therapeutic resistance, within glioblastoma and
      other solid tumors, is thought to be linked to subsets of tumor initiating cells,
      also known as cancer stem cells. Recent profiling of glioblastoma and brain tumor
      initiating cells reveals changes in metabolism, as compiled here, that may be
      more broadly applicable. We will summarize the profound role for metabolism in
      tumor progression and therapeutic resistance and discuss current approaches to
      target glioma metabolism to improve standard of care.

PMID- 29378232
TI  - The frequency, antifungal susceptibility and enzymatic profiles of Candida
      species in cases of onychomycosis infection.
AB  - Although the frequency of candidal onychomycosis is increasing daily, there is
      little information in literature about the epidemiology, pathogenesis, and
      antifungal susceptibility of this dermatological disease. This study aimed to
      provide information about the epidemiology, pathogenesis, and azole
      susceptibility of Candida species isolated from patients living in a region with
      continental climate. After identification of the isolated strains using
      conventional methods, proteinase and phospholipase activities were determined by
      a plate method and biofilm-forming ability was determined using the microplate
      method. Susceptibility of the same species to fluconazole (FLU), voriconazole
      (VRC), miconazole (MNZ), itraconazole (ITZ), and ketoconazole (KTZ) were
      determined by microdilution method. The 50 Candida isolates included 23 C.
      parapsilosis (46%), 13 C. albicans (26%), 4 C. guilliermondii(8%), 4 C.tropicalis
      (8%), 2 C.krusei(2%), 1 C.lusitaniae (2%), 1 C. sake (2%), and 1 C. kefyr (2%)
      isolates. The geometric mean (GM) of the minimum inhibitory concentration (MIC)
      for FLU, KTZ, VRC, MNZ, and ITZ was 0.4 MUg/mL, 0.08 MUg/mL, 0.08 MUg/mL, 0.2
      MUg/mL, and 0.6 MUg/mL, respectively. Proteinase, phospholipase, and biofilm
      forming ability were detected in 18%(9/50), 20%(10/50), and 6%(3/50) of the
      Candida isolates, respectively. We found that the most frequently isolated
      species is C.parapsilosis. On the basis of the GM values, the most effective
      azoles are ketoconazole and voriconazole. The isolated Candida species exhibited
      low phospholipase, proteinase, and biofilm formation activities.

PMID- 29378231
TI  - RIFM fragrance ingredient safety assessment, 1,1-diethoxyisooctane, CAS Registry
      Number 69178-43-4.

PMID- 29378233
TI  - In vitro models and systems for evaluating the dynamics of drug delivery to the
      healthy and diseased brain.
AB  - The blood-brain barrier (BBB) plays a crucial role in maintaining brain
      homeostasis and transport of drugs to the brain. The conventional animal and
      Transwell BBB models along with emerging microfluidic-based BBB-on-chip systems
      have provided fundamental functionalities of the BBB and facilitated the testing
      of drug delivery to the brain tissue. However, developing biomimetic and
      predictive BBB models capable of reasonably mimicking essential characteristics
      of the BBB functions is still a challenge. In addition, detailed analysis of the
      dynamics of drug delivery to the healthy or diseased brain requires not only
      biomimetic BBB tissue models but also new systems capable of monitoring the BBB
      microenvironment and dynamics of barrier function and delivery mechanisms. This
      review provides a comprehensive overview of recent advances in microengineering
      of BBB models with different functional complexity and mimicking capability of
      healthy and diseased states. It also discusses new technologies that can make the
      next generation of biomimetic human BBBs containing integrated biosensors for
      real-time monitoring the tissue microenvironment and barrier function and
      correlating it with the dynamics of drug delivery. Such integrated system
      addresses important brain drug delivery questions related to the treatment of
      brain diseases. We further discuss how the combination of in vitro BBB systems,
      computational models and nanotechnology supports for characterization of the
      dynamics of drug delivery to the brain.

PMID- 29378234
TI  - Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: In recent years, circular RNAs (circRNAs) have been shown to
      have critical regulatory roles in cancer biology. However, the contributions of
      circRNAs to hepatocellular carcinoma (HCC) remain largely unknown. METHODS:
      cSMARCA5 (a circRNA derived from exons 15 and 16 of the SMARCA5 gene,
      hsa_circ_0001445) was identified by RNA-sequencing and validated by quantitative
      reverse transcription PCR. The role of cSMARCA5 in HCC progression was assessed
      both in vitro and in vivo. circRNAs in vivo precipitation, luciferase reporter
      assay, biotin-coupled microRNA capture and fluorescence in situ hybridization
      were conducted to evaluate the interaction between cSMARCA5 and miR-17-3p/miR
      181b-5p. RESULTS: The expression of cSMARCA5 was lower in HCC tissues, because of
      the regulation of DExH-Box Helicase 9, an abundant nuclear RNA helicase. The
      downregulation of cSMARCA5 in HCC was significantly correlated with aggressive
      characteristics and served as an independent risk factor for overall survival and
      recurrence-free survival in patients with HCC after hepatectomy. Our in vivo and
      in vitro data indicated that cSMARCA5 inhibits the proliferation and migration of
      HCC cells. Mechanistically, we found that cSMARCA5 could promote the expression
      of TIMP3, a well-known tumor suppressor, by sponging miR-17-3p and miR-181b-5p.
      CONCLUSION: These results reveal an important role of cSMARCA5 in the growth and
      metastasis of HCC and provide a fresh perspective on circRNAs in HCC progression.
      LAY SUMMARY: Herein, we studied the role of cSMARCA5, a circular RNA, in
      hepatocellular carcinoma. Our in vitro and in vivo data showed that cSMARCA5
      inhibits the growth and migration of hepatocellular carcinoma cells, making it a
      potential therapeutic target.

PMID- 29378235
TI  - Translational models of tumor angiogenesis: A nexus of in silico and in vitro
      models.
AB  - Emerging evidence shows that endothelial cells are not only the building blocks
      of vascular networks that enable oxygen and nutrient delivery throughout a tissue
      but also serve as a rich resource of angiocrine factors. Endothelial cells play
      key roles in determining cancer progression and response to anti-cancer drugs.
      Furthermore, the endothelium-specific deposition of extracellular matrix is a key
      modulator of the availability of angiocrine factors to both stromal and cancer
      cells. Considering tumor vascular network as a decisive factor in cancer
      pathogenesis and treatment response, these networks need to be an inseparable
      component of cancer models. Both computational and in vitro experimental models
      have been extensively developed to model tumor-endothelium interactions. While
      informative, they have been developed in different communities and do not yet
      represent a comprehensive platform. In this review, we overview the necessity of
      incorporating vascular networks for both in vitro and in silico cancer models and
      discuss recent progresses and challenges of in vitro experimental microfluidic
      cancer vasculature-on-chip systems and their in silico counterparts. We further
      highlight how these two approaches can merge together with the aim of presenting
      a predictive combinatorial platform for studying cancer pathogenesis and testing
      the efficacy of single or multi-drug therapeutics for cancer treatment.

PMID- 29378237
TI  - Increased mitochondrial turnover in the skeletal muscle of fasted, castrated mice
      is related to the magnitude of autophagy activation and muscle atrophy.
AB  - Androgen-deficiency promotes muscle atrophy in part by increasing autophagy
      mediated muscle protein breakdown during the fasted state, but factors
      contributing to this remain undefined. To identify novel factors, mice were
      subjected to sham or castration surgery. Seven-weeks post-surgery, mice were
      fasted overnight, refed for 30 min, and fasted another 4.5 h before sacrifice.
      BNIP3-mediated turnover of mitochondria was increased within the atrophied
      tibialis anterior (TA) of castrated mice and related to the magnitude of muscle
      atrophy and autophagy activation (i.e. decreased p62 protein content), thus
      linking turnover of potentially dysfunctional mitochondria with autophagy
      mediated atrophy. Autophagy induction was likely facilitated by AMPK activation
      as a stress survival mechanism since phosphorylation of AMPK (Thr172), as well as
      the pro survival kinases Akt (Thr308) and (ERK1/2 Thr202/Tyr204), were increased
      by castration. Together, these data identify a novel relationship between
      mitochondrial turnover in the fasted state with autophagy activation and muscle
      atrophy following androgen depletion.

PMID- 29378236
TI  - Partial growth hormone insensitivity and dysregulatory immune disease associated
      with de novo germline activating STAT3 mutations.
AB  - Germinal heterozygous activating STAT3 mutations represent a novel monogenic
      defect associated with multi-organ autoimmune disease and, in some cases, severe
      growth retardation. By using whole-exome sequencing, we identified two novel
      STAT3 mutations, p.E616del and p.C426R, in two unrelated pediatric patients with
      IGF-I deficiency and immune dysregulation. The functional analyses showed that
      both variants were gain-of-function (GOF), although they were not constitutively
      phosphorylated. They presented differences in their dephosphorylation kinetics
      and transcriptional activities under interleukin-6 stimulation. Both variants
      increased their transcriptional activities in response to growth hormone (GH)
      treatment. Nonetheless, STAT5b transcriptional activity was diminished in the
      presence of STAT3 GOF variants, suggesting a disruptive role of STAT3 GOF
      variants in the GH signaling pathway. This study highlights the broad clinical
      spectrum of patients presenting activating STAT3 mutations and explores the
      underlying molecular pathway responsible for this condition, suggesting that
      different mutations may drive increased activity by slightly different
      mechanisms.

PMID- 29378238
TI  - Loss of ATRX suppresses ATM dependent DNA damage repair by modulating H3K9me3 to
      enhance temozolomide sensitivity in glioma.
AB  - Mutations in ATRX constitute the most prevalent genetic abnormalities in gliomas.
      The presence of ATRX mutations in glioma serves as a marker of better prognosis
      with longer patient survival although the underlying mechanisms are poorly
      understood. In the present study, we found that ATRX biological function was
      significantly involved in DNA replication and repair. CRISPR/Cas9-mediated
      genetic inactivation of ATRX induced inhibition of cell proliferation, invasion
      and vasculogenic mimicry. In addition, temozolomide (TMZ) treatment induced
      greater DNA damage and apoptotic changes in ATRX knockout glioma cells. Moreover,
      we confirmed that ATRX knockout resulted in a failure to trigger ATM
      phosphorylation and finally restrained the activation of downstream proteins of
      the ATM pathway. The ATM-associated DNA repair pathway was extensively
      compromised in ATRX knockout cells owing to decreased histone H3K9me3
      availability. Public databases also showed that patients with low ATRX expression
      exhibited preferable overall survival and profited more from TMZ treatment. These
      data suggest that ATRX is involved in DNA damage repair by regulating the ATM
      pathway and might serve as a prognostic maker in predicting TMZ chemosensitivity.

PMID- 29378239
TI  - BioMEMS for biosensors and closed-loop drug delivery.
AB  - The efficacy of pharmaceutical treatments can be greatly enhanced by
      physiological feedback from the patient using biosensors, though this is often
      invasive or infeasible. By adapting microelectromechanical systems (MEMS)
      technology to miniaturize such biosensors, previously inaccessible signals can be
      obtained, often from inside the patient. This is enabled by the device's
      extremely small footprint which minimizes both power consumption and implantation
      trauma, as well as the transport time for chemical analytes, in turn decreasing
      the sensor's response time. MEMS fabrication also allows mass production which
      can be easily scaled without sacrificing its high reproducibility and
      reliability, and allows seamless integration with control circuitry and telemetry
      which is already produced using the same materials and fabrication steps. By
      integrating these systems with drug delivery devices, many of which are also MEMS
      based, closed loop drug delivery can be achieved. This paper surveys the types of
      signal transduction devices available for biosensing-primarily electrochemical,
      optical, and mechanical-looking at their implementation via MEMS technology. The
      impact of MEMS technology on the challenges of biosensor development,
      particularly safety, power consumption, degradation, fouling, and foreign body
      response, are also discussed.

PMID- 29378241
TI  - A small set of differentially expressed genes was associated with two color
      morphs in natural populations of the pea aphid Acyrthosiphon pisum.
AB  - Color polymorphism is an ecologically important trait, which is related to local
      adaptation and ecological speciation. The pea aphid Acyrthosiphon pisum shows
      color polymorphism: the red and green color morphs where differences in
      ecological adaptation have been observed. Here, we measured genome-wide gene
      expression profiles of two color morphs in natural populations of A. pisum to
      explore the genetic basis of differentiated ecological adaptation. The results
      showed that only 32 genes were significantly differentially expressed between the
      two morphs, of which 18 had functional annotations. Among them, 13 genes were up
      regulated [e.g. genes encoding protoheme IX farnesyltransferase (LOC100570971),
      carotene dehydrogenase (tor) and V-type proton ATPase subunit B (LOC100169462)]
      and 5 genes were down-regulated in the red morph (e.g. genes encoding
      transcription factors and heat shock proteins). To assess the functional
      importance of these differentially expressed genes (DEGs), we selected three
      highly expressed DEGs (LOC100169462, LOC100570971 and tor) with functional
      annotations and analyzed their expression levels in the red morph under three low
      temperatures (1  degrees C, 4  degrees C, and 8  degrees C) for 24 h. These three
      DEGs showed an interesting expression response to the cold acclimating conditions
      which resulted in an obvious phenotypic change of the red individuals to be
      greenish variants. This study suggests a link between gene expressions and body
      color polymorphisms in the pea aphid and provides important clues for further
      studying molecular mechanisms of ecological adaptation in aphids.

PMID- 29378242
TI  - Identification of a novel mutation (Ala66Thr) of SRY gene causes XY pure gonadal
      dysgenesis by affecting DNA binding activity and nuclear import.
AB  - Sex-determining region of the Y chromosome (SRY) gene plays a crucial role in
      male sexual differentiation and development. Several mutations in the SRY gene
      have been reported in the high mobility group (HMG) box domain and can cause
      gonadal dysgenesis symptoms. In this study, we report that a novel missense
      mutation in the SRY gene, a G to A transition within the HMG box, causes the
      Ala66Thr amino acid substitution in a female patient presenting 46,XY karyotype
      with pure gonadal dysgenesis. The G to A base transition was not found in the SRY
      sequence after the screening of 100 normal males. Furthermore, Ala66Thr mutation
      drastically reduced the binding capacity of SRY to DNA sequences, whereas wild
      type SRY protein showed the normal binding capacity to DNA sequences in vitro. We
      also found that the mutant SRY protein was partly localized in cytoplasm, whereas
      wild-type SRY protein was strictly localized in cell nucleus. In addition, we
      analyzed the three-dimensional structure of SRY protein by homology modeling
      methods. In conclusion, we identified a novel SRY mutation in a 46,XY female
      patient with pure gonadal dysgenesis, demonstrating the importance of the
      Ala66Thr mutation in DNA binding activity and nuclear transport.

PMID- 29378240
TI  - Fluconazole non-susceptible breakthrough candidemia after prolonged low-dose
      prophylaxis: a prospective FUNGINOS study.
AB  - OBJECTIVES: Breakthrough candidemia (BTC) on fluconazole was associated with non
      susceptible Candida spp. and increased mortality. This nationwide FUNGINOS study
      analyzed clinical and mycological BTC characteristics. METHODS: A 3-year
      prospective study was conducted in 567 consecutive candidemias. Species
      identification and antifungal susceptibility testing (CLSI) were performed in the
      FUNGINOS reference laboratory. Data were analyzed according to STROBE criteria.
      RESULTS: 43/576 (8%) BTC occurred: 37/43 (86%) on fluconazole (28 prophylaxis,
      median 200 mg/day). 21% BTC vs. 23% non-BTC presented severe sepsis/septic shock.
      Overall mortality was 34% vs. 32%. BTC was associated with gastrointestinal
      mucositis (multivariate OR 5.25, 95%CI 2.23-12.40, p < 0.001) and graft-versus
      host-disease (6.25, 1.00-38.87, p = 0.05), immunosuppression (2.42, 1.03-5.68, p
      = 0.043), and parenteral nutrition (2.87, 1.44-5.71, p = 0.003). Non-albicans
      Candida were isolated in 58% BTC vs. 35% non-BTC (p = 0.005). 63% of 16 BTC
      occurring after 10-day fluconazole were non-susceptible (Candida glabrata,
      Candida krusei, Candida norvegensis) vs. 19% of 21 BTC (C. glabrata) following
      shorter exposure (7.10, 1.60-31.30, p = 0.007). Median fluconazole MIC was 4 mg/l
      vs. 0.25 mg/l (p < 0.001). Ten-day fluconazole exposure predicted non-susceptible
      BTC with 73% accuracy. CONCLUSIONS: Outcomes of BTC and non-BTC were similar.
      Fluconazole non-susceptible BTC occurred in three out of four cases after
      prolonged low-dose prophylaxis. This implies reassessment of prophylaxis duration
      and rapid de-escalation of empirical therapy in BTC after short fluconazole
      exposure.

PMID- 29378244
TI  - ATF3 is positively involved in particulate matter-induced airway inflammation in
      vitro and in vivo.
AB  - Airborne particulate matter (PM) has been reported to be associated with a wide
      range of respiratory disorders. However, the mechanisms underlying PM-induced
      airway inflammation remain largely unknown. Generally, ATF3 negatively regulates
      pro-inflammatory cytokines production in response to TLR4 signaling. Here we
      first showed ATF3 has promoting effects in PM-induced airway inflammation in
      vitro an in vivo. We demonstrated PM significantly upregulated ATF3 expression in
      HBE cells and in mouse lung tissues. ATF3 siRNA markedly inhibited, while ATF3
      recombinant over-expression plasmid significantly increased PM-induced IL-6
      expression in cultured HBE cells, and PM-induced IL-6, CXCL2 expression as well
      as neutrophil infiltration, mucus over-production in the lung of ATF3-/- mice
      were all notably reduced relative to the wild-type littermates. Furthermore, we
      showed ATF3 mediated PM-induced inflammatory cytokines expression partly through
      NF-kappaB and AP-1 pathways. Our data further elucidates the mechanisms
      underlying PM-induced airway inflammation, and indicates ATF3 may function as
      different role in response to different stimuli.

PMID- 29378245
TI  - Neuroglobin overexpression plays a pivotal role in neuroprotection through
      mitochondrial raft-like microdomains in neuroblastoma SK-N-BE2 cells.
AB  - Since stressing conditions induce a relocalization of endogenous human
      neuroglobin (NGB) to mitochondria, this research is aimed to evaluate the
      protective role of NGB overexpression against neurotoxic stimuli, through
      mitochondrial lipid raft-associated complexes. To this purpose, we built a
      neuronal model of oxidative stress by the use of human dopaminergic neuroblastoma
      cells, SK-N-BE2, stably overexpressing NGB by transfection and treated with 1
      methyl-4-phenylpyridinium ion (MPP+). We preliminary observed the redistribution
      of NGB to mitochondria following MPP+ treatment. The analysis of mitochondrial
      raft-like microdomains revealed that, following MPP+ treatment, NGB translocated
      to raft fractions (Triton X-100-insoluble), where it interacts with ganglioside
      GD3. Interestingly, the administration of agents capable of perturbating
      microdomain before MPP+ treatment, significantly affected viability in SK-N-BE2
      NGB cells. The overexpression of NGB was able to abrogate the mitochondrial
      injuries on complex IV activity or mitochondrial morphology induced by MPP+
      administration. The protective action of NGB on mitochondria only takes place if
      the mitochondrial lipid(s) rafts-like microdomains are intact, indeed NGB fails
      to protect complex IV activity when purified mitochondria were treated with the
      lipid rafts disruptor methyl-beta-cyclodextrin. Thus, our unique in vitro model
      of stably transfected cells overexpressing endogenous NGB allowed us to suggest
      that the role in neuroprotection played by NGB is reliable only through
      interaction with mitochondrial lipid raft-associated complexes.

PMID- 29378243
TI  - Alterations in the nigrostriatal dopamine system after acute systemic PhIP
      exposure.
AB  - Heterocyclic amines (HCAs) are primarily formed during cooking of meat at high
      temperature. HCAs have been extensively studied as mutagens and possible
      carcinogens. Emerging data suggest that HCAs are neurotoxic and may be relevant
      to Parkinson's disease (PD) etiology. However, the majority of HCAs have not been
      evaluated for in vivo neurotoxicity. Here, we investigated acute in vivo
      neurotoxicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). PhIP is
      the most prevalent genotoxin in many types of meats. Adult, male Sprague-Dawley
      rats were subjected to acute, systemic PhIP at doses and time-points that have
      been extensively utilized in cancer studies (100 and 200 mg/kg for 8, 24 h) and
      evaluated for changes in dopaminergic, serotoninergic, GABAergic, and
      glutamatergic neurotransmission. PhIP exposure resulted in decreased striatal
      dopamine metabolite levels and dopamine turnover in the absence of changes to
      vesicular monoamine transporter 2 levels; other neurotransmitter systems were
      unaffected. Quantification of intracellular nitrotyrosine revealed higher levels
      of oxidative damage in dopaminergic neurons in the substantia nigra after PhIP
      exposure, while other neuronal populations were less sensitive. These changes
      occurred in the absence of an overt lesion to the nigrostriatal dopamine system.
      Collectively, our study suggests that acute PhIP treatment in vivo targets the
      nigrostriatal dopaminergic system and that PhIP should be further examined in
      chronic, low-dose studies for PD relevance.

PMID- 29378246
TI  - Phenotypes and endotypes of food allergy: A path to better understanding the
      pathogenesis and prognosis of food allergy.

PMID- 29378247
TI  - Convergent herbivory on conifers by Choristoneura moths after boreal forest
      formation.
AB  - Mitogenomes are useful markers for phylogenetic studies across a range of
      taxonomic levels. Here, we focus on mitogenome variation across the tortricid
      moth genus Choristoneura and particularly the spruce budworm (Choristoneura
      fumiferana) species complex, a notorious pest group of North American conifer
      forests. Phylogenetic relationships of Tortricidae, representing two subfamilies,
      four tribes and nine genera, were analyzed using 21 mitogenomes. These included
      six newly-sequenced mitogenomes for species in the spruce budworm complex plus
      three additional Choristoneura species and 12 previously published mitogenomes
      from other tortricids and one from the Cossidae. We evaluated the phylogenetic
      informativeness of the mitogenomes and reconstructed a time-calibrated tree with
      fossil and secondary calibrations. We found that tortricid mitogenomes had
      conserved protein and ribosomal regions, and analysis of all protein-coding plus
      ribosomal genes together provided an efficient marker at any taxonomic rank. The
      time-calibrated phylogeny showed evolutionary convergence of conifer feeding
      within Choristoneura, with two independent lineages, the Nearctic spruce budworm
      complex and the Palearctic species Choristoneura murinana, both shifting onto
      conifers about 11 million years ago from angiosperms. These two host-plant shifts
      both occurred after the formation of boreal forest in the late Miocene. Haplotype
      diversification within the spruce budworm complex occurred in the last 4 million
      years, and is probably linked to the initial cooling cycles of the Northern
      Hemisphere in the Pliocene.

PMID- 29378248
TI  - Effect of dietary nitrate levels on nitrate fluxes in rat skeletal muscle and
      liver.
AB  - Rodent skeletal muscle has high levels of nitrate ions and this endogenous
      nitrate reservoir can supply nitrite/nitric oxide (NO) for functional hyperemia
      and/or for other physiological processes in muscle during exercise. Mice with a
      NOS1 knockout have markedly reduced muscle nitrate levels, suggesting NO
      production by NOS and its reaction with oxymyoglobin as a source of nitrate.
      However, oxygen levels are normally low in most internal organs, which raises the
      possibility that nitrate-derived NO pathway is physiologically important even at
      "normoxia", and muscle nitrate reservoir is the main endogenous NO backup when
      exogeneous (dietary) nitrate intake is low. Using dietary nitrate manipulations,
      we explore the importance of diet for maintaining and renewal of muscle nitrate
      reservoir and its levels in other tissues. We found that skeletal muscle nitrate
      is extensively used when nitrate in diet is low. One week of nitrate starvation
      leads to dramatic nitrate depletion in skeletal muscle and a substantial decrease
      in liver. Nitrate depleted from skeletal muscle during starvation is quickly
      recovered from new dietary sources, with an unexpected significant "overload"
      compared with animals not subjected to nitrate starvation. Our results suggest
      the importance of dietary nitrate for nitrate reserves in muscle and in other
      tissues, when compared with endogenous NOS-derived sources. This requires an
      active transport mechanism for sequestering nitrate into cells, stimulated by
      lack of dietary nitrate or other enzymatic changes. These results confirm the
      hypothesis that muscle is a major storage site for nitrate in mammals.

PMID- 29378249
TI  - Contrasting effects of low versus high ascorbate doses on blood pressure
      responses to oral nitrite in L-NAME-induced hypertension.
AB  - Nitrite reduces blood pressure (BP) in both clinical and experimental
      hypertension. This effect is attributable to the formation of nitric oxide (NO)
      and other NO-related species, which may be improved by ascorbate or other
      antioxidants. However, the BP responses to oral nitrite result, at least in part,
      of increased gastric S-nitrosothiol formation. This study tested the hypothesis
      that ascorbate may destroy S-nitrosothiols and therefore not all doses of
      ascorbate enhance the BP responses to oral nitrite. We assessed the BP responses
      to oral sodim nitrite (0.2 mmol/kg) in L-NAME hypertensive rats pretreated with
      ascorbate (0, 0.02, 0.2, or 2 mmol/kg). Plasma and gastric wall concentrations of
      nitrite and nitroso compounds concentrations were determined using an ozone-based
      reductive chemiluminescence assay. Nitrate concentrations were determined using
      the Griess reaction. Free thiol concentrations were determined by a colorimetric
      assay. The BP responses to nitrite exhibited a bell-shape profile as they were
      not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and
      the 2 mmol/kg dose attenuated BP responses. In parallel with BP responses,
      nitrite-induced increases in plasma nitrite and RSNO species were not modified by
      ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg
      dose attenuated them. Similar experiments were carried out with an equimolar dose
      of S-nitrosogluthathione. Ascorbate dose-dependently impaired the BP responses to
      S-nitrosogluthathione, and the corresponding increases in plasma RSNO, but not in
      plasma nitrite concentrations. This is the first study to show that while
      ascorbate dose-dependently impairs the BP responses to oral S
      nitrosogluthathione, there are contrasting effects when low versus high ascorbate
      doses are compared with respect to its effects on the blood pressure responses to
      oral nitrite administration. Our findings may have special implications to
      patients taking ascorbate, as high doses of this vitamin may impair protective
      mechanisms associated with nitrite or nitrate from dietary sources.

PMID- 29378250
TI  - Accelerating clinical development timelines.

PMID- 29378251
TI  - CROs and CNS research: challenges and trends.

PMID- 29378252
TI  - Gut Microbiota, Hypertension and Chronic kidney Disease: recent advances.
AB  - A large number of different microbial species populates intestine. Extensive
      research has studied the entire microbial population and their genes (microbiome)
      by using metagenomics, metatranscriptomics and metabolomic analysis. Studies
      suggest that the imbalances of the microbial community causes alterations in the
      intestinal homeostasis, leading to repercussions on other systems: metabolic,
      nervous, cardiovascular, immune. These studies have also shown that alterations
      in the structure and function of the gut microbiota play a key role in the
      pathogenesis and complications of Hypertension (HTN) and Chronic Kidney Disease
      (CKD). Increased blood pressure (BP) and CKD are two leading risk factors for
      cardiovascular disease and their treatment represents a challenge for the
      clinicians. In this Review, we discuss mechanisms whereby gut microbiota (GM) and
      its metabolites act on downstream cellular targets to contribute to the
      pathogenesis of HTN and CKD, and potential therapeutic implications.

PMID- 29378253
TI  - Evaluation and optimized selection of supersaturating drug delivery systems of
      posaconazole (BCS class 2b) in the gastrointestinal simulator (GIS): An in vitro
      in silico-in vivo approach.
AB  - Supersaturating drug delivery systems (SDDS) have been put forward in the recent
      decades in order to circumvent the issue of low aqueous solubility. Prior to the
      start of clinical trials, these enabling formulations should be adequately
      explored in in vitro/in silico studies in order to understand their in vivo
      performance and to select the most appropriate and effective formulation in terms
      of oral bioavailability and therapeutic outcome. The purpose of this work was to
      evaluate the in vivo performance of four different oral formulations of
      posaconazole (categorized as a biopharmaceutics classification system (BCS) class
      2b compound) based on the in vitro concentrations in the gastrointestinal
      simulator (GIS), coupled with an in silico pharmacokinetic model to predict their
      systemic profiles. Recently published intraluminal and systemic concentrations of
      posaconazole for these formulations served as a reference to validate the in
      vitro and in silico results. Additionally, the morphology of the formed
      precipitate of posaconazole was visualized and characterized by optical
      microscopy studies and thermal analysis. This multidisciplinary work demonstrates
      an in vitro-in silico-in vivo approach that provides a scientific basis for
      screening SDDS by a user-friendly formulation predictive dissolution (fPD) device
      in order to rank these formulations towards their in vivo performance.

PMID- 29378255
TI  - Effect of an oral health education program based on the use of quantitative light
      induced fluorescence technology in Uzbekistan adolescents.
AB  - OBJECTIVES: The aim of this study was to determine whether an oral health
      education program using a Qscan device based on quantitative light-induced
      fluorescence (QLF) technology could improve the oral hygiene status and oral
      health literacy of adolescents. MATERIALS AND METHODS: One hundred adolescents
      aged 14-16 years attending a school in Tashkent city were included in this study.
      The participants were assigned to the following two groups using permuted block
      randomization technique: (i) control group (traditional learning) and (ii)
      experimental group (Qscan device-based learning). The participants included in
      the experimental group received additional education and training on dental
      plaque removal using the Qscan device. The accumulated levels of plaque were
      assessed in all participants, who also completed questionnaires about their oral
      health status, oral health knowledge, attitude, and behavior during an 8-week
      period. RESULTS: There were statistically significant improvements in the
      experimental group compared to the control group in the plaque index (0.46 vs
      0.07, p < .05), oral health knowledge (19.4 vs 28.8, p < .05), attitude (16.7 vs
      20.2, p < .05), and behavior (19.9 vs 30.5, p < .05). CONCLUSIONS: This study has
      demonstrated that an oral health education program based on the use of QLF
      technology could be useful for improving the oral hygiene status and oral health
      literacy of adolescents in Uzbekistan.

PMID- 29378254
TI  - Toxicokinetics of the neonicotinoid insecticide imidacloprid in rainbow trout
      (Oncorhynchus mykiss).
AB  - Studies were conducted to determine the distribution and elimination of
      imidacloprid (IMI) in rainbow trout. Animals were injected with a low (47.6
      MUg/kg), medium (117.5 MUg/kg) or high (232.7 MUg/kg) dose directly into the
      bloodstream and allowed to depurate. The fish were then sampled to characterize
      the loss of IMI from plasma and its appearance in expired water (all dose groups)
      and urine (medium dose only). In vitro biotransformation of IMI was evaluated
      using trout liver S9 fractions. Mean total clearance (CLT) values determined by
      non-compartmental analysis of plasma time-course data were 21.8, 27.0 and 19.5
      mL/h/kg for the low, medium and high dose groups, respectively. Estimated half
      lives for the same groups were 67.0, 68.4 and 68.1 h, while fitted values for the
      steady-state volume of distribution (VSS) were 1.72, 2.23 and 1.81 L/kg.
      Branchial elimination rates were much lower than expected, suggesting that IMI is
      highly bound in blood. Renal clearance rates were greater than measured rates of
      branchial clearance (60% of CLT in the medium dose group), possibly indicating a
      role for renal membrane transporters. There was no evidence for hepatic
      biotransformation of IMI. Collectively, these findings suggest that IMI would
      accumulate in trout in continuous waterborne exposures.

PMID- 29378256
TI  - Curcumin-mediated Photodynamic Therapy for the treatment of oral infections-A
      review.
AB  - BACKGROUND: Recent evidences show the promising applications of Curcumin (CUR)
      against different diseases, including some of the main oral pathologies. The
      objective of this review paper was to catalog articles that investigated the
      photodynamic effect of CUR for oral diseases in the last 15 years. METHODS: The
      establishment of defined criteria for data collection was proposed and a total of
      173 articles were identified, but only 26 were eligible for full text reading.
      Their main findings were critically reviewed to provide a state-of-the-art
      overview of the use of CUR in Dentistry. RESULTS: Antimicrobial potential of CUR
      was the subject of the majority of the articles. CUR showed great potential for
      photodynamic action against oral bacteria, fungi, and strains resistant to
      conventional drugs. Some authors indicated the efficacy of CUR-mediated
      Photodynamic Therapy to reduce tumor cells while others observed low cytotoxicity
      in mammalian cells and healthy oral mucosa. However, CUR solubility and stability
      is still a problem for the photodynamic technique, and to overcome these
      drawbacks, biocompatible vehicles need to be better explored. CONCLUSIONS:
      Investigations have used different CUR concentrations and formulations, as well
      as different light parameters. This fact, together with the lack of in vivo
      studies, clearly shows that clinical protocols have not been established yet.
      Investigations are necessary in order to establish the best concentrations and
      safe vehicles to be used for this technique.

PMID- 29378257
TI  - Neprilysin Inhibition: What We Know and What We Don't Know.

PMID- 29378258
TI  - Pregnancy outcomes after maternal use of thiocolchicoside: A case series.
AB  - OBJECTIVE: The 2014 report by European Medicines Agency (EMA) restricted the use
      of thiocolchicoside for all reproductive-age women. In this study, we aim to
      expand the systematically-collected human data and discuss it within the frame
      provided by this report. METHODS: We identified and evaluated the outcomes of 48
      prospectively recorded pregnancies referred to Terafar (Teratology Information
      Service, Izmir, Turkey). RESULTS: Of 42 pregnancies with first-trimester exposure
      and known outcomes, 31 resulted in live births, four in miscarriage and seven
      ended with elective terminations. There were 26 normal outcomes, two major and
      three minor congenital malformations among the live births. CONCLUSIONS: Despite
      a number of limitations, our results and previous case series collectively
      strengthen the view that thiocolchicoside is unlikely to be a major teratogen.
      EMA's 2014 report should be revised to reflect this finding, while current
      restrictions on use should continue until more detailed safety information is
      available.

PMID- 29378259
TI  - Delay in Adjuvant Chemotherapy and Survival Advantage in Stage III Colon Cancer.
AB  - BACKGROUND: Adjuvant chemotherapy after resection is the standard of care for
      stage III colon cancer, yet many patients omit chemotherapy. We aimed to describe
      the impact of delayed chemotherapy on overall survival across multiple time
      points. STUDY DESIGN: The 2006 to 2014 National Cancer Data Base (NCDB) was
      queried for patients with single primary stage III adenocarcinoma of the colon.
      Patients were grouped by receipt and timing of chemotherapy from resection date:
      chemotherapy omitted, <6 weeks, 6 to 8 weeks, 8 to 12 weeks, 12 to 24 weeks, and
      >24 weeks. Subgroup analyses were performed for those with comorbidities and
      those who had postoperative complications. Overall survival was compared using
      Cox proportional hazard modeling, adjusting for patient, tumor, and facility
      characteristics. RESULTS: In total, 72,057 patients were included; 20,807 omitted
      chemotherapy, 22,705 received it at <6 weeks, 15,412 between 6 and 8 weeks, 9,049
      between 8 and 12 weeks, 3,595 between 12 and 24 weeks, and 489 at >24 weeks after
      resection. Compared with patients who omitted chemotherapy, patients who received
      chemotherapy at <6 weeks (hazard ratio [HR] 0.44), 6 to 8 weeks (HR 0.45), 8 to
      12 weeks (HR 0.52), 12 to 24 weeks (HR 0.61), and >24 weeks (HR 0.68) had
      superior overall survival (p < 0.001). This survival benefit was preserved across
      subgroups (p < 0.001). CONCLUSIONS: After resection of stage III colon cancer,
      patients should receive adjuvant chemotherapy within 6 to 8 weeks for maximal
      benefit. However, chemotherapy should be offered to patients who are outside the
      optimal window, who have significant comorbidities, or who have had a
      complication more than 24 weeks from resection to improve the overall survival
      compared with omitting chemotherapy.

PMID- 29378260
TI  - Kinetic properties analysis of beta-mannanase from Klebsiella oxytoca KUB-CW2-3
      expressed in Escherichia coli.
AB  - Endo-1,4-beta-mannanase is an enzyme that can catalyze the random hydrolysis of
      beta-1,4-mannosidic linkages in the main chain of mannans, glucomannans and
      galactomannans and offers many applications in different biotechnology
      industries. Purification and kinetic properties of the endo-1,4-beta-mannanase
      from recombinant Escherichia coli strain KMAN-3 were examined. Recombinant beta
      mannanase (KMAN-3) was purified 50.5 fold using Ni-NTA Agarose resin and specific
      activity of 11900 U/mg protein was obtained. Purified KMAN-3 showed a single band
      on SDS-PAGE with a molecular weight of 43 kDa. Km and Vmax values of KMAN-3 on
      ivory nut mannan, locust bean gum, defatted copra meal and konjac glucomannan
      were 243, 3.83 * 105 37 and 2.13 * 106 mg ml-1 and 2940, 61,100, 3930 and 1.56 *
      1010 mg-1, respectively. Carboxymethyl cellulose was not digested by KMAN-3.

PMID- 29378261
TI  - Improving the quality of a recombinant rabbit monoclonal antibody against PLXDC2
      by optimizing transient expression conditions and purification method.
AB  - Rabbit monoclonal antibodies (mAbs) have many advantages over mouse antibodies in
      biological research and diagnostics applications because they exhibit high
      affinity and specificity. However, the methods of recombinant rabbit mAb
      production have not been optimized to the same extent as techniques used to
      produce mouse and human mAbs. In this study, we sought to optimize the production
      of a recombinant rabbit mAb against human plexin domain containing protein 2
      (PLXDC2), a known cell surface antigen, by culturing HEK293-6E cells transfected
      with antibody-encoding genes at two different temperatures and by purifying the
      end-product by three different chromatography methods. The quality and function
      of purified antibody preparations were checked by electrophoresis and western
      blot analysis. The secreted rabbit mAb produced by a combination of culturing at
      32  degrees C, purification by ammonium sulfate fractionation, and
      diethylaminoethyl resin (DEAE) ion exchange chromatography was of high quality.
      In contrast, the antibody produced by the cells grown at 37  degrees C for 6 days
      after transfection and purified by Protein A/G affinity method was low quality.
      Hypothermic conditions during production reduced protein heterogeneity probably
      by favorably affecting the levels of glycosylation and aggregation. In
      particular, according to western blotting data, CIMmultus DEAE chromatography
      that utilizes monolithic columns not only excluded inferior charge variants
      resulting from nonspecific reactions but also yielded rabbit mAb that was of
      better quality than commercially available rabbit polyclonal antibodies. The
      combination of techniques suggested by us may be a general approach to enhance
      product quality of rabbit mAbs produced by transient expression systems.

PMID- 29378262
TI  - A new focal model resembling features of cortical pathology of the progressive
      forms of multiple sclerosis: Influence of innate immunity.
AB  - Multiple sclerosis (MS) is an inflammatory and demyelinating disease of unknown
      aetiology that causes neurological disabilities in young adults. MS displays
      different clinical patterns, including recurrent episodes with remission periods
      ("relapsing-remitting MS" (RRMS)), which can progress over several years to a
      secondary progressive form (SPMS). However, 10% of patients display persistent
      progression at the onset of disease ("primary progressive MS" (PPMS)). Currently,
      no specific therapeutic agents are available for the progressive forms, mainly
      because the underlying pathogenic mechanisms are not clear and because no animal
      models have been specifically developed for these forms. The development of MS
      animal models is required to clarify the pathological mechanisms and to test
      novel therapeutic agents. In the present work, we overexpressed interleukin 1
      beta (IL-1beta) in the cortex to develop an animal model reflecting the main
      pathological hallmarks of MS. The treated animals presented with
      neuroinflammation, demyelination, glial activation, and neurodegeneration along
      with cognitive symptoms and MRI images consistent with MS pathology. We also
      demonstrated the presence of meningeal inflammation close to cortical lesions,
      with characteristics similar to those described in MS patients. Systemic pro
      inflammatory stimulation caused a flare-up of the cortical lesions and
      behavioural symptoms, including impairment of working memory and the appearance
      of anxiety-like symptoms. Our work demonstrated induced cortical lesions,
      reflecting the main histopathological hallmarks and cognitive impairments
      characterizing the cortical pathology described in MS patients with progressive
      forms of the disease.

PMID- 29378263
TI  - Interaction between microbiome and host genetics in psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, seen in
      combination with psoriasis. Both genetic and environmental factors are
      responsible for the development of PsA, however little is known about the
      different weight of these two distinctive components in the pathogenesis of the
      disease. Genomic variability in PsA is associated with the disease and/or some
      peculiar clinical phenotypes. Candidate genes involved are crucial in
      inflammation, immune system, and epithelial permeability. Moreover, the genesis
      and regulation of inflammation are influenced by the composition of the human
      intestinal microbiome that is able to modulate both mucosal and systemic immune
      system. It is possible that pro-inflammatory responses initiated in gut mucosa
      could contribute to the induction and progression of autoimmune conditions. Given
      such premises, the aim of this review is to summarize immune-mediated response
      and specific bacterial changes in the composition of fecal microbiota in PsA
      patients and to analyze the relationships between bacterial changes, immune
      system, and host genetic background.

PMID- 29378264
TI  - Molecular characterization of Rhodnius robustus specimens, potential vectors for
      Chagas disease in French Guiana, South America.
AB  - Insects of the genus Rhodnius are broadly involved in Chagas disease
      transmission. In French Guiana, where the disease remains a public health
      problem, R. robustus and R. pictipes are vectors, but so far few genetic analyses
      of these local species have been reported. Here, we explored three mitochondrial
      genes (Cytb, Lsu-rRNA, and ND1) and one nuclear gene (D2) in 49 adult specimens
      morphologically characterized as R. robustus. We analyzed genetic polymorphisms
      and haplotype distributions, and we built phylogenetic trees using the available
      GenBank sequences from R. robustus and related species. The molecular taxonomy
      analysis confirmed that 35 insects, closely related to Brazilian species and
      separated by a few mutations, truly belong to R. robustus; two others were
      attributed to the R. prolixus complex and for 12 no sequence was obtained. The
      geographical haplotype distribution indicates a likely geographical structuring
      and evidenced true differentiation between the two main urban centers, Cayenne
      and Saint-Laurent-du-Maroni.

PMID- 29378265
TI  - Whipple's disease mimicking an auto-inflammatory disease with myositis and soft
      tissue inflammation.

PMID- 29378266
TI  - Association of PD-L1 Expression with Tumor-Infiltrating Immune Cells and Mutation
      Burden in High-Grade Neuroendocrine Carcinoma of the Lung.
AB  - INTRODUCTION: The immune microenvironment of high-grade neuroendocrine carcinoma
      of the lung, including programmed death ligand 1 (PD-L1) expression, has not been
      well characterized. METHODS: On the basis of immunohistochemistry (IHC) results,
      PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs)
      was scored as follows: TC0 and IC0 were defined as PD-L1 expression less than 1%,
      TC1 and IC1 as at least 1% but less than 10%, TC2 and IC2 as 10% or more but less
      than 50%, and TC3 and IC3 as 50% or more. Phosphatase and tensin homolog (PTEN)
      IHC was scored as either lost or retained expression. The Ion AmpliSeq
      Comprehensive Cancer Panel (ThermoFisher Scientific, Waltham, MA) was used to
      identify mutations in all coding exons of 409 cancer-related genes. RESULTS: A
      total of 192 patients with large cell neuroendocrine carcinoma (LCNEC) (n = 72)
      and SCLC (n = 120) were studied. The prevalence of PD-L1 expression on TCs was
      15.1% (29 of 192). IC infiltration and PD-L1 expression on ICs were observed in
      34.4% of patients (66 of 192) and 31.3% of patients (60 of 192), respectively.
      The prevalence of IC infiltration and PD-L1 expression on IC were more strongly
      correlated with LCNEC than with SCLC (57.6% versus 23.3%, p < 0.01; 45.8% versus
      22.5%, p < 0.01) and high nonsynonymous mutations (p = 0.05 and .04). PTEN loss
      was found in 9.5% of patients (18 of 189) and showed no correlation with PD-L1
      expression. Progression-free survival was better in patients with IC infiltration
      than in those without IC infiltration (median 11.3 versus 6.8 months [p < 0.01])
      and in patients with PD-L1 expression of IC1/2/3 than in those with expression of
      IC0 (median 11.3 versus 7.0 months [p = 0.03]). CONCLUSION: These findings
      suggest that the PD-1/PD-L1 pathway is activated in the microenvironment of
      pulmonary high-grade neuroendocrine carcinoma and correlated with a higher
      mutation burden.

PMID- 29378267
TI  - Safety of Combined PD-1 Pathway Inhibition and Intracranial Radiation Therapy in
      Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: Intracranial metastases are a common cause of morbidity and
      mortality in patients with advanced NSCLC, and are frequently managed with
      radiation therapy (RT). The safety of cranial RT in the setting of treatment with
      immune checkpoint inhibitors (ICIs) has not been established. METHODS: We
      identified patients with advanced NSCLC with brain metastases who received
      cranial RT and were treated with or without programmed cell death 1/programmed
      death ligand 1 inhibitors between August 2013 and September 2016. RT-related
      adverse events (AEs) were retrospectively evaluated and analyzed according to ICI
      treatment status, cranial RT type, and timing of RT with respect to ICI. RESULTS:
      Of 163 patients, 50 (31%) received ICIs, whereas 113 (69%) were ICI naive.
      Overall, 94 (58%), 28 (17%), and 101 (62%) patients received stereotactic
      radiosurgery, partial brain irradiation, and/or whole brain RT, respectively.
      Fifty percent of patients received more than one radiation course. We observed no
      significant difference in rates of all-grade AEs and grade 3 or higher AEs
      between the ICI-naive and ICI-treated patients across different cranial RT types
      (grade >=3 AEs in 8% of ICI-naive patients versus in 9% of ICI-treated patients
      for stereotactic radiosurgery [p = 1.00] and in 8% of ICI-naive patients versus
      in 10% of ICI-treated patients for whole brain RT [p = 0.71]). Additionally,
      there was no difference in AE rates on the basis of timing of ICI administration
      with respect to RT. CONCLUSIONS: Treatment with an ICI and cranial RT was not
      associated with a significant increase in RT-related AEs, suggesting that use of
      programmed cell death 1/programmed death ligand 1 inhibitors in patients
      receiving cranial RT may have an acceptable safety profile. Nonetheless,
      additional studies are needed to validate this approach.

PMID- 29378268
TI  - Rural-urban differences in human papillomavirus knowledge and awareness among US
      adults.
AB  - Rural residents of the United States have higher HPV-associated cancer incidence
      and mortality, and suboptimal HPV vaccine uptake compared to urban residents.
      This study aimed to assess differences in knowledge and awareness of HPV, the HPV
      vaccine, and HPV-associated cancers among rural and urban residents. We analyzed
      data from the Health Information National Trends Survey 2013-2017 on 10,147
      respondents ages >=18 years. Multivariable logistic regression analyses compared
      urban/rural differences in knowledge and awareness of HPV, associated cancers,
      and HPV vaccine. Models were adjusted for sex, age, race/ethnicity, education,
      household income, census region, health insurance, regular provider, internet
      use, and personal history of cancer. Overall, 67.2% and 65.8% of urban residents
      were aware of HPV and HPV vaccine, respectively, compared to only 55.8% and 58.6%
      of rural residents. Adjusted models illustrated that compared to urban residents,
      rural residents were less likely to be aware of HPV (OR = 0.68, 95% CI = 0.53
      0.86) and HPV vaccine (OR = 0.78, 95% CI = 0.63-0.97). Among those who were aware
      of HPV, rural residents were less likely to know that HPV causes cervical cancer
      (OR = 0.62, 95% CI = 0.46-0.84) and that HPV can be transmitted through sexual
      contact (OR = 0.72, 95% CI = 0.56-0.94). No significant differences between rural
      and urban residents were noted for knowledge that HPV is transmitted sexually and
      that it causes oral, anal, and penile cancers. This study highlights significant
      rural health disparities in knowledge and awareness of HPV and the HPV vaccine
      compared to urban counterparts.

PMID- 29378269
TI  - Internet little cigar and cigarillo vendors: Surveillance of sales and marketing
      practices via website content analysis.
AB  - INTRODUCTION: Cigar sales have nearly doubled as cigarette sales have dropped,
      and large cigars have been replaced by little cigars and cigarillos (LCCs). Many
      LCCs are flavored, are perceived as less harmful than cigarettes, and have become
      increasingly available from e-commerce sources. We conducted surveillance of the
      online retail environment in 2013 and 2014 for LCCs in order to describe
      characteristics of Internet tobacco vendors selling LCCs and their sales and
      marketing practices, youth access practices, and their practices in relation to
      cigarette and other tobacco product sales. METHODS: In 2013, we identified and
      manually screened 32,446 websites, yielding 500 unique Internet LCC vendors. In
      2014, we identified 511 vendors selling LCCs from a list of 31,239 manually
      screened websites. We then selected 249 in 2013 and 263 in 2014 for content
      analysis focusing on six domains including demographics, youth access, payment
      and delivery, products for sale, promotions and claims, and prices. RESULTS: Just
      over half of vendors in both years were located solely in the U.S. with 70.1% of
      those selling flavored LCCs in 2013 and 76.1% in 2014. Nearly half only used
      proven ineffective age verification strategies and another 10% made no attempts
      to verify age at all. Most vendors accepted credit cards and advertised using the
      United States Postal Service. Half of vendors featured a variety of health
      warnings and most featured promotions. CONCLUSIONS: Federal bans on flavored
      cigarettes and restrictions on age verification, payment, and shipping for
      Internet tobacco sales should be extended to include LCCs.

PMID- 29378270
TI  - d-Ribose induced glycoxidative insult to hemoglobin protein: An approach to spot
      its structural perturbations.
AB  - Glycation of biological macromolecule leads to the establishment of advanced
      glycation end products (AGEs) having implications in metabolic disorders. d
      ribose appears to be the most reactive among the naturally occurring sugars and
      contribute significantly to the glycation reactions in vivo, however, no report
      have been published yet to discuss d-ribose induced glycation of hemoglobin (Hb).
      Therefore, the present study was designed to investigate d-ribose induced
      glycoxidative damage to Hb protein. Briefly, the commercially available Hb was
      glycated with d-ribose for varying time intervals. The structural perturbation
      induced in glycated Hb (GHb) was confirmed by biophysical techniques viz., UV
      visible, fluorescence spectroscopy, circular dichroism, Fourier transform infra
      red spectroscopy, dynamic light scattering, MALDIthermal denaturation by UV
      visible spectrophotometer and DSC. Biophysical techniques confirm the secondary
      and tertiary structural perturbation in GHb as compared to native Hb. The values
      of carbonyl content, hydroxy methyl furfural, thiobarbituric acid reactive
      substance and nitro blue tetrazolium were found to be increased and free lysine
      and free arginine content were decreased in the GHb due to structural change.
      Thus, results of this study have established that glycation with d-ribose lead to
      the structural changes in the native Hb which might play an important role in
      pathophysiology metabolic diseases.

PMID- 29378271
TI  - A new tactics for the detection of S. aureus via paper based geno-interface
      incorporated with graphene nano dots and zeolites.
AB  - Staphylococcus aureus (S. aureus) is a pathogenic bacteria which causes
      infectious diseases and food poisoning. Current diagnostic methods for infectious
      disease require sophisticated instruments, long analysis time and expensive
      reagents which restrict their application in resource-limited settings.
      Electrochemical paper based analytical device (EPAD) was developed by integrating
      graphene nano dots (GNDs) and zeolite (Zeo) using specific DNA probe. The
      ssDNA/GNDs-Zeo modified paper based analytical device (PAD) was characterized
      using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The
      genosensor was optimized at pH7.4 and incubation temperature of 30 degrees C. A
      linear current response with respect to target DNA concentrations was obtained.
      The limit of detection (LOD) of the proposed sensor was found out to be 0.1nM.
      The specificity was confirmed by introducing non-complimentary target DNA to
      ssDNA/GNDs-Zeo modified PAD. The suitability of the proposed EPAD genosensor was
      demonstrated with fruit juice samples mixed with S. aureus. The proposed EPAD
      genosensor is a low cost, highly specific, easy to fabricate diagnostic device
      for detection of S. aureus bacteria which requires very low sample volume and
      minimum analysis time of 10s.

PMID- 29378272
TI  - Fabrication and characterization of dual acting oleyl chitosan functionalised
      iron oxide/gold hybrid nanoparticles for MRI and CT imaging.
AB  - Bionanocomposites fabricated using metal nanoparticles serve a wide range of
      biomedical applications viz., site targeted drug delivery, imaging etc.
      Theranostics emerge as an important field of science, which focuses on the use of
      single entity for both disease diagnosis and treatment. The present work aimed at
      designing a multifunctional nanocomposite comprising of iron/gold hybrid
      nanoparticles, coated with oleyl chitosan and conjugated with methotrexate. The
      HR-TEM images revealed the spherical nature of the composite, while it's nontoxic
      and biocompatible property was proved by the MTT assay in NIH 3T3 cells and
      hemolysis assay. Though the VSM results exhibited the magnetic property, the MRI
      phantom images and X-ray contrast images demonstrated the potential of the
      composite to be used as contrast agent. Thus the prepared nanocomposite possess
      good cytocompatibility, magnetic property and also high X-ray attenuation,
      wherein it could serve as a novel platform for both MRI and CT diagnosis, as well
      as drug conjugation could aid in targeted drug delivery.

PMID- 29378273
TI  - pH and near-infrared active; chitosan-coated halloysite nanotubes loaded with
      curcumin-Au hybrid nanoparticles for cancer drug delivery.
AB  - In this work, we propose biofriendly in-situ preparation method of Au NPs
      (hexagonal and rod-shape structures) in the lumen as well as the surface cage of
      biocompatible halloysite nanotubes (HNTs) using curcumin (CUR) as anticancer drug
      and subsequently coating with bio-adhesive chitosan (CS) as a polysaccharide. The
      formation of Au NPs and their interactions with CUR and CS exist in the HNTs has
      been characterized by FTIR, XRD, XPS, STEM techniques. Interestingly, Au NPs
      showed longitudinal plasmon resonance bands at 760 and 980 nm that indicate the
      near-infrared (NIR) responsive property of hybrid nanoparticles. Rod shape and
      hexagonal structures of Au NPs were produced as confirmed by TEM images. The
      loading efficiency of CUR was found as much as 12%. Importantly, more CUR release
      was achieved under acidic conditions (pH 5.5) than basic conditions (pH 7.4). The
      anticancer potential of HNT hybrid nanoparticles on MCF-7 cancer cells was
      studied and showed efficient anticancer activity under intracellular tumor cell
      environment (pH 5.5) than extracellular conditions (pH 7.4). Moreover, the
      developed HNT hybrid nanoparticles consisting of Au NPs (NIR responsive property)
      and pH-responsive CUR release could make it suitable for cancer cell-targeted
      drug delivery platform with NIR-imaging.

PMID- 29378274
TI  - Nature of phase transitions of waxy maize starch in water-ionic liquid mixtures.
AB  - The nature of phase transitions of waxy maize starch heated in mixtures of water
      and ionic liquid (IL) was elucidated using a variety of analytical methods. The
      transition from a single endotherm to an exotherm followed by an endotherm, and
      then to a single exotherm was observed with the increasing concentration of IL.
      The results showed that at To of DSC phase transition no structural disruption
      had occurred. Except for the water/IL ratios of 1.5:1 and 1:1, there was
      considerable structural disruption of starch samples that were preheated to Tp or
      Tp2 of gelatinization transition. No residual structural order was observed at Tc
      of the gelatinization transition. An exothermic transition at water:IL ratios of
      3:1 and 2:1 was attributed to the interaction of ionic liquid and amorphous
      regions in starch. The molecular disassembly of starch granules during
      gelatinization in different water:IL mixtures proceeded to completion at
      different rates.

PMID- 29378275
TI  - Lanthanum (III) encapsulated chitosan-montmorillonite composite for the
      adsorptive removal of phosphate ions from aqueous solution.
AB  - In the present work, lanthanum (III) encapsulated chitosan-montmorillonite
      composite (La-CS-MMT) was prepared as an adsorbent for the effective removal of
      phosphate ions from aqueous solution. Characterization of the adsorbent using FT
      IR, XRD, SEM with EDX, TGA and DTA techniques were carried out. Batch adsorption
      experiments were carried out to optimize the effects of various operating
      parameters viz., shaking time, initial concentration of phosphate ions, dosage,
      competitor co-existing ions, pH and temperature. Phosphate ions adsorbed
      effectively on La-CS-MMT composite through hydrogen bonding and by outer-sphere
      complex formation mechanism. Freundlich isotherm model fit well with the
      equilibrium isotherm data. The experimental values of ?G degrees , ?S degrees 
      and ?H degrees  revealed that the nature of adsorption was feasible, spontaneous
      and exothermic. The kinetic study was well fitted with pseudo-second-order model.
      Regeneration study of the spent La-CS-MMT-P composite was carried out upto five
      cycles and found that about 70% of adsorption efficiency was retained.

PMID- 29378276
TI  - Biological macromolecules for ophthalmic drug delivery to treat ocular diseases.
AB  - Development of newer drug carrier systems by the researchers has resulted in
      numerous breakthroughs in the development and manufacturing of ocular products.
      The ocular bioavailability of drugs at the posterior segment of the eye is a
      challenging task in the present scenario. Naturally derived macromolecular
      carriers are widely used to increase the efficacy of ocular drugs. They provide
      enhanced corneal permeability and retention effect at the surface of cornea for a
      prolonged period of time. In this regimen the present review focuses towards the
      major ocular diseases and their prevalence and development of efficient drug
      carrier systems utilizing various naturally derived macromolecules for improved
      delivery of drugs to treat ocular diseases.

PMID- 29378277
TI  - Guargum and Eudragit (r) coated curcumin liquid solid tablets for colon specific
      drug delivery.
AB  - Colorectal cancer, also known as bowel cancer, is the uncontrolled cell growth in
      the colon or rectum (parts of the large intestine), or in the appendix. The colon
      specific drug delivery would alleviate the systemic side effects and would assure
      the safe therapy for colonic disorders with minimum dose and duration of therapy.
      The liquisolid technique refers to solubilisation of drug in a non-volatile
      solvent combined with inclusion of appropriate carrier and coating agent required
      for tableting. Colon specific degradation of natural polymer, guar gum and pH
      dependant degradative (pH-7) property of eudragit L100 restricts the delivery of
      curcumin in gastric and intestinal pH. Formulated curcumin liquisolid powder was
      evaluated for the micrometric properties, solubility and by differential thermal
      analysis, X ray powder diffraction and scanning electron microscopy. Curcumin
      loaded liquisolid tablet showed more anticancer activity against HCT-15 compared
      with free curcumin. Bioavailability study of the coated and uncoated liquisolid
      tablets were performed using Newzealand white rabbits. The present study
      concludes that liquisolid technique is a promising alternative for improving oral
      bioavailability and dissolution rate of water insoluble drug and coating
      liquisolid tablet with colon sensitive polymers showed site specific release of
      drug in the colon.

PMID- 29378278
TI  - Renal Pseudo-tumor Related to Renal Splenosis: Imaging Features.
AB  - OBJECTIVE: To report the case of a 29-year-old patient presenting with renal
      splenosis along with a complete review of literature on this condition. Splenosis
      is a frequent condition following abdominal trauma or splenectomy, described as
      splenic tissue that autotransplants into a heterotopic location. However, renal
      splenosis is rare and often mistaken with renal carcinoma. MATERIALS AND METHODS:
      The patient was initially referred to our department for a renal mass
      incidentally discovered on ultrasound. Further investigation included with
      computed tomography and magnetic resonance imaging. RESULTS: Imaging features
      revealed a well circumscribed solid renal mass, exhibiting an isosignal on T1-
      and T2-weighted sequences in comparison with the renal cortex. The mass exhibited
      a heterogeneous enhancement on the arterial and portal phases, homogeneous
      patterns during the delayed phases, and high signal intensity on diffusion
      weighted images. A partial nephrectomy was performed and pathological examination
      revealed the final diagnosis of renal splenosis. CONCLUSION: Imaging features
      alone do not provide a definitive diagnosis of splenosis but suggestive past
      history associated with imaging findings consistent with splenic tissue should
      lead to 99m technetium-sulfur colloid scanning or ferumoxid-enhanced MRI to avoid
      useless surgery.

PMID- 29378279
TI  - Hypoandrogenism is Prevalent in Males With Urethral Stricture Disease and is
      Associated with Longer Strictures.
AB  - OBJECTIVE: To assess the association of hypoandrogenism (HA) with urethral
      stricture disease in a series of patients undergoing urethroplasty at 2
      institutions. HA has recently been associated with increased urethral atrophy in
      artificial sphincter failures and decreased androgen receptors and periurethral
      vascularity. HA might be an etiologic factor in urethral stricture disease.
      METHODS: We reviewed the charts in 202 men with anterior urethral strictures
      between 2011 and 2017. We excluded patients with radiation-induced stricture,
      previous prostatectomy, previous urethroplasty, pelvic fracture-related
      strictures, or those on testosterone replacement. We defined HA by a total
      testosterone of less than 300 ng/dL. We used as age-matched cohort from a
      national database (National Health and Nutrition Examination Survey), as a
      reference. Stricture characteristics, such as length, location, and etiology were
      compared in HA and eugonadal groups. RESULTS: Of 202 men with anterior urethral
      strictures, we excluded 45. Of the remaining 157 patients, 115 (73%) had
      preoperative testosterone measurements. Overall, hypoandrogenism (HA) was found
      in 65 of 115 (57%) men in the urethral stricture group compared with 28% of age
      matched men in the national database. Mean stricture length in HA and eugonadal
      men was 7.2 cm and 4.8 cm, respectively (P = .02). CONCLUSION: HA may be more
      prevalent and associated with increased disease severity in men with anterior
      urethral strictures. The relationship between HA and stricture formation and its
      potential impact on therapeutic outcomes merit further prospective investigation.

PMID- 29378280
TI  - Speech Disfluency-dependent Amygdala Activity in Adults Who Stutter: Neuroimaging
      of Interpersonal Communication in MRI Scanner Environment.
AB  - Affective states, such as anticipatory anxiety, critically influence speech
      communication behavior in adults who stutter. However, there is currently little
      evidence regarding the involvement of the limbic system in speech disfluency
      during interpersonal communication. We designed this neuroimaging study and
      experimental procedure to sample neural activity during interpersonal
      communication between human participants, and to investigate the relationship
      between the amygdala activity and speech disfluency. Participants were required
      to engage in live communication with a stranger of the opposite sex in the MRI
      scanner environment. In the gaze condition, the stranger gazed at the participant
      without speaking, while in the live conversation condition, the stranger asked
      questions that the participant was required to answer. The stranger continued to
      gaze silently at the participant while the participant answered. Adults who
      stutter reported significantly higher discomfort than fluent controls during the
      experiment. Activity in the right amygdala, a key anatomical region in the limbic
      system involved in emotion, was significantly correlated with stuttering
      occurrences in adults who stutter. Right amygdala activity from pooled data of
      all participants also showed a significant correlation with discomfort level
      during the experiment. Activity in the prefrontal cortex, which forms emotion
      regulation neural circuitry with the amygdala, was decreased in adults who
      stutter than in fluent controls. This is the first study to demonstrate that
      amygdala activity during interpersonal communication is involved in disfluent
      speech in adults who stutter.

PMID- 29378281
TI  - Automatic Conflict Monitoring by Event-Related Potentials Could be used to
      Estimate Visual Acuity Levels.
AB  - Numerous studies have explored the physical attribute features or face
      perceptions in conflict processing, while complicate gradient conflicts were
      rarely discussed. The aim of the study was to discuss the relationship between
      the event-related potential (ERP) component features and different visual acuity
      levels by using the modified S1-S2 task under non-attention status. Three visual
      acuity levels were applied, each with four orientations of "E" optotype stimuli
      randomly presented in the center of the visual field while participants were
      required to concentrate on listening to stories. The results showed that the
      amplitudes of P1 and P3 as well as difference P3 were larger in supra-threshold
      condition. In threshold condition, larger amplitudes for both N2 and difference
      N2 exhibited in frontal and central areas. In sub-threshold condition, there was
      no endogenous component elicited by mismatch stimuli except smaller anterior N1.
      Meanwhile, the specific distributions of N1 and N2 were presented and compared
      with previous face processing. The findings showed that visual conflict
      processing took place not only at an early stage but also at the late period,
      which might be as the consequences of interaction between conflict strength and
      involuntary attention. We concluded that automatic conflict detecting of visual
      icons by the serial ERP components could distinguish different visual acuity
      levels. The involvement of endogenous components could reveal the specific
      mechanism of more precise and fine conflict identification of complex physical
      attributes under non-attention status, furthermore could be used as valid markers
      to estimate the magnitude of visual acuity objectively.

PMID- 29378282
TI  - Volumetric Associations Between Amygdala, Nucleus Accumbens, and Socially Anxious
      Tendencies in Healthy Women.
AB  - Socially anxious individuals report higher social fears and feelings of distress
      in interpersonal interactions. Structural neuroimaging studies indicate brain
      morphological abnormalities in patients with social anxiety disorder (SAD), but
      findings are heterogeneous and partially discrepant. Studies on structural
      correlates of socially anxious tendencies in participants without clinical
      diagnoses are scarce. Using structural magnetic resonance imaging, the present
      study examined the relationship between social interaction anxiety and gray
      matter (GM) volume in 38 healthy women. The amygdala and nucleus accumbens (NAcc)
      were defined as a priori regions of interest. Moreover, exploratory whole-brain
      analyses were conducted. Higher levels of social anxiety significantly predicted
      increased GM volume in the right amygdala [k = 262 voxels, voxel-level threshold
      at p < .05 (uncorrected), with a cluster-corrected significance level of p = 0.05
      calculated by Monte Carlo Simulations] and bilateral NAcc [left: k = 52 voxels,
      right: k = 49 voxels; at p < .05 (corrected for search volume)]. These
      relationships remained significant when controlling for a potential influence of
      trait anxiety. Additionally, socially anxious tendencies were associated with an
      enlarged striatum [i.e., putamen and caudate; left: k = 567 voxels, right: k =
      539 voxels; at p < .001 (uncorrected)]. Our findings indicate that higher social
      interaction anxiety in healthy individuals is related to amygdalar and striatal
      volumetric increases. These brain regions are known to be involved in social
      perception, anxiety, and the avoidance of harm. Future studies may clarify
      whether the observed morphological alterations constitute a structural
      vulnerability factor for SAD.

PMID- 29378283
TI  - Emotion lies in the eye of the listener: Emotional arousal to novel sounds is
      reflected in the sympathetic contribution to the pupil dilation response and the
      P3.
AB  - Novel sounds in the auditory oddball paradigm elicit a biphasic dilation of the
      pupil (PDR) and P3a as well as novelty P3 event-related potentials (ERPs). The
      biphasic PDR has been hypothesized to reflect the relaxation of the iris
      sphincter muscle due to parasympathetic inhibition and the constriction of the
      iris dilator muscle due to sympathetic activation. We measured the PDR and the P3
      to neutral and to emotionally arousing negative novels in dark and moderate
      lighting conditions. By means of principal component analysis (PCA) of the PDR
      data we extracted two components: the early one was absent in darkness and, thus,
      presumably reflects parasympathetic inhibition, whereas the late component
      occurred in darkness and light and presumably reflects sympathetic activation.
      Importantly, only this sympathetic late component was enhanced for emotionally
      arousing (as compared to neutral) sounds supporting the hypothesis that emotional
      arousal specifically activates the sympathetic nervous system. In the ERPs we
      observed P3a and novelty P3 in response to novel sounds. Both components were
      enhanced for emotionally arousing (as compared to neutral) novels. Our results
      demonstrate that sympathetic and parasympathetic contributions to the PDR can be
      separated and link emotional arousal to sympathetic nervous system activation.

PMID- 29378284
TI  - Measurement of attentional reserve and mental effort for cognitive workload
      assessment under various task demands during dual-task walking.
AB  - Previous work focused on cognitive workload assessment suggests EEG spectral
      content and component amplitudes of the event-related potential (ERP) waveform
      may index mental effort and attentional reserve, respectively. Although few
      studies have assessed attentional reserve and mental effort during upper
      extremity performance, none have employed a combined approach to measure
      cognitive workload during locomotion. Therefore, by systematically considering
      ERPs, spectral content and importantly their combination, this study aimed to
      examine whether concurrent changes in spectral content and ERPs could
      collectively serve as an index of cognitive workload during locomotion.
      Specifically, ERP and EEG biomarkers were assessed as participants performed a
      cognitive task under two levels of difficulty (easy or hard) and two conditions
      (seated or walking). Changes in attentional reserve and mental effort appeared to
      collectively index cognitive workload under varying demands due to changes in
      task difficulty or performance conditions. This work can inform cognitive
      workload assessment in patient populations with gait deficiencies for future
      applications.

PMID- 29378285
TI  - Knowledge of resting heart rate mediates the relationship between intelligence
      and the heartbeat counting task.
AB  - Evidence suggests that intelligence is positively associated with performance on
      the heartbeat counting task (HCT). The HCT is often employed as measure of
      interoception - the ability to perceive the internal state of one's body -
      however it's use remains controversial as performance on the HCT is strongly
      influenced by knowledge of resting heart rate. This raises the possibility that
      heart rate knowledge may mediate the previously-observed association between
      intelligence and HCT performance. Study One demonstrates an association between
      intelligence and HCT performance (N = 94), and Study Two demonstrates that this
      relationship is mediated by knowledge of the average resting heart rate (N =
      134). These data underscore the need to account for the influence of prior
      knowledge and beliefs when examining individual differences in cardiac
      interoceptive accuracy using the HCT.

PMID- 29378286
TI  - Impact of food allergy on the growth of children with moderate-severe atopic
      dermatitis.

PMID- 29378287
TI  - High number of early respiratory infections in association with allergic
      sensitization to mold promotes childhood asthma.

PMID- 29378288
TI  - Interleukins and their signaling pathways in the Reactome biological pathway
      database.
AB  - BACKGROUND: There is a wealth of biological pathway information available in the
      scientific literature, but it is spread across many thousands of publications.
      Alongside publications that contain definitive experimental discoveries are many
      others that have been dismissed as spurious, found to be irreproducible, or are
      contradicted by later results and consequently now considered controversial. Many
      descriptions and images of pathways are incomplete stylized representations that
      assume the reader is an expert and familiar with the established details of the
      process, which are consequently not fully explained. Pathway representations in
      publications frequently do not represent a complete, detailed, and unambiguous
      description of the molecules involved; their precise posttranslational state; or
      a full account of the molecular events they undergo while participating in a
      process. Although this might be sufficient to be interpreted by an expert reader,
      the lack of detail makes such pathways less useful and difficult to understand
      for anyone unfamiliar with the area and of limited use as the basis for
      computational models. OBJECTIVE: Reactome was established as a freely accessible
      knowledge base of human biological pathways. It is manually populated with
      interconnected molecular events that fully detail the molecular participants
      linked to published experimental data and background material by using a formal
      and open data structure that facilitates computational reuse. These data are
      accessible on a Web site in the form of pathway diagrams that have descriptive
      summaries and annotations and as downloadable data sets in several formats that
      can be reused with other computational tools. The entire database and all
      supporting software can be downloaded and reused under a Creative Commons
      license. METHODS: Pathways are authored by expert biologists who work with
      Reactome curators and editorial staff to represent the consensus in the field.
      Pathways are represented as interactive diagrams that include as much molecular
      detail as possible and are linked to literature citations that contain supporting
      experimental details. All newly created events undergo a peer-review process
      before they are added to the database and made available on the associated Web
      site. New content is added quarterly. RESULTS: The 63rd release of Reactome in
      December 2017 contains 10,996 human proteins participating in 11,426 events in
      2,179 pathways. In addition, analytic tools allow data set submission for the
      identification and visualization of pathway enrichment and representation of
      expression profiles as an overlay on Reactome pathways. Protein-protein and
      compound-protein interactions from several sources, including custom user data
      sets, can be added to extend pathways. Pathway diagrams and analytic result
      displays can be downloaded as editable images, human-readable reports, and files
      in several standard formats that are suitable for computational reuse. Reactome
      content is available programmatically through a REpresentational State Transfer
      (REST)-based content service and as a Neo4J graph database. Signaling pathways
      for IL-1 to IL-38 are hierarchically classified within the pathway "signaling by
      interleukins." The classification used is largely derived from Akdis et al.
      CONCLUSION: The addition to Reactome of a complete set of the known human
      interleukins, their receptors, and established signaling pathways linked to
      annotations of relevant aspects of immune function provides a significant
      computationally accessible resource of information about this important family.
      This information can be extended easily as new discoveries become accepted as the
      consensus in the field. A key aim for the future is to increase coverage of gene
      expression changes induced by interleukin signaling.

PMID- 29378289
TI  - PNMA family: Protein interaction network and cell signalling pathways implicated
      in cancer and apoptosis.
AB  - Paraneoplastic Ma Family (PNMA) comprises a growing number of family members
      which share relatively conserved protein sequences encoded by the human genome
      and is localized to several human chromosomes, including the X-chromosome. Based
      on sequence analysis, PNMA family members share sequence homology to the Gag
      protein of LTR retrotransposon, and several family members with aberrant protein
      expressions have been reported to be closely associated with the human
      Paraneoplastic Disorder (PND). In addition, gene mutations of specific members of
      PNMA family are known to be associated with human mental retardation or 3-M
      syndrome consisting of restrictive post-natal growth or dwarfism, and development
      of skeletal abnormalities. Other than sequence homology, the physiological
      function of many members in this family remains unclear. However, several members
      of this family have been characterized, including cell signalling events mediated
      by these proteins that are associated with apoptosis, and cancer in different
      cell types. Furthermore, while certain PNMA family members show restricted gene
      expression in the human brain and testis, other PNMA family members exhibit
      broader gene expression or preferential and selective protein interaction
      profiles, suggesting functional divergence within the family. Functional analysis
      of some members of this family have identified protein domains that are required
      for subcellular localization, protein-protein interactions, and cell signalling
      events which are the focus of this review paper.

PMID- 29378290
TI  - Antidepressant administration modulates stress-induced DNA methylation and DNA
      methyltransferase expression in rat prefrontal cortex and hippocampus.
AB  - Stress and antidepressant treatment can modulate DNA methylation in promoter
      region of genes related to neuroplasticity and mood regulation, thus implicating
      this epigenetic mechanism in depression neurobiology and treatment. Accordingly,
      systemic administration of DNA methyltransferase (DNMT) inhibitors induces
      antidepressant-like effects in rodents. DNA methylation is conveyed by DNMT 1, 3a
      and 3b isoforms, which are differentially expressed in the brain. In order to
      investigate if the behavioral effects of antidepressants could be associated with
      changes in DNA methylation and DNMT expression, we investigated the effects
      induced by acute and repeated antidepressant treatment on DNA methylation and
      DNMT expression (1, 3a and 3b isoforms) in different brain regions of rats
      exposed to a stress model of depression, the learned helplessness (LH).
      Therefore, rats were exposed to pretest and treated with one or seven injections
      of vehicle or imipramine (15 mg kg-1), with test session performed one hour after
      the last injection. Chronic, but not acute, imipramine administration attenuated
      escape failures during the test, a well described antidepressant-like effect in
      this model. DNA methylation and DNMT (1, 3a and 3b) levels were measured in the
      dorsal and ventral hippocampus (dHPC, vHPC) and in the prefrontal cortex (PFC) of
      rats exposed to stress and treatment. Stress increased DNA methylation, DNMT3a
      and DNMT3b expression in the dHPC and PFC. Chronic, but not acute, imipramine
      administration attenuated stress effects only in the PFC. These results suggest
      the regulation of DNA methylation in the PFC may be an important mechanism for
      antidepressant-like effects in the LH model.

PMID- 29378291
TI  - Glutamine/glutamate (Glx) concentration in prefrontal cortex predicts reversal
      learning performance in the marmoset.
AB  - This study used Magnetic Resonance Spectroscopy (MRS) to identify potential
      neurometabolitic markers of cognitive performance in male (n = 7) and female (n =
      8) middle-aged (~5 years old) common marmosets (Callithrix jacchus). Anesthetized
      marmosets were scanned with a 4.7 T/40 cm horizontal magnet equipped with 450
      mT/m magnetic field gradients and a 20 G/cm magnetic field gradient insert,
      within 3 months of completing the CANTAB serial Reversal Learning task.
      Neurometabolite concentrations of N-Acetyl Asparate, Myo-Inositol, Choline,
      Phosphocreatine + creatine, Glutamate and Glutamine were acquired from a 3 mm3
      voxel positioned in the Prefrontal Cortex (PFC). Males acquired the reversals
      (but not simple discriminations) faster than the females. Higher PFC Glx
      (glutamate + glutamine) concentration was associated with faster acquisition of
      the reversals. Interestingly, the correlation between cognitive performance and
      Glx was significant in males, but not in females. These results suggest that MRS
      is a useful tool to identify biochemical markers of cognitive performance in the
      healthy nonhuman primate brain and that biological sex modulates the relationship
      between neurochemical composition and cognition.

PMID- 29378292
TI  - Strategic neuronal encoding in medial prefrontal cortex of spatial working memory
      in the T-maze.
AB  - Strategic neuronal encoding in the medial prefrontal cortex (mPFC) of the rat was
      correlated with spatial working memory (sWM) assessed by behavior in the T-maze.
      Neurons increased their firing rate around choice, with the increase largely
      occurring before choice as a prospective encode of behavior. This could be
      classified as sensitive-to-spatial information or sensitive-to-choice outcome.
      The sensitivity-to-spatial choice was defined by distinct firing rate changes
      before left- or right-choice. The percentage of left-choice sensitive neurons was
      not different from the percentage of right-choice sensitive neurons. There was
      also location-related neuronal activity in which neurons fired at distinct rates
      when rats were in a left- or right-location. More neurons were sensitive to left
      location, as most of them were recorded from rats preferring to enter the right
      location. The sensitivity to outcome was defined by a distinct firing rate around
      correct or error choice. Significantly more neurons were sensitive to error
      outcome, and, among these, more preferred to encode prospectively, increasing
      firing in advance of an error outcome. Similar to single neuron activity, the
      mPFC enhanced its neuronal network as measured by the oscillation of local field
      potential. The maximum power of oscillation was around choice, and occurred
      slightly earlier before error versus before correct outcome. Thus, sWM modulation
      in the mPFC includes not only spatial, but also outcome-related inputs, and
      neuronal ensembles monitor behavioral outcome to make strategic adjustments
      ensuring successful task performance.

PMID- 29378293
TI  - NMDA receptors in the avian amygdala and the premotor arcopallium mediate
      distinct aspects of appetitive extinction learning.
AB  - Extinction learning is an essential mechanism that enables constant adaptation to
      ever-changing environmental conditions. The underlying neural circuit is mostly
      studied with rodent models using auditory cued fear conditioning. In order to
      uncover the variant and the invariant neural properties of extinction learning,
      we adopted pigeons as an animal model in an appetitive sign-tracking paradigm.
      The animals firstly learned to respond to two conditioned stimuli in two
      different contexts (CS-1 in context A and CS-2 in context B), before conditioned
      responses to the stimuli were extinguished in the opposite contexts (CS-1 in
      context B and CS-2 in context A). Subsequently, responding to both stimuli was
      tested in both contexts. Prior to extinction training, we locally injected the N
      methyl-d-aspartate receptor (NMDAR) antagonist 2-Amino-5-phosphonovaleric acid
      (APV) in either the amygdala or the (pre)motor arcopallium to investigate their
      involvement in extinction learning. Our findings suggest that the encoding of
      extinction memory required the activation of amygdala, as visible by an
      impairment of extinction acquisition by concurrent inactivation of local NMDARs.
      In contrast, consolidation and subsequent retrieval of extinction memory
      recruited the (pre)motor arcopallium. Also, the inactivation of arcopallial
      NMDARs induced a general motoric slowing during extinction training. Thus, our
      results reveal a double dissociation between arcopallium and amygdala with
      respect to acquisition and consolidation of extinction, respectively. Our study
      therefore provides new insights on the two key components of the avian extinction
      network and their resemblance to the data obtained from mammals, possibly
      indicating a shared neural mechanism underlying extinction learning shaped by
      evolution.

PMID- 29378294
TI  - Morphine antinociception on thermal sensitivity and place conditioning in male
      and female rats treated with intraplantar complete freund's adjuvant.
AB  - The experience of pain is characterized by the presence of a noxious sensory
      stimulus combined with negative affect, which is often treated clinically through
      administration of drugs such as morphine or other opioids. This study
      investigated the effects of morphine one and seven days after intraplantar
      administration of complete freund's adjuvant (CFA) in male and female rats.
      Hargreaves test for thermal nociception and conditioned place preference (CPP)
      were performed following subcutaneous administration of saline or morphine (1.0,
      4.0, 8.0, 12.0 mg/kg). Hargreaves test results revealed that male rats were more
      sensitive to morphine antinociceptive actions as compared to female rats one day
      after CFA treatment; however, this sex difference was not detected seven days
      after CFA treatment. One day after CFA treatment, morphine doses of 8.0 and 12.0
      mg/kg produced a CPP in male rats, while female rats exhibited CPP with only the
      12.0 mg/kg dose. Seven days after CFA treatment, both male and female rats
      exhibited a CPP with morphine doses of 4.0 mg/kg and higher. These results reveal
      sexually dimorphic properties of morphine in the paw withdrawal latencies and
      conditioned place preference models, representing reflexive and non-reflexive
      behavioral assays employed to examine inflammatory nociception. Our findings also
      suggest that antinociceptive effects of morphine are dynamic across early and
      later periods of CFA-induced inflammatory pain.

PMID- 29378295
TI  - A multidimensional approach to understanding the potential risk factors and
      covariates of adult picky eating.
AB  - OBJECTIVE: Adult picky eating (PE) has received increased attention in the eating
      behavior literature due to its important association with adult avoidant
      restrictive food intake disorder (ARFID). The current study tested a model of
      potential risk factors of adult PE behavior, including perceived early parental
      feeding practices. An exploratory model was also utilized to understand
      associations with different aspects of adult PE behaviors. METHODS: A sample of
      1339 US adults recruited through Amazon's MTurk completed an online survey that
      included the recently developed Adult Picky Eating Questionnaire (APEQ),
      retrospective reports of parental feeding practices, and other measures of eating
      behavior and demographic variables. A structural equation modeling procedure
      tested a series of regression models that included BMI and disordered eating
      behaviors as covariates. RESULTS: SEM modeling indicated that retrospective
      reports of greater parental pressure to eat, higher disgust sensitivity, lower PE
      age of onset, and experiencing an aversive food event were associated with
      general adult PE behavior. Results also indicated parental encouragement of
      healthy eating may be a protective factor, and that men endorsed higher levels of
      adult PE. Exploratory analyses indicated that cross-sectional predictors and
      covariates were differentially related to specific aspects of PE as measured by
      the APEQ subscales. CONCLUSIONS: Early experiences, including parental approaches
      to feeding, appear to be potential risk factors of PE behavior in adults. A
      nuanced understanding of adult PE is important for the prevention and treatment
      of severe PE behaviors, related psychosocial impairment, and ARFID.

PMID- 29378296
TI  - Metabolic signaling in the brain and the role of astrocytes in control of
      glutamate and GABA neurotransmission.
AB  - Neurotransmission mediated by the two amino acids glutamate and GABA is based on
      recycling of the two signaling molecules between the presynaptic nerve endings
      and the surrounding astrocytes. During the recycling process, a fraction of the
      transmitter pool is lost since both transmitters undergo oxidative metabolism.
      This loss must be replenished by de novo synthesis which involves the action of
      pyruvate carboxylase, aminotransferases, glutamate dehydrogenase and glutamine
      synthetase. Among these enzymes, pyruvate carboxylase and glutamine synthetase
      are selectively expressed in astrocytes and thus these cells are obligatory
      partners in synaptic replenishment of both glutamate and GABA. The cycling
      processes also involve transporters for glutamate, GABA and glutamine and the
      operation of these transporters is discussed. Additionally, astrocytes appear to
      be essential for production of the neuromodulators, citrate, glycine and d
      serine, aspects that will be briefly discussed.

PMID- 29378298
TI  - miR-34a deficiency in APP/PS1 mice promotes cognitive function by increasing
      synaptic plasticity via AMPA and NMDA receptors.
AB  - MicroRNA (miR)-34a was recently determined to contribute to the pathological
      development of Alzheimer's disease (AD). miR-34a deficiency significantly
      attenuates cognitive deficits in amyloid precursor protein (APP)/presenilin 1
      (PS1) mice; however, its role in early AD pathology and the underlying mechanisms
      remain elusive. Here, we confirmed that the increase of miR-34a expression in
      APP/PS1 mice was earlier than the relevant AD pathological characteristics, such
      as amyloid-beta production, amyloid plaque deposition, and cognitive deficits.
      Furthermore, because predicted miR-34a target genes were broadly linked to alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d
      aspartate (NMDA) receptors, we evaluated synaptic plasticity by investigating
      high-frequency conditioning tetanus-induced excitatory postsynaptic potential,
      which revealed that synaptic plasticity was promoted in miR-34a knockout/APP/PS1
      mice. Therefore, we assessed the expression of the presynaptic components
      synaptophysin and postsynaptic density protein 95 (PSD95) and found that
      synaptophysin and PSD95 were not altered by miR-34a deficiency. Additionally, the
      synaptic strength (vesicular fusion, vesicular docking, and transporting) was
      either not significantly changed. We also evaluated the levels of AMPA and NMDA
      receptors, which showed that the expression of AMPA and NMDA receptors was
      markedly upregulated in APP/PS1 mice with miR-34a deficiency. We conclude that
      miR-34a is involved in synaptic deficits in AD pathological development, which
      was, at least in part, due to the inhibition of NMDA (by miR-34a-5p) and AMPA (by
      miR-34a-3p) receptor expression.

PMID- 29378299
TI  - Advances in targeted therapies 2017.

PMID- 29378300
TI  - Assessment of brain oxygenation imbalance following soman exposure in rats.
AB  - Nerve agents (NAs) are potent organophosphorus (OP) compounds with applications
      in chemical warfare. OP compounds act by inhibiting acetylcholinesterase (AChE).
      Soman (O-pinacolyl methylphosphonofluoridate) is one of the most potent NAs. It
      is well known that small doses of NAs can be lethal, and that even non-lethal
      exposure leads to long-term mental debilitation/neurological damage. However, the
      neuropathology following exposure to sub-lethal nerve agents is not well
      understood. In this study, we examined changes in tissue oxygenation (pO2) in the
      cortex and hippocampus after a sub-lethal dose of soman [80-90 MUg/kg;
      subcutaneous]. pO2 changes can provide information regarding oxygen delivery and
      utilization and may be indicative of a disruption in cerebral blood flow and/or
      metabolism. Changes in oxygenation were measured with chronically implanted
      oxygen sensors in awake and freely moving rats. Measurements were taken before,
      during, and after soman-induced convulsive seizures. Soman exposure resulted in
      an immediate increase in pO2 in the cortex, followed by an even greater increase
      that precedes the onset of soman-induced convulsive seizures. The rise in
      hippocampus pO2 was delayed relative to the cortex, although the general pattern
      of brain oxygenation between these two regions was similar. After convulsive
      seizures began, pO2 levels declined but usually remained hyperoxygenated.
      Following the decline in pO2, low frequency cycles of large amplitude changes
      were observed in both the cortex and hippocampus. This pattern is consistent with
      recurring seizures. Measuring real-time changes in brain pO2 provides new
      information on the physiological status of the brain following soman exposure.
      These results highlight that the measurement of brain oxygenation could provide a
      sensitive marker of nerve agent exposure and serve as a biomarker for treatment
      studies.

PMID- 29378297
TI  - Deconstructing arousal into wakeful, autonomic and affective varieties.
AB  - Arousal plays a central role in a wide variety of phenomena, including
      wakefulness, autonomic function, affect and emotion. Despite its importance, it
      remains unclear as to how the neural mechanisms for arousal are organized across
      them. In this article, we review neuroscience findings for three of the most
      common origins of arousal: wakeful arousal, autonomic arousal, and affective
      arousal. Our review makes two overarching points. First, research conducted
      primarily in non-human animals underscores the importance of several subcortical
      nuclei that contribute to various sources of arousal, motivating the need for an
      integrative framework. Thus, we outline an integrative neural reference space as
      a key first step in developing a more systematic understanding of central nervous
      system contributions to arousal. Second, there is a translational gap between
      research on non-human animals, which emphasizes subcortical nuclei, and research
      on humans using non-invasive neuroimaging techniques, which focuses more on gross
      anatomical characterizations of cortical (e.g. network architectures including
      the default mode network) and subcortical structures. We forecast the importance
      of high-field neuroimaging in bridging this gap to examine how the various
      networks within the neural reference space for arousal operate across varieties
      of arousal-related phenomena.

PMID- 29378301
TI  - Connexin43 and zonula occludens-1 are targets of Akt in cardiomyocytes that
      correlate with cardiac contractile dysfunction in Akt deficient hearts.
AB  - While deletion of Akt1 results in a smaller heart size and Akt2-/- mice are
      mildly insulin resistant, Akt1-/-/Akt2-/- mice exhibit perinatal lethality,
      indicating a large degree of functional overlap between the isoforms of the
      serine/threonine kinase Akt. The present study aimed to determine the cooperative
      contribution of Akt1 and Akt2 on the structure and contractile function of adult
      hearts. To generate an inducible, cardiomyocyte-restricted Akt2 knockout (KO)
      model, Akt2flox/flox mice were crossed with tamoxifen-inducible MerCreMer
      transgenic (MCM) mice and germline Akt1-/- mice to generate the following
      genotypes:Akt1+/+; Akt2flox/flox (WT), Akt2flox/flox; alpha-MHC-MCM (iAkt2 KO),
      Akt1-/-, and Akt1-/-; Akt2flox/flox; alpha-MHC-MCM mice (Akt1-/-/iAkt2 KO). At 28
      days after the first tamoxifen injection, Akt1-/-/iAkt2 KO mice developed
      contractile dysfunction paralleling increased atrial and brain natriuretic
      peptide (ANP and BNP) levels, and repressed mitochondrial gene expression.
      Neither cardiac fibrosis nor apoptosis were detected in Akt1-/-/iAkt2 KO hearts.
      To explore potential molecular mechanisms for contractile dysfunction, we
      investigated myocardial microstructure before the onset of heart failure. At 3
      days after the first tamoxifen injection, Akt1-/-/iAkt2 KO hearts showed
      decreased expression of connexin43 (Cx43) and connexin-interacting protein zonula
      occludens-1 (ZO-1). Furthermore, Akt1/2 silencing significantly decreased both
      Cx43 and ZO-1 expression in cultured neonatal rat cardiomyocytes in concert with
      reduced beating frequency. Akt1 and Akt2 are required to maintain cardiac
      contraction. Loss of Akt signaling disrupts gap junction protein, which might
      precipitate early contractile dysfunction prior to heart failure in the absence
      of myocardial remodeling, such as hypertrophy, fibrosis, or cell death.

PMID- 29378302
TI  - Amyloid-beta oligomers synaptotoxicity: The emerging role of EphA4/c-Abl
      signaling in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by progressive memory loss and
      dementia. The strong correlation between cognitive decline and the loss of
      synapses supports the idea that synaptic damage is a relevant pathogenic
      mechanism underlying AD progression. It has been shown that amyloid beta
      oligomers (AbetaOs) induce synaptotoxicity ultimately leading to the reduction of
      dendritic spine density, which underlies cognitive damage. However, the signaling
      pathways connecting AbetaOs to synaptic dysfunction have not been completely
      elucidated. In this review, we have gathered evidence on AbetaOs receptors and
      the signaling pathways involved in synaptic damage. We make special emphasis on a
      new AbetaOs induced axis that involves the tyrosine kinase ephrin receptor A4
      (EphA4) and c-Abl tyrosine kinase activation. EphA4 is a key player in
      homeostatic plasticity, mediating dendritic spine remodeling and retraction.
      AbetaOs aberrantly activate EphA4 leading to dendritic spine elimination. c-Abl
      is activated in AbetaOs exposed neurons and in AD patient's brain, and the
      inhibition of activated c-Abl ameliorates cognitive deficits in AD mouse model.
      The EphA4 receptor activates c-Abl intracellular signaling. Therefore EphA4 is an
      emerging AbetaOs receptor and the activation of the EphA4/c-Abl axis would
      explain the synaptic spine alterations found in AD.

PMID- 29378303
TI  - Superior Survival of Black Versus White Patients Following Post-Transplant
      Cyclophosphamide-Based Haploidentical Transplantation for Adults with Hematologic
      Malignancy.
AB  - Available evidence from large registry studies has shown inferior survival for
      black adult patients following both unrelated donor and cord blood
      transplantation. Post-transplant cyclophosphamide (PTCy)-based haploidentical
      donor transplantation (HIDT) is being increasingly used in ethnic minorities.
      However, no studies of the impact of race on outcomes following HIDT have been
      reported. We analyzed 203 consecutive patients (123 white, 80 black) who
      underwent first HIDT using PTCy for hematologic malignancy at a single
      institution. Median recipient age was 53 (range, 19-75) years. Peripheral blood
      stem cells (PBSCs) were used as the stem cell source in 66% of patients, and
      conditioning intensity was myeloablative (MA) in 41%. After a median follow-up of
      36 months, the estimated 3-year overall survival (OS), disease-free survival
      (DFS), and cumulative incidence of relapse (CIR) were significantly better in
      black patients, compared with white patients (72% [95% confidence interval (CI),
      60% to 81%], 65% [95% CI, 52% to 75%], and 25% [95% CI, 16% to 35] versus 50%
      [95% CI, 40% to 59%], 45% [95% CI, 36% to 54%], and 39% [95% CI, 31% to 47%],
      respectively; P < .001 for OS and DFS, P = .015 for CIR). In contrast, 3-year
      nonrelapse mortality was similar between black (11%) and white (16%) patients, as
      were the incidences of acute graft-versus-host disease (GVHD) and moderate-to
      severe chronic GVHD. Improved survival was noted in all subgroups of black
      patients-younger versus older, male versus female, lower versus higher disease
      risk index, MA versus non-MA conditioning, or PBSC versus marrow stem cell
      source. In multivariate analysis, black race was independently associated with
      better OS (hazard ratio [HR], .47; P = .003), DFS (HR, .49; P = .003), and
      relapse (HR, .49; P = .01). Black patients achieve superior outcomes to their
      white counterparts following PTCy-based HIDT due to a decreased incidence of
      disease relapse.

PMID- 29378304
TI  - Low Rate of Cervical Cancer Screening among Women with Hematologic Malignancies
      after Stem Cell Transplant.
AB  - Annual cervical cancer screening with Papanicolaou (Pap) and human papillomavirus
      (HPV) testing after stem cell transplant (SCT) is recommended, but the uptake is
      unknown. We aimed to determine the prevalence and predictors of cervical cancer
      screening in patients with hematologic malignancies. We searched MarketScan
      Commercial Claims database for women who underwent allogeneic or autologous SCT.
      The primary outcome was cervical cancer screening, defined as procedures or
      abnormal results for HPV and/or Pap testing according administrative codes within
      2 years after SCT. A multivariable logistic regression model was fitted with
      cancer type, SCT year, age, geographic area, insurance plan, comorbidity, and
      presence of graft-versus-host disease (GVHD).The study included 1484 patients;
      1048 patients (70.6%) had autologous and 436 (29.4%) allogeneic SCT. Mean age was
      52.5 years. Overall, 660 patients (44.5%) had screening within 2 years after SCT,
      214 (49.1%) with allogeneic SCT and 446 (42.6%) with autologous SCT (P = .02). In
      the allogeneic SCT group, patients with GVHD had a lower rate of screening than
      patients without GVHD (42.5% versus 55.4%, P < .01), and GVHD was associated with
      lower odds of screening (odds ratio, .50; 95% confidence interval, .32 to .79).
      In the autologous SCT group, patients with comorbid medical conditions had a
      lower rate of screening than patients without comorbidity (36.0% versus 45.7%, P
      < .01). In both allogeneic and autologous SCT groups older patients had lower
      odds of screening. Cervical cancer screening rates after SCT are low,
      particularly in patients with GVHD, who are at significant risk of second
      malignancies. Future work is needed to develop strategies to increase uptake.

PMID- 29378305
TI  - Choice of time period to identify confounders for propensity score matching,
      affected the estimate: a retrospective cohort study of drug effectiveness in
      asthmatic children.
AB  - OBJECTIVES: To control for confounding by indication in comparative (drug)
      effectiveness studies, propensity score (PS) methods may be used. Since childhood
      diseases or outcomes often present as acute events, we compared the effect of
      using different look-back periods in electronic health-care data, to construct
      PSs. This was applied in our research on the effect of a combination of inhaled
      corticosteroids/long-acting beta-2 agonists (ICS + LABA), either as fixed
      combination or used as loose combination (2 separate inhaler devices) in the
      prevention of severe asthma exacerbations. METHODS: We created a cohort of
      children (5-17 years) diagnosed with asthma from the Dutch Integrated Primary
      Care information database. Within this cohort, we identified new users of ICS +
      LABA, either as fixed combination or loose combination (2 separate inhaler
      devices). The outcome of interest was severe asthma exacerbations. PSs for type
      of treatment were created using comorbidity and drug use history in different
      time windows: 1 week, 1 month, 3 months, 1 year, and full history prior to the
      start of treatment. PSs were used for matching subjects in both exposure groups.
      Time to first asthma exacerbation was analyzed with Cox proportional hazard
      regression. The results were compared with published clinical trials. RESULTS: Of
      39,682 asthmatic children, 3,500 (8.8%) were new users of either ICS + LABA fixed
      (3,324 [95.0%]) or loose (176 [5.0%]). The crude hazard ratio (HR) for a severe
      asthma exacerbation, comparing ICS + LABA fixed to loose was 0.37 (95% confidence
      interval [CI]: 0.20-0.66). PS-matched HRs (1 week, 1 month, 3 month, 1 year, and
      full history) were 0.48 (95% CI: 0.22-1.04); 0.60 (95% CI: 0.26-1.38), 0.69 (95%
      CI: 0.31-1.57), 0.56 (CI: 0.25-1.24), and 0.58 (CI: 0.24-1.36), respectively.
      CONCLUSIONS: PS matching can be used to control for confounding in pediatric
      comparative (drug) effectiveness studies, the impact of different look-back
      periods to implement the PS is important. Controlling for confounders occurring
      in the 3 months preceding drug exposure may yield results comparable to clinical
      trial results.

PMID- 29378306
TI  - Taenia Saginata in Third-Generation Capsule Endoscopy.

PMID- 29378308
TI  - Symptoms Do Not Correlate With Findings From Colonoscopy in Children With
      Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.
AB  - BACKGROUND & AIMS: Approximately 75% of children with primary sclerosing
      cholangitis (PSC) also have inflammatory bowel disease (IBD). IBD in patients
      with PSC (PSC-IBD) often has a unique phenotype, including a mild clinical
      course, yet it is associated with an increased risk of colorectal cancer compared
      with colonic IBD without PSC. We investigated whether subclinical endoscopic and
      histologic inflammation could account for the increased risk of colorectal cancer
      in patients with PSC-IBD, and whether these patients have increased fecal levels
      of calprotectin, a marker of inflammation. METHODS: We performed a prospective
      study of children (age, <18 y) with colonic IBD with and without PSC who
      underwent colonoscopy from February 1, 2016, through March 31, 2017, at the
      Hospital for Sick Children in Toronto, Canada. We collected pediatric ulcerative
      colitis activity index (PUCAI) scores (to measure symptoms) and fecal levels of
      calprotectin from 37 children with PSC-IBD and 50 children with only IBD
      (controls; UC or IBD-unclassified). Colonoscopies were scored using the Mayo
      endoscopic subscore and the UC Endoscopic Index of Severity (UCEIS) scores, and
      histologic activity was graded. Among patients in clinical remission, endoscopic
      scores and the odds of active endoscopic disease (based on a UCEIS score >=1)
      were compared between patients with and without PSC in univariate and
      multivariable analyses. Correlations between activity markers were compared
      between groups. The ability of fecal calprotectin to identify mucosal healing in
      patients with PSC-IBD was assessed using receiver operating characteristic curve
      analyses. Analogous analyses were performed for histologic activity. RESULTS:
      Patients with PSC-IBD in clinical remission had higher endoscopic scores and
      greater odds of active endoscopic disease than controls (odds ratio, 5.9; 95% CI,
      1.6-21.5). There was a higher degree of correlation between PUCAI and UCEIS
      scores in controls (r = 0.82) than in patients with PSC-IBD (r = 0.51; P = .01).
      Fecal levels of calprotectin correlated with UCEIS in patients with PSC-IBD (r =
      0.84) and controls (r = 0.82; P = .80). Fecal levels of calprotectin identified
      mucosal healing in patients with PSC-IBD with an area under the receiver
      operating characteristic curve of 0.94 (optimal cut-point, 93 MUg/g; 100%
      sensitivity and 92% specificity). Histologic activity scores and the odds of
      active histologic disease were also greater in patients in clinical remission
      with PSC-IBD than controls. CONCLUSIONS: Children with PSC-IBD in clinical
      remission, based on PUCAI scores, have a significantly higher risk of active
      endoscopic and histologic disease than children with colitis without PSC. Fecal
      levels of calprotectin correlate with endoscopic findings in pediatric patients
      with PSC-IBD; levels below 93 MUg/g are associated with mucosal healing.

PMID- 29378307
TI  - Among Patients With Nonalcoholic Fatty Liver Disease, Modest Alcohol Use Is
      Associated With Less Improvement in Histologic Steatosis and Steatohepatitis.
AB  - BACKGROUND & AIMS: Cross-sectional studies of patients with nonalcoholic fatty
      liver disease (NAFLD) have reported a lower prevalence of severe disease among
      modest drinkers compared with nondrinkers. We collected data from adult
      participants in the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network
      to evaluate the longitudinal association between modest use of alcohol and
      histology findings in patients with NAFLD, using paired liver biopsies collected
      more than 1 year apart. METHODS: We studied NASH Clinical Research Network
      participants 21 years or older, not receiving pharmacologic therapy, from whom 2
      or more liver biopsies and data on alcohol use within 2 years of the initial
      biopsy were available. Alcohol consumption was evaluated at study entry using the
      Alcohol Use Disorders Identification Test and Skinner Lifetime Drinking History
      questionnaires. At each follow-up visit participants were asked about alcohol use
      frequency, number of drinks on a typical day, and frequency of heavy drinking.
      The association between baseline drinking status and changes in fibrosis stage,
      NASH histology, and the NAFLD Activity Score and its individual components were
      evaluated by analysis of covariance. The association between change in drinking
      status and change in histology was evaluated using adjusted logistic regression.
      RESULTS: Of 285 participants (82% white, 70% female, mean age, 47 y) meeting
      entry criteria, 168 (59%) were modest alcohol users (<=2 drinks/d) and the
      remaining 117 were abstinent. At baseline, a higher proportion of modest alcohol
      users were white (86% vs 76% nonwhite) (P = .04) and a lower proportion of modest
      alcohol users were diagnosed with definite NASH (57% vs 74% without NASH; P =
      .01). During a mean follow-up period of 47 months between biopsies, nondrinkers
      had a greater mean reduction in steatosis grade (reduction, 0.49) than modest
      drinkers (reduction, 0.30; P = .04) and a greater reduction in mean level of
      aspartate transaminase (reduction, 7 U/L vs an increase of 2 U/L in modest
      drinkers; P = .04). Modest drinkers had significantly lower odds of NASH
      resolution compared with nondrinkers (adjusted odds ratio, 0.32; 95% CI, 0.11
      0.92; P = .04) on adjusted analysis. CONCLUSIONS: In a longitudinal analysis of
      liver biopsies from patients with NAFLD not receiving pharmacologic therapy,
      modest alcohol use was associated with less improvement in steatosis and level of
      aspartate transaminase, as well as lower odds of NASH resolution, compared with
      no use of alcohol.

PMID- 29378309
TI  - The Unregulated Probiotic Market.
AB  - BACKGROUND & AIMS: This narrative review provides an overview of the current
      regulation of probiotics, with a focus on those used for the dietary management
      of medical conditions (Medical Foods). FINDINGS: The probiotic market has grown
      rapidly, both for foods and supplements intended to enhance wellness in healthy
      individuals, and for preparations for the dietary management of disease.
      Regulation of probiotics varies between regions. Unless they make specific
      disease-related health claims, probiotics are regulated as food supplements and
      regulation is focused on the legitimacy of any claims, rather than efficacy,
      safety and quality. Many properties of probiotics are strain-specific, and safety
      and efficacy findings associated to specific formulations should not be
      generalized to other probiotic products. Manufacturing processes, conditions and
      ingredients are important determinants of product characteristics and changes to
      manufacturing are likely to give rise to a product not identical to the
      "original" in efficacy and safety if proper measures and controls are not taken.
      Current trademark law and the lack of stringent regulation of probiotic
      manufacturing mean that the trademark owner can commercialize any formulation
      under the same brand, even if significantly different from the original. These
      regulatory deficits may have serious consequences for patients where probiotics
      are used as part of clinical guideline-recommended management of serious
      conditions such as inflammatory bowel diseases, and may make doctors liable for
      prescribing a formulation not previously tested for safety and efficacy.
      CONCLUSIONS: Current regulation of probiotics is inadequate to protect consumers
      and doctors, especially when probiotics are aimed at the dietary management of
      serious conditions.

PMID- 29378310
TI  - Hepatitis C.

PMID- 29378311
TI  - High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing
      Cholangitis Associated With Inflammatory Bowel Disease.
AB  - BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) and primary
      sclerosing cholangitis (PSC, termed PSC-IBD) are at increased risk for colorectal
      cancer, but their risk following a diagnosis of low-grade dysplasia (LGD) is not
      well described. We aimed to determine the rate of advanced colorectal neoplasia
      (aCRN), defined as high-grade dysplasia and/or colorectal cancer, following a
      diagnosis of indefinite dysplasia or LGD in this population. METHODS: We
      performed a retrospective, longitudinal study of 1911 patients with colonic IBD
      (293 with PSC and 1618 without PSC) who underwent more than 2 surveillance
      colonoscopies from 2000 through 2015 in The Netherlands or the United States
      (9265 patient-years of follow-up evaluation). We collected data on clinical and
      demographic features of patients, as well as data from each surveillance
      colonoscopy and histologic report. For each surveillance colonoscopy, the
      severity of active inflammation was documented. The primary outcome was a
      diagnosis of aCRN during follow-up evaluation. We also investigated factors
      associated with aCRN in patients with or without a prior diagnosis of indefinite
      dysplasia or LGD. RESULTS: Patients with PSC-IBD had a 2-fold higher risk of
      developing aCRN than patients with non-PSC IBD. Mean inflammation scores did not
      differ significantly between patients with PSC-IBD (0.55) vs patients with non
      PSC IBD (0.56) (P = .89), nor did proportions of patients with LGD (21% of
      patients with PSC-IBD vs 18% of patients with non-PSC IBD) differ significantly
      (P = .37). However, the rate of aCRN following a diagnosis of LGD was
      significantly higher in patients with PSC-IBD (8.4 per 100 patient-years) than
      patients with non-PSC IBD (3.0 per 100 patient-years; P = .01). PSC (adjusted
      hazard ratio [aHR], 2.01; 95% CI, 1.09-3.71), increasing age (aHR 1.03; 95% CI,
      1.01-1.05), and active inflammation (aHR, 2.39; 95% CI, 1.63-3.49) were
      independent risk factors for aCRN. Dysplasia was more often endoscopically
      invisible in patients with PSC-IBD than in patients with non-PSC IBD.
      CONCLUSIONS: In a longitudinal study of almost 2000 patients with colonic IBD,
      PSC remained a strong independent risk factor for aCRN. Once LGD is detected,
      aCRN develops at a higher rate in patients with PSC and is more often
      endoscopically invisible than in patients with only IBD. Our findings support
      recommendations for careful annual colonoscopic surveillance for patients with
      IBD and PSC, and consideration of colectomy once LGD is detected.

PMID- 29378313
TI  - Rectal Bleeding Secondary to Viral and Fungal Colitidies in an Immunocompromised
      Host.

PMID- 29378314
TI  - Prevalence of Irritable Bowel Syndrome and Chronic Fatigue 10 Years After Giardia
      Infection.
AB  - BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a complication that can
      follow gastrointestinal infection, but it is not clear if patients also develop
      chronic fatigue. We investigated the prevalence and odds ratio of IBS and chronic
      fatigue 10 years after an outbreak of Giardia lamblia, compared with a control
      cohort, and changes in prevalence over time. METHODS: We performed a prospective
      follow-up study of 1252 laboratory-confirmed cases of giardiasis (exposed), which
      developed in Bergen, Norway in 2004. Statistics Norway provided us with
      information from 2504 unexposed individuals from Bergen, matched by age and sex
      (controls). Questionnaires were mailed to participants 3, 6, and 10 years after
      the outbreak. Results from the 3- and 6-year follow-up analyses have been
      published previously. We report the 10-year data and changes in prevalence among
      time points, determined by logistic regression using generalized estimating
      equations. RESULTS: The prevalence of IBS 10 years after the outbreak was 43% (n
      = 248) among 576 exposed individuals and 14% (n = 94) among 685 controls
      (adjusted odds ratio for development of IBS in exposed individuals, 4.74; 95% CI,
      3.61-6.23). At this time point, the prevalence of chronic fatigue was 26% (n =
      153) among 587 exposed individuals and 11% (n = 73) among 692 controls (adjusted
      odds ratio, 3.01; 95% CI, 2.22-4.08). The prevalence of IBS among exposed persons
      did not change significantly from 6 years after infection (40%) to 10 years after
      infection (43%; adjusted odds ratio for the change 1.03; 95% CI, 0.87-1.22).
      However, the prevalence of chronic fatigue decreased from 31% at 6 years after
      infection to 26% at 10 years after infection (adjusted odds ratio for the change
      0.74; 95% CI, 0.61-0.90). CONCLUSION: The prevalence of IBS did not change
      significantly from 6 years after an outbreak of Giardia lamblia infection in
      Norway to 10 years after. However, the prevalence of chronic fatigue decreased
      significantly from 6 to 10 years afterward. IBS and chronic fatigue were still
      associated with giardiasis 10 years after the outbreak.

PMID- 29378312
TI  - Under-dilated TIPS Associate With Efficacy and Reduced Encephalopathy in a
      Prospective, Non-randomized Study of Patients With Cirrhosis.
AB  - BACKGROUND & AIMS: Portosystemic encephalopathy (PSE) is a major complication of
      trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices
      are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that
      are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE
      SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain
      clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS
      self-expand to nominal diameter over time. METHODS: We performed a prospective,
      non-randomized study of 42 unselected patients with cirrhosis who received under
      dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more
      (controls) at referral centers in Italy. After completion of this study, dilation
      to 6 mm became the standard and 47 patients were included in a validation study.
      All patients were followed for 6 months; Doppler ultrasonography was performed 2
      weeks and 3 months after TIPS placement and every 6 months thereafter. Stability
      of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients
      with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary
      outcomes were incidence of at least 1 episode of PSE grade 2 or higher during
      follow up, incidence of recurrent variceal hemorrhage or ascites, incidence of
      shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval
      pressure gradient. RESULTS: PSE developed in a significantly lower proportion of
      patients with under-dilated TIPS (27%) than controls (54%) during the first year
      after the procedure (P = .015), but the proportions of patients with recurrent
      variceal hemorrhage or ascites did not differ significantly between groups. No
      TIPS occlusions were observed. These results were confirmed in the validation
      cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up
      period of 252 days after placement, none of the PTFE-SGs self-expanded to the
      nominal diameter in hemodynamically relevant sites (such as portal and hepatic
      vein vascular walls). CONCLUSIONS: In prospective, non-randomized study of
      patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS
      placement to be feasible, associated with lower rates of PSE, and effective.

PMID- 29378315
TI  - Systematic optimization of cell-free synthesized human endothelin B receptor
      folding.
AB  - Cell-free production of G-protein coupled receptors is becoming attractive for
      biochemical characterization, ligand screening or even structural purposes.
      However, despite high production levels within the range of mg/mL, the fraction
      of functionally folded receptor is frequently below 1%. In synthetic cell-free
      reactions, numerous factors that affect the efficient folding and stability of
      translated membrane proteins can be addressed by the appropriate design of the
      synthetic expression environment. We demonstrate the systematic quality
      optimization of the cell-free synthesized human endothelin B receptor by a
      combined approach of lipid screening, redox optimization, and molecular
      engineering. Key parameters for receptor folding are the implementation of
      nanodiscs, the selection of suitable lipid environments for co-translational
      solubilization, as well as providing an optimized redox system for essential
      disulfide bridge formation. In addition, enrichment with chaperones as well as
      receptor engineering by thermostabilization further supported the folding into
      ligand binding conformation. In summary, we provide evidence that the initial co
      translational folding process rather than long-term stability of the receptor is
      limiting. The folding efficiency could be improved by more than 103-fold and
      under optimized conditions, up to 1.6 nmol or ~100 ug of ligand binding competent
      receptor could be produced per mL of reaction mixture in a timescale of less than
      24 h. The identified parameters affect rather common characteristics of G-protein
      receptors and are thus likely to improve the folding of similar targets as well.
      The optimized process provides full-length receptors embedded in defined membrane
      environments and in quantities and quality sufficient for throughput screening
      applications.

PMID- 29378316
TI  - Fragment screening for drug leads by weak affinity chromatography (WAC-MS).
AB  - Fragment-based drug discovery is an important tool for design of small molecule
      hit-to-lead compounds against various biological targets. Several approved drugs
      have been derived from an initial fragment screen and many such candidates are in
      various stages of clinical trials. Finding fragment hits, that are suitable for
      optimisation by medicinal chemists, is still a challenge as the binding between
      the small fragment and its target is weak in the range of mM to uM of Kd and
      irrelevant non-specific interactions are abundant in this area of transient
      interactions. Fortunately, there are methods that can study weak interactions
      quite efficiently of which NMR, surface plasmon resonance (SPR) and X-ray
      crystallography are the most prominent. Now, a new technology based on zonal
      affinity chromatography, weak affinity chromatography (WAC), has been introduced
      which has remedied many of the problems with other technologies. By combining WAC
      with mass spectrometry (WAC-MS), it is a powerful tool to identify binders
      quantitatively in terms of affinity and kinetics either from fragment libraries
      or from complex mixtures of biological extracts. As WAC-MS can be multiplexed by
      analysing mixtures of fragments (20-100 fragments) in one sample, this approach
      yields high throughput, where a whole library of e.g. >2000 fragments can be
      analysed quantitatively within a day. WAC-MS is easy to perform, where the
      robustness and quality of HPLC is fully utilized. This review will highlight the
      rationale behind the application of WAC-MS for fragment screening in drug
      discovery.

PMID- 29378317
TI  - Decoding the auditory brain with canonical component analysis.
AB  - The relation between a stimulus and the evoked brain response can shed light on
      perceptual processes within the brain. Signals derived from this relation can
      also be harnessed to control external devices for Brain Computer Interface (BCI)
      applications. While the classic event-related potential (ERP) is appropriate for
      isolated stimuli, more sophisticated "decoding" strategies are needed to address
      continuous stimuli such as speech, music or environmental sounds. Here we
      describe an approach based on Canonical Correlation Analysis (CCA) that finds the
      optimal transform to apply to both the stimulus and the response to reveal
      correlations between the two. Compared to prior methods based on forward or
      backward models for stimulus-response mapping, CCA finds significantly higher
      correlation scores, thus providing increased sensitivity to relatively small
      effects, and supports classifier schemes that yield higher classification scores.
      CCA strips the brain response of variance unrelated to the stimulus, and the
      stimulus representation of variance that does not affect the response, and thus
      improves observations of the relation between stimulus and response.

PMID- 29378318
TI  - Hyperedge bundling: A practical solution to spurious interactions in MEG/EEG
      source connectivity analyses.
AB  - Inter-areal functional connectivity (FC), neuronal synchronization in particular,
      is thought to constitute a key systems-level mechanism for coordination of
      neuronal processing and communication between brain regions. Evidence to support
      this hypothesis has been gained largely using invasive electrophysiological
      approaches. In humans, neuronal activity can be non-invasively recorded only with
      magneto- and electroencephalography (MEG/EEG), which have been used to assess FC
      networks with high temporal resolution and whole-scalp coverage. However, even in
      source-reconstructed MEG/EEG data, signal mixing, or "source leakage", is a
      significant confounder for FC analyses and network localization. Signal mixing
      leads to two distinct kinds of false-positive observations: artificial
      interactions (AI) caused directly by mixing and spurious interactions (SI)
      arising indirectly from the spread of signals from true interacting sources to
      nearby false loci. To date, several interaction metrics have been developed to
      solve the AI problem, but the SI problem has remained largely intractable in
      MEG/EEG all-to-all source connectivity studies. Here, we advance a novel approach
      for correcting SIs in FC analyses using source-reconstructed MEG/EEG data. Our
      approach is to bundle observed FC connections into hyperedges by their adjacency
      in signal mixing. Using realistic simulations, we show here that bundling yields
      hyperedges with good separability of true positives and little loss in the true
      positive rate. Hyperedge bundling thus significantly decreases graph noise by
      minimizing the false-positive to true-positive ratio. Finally, we demonstrate the
      advantage of edge bundling in the visualization of large-scale cortical networks
      with real MEG data. We propose that hypergraphs yielded by bundling represent
      well the set of true cortical interactions that are detectable and dissociable in
      MEG/EEG connectivity analysis.

PMID- 29378319
TI  - Alter spontaneous activity in amygdala and vmPFC during fear consolidation
      following 24 h sleep deprivation.
AB  - Sleep deprivation (SD) has been associated with cognitive and emotional
      disruptions, however its impact on the acquisition of fear and subsequent fear
      memory consolidation remain unknown. To address this question, we measured human
      brain activity before and after fear acquisition under conditions of 24 h sleep
      deprivation versus normal sleep using resting-state functional magnetic resonance
      imaging (rs-fMRI). Additionally, we explored whether the fear acquisition-induced
      change of brain activity during the fear memory consolidation window can be
      predicted by subjective fear ratings and autonomic fear response, assessed by
      skin conductance responses (SCR) during acquisition. Behaviorally, the SD group
      demonstrated increased subjective and autonomic fear responses compared to
      controls at the stage of fear acquisition. During the stage of fear
      consolidation, the SD group displayed decreased ventromedial prefrontal cortex
      (vmPFC) activity and concomitantly increased amygdala activity. Moreover, in the
      SD group fear acquisition-induced brain activity changes in amygdala were
      positively correlated with both, subjective and autonomic fear indices during
      acquisition, whereas in controls changes vmPFC activity were positively
      correlated with fear indices during acquisition. Together, the present findings
      suggested that SD may weaken the top-down ability of the vmPFC to regulate
      amygdala activity during fear memory consolidation. Moreover, subjective and
      objective fear at fear acquisition stage can predict the change of brain activity
      in amygdala in fear memory consolidation following SD.

PMID- 29378320
TI  - White matter microstructural variability mediates the relation between obesity
      and cognition in healthy adults.
AB  - Obesity has been linked with structural and functional brain changes. However,
      the impact of obesity on brain and cognition in aging remains debatable,
      especially for white matter. We therefore aimed to determine the effects of
      obesity on white matter microstructure and potential implications for cognition
      in a well-characterized large cohort of healthy adults. In total, 1255
      participants (50% females, 19-80 years, BMI 16.8-50.2 kg/m2) with diffusion
      weighted magnetic resonance imaging at 3T were analysed. Tract-based spatial
      statistics (TBSS) probed whether body mass index (BMI) and waist-to-hip ratio
      (WHR) were related to fractional anisotropy (FA). We conducted partial
      correlations and mediation analyses to explore whether obesity or regional FA
      were related to cognitive performance. Analyses were adjusted for demographic,
      genetic, and obesity-associated confounders. Results showed that higher BMI and
      higher WHR were associated with lower FA in multiple white matter tracts (p <
      0.05, FWE-corrected). Mediation analyses provided evidence for indirect negative
      effects of higher BMI and higher WHR on executive functions and processing speed
      through lower FA in fiber tracts connecting (pre)frontal, visual, and associative
      areas (indirect paths, |beta| >= 0.01; 99% |CI| > 0). This large cross-sectional
      study showed that obesity is correlated with lower FA in multiple white matter
      tracts in otherwise healthy adults, independent of confounders. Moreover,
      although effect sizes were small, mediation results indicated that visceral
      obesity was linked to poorer executive functions and lower processing speed
      through lower FA in callosal and associative fiber tracts. Longitudinal studies
      are needed to support this hypothesis.

PMID- 29378321
TI  - Personalised genome editing - The future for corneal dystrophies.
AB  - The potential of personalised genome editing reaching the clinic has come to
      light due to advancements in the field of gene editing, namely the development of
      CRISPR/Cas9. The different mechanisms of repair used to resolve the double strand
      breaks (DSBs) mediated by Cas9 allow targeting of a wide range of disease causing
      mutations. Collectively, the corneal dystrophies offer an ideal platform for
      personalised genome editing; the majority of corneal dystrophies are monogenic,
      highly penetrant diseases with a known pattern of inheritance. This genetic
      background coupled with the accessibility, ease of visualisation and immune
      privilege status of the cornea make a gene editing strategy for the treatment of
      corneal dystrophies an attractive option. Off-target cleavage is a major concern
      for the therapeutic use of CRISPR/Cas9, thus current efforts in the gene editing
      field are focused on improving the genome-wide specificity of Cas9 to minimise
      the risk of off-target events. In addition, the delivery of CRISPR/Cas9 to
      different tissues is a key focus; various viral and non-viral platforms are being
      explored to develop a vehicle that is highly efficient, specific and non-toxic.
      The rapid pace and enthusiasm with which CRISPR/Cas9 has taken over biomedical
      research has ensured the personalised medicine revolution has been realised.
      CRISPR/Cas9 has recently been utilised in the first wave of clinical trials, and
      the potential for a genome editing therapy to treat corneal dystrophies looks
      promising. This review will discuss the current status of therapeutic gene
      editing in relation to the corneal dystrophies.

PMID- 29378322
TI  - Liver disturbances in activated phosphoinositide 3-kinase delta syndrome.

PMID- 29378323
TI  - Computational 3D imaging to quantify structural components and assembly of
      protein networks.
AB  - : Traditionally, protein structures have been described by the secondary
      structure architecture and fold arrangement. However, the relatively novel method
      of 3D confocal microscopy of fluorescent-protein-tagged networks in living cells
      allows resolving the detailed spatial organization of these networks. This
      provides new possibilities to predict network functionality, as structure and
      function seem to be linked at various scales. Here, we propose a quantitative
      approach using 3D confocal microscopy image data to describe protein networks
      based on their nano-structural characteristics. This analysis is constructed in
      four steps: (i) Segmentation of the microscopic raw data into a volume model and
      extraction of a spatial graph representing the protein network. (ii) Quantifying
      protein network gross morphology using the volume model. (iii) Quantifying
      protein network components using the spatial graph. (iv) Linking these two scales
      to obtain insights into network assembly. Here, we quantitatively describe the
      filamentous temperature sensitive Z protein network of the moss Physcomitrella
      patens and elucidate relations between network size and assembly details. Future
      applications will link network structure and functionality by tracking dynamic
      structural changes over time and comparing different states or types of networks,
      possibly allowing more precise identification of (mal) functions or the design of
      protein-engineered biomaterials for applications in regenerative medicine.
      STATEMENT OF SIGNIFICANCE: Protein networks are highly complex and dynamic
      structures that play various roles in biological environments. Analyzing the
      detailed spatial structure of these networks may lead to new insight into
      biological functions and malfunctions. Here, we propose a tool set that extracts
      structural information at two scales of the protein network and allows therefore
      to address questions such as "how is the network built?" or "how networks grow?".

PMID- 29378324
TI  - Adhesive free-standing multilayer films containing sulfated levan for biomedical
      applications.
AB  - : This work is the first reporting the use of layer-by-layer to produce adhesive
      free-standing (FS) films fully produced using natural-based macromolecules:
      chitosan (CHI), alginate (ALG) and sulfated levan (L-S). The deposition
      conditions of the natural polymers were studied through zeta potential
      measurements and quartz crystal microbalance with dissipation monitoring
      analysis. The properties of the FS films were evaluated and compared with the
      control ones composed of only CHI and ALG in order to assess the influence of
      levan polysaccharide introduced in the multilayers. Tensile tests, dynamic
      mechanical analysis and single lap shear strength tests were performed to
      evaluate the mechanical properties of the prepared FS films. The presence of L-S
      conferred both higher tensile strength and shear strength to the developed FS
      membranes. The results showed an adhesion strength 4 times higher than the
      control (CHI/ALG) FS films demonstrating the adhesive character of the FS films
      containing L-S. Morphological and topography studies were carried out revealing
      that the crosslinking reaction granted the L-S based FS film with a higher
      roughness and surface homogeneity. Preliminary biological assays were performed
      by cultivating myoblasts cells on the surface of the produced FS films. Both
      crosslinked and uncrosslinked FS films containing L-S were cytocompatible and
      myoconductive. STATEMENT OF SIGNIFICANCE: Sutures remain as the "gold standard"
      for wound closure and bleeding control; however they still have limitations such
      as, high infection rate, inconvenience in handling, and concern over possible
      transmission of blood-borne disease through the use of needles. One of the
      challenges of tissue engineering consist on the design and development of
      biocompatible tissue adhesives and sealants with high adhesion properties to
      repair or attach devices to tissues. In this work, the introduction of sulfated
      levan (L-S) on multilayered free-standing membranes was proposed to confer
      adhesive properties. Moreover, the films were myoconductive even in the absence
      of crosslinking just by the presence of L-S. This study provides a promising
      strategy to develop biological adhesives and for cardiac tissue engineering
      applications.

PMID- 29378325
TI  - Capacity of octacalcium phosphate to promote osteoblastic differentiation toward
      osteocytes in vitro.
AB  - : Octacalcium phosphate (OCP) has been shown to act as a nucleus for initial bone
      deposition and enhancing the early stages of osteoblastic differentiation.
      However, the effect on differentiation at the late stage into osteocytes has not
      been elucidated. The present study was designed to investigate whether OCP can
      promote the differentiation lineage from osteoblasts to late osteocytes using a
      clonal cell line IDG-SW3 compared to commercially available sintered beta
      tricalcium phosphate (beta-TCP) and hydroxyapatite (HA) in a transwell cell
      culture. Special attention was paid to detect the progress of OCP hydrolysis
      associated with ionic dissolution products from this material. OCP induced the
      appearance of an alkaline phosphatase (ALP) peak in the IDG-SW3 cells compared to
      beta-TCP and HA and increased SOST/sclerostin and FGF23 gene expression after 35
      days of incubation. Analyses by X-ray diffraction, curve fitting of Fourier
      transform infrared spectra, and acid phosphate inclusion of the materials showed
      that OCP tended to hydrolyze to an apatitic structure during the incubation.
      Since the hydrolysis enhanced inorganic phosphate ion (Pi) release from OCP in
      the media, IDG-SW3 cells were further incubated in the conditioned media with an
      increased concentration of Pi in the presence or absence of phosphonoformic acid
      (PFA), which is an inhibitor of Pi transport within the cells. An increase in Pi
      concentration up to 1.5 mM raised ALP activity, while its positive effect was
      eliminated in the presence of 0.1 to 0.5 mM PFA. Calcium ions did not show such
      an effect. These results indicate the stimulatory capacity of OCP on osteoblastic
      differentiation toward osteocytes. STATEMENT OF SIGNIFICANCE: Octacalcium
      phosphate (OCP) has been shown to have a superior osteoconductivity due to its
      capacity to enhance initial stage of osteoblast differentiation. However, the
      effect of OCP on the late osteoblastic differentiation into osteocyte is unknown.
      This study showed the capacity associated with the structural change of OCP. The
      data show that OCP released inorganic phosphate (Pi) ions while the hydrolysis
      advanced if soaked in the media, determined by chemical and physical analyses,
      and enhanced osteocytes differentiation of IDG-SW3 cells more than hydroxyapatite
      (HA) and beta-tricalcium phosphate (beta-TCP). Conditioned elevated Pi-containing
      media in the absence of OCP enhanced the osteocyte differentiation in the range
      of the concentration induced by OCP, the effect of which was cancelled by the
      inhibitor of Pi-transporters.

PMID- 29378326
TI  - Interplay between stiffness and degradation of architectured gelatin hydrogels
      leads to differential modulation of chondrogenesis in vitro and in vivo.
AB  - : The limited capacity of cartilage to heal large lesions through endogenous
      mechanisms has led to extensive effort to develop materials to facilitate
      chondrogenesis. Although physical-chemical properties of biomaterials have been
      shown to impact in vitro chondrogenesis, whether these findings are translatable
      in vivo is subject of debate. Herein, architectured 3D hydrogel scaffolds
      (ArcGel) (produced by crosslinking gelatin with ethyl lysine diisocyanate (LDI))
      were used as a model system to investigate the interplay between scaffold
      mechanical properties and degradation on matrix deposition by human articular
      chondrocytes (HAC) from healthy donors in vitro and in vivo. Using ArcGel
      scaffolds of different tensile and shear modulus, and degradation behavior; in
      this study, we compared the fate of ex vivo engineered ArcGels-chondrocytes
      constructs, i.e. the traditional tissue engineering approach, with thede
      novoformation of cartilaginous tissue in HAC laden ArcGels in an ectopic nude
      mouse model. While the softer and fast degrading ArcGel (LNCO3) was more
      efficient at promoting chondrogenic differentiation in vitro, upon ectopic
      implantation, the stiffer and slow degrading ArcGel (LNCO8) was superior in
      maintaining chondrogenic phenotype in HAC and retention of cartilaginous matrix.
      Furthermore, surprisingly the de novo formation of cartilage tissue was promoted
      only in LNCO8. Since HAC cultured for only three days in the LNCO8 environment
      showed upregulation of hypoxia-associated genes, this suggests a potential role
      for hypoxia in the observed in vivo outcomes. In summary, this study sheds light
      on how immediate environment (in vivo versus in vitro) can significantly impact
      the outcomes of cell-laden biomaterials. STATEMENT OF SIGNIFICANCE: In this
      study, 3D architectured hydrogels (ArcGels) with different mechanical and
      biodegradation properties were investigated for their potential to promote
      formation of cartilaginous matrix by human articular chondrocytes in vitro and in
      vivo. Two paradigms were explored (i) ex vivo engineering followed by in vivo
      implantation in ectopic site of nude mice and (ii) short in vitro culture (3
      days) followed by implantation to induce de novo cartilage formation. Softer and
      fast degrading ArcGel were better at promoting chondrogenesis in vitro, while
      stiffer and slow degrading ArcGel were strikingly superior in both maintaining
      chondrogenesis in vivo and inducing de novo formation of cartilage. Our findings
      highlight the importance of the interplay between scaffold mechanics and
      degradation in chondrogenesis.

PMID- 29378327
TI  - TRIB3 limits FGF21 induction during in vitro and in vivo nutrient deficiencies by
      inhibiting C/EBP-ATF response elements in the Fgf21 promoter.
AB  - Mammals must be able to endure periods of limited food availability, and the
      liver plays a central role in the adaptation to nutritional stresses. TRIB3
      (Tribbles homolog 3) is a cellular stress-inducible gene with a liver-centric
      expression pattern and it has been implicated in stress response regulation and
      metabolic control. In the current article, we study the involvement of TRIB3 in
      responses to nutrient deficiencies, including fasting for up to 48 h in mice. We
      show that hepatic expression of Trib3 is increased after 48 h of fasting and mice
      with a targeted deletion of the Trib3 gene present elevated hepatic triglyceride
      content and liver weight at 48 h, along with an upregulation of lipid utilization
      genes in the liver. Further, hepatic and serum levels of the metabolic stress
      hormone FGF21 are considerably increased in 48-h-fasted Trib3 knockout mice
      compared to wild type. Trib3 deficiency also leads to elevated FGF21 levels in
      the mouse liver during essential amino acid deficiency and in cultured mouse
      embryonic fibroblasts during glucose starvation. Reporter assays reveal that
      TRIB3 regulates FGF21 by inhibiting ATF4-mediated, C/EBP-ATF site-dependent
      activation of Fgf21 transcription. Based on chromatin immunoprecipitation from
      mouse liver, the binding of TRIB3 and ATF4, a transcription factor known to
      physically interact with TRIB3, is significantly increased at the Fgf21 promoter
      following 48 h of fasting. Thus, under nutrient-limiting conditions that
      stimulate ATF4 activity, TRIB3 is implicated in the regulation of metabolic
      adaptation by restraining the transcription of Fgf21.

PMID- 29378328
TI  - Transfer RNA modification and infection - Implications for pathogenicity and host
      responses.
AB  - Transfer RNA (tRNA) molecules are sumptuously decorated with evolutionary
      conserved post-transcriptional nucleoside modifications that are essential for
      structural stability and ensure efficient protein translation. The tRNA
      modification levels change significantly in response to physiological stresses,
      altering translation in a number of ways. For instance, tRNA hypomodification
      leads to translational slowdown, disrupting protein homeostasis and reducing
      cellular fitness. This highlights the importance of proper tRNA modification as a
      determinant for maintaining cellular function and viability during stress.
      Furthermore, the expression of several microbial virulence factors is induced by
      changes in environmental conditions; a process where tRNA 2-thiolation is
      unequivocal for pathogenicity. In this review, we discuss the multifaceted
      implications of tRNA modification for infection by examining the roles of
      nucleoside modification in tRNA biology. Future development of novel methods and
      combinatory utilization of existing technologies will bring tRNA modification
      mediated regulation of cellular immunity and pathogenicity to the limelight.

PMID- 29378329
TI  - miR-1275 controls granulosa cell apoptosis and estradiol synthesis by impairing
      LRH-1/CYP19A1 axis.
AB  - miR-1275 is one of the microRNAs (miRNAs) that are differentially expressed
      during follicular atresia in pig ovaries, as identified by a miRNA microarray
      assay in our previous study [1]. However, its functions in follicular atresia
      remain unknown. In this study, we showed that miR-1275 promotes early apoptosis
      of porcine granulosa cells (pGCs) and the initiation of follicular atresia, and
      inhibits E2 release and expression of CYP19A1, the key gene in E2 production.
      Bioinformatics and luciferase reporter assays revealed that liver receptor
      homolog (LRH)-1, not CYP19A1, is a direct functional target of miR-1275. In vitro
      overexpression and knockdown experiments showed that LRH-1 significantly
      repressed apoptosis and induced E2 secretion and CYP19A1 expression in pGCs. LRH
      1, whose expression was regulated by miR-1275, prevented apoptosis in pGCs.
      Furthermore, luciferase and chromatin immunoprecipitation assays demonstrated
      that LRH-1 protein bound to the CYP19A1 promoter and increased its activity. Our
      findings suggest that miR-1275 attenuates LRH-1 expression by directly binding to
      its 3'UTR. This prevents the interaction of LRH-1 protein with the CYP19A1
      promoter, represses E2 synthesis, promotes pGC apoptosis, and initiates
      follicular atresia in porcine ovaries.

PMID- 29378330
TI  - Dysregulation of cellular microRNAs by human oncogenic viruses - Implications for
      tumorigenesis.
AB  - Infection with certain animal and human viruses, often referred to as tumor
      viruses, induces oncogenic processes in their host. These viruses can induce
      tumorigenesis through direct and/or indirect mechanisms, and the regulation of
      microRNAs expression has been shown to play a key role in this process. Some
      human oncogenic viruses can express their own microRNAs; however, they all can
      dysregulate the expression of cellular microRNAs, facilitating their respective
      life cycles. The modulation of cellular microRNAs expression brings consequences
      to the host cells that may lead to malignant transformation, since microRNAs
      regulate the expression of genes involved in oncogenic pathways. This review
      focus on the mechanisms used by each human oncogenic virus to dysregulate the
      expression of cellular microRNAs, and their impact on tumorigenesis.

PMID- 29378331
TI  - Identification of the TXNIP IRES and characterization of the impact of regulatory
      IRES trans-acting factors.

PMID- 29378334
TI  - Roles of mammalian glutathione peroxidase and thioredoxin reductase enzymes in
      the cellular response to nitrosative stress.
AB  - Mammalian cells employ elaborate antioxidant systems to effectively handle
      reactive oxygen and nitrogen species (ROS and RNS). At the heart of these systems
      operate two selenoprotein families consisting of glutathione peroxidase (GPx) and
      thioredoxin reductase (TrxR) enzymes. Although mostly studied in the context of
      oxidative stress, considerable evidence has amassed to indicate that these
      selenoenzymes also play important roles in nitrosative stress responses. GPx and
      TrxR, together with their redox partners, metabolize nitrosothiols and
      peroxynitrite, two major RNS. As such, these enzymes play active roles in the
      cellular defense against nitrosative stress. However, under certain conditions,
      these enzymes are inactivated by nitrosothiols or peroxynitrite, which may
      exacerbate oxidative and nitrosative stress in cells. The selenol groups in the
      active sites of GPx and TrxR enzymes are critically involved in these beneficial
      and detrimental processes. Further elucidation of the biochemical interactions
      between distinct RNS and GPx/TrxR will lead to a better understanding of the
      roles of these selenoenzymes in cellular homeostasis and disease.

PMID- 29378333
TI  - Regulation of tRNA synthesis by the general transcription factors of RNA
      polymerase III - TFIIIB and TFIIIC, and by the MAF1 protein.
AB  - The synthesis of transfer RNA (tRNA) is directed by RNA polymerase III (Pol III)
      specialized in high-level transcription of short DNA templates. Pol III
      recruitment to tRNA genes is controlled by two general initiation factors, TFIIIB
      and TFIIIC. They are multi-protein complexes regulated at the level of expression
      of individual subunits, as well as through phosphorylation and interaction with
      partner proteins. Here, we describe particular aspects of TFIIIB and TFIIIC
      control in yeast and human cells. Under stress conditions, tRNA synthesis is
      negatively regulated by the MAF1 protein, which interacts directly with Pol III.
      Sequence and function of MAF1 are conserved among eukaryotic organisms from yeast
      to humans. MAF1 is a phosphoprotein which mediates diverse regulatory signals to
      Pol III. Interestingly, there is a subset of housekeeping tRNA genes, both in the
      yeast and human genome, which are less sensitive to MAF1-dependent repression.
      The possible mechanisms responsible for this differential regulation of tRNA
      synthesis by MAF1 are discussed.

PMID- 29378335
TI  - Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis.
AB  - Research into oxidative cell death is producing exciting new mechanisms, such as
      ferroptosis, in the neuropathologies of cerebral ischemia and hemorrhagic brain
      insults. Ferroptosis is an oxidative form of regulated necrotic cell death
      featuring glutathione (GSH) depletion, disrupted glutathione peroxidase-4 (GPX4)
      redox defense and detrimental lipid reactive oxygen species (ROS) formation.
      Further, our recent findings identified mitochondrial damage in models of
      oxidative glutamate toxicity, glutathione peroxidase depletion, and ferroptosis.
      Despite knowledge on the signaling pathways of ferroptosis increasing, the
      particular role of mitochondrial damage requires more in depth investigation in
      order to achieve effective treatment options targeting mitochondria. In the
      present study, we applied RSL3 to induce ferroptosis in neuronal HT22 cells and
      mouse embryonic fibroblasts. In both cell types, RSL3 mediated concentration
      dependent inhibition of GPX4, lipid peroxidation, enhanced mitochondrial
      fragmentation, loss of mitochondrial membrane potential, and reduced
      mitochondrial respiration. Ferroptosis inhibitors, such as deferoxamine,
      ferrostatin-1 and liproxstatin-1, but also CRISPR/Cas9 Bid knockout and the BID
      inhibitor BI-6c9 protected against RSL3 toxicity. We found compelling new
      information that the mitochondria-targeted ROS scavenger mitoquinone (MitoQ)
      preserved mitochondrial integrity and function, and cell viability despite
      significant loss of GPX4 expression and associated increases in general lipid
      peroxidation after exposure to RSL3. Our data demonstrate that rescuing
      mitochondrial integrity and function through the inhibition of BID or by the
      mitochondria-targeted ROS scavenger MitoQ serves as a most effective strategy in
      the prevention of ferroptosis in different cell types. These findings expose
      mitochondria as promising targets for novel therapeutic intervention strategies
      in oxidative cell death.

PMID- 29378336
TI  - Modulation of the rod outer segment aerobic metabolism diminishes the production
      of radicals due to light absorption.
AB  - Oxidative stress is a primary risk factor for both inflammatory and degenerative
      retinopathies. Our previous data on blue light-irradiated retinas demonstrated an
      oxidative stress higher in the rod outer segment (OS) than in the inner limb,
      leading to impairment of the rod OS extra-mitochondrial aerobic metabolism. Here
      the oxidative metabolism and Reactive Oxygen Intermediates (ROI) production was
      evaluated in purified bovine rod OS in function of exposure to different
      illumination conditions. A dose response was observed to varying light
      intensities and duration in terms of both ROI production and ATP synthesis.
      Pretreatment with resveratrol, inhibitor of F1Fo-ATP synthase, or metformin,
      inhibitor of the respiratory complex I, significantly diminished the ROI
      production. Metformin also diminished the rod OS Complex I activity and reduced
      the maximal OS response to light in ATP production. Data show for the first time
      the relationship existing in the rod OS between its -aerobic- metabolism, light
      absorption, and ROI production. A beneficial effect was exerted by metformin and
      resveratrol, in modulating the ROI production in the illuminated rod OS,
      suggestive of their beneficial action also in vivo. Data shed new light on
      preventative interventions for cone loss secondary to rod damage due to oxidative
      stress.

PMID- 29378337
TI  - Molecular response to nitrogen starvation by Frankia alni ACN14a revealed by
      transcriptomics and functional analysis with a fosmid library in Escherichia
      coli.
AB  - The transcriptome of Frankia alni strain ACN14a was compared between in vitro
      ammonium-replete (N-replete) and ammonium-free dinitrogen-fixing (N-fixing)
      conditions using DNA arrays. A Welch-test (p < 0.05) revealed significant
      upregulation of 252 genes under N-fixing vs. N-replete (fold-change (FC) >= 2),
      as well as significant downregulation of 48 other genes (FC <= 0.5).
      Interestingly, there were 104 Frankia genes upregulated in vitro that were also
      significantly upregulated in symbiosis with Alnus glutinosa, while the other 148
      genes were not, showing that the physiology of in vitro fixation is markedly
      different from that under symbiotic conditions. In particular,in vitro fixing
      cells were seen to upregulate genes identified as coding for a nitrite reductase,
      and amidases that were not upregulated in symbiosis. Confirmatory assays for
      nitrite reductase showed that Frankia indeed reduced nitrite and used it as a
      nitrogen source. An Escherichia coli fosmid clone carrying the nirB region was
      able to grow better in the presence of 5 mM nitrite than without it, confirming
      the function of the genome region. The physiological pattern that emerges shows
      that Frankia undergoes nitrogen starvation that induces a molecular response
      different from that seen in symbiosis.

PMID- 29378332
TI  - The histone demethylase Jmjd3 regulates zebrafish myeloid development by
      promoting spi1 expression.
AB  - The histone demethylase Jmjd3 plays a critical role in cell lineage specification
      and differentiation at various stages of development. However, its function
      during normal myeloid development remains poorly understood. Here, we carried out
      a systematic in vivo screen of epigenetic factors for their function in
      hematopoiesis and identified Jmjd3 as a new epigenetic factor that regulates
      myelopoiesis in zebrafish. We demonstrated that jmjd3 was essential for zebrafish
      primitive and definitive myelopoiesis, knockdown of jmjd3 suppressed the myeloid
      commitment and enhanced the erythroid commitment. Only overexpression of spi1 but
      not the other myeloid regulators rescued the myeloid development in jmjd3
      morphants. Furthermore, preliminary mechanistic studies demonstrated that Jmjd3
      could directly bind to the spi1 regulatory region to alleviate the repressive
      H3K27me3 modification and activate spi1 expression. Thus, our studies highlight
      that Jmjd3 is indispensable for early zebrafish myeloid development by promoting
      spi1 expression.

PMID- 29378338
TI  - Phenotypic and molecular characterization of Streptococcus agalactiae colonized
      in Chinese pregnant women: predominance of ST19/III and ST17/III.
AB  - Streptococcus agalactiae (GBS) remains a major cause of invasive infections in
      neonates and pregnant women. Our aim was to evaluate the phenotypic and molecular
      characteristics of GBS isolates in order to reveal potential relationships among
      molecular characteristics and differences in genotype-phenotype characteristics
      between ST17 and ST19. A total of 104 GBS isolates were collected from pregnant
      women. All isolates were tested for antibiotic susceptibility by disk diffusion
      method and molecular characteristics, including antibiotic-resistant genes,
      virulence genes, serotypes and STs. The prevalence of GBS colonization in
      pregnant women was 4.9%. All isolates were susceptible to penicillin, but a high
      prevalence of resistance was observed for tetracycline (76.9%) and erythromycin
      (72.1%), with the predominant resistant genes being tet(M), tet(O), erm(B) and
      mef (A/E). The most frequent serotypes were III, Ia and V, and the predominant
      STs were ST19, ST17, ST12, ST10 and ST651. A potential correlation existed
      between STs, serotypes and alp genes, with ST19/III/rib and ST17/III/rib as the
      most prevalent clones. Notably, we observed significant differences in phenotypic
      and genotypic characteristics between ST17 [levofloxacin-susceptible and tet(O)
      positive] and ST19 [levofloxacin-resistant and tet(O)-negative]. Our findings
      reveal a high prevalence of ST19/III and ST17/III and significant characteristic
      differences between them.

PMID- 29378339
TI  - The cfr and cfr-like multiple resistance genes.
AB  - The Cfr methyl transferase causes an RNA methylation of the bacterial ribosomes
      impeding reduced or abolished binding of many antibiotics acting at the peptidyl
      transferase center. It provides multi-resistance to eight classes of antibiotics,
      most of which are in clinical and veterinary use. The cfr gene is found in
      various bacteria in many geographical locations and placed on plasmids or
      associated with transposons. Cfr-related genes providing similar resistance have
      been identified in Bacillales, and now also in the pathogens Clostridium
      difficile and Enterococcus faecium. In addition, the presence of the cfr gene has
      been detected in harbours and food markets.

PMID- 29378340
TI  - Regulator DegU is required for multicellular behavior in Lysinibacillus
      sphaericus.
AB  - DegS and DegU make up a two component system belonging to a class of signal
      transduction systems that play important roles in a broad range of bacterial
      responses to the environment. However, little study has been done to explore the
      physiological functions of DegS-DegU in mosquitocidal Lysinibacillus sphaericus.
      In this study, it was found that deletion of degU or degS-degU inhibited the
      swarming motility, biofilm formation, sporulation and binary toxin production
      through regulating the related genes, and phosphorylation was necessary for the
      functions of DegU. Based on the findings, a regulation network mediated by DegU
      was delineated. Both DegU-pi and Spo0A-pi positively regulates genes which are
      linked with the transition from stage II to the end of the sporulation process
      and also influences the production of binary toxins via regulation on sigE. Both
      DegU-pi and Spo0A-pi negatively regulate abrB/sinR and influence the biofilm
      formation. DegU-pi can positively regulate the motility via the regulation on
      sigD. Whether the regulations are directly or indirectly need to be explored.
      Moreover, Spo0A-pi may indirectly regulate the swarming motility through
      negatively regulating DegU. It was concluded that DegU is a global
      transcriptional regulator on cell swarming motility, biofilm formation,
      sporulation and virulence in L. sphaericus.

PMID- 29378341
TI  - Nagarse treatment of cardiac subsarcolemmal and interfibrillar mitochondria leads
      to artefacts in mitochondrial protein quantification.
AB  - INTRODUCTION: In the heart, subsarcolemmal (SSM), interfibrillar (IFM) and
      perinuclear mitochondria represent three subtypes of mitochondria. The most
      commonly used protease during IFM isolation is the nagarse, however, its effect
      on the detection of mitochondrial proteins is still unclear. Therefore, we
      investigated whether nagarse treatment influences the quantification of
      mitochondrial proteins. METHODS: SSM and IFM were isolated from hearts of mice
      and rats. During IFM isolation, nagarse activity was either stopped by
      centrifugation (common protocol, IFM+N) or inhibited by phenylmethylsulfonyl
      fluoride (PMSF, IFM+N+I). The amounts of proteins located in different
      mitochondrial compartments (outer membrane: mitofusin 1 (MFN1) and 2 (MFN2);
      intermembrane space: p66shc; inner membrane (connexin 43 (Cx43)), and of protein
      deglycase DJ-1 were determined by Western blot. RESULTS: MFN2 and Cx43 were found
      predominantly in SSM isolated from mouse and rat hearts. MFN1 and p66shc were
      present in similar amounts in SSM and IFM+N, whereas the level of DJ-1 was higher
      in IFM+N compared to SSM. In IFM+N+I samples from mice, the amount of MFN2, but
      not that of Cx43 increased. Nagarse or nagarse inhibition by PMSF had no effect
      on oxygen consumption of SSM or IFM. DISCUSSION: Whereas the use of the common
      protocol indicates the localization of MFN2 predominantly in SSM, the inhibition
      of nagarse by PMSF increases the signal of MFN2 in IFM to that of in SSM,
      indicating an underestimation of MFN2 in IFM. Therefore, protease sensitivity
      should be considered when assessing distribution of mitochondrial proteins using
      nagarse-based isolation.

PMID- 29378342
TI  - Cefoxitin-based antibiotic therapy for extended-spectrum beta-lactamase-producing
      Enterobacteriaceae prostatitis: a prospective pilot study.
AB  - The emergence of extended-spectrum beta-lactamase-producing Enterobacteriaceae
      (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report
      the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A
      prospective study including patients with ESBL-E prostatitis resistant to
      trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March
      2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks
      in the case of acute bacterial prostatitis or 6 weeks in the case of chronic
      bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days.
      Urological investigations were performed to diagnose underlying urinary tract
      pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and
      6 months (M6) after the end of therapy. A total of 23 patients were included in
      the study. The median patient age was 74 years (range 48-88 years). Of the 23
      infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections.
      The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in
      10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23
      patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile
      in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary
      colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and
      5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was
      detected. Surgical treatment was required for 7/23 patients (30%). In conclusion,
      cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E
      infections such as prostatitis.

PMID- 29378343
TI  - Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration Manifesting as Acute
      Cerebellitis with Posterior Cranial Fossa Hypertension.
AB  - BACKGROUND: Paraneoplastic cerebellar degeneration (PCD) is a rare complication
      of some malignant cancers. It is most commonly described in women with
      gynecologic or breast malignancies; however, there have been reports in other
      types of cancers. Symptoms include ataxia, dysarthria, and tremors, which could
      be the first manifestations of an underlying malignancy. CASE DESCRIPTION: A 50
      year-old woman had an acute PCD with anti-Yo antibodies from an underlying breast
      invasive ductal carcinoma. She presented with intracranial hypertension in the
      posterior cranial fossa that required an emergent decompressive craniectomy.
      CONCLUSIONS: PCD is an uncommon disease that may manifest initially as posterior
      cranial fossa hypertension and subsequent acute hydrocephalus owing to diffuse
      cerebellar swelling. To our knowledge, this is the first described case of an
      anti-Yo PCD that has manifested as acute posterior cranial fossa hypertension
      owing to diffuse cerebellar edema. Early diagnosis and treatment should be
      pursued to improve long-term outcomes.

PMID- 29378344
TI  - Minimally Invasive Approaches for Anterior Skull Base Meningiomas: Supraorbital
      Eyebrow, Endoscopic Endonasal, or a Combination of Both? Anatomic Study,
      Limitations, and Surgical Application.
AB  - BACKGROUND: Minimally invasive accesses to the anterior skull base include the
      endoscopic endonasal approach (EEA) and the supraorbital eyebrow approach. These
      2 are often seen as competing approaches, not alternative or combinatory
      approaches. In this study, we evaluated the anatomic limitations of each approach
      and the combined approach for accessing the anterior skull base. METHODS: Ten
      neurovascular injected cadaver heads were used for the study. The supraorbital
      approach to the anterior skull base was performed on 5 heads, and EEA was done on
      the other 5 heads. Then, the supraorbital approach was added to the 5 heads
      receiving EEA. Visualization and surgical limitations were recorded by the
      ability to perform resection of the crista galli, anterior clinoid, cribriform
      plate, and planum sellae. RESULTS: The maximal lateral extension of EEA for
      anterior skull base was the midorbit line anteriorly but narrowing down toward
      the orbital apex. The limitation of the supraorbital approach was found mostly
      medial and anterior. Drilling of anterior skull base was impossible medially
      between the sphenoethmoidal suture and the posterior aspect of the crista galli.
      The combined approach showed complementary areas of visualization and surgical
      maneuverability. Three clinical cases were presented to illustrate the
      indications for the stand-alone supraorbital approach, EEA, and combined
      approach. CONCLUSION: The limitations of the EEA when dealing with lateral
      extension of anterior skull base meningiomas, and the limitations of the
      supraorbital eyebrow approach for medial skull base drilling and reconstruction,
      can be overcome by a judicious, anatomically based combination of both
      approaches.

PMID- 29378346
TI  - Making Sense: Robotic Skin That Senses Proprioception, Temperature, and Pressure.

PMID- 29378345
TI  - Ectopic Prolactinoma Presenting as Bacterial Meningitis: A Diagnostic Conundrum.
AB  - BACKGROUND: Prolactinomas may rarely present with meningitis and cerebrospinal
      fluid (CSF) rhinorrhea secondary to erosion of the wall of the sella turcica. It
      is even more uncommon for this abnormal communication to be caused by an ectopic
      prolactinoma arising from the sphenoid sinus and eroding into the sella. This
      atypical growth pattern makes diagnosis very difficult because there may be no
      displacement of the normal pituitary gland. The first reported case of a patient
      with an ectopic prolactinoma originating within the sphenoid sinus presenting
      primarily with meningitis is presented, and the management strategy and surgical
      and nonsurgical treatment options are discussed. CASE DESCRIPTION: A 48-year-old
      woman presented with confusion, low-pressure headache, and fever. A lumbar
      puncture revealed Streptococcus pneumoniae meningitis, and she was placed on
      intravenous penicillin G. After initiation of antibiotics, she noticed salty
      tasting postnasal fluid leakage. Imaging was remarkable for bony erosion of the
      sphenoid sinus wall by a soft tissue mass growing from within the sinus, with no
      disruption of the normal pituitary gland. A biopsy was then performed with an
      endoscopic transnasal transsphenoidal approach, and the CSF leak was repaired
      with a pedicled nasoseptal flap. The final pathology was prolactinoma, and she
      was placed on cabergoline. CONCLUSIONS: Ectopic prolactinomas may rarely present
      as meningitis secondary to retrograde transmission of bacteria through a bony
      defect in the sphenoid sinus, and must be included in the differential diagnosis
      of any sphenoid sinus mass. Management should first address the infection,
      followed by surgical repair of the bony defect.

PMID- 29378347
TI  - Extraventricular Neurocytoma in the Left Frontal Lobe: A Case Report and
      Literature Review.
AB  - BACKGROUND: Neurocytoma is a rare brain neoplasm of neuroepithelial origin that
      occurs predominantly in the ventricular system adjacent to the interventricular
      foramen and septum pellucidum. However, extraventricular neurocytoma is an
      extremely rare entity, with poor clinical, radiologic, and histopathological
      characterization. Here we report a case of an extraventricular parafalcine
      neurocytoma in the left frontal lobe. We also examine previously reported cases
      of extraventricular neurocytoma in an attempt to provide an up-to-date summary of
      the condition. METHODS: A literature search was performed using PubMed with
      specific key terms, inclusion criteria, and exclusion criteria. Selected case
      studies and case series were then compared, and statistical analyses were
      performed where appropriate. We report a 59-year-old woman presenting with
      weakness in her right leg and urinary incontinence. Physical examination revealed
      muscle strength of grade 3/5 in the right lower extremity. Brain magnetic
      resonance imaging showed a parafalcine mass in the left frontal lobe, with
      perilesional edema; the cerebral falx and lateral ventricle were shifted due to
      the compression. Gross total resection was performed. RESULTS: Histopathological
      examination revealed a neurocytoma. Immunohistochemical staining showed diffuse
      positivity for synaptophysin. MIB-1 staining for Ki-67 antibody showed a labeling
      index of 20%. No adjuvant radiation or chemotherapy was administered. Brain
      computed tomography performed at a 3-month follow-up showed no signs of
      recurrence. CONCLUSION: Extraventricular neurocytoma occurring in the brain
      parenchyma is a very rare central nervous system tumor. Its clinical and
      radiologic manifestations are nonspecific. The diagnosis depends on
      histopathological and immunohistochemical examination. Surgical resection should
      be the first-choice treatment.

PMID- 29378348
TI  - Sexual Dysfunction in Unmedicated Patients with Schizophrenia and in Healthy
      Controls.
AB  - INTRODUCTION: Sexual dysfunction figures prominently in patients with
      schizophrenia; however, medication effects may play a role. The objective of this
      case control study was to assess differences in the presence of sexual
      dysfunction in unmedicated patients with schizophrenia versus healthy controls.
      METHODS: Sexual dysfunction was assessed using the Derogatis Inventory for Sexual
      Function self-rating in a cross-sectional design controlling for age and gender
      effects. A brief sexual anamnesis was applied to describe the psychosocial
      background of the mostly male sample further. RESULTS: Results show a significant
      difference with patients reporting more problems in most domains and with a
      significant correlation between severity of psychosis (Positive and Negative
      Syndrome Scale total scores) and the impairment of orgasm experience. The study
      revealed reduced sexual activities and less pleasure during sexual activities of
      patients. DISCUSSION: This study implies that schizophrenia has an impact on the
      presence of sexual dysfunction and that sexual dysfunction is partly independent
      of antipsychotic treatment. Since the sample consisted mostly of first-episode
      males, conclusions might only be valid for this subgroup.

PMID- 29378349
TI  - [Intrathecal Nursinersen Therapy in Children with Spinal Muscular Atrophy and
      Spinal Deformities].

PMID- 29378350
TI  - [Unexpected consequences of standard ENT therapy].

PMID- 29378351
TI  - [Optimized Transition from Inpatient Stroke Rehabilitation to Home Care - Current
      Practice and Analysis of Factors Influencing Transition].
AB  - OBJECTIVE: To identify factors influencing the current transition practice and to
      generate aspects to improve transition. METHODS: Expert interviews and group
      discussions with health care professionals; a scoping review and a standardized
      interview with stroke patients 6 weeks after discharge via telephone. RESULTS: 14
      expert interviews and 3 group discussions (n=18) were conducted. Factors
      influencing transition at home were communication of professionals between and
      within settings, social support and role behavior of stroke patients. The
      interviews (n=110) revealed realization of recommendations towards consultations
      of medical specialists of 37%, and of outpatient therapies up to 86%. The scoping
      review included 7 systematic reviews, 21 randomised trials and 5 controlled
      trials to patient education, information and counselling, Early Supported
      Discharge models, stroke liaison services, team conferences and integrated care
      pathways. CONCLUSION: A structured approach is needed which has to consider the
      complexity of the transition process.

PMID- 29378353
TI  - Contact System Activation and Cancer: New Insights in the Pathophysiology of
      Cancer-Associated Thrombosis.
AB  - Cancer induces a systemic hypercoagulable state that elevates the baseline
      thrombotic risk of affected patients. This hypercoagulable state reflects a
      complex interplay between cancer cells and host cells and the coagulation system
      as part of the host response to cancer. Although the tissue factor (TF)/factor
      VIIa pathway is proposed to be the principal initiator of fibrin formation in
      cancer patients, clinical studies have not shown a consistent relationship
      between circulating TF levels (often measured as plasma microvesicle-associated
      TF) and the risk of thrombosis. A renewed interest in the role of the contact
      pathway in thrombosis has evolved over the past decade, raising the question of
      its role in the pathogenesis of thrombotic complications in cancer. Recent
      observations have documented the presence of activation of the contact system in
      gastrointestinal, lung, breast and prostate cancers. Although the assays used to
      measure contact activation differ, and despite the absence of standardization of
      methodologies, it is clear that both the intrinsic and extrinsic pathways may be
      activated in cancer. This review will focus on recent findings concerning the
      role of activation of the contact system in cancer-associated hypercoagulability
      and thrombosis. An improved understanding of the pathophysiology of these
      mechanisms may lead to personalized antithrombotic protocols with improved
      efficacy and safety compared with currently available therapies.

PMID- 29378354
TI  - Urban Particulate Matter Induces Changes in Gene Expression in Vascular
      Endothelial Cells that Are Associated with Altered Clot Structure In Vitro.
AB  - BACKGROUND:  Particulate matter contained in ambient air pollution has been
      associated with cardiovascular diseases in several epidemiological studies.
      OBJECTIVE:  The aim of this study was to investigate the potential for urban
      particulate matter to induce changes in clot structure through interaction with
      vascular endothelial cells. METHODS:  We examined the structure of clots formed
      on human umbilical vascular endothelial cells that had been treated with various
      types of particles versus those formed on untreated cells. Particles used were
      standard reference particulate matter from diesel engine emissions (SRM2975) and
      urban ambient collection (SRM2787). RESULTS:  There was a dose-dependent increase
      in fibre density in clots formed on particle-treated endothelial cells. It was
      also found that exposure to the particles induced increased expression of tissue
      factor and reduced expression of thrombomodulin genes as measured by real-time
      polymerase chain reaction and increased expression of von Willebrand factor and
      plasminogen activation inhibitor-1 as measured by ELISA. CONCLUSION:  These
      changes are consistent with increased procoagulant activity of air pollution
      particulate matter-treated endothelial cells and suggest that particulate matter
      has the potential to promote clot formation through changes induced in
      endothelial genes controlling clot formation.

PMID- 29378356
TI  - A Mechanistic Model to Quantify von Willebrand Factor Release, Survival and
      Proteolysis in Patients with von Willebrand Disease.
AB  - A reduced von Willebrand factor (VWF) synthesis or survival, or its increased
      proteolysis, alone or in combination, contributes to the development of von
      Willebrand disease (VWD).We describe a new, simple mechanistic model for
      exploring how VWF behaves in well-defined forms of VWD after its 1-desamino-8-D
      arginine vasopressin (DDAVP)-induced release from endothelial cells. We aimed to
      ascertain whether the model can consistently predict VWF kinetic changes. The
      study involved 9 patients with VWD types Vicenza (a paradigmatic form with a
      reduced VWF survival), 8 type 2B, 2 type 2A-I, 1 type 2A-II (associated with an
      increased VWF proteolysis), and 42 normal controls, whose VWF levels were
      measured after a 24-hour-long DDAVP test. The rate constants considered were: k0,
      associated with the VWF release phase; k1, illustrating the phase of conversion
      from high- to low-molecular-weight VWF multimers; and ke, associated with the VWF
      elimination phase. The amount of VWF released (D) was also measured. ke and D
      were significantly higher in O than in non-O blood group controls; k1 was also
      higher, but less markedly so. All the parameters were accelerated in type
      Vicenza, especially ke (p < 0.0001), which explains the significant reduction in
      VWF half-life. In types 2B and 2A-II, k1 was one order of magnitude higher than
      in controls, which explains their loss of large VWF multimers. All parameters
      except ke were lower in type 2A-I.The proposed mechanistic model clearly
      describes the altered biochemical pathways in well-characterized VWD, prompting
      us to suggest that it might help clarify elusive forms of VWD too.

PMID- 29378355
TI  - A Genome-wide Study of Common and Rare Genetic Variants Associated with
      Circulating Thrombin Activatable Fibrinolysis Inhibitor.
AB  - Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a central role in
      haemostasis, and plasma TAFI concentrations are heritable. Candidate gene studies
      have identified several variants within the gene encoding TAFI, CPB2, that
      explain part of the estimated heritability. Here, we describe an exploratory
      genome-wide association study to identify novel variants within and outside of
      the CPB2 locus that influence plasma concentrations of intact TAFI and/or the
      extent of TAFI activation (measured by released TAFI activation peptide, TAFI-AP)
      amongst 3,260 subjects from Southern Sweden. We also explored the role of rare
      variants on the HumanExome BeadChip. We confirmed the association with previously
      reported common variants in CPB2 for both intact TAFI and TAFI-AP, and discovered
      novel associations with variants in putative CPB2 enhancers. We identified a gene
      based association with intact TAFI at CPB2 (PSKAT-O = 2.8 * 10-8), driven by two
      novel rare nonsynonymous single nucleotide polymorphisms (SNPs; I420N and D177G).
      Carriers of the rare variant of D177G (rs140446990; MAF 0.2%) had lower intact
      TAFI and TAFI-AP concentrations compared with non-carriers (intact TAFI,
      geometric mean 53 vs. 78%, PT-test = 5 * 10-7; TAFI-AP 63 vs. 99%, PT-test = 7.2
      * 10-4). For TAFI-AP, we identified a genome-wide significant association at an
      intergenic region of chromosome 3p14.1 and five gene-based associations (all
      PSKAT-O < 5 * 10-6). Using well-characterized assays together with a genome-wide
      association study and a rare-variant approach, we verified CPB2 to be the primary
      determinant of TAFI concentrations and identified putative secondary loci
      (candidate variants and genes) associated with intact TAFI and TAFI-AP that
      require independent validation.

PMID- 29378357
TI  - Predictors of Post-Thrombotic Ulcer after Acute DVT: The RIETE Registry.
AB  - In patients with deep-vein thrombosis (DVT) in the lower limbs, venous ulcer is
      the most debilitating and end-stage clinical expression of the post-thrombotic
      syndrome (PTS). To date, risk factors for PTS-related ulcer in DVT patients have
      not been identified.We used the international observational RIETE registry to
      assess the evolution of PTS signs and symptoms during a 3-year follow-up period
      and to identify independent predictors of PTS ulcer at 1 year in patients with
      acute DVT.Among 1,866 eligible patients, cumulative rates of PTS ulcer at 1, 2
      and 3 years were 2.7% (n = 50), 4.3% (n = 54) and 7.1% (n = 60), respectively.
      The proportion of patients with PTS symptoms at 1, 2 or 3 years remained stable
      (~40%), while the proportion of patients with PTS signs increased slightly over
      time (from 49 to 53%). Prior history of venous thromboembolism (VTE) (odds ratio
      [OR] = 5.5 [2.8-10.9]), diabetes (OR = 2.3 [1.1-4.7]), pre-existing leg
      varicosities (OR = 3.2 [1.7-6.1]) and male sex (OR = 2.5 [1.3-5.1]) independently
      increased the risk of PTS ulcer at 1 year. Obesity also increased the risk but
      failed to reach statistical significance (OR = 1.8 [0.9-3.3]). DVT treatment
      characteristics (duration or drug) did not influence the risk.Our results
      evidence that after acute DVT, pre-existing leg varicosities, prior venous
      thromboembolism, diabetes and male gender independently increased the risk for
      PTS ulcer. This suggests that clinicians should consider strategies aimed to
      prevent ulcers in high-risk DVT patients, such as preventing VTE recurrence, use
      of stockings in those with pre-existing venous insufficiency, careful monitoring
      of diabetic patients and encouraging weight loss in obese patients.

PMID- 29378358
TI  - Chemical Footprinting Reveals Conformational Changes Following Activation of
      Factor XI.
AB  - Coagulation factor XI is activated by thrombin or factor XIIa resulting in a
      conformational change that converts the catalytic domain into its active form and
      exposing exosites for factor IX on the apple domains. Although crystal structures
      of the zymogen factor XI and the catalytic domain of the protease are available,
      the structure of the apple domains and hence the interactions with the catalytic
      domain in factor XIa are unknown. We now used chemical footprinting to identify
      lysine residue containing regions that undergo a conformational change following
      activation of factor XI. To this end, we employed tandem mass tag in conjunction
      with mass spectrometry. Fifty-two unique peptides were identified, covering 37 of
      the 41 lysine residues present in factor XI. Two identified lysine residues that
      showed altered flexibility upon activation were mutated to study their
      contribution in factor XI stability or enzymatic activity. Lys357, part of the
      connecting loop between A4 and the catalytic domain, was more reactive in factor
      XIa but mutation of this lysine residue did not impact on factor XIa activity.
      Lys516 and its possible interactor Glu380 are located in the catalytic domain and
      are covered by the activation loop of factor XIa. Mutating Glu380 enhanced Arg369
      cleavage and thrombin generation in plasma. In conclusion, we have identified
      novel regions that undergo a conformational change following activation. This
      information improves knowledge about factor XI and will contribute to development
      of novel inhibitors or activators for this coagulation protein.

PMID- 29378359
TI  - Dimeric Glycoprotein VI Binds to Collagen but Not to Fibrin.
AB  - Platelet glycoprotein VI (GPVI) acts as a decisive collagen receptor in
      atherothrombosis. Besides collagen, injured atherosclerotic plaques expose tissue
      factor (TF) that triggers fibrin formation. Two recent studies reported that
      platelet GPVI also functions as fibrin receptor, which would importantly widen
      the mode of action of GPVI-targeted antithrombotic drugs. We studied the binding
      of two GPVI fusion proteins to fibrin under static and arterial flow conditions.
      Fibrin was prepared from purified fibrinogen or generated more physiologically
      from endogenous fibrinogen by coagulating plasma with thrombin. Fibrin formation
      was also triggered by exposing TF-coated surfaces or human atherosclerotic plaque
      slices to arterially flowing blood. By binding studies and advanced optical
      imaging, we found that recombinant dimeric GPVI-Fc fusion proteins with Fc from
      either IgG1 (GPVI-Fc1) or IgG2 (GPVI-Fc2) bound to collagen fibres, but neither
      to fibrin prepared from purified fibrinogen obtained from three suppliers, nor to
      physiological fibrin formed by thrombin in plasma or triggered by exposing TF or
      atherosclerotic plaque slices to arterially flowing blood. Our findings do not
      support a role of dimeric platelet GPVI as receptor for fibrin. This is important
      for the understanding of plaque-triggered platelet thrombus formation and is
      clinically relevant for future GPVI-targeting therapies with recombinant GPVI-Fc
      and anti-GPVI antibodies.

PMID- 29378360
TI  - Activated Factor X-Based versus Thrombin-Based Antithrombin Testing in
      Thrombophilia Workup in the DOAC Era.
AB  - Antithrombin (AT) activity tests are used for diagnosing hereditary AT
      deficiency, a main genetic determinant of thrombophilia. They are either based on
      inhibition of thrombin (FIIa) or activated factor X (FXa). FXa-based assays have
      been suggested to be preferable to FIIa-based assays due to their higher
      sensitivity for certain AT deficiency causing mutations. To assess the
      performance of these two methods in a real-world scenario, 745 consecutively
      collected samples from patients referred to our institute during a 3-month period
      for thrombophilia testing were analysed. In samples from patients not receiving
      direct-acting oral anticoagulants or heparins (n = 485), both methods showed good
      agreement (r = 0.874, Bland-Altman limits of agreement 6.57%, -15.76%). While
      similar results were obtained in patients receiving low-molecular-weight heparin
      (LMWH, n = 76, r = 0.891, 4.09%, -14.35%), the agreement was lower in patients
      receiving rivaroxaban (n = 86, r = 0.570, 5.97%, -49.43%) and apixaban (n = 72, r
      = 0.735, 3.77%, -42.45%). Direct FXa inhibitors but not LMWH increased FXa-based
      assay results in a dose-dependent manner, while the FIIa-based test was
      unaffected. Both assay types were equally successful in detecting hereditary AT
      deficiency in our study population, as samples from 9 out of 10 patients with AT
      deficiency causing mutations were detected by each method. These data suggest
      that FXa-based AT testing can be preferred over FIIa-based methods only in the
      absence of direct FXa inhibitors. In patients receiving direct FXa inhibitors, AT
      activity testing should be performed using FIIa-based assays.

PMID- 29378352
TI  - Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht
      Consensus Conference on Thrombosis.
AB  - Atherothrombosis is a leading cause of cardiovascular mortality and long-term
      morbidity. Platelets and coagulation proteases, interacting with circulating
      cells and in different vascular beds, modify several complex pathologies
      including atherosclerosis. In the second Maastricht Consensus Conference on
      Thrombosis, this theme was addressed by diverse scientists from bench to bedside.
      All presentations were discussed with audience members and the results of these
      discussions were incorporated in the final document that presents a state-of-the
      art reflection of expert opinions and consensus recommendations regarding the
      following five topics: 1. Risk factors, biomarkers and plaque instability: In
      atherothrombosis research, more focus on the contribution of specific risk
      factors like ectopic fat needs to be considered; definitions of atherothrombosis
      are important distinguishing different phases of disease, including plaque
      (in)stability; proteomic and metabolomics data are to be added to genetic
      information. 2. Circulating cells including platelets and atherothrombosis:
      Mechanisms of leukocyte and macrophage plasticity, migration, and transformation
      in murine atherosclerosis need to be considered; disease mechanism-based
      biomarkers need to be identified; experimental systems are needed that
      incorporate whole-blood flow to understand how red blood cells influence thrombus
      formation and stability; knowledge on platelet heterogeneity and priming
      conditions needs to be translated toward the in vivo situation. 3. Coagulation
      proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in
      thrombosis including the lower margins of this factor related to safe and
      effective antithrombotic therapy needs to be established; FXI is a key regulator
      in linking platelets, thrombin generation, and inflammatory mechanisms in a renin
      angiotensin dependent manner; however, the impact on thrombin-dependent PAR
      signaling needs further study; the fundamental mechanisms in FXIII biology and
      biochemistry and its impact on thrombus biophysical characteristics need to be
      explored; the interactions of red cells and fibrin formation and its consequences
      for thrombus formation and lysis need to be addressed. Platelet-fibrin
      interactions are pivotal determinants of clot formation and stability with
      potential therapeutic consequences. 4. Preventive and acute treatment of
      atherothrombosis and arterial embolism; novel ways and tailoring? The role of
      protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic
      therapy merits study; ongoing trials on platelet function test-based antiplatelet
      therapy adjustment support development of practically feasible tests; risk scores
      for patients with atrial fibrillation need refinement, taking new biomarkers
      including coagulation into account; risk scores that consider organ system
      differences in bleeding may have added value; all forms of oral anticoagulant
      treatment require better organization, including education and emergency access;
      laboratory testing still needs rapidly available sensitive tests with short
      turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and
      ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis
      are needed; further studies on novel modified activated protein C-based agents
      are required including its cytoprotective properties; new avenues for optimizing
      treatment of patients with ischaemic stroke are needed, also including novel
      agents that modify fibrinolytic activity (aimed at plasminogen activator
      inhibitor-1 and thrombin activatable fibrinolysis inhibitor.

PMID- 29378361
TI  - Assessment of Thrombotic Risk in Atrial Fibrillation with Ultrasound Molecular
      Imaging of P-Selectin.
AB  - Molecular imaging of inflammatory mediators in atria may contribute to thrombotic
      risk assessment of atrial fibrillation (AF). We investigated the feasibility of
      ultrasound molecular imaging (UMI) targeted to P-selectin to assess thrombotic
      risk in AF. Rat AF models were established with rapid atrial pacing. Microbubbles
      targeted to P-selectin were injected into the rats, followed by left atrial (LA)
      UMI examination. Furthermore, P-selectin, platelets (PLTs), fibrin and tissue
      factor (TF) of LA were detected by histopathology and scanning electron
      microscopy. Plasma levels of P-selectin, thrombin-antithrombin complex (TAT) and
      prothrombin fragment 1 + 2 (F1 + 2) were measured by enzyme-linked immunosorbent
      assay. The data showed that P-selectin in LA was correlated with PLT, fibrin and
      TF (r = 0.735, p < 0.05; r = 0.827, p < 0.05; r = 0.785, p < 0.05, respectively).
      The plasma level of P-selectin was correlated with the expression of TAT and F1 +
      2 (r = 0.866, p < 0.05; r = 0.916, p < 0.05, respectively). The contrast video
      intensity of adhered microbubbles targeted to P-selectin was correlated with the
      levels of P-selectin, PLT and fibrin in LA (r = 0.768, p < 0.05; r = 0.798, p <
      0.05; r = 0.745, p < 0.05, respectively). In conclusion, P-selectin may serve as
      a biomarker for thrombotic risk in AF and can be quantified by UMI to assess
      thrombotic risk.

PMID- 29378362
TI  - Inhibitory Effects of an Orally Active Thromboxane A2 Receptor Antagonist,
      nstpbp5185, on Atherosclerosis in ApoE-Deficient Mice.
AB  - Thromboxane A2 (TXA2) activation of TP receptor has been shown contributing to
      the progression and acute complications of atherosclerosis including endothelial
      dysfunction, platelet hyperactivity and inflammation. Growing evidence suggests
      that TP receptor may represent as a therapeutic target in atherosclerosis and
      related cardiovascular diseases. We investigated whether nstpbp5185, an orally
      active TP receptor antagonist, exhibits protective effects against
      atherosclerotic progression. Nstpbp5185 and aspirin were orally administered
      daily for 12 weeks in high-cholesterol-fed ApoE-deficient mice to examine their
      anti-atherosclerosis effects. Total cholesterol, low-density lipoprotein
      cholesterol and triglycerides were slightly decreased in nstpbp5185-treated mice.
      However, nstpbp5185 significantly reduced neointima formation and aortic
      atherosclerotic lesion area. Nstpbp5185 increased serum paraoxonase 1 activity.
      In contrast, plasma levels of interleukin-6 and tumour necrosis factor-alpha were
      reduced in nstpbp5185-treated mice. Plasma level of TXA2 metabolite, TXB2, was
      lower in both aspirin- and nstpbp5185-treated mice, while the urinary 2,3-dinor-6
      keto PGF1alpha (a PGI2 metabolite) and plasma iPF2alpha-III were not altered.
      Moreover, nstpbp5185 neither caused gastric ulceration nor affected the
      haemostatic response. Nstpbp5185 also inhibited U46619-induced endothelial NF-kB
      activation, ICAM-1 and VCAM-1 expression, as well as monocyte adhesion to
      endothelial cells. In conclusion, nstpbp5185 may represent as an ideal, safe and
      efficacious agent for preventing atherosclerotic progression through its
      antiplatelet, anti-inflammatory and antioxidative activities.

PMID- 29378363
TI  - Severe Wound Healing Impairment in a Patient with Dysfibrinogenaemia.

PMID- 29378364
TI  - External Validation of the WILL-BLEED Risk Score.

PMID- 29378365
TI  - Video Comment on Emo E. van Halsema et al.

PMID- 29378366
TI  - Video Comment on Irina Gessl et al.

PMID- 29378367
TI  - Video Comment on Yu Bai et al.

PMID- 29378368
TI  - Video Comment on Stefan K. Golder et al.

PMID- 29378369
TI  - Video Comment on Yasushi Yamasaki et al.

PMID- 29378370
TI  - Why don't endoscopists follow guideline recommendations and how can we improve
      adherence?

PMID- 29378371
TI  - Treatment of Zenker's diverticulum: different tastes all leading to the same
      flavor?

PMID- 29378372
TI  - Double incision and snare resection in symptomatic Zenker's diverticulum: a
      modification of the stag-beetle knife technique.

PMID- 29378373
TI  - Differences in endoscopic techniques for symptomatic Zenker's diverticulum.

PMID- 29378374
TI  - [French comment on article Stent placement for benign esophageal leaks,
      perforations, and fistulae: a clinical prediction rule for successful leakage
      control].

PMID- 29378375
TI  - [French comment on article Surveillance colonoscopy in Austria: Are we following
      the guidelines?]

PMID- 29378376
TI  - [French comment on article Impact of preprocedure simethicone on adenoma
      detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized
      controlled trial].

PMID- 29378377
TI  - Anti-Mullerian Hormone and Inhibin B Levels in Obese Boys; Relations with
      Cardiovascular Risk Factors.
AB  - OBJECTIVE: Obesity may reduce sertoli cell functions in men. The aim of the study
      was to investigate antimullerian hormone (AMH) and inhibin B levels (sertoli cell
      markers) in obese boys and their relations to cardiovascular risk factors such as
      insulin sensitivity index, aortic intima media thickness (aIMT) and high
      sensitive c-reactive protein (hsCRP). PATIENTS, METHODS: 121 obese and 38 healthy
      lean adolescents were included in the study. Serum AMH, inhibin B, gonadotropins,
      total testosterone, lipids, hsCRP, glucose and insulin levels were detected and
      analyzed. Insulin resistance was analyzed using the homeostasis model assessment
      (HOMA-IR). aIMT was measured by high-resolution B-mode ultrasonography. RESULTS:
      Serum AMH, inhibin B and total testosterone levels were lower in the obese
      adolescents (p=0.01, p=0.009 and p=0.002, respectively). aIMT measurements
      (p<0.001, 0.63+/-0.09 and 0.47+/-0.06 mm, respectively) and hsCRP levels
      (p<0.001, 2.5+/-0.4 and 0.66+/-0.69 mg/L, respectively) were significantly
      increased in the obese group. Obese with IR group had decreased AMH levels
      (p=0.02, 53.0+/-20.5 and 66.7+/-19.5 ng/mL, respectively) and increased
      triglycerides, HOMA-IR, aIMT measurements than non-IR obese group. AMH levels
      were correlated negatively with body mass index (r:-0.108, p=0.03), HOMA-IR (r:
      0.358, p=0.003) and fasting insulin levels (r:-0.389, p=0.001) in obese group
      with IR. CONCLUSION: We found that concentrations of both sertoli cell markers
      (AMH and inhibin B) were significantly lower in obese pubertal boys especially in
      obese with IR. Obesity and IR might be important factors for the sertoli cell
      impairment in pubertal boys.

PMID- 29378378
TI  - The Variation of Disulfides in the Progression of Type 2 Diabetes Mellitus.
AB  - AIM: The purpose of this study was to examine thiol-disulfide balance in patients
      with type 2 diabetes mellitus. METHODS: This study included 32 subjects with
      known type 2 diabetes mellitus without complications, 30 patients with type 2
      diabetes mellitus with complications, 28 newly diagnosed patients with type 2
      diabetes mellitus, and 45 healthy individuals. Thiol-disulfide profile tests were
      quantified in all groups. RESULTS: Compared to the control group, patients in
      each of the diabetic groups had significantly lower native and total thiol
      levels, higher disulfide levels, and higher disulfide/native thiol and
      disulfide/total thiol ratios (p<0.05 for all). Disulfide levels were
      significantly lower in the newly diagnosed group than in other diabetic groups
      (p<0.05). There were significant associations between glycemic parameters and
      thiol-disulfide tests (p<0.05). CONCLUSIONS: A disequilibrium between thiol
      disulfide pairs occurs in patients with type 2 diabetes mellitus, and a gradual
      increase to disulfide levels may contribute to the disease's severity.
      Deteriorated thiol-disulfide homeostasis may be relevant to the pathophysiology
      of type 2 diabetes mellitus.

PMID- 29378379
TI  - [Biofabrication: new approaches for tissue regeneration].
AB  - BACKGROUND: The advent of Tissue Engineering (TE) in the early 1990ies was
      fostered by the increasing need for functional tissue and organ replacement.
      Classical TE was based on the combination of carrier matrices, cells and growth
      factors to reconstitute lost or damaged tissue and organs. Despite considerable
      results in vitro and in experimental settings the lack of early vascularization
      has hampered its translation into daily clinical practice so far. A new field of
      research, called "biofabrication" utilizing latest 3D printing technologies aims
      at hierarchically and spatially incorporating different cells, biomaterials and
      molecules into a matrix to alleviate a directed maturation of artificial tissue.
      MATERIALS AND METHODS: A literature research of the relevant publications
      regarding biofabrication and bioprinting was performed using the PubMed data
      base. Relevant papers were selected and evaluated with secondary analysis of
      specific citations on the bioprinting techniques. RESULTS: 180 relevant papers
      containing the key words were identified and evaluated. Basic principles into the
      developing field of bioprinting technology could be discerned. Key elements
      comprise the high-throughput assembly of cells and the fabrication of complex and
      functional hierarchically organized tissue constructs. Five relevant
      technological principles for bioprinting were identified, such as
      stereolithography, extrusion-based printing, laser-assisted printing, inkjet
      based printing and nano-bioprinting. The different technical methods of 3D
      printing were found to be associated with various positive but also negative
      effects on cells and proteins during the printing process. Research efforts in
      this field obviously aim towards the development of optimizing the so called
      bioinks and the printing technologies. CONCLUSION: This review details the
      evolution of the classical methods of TE in Regenerative Medicine into the
      evolving field of biofabrication by bioprinting. The advantages of 3D bioprinting
      over traditional tissue engineering techniques are based on the assembling of
      cells, biomaterials and biomolecules in a spatially controlled manner to
      reproduce native tissue macro-, micro- and nanoarchitectures, that can be
      utilized not only to potentially produce functional replacement tissues or organs
      but also to serve as new models for basic research. Mimicking the stromal
      microenvironment of tumor cells to study the process of tumor formation and
      progression, metastasis, angiogenesis and modulation of the associated processes
      is one of these applications under research. To this end a close collaboration of
      specialists from the fields of engineering, biomaterial science, cell biology and
      reconstructive microsurgery will be necessary to develop future strategies that
      can overcome current limitations of tissue generation.

PMID- 29378380
TI  - Intra-Arterial Thrombolytic Therapy Is Not a Therapeutic Option for Filler
      Related Central Retinal Artery Occlusion.
AB  - Cosmetic facial filler-related central retinal artery occlusion (CRAO) is a
      devastating complication of facial hyaluronic acid (HA) injection and can be
      managed by intra-arterial thrombolytic therapy (IATT). The authors report on a 20
      year-old woman who developed unilateral CRAO due to facial HA injection and who,
      despite prompt IATT, lost vision. A review of the related literature found 14
      other female patients who developed cosmetic facial filler-related CRAO and
      accepted IATT management. In no case was vision loss clinically improved. IATT is
      not an effective preventive treatment of dermal filler-associated CRAO. The
      authors suggest careful preprocedural patient selection to prevent this
      complication.

PMID- 29378381
TI  - [Antimicrobial activity of ceftolozane/tazobactam against Enterobacteriaceae and
      Pseudomonas aeruginosa in the Czech Republic in 2016].
AB  - OBJECTIVE: Ceftolozane/tazobactam is an antibiotic effective against Gram
      negative bacteria(including Pseudomonas aeruginosa).The study aimed at
      determining the effectiveness of the novel antibiotic in the Czech Republic.
      MATERIAL AND METHODS: The effectiveness of the antibiotic was studied in 16 Czech
      laboratories in 822 Enterobacteriaceae isolates (including AmpC and ESBL
      producers) and P. aeruginosa causing complicated intraabdominal or urinary tract
      infections. Minimum inhibitory concentrations were determined using the Etest.
      With the exception of Citrobacter freundii and Enterobacter cloacae,
      ceftozolane/tazobactam proved to be very effective against Enterobacteriaceae; no
      P. aeruginosa strain was resistant to the antibiotic. CONCLUSION: The results
      confirmed good activity of ceftozolane/tazobactam in vitro against
      Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca,
      Proteus mirabilis) and P. aeruginosa in the Czech Republic.

PMID- 29378382
TI  - [First experience with elbasvir/grazoprevir fixed-dose combination in real-life
      practice in the Czech Republic].
AB  - Hepatitis C virus infection (HCV) is one of the leading causes of chronic liver
      disease worldwide. The new fixed-dose combination of the highly potent second
      wave first generation NS5A inhibitor elbasvir (50 mg) and the second generation
      protease inhibitor grazoprevir (100 mg) is contained in the drug Zepatier. This
      combination is indicated for the treatment of patients chronically infected with
      HCV genotypes 1 or 4. Between June and August 2017, the treatment was initiated
      in 22 patients with chronic viral hepatitis C, with 17 patients being treated in
      the Department of Infectious Diseases University Hospital Brno and five patients
      in the Center of Cardiovascular and Transplant Surgery in Brno. All patients were
      infected with HCV subtype 1b. In all cases, the duration of Zepatier monotherapy
      (without simultaneous ribavirin administration) was 12 weeks. At the moment, only
      preliminary results are available. All 22 patients achieved end-of-treatment
      virologic response. In nine patients, it was already possible to evaluate the
      virologic response at four weeks after the end of treatment, with sustained
      virological response (SVR12) was observed in all these patients. The most common
      complaints were fatigue (3 patients, 14 %) and headache (2.9 %). These problems
      were not serious and did not interfere with normal daily activities of treated
      persons.

PMID- 29378383
TI  - [Concurrent malaria and rickettsiosis in a patient returning from the Republic of
      South Africa].
AB  - Definitive diagnosis and therapy proved challenging in the case of a 60-year-old
      male with malaria and rickettsiosis. Returning travellers who are unwell can
      present practical difficulties in diagnosis and treatment and the focus here is
      on conditions relevant to the Republic of South Africa. Malaria, rickettsiosis
      and Q fever are discussed.

PMID- 29378384
TI  - [Diagnosis and therapy of hepatitis B virus infection: Czech national
      guidelines].
AB  - The new recommendations reflect the increase in knowledge that has been reported
      since the release of previous Czech guidelines in September 2014. The basis for
      these guidelines were the European Association for the Study of the Liver
      guidelines from April 2017. According to qualified estimates, there are 240
      million people with chronic hepatitis B (HBV) infection worldwide. The Czech
      Republic is among the countries with a low prevalence of HBV infection. According
      to the latest seroprevalence study, 0.56 % of the Czech citizens were chronically
      infected with HBV in 2001. A similar study conducted in only two regions of the
      Czech Republic in 2013 showed a prevalence of only 0.064 %. HBV infection can
      lead to serious life-threatening liver damage - fulminant hepatitis, liver
      cirrhosis and hepatocellular carcinoma (HCC). The main goals of treatment are to
      prolong the length of life and improve its quality by preventing the progression
      of chronic hepatitis to cirrhosis, cirrhosis decompensation and development of
      HCC. The goals may be achieved if HBV replication is suppressed in a sustained
      manner. Additional goals are prevention of vertical transmission from mother to
      newborn, inhibition of HBV reactivation and therapy of HBV-related extrahepatic
      manifestations. Generally, there are two different strategies of chronic
      hepatitis B therapy available - treatment with nucleoside or nucleotide
      inhibitors (NIs) or with pegylated interferon alfa. Currently, the vast majority
      of Czech and European patients are treated with NIs. The NIs that have been
      approved for HBV treatment in the European Union include lamivudine, adefovir
      dipivoxil, entecavir (ETV), telbivudin (TBV), tenofovir disoproxil fumarate (TDF)
      and tenofovir alafenamide (TAF). TAF and TBV have not yet been marketed in the
      Czech Republic. The main advantages of treatment with potent NIs with a high
      barrier to resistance (ETV, TDF, TAF) are their predictable high long-term
      antiviral efficacy leading to undetectable HBV DNA levels in the vast majority of
      compliant patients as well as their favorable safety profiles. These drugs can be
      used in any HBV infected patient and represent the only treatment option for
      patients with decompensated liver cirrhosis, liver transplants, extrahepatic HBV
      related manifestations, severe acute hepatitis B or chronic HBV reactivation.

PMID- 29378385
TI  - Novel FOXL2 mutations cause blepharophimosis-ptosis-epicanthus inversus syndrome
      with premature ovarian insufficiency.
AB  - BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a
      malformation of the eyelids. Forkhead Box L2 (FOXL2) is the only gene known to be
      associated with BPES. METHODS: We identified two Han Chinese BPES families with
      premature ovarian insufficiency (POI). Sanger sequencing and in vitro functional
      analysis were performed to identify the genetic cause. RESULTS: Sanger sequencing
      identified two novel mutations (c.462_468del, c.988_989insG) in FOXL2, one in
      each family. The in vitro functional analysis confirmed that both novel mutations
      were associated with impaired transactivation of downstream genes. Specifically,
      the single-base insertion, c.988_989insG, led to subcellular mislocalization and
      aggregation of the encoded protein, which validated the hypothesis that the two
      novel FOXL2 mutations are deleterious and associated with POI in the two BPES
      families. CONCLUSION: The novel mutations identified in the present study will
      enhance the present knowledge of the mutation spectrum of FOXL2. The in vitro
      experiments provide further insights into the molecular mechanism by which the
      two new variants mediate disease pathogenesis and may contribute to elucidating
      the genotype-phenotype correlation between the two novel FOXL2 mutations and POI.

PMID- 29378386
TI  - Stachydrine ameliorates carbon tetrachloride-induced hepatic fibrosis by
      inhibiting inflammation, oxidative stress and regulating MMPs/TIMPs system in
      rats.
AB  - Inflammation and oxidative stress are two crucial factors mediating liver
      fibrosis. Stachydrine (STA) is a naturally occurring compound extracted from a
      medicinal plant Leonuru heterophyllus, which can inhibit the proliferation and
      induce the apoptosis of breast cancer cells, relieve high glucose-induced
      endothelial cell senescence and isoproterenol-induced cardiac hypertrophy, and
      exert antitumor effects. However, its roles in hepatic fibrosis remain largely
      unknown. We aimed to evaluate the effect of STA on carbon tetrachloride (CCl4)
      induced hepatic fibrosis in rats and to elucidate the possible mechanisms. STA
      alleviated the pathological changes caused by CCl4 injection in livers compared
      to the normal liver. Hematoxylin-eosin staining further showed that STA treatment
      remarkably improved the liver histology, as evidenced by mitigated hepatic
      steatosis, necrosis, and fibrotic septa. STA reduced the liver/body weight ratio
      and the serum levels of aminotransferase, aspartate aminotransferase and alkaline
      phosphatase. It also significantly decreased collagen deposition and
      hydroxyproline level. Both mRNA and protein levels of alpha-SMA, alpha1(I)
      procollagen and fibronectin were decreased by STA compared to those of the model
      group. STA significantly inhibited the expressions of inflammatory factors
      interleukin-6 (IL-6), IL-8, IL-1beta, tumor necrosis factor-alpha, inducible
      nitric oxide synthase and cyclooxygenase-2. It suppressed oxidative stress by
      decreasing malondialdehyde level as well as increasing glutathione level and
      enzymatic activities of superoxide dismutase, catalase, glutathione reductase and
      glutathione peroxidase. STA also significantly increased the protein expressions
      of tissue inhibitor of metallopeptidase-1 (TIMP-1) and TIMP-2 but decreased those
      of matrix metalloproteinase-2 (MMP-2) and MMP-9, indicating excessive basement
      membrane in the fibrotic liver. Collectively, STA has potent protective effects
      on the liver, with therapeutic implication for liver fibrosis.

PMID- 29378388
TI  - Limits of endoscopic endonasal transpterygoid approach to cavernous sinus and
      Meckel's cave.
AB  - The endoscopic endonasal approach (EEA) to the ventral skull base has greatly
      increased in popularity over the last two decades. So-called expanded EEA have
      opened corridors to pathology off-midline, including lesions within the cavernous
      sinus and Meckel's cave. A standard EEA exposure into the sphenoid sinus allows
      visualization of the medial cavernous sinus; a transpterygoid approach allows for
      surgical manipulation of the lateral cavernous sinus and Meckel's cave contents.
      Pituitary adenomas, meningiomas, and schwannomas are the most common pathologies
      in this region. This approach to the "front door" of the cavernous sinus and
      Meckel's cave should be considered complementary to traditional craniotomy
      techniques as each have benefits and limitations. Herein we review the published
      literature regarding endoscopic endonasal transpterygoid surgery for pathology in
      the lateral cavernous sinus and Meckel's cave, and the anatomical and functional
      limitations of these approaches.

PMID- 29378389
TI  - Limits of endoscopic endonasal surgery for III ventricle craniopharyngiomas.
AB  - Craniopharyngiomas represent one of the most challenging brain tumors for the
      neurosurgeon. For most of the 20th century, these parasellar lesions have been
      approached via the classic open approaches of neurosurgery such as pterional,
      frontobasal, interhemispheric, and transpetrosal craniotomies. The endoscopic
      endonasal approach to these tumors, rather than craniotomy, has risen in
      popularity over the last two decades. Regardless of approach, a detailed
      knowledge of surgical anatomy and careful preoperative surgical planning are
      essential to achieve good clinical results; iatrogenic morbidity can potentially
      be severe due to hypothalamus, optic apparatus, and/or vascular injuries.
      Especially challenging, and highlighting the limitations of endoscopic endonasal
      surgery, are the tumors that arise primarily from within the third ventricle and
      do not expand the pituitary stalk and suprasellar region or tumors that have
      projected to areas far from the parasellar region as such as the sylvian and
      ambient cisterns. Herein we review the published literature regarding endoscopic
      endonasal surgery for craniopharyngioma, and the anatomical and functional
      limitations therein. The benefits and drawbacks of each surgical approach to this
      deep-seated area are discussed, and a strategy for surgical decision-making
      proposed.

PMID- 29378390
TI  - Stable and Label-Free Fluorescent Probe Based on G-triplex DNA and Thioflavin T.
AB  - G-triplexes have recently been identified as a new kind of DNA structures. They
      perhaps possess specific biological and chemical functions similar as identified
      G-quadruplex but can be formed by shorter G-rich sequences with only three G
      tracts. However, until now, limited G-triplexes sequences have been reported,
      which might be due to the fact that their stability is one of the biggest
      concerns during their functional studies and application research. Herein, we
      found a G-rich sequence (5'-TGGGTAGGGCGGG-3') which can form a stable G-triplex
      (Tm ~ 60  degrees C) at room temperature. The stable G-triplex can combine with
      thioflavin T and function as an efficient fluorescence light-up probe. Comparing
      with the traditional G-quadruplex based probe, this triplex based probe was easy
      to be controlled and excited. Finally, the probe was successfully applied into
      constructing a label-free molecular beacon for miRNA detection. Taking advantage
      of these abilities of the G-triplex based fluorescent probe, the challenges faced
      during designing G-rich sequences based fluorescent biosensors can be efficiently
      solved. These findings provide important information for the future application
      of G-triplex.

PMID- 29378391
TI  - Lithographically Patterned Functional Polymer-Graphene Hybrids for Nanoscale
      Electronics.
AB  - Two-dimensional (2D) materials are believed to hold significant promise in
      nanoscale optoelectronics. While significant progress has been made in this field
      over the past decade, the ability to control charge carrier density with high
      spatial precision remains an outstanding challenge in 2D devices. We present an
      approach that simultaneously addresses the dual issues of charge-carrier doping
      and spatial precision based on a functional lithographic resist that employs
      methacrylate polymers containing zwitterionic sulfobetaine pendent groups for
      noncovalent surface doping of 2D materials. We demonstrate scalable approaches
      for patterning these polymer films via electron-beam lithography, achieving
      precise spatial control over carrier doping for fabrication of high-quality, all
      2D, lateral p-n junctions in graphene. Our approach preserves all of the
      desirable structural and electronic properties of graphene while exclusively
      modifying its surface potential. The functional polymer resist platform and
      concept offers a facile route toward lithographic doping of graphene- and other
      2D material-based optoelectronic devices.

PMID- 29378387
TI  - Depolarizing Effectors of Bradykinin Signaling in Nociceptor Excitation in Pain
      Perception.
AB  - Inflammation is one of the main causes of pathologic pain. Knowledge of the
      molecular links between inflammatory signals and pain-mediating neuronal signals
      is essential for understanding the mechanisms behind pain exacerbation. Some
      inflammatory mediators directly modulate the excitability of pain-mediating
      neurons by contacting the receptor molecules expressed in those neurons. For
      decades, many discoveries have accumulated regarding intraneuronal signals from
      receptor activation through electrical depolarization for bradykinin, a major
      inflammatory mediator that is able to both excite and sensitize pain-mediating
      nociceptor neurons. Here, we focus on the final effectors of depolarization, the
      neuronal ion channels, whose functionalities are specifically affected by
      bradykinin stimulation. Particular G-protein coupled signaling cascades
      specialized for each specific depolarizer ion channels are summarized. Some of
      these ion channels not only serve as downstream effectors but also play critical
      roles in relaying specific pain modalities such as thermal or mechanical pain.
      Accordingly, specific pain phenotypes altered by bradykinin stimulation are also
      discussed. Some members of the effector ion channels are both activated and
      sensitized by bradykinin-induced neuronal signaling, while others only sensitized
      or inhibited, which are also introduced. The present overview of the effect of
      bradykinin on nociceptor neuronal excitability at the molecular level may
      contribute to better understanding of an important aspect of inflammatory pain
      and help future design of further research on the components involved and pain
      modulating strategies.

PMID- 29378392
TI  - Quantitative mRNA Imaging with Dual Channel qFIT Probes to Monitor Distribution
      and Degree of Hybridization.
AB  - Fluorogenic oligonucleotide probes facilitate the detection and localization of
      RNA targets within cells. However, quantitative measurements of mRNA abundance
      are difficult when fluorescence signaling is based on intensity changes because a
      high concentration of unbound probes cannot be distinguished from a low
      concentration of target-bound probes. Here, we introduce qFIT (quantitative
      forced intercalation) probes that allow the detection both of probe-target
      complexes and of unbound probes on separate, independent channels. A surrogate
      nucleobase based on thiazole orange (TO) probes the hybridization status. The
      second channel involves a nonresponsive near-IR dye, which serves as a reporter
      of concentration. We show that the undesirable perturbation of the hybridization
      reporter TO is avoided when the near-IR dye Cy7 is connected by means of short
      triazole linkages in an >=18 nucleotides distance. We used the qFIT probes to
      localize and quantify oskar mRNA in fixed egg chambers of wild-type and mutant
      Drosophila melanogaster by wash-free fluorescence in situ hybridization. The
      measurements revealed a relative 400-fold enrichment of oskar within a 3000 MUm3
      large volume at the posterior pole of stage 8-9 oocytes, which peaked at a
      remarkably high 1.8 MUM local concentration inside 0.075 MUm3 volume units. We
      discuss detection limits and show that the number of oskar mRNA molecules per
      oocyte is independent of the oocyte size, which suggests that the final levels
      are attained already during the onset of oskar localization at stage 8.

PMID- 29378393
TI  - Autochthonous Bioaugmentation-Modified Bacterial Diversity of Phenanthrene
      Degraders in PAH-Contaminated Wastewater as Revealed by DNA-Stable Isotope
      Probing.
AB  - To reveal the mechanisms of autochthonous bioaugmentation (ABA) in wastewater
      contaminated with polycyclic aromatic hydrocarbons (PAHs), DNA-stable-isotope
      probing (SIP) was used in the present study with the addition of an autochthonous
      microorganism Acinetobacter tandoii LJ-5. We found LJ-5 inoculum produced a
      significant increase in phenanthrene (PHE) mineralization, but LJ-5 surprisingly
      did not participate in indigenous PHE degradation from the SIP results. The
      improvement of PHE biodegradation was not explained by the engagement of LJ-5 but
      attributed to the remarkably altered diversity of PHE degraders. Of the major PHE
      degraders present in ambient wastewater ( Rhodoplanes sp., Mycobacterium sp.,
      Xanthomonadaceae sp. and Enterobacteriaceae sp.), only Mycobacterium sp. and
      Enterobacteriaceae sp. remained functional in the presence of strain LJ-5, but
      five new taxa Bacillus, Paenibacillus, Ammoniphilus, Sporosarcina, and
      Hyphomicrobium were favored. Rhodoplanes, Ammoniphilus, Sporosarcina, and
      Hyphomicrobium were directly linked to, for the first time, indigenous PHE
      biodegradation. Sequences of functional PAH-RHDalpha genes from heavy fractions
      further proved the change in PHE degraders by identifying distinct PAH-ring
      hydroxylating dioxygenases between ambient degradation and ABA. Our findings
      indicate a new mechanism of ABA, provide new insights into the diversity of PHE
      degrading communities, and suggest ABA as a promising in situ bioremediation
      strategy for PAH-contaminated wastewater.

PMID- 29378394
TI  - Scalable Production of Few-Layer Boron Sheets by Liquid-Phase Exfoliation and
      Their Superior Supercapacitive Performance.
AB  - Although two-dimensional boron (B) has attracted much attention in electronics
      and optoelectronics due to its unique physical and chemical properties, in-depth
      investigations and applications have been limited by the current synthesis
      techniques. Herein, we demonstrate that high-quality few-layer B sheets can be
      prepared in large quantities by sonication-assisted liquid-phase exfoliation. By
      simply varying the exfoliating solvent types and centrifugation speeds, the
      lateral size and thickness of the exfoliated B sheets can be controllably tuned.
      Additionally, the exfoliated few-layer B sheets exhibit excellent stability and
      outstanding dispersion in organic solvents without aggregates for more than 50
      days under ambient conditions, owing to the presence of a solvent residue shell
      on the B sheet surface that provides excellent protection against air oxidation.
      Moreover, we also demonstrate the use of the exfoliated few-layer B sheets for
      high-performance supercapacitor electrode materials. This as-prepared device
      exhibits impressive electrochemical performance with a wide potential window of
      up to 3.0 V, excellent energy density as high as 46.1 Wh/kg at a power density of
      478.5 W/kg, and excellent cycling stability with 88.7% retention of the initial
      specific capacitance after 6000 cycles. This current work not only demonstrates
      an effective strategy for the synthesis of the few-layer B sheets in a controlled
      manner but also makes the resulting materials promising for next-generation
      optoelectronics and energy storage applications.

PMID- 29378395
TI  - Antibiotics Disturb the Microbiome and Increase the Incidence of Resistance Genes
      in the Gut of a Common Soil Collembolan.
AB  - Gut microbiota make an important contribution to host health but the effects of
      environmental pressures on the gut microbiota of soil fauna are largely
      uncharacterized. Here, we examine the effects of norfloxacin and oxytetracycline
      on the gut microbiome of the common soil collembolan Folsomia candida and
      concomitant changes in the incidence of antibiotic resistance genes (ARGs) in the
      gut and in growth of the collembolan. Exposure to 10 mg antibiotics kg-1 for 2
      weeks significantly inhibited the growth of the collembolan with roughly a 10
      fold decrease in 16S rRNA gene abundance. Antibiotics did alter the composition
      and structure of the collembolan gut microbiome and decreased the diversity of
      the gut bacteria. A decline in the firmicutes/bacteroidetes ratio in the
      antibiotic-treated collembolans may be responsible for the decrease in body
      weight. Exposure to antibiotics significantly increased the diversity and
      abundance of ARGs in the collembolan gut. The Mantel test and Procrustes analysis
      both reveal that ARGs and gut microbiota were significantly correlated with one
      another ( P < 0.05). These results indicate that antibiotics may induce a shift
      in the gut microbiota of nontarget organisms such as soil collembolans and
      thereby affect their growth and enrichment of ARGs.

PMID- 29378396
TI  - Recovery of Macro and Micro-Nutrients by Hydrothermal Carbonization of Septage.
AB  - In this study, septic tank waste (i.e., septage) was hydrothermally carbonized
      (HTC) in order to recover macro and micronutrients, while tracking the fate of
      residual heavy metals. Three different HTC temperatures (i.e., 180, 220, and 260 
      degrees C) at autogenous pressures and two reaction times (i.e., 30 and 120 min)
      were applied on both solid and liquid septages. Hydrochar and HTC process liquids
      were characterized using ICP, CHNS, and UV-vis spectroscopy. Treatment at 260 
      degrees C for 120 min maximized ammonia recovery, producing a liquid with 1400
      mg/L of ammonia. Overall, about 70% of available nitrogen ended up in the liquid
      phase as nitrate or ammonia. Solid hydrochars show potential for fertilizer use,
      with high phosphorus content of 100-130 kg/tonne. It was found that heavy metals
      mainly remained in the solid phase, although the concentrations of heavy metals
      are mostly lower than U.S. EPA regulation for biosolids with the exception of
      selenium.

PMID- 29378397
TI  - En Route to 2-(Cyclobuten-1-yl)-3-(trifluoromethyl)-1H-indole.
AB  - A six-step synthetic route from 4-chloro-2-methylaniline to 5-chloro-2-(cyclobut
      1-en-1-yl)-3-(trifluoromethyl)-1H-indole (1) has been reported. Compound 1a is a
      key impurity of reverse transcriptase inhibitor efavirenz, an important anti
      HIV/AIDS drug. Synthetic challenges, dead ends, and detours are discussed.

PMID- 29378398
TI  - Partnership of Arthrobacter and Pimelobacter in Aerobic Degradation of
      Sulfadiazine Revealed by Metagenomics Analysis and Isolation.
AB  - In this study, metagenomic analyses were combined with cultivation-based
      techniques as a nested approach to identify functionally significant bacteria for
      sulfadiazine biodegradation within enrichment communities. The metagenomic
      investigations indicated that our previously isolated sulfadiazine degrader,
      Arthrobacter sp. D2, and another Pimelobacter bacterium concomitantly occurred as
      most abundant members in the community of an enrichment culture that performed
      complete sulfadiazine mineralization for over two years. Responses of the
      enriched populations to sole carbon source alternation further suggested the
      ability of this Pimelobacter member to grow on 2-aminopyrimidine, the most
      prominent intermediate metabolite of sulfadiazine. Taking advantage of this
      propensity, additional cultivation procedures have enabled the successful
      isolation of Pimelobacter sp. LG209, whose genomic sequences exactly matched that
      of the dominant Pimelobacter bacterium in the sulfadiazine enrichment culture.
      Integration of metagenomic investigations with the physiological characteristics
      of the isolates conclusively demonstrated that the sulfadiazine mineralization in
      a long-running enrichment culture was prominently mediated by primary
      sulfadiazine-degrading specialist strain Arthrobacter sp. D2 in association with
      the 2-aminopyrimidine-degrading partner strain Pimelobacter sp. LG209. Here, we
      provided the first mechanistic insight into microbial interactions in steady
      sulfadiazine mineralization processes, which will help develop appropriate
      bioremediation strategies for sulfadiazine-contaminated hotspot sites.

PMID- 29378399
TI  - Accuracy Comparison of Generalized Born Models in the Calculation of
      Electrostatic Binding Free Energies.
AB  - The need for accurate yet efficient representation of the aqueous environment in
      biomolecular modeling has led to the development of a variety of generalized Born
      (GB) implicit solvent models. While many studies have focused on the accuracy of
      available GB models in predicting solvation free energies, a systematic
      assessment of the quality of these models in binding free energy calculations,
      crucial for rational drug design, has not been undertaken. Here, we evaluate the
      accuracies of eight common GB flavors (GB-HCT, GB-OBC, GB-neck2, GBNSR6, GBSW,
      GBMV1, GBMV2, and GBMV3), available in major molecular dynamics packages, in
      predicting the electrostatic binding free energies ( DeltaDelta Gel) for a
      diverse set of 60 biomolecular complexes belonging to four main classes: protein
      protein, protein-drug, RNA-peptide, and small complexes. The GB flavors are
      examined in terms of their ability to reproduce the results from the Poisson
      Boltzmann (PB) model, commonly used as accuracy reference in this context. We
      show that the agreement with the PB of DeltaDelta Gel estimates varies widely
      between different GB models and also across different types of biomolecular
      complexes, with R2 correlations ranging from 0.3772 to 0.9986. A surface-based
      "R6" GB model recently implemented in AMBER shows the closest overall agreement
      with reference PB ( R2 = 0.9949, RMSD = 8.75 kcal/mol). The RNA-peptide and
      protein-drug complex sets appear to be most challenging for all but one model, as
      indicated by the large deviations from the PB in DeltaDelta Gel. Small neutral
      complexes present the least challenge for most of the GB models tested. The
      quantitative demonstration of the strengths and weaknesses of the GB models
      across the diverse complex types provided here can be used as a guide for
      practical computations and future development efforts.

PMID- 29378400
TI  - Controlling Fundamental Fluctuations for Reproducible Growth of Large Single
      Crystal Graphene.
AB  - The controlled growth of graphene by the chemical vapor deposition method is
      vital for its various applications; however, the reproducibility remains a great
      challenge. Here, using single-crystal graphene growth on a Cu surface as a model
      system, we demonstrate that a trace amount of H2O and O2 impurity gases in the
      reaction chamber is key for the large fluctuation of graphene growth. By
      precisely controlling their parts per million level concentrations, centimeter
      sized single-crystal graphene is obtained in a reliable manner with a maximum
      growth rate up to 190 MUm min-1. The roles of oxidants are elucidated as an
      effective modulator for both graphene nucleation density and growth rate. This
      control is more fundamental for reliable growth of graphene beyond previous
      findings and is expected to be useful for the growth of various 2D materials that
      are also sensitive to trace oxidant impurities.

PMID- 29378402
TI  - Who Is the Rock Miner and Who Is the Hunter? The Use of Heavy-Oxygen Labeled
      Phosphate (P18O4) to Differentiate between C and P Fluxes in a Benzene-Degrading
      Consortium.
AB  - Phosphorus availability and cycling in microbial communities is a key determinant
      of bacterial activity. However, identifying organisms critical to P cycling in
      complex biodegrading consortia has proven elusive. Here we assess a new DNA
      stable isotope probing (SIP) technique using heavy oxygen-labeled phosphate
      (P18O4) and its effectiveness in pure cultures and a nitrate-reducing benzene
      degrading consortium. First, we successfully labeled pure cultures of Gram
      positive Micrococcus luteus and Gram-negative Bradyrhizobium elkanii and
      separated isotopically light and heavy DNA in pure cultures using centrifugal
      analyses. Second, using high-throughput amplicon sequencing of 16S rRNA genes to
      characterize active bacterial taxa (13C-labeled), we found taxa like
      Betaproteobacteria were key in denitrifying benzene degradation and that other
      degrading (nonhydrocarbon) inactive taxa (P18O4-labeled) like Staphylococcus and
      Corynebacterium may promote degradation through production of secondary
      metabolites (i.e., "helper" or "rock miner" bacteria). Overall, we successfully
      separated active and inactive taxa in contaminated soils, demonstrating the
      utility of P18O4-DNA SIP for identifying actively growing bacterial taxa. We also
      identified potential "miner" bacteria that choreograph hydrocarbon degradation by
      other microbes (i.e., the "hunters") without directly degrading contaminants
      themselves. Thus, while several taxa degrade benzene under denitrifying
      conditions, microbial benzene degradation may be enhanced by both direct
      degraders and miner bacteria.

PMID- 29378401
TI  - Epidermis Microstructure Inspired Graphene Pressure Sensor with Random
      Distributed Spinosum for High Sensitivity and Large Linearity.
AB  - Recently, wearable pressure sensors have attracted tremendous attention because
      of their potential applications in monitoring physiological signals for human
      healthcare. Sensitivity and linearity are the two most essential parameters for
      pressure sensors. Although various designed micro/nanostructure morphologies have
      been introduced, the trade-off between sensitivity and linearity has not been
      well balanced. Human skin, which contains force receptors in a reticular layer,
      has a high sensitivity even for large external stimuli. Herein, inspired by the
      skin epidermis with high-performance force sensing, we have proposed a special
      surface morphology with spinosum microstructure of random distribution via the
      combination of an abrasive paper template and reduced graphene oxide. The
      sensitivity of the graphene pressure sensor with random distribution spinosum
      (RDS) microstructure is as high as 25.1 kPa-1 in a wide linearity range of 0-2.6
      kPa. Our pressure sensor exhibits superior comprehensive properties compared with
      previous surface-modified pressure sensors. According to simulation and mechanism
      analyses, the spinosum microstructure and random distribution contribute to the
      high sensitivity and large linearity range, respectively. In addition, the
      pressure sensor shows promising potential in detecting human physiological
      signals, such as heartbeat, respiration, phonation, and human motions of a
      pushup, arm bending, and walking. The wearable pressure sensor array was further
      used to detect gait states of supination, neutral, and pronation. The RDS
      microstructure provides an alternative strategy to improve the performance of
      pressure sensors and extend their potential applications in monitoring human
      activities.

PMID- 29378404
TI  - The Goldilocks Principle in Phase Labeling. Minimalist and Orthogonal Phase
      Tagging for Chromatography-Free Mitsunobu Reaction.
AB  - An inexpensive and chromatography-free Mitsunobu methodology has been developed
      using low molecular weight and orthogonally phase-tagged reagents, a tert-butyl
      tagged highly apolar phosphine, and a water-soluble DIAD analogue. The byproduct
      of the Mitsunobu reactions can be removed by sequential liquid-liquid extractions
      using traditional solvents such as hexanes, MeOH, water, and EtOAc. Owing to the
      orthogonal phase labeling, the spent reagents can be regenerated. This new
      variant of the Mitsunobu reaction promises to provide an alternative and
      complementary solution for the well-known separation problem of the Mitsunobu
      reaction without having to resort to expensive, large molecular weight reagents
      and chromatography.

PMID- 29378403
TI  - Bioorthogonal Masking of Circulating Antibody-TCO Groups Using Tetrazine
      Functionalized Dextran Polymers.
AB  - Pretargeting strategies have gained popularity for the in vivo imaging and
      therapy of cancer by combining antibodies with small molecule radioligands. In
      vivo recombination of both moieties can be achieved using the bioorthogonal
      inverse electron demand Diels-Alder (IEDDA) chemistry between tetrazine (Tz) and
      trans-cyclooctene (TCO). An issue that arises with pretargeting strategies is
      that while part of the antibody dose accumulates at antigen-expressing tumor
      tissue, there is a significant portion of the injected antibody that remains in
      circulation, causing a reduction in target-to-background ratios. Herein, we
      report the development of a novel TCO scavenger, the masking agent DP-Tz. DP-Tz
      is based on Tz-modified dextran polymers (DP, MW = 0.5-2 MDa). Large dextran
      polymers were reported to exhibit low penetration of tumor vasculature and
      appeared nontoxic, nonimmunogenic, and easily modifiable. Our newly developed
      masking agent deactivates the remaining TCO-moieties on the circulating mAbs yet
      does not impact the tumor uptake of the Tz-radioligand. In pretargeting studies
      utilizing a 68Ga-labeled tetrazine radioligand ([68Ga]Ga-NOTA-PEG11-tetrazine),
      DP-Tz constructs (Tz/DP ratios of 62-254) significantly increased TTB ratios from
      0.8 +/- 0.3 (control cohorts) to up to 5.8 +/- 2.3 at 2 h postinjection. Tumor
      tissue delineation in PET imaging experiments employing DP-Tz is significantly
      increased compared to control. Uptake values of other significant organs, such as
      heart, lungs, pancreas, and stomach, were decreased on average by 2-fold when
      using DP-Tz. Overall, pretargeting experiments utilizing DP-Tz showed
      significantly improved tumor delineation, enhanced PET image quality, and reduced
      uptake in vital organs. We believe that this new masking agent is a powerful new
      addition to the IEDDA-based pretargeting tool box and, due to its properties, an
      excellent candidate for clinical translation.

PMID- 29378405
TI  - Surface Chemistry and Spectroscopic Study of a Cholera Toxin B Langmuir
      Monolayer.
AB  - In this article, we explored the surface chemistry properties of a cholera toxin
      B (CTB) monolayer at the air-subphase interface and investigated the change in
      interfacial properties through in situ spectroscopy. The study showed that the
      impact of the blue shift was negligible, suggesting that the CTB molecules were
      minimally affected by the subphase molecules. The stability of the CTB monolayer
      was studied by maintaining the constant surface pressure for a long time and also
      by using the compression-decompression cycle experiments. The high stability of
      the Langmuir monolayer of CTB clearly showed that the driving force of CTB going
      to the amphiphilic membrane was its amphiphilic nature. In addition, no major
      change was detected in the various in situ spectroscopy results (such as UV-vis,
      fluorescence, and IR ER) of the CTB Langmuir monolayer with the increase in
      surface pressure. This indicates that no aggregation occurs in the Langmuir
      monolayer of CTB.

PMID- 29378406
TI  - Uranium Dioxides and Debris Fragments Released to the Environment with Cesium
      Rich Microparticles from the Fukushima Daiichi Nuclear Power Plant.
AB  - Trace U was released from the Fukushima Daiichi Nuclear Power Plant (FDNPP)
      during the meltdowns, but the speciation of the released components of the
      nuclear fuel remains unknown. We report, for the first time, the atomic-scale
      characteristics of nanofragments of the nuclear fuels that were released from the
      FDNPP into the environment. Nanofragments of an intrinsic U-phase were discovered
      to be closely associated with radioactive cesium-rich microparticles (CsMPs) in
      paddy soils collected ~4 km from the FDNPP. The nanoscale fuel fragments were
      either encapsulated by or attached to CsMPs and occurred in two different forms:
      (i) UO2+X nanocrystals of ~70 nm size, which are embedded into magnetite
      associated with Tc and Mo on the surface and (ii) Isometric (U,Zr)O2+X
      nanocrystals of ~200 nm size, with the U/(U+Zr) molar ratio ranging from 0.14 to
      0.91, with intrinsic pores (~6 nm), indicating the entrapment of vapors or
      fission-product gases during crystallization. These results document the
      heterogeneous physical and chemical properties of debris at the nanoscale, which
      is a mixture of melted fuel and reactor materials, reflecting the complex thermal
      processes within the FDNPP reactor during meltdown. Still CsMPs are an important
      medium for the transport of debris fragments into the environment in a respirable
      form.

PMID- 29378407
TI  - Multiple Pathways and Time Scales for Conformational Transitions in apo-Adenylate
      Kinase.
AB  - The open/close transition in adenylate kinase (AK) is regarded as a
      representative example for large-scale conformational transition in proteins, yet
      its mechanism remains unclear despite numerous experimental and computational
      studies. Using extensive (~50 MUs) explicit solvent atomistic simulations and
      Markov state analysis, we shed new lights on the mechanism of this transition in
      the apo form of AK. The closed basin of apo AK features an open NMP domain while
      the LID domain closes and rotates toward it. Therefore, although the computed
      structural properties of the closed ensemble are consistent with previously
      reported FRET and PRE measurements, our simulations suggest that NMP closure is
      likely to follow AMP binding, in contrast to the previous interpretation of FRET
      and PRE data that the apo state was able to sample the fully closed conformation
      for "ligand selection". The closed state ensemble is found to be kinetically
      heterogeneous; multiple pathways and time scales are associated with the
      open/close transition, providing new clues to the disparate time scales observed
      in different experiments. Besides interdomain interactions, a novel mutual
      information analysis identifies specific intradomain interactions that correlate
      strongly to transition kinetics, supporting observations from previous chimera
      experiments. While our results underscore the role of internal domain properties
      in determining the kinetics of open/close transition in apo AK, no evidence is
      observed for any significant degree of local unfolding during the transition.
      These observations about AK have general implications to our view of
      conformational states, transition pathways, and time scales of conformational
      changes in proteins. The key features and time scales of observed transition
      pathways are robust and similar from simulations using two popular fixed charge
      force fields.

PMID- 29378408
TI  - Small Molecule Inhibitors of the PCSK9.LDLR Interaction.
AB  - The protein-protein interaction between proprotein convertase subtilisin/kexin
      type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) is a relatively new,
      and extremely important, validated therapeutic target for treatment and
      prevention of heart disease. Experts in the area agree that the first small
      molecules to disrupt PCSK9.LDLR would represent a milestone in this field, yet
      few credible leads have been reported. This paper describes how side-chain
      orientations in preferred conformations of carefully designed chemotypes were
      compared with LDLR side chains at the PCSK9.LDLR interface to find molecules that
      would mimic interface regions of LDLR. This approach is an example of the
      procedure called EKO (Exploring Key Orientations). The guiding hypothesis on
      which EKO is based is that good matches indicate the chemotypes bearing the same
      side chains as the protein at the sites of overlay have the potential to disrupt
      the parent protein-protein interaction. In the event, the EKO procedure and one
      round of combinatorial fragment-based virtual docking led to the discovery of
      seven compounds that bound PCSK9 (SPR and ELISA) and had a favorable outcome in a
      cellular assay (hepatocyte uptake of fluorescently labeled low-density
      lipoprotein particles) and increased the expression LDLR on hepatocytes in
      culture. Three promising hit compounds in this series had dissociation constants
      for PCSK9 binding in the 20-40 MUM range, and one of these was modified with a
      photoaffinity label and shown to form a covalent conjugate with PCSK9 on
      photolysis.

PMID- 29378409
TI  - Artemisinin-Loaded Mesoporous Nanoplatform for pH-Responsive Radical Generation
      Synergistic Tumor Theranostics.
AB  - The development of novel and effective cancer treatments will greatly contribute
      to prolonging and improving patient lives. In this study, a multifunctional
      nanoplatform was designed and developed based on mesoporous NiO (mNiO)
      nanoparticles and terbium complexes as an artemisinin (ART) vehicle, a T2
      weighted contrast agent, and a luminescence imaging probe. mNiO is a novel pH
      responsive material that can degrade and release nickel ions (Ni2+) in an acidic
      tumor microenvironment. The endoperoxide bridge bond in the structure of ART
      tends to react with Ni2+ to produce radicals that can kill tumor cells. On the
      basis of its excellent near-infrared absorbance, mNiO can also be considered as a
      novel photothermal conversion agent for cancer photothermal therapy (PTT).
      Compared with free ART or PTT only, this novel agent showed remarkably enhanced
      antitumor activity in cultured cells and in tumor mice models, owing to the
      hypoxic tumor microenvironment impelling synergistic therapeutic action. These
      results provide a novel way of using a promising natural drug-based nanoplatform
      for synergistic therapy of tumors.

PMID- 29378410
TI  - Kinetics of Dissolution of an Amorphous Solid.
AB  - The kinetics of dissolution of an amorphous solid is studied using a simple model
      of a glass that captures with reasonable accuracy the dynamic heterogeneities
      associated with the relaxation of an amorphous material at low temperatures. The
      intrinsic dissolution rate is shown to be proportional to the concentration of
      surface particles kinetically able to exchange with the solvent, independent of
      temperature or the thermal history of the glass. The morphology of the dissolving
      surface is described, and the possibility of using surface etching to image
      dynamic heterogeneities is explored.

PMID- 29378411
TI  - Complexity of Advanced Glycation End Products in Foods: Where Are We Now?
AB  - Recent clinical trials indicate that consumption of dietary advanced glycation
      end products (AGEs) may promote the development of major chronic diseases.
      However, the outcomes of human studies have proven inconclusive as a result of
      estimates of the total AGE intake being taken with a single AGE in most of the
      studies. In this perspective, we summarized the major types of AGEs derived from
      proteins, nucleic acids, and phospholipids during food processing and suggested a
      panel of AGEs as markers to better measure the intake of total dietary AGEs in
      human studies.

PMID- 29378412
TI  - Exploring Electronic Structure and Order in Polymers via Single-Particle
      Microresonator Spectroscopy.
AB  - PEDOT: PSS, a transparent electrically conductive polymer, finds widespread use
      in electronic devices. While empirical efforts have increased conductivity, a
      detailed understanding of the coupled electronic and morphological landscapes in
      PEDOT:PSS has lagged due to substantial structural heterogeneity on multiple
      length-scales. We use an optical microresonator-based absorption spectrometer to
      perform single-particle measurements, providing a bottom-up examination of
      electronic structure and morphology ranging from single PEDOT:PSS polymers to
      nascent films. Using single-particle spectroscopy with complementary theoretical
      calculations and ultrafast spectroscopy, we demonstrate that PEDOT:PSS displays
      bulk-like optical response even in single polymers. We find highly ordered PEDOT
      assemblies with long-range ordering mediated by the insulating PSS matrix and
      reveal a preferential surface orientation of PEDOT nanocrystallites absent in
      bulk films with implications for interfacial electronic communication. Our single
      particle perspective provides a unique window into the microscopic structure and
      electronic properties of PEDOT:PSS.

PMID- 29378413
TI  - Hand-Held Photometer for Instant On-Spot Quantification of Nucleic Acids,
      Proteins, and Cells.
AB  - This paper presents a novel hand-held photometer, termed "Photopette", for on
      spot absorbance measurements of biochemical analytes. The Photopette is a
      multicomponent, highly portable device with an overall weight of 160 g, which
      fits within 202 mm * 47 mm * 42 mm. Designed in the form factor of a
      micropipette, Photopette integrates a photodiode detector with light emitting
      diodes (LEDs) to form a highly customizable photometer which supports a wide
      variety of applications within the wavelengths between 260 and 1050 nm. A dual
      purpose disposable reflective tip was designed to act as a sample holder and a
      light-reflecting system, which is in stark contrast to the operation of
      mainstream spectrophotometers and photometers. Small volume analytes may be
      measured with low sample loss using this proprietary CuveTip. A user-friendly
      software application running on smart devices was developed to control and read
      the values from Photopette via a low-energy Bluetooth link. This one-step
      strategy allows measurements on-spot without sample transfer, minimizing cross
      contamination and human error. The results reported in this paper demonstrate
      Photopette's great potential to quantify DNA, direct protein, and cell density
      directly within the laminar flow hood. Results are compared with a Nanodrop 2000c
      spectrophotometer, a mainstream spectrophotometer for small-volume measurements.

PMID- 29378414
TI  - The E15R Point Mutation in Scorpion Toxin Cn2 Uncouples Its Depressant and
      Excitatory Activities on Human NaV1.6.
AB  - We report the chemical synthesis of scorpion toxin Cn2, a potent and highly
      selective activator of the human voltage-gated sodium channel NaV1.6. In an
      attempt to decouple channel activation from channel binding, we also synthesized
      the first analogue of this toxin, Cn2[E15R]. This mutation caused uncoupling of
      the toxin's excitatory and depressant activities, effectively resulting in a
      NaV1.6 inhibitor. In agreement with the in vitro observations, Cn2[E15R] is
      antinociceptive in mouse models of NaV1.6-mediated pain.

PMID- 29378415
TI  - Severe Toxicity in Nonhuman Primates and Piglets with Systemic High-Dose
      Administration of Adeno-Associated Virus Serotype 9-Like Vectors: Putting
      Patients First.

PMID- 29378416
TI  - Wellness-Promoting Practices Through Girl Scouts: A Pragmatic Superiority
      Randomized Controlled Trial With Additional Dissemination.
AB  - PURPOSE: To evaluate the effectiveness of in-person versus online Girl Scout
      leader wellness training for implementation of wellness-promoting practices
      during troop meetings (phase I) and to assess training adoption and current
      practices across the council (phase II). DESIGN: Pragmatic superiority trial
      (phase 1) followed by serial cross-sectional study (phase II). SETTING: Girl
      Scout troop meetings in Northeast Kansas. PARTICIPANTS: Eighteen troop leaders
      from 3 counties (phase 1); 113 troop leaders from 7 counties (phase II).
      INTERVENTION: Phase I: Troop leaders attended 2 wellness training sessions (first
      in groups, second individually), wherein leaders set wellness-promoting practice
      implementation goals, self-monitored progress, and received guidance and
      resources for implementation. Leaders received the intervention in person or
      online. MEASURES: Phase I: At baseline and postintervention, leaders completed a
      wellness-promoting practice implementation questionnaire assessing practices
      during troop meetings (max score = 11). Phase II: Leaders completed a survey
      about typical troop practices and interest in further training. ANALYSIS: Phase
      I: Generalized linear mixed modeling. RESULTS: Phase I: In-person training
      increased wellness-promoting practice implementation more than online training
      (in person = 2.1 +/- 1.8; online = 0.2 +/- 1.2; P = .022). Phase II: Fifty-six
      percent of leaders adopted the training. For 8 of 11 wellness categories, greater
      than 50% of leaders employed wellness-promoting practices. CONCLUSION: In-person
      training was superior to online training for improvements in wellness-promoting
      practices. Wellness training was adopted by the majority of leaders across the
      council.

PMID- 29378417
TI  - Epigenetic Modifications Following Noxious Stimuli in Infants.
AB  - PURPOSE: To recruit healthy full- and preterm infants into genetic research and
      determine the effectiveness of a noninvasive DNA sampling technique for comparing
      epigenetic modifications. BACKGROUND: Noxious stimuli during a vulnerable period
      of infant neuronal plasticity may trigger long-term epigenetic changes affecting
      neurodevelopment, pain modulation, and reactivity. Recognizing epigenetic pain
      findings is problematic because parents are reluctant to enroll newborns into
      genetic research. METHODS: Design: Within-subject change over time candidate-gene
      DNA methylation association study. Setting/ sample: Urban teaching hospital's
      neonatal intensive care unit and newborn nursery. Convenience sample of healthy
      full- (>37 weeks, n = 6) and preterm (<37 weeks, n = 6) infants. PROCEDURE:
      Parents participated in a genetic presentation prior to informed consent. Infant
      buccal saliva was collected after admission to the unit and prior to discharge.
      ANALYSIS: The methylation pattern at the 5' end of u-opioid receptor gene (
      OPRM1) was examined. DNA was treated with bisulfite to convert all cytosines to
      uracil residues, leaving methylated cytosines unchanged. Sequencing of untreated
      and bisulfite-converted DNA was carried out. The sequences of unconverted and
      bisulfite-converted DNA were aligned with ClustalW, fidelity of the polymerase
      chain reaction and the sequencing reaction evaluated, and the methylation pattern
      identified. RESULTS: Recruitment and assessment of a noninvasive DNA sampling
      technique for comparing epigenetic modifications were successful; however, infant
      stress did not produce a change in OPRM1 methylation expression. RELEVANCE: This
      study established the feasibility of recruiting healthy full-term infants into
      genetic research and the effectiveness of noninvasive DNA sampling for comparing
      epigenetic modification in infants.

PMID- 29378418
TI  - CPX-351: changing the landscape of treatment for patients with secondary acute
      myeloid leukemia.
AB  - Multiple novel therapeutic agents against acute myeloid leukemia (AML) have been
      evaluated in the past several decades without meaningful clinical improvement in
      outcomes, especially for AML patients age >=60, where the overall incidence of
      AML is highest. Therapeutic options mainly consist of hypomethylating agents,
      ongoing clinical trials and, less commonly, intensive cytotoxic chemotherapy. CPX
      351, a novel liposomal formulation which encapsulates cytarabine and daunorubicin
      in 5:1 molar ratio, has shown promising efficacy, leading to recent US FDA
      approval for front-line therapy for patients with therapy-related AML and AML
      with myelodysplasia-related changes based on a large multicenter Phase III
      clinical trial. This review summarizes the clinical development of CPX-351 as
      induction therapy.

PMID- 29378419
TI  - Clinical importance of eflornithine (alpha-difluoromethylornithine) for the
      treatment of malignant gliomas.
AB  - This review covers the literature between 1989 and 2007 on studies relevant to
      the neuro-oncology usage of eflornithine (alpha-difluoromethylornithine), an oral
      agent that irreversibly inhibits the enzyme ornithine decarboxylase. It covers
      the use of eflornithine, alone or in combination, to treat high-grade gliomas. In
      addition, we provide an update on overall survival from The University of Texas
      MD Anderson Cancer Center Community Clinical Oncology Program and Clinical Trials
      Data Office that demonstrates a meaningful benefit in overall survival for
      eflornithine as a single agent and in combination with nitrosourea-based
      therapies for anaplastic gliomas. We also provide a framework for understanding
      the basis and study design of the ongoing pivotal, registrational Phase III
      multicenter trial for recurrent/progressive anaplastic astrocytoma.

PMID- 29378420
TI  - Embolic Protection Device in Asymptomatic Carotid Stenosis.

PMID- 29378421
TI  - Early animal model evaluation of an implantable contrast agent to enhance
      magnetic resonance imaging of arterial bypass vein grafts.
AB  - Background Non-invasive monitoring of autologous vein graft (VG) bypass grafts is
      largely limited to detecting late luminal narrowing. Although magnetic resonance
      imaging (MRI) delineates vein graft intima, media, and adventitia, which may
      detect early failure, the scan time required to achieve sufficient resolution is
      at present impractical. Purpose To study VG visualization enhancement in vivo and
      delineate whether a covalently attached MRI contrast agent would enable quicker
      longitudinal imaging of the VG wall. Material and Methods Sixteen 12-week-old
      male C57BL/6J mice underwent carotid interposition vein grafting. The inferior
      vena cava of nine donor mice was treated with a gadolinium
      diethylenetriaminepentaacetic acid (Gd-DTPA)-based contrast agent, with control
      VGs labeled with a vehicle. T1-weighted (T1W) MRI was performed serially at
      postoperative weeks 1, 4, 12, and 20. A portion of animals was sacrificed for
      histopathology following each imaging time point. Results MRI signal-to-noise
      ratio (SNR) and contrast-to-noise ratio (CNR) were significantly higher for
      treated VGs in the first three time points (1.73 * higher SNR, P = 0.0006, and
      5.83 * higher CNR at the first time point, P = 0.0006). However, MRI signal
      enhancement decreased consistently in the study period, to 1.29 * higher SNR and
      2.64 * higher CNR, by the final time point. There were no apparent differences in
      graft morphometric analyses in Masson's trichrome-stained sections. Conclusion A
      MRI contrast agent that binds covalently to the VG wall provides significant
      increase in T1W MRI signal with no observed adverse effects in a mouse model.
      Further optimization of the contrast agent to enhance its durability is required.

PMID- 29378422
TI  - The Gestalt of functioning in autism spectrum disorder: Results of the
      international conference to develop final consensus International Classification
      of Functioning, Disability and Health core sets.
AB  - Autism spectrum disorder is associated with diverse social, educational, and
      occupational challenges. To date, no standardized, internationally accepted tools
      exist to assess autism spectrum disorder-related functioning. World Health
      Organization's International Classification of Functioning, Disability and Health
      can serve as foundation for developing such tools. This study aimed to identify a
      comprehensive, a common brief, and three age-appropriate brief autism spectrum
      disorder Core Sets. Four international preparatory studies yielded in total 164
      second-level International Classification of Functioning, Disability and Health
      candidate categories. Based on this evidence, 20 international autism spectrum
      disorder experts applied an established iterative decision-making consensus
      process to select from the candidate categories the most relevant ones to
      constitute the autism spectrum disorder Core Sets. The consensus process
      generated 111 second-level International Classification of Functioning,
      Disability and Health categories in the Comprehensive Core Set for autism
      spectrum disorder-one body structure, 20 body functions, 59 activities and
      participation categories, and 31 environmental factors. The Common Brief Core Set
      comprised 60 categories, while the age-appropriate core sets included 73
      categories in the preschool version (0- to 5-year-old children), 81 in the school
      age version (6- to 16-year-old children and adolescents), and 79 in the older
      adolescent and adult version (?17-year-old individuals). The autism spectrum
      disorder Core Sets mark a milestone toward the standardized assessment of autism
      spectrum disorder-related functioning in educational, administrative, clinical,
      and research settings.

PMID- 29378423
TI  - Receipt of Vasopressors Is Positively Associated With the Length of the Actively
      Dying Process in Hospitalization.
AB  - BACKGROUND: End-of-life care is important in general hospitalization care.
      However, the clinical impact of using vasopressors on the length of the actively
      dying process is still controversial. METHODS: We reviewed patients who were
      hospitalized in general wards and died before discharge. We classified the
      patients into 2 groups: those who received vasopressors (RVs) and those who did
      not receive vasopressors (NRV). We analyzed the factors associated with the
      length of hospital stay (LOS) and the length of the actively dying process.
      RESULTS: In all, 745 participants, 10.01% of all admitted patients, were
      analyzed. Of them, 225 patients were RV group, and the remaining 520 were NRV
      group. Age and gender were comparable in the 2 groups. The use of vasopressors
      was associated with an admission diagnosis of sepsis and absence of Do-Not
      Resuscitate consent and parenteral use of morphine. In multivariable analysis, a
      high Barthel index score, the absence of cancer and cardiopulmonary resuscitation
      (CPR), and no receipt of vasopressors were independent factors for LOS. For the
      length of the actively dying process, a longer duration of inotropic agent, the
      receipt of vasopressors, and the absence of CPR were independent factors.
      CONCLUSION: In-hospital mortality is not uncommon during hospitalization in a
      general ward. The length of the actively dying process is extended by the use of
      vasopressors. Further prospective study is required for cautious evaluation of
      the pros and cons of using vasopressors at the end of life during
      hospitalization.

PMID- 29378424
TI  - Anticipating Needs at End of Life in Narratives Related by People Living With
      HIV/AIDS in Appalachia.
AB  - As part of a mixed methods study determining end-of-life and advanced care
      planning needs in southern Appalachia, a narrative analysis was done of stories
      told in interviews of 8 selected participants using transcript data. Narratives
      were fraught with contradiction and paradox. Tensions were evident about living
      in Appalachia, the Bible Belt, and an area wherein distances are long and
      community rejection can occur as news travels quickly. The primary finding was
      that stigma, from several sources, and shrinking circles of social support for
      people living with HIV/AIDS, all of whom were in treatment, combined to create a
      sense of solitariness. Narratives were fraught with tensions, contradictions, and
      paradoxes. Living in Appalachia, the Bible Belt, and an area wherein distances
      are long and community rejection can occur as news travels quickly. The rejection
      based religiously based stigma was often predicated on stereotypes about sexual
      behavior and illicit drug use. Diagnosis was a key turning point after which many
      spiraled downward financially and socially. Implications for research and
      advanced care planning are included.

PMID- 29378425
TI  - Developing a tool to support diagnostic delivery of dementia.
AB  - It is increasingly recognised that there are challenges affecting the current
      delivery of dementia diagnoses. Steps are required to address this. Current good
      practice guidelines provide insufficient direction and interventions from other
      healthcare settings do not appear to fully translate to dementia care settings.
      This project has taken a sequential two-phase design to developing a tool
      specific to dementia diagnostic delivery. Interviews with 14 participants
      explored good diagnostic delivery. Thematic analysis produced key themes
      (overcoming barriers, navigation of multiple journeys and completing overt and
      covert tasks) that were used to inform the design of a tool for use by
      clinicians, patients and companions. The tool was evaluated for acceptability in
      focused group discussions with 13 participants, which indicated a desire to use
      the tool and that it could encourage good practice. Adaptations were highlighted
      and incorporated to improve acceptability. Future research is now required to
      further evaluate the tool.

PMID- 29378426
TI  - Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous
      Administration of an Adeno-Associated Virus Vector Expressing Human SMN.
AB  - Neurotropic adeno-associated virus (AAV) serotypes such as AAV9 have been
      demonstrated to transduce spinal alpha motor neurons when administered
      intravenously (i.v.) at high doses. This observation led to the recent successful
      application of i.v. AAV9 delivery to treat infants with spinal muscular atrophy,
      an inherited deficiency of the survival of motor neuron (SMN) protein
      characterized by selective death of lower motor neurons. To evaluate the
      efficiency of motor neuron transduction with an AAV9 variant (AAVhu68) using this
      approach, three juvenile nonhuman primates (NHPs; aged 14 months) and three
      piglets (aged 7-30 days) were treated with an i.v. injection of an AAVhu68 vector
      carrying a human SMN transgene at a dose similar to that employed in the spinal
      muscular atrophy clinical trial. Administration of 2 * 1014 genome copies per
      kilogram of body weight resulted in widespread transduction of spinal motor
      neurons in both species. However, severe toxicity occurred in both NHPs and
      piglets. All three NHPs exhibited marked transaminase elevations. In two NHPs,
      the transaminase elevations resolved without clinical sequelae, while one NHP
      developed acute liver failure and shock and was euthanized 4 days after vector
      injection. Degeneration of dorsal root ganglia sensory neurons was also observed,
      although NHPs exhibited no clinically apparent sensory deficits. There was no
      correlation between clinical findings and T-cell responses to the vector capsid
      or transgene product in NHPs. Piglets demonstrated no evidence of hepatic
      toxicity, but within 14 days of vector injection, all three animals exhibited
      proprioceptive deficits and ataxia, which profoundly impaired ambulation and
      necessitated euthanasia. These clinical findings correlated with more severe
      dorsal root ganglia sensory neuron lesions than those observed in NHPs. The liver
      and sensory neuron findings appear to be a direct consequence of AAV transduction
      independent of an immune response to the capsid or transgene product. The present
      results and those of another recent study utilizing a different AAV9 variant and
      transgene indicate that systemic and sensory neuron toxicity may be general
      properties of i.v. delivery of AAV vectors at high doses, irrespective of the
      capsid serotype or transgene. Preclinical and clinical studies involving high
      systemic doses of AAV vectors should include careful monitoring for similar
      toxicities.

PMID- 29378427
TI  - Ultra-obligatory running among ultramarathon runners.
AB  - Participants in the Ultrarunners Longitudinal TRAcking (ULTRA) Study were asked
      to answer "yes" or "no" to the question "If you were to learn, with absolute
      certainty, that ultramarathon running is bad for your health, would you stop your
      ultramarathon training and participation?" Among the 1349 runners, 74.1% answered
      "no". Compared with those answering "yes", they were younger (p < 0.0001), less
      likely to be married (p = 0.019), had less children (p = 0.0095), had a lower
      health orientation (p < 0.0001) though still high, and higher personal goal
      achievement (p = 0.0066), psychological coping (p < 0.0001) and life meaning (p =
      0.0002) scores on the Motivations of Marathoners Scales. Despite a high health
      orientation, most ultramarathon runners would not stop running if they learned it
      was bad for their health as it appears to serve their psychological and personal
      achievement motivations and their task orientation such that they must perceive
      enhanced benefits that are worth retaining at the risk of their health.

PMID- 29378428
TI  - Determination of Lentiviral Infectious Titer by a Novel Droplet Digital PCR
      Method.
AB  - Lentivirus is one of the best vehicles in delivering exogenous genes for
      therapeutics. Prior to application, it is very important to determine the
      infectious titer, which measures only mature virus capable of infecting target
      cells. Quantitative polymerase chain reaction (PCR) and fluorescence-activated
      cell sorting are commonly used for determination of infectious titer. This study
      introduces a new method based on Droplet Digital PCR (ddPCR), a recently
      developed PCR technology that quantifies the absolute amount of target DNA in the
      reaction. In this study, the dynamic range, Limit of Quantification (LOQ), and
      data acceptance criteria for ddPCR are defined against lentiviral sequence. ddPCR
      performance is also compared to established FACS and qPCR methods. This work not
      only demonstrates the feasibility of ddPCR in determining lentiviral infectious
      titer, but provides a detailed method that can be easily adapted by the
      scientific community.

PMID- 29378430
TI  - The potential role of insulin-like growth factor-1 and zinc in brain growth of
      autism spectrum disorder children.

PMID- 29378429
TI  - Extrinsic and Intrinsic Help-Seeking Motivation in the Assessment of Cognitive
      Decline.
AB  - Diagnostic assessments for dementia include the evaluation of subjective memory
      impairment, dementia worries, or depressive symptoms. Data on the predictive
      value of these factors remain unclear, and varying help-seeking behavior may
      contribute to this finding. We investigate whether differentiating help-seeking
      motivation from other psychological factors associated with cognitive impairment
      would enhance the prediction of diagnostic outcomes in a memory clinic. We
      obtained information on help-seeking motivation from 171 patients who underwent
      routine diagnostic assessments. Utilizing a discriminant correspondence analysis,
      our results indicate that extrinsic motivation increases the likelihood of
      receiving a dementia diagnosis, whereas depression or the duration of deficits
      carries discriminatory information to further guide the differentiation of
      prodromal dementia. Recognizing motivational aspects of help-seeking behavior can
      complement the clinical evaluation of cognitive performance.

PMID- 29378431
TI  - Evaluating the occurrence of cryptic invasions of a rocky shore barnacle,
      Semibalanus cariosus, between the north-eastern Pacific and Japan.
AB  - Many coastal barnacles are introduced to non-native regions. However, data are
      lacking on cryptic invasion, which is defined as an invasion that remains
      unrecognised because the invader is mistaken for a native or previously
      introduced species or clade. In this work, cryptic invasions of an intertidal
      barnacle, Semibalanus cariosus, between Japan and the north-eastern Pacific were
      evaluated based on population genetic analyses. A significant genetic
      differentiation was found between the Japanese and north-eastern Pacific
      populations, suggesting a limited introduction of non-native genotypes between
      these regions. Haplotype frequencies did not differ significantly between the
      past (museum samples collected in 1971 from Hokkaido, Japan) and present Japanese
      populations, implying the rare occurrence of human-mediated migration from the
      north-eastern Pacific to Japan. Migrate-n analysis revealed a low level of
      directional gene flow in S. cariosus from the north-eastern Pacific to Japan,
      possibly by natural stepping-stone dispersal via directional water currents or
      human-mediated transport.

PMID- 29378432
TI  - Nanocarrier for levodopa Parkinson therapeutic drug; comprehensive benserazide
      analysis.
AB  - Loss of dopamine-secreting neurons in the midbrain causes Parkinson's disease. L
      DOPA, the precursor to the neurotransmitters dopamine, crosses vast majority of
      physiological and biochemical barriers that dopamine cannot. But most levodopa is
      decarboxylated to dopamine before it reaches the brain. This causes to little
      therapeutic gain with strong peripheral side effects. Benserazide is an
      irreversible inhibitor of peripheral aromatic L-amino acid decarboxylase that
      prevents the breakdown of levodopa in the bloodstream. The challenges are to
      increase the therapeutic efficiency, the bioavailability and decreasing the
      unfavourable side effects of Levodopa drug. Biocompatible nano-sized drug
      carriers could address these challenges at molecular level. Thus calculations of
      drug loading ability of acid-functionalized CNT for the benserazide as a nanodug
      carrier complex for L-DOPA were performed. In this regard, evaluation of all
      adsorption features of the most stable conformer of benserazide molecule onto
      carboxylated carbon nanotube is critical. To determine the minimum energy
      conformer of benserazide, the molecular structure and conformational analysis of
      512 possible conformers have been subjected to first principle quantum mechanical
      calculations. Our work established a novel and easy-to-make formulation of
      benserazide/carboxylated CNT conjugate with extremely high drug loading
      efficiency of Levodopa for Parkinson disease treatment.

PMID- 29378433
TI  - Passive delivery of protein drugs through transdermal route.
AB  - Skin is the largest external organ in the human body but its use for therapeutic
      purposes has been minimal. Stratum corneum residing on the uppermost layer of the
      skin provides a tough barrier to transport the drugs across the skin. Very small
      group of drugs sharing Lipinski properties, i.e. drugs having molecular weight
      not larger than 500 Da, having high lipophilicity and optimum polarity are
      fortunate enough to be used on skin therapeutics. But, at a time where modern
      therapeutics is slowly shifting from use of small molecular drugs towards the use
      of macromolecular therapeutic agents such as peptides, proteins and nucleotides
      in origin, skin therapeutics need to be evolved accordingly to cater the delivery
      of these agents. Physical technologies like iontophoresis, laser ablation, micro
      needles and ultrasound, etc. have been introduced to enhance skin permeability.
      But their success is limited due to their complex working mechanisms and
      involvement of certain irreversible skin damage in some or other way. This review
      therefore explores the delivery strategies for transport of mainly peptide and
      protein drugs that do not involve any injuries (non-invasive) to the skin termed
      as passive delivery techniques. Chemical enhancers, nanocarriers, certain
      biological peptides and miscellaneous approaches like prodrugs are also
      thoroughly reviewed for their applications in protein delivery.

PMID- 29378434
TI  - TLC-bioautography directed isolation of antibacterial compounds from active
      fractionation of Ferula ferulioides.
AB  - A novel optimised isolation method, TLC-bioautography, was evaluated and utilised
      in this research. Antibacterial compounds which were isolated from the
      dichloromethane extract of Ferula ferulioides (Steud.) Korovin were detected by
      means of the method. Their structures were elucidated by extensive spectral and
      chemical methods. Their antibacterial activities against drug-resistant
      Staphylococcus aureus (S. aureus) strains were evaluated with broth microdilution
      method, and the results proved that TLC-bioautography was an effective and highly
      efficient way to screen natural compounds from plant extracts against drug
      resistant strains.

PMID- 29378435
TI  - Measuring emotion socialization in families affected by pediatric cancer:
      Refinement and reduction of the Parents' Beliefs about Children's Emotions
      questionnaire.
AB  - The aim of this study is to conduct a multimethod psychometric reduction in the
      Parents' Beliefs about Children's Emotions (PBCE) questionnaire using an item
      response theory framework with a pediatric oncology sample. Participants were 216
      pediatric oncology caregivers who completed the PBCE. The PBCE contains 105 items
      (11 subscales) rated on a 6-point Likert-type scale. We evaluated the PBCE
      subscale performance by applying a partial credit model in WINSTEPS. Sixty-six
      statistically weak items were removed, creating a 44-item PBCE questionnaire with
      10 subscales and 3 response options per item. The refined scale displayed good
      psychometric properties and correlated .910 with the original PBCE. Additional
      analyses examined dimensionality, item-level (e.g. difficulty), and person-level
      (e.g. ethnicity) characteristics. The refined PBCE questionnaire provides better
      test information, improves instrument reliability, and reduces burden on
      families, providers, and researchers. With this improved measure, providers can
      more easily identify families who may benefit from psychosocial interventions
      targeting emotion socialization. The results of the multistep approach presented
      should be considered preliminary, given the limited sample size.

PMID- 29378436
TI  - Repair of Morgagni hernia and ventricular septal defect through sternotomy.
AB  - We report a case of Morgagni hernia occupying the anterior mediastinum and right
      hemithorax in a male infant with Down syndrome, who also had a perimembranous
      ventricular septal defect. Through a median sternotomy, the hernia sac was freed
      from the right pleura, and the pericardium was opened to reduce its contents
      (colon) into the abdomen. The diaphragmatic defect was closed with Prolene mesh
      and the hernia sac was used to reinforce the diaphragmatic defect. Finally, the
      pericardium was opened and the ventricular septal defect was closed with a
      polytetrafluoroethylene patch through a right atriotomy after instituting
      cardiopulmonary bypass.

PMID- 29378437
TI  - Pierre-Marie-Bamberger syndrome and solitary fibrous tumor: a rare association.
AB  - A solitary fibrous tumor originates in the pleura with variable degrees of
      invasion. Hypertrophic osteoarthropathy, known as Pierre-Marie-Bamberger
      syndrome, is characterized by clubbing of the fingers due to bone surface and
      soft tissue calcification, historically known as a bronchogenic carcinoma
      paraneoplastic syndrome; however, a few cases have been associated with solitary
      fibrous tumors. We describe the case of a 38-year-old woman who presented with
      clubbing of the fingers. Studies revealed an intrathoracic fibrous tumor that was
      successfully treated with improvement in symptoms.

PMID- 29378438
TI  - Editorial.

PMID- 29378440
TI  - Time burden of caring and depression among parents of individuals with cerebral
      palsy.
AB  - PURPOSE: The presence of an individual with disability in a family affects the
      whole family. Families of individuals with cerebral palsy (CP) experience
      increased psychological anxiety and financial problems; specifically, parents
      tend to feel time pressure and struggle to maintain their social and cultural
      activities. METHODS: t-Tests and ANOVA with post hoc Tukey tests were used to
      compare caregiving time, time pressure, and depression between parents.
      Multivariate logistic regression analysis was used to examine the effect of
      caregiving time and time pressure on depression in parents. RESULTS: Regarding
      depression, 58 (38.2%) respondents scored >=16 on the Center for Epidemiological
      Studies - Depression scale. Respondents supporting a preschool child spent more
      time than those supporting adults did; those supporting adults reported less time
      pressure than those supporting individuals of other ages. Caregiving time's
      effect on depression was not supported, whereas increased time pressure raised
      the risk of depression. CONCLUSIONS: The frequency of depression among parents
      supporting individuals with CP exceeded preceding findings. Time pressure due to
      support appears to directly predict depression. Total time spent caring appears
      unrelated to depression. Implications for Rehabilitation It is necessary to
      prepare various community and family support systems in order to relieve parental
      caregivers' burden and exhaustion. Interventions should focus on parents with
      higher time pressure than parents with high caregiving time. Physical and
      psychological difficulties experienced by parents supporting a child with a
      disability vary with the child's life stage, meaning that families' care burden
      partly depends on the age of the individual with disabilities.

PMID- 29378439
TI  - Steroid-depleted polycystic ovarian syndrome serum promotes in vitro oocyte
      maturation and embryo development.
AB  - In vitro maturation (IVM) of immature oocytes obtained from patients with
      polycystic ovarian syndrome (PCOS) is considered as a novel strategy in order to
      reduce clinical side effects and cost of in vitro fertilization (IVF) technique.
      The aim of this study was to evaluate the effects of PCOS whole and steroid
      depleted serums on in vitro oocyte maturation indices. Patients with PCOS were
      selected according to the Rotterdam criteria. Cumulus-oocyte complexes and blood
      serums were collected and pooled. Cumulus cells and immature oocytes were treated
      with 10% whole or steroid-depleted serums. Stearoyl-CoA desaturase-1 (SCD1) and
      cyclooxygenase-2 (COX2) expression levels in cumulus cells were evaluated by
      quantitative PCR. Fatty acid composition of cumulus cells was analyzed using gas
      liquid chromatography. Polar body observation was considered as the oocyte
      maturation index. Oleate (1.28-fold, p = .006), SCD1 expression (450-fold, p =
      .001), and COX2 expression (35-fold, p = .02) in cumulus cell, as well as oocyte
      maturation (p < .001) and in vitro embryo development (p < .05) were
      significantly higher in treatment with steroid-depleted serum compared to that of
      whole serum. Steroid depletion of PCOS serum improved its capacity to increase
      success rate of oocyte maturation, intra-cytoplasmic sperm injection and early
      embryo development.

PMID- 29378441
TI  - Real-time 3D ultrasound based motion tracking for the treatment of mobile organs
      with MR-guided high-intensity focused ultrasound.
AB  - INTRODUCTION: Magnetic resonance-guided high-intensity focused ultrasound
      (MRgHIFU) treatments of mobile organs require locking the HIFU beam on the
      targeted tissue to maximise heating efficiency. We propose to use a standalone 3
      D ultrasound (US)-based motion correction technique using the HIFU transducer in
      pulse-echo mode. Validation of the method was performed in vitro and in vivo in
      the liver of pig under MR-thermometry. METHODS: 3 D-motion estimation was
      implemented using ultrasonic speckle-tracking between consecutive acquisitions.
      Displacement was estimated along four sub-apertures of the HIFU transducer by
      computing the normalised cross-correlation of backscattered signals followed by a
      triangulation algorithm. The HIFU beam was steered accordingly and energy was
      delivered under real-time MR-thermometry (using the proton resonance frequency
      shift method with online motion compensation and correction of associated
      susceptibility artefacts). An MR-navigator echo was used to assess the quality of
      the US-based motion correction. RESULTS: Displacement estimations from US
      measurements were in good agreement with 1 D MR-navigator echo readings. In
      vitro, the maximum temperature increase was improved by 37% as compared to
      experiments performed without motion correction and temperature distribution
      remained much more focussed. Similar results were reported in vivo, with an
      increase of 35% on the maximum temperature using this US-based HIFU target
      locking. CONCLUSION: This standalone 3D US-based motion correction technique is
      robust and allows maintaining the HIFU focal spot in the presence of motion
      without adding any burden or complexity to MR thermal imaging. In vitro and in
      vivo results showed about 35% improvement in heating efficiency when focus
      position was locked on the target using the proposed technique.

PMID- 29378442
TI  - Female hormonal factors and osteoarthritis of the knee, hip and hand: a narrative
      review.
AB  - Osteoarthritis is a leading cause of disability with no cure. The incidence of
      osteoarthritis is sexually dimorphic: women have a higher rate of osteoarthritis
      than men after the age of 50. Research has investigated the contribution of sex
      hormones, reproductive factors and hormone supplementation to osteoarthritis. It
      has been recognized that different joints are susceptible to different risk
      factors for osteoarthritis. We reviewed the evidence for the effect of endogenous
      sex hormones, reproductive factors and hormone supplementation on joint-specific
      osteoarthritis of the knee, hip and hand. Although the role of these hormonal
      factors in the pathogenesis of osteoarthritis is complex, data suggest that
      endogenous hormones and reproductive factors have a role in the pathogenesis of
      osteoarthritis, especially knee osteoarthritis, with uncertainty for the effect
      of exogenous hormones. From the available data, it is hard to conclude whether
      this is a direct effect of hormonal factors, or whether other factors related to
      these hormonal factors, i.e. obesity and inflammation, have a role in this
      association. Further studies should consider the mediation effect of body weight
      and inflammation, change in body weight throughout life, circulatory levels of
      all endogenous hormones and circulatory levels of hormones after hormone
      supplementation in this complex relationship.

PMID- 29378443
TI  - Thrombolysis in pregnancy: a literature review.
AB  - BACKGROUND: Changes in the coagulation system during pregnancy and puerperium
      produce a physiological hypercoagulable state. These changes are thought to be
      the cause of the higher rates of deep vein thrombosis (DVT), pulmonary embolism
      (PE), stroke, and mechanical prosthetic valve thrombosis (PVT) during pregnancy.
      Thrombolysis can be a treatment option in this case. However, there are no
      available data from randomized controlled trials in pregnant patients and
      information about the security of thrombolytics in pregnancy is missing.
      OBJECTIVE: The aim of this review is to summarize the available data regarding
      the use of thrombolytic agents in pregnancy, describing maternal and fetal
      outcomes. METHODS: A systematic review was performed, searching the electronic
      database MEDLINE for relevant studies published up to April 2017. The search
      included MeSH terms "thrombolytic therapy" OR "fibrinolysis" OR "streptokinase"
      OR "tissue plasminogen activator" AND "pregnancy". All publications that reported
      the use of a thrombolytic agent for DVT, PE, stroke or PVT in pregnancy were
      included in the review. Data on the type and total dose of the thrombolytic
      agent, gestational week, outcome of mothers and children, preterm delivery and
      bleeding complications were described. RESULTS: Sixty-five articles have been
      published describing outcomes in 141 pregnant women with serious thrombotic
      events. There have been no randomized trials involving the use of thrombolytics
      in pregnancy. Only one prospective study was found. Four maternal deaths (2.8%),
      12 major bleeding episodes (8.5%), 13 mild/moderate bleeding episodes (9.2%), two
      fetal death (1.4%), one child death (0.7%), nine miscarriages (6.4%), and 14
      preterm delivery (9.9%) were described. CONCLUSIONS: The risk of using
      thrombolytics in pregnancy seems reasonable taking into account the risk of death
      in a life-threatening event, with the majority of cases presented in this article
      resulting in encouraging outcomes. The complication rate of thrombolytic
      treatment does not seem higher in pregnant women than in the nonpregnant. Poor
      fetal outcome occurred in mothers with poor prognosis. Specific consensus
      recommendations are needed in the use of thrombolytics in pregnancy.

PMID- 29378444
TI  - Further validation of the Chinese (Mandarin) Tinnitus Handicap Inventory:
      comparison between patient-reported and clinician-interviewed outcomes.
AB  - OBJECTIVE: The objective of this study was to evaluate the feasibility of the
      Chinese (Mandarin) Tinnitus Handicap Inventory (THI-C) by comparing patient
      reported and clinician-interviewed outcomes and to raise awareness of the
      difficulties in using adapted international test measures. DESIGN: All patients
      were required to first complete the THI-C independently. Then, clinicians
      conducted a face-to-face interview, explained the exact meaning of each item and
      re-evaluated every item based on the patient's descriptions. During this process,
      patients were encouraged to make comments about each item. Both the self
      administered and clinician-interviewed scores were recorded and compared. STUDY
      SAMPLE: A total of 178 patients who reported tinnitus as a primary complaint were
      included. RESULTS: Among these patients, 88 (49.4%) completed the questionnaire
      independently, while 79 (44.4%) patients experienced difficulty in understanding
      at least one item. The difference between the self-administered and clinician
      interviewed scores was statistically significant (p < 0.01). CONCLUSIONS: The
      feasibility of the THI-C is limited unless a revision is made. Follow-up studies
      are needed for validation when a newly translated self-administered questionnaire
      is put into use. In addition to semantic equivalence and idiomatic equivalence,
      experiential equivalence and conceptual equivalence should also be fully
      considered during the translation process.

PMID- 29378445
TI  - Real-Time Closed-Loop Functional Electrical Stimulation Control of Muscle
      Activation with Evoked Electromyography Feedback for Spinal Cord Injured
      Patients.
AB  - Functional electrical stimulation (FES) is a neuroprosthetic technique to help
      restore motor function of spinal cord-injured (SCI) patients. Through delivery of
      electrical pulses to muscles of motor-impaired subjects, FES is able to
      artificially induce their muscle contractions. Evoked electromyography (eEMG) is
      used to record such FES-induced electrical muscle activity and presents a form of
      [Formula: see text]-wave. In order to monitor electrical muscle activity under
      stimulation and ensure safe stimulation configurations, closed-loop FES control
      with eEMG feedback is needed to be developed for SCI patients who lose their
      voluntary muscle contraction ability. This work proposes a closed-loop FES system
      for real-time control of muscle activation on the triceps surae and tibialis
      muscle groups through online modulating pulse width (PW) of electrical stimulus.
      Subject-specific time-variant muscle responses under FES are explicitly reflected
      by muscle excitation model, which is described by Hammerstein system with its
      input and output being, respectively, PW and eEMG. Model predictive control is
      adopted to compute the PW based on muscle excitation model which can online
      update its parameters. Four muscle activation patterns are provided as desired
      control references to validate the proposed closed-loop FES control paradigm.
      Real-time experimental results on three able-bodied subjects and five SCI
      patients in clinical environment show promising performances of tracking the
      aforementioned reference muscle activation patterns based on the proposed closed
      loop FES control scheme.

PMID- 29378446
TI  - Characterizing EEG Cortical Dynamics and Connectivity with Responses to Single
      Pulse Electrical Stimulation (SPES).
AB  - OBJECTIVES: To model cortical connections in order to characterize their
      oscillatory behavior and role in the generation of spontaneous
      electroencephalogram (EEG). METHODS: We studied averaged responses to single
      pulse electrical stimulation (SPES) from the non-epileptogenic hemisphere of five
      patients assessed with intracranial EEG who became seizure free after
      contralateral temporal lobectomy. Second-order control system equations were
      modified to characterize the systems generating a given response. SPES responses
      were modeled as responses to a unit step input. EEG power spectrum was calculated
      on the 20[Formula: see text]s preceding SPES. RESULTS: 121 channels showed
      responses to 32 stimulation sites. A single system could model the response in
      41.3% and two systems were required in 58.7%. Peaks in the frequency response of
      the models tended to occur within the frequency range of most activity on the
      spontaneous EEG. Discrepancies were noted between activity predicted by models
      and activity recorded in the spontaneous EEG. These discrepancies could be
      explained by the existence of alpha rhythm or interictal epileptiform discharges.
      CONCLUSIONS: Cortical interactions shown by SPES can be described as control
      systems which can predict cortical oscillatory behavior. The method is unique as
      it describes connectivity as well as dynamic interactions.

PMID- 29378447
TI  - Oral administration of l-carnitine improves the clinical outcome of fertility in
      patients with IVF treatment.
AB  - Age-dependent decline of mitochondrial function has been proposed to be a main
      cause of decline of embryo quality. Then, l-carnitine plays important roles in
      reducing the membranous toxicity of free-fatty acids by forming acyl-carnitine
      and promoting beta-oxidation, preventing cell damage. Recent research revealed
      that l-carnitine played important roles in vitro in oocyte growth, oocyte
      maturation and embryo development. However, such beneficial effects of l
      carnitine in vivo have yet to be verified. The effect of oral l-carnitine
      supplementation on embryo quality and implantation potential was examined. A
      total of 214 patients were included in this study. They all previously received
      in vitro fertilization-embryo transfer (IVF-ET) and failed to conceive. Then they
      were administered l-carnitine for 82 days on average and underwent IVF-ET again.
      There were no significant differences in the total number of retrieved oocytes,
      and their maturation and fertilization rates between before and after l-carnitine
      administration. The quality of embryos on Days 3 and 5 after insemination was
      improved following l-carnitine administration (p < .05) in cycles after l
      carnitine administration compared with previous cycles. Healthy neonates were
      born after IVF-ET following l-carnitine administration. Our data suggested that
      oral administration of l-carnitine to fertility patients improved the
      developmental competence of their oocytes after insemination.

PMID- 29378448
TI  - "There are more important things to worry about": attitudes and behaviours
      towards leisure noise and use of hearing protection in young adults.
AB  - OBJECTIVE: Noise-induced hearing problems among young adults are increasing due
      to participation in loud activities. This study explored attitudes towards
      leisure noise, hearing protection, and perceived susceptibility to noise damage
      in young adults with no diagnosed hearing problems. Understanding attitudes and
      behaviours will assist with the future development of strategies to improve
      awareness and use of hearing protection. DESIGN: A qualitative study. STUDY
      SAMPLE: Four focus groups, with 28 adults aged 18-35 years (6 male; 22 female;
      mean age 23 years). RESULTS: Using framework analysis, five themes emerged.
      Earplug use occurred when participants had experienced previous temporary hearing
      damage (i.e. short-lived tinnitus or hearing loss). Others chose not to use
      earplugs because music venues are expected to be loud. Peer behaviours and
      opinions also had a strong influence over earplug use. A lack of knowledge of
      hearing-related damage resulted in a lack of concern for hearing health and other
      health conditions taking priority. CONCLUSIONS: The challenge is to present
      hearing health messages that are relevant and accessible to young adults. Music
      and entertainment venues must also take greater responsibility to protect the
      hearing of its customers by at least informing visitors of the dangers of loud
      music.

PMID- 29378449
TI  - Experience using pipeline embolization device with Shield Technology in a patient
      lacking a full postoperative dual antiplatelet therapy regimen.
AB  - Utilization of flow diverting devices is accompanied with dual antiplatelet
      therapy to reduce the risk of thromboembolic events, even though this increases
      the risk of hemorrhagic complications. The updated Pipeline Flex embolization
      device with Shield Technology has been created using a phosphorylcholine coating
      that reduces thrombogenicity and possibly reduces the need for dual antiplatelet
      therapy. However, because of the potential risk to patients of utilizing a
      pipeline embolization device without dual antiplatelet therapy, the pipeline
      embolization device with Shield Technology has not been tested in human subjects
      without dual antiplatelet therapy, and its contribution to preventing
      thromboembolic events is therefore unknown. We report a case in which a patient,
      following complications that limited his absorption of dual antiplatelet therapy,
      had low levels of dual antiplatelet therapy medications in his bloodstream
      following treatment for an intracranial aneurysm with a pipeline embolization
      device with Shield Technology. The patient recovered without signs of luminal
      stenosis or thromboembolic event.

PMID- 29378450
TI  - Simple aspiration with balloon catheter technique (simple ABC technique) against
      proximal internal carotid artery occlusion in cases of cardiogenic cerebral
      embolism.
AB  - Background In cases of acute ischemic stroke, manual aspiration of the thrombus
      is commonly performed with a balloon guiding catheter placed in the cervical
      segment of the internal carotid artery (ICA). However, most manual aspirations
      using a balloon guiding catheter are combined with inner catheters, as in the
      direct aspiration first pass technique (ADAPT). We experienced some cases of
      acute ischemic stroke with proximal ICA occlusion due to cardiogenic thrombus
      where we obtained sufficient recanalization by simple manual aspiration from
      inflated Optimo 9F balloon catheters (Tokai Medical Products, Japan) placed in
      the origin of the cervical segment of the ICA without any inner catheter or stent
      retriever. We perform by preference this procedure, named the simple Aspiration
      with Balloon Catheter (simple ABC) technique. Herein, we report two recent cases
      and discuss this procedure. Case presentation Case 1: An 80-year-old man with
      paroxysmal atrial fibrillation developed left ICA occlusion. We performed the
      simple ABC technique and obtained a large amount of dark red and white thrombus.
      Puncture-to-reperfusion time was 14 minutes with Thrombolysis in Cerebral
      Infarction (TICI) grade 3. Case 2: A 69-year-old man with chronic atrial
      fibrillation developed left internal carotid occlusion. We performed the simple
      ABC technique and obtained a large amount of dark red thrombus. Puncture-to
      reperfusion time was 15 minutes with TICI grade 2b. Conclusion The simple ABC
      technique is useful to deal with a large amount of thrombus, shortens procedure
      time, enables less invasive thrombectomy, and can shift immediately to subsequent
      procedures such as delivering a stent retriever or ADAPT.

PMID- 29378452
TI  - Remediation of spatial processing disorder (SPD).
AB  - OBJECTIVE: To determine the efficacy of deficit-specific remediation for spatial
      processing disorder, quantify effects of remediation on functional listening, and
      determine if remediation is maintained. DESIGN: Participants had SPD, diagnosed
      using the Listening in Spatialised Noise-Sentences test. The LiSN and Learn
      software was provided as auditory training. Post-training, repeat LiSN-S testing
      was conducted. Questionnaires pre- and post-training acted as subjective measures
      of remediation. A late-outcome assessment established long-term effects of
      remediation. STUDY SAMPLE: Sixteen children aged between 6;3 [years; months] and
      10;0 completed between 20 and 146 training games. RESULTS: Post-training LiSN-S
      improved in measures containing spatial cues (p <= 0.001) by 2.0 SDs (3.6 dB) for
      DV90, 1.8 SDs for SV90 (3.2 dB), 1.4 SDs for spatial advantage (2.9 dB) and 1.6
      SDs for total advantage (3.3 dB). Improvement was also found in the DV0 condition
      (1.4 dB or 0.5 SDs). Post-training changes were not significant in the talker
      advantage measure (1.0 dB or 0.4 SDs) or the SV0 condition (0.3 dB or 0.1 SDs).
      The late-outcome assessment demonstrated improvement was maintained. Subjective
      improvement post-remediation was observed using the parent questionnaire.
      CONCLUSIONS: Children with SPD had improved ability to utilise spatial cues
      following deficit-specific remediation, with the parent questionnaire sensitive
      to remediation. Effects of the remediation also appear to be sustained.

PMID- 29378453
TI  - 5-Fluorouracil ethosomes - skin deposition and melanoma permeation synergism with
      microwave.
AB  - This study focuses on the use of ethosome and microwave technologies to
      facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in
      vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion
      technique and had their size, zeta potential, morphology, drug content and
      encapsulation efficiency characterized. The skin was pre-treated with microwave
      at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in
      vitro and in vivo skin drug permeation as well as retention evaluation. The drug
      and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28
      melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted
      significant drug deposition in skin from ethosomes in vitro while keeping the
      level of drug permeation unaffected. Similar observations were obtained in vivo
      with reduced drug permeation into blood. Combination ethosome and microwave
      technologies enhanced intracellular localization of ethosomes through
      fluidization of cell membrane lipidic components as well as facilitating
      endocytosis by means of clathrin, macropinocytosis and in particularly lipid
      rafts pathways. The synergistic use of microwave and ethosomes opens a new
      horizon for skin malignant melanoma treatment.

PMID- 29378451
TI  - Hydrogen sulfide increases glutathione biosynthesis, and glucose uptake and
      utilisation in C2C12 mouse myotubes.
AB  - Diabetic patients have lower blood concentrations of hydrogen sulfide (H2S), L
      cysteine (LC), and glutathione (GSH). Using C2C12 mouse myotubes as a model, this
      study investigates the hypothesis that the beneficial effects of LC
      supplementation are mediated by upregulation of the H2S status under diabetic
      conditions. Results show that exogenous administration of sodium hydrosulfide
      (NaHS, 10 or 20 uM; 6 hours), a H2S donor, significantly (p < .05) upregulates
      the gene expression of cystathionine-gamma-lyase (CSE), LC transporter
      (Slc7a11/xCT), and the genes involved in GSH biosynthesis. Additionally, it
      reduces homocysteine (HCys), reactive oxygen species (ROS) production, and
      enhances cellular LC, H2S, and glucose uptake and utilisation in myoblasts. The
      use of CSE siRNA to induce deficient endogenous H2S production causes an increase
      in H2O2, ROS, HCys levels, and downregulation of GSH biosynthesis pathway
      enzymes. In additional, CSE knockdown downregulates glucose transporter type 4
      (GLUT4) and gene expression of its key transcription factors, and reduces glucose
      uptake in C2C12 myotubes. CSE knockdown cells showed specific increases in the
      protein S-glutathionylation of LC transporter and GLUT4 along with increased
      total protein S-glutathionylation. Taken together, evidence from this study
      provides molecular insights into the importance of the CSE/H2S system in
      maintaining the cellular glutathione and glucose homeostasis in C2C12 myotubes.

PMID- 29378454
TI  - Possible role of DPP4 inhibitors to promote hippocampal neurogenesis in
      Alzheimer's disease.
AB  - As well-known to the scientific community, Alzheimer's disease (AD) is an
      irreversible neurodegenerative disease that ends up with impairment of memory and
      cognition. Patient quality of life can be enhanced by targeting neurogenesis as a
      therapeutic paradigm. Preserving functional activity of SDF-1alpha and GLP-1 by
      DPPIV inhibition will enhance the homing of stem cells and modulate cell
      signalling pathways. The non-invasive approach presented in this article is a
      major advantage for managing AD, as regular/conventional stem-cell therapy
      necessarily relies on the application of regenerative stem cells exogenously.
      Using DPP-4 inhibitors to achieve the SDF-1alpha/CXCR4 axis stabilisation and
      augmenting GLP-1 levels, will enhance the homing/recruitment of brain resident
      and non-resident circulating stem cells/progenitor cells towards the sites of
      lesion to increase synaptic plasticity, a promising approach and also a novel one
      as well.

PMID- 29378455
TI  - Twelve tips for medical students to establish a collaborative flashcard project.
AB  - Medical students employ various study strategies to master large amounts of
      information during their medical education. Digital flashcards are an
      interactive, self-directed study stool that may improve knowledge retention by
      combining the principles of active recall and spaced-repetition. They may be
      studied during and beyond undergraduate medical education. However, making
      flashcards can be an onerous task. In this article, we describe twelve tips on
      how to establish and maintain a collaborative digital flashcard project based on
      the undergraduate medical curriculum.

PMID- 29378457
TI  - Review of long-term outcomes of disc arthroplasty for symptomatic single level
      cervical degenerative disc disease.
AB  - INTRODUCTION: Cervical disc arthroplasty (CDA) was developed as an alternative
      for anterior cervical discectomy and fusion (ACDF) for nerve root decompression.
      The rationale behind CDA was to help prevent adjacent segment degeneration which
      potentially may lead to additional surgery. Multiple randomized controlled trials
      have evaluated a myriad of disc arthroplasty devices over the past 10 years and
      provided data regarding clinical benefits and safety. Their long-term data,
      reporting results at 5-10 years, presents the opportunity to comment on the
      overall efficacy, safety and reported complications of these devices. This report
      reviews results of the Prestige, proDisc-C, Mobi-C Disc and various other
      arthroplasty devices and provides an overall report of the longest term available
      data and comparisons between devices. Areas covered: This review summarizes
      previously published articles in a literature search using keywords: 'cervical
      disc arthroplasty', 'cervical total disc replacement', 'anterior cervical
      decompression and fusion', 'anterior cervical arthrodesis', 'symptomatic
      degenerative disc disease' and commercial names of devices. Expert commentary:
      CDA, with the devices reviewed, resulted in favorable outcomes in comparison to
      ACDF for the treatment of symptomatic cervical degenerative disc disease (DDD)
      taking in to account the long-term functional recovery, adverse events,
      development of adjacent segment degeneration and subsequent surgical
      interventions.

PMID- 29378458
TI  - Hyperbaric Oxygen therapy effects on bone regeneration in Type 1 diabetes
      mellitus in rats.
AB  - PURPOSE: The aim of this study was evaluate the effect of HBO on diabetic rats.
      MATERIALS AND METHODS: Twenty rats were distributed into four groups (n = 5):
      Control (C); Control + HBO (CH); Diabetes (D) and Diabetes + HBO (DH). Diabetes
      was induced by streptozotocin, and bone defects were created in both femurs in
      all animals. HBO therapy began immediately after surgery and was performed daily
      in the CH and DH groups. After 7 days, the animals were euthanized. The femurs
      were removed, demineralized, embedded in paraffin, and histologic images were
      analyzed. RESULTS: Qualitative histologic analyses showed more advanced stage
      bone regeneration in control groups (C and CH) compared with diabetic groups (D
      and DH). Histomorphometric analysis showed significantly increased bone
      neoformation in CH compared with the other groups (p < 0.001). Diabetic Group (D)
      showed decreased bone neoformation compared with non-diabetic groups (C and CH)
      (p < 0.001); however DH did not differ from C Group (p > 0.05). The mast cell
      population increased in CH compared with the other groups (C, D, and DH) (p <
      0.05). The mast cell population did not differ between D and DH Groups.
      CONCLUSIONS: This study showed that HBO therapy improved early bone regeneration
      in diabetic rats and increased the mast cell population only in non-diabetic
      animals. HBO was shown to be important treatment for minimizing deleterious
      effects of diabetes on bone regeneration.

PMID- 29378459
TI  - Auditory brainstem, middle and late latency responses to short gaps in noise at
      different presentation rates.
AB  - OBJECTIVE: The effects of rate on auditory-evoked potentials (AEP) to short noise
      gaps (12 ms) recorded at high sampling rates using wide-band filters were
      investigated. DESIGN: Auditory brainstem (ABR), middle latency (MLR), late
      latency (LLR) and steady-state (ASSR) responses were simultaneously recorded in
      adult subjects at four gap rates (0.5, 1, 5 and 40 Hz). Major components (V, Na,
      Pa, Nb, Pb, N1 and P2) were identified at each rate and analysed for
      latency/amplitude characteristics. Gap responses at 40 Hz were recovered from
      Quasi-ASSRs (QASSR) using the CLAD deconvolution method. STUDY SAMPLE: Fourteen
      right ears of young normal hearing subjects were tested. RESULTS: All major
      components were present in all subjects at 1 Hz. P1 (P50) appeared as a low-pass
      filtered component of Pa and Pb waves. At higher rates, N1 and P2 disappeared
      completely while major ABR-MLR components were identified. Peak latencies were
      mostly determined by noise onsets slightly delayed by offset responses.
      CONCLUSIONS: Major AEP components can be recorded to short gaps at 1 Hz using
      high sampling rates and wide-band filters. At higher rates, only ABR and MLRs can
      be recorded. Such simultaneous recordings may provide a complete assessment of
      temporal resolution and processing at different levels of auditory pathways.

PMID- 29378456
TI  - Developments in drug delivery of bioactive alkaloids derived from traditional
      Chinese medicine.
AB  - The bioactive alkaloids (e.g. vincristine, hydroxycamptothecin, ligustrazine, and
      so on) from traditional Chinese medicine (TCM) have exerted potent efficacies
      (e.g. anti-tumor, anti-inflammation, immunosuppression, etc.). However, a series
      of undesirable physicochemical properties (like low solubility and weak
      stability) and baneful pharmacokinetic (PK) profiles (e.g. low bioavailability,
      short half time, rapid clearance, etc.) have severely restricted their
      applications in clinic. In addition, some side effects (like cumulative
      toxicities caused by high-frequency administration and their own toxicities) have
      recently been reported and also confined their clinical uses. Therefore,
      developments in drug delivery of such alkaloids are of significance in improving
      their drug-like properties and, thus, treatment efficiencies in clinic.
      Strategies, including (i) specific delivery via liposomes; (ii) sustained
      delivery via nanoparticles, gels, and emulsions; and (iii) transdermal delivery
      via ethosomes, solid lipid nanoparticles, and penetrating enhancers, have been
      reported to improve the pharmacokinetic and physicochemical characters of
      problematic TCM alkaloids, decline their adverse effects, and thus, boost their
      curative efficacies. In this review, the recent reports in this field were
      comprehensively summarized with the aim of providing an informative reference for
      relevant readers.

PMID- 29378460
TI  - The modifying effect of positive emotion on the relationship between cognitive
      impairment and disability among older Mexican Americans: a cohort study.
AB  - OBJECTIVE: To determine if positive emotion modifies the relationship between
      cognitive impairment and activities of daily living disability status over 10
      years in Mexican American adults aged 75 years and older. METHODS: A
      retrospective cohort design using data from the Hispanic established populations
      for the epidemiologic studies of the elderly. About 2674 participants aged 75
      years and older were included and followed over 10 years. Cognition was measured
      using the mini-mental state examination, positive emotion was measured using four
      questions from the Center for Epidemiologic Studies Depression Scale, and
      disability was measured using seven activities of daily living items. A series of
      generalized estimating equations models were used, with the initial analysis
      including those with disability at baseline and subsequent analyses excluding
      disability at baseline. RESULTS: Positive emotion and cognitive impairment
      consistently decreased and increased risk for activities of daily living
      disability, respectively. Positive emotion was a significant modifier in the
      cross-sectional analysis, and was not a statistically significant modifier in the
      longitudinal or predictive series analysis. CONCLUSIONS: Positive emotion and
      cognitive impairment differentially affect the risk of developing activities of
      daily living disability. Further research is needed to explore the interaction of
      positive emotion and cognitive impairment, and to identify appropriate
      interventions that address the specific cognitive and emotional needs of older
      Mexican Americans. Implications for rehabilitation Promoting emotional well-being
      may be protective against incident disability for older adults. Cognitive
      impairment significantly predicts incident disability in activities of daily
      living and should be considered an early indicator of impending disability for
      older adults.

PMID- 29378461
TI  - Bringing the patient back in: behavioral decision-making and choice in medical
      economics.
AB  - We explore the behavioral methodology and "revolution" in economics through the
      lens of medical economics. We address two questions: (1) Are mainstream economic
      assumptions of utility-maximization realistic approximations of people's actual
      behavior? (2) Do people maximize subjective expected utility, particularly in
      choosing from among the available options? In doing so, we illustrate-in terms of
      a hypothetical experimental sample of patients with dry eye diagnosis-why and how
      utility in pharmacoeconomic assessments might be valued differently by patients
      when subjective psychological, social, cognitive, and emotional factors are
      considered. While experimentally-observed or surveyed behavior yields stated
      (rather than revealed) preferences, behaviorism offers a robust toolset in
      understanding drug, medical device, and treatment-related decisions compared to
      the optimizing calculus assumed by mainstream economists. It might also do so
      more perilously than economists have previously understood, in light of the
      intractable uncertainties, information asymmetries, insulated third-party agents,
      entry barriers, and externalities that characterize healthcare. Behavioral work
      has been carried out in many sub-fields of economics. Only recently has it been
      extended to healthcare. This offers medical economists both the challenge and
      opportunity of balancing efficiency presumptions with relatively autonomous
      patient choices, notwithstanding their predictable, yet seemingly consistent,
      irrationality. Despite its comparative youth and limitations, the scientific
      contributions of behaviorism are secure and its future in medical economics
      appears to be promising.

PMID- 29378462
TI  - Comparison between microwave ablation and lobectomy for stage I non-small cell
      lung cancer: a propensity score analysis.
AB  - PURPOSE: To compare the effectiveness and complication between microwave ablation
      and lobectomy for stage I non-small cell lung cancer. MATERIALS AND METHODS: This
      retrospective study was approved by two institutional ethics committees and all
      patients were provided with informed consent. From January 2000 to December 2010,
      54 and 795 stage I patients who underwent microwave ablation and lobectomy were
      included in this study. A matched cohort composed of 54 and 108 patients in the
      microwave ablation and the lobectomy group were selected after adjustment with
      1:2 propensity score matching. The overall survival and disease-free survival
      were evaluated. Survival curves were constructed with the Kaplan-Meier method and
      compared by using the log-rank test. RESULTS: The 1, 3 and 5-year Overall survive
      were 100, 92.6 and 50.0% for MWA group and 100, 90.7 and 46.3% for lobectomy
      group. The 1, 3 and 5-year disease free survival was 98.1, 79.6 and 37.0% for MWA
      group and 98.1, 81.5 and 29.6% for lobectomy group. There was no significant
      difference between two groups in overall survival (p = 0.608) and disease free
      survival (p = 0.672). Additionally, local or distant metastasis rate (p = 0.544)
      were not significantly different between two groups while the complication rate
      in the MWA group was significantly lower than the lobectomy group (p = 0.008).
      CONCLUSION: Microwave ablation has similar therapeutic effect compared with
      lobectomy for stage I non-small cell lung cancer, but with fewer complication and
      less pain.

PMID- 29378463
TI  - Development and anti-Candida evaluation of the vaginal delivery system of
      amphotericin B nanosuspension-loaded thermogel.
AB  - Vulvovaginal candidiasis (VVC) is a typical kind of vaginal mucosal infection.
      Herein, we developed a novel vaginal delivery system of amphotericin B (AmB)
      nanosuspension-loaded thermogel (AmB NPs/thermogel) utilising pharmaceutical
      technique of high-pressure homogenisation and Poloxamer P407/P188 hydrogel. The
      stabiliser and hydrogel materials of the formulation were tested to maintain
      proper sol-gel transition as well as the relative stability of the particle size
      of AmB nanosuspension in the thermogel. The particle size of AmB nanosuspensions
      in the hydrogel was ~247 nm. Transmission electron microscopy images confirmed
      the round-shape morphology of AmB nanoparticles in AmB NPs/thermogel, while that
      of irregular morphology of merely AmB nanosuspensions without stabiliser and
      hydrogel materials. AmB could be sustained release for ~12 h in vitro. In vivo
      drug content in the vaginal tissue was also evaluated with 87, 47, 33 and 6.7%
      drug remaining after 1, 3, 6 and 12 h, respectively. The in vivo anti-Candida
      test was conducted on candidiasis-infected mice model. In the same drug dose of
      2.5 mg/kg, AmB NPs/thermogel showed better anti-Candida efficiency compared with
      commercial AmB effervescent tablet. This delivery system might show some insights
      for the vaginal formulation development of other hydrophobic antifungal drugs.

PMID- 29378464
TI  - Preface to DMR special edition 'Cannabinoid receptors and ligands: therapeutic
      drug development and abuse potential'.

PMID- 29378465
TI  - Development a hyaluronic acid ion-pairing liposomal nanoparticle for enhancing
      anti-glioma efficacy by modulating glioma microenvironment.
AB  - Glioma, one of the most common brain tumors, remains a challenge worldwide. Due
      to the specific biological barriers such as blood-brain barrier (BBB), cancer
      stem cells (CSCs), tumor associated macrophages (TAMs), and vasculogenic mimicry
      channels (VMs), a novel versatile targeting delivery for anti-glioma is in urgent
      need. Here, we designed a hyaluronic acid (HA) ion-pairing nanoparticle. Then,
      these nanoparticles were encapsulated in liposomes, termed as DOX-HA-LPs, which
      showed near-spherical morphology with an average size of 155.8 nm and uniform
      distribution (PDI = 0.155). HA was proven to specifically bind to CD44 receptor,
      which is over-expressed on the surface of tumor cells, other associated cells
      (such as CSCs and TAMs) and VMs. We systematically investigated anti-glioma
      efficacy and mechanisms in vivo and in vitro. The strong anti-glioma efficacy
      could attribute to the accumulation in glioma site and the regulation of tumor
      microenvironment with depletion of TAMs, inhibition of VMs, and elimination of
      CSCs.

PMID- 29378467
TI  - Microencapsulation of Bifidobacterium bifidum BB01 by xanthan-chitosan:
      preparation and its stability in pure milk.
AB  - Xanthan-chitosan (XC) and xanthan-chitosan-xanthan (XCX) were employed for
      microencapsulation of Bifidobacterium bifidum BB01 using extrusion technique. To
      optimize the process of B. bifidum BB01 microcapsules based on XC hydrogels,
      response surface methodology was employed to obtain the best possible combination
      of chitosan concentration, xanthan-B. bifidum BB01 mixture (XBM)/chitosan,
      stirring time for the maximum viable count and encapsulation yield. The optimum
      conditions were: chitosan concentration of 0.84 g.mL-1, XBM/chitosan of 1:9.0,
      stirring time of 60 min with high viable count and encapsulation yield of 1.52 +/
      0.15 * 1010 CFU.g-1, 90 +/- 0.65%, respectively. In addition, the effective
      encapsulation system (XC and XCX) resulted in improvement in survival of B.
      bifidum BB01 compared to non-encapsulated cells during 3 weeks storage at 4 and
      25  degrees C in pure milk.

PMID- 29378468
TI  - The self-reference effect in memory: an implicit way to assess affective self
      representations in social anxiety.
AB  - This study was designed to assess, through the self-reference effect in memory,
      whether affective self-representations were modulated by the retrieval conditions
      and the severity of social anxiety. Three groups (high socially anxious, low
      socially anxious and non-anxious) were compared on a self-referential task that
      involved encoding affective trait adjectives under three conditions: self
      reference encoding, encoding with reference to the perception of self by others,
      and other-reference encoding. Memory for trait adjectives was tested on both a
      free recall task and a Remember/Know/Guess recognition task. The results revealed
      that while socially anxious individuals explicitly rated as self-descriptive and
      recalled more positive than negative trait adjectives like non-anxious
      participants, this positivity bias was respectively reduced and erased among low
      and high socially anxious participants when recollecting the same adjectives
      encoded in reference to the self. These findings are discussed in relation to
      their contribution to the understanding of the emotional memory biases related to
      the retrieval of self-knowledge in social anxiety. In particular, they highlight
      the necessity of using the self-reference effect in memory rather than mere self
      endorsement of trait adjectives when assessing the efficacy of cognitive
      therapies for social anxiety.

PMID- 29378466
TI  - Intra-individual variation of miRNA expression levels in human plasma samples.
AB  - BACKGROUND: Circulating miRNAs as potential non-invasive biomarkers for disease
      risk assessment and cancer early diagnosis have attracted increasing interest.
      Little information, however, is available regarding the intra-individual
      variation of circulating miRNA levels. METHODS: We measured expression levels of
      a panel of 800 miRNAs in repeated plasma samples from 51 healthy individuals that
      were collected 6 to 12 months apart and evaluated the intra-individual variation
      by the intra-class correlation coefficient (ICC). RESULTS: After background
      correction, a total of 185 miRNAs were detected in at least 10% of the plasma
      samples, with 69 and 28 miRNAs being detected in 50% and 90% of samples,
      respectively. The median ICC was 0.46 for these 185 miRNAs. Among them, 41% (75
      miRNAs) had an ICC >= 0.5, and 23% (42 miRNAs) had an ICC >= 0.6. The ICC is
      higher for miRNAs with higher expression levels or higher detection rates, when
      compared to those with lower expression levels or lower detection rates.
      CONCLUSIONS: These results suggest that common circulating miRNAs are stable over
      a relatively long period and can serve as reliable biomarkers for epidemiological
      and clinical research.

PMID- 29378471
TI  - Nanaomycin A Treatment Promotes Hepatoblast Differentiation from Human iPS Cells.
AB  - Human induced pluripotent stem cell-derived hepatocyte-like cells (HLCs) are
      expected to be utilized in pharmaceutical research, including drug screening.
      However, the hepatocyte functions of the HLCs are still lower than those of human
      hepatocytes. Therefore, we attempted to improve the hepatocyte differentiation
      method by modulating the DNA epigenetic status. We first examined the expression
      profiles of the maintenance DNA methyltransferase (DNMT) 1 and the de novo DNMTs
      DNMT3A and DNMT3B, all of which are essential for mammalian development. Among
      these DNMTs, the expression levels of DNMT3B were significantly decreased during
      the hepatoblast differentiation. To accelerate the hepatoblast differentiation, a
      DNMT3B-selective inhibitor, nanaomycin A, was treated during the hepatoblast
      differentiation. The gene expression levels of hepatoblast markers (such as alpha
      fetoprotein and hepatocyte nuclear factor 4 alpha) were increased by the
      nanaomycin A treatment. On the other hand, the gene expression levels of
      hepatoblast markers were decreased by DNMT3B overexpression. These results
      suggest that it might be possible to promote the hepatoblast differentiation by
      DNMT3B inhibition using nanaomycin A. Importantly, we also confirmed that the
      hepatocyte differentiation potency of nanaomycin A-treated hepatoblast-like cells
      was higher than that of dimethyl sulfoxide-treated hepatoblast-like cells. Our
      findings should assist in the future generation of functional HLCs for
      pharmaceutical research.

PMID- 29378472
TI  - Discriminatory miRNAs for the Management of Papillary Thyroid Carcinoma and
      Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) variants have several overlapping
      clinical and pathological features. The World Health Organization recently
      published a new classification of thyroid tumors containing significant
      revisions. Encapsulated papillary thyroid carcinoma (EPTC) has been recognized as
      a distinctive variant of PTC. The noninvasive encapsulated follicular variant of
      PTC has been reclassified as noninvasive follicular thyroid neoplasms with
      papillary-like nuclear features (NIFTP). Different neoplasms are associated with
      different outcomes and require different clinical management. The objective of
      this study was to explore the miRNA expression patterns specific for classic PTC
      (cPTC), EPTC, follicular variant of PTC, and NIFTP in order to identify
      biomarkers of diagnostic and prognostic utility aiming for better clinical
      decisions. METHODS: The expression of 84 miRNAs was determined by quantitative
      real-time polymerase chain reaction in 113 thyroid tissues of PTC (classic,
      encapsulated, and follicular), NIFTP, and hyperplasia lesions. Expression of the
      same miRNAs was tested in pre- and postoperative whole-blood samples. RESULTS:
      Several miRNAs were differentially expressed in the different groups. Expression
      profile of miRNAs in the tissue was similarly reflected in the circulation.
      Receiver operating characteristic curve analysis showed that miR-7-5p, miR-222
      3p, and miR-146b-5p can discriminate between the different groups with high
      sensitivity and specificity. Downregulation of miR-144-3p, miR-15a-5p, miR-20a
      5p, miR-32-5p miR-142-5p, miR-143-3p, and miR-20b-5p is associated with
      aggressive behavior in cPTC. Circulating miR-146b-5p, miR-222-3p, miR-155-5p, and
      miR-378a-3p are potential diagnostic and follow up biomarkers for PTC.
      CONCLUSION: Downregulation of miR-7-5p discriminates NIFTP from hyperplasia.
      Upregulation of miR-222-3p discriminates follicular variant of PTC from NIFTP.
      High levels of miR-146b-5p distinctively characterize cPTC. These miRNAs are
      useful biomarkers in the diagnosis of PTC and NIFTP, and help to avoid
      unnecessary thyroidectomy and improve clinical management.

PMID- 29378470
TI  - Prunella vulgaris L. Exerts a Protective Effect Against Extrinsic Aging Through
      NF-kappaB, MAPKs, AP-1, and TGF-beta/Smad Signaling Pathways in UVB-Aged Normal
      Human Dermal Fibroblasts.
AB  - Prunella vulgaris L., a well-known traditional Chinese herbal medicine, has anti
      inflammatory and antioxidant activities. In the present study, the underlying
      molecular mechanisms of the protective effect of P. vulgaris extract (PVE) were
      investigated in UVB-irradiated normal human dermal fibroblasts (NHDFs). The mRNA
      expression of matrix metalloproteinases (MMPs), procollagen type I, and
      cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha),
      was determined by reverse transcription-polymerase chain reaction. The expression
      of anti-photoaging-related signaling molecules in the NF-kappaB, MAPK/AP-1, and
      TGF/Smad pathways was assessed by western blot. We observed that PVE blocked the
      upregulated production of radical oxygen species induced in UVB-irradiated NHDFs
      in a dose-dependent manner. Treatment with PVE also significantly ameliorated the
      mRNA levels of MMPs, procollagen type I, TNF-alpha, and IL-6. In addition, the
      phosphorylation level of c-Jun and c-Fos was decreased through the attenuated
      expression levels of p-ERK and p-JNK after treatment with PVE. Furthermore, cells
      treated with PVE showed inhibited Smad 7 and increased Smad 2/3 expression in the
      TGF-beta/Smad signaling pathway. Hence, synthesis of procollagen type I, a
      precursor of collagen I, was promoted. These findings indicate that treatment
      with PVE has a potential protective effect against UVB-induced photoaging and
      photoinflammation.

PMID- 29378473
TI  - Alpha suppression over parietal electrode sites predicts decisions to trust.
AB  - Decisions to trust help form the basis of relationships and society yet little is
      known about their neurophysiology. We told participants they were playing a coin
      toss game with a trustworthy and an untrustworthy person and measured their
      neural activity with EEG as they decided whether to trust those fictitious
      interaction partners. Target people ostensibly correctly reported the outcome of
      a coin toss on 66% of trials. Behaviorally, participants probability matched and
      chose to trust the reported coin flips from each profile equally by the end of
      100 trials. Electrophysiologically, there were reliable differences in the
      pattern of oscillatory activity in the alpha band (8-13Hz) over parietal
      electrode sites 1-3 s prior to their trust decisions. Specifically, for
      trustworthy profiles, there was greater alpha suppression for trust decisions vs.
      distrust decisions. Conversely, for untrustworthy profiles there was greater
      alpha suppression for distrust decisions vs. trust decisions. This differential
      activity (trust minus distrust) also predicted the number of trust decisions
      made. Our results indicate that the intentions to trust people form very early in
      the processing stream and manifest as alpha suppression over parietal cortex.

PMID- 29378475
TI  - Commentary on Some Recent Theses Relevant to Combating Aging: February 2018.

PMID- 29378474
TI  - Circulating BRAFV600E Levels Correlate with Treatment in Patients with Thyroid
      Carcinoma.
AB  - BACKGROUND: BRAFV600E is the most common mutation in papillary thyroid carcinoma
      (PTC) and can be associated with aggressive disease. Previously, a highly
      sensitive blood RNA-based BRAFV600E assay was reported. The objective of this
      study was to assess the correlation of BRAFV600E circulating tumor RNA levels
      with surgical and medical treatment. METHODS: Circulating BRAFV600E levels were
      assessed in (i) a murine model of undifferentiated (anaplastic) thyroid carcinoma
      with known BRAFV600E mutation undergoing BRAFV600E-inhibitor (BRAFi) treatment,
      and (ii) in 111 patients enrolled prior to thyroidectomy (n = 86) or treatment of
      advanced recurrent or metastatic PTC (n = 25). Blood samples were drawn for
      BRAFV600E analysis before and after treatment. Testing characteristics were
      assessed and positivity criteria optimized. Changes in blood BRAFV600E values
      were assessed and compared to clinical characteristics and response to therapy.
      RESULTS: In a murine model of anaplastic thyroid carcinoma with BRAFV600E
      mutation, blood BRAFV600E RNA correlated with tumor volume in animals treated
      with BRAFi. In tissue BRAFV600E-positive (n = 36) patients undergoing initial
      surgery for PTC, blood BRAFV600E levels declined postoperatively (median 370.0
      178.5 fg/ng; p = 0.002). In four patients with metastatic or poorly
      differentiated thyroid carcinoma receiving targeted therapies, blood BRAFV600E
      declined following therapy and corresponded with radiographic evidence of partial
      response or stable disease. CONCLUSIONS: This study shows the correlation of
      blood BRAFV600E levels in response to treatment in both an established animal
      model of thyroid cancer and in patients with BRAFV600E-positive tumors with all
      stages of disease. This assay represents an alternative biomarker in patients
      with positive thyroglobulin antibodies, and tumors, which do not express
      thyroglobulin.

PMID- 29378476
TI  - Health-related quality of life and cost-effectiveness analysis of gum chewing in
      patients undergoing colorectal surgery: results of a randomized controlled trial.
AB  - BACKGROUND: Postoperative ileus (POI) and anastomotic leakage (AL) following
      colorectal surgery severely increase healthcare costs and decrease quality of
      life. This study evaluates the effects of reducing POI and AL via perioperative
      gum chewing compared to placebo (control) on in-hospital costs, health-related
      quality of life (HRQoL), and assesses cost-effectiveness. METHODS: In patients
      undergoing elective, open colorectal surgery, changes in HRQoL were assessed
      using EORTC-QLQ-C30 questionnaires and costs were estimated from a hospital
      perspective. Incremental cost-effectiveness ratios were estimated. RESULTS: In
      112 patients, mean costs for ward stay were significantly lower in the gum
      chewing group when compared to control (?3522 (95% CI ?3034-?4010) versus ?4893
      (95% CI ?3843-?5942), respectively, p = .020). No differences were observed in
      mean overall in-hospital costs, or in mean change in any of the HRQoL scores or
      utilities. Gum chewing was dominant (less costly and more effective) compared to
      the control in more than 50% of the simulations for both POI and AL. CONCLUSION:
      Reducing POI and AL via gum chewing reduced costs for ward stay, but did not
      affect overall in-hospital costs, HRQoL, or mapped utilities. More studies with
      adequate sample sizes using validated questionnaires at standardized time points
      are needed.

PMID- 29378478
TI  - Perspectives of Decision-Making for Corneal Donation: A Qualitative Research
      Among Cancer Patients.
AB  - This study investigates the subjective experiences of terminal cancer patients
      who expedite their corneal donation decisions. The percentage of cancer patients
      who donate their corneas postmortem is low in Taiwan. The reasons are complex and
      needs further exploration. A qualitative design using content analysis was used.
      A semistructured interview approach was adopted to interview cancer patients
      recruited from a cancer ward in northern Taiwan. The study findings show that the
      factors contributing to an aversive preference of cancer patients included the
      necessity to consider the emotions of family members, traditional perceptions,
      religious reasons, disease, and no reason at all. Most cancer patients maintain a
      negative stance toward corneal donation. The results obtained in the present
      study can be used as a reference for future in-service education and promotional
      efforts regarding corneal donation. Discussing cornea donation needs to become a
      routine end-of-life care discussion.

PMID- 29378477
TI  - A review of the in vitro and in vivo valved holding chamber (VHC) literature with
      a focus on the AeroChamber Plus Flow-Vu Anti-static VHC.
AB  - Valved holding chambers (VHCs) reduce the need for inhalation-actuation
      coordination with pressurized metered dose inhalers (pMDIs), reduce oropharyngeal
      drug deposition and may improve lung deposition and clinical outcomes compared to
      pMDIs used alone. While VHCs are thus widely advocated for use in vulnerable
      patient groups within clinical and regulatory guidelines, there is less consensus
      as to whether the performance differences between different VHCs have clinical
      implications. This review evaluates the VHC literature, in particular the data
      pertaining to large- versus small-volume chambers, aerosol performance with a VHC
      adjunct versus a pMDI alone, charge dissipative/conducting versus non-conducting
      VHCs, and facemasks, to ascertain whether potentially meaningful differences
      between VHCs exist. Inconsistencies in the literature are examined and explained,
      and relationships between in vitro and in vivo data are discussed. A particular
      focus of this review is the AeroChamber Plus(r) Flow-Vu(r) Anti-static VHC, the
      most recent iteration of the AeroChamber VHC family.

PMID- 29378479
TI  - Preimplantation Genetic Diagnosis of Multiple Endocrine Neoplasia Type 2A Using
      Informative Markers Identified by Targeted Sequencing.
AB  - BACKGROUND: The revised guidelines for the management of medullary thyroid
      carcinoma recommend that genetic counseling regarding reproductive options,
      including preimplantation genetic diagnosis (PGD), be considered for all RET
      mutation carriers of reproductive age to avoid the transmission of multiple
      endocrine neoplasia type 2 (MEN2). However, the high complexity and cost of PGD
      have hindered its widespread use. Thus, it is necessary to establish a simple and
      relatively inexpensive method to facilitate the PGD of MEN2. PATIENTS AND
      METHODS: A customized Nimblegen EZ sequence capture array was designed to capture
      the targeted regions, including the RET gene, and 1 Mb range on each side of the
      RET gene. Targeted, capture-based next-generation sequencing of three members of
      one family with MEN2A (the couple and the paternal father) was conducted to
      identify the informative markers. The diagnosis of the embryos was achieved
      through haplotype analysis based on informative markers and causative mutation.
      RESULTS: Based on the sequencing results, 173 informative markers were detected,
      which were sufficient for the subsequent use for PGD. Seven informative markers
      and the causative mutation (RETC634Y) were selected and subjected to Sanger
      sequencing. Through haplotype analysis, four embryos without inheritance of the
      mutation haplotype of the RET gene were diagnosed as unaffected. One unaffected
      embryo was transferred, with one healthy baby born at 38 gestational weeks.
      CONCLUSIONS: Targeted, capture-based next-generation sequencing for
      identification of informative markers together with Sanger sequencing is an easy
      and efficient method for the PGD of monogenic diseases such as MEN2.

PMID- 29378481
TI  - Meta-analysis of the effects of cognitive-behavioral therapy on the core eating
      disorder maintaining mechanisms: implications for mechanisms of therapeutic
      change.
AB  - The original and enhanced cognitive model of eating disorders proposes that
      cognitive-behavioral therapy (CBT) "works" through modifying dietary restraint
      and dysfunctional attitudes towards shape and weight. However, evidence
      supporting the validity of this model is limited. This meta-analysis examined
      whether CBT can effectively modify these proposed maintaining mechanisms.
      Randomized controlled trials that compared CBT to control conditions or non-CBT
      interventions, and reported dietary restraint and shape and weight concern
      outcomes were searched. Twenty-nine trials were included. CBT was superior to
      control conditions in reducing shape (g=0.53) and weight (g=0.63) concerns, and
      dietary restraint (g=0.36). These effects occurred across all diagnoses and
      treatment formats. Improvements in shape and weight concerns and restraint were
      also greater in CBT than non-CBT interventions (g's=0.25, 0.24, 0.31,
      respectively) at post-treatment and follow-up. The magnitude of improvement in
      binge/purge symptoms was related to the magnitude of improvement in these
      maintaining mechanisms. Findings demonstrate that CBT has a specific effect in
      targeting the eating disorder maintaining mechanisms, and offers support to the
      underlying cognitive model. If changes in these variables during treatment are
      shown to be causal mechanisms, then these findings show that CBT, relative to non
      CBT interventions, is better able to modify these mechanisms.

PMID- 29378480
TI  - Irbesartan prevents sodium channel remodeling in a canine model of atrial
      fibrillation.
AB  - INTRODUCTION: Activation of the renin-angiotensin system (RAS) plays an important
      role in atrial electrical remodeling (AER). The purpose of the present study was
      to evaluate the effects of irbesartan on cardiac sodium current (INa) in a canine
      model of atrial fibrillation. MATERIALS AND METHODS: Eighteen dogs were
      randomized into sham, pacing or pacing+irbesartan groups ( n = 6 in each group).
      The dogs in the pacing and irbesartan group were paced at 500 bpm for two weeks.
      Irbesartan (60 mg.kg-1.d-1) was administered orally in the pacing+irbesartan
      groups. INa was recorded using the whole-cell patch clamp technique from canine
      atrial myocytes. The expressions of cardiac Na+ channels (Nav1.5) mRNA were semi
      quantified by reverse transcription-polymerase chain reaction. RESULTS: Our
      results showed that INa density and Nav1.5 mRNA expression in the pacing group
      decreased significantly ( p < 0.05 vs. sham). However, rapid atrial pacing had no
      effects on the half-activation voltage (V1/2act) and half-inactivation voltage
      (V1/2inact) of INa ( p > 0.05 vs. sham). Irbesartan significantly increased INa
      densities and gene expression and hyperpolarized V1/2act without concomitant
      changes in V1/2inact. CONCLUSIONS: Irbesartan significantly increased INa
      densities, which contributed to improving intra-atrial conduction and prevented
      the induction and promotion of AF in atrial pacing dogs.

PMID- 29378482
TI  - Longevity Escape Velocity Medicine: A New Medical Specialty for Longevity?

PMID- 29378483
TI  - Mapping the central effects of (+/-)-ketamine and traxoprodil using
      pharmacological magnetic resonance imaging in awake rats.
AB  - Major depressive disorder is a leading cause of disability globally. Improvements
      in the efficacy of antidepressant therapy are needed as a high proportion (>40%)
      of individuals with major depressive disorder fail to respond adequately to
      current treatments. The non-selective N-methyl-D-aspartate receptor channel
      blocker, (+/-)-ketamine, has been reported to produce a rapid and long-lasting
      antidepressant response in treatment-resistant major depressive disorder
      patients, which provides a unique opportunity for investigation of mechanisms
      that mediate its therapeutic effect. Efforts have also focused on the development
      of selective N-methyl-D-aspartate receptor subtype 2B antagonists which may
      retain antidepressant activity but have lower potential for
      dissociative/psychotomimetic effects. In the present study, we examined the
      central nervous system effects of acute, intravenous administration of (+/-)
      ketamine or the N-methyl-D-aspartate receptor subtype 2B antagonist, traxoprodil,
      in awake rats using pharmacological magnetic resonance imaging. The study
      contained five treatment groups: vehicle, 3 mg/kg (+/-)-ketamine, and three doses
      of traxoprodil (0.3 mg/kg, 5 mg/kg, and 15 mg/kg). Non-linear model fitting was
      performed on the temporal hemodynamic pharmacological magnetic resonance imaging
      data to generate brain activation maps as well as regional responses based on
      blood oxygen level dependent signal changes for group analysis. Traxoprodil at 5
      mg/kg and 15 mg/kg produced a dose-dependent pharmacological magnetic resonance
      imaging signal in rat forebrain regions with both doses achieving >80% N-methyl-D
      aspartate receptor subtype 2B occupancy determined by ex vivo [3H]Ro 25-6981
      binding. The middle dose of traxoprodil (5 mg/kg) generated region-specific
      activations in medial prefrontal cortex, ventral orbital cortex, and anterior
      cingulate cortex whereas the high dose (15 mg/kg) produced a widespread
      pharmacological magnetic resonance imaging response in both cortical and
      subcortical brain regions which was similar to that produced by (+/-)-ketamine (3
      mg/kg, intravenous).

PMID- 29378485
TI  - Treatment of lower urinary tract symptoms/benign prostatic hyperplasia and
      erectile dysfunction.
AB  - This article summarizes years of challenging research on erectile dysfunction
      (ED), a condition that has an important social and cultural relevance.
      Preclinical and clinical research progress has led to new therapeutic approaches
      to ED in patients with different comorbidities and particularly in those with low
      urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH). These goals
      were possible only by combined work of specialists and researchers of different
      and intertwined medical disciplines. Currently, tadalafil (5 mg/d) is the best
      choice; other phosphodiesterase-5 inhibitors (PDE5i) are not included among
      options, despite the growing evidence of therapeutic effects. Different regimens
      of tadalafil may be prescribed based on patient needs, severity of LUTS/BPH - ED
      profile, and clinical experience. An integrated approach is necessary to choose
      for a combined therapy with PDE5i and alpha-blockers following urological and
      cardiac counseling in terms of outcomes and adverse effects.

PMID- 29378486
TI  - Incremental burden of type 2 diabetes in patients experiencing cardiovascular
      hospitalizations.
AB  - OBJECTIVE: To evaluate the incremental economic burden of type 2 diabetes in
      patients experiencing cardiovascular (CV) hospitalizations. RESEARCH DESIGN AND
      METHODS: Adults with >=1 CV hospitalization were identified using a US-based
      healthcare claims database from 1 July 2011 to 30 June 2014. Outcomes for
      patients surviving the index hospitalization were compared between patients with
      vs. without type 2 diabetes (cohorts were identified in the pre-index period).
      Subsequent CV hospitalizations were evaluated using Cox proportional hazards
      models. All-cause and CV-related healthcare resource utilization (HCRU) and costs
      captured on a per-patient per-month (PPPM) basis during a variable follow-up
      period were evaluated using appropriate multivariable regression models. RESULTS:
      Of 316,207 patients with >=1 CV hospitalization, 23% had comorbid type 2
      diabetes. The mean age +/- SD was 62.6 +/- 12.3 years and 64.4% were male. During
      follow-up, the type 2 diabetes cohort had a 19% higher risk of subsequent CV
      hospitalizations compared to the non-type-2-diabetes cohort (p < .001). This
      difference in risk was highest in patients aged 35-44 years. Subsequent all-cause
      hospitalizations for the type 2 diabetes cohort were longer (mean length of stay,
      6.7 vs. 6.3 days; p < .001), with higher total bed-days PPPM (mean, 0.52 vs.
      0.43; p < .001), compared to the non-type-2-diabetes cohort. The type 2 diabetes
      cohort had a significantly higher incremental cost for both the index CV
      hospitalization (mean cost difference, $1046; p < .001) and all-cause costs PPPM
      following discharge (mean cost difference, $749; p < .001). CONCLUSIONS: Comorbid
      type 2 diabetes was associated with an increased risk of subsequent CV
      hospitalizations and higher costs and HCRU during the follow-up period.

PMID- 29378484
TI  - The relationship between ACE/AGT gene polymorphisms and the risk of diabetic
      retinopathy in Chinese patients with type 2 diabetes.
AB  - AIMS: This study aims to investigate the association between renin-angiotensin
      system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with
      type 2 diabetes. METHODS: We consecutively included 1491 patients for the
      assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146
      patients without retinopathy (DNR). Albuminuria was defined by urine albumin
      creatinine ratio and albumin excretion rate. RESULTS: Compared with the NDR
      patients, the DR cases displayed a higher proportion of diabetic nephropathy
      (32.68% vs. 6.52%, chi2 = 150.713, p < 0.001). The DR cases and DNR individuals
      did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T
      (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of
      DD (chi2 = 4.181, p = 0.041), but no significant difference exists in the other
      stratified BMI and hypertension analyses (all p > 0.05). Binary logistic
      regression displays that the association of the ACE and AGT gene polymorphisms in
      DR patients is not significant after adjusting for confounding covariates in all
      the comparisons. CONCLUSIONS: The ACE and AGT gene polymorphisms are not
      associated with the progress of diabetes developing into retinopathy in Chinese
      patients with type 2 diabetes. However, more investigations are needed to further
      prove the association.

PMID- 29378487
TI  - Incidence, Risk Factors, and Outcome of Acute Kidney Injury in Neurocritical
      Care.
AB  - PURPOSE: Acute kidney injury (AKI) is a severe complication in medical and
      surgical intensive care units accounting for a high morbidity and mortality.
      Incidence, risk factors, and prognostic impact of this deleterious condition are
      well established in this setting. Data concerning the neurocritically ill
      patients is scarce. Therefore, aim of this study was to determine the incidence
      of AKI and elucidate risk factors in this special population. METHODS: Patients
      admitted to a specialized neurocritical care unit between 2005 and 2011 with a
      length of stay above 48 hours were analyzed retrospectively for incidence, cause,
      and outcome of AKI (AKI Network-stage >=2). RESULTS: The study population
      comprised 681 neurocritically ill patients from a mixed neurosurgical and
      neurological intensive care unit. The prevalence of chronic kidney disease (CKD)
      was 8.4% (57/681). Overall incidence of AKI was 11.6% with 36 (45.6%) patients
      developing dialysis-requiring AKI. Sepsis was the main cause of AKI in nearly 50%
      of patients. Acute kidney injury and renal replacement therapy are independent
      predictors of worse outcome (hazard ratio [HR]: 3.704; 95% confidence interval
      [CI]: 1.867-7.350; P < .001; and HR: 2.848; CI: 1.301-6.325; P = .009). Chronic
      kidney disease was the strongest independent risk factor (odds ratio: 12.473; CI:
      5.944-26.172; P < .001), whereas surgical intervention or contrast agents were
      not associated with AKI. CONCLUSIONS: Acute kidney injury in neurocritical care
      has a high incidence and is a crucial risk factor for mortality independently of
      the underlying neurocritical condition. Sepsis is the main cause of AKI in this
      setting. Therefore, careful prevention of infectious complications and
      considering CKD in treatment decisions may lower the incidence of AKI and hereby
      improve outcome in neurocritical care.

PMID- 29378488
TI  - Commentary on Martinez-Mendez D. et al. Intra-articular distal radius fractures
      in elderly patients: a randomized prospective study of casting versus volar
      plating.

PMID- 29378491
TI  - Sixth annual Paul R. Manske Award for the best upper-extremity congenital
      research manuscript.

PMID- 29378493
TI  - Hand surgery in South Africa.

PMID- 29378492
TI  - Why and how to seek hand surgery training abroad.

PMID- 29378494
TI  - Letter about a Published Paper.

PMID- 29378496
TI  - Nutraceuticals to promote neuronal plasticity in response to corticosterone
      induced stress in human neuroblastoma cells.
AB  - OBJECTIVES: To search for novel compounds that will protect neuronal cells under
      stressed conditions that may help to restore neuronal plasticity. METHODS: A
      model of corticosterone (CORT)-induced stress in human neuroblastoma cells (SH
      SY5Y) was used to compare the efficacy of 6 crude extracts and 10 pure compounds
      (6 polyphenols, 2 carotenoids, 1 amino acid analogue, and 1 known antidepressant
      drug) to increase neuronal plasticity and to decrease cytotoxicity. RESULTS:
      Astaxanthin (among pure compounds) and phlorotannin extract of Fucus vesiculosus
      (among crude extracts) showed a maximum increase in cell viability in the
      presence of excess CORT. BDNF-VI mRNA expression in SH-SY5Y cells was
      significantly improved by pretreatment with quercetine, astaxanthin, curcumin,
      fisetin, and resveratrol. Among crude extracts, xanthohumol, phlorotannin extract
      (Ecklonia cava), petroleum ether extract (Nannochloropsis oculata), and
      phlorotannin extract (F. vesiculosus) showed a significant increase in BDNF-VI
      mRNA expression. CREB1 mRNA expression was significantly improved by astaxanthin,
      beta-carotene, curcumin, and fluoxetine whereas none of the crude extracts caused
      significant improvement. As an adjunct of fluoxetine, phlorotannin extract (F.
      vesiculosus), beta-carotene, and xanthohumol have resulted in significant
      improvement in BDNF-VI mRNA expression and CREB1 mRNA expression was
      significantly improved by phlorotannin extract (F. vesiculosus). Significant
      improvement in mature BDNF protein expression by phlorotannin extract (F.
      vesiculosus) and beta-carotene as an adjunct of fluoxetine confirm their
      potential to promote neuronal plasticity against CORT-induced stress. DISCUSSION:
      The carotenoids, flavonoids, namely quercetine, curcumin, and low molecular
      weight phlorotannin-enriched extract of F. vesiculosus may serve as potential
      neuroprotective agents promoting neuronal plasticity in vitro. Graphical
      abstract: Cascade of events associated with disturbed homeostatic balance of
      glucocorticoids and impact of phlorotannin extract (F. vesiculosus) and beta
      carotene in restoring neuronal plasticity. Abbreviation: TrKB, tropomyosin
      receptor kinase B; P-ERK, phosphorylated extracellular signal-related kinase;
      PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; Ca++/CaMK,
      calcium/calmodulin-dependent protein kinase; pCREB, phosphorylated cAMP response
      element-binding protein; CRE, cAMP response elements, CORT, corticosterone; and
      BDNF; brain-derived neurotrophic factor.

PMID- 29378497
TI  - Postoperative CEA is a better prognostic marker than CA19-9, hCGbeta or TATI
      after resection of colorectal liver metastases.
AB  - Liver metastases of colorectal cancer can be operated with a curative intent in
      selected cases. However, more than half of the patients have a recurrence. The
      aim of this study was to evaluate the prognostic and predictive value of
      carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), human
      chorionic gonadotropin beta (hCGbeta) and tumour-associated trypsin-inhibitor
      (TATI) in colorectal cancer patients before and 3 months after resection of liver
      metastases. Marker concentrations were determined in blood samples from 168
      colorectal cancer patients, who underwent liver resection between the years 1998
      and 2007 at Helsinki University Hospital, Finland. The samples were taken before
      and 3 months after curative resection. Increased concentrations of CEA (>5 ug/L)
      and hCGbeta (>1 pmol/L) 3 months after liver resection correlated with recurrence
      and impaired overall survival and increased CA19-9 (>26 kU/L) with impaired
      overall survival, but postoperative TATI was not prognostic. Preoperatively
      elevated CEA and CA19-9 correlated with impaired overall survival, but not with
      recurrence. Neither preoperative hCGbeta nor TATI was prognostic. In conclusion,
      CEA is a useful prognostic marker, when measured 3 months after resection of
      colorectal liver metastases. CA19-9 also has prognostic significance and may have
      additional value.

PMID- 29378498
TI  - Evaluating oil palm fresh fruit bunch processing in Nigeria.
AB  - Three routes of oil palm fresh fruit bunch (FFB) processing in Nigeria namely,
      industrial, small-scale and traditional were compared by means of determining
      fruit losses associated with each route. The fruits that are not recovered after
      each process were hand-picked and quantified in terms of crude palm oil (CPO),
      palm kernel (PK), mesocarp fibre (MF) and palm kernel shell (PKS). The energy
      value of empty fruit bunch (EFB), MF and PKS were used to determine the value of
      energy lost for each route. Additionally, the environmental implications of
      disposal of EFB were estimated, and socio-economics of the industrial and small
      scale routes were related. The analysis showed that 29, 18, 75 and 27 kg of CPO,
      PK, MF and PKS were lost for every 1000 kg of FFB processed with the industrial
      route, whereas 5.6, 3.2, 1.4 and 5.1 g were lost with the small-scale route,
      respectively. Approximately 89 kWh and 31 kWh more energy were lost from MF and
      PKS with the industrial route than the other two routes, respectively. An
      equivalent of 6670 tonnes carbon dioxide equivalent of methane and nitrogen oxide
      was released due to the disposal of 29,000 tonnes of EFB from one palm oil mill.
      The monetary value of lost CPO per 1000 kg of FFB processed in the industrial
      route is more than the labour cost of processing 1000 kg of FFB in the small
      scale route. The advantages of the industrial route are high throughput in terms
      of FFB processed per hour and high quality of CPO; however, high fruit loss is
      associated with it and therefore, the poorly threshed EFB is recommended to be
      fed into the small-scale route.

PMID- 29378499
TI  - Effects of the opening of the Qinghai-Tibet Railway on municipal solid waste
      management generation in Lhasa.
AB  - Lhasa, the capital of Tibet, is located on the Tibetan Plateau. Accelerated
      economic development and flourishing tourism resulting from the opening of the
      Qinghai-Tibet Railway (QTR) have increased solid waste generation and
      contamination in recent years. Using data from Lhasa Statistical Yearbooks and
      previous studies, this study estimates the future population of permanent
      residents and tourists using the least squares method to extrapolate the
      population from 2015-2025, and evaluates the effects of the QTR on municipal
      solid waste (MSW) generation in Lhasa and estimates future MSW generation. There
      were approximately 1.35 million tourists in 2008 when the QTR had been operating
      for 2 years and MSW generation was approximately 470 tons per day. The amount of
      MSW generated increased dramatically with time after opening the QTR. This study
      estimates that MSW generation will reach 962 tons per day in 2025. Due to the
      existence of the QTR, increasing numbers of people are traveling to Lhasa, and
      tourism has driven the development of the local economy. During the studies, the
      proportion of MSW produced by tourists increased from 2.99% to 20.06%, and it is
      estimated that it will increase to 33.49% in 2025. If the current trend
      continues, Lhasa will face significant challenges from garbage disposal. This
      study analyzes the current situation of urban garbage treatment in Lhasa, and it
      suggests several options for improvement to MSW generation, transportation
      equipment, disposal, and resource recycling.

PMID- 29378500
TI  - Solid-phase partitioning of mercury in artisanal gold mine tailings from selected
      key areas in Mindanao, Philippines, and its implications for mercury
      detoxification.
AB  - The solid-phase partitioning of mercury could provide necessary data in the
      identification of remediation techniques in contaminated artisanal gold mine
      tailings. This study was conducted to determine the total mercury content of mine
      wastes and identify its solid-phase partitioning through selective sequential
      extraction coupled with cold vapour atomic absorption spectroscopy. Samples from
      mine tailings and the carbon-in-pulp (CIP) process were obtained from selected
      key areas in Mindanao, Philippines. The results showed that mercury use is still
      prevalent among small-scale gold miners in the Philippines. Tailings after ball
      mill-gravity concentration (W-BM and Li-BM samples) from Mt Diwata and Libona
      contained high levels of mercury amounting to 25.024 and 6.5 mg kg-1,
      respectively. The most prevalent form of mercury in the mine tailings was
      elemental/amalgamated mercury, followed by water soluble, exchangeable, organic
      and strongly bound phases, respectively. In contrast, mercury content of carbon
      in-pulp residues were significantly lower at only 0.3 and 0.06 mg kg-1 for P-CIP
      (Del Pilar) and W-CIP (Mt Diwata), respectively. The bulk of mercury in P-CIP
      samples was partitioned in residual fraction while in W-CIP samples, water
      soluble mercury predominated. Overall, this study has several important
      implications with regards to mercury detoxification of contaminated mine tailings
      from Mindanao, Philippines.

PMID- 29378501
TI  - Comparative Proteomic Analysis of Liver Steatosis and Fibrosis after Oral
      Hepatotoxicant Administration in Sprague-Dawley Rats.
AB  - The past decade has seen an increase in the development and clinical use of
      biomarkers associated with histological features of liver disease. Here, we
      conduct a comparative histological and global proteomics analysis to identify
      coregulated modules of proteins in the progression of hepatic steatosis or
      fibrosis. We orally administered the reference chemicals bromobenzene (BB) or
      4,4'-methylenedianiline (4,4'-MDA) to male Sprague-Dawley rats for either 1
      single administration or 5 consecutive daily doses. Livers were preserved for
      histopathology and global proteomics assessment. Analysis of liver sections
      confirmed a dose- and time-dependent increase in frequency and severity of
      histopathological features indicative of lipid accumulation after BB or fibrosis
      after 4,4'-MDA. BB administration resulted in a dose-dependent increase in the
      frequency and severity of inflammation and vacuolation. 4,4'-MDA administration
      resulted in a dose-dependent increase in the frequency and severity of periportal
      collagen accumulation and inflammation. Pathway analysis identified a time
      dependent enrichment of biological processes associated with steatogenic or
      fibrogenic initiating events, cellular functions, and toxicological states.
      Differentially expressed protein modules were consistent with the observed
      histology, placing physiologically linked protein networks into context of the
      disease process. This study demonstrates the potential for protein modules to
      provide mechanistic links between initiating events and histopathological
      outcomes.

PMID- 29378502
TI  - Facial anthropometric measurements in Iranian male workers using Digimizer
      version 4.1.1.0 image analysis software: a pilot study.
AB  - OBJECTIVE: Craniometry is a subset of anthropometry, which measures the
      anatomical sizes of the head and face (craniofacial indicators). These dimensions
      are used in designing devices applied in the facial area, including respirators.
      This study was conducted to measure craniofacial dimensions of Iranian male
      workers required for face protective equipment design. METHODS: In this study,
      facial anthropometric dimensions of 50 randomly selected Iranian male workers
      were measured by photographic method and Digimizer version 4.1.1.0. Ten facial
      dimensions were extracted from photographs and measured by Digimizer version
      4.1.1.0. Mean, standard deviation and 5th, 50th and 95th percentiles for each
      dimension were determined and the relevant data bank was established. RESULTS:
      The anthropometric data bank for the 10 dimensions required for respirator design
      was provided for the target group with photo-anthropometric methods. The results
      showed that Iranian face dimensions were different from those of other nations
      and ethnicities. CONCLUSIONS: In this pilot study, anthropometric dimensions
      required for half-mask respirator design for Iranian male workers were measured
      by Digimizer version 4.1.1.0. The obtained anthropometric tables could be useful
      for the design of personal face protective equipment.

PMID- 29378503
TI  - Editorial: Bioactive Fungal Metabolites.

PMID- 29378504
TI  - Preface.

PMID- 29378505
TI  - Editorial: Applications of Medicinal Bioinorganic Chemistry.

PMID- 29378506
TI  - Editorial: Recent Trends in Anticancer Drug Development: Challenges and
      Opportunities.

PMID- 29378507
TI  - Editorial: Microwave-induced Organic Reactions Toward Biologically Active
      Molecules.

PMID- 29378508
TI  - Memory profiles in Down syndrome across development: a review of memory abilities
      through the lifespan.
AB  - Down syndrome (DS) is associated with a variety of cognitive impairments, notably
      memory impairments. Due to the high prevalence rates of early-onset dementia
      associated with DS, it is imperative to understand the comprehensive development
      of memory impairments beginning in childhood and into adulthood, as this may help
      researchers identify precursors of dementia at earlier stages of development and
      pinpoint targets for memory intervention. The current paper provides a
      systematic, developmentally focused review of the nature of memory difficulties
      in DS across the lifespan. Specifically, this review summarizes what is known
      about long-term, short-term, and working memory abilities (distinguishing between
      verbal and nonverbal modalities) in DS, compared to both mental age-matched
      typically developing peers and individuals with other forms of intellectual
      disability (ID) at three developmental stages (i.e., preschool, adolescence, and
      adulthood). Additionally, this review examines the degree of impairment reported
      relative to typically developing mental age-matched peers in the existing
      literature by examining effect size data across memory domains as a function of
      age. With few exceptions, memory abilities were impaired across the lifespan
      compared to mental age-matched typically developing peers. Relative to other
      groups with ID, research findings are mixed. Our review of the literature
      identified a scarcity of memory studies in early childhood, particularly for STM
      and WM. In adulthood, research was limited in the LTM and WM domains and very
      little research has compared memory abilities in older adults with DS to those
      with typical development. Looking to the future, longitudinal studies could
      provide a better understanding of the developmental trajectory of memory
      abilities in DS, and the possible associations between memory abilities and real
      world functioning. This research could ultimately inform interventions to improve
      independence and overall quality of life for those with DS and their families.

PMID- 29378509
TI  - Quantitative or qualitative transcriptional diagnostic signatures? A case study
      for colorectal cancer.
AB  - BACKGROUND: Due to experimental batch effects, the application of a quantitative
      transcriptional signature for disease diagnoses commonly requires inter-sample
      data normalization, which would be hardly applicable under common clinical
      settings. Many cancers might have qualitative differences with the non-cancer
      states in the gene expression pattern. Therefore, it is reasonable to explore the
      power of qualitative diagnostic signatures which are robust against experimental
      batch effects and other random factors. RESULTS: Firstly, using data of technical
      replicate samples from the MicroArray Quality Control (MAQC) project, we
      demonstrated that the low-throughput PCR-based technologies also exist large
      measurement variations for gene expression even when the samples were measured in
      the same test site. Then, we demonstrated the critical limitation of low
      stability for classifiers based on quantitative transcriptional signatures in
      applications to individual samples through a case study using a support vector
      machine and a naive Bayesian classifier to discriminate colorectal cancer tissues
      from normal tissues. To address this problem, we identified a signature
      consisting of three gene pairs for discriminating colorectal cancer tissues from
      non-cancer (normal and inflammatory bowel disease) tissues based on within-sample
      relative expression orderings (REOs) of these gene pairs. The signature was well
      verified using 22 independent datasets measured by different microarray and
      RNA_seq platforms, obviating the need of inter-sample data normalization.
      CONCLUSIONS: Subtle quantitative information of gene expression measurements
      tends to be unstable under current technical conditions, which will introduce
      uncertainty to clinical applications of the quantitative transcriptional
      diagnostic signatures. For diagnosis of disease states with qualitative
      transcriptional characteristics, the qualitative REO-based signatures could be
      robustly applied to individual samples measured by different platforms.

PMID- 29378512
TI  - Is perceived intolerance to milk and wheat associated with the corresponding IgG
      and IgA food antibodies? A cross sectional study in subjects with morbid obesity
      and gastrointestinal symptoms.
AB  - BACKGROUND: Serum IgG and IgA food antibodies have been used for dietary advice
      to subjects with gastrointestinal symptoms and perceived food intolerance, but
      the role of these antibodies in mediating intolerance is controversial. The
      present study investigated associations between perceived gastrointestinal
      intolerance to milk-or wheat and the corresponding s-IgG and s-IgA food
      antibodies in subjects with morbid obesity. METHODS: Subjects with morbid obesity
      (BMI >= 40 kg/m2 or >=35 kg/m2 with obesity-related complications) were included.
      Irritable Bowel Syndrome (IBS) was diagnosed based on the Rome III criteria.
      Severity of specific gastrointestinal symptoms were measured with the
      Gastrointestinal Symptom Rating Scale (GSRS)-IBS. S-IgG against cow's milk,
      cheese, wheat and gluten, and s-IgA against casein and gliadin were measured.
      RESULTS: Ninety-seven subjects (80 females) with mean age 45 (SD 8.4) years were
      included, 70 had gastrointestinal complaints, 25 had IBS, and 22 and 20 reported
      milk- and wheat- intolerance respectively. There were no significant differences
      in serum concentrations or proportions of subjects above defined cut-off values
      for the antibodies between subjects with and without gastrointestinal complaints.
      In the group with gastrointestinal complaints, no significant differences were
      found between subjects with and without perceived food intolerance. Except for a
      significant correlation between IgG against cheese and GSRS-diarrhea (Rho: -0.25,
      P = 0.04), no significant correlations were found between the antibodies and type
      or degree of gastrointestinal symptoms, including IBS. CONCLUSIONS: The study
      showed no associations between perceived milk or wheat intolerance and the
      corresponding s-IgG and s-IgA food antibodies in subjects with morbid obesity.

PMID- 29378511
TI  - Integrated omics data of two annual ryegrass (Lolium multiflorum L.) genotypes
      reveals core metabolic processes under drought stress.
AB  - BACKGROUND: Annual ryegrass (Lolium multiflorum L.) is a commercially important,
      widely distributed forage crop that is used in the production of hay and silage
      worldwide. Drought has been a severe environmental constraint in its production.
      Nevertheless, only a handful of studies have examined the impact of short-term
      drought stress on annual ryegrass. The aim of this study was to explore how
      stress-induced core metabolic processes enhance drought tolerance, or adaptation
      to drought, in annual ryegrass. RESULTS: We profiled the transcriptomes,
      proteomes, and metabolomes of two annual ryegrass genotypes: the drought
      resistant genotype "Abundant 10" and drought-susceptible genotype "Adrenalin 11."
      We identified differentially expressed metabolites and their corresponding
      proteins and transcripts that are involved in 23 core metabolic processes, in
      response to short-term drought stress. Protein-gene-metabolite correlation
      networks were built to reveal the relationships between the expression of
      transcripts, proteins, and metabolites in drought-resistant annual ryegrass.
      Furthermore, integrated metabolic pathways were used to observe changes in
      enzymes corresponding with levels of amino acids, lipids, carbohydrate
      conjugates, nucleosides, alkaloids and their derivatives, and pyridines and their
      derivatives. The resulting omics data underscored the significance of 23 core
      metabolic processes on the enhancement of drought tolerance or adaptation to
      drought in annual ryegrass. CONCLUSIONS: The regulatory networks were inferred
      using MCoA and correlation analysis to reveal the relationships among the
      expression of transcripts, proteins, and metabolites that highlight the
      corresponding elements of these core metabolic pathways. Our results provide
      valuable insight into the molecular mechanisms of drought resistance, and
      represent a promising strategy toward the improvement of drought tolerance in
      annual ryegrass.

PMID- 29378513
TI  - New anthropometric indices or old ones: which perform better in estimating
      cardiovascular risks in Chinese adults.
AB  - BACKGROUND: Various anthropometric indices can be used to estimate obesity, and
      it is important to determine which one is the best in predicting the risk of
      coronary heart disease (CHD) and to define the optimal cut-off point for the best
      index. METHODS: This cross-sectional study investigated a consecutive sample of
      11,247 adults, who had lived in rural areas of China and were older than 35 years
      of age. Eight obesity indices, including the body mass index (BMI), waist
      circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR),
      abdominal volume index (AVI), body adiposity index (BAI), body roundness index
      (BRI) and a body shape index (ABSI) were investigated. The risk of CHD was
      evaluated by the 10-year coronary event risk (Framingham risk score). Receiver
      operating characteristic (ROC) curve analyses were used to evaluate the
      predictive ability of the obesity indices for CHD risk. RESULTS: Of the whole
      population, 3636 (32.32%) participants had a risk score higher than 10%. Those
      who suffered medium or high CHD risk were more likely to have higher mean
      anthropometric indices, except for BMI in males. In the multivariate-adjusted
      logistic regression, all these anthropometric measurements were statistically
      associated with CHD risk in males. After adjusting for all the possible
      confounders, these anthropometric measurements, except for ABSI, remained as
      independent indicators of CHD risk in females. According to the ROC analyses,
      ABSI provided the largest area under the curve (AUC) value in males, and BMI
      showed the lowest AUC value, with AUC varying from 0.52 to 0.60. WHtR and BRI
      provided the largest AUC value in female, and similarly, BMI showed the lowest
      AUC value, with AUC varying from 0.59 to 0.70. The optimal cut-off values were as
      follows: WHtR (females: 0.54), BRI (females: 4.21), and ABSI (males: 0.078).
      CONCLUSIONS: ABSI was the best anthropometric index for estimating CHD risk in
      males, and WHtR and BRI were the best indicators in females. Males should
      maintain an ABSI of less than 0.078, and females should maintain a WHtR of less
      than 0.54 or a BRI of less than 4.21.

PMID- 29378510
TI  - Transcriptomic profiling of Burkholderia phymatum STM815, Cupriavidus taiwanensis
      LMG19424 and Rhizobium mesoamericanum STM3625 in response to Mimosa pudica root
      exudates illuminates the molecular basis of their nodulation competitiveness and
      symbiotic evolutionary history.
AB  - BACKGROUND: Rhizobial symbionts belong to the classes Alphaproteobacteria and
      Betaproteobacteria (called "alpha" and "beta"-rhizobia). Most knowledge on the
      genetic basis of symbiosis is based on model strains belonging to alpha-rhizobia.
      Mimosa pudica is a legume that offers an excellent opportunity to study the
      adaptation toward symbiotic nitrogen fixation in beta-rhizobia compared to alpha
      rhizobia. In a previous study (Melkonian et al., Environ Microbiol 16:2099-111,
      2014) we described the symbiotic competitiveness of M. pudica symbionts belonging
      to Burkholderia, Cupriavidus and Rhizobium species. RESULTS: In this article we
      present a comparative analysis of the transcriptomes (by RNAseq) of B. phymatum
      STM815 (BP), C. taiwanensis LMG19424 (CT) and R. mesoamericanum STM3625 (RM) in
      conditions mimicking the early steps of symbiosis (i.e. perception of root
      exudates). BP exhibited the strongest transcriptome shift both quantitatively and
      qualitatively, which mirrors its high competitiveness in the early steps of
      symbiosis and its ancient evolutionary history as a symbiont, while CT had a
      minimal response which correlates with its status as a younger symbiont (probably
      via acquisition of symbiotic genes from a Burkholderia ancestor) and RM had a
      typical response of Alphaproteobacterial rhizospheric bacteria. Interestingly,
      the upregulation of nodulation genes was the only common response among the three
      strains; the exception was an up-regulated gene encoding a putative fatty acid
      hydroxylase, which appears to be a novel symbiotic gene specific to Mimosa
      symbionts. CONCLUSION: The transcriptional response to root exudates was
      correlated to each strain nodulation competitiveness, with Burkholderia phymatum
      appearing as the best specialised symbiont of Mimosa pudica.

PMID- 29378514
TI  - Integrated ovarian mRNA and miRNA transcriptome profiling characterizes the
      genetic basis of prolificacy traits in sheep (Ovis aries).
AB  - BACKGROUND: The highly prolific breeds of domestic sheep (Ovis aries) are
      globally valuable genetic resources for sheep industry. Genetic, nutritional and
      other environmental factors affect prolificacy traits in sheep. To improve our
      knowledge of the sheep prolificacy traits, we conducted mRNA-miRNA integrated
      profiling of ovarian tissues from two pure breeds with large (Finnsheep) vs.
      small (Texel) litter sizes and their F1 crosses, half of which were fed a
      flushing diet. RESULTS: Among the samples, 16,402 genes (60.6% known ovine genes)
      were expressed, 79 novel miRNAs were found, and a cluster of miRNAs on chromosome
      18 was detected. The majority of the differentially expressed genes between
      breeds were upregulated in the Texel with low prolificacy, owing to the flushing
      diet effect, whereas a similar pattern was not detected in the Finnsheep. F1 ewes
      responded similarly to Finnsheep rather than displaying a performance
      intermediate between the two pure breeds. CONCLUSIONS: The identification and
      characterization of differentially expressed genes and miRNAs in the ovaries of
      sheep provided insights into genetic and environmental factors affecting
      prolificacy traits. The three genes (CST6, MEPE and HBB) that were differentially
      expressed between the group of Finnsheep and Texel ewes kept in normal diet
      appeared to be candidate genes of prolificacy traits and will require further
      validation.

PMID- 29378515
TI  - The effects of an 8-week computerized cognitive training program in older adults:
      a study protocol for a randomized controlled trial.
AB  - BACKGROUND: Given the world's aging population, it is important to identify
      strategies that promote healthy cognitive aging and minimize cognitive decline.
      Currently, no curative pharmaceutical therapy exists for cognitive impairment and
      dementia. As a result, there is much interest in lifestyle approaches.
      Specifically, complex mental activity, such as cognitive training, may be a
      promising method to combat cognitive decline in older adults. As such, the
      industry of commercial computerized cognitive training (CCT) applications has
      rapidly grown in the last decade. However, the efficacy of these commercial
      products is largely not established. Moreover, exercise is a recognized strategy
      for promoting cognitive outcomes in older adults and may augment the efficacy of
      computerized cognitive training applications. Therefore, we propose a proof-of
      concept randomized controlled trial (RCT) to examine the effect of a commercial
      CCT program in community-dwelling older adults. METHODS: An 8-week RCT to examine
      the effect of a commercial CCT program, alone and preceded by a 15-min brisk
      walk, on cognitive function and explore the underlying neural mechanisms in
      adults aged 65-85 years old. Participants will be randomized to one of three
      intervention groups: 1) Computerized cognitive training (FBT); 2) A 15-min brisk
      walk followed by computerized cognitive training (Ex-FBT); or 3) A combination of
      educational classes, sham cognitive training, and balanced and tone exercises
      (active control, BAT). Participants in all intervention groups will attend three
      one-hour classes per week over the course of the intervention. Participants will
      be assessed at baseline, trial completion, and 1-year post study completion (1
      year follow-up). DISCUSSION: If results from this study show benefits for
      cognition at trial completion, CCT programs, alone or in combination with
      walking, might be a strategy to promote healthy cognitive aging in older adults.
      In addition, results from the 1-year follow-up measurement could provide
      important information regarding the long-term benefits of these CCT programs.
      TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration System: NCT02564809;
      registered September 1, 2015.

PMID- 29378516
TI  - Left ventricular short-axis systolic function changes in patients with
      hypertrophic cardiomyopathy detected by two-dimensional speckle tracking imaging.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disease was
      characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, fiber
      disarray. The short-axis systolic function is important in left ventricle
      function. METHODS: Forty one healthy subjects and 37 HCM patients were enrolled
      for this research. Parasternal short-axis at the basal, middle, and apical levels
      were acquired by Echocardiography. The peak systolic circumferential strain of
      the endocardial, the middle and the epicardial layers, the peak systolic radial
      strain, and the peak systolic rotational degrees at different short-axis levels
      were measured by 2-dimensional speckle tracking imaging (2D-STI). RESULTS: The
      peak systolic circumferential strain of the septum and anterior walls in HCM
      patients was significantly lower than normal subjects. All of the peak systolic
      radial strain in HCM patients was significantly lower than normal subjects. The
      rotational degrees at the base and middle short-axis levels in HCM patients were
      larger than normal subjects. The interventricular septal thickness in end
      diastolic period correlated to the peak systolic circumferential strain of the
      septum wall. CONCLUSIONS: The short-axis systolic function was impaired in HCM
      patients. The peak circumferential systolic strain of the different layers, peak
      systolic radial strain and rotation degrees of the different short-axis levels
      detected by 2D-STI are very feasible for assessing the short-axis function in HCM
      patients.

PMID- 29378517
TI  - Cost-benefit analysis of aquaculture breeding programs.
AB  - BACKGROUND: Profitability of breeding programs is a key determinant in the
      adoption of selective breeding, and can be evaluated using cost-benefit analysis.
      There are many options to design breeding programs, with or without a multiplier
      tier. Our objectives were to evaluate different breeding program designs for
      aquaculture and to optimize the number of selection candidates for these
      programs. METHODS: The baseline was based on an existing breeding program for
      gilthead seabream, where improvement of the nucleus had priority over improvement
      of the multiplier tier, which was partly replaced once every 3 years. Alternative
      breeding programs considered were annual multiplier tier replacement, annual
      multiplier tier replacement with priority on improvement of the multiplier tier,
      and a program without a multiplier tier. Cost-benefit analyses were performed to
      compare breeding programs. The outcomes were used to describe relationships
      between profitability and the number of selection candidates, length of the time
      horizon, and production output, and to estimate the optimum numbers of selection
      candidates. RESULTS: The baseline breeding program was profitable after 5 years
      and reached a net present value of 2.9 million euro in year 10. All alternative
      programs were more profitable up to year 17. The program without a multiplier
      tier was the most profitable one up to year 22, followed by the program with
      annual multiplier tier replacement and nucleus priority. The optimum number of
      selection candidates increased with the length of the time horizon and production
      output. CONCLUSIONS: The baseline breeding program was profitable after 5 years.
      For a short time horizon, putting priority on improvement of the multiplier tier
      over the nucleus is more profitable than putting priority on nucleus improvement,
      and vice versa for a long time horizon. Use of a multiplier tier increases the
      delay between costs made for selection and resulting benefits. Thus, avoiding the
      use of a multiplier tier will increase the profitability of the breeding program
      in the short term. The optimum number of selection candidates increases with the
      length of the time horizon and production output. Using too many selection
      candidates relative to the optimum leads to less reduction in profitability than
      using too few selection candidates.

PMID- 29378519
TI  - Correction to: On the use of the outcome variable "small for gestational age"
      when gestational age is a potential mediator: a maternal asthma perspective.
AB  - CORRECTION: Following publication of the original article [1], the authors
      reported that the following four references in Table 2 are incorrect.

PMID- 29378518
TI  - Mobility and cognition at admission to the nursing home - a cross-sectional
      study.
AB  - BACKGROUND: Earlier studies show that the main reasons for admission to long-term
      nursing home care are cognitive impairment and functional impairments of
      activities of daily life. However, descriptive evidence of mobility is scant. The
      aims of this study were to describe mobility at admission to nursing homes and to
      assess the association between mobility and degree of dementia. METHODS: We
      included 696 residents at admission to 47 nursing homes in Norway. Inclusion
      criteria were expected stay for more than 4 weeks and 65 years or older. In
      addition, younger residents with dementia were included. Residents with life
      expectancy shorter than six weeks were excluded. Mobility was assessed using the
      Short Physical Performance Battery (SPPB) and the Nursing Home Life Space
      Diameter (NHLSD). The Clinical Dementia Rating Scale (CDR) was used to describe
      the degree of dementia. The associations between mobility and degree of dementia
      was analysed using the Chi-square and the Kruskal-Wallis test (KW-test). When the
      KW-test indicated a statistical significant difference, we proceeded with planned
      group comparisons with the Mann-Whitney U-test. In addition, we performed
      multiple linear regression analyses to control for potential confounders.
      RESULTS: Forty-three percent of the residents were not able to perform the
      balance test in SPPB. Twenty-four percent of the residents were not able to walk
      four meters, while only 17.6% had a walking speed of 0.83 m/s or higher. Sixty
      two percent of the residents were not able to rise from a chair or spent more
      than 60 s doing it. The median score on NHLSD area was 22 (IQR 17) and the median
      score on NHLSD dependency was 36 (IQR 26). Residents with severe dementia had
      significantly lower levels of mobility than residents with moderate dementia.
      Cognitive function was associated with SPPB and NHLSD dependency in the adjusted
      models. CONCLUSION: Nursing home residents form a frail, but heterogeneous group
      both in terms of cognition and mobility at admission. Mobility was negatively
      associated with cognitive function, and residents with severe dementia had
      significantly lower levels of mobility than residents with moderate dementia.

PMID- 29378520
TI  - Assessing runs of Homozygosity: a comparison of SNP Array and whole genome
      sequence low coverage data.
AB  - BACKGROUND: Runs of Homozygosity (ROH) are genomic regions where identical
      haplotypes are inherited from each parent. Since their first detection due to
      technological advances in the late 1990s, ROHs have been shedding light on human
      population history and deciphering the genetic basis of monogenic and complex
      traits and diseases. ROH studies have predominantly exploited SNP array data, but
      are gradually moving to whole genome sequence (WGS) data as it becomes available.
      WGS data, covering more genetic variability, can add value to ROH studies, but
      require additional considerations during analysis. RESULTS: Using SNP array and
      low coverage WGS data from 1885 individuals from 20 world populations, our aims
      were to compare ROH from the two datasets and to establish software conditions to
      get comparable results, thus providing guidelines for combining disparate
      datasets in joint ROH analyses. By allowing heterozygous SNPs per window, using
      the PLINK homozygosity function and non-parametric analysis, we were able to
      obtain non-significant differences in number ROH, mean ROH size and total sum of
      ROH between data sets using the different technologies for almost all
      populations. CONCLUSIONS: By allowing 3 heterozygous SNPs per ROH when dealing
      with WGS low coverage data, it is possible to establish meaningful comparisons
      between data using SNP array and WGS low coverage technologies.

PMID- 29378521
TI  - Detection and genotyping of Helicobacter pylori in saliva versus stool samples
      from asymptomatic individuals in Northeastern Thailand reveals intra-host tissue
      specific H. pylori subtypes.
AB  - BACKGROUND: Two-thirds of the world's population is thought to be infected by
      Helicobacter pylori. Although most people infected with H. pylori are
      asymptomatic, this pathogen is associated with several gastric pathologies
      including cancer. The risk factors for colonization are still unclear and the
      genetic diversity within individual hosts has never been clearly investigated.
      RESULT: This study determined the prevalence of, and explored risk factors for,
      H. pylori infection directly from paired saliva (n = 110) and stool (n = 110)
      samples from asymptomatic persons in Northeast Thailand. Samples were subjected
      to indirect immunofluorescence assay (IFA), 16S rRNA-based real-time PCR and vacA
      based semi-nested PCR. Partial vacA gene sequences of H. pylori were compared
      between saliva and stool samples. The overall prevalence of H. pylori infection
      in our asymptomatic study population was 64%. Age, gender, occupation and
      frequency of brushing teeth were not found to be associated with H. pylori
      colonization. The vacA gene was successfully sequenced from both saliva and stool
      samples of 12 individuals. For seven of these individuals, saliva and stool
      sequences fell into different clusters on a phylogenetic tree, indicating intra
      host genetic variation of H. pylori. CONCLUSION: This study reports a high
      prevalence of H. pylori infection in asymptomatic persons in this region of
      Thailand and demonstrates that genotypes (vacA gene sequences) of H. pylori may
      differ between the oral cavity and intestinal tract.

PMID- 29378522
TI  - Auditory repetition suppression alterations in relation to cognitive functioning
      in fragile X syndrome: a combined EEG and machine learning approach.
AB  - BACKGROUND: Fragile X syndrome (FXS) is a neurodevelopmental genetic disorder
      causing cognitive and behavioural deficits. Repetition suppression (RS), a
      learning phenomenon in which stimulus repetitions result in diminished brain
      activity, has been found to be impaired in FXS. Alterations in RS have been
      associated with behavioural problems in FXS; however, relations between RS and
      intellectual functioning have not yet been elucidated. METHODS: EEG was recorded
      in 14 FXS participants and 25 neurotypical controls during an auditory
      habituation paradigm using repeatedly presented pseudowords. Non-phased locked
      signal energy was compared across presentations and between groups using linear
      mixed models (LMMs) in order to investigate RS effects across repetitions and
      brain areas and a possible relation to non-verbal IQ (NVIQ) in FXS. In addition,
      we explored group differences according to NVIQ and we probed the feasibility of
      training a support vector machine to predict cognitive functioning levels across
      FXS participants based on single-trial RS features. RESULTS: LMM analyses showed
      that repetition effects differ between groups (FXS vs. controls) as well as with
      respect to NVIQ in FXS. When exploring group differences in RS patterns, we found
      that neurotypical controls revealed the expected pattern of RS between the first
      and second presentations of a pseudoword. More importantly, while FXS
      participants in the <= 42 NVIQ group showed no RS, the > 42 NVIQ group showed a
      delayed RS response after several presentations. Concordantly, single-trial
      estimates of repetition effects over the first four repetitions provided the
      highest decoding accuracies in the classification between the FXS participant
      groups. CONCLUSION: Electrophysiological measures of repetition effects provide a
      non-invasive and unbiased measure of brain responses sensitive to cognitive
      functioning levels, which may be useful for clinical trials in FXS.

PMID- 29378523
TI  - Late presentation for HIV care in Southwest Ethiopia in 2003-2015: prevalence,
      trend, outcomes and risk factors.
AB  - BACKGROUND: Early presentation for HIV care is vital as an initial tread in the
      UNAIDS 90-90-90 targets. However, late presentation for HIV care (LP) challenges
      achieving the targets. This study assessed the prevalence, trends, outcomes and
      risk factorsfor LP. METHODS: A 12 year retrospective cohort study was conducted
      using electronic medical records extracted from an antiretroviral therapy (ART)
      clinic at Jimma University Teaching Hospital. LP for children refers to moderate
      or severe immune-suppression, or WHO clinical stage 3 or 4 at the time of first
      presentation to the ART clinics. LP for adults refers to CD4 lymphocyte count of
      < 200 cells/ MUl and < 350 cells/MUl irrespective of clinical staging, or WHO
      clinical stage 3 or 4 irrespective of CD4 count at the time of first presentation
      to the ART clinics. Binary logistic regression was used to identify factors that
      were associated with LP, and missing data were handled using multiple
      imputations. RESULTS: Three hundred ninety-nine children and 4900 adults were
      enrolled in ART care between 2003 and 15. The prevalence of LP was 57% in
      children and 66.7% in adults with an overall prevalence of 65.5%, and the 10-year
      analysis of LP showed upward trends. 57% of dead children, 32% of discontinued
      children, and 97% of children with immunological failure were late presenters for
      HIV care. Similarly, 65% of dead adults, 65% of discontinued adults, and 79% of
      adults with immunological failure presented late for the care. Age between 25- <
      50 years (AOR = 0.4,95% CI:0.3-0.6) and 50+ years (AOR = 0.4,95% CI:0.2-0.6),
      being female (AOR = 1.2, 95% CI: 1.03-1.5), having Tb/HIV co-infection (AOR =
      1.6, 95% CI: 1.09-2.1), having no previous history of HIV testing (AOR = 1.2, 95%
      CI: 1.1-1.4), and HIV care enrollment period in 2012 and after (AOR = 0.8, 95%
      CI: 0.7-0.9) were the factors associated with LP for Adults. For children, none
      of the factors were associated with LP. CONCLUSIONS: The prevalence of LP was
      high in both adults and children. The majority of both children and adults who
      presented late for HIV care had died and developed immunological failure.
      Effective programs should be designed and implemented to tackle the gap in timely
      HIV care engagement.

PMID- 29378524
TI  - Therapeutic preferences and outcomes in newly diagnosed patients with Crohn's
      diseases in the biological era in Hungary: a nationwide study based on the
      National Health Insurance Fund database.
AB  - BACKGROUND: Accelerated treatment strategy, including tight disease control and
      early aggressive therapy with immunosuppressives (IS) and biological agents have
      become increasingly common in inflammatory bowel disease (IBD). The aim of the
      present study was to estimate the early treatment strategy and outcomes in newly
      diagnosed patients with Crohn's disease (CD) between 2004 and 2008 and 2009-2015
      in the whole IBD population in Hungary based on the administrative database of
      the National Health Insurance Fund (OEP). METHODS: We used the administrative
      database of the OEP, the only nationwide state-owned health insurance provider in
      Hungary. Patients were identified through previously reported algorithms using
      the ICD-10 codes for CD in the out-, inpatient (medical, surgical) non-primary
      care records and drug prescription databases between 2004 and 2015. Patients were
      stratified according to the year of diagnosis and maximum treatment steps during
      the first 3 years after diagnosis. RESULTS: A total of 6173 (male/female:
      46.12%/53.87%) newly diagnosed CD patients with physician-diagnosed IBD were
      found in the period of 2004-2015. The use of 5-ASA and steroids remained common
      in the biological era, while immunosuppressives and biologicals were started
      earlier and became more frequent among patients diagnosed after 2009. The
      probability of biological therapy was 2.9%/6.4% and 8.4%/13.7% after 1 and 3
      years in patients diagnosed in 2004-2008/2009-2015. The probability of
      hospitalization in the first 3 years after diagnosis was different before and
      after 2009, according to the maximal treatment step (overall 55.7%vs. 47.4% (p =
      0.001), anti-TNF: 73%vs. 66.7% (p = 0.103), IS: 64.6% vs. 56.1% (p = 0.001),
      steroid: 44.2%vs. 36.8% (p < 0.007), 5-ASA: 32.6% vs. 26.7% p = 0.157)). In
      contrast, surgery rates were not significantly different in patients diagnosed
      before and after 2009 according to the maximum treatment step (overall
      16.0%vs.15.3%(p = 0.672) anti-TNF 26.7%vs.27.2% (p = 0.993), IS: 24.1%vs22.2% (p
      = 0.565), steroid 8.1%vs.7.9% (p = 0.896), 5-ASA 10%vs. 11% (p = 0.816)).
      CONCLUSIONS: IS and biological exposure became more frequent, while
      hospitalization decreased and surgery remained low but constant during the
      observation period. Use of steroids and 5-ASA remained high after 2009. The
      association between the maximal treatment step and hospitalization/surgery rates
      suggests that maximal treatment step can be regarded as proxy severity marker in
      patients with IBD.

PMID- 29378525
TI  - Developmental change in look durations predicts later effortful control in
      toddlers at familial risk for ASD.
AB  - BACKGROUND: Difficulties with executive functioning (EF) are common in
      individuals with a range of developmental disorders, including autism spectrum
      disorder (ASD). Interventions that target underlying mechanisms of EF early in
      development could be broadly beneficial, but require infant markers of such
      mechanisms in order to be feasible. Prospective studies of infants at high
      familial risk (HR) for ASD have revealed a surprising tendency for HR toddlers to
      show longer epochs of attention to faces than low-risk (LR) controls. In typical
      development, decreases in look durations towards the end of the first year of
      life are driven by the development of executive attention-a foundational
      component of EF. Here, we test the hypothesis that prolonged attention to visual
      stimuli (including faces) in HR toddlers reflects early differences in the
      development of executive attention. METHODS: In a longitudinal prospective study,
      we used eye-tracking to record HR and LR infants' looking behaviour to social and
      non-social visual stimuli at ages 9 and 15 months. At age 3 years, we assessed
      children with a battery of clinical research measures and collected parental
      report of effortful control (EC)-a temperament trait closely associated with EF
      and similarly contingent on executive attention. RESULTS: Consistent with
      previous studies, we found an attenuated reduction in peak look durations to
      faces between 9 and 15 months for the HR group compared with the LR group, and
      lower EC amongst the HR-ASD group. In line with our hypothesis, change in peak
      look duration to faces between 9 and 15 months was negatively associated with EC
      at age 3. CONCLUSIONS: We suggest that for HR toddlers, disruption to the early
      development of executive attention results in an attenuated reduction in looking
      time to faces. Effects may be more apparent for faces due to early biases to
      orient towards them; further, attention difficulties may interact with earlier
      emerging differences in social information processing. Our finding that prolonged
      attention to faces may be an early indicator of disruption to the executive
      attention system is of potential value in screening for infants at risk for later
      EF difficulties and for evaluation of intervention outcomes.

PMID- 29378526
TI  - Saving babies' lives project impact and results evaluation (SPiRE): a mixed
      methodology study.
AB  - BACKGROUND: Reducing stillbirth and early neonatal death is a national priority
      in the UK. Current evidence indicates this is potentially achievable through
      application of four key interventions within routine maternity care delivered as
      the National Health Service (NHS) England's Saving Babies' Lives care bundle.
      However, there is significant variation in the degree of implementation of the
      care bundle between and within maternity units and the effectiveness in reducing
      stillbirth and improving service delivery has not yet been evaluated. This study
      aims to evaluate the impact of implementing the care bundle on UK maternity
      services and perinatal outcomes. METHODS: The Saving Babies' Lives Project Impact
      and Results Evaluation (SPiRE) study is a multicentre evaluation of maternity
      care delivered through the Saving Babies' Lives care bundle using both
      quantitative and qualitative methodologies. The study will be conducted in twenty
      NHS Hospital Trusts and will include approximately 100,000 births. It involves
      participation by both service users and care providers. To determine the impact
      of the care bundle on pregnancy outcomes, birth data and other clinical measures
      will be extracted from maternity databases and case-note audit from before and
      after implementation. Additionally, this study will employ questionnaires with
      organisational leads and review clinical guidelines to assess how resources,
      leadership and governance may affect implementation in diverse hospital settings.
      The cost of implementing the care bundle, and the cost per stillbirth avoided,
      will also be estimated as part of a health economic analysis. The views and
      experiences of service users and service providers towards maternity care in
      relation to the care bundle will be also be sought using questionnaires.
      DISCUSSION: This protocol describes a pragmatic study design which is necessarily
      limited by the availability of data and limitations of timescales and funding. In
      particular there was no opportunity to prospectively gather pre-intervention data
      or design a phased implementation such as a stepped-wedge study. Nevertheless
      this study will provide useful practice-based evidence which will advance
      knowledge about the processes that underpin successful implementation of the care
      bundle so that it can be further developed and refined. TRIAL REGISTRATION:
      www.clinicaltrials.gov NCT03231007 (26th July 2017).

PMID- 29378527
TI  - Inclusion of joint laxity, recurrent patellar dislocation, and short distal ulnae
      as a feature of Van Den Ende-Gupta syndrome: a case report.
AB  - BACKGROUND: Van Den Ende-Gupta Syndrome (VDEGS) is an extremely rare autosomal
      recessive syndrome with less than 20 reported families (approximately 40
      patients) in the worldwide literature. CASE PRESENTATION: We have assessed one
      consanguineous Saudi family with typical features of VDEGS. Two siblings were
      affected with almost identical features; including blepharophimosis,
      arachnodactyly, flexion contractures of the elbows, camptodactyly, slender ribs,
      hooked lateral clavicular ends, and bilateral radial head dislocations. Both
      patients had several unusual features; including joint laxity, flat feet,
      recurrent patellar dislocations, and bilateral short distal ulnae. Full
      sequencing of SCARF2 revealed a homozygous mutation c.773G > A (p. Cys258Tyr) in
      both affected children. The parents (both with no abnormalities) were
      heterozygous for the same mutation. CONCLUSION: Joint laxity, recurrent patellar
      dislocations, and short distal ulnae should be included as part of the clinical
      spectrum of VDEGS.

PMID- 29378528
TI  - Clinical outcomes of switching to aflibercept using a pro re nata treatment
      regimen in patients with neovascular age-related macular degeneration who
      incompletely responded to ranibizumab.
AB  - BACKGROUND: To assess the effect of switching patients previously incompletely
      treated with ranibizumab (RBZ) to aflibercept (AFL) using a pro re nata (PRN)
      treatment strategy in neovascular age-related macular degeneration (nvAMD).
      METHODS: A retrospective case series was conducted on patients who had persistent
      or recurrent intra- and/or sub-retinal fluid treated initially with RBZ and
      subsequently switched to AFL. The main outcome measures were best corrected
      visual acuity (BCVA) and central retinal thickness (CRT) measured at different
      stages of the study. Friedman analysis of variance and Wilcoxon test were used to
      examine differences in BCVA and CRT. RESULTS: Two hundred and seven eyes from 182
      patients were included. BCVA and CRT improved significantly initially following 3
      RBZ injections with a mean gain of 3.7 letters (p < 0.001) and a mean loss of 69
      MUm (p < 0.001) respectively. Following PRN RBZ therapy and immediately prior to
      switching to AFL (mean 129 weeks), there was a mean loss of 6.7 letters (p <
      0.001) BCVA and a mean gain of 24 MUm (p < 0.001) CRT. AFL loading resulted in a
      mean improvement of 0.7 letters (p = 0.28) BCVA and 55 MUm (p < 0.001) CRT. At
      final follow-up following AFL PRN therapy (mean 85 weeks), there was a mean loss
      of 8.9 letters (p < 0.001) BCVA and a mean gain of 12 MUm (p < 0.05) CRT.
      CONCLUSION: AFL loading resulted in a significant anatomical improvement but no
      significant change in visual acuity. However, the benefits of switching were
      gradually lost over time with AFL PRN dosing despite an increased injection rate
      when compared with RBZ PRN treatment. TRIAL REGISTRATION: Not applicable.

PMID- 29378529
TI  - Galectin-1 is a poor prognostic factor in patients with glioblastoma multiforme
      after radiotherapy.
AB  - BACKGROUND: Galectin-1, a radioresistance marker, was found in our previous study
      to be a prognostic factor for cervical cancer. The aim of current study is to
      determine the prognostic significance of the galectin-1 expression level in
      patients with glioblastoma multiforme (GBM) undergoing adjuvant radiotherapy
      (RT). METHODS: We included 45 patients with GBM who were treated with maximal
      safe surgical resection or biopsy alone followed by adjuvant RT of EQD2
      (equivalent dose in 2-Gy fractions) > or = 60 Gy for homogeneous treatment.
      Paraffin-embedded tissues acquired from the Department of Pathology were analyzed
      using immunohistochemical staining for galectin-1 expression. The primary
      endpoint was overall survival (OS). RESULTS: Patients with weak expression had a
      better median survival (27.9 months) than did those with strong expression (10.7
      months; p = 0.009). We compared characteristics between weak and strong galectin
      1 expression, and only the expression level of galectin-3 showed a correlation.
      The group with weak galectin-1 expression displayed a 3-year OS of 27.3% and a 3
      year cancer-specific survival (CSS) of 27.3%; these values were only 5.9% and
      7.6%, respectively, in the group with strong galectin-1 expression (p = 0.009 and
      0.020, respectively). Cox regression was used to confirm that the expression
      level of galectin-1 (weak vs. strong) is a significant factor of OS (p = 0.020)
      and CSS (p = 0.022). Other parameters, such as the expression level of galectin
      3, Eastern Cooperative Oncology Group (ECOG) performance, gender, surgical
      method, age >= 50 years, tumor size, or radiation field were not significant
      factors. CONCLUSION: The expression level of galectin-1 affects survival in
      patients with GBM treated with adjuvant RT. Future studies are required to
      analyze the effect of other factors, such as O(6)-methylguanine-DNA
      methyltransferase (MGMT)-promoter methylation status, in patients with weak and
      strong galectin-1 expression.

PMID- 29378530
TI  - Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and
      laser treatment in Type-1 and threshold retinopathy of prematurity (ROP).
AB  - BACKGROUND: Retinopathy of Prematurity (ROP) is one of the most common causes of
      childhood blindness worldwide. Comparisons of anti-VEGF and laser treatments in
      ROP are relatively lacking, and the data are scattered and limited. The objective
      of this meta-analysis is to compare the efficacy of both treatments in type-1 and
      threshold ROP. METHODS: A comprehensive literature search on ROP treatment was
      conducted using PubMed and Embase up to March 2017 in all languages. Major
      evaluation indexes were extracted from the included studies by two authors. The
      fixed-effects and random-effects models were used to measure the pooled
      estimates. The test of heterogeneity was performed using the Q statistic.
      RESULTS: Ten studies were included in this meta-analysis. Retreatment incidence
      was significantly increased for anti-VEGF (OR 2.52; 95% CI 1.37 to 4.66; P =
      0.003) compared to the laser treatment, while the incidences of eye complications
      (OR 0.29; 95% CI 0.10 to 0.82; P = 0.02) and myopia were significantly decreased
      with anti-VEGF compared to the laser treatment. However, there was no difference
      in the recurrence incidence (OR 1.86; 95% CI 0.37 to 9.40; P = 0.45) and time
      between treatment and retreatment (WMD 7.54 weeks; 95% CI 2.00 to 17.08; P =
      0.12). CONCLUSION: This meta-analysis indicates that laser treatment may be more
      efficacious than anti-VEGF treatment. However, the results of this meta-analysis
      also suggest that laser treatment may cause more eye complications and increase
      myopia. Large-scale prospective RCTs should be performed to assess the efficacy
      and safety of anti-VEGF versus laser treatment in the future.

PMID- 29378531
TI  - Variations of circulating cardiac biomarkers during and after anthracycline
      containing chemotherapy in breast cancer patients.
AB  - BACKGROUND: Over time, the chance of cure after the diagnosis of breast cancer
      has been increasing, as a consequence of earlier diagnosis, improved diagnostic
      procedures and more effective treatment options. However, oncologists are
      concerned by the risk of long term treatment side effects, including congestive
      heart failure (CHF). METHODS: In this study, we evaluated innovative circulating
      cardiac biomarkers during and after anthracycline-based neoadjuvant chemotherapy
      (NAC) in breast cancer patients. Levels of cardiac-specific troponins T (cTnT), N
      terminal natriuretic peptides (NT-proBNP), soluble ST2 (sST2) and 10 circulating
      microRNAs (miRNAs) were measured. RESULTS: Under chemotherapy, we observed an
      elevation of cTnT and NT-proBNP levels, but also the upregulation of sST2 and of
      4 CHF-related miRNAs (miR-126-3p, miR-199a-3p, miR-423-5p, miR-34a-5p). The
      elevations of cTnT, NT-proBNP, sST2 and CHF-related miRNAs were poorly
      correlated, suggesting that these molecules could provide different information.
      CONCLUSIONS: Circulating miRNA and sST2 are potential biomarkers of the
      chemotherapy-related cardiac dysfunction (CRCD). Nevertheless, further studies
      and long-term follow-up are needed in order to evaluate if these new markers may
      help to predict CRCD and to identify the patients at risk to later develop CHF.

PMID- 29378532
TI  - Intra-arterial ethanol embolization augments response to TACE for treatment of
      HCC with portal venous tumor thrombus.
AB  - BACKGROUND: The prognosis of hepatocellular carcinoma with portal vein tumor
      thrombus remains extremely poor. This pilot study aimed to evaluate the technical
      feasibility, effectiveness and safety of transcatheter chemoembolization for
      tumors in the liver parenchyma plus intra-arterial ethanol embolization for
      portal vein tumor thrombus. METHODS: A pilot study was carried out on 31 patients
      in the treatment group (transcatheter chemoembolization plus intra-arterial
      ethanol embolization) and 57 patients in the control group (transcatheter
      chemoembolization alone). Enhanced computed tomography/magnetic resonance images
      were repeated 4 weeks after the procedure to assess the response. Overall
      survival and complications were assessed until the patient died or was lost to
      follow-up. RESULTS: Median survival was 10.5 months in the treatment group (2.4
      +/- 1.7 courses) and 3.9 months in the control group (1.9 +/- 1 courses) (P =
      0.001). Patients in the treatment group had better overall survival (at 3, 6 and
      12 months, respectively), compared to patients in the control group (90.3% vs.
      59.6%, 64.5% vs. 29.8%, and 41.9% vs. 10.6%; p = 0.001). Furthermore, the rate of
      portal vein tumor thrombus regression was higher in the treatment group (93.1%)
      than in the control group (32.1%) (P < 0.001). CONCLUSIONS: Based on the results
      of this study, transcatheter chemoembolization combined with intra-arterial
      ethanol embolization may be more effective than transcatheter chemoembolization
      alone for treating hepatocellular carcinoma with portal vein tumor thrombus.
      Intra-arterial ethanol embolization for treating portal vein tumor thrombus is
      safe, feasible and prolongs overall survival.

PMID- 29378533
TI  - An advanced glioma cell invasion assay based on organotypic brain slice cultures.
AB  - BACKGROUND: The poor prognosis for glioblastoma patients is caused by the diffuse
      infiltrative growth pattern of the tumor. Therefore, the molecular and cellular
      processes underlying cell migration continue to be a major focus of glioblastoma
      research. Emerging evidence supports the concept that the tumor microenvironment
      has a profound influence on the functional properties of tumor cells.
      Accordingly, substantial effort must be devoted to move from traditional two
      dimensional migration assays to three-dimensional systems that more faithfully
      recapitulate the complex in vivo tumor microenvironment. METHODS: In order to
      mimic the tumor microenvironment of adult gliomas, we used adult organotypic
      brain slices as an invasion matrix for implanted, fluorescently labeled tumor
      spheroids. Cell invasion was imaged by confocal or epi-fluorescence microscopy
      and quantified by determining the average cumulative sprout length per spheroid.
      The tumor microenvironment was manipulated by treatment of the slice with small
      molecule inhibitors or using different genetically engineered mouse models as
      donors. RESULTS: Both epi-fluorescence and confocal microscopy were applied to
      precisely quantify cell invasion in this ex vivo approach. Usage of a red
      emitting membrane dye in addition to tissue clearing drastically improved epi
      fluorescence imaging. Preparation of brain slices from of a genetically
      engineered mouse with a loss of a specific cell surface protein resulted in
      significantly impaired tumor cell invasion. Furthermore, jasplakinolide treatment
      of either tumor cells or brain slice significantly reduced tumor cell invasion.
      CONCLUSION: We present an optimized invasion assay that closely reflects in vivo
      invasion by the implantation of glioma cells into organotypic adult brain slice
      cultures with a preserved cytoarchitecture. The diversity of applications
      including manipulation of the tumor cells as well as the microenvironment,
      permits the investigation of rate limiting factors of cell migration in a
      reliable context. This model will be a valuable tool for the discovery of the
      molecular mechanisms underlying glioma cell invasion and, ultimately, the
      development of novel therapeutic strategies.

PMID- 29378534
TI  - Vertebral fractures among breast cancer survivors in China: a cross-sectional
      study of prevalence and health services gaps.
AB  - BACKGROUND: Breast cancer survivors are at high risk for fracture due to cancer
      treatment-induced bone loss, however, data is scarce regarding the scope of this
      problem from an epidemiologic and health services perspective among Chinese women
      with breast cancer. METHODS: We designed a cross-sectional study comparing
      prevalence of vertebral fractures among age- and BMI-matched women from two
      cohorts. Women in the Breast Cancer Survivors cohort were enrolled from a large
      cancer hospital in Beijing. Eligibility criteria included age 50-70 years,
      initiation of treatment for breast cancer at least 5 years prior to enrollment,
      and no history of metabolic bone disease or bone metastases. Data collected
      included sociodemographic characteristics; fracture-related risk factors,
      screening and preventive measures; breast cancer history; and thoracolumbar x
      ray. The matched comparator group was selected from participants enrolled in the
      Peking Vertebral Fracture Study, an independent cohort of healthy community
      dwelling postmenopausal women from Beijing. RESULTS: Two hundred breast cancer
      survivors were enrolled (mean age 57.5 +/- 4.9 years), and compared with 200
      matched healthy women. Twenty-two (11%) vertebral fractures were identified among
      breast cancer survivors compared with 7 (3.5%) vertebral fractures in the
      comparison group, yielding an adjusted odds ratio for vertebral fracture of 4.16
      (95%CI 1.69-10.21, p < 0.01). The majority had early stage (85.3%) and estrogen
      and/or progesterone receptor positive (84.6%) breast cancer. Approximately half
      of breast cancer survivors reported taking calcium supplements, 6.1% reported
      taking vitamin D supplements, and only 27% reported having a bone density scan
      since being diagnosed with breast cancer. CONCLUSIONS: Despite a four-fold
      increased odds of prevalent vertebral fracture among Chinese breast cancer
      survivors in our study, rates of screening for osteoporosis and fracture risk
      were low reflecting a lack of standardization of care regarding cancer-treatment
      induced bone loss.

PMID- 29378535
TI  - Whole exome sequencing reveals a stop-gain mutation of PKD2 in an autosomal
      dominant polycystic kidney disease family complicated with aortic dissection.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common inherited kidney disorder characterized by progressive cyst formation and
      expansion in the kidneys, which culminates in end-stage renal disease. Aortic
      dissection is a rare vascular complication of ADPKD and related literature is
      currently limited. CASE PRESENTATION: In this report, we described a patient with
      asymptomatic Stanford B aortic dissection. Further investigation revealed a
      positive family history of ADPKD and normal renal function. Whole exome
      sequencing identified a stop-gain mutation c.1774C > T, p.Arg592Ter in the PKD2
      gene that segregated in the family. To our knowledge, this is the first report of
      ADPKD complicated with aortic dissection caused by PKD2 mutation. CONCLUSIONS:
      The case illustrates the importance of aorta imaging and molecular diagnosis in
      ADPKD patients in order to achieve early recognition of the deadly vascular
      complication.

PMID- 29378537
TI  - Comprehensive economic evaluation of thermotherapy for the treatment of cutaneous
      leishmaniasis in Colombia.
AB  - BACKGROUND: Cutaneous leishmaniasis causes a high disease burden in Colombia, and
      available treatments present systemic toxicity, low patient compliance,
      contraindications, and high costs. The purpose of this study was to estimate the
      cost-effectiveness of thermotherapy versus Glucantime in patients with cutaneous
      leishmaniasis in Colombia. METHODS: Cost-effectiveness study from an
      institutional perspective in 8133 incident cases. Data on therapeutic efficacy
      and safety were included, calculating standard costs; the outcomes were
      disability adjusted life years (DALYs) and the number of patients cured. The
      information sources were the Colombian Public Health Surveillance System, disease
      burden studies, and one meta-analysis of controlled clinical trials. Incremental
      cost-effectiveness was determined, and uncertainty was evaluated with tornado
      diagrams and Monte Carlo simulations. RESULTS: Thermotherapy would generate costs
      of US$ 501,621; the handling of adverse effects, US$ 29,224; and therapeutic
      failures, US$ 300,053. For Glucantime, these costs would be US$ 2,731,276, US$
      58,254, and US$ 406,298, respectively. With thermotherapy, the cost would be US$
      2062 per DALY averted and US$ 69 per patient cured; with Glucantime, the cost
      would be US$ 4241 per DALY averted and US$ 85 per patient cured. In Monte Carlo
      simulations, thermotherapy was the dominant strategy for DALYs averted in 67.9%
      of cases and highly cost-effective for patients cured in 72%. CONCLUSION: In
      Colombia, thermotherapy can be included as a cost-effective strategy for the
      management of cutaneous leishmaniasis. Its incorporation into clinical practice
      guidelines could represent savings of approximately US$ 10,488 per DALY averted
      and costs of US$ 116 per additional patient cured, compared to the use of
      Glucantime. These findings show the relevance of the incorporation of this
      treatment in our country and others with similar parasitological, clinical, and
      epidemiological patterns.

PMID- 29378538
TI  - A novel compound heterozygous variant of the SLC12A3 gene in Gitelman syndrome
      pedigree.
AB  - BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive disorder caused by
      genic mutations of SLC12A3 (Solute carrier family 12 member 3), which encodes the
      Na-Cl cotransporter (NCC), and presents with characteristic metabolic
      abnormalities, including hypokalemia, metabolic alkalosis, hypomagnesemia, and
      hypocalciuria. In this study, we report a case of a GS pedigree, including
      analysis of GS-associated gene mutations. METHODS: We performed next-generation
      sequencing analysis and Sanger sequencing to explore the SLC12A3 mutations in a
      GS pedigree that included a 35-year-old female patient with GS and five family
      members within three generations. Furthermore, we summarized their clinical
      manifestations and analyzed laboratory parameters related to GS. RESULTS: The
      female proband (the patient with GS) presented with intermittent fatigue and
      transient periods of tetany, along with significant hypokalemia, hypomagnesemia,
      and hypocalciuria. All other members of the pedigree had normal laboratory
      results without obvious GS-related symptoms. Genetic analysis of the SLC12A3 gene
      identified two novel missense mutations (c.1919A > G, p.N640S in exon 15; c.2522A
      > G, p.D841G in exon 21) in the patient with GS. Moreover, we demonstrated that
      her mother, younger maternal uncle, and cousin were carriers of one mutation
      (c.1919A > G), and her father was the carrier of the other (c.2522A > G).
      CONCLUSION: This is the first report of these two novel pathogenic variants of
      SLC12A3 and their contribution to GS. Further functional studies are particularly
      warranted to explore the underlying molecular mechanisms.

PMID- 29378536
TI  - A protocol for the HeadCoach trial: the development and evaluation of an online
      mental health training program for workplace managers.
AB  - BACKGROUND: Within high income countries, mental health is now the leading cause
      of long term sickness absence in the workplace. Managers are in a position to
      make changes and decisions that have a positive effect on the wellbeing of staff,
      the recovery of employees with mental ill health, and potentially prevent future
      mental health problems. However, managers report addressing workplace mental
      health issues as challenging. The aim of the HeadCoach trial is to evaluate the
      effectiveness of a newly developed online training intervention to determine
      whether it is able to build managers' confidence to better support individuals
      within their teams who are experiencing mental ill health, and the confidence to
      promote manager behaviour likely to result in a more mentally healthy workplace.
      METHODS/DESIGN: We will conduct a cluster randomised control trial (RCT) to
      evaluate the effect of HeadCoach, an online training intervention for managers
      with a focus on the mental health of their employees, compared to a waitlist
      control. The target sample is 168 managers, and their direct employees. Managers
      and employees will be assessed at baseline and at 4-month follow up. Managers
      will have an additional, intermediate assessment 6-weeks post-baseline. The
      primary outcome is change from baseline in managers' self-reported confidence
      when dealing with mental health issues within their team and promoting a mentally
      healthy workplace. The difference between the intervention and waitlist control
      groups will be assessed using linear mixed effects repeated measures (MMRM)
      analysis of variance (ANOVA). Secondary managerial outcomes include mental health
      literacy, attitudes towards mental health issues in the workplace and managerial
      behaviour in dealing with mental health matters with their staff. Employee
      outcomes will be perceived level of manager support, engagement, psychological
      distress, and rates of sickness absence and presenteeism. DISCUSSION: To our
      knowledge this will be the first RCT of a purely online training intervention
      developed specifically for managers that promotes confidence to both support
      staff experiencing mental ill health and create a mentally healthy work
      environment. If successful, this intervention has the potential to provide an
      effective and efficient method of training managers in workplace mental health
      and to enhance employee wellbeing. TRIAL REGISTRATION: Australian and New Zealand
      Clinical Trials Registry ACTRN12617000279325.

PMID- 29378539
TI  - Leptospirosis presenting as haemolytic uraemic syndrome: a case report.
AB  - BACKGROUND: Leptospirosis is a rare infectious disease especially in Western
      Countries. Renal involvement is a recognised complication of leptospirosis but
      leptospirosis-associated haemolytic uraemic syndrome is extremely rare and to our
      knowledge has only been reported once, in 1985. CASE PRESENTATION: A 29-year-old
      male was transferred to our Renal Unit with fevers, myalgia and diarrhoeal
      illness. Laboratory investigations revealed an acute kidney injury, acute liver
      injury, significantly raised lactate dehydrogenase with marked anaemia,
      thrombocytopenia and schistocytes on a blood film. A diagnosis of haemolytic
      uraemic syndrome was made. Surprisingly, the stool culture was negative which led
      to a suspicion of leptospirosis as one of the differential diagnoses. This was
      subsequently confirmed by enzyme-linked immunosorbent assay and microscopic
      agglutination test. He received plasma exchange and antibiotics and made a
      complete recovery on discharge. CONCLUSION: Leptospirosis presenting as
      haemolytic uraemic syndrome is rare but should be considered in the differential
      diagnosis especially in the presence of significant liver injury, as current
      evidence suggests that the disease is re-emerging.

PMID- 29378541
TI  - Measurement of sexual health outcomes among people who inject drugs: pilot study
      in Catalonia, Spain and Barnaul, Russia.
AB  - BACKGROUND: The main objective of this study was to test some of the draft sexual
      health indicators developed by the World Health Organization as part of a
      comprehensive indicator framework to monitor progress in universal access to
      reproductive health. METHODS: Cross-sectional studies among people who inject
      drugs were conducted in Catalonia (n = 734) and Barnaul (n = 500). 'Sexual
      competency' was measured using three indicators: sexual satisfaction, sexual
      safety, and sexual autonomy. Individual social norms on sexuality were also
      collected. The construct validity of the sexual safety and sexual autonomy items
      were assessed. Multivariate logistic regression models explored factors
      associated with sexual dissatisfaction. RESULTS: In Catalonia, sexual competency
      was higher among males than females who inject drugs (60.4% versus 33.3%). In
      both Catalonia and Barnaul, differences by sex in social norms on sexuality were
      seen. Mean scores on sexual safety (4.15 in Catalonia and 3.54 in Barnaul) were
      lower among participants who reported not using condoms. Mean scores on sexual
      autonomy (4.42 in Catalonia and 3.97 in Barnaul) were lower among those who had
      experienced some form of sexual assault. Perceived sexual safety, sexual
      autonomy, and social norms on sexuality were associated with sexual
      dissatisfaction. CONCLUSIONS: The sexual health indicators tested are valid,
      feasible, and reliable tools to monitor and evaluate sexual health programs and
      activities. The results confirm that sexual satisfaction depends on safe sexual
      experiences, free from coercion and violence. Social norms and individual
      perceptions about sexual health need to be considered when developing national
      disease prevention programs.

PMID- 29378540
TI  - Detecting frail, older adults and identifying their strengths: results of a mixed
      methods study.
AB  - BACKGROUND: The debate on frailty in later life focuses primarily on deficits and
      their associations with adverse (health) outcomes. In addition to deficits, it
      may also be important to consider the abilities and resources of older adults.
      This study was designed to gain insights into the lived experiences of frailty
      among older adults to determine which strengths can balance the deficits that
      affect frailty. METHODS: Data from 121 potentially frail community-dwelling older
      adults in Flemish-speaking Region of Belgium and Brussels were collected using a
      mixed-methods approach. Quantitative data were collected using the Comprehensive
      Frailty Assessment Instrument (CFAI), Montreal Cognitive Assessment (MoCA), and
      numeric rating scales (NRS) for quality of life (QoL), care and support, meaning
      in life, and mastery. Bivariate analyses, paired samples t-tests and means were
      performed. Qualitative data on experiences of frailty, frailty balance, QoL, care
      and support, meaning in life, and mastery were collected using semi-structured
      interviews. Interviews were subjected to thematic content analysis. RESULTS: The
      "no to mild frailty" group had higher QoL, care and support, meaning in life, and
      mastery scores than the "severe frailty" group. Nevertheless, qualitative results
      indicate that, despite being classified as frail, many older adults experienced
      high levels of QoL, care and support, meaning in life, and mastery. Respondents
      mentioned multiple balancing factors for frailty, comprising individual-level
      circumstances (e.g., personality traits, coping strategies, resilience),
      environmental influences (e.g., caregivers, neighborhood, social participation),
      and macro-level features (e.g., health literacy, adequate financial
      compensation). Respondents also highlighted that life changes affected their
      frailty balance, including changes in health, finances, personal relationships,
      and living situation. CONCLUSION: The findings indicate that frailty among older
      individuals can be considered as a dynamic state and, regardless of frailty,
      balancing factors are important in maintaining a good QoL. The study investigated
      not only the deficits, but also the abilities, and resources of frail, older
      adults. Public policymakers and healthcare organizations are encouraged to
      include these abilities, supplementary or even complementary to the usual focus
      on deficits.

PMID- 29378543
TI  - Smoking behavior of males attending the quit tobacco clinics in Bahrain and their
      knowledge on tobacco smoking health hazards.
AB  - BACKGROUND: One third of Bahraini adult (20-64 years) males and 7.0% of females
      use some form of tobacco. The corresponding rates for cigarette and waterpipe
      tobacco smoking (WTS) are 11.0% and 6.0%, respectively. The objective of the
      study was to determine the knowledge on tobacco smoking and past smoking related
      behavior of male patients attending the Quit Tobacco Clinics (QTC) in Bahrain.
      METHODS: A sample of 339 male clinic attendees was taken proportional to the
      population distribution in the three QTC at Al Hoora Health Center, Hamad Kanoo
      Health Center, and Bank of Bahrain and Kuwait Health Center. Data collection was
      performed until the sample size was completed (September 2015 to December 2016).
      Knowledge on the health effects of cigarette and WTS was examined based on 10
      statements on cigarette and similar ones on WTS. Respondents "agreeing" with the
      statements were considered knowledgeable and those "disagreeing" or responding
      "don't know", not knowledgeable. All the "agree" responses for cigarette/WTS were
      summed across the 10 health effects and average health knowledge scores for
      cigarette/WTS were computed. RESULTS: Most of the study participants were
      Bahraini nationals, ever married and educated with at least secondary level. The
      majority (65.8%) of participants smoked a single type of tobacco product, and the
      rest, two (28.0%) or three or more (6.2%). Age of starting cigarette and WTS was
      16.2 +/- 4.0 and 19.3 +/- 6.7 years, respectively. The majority (81%) smoked in
      the presence of other family members and 26.3% in the presence of a child. 76.2%
      smoked in the presence of others in their cars. 18.9% of the attendees had quit
      smoking at the time of interview. 81% of the participants knew about the hazards
      of both cigarette and WTS with a significantly higher (p = 0.0001) mean knowledge
      score for cigarette (93.3 +/- 3.0%) than WTS (85.2 +/- 2.1%). CONCLUSION: The
      relative lack of knowledge on the hazards of WTS in a sample of Arab country
      population with an increasing trend of WTS warrants the attention of health
      policy makers in the country and region.

PMID- 29378542
TI  - Interrupting seasonal transmission of Schistosoma haematobium and control of soil
      transmitted helminthiasis in northern and central Cote d'Ivoire: a SCORE study
      protocol.
AB  - BACKGROUND: To achieve a world free of schistosomiasis, the objective is to scale
      up control and elimination efforts in all endemic countries. Where interruption
      of transmission is considered feasible, countries are encouraged to implement a
      comprehensive intervention package, including preventive chemotherapy,
      information, education and communication (IEC), water, sanitation and hygiene
      (WASH), and snail control. In northern and central Cote d'Ivoire, transmission of
      Schistosoma haematobium is seasonal and elimination might be achieved. In a
      cluster-randomised trial, we will assess different treatment schemes to interrupt
      S. haematobium transmission and control soil-transmitted helminthiasis over a 3
      year period. We will compare the impact of (i) arm A: annual mass drug
      administration (MDA) with praziquantel and albendazole before the peak
      schistosomiasis transmission season; (ii) arm B: annual MDA after the peak
      schistosomiasis transmission season; (iii) arm C: two yearly treatments before
      and after peak schistosomiasis transmission; and (iv) arm D: annual MDA before
      peak schistosomiasis transmission, coupled with chemical snail control using
      niclosamide. METHODS/DESIGN: The prevalence and intensity of S. haematobium and
      soil-transmitted helminth infections will be assessed using urine filtration and
      Kato-Katz thick smears, respectively, in six administrative regions in northern
      and central parts of Cote d'Ivoire. Once a year, urine and stool samples will be
      collected and examined from 50 children aged 5-8 years, 100 children aged 9-12
      years and 50 adults aged 20-55 years in each of 60 selected villages. Changes in
      S. haematobium and soil-transmitted helminth prevalence and intensity will be
      assessed between years and stratified by intervention arm. In the 15 villages
      randomly assigned to intervention arm D, intermediate host snails will be
      collected three times per year, before niclosamide is applied to the selected
      freshwater bodies. The snail abundance and infection rates over time will allow
      drawing inference on the force of transmission. DISCUSSION: This cluster
      randomised intervention trial will elucidate whether in an area with seasonal
      transmission, the four different treatment schemes can interrupt S. haematobium
      transmission and control soil-transmitted helminthiasis. Lessons learned will
      help to guide schistosomiasis control and elimination programmes elsewhere in
      Africa. TRIAL REGISTRATION: ISRCTN ISRCTN10926858 . Registered 21 December 2016.
      Retrospectively registered.

PMID- 29378544
TI  - Cigarette smoking and smoking-attributable diseases among Estonian physicians: a
      cross-sectional study.
AB  - BACKGROUND: Smoking is a risk factor for several diseases. Physicians are role
      models for their patients. Physicians who smoke underestimate the health risks of
      smoking and may be less likely to offer advice to help their patients to quit.
      The aim of this study was to: provide an overview of smoking behaviour among
      Estonian physicians; assess the relationship between smoking and ischaemic heart
      disease (IHD), chronic bronchitis (CB), and lung emphysema (LE); and estimate
      fractions of prevalences of the three diseases attributable to smoking. METHODS:
      Self-administered questionnaires were sent to practising physicians (n = 5666) in
      Estonia in 2014. Prevalence of smoking and relative risks for IHD, CB and LE as
      well as the risks of IHD, CB and LE attributable to smoking were calculated by
      age and sex. Post-stratification was used to compensate non-response. RESULTS:
      There were 535 male and 2404 female physicians participating. The prevalence of
      daily smoking was 12.4% (95% CI 10.4-14.4%) among men and 5.0% (95% CI 4.4-5.6%)
      among women. Mean duration of smoking among male and female daily smokers was
      28.6 (95% CI 26.1-31.1) and 28.6 (95% CI 27.1-30.2) years. Compared to lifelong
      non-smokers, the age-adjusted risk for IHD was 1.29 times (95% CI 0.88-1.89)
      higher for men, but 1.69 times (95% CI 1.17-2.40) lower for all women who have
      ever smoked. The risk for CB was 2.29 (95% CI 1.30-4.03) times higher for smokers
      among men and, 1.32 (95% CI 0.95-1.82) among women; the risk ratio for LE was
      4.92 (95% CI 1.14-21.1) among men and 2.45 (95% CI 0.63-9.52) among women. The
      smoking-attributable risk for IHD was 3.2% (95% CI 2.3-4.1%) among men and - 0.1%
      (95% CI -0.7-0.4%) among women; for CB 6.9% (95% CI 6.0-7.8%) and 4.2% (95% CI
      3.5-4.8%); and for LE 18.8% (95% CI 17.0-22.5%) and 22.6% (95% CI 18.5-26.9%),
      respectively. CONCLUSION: Prevalence of daily smoking was relatively low among
      Estonian physicians (and twice lower among female physicians). The risk
      attributable to smoking was higher for LE and CB than for IHD.

PMID- 29378546
TI  - Identifying factors influencing contraceptive use in Bangladesh: evidence from
      BDHS 2014 data.
AB  - BACKGROUND: Birth control is the conscious control of the birth rate by methods
      which temporarily prevent conception by interfering with the normal process of
      ovulation, fertilization, and implantation. High contraceptive prevalence rate is
      always expected for controlling births for those countries that are experiencing
      high population growth rate. The factors that influence contraceptive prevalence
      are also important to know for policy implication purposes in Bangladesh. This
      study aims to explore the socio-economic, demographic and others key factors that
      influence the use of contraception in Bangladesh. METHODS: The contraception data
      are extracted from the 2014 Bangladesh Demographic and Health Survey (BDHS) data
      which were collected by using a two stage stratified random sampling technique
      that is a source of nested variability. The nested sources of variability must be
      incorporated in the model using random effects in order to model the actual
      parameter effects on contraceptive prevalence. A mixed effect logistic regression
      model has been implemented for the binary contraceptive data, where parameters
      are estimated through generalized estimating equation by assuming exchangeable
      correlation structure to explore and identify the factors that truly affect the
      use of contraception in Bangladesh. RESULTS: The prevalence of contraception use
      by currently married 15-49 years aged women or their husbands is 62.4%. Our study
      finds that administrative division, place of residence, religion, number of
      household members, woman's age, occupation, body mass index, breastfeeding
      practice, husband's education, wish for children, living status with wife, sexual
      activity in past year, women amenorrheic status, abstaining status, number of
      children born in last five years and total children ever died were significantly
      associated with contraception use in Bangladesh. CONCLUSIONS: The odds of women
      experiencing the outcome of interest are not independent due to the nested
      structure of the data. As a result, a mixed effect model is implemented for the
      binary variable 'contraceptive use' to produce true estimates for the significant
      determinants of contraceptive use in Bangladesh. Knowing such true estimates is
      important for attaining future goals including increasing contraception use from
      62 to 75% by 2020 by the Bangladesh government's Health, Population & Nutrition
      Sector Development Program (HPNSDP).

PMID- 29378545
TI  - Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for
      non-vaccination; two systematic reviews.
AB  - BACKGROUND: Despite effective national immunisation programmes in Europe, some
      groups remain incompletely or un-vaccinated ('under-vaccinated'), with
      underserved minorities and certain religious/ideological groups repeatedly being
      involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into
      factors regarding acceptance of vaccination of 'under-vaccinated groups' (UVGs)
      might give opportunities to communicate with them in a trusty and reliable manner
      that respects their belief system and that, maybe, increase vaccination uptake.
      We aimed to identify and describe UVGs in Europe and to describe beliefs,
      attitudes and reasons for non-vaccination in the identified UVGs. METHODS: We
      defined a UVG as a group of persons who share the same beliefs and/or live in
      socially close-knit communities in Europe and who have/had historically low
      vaccination coverage and/or experienced outbreaks of VPDs since 1950. We searched
      MEDLINE, EMBASE and PsycINFO databases using specific search term combinations.
      For the first systematic review, studies that described a group in Europe with an
      outbreak or low vaccination coverage for a VPD were selected and for the second
      systematic review, studies that described possible factors that are associated
      with non-vaccination in these groups were selected. RESULTS: We selected 48
      articles out of 606 and 13 articles out of 406 from the first and second search,
      respectively. Five UVGs were identified in the literature: Orthodox Protestant
      communities, Anthroposophists, Roma, Irish Travellers, and Orthodox Jewish
      communities. The main reported factors regarding vaccination were perceived non
      severity of traditional "childhood" diseases, fear of vaccine side-effects, and
      need for more information about for example risk of vaccination. CONCLUSIONS:
      Within each UVG identified, there are a variety of health beliefs and objections
      to vaccination. In addition, similar factors are shared by several of these
      groups. Communication strategies regarding these similar factors such as
      educating people about the risks associated with being vaccinated versus not
      being vaccinated, addressing their concerns, and countering vaccination myths
      present among members of a specific UVG through a trusted source, can establish a
      reliable relationship with these groups and increase their vaccination uptake.
      Furthermore, other interventions such as improving access to health care could
      certainly increase vaccination uptake in Roma and Irish travellers.

PMID- 29378547
TI  - The Research and Evaluation of Antipsychotic Treatment in Community Behavioral
      Health Organizations, Outcomes (REACH-OUT) study: real-world clinical practice in
      schizophrenia.
AB  - BACKGROUND: Outpatient facilities, such as community behavioral health
      organizations (CBHOs), play a critical role in the care of patients with serious
      mental illness, but there is a paucity of "real-world" patient outcomes data from
      this health care setting. Therefore, we conducted The Research and Evaluation of
      Antipsychotic Treatment in Community Behavioral Health Organizations, Outcomes
      (REACH-OUT) trial, a real-world, prospective, noninterventional observational
      study of patients with mental illness treated at CBHOs across the United States.
      We describe demographic and clinical characteristics, antipsychotic therapy (APT)
      treatment patterns, and health care resource utilization in patients with
      schizophrenia undergoing medical care as usual. METHODS: This study enrolled
      adults with schizophrenia or bipolar I disorder who initiated APT treatment at
      various time points: 1) within 8 weeks of initiating risperidone long-acting
      injectables (RLAIs) or other APTs except paliperidone palmitate (PP), 2) after
      more than 24 weeks of continuous RLAI treatment, or 3) at any time after
      initiating PP LAI treatment (schizophrenia only). Study assessments were
      performed via participant interview, medical chart abstraction, and clinical
      survey at enrollment and at month 12. RESULTS: A total of 1065 patients from 46
      CBHOs were enrolled. Of these, 944 (88.6%) had a diagnosis of schizophrenia and
      121 (11.4%) had bipolar I disorder. At enrollment, 599 (63.5%) of patients with
      schizophrenia were receiving RLAIs or PP LAI, 281 (29.8%) were receiving oral
      APTs, and 64 (6.8%) were receiving other injectable APTs. A number of differences
      in patient characteristics and outcomes were observed between patients in the LAI
      APT cohort and the oral APT cohort. CONCLUSION: Descriptive analyses from this
      observational study suggest differences in the patient characteristics, treatment
      patterns, and clinical and economic outcomes among those with schizophrenia
      treated at CBHOs with LAI APT or oral APTs. Additional analyses will be conducted
      to delineate the impact of LAI APT versus oral APTs on patient outcomes. TRIAL
      REGISTRATION: Clinical Trial Registry: NCT01181960 . Registered 12 August 2010.

PMID- 29378548
TI  - "I beg you...breastfeed the baby, things changed": infant feeding experiences
      among Ugandan mothers living with HIV in the context of evolving guidelines to
      prevent postnatal transmission.
AB  - BACKGROUND: For women living with HIV (WLWH) in low- and middle-income countries,
      World Health Organization (WHO) infant feeding guidelines now recommend exclusive
      breastfeeding until six months followed by mixed feeding until 24 months,
      alongside lifelong maternal antiretroviral therapy (ART). These recommendations
      represent the sixth major revision to WHO infant feeding guidelines since 1992.
      We explored how WLWH in rural Uganda make infant feeding decisions in light of
      evolving recommendations. METHODS: We conducted semi-structured interviews with
      20 postpartum Ugandan WLWH accessing ART, who reported pregnancy < 2 years prior
      to recruitment. Interviews were conducted between February-August 2014 with
      babies born between March 2012-October 2013, over which time, the regional HIV
      treatment clinic recommended lifelong ART for all pregnant and breastfeeding
      women (Option B+). Content analysis was used to identify major themes. Infant
      feeding experiences was an emergent theme. NVivo 10 software was used to organize
      analyses. RESULTS: Among 20 women, median age was 33 years [IQR: 28-35], number
      of livebirths was 3 [IQR: 2-5], years on ART was 2.3 [IQR: 1.5-5.1], and 95% were
      virally suppressed. Data revealed that women valued opportunities to reduce
      postnatal transmission. However, women made infant feeding choices that differed
      from recommendations due to: (1) perception of conflicting recommendations
      regarding infant feeding; (2) fear of prolonged infant HIV exposure through
      breastfeeding; and (3) social and structural constraints shaping infant feeding
      decision-making. CONCLUSIONS: WLWH face layered challenges navigating evolving
      infant feeding recommendations. Further research is needed to examine guidance
      and decision-making on infant feeding choices to improve postpartum experiences
      and outcomes. Improved communication about changes to recommendations is needed
      for WLWH, their partners, community members, and healthcare providers.

PMID- 29378549
TI  - Anti-apoptotic potential of several antidiabetic medicinal plants of the eastern
      James Bay Cree pharmacopeia in cultured kidney cells.
AB  - BACKGROUND: Our team has identified 17 Boreal forest species from the traditional
      pharmacopeia of the Eastern James Bay Cree that presented promising in vitro and
      in vivo biological activities in the context of type 2 diabetes (T2D). We now
      screened the 17 plants extracts for potential anti-apoptotic activity in cultured
      kidney cells and investigated the underlying mechanisms. METHODS: MDCK (Madin
      Darnby Canine Kidney) cell damage was induced by hypertonic medium (700 mOsm/L)
      in the presence or absence of maximal nontoxic concentrations of each of the 17
      plant extracts. After 18 h' treatment, cells were stained with Annexin V (AnnV)
      and Propidium iodide (PI) and subjected to flow cytometry to assess the
      cytoprotective (AnnV-/PI-) and anti-apoptotic (AnnV+/PI-) potential of the 17
      plant extracts. We then selected a representative subset of species (most
      cytoprotective, moderately so or neutral) to measure the activity of caspases 3,
      8 and 9. RESULTS: Gaultheria hispidula and Abies balsamea are amongst the most
      powerful cytoprotective and anti-apoptotic plants and appear to exert their
      modulatory effect primarily by inhibiting caspase 9 in the mitochondrial
      apoptotic signaling pathway. CONCLUSION: We conclude that several Cree
      antidiabetic plants exert anti-apoptotic activity that may be relevant in the
      context of diabetic nephropathy (DN) that affects a significant proportion of
      Cree diabetics.

PMID- 29378550
TI  - Tools for a systematic appraisal of integrated community-based approaches to
      prevent childhood obesity.
AB  - BACKGROUND: Evaluation and monitoring methods are often unable to identify
      crucial elements of success or failure of integrated community-wide approaches
      aiming to tackle childhood overweight and obesity, yet difficult to determine in
      complex programmes. Therefore, we aimed to systematically appraise strengths and
      weaknesses of such programmes and to assess the usefulness of the appraisal tools
      used. METHODS: To identify strengths and weaknesses of the integrated community
      based approaches two tools were used: the Good Practice Appraisal tool for
      obesity prevention programmes, projects, initiatives and intervention (GPAT), a
      self-administered questionnaire developed by the WHO; and the OPEN tool, a
      structured list of questions based on the EPODE theory, to assist face-to-face
      interviews with the principle programme coordinators. The strengths and
      weaknesses of these tools were assessed with regard to practicalities, quality of
      acquired data and the appraisal process, criteria and scoring. RESULTS: Several
      strengths and weaknesses were identified in all the assessed integrated community
      based approaches, different for each of them. The GPAT provided information
      mostly on intervention elements whereas through the OPEN tool information on both
      the programme and intervention levels were acquired. CONCLUSION: Large
      variability between integrated community-wide approaches preventing childhood
      obesity in the European region was identified and therefore each of them has
      different needs. Both tools used in combination seem to facilitate comprehensive
      assessment of integrated community-wide approaches in a systematic manner, which
      is rarely conducted. Nonetheless, the tools should be improved in line to their
      limitations as recommended in this manuscript.

PMID- 29378551
TI  - Stimulatory effect of icariin on the proliferation of neural stem cells from rat
      hippocampus.
AB  - BACKGROUND: Icariin (ICA), a major ingredient of Epimediumbrevicornum, has
      various pharmacological activities including central nervous system protective
      functions such as the improvement of learning and memory function in mice models
      of Alzheimer's disease. It has been reported that ICA can promote regeneration of
      peripheral nerve and functional recovery. The purpose of this study was to
      investigate the potentiating effect of ICA on the proliferation of rat
      hippocampal neural stem cells, and explore the possible mechanism involved.
      METHODS: Primary neural stem cells were prepared from the hippocampus of newly
      born SD rats, and cells were cultured in special stem cell culture medium. Neural
      stem cells were confirmed by immunofluorescence detection of nestin, NSE and GFAP
      expression. The effect of ICA on the growth and proliferation of the neural stem
      cells was evaluated by 5-ethynyl-2-deoxyuridine (EdU) labeling of proliferating
      cells, and photomicrographic images of the cultured neural stem cells. Further,
      the mechanism of ICA-induced cell proliferation of neural stem cells was
      investigated by analyzing the gene and protein expression of cell cycle related
      genes cyclin D1 and p21. RESULTS: The present study showed that icariin promotes
      the growth and proliferation of neural stem cells from rat hippocampus in a dose
      dependent manner. Incubation of cells with icariin resulted in significant
      increase in the number of stem cell spheres as well as the increased
      incorporation of EdU when compared with cells exposed to control vehicle. In
      addition, it was found that icariin-induced effect on neural stem cells is
      associated with increased mRNA and protein expression of cell cycle genes cyclin
      D1 and p21. CONCLUSIONS: This study evidently demonstrates the potentiating
      effect of ICA on neural stem cell growth and proliferation, which might be
      mediated through regulation of cell cycle gene and protein expression promoting
      cell cycle progression.

PMID- 29378552
TI  - Optimized DNA electroporation for primary human T cell engineering.
AB  - BACKGROUND: Effective gene-delivery systems for primary human T cell engineering
      are useful tools for both basic research and clinical immunotherapy applications.
      Pseudovirus-based systems and electro-transfection are the most popular
      strategies for genetic material transduction. Compared with viral-particle
      mediated approaches, electro-transfection is theoretically safer, because it does
      not promote transgene integration into the host genome. Additionally, the
      simplicity and speed of the procedure increases the attractiveness of
      electroporation. Here, we developed and optimized an electro-transfection method
      for the production of engineered chimeric antigen receptor (CAR)-T cells.
      RESULTS: Stimulation of T cells had the greatest effect on their transfection,
      with stimulation of cells for up to 3 days substantially improving transfection
      efficiency. Additionally, the strength of the external electric field, input cell
      number, and the initial amount of DNA significantly affected transfection
      performance. The voltage applied during electroporation affected plasmid
      permeation and was negatively correlated with the number of viable cells after
      electroporation. Moreover, higher plasmid concentration increased the proportion
      of positively transfected cells, but decreased cell viability, and for single
      activated cells, higher cell density enhanced their viability. We evaluated the
      effects of two clinically relevant factors, serum supplementation in the culture
      medium and cryopreservation immediately after the isolation of peripheral blood
      lymphocytes. Our findings showed that our protocol performed well using xeno-free
      cultured, fresh T cells, with application resulting in a lower but acceptable
      transfection efficiency of cells cultured with fetal bovine serum or thawed
      cells. Furthermore, we described an optimized procedure to generate CAR-T cells
      within 6 days and that exhibited cytotoxicity toward targeted cells. CONCLUSIONS:
      Our investigation of DNA electro-transfection for the use in human primary T cell
      engineering established and validated an optimized method for the construction of
      functional CAR-T cells.

PMID- 29378553
TI  - Improving public health evaluation: a qualitative investigation of practitioners'
      needs.
AB  - BACKGROUND: In 2011, the House of Lords published a report on Behaviour Change,
      in which they report that "a lot more could, and should, be done to improve the
      evaluation of interventions." This study aimed to undertake a needs assessment of
      what kind of evaluation training and materials would be of most use to UK public
      health practitioners by conducting interviews with practitioners about everyday
      evaluation practice and needed guidance and materials. METHODS: Semi-structured
      interviews were conducted with 32 public health practitioners in two UK regions,
      Cambridgeshire and the South West. Participants included directors of public
      health, consultants in public health, health improvement advisors, public health
      intelligence, and public health research officers. A topic guide included
      questions designed to explore participants existing evaluation practice and their
      needs for further training and guidance. Data were analysed using thematic
      analyses. RESULTS: Practitioners highlighted the need for evaluation to defend
      the effectiveness of existing programs and protect funding provisions. However,
      practitioners often lacked training in evaluation, and felt unqualified to
      perform such a task. The majority of practitioners did not use, or were not aware
      of many existing evaluation guidance documents. They wanted quality-assured,
      practical guidance that relate to the real world settings in which they operate.
      Practitioners also mentioned the need for better links and support from academics
      in public health. CONCLUSION: Whilst numerous guidance documents supporting
      public health evaluation exist, these documents are currently underused by
      practitioners - either because they are not considered useful, or because
      practitioners are not aware of them. Integrating existing guides into a catalogue
      of guidance documents, and developing a new-quality assured, practical and useful
      document may support the evaluation of public health programs. This in turn has
      the potential to identify those programs that are effective; thus improving
      public health and reducing financial waste.

PMID- 29378554
TI  - Screening of Baccaurea ramiflora (Lour.) extracts for cytotoxic, analgesic, anti
      inflammatory, neuropharmacological and antidiarrheal activities.
AB  - BACKGROUND: It has been observed that the various part of Baccaurea ramiflora
      plant is used in rheumatoid arthritis, cellulitis, abscesses, constipation and
      injuries. This plant also has anticholinergic, hypolipidemic, hypoglycemic,
      antiviral, antioxidant, diuretic and cytotoxic activities. The present studyaimed
      to assess the cytotoxic, analgesic, anti-inflammatory, CNS depressant and
      antidiarrheal activities of methanol extract of Baccaurea ramiflora pulp and
      seeds in mice model. METHODS: The cytotoxic activity was determined by brine
      shrimp lethality bioassay; anti-nociceptive activity was determined by acetic
      acid-induced writhing, formalin- induced licking and biting, and tail immersion
      methods. The anti-inflammatory, CNS depressant and anti-diarrheal activities were
      assessed by carrageenan-induced hind paw edema, the open field and hole cross
      tests, and castor oil-induced diarrheal methods, respectively. The data were
      analyzed by one way ANOVA (analysis of variance) followed by Dunnett's test.
      RESULTS: In brine shrimp lethality bioassay, the LC50 values of the methanol
      extracts of Baccaurea ramiflora pulp and seed were 40 MUg/mL and 10 MUg/mL,
      respectively. Our investigation showed that Baccaurea ramiflora pulp and seed
      extracts (200 mg/kg) inhibited acetic acid induced pain 67.51 and 66.08%,
      respectively (p < 0.05) that was strongly comparable with that of Ibuprofen (72%)
      (p < 0.05). The Baccaurea ramiflora pulp and seed extracts (200 mg/kg)
      significantly (p < 0.05) reduced 58.5 and 53.4 in early and 80.8%, 76.61% in late
      phase of formalin-induced licking and biting. At 60 and 90 min pulp and seed
      extracts (200 mg/kg) inhibited nociception of thermal stimulus 50.16 and 62.4%,
      respectively (p < 0.05) which was comparable with the standard (morphine, 75.9%
      inhibition). The pulp and seed extracts (200 mg/kg) significantly (p < 0.05)
      reduced inflammation (42.00 and 55.22%, respectively) in carrageenan-induced hind
      paw edema and defecations (59.7 and 63.03%, respectively) in castor oil induced
      diarrhea. Both the extracts showed high sedative activity at 30, 60, 90, and 120
      min. CONCLUSION: Our investigation demonstrated significant cytotoxic, analgesic,
      anti-inflammatory, CNS depressant and antidiarrheal activities of methanol
      extract of Baccaurea ramiflora pulp and seeds (200 mg/kg).

PMID- 29378555
TI  - The clinical course and pathophysiological investigation of adolescent
      gestational diabetes insipidus: a case report.
AB  - BACKGROUND: Gestational diabetes insipidus (GDI) is a rare endocrine complication
      during pregnancy that is associated with vasopressinase overproduction from the
      placenta. Although increased vasopressinase is associated with placental volume,
      the regulation of placental growth in the later stage of pregnancy is not well
      known. CASE PRESENTATION: A 16-year-old pregnant woman was urgently transferred
      to our hospital because of threatened premature labor when the Kumamoto
      earthquakes hit the area where she lived. During her hospitalization, she
      complained of gradually increasing symptoms of polyuria and polydipsia. The serum
      level of arginine vasopressin (AVP) was 1.7 pg/mL, which is inconsistent with
      central DI. The challenge of diagnostic treatment using oral 1-deamino-8-D-AVP
      (DDAVP) successfully controlled her urine and allowed for normal delivery. DDAVP
      tablets were not necessary to control her polyuria thereafter. Based on these
      observations, clinical diagnosis of GDI was confirmed. Pathophysiological
      analyses revealed that vasopressinase expression was more abundant in the GDI
      patient's syncytiotrophoblast in placenta compared with that in a control
      subject. Serum vasopressinase was also observed during gestation and disappeared
      soon after delivery. Vasopressinase is reportedly identical to oxytocinase or
      insulin regulated aminopeptidase (IRAP), which is an abundant cargo protein
      associated with the glucose transporter 4 (GLUT4) storage vesicle. Interestingly,
      the expression and subcellular localization of GLUT4 appeared to occur in a
      vasopressinase (IRAP)-dependent manner. CONCLUSION: Because placental volume may
      be associated with vasopressinase overproduction in GDI, vasopressinase
      (IRAP)/GLUT4 association appears to contribute to the growth of placenta in this
      case.

PMID- 29378556
TI  - Risk factors of stunting among children living in an urban slum of Bangladesh:
      findings of a prospective cohort study.
AB  - BACKGROUND: Bangladesh is one of the 20 countries with highest burden of stunting
      globally. A large portion (around 2.2 million) of the population dwells in the
      slum areas under severe vulnerable conditions. Children residing in the slums are
      disproportionately affected with higher burden of undernutrition particularly
      stunting. In this paper, findings of a prospective cohort study which is part of
      a larger multi-country study are presented. METHODS: Two hundred and sixty five
      children were enrolled and followed since their birth till 24 months of age.
      Anthropometric measurements, dietary intake and morbidity information were
      collected monthly. Data from 9 to 12, 15-18 and 21-24 months were collated to
      analyze and report findings for 12, 18 and 24 months of age. Generalized
      estimating equation models were constructed to determine risk factors of stunting
      between 12 and 24 months of age. RESULT: Approximately, 18% of children were
      already stunted (LAZ < -2SD) at birth and the proportion increased to 48% at 24
      months of age. Exclusive breastfeeding prevalence was only 9.4% following the WHO
      definition at 6 months. Dietary energy intake as well as intakes of carbohydrate,
      fat and protein were suboptimal for majority of the children. However, in
      regression analysis, LAZ at birth (AOR = 0.40, 95% CI: 0.26, 0.61), household
      with poor asset index (AOR = 2.81, 95% CI: 1.43, 5.52; ref.: average asset
      index), being male children (AOR = 1.75, 95% CI: 1.04, 2.95; ref.: female) and
      age (AOR = 2.34, 95% CI: 1.56, 3.52 at 24 months, AOR = 2.13, 95% CI: 1.55, 2.92
      at 18 months; ref.: 12 months of age) were the significant predictors of stunting
      among this population. CONCLUSION: As the mechanism of stunting begins even
      before a child is born, strategies must be focused on life course approach and
      preventive measurement should be initiated during pregnancy. Alongside,
      government and policymakers have to develop sustainable strategies to improve
      various social and environmental factors those are closely interrelated with
      chronic undernutrition particularly concentrating on urban slum areas.

PMID- 29378557
TI  - Determinants of excellent/good self-rated health among HIV positive individuals
      in South Africa: evidence from a 2012 nationally representative household survey.
AB  - BACKGROUND: In South Africa, HIV is increasingly becoming a chronic disease as a
      result of advances in HIV treatment and prevention in the last three decades.
      This has changed the perception from a life threating to a potentially manageable
      disease. However, little is known about self-perceived health status of HIV
      infected individuals. Self-rated health (SRH) has been shown to be a sensitive
      indicator of health-relatedchanges directly linked to HIV, but can also be
      influenced by differences in social and material conditions. The aim of this
      paper was to identify determinants of excellent/good SRH among HIV-infected
      individuals using socio-demographic, life style and health related data. METHODS:
      The study used data from the nationally representative 2012 South African
      population-based household survey on HIV prevalence, incidence and behaviour
      conducted using multi-stage stratified cluster sampling design. Bivariate and
      multivariate logistic regression models were used to identify determinants of SRH
      among HIV-infected individuals. RESULTS: Out of a total of 2632 HIV positive
      participants 74.1% (95% CI: 68.4-74.2) reported excellent/good SRH. Increased
      likelihood of reporting excellent/good SRH was significantly associated with
      being Black African [OR= 1.97 (95%CI: 1.12-3.46), p = 0.019] and belonging to
      least poor household [OR= 3.13 (95%CI: 1.26-7.78), p = 0.014]. Decreased
      likelihood of reporting excellent/good SRH was significantly associated with
      those aged 25 to 34 years [OR= 0.49 (95% CI: 0.31-0.78), p = 0.003], 35 to 44
      years[OR= 0.27 (95% CI: 0.17-0.44), p < 0.001], 45 to 54 years [OR= 0.20 (95% CI:
      0.12-0.34), p < 0.001], and those 55 years and older [OR= 0.15 (95% CI: 0.09
      0.26), p < 0.001], hospitalization in the past twelve months [OR= 0.40 (95% CI:
      0.26-0.60), p < 0.001]. CONCLUSION: To have positive health effects and improve
      the perceived health status for PLWH social interventions should seek to enhance
      to support for the elderly HIV-positive individuals, and address the challenge of
      socio-economic inequalities and underlying comorbid conditions resulting in
      hospitalization.

PMID- 29378558
TI  - Cytotoxicity of seputhecarpan D, thonningiol and 12 other phytochemicals from
      African flora towards human carcinoma cells.
AB  - BACKGROUND: Despite the remarkable progress in cancer therapy in recent years,
      this disease still remains a serious public health concern. The use of natural
      products has been and continues to be one of the most effective ways to fight
      malignancies. The cytotoxicity of 14 compounds from African medicinal plants was
      evaluated in four human carcinoma cell lines and normal fibroblasts. The tested
      samples included: beta-spinasterol (1), friedelanone (2), 16beta-hydroxylupeol
      (3), beta-amyrin acetate (4), lupeol acetate (5), sequoyitol (6), rhamnitrin (7),
      europetin 3-O-rhamnoside (8), thonningiol (9), glyasperin F (10), seputhecarpan B
      (11), seputhecarpan C (12), seputhecarpan D (13) and rheediaxanthone A (14).
      METHODS: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity
      of samples; caspase-Glo assay, flow cytometry for cell cycle analysis and
      mitochondrial membrane potential (MMP) as well as spectrophotometry to measure
      levels of reactive oxygen species (ROS) were performed to detect the mode of
      action of compounds 9 and 13 in MCF-7 breast adenocarcinoma cells. RESULTS:
      Compounds 3, 9-13 displayed cytotoxic effects against the four tested cancer cell
      lines with IC50 values below 85 MUM. Compounds 9 and 13 had IC50 values below 10
      MUM in 4/4 and 3/4 tested cell lines respectively. The IC50 values varied from
      0.36 MUM (against MCF7 cells) to 5.65 MUM (towards colon carcinoma DLD-1 cells)
      for 9, from 9.78 MUM (against MCF7 cells) to 67.68 MUM (against HepG2 cells) for
      13 and 0.18 MUM (towards HepG2 cells) to 72 MUM (towards Caco-2 cells) for the
      reference drug, doxorubicin. Compounds 9 and 13 induced cell cycle arrest in
      Go/G1 whilst doxorubicin induced arrest in G2/M. The two molecules (9 and 13)
      also induced apoptosis in MCF-7 cells through activation of caspases 3/7 and 9 as
      well as enhanced ROS production. CONCLUSION: Compounds 9 and 13 are good
      cytotoxic phytochemicals that should be explored more in future to develop a
      cytotoxic drug to fight human carcinoma.

PMID- 29378559
TI  - Coping strategies, vision-related quality of life, and emotional health in
      managing retinitis pigmentosa: a survey study.
AB  - BACKGROUND: Retinitis pigmentosa is a group of genetic progressive retinal
      dystrophies that may adversely affect daily life. Those with RP should develop
      adaptive coping strategies to manage their condition. This study investigates the
      relationship between engaging (ECS) and disengaging coping strategies (DCS),
      vision-related quality of life (VRQoL), and emotional health, in adults living at
      home with retinitis pigmentosa. METHOD: One hundred and five participants (70
      female; meanage of 46.98, SD age  = 13.77) completed a cross-sectional survey.
      The questionnaire booklet consisted of the Coping Strategies Inventory - Short
      Form (32 items), the National Eye Institute Visual Functioning Questionnaire 25
      (25 items), Marylands Trait Depression Scale (18 items), the Warwick-Edinburgh
      Mental Well-being Scale (14 items), and the Subjective Happiness Scale (4 items).
      RESULTS: Data was analysed with a two-block hierarchical multiple regression,
      with the first block controlling for the demographic data (age, sex, years since
      retinitis pigmentosa diagnosis, number of comorbidities, participant-perceived
      retinitis pigmentosa severity, and knowing RP type) and the second block
      consisting of primary measures (type of coping strategy, VRQoL, and Emotional
      Health). Type of coping strategy was found to impact psychosocial variables of
      VRQoL, not overall VRQoL. These psychosocial VRQoL variables had a positive
      association with ECS and a negative association with DCS. Emotional Health
      increased with ECS and decreased with DCS. There was a larger impact of DCS on
      VRQoL and Emotional Health compared to ECS, that is, VRQoL and Emotional Health
      decreased more with increasing DCS than VRQoL, and Emotional Health increased
      with increasing ECS. CONCLUSION: In concordance with previous research, ECS
      increased with increasing VRQoL and DCS decreased with increasing VRQoL. However,
      the findings also indicated that DCS had a greater impact than ECS on VRQoL and
      Emotional Health. This suggests that diminishing DCS should be prioritised over
      developing ECS to positively influence VRQoL and Emotional Health. Further
      research should investigate the impact of reducing DCS compared to increasing
      ECS, and how this may influence VRQoL and Emotional Health.

PMID- 29378560
TI  - Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via
      Activin/Follistatin regulation.
AB  - BACKGROUND: Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional
      Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However,
      elucidating the related molecular biological mechanism of how the SJHY Formula
      affects excessive inflammation in the process of re-epithelialization of diabetic
      wound healing is a task urgently needed to be fulfilled. The objectives of this
      study is to evaluate the effect of antagonisic expression of pro-/anti
      inflammatory factors on transforming growth factor-beta(TGF-beta) superfamily
      (activin and follistatin) in the process of re-epithelialization of diabetic
      wound healing in vivo, and to characterize the involvement of the
      activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and
      Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of
      SJHY formula. METHODS: SJHY Formula was prepared by pharmaceutical preparation
      room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine.
      Diabetic wound healing activity was evaluated by circular excision wound models.
      Wound healing activity was examined by macroscopic evaluation.
      Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB
      p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot,
      immunohistochemistry and hematoxylin and eosin (H&E) staining. RESULTS:
      Macroscopic evaluation analysis showed that wound healing of diabetic mice was
      delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real
      Time PCR analysis showed higher mRNA expression of activin/follistatin in
      diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay
      analysis showed reduction of activin/follistatin proteins levels by SJHY Formula
      treatment 15 days after injury. Immunohistochemistry investigated the reduction
      of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus
      diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY
      Formula accelerated re-epithelialization of diabetic wound healing. CONCLUSION:
      The present study found that diabetic delayed wound healing time is closely
      related to the high expression level of activin/follistatin, which leads to
      excessive inflammation in the process of re-epithelization. SJHY Formula
      accelerates re-epithelialization and healing time of diabetic wounds through
      decreasing the high expression of activin/follistatin.

PMID- 29378561
TI  - Primary palliative Care in General Practice - study protocol of a three-stage
      mixed-methods organizational health services research study.
AB  - BACKGROUND: The focus of this project is on improving the provision of primary
      palliative care (PC) by general practitioners (GPs). While approximately 10-15%
      of the incurable, seriously ill or dying people will be in need of specialist PC,
      the vast majority can be adequately treated within generalist care. The
      strengthening of the GP's role in PC, as well as ensuring close collaboration
      between specialist PC services and GPs have been identified as top priorities for
      the improvement of PC in Germany. Despite healthcare policy actions, diverse
      obstacles still exist to successful implementation of primary PC on a structural,
      process, and economic level. Therefore, this project aims at addressing barriers
      and facilitators to primary PC delivery in general practice in Germany. METHODS:
      The study follows a three-step approach; first, it aims at systematically
      analyzing barriers and facilitators to primary PC provision by GPs. Second, based
      on these outcomes, a tailored intervention package will be developed to enhance
      the provision of primary PC by GPs. Third, the intervention package will be
      implemented and evaluated in practice. The expected outcome will be an evidence
      based model for successful implementation of primary PC delivery tailored to the
      German healthcare system, followed by a strategic action plan on how to improve
      current practice both on a local level and nationally. DISCUSSION: The first step
      of the project has been partly completed at the time of writing. The chosen
      methodologies of four sub-projects within this first step have opened up
      different advantages and disadvantages for the data collection. In sum of all sub
      projects, the different methodologies and target groups contributed valuable
      information to the systematic analysis of barriers and facilitators to primary PC
      provision by GPs. TRIAL REGISTRATION: The study (BMBF-FK 01 GY 1610) was
      retrospectively registered at the German Clinical Trials Register (Deutsches
      Register Klinischer Studien) (Registration N degrees  DRKS00011821 ; date of
      registration: December 04th 2017) and at the German Register of health care
      research (Versorgungsforschung Deutschland - Datenbank) (Registration N degrees 
      VfD_ALLPRAX_16_003817 ; date of registration: March 30th 2017).

PMID- 29378562
TI  - Perception of inpatients following remission of a manic episode in bipolar I
      disorder on a group-based Psychoeducation program: a qualitative study.
AB  - BACKGROUND: This forms the first study of a group-based psychoeducation program
      for inpatients following remission of a manic episode in patients suffering from
      bipolar I disorder in a Chinese population. The aim was to explore the patient's
      perspectives of the program and their suggestions regarding ways to improve the
      intervention in the future. METHODS: Semi-structured and in-depth interviews were
      conducted with 15 participants who had participated in 8 sessions of a group
      psychoeducation program over 2 weeks. The verbatim transcripts of those
      interviews were analysed using thematic analysis. RESULTS: Five themes emerged
      from the data, including the patients' perception of participating in the
      program, their perception of the setting, perception of participating in a group
      program, perception of the learning content and of the outcome of participating
      in the program. CONCLUSIONS: The results presented here describe how the short
      term group psychoeducation program was experienced by the patients.
      Recommendations are also offered to improve the setting, content, and delivery.
      Our findings provide evidence that the program is beneficial for manic patients
      with bipolar I disorder, and this intervention warrants further research
      especially in a Chinese population. If these benefits are confirmed in future
      studies, this program could be incorporated into routine psychiatric inpatient
      care in China.

PMID- 29378563
TI  - Health-related physical fitness and physical activity in elementary school
      students.
AB  - BACKGROUND: This study examined associations between students' physical fitness
      and physical activity (PA), as well as what specific physical fitness components
      were more significant correlates to being physically active in different settings
      for boys and girls. METHODS: A total of 265 fifth-grade students with an average
      age of 11 voluntarily participated in this study. The students' physical fitness
      was assessed using four FitnessGram tests, including Progressive Aerobic
      Cardiovascular Endurance Run (PACER), curl-up, push-up, and trunk lift tests. The
      students' daily PA was assessed in various settings using a daily PA log for 7
      days. Data was analyzed with descriptive statistics, univariate analyses, and
      multiple R-squared liner regression methods. RESULTS: Performance on the four
      physical fitness tests was significantly associated with the PA minutes spent in
      physical education (PE) class and recess for the total sample and for girls, but
      not for boys. Performance on the four fitness tests was significantly linked to
      participation in sports/dances outside school and the total weekly PA minutes for
      the total sample, boys, and girls. Further, boys and girls who were the most
      physically fit spent significantly more time engaging in sports/dances and had
      greater total weekly PA than boys and girls who were not physically fit. In
      addition, the physically fit girls were more physically active in recess than
      girls who were not physically fit. CONCLUSIONS: Overall, students' performance on
      the four physical fitness tests was significantly associated with them being
      physically active during PE and in recess and engaging in sports/dances, as well
      as with their total weekly PA minutes, but not with their participation in non
      organized physical play outside school. TRIAL REGISTRATION: ClinicalTrials.gov
      ID: NCT03015337 , registered date: 1/09/2017, as "retrospectively registered".

PMID- 29378564
TI  - "Ways and channels for voice regarding perceptions of maternal health care
      services within the communities of the Makamba and Kayanza provinces in the
      Republic of Burundi: an exploratory study".
AB  - BACKGROUND: Increased availability of maternal health services alone does not
      lead to better outcomes for maternal health.The services need to be utilized
      first.One way to increase service utilization is to plan responsive health care
      services by taking into account the community's views or expressed needs. Burundi
      has a high maternal mortality ratio, and despite improvements in health
      infrastructure, skilled staff and the abolition of user fees for pregnant
      women,utilization of maternal health services remains low. Possible reasons for
      this include a lack of responsive healthcare services. An exploratory study was
      conducted in 2013 in two provinces of Burundi (Makamba and Kayanza), with the aim
      to collect the experiences of women and men with the maternal health
      services,their views regarding those services, channels used to express these
      experiences, and the providers' reaction. METHODS: Semi-structured interviews
      were used to collect data from men and women and key informants, including
      community health workers, health committee members, health providers, local
      authorities, religious leaders and managers of non-governmental organizations.
      Data analysis was facilitated by MAXQDA 11 software. RESULTS: Negative
      experiences with maternal health services were reported and included poor staff
      behavior towards women and a lack of medicine. Health committees and suggestion
      boxes were introduced by the government to channel the community's views.
      However, they are not used by the community members, who prefer to use community
      health workers as intermediaries. Fear of expressing oneself linked to the post
      war context of Burundi, social and gender norms, and religious norms limit the
      expression of community members' views, especially those of women. The limited
      appreciation of community health workers by the providers further hampers
      communication and acceptance of the community's views by health providers.
      CONCLUSION: In Burundi, the community voice to express views on maternal health
      services is encountering obstacles and needs to be strengthened,especially the
      women's voice. Community mobilization in the form of a mass immunization campaign
      day organized by women fora, and community empowerment using participatory
      approaches could contribute towards community voice strengthening.

PMID- 29378565
TI  - Comparison of the efficacy of nafcillin and glycopeptides as definitive therapy
      for patients with methicillin-susceptible Staphylococcus aureus bacteremia: a
      retrospective cohort study.
AB  - BACKGROUND: Studies have shown that the prognosis of the treatment of methicillin
      susceptible S. aureus (MSSA) with glycopeptides is inferior compared to treatment
      with beta-lactam. However, there are only few studies comparing treatment with
      antistaphylococcal penicillin alone to glycopeptide treatment. The aim of this
      study was to compare the efficacy of nafcillin, an antistaphylococcal penicillin,
      with that of glycopeptides as a definitive therapy for MSSA bacteremia. METHODS:
      Patients with MSSA bacteremia recruited from a tertiary referral hospital were
      enrolled in this retrospective cohort study. Demographic characteristics,
      laboratory data, and clinical outcome of the treatment were compared between a
      group receiving nafcillin and a group receiving glycopeptides. RESULTS: A total
      of 188 patients with MSSA bacteremia were included in this study. The
      glycopeptide group had a higher rate of malignancy (28.6 vs. 60.8%, p < 0.001)
      and proportion of healthcare-associated infections (47.3 vs. 72.2%, p < 0.001)
      compared to the nafcillin group. The ratio of skin and soft tissue infections
      (30.0 vs. 16.7%, p = 0.037) and bone and joint infections (17.8 vs. 6.3%, p =
      0.022), as well as levels of C-reactive protein (139.60 vs. 107.61 mg/dL, p =
      0.022) were higher in the nafcillin group. All-cause 28-day mortality was
      significantly high in the glycopeptide group (7.7 vs. 20.6%, p = 0.013).
      CONCLUSION: In patients with MSSA bacteremia, all-cause 28-day mortality rate was
      higher in a group treated with glycopeptides than in a group treated with
      nafcillin. Therefore, the use of nafcillin should be considered as a definitive
      therapy for MSSA bacteremia.

PMID- 29378566
TI  - Bridging gaps in everyday life - a free-listing approach to explore the variety
      of activities performed by physiotherapists in specialized palliative care.
AB  - BACKGROUND: A growing body of studies indicate benefits of physiotherapy for
      patients in palliative care, for symptom relief and wellbeing. Though
      physiotherapists are increasingly acknowledged as important members of palliative
      care teams, they are still an underutilized source and not fully recognized. The
      aim of this study was to explore the variety of activities described by
      physiotherapists in addressing the needs and problems of patients and their
      families in specialized palliative care settings. METHODS: Using a free-listing
      approach, ten physiotherapists working in eight specialized palliative care
      settings in Sweden described as precisely and in as much detail as possible
      different activities in which patients and their families were included (directly
      or indirectly) during 10 days. The statements were entered into NVivo and
      analysed using qualitative content analysis. Statements containing more than one
      activity were categorized per activity. RESULTS: In total, 264 statements,
      containing 504 varied activities, were coded into seven categories: Counteracting
      a declining physical function; Informing, guiding and educating; Observing,
      assessing and evaluating; Attending to signs and symptoms; Listening, talking
      with and understanding; Caring for basic needs; and Organizing, planning and
      coordinating. In practice, however, the activities were intrinsically interwoven.
      The activities showed how physiotherapists aimed, through care for the body, to
      address patients' physical, psychological, social and existential needs,
      counteracting the decline in a patient's physical function and wellbeing. The
      activities also revealed a great variation, in relation not only to what they
      did, but also to their holistic and inseparable nature with regard to why, how,
      when, where, with whom and for whom the activities were carried out, which points
      towards a well-adopted person-centred palliative care approach. CONCLUSIONS: The
      study provides hands-on descriptions of how person-centred palliative care is
      integrated in physiotherapists' everyday activities. Physiotherapists in
      specialized palliative care help patients and families to bridge the gap between
      their real and ideal everyday life with the aim to maximize security, autonomy
      and wellbeing. The concrete examples included can be used in understanding the
      contribution of physiotherapists to the palliative care team and inform future
      research interventions and outcomes.

PMID- 29378567
TI  - Does a provider payment method affect membership retention in a health insurance
      scheme? a mixed method study of Ghana's capitation payment for primary care.
AB  - BACKGROUND: Ghana introduced a National Health Insurance Scheme (NHIS) in 2003
      applying fee-for-service method for paying NHIS-credentialed health care
      providers. The National Health Insurance Authority (NHIA) later introduced
      diagnosis-related-grouping (DRG) payment to contain cost without much success.
      The NHIA then introduced capitation payment, a decision that attracted complaints
      of falling enrolment and renewal rates from stakeholders. This study was done to
      provide evidence on this trend to guide policy debate on the issue. METHODS: We
      applied mixed method design to the study. We did a trend analysis of NHIS
      membership data in Ashanti, Volta and Central regions to assess growth rate;
      performed independent-sample t-test to compare sample means of the three regions
      and analysed data from individual in-depth interviews to determine any
      relationship between capitation payment and subscribers' renewal decision.
      RESULTS: Results of new enrolment data analysis showed differences in mean growth
      rates between Ashanti (M = 30.15, SE 3.03) and Volta (M = 40.72, SE 3.10), p =
      0.041; r = 0. 15; and between Ashanti and Central (M = 47.38, SE6.49) p = 0.043;
      r = 0. 42. Analysis of membership renewal data, however, showed no significant
      differences in mean growth rates between Ashanti (M = 65.47, SE 6.67) and Volta
      (M = 69.29, SE 5.04), p = 0.660; r = 0.03; and between Ashanti and Central (M =
      50.51, SE 9.49), p = 0.233. Analysis of both new enrolment and renewal data also
      showed no significant differences in mean growth rates between Ashanti (M = -
      13.76, SE 17.68) and Volta (M = 5.48, SE 5.50), p = 0.329; and between Ashanti
      and Central (M = - 6.47, SE 12.68), p = 0.746. However, capitation payment had
      some effect in Ashanti compared with Volta (r = 0. 12) and Central (r = 0. 14);
      but could not be sustained beyond 2012. Responses from the in-depth interviews
      did not also show that capitation payment is a key factor in subscribers' renewal
      decision. CONCLUSION: Capitation payment had a small but unsustainable effect on
      membership growth rate in the Ashanti region. Factors other than capitation
      payment may have played a more significant role in subscribers' enrolment and
      renewal decisions in the Ashanti region of Ghana.

PMID- 29378568
TI  - The five-year costs and benefits of extended psychological and psychiatric
      assessment versus standard intake interview for women with comorbid substance use
      disorders treated in compulsory care in Sweden.
AB  - BACKGROUND: Women with comorbid substance use disorders are an extremely
      vulnerable group having an increased relative risk of negative outcomes such as
      incarceration, morbidity and mortality. In Sweden, women with comorbid substance
      use disorders may be placed in compulsory care for substance abuse treatment.
      Clinical intake assessment procedures are a distinct aspect of clinical practice
      and are a foundation upon which client motivation and continued treatment occurs.
      METHOD: The current study is a naturalistic quasi-experiment and aims to assess
      the five-year costs and benefits of a standard intake interview versus an
      extended psychological and psychiatric assessment for a group of chronic
      substance abusing women placed in compulsory care in Sweden between 1997 and
      2000. Official register data on criminal activity, healthcare use, compulsory
      care stays and other services was retrieved and all resources used by study
      participants from date of index care episode was valued. In addition, the cost of
      providing the intake assessment was estimated. RESULTS: Results show that the
      extended assessment resulted in higher net costs over five years of between
      256,000 and 557,000 SEK per person for women placed in care via the Law on
      Compulsory Care for Substance Abusers (LVM). Higher assessment costs made up a
      portion of this cost. The majority of this cost (47-57%) falls on the local
      municipality (social welfare) and 11.6-13.7% falls on the individual patient.
      CONCLUSIONS: Solid evidence supporting the clinical utility or incremental
      validity of assessment for improving treatment outcomes in this setting was not
      confirmed.

PMID- 29378569
TI  - Synthesis of 4-(dimethylamino)pyridine propylthioacetate coated gold
      nanoparticles and their antibacterial and photophysical activity.
AB  - BACKGROUND: Gold nanoparticles are useful candidate for drug delivery
      applications and are associated with enhancement in the bioavailability of coated
      drugs and/or therapeutic agent. Since, heterocyclic compounds are known to
      exhibit antimicrobial potential against variety of pathogens, we designed this
      study to evaluate the antibacterial effects of gold nanoparticles conjugation
      with new synthesized cationic ligand; 4-Dimethyl aminopyridinium
      propylthioacetate (DMAP-PTA) in comparison with pure compound and antibiotic drug
      Pefloxacin. Antibacterial activity of DMAP-PTA coated gold nanoparticles was
      investigated against a fecal strain of E. coli (ATCC 8739). RESULTS: A new
      dimethyl aminopyridine based stabilizing agent named as DMAP-PTA was synthesized
      and used for stabilization of gold nanoparticles. Gold nanoparticles coated with
      DMAP-PTA abbreviated as DMAP-PTA-AuNPs were thoroughly characterized by UV
      visible, FT-IR spectroscopic methods and transmission electron microscope before
      biological assay. DMAP-PTA, DMAP-PTA-AuNPs and Pefloxacin were examined for their
      antibacterial potential against E. coli, and the minimum inhibitory concentration
      (MIC) was determined to be 300, 200 and 50 ug/mL respectively. Gold nanoparticles
      conjugation was found to significantly enhance the antibacterial activity of DMAP
      PTA as compared to pure compound. Moreover, effects of DMAP-PTA-AuNPs on the
      antibacterial potential of Pefloxacin was also evaluated by combination therapy
      of 1:1 mixture of DMAP-PTA-AuNPs and Pefloxacin against E. coli in a wide range
      of concentrations from 5 to 300 ug/mL. The MIC of Pefloxacin + DMAP-PTA-AuNPs
      mixture was found to be 25 ug/mL as compared to Pefloxacin alone (50 ug/mL),
      which clearly indicates that DMAP-PTA-AuNPs increased the potency of Pefloxacin.
      AFM analysis was also carried out to show morphological changes occur in bacteria
      before and after treatment of test samples. Furthermore, DMAP-PTA-AuNPs showed
      high selectivity towards Pefloxacin in spectrophotometric drug recognition
      studies which offers tremendous potential for analytical applications.
      CONCLUSIONS: Gold nanoparticles conjugation was shown to enhance the
      antibacterial efficacy of DMAP-PTA ligand, while DMAP-PTA-AuNPs also induced
      synergistic effects on the potency of Pefloxacin against E. coli. DMAP-PTA-AuNPs
      were also developed as Pefloxacin probes in recognizing the drug in blood and
      water samples in the presence of other drugs.

PMID- 29378571
TI  - High incidence and early onset of nivolumab-induced pneumonitis: four case
      reports and literature review.
AB  - BACKGROUND: Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody
      used as an immune checkpoint inhibitor, is commonly employed for its anti-tumor
      effects against various types of malignant tumors. However, its administration is
      complicated by immune-related adverse events (irAEs), including pneumonitis. CASE
      PRESENTATION: We present a case series of four patients with malignant melanoma,
      non-small cell lung cancer, and hypopharyngeal carcinoma who demonstrated
      pneumonitis induced by nivolumab, and further review clinicopathological
      characteristics of these patients in comparison with those of previously reported
      patients with nivolumab-induced pneumonitis. In our series, 20% of patients who
      were treated with nivolumab developed pneumonitis, all of which occurred
      approximately 2 weeks after the initiation of nivolumab treatment. Prompt
      recognition of the nivolumab-induced pneumonitis allowed for successful
      resolution. Computed tomography scan images of the patients demonstrated
      predominantly cryptogenic organizing pneumonia patterns. All patients were males,
      who had been heavily treated with antitumor drugs prior to nivolumab.
      CONCLUSIONS: Our case series showed that nivolumab had a high incidence of drug
      induced pneumonitis with early onset, supporting the need for renewed attention
      to nivolumab-induced pneumonitis, particularly in patients with a history of
      heavy antitumor treatments.

PMID- 29378570
TI  - Improving early audiological intervention via newborn hearing screening in
      Belgium.
AB  - BACKGROUND: Newborn hearing screening programs aim to lower the ages at
      audiological intervention among hearing-impaired children. In Wallonia and
      Brussels (Belgium), audiological intervention data are not collected in the
      screening program, and the ages at initiating audiological care have never been
      assessed. This study aimed to assess the evolution in the ages at initiating
      audiological intervention in the context of a newborn hearing screening program
      implementation. METHODS: This population-based descriptive study used data from
      the Belgian healthcare billing database. The main outcomes were the children's
      ages at the initial audiological assessment, hearing-aid fitting, and cochlear
      implantation. Results were compared to the same outcomes from another Belgian
      regional program (Flanders) that was implemented one decade earlier. Annual birth
      cohorts from 2006 to 2011 were included in the study. RESULTS: In Wallonia
      Brussels, the median ages for all outcomes tended to decrease over time but
      remained higher than in Flanders for each birth cohort. For all outcomes except
      the hearing-aid fitting, differences in median ages between the two regions
      became less pronounced during the study period. In 2006, < 23% of the children
      from Wallonia-Brussels received any audiological care before the age of 12 months
      and these proportions were approximately 2-fold greater in the subsequent birth
      cohorts. For all outcomes, early care (< 12 months) was typically delivered less
      frequently in Wallonia-Brussels, compared to the delivery in Flanders. These
      region-specific differences exhibited a decreasing trend over time, and
      statistically significant differences were less common in the later birth
      cohorts. CONCLUSIONS: We conclude that the hearing screening program in Wallonia
      and Brussels promoted earlier audiological intervention among hearing-impaired
      children. However, milestones recommended by experts for an early intervention
      were not totally encountered. We also recommend collecting audiological
      intervention data as part of this program, which can facilitate more accurate and
      regular program evaluation.

PMID- 29378572
TI  - CRISPR/dCas9-mediated transcriptional improvement of the biosynthetic gene
      cluster for the epothilone production in Myxococcus xanthus.
AB  - BACKGROUND: The CRISPR/dCas9 system is a powerful tool to activate the
      transcription of target genes in eukaryotic or prokaryotic cells, but lacks
      assays in complex conditions, such as the biosynthesis of secondary metabolites.
      RESULTS: In this study, to improve the transcription of the heterologously
      expressed biosynthetic genes for the production of epothilones, we established
      the CRISPR/dCas9-mediated activation technique in Myxococcus xanthus and analyzed
      some key factors involving in the CRISPR/dCas9 activation. We firstly optimized
      the cas9 codon to fit the M. xanthus cells, mutated the gene to inactivate the
      nuclease activity, and constructed the dCas9-activator system in an epothilone
      producer. We compared the improvement efficiency of different sgRNAs on the
      production of epothilones and the expression of the biosynthetic genes. We also
      compared the improvement effects of different activator proteins, the omega and
      alpha subunits of RNA polymerase, and the sigma factors sigma54 and CarQ. By
      using a copper-inducible promoter, we determined that higher expressions of dCas9
      activator improved the activation effects. CONCLUSIONS: Our results showed that
      the CRISPR/dCas-mediated transcription activation is a simple and broadly
      applicable technique to improve the transcriptional efficiency for the production
      of secondary metabolites in microorganisms. This is the first time to construct
      the CRISPR/dCas9 activation system in myxobacteria and the first time to assay
      the CRISPR/dCas9 activations for the biosynthesis of microbial secondary
      metabolites.

PMID- 29378573
TI  - Cortisol modulates inflammatory responses in LPS-stimulated RAW264.7 cells via
      the NF-kappaB and MAPK pathways.
AB  - BACKGROUND: The uteruses of most dairy cattle are easily infected by bacteria,
      especially gram-negative bacteria, following parturition. Macrophages are
      important cells of the immune system and play a critical role in the inflammatory
      response. In addition, cortisol levels become significantly increased due to the
      stress of parturition in dairy cattle, and cortisol is among the most widely used
      and effective therapies for many inflammatory diseases. In this study, we
      assessed the anti-inflammatory effects and potential molecular mechanisms of
      cortisol using a Lipopolysaccharide (LPS)-induced RAW264.7 macrophage cell line.
      RESULTS: Cortisol significantly suppressed the production of prostaglandin E2
      (PGE2) and decreased the gene and protein expression of inducible NO synthase
      (iNOS) and cyclooxygenase-2 (COX-2) in a dose-dependent manner. Moreover,
      cortisol inhibited the mRNA expression of pro-inflammatory cytokines including
      tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and
      interleukin-6 (IL-6) and decreased IL-1beta secretion in an LPS-treated RAW264.7
      macrophage cell line. Moreover, we found that cortisol suppressed nuclear factor
      kappa B (NF-kappaB) signaling in RAW264.7 macrophages stimulated with LPS. This
      suppression was mediated by the inhibition of IkappaBalpha degradation and NF
      kappaB p65 phosphorylation. In addition, cortisol also suppressed the
      phosphorylation of mitogen-activated protein kinases (MAPK) such as extracellular
      signal-regulated kinase (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase/stress
      activated protein kinase (JNK). CONCLUSIONS: These results suggest that high
      cortisol levels can attenuate LPS-induced inflammatory responses in the RAW264.7
      macrophage cell line by regulating the NF-kappaB and MAPK signaling pathways.

PMID- 29378574
TI  - Anticipating the potential for positive uptake and adaptation in the
      implementation of a publicly funded online STBBI testing service: a qualitative
      analysis.
AB  - BACKGROUND: Online health services are a rapidly growing aspect of public health
      provision, including testing for sexually transmitted and other blood-borne
      infections (STBBI). Generally, healthcare providers, policymakers, and clients
      imbue online approaches with great positive potential (e.g., encouraging clients'
      agency; providing cost-effective services to more clients). However, the promise
      of online health services may vary across contexts and be perceived in negative
      or ambiguous ways (e.g., risks to 'gold standard' care provision; loss of
      provider control over an intervention; uncertainty related to budget
      implications). This study examines attitudes and perceptions regarding the
      development of a novel online STBBI testing service in Vancouver, Canada. We
      examine the perceptions about the intervention's potential by interviewing
      practitioners and planners who were engaged in the development and initial
      implementation of this testing service. METHODS: We conducted in-depth interviews
      with 37 healthcare providers, administrators, policymakers, and community-based
      service providers engaged in the design and launch of the new online STBBI
      testing service. We also conducted observations during planning and
      implementation meetings for the new service. Thematic analysis techniques were
      employed to identify codes and broader discursive themes across the interview
      transcripts and observation notes. RESULTS: Some study participants expressed
      concern that the potential popularity of the new testing service might increase
      demand on existing sexual health services or become fiscally unsustainable.
      However, most participants regarded the new service as having the potential to
      improve STBBI testing in several ways, including reducing waiting times,
      enhancing privacy and confidentiality, appealing to more tech-savvy sub
      populations, optimizing the redistribution of demands on face-to-face service
      provision, and providing patient-centred technology to empower clients to seek
      testing. CONCLUSIONS: Participants perceived this online STBBI testing service to
      have the potential to improve sexual health care provision. But, they also
      anticipated actions-and-reactions, revealing a need to monitor ongoing
      implementation dynamics. They also identified the larger, potentially system
      transforming dimension of the new technology, which enables new system drivers
      (consumers) and reduces the amount of control health care providers have over
      online STBBI testing compared to conventional in-person testing.

PMID- 29378575
TI  - Effects of Omegaven(r), EPA, DHA and oxaliplatin on oesophageal adenocarcinoma
      cell lines growth, cytokine and cell signal biomarkers expression.
AB  - BACKGROUND: There is limited evidence assessing the effects of omega-3
      polyunsaturated fatty acids (PUFAs) on oesophageal adenocarcinoma, both in vitro
      and in vivo. We evaluated the effects of the omega-3 PUFA and oxaliplatin on OE33
      and OE19 cells. METHOD: The two oesophageal cells were treated with Omegaven(r)
      (fish oil emulsion), EPA, DHA and oxaliplatin and incubated for up to 144 h.
      RESULTS: The following inhibitory effects were observed on OE33 cells: EPA
      reduced cell growth by 39% (p = 0.001), DHA by 59% (p < 0.000) and Oxaliplatin by
      77% (p < 0.000). For OE19 cells, the EPA reduced growth by 1% (p = 0.992), DHA by
      26% (p = 0.019) and oxaliplatin by 76% (p < 0.000). For both cells, Omegaven(r)
      resulted in reduced cell growth at intermediate concentrations (20-40 MUM) and
      increased cell growth at low (10 MUM) and high (50 MUM) concentrations. DHA,
      Omegaven(r) and oxaliplatin were associated with significant downregulation of
      VEGF and p53 protein, and upregulation of p21 protein. DHA, Omegaven(r) and
      Oxaliplatin also led to significant downregulation of the total ERK1/2 and Akt
      proteins. CONCLUSION: DHA, Omegaven(r) and oxaliplatin were associated with
      downregulation of p53 and VEGF in both cells. Of the PUFAs studied, DHA alone or
      in combination (Omegaven(r)) had greater in vitro anti-cancer effects than EPA
      alone.

PMID- 29378576
TI  - Economic evaluation of type 2 diabetes prevention programmes: Markov model of low
      and high-intensity lifestyle programmes and metformin in participants with
      different categories of intermediate hyperglycaemia.
AB  - BACKGROUND: National guidance on preventing type 2 diabetes mellitus (T2DM) in
      the UK recommends low-intensity lifestyle interventions for individuals with
      intermediate categories of hyperglycaemia defined in terms of impaired fasting
      glucose (IFG) or 'at-risk' levels of HbA1c. In a recent systematic review of
      economic evaluations of such interventions, most studies had evaluated intensive
      trial-based lifestyle programmes in participants with impaired glucose tolerance
      (IGT). This study examines the costs and effects of different intensity lifestyle
      programmes and metformin in participants with different categories of
      intermediate hyperglycaemia. METHODS: We developed a decision tree and Markov
      model (50-year horizon) to compare four approaches, namely (1) a low-intensity
      lifestyle programme based on current NICE guidance, (2) a high-intensity
      lifestyle programme based on the US Diabetes Prevention Program, (3) metformin,
      and (4) no intervention, modelled for three different types of intermediate
      hyperglycaemia (IFG, IGT and HbA1c). A health system perspective was adopted and
      incremental analysis undertaken at an individual and population-wide level,
      taking England as a case study. RESULTS: Low-intensity lifestyle programmes were
      the most cost-effective (L44/QALY, L195/QALY and L186/QALY compared to no
      intervention in IGT, IFG and HbA1c, respectively). Intensive lifestyle
      interventions were also cost-effective compared to no intervention (L2775/QALY,
      L6820/QALY and L7376/QALY, respectively, in IGT, IFG and HbA1c). Metformin was
      cost-effective relative to no intervention (L5224/QALY, L6842/QALY and L372/QALY
      in IGT, IFG and HbA1c, respectively), but was only cost-effective relative to
      other treatments in participants identified with HbA1c. At a willingness-to-pay
      threshold of L20,000/QALY, low- and high-intensity lifestyle programmes were cost
      effective 98%, 99% and 98% and 81%, 81% and 71% of the time in IGT, IFG and
      HbA1c, respectively. An England-wide programme for 50-59 year olds could reduce
      T2DM incidence by < 3.5% over 50 years and would cost 0.2-5.2% of the current
      diabetes budget for 2-9 years. DISCUSSION: This analysis suggests that current
      English national policy of low-intensity lifestyle programmes in participants
      with IFG or HbA1c will be cost-effective and have the most favourable budget
      impact, but will prevent only a fraction of cases of T2DM. Additional approaches
      to prevention need to be investigated urgently.

PMID- 29378577
TI  - Risks predicting prolonged hospital discharge boarding in a regional acute care
      hospital.
AB  - BACKGROUND: Prolonged hospital discharge boarding can impact patient flow
      resulting in upstream Emergency Department crowding. We aim to determine the
      risks predicting prolonged hospital discharge boarding and their direct and
      indirect effects on patient flow. METHODS: Retrospective review of a single
      hospital discharge database was conducted. Variables including type of
      disposition, disposition boarding time, case management consultation, discharge
      medications prescriptions, severity of illness, and patient homeless status were
      analyzed in a multivariate logistic regression model. Hospital charges, potential
      savings of hospital bed hours, and whether detailed discharge instructions
      provided adequate explanations to patients were also analyzed. RESULTS: A total
      of 11,527 admissions was entered into final analysis. The median discharge
      boarding time was approximately 2 h. Adjusted Odds Ratio (AOR) of patients
      transferring to other hospitals was 7.45 (95% CI 5.35-10.37), to court or law
      enforcement custody was 2.51 (95% CI 1.84-3.42), and to a skilled nursing
      facility was 2.48 (95% CI 2.10-2.93). AOR was 0.57 (95% CI 0.47-0.71) if the
      disposition order was placed during normal office hours (0800-1700). AOR of early
      case management consultation was 1.52 (95% CI 1.37-1.68) versus 1.73 (95% CI 1.03
      2.89) for late consultation. Eighty-eight percent of patients experiencing
      discharge boarding times within 2 h of disposition expressed positive responses
      when questioned about the quality of explanations of discharge instructions and
      follow-up plans based on satisfaction surveys. Similar results (86% positive
      response) were noted among patients whose discharge boarding times were prolonged
      (> 2 h, p = 0.44). An average charge of $6/bed/h was noted in all hospital
      discharges. Maximizing early discharge boarding (<= 2 h) would have resulted in
      16,376 hospital bed hours saved thereby averting $98,256.00 in unnecessary dwell
      time charges in this study population alone. CONCLUSION: Type of disposition,
      case management timely consultation, and disposition to discharge dwell time
      affect boarding and patient flow in a tertiary acute care hospital. Efficiency of
      the discharge process did not affect patient satisfaction relative to the
      perceived quality of discharge instruction and follow-up plan explanations.
      Prolonged disposition to discharge intervals result in unnecessary hospital bed
      occupancy thereby negatively impacting hospital finances while delivering no
      direct benefit to patients.

PMID- 29378578
TI  - Artificial intelligence on the identification of risk groups for osteoporosis, a
      general review.
AB  - INTRODUCTION: The goal of this paper is to present a critical review on the main
      systems that use artificial intelligence to identify groups at risk for
      osteoporosis or fractures. The systems considered for this study were those that
      fulfilled the following requirements: range of coverage in diagnosis, low cost
      and capability to identify more significant somatic factors. METHODS: A
      bibliographic research was done in the databases, PubMed, IEEExplorer Latin
      American and Caribbean Center on Health Sciences Information (LILACS), Medical
      Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, and
      Science Direct searching the terms "Neural Network", "Osteoporosis Machine
      Learning" and "Osteoporosis Neural Network". Studies with titles not directly
      related to the research topic and older data that reported repeated strategies
      were excluded. The search was carried out with the descriptors in German,
      Spanish, French, Italian, Mandarin, Portuguese and English; but only studies
      written in English were found to meet the established criteria. Articles covering
      the period 2000-2017 were selected; however, articles prior to this period with
      great relevance were included in this study. DISCUSSION: Based on the collected
      research, it was identified that there are several methods in the use of
      artificial intelligence to help the screening of risk groups of osteoporosis or
      fractures. However, such systems were limited to a specific ethnic group, gender
      or age. For future research, new challenges are presented. CONCLUSIONS: It is
      necessary to develop research with the unification of different databases and
      grouping of the various attributes and clinical factors, in order to reach a
      greater comprehensiveness in the identification of risk groups of osteoporosis.
      For this purpose, the use of any predictive tool should be performed in different
      populations with greater participation of male patients and inclusion of a larger
      age range for the ones involved. The biggest challenge is to deal with all the
      data complexity generated by this unification, developing evidence-based
      standards for the evaluation of the most significant risk factors.

PMID- 29378579
TI  - Provider views on childhood obesity management in primary care settings: a mixed
      methods analysis.
AB  - BACKGROUND: Pediatric providers are key players in the treatment of childhood
      obesity, yet rates of obesity management in the primary care setting are low. The
      goal of this study was to examine the views of pediatric providers on conducting
      obesity management in the primary care setting, and identify potential resources
      and care models that could facilitate delivery of this care. METHODS: A mixed
      methods approach was utilized. Four focus groups were conducted with providers
      from a large pediatric network in San Diego County. Based on a priori and
      emerging themes, a questionnaire was developed and administered to the larger
      group of providers in this network. RESULTS: Barriers to conducting obesity
      management fell into four categories: provider-level/individual (e.g., lack of
      knowledge and confidence), practice-based/systems-level (e.g., lack of time and
      resources), parent-level (e.g., poor motivation and follow-up), and environmental
      (e.g., lack of access to resources). Solutions centered around implementing a
      team approach to care (with case managers and health coaches) and electronic
      medical record changes to include best practice guidelines, increased ease of
      documentation, and delivery of standardized handouts/resources. Survey results
      revealed only 23.8% of providers wanted to conduct behavioral management of
      obesity. The most requested support was the introduction of a health educator in
      the office to deliver a brief behavioral intervention. CONCLUSION: While
      providers recognize the importance of addressing weight during a well-child
      visit, they do not want to conduct obesity management on their own. Future
      efforts to improve health outcomes for pediatric obesity should consider
      implementing a collaborative care approach.

PMID- 29378580
TI  - Automatic QRS complex detection using two-level convolutional neural network.
AB  - BACKGROUND: The QRS complex is the most noticeable feature in the
      electrocardiogram (ECG) signal, therefore, its detection is critical for ECG
      signal analysis. The existing detection methods largely depend on hand-crafted
      manual features and parameters, which may introduce significant computational
      complexity, especially in the transform domains. In addition, fixed features and
      parameters are not suitable for detecting various kinds of QRS complexes under
      different circumstances. METHODS: In this study, based on 1-D convolutional
      neural network (CNN), an accurate method for QRS complex detection is proposed.
      The CNN consists of object-level and part-level CNNs for extracting different
      grained ECG morphological features automatically. All the extracted morphological
      features are used by multi-layer perceptron (MLP) for QRS complex detection.
      Additionally, a simple ECG signal preprocessing technique which only contains
      difference operation in temporal domain is adopted. RESULTS: Based on the MIT-BIH
      arrhythmia (MIT-BIH-AR) database, the proposed detection method achieves overall
      sensitivity Sen = 99.77%, positive predictivity rate PPR = 99.91%, and detection
      error rate DER = 0.32%. In addition, the performance variation is performed
      according to different signal-to-noise ratio (SNR) values. CONCLUSIONS: An
      automatic QRS detection method using two-level 1-D CNN and simple signal
      preprocessing technique is proposed for QRS complex detection. Compared with the
      state-of-the-art QRS complex detection approaches, experimental results show that
      the proposed method acquires comparable accuracy.

PMID- 29378581
TI  - Patient and provider perspectives inform an intervention to improve linkage to
      care for HIV patients in Ukraine.
AB  - BACKGROUND: Engagement with HIV medical care is critical to successful HIV
      treatment and prevention efforts. However, in Ukraine, delays in the timely
      initiation of HIV treatment hamper viral suppression. By January 01, 2016, only
      126,604 (57.5%) of the estimated 220,000 people living with HIV (PLWH) had
      registered for HIV care, and most (55.1%) of those who registered for HIV care in
      2015 did that at a late stage of infection. In the US, Anti-Retroviral Treatment
      and Access to Services (ARTAS) intervention successfully linked newly diagnosed
      PLWH to HIV services using strengths-based case management with a linkage
      coordinator. To tailor the ARTAS intervention for Ukraine, we conducted a
      qualitative study with patients and providers to understand barriers and
      facilitators that influence linkage to HIV care. METHODS: During September
      October 2014, we conducted 20 in-depth interviews with HIV-positive patients and
      two focus groups with physicians in infectious disease, sexually transmitted
      infection (STI), and addiction clinics in Dnipropetrovsk Region of Ukraine.
      Interviews and focus groups were audio-recorded and transcribed verbatim. We
      translated illustrative quotes into English. We used thematic analysis for the
      data analysis. RESULTS: Participants (20 patients and 14 physicians) identified
      multiple, mostly individual-level factors influencing HIV care initiation. Key
      barriers included lack of HIV knowledge, non-acceptance of HIV diagnosis, fear of
      HIV disclosure, lack of psychological support from health providers, and HIV
      stigma in community. Responsibility for one's health, health deterioration, and
      supportive provider communication were reported as facilitators to linkage to
      care. Expected benefits from the case management intervention included
      psychological support, HIV education, and help with navigating the segmented
      health system. CONCLUSIONS: The findings from the study will be used to optimize
      the ARTAS for the Ukrainian context. Our findings can also support future linkage
      to-care strategies in other countries of Eastern Europe and Central Asia.

PMID- 29378582
TI  - A novel one arm motorized walker for hemiplegic stroke survivors: a feasibility
      study.
AB  - BACKGROUND: A hemiplegic stroke survivor with a moderate to severe gait
      disturbance may have difficulty walking using a one-arm walker. This study aimed
      to test the safety and feasibility of a prototype one-arm motorized walker that
      uses a power-driven device to provide gait assistance to hemiplegic stroke
      survivors with moderate to severe gait disturbances. METHODS: A one-arm motorized
      walker with a power-driven device was developed and tested with respect to 10
      distinct variables, including weight, degrees of freedom, handle, handle
      substitution function, two-sided use function, variable handle height,
      redirecting function, electric moving parts through the handle control, brake
      function using the handle control, folding chairs, and design stability. Its
      safety and feasibility were tested in 19 hemiplegic stroke individuals using the
      Likert scale and a simple interview. RESULTS: The walker consists of a frame
      platform including a handle, electric motor for driving, one wheel for driving,
      two wheels for turning, unlocking sensor, driving button, and turning buttons.
      The walker is programmed so that a touch sensor in the handle can unlock the
      locking system. Furthermore, it is programmed so that a user can propel it by
      pushing the handle downward or pressing a button and can control directions for
      turning right or left by pressing buttons. Safety and performance testing was
      achieved for 10 separate variables, and a Likert scale score of 3.5 of 5 was
      recorded. CONCLUSION: This walker's novel design was developed for hemiplegic
      stroke survivors with moderate to severe gait disturbances. Our findings indicate
      that the walker is both safe and feasible for providing walking assistance to
      hemiplegic stroke survivors and establish the potential advantages of the one-arm
      motorized walker.

PMID- 29378583
TI  - Associations of childhood, maternal and household dietary patterns with childhood
      stunting in Ethiopia: proposing an alternative and plausible dietary analysis
      method to dietary diversity scores.
AB  - BACKGROUND: Identifying dietary patterns that consider the overall eating habits,
      rather than focusing on individual foods or simple counts of consumed foods,
      better helps to understand the combined effects of dietary components. Therefore,
      this study aimed to use dietary patterns, as an alternative method to dietary
      diversity scores (DDSs), and investigate their associations with childhood
      stunting in Ethiopia. METHODS: Mothers and their children aged under 5 years (n =
      3788) were recruited using a two-stage random cluster sampling technique in two
      regions of Ethiopia. Socio-demographic, dietary and anthropometric data were
      collected. Dietary intake was assessed using standardized dietary diversity
      tools. Household, maternal and child DDSs were calculated and dietary patterns
      were identified by tetrachoric (factor) analysis. Multilevel linear and Poisson
      regression analyses were applied to assess the association of DDSs and dietary
      patterns with height-for-age z score (HAZ) and stunting, respectively. RESULTS:
      The overall prevalence of stunting among children under-five was 38.5% (n =
      1459). We identified three dietary patterns each, for households ("fish, meat and
      miscellaneous", "egg, meat, poultry and legume" and "dairy, vegetable and
      fruit"), mothers ("plant-based", "egg, meat, poultry and legume" and "dairy,
      vegetable and fruit" and children ("grain based", "egg, meat, poultry and legume"
      and "dairy, vegetable and fruit"). Children in the third tertile of the household
      "dairy, vegetable and fruit" pattern had a 0.16 (beta = 0.16; 95% CI: 0.02, 0.30)
      increase in HAZ compared to those in the first tertile. A 0.22 (beta = 0.22; 95%
      CI: 0.06, 0.39) and 0.19 (beta = 0.19; 0.04, 0.33) increase in HAZ was found for
      those in the third tertiles of "dairy, vegetable and fruit" patterns of children
      24-59 months and 6-59 months, respectively. Those children in the second (beta = 
      0.17; 95% CI: -0.31, -0.04) and third (beta = -0.16; 95% CI: -0.30, -0.02)
      tertiles of maternal "egg, meat, poultry and legume" pattern had a significantly
      lower HAZ compared to those in the first tertile. No significant associations
      between the household and child "egg, meat, poultry and legume" dietary patterns
      with HAZ and stunting were found. Statistically non-significant associations were
      found between household, maternal and child DDSs, and HAZ and stunting.
      CONCLUSION: A higher adherence to a "dairy, vegetable and fruit" dietary pattern
      is associated with increased HAZ and reduced risk of stunting. Dietary pattern
      analysis methods, using routinely collected dietary data, can be an alternative
      approach to DDSs in low resource settings, to measure dietary quality and in
      determining associations of overall dietary intake with stunting.

PMID- 29378584
TI  - Development of a 5As-based technology-assisted weight management intervention for
      veterans in primary care.
AB  - BACKGROUND: Obesity is a worldwide epidemic, and its prevalence is higher among
      Veterans in the United States. Based on our prior research, primary care teams at
      a Veterans Affairs (VA) hospital do not feel well-equipped to deliver effective
      weight management counseling and often lack sufficient time. Further, effective
      and intensive lifestyle-based weight management programs (e.g. VA MOVE! program)
      are underutilized despite implementation of systematic screening and referral at
      all VA sites. The 5As behavior change model (Assess, Advise, Agree, Assist,
      Arrange) is endorsed by the United States Preventive Service Task Force for use
      in counseling patients about weight management in primary care and reimbursed by
      Medicare. In this paper, we describe the iterative development of a technology
      assisted intervention designed to provide primary care-based 5As counseling
      within Patient-Centered Medical Homes without overburdening providers/healthcare
      teams. METHODS: Thematic analyses of prior formative work (focus groups with
      patients [n = 54] and key informant interviews with staff [n = 25]) helped to
      create a technology-assisted, health coaching intervention called Goals for
      Eating and Moving (GEM). To further develop the intervention, we then conducted
      two rounds of testing with previous formative study participants (n = 5 for Round
      1, n = 5 for Round 2). Each session included usability testing of prototypes of
      the online GEM tool, pilot testing of 5As counseling by a Health Coach, and a
      post-session open-ended interview. RESULTS: Three main themes emerged from
      usability data analyses: participants' emotional responses, tool language, and
      health literacy. Findings from both rounds of usability testing, pilot testing,
      as well as the open-ended interview data, were used to finalize protocols for the
      full intervention in the clinic setting to be conducted with Version 3 of the GEM
      tool. CONCLUSIONS: The use of qualitative research methods and user-centered
      design approaches enabled timely detection of salient issues to make iterative
      improvements to the intervention. Future studies will determine whether this
      intervention can increase enrollment in intensive weight management programs and
      promote clinically meaningful weight loss in both Veterans and in other patient
      populations and health systems.

PMID- 29378586
TI  - South African primary health care allied health clinical practice guidelines: the
      big picture.
AB  - BACKGROUND: Good quality clinical practice guidelines (CPGs) are a vehicle to
      implementing evidence into allied health (AH) care. This paper reports on the
      current 'state of play' of CPGs in a lower-to-middle-income country (South
      Africa), where primary healthcare (PHC) AH activities face significant challenges
      in terms of ensuring quality service delivery in the face of huge PHC need.
      METHODS: A qualitative study was conducted, using semi-structured interviews with
      purposively-sampled individuals involved in AH PHC CPGs in South Africa. They
      included national and state government policy-makers, academics and educators,
      service managers, clinicians, representatives of professional associations,
      technical writers, and members of informal professional networks. The interview
      data was transcribed and de-identified, and analysed descriptively by hand
      coding. The COREQ statement guided study conduct and reporting. A framework to
      guide research in other countries into perspectives of AH PHC CPG activities was
      established. RESULTS: Of the 32 invited, 29 people participated: of these 25 were
      interviewed and four provided meeting notes. Most participants had multiple
      professional roles, being engaged concurrently in clinical practice, academia,
      professional associations and / or government. Key themes comprised Players (sub
      themes of sampling frame, participants, advice, role players and collaboration);
      Guidance (sub-themes of nomenclature, drivers, purpose, evidence sources) and
      Role of AH in PHC (sub-themes of discipline groupings, disability and
      rehabilitation, AH recognition). CONCLUSION: There was consistently-expressed
      desire for quality guidance to support better quality AH PHC activities around
      the country. However no international CPGs were used, and there were no South
      African CPGs specific to local PHC AH practice. The guidance gap was filled by
      non-evidence-based documents produced often without training, to deal with
      specific clinical situations. This led to frustration, duplication and
      fragmentation of effort, confusing nomenclature, and an urgent need for
      standardised and agreed guidance. We provided a standardised framework to capture
      perspectives on CPGs activities in other AH PHC settings.

PMID- 29378585
TI  - Barriers and facilitators to implementation, uptake and sustainability of
      community-based health insurance schemes in low- and middle-income countries: a
      systematic review.
AB  - BACKGROUND: Community-based health insurance (CBHI) has evolved as an alternative
      health financing mechanism to out of pocket payments in low- and middle-income
      countries (LMICs), particularly in areas where government or employer-based
      health insurance is minimal. This systematic review aimed to assess the barriers
      and facilitators to implementation, uptake and sustainability of CHBI schemes in
      LMICs. METHODS: We searched six electronic databases and grey literature. We
      included both quantitative and qualitative studies written in English language
      and published after year 1992. Two reviewers worked in duplicate and
      independently to complete study selection, data abstraction, and assessment of
      methodological features. We synthesized the findings based on thematic analysis
      and categorized according to the ecological model into individual, interpersonal,
      community and systems levels. RESULTS: Of 15,510 citations, 51 met the
      eligibility criteria. Individual factors included awareness and understanding of
      the concept of CBHI, trust in scheme and scheme managers, perceived service
      quality, and demographic characteristics, which influenced enrollment and
      sustainability. Interpersonal factors such as household dynamics, other family
      members enrolled in the scheme, and social solidarity influenced enrollment and
      renewal of membership. Community-level factors such as culture and community
      involvement in scheme development influenced enrollment and sustainability of
      scheme. Systems-level factors encompassed governance, financial and delivery
      arrangement. Government involvement, accountability of scheme management, and
      strong policymaker-implementer relation facilitated implementation and
      sustainability of scheme. Packages that covered outpatient and inpatient care and
      those tailored to community needs contributed to increased enrollment. Amount and
      timing of premium collection was reported to negatively influence enrollment
      while factors reported as threats to sustainability included facility bankruptcy,
      operating on small budgets, rising healthcare costs, small risk pool, irregular
      contributions, and overutilization of services. At the delivery level,
      accessibility of facilities, facility environment, and health personnel
      influenced enrollment, service utilization and dropout rates. CONCLUSION: There
      are a multitude of interrelated factors at the individual, interpersonal,
      community and systems levels that drive the implementation, uptake and
      sustainability of CBHI schemes. We discuss the implications of the findings at
      the policy and research level. TRIAL REGISTRATION: The review protocol is
      registered in PROSPERO International prospective register of systematic reviews
      (ID =  CRD42015019812 ).

PMID- 29378587
TI  - Prevalence and characteristics of COPD among pneumoconiosis patients at an
      occupational disease prevention institute: a cross-sectional study.
AB  - BACKGROUND: Pneumoconiosis may play an important role in the development of
      chronic obstructive pulmonary disease (COPD), and the complication of COPD may
      impose a heavy burden of illness. METHODS: The study was conducted in Hunan
      Province in China from December 1, 2015, to December 1, 2016. Consecutive
      underground male pneumoconiosis patients employed for at least 1 year were
      recruited from the Hunan Occupational Disease Prevention Institute. Patient
      information, respiratory symptoms and clinical data were collected using a
      structured questionnaire. The diagnosis of COPD were assessed using the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. Logistic
      regression analyses were conducted to examine the clinical and demographic risk
      factors of COPD among pneumoconiosis patients. RESULTS: The prevalence of COPD in
      our sample of pneumoconiosis patients was 18.65% (119/638). In pneumoconiosis
      patients with and without smoking history, the prevalence of COPD was 19.32 and
      16.77%. Compared with non-COPD patients, those with COPD are older in age, have
      longer exposure time, have lower body mass index (BMI), have a higher smoking
      index and have worse pulmonary function (all p < 0.05). For the five respiratory
      symptoms (cough, sputum, wheeze, dyspnea, and chest tightness), only the presence
      of wheeze and the severity scores for wheeze or dyspnea showed significant
      differences between the COPD and non-COPD groups (p < 0.01). Multivariate
      logistic regression analysis revealed that advanced pneumoconiosis category,
      older age and the presence of wheeze symptoms were significant risk factors for
      the development of COPD among pneumoconiosis patients. CONCLUSION: Pneumoconiosis
      patients are at a high risk of COPD, and pneumoconiosis patients with COPD may
      suffer more severe respiratory symptoms, such as wheeze and dyspnea, than
      patients without COPD. Advanced pneumoconiosis category, older age and the
      presence of wheeze symptoms are associated with an increased risk of COPD in
      pneumoconiosis. We proposed that a routine assessment of lung function is
      necessary for timely and adequate clinical management.

PMID- 29378588
TI  - Plasmodium species differentiation by non-expert on-line volunteers for remote
      malaria field diagnosis.
AB  - BACKGROUND: Routine field diagnosis of malaria is a considerable challenge in
      rural and low resources endemic areas mainly due to lack of personnel, training
      and sample processing capacity. In addition, differential diagnosis of Plasmodium
      species has a high level of misdiagnosis. Real time remote microscopical
      diagnosis through on-line crowdsourcing platforms could be converted into an
      agile network to support diagnosis-based treatment and malaria control in low
      resources areas. This study explores whether accurate Plasmodium species
      identification-a critical step during the diagnosis protocol in order to choose
      the appropriate medication-is possible through the information provided by non
      trained on-line volunteers. METHODS: 88 volunteers have performed a series of
      questionnaires over 110 images to differentiate species (Plasmodium falciparum,
      Plasmodium ovale, Plasmodium vivax, Plasmodium malariae, Plasmodium knowlesi) and
      parasite staging from thin blood smear images digitalized with a smartphone
      camera adapted to the ocular of a conventional light microscope. Visual cues
      evaluated in the surveys include texture and colour, parasite shape and red blood
      size. RESULTS: On-line volunteers are able to discriminate Plasmodium species (P.
      falciparum, P. malariae, P. vivax, P. ovale, P. knowlesi) and stages in thin
      blood smears according to visual cues observed on digitalized images of
      parasitized red blood cells. Friendly textual descriptions of the visual cues and
      specialized malaria terminology is key for volunteers learning and efficiency.
      CONCLUSIONS: On-line volunteers with short-training are able to differentiate
      malaria parasite species and parasite stages from digitalized thin smears based
      on simple visual cues (shape, size, texture and colour). While the accuracy of a
      single on-line expert is far from perfect, a single parasite classification
      obtained by combining the opinions of multiple on-line volunteers over the same
      smear, could improve accuracy and reliability of Plasmodium species
      identification in remote malaria diagnosis.

PMID- 29378589
TI  - Patients' perceptions of interactions with hospital staff are associated with
      hospital readmissions: a national survey of 4535 hospitals.
AB  - BACKGROUND: Reducing 30-day hospital readmissions has become a focus of the
      current national payment policies. Medicare requires that hospitals collect and
      report patients' experience with their care as a condition of payment. However,
      the extent to which patients' experience with hospital care is related to
      hospital readmission is unknown. METHODS: We established multivariate regression
      models in which 30-day risk-adjusted readmission rates were the dependent
      variables and patients' perceptions of the responsiveness of the hospital staff
      and communication (as measured by the Hospital Consumer Assessment of Healthcare
      Providers and Systems (HCAHPS) scores) were the independent variables of
      interest. We selected six different clinical conditions for analyses, including
      acute myocardial infarction (AMI), chronic obstructive pulmonary disease (COPD),
      heart failure, hip/knee surgery, pneumonia, and stroke. Data included all acute
      care hospitals reporting in Hospital Compare in 2014. RESULTS: The number of
      hospitals with reported readmissions ranged from 2234 hospitals for AMI to 3758
      hospitals for pneumonia. The average 30-day readmission rates ranged from 5.19%
      for knee/hip surgery to 22.7% for COPD. Patient experience of hospital-staff
      responsiveness as "top-box" ranged from 64% to 67% across the six clinical
      conditions, communication with nurses ranged from 77% to 79% and communication
      with doctors ranged from 80% to 81% (higher numbers are better). Our finding
      suggests that hospitals with better staff responsiveness were significantly more
      likely to have lower 30-day readmissions for all conditions. The effect size
      depended on the baseline readmission rates, with the largest effect on hospitals
      in the upper 75th quartile. A ten-percentage-point increase in staff
      responsiveness led to a 0.03-0.18 percentage point decrease in readmission rates.
      We found that neither communication with physicians nor communication with nurses
      was significantly associated with hospital readmissions. CONCLUSIONS: Our
      findings suggest that elements of care related to staff responsiveness during
      patients' stay may influence rehospitalization rates. Changes in staff
      responsiveness may offer an additional tool for hospitals to employ ongoing
      efforts to achieve reductions in readmissions, an important objective both
      financially and for patient health outcomes.

PMID- 29378590
TI  - Patient satisfaction, patients leaving hospital against medical advice and
      mortality in Italian university hospitals: a cross-sectional analysis.
AB  - BACKGROUND: Healthcare systems are increasingly focusing on outcomes that are the
      endpoints of care: patient health status and patient satisfaction. The
      availability of patient satisfaction (PS) data has encouraged research on its
      relationship with other outcomes, such as mortality. In Italy, an inter-regional
      performance evaluation system (IRPES) provides 13 regional healthcare systems
      with a multidimensional assessment of appropriateness, efficiency, financial
      sustainability, effectiveness, and equity. For university hospitals, IRPES
      includes the percentage of patients leaving hospital against medical advice
      (PLHAMA) and mortality rates at the ward level. This paper investigates the
      relationship between PS and PLHAMA across and within regional healthcare systems
      in Italy. Secondly, PLHAMA is used as a PS proxy to investigate its relationship
      with mortality at the ward level in the IRPES university hospitals. METHODS:
      PLHAMA and mortality rates were gathered from administrative data, and PS scores
      from patient surveys. We explored the association between PS and PLHAMA through a
      correlation analysis, using data for the 13 IRPES regions. We tested this
      relationship also at the clinical directorate level in 28 hospitals in Tuscany
      (5482 interviewed patients in 100 clinical directorates). Secondly, we explored
      the association between PLHAMA and mortality at the ward level through
      correlation and regression analyses, using data of 405 wards of eight clinical
      specialties within 24 IRPES university hospitals. RESULTS: Lower PLHAMA rates
      were associated with a higher PS in both regional and clinical directorate
      levels. A positive association between PLHAMA and mortality was shown at the ward
      level for IRPES university hospitals, with different results for medical and
      surgical clinical specialties. CONCLUSIONS: PS is an important performance
      dimension that provides healthcare managers and professionals with useful
      insights for improving care quality and effectiveness. Based on the study
      results, the PLHAMA rate could be regularly measured to highlight patient
      dissatisfaction. Due to the association between PLHAMA and mortality, this study
      also provides evidence of the importance of the patient perspective in assessing
      the quality of healthcare services. This relationship proved to be significant
      for surgical clinical units, suggesting the need for further analysing outcomes
      considering their different determinants in medical and surgical care.

PMID- 29378591
TI  - Chitosan-DNA nanoparticles enhanced the immunogenicity of multivalent DNA
      vaccination on mice against Trueperella pyogenes infection.
AB  - BACKGROUND: Trueperella pyogenes is a commensal and opportunistic pathogen that
      normally causes mastitis, liver abscesses and pneumonia of economically important
      livestock. To develop efficacious and potent vaccine against T. pyogenes,
      chimeric gene DNA vaccines were constructed and encapsulated in chitosan
      nanoparticles (pPCFN-CpG-CS-NPs). RESULTS: The pPCFN-CpG-CS-NPs consists of the
      plo, cbpA, fimA, and nanH gene of T. pyogenes and CpG ODN1826. It was produced
      with good morphology, high stability, a mean diameter of 93.58 nm, and a zeta
      potential of + 5.27 mV. Additionally, chitosan encapsulation was confirmed to
      protect the DNA plasmid from DNase I digestion. The immunofluorescence assay
      indicated that the four-chimeric gene could synchronously express in HEK293T
      cells and maintain good bioactivity. Compared to the mice immunized with the
      control plasmid, in vivo immunization showed that mice immunized with the pPCFN
      CpG-CS-NPs had better immune responses, and release of the plasmid DNA was
      prolonged. Importantly, immunization with pPCFN-CpG-CS-NPs could significantly
      protect mice from highly virulent T. pyogenes TP7 infection. CONCLUSIONS: This
      study indicates that chitosan-DNA nanoparticles are potent immunization
      candidates against T. pyogenes infection and provides strategies for the further
      development of novel vaccines encapsulated in chitosan nanoparticles.

PMID- 29378592
TI  - Sox5 is involved in germ-cell regulation and sex determination in medaka
      following co-option of nested transposable elements.
AB  - BACKGROUND: Sex determination relies on a hierarchically structured network of
      genes, and is one of the most plastic processes in evolution. The evolution of
      sex-determining genes within a network, by neo- or sub-functionalization, also
      requires the regulatory landscape to be rewired to accommodate these novel gene
      functions. We previously showed that in medaka fish, the regulatory landscape of
      the master male-determining gene dmrt1bY underwent a profound rearrangement,
      concomitantly with acquiring a dominant position within the sex-determining
      network. This rewiring was brought about by the exaptation of a transposable
      element (TE) called Izanagi, which is co-opted to act as a silencer to turn off
      the dmrt1bY gene after it performed its function in sex determination. RESULTS:
      We now show that a second TE, Rex1, has been incorporated into Izanagi. The
      insertion of Rex1 brought in a preformed regulatory element for the transcription
      factor Sox5, which here functions in establishing the temporal and cell-type
      specific expression pattern of dmrt1bY. Mutant analysis demonstrates the
      importance of Sox5 in the gonadal development of medaka, and possibly in mice, in
      a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female
      to-male sex reversal. CONCLUSIONS: Our work reveals an unexpected complexity in
      TE-mediated transcriptional rewiring, with the exaptation of a second TE into a
      network already rewired by a TE. We also show a dual role for Sox5 during sex
      determination: first, as an evolutionarily conserved regulator of germ-cell
      number in medaka, and second, by de novo regulation of dmrt1 transcriptional
      activity during primary sex determination due to exaptation of the Rex1
      transposable element.

PMID- 29378593
TI  - Facile assembly of upconversion nanoparticle-based micelles for active targeted
      dual-mode imaging in pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer remains the leading cause of cancer-related deaths,
      the existence of cancer stem cells and lack of highly efficient early detection
      may account for the poor survival rate. Gadolinium ion-doped upconversion
      nanoparticles (UCNPs) provide opportunities for combining fluorescent with
      magnetic resonance imaging, and they can improve the diagnostic efficacy of early
      pancreatic cancer. In addition, as one transmembrane glycoprotein overexpressed
      on the pancreatic cancer stem cells, CD326 may act as a promising target. In this
      study, we developed a facile strategy for developing anti-human CD326-grafted
      UCNPs-based micelles and performed the corresponding characterizations. After
      conducting in vitro and vivo toxicology experiments, we also examined the active
      targeting capability of the micelles upon dual-mode imaging in vivo. RESULTS: We
      found that the micelles owned superior imaging properties and long-time stability
      based on multiple characterizations. By performing in vitro and vivo toxicology
      assay, the micelles had good biocompatibility. We observed more cellular uptake
      of the micelles with the help of anti-human CD326 grafted onto the micelles.
      Furthermore, we successfully concluded that CD326-conjugated micelles endowed
      promising active targeting ability by conducting dual-mode imaging in human
      pancreatic cancer xenograft mouse model. CONCLUSIONS: With good biocompatibility
      and excellent imaging properties of the micelles, our results uncover efficient
      active homing of those micelles after intravenous injection, and undoubtedly
      demonstrate the as-obtained micelles holds great potential for early pancreatic
      cancer diagnosis in the future and would pave the way for the following
      biomedical applications.

PMID- 29378594
TI  - Decreased endemic malaria in Suriname: moving towards elimination.
AB  - BACKGROUND: Suriname has moved from being the country with the highest annual
      parasite index in the Americas to one on the threshold of elimination. The
      progress toward elimination in the stable populations of Suriname between 2000
      and 2015 is reviewed. METHODS: Data was obtained from the Medical Mission and the
      Ministry of Health Malaria Programme case-reporting systems, and analysed with a
      focus on disease burden and differentiation of the disease geographically, by
      malaria species, age, gender, ethnicity, incidence and gametocytaemia. RESULTS:
      Between 2000 and 2015 there were 57,811 locally acquired cases of malaria in the
      stable populations of Suriname. A significant reduction in indigenous malaria
      cases was observed from 2006 to 2015. The number of imported malaria cases saw a
      relative increase compared to the number of autochthonous cases. In 2015 over 95%
      of the cases reported in stable communities are imported, mainly from
      neighbouring French Guiana, a department of France. The overall decline in
      malaria case incidence followed the mass-distribution of free long-lasting
      insecticide-impregnated mosquito nets and increased awareness building efforts,
      improved access to malaria services as a result of the introduction of Rapid
      Diagnostic Tests and the implementation of active case detection in high risk
      areas. In addition, improved management of Plasmodium falciparum infections was
      achieved with the introduction of artemisinin combination therapy. CONCLUSIONS:
      The existence of a network of policlinics in the interior ran by Medical Mission,
      for the indigenous population, allowed the rapid implementation of the strategy
      in stable communities. The success of malaria control in Suriname indicates that
      the availability at local level, of prompt and adequate prevention, diagnosis and
      treatment is a key requirement for the elimination of malaria.

PMID- 29378595
TI  - HIV evolution and diversity in ART-treated patients.
AB  - Characterizing HIV genetic diversity and evolution during antiretroviral therapy
      (ART) provides insights into the mechanisms that maintain the viral reservoir
      during ART. This review describes common methods used to obtain and analyze intra
      patient HIV sequence data, the accumulation of diversity prior to ART and how it
      is affected by suppressive ART, the debate on viral replication and evolution in
      the presence of ART, HIV compartmentalization across various tissues, and
      mechanisms for the emergence of drug resistance. It also describes how CD4+ T
      cells that were likely infected with latent proviruses prior to initiating
      treatment can proliferate before and during ART, providing a renewable source of
      infected cells despite therapy. Some expanded cell clones carry intact and
      replication-competent proviruses with a small fraction of the clonal siblings
      being transcriptionally active and a source for residual viremia on ART. Such
      cells may also be the source for viral rebound after interrupting ART. The
      identical viral sequences observed for many years in both the plasma and infected
      cells of patients on long-term ART are likely due to the proliferation of
      infected cells both prior to and during treatment. Studies on HIV diversity may
      reveal targets that can be exploited in efforts to eradicate or control the
      infection without ART.

PMID- 29378597
TI  - Full genome characterization of porcine circovirus type 3 isolates reveals the
      existence of two distinct groups of virus strains.
AB  - BACKGROUND: The occurrence of the novel porcine circovirus type 3 (PCV3) was
      reported from the Americas, Asia and Europe. Although this virus was detected in
      association with various clinical syndromes in pigs, its role as possible swine
      pathogen remains unclear. PCV3 was detected with high prevalence in Polish farms,
      but to date no genome sequences were available from European PCV3 strains.
      METHODS: We collected 1060 serum samples from piglets at the age of 20-24 weeks
      from 53 farms distributed all over Germany. PCV3 DNA was detected using a real
      time PCR and subsequently complete PCV3 genome sequences were obtained after
      multiply primed rolling circle amplification and sequencing of overlapping PCR
      products. Phylogenetic analysis was performed by neighbor-joining method and
      maximum likelihood method. RESULTS: We obtained 15 complete PCV3 genome sequences
      as well as nine partial sequences including the putative ORFs 1, 2 and 3 from
      PCV3 viremic animals in German pig farms. Phylogenetic analysis of these German
      as well as 30 full genome sequences received from GenBank divided the PCV3
      strains into two main groups and several subclusters. Furthermore, we were able
      to define group specific amino acid patterns in open reading frame 1 and 2.
      CONCLUSION: PCV3 is distributed with high prevalence in German pig industry.
      Phylogenetic analysis revealed two clearly separated groups of PCV3 strains,
      which might be considered as PCV3 genotypes. Specific nucleotide and amino acid
      marker positions may serve for easy and fast intraspecies classification and
      genotyping of PCV3 strains. No correlation between PCV3 variants with their
      geographical origin was evident. We found the same diversity of PCV3 strains in
      Germany as in other countries. We hypothesize that PCV3 is not a newly emerging
      virus in the German pig population. Future studies will have to show, if PCV3
      genotype specific biological properties are evident.

PMID- 29378596
TI  - Myeloid-derived suppressor cells in transplantation: the dawn of cell therapy.
AB  - Myeloid-derived suppressor cells (MDSCs) are a series of innate cells that play a
      significant role in inhibiting T cell-related responses. This heterogeneous
      population of immature cells is involved in tumor immunity. Recently, the
      function and importance of MDSCs in transplantation have garnered the attention
      of scientists and have become an important focus of transplantation immunology
      research because MDSCs play a key role in establishing immune tolerance in
      transplantation. In this review, we summarize recent studies of MDSCs in
      different types of transplantation. We also focus on the influence of
      immunosuppressive drugs on MDSCs as well as future obstacles and research
      directions in this field.

PMID- 29378598
TI  - Video pulse rate variability analysis in stationary and motion conditions.
AB  - BACKGROUND: In the last few years, some studies have measured heart rate (HR) or
      heart rate variability (HRV) parameters using a video camera. This technique
      focuses on the measurement of the small changes in skin colour caused by blood
      perfusion. To date, most of these works have obtained HRV parameters in
      stationary conditions, and there are practically no studies that obtain these
      parameters in motion scenarios and by conducting an in-depth statistical
      analysis. METHODS: In this study, a video pulse rate variability (PRV) analysis
      is conducted by measuring the pulse-to-pulse (PP) intervals in stationary and
      motion conditions. Firstly, given the importance of the sampling rate in a PRV
      analysis and the low frame rate of commercial cameras, we carried out an analysis
      of two models to evaluate their performance in the measurements. We propose a
      selective tracking method using the Viola-Jones and KLT algorithms, with the aim
      of carrying out a robust video PRV analysis in stationary and motion conditions.
      Data and results of the proposed method are contrasted with those reported in the
      state of the art. RESULTS: The webcam achieved better results in the performance
      analysis of video cameras. In stationary conditions, high correlation values were
      obtained in PRV parameters with results above 0.9. The PP time series achieved an
      RMSE (mean +/- standard deviation) of 19.45 +/- 5.52 ms (1.70 +/- 0.75 bpm). In
      the motion analysis, most of the PRV parameters also achieved good correlation
      results, but with lower values as regards stationary conditions. The PP time
      series presented an RMSE of 21.56 +/- 6.41 ms (1.79 +/- 0.63 bpm). CONCLUSIONS:
      The statistical analysis showed good agreement between the reference system and
      the proposed method. In stationary conditions, the results of PRV parameters were
      improved by our method in comparison with data reported in related works. An
      overall comparative analysis of PRV parameters in motion conditions was more
      limited due to the lack of studies or studies containing insufficient data
      analysis. Based on the results, the proposed method could provide a low-cost,
      contactless and reliable alternative for measuring HR or PRV parameters in non
      clinical environments.

PMID- 29378599
TI  - miR-3928v is induced by HBx via NF-kappaB/EGR1 and contributes to hepatocellular
      carcinoma malignancy by down-regulating VDAC3.
AB  - BACKGROUND: Hepatitis B virus (HBV) plays a critical role in the tumorigenic
      behavior of human hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been
      reported to participate in HCC development via the regulation of their target
      genes. However, HBV-modulated miRNAs involved in tumorigenesis remain to be
      identified. Here, we found that a novel highly expressed miRNA, TLRC-m0008_3p
      (miR-3928v), may be an important factor that promotes the malignancy of HBV
      related HCC. METHODS: Solexa sequencing was applied to profile miRNAs, and RT
      qPCR was used to identify and quantitate miRNAs. We studied miR-3928v function in
      HCC cell lines by MTT, colony formation, migration/invasion, and vascular mimicry
      (VM) assays in vitro and by a xenograft tumor model in vivo. Finally, we
      predicted and verified the target gene of miR-3928v by a reporter assay, studied
      the function of this target gene, and cloned the promoter of miR-3928v and the
      transcription factor for use in dual-luciferase reporter assays and EMSAs.
      RESULTS: A variant of miR-3928 (miR-3928v) was identified and found to be highly
      expressed in HBV (+) HCC tissues. Voltage-dependent anion channel 3 (VDAC3) was
      validated as a target of miR-3928v and found to mediate the effects of miR-3928v
      in promoting HCC growth and migration/invasion. Furthermore, HBx protein
      increased early growth response 1 (EGR1) expression and facilitated its
      translocation into the nucleus to enhance miR-3928v promoter activity in an NF
      kappaB signaling-dependent manner. CONCLUSIONS: miR-3928v is induced by HBx
      through the NF-kappaB/EGR1 signaling pathway and down-regulates the tumor
      suppressor gene VDAC3 to accelerate the progression of HCC.

PMID- 29378601
TI  - Tissue expression of retinoic acid receptor alpha and CRABP2 in metastatic
      nephroblastomas.
AB  - BACKGROUND: Nephroblastoma or Wilms tumor is the most frequent kidney cancer in
      children and accounts for 98% of kidney tumors in this age group. Despite
      favorable prognosis, a subgroup of these patients progresses to recurrence and
      death. The retinoic acid (RA) pathway plays a role in the chemoprevention and
      treatment of tumors due to its effects on cell differentiation and its
      antiproliferative, anti-oxidant, and pro-apoptotic activities. Reports describe
      abnormal cellular retinoic acid-binding protein 2 (CRABP2) expression in
      neoplasms and its correlation with prognostic factors and clinical and
      pathological characteristics. The aim of this study was to evaluate the
      immunohistochemical expression of retinoic acid receptor alpha (RARA) and CRABP2
      in paraffin-embedded samples of nephroblastomas via semiquantitative and
      quantitative analyses and to correlate this expression with prognostic factors.
      METHODS: Seventy-seven cases of nephroblastomas were selected from pediatric
      oncology services. The respective medical records and surgical specimens were
      reviewed. Three representative tumor samples and one non-tumor renal tissue
      sample were selected for the preparation of tissue microarrays (TMA). The Allred
      scoring system was used for semiquantitative immunohistochemical analyses,
      whereas a morphometric analysis of the stained area was employed for quantitative
      evaluation. The nonparametric Mann-Whitney test was used for comparisons between
      two groups, while the nonparametric Kruskal-Wallis test was used to compare three
      or more groups. RESULTS: Immunopositivity for RARA and CRABP2 was observed in
      both the nucleus and cytoplasm. All histological components of the nephroblastoma
      (blastema, epithelium, and stroma) were positive for both markers. RARA, based on
      semiquantitative analyses, and CRABP2, bases on quantitative analyses, exhibited
      increased immunohistochemical expression in patients with metastasis, with p
      values of 0.0247 and 0.0128, respectively. These findings were similar to the
      results of the quantitative analysis of RARA expression, showing greater
      immunopositivity in tumor samples of patients subjected to pre-surgical
      chemotherapy. No significant correlation was found with the other variables
      studied, such as disease stage, anaplasia, risk group, histological type, nodal
      involvement, and clinical evolution. CONCLUSIONS: Semiquantitative and
      quantitative analyses of the markers RARA and CRABP2 indicate their potential as
      biomarkers for tumor progression and their participation in nephroblastoma
      tumorigenesis.

PMID- 29378600
TI  - Digital PCR as a tool to measure HIV persistence.
AB  - Although antiretroviral therapy is able to suppress HIV replication in infected
      patients, the virus persists and rebounds when treatment is stopped. In order to
      find a cure that can eradicate the latent reservoir, one must be able to quantify
      the persisting virus. Traditionally, HIV persistence studies have used real-time
      PCR (qPCR) to measure the viral reservoir represented by HIV DNA and RNA. Most
      recently, digital PCR is gaining popularity as a novel approach to nucleic acid
      quantification as it allows for absolute target quantification. Various
      commercial digital PCR platforms are nowadays available that implement the
      principle of digital PCR, of which Bio-Rad's QX200 ddPCR is currently the most
      used platform in HIV research. Quantification of HIV by digital PCR is proving to
      be a valuable improvement over qPCR as it is argued to have a higher robustness
      to mismatches between the primers-probe set and heterogeneous HIV, and forfeits
      the need for a standard curve, both of which are known to complicate reliable
      quantification. However, currently available digital PCR platforms occasionally
      struggle with unexplained false-positive partitions, and reliable segregation
      between positive and negative droplets remains disputed. Future developments and
      advancements of the digital PCR technology are promising to aid in the accurate
      quantification and characterization of the persistent HIV reservoir.

PMID- 29378602
TI  - A 3-year follow-up study after treatment with simeprevir in combination with
      pegylated interferon-alpha and ribavirin for chronic hepatitis C virus infection.
AB  - BACKGROUND: Simeprevir is approved with pegylated interferon and ribavirin (PR)
      for chronic hepatitis C virus (HCV) genotype (GT) 1 and GT4 infection in the USA
      and the European Union. METHODS: This 3-year follow-up study assessed the
      durability of sustained virologic response (SVR) (undetectable HCV RNA 12 or 24
      weeks after treatment end), and evaluated the persistence of treatment-emergent
      NS3/4A protease inhibitor resistance in patients not achieving SVR following
      treatment with simeprevir plus PR in the parent study. The maintenance of SVR
      after the last post-therapy follow-up visit of the parent study (LPVPS) was
      assessed using HCV RNA measurements. The persistence of treatment-emergent NS3
      amino acid substitutions in patients with no SVR at LPVPS was assessed using
      population sequencing. No study medications were administered. RESULTS: Overall,
      249 patients were enrolled (200 with SVR at LPVPS; 49 with no SVR at LPVPS); 40
      patients discontinued prematurely (18 with SVR; 22 with no SVR). All 200 enrolled
      patients who achieved SVR in the parent study maintained SVR until the last
      available visit in this study (median follow-up time: 35.8 months). The treatment
      emergent NS3 amino acid substitutions detected at time of failure in the parent
      study in 43/49 enrolled patients were no longer detected in 37/43 (86.0%) at the
      end of this study (median follow-up time: 179.9 weeks [41.3 months]). CONCLUSION:
      This 3-year follow-up study provides evidence for the long-term durability of SVR
      (100%) after successful treatment with simeprevir plus PR. Treatment-emergent NS3
      amino acid substitutions became undetectable in the majority of patients. TRIAL
      REGISTRATION: NCT01349465; ClinicalTrials.gov .

PMID- 29378604
TI  - Splenic hamartoma with bizarre stromal cells: a case report and literature
      review.
AB  - BACKGROUND: Splenic hamartoma is a rare benign vascular proliferative lesion
      composed of unorganized sinusoid-like channels lined with plump or flat
      endothelial cells and characterized by a CD8-positive immunophenotype of the
      lining cells. Scattered bizarre stromal cells can be found in some splenic
      hamartomas. The presence of splenic hamartoma with bizarre stromal cells is
      extremely rare and these bizarre cells make it possible to be regarded as a
      malignancy. Recognition of this rare histologic variant will help to avoid
      diagnostic confusion and overtreatment of this benign entity. CASE PRESENTATION:
      We report a case of a 40-year-old man with occasional left-sided waist back pain.
      A splenic space-occupying lesion was detected by ultrasound and magnetic
      resonance imaging. Microscopically bizarre large cells were scattered throughout
      the splenic hamartoma. The cells exhibited atypical nuclei, scarcely visible
      cytoplasm, and vesicular chromatin, and they did not form expansile clusters and
      lacked mitotic activity. An immunohistochemical panel was performed. The bizarre
      cells strongly expressed vimentin, and the Ki-67 index was very low. The lesion
      was diagnosed as a splenic hamartoma with bizarre stromal cells. CONCLUSIONS: To
      the best of our knowledge, this is the first systematic review on a splenic
      hamartoma with bizarre stromal cells; only six cases have been described in the
      literature. Proper identification is important to secure adequate treatment.

PMID- 29378603
TI  - Additional radiotherapy following endoscopic submucosal dissection for T1a-MM/T1b
      SM esophageal squamous cell carcinoma improves locoregional control.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) can be used as a less invasive
      treatment option for superficial esophageal cancer involving the muscularis
      mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment
      after ESD is needed to prevent lymph node metastasis. However, the efficacy of
      radiotherapy following ESD has not been well evaluated. Moreover, the clinical
      outcomes of patients with large mucosal defects of the esophagus who received
      radiotherapy after ESD have not been reported. This study aimed to clarify the
      efficacy of additional radiotherapy following ESD for esophageal squamous cell
      cancer involving T1a-MM or T1b-SM1. METHODS: We analyzed twenty-seven patients
      with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer
      treated by ESD. Thirteen patients received additional radiotherapy (RT group),
      and the remaining patients did not (non-RT group). Locoregional control (LRC),
      overall survival, cause-specific survival, and adverse events including treatment
      related esophageal strictures were evaluated. RESULTS: The three-year LRC was
      significantly better for the RT than the non-RT group (100% vs. 57.8%,
      respectively; p = 0.022). Chemotherapy following ESD did not improve LRC.
      Multivariate analysis showed that radiotherapy was an independent prognostic
      factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and
      cause-specific survival were not significantly different between the RT and non
      RT groups. A subgroup analysis of patients with mucosal defects involving >= 3/4
      of the esophageal circumference after ESD showed that LRC of the RT group was
      better than that of the non-RT group (p = 0.049). Treatment-related esophageal
      strictures were observed in 2 of 6 patients in the RT group with large mucosal
      defects after ESD. No patients with mucosal defects involving less than 3/4 of
      the circumference after ESD developed treatment-related strictures. CONCLUSIONS:
      Radiotherapy after ESD contributed to better LRC in esophageal squamous cell
      cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in
      some patients with large mucosal defects after ESD. Despite leading to better
      LRC, radiotherapy after ESD should be undertaken after careful consideration for
      patients with large mucosal defects after ESD.

PMID- 29378606
TI  - Treponema pallidum Immunohistochemistry is positive in human intestinal
      Spirochetosis.
AB  - BACKGROUND: Human intestinal spirochetosis (IS) has been recognized for decades,
      but whether it represents commensalism or a pathogenic process remains
      controversial. IS is diagnosed on routine stains with confirmation by silver
      stains but these stains are labor intensive and slow to read. We evaluated the
      Treponema pallidum immunostain as a diagnostic adjunct for IS. METHODS: We
      retrieved biopsies from 33 patients with IS for this study. Each case was tested
      by Warthin-Starry (WS) and T. pallidum immunohistochemistry (IHC). Species
      specific genotyping was performed in 3 cases. RESULTS: Patients with IS ranged
      from 22 to 82 years without gender predilection. IS involved normal (n = 15), and
      inflamed (n = 5) mucosa and colonic polyps (n = 13). Warthin-Starry and T.
      pallidum IHC were positive in all cases including both species of Brachyspira.
      Six (18%) symptomatic patients were treated for IS, and experienced resolution.
      In patients diagnosed with incidental IS on cancer screening (n = 5), follow up
      biopsies, without therapy, were negative for IS. T. pallidum IHC required 75 min
      less hands-on time than WS for performance and was faster to interpret.
      CONCLUSIONS: T. pallidum IHC can be used to confirm the diagnosis of IS and is
      easier to perform and faster to interpret than WS.

PMID- 29378605
TI  - Piperine ameliorates SCA17 neuropathology by reducing ER stress.
AB  - BACKGROUND: Spinocerebellar ataxia 17 (SCA17) belongs to the family of
      neurodegenerative diseases caused by polyglutamine (polyQ) expansion. In SCA17,
      polyQ expansion occurs in the TATA box binding protein (TBP) and leads to the
      misfolding of TBP and the preferential degeneration in the cerebellar Purkinje
      neurons. Currently there is no effective treatment for SCA17. Mesencephalic
      astrocyte-derived neurotrophic factor (MANF) is a recently identified
      neurotrophic factor, and increasing MANF expression ameliorated SCA17
      neuropathology in TBP-105Q knock-in (KI) mouse model, indicating that MANF could
      be a therapeutic target for treating SCA17. METHODS: In this study, we screened a
      collection of 2000 FDA-approved chemicals using a stable cell line expressing
      luciferase reporter, which is driven by MANF promoter. We identified several
      potential candidates that can induce the expression of MANF. Of these inducers,
      piperine is an agent that potently induces the luciferase expression or MANF
      expression. RESULTS: Addition of piperine in both cellular and mouse models of
      SCA17 alleviated toxicity caused by mutant TBP. Although mutant TBP is primarily
      localized in the nuclei, the polyQ expansion in TBP is able to induce ER stress,
      suggesting that nuclear misfolded proteins can also elicit ER stress as
      cytoplasmic misfolded proteins do. Moreover, piperine plays its protective role
      by reducing toxicity caused by the ER stress. CONCLUSION: Our study established
      piperine as a MANF-based therapeutic agent for ER stress-related neuropathology
      in SCA17.

PMID- 29378607
TI  - Development of a rapid point-of-care patient reported outcome measure for
      cataract surgery in India.
AB  - BACKGROUND: For patient undergoing cataract surgery in India, existing patient
      reported outcome (PRO) measures are either not culturally relevant, have not been
      adequately validated, or are too long to be used in a busy clinical setting. We
      sought to develop and validate a brief and culturally relevant point-of-care PRO
      measure to address this need. METHODS: Twelve items from the Indian Visual
      Functioning Questionnaire (IND-VFQ) were selected based on preliminary data.
      Patients 18 years and older were prospectively recruited at Aravind Eye Care
      System in Madurai, India. Clinical and sociodemographic data were collected and
      the 12-item short-form IND-VFQ (SF-IND-VFQ) was administered pre- and post
      operatively to 225 patients; Factor analysis and Rasch modeling was performed to
      assess its psychometric properties. RESULTS: One item that did not fit a
      unidimensional scale and had poor fit with the Rasch model was eliminated from
      the questionnaire. The remaining 11 items represented a single construct (no
      residual correlations> 0.1) and were largely unaffected by differential item
      functioning. Five items had disordered thresholds resolved by collapsing the
      response scale from four to three categories. The survey had adequate reliability
      (0.80) and good construct (infit range, 0.77-1.29; outfit range, 0.56-1.30) and
      content (item separation index, 5.87 logits) validity. Measurement precision was
      fair (person separation index, 1.97). There was evidence that items were not
      optimally targeted to patients' visual ability (preoperatively, - 1.92 logits;
      overall, - 3.41 logits), though the survey measured a very large effect (Cohen's
      d 1.80). In a subset of patients, the average time to complete the questionnaire
      was 2 min 6.3 s. CONCLUSIONS: The SF-IND-VFQ is a valid, reliable, sensitive, and
      rapidly administered point-of-care PRO measure to assess changes in visual
      functioning in patients undergoing cataract surgery in India.

PMID- 29378608
TI  - Case report: IgG4-related mass-forming thyroiditis accompanied by regional
      lymphadenopathy.
AB  - BACKGROUND: It has been recently accepted that IgG4-related thyroiditis is
      comparable to the Hashimoto and Riedel thyroiditis and Graves disease which are
      rich in IgG4-secreting plasma cells. Many physicians believe that in IgG4-related
      thyroiditis, the thyroid is entirely enlarged and diffusely affected, which is
      similar to conventional thyroiditis, but rarely ever accompanied by
      pseudoneoplastic mass formation as in IgG4-related disease in the other organs.
      This report introduces another pattern of IgG4-related thyroiditis as mass
      forming thyroiditis and presents the occurrence of IgG4-related regional
      lymphadenopathy as an unusual accompanying symptom. CASE PRESENTATION: A 66-year
      old woman presented with an approximately 2.5-cm mass in the right thyroidal lobe
      and regional lymph node swelling, which were preoperatively misinterpreted as
      thyroidal carcinoma. After lobectomy, histological examination was performed,
      revealing that the mass showed dense stromal fibrosis, lymphoplasmacytic
      infiltration, and effacement of thyroid follicles, while the background thyroidal
      tissue seemed to mimic lymphocytic thyroiditis without fibrosis.
      Immunohistochemistry revealed predominance of IgG4-secreting plasma cells among
      infiltrating lymphocytes independent of mass lesion or background tissue. In
      addition, the regional Delphian and paratracheal lymph nodes were swollen,
      histologically showing numerous IgG4-secreting plasma cell infiltrations in the
      interfollicular zone. CONCLUSIONS: IgG4-related mass-forming thyroiditis, which
      may be an extremely rare but recognizable pattern of IgG4-related thyroiditis,
      may be distinguishable from Hashimoto and Riedel thyroiditis, Graves disease, and
      thyroidal carcinoma. In addition, the regional IgG4-related lymphadenopathy, also
      possibly misdiagnosed as metastatic thyroidal carcinoma, may be a newly
      recognized manifestation of IgG4-related thyroiditis.

PMID- 29378609
TI  - Plasmodium vivax molecular diagnostics in community surveys: pitfalls and
      solutions.
AB  - A distinctive feature of Plasmodium vivax infections is the overall low parasite
      density in peripheral blood. Thus, identifying asymptomatic infected individuals
      in endemic communities requires diagnostic tests with high sensitivity. The
      detection limits of molecular diagnostic tests are primarily defined by the
      volume of blood analysed and by the copy number of the amplified molecular marker
      serving as the template for amplification. By using mitochondrial DNA as the
      multi-copy template, the detection limit can be improved more than tenfold,
      compared to standard 18S rRNA targets, thereby allowing detection of lower
      parasite densities. In a very low transmission area in Brazil, application of a
      mitochondrial DNA-based assay increased prevalence from 4.9 to 6.5%. The
      usefulness of molecular tests in malaria epidemiological studies is widely
      recognized, especially when precise prevalence rates are desired. Of concern,
      however, is the challenge of demonstrating test accuracy and quality control for
      samples with very low parasite densities. In this case, chance effects in
      template distribution around the detection limit constrain reproducibility.
      Rigorous assessment of false positive and false negative test results is,
      therefore, required to prevent over- or under-estimation of parasite prevalence
      in epidemiological studies or when monitoring interventions.

PMID- 29378610
TI  - HyperArc VMAT planning for single and multiple brain metastases stereotactic
      radiosurgery: a new treatment planning approach.
AB  - PURPOSE: The HyperArc VMAT (HA-VMAT) planning approach was newly developed to
      fulfill the demands of dose delivery for brain metastases stereotactic
      radiosurgery. We compared the dosimetric parameters of the HA-VMAT plan with
      those of the conventional VMAT (C-VMAT). MATERIAL AND METHODS: For 23 patients (1
      4 brain metastases), C-VMAT and HA-VMAT plans with a prescription dose of 20-24
      Gy were retrospectively generated, and dosimetric parameters for PTV (homogeneity
      index, HI; conformity index, CI; gradient index, GI) and brain tissue (V2Gy
      V16Gy) were evaluated. Subsequently, the physical characteristics (modulation
      complexity score for VMAT, MCSV; Monitor unit, MU) of both treatment approaches
      were compared. RESULTS: HA-VMAT provided higher HI (1.41 +/- 0.07 vs. 1.24 +/-
      0.07, p < 0.01), CI (0.93 +/- 0.02 vs. 0.90 +/- 0.05, p = 0.01) and lower GI
      (3.06 +/- 0.42 vs. 3.91 +/- 0.55, p < 0.01) values. Moderate-to-low dose spreads
      (V4Gy-V16Gy) were significantly reduced (p < 0.01) in the HA-VMAT plan over that
      of C-VMAT. HA-VMAT plans resulted in more complex MLC patterns (lower MCSV, p <
      0.01) and higher MU (p < 0.01). CONCLUSIONS: HA-VMAT plans provided significantly
      higher conformity and rapid dose falloff with respect to the C-VMAT plans.

PMID- 29378612
TI  - Case report of an unusual combination of purulent pericarditis and false aneurysm
      of the ascending aorta.
AB  - BACKGROUND: Purulent pericarditis is an uncommon entity, which is, in very rare
      cases, associated to infection of the aorta. CASE PRESENTATION: We present the
      case of a 42-year-old male patient, who was admitted to hospital complaining of
      tiredness, diarrhea and leg edema. Clinical examination revealed a hypotensive
      and obviously shocked patient. He was ultimately diagnosed with a rare
      combination of purulent pericarditis followed by false aneurysm of the ascending
      aorta. He was successfully treated by surgical pericardial drainage, replacement
      of the ascending aorta and antibiotics. CONCLUSION: Mycotic aneurysms can rarely
      be associated with purulent pericarditis. Our literature review shows that there
      are two mechanisms explaining this association and that in most of the published
      cases infective endocarditis could not be demonstrated.

PMID- 29378611
TI  - Episomal HIV-1 DNA and its relationship to other markers of HIV-1 persistence.
AB  - Reverse transcription of HIV-1 results in the generation of a linear cDNA that
      serves as the precursor to the integrated provirus. Other classes of
      extrachromosomal viral cDNA molecules can be found in acutely infected cells
      including the 1-LTR and 2-LTR circles of viral DNA, also referred as episomal HIV
      1 DNA. Circulating CD4+ T-cells of treatment-naive individuals contain
      significant levels of unintegrated forms of HIV-1 DNA. However, the importance of
      episomal HIV-1 DNA in the study of viral persistence during antiviral therapy
      (ART) is debatable. 2-LTR circles are preferentially observed in the effector
      memory CD4+ T cell subset of long-term treated subjects. Treatment
      intensification of standard regimens has been used to determine if more potent
      ART can impact viral reservoir activity. Adding a potent antiretroviral drug to a
      stable triple-drug regimen has no measurable impact on plasma HIV-1 RNA levels,
      suggesting that ongoing cycles of HIV-1 replication are not a major mechanism
      driving persistent plasma viremia during triple-drug ART. However, in randomized
      clinical trials of HIV-1-infected adults on apparently effective ART, the
      addition of an integrase inhibitor (raltegravir) to stable regimens resulted in a
      transient increase in 2-LTR circles in some patients, suggesting a pre
      intensification steady-state in which the processes of virion generation and de
      novo infection were occurring. Mathematical modeling of 2-LTR production during
      integrase inhibitor intensification suggests the coexistence, at different
      levels, of ongoing de novo infection and de novo replication mechanisms,
      specifically in inflamed lymphoid drug sanctuaries. Most reports looking into
      potential changes in 2-LTR circles in interventional clinical studies have
      simultaneously assessed other potential surrogate markers of viral persistence.
      Transient increases in 2-LTR circles have been correlated to decreases in CD8+ T
      cell activation, transient CD45RA-CD4+ T-cell redistribution, and decreases in
      the hypercoagulation biomarker D-dimer in ART-intensified individuals. It is
      difficult, however, to establish a systematic association because the level of
      correlation with different types of markers differs significantly among studies.
      In conclusion, despite suppressive ART, a steady-state of de novo infection may
      persist in some infected individuals and that this may drive immune activation
      and inflammation changes reflecting residual viral reservoir activity during
      otherwise apparently suppressive ART.

PMID- 29378613
TI  - Axial loading during MRI induces significant T2 value changes in vertebral
      endplates-a feasibility study on patients with low back pain.
AB  - BACKGROUND: The function of the endplate (EP) is the most important factor
      influencing nutritional supply to the avascular intervertebral disc (IVD). It is
      desired to have a non-invasive method to assess functional EP characteristics in
      vivo. Assessment of functional EP characteristics is important in order to
      understand its relation to IVD degeneration, which in turn might deepen the
      understanding of the pathophysiology behind low back pain (LBP). It was
      hypothesized that, by comparing quantitative MRI of EPs performed with
      conventional supine MRI (unloaded MRI) with axial loading during MRI (alMRI),
      dynamical properties of the EP can be displayed. The aim was therefore to
      investigate the feasibility of axial loading during MRI (alMRI) to
      instantaneously induce quantitative EP changes. METHODS: T2 mapping of 55
      vertebral EPs (L1-S1) in five LBP patients was performed during conventional
      supine MRI (unloaded MRI) and subsequent alMRI. With T2 mapping, the
      cartilaginous EP and bony EP cannot be separated; hence, the visualized EP was
      termed EP zone (EPZ). Each EPZ was segmented at multiple midsagittal views,
      generating volumetric regions of interest. EPZs demonstrating signal
      inhomogeneity and/or adjacent Modic changes (MC) were termed abnormal EPZs. EPZ
      mean T2 values were compared between unloaded MRI and alMRI, and their
      relationship with abnormal EPZs was determined. RESULTS: alMRI induced
      significantly higher (p = 0.01) EPZ mean T2 values compared with unloaded MRI.
      Significantly higher mean T2 values were seen in inferior EPZs compared with
      superior EPZs, both with unloaded MRI (35%, p < 0.001) and with alMRI (26%, p =
      0.04). Significant difference between unloaded MRI and alMRI was seen in normal
      (p = 0.02), but not in abnormal EPZs (p = 0.5; n = 12). CONCLUSIONS: alMRI
      induces changes in human EPZ characteristics in vivo. The T2 value significantly
      increased in normal EPZs, with lack of such in abnormal EPZs. Combining T2
      mapping with alMRI provides a clinical feasible, non-invasive method with
      potential to reveal biochemical behavioral patterns, thus adding another
      dimension of the EPZs characteristics compared with information obtained with
      solely unloaded MRI.

PMID- 29378614
TI  - Diversity and use of wild and non-cultivated edible plants in the Western
      Himalaya.
AB  - BACKGROUND: Local people in the Himalayan region use a wide range of wild and non
      cultivated edible plants (WNEPs) for food, spice, medicinal, and cultural
      purposes. However, their availability, use, status and contribution to livelihood
      security are poorly documented, and they have been generally overlooked in recent
      agro-biodiversity conservation and management programmes. The study aimed to
      investigate WNEP diversity and current status in a part of the Kailash Sacred
      Landscape-a transboundary landscape shared by Nepal, India and PR China-in terms
      of collection, use, management and conservation initiatives. METHODS: Multiple
      methodologies and tools were used for data collection. A series of participatory
      tools (45 key informant interviews, 10 focus group discussions, a crop diversity
      fair, direct observation of species through a transect walk and rapid market
      assessments) was followed by a household survey (195 respondents) and
      complemented by a literature review. RESULTS: The study recorded 99 WNEPs
      belonging to 59 families of which 96 were angiosperms, one gymnosperm and two
      pteridophytes. Species were used for food, spice, medicine, rituals and income
      generation. Thirty-five species had multiple uses, including these: 40 species
      were used for fruit and 31 for vegetables. WNEPs contribute significantly to
      daily food requirements, especially the vegetables. The use value of Dryopteris
      cochleata was found highest (0.98) among frequently used vegetable species. The
      values of informant consensus factor were found maximum for worms in the stomach
      (0.99) and minimum for skin disease treatment (0.67). Nearly 85% of households
      depended exclusively on WNEPs for at least more than a month per year. Results on
      the importance and use of different species, gender roles in WNEP activities and
      conservation approaches are presented. CONCLUSIONS: People living in the Kailash
      Sacred Landscape depend significantly on WNEPs, and this is especially critical
      in times of food shortage. The WNEPs have considerable potential as an important
      supplement to cultivated food crops. Farmers prioritise species with multiple use
      values and popular vegetables. However, there are numerous challenges and
      interventions needed to ensure conservation and management of species and their
      continued availability to support food security and local livelihoods.

PMID- 29378615
TI  - Expression of cystatin C in the female reproductive tract and its effect on human
      sperm capacitation.
AB  - BACKGROUND: Cystatin C (CST3), a cysteine protease inhibitor in seminal plasma,
      is expressed in animal uteri. However, its expression in the human female
      reproductive tract and its effect on human sperm capacitation are unclear.
      METHODS: The cellular localization of CST3 was observed using
      immunohistochemistry. The binding of CST3 to sperm was examined using
      immunocytochemistry. Sperm motility parameters were analyzed using computer
      assisted sperm analysis. Sperm capacitation was evaluated by analyzing
      cholesterol content, protein tyrosine phosphorylation levels, and the acrosome
      reaction. RESULTS: Immunohistochemical staining demonstrated that CST3 is
      prominently expressed in the female reproductive tract, including the epithelial
      lining and cervix and endometrium fluids, particularly at times near ovulation.
      It can bind to human sperm on the post-acrosomal head region and the mid and
      principal piece of the tail. CST3 enhances sperm motility and inhibits the signal
      initiating sperm capacitation, i.e., efflux of cholesterol from the sperm plasma
      membrane and a late sperm capacitation event, i.e., the increase in the sperm
      protein tyrosine phosphorylation. The suppressive trend on sperm acrosome
      reaction further supports CST3's ability to inhibit sperm capacitation.
      CONCLUSIONS: These findings suggest that cervical CST3 may prevent precocious
      capacitation and acrosome reaction, thus preserving sperm fertilizing ability
      before it reaches the fallopian tube. Additionally, CST3 may help sperm enter the
      upper reproductive tract by enhancing sperm motility.

PMID- 29378616
TI  - Sensemaking in the formation of basic life support teams - a proof-of-concept,
      qualitative study of simulated in-hospital cardiac arrests.
AB  - BACKGROUND: The formation of critical care teams is a complex process where team
      members need to get a shared understanding of a serious situation. No previous
      studies have focused on how this shared understanding is achieved during the
      formation of cardiac arrest teams. "Sensemaking" is a concept well known in
      organizational studies. It refers to the collaborative effort among members in a
      dialogue to create meaning in an ambiguous situation, often by using subtle
      variations in the sentences in the dialogue. Sentences with high degrees of
      "sensemaking" activity can be thematized as "co-orientation", "re-presentation"
      and/or "subordination" (among others). We sought to establish if elements of
      "sensemaking" occur in the formation of in-hospital cardiac arrest teams.
      METHODS: Videos of ten simulations of unannounced in-hospital cardiac arrests
      treated by basic life support (BLS) providers. We transcribed all verbal
      communication from the moment the first responder stepped into the room until the
      moment external chest compression were initiated (verbatim transcription).
      Transcriptions were then analyzed with a focus on identifying three elements of
      sensemaking: Co-orientation, Re-presentation and Sub-ordination. RESULTS:
      Sensemaking elements could be identified in seven of ten scenarios as part of
      team formation. Co-orientation was the element that was used most consistently,
      occurring in all of the eight scenarios that included sensemaking efforts.
      CONCLUSIONS: Sensemaking is an element in the communication in some cardiac
      arrest teams. It is possible that the active moderation of sensemaking should be
      considered a non-technical skill in cardiac arrest teams.

PMID- 29378617
TI  - PD-L1 in pancreatic ductal adenocarcinoma: a retrospective analysis of 373
      Chinese patients using an in vitro diagnostic assay.
AB  - BACKGROUND: Programmed death ligand 1 (PD-L1) has shown potential as a
      therapeutic target in numerous solid tumors. Its prognostic significance has also
      been established in pancreatic ductal adenocarcinoma (PDAC). The present study
      aimed to explore PD-L1 expression in PDAC cases in a large Chinese cohort using
      an in vitro diagnostic (IVD) assay to provide further insight into the potential
      value of programmed cell death protein 1 (PD-1) as a therapeutic target. METHODS:
      Three hundred seventy-three PDAC patients were retrospectively recruited in this
      study. Tissue microarray (TMA) blocks were made from available formalin-fixed and
      paraffin-embedded (FFPE) tumor and matched adjacent tissue specimens. We
      evaluated PD-L1 protein expression via immunohistochemistry (IHC) using a U.S.
      Food and Drug Administration (FDA)-approved IVD assay. The relationships between
      PD-L1 positivity and both clinicopathological characteristics and patient
      prognosis were analyzed. PD-1 expression and clinicopathological significance
      were also evaluated. RESULTS: PD-L1 and PD-1 positivity were observed in 3.2% and
      7.5% of cases, respectively. PD-L1 showed a predominantly membranous pattern in
      tumor cells, while no positive PD-L1 staining was observed in normal regions.
      Statistical analyses revealed that PD-L1 expression was associated with lymph
      node metastasis. PD-L1 positivity was a prognostic indicator of progression-free
      survival (PFS) and overall survival (OS) in univariate analyses, but only PFS
      remained statistically significant in multivariate analysis. PD-1 expression was
      detected in lymphocytes and was not associated with any clinicopathological
      feature except a history of pancreatitis. CONCLUSIONS: The PD-L1 positivity rate
      is low in PDAC when evaluated using a companion diagnostic assay. It remains an
      independent prognostic factor for poor PFS.

PMID- 29378618
TI  - 'Recruitment, recruitment, recruitment' - the need for more focus on retention: a
      qualitative study of five trials.
AB  - BACKGROUND: Loss to follow-up (attrition) is a frequent problem in clinical
      trials and can introduce bias or reduce power. So, understanding retention issues
      and strategies to address these are important. As part of a multi-method project,
      this qualitative study aimed to explore retention strategies used by trial teams
      and factors which may influence strategy adoption. METHOD: A purposive sample of
      active trials was selected from the UK NIHR HTA portfolio of ongoing trials in
      2014/2015. Semi-structured interviews with several trial team members from each
      trial and supplementary interviews with experienced trial managers explored
      strategies in collecting clinical outcome data and retaining participants.
      Interview data were analysed thematically using techniques of constant
      comparison. RESULTS: Twenty-two semi-structured interviews with trial team
      members including chief investigators, trial managers, nurses and research
      administrators revealed strategies used to enhance retention. Some were
      recognised methods and planned from trial outset whilst others were implemented
      more responsively. Interviewees placed great value on fostering positive
      relationships with trial participants to enhance retention. However, these
      strategies took time which was not always appreciated by the wider trial team or
      funding bodies. The national focus on recruitment targets in networks posed a
      challenge to staff and was deemed detrimental to retention. The 'moral compass'
      of individual researchers relied on their own beliefs and values and research
      experience and the factors affected their confidence to pursue participant data
      during follow-up. CONCLUSION: The role of trial staff and their underlying
      behaviours influence retention practices and, combined with emphasis on
      recruitment targets, can be detrimental to motivation and retention activities.
      There is a need to consider how to train and support trial staff involved in
      retention practices and recognition of retention from funding bodies and
      oversight organisations.

PMID- 29378620
TI  - Human infection with sub-periodic Brugia spp. in Gampaha District, Sri Lanka: a
      threat to filariasis elimination status?
AB  - BACKGROUND: Post-mass drug administration (MDA) surveillance during the lymphatic
      filariasis (LF) elimination program in Sri Lanka, revealed the re-emergence of
      brugian filariasis after four decades. This study was done with the objectives of
      investigating the epidemiology and age-specific vulnerability to infection.
      Surveillance was done using night blood smears (NBS) and the Brugia rapid test
      (BRT), to detect microfilaria (MF) and anti-Brugia IgG4 antibodies in blood
      samples collected from an age-stratified population enrolled from two high-risk
      study areas (SA)s, Pubudugama and Wedamulla in the Gampaha District. The
      periodicity of the re-emergent Brugia spp. was characterized by quantitative
      estimation of MF in blood collected periodically over 24 h using nucleopore
      membrane filtration method. RESULTS: Of 994 participants [Pubudugama 467 (47.9%)
      and Wedamulla 527 (53%)] screened by NBS, two and zero cases were positive for MF
      at Pubudugama (MF rate, 0.43) and Wedamulla (MF rate, 0), respectively, with an
      overall MF rate of 0.2. Of the two MF positives, one participant had a W.
      bancrofti while the other had a Brugia spp. infection. Of 984 valid BRT test
      readings [Pubudugama (n = 461) and Wedamulla (n = 523)], two and seven were
      positive for anti-brugia antibodies by BRT at Pubudugama (antibody rate 0.43) and
      Wedamulla (antibody rate 1.34), respectively, with an overall antibody rate of
      0.91. Both MF positives detected from SAs and two of three other Brugia spp. MF
      positives detected at routine surveillance by the National Anti-Filariasis
      Campaign (AFC) tested negative by the BRT. Association of Brugia spp. infections
      with age were not evident due to the low case numbers. MF was observed in the
      peripheral circulation throughout the day (subperiodic) with peak counts
      occurring at 21 h indicating nocturnal sub-periodicity. CONCLUSIONS: There is the
      low-level persistence of bancroftian filariasis and re-emergence of brugian
      filariasis in the Gampaha District, Sri Lanka. The periodicity pattern of the re
      emergent Brugia spp. suggests a zoonotic origin, which causes concern as MDA may
      not be an effective strategy for control. The importance of continuing
      surveillance is emphasized in countries that have reached LF elimination targets
      to sustain programmatic gains.

PMID- 29378619
TI  - Chromosome conformation signatures define predictive markers of inadequate
      response to methotrexate in early rheumatoid arthritis.
AB  - BACKGROUND: There is a pressing need in rheumatoid arthritis (RA) to identify
      patients who will not respond to first-line disease-modifying anti-rheumatic
      drugs (DMARD). We explored whether differences in genomic architecture
      represented by a chromosome conformation signature (CCS) in blood taken from
      early RA patients before methotrexate (MTX) treatment could assist in identifying
      non-response to DMARD and, whether there is an association between such a
      signature and RA specific expression quantitative trait loci (eQTL). METHODS: We
      looked for the presence of a CCS in blood from early RA patients commencing MTX
      using chromosome conformation capture by EpiSwitchTM. Using blood samples from
      MTX responders, non-responders and healthy controls, a custom designed biomarker
      discovery array was refined to a 5-marker CCS that could discriminate between
      responders and non-responders to MTX. We cross-validated the predictive power of
      the CCS by generating 150 randomized groups of 59 early RA patients (30
      responders and 29 non-responders) before MTX treatment. The CCS was validated
      using a blinded, independent cohort of 19 early RA patients (9 responders and 10
      non-responders). Last, the loci of the CCS markers were mapped to RA-specific
      eQTL. RESULTS: We identified a 5-marker CCS that could identify, at baseline,
      responders and non-responders to MTX. The CCS consisted of binary chromosome
      conformations in the genomic regions of IFNAR1, IL-21R, IL-23, CXCL13 and IL-17A.
      When tested on a cohort of 59 RA patients, the CCS provided a negative predictive
      value of 90.0% for MTX response. When tested on a blinded independent validation
      cohort of 19 early RA patients, the signature demonstrated a true negative
      response rate of 86 and a 90% sensitivity for detection of non-responders to MTX.
      Only conformations in responders mapped to RA-specific eQTL. CONCLUSIONS: Here we
      demonstrate that detection of a CCS in blood in early RA is able to predict
      inadequate response to MTX with a high degree of accuracy. Our results provide a
      proof of principle that a priori stratification of response to MTX is possible,
      offering a mechanism to provide alternative treatments for non-responders to MTX
      earlier in the course of the disease.

PMID- 29378621
TI  - Novel botanical drug DA-9803 prevents deficits in Alzheimer's mouse models.
AB  - BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder
      characterized by deposition of amyloid plaques and disruption of neural
      circuitry, leading to cognitive decline. Animal models of AD deposit senile
      plaques and exhibit structural and functional deficits in neurons and neural
      networks. An effective treatment would prevent or restore these deficits,
      including calcium dyshomeostasis observed with in-vivo imaging. METHODS: We
      examined the effects of DA-9803, a multimodal botanical drug, in 5XFAD and
      APP/PS1 transgenic mice which underwent daily oral treatment with 30 or 100 mg/kg
      DA-9803 or vehicle alone. Behavioral testing and longitudinal imaging of amyloid
      deposits and intracellular calcium in neurons with multiphoton microscopy was
      performed. RESULTS: Chronic administration of DA-9803 restored behavioral
      deficits in 5XFAD mice and reduced amyloid-beta levels. DA-9803 also prevented
      progressive amyloid plaque deposition in APP/PS1 mice. Elevated calcium, detected
      in a subset of neurons before the treatment, was restored and served as a
      functional indicator of treatment efficacy in addition to the behavioral readout.
      In contrast, mice treated with vehicle alone continued to progressively
      accumulate amyloid plaques and calcium overload. CONCLUSIONS: In summary,
      treatment with DA-9803 prevented structural and functional outcome measures in
      mouse models of AD. Thus, DA-9803 shows promise as a novel therapeutic approach
      for Alzheimer's disease.

PMID- 29378622
TI  - Maximizing adherence and retention for women living with HIV and their infants in
      Kenya (MOTIVATE! study): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Successful completion and retention throughout the multi-step cascade
      of prevention of mother-to-child HIV transmission (PMTCT) remains difficult to
      achieve. The Mother and Infant Visit Adherence and Treatment Engagement study
      aims to evaluate the effect of mobile text messaging, community-based mentor
      mothers (cMMs), or both on increasing antiretroviral therapy (ART) adherence,
      retention in HIV care, maternal viral load suppression, and mother-to-child HIV
      transmission for mother-infant pairs receiving lifelong ART. METHODS/DESIGN: This
      study is a cluster randomized, 2 * 2 factorial, controlled trial. The trial will
      be undertaken in the western Kenyan counties of Migori, Kisumu, and Homa Bay.
      Study sites will be randomized into one of four groups: six sites will implement
      both text messaging and cMM, six sites will implement cMM only, six sites will
      implement text messaging only, and six sites will implement the existing standard
      of care. The primary analysis will be based on the intention-to-treat principle
      and will compare maternal ART adherence and maternal retention in care.
      DISCUSSION: This study will determine the impact of long-term (up to 12 months
      postpartum) text messaging and cMMs on retention in and adherence to ART among
      pregnant and breastfeeding women living with HIV in Kenya. It will address key
      gaps in our understanding of what interventions may successfully promote long
      term retention in the PMTCT cascade of care. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02491177 . Registered on 11 March 2015.

PMID- 29378623
TI  - Patient perspectives of transitioning from prescription opioids to heroin and the
      role of route of administration.
AB  - BACKGROUND: As the availability of prescription opioids decreases and the
      availability of heroin increases, some prescription opioid users are
      transitioning to heroin. This study seeks to explore factors associated with
      respondents' transition from prescription opioid use to heroin. METHODS: In
      depth, semi-structured qualitative interviews (n = 20) were conducted with
      buprenorphine patients in an opioid treatment program. Respondents were
      predominantly White (n = 13) and male (n = 13), with a range of treatment tenure
      (4 days to 2 years). RESULTS: A vast majority of respondents in this study (n =
      15) initiated opioid use with either licit (n = 8) or illicit (n = 7)
      prescription opioids (e.g. hydrocodone, oxycodone, morphine). Of these
      respondents, all but two transitioned from prescription opioids to heroin (n =
      13). For those respondents who transitioned to heroin, most initiated heroin use
      intranasally (n = 12), after using prescription opioids in the same manner (n =
      9), but before using heroin intravenously (n = 9). Respondents attributed this
      transition between substances to common explanations, such as "it's cheaper" and
      "the same thing as pills." However, respondents also dispel these myths by
      describing: 1) heroin quality is always uncertain, often resulting in spending
      more money over time; 2) dramatic increases in tolerance, resulting in spending
      more money over time and transitioning to intravenous use; 3) more severe
      withdrawal symptoms, especially when respondents transitioned to intravenous use.
      CONCLUSIONS: Understanding how route of administration and common myths shape key
      transition points for opioid users will allow practitioners to develop effective
      harm reduction and prevention materials that target individuals already using
      prescription opioids.

PMID- 29378624
TI  - Evaluation of the tumor movement and the reproducibility of two different
      immobilization setups for image-guided stereotactic body radiotherapy of liver
      tumors.
AB  - BACKGROUND: The purpose of this study is to evaluate the tumor movement and
      accuracy of patient immobilization in stereotactic body radiotherapy of liver
      tumors with low pressure foil or abdominal compression. METHODS: Fifty-four liver
      tumors treated with stereotactic body radiotherapy were included in this study.
      Forty patients were immobilized by a vacuum couch with low pressure foil, 14
      patients by abdominal compression. We evaluated the ratio of gross tumor
      volume/internal target volume, the tumor movement in 4D-computed tomography scans
      and daily online adjustments after cone beam computed tomography scans. RESULTS:
      The ratio of gross tumor volume/internal target volume was smaller with low
      pressure foil. The tumor movement in 4D-computed tomography scans was smaller
      with abdominal compression, the cranial movement even significantly different (p
      = 0.02). The mean online adjustments and their mean absolute values in the
      vertical, lateral and longitudinal axis were smaller with abdominal compression.
      The online adjustments were significantly different (p < 0.013), their absolute
      values in case of the longitudinal axis (p = 0.043). There was no significant
      difference of the adjustments' 3D vectors. CONCLUSIONS: In comparison to low
      pressure foil, abdominal compression leads to a reduction of the tumor movement.
      Online adjustments decreased significantly, thus leading to higher accuracy in
      patient positioning.

PMID- 29378625
TI  - Outcome and prognostic factors in cervical cancer patients treated with surgery
      and concurrent chemoradiotherapy: a retrospective study.
AB  - BACKGROUND: The objective of this study is to analyze the treatment outcome and
      secondary reactions in 98 patients with stage I-III cervical carcinoma who
      underwent postoperative radiotherapy. METHODS: From 2006 to 2014, 98 patients
      with stage I-III cervical carcinoma were treated with postoperative radiotherapy.
      The major histological type, found in 92.86% of the patients (91 cases), was
      squamous cell carcinoma. Patients were staged according to the 2002 TNM
      guidelines. The postoperative radiotherapy methods included two-field irradiation
      (16 patients, 16.32%), four-field box irradiation (16 patients, 16.32%), and
      intensity-modulated radiotherapy (IMRT; 66 patients, 67.36%). The survival rates
      were represented using Kaplan-Meier curves, and prognosis analyses were performed
      using Cox multivariate analyses. RESULTS: The 5-year overall survival and
      progression-free survival rates were 82.0 and 76.0%, respectively. Only one
      patient (1.02%) developed a grade 3 acute radiation enteritis, while grade 3 and
      4 myelosuppression was noted in 17 patients (17.35%) and one patient (1.02%),
      respectively. Multivariate analyses showed that anemia before radiotherapy and
      tumor size were predictors of the OS (P = 0.008, P = 0.045) rates. CONCLUSIONS:
      Postoperative radiotherapy for patients with risk factors of cervical cancer
      procured good efficacy levels with mild side effects. Anemia and tumor size were
      important OS predictors.

PMID- 29378626
TI  - Prevalence and molecular characterization of Strongyloides stercoralis, Giardia
      duodenalis, Cryptosporidium spp., and Blastocystis spp. isolates in school
      children in Cubal, Western Angola.
AB  - BACKGROUND: Human infections by the gastrointestinal helminth Strongyloides
      stercoralis and the enteric protozoans Giardia duodenalis, Cryptosporidium spp.
      and Blastocystis spp. are not formally included in the list of 20 neglected
      tropical diseases prioritised by the World Health Organization. Although largely
      underdiagnosed and considered of lower public health relevance, these infections
      have been increasingly demonstrated to cause significant morbidity and even
      mortality globally, particularly among children living in resource-poor settings.
      METHODS: In this cross-sectional survey the prevalence, frequency and molecular
      diversity of S. stercoralis, G. duodenalis, Cryptosporidium spp. and Blastocystis
      spp. were investigated in a school children population in the province of
      Benguela (Angola). A total of 351 stool samples were collected during January to
      June 2015. The presence of S. stercoralis and G. duodenalis was confirmed by qPCR
      methods. Giardia duodenalis assemblages and sub-assemblages were determined by
      multilocus sequence-based genotyping of the glutamate dehydrogenase and beta
      giardin genes of the parasite. Detection and identification of Cryptosporidium
      and Blastocystis species and subtypes was carried out by amplification and
      sequencing of a partial fragment of the small-subunit ribosomal RNA gene of both
      protozoan. Analyses of risk factors potentially associated with the transmission
      of these pathogens were also conducted. RESULTS: Prevalences of S. stercoralis,
      G. duodenalis, Cryptosporidium spp., and Blastocystis spp. were estimated at
      21.4% (95% CI: 17.1-25.7%), 37.9% (95% CI: 32.8-43.0%), 2.9% (95% CI: 1.1-4.5%)
      and 25.6% (95% CI: 21.18-30.2%), respectively. Overall, 64.1% (225/351) of the
      children were infected by at least one of the pathogens investigated. Sequence
      analyses of the 28 G. duodenalis isolates that were successfully genotyped
      allowed the identification of sub-assemblages AI (14.3%), AII (14.3%), BIII
      (7.1%) and BIV (25.0%). Discordant typing results AII/AIII and BIII/BIV were
      identified in 7.1% and 14.3% of the isolates, respectively. A total of five
      additional isolates (17.9%) were identified as assemblage B. Three
      Cryptosporidium species including C. hominis (70%), C. parvum (20%) and C. canis
      (10%) were found circulating in the children population under study. A total of
      75 Blastocystis isolates were assigned to the subtypes ST1 (30.7%), ST2 (30.7%),
      ST3 (36.0%), ST5 (1.3%) and ST7 (1.3%), respectively. Children younger than seven
      years of age had significantly higher risk of infections by protozoan
      enteropathogens (PRR: 1.35, P < 0.01), whereas being underweight seemed to have a
      protective effect against these infections (PRR: 0.74, P = 0.005). CONCLUSIONS:
      The burden of disease attributable to human strongyloidiasis, giardiosis,
      cryptosporidiosis and blastocystosis in Angola is considerably higher than
      initially estimated in previous surveys. Surveillance and control of these
      infections should be jointly tackled with formally considered neglected tropical
      diseases in order to maximize effort and available resources. Our data also
      demonstrate the added value of using molecular diagnostic methods in high
      transmission areas.

PMID- 29378627
TI  - Integrated multi-omic analysis of host-microbiota interactions in acute oak
      decline.
AB  - BACKGROUND: Britain's native oak species are currently under threat from acute
      oak decline (AOD), a decline-disease where stem bleeds overlying necrotic lesions
      in the inner bark and larval galleries of the bark-boring beetle, Agrilus
      biguttatus, represent the primary symptoms. It is known that complex interactions
      between the plant host and its microbiome, i.e. the holobiont, significantly
      influence the health status of the plant. In AOD, necrotic lesions are caused by
      a microbiome shift to a pathobiome consisting predominantly of Brenneria
      goodwinii, Gibbsiella quercinecans, Rahnella victoriana and potentially other
      bacteria. However, the specific mechanistic processes of the microbiota causing
      tissue necrosis, and the host response, have not been established and represent a
      barrier to understanding and managing this decline. RESULTS: We profiled the
      metagenome, metatranscriptome and metaproteome of inner bark tissue from AOD
      symptomatic and non-symptomatic trees to characterise microbiota-host
      interactions. Active bacterial virulence factors such as plant cell wall
      degrading enzymes, reactive oxygen species defence and flagella in AOD lesions,
      along with host defence responses including reactive oxygen species, cell wall
      modification and defence regulators were identified. B. goodwinii dominated the
      lesion microbiome, with significant expression of virulence factors such as the
      phytopathogen effector avrE. A smaller proportion of microbiome activity was
      attributed to G. quercinecans and R. victoriana. In addition, we describe for the
      first time the potential role of two previously uncharacterised Gram-positive
      bacteria predicted from metagenomic binning and identified as active in the AOD
      lesion metatranscriptome and metaproteome, implicating them in lesion formation.
      CONCLUSIONS: This multi-omic study provides novel functional insights into
      microbiota-host interactions in AOD, a complex arboreal decline disease where
      polymicrobial-host interactions result in lesion formation on tree stems. We
      present the first descriptions of holobiont function in oak health and disease,
      specifically, the relative lesion activity of B. goodwinii, G. quercinecans,
      Rahnella victoriana and other bacteria. Thus, the research presented here
      provides evidence of some of the mechanisms used by members of the lesion
      microbiome and a template for future multi-omic research into holobiont
      characterisation, plant polymicrobial diseases and pathogen defence in trees.

PMID- 29378628
TI  - Activation of MAP kinases by green leaf volatiles in grasses.
AB  - OBJECTIVE: Previously we have shown that mechanical wounding and volatiles
      released from cut grass, activated a 46 and 44 kDa mitogen-activated protein
      kinase (MAPK) in the model grass species Lolium temulentum (Lt). MAPKs play an
      important role as signal relays that connect incoming stress signals and stress
      responses. Since green leaf volatiles (GLV) are released during wounding, we
      wanted determine if specific compounds contained in the GLV mixture or if GLV
      generated from other plant species could activate these Lt MAPKs. RESULTS: Our
      analysis found that just a 1-min exposure to GLV was enough to activate the Lt 46
      kDa MAPK within 3 min and the 44 kDa MAPK within 15 min. This activation pattern
      showed similar kinetics to those observed after wounding, and the GLV and wound
      activated bands associated with these MAPKs displayed identical migration on
      sodium dodecyl sulfate polyacrylamide gels. Thirteen different commercially
      available plant volatiles (alcohols, aldehydes and ketones) were tested and all
      thirteen volatile compounds were able to activate these same Lt MAPKs.
      Furthermore, GLV derived from three other grass species as well as tomato, a
      dicot, were also shown to activate these MAPKs in Lt.

PMID- 29378629
TI  - An integrative functional genomics framework for effective identification of
      novel regulatory variants in genome-phenome studies.
AB  - BACKGROUND: Genome-phenome studies have identified thousands of variants that are
      statistically associated with disease or traits; however, their functional roles
      are largely unclear. A comprehensive investigation of regulatory mechanisms and
      the gene regulatory networks between phenome-wide association study (PheWAS) and
      genome-wide association study (GWAS) is needed to identify novel regulatory
      variants contributing to risk for human diseases. METHODS: In this study, we
      developed an integrative functional genomics framework that maps 215,107
      significant single nucleotide polymorphism (SNP) traits generated from the PheWAS
      Catalog and 28,870 genome-wide significant SNP traits collected from the GWAS
      Catalog into a global human genome regulatory map via incorporating various
      functional annotation data, including transcription factor (TF)-based motifs,
      promoters, enhancers, and expression quantitative trait loci (eQTLs) generated
      from four major functional genomics databases: FANTOM5, ENCODE, NIH Roadmap, and
      Genotype-Tissue Expression (GTEx). In addition, we performed a tissue-specific
      regulatory circuit analysis through the integration of the identified regulatory
      variants and tissue-specific gene expression profiles in 7051 samples across 32
      tissues from GTEx. RESULTS: We found that the disease-associated loci in both the
      PheWAS and GWAS Catalogs were significantly enriched with functional SNPs. The
      integration of functional annotations significantly improved the power of
      detecting novel associations in PheWAS, through which we found a number of
      functional associations with strong regulatory evidence in the PheWAS Catalog.
      Finally, we constructed tissue-specific regulatory circuits for several complex
      traits: mental diseases, autoimmune diseases, and cancer, via exploring tissue
      specific TF-promoter/enhancer-target gene interaction networks. We uncovered
      several promising tissue-specific regulatory TFs or genes for Alzheimer's disease
      (e.g. ZIC1 and STX1B) and asthma (e.g. CSF3 and IL1RL1). CONCLUSIONS: This study
      offers powerful tools for exploring the functional consequences of variants
      generated from genome-phenome association studies in terms of their mechanisms on
      affecting multiple complex diseases and traits.

PMID- 29378630
TI  - Host genetic variation and its microbiome interactions within the Human
      Microbiome Project.
AB  - BACKGROUND: Despite the increasing recognition that microbial communities within
      the human body are linked to health, we have an incomplete understanding of the
      environmental and molecular interactions that shape the composition of these
      communities. Although host genetic factors play a role in these interactions,
      these factors have remained relatively unexplored given the requirement for large
      population-based cohorts in which both genotyping and microbiome characterization
      have been performed. METHODS: We performed whole-genome sequencing of 298 donors
      from the Human Microbiome Project (HMP) healthy cohort study to accompany
      existing deep characterization of their microbiomes at various body sites. This
      analysis yielded an average sequencing depth of 32x, with which we identified 27
      million (M) single nucleotide variants and 2.3 M insertions-deletions. RESULTS:
      Taxonomic composition and functional potential of the microbiome covaried
      significantly with genetic principal components in the gastrointestinal tract and
      oral communities, but not in the nares or vaginal microbiota. Example
      associations included validation of known associations between FUT2 secretor
      status, as well as a variant conferring hypolactasia near the LCT gene, with
      Bifidobacterium longum abundance in stool. The associations of microbial features
      with both high-level genetic attributes and single variants were specific to
      particular body sites, highlighting the opportunity to find unique genetic
      mechanisms controlling microbiome properties in the microbial communities from
      multiple body sites. CONCLUSIONS: This study adds deep sequencing of host genomes
      to the body-wide microbiome sequences already extant from the HMP healthy cohort,
      creating a unique, versatile, and well-controlled reference for future studies
      seeking to identify host genetic modulators of the microbiome.

PMID- 29378631
TI  - Socio-demographic and sexual practices associated with HIV infection in Kenyan
      injection and non-injection drug users.
AB  - BACKGROUND: Substance use is increasingly becoming prevalent on the African
      continent, fueling the spread of HIV infection. Although socio-demographic
      factors influence substance consumption and risk of HIV infection, the
      association of these factors with HIV infection is poorly understood among
      substance users on the African continent. The objective of the study was to
      assess socio-demographic and sexual practices that are associated with HIV
      infection among injection drug users (IDUs), non-IDUs, and non-drug users (DUs)
      at an urban setting of coastal Kenya. METHODS: A cross-sectional descriptive
      study was conducted among 451 adults comprising HIV-infected and -uninfected IDUs
      (n = 157 and 39); non-IDUs (n = 17 and 48); and non-DUs (n = 55 and 135);
      respectively at coastal, Kenya. Respondent driven sampling, snowball and
      makeshift methods were used to enroll IDUs and non-IDUs. Convenience and
      purposive sampling were used to enroll non-DUs from the hospital's voluntary HIV
      testing unit. Participant assisted questionnaire was used in collecting socio
      demographic data and sexual practices. RESULTS: Binary logistic regression
      analysis indicated that higher likelihood of HIV infection was associated with
      sex for police protection (OR, 9.526; 95% CI, 1.156-78.528; P = 0.036) and
      history of sexually transmitted infection (OR, 5.117; 95% CI, 1.924-13.485; P =
      0.001) in IDUs; divorced, separated or widowed marital status (OR, 6.315; 95% CI,
      1.334-29.898; P = 0.020) in non-IDUs; and unemployment (OR, 2.724; 95% CI, 1.049
      7.070; P = 0.040) in non-drug users. However, never married (single) marital
      status (OR, 0.140; 95% CI, 0.030-0.649; P = 0.012) was associated with lower odds
      for HIV infection in non-drug users. CONCLUSION: Altogether, these results
      suggest that socio-demographic and sexual risk factors for HIV transmission
      differ with drug use status, suggesting targeted preventive measures for drug
      users.

PMID- 29378632
TI  - The effects of a 12-week worksite physical activity intervention on
      anthropometric indices, blood pressure indices, and plasma biomarkers of
      cardiovascular disease risk among university employees.
AB  - BACKGROUND: To determine the effectiveness of a low-cost 12-week worksite
      physical activity intervention targeting a goal of 10,000 steps per day on
      reducing anthropometric indices, blood pressure indices, and plasma biomarkers of
      cardiovascular disease (CVD) risk among the employees of a major university.
      METHODS: Fifty university employees (n = 43 female, n = 7 male; mean age = 48 +/-
      10 years) participated in the 12-week physical activity intervention (60 min, 3
      day/week). Each session included both aerobic (cardiorespiratory endurance) and
      muscle-strengthening (resistance) physical activity using existing university
      facilities and equipment. Anthropometric indices, blood pressure indices, and
      plasma biomarkers of CVD risk assessed included those for obesity (body mass
      index), hypertension (systolic blood pressure, SBP; diastolic blood pressure,
      DBP), dyslipidemia (high-density lipoprotein, HDL; low-density lipoprotein, LDL;
      total serum cholesterol), and prediabetes (impaired fasting glucose, IFG). Steps
      per day were assessed using a wrist-worn activity monitor. Participants were
      given the goal of 10,000 steps per day and categorized as either compliers (>=
      10,000 steps per day on average) or non-compliers (< 10,000 steps per day on
      average) based on their ability to achieve this goal. RESULTS: Overall, 34% of
      participants at baseline were already at an elevated risk of CVD due to age. On
      average, 28% of participants adhered to the goal of 10,000 steps per day. After
      12-weeks, participants in both groups (compliers and non-compliers) had lower BMI
      scores (p < 0.001), lower HDL scores (p < 0.034), and higher IFG scores (p <
      0.001). The non-compliers had a greater reduction of BMI scores than the
      compliers (p = 0.003). Participants at risk for CVD had greater reductions than
      those not at risk for several risk factors, including SBP (p = 0.020), DBP (p =
      0.028), IFG (p = 0.002), LDL (p = 0.006), and total serum cholesterol (p =
      0.009). CONCLUSION: While the physical activity intervention showed mixed results
      overall with both favorable changes in anthropometric indices yet unfavorable
      changes in plasma biomarkers, it was particularly beneficial in regards to both
      blood pressure indices and plasma biomarkers among those already at risk of CVD.
      Trial registration ClinicalTrials.gov NCT03385447; retrospectively registered.

PMID- 29378634
TI  - Evaluating antibody functional activity and strain-specificity of vaccine
      candidates for malaria in pregnancy using in vitro phagocytosis assays.
AB  - BACKGROUND: Malaria in pregnancy is a major cause of poor maternal and infant
      health, and is associated with the sequestration of P. falciparum-infected
      erythrocytes (IE) in the placenta. The leading vaccine candidate for pregnancy
      malaria, VAR2CSA, has been shown to induce antibodies that inhibit IE adhesion to
      the placental receptor chondroitin sulfate A (CSA), potentially preventing
      placental infection. However, the ability of vaccination-induced antibodies to
      promote opsonic phagocytosis is not well defined, but likely to be an important
      component of protective immunity. METHODS: We investigated the use of an opsonic
      phagocytosis assay to evaluate antibodies induced by pregnancy malaria vaccine
      candidate antigens based on VAR2CSA. Opsonic phagocytosis was measured by flow
      cytometry and visualized by electron microscopy. We measured vaccine-induced
      antibody reactivity to placental type IEs from different geographical origins,
      and the functional ability of antibodies raised in immunized rabbits to induce
      phagocytosis by a human monocyte cell line. RESULTS: Immunization-induced
      antibodies showed a mixture of strain-specific and cross-reactive antibody
      recognition of different placental-binding parasite lines. Antibodies generated
      against the DBL5 and DBL3 domains of VAR2CSA effectively promoted the opsonic
      phagocytosis of IEs by human monocytes; however, these functional antibodies were
      largely allele-specific and not cross-reactive. This has significant implications
      for the development of vaccines aiming to achieve a broad coverage against
      diverse parasite strains. Using competition ELISAs, we found that acquired human
      antibodies among pregnant women targeted both cross-reactive and allele-specific
      epitopes, consistent with what we observed with vaccine-induced antibodies.
      CONCLUSIONS: Vaccines based on domains of VAR2CSA induced opsonic phagocytosis of
      IEs in a strain-specific manner. Assays measuring this phagocytic activity have
      the potential to aid the development and evaluation of vaccines against malaria
      in pregnancy.

PMID- 29378635
TI  - Breaking the rules: is it the neurointensivists' turn?

PMID- 29378633
TI  - Commensal microbiota modulate gene expression in the skin.
AB  - BACKGROUND: The skin harbors complex communities of resident microorganisms, yet
      little is known of their physiological roles and the molecular mechanisms that
      mediate cutaneous host-microbe interactions. Here, we profiled skin
      transcriptomes of mice reared in the presence and absence of microbiota to
      elucidate the range of pathways and functions modulated in the skin by the
      microbiota. RESULTS: A total of 2820 genes were differentially regulated in
      response to microbial colonization and were enriched in gene ontology (GO) terms
      related to the host-immune response and epidermal differentiation. Innate immune
      response genes and genes involved in cytokine activity were generally upregulated
      in response to microbiota and included genes encoding toll-like receptors,
      antimicrobial peptides, the complement cascade, and genes involved in IL-1 family
      cytokine signaling and homing of T cells. Our results also reveal a role for the
      microbiota in modulating epidermal differentiation and development, with
      differential expression of genes in the epidermal differentiation complex (EDC).
      Genes with correlated co-expression patterns were enriched in binding sites for
      the transcription factors Klf4, AP-1, and SP-1, all implicated as regulators of
      epidermal differentiation. Finally, we identified transcriptional signatures of
      microbial regulation common to both the skin and the gastrointestinal tract.
      CONCLUSIONS: With this foundational approach, we establish a critical resource
      for understanding the genome-wide implications of microbially mediated gene
      expression in the skin and emphasize prospective ways in which the microbiome
      contributes to skin health and disease.

PMID- 29378637
TI  - Staphylococcal scalded skin syndrome in a 4-year-old child: a case report.
AB  - BACKGROUND: Staphylococcal scalded skin syndrome is an exfoliating skin disease
      which primarily affects children. Differential diagnosis includes toxic epidermal
      necrolysis, staphylococcal scalded skin syndrome, epidermolysis bullosa, and
      Stevens-Johnson syndrome. Staphylococcal scalded skin syndrome primarily affects
      children and can cause serious morbidity. CASE PRESENTATION: In this case report
      we highlight the case of a 4-year-old Caucasian boy. Diagnostic and therapeutic
      challenges are discussed. Differential diagnoses are considered and therapy is
      described and discussed. The latest treatment options are used and described.
      Successful results are achieved in this case due to timely and correct
      management. CONCLUSIONS: Some therapeutic options are widely used without
      thorough research bases. This case report highlights staphylococcal scalded skin
      syndrome and its treatment, and future challenges. Further research is warranted
      and this case report aims to further research in exfoliating skin disorders.

PMID- 29378636
TI  - Traditional uses of medicinal plants used by Indigenous communities for
      veterinary practices at Bajaur Agency, Pakistan.
AB  - BACKGROUND: The pastoral lifestyle of Indigenous communities of Bajaur Agency is
      bringing them close to natural remedies for treating their domestic animals.
      Several studies have been conducted across the globe describing the importance of
      traditional knowledge in veterinary care. Therefore, this study was planned with
      the aim to record knowledge on ethnoveterinary practices from the remote areas
      and share sit with other communities through published literature. METHODS: Data
      was gathered from community members through semi-structured interviews and
      analyzed through informant consensus factor (Fic) to evaluate the consent of
      current ethnoveterinary practices among the local people. RESULTS: In total, 73
      medicinal plants were recorded under the ethnoveterinary practices. Most widely
      used medicinal plants with maximum use reports (URs) were Visnaga daucoides
      Gaertn., Foeniculum vulgare Mill., Solanum virginianum L., Withania somnifera
      (L.) Dunal, Glycyrrhiza glabra L., and Curcuma longa L. New medicinal values were
      found with confidential level of citations for species including Heracleum
      candicans and Glycerhiza glabra. Family Apiaceae was the utmost family with high
      number (7 species) of medicinal plants. Maximum number of medicinal plants (32)
      was used for gastric problems. High Fic was recorded for dermatological (0.97)
      followed by reproductive (0.93) and gastrointestinal disorders (0.92). The main
      route of remedies administration was oral. CONCLUSIONS: Current study revealed
      that the study area has sufficient knowledge on ethnoveterinary medicinal plants.
      This knowledge is in the custody of nomadic grazers, herders, and aged community
      members. Plants with new medicinal uses need to be validated phytochemically and
      pharmacologically for the development of new alternative drugs for veterinary
      purposes.

PMID- 29378638
TI  - Pilot study on an innovative biosensor with a range of medical and surgical
      applications.
AB  - OBJECTIVES: The objective of this article is to briefly outline the utilization
      of biosensors in medicine and surgery and present diagnostic efficacy of thermal
      product (TP) based biosensor. RESULTS: The working principle of biosensor is
      based on measuring TP of a material in contact with the sensor. When an
      electrical square wave pulse of certain amplitude and duration is passed through
      TP based biosensor, the generated heat from its higher resistance will be
      dissipated and recorded by the sensor. As the surrounding material composition
      changes, the dissipated heat split between the sensor substrate and surrounding
      material changes which can be correlated to the change in TP of the material. For
      biological tissues, it is known that the thermal properties of tissues are quite
      different for different layers in the body and hence the heat absorbed will be
      different. The experiments were conducted on biological and non-biological
      tissues. For data acquisition software LabView 2014 (64-bit) was used and
      software used for post-processing was MATLAB R2015a (64-bit). The resulting
      graphs of TP from various materials (oil, water, saline, acetone) and biological
      tissue (porcine belly, porcine thigh layers and porcine abdominal viscera)
      expressed prominent deflections indicating diagnostic efficacy of TP based
      biosensor.

PMID- 29378639
TI  - Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus
      induced acute lung injury in a pig model.
AB  - BACKGROUND: Mesenchymal stem (stromal) cells (MSCs) mediate their
      immunoregulatory and tissue repair functions by secreting paracrine factors,
      including extracellular vesicles (EVs). In several animal models of human
      diseases, MSC-EVs mimic the beneficial effects of MSCs. Influenza viruses cause
      annual outbreaks of acute respiratory illness resulting in significant mortality
      and morbidity. Influenza viruses constantly evolve, thus generating drug
      resistant strains and rendering current vaccines less effective against the newly
      generated strains. Therefore, new therapies that can control virus replication
      and the inflammatory response of the host are needed. The objective of this study
      was to examine if MSC-EV treatment can attenuate influenza virus-induced acute
      lung injury in a preclinical model. METHODS: We isolated EVs from swine bone
      marrow-derived MSCs. Morphology of MSC-EVs was determined by electron microscopy
      and expression of mesenchymal markers was examined by flow cytometry. Next, we
      examined the anti-influenza activity of MSC-EVs in vitro in lung epithelial cells
      and anti-viral and immunomodulatory properties in vivo in a pig model of
      influenza virus. RESULTS: MSC-EVs were isolated from MSC-conditioned medium by
      ultracentrifugation. MSC-EVs were round-shaped and, similarly to MSCs, expressed
      mesenchymal markers and lacked the expression of swine leukocyte antigens I and
      II. Incubation of PKH-26-labeled EVs with lung epithelial cells revealed that MSC
      EVs incorporated into the epithelial cells. Next, we examined the anti-influenza
      and anti-inflammatory properties of MSC-EVs. MSC-EVs inhibited the
      hemagglutination activity of avian, swine, and human influenza viruses at
      concentrations of 1.25-5 MUg/ml. MSC-EVs inhibited influenza virus replication
      and virus-induced apoptosis in lung epithelial cells. The anti-influenza activity
      of MSC-EVs was due to transfer of RNAs from EVs to epithelial cells since pre
      incubation of MSC-EVs with RNase enzyme abrogated the anti-influenza activity of
      MSC-EVs. In a pig model of influenza virus, intratracheal administration of MSC
      EVs 12 h after influenza virus infection significantly reduced virus shedding in
      the nasal swabs, influenza virus replication in the lungs, and virus-induced
      production of proinflammatory cytokines in the lungs of influenza-infected pigs.
      The histopathological findings revealed that MSC-EVs alleviated influenza virus
      induced lung lesions in pigs. CONCLUSIONS: Our data demonstrated in a relevant
      preclinical large animal model of influenza virus that MSC-EVs possessed anti
      influenza and anti-inflammatory properties and that EVs may be used as cell-free
      therapy for influenza in humans.

PMID- 29378640
TI  - Are CONSORT checklists submitted by authors adequately reflecting what
      information is actually reported in published papers?
AB  - BACKGROUND: Compulsory submission of a checklist from the relevant reporting
      guideline is one of the most widespread journal requirements aiming to improve
      completeness of reporting. However, the current suboptimal levels of adherence to
      reporting guidelines observed in the literature may indicate that this journal
      policy is not having a significant effect. FINDINGS: We explored whether authors
      provided the appropriate CONSORT checklist extension for their study and whether
      there were inconsistencies between what authors claimed on the submitted
      checklist and what was actually reported in the published paper. We randomly
      selected 12 randomized trials from three journals that provide the originally
      submitted checklist and analyzed six core CONSORT items. Only one paper used the
      appropriate checklist extension and had no inconsistencies between what was
      claimed in the submitted checklist and what was reported in the published paper.
      CONCLUSION: Journals should take further actions to take full advantage of the
      requirement for the submission of fulfilled CONSORT checklists, thus ensuring
      that these checklists reflect what is reported in the manuscript.

PMID- 29378641
TI  - Intestinal endometriosis combined with colorectal cancer: a case series.
AB  - BACKGROUND: Intestinal endometriosis is a common benign disease among
      menstruating women that affects the intestinal tract. CASE PRESENTATION: This
      case report presents seven Japanese cases of intestinal endometriosis with
      colorectal cancer treated by laparoscopic surgery. Five of the seven cases
      reported here are women presenting with bowel obstruction due to colorectal
      endometriosis with colorectal cancer. It can be confused with serious lesions
      such as advanced colorectal cancer with peritoneal involvement or invasion of
      adjacent organs (T4). CONCLUSIONS: Therefore, we should consider the probability
      that the cause of bowel obstruction is not T4 but intestinal endometriosis. For
      surgical treatment, we recommend laparoscopic surgery for colorectal resection
      because of its benefits of differential diagnosis of T4, preserving fertility,
      and preventing excessive surgical stress. We performed laparoscopic resection in
      seven patients with intestinal endometriosis and colorectal cancer. These cases
      demonstrate the difficulty of establishing a differential diagnosis of intestinal
      endometriosis with colorectal cancer from T4.

PMID- 29378642
TI  - Anti-beta-sheet conformation monoclonal antibody reduces tau and Abeta oligomer
      pathology in an Alzheimer's disease model.
AB  - BACKGROUND: Oligomeric forms of amyloid-beta (Abeta) and tau are increasing being
      recognized as key toxins in the pathogenesis of Alzheimer's disease (AD).
      METHODS: We developed a novel monoclonal antibody (mAb), GW-23B7, that recognizes
      beta-sheet secondary structure on pathological oligomers of neurodegenerative
      diseases. RESULTS: The pentameric immunoglobulin M kappa chain (IgMkappap) we
      developed specifically distinguishes intra- and extracellular pathology in human
      AD brains. Purified GW-23B7 showed a dissociation constant in the nanomolar range
      for oligomeric Abeta and did not bind monomeric Abeta. In enzyme-linked
      immunosorbent assays, it recognized oligomeric forms of both Abeta and
      hyperphosphorylated tau. Aged triple-transgenic AD mice with both Abeta and tau
      pathology infused intraperitoneally for 2 months showed IgMkappap in the soluble
      brain homogenate, peaking at 24 h postinoculation. Treated mice exhibited
      significant cognitive rescue on radial arm maze testing compared with vehicle
      control-infused mice. Immunohistochemically, treatment resulted in a significant
      decrease of extracellular pathology. Biochemically, treatment resulted in
      significant reductions of oligomeric forms of Abeta and tau. CONCLUSIONS: These
      results suggest that GW-23B7, an anti-beta-sheet conformational mAb humanized for
      clinical trials, may be an effective therapeutic agent for human AD.

PMID- 29378643
TI  - A Reproducibility-Based Computational Framework Identifies an Inducible, Enhanced
      Antiviral State in Dendritic Cells from HIV-1 Elite Controllers.
AB  - BACKGROUND: Human immunity relies on the coordinated responses of many cellular
      subsets and functional states. Inter-individual variations in cellular
      composition and communication could thus potentially alter host protection. Here,
      we explore this hypothesis by applying single-cell RNA-sequencing to examine
      viral responses among the dendritic cells (DCs) of three elite controllers (ECs)
      of HIV-1 infection. RESULTS: To overcome the potentially confounding effects of
      donor-to-donor variability, we present a generally applicable computational
      framework for identifying reproducible patterns in gene expression across donors
      who share a unifying classification. Applying it, we discover a highly functional
      antiviral DC state in ECs whose fractional abundance after in vitro exposure to
      HIV-1 correlates with higher CD4+ T cell counts and lower HIV-1 viral loads, and
      that effectively primes polyfunctional T cell responses in vitro. By integrating
      information from existing genomic databases into our reproducibility-based
      analysis, we identify and validate select immunomodulators that increase the
      fractional abundance of this state in primary peripheral blood mononuclear cells
      from healthy individuals in vitro. CONCLUSIONS: Overall, our results demonstrate
      how single-cell approaches can reveal previously unappreciated, yet important,
      immune behaviors and empower rational frameworks for modulating systems-level
      immune responses that may prove therapeutically and prophylactically useful.

PMID- 29378644
TI  - Prevalence of and risk factors for malaria, filariasis, and intestinal parasites
      as single infections or co-infections in different settlements of Gabon, Central
      Africa.
AB  - BACKGROUND: Malaria, filariasis, and intestinal parasitic infections (IPIs) are
      common and frequently overlap in developing countries. The prevalence and
      predictors of these infections were investigated in three different settlements
      (rural, semi-urban, and urban) of Gabon. METHODS: During cross-sectional surveys
      performed from September 2013 to June 2014, 451 individuals were interviewed. In
      addition, blood and stool samples were analysed for the presence of Plasmodium,
      filarial roundworm, intestinal protozoan, and helminth infections. RESULTS:
      Intestinal parasitic infections (61.1%), including intestinal protozoa (56.7%)
      and soil-transmitted helminths (STHs) (22.2%), predominated, whereas Plasmodium
      falciparum (18.8%), Loa loa (4.7%), and Mansonella perstans (1.1%) were less
      prevalent. Filariasis and STHs were mainly found in rural settlements, whereas a
      higher plasmodial infection prevalence rate was observed in the periurban area.
      The most common IPI was blastocystosis (48.6%), followed by ascaridiasis (13.7%),
      trichuriasis (11.8%), amoebiasis (9.3%), giardiasis (4.8%), and strongyloidiasis
      (3.7%). Hookworm was detected in one adult from rural Dienga. Adults had a higher
      prevalence of Blastocystis hominis and STHs, whereas Giardia duodenalis was more
      frequently observed among children aged below 5 years (P < 0.01). The
      polyparasitism rate was 41.5%, with 7.0% Plasmodium-IPIs and 1.8% Plasmodium-STH
      co-infections. The multivariate analysis showed that living in a suburban area,
      belonging to the age group of 5-15 years, having none or a secondary education,
      or having an open body water close to home were significant risk factors for
      malaria (P <= 0.01). For STH infections, identified risk factors were drinking
      untreated water and living in a rural area (P <= 0.04). No significant predictors
      were identified for IPIs and malaria-IPI co-infection. CONCLUSIONS: This study
      reports a high prevalence of IPIs and intestinal protozoa, but a low rate of
      malaria-IPI co-infections in the study sites. Improvements in the living
      conditions of the population such as adequate water supply and proper health
      education and sanitation should be integrated into control strategies for
      malaria, STHs, and IPIs.

PMID- 29378645
TI  - Back-to-back comparison of penKID with NephroCheck(r) to predict acute kidney
      injury at admission in intensive care unit: a brief report.

PMID- 29378646
TI  - Detection and analysis of methicillin-resistant human-adapted sequence type 398
      allows insight into community-associated methicillin-resistant Staphylococcus
      aureus evolution.
AB  - BACKGROUND: Severe infections with highly virulent community-associated
      methicillin-resistant Staphylococcus aureus (CA-MRSA) are a global problem.
      However, the molecular events defining the evolution of CA-MRSA are still poorly
      understood. MRSA of sequence type (ST) 398 is known to frequently infect
      livestock, while ST398 isolates infecting humans are commonly methicillin
      susceptible or represent MRSA originating from livestock-associated (LA)-MRSA.
      METHODS: We used whole genome sequencing of newly detected CA-MRSA ST398
      isolates, in comparison to geographically matched LA-MRSA and methicillin
      sensitive ST398, to determine their evolutionary history. Furthermore, we used
      phenotypic analyses including animal infection models to gain insight into the
      evolution of virulence in these CA-MRSA isolates. Finally, we determined
      methicillin resistance and expression of the methicillin resistance-conferring
      gene mecA and its penicillin-binding protein product, PBP2a, in a large series of
      CA-MRSA strains of divergent STs. RESULTS: We report several cases of severe and
      fatal infections due to ST398 CA-MRSA. The responsible isolates showed the
      typical genetic characteristics reported for human-adapted methicillin-sensitive
      ST398. Whole genome sequencing demonstrated that they evolved from human-adapted,
      methicillin-susceptible clones on several different occasions. Importantly, the
      isolates had not undergone consistent genetic alterations or changes in virulence
      as compared to their methicillin-susceptible predecessors. Finally, we observed
      dramatically and consistently lower methicillin resistance and expression of the
      resistance gene mecA, as compared to hospital-associated MRSA strains, in a
      diverse selection of CA-MRSA strains. CONCLUSIONS: Our study presents evidence
      for the development of highly virulent human-adapted ST398 CA-MRSA isolates from
      methicillin-susceptible predecessors. Notably, our investigation indicates that,
      in contrast to widespread notions, the development of CA-MRSA is not necessarily
      associated with the acquisition of specific virulence genes or other virulence
      increasing changes. Rather, our findings emphasize the importance of the CA-MRSA
      characteristic staphylococcal cassette chromosome mec types, which provide only
      low-level methicillin resistance, for that process. Our findings are of
      particular importance for the diagnosis of CA-MRSA, inasmuch as they indicate
      that the presence of specific virulence genes cannot generally be used for that
      purpose.

PMID- 29378648
TI  - Modulation of mitochondrial activity in HaCaT keratinocytes by the cell
      penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.
AB  - OBJECTIVE: Biologically active cell penetrating peptides (CPPs) are an emerging
      class of therapeutic agent. The wasp venom peptide mastoparan is an established
      CPP that modulates mitochondrial activity and triggers caspase-dependent
      apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP).
      Mitochondrial depolarisation and activation of the caspase cascade also underpins
      the action of dithranol, a topical agent for treatment of psoriasis. The effects
      of a potent mitP analogue on mitochondrial activity were therefore examined to
      assess its potential as a novel approach for targeting mitochondria for the
      treatment of psoriasis. RESULTS: In HaCaT keratinocytes treated with the mitP
      analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial
      activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10
      MUmol L-1, MTT activity was less than 30% that observed in untreated cells.
      Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also
      dissipated the mitochondrial membrane potential, with a threefold increase in
      mitochondrial depolarisation levels. However, caspase activity appeared to be
      reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly
      RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our
      findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity
      but does not appear to evoke apoptosis in HaCaT keratinocytes.

PMID- 29378649
TI  - Correction to: Addressing vulnerability, building resilience: community-based
      adaptation to vector-borne diseases in the context of global change.
AB  - CORRECTION: After publication of this article [1] it came to our attention that
      the name of the author Sadie Ryan was incorrectly shown. Her correct name is
      Sadie J. Ryan.

PMID- 29378647
TI  - Validity of the CR-POSSUM model in surgery for colorectal cancer in Spain (CCR
      CARESS study) and comparison with other models to predict operative mortality.
AB  - BACKGROUND: To validate and recalibrate the CR- POSSUM model and compared its
      discriminatory capacity with other European models such as POSSUM, P-POSSUM, AFC
      or IRCS to predict operative mortality in surgery for colorectal cancer. METHODS:
      Prospective multicenter cohort study from 22 hospitals in Spain. We included
      patients undergoing planned or urgent surgery for primary invasive colorectal
      cancers between June 2010 and December 2012 (N = 2749). Clinical data were
      gathered through medical chart review. We validated and recalibrated the
      predictive models using logistic regression techniques. To calculate the
      discriminatory power of each model, we estimated the areas under the curve - AUC
      (95% CI). We also assessed the calibration of the models by applying the Hosmer
      Lemeshow test. RESULTS: In-hospital mortality was 1.5% and 30-day mortality,
      1.7%. In the validation process, the discriminatory power of the CR-POSSUM for
      predicting in-hospital mortality was 73.6%. However, in the recalibration
      process, the AUCs improved slightly: the CR-POSSUM reached 75.5% (95% CI: 67.3
      83.7). The discriminatory power of the CR-POSSUM for predicting 30-day mortality
      was 74.2% (95% CI: 67.1-81.2) after recalibration; among the other models the
      POSSUM had the greatest discriminatory power, with an AUC of 77.0% (95% CI: 68.9
      85.2). The Hosmer-Lemeshow test showed good fit for all the recalibrated models.
      CONCLUSION: The CR-POSSUM and the other models showed moderate capacity to
      discriminate the risk of operative mortality in our context, where the actual
      operative mortality is low. Nevertheless the IRCS might better predict in
      hospital mortality, with fewer variables, while the CR-POSSUM could be slightly
      better for predicting 30-day mortality. TRAIL REGISTRATION: Registered at:
      ClinicalTrials.gov Identifier: NCT02488161.

PMID- 29378650
TI  - Assessment of kallikrein 6 as a cross-sectional and longitudinal biomarker for
      Alzheimer's disease.
AB  - BACKGROUND: Kallikrein 6 (KLK6) is known to be an age-related protease expressed
      at high levels in the central nervous system. It was previously shown to be
      involved in proteolysis of extracellular proteins implicated in neurodegenerative
      diseases such as Alzheimer's disease (AD), prompting validation of KLK6 as a
      potential biomarker of disease. However, analyses of both plasma and
      cerebrospinal fluid (CSF) levels of KLK6 in patients with AD have been
      inconclusive. We present a detailed analysis of KLK6 in plasma and CSF in two
      separate cohorts in a cross-sectional and a longitudinal clinical setting.
      METHODS: The cross-sectional cohort included control subjects without dementia
      and patients with AD, and the longitudinal cohort included patients with MCI and
      patients with AD followed over a 2-year period. Plasma and CSF levels of KLK6
      were quantified by use of a previously developed and validated enzyme-linked
      immunosorbent assay. Statistical analyses were performed to compare KLK6 levels
      between diagnostic groups and to identify potential associations between KLK6
      level, age, apolipoprotein E (APOE) genotype, total apoE level and the classical
      CSF AD biomarkers. RESULTS: In the cross-sectional setting, KLK6 levels in plasma
      but not in CSF were significantly higher in the AD group than in control
      subjects. CSF but not plasma KLK6 levels were positively correlated with age in
      both the cross-sectional and longitudinal settings. In both cohorts, the CSF KLK6
      levels were significantly and positively correlated with the CSF levels of core
      AD biomarkers. Total plasma and CSF apoE levels were positively associated with
      KLK6 in the cross-sectional study. Finally, during the 2-year monitoring period
      of the longitudinal cohort, CSF KLK6 levels increased with disease progression
      over time in the investigated patient groups. CONCLUSIONS: In two separate
      cohorts we have confirmed the previously reported correlation between age and CSF
      levels of KLK6. Increased plasma KLK6 levels in patients with AD with a more
      advanced disease stage suggest KLK6 as a potential biomarker in patients with AD
      with more severe dementia. Significant correlations between KLK6 levels and core
      CSF AD biomarkers suggest molecular links between KLK6 and AD-related
      pathological processes.

PMID- 29378651
TI  - Safety, tolerability and immunogenicity of an active anti-Abeta40 vaccine
      (ABvac40) in patients with Alzheimer's disease: a randomised, double-blind,
      placebo-controlled, phase I trial.
AB  - BACKGROUND: Immunotherapy targeting the amyloid-beta (Abeta) peptide is a
      promising strategy for the treatment of Alzheimer's disease (AD); however, none
      of the active or passive vaccines tested have been demonstrated to be effective
      to date. We have developed the first active vaccine against the C-terminal end of
      Abeta40, ABvac40, and assessed its safety and tolerability in a phase I clinical
      trial. METHODS: A randomised, double-blind, placebo-controlled, parallel-group,
      phase I study of ABvac40 was conducted with patients aged 50-85 years with mild
      to moderate AD. Participants were entered into three separate groups according to
      time of study entry and were randomly allocated to receive ABvac40 or placebo
      (overall ratio 2:1). The first group received two half-doses of ABvac40 or
      placebo, whereas the second and third groups received two and three full doses,
      respectively. All treatments were administered subcutaneously at 4-week
      intervals. Patients, carers and investigators were blind to treatment allocation
      throughout the study. The primary objective was to assess the safety and
      tolerability of ABvac40 by registering all adverse events (AEs). All patients who
      received at least one dose of treatment were included in the safety analysis. The
      secondary objective was to evaluate the immunogenicity of ABvac40 by titration of
      specific anti-Abeta40 antibodies in plasma. RESULTS: Twenty-four patients were
      randomly allocated: 16 patients to the ABvac40 group and 8 patients to the
      placebo group. All randomised patients completed the study, therefore the
      intention-to-treat and safety populations were identical. Overall, 71 AEs
      affecting 18 patients were recorded: 11 (69%) in the ABvac40 group and 7 (88%) in
      the placebo group (p = 0.6214). Neither incident vasogenic oedema nor sulcal
      effusion (amyloid-related imaging abnormalities corresponding to vasogenic oedema
      and sulcal effusions) nor microhaemorrhages (amyloid-related imaging
      abnormalities corresponding to microhaemorrhages and hemosiderin deposits) were
      detected throughout the study period in the ABvac40-treated patients. Eleven of
      12 (~92%) individuals receiving three injections of ABvac40 developed specific
      anti-Abeta40 antibodies. CONCLUSIONS: ABvac40 showed a favourable safety and
      tolerability profile while eliciting a consistent and specific immune response.
      An ongoing phase II clinical trial is needed to confirm these results and to
      explore the clinical efficacy of ABvac40. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT03113812 . Retrospectively registered on 14 April 2017.

PMID- 29378652
TI  - Fair inclusion of pregnant women in clinical trials: an integrated scientific and
      ethical approach.
AB  - BACKGROUND: Since pregnant women are severely underrepresented in clinical
      research, many take the position that the exclusion of pregnant women from
      research must be justified unless there are compelling "scientific reasons" for
      their exclusion. However, it is questionable whether this approach renders
      research with pregnant women fair. This paper analyzes and evaluates when
      research with pregnant women can be considered as fair and what constitutes
      scientific reasons for exclusion. METHODS: Conceptual ethical and methodological
      analysis and evaluation of fair inclusion. RESULTS: Fair inclusion of pregnant
      women means (1) that pregnant women who are eligible are not excluded solely for
      being pregnant and (2) that the research interests of pregnant women are
      prioritized, meaning that they ought to receive substantially more attention.
      Fairness does not imply that pregnant women should be included in virtually every
      research project, as including only a few pregnant women in a population
      consisting only of women will not help to determine the effectiveness and safety
      of a treatment in pregnant women. Separate trials in pregnant women may be
      preferable once we assume, or know, that effects of interventions in pregnant
      women differ from the effects in other subpopulations, or when we assume, or
      know, that there are no differences. In the latter case, it may be preferable to
      conduct post-marketing studies or establish registries. If there is no conclusive
      evidence indicating either differences or equivalence of effects between pregnant
      and non-pregnant women, yet it seems unlikely that major differences or exact
      equivalence exist, the inclusion of pregnant women should be sufficient.
      Depending on the research question, this boils down to representativeness in
      terms of the proportion of pregnant and non-pregnant women, or to oversampling
      pregnant women. CONCLUSIONS: Fair inclusion of pregnant women in research implies
      that separate trials in pregnant women should be promoted. Inclusion of pregnant
      women has to be realized at the earliest phases of the research process. In
      addition to researchers and research ethics committees, scientific advisory
      councils, funders, drug regulatory agencies, pharmaceutical companies, journal
      editors and others have a joint responsibility to further develop the evidence
      base for drug use in pregnant women.

PMID- 29378653
TI  - Poly herbal formulation with anti-elastase and anti-oxidant properties for skin
      anti-aging.
AB  - BACKGROUND: Skin forms an important part of human innate immune system. Wrinkles,
      thinning and roughening of skin are some of the symptoms that affect the skin as
      it ages. Reactive oxygen species induced oxidative stress plays a major role in
      skin aging by modulating the elastase enzyme level in the skin. Extrinsic factors
      that affect skin aging such as UV radiation can also cause malignant melanoma.
      Here we selected four medicinal plant materials, namely, leaves of Nyctanthes
      arbor-tristis, unripe and ripe Aegle marmelos fruit pulp and the terminal
      meristem of Musa paradisiaca flower and investigated their anti-aging properties
      and cytotoxicity in vitro individually as well as in a poly herbal formulation
      containing the four plant extracts in different ratios. METHODS: The
      phytochemical contents of the plant extracts were investigated for radical
      scavenging activity and total reducing power. Based upon its anti-oxidant
      properties, a poly herbal formulation containing leaves of Nyctanthes arbor
      tristis, unripe and ripe fruit pulp of Aegle marmelos, and the terminal meristem
      of Musa paradisiaca flower in the ratio 6:2:1:1 (Poly Herbal Formulation 1) and
      1:1:1:1 (Poly Herbal Formulation 2), respectively were formulated. RESULT: It has
      been observed that the Poly Herbal Formulation 1 was more potent than Poly Herbal
      Formulation 2 due to better anti-oxidant and anti-elastase activities in NIH3T3
      fibroblast cells. In addition Poly Herbal formulation 1 also had better anti
      cancer activity in human malignant melanoma cells. CONCLUSION: Based on these
      results these beneficial plant extracts were identified for its potential
      application as an anti-aging agent in skin creams as well as an anti
      proliferation compound against cancer cells.

PMID- 29378655
TI  - Elusive implementation: an ethnographic study of intersectoral policymaking for
      health.
AB  - BACKGROUND: For more than 30 years policy action across sectors has been
      celebrated as a necessary and viable way to affect the social factors impacting
      on health. In particular intersectoral action on the social determinants of
      health is considered necessary to address social inequalities in health. However,
      despite growing support for intersectoral policymaking, implementation remains a
      challenge. Critics argue that public health has remained naive about the policy
      process and a better understanding is needed. Based on ethnographic data, this
      paper conducts an in-depth analysis of a local process of intersectoral
      policymaking in order to gain a better understanding of the challenges posed by
      implementation. To help conceptualize the process, we apply the theoretical
      perspective of organizational neo-institutionalism, in particular the concepts of
      rationalized myth and decoupling. METHODS: On the basis of an explorative study
      among ten Danish municipalities, we conducted an ethnographic study of the
      development of a municipal-wide implementation strategy for the intersectoral
      health policy of a medium-sized municipality. The main data sources consist of
      ethnographic field notes from participant observation and interview transcripts.
      RESULTS: By providing detailed contextual description, we show how an apparent
      failure to move from policy to action is played out by the ongoing production of
      abstract rhetoric and vague plans. We find that idealization of universal
      intersectoralism, inconsistent demands, and doubts about economic outcomes
      challenge the notion of implementation as moving from rhetoric to action.
      CONCLUSION: We argue that the 'myth' of intersectoralism may be instrumental in
      avoiding the specification of action to implement the policy, and that the policy
      instead serves as a way to display and support good intentions and hereby
      continue the process. On this basis we expand the discussion on implementation
      challenges regarding intersectoral policymaking for health.

PMID- 29378654
TI  - Exceptional in vivo catabolism of neurodegeneration-related aggregates.
AB  - Neurodegenerative diseases are linked to a systemic enzyme resistance of toxic
      aggregated molecules and their pathological consequences. This paper presents a
      unique phenomenon that Philodina acuticornis, a bdelloid rotifer, is able to
      catabolize different types of neurotoxic peptide and protein aggregates (such as
      beta-amyloids /Abeta/, alpha-synuclein, and prion) without suffering any damage.
      P. acuticornis is capable of using these aggregates as an exclusive energy source
      (i.e., as 'food', identified in the digestive system and body) in a hermetically
      isolated microdrop environment, increasing their survival. As regards Abeta1-42,
      five other bdelloid rotifer species were also found to be able to perform this
      phenomenon. Based on our experiments, the Abeta1-42-treated bdelloid rotifers
      demonstrate significantly increased survival (e.g. mean lifespan = 51 +/- 2.71
      days) compared to their untreated controls (e.g. mean lifespan = 14 +/- 2.29
      days), with similar improvements in a variety of phenotypic characteristics. To
      our knowledge, no other animal species have so far been reported to have a
      similar capability. For all other microscopic species tested, including
      monogonant rotifers and non-rotifers, the treatment with Abeta1-42 aggregates
      proved to be either toxic or simply ineffective. This paper describes and proves
      the existence of an unprecedented in vivo catabolic capability of neurotoxic
      aggregates by bdelloid rotifers, with special focus on P. acuticornis. Our
      results may provide the basis for a new preclinical perspective on therapeutic
      research in human neurodegenerative diseases.

PMID- 29378656
TI  - Navigation problems of ICSI or naive blastocyst can be solved with artificial
      blastocyst.
AB  - Embryos have evolved a remarkable capacity to find implantation site. The
      impressive navigation ability of natural blastocysts may rely on highly sensitive
      signals arising from embryos and specialized signal processing strategies in the
      endometrium. Navigation capabilities may be compromised in ICSI embryos because
      of altered biochemical signaling. The design and delivery of artificial
      blastocyst (AB) carrying strong chemical signals may allow ICSI embryos to more
      easily locate to and be retained in the implantation zone. ICSI embryos will
      attach easily to the implantation zone after it is found by the AB. Co-transfer
      of the AB together with the ICSI embryo may overcome potential difficulties in
      implantation due to impaired embryo-maternal communication in cases with
      implantation failure.

PMID- 29378658
TI  - Who benefits from increased service utilisation? Examining the distributional
      effects of payment for performance in Tanzania.
AB  - BACKGROUND: Payment for performance (P4P) strategies, which provide financial
      incentives to health workers and/or facilities for reaching pre-defined
      performance targets, can improve healthcare utilisation and quality. P4P may also
      reduce inequalities in healthcare use and access by enhancing universal access to
      care, for example, through reducing the financial barriers to accessing care.
      However, P4P may also enhance inequalities in healthcare if providers cherry-pick
      the easier-to-reach patients to meet their performance targets. In this study, we
      examine the heterogeneity of P4P effects on service utilisation across population
      subgroups and its implications for inequalities in Tanzania. METHODS: We used
      household data from an evaluation of a P4P programme in Tanzania. We surveyed
      about 3000 households with women who delivered in the last 12 months prior to the
      interview from seven intervention and four comparison districts in January 2012
      and a similar number of households in 13 months later. The household data were
      used to generate the population subgroups and to measure the incentivised service
      utilisation outcomes. We focused on two outcomes that improved significantly
      under the P4P, i.e. institutional delivery rate and the uptake of antimalarials
      for pregnant women. We used a difference-in-differences linear regression model
      to estimate the effect of P4P on utilisation outcomes across the different
      population subgroups. RESULTS: P4P led to a significant increase in the rate of
      institutional deliveries among women in poorest and in middle wealth status
      households, but not among women in least poor households. However, the
      differential effect was marginally greater among women in the middle wealth
      households compared to women in the least poor households (p = 0.094). The effect
      of P4P on institutional deliveries was also significantly higher among women in
      rural districts compared to women in urban districts (p = 0.028 for differential
      effect), and among uninsured women than insured women (p = 0.001 for differential
      effect). The effect of P4P on the uptake of antimalarials was equally distributed
      across population subgroups. CONCLUSION: P4P can enhance equitable healthcare
      access and use especially when the demand-side barriers to access care such as
      user fees associated with drug purchase due to stock-outs have been reduced.

PMID- 29378659
TI  - Diagnostic performance of 18F-FDG PET/CT using point spread function
      reconstruction on initial staging of rectal cancer: a comparison study with
      conventional PET/CT and pelvic MRI.
AB  - BACKGROUND: Accurate staging is crucial for treatment selection and prognosis
      prediction in patients with rectal cancer. Point spread function (PSF)
      reconstruction can improve spatial resolution and signal-to-noise ratio of PET
      imaging. The aim of this study was to evaluate the effectiveness of 18F-FDG
      PET/CT with PSF reconstruction for initial staging in rectal cancer compared with
      conventional PET/CT and pelvic MRI. METHODS: A total of 59 patients with rectal
      cancer underwent preoperative 18F-FDG PET/CT and pelvic MRI. The maximum
      standardized uptake value (SUVmax) and lesion to background (L/B) ratio of
      possible metastatic lymph nodes, and metabolic tumor volumes (MTVs) of primary
      tumors were calculated. For N and T (T1-2 vs T3-4) staging, sensitivities,
      specificities, positive predictive values, negative predictive values, and
      accuracies were compared between conventional PET/CT [reconstructed with ordered
      subset expectation maximization (OSEM)], PSF-PET/CT (reconstructed with
      OSEM+PSF), and pelvic MRI. Histopathologic analysis was the reference standard.
      RESULTS: For N staging, PSF-PET/CT provided higher sensitivity (78.6%) than
      conventional PET/CT (64.3%), and pelvic MRI (57.1%), and all techniques showed
      high specificity (PSF-PET: 95.4%, conventional PET: 96.7%, pelvic MRI: 93.5%).
      SUVmax and L/B ratio were significantly higher in PSF-PET/CT than conventional
      PET/CT (p < 0.001). The accuracy for T staging in PSF-PET/CT (69.4%) was not
      significantly different to conventional PET/CT (73.5%) and pelvic MRI (73.5%).
      MTVs of PSF and conventional PET showed a significant difference among T stages
      (p < 0.001), with higher values in advanced stages. In M staging, both PSF and
      conventional PET/CT diagnosed all distant metastases correctly. CONCLUSIONS: PSF
      PET/CT produced images with higher lesion-to-background contrast than
      conventional PET/CT, which allowed improved detection of lymph node metastasis
      without compromising specificity, and showed comparable diagnostic value to MRI
      in local staging. PSF-PET/CT is likely to have a great value for initial staging
      in rectal cancer.

PMID- 29378657
TI  - What do we measure when we measure cell-associated HIV RNA.
AB  - Cell-associated (CA) HIV RNA has received much attention in recent years as a
      surrogate measure of the efficiency of HIV latency reversion and because it may
      provide an estimate of the viral reservoir size. This review provides an update
      on some recent insights in the biology and clinical utility of this biomarker. We
      discuss a number of important considerations to be taken into account when
      interpreting CA HIV RNA measurements, as well as different methods to measure
      this biomarker.

PMID- 29378660
TI  - Clinical activity of nivolumab in patients with non-clear cell renal cell
      carcinoma.
AB  - BACKGROUND: Nivolumab is approved for patients with metastatic renal cell
      carcinoma (mRCC) refractory to prior antiangiogenic therapy. The clinical
      activity of nivolumab in patients with non-clear cell RCC subtypes remains
      unknown as these patients were excluded from the original nivolumab trials.
      METHODS: Patients from 6 centers in the United States who received at least one
      dose of nivolumab for non-clear cell mRCC between 12/2015 and 06/2017 were
      identified. A retrospective analysis including patient characteristics, objective
      response rate according to RECIST v1.1 and treatment-related adverse events
      (TRAEs) was undertaken. RESULTS: Forty-one patients were identified. Median age
      was 58 years (33-82), 71% were male, and majority had ECOG PS 0 (40%) or 1 (47%).
      Histology included 16 papillary, 14 unclassified, 5 chromophobe, 4 collecting
      duct, 1 Xp11 translocation and 1 MTSCC (mucinous tubular and spindle cell
      carcinoma). Among 35 patients who were evaluable for best response, 7 (20%) had
      PR and 10 (29%) had SD. Responses were observed in unclassified, papillary and
      collecting duct subtypes. In the entire cohort, median follow-up was 8.5 months
      and median treatment duration was 3.0 months. Median PFS was 3.5 months and
      median OS was not reached. Among responders, median time to best response was 5.1
      months, and median duration of response was not reached as only 2 out of 7
      responders had disease progression during follow-up. TRAEs of any grade were
      noted in 37% and most commonly included fatigue (12%), fever (10%) and rash
      (10%). Nivolumab treatments were postponed in 34% and discontinued in 15% of
      patients due to intolerance. No treatment-related deaths were observed.
      CONCLUSIONS: Nivolumab monotherapy demonstrated objective responses and was well
      tolerated in a heterogeneous population of patients with non-clear cell mRCC. In
      the absence of other data in this treatment setting, this study lends support to
      the use of nivolumab for patients with metastatic non-clear cell renal cell
      carcinoma.

PMID- 29378661
TI  - Doctor-your septic patients have scurvy!

PMID- 29378662
TI  - The effectiveness and cost-effectiveness of 3- vs. 6-monthly dispensing of
      antiretroviral treatment (ART) for stable HIV patients in community ART-refill
      groups in Zimbabwe: study protocol for a pragmatic, cluster-randomized trial.
AB  - BACKGROUND: Sub-Saharan Africa is the world region with the greatest number of
      people eligible to receive antiretroviral treatment (ART). Less frequent
      dispensing of ART and community-based ART-delivery models are potential
      strategies to reduce the load on overburdened healthcare facilities and reduce
      the barriers for patients to access treatment. However, no large-scale trials
      have been conducted investigating patient outcomes or evaluating the cost
      effectiveness of extended ART-dispensing intervals within community ART-delivery
      models. This trial will assess the clinical effectiveness, cost-effectiveness and
      acceptability of providing ART refills on a 3 vs. a 6-monthly basis within
      community ART-refill groups (CARGs) for stable patients in Zimbabwe. METHODS: In
      this pragmatic, three-arm, parallel, unblinded, cluster-randomized non
      inferiority trial, 30 clusters (healthcare facilities and associated CARGs) are
      allocated using stratified randomization in a 1:1:1 ratio to either (1) ART
      refills supplied 3-monthly from the health facility (control arm), (2) ART
      refills supplied 3-monthly within CARGs, or (3) ART refills supplied 6-monthly
      within CARGs. A CARG consists of 6-12 stable patients who meet in the community
      to receive ART refills and who provide support to one another. Stable adult ART
      patients with a baseline viral load < 1000 copies/ml will be invited to
      participate (1920 participants per arm). The primary outcome is the proportion of
      participants alive and retained in care 12 months after enrollment. Secondary
      outcomes (measured at 12 and 24 months) are the proportions achieving virological
      suppression, average provider cost per participant, provider cost per participant
      retained, cost per participant retained with virological suppression, and average
      patient-level costs to access treatment. Qualitative research will assess the
      acceptability of extended ART-dispensing intervals within CARGs to both providers
      and patients, and indicators of potential facility-level decongestion due to the
      interventions will be assessed. DISCUSSION: Cost-effective health system models
      that sustain high levels of patient retention are urgently needed to accommodate
      the large numbers of stable ART patients in sub-Saharan Africa. This will be the
      first trial to evaluate extended ART-dispensing intervals within a community
      based ART distribution model, and results are intended to inform national and
      regional policy regarding their potential benefits to both the healthcare system
      and patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03238846 .
      Registered on 27 July 2017.

PMID- 29378663
TI  - Early diagnosis of tuberous sclerosis complex: a race against time. How to make
      the diagnosis before seizures?
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder with an
      incidence of 1:6000 live births and associated with the development of benign
      tumors in several organs. It is also characterized by high rates of neurological
      and neuropsychiatric abnormalities, including epilepsy affecting 70-90% of
      patients and being one of the major risk factors of intellectual disability. The
      first seizures in TSC patients appear usually between the 4th and the 6th months
      of life. Recent studies have shown the beneficial role of preventative
      antiepileptic treatment in TSC patients, with the possibility for improvement of
      cognitive outcome. Moreover, European recommendations suggest early introduction
      of Vigabatrin if ictal discharges occur on EEG recordings, with or without
      clinical manifestation. The aim of this study was to define the most useful
      approach to make the diagnosis of TSC before seizure onset (before age 4th
      months), in order to start early EEG monitoring with possible preventative
      treatment intervention. METHODS: We performed a retrospective review of children
      who were suspected of having TSC due to single or multiple cardiac tumors as the
      first sign of the disease. We analyzed the medical records in terms of conducted
      clinical tests and TSC signs, which were observed until the end of the 4th month
      of age. Subsequently, we described the different clinical scenarios and
      recommendations for early diagnosis. RESULTS: 82/100 children were diagnosed with
      TSC within the first 4 months of life. Apart from cardiac tumors, the most
      frequently observed early TSC signs were subependymal nodules (71/100, 71%),
      cortical dysplasia (66/100, 66%), and hypomelanotic macules (35/100, 35%). The
      most useful clinical studies for early TSC diagnosis were brain magnetic
      resonance imaging (MRI), skin examination and echocardiography. Genetic testing
      was performed in 49/100 of the patients, but the results were obtained within the
      first 4 months of life in only 3 children. CONCLUSIONS: Early diagnosis of TSC,
      before seizure onset, is feasible and it is becoming pivotal for epilepsy
      management and improvement of cognitive outcome. Early TSC diagnosis is mostly
      based on clinical signs. Brain MRI, echocardiography, skin examination and
      genetic testing should be performed early in every patient suspected of having
      TSC.

PMID- 29378664
TI  - The prevalence of human papillomavirus in pediatric tonsils: a systematic review
      of the literature.
AB  - BACKGROUND: HPV-related head and neck cancer rates have been increasing in recent
      years, with the tonsils being the most commonly affected site. However, the
      current rate of HPV infection in the pediatric population remains poorly defined.
      The objective of this study was to systematically review and evaluate the
      prevalence and distribution of HPV in the tonsils of pediatric patients
      undergoing routine tonsillectomy. METHODS AND RESULTS: The literature was
      searched using PubMed, EMBASE, Scopus, CINAHL, Cochrane Library, and ProQuest
      Dissertations & Theses Global databases (inception to December 2017) by two
      independent review authors. Inclusion criteria included articles which evaluated
      the prevalence of HPV in a pediatric cohort without known warts or recurrent
      respiratory papillomatosis, those which used tonsil biopsy specimens for
      analysis, and those with six or more subjects and clear outcomes reported. Eleven
      studies met the inclusion criteria. Using the Oxford Clinical Evidence-based
      Medicine (OCEBM) guidelines, two reviewers appraised the level of evidence of
      each study, extracted data, and resolved discrepancies by consensus. The
      systematic review identified 11 articles (n = 2520). Seven studies detected HPV
      in the subject population, with prevalence values ranging from 0 to 21%. The
      level of evidence for all included studies was OCEBM Level 3. CONCLUSIONS: HPV
      may be present in pediatric tonsillectomy specimens; however, the largest
      included study demonstrated a prevalence of 0%. Future testing should be
      performed using methods with high sensitivities and specificities, such as
      reverse transcript real-time PCR or digital droplet PCR.

PMID- 29378665
TI  - Identification of novel candidate genes for 46,XY disorders of sex development
      (DSD) using a C57BL/6J-Y POS mouse model.
AB  - BACKGROUND: Disorders of sex development (DSD) have an estimated frequency of
      0.5% of live births encompassing a variety of urogenital anomalies ranging from
      mild hypospadias to a discrepancy between sex chromosomes and external genitalia.
      In order to identify the underlying genetic etiology, we had performed exome
      sequencing in a subset of DSD cases with 46,XY karyotype and were able to
      identify the causative genetic variant in 35% of cases. While the genetic
      etiology was not ascertained in more than half of the cases, a large number of
      variants of unknown clinical significance (VUS) were identified in those exomes.
      METHODS: To investigate the relevance of these VUS in regards to the patient's
      phenotype, we utilized a mouse model in which the presence of a Y chromosome from
      the poschiavinus strain (Y POS ) on a C57BL/6J (B6) background results in XY
      undervirilization and sex reversal, a phenotype characteristic to a large subset
      of human 46,XY DSD cases. We assessed gene expression differences between B6-Y B6
      and undervirilized B6-Y POS gonads at E11.5 and identified 515 differentially
      expressed genes (308 underexpressed and 207 overexpressed in B6-Y POS males).
      RESULTS: We identified 15 novel candidate genes potentially involved in 46,XY DSD
      pathogenesis by filtering the list of human VUS-carrying genes provided by exome
      sequencing with the list of differentially expressed genes from B6-Y POS mouse
      model. Additionally, we identified that 7 of the 15 candidate genes were
      significantly underexpressed in the XY gonads of mice with suppressed Sox9
      expression in Sertoli cells suggesting that some of the candidate genes may be
      downstream of a well-known sex determining gene, Sox9. CONCLUSION: The use of a
      DSD-specific animal model improves variant interpretation by correlating human
      sequence variants with transcriptome variation.

PMID- 29378666
TI  - Supply factors as determinants of treatment costs: clinicians' assessments of a
      given set of referrals to community mental health centers in Norway.
AB  - BACKGROUND: Previous works that uses patterns of prior spending to predict future
      mental health care expenses (utilization models) are mainly concerned with demand
      (need) variables. In this paper, we introduce supply variables, both individual
      rater variables and center variables. The aim is to assess these variables'
      explanatory power, and to investigate whether not accounting for such variables
      could create biased estimates for the effects of need variables. METHODS: We
      employed an observational study design where the same set of referrals was
      assessed by a sample of clinicians, thus creating data with a panel structure
      being particularly relevant for analyzing supply factors. The referrals were
      obtained from Norwegian Community Mental Health Centers (outpatient services),
      and the clinicians assessed the referrals with respect to recommended treatment
      costs and health status. RESULTS: Supply variables accounted for more than 10% of
      the total variation and about one third of the explained variation. Two groups of
      supply variables, individual rater variables and center variables (institutions)
      were equally important. CONCLUSIONS: Our results confirm that supply factors are
      important but ignoring such variables, when analyzing demand variables, do not
      generally seem to produce biased (confounded) coefficients.

PMID- 29378667
TI  - Saving Lives at Birth; development of a retrospective theory of change, impact
      framework and prioritised metrics.
AB  - BACKGROUND: Grand Challenges for international health and development initiatives
      have received substantial funding to tackle unsolved problems; however, evidence
      of their effectiveness in achieving change is lacking. A theory of change may
      provide a useful tool to track progress towards desired outcomes. The Saving
      Lives at Birth partnership aims to address inequities in maternal-newborn
      survival through the provision of strategic investments for the development,
      testing and transition-to-scale of ground-breaking prevention and treatment
      approaches with the potential to leapfrog conventional healthcare approaches in
      low resource settings. We aimed to develop a theory of change and impact
      framework with prioritised metrics to map the initiative's contribution towards
      overall goals, and to measure progress towards improved outcomes around the time
      of birth. METHODS: A theory of change and impact framework was developed
      retrospectively, drawing on expertise across the partnership and stakeholders.
      This included a document and literature review, and wide consultation, with
      feedback from stakeholders at all stages. Possible indicators were reviewed from
      global maternal-newborn health-related partner initiatives, priority indicator
      lists, and project indicators from current innovators. These indicators were
      scored across five domains to prioritise those most relevant and feasible for
      Saving Lives at Birth. These results informed the identification of the
      prioritised metrics for the initiative. RESULTS: The pathway to scale through
      Saving Lives at Birth is articulated through a theory of change and impact
      framework, which also highlight the roles of different actors involved in the
      programme. A prioritised metrics toolkit, including ten core impact indicators
      and five additional process indicators, complement the theory of change. The
      retrospective nature of this development enabled structured reflection of the
      program mechanics, allowing for inclusion of learning from the first four rounds
      of the program to inform implementation of subsequent rounds. CONCLUSIONS: While
      theories of change are more traditionally developed before program
      implementation, retrospective development can still be a useful exercise for
      multi-round programs like Saving Lives at Birth, where outputs from the
      development can be used to strengthen subsequent rounds. However, identifying a
      uniform set of prioritised metrics for use across the portfolio proved more
      challenging. Lessons learnt from this exercise will be relevant to the
      development of pathways to change across other Grand Challenges and global health
      platforms.

PMID- 29378670
TI  - Engaging emergency clinicians in emergency department clinical research.
AB  - OBJECTIVE: The objective of this panel was to generate recommendations to promote
      the engagement of front-line emergency department (ED) clinicians in clinical and
      implementation research. METHODS: Panel members conducted semi-structured
      interviews with 37 Canadian adult and pediatric emergency medicine researchers to
      elicit barriers and facilitators to clinician engagement in research activities,
      and to glean strategies for promoting clinician engagement. RESULTS: Responses
      were organized by themes, and, based on these responses, recommendations were
      developed and refined in an iterative fashion by panel members. CONCLUSIONS: We
      offer eight recommendations to promote front-line clinician engagement in
      clinical research activities. Recommendations to promote clinician engagement
      specifically address the creation of a research-friendly culture in the ED,
      minimizing the burden of data collection on clinical staff through the careful
      design of data collection tools and the use of research staff, and communication
      between researchers and clinical staff to promote adherence to study protocols.

PMID- 29378669
TI  - Canadian Pediatric Antimicrobial Stewardship Programs: Current Resources and
      Implementation Characteristics.
AB  - Antimicrobial stewardship programs (ASPs) became an accreditation requirement for
      Canadian hospitals in 2013. Pediatric programs are in various stages of program
      development and implementation, with 93% of surveyed Canadian academic pediatric
      hospitals having established ASPs. The programs varied in their team composition,
      implementation of stewardship strategies, and measured metrics. Infect Control
      Hosp Epidemiol 2018;39:350-354.

PMID- 29378668
TI  - Genome-wide analysis reveals a role for TDG in estrogen receptor-mediated
      enhancer RNA transcription and 3-dimensional reorganization.
AB  - BACKGROUND: The estrogen receptor (ER) is a ligand-dependant transcription factor
      expressed in many breast cancers and is the target of many endocrine-based cancer
      therapies. Genome-wide studies have shown that the ER binds to gene-specific
      enhancer regions in response to beta-estradiol (E2) which undergo transcription
      producing noncoding enhancer RNA (eRNA). While eRNAs are important for
      transcriptional activation of neighboring genes, the mechanism remains poorly
      understood. RESULTS: Using ChIP-Seq we generate a global profile of thymine DNA
      glycosylase (TDG), an ER coactivator that plays an essential role in DNA
      demethylation, in response to E2 in the MCF7 breast cancer cell line. Remarkably,
      we found that in response to E2 TDG localized to enhancers which also recruit
      ERalpha, RNA Pol II and other coregulators and which are marked by histone
      modifications indicative of active enhancers. Importantly, depletion of TDG
      inhibits E2-mediated transcription of eRNAs and transcription of ER-target genes.
      Functionally, we find that TDG both sensitizes MCF7 cells to tamoxifen-mediated
      cytostasis and increases migration and invasion of MCF7 cells. CONCLUSIONS: Taken
      together we find that TDG plays a central role in mediating transcription at a
      subset of enhancers and governs how MCF7 cells respond to both estrogenic and
      anti-estrogenic compounds and may be an effective therapeutic target.

PMID- 29378671
TI  - How to conduct implementation trials and multicentre studies in the emergency
      department.
AB  - OBJECTIVE: The objective of Panel 2b was to present an overview of and
      recommendations for the conduct of implementation trials and multicentre studies
      in emergency medicine. METHODS: Panel members engaged methodologists to discuss
      the design and conduct of implementation and multicentre studies. We also
      conducted semi-structured interviews with 37 Canadian adult and pediatric
      emergency medicine researchers to elicit barriers and facilitators to conducting
      these kinds of studies. RESULTS: Responses were organized by themes, and, based
      on these responses, recommendations were developed and refined in an iterative
      fashion by panel members. CONCLUSIONS: We offer eight recommendations to
      facilitate multicentre clinical and implementation studies, along with guidance
      for conducting implementation research in the emergency department.
      Recommendations for multicentre studies reflect the importance of local study
      investigators and champions, requirements for research infrastructure and
      staffing, and the cooperation and communication between the coordinating centre
      and participating sites.

PMID- 29378672
TI  - Patient, Provider, and Practice Characteristics Associated with Inappropriate
      Antimicrobial Prescribing in Ambulatory Practices.
AB  - OBJECTIVE To reduce inappropriate antimicrobial prescribing across ambulatory
      care, understanding the patient-, provider-, and practice-level characteristics
      associated with antibiotic prescribing is essential. In this study, we aimed to
      elucidate factors associated with inappropriate antimicrobial prescribing across
      urgent care, family medicine, and pediatric and internal medicine ambulatory
      practices. DESIGN, SETTING, AND PARTICIPANTS Data for this retrospective cohort
      study were collected from outpatient visits for common upper respiratory
      conditions that should not require antibiotics. The cohort included 448,990
      visits between January 2014 and May 2016. Carolinas HealthCare System urgent
      care, family medicine, internal medicine and pediatric practices were included
      across 898 providers and 246 practices. METHODS Prescribing rates were reported
      per 1,000 visits. Indications were defined using the International Classification
      of Disease, Ninth and Tenth Revisions, Clinical Modification (ICD-9/10-CM)
      criteria. In multivariable models, the risk of receiving an antibiotic
      prescription was reported with adjustment for practice, provider, and patient
      characteristics. RESULTS The overall prescribing rate in the study cohort was 407
      per 1,000 visits (95% confidence interval [CI], 405-408). After adjustment, adult
      patients seen by an advanced practice practitioner were 15% more likely to
      receive an antimicrobial than those seen by a physician provider (incident risk
      ratio [IRR], 1.15; 95% CI, 1.03-1.29). In the pediatric sample, older providers
      were 4 times more likely to prescribe an antimicrobial than providers aged <=30
      years (IRR, 4.21; 95% CI, 2.96-5.97). CONCLUSIONS Our results suggest that
      patient, practice, and provider characteristics are associated with inappropriate
      antimicrobial prescribing. Future research should target antibiotic stewardship
      programs to specific patient and provider populations to reduce inappropriate
      prescribing compared to a "one size fits all" approach. Infect Control Hosp
      Epidemiol 2018;39:307-315.

PMID- 29378673
TI  - Guidance on Frequency and Location of Environmental Sampling for Acinetobacter
      baumannii.
AB  - We assessed various locations and frequency of environmental sampling to maximize
      information and maintain efficiency when sampling for Acinetobacter baumannii.
      Although sampling sites in closer proximity to the patient were more likely
      positive, to fully capture environmental contamination, we found value in
      sampling all sites and across multiple days. Infect Control Hosp Epidemiol
      2018;39:339-342.

PMID- 29378674
TI  - Wiping Is Inferior to Rubbing: A Note of Caution for Hand Hygiene With Alcohol
      Based Solutions.
AB  - We evaluated whether hand wiping is noninferior to hand rubbing in reducing the
      bacterial concentration on hands. In 20 healthy volunteers, hand wiping with or
      without an alcohol-based solution was inferior to hand rubbing with an alcohol
      based solution. This finding warrants a note of caution for the application of
      wipes in health care. Infect Control Hosp Epidemiol 2018;39:332-335.

PMID- 29378676
TI  - A case of bullous pemphigoid with IgG antibodies against LAD-1, but not BP180
      NC16a domain or BP230.

PMID- 29378675
TI  - Therapeutic effects of telomerase in mice with pulmonary fibrosis induced by
      damage to the lungs and short telomeres.
AB  - Pulmonary fibrosis is a fatal lung disease characterized by fibrotic foci and
      inflammatory infiltrates. Short telomeres can impair tissue regeneration and are
      found both in hereditary and sporadic cases. We show here that telomerase
      expression using AAV9 vectors shows therapeutic effects in a mouse model of
      pulmonary fibrosis owing to a low-dose bleomycin insult and short telomeres. AAV9
      preferentially targets regenerative alveolar type II cells (ATII). AAV9-Tert
      treated mice show improved lung function and lower inflammation and fibrosis at 1
      3 weeks after viral treatment, and improvement or disappearance of the fibrosis
      at 8 weeks after treatment. AAV9-Tert treatment leads to longer telomeres and
      increased proliferation of ATII cells, as well as lower DNA damage, apoptosis,
      and senescence. Transcriptome analysis of ATII cells confirms downregulation of
      fibrosis and inflammation pathways. We provide a proof-of-principle that
      telomerase activation may represent an effective treatment for pulmonary fibrosis
      provoked or associated with short telomeres.

PMID- 29378677
TI  - Pyoderma gangrenosum in the genital area: successful treatment using adalimumab.

PMID- 29378678
TI  - Type D (CD8+) lymphomatoid papulosis in a patient with classic (CD4+) mycosis
      fungoides.

PMID- 29378679
TI  - Itraconazole: an incidental clearance of recalcitrant warts?

PMID- 29378681
TI  - Improving access to eating disorder services.

PMID- 29378680
TI  - Continuous glucose monitoring to evaluate glycaemic abnormalities in cystic
      fibrosis.
AB  - OBJECTIVE: This study aimed to determine the glycaemic profile of patients with
      cystic fibrosis using a continuous glucose monitoring system (CGMS), and to
      evaluate the associations of glycaemic abnormalities with sex, age, pubertal
      stage, CFTR gene mutations, nutritional status, lung function, oral glucose
      tolerance test, glycated haemoglobin concentrations, fasting insulin
      concentrations, C peptide concentrations and exocrine pancreatic function. STUDY
      DESIGN: This observational study evaluated CGMS data from 39 patients with cystic
      fibrosis who were treated at a referral centre. The patients were 10-19.9 years
      old, and were categorised according to whether they had normal results (27
      patients) or glucose intolerance (12 patients) during the oral glucose tolerance
      test. RESULTS: The maximum interstitial glucose concentration among individuals
      with normal oral glucose tolerance test results was 174.9+/-65.1 mg/dL (9.7-3.61
      mmol/L), compared with 170.4+/-40.9 mg/dL (9.46-2.27 mmol/L) among individuals
      with glucose intolerance. The CGMS revealed that 18 of the 27 patients with
      normal oral glucose tolerance test results had peak interstitial glucose
      concentrations of >140 mg/dL (7.8 mmol/L), and that 4 of these individuals had
      peak levels of >200 mg/dL (11.1 mmol/L). None of the analysed clinical or
      laboratory characteristics predicted the occurrence of hyperglycaemic peaks on
      CGMS. CONCLUSIONS: The present study revealed that CGMS could detect
      hyperglycaemia among patients with cystic fibrosis and 'normal' oral glucose
      tolerance test results, and that their clinical and laboratory characteristics
      were not useful in discerning between patients who did and did not exhibit these
      excursions.

PMID- 29378682
TI  - New cancer drugs fund keeps within L340m a year budget.

PMID- 29378683
TI  - Response to: 'Association between bisphosphonate use and risk of undergoing knee
      replacement in osteoarthritis patients' by Chen et al.

PMID- 29378684
TI  - End non-essential use of antimicrobials in livestock.

PMID- 29378685
TI  - Assessment and management of oesophago-gastric cancer: summary of NICE guidance.

PMID- 29378686
TI  - Homelessness and public health.

PMID- 29378687
TI  - Health experts urge UK and EU to "put patients first" in Brexit talks.

PMID- 29378688
TI  - From DESI to the MasSpec Pen: Ambient Ionization Mass Spectrometry for Tissue
      Analysis and Intrasurgical Cancer Diagnosis.

PMID- 29378689
TI  - Robust and Accurate 2-Year Performance of a Quantitative Mass Spectrometry-Based
      Apolipoprotein Test in a Clinical Chemistry Laboratory.

PMID- 29378690
TI  - Celgene Targets Blood Cancers with Major Buys.
AB  - Celgene acquired Juno Therapeutics for $9 billion and is spending up to $7
      billion on Impact Biomedicines in an effort to diversify its hematology portfolio
      with chimeric antigen receptor T-cell therapies and a JAK2 inhibitor before its
      best seller, lenalidomide, faces competition from generics.

PMID- 29378691
TI  - Former USA Gymnastics team doctor sentenced for abusing hundreds of girl
      athletes.

PMID- 29378692
TI  - Association Between Hospital Volume, Processes of Care, and Outcomes in Patients
      Admitted With Heart Failure: Insights From Get With The Guidelines-Heart Failure.
AB  - BACKGROUND: Hospital volume is frequently used as a structural metric for
      assessing quality of care, but its utility in patients admitted with acute heart
      failure (HF) is not well characterized. Accordingly, we sought to determine the
      relationship between admission volume, process-of-care metrics, and short- and
      long-term outcomes in patients admitted with acute HF. METHODS: Patients enrolled
      in the Get With The Guidelines-HF registry with linked Medicare inpatient data at
      342 hospitals were assessed. Volume was assessed both as a continuous variable,
      and quartiles based on the admitting hospital annual HF case volume, as well: 5
      to 38 (quartile 1), 39 to 77 (quartile 2), 78 to 122 (quartile 3), 123 to 457
      (quartile 4). The main outcome measures were (1) process measures at discharge
      (achievement of HF achievement, quality, reporting, and composite metrics); (2)
      30-day mortality and hospital readmission; and (3) 6-month mortality and hospital
      readmission. Adjusted logistic and Cox proportional hazards models were used to
      study these associations with hospital volume. RESULTS: A total of 125 595
      patients with HF were included. Patients admitted to high-volume hospitals had a
      higher burden of comorbidities. On multivariable modeling, lower-volume hospitals
      were significantly less likely to be adherent to HF process measures than higher
      volume hospitals. Higher hospital volume was not associated with a difference in
      in-hospital (odds ratio, 0.99; 95% confidence interval [CI], 0.94-1.05; P=0.78)
      or 30-day mortality (hazard ratio, 0.99; 95% CI, 0.97-1.01; P=0.26), or 30-day
      readmissions (hazard ratio, 0.99; 95% CI, 0.97-1.00; P=0.10). There was a weak
      association of higher volumes with lower 6-month mortality (hazard ratio, 0.98;
      95% CI, 0.97-0.99; P=0.001) and lower 6-month all-cause readmissions (hazard
      ratio, 0.98; 95%, CI 0.97-1.00; P=0.025). CONCLUSIONS: Our analysis of a large
      contemporary prospective national quality improvement registry of older patients
      with HF indicates that hospital volume as a structural metric correlates with
      process measures, but not with 30-day outcomes, and only marginally with outcomes
      up to 6 months of follow-up. Hospital profiling should focus on participation in
      systems of care, adherence to process metrics, and risk-standardized outcomes
      rather than on hospital volume itself.

PMID- 29378693
TI  - Friends and family test should no longer be mandatory.

PMID- 29378694
TI  - Prognostic Significance of PD-L1+ and CD8+ Immune Cells in HPV+ Oropharyngeal
      Squamous Cell Carcinoma.
AB  - Human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC)
      represents a distinct subgroup of head and neck cancers associated with clinical
      outcomes that are not accurately categorized by existing tumor-node-metastasis
      based staging methods. Given the significant impact of immune parameters, such as
      tumor-infiltrating lymphocytes (TIL) in many cancers, we sought to determine if
      immunophenotyping tumors can improve categorization of HPV+ OPSCCs for prognostic
      purposes. In a cohort of 190 patients with HPV+ OPSCC, we quantified and
      determined the localization of CD8+ TILs, as well as PD-L1-expressing tumor cells
      (TC) and immune cells (IC). The prognostic significance of these parameters on
      overall survival (OS) was evaluated, and their contribution to existing
      prognostic models was determined. High CD8+ TIL abundance (>=30% on stromal or
      intratumoral ICs) was seen in 61.3% patients and was associated with improved OS
      [HR, 0.4; 95% confidence interval (CI), 0.2-0.9; P = 0.017]. Although the
      expression of PD-L1 on TC was not prognostic, high expression of PD-L1 on >=5% of
      intratumoral ICs was found in 38.5% patients and was significantly associated
      with improved OS (HR, 0.37; 95% CI, 0.15-0.93; P = 0. 023). Both high
      intratumoral IC PD-L1 expression and abundant CD8+ TILs in HPV+ OPSCCs identify
      subgroups of patients with excellent outcomes and provide additional prognostic
      information beyond existing staging systems. Cancer Immunol Res; 6(3); 1-10.
      (c)2018 AACR.

PMID- 29378695
TI  - How I treat type 2B von Willebrand disease.
AB  - Type 2B von Willebrand disease (VWD) is an inherited bleeding disorder caused by
      changes in von Willebrand factor (VWF) that enhance binding of VWF to GPIb on
      platelets. Although this disorder is seemingly well defined because of this
      single molecular defect, in reality type 2B VWD is a clinically heterogeneous
      disorder that can be difficult to identify and manage. Diagnostic criteria
      include a history of mucocutaneous bleeding, laboratory studies showing enhanced
      VWF binding of platelets and/or a 2B VWD genetic variant, and a family history
      consistent with autosomal dominant inheritance. Thrombocytopenia, although not
      always present, is common and can be exacerbated by physiologic stressors such as
      pregnancy. The mainstay of therapy for type 2B VWD is VWF replacement therapy.
      Adjunct therapies useful in other types of VWD, such as antifibrinolytics, are
      also used in type 2B VWD. 1-Desamino-8-d-arginine vasopressin (DDAVP) is
      controversial because of exacerbation of thrombocytopenia, but is, in practice,
      sometimes used for minor bleeding. Here we review the available evidence and
      provide 3 clinical cases to illustrate the intricacies of diagnosing type 2B VWD
      to describe the response to DDAVP and to review complexities and management
      during pregnancy.

PMID- 29378696
TI  - BAFF and CD4+ T cells are major survival factors for long-lived splenic plasma
      cells in a B-cell-depletion context.
AB  - Previous data have suggested that B-cell-depletion therapy may induce the
      settlement of autoreactive long-lived plasma cells (LLPCs) in the spleen of
      patients with autoimmune cytopenia. To investigate this process, we used the AID
      CreERT2-EYFP mouse model to follow plasma cells (PCs) engaged in an immune
      response. Multiplex polymerase chain reaction at the single-cell level revealed
      that only a small fraction of splenic PCs had a long-lived signature, whereas PCs
      present after anti-CD20 antibody treatment appeared more mature, similar to bone
      marrow PCs. This observation suggested that, in addition to a process of
      selection, a maturation induced on B-cell depletion drove PCs toward a long-lived
      program. We showed that B-cell activating factor (BAFF) and CD4+ T cells play a
      major role in the PC survival niche, because combining anti-CD20 with anti-BAFF
      or anti-CD4 antibody greatly reduce the number of splenic PCs. Similar results
      were obtained in the lupus-prone NZB/W model. These different contributions of
      soluble and cellular components of the PC niche in the spleen demonstrate that
      the LLPC expression profile is not cell intrinsic but largely depends on signals
      provided by the splenic microenvironment, implying that interfering with these
      components at the time of B-cell depletion might improve the response rate in
      autoimmune cytopenia.

PMID- 29378697
TI  - Alternatives to the face-to-face consultation in general practice: focused
      ethnographic case study.
AB  - BACKGROUND: NHS policy encourages general practices to introduce alternatives to
      the face-to-face consultation, such as telephone, email, e-consultation systems,
      or internet video. Most have been slow to adopt these, citing concerns about
      workload. This project builds on previous research by focusing on the experiences
      of patients and practitioners who have used one or more of these alternatives.
      AIM: To understand how, under what conditions, for which patients, and in what
      ways, alternatives to face-to-face consultations present benefits and challenges
      to patients and practitioners in general practice. DESIGN AND SETTING: Focused
      ethnographic case studies took place in eight UK general practices between June
      2015 and March 2016. METHOD: Non-participant observation, informal conversations
      with staff, and semi-structured interviews with staff and patients were
      conducted. Practice documents and protocols were reviewed. Data were analysed
      through charting and the 'one sheet of paper' mind-map method to identify the
      line of argument in each thematic report. RESULTS: Case study practices had
      different rationales for offering alternatives to the face-to-face consultation.
      Beliefs varied about which patients and health issues were suitable. Co-workers
      were often unaware of each other's practice; for example, practice policies for
      use of e-consultations systems with patients were not known about or followed.
      Patients reported benefits including convenience and access. Staff and some
      patients regarded the face-to-face consultation as the ideal. CONCLUSION:
      Experience of implementing alternatives to the face-to-face consultation suggests
      that changes in patient access and staff workload may be both modest and gradual.
      Practices planning to implement them should consider carefully their reasons for
      doing so and involve the whole practice team.

PMID- 29378698
TI  - Sexual orientation disclosure in health care: a systematic review.
AB  - BACKGROUND: Significant health disparities between sexual minority individuals
      (that is, lesbian, gay, bisexual, or transgender [LGBT]) and heterosexual
      individuals have been demonstrated. AIM: To understand the barriers and
      facilitators to sexual orientation (SO) disclosure experienced by LGBT adults in
      healthcare settings. DESIGN AND SETTING: Mixed methods systematic review,
      including qualitative, quantitative, and mixed methods papers following PRISMA
      guidelines. METHOD: Study quality was assessed using the Mixed Methods Appraisal
      Tool (MMAT) and a qualitative synthesis was performed. Studies were included if
      their participants were aged >=18 years who either identified as LGBT, had a same
      sex sexual relationship, or were attracted to a member of the same sex. RESULTS:
      The review included 31 studies representing 2442 participants. Four overarching
      themes were identified as barriers or facilitators to SO disclosure: the moment
      of disclosure, the expected outcome of disclosure, the healthcare professional,
      and the environment or setting of disclosure. The most prominent themes were the
      perceived relevance of SO to care, the communication skills and language used by
      healthcare professionals, and the fear of poor treatment or reaction to
      disclosure. CONCLUSION: The facilitators and barriers to SO disclosure by LGBT
      individuals are widespread but most were modifiable and could therefore be
      targeted to improve healthcare professionals' awareness of their patients' SO.
      Healthcare professionals should be aware of the broad range of factors that
      influence SO disclosure and the potential disadvantageous effects of non
      disclosure on care. The environment in which patients are seen should be
      welcoming of different SOs as well as ensuring that healthcare professionals'
      communication skills, both verbal and non-verbal, are accepting and inclusive.

PMID- 29378699
TI  - Use of primary care data to predict those most vulnerable to cold weather: a case
      crossover analysis.
AB  - BACKGROUND: The National Institute for Health and Care Excellence (NICE)
      recommends that GPs use routinely available data to identify patients most at
      risk of death and ill health from living in cold homes. AIM: To investigate
      whether sociodemographic characteristics, clinical factors, and house energy
      efficiency characteristics could predict cold-related mortality. DESIGN AND
      SETTING: A case-crossover analysis was conducted on 34 777 patients aged >=65
      years from the Clinical Practice Research Datalink who died between April 2012
      and March 2014. The average temperature of date of death and 3 days previously
      were calculated from Met Office data. The average 3-day temperature for the 28th
      day before/after date of death were calculated, and comparisons were made between
      these temperatures and those experienced around the date of death. METHOD:
      Conditional logistic regression was applied to estimate the odds ratio (OR) of
      death associated with temperature and interactions between temperature and
      sociodemographic characteristics, clinical factors, and house energy efficiency
      characteristics, expressed as relative odds ratios (RORs). RESULTS: Lower 3-day
      temperature was associated with higher risk of death (OR 1.011 per 1 degrees C
      fall; 95% CI = 1.007 to 1.015; P<0.001). No modifying effects were observed for
      sociodemographic characteristics, clinical factors, and house energy efficiency
      characteristics. Analysis of winter deaths for causes typically associated with
      excess winter mortality (N = 7710) showed some evidence of a weaker effect of
      lower 3-day temperature for females (ROR 0.980 per 1 degrees C, 95% CI = 0.959 to
      1.002, P = 0.082), and a stronger effect for patients living in northern England
      (ROR 1.040 per 1 degrees C, 95% CI = 1.013 to 1.066, P = 0.002). CONCLUSION: It
      is unlikely that GPs can identify older patients at highest risk of cold-related
      death using routinely available data, and NICE may need to refine its guidance.

PMID- 29378700
TI  - Bawa-Garba case has left profession shaken and stirred.

PMID- 29378701
TI  - Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection
      using human induced neural stem cells.
AB  - Zika virus (ZIKV) is a mosquito-transmitted flavivirus with a causative link to
      microcephaly, a condition resulting in reduced cranial size and brain
      abnormalities. Despite recent progress, there is a current lack of in vivo models
      that permit the study of systemic virus on human neurons in a developing organism
      that replicates the pathophysiology of human disease. Furthermore, no treatment
      to date has been reported to reduce ZIKV-induced microcephaly. We tested the
      effects of ZIKV on human induced neural stem cells (hiNSCs) in vitro and found
      that infected hiNSCs secrete inflammatory cytokines, display altered
      differentiation, and become apoptotic. We also utilized this in vitro system to
      assess the therapeutic effects of niclosamide, an FDA-approved anthelminthic, and
      found that it decreases ZIKV production, partially restores differentiation, and
      prevents apoptosis in hiNSCs. We intracranially injected hiNSCs into developing
      chicks, subjected them to systemic ZIKV infection via the chorioallantoic
      membrane (CAM), a tissue similar in structure and function to the mammalian
      placenta, and found that humanized ZIKV-infected embryos developed severe
      microcephaly including smaller crania, decreased forebrain volume and enlarged
      ventricles. Lastly, we utilized this humanized model to show that CAM-delivery of
      niclosamide can partially rescue ZIKV-induced microcephaly and attenuate
      infection of hiNSCs in vivoThis article has an associated First Person interview
      with the first author of the paper.

PMID- 29378702
TI  - Dnd1-mediated epigenetic control of teratoma formation in mouse.
AB  - Spontaneous testicular teratoma develops from primordial germ cells (PGCs) in
      embryos; however, the molecular mechanisms underlying teratoma formation are not
      fully understood. Mutation of the dead-end 1 (Dnd1) gene, which encodes an RNA
      binding protein, drastically enhances teratoma formation in the 129/Sv mouse
      strain. To elucidate the mechanism of Dnd1 mutation-induced teratoma formation,
      we focused on histone H3 lysine 27 (H3K27) trimethylation (me3), and found that
      the levels of H3K27me3 and its responsible methyltransferase, enhancer of zeste
      homolog 2 (Ezh2), were decreased in the teratoma-forming cells of Dnd1 mutant
      embryos. We also showed that Dnd1 suppressed miR-26a-mediated inhibition of Ezh2
      expression, and that Dnd1 deficiency resulted in decreased H3K27me3 of a cell
      cycle regulator gene, Ccnd1 In addition, Ezh2 expression or Ccnd1 deficiency
      repressed the reprogramming of PGCs into pluripotent stem cells, which mimicked
      the conversion of embryonic germ cells into teratoma-forming cells. These results
      revealed an epigenetic molecular linkage between Dnd1 and the suppression of
      testicular teratoma formation.

PMID- 29378703
TI  - Population Pharmacokinetics and Dosing Optimization of Ceftazidime in Infants.
AB  - Ceftazidime, a third-generation cephalosporin, can be used for the treatment of
      adults and children with infections due to susceptible bacteria. To date, the
      pediatric pharmacokinetic data are limited in infants, and therefore we aimed to
      evaluate the population pharmacokinetics of ceftazidime in infants and to define
      the appropriate dose to optimize ceftazidime treatment. Blood samples were
      collected from children treated with ceftazidime, and concentrations of the drug
      were quantified by high-performance liquid chromatography with UV detection (HPLC
      UV). A population pharmacokinetic analysis was performed using NONMEM software
      (version 7.2.0). Fifty-one infants (age range, 0.1 to 2.0 years) were included.
      Sparse pharmacokinetic samples (n = 90) were available for analysis. A one
      compartment model with first-order elimination showed the best fit with the data.
      A covariate analysis identified that body weight and creatinine clearance (CLCR)
      were significant covariates influencing ceftazidime clearance. Monte Carlo
      simulation demonstrated that the currently used dosing regimen of 50 mg/kg twice
      daily was associated with a high risk of underdosing in infants. In order to
      reach the target of 70% of the time that the free antimicrobial drug
      concentration exceeds the MIC (fT>MIC), 25 mg/kg every 8 h (q8h) and 50 mg/kg q8h
      were required for MICs of 4 and 8 mg/liter, respectively. The population
      pharmacokinetic characteristics of ceftazidime were evaluated in infants. An
      evidence-based dosing regimen was established based on simulation.

PMID- 29378704
TI  - Impact of Vancomycin MIC on Clinical Outcomes of Patients with Methicillin
      Resistant Staphylococcus aureus Bacteremia Treated with Vancomycin at an
      Institution with Suppressed MIC Reporting.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of
      bacteremia and is associated with significant morbidity and mortality. Prior
      studies evaluating the association of vancomycin MICs with clinical outcomes in
      patients with MRSA bacteremia have been inconsistent. This study evaluated the
      association between vancomycin MICs and 30-day in-hospital mortality rates for
      patients with MRSA bacteremia. This was a retrospective cohort study of patients
      with MRSA bacteremia treated with vancomycin for >=72 h from January 2013 to
      August 2016. Vancomycin MICs were determined by broth microdilution via automated
      susceptibility testing methods. Study groups consisted of patients with MRSA
      isolates that had vancomycin MICs of <2 MUg/ml and those with vancomycin MICs of
      2 MUg/ml. Covariates included demographics, severity of illness, comorbidities,
      intensive-care unit (ICU) admission, infectious disease consultation, infectious
      sources, and hospital onset of bacteremia. The primary outcome was 30-day in
      hospital mortality. Secondary outcomes included the duration of bacteremia,
      persistent bacteremia for >=7 days, recurrence within 30 days, change to
      alternative antibiotic therapy, and length of hospital stay. Multivariate
      logistic regression models were analyzed to control for potential confounding
      variables. A total of 166 patients were included for analysis: 91 patients with
      vancomycin MICs of <2 MUg/ml and 75 patients with vancomycin MICs of 2 MUg/ml. In
      the multivariate logistic regression model, a vancomycin MIC of 2 MUg/ml,
      compared to a MIC of <2 MUg/ml, was not significantly associated with 30-day in
      hospital mortality after adjustment for confounders. Additionally, all secondary
      outcomes were not statistically significantly different between study groups. In
      patients with MRSA bacteremia treated with vancomycin, the vancomycin MIC was not
      associated with differences in clinical outcomes.

PMID- 29378705
TI  - Roles of Three Cryptococcus neoformans and Cryptococcus gattii Efflux Pump-Coding
      Genes in Response to Drug Treatment.
AB  - Cryptococcus neoformans and Cryptococcus gattii species complexes are the
      etiologic agents of cryptococcosis. We have deciphered the roles of three ABC
      transporters, Afr1, Afr2, and Mdr1, in the representative strains of the two
      species, C. neoformans H99 and C. gattii R265. Deletion of AFR1 in H99 and R265
      drastically reduced the levels of resistance to three xenobiotics and three
      triazoles, suggesting that Afr1 is the major drug efflux pump in both strains.
      Fluconazole susceptibility was not affected when AFR2 or MDR1 was deleted in both
      strains. However, when these genes were deleted in combination with AFR1, a minor
      additive effect in susceptibility toward several drugs was observed. Deletion of
      all three genes in both strains caused further increases in susceptibility toward
      fluconazole and itraconazole, suggesting that Afr2 and Mdr1 augment Afr1 function
      in pumping these triazoles. Intracellular accumulation of Nile Red significantly
      increased in afr1Delta mutants of both strains, but rhodamine 6G accumulation
      increased only in the mdr1Delta mutant of H99. Thus, the three efflux pumps play
      different roles in the two strains when exposed to different azoles and
      xenobiotics. AFR1 and AFR2 expression was upregulated in H99 and R265 when
      treated with fluconazole. However, MDR1 expression was upregulated only in R265
      under the same conditions. We screened a library of transcription factor mutants
      and identified several mutants that manifested either altered fluconazole
      sensitivity or an increase in the frequency of fluconazole heteroresistance. Gene
      expression analysis suggests that the three efflux pumps are regulated
      independently by different transcription factors in response to fluconazole
      exposure.

PMID- 29378706
TI  - In Vivo Pharmacokinetics and Pharmacodynamics of APX001 against Candida spp. in a
      Neutropenic Disseminated Candidiasis Mouse Model.
AB  - APX001 is the prodrug of APX001A, which is a first-in-class small molecule with a
      unique mechanism of action that inhibits the fungal enzyme Gwt1 in the
      glycosylphosphatidylinositol (GPI) biosynthesis pathway. The goal of the present
      study was to determine which pharmacokinetic/pharmacodynamic (PK/PD) index and
      magnitude best correlated with efficacy in the murine disseminated candidiasis
      model for Candida albicans (n = 5), C. glabrata (n = 5), and C. auris (n = 4).
      MIC values ranged from 0.002 to 0.03 mg/liter for C. albicans, from 0.008 to 0.06
      mg/liter for C. glabrata, and from 0.004 to 0.03 mg/liter for C. auris Plasma
      APX001A pharmacokinetic measurements were performed in mice after oral
      administration of 4, 16, 64, and 256 mg/kg of body weight APX001. Single-dose
      pharmacokinetic studies exhibited maximum plasma concentration (Cmax) values of
      0.46 to 15.6 mg/liter, area under the concentration-time curve (AUC) from time
      zero to infinity (AUC0-inf) values of 0.87 to 70.0 mg . h/liter, and half-lives
      of 1.40 to 2.75 h. A neutropenic murine disseminated candidiasis model was
      utilized for all treatment studies, and drug dosing was by the oral route. Dose
      fractionation was performed against C. albicans K1, with total doses ranging from
      4 to 1,024 mg/kg/day of APX001 fractionated into regimens of dosing every 3, 6,
      8, and 12 h for a 24-h treatment duration. Nonlinear regression analysis was used
      to determine which PK/PD index best correlated with efficacy on the basis of the
      reduction in the number of CFU/kidney at 24 h. The 24-h free-drug AUC/MIC ratio
      (fAUC0-24/MIC) was the PK/PD index that best correlated with efficacy
      (coefficient of determination [R2] = 0.88). Treatment studies with the remaining
      strains utilized regimens of 1 to 256 mg/kg of APX001 administered every 6 h for
      a 24-h duration with C. albicans and a 96-h study duration with C. glabrata and
      C. auris The dose required to achieve 50% of the maximum effect (ED50) and stasis
      fAUC/MIC targets were as follows: for C. albicans, 3.67 +/- 3.19 and 20.60 +/-
      6.50, respectively; for C. glabrata, 0.38 +/- 0.21 and 1.31 +/- 0.27,
      respectively; and for C. auris, 7.14 +/- 4.54 and 14.67 +/- 8.30, respectively.
      The present studies demonstrated in vitro and in vivo APX001A and APX001 potency,
      respectively, against C. albicans, C. glabrata, and C. auris. These results have
      potential relevance for clinical dose selection and evaluation of susceptibility
      breakpoints. The identification of a lower AUC/MIC ratio target for C. glabrata
      suggests that species-specific susceptibility breakpoints should be explored.

PMID- 29378707
TI  - Azithromycin Resistance in Shigella spp. in Southeast Asia.
AB  - Infection by Shigella spp. is a common cause of dysentery in Southeast Asia.
      Antimicrobials are thought to be beneficial for treatment; however, antimicrobial
      resistance in Shigella spp. is becoming widespread. We aimed to assess the
      frequency and mechanisms associated with decreased susceptibility to azithromycin
      in Southeast Asian Shigella isolates and use these data to assess appropriate
      susceptibility breakpoints. Shigella isolates recovered in Vietnam and Laos were
      screened for susceptibility to azithromycin (15 MUg) by disc diffusion and MIC.
      Phenotypic resistance was confirmed by PCR amplification of macrolide resistance
      loci. We compared the genetic relationships and plasmid contents of azithromycin
      resistant Shigella sonnei isolates using whole-genome sequences. From 475
      available Shigella spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181
      S. flexneri isolates (3.3%, MIC >= 16 g/liter) and 16/294 S. sonnei isolates
      (5.4%, MIC >= 32 g/liter) were phenotypically resistant to azithromycin. PCR
      amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (mphA in
      19 isolates and ermB in 3 isolates). The susceptibility data demonstrated the
      acceptability of the S. flexneri (MIC >= 16 g/liter, zone diameter <= 15 mm) and
      S. sonnei (MIC >= 32 g/liter, zone diameter <= 11 mm) breakpoints with a <3%
      discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has
      arisen sporadically in Vietnamese S. sonnei isolates on at least seven occasions
      between 2000 and 2009 but failed to become established. While the proposed
      susceptibility breakpoints may allow better recognition of resistant isolates,
      additional studies are required to assess the impact on the clinical outcome. The
      potential emergence of azithromycin resistance highlights the need for
      alternative options for management of Shigella infections in countries where
      Shigella is endemic.

PMID- 29378708
TI  - A Multicenter, Randomized, Double-Blind, Phase 2 Study of the Efficacy and Safety
      of Plazomicin Compared with Levofloxacin in the Treatment of Complicated Urinary
      Tract Infection and Acute Pyelonephritis.
AB  - Increasing antimicrobial resistance among uropathogens limits treatment options
      for patients with complicated urinary tract infection (cUTI). Plazomicin, a new
      aminoglycoside, has in vitro activity against multidrug-resistant
      Enterobacteriaceae, including isolates resistant to currently available
      aminoglycosides, as well as extended-spectrum beta-lactamase-producing and
      carbapenem-resistant Enterobacteriaceae We evaluated the efficacy and safety of
      plazomicin in a double-blind, comparator-controlled, phase 2 study in adults with
      cUTI or acute pyelonephritis. Patients were randomized 1:1:1 to receive
      intravenous plazomicin (10 or 15 mg/kg of body weight) or intravenous
      levofloxacin (750 mg) once daily for 5 days. Coprimary efficacy endpoints were
      microbiological eradication at the test of cure (TOC; 5 to 12 days after the last
      dose) in the modified intent-to-treat (MITT) and microbiologically evaluable (ME)
      populations. Overall, 145 patients were randomized to treatment. In the groups
      receiving plazomicin at 10 mg/kg, plazomicin at 15 mg/kg, and levofloxacin,
      microbiological eradication rates were, respectively, 50.0% (6 patients with
      microbiological eradication at TOC/12 patients treated [95% confidence interval
      {CI}, 21.1 to 78.9%]), 60.8% (31/51 [95% CI, 46.1 to 74.2%]), and 58.6% (17/29
      [95% CI, 38.9 to 76.5%]) in the MITT population and 85.7% (6/7 [95% CI, 42.1 to
      99.6%]), 88.6% (31/35 [95% CI, 73.3 to 96.8%]), and 81.0% (17/21 [95% CI, 58.1 to
      94.6%]) in the ME population. In the MITT population, 66.7% (95% CI, 34.9 to
      90.1%), 70.6% (95% CI, 56.2 to 82.5%), and 65.5% (95% CI, 45.7 to 82.1%) of the
      patients in the three groups, respectively, were assessed by the investigator to
      be clinically cured at TOC. Adverse events were reported in 31.8%, 35.1%, and
      47.7% of the patients in the three groups, respectively. Serum creatinine values
      were generally stable over the course of the study. No plazomicin-treated
      patients with evaluable audiometry data had postbaseline sensorineural,
      conductive, or mixed hearing loss. In summary, plazomicin demonstrated
      microbiological and clinical success and an overall safety profile supportive of
      further clinical development. (This study has been registered at
      ClinicalTrials.gov under identifier NCT01096849.).

PMID- 29378709
TI  - Antibiotic Susceptibility and Genotyping of Mycobacterium avium Strains That
      Cause Pulmonary and Disseminated Infection.
AB  - Mycobacterium avium subsp. hominissuis mainly causes disseminated infection in
      immunocompromised hosts, such as individuals with human immunodeficiency virus
      (HIV) infection, and pulmonary infection in immunocompetent hosts. However, many
      aspects of the different types of M. avium subsp. hominissuis infection remain
      unclear. We examined the antibiotic susceptibilities and genotypes of M. avium
      subsp. hominissuis isolates from different hosts by performing drug
      susceptibility testing using eight antibiotics (clarithromycin, rifampin,
      ethambutol, streptomycin, kanamycin, amikacin, ethionamide, and levofloxacin) and
      variable-number tandem-repeat (VNTR) typing analysis for 46 isolates from the
      sputa of HIV-negative patients with pulmonary M. avium subsp. hominissuis disease
      without previous antibiotic treatment and 30 isolates from the blood of HIV
      positive patients with disseminated M. avium subsp. hominissuis disease.
      Interestingly, isolates from pulmonary M. avium subsp. hominissuis disease
      patients were more resistant to seven of the eight drugs, with the exception
      being rifampin, than isolates from HIV-positive patients. Moreover, VNTR typing
      analysis showed that the strains examined in this study were roughly classified
      into three clusters, and the genetic distance from reference strain 104 for
      isolates from pulmonary M. avium subsp. hominissuis disease patients was
      statistically significantly different from that for isolates from HIV-positive
      patients (P = 0.0018), suggesting that M. avium subsp. hominissuis strains that
      cause pulmonary and disseminated disease have genetically distinct features.
      Significant differences in susceptibility to seven of the eight drugs, with the
      exception being ethambutol, were noted among the three clusters. Collectively,
      these results suggest that an association between the type of M. avium subsp.
      hominissuis infection, drug susceptibility, and the VNTR genotype and the
      properties of M. avium subsp. hominissuis strains associated with the development
      of pulmonary disease are involved in higher levels of antibiotic resistance.

PMID- 29378710
TI  - Evaluation of a System-Specific Function To Describe the Pharmacokinetics of
      Benzylpenicillin in Term Neonates Undergoing Moderate Hypothermia.
AB  - The pharmacokinetic (PK) properties of intravenous (i.v.) benzylpenicillin in
      term neonates undergoing moderate hypothermia after perinatal asphyxia were
      evaluated, as they have been unknown until now. A system-specific modeling
      approach was applied, in which our recently developed covariate model describing
      developmental and temperature-induced changes in amoxicillin clearance (CL) in
      the same patient study population was incorporated into a population PK model of
      benzylpenicillin with a priori birthweight (BW)-based allometric scaling.
      Pediatric population covariate models describing the developmental changes in
      drug elimination may constitute system-specific information and may therefore be
      incorporated into PK models of drugs cleared through the same pathway. The
      performance of this system-specific model was compared to that of a reference
      model. Furthermore, Monte-Carlo simulations were performed to evaluate the
      optimal dose. The system-specific model performed as well as the reference model.
      Significant correlations were found between CL and postnatal age (PNA),
      gestational age (GA), body temperature (TEMP), urine output (UO; system-specific
      model), and multiorgan failure (reference model). For a typical patient with a GA
      of 40 weeks, BW of 3,000 g, PNA of 2 days (TEMP, 33.5 degrees C), and normal UO
      (2 ml/kg/h), benzylpenicillin CL was 0.48 liter/h (interindividual variability
      [IIV] of 49%) and the volume of distribution of the central compartment was 0.62
      liter/kg (IIV of 53%) in the system-specific model. Based on simulations, we
      advise a benzylpenicillin i.v. dose regimen of 75,000 IU/kg/day every 8 h (q8h),
      150,000 IU/kg/day q8h, and 200,000 IU/kg/day q6h for patients with GAs of 36 to
      37 weeks, 38 to 41 weeks, and >=42 weeks, respectively. The system-specific model
      may be used for other drugs cleared through the same pathway accelerating model
      development.

PMID- 29378711
TI  - Population Pharmacokinetics of Cefotaxime and Dosage Recommendations in Children
      with Sickle Cell Disease.
AB  - The pharmacokinetic profile of most drugs is dependent on the patient's
      covariates and may be influenced by the disease. Cefotaxime is frequently
      prescribed in pediatric patients with sickle cell disease (SCD), characterized by
      vaso-occlusive complications, chronic hemolytic anemia, and a defective
      immunological function predisposing the individual to severe infection. Data on
      the impact of the disease on the disposition of cefotaxime are missing. In the
      present study, our aims were to determine cefotaxime pharmacokinetics when
      prescribed to children with SCD for suspected or proven bacterial infection,
      identify significant covariates, and perform Monte Carlo simulations to optimize
      the drug dosage. Cefotaxime serum concentrations were measured in 78 pediatric
      SCD patients receiving cefotaxime intravenously at a daily dose of 200 mg/kg of
      body weight in three or four divided doses over 30 min. A total of 107
      concentrations were available for pharmacokinetic analysis. A population
      pharmacokinetic model was developed with NONMEM software and used for Monte Carlo
      simulations. Cefotaxime concentrations ranged from 0.05 to 103.7 mg/liter.
      Cefotaxime pharmacokinetics were best described by a one-compartment model: the
      median estimated weight-normalized volume of distribution and clearance were 0.42
      liter/kg (range, 0.2 to 1.1 liter/kg) and 0.38 liter/h/kg (range, 0.1 to 1.2
      liter/h/kg). Cefotaxime clearance increased by 22% in patients with acute chest
      syndrome. Dosing optimization, performed using EUCAST MIC susceptibility
      breakpoints, showed that a dose of 100 mg/kg/6 h should be used, depending on the
      patient's characteristics and clinical presentation, in order to reach a value of
      the percentage of time that the drug concentration exceeded the MIC under steady
      state pharmacokinetic conditions of 80% in 80% of the patients when targeting
      sensitive Gram-positive cocci and Gram-negative bacilli with MICs of 1 mg/liter
      or below.

PMID- 29378712
TI  - A 10-Year Comparative Analysis Shows that Increasing Prevalence of Rifampin
      Resistant Mycobacterium tuberculosis in China Is Associated with the Transmission
      of Strains Harboring Compensatory Mutations.
AB  - In this work, we conducted bacterial population profile studies to assess trends
      of rifampin (RIF) resistance of Mycobacterium tuberculosis isolates collected
      across China from 2005 to 2015. Totals of 273 and 269 randomly selected M.
      tuberculosis isolates from 2005 and 2015, respectively, were analyzed. The rates
      of RIF resistance (36.4%), isoniazid resistance (39.0%), and levofloxacin
      resistance (25.7%) in 2015 were significantly higher than those in 2005 (28.2%,
      30.0%, and 15.4%, respectively; P < 0.05). Genotypic data revealed 256 (95.2%)
      Beijing-type isolates in 2015, a rate significantly higher than that in 2005
      (86.4%) (P < 0.01). A higher proportion of mutations was identified within the
      rifampin resistance-determining region (RRDR) of rpoB in isolates from 2015
      (99.0%) than in 2005 isolates (85.7%, P < 0.01). In addition, a significantly
      higher proportion of RIF-resistant isolates carrying compensatory mutations was
      observed in 2015 (31.6%) than in 2005 (7.8%). Notably, the great majority of
      these compensatory mutations (91.9%) were observed in isolates that harbored a
      mutation of codon 531 of the rpoB gene. In conclusion, our data demonstrate that
      resistance to RIF, isoniazid, and levofloxacin has become significantly more
      prevalent during the past decade. In addition, the prevalence of the Beijing
      genotype significantly increased from 2005 to 2015. Notably, a significantly
      increased frequency of strains with mutations in rpoC or rpoA is observed among
      those that have codon 531 mutations, which suggests that they may be compensatory
      and may play a role in facilitating transmission.

PMID- 29378713
TI  - Enhanced Ex Vivo Plasmodium vivax Intraerythrocytic Enrichment and Maturation for
      Rapid and Sensitive Parasite Growth Assays.
AB  - Plasmodium vivax chloroquine resistance has been documented in nearly every
      region where this malaria-causing parasite is endemic. Unfortunately, P. vivax
      resistance surveillance and drug discovery are challenging due to the low
      parasitemias of patient isolates and poor parasite survival through ex vivo
      maturation that reduce the sensitivity and scalability of current P. vivax
      antimalarial assays. Using cryopreserved patient isolates from Brazil and fresh
      patient isolates from India, we established a robust enrichment method for P.
      vivax parasites. We next performed a medium screen for formulations that enhance
      ex vivo survival. Finally, we optimized an isotopic metabolic labeling assay for
      measuring P. vivax maturation and its sensitivity to antimalarials. A KCl Percoll
      density gradient enrichment method increased parasitemias from small-volume ex
      vivo isolates by an average of >40-fold. The use of Iscove's modified Dulbecco's
      medium for P. vivax ex vivo culture approximately doubled the parasite survival
      through maturation. Coupling these with [3H]hypoxanthine metabolic labeling
      permitted sensitive and robust measurements of parasite maturation, which was
      used to measure the sensitivities of Brazilian P. vivax isolates to chloroquine
      and several novel antimalarials. These techniques can be applied to rapidly and
      robustly assess the P. vivax isolate sensitivities to antimalarials for
      resistance surveillance and drug discovery.

PMID- 29378714
TI  - Pharmacokinetics of Tedizolid in an Obese Patient after Bariatric Surgery.
AB  - An obese woman was treated with oral tedizolid 200 mg once daily for
      pseudoarthrosis 10 years after Roux-en-Y bypass surgery. Total plasma peak
      concentration was 2.12 mg/liter 3 h after intake, and area under the
      concentration-time curve from 0 to 24 h (AUC0-24) was 28.3 mg/liter . h. The AUC0
      24/MIC ratio for unbound concentrations and for sensitive Staphylococcus and
      Streptococcus strains was >=10.8, higher than the target ratio of 3. These
      results support the use of tedizolid without adjustment after bariatric surgery.

PMID- 29378715
TI  - CTX-M-55-, MCR-1-, and FosA-Producing Multidrug-Resistant Escherichia coli
      Infection in a Child in France.

PMID- 29378716
TI  - Norepinephrine in Combination with Antibiotic Therapy Increases both the
      Bacterial Replication Rate and Bactericidal Activity.
AB  - We previously demonstrated that the rate and extent of an antimicrobial agent's
      bactericidal effects were coupled to the bacterial replication rate, the latter
      of which was modulated with the sodium chloride concentration. Herein, we
      describe the results from a 24-h one-compartment in vitro infection model study
      that was designed to demonstrate that an antimicrobial agent's bactericidal
      effects could be amplified when it is administered with a pharmaceutical agent
      that increases the bacterial replication rate. The antimicrobial and growth
      promoting agents selected were levofloxacin and norepinephrine, respectively. The
      challenge isolate was Escherichia coli JMI 21711R (levofloxacin MIC, 8 mg/liter).
      Within the in vitro infection model, a human levofloxacin concentration-time
      profile (half-life, 7 h) was simulated and the challenge isolate was subjected to
      an ineffective monotherapy exposure (free-drug area under the concentration-time
      curve over 24 h divided by the MIC [AUC/MIC] ratio of 6) with and without
      norepinephrine as a continuous infusion (275 mg/liter). Samples were collected
      from the model during the course of the study for bacterial density
      determinations and drug concentration assay using liquid chromatography-tandem
      mass spectrometry (LC-MS/MS). As expected, the norepinephrine and no-treatment
      control arms failed immediately, followed by the levofloxacin monotherapy arm,
      which failed slowly over time. The levofloxacin-epinephrine regimen resulted in a
      2-log10 CFU reduction in bacterial density over the first 6 to 8 h of the study,
      which was followed by regrowth of a highly levofloxacin-resistant subpopulation
      (MIC, 64 mg/liter). These data demonstrate that increasing the rate of bacterial
      replication with a pharmaceutical product in combination with antimicrobial
      therapy represents an opportunity to increase the rate and magnitude of
      bactericidal effect.

PMID- 29378717
TI  - Identification of the In Vivo Pharmacokinetics and Pharmacodynamic Driver of
      Iclaprim.
AB  - The neutropenic murine thigh infection model was used to define the
      pharmacokinetic/pharmacodynamic index linked to efficacy of iclaprim against
      Staphylococcus aureus ATCC 29213 and Staphylococcus pneumoniae ATCC 10813. The 24
      h area under the curve (AUC)/MIC index was most closely linked to efficacy for S.
      aureus (R2, 0.65), while both the 24-h AUC/MIC and the percentage of time that
      drug concentrations remain above the MIC (%T>MIC) were strongly associated with
      effect (R2, 0.86 for both parameters) for S. pneumoniae.

PMID- 29378718
TI  - Clofazimine for Treatment of Extensively Drug-Resistant Pulmonary Tuberculosis in
      China.
AB  - We performed a multicenter, prospective, randomized study to investigate the
      efficacy and safety of clofazimine (CLO) for treatment of extensively drug
      resistant tuberculosis (XDR-TB) in China. Forty-nine patients infected with XDR
      TB were randomly assigned to either the control group or the CLO group, both of
      which received 36 months of individually customized treatment. The primary
      endpoint was the time to sputum culture conversion on solid medium. Clinical
      outcomes of patients were evaluated at the time of treatment completion. Of the
      22 patients in the experimental group, 7 (31.8%) met the treatment criterion of
      "cure" and 1 (4.5%) "complete treatment," for a total of 8 (36.4%) exhibiting
      successful treatment outcomes without relapse. In the control group, 6 patients
      (22.2%) were cured and 6 (22.2%) completed treatment by the end of the study.
      Statistical analysis revealed no significant difference in successful outcome
      rates between the CLO group and the control group. The average sputum culture
      conversion time for the experimental group was 19.7 months, which was not
      statistically different from that for the control group (20.3 months; P = 0.57).
      Of the 22 patients in the CLO group, 12 (54.5%) experienced adverse events after
      starting CLO treatment. The most frequently observed adverse event was liver
      damage, with 31.8% of patients (7/22 patients) in the CLO group versus 11.1%
      (3/27 patients) in the control group exhibiting this adverse event. Our study
      demonstrates that inclusion of CLO in background treatment regimens for XDR-TB is
      of limited benefit, especially since hepatic disorders arise as major adverse
      events with CLO treatment. (This study is registered with the Chinese Clinical
      Trial Registry [ChiCTR, www.chictr.org.cn] under identifier ChiCTR1800014800.).

PMID- 29378719
TI  - Surveillance of Omadacycline Activity Tested against Clinical Isolates from the
      United States and Europe as Part of the 2016 SENTRY Antimicrobial Surveillance
      Program.
AB  - Omadacycline was tested against 21,000 bacterial isolates collected prospectively
      from medical centers in Europe and the United States during 2016. Omadacycline
      was active against Staphylococcus aureus (MIC50/MIC90, 0.12/0.25 mg/liter),
      including methicillin-resistant S. aureus (MRSA); streptococci (MIC50/MIC90,
      0.06/0.12 mg/liter), including Streptococcus pneumoniae, viridans group
      streptococci, and beta-hemolytic streptococci; Enterobacteriaceae, including
      Escherichia coli (MIC50/MIC90, 0.5/2 mg/liter); Haemophilus influenzae
      (MIC50/MIC90, 1/1 mg/liter); and Moraxella catarrhalis (MIC50/MIC90, 0.25/0.25
      mg/liter). Omadacycline merits further study in serious infections where
      resistant pathogens may be encountered.

PMID- 29378720
TI  - In Vitro Susceptibility of Clinical Staphylococcus aureus Small-Colony Variants
      to beta-Lactam and Non-beta-Lactam Antibiotics.
AB  - The Staphylococcus aureus small-colony variant (SCV) phenotype has been
      associated with relapsing and antibiotic-refractory infections. However, little
      is known about the activities of antibiotics on clinical SCVs. Here, we
      demonstrated that SCVs without detectable auxotrophies were at least as
      susceptible to most beta-lactam and non-beta-lactam antibiotics in vitro as their
      corresponding clonally identical strains with a normal phenotype. After prolonged
      incubation, a regrowth phenomenon has been observed in gradient diffusion
      inhibition zones irrespective of the strains' phenotype.

PMID- 29378721
TI  - Risk Factors and Outcomes of Endocarditis Due to Non-HACEK Gram-Negative Bacilli:
      Data from the Prospective Multicenter Italian Endocarditis Study Cohort.
AB  - The objective of this study was to investigate predisposing factors and outcomes
      of infective endocarditis (IE) caused by non-HACEK Gram-negative bacilli (GNB) in
      a contemporary multicenter cohort. Patients with IE due to GNB, prospectively
      observed in 26 Italian centers from 2004 to 2011, were analyzed. Using a case
      control design, each case was compared to three age- and sex-matched controls
      with IE due to other etiologies. Logistic regression was performed to identify
      risk factors for IE due to GNB. Factors associated with early and late mortality
      were assessed by Cox regression analysis. The study group comprised 58 patients
      with IE due to GNB. We found that Escherichia coli was the most common pathogen,
      followed by Pseudomonas aeruginosa and Klebsiella pneumoniae The genitourinary
      tract as a source of infection (odds ratio [OR], 13.59; 95% confidence interval
      [CI], 4.63 to 39.93; P < 0.001), immunosuppression (OR, 5.16; 95% CI, 1.60 to
      16.24; P = 0.006), and the presence of a cardiac implantable electronic device
      (CIED) (OR, 3.57; 95% CI, 1.55 to 8.20; P = 0.003) were factors independently
      associated with IE due to GNB. In-hospital mortality was 13.8%, and mortality
      rose to 30.6% at 1 year. A multidrug-resistant (MDR) etiology was associated with
      in-hospital mortality (hazard ratio [HR], 21.849; 95% CI, 2.672 to 178.683; P =
      0.004) and 1-year mortality (HR, 4.408; 95% CI, 1.581 to 12.287; P = 0.005). We
      conclude that the presence of a genitourinary focus, immunosuppressive therapy,
      and an indwelling CIED are factors associated with IE due to GNB. MDR etiology is
      the major determinant of in-hospital and long-term mortality.

PMID- 29378722
TI  - Importance of Site of Infection and Antibiotic Selection in the Treatment of
      Carbapenem-Resistant Pseudomonas aeruginosa Sepsis.
AB  - In a retrospective analysis of 215 patients with carbapenem-resistant Pseudomonas
      aeruginosa sepsis, we observed a significantly higher risk of mortality
      associated with respiratory tract infection (risk ratio [RR], 1.20; 95%
      confidence interval [CI], 1.04 to 1.39; P = 0.010) and lower risk with urinary
      tract infection (RR, 0.80; 95% CI, 0.71 to 0.90; P = 0.004). Aminoglycoside
      monotherapy was associated with increased mortality, even after adjusting for
      confounders (adjusted RR, 1.72; 95% CI, 1.03 to 2.85; P = 0.037), consistent
      across multiple sites of infection.

PMID- 29378724
TI  - January 29th Question.

PMID- 29378723
TI  - Emergence and Spread of kelch13 Mutations Associated with Artemisinin Resistance
      in Plasmodium falciparum Parasites in 12 Thai Provinces from 2007 to 2016.
AB  - Artemisinin-based combination therapy (ACT) is the most effective and widely used
      treatment for uncomplicated Plasmodium falciparum malaria and is a cornerstone
      for malaria control and prevention globally. Resistance to artemisinin
      derivatives has been confirmed in the Greater Mekong Subregion (GMS) and
      manifests as slow parasite clearance in patients and reduced ring stage
      susceptibility to artemisinins in survival assays. The P. falciparumkelch13 gene
      mutations associated with artemisinin-resistant parasites are now widespread in
      the GMS. We genotyped 277 samples collected during an observational study from
      2012 to 2016 from eight provinces in Thailand to identify P. falciparum kelch13
      mutations. The results were combined with previously reported genotyping results
      from Thailand to construct a map illustrating the evolution of P. falciparum
      kelch13 mutations from 2007 to 2016 in that country. Different mutant alleles
      were found in strains with different geographical origins. The artemisinin
      resistance-conferring Y493H and R539T mutations were detected mainly in eastern
      Thailand (bordering Cambodia), while P574L was found only in western Thailand and
      R561H only in northwestern Thailand. The C580Y mutation was found across the
      entire country and was nearing fixation along the Thai-Cambodia border. Overall,
      the prevalence of artemisinin resistance mutations increased over the last 10
      years across Thailand, especially along the Thai-Cambodia border. Molecular
      surveillance and therapeutic efficacy monitoring should be intensified in the
      region to further assess the extent and spread of artemisinin resistance.

PMID- 29378725
TI  - Variability of PD-L1 expression in mastocytosis.
AB  - Mastocytosis is a rare disease with heterogeneous clinical manifestations and few
      effective therapies. Programmed death-1 (PD-1) and its ligands (PD-L1 and PD-L2)
      protect tissues from immune-mediated damage and permit tumors to evade immune
      destruction. Therapeutic antibodies against PD-1 and PD-L1 are effective in the
      treatment of a variety of neoplasms. In the present study, we sought to
      systematically analyze expression of PD-1 and PD-L1 in a large number of patients
      with mastocytosis using immunohistochemistry and multiplex fluorescence staining.
      PD-L1 showed membrane staining of neoplastic mast cells (MCs) in 77% of systemic
      mastocytosis (SM) cases including 3 of 3 patients with MC leukemia, 2 of 2 with
      aggressive SM, 1 of 2 with smoldering SM, 3 of 4 with indolent SM, and 9 of 12
      with SM with an associated hematologic neoplasm (SM component only). Ninety-two
      percent (23 of 25) of cutaneous mastocytosis (CM) cases and 1 of 2 with
      myelomastocytic leukemia expressed PD-L1, with no expression found in 15
      healthy/reactive marrows, 18 myelodysplastic syndromes (MDSs), 16
      myeloproliferative neoplasms (MPNs), 5 MDS/MPNs, and 3 monoclonal MC activation
      syndromes. Variable PD-L1 expression was observed between and within samples,
      with PD-L1 staining of MCs ranging from 10% to 100% (mean, 50%). PD-1 dimly
      stained 4 of 27 CM cases (15%), with no expression in SM or other neoplasms
      tested; PD-1 staining of MCs ranged from 20% to 50% (mean, 27%). These results
      provide support for the expression of PD-L1 in SM and CM, and PD-1 expression in
      CM. These data support the exploration of agents with anti-PD-L1 activity in
      patients with advanced mastocytosis.

PMID- 29378726
TI  - Comparative effectiveness of direct oral anticoagulants and warfarin in patients
      with cancer and atrial fibrillation.
AB  - Randomized clinical trials comparing direct oral anticoagulants (DOACs) to
      warfarin in cancer patients have not been performed. We evaluated the
      effectiveness and associated risk of DOACs vs warfarin, as well as comparisons of
      DOACs, in a large population of cancer patients with nonvalvular atrial
      fibrillation (AF). Using the MarketScan databases, we identified 16 096 AF
      patients (mean age, 74 years) initiating oral anticoagulant and being actively
      treated for cancer between 2010 and 2014. Anticoagulant users were matched by
      age, sex, enrollment date, and drug initiation date. Study end points were
      identified with diagnostic codes and included ischemic stroke, severe bleeding,
      other bleeding, and venous thromboembolism (VTE). Cox regression was used to
      estimate associations of anticoagulants with study end points. Compared with
      warfarin, rates of bleeding (hazard ratio [95% confidence interval]) were similar
      in rivaroxaban (1.09 [0.79, 1.39]) and dabigatran (0.96 [0.72, 1.27]) users,
      whereas apixaban users experienced lower rates (0.37 [0.17, 0.79]). Rates of
      ischemic stroke did not differ among anticoagulant users. Compared with warfarin,
      rate of VTE (hazard ratio [95% confidence interval]) was lower among rivaroxaban
      (0.51 [0.41, 0.63]), dabigatran (0.28 [0.21, 0.38]), and apixaban (0.14 [0.07,
      0.32]) users. In head-to-head comparisons among DOACs, dabigatran users had lower
      rates of VTE than rivaroxaban users; apixaban users had lower rates of VTE and
      severe bleeding than rivaroxaban users. In this population of patients with AF
      and cancer, DOAC users experienced lower or similar rates of bleeding and stroke
      compared with warfarin users, and a lower rate of incident VTE.

PMID- 29378727
TI  - Prevalence and characteristics of ocular pain in non-infectious uveitis: a
      quality of life study.
AB  - BACKGROUND/AIM: To survey the frequency, character, severity and impact of ocular
      pain on quality of life in adult patients with non-infectious uveitis (NIU).
      METHODS: This patient-requested cross-sectional survey study describes the
      results of three self-administered questionnaires (the National Eye Institute
      Visual Function Questionnaire, the 36-Item Short Form Health Survey (SF-36) and
      the McGill Pain Questionnaire Dutch Language Version) from 147 patients with NIUs
      from a university-based tertiary referral centre in Utrecht. RESULTS: The mean
      Visual Function Questionnaire (VFQ) Ocular Pain Score of all patients with NIU
      was 72 (+/-24), which is significantly lower than an ocular disease-free
      reference group (90+/-15, P<0.0001), indicating more ocular pain. This was true
      for all types of NIU, regardless of the localisation: although Ocular Pain Scores
      were lower in patients with anterior uveitis (AU) compared with patients with non
      AU (mean 62 (+/-24) vs 74 (+/-24), P=0.04), patients with non-AU still scored
      substantially lower than the reference group that had no ocular history
      (P<0.0001). Patients with NIU also scored significantly lower on all other VFQ
      subscales as well as on the SF-36 subscales 'Role Limitations due to physical
      problems', 'Vitality', 'General health' and 'Bodily Pain' compared with controls.
      The VFQ Ocular Pain subscale correlated with other quality of life subscales
      (both VFQ-25 and SF-36), indicating a relationship between pain and quality of
      life. CONCLUSION: This study shows that ocular pain is highly prevalent in
      patients with NIU, regardless of the localisation. Furthermore, ocular pain has
      an impact on quality of life.

PMID- 29378728
TI  - Combined treatment of primary vitreoretinal lymphomas significantly prolongs the
      time to first relapse.
AB  - BACKGROUND: Vitreoretinal lymphomas belong to the family of central nervous
      system (CNS) lymphomas. The optimal approach for the treatment of isolated
      primary vitreoretinal lymphoma is unclear because of the lack of large
      comparative clinical series. Combination of intravitreal and systemic
      chemotherapy is recommended in many reports. The aim of our retrospective study
      was to compare the survival rate and prognosis of patients with vitreoretinal
      lymphoma with and without CNS involvement. METHODS: Twenty patients with
      vitreoretinal lymphomas were observed between the years 2004and2016, 10 patients
      with primary vitreoretinal lymphoma and 10 with primary CNS lymphoma. To compare
      survival rates, we included 53 patients diagnosed with primary CNS lymphoma
      without vitreoretinal involvement between the years 2002and2011 from our haemato
      oncology department. RESULTS: The 5-year survival rate was estimated 71% in
      patients with vitreoretinal lymphoma in our observation. Significantly longer 5
      year overall survival (P?0.01) was observed in patients with vitreoretinal
      lymphoma compared with patients with primary CNS lymphoma without vitreoretinal
      involvement. Progression-free survival was almost equal in both groups of
      patients with primary vitreoretinal lymphoma and primary CNS lymphoma (P=0.363).
      The relapse of lymphoma was frequent (50%-60%) with the median time to first
      relapse of 31 months. Combined treatment (local and systemic) in patients without
      CNS involvement significantly prolonged progression-free survival in our study
      (P?0.05). CONCLUSION: Combined treatment of primary vitreoretinal lymphoma
      significantly delays the relapse of lymphoma compared with local therapy alone.
      Intraocular involvement brings significant positive prognostic value when overall
      survival is compared.

PMID- 29378729
TI  - Atrial Fibrillation and Cause-Specific Risks of Pulmonary Embolism and Ischemic
      Stroke.
AB  - BACKGROUND: Atrial fibrillation (AF) is a well-established risk factor for
      ischemic stroke (IS). Emerging evidence also indicates an association between AF
      and pulmonary embolism (PE). Because IS may potentially mediate the observed risk
      of PE in AF, we aimed to assess the impact of AF on the cause-specific risks of
      PE and IS in a large cohort recruited from the general population. METHODS AND
      RESULTS: We observed 29 842 participants from 3 surveys of the Tromso study
      (inclusion in 1994-1995, 2001-2002, and 2007-2008) to the end of 2012. Incident
      events of AF, IS, and PE during follow-up were recorded, and information on
      potential confounders was obtained at baseline. Cox regression models, with AF as
      a time-dependent variable, were used to calculate cause-specific hazard ratios
      (HRs) with 95% confidence intervals (CIs) for PE and IS. There were 2067
      participants diagnosed as having AF, 296 with PE and 1164 with IS, during a
      median of 17.6 years of follow-up. The risks of PE (HR, 10.88; 95% CI, 6.23
      18.89) and IS (HR, 6.16; 95% CI, 4.47-8.48) were substantially increased during
      the first 6 months after AF diagnosis, with crude incidence rates of 18.5 per
      1000 person-years for PE and 52.8 per 1000 person-years for IS. The risk
      estimates remained elevated for both PE (HR, 1.72; 95% CI, 1.10-2.71) and IS (HR,
      2.45; 95% CI, 2.05-2.92) throughout the study period. CONCLUSIONS: AF was
      associated with increased cause-specific risks of both PE and IS. Our findings
      infer that the risk of PE in AF is not explained by intermediate IS.

PMID- 29378730
TI  - Evidence for Pressure-Independent Sympathetic Modulation of Central Pulse Wave
      Velocity.
AB  - BACKGROUND: Whether the sympathetic nervous system can directly alter central
      aortic stiffness remains controversial, mainly because of the difficulty in
      experimentally augmenting peripheral vasoconstrictor activity without changing
      blood pressure. METHODS AND RESULTS: To address this limitation, we utilized low
      level cardiopulmonary baroreflex loading and unloading shown previously to alter
      sympathetic outflow without evoking parallel hemodynamic modulation. Blood
      pressure and carotid-femoral aortic pulse wave velocity (cf-PWV) were measured in
      32 healthy participants (24+/-2 years; women: n=15) before and during 12-minute
      applications of low-level lower body negative pressure; -7 mm Hg) and lower body
      positive pressure; +7 mm Hg), applied in a random order. Fibular nerve
      microneurography was used to collect muscle sympathetic nerve activity (MSNA) in
      a subset (n=8) to confirm peripheral sympathetic responses. During lower body
      negative pressure, heart rate, blood pressure, stroke volume, cardiac output, and
      total peripheral resistance were not statistically different (all P>0.05); MSNA
      burst frequency (+15%; P=0.007), total MSNA (+44%; P=0.006), and cf-PWV (?+0.3+/
      0.2 m/s; P<0.001) increased. In total, 28 (88%) of participants observed an
      increase in cf-PWV greater than the baseline typical error of measurement. During
      lower body positive pressure, heart rate, stroke volume, cardiac output, and
      total peripheral resistance were not statistically different (all P>0.05), though
      blood pressure increased (P<0.05) and pulse pressure decreased (P=0.01); MSNA
      burst frequency (-4%; P=0.37), total MSNA (-7%; P=0.89), and cf-PWV (?0.0+/-0.2
      m/s; P=0.68) were not statistically different. CONCLUSIONS: These findings
      provide evidence that acute elevations in peripheral sympathetic activity can
      increase central aortic PWV in young participants independent of a change in
      distending or pulsatile blood pressure or heart rate.

PMID- 29378731
TI  - Neuronal PirB Upregulated in Cerebral Ischemia Acts as an Attractive Theranostic
      Target for Ischemic Stroke.
AB  - BACKGROUND: Ischemic stroke is a complex disease with multiple etiologies and
      clinical manifestations. Paired immunoglobulin-like receptor B (PirB), which is
      originally thought to function exclusively in the immune system, is now also
      known to be expressed by neurons. A growing number of studies indicate that PirB
      can inhibit neurite outgrowth and restrict neuronal plasticity. The aim of the
      study is to investigate whether PirB can be an attractive theranostic target for
      ischemic stroke. METHODS AND RESULTS: First, we investigated the spatial-temporal
      expression of PirB in multiple ischemic stroke models, including transient middle
      cerebral artery occlusion, photothrombotic cerebral cortex ischemia, and the
      neuronal oxygen glucose deprivation model. Then, anti-PirB immunoliposome
      nanoprobe was developed by thin-film hydration method and investigated its
      specific targeting in vitro and in vivo. Finally, soluble PirB ectodomain (sPirB)
      protein delivered by polyethylene glycol-modified nanoliposome was used as a
      therapeutic reagent for ischemic stroke by blocking PirB binding to its
      endogenous ligands. These results showed that PirB was significantly upregulated
      after cerebral ischemic injury in ischemic stroke models. Anti-PirB
      immunoliposome nanoprobe was successfully developed and specifically bound to
      PirB in vitro. There was accumulation of anti-PirB immunoliposome nanoprobe in
      the ischemic hemisphere in vivo. Soluble PirB ectodomains remarkably improved
      ischemic stroke model recovery by liposomal delivery system. CONCLUSIONS: These
      data indicated that PirB was a significant element in the pathological process of
      cerebral ischemia. Therefore, PirB may act as a novel theranostic target for
      ischemic stroke.

PMID- 29378732
TI  - Association of Hemoglobin Concentration and Its Change With Cardiovascular and
      All-Cause Mortality.
AB  - BACKGROUND: Anemia is thought to increase mortality risks, but the effects of
      high hemoglobin concentration on survival are unclear. The effect of change in
      hemoglobin concentrations on survival in the general population is also unknown.
      This study aimed to examine the effect of hemoglobin concentrations and their
      changes on cardiovascular and all-cause mortality risks. METHODS AND RESULTS: We
      retrospectively analyzed a cohort from the NHIS-HEALS (National Health Insurance
      Service-National Health Screening Cohort) database, including 170 078 men and 122
      116 women without cardiovascular diseases, aged >40 years at baseline, with
      hemoglobin concentrations available for both first and second health
      examinations. We assessed 2 independent variables: "One-time" hemoglobin
      concentrations and changes in hemoglobin from first to second examination.
      Participants were followed up for a median of 8 years to determine mortality
      related to myocardial infarction, stroke, all cardiovascular diseases, and all
      causes. Hemoglobin concentrations showed a U- or J-shaped association with
      cardiovascular and all-cause mortality after adjusting for cardiovascular risk
      factors. When anemic men achieved normal hemoglobin concentrations, the all-cause
      mortality risk decreased, with an adjusted hazard ratio of 0.67 (95% confidence
      interval, 0.59-0.77), in comparison with those whose anemia persisted. Both
      increases and decreases of hemoglobin concentration outside the normal range
      elevated all-cause mortality risk (adjusted hazard ratio: 1.39 [95% confidence
      interval, 1.28-1.49] and 1.10 [95% confidence interval, 1.01-1.20],
      respectively), compared with persistent normal hemoglobin concentrations. The
      trend was similar in women but was less significant. CONCLUSIONS: Low or high
      hemoglobin concentrations were associated with elevated cardiovascular and all
      cause mortality. Reaching and maintaining hemoglobin concentrations within the
      normal range correlated with decreased all-cause mortality.

PMID- 29378734
TI  - Myocardial Injury in Patients With Sepsis and Its Association With Long-Term
      Outcome.
AB  - BACKGROUND: Sepsis is frequently complicated by the release of cardiac troponin,
      but the clinical significance of this myocardial injury remains unclear. We
      studied the associations between troponin release during sepsis and 1-year
      outcomes. METHODS AND RESULTS: We enrolled consecutive patients with sepsis in 2
      Dutch intensive care units between 2011 and 2013. Subjects with a clinically
      apparent cause of troponin release were excluded. High-sensitivity cardiac
      troponin I (hs-cTnI) concentration in plasma was measured daily during the first
      4 intensive care unit days, and multivariable Cox regression analysis was used to
      model its association with 1-year mortality while adjusting for confounding. In
      addition, we studied cardiovascular morbidity occurring during the first year
      after hospital discharge. Among 1258 patients presenting with sepsis, 1124 (89%)
      were eligible for study inclusion. Hs-cTnI concentrations were elevated in 673
      (60%) subjects on day 1, and 755 (67%) ever had elevated levels in the first 4
      days. Cox regression analysis revealed that high hs-cTnI concentrations were
      associated with increased death rates during the first 14 days (adjusted hazard
      ratio, 1.72; 95% confidence interval, 1.14-2.59 and hazard ratio, 1.70; 95%
      confidence interval, 1.10-2.62 for hs-cTnI concentrations of 100-500 and >500
      ng/L, respectively) but not thereafter. Furthermore, elevated hs-cTnI levels were
      associated with the development of cardiovascular disease among 200 hospital
      survivors who were analyzed for this end point (adjusted subdistribution hazard
      ratio, 1.25; 95% confidence interval, 1.04-1.50). CONCLUSIONS: Myocardial injury
      occurs in the majority of patients with sepsis and is independently associated
      with early-but not late-mortality, as well as postdischarge cardiovascular
      morbidity.

PMID- 29378735
TI  - New onset diabetes after nivolumab treatment.
AB  - The authors describe a case of a life-threatening diabetic emergency 25 days
      after initiation of nivolumab (3 mg/kg) for stage 4 lung adenocarcinoma. She was
      admitted to the emergency department, with hyperglycaemia-related signs and
      symptoms, such as polyuria, polydipsia, weight loss, confusion, asthenia,
      dehydration, hypotension and Kussmaul respiratory pattern. Her body mass index
      was 21.9 kg/m2 and she did not show acanthosis nigricans. Arterial blood gas
      determination revealed high anion gap metabolic acidaemia and blood tests showed
      hyperglycaemia (1060 mg/dL), hyperketonaemia (beta-hydroxybutyrate: 6.6 mmol/dL),
      elevated total serum osmolality (389 mOsm/kg), low serum and urinary C-peptide
      and positive antiglutamic acid decarboxylase antibodies. Since nivolumab was
      initiated a few days before, and due to its known immune-mediated endocrine
      adverse events, we assumed the diagnosis of new onset immune-mediated type 1
      diabetes mellitus. After prompt and adequate treatment of diabetic
      ketoacidosis/hyperosmolar hyperglycaemic state, she was discharged improved on
      multiple daily injections of insulin.

PMID- 29378736
TI  - Intravascular lymphoma presenting with postural hypotension.
AB  - An 84-year-old woman presented with severe postural hypotension. Further
      assessment revealed weight loss, fatigue and fever at night. On examination, she
      had bilateral skin lesions on the inner thighs and skin biopsy revealed
      intravascular high grade B cell lymphoma. This was successfully treated with
      curative chemotherapy. The cause of the postural hypotension in this case was
      felt likely to be autonomic neuropathy caused by neurovascular infiltration by
      intravascular lymphoma. Treatment of the lymphoma has resolved the postural
      hypotension, although some symptoms of postural instability persist.

PMID- 29378733
TI  - Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with
      Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined
      Classification.
AB  - Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of
      reliable predictors of response to neoadjuvant chemotherapy (NACT). For this
      purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a
      cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel
      (TCb).Methods: Patients with TNBC were accrued in a nonrandomized trial of
      neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was
      evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and
      residual cancer burden by Symmans and colleagues. Lehmann's subtyping was
      performed using the TNBCtype online tool from RNAseq data, and germline
      sequencing of a panel of seven DNA damage repair genes was conducted.Results:
      Ninety-four out of the 121 patients enrolled in the trial had RNAseq available.
      The overall pCR rate was 44.7%. Lehmann subtype distribution was 34.0% BL1, 20.2%
      BL2, 23.4% M, 14.9% LAR, and 7.4% were classified as ER+. Response to NACT with
      TCb was significantly associated with Lehmann subtype (P = 0.027), even in
      multivariate analysis including tumor size and nodal involvement, with BL1
      patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M
      (36.4%), and LAR (21.4%). BL1 was associated with a significant younger age at
      diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30%
      were BL1, 40% were BL2, and 30% were M.Conclusions: TNBCtype-4 is associated with
      significantly different pCR rates for the different subtypes, with BL1 and LAR
      displaying the best and worse responses to NACT, respectively. Clin Cancer Res;
      24(8); 1845-52. (c)2018 AACR.

PMID- 29378737
TI  - Cryptosporidium diagnosed on endoscopic biopsy in a paediatric patient with
      inflammatory bowel disease.
AB  - Cryptosporidium, a parasitic infection commonly associated with diarrhoea, may be
      difficult to differentiate from a flare in patients with inflammatory bowel
      disease and can lead to unnecessary therapy and increase in morbidity and
      mortality. We report the case of a paediatric patient who had substantial stool
      output requiring significant fluid resuscitation and who was later diagnosed with
      cryptosporidium on endoscopic biopsy. Diagnostic work up for cryptosporidium
      should be strongly considered when a patient presents with a flare involving
      massive stool output.

PMID- 29378738
TI  - Pott's disease associated with large and multiple abscesses in a 30-year-old
      migrant from Chad.

PMID- 29378744
TI  - Commentary.

PMID- 29378742
TI  - Restricted IgG-Kappa and Free Alpha-Heavy-Chain Bands in an Asymptomatic 62-Year
      Old Man.

PMID- 29378741
TI  - Chronic incomplete non-puerperal uterine inversion due to huge submucous fibroid:
      diagnosis and management.

PMID- 29378747
TI  - Persistent Increase in Alkaline Phosphatase.

PMID- 29378745
TI  - A Newborn with Hypothermia and Hyperammonemia.

PMID- 29378746
TI  - Atypical Pseudohyponatremia.

PMID- 29378739
TI  - Segmental dilatation of small bowel presenting with severe anaemia: a diagnostic
      puzzle.
AB  - A 7-year-old boy presented to Paediatric outpatient with worsening lethargy and
      tiredness. On examination he had extreme pallor. Blood investigations confirmed
      severe iron deficiency anaemia. He was started on iron supplements and received
      blood transfusion. However, the response to iron treatment was suboptimal, he
      therefore underwent extensive workup for the cause of iron deficiency anaemia.
      The barium meal showed dilated segments of ileum with two distal stenoses. The
      surgical resection of the involved segment was performed with end to end
      anastamosis. Histology of the resected segment was inconclusive of inflammatory
      bowel disease, malignancy or vascular malformation. The child has remained well
      since surgery with no further blood transfusion or iron therapy.

PMID- 29378748
TI  - A Shark-Human Chimera.

PMID- 29378740
TI  - Fuchs syndrome: a case of fever, mucositis and conjunctivitis.

PMID- 29378749
TI  - Group Work.
AB  - Science, technology, engineering, and mathematics faculty are increasingly
      incorporating both formal and informal group work in their courses. Implementing
      group work can be improved by an understanding of the extensive body of
      educational research studies on this topic. This essay describes an online,
      evidence-based teaching guide published by CBE-Life Sciences Education (LSE). The
      guide provides a tour of research studies and resources related to group work
      (including many articles from LSE). Instructors who are new to group work, as
      well as instructors who have experienced difficulties in implementing group work,
      may value the condensed summaries of key research findings. These summaries are
      organized by teaching challenges, and actionable advice is provided in a
      checklist for instructors. Education researchers may value the inclusion of
      empirical studies, key reviews, and meta-analyses of group-work studies. In
      addition to describing key features of the guide, this essay also identifies
      areas in which further empirical studies are warranted.

PMID- 29378754
TI  - Repurposing Metformin for Cardiovascular Disease.

PMID- 29378758
TI  - Sham-Controlled Trial Questions Benefit of Stents for Stable Angina.

PMID- 29378755
TI  - The Cardiac Troponin Renal Disease Diagnostic Conundrum: Past, Present, and
      Future.

PMID- 29378756
TI  - Lymphangiogenesis in Chronic Rejection and Coronary Allograft Vasculopathy: An
      Emerging Diagnostic and Therapeutic Target?

PMID- 29378751
TI  - Scientific Presenting: Using Evidence-Based Classroom Practices to Deliver
      Effective Conference Presentations.
AB  - Scientists and educators travel great distances, spend significant time, and
      dedicate substantial financial resources to present at conferences. This
      highlights the value placed on conference interactions. Despite the importance of
      conferences, very little has been studied about what is learned from the
      presentations and how presenters can effectively achieve their goals. This essay
      identifies several challenges presenters face when giving conference
      presentations and discusses how presenters can use the tenets of scientific
      teaching to meet these challenges. We ask presenters the following questions: How
      do you engage the audience and promote learning during a presentation? How do you
      create an environment that is inclusive for all in attendance? How do you gather
      feedback from the professional community that will help to further advance your
      research? These questions target three broad goals that stem from the scientific
      teaching framework and that we propose are of great importance at conferences:
      learning, equity, and improvement. Using a backward design approach, we discuss
      how the lens of scientific teaching and the use of specific active-learning
      strategies can enhance presentations, improve their utility, and ensure that a
      presentation is broadly accessible to all audience members.

PMID- 29378750
TI  - Trust, Growth Mindset, and Student Commitment to Active Learning in a College
      Science Course.
AB  - There is growing consensus regarding the effectiveness of active-learning
      pedagogies in college science courses. Less is known about ways that student
      level factors contribute to positive outcomes in these contexts. The present
      study examines students' (N = 245) trust in the instructor-defined as perceptions
      of their instructor's understanding, acceptance, and care-and students' attitudes
      toward learning within an anatomy and physiology course featuring active
      learning. Analyses indicate that student trust of instructor and students' views
      of their own intelligence are both associated with student commitment to, and
      engagement in, active learning. Student-reported trust of the instructor
      corresponded to final grade, while students' views of their own intelligence did
      not. In an active-learning context in which students are more fully engaged in
      the learning process, student trust of the instructor was an important
      contributor to desired student outcomes.

PMID- 29378760
TI  - Unique ECG During Sinus Rhythm in a Patient With a Postmyocardial Infarction
      Sustained Ventricular Tachycardia.

PMID- 29378759
TI  - Highlights From the Circulation Family of Journals.

PMID- 29378753
TI  - Exercise and Hypertrophic Cardiomyopathy: Time for a Change of Heart.

PMID- 29378743
TI  - Commentary.

PMID- 29378752
TI  - Benefit-Cost Analysis of Undergraduate Education Programs: An Example Analysis of
      the Freshman Research Initiative.
AB  - Institutions and administrators regularly have to make difficult choices about
      how best to invest resources to serve students. Yet economic evaluation, or the
      systematic analysis of the relationship between costs and outcomes of a program
      or policy, is relatively uncommon in higher education. This type of evaluation
      can be an important tool for decision makers considering questions of resource
      allocation. Our purpose with this essay is to describe methods for conducting one
      type of economic evaluation, a benefit-cost analysis (BCA), using an example of
      an existing undergraduate education program, the Freshman Research Initiative
      (FRI) at the University of Texas Austin. Our aim is twofold: to demonstrate how
      to apply BCA methodologies to evaluate an education program and to conduct an
      economic evaluation of FRI in particular. We explain the steps of BCA, including
      assessment of costs and benefits, estimation of the benefit-cost ratio, and
      analysis of uncertainty. We conclude that the university's investment in FRI
      generates a positive return for students in the form of increased future earning
      potential.

PMID- 29378757
TI  - Systemic Right Ventricle in Adults With Congenital Heart Disease: Anatomic and
      Phenotypic Spectrum and Current Approach to Management.
AB  - The systemic right ventricle (SRV) is commonly encountered in congenital heart
      disease representing a distinctly different model in terms of its anatomic
      spectrum, adaptation, clinical phenotype, and variable, but overall guarded
      prognosis. The most common clinical scenarios where an SRV is encountered are
      complete transposition of the great arteries with previous atrial switch repair,
      congenitally corrected transposition of the great arteries, double inlet right
      ventricle mostly with previous Fontan palliation, and hypoplastic left heart
      syndrome palliated with the Norwood-Fontan protocol. The reasons for the guarded
      prognosis of the SRV in comparison with the systemic left ventricle are
      multifactorial, including distinct fibromuscular architecture, shape and
      function, coronary artery supply mismatch, intrinsic abnormalities of the
      tricuspid valve, intrinsic or acquired conduction abnormalities, and varied SRV
      adaptation to pressure or volume overload. Management of the SRV remains an
      ongoing challenge because SRV dysfunction has implications on short- and long
      term outcomes for all patients irrespective of underlying cardiac morphology. SRV
      dysfunction can be subclinical, underscoring the need for tertiary follow-up and
      timely management of target hemodynamic lesions. Catheter interventions and
      surgery have an established role in selected patients. Cardiac resynchronization
      therapy is increasingly used, whereas pharmacological therapy is largely
      empirical. Mechanical assist device and heart transplantation remain options in
      end-stage heart failure when other management strategies have been exhausted. The
      present report focuses on the SRV with its pathological subtypes,
      pathophysiology, clinical features, current management strategies, and long-term
      sequelae. Although our article touches on issues applicable to neonates and
      children, its main focus is on adults with SRV.

PMID- 29378761
TI  - Does Sport Participation Worsen the Clinical Course of Hypertrophic
      Cardiomyopathy? Clinical Outcome of Hypertrophic Cardiomyopathy in Athletes.

PMID- 29378762
TI  - High Prevalence of Occult Heart Failure With Preserved Ejection Fraction Among
      Patients With Atrial Fibrillation and Dyspnea.

PMID- 29378763
TI  - Letter by Jin-shan and Xue-bin Regarding Article, "Prevalence of Subclinical
      Coronary Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic
      Risk Profile".

PMID- 29378764
TI  - Letter by Harrell et al Regarding Article, "Prevalence of Subclinical Coronary
      Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk
      Profile".

PMID- 29378765
TI  - Letter by Schmermund Regarding Article, "Prevalence of Subclinical Coronary
      Artery Disease in Masters Endurance Athletes With a Low Atherosclerotic Risk
      Profile".

PMID- 29378766
TI  - Response by Merghani et al to Letters Regarding Article, "Prevalence of
      Subclinical Coronary Artery Disease in Masters Endurance Athletes With a Low
      Atherosclerotic Risk Profile".

PMID- 29378767
TI  - Perilipin 5 Deletion Unmasks an Endoplasmic Reticulum Stress-Fibroblast Growth
      Factor 21 Axis in Skeletal Muscle.
AB  - Lipid droplets (LDs) are critical for the regulation of lipid metabolism, and
      dysregulated lipid metabolism contributes to the pathogenesis of several
      diseases, including type 2 diabetes. We generated mice with muscle-specific
      deletion of the LD-associated protein perilipin 5 (PLIN5, Plin5MKO ) and
      investigated PLIN5's role in regulating skeletal muscle lipid metabolism,
      intracellular signaling, and whole-body metabolic homeostasis. High-fat feeding
      induced changes in muscle lipid metabolism of Plin5MKO mice, which included
      increased fatty acid oxidation and oxidative stress but, surprisingly, a
      reduction in inflammation and endoplasmic reticulum (ER) stress. These muscle
      specific effects were accompanied by whole-body glucose intolerance, adipose
      tissue insulin resistance, and reduced circulating insulin and C-peptide levels
      in Plin5MKO mice. This coincided with reduced secretion of fibroblast growth
      factor 21 (FGF21) from skeletal muscle and liver, resulting in reduced
      circulating FGF21. Intriguingly, muscle-secreted factors from Plin5MKO , but not
      wild-type mice, reduced hepatocyte FGF21 secretion. Exogenous correction of FGF21
      levels restored glycemic control and insulin secretion in Plin5MKO mice. These
      results show that changes in lipid metabolism resulting from PLIN5 deletion
      reduce ER stress in muscle, decrease FGF21 production by muscle and liver, and
      impair glycemic control. Further, these studies highlight the importance for
      muscle-liver cross talk in metabolic regulation.

PMID- 29378768
TI  - Chromothripsis and ring chromosome 22: a paradigm of genomic complexity in the
      Phelan-McDermid syndrome (22q13 deletion syndrome).
AB  - INTRODUCTION: Phelan-McDermid syndrome (PMS) is caused by SHANK3
      haploinsufficiency. Its wide phenotypic variation is attributed partly to the
      type and size of 22q13 genomic lesion (deletion, unbalanced translocation, ring
      chromosome), partly to additional undefined factors. We investigated a child with
      severe global neurodevelopmental delay (NDD) compatible with her distal 22q13
      deletion, complicated by bilateral perisylvian polymicrogyria (BPP) and
      urticarial rashes, unreported in PMS. METHODS: Following the cytogenetic and
      array-comparative genomic hybridization (CGH) detection of a r(22) with SHANK3
      deletion and two upstream duplications, whole-genome sequencing (WGS) in blood
      and whole-exome sequencing (WES) in blood and saliva were performed to highlight
      potential chromothripsis/chromoanagenesis events and any possible BPP-associated
      variants, even in low-level mosaicism. RESULTS: WGS confirmed the deletion and
      highlighted inversion and displaced order of eight fragments, three of them
      duplicated. The microhomology-mediated insertion of partial Alu-elements at one
      breakpoint junction disrupted the topological associating domain joining NFAM1 to
      the transcriptional coregulator TCF20. WES failed to detect BPP-associated
      variants. CONCLUSIONS: Although we were unable to highlight the molecular basis
      of BPP, our data suggest that SHANK3 haploinsufficiency and TCF20 misregulation,
      both associated with intellectual disability, contributed to the patient's NDD,
      while NFAM1 interruption likely caused her skin rashes, as previously reported.
      We provide the first example of chromoanasynthesis in a constitutional ring
      chromosome and reinforce the growing evidence that chromosomal rearrangements may
      be more complex than estimated by conventional diagnostic approaches and affect
      the phenotype by global alteration of the topological chromatin organisation
      rather than simply by deletion or duplication of dosage-sensitive genes.

PMID- 29378769
TI  - Neuropsychiatric and metabolic aspects of dopaminergic therapy: perspectives from
      an endocrinologist and a psychiatrist.
AB  - The dopaminergic treatment represents the primary treatment in prolactinomas,
      which are the most common pituitary adenomas and account for about 40% of all
      pituitary tumours with an annual incidence of six to ten cases per million
      population. The dopaminergic treatment includes ergot and non-ergot derivatives
      with high affinity for the dopamine receptors D1 or/and D2. Through the
      activation of the dopaminergic pathway on pituitary lactotrophs, the dopamine
      agonists inhibit the prolactin synthesis and secretion, therefore normalizing the
      prolactin levels and restoring eugonadism, but they also lead to tumour
      shrinkage. Treatment with dopamine agonists has been associated - apart from the
      common side effects such as gastrointestinal symptoms, dizziness and hypotension 
      with neuropsychiatric side effects such as impulse control disorders (e.g.
      pathological gambling, compulsive shopping, hypersexuality and binge eating) and
      also with behavioral changes from low mood, irritability and verbal
      aggressiveness up to psychotic and manic symptoms and paranoid delusions not only
      in patients with prolactinomas but also in patients with Parkinson's disease and
      restless leg syndrome. They usually have de novo onset after initiation of the
      dopaminergic treatment and have been mainly reported in patients with Parkinson's
      disease, who are being treated with higher doses of dopamine agonists. Moreover,
      dopamine and prolactin seem to play an essential role in the metabolic pathway.
      Patients with hyperprolactinemia tend to have increased body weight and an
      altered metabolic profile with hyperinsulinemia and increased prevalence of
      diabetes mellitus in comparison to healthy individuals and patients with non
      functioning pituitary adenomas. Treatment with dopamine agonists in these
      patients in short-term studies seems to lead to weight loss and amelioration of
      the metabolic changes. Together these observations provide evidence that dopamine
      and prolactin have a crucial role both in the regard and metabolic system,
      findings that merit further investigation in long-term studies.

PMID- 29378770
TI  - Management of Membranous Nephropathy in the PLA2R Era.

PMID- 29378771
TI  - Anti-insulin-like growth factor therapy in breast cancer.
AB  - Early preclinical and population data suggested a role for the type I insulin
      like growth factor receptor (IGF1R) in the regulation of breast cancer growth and
      survival. To target this pathway, multiple monoclonal antibodies and tyrosine
      kinase inhibitors were developed and tested in clinical trials. While some of the
      early clinical trials suggested a benefit for these drugs, none of the attempts
      showed improved outcomes when compared to conventional therapy. This failure of
      the IGF1R inhibitors was pronounced in breast cancer; multiple trials testing
      IGF1R inhibition in estrogen receptor-positive breast cancer were conducted, none
      showed benefit. This review will evaluate the rationale for IGF1R inhibition,
      discuss results of the clinical trials and suggest a path forward.

PMID- 29378773
TI  - Mindful choice of endoscopic resection for large colorectal lesions.

PMID- 29378772
TI  - Circadian rhythms in mitochondrial respiration.
AB  - Many physiological processes are regulated with a 24-h periodicity to anticipate
      the environmental changes of daytime to nighttime and vice versa. These 24-h
      regulations, commonly termed circadian rhythms, among others control the sleep
      wake cycle, locomotor activity and preparation for food availability during the
      active phase (daytime for humans and nighttime for nocturnal animals). Disturbing
      circadian rhythms at the organ or whole-body level by social jetlag or shift
      work, increases the risk to develop chronic metabolic diseases such as type 2
      diabetes mellitus. The molecular basis of this risk is a topic of increasing
      interest. Mitochondria are essential organelles that produce the majority of
      energy in eukaryotes by converting lipids and carbohydrates into ATP through
      oxidative phosphorylation. To adapt to the ever-changing environment,
      mitochondria are highly dynamic in form and function and a loss of this
      flexibility is linked to metabolic diseases. Interestingly, recent studies have
      indicated that changes in mitochondrial morphology (i.e., fusion and fission) as
      well as generation of new mitochondria are dependent on a viable circadian clock.
      In addition, fission and fusion processes display diurnal changes that are
      aligned to the light/darkness cycle. Besides morphological changes, mitochondrial
      respiration also displays diurnal changes. Disturbing the molecular clock in
      animal models leads to abrogated mitochondrial rhythmicity and altered
      respiration. Moreover, mitochondrial-dependent production of reactive oxygen
      species, which plays a role in cellular signaling, has also been linked to the
      circadian clock. In this review, we will summarize recent advances in the study
      of circadian rhythms of mitochondria and how this is linked to the molecular
      circadian clock.

PMID- 29378774
TI  - CD1d-mediated lipid presentation by CD11c+ cells regulates intestinal
      homeostasis.
AB  - Intestinal homeostasis relies on a continuous dialogue between the commensal
      bacteria and the immune system. Natural killer T (NKT) cells, which recognize
      CD1d-restricted microbial lipids and self-lipids, contribute to the regulation of
      mucosal immunity, yet the mechanisms underlying their functions remain poorly
      understood. Here, we demonstrate that NKT cells respond to intestinal lipids and
      CD11c+ cells (including dendritic cells (DCs) and macrophages) are essential to
      mediate lipid presentation within the gut ultimately controlling intestinal NKT
      cell homeostasis and activation. Conversely, CD1d and NKT cells participate in
      the control of the intestinal bacteria composition and compartmentalization, in
      the regulation of the IgA repertoire and in the induction of regulatory T cells
      within the gut. These changes in intestinal homeostasis require CD1d expression
      on DC/macrophage populations as mice with conditional deletion of CD1d on CD11c+
      cells exhibit dysbiosis and altered immune homeostasis. These results unveil the
      importance of CD11c+ cells in controlling lipid-dependent immunity in the
      intestinal compartment and reveal an NKT cell-DC crosstalk as a key mechanism for
      the regulation of gut homeostasis.

PMID- 29378777
TI  - Trends in Diabetes-Related Preventable Hospitalizations in the U.S., 2005-2014.

PMID- 29378776
TI  - Excess Mortality in Patients With Type 1 Diabetes Without Albuminuria-Separating
      the Contribution of Early and Late Risks.
AB  - OBJECTIVE: The current study investigated whether the risk of mortality in
      patients with type 1 diabetes without any signs of albuminuria is different than
      in the general population and matched control subjects without diabetes. RESEARCH
      DESIGN AND METHODS: We studied a nationwide, population-based Finnish register of
      10,737 patients diagnosed with type 1 diabetes during 1980-2005 and followed for
      10 years and 2,544 adults with long-standing diabetes drawn from the Finnish
      Diabetic Nephropathy Study (FinnDiane). Mortality was compared with the general
      Finnish population and 6,655 control subjects without diabetes. RESULTS: The
      standardized mortality ratio (SMR) was increased during the first 10 years after
      the diagnosis (2.58 [95% CI 2.07-3.18], P < 0.001). Mortality in adults with long
      standing diabetes, but without albuminuria, was no different from that of the
      general population (1.02 [0.84-1.22], P = 0.83). However, it was higher compared
      with that of control subjects without diabetes (1.33 [1.06-1.66], P = 0.01).
      Excess mortality was largely due to acute diabetes complications and ischemic
      heart disease, which remained more than fourfold higher (mortality rate ratio
      4.34 [2.49-7.57]) in adults with type 1 diabetes than in control subjects without
      diabetes, despite the absence of albuminuria. By contrast, deaths due to alcohol
      and drugs were reduced in adults with type 1 diabetes (P = 0.007), especially in
      men. CONCLUSIONS: Excess mortality in type 1 diabetes is the result of its
      complications. Acute complications drive an increased SMR in the first years. In
      individuals who remain free of albuminuria, mortality due to ischemic heart
      disease is still four times higher, and acute complications also occur.

PMID- 29378775
TI  - ERAD-dependent control of the Wnt secretory factor Evi.
AB  - Active regulation of protein abundance is an essential strategy to modulate
      cellular signaling pathways. Within the Wnt signaling cascade, regulated
      degradation of beta-catenin by the ubiquitin-proteasome system (UPS) affects the
      outcome of canonical Wnt signaling. Here, we found that abundance of the Wnt
      cargo receptor Evi (Wls/GPR177), which is required for Wnt protein secretion, is
      also regulated by the UPS through endoplasmic reticulum (ER)-associated
      degradation (ERAD). In the absence of Wnt ligands, Evi is ubiquitinated and
      targeted for ERAD in a VCP-dependent manner. Ubiquitination of Evi involves the
      E2-conjugating enzyme UBE2J2 and the E3-ligase CGRRF1. Furthermore, we show that
      a triaging complex of Porcn and VCP determines whether Evi enters the secretory
      or the ERAD pathway. In this way, ERAD-dependent control of Evi availability
      impacts the scale of Wnt protein secretion by adjusting the amount of Evi to meet
      the requirement of Wnt protein export. As Wnt and Evi protein levels are often
      dysregulated in cancer, targeting regulatory ERAD components might be a useful
      approach for therapeutic interventions.

PMID- 29378778
TI  - Deficiency in T follicular regulatory cells promotes autoimmunity.
AB  - T follicular regulatory (Tfr) cells are a new subset of regulatory T (T reg)
      cells localized in the germinal center to limit the humoral response. Until now,
      the physiological function of Tfr cells has been largely unknown. In this study,
      we developed a Bcl6fl/flFoxp3Cre mouse to analyze the function of Tfr cells in
      immune and autoimmune responses. These mice exhibited enhanced immunity to
      influenza virus; moreover, Bcl6fl/flFoxp3Cre/Cre mice developed late-onset
      spontaneous autoimmune diseases, affecting the salivary glands with lymphocyte
      infiltration and antibody deposition. In a mouse experimental Sjogren's syndrome
      model, ablation of Bcl6 in T reg cells greatly enhanced disease development.
      Conversely, Bcl6fl/flCd4Cre mice were protected in the model. Thus, our study
      indicates that Tfr cells control autoimmune diseases and can be targeted in
      infectious and autoimmune disease.

PMID- 29378779
TI  - Geographic epidemiology of medullary thyroid cancer families: unearthing European
      ancestral heritage.

PMID- 29378780
TI  - Visualizing transcription factor dynamics in living cells.
AB  - The assembly of sequence-specific enhancer-binding transcription factors (TFs) at
      cis-regulatory elements in the genome has long been regarded as the fundamental
      mechanism driving cell type-specific gene expression. However, despite extensive
      biochemical, genetic, and genomic studies in the past three decades, our
      understanding of molecular mechanisms underlying enhancer-mediated gene
      regulation remains incomplete. Recent advances in imaging technologies now enable
      direct visualization of TF-driven regulatory events and transcriptional
      activities at the single-cell, single-molecule level. The ability to observe the
      remarkably dynamic behavior of individual TFs in live cells at high
      spatiotemporal resolution has begun to provide novel mechanistic insights and
      promises new advances in deciphering causal-functional relationships of TF
      targeting, genome organization, and gene activation. In this review, we review
      current transcription imaging techniques and summarize converging results from
      various lines of research that may instigate a revision of models to describe key
      features of eukaryotic gene regulation.

PMID- 29378783
TI  - Correction: Mind the (sr)GAP - roles of Slit-Robo GAPs in neurons, brains and
      beyond (doi: 10.1242/jcs.207456).

PMID- 29378781
TI  - The role of lipoprotein (a) in chronic kidney disease.
AB  - Lipoprotein (a) [Lp(a)] and its measurement, structure and function, the impact
      of ethnicity and environmental factors, epidemiological and genetic associations
      with vascular disease, and new prospects in drug development have been
      extensively examined throughout this Thematic Review Series on Lp(a). Studies
      suggest that the kidney has a role in Lp(a) catabolism, and that Lp(a) levels are
      increased in association with kidney disease only for people with large apo(a)
      isoforms. By contrast, in those patients with large protein losses, as in the
      nephrotic syndrome and continuous ambulatory peritoneal dialysis, Lp(a) is
      increased irrespective of apo(a) isoform size. Such acquired abnormalities can be
      reversed by kidney transplantation or remission of nephrosis. In this Thematic
      Review, we focus on the relationship between Lp(a), chronic kidney disease, and
      risk of cardiovascular events.

PMID- 29378784
TI  - Dutch practice of euthanasia and assisted suicide: a glimpse at the edges of the
      practice.

PMID- 29378782
TI  - Inhibition of acid sphingomyelinase disrupts LYNUS signaling and triggers
      autophagy.
AB  - Activation of the lysosomal ceramide-producing enzyme, acid sphingomyelinase
      (ASM), by various stresses is centrally involved in cell death and has been
      implicated in autophagy. We set out to investigate the role of the baseline ASM
      activity in maintaining physiological functions of lysosomes, focusing on the
      lysosomal nutrient-sensing complex (LYNUS), a lysosomal membrane-anchored
      multiprotein complex that includes mammalian target of rapamycin (mTOR) and
      transcription factor EB (TFEB). ASM inhibition with imipramine or sphingomyelin
      phosphodiesterase 1 (SMPD1) siRNA in human lung cells, or by transgenic Smpd1+/-
      haploinsufficiency of mouse lungs, markedly reduced mTOR- and P70-S6 kinase (Thr
      389)-phosphorylation and modified TFEB in a pattern consistent with its
      activation. Inhibition of baseline ASM activity significantly increased autophagy
      with preserved degradative potential. Pulse labeling of sphingolipid metabolites
      revealed that ASM inhibition markedly decreased sphingosine (Sph) and Sph-1
      phosphate (S1P) levels at the level of ceramide hydrolysis. These findings
      suggest that ASM functions to maintain physiological mTOR signaling and inhibit
      autophagy and implicate Sph and/or S1P in the control of lysosomal function.

PMID- 29378785
TI  - The Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC)
      Study: Description and Baseline Characteristics of Participants.
AB  - Background: The Women's Health Initiative (WHI) Life and Longevity After Cancer
      (LILAC) study offers an important opportunity to advance cancer research by
      extending the original WHI studies to examine survivorship in women diagnosed
      with cancer during their participation in WHI.Methods: The goals of LILAC are to
      (i) obtain cancer treatment information and long-term cancer outcomes for women
      diagnosed with one of eight selected cancers (breast, endometrial, ovarian, lung,
      and colorectal cancers, and melanoma, lymphoma, and leukemia); (ii) augment the
      existing WHI biorepository with fixed tumor tissue from the solid tumor sites for
      cancers diagnosed since 2002; and (iii) develop, refine, and validate methods to
      use administrative data to capture treatment and recurrence data. Methods for
      accomplishing these goals are described, as are results from the initial LILAC
      participant survey.Results: A total of 9,934 WHI participants living with cancer
      were eligible for LILAC participation, of which 78% (N = 7,760) agreed to
      participate. Among the three most prevalent cancer types, 54% are breast cancer
      survivors, 11% are melanoma survivors, and 10% are survivors of colorectal
      cancer.Conclusions: In addition to describing this resource, we present pertinent
      lessons that may assist other investigators interested in embedding survivorship
      research into existing large epidemiologic cohorts.Impact: The LILAC resource
      offers a valuable opportunity for researchers to study cancer survivorship and
      issues pertinent to cancer survivors in future studies. Cancer Epidemiol
      Biomarkers Prev; 27(2); 125-37. (c)2017 AACR.

PMID- 29378786
TI  - What drives UK military personnel to seek mental healthcare, work strain or
      something else?
AB  - BACKGROUND: The numbers of UK military personnel referred to military departments
      of community mental health (DCMH) have increased annually over recent years; the
      reasons for such an increase are unclear. METHOD: Data for this study were
      derived from 549 DCMH attendees and 3682 serving regular military personnel. DCMH
      attendees completed a checklist of potential reasons for help-seeking. Cohort
      members provided data on perceived mental health problems and help-seeking from
      specialist mental health services. Both samples provided work strain and basic
      sociodemographic data. Work strain levels were compared among cohort and DCMH
      help seekers and non-help seekers using adjusted logistic regression analyses.
      RESULTS: Perceiving that mental health-related stigmatisation had reduced and
      being prompted to seek help by attending a health promotion event were among the
      least frequent reasons for seeking help in DCMH attendees. Realising that help
      was needed and being urged to seek help by one's partner, friends or family were
      the most common. Working very hard and experiencing excessive work were the most
      common work strain factors. Overall, the greatest levels of work strain were
      found among DCMH attendees. In all subsamples, work strain was significantly
      associated with experiencing a perceived mental health problem irrespective of
      whether help was sought or not. CONCLUSION: Work strain was significantly
      associated with experiencing a stressful, emotional, mental health or alcohol
      problem and was the highest among current DCMH help seekers. Recognising that
      help was required and being prompted by a significant other were the main drivers
      for help-seeking among DCMH attendees.

PMID- 29378787
TI  - Widespread transcriptional pausing and elongation control at enhancers.
AB  - Regulation by gene-distal enhancers is critical for cell type-specific and
      condition-specific patterns of gene expression. Thus, to understand the basis of
      gene activity in a given cell type or tissue, we must identify the precise
      locations of enhancers and functionally characterize their behaviors. Here, we
      demonstrate that transcription is a nearly universal feature of enhancers in
      Drosophila and mammalian cells and that nascent RNA sequencing strategies are
      optimal for identification of both enhancers and superenhancers. We dissect the
      mechanisms governing enhancer transcription and discover remarkable similarities
      to transcription at protein-coding genes. We show that RNA polymerase II (RNAPII)
      undergoes regulated pausing and release at enhancers. However, as compared with
      mRNA genes, RNAPII at enhancers is less stable and more prone to early
      termination. Furthermore, we found that the level of histone H3 Lys4 (H3K4)
      methylation at enhancers corresponds to transcriptional activity such that highly
      active enhancers display H3K4 trimethylation rather than the H3K4 monomethylation
      considered a hallmark of enhancers. Finally, our work provides insights into the
      unique characteristics of superenhancers, which stimulate high-level gene
      expression through rapid pause release; interestingly, this property renders
      associated genes resistant to the loss of factors that stabilize paused RNAPII.

PMID- 29378788
TI  - The degree of enhancer or promoter activity is reflected by the levels and
      directionality of eRNA transcription.
AB  - Gene expression is regulated by promoters, which initiate transcription, and
      enhancers, which control their temporal and spatial activity. However, the
      discovery that mammalian enhancers also initiate transcription questions the
      inherent differences between enhancers and promoters. Here, we investigate the
      transcriptional properties of enhancers during Drosophila embryogenesis using
      characterized developmental enhancers. We show that while the timing of enhancer
      transcription is generally correlated with enhancer activity, the levels and
      directionality of transcription are highly varied among active enhancers. To
      assess how this impacts function, we developed a dual transgenic assay to
      simultaneously measure enhancer and promoter activities from a single element in
      the same embryo. Extensive transgenic analysis revealed a relationship between
      the direction of endogenous transcription and the ability to function as an
      enhancer or promoter in vivo, although enhancer RNA (eRNA) production and
      activity are not always strictly coupled. Some enhancers (mainly bidirectional)
      can act as weak promoters, producing overlapping spatio-temporal expression.
      Conversely, bidirectional promoters often act as strong enhancers, while
      unidirectional promoters generally cannot. The balance between enhancer and
      promoter activity is generally reflected in the levels and directionality of eRNA
      transcription and is likely an inherent sequence property of the elements
      themselves.

PMID- 29378789
TI  - Teenage exercise is associated with earlier symptom onset in dysferlinopathy: a
      retrospective cohort study.

PMID- 29378790
TI  - Features of GBA-associated Parkinson's disease at presentation in the UK Tracking
      Parkinson's study.
AB  - OBJECTIVES: To examine the influence of the glucocerebrosidase (GBA) mutation
      carrier state on age at onset of Parkinson's disease (PD), the motor phenotype
      and cognitive function at baseline assessment in a large cohort of UK patients.
      We also analysed the prevalence of mood and behavioural problems that may
      confound the assessment of cognitive function. METHODS: We prospectively
      recruited patients with PD in the Tracking Parkinson's study. We fully sequenced
      the GBA gene in all recently diagnosed patients (<=3.5 years). We examined
      cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society
      Unified Parkinson's Disease Rating Scale part 3) function at a baseline
      assessment, at an average of 1.3 years after diagnosis. We used logistic
      regression to determine predictors of PD with mild cognitive impairment and PD
      with dementia. RESULTS: We studied 1893 patients with PD: 48 (2.5%) were
      heterozygous carriers for known Gaucher's disease (GD) causing pathogenic
      mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD,
      and 28 (1.5%) patients carried variants of unknown significance in the GBA gene.
      L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA
      mutations were on average 5 years younger at disease onset compared with non
      carriers (P=0.02). PD patients with GD-causing mutations did not have an
      increased family risk of PD. Patients with GBA mutations were more likely to
      present with the postural instability gait difficulty phenotype compared with non
      carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more
      advanced Hoehn and Yahr stage after adjustment for age and disease duration
      compared with non-carriers (P=0.005). There were no differences in cognitive
      function between GBA mutation carriers and non-carriers at this early disease
      stage. CONCLUSIONS: Our study confirms the influence of GBA mutations on the age
      of onset, disease severity and motor phenotype in patients with PD. Cognition did
      not differ between GBA mutation carriers and non-carriers at baseline, implying
      that cognitive impairment/dementia, reported in other studies at a later disease
      stage, is not present in recently diagnosed cases. This offers an important
      window of opportunity for potential disease-modifying therapy that may protect
      against the development of dementia in GBA-PD. CLINICAL TRIAL REGISTRATION:
      NCT02881099; Results.

PMID- 29378791
TI  - Pneumococcal Phenotype and Interaction with Nontypeable Haemophilus influenzae as
      Determinants of Otitis Media Progression.
AB  - All-cause otitis media (OM) incidence has declined in numerous settings following
      introduction of pneumococcal conjugate vaccines (PCVs) despite increases in
      carriage of nonvaccine pneumococcal serotypes escaping immune pressure. To
      understand the basis for the declining incidence, we assessed the intrinsic
      capacity of pneumococcal serotypes to cause OM independently and in polymicrobial
      infections involving nontypeable Haemophilus influenzae (NTHi) using samples
      obtained from middle ear fluid and nasopharyngeal cultures before PCV7/13
      rollout. Data included samples from OM episodes (11,811) submitted for cultures
      during a 10-year prospective study in southern Israel and nasopharyngeal samples
      (1,588) from unvaccinated asymptomatic children in the same population. We
      compared data representing pneumococcal serotype diversity across carriage and
      disease isolates with and without NTHi coisolation. We also measured associations
      between the pneumococcal phenotype and the rate of progression from colonization
      to OM in the presence and absence of NTHi. Whereas pneumococcal serotype
      diversity was lower in single-species OM than in single-species colonization,
      levels of serotype diversity did not differ significantly between colonization
      and OM in mixed-species episodes. Serotypes differed roughly 100-fold in
      progression rates, and those differences were attenuated in polymicrobial
      episodes. Vaccine serotype pneumococci had higher rates of progression than
      nonvaccine serotypes. While serotype invasiveness was a weak predictor of the OM
      progression rate, efficient capsular metabolic properties-traditionally thought
      to serve as an advantage in colonization-predicted an enhanced rate of
      progression to complex OM. The lower capacity of nonvaccine serotypes to cause OM
      may partially account for reductions in all-cause OM incidence despite serotype
      replacement in carriage following rollout of PCVs.

PMID- 29378792
TI  - Brucella abortus senses the intracellular environment through the two-component
      system BvrR/BvrS allowing the adaptation to its replicative niche.
AB  - Brucella abortus is a facultative extracellular-intracellular pathogen belonging
      a group of alpha-Proteobacteria that establishes close interactions with animal
      cells. This bacterium enters host cells in a membrane bound compartment, avoiding
      the lysosomal route and reaching the endoplasmic reticulum through the action of
      the Type IV secretion system, VirB. In this work we demonstrate that the two
      component system BvrR/BvrS senses the intracellular environment to mount the
      transcriptional response required for intracellular life adaptation. By combining
      a method to purify intracellularly extracted bacteria with a strategy that allows
      direct determination of BvrR phosphorylation we showed that upon entrance to host
      cells, the regulatory protein BvrR was activated (BvrR-P) by phosphorylation at
      aspartate 58. This activation takes place in response to intracellular cues found
      in early compartments, such as low pH and nutrient deprivation. Furthermore, BvrR
      activation was followed by an increase in the expression of VjbR and VirB. The in
      vitro activation of this BvrR-P/VjbR/VirB virulence circuit rescued B. abortus
      from the inhibition of intracellular replication induced by bafilomycin treatment
      of cells, demonstrating the relevance of this mechanism for the intracellular
      bacterial survival and replication. Altogether, our results indicate that B.
      abortus senses the transition from the extracellular to the intracellular milieu
      through BvrR/BvrS allowing the bacterium to transit safely to its replicative
      niche. These results serve as a working model for understanding the role of this
      family of two-component systems in the adaptation to intracellular life of alpha
      Proteobacteria.

PMID- 29378793
TI  - Role of the inducible adhesin, CpAls7, in binding of Candida parapsilosis to
      extracellular matrix under fluid shear.
AB  - The yeast, Candida parapsilosis, is an increasingly common cause of systemic
      fungal infections among the immune compromised, including premature infants.
      Adhesion to host surfaces is an important step in pathogenesis, but this process
      has not been extensively studied in this organism. A microfluidics assay was
      developed to test the ability of C. parapsilosis to adhere to immobilized host
      extracellular matrix proteins under physiologic fluid shear conditions. Growth in
      mammalian tissue culture media at 37 degrees C for 3-6 hours led to induction of
      an adhesive phenotype at shear forces of 1-5 dynes/cm2 in some isolates of C.
      parapsilosis Glutamic acid, proline and calcium appeared to be the minimally
      necessary requirements for increased adhesion in these assays. To determine
      whether genes homologous to the ALS gene family of C. albicans were important for
      the adhesive phenotype, expression of 5 homologous C. parapsilosis genes were
      quantified using qPCR under conditions leading to increased adhesion.
      CPAR2_404800 (CpALS7) and CPAR2_404780 showed increased expression compared to
      control yeast. The extent of adhesion was variable among different isolates, and
      linear regression identified expression of CpALS7 but not CPAR2_404780 to have a
      strong positive correlation with adhesion. A homozygous CpALS7 deletion strain
      was deficient in adhesion, whereas expression of CpALS7 in S. cerevisiae resulted
      in increased adhesion. Together, these data provide strong evidence that CpAls7
      aids in the adherence of C. parapsilosis to extracellular matrix under shear
      forces and support its previously reported role in virulence.

PMID- 29378794
TI  - Purification of Intracellular Bacterial Communities during Experimental Urinary
      Tract Infection Reveals an Abundant and Viable Bacterial Reservoir.
AB  - Urinary tract infections (UTIs) are a major infection of humans, particularly
      affecting women. Recurrent UTIs can cause significant discomfort and expose
      patients to high levels of antibiotic use, which in turn contributes to the
      development of higher antibiotic resistance rates. Most UTIs are caused by
      uropathogenic Escherichia coli, which is able to form intracellular collections
      (termed intracellular bacterial communities [IBCs]) within the epithelial cells
      lining the bladder lumen. IBCs are seen in both infected mice and humans and are
      a potential cause of recurrent UTI. Genetic and molecular studies of IBCs have
      been hampered both by the low number of bacteria in IBCs relative to the number
      extracellular bacteria and by population bottlenecks that occur during IBC
      formation. We now report the development of a simple and rapid technique for
      isolating pure IBCs from experimentally infected mice. We verified the
      specificity and purity of the isolated IBCs via microscopy, gene expression, and
      culture-based methods. Our results further demonstrated that our isolation
      technique practically enables specific molecular studies of IBCs. In the first
      such direct measurement, we determined that a single epithelial cell containing
      an early IBC typically contains 103 viable bacteria. Our isolation technique
      complements recent progress in low-input, single-cell genomics to enable future
      genomic studies of the formation of IBCs and their activation pathways during
      recurrent UTI, which may lead to novel strategies to eliminate them from the
      bladder.

PMID- 29378795
TI  - Small GTPase Immunity-Associated Proteins Mediate Resistance to Toxoplasma gondii
      Infection in Lewis Rat.
AB  - Rats vary in their susceptibilities to Toxoplasma gondii infection depending on
      the rat strain. Compared to the T. gondii-susceptible Brown Norway (BN) rat, the
      Lewis (LEW) rat is extremely resistant to T. gondii Thus, these two rat strains
      are ideal models for elucidating host mechanisms that are important for host
      resistance to T. gondii infection. Therefore, in our efforts to unravel molecular
      factors directing the protective early innate immune response in the LEW rat, we
      performed RNA sequencing analysis of the LEW versus BN rat with or without T.
      gondii infection. We identified three candidate small GTPase immunity-associated
      proteins (GIMAPs) that were upregulated (false discovery rate, 0.05) in the LEW
      rat in response to T. gondii infection. Subsequently, we engineered T. gondii
      susceptible NR8383 rat macrophage cells for overexpression of LEW rat-derived
      candidate GIMAP 4, 5, and 6. By immunofluorescence analysis we observed that
      GIMAP 4, 5, and 6 in T. gondii-infected NR8383 cells each colocalized with GRA5,
      a parasite parasitophorous vacuole membrane (PVM) marker protein, suggesting
      their translocation to the PVM. Interestingly, overexpression of each candidate
      GIMAP in T. gondii-infected NR8383 cells induced translocation of LAMP1, a
      lysosome marker protein, to the T. gondii surface membrane. Importantly,
      overexpression of GIMAP 4, 5, or 6 individually inhibited intracellular T. gondii
      growth, with GIMAP 4 having the highest inhibitory effect. Together, our findings
      indicate that upregulation of GIMAP 4, 5, and 6 contributes to the robust
      refractoriness of the LEW rat to T. gondii through induction of lysosomal fusion
      to the otherwise nonfusogenic PVM.

PMID- 29378796
TI  - Bacterial Periplasmic Oxidoreductases Control the Activity of Oxidized Human
      Antimicrobial beta-Defensin 1.
AB  - The antimicrobial peptide human beta-defensin 1 (hBD1) is continuously produced
      by epithelial cells in many tissues. Compared to other defensins, hBD1 has only
      minor antibiotic activity in its native state. After reduction of its disulfide
      bridges, however, it becomes a potent antimicrobial agent against bacteria, while
      the oxidized native form (hBD1ox) shows specific activity against Gram-negative
      bacteria. We show that the killing mechanism of hBD1ox depends on aerobic growth
      conditions and bacterial enzymes. We analyzed the different activities of hBD1
      using mutants of Escherichia coli lacking one or more specific proteins of their
      outer membrane, cytosol, or redox systems. We discovered that DsbA and DsbB are
      essential for the antimicrobial activity of hBD1ox but not for that of reduced
      hBD1 (hBD1red). Furthermore, our results strongly suggest that hBD1ox uses outer
      membrane protein FepA to penetrate the bacterial periplasm space. In contrast,
      other bacterial proteins in the outer membrane and cytosol did not modify the
      antimicrobial activity. Using immunogold labeling, we identified the localization
      of hBD1ox in the periplasmic space and partly in the outer membrane of E. coli
      However, in resistant mutants lacking DsbA and DsbB, hBD1ox was detected mainly
      in the bacterial cytosol. In summary, we discovered that hBD1ox could use FepA to
      enter the periplasmic space, where its activity depends on presence of DsbA and
      DsbB. HBD1ox concentrates in the periplasm in Gram-negative bacteria, which
      finally leads to bleb formation and death of the bacteria. Thus, the bacterial
      redox system plays an essential role in mechanisms of resistance against host
      derived peptides such as hBD1.

PMID- 29378797
TI  - Clinical Outcomes of Submicroscopic Infections and Correlates of Protection of
      VAR2CSA Antibodies in a Longitudinal Study of Pregnant Women in Colombia.
AB  - Malaria in pregnancy can cause serious adverse outcomes for the mother and the
      fetus. However, little is known about the effects of submicroscopic infections
      (SMIs) in pregnancy, particularly in areas where Plasmodium falciparum and
      Plasmodium vivax cocirculate. A cohort of 187 pregnant women living in Puerto
      Libertador in northwest Colombia was followed longitudinally from recruitment to
      delivery. Malaria was diagnosed by microscopy, reverse transcription-quantitative
      PCR (RT-qPCR), and placental histopathology. Gestational age, hemoglobin
      concentration, VAR2CSA-specific IgG levels, and adhesion-blocking antibodies were
      measured during pregnancy. Statistical analyses were performed to evaluate the
      impact of SMIs on birth weight and other delivery outcomes. Twenty-five percent
      of women (45/180) were positive for SMIs during pregnancy. Forty-seven percent of
      infections (21/45) were caused by P. falciparum, 33% were caused by P. vivax, and
      20% were caused by mixed Plasmodium spp. Mixed infections of P. falciparum and P.
      vivax were associated with lower gestational age at delivery (P = 0.0033), while
      other outcomes were normal. Over 60% of women had antibodies to VAR2CSA, and
      there was no difference in antibody levels between those with and without SMIs.
      The anti-adhesion function of these antibodies was associated with protection
      from SMI-related anemia at delivery (P = 0.0086). SMIs occur frequently during
      pregnancy, and while mixed infections of both P. falciparum and P. vivax were not
      associated with a decrease in birth weight, they were associated with significant
      risk of preterm birth. We propose that the lack of adverse delivery outcomes is
      due to functional VAR2CSA antibodies that can protect pregnant women from SMI
      related anemia.

PMID- 29378800
TI  - Growth, Change...and Gratitude!

PMID- 29378798
TI  - Streptococcus pneumoniae PspC Subgroup Prevalence in Invasive Disease and
      Differences in Contribution to Complement Evasion.
AB  - The pneumococcal capsular serotype is an important determinant of complement
      resistance and invasive disease potential, but other virulence factors have also
      been found to contribute. Pneumococcal surface protein C (PspC), a highly
      variable virulence protein that binds complement factor H to evade C3
      opsonization, is divided into two subgroups: choline-bound subgroup I and LPxTG
      anchored subgroup II. The prevalence of different PspC subgroups in invasive
      pneumococcal disease (IPD) and functional differences in complement evasion are
      unknown. The prevalence of PspC subgroups in IPD isolates was determined in a
      collection of 349 sequenced strains of Streptococcus pneumoniae isolated from
      adult patients. pspC deletion mutants and isogenic pspC switch mutants were
      constructed to study differences in factor H binding and complement evasion in
      relation to capsule thickness. Subgroup I pspC was far more prevalent in IPD
      isolates than subgroup II pspC The presence of capsule was associated with a
      greater ability of bound factor H to reduce complement opsonization. Pneumococcal
      subgroup I PspC bound significantly more factor H and showed more effective
      complement evasion than subgroup II PspC in isogenic encapsulated pneumococci. We
      conclude that variation in the PspC subgroups, independent of capsule serotypes,
      affects pneumococcal factor H binding and its ability to evade complement
      deposition.

PMID- 29378799
TI  - A Vaginal Tract Signal Detected by the Group B Streptococcus SaeRS System Elicits
      Transcriptomic Changes and Enhances Murine Colonization.
AB  - Streptococcus agalactiae (group B streptococcus [GBS]) can colonize the human
      vaginal tract, leading to both superficial and serious infections in adults and
      neonates. To study bacterial colonization of the reproductive tract in a
      mammalian system, we employed a murine vaginal carriage model. Using
      transcriptome sequencing (RNA-Seq), the transcriptome of GBS growing in vivo
      during vaginal carriage was determined. Over one-quarter of the genes in GBS were
      found to be differentially regulated during in vivo colonization compared to
      laboratory cultures. A two-component system (TCS) homologous to the
      staphylococcal virulence regulator SaeRS was identified as being upregulated in
      vivo One of the SaeRS targets, pbsP, a proposed GBS vaccine candidate, is shown
      to be important for colonization of the vaginal tract. A component of vaginal
      lavage fluid acts as a signal to turn on pbsP expression via SaeRS. These data
      demonstrate the ability to quantify RNA expression directly from the murine
      vaginal tract and identify novel genes involved in vaginal colonization by GBS.
      They also provide more information about the regulation of an important virulence
      and colonization factor of GBS, pbsP, by the TCS SaeRS.

PMID- 29378801
TI  - Impact of Operator Positioning on Musculoskeletal Disorders and Work Habits Among
      Mississippi Dental Hygienists.
AB  - Purpose: The purpose of this study was to assess impact of operator positioning
      on the development of musculoskeletal disorders (MSDs) and workforce issues among
      practicing dental hygienists in the state of Mississippi.Methods: The sample
      consisted of all dental hygienists (n=1,553) licensed in the state of
      Mississippi. A modified 47 item, online version of the Standardized Nordic
      Questionnaire was used to document the following: types of MSDs, practice
      history, operator positioning, ergonomic work habits and the impact of MSDs on
      workforce issues. Descriptive statistics were used to analyze practice history
      and work habits. Chi-square analysis examined the relationship between operator
      positioning and MSDs as well as the relationship between the onset of MSDs and
      their impact on patient workload, work hours, time off from work, and ability to
      practice clinical dental hygiene. Survival analyses were used to test the onset
      of MSDs in relationship to operator positioning.Results: The survey yielded a 22%
      (n=338) response rate. There was no significant difference in the prevalence of
      MSDs between those sitting in front of the patient as compared to those sitting
      behind the patient (PL) (chi2 (1) = 1.67, p=0.196), although respondents sitting
      behind the patient reported developing their MSDs earlier (chi2 (1) = 3.92,
      p=0.048). Of the participants who had practiced 15 or more years, 85% reported
      developing MSDs. However, only 13% reported ever having to modify their patient
      load. Sixteen percent reported reducing work hours and 21% reported taking time
      off from work due to MSDs.Conclusions: Regardless of the operator position used,
      the majority of practicing dental hygienists surveyed developed MSDs earlier than
      has been previously reported in the literature. Workforce related issues were not
      shown to have a negative impact on this study population.

PMID- 29378802
TI  - Assessing the Use of Loupes and Lights in Dental Hygiene Educational Programs.
AB  - Purpose: The purpose of this study was to explore the use of loupes and lights in
      dental hygiene programs, to assess why they are being used, and to evaluate at
      what point in time they are introduced to students within the curriculum.Methods:
      A 20 question survey was developed and pilot tested. The survey was disseminated
      electronically to 335 dental hygiene program directors in the United States.
      Frequency distributions were analyzed to provide an overview of the data and
      Fisher's Exact Test was used to investigate differences between
      technical/community college programs and university-based programs.Results: Out
      of the 335 electronic surveys, 143 were completed for a response rate of 47%.
      Prevention of musculoskeletal disorders, ergonomics, and enhanced vision for
      instrumentation remain the top three advantages of using loupes. Ninety-six
      percent of respondents indicated students use loupes and over 50% of faculty use
      loupes. Fifty-seven percent of dental hygiene programs encourage students to
      purchase loupes with a light. Fifty percent of students pay $601-$900 for loupes
      and 47% pay $300-$600 for a light.Conclusion: Student and faculty use of loupes
      and lights are increasing in educational programs. Future research should focus
      on the longitudinal impact of using loupes/lights, the prevention of
      musculoskeletal disorders, and an investigation of the continued use of loupes in
      a professional setting post-graduation.

PMID- 29378803
TI  - Oral Manifestations of Menopause: An Interprofessional Intervention for Dental
      Hygiene and Physician Assistant Students.
AB  - Purpose: Interprofessional education (IPE) is a means of fostering integration
      and collaboration between health care professions. The purpose of this study was
      to evaluate the effect of an IPE educational module on dental hygiene (DH) and
      physician assistants (PA) students' knowledge of the oral manifestations of
      menopause and overall confidence in treating these conditions.Methods: A
      convenience sample of DH and PA students was used for this mixed-method study.
      Quantitative data was collected with pre- and post-tests using a modified
      Readiness for Interprofessional Learning Survey (RIPLS) and a principle
      investigator (PI)-designed knowledge of menopause test, to determine the
      students' attitudes and learning levels. Students participated in a one-time
      workshop that included an educational presentation on the oral manifestations of
      menopause and a case study exercise using a pseudo-standardized patient. Students
      from both disciplines, worked in preselected groups to create a patient care plan
      addressing the oral manifestations of menopause. Qualitative data was collected
      from student comments.Results: Study results indicate an increase in
      participants' knowledge of the oral manifestations of menopause (p<0.05). Results
      also suggest improved attitudes toward interprofessional teamwork and
      collaboration (p<0.05), positive professional identity (p<0.05), roles and
      responsibilities (p<0.05) for IPEC core competencies RR1, RR2, RR3, RR4,
      interprofessional communication (p<0.05) for IPEC core competencies CC3, CC4, CC
      6. Qualitative data from interprofessional care plan formulation and debriefing
      demonstrated facilitation of gained confidence in applying new skills related to
      the oral manifestations of menopause.Conclusion: Patients experiencing menopause
      are susceptible to oral manifestations. Implementation of an IPE intervention
      demonstrated correlation between an IPE experience and participants' knowledge,
      attitudes and confidence. Preparing students to meet the needs of menopausal
      women may ultimately decrease oral discomfort and improve overall quality of
      life.

PMID- 29378804
TI  - Hookah Smoking: Assessing College Students' Behaviors, Attitudes, and Knowledge.
AB  - Purpose: The objective of this study was to assess college students' behaviors,
      attitudes, and knowledge regarding hookah smoking.Methods: A convenience sample
      of 200 students from various majors, including allied health and nursing
      students, was used to conduct this study at a university located in the
      Midwestern United States. Respondents were asked about any past, current, and
      future hookah smoking behaviors. Likert-scale questions were used to assess
      attitudes regarding hookah smoking. Respondents were also asked ten questions
      regarding the history of and health effects of hookah smoking. A knowledge score
      was calculated based on the number of questions answered correctly. Survey data
      were analyzed using independent sample t-tests and a one-way ANOVA test at a
      significance level of p<0.05.Results: A total of 200 out of 204 surveys were
      returned, yielding an overall response rate of 98%. Sixty-eight percent of
      respondents reported having participated in hookah smoking, with time of first
      time use ranging from 14 to 21 years of age. About one third of the respondents
      (32%) reported participating in hookah smoking in the previous 30 days. The
      majority (68%)of respondents estimated that they would not participate in hookah
      smoking in five years time. Over half of the respondents reported that it is
      socially acceptable to participate in hookah smoking and 43% reported that hookah
      smoking has relaxation benefits. The overall mean knowledge score regarding the
      health effects of hookah usage was 4.4 questions correct out of 10. There was a
      significant difference (p=.038) in the mean knowledge scores between hookah users
      (4.70) and non-users (3.81). When comparing the knowledge of allied health and
      nursing majors to all other majors, the allied health and nursing group scored
      significantly higher (p=.017) than the non-allied health and nursing majors, with
      mean scores of 4.80 and 3.81, respectively. Thirty-nine percent of the
      respondents were unaware that hookah tobacco and related smoke can cause oral
      cancer.Conclusion: Based on the high rates of college student use and the low
      knowledge scores, this study supports need for more education about hookah
      smoking and its health consequences.

PMID- 29378805
TI  - Patients' Willingness to Participate in Rapid HIV Testing: A pilot study in three
      New York City dental hygiene clinics.
AB  - Purpose: One in eight people living with an HIV infection in the United States is
      unaware of their status. Rapid HIV testing (RHT) is an easily used and accepted
      screening tool that has been introduced in a limited number of clinical settings.
      The purpose of this study was to investigate patient acceptability, certainty of
      their decision, and willingness to pay for screening if RHT was offered in
      university-based dental hygiene clinics.Methods: A cross-sectional survey was
      administered to 426 patients at three dental hygiene clinics in New York City
      over a period of four months. The survey questionnaire was based on the
      decisional conflict scale measuring personal perceptions; with zero indicating
      extremely high conflict to four indicating no conflict. Patients were assessed
      for their acceptance of RHT, provider preference for administration of the test
      and their willingness to pay for RHT.Results: Over half (72.2%) indicated
      acceptance of HIV testing in a dental hygiene clinic setting; with 85.3% choosing
      oral RHT, 4.9% fingerstick RHT, and 8.8% venipuncture. Respondents were amenable
      to testing when offered by dental hygienists (71.7%) and dentists (72.4%). Over
      30% indicated their willingness to receive HIV testing in the dental setting when
      offered at no additional cost. The mean decisional conflict score was 3.42/4.0
      indicating no decisional conflict.Conclusions: Patients are willing to undergo
      oral RHT when offered as a service and provided by dental hygienists in the
      dental setting. Patients appear to be aware of the benefits and risks associated
      with RHT. Further research is needed to evaluate the public health benefits and
      logistical challenges facing the delivery of RHT within in the dental setting.

PMID- 29378806
TI  - The Value of Interprofessional Education: Assessing the Attitudes of Dental
      Hygiene Administrators and Faculty.
AB  - Purpose: The purpose of this study was to assess the attitudes of dental hygiene
      administrators and faculty members about the value of interprofessional education
      (IPE) within dental hygiene curricula and to determine whether administrator and
      faculty perspectives were associated with their professional role, gender,
      experience, knowledge about IPE, and their use of collaborative teaching
      strategies.Methods: A 34-question survey was used to evaluate dental hygiene
      administrators' and faculty knowledge, attitudes, and practices related to IPE.
      Electronic surveys were distributed to 224 program directors and faculty members
      of all entry-level dental hygiene programs located within the Northeast region of
      the United States. Responses were tabulated and analyzed using Statistical
      Package for the Social Sciences 23. Descriptive statistics, the Spearman's rho
      correlation coefficient, and ordinal regression analyses were used to report on
      each survey item.Results: The response rate was 41% (n=91). Overall, respondents
      viewed interprofessional pedagogy in high regard. Administrators and faculty
      agreed that IPE would enhance views towards other professions, benefit patients,
      and assist students in becoming effective members of health care teams. Although
      the basis for these perspectives was distributed, most (36%) were attributed to
      being in favor of working with other professionals. Significant correlations were
      found between respondent attitudes and their understanding and use of
      collaborative education strategies. Knowledge levels ranged from limited (38%) to
      adequate (58%). Approximately half of respondents (48%) reported that they are in
      the very initial stages of incorporating IPE into the curriculum.Conclusion: The
      majority of the dental hygiene administrators and faculty members surveyed see
      the value and significance of using IPE to effectively prepare students to enter
      a collaborative workforce. These perspectives demonstrate that dental hygiene is
      on the appropriate path for incorporating interprofessional strategies into
      program curricula.

PMID- 29378807
TI  - Compensation and Position Characteristics of Dental Hygiene Program Directors.
AB  - Purpose: The purpose of this study was to collect information about dental
      hygiene program directors (PD) in order to create a comprehensive position
      profile for the profession and add to the current literature regarding employment
      trends and compensation in dental hygiene education. Information gained through
      this study addresses a gap in the literature and could be utilized by current and
      future educators considering a dental hygiene program director role or for
      recruitment purposes.Methods: An electronic survey, consisting of 38 items
      addressing areas including job characteristics, requirements, compensation, and
      anticipated retirement, was sent to PDs of all the Commission on Dental
      Accreditation (CODA) accredited dental hygiene programs in the United States
      (n=314). Descriptive and inferential statistics were used to analyze the data.
      ANOVA analyses were used to determine whether significant differences existed
      regarding salary and compensation, contact hours, total working hours, contract
      characteristics, and job expectations.Results: Directors from 122 programs
      responded yielding a response rate of 39%. Seventy-one percent of respondents
      were aged 50-59 years and 46% reported having held the program director position
      for 3 years or less. Thirty-five percent of participants plan to retire from
      their program director position in the next five years. In regards to
      compensation, 47% of respondents indicated making between $60,000 and $79,999 and
      3% reported earning less than $40,000 while 4% indicated salaries over $100,000.
      Total number of teaching years and highest degree held demonstrated a positive
      impact on adjusted monthly salary. PDs employed in university settings were
      significantly more likely to have ongoing requirements for scholarly activity;
      those employed in settings associated with a dental school had a longer average
      contract length than directors in other institutions. Potential dental hygiene
      PDs should expect an average workweek of 40-50 hours, with the majority of the
      time spent on administrative duties. Additional responsibilities include
      teaching, scholarly activity, and committee work.Conclusion: A position profile
      detailing the range of employment expectations for dental hygiene PDs has been
      created and can serve as a guide to inform and recruit potential program
      directors.

PMID- 29378809
TI  - Mosaic Analysis in Drosophila.
AB  - Since the founding of Drosophila genetics by Thomas Hunt Morgan and his
      colleagues over 100 years ago, the experimental induction of mosaicism has
      featured prominently in its recognition as an unsurpassed genetic model organism.
      The use of genetic mosaics has facilitated the discovery of a wide variety of
      developmental processes, identified specific cell lineages, allowed the study of
      recessive embryonic lethal mutations, and demonstrated the existence of cell
      competition. Here, we discuss how genetic mosaicism in Drosophila became an
      invaluable research tool that revolutionized developmental biology. We describe
      the prevailing methods used to produce mosaic animals, and highlight advantages
      and disadvantages of each genetic system. We cover methods ranging from simple
      "twin-spot" analysis to more sophisticated systems of multicolor labeling.

PMID- 29378812
TI  - Heartbeat: Transcatheter procedures for secondary mitral regurgitation?

PMID- 29378813
TI  - Does antibiotic prophylaxis really prevent streptococci infective endocarditis?

PMID- 29378810
TI  - Repressive Chromatin in Caenorhabditis elegans: Establishment, Composition, and
      Function.
AB  - Chromatin is organized and compacted in the nucleus through the association of
      histones and other proteins, which together control genomic activity. Two broad
      types of chromatin can be distinguished: euchromatin, which is generally
      transcriptionally active, and heterochromatin, which is repressed. Here we
      examine the current state of our understanding of repressed chromatin in
      Caenorhabditis elegans, focusing on roles of histone modifications associated
      with repression, such as methylation of histone H3 lysine 9 (H3K9me2/3) or the
      Polycomb Repressive Complex 2 (MES-2/3/6)-deposited modification H3K27me3, and on
      proteins that recognize these modifications. Proteins involved in chromatin
      repression are important for development, and have demonstrated roles in nuclear
      organization, repetitive element silencing, genome integrity, and the regulation
      of euchromatin. Additionally, chromatin factors participate in repression with
      small RNA pathways. Recent findings shed light on heterochromatin function and
      regulation in C. elegans, and should inform our understanding of repressed
      chromatin in other animals.

PMID- 29378815
TI  - Distinct physiological, biochemical and morphometric adjustments in the malaria
      vectors Anopheles gambiae and A. coluzzii as means to survive dry season
      conditions in Burkina Faso.
AB  - Aestivation and dispersive migration are the two strategies evoked in the
      literature to explain the way in which malaria vectors Anopheles coluzzii and A.
      gambiae survive the harsh climatic conditions of the dry season in sub-Saharan
      Africa. However, the physiological mechanisms regulating these two strategies are
      unknown. In the present study, mosquito species were exposed to controlled
      environmental conditions mimicking the rainy and dry seasons of south western
      Burkina Faso. Survival strategies were studied through morphometric (wing
      length), ecophysiological (respiratory gas exchanges), biochemical (cuticular
      hydrocarbons composition) and molecular (AKH mRNA expression levels) parameters,
      variations of which are usually considered to be hallmarks of aestivation and
      dispersion mechanisms in various insects. Our results showed that
      ecophysiological and morphometric adjustments are made in both species to prevent
      water losses during the dry season. However, the usual metabolic rate
      modifications expected as signatures of aestivation and migration were not
      observed, highlighting specific and original physiological mechanisms sustaining
      survival in malaria mosquitoes during the dry season. Differences in epicuticular
      hydrocarbon composition and AKH levels of expression were found between the
      permanent and temporary A. coluzzii populations, illustrating the great
      phenotypic plasticity of this mosquito species. Altogether, our work underlines
      the diverse and complex pattern of changes occurring in the two mosquito species
      and at the population level to cope with the dry season and highlights potential
      targets of future control tools.

PMID- 29378814
TI  - Modeling signaling-dependent pluripotency with Boolean logic to predict cell fate
      transitions.
AB  - Pluripotent stem cells (PSCs) exist in multiple stable states, each with specific
      cellular properties and molecular signatures. The mechanisms that maintain
      pluripotency, or that cause its destabilization to initiate development, are
      complex and incompletely understood. We have developed a model to predict
      stabilized PSC gene regulatory network (GRN) states in response to input signals.
      Our strategy used random asynchronous Boolean simulations (R-ABS) to simulate
      single-cell fate transitions and strongly connected components (SCCs) strategy to
      represent population heterogeneity. This framework was applied to a reverse
      engineered and curated core GRN for mouse embryonic stem cells (mESCs) and used
      to simulate cellular responses to combinations of five signaling pathways. Our
      simulations predicted experimentally verified cell population compositions and
      input signal combinations controlling specific cell fate transitions. Extending
      the model to PSC differentiation, we predicted a combination of signaling
      activators and inhibitors that efficiently and robustly generated a Cdx2+Oct4-
      cells from naive mESCs. Overall, this platform provides new strategies to
      simulate cell fate transitions and the heterogeneity that typically occurs during
      development and differentiation.

PMID- 29378816
TI  - Pheromones modulate responsiveness to a noxious stimulus in honey bees.
AB  - Pheromones are chemical substances released into the environment by an
      individual, which trigger stereotyped behaviors and/or physiological processes in
      individuals of the same species. Yet, a novel hypothesis has suggested that
      pheromones not only elicit innate responses but also contribute to behavioral
      plasticity by affecting the subjective evaluation of appetitive or aversive
      stimuli. To test this hypothesis, we exposed bees to three pheromonal components
      whose valence was either negative (i.e. associated with aversive events:
      isopentyl acetate and 2-heptanone) or positive (i.e. associated with appetitive
      events: geraniol). We then determined the effect of this exposure on the
      subjective evaluation of aversive stimuli by quantifying responsiveness to a
      series of increasing electric shock voltages before and after exposure. Two
      experiments were conducted varying the time lapse between shock series (15 min in
      experiment 1, and 24 h in experiment 2). In experiment 1, we observed a general
      decrease of shock responsiveness caused by fatigue, due to the short lapse of
      time between the two series of shocks. This decrease could only be counteracted
      by isopentyl acetate. The enhancing effect of isopentyl acetate on shock
      responsiveness was also found in experiment 2. Conversely, geraniol decreased
      aversive responsiveness in this experiment; 2-heptanone did not affect aversive
      responsiveness in any experiment. Overall, our results demonstrate that certain
      pheromones modulate the salience of aversive stimuli according to their valence.
      In this way, they would affect the motivation to engage in aversive responses,
      thus acting as modulators of behavioral plasticity.

PMID- 29378817
TI  - Reduced thermal tolerance during salinity acclimation in brook trout (Salvelinus
      fontinalis) can be rescued by prior treatment with cortisol.
AB  - The aims of this study were to assess whether thermal tolerance of brook trout
      (Salvelinus fontinalis) is affected during seawater (SW) acclimation and to
      investigate the role of cortisol in osmoregulation and thermal tolerance during
      SW acclimation. Freshwater (FW)-acclimated brook trout at 18 degrees C (Tacc)
      were exposed to SW for 16 days, whilst maintaining a FW control. Fish were
      examined for critical thermal maximum (CTmax) 0 (before), 2, 5 and 16 days after
      SW exposure, and sampled at Tacc and CTmax for analysis of plasma cortisol,
      glucose and Cl-, gill Na+/K+-ATPase (NKA) activity and heat shock protein 70
      (HSP70) abundance, and white muscle water content. At 2 days in SW, CTmax was
      significantly reduced (from 31 to 26 degrees C), and then recovered by 16 days.
      This transient decrease in thermal tolerance coincided with a transient increase
      in plasma Cl- and decrease in muscle moisture content. Salinity itself had no
      effect on gill HSP70 abundance compared with the large and immediate effects of
      high temperature exposure during CTmax testing. To examine the role of cortisol
      in osmoregulation, brook trout were administered a cortisol implant (5 and 25 MUg
      g-1 CORT) prior to SW exposure. Both CORT doses significantly increased their
      capacity to maintain plasma Cl- during SW acclimation. Treatment with the 25 MUg
      g-1 CORT dose was shown to significantly improve CTmax after 2 days in SW, and
      CTmax was associated with plasma Cl- and muscle moisture content. These findings
      indicate that brook trout are sensitive to temperature during SW acclimation and
      that thermal tolerance is associated with ion and water balance during SW
      acclimation.

PMID- 29378808
TI  - Protecting and Diversifying the Germline.
AB  - Gametogenesis represents the most dramatic cellular differentiation pathways in
      both female and male flies. At the genome level, meiosis ensures that diploid
      germ cells become haploid gametes. At the epigenome level, extensive changes are
      required to turn on and shut off gene expression in a precise spatiotemporally
      controlled manner. Research applying conventional molecular genetics and cell
      biology, in combination with rapidly advancing genomic tools have helped us to
      investigate (1) how germ cells maintain lineage specificity throughout their
      adult reproductive lifetime; (2) what molecular mechanisms ensure proper
      oogenesis and spermatogenesis, as well as protect genome integrity of the
      germline; (3) how signaling pathways contribute to germline-soma communication;
      and (4) if such communication is important. In this chapter, we highlight recent
      discoveries that have improved our understanding of these questions. On the other
      hand, restarting a new life cycle upon fertilization is a unique challenge faced
      by gametes, raising questions that involve intergenerational and
      transgenerational epigenetic inheritance. Therefore, we also discuss new
      developments that link changes during gametogenesis to early embryonic
      development-a rapidly growing field that promises to bring more understanding to
      some fundamental questions regarding metazoan development.

PMID- 29378818
TI  - Carbonic anhydrase expression in the branchial ionocytes of rainbow trout.
AB  - Rainbow trout (Oncorhynchus mykiss) exposed to acid-base challenges activate
      branchial mechanisms for the excretion of acid-base equivalents. Current models
      of branchial acid-base excretion in freshwater rainbow trout propose two main
      ionocyte types: the peanut lectin agglutinin-positive (PNA+) mitochondrion-rich
      cell or ionocyte is believed to secrete HCO3- in exchange for Cl-, whereas H+
      secretion is thought to occur across PNA- ionocytes in exchange for Na+ Both HCO3
      and H+ are supplied by intracellular hydration of CO2 catalysed by cytosolic
      carbonic anhydrase (CAc). Immunohistochemical approaches revealed that under
      control conditions, CAc was detectable in 92.3+/-1.0% (N=11) of PNA- ionocytes,
      and the abundance of PNA- ionocytes increased in response to systemic acidosis
      elicited by 72 h exposure to water of low pH (nominally pH 4.5), hypercapnia (1%
      CO2, nominally 7.6 Torr) or hyperoxia (achieved by gassing water with pure O2),
      as did the abundance of PNA- ionocytes that exhibited immunofluorescence for CAc.
      However, just 4.3+/-0.6% (N=11) of PNA+ ionocytes expressed detectable CAc under
      control conditions. Marked increases in the abundance of CAc-positive PNA+
      ionocytes were detected following exposure of trout to a base load via recovery
      from hypercapnia or base infusion (72 h infusion with 140 mmol l-1 NaHCO3). The
      percentage of CAc-positive PNA+ ionocytes also was increased in trout treated
      with cortisol (10 mg kg-1 hydrocortisone 21-hemisuccinate daily for 7 days).
      These results suggest that regulation of CA within PNA+ ionocytes and/or the
      abundance of CAc-positive PNA+ ionocytes plays a role in activating base
      secretion in response to systemic alkalosis.

PMID- 29378819
TI  - Maize Transposable Elements Ac/Ds as Insertion Mutagenesis Tools in Candida
      albicans.
AB  - In nonmodel systems, genetic research is often limited by the lack of techniques
      for the generation and identification of gene mutations. One approach to overcome
      this bottleneck is the application of transposons for gene tagging. We have
      established a two-element transposon tagging system, based on the transposable
      elements Activator (Ac)/Dissociation (Ds) from maize, for in vivo insertion
      mutagenesis in the fungal human pathogen Candida albicans A nonautonomous Ds
      transposon carrying a selectable marker was constructed into the ADE2 promoter on
      chromosome 3 and a codon usage-adapted Ac transposase gene was inserted into the
      neutral NEUT5L locus on chromosome 5. In C. albicans cells expressing the
      transposase, the Ds element efficiently excised and reintegrated elsewhere in the
      genome, which makes the Ac/Ds transposons promising tools for saturating
      insertion mutagenesis in clinical strains of C. albicans.

PMID- 29378820
TI  - Genetic Loci Controlling Carotenoid Biosynthesis in Diverse Tropical Maize Lines.
AB  - The discovery and use of genetic markers associated with carotenoid levels can
      help to exploit the genetic potential of maize for provitamin A accumulation more
      effectively. Provitamin A carotenoids are classes of carotenoids that are
      precursors of vitamin A, an essential micronutrient in humans. Vitamin A
      deficiency is a global public health problem affecting millions of people,
      especially in developing countries. Maize is one of the most important staple
      crops targeted for provitamin A biofortification to help alleviate vitamin A
      deficiency in developing countries. A genome-wide association study (GWAS) of
      maize endosperm carotenoids was conducted using a panel of 130 diverse yellow
      maize tropical inbred lines genotyped with Genotyping by Sequencing (GBS) SNP
      markers. Numerous significant association signals co-localizing with the known
      carotenoid biosynthesis genes crtRB1, lcyE and ZEP1 were identified. The GWAS
      confirmed previously reported large effects of the two major carotenoid
      biosynthesis genes lcyE and crtRB1 In addition, significant novel associations
      were detected for several transcription factors (e.g., RING zinc finger domain
      and HLH DNA-binding domain super family proteins) that may be involved in
      regulation of carotenoid biosynthesis in maize. When the GWAS was re-conducted by
      including the major effects of lcyE and crtRB1 genes as covariates, a SNP in a
      gene coding for an auxin response factor 20 transcription factor was identified
      which displayed an association with beta-carotene and provitamin A levels. Our
      study provides a foundation for design and implementation of genomics-assisted
      selection strategies for provitamin A maize breeding in tropical regions, and
      advances efforts toward identification of additional genes (and allelic variants)
      involved in the regulation of carotenoid biosynthesis in plants.

PMID- 29378823
TI  - Tracing the destiny of mesenchymal stem cells from embryo to adult bone marrow
      and white adipose tissue via Pdgfralpha expression.
AB  - Mesenchymal stem cells (MSCs) are somatic stem cells that can be derived from
      adult bone marrow (BM) and white adipose tissue (WAT), and that display
      multipotency and self-renewal capacity. Although MSCs are essential for tissue
      formation and have already been used in clinical therapy, the origins and markers
      of these cells remain unknown. In this study, we first investigated the
      developmental process of MSCs in mouse embryos using the gene encoding platelet
      derived growth factor receptor alpha (Pdgfra) as a marker. We then traced cells
      expressing Pdgfra and other genes (brachyury, Sox1 and Pmx1) in various mutant
      mouse embryos until the adult stage. This tracing of MSC origins and destinies
      indicates that embryonic MSCs emerge in waves and that almost all adult BM MSCs
      and WAT MSCs originate from mesoderm and embryonic Pdgfralpha-positive cells.
      Furthermore, we demonstrate that adult Pdgfralpha-positive cells are involved in
      some pathological conditions.

PMID- 29378822
TI  - Whole-Genome Sequence Accuracy Is Improved by Replication in a Population of
      Mutagenized Sorghum.
AB  - The accurate detection of induced mutations is critical for both forward and
      reverse genetics studies. Experimental chemical mutagenesis induces relatively
      few single base changes per individual. In a complex eukaryotic genome, false
      positive detection of mutations can occur at or above this mutagenesis rate. We
      demonstrate here, using a population of ethyl methanesulfonate (EMS)-treated
      Sorghum bicolor BTx623 individuals, that using replication to detect false
      positive-induced variants in next-generation sequencing (NGS) data permits higher
      throughput variant detection with greater accuracy. We used a lower sequence
      coverage depth (average of 7*) from 586 independently mutagenized individuals and
      detected 5,399,493 homozygous single nucleotide polymorphisms (SNPs). Of these,
      76% originated from only 57,872 genomic positions prone to false positive variant
      calling. These positions are characterized by high copy number paralogs where the
      error-prone SNP positions are at copies containing a variant at the SNP position.
      The ability of short stretches of homology to generate these error-prone
      positions suggests that incompletely assembled or poorly mapped repeated
      sequences are one driver of these error-prone positions. Removal of these false
      positives left 1,275,872 homozygous and 477,531 heterozygous EMS-induced SNPs,
      which, congruent with the mutagenic mechanism of EMS, were >98% G:C to A:T
      transitions. Through this analysis, we generated a collection of sequence indexed
      mutants of sorghum. This collection contains 4035 high-impact homozygous
      mutations in 3637 genes and 56,514 homozygous missense mutations in 23,227 genes.
      Each line contains, on average, 2177 annotated homozygous SNPs per genome,
      including seven likely gene knockouts and 96 missense mutations. The number of
      mutations in a transcript was linearly correlated with the transcript length and
      also the G+C count, but not with the GC/AT ratio. Analysis of the detected
      mutagenized positions identified CG-rich patches, and flanking sequences strongly
      influenced EMS-induced mutation rates. This method for detecting false positive
      induced mutations is generally applicable to any organism, is independent of the
      choice of in silico variant-calling algorithm, and is most valuable when the true
      mutation rate is likely to be low, such as in laboratory-induced mutations or
      somatic mutation detection in medicine.

PMID- 29378825
TI  - Hunting the origins of Huntington's with human stem cells.

PMID- 29378824
TI  - Chromosomal instability during neurogenesis in Huntington's disease.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disease caused by
      expansion of CAG repeats in the Huntingtin gene (HTT). Neither its pathogenic
      mechanisms nor the normal functions of HTT are well understood. To model HD in
      humans, we engineered a genetic allelic series of isogenic human embryonic stem
      cell (hESC) lines with graded increases in CAG repeat length. Neural
      differentiation of these lines unveiled a novel developmental HD phenotype: the
      appearance of giant multinucleated telencephalic neurons at an abundance directly
      proportional to CAG repeat length, generated by a chromosomal instability and
      failed cytokinesis over multiple rounds of DNA replication. We conclude that
      disrupted neurogenesis during development is an important, unrecognized aspect of
      HD pathogenesis. To address the function of normal HTT protein we generated HTT+/
      and HTT-/- lines. Surprisingly, the same phenotype emerged in HTT-/- but not
      HTT+/- lines. We conclude that HD is a developmental disorder characterized by
      chromosomal instability that impairs neurogenesis, and that HD represents a
      genetic dominant-negative loss of function, contrary to the prevalent gain-of
      toxic-function hypothesis. The consequences of developmental alterations should
      be considered as a new target for HD therapies.

PMID- 29378826
TI  - Novel markers in the human placenta.

PMID- 29378821
TI  - Anterior Pituitary Transcriptome Suggests Differences in ACTH Release in Tame and
      Aggressive Foxes.
AB  - Domesticated species exhibit a suite of behavioral, endocrinological, and
      morphological changes referred to as "domestication syndrome." These changes may
      include a reduction in reactivity of the hypothalamic-pituitary-adrenal (HPA)
      axis and specifically reduced adrenocorticotropic hormone release from the
      anterior pituitary. To investigate the biological mechanisms targeted during
      domestication, we investigated gene expression in the pituitaries of
      experimentally domesticated foxes (Vulpes vulpes). RNA was sequenced from the
      anterior pituitary of six foxes selectively bred for tameness ("tame foxes") and
      six foxes selectively bred for aggression ("aggressive foxes"). Expression,
      splicing, and network differences identified between the two lines indicated the
      importance of genes related to regulation of exocytosis, specifically mediated by
      cAMP, organization of pseudopodia, and cell motility. These findings provide new
      insights into biological mechanisms that may have been targeted when these lines
      of foxes were selected for behavior and suggest new directions for research into
      HPA axis regulation and the biological underpinnings of domestication.

PMID- 29378828
TI  - Import of TAT-Conjugated Propionyl Coenzyme A Carboxylase Using Models of
      Propionic Acidemia.
AB  - Propionic acidemia is caused by a deficiency of the enzyme propionyl coenzyme A
      carboxylase (PCC) located in the mitochondrial matrix. Cell-penetrating peptides,
      including transactivator of transcription (TAT), offer a potential to deliver a
      cargo into the mitochondrion. Here, we investigated the delivery of an
      alpha6beta6 PCC enzyme into mitochondria using the HIV TAT peptide at several
      levels: into isolated mitochondria, in patient fibroblast cells, and in a mouse
      model. Results from Western blots and enzyme activity assays confirmed the import
      of TAT-PCC into mitochondria, as well as into patient fibroblasts, where the
      colocalization of imported TAT-PCC and mitochondria was also confirmed by
      confocal fluorescence microscopy. Furthermore, a single-dose intraperitoneal
      injection into PCC-deficient mice decreased the
      propionylcarnitine/acetylcarnitine (C3/C2) ratio toward the normal level. These
      results show that a cell-penetrating peptide can deliver active multimeric enzyme
      into mitochondria in vitro, in situ, and in vivo and push the size limit of
      intracellular delivery achieved so far. Our results are promising for other
      mitochondrion-specific deficiencies.

PMID- 29378827
TI  - Cilium Length and Intraflagellar Transport Regulation by Kinases PKG-1 and GCK-2
      in Caenorhabditis elegans Sensory Neurons.
AB  - To understand how ciliopathies such as polycystic kidney disease or Bardet-Biedl
      syndrome develop, we need to understand the basic molecular mechanisms underlying
      cilium development. Cilium growth depends on the presence of functional
      intraflagellar transport (IFT) machinery, and we hypothesized that various
      kinases and phosphatases might be involved in this regulatory process. A
      candidate screen revealed two kinases, PKG-1 (a cGMP-dependent protein kinase)
      and GCK-2 (a mitogen-activated protein kinase kinase kinase kinase 3 [MAP4K3]
      kinase involved in mTOR signaling), significantly affecting dye filling,
      chemotaxis, cilium morphology, and IFT component distribution. PKG-1 and GCK-2
      show similar expression patterns in Caenorhabditis elegans cilia and colocalize
      with investigated IFT machinery components. In pkg-1 mutants, a high level of
      accumulation of kinesin-2 OSM-3 in distal segments was observed in conjunction
      with an overall reduction of anterograde and retrograde IFT particle A transport,
      likely as a function of reduced tubulin acetylation. In contrast, in gck-2
      mutants, both kinesin-2 motility and IFT particle A motility were significantly
      elevated in the middle segments, in conjunction with increased tubulin
      acetylation, possibly the cause of longer cilium growth. Observed effects in
      mutants can be also seen in manipulating upstream and downstream effectors of the
      respective cGMP and mTOR pathways. Importantly, transmission electron microscopy
      (TEM) analysis revealed no structural changes in cilia of pkg-1 and gck-2
      mutants.

PMID- 29378829
TI  - Regulation of Cholesterol Sulfotransferase SULT2B1b by Hepatocyte Nuclear Factor
      4alpha Constitutes a Negative Feedback Control of Hepatic Gluconeogenesis.
AB  - The cholesterol sulfotransferase SULT2B1b converts cholesterol to cholesterol
      sulfate (CS). We previously reported that SULT2B1b inhibits hepatic
      gluconeogenesis by antagonizing the gluconeogenic activity of hepatocyte nuclear
      factor 4alpha (HNF4alpha). In this study, we showed that the SULT2B1b gene is a
      transcriptional target of HNF4alpha, which led to our hypothesis that the
      induction of SULT2B1b by HNF4alpha represents a negative feedback to limit the
      gluconeogenic activity of HNF4alpha. Indeed, downregulation of Sult2B1b enhanced
      the gluconeogenic activity of HNF4alpha, which may have been accounted for by the
      increased acetylation of HNF4alpha as a result of decreased expression of the
      HNF4alpha deacetylase sirtuin 1 (Sirt1). The expression of Sult2B1b was also
      induced by HNF4alpha upon fasting, and the Sult2B1b null (Sult2B1b-/-) mice
      showed increased gluconeogenic gene expression and an elevated fasting glucose
      level, suggesting that SULT2B1b also plays a restrictive role in HNF4alpha
      mediated fasting-responsive gluconeogenesis. We also developed thiocholesterol, a
      hydrolysis-resistant derivative of CS, which showed superior activity to that of
      the native CS in inhibiting gluconeogenesis and improving insulin sensitivity in
      high-fat-diet-induced diabetic mice. We conclude that the HNF4alpha-SULT2B1b-CS
      axis represents a key endogenous mechanism to prevent uncontrolled
      gluconeogenesis. Thiocholesterol may be used as a therapeutic agent to manage
      hyperglycemia.

PMID- 29378830
TI  - 53BP1 Mediates ATR-Chk1 Signaling and Protects Replication Forks under Conditions
      of Replication Stress.
AB  - Complete replication of the genome is an essential prerequisite for normal cell
      division, but a variety of factors can block the replisome, triggering
      replication stress and potentially causing mutation or cell death. The cellular
      response to replication stress involves recruitment of proteins to stabilize the
      replication fork and transmit a stress signal to pause the cell cycle and allow
      fork restart. We find that the ubiquitously expressed DNA damage response factor
      53BP1 is required for the normal response to replication stress. Using primary,
      ex vivo B cells, we showed that a population of 53BP1-/- cells in early S phase
      is hypersensitive to short-term exposure to three different agents that induce
      replication stress. 53BP1 localizes to a subset of replication forks following
      induced replication stress, and an absence of 53BP1 leads to defective ATR-Chk1
      p53 signaling and caspase 3-mediated cell death. Nascent replicated DNA
      additionally undergoes degradation in 53BP1-/- cells. These results show that
      53BP1 plays an important role in protecting replication forks during the cellular
      response to replication stress, in addition to the previously characterized role
      of 53BP1 in DNA double-strand break repair.

PMID- 29378831
TI  - Cation-Independent Mannose 6-Phosphate Receptor Deficiency Enhances beta-Cell
      Susceptibility to Palmitate.
AB  - Palmitate attenuates insulin secretion and reduces the viability of insulin
      producing cells. Previous studies identified the aberrant palmitoylation or
      mispalmitoylation of proteins as one mechanism by which palmitate causes beta
      cell damage. In this report, we identify a role for lysosomal protein degradation
      as a mechanism by which beta cells defend themselves against excess palmitate.
      The cation-independent mannose 6-phosphate receptor (CI-MPR) is responsible for
      the trafficking of mannose 6-phosphate-tagged proteins to lysosomes via Golgi
      sorting and from extracellular locations through endocytosis. RINm5F cells, which
      are highly sensitive to palmitate, lack CI-MPR. The reconstitution of CI-MPR
      expression attenuates the induction of endoplasmic reticulum (ER) stress and the
      toxic effects of palmitate on RINm5F cell viability. INS832/13 cells express CI
      MPR and are resistant to the palmitate-mediated loss of cell viability. The
      reduction of CI-MPR expression increases the sensitivity of INS832/13 cells to
      the toxic effects of palmitate treatment. The inhibition of lysosomal acid
      hydrolase activity by weak base treatment of islets under glucolipotoxic
      conditions causes islet degeneration that is prevented by the inhibition of
      protein palmitoylation. These findings indicate that defects in lysosomal
      function lead to the enhanced sensitivity of insulin-producing cells to palmitate
      and support a role for normal lysosomal function in the protection of beta cells
      from excess palmitate.

PMID- 29378832
TI  - Membrane Trafficking Protein CDP138 Regulates Fat Browning and Insulin
      Sensitivity through Controlling Catecholamine Release.
AB  - CDP138 is a calcium- and lipid-binding protein that is involved in membrane
      trafficking. Here we report mice without CDP138 develop obesity under normal chow
      diet (NCD) or high-fat diet (HFD) conditions. CDP138-/- mice have lower energy
      expenditure, oxygen consumption and body temperature in comparison with wild-type
      (WT) mice. CDP138 is exclusively expressed in adrenal medulla and is co-localized
      with tyrosine hydroxylase (TH), a marker of sympathetic nervous terminals, in the
      inguinal fat. In comparison with WT controls, CDP138-/- mice had altered
      catecholamine levels in the circulation, adrenal grand, and inguinal fat.
      Adrenergic signaling on cyclic adenosine monophosphate (cAMP) formation and
      hormone sensitive lipase (HSL) phosphorylation induced by cold challenge, but not
      by an exogenous beta3 adrenoceptor against CL316243, were decreased in adipose
      tissues of CDP138-/- mice. Cold-induced beige fat browning, fatty acid oxidation,
      thermogenesis, and related gene expression were reduced in CDP138-/- mice. CDP138
      /- mice are also prone to HFD-induced insulin resistance assessed by Akt
      phosphorylation and glucose transport in skeletal muscles. Our data indicates
      that CDP138 is a regulator of stress response and plays a significant role in
      adipose tissue browning, energy balance, and insulin sensitivity through
      regulating catecholamine secretion from the sympathetic nervous terminals and
      adrenal gland.

PMID- 29378834
TI  - Building a plant cell wall at a glance.
AB  - Plant cells are surrounded by a strong polysaccharide-rich cell wall that aids in
      determining the overall form, growth and development of the plant body. Indeed,
      the unique shapes of the 40-odd cell types in plants are determined by their
      walls, as removal of the cell wall results in spherical protoplasts that are
      amorphic. Hence, assembly and remodeling of the wall is essential in plant
      development. Most plant cell walls are composed of a framework of cellulose
      microfibrils that are cross-linked to each other by heteropolysaccharides. The
      cell walls are highly dynamic and adapt to the changing requirements of the plant
      during growth. However, despite the importance of plant cell walls for plant
      growth and for applications that we use in our daily life such as food, feed and
      fuel, comparatively little is known about how they are synthesized and modified.
      In this Cell Science at a Glance article and accompanying poster, we aim to
      illustrate the underpinning cell biology of the synthesis of wall carbohydrates,
      and their incorporation into the wall, in the model plant Arabidopsis.

PMID- 29378835
TI  - Chemical signaling for pollen tube guidance at a glance.
AB  - Pollen tube guidance is a unique navigating system that is required for the
      successful sexual reproduction of plants. As plant sperm cells are non-motile and
      egg cells are embedded deep inside the female tissues, a pollen tube delivers the
      two sperm cells that it contains by growing towards the ovule, in which the egg
      cell resides. Pollen tube growth towards the ovule is precisely controlled and
      divided into two stages, preovular and ovular guidance. In this Cell Science at a
      Glance article and accompanying poster, we provide a comprehensive overview of
      pollen tube guidance and highlight some of the attractant peptides used during
      ovular guidance. We further discuss the precise one-to-one guidance system that
      exists in multi-ovular plants. The pollen tube-blocking system, which is mediated
      by male-female crosstalk communication, to avoid attraction of multiple pollen
      tubes, is also reviewed.

PMID- 29378833
TI  - MafB Is Critical for Glucagon Production and Secretion in Mouse Pancreatic alpha
      Cells In Vivo.
AB  - The MafB transcription factor is expressed in pancreatic alpha and beta cells
      during development but becomes exclusive to alpha cells in adult rodents. Mafb
      null (Mafb-/- ) mice were reported to have reduced alpha- and beta-cell numbers
      throughout embryonic development. To further analyze the postnatal function of
      MafB in the pancreas, we generated endocrine cell-specific (MafbDeltaEndo ) and
      tamoxifen-dependent (MafbDeltaTAM ) Mafb knockout mice. MafbDeltaEndo mice
      exhibited reduced populations of insulin-positive (insulin+) and glucagon+ cells
      at postnatal day 0, but the insulin+ cell population recovered by 8 weeks of age.
      In contrast, the Arx+ glucagon+ cell fraction and glucagon expression remained
      decreased even in adulthood. MafbDeltaTAM mice, with Mafb deleted after pancreas
      maturation, also demonstrated diminished glucagon+ cells and glucagon content
      without affecting beta cells. A decreased Arx+ glucagon+ cell population in
      MafbDeltaEndo mice was compensated for by an increased Arx+ pancreatic
      polypeptide+ cell population. Furthermore, gene expression analyses from both
      MafbDeltaEndo and MafbDeltaTAM islets revealed that MafB is a key regulator of
      glucagon expression in alpha cells. Finally, both mutants failed to respond to
      arginine, likely due to impaired arginine transporter gene expression and
      glucagon production ability. Taken together, our findings reveal that MafB is
      critical for the functional maintenance of mouse alpha cells in vivo, including
      glucagon production and secretion, as well as in development.

PMID- 29378836
TI  - Plant cell surface receptor-mediated signaling - a common theme amid diversity.
AB  - Sessile plants employ a diverse array of plasma membrane-bound receptors to
      perceive endogenous and exogenous signals for regulation of plant growth,
      development and immunity. These cell surface receptors include receptor-like
      kinases (RLKs) and receptor-like proteins (RLPs) that harbor different
      extracellular domains for perception of distinct ligands. Several RLK and RLP
      signaling pathways converge at the somatic embryogenesis receptor kinases
      (SERKs), which function as shared co-receptors. A repertoire of receptor-like
      cytoplasmic kinases (RLCKs) associate with the receptor complexes to relay
      intracellular signaling. Downstream of the receptor complexes, mitogen-activated
      protein kinase (MAPK) cascades are among the key signaling modules at which the
      signals converge, and these cascades regulate diverse cellular and physiological
      responses through phosphorylation of different downstream substrates. In this
      Review, we summarize the emerging common theme that underlies cell surface
      receptor-mediated signaling pathways in Arabidopsisthaliana: the dynamic
      association of RLKs and RLPs with specific co-receptors and RLCKs for signal
      transduction. We further discuss how signaling specificities are maintained
      through modules at which signals converge, with a focus on SERK-mediated receptor
      signaling.

PMID- 29378837
TI  - Actin-mediated movement of chloroplasts.
AB  - Plants are sessile and require diverse strategies to adapt to fluctuations in the
      surrounding light conditions. Consequently, the photorelocation movement of
      chloroplasts is essential to prevent damages that are induced by intense light
      (avoidance response) and to ensure efficient photosynthetic activities under weak
      light conditions (accumulation response). The mechanisms that underlie
      chloroplast movements have been revealed through analysis of the behavior of
      individual chloroplasts and it has been found that these organelles can move in
      any direction without turning. This implies that any part of the chloroplast
      periphery can function as the leading or trailing edge during movement. This
      ability is mediated by a special structure, which consists of short actin
      filaments that are polymerized at the leading edge of moving chloroplasts and are
      specifically localized in the space between the chloroplast and the plasma
      membrane, and is called chloroplast-actin. In addition, several of the genes that
      encode proteins that are involved in chloroplast-actin polymerization or
      maintenance have been identified. In this Review, we discuss the mechanisms that
      regulate chloroplast movements through polymerization of the chloroplast-actin
      and propose a model for actin-driven chloroplast photorelocation movement.

PMID- 29378841
TI  - Have plant cells been forgotten?

PMID- 29378843
TI  - Interview with the Guest Editor - Jenny Russinova.
AB  - Jenny Russinova graduated in biotechnology from the University of Sofia,
      Bulgaria, and subsequently obtained her PhD at De Montfort University, Leicester,
      UK, where she worked on gene expression in plant embryogenesis. Jenny then moved
      to the Netherlands to do her post-doctoral studies at Wageningen University,
      Wageningen, in the laboratory of Sacco de Vries. There, she worked on cellular
      regulation, mechanisms and localization of plant receptor-like kinases. In 2006,
      she started her own research group at the Vlaams Instituut voor Biotechnologie
      (VIB) at Ghent University, Belgium, focusing on brassinosteroid signaling
      regulation in plants. Jenny is the Guest Editor for the 2018 plant cell biology
      Special Issue in Journal of Cell Science.

PMID- 29378844
TI  - Protein arginine methyltransferase 7-mediated microRNA-221 repression maintains
      Oct4, Nanog, and Sox2 levels in mouse embryonic stem cells.
AB  - The stemness maintenance of embryonic stem cells (ESCs) requires pluripotency
      transcription factors, including Oct4, Nanog, and Sox2. We have previously
      reported that protein arginine methyltransferase 7 (PRMT7), an epigenetic
      modifier, is an essential pluripotency factor that maintains the stemness of
      mouse ESCs, at least in part, by down-regulating the expression of the anti
      stemness microRNA (miRNA) miR-24-2. To gain greater insight into the molecular
      basis underlying PRMT7-mediated maintenance of mouse ESC stemness, we searched
      for new PRMT7-down-regulated anti-stemness miRNAs. Here, we show that miR-221
      gene-encoded miR-221-3p and miR-221-5p are anti-stemness miRNAs whose expression
      levels in mouse ESCs are directly repressed by PRMT7. Notably, both miR-221-3p
      and miR-221-5p targeted the 3' untranslated regions of mRNA transcripts of the
      major pluripotency factors Oct4, Nanog, and Sox2 to antagonize mouse ESC
      stemness. Moreover, miR-221-5p silenced also the expression of its own
      transcriptional repressor PRMT7. Transfection of miR-221-3p and miR-221-5p mimics
      induced spontaneous differentiation of mouse ESCs. CRISPR-mediated deletion of
      the miR-221 gene, as well as specific antisense inhibitors of miR-221-3p and miR
      221-5p, inhibited the spontaneous differentiation of PRMT7-depleted mouse ESCs.
      Taken together, these findings reveal that the PRMT7-mediated repression of miR
      221-3p and miR-221-5p expression plays a critical role in maintaining mouse ESC
      stemness. Our results also establish miR-221-3p and miR-221-5p as anti-stemness
      miRNAs that target Oct4, Nanog, and Sox2 mRNAs in mouse ESCs.

PMID- 29378845
TI  - Estrogen receptor alpha protects pancreatic beta-cells from apoptosis by
      preserving mitochondrial function and suppressing endoplasmic reticulum stress.
AB  - Estrogen receptor alpha (ERalpha) action plays an important role in pancreatic
      beta-cell function and survival; thus, it is considered a potential therapeutic
      target for the treatment of type 2 diabetes in women. However, the mechanisms
      underlying the protective effects of ERalpha remain unclear. Because ERalpha
      regulates mitochondrial metabolism in other cell types, we hypothesized that
      ERalpha may act to preserve insulin secretion and promote beta-cell survival by
      regulating mitochondrial-endoplasmic reticulum (EndoRetic) function. We tested
      this hypothesis using pancreatic islet-specific ERalpha knockout (PERalphaKO)
      mice and Min6 beta-cells in culture with Esr1 knockdown (KD). We found that Esr1
      KD promoted reactive oxygen species production that associated with reduced
      fission/fusion dynamics and impaired mitophagy. Electron microscopy showed
      mitochondrial enlargement and a pro-fusion phenotype. Mitochondrial cristae and
      endoplasmic reticulum were dilated in Esr1-KD compared with ERalpha replete Min6
      beta-cells. Increased expression of Oma1 and Chop was paralleled by increased
      oxygen consumption and apoptosis susceptibility in ERalpha-KD cells. In contrast,
      ERalpha overexpression and ligand activation reduced both Chop and Oma1
      expression, likely by ERalpha binding to consensus estrogen-response element
      sites in the Oma1 and Chop promoters. Together, our findings suggest that ERalpha
      promotes beta-cell survival and insulin secretion through maintenance of
      mitochondrial fission/fusion-mitophagy dynamics and EndoRetic function, in part
      by Oma1 and Chop repression.

PMID- 29378846
TI  - Single-cell nanobiopsy reveals compartmentalization of mRNAs within neuronal
      cells.
AB  - In highly polarized cells such as neurons, compartmentalization of mRNA and of
      local protein synthesis enables remarkably fast, precise, and local responses to
      external stimuli. These responses are highly important for neuron growth cone
      guidance, synapse formation, and regeneration following injury. Because an
      altered spatial distribution of mRNA can result in mental retardation or
      neurodegenerative diseases, subcellular transcriptome analysis of neurons could
      be a useful tool for studying these conditions, but current techniques, such as
      in situ hybridization, bulk microarray, and RNA-Seq, impose tradeoffs between
      spatial resolution and multiplexing. To obtain a comprehensive analysis of the
      cell body versus neurite transcriptome from the same neuron, we have recently
      developed a label-free, single-cell nanobiopsy platform based on scanning ion
      conductance microscopy that uses electrowetting within a quartz nanopipette to
      extract cellular material from living cells with minimal disruption of the
      cellular membrane and milieu. In this study, we used this platform to collect
      samples from the cell bodies and neurites of human neurons and analyzed the mRNA
      pool with multiplex RNA sequencing. The minute volume of a nanobiopsy sample
      allowed us to extract samples from several locations in the same cell and to map
      the various mRNA species to specific subcellular locations. In addition to
      previously identified transcripts, we discovered new sets of mRNAs localizing to
      neurites, including nuclear genes such as Eomes and Hmgb3 In summary, our single
      neuron nanobiopsy analysis provides opportunities to improve our understanding of
      intracellular mRNA transport and local protein composition in neuronal growth,
      connectivity, and function.

PMID- 29378847
TI  - Nudt19 is a renal CoA diphosphohydrolase with biochemical and regulatory
      properties that are distinct from the hepatic Nudt7 isoform.
AB  - CoA is the major acyl carrier in mammals and a key cofactor in energy metabolism.
      Dynamic regulation of CoA in different tissues and organs supports metabolic
      flexibility. Two mammalian Nudix hydrolases, Nudt19 and Nudt7, degrade CoA in
      vitro Nudt19 and Nudt7 possess conserved Nudix and CoA signature sequences and
      specifically hydrolyze the diphosphate bond of free CoA and acyl-CoAs to form
      3',5'-ADP and 4'-(acyl)phosphopantetheine. Limited information is available on
      these enzymes, but the relatively high abundance of Nudt19 and Nudt7 mRNA in the
      kidney and liver, respectively, suggests that they play specific roles in the
      regulation of CoA levels in these organs. Here, we analyzed Nudt19-/- mice and
      found that deletion of Nudt19 elevates kidney CoA levels in mice fed ad libitum,
      indicating that Nudt19 contributes to the regulation of CoA in vivo Unlike what
      was observed for the regulation of Nudt7 in the liver, Nudt19 transcript and
      protein levels in the kidney did not differ between fed and fasted states.
      Instead, we identified chenodeoxycholic acid as a specific Nudt19 inhibitor that
      competed with CoA for Nudt19 binding but did not bind to Nudt7. Exchange of the
      Nudix and CoA signature motifs between the two isoforms dramatically decreased
      their kcat Furthermore, substitutions of conserved residues within these motifs
      identified amino acids playing different roles in CoA binding and hydrolysis in
      Nudt19 and Nudt7. Our results reveal that the kidney and liver each possesses a
      distinct peroxisomal CoA diphosphohydrolase.

PMID- 29378848
TI  - A major isoform of the E3 ubiquitin ligase March-I in antigen-presenting cells
      has regulatory sequences within its gene.
AB  - Regulation of major histocompatibility complex class II (MHC-II) expression is
      important not only to maintain a diverse pool of MHC-II-peptide complexes but
      also to prevent development of autoimmunity. The membrane-associated RING-CH
      (March) E3 ubiquitin ligase March-I regulates ubiquitination and turnover of MHC
      II-peptide complexes in resting dendritic cells (DCs) and B cells. However,
      activation of either cell type terminates March-I expression, thereby stabilizing
      MHC-II-peptide complexes. Despite March-I's important role in the biology of
      antigen-presenting cells (APCs), how expression of March-I mRNA is regulated
      remains unknown. We now show that both DCs and B cells possess a distinct isoform
      of March-I whose expression is regulated by a promoter located within the March-I
      gene. Using March-I promoter fragments to drive expression of GFP, we also
      identified a core promoter for expression of March-I in DCs and B cells, but not
      in fibroblasts, kidney cells, or epithelial cells, that contains regulatory
      regions that down-regulate March-I expression upon activation of DCs. Curiously,
      we found downstream sequence elements, present in the first coding exon of March
      I in APCs, that confer regulation of March-I expression in activated APCs. In
      summary, our study identifies regulatory regions of the March-I gene that confer
      APC-specific expression and activation-induced modulation of March-I expression
      in DCs and B cells.

PMID- 29378849
TI  - Drosophila melanogaster Guk-holder interacts with the Scribbled PDZ1 domain and
      regulates epithelial development with Scribbled and Discs Large.
AB  - Epithelial cell polarity is controlled by components of the Scribble polarity
      module, and its regulation is critical for tissue architecture and cell
      proliferation and migration. In Drosophila melanogaster, the adaptor protein Guk
      holder (Gukh) binds to the Scribbled (Scrib) and Discs Large (Dlg) components of
      the Scribble polarity module and plays an important role in the formation of
      neuromuscular junctions. However, Gukh's role in epithelial tissue formation and
      the molecular basis for the Scrib-Gukh interaction remain to be defined. We now
      show using isothermal titration calorimetry that the Scrib PDZ1 domain is the
      major site for an interaction with Gukh. Furthermore, we defined the structural
      basis of this interaction by determining the crystal structure of the Scrib PDZ1
      Gukh complex. The C-terminal PDZ-binding motif of Gukh is located in the
      canonical ligand-binding groove of Scrib PDZ1 and utilizes an unusually extensive
      network of hydrogen bonds and ionic interactions to enable binding to PDZ1 with
      high affinity. We next examined the role of Gukh along with those of Scrib and
      Dlg in Drosophila epithelial tissues and found that Gukh is expressed in larval
      wing and eye-epithelial tissues and co-localizes with Scrib and Dlg at the apical
      cell cortex. Importantly, we show that Gukh functions with Scrib and Dlg in the
      development of Drosophila epithelial tissues, with depletion of Gukh enhancing
      the eye- and wing-tissue defects caused by Scrib or Dlg depletion. Overall, our
      findings reveal that Scrib's PDZ1 domain functions in the interaction with Gukh
      and that the Scrib-Gukh interaction has a key role in epithelial tissue
      development in Drosophila.

PMID- 29378850
TI  - A statistical model for improved membrane protein expression using sequence
      derived features.
AB  - The heterologous expression of integral membrane proteins (IMPs) remains a major
      bottleneck in the characterization of this important protein class. IMP
      expression levels are currently unpredictable, which renders the pursuit of IMPs
      for structural and biophysical characterization challenging and inefficient.
      Experimental evidence demonstrates that changes within the nucleotide or amino
      acid sequence for a given IMP can dramatically affect expression levels, yet
      these observations have not resulted in generalizable approaches to improve
      expression levels. Here, we develop a data-driven statistical predictor named
      IMProve that, using only sequence information, increases the likelihood of
      selecting an IMP that expresses in Escherichia coli The IMProve model, trained on
      experimental data, combines a set of sequence-derived features resulting in an
      IMProve score, where higher values have a higher probability of success. The
      model is rigorously validated against a variety of independent data sets that
      contain a wide range of experimental outcomes from various IMP expression trials.
      The results demonstrate that use of the model can more than double the number of
      successfully expressed targets at any experimental scale. IMProve can immediately
      be used to identify favorable targets for characterization. Most notably, IMProve
      demonstrates for the first time that IMP expression levels can be predicted
      directly from sequence.

PMID- 29378852
TI  - Socioeconomic Status and Hypertension Control in Sub-Saharan Africa: The
      Multination EIGHT Study (Evaluation of Hypertension in Sub-Saharan Africa).
AB  - Systemic hypertension is a rapidly growing epidemic in Africa. The role of
      socioeconomic status on blood pressure control has not been well studied in this
      part of the world. We, therefore, aimed to quantify the association of
      socioeconomic status both at the individual and at the country level with blood
      pressure control in Sub-Saharan Africa. We conducted a cross-sectional survey in
      urban clinics of 12 countries, both low income and middle income, in Sub-Saharan
      Africa. Standardized blood pressure measures were made among the hypertensive
      patients attending the clinics. Blood pressure control was defined as blood
      pressure <140/90 mm Hg, and hypertension grades were defined according to the
      European Society of Cardiology guidelines. A total of 2198 hypertensive patients
      (58.4+/-11.8 years; 39.9% men) were included. Uncontrolled hypertension was
      present in 1692 patients (77.4%), including 1044 (47.7%) with >=grade 2
      hypertension. The proportion of uncontrolled hypertension progressively increased
      with decreasing level of patient individual wealth, respectively, 72.8%, 79.3%,
      and 81.8% (P for trend, <0.01). Stratified analysis shows that these differences
      of uncontrolled hypertension according to individual wealth index were observed
      in low-income countries (P for trend, 0.03) and not in middle-income countries (P
      for trend, 0.26). In low-income countries, the odds of uncontrolled hypertension
      increased 1.37-fold (odds ratio, 1.37 [0.99-1.90]) and 1.88-fold (odds ratio,
      1.88 [1.10-3.21]) in patients with middle and low individual wealth as compared
      with high individual wealth. Similarly, the grade of hypertension increased
      progressively with decreasing level of individual patient wealth (P for trend,
      <0.01). Strategies for hypertension control in Sub-Saharan Africa should
      especially focus on people in the lowest individual wealth groups who also reside
      in low-income countries.

PMID- 29378851
TI  - Phosphorylation of protein kinase A (PKA) regulatory subunit RIalpha by protein
      kinase G (PKG) primes PKA for catalytic activity in cells.
AB  - cAMP-dependent protein kinase (PKAc) is a pivotal signaling protein in eukaryotic
      cells. PKAc has two well-characterized regulatory subunit proteins, RI and RII
      (each having alpha and beta isoforms), which keep the PKAc catalytic subunit in a
      catalytically inactive state until activation by cAMP. Previous reports showed
      that the RIalpha regulatory subunit is phosphorylated by cGMP-dependent protein
      kinase (PKG) in vitro, whereupon phosphorylated RIalpha no longer inhibits PKAc
      at normal (1:1) stoichiometric ratios. However, the significance of this
      phosphorylation as a mechanism for activating type I PKA holoenzymes has not been
      fully explored, especially in cellular systems. In this study, we further
      examined the potential of RIalpha phosphorylation to regulate physiologically
      relevant "desensitization" of PKAc activity. First, the serine 101 site of
      RIalpha was validated as a target of PKGIalpha phosphorylation both in vitro and
      in cells. Analysis of a phosphomimetic substitution in RIalpha (S101E) showed
      that modification of this site increases PKAc activity in vitro and in cells,
      even without cAMP stimulation. Numerous techniques were used to show that
      although Ser101 variants of RIalpha can bind PKAc, the modified linker region of
      the S101E mutant has a significantly reduced affinity for the PKAc active site.
      These findings suggest that RIalpha phosphorylation may be a novel mechanism to
      circumvent the requirement of cAMP stimulus to activate type I PKA in cells. We
      have thus proposed a model to explain how PKG phosphorylation of RIalpha creates
      a "sensitized intermediate" state that is in effect primed to trigger PKAc
      activity.

PMID- 29378853
TI  - Left Ventricular Hypertrophy and Remodeling and Risk of Cognitive Impairment and
      Dementia: MESA (Multi-Ethnic Study of Atherosclerosis).
AB  - Limited information exists on the longitudinal association between the left
      ventricular (LV) structure and function and future cognitive impairment and
      dementia in a large population without clinically recognized cardiovascular
      disease at baseline. The aim of the present study was to investigate the
      association between cardiac structure and function and risk of dementia and
      cognitive impairment in the MESA (Multi-Ethnic Study of Atherosclerosis) cohort.
      Measures of LV structure and function were determined using magnetic resonance
      imaging at baseline in 4999 participants free of clinically diagnosed
      cardiovascular disease and dementia. Probable incident clinical dementia was
      ascertained from hospitalization discharge records. Cognitive function was
      evaluated using tests addressing global cognitive function, processing speed, and
      memory. Associations of measures of LV structure and function with the incidence
      of clinically diagnosed dementia and cognitive performance were evaluated using
      Cox proportional hazard regression models adjusted for demographics,
      cardiovascular risk factors, and cardiovascular events. During a median follow-up
      of 12 years, 130 probable incident dementia cases were documented. Higher LV mass
      index (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02) and LV mass-to
      volume ratio (hazard ratio, 2.37; 95% confidence interval, 1.25-4.43) were
      independently associated with incident dementia and impaired cognitive function.
      Measures of LV function were not associated with risk of dementia or cognitive
      impairment. In conclusion, in a multiethnic cohort of participants without
      clinically detected cardiovascular disease and dementia at baseline, LV
      hypertrophy and concentric remodeling were independently associated with incident
      dementia and cognitive impairment.

PMID- 29378854
TI  - Dysregulated Expression of RPS4Y1 (Ribosomal Protein S4, Y-Linked 1) Impairs
      STAT3 (Signal Transducer and Activator of Transcription 3) Signaling to Suppress
      Trophoblast Cell Migration and Invasion in Preeclampsia.
AB  - Normal placentation and a successful pregnancy depend on appropriate trophoblast
      cell migration and invasion. Inadequate trophoblast invasion and impaired spiral
      artery remodeling may lead to pregnancy-related disorders, such as preeclampsia.
      RPS4Y1 (ribosomal protein S4, Y-linked 1) is a member of the S4E family of
      ribosomal proteins. In this study, we found that RPS4Y1 levels were upregulated
      in placental samples collected from preeclamptic patients, when compared with the
      normotensive pregnant women. In vitro, inhibition of RPS4Y1 induced trophoblast
      cell invasion, promoted placental explant outgrowth, and increased STAT3 (signal
      transducer and activator of transcription 3) phosphorylation along with elevated
      expression of N-cadherin and vimentin. Conversely, overexpression of RPS4Y1
      results in reduced trophoblast cell invasion and decreased STAT3 phosphorylation.
      In addition, the suppression of RPS4Y1 promotes trophoblast cell invasion, which
      could be abolished by the STAT3 knockdown. Meanwhile, we observed reductions of
      STAT3 phosphorylation expression in preeclampsia patients. Collectively, these
      results demonstrate that the level of RPS4Y1 expression may be associated with
      preeclampsia by affecting trophoblast cell migration and invasion via the
      STAT3/epithelial-mesenchymal transition pathway.

PMID- 29378855
TI  - Parameters of Left Ventricular Mass and Dementia: Moving the Literature Forward.

PMID- 29378856
TI  - Under Pressure: A New Role for CD11c+ Myeloid Cells in Hypertension.

PMID- 29378857
TI  - Myeloid CD11c+ Antigen-Presenting Cells Ablation Prevents Hypertension in
      Response to Angiotensin II Plus High-Salt Diet.
AB  - Increasing evidence shows that antigen-presenting cells (APCs) are involved in
      the development of inflammation associated to hypertension. However, the
      potential role of APCs in the modulation of renal sodium transport has not been
      addressed. We hypothesized that APCs participate in renal sodium transport and,
      thus, development of high blood pressure in response to angiotensin II plus a
      high-salt diet. Using transgenic mice that allow the ablation of CD11chigh APCs,
      we studied renal sodium transport, the intrarenal renin-angiotensin system
      components, blood pressure, and cardiac/renal tissue damage in response to
      angiotensin II plus a high-salt diet. Strikingly, we found that APCs are required
      for the development of hypertension and that the ablation/restitution of APCs
      produces rapid changes in the blood pressure in mice with angiotensin II plus a
      high-salt diet. Moreover, APCs were necessary for the induction of intrarenal
      renin-angiotensin system components and affected the modulation of natriuresis
      and tubular sodium transporters. Consistent with the prevention of hypertension,
      the ablation of APCs also prevented cardiac hypertrophy and the induction of
      several indicators of renal and cardiac damage. Thus, our findings indicate a
      prominent role of APCs as modulators of blood pressure by mechanisms including
      renal sodium handling, with kinetics that suggest the involvement of tubular cell
      functions in addition to the modulation of inflammation and adaptive immune
      response.

PMID- 29378858
TI  - Plasma Cell Depletion Attenuates Hypertension in an Experimental Model of
      Autoimmune Disease.
AB  - Numerous studies show a direct relation between circulating autoantibodies,
      characteristic of systemic autoimmune disorders, and primary hypertension in
      humans. Whether these autoantibodies mechanistically contribute to the
      development of hypertension remains unclear. Systemic lupus erythematosus (SLE)
      is a chronic autoimmune disorder characterized by aberrant immunoglobulin
      production, notably pathogenic autoantibodies, and is associated with prevalent
      hypertension, renal injury, and cardiovascular disease. Because plasma cells
      produce the majority of serum immunoglobulins and are the primary source of
      autoantibodies in SLE, we hypothesized that plasma cell depletion using the
      proteasome inhibitor bortezomib would lower autoantibody production and attenuate
      hypertension. Thirty-week-old female SLE (NZBWF1) and control (NZW [New Zealand
      White]) mice were injected IV with vehicle (0.9% saline) or bortezomib (0.75
      mg/kg) twice weekly for 4 weeks. Bortezomib treatment significantly lowered the
      percentage of bone marrow plasma cells in SLE mice. Total plasma IgG and anti
      dsDNA IgG levels were higher in SLE mice compared with control mice but were
      lowered by bortezomib treatment. Mean arterial pressure (mm Hg) measured in
      conscious mice by carotid artery catheter was higher in SLE mice than in control
      mice, but mean arterial pressure was significantly lower in bortezomib-treated
      SLE mice. Bortezomib also attenuated renal injury, as assessed by albuminuria and
      glomerulosclerosis, and reduced glomerular immunoglobulin deposition and B and T
      lymphocytes infiltration into the kidneys. Taken together, these data show that
      the production of autoantibodies by plasma cells mechanistically contributes to
      autoimmune-associated hypertension and suggests a potential role for patients
      with primary hypertension who have increased circulating immunoglobulins.

PMID- 29378859
TI  - High prevalence of latent tuberculosis and bloodborne virus infection in a
      homeless population.
AB  - INTRODUCTION: Urban homeless populations in the UK have been shown to have high
      rates of active tuberculosis, but less is known about the prevalence of latent
      tuberculosis infection (LTBI). This study aimed to estimate the prevalence of
      LTBI among individuals using homeless hostels in London. METHODS: We performed a
      cross-sectional survey with outcome follow-up in homeless hostels in London. Our
      primary outcome was prevalence of LTBI. Recruitment for the study took place
      between May 2011 and June 2013. To estimate an LTBI prevalence of 10% with 95%
      CIs between 8% and 13%, we required 500 participants. RESULTS: 491/804 (61.1%)
      individuals agreed to be screened. The prevalence of LTBI was 16.5% (81/491; 95%
      CI 13.2 to 19.8). In UK-born individuals, a history of incarceration was
      associated with increased risk of LTBI (OR 3.49; 95% CI 1.10 to 11.04; P=0.018)
      after adjusting for age, length of time spent homeless and illicit drug use. Of
      the three subjects who met English treatment guidelines for LTBI at the time of
      the study, none engaged with services after referral for treatment. Prevalence of
      past hepatitis B infection was 10.4% (51/489; 95% CI 7.7 to 13.1), and 59.5%
      (291/489; 95% CI 55.1 to 63.9) of individuals were non-immune. Prevalence of
      current hepatitis C infection was 10.4% (51/489; 95% CI 7.8 to 13.1).
      CONCLUSIONS: This study demonstrates the high prevalence of LTBI in homeless
      people in London and the associated poor engagement with care. There is a large
      unmet need for LTBI and hepatitis C infection treatment, and hepatitis B
      vaccination, in this group.

PMID- 29378860
TI  - Dorsal Raphe Serotonin Neurons Mediate CO2-Induced Arousal from Sleep.
AB  - Arousal from sleep in response to CO2 is a critical protective phenomenon.
      Dysregulation of CO2-induced arousal contributes to morbidity and mortality from
      prevalent diseases, such as obstructive sleep apnea and sudden infant death
      syndrome. Despite the critical nature of this protective reflex, the precise
      mechanism for CO2-induced arousal is unknown. Because CO2 is a major regulator of
      breathing, prevailing theories suggest that activation of respiratory chemo- and
      mechano-sensors is required for CO2-induced arousal. However, populations of
      neurons that are not involved in the regulation of breathing are also
      chemosensitive. Among these are serotonin (5-HT) neurons in the dorsal raphe
      nucleus (DRN) that comprise a component of the ascending arousal system. We
      hypothesized that direct stimulation of these neurons with CO2 could cause
      arousal from sleep independently of enhancing breathing. Dialysis of CO2-rich
      acidified solution into DRN, but not medullary raphe responsible for modulating
      breathing, caused arousal from sleep. Arousal was lost in mice with a genetic
      absence of 5-HT neurons, and with acute pharmacological or optogenetic
      inactivation of DRN 5-HT neurons. Here we demonstrate that CO2 can cause arousal
      from sleep directly, without requiring enhancement of breathing, and that
      chemosensitive 5-HT neurons in the DRN critically mediate this arousal. Better
      understanding mechanisms underlying this protective reflex may lead to
      interventions to reduce disease-associated morbidity and mortality.SIGNIFICANCE
      STATEMENT Although CO2-induced arousal is critical to a number of diseases, the
      specific mechanism is not well understood. We previously demonstrated that
      serotonin (5-HT) neurons are important for CO2-induced arousal, as mice without 5
      HT neurons do not arouse to CO2 Many have interpreted this to mean that medullary
      5-HT neurons that regulate breathing are important in this arousal mechanism.
      Here we found that direct application of CO2-rich aCSF to the dorsal raphe
      nucleus, but not the medullary raphe, causes arousal from sleep, and that this
      arousal was lost with genetic ablation or acute inhibition of 5-HT neurons. We
      propose that 5-HT neurons in the dorsal raphe nucleus can be activated directly
      by CO2 to cause arousal independently of respiratory activation.

PMID- 29378861
TI  - Progranulin Gene Therapy Improves Lysosomal Dysfunction and Microglial Pathology
      Associated with Frontotemporal Dementia and Neuronal Ceroid Lipofuscinosis.
AB  - Loss-of-function mutations in progranulin, a lysosomal glycoprotein, cause
      neurodegenerative disease. Progranulin haploinsufficiency causes frontotemporal
      dementia (FTD) and complete progranulin deficiency causes CLN11 neuronal ceroid
      lipofuscinosis (NCL). Progranulin replacement is a rational therapeutic strategy
      for these disorders, but there are critical unresolved mechanistic questions
      about a progranulin gene therapy approach, including its potential to reverse
      existing pathology. Here, we address these issues using an AAV vector (AAV-Grn)
      to deliver progranulin in Grn-/- mice (both male and female), which model aspects
      of NCL and FTD pathology, developing lysosomal dysfunction, lipofuscinosis, and
      microgliosis. We first tested whether AAV-Grn could improve preexisting
      pathology. Even with treatment after onset of pathology, AAV-Grn reduced
      lipofuscinosis in several brain regions of Grn-/- mice. AAV-Grn also reduced
      microgliosis in brain regions distant from the injection site. AAV-expressed
      progranulin was only detected in neurons, not in microglia, indicating that the
      microglial activation in progranulin deficiency can be improved by targeting
      neurons and thus may be driven at least in part by neuronal dysfunction. Even
      areas with sparse transduction and almost undetectable progranulin showed
      improvement, indicating that low-level replacement may be sufficiently effective.
      The beneficial effects of AAV-Grn did not require progranulin binding to
      sortilin. Finally, we tested whether AAV-Grn improved lysosomal function. AAV
      derived progranulin was delivered to the lysosome, ameliorated the accumulation
      of LAMP-1 in Grn-/- mice, and corrected abnormal cathepsin D activity. These data
      shed light on progranulin biology and support progranulin-boosting therapies for
      NCL and FTD due to GRN mutations.SIGNIFICANCE STATEMENT Heterozygous loss-of
      function progranulin (GRN) mutations cause frontotemporal dementia (FTD) and
      homozygous mutations cause neuronal ceroid lipofuscinosis (NCL). Here, we address
      several mechanistic questions about the potential of progranulin gene therapy for
      these disorders. GRN mutation carriers with NCL or FTD exhibit lipofuscinosis and
      Grn-/- mouse models develop a similar pathology. AAV-mediated progranulin
      delivery reduced lipofuscinosis in Grn-/- mice even after the onset of pathology.
      AAV delivered progranulin only to neurons, not microglia, but improved
      microgliosis in several brain regions, indicating cross talk between neuronal and
      microglial pathology. Its beneficial effects were sortilin independent. AAV
      derived progranulin was delivered to lysosomes and corrected lysosomal
      abnormalities. These data provide in vivo support for the efficacy of progranulin
      boosting therapies for FTD and NCL.

PMID- 29378862
TI  - A Collaborator's Reputation Can Bias Decisions and Anxiety under Uncertainty.
AB  - Informational social influence theory posits that under conditions of
      uncertainty, we are inclined to look to others for advice. This leaves us
      remarkably vulnerable to being influenced by others' opinions or advice. Rational
      agents, however, do not blindly seek and act on arbitrary information, but often
      consider the quality of its source before committing to a course of action. Here,
      we ask the question of whether a collaborator's reputation can increase their
      social influence and, in turn, bias perception and anxiety under changing levels
      of uncertainty. Human male and female participants were asked to provide
      estimations of dot direction using the random dot motion (RDM) perceptual
      discrimination task and were paired with transient collaborators of high or low
      reputation whom provided their own estimations. The RDM varied in degrees of
      uncertainty and joint performance accuracy was linked to risk of an electric
      shock. Despite providing identical information, we show that collaborating with a
      high reputation compared with a low reputation partner, led to significantly more
      conformity during the RDM task for uncertain perceptual decisions. Consequently,
      high reputation partners decreased the subjects' anxiety during the anticipatory
      shock periods. fMRI data showed that parametric changes in conformity resulted in
      increased activity in the ventromedial PFC, whereas dissent was associated with
      increased in activity in the dorsal anterior cingulate cortex (dACC).
      Furthermore, the dACC and insula, regions involved in anticipatory pain, were
      significantly more active when collaborating with a low reputation partner. These
      results suggest that information about reputation can influence both cognitive
      and affective processes and in turn alter the neural circuits that underlie
      decision-making and emotion.SIGNIFICANCE STATEMENT Humans look to others for
      advice when making decisions under uncertainty. Rational agents, however, do not
      blindly seek information, but often consider the quality of its source before
      committing to a course of action. Here, we ask the question of whether a
      collaborators' reputation can increase social influence and in turn bias
      perception and anxiety in the context of perceptual uncertainty. We show that
      when subjects are partnered with collaborators with a high reputation, this leads
      to increased conformity during uncertain perceptual decision-making and reduces
      anxiety when joint performance accuracy leads to an electric shock. Furthermore,
      our results show that information about reputation alters the neural circuits
      that underlie decision-making and emotion.

PMID- 29378864
TI  - The Axon Initial Segment: An Updated Viewpoint.
AB  - At the base of axons sits a unique compartment called the axon initial segment
      (AIS). The AIS generates and shapes the action potential before it is propagated
      along the axon. Neuronal excitability thus depends crucially on the AIS
      composition and position, and these adapt to developmental and physiological
      conditions. The AIS also demarcates the boundary between the somatodendritic and
      axonal compartments. Recent studies have brought insights into the molecular
      architecture of the AIS and how it regulates protein trafficking. This Viewpoints
      article summarizes current knowledge about the AIS and highlights future
      challenges in understanding this key actor of neuronal physiology.

PMID- 29378863
TI  - Notch Suppression Collaborates with Ascl1 and Lin28 to Unleash a Regenerative
      Response in Fish Retina, But Not in Mice.
AB  - Muller glial (MG) cells in the zebrafish retina respond to injury by acquiring
      retinal stem-cell characteristics. Thousands of gene expression changes are
      associated with this event. Key among these changes is the induction of Ascl1a
      and Lin28a, two reprogramming factors whose expression is necessary for retina
      regeneration. Whether these factors are sufficient to drive MG proliferation and
      subsequent neuronal-fate specification remains unknown. To test this, we
      conditionally expressed Ascl1a and Lin28a in the uninjured retina of male and
      female fish. We found that together, their forced expression only stimulates
      sparse MG proliferation. However, in combination with Notch signaling inhibition,
      widespread MG proliferation and neuron regeneration ensued. Remarkably, Ascl1 and
      Lin28a expression in the retina of male and female mice also stimulated sparse MG
      proliferation, although this was not enhanced when combined with inhibitors of
      Notch signaling. Lineage tracing in both fish and mice suggested that the
      proliferating MG generated multipotent progenitors; however, this process was
      much more efficient in fish than mice. Overall, our studies suggest that the
      overexpression of Ascl1a and Lin28a in zebrafish, in combination with inhibition
      of Notch signaling, can phenocopy the effects of retinal injury in Muller glia.
      Interestingly, Ascl1 and Lin28a seem to have similar effects in fish and mice,
      whereas Notch signaling may differ. Understanding the different consequences of
      Notch signaling inhibition in fish and mice, may suggest additional strategies
      for enhancing retina regeneration in mammals.SIGNIFICANCE STATEMENT Mechanisms
      underlying retina regeneration in fish may suggest strategies for stimulating
      this process in mammals. Here we report that forced expression of Ascl1 and
      Lin28a can stimulate sparse MG proliferation in fish and mice; however, only in
      fish does Notch signaling inhibition collaborate with Ascl1a and Lin28a to
      stimulate widespread MG proliferation in the uninjured retina. Discerning
      differences in Notch signaling between fish and mice MG may reveal strategies for
      stimulating retina regeneration in mammals.

PMID- 29378866
TI  - Chronic stress alters adrenal clock function in a sexually dimorphic manner.
AB  - Glucocorticoid production is gated at the molecular level by the circadian clock
      in the adrenal gland. Stress influences daily rhythms in behavior and physiology,
      but it remains unclear how stress affects the function of the adrenal clock
      itself. Here, we examine the influence of stress on adrenal clock function by
      tracking PERIOD2::LUCIFERASE (PER2::LUC) rhythms in vitro Relative to non
      stressed controls, adrenals from stressed mice displayed marked changes in
      PER2::LUC rhythms. Interestingly, the effect of stress on adrenal rhythms varied
      by sex and the type of stress experienced in vivo To investigate the basis of sex
      differences in the adrenal response to stress, we next stimulated male and female
      adrenals in vitro with adrenocorticotropic hormone (ACTH). ACTH shifted phase and
      increased amplitude of adrenal PER2::LUC rhythms. Both phase and amplitude
      responses were larger in female adrenals than in male adrenals, an observation
      consistent with previously described sex differences in the physiological
      response to stress. Lastly, we reversed the sex difference in adrenal clock
      function using stress and sex hormone manipulations to test its role in driving
      adrenal responses to ACTH. We find that adrenal responsiveness to ACTH is
      inversely proportional to the amplitude of adrenal PER2::LUC rhythms. This
      suggests that larger ACTH responses from female adrenals may be driven by their
      lower amplitude molecular rhythms. Collectively, these results indicate a
      reciprocal relationship between stress and the adrenal clock, with stress
      influencing adrenal clock function and the state of the adrenal clock gating the
      response to stress in a sexually dimorphic manner.

PMID- 29378865
TI  - Saliency Detection as a Reactive Process: Unexpected Sensory Events Evoke
      Corticomuscular Coupling.
AB  - Survival in a fast-changing environment requires animals not only to detect
      unexpected sensory events, but also to react. In humans, these salient sensory
      events generate large electrocortical responses, which have been traditionally
      interpreted within the sensory domain. Here we describe a basic physiological
      mechanism coupling saliency-related cortical responses with motor output. In four
      experiments conducted on 70 healthy participants, we show that salient substartle
      sensory stimuli modulate isometric force exertion by human participants, and that
      this modulation is tightly coupled with electrocortical activity elicited by the
      same stimuli. We obtained four main results. First, the force modulation follows
      a complex triphasic pattern consisting of alternating decreases and increases of
      force, time-locked to stimulus onset. Second, this modulation occurs regardless
      of the sensory modality of the eliciting stimulus. Third, the magnitude of the
      force modulation is predicted by the amplitude of the electrocortical activity
      elicited by the same stimuli. Fourth, both neural and motor effects are not
      reflexive but depend on contextual factors. Together, these results indicate that
      sudden environmental stimuli have an immediate effect on motor processing,
      through a tight corticomuscular coupling. These observations suggest that
      saliency detection is not merely perceptive but reactive, preparing the animal
      for subsequent appropriate actions.SIGNIFICANCE STATEMENT Salient events
      occurring in the environment, regardless of their modalities, elicit large
      electrical brain responses, dominated by a widespread "vertex" negative-positive
      potential. This response is the largest synchronization of neural activity that
      can be recorded from a healthy human being. Current interpretations assume that
      this vertex potential reflects sensory processes. Contrary to this general
      assumption, we show that the vertex potential is strongly coupled with a
      modulation of muscular activity that follows the same pattern. Both the vertex
      potential and its motor effects are not reflexive but strongly depend on
      contextual factors. These results reconceptualize the significance of these
      evoked electrocortical responses, suggesting that saliency detection is not
      merely perceptive but reactive, preparing the animal for subsequent appropriate
      actions.

PMID- 29378867
TI  - IAPP and type 1 diabetes: implications for immunity, metabolism and islet
      transplants.
AB  - Islet amyloid polypeptide (IAPP), the main component of islet amyloid in type 2
      diabetes and islet transplants, is now recognized as a contributor to beta cell
      dysfunction. Increasingly, evidence warrants its investigation in type 1 diabetes
      owing to both its immunomodulatory and metabolic actions. Autoreactive T cells to
      IAPP-derived epitopes have been described in humans, suggesting that IAPP is an
      islet autoantigen in type 1 diabetes. In addition, although aggregates of IAPP
      have not been implicated in type 1 diabetes, they are potent pro-inflammatory
      stimuli to innate immune cells, and thus, could influence autoimmunity. IAPP
      aggregates also occur rapidly in transplanted islets and likely contribute to
      islet transplant failure in type 1 diabetes through sterile inflammation. In
      addition, since type 1 diabetes is a disease of both insulin and IAPP deficiency,
      clinical trials have examined the potential benefits of IAPP replacement in type
      1 diabetes with the injectable IAPP analogue, pramlintide. Pramlintide limits
      postprandial hyperglycemia by delaying gastric emptying and suppressing
      hyperglucagonemia, underlining the possible role of IAPP in postprandial glucose
      metabolism. Here, we review IAPP in the context of type 1 diabetes: from its
      potential involvement in type 1 diabetes pathogenesis, through its role in
      glucose metabolism and use of IAPP analogues as therapeutics, to its potential
      role in clinical islet transplant failure and considerations in this regard for
      future beta cell replacement strategies.

PMID- 29378868
TI  - Care for people with hepatitis C in provincial and territorial prisons.

PMID- 29378869
TI  - Intergenerational abortion tendency between mothers and teenage daughters: a
      population-based cohort study.
AB  - BACKGROUND: A teenage woman's sexual health practices may be influenced by her
      mother's experience. We evaluated whether there is an intergenerational tendency
      for induced abortion between mothers and their teenage daughters. METHODS: We
      conducted a retrospective population-based cohort study involving daughters born
      in Ontario between 1992 and 1999. We evaluated the daughters' data for induced
      abortions between age 12 years and their 20th birthday. We assessed each mother's
      history of induced abortion for the period from 4 years before her daughter's
      birth to 12 years after (i.e., when her daughter turned 12 years of age). We used
      Cox proportional hazard models to estimate a daughter's risk of having an induced
      abortion in relation to the mother's history of the same procedure. We adjusted
      hazard ratios (HRs) for maternal age and world region of origin, mental or
      physical health problems in the daughter, mother- daughter cohabitation,
      neighbourhood-level rate of teen induced abortion, rural or urban residence, and
      income quintile. RESULTS: A total of 431 623 daughters were included in the
      analysis. The cumulative probability of teen induced abortion was 10.1% (95%
      confidence interval [CI] 9.8%-10.4%) among daughters whose mother had an induced
      abortion, and 4.2% (95% CI 4.1%-4.3%) among daughters whose mother had no induced
      abortion, for an adjusted HR of 1.94 (95% CI 1.86-2.01). The adjusted HR of a
      teenaged daughter having an induced abortion in relation to number of maternal
      induced abortions was 1.77 (95% CI 1.69-1.85) with 1 maternal abortion, 2.04 (95%
      CI 1.91-2.18) with 2 maternal abortions, 2.39 (95% CI 2.19-2.62) with 3 maternal
      abortions and 2.54 (95% CI 2.33-2.77) with 4 or more maternal abortions, relative
      to none. INTERPRETATION: We found that the risk of teen induced abortion was
      higher among daughters whose mother had had an induced abortion. Future research
      should explore the mechanisms for intergenerational induced abortion.

PMID- 29378871
TI  - Dog bites.

PMID- 29378872
TI  - Eye complications from self-injury in a child.

PMID- 29378870
TI  - Diagnosis and management of congenital diaphragmatic hernia: a clinical practice
      guideline.

PMID- 29378873
TI  - What to do about the Canadian residency matching process?

PMID- 29378875
TI  - AI opens new frontier for suicide prevention.

PMID- 29378874
TI  - Unmatched Canadian medical graduates.

PMID- 29378876
TI  - Surgical fires: nightmarish "never events" persist.

PMID- 29378877
TI  - Disrespect within medicine for family doctors affects medical students and
      patients.

PMID- 29378878
TI  - Newborns exposed to opioids need mothers more than NICU, say pediatricians.

PMID- 29378879
TI  - The utility of transcriptomics in fish conservation.
AB  - There is growing recognition of the need to understand the mechanisms underlying
      organismal resilience (i.e. tolerance, acclimatization) to environmental change
      to support the conservation management of sensitive and economically important
      species. Here, we discuss how functional genomics can be used in conservation
      biology to provide a cellular-level understanding of organismal responses to
      environmental conditions. In particular, the integration of transcriptomics with
      physiological and ecological research is increasingly playing an important role
      in identifying functional physiological thresholds predictive of compensatory
      responses and detrimental outcomes, transforming the way we can study issues in
      conservation biology. Notably, with technological advances in RNA sequencing,
      transcriptome-wide approaches can now be applied to species where no prior
      genomic sequence information is available to develop species-specific tools and
      investigate sublethal impacts that can contribute to population declines over
      generations and undermine prospects for long-term conservation success. Here, we
      examine the use of transcriptomics as a means of determining organismal responses
      to environmental stressors and use key study examples of conservation concern in
      fishes to highlight the added value of transcriptome-wide data to the
      identification of functional response pathways. Finally, we discuss the gaps
      between the core science and policy frameworks and how thresholds identified
      through transcriptomic evaluations provide evidence that can be more readily used
      by resource managers.

PMID- 29378880
TI  - Flexibility of feeding movements in pigs: effects of changes in food toughness
      and stiffness on the timing of jaw movements.
AB  - In mammals, chewing movements can be modified, or flexible, in response to
      changes in food properties. Variability between and within food in the temporal
      characteristics of chewing movements can impact chewing frequency and
      rhythmicity, which in turn may affect food breakdown, energy expenditure and
      tooth wear. Here, we compared total chewing cycle duration and intra-cycle phase
      durations in pigs chewing on three foods varying in toughness and stiffness:
      apples (low toughness, low stiffness), carrots (high toughness, low stiffness),
      and almonds (high toughness, high stiffness). We also determined whether within
      food variability in timing parameters is modified in response to changes in food
      properties. X-ray Reconstruction Of Moving Morphology (XROMM) demonstrates that
      the timing of jaw movements are flexible in response to changes in food
      properties. Within each food, pigs also exhibited flexibility in their ability to
      vary cycle parameters. The timing of jaw movements during processing of high
      toughness foods is more variable, potentially decreasing chewing rhythmicity. In
      contrast, low-toughness foods result in jaw movements that are more stereotyped
      in their timing parameters. In addition, the duration of tooth-food-tooth contact
      is more variable during the processing of low-stiffness foods compared with tough
      or stiff foods. Increased toughness is suggested to alter the timing of the
      movements impacting food fracture whereas increased stiffness may require a more
      cautious control of jaw movements. This study emphasizes that flexibility in
      biological movements in response to changes in conditions may not only be
      observed in timing but also in the variability of their timing within each
      condition.

PMID- 29378881
TI  - Ammonia excretion in aquatic invertebrates: new insights and questions.
AB  - Invertebrates employ a variety of ammonia excretion strategies to facilitate
      their survival in diverse aquatic environments, including freshwater, seawater
      and the water film surrounding soil particles. Various environmental properties
      set innate challenges for an organism's ammonia excretory capacity. These include
      the availability of NaCl and the respective ion-permeability of the organism's
      transport epithelia, and the buffering capacity of their immediate surrounding
      medium. To this end, some transporters seem to be conserved in the excretory
      process. This includes the Na+/K+(NH4+)-ATPase (NKA), the NH3/CO2 dual gas
      channel Rhesus (Rh)-proteins and novel ammonia transporters (AMTs), which have
      been identified in several invertebrates but appear to be absent from
      vertebrates. In addition, recent evidence strongly suggests that the
      hyperpolarization-activated cyclic nucleotide-gated K+ channel (HCN) plays a
      significant role in ammonia excretion and is highly conserved throughout the
      animal kingdom. Furthermore, microtubule-dependent vesicular excretion pathways
      have been found in marine and soil-dwelling species, where, unlike freshwater
      systems, acid-trapping of excreted ammonia is difficult or absent owing to the
      high environmental buffering capacity of the surroundings. Finally, although
      ammonia is known to be a toxic nitrogenous waste product, certain marine species
      readily maintain potentially toxic hemolymph ammonia as a sort of ammonia
      homeostasis, which suggests that ammonia is involved in physiological processes
      and does not exist simply for excretion. Such findings are discussed within this
      Commentary and are hypothesized to be involved in acid-base regulation. We also
      describe excretory organs and processes that are dependent on environmental
      constraints and indicate gaps in the current knowledge in these topics.

PMID- 29378882
TI  - Bacteriophages of the Urinary Microbiome.
AB  - Bacterial viruses (bacteriophages) play a significant role in microbial community
      dynamics. Within the human gastrointestinal tract, for instance, associations
      among bacteriophages (phages), microbiota stability, and human health have been
      discovered. In contrast to the gastrointestinal tract, the phages associated with
      the urinary microbiota are largely unknown. Preliminary metagenomic surveys of
      the urinary virome indicate a rich diversity of novel lytic phage sequences at an
      abundance far outnumbering that of eukaryotic viruses. These surveys, however,
      exclude the lysogenic phages residing within the bacteria of the bladder. To
      characterize this phage population, we examined 181 genomes representative of the
      phylogenetic diversity of bacterial species within the female urinary microbiota
      and found 457 phage sequences, 226 of which were predicted with high confidence.
      Phages were prevalent within the bladder bacteria: 86% of the genomes examined
      contained at least one phage sequence. Most of these phages are novel, exhibiting
      no discernible sequence homology to sequences in public data repositories. The
      presence of phages with substantial sequence similarity within the microbiota of
      different women supports the existence of a core community of phages within the
      bladder. Furthermore, the observed variation between the phage populations of
      women with and without overactive bladder symptoms suggests that phages may
      contribute to urinary health. To complement our bioinformatic analyses, viable
      phages were cultivated from the bacterial isolates for characterization; a novel
      coliphage was isolated, which is obligately lytic in the laboratory strain
      Escherichia coli C. Sequencing of bacterial genomes facilitates a comprehensive
      cataloguing of the urinary virome and reveals phage-host interactions.IMPORTANCE
      Bacteriophages are abundant within the human body. However, while some niches
      have been well surveyed, the phage population within the urinary microbiome is
      largely unknown. Our study is the first survey of the lysogenic phage population
      within the urinary microbiota. Most notably, the abundance of prophage exceeds
      that of the bacteria. Furthermore, many of the prophage sequences identified
      exhibited no recognizable sequence homology to sequences in data repositories.
      This suggests a rich diversity of uncharacterized phage species present in the
      bladder. Additionally, we observed a variation in the abundances of phages
      between bacteria isolated from asymptomatic "healthy" individuals and those with
      urinary symptoms, thus suggesting that, like phages within the gut, phages within
      the bladder may contribute to urinary health.

PMID- 29378883
TI  - Endopeptidase PepO Regulates the SpeB Cysteine Protease and Is Essential for the
      Virulence of Invasive M1T1 Streptococcus pyogenes.
AB  - Streptococcus pyogenes (group A Streptococcus [GAS]) causes a wide range of human
      infections. The pathogenesis of GAS infections is dependent on the temporal
      expression of numerous secreted and surface-associated virulence factors that
      interact with host proteins. Streptococcal pyrogenic exotoxin B (SpeB) is one of
      the most extensively studied toxins produced by GAS, and the coordinate growth
      phase-dependent regulation of speB expression is linked to disease severity
      phenotypes. Here, we identified the endopeptidase PepO as a novel growth phase
      dependent regulator of SpeB in the invasive GAS M1 serotype strain 5448. By using
      transcriptomics followed by quantitative reverse transcriptase PCR and Western
      blot analyses, we demonstrate through targeted mutagenesis that PepO influences
      growth phase-dependent induction of speB gene expression. Compared to wild-type
      and complemented mutant strains, we demonstrate that the 5448DeltapepO mutant
      strain is more susceptible to killing by human neutrophils and is attenuated in
      virulence in a murine model of invasive GAS infection. Our results expand the
      complex regulatory network that is operating in GAS to control SpeB production
      and suggest that PepO is a virulence requirement during GAS M1T1 strain 5448
      infections.IMPORTANCE Despite the continuing susceptibility of S. pyogenes to
      penicillin, this bacterial pathogen remains a leading infectious cause of global
      morbidity and mortality. A particular subclone of the M1 serotype (M1T1) has
      persisted globally for decades as the most frequently isolated serotype from
      patients with invasive and noninvasive diseases in Western countries. One of the
      key GAS pathogenicity factors is the potent broad-spectrum cysteine protease
      SpeB. Although there has been extensive research interest on the regulatory
      mechanisms that control speB gene expression, its genetic regulation is not fully
      understood. Here, we identify the endopeptidase PepO as a new regulator of speB
      gene expression in the globally disseminated M1T1 clone and as being essential
      for virulence.

PMID- 29378885
TI  - Selective Utilization of Benzimidazolyl-Norcobamides as Cofactors by the
      Tetrachloroethene Reductive Dehalogenase of Sulfurospirillum multivorans.
AB  - The organohalide-respiring bacterium Sulfurospirillum multivorans produces a
      unique cobamide, namely, norpseudo-B12, which serves as cofactor of the
      tetrachloroethene (PCE) reductive dehalogenase (PceA). As previously reported, a
      replacement of the adeninyl moiety, the lower base of the cofactor, by
      exogenously applied 5,6-dimethylbenzimidazole led to inactive PceA. To explore
      the general effect of benzimidazoles on the PCE metabolism, the susceptibility of
      the organism for guided biosynthesis of various singly substituted benzimidazolyl
      norcobamides was investigated, and their use as cofactor by PceA was analyzed.
      Exogenously applied 5-methylbenzimidazole (5-MeBza), 5-hydroxybenzimidazole (5
      OHBza), and 5-methoxybenzimidazole (5-OMeBza) were found to be efficiently
      incorporated as lower bases into norcobamides (NCbas). Structural analysis of the
      NCbas by nuclear magnetic resonance spectroscopy uncovered a regioselectivity in
      the utilization of these precursors for NCba biosynthesis. When 5-MeBza was
      added, a mixture of 5-MeBza-norcobamide and 6-MeBza-norcobamide was formed, and
      the PceA enzyme activity was affected. In the presence of 5-OHBza, almost
      exclusively 6-OHBza-norcobamide was produced, while in the presence of 5-OMeBza,
      predominantly 5-OMeBza-norcobamide was detected. Both NCbas were incorporated
      into PceA, and no negative effect on the PceA activity was observed. In crystal
      structures of PceA, both NCbas were bound in the base-off mode with the 6-OHBza
      and 5-OMeBza lower bases accommodated by the same solvent-exposed hydrophilic
      pocket that harbors the adenine as the lower base of authentic norpseudo-B12 In
      this study, a selective production of different norcobamide isomers containing
      singly substituted benzimidazoles as lower bases is shown, and unique structural
      insights into their utilization as cofactors by a cobamide-containing enzyme are
      provided.IMPORTANCE Guided biosynthesis of norcobamides containing singly
      substituted benzimidazoles as lower bases by the organohalide-respiring
      epsilonproteobacterium Sulfurospirillum multivorans is reported. An unprecedented
      specificity in the formation of norcobamide isomers containing hydroxylated or
      methoxylated benzimidazoles was observed that implicated a strict
      regioselectivity of the norcobamide biosynthesis in the organism. In contrast to
      5,6-dimethylbenzimidazolyl-norcobamide, the incorporation of singly substituted
      benzimidazolyl-norcobamides as a cofactor into the tetrachloroethene reductive
      dehalogenase was not impaired. The enzyme was found to be functional with
      different isomers and not limited to the use of adeninyl-norcobamide. Structural
      analysis of the enzyme equipped with either adeninyl- or benzimidazolyl
      norcobamide cofactors visualized for the first time structurally different
      cobamides bound in base-off conformation to the cofactor-binding site of a
      cobamide-containing enzyme.

PMID- 29378884
TI  - Distinct Regulatory Role of Carbon Catabolite Protein A (CcpA) in Oral
      Streptococcal spxB Expression.
AB  - Pyruvate oxidase (SpxB)-dependent H2O2 production is under the control of carbon
      catabolite protein A (CcpA) in the oral species Streptococcus sanguinis and
      Streptococcus gordonii Interestingly, both species react differently to the
      presence of the preferred carbohydrate source glucose. S. gordonii CcpA-dependent
      regulation of spxB follows classical carbon catabolite repression. Conversely,
      spxB expression in S. sanguinis is not influenced by glucose but is repressed by
      CcpA. Here, we constructed strains expressing the heterologous versions of CcpA
      or the spxB promoter region to learn if the distinct regulation of spxB
      expression is transferable from S. gordonii to S. sanguinis and vice versa. While
      cross-species binding of CcpA to the spxB promoter is conserved in vitro, we were
      unable to swap the species-specific regulation. This suggests that a regulatory
      mechanism upstream of CcpA most likely is responsible for the observed difference
      in spxB expression. Moreover, the overall ecological significance of differential
      spxB regulation in the presence of various glucose concentrations was tested with
      additional oral streptococcus isolates and demonstrated that carbohydrate
      dependent and carbohydrate-independent mechanisms exist to control expression of
      spxB in the oral biofilm. Overall, our data demonstrate the unexpected finding
      that metabolic pathways between two closely related oral streptococcal species
      can be regulated differently despite an exceptionally high DNA sequence
      identity.IMPORTANCE Polymicrobial diseases are the result of interactions among
      the residential microbes, which can lead to a dysbiotic community. Streptococcus
      sanguinis and Streptococcus gordonii are considered commensal species that are
      present in the healthy dental biofilm. Both species are able to produce
      significant amounts of H2O2 via the enzymatic action of the pyruvate oxidase
      SpxB. H2O2 is able to inhibit species associated with oral diseases. SpxB and its
      gene-regulatory elements present in both species are highly conserved.
      Nonetheless, a differential response to the presence of glucose was observed.
      Here, we investigate the mechanisms that lead to this differential response.
      Detailed knowledge of the regulatory mechanisms will aid in a better
      understanding of oral disease development and how to prevent dysbiosis.

PMID- 29378886
TI  - HilE Regulates HilD by Blocking DNA Binding in Salmonella enterica Serovar
      Typhimurium.
AB  - The Salmonella type three secretion system (T3SS), encoded in the Salmonella
      pathogenicity island 1 (SPI1) locus, mediates the invasion of the host intestinal
      epithelium. SPI1 expression is dependent upon three AraC-like regulators: HilD,
      HilC, and RtsA. These regulators act in a complex feed-forward loop to activate
      each other and hilA, which encodes the activator of the T3SS structural genes.
      HilD has been shown to be the major integration point of most signals known to
      activate the expression of the SPI1 T3SS, acting as a switch to control induction
      of the system. HilE is a negative regulator that acts upon HilD. Here we provide
      genetic and biochemical data showing that HilE specifically binds to HilD but not
      to HilC or RtsA. This protein-protein interaction blocks the ability of HilD to
      bind DNA as shown by both an in vivo reporter system and an in vitro gel shift
      assay. HilE does not affect HilD dimerization, nor does it control the stability
      of the HilD protein. We also investigated the role of HilE during the infection
      of mice using competition assays. Although deletion of hilE does not confer a
      phenotype, the hilE mutation does suppress the invasion defect conferred by loss
      of FliZ, which acts as a positive signal controlling HilD protein activity.
      Together, these data suggest that HilE functions to restrict low-level HilD
      activity, preventing premature activation of SPI1 until positive inputs reach a
      threshold required to fully induce the system.IMPORTANCESalmonella is a leading
      cause of gastrointestinal and systemic disease throughout the world. The SPI1
      T3SS is required for Salmonella to induce inflammatory diarrhea and to gain
      access to underlying tissue. A complex regulatory network controls expression of
      SPI1 in response to numerous physiological inputs. Most of these signals impinge
      primarily on HilD translation or activity. The system is triggered when HilD
      activity crosses a threshold that allows efficient activation of its own
      promoter. This threshold is set by HilE, which binds to HilD to prevent the
      inevitable minor fluctuations in HilD activity from inappropriately activating
      the system. The circuit also serves as a paradigm for systems that must integrate
      numerous environmental parameters to control regulatory output.

PMID- 29378888
TI  - Shining the Light on Cyclic di-GMP Dark Matter.
AB  - Bacterial cyclic di-GMP signaling networks often consist of dozens of components,
      and the majority of these components have no observable function. Dahlstrom et
      al. (J. Bacteriol. 200:e00703-17, 2018, https://doi.org/10.1128/JB.00703-17)
      explored the function of every component of the Pseudomonas fluorescens cyclic di
      GMP network under 188 different growth conditions and identified activities for
      80% of the network. They further demonstrated that multiple mechanisms function
      in tandem to control the activity of the network in different environments.

PMID- 29378887
TI  - Survival of Anaerobic Fe2+ Stress Requires the ClpXP Protease.
AB  - Shewanella oneidensis strain MR-1 is a versatile bacterium capable of respiring
      extracellular, insoluble ferric oxide minerals under anaerobic conditions. The
      respiration of iron minerals results in the production of soluble ferrous ions,
      which at high concentrations are toxic to living organisms. It is not fully
      understood how Fe2+ is toxic to cells anaerobically, nor is it fully understood
      how S. oneidensis is able to resist high levels of Fe2+ Here we describe the
      results of a transposon mutant screen and subsequent deletion of the genes clpX
      and clpP in S. oneidensis, which demonstrate that the protease ClpXP is required
      for anaerobic Fe2+ resistance. Many cellular processes are known to be regulated
      by ClpXP, including entry into stationary phase, envelope stress response, and
      turnover of stalled ribosomes. However, none of these processes appears to be
      responsible for mediating anaerobic Fe2+ resistance in S. oneidensis Protein
      trapping studies were performed to identify ClpXP targets in S. oneidensis under
      Fe2+ stress, implicating a wide variety of protein targets. Escherichia coli
      strains lacking clpX or clpP also display increased sensitivity to Fe2+
      anaerobically, indicating Fe2+ resistance may be a conserved role for the ClpXP
      protease system. Hypotheses regarding the potential role(s) of ClpXP during
      periods of high Fe2+ are discussed. We speculate that metal-containing proteins
      are misfolded under conditions of high Fe2+ and that the ClpXP protease system is
      necessary for their turnover.IMPORTANCE Prior to the evolution of cyanobacteria
      and oxygenic photosynthesis, life arose and flourished in iron-rich oceans.
      Today, aqueous iron-rich environments are less common, constrained to low-pH
      conditions and anaerobic systems such as stratified lakes and seas, digestive
      tracts, subsurface environments, and sediments. The latter two ecosystems often
      favor dissimilatory metal reduction, a process that produces soluble Fe2+ from
      iron oxide minerals. Dissimilatory metal-reducing bacteria must therefore have
      mechanisms to tolerate anaerobic Fe2+ stress, and studying resistance in these
      organisms may help elucidate the basis of toxicity. Shewanella oneidensis is a
      model dissimilatory metal-reducing bacterium isolated from metal-rich sediments.
      Here we demonstrate a role for ClpXP, a protease system widely conserved in
      bacteria, in anaerobic Fe2+ resistance in both S. oneidensis and Escherichia
      coli.

PMID- 29378889
TI  - PhoPR Positively Regulates whiB3 Expression in Response to Low pH in Pathogenic
      Mycobacteria.
AB  - During infection, Mycobacterium tuberculosis colonizes macrophages or necrotic
      granulomas, in which low pH is one of the major challenges. The PhoPR two
      component regulatory system and the cytosolic redox sensor WhiB3 both play
      important roles in the response to low pH by M. tuberculosis However, whether
      close association exists between PhoPR and WhiB3 remains unclear. In this study,
      the positive regulation of whiB3 by PhoPR in mycobacteria was characterized. We
      observed that the expression patterns of the whiB3 gene under acidic conditions
      are different among mycobacterial species, suggesting that the regulation of
      whiB3 differs among mycobacteria. A sequence analysis of the whiB3 promoters
      (whiB3p) from M. tuberculosis and two closely related species, namely, M. marinum
      and M. smegmatis, showed that the whiB3p regions from M. tuberculosis and M.
      marinum contain a new type of PhoP box that is absent in the M. smegmatiswhiB3p
      Direct binding of PhoP to whiB3p from M. tuberculosis and M. marinum but not that
      from M. smegmatis was validated by in vitro protein-DNA binding assays. The
      direct activation of whiB3 by PhoPR under acidic conditions was further verified
      by reverse transcription-quantitative PCR (qRT-PCR) analysis in M. marinum
      Moreover, mutating the residues important for the phosphorylation pathway of
      PhoPR in M. marinum abolished the activation of whiB3 expression by PhoPR under
      acidic conditions, suggesting that low pH triggers the phosphorylation of PhoPR,
      which in turn activates the transcription of whiB3 Since the PhoP box was only
      identified in whiB3p of pathogenic mycobacteria, we suggest that the PhoPR-whiB3
      regulatory pathway may have evolved to facilitate mycobacterial
      infection.IMPORTANCE The low pH in macrophages is an important barrier for
      infection by microbes. The PhoPR two-component regulatory system is required for
      the response to low pH and plays a role in redox homeostasis in Mycobacterium
      tuberculosis WhiB3, a cytosolic redox-sensing transcriptional regulator, is also
      involved in these processes. However, there is no direct evidence to demonstrate
      the regulation of WhiB3 by PhoPR. In this study, we found that PhoPR directly
      activates whiB3 expression in response to low pH. An atypical PhoP box in the
      whiB3 promoters has been identified and is only found in pathogenic mycobacteria,
      which suggests that the PhoPR-whiB3 regulatory pathway may facilitate
      mycobacterial infection. This study provides novel information for further
      characterization of the PhoPR regulon.

PMID- 29378890
TI  - The Conserved DNA Binding Protein WhiA Influences Chromosome Segregation in
      Bacillus subtilis.
AB  - The DNA binding protein WhiA is conserved in Gram-positive bacteria and is
      present in the genetically simple cell wall-lacking mycoplasmas. The protein
      shows homology to eukaryotic homing endonucleases but lacks nuclease activity.
      WhiA was first characterized in streptomycetes, where it regulates the expression
      of key differentiation genes, including the cell division gene ftsZ, which is
      essential for sporulation. For Bacillus subtilis, it was shown that WhiA is
      essential when certain cell division genes are deleted. However, in B. subtilis,
      WhiA is not required for sporulation, and it does not seem to function as a
      transcription factor, despite its DNA binding activity. The exact function of B.
      subtilis WhiA remains elusive. We noticed that whiA mutants show an increased
      space between their nucleoids, and here, we describe the results of fluorescence
      microscopy, genetic, and transcriptional experiments to further investigate this
      phenomenon. It appeared that the deletion of whiA is synthetic lethal when either
      the DNA replication and segregation regulator ParB or the DNA replication
      inhibitor YabA is absent. However, WhiA does not seem to affect replication
      initiation. We found that a DeltawhiA mutant is highly sensitive for DNA-damaging
      agents. Further tests revealed that the deletion of parAB induces the SOS
      response, including the cell division inhibitor YneA. When yneA was inactivated,
      the viability of the synthetic lethal DeltawhiA DeltaparAB mutant was restored.
      However, the nucleoid segregation phenotype remained. These findings underline
      the importance of WhiA for cell division and indicate that the protein also plays
      a role in DNA segregation.IMPORTANCE The conserved WhiA protein family can be
      found in most Gram-positive bacteria, including the genetically simple cell wall
      lacking mycoplasmas, and these proteins play a role in cell division. WhiA has
      some homology with eukaryotic homing endonucleases but lacks nuclease activity.
      Because of its DNA binding activity, it is assumed that the protein functions as
      a transcription factor, but this is not the case in the model system B. subtilis
      The function of this protein in B. subtilis remains unclear. We noticed that a
      whiA mutant has a mild chromosome segregation defect. Further studies of this
      phenomenon provided new support for a functional role of WhiA in cell division
      and indicated that the protein is required for normal chromosome segregation.

PMID- 29378891
TI  - Nutritional Regulation of the Sae Two-Component System by CodY in Staphylococcus
      aureus.
AB  - Staphylococcus aureus subverts innate defenses during infection in part by
      killing host immune cells to exacerbate disease. This human pathogen intercepts
      host cues and activates a transcriptional response via the S. aureus exoprotein
      expression (SaeR/SaeS [SaeR/S]) two-component system to secrete virulence factors
      critical for pathogenesis. We recently showed that the transcriptional repressor
      CodY adjusts nuclease (nuc) gene expression via SaeR/S, but the mechanism
      remained unknown. Here, we identified two CodY binding motifs upstream of the sae
      P1 promoter, which suggested direct regulation by this global regulator. We show
      that CodY shares a binding site with the positive activator SaeR and that
      alleviating direct CodY repression at this site is sufficient to abrogate
      stochastic expression, suggesting that CodY represses sae expression by blocking
      SaeR binding. Epistasis experiments support a model that CodY also controls sae
      indirectly through Agr and Rot-mediated repression of the sae P1 promoter. We
      also demonstrate that CodY repression of sae restrains production of secreted
      cytotoxins that kill human neutrophils. We conclude that CodY plays a previously
      unrecognized role in controlling virulence gene expression via SaeR/S and suggest
      a mechanism by which CodY acts as a master regulator of pathogenesis by tying
      nutrient availability to virulence gene expression.IMPORTANCE Bacterial
      mechanisms that mediate the switch from a commensal to pathogenic lifestyle are
      among the biggest unanswered questions in infectious disease research. Since the
      expression of most virulence genes is often correlated with nutrient depletion,
      this implies that virulence is a response to the lack of nourishment in host
      tissues and that pathogens like S. aureus produce virulence factors in order to
      gain access to nutrients in the host. Here, we show that specific nutrient
      depletion signals appear to be funneled to the SaeR/S system through the global
      regulator CodY. Our findings reveal a strategy by which S. aureus delays the
      production of immune evasion and immune-cell-killing proteins until key nutrients
      are depleted.

PMID- 29378892
TI  - CpxR-Dependent Thermoregulation of Serratia marcescens PrtA Metalloprotease
      Expression and Its Contribution to Bacterial Biofilm Formation.
AB  - PrtA is the major secreted metalloprotease of Serratia marcescens Previous
      reports implicate PrtA in the pathogenic capacity of this bacterium. PrtA is also
      clinically used as a potent analgesic and anti-inflammatory drug, and its
      catalytic properties attract industrial interest. Comparatively, there is scarce
      knowledge about the mechanisms that physiologically govern PrtA expression in
      Serratia In this work, we demonstrate that PrtA production is derepressed when
      the bacterial growth temperature decreases from 37 degrees C to 30 degrees C. We
      show that this thermoregulation occurs at the transcriptional level. We
      determined that upstream of prtA, there is a conserved motif that is directly
      recognized by the CpxR transcriptional regulator. This feature is found along
      Serratia strains irrespective of their isolation source, suggesting an
      evolutionary conservation of CpxR-dependent regulation of PrtA expression. We
      found that in S. marcescens, the CpxAR system is more active at 37 degrees C than
      at 30 degrees C. In good agreement with these results, in a cpxR mutant
      background, prtA is derepressed at 37 degrees C, while overexpression of the NlpE
      lipoprotein, a well-known CpxAR-inducing condition, inhibits PrtA expression,
      suggesting that the levels of the activated form of CpxR are increased at 37
      degrees C over those at 30 degrees C. In addition, we establish that PrtA is
      involved in the ability of S. marcescens to develop biofilm. In accordance, CpxR
      influences the biofilm phenotype only when bacteria are grown at 37 degrees C. In
      sum, our findings shed light on regulatory mechanisms that fine-tune PrtA
      expression and reveal a novel role for PrtA in the lifestyle of S.
      marcescensIMPORTANCE We demonstrate that S. marcescens metalloprotease PrtA
      expression is transcriptionally thermoregulated. While strongly activated below
      30 degrees C, its expression is downregulated at 37 degrees C. We found that in
      S. marcescens, the CpxAR signal transduction system, which responds to envelope
      stress and bacterial surface adhesion, is activated at 37 degrees C and able to
      downregulate PrtA expression by direct interaction of CpxR with a binding motif
      located upstream of the prtA gene. Moreover, we reveal that PrtA expression
      favors the ability of S. marcescens to develop biofilm, irrespective of the
      bacterial growth temperature. In this context, thermoregulation along with a
      highly conserved CpxR-dependent modulation mechanism gives clues about the
      relevance of PrtA as a factor implicated in the persistence of S. marcescens on
      abiotic surfaces and in bacterial host colonization capacity.

PMID- 29378893
TI  - Regulation of the CRISPR-associated genes by Rv2837c (CnpB) via an Orn-like
      activity in TB complex mycobacteria.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR
      associated proteins (Cas) provide an adaptive immunity to bacteria and archaea
      against specific DNA invaders. Mycobacterium tuberculosis (Mtb) encodes a Type
      III CRISPR-Cas system, which has not been experimentally explored. In this study,
      we found that the CRISPR-Cas systems of both Mtb and M. bovis BCG were highly
      upregulated by deletion of Rv2837c (cnpB), which encodes a multifunctional
      protein that hydrolyzes cyclic di-AMP (c-di-AMP), cyclic di-GMP (c-di-GMP), and
      nanoRNAs (short oligonucleotides of five residues or shorter in length). By using
      genetic and biochemical approaches, we demonstrated that the CnpB-controlled
      transcriptional regulation of the CRISPR-Cas system is mediated by an Orn-like
      activity, rather than hydrolyzing the cyclic di-nucleotides. Additionally, our
      results revealed that tuberculosis (TB) complex mycobacteria are functional in
      processing CRISPR RNAs (crRNAs), which are also more abundant in DeltacnpB
      compared to the parent strain. The elevated crRNA levels in DeltacnpB can be
      partially reduced by expressing E. coli orn Our findings provide new insight into
      transcriptional regulation of bacterial CRISPR-Cas systems.Importance Clustered
      regularly interspaced short palindromic repeats (CRISPR) and the CRISPR
      associated proteins (Cas) provide an adaptive immunity against specific DNA
      invaders. Mycobacterium tuberculosis (Mtb) encodes a Type III CRISPR-Cas system,
      which has not been experimentally explored. In this study, we first demonstrated
      that the CRISPR-Cas systems in tuberculosis (TB) complex mycobacteria are
      functional in processing CRISPR RNAs (crRNAs). We also showed that Rv2837c (CnpB)
      controls the expression of the CRISPR-Cas systems in TB complex mycobacteria
      through an oligoribonuclease (Orn)-like activity, which is very likely mediated
      by nanoRNA. Since little is known about regulation of CRISPR-Cas systems, our
      findings provide new insight into transcriptional regulation of bacterial CRISPR
      Cas systems.

PMID- 29378895
TI  - Correction for Takano et al., "Vital Role of the Calpain-Calpastatin System for
      Placental-Integrity-Dependent Embryonic Survival".

PMID- 29378894
TI  - Characterization of a Unique Outer Membrane Protein Required for Oxidative Stress
      Resistance and Virulence of Francisella tularensis.
AB  - Francisella tularensis, the causative agent of tularemia, lacks typical bacterial
      virulence factors and toxins but still exhibits extreme virulence. The bacterial
      multidrug efflux systems consist of an inner membrane, a transmembrane membrane
      fusion protein, and an outer membrane (OM) component that form a contiguous
      channel for the secretion of a multitude of bacterial products. Francisella
      contains three orthologs of the OM proteins; two of these, termed TolC and FtlC,
      are important for tularemia pathogenesis. The third OM protein, SilC, is
      homologous to the silver cation efflux protein of other bacterial pathogens. The
      silC gene (FTL_0686) is located on an operon encoding an Emr-type multidrug
      efflux pump of F. tularensis The role of SilC in tularemia pathogenesis is not
      known. In this study, we investigated the role of SilC in secretion and virulence
      of F. tularensis by generating a silC gene deletion (DeltasilC) mutant and its
      transcomplemented strain. Our results demonstrate that the DeltasilC mutant
      exhibits increased sensitivity to antibiotics, oxidants, silver, diminished
      intramacrophage growth, and attenuated virulence in mice compared to wild-type F.
      tularensis However, the secretion of antioxidant enzymes of F. tularensis is not
      impaired in the DeltasilC mutant. The virulence of the DeltasilC mutant is
      restored in NADPH oxidase-deficient mice, indicating that SilC resists oxidative
      stress in vivo Collectively, this study demonstrates that the OM component SilC
      serves a specialized role in virulence of F. tularensis by conferring resistance
      against oxidative stress and silver.IMPORTANCEFrancisella tularensis, the
      causative agent of a fatal human disease known as tularemia, is a category A
      select agent and a potential bioterror agent. The virulence mechanisms of
      Francisella are not completely understood. This study investigated the role of a
      unique outer membrane protein, SilC, of a multidrug efflux pump in the virulence
      of F. tularensis This is the first report demonstrating that the OM component
      SilC plays an important role in efflux of silver and contributes to the virulence
      of F. tularensis primarily by providing resistance against oxidative stress.
      Characterization of these unique virulence mechanisms will provide an
      understanding of the pathogenesis of tularemia and identification of potential
      targets for the development of effective therapeutics and prophylactics for
      protection from this lethal disease.

PMID- 29378897
TI  - Screening Children at Risk for Retinoblastoma.

PMID- 29378896
TI  - Erratum for Liu et al., "Increasing the Unneddylated Cullin1 Portion Rescues the
      csn Phenotypes by Stabilizing Adaptor Modules To Drive SCF Assembly".

PMID- 29378899
TI  - Injury and Mortality Among Children Identified as at High Risk of Maltreatment.
AB  - OBJECTIVES: To determine if children identified by a predictive risk model as at
      "high risk" of maltreatment are also at elevated risk of injury and mortality in
      early childhood. METHODS: We built a model that predicted a child's risk of a
      substantiated finding of maltreatment by child protective services for children
      born in New Zealand in 2010. We assigned risk scores to the 2011 birth cohort,
      and flagged children as "very high risk" if they were in the top 10% of the score
      distribution for maltreatment. We also set a less conservative threshold for
      defining "high risk" and examined children in the top 20%. We then compared the
      incidence of injury and mortality rates between very high-risk and high-risk
      children and the remainder of the birth cohort. RESULTS: Children flagged at both
      10% and 20% risk thresholds had much higher postneonatal mortality rates than
      other children (4.8 times and 4.2 times greater, respectively), as well as a
      greater relative risk of hospitalization (2 times higher and 1.8 times higher,
      respectively). CONCLUSIONS: Models that predict risk of maltreatment as defined
      by child protective services substantiation also identify children who are at
      heightened risk of injury and mortality outcomes. If deployed at birth, these
      models could help medical providers identify children in families who would
      benefit from more intensive supports.

PMID- 29378900
TI  - If We Had a Crystal Ball, Would We Use It?

PMID- 29378901
TI  - Gut as an emerging organ for the treatment of diabetes: focus on mechanism of
      action of bariatric and endoscopic interventions.
AB  - Increasing worldwide prevalence of type 2 diabetes mellitus and its accompanying
      pathologies such as obesity, arterial hypertension and dyslipidemia represents
      one of the most important challenges of current medicine. Despite intensive
      efforts, high percentage of patients with type 2 diabetes does not achieve
      treatment goals and struggle with increasing body weight and poor glucose
      control. While novel classes of antidiabetic medications such as incretin-based
      therapies and gliflozins have some favorable characteristics compared to older
      antidiabetics, the only therapeutic option shown to substantially modify the
      progression of diabetes or to achieve its remission is bariatric surgery. Its
      efficacy in the treatment of diabetes is well established, but the exact
      underlying modes of action are still only partially described. They include
      restriction of food amount, enhanced passage of chymus into distal part of small
      intestine with subsequent modification of gastrointestinal hormones and bile
      acids secretion, neural mechanisms, changes in gut microbiota and many other
      possible mechanisms underscoring the importance of the gut in the regulation of
      glucose metabolism. In addition to bariatric surgery, less-invasive endoscopic
      methods based on the principles of bariatric surgery were introduced and showed
      promising results. This review highlights the role of the intestine in the
      regulation of glucose homeostasis focusing on the mechanisms of action of
      bariatric and especially endoscopic methods of the treatment of diabetes. A
      better understanding of these mechanisms may lead to less invasive endoscopic
      treatments of diabetes and obesity that may complement and widen current
      therapeutic options.

PMID- 29378903
TI  - Factors associated with partner notification of STIs in men who have sex with men
      on PrEP in France: a cross-sectional substudy of the ANRS-IPERGAY trial.
AB  - OBJECTIVES: Partner notification (PN) is a useful public health approach to
      enhance targeted testing of people at high risk of HIV and other STIs, and
      subsequent linkage to care for those diagnosed. In France, no specific PN
      guidelines exist and information about current practices is scarce. We used the
      ANRS-IPERGAY PrEP trial to investigate PN in HIV-negative men who have sex with
      men (MSM) reporting a bacterial STI. METHODS: This substudy included 275
      participants who completed a specific online PN questionnaire during the open
      label extension study of the ANRS-Intervention Preventive de l'Exposition aux
      Risques avec et pour les Gays (IPERGAY) trial. Variables used as proxies of at
      risk practices were defined using data collected at the previous follow-up visit
      about participants' most recent sexual encounter and preventive behaviours. chi2
      or Fisher's exact test helped select variables eligible for multiple logistic
      models. RESULTS: Of the 275 participants, 250 reported at least one previous STI.
      Among the latter, 172 (68.8%) had informed their partner(s) of their most recent
      STI. Of these, 138 (80.2%) and 83 (48.3%) had notified their casual and main
      partners, respectively. Participants were less likely to notify their main
      partner when their most recent sexual encounter involved unsafe anal sex with a
      casual partner (adjusted OR (aOR) (95% CI) 0.18 (0.06 to 0.54), P=0.02). Older
      participants were less likely to inform casual partners (aOR (95% CI) 0.44 (0.21
      to 0.94), P=0.03), while those practising chemsex during their most recent sexual
      encounter were more likely to inform their casual partners (aOR (95% CI) 2.56
      (1.07 to 6.09), P=0.03). CONCLUSION: Unsafe sexual encounters with people other
      than main partners and street drugs use were two sociobehavioural factors
      identified, respectively, as a barrier to main PN and a motivator for casual PN,
      in a sample of high-risk MSM. These results provide an insight into current PN
      practices regarding STI in France and might inform future decisions about how to
      define feasible and acceptable PN programmes.

PMID- 29378902
TI  - Asymptomatic lymphogranuloma venereum among Nigerian men who have sex with men.
AB  - OBJECTIVES: Recent outbreaks of anorectal lymphogranuloma venereum (LGV) among
      men who have sex with men (MSM) have been characterised by proctocolitis
      requiring extended antibiotic treatment compared with infections caused by other
      serovars of Chlamydia trachomatis (CT). We describe the prevalence and clinical
      features of LGV among Nigerian MSM diagnosed with anorectal CT. METHODS: MSM were
      recruited for this observational cohort in Lagos, Nigeria, using respondent
      driven sampling and screened for HIV and bacterial STIs every three months for up
      to 18 months. Nucleic acid amplification tests for CT were performed on rectal
      swab specimens. Prevalent and incident cases of anorectal CT underwent additional
      testing to identify LGV using novel real-time PCR assays specific for the L
      serovars of CT. RESULTS: From April 2014 to July 2016, 420 MSM underwent testing
      for rectal STIs, of whom 66 (15.7%) had prevalent anorectal CT. Among those
      without prevalent disease, 68 developed incident infections during 208 person
      years of follow-up. Of 134 prevalent and incident cases of anorectal CT, 7 (5.2%)
      were identified as LGV. None of the seven participants with LGV reported any
      symptoms. Two of the participants with LGV were simultaneously coinfected with
      rectal gonorrhoea. HIV coinfection was common among participants with both LGV
      (n=5, 71%) and non-LGV (n=98, 77%) serovars of CT (P=0.66). CONCLUSIONS:
      Anorectal LGV was uncommon but present among Nigerian MSM in this study.
      Consistent screening for L-serovars of CT, or presumptive treatment for LGV in
      cases with a high suspicion for this diagnosis, could potentially improve patient
      outcomes and decrease transmission.

PMID- 29378904
TI  - How can we increase offer rates of human papillomavirus (HPV) vaccination among
      men who have sex with men (MSM) in routine sexual health clinics?

PMID- 29378905
TI  - Overt Increase of Oxidative Stress and DNA Damage in Murine and Human Colitis and
      Colitis-Associated Neoplasia.
AB  - Patients with inflammatory bowel disease (IBD) have a higher risk of developing
      colitis-associated-cancer (CAC); however, the underlying processes of disease
      progression are not completely understood. Here, the molecular processes of
      inflammation-driven colon carcinogenesis were investigated using IL10-deficient
      mice (IL10 KO). IL10 KO mice were euthanized after development of colitis and
      dysplasia. IHC was performed for markers of colitis-induced DNA damage (CIDD):
      oxidative DNA lesions (8-oxoG), double-strand breaks (DSB; gammaH2AX). and DSB
      repair. MSI, LOH (Trp53, Apc), and global methylation (CIMP) were assessed on
      microdissected tissue. Comet assay for DNA damage, immunofluorescence, and
      immunoblotting were performed on intestinal organoids from wild-type (WT) and
      IL10 KO mice. Sequential biopsies and surgical specimens from IBD and CAC
      patients were used for IHC analysis. Severity of inflammation correlated with
      number of dysplasia. 8-oxoG and gammaH2AX-positive cells were significantly
      increased in inflamed and dysplastic areas along with activation of DSB repair.
      The amount of positively stained cells strongly correlated with degree of
      inflammation (8-oxoG: R = 0.923; gammaH2AX: R = 0.858). Neither CIMP, MSI nor LOH
      was observed. Enhanced DSBs in IL10 KO organoids were confirmed by comet assay
      and increased expression of gammaH2AX. Human clinical specimens exhibited
      significantly higher gammaH2AX and 8-oxoG in IBD, dysplasia, and CAC compared
      with normal mucosa. These data indicate that inflammation-driven colon
      carcinogenesis in IL10 KO mice and IBD patients is associated with oxidative DNA
      damage and overt presence of DSB. Mol Cancer Res; 16(4); 634-42. (c)2018 AACR.

PMID- 29378906
TI  - Association of USP10 with G3BP2 Inhibits p53 Signaling and Contributes to Poor
      Outcome in Prostate Cancer.
AB  - Ubiquitin-specific protease 10 (USP10) is known to deubiquitylate its target
      proteins, mainly to enhance their stabilities. USP10 maintains p53 protein levels
      and controls epigenetic changes induced by the androgen receptor (AR). GTPase
      activating protein-binding protein 2 (G3BP2), an androgen-responsive gene, is
      known as the main component of stress granules (SG) that interacts with USP10 in
      SGs. This study explores the roles of USP10 in prostate cancer progression in
      p53, G3BP2, and AR signaling. Using chromatin immunoprecipitation (ChIP) and
      sequence analysis, it was found that USP10 is transcriptionally induced with AR
      recruitment to an intronic region. Furthermore, USP10 regulates androgen-mediated
      signaling and cell growth. USP10 maintained G3BP2 protein stability by reducing
      polyubiquitylation. G3BP2-dependent growth activation and p53 nuclear export that
      reduced p53 signaling were repressed by USP10 knockdown. Clinically, USP10 was
      expressed primarily in the cytoplasm of prostate cancer tissues. High levels of
      USP10 expression were strongly correlated with high levels of AR, G3BP2, and p53
      in the cytoplasm. High expression of USP10 was significantly associated with poor
      prognosis of patients with prostate cancer. Taken together, USP10 has a
      repressive effect on p53 signaling for cell growth by regulating G3BP2
      expression. These findings highlight an important oncogenic aspect of USP10
      through its modulation of the p53-G3BP2 complex and AR signaling in prostate
      cancer.Implications: These findings elucidate the oncogenic role of USP10 in
      prostate cancer through an increase in G3BP2 protein that inhibits p53 activity,
      in addition to the promotion of AR signaling. Mol Cancer Res; 16(5); 846-56.
      (c)2018 AACR.

PMID- 29378908
TI  - The Transcription Factor AP4 Promotes Oncogenic Phenotypes and Cisplatin
      Resistance by Regulating LAPTM4B Expression.
AB  - Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a novel oncogene,
      whose overexpression is involved in cancer occurrence and progression. However,
      the mechanism of LAPTM4B transcriptional regulation remains unclear. In this
      study, the results of transcription factor (TF) profiling plate arrays indicated
      that AP4 was a potential transcription factor regulating LAPTM4B expression.
      LAPTM4B was positively correlated with AP4 and they were both associated with
      poor overall and disease-free survival. Luciferase and electrophoretic mobility
      shift assay assays confirmed that AP4 directly bound to the polymorphism region
      of LAPTM4B promoter and modulated its transcription. Functionally, AP4 promoted
      cell proliferation, migration, invasion, and assisted drug resistance in part
      through upregulation of LAPTM4B. Taken together, these findings identify LAPTM4B
      as a direct AP4 target gene and the interaction of AP4 and LAPTM4B plays an
      important role in breast cancer progression.Implications: This study demonstrates
      that AP4 promotes cell growth, migration, invasion, and cisplatin resistance
      through upregulation of LAPTM4B expression, thus representing an attractive
      therapeutic target for breast cancer. Mol Cancer Res; 16(5); 857-68. (c)2018
      AACR.

PMID- 29378909
TI  - Intracranial germinoma causing cerebral haemiatrophy and hypopituitarism.
AB  - A young woman presented with primary amenorrhoea, progressive haemiparesis,
      visual disturbance, dementia and focal motor seizures. Investigations showed
      hypopituitarism, unilateral cerebral atrophy and inflamed cerebrospinal fluid. A
      trans-sphenoidal biopsy gave a unifying diagnosis of a pituitary germinoma.

PMID- 29378907
TI  - Mitotically-Associated lncRNA (MANCR) Affects Genomic Stability and Cell Division
      in Aggressive Breast Cancer.
AB  - Aggressive breast cancer is difficult to treat as it is unresponsive to many
      hormone-based therapies; therefore, it is imperative to identify novel,
      targetable regulators of progression. Long non-coding RNAs (lncRNA) are important
      regulators in breast cancer and have great potential as therapeutic targets;
      however, little is known about how the majority of lncRNAs function within breast
      cancer. This study characterizes a novel lncRNA, MANCR (mitotically-associated
      long noncoding RNA; LINC00704), which is upregulated in breast cancer patient
      specimens and cells. Depletion of MANCR in triple-negative breast cancer cells
      significantly decreases cell proliferation and viability, with concomitant
      increases in DNA damage. Transcriptome analysis, based on RNA sequencing,
      following MANCR knockdown reveals significant differences in the expression of
      >2,000 transcripts, and gene set enrichment analysis identifies changes in
      multiple categories related to cell-cycle regulation. Furthermore, MANCR
      expression is highest in mitotic cells by both RT-qPCR and RNA in situ
      hybridization. Consistent with a role in cell-cycle regulation, MANCR-depleted
      cells have a lower mitotic index and higher incidences of defective cytokinesis
      and cell death. Taken together, these data reveal a role for the novel lncRNA,
      MANCR, in genomic stability of aggressive breast cancer, and identify it as a
      potential therapeutic target.Implications: The novel lncRNA, MANCR (LINC00704),
      is upregulated in breast cancer and is functionally linked with cell
      proliferation, viability, and genomic stability. Mol Cancer Res; 16(4); 587-98.
      (c)2018 AACR.

PMID- 29378912
TI  - Endoplasmic Reticulum-Bound Transcription Factor CREBH Stimulates RANKL-Induced
      Osteoclastogenesis.
AB  - Endoplasmic reticulum (ER) stress is triggered by various metabolic factors, such
      as cholesterol and proinflammatory cytokines. Recent studies have revealed that
      ER stress is closely related to skeletal disorders, such as osteoporosis.
      However, the precise mechanism by which ER stress regulates osteoclast
      differentiation has not been elucidated. In this study, we identified an ER-bound
      transcription factor, cAMP response element-binding protein H (CREBH), as a
      downstream effector of ER stress during RANKL-induced osteoclast differentiation.
      RANKL induced mild ER stress and the simultaneous accumulation of active nuclear
      CREBH (CREBH-N) in the nucleus during osteoclastogenesis. Overexpression of CREBH
      N in osteoclast precursors enhanced RANKL-induced osteoclast formation through
      NFATc1 upregulation. Inhibiting ER stress using a specific inhibitor attenuated
      the expression of osteoclast-related genes and CREBH activation. In addition,
      inhibition of reactive oxygen species using N-acetylcysteine attenuated ER
      stress, expression of osteoclast-specific marker genes, and RANKL-induced CREBH
      activation. Furthermore, inhibition of ER stress and CREBH signaling pathways
      using an ER stress-specific inhibitor or CREBH small interfering RNAs prevented
      RANKL-induced bone destruction in vivo. Taken together, our results suggest that
      reactive oxygen species/ER stress signaling-dependent CREBH activation plays an
      important role in RANKL-induced osteoclastogenesis. Therefore, inactivation of ER
      stress and CREBH signaling pathways may represent a new treatment strategy for
      osteoporosis.

PMID- 29378910
TI  - Mucosal-Associated Invariant T Cells Augment Immunopathology and Gastritis in
      Chronic Helicobacter pylori Infection.
AB  - Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and
      cytotoxic granzymes in response to by-products of microbial riboflavin synthesis.
      Although MAIT cells are protective against some pathogens, we reasoned that they
      might contribute to pathology in chronic bacterial infection. We observed MAIT
      cells in proximity to Helicobacter pylori bacteria in human gastric tissue, and
      so, using MR1-tetramers, we examined whether MAIT cells contribute to chronic
      gastritis in a mouse H. pylori SS1 infection model. Following infection, MAIT
      cells accumulated to high numbers in the gastric mucosa of wild-type C57BL/6
      mice, and this was even more pronounced in MAIT TCR transgenic mice or in C57BL/6
      mice where MAIT cells were preprimed by Ag exposure or prior infection. Gastric
      MAIT cells possessed an effector memory Tc1/Tc17 phenotype, and were associated
      with accelerated gastritis characterized by augmented recruitment of neutrophils,
      macrophages, dendritic cells, eosinophils, and non-MAIT T cells and by marked
      gastric atrophy. Similarly treated MR1-/- mice, which lack MAIT cells, showed
      significantly less gastric pathology. Thus, we demonstrate the pathogenic
      potential of MAIT cells in Helicobacter-associated immunopathology, with
      implications for other chronic bacterial infections.

PMID- 29378913
TI  - DDIT4 and Associated lncDDIT4 Modulate Th17 Differentiation through the
      DDIT4/TSC/mTOR Pathway.
AB  - Inflammation that complicates many autoimmune diseases, such as multiple
      sclerosis (MS), has been correlated to abnormal differentiation of Th17 cells.
      However, the reasons that promote Th17 cell-driven autoimmunity are yet to be
      discovered. In this study, we sought evidence that DNA-damage-inducible
      transcript 4 (DDIT4) and its associated long noncoding RNA DDIT4 (lncDDIT4)
      inhibit Th17 cell differentiation. We recruited 36 patients. Six MS patients and
      five healthy volunteers (controls) contributed PBMCs as material for microarray
      analysis. Microarray assays of lncDDIT4 and DDIT4 RNA expression identified
      outstanding differences between MS and control subjects, which were verified with
      real-time quantitative PCR. We then interrupted the expression of lncDDIT4 and
      DDIT4 mRNA in MS patients' naive CD4+ T cells and observed the resulting changes
      in Th17 cells. The expression of lncDDIT4 and DDIT4 mRNA were higher both in
      PBMCs and CD4+ T cells of MS patients than in healthy controls. DDIT4 (2.79-fold
      upregulation) was then recognized as a candidate for the cis-regulated target of
      lncDDIT4 (4.32-fold upregulation). Isolation of naive CD4+ T cells revealed
      enhanced levels of lncDDIT4 and DDIT4 after stimulated with Th17-inducing
      cytokines, but not after Th1, Th2, or T regulatory cell induction. Overexpression
      of lncDDIT4 in naive CD4+ T cells inhibited IL-17 transcription through increased
      DDIT4 expression and decreased activation of the DDIT4/mTOR pathway.
      Consistently, silencing lncDDIT4 in naive CD4+ T cells enhanced Th17
      differentiation through increased activation of the DDIT4/mTOR pathway. However,
      these results vanished when DDIT4 was silenced. This outcome suggests that
      lncDDIT4 regulates Th17 cell differentiation by directly targeting DDIT4.

PMID- 29378911
TI  - Massively Parallel Sequencing of Peritoneal and Splenic B Cell Repertoires
      Highlights Unique Properties of B-1 Cell Antibodies.
AB  - B-1 cells are a unique subset of B cells that are positively selected for
      expressing autoreactive BCRs. We isolated RNA from peritoneal (B-1a, B-1b, B-2)
      and splenic (B-1a, marginal zone, follicular) B cells from C57BL/6 mice and used
      5'-RACE to amplify the IgH V region using massively parallel sequencing. By
      analyzing 379,000 functional transcripts, we demonstrate that B-1a cells use a
      distinct and restricted repertoire. All B-1 cell subsets, especially peritoneal B
      1a cells, had a high proportion of sequences without N additions, suggesting
      predominantly prenatal development. Their transcripts differed markedly and
      uniquely contained VH11 and VH12 genes, which were rearranged only with a
      restricted selection of D and J genes, unlike other V genes. Compared to
      peritoneal B-1a, the peritoneal B-1b repertoire was larger, had little overlap
      with B-1a, and most sequences contained N additions. Similarly, the splenic B-1a
      repertoire differed from peritoneal B-1a sequences, having more unique sequences
      and more frequent N additions, suggesting influx of B-1a cells into the spleen
      from nonperitoneal sites. Two CDR3s, previously described as Abs to bromelain
      treated RBCs, comprised 43% of peritoneal B-1a sequences. We show that a single
      chain variable fragment designed after the most prevalent B-1a sequence bound
      oxidation-specific epitopes such as the phosphocholine of oxidized phospholipids.
      In summary, we provide the IgH V region library of six murine B cell subsets,
      including, to our knowledge for the first time, a comparison between B-1a and B
      1b cells, and we highlight qualities of B-1 cell Abs that indicate unique
      selection processes.

PMID- 29378914
TI  - Alveolar Macrophages Drive Hepatocellular Carcinoma Lung Metastasis by Generating
      Leukotriene B4.
AB  - Macrophages in lungs can be classified into two subpopulations, alveolar
      macrophages (AMs) and interstitial macrophages (IMs), which reside in the
      alveolar and interstitial spaces, respectively. Accumulating evidence indicates
      the involvement of IMs in lung metastasis, but the roles of AMs in lung
      metastasis still remain elusive. An i.v. injection of a mouse hepatocellular
      carcinoma (HCC) cell line, BNL, caused lung metastasis foci with infiltration of
      AMs and IMs. Comprehensive determination of arachidonic acid metabolite levels
      revealed increases in leukotrienes and PGs in lungs in this metastasis model. A 5
      lipoxygenase (LOX) inhibitor but not a cyclooxygenase inhibitor reduced the
      numbers of metastatic foci, particularly those of a larger size. A major 5-LOX
      metabolite, LTB4, augmented in vitro cell proliferation of human HCC cell lines
      as well as BNL cells. Moreover, in this lung metastasis course, AMs exhibited
      higher expression levels of the 5-LOX and LTB4 than IMs. Consistently, 5-LOX
      expressing AMs increased in the lungs of human HCC patients with lung metastasis,
      compared with those without lung metastasis. Furthermore, intratracheal
      clodronate liposome injection selectively depleted AMs but not IMs, together with
      reduced LTB4 content and metastatic foci numbers in this lung metastasis process.
      Finally, IMs in mouse metastatic foci produced CCL2, thereby recruiting blood
      borne, CCR2-expressing AMs into lungs. Thus, AMs can be recruited under the
      guidance of IM-derived CCL2 into metastatic lungs and can eventually contribute
      to the progression of lung metastasis by providing a potent arachidonic acid
      derived tumor growth promoting mediator, LTB4.

PMID- 29378916
TI  - Correction: Medical research and audit skills training for undergraduates: an
      international analysis and student-focused needs assessment.

PMID- 29378915
TI  - Cutting Edge: Nqo1 Regulates Irritant Contact Hypersensitivity against Croton Oil
      through Maintenance of Dendritic Epidermal T Cells.
AB  - Irritant contact dermatitis (ICD) is associated with local release of
      inflammatory mediators such as reactive oxygen species and regulated by various
      antioxidative enzymes and antioxidants. Although Nqo1 is involved in
      antioxidative reactions and detoxification, its role in ICD remains unknown. Nqo1
      deficient mice exhibited augmented ear swelling accompanied by neutrophil
      infiltration in the croton oil-induced mouse ICD model. In the skin of Nqo1
      deficient mice, Vgamma5Vdelta1+ dendritic epidermal T cells (DETCs), which are
      known to suppress ICD, were severely reduced. As the transfer of DETCs into Nqo1
      deficient mice reversed an increased ICD response, loss of DETCs could account
      for the increased ICD. DETCs from Nqo1-deficient mice were sensitive to oxidative
      stress-induced cell death in vitro, and antioxidant NAC treatment in the ears of
      these mice rescued the number of DETCs and produced a normal ICD response. Taken
      together, the current results demonstrate that antioxidative enzyme Nqo1
      regulates ICD through DETC maintenance.

PMID- 29378917
TI  - Sexual harassment of women in medicine: a problem for men to address.

PMID- 29378919
TI  - Hemorrhagic intraspinal paragonimiasis.

PMID- 29378920
TI  - Resident & Fellow Rounds.

PMID- 29378918
TI  - TMEM55a localizes to macrophage phagosomes to downregulate phagocytosis.
AB  - TMEM55a (also known as PIP4P2) is an enzyme that dephosphorylates the
      phosphatidylinositol (PtdIns) PtdIns(4,5)P2 to form PtdIns(5)P in vitro However,
      the in vivo conversion of the polyphosphoinositide into PtdIns(5)P by the
      phosphatase has not yet been demonstrated, and the role of TMEM55a remains poorly
      understood. Here, we found that mouse macrophages (Raw264.7) deficient in TMEM55a
      showed an increased engulfment of large particles without affecting the
      phagocytosis of Escherichia coli Transfection of a bacterial phosphatase with
      similar substrate specificity to TMEM55a, namely IpgD, into Raw264.7 cells
      inhibited the engulfment of IgG-erythrocytes in a manner dependent on its
      phosphatase activity. In contrast, cells transfected with PIP4K2a, which
      catalyzes PtdIns(4,5)P2 production from PtdIns(5)P, increased phagocytosis.
      Fluorescent TMEM55a transfected into Raw264.7 cells was found to mostly localize
      to the phagosome. The accumulation of PtdIns(4,5)P2, PtdIns(3,4,5)P3 and F-actin
      on the phagocytic cup was increased in TMEM55a-deficient cells, as monitored by
      live-cell imaging. Phagosomal PtdIns(5)P was decreased in the knockdown cells,
      but the augmentation of phagocytosis in these cells was unaffected by the
      exogenous addition of PtdIns(5)P. Taken together, these results suggest that
      TMEM55a negatively regulates the phagocytosis of large particles by reducing
      phagosomal PtdIns(4,5)P2 accumulation during cup formation.

PMID- 29378921
TI  - Mystery Case: A 48-year-old woman with bizarre behavior, neurologic symptoms, and
      progressive decline.

PMID- 29378922
TI  - Editors' note: Teaching NeuroImages: Amlodipine-responsive trigeminal neuralgia:
      An alibi for vascular compression theory.

PMID- 29378923
TI  - Reader response: Teaching NeuroImages: Amlodipine-responsive trigeminal
      neuralgia: An alibi for vascular compression theory.

PMID- 29378924
TI  - Author response: Teaching NeuroImages: Amlodipine-responsive trigeminal
      neuralgia: An alibi for vascular compression theory.

PMID- 29378926
TI  - Editors' note: Burnout, career satisfaction, and well-being among US neurology
      residents and fellows in 2016.

PMID- 29378925
TI  - Author response: Burnout, career satisfaction, and well-being among US neurology
      residents and fellows in 2016.

PMID- 29378927
TI  - Reader response: Burnout, career satisfaction, and well-being among US neurology
      residents and fellows in 2016.

PMID- 29378928
TI  - The Pediatric Stroke Outcome Measure: A predictor of outcome following arterial
      ischemic stroke.
AB  - OBJECTIVE: To evaluate the relationship between neurologic outcome at 1 month
      following diagnosis of pediatric arterial ischemic stroke (AIS) and motor and
      adaptive behavior outcomes at 12 months. METHODS: This prospective longitudinal
      observational cohort study recruited children from a single tertiary children's
      hospital diagnosed with first AIS between December 2007 and November 2013.
      Neurologic impairment was evaluated at 4 time points using the Pediatric Stroke
      Outcome Measure (PSOM) or Recovery and Recurrence Questionnaire following
      diagnosis of AIS (acute, 1, 6, and 12 months). Motor function and adaptive
      behavior were assessed at 12 months using standardized measures. Children were
      grouped for analysis, according to age at diagnosis (neonates vs preschool vs
      school-aged). The relationship between neurologic impairment and 12-month
      functional outcomes were examined. RESULTS: Sixty-four children were recruited
      (27 neonates, 19 preschool-aged, and 18 school-aged). Presence of impairment on
      the PSOM at 1 month was associated with lower 12-month fine motor z scores (p =
      0.004), gross motor z scores (p = 0.001), and adaptive behavior standard scores
      (p = 0.004). One-month PSOM impairment score was more predictive than age group
      or lesion size of 12-month motor and adaptive behavior outcome. CONCLUSIONS: The
      PSOM has value as a predictive tool when used at 1 month after first AIS
      diagnosed acutely in relation to motor and adaptive behavior, with variation
      according to age group.

PMID- 29378929
TI  - Clinical Reasoning: A 66-year-old woman with seizures and progressive right-sided
      weakness.

PMID- 29378930
TI  - Teaching NeuroImages: Congenital membrane causing unilateral hydrocephalus.

PMID- 29378931
TI  - Teaching NeuroImages: Atrophy in epileptic encephalopathy.

PMID- 29378932
TI  - Black patients missing out on stroke treatment.

PMID- 29378933
TI  - On the complex dynamics of savanna landscapes.
AB  - Simple mathematical models can exhibit rich and complex behaviors. Prototypical
      examples of these drawn from biology and other disciplines have provided insights
      that extend well beyond the situations that inspired them. Here, we explore a set
      of simple, yet realistic, models for savanna-forest vegetation dynamics based on
      minimal ecological assumptions. These models are aimed at understanding how
      vegetation interacts with both climate (a primary global determinant of
      vegetation structure) and feedbacks with chronic disturbances from fire. The
      model includes three plant functional types-grasses, savanna trees, and forest
      trees. Grass and (when they allow grass to persist in their subcanopy) savanna
      trees promote the spread of fires, which in turn, demographically limit trees.
      The model exhibits a spectacular range of behaviors. In addition to bistability,
      analysis reveals (i) that diverse cyclic behaviors (including limit and homo- and
      heteroclinic cycles) occur for broad ranges of parameter space, (ii) that large
      shifts in landscape structure can result from endogenous dynamics and not just
      from external drivers or from noise, and (iii) that introducing noise into this
      system induces resonant and inverse resonant phenomena, some of which have never
      been previously observed in ecological models. Ecologically, these results raise
      questions about how to evaluate complicated dynamics with data. Mathematically,
      they lead to classes of behaviors that are likely to occur in other models with
      similar structure.

PMID- 29378934
TI  - Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep
      brain.
AB  - Capabilities for recording neural activity in behaving mammals have greatly
      expanded our understanding of brain function. Some of the most sophisticated
      approaches use light delivered by an implanted fiber-optic cable to optically
      excite genetically encoded calcium indicators and to record the resulting changes
      in fluorescence. Physical constraints induced by the cables and the bulk, size,
      and weight of the associated fixtures complicate studies on natural behaviors,
      including social interactions and movements in environments that include
      obstacles, housings, and other complex features. Here, we introduce a wireless,
      injectable fluorescence photometer that integrates a miniaturized light source
      and a photodetector on a flexible, needle-shaped polymer support, suitable for
      injection into the deep brain at sites of interest. The ultrathin geometry and
      compliant mechanics of these probes allow minimally invasive implantation and
      stable chronic operation. In vivo studies in freely moving animals demonstrate
      that this technology allows high-fidelity recording of calcium fluorescence in
      the deep brain, with measurement characteristics that match or exceed those
      associated with fiber photometry systems. The resulting capabilities in optical
      recordings of neuronal dynamics in untethered, freely moving animals have
      potential for widespread applications in neuroscience research.

PMID- 29378935
TI  - RNA force field with accuracy comparable to state-of-the-art protein force
      fields.
AB  - Molecular dynamics (MD) simulation has become a powerful tool for characterizing
      at an atomic level of detail the conformational changes undergone by proteins.
      The application of such simulations to RNA structures, however, has proven more
      challenging, due in large part to the fact that the physical models ("force
      fields") available for MD simulations of RNA molecules are substantially less
      accurate in many respects than those currently available for proteins. Here, we
      introduce an extensive revision of a widely used RNA force field in which the
      parameters have been modified, based on quantum mechanical calculations and
      existing experimental information, to more accurately reflect the fundamental
      forces that stabilize RNA structures. We evaluate these revised parameters
      through long-timescale MD simulations of a set of RNA molecules that covers a
      wide range of structural complexity, including single-stranded RNAs, RNA
      duplexes, RNA hairpins, and riboswitches. The structural and thermodynamic
      properties measured in these simulations exhibited dramatically improved
      agreement with experimentally determined values. Based on the comparisons we
      performed, this RNA force field appears to achieve a level of accuracy comparable
      to that of state-of-the-art protein force fields, thus significantly advancing
      the utility of MD simulation as a tool for elucidating the structural dynamics
      and function of RNA molecules and RNA-containing biological assemblies.

PMID- 29378936
TI  - Child first language and adult second language are both tied to general-purpose
      learning systems.
AB  - Do the mechanisms underlying language in fact serve general-purpose functions
      that preexist this uniquely human capacity? To address this contentious and
      empirically challenging issue, we systematically tested the predictions of a well
      studied neurocognitive theory of language motivated by evolutionary principles.
      Multiple metaanalyses were performed to examine predicted links between language
      and two general-purpose learning systems, declarative and procedural memory. The
      results tied lexical abilities to learning only in declarative memory, while
      grammar was linked to learning in both systems in both child first language and
      adult second language, in specific ways. In second language learners, grammar was
      associated with only declarative memory at lower language experience, but with
      only procedural memory at higher experience. The findings yielded large effect
      sizes and held consistently across languages, language families, linguistic
      structures, and tasks, underscoring their reliability and validity. The results,
      which met the predicted pattern, provide comprehensive evidence that language is
      tied to general-purpose systems both in children acquiring their native language
      and adults learning an additional language. Crucially, if language learning
      relies on these systems, then our extensive knowledge of the systems from animal
      and human studies may also apply to this domain, leading to predictions that
      might be unwarranted in the more circumscribed study of language. Thus, by
      demonstrating a role for these systems in language, the findings simultaneously
      lay a foundation for potentially important advances in the study of this critical
      domain.

PMID- 29378937
TI  - High integrin alphaVbeta6 affinity reached by hybrid domain deletion slows ligand
      binding on-rate.
AB  - The role of the hybrid domain in integrin affinity regulation is unknown, as is
      whether the kinetics of ligand binding is modulated by integrin affinity state.
      Here, we compare cell surface and soluble integrin alphaVbeta6 truncation mutants
      for ligand-binding affinity, kinetics, and thermodynamics. Removal of the
      integrin transmembrane/cytoplasmic domains or lower legs has little effect on
      alphaVbeta6 affinity, in contrast to beta1 integrins. In integrin opening,
      rearrangement at the interface between the betaI and hybrid domains is linked to
      remodeling at the ligand-binding site at the opposite end of the betaI domain,
      which greatly increases in affinity in the open conformation. The larger size of
      the betaI-hybrid interface in the closed state suggests that the hybrid domain
      stabilizes closing. In agreement, deletion of the hybrid domain raised affinity
      by 50-fold. Surface plasmon resonance and isothermal titration calorimetry gave
      similar results and the latter revealed tradeoffs between enthalpy and entropy
      not apparent from affinity. At extremely high affinity reached in Mn2+ with
      hybrid domain truncation, alphaVbeta6 on-rate for both pro-TGF-beta1 and
      fibronectin declined. The results suggest that the open conformation of
      alphaVbeta6 has lower on-rate than the closed conformation, correlate with
      constriction of the ligand-binding pocket in open alphaVbeta6 structures, and
      suggest that the extended-closed conformation is kinetically selected for ligand
      binding. Subsequent transition to the extended-open conformation is stabilized by
      its much higher affinity for ligand and would also be stabilized by force exerted
      across ligand-bound integrins by the actin cytoskeleton.

PMID- 29378938
TI  - Insecurity, polio vaccination rates, and polio incidence in northwest Pakistan.
AB  - Pakistan is one of three countries in which endemic transmission of poliovirus
      has never been stopped. Insecurity is often cited but poorly studied as a barrier
      to eradicating polio. We analyzed routinely collected health data from 32
      districts of northwest Pakistan and constructed an index of insecurity based on
      journalistic reports of the monthly number of deaths and injuries resulting from
      conflict-related security incidents. The primary outcomes were the monthly
      incidence of paralytic polio cases within each district between 2007 and 2014 and
      the polio vaccination percentage from 666 district-level vaccination campaigns
      between 2007 and 2009, targeting ~5.7 million children. Multilevel Poisson
      regression controlling for time and district fixed effects was used to model the
      association between insecurity, vaccinator access, vaccination rates, and polio
      incidence. The number of children inaccessible to vaccinators was 19.7% greater
      (95% CI: 19.2-20.2%), and vaccination rates were 5.3% lower (95% CI: 5.2-5.3%) in
      "high-insecurity" campaigns compared with "secure" campaigns. The unadjusted mean
      vaccination rate was 96.3% (SD = 8.6) in secure campaigns and 88.3% (SD = 19.2)
      in high-insecurity campaigns. Polio incidence was 73.0% greater (95% CI: 30-131%)
      during high-insecurity months (unadjusted mean = 0.13 cases per million people,
      SD = 0.71) compared with secure months (unadjusted mean = 1.23 cases per million
      people, SD = 4.28). Thus, insecurity was associated with reduced vaccinator
      access, reduced polio vaccination, and increased polio incidence in northwest
      Pakistan. These findings demonstrate that insecurity is an important obstacle to
      global polio eradication.

PMID- 29378939
TI  - Range dynamics of mountain plants decrease with elevation.
AB  - Many studies report that mountain plant species are shifting upward in elevation.
      However, the majority of these reports focus on shifts of upper limits. Here, we
      expand the focus and simultaneously analyze changes of both range limits, optima,
      and abundances of 183 mountain plant species. We therefore resurveyed 1,576
      vegetation plots first recorded before 1970 in the European Alps. We found that
      both range limits and optima shifted upward in elevation, but the most pronounced
      trend was a mean increase in species abundance. Despite huge species-specific
      variation, range dynamics showed a consistent trend along the elevational
      gradient: Both range limits and optima shifted upslope faster the lower they were
      situated historically, and species' abundance increased more for species from
      lower elevations. Traits affecting the species' dispersal and persistence
      capacity were not related to their range dynamics. Using indicator values to
      stratify species by their thermal and nutrient demands revealed that elevational
      ranges of thermophilic species tended to expand, while those of cold-adapted
      species tended to contract. Abundance increases were strongest for nutriphilous
      species. These results suggest that recent climate warming interacted with
      airborne nitrogen deposition in driving the observed dynamics. So far, the
      majority of species appear as "winners" of recent changes, yet "losers" are
      overrepresented among high-elevation, cold-adapted species with low nutrient
      demands. In the decades to come, high-alpine species may hence face the double
      pressure of climatic changes and novel, superior competitors that move up faster
      than they themselves can escape to even higher elevations.

PMID- 29378940
TI  - Alarm calls evoke a visual search image of a predator in birds.
AB  - One of the core features of human speech is that words cause listeners to
      retrieve corresponding visual mental images. However, whether vocalizations
      similarly evoke mental images in animal communication systems is surprisingly
      unknown. Japanese tits (Parus minor) produce specific alarm calls when and only
      when encountering a predatory snake. Here, I show that simply hearing these calls
      causes tits to become more visually perceptive to objects resembling snakes.
      During playback of snake-specific alarm calls, tits approach a wooden stick being
      moved in a snake-like fashion. However, tits do not respond to the same stick
      when hearing other call types or if the stick's movement is dissimilar to that of
      a snake. Thus, before detecting a real snake, tits retrieve its visual image from
      snake-specific alarm calls and use this to search out snakes. This study provides
      evidence for a call-evoked visual search image in a nonhuman animal, offering a
      paradigm to explore the cognitive basis for animal vocal communication in the
      wild.

PMID- 29378941
TI  - In vivo wireless photonic photodynamic therapy.
AB  - An emerging class of targeted therapy relies on light as a spatially and
      temporally precise stimulus. Photodynamic therapy (PDT) is a clinical example in
      which optical illumination selectively activates light-sensitive drugs, termed
      photosensitizers, destroying malignant cells without the side effects associated
      with systemic treatments such as chemotherapy. Effective clinical application of
      PDT and other light-based therapies, however, is hindered by challenges in light
      delivery across biological tissue, which is optically opaque. To target deep
      regions, current clinical PDT uses optical fibers, but their incompatibility with
      chronic implantation allows only a single dose of light to be delivered per
      surgery. Here we report a wireless photonic approach to PDT using a miniaturized
      (30 mg, 15 mm3) implantable device and wireless powering system for light
      delivery. We demonstrate the therapeutic efficacy of this approach by activating
      photosensitizers (chlorin e6) through thick (>3 cm) tissues inaccessible by
      direct illumination, and by delivering multiple controlled doses of light to
      suppress tumor growth in vivo in animal cancer models. This versatility in light
      delivery overcomes key clinical limitations in PDT, and may afford further
      opportunities for light-based therapies.

PMID- 29378942
TI  - Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility.
AB  - The cellular and molecular basis of sex-dimorphic autoimmune diseases, such as
      the CNS demyelinating disease multiple sclerosis (MS), remains unclear. Our
      studies in the SJL mouse model of MS, experimental autoimmune encephalomyelitis
      (EAE), reveal that sex-determined differences in Il33 expression by innate immune
      cells in response to myelin peptide immunization regulate EAE susceptibility. IL
      33 is selectively induced in PLP139-151-immunized males and activates type 2
      innate lymphoid cells (ILC2s), cells that promote and sustain a nonpathogenic Th2
      myelin-specific response. Without this attenuating IL-33 response, females
      generate an encephalitogenic Th17-dominant response, which can be reversed by IL
      33 treatment. Mast cells are one source of IL-33 and we provide evidence that
      testosterone directly induces Il33 gene expression and also exerts effects on the
      potential for Il33 gene expression during mast cell development. Thus, in
      contrast to their pathogenic role in allergy, we propose a sex-specific role for
      both mast cells and ILC2s as attenuators of the pathogenic Th response in CNS
      inflammatory disease.

PMID- 29378944
TI  - High-resolution structure prediction of beta-barrel membrane proteins.
AB  - [Formula: see text]-Barrel membrane proteins ([Formula: see text]MPs) play
      important roles, but knowledge of their structures is limited. We have developed
      a method to predict their 3D structures. We predict strand registers and
      construct transmembrane (TM) domains of [Formula: see text]MPs accurately,
      including proteins for which no prediction has been attempted before. Our method
      also accurately predicts structures from protein families with a limited number
      of sequences and proteins with novel folds. An average main-chain rmsd of 3.48 A
      is achieved between predicted and experimentally resolved structures of TM
      domains, which is a significant improvement ([Formula: see text]3 A) over a
      recent study. For [Formula: see text]MPs with NMR structures, the deviation
      between predictions and experimentally solved structures is similar to the
      difference among the NMR structures, indicating excellent prediction accuracy.
      Moreover, we can now accurately model the extended [Formula: see text]-barrels
      and loops in non-TM domains, increasing the overall coverage of structure
      prediction by [Formula: see text]%. Our method is general and can be applied to
      genome-wide structural prediction of [Formula: see text]MPs.

PMID- 29378943
TI  - E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart,
      and bladder as well as in human lung and bladder cells.
AB  - E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the
      burning process. It contains neither carcinogenic incomplete combustion
      byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E
      cigarettes are promoted as safe and have gained significant popularity. In this
      study, instead of detecting nitrosamines, we directly measured DNA damage induced
      by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found
      mutagenic O6-methyldeoxyguanosines and gamma-hydroxy-1,N2 -propano
      deoxyguanosines in the lung, bladder, and heart. DNA-repair activity and repair
      proteins XPC and OGG1/2 are significantly reduced in the lung. We found that
      nicotine and its metabolite, nicotine-derived nitrosamine ketone, can induce the
      same effects and enhance mutational susceptibility and tumorigenic transformation
      of cultured human bronchial epithelial and urothelial cells. These results
      indicate that nicotine nitrosation occurs in vivo in mice and that E-cigarette
      smoke is carcinogenic to the murine lung and bladder and harmful to the murine
      heart. It is therefore possible that E-cigarette smoke may contribute to lung and
      bladder cancer, as well as heart disease, in humans.

PMID- 29378945
TI  - Adaptation of commensal proliferating Escherichia coli to the intestinal tract of
      young children with cystic fibrosis.
AB  - The mature human gut microbiota is established during the first years of life,
      and altered intestinal microbiomes have been associated with several human health
      disorders. Escherichia coli usually represents less than 1% of the human
      intestinal microbiome, whereas in cystic fibrosis (CF), greater than 50% relative
      abundance is common and correlates with intestinal inflammation and fecal fat
      malabsorption. Despite the proliferation of E. coli and other Proteobacteria in
      conditions involving chronic gastrointestinal tract inflammation, little is known
      about adaptation of specific characteristics associated with microbiota clonal
      expansion. We show that E. coli isolated from fecal samples of young children
      with CF has adapted to growth on glycerol, a major component of fecal fat. E.
      coli isolates from different CF patients demonstrate an increased growth rate in
      the presence of glycerol compared with E. coli from healthy controls, and
      unrelated CF E. coli strains have independently acquired this growth trait.
      Furthermore, CF and control E. coli isolates have differential gene expression
      when grown in minimal media with glycerol as the sole carbon source. While CF
      isolates display a growth-promoting transcriptional profile, control isolates
      engage stress and stationary-phase programs, which likely results in slower
      growth rates. Our results indicate that there is selection of unique
      characteristics within the microbiome of individuals with CF, which could
      contribute to individual disease outcomes.

PMID- 29378946
TI  - Method to generate highly stable D-amino acid analogs of bioactive helical
      peptides using a mirror image of the entire PDB.
AB  - Biologics are a rapidly growing class of therapeutics with many advantages over
      traditional small molecule drugs. A major obstacle to their development is that
      proteins and peptides are easily destroyed by proteases and, thus, typically have
      prohibitively short half-lives in human gut, plasma, and cells. One of the most
      effective ways to prevent degradation is to engineer analogs from dextrorotary
      (D)-amino acids, with up to 105-fold improvements in potency reported. We here
      propose a general peptide-engineering platform that overcomes limitations of
      previous methods. By creating a mirror image of every structure in the Protein
      Data Bank (PDB), we generate a database of ~2.8 million D-peptides. To obtain a D
      analog of a given peptide, we search the (D)-PDB for similar configurations of
      its critical-"hotspot"-residues. As a proof of concept, we apply our method to
      two peptides that are Food and Drug Administration approved as therapeutics for
      diabetes and osteoporosis, respectively. We obtain D-analogs that activate the
      GLP1 and PTH1 receptors with the same efficacy as their natural counterparts and
      show greatly increased half-life.

PMID- 29378947
TI  - Superresolution imaging of individual replication forks reveals unexpected
      prodrug resistance mechanism.
AB  - Many drugs require extensive metabolism en route to their targets. High
      resolution visualization of prodrug metabolism should therefore utilize analogs
      containing a small modification that does not interfere with its metabolism or
      mode of action. In addition to serving as mechanistic probes, such analogs
      provide candidates for theranostics when applied in both therapeutic and
      diagnostic modalities. Here a traceable mimic of the widely used anticancer
      prodrug cytarabine (ara-C) was generated by converting a single hydroxyl group to
      azide, giving "AzC." This compound exhibited the same biological profile as ara-C
      in cell cultures and zebrafish larvae. Using azide-alkyne "click" reactions, we
      uncovered an apparent contradiction: drug-resistant cells incorporated relatively
      large quantities of AzC into their genomes and entered S-phase arrest, whereas
      drug-sensitive cells incorporated only small quantities of AzC. Fluorescence
      microscopy was used to elucidate structural features associated with drug
      resistance by characterizing the architectures of stalled DNA replication foci
      containing AzC, EdU, gammaH2AX, and proliferating cell nuclear antigen (PCNA).
      Three-color superresolution imaging revealed replication foci containing one,
      two, or three partially resolved replication forks. Upon removing AzC from the
      media, resumption of DNA synthesis and completion of the cell cycle occurred
      before complete removal of AzC from genomes in vitro and in vivo. These results
      revealed an important mechanism for the low toxicity of ara-C toward normal
      tissues and drug-resistant cancer cells, where its efficient incorporation into
      DNA gives rise to highly stable, stalled replication forks that limit further
      incorporation of the drug, yet allow for the resumption of DNA synthesis and
      cellular division following treatment.

PMID- 29378949
TI  - Field migration rates of tidal meanders recapitulate fluvial morphodynamics.
AB  - The majority of tidal channels display marked meandering features. Despite their
      importance in oil-reservoir formation and tidal landscape morphology, questions
      remain on whether tidal-meander dynamics could be understood in terms of fluvial
      processes and theory. Key differences suggest otherwise, like the periodic
      reversal of landscape-forming tidal flows and the widely accepted empirical
      notion that tidal meanders are stable landscape features, in stark contrast with
      their migrating fluvial counterparts. On the contrary, here we show that, once
      properly normalized, observed migration rates of tidal and fluvial meanders are
      remarkably similar. Key to normalization is the role of tidal channel width that
      responds to the strong spatial gradients of landscape-forming flow rates and
      tidal prisms. We find that migration dynamics of tidal meanders agree with
      nonlinear theories for river meander evolution. Our results challenge the
      conventional view of tidal channels as stable landscape features and suggest that
      meandering tidal channels recapitulate many fluvial counterparts owing to large
      gradients of tidal prisms across meander wavelengths.

PMID- 29378948
TI  - LncRNA IDH1-AS1 links the functions of c-Myc and HIF1alpha via IDH1 to regulate
      the Warburg effect.
AB  - The oncoprotein c-Myc plays an important role in regulating glycolysis under
      normoxia; yet, in cancer cells, HIF1alpha, which is essential for driving
      glycolysis under hypoxia, is often up-regulated even in the presence of oxygen.
      The relationship between these two major regulators of the Warburg effect remains
      to be fully defined. Here we demonstrate that regulation of a long noncoding RNA
      (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1alpha in
      activating the Warburg effect under normoxia. c-Myc transcriptionally repressed
      IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus
      enhanced its enzymatic activity. This resulted in increased alpha-KG and
      decreased ROS production and subsequent HIF1alpha down-regulation, leading to
      attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes
      activation of the Warburg effect by HIF1alpha. As such, IDH1-AS1 overexpression
      inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell
      proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may
      therefore represent a potential metabolic approach for cancer treatment.

PMID- 29378950
TI  - K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin
      chains.
AB  - Different polyubiquitin chain linkages direct substrates toward distinct cellular
      pathways. K63-linked ubiquitylation is known to regulate proteasome-independent
      events such as signal transduction, but its function in the context of
      heterogeneous ubiquitin chains remains unclear. Here, we report that K63
      ubiquitylation plays a critical role in proteasome-mediated substrate degradation
      by serving as a "seed" for K48/K63 branched ubiquitin chains. Quantitative
      analysis revealed that K48/K63 branched linkages preferentially associate with
      proteasomes in cells. We found that ITCH-dependent K63 ubiquitylation of the
      proapoptotic regulator TXNIP triggered subsequent assembly of K48/K63 branched
      chains by recruiting ubiquitin-interacting ligases such as UBR5, leading to TXNIP
      degradation. These results reveal a role for K63 chains as a substrate-specific
      mark for proteasomal degradation involved in regulating cell fate. Our findings
      provide insight into how cellular interpretation of the ubiquitin code is altered
      by combinations of ubiquitin linkages.

PMID- 29378951
TI  - Holo-lipocalin-2-derived siderophores increase mitochondrial ROS and impair
      oxidative phosphorylation in rat cardiomyocytes.
AB  - Lipocalin-2 (Lcn2), a critical component of the innate immune response which
      binds siderophores and limits bacterial iron acquisition, can elicit spillover
      adverse proinflammatory effects. Here we show that holo-Lcn2 (Lcn2-siderophore
      iron, 1:3:1) increases mitochondrial reactive oxygen species (ROS) generation and
      attenuates mitochondrial oxidative phosphorylation in adult rat primary
      cardiomyocytes in a manner blocked by N-acetyl-cysteine or the mitochondria
      specific antioxidant SkQ1. We further demonstrate using siderophores 2,3-DHBA
      (2,3-dihydroxybenzoic acid) and 2,5-DHBA that increased ROS and reduction in
      oxidative phosphorylation are direct effects of the siderophore component of holo
      Lcn2 and not due to apo-Lcn2 alone. Extracellular apo-Lcn2 enhanced the potency
      of 2,3-DHBA and 2,5-DHBA to increase ROS production and decrease mitochondrial
      respiratory capacity, whereas intracellular apo-Lcn2 attenuated these effects.
      These actions of holo-Lcn2 required an intact plasma membrane and were decreased
      by inhibition of endocytosis. The hearts, but not serum, of Lcn2 knockout (LKO)
      mice contained lower levels of 2,5-DHBA compared with wild-type hearts.
      Furthermore, LKO mice were protected from ischemia/reperfusion-induced cardiac
      mitochondrial dysfunction. Our study identifies the siderophore moiety of holo
      Lcn2 as a regulator of cardiomyocyte mitochondrial bioenergetics.

PMID- 29378953
TI  - Disease-causing mutation in alpha-actinin-4 promotes podocyte detachment through
      maladaptation to periodic stretch.
AB  - alpha-Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer
      mechanical resilience to the reconstituted actin network. How this resilience is
      built and dynamically regulated in the podocyte, and the cause of its failure in
      ACTN4 mutation-associated focal segmental glomerulosclerosis (FSGS), remains
      poorly defined. Using primary podocytes isolated from wild-type (WT) and FSGS
      causing point mutant Actn4 knockin mice, we report responses to periodic stretch.
      While WT cells largely maintained their F-actin cytoskeleton and contraction,
      mutant cells developed extensive and irrecoverable reductions in these same
      properties. This difference was attributable to both actin material changes and a
      more spatially correlated intracellular stress in mutant cells. When stretched
      cells were further challenged using a cell adhesion assay, mutant cells were more
      likely to detach. Together, these data suggest a mechanism for mutant podocyte
      dysfunction and loss in FSGS-it is a direct consequence of mechanical responses
      of a cytoskeleton that is brittle.

PMID- 29378954
TI  - Automated monitoring of behavior reveals bursty interaction patterns and rapid
      spreading dynamics in honeybee social networks.
AB  - Social networks mediate the spread of information and disease. The dynamics of
      spreading depends, among other factors, on the distribution of times between
      successive contacts in the network. Heavy-tailed (bursty) time distributions are
      characteristic of human communication networks, including face-to-face contacts
      and electronic communication via mobile phone calls, email, and internet
      communities. Burstiness has been cited as a possible cause for slow spreading in
      these networks relative to a randomized reference network. However, it is not
      known whether burstiness is an epiphenomenon of human-specific patterns of
      communication. Moreover, theory predicts that fast, bursty communication networks
      should also exist. Here, we present a high-throughput technology for automated
      monitoring of social interactions of individual honeybees and the analysis of a
      rich and detailed dataset consisting of more than 1.2 million interactions in
      five honeybee colonies. We find that bees, like humans, also interact in bursts
      but that spreading is significantly faster than in a randomized reference network
      and remains so even after an experimental demographic perturbation. Thus, while
      burstiness may be an intrinsic property of social interactions, it does not
      always inhibit spreading in real-world communication networks. We anticipate that
      these results will inform future models of large-scale social organization and
      information and disease transmission, and may impact health management of
      threatened honeybee populations.

PMID- 29378952
TI  - OLT1177, a beta-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3
      inflammasome and reverses the metabolic cost of inflammation.
AB  - Activation of the NLRP3 inflammasome induces maturation of IL-1beta and IL-18,
      both validated targets for treating acute and chronic inflammatory diseases.
      Here, we demonstrate that OLT1177, an orally active beta-sulfonyl nitrile
      molecule, inhibits activation of the NLRP3 inflammasome. In vitro, nanomolar
      concentrations of OLT1177 reduced IL-1beta and IL-18 release following canonical
      and noncanonical NLRP3 inflammasome activation. The molecule showed no effect on
      the NLRC4 and AIM2 inflammasomes, suggesting specificity for NLRP3. In LPS
      stimulated human blood-derived macrophages, OLT1177 decreased IL-1beta levels by
      60% and IL-18 by 70% at concentrations 100-fold lower in vitro than plasma
      concentrations safely reached in humans. OLT1177 also reduced IL-1beta release
      and caspase-1 activity in freshly obtained human blood neutrophils. In monocytes
      isolated from patients with cryopyrin-associated periodic syndrome (CAPS),
      OLT1177 inhibited LPS-induced IL-1beta release by 84% and 36%.
      Immunoprecipitation and FRET analysis demonstrated that OLT1177 prevented NLRP3
      ASC, as well as NLRP3-caspase-1 interaction, thus inhibiting NLRP3 inflammasome
      oligomerization. In a cell-free assay, OLT1177 reduced ATPase activity of
      recombinant NLRP3, suggesting direct targeting of NLRP3. Mechanistically, OLT1177
      did not affect potassium efflux, gene expression, or synthesis of the IL-1beta
      precursor. Steady-state levels of phosphorylated NF-kappaB and IkB kinase were
      significantly lowered in spleen cells from OLT1177-treated mice. We observed
      reduced IL-1beta content in tissue homogenates, limited oxidative stress, and
      increased muscle oxidative metabolism in OLT1177-treated mice challenged with
      LPS. Healthy humans receiving 1,000 mg of OLT1177 daily for 8 d exhibited neither
      adverse effects nor biochemical or hematological changes.

PMID- 29378955
TI  - Neuronal control of astrocytic respiration through a variant of the Crabtree
      effect.
AB  - Aerobic glycolysis is a phenomenon that in the long term contributes to synaptic
      formation and growth, is reduced by normal aging, and correlates with amyloid
      beta deposition. Aerobic glycolysis starts within seconds of neural activity and
      it is not obvious why energetic efficiency should be compromised precisely when
      energy demand is highest. Using genetically encoded FRET nanosensors and real
      time oxygen measurements in culture and in hippocampal slices, we show here that
      astrocytes respond to physiological extracellular K+ with an acute rise in
      cytosolic ATP and a parallel inhibition of oxygen consumption, explained by
      glycolytic stimulation via the Na+-bicarbonate cotransporter NBCe1. This control
      of mitochondrial respiration via glycolysis modulation is reminiscent of a
      phenomenon previously described in proliferating cells, known as the Crabtree
      effect. Fast brain aerobic glycolysis may be interpreted as a strategy whereby
      neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing
      information processing.

PMID- 29378956
TI  - ATR-Chk1 activation mitigates replication stress caused by mismatch repair
      dependent processing of DNA damage.
AB  - The mismatch repair pathway (MMR) is essential for removing DNA polymerase
      errors, thereby maintaining genomic stability. Loss of MMR function increases
      mutation frequency and is associated with tumorigenesis. However, how MMR is
      executed at active DNA replication forks is unclear. This has important
      implications for understanding how MMR repairs O6-methylguanine/thymidine (MeG/T)
      mismatches created upon exposure to DNA alkylating agents. If MeG/T lesion
      recognition by MMR initiates mismatch excision, the reinsertion of a mismatched
      thymidine during resynthesis could initiate futile repair cycles. One consequence
      of futile repair cycles might be a disruption of overall DNA replication in the
      affected cell. Herein, we show that in MMR-proficient HeLa cancer cells,
      treatment with a DNA alkylating agent slows S phase progression, yet cells still
      progress into the next cell cycle. In the first S phase following treatment, they
      activate ataxia telangiectasia and Rad3-related (ATR)-Checkpoint Kinase 1 (Chk1)
      signaling, which limits DNA damage, while inhibition of ATR kinase activity
      accelerates DNA damage accumulation and sensitivity to the DNA alkylating agent.
      We also observed that exposure of human embryonic stem cells to alkylation damage
      severely compromised DNA replication in a MMR-dependent manner. These cells fail
      to activate the ATR-Chk1 signaling axis, which may limit their ability to handle
      replication stress. Accordingly, they accumulate double-strand breaks and undergo
      immediate apoptosis. Our findings implicate the MMR-directed response to
      alkylation damage as a replication stress inducer, suggesting that repeated MMR
      processing of mismatches may occur that can disrupt S phase progression.

PMID- 29378957
TI  - AtCAP2 is crucial for lytic vacuole biogenesis during germination by positively
      regulating vacuolar protein trafficking.
AB  - Protein trafficking is a fundamental mechanism of subcellular organization and
      contributes to organellar biogenesis. AtCAP2 is an Arabidopsis homolog of the
      Mesembryanthemum crystallinum calcium-dependent protein kinase 1 adaptor protein
      2 (McCAP2), a member of the syntaxin superfamily. Here, we show that AtCAP2 plays
      an important role in the conversion to the lytic vacuole (LV) during early plant
      development. The AtCAP2 loss-of-function mutant atcap2-1 displayed delays in
      protein storage vacuole (PSV) protein degradation, PSV fusion, LV acidification,
      and biosynthesis of several vacuolar proteins during germination. At the mature
      stage, atcap2-1 plants accumulated vacuolar proteins in the prevacuolar
      compartment (PVC) instead of the LV. In wild-type plants, AtCAP2 localizes to the
      PVC as a peripheral membrane protein and in the PVC compartment recruits
      glyceraldehyde-3-phosphate dehydrogenase C2 (GAPC2) to the PVC. We propose that
      AtCAP2 contributes to LV biogenesis during early plant development by supporting
      the trafficking of specific proteins involved in the PSV-to-LV transition and LV
      acidification during early stages of plant development.

PMID- 29378958
TI  - TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain.
AB  - The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in
      nociceptors where, when activated by chemical or thermal stimuli, it functions as
      an important transducer of painful and itch-related stimuli. Although the
      interaction of TRPV1 with proteins that regulate its function has been previously
      explored, their modulation by chaperones has not been elucidated, as is the case
      for other mammalian TRP channels. Here we show that TRPV1 physically interacts
      with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an
      antagonist of Sig-1R and an important neurosteroid associated to the modulation
      of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of
      TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a
      decrease in capsaicin-induced nociceptive responses. This is observed both in
      males treated with a synthetic antagonist of Sig-1R and in pregnant females where
      progesterone levels are elevated. This constitutes a previously undescribed
      mechanism by which TRPV1-dependent nociception and pain can be regulated.

PMID- 29378959
TI  - Effects of rapamycin on growth hormone receptor knockout mice.
AB  - It is well documented that inhibition of mTORC1 (defined by Raptor), a complex of
      mechanistic target of rapamycin (mTOR), extends life span, but less is known
      about the mechanisms by which mTORC2 (defined by Rictor) impacts longevity. Here,
      rapamycin (an inhibitor of mTOR) was used in GHR-KO (growth hormone receptor
      knockout) mice, which have suppressed mTORC1 and up-regulated mTORC2 signaling,
      to determine the effect of concurrently decreased mTORC1 and mTORC2 signaling on
      life span. We found that rapamycin extended life span in control normal (N) mice,
      whereas it had the opposite effect in GHR-KO mice. In the rapamycin-treated GHR
      KO mice, mTORC2 signaling was reduced without further inhibition of mTORC1 in the
      liver, muscle, and s.c. fat. Glucose and lipid homeostasis were impaired, and old
      GHR-KO mice treated with rapamycin lost functional immune cells and had increased
      inflammation. In GHR-KO MEF cells, knockdown of Rictor, but not Raptor, decreased
      mTORC2 signaling. We conclude that drastic reduction of mTORC2 plays important
      roles in impaired longevity in GHR-KO mice via disruption of whole-body
      homeostasis.

PMID- 29378960
TI  - Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar Abeta by multiple
      endoproteolytic cleavages within the beta-sheet domain.
AB  - Accumulation of amyloid-beta (Abeta), which is associated with Alzheimer's
      disease, can be caused by excess production or insufficient clearance. Because of
      its beta-sheet structure, fibrillar Abeta is resistant to proteolysis, which
      would contribute to slow degradation of Abeta plaques in vivo. Fibrillar Abeta
      can be internalized by microglia, which are the scavenger cells of the brain, but
      the fibrils are degraded only slowly in microglial lysosomes. Cathepsin B is a
      lysosomal protease that has been shown to proteolyze fibrillar Abeta. Tripeptidyl
      peptidase 1 (TPP1), a lysosomal serine protease, possesses endopeptidase activity
      and has been shown to cleave peptides between hydrophobic residues. Herein, we
      demonstrate that TPP1 is able to proteolyze fibrillar Abeta efficiently. Mass
      spectrometry analysis of peptides released from fibrillar Abeta digested with
      TPP1 reveals several endoproteolytic cleavages including some within beta-sheet
      regions that are important for fibril formation. Using molecular dynamics
      simulations, we demonstrate that these cleavages destabilize fibrillar beta-sheet
      structure. The demonstration that TPP1 can degrade fibrillar forms of Abeta
      provides insight into the turnover of fibrillar Abeta and may lead to new
      therapeutic methods to increase degradation of Abeta plaques.

PMID- 29378961
TI  - Myopic (HD-PTP, PTPN23) selectively regulates synaptic neuropeptide release.
AB  - Neurotransmission is mediated by synaptic exocytosis of neuropeptide-containing
      dense-core vesicles (DCVs) and small-molecule transmitter-containing small
      synaptic vesicles (SSVs). Exocytosis of both vesicle types depends on Ca2+ and
      shared secretory proteins. Here, we show that increasing or decreasing expression
      of Myopic (mop, HD-PTP, PTPN23), a Bro1 domain-containing pseudophosphatase
      implicated in neuronal development and neuropeptide gene expression, increases
      synaptic neuropeptide stores at the Drosophila neuromuscular junction (NMJ). This
      occurs without altering DCV content or transport, but synaptic DCV number and age
      are increased. The effect on synaptic neuropeptide stores is accounted for by
      inhibition of activity-induced Ca2+-dependent neuropeptide release. cAMP-evoked
      Ca2+-independent synaptic neuropeptide release also requires optimal Myopic
      expression, showing that Myopic affects the DCV secretory machinery shared by
      cAMP and Ca2+ pathways. Presynaptic Myopic is abundant at early endosomes, but
      interaction with the endosomal sorting complex required for transport III (ESCRT
      III) protein (CHMP4/Shrub) that mediates Myopic's effect on neuron pruning is not
      required for control of neuropeptide release. Remarkably, in contrast to the
      effect on DCVs, Myopic does not affect release from SSVs. Therefore, Myopic
      selectively regulates synaptic DCV exocytosis that mediates peptidergic
      transmission at the NMJ.

PMID- 29378963
TI  - Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila
      melanogaster.
AB  - Sirtuins are an evolutionarily conserved family of NAD+-dependent deacylases that
      control metabolism, stress response, genomic stability, and longevity. Here, we
      show the sole mitochondrial sirtuin in Drosophila melanogaster, Sirt4, regulates
      energy homeostasis and longevity. Sirt4 knockout flies have a short lifespan,
      with increased sensitivity to starvation and decreased fertility and activity. In
      contrast, flies overexpressing Sirt4 either ubiquitously or specifically in the
      fat body are long-lived. Despite rapid starvation, Sirt4 knockout flies
      paradoxically maintain elevated levels of energy reserves, including lipids,
      glycogen, and trehalose, while fasting, suggesting an inability to properly
      catabolize stored energy. Metabolomic analysis indicates several specific
      pathways are affected in Sirt4 knockout flies, including glycolysis, branched
      chain amino acid metabolism, and impaired catabolism of fatty acids with chain
      length C18 or greater. Together, these phenotypes point to a role for Sirt4 in
      mediating the organismal response to fasting, and ensuring metabolic homeostasis
      and longevity.

PMID- 29378962
TI  - Disruption of the anaphase-promoting complex confers resistance to TTK inhibitors
      in triple-negative breast cancer.
AB  - TTK protein kinase (TTK), also known as Monopolar spindle 1 (MPS1), is a key
      regulator of the spindle assembly checkpoint (SAC), which functions to maintain
      genomic integrity. TTK has emerged as a promising therapeutic target in human
      cancers, including triple-negative breast cancer (TNBC). Several TTK inhibitors
      (TTKis) are being evaluated in clinical trials, and an understanding of the
      mechanisms mediating TTKi sensitivity and resistance could inform the successful
      development of this class of agents. We evaluated the cellular effects of the
      potent clinical TTKi CFI-402257 in TNBC models. CFI-402257 induced apoptosis and
      potentiated aneuploidy in TNBC lines by accelerating progression through mitosis
      and inducing mitotic segregation errors. We used genome-wide CRISPR/Cas9 screens
      in multiple TNBC cell lines to identify mechanisms of resistance to CFI-402257.
      Our functional genomic screens identified members of the anaphase-promoting
      complex/cyclosome (APC/C) complex, which promotes mitotic progression following
      inactivation of the SAC. Several screen candidates were validated to confer
      resistance to CFI-402257 and other TTKis using CRISPR/Cas9 and siRNA methods.
      These findings extend the observation that impairment of the APC/C enables cells
      to tolerate genomic instability caused by SAC inactivation, and support the
      notion that a measure of APC/C function could predict the response to TTK
      inhibition. Indeed, an APC/C gene expression signature is significantly
      associated with CFI-402257 response in breast and lung adenocarcinoma cell line
      panels. This expression signature, along with somatic alterations in genes
      involved in mitotic progression, represent potential biomarkers that could be
      evaluated in ongoing clinical trials of CFI-402257 or other TTKis.

PMID- 29378964
TI  - Stimulus generalization as a mechanism for learning to trust.
AB  - How do humans learn to trust unfamiliar others? Decisions in the absence of
      direct knowledge rely on our ability to generalize from past experiences and are
      often shaped by the degree of similarity between prior experience and novel
      situations. Here, we leverage a stimulus generalization framework to examine how
      perceptual similarity between known individuals and unfamiliar strangers shapes
      social learning. In a behavioral study, subjects play an iterative trust game
      with three partners who exhibit highly trustworthy, somewhat trustworthy, or
      highly untrustworthy behavior. After learning who can be trusted, subjects select
      new partners for a second game. Unbeknownst to subjects, each potential new
      partner was parametrically morphed with one of the three original players.
      Results reveal that subjects prefer to play with strangers who implicitly
      resemble the original player they previously learned was trustworthy and avoid
      playing with strangers resembling the untrustworthy player. These decisions to
      trust or distrust strangers formed a generalization gradient that converged
      toward baseline as perceptual similarity to the original player diminished. In a
      second imaging experiment we replicate these behavioral gradients and leverage
      multivariate pattern similarity analyses to reveal that a tuning profile of
      activation patterns in the amygdala selectively captures increasing perceptions
      of untrustworthiness. We additionally observe that within the caudate adaptive
      choices to trust rely on neural activation patterns similar to those elicited
      when learning about unrelated, but perceptually familiar, individuals. Together,
      these findings suggest an associative learning mechanism efficiently deploys
      moral information encoded from past experiences to guide future choice.

PMID- 29378965
TI  - Disruption of the ciliary GTPase Arl13b suppresses Sonic hedgehog overactivation
      and inhibits medulloblastoma formation.
AB  - Medulloblastoma (MB) is the most common malignant pediatric brain tumor, and
      overactivation of the Sonic Hedgehog (Shh) signaling pathway, which requires the
      primary cilium, causes 30% of MBs. Current treatments have known negative side
      effects or resistance mechanisms, so new treatments are necessary. Shh signaling
      mutations, like those that remove Patched1 (Ptch1) or activate Smoothened (Smo),
      cause tumors dependent on the presence of cilia. Genetic ablation of cilia
      prevents these tumors by removing Gli activator, but cilia are a poor therapeutic
      target since they support many biological processes. A more appropriate strategy
      would be to identify a protein that functionally disentangles Gli activation and
      ciliogenesis. Our mechanistic understanding of the ciliary GTPase Arl13b predicts
      that it could be such a target. Arl13b mutants retain short cilia, and loss of
      Arl13b results in ligand-independent, constitutive, low-level pathway activation
      but prevents maximal signaling without disrupting Gli repressor. Here, we show
      that deletion of Arl13b reduced Shh signaling levels in the presence of oncogenic
      SmoA1, suggesting Arl13b acts downstream of known tumor resistance mechanisms.
      Knockdown of ARL13B in human MB cell lines and in primary mouse MB cell culture
      decreased proliferation. Importantly, loss of Arl13b in a Ptch1-deleted mouse
      model of MB inhibited tumor formation. Postnatal depletion of Arl13b does not
      lead to any overt phenotypes in the epidermis, liver, or cerebellum. Thus, our in
      vivo and in vitro studies demonstrate that disruption of Arl13b inhibits cilia
      dependent oncogenic Shh overactivation.

PMID- 29378966
TI  - Economic value of ecological information in ecosystem-based natural resource
      management depends on exploitation history.
AB  - Ecosystem approaches to natural resource management are seen as a way to provide
      better outcomes for ecosystems and for people, yet the nature and strength of
      interactions among ecosystem components is usually unknown. Here we characterize
      the economic benefits of ecological knowledge through a simple model of fisheries
      that target a predator (piscivore) and its prey. We solve for the management
      (harvest) trajectory that maximizes net present value (NPV) for different
      ecological interactions and initial conditions that represent different levels of
      exploitation history. Optimal management trajectories generally approached
      similar harvest levels, but the pathways toward those levels varied considerably
      by ecological scenario. Application of the wrong harvest trajectory, which would
      happen if one type of ecological interaction were assumed but in fact another
      were occurring, generally led to only modest reductions in NPV. However, the
      risks were not equal across fleets: risks of incurring large losses of NPV and
      missing management targets were much higher in the fishery targeting piscivores,
      especially when piscivores were heavily depleted. Our findings suggest that the
      ecosystem approach might provide the greatest benefits when used to identify
      system states where management performs poorly with imperfect knowledge of system
      linkages so that management strategies can be adopted to avoid those states.

PMID- 29378967
TI  - Neutrophils recruited through high endothelial venules of the lymph nodes via
      PNAd intercept disseminating Staphylococcus aureus.
AB  - Staphylococcus aureus is a skin- and respiratory tract-colonizing bacterium and
      is the leading cause of community-acquired skin infections. Dissemination of
      these bacteria into systemic circulation causes bacteremia, which has a high
      mortality rate. Therefore, understanding the immunologic barriers that prevent
      dissemination is critical to developing novel treatments. In this study, we
      demonstrate that an S. aureus breach across skin leads to some migration of the
      pathogen to the draining lymph node, but no further. While subcapsular sinus
      (SCS) macrophage in lymph nodes were important in detaining S. aureus, a rapid
      complement-dependent neutrophil recruitment (independent of the SCS macrophage)
      via high endothelial venules (HEVs) resulted in high numbers of neutrophils that
      intercepted the bacteria in the lymph nodes. Peripheral Node Addressin together
      with its two ligands, L-selectin and platelet P-selectin, are critical for
      recruiting neutrophils via the HEVs. Almost no neutrophils entered the lymph
      nodes via lymphatics. Neutrophils actively phagocytosed S. aureus and helped
      sterilize the lymph nodes and prevent dissemination to blood and other organs.

PMID- 29378969
TI  - Ocean acidification affects coral growth by reducing skeletal density.
AB  - Ocean acidification (OA) is considered an important threat to coral reef
      ecosystems, because it reduces the availability of carbonate ions that reef
      building corals need to produce their skeletons. However, while theory predicts
      that coral calcification rates decline as carbonate ion concentrations decrease,
      this prediction is not consistently borne out in laboratory manipulation
      experiments or in studies of corals inhabiting naturally low-pH reefs today. The
      skeletal growth of corals consists of two distinct processes: extension (upward
      growth) and densification (lateral thickening). Here, we show that skeletal
      density is directly sensitive to changes in seawater carbonate ion concentration
      and thus, to OA, whereas extension is not. We present a numerical model of
      Porites skeletal growth that links skeletal density with the external seawater
      environment via its influence on the chemistry of coral calcifying fluid. We
      validate the model using existing coral skeletal datasets from six Porites
      species collected across five reef sites and use this framework to project the
      impact of 21st century OA on Porites skeletal density across the global tropics.
      Our model predicts that OA alone will drive up to 20.3 +/- 5.4% decline in the
      skeletal density of reef-building Porites corals.

PMID- 29378971
TI  - Triangular cyclic rotaxanes: Size, fluctuations, and switching properties.
AB  - We examine one of the simplest cyclic rotaxanes-a molecule made from three rods
      with variable length between 0 and L. This [3]rotaxane, unlike a traditional
      molecule, shows significant size and shape fluctuations. We quantify these using
      a number of different measures. In particular, we show that the average angles
      are [Formula: see text], and [Formula: see text] and the most populated lengths
      lie at [Formula: see text], and [Formula: see text] The triangles are usually
      obtuse. We discuss the area allowed within the triangle for inclusion compounds.
      Inspired by the linear rotaxane switches, we also consider the statistical
      mechanics of switching when stations with attractive interactions promote small
      cycle areas.

PMID- 29378968
TI  - Hippocampal expression of a virus-derived protein impairs memory in mice.
AB  - The analysis of the biology of neurotropic viruses, notably of their interference
      with cellular signaling, provides a useful tool to get further insight into the
      role of specific pathways in the control of behavioral functions. Here, we
      exploited the natural property of a viral protein identified as a major effector
      of behavioral disorders during infection. We used the phosphoprotein (P) of Borna
      disease virus, which acts as a decoy substrate for protein kinase C (PKC) when
      expressed in neurons and disrupts synaptic plasticity. By a lentiviral-based
      strategy, we directed the singled-out expression of P in the dentate gyrus of the
      hippocampus and we examined its impact on mouse behavior. Mice expressing the P
      protein displayed increased anxiety and impaired long-term memory in contextual
      and spatial memory tasks. Interestingly, these effects were dependent on P
      protein phosphorylation by PKC, as expression of a mutant form of P devoid of its
      PKC phosphorylation sites had no effect on these behaviors. We also revealed
      features of behavioral impairment induced by P protein expression but that were
      independent of its phosphorylation by PKC. Altogether, our findings provide
      insight into the behavioral correlates of viral infection, as well as into the
      impact of virus-mediated alterations of the PKC pathway on behavioral functions.

PMID- 29378972
TI  - Impact of the Use of Intravascular Imaging on Patients Who Underwent Orbital
      Atherectomy.
AB  - OBJECTIVES: We assessed the impact of intravascular ultrasound (IVUS)/optical
      coherence tomography (OCT) on outcomes of patients who underwent orbital
      atherectomy. BACKGROUND: Intravascular imaging provides enhanced lesion
      morphology assessment and optimization of percutaneous coronary intervention
      (PCI) outcomes. Severe coronary artery calcification increases the complexity of
      PCI and is associated with worse clinical outcomes. Orbital atherectomy modifies
      calcified plaque, facilitating stent delivery and optimizing stent expansion. The
      impact of IVUS/OCT on clinical outcomes after orbital atherectomy is unknown.
      METHODS: Of the 458 consecutive real-world patients in our retrospective
      multicenter registry, a total of 138 patients (30.1%) underwent orbital
      atherectomy with IVUS/OCT. The primary safety endpoint was the rate of 30-day
      major adverse cardiac and cerebrovascular events, comprised of death, myocardial
      infarction (MI), target-vessel revascularization (TVR), and stroke. RESULTS: The
      IVUS/OCT group and no-imaging group had similar rates of the primary endpoint
      (1.5% vs 2.5%; P=.48) as well as death (1.5% vs 1.3%; P=.86), MI (1.5% vs 0.9%;
      P=.63), TVR (0% vs 0%; P=NS), and stroke (0% vs 0.3%; P=.51). The 30-day stent
      thrombosis rates were low in both groups (0.7% vs 0.9%; P=.82). Emergent coronary
      artery bypass graft surgery was uncommonly performed in both groups (0.0% vs
      0.9%; P=.25). CONCLUSION: Orbital atherectomy guided by intravascular imaging is
      feasible and safe. A large prospective randomized trial is needed to determine
      the clinical benefit of IVUS/OCT during PCI with orbital atherectomy.

PMID- 29378970
TI  - Landau-Ginzburg theory of cortex dynamics: Scale-free avalanches emerge at the
      edge of synchronization.
AB  - Understanding the origin, nature, and functional significance of complex patterns
      of neural activity, as recorded by diverse electrophysiological and neuroimaging
      techniques, is a central challenge in neuroscience. Such patterns include
      collective oscillations emerging out of neural synchronization as well as highly
      heterogeneous outbursts of activity interspersed by periods of quiescence, called
      "neuronal avalanches." Much debate has been generated about the possible scale
      invariance or criticality of such avalanches and its relevance for brain
      function. Aimed at shedding light onto this, here we analyze the large-scale
      collective properties of the cortex by using a mesoscopic approach following the
      principle of parsimony of Landau-Ginzburg. Our model is similar to that of Wilson
      Cowan for neural dynamics but crucially, includes stochasticity and space;
      synaptic plasticity and inhibition are considered as possible regulatory
      mechanisms. Detailed analyses uncover a phase diagram including down-state,
      synchronous, asynchronous, and up-state phases and reveal that empirical findings
      for neuronal avalanches are consistently reproduced by tuning our model to the
      edge of synchronization. This reveals that the putative criticality of cortical
      dynamics does not correspond to a quiescent-to-active phase transition as usually
      assumed in theoretical approaches but to a synchronization phase transition, at
      which incipient oscillations and scale-free avalanches coexist. Furthermore, our
      model also accounts for up and down states as they occur (e.g., during deep
      sleep). This approach constitutes a framework to rationalize the possible
      collective phases and phase transitions of cortical networks in simple terms,
      thus helping to shed light on basic aspects of brain functioning from a very
      broad perspective.

PMID- 29378973
TI  - Multimodality Imaging and Percutaneous Closure of a Large Left Main Coronary
      Artery to Superior Vena Cava Fistula.
AB  - Images illustrate 3D reconstruction CT showing fistula arising from the left main
      coronary artery draining into the superior vena cava. Additional angiographic
      images show the fistula before and after percutaneous closure with Amplatzer
      Vascular plugs.

PMID- 29378974
TI  - Coronary Artery Straightening Causing Acute Severe Mitral Regurgitation.
AB  - A 79-year-old woman had an atretic LIMA to LAD but without significant LAD
      stenosis, patent SVG to OM1, patent SVG to RCA, and severe tandem lesions in a
      very tortuous LCX for which she underwent PCI. Placement of a BMW coronary
      guidewire into the LCX resulted in the straightening of the vessel.

PMID- 29378975
TI  - Unusual Case of Three Total Occlusions.
AB  - This case highlights the value of extensive coronary collaterals in maintaining
      myocardial viability in severe coronary artery disease, and the role of cardiac
      MRI in guiding revascularization decisions.

PMID- 29378976
TI  - Thromboembolic Occlusion of the Left Coronary Artery During Transcatheter Aortic
      Valve Implantation.
AB  - Non-cerebral thromboembolic complications of transcatheter aortic valve
      implantation are rare, but life threatening. We report a 62-year-old woman with
      aortic stenosis who qualified for TAVI due to obesity and developed hypotension
      and bradycardia as a result of thromboembolic occlusion of the LCA.

PMID- 29378977
TI  - Real-time classification of auditory sentences using evoked cortical activity in
      humans.
AB  - OBJECTIVE: Recent research has characterized the anatomical and functional basis
      of speech perception in the human auditory cortex. These advances have made it
      possible to decode speech information from activity in brain regions like the
      superior temporal gyrus, but no published work has demonstrated this ability in
      real-time, which is necessary for neuroprosthetic brain-computer interfaces.
      APPROACH: Here, we introduce a real-time neural speech recognition (rtNSR)
      software package, which was used to classify spoken input from high-resolution
      electrocorticography signals in real-time. We tested the system with two human
      subjects implanted with electrode arrays over the lateral brain surface. Subjects
      listened to multiple repetitions of ten sentences, and rtNSR classified what was
      heard in real-time from neural activity patterns using direct sentence-level and
      HMM-based phoneme-level classification schemes. MAIN RESULTS: We observed single
      trial sentence classification accuracies of [Formula: see text] or higher for
      each subject with less than 7 minutes of training data, demonstrating the ability
      of rtNSR to use cortical recordings to perform accurate real-time speech decoding
      in a limited vocabulary setting. SIGNIFICANCE: Further development and testing of
      the package with different speech paradigms could influence the design of future
      speech neuroprosthetic applications.

PMID- 29378978
TI  - Fluorescence properties of Yb</sup><sup>3+</sup> - Er</sup><sup>3+</sup> co-doped
      phosphate glasses containing silver nanoparticles.
AB  - Er </sup><sup>3+</sup> - Yb </sup><sup>3+ </sup> co-doped phosphate glasses, also
      containing silver nitrate (SN), were fabricated. Transmission electron microscopy
      (TEM) and X-ray photoelectron spectroscopy (XPS) analyses were used to evidence
      the nucleation and presence of silver nanoparticles (SNP).&#13; The basic
      parameters of the glasses were inspected by means of absorption and fluorescence
      spectra and fluorescence lifetimes under "indirect" excitation at 916 nm (in-band
      of Yb</sup><sup>3+</sup>) and at 406 nm (in-band of surface plasmon resonance
      given by the presence of SNP). The spectra as well as estimates for the basic
      parameters defining the lasing/amplifying potential of these glasses were studied
      in function of SN concentration. The experimental results indicate that by
      increasing the SN content an enhancement of Er</sup><sup>3+</sup> /
      Yb</sup><sup>3+</sup> fluorescence is produced.

PMID- 29378979
TI  - The translucency effect of different colored resin cements used with zirconia
      core and titanium abutments.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of the different
      color of resin cements and zirconia cores on the translucency parameter (TP) of
      the restoration that simulates the implant-supported fixed prosthesis using
      titanium base on the bottom. MATERIALS AND METHODS: Zirconia core plates (Zr
      Zahn) were prepared in A2 shades (n = 11). Resin cement plates (3M ESPE) were
      prepared in A2, A1, translucent (TR) shades (n = 11). The initial color
      measurements and were measured on zirconia core plates, and resin cements plates
      using a spectrophotometer. Then, the resin cement plates were placed below the
      zirconia core plates, and the second measurements were done. The final
      measurements were done after placing the titanium discs in the bottom. The data
      were analyzed with two-way analysis of variance and Tukey honestly significant
      differences tests (alpha = 0.05). RESULTS: The highest TP values were recorded
      for A1-colored resin specimens and the lowest for zirconia core plates in the
      first measurement (P < 0.05). The addition of zirconia core decreased the TP
      values in all tested resin cement groups (P < 0.05). The highest TP value was
      recorded for A1-colored resin cement with zirconia core plates and the lowest for
      A2 and TR with zirconia core plates after second measurements (P < 0.05). The
      addition of titanium decreased the TP of the zirconia core plate and resin cement
      combination (P < 0.05). CONCLUSIONS: The addition of a zirconia core under the
      resin cement dramatically reduced the TP values, and the presence of a titanium
      layer decreased the TP value and caused a darker appearance.

PMID- 29378980
TI  - The prevalence of osteoporosis among antenatal clinic attendees in a rural
      mission hospital in South-East Nigeria.
AB  - INTRODUCTION: Osteoporosis is a global public health problem characterized by
      reduction of bone mineral density (BMD). This study aimed to assess the
      prevalence of osteoporosis among antenatal clinic attendees in a rural
      Southeastern hospital. MATERIAL AND METHODS: This was a cross-sectional study of
      booking Antenatal Clinic Attendees at Mile 4 Catholic Hospital, Abakaliki,
      between October 2014 and February 2015. The study participants were selected
      through systematic random sampling. The BMD of the right calcaneal bone of the
      participants was measured using the OsteoPro, a Quantitative ultrasound scan.
      RESULTS: A total of 327 eligible women participated in the study. The average age
      of the participants was 29 +/- 4.5 years. The average parity was 2 +/- 1.6
      childbirths. The mean T-score was -1.19 +/- 4.9. Osteoporosis and osteopenia were
      recorded in 119 women (36.4%) and 56 women (17.1%), respectively, whereas 152
      (46.5%) were within normal range. History of regular exercise by the respondents
      is statistically significant on the reduction of osteopenia and osteoporosis (P
      <= 0.05). The history of ever use of calcium supplementation by the study
      participants in the index pregnancy did not have any significant effect on the
      reduction of osteoporosis. CONCLUSION: There is a high prevalence of osteoporosis
      among pregnant women in Southeast Nigeria. This may be due to the predominant
      poor adherence and low dose of calcium supplementation among pregnant women in
      this environment. Therefore, there is an urgent need for sensitization on this
      public health problem.

PMID- 29378981
TI  - Evaluation of antimicrobial and thermal effects of diode laser on root canal
      dentin.
AB  - OBJECTIVES: The aim of this study was to evaluate the antimicrobial effects of
      diode laser and temperature rise on the root surface during application.
      MATERIALS AND METHODS: Thirty-six teeth were chemomechanically prepared and
      irrigated with 2.5% sodium hypochlorite and 17% ethylenediaminetetraacetic acid,
      and then autoclaved and incubated with a suspension of Enterococcus faecalis. The
      specimens were randomly divided into three groups (n = 12): Group 1, irradiated
      by diode laser at 1.2 W; Group 2, irradiated by diode laser at 2 W; and Group 3,
      irradiated by diode laser at 3 W. The grown bacteria were counted and the mean
      numbers of the each test tube were determined. The temperature was measured on
      the external apical third of the root during laser application. The mean values
      of results for each group were compared using one-way analysis of variance and
      Tukey test. RESULTS: No significant difference was obtained among the test groups
      in terms of the colony counts (P > 0.05). According to the temperature changes,
      there was a significant difference between groups (P < 0.05). Temperature rises
      were 16.79 degrees C, 10.20 degrees C, and 6.25 degrees C in Group 3, Group 2,
      and Group 1, respectively. CONCLUSION: Diode laser irradiation with 1.2 W
      demonstrated comparable performance with 2 W and 3 W power sets for elimination
      of E. faecalis from root canal with less temperature rise.

PMID- 29378982
TI  - An evaluation of effects of platelet-rich-fibrin on postoperative morbidities
      after lower third molar surgery.
AB  - OBJECTIVES: The aim of the present study was to assess whether the use of
      platelet-rich fibrin (PRF) decreased the pain, swelling, and trismus levels of
      postoperative third molar surgery. MATERIALS AND METHODS: In a double-blinded,
      split-mouth randomized study, thirty patients (6 male/24 female, mean age 20.32
      years) with bilateral symmetric impacted third molars were enrolled in this study
      to receive surgery. The PRF mass was randomly placed in one of the extraction
      sockets, whereas the other socket was left without treatment. The outcome
      variables were pain, maximum mouth opening (trismus), swelling (edema), and the
      presence of dry socket which were measured using a 10-point visual analog scale,
      manual calipers, and 3dMD facial imaging system which was used for the 1st time
      in the third molar surgery. RESULTS: Statistical analyses revealed that there
      were no significant differences between the control and study groups regarding
      postoperative pain, swelling, and trismus (P > 0.05). CONCLUSION: The results of
      this study suggest that PRF was not observed to have a positive effect on
      postoperative discomfort, so even though, PRF is presumed to have positive
      effects on healing and recovery processes.

PMID- 29378983
TI  - Time interval to initiation of contraceptive methods following childbirth in a
      low-resource setting.
AB  - OBJECTIVES: The objectives of the study were to determine factors affecting the
      interval between a woman's last childbirth and the initiation of contraception.
      MATERIALS AND METHODS: This was a retrospective study. Family planning clinic
      records of the Barau Dikko Teaching Hospital Kaduna from January 2000 to March
      2014 were retrieved. Information was collected on demographics, reproductive, and
      contraceptive history. Data were analyzed using the SPSS version 15 software, and
      missing responses were excluded. Chi-square was used as a test of association
      with significance level established at P = 0.05. RESULTS: A total of 5992
      client's cards were retrieved. All were female and married. Majority were aged 25
      34 years (53.1%), had completed secondary education (56%) and were Muslims
      (52.3%). Only 4979 cards (83.1%) had correct data on intervals and 22.1% of these
      clients initiated contraception within 6 months of their last childbirth.
      Education, religion, source of information, number of living children, desire to
      have more children, previous use of contraception, and type of contraception
      chosen were significantly associated with intervals for initiating contraception
      after last childbirth (P < 0.05) while the presence of complications in the last
      delivery was not (P > 0.05). CONCLUSIONS: Majority of women initiate
      contraception late after childbirth in this setting. Increased awareness on
      immediate/early postpartum contraception is required. Further qualitative studies
      will help to explore findings of this study.

PMID- 29378984
TI  - Risk factors for diabetes mellitus among adult residents of a rural District in
      Southern Nigeria: Implications for prevention and control.
AB  - INTRODUCTION: Diabetes Mellitus is a non-communicable disease that affects people
      worldwide and poses major public health and socioeconomic challenges. METHODS:
      This was a descriptive cross-sectional community based survey carried out in
      Abua, a rural district located in the Niger Delta region of Nigeria among 462
      adults recruited through multi-stage sampling. Data was collected using the
      structured WHO STEPS instrument for Chronic Disease Risk Factor Surveillance. The
      questionnaire included questions that assessed socio-demographic characteristics,
      diabetic risk factors, anthropometric measures, and biochemical parameters.
      Fasting blood glucose and blood pressure was measured using the WHO
      recommendations. RESULTS: Equal number of males and females aged between 18 and
      82 years were recruited. Mean age of 40.4614.36 years and median age of 38.5
      years. The prevalence of diabetes mellitus was 37 (8.0%), of which 28 (6.1%) were
      previously diagnosed while 9 (1.9%) were newly diagnosed. Alcohol intake (AOR =
      10.69; 95% CI = 2.60-43.87; P = 0.001) physical activity (AOR = 4.78; 95% CI =
      1.16-19.65; P = 0.03), diastolic blood pressure (AOR= 32.67; 95% CI = 3.68
      289.65; P = 0.002), age and family history of DM showed significant independent
      association (OR 1.09, 95% CI: 0.000, P < 0.001, OR 0.072, 95% CI: 0.014-0.380, P
      = 0.007) with diabetes mellitus. CONCLUSION: Study findings underscore the need
      for diabetes prevention and control activities that address the four major risk
      factors identified by WHO. These interventions will positively impact prevalence
      of diabetes and other NCDs. Intervention strategies should not only target urban
      populations but also focus on education and health promotion among rural
      populations in a bid to forestall rising prevalence of diabetes.

PMID- 29378985
TI  - Evaluation of accessory mental foramina morphology with cone-beam computed
      tomography.
AB  - BACKGROUND: Accessory mental foramen (AMF) is the extra mental foramen (MF)
      located in the mandible. The recognition of AMF is important to avoid
      complications during surgical procedures involving MF and cheeks. AIM: This study
      aimed to determine the prevalence, localization, and size of AMF by using cone
      beam computed tomography (CBCT). MATERIALS AND METHODS: CBCT images of 645
      patients over 13-14 years (male 281; female 364) were retrospectively evaluated.
      The CBCT images were obtained using Promax 3D(r) (Planmeca, Helsinki, Finland)
      device with automated exposure parameters varying depending on the cases.
      Statistical analysis was performed using descriptive statistics, chi-square test
      and t-test. RESULTS: AMF was detected in 75 (11.6%) patients. There was no
      significant difference between the presence of AMF and gender (P = 0.57, P >
      0.05). Majority of the cases (n = 67, 88.8%) consisted of single AMF, while
      double AMF was observed in 6 (10%) and triple AMF in 2 (1.2%) patients. The most
      common location of AMF with respect to MF was posterio-inferior (n = 57, 67.1%),
      and AMF placed at the root line of first molar tooth in 45 cases (52.9%).
      CONCLUSION: AMF can be seen in the mandible one in every ten patients being
      single in most cases. Considering the high prevalence and present morphological
      features, AMF should be detected by CBCT before surgical operations, particularly
      in implant planning for the prevention of possible complications.

PMID- 29378986
TI  - Evaluation of apically extruded debris and irrigant using different file systems.
AB  - OBJECTIVE: The aim of this study was to evaluate the amount of apically extruded
      debris and irrigant during cleaning and shaping with different file systems.
      MATERIALS AND METHODS: Seventy-five extracted mandibular premolar and canine
      teeth were randomly divided into five groups (n = 15). The root canals were
      instrumented by using Mtwo (VDW, Munich, Germany), Twisted File (TF; Sybron Endo,
      Orange, California, USA), Reciproc (VDW), Self-Adjusting File (SAF; Re Dent-Nova,
      Ra'anana, Israel) systems, and K-type stainless steel hand file (Mani Inc.,
      Tochigi, Japan). Apically extruded debris was collected and dried in preweighed
      Eppendorf tubes. Extruded irrigant was collected from the cannula by using a
      plastic insulin syringe. After drying, the amount of apically extruded debris was
      established by subtracting the initial weight from the final weight of the tubes.
      After performing the Kolmogorov-Smirnov test, data were analyzed by Kruskall
      Wallis test at a significance level of P value less than 0.05. RESULTS: There
      were no statistically significant differences between the file systems in terms
      of debris and irrigant extrusion. Mtwo group produced the highest mean debris
      extrusion value and the TF group produced the less compared with the other files.
      The least mean irrigant extrusion value was associated with the SAF group,
      whereas the highest mean irrigant extrusion value was associated with the
      Reciproc group. CONCLUSION: Under the conditions of the study, all file systems
      were associated with apical debris and irrigant extrusion.

PMID- 29378987
TI  - Incidence of postoperative residual paralysis in a nigerian teaching hospital.
AB  - BACKGROUND: Postoperative residual paralysis (PORP) is a known risk factor after
      general anesthesia (GA) for critical respiratory events and increased
      postoperative morbidity. PORP is defined as a train-of-four ratio (TOFR) of <0.9
      using acceleromyography (AMG). TOFR <0.9 has been associated with increased risk
      of aspiration, obstruction of the upper airway and an impaired hypoxic
      ventilatory response. AIM: The aim of this study was to determine the incidence
      of PORP, associated factors related with its occurrence and critical respiratory
      events in the postanesthesia recovery room (PAR) at our institution. METHODOLOGY:
      Forty-one adult patients were scheduled for elective surgeries requiring GA with
      the use of at least 1 dose of a nondepolarizing neuromuscular blocking drug
      (NMBD). An independent anesthetist quantitatively measured TOFR of recruited
      patients postoperatively in the recovery room using the TOF-watch SX
      acceleromyograph (Organon Teknika) 5 min after arrival. RESULTS: The incidence of
      PORP was 75.6% (n = 31), with severe PORP (TOFR <0.7) seen in 41.5% (n = 17) of
      patients. Median time to full recovery in the PAR was 33 min (range 5-164 min).
      There was no statistical difference in the incidence of PORP related to the
      choice of NMBD (P = 0.186) or duration of surgery (P = 0.175). No respiratory
      complications or events were observed in patients with residual blockade.
      CONCLUSION: The incidence of PORP is quite high and undetected in our
      environment. Quantitative monitoring for residual paralysis is advocated as part
      of routine monitoring with the use of NMBDs for improved patient safety.

PMID- 29378988
TI  - Dentin permeability of carious primary teeth.
AB  - BACKGROUND: Many in vitro studies have used dentine permeability to evaluate the
      efficacy of various restorative and preventative procedures. The easiest way to
      evaluate dentine permeability is to calculate its hydraulic conductance (Lp)
      using fluid filtration methods. Research has examined electronic hydraulic
      conductance measurement methods that give more precise and reliable results for
      the permeability of dentine than the classical method. To our knowledge, no study
      has examined the dentine permeability of carious primary teeth. AIM: This in
      vitro study determined the dentine permeability of carious primary molars
      precisely with a new electronic hydraulic conductance measurement system and
      compared them with healthy primary molars. DESIGN: The study examined 60 carious
      and noncarious primary second molars with no restorations, fractures, or cracks
      at different root resorption stages. RESULTS: The results showed that the dentine
      permeability increased with the severity of caries in primary teeth. CONCLUSION:
      The dentine permeability of carious primary teeth was higher than that of
      noncarious primary teeth. Therefore, treatment of primary teeth should be
      performed more quickly.

PMID- 29378989
TI  - Investigation of In vitro Mineral forming bacterial isolates from supragingival
      calculus.
AB  - AIM: Although it is known that bacterial mechanisms are involved in dental
      calculus formation, which is a predisposing factor in periodontal diseases, there
      have been few studies of such associations, and therefore, information available
      is limited. The purpose of this study was to isolate and identify aerobic
      bacteria responsible for direct calcification from supragingival calculus
      samples. MATERIALS AND METHODS: The study was conducted using supragingival
      calculus samples from patients with periodontal disease, which was required as
      part of conventional treatment. Isolations were performed by sampling the
      supragingival calculus with buffer and inoculating the samples on media on which
      crystallization could be observed. The 16S recombinant DNA of the obtained pure
      cultures was then amplified and sequenced. RESULTS: A few bacterial species that
      have not previously been associated with mineralization or identified on
      bacterial plaque or calculus were detected. The bacteria that caused
      mineralization an aerobic environment are identified as Neisseria flava,
      Aggregatibacter segnis, Streptococcus tigurinus, and Morococcus cerebrosus.
      CONCLUSION: These findings proved that bacteria potentially play a role in the
      etiopathology of supragingival calculus. The association between the effects of
      the identified bacteria on periodontal diseases and calculus formation requires
      further studies.

PMID- 29378990
TI  - Prevalence and correlates of complementary and alternative medicine use among
      cancer patients in usmanu danfodiyo university teaching hospital, Sokoto,
      Nigeria.
AB  - BACKGROUND: The rate of complementary and alternative medicine (CAM) use among
      cancer patients is on the increase worldwide. This is due to the innate urge
      among humans to try new and alternative ways of medicine, especially where
      conventional medicine failed to provide satisfactory solution such as in sickle
      cell disease and cancer. OBJECTIVE: To assess the prevalence and correlates of
      CAM use among cancer patients in Usmanu Danfodiyo University Teaching Hospital
      (UDUTH), Sokoto, Nigeria. MATERIALS AND METHODS: A cross-sectional study was
      conducted among 240 cancer patients selected by systematic sampling technique
      from July to September 2016. Data were collected using a semi-structured
      standardized questionnaire. RESULTS: The mean age of the study participants was
      45 +/- 13.7 years. Majority, 159 (66.3%) of the 240 respondents, were CAM users,
      with the most common methods being prayer (30.8%) and herbal therapy (28.3%).
      Majority of CAM users (64.2%) did not derive any benefit from CAM use, but rather
      reported adverse effects such as nausea and vomiting (52.5%) and diarrhea
      (44.2%). Physicians were unaware of CAM use in most cases (87.4%), and this was
      majorly attributed to the physicians not asking them about CAM use. Male sex and
      absence of comorbidities were the predictors of CAM use identified. CONCLUSION:
      The prevalence of CAM use is high among cancer patients in UDUTH, Sokoto,
      Nigeria, but the physicians were largely unaware of CAM use due to communication
      gap. These findings underscore the need for physicians to consistently ask their
      patients on CAM use, while government should enact laws regulating CAM use in
      Nigeria.

PMID- 29378991
TI  - Postoperative analgesia using bupivacaine wound infiltration with intravenous
      tramadol or dexamethasone following obstetric spinal anaesthesia.
AB  - CONTEXT: Effective management of postcesarean section (CS) pain is important for
      the well-being of mother and child; even in limited-resource areas, there are
      drug options which can be explored to achieve this. AIM: This study aimed to
      compare the analgesic effects of a combination of bupivacaine wound infiltration
      with either intravenous (IV) dexamethasone or tramadol after CS. SETTING AND
      DESIGN: This study was a randomized, double-blind, comparative study in a
      tertiary hospital. Clearance obtained from the Institution's Ethics and Research
      Committee. METHODS: One hundred and twenty American Society of Anesthesiologists
      I or II pregnant women scheduled for CS under spinal anesthesia were recruited
      after giving consent. At the end of skin closure, all the patients received 20 ml
      of 0.1% plain bupivacaine for wound infiltration and IV dexamethasone 8 mg (Group
      BD) or tramadol 100 mg (Group BT). Outcome measures were time to first analgesic
      request, visual analog scale (VAS) scores, side effects, and patients'
      satisfaction. RESULTS: Time to first analgesic request was 3.2 +/- 1.87 and 3.3
      +/- 2.01 h for BD and BT groups, respectively (P = 0.778). VAS scores for the
      first 2 h were lower in the bupivacaine/tramadol group compared to
      bupivacaine/dexamethasone group; the differences were statistically significant
      at 30 and 60 min (P = 0.027 and 0.008), respectively. Ninety percent versus 93%
      of the patients in BD and BT groups, respectively, expressed good to excellent
      satisfaction with pain relief. CONCLUSION: Combination of bupivacaine wound
      infiltration and IV tramadol provided better quality pain relief.

PMID- 29378992
TI  - Learning transurethral resection of the prostate: A comparison of the weight of
      resected specimen to the weight of enucleated specimen in open prostatectomy.
AB  - BACKGROUND: Minimally invasive procedures in the surgical management of benign
      prostate enlargement (BPE) are of limited use in the resource-poor settings due
      to nonavailability of the requisite facilities and skills. It has been observed
      that teaching uroendoscopy inclusive of transurethral resection of the prostate
      (TURP) can be challenging in the resource-poor settings where the traditional
      master-apprentice (Halstedian) approach has remained the prevalent training
      technique. PATIENTS AND METHODS: We aimed in this retrospective study to assess
      completeness of resection in TURP by comparing the proportion of prostate tissue
      resected to the proportion enucleated in open retropubic prostatectomy (ORP). We
      included all BPE patients on urethral catheter managed in the first 18 months
      after Halstedian training in TURP. The analysis was done using SPSS(r) 20 and
      VassarStats(r) online software. RESULTS: Twenty patients' files for TURP and
      twenty-eight patients' files for ORP met the inclusion criteria. Patients in the
      2 treatment arms were similar in age (P = 0.22), body mass index (P = 0.45),
      proportion of prostate tissue extirpated (P = 0.38), and International Prostate
      Symptom Score 12-month postprocedure (P = 0.06). However, larger prostates were
      treated with ORP (P < 0.0005). The correlation of the weight of resected specimen
      to preoperative prostate volume (PV) (r = 0.78; P < 0.001) was similar to that of
      enucleated specimen to preoperative PV (r = 0.89; P < 0.001). Similarly, the
      proportion of extirpated specimen correlated positively with the preoperative PVs
      for both TURP (r = 0.23; P = 0.33) and ORP (r = 0.292; P = 0.13), with no
      evidence of any difference between the 2 correlation values (P = 0.84).
      CONCLUSION: With appropriate patient selection, especially as a newly trained
      Surgeon, resections in TURP are as complete as enucleations in ORP.

PMID- 29378993
TI  - Heat-cured acrylic resin versus light-activated resin: a patient, professional
      and technician-based evaluation of mandibular implant-supported overdentures.
AB  - CONTEXT: Although light-activated resins (Eclipse) have been reported to possess
      superior physical and mechanical properties compared with the heat-cured acrylic
      resins (Lucitone-199), a few studies have compared overdentures with a locator
      attachment constructed from heat-cured acrylic resins with those constructed from
      light-activated resins. AIMS: This clinical study was designed to compare the
      performance of a mandibular implant-supported overdenture constructed from a heat
      cured acrylic resin (Lucitone-199) with that of an overdenture constructed from a
      light-activated resin (Eclipse). MATERIALS AND METHODS: Ten participants received
      two identical mandibular implant-retained overdentures (Lucitone-199 and Eclipse)
      opposing one maxillary denture in a random order. Each mandibular overdenture was
      delivered and worn for 6 months, and two weeks of rest was advised between wears
      to minimize any carryover effects. Three questionnaires were devised. The first
      questionnaire (patient evaluation) focused on evaluating different aspects of the
      denture and overall satisfaction. The second questionnaire (professional dentist
      evaluation) was based on a clinical evaluation of soft tissues, complications,
      and the applied technique. The third questionnaire (technician evaluation)
      involved ranking the different manufacturing steps of the denture and overall
      preferences. The obtained data was statistically analyzed using an independent
      sample t-test and the Wilcoxon rank-sum test. RESULTS: The clinician and
      technician preferred the Eclipse dentures because of their technical aspects,
      whereas the patients preferred the Lucitone-199 dentures for their aesthetic
      properties. CONCLUSIONS: Implant-supported overdentures constructed from a heat
      cured acrylic resin showed superior aesthetics and had a better odor compared
      with those constructed from a light-cured resin.

PMID- 29378994
TI  - Evaluation and comparison of mineral trioxide aggregate and biodentine in primary
      tooth pulpotomy: Clinical and radiographic study.
AB  - OBJECTIVES: Pulpotomy is the common therapy for cariously exposed pulps in
      symptom-free primary molar teeth. For many years, researchers have searched for
      an ideal material that allows regeneration of the residual pulp. The purpose of
      this study was to evaluate the efficacy of mineral trioxide aggregate (MTA),
      Biodentine as a pulpotomy medicament in primary teeth, both clinically and
      radiographically. MATERIALS AND METHODS: A total of 25 children (50 human primary
      molar teeth) aged between 5 and 9 years were selected in this randomized clinical
      study. The patients were randomly assigned to receive the pulpotomy medicaments
      in either [Group 1]: MTA or [Group 2]: Biodentine. All pulpotomized teeth were
      restored with stainless steel crowns and evaluated clinically and radiologically
      at 1, 3, 6 and 12 months. Statistical analysis using Mann-Whitney U test and
      Fisher's exact test, and chi-square test was performed to determine the
      significant differences between the groups. RESULTS: Clinical and radiological
      success rates were 96 and 80% in Group 1 and 96 and 60% in Group 2, respectively.
      There were no significant differences between the groups (P > 0.05). The
      radiographic success rates decreased in the controls, but there were no
      significant differences. CONCLUSION: Biodentine showed similar clinical and
      radiographic results as MTA in the 12-month evaluation and can be safely used as
      a pulpotomy medicament.

PMID- 29378995
TI  - Evaluation of vertical marginal adaptation of provisional crowns by digital
      microscope.
AB  - OBJECTIVE: To investigate and compare the degree of vertical marginal discrepancy
      of four provisional crown materials by digital microscope. MATERIALS AND METHODS:
      A total of 100 provisional crowns were fabricated on standardized resin dies by
      direct technique of provisional fabrication, using four different provisional
      materials (n = 25): Provisionals Fabricated by Systemp(r) c and b II, ivoclar
      vivadent, Schaan, Liechtenstein (group A); ProtempTM Plus, 3M ESPE, Neuss,
      Germany (group B); Success CD, PROMEDICA, Neumunster, Germany (group C); and
      Trim(r) Plus, Bosworth Company, Illinois, USA (group D). The provisional crowns
      were finished, tried, and locked with a customized device under 15N of vertical
      axial force. The vertical marginal discrepancy between the crown margin and the
      resin die was measured in micrometers using digital microscope (KH-7700, Hirox
      USA, Inc., NJ, USA) at mid of buccal, lingual, mesial, and distal margin areas by
      a trained technician. RESULTS: The mean values obtained for each group were as
      follows: group A = 129.10 +/- 41.64, group B = 123.36 +/- 40.94, group C = 89.67
      +/- 25.34, and group D = 107.24 +/- 38.32. Assessment by post hoc Tukey's test at
      5% significance level showed a statistically significant difference (P < 0.05)
      between group C and group D with the other groups. Results of one-way ANOVA
      showed a statistically nonsignificant difference (P > 0.05) between the means of
      the four areas of measurement for each group. CONCLUSION: Marginal discrepancy of
      the group C (Success CD) was the lowest among the provisionals tested. The mean
      vertical marginal gap values for the materials tested were found to be with in
      the clinically acceptable range (<130 MUm).

PMID- 29378996
TI  - Cardiac Troponin T and creatine kinase MB fraction levels among patients with
      acute ischemic stroke in Nigeria.
AB  - BACKGROUND: Stroke has been a global burden, with increasing morbidity and
      mortality. Serum cardiac troponin t (cTnT) and creatine kinase (CK-MB) fraction
      are reported to be elevated in patients admitted with acute ischaemic stroke and
      high level of these biomarkers indicated more severe stroke and neurologic
      deficit in some of the patients. OBJECTIVE: To evaluate the serum levels cardiac
      troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in patients with acute
      ischaemic stroke and relate the analytes to severity of stroke. METHOD: Patients
      with clinical diagnosis of ischaemic stroke diagnosed, confirmed by brain
      Computerized Tomography scan and equal number of apparently healthy age and sex
      matched were recruited. Serum cardiac troponin t (cTnT) and creatine kinase MB
      fraction (CK-MB) were analysed using ELISA method and Stroke severity was
      determined using National Institute of Health Stroke Score (NIHSS). RESULTS: Mean
      serum cardiac troponin t (cTnT) and creatine kinase MB fraction (CK-MB) in stroke
      patients were found to be higher than age sex matched control (p<0.05). NIHS
      Score of 12.2 +/- 5.43 and 9.78 +/- 3.97 were observed in Patients with elevated
      and normal cTnT respectively (p=0.009) while NIHS Score were similar in patients
      with elevated and normal CK-MB (p = 0.772). CONCLUSION: The mean values of serum
      cTnT and CK-MB were higher in acute ischaemic stroke patients compared to
      controls. Serum cardiac Troponin t level may be a significant biomarker of the
      severity of stroke.

PMID- 29378997
TI  - Ultrasound guided percutaneous nephrostomy: Experience at ahmadu bello university
      teaching hospital, Zaria.
AB  - BACKGROUND: Obstructive uropathy is a common problem in urologic practice;
      temporary relief of obstruction in the upper tract poses a significant challenge.
      Ultrasound-guided percutaneous nephrostomy (PCN) is an option for upper tract
      drainage; compared to fluoroscopic guidance, it is readily available, affordable,
      and not associated with radiation exposure. We present our experience with
      ultrasound-guided PCN. PATIENTS AND METHODS: We studied all patients who had
      ultrasound-guided PCN in our center between January 2013 and January 2017.
      Information obtained included the patients' demographics, clinical details,
      primary pathology, indications, outcome, and complications within 30 days.
      Relevant data were extracted and analyzed using descriptive statistics. RESULTS:
      A total number of 35 PCNs were performed in 26 patients within the period of
      study. The median age was 44.5 years. There were 17 females and 9 males. About
      88.2% of the females had ureteric obstruction from advanced carcinoma of the
      cervix while the predominant cause of obstruction in the males was advanced
      carcinoma of the bladder. Kidney access under ultrasound guidance required well
      dilated collecting systems for success and ease of puncture. The most common
      complication was hematuria, which resolved within 24-48 h in all patients
      uneventfully. CONCLUSION: PCN is an important and common procedure for temporary
      relief of upper urinary tract obstruction. While fluoroscopic guidance provides
      superior image guidance, ultrasound guidance is comparatively reliable, albeit
      with a longer learning curve. Adequate training, careful patients selection, and
      patience are key to success.

PMID- 29378998
TI  - The efficacy of hyaluronic acid in postextraction sockets of impacted third
      molars: A pilot study.
AB  - OBJECTIVE: This study aims to evaluate the effectiveness of local hyaluronic acid
      (HA) administration to surgically remove impacted third molar sockets and measure
      pain, swelling, and trismus. MATERIALS AND METHODS: The study included a total of
      25 healthy patients aged 18-29 years with asymptomatic bilaterally impacted lower
      third molars. All cases have been performed under local anesthesia. In the study
      group, 0.8% HA (Gengigel(r)) was applied in the postextraction sockets of the
      right third molars and in the control group nothing was applied to the extraction
      sockets of the left third molars. Postoperative pain, trismus, and swelling were
      evaluated on the 1st, 3rd, and 7th postoperative days. RESULTS: No difference was
      determined between groups in facial swelling and maximum mouth opening. However,
      the amount of pain significantly reduced in HA groups according to visual analog
      scale (P = 0.001). CONCLUSION: The results of this study showed that HA can
      produce an analgesic action in postextraction sockets after surgical removal of
      impacted teeth and therefore it has a clinical benefit to reduce usage of
      nonsteroidal anti-inflammatory drugs after dentoalveolar surgery.

PMID- 29378999
TI  - Normative and subjective need for orthodontic treatment within different age
      groups in a population in Turkey.
AB  - OBJECTIVE: To evaluate and compare the normative and subjective need for
      orthodontic treatment within different age groups in Turkey. METHODS: One
      thousand and sixteen patients from seven different demographic regions of Turkey
      (Marmara, Black Sea, East Anatolia, Southeastern Anatolia, Mediterranean, Aegean,
      and Central Anatolia Region) (mean age +/- SD: 12.80 +/- 3.57 years) were
      randomly selected and divided into six age groups (7-8,9-10,11-12,13-14,15-16,
      and 17-18 year-olds) and categorized according to the dental health component
      (DHC) of the index for orthodontic treatment need (IOTN). Additionally, the
      patients were asked to indicate the photograph that was most similar to their own
      dentition from the 10-point scale of the aesthetic component of IOTN. RESULTS:
      The DHC of IOTN was not significantly different between the six age groups (P >
      0.05). However, no/slight need (aesthetic component 1-4) for orthodontic
      treatment according to AC of IOTN was significantly higher in 13-14,15-16, and 17
      18 age groups than 7-8, 9-10, and 11-12 age groups (P < 0.05). No sex differences
      were found in both DHC and aesthetic component of IOTN between age groups (P >
      0.05). CONCLUSION: The normative need distribution was homogeneous within all the
      age groups according to DHC. However, the subjective need for orthodontic
      treatment was higher in the younger age groups.

PMID- 29379000
TI  - Eyelash extension use among female students in a Tertiary Institution in Nigeria:
      A study of kaduna polytechnic, Kaduna.
AB  - BACKGROUND: Eyelash extensions involve the attachment of synthetic eyelashes made
      of chemical fibers or other materials onto natural eyelashes. It has become
      common practice among Nigerian women for various reasons. Aim/Objectives: The aim
      is to assess eyelash extension use among students of a higher institution in
      Nigeria, the reasons for its use and related eye complications. MATERIALS AND
      METHODS: This is a cross-sectional descriptive study using structured self
      administered questionnaire. Stratified sampling technique was used. The key items
      in the questionnaire were sociodemographic variables, knowledge and use of
      eyelashes extension, reasons for the use of eyelashes extension and eye
      symptoms/complications experienced during such use. A total of 310questionnaires
      were completely and correctly filled. The results were analyzed using SPSS
      version 23.0 statistical package. RESULTS: There were 310 respondents; the age
      range was 16-52 with a mean of 23.0 years +/- 4.8. The prevalence of eyelash use
      was 38.7%. Beauty was the most common reason for lash extension 56.1% (n = 174).
      Others were curiosity, peer pressure, and replacement therapy. The most common
      complication was itching 45.8% (n = 142). Others were redness, pain, heavy
      eyelids, loss of lashes, casting of shadow in vision, tearing, burning sensation,
      foreign body sensation, and boils (stye) on the eyelid. CONCLUSION: Eyelash
      extension use is popular among young female students of higher institutions
      commonly for esthetic reasons (often because they desire to become more
      beautiful). Majority of them experience one ocular symptom or the other.
      Attention should, therefore, be paid to the potential health risk of the
      procedure and its use should be made much safer for our women.

PMID- 29379001
TI  - Influence of blood contamination during multimode adhesive application on the
      microtensile bond strength to dentin.
AB  - OBJECTIVES: The present study evaluated the effects of blood contamination
      performed at different steps of bonding on the microtensile bond strength (MUTBS)
      of multimode adhesives to dentin when using the self-etch approach. MATERIALS AND
      METHODS: Seventy-five molars were randomly assigned to three adhesive groups
      comprising 25 specimens each: two multimode adhesives [Single Bond Universal
      (SBU) and All-Bond Universal (ABU)] and a conventional one-step self-etch
      adhesive [Clearfil S3 Bond Plus (CSBP)]. Each group was subdivided as follows:
      (1) uncontaminated (control): bonding application/light curing as a positive
      control; (2) contamination-1 (cont-1): bonding application/light curing/blood
      contamination/dry as a negative control; (3) contamination-2 (cont-2): bonding
      application/light curing/blood contamination/rinse/dry; (4) contamination-3 (cont
      3): bonding application/blood contamination/dry/bonding re-application/light
      curing; and (5) contamination-4 (cont-4): bonding application/blood
      contamination/rinse/dry/bonding re-application/light curing. Dentin specimens
      were prepared for MUTBS testing after the composite resin application. Data were
      analyzed with two-way ANOVA and post-hoc tests (alpha = 0.05). RESULTS: MUTBS
      values were similar in cont-3 groups, and ABU/cont-4 and corresponding control
      groups, but were significantly lower in the other groups than in their control
      groups (P < 0.05). Cont-1 groups showed the lowest MUTBS values (P < 0.05).
      CONCLUSIONS: Neither decontamination method prevented the decrease in MUTBS when
      contamination occurred after light curing. Drying the blood contaminants and
      reapplying the adhesive may regain the dentin adhesion when contamination occurs
      before light curing. Alternatively, rinsing and drying contaminants followed by
      adhesive re-application may be effective depending on adhesive type.

PMID- 29379002
TI  - Bilateral simultaneous macular infarction with spontaneous visual recovery in
      genotype ss hemoglobinopathy patient.
AB  - To report the rare and dramatic event of bilateral macular infarction in a sickle
      cell hemoglobinopathy (SS genotype) patient, resulting in bilateral severe
      reduction in visual acuity. Without any intervention, the patient's vision
      gradually improved over the follow-up period. Central visual field defects
      however persisted. A 21-year-old male Nigerian, presented with a 1-week history
      of bilateral sudden painless loss of vision. His symptom was associated with
      fever, feeling of heaviness in the chest and head, and a dizzy spell. Visual
      acuity was reduced to 20/200 in both eyes and near acuity was; right eye: N24,
      left eye: N36. Funduscopy showed a pale, milky white, thickened retinal patch
      superotemporal to the fovea in both eyes. Fluorescein Angiograph: revealed
      features consistent with occlusion of the parafoveal terminal arterioles in both
      eyes. Although he did not receive any ocular treatment, and exchange blood
      transfusion was not done, he regained near-normal visual acuity in both eyes over
      a 17-month follow-up period, central visual field defects persisted in both eyes.
      Visual recovery in this patient demonstrates that macular function could improve
      over time following macular ischemia, without any treatment. Patients and caring
      physicians should be aware of this possibility.

PMID- 29379003
TI  - Ligneous periodontitis in a child with plasminogen deficiency.
AB  - Ligneous periodontitis (LP), a rare periodontal disease, is seen secondary to
      plasminogen deficiency and fibrin deposition. It is characterized by nodular
      gingival enlargements and progressive destructive membranous periodontal disease.
      It generally ends with the early loss of teeth. Defective fibrinolysis and
      abnormal wound healing is the main pathogenesis of this rare disease and should
      be considered different from other mucosal systemic disorders. In this case
      report, we describe the management of ligneous periodontitis and ligneous
      conjunctivitis developing secondary to plasminogen deficiency in a 6-year-old
      girl.

PMID- 29379004
TI  - Pneumomediastinum and Pneumothorax Associated with Herpes Simplex Virus (HSV)
      Pneumonia.
AB  - BACKGROUND Pneumonia is one of the most common causes of death from infectious
      disease in the United States (US). Although most cases of community-acquired
      pneumonia (CAP) are secondary to bacterial infection, up to one-third of cases
      are secondary to viral infection, most commonly due to rhinovirus and influenza
      virus. Pneumonia due to herpes simplex virus (HSV) is rare, and there is limited
      knowledge of the pathogenesis and clinical complications. This report is of a
      fatal case of HSV pneumonia associated with bilateral pneumothorax and
      pneumomediastinum. CASE REPORT A 36-year-old homeless male Hispanic patient, who
      was a chronic smoker, with a history of intravenous drug abuse and a medical
      history of chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
      infection, not on highly active antiretroviral therapy (HAART), was admitted to
      hospital as an emergency with a seven-day history of productive purulent cough.
      The patient was admitted to the medical intensive care unit (MICU) with a
      diagnosis of CAP, with intubation and mechanical ventilation. Broncho-alveolar
      lavage (BAL) was performed and was positive for HSV. The patient developed
      bilateral pneumothorax with pneumomediastinum, which was fatal, despite
      aggressive clinical management. CONCLUSIONS Pneumonia due to HSV infection is
      uncommon but has a high mortality. Although HSV pneumonia has been described in
      immunocompromised patients, further studies are required to determine the
      pathogenesis, early detection, identification of patients who are at risk and to
      determine the most effective approaches to prophylaxis and treatment for HSV
      pneumonia.

PMID- 29379005
TI  - Association of Single-Nucleotide Polymorphisms of C-Reactive Protein Gene with
      Susceptibility to Infantile Sepsis in Southern China.
AB  - BACKGROUND C-reactive protein (CRP) is an important biomarker of sepsis. Several
      single-nucleotide polymorphisms (SNPs) in the CRP gene can determine plasma CRP
      levels and are risk factors in many diseases, such as cancer, arteritis, and
      diabetes. However, it is unknown whether polymorphisms in CRP are associated with
      susceptibility to and outcome of infantile sepsis. We explored the effect of
      these SNPs on CRP response in infantile sepsis, and compared genetic data on
      patients with sepsis. MATERIAL AND METHODS A total of 49 infants with sepsis and
      20 healthy infants were enrolled during hospitalization, and 3 SNPs in the CRP
      gene region (rs1205, rs2808530, and rs3091244) were genotyped and then analyzed
      for associations with CRP levels and sepsis. RESULTS The CRP means concentration
      results showed that mean CRP concentration was different in the 4 groups
      (healthy, sepsis, severe sepsis, and septic shock) and was positively correlated
      with the severity of infantile sepsis. There was also a difference in CRP SNP
      rs1205 between infants with septic shock and healthy infants, and between infants
      with septic shock and infants with sepsis. No differences were observed in SNP
      rs2808630 and SNP rs3091244. CONCLUSIONS Our study suggests that rs1205 genetic
      variability in the CRP gene determines the CRP levels in sepsis of different
      severities, while SNP rs3091244 and SNP rs2808630 are not associated with sepsis.
      However, the results of the present study on SNP rs1205, rs3091244, and rs2808630
      in the CRP gene should be interpreted with caution due to limited sample size and
      sample heterogeneity. Large-scale, well-designed studies are needed to validate
      our findings.

PMID- 29379006
TI  - Long-Term Outcomes of Ante-Situm Resection and Auto-Transplantation in
      Conventionally Unresectable Hepatocellular Carcinoma: A Single-Center Experience.
AB  - BACKGROUND Ante-situm resection and auto-transplantation (ante-situm for short)
      provides a more aggressive approach to conventionally unresectable hepatocellular
      carcinoma (HCC). We described the long-term outcomes of patients with HCCs who
      underwent this technique. MATERIAL AND METHODS Between October 2005 and December
      2016, we performed 23 ante-situm liver resections. We evaluated postoperative
      complications, 90-day mortality, recurrence, and long-term survival rates, and
      reviewed the literature on this topic. RESULTS Five types of complications
      associated with six patients were observed.: 1) primary nonfunctioning liver,
      thus receiving a liver transplantation; 2) initial poor liver function with
      recovery two weeks after treatment; 3) diagnoses of portal vein tumor thrombosis,
      biliary fistula, and small-for-size syndrome, respectively. The median follow-up
      was 3.6 years; 12 out of 23 patients were alive at the end of the study. One
      patient who had hepatic recurrence was lost to follow-up after three months. One
      patient died of multiple organ dysfunction syndrome after the operation, nine
      patients died due to hepatic recurrence and/or extrahepatic metastasis of HCC.
      The one-year, three-year, five-year, and 10-year survival rates were 65.2%,
      56.5%, 50.9%, and 20.3%, respectively. The one-year, three-year, five-year, and
      10-year recurrence rates were 60.9%, 50.7%, 50.7%, and 50.7%, respectively. The
      chi-square test revealed the patients with recurrence after ante-situm technique
      were more likely to have poor prognosis (mortality of patients with recurrence
      versus no-recurrence: 88.9% versus 14.3%, p<0.05) and a strong association was
      evidenced by Cramer's V statistic (Cramer's V=0.734). CONCLUSIONS Ante-situm
      procedure showed benefits in select patients with HCCs who had contraindications
      for conventional resection operations. In our case series, the ante-situm
      technique resulted in lower mortality compared to other ex-vivo hepatic resection
      techniques reported in the literature and similar long-term efficacy compared to
      cases of HCCs suitable for conventional resections. HCCs recurrence was a major
      risk factor associated with the survival rate of ante-situm technique.

PMID- 29379007
TI  - Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal
      amino alcohols.
AB  - Enantiopure vicinal amino alcohols and derivatives are essential structural
      motifs in natural products and pharmaceutically active molecules, and serve as
      main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic
      protocols for this class of compounds are still rare and often suffer from
      limited scope of substrates, relatively low regio- or stereoselectivities, thus
      prompting the development of more effective methodologies. Herein we report a
      dual catalytic strategy for the convergent enantioselective synthesis of vicinal
      amino alcohols. The method features a radical-type Zimmerman-Traxler transition
      state formed from a rare earth metal with a nitrone and an aromatic ketyl radical
      in the presence of chiral N,N'-dioxide ligands. In addition to high level of
      enantio- and diastereoselectivities, our synthetic protocol affords advantages of
      simple operation, mild conditions, high-yielding, and a broad scope of
      substrates. Furthermore, this protocol has been successfully applied to the
      concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and
      selegiline).

PMID- 29379008
TI  - An artificial nociceptor based on a diffusive memristor.
AB  - A nociceptor is a critical and special receptor of a sensory neuron that is able
      to detect noxious stimulus and provide a rapid warning to the central nervous
      system to start the motor response in the human body and humanoid robotics. It
      differs from other common sensory receptors with its key features and functions,
      including the "no adaptation" and "sensitization" phenomena. In this study, we
      propose and experimentally demonstrate an artificial nociceptor based on a
      diffusive memristor with critical dynamics for the first time. Using this
      artificial nociceptor, we further built an artificial sensory alarm system to
      experimentally demonstrate the feasibility and simplicity of integrating such
      novel artificial nociceptor devices in artificial intelligence systems, such as
      humanoid robots.

PMID- 29379009
TI  - The SAM domain of mouse SAMHD1 is critical for its activation and regulation.
AB  - Human SAMHD1 (hSAMHD1) is a retroviral restriction factor that blocks HIV-1
      infection by depleting the cellular nucleotides required for viral reverse
      transcription. SAMHD1 is allosterically activated by nucleotides that induce
      assembly of the active tetramer. Although the catalytic core of hSAMHD1 has been
      studied extensively, previous structures have not captured the regulatory SAM
      domain. Here we report the crystal structure of full-length SAMHD1 by capturing
      mouse SAMHD1 (mSAMHD1) structures in three different nucleotide bound states.
      Although mSAMHD1 and hSAMHD1 are highly similar in sequence and function, we find
      that mSAMHD1 possesses a more complex nucleotide-induced activation process,
      highlighting the regulatory role of the SAM domain. Our results provide insights
      into the regulation of SAMHD1 activity, thereby facilitating the improvement of
      HIV mouse models and the development of new therapies for certain cancers and
      autoimmune diseases.

PMID- 29379010
TI  - Isoliquiritigenin blunts osteoarthritis by inhibition of bone resorption and
      angiogenesis in subchondral bone.
AB  - Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been
      demonstrated to exert attenuation of osteoclastogenesis and anti-angiogenesis
      activity in a wide variety of cells. Here, we first evaluated the effects of ISL
      on pathogenesis of osteoarthritis in a mouse model of OA. The data showed that
      ISL blunted progression of OA and lowered the Osteoarthritis Research Society
      International (OARSI)-Modified Making Score and protected the articular
      cartilage. The thickness of calcified cartilage zone was significantly decreased
      in ISL-treated ACLT mice compared with vehicle group. ISL increased expression
      level of lubricin and decreased collagen X (Col X), matrix metalloproteinase-13
      (MMP-13). Moreover, ISL reduced aberrant active subchondral bone remodelling,
      including lowered trabecular pattern factor (Tb.pf) and increased bone
      volume/tissue volume (BV/TV, %) and thickness of subchondral bone plate (SBP)
      compared with vehicle-treated group. The results of immunostaining further
      revealed that ISL directly reduced RANKL-RANK-TRAF6 singling pathway induced
      osteoclastogenesis, prevented abnormal bone formation through indirect inhibition
      of TGF-beta release. Additionally, ISL exerts anti-angiogenesis effects in
      subchondral bone through direct suppression of MMP-2. These results indicated
      that ISL attenuates progression of OA by inhibition of bone resorption and
      angiogenesis in subchondral bone, indicating that this may be a potential
      preventive therapy for OA.

PMID- 29379012
TI  - Antimicrobial activity of apple cider vinegar against Escherichia coli,
      Staphylococcus aureus and Candida albicans; downregulating cytokine and microbial
      protein expression.
AB  - The global escalation in antibiotic resistance cases means alternative
      antimicrobials are essential. The aim of this study was to investigate the
      antimicrobial capacity of apple cider vinegar (ACV) against E. coli, S. aureus
      and C. albicans. The minimum dilution of ACV required for growth inhibition
      varied for each microbial species. For C. albicans, a 1/2 ACV had the strongest
      effect, S. aureus, a 1/25 dilution ACV was required, whereas for E-coli cultures,
      a 1/50 ACV dilution was required (p < 0.05). Monocyte co-culture with microbes
      alongside ACV resulted in dose dependent downregulation of inflammatory cytokines
      (TNFalpha, IL-6). Results are expressed as percentage decreases in cytokine
      secretion comparing ACV treated with non-ACV treated monocytes cultured with E
      coli (TNFalpha, 99.2%; IL-6, 98%), S. aureus (TNFalpha, 90%; IL-6, 83%) and C.
      albicans (TNFalpha, 83.3%; IL-6, 90.1%) respectively. Proteomic analyses of
      microbes demonstrated that ACV impaired cell integrity, organelles and protein
      expression. ACV treatment resulted in an absence in expression of DNA starvation
      protein, citrate synthase, isocitrate and malate dehydrogenases in E-coli;
      chaperone protein DNak and ftsz in S. aureus and pyruvate kinase, 6
      phosphogluconate dehydrogenase, fructose bisphosphate were among the enzymes
      absent in C.albican cultures. The results demonstrate ACV has multiple
      antimicrobial potential with clinical therapeutic implications.

PMID- 29379011
TI  - Streamlined ex vivo and in vivo genome editing in mouse embryos using recombinant
      adeno-associated viruses.
AB  - Recent advances using CRISPR-Cas9 approaches have dramatically enhanced the ease
      for genetic manipulation in rodents. Notwithstanding, the methods to deliver
      nucleic acids into pre-implantation embryos have hardly changed since the
      original description of mouse transgenesis more than 30 years ago. Here we report
      a novel strategy to generate genetically modified mice by transduction of CRISPR
      Cas9 components into pre-implantation mouse embryos via recombinant adeno
      associated viruses (rAAVs). Using this approach, we efficiently generated a
      variety of targeted mutations in explanted embryos, including indel events
      produced by non-homologous end joining and tailored mutations using homology
      directed repair. We also achieved gene modification in vivo by direct delivery of
      rAAV particles into the oviduct of pregnant females. Our approach greatly
      simplifies the generation of genetically modified mice and, more importantly,
      opens the door for streamlined gene editing in other mammalian species.

PMID- 29379013
TI  - Effects of Distal Mutations on the Structure, Dynamics and Catalysis of Human
      Monoacylglycerol Lipase.
AB  - An understanding of how conformational dynamics modulates function and catalysis
      of human monoacylglycerol lipase (hMGL), an important pharmaceutical target, can
      facilitate the development of novel ligands with potential therapeutic value.
      Here, we report the discovery and characterization of an allosteric, regulatory
      hMGL site comprised of residues Trp-289 and Leu-232 that reside over 18 A away
      from the catalytic triad. These residues were identified as critical mediators of
      long-range communication and as important contributors to the integrity of the
      hMGL structure. Nonconservative replacements of Trp-289 or Leu-232 triggered
      concerted motions of structurally distinct regions with a significant
      conformational shift toward inactive states and dramatic loss in catalytic
      efficiency of the enzyme. Using a multimethod approach, we show that the
      dynamically relevant Trp-289 and Leu-232 residues serve as communication hubs
      within an allosteric protein network that controls signal propagation to the
      active site, and thus, regulates active-inactive interconversion of hMGL. Our
      findings provide new insights into the mechanism of allosteric regulation of
      lipase activity, in general, and may provide alternative drug design
      possibilities.

PMID- 29379014
TI  - Long-term graft function following autologous hematopoietic cell transplantation
      and the impact of preemptive plerixafor in predicted poor mobilizers.

PMID- 29379015
TI  - Membrane bending occurs at all stages of clathrin-coat assembly and defines
      endocytic dynamics.
AB  - Clathrin-mediated endocytosis (CME) internalizes plasma membrane by reshaping
      small regions of the cell surface into spherical vesicles. The key mechanistic
      question of how coat assembly produces membrane curvature has been studied with
      molecular and cellular structural biology approaches, without direct
      visualization of the process in living cells; resulting in two competing models
      for membrane bending. Here we use polarized total internal reflection
      fluorescence microscopy (pol-TIRF) combined with electron, atomic force, and
      super-resolution optical microscopy to measure membrane curvature during CME.
      Surprisingly, coat assembly accommodates membrane bending concurrent with or
      after the assembly of the clathrin lattice. Once curvature began, CME proceeded
      to scission with robust timing. Four color pol-TIRF showed that CALM accumulated
      at high levels during membrane bending, implicating its auxiliary role in
      curvature generation. We conclude that clathrin-coat assembly is versatile and
      that multiple membrane-bending trajectories likely reflect the energetics of coat
      assembly relative to competing forces.

PMID- 29379016
TI  - Large magneto-thermopower in MnGe with topological spin texture.
AB  - Quantum states characterized by nontrivial topology produce interesting
      electrodynamics and versatile electronic functionalities. One source for such
      remarkable phenomena is emergent electromagnetic field, which is the outcome of
      interplay between topological spin structures with scalar spin chirality and
      conduction electrons. However, it has scarcely been exploited for emergent
      function related to heat-electricity conversion. Here we report an unusually
      enhanced thermopower by application of magnetic field in MnGe hosting topological
      spin textures. By considering all conceivable origins through quantitative
      investigations of electronic structures and properties, a possible origin of
      large magneto-thermopower is assigned to the strong energy dependence of charge
      transport lifetime caused by unconventional carrier scattering via the dynamics
      of emergent magnetic field. Furthermore, high-magnetic-field measurements
      corroborate the presence of residual magnetic fluctuations even in the nominally
      ferromagnetic region, leading to a subsisting behavior of field-enhanced
      thermopower. The present finding may pave a way for thermoelectric function of
      topological magnets.

PMID- 29379018
TI  - Anderson localization of a one-dimensional quantum walker.
AB  - We study the evolution of a system performing a one-dimensional quantum walk in
      the presence of static phase disorder. The same model also describes the
      propagation of classical light pulses in photonic mesh lattices. We study the
      interplay between the coupling (i.e. the bias of the "quantum coin") and
      disorder. We provide an exact analytical expression for the localization length
      for two limiting cases of strong and weak phase disorder. In all the cases of
      interest we supply numerical simulations for participation ratio, Lyapunov
      exponent and the return probability as functions of the coupling parameter.

PMID- 29379017
TI  - Hotspots of dendritic spine turnover facilitate clustered spine addition and
      learning and memory.
AB  - Modeling studies suggest that clustered structural plasticity of dendritic spines
      is an efficient mechanism of information storage in cortical circuits. However,
      why new clustered spines occur in specific locations and how their formation
      relates to learning and memory (L&M) remain unclear. Using in vivo two-photon
      microscopy, we track spine dynamics in retrosplenial cortex before, during, and
      after two forms of episodic-like learning and find that spine turnover before
      learning predicts future L&M performance, as well as the localization and rates
      of spine clustering. Consistent with the idea that these measures are causally
      related, a genetic manipulation that enhances spine turnover also enhances both
      L&M and spine clustering. Biophysically inspired modeling suggests turnover
      increases clustering, network sparsity, and memory capacity. These results
      support a hotspot model where spine turnover is the driver for localization of
      clustered spine formation, which serves to modulate network function, thus
      influencing storage capacity and L&M.

PMID- 29379019
TI  - One-stage technique for sagittal split ramus osteotomy combined with mandibular
      angle ostectomy.
AB  - Bilateral sagittal split ramus osteotomy (BSSRO) is commonly used to correct
      mandibular prognathism or retrognathism. Patients with mandibular prognathism or
      retrognathism may also present with a prominent mandibular angle. In this paper,
      we share our experience on BSSRO with mandibular angle resection. Eleven patients
      who were treated from July 2014 to December 2016 were included in this study. The
      mandibular angle was resected through the medial side of the mandible after
      BSSRO. The mandibular angle measurements of the patients changed significantly
      after surgery (p < 0.05). Unanticipated fractures and mandibular hematoma did not
      occur. Therefore, BSSRO combined with mandibular angle ostectomy through the
      medial side of the mandible can be used to safely and effectively correct facial
      deformity.

PMID- 29379020
TI  - Molecular basis for the specific and multivariant recognitions of RNA substrates
      by human hnRNP A2/B1.
AB  - Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many
      biological processes, including maturation, transport, and metabolism of mRNA,
      and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control
      the microRNAs sorting to exosomes and promote primary microRNA processing as a
      potential m6A "reader." hnRNP A2/B1 contains two RNA recognition motifs that
      provide sequence-specific recognition of RNA substrates. Here, we determine
      crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various
      RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1
      and RRM2 domains, respectively. Further structural and biochemical results
      demonstrate multivariant binding modes for sequence-diversified RNA substrates,
      supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our
      studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may
      mediate effects of m6A through a "m6A switch" mechanism, instead of acting as a
      direct "reader" of m6A modification.

PMID- 29379021
TI  - Dual-band Circular Polarizer Based on Simultaneous Anisotropy and Chirality in
      Planar Metamaterial.
AB  - Metamaterial of dual-square array is proposed to design a dual-band circular
      polarizer. The novel design of asymmetric unit cell and layout of duplicate
      arrays significantly enhances the coupling between electric and magnetic fields.
      Simulation and measurement results show that the polarizer presents wide angle
      circular dichroism and circular birefringence. Moreover, the polarization
      conversion of the proposed metamaterial changes with frequency, incident angle,
      and polarization of incident waves. The fundamental mechanism behind is concluded
      to be the angle-dependent chirality and dispersion of our novel design.

PMID- 29379022
TI  - Fused electron deficient semiconducting polymers for air stable electron
      transport.
AB  - Conventional semiconducting polymer synthesis typically involves transition metal
      mediated coupling reactions that link aromatic units with single bonds along the
      backbone. Rotation around these bonds contributes to conformational and energetic
      disorder and therefore potentially limits charge delocalisation, whereas the use
      of transition metals presents difficulties for sustainability and application in
      biological environments. Here we show that a simple aldol condensation reaction
      can prepare polymers where double bonds lock-in a rigid backbone conformation,
      thus eliminating free rotation along the conjugated backbone. This polymerisation
      route requires neither organometallic monomers nor transition metal catalysts and
      offers a reliable design strategy to facilitate delocalisation of frontier
      molecular orbitals, elimination of energetic disorder arising from rotational
      torsion and allowing closer interchain electronic coupling. These characteristics
      are desirable for high charge carrier mobilities. Our polymers with a high
      electron affinity display long wavelength NIR absorption with air stable electron
      transport in solution processed organic thin film transistors.

PMID- 29379023
TI  - Competition between electron pairing and phase coherence in superconducting
      interfaces.
AB  - In LaAlO3/SrTiO3 heterostructures, a gate tunable superconducting electron gas is
      confined in a quantum well at the interface between two insulating oxides.
      Remarkably, the gas coexists with both magnetism and strong Rashba spin-orbit
      coupling. However, both the origin of superconductivity and the nature of the
      transition to the normal state over the whole doping range remain elusive. Here
      we use resonant microwave transport to extract the superfluid stiffness and the
      superconducting gap energy of the LaAlO3/SrTiO3 interface as a function of
      carrier density. We show that the superconducting phase diagram of this system is
      controlled by the competition between electron pairing and phase coherence. The
      analysis of the superfluid density reveals that only a very small fraction of the
      electrons condenses into the superconducting state. We propose that this
      corresponds to the weak filling of high-energy dxz/dyz bands in the quantum well,
      more apt to host superconductivity.

PMID- 29379024
TI  - Isolated proton bunch acceleration by a petawatt laser pulse.
AB  - Often, the interpretation of experiments concerning the manipulation of the
      energy distribution of laser-accelerated ion bunches is complicated by the
      multitude of competing dynamic processes simultaneously contributing to recorded
      ion signals. Here we demonstrate experimentally the acceleration of a clean
      proton bunch. This was achieved with a microscopic and three-dimensionally
      confined near critical density plasma, which evolves from a 1 um diameter plastic
      sphere, which is levitated and positioned with micrometer precision in the focus
      of a Petawatt laser pulse. The emitted proton bunch is reproducibly observed with
      central energies between 20 and 40 MeV and narrow energy spread (down to 25%)
      showing almost no low-energetic background. Together with three-dimensional
      particle-in-cell simulations we track the complete acceleration process,
      evidencing the transition from organized acceleration to Coulomb repulsion. This
      reveals limitations of current high power lasers and viable paths to optimize
      laser-driven ion sources.

PMID- 29379025
TI  - Shape evolution of ooids: a geometric model.
AB  - Striking shapes in nature have been documented to result from chemical
      precipitation - such as terraced hot springs and stromatolites - which often
      proceeds via surface-normal growth. Another studied class of objects is those
      whose shape evolves by physical abrasion - the primary example being river and
      beach pebbles - which results in shape-dependent surface erosion. While shapes
      may evolve in a self-similar manner, in neither growth nor erosion can a surface
      remain invariant. Here we investigate a rare and beautiful geophysical problem
      that combines both of these processes; the shape evolution of carbonate particles
      known as ooids. We hypothesize that mineral precipitation, and erosion due to
      wave-current transport, compete to give rise to novel and invariant geometric
      forms. We show that a planar (2D) mathematical model built on this premise
      predicts time-invariant (equilibrium) shapes that result from a balance between
      precipitation and abrasion. These model results produce nontrivial shapes that
      are consistent with mature ooids found in nature.

PMID- 29379026
TI  - Adhesive Leaf Created by a Corona Discharge.
AB  - Here, we report a new concept of both the adhesive manner and material, named
      "adhesive leaf (AL)," based on the leaf of the plant Heteropanax fragrans. The
      treatment of the corona discharge on the leaf surface can cause the nano
      /microdestruction of the leaf epidermis, resulting in an outward release of sap.
      The glucose-containing sap provided the AL with a unique ability to stick to
      various substrates such as steel, polypropylene, and glass. Moreover, we reveal
      that the AL adhesion strength depends on the AL size, as well as the corona
      discharge intensity. Conventional adhesives, such as glue and bond, lose their
      adhesive property and leave dirty residues upon the removal of the attached
      material. Unlike the conventional methods, the AL is advantageous as it can be
      repeatedly attached and detached thoroughly until the sap liquid is exhausted;
      its adhesive ability is maintained for at least three weeks at room temperature.
      Our findings shed light on a new concept of a biodegradable adhesive material
      that is created by a simple surface treatment.

PMID- 29379027
TI  - Nitrogen Fertilization Elevated Spatial Heterogeneity of Soil Microbial Biomass
      Carbon and Nitrogen in Switchgrass and Gamagrass Croplands.
AB  - The effects of intensive nitrogen (N) fertilizations on spatial distributions of
      soil microbes in bioenergy croplands remain unknown. To quantify N fertilization
      effect on spatial heterogeneity of soil microbial biomass carbon (MBC) and N
      (MBN), we sampled top mineral horizon soils (0-15 cm) using a spatially explicit
      design within two 15-m2 plots under three fertilization treatments in two
      bioenergy croplands in a three-year long fertilization experiment in Middle
      Tennessee, USA. The three fertilization treatments were no N input (NN), low N
      input (LN: 84 kg N ha-1 in urea) and high N input (HN: 168 kg N ha-1 in urea).
      The two crops were switchgrass (SG: Panicum virgatum L.) and gamagrass (GG:
      Tripsacum dactyloides L.). Results showed that N fertilizations little altered
      central tendencies of microbial variables but relative to LN, HN significantly
      increased MBC and MBC:MBN (GG only). HN possessed the greatest within-plot
      variances except for MBN (GG only). Spatial patterns were generally evident under
      HN and LN plots and much less so under NN plots. Substantially contrasting
      spatial variations were also identified between croplands (GG > SG) and among
      variables (MBN, MBC:MBN > MBC). This study demonstrated that spatial
      heterogeneity is elevated in microbial biomass of fertilized soils likely by
      uneven fertilizer application in bioenergy crops.

PMID- 29379028
TI  - An evolutionary NS1 mutation enhances Zika virus evasion of host interferon
      induction.
AB  - Virus-host interactions determine an infection outcome. The Asian lineage of Zika
      virus (ZIKV), responsible for the recent epidemics, has fixed a mutation in the
      NS1 gene after 2012 that enhances mosquito infection. Here we report that the
      same mutation confers NS1 to inhibit interferon-beta induction. This mutation
      enables NS1 binding to TBK1 and reduces TBK1 phosphorylation. Engineering the
      mutation into a pre-epidemic ZIKV strain debilitates the virus for interferon
      beta induction; reversing the mutation in an epidemic ZIKV strain invigorates the
      virus for interferon-beta induction; these mutational effects are lost in IRF3
      knockout cells. Additionally, ZIKV NS2A, NS2B, NS4A, NS4B, and NS5 can also
      suppress interferon-beta production through targeting distinct components of the
      RIG-I pathway; however, for these proteins, no antagonistic difference is
      observed among various ZIKV strains. Our results support the mechanism that ZIKV
      has accumulated mutation(s) that increases the ability to evade immune response
      and potentiates infection and epidemics.

PMID- 29379029
TI  - Molecular engineering of antibodies for site-specific covalent conjugation using
      CRISPR/Cas9.
AB  - Site-specific modification of antibodies has become a critical aspect in the
      development of next-generation immunoconjugates meeting criteria of clinically
      acceptable homogeneity, reproducibility, efficacy, ease of manufacturability, and
      cost-effectiveness. Using CRISPR/Cas9 genomic editing, we developed a simple and
      novel approach to produce site-specifically modified antibodies. A sortase tag
      was genetically incorporated into the C-terminal end of the third immunoglobulin
      heavy chain constant region (CH3) within a hybridoma cell line to manufacture
      antibodies capable of site-specific conjugation. This enabled an effective
      enzymatic site-controlled conjugation of fluorescent and radioactive cargoes to a
      genetically tagged mAb without impairment of antigen binding activity. After
      injection in mice, these immunoconjugates showed almost doubled specific
      targeting in the lung vs. chemically conjugated maternal mAb, and concomitant
      reduction in uptake in the liver and spleen. The approach outlined in this work
      provides a facile method for the development of more homogeneous, reproducible,
      effective, and scalable antibody conjugates for use as therapeutic and diagnostic
      tools.

PMID- 29379030
TI  - SPK1-transfected UCMSC has better therapeutic activity than UCMSC in the
      treatment of experimental autoimmune encephalomyelitis model of Multiple
      sclerosis.
AB  - Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the
      central nervous system that leads to chronic demyelination with axonal damage and
      neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic
      approach for MS. In the current study, we investigated the effects of MSCs
      derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1
      (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified
      by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of
      the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by
      reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1
      transplantation also could inhibit the development of natural killer (NK)
      responses in the spleen of EAE mice, and increase the ratio of CD4+ CD25+ FoxP3+
      (Treg) T cells. Furthermore, we described that a shift in the cytokine response
      from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS
      autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for
      the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.

PMID- 29379031
TI  - Microbial fuel cell assisted band gap narrowed TiO2 for visible light-induced
      photocatalytic activities and power generation.
AB  - This paper reports a simple, biogenic and green approach to obtain narrow band
      gap and visible light-active TiO2 nanoparticles. Commercial white TiO2 (w-TiO2)
      was treated in the cathode chamber of a Microbial Fuel Cell (MFC), which produced
      modified light gray TiO2 (g-TiO2) nanoparticles. The DRS, PL, XRD, EPR, HR-TEM,
      and XPS were performed to understand the band gap decline of g-TiO2. The optical
      study revealed a significant decrease in the band gap of the g-TiO2 (E g  = 2.80
      eV) compared to the w-TiO2 (E g  = 3.10 eV). The XPS revealed variations in the
      surface states, composition, Ti4+ to Ti3+ ratio, and oxygen vacancies in the g
      TiO2. The Ti3+ and oxygen vacancy-induced enhanced visible light photocatalytic
      activity of g-TiO2 was confirmed by degrading different model dyes. The enhanced
      photoelectrochemical response under visible light irradiation further supported
      the improved performance of the g-TiO2 owing to a decrease in the electron
      transfer resistance and an increase in charge transfer rate. During the TiO2
      treatment process, electricity generation in MFC was also observed, which was
      ~0.3979 V corresponding to a power density of 70.39 mW/m2. This study confirms
      narrow band gap TiO2 can be easily obtained and used effectively as
      photocatalysts and photoelectrode material.

PMID- 29379032
TI  - Time Course of Cultural Differences in Spatial Frequency Use for Face
      Identification.
AB  - Several previous studies of eye movements have put forward that, during face
      recognition, Easterners spread their attention across a greater part of their
      visual field than Westerners. Recently, we found that culture's effect on the
      perception of faces reaches mechanisms deeper than eye movements, therefore
      affecting the very nature of information sampled by the visual system: that is,
      Westerners globally rely more than Easterners on fine-grained visual information
      (i.e. high spatial frequencies; SFs), whereas Easterners rely more on coarse
      grained visual information (i.e. low SFs). These findings suggest that culture
      influences basic visual processes; however, the temporal onset and dynamics of
      these culture-specific perceptual differences are still unknown. Here, we
      investigate the time course of SF use in Western Caucasian (Canadian) and East
      Asian (Chinese) observers during a face identification task. Firstly, our results
      confirm that Easterners use relatively lower SFs than Westerners, while the
      latter use relatively higher SFs. More importantly, our results indicate that
      these differences arise as early as 34 ms after stimulus onset, and remain stable
      through time. Our research supports the hypothesis that Westerners and Easterners
      initially rely on different types of visual information during face processing.

PMID- 29379033
TI  - Mechanisms driving the antibacterial and antibiofilm properties of Hp1404 and its
      analogue peptides against multidrug-resistant Pseudomonas aeruginosa.
AB  - Hp1404, identified from the venom of the scorpion Heterometrus petersii, displays
      antimicrobial activity with cytotoxicity. Several synthetic peptides were
      designed based on the parent peptide Hp1404 to reduce cytotoxicity and improve
      activity (deletion of glycine and phenylalanine, substitution with leucine and
      lysine). The analogue peptides generated comprised 12 amino acids and displayed
      amphipathic alpha-helical structures, with higher hydrophobic moments and net
      positive charge than those of the Hp1404. The analogues showed less hemolytic and
      toxic effects toward mammalian cells than the Hp1404, especially Hp1404-T1e,
      which exhibited particularly potent antibacterial and antibiofilm activities
      against multidrug-resistant Pseudomonas aeruginosa (MRPA) strains. The analogue
      peptide Hp1404-T1e was more stable against salt and trypsin than the Hp1404.
      Hp1404's mechanism of action involves binding to lipopolysaccharide (LPS),
      thereby killing bacteria through membrane disruption. Hp1404-T1e kills bacteria
      more rapidly than Hp1404 and not only seems to bind more strongly to LPS but may
      also be able to enter bacterial cells and interact with their DNA. Additionally,
      Hp1404-T1e can effectively kill bacteria in vivo. The results of this study
      indicate that Hp1404-T1e not only displays antimicrobial activity, but is also
      functional in physiological conditions, confirming its potential use as an
      effective therapeutic agent against MRPA.

PMID- 29379034
TI  - 3',4'-dihydroxyflavonol ameliorates endoplasmic reticulum stress-induced
      apoptosis and endothelial dysfunction in mice.
AB  - Endoplasmic reticulum (ER) stress has been implicated in the development of
      hypertension 3 through the induction of endothelial impairment. As 3',4'
      dihydroxyflavonol (DiOHF) 4 reduces vascular injury caused by
      ischaemia/reperfusion or diabetes, and flavonols have been demonstrated to
      attenuate ER stress, we investigated whether DiOHF can protect mice from ER
      stress-induced endothelial dysfunction. Male C57BLK/6 J mice were injected with
      tunicamycin to induce ER stress in the presence or absence of either DiOHF or
      tauroursodeoxycholic acid (TUDCA), an inhibitor of ER stress. Tunicamycin
      elevated blood pressure and impaired endothelium-dependent relaxation. Moreover,
      in aortae there was evidence of ER stress, oxidative stress and reduced NO
      production. This was coincident with increased NOX2 expression and reduced
      phosphorylation of endothelial nitric oxide synthase (eNOS) on Ser1176.
      Importantly, the effects of tunicamycin were significantly ameliorated by DiOHF
      or TUDCA. DiOHF also inhibited tunicamycin-induced ER stress and apoptosis in
      cultured human endothelial cells (HUVEC). These results provide evidence that ER
      stress is likely an important initiator of endothelial dysfunction through the
      induction of oxidative stress and a reduction in NO synthesis and that DiOHF
      directly protects against ER stress- induced injury. DiOHF may be useful to
      prevent ER and oxidative stress to preserve endothelial function, for example in
      hypertension.

PMID- 29379035
TI  - Distinctive expression of T cell guiding molecules in human autoimmune lymph node
      stromal cells upon TLR3 triggering.
AB  - Infections are implicated in autoimmunity. Autoantibodies are produced in
      lymphoid tissue where lymph node stromal cells (LNSCs) regulate lymphocyte
      function. Infections can alter the interaction between LNSCs and lymphocytes
      resulting in defective immune responses. In rheumatoid arthritis (RA)
      autoantibody production precedes clinical disease allowing identification of at
      risk individuals. We investigated the ability of human LNSCs derived from RA, RA
      risk and healthy individuals to sense and respond to pathogens. Human LNSCs
      cultured directly from freshly collected lymph node biopsies expressed TLR1-9
      with exception of TLR7. In all donors TLR3 triggering induced expression of ISGs,
      IL-6 and adhesion molecules like VCAM-1 and ICAM-1. Strikingly, T cell guiding
      chemokines CCL19 and IL-8 as well as the antiviral gene MxA were less induced
      upon TLR3 triggering in autoimmune LNSCs. This observed decrease, found already
      in LNSCs of RA-risk individuals, may lead to incorrect positioning of lymphocytes
      and aberrant immune responses during viral infections.

PMID- 29379036
TI  - Optophysiological Characterisation of Inner Retina Responses with High-Resolution
      Optical Coherence Tomography.
AB  - Low coherence laser interferometry has revolutionised quantitative biomedical
      imaging of optically transparent structures at cellular resolutions. We report
      the first optical recording of neuronal excitation at cellular resolution in the
      inner retina by quantifying optically recorded stimulus-evoked responses from the
      retinal ganglion cell layer and comparing them with an electrophysiological
      standard. We imaged anaesthetised paralysed tree shrews, gated image acquisition,
      and used numerical filters to eliminate noise arising from retinal movements
      during respiratory and cardiac cycles. We observed increases in contrast
      variability in the retinal ganglion cell layer and nerve fibre layer with flash
      stimuli and gratings. Regions of interest were subdivided into three-dimensional
      patches (up to 5-15 MUm in diameter) based on response similarity. We hypothesise
      that these patches correspond to individual cells, or segments of blood vessels
      within the inner retina. We observed a close correlation between the patch
      optical responses and mean electrical activity of the visual neurons in afferent
      pathway. While our data suggest that optical imaging of retinal activity is
      possible with high resolution OCT, the technical challenges are not trivial.

PMID- 29379037
TI  - Detection of time-, frequency- and direction-resolved communication within brain
      networks.
AB  - Electroencephalography (EEG) records fast-changing neuronal signalling and
      communication and thus can offer a deep understanding of cognitive processes.
      However, traditional data analyses which employ the Fast-Fourier Transform (FFT)
      have been of limited use as they do not allow time- and frequency-resolved
      tracking of brain activity and detection of directional connectivity. Here, we
      applied advanced qEEG tools using autoregressive (AR) modelling, alongside
      traditional approaches, to murine data sets from common research scenarios: (a)
      the effect of age on resting EEG; (b) drug actions on non-rapid eye movement
      (NREM) sleep EEG (pharmaco-EEG); and (c) dynamic EEG profiles during correct vs
      incorrect spontaneous alternation responses in the Y-maze. AR analyses of short
      data strips reliably detected age- and drug-induced spectral EEG changes, while
      renormalized partial directed coherence (rPDC) reported direction- and time
      resolved connectivity dynamics in mice. Our approach allows for the first time
      inference of behaviour- and stage-dependent data in a time- and frequency
      resolved manner, and offers insights into brain networks that underlie working
      memory processing beyond what can be achieved with traditional methods.

PMID- 29379038
TI  - Cardiac shock wave therapy promotes arteriogenesis of coronary micrangium, and
      ILK is involved in the biomechanical effects by proteomic analysis.
AB  - Cardiac Shock Wave Therapy (CSWT) improves myocardial perfusion and ameliorates
      cardiac remodeling after acute myocardial infarction (AMI), but the precise
      mechanisms remain obscure. Herein, we have applied CSWT to a rat model of AMI to
      demonstrate the arteriogenesis of coronary micrangium and protein expression
      changes in ischemic myocardium after CSWT. Four weeks after CSWT, the fraction
      shortening of rats was improved greatly and the cardiomyocyte apoptosis index was
      significantly lower than the AMI group (P < 0.05). Besides, the fibrotic area was
      markedly decreased in the CSWT group. In the infarction border zone, the
      thickness of smooth muscle layer was expanded apparently after CSWT. Label-free
      quantitative proteomic analysis and bioinformatics analysis revealed that the
      differentially expressed proteins were largely enriched in the focal adhesion
      signaling pathway. And integrin linked kinase (ILK) may be a key factor
      contributed to arteriogenesis of coronary micrangium during CSWT. In conclusion,
      non-invasive cardiac shock wave could promote arteriogenesis of coronary
      micrangium and alleviate myocardial apoptosis and fibrosis after AMI.
      Furthermore, focal adhesion signaling pathway may have a central role in the
      related signal network and ILK was closely related to the arteriogenesis of
      coronary micrangium during CSWT.

PMID- 29379039
TI  - Structure and hydrogen bonding at the limits of liquid water stability.
AB  - Liquid water exhibits unconventional behaviour across its wide range of stability
      - from its unusually high liquid-vapour critical point down to its melting point
      and below where it reaches a density maximum and exhibits negative thermal
      expansion allowing ice to float. Understanding the molecular underpinnings of
      these anomalies presents a challenge motivating the study of water for well over
      a century. Here we examine the molecular structure of liquid water across its
      range of stability, from mild supercooling to the negative pressure and high
      temperature regimes. We use a recently-developed, electronically-responsive model
      of water, constructed from gas-phase molecular properties and incorporating many
      body, long-range interactions to all orders; as a result the model has been shown
      to have high transferability from ice to the supercritical regime. We report a
      link between the anomalous thermal expansion of water and the behaviour of its
      second coordination shell and an anomaly in hydrogen bonding, which persists
      throughout liquid water's range of stability - from the high temperature limit of
      liquid water to its supercooled regime.

PMID- 29379040
TI  - MRI of the cervical spinal cord predicts respiratory dysfunction in ALS.
AB  - For patients with amyotrophic lateral sclerosis (ALS), the primary therapeutic
      goal is to minimize morbidity. Non-invasive ventilation improves survival. We aim
      to assess whether Magnetic Resonance Imaging (MRI) of the cervical spinal cord
      predicts the progression of respiratory disorders in ALS. Brain and spinal MRI
      was repeatedly performed in the SOD1G86R mouse model, in 40 patients and in
      healthy controls. Atrophy, iron overload, white matter diffusivity and neuronal
      loss were assessed. In Superoxide Dismutase-1 (SOD1) mice, iron accumulation
      appeared in the cervical spinal cord at symptom onset but disappeared with
      disease progression (after the onset of atrophy). In ALS patients, the volumes of
      the motor cortex and the medulla oblongata were already abnormally low at the
      time of diagnosis. Baseline diffusivity in the internal capsule was predictive of
      functional handicap. The decrease in cervical spinal cord volume from diagnosis
      to 3 months was predictive of the change in slow vital capacity at 12 months. MRI
      revealed marked abnormalities at the time of ALS diagnosis. Early atrophy of the
      cervical spinal cord may predict the progression of respiratory disorders, and so
      may be of value in patient care and as a primary endpoint in pilot
      neuroprotection studies.

PMID- 29379041
TI  - A Two-Stage Whole-Genome Gene Expression Association Study of Young-Onset
      Hypertension in Han Chinese Population of Taiwan.
AB  - Hypertension is an important public health problem in the world. Since the
      intermediate position of the gene expression between genotype and phenotype makes
      it suitable to link genotype to phenotype, we carried out a two-stage whole
      genome gene expression association study to find differentially expressed genes
      and pathways for hypertension. In the first stage, 126 cases and 149 controls
      were used to find out the differentially expressed genes. In the second stage, an
      independent set of samples (127 cases and 150 controls) was used to validate the
      results. Additionally, we conducted a gene set enrichment analysis (GSEA) to
      search for differentially affected pathways. A total of nine genes were
      implicated in the first stage (Bonferroni-corrected p-value < 0.05). Among these
      genes, ZRANB1, FAM110A, PREP, ANKRD9 and LAMB2 were also differentially expressed
      in an existing database of hypertensive mouse model (GSE19817). A total of 16
      pathways were identified by the GSEA. ZRANB1 and six pathways identified are
      related to TNF-alpha. Three pathways are related to interleukin, one to metabolic
      syndrome, and one to Hedgehog signaling. Identification of these genes and
      pathways suggest the importance of 1. inflammation, 2. visceral fat metabolism,
      and 3. adipocytes and osteocytes homeostasis in hypertension mechanisms and
      complications.

PMID- 29379042
TI  - Maturation of Pain Empathy from Child to Adult Shifts from Single to Multiple
      Neural Rhythms to Support Interoceptive Representations.
AB  - While empathy to the pain of conspecific is evolutionary-ancient and is observed
      in rodents and in primates, it also integrates higher-order affective
      representations. Yet, it is unclear whether human empathy for pain is inborn or
      matures during development and what neural processes underpin its maturation.
      Using magnetoencephalography, we monitored the brain response of children,
      adolescents, and adults (n = 209) to others' pain, testing the shift from
      childhood to adult functioning. Results indicate that children's vicarious
      empathy for pain operates via rudimentary sensory predictions involving alpha
      oscillations in somatosensory cortex, while adults' response recruits advanced
      mechanisms of updating sensory predictions and activating affective empathy in
      viceromotor cortex via higher-level representations involving beta- and gamma
      band activity. Our findings suggest that full-blown empathy to others' pain
      emerges only in adulthood and involves a shift from sensory self-based to
      interoceptive other-focused mechanisms that support human altruism, maintain self
      other differentiation, modulate feedback to monitor other's state, and activate a
      plan of action to alleviate other's suffering.

PMID- 29379043
TI  - Early immune anergy towards recall antigens and mitogens in patients at onset of
      septic shock.
AB  - The pathology of sepsis is typically characterized by an infection and excessive
      initial inflammation including a cytokine storm, followed by a state of immune
      suppression or paralysis. This classical view of a two peak kinetic immune
      response is currently controversially discussed. This study was a sub-study of
      the randomized clinical Trial SISPCT registered with www.clinicaltrials.gov
      (NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with
      severe sepsis and septic shock were incubated for 48 h at 37  degrees C in vitro
      with bacterial or fungal recall-antigens or specific mitogen antigens within 24
      hours of sepsis onset. Recall-antigen stimulation led to a severe dampening of
      normal cytokine release. This immunologic anergy was similarly observed after
      mitogen stimulation. Moreover, patients under hydrocortisone therapy or with
      lowered arterial oxygen tension had further reductions in cytokine levels upon B-
      and T-cell mitogen stimulation. This investigation reveals an early onset of
      immunoparalysis during sepsis. This immune incompetence in mounting an adequate
      response to further infections includes previously sensitized pathogens, as seen
      with recall-antigens. Also, the immune-suppressive role of hydrocortisone and low
      PaO2 is highlighted. Aside from early broad-spectrum antimicrobial therapy, our
      findings reinforce the need for maximal immunological support and protection
      against further infections at the onset of sepsis.

PMID- 29379044
TI  - Coral-like Co3O4 Decorated N-doped Carbon Particles as active Materials for
      Oxygen Reduction Reaction and Supercapacitor.
AB  - Coral reef has a unique dendritic structure with large specific surface area,
      rich pore structure, so that it can be attached to a large number of
      zooxanthellae for gas exchange. Coral reef ecosystems are also known as
      underwater rainforests. Inspired by this biological structure, we designed and
      fabricated coral-like Co3O4 decorated N-doped carbon particles (Co3O4/N-CP). The
      obtained Co3O4/N-CP-900 catalyst shows efficient ORR electrocatalytic
      performances in an alkaline medium with a positive onset and half-wave potentials
      of 0.97 and 0.90 V (vs. RHE), as well as a high diffusion-limited current density
      (5.50 mA cm-2) comparable to that of a Pt/C catalyst (5.15 mA cm-2). It also
      displays better stability and methanol tolerance than commercial Pt/C. In
      addition, the Co3O4/N-CP-900 electrode has a high specific capacitance of 316.2 F
      g-1 in 6 M KOH, as well as good rate capabilities and excellent cycle
      performance. These results are due to large surface area, narrow pore size
      distribution, high density electrochemical energy conversion and storage activity
      centers. This method presented here offers an effective path for the development
      of high performance multi-functional carbon-based materials for ORR and
      supercapacitor applications.

PMID- 29379045
TI  - A facile synthesis of porous graphene for efficient water and wastewater
      treatment.
AB  - The use of two-dimensional graphene-based materials in water treatment has
      recently gained significant attention due to their unique electronic and thermal
      mobility, high surface area, high mechanical strength, excellent corrosion
      resistance and tunable surface chemistry. However, the relatively expensive, poor
      hydrophobicity, low adsorption capacity and recyclability, and complex post
      treatment of the most pristine graphene frameworks limit their practical
      application. Here, we report a facile scalable method to produce highly porous
      graphene from reduced graphene oxide via thermal treatment without addition of
      any catalyst or use of any template. Comparing to conventional graphene
      counterparts, as-prepared porous graphene nanosheets showed evident improvement
      in hydrophobicity, adsorption capacity, and recyclability, making them ideal
      candidate materials for water treatment. Superhydrophobic and superoleophilic
      porous graphene prepared in this work has been demonstrated as effective
      absorbents for a broad range of ions, oils and organic solvents, exhibiting high
      selectivity, good recyclability, and excellent absorption capacities > 90%. The
      synthesis method of porous graphene reported in this paper is easy to implement,
      low cost and scalable. These attributes could contribute towards efficient and
      cost-effective water purification and pollution reduction.

PMID- 29379046
TI  - Human mate-choice copying is domain-general social learning.
AB  - Women appear to copy other women's preferences for men's faces. This 'mate-choice
      copying' is often taken as evidence of psychological adaptations for processing
      social information related to mate choice, for which facial information is
      assumed to be particularly salient. No experiment, however, has directly
      investigated whether women preferentially copy each other's face preferences more
      than other preferences. Further, because prior experimental studies used
      artificial social information, the effect of real social information on
      attractiveness preferences is unknown. We collected attractiveness ratings of
      pictures of men's faces, men's hands, and abstract art given by heterosexual
      women, before and after they saw genuine social information gathered in real time
      from their peers. Ratings of faces were influenced by social information, but no
      more or less than were images of hands and abstract art. Our results suggest that
      evidence for domain-specific social learning mechanisms in humans is weaker than
      previously suggested.

PMID- 29379048
TI  - An MCEM Framework for Drug Safety Signal Detection and Combination from
      Heterogeneous Real World Evidence.
AB  - Delayed drug safety insights can impact patients, pharmaceutical companies, and
      the whole society. Post-market drug safety surveillance plays a critical role in
      providing drug safety insights, where real world evidence such as spontaneous
      reporting systems (SRS) and a series of disproportional analysis serve as a
      cornerstone of proactive and predictive drug safety surveillance. However, they
      still face several challenges including concomitant drugs confounders, rare
      adverse drug reaction (ADR) detection, data bias, and the under-reporting issue.
      In this paper, we are developing a new framework that detects improved drug
      safety signals from multiple data sources via Monte Carlo Expectation
      Maximization (MCEM) and signal combination. In MCEM procedure, we propose a new
      sampling approach to generate more accurate SRS signals for each ADR through
      iteratively down-weighting their associations with irrelevant drugs in case
      reports. While in signal combination step, we adopt Bayesian hierarchical model
      and propose a new summary statistic such that SRS signals can be combined with
      signals derived from other observational health data allowing for related signals
      to borrow statistical support with adjustment of data reliability. They combined
      effectively alleviate the concomitant confounders, data bias, rare ADR and under
      reporting issues. Experimental results demonstrated the effectiveness and
      usefulness of the proposed framework.

PMID- 29379047
TI  - Inferences on specificity recognition at the Malus*domestica gametophytic self
      incompatibility system.
AB  - In Malus * domestica (Rosaceae) the product of each SFBB gene (the pollen
      component of the gametophytic self-incompatibility (GSI) system) of a S-haplotype
      (the combination of pistil and pollen genes that are linked) interacts with a sub
      set of non-self S-RNases (the pistil component), but not with the self S-RNase.
      To understand how the Malus GSI system works, we identified 24 SFBB genes
      expressed in anthers, and determined their gene sequence in nine M. domestica
      cultivars. Expression of these SFBBs was not detected in the petal, sepal,
      filament, receptacle, style, stigma, ovary or young leaf. For all SFBBs (except
      SFBB15), identical sequences were obtained only in cultivars having the same S
      RNase. Linkage with a particular S-RNase was further established using the
      progeny of three crosses. Such data is needed to understand how other genes not
      involved in GSI are affected by the S-locus region. To classify SFBBs
      specificity, the amino acids under positive selection obtained when performing
      intra-haplotypic analyses were used. Using this information and the previously
      identified S-RNase positively selected amino acid sites, inferences are made on
      the S-RNase amino acid properties (hydrophobicity, aromatic, aliphatic, polarity,
      and size), at these positions, that are critical features for GSI specificity
      determination.

PMID- 29379049
TI  - Foxj1 expressing ependymal cells do not contribute new cells to sites of injury
      or stroke in the mouse forebrain.
AB  - The stem cell source of neural and glial progenitors in the periventricular
      regions of the adult forebrain has remained uncertain and controversial. Using a
      cell specific genetic approach we rule out Foxj1+ ependymal cells as stem cells
      participating in neurogenesis and gliogenesis in response to acute injury or
      stroke in the mouse forebrain. Non stem- and progenitor-like responses of Foxj1+
      ependymal cells to injury and stroke remain to be defined and investigated.

PMID- 29379050
TI  - Reconstruction of cysteine biosynthesis using engineered cysteine-free enzymes.
AB  - Amino acid biosynthesis pathways observed in nature typically require enzymes
      that are made with the amino acids they produce. For example, Escherichia coli
      produces cysteine from serine via two enzymes that contain cysteine: serine
      acetyltransferase (CysE) and O-acetylserine sulfhydrylase (CysK/CysM). To solve
      this chicken-and-egg problem, we substituted alternate amino acids in CysE, CysK
      and CysM for cysteine and methionine, which are the only two sulfur-containing
      proteinogenic amino acids. Using a cysteine-dependent auxotrophic E. coli strain,
      CysE function was rescued by cysteine-free and methionine-deficient enzymes, and
      CysM function was rescued by cysteine-free enzymes. CysK function, however, was
      not rescued in either case. Enzymatic assays showed that the enzymes responsible
      for rescuing the function in CysE and CysM also retained their activities in
      vitro. Additionally, substitution of the two highly conserved methionines in CysM
      decreased but did not eliminate overall activity. Engineering amino acid
      biosynthetic enzymes to lack the so-produced amino acids can provide insights
      into, and perhaps eventually fully recapitulate via a synthetic approach, the
      biogenesis of biotic amino acids.

PMID- 29379051
TI  - Global ubiquitination analysis reveals extensive modification and proteasomal
      degradation of cowpox virus proteins, but preservation of viral cores.
AB  - The emergence of Variola virus-like viruses by natural evolution of zoonotic
      Orthopoxviruses, like Cowpox virus (CPXV), is a global health threat. The
      proteasome is essential for poxvirus replication, making the viral components
      interacting with the ubiquitin-proteasome system attractive antiviral targets. We
      show that proteasome inhibition impairs CPXV replication by prevention of
      uncoating, suggesting that uncoating is mediated by proteasomal degradation of
      viral core proteins. Although Orthopoxvirus particles contain considerable
      amounts of ubiquitin, distinct modification sites are largely unknown. Therefore,
      for the first time, we analyzed globally ubiquitination sites in CPXV mature
      virion proteins using LC-MS/MS. Identification of 137 conserved sites in 54 viral
      proteins among five CPXV strains revealed extensive ubiquitination of structural
      core proteins. Moreover, since virions contained primarily K48-linked
      polyubiquitin, we hypothesized that core proteins are modified accordingly.
      However, quantitative analysis of ubiquitinated CPXV proteins early in infection
      showed no proteasomal degradation of core proteins. Instead, our data indicate
      that the recently suggested proteasomal regulation of the uncoating factor E5 is
      a prerequisite for uncoating. Expanding our understanding of poxvirus uncoating
      and elucidating a multitude of novel ubiquitination sites in poxvirus proteins,
      the present study verifies the major biological significance of ubiquitin in
      poxvirus infection.

PMID- 29379052
TI  - Dopamine genes are linked to Extraversion and Neuroticism personality traits, but
      only in demanding climates.
AB  - Cross-national differences in personality have long been recognized in the
      behavioural sciences. However, the origins of such differences are debated.
      Building on reinforcement sensitivity theories and gene-by-environment
      interactions, we predict that personality trait phenotypes linked to dopaminergic
      brain functions (centrally involved in reward processing) diverge most strongly
      in climatically stressful environments, due to shifts in perceived rewards vs
      risks. Individuals from populations with a highly efficient dopamine system are
      biased towards behavioural approach traits (Extraversion and Emotional Stability)
      due to higher perceived reward values, whereas individuals from populations with
      a less efficient dopaminergic system are biased towards risk avoidance. In
      temperate climates, we predict smaller phenotypic differences due to overall
      weakened reward and risk ratios. We calculated a population-level index of
      dopamine functioning using 9 commonly investigated genetic polymorphisms encoding
      dopamine transporters and receptors, derived from a meta-analysis with data from
      805 independent samples involving 127,685 participants across 73 societies or
      territories. We found strong support for the dopamine gene by climatic stress
      interaction: Population genetic differences in dopamine predicted personality
      traits at the population level in demanding climates, but not in temperate, less
      demanding climates, even when controlling for known correlates of personality
      including wealth and parasite stress.

PMID- 29379053
TI  - A Low-Cost Palmtop High-Speed Capillary Electrophoresis Bioanalyzer with Laser
      Induced Fluorescence Detection.
AB  - In this work, we developed a miniaturized palmtop high-speed capillary
      electrophoresis (CE) system integrating whole modules, including picoliter-scale
      sample injection, short capillary-based fast CE, high-voltage power supply,
      orthogonal laser induced fluorescence (LIF) detection, battery, system control,
      on-line data acquisition, processing, storage, and display modules. A strategy of
      minimalist miniaturization combining minimal system design and low-cost system
      construction was adopted to achieve the instrument miniaturization with extremely
      low cost, which is differing from the current microfabrication strategy used in
      most reported miniaturized CE systems. With such a strategy, the total size of
      the bioanalyzer was minimized to 90 * 75 * 77 mm (length * width * height) and
      the instrument cost was reduced to ca. $500, which demonstrated the smallest and
      lowest-cost CE instrument with LIF detection in so far reported systems. The
      present bioanalyzer also exhibited comparable analytical performances to
      previously-reported high-speed CE systems. A limit of detection of 1.02 nM sodium
      fluorescein was obtained. Fast separations were achieved for multiple types of
      samples as amino acids, amino acid enantiomers, DNA fragments, and proteins with
      high efficiency. We applied this instrument in colorectal cancer diagnosis for
      detecting KRAS mutation status by polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) method.

PMID- 29379054
TI  - Aging extension and modifications of lipid metabolism in the monogonont rotifer
      Brachionus koreanus under chronic caloric restriction.
AB  - To examine the interrelationship of aging extension and modification of lipid
      metabolism under chronic caloric restriction (CCR; reduced concentration of the
      green algae Tetraselmis suecica) in the monogonont rotifer Brachionus koreanus,
      we assessed life cycle parameters, fatty acid composition, and expression of
      sirtuin and genes related to lipid metabolism. B. koreanus in the 5% T. suecica
      group showed an increased life span but decreased reproduction. Based on this
      finding, we chose 5% T. suecica for further experiments and compared the data
      with those for 100% T. suecica. Upregulation of sirtuin gene expression was
      observed under CCR. In addition, despite the reduction in the amount of total
      fatty acid (FA) and the area of triacylglycerol, increases in the ratios of
      saturated fatty acid and monounsaturated fatty acid (MUFA) to total FA in 5%
      exposed B. koreanus were observed. Furthermore, mRNA expression analysis
      confirmed that CCR promoted the synthesis of MUFA through Delta9 desaturase.
      Moreover, expression of the docosahexaenoic acid (DHA) synthesizing gene Delta4
      desaturase was also upregulated, together with DHA content. These data suggest
      that CCR modified protein acetylation and lipid metabolism, leading to a decrease
      in reproduction and consequently resulting in life span extension.

PMID- 29379055
TI  - Generalized statistical mechanics of cosmic rays: Application to positron
      electron spectral indices.
AB  - Cosmic ray energy spectra exhibit power law distributions over many orders of
      magnitude that are very well described by the predictions of q-generalized
      statistical mechanics, based on a q-generalized Hagedorn theory for transverse
      momentum spectra and hard QCD scattering processes. QCD at largest center of mass
      energies predicts the entropic index to be [Formula: see text]. Here we show that
      the escort duality of the nonextensive thermodynamic formalism predicts an energy
      split of effective temperature given by Delta [Formula: see text] MeV, where T H
      is the Hagedorn temperature. We carefully analyse the measured data of the AMS-02
      collaboration and provide evidence that the predicted temperature split is indeed
      observed, leading to a different energy dependence of the e+ and e- spectral
      indices. We also observe a distinguished energy scale E* ~ 50 GeV where the e+
      and e- spectral indices differ the most. Linear combinations of the escort and
      non-escort q-generalized canonical distributions yield excellent agreement with
      the measured AMS-02 data in the entire energy range.

PMID- 29379056
TI  - Role of Particle Entanglement in the Violation of Bell Inequalities.
AB  - Entanglement between two separate systems is a necessary resource to violate a
      Bell inequality in a test of local realism. We demonstrate that to overcome the
      Bell bound, this correlation must be accompanied by the entanglement between the
      constituent particles. This happens whenever a super-selection rule prohibits
      coherences between states with different total number of particles and thus
      imposes a constraint on feasible local operations in each sub-system. We show
      that the necessary entanglement between the particles might solely result from
      their indistinguishability. We also give an example of both mode and particle
      entangled pure state, which does not violate any Bell inequality. Our result
      reveals a fundamental relation between the non-locality and the particle
      entanglement.

PMID- 29379057
TI  - STM patterned nanowire measurements using photolithographically defined implants
      in Si(100).
AB  - Using photolithographically defined implant wires for electrical connections, we
      demonstrate measurement of a scanning tunneling microscope (STM) patterned
      nanoscale electronic device on Si(100). By eliminating onerous alignment and
      complex lithography techniques, this approach is accessible to researchers in
      smaller efforts who may not have access to tools like electron beam lithography.
      Electrical contact to the nanodevices is achieved by implanting patterned,
      degenerately doped wires in the substrate using photolithography and commercial
      low energy ion implantation. We bring several isolated, implanted wires to within
      the STM scanner's field of view where the STM can detect and smoothly draw
      contiguous patterns that directly overlap with implant lines for electrical
      connections. This overlapping provides a two-dimensional (2D) overlap interface
      with the 2D electron system, in contrast to many state-of-the-art methods that
      rely on contacting an exposed edge. After the STM pattern is phosphine dosed and
      overgrown with silicon, photolithography is then used again to align (~ 160 MUm)2
      aluminum contact pads onto (~ 200 MUm)2 implanted areas at the ends of the wires.
      We present detailed results that optimize the spacing of neighboring wires while
      maintaining electrical isolation after heating to > 1200  degrees C, a step
      required for in situ Si surface preparation.

PMID- 29379058
TI  - The functional and structural alterations of the striatum in chronic spontaneous
      urticaria.
AB  - The brain has long been known to be the regulation center of itch, but the
      neuropathology of chronic itch, such as chronic spontaneous urticaria (CSU),
      remains unclear. Thus, we aimed to explore the brain areas involved in the
      pathophysiology of CSU in hopes that our results may provide valuable insights
      into the treatment of chronic itch conditions. 40 CSU patients and 40 healthy
      controls (HCs) were recruited. Urticaria activity scores 7 (UAS7) were collected
      to evaluate patient's clinical symptoms. Amplitude of low frequency fluctuations
      (ALFF), voxel-based morphometry (VBM), and seed-based resting-state functional
      connectivity (rs-FC) analysis were used to assess brain activity and related
      plasticity. Compared with HCs, CSU patients exhibited 1) higher ALFF values in
      the right ventral striatum / putamen, which were positively associated with
      clinical symptoms as measured by UAS7; 2) gray matter volume (GMV) increase in
      the right ventral striatum and putamen; and 3) decreased rs-FC between the right
      ventral striatum and the right occipital cortex and between the right putamen and
      the left precentral gyrus. Using multiple-modality brain imaging tools, we
      demonstrated the dysfunction of the striatum in CSU. Our results may provide
      valuable insights into the neuropathology and development of chronic itch.

PMID- 29379059
TI  - Deletion of MCP-1 Impedes Pathogenesis of Acid Ceramidase Deficiency.
AB  - Farber Disease (FD) is an ultra-rare Lysosomal Storage Disorder caused by
      deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency
      manifest a spectrum of symptoms including formation of nodules, painful joints,
      and a hoarse voice. Classic FD patients will develop histiocytes in organs and
      die in childhood. Monocyte chemotactic protein (MCP-1; CCL2) is significantly
      elevated in both FD patients and a mouse model we previously generated. Here, to
      further study MCP-1 in FD, we created an ACDase;MCP-1 double mutant mouse. We
      show that deletion of MCP-1 reduced leukocytosis, delayed weight loss, and
      improved lifespan. Reduced inflammation and fibrosis were observed in livers from
      double mutant animals. Bronchial alveolar lavage fluid analyses revealed a
      reduction in cellular infiltrates and protein accumulation. Furthermore, reduced
      sphingolipid accumulation was observed in the lung and liver but not in the
      brain. The neurological and hematopoietic defects observed in FD mice were
      maintained. A compensatory cytokine response was found in the double mutants,
      however, that may contribute to continued signs of inflammation and injury. Taken
      together, targeting a reduction of MCP-1 opens the door to a better understanding
      of the mechanistic consequences of ceramide accumulation and may even delay the
      progression of FD in some organ systems.

PMID- 29379060
TI  - Automatic Knee Osteoarthritis Diagnosis from Plain Radiographs: A Deep Learning
      Based Approach.
AB  - Knee osteoarthritis (OA) is the most common musculoskeletal disorder. OA
      diagnosis is currently conducted by assessing symptoms and evaluating plain
      radiographs, but this process suffers from subjectivity. In this study, we
      present a new transparent computer-aided diagnosis method based on the Deep
      Siamese Convolutional Neural Network to automatically score knee OA severity
      according to the Kellgren-Lawrence grading scale. We trained our method using the
      data solely from the Multicenter Osteoarthritis Study and validated it on
      randomly selected 3,000 subjects (5,960 knees) from Osteoarthritis Initiative
      dataset. Our method yielded a quadratic Kappa coefficient of 0.83 and average
      multiclass accuracy of 66.71% compared to the annotations given by a committee of
      clinical experts. Here, we also report a radiological OA diagnosis area under the
      ROC curve of 0.93. Besides this, we present attention maps highlighting the
      radiological features affecting the network decision. Such information makes the
      decision process transparent for the practitioner, which builds better trust
      toward automatic methods. We believe that our model is useful for clinical
      decision making and for OA research; therefore, we openly release our training
      codes and the data set created in this study.

PMID- 29379061
TI  - Using DNA origami nanorulers as traceable distance measurement standards and
      nanoscopic benchmark structures.
AB  - In recent years, DNA origami nanorulers for superresolution (SR) fluorescence
      microscopy have been developed from fundamental proof-of-principle experiments to
      commercially available test structures. The self-assembled nanostructures allow
      placing a defined number of fluorescent dye molecules in defined geometries in
      the nanometer range. Besides the unprecedented control over matter on the
      nanoscale, robust DNA origami nanorulers are reproducibly obtained in high
      yields. The distances between their fluorescent marks can be easily analysed
      yielding intermark distance histograms from many identical structures. Thus, DNA
      origami nanorulers have become excellent reference and training structures for
      superresolution microscopy. In this work, we go one step further and develop a
      calibration process for the measured distances between the fluorescent marks on
      DNA origami nanorulers. The superresolution technique DNA-PAINT is used to
      achieve nanometrological traceability of nanoruler distances following the guide
      to the expression of uncertainty in measurement (GUM). We further show two
      examples how these nanorulers are used to evaluate the performance of TIRF
      microscopes that are capable of single-molecule localization microscopy (SMLM).

PMID- 29379063
TI  - Polycomb group protein Suz12 is regulated by a novel miRNA-like small RNA.
AB  - Human mesenchymal stem/stromal cells (hMSCs) provide support for cancer
      progression, partly through their secretome that includes extracellular vesicles
      (EVs). Based on deep-sequencing of small RNA from EVs of MSCs, we now report the
      characterization of novel small RNA, named n-miR-G665, which exhibits typical
      properties of miRNAs. n-miR-G665 sequence is conserved and expressed in most cell
      types. Knockdown studies using anti-agomirs and shRNA studies demonstrated that n
      miR-G665 plays an important role in cell proliferation. Functional assays to
      reveal the targets of n-miR-G665 showed that polycomb protein Suz12 is regulated
      by n-miR-G665, which in turn regulates the expression of n-miR-G665 through
      feedback loop mechanism. These data shed light on a previously unknown novel
      feedback regulatory mechanism for controlling Suz12 expression regulated by
      previously not described miRNA, which may highlight a new therapeutic approach to
      control the polycomb repressor complex 2 activity in cancers.

PMID- 29379062
TI  - Spatiotemporal patterning of EpCAM is important for murine embryonic endo- and
      mesodermal differentiation.
AB  - Epithelial cell adhesion molecule EpCAM is expressed in pluripotent embryonic
      stem cells (ESC) in vitro, but is repressed in differentiated cells, except
      epithelia and carcinomas. Molecular functions of EpCAM, possibly imposing such
      repression, were primarily studied in malignant cells and might not apply to non
      pathologic differentiation. Here, we comprehensively describe timing and
      rationale for EpCAM regulation in early murine gastrulation and ESC
      differentiation using single cell RNA-sequencing datasets, in vivo and in vitro
      models including CRISPR-Cas9-engineered ESC-mutants. We demonstrate expression of
      EpCAM in inner cell mass, epiblast, primitive/visceral endoderm, and strict
      repression in the most primitive, nascent Flk1+ mesoderm progenitors at E7.0.
      Selective expression of EpCAM was confirmed at mid-gestation and perinatal
      stages. The rationale for strict patterning was studied in ESC differentiation.
      Gain/loss-of-function demonstrated supportive functions of EpCAM in achieving
      full pluripotency and guided endodermal differentiation, but repressive functions
      in mesodermal differentiation as exemplified with cardiomyocyte formation. We
      further identified embryonic Ras (ERas) as novel EpCAM interactor of EpCAM and an
      EpCAM/ERas/AKT axis that is instrumental in differentiation regulation. Hence,
      spatiotemporal patterning of EpCAM at the onset of gastrulation, resulting in
      early segregation of interdependent EpCAM+ endodermal and EpCAM-/vimentin+
      mesodermal clusters represents a novel regulatory feature during ESC
      differentiation.

PMID- 29379064
TI  - Dimerization: a structural feature for the protection of hepatitis E virus capsid
      protein against trypsinization.
AB  - Orally-transmitted viruses have evolved in a way to resist the extreme conditions
      of the host's gastrointestinal environment, especially the proteolysis of their
      structural proteins. However, the mechanisms allowing these viruses to survive
      these harsh conditions remain unclear. Hepatitis E virus (HEV) is an orally
      transmitted human pathogen. Its capsid protein contains three domains S, P1 and
      P2. The latter forms a homodimer protruding from the virus shell, making it the
      most exposed part. By combining biochemical and computational methods, we found
      the trypsin digestion sites to be highly conserved among the HEV strains.
      Furthermore, the constructs of the HEV capsid protein that contain an extended P2
      domain were digested within the extensions leaving the P2 domain intact. The
      trypsinization seems to occur in three possible double cleavages at R451-R619,
      R460-R619 or R460-R631.The dimerization disrupts the trypsin action at three main
      sites in the P2 domain R542, K544 and K554. These sites are very exposed in the
      monomeric P2 domain constructs which makes the monomeric forms very susceptible
      to trypsin action. Therefore, we believe that dimerization is a structural
      feature that has been selected by the evolutionary forces to render the HEV
      capsid protein resistant to the host's proteases; an evolutionary feature that
      could be common to some other (if not all) orally-transmitted viruses.

PMID- 29379065
TI  - Preferential amplification of a human mitochondrial DNA deletion in vitro and in
      vivo.
AB  - We generated induced pluripotent stem cells (iPSCs) from patient fibroblasts to
      yield cell lines containing varying degrees of heteroplasmy for a m.13514 A > G
      mtDNA point mutation (2 lines) and for a ~6 kb single, large scale mtDNA deletion
      (3 lines). Long term culture of the iPSCs containing a single, large-scale mtDNA
      deletion showed consistent increase in mtDNA deletion levels with time. Higher
      levels of mtDNA heteroplasmy correlated with increased respiratory deficiency. To
      determine what changes occurred in deletion level during differentiation,
      teratomas comprising all three embryonic germ layers were generated from low
      (20%) and intermediate heteroplasmy (55%) mtDNA deletion clones. Regardless of
      whether iPSCs harbouring low or intermediate mtDNA heteroplasmy were used, the
      final levels of heteroplasmy in all teratoma germ layers increased to a similar
      high level (>60%). Thus, during human stem cell division, cells not only tolerate
      high mtDNA deletion loads but seem to preferentially replicate deleted mtDNA
      genomes. This has implications for the involvement of mtDNA deletions in both
      disease and ageing.

PMID- 29379066
TI  - Design, Bioactivity and structure-activity of 3-Arylpropionate Derivatives as
      Potential High-Efficient Acaricides against Psoroptes Cuniculi.
AB  - A series of 3-aryl propionic esters and their analogues were designed and
      evaluated for acaricidal activity in vitro against Psoroptes cuniculi, a mange
      mite. The structure-activity relationship (SAR) was also discussed. The results
      showed that 6 compounds possessed the excellent activity (LC50 = 0.17-0.24 mM,
      LT50 = 1.5-2.9 h), superior to ivermectin (LC50 = 0.28 mM, LT50 = 8.9 h) (P <
      0.05), a standard drug. Furthermore, 7 compounds showed the good activity (LC50 =
      0.25-0.37 mM, LT50 < 3.9 h), slightly lower or close to that of ivermectin. One
      compound displayed super-fast acaricidal property, far superior to ivermectin.
      SAR analysis found that the ester group is vital for the activity and the small
      steric hindrance adjacent to the ester group is advantageous for the high
      activity. The <C4 linear alcohol esters can give the higher activity. The
      substituents on the 3-phenyl ring or replacement of the 3-phenyl with
      heterocyclic aryl generally decreases the activity. The position of the ester
      group in the ester chain also influences the activity, where the 3-phenyl
      propionate and the benzoate had the highest and lowest activity, respectively.
      Thus, 3-arylpropionates emerged as new and promising high-efficient acaricide
      candidates.

PMID- 29379067
TI  - An improved metrics for osteoclast multinucleation.
AB  - Cell-cell fusion is a key stage in development and maintenance of multinucleated
      cells that resorb bones and form our skeletal muscles and placenta. Here, we
      focus on osteoclast formation to suggest new ways of unbiased presentation of
      cell fusion at given conditions that combine empirical cumulative distribution
      function for the sizes of multinucleated cells with the total number of cell-cell
      fusion events, which generate these cells.

PMID- 29379068
TI  - Investigating the origins of eastern Polynesians using genome-wide data from the
      Leeward Society Isles.
AB  - The debate concerning the origin of the Polynesian speaking peoples has been
      recently reinvigorated by genetic evidence for secondary migrations to western
      Polynesia from the New Guinea region during the 2nd millennium BP. Using genome
      wide autosomal data from the Leeward Society Islands, the ancient cultural hub of
      eastern Polynesia, we find that the inhabitants' genomes also demonstrate
      evidence of this episode of admixture, dating to 1,700-1,200 BP. This supports a
      late settlement chronology for eastern Polynesia, commencing ~1,000 BP, after the
      internal differentiation of Polynesian society. More than 70% of the autosomal
      ancestry of Leeward Society Islanders derives from Island Southeast Asia with the
      lowland populations of the Philippines as the single largest potential source.
      These long-distance migrants into Polynesia experienced additional admixture with
      northern Melanesians prior to the secondary migrations of the 2nd millennium BP.
      Moreover, the genetic diversity of mtDNA and Y chromosome lineages in the Leeward
      Society Islands is consistent with linguistic evidence for settlement of eastern
      Polynesia proceeding from the central northern Polynesian outliers in the Solomon
      Islands. These results stress the complex demographic history of the Leeward
      Society Islands and challenge phylogenetic models of cultural evolution
      predicated on eastern Polynesia being settled from Samoa.

PMID- 29379069
TI  - Phase Coexistence and Kinetic Arrest in the Magnetostructural Transition of the
      Ordered Alloy FeRh.
AB  - In materials where two or more ordering degrees of freedom are closely matched in
      their free energies, coupling between them, or multiferroic behavior can occur.
      These phenomena can produce a very rich phase behavior, as well as emergent
      phases that offer useful properties and opportunities to reveal novel phenomena
      in phase transitions. The ordered alloy FeRh undergoes an antiferromagnetic to
      ferromagnetic phase transition at ~375 K, which illustrates the interplay between
      structural and magnetic order mediated by a delicate energy balance between two
      configurations. We have examined this transition using a combination of high
      resolution x-ray structural and magnetic imaging and comprehensive x-ray magnetic
      circular dichroism spectroscopy. We find that the transition proceeds via a
      defect-driven domain nucleation and growth mechanism, with significant return
      point memory in both the structural and magnetic domain configurations. The
      domains show evidence of inhibited growth after nucleation, resulting in a quasi
      2nd order temperature behavior.

PMID- 29379070
TI  - The transcriptional response to oxidative stress is part of, but not sufficient
      for, insulin resistance in adipocytes.
AB  - Insulin resistance is a major risk factor for metabolic diseases such as Type 2
      diabetes. Although the underlying mechanisms of insulin resistance remain
      elusive, oxidative stress is a unifying driver by which numerous extrinsic
      signals and cellular stresses trigger insulin resistance. Consequently, we sought
      to understand the cellular response to oxidative stress and its role in insulin
      resistance. Using cultured 3T3-L1 adipocytes, we established a model of
      physiologically-derived oxidative stress by inhibiting the cycling of glutathione
      and thioredoxin, which induced insulin resistance as measured by impaired insulin
      stimulated 2-deoxyglucose uptake. Using time-resolved transcriptomics, we found >
      2000 genes differentially-expressed over 24 hours, with specific metabolic and
      signalling pathways enriched at different times. We explored this coordination
      using a knowledge-based hierarchical-clustering approach to generate a temporal
      transcriptional cascade and identify key transcription factors responding to
      oxidative stress. This response shared many similarities with changes observed in
      distinct insulin resistance models. However, an anti-oxidant reversed insulin
      resistance phenotypically but not transcriptionally, implying that the
      transcriptional response to oxidative stress is insufficient for insulin
      resistance. This suggests that the primary site by which oxidative stress impairs
      insulin action occurs post-transcriptionally, warranting a multi-level 'trans
      omic' approach when studying time-resolved responses to cellular perturbations.

PMID- 29379071
TI  - L. plantarum WCFS1 enhances Treg frequencies by activating DCs even in absence of
      sampling of bacteria in the Peyer Patches.
AB  - Probiotics such as L. plantarum WCFS1 can modulate immune responses in healthy
      subjects but how this occurs is still largely unknown. Immune-sampling in the
      Peyer Patches has been suggested to be one of the mechanisms. Here we studied the
      systemic and intestinal immune effects in combination with a trafficking study
      through the intestine of a well-established immunomodulating probiotic, i.e. L.
      plantarum WCFS1. We demonstrate that not more than 2-3 bacteria were sampled and
      in many animals not any bacterium could be found in the PP. Despite this, L.
      plantarum was associated with a strong increase in infiltration of regulatory
      CD103+ DCs and generation of regulatory T cells in the spleen. Also, a reduced
      splenic T helper cell cytokine response was observed after ex vivo restimulation.
      L. plantarum enhanced Treg cells and attenuated the T helper 2 response in
      healthy mice. We demonstrate that, in healthy mice, immune sampling is a rare
      phenomenon and not required for immunomodulation. Also in absence of any sampling
      immune activation was found illustrating that host-microbe interaction on the
      Peyer Patches was enough to induce immunomodulation of DCs and T-cells.

PMID- 29379072
TI  - Manipulation of Pro-Sociality and Rule-Following with Non-invasive Brain
      Stimulation.
AB  - Decisions are often governed by rules on adequate social behaviour. Recent
      research suggests that the right lateral prefrontal cortex (rLPFC) is involved in
      the implementation of internal fairness rules (norms), by controlling the impulse
      to act selfishly. A drawback of these studies is that the assumed norms and
      impulses have to be deduced from behaviour and that norm-following and pro
      sociality are indistinguishable. Here, we directly confronted participants with a
      rule that demanded to make advantageous or disadvantageous monetary allocations
      for themselves or another person. To disentangle its functional role in rule
      following and pro-sociality, we divergently manipulated the rLPFC by applying
      cathodal or anodal transcranial direct current stimulation (tDCS). Cathodal tDCS
      increased participants' rule-following, even of rules that demanded to lose money
      or hurt another person financially. In contrast, anodal tDCS led participants to
      specifically violate more often those rules that were at odds with what
      participants chose freely. Brain stimulation over the rLPFC thus did not simply
      increase or decrease selfishness. Instead, by disentangling rule-following and
      pro-sociality, our results point to a broader role of the rLPFC in integrating
      the costs and benefits of rules in order to align decisions with internal goals,
      ultimately enabling to flexibly adapt social behaviour.

PMID- 29379073
TI  - Growth kinetics of Cu6Sn5 intermetallic compound in Cu-liquid Sn interfacial
      reaction enhanced by electric current.
AB  - In this paper, electric currents with the densities of 1.0 * 102 A/cm2 and 2.0 *
      102 A/cm2 were imposed to the Cu-liquid Sn interfacial reaction at 260  degrees C
      and 300  degrees C with the bonding times from 15 min to 960 min. Unlike the
      symmetrical growth following a cubic root dependence on time during reflowing,
      the Cu6Sn5 growth enhanced by solid-liquid electromigration followed a linear
      relationship with time. The elevated electric current density and reaction
      temperature could greatly accelerate the growth of Cu6Sn5, and could induce the
      formation of cellular structures on the surfaces because of the constitutional
      supercooling effect. A growth kinetics model of Cu6Sn5 based on Cu concentration
      gradient was presented, in which the dissolution of cathode was proved to be the
      controlling step. This model indicates that higher current density, higher
      temperature and larger joint width were in favor of the dissolution of Cu.
      Finally, the shear strengths of joints consisted of different intermetallic
      compound microstructures were evaluated. The results showed that the Cu6Sn5-based
      joint could achieve comparable shear strength with Sn-based joint.

PMID- 29379074
TI  - Multiplane and Spectrally-Resolved Single Molecule Localization Microscopy with
      Industrial Grade CMOS cameras.
AB  - This work explores the use of industrial grade CMOS cameras for single molecule
      localization microscopy (SMLM). We show that industrial grade CMOS cameras
      approach the performance of scientific grade CMOS cameras at a fraction of the
      cost. This makes it more economically feasible to construct high-performance
      imaging systems with multiple cameras that are capable of a diversity of
      applications. In particular we demonstrate the use of industrial CMOS cameras for
      biplane, multiplane and spectrally resolved SMLM. We also provide open-source
      software for simultaneous control of multiple CMOS cameras and for the reduction
      of the movies that are acquired to super-resolution images.

PMID- 29379075
TI  - Atypical changes in DRG neuron excitability and complex pain phenotype associated
      with a Nav1.7 mutation that massively hyperpolarizes activation.
AB  - Sodium channel Nav1.7 plays a central role in pain-signaling: gain-of-function
      Nav1.7 mutations usually cause severe pain and loss-of-function mutations produce
      insensitivity to pain. The Nav1.7 I234T gain-of-function mutation, however, is
      linked to a dual clinical presentation of episodic pain, together with absence of
      pain following fractures, and corneal anesthesia. How a Nav1.7 mutation that
      produces gain-of-function at the channel level causes clinical loss-of-function
      has remained enigmatic. We show by current-clamp that expression of I234T in
      dorsal root ganglion (DRG) neurons produces a range of membrane depolarizations
      including a massive shift to >-40 mV that reduces excitability in a small number
      of neurons. Dynamic-clamp permitted us to mimic the heterozygous condition via
      replacement of 50% endogenous wild-type Nav1.7 channels by I234T, and confirmed
      that the I234T conductance could drastically depolarize DRG neurons, resulting in
      loss of excitability. We conclude that attenuation of pain sensation by I234T is
      caused by massively depolarized membrane potential of some DRG neurons which is
      partly due to enhanced overlap between activation and fast-inactivation,
      impairing their ability to fire. Our results demonstrate how a Nav1.7 mutation
      that produces channel gain-of-function can contribute to a dual clinical
      presentation that includes loss of pain sensation at the clinical level.

PMID- 29379076
TI  - Core-shell magnetoelectric nanorobot - A remotely controlled probe for targeted
      cell manipulation.
AB  - We have developed a remotely controlled dynamic process of manipulating targeted
      biological live cells using fabricated core-shell nanocomposites, which comprises
      of single crystalline ferromagnetic cores (CoFe2O4) coated with crystalline
      ferroelectric thin film shells (BaTiO3). We demonstrate them as a unique family
      of inorganic magnetoelectric nanorobots (MENRs), controlled remotely by applied
      a.c. or d.c. magnetic fields, to perform cell targeting, permeation, and
      transport. Under a.c. magnetic field excitation (50 Oe, 60 Hz), the MENR acts as
      a localized electric periodic pulse generator and can permeate a series of
      misaligned cells, while aligning them to an equipotential mono-array by inducing
      inter-cellular signaling. Under a.c. magnetic field (40 Oe, 30 Hz) excitation,
      MENRs can be dynamically driven to a targeted cell, avoiding untargeted cells in
      the path, irrespective of cell density. D.C. magnetic field (-50 Oe) excitation
      causes the MENRs to act as thrust generator and exerts motion in a group of
      cells.

PMID- 29379077
TI  - Immunomodulatory capacity of the serotonin receptor 5-HT2B in a subset of human
      dendritic cells.
AB  - Serotonin is a monoamine neurotransmitter that signals through a wide array of
      receptors (5-HT1-7) many of which are also involved in immune processes.
      Dendritic cells (DCs) are crucial players in immune defense by bridging innate
      and adaptive immune responses via their vast repertoire of pattern recognition
      receptors and antigen-presenting capability. Although serotonin is known to
      influence immunity at many levels, cell type-specific expression and function of
      its receptors remains poorly understood. Here we aimed to study 5-HT1-7
      expression and function in CD1a- and CD1a+ human monocyte-derived DCs (moDCs). We
      found that the 5-HT2B receptor-subtype is solely expressed by the inflammatory
      CD1a+ moDC subset. Specific 5-HT2B activation potently inhibited TLR2, TLR3, and
      TLR7/8-induced proinflammatory cytokine and chemokine (TNF-alpha, IL-6, IL-8, IP
      10, IL-12) but not type I interferon-beta responses. 5-HT2B agonism also
      interfered with the polarization of CD1a+ moDC-primed CD4+ T cells towards
      inflammatory Th1 and Th17 effector lymphocytes. Here we report the subset
      specific expression and immunomodulatory function of 5-HT2B in human moDCs. Our
      results expand the biological role of 5-HT2B which may act not only as a
      neurotransmitter receptor, but also as an important modulator of both innate and
      adaptive immune responses.

PMID- 29379079
TI  - A novel PAX7 10-bp indel variant modulates promoter activity, gene expression and
      contributes to different phenotypes of Chinese cattle.
AB  - Paired box 7 (PAX7) gene regulates the conversion of muscle satellite cells into
      myogenic cells and participates in multi-step processes in myogenesis. Expression
      levels of PAX7 are decisive for its regulatory function. Previous reports
      revealed that PAX7 were responsible for the developmental traits of muscle. The
      relationship of the PAX7 promoter variants and livestock phenotypic traits has
      not been fully elucidated. We detected a novel 10-bp insertion/deletion (indel)
      polymorphism in the bovine PAX7 promoter and revealed that the indel altered the
      binding of the transcriptional factor ZNF219. Luciferase reporter assay showed
      that deletion-deletion (Del-Del) genotype of the PAX7 gene showed 2.79-fold
      higher promoter activity than the insertion-insertion (Ins-Ins) genotype (P <
      0.05), and ZNF219 overexpression significantly diminished the luciferase activity
      in Ins-Ins groups. Moreover, the expression of PAX7 and its down-stream genes
      were detected in fetal skeletal muscle of cattle with different PAX7 genotypes,
      where the Del-Del genotype also displayed high expression levels. Statistical
      association analysis demonstrated that this indel had significant effects on
      early growth traits in cattle. These findings provide a complete overview of the
      function of the PAX7 10-bp variant, which may have potential as a genetic marker
      for marker-assisted selection in improving economically significant traits of
      cattle.

PMID- 29379080
TI  - Bridging the connection between effective viscosity and electrical conductivity
      through water content in the upper mantle.
AB  - Upper mantle viscosity plays a key role in understanding plate tectonics and is
      usually extrapolated from laboratory-based creep measurements of upper mantle
      conditions or constrained by modeling geodetic and post-seismic observations. At
      present, an effective method to obtain a high-resolution viscosity structure is
      still lacking. Recently, a promising estimation of effective viscosity was
      obtained from a transform derived from the results of magnetotelluric imaging.
      Here, we build a relationship between effective viscosity and electrical
      conductivity in the upper mantle using water content. The contribution of water
      content to the effective viscosity is isolated in a flow law with reference to
      relatively dry conditions in the upper mantle. The proposed transform is robust
      and has been verified by application to data synthesized from an intraoceanic
      subduction zone model. We then apply the method to transform an electrical
      conductivity cross-section across the Yangtze block and the North China Craton.
      The results show that the effective viscosity structure coincides well with that
      estimated from other independent datasets at depths of 40 to 80 km but differs
      slightly at depths of 100 to 200 km. We briefly discussed the potentials and
      associated problems for application.

PMID- 29379078
TI  - Control of primary metabolism by a virulence regulatory network promotes
      robustness in a plant pathogen.
AB  - Robustness is a key system-level property of living organisms to maintain their
      functions while tolerating perturbations. We investigate here how a regulatory
      network controlling multiple virulence factors impacts phenotypic robustness of a
      bacterial plant pathogen. We reconstruct a cell-scale model of Ralstonia
      solanacearum connecting a genome-scale metabolic network, a virulence
      macromolecule network, and a virulence regulatory network, which includes 63
      regulatory components. We develop in silico methods to quantify phenotypic
      robustness under a broad set of conditions in high-throughput simulation
      analyses. This approach reveals that the virulence regulatory network exerts a
      control of the primary metabolism to promote robustness upon infection. The
      virulence regulatory network plugs into the primary metabolism mainly through the
      control of genes likely acquired via horizontal gene transfer, which results in a
      functional overlay with ancestral genes. These results support the view that
      robustness may be a selected trait that promotes pathogenic fitness upon
      infection.

PMID- 29379081
TI  - Ordered states in the Kitaev-Heisenberg model: From 1D chains to 2D honeycomb.
AB  - We study the ground state of the 1D Kitaev-Heisenberg (KH) model using the
      density-matrix renormalization group and Lanczos exact diagonalization methods.
      We obtain a rich ground-state phase diagram as a function of the ratio between
      Heisenberg (J = cosphi) and Kitaev (K = sinphi) interactions. Depending on the
      ratio, the system exhibits four long-range ordered states: ferromagnetic-z,
      ferromagnetic-xy, staggered-xy, Neel-z, and two liquid states: Tomonaga-Luttinger
      liquid and spiral-xy. The two Kitaev points [Formula: see text] and [Formula: see
      text] are singular. The phi-dependent phase diagram is similar to that for the 2D
      honeycomb-lattice KH model. Remarkably, all the ordered states of the honeycomb
      lattice KH model can be interpreted in terms of the coupled KH chains. We also
      discuss the magnetic structure of the K-intercalated RuCl3, a potential Kitaev
      material, in the framework of the 1D KH model. Furthermore, we demonstrate that
      the low-lying excitations of the 1D KH Hamiltonian can be explained within the
      combination of the known six-vertex model and spin-wave theory.

PMID- 29379082
TI  - Supplement of Betaine into Embryo Culture Medium Can Rescue Injury Effect of
      Ethanol on Mouse Embryo Development.
AB  - Mammal embryos can be impaired by mother's excessive ethanol uptake, which
      induces a higher level of reactive oxygen species (ROS) and interferes in one
      carbon unit metabolism. Here, our analysis by in vitro culture system reveals
      immediate effect of ethanol in medium on mouse embryo development presents
      concentration dependent. A preimplantation embryo culture using medium contained
      1% ethanol could impact greatly early embryos development, and harmful effect of
      ethanol on preimplantation embryos would last during the whole development period
      including of reducing ratio of blastocyst formation and implantation, and
      deteriorating postimplantation development. Supplement of 50 MUg/ml betaine into
      culture medium can effectively reduce the level of ROS caused by ethanol in
      embryo cells and rescue embryo development at each stage damaged by ethanol, but
      supplement of glycine can't rescue embryo development as does betaine. Results of
      5-methylcytosine immunodetection indicate that supplement of betaine into medium
      can reduce the rising global level of genome DNA methylation in blastocyst cells
      caused by 1% ethanol, but glycine can't play the same impact. The current
      findings demonstrate that betaine can effectively rescue development of embryos
      harmed by ethanol, and possibly by restoring global level of genome DNA
      methylation in blastocysts.

PMID- 29379083
TI  - Arms race of temporal partitioning between carnivorous and herbivorous mammals.
AB  - Reciprocal coevolutionary changes in predation and anti-predator behaviours have
      long been hypothesized, but evolutionary-scale evidence is rare. Here, we
      reconstructed the evolutionary-scale changes in the diel activity patterns of a
      predator-prey system (carnivorous and herbivorous mammals) based on a molecular
      phyloecological approach, providing evidence of long-term antagonistic
      coevolutionary changes in their diel activities. Our molecular reconstruction of
      diel activity patterns, which is supported by morphological evidence,
      consistently showed that carnivorous mammals were subjected to a shift from
      diurnality to nocturnality, while herbivorous mammals experienced a shift from
      nocturnality to diurnality during their evolutionary histories. A shift in the
      diel activity of the herbivores as a result of carnivore avoidance is
      hypothesized based on molecular, morphological and behavioural evidence, and our
      results suggest an evolutionary-scale arms race of diel activity shifts between
      carnivorous and herbivorous mammals.

PMID- 29379084
TI  - Alternative use of Bacillus subtilis spores: protection against environmental
      oxidative stress in human normal keratinocytes.
AB  - Inorganic trivalent arsenic is a major environmental pollutant and exposure to
      human results in many pathologies, including keratosis and carcinoma. Here, we
      analyzed the effects of B. subtilis spores on human normal keratinocytes in the
      presence of sodium arsenite oxidative stress. Pre-treatment of cells with spores
      before inducing oxidative stress was able to keep normal levels of intracellular
      ROS, GSH and lipid peroxidation, as well as to inhibit the activation of the MAPK
      cascade. Moreover, spores showed a positive effect on cell proliferation,
      probably due to their binding on the cell surface and the activation of
      intracellular catalases. We found that spores exert their protective effect by
      the nuclear translocation of Nrf-2, involved in the activation of stress response
      genes. This, in turn, resulted in a protective effect against sodium arsenite
      stress injury, as oxidative stress markers were reported to physiological levels
      when cells were stressed before incubating them with spores. Therefore, B.
      subtilis spores can be considered as a new agent to counteract oxidative stress
      on normal human keratinocytes.

PMID- 29379085
TI  - Efficient strategy for introducing large and multiple changes in plasmid DNA.
AB  - While the QuikChange site-directed mutagenesis method and its later modifications
      are extremely useful and simple, they suffer from several drawbacks. Here, we
      propose a new method, named LFEAP mutagenesis (Ligation of Fragment Ends After
      PCR) for creating various mutations in plasmid by leveraging three existing
      concepts: inverse PCR, single primer PCR, and sticky-end assembly. The first
      inverse PCR on the target plasmid yielded linearized DNA fragments with mutagenic
      ends, and a second single primer PCR resulted in complementary single-stranded
      DNA fragments with the addition of overhangs at the 5' end of each strand. The
      resulting single strands were then annealed to produce double-stranded DNA with
      free 5' single-stranded DNA tails. These products with compatible sticky ends
      were efficiently assembled into a circular, mutagenized plasmid. With this
      strategy, multiple simultaneous changes (up to 15) and mutations in large
      plasmids (up to 50 kb) were achieved with high efficiency and fidelity. LFEAP
      mutagenesis is a versatile method that offers significant advantages for
      introducing large and multiple changes in plasmid DNA.

PMID- 29379086
TI  - Early modulation of intra-cortical inhibition during the observation of action
      mistakes.
AB  - Errors while performing an action are fundamental for learning. During
      interaction others' errors must be monitored and taken into account to allow
      joint action coordination and imitation learning. This monitoring relies on an
      action observation network (AON) mainly based on parietofrontal recurrent
      circuits. Although different studies suggest that inappropriate actions may
      rapidly be inhibited during execution, little is known about the modulation of
      the AON when an action misstep is shown. Here we used single and paired pulse
      transcranial magnetic stimulation to assess corticospinal excitability,
      intracortical facilitation and intracortical inhibition at different time
      intervals (120, 180, 240 ms) after the visual presentation of a motor execution
      error. Results show a specific and early (120 ms) decrease of intracortical
      inhibition likely because of a significant mismatch between the observed
      erroneous action and observer's expectations. Indeed, as proposed by the top-down
      predictive framework, the motor system may be involved in the generation of these
      error signals and our data show that this mechanism could rely on the early
      decrease of intracortical inhibition within the corticomotor system.

PMID- 29379087
TI  - Active sites of copper-complex catalytic materials for electrochemical carbon
      dioxide reduction.
AB  - Restructuring-induced catalytic activity is an intriguing phenomenon of
      fundamental importance to rational design of high-performance catalyst materials.
      We study three copper-complex materials for electrocatalytic carbon dioxide
      reduction. Among them, the copper(II) phthalocyanine exhibits by far the highest
      activity for yielding methane with a Faradaic efficiency of 66% and a partial
      current density of 13 mA cm-2 at the potential of - 1.06 V versus the reversible
      hydrogen electrode. Utilizing in-situ and operando X-ray absorption spectroscopy,
      we find that under the working conditions copper(II) phthalocyanine undergoes
      reversible structural and oxidation state changes to form ~ 2 nm metallic copper
      clusters, which catalyzes the carbon dioxide-to-methane conversion. Density
      functional calculations rationalize the restructuring behavior and attribute the
      reversibility to the strong divalent metal ion-ligand coordination in the
      copper(II) phthalocyanine molecular structure and the small size of the generated
      copper clusters under the reaction conditions.

PMID- 29379088
TI  - The inflammatory effects of TNF-alpha and complement component 3 on coagulation.
AB  - Tissue necrosis factor-alpha (TNF-alpha) and complement component 3 (C3) are two
      well-known pro-inflammatory molecules. When TNF-alpha is upregulated, it
      contributes to changes in coagulation and causes C3 induction. They both interact
      with receptors on platelets and erythrocytes (RBCs). Here, we look at the
      individual effects of C3 and TNF-alpha, by adding low levels of the molecules to
      whole blood and platelet poor plasma. We used thromboelastography, wide-field
      microscopy and scanning electron microscopy to study blood clot formation, as
      well as structural changes to RBCs and platelets. Clot formation was
      significantly different from the naive sample for both the molecules.
      Furthermore, TNF-alpha exposure to whole blood resulted in platelet clumping and
      activation and we noted spontaneous plasma protein dense matted deposits. C3
      exposure did not cause platelet aggregation, and only slight pseudopodia
      formation was noted. Therefore, although C3 presence has an important function to
      cause TNF-alpha release, it does not necessarily by itself cause platelet
      activation or RBC damage at these low concentrations. We conclude by suggesting
      that our laboratory results can be translated into clinical practice by
      incorporating C3 and TNF-alpha measurements into broad spectrum analysis assays,
      like multiplex technology, as a step closer to a patient-orientated, precision
      medicine approach.

PMID- 29379090
TI  - GO FEAT: a rapid web-based functional annotation tool for genomic and
      transcriptomic data.
AB  - Downstream analysis of genomic and transcriptomic sequence data is often executed
      by functional annotation that can be performed by various bioinformatics tools
      and biological databases. However, a full fast integrated tool is not available
      for such analysis. Besides, the current available software is not able to produce
      analytic lists of annotations and graphs to help users in evaluating the output
      results. Therefore, we present the Gene Ontology Functional Enrichment Annotation
      Tool (GO FEAT), a free web platform for functional annotation and enrichment of
      genomic and transcriptomic data based on sequence homology search. The analysis
      can be customized and visualized as per users' needs and specifications. GO FEAT
      is freely available at http://computationalbiology.ufpa.br/gofeat/ and its source
      code is hosted at https://github.com/fabriciopa/gofeat .

PMID- 29379089
TI  - The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity:
      implications in HIV-associated neurocognitive disorders.
AB  - Currently, there are no specific therapies to treat HIV-1 associated
      neurocognitive disorders (HAND). The HIV-1 envelope, gp120, induces
      neuropathological changes similar to those in HAND patients; furthermore, it
      triggers an upregulation of the alpha7-nicotinic acetylcholine receptor (alpha7
      nAChR), facilitating intracellular calcium overload and neuronal cell death.
      Using a gp120IIIB-transgenic mouse (gp120-tgm) model, we demonstrate that alpha7
      nAChRs are upregulated on striatal neurons. Activation of alpha7-nAChRs leads to
      an increase in both intracellular calcium and percentage of apoptotic cells,
      which can be abrogated by antagonizing the receptor, suggesting a role for alpha7
      nAChRs in gp120-induced neurotoxicity. Moreover, we demonstrate for the first
      time that gp120-tgm have learning deficiencies on a striatum-dependent behavioral
      task. They also show locomotor deficiencies, which improved with alpha7-nAChR
      antagonists, further supporting a role for this receptor in gp120-induced
      neurotoxicity. Together, these results uncover a new mechanism through which
      gp120-induced modulation of alpha7-nAChRs in the striatum can contribute to HAND
      development.

PMID- 29379091
TI  - Pisa Syndrome in Parkinson's Disease: Pathogenic Roles of Verticality Perception
      Deficits.
AB  - We elucidated whether verticality misperception is associated with the generation
      of Pisa syndrome (PS) in patients with Parkinson's disease (PD). To examine the
      heterogenous influence of verticality perception, we also identified the
      characteristics distinguishing between PD patients with PS who tilted toward the
      deviation of perceived verticality and those who did not. Subjective visual
      vertical (SVV) testing was performed in 54 PD patients with PS and 36 without PS
      to measure verticality perception. Other potential risk factors for PS were
      evaluated by assessing the asymmetry of motor symptoms, EMG activities of
      paraspinal muscles, bithermal caloric tests, back pain history, and Berg Balance
      Scale. Abnormal SVV (odds ratio (OR) 18.40, p = 0.006), postural imbalance (OR
      0.71, p = 0.046), and unilateral EMG hyperactivity of paraspinal muscles (OR
      39.62, p = 0.027) were independent contributors to PS. In subgroup analysis, EMG
      hyperactivity of paraspinal muscles contralateral to the leaning side and
      postural imbalance were associated with PD patients with PS who tilted toward the
      SVV deviation, whereas back pain was more frequent in those who did not.
      Verticality misperception is a potent risk factor for PS in PD and contributes
      differentially to PS depending on the congruence between its direction and PS
      direction, indicating distinct pathogenic roles.

PMID- 29379092
TI  - Malignancy dominated with rheumatic manifestations: A retrospective single-center
      analysis.
AB  - Paraneoplastic rheumatic syndromes comprise a heterogeneous group of disorders
      characterized by typical rheumatic manifestations but without direct invasion by
      the tumor or metastases. The clinical features and malignancy-associated risk
      factors of 21 patients with paraneoplastic rheumatic syndromes, including 11 men
      and 10 women with a mean age of 56.3 +/- 13.1 years, were characterized by a
      retrospective review. All patients were diagnosed with malignancy within 2 years
      of rheumatism diagnosis. Patients suffering from solid malignancies accounted for
      the majority (62%); hematological malignancies were observed in the remainder.
      Arthritis (48%), lymph node enlargement (38%), skin rash (38%), weight loss
      (29%), fever/chills (24%), fatigue (24%), muscle soreness (24%) and smoking
      history (29%) were common findings. Except for 8 patients (38%) who tested
      positive for anti-nuclear antibody (ANA) and 9 positive for rheumatoid factor
      (RF), all patients tested negative for anti-extractable nuclear antigen (ENA)
      antibodies. Rheumatic disorders with a typical clinical presentation in older
      patients and nonspecific systemic features should alert clinicians to search for
      an occult malignancy. Patients with rheumatic disease must be closely followed to
      screen for malignancies, particularly within 2 years of rheumatism diagnosis.

PMID- 29379094
TI  - Current distribution across type II superconducting films: a new vortex-free
      critical state.
AB  - The current distribution across the thickness of a current-carrying rectangular
      film in the Meissner state was established long ago by the London brothers. The
      distribution across the width is more complicated but was later shown to be
      highly non-uniform, diverging at the edges. Accordingly, the standard view for
      type II superconductors is that vortices enter at the edges and, with increasing
      current, are driven inwards until they self-annihilate at the centre, causing
      dissipation. This condition is presumed to define the critical current. However
      we have shown that, under self-field (no external field), the transport critical
      current is a London surface current where the surface current density equals the
      critical field divided by lambda, across the entire width. The critical current
      distribution must therefore be uniform. Here we report studies of the current and
      field distribution across commercial YBa2Cu3 O7 conductors and confirm the
      accepted non-uniform distribution at low current but demonstrate a radical
      crossover to a uniform distribution at critical current. This crossover ends
      discontinuously at a singularity and calculations quantitatively confirm these
      results in detail. The onset of self-field dissipation is, unexpectedly,
      thermodynamic in character and the implied vortex-free critical state seems to
      require new physics.

PMID- 29379093
TI  - MCPIP1-induced autophagy mediates ischemia/reperfusion injury in endothelial
      cells via HMGB1 and CaSR.
AB  - Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a important role
      in ischemia/reperfusion (I/R) injury. Autophagy is involved in activating
      endothelial cells in response to I/R. However, researchers have not clearly
      determined whether MCPIP1 mediates I/R injury in endothelial cells via autophagy,
      and its downstream mechanism remains unclear. Western blotting analyses and
      immunocytochemistry were applied to detect protein levels were detected in
      HUVECs. An in vitro scratch assay was used to detect cell migration. Cells were
      transfected with siRNAs to knockdown MCPIP1 and high mobility group box 1 (HMGB1)
      expression. The pharmacological activator of autophagy rapamycin and the specific
      calcium-sensing receptor (CaSR) inhibitor NPS-2143 were used to confirm the roles
      of autophagy and CaSR in I/R injury. I/R induced HMGB1 and CaSR expression, which
      subsequently upreguated the migration and apoptosis of HUVECs and coincided with
      the increase of autophagy. HMGB1 was involved in cell migration, whereas CaSR
      specifically participated in I/R-induced HUVEC apoptosis. Based on these
      findings, I/R-induced MCPIP1 expression regulates the migration and apoptosis of
      HUVECs via HMGB1 and CaSR, respectively, suggesting a new therapeutic targetof
      I/R injury.

PMID- 29379095
TI  - The motilin agonist erythromycin increases hunger by modulating homeostatic and
      hedonic brain circuits in healthy women: a randomized, placebo-controlled study.
AB  - The motilin agonist, erythromycin, induces gastric phase III of the migrating
      motor complex, which in turn generates hunger peaks. To identify the brain
      mechanisms underlying these orexigenic effects, 14 healthy women participated in
      a randomized, placebo-controlled crossover study. Functional magnetic resonance
      brain images were acquired for 50 minutes interprandially. Intravenous infusion
      of erythromycin (40 mg) or saline started 10 minutes after the start of scanning.
      Blood samples (for glucose and hormone levels) and hunger ratings were collected
      at fixed timepoints. Thirteen volunteers completed the study, without any adverse
      events. Brain regions involved in homeostatic and hedonic control of appetite and
      food intake responded to erythromycin, including pregenual anterior cingulate
      cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum
      and putamen bilaterally, right accumbens, hypothalamus, and midbrain.
      Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased
      after erythromycin. Hunger were higher after erythromycin, and these differences
      covaried with the brain response in most of the abovementioned regions. The
      motilin agonist erythromycin increases hunger by modulating neurocircuitry
      related to homeostatic and hedonic control of appetite and feeding. These results
      confirm recent behavioural findings identifying motilin as a key orexigenic
      hormone in humans, and identify the brain mechanisms underlying its effect.

PMID- 29379097
TI  - Multi-wavelength emission from a single InGaN/GaN nanorod analyzed by
      cathodoluminescence hyperspectral imaging.
AB  - Multiple luminescence peaks emitted by a single InGaN/GaN quantum-well(QW)
      nanorod, extending from the blue to the red, were analysed by a combination of
      electron microscope based imaging techniques. Utilizing the capability of
      cathodoluminescence hyperspectral imaging it was possible to investigate spatial
      variations in the luminescence properties on a nanoscale. The high optical
      quality of a single GaN nanorod was demonstrated, evidenced by a narrow band-edge
      peak and the absence of any luminescence associated with the yellow defect band.
      Additionally two spatially confined broad luminescence bands were observed,
      consisting of multiple peaks ranging from 395 nm to 480 nm and 490 nm to 650 nm.
      The lower energy band originates from broad c-plane QWs located at the apex of
      the nanorod and the higher energy band from the semipolar QWs on the pyramidal
      nanorod tip. Comparing the experimentally observed peak positions with peak
      positions obtained from plane wave modelling and 3D finite difference time
      domain(FDTD) modelling shows modulation of the nanorod luminescence by cavity
      modes. By studying the influence of these modes we demonstrate that this can be
      exploited as an additional parameter in engineering the emission profile of LEDs.

PMID- 29379096
TI  - The antidepressant fluoxetine acts on energy balance and leptin sensitivity via
      BDNF.
AB  - Leptin and Brain Derived Neurotrophic Factor (BDNF) pathways are critical players
      in body weight homeostasis. Noninvasive treatments like environmental stimulation
      are able to increase response to leptin and induce BDNF expression in the brain.
      Emerging evidences point to the antidepressant selective serotonin reuptake
      inhibitor Fluoxetine (FLX) as a drug with effects similar to environmental
      stimulation. FLX is known to impact on body weight, with mechanisms yet to be
      elucidated. We herein asked whether FLX affects energy balance, the leptin system
      and BDNF function. Adult lean male mice chronically treated with FLX showed
      reduced weight gain, higher energy expenditure, increased sensitivity to acute
      leptin, increased hypothalamic BDNF expression, associated to changes in white
      adipose tissue expression typical of "brownization". In the Ntrk2tm1Ddg/J model,
      carrying a mutation in the BDNF receptor Tyrosine kinase B (TrkB), these effects
      are partially or totally reversed. Wild type obese mice treated with FLX showed
      reduced weight gain, increased energy output, and differently from untreated
      obese mice, a preserved acute response to leptin in terms of activation of the
      intracellular leptin transducer STAT3. In conclusion, FLX impacts on energy
      balance and induces leptin sensitivity and an intact TrkB function is required
      for these effects to take place.

PMID- 29379098
TI  - DNA structure at the plasmid origin-of-transfer indicates its potential transfer
      range.
AB  - Horizontal gene transfer via plasmid conjugation enables antimicrobial resistance
      (AMR) to spread among bacteria and is a major health concern. The range of
      potential transfer hosts of a particular conjugative plasmid is characterised by
      its mobility (MOB) group, which is currently determined based on the amino acid
      sequence of the plasmid-encoded relaxase. To facilitate prediction of plasmid MOB
      groups, we have developed a bioinformatic procedure based on analysis of the
      origin-of-transfer (oriT), a merely 230 bp long non-coding plasmid DNA region
      that is the enzymatic substrate for the relaxase. By computationally interpreting
      conformational and physicochemical properties of the oriT region, which
      facilitate relaxase-oriT recognition and initiation of nicking, MOB groups can be
      resolved with over 99% accuracy. We have shown that oriT structural properties
      are highly conserved and can be used to discriminate among MOB groups more
      efficiently than the oriT nucleotide sequence. The procedure for prediction of
      MOB groups and potential transfer range of plasmids was implemented using
      published data and is available at http://dnatools.eu/MOB/plasmid.html .

PMID- 29379099
TI  - The molecular mechanism of cell cycle arrest in the Bursa of Fabricius in chick
      exposed to Aflatoxin B 1.
AB  - Aflatoxin B1 shows potent hepatotoxic, carcinogenic, genotoxic, immunotoxic
      potential in humans and many species of animals. The aim of this study was to
      clarify the underlying mechanism of G0G1 phase and G2M phase arrest of cell cycle
      in the bursa of Fabricius in broilers exposed to dietary AFB1. 144 one-day-old
      healthy Cobb broilers were randomly divided into two groups and fed on control
      diet and 0.6 mg.Kg-1 AFB1 diet for 3 weeks. Histological observation showed that
      AFB1 induced the increase of nuclear debris and vacuoles in lymphoid follicle of
      BF. Results of flow cytometry studies showed that bursal cells arrested in G2M
      phase at 7 days of age and blocked in G0G1 phase at 14 and 21 days of age
      following exposure to AFB1. The qRT-PCR analysis indicated that cell cycle
      arrested in G2M phase via ATM-Chk2-cdc25-cyclin B/cdc2 pathway, and blocked in
      G0G1 phase through ATM-Chk2-cdc25-cyclin D/CDK6 pathway and ATM-Chk2-p21-cyclin
      D/CDK6 route. In a word, our results provided new insights that AFB1 diet induced
      G2M and G0G1 phase blockage of BF cells in different periods, and different
      pathways were activated in different arrested cell cycle phase.

PMID- 29379100
TI  - Social rank-associated stress vulnerability predisposes individuals to cocaine
      attraction.
AB  - Studies of personality have suggested that dissimilarities in ability to cope
      with stressful situations results in differing tendency to develop addictive
      behaviors. The present study used selectively bred stress-resilient, socially
      dominant (Dom) and stress-vulnerable, socially-submissive (Sub) mice to
      investigate the interaction between environmental stress and inbred
      predisposition to develop addictive behavior to cocaine. In a Conditioned Place
      Preference (CPP) paradigm using cocaine, Sub mice displayed an aversion to drug,
      whereas Dom mice displayed drug attraction. Following a 4-week regimen of Chronic
      Mild Stress (CMS), Sub mice in CPP displayed a marked increase (>400%) in cocaine
      attraction, whereas Dom mice did not differ in attraction from their non-stressed
      state. Examination of hippocampal gene expression revealed in Sub mice, exposure
      to external stimuli, stress or cocaine, increased CRH expression (>100%), which
      was evoked in Dom mice only by cocaine exposure. Further, stress-induced
      decreases in DRD1 (>60%) and DRD2 (>50%) expression in Sub mice differed markedly
      from a complete lack of change in Dom mice. From our findings, we propose that
      social stratification dictates vulnerability to stress-induced attraction that
      may lead to addiction via differential regulation of hippocampal response to
      dopaminergic input, which in turn may influence differing tendency to develop
      addictive behaviors.

PMID- 29379101
TI  - Extra-Mediterranean glacial refuges in barred and common grass snakes (Natrix
      helvetica, N. natrix).
AB  - Extra-Mediterranean glacial refugia of thermophilic biota, in particular in
      northern latitudes, are controversial. In the present study we provide genetic
      evidence for extra-Mediterranean refugia in two species of grass snake. The
      refuge of a widely distributed western European lineage of the barred grass snake
      (Natrix helvetica) was most likely located in southern France, outside the
      classical refuges in the southern European peninsulas. One genetic lineage of the
      common grass snake (N. natrix), distributed in Scandinavia, Central Europe and
      the Balkan Peninsula, had two distinct glacial refuges. We show that one was
      located in the southern Balkan Peninsula. However, Central Europe and Scandinavia
      were not colonized from there, but from a second refuge in Central Europe. This
      refuge was located in between the northern ice sheet and the Alpine glaciers of
      the last glaciation and most likely in a permafrost region. Another co
      distributed genetic lineage of N. natrix, now massively hybridizing with the
      aforementioned lineage, survived the last glaciation in a structured refuge in
      the southern Balkan Peninsula, according to the idea of 'refugia-within-refugia'.
      It reached Central Europe only very recently. This study reports for the first
      time the glacial survival of a thermophilic egg-laying reptile species in Central
      Europe.

PMID- 29379102
TI  - Multimodal imaging of buried optic nerve head drusen.

PMID- 29379103
TI  - Are we ready for genetic testing for primary open-angle glaucoma?
AB  - Following a dramatic reduction in the cost of genotyping technology in recent
      years, there have been significant advances in the understanding of the genetic
      basis of glaucoma. Glaucoma patients represent around a quarter of all outpatient
      activity in the UK hospital eye service and are a huge burden for the National
      Health Service. A potential benefit of genetic testing is personalised glaucoma
      management, allowing direction of our limited healthcare resources to the
      glaucoma patients who most need it. Our review aims to summarise recent
      discoveries in the field of glaucoma genetics and to discuss their potential
      clinical utility. While genome-wide association studies have now identified over
      ten genes associated with primary open-angle glaucoma (POAG), individually,
      variants in these genes are not predictive of POAG in populations. There are data
      suggesting some of these POAG variants are associated with conversion from ocular
      hypertension to POAG and visual field progression among POAG patients. However,
      these studies have not been replicated yet and such genetic testing is not
      currently justified in clinical care. In contrast, genetic testing for inherited
      early-onset disease in relatives of POAG patients with a known genetic mutation
      is of clear benefit; this can support either regular review to commence early
      treatment when the disease develops, or discharge from ophthalmology services of
      relatives who do not carry the mutation. Genetic testing for POAG at a population
      level is not currently justified.

PMID- 29379104
TI  - Slit lamps and lenses: a potential source of nosocomial infections?
AB  - PURPOSE: The aim of the study was to evaluate the bacterial contamination level
      of contact surfaces on slit lamps and the grip areas of lenses. METHODS: Within
      unannounced audits, two regions of the slit lamps (headrest and joystick),
      indirect ophthalmoscopy devices, and ultrasound probes were obtained with rayon
      tipped swab. Non-contact lenses used for indirect fundoscopy were pressed on
      RODAC (Replicate Organism Detection and Counting) plates. One hundred and eighty
      one surfaces were sampled. The total number of colony-forming units was assessed
      and bacterial species were identified. Spa-typing and antimicrobial
      susceptibility testing were performed from Staphylococcus aureus isolates.
      RESULTS: Among the total bacterial isolates from ophthalmological equipment
      (lenses: 51 of 78, slit lamps: 43 of 88, ophthalmoscopy helmets: 3 of 8,
      ultrasound probes: 2 of 7), coagulase-negative staphylococci (CNS) was most
      frequently found, followed by Micrococcus spp. (lenses vs. slit lamps: P < 0.001
      and P = 0.01, respectively). The bacterial contamination of lenses (76%) was
      significantly higher than that of slit lamps (54%) (P < 0.003). A significantly
      higher contamination with CNS was observed on lenses from residents vs. from
      consultants (78% vs. 35%, P = 0.01). A total of seven different spa-types of S.
      aureus were isolated. No correlation was found between S. aureus contamination of
      different ophthalmological equipments (Spearman's rank correlation coefficient,
      rho = 0.04, P = 0.75). Methicillin-resistant S. aureus was not detected.
      CONCLUSION: Bacterial species of the normal skin flora were isolated from the
      ophthalmological equipment. The bacterial contamination of the portable devices
      was significantly higher than that of slit lamps. Therefore, proper hygiene of
      the mobile instruments should be monitored in order to prevent transmission of
      bacteria in residents and consultants.

PMID- 29379105
TI  - Developmental Maturation and Alpha-1 Adrenergic Receptors-Mediated Gene
      Expression Changes in Ovine Middle Cerebral Arteries.
AB  - The Alpha Adrenergic Signaling Pathway is one of the chief regulators of
      cerebrovascular tone and cerebral blood flow (CBF), mediating its effects in the
      arteries through alpha1-adrenergic receptors (Alpha1AR). In the ovine middle
      cerebral artery (MCA), with development from a fetus to an adult, others and we
      have shown that Alpha1AR play a key role in contractile responses, vascular
      development, remodeling, and angiogenesis. Importantly, Alpha1AR play a
      significant role in CBF autoregulation, which is incompletely developed in a
      premature fetus as compared to a near-term fetus. However, the mechanistic
      pathways are not completely known. Thus, we tested the hypothesis that as a
      function of maturation and in response to Alpha1AR stimulation there is a
      differential gene expression in the ovine MCA. We conducted microarray analysis
      on transcripts from MCAs of premature fetuses (96-day), near-term fetuses (145
      day), newborn lambs, and non-pregnant adult sheep (2-year) following stimulation
      of Alpha1AR with phenylephrine (a specific agonist). We observed several genes
      which belonged to pro-inflammatory and vascular development/angiogenesis pathway
      significantly altered in all of the four age groups. We also observed age
      specific changes in gene expression-mediated by Alpha1AR stimulation in the
      different developmental age groups. These findings imply complex regulatory
      mechanisms of cerebrovascular development.

PMID- 29379106
TI  - Three-dimensional label-free imaging and analysis of Pinus pollen grains using
      optical diffraction tomography.
AB  - The structure of pollen grains is related to the reproductive function of the
      plants. Here, three-dimensional (3D) refractive index maps were obtained for
      individual conifer pollen grains using optical diffraction tomography (ODT). The
      3D morphological features of pollen grains from pine trees were investigated
      using measured refractive index maps, in which distinct substructures were
      clearly distinguished and analyzed. Morphological and physiochemical parameters
      of the pollen grains were quantified from the obtained refractive index (RI) maps
      and used to quantitatively study the interspecific differences of pollen grains
      from different strains. Our results demonstrate that ODT can assess the structure
      of pollen grains. This label-free and rapid 3D imaging approach may provide a new
      platform for understanding the physiology of pollen grains.

PMID- 29379107
TI  - Optical breakdown of solids by few-cycle laser pulses.
AB  - We show that a broadly accepted criterion of laser-induced breakdown in solids,
      defining the laser-breakdown threshold in terms of the laser fluence or laser
      intensity needed to generate a certain fraction of the critical electron density
      rc within the laser pulse, fails in the case of high-intensity few-cycle laser
      pulses. Such laser pulses can give rise to subcycle oscillations of electron
      density rho with peak rho values well above rhoc even when the total energy of
      the laser pulse is too low to induce a laser damage of material. The central idea
      of our approach is that, instead of the rho = rho c ratio, the laser-breakdown
      threshold connects to the total laser energy coupled to the electron subsystem
      and subsequently transferred to the crystal lattice. With this approach, as we
      show in this work, predictions of the physical model start to converge to the
      available experimental data.

PMID- 29379108
TI  - Graphene-catalyzed formation of C=N bonds via cleavage of C-C and N-O bonds in
      ethanol and nitrate under room temperature.
AB  - The cleavage of carbon-carbon bonds and the formation of carbon-nitrogen bonds
      play crucial roles in chemical synthesis. However, these reactions usually
      proceed at high temperature and involve multiple steps. Herein, we report an
      unusual and novel reaction catalyzed by graphene. The C-C bond in ethanol and the
      N-O bond in nitrate can be broken under room temperature, accompanied by the
      formation of the C=N bond. We demonstrate these reactions and elucidate their
      mechanisms by verifying that the product is silver cyanide which was formed when
      mixing a solution of silver nitrate and ethanol with graphene dispersion in
      ethanol at room temperature. The pivotal reason for the reaction is the formation
      of the precipitated silver cyanide. In a broader context, this discovery opens a
      significant new path for the breakage of the C-C bond in ethanol and the
      synthesis of nitriles under mild conditions. Also, the graphene was first
      reported as a catalyst for the room-temperature reaction.

PMID- 29379109
TI  - In-situ liquid cell transmission electron microscopy investigation on oriented
      attachment of gold nanoparticles.
AB  - Inside a liquid solution, oriented attachment (OA) is now recognized to be as
      important a pathway to crystal growth as other, more conventional growth
      mechanisms. However, the driving force that controls the occurrence of OA is
      still poorly understood. Here, using in-situ liquid cell transmission electron
      microscopy, we demonstrate the ligand-controlled OA of citrate-stabilized gold
      nanoparticles at atomic resolution. Our data reveal that particle pairs rotate
      randomly at a separation distance greater than twice the layer thickness of
      adsorbed ligands. In contrast, when the particles get closer, their ligands
      overlap and guide the rotation into a directional mode until they share a common
      {111} orientation, when a sudden contact occurs accompanied by the simultaneous
      expulsion of the ligands on this surface. First-principle calculations confirm
      that the lower ligand binding energy on {111} surfaces is the intrinsic reason
      for the preferential attachment at this facet, rather than on other low-index
      facets.

PMID- 29379110
TI  - Transaminase levels reflect disease severity in children ventilated for
      respiratory syncytial virus (RSV) bronchiolitis.
AB  - Bronchiolitis, often caused by respiratory syncytial virus (RSV), is the
      commonest cause of hospitalisation in infancy. Serum transaminases are sometimes
      raised in children with bronchiolitis. We tested the hypothesis that raised
      transaminases are associated with increased disease severity in children
      ventilated for bronchiolitis. Prospective observational cohort study of
      mechanically ventilated children with community-acquired RSV bronchiolitis.
      Alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured
      daily. Children with normal transaminases were compared with those with elevated
      levels. Over 11 consecutive winters, 556 children with RSV bronchiolitis were
      mechanically ventilated - 226 had comorbidities and therefore excluded; 313 of
      remaining 330 were under 2 years age; 305 had early transaminase measurements.
      57/305 (19%) had elevated transaminase (AST and/or ALT) levels. For the first
      time we show that duration of ventilation and length of admission were both
      significantly longer, and paediatric index of mortality and C-reactive protein
      higher, in those with elevated AST levels on admission (but not those with
      elevated ALT levels). Furthermore, transaminase elevations were transient,
      generally having normalised by seven days following admission. RSV bronchiolitis
      was more severe in children with early elevated AST levels and could be used
      early in the illness as a predictor for disease severity.

PMID- 29379111
TI  - New Antimicrobial Potential and Structural Properties of PAFB: A Cationic,
      Cysteine-Rich Protein from Penicillium chrysogenum Q176.
AB  - Small, cysteine-rich and cationic proteins with antimicrobial activity are
      produced by diverse organisms of all kingdoms and represent promising molecules
      for drug development. The ancestor of all industrial penicillin producing
      strains, the ascomycete Penicillium chryosgenum Q176, secretes the extensively
      studied antifungal protein PAF. However, the genome of this strain harbours at
      least two more genes that code for other small, cysteine-rich and cationic
      proteins with potential antifungal activity. In this study, we characterized the
      pafB gene product that shows high similarity to PgAFP from P. chrysogenum R42C.
      Although abundant and timely regulated pafB gene transcripts were detected, we
      could not identify PAFB in the culture broth of P. chrysogenum Q176. Therefore,
      we applied a P. chrysogenum-based expression system to produce sufficient amounts
      of recombinant PAFB to address unanswered questions concerning the structure and
      antimicrobial function. Nuclear magnetic resonance (NMR)-based analyses revealed
      a compact beta-folded structure, comprising five beta-strands connected by four
      solvent exposed and flexible loops and an "abcabc" disulphide bond pattern. We
      identified PAFB as an inhibitor of growth of human pathogenic moulds and yeasts.
      Furthermore, we document for the first time an anti-viral activity for two
      members of the small, cysteine-rich and cationic protein group from ascomycetes.

PMID- 29379112
TI  - Downregulation of glutamic acid decarboxylase in Drosophila TDP-43-null brains
      provokes paralysis by affecting the organization of the neuromuscular synapses.
AB  - Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that
      affects the motor system, comprised of motoneurons and associated glia.
      Accordingly, neuronal or glial defects in TDP-43 function provoke paralysis due
      to the degeneration of the neuromuscular synapses in Drosophila. To identify the
      responsible molecules and mechanisms, we performed a genome wide proteomic
      analysis to determine differences in protein expression between wild-type and TDP
      43-minus fly heads. The data established that mutant insects presented reduced
      levels of the enzyme glutamic acid decarboxylase (Gad1) and increased
      concentrations of extracellular glutamate. Genetic rescue of Gad1 activity in
      neurons or glia was sufficient to recuperate flies locomotion, synaptic
      organization and glutamate levels. Analogous recovery was obtained by treating
      TDP-43-null flies with glutamate receptor antagonists demonstrating that Gad1
      promotes synapses formation and prevents excitotoxicity. Similar suppression of
      TDP-43 provoked the downregulation of GAD67, the Gad1 homolog protein in human
      neuroblastoma cell lines and analogous modifications were observed in iPSC
      derived motoneurons from patients carrying mutations in TDP-43, uncovering
      conserved pathological mechanisms behind the disease.

PMID- 29379113
TI  - A regional assessment of cumulative impact mapping on Mediterranean coralligenous
      outcrops.
AB  - In the last decade, the 'Cumulative Pressure and Impact Assessment' (CPIA)
      approach emerged as a tool to map expected impacts on marine ecosystems. However,
      CPIA assumes a linear response of ecosystems to increasing level of cumulative
      pressure weighting sensitivity to different anthropogenic pressures through
      expert judgement. We applied CPIA to Mediterranean coralligenous outcrops over
      1000 km of the Italian coastline. Extensive field surveys were conducted to
      assess the actual condition of coralligenous assemblages at varying levels of
      human pressure. As pressure increased, a clear shift from bioconstructors to turf
      dominated assemblages was found. The linear model originally assumed for CPIA did
      not fit the actual relationship between expected cumulative impact versus
      assemblage degradation. A log-log model, instead, best fitted the data and
      predicted a different map of cumulative impact in the study area able to
      appreciate the whole range of impact scenarios. Hence, the relative importance of
      different drivers in explaining the observed pattern of degradation was not
      aligned with weights from the expert opinion. Such findings stress the need for
      more incisive efforts to collect empirical evidence on ecosystem-specific
      responses to human pressure in order to refine CPIA predictions.

PMID- 29379114
TI  - Comparison of focused cognitive training and portable "brain-games" on functional
      outcomes for vocational rehabilitation participants.
AB  - Cognitive remediation performed in a cognitive laboratory was compared with a
      sham control using portable brain games to study effects on vocational,
      neurocognitive, and functional outcomes for participants with psychotic disorders
      in vocational rehabilitation (VR). Seventy-seven participants (61% schizophrenia,
      39% other psychosis) in transitional (45.5%) or supported employment (54.5%) were
      randomly assigned to 6 months of portable cognitive-games (CG) or cognitive
      remediation (CR) plus a weekly goal-setting group, and evaluated during training,
      post-training and at 12 months. Overall rates of employment did not differ
      significantly at 12-month follow-up; however, VR + CG attained employment more
      rapidly during training. A significant time by condition interaction favored VR +
      CR on Quality of Life Total Score and Instrumental Functioning over 12 months.
      Neurocognitive outcomes favored VR + CR, particularly on attention. Training
      hours related significantly to neurocognitive improvement regardless of
      condition. No differences were found in training adherence despite portability
      for VR + CG. Results indicate that VR + CR had significantly greater effect than
      VR + CG on neurocognition and community functioning, but not on employment
      outcome. Job attainment rates during the training period revealed a potential
      advantage for portable training raising new questions concerning how cognitive
      remediation can be most effectively integrated with VR.

PMID- 29379115
TI  - Chemotherapy drugs cyclophosphamide, cisplatin and doxorubicin induce germ cell
      loss in an in vitro model of the prepubertal testis.
AB  - Long term survival rates for childhood cancers is steadily increasing, however
      cancer survivors can experience fertility problems as a consequence of
      chemotherapy treatment. This is particularly problematic for young boys, for whom
      no fertility preservation treatment is yet established. Here, we have determined
      the effects on prepubertal mouse testis of three commonly used chemotherapy
      drugs; cyclophosphamide (using its active metabolite phosphoramide mustard),
      cisplatin and doxorubicin, exposing testicular fragments to a clinically relevant
      range of concentrations in vitro. All three drugs induced a specific and highly
      significant loss of germ cells, including spermatogonial stem cells. In contrast,
      there was no significant effect on somatic cells, for either Sertoli or
      interstitial cells. Time course analysis of cleaved Caspase-3 expression showed a
      significant increase in apoptosis eight hours prior to a detectable decrease in
      germ cell numbers following exposure to phosphoramide mustard or cisplatin,
      although this pattern was not seen following doxorubicin-exposure. Moreover,
      analysis of DNA damage at 16 h showed increased gammaH2AX expression in response
      to all three drugs. Overall, results show that cisplatin, doxorubicin and
      cyclophosphamide all specifically induce loss of germ cells, including of
      spermatogonial stem cells, in the prepubertal mouse testis at concentrations
      relevant to human therapeutic exposures.

PMID- 29379117
TI  - Medial preoptic circuit induces hunting-like actions to target objects and prey.
AB  - As animals forage, they must obtain useful targets by orchestrating appropriate
      actions that range from searching to chasing, biting and carrying. Here, we
      reveal that neurons positive for the alpha subunit of Ca2+/calmodulin-dependent
      kinase II (CaMKIIalpha) in the medial preoptic area (MPA) that send projections
      to the ventral periaqueductal gray (vPAG) mediate these target-directed actions
      in mice. During photostimulation of the MPA-vPAG circuit, mice vigorously engaged
      with 3D objects and chased moving objects. When exposed to a cricket, they hunted
      down the prey and bit it to kill. By applying a head-mounted object control with
      timely photostimulation of the MPA-vPAG circuit, we found that MPA-vPAG circuit
      induced actions occurred only when the target was detected within the binocular
      visual field. Using this device, we successfully guided mice to navigate
      specified routes. Our study explains how the brain yields a strong motivation to
      acquire a target object along the continuum of hunting behavior.

PMID- 29379116
TI  - Insular cortex mediates approach and avoidance responses to social affective
      stimuli.
AB  - Social animals detect the affective states of conspecifics and utilize this
      information to orchestrate social interactions. In a social affective preference
      text in which experimental adult male rats could interact with either naive or
      stressed conspecifics, the experimental rats either approached or avoided the
      stressed conspecific, depending upon the age of the conspecific. Specifically,
      experimental rats approached stressed juveniles but avoided stressed adults.
      Inhibition of insular cortex, which is implicated in social cognition, and
      blockade of insular oxytocin receptors disrupted the social affective behaviors.
      Oxytocin application increased intrinsic excitability and synaptic efficacy in
      acute insular cortex slices, and insular oxytocin administration recapitulated
      the behaviors observed toward stressed conspecifics. Network analysis of c-Fos
      immunoreactivity in 29 regions identified functional connectivity between insular
      cortex, prefrontal cortex, amygdala and the social decision-making network. These
      results implicate insular cortex as a key component in the circuit underlying age
      dependent social responses to stressed conspecifics.

PMID- 29379118
TI  - Regulation of Kv2.1 channel inactivation by phosphatidylinositol 4,5
      bisphosphate.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane phospholipid that
      regulates the function of multiple ion channels, including some members of the
      voltage-gated potassium (Kv) channel superfamily. The PIP2 sensitivity of Kv
      channels is well established for all five members of the Kv7 family and for Kv1.2
      channels; however, regulation of other Kv channels by PIP2 remains unclear. Here,
      we investigate the effects of PIP2 on Kv2.1 channels by applying exogenous PIP2
      to the cytoplasmic face of excised membrane patches, activating muscarinic
      receptors (M1R), or depleting endogenous PIP2 using a rapamycin-translocated 5
      phosphatase (FKBP-Inp54p). Exogenous PIP2 rescued Kv2.1 channels from rundown and
      partially prevented the shift in the voltage-dependence of inactivation observed
      in inside-out patch recordings. Native PIP2 depletion by the recruitment of FKBP
      Insp54P or M1R activation in whole-cell experiments, induced a shift in the
      voltage-dependence of inactivation, an acceleration of the closed-state
      inactivation, and a delayed recovery of channels from inactivation. No
      significant effects were observed on the activation mechanism by any of these
      treatments. Our data can be modeled by a 13-state allosteric model that takes
      into account that PIP2 depletion facilitates inactivation of Kv2.1. We propose
      that PIP2 regulates Kv2.1 channels by interfering with the inactivation
      mechanism.

PMID- 29379119
TI  - The immunology of hepatocellular carcinoma.
AB  - In contrast to most other malignancies, hepatocellular carcinoma (HCC), which
      accounts for approximately 90% of primary liver cancers, arises almost
      exclusively in the setting of chronic inflammation. Irrespective of etiology, a
      typical sequence of chronic necroinflammation, compensatory liver regeneration,
      induction of liver fibrosis and subsequent cirrhosis often precedes
      hepatocarcinogenesis. The liver is a central immunomodulator that ensures organ
      and systemic protection while maintaining immunotolerance. Deregulation of this
      tightly controlled liver immunological network is a hallmark of chronic liver
      disease and HCC. Notably, immunotherapies have raised hope for the successful
      treatment of advanced HCC. Here we summarize the roles of specific immune cell
      subsets in chronic liver disease, with a focus on non-alcoholic steatohepatitis
      and HCC. We review new advances in immunotherapeutic approaches for the treatment
      of HCC and discuss the challenges posed by the immunotolerant hepatic environment
      and the dual roles of adaptive and innate immune cells in HCC.

PMID- 29379120
TI  - Structural and functional characterization of shaft, anchor, and tip proteins of
      the Mfa1 fimbria from the periodontal pathogen Porphyromonas gingivalis.
AB  - Very little is known about how fimbriae of Bacteroidetes bacteria are assembled.
      To shed more light on this process, we solved the crystal structures of the shaft
      protein Mfa1, the regulatory protein Mfa2, and the tip protein Mfa3 from the
      periodontal pathogen Porphyromonas gingivalis. Together these build up part of
      the Mfa1 fimbria and represent three of the five proteins, Mfa1-5, encoded by the
      mfa1 gene cluster. Mfa1, Mfa2 and Mfa3 have the same overall fold i.e., two beta
      sandwich domains. Upon polymerization, the first beta-strand of the shaft or tip
      protein is removed by indigenous proteases. Although the resulting void is
      expected to be filled by a donor-strand from another fimbrial protein, the
      mechanism by which it does so is still not established. In contrast, the first
      beta-strand in Mfa2, the anchoring protein, is firmly attached by a disulphide
      bond and is not cleaved. Based on the structural information, we created multiple
      mutations in P. gingivalis and analysed their effect on fimbrial polymerization
      and assembly in vivo. Collectively, these data suggest an important role for the
      C-terminal tail of Mfa1, but not of Mfa3, affecting both polymerization and
      maturation of downstream fimbrial proteins.

PMID- 29379121
TI  - A new method using Raman spectroscopy for in vivo targeted brain cancer tissue
      biopsy.
AB  - Modern cancer diagnosis requires histological, molecular, and genomic tumor
      analyses. Tumor sampling is often achieved using a targeted needle biopsy
      approach. Targeting errors and cancer heterogeneity causing inaccurate sampling
      are important limitations of this blind technique leading to non-diagnostic or
      poor quality samples, and the need for repeated biopsies pose elevated patient
      risk. An optical technology that can analyze the molecular nature of the tissue
      prior to harvesting could improve cancer targeting and mitigate patient risk.
      Here we report on the design, development, and validation of an in situ
      intraoperative, label-free, cancer detection system based on high wavenumber
      Raman spectroscopy. This optical detection device was engineered into a
      commercially available biopsy system allowing tumor analysis prior to tissue
      harvesting without disrupting workflow. Using a dual validation approach we show
      that high wavenumber Raman spectroscopy can detect human dense cancer with >60%
      cancer cells in situ during surgery with a sensitivity and specificity of 80% and
      90%, respectively. We also demonstrate for the first time the use of this system
      in a swine brain biopsy model. These studies set the stage for the clinical
      translation of this optical molecular imaging method for high yield and safe
      targeted biopsy.

PMID- 29379122
TI  - Rheumatoid arthritis patient antibodies highly recognize IL-2 in the immune
      response pathway involving IRF5 and EBV antigens.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a
      progressive joint damage due to largely unknown environmental factors acting in
      concert with risk alleles conferring genetic susceptibility. A major role has
      been attributed to viral infections that include past contacts with Epstein-Barr
      virus (EBV) and, more recently, to non-protein coding sequences of human
      endogenous retrovirus K (HERV-K) integrated in the human genome. Molecular
      mimicry between viral and self proteins is supposed to cause the loss of immune
      tolerance in predisposed hosts. There are evidences that anti-IL-2 antibodies
      (Abs) are present in subjects affected by autoimmune diseases and may be
      responsible for alterations in regulatory T cell responses. In this study, we
      evaluated the levels of Abs against IL-2, viral epitopes and interferon
      regulatory factor 5 (IRF5) in 140 RA patients and 137 healthy controls (HCs). Ab
      reactivity reached the highest levels for IRF5, EBV and IL-2 (56%, 44% and 39%,
      respectively) in RA with significantly lower values among HCs (7-9%, p < 0.0001),
      which suggests a possible cross-reaction between IRF5/EBV homologous antigens and
      shifts in T cell balance disrupted by anti-IL-2 Abs.

PMID- 29379123
TI  - A scalable approach to the computation of invariant measures for high-dimensional
      Markovian systems.
AB  - The Markovian invariant measure is a central concept in many disciplines.
      Conventional numerical techniques for data-driven computation of invariant
      measures rely on estimation and further numerical processing of a transition
      matrix. Here we show how the quality of data-driven estimation of a transition
      matrix crucially depends on the validity of the statistical independence
      assumption for transition probabilities. Moreover, the cost of the invariant
      measure computation in general scales cubically with the dimension - and is
      usually unfeasible for realistic high-dimensional systems. We introduce a method
      relaxing the independence assumption of transition probabilities that scales
      quadratically in situations with latent variables. Applications of the method are
      illustrated on the Lorenz-63 system and for the molecular dynamics (MD)
      simulation data of the alpha-synuclein protein. We demonstrate how the
      conventional methodologies do not provide good estimates of the invariant measure
      based upon the available alpha-synuclein MD data. Applying the introduced
      approach to these MD data we detect two robust meta-stable states of alpha
      synuclein and a linear transition between them, involving transient formation of
      secondary structure, qualitatively consistent with previous purely experimental
      reports.

PMID- 29379124
TI  - Bacillus licheniformis normalize the ileum microbiota of chickens infected with
      necrotic enteritis.
AB  - Necrotic enteritis (NE) is a severe intestinal disease, which can change gut
      microbiota and result in a high cost for the poultry industry worldwide. However,
      little is known regarding how the gut microbiota of NE chicken ileum are changed
      by Bacillus licheniformis. This study was conducted to investigate how ileum
      microbiota structure was changed by B. licheniformis in broiler chickens
      challenged with Clostridium perfringens-induced NE through Illumina MiSeq
      sequencing. The broilers were randomly separated into four groups: the negative
      control group (NC), the positive control group (PC), the fishmeal and coccidia
      group (FC), and the PC group supplied with feed containing B. licheniformis (BL).
      Compared to the PC and FC, alpha diversity, beta diversity, and the bacterial
      taxa of the ileum microbiota were more similar in BL and NC. Some genera, which
      were related to the NE control, became insignificant in BL with NC, such as
      Lactobacillus, Lactococcus, Bacteroides, Ruminococcus and Helicobacter. The
      PICRUSt analysis revealed that a tumour suppressor gene, p53, which was
      negatively correlated with Helicobacter, was enriched in the BL group. Our
      findings showed that the ileum microbiota disorder caused by NE in chickens was
      normalized by dietary B. licheniformis supplementation.

PMID- 29379125
TI  - Novel insights into the mechanism of well-ordered assembly of bacterial flagellar
      proteins in Salmonella.
AB  - The FliI ATPase of the flagellar type III protein export apparatus forms the
      FliH2FliI complex along with its regulator FliH. The FliH2FliI complex is
      postulated to bring export substrates from the cytoplasm to the docking platform
      made of FlhA and FlhB although not essential for flagellar protein export. Here,
      to clarify the role of the FliH2FliI complex in flagellar assembly, we analysed
      the effect of FliH and FliI deletion on flagellar protein export and assembly.
      The hook length was not controlled properly in the ?fliH-fliI flhB(P28T) mutant
      compared to wild-type cells, whose hook length is controlled to about 55 nm
      within 10% error. The FlhA(F459A) mutation increased the export level of the hook
      protein FlgE and the ruler protein FliK by about 10-fold and 3-fold,
      respectively, and improved the hook length control in the absence of FliH and
      FliI. However, the ?fliH-fliI flhB(P28T) flhA(F459A) mutant did not produce
      flagellar filaments efficiently, and a large amount of flagellin monomers were
      leaked out into the culture media. Neither the hook length control nor flagellin
      leakage was affected by the FlhB(P28T) and FlhA(F459A) mutations. We will discuss
      a hierarchical protein export mechanism of the bacterial flagellum.

PMID- 29379126
TI  - Edaphic characterization and plant zonation in the Qaidam Basin, Tibetan Plateau.
AB  - This paper presents a study of edaphic characteristics and their relationship
      with plant distribution in the Qaidam Basin, Tibetan Plateau, and establishes a
      distribution model for plants in sandy gravel Gobi to dry salt lake areas. All of
      the communities in the study area were dominated by plants with strong saline
      alkaline tolerance. In this area, salts appeared to migrate to the surface; the
      surface soil was striped, and the salt distribution varied from sandy gravel Gobi
      to dry salt lake areas. The salt composition mainly consisted of NaCl in the
      surface crust. In the subsurface layers, the salt composition was dominated by
      Ca2+, Cl- and SO42-. The type of vegetation at the study site can be divided into
      two categories: salt-tolerant vegetation and weakly salt-tolerant vegetation. The
      salt-tolerant vegetation is influenced by Na+, Cl-, and the salinity. The soil of
      these vegetation communities had a higher salt and Na+ concentration and a lower
      Ca2+ and K+ concentration. The weakly salt-tolerant vegetation is mainly affected
      by the Ca2+/Na+ and K+/Na+ ratios. Based on the above results, a vegetation
      distribution model for saline lakes on the inland plateau was established.

PMID- 29379128
TI  - Injection locking at 2f of spin torque oscillators under influence of thermal
      noise.
AB  - Integration of Spin Torque Nano-Oscillators STNO's in conventional microwave
      circuits means that the devices have to meet certain specifications. One of the
      most important criteria is the phase noise, being the key parameter to evaluate
      the performance and define possible applications. Phase locking several
      oscillators together has been suggested as a possible means to decrease phase
      noise and consequently, the linewidth. In this work we present experiments,
      numerical simulations and an analytic model to describe the effects of thermal
      noise in the injection locking of a tunnel junction based STNO. The analytics
      show the relation of the intrinsic parameters of the STNO with the phase noise
      level, opening the path to tailor the spectral characteristics by the magnetic
      configuration. Experiments and simulations demonstrate that in the in-plane
      magnetized structure, while the frequency is locked, much higher reference
      currents are needed to reduce the noise by phase locking. Moreover, our analysis
      shows that it is possible to control the phase noise by the reference microwave
      current (IRF) and that it can be further reduced by increasing the bias current
      (IDC) of the oscillator, keeping the reference current in feasible limits for
      applications.

PMID- 29379127
TI  - PlanHab Study: Consequences of combined normobaric hypoxia and bed rest on
      adenosine kinetics.
AB  - Adenosine plays a role in the energy supply of cells and provokes differential,
      hormone-like functions in circulating cells and various tissues. Its release is
      importantly regulated by oxygen tension. This renders adenosine and its kinetics
      interesting to investigate in humans subjected to low oxygen conditions.
      Especially for space exploration scenarios, hypoxic conditions - together with
      reduced gravity - represent two foreseen living conditions when planning manned
      long-duration space missions or planetary habitats. The PlanHab study
      investigated microgravity through inactivity in bed rest and normobaric hypoxia
      to examine their independent or combined effect on adenosine and its kinetics.
      Healthy male subjects (n = 14) completed three 21-day interventions: hypoxic bed
      rest (HBR); hypoxic ambulatory confinement (HAMB); normoxic bed rest (NBR). The
      interventions were separated by 4 months. Our hypothesis of a hypoxia-triggered
      increase in adenosine was confirmed in HAMB but unexpectedly also in NBR.
      However, the highest adenosine levels were noted following HBR. Furthermore, the
      percentage of hemolysis was elevated in HBR whereas endothelial integrity markers
      stayed low in all three interventions. In summary, these data suggest that
      neocytolysis accounts for these effects while we could reduce evidence for
      microcirculatory changes.

PMID- 29379129
TI  - Neural correlates underlying change in state self-esteem.
AB  - State self-esteem, the momentary feeling of self-worth, functions as a sociometer
      involved in maintenance of interpersonal relations. How others' appraisal is
      subjectively interpreted to change state self-esteem is unknown, and the neural
      underpinnings of this process remain to be elucidated. We hypothesized that
      changes in state self-esteem are represented by the mentalizing network, which is
      modulated by interactions with regions involved in the subjective interpretation
      of others' appraisal. To test this hypothesis, we conducted task-based and
      resting-state fMRI. Participants were repeatedly presented with their
      reputations, and then rated their pleasantness and reported their state self
      esteem. To evaluate the individual sensitivity of the change in state self-esteem
      based on pleasantness (i.e., the subjective interpretation of reputation), we
      calculated evaluation sensitivity as the rate of change in state self-esteem per
      unit pleasantness. Evaluation sensitivity varied across participants, and was
      positively correlated with precuneus activity evoked by reputation rating.
      Resting-state fMRI revealed that evaluation sensitivity was positively correlated
      with functional connectivity of the precuneus with areas activated by negative
      reputation, but negatively correlated with areas activated by positive
      reputation. Thus, the precuneus, as the part of the mentalizing system, serves as
      a gateway for translating the subjective interpretation of reputation into state
      self-esteem.

PMID- 29379130
TI  - DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator
      of intestinal cell proliferation and tumorigenesis.
AB  - The ERK signalling pathway regulates key cell fate decisions in the intestinal
      epithelium and is frequently dysregulated in colorectal cancers (CRCs).
      Variations in the dynamics of ERK activation can induce different biological
      outcomes and are regulated by multiple mechanisms, including activation of
      negative feedback loops involving transcriptional induction of dual-specificity
      phosphatases (DUSPs). We have found that the nuclear ERK-selective phosphatase
      DUSP5 is downregulated in colorectal tumours and cell lines, as previously
      observed in gastric and prostate cancer. The DUSP5 promoter is methylated in a
      subset of CRC cell lines and primary tumours, particularly those with a CpG
      island methylator phenotype (CIMP). However, this epigenetic change alone could
      not account for reduced DUSP5 expression in CRC cells. Functionally, DUSP5
      depletion failed to alter ERK signalling or proliferation in CRC cell lines, and
      its transgenic overexpression in the mouse intestine had minimal impact on normal
      intestinal homeostasis or tumour development. Our results suggest that DUSP5
      plays a limited role in regulating ERK signalling associated with the growth of
      colorectal tumours, but that methylation the DUSP5 gene promoter can serve as an
      additional means of identifying CIMP-high colorectal cancers.

PMID- 29379131
TI  - Diversity Modification and Structure-Activity Relationships of Two Natural
      Products 1beta-hydroxy Alantolactone and Ivangustin as Potent Cytotoxic Agents.
AB  - Sesquiterpene lactones (STLs) are a class of plant secondary metabolites widely
      found in nature with potent antitumor activities. In this work, two isolated STLs
      1beta-hydroxy alantolactone (1) and ivangustin (2) were derivatized through
      diversity-oriented strategy, and in vitro cytotoxic activity assessments were
      conducted against six cell lines including HeLa, PC-3, HEp-2, HepG2, CHO and
      HUVEC. The cytotoxic structure-activity relationship showed that the double bond
      between C5 and C6 was beneficial to improve activity; C1-OH oxidized derivatives
      showed a slight stronger activity, comparable to the positive drug etoposide (VP
      16). Yet, C1-OH esterified derivatives decreased the potency which were different
      from those of 1-O-acetylbritannilactone (ABL) reported previously by us, and C13
      methylene reductive and spiro derivatives resulted in almost complete ablation of
      cytotoxic activity. Mechanistic basis of cytotoxicity of the representative
      compound 1i was assayed to relate with apoptosis and cell cycle arrest.
      Furthermore, 1i inhibited TNF-alpha-induced canonical NF-kappaB signaling in PC-3
      cells. Molecular modeling studies exhibited additional hydrogen bond interaction
      between 1i and the residue Lys37 of p65, indicating that 1i could form covalent
      protein adducts with Cys38 on p65.

PMID- 29379132
TI  - MRI/Fluorescence bimodal amplification system for cellular GSH detection and
      tumor cell imaging based on manganese dioxide nanosheet.
AB  - Here, we report a novel magnetic resonance imaging (MRI)/fluorescence bimodal
      amplification platform for the detection of glutathione (GSH) on the basis of
      redoxable manganese dioxide (MnO2) nanosheets, which can be readily applied as a
      DNA nanocarrier, fluorescence quencher, and intracellular GSH-activated MRI
      contrast agent. The binding of aptamers that absorbed on the MnO2 nanosheets to
      their target can facilitating the endocytosis of target-nanoprobes. Once
      endocytosed, the MnO2 nanosheets can react with cellular GSH, resulting in the
      disintegration of nanosheets to generate plenty of Mn2+ ions for MRI and releases
      the primers which were adsorbed on the MnO2 nanosheets. Then the rolling circle
      amplification (RCA) reaction was initiated to amplify the fluorescence signal. In
      addition, after treatment with GSH, the MnO2 nanosheets were reduced and then
      most of the fluorescence was recovered. Therefore, this MnO2 nanoprobe exhibits
      excellent selectivity, suggesting a potential detection platform for analyzing
      the glutathione level in cells.

PMID- 29379133
TI  - Critical aggregation concentration for the formation of early Amyloid-beta (1-42)
      oligomers.
AB  - The oligomers formed during the early steps of amyloid aggregation are thought to
      be responsible for the neurotoxic damage associated with Alzheimer's disease. It
      is therefore of great interest to characterize this early aggregation process and
      the aggregates formed, especially for the most significant peptide in amyloid
      fibrils, Amyloid-beta(1-42) (Abeta42). For this purpose, we directly monitored
      the changes in size and concentration of initially monomeric Abeta42 samples,
      using Fluorescence Correlation Spectroscopy. We found that Abeta42 undergoes
      aggregation only when the amount of amyloid monomers exceeds the critical
      aggregation concentration (cac) of about 90 nM. This spontaneous, cooperative
      process resembles surfactants self-assembly and yields stable micelle-like
      oligomers whose size (~50 monomers, R h ~ 7-11 nm) and elongated shape are
      independent of incubation time and peptide concentration. These findings reveal
      essential features of in vitro amyloid aggregation, which may illuminate the
      complex in vivo process.

PMID- 29379134
TI  - Plant genetics: Parasites plant microRNAs in the host.

PMID- 29379135
TI  - Cloud computing for genomic data analysis and collaboration.
AB  - Next-generation sequencing has made major strides in the past decade. Studies
      based on large sequencing data sets are growing in number, and public archives
      for raw sequencing data have been doubling in size every 18 months. Leveraging
      these data requires researchers to use large-scale computational resources. Cloud
      computing, a model whereby users rent computers and storage from large data
      centres, is a solution that is gaining traction in genomics research. Here, we
      describe how cloud computing is used in genomics for research and large-scale
      collaborations, and argue that its elasticity, reproducibility and privacy
      features make it ideally suited for the large-scale reanalysis of publicly
      available archived data, including privacy-protected data.

PMID- 29379136
TI  - A novel mouse model carrying a human cytoplasmic dynein mutation shows motor
      behavior deficits consistent with Charcot-Marie-Tooth type 2O disease.
AB  - Charcot-Marie-Tooth disease (CMT) is a peripheral neuromuscular disorder in which
      axonal degeneration causes progressive loss of motor and sensory nerve function.
      The loss of motor nerve function leads to distal muscle weakness and atrophy,
      resulting in gait problems and difficulties with walking, running, and balance. A
      mutation in the cytoplasmic dynein heavy chain (DHC) gene was discovered to cause
      an autosomal dominant form of the disease designated Charcot-Marie-Tooth type 2 O
      disease (CMT2O) in 2011. The mutation is a single amino acid change of histidine
      into arginine at amino acid 306 (H306R) in DHC. In order to understand the onset
      and progression of CMT2, we generated a knock-in mouse carrying the corresponding
      CMT2O mutation (H304R/+). We examined H304R/+ mouse cohorts in a 12-month
      longitudinal study of grip strength, tail suspension, and rotarod assays. H304R/+
      mice displayed distal muscle weakness and loss of motor coordination phenotypes
      consistent with those of individuals with CMT2. Analysis of the gastrocnemius of
      H304R/+ male mice showed prominent defects in neuromuscular junction (NMJ)
      morphology including reduced size, branching, and complexity. Based on these
      results, the H304R/+ mouse will be an important model for uncovering functions of
      dynein in complex organisms, especially related to CMT onset and progression.

PMID- 29379137
TI  - Aerobic Exercise for a Duration of 90 min or Longer Per Week may Reduce the
      Atherogenic Index of Plasma.
AB  - The correlation between the weekly duration of aerobic exercise and atherogenic
      index of plasma (AIP) is still unknown. A cross-sectional study was conducted
      involving 27,827 middle-aged Chinese men who had health examinations in our
      hospital. The correlation between the duration of moderate-intensity aerobic
      exercise and AIP was determined. The mean AIP levels were 0.1166 +/- 0.34475,
      0.1167 +/- 0.32637, and 0.0765 +/- 0.32872 in the non-exercise (PA1), occasional
      exercise (PA2), and frequent exercise groups (PA3), respectively. Significantly
      higher AIP levels were observed in the PA1 and PA2 groups than the PA3 group,
      while no significant difference existed between the PA1 and PA2 groups. Physical
      activity significantly reduced the AIP after adjustment for age, body mass index,
      diastolic blood pressure, and fasting blood glucose and uric acid levels. In
      addition, the percentage of the population at high risk for atherosclerosis (AIP
      >= 0.21) was significantly lower in the PA3 group than the PA1 and PA2 groups.
      Moderate-intensity aerobic exercise at a weekly duration of 90 min or longer is
      associated with the reduction of AIP among middle-aged men in southeastern China.

PMID- 29379138
TI  - Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand
      metabolism rather than chemical source is the stronger predictor of outcome.
AB  - The aryl hydrocarbon receptor (AHR) offers a compelling target to modulate the
      immune system. AHR agonists alter adaptive immune responses, but the consequences
      differ across studies. We report here the comparison of four agents representing
      different sources of AHR ligands in mice infected with influenza A virus (IAV):
      TCDD, prototype exogenous AHR agonist; PCB126, pollutant with documented human
      exposure; ITE, novel pharmaceutical; and FICZ, degradation product of tryptophan.
      All four compounds diminished virus-specific IgM levels and increased the
      proportion of regulatory T cells. TCDD, PCB126 and ITE, but not FICZ, reduced
      virus-specific IgG levels and CD8+ T cell responses. Similarly, ITE, PCB126, and
      TCDD reduced Th1 and Tfh cells, whereas FICZ increased their frequency. In Cyp1a1
      deficient mice, all compounds, including FICZ, reduced the response to IAV.
      Conditional Ahr knockout mice revealed that all four compounds require AHR within
      hematopoietic cells. Thus, differences in the immune response to IAV likely
      reflect variances in quality, magnitude, and duration of AHR signaling. This
      indicates that binding affinity and metabolism may be stronger predictors of
      immune effects than a compound's source of origin, and that harnessing AHR will
      require finding a balance between dampening immune-mediated pathologies and
      maintaining sufficient host defenses against infection.

PMID- 29379139
TI  - Local control of intracellular microtubule dynamics by EB1 photodissociation.
AB  - End-binding proteins (EBs) are adaptors that recruit functionally diverse
      microtubule plus-end-tracking proteins (+TIPs) to growing microtubule plus ends.
      To test with high spatial and temporal accuracy how, when and where +TIP
      complexes contribute to dynamic cell biology, we developed a photo-inactivated
      EB1 variant (pi-EB1) by inserting a blue-light-sensitive protein-protein
      interaction module between the microtubule-binding and +TIP-binding domains of
      EB1. pi-EB1 replaces endogenous EB1 function in the absence of blue light. By
      contrast, blue-light-mediated pi-EB1 photodissociation results in rapid +TIP
      complex disassembly, and acutely and reversibly attenuates microtubule growth
      independent of microtubule end association of the microtubule polymerase CKAP5
      (also known as ch-TOG and XMAP215). Local pi-EB1 photodissociation allows
      subcellular control of microtubule dynamics at the second and micrometre scale,
      and elicits aversive turning of migrating cancer cells. Importantly, light
      mediated domain splitting can serve as a template to optically control other
      intracellular protein activities.

PMID- 29379140
TI  - Operation of a P300-based brain-computer interface in patients with Duchenne
      muscular dystrophy.
AB  - A brain-computer interface (BCI) or brain-machine interface is a technology that
      enables the control of a computer and other external devices using signals from
      the brain. This technology has been tested in paralysed patients, such as those
      with cervical spinal cord injuries or amyotrophic lateral sclerosis, but it has
      not been tested systematically in Duchenne muscular dystrophy (DMD), which is a
      severe type of muscular dystrophy due to the loss of dystrophin and is often
      accompanied by progressive muscle weakness and wasting. Here, we investigated the
      efficacy of a P300-based BCI for patients with DMD. Eight bedridden patients with
      DMD and eight age- and gender-matched able-bodied controls were instructed to
      input hiragana characters. We used a region-based, two-step P300-based BCI with
      green/blue flicker stimuli. EEG data were recorded, and a linear discriminant
      analysis distinguished the target from other non-targets. The mean online
      accuracy of inputted characters (accuracy for the two-step procedure) was 71.6%
      for patients with DMD and 80.6% for controls, with no significant difference
      between the patients and controls. The P300-based BCI was operated successfully
      by individuals with DMD in an advanced stage and these findings suggest that this
      technology may be beneficial for patients with this disease.

PMID- 29379141
TI  - Communication between the leaflets of asymmetric membranes revealed from coarse
      grain molecular dynamics simulations.
AB  - We use coarse-grain molecular simulations to investigate the structural and
      dynamics differences between an asymmetric and a symmetrical membrane, both
      containing beta barrel transmembrane proteins. We find in where the dynamics of
      the two leaflets differ greatly, the slowest leaflet dominates the structural
      effects and importance of protein-lipid interactions.

PMID- 29379142
TI  - Erythrocyte folate, serum vitamin B12, and hearing loss in the 2003-2004 National
      Health And Nutrition Examination Survey (NHANES).
AB  - BACKGROUND/OBJECTIVES: Studies based on food frequency questionnaires suggest
      that folate and vitamin B12 intake could protect against hearing loss. We
      investigated whether erythrocyte folate and serum vitamin B12 levels are
      independently associated with hearing loss in humans. SUBJECTS/METHODS:
      Participants in the 2003-2004 US National Health and Nutrition Examination Survey
      who had data on hearing, folate, and vitamin B12 levels were included. Pure-tone
      average (PTA) at 0.5, 1.0, 2.0, and 4.0 kHz was computed for each ear. We used
      weighted logistic regression to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs) for the relation between quartiles of folate and vitamin B12, and
      hearing loss (present if PTA > 25 dB in either ear and absent if PTA <= 25 dB in
      both ears). RESULTS: Participants (n = 1149) were 20-69 (mean 42) years old and
      16.4% had hearing loss in at least one ear. Our data suggest a U-shaped
      relationship between folate and hearing loss. Compared to the 1st quartile, the
      ORs (95% CIs) for hearing loss were 0.87 (0.49-1.53), 0.70 (0.49-1.00), and 1.08
      (0.61-1.94) for the 2nd, 3rd, and 4th quartile of erythrocyte folate in analyses
      adjusted for age, sex, vitamin B12, smoking, alcohol use, body mass index,
      race/ethnicity, exposure to noise, income, and education. Although we observed
      inverse associations between vitamin B12 and hearing loss, the associations were
      not statistically significant (P > 0.05). CONCLUSIONS: Our data show a U-shaped
      relationship between erythrocyte folate levels and hearing loss, suggesting a
      need to evaluate whether optimizing blood folate levels could prevent hearing
      loss.

PMID- 29379143
TI  - Effect of wine on carotid atherosclerosis in type 2 diabetes: a 2-year randomized
      controlled trial.
AB  - BACKGROUND/OBJECTIVES: The progression of carotid-plaque volume in patients with
      type 2 diabetes is common. Previous observational studies showed an association
      between moderate alcohol and reduced risk of coronary disease. We examined
      whether consuming moderate wine affects the progression of carotid
      atherosclerosis. SUBJECTS/METHODS: In the CASCADE (CArdiovaSCulAr Diabetes and
      Ethanol), a 2-year randomized controlled trial, we randomized abstainers with
      type 2 diabetes were to drink 150 ml of either red wine, white wine, or water,
      provided for 2 years. In addition, groups were guided to maintain a Mediterranean
      diet. We followed 2-year changes in carotid total plaque volume (carotid-TPV) and
      carotid vessel wall volume (carotid-VWV), using three-dimensional ultrasound.
      RESULTS: Carotid images were available from 174 of the 224 CASCADE participants
      (67% men; age = 59 yr; HbA1C = 6.8%). Forty-five percent had detectable plaque at
      baseline. After 2 years, no significant progression in carotid-TPV was observed
      (water, -1.4 (17.0) mm3, CI (-2.7, 5.5), white-wine, -1.2 (16.9) mm3, CI (-3.8,
      6.2), red wine, -1.3 (17.6) mm3, CI (-3.4, 6.0; p = 0.9 between groups)). In post
      hoc analysis, we divided the 78 participants with detectable baseline carotid
      plaque into tertiles. Those with the higher baseline plaque burden, whom were
      assigned to drink wine, reduced their plaque volume significantly after 2 years,
      as compared to baseline. Two-year reductions in Apo(B)/Apo(A) ratio(s) were
      independently associated with regression in carotid-TPV (beta = 0.4; p < 0.001).
      Two-year decreases in systolic blood pressure were independently associated with
      regression in carotid-VWV (beta = 0.2; p = 0.005). CONCLUSIONS: No progression in
      carotid-TPV was observed. In subgroup analyses, those with the greatest plaque
      burden assigned to drink wine may have had a small regression of plaque burden.

PMID- 29379144
TI  - Carbohydrate and fiber intake and the risk of premenstrual syndrome.
AB  - BACKGROUND/OBJECTIVES: Women with premenstrual syndrome (PMS) are encouraged to
      reduce sugar and increase fiber intake to reduce symptoms. However, research
      supporting these recommendations is limited, and their role in PMS development is
      unclear. This study examines the relation between carbohydrate and fiber intake
      and the risk of PMS nested within the prospective Nurses' Health Study II cohort.
      SUBJECTS/METHODS: Carbohydrate and fiber intake were assessed at baseline and
      three additional times during follow up by food frequency questionnaire. Incident
      cases of PMS were identified by self-reported PMS diagnosis during 14 years of
      follow up and validated by supplemental questionnaire (n = 1234). Women were
      classified as controls if they did not report PMS diagnosis during follow up and
      confirmed minimal or no premenstrual symptoms (n = 2426). We estimated relative
      risks (RR) and 95% confidence intervals (CI) using multivariable logistic
      regression. RESULTS: Total carbohydrate intake 2-4 years before reference year
      was not associated with PMS development (RR quintile 5 versus 1 = 0.99; 95% CI =
      0.74-1.33). Intakes of specific carbohydrates or fibers were not associated with
      PMS development, except maltose. Adjusting for body mass index, smoking, and
      other factors, women with the highest maltose intake (median = 3.0 g/day) had a
      RR of 1.45 (95% CI = 1.11-1.88) compared to those with the lowest intake (median
      = 1.2 g/day). CONCLUSIONS: Overall, carbohydrate and fiber consumption was not
      associated with risk of PMS. As this is the first study to suggest that maltose
      may be associated with PMS development, further replication is needed.

PMID- 29379145
TI  - Just the tip of the iceberg: difficulties in assessing and managing extreme
      obesity in routine clinical care.
AB  - As obesity prevalence increases worldwide, healthcare professionals are often
      faced with challenging cases associated with massive obesity. A 33-year-old woman
      (weight 342 kg, body mass index = 100 kg/m2) presented with respiratory failure,
      limb edema and ascites. Abdominal CT scan became feasible after initial weight
      loss and showed a large pelvic mass in contact with the left ovary. The surgical
      removal performed despite a high-risk profile led to the diagnosis of a giant
      mucinous borderline tumor whose growth was due to delayed care and responsible
      for multiple severe complications: sepsis, anemia, esophagitis, constipation,
      anorexia due to mechanical compression, undernutrition, sarcopenia and lower limb
      edema contributing to a severe disability. After 7 months under specialized care,
      her weight decreased to 180 kg, complications were treated and disability
      improved. This case, showing that, despite barriers, a multidisciplinary approach
      makes quality of care possible even in massively obese patients, is an
      educational example to reduce stigma.

PMID- 29379146
TI  - Antenna network.

PMID- 29379148
TI  - Mixing genomes alters nuclear architecture.

PMID- 29379147
TI  - Adapt to plants.

PMID- 29379149
TI  - Evolutionary dynamics of 3D genome architecture following polyploidization in
      cotton.
AB  - The formation of polyploids significantly increases the complexity of
      transcriptional regulation, which is expected to be reflected in sophisticated
      higher-order chromatin structures. However, knowledge of three-dimensional (3D)
      genome structure and its dynamics during polyploidization remains poor. Here, we
      characterize 3D genome architectures for diploid and tetraploid cotton, and find
      the existence of A/B compartments and topologically associated domains (TADs). By
      comparing each subgenome in tetraploids with its extant diploid progenitor, we
      find that genome allopolyploidization has contributed to the switching of A/B
      compartments and the reorganization of TADs in both subgenomes. We also show that
      the formation of TAD boundaries during polyploidization preferentially occurs in
      open chromatin, coinciding with the deposition of active chromatin modification.
      Furthermore, analysis of inter-subgenomic chromatin interactions has revealed the
      spatial proximity of homoeologous genes, possibly associated with their
      coordinated expression. This study advances our understanding of chromatin
      organization in plants and sheds new light on the relationship between 3D genome
      evolution and transcriptional regulation.

PMID- 29379150
TI  - RNA-directed DNA methylation involves co-transcriptional small-RNA-guided slicing
      of polymerase V transcripts in Arabidopsis.
AB  - Small RNAs regulate chromatin modifications such as DNA methylation and gene
      silencing across eukaryotic genomes. In plants, RNA-directed DNA methylation
      (RdDM) requires 24-nucleotide small interfering RNAs (siRNAs) that bind to
      ARGONAUTE 4 (AGO4) and target genomic regions for silencing. RdDM also requires
      non-coding RNAs transcribed by RNA polymerase V (Pol V) that probably serve as
      scaffolds for binding of AGO4-siRNA complexes. Here, we used a modified global
      nuclear run-on protocol followed by deep sequencing to capture Pol V nascent
      transcripts genome-wide. We uncovered unique characteristics of Pol V RNAs,
      including a uracil (U) common at position 10. This uracil was complementary to
      the 5' adenine found in many AGO4-bound 24-nucleotide siRNAs and was eliminated
      in a siRNA-deficient mutant as well as in the ago4/6/9 triple mutant, suggesting
      that the +10 U signature is due to siRNA-mediated co-transcriptional slicing of
      Pol V transcripts. Expression of wild-type AGO4 in ago4/6/9 mutants was able to
      restore slicing of Pol V transcripts, but a catalytically inactive AGO4 mutant
      did not correct the slicing defect. We also found that Pol V transcript slicing
      required SUPPRESSOR OF TY INSERTION 5-LIKE (SPT5L), an elongation factor whose
      function is not well understood. These results highlight the importance of Pol V
      transcript slicing in RNA-mediated transcriptional gene silencing, which is a
      conserved process in many eukaryotes.

PMID- 29379151
TI  - Dynamic thylakoid stacking regulates the balance between linear and cyclic
      photosynthetic electron transfer.
AB  - Upon transition of plants from darkness to light the initiation of photosynthetic
      linear electron transfer (LET) from H2O to NADP+ precedes the activation of CO2
      fixation, creating a lag period where cyclic electron transfer (CET) around
      photosystem I (PSI) has an important protective role. CET generates DeltapH
      without net reduced NADPH formation, preventing overreduction of PSI via
      regulation of the cytochrome b 6 f (cytb 6 f) complex and protecting PSII from
      overexcitation by inducing non-photochemical quenching. The dark-to-light
      transition also provokes increased phosphorylation of light-harvesting complex II
      (LHCII). However, the relationship between LHCII phosphorylation and regulation
      of the LET/CET balance is not understood. Here, we show that the dark-to-light
      changes in LHCII phosphorylation profoundly alter thylakoid membrane architecture
      and the macromolecular organization of the photosynthetic complexes, without
      significantly affecting the antenna size of either photosystem. The grana
      diameter and number of membrane layers per grana are decreased in the light while
      the number of grana per chloroplast is increased, creating a larger contact area
      between grana and stromal lamellae. We show that these changes in thylakoid
      stacking regulate the balance between LET and CET pathways. Smaller grana promote
      more efficient LET by reducing the diffusion distance for the mobile electron
      carriers plastoquinone and plastocyanin, whereas larger grana enhance the
      partition of the granal and stromal lamellae plastoquinone pools, enhancing the
      efficiency of CET and thus photoprotection by non-photochemical quenching.

PMID- 29379152
TI  - The goat grass genome's role in wheat improvement.

PMID- 29379154
TI  - A Gneato nuclear genome.

PMID- 29379153
TI  - Enabling the water-to-land transition.

PMID- 29379156
TI  - UVR8 interacts with WRKY36 to regulate HY5 transcription and hypocotyl elongation
      in Arabidopsis.
AB  - UV RESISTANCE LOCUS 8 (UVR8) is an ultraviolet-B (UVB) radiation photoreceptor
      that mediates light responses in plants. How plant UVR8 acts in response to UVB
      light is not well understood. Here, we report the identification and
      characterization of the Arabidopsis WRKY DNA-BINDING PROTEIN 36 (WRKY36) protein.
      WRKY36 interacts with UVR8 in yeast and Arabidopsis cells and it promotes
      hypocotyl elongation by inhibiting HY5 transcription. Inhibition of hypocotyl
      elongation under UVB requires the inhibition of WRKY36. WRKY36 binds to the W-box
      motif of the HY5 promoter to inhibit its transcription, while nuclear localized
      UVR8 directly interacts with WRKY36 to inhibit WRKY36-DNA binding both in vitro
      and in vivo, leading to the release of inhibition of HY5 transcription. These
      results indicate that WRKY36 is a negative regulator of HY5 and that UVB
      represses WRKY36 via UVR8 to promote the transcription of HY5 and
      photomorphogenesis. The UVR8-WRKY36 interaction in the nucleus represents a novel
      mechanism of early UVR8 signal transduction in Arabidopsis.

PMID- 29379155
TI  - A genome for gnetophytes and early evolution of seed plants.
AB  - Gnetophytes are an enigmatic gymnosperm lineage comprising three genera, Gnetum,
      Welwitschia and Ephedra, which are morphologically distinct from all other seed
      plants. Their distinctiveness has triggered much debate as to their origin,
      evolution and phylogenetic placement among seed plants. To increase our
      understanding of the evolution of gnetophytes, and their relation to other seed
      plants, we report here a high-quality draft genome sequence for Gnetum montanum,
      the first for any gnetophyte. By using a novel genome assembly strategy to deal
      with high levels of heterozygosity, we assembled >4 Gb of sequence encoding
      27,491 protein-coding genes. Comparative analysis of the G. montanum genome with
      other gymnosperm genomes unveiled some remarkable and distinctive genomic
      features, such as a diverse assemblage of retrotransposons with evidence for
      elevated frequencies of elimination rather than accumulation, considerable
      differences in intron architecture, including both length distribution and
      proportions of (retro) transposon elements, and distinctive patterns of
      proliferation of functional protein domains. Furthermore, a few gene families
      showed Gnetum-specific copy number expansions (for example, cellulose synthase)
      or contractions (for example, Late Embryogenesis Abundant protein), which could
      be connected with Gnetum's distinctive morphological innovations associated with
      their adaptation to warm, mesic environments. Overall, the G. montanum genome
      enables a better resolution of ancestral genomic features within seed plants, and
      the identification of genomic characters that distinguish Gnetum from other
      gymnosperms.

PMID- 29379157
TI  - Plant behaviour from human imprints and the cultivation of wild cereals in
      Holocene Sahara.
AB  - The human selection of food plants cannot always have been aimed exclusively at
      isolating the traits typical of domesticated species today. Each phase of global
      change must have obliged plants and humans to cope with and develop innovative
      adaptive strategies. Hundreds of thousands of wild cereal seeds from the Holocene
      'green Sahara' tell a story of cultural trajectories and environmental
      instability revealing that a complex suite of weediness traits were preferred by
      both hunter-gatherers and pastoralists. The archaeobotanical record of the
      Takarkori rockshelter in southwest Libya covering four millennia of human
      occupation in the central Sahara gives us a unique insight into long-term plant
      manipulation and cultivation without domestication. The success of a number of
      millets was rooted in their invasive-opportunistic behaviour, rewarded during
      their coexistence with people in Africa. These wild plants were selected for
      features that were precious in the past but pernicious for agriculture today.
      Reconnecting past practices with modern farming strategies can help us to seek
      out the best resources for the future.

PMID- 29379159
TI  - Precision therapeutics in the NICU: why are we missing the mark?

PMID- 29379158
TI  - Stress during pregnancy and gestational weight gain.
AB  - OBJECTIVE: To evaluate the association between prenatal stress and gestational
      weight gain (GWG). STUDY DESIGN: This was an analysis of women recruited between
      2013-2015 from four sites in the US. We tested associations between responses at
      32-35 weeks to the Life Experiences Survey (LES), a 37-item measure of events and
      perceived stress, and GWG categories. Bivariable comparisons and logistic
      regression were used to estimate the association between the total LES score and
      the odds of achieving adequate GWG. RESULT: Among the 725 women, those with
      adequate GWG had lower median LES scores (5) compared to women with inadequate
      (7) and excessive (7) GWG, p = 0.02. After adjusting for age, initial BMI,
      income, education, marital status and gestational diabetes, lower LES scores
      (multiples of the median) were associated with adequate GWG (aOR 0.81, 95% CI
      0.67-0.98). CONCLUSION: Lower reported stress, as measured by the LES, was
      associated with a greater chance of women achieving adequate GWG. This
      relationship highlights the potential for interventions directed toward
      psychosocial support to have salutary effects upon GWG.

PMID- 29379160
TI  - The impact of altitude on screening for critical congenital heart disease.
AB  - OBJECTIVES: The objectives were to determine the frequency with which pulse
      oximetry identifies critical congenital heart defects in asymptomatic full-term
      and late preterm newborns using the AAP expert panel algorithm in a variety of
      different hospital settings and to evaluate the impact of altitude on the rate of
      positive screens. METHODS: We conducted a prospective clinical study of
      implementation of a newborn pulse oximetry screening for congenital heart disease
      in 34 independent hospitals. Infants were eligible for enrollment if their
      gestational age was 35-44 weeks. RESULTS: Of the 34 sites which enrolled infants
      into our study, 24 were located at or below 2000 feet; 5 were located between
      4700 and 6000 feet and 5 were located above 6000 feet in altitude. We screened
      6109 infants; 65 (1.1%) had a positive screen. There were no differences in
      median gestational age, birth weight, mode of delivery or race/ethnicity for
      infants with a positive screen compared to infants with a negative screen.
      Infants with positive screens were more often male and more often born at sites
      located at high altitudes. The frequency of a positive screen increased from 0.2%
      for infants born at sites at or less than 2000 feet to 6% for sites located above
      6000 feet. We stopped enrollment at the site located at 8163 feet after enrolling
      65 infants because 23 (35%) were positive. CONCLUSIONS: Screening infants for
      critical cardiac defects at altitude is complicated by the increased false
      positive screens.

PMID- 29379161
TI  - The impact of first trimester fasting glucose level on adverse perinatal outcome.
AB  - OBJECTIVE: To evaluate the impact of first trimester fasting glucose (FTFG) level
      on perinatal outcome. STUDY DESIGN: A retrospective cohort study of singleton
      deliveries. Maternal and neonatal outcome were compared between two groups-women
      with FTFG < 95 mg/dl and FTFG >= 95 mg/dl. Women with pre-gestational diabetes
      were excluded. RESULTS: Five thousand and thirty women met inclusion criteria. Of
      whom, 4644 (92.3%) had FTFG < 95 mg/dl and 386 (7.7%) had FTFG >= 95 mg/dl. Women
      with FTFG >= 95 mg/dl had higher rates of gestational hypertension (2.33 vs.
      0.7%) and gestational diabetes (9.07 vs. 2.86%), p < 0.05 for both. Moreover,
      they had higher rates of cesarean delivery and arrest of descent, p < 0.05.
      Composite diabetes outcome was significantly higher among women with FTFG >= 95
      mg/dl (8 vs. 3%, p = 0.002). After adjusting for potential confounders, composite
      diabetes outcome (aOR = 1.942 95% CI 1.265-2.981, p = 0.002) and gestational
      hypertension (aOR = 2.827 95% CI 1.295-6.175, p = 0.009) remained significantly
      higher in the FTFG >= 95 mg/dl group. CONCLUSION: FTFG >= 95 mg/dl is an
      independent risk factor for adverse perinatal outcome including gestational
      hypertension and diabetes-related complications.

PMID- 29379162
TI  - PAX8 activates a p53-p21-dependent pro-proliferative effect in high grade serous
      ovarian carcinoma.
AB  - High grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer
      and it is now widely accepted that this disease often originates from the
      fallopian tube epithelium. PAX8 is a fallopian tube lineage marker with an
      essential role in embryonal female genital tract development. In the adult
      fallopian tube, PAX8 is expressed in the fallopian tube secretory epithelial cell
      (FTSEC) and its expression is maintained through the process of FTSEC
      transformation to HGSC. We now report that PAX8 has a pro-proliferative and anti
      apoptotic role in HGSC. The tumor suppressor gene TP53 is mutated in close to
      100% of HGSC; in the majority of cases, these are missense mutations that endow
      the mutant p53 protein with potential gain of function (GOF) oncogenic
      activities. We show that PAX8 positively regulates the expression of TP53 in HGSC
      and the pro-proliferative role of PAX8 is mediated by the GOF activity of mutant
      p53. Surprisingly, mutant p53 transcriptionally activates the expression of p21,
      which localizes to the cytoplasm of HGSC cells where it plays a non-canonical,
      pro-proliferative role. Together, our findings illustrate how TP53 mutations in
      HGSC subvert a normal regulatory pathway into a driver of tumor progression.

PMID- 29379163
TI  - c-Src activity is differentially required by cancer cell motility modes.
AB  - Cancer cell migration requires that cells respond and adapt to their
      surroundings. In the absence of extracellular matrix cues, cancer cells will
      undergo a mesenchymal to ameboid transition, whereas a highly confining space
      will trigger a switch to "leader bleb-based" migration. To identify oncogenic
      signaling pathways mediating these transitions, we undertook a targeted screen
      using clinically useful inhibitors. Elevated Src activity was found to change
      actin and focal adhesion dynamics, whereas inhibiting Src triggered focal
      adhesion disassembly and blebbing. On non-adherent substrates and in collagen
      matrices, amoeboid-like, blebbing cells having high Src activity formed
      protrusions of the plasma membrane. To evaluate the role of Src in confined
      cells, we use a novel approach that places cells under a slab of
      polydimethylsiloxane (PDMS), which is held at a defined height. Using this
      method, we find that leader bleb-based migration is resistant to Src inhibition.
      High Src activity was found to markedly change the architecture of cortical
      actomyosin, reduce cell mechanical properties, and the percentage of cells that
      undergo leader bleb-based migration. Thus, Src is a signal transducer that can
      potently influence transitions between migration modes with implications for the
      rational development of metastasis inhibitors.

PMID- 29379164
TI  - TRIM25 enhances cell growth and cell survival by modulating p53 signals via
      interaction with G3BP2 in prostate cancer.
AB  - Prostate cancer growth is promoted by the gene regulatory action of androgen
      receptor (AR) and its downstream signals. The aberrant dysfunction of tumor
      suppressor p53 has an important role in the prognosis of cancer. We previously
      found that androgen treatments translocate p53 to the cytoplasm. The mechanism of
      this translocation depends on sumoylation of p53 by complex of SUMO E3 ligase
      RanBP2 with androgen-induced GTPase-activating protein-binding protein 2 (G3BP2).
      Here, we identified tripartite motif-containing protein 25 (TRIM25)/estrogen
      responsive finger protein (Efp) as a novel interacting partner of G3BP2 protein
      complex. Then, we demonstrated that TRIM25 knockdown resulted in p53 downstream
      activation for cell cycle inhibition and apoptosis induction in LNCaP and 22Rv1
      cells. In contrast, overexpression of TRIM25 promoted prostate cancer cell
      proliferation and inhibited apoptosis by docetaxel treatment in LNCaP cells. We
      observed that p53 activity was reduced by mechanism of G3BP2-mediated nuclear
      export in TRIM25-overexpressing prostate cancer cells. We also found TRIM25 is
      important for G3BP2/RanBP2-mediated p53 modification. Clinically, we newly
      demonstrated that TRIM25 is a prognostic factor for prostate cancer patients.
      Expression of TRIM25 is significantly associated with cytoplasmic p53 expression
      and G3BP2. Moreover, TRIM25 knockdown results in reduced tumor growth and
      increased p53 activity in the mouse xenograft model of prostate cancer. Thus, our
      findings show that overexpression of TRIM25 promoted prostate cancer cell
      proliferation and cell survival by modulating p53 nuclear export mechanism with
      G3BP2 interaction.

PMID- 29379167
TI  - High-dose methylprednisolone for the treatment of sinusoidal obstruction syndrome
      in adults.

PMID- 29379166
TI  - Aggressive serous epithelial ovarian cancer is potentially propagated by
      EpCAM+CD45+ phenotype.
AB  - Epithelial ovarian carcinoma (EOC) patients often acquire resistance against
      common chemotherapeutic drugs like paclitaxel and cisplatin. The mechanism
      responsible for the same is ambiguous. We have identified a putative drug
      resistant tumour cell phenotype (EpCAM+CD45+) in the ascitic fluid of EOC
      patients, which appears to originate from the primary tumour. These cells
      represent the major tumour burden and are more drug resistant compared to EpCAM+
      tumour cells due to the over-expression of SIRT1, ABCA1 and BCL2 genes. We have
      found that the entire EpCAM+CD45+ population is highly invasive with signature
      mesenchymal gene expression and also consists of subpopulations of ovarian cancer
      stem cells (CD133+ and CD117+CD44+). Additionally, we demonstrate that the
      EpCAM+CD45+ tumour cells over-express major histocompatibility complex class I
      antigen, which enable them to evade the natural killer cell-mediated immune
      surveillance. Preliminary evidence obtained in OVCAR-5 cells suggests that
      exosomes, secreted by non-tumour cells of the ascitic fluid, play an important
      role in rendering drug resistance and invasive properties to the cancer cells.
      Identification of such aggressive tumour cells and deciphering their origin is
      important for designing better drug targets for EOC.

PMID- 29379165
TI  - MUC1-C activates polycomb repressive complexes and downregulates tumor suppressor
      genes in human cancer cells.
AB  - The PRC2 and PRC1 complexes are aberrantly expressed in human cancers and have
      been linked to decreases in patient survival. MUC1-C is an oncoprotein that is
      also overexpressed in diverse human cancers and is associated with a poor
      prognosis. Recent studies have supported a previously unreported function for
      MUC1-C in activating PRC2 and PRC1 in cancer cells. In the regulation of PRC2,
      MUC1-C (i) drives transcription of the EZH2 gene, (ii) binds directly to EZH2,
      and (iii) enhances occupancy of EZH2 on target gene promoters with an increase in
      H3K27 trimethylation. Regarding PRC1, which is recruited to PRC2 sites in the
      hierarchical model, MUC1-C induces BMI1 transcription, forms a complex with BMI1,
      and promotes H2A ubiquitylation. MUC1-C thereby contributes to the integration of
      PRC2 and PRC1-mediated repression of tumor suppressor genes, such as CDH1,
      CDKN2A, PTEN and BRCA1. Like PRC2 and PRC1, MUC1-C is associated with the
      epithelial-mesenchymal transition (EMT) program, cancer stem cell (CSC) state,
      and acquisition of anticancer drug resistance. In concert with these
      observations, targeting MUC1-C downregulates EZH2 and BMI1, inhibits EMT and the
      CSC state, and reverses drug resistance. These findings emphasize the
      significance of MUC1-C as a therapeutic target for inhibiting aberrant PRC
      function and reprogramming the epigenome in human cancers.

PMID- 29379169
TI  - Impact of MICA and NKG2D polymorphisms in HLA-fully matched related and unrelated
      hematopoietic stem cell transplantation.

PMID- 29379168
TI  - Use of Defibrotide to help prevent post-transplant endothelial injury in a
      genetically predisposed infant with metachromatic leukodystrophy undergoing
      hematopoietic stem cell gene therapy.

PMID- 29379170
TI  - Changes to work status and household income of long-term allogeneic blood and
      marrow transplant survivors in New South Wales, Australia.

PMID- 29379171
TI  - Effective treatment of steroid and therapy-refractory acute graft-versus-host
      disease with a novel mesenchymal stromal cell product (MSC-FFM).
AB  - The inability to generate mesenchymal stromal cells (MSCs) of consistent potency
      likely is responsible for inconsistent clinical outcomes of patients with aGvHD
      receiving MSC products. We developed a novel MSC manufacturing protocol
      characterized by high in vitro potency and near-identity of individual doses,
      referred to as "MSC-Frankfurt am Main (MSC-FFM)". Herein, we report outcomes of
      the 69 patients who have received MSC-FFM. These were 51 children and 18 adults
      with refractory aGvHD grade II (4%), III (36%) or IV (59%). Patients were
      refractory either to frontline therapy (steroids) (29%) or to steroids and 1-5
      additional lines of immunosuppressants (71%) were given infusions in four weekly
      intervals. The day 28 overall response rate was 83%; at the last follow-up, 61%
      and 25% of patients were in complete or partial remission. The median follow-up
      was 8.1 months. Six-month estimate for cumulative incidence of non-relapse
      mortality was 27% (range, 16-38); leukemia relapse mortality was 2% (range, 0-5).
      This was associated with a superior six-month overall survival (OS) probability
      rate of 71% (range, 61-83), compared to the outcome of patients not treated with
      MSC-FFM. This novel product was effective in children and adults, suggesting that
      MSC-FFM represents a promising therapy for steroid refractory aGvHD.

PMID- 29379172
TI  - Solution structure and elevator mechanism of the membrane electron transporter
      CcdA.
AB  - Membrane oxidoreductase CcdA plays a central role in supplying reducing
      equivalents from the bacterial cytoplasm to the envelope. It transports electrons
      across the membrane using a single pair of cysteines by a mechanism that has not
      yet been elucidated. Here we report an NMR structure of the Thermus thermophilus
      CcdA (TtCcdA) in an oxidized and outward-facing state. CcdA consists of two
      inverted structural repeats of three transmembrane helices (2 * 3-TM). We
      computationally modeled and experimentally validated an inward-facing state,
      which suggests that CcdA uses an elevator-type movement to shuttle the reactive
      cysteines across the membrane. CcdA belongs to the LysE superfamily, and thus its
      structure may be relevant to other LysE clan transporters. Structure comparisons
      of CcdA, semiSWEET, Pnu, and major facilitator superfamily (MFS) transporters
      provide insights into membrane transporter architecture and mechanism.

PMID- 29379173
TI  - Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct
      nucleosomes.
AB  - Epigenetic regulation is mediated by protein complexes that couple recognition of
      chromatin marks to activity or recruitment of chromatin-modifying enzymes.
      Polycomb repressive complex 2 (PRC2), a gene silencer that methylates lysine 27
      of histone H3, is stimulated upon recognition of its own catalytic product and
      has been shown to be more active on dinucleosomes than H3 tails or single
      nucleosomes. These properties probably facilitate local H3K27me2/3 spreading,
      causing heterochromatin formation and gene repression. Here, cryo-EM
      reconstructions of human PRC2 bound to bifunctional dinucleosomes show how a
      single PRC2, via interactions with nucleosomal DNA, positions the H3 tails of the
      activating and substrate nucleosome to interact with the EED subunit and the SET
      domain of EZH2, respectively. We show how the geometry of the PRC2-DNA
      interactions allows PRC2 to accommodate varying lengths of the linker DNA between
      nucleosomes. Our structures illustrate how an epigenetic regulator engages with a
      complex chromatin substrate.

PMID- 29379174
TI  - Structural basis for recognition of diverse antidepressants by the human
      serotonin transporter.
AB  - Selective serotonin reuptake inhibitors are clinically prescribed antidepressants
      that act by increasing the local concentrations of neurotransmitters at synapses
      and in extracellular spaces via blockade of the serotonin transporter. Here we
      report X-ray structures of engineered thermostable variants of the human
      serotonin transporter bound to the antidepressants sertraline, fluvoxamine, and
      paroxetine. The drugs prevent serotonin binding by occupying the central
      substrate-binding site and stabilizing the transporter in an outward-open
      conformation. These structures explain how residues within the central site
      orchestrate binding of chemically diverse inhibitors and mediate transporter drug
      selectivity.

PMID- 29379176
TI  - Inorganic carbon addition stimulates snow algae primary productivity.
AB  - Earth has experienced glacial/interglacial oscillations accompanied by changes in
      atmospheric CO2 throughout much of its history. Today over 15 million square
      kilometers of Earth's land surface is covered in ice including glaciers, ice
      caps, and ice sheets. Glaciers are teeming with life and supraglacial snow and
      ice surfaces are often darkened by the presence of photoautotrophic snow algae,
      resulting in accelerated melt due to lowered albedo. Few studies report the
      productivity of snow algal communities and the parameters which constrain their
      growth on supraglacial surfaces-key factors for quantifying biologically induced
      albedo effects (bio-albedo). We demonstrate that snow algae primary productivity
      is stimulated by the addition of inorganic carbon. Our results indicate a
      positive feedback between increasing CO2 and snow algal primary productivity,
      underscoring the need for robust climate models of past and present
      glacial/interglacial oscillations to include feedbacks between supraglacial
      primary productivity, albedo, and atmospheric CO2.

PMID- 29379175
TI  - The ring-shaped hexameric helicases that function at DNA replication forks.
AB  - DNA replication requires separation of genomic duplex DNA strands, an operation
      that is performed by a hexameric ring-shaped helicase in all domains of life. The
      structures and chemomechanical actions of these fascinating machines are coming
      into sharper focus. Although there is no evolutionary relationship between the
      hexameric helicases of bacteria and those of archaea and eukaryotes, they share
      many fundamental features. Here we review recent studies of these two groups of
      hexameric helicases and the unexpected distinctions they have also unveiled.

PMID- 29379177
TI  - Climate change promotes parasitism in a coral symbiosis.
AB  - Coastal oceans are increasingly eutrophic, warm and acidic through the addition
      of anthropogenic nitrogen and carbon, respectively. Among the most sensitive taxa
      to these changes are scleractinian corals, which engineer the most biodiverse
      ecosystems on Earth. Corals' sensitivity is a consequence of their evolutionary
      investment in symbiosis with the dinoflagellate alga, Symbiodinium. Together, the
      coral holobiont has dominated oligotrophic tropical marine habitats. However,
      warming destabilizes this association and reduces coral fitness. It has been
      theorized that, when reefs become warm and eutrophic, mutualistic Symbiodinium
      sequester more resources for their own growth, thus parasitizing their hosts of
      nutrition. Here, we tested the hypothesis that sub-bleaching temperature and
      excess nitrogen promotes symbiont parasitism by measuring respiration (costs) and
      the assimilation and translocation of both carbon (energy) and nitrogen (growth;
      both benefits) within Orbicella faveolata hosting one of two Symbiodinium
      phylotypes using a dual stable isotope tracer incubation at ambient (26  degrees
      C) and sub-bleaching (31  degrees C) temperatures under elevated nitrate. Warming
      to 31  degrees C reduced holobiont net primary productivity (NPP) by 60% due to
      increased respiration which decreased host %carbon by 15% with no apparent cost
      to the symbiont. Concurrently, Symbiodinium carbon and nitrogen assimilation
      increased by 14 and 32%, respectively while increasing their mitotic index by
      15%, whereas hosts did not gain a proportional increase in translocated
      photosynthates. We conclude that the disparity in benefits and costs to both
      partners is evidence of symbiont parasitism in the coral symbiosis and has major
      implications for the resilience of coral reefs under threat of global change.

PMID- 29379178
TI  - Deposition rates of viruses and bacteria above the atmospheric boundary layer.
AB  - Aerosolization of soil-dust and organic aggregates in sea spray facilitates the
      long-range transport of bacteria, and likely viruses across the free atmosphere.
      Although long-distance transport occurs, there are many uncertainties associated
      with their deposition rates. Here, we demonstrate that even in pristine
      environments, above the atmospheric boundary layer, the downward flux of viruses
      ranged from 0.26 * 109 to >7 * 109 m-2 per day. These deposition rates were 9-461
      times greater than the rates for bacteria, which ranged from 0.3 * 107 to >8 *
      107 m-2 per day. The highest relative deposition rates for viruses were
      associated with atmospheric transport from marine rather than terrestrial
      sources. Deposition rates of bacteria were significantly higher during rain
      events and Saharan dust intrusions, whereas, rainfall did not significantly
      influence virus deposition. Virus deposition rates were positively correlated
      with organic aerosols <0.7 MUm, whereas, bacteria were primarily associated with
      organic aerosols >0.7 MUm, implying that viruses could have longer residence
      times in the atmosphere and, consequently, will be dispersed further. These
      results provide an explanation for enigmatic observations that viruses with very
      high genetic identity can be found in very distant and different environments.

PMID- 29379179
TI  - Energy limitation of cyanophage development: implications for marine carbon
      cycling.
AB  - Marine cyanobacteria are responsible for ~25% of the fixed carbon that enters the
      ocean biosphere. It is thought that abundant co-occurring viruses play an
      important role in regulating population dynamics of cyanobacteria and thus the
      cycling of carbon in the oceans. Despite this, little is known about how viral
      infections 'play-out' in the environment, particularly whether infections are
      resource or energy limited. Photoautotrophic organisms represent an ideal model
      to test this since available energy is modulated by the incoming light intensity
      through photophosphorylation. Therefore, we exploited phototrophy of the
      environmentally relevant marine cyanobacterium Synechococcus and monitored growth
      of a cyanobacterial virus (cyanophage). We found that light intensity has a
      marked effect on cyanophage infection dynamics, but that this is not manifest by
      a change in DNA synthesis. Instead, cyanophage development appears energy limited
      for the synthesis of proteins required during late infection. We posit that
      acquisition of auxiliary metabolic genes (AMGs) involved in light-dependent
      photosynthetic reactions acts to overcome this limitation. We show that
      cyanophages actively modulate expression of these AMGs in response to light
      intensity and provide evidence that such regulation may be facilitated by a novel
      mechanism involving light-dependent splicing of a group I intron in a
      photosynthetic AMG. Altogether, our data offers a mechanistic link between
      diurnal changes in irradiance and observed community level responses in
      metabolism, i.e., through an irradiance-dependent, viral-induced release of
      dissolved organic matter (DOM).

PMID- 29379180
TI  - Exploration of the role of the virulence factor ElrA during Enterococcus faecalis
      cell infection.
AB  - Enterococcus faecalis, an organism generally not pathogenic for healthy humans,
      has the potential to cause disease in susceptible hosts. While it seems to be
      equipped to interact with and circumvent host immune defense, most of the
      molecular and cellular mechanisms underlying the enterococcal infectious process
      remain elusive. Here, we investigated the role of the Enterococcal Leucine Rich
      protein A (ElrA), an internalin-like protein of E. faecalis also known as a
      virulence factor. ElrA was previously shown to prevent adhesion to macrophages.
      We show that ElrA does not inhibit the basic phagocytic process, but is able to
      prevent sensing and migration of macrophages toward E. faecalis. Presence or
      absence of FHL2, a eukaryotic partner of ElrA, does not affect the ElrA-dependent
      mechanism preventing macrophage migration. However, we highlight a partial
      contribution of FHL2 in ElrA-mediated virulence in vivo. Our results indicate
      that ElrA plays at least a dual role of which anti-phagocytic activity may
      contribute to dissemination of extracellular E. faecalis during infection.

PMID- 29379182
TI  - History and environment shape species pools and community diversity in European
      beech forests.
AB  - A central hypothesis of ecology states that regional diversity influences local
      diversity through species-pool effects. Species pools are supposedly shaped by
      large-scale factors and then filtered into ecological communities, but
      understanding these processes requires the analysis of large datasets across
      several regions. Here, we use a framework of community assembly at a continental
      scale to test the relative influence of historical and environmental drivers, in
      combination with regional or local species pools, on community species richness
      and community completeness. Using 42,173 vegetation plots sampled across European
      beech forests, we found that large-scale factors largely accounted for species
      pool sizes. At the regional scale, main predictors reflected historical
      contingencies related to post-glacial dispersal routes, whereas at the local
      scale, the influence of environmental filters was predominant. Proximity to
      Quaternary refugia and high precipitation were the main factors supporting
      community species richness, especially among beech forest specialist plants.
      Models for community completeness indicate the influence of large-scale factors,
      further suggesting community saturation as a result of dispersal limitation or
      biotic interactions. Our results empirically demonstrate how historical factors
      complement environmental gradients to provide a better understanding of
      biodiversity patterns across multiple regions.

PMID- 29379181
TI  - Formulation, evaluation and bioactive potential of Xylaria primorskensis
      terpenoid nanoparticles from its major compound xylaranic acid.
AB  - In recent years, fungi have been shown to produce a plethora of new bioactive
      secondary metabolites of interest, as new lead structures for medicinal and other
      pharmacological applications. The present investigation was carried out to study
      the pharmacological properties of a potent and major bioactive compound:
      xylaranic acid, which was obtained from Xylaria primorskensis (X. primorskensis)
      terpenoids in terms of antibacterial activity, antioxidant potential against DPPH
      & H2O2 radicals and anticancer activity against human lung cancer cells. Due to
      terpenoid nature, low water solubility and wretched bioavailability, its
      pharmacological use is limited. To overcome these drawbacks, a novel xylaranic
      acid silver nanoparticle system (AgNPs) is developed. In addition to improving
      its solubility and bioavailability, other advantageous pharmacological properties
      has been evaluated. Furthermore, enhanced anticancer activity of xylaranic acid
      and its AgNPs due to induced apoptosis were also confirmed by determining the
      expression levels of apoptosis regulatory genes p53, bcl-2 and caspase-3 via qRT
      PCR method. This is the first study developing the novel xylaranic acid silver
      nanoparticle system and enlightening its therapeutic significance with its
      improved physico-chemical properties and augmented bioactive potential.

PMID- 29379183
TI  - New Egyptian sauropod reveals Late Cretaceous dinosaur dispersal between Europe
      and Africa.
AB  - Prominent hypotheses advanced over the past two decades have sought to
      characterize the Late Cretaceous continental vertebrate palaeobiogeography of
      Gondwanan landmasses, but have proved difficult to test because terrestrial
      vertebrates from the final ~30 million years of the Mesozoic are extremely rare
      and fragmentary on continental Africa (including the then-conjoined Arabian
      Peninsula but excluding the island of Madagascar). Here we describe a new
      titanosaurian sauropod dinosaur, Mansourasaurus shahinae gen. et sp. nov., from
      the Upper Cretaceous (Campanian) Quseir Formation of the Dakhla Oasis of the
      Egyptian Western Desert. Represented by an associated partial skeleton that
      includes cranial elements, Mansourasaurus is the most completely preserved land
      living vertebrate from the post-Cenomanian Cretaceous (~94-66 million years ago)
      of the African continent. Phylogenetic analyses demonstrate that Mansourasaurus
      is nested within a clade of penecontemporaneous titanosaurians from southern
      Europe and eastern Asia, thereby providing the first unambiguous evidence for a
      post-Cenomanian Cretaceous continental vertebrate clade that inhabited both
      Africa and Europe. The close relationship of Mansourasaurus to coeval Eurasian
      titanosaurians indicates that terrestrial vertebrate dispersal occurred between
      Eurasia and northern Africa after the tectonic separation of the latter from
      South America ~100 million years ago. These findings counter hypotheses that
      dinosaur faunas of the African mainland were completely isolated during the post
      Cenomanian Cretaceous.

PMID- 29379184
TI  - Fossils, phylogenies and the evolving climate niche.

PMID- 29379185
TI  - The impact of endothermy on the climatic niche evolution and the distribution of
      vertebrate diversity.
AB  - Understanding the mechanisms by which the abiotic and biotic requirements of
      species, or ecological niches, change over time is a central issue in
      evolutionary biology. Niche evolution is poorly understood at both the
      macroecological and macroevolutionary scales, as niches can shift over short
      periods of time but appear to change more slowly over longer timescales. Although
      reconstructing past niches has always been a major concern for palaeontologists
      and evolutionary biologists, only a few recent studies have successfully
      determined the factors that affect niche evolution. Here, we compare the
      evolution of climatic niches in four main groups of terrestrial vertebrates using
      a modelling approach integrating both palaeontological and neontological data,
      and large-scale datasets that contain information on the current distributions,
      phylogenetic relationships and fossil records for a total of 11,465 species. By
      reconstructing historical shifts in geographical ranges and climatic niches, we
      show that niche shifts are significantly faster in endotherms (birds and mammals)
      than in ectotherms (squamates and amphibians). We further demonstrate that the
      diversity patterns of the four clades are directly affected by the rate of niche
      evolution, with fewer latitudinal shifts in ectotherms.

PMID- 29379186
TI  - Redundant regulation.

PMID- 29379188
TI  - Innate immunity: Sensing bacterial messages.

PMID- 29379189
TI  - Cancer immunotherapy in 2017: The breakthrough of the microbiota.

PMID- 29379187
TI  - Dynamic evolution of regulatory element ensembles in primate CD4+ T cells.
AB  - How evolutionary changes at enhancers affect the transcription of target genes
      remains an important open question. Previous comparative studies of gene
      expression have largely measured the abundance of messenger RNA, which is
      affected by post-transcriptional regulatory processes, hence limiting inferences
      about the mechanisms underlying expression differences. Here, we directly
      measured nascent transcription in primate species, allowing us to separate
      transcription from post-transcriptional regulation. We used precision run-on and
      sequencing to map RNA polymerases in resting and activated CD4+ T cells in
      multiple human, chimpanzee and rhesus macaque individuals, with rodents as
      outgroups. We observed general conservation in coding and non-coding
      transcription, punctuated by numerous differences between species, particularly
      at distal enhancers and non-coding RNAs. Genes regulated by larger numbers of
      enhancers are more frequently transcribed at evolutionarily stable levels,
      despite reduced conservation at individual enhancers. Adaptive nucleotide
      substitutions are associated with lineage-specific transcription and at one
      locus, SGPP2, we predict and experimentally validate that multiple substitutions
      contribute to human-specific transcription. Collectively, our findings suggest a
      pervasive role for evolutionary compensation across ensembles of enhancers that
      jointly regulate target genes.

PMID- 29379190
TI  - Tumour immunology: Natural killer cells spy greedy tumours.

PMID- 29379191
TI  - Genetic cluster of fragile X syndrome in a Colombian district.
AB  - BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited
      intellectual disabilities and autism. The reported prevalence of the full
      mutation (FM) gene FMR1 in the general population is 0.2-0.4 per 1000 males and
      0.125-0.4 per 1000 females. Population screening for FMR1 expanded alleles has
      been performed in newborns and in an adult population. However, it has never been
      carried out in an entire town. Ricaurte is a Colombian district with 1186
      habitants, with a high prevalence of FXS, which was first described by
      cytogenetic techniques in 1999. METHODS: Using a PCR-based approach, screening
      for FXS was performed on blood spot samples obtained from 926 (502 males and 424
      females) inhabitants from Ricaurte, accounting for 78% of total population.
      RESULTS: A high prevalence of carriers of the expanded allele was observed in all
      FXS mutation categories. Using the Bayesian methods the carrier frequency of FM
      was 48.2 (95% Credibility Region CR: 36.3-61.5) per 1000 males and 20.5 (95%
      CR:13.5-28.6) per 1000 females; the frequency of premutation carrier was 14.1
      (95% RC: 8.0-21.7) per 1000 males (95% RC: 8.0-21.7 per 1000 males) and 35.9 (95%
      RC: 26.5-46.2) per 1000 for females (95% RC: 26.5-46.2 per 1000 females), and
      gray zone carrier was 13.4 (95% RC: 7.4-20.7) per 1000 males (95% RC: 7.4-20.7
      per 1000 males) and 42.2 (95% RC: 32.2-53.8) per 1000 for females (95% RC: 32.2
      53.8 per 1000 females). Differences in carrier frequencies were observed for
      premutation and FM alleles between natives and non-natives. CONCLUSIONS: This
      study shows that in Ricaurte the carrier frequencies of FMR1 expanded alleles
      (premutations and FMs) are higher than those reported in the literature,
      suggesting that Ricaurte constitutes a genetic cluster of FXS.

PMID- 29379192
TI  - Genetic variation in populations from central Argentina based on mitochondrial
      and Y chromosome DNA evidence.
AB  - We present new data and analysis on the genetic variation of contemporary
      inhabitants of central Argentina, including a total of 812 unrelated individuals
      from 20 populations. Our goal was to bring new elements for understanding micro
      evolutionary and historical processes that generated the genetic diversity of the
      region, using molecular markers of uniparental inheritance (mitochondrial DNA and
      Y chromosome). Almost 76% of the individuals show mitochondrial lineages of
      American origin. The Native American haplogroups predominate in all surveyed
      localities, except in one. The larger presence of Eurasian maternal lineages were
      observed in the plains (Pampas) of the southeast, whereas the African lineages
      are more frequent in northern Cordoba. On the other hand, the analysis of 258
      male samples reveals that 92% of them present Eurasian paternal lineages, 7%
      carry Native American haplogroups, and only 1% of the males show African
      lineages. The maternal lineages have high genetic diversity homogeneously
      distributed throughout central Argentina, probably as result of a recent common
      origin and sustained gene flow. Migratory events that occurred in colonial and
      recent times should have contributed to hiding any traces of differentiation that
      might have existed in the past. The analysis of paternal lineages showed also
      homogeneous distribution of the variation together with a drastic reduction of
      the native male population.

PMID- 29379193
TI  - The inclusion of genomic data in the 2015 revision of Japan's Protection of
      Personal Information Act: protection of wider range of genomic data as our next
      challenge.

PMID- 29379194
TI  - Psychosocial impact on mothers receiving expanded newborn screening results.
AB  - Expanded newborn screening (NBS) for genetic disorders has improved diagnosis of
      numerous treatable diseases, positively impacting children's health outcomes.
      However, research about the psychological impact of expanded NBS on families,
      especially mothers, has been mixed. Our study examined associations between
      maternal experiences of expanded NBS and subsequent psychosocial functioning and
      parenting stress in mothers whose infants received either true negative (TN),
      true positive (TP) or false positive (FP) results after a 4- to 6-month period.
      The Parenting Stress Index and the Depression, Anxiety and Stress Scale were used
      to assess symptoms of anxiety, stress and depression in 3 sets of mothers, whose
      infants received TN (n = 31), TP (n = 8) or FP (n = 18) results. Multivariate
      analyses of variance (MANOVA) results revealed no significant differences among
      these three groups of mothers regarding overall anxiety, stress and depression.
      However, FP mothers experienced lower levels of stress related to their own
      health compared to TN group. Two potential trends were also identified; results
      suggested TN mothers might experience higher levels of isolation than mothers in
      the TP group and that FP mothers might report higher stress levels in relation to
      spousal relationships compared to the TN group. FP mothers seemed to report
      similar or better levels of psychosocial functioning than TN mothers. Our
      findings are encouraging with respect to impacts of NBS on maternal well-being.
      We also identify key areas for improvement (parental education) and research
      (isolation and spousal relationships).

PMID- 29379195
TI  - Knowledge, experiences and attitudes concerning genetics among retinoblastoma
      survivors and parents.
AB  - Clinical genetic services are increasingly providing a more nuanced understanding
      of genetic disease diagnostics and future risk for patients. Effectively
      conveying genetic information is essential for patients to make informed
      decisions. This is especially important for survivors of heritable cancers such
      as retinoblastoma (childhood eye cancer), where survivors who carry a germline
      mutation in the RB1 gene are at increased risk of second cancers in adulthood,
      and of passing on the disease risk to future offspring. We conducted focus groups
      with adult survivors of retinoblastoma and parents of children with
      retinoblastoma, to uncover their knowledge of, experiences with and attitudes
      about retinoblastoma genetics and related impacts of the cancer. Results revealed
      that participants understood that retinoblastoma was a genetic disease, but often
      misunderstood the implications of genetics on cancer phenotype and risk.
      Experiences with genetic testing and counseling were generally positive, however,
      participants reported challenges in accessing genetic information and
      psychosocial support. Participants suggested more educational resources, peer-to
      peer counseling, and psychosocial support would enhance uptake of important
      genetic information. The results of the study will inform patient-oriented
      approaches to deliver comprehensive genetic healthcare.

PMID- 29379197
TI  - BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like
      syndrome.
AB  - We found that the clinical phenotype associated with BRD4 haploinsufficiency
      overlapped with that of Cornelia de Lange syndrome (CdLS), which is most often
      caused by mutation of NIPBL. More typical CdLS was observed with a de novo BRD4
      missense variant, which retained the ability to coimmunoprecipitate with NIPBL,
      but bound poorly to acetylated histones. BRD4 and NIPBL displayed correlated
      binding at super-enhancers and appeared to co-regulate developmental gene
      expression.

PMID- 29379196
TI  - Genome-wide association study of Hirschsprung disease detects a novel low
      frequency variant at the RET locus.
AB  - Hirschsprung disease (HSCR) is a congenital disorder with a population incidence
      of ~1/5000 live births, defined by an absence of enteric ganglia along variable
      lengths of the colon. HSCR genome-wide association studies (GWAS) have found
      common associated variants at RET, SEMA3, and NRG1, but they still fail to
      explain all of its heritability. To enhance gene discovery, we performed a GWAS
      of 170 cases identified from the Danish nationwide pathology registry with 4717
      controls, based on 6.2 million variants imputed from the haplotype reference
      consortium panel. We found a novel low-frequency variant (rs144432435), which,
      when conditioning on the lead RET single-nucleotide polymorphism (SNP), was of
      genome-wide significance in the discovery analysis. This conditional association
      signal was replicated in a Swedish HSCR cohort with discovery plus replication
      meta-analysis conditional odds ratio of 6.6 (P = 7.7 * 10-10; 322 cases and 4893
      controls). The conditional signal was, however, not replicated in two HSCR
      cohorts from USA and Finland, leading to the hypothesis that rs144432435 tags a
      rare haplotype present in Denmark and Sweden. Using the genome-wide complex trait
      analysis method, we estimated the SNP heritability of HSCR to be 88%, close to
      estimates based on classical family studies. Moreover, by using Lasso (least
      absolute shrinkage and selection operator) regression we were able to construct a
      genetic HSCR predictor with a area under the receiver operator characteristics
      curve of 76% in an independent validation set. In conclusion, we combined the
      largest collection of sporadic Hirschsprung cases to date (586 cases) to further
      elucidate HSCR's genetic architecture.

PMID- 29379198
TI  - Exome-wide analyses identify low-frequency variant in CYP26B1 and additional
      coding variants associated with esophageal squamous cell carcinoma.
AB  - Genome-wide association studies have identified common variants associated with
      risk of esophageal squamous cell carcinoma (ESCC). However, these common variants
      cannot explain all heritability of ESCC. Here we report an exome-wide
      interrogation of 3,714 individuals with ESCC and 3,880 controls for low-frequency
      susceptibility loci, with two independent replication samples comprising 7,002
      cases and 8,757 controls. We found six new susceptibility loci in CCHCR1, TCN2,
      TNXB, LTA, CYP26B1 and FASN (P = 7.77 * 10-24 to P = 1.49 * 10-11), and three low
      frequency variants had relatively high effect size (odds ratio > 1.5).
      Individuals with the rs138478634-GA genotype had significantly lower levels of
      serum all-trans retinoic acid, an anticancer nutrient, than those with the
      rs138478634-GG genotype (P = 0.0004), most likely due to an enhanced capacity of
      variant CYP26B1 to catabolize this agent. These findings emphasize the important
      role of rare coding variants in the development of ESCC.

PMID- 29379199
TI  - Enhancer invasion shapes MYCN-dependent transcriptional amplification in
      neuroblastoma.
AB  - Amplification of the locus encoding the oncogenic transcription factor MYCN is a
      defining feature of high-risk neuroblastoma. Here we present the first dynamic
      chromatin and transcriptional landscape of MYCN perturbation in neuroblastoma. At
      oncogenic levels, MYCN associates with E-box binding motifs in an affinity
      dependent manner, binding to strong canonical E-boxes at promoters and invading
      abundant weaker non-canonical E-boxes clustered at enhancers. Loss of MYCN leads
      to a global reduction in transcription, which is most pronounced at MYCN target
      genes with the greatest enhancer occupancy. These highly occupied MYCN target
      genes show tissue-specific expression and are linked to poor patient survival.
      The activity of genes with MYCN-occupied enhancers is dependent on the tissue
      specific transcription factor TWIST1, which co-occupies enhancers with MYCN and
      is required for MYCN-dependent proliferation. These data implicate tissue
      specific enhancers in defining often highly tumor-specific 'MYC target gene
      signatures' and identify disruption of the MYCN enhancer regulatory axis as a
      promising therapeutic strategy in neuroblastoma.

PMID- 29379200
TI  - Shared genetic effects on chromatin and gene expression indicate a role for
      enhancer priming in immune response.
AB  - Regulatory variants are often context specific, modulating gene expression in a
      subset of possible cellular states. Although these genetic effects can play
      important roles in disease, the molecular mechanisms underlying context
      specificity are poorly understood. Here, we identified shared quantitative trait
      loci (QTLs) for chromatin accessibility and gene expression in human macrophages
      exposed to IFNgamma, Salmonella and IFNgamma plus Salmonella. We observed that
      ~60% of stimulus-specific expression QTLs with a detectable effect on chromatin
      altered the chromatin accessibility in naive cells, thus suggesting that they
      perturb enhancer priming. Such variants probably influence binding of cell-type
      specific transcription factors, such as PU.1, which can then indirectly alter the
      binding of stimulus-specific transcription factors, such as NF-kappaB or STAT2.
      Thus, although chromatin accessibility assays are powerful for fine-mapping
      causal regulatory variants, detecting their downstream effects on gene expression
      will be challenging, requiring profiling of large numbers of stimulated cellular
      states and time points.

PMID- 29379202
TI  - Imaging the rainbow.

PMID- 29379201
TI  - Morphable 3D mesostructures and microelectronic devices by multistable buckling
      mechanics.
AB  - Three-dimensional (3D) structures capable of reversible transformations in their
      geometrical layouts have important applications across a broad range of areas.
      Most morphable 3D systems rely on concepts inspired by origami/kirigami or
      techniques of 3D printing with responsive materials. The development of schemes
      that can simultaneously apply across a wide range of size scales and with classes
      of advanced materials found in state-of-the-art microsystem technologies remains
      challenging. Here, we introduce a set of concepts for morphable 3D mesostructures
      in diverse materials and fully formed planar devices spanning length scales from
      micrometres to millimetres. The approaches rely on elastomer platforms deformed
      in different time sequences to elastically alter the 3D geometries of supported
      mesostructures via nonlinear mechanical buckling. Over 20 examples have been
      experimentally and theoretically investigated, including mesostructures that can
      be reshaped between different geometries as well as those that can morph into
      three or more distinct states. An adaptive radiofrequency circuit and a
      concealable electromagnetic device provide examples of functionally
      reconfigurable microelectronic devices.

PMID- 29379203
TI  - Electrical detection of single magnetic skyrmions in metallic multilayers at room
      temperature.
AB  - Magnetic skyrmions are topologically protected whirling spin textures that can be
      stabilized in magnetic materials by an asymmetric exchange interaction between
      neighbouring spins that imposes a fixed chirality. Their small size, together
      with the robustness against external perturbations, make magnetic skyrmions
      potential storage bits in a novel generation of memory and logic devices. To this
      aim, their contribution to the electrical transport properties of a device must
      be characterized-however, the existing demonstrations are limited to low
      temperatures and mainly in magnetic materials with a B20 crystal structure. Here
      we combine concomitant magnetic force microscopy and Hall resistivity
      measurements to demonstrate the electrical detection of sub-100 nm skyrmions in a
      multilayered thin film at room temperature. Furthermore, we detect and analyse
      the Hall signal of a single skyrmion, which indicates that it arises from the
      anomalous Hall effect with a negligible contribution from the topological Hall
      effect.

PMID- 29379204
TI  - A broadband achromatic metalens in the visible.
AB  - Metalenses consist of an array of optical nanoantennas on a surface capable of
      manipulating the properties of an incoming light wavefront. Various flat optical
      components, such as polarizers, optical imaging encoders, tunable phase
      modulators and a retroreflector, have been demonstrated using a metalens design.
      An open issue, especially problematic for colour imaging and display
      applications, is the correction of chromatic aberration, an intrinsic effect
      originating from the specific resonance and limited working bandwidth of each
      nanoantenna. As a result, no metalens has demonstrated full-colour imaging in the
      visible wavelength. Here, we show a design and fabrication that consists of GaN
      based integrated-resonant unit elements to achieve an achromatic metalens
      operating in the entire visible region in transmission mode. The focal length of
      our metalenses remains unchanged as the incident wavelength is varied from 400 to
      660 nm, demonstrating complete elimination of chromatic aberration at about 49%
      bandwidth of the central working wavelength. The average efficiency of a metalens
      with a numerical aperture of 0.106 is about 40% over the whole visible spectrum.
      We also show some examples of full-colour imaging based on this design.

PMID- 29379205
TI  - A modular platform for targeted RNAi therapeutics.
AB  - Previous studies have identified relevant genes and signalling pathways that are
      hampered in human disorders as potential candidates for therapeutics. Developing
      nucleic acid-based tools to manipulate gene expression, such as short interfering
      RNAs1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although
      major progress has been made in developing siRNA targeted delivery carriers,
      mainly by utilizing monoclonal antibodies (mAbs) for targeting4-8, their clinical
      translation has not occurred. This is in part because of the massive development
      and production requirements and the high batch-to-batch variability of current
      technologies, which rely on chemical conjugation. Here we present a self
      assembled modular platform that enables the construction of a theoretically
      unlimited repertoire of siRNA targeted carriers. The self-assembly of the
      platform is based on a membrane-anchored lipoprotein that is incorporated into
      siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable
      fragment (Fc) domain. We show that a simple switch of eight different mAbs
      redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The
      therapeutic potential of the platform is demonstrated in an inflammatory bowel
      disease model by targeting colon macrophages to reduce inflammatory symptoms, and
      in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce
      cell death and improve survival. This modular delivery platform represents a
      milestone in the development of precision medicine.

PMID- 29379206
TI  - Publisher Correction: An adaptive supramolecular hydrogel comprising self-sorting
      double nanofibre networks.
AB  - In the version of this Article originally published online, in Fig. 4b, in the
      lower-right image, the value of r was incorrect; it should have read 'r = 0.72'.
      This has now been corrected in all versions of the Article.

PMID- 29379207
TI  - Structural basis for neutralization of Japanese encephalitis virus by two potent
      therapeutic antibodies.
AB  - Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever
      and West Nile viruses, remains neglected and not well characterized 1 . JEV is
      the leading causative agent of encephalitis, and is responsible for thousands of
      deaths each year in Asia. Humoral immunity is essential for protecting against
      flavivirus infections and passive immunization has been demonstrated to be
      effective in curing disease2,3. Here, we demonstrate that JEV-specific monoclonal
      antibodies, 2F2 and 2H4, block attachment of the virus to its receptor and also
      prevent fusion of the virus. Neutralization of JEV by these antibodies is
      exceptionally potent and confers clear therapeutic benefit in mouse models. A
      single 20 MUg dose of these antibodies resulted in 100% survival and complete
      clearance of JEV from the brains of mice. The 4.7 A and 4.6 A resolution cryo
      electron microscopy structures of JEV-2F2-Fab and JEV-2H4-Fab complexes, together
      with the crystal structure of 2H4 Fab and our recent near-atomic structure of JEV
      4 , unveil the nature and location of epitopes targeted by the antibodies. Both
      2F2 and 2H4 Fabs bind quaternary epitopes that span across three adjacent
      envelope proteins. Our results provide a structural and molecular basis for the
      application of 2F2 and 2H4 to treat JEV infection.

PMID- 29379208
TI  - Differential depth distribution of microbial function and putative symbionts
      through sediment-hosted aquifers in the deep terrestrial subsurface.
AB  - An enormous diversity of previously unknown bacteria and archaea has been
      discovered recently, yet their functional capacities and distributions in the
      terrestrial subsurface remain uncertain. Here, we continually sampled a CO2
      driven geyser (Colorado Plateau, Utah, USA) over its 5-day eruption cycle to test
      the hypothesis that stratified, sandstone-hosted aquifers sampled over three
      phases of the eruption cycle have microbial communities that differ both in
      membership and function. Genome-resolved metagenomics, single-cell genomics and
      geochemical analyses confirmed this hypothesis and linked microorganisms to
      groundwater compositions from different depths. Autotrophic Candidatus
      "Altiarchaeum sp." and phylogenetically deep-branching nanoarchaea dominate the
      deepest groundwater. A nanoarchaeon with limited metabolic capacity is inferred
      to be a potential symbiont of the Ca. "Altiarchaeum". Candidate Phyla Radiation
      bacteria are also present in the deepest groundwater and they are relatively
      abundant in water from intermediate depths. During the recovery phase of the
      geyser, microaerophilic Fe- and S-oxidizers have high in situ genome replication
      rates. Autotrophic Sulfurimonas sustained by aerobic sulfide oxidation and with
      the capacity for N2 fixation dominate the shallow aquifer. Overall, 104 different
      phylum-level lineages are present in water from these subsurface environments,
      with uncultivated archaea and bacteria partitioned to the deeper subsurface.

PMID- 29379209
TI  - Spontaneous CRISPR loci generation in vivo by non-canonical spacer integration.
AB  - The adaptation phase of CRISPR-Cas immunity depends on the precise integration of
      short segments of foreign DNA (spacers) into a specific genomic location within
      the CRISPR locus by the Cas1-Cas2 integration complex. Although off-target spacer
      integration outside of canonical CRISPR arrays has been described in vitro, no
      evidence of non-specific integration activity has been found in vivo. Here, we
      show that non-canonical off-target integrations can occur within bacterial
      chromosomes at locations that resemble the native CRISPR locus by characterizing
      hundreds of off-target integration locations within Escherichia coli. Considering
      whether such promiscuous Cas1-Cas2 activity could have an evolutionary role
      through the genesis of neo-CRISPR loci, we combed existing CRISPR databases and
      available genomes for evidence of off-target integration activity. This search
      uncovered several putative instances of naturally occurring off-target spacer
      integration events within the genomes of Yersinia pestis and Sulfolobus
      islandicus. These results are important in understanding alternative routes to
      CRISPR array genesis and evolution, as well as in the use of spacer acquisition
      in technological applications.

PMID- 29379210
TI  - AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon
      signalling.
AB  - Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barre
      syndrome1,2. While progress has been made in understanding the causal link
      between ZIKV infection and microcephaly3-9, the life cycle and pathogenesis of
      ZIKV are less well understood. In particular, there are conflicting reports on
      the role of AXL, a TAM family kinase receptor that was initially described as the
      entry receptor for ZIKV10-22. Here, we show that while genetic ablation of AXL
      protected primary human astrocytes and astrocytoma cell lines from ZIKV
      infection, AXL knockout did not block the entry of ZIKV. We found, instead, that
      the presence of AXL attenuated the ZIKV-induced activation of type I interferon
      (IFN) signalling genes, including several type I IFNs and IFN-stimulating genes.
      Knocking out type I IFN receptor alpha chain (IFNAR1) restored the vulnerability
      of AXL knockout astrocytes to ZIKV infection. Further experiments suggested that
      AXL regulates the expression of SOCS1, a known type I IFN signalling suppressor,
      in a STAT1/STAT2-dependent manner. Collectively, our results demonstrate that AXL
      is unlikely to function as an entry receptor for ZIKV and may instead promote
      ZIKV infection in human astrocytes by antagonizing type I IFN signalling.

PMID- 29379211
TI  - Passive immunotherapy of viral infections: 'super-antibodies' enter the fray.
AB  - Antibodies have been used for more than 100 years in the therapy of infectious
      diseases, but a new generation of highly potent and/or broadly cross-reactive
      human monoclonal antibodies (sometimes referred to as 'super-antibodies') offers
      new opportunities for intervention. The isolation of these antibodies, most of
      which are rarely induced in human infections, has primarily been achieved by
      large-scale screening for suitable donors and new single B cell approaches to
      human monoclonal antibody generation. Engineering the antibodies to improve half
      life and effector functions has further augmented their in vivo activity in some
      cases. Super-antibodies offer promise for the prophylaxis and therapy of
      infections with a range of viruses, including those that are highly antigenically
      variable and those that are newly emerging or that have pandemic potential. The
      next few years will be decisive in the realization of the promise of super
      antibodies.

PMID- 29379214
TI  - Bacterial pathogenesis: Don't stress and repair the damage.

PMID- 29379217
TI  - Marine Microbiology: Climate change boosts cyanobacteria.

PMID- 29379216
TI  - Genome watch: Keeping tally in the microbiome.
AB  - This month's Genome Watch highlights how the development of new approaches for
      quantifying the human microbiome may pave the way for a better understanding of
      microbial shifts in the context of human health and disease.

PMID- 29379213
TI  - Epigenetic control of CD8+ T cell differentiation.
AB  - Upon stimulation, small numbers of naive CD8+ T cells proliferate and
      differentiate into a variety of memory and effector cell types. CD8+ T cells can
      persist for years and kill tumour cells and virally infected cells. The
      functional and phenotypic changes that occur during CD8+ T cell differentiation
      are well characterized, but the epigenetic states that underlie these changes are
      incompletely understood. Here, we review the epigenetic processes that direct
      CD8+ T cell differentiation and function. We focus on epigenetic modification of
      DNA and associated histones at genes and their regulatory elements. We also
      describe structural changes in chromatin organization that affect gene
      expression. Finally, we examine the translational potential of epigenetic
      interventions to improve CD8+ T cell function in individuals with chronic
      infections and cancer.

PMID- 29379212
TI  - NF-kappaB, inflammation, immunity and cancer: coming of age.
AB  - Fourteen years have passed since nuclear factor-kappaB (NF-kappaB) was first
      shown to serve as a molecular lynchpin that links persistent infections and
      chronic inflammation to increased cancer risk. The young field of inflammation
      and cancer has now come of age, and inflammation has been recognized by the broad
      cancer research community as a hallmark and cause of cancer. Here, we discuss how
      the initial discovery of a role for NF-kappaB in linking inflammation and cancer
      led to an improved understanding of tumour-elicited inflammation and its effects
      on anticancer immunity.

PMID- 29379215
TI  - Rhizobia: from saprophytes to endosymbionts.
AB  - Rhizobia are some of the best-studied plant microbiota. These oligotrophic
      Alphaproteobacteria or Betaproteobacteria form symbioses with their legume hosts.
      Rhizobia must exist in soil and compete with other members of the microbiota
      before infecting legumes and forming N2-fixing bacteroids. These dramatic
      lifestyle and developmental changes are underpinned by large genomes and even
      more complex pan-genomes, which encompass the whole population and are subject to
      rapid genetic exchange. The ability to respond to plant signals and
      chemoattractants and to colonize nutrient-rich roots are crucial for the
      competitive success of these bacteria. The availability of a large body of
      genomic, physiological, biochemical and ecological studies makes rhizobia unique
      models for investigating community interactions and plant colonization.

PMID- 29379218
TI  - Ecological Networks and Neighborhood Social Organization.
AB  - Drawing on the social disorganization tradition and the social ecological
      perspective of Jane Jacobs, the authors hypothesize that neighborhoods composed
      of residents who intersect in space more frequently as a result of routine
      activities will exhibit higher levels of collective efficacy, intergenerational
      closure, and social network interaction and exchange. They develop this approach
      employing the concept of ecological networks-two-mode networks that indirectly
      link residents through spatial overlap in routine activities. Using data from the
      Los Angeles Family and Neighborhood Survey, they find evidence that econetwork
      extensity (the average proportion of households in the neighborhood to which a
      given household is tied through any location) and intensity (the degree to which
      household dyads are characterized by ties through multiple locations) are
      positively related to changes in social organization between 2000-2001 and 2006
      2008. These findings demonstrate the relevance of econetwork characteristics
      heretofore neglected in research on urban neighborhoods-for consequential
      dimensions of neighborhood social organization.

PMID- 29379219
TI  - Sensitivity of Gravity Wave Fluxes to Interannual Variations in Tropical
      Convection and Zonal Wind.
AB  - Using an idealized model framework with high-frequency tropical latent heating
      variability derived from global satellite observations of precipitation and
      clouds, the authors examine the properties and effects of gravity waves in the
      lower stratosphere, contrasting conditions in an El Nino year and a La Nina year.
      The model generates a broad spectrum of tropical waves including planetary-scale
      waves through mesoscale gravity waves. The authors compare modeled monthly mean
      regional variations in wind and temperature with reanalyses and validate the
      modeled gravity waves using satellite- and balloon-based estimates of gravity
      wave momentum flux. Some interesting changes in the gravity spectrum of momentum
      flux are found in the model, which are discussed in terms of the interannual
      variations in clouds, precipitation, and large-scale winds. While regional
      variations in clouds, precipitation, and winds are dramatic, the mean gravity
      wave zonal momentum fluxes entering the stratosphere differ by only 11%. The
      modeled intermittency in gravity wave momentum flux is shown to be very realistic
      compared to observations, and the largest-amplitude waves are related to
      significant gravity wave drag forces in the lowermost stratosphere. This strong
      intermittency is generally absent or weak in climate models because of
      deficiencies in parameterizations of gravity wave intermittency. These results
      suggest a way forward to improve model representations of the lowermost
      stratospheric quasi-biennial oscillation winds and teleconnections.

PMID- 29379220
TI  - Tracking Health Inequalities from High School to Midlife.
AB  - Educational gradients in health status, morbidity, and mortality are well
      established, but which aspects of schooling produce those gradients is only
      partially understood. We draw on newly available data from the midlife follow-up
      of the High School and Beyond sophomore cohort to analyze the relationship
      between students' level of coursework in high school and their long-term health
      outcomes. We additionally evaluate the mediating roles of skill development,
      postsecondary attendance and degree attainment, and occupational characteristics.
      We find that students who took a medium- to high-level course of study in high
      school have better self-reported health and physical functioning in midlife, even
      net of family background, adolescent health, baseline skills, and school
      characteristics. The association partially operates through pathways into
      postsecondary education. Our findings have implications for both educational
      policy and research on the educational gradient in health.

PMID- 29379221
TI  - Act-Frequency Signatures of the Big Five.
AB  - The traditional focus of work on personality and behavior has tended toward
      "major outcomes" such as health or antisocial behavior, or small sets of
      behaviors observable over short periods in laboratories or in convenience
      samples. In a community sample, we examined a wide set (400) of mundane,
      incidental or "every day" behavioral acts, the frequencies of which were reported
      over the past year. Using an exploratory methodology similar to genomic
      approaches (relying on the False Discovery Rate) revealed 26 prototypical acts
      for Intellect, 24 acts for Extraversion, 13 for Emotional Stability, nine for
      Conscientiousness, and six for Agreeableness. Many links were consistent with
      general intuition-for instance, low Conscientiousness with work and
      procrastination. Some of the most robust associations, however, were for acts too
      specific for a priori hypothesis. For instance, Extraversion was strongly
      associated with telling dirty jokes, Intellect with "loung[ing] around [the]
      house without clothes on", and Agreeableness with singing in the shower.
      Frequency categories for these acts changed with markedly non-linearity across
      Big Five Z-scores. Findings may help ground trait scores in emblematic acts, and
      enrich understanding of mundane or common behavioral signatures of the Big Five.

PMID- 29379222
TI  - Heparanase Overexpresses in Keratoconic Cornea and Tears Depending on the
      Pathologic Grade.
AB  - Background: Keratoconus has classically been defined as a noninflammatory
      disorder, although recent studies show elevated levels of inflammatory markers
      suggesting that keratoconus could be, at least in part, an inflammatory
      condition. Heparanase upregulation has been described in multiple inflammatory
      disorders. In this article, we study the differential expression of heparanase in
      cornea and tears from keratoconus patients and healthy controls. Methods: A
      transcriptomic approach was used employing quantitative polymerase chain reaction
      to analyze the expression of heparanase and heparanase 2 in stromal and
      epithelial corneal cells. The protein expression was analyzed by
      immunohistochemistry in corneal sections. Enzymatic activity in tears was
      measured using [3H]-labeled heparan sulfate as substrate. Results: Heparanase
      transcription was detected in stromal and epithelial cells and appeared
      upregulated in keratoconus. Overexpression of the enzyme was also detected by
      immunohistochemistry. Corneal expression of heparanase 2 was detected in some
      cases. Heparanase catalytic activity was found in tears and displayed a positive
      correlation with the degree of keratoconus. Conclusions: Heparanase overexpresses
      in keratoconic corneas, possibly reinforcing the inflammatory condition of the
      pathology. The presence of heparanase activity in tears allows us to propose its
      use as a biomarker for the diagnosis of the disorder.

PMID- 29379223
TI  - Prognostic Association of Circulating Neutrophil Count with No-Reflow in Patients
      with ST-Segment Elevation Myocardial Infarction following Successful Primary
      Percutaneous Intervention.
AB  - Objective: The aim of the present study was to investigate the predictive value
      of neutrophil count for no-reflow in patients with ST-segment elevation
      myocardial infarction (STEMI) who underwent successful primary percutaneous
      intervention (PCI). Methods: We conducted a retrospective study of 361 patients
      diagnosed with acute STEMI between 2011 and 2015. All patients underwent
      successful PCI within 12 h from the onset of symptoms. Angiographic no-reflow was
      diagnosed based on a post-PCI thrombolysis in myocardial infarction flow grade <=
      2 without mechanical obstruction. According to a neutrophil count cut-off
      determined by receiver operating characteristic curve analysis, patients were
      divided into two groups: group A (neutrophil count < 9.14 * 109/L) and group B
      (neutrophil count >= 9.14 * 109/L). Results: Compared to patients in the normal
      reflow group, patients with no-reflow had higher neutrophil counts (P < 0.05).
      The incidence rate of no-reflow in group A (18, 9.3%) was significantly lower
      than that in group B (38). Multivariate logistic regression analysis revealed
      that a neutrophil count >= 9.14 * 109/L was independently predictive for no
      reflow (odds ratio = 4.474, 95% confidence interval: 1.610-12.433, P = 0.004)
      after adjusting for potential confounders. Conclusions: A circulating neutrophil
      count >= 9.14 * 109/L is independently associated with no-reflow in patients with
      acute STEMI following primary PCI.

PMID- 29379224
TI  - Implicit learning of structure occurs in parallel with lexically-mediated
      syntactic priming effects in sentence comprehension.
AB  - The aim of this study was to determine whether cumulative structural priming
      effects and trial-to-trial lexically-mediated priming effects are produced by the
      same mechanism in comprehension. Participants took part in a five-session eye
      tracking study where they read reduced-relative prime-target pairs with the same
      initial verb. Half of the verbs in these sentences were repeated across the five
      sessions and half were novel to each session. Total fixation times on the
      syntactically challenging parts of prime sentences decreased across sessions,
      suggesting participants implicitly learned the structure. Additional priming was
      also observed at the critical regions of the target sentences, and the magnitude
      of this effect did not change over the five sessions. These finding suggests long
      lived adaptation to structure and short-lived lexically-mediated priming effects
      are caused by separate mechanisms in comprehension. A dual mechanism account of
      syntactic priming effects can best reconcile these results.

PMID- 29379225
TI  - Hylleraas-Configuration Interaction study of the 1S ground state of the negative
      Li ion.
AB  - In a previous work Sims and Hagstrom [J. Chem. Phys. 140, 224312 (2014)] reported
      Hylleraas-Configuration Interaction (Hy-CI) method variational calculations for
      the neutral atom and positive ion 1S ground states of the beryllium isoelectronic
      sequence. The Li- ion, nominally the first member of this series, has a decidedly
      different electronic structure. This paper reports the results of a large,
      comparable calculation for the Li- ground state to explore how well the Hy-CI
      method can represent the more diffuse L shell of Li- which is representative of
      the Be(2sns) excited states as well. The best non-relativistic energy obtained
      was -7.500 776 596 hartree, indicating that 10 - 20 nh accuracy is attainable in
      Hy-CI and that convergence of the r12r34 double cusp is fast and that this
      correlation type can be accurately represented within the Hy-CI model.

PMID- 29379226
TI  - Pet Dogs: Does their presence influence preadolescents' emotional responses to a
      social stressor?
AB  - Despite interest in human-animal interaction, few studies have tested whether the
      presence of a dog facilitates children's emotional responding. Preadolescents (n
      = 99) were randomly assigned to complete the Trier Social Stress Test either with
      or without their pet dog. Children rated their positive and negative affect, and
      high frequency heart rate variability (HF-HRV) was assessed throughout the
      session. Children reported higher positive affect when they completed the task
      with their pet dog, although there were no differences for negative affect or HF
      HRV. Children who had more physical contact with their dog at baseline reported
      higher positive affect. The findings suggest contact with pets is associated with
      enhanced positive affect.

PMID- 29379229
TI  - Redefining radiology senior residency - Can we provide an alternative to "The
      Consultant Job".

PMID- 29379227
TI  - Gene Expression, Oxidative Stress, and Senescence of Primary Coronary Endothelial
      Cells Exposed to Postprandial Serum of Healthy Adult and Elderly Volunteers after
      Oven-Cooked Meat Meals.
AB  - Epidemiological studies have linked high consumption of meat with major age
      related diseases including cardiovascular diseases. Abnormal postprandial
      increases in plasma lipids after a meat meal have been hypothesized among the
      pathogenetic mechanisms. However, it is still unknown if the postprandial serum
      derived after a normal meat meal is able to affect endothelial function, and if
      the type of meat and the age of the donors are critical factors. Here, we show
      the effects of postprandial sera derived from healthy adults and elderly
      volunteers who consumed meat meals on human coronary artery endothelial cell
      (HCAEC) oxidative stress, gene expression, DNA damage, and cellular senescence.
      We observed that a single exposure to postprandial serum induces a slight
      increase in ROS that is associated with modulation of gene expression pathways
      related to oxidative stress response and metabolism. The postprandial-induced
      increase in ROS is not associated with a measurable DNA oxidative damage.
      However, repeated exposure to postprandial serum induces an acceleration of
      cellular senescence. Taking into account the deleterious role of cellular
      senescence in age-related vascular diseases, the results suggest a new mechanism
      by which excessive meat consumption and time spent in postprandial state may
      affect health status during aging.

PMID- 29379230
TI  - Dilemma of diagnosing thoracic sarcoidosis in tuberculosis endemic regions: An
      imaging-based approach. Part 1.
AB  - Sarcoidosis is a multi-systemic disorder of unknown etiology, although commonly
      believed to be immune-mediated. Histologically, it is characterized by
      noncaseating granuloma which contrasts against the caseating granuloma seen in
      tuberculosis (TB), an infectious disease that closely mimics sarcoidosis, both
      clinically as well as radiologically. In TB-endemic regions, the overlapping
      clinico-radiological manifestations create significant diagnostic dilemma,
      especially since the management options are markedly different in the two
      entities. Part 1 of this review aims to summarize the clinical, laboratory, and
      imaging features of sarcoidosis, encompassing both typical and atypical
      manifestations, in an attempt to distinguish between the two disease entities.

PMID- 29379228
TI  - Small Intestinal Bacterial Overgrowth Affects the Responsiveness to Colchicine in
      Familial Mediterranean Fever.
AB  - Objective: Familial Mediterranean fever (FMF) is an autosomal recessive disease
      due to a MEFV gene mutation. Since Helicobacter pylori infection has been
      described to increase the severity and frequency of FMF attacks, we evaluate if
      overgrowth of small intestinal bacterial (SIBO), associated with a release of
      bacterial products, can affect the response to colchicine in FMF patients poorly
      responsive to colchicine. Methods: We revised our Periodic Fever Centre database
      to detect FMF patients who were poorly responsive to colchicine, without a well
      defined cause of drug resistance. They were evaluated for SIBO presence, then
      treated with decontamination therapy. Results: Among 223 FMF patients, 49
      subjects show colchicine resistance, and no other known causes of colchicine
      unresponsiveness has been found in 25 patients. All 25 patients underwent glucose
      breath test; 20 (80%) of them were positive, thus affected by SIBO. After a
      successful decontamination treatment, 11 patients (55%) did not show FMF attacks
      during the following three months (p < 0.01), while 9 of them revealed a
      significant reduction of the number of attacks compared to three months before (p
      < 0.01). Conclusion: The SIBO eradication improves laboratory and clinical
      features of FMF patients. Thus, patients with unresponsiveness to colchicine
      treatment should be investigated for SIBO.

PMID- 29379231
TI  - Dilemma of diagnosing thoracic sarcoidosis in tuberculosis-endemic regions: An
      imaging-based approach. Part 2.
AB  - The second part of the review discusses the role of different existing imaging
      modalities in the evaluation of thoracic sarcoidosis, including chest radiograph,
      computed tomography, magnetic resonance imaging, endobronchial ultrasound, and
      positron emission tomography. While summarizing the advantages and pitfalls of
      each imaging modality, the authors propose imaging recommendations and an
      algorithm to be followed in the evaluation of clinically suspected case of
      sarcoidosis in tuberculosis-endemic regions.

PMID- 29379232
TI  - Appraisal of radiation dose with 64-slice computed tomography perfusion in lung
      cancer patients with special reference to SSDE: An initial experience in a
      tertiary care hospital.
AB  - Context: Computed tomography perfusion (CTP) is an important functional tool for
      lung cancer. It is expected to deliver high radiation dose, making its accurate
      estimation important. Size-specific dose estimate (SSDE) is a new dose metric,
      which includes the scanner output as well as the patient size. Aims: To determine
      radiation dose [CT dose index (CTDIvol), dose length product (DLP), effective
      dose (ED), and SSDE] for CTP in lung cancer and the correlation of CTDIvol, DLP,
      and SSDE with effective diameter and SSDE with weight, body mass index (BMI), and
      the scan length. Settings and Design: Cross-sectional study in the Department of
      Radio-diagnosis from October 2015 to March 2016. Patients and Methods: Due
      ethical approval and informed consent was taken. Thirty consecutive adult
      patients of lung cancer undergoing CTP study were included; various radiation
      dose parameters were determined and presented as mean +/- SD. Statistical
      Analysis Used: Paired Student's t-test and Pearson correlation using Statistical
      Package for the Social Sciences, Version 16. Results: Mean radiation dose was
      CTDIvol = 270.138 +/- 1.627 mGy, DLP = 681 +/- 53.496 mGy.cm, ED = 12.501 +/-
      0.923 mSv, SSDE = 388.90 +/- 81.27 mGy. The CTDIvol and DLP had significant
      positive correlation (r = 0.556, P = 0.000 and r = 0.522, P = 0.003,
      respectively) with effective diameter. SSDE had strong negative correlation (r = 
      0.997, P = 0.000) with effective diameter, significant negative correlation with
      the BMI (r = -0.889; P = 0.000) and weight (r = -0.910, P = 0.000) of patients.
      Scan length was not significantly correlated in SSDE (r = -0.012, P = 0.951).
      Conclusions: Smaller sized patients had greater SSDE.

PMID- 29379233
TI  - Radiological spectrum of anthracofibrosis: A series of 40 patients with computed
      tomography, bronchoscopy, and biopsy.
AB  - Introduction: Anthracofibrosis is a lesser known clinical entity. Patients
      present with chronic symptoms of cough and breathlessness with a history of
      biofuel/wood fire smoke exposure. There are distinct computed tomography (CT)
      imaging features of anthracofibrosis that can differentiate it from more common
      conditions such as tuberculosis (TB) and bronchogenic carcinoma. Findings include
      multifocal noncontiguous stenosis of bronchial tree, calcified enlarged
      mediastinal or hilar nodes, and secondary lung parenchymal changes. However, in
      TB, bronchostenosis usually involves a single lobar bronchus in a contiguous
      manner with trachea and/or major bronchi also being affected. In this study, we
      highlight the imaging characteristics of anthracofibrosis. Context: The CT
      findings of anthracofibrosis closely mimic TB and bronchogenic carcinoma, hence
      we highlight the key imaging features of anthracofibrosis. Aims and Objectives:
      To identify and describe the CT imaging features of anthracofibrosis and
      correlate it with bronchoscopic findings. Setting and Design: Retrospective
      study. Materials and Methods: Retrospectively, 40 patients were selected who were
      diagnosed with anthracofibrosis on bronchoscopy and biopsy. However, CT scan
      records of only 14 patients were available for review. Two radiologists reviewed
      the scans independently. Results: Most common CT finding was multisegmental
      noncontiguous bronchostenosis seen in 93% patients mostly involving the right
      middle lobe. 85% of the cases showed lymph node enlargement involving hilar,
      peribronchial, and mediastinal nodes. The nodes were calcified in 91.7% of the
      cases, with 58% showing pressure effect on adjacent bronchi due to nodal
      enlargement. The next common findings were peribronchial cuffing and bronchial
      obstruction seen in 57 and 28% of the cases, respectively. Conclusion: The key
      imaging features of anthracofibrosis on CT are multifocal involvement of bronchi
      with smooth peribronchial thickening and enlarged calcified lymph nodes.

PMID- 29379235
TI  - Levoatrial cardinal vein with normal left ventricle: A forgotten cause of
      pulmonary arterial hypertension.
AB  - Levoatrial cardinal vein (LACV) is anomalous connection between left atrium or
      pulmonary veins and systemic veins such as innominate vein or superior vena cava.
      This persistence of splanchnic circulation occurs when there is left-sided
      obstructive cardiac lesions such as hypoplastic left heart or mitral atresia. In
      this report we present three cases of LACV with well-developed left heart,
      without any obstructive lesions. All our cases presented with pulmonary arterial
      hypertension (PAH) and had associated intracardiac shunt such as
      ventricular/atrial septal defect and supracardiac partial anomalous pulmonary
      venous connection. Apart from the above shunts, LACV contributed to PAH in these
      cases. It is important to detect and report LACV as this may require surgical
      correction along with other defects. If LACV goes undetected during imaging
      workup, it may cause persistent PAH postoperatively.

PMID- 29379234
TI  - Cardiac magnetic resonance techniques: Our experience on wide bore 3 tesla
      magnetic resonance system.
AB  - Cardiovascular magnetic resonance (CMR) has become a widely adapted imaging
      modality in the diagnosis and management of patients with cardiovascular
      diseases. It provides unparalleled data of cardiac function and myocardial
      morphology. Majority of CMR imaging is currently being performed on 1.5 Tesla (T)
      MR systems. Over the last many years, the cardiac imaging protocols have been
      standardized and optimized in the 1.5T systems. 3T MR systems are now being used
      more and more in small and large institutions in our country due to their proven
      advantages in the field of neuro, body, and musculoskeletal imaging. Cardiac
      imaging on 3T system can be a double-edged sword. On one hand, it may provide
      nondiagnostic images due to significant artifacts, and on the other hand, it may
      complete the examination in quick time and provide excellent quality images. It
      is therefore important for the user to be aware of the potential pitfalls of CMR
      in 3T systems and also the necessary steps to avoid them. In this study, we
      discuss various challenges and advantages of performing CMR in a 3T system. We
      also present potential technical solutions to improve the image quality.

PMID- 29379236
TI  - Spinal dysraphism illustrated; Embroyology revisited.
AB  - Spinal cord development occurs through three consecutive periods of gastrulation,
      primary nerulation and secondary neurulation. Aberration in these stages causes
      abnormalities of the spine and spinal cord, collectively referred as spinal
      dysraphism. They can be broadly classified as anomalies of gastrulation
      (disorders of notochord formation and of integration); anomalies of primary
      neurulation (premature dysjunction and nondysjunction); combined anomalies of
      gastrulation and primary neurulation and anomalies of secondary neurulation.
      Correlation with clinical and embryological data and common imaging findings
      provides an organized approach in their diagnosis.

PMID- 29379237
TI  - Intracranial translucency as a sonographic marker for detecting open spina bifida
      at 11-13+6 weeks scan: Our experience.
AB  - Aims and Objectives: The fourth ventricle, seen as intracranial translucency (IT)
      at 11-13+6 weeks, has been reported to be obliterated in cases of open spina
      bifida (OSB). Our aim was to assess its role in detecting OSB at 11-13+6 weeks.
      Materials and Methods: This prospective study was conducted at foetal medicine
      unit from January 2014 to June 2015. All women who underwent both first and mid
      trimester scan in our unit were included in the study. IT was categorized as
      normal, obliterated or not clear. Spine was examined during both scans. Results:
      Totally, 341 cases were included in the study. IT was found to be obliterated in
      four cases and not clear in one case. There was demonstrable OSB at 11-13+6 weeks
      in two cases, at 15-16 weeks in two cases and at 24 weeks in one case. In the
      remaining 336 cases with normal IT, spine was found to be normal at target scan.
      Conclusion: Mid-sagittal view of face that is routinely used to measure nuchal
      translucency (NT) can also be used to detect OSB. It is feasible to integrate IT
      into the routine 11-13+6 weeks scan.

PMID- 29379238
TI  - Emergent presentation of Langerhans cell histiocytosis in a pediatric patient:
      Acute cerebellar involvement causing obstructive hydrocephalus requiring
      posterior fossa decompression.
AB  - Langerhans cell histiocytosis (LCH) is a disorder of the monocyte-macrophage
      system that can be unifocal or systemic. Here, we present a pediatric case who
      initially presented with osseous LCH but again presented 6 years later emergently
      with cerebellar symptoms, cerebellar mass and obstructive hydrocephalus. Patient
      underwent biopsy of the cerebellum which was path proven intracranial LCH.

PMID- 29379239
TI  - A rare case of OEIS complex - newer approach to diagnosis of exstrophy bladder by
      color doppler and its differentiation from simple omphalocele.
AB  - The objective of this article is to present a new approach to diagnose and
      differentiate similar ventral masses by color Doppler. Two cases of ventral
      masses, a rare case of OEIS complex (Omphalocele-exstrophy-imperforate anus
      spinal defects) with unusual presentation of exstrophy bladder and another of
      simple omphalocele, were studied by color Doppler for diagnosis and
      differentiation between the nature of similar masses. Ventral mass with absent
      bladder, normal kidneys, and normal amniotic fluid index raised the suspicion of
      exstrophy bladder. Color Doppler depicting altered intrafetal course of umbilical
      arteries and umbilical arteries coursing along the sides of ventral mass
      substantiated the diagnosis. The spatial relation between umbilical artery and
      aorta (which has no mention in the current literature) in sagittal view has been
      identified as an acute angle in a normal fetus and coined as "K angle"
      arbitrarily by the author. Color Doppler reveals altered (widened) "K angle" in
      exstrophy bladder compared to normal fetuses. Other combined anomalies pointed to
      the diagnosis of OEIS complex. The second case of simple omphalocele depicts
      normal intrafetal course of umbilical arteries and normal acute umbilical artery
      aorta angle (K angle) on color Doppler. Color Doppler aids the early diagnosis of
      ventral defects. New method by umbilical artery-aorta angle (K angle) assessment
      on color Doppler helps differentiate exstrophy bladder from omphalocele.

PMID- 29379240
TI  - Imaging review of cerebrospinal fluid leaks.
AB  - Cerebrospinal fluid (CSF) leak occurs due to a defect in the dura and skull base.
      Trauma remains the most common cause of CSF leak; however, a significant number
      of cases are iatrogenic, and result from a complication of functional endoscopic
      sinus surgery (FESS). Early diagnosis of CSF leak is of paramount importance to
      prevent life-threatening complications such as brain abscess and meningitis.
      Imaging plays a crucial role in the detection and characterization of CSF leaks.
      Three-dimensional, isotropic, high resolution computed tomography (HRCT)
      accurately detects the site and size of the bony defect. CT cisternography,
      though invasive, helps accurately identify the site of CSF leak, especially in
      the presence of multiple bony defects. Magnetic resonance imaging (MRI)
      accurately detects CSF leaks and associated complications such as the
      encephaloceles and meningoceles. In this review, we emphasize the importance and
      usefulness of 3D T2 DRIVE MR cisternography in localizing CSF leaks. This
      sequence has the advantages of effective bone and fat suppression, decreased
      artefacts, faster acquisition times, three-dimensional capability, y and high
      spatial resolution in addition to providing very bright signal from the CSF.

PMID- 29379241
TI  - Comparison of fractional anisotropy and apparent diffusion coefficient among
      hypoxic ischemic encephalopathy stages 1, 2, and 3 and with nonasphyxiated
      newborns in 18 areas of brain.
AB  - Purpose: To determine the area and extent of injury in hypoxic encephalopathy
      stages by diffusion tensor imaging (DTI) using parameters apparent diffusion
      coefficient (ADC) and fractional anisotropy (FA) values and their comparison with
      controls without any evidence of asphyxia. To correlate the outcome of hypoxia
      severity clinically and significant changes on DTI parameter. Materials and
      Methods: DTI was done in 50 cases at median age of 12 and 20 controls at median
      age of 7 days. FA and apparent diffusion coefficient (ADC) were measured in
      several regions of interest (ROI). Continuous variables were analyzed using
      Student's t-test. Categorical variables were compared by Fisher's exact test.
      Comparison among multiple groups was done using analysis of variance (ANOVA) and
      post hoc Bonferroni test. Results: Abnormalities were more easily and accurately
      determined in ROI with the help of FA and ADC values. When compared with controls
      FA values were significantly decreased and ADC values were significantly
      increased in cases, in ROI including both right and left side of thalamus, basal
      ganglia, posterior limb of internal capsule, cerebral peduncle, corticospinal
      tracts, frontal, parietal, temporal, occipital with P value < 0.05. The extent of
      injury was maximum in stage-III. There was no significant difference among males
      and females. Conclusion: Compared to conventional magnetic resonance imaging
      (MRI), the evaluation of FA and ADC values using DTI can determine the extent and
      severity of injury in hypoxic encephalopathy. It can be used for early
      determination of brain injury in these patients.

PMID- 29379242
TI  - Diffusion tensor imaging metrics in cystic intracranial mass lesions.
AB  - Background and Purpose: Conventional MR does not always differentiate various
      cystic lesions of brain. Our purpose was to explore the utility of DTI in
      characterization & differentiation of intra cranial cystic mass lesions.
      Materials and Methods: DTI was done with a clinical 1.5 Tesla system in 62
      patients presenting with intra cranial cystic lesions. Parameter maps of the DTI
      metrics MD, FA, GA, RA, Geometric tensors (CL,CP,CS) were calculated & quantified
      using regions of interest. Cystic lesions were grouped based on etiology and
      management. Statistical analysis was performed to test the significance of
      difference in DTI metrics in differentiation of various groups of cystic lesions
      of brain. Results: Mann-Whitney U Test was done to analyse the usefulness of
      various DTI metrics in differentiating the intracranial cysts. Epidermoid cysts
      showed highest FA, RA, Cl & Cp due to the preferential diffusion of water through
      the well structured orientation of keratin filaments & flakes within it.
      Neurocysticercosis showed higher FA, next to epidermoid. Abscesses showed lowest
      MD. Arachanoid cyst, giant cistern magna, choroid fissure cyst, choroid plexus
      cyst, ependymal & neuroglial cysts showed higher MD & lower FA, implicating no
      preferential directional diffusivity. Conclusion: DTI does prove useful in
      characterization and differentiation of intracranial cystic mass lesions. This
      study implicates the need for inclusion of DTI in the routine protocol of imaging
      cystic intracranial mass lesions.

PMID- 29379243
TI  - Evaluation of parenchymal thyroid diseases with multiparametric ultrasonography.
AB  - Aim: Differential diagnosis of parenchymal thyroid diseases by gray-scale
      ultrasound is quite difficult for a radiologist as the findings are very similar
      to each other. In this study we aimed to assess some quantitative spectral
      Doppler parameters, resistivity index (RI), acceleration time (AT), and
      quantitative elastography [shear wave velocity (SWV)] together to show their
      reliability for differential diagnosis of parenchymal thyroid diseases. Materials
      and Methods: We retrospectively reviewed findings of 227 patients (179 females,
      48 males) that underwent spectral Doppler ultrasound and acoustic radiation force
      impulse between October 2013 and March 2016. Ages of the patients were between 18
      and 74 years (39.52 +/- 12.67). Based on clinical and laboratory findings,
      patients were divided into five groups (N: Normal, EH: Early Hashimoto, H: Late
      Hashimoto, M: Nodular Thyroid Disease, HM: Hashimoto + Nodular Thyroid Disease).
      Detailed statistical analyses were done on parameters such as age, gender, volume
      information, and RI, AT (ms), SWV (m/s). Results: No significant effect of gender
      or volume on the differentiation of disease pattern (Chi-square test: P = 0.306,
      Kruskal-Wallis test: P = 0.290) was found in this study. RI (0.41 +/- 0.06) and
      SWV values (1.19 +/- 0.18 m/s) were the lowest. AT values (>55 ms) were the
      highest in EH group (area under the curve: 0.913). Existence of H decreased RI
      and SWV values, while it extended AT in a different thyroid disease. Conclusion:
      Thyroid parenchymal diseases could be classified and differentiated from each
      other by measuring RI, AT, and SWV values quantitatively. So, in suspicious
      cases, these parameters could be a reliable asset for differential diagnosis.

PMID- 29379245
TI  - Role of transperineal ultrasound in infective and inflammatory disorders.
AB  - Aims: To evaluate the role of transperineal ultrasound as screening tool in
      infective and inflammatory diseases of perianal region. Materials and Methods:
      Initially, clinical examination of the perineal region of patients (pts) for
      perianal external opening of tracts, swelling and tenderness is done. The
      perineal USG was performed using 2 -5 MHz sector probe and 7 -13 MHz linear probe
      on GE logiq P 5 ultrasound machine. Internal opening of any fistulous tract were
      described with clockwise position and tracts were traced upto their external
      opening and perifocal area were screened for any ramification. The Park et al.
      classification was used for classifying the tracts. Results: Out of 492 pts, 60
      pts were normal, 257 pts had fistula, 114 pts had sinuses, 44 pts had only
      abscess without fistula or sinus and 17 pts had other pathologies with 95%
      sensitivity (Sn), 100% specificity (Sp) and Positive Predictive Value (PPV) and
      95% Negative Predictive Value (NPV) for fistula and 94% Sn, 97% Sp, 89% PPV and
      98% NPV for active sinuses and 98% Sp, 96% ppv and 100% NPV and Sn for abscesses.
      Conclusions: Transperineal Ultrasound should be performed as first line imaging
      modality for suspicion of low perianal fistula with high sensitivity,
      specificity, and negative predictive value at much lower cost and less time as
      compared to perineal MRI.

PMID- 29379244
TI  - Review of imaging in post-laparoscopy cholecystectomy complications.
AB  - Laparoscopic cholecystectomy is now considered the procedure of choice for
      uncomplicated symptomatic gallstone disease worldwide. Various biliary, vascular,
      gastrointestinal, neurological and local complications may be seen on imaging
      post surgery. Knowledge of these entities and imaging appearances is
      indispensable for the radiologist in today's era. We emphasize on the list of
      potential complications and imaging appearances of this surgical procedure.

PMID- 29379246
TI  - Endovascular uterine artery interventions.
AB  - Percutaneous vascular embolization plays an important role in the management of
      various gynecologic and obstetric abnormalities. Transcatheter embolization is a
      minimally invasive alternative procedure to surgery with reduced morbidity and
      mortality, and preserves the patient's future fertility potential. The clinical
      indications for transcatheter embolization are much broader and include many
      benign gynecologic conditions, such as fibroid, adenomyosis, and arteriovenous
      malformations (AVMs), as well as intractable bleeding due to inoperable advanced
      stage malignancies. The most well-known and well-studied indication is uterine
      fibroid embolization. Uterine artery embolization (UAE) may be performed to
      prevent or treat bleeding associated with various obstetric conditions, including
      postpartum hemorrhage (PPH), placental implantation abnormality, and ectopic
      pregnancy. Embolization of the uterine artery or the internal iliac artery also
      may be performed to control pelvic bleeding due to coagulopathy or iatrogenic
      injury. This article discusses these gynecologic and obstetric indications for
      transcatheter embolization and reviews procedural techniques and outcomes.

PMID- 29379247
TI  - Radiofrequency ablation of surface v/s intraparenchymal hepatocellular carcinoma
      in cirrhotic patients.
AB  - Objective: To retrospectively evaluate the safety and technical efficacy of
      percutaneous radiofrequency ablation (RFA) of surface hepatocellular carcinoma
      (HCC) in comparison to intraparenchymal HCC in cirrhotic patients. Materials and
      Methods: Surface lesions were defined as tumours located or reaching within 1cm
      of liver capsule including exophytic lesions. Seventy-four surface HCC including
      21 exophytic in 58 patients (surface group) and 60 intraparenchymal HCC in 54
      patients (intraparenchymal group) measuring up to 4 cm in maximum extent
      underwent percutaneous [ultrasound (US) or computed tomography-guided (CT
      guided)] RFA. The response to the treatment was assessed by contrast enhanced
      CT/magnetic resonance imaging (MRI) done at 1, 3, 6, 9, and 12 months of RFA and
      thereafter every 4-6 months. In case of features suggesting residual disease, a
      repeat RFA was performed. The technical success after single-session RFA,
      complications and disease recurrence rates were calculated and compared between
      two groups. Results: Technical success achieved after first session of RFA in
      surface HCC was 95% (70/74) and intraparenchymal HCC was 97% (58/60). Hundred
      percent secondary success rate was achieved in both groups after second repeat
      RFA in residual lesion. No major difference in complication and local recurrence
      rate in both group on follow-up in surface HCC and intraparenchymal HCC. No case
      of needle track, peritoneal seeding, and treatment mortality was found.
      Conclusions: The complication rate and efficacy of RFA for surface and exophytic
      HCC's were comparable to that of intraparenchymal HCC. Hence surface and
      exophytic lesions should not be considered a contraindication for RFA in
      cirrhotic patients.

PMID- 29379248
TI  - Abdominal aorta aneurysm with hostile neck: Early outcomes in outside instruction
      for use in patients using the treovance(r) stent graft.
AB  - Purpose: The efficacy and safety of endovascular aneurysm repair (EVAR), in
      patients outside instruction for use (IFU), is very challenging and widely
      debated. The aim of this study was to evaluate the placement of the Treovance(r)
      abdominal aorta stent-graft in patients with hostile proximal necks considered
      outside IFU. Materials and Methods: Between May 2013 and August 2014, 5 patients
      with outside IFU underwent EVAR with the Treovance(r) stent-graft. Technical and
      clinical successes were evaluated. All 5 patients underwent clinical and imaging
      follow-up. Results: Technical and clinical successes were achieved in all 5
      patients without adjunctive endovascular procedures or surgical conversion.
      During the mean follow-up of 21 months, no type I/III endoleaks, stent-graft
      migration nor kinking/occlusion were observed. In all 5 patients, a reduction of
      the proximal neck angle was observed. Conclusion: In our small series of selected
      outside IFU patients, EVAR with the Treovance(r) stent-graft was technically
      feasible and safe, with satisfactory short-term follow-up results, when performed
      by experienced operators. Long-term follow-up will be necessary to confirm the
      durability of our preliminary promising results.

PMID- 29379250
TI  - Informed consent in diagnostic radiology practice: Where do we stand?
AB  - We review the evolution of the concept of informed consent from a radiology
      standpoint, the current international guidelines on the need for obtaining
      consent in diagnostic radiology practice, and the current Indian scenario,
      focusing on both practical and medicolegal aspects. We discuss the concept of
      patient information sheet with signature, a potential way forward benefiting both
      patients and radiologists.

PMID- 29379249
TI  - Is there a clinical usefulness for radiolabeled somatostatin analogues beyond the
      consolidated role in NETs?
AB  - The somatostatin (SS) receptor scintigraphy (SRS), using octreotide radiolabelled
      with 111In (Ocreoscan(c), OCT), is a consolidated diagnostic procedure in
      patients with neuroendocrine tumors (NET) because of an increased expression of
      somatostatin receptors (SS-R) on neoplastic cells. Uptake of SS analogues (SSA)
      can also be due to SS-R expression on nonmalignant cells when activated as
      lymphocytes, macrophages, fibroblasts, vascular cells. Because of this uptake,
      clinical indications can be found either in neoplasms not overexpressing SS-R, as
      nonsmall cell lung cancer, and in active benign diseases. Nevertheless, clinical
      application of SRS has not found clinical relevance yet. In this paper, we
      discuss the nononcologic fields of clinical interest in which SRS could play a
      clinical role such as diagnosis, prognosis, and therapy of benign and chronic
      diseases such as sarcoidosis, histiocytosis, rheumatoid arthritis, idiopathic
      pulmonary fibrosis, and Graves' ophthalmopathy.

PMID- 29379251
TI  - Transcatheter embolization of a cystic artery pseudoaneurysm in a cirrhotic
      patient with perforated acute cholecystitis.

PMID- 29379252
TI  - Ground reaction vector re-adjustment-the secret of success in treatment of medial
      compartment knee osteoarthritis by novel high fibular osteotomy.
AB  - High fibular osteotomy has been preliminarily proved to be an effective treatment
      of knee osteoarthritis by excising a segment of bone at the proximal part of
      fibula. This imaginative procedure is clinical validated by its instant and
      explicit knee pain resorption and eventually deformity correction. The rationale
      of this treatment is named non-uniform settlement of the tibial plateau and used
      to elucidate the cause of knee joint degeneration, but cannot illuminate the
      reason of prompt postoperative pain resorption faithfully. To assist in better
      understanding of this therapeutic method and raising alert to possible unexpected
      complications, we proposed a new theory to elucidate the pain relief mechanism.

PMID- 29379253
TI  - Templating in uncemented THA. On accuracy and postoperative leg length
      discrepancy.
AB  - Purpose: This study examines the accuracy of digital templating in uncemented
      total hip arthroplasty (THA), i.e., whether the templated components where
      actually inserted during surgery. The surgical outcome was evaluated on the basis
      of limb length equality. Methods: We retrospectively examined digital x-rays of
      41 patients scheduled for uncemented THA. These were templated using templating
      software. The template was compared to the surgical choice of implant registered
      in the patients' journal. Postoperative x-rays were evaluated for limb length
      equality. The data underwent statistical analysis to assess accuracy. Results:
      The acetabular component was templated accurately in 7.3%, while 41% was within
      +/- 1 component size difference, and 73% was within +/-2 size differences. The
      femoral stem was templated accurately in 34%, while 76% was within +/- 1
      component size difference, and 90% was within +/-2 size differences. The neck
      length was templated accurately in 29%, while 88% was within +/-1 component size
      difference, and 100% was within +/-2 size differences.Fifty four percent of
      patients experienced radiologic equalization within +/- 5 mm, and 85% within 10
      mm. Fifteen percent had leg length discrepancy of more than 10 mm
      postoperatively. There was no systematic tendency to overestimate or
      underestimate leg length peroperatively. Conclusions: We find that the accuracy
      of digital templating in uncemented THA is acceptable for the femoral stem, but
      somewhat inferior for the acetabular shell and poor for neck length. Templating
      is a useful tool in preoperative planning, but cannot be regarded as a blueprint
      for the operative choice.

PMID- 29379254
TI  - Inadvertent hypothermia in hip and knee total joint arthroplasty.
AB  - Background: This clinical study aims to establish rates of inadvertent
      hypothermia (IH) in both primary and revision total hip/knee arthroplasty
      (THA/TKA and rTHA/rTHA). We postulate differences exist between demographic,
      surgical and anesthetic variables and outcomes for IH and normothermic patients.
      Methods: We conducted a single centre, retrospective study of 2431 total joint
      arthroplasty (TJA) patients having undergone THA (n = 1096), TKA (n = 1083), rTHA
      (n = 165) and rTKA (n = 87) from March 2013 to December 2016. Outcomes include
      length of stay (LOS), 31-day complication rates for thrombotic events and
      infection and 31-day readmission rates (RR). Results: Overall rates of IH were
      11.7%; with cohort analysis demonstrating rates of 13.2%, 11.2%, 8.3% and 3.9% in
      THA, TKA, rTHA and rTKA respectively. Patients with body mass index (BMI)<29
      kg/m2 and undergoing THA were at risk of IH. For all TJA, no difference was
      observed in 31-day complications (1.6% vs. 2.8%, p = 0.19), 31-day RR (3.3% vs.
      4.5%, p = 0.50) or LOS (4.6 +/- 2.9 vs. 5.1 +/- 4.5, p = 0.11). IH was associated
      with higher RR for haematoma in TKA (2.9% vs. 0.4%, p = 0.021) and higher deep
      infection rates in rTHA (20% vs 0%, p = 0.006). Conclusion: Our study
      demonstrates a 3.9% to 13.2% rate of IH in TJA, with lower BMI, THA and primary
      cases as risk factors. We recommend protective steps are taken to maintain
      patient normothermia in these groups.

PMID- 29379255
TI  - Current trends in small molecule discovery targeting key cellular signaling
      events towards the combined management of diabetes and obesity.
AB  - Non-insulin dependent diabetes mellitus, also known as Type 2 diabetes is a
      polygenic disorder leading to abnormalities in the carbohydrate and lipid
      metabolism. The major contributors in the pathophysiology of type 2 diabetes
      (T2D) include resistance to insulin action, beta cell dysfunction, an abnormality
      in glucose metabolism and storage, visceral obesity and to some extent
      inflammation and oxidative stress. Insulin resistance, along with a defect in
      insulin secretion by the pancreatic beta cells is instrumental towards
      progression to hyperglycemia. Increased incidence of obesity is also a major
      contributing factor in the escalating rates of type 2 diabetes. Drug discovery
      efforts are therefore crucially dependent on identifying individual molecular
      targets and validating their relevance to human disease. The current review
      discusses bioactive compounds from medicinal plants offering enhanced therapeutic
      potential for the combined patho-physiology of diabetes and obesity. We have
      demonstrated that 3beta-taraxerol a pentacyclic triterpenoid (14-taraxeren-3-ol)
      isolated from the ethyl acetate extract of Mangifera indica, chlorogenic acid
      isolated from the methanol extract of Cichorium intybus, methyl tetracosanoate
      from the methanol extract of Costus pictus and vitalboside A derived from
      methanolic extract of Syzygium cumini exhibited significant effects on insulin
      stimulated glucose uptake causing insulin sensitizing effects on 3T3L1 adipocytes
      (an in vitro model mimicking adipocytes). Whereas, (3beta)-stigmast-5-en-3-ol
      isolated from Adathoda vasica and Aloe emodin isolated from Cassia fistula showed
      significant insulin mimetic effects favoring glucose uptake in L6 myotubes (an in
      vitro model mimicking skeletal muscle cells). These extracts and molecules showed
      glucose uptake through activation of PI3K, an important insulin signaling
      intermediate. Interestingly, cinnamic acid isolated from the hydro-alcohol
      extract of Cinnamomum cassia was found to activate glucose transport in L6
      myotubes through the involvement of GLUT4 via the PI3K-independent pathway.
      However, the activation of glucose storage was effective in the presence of 3beta
      taraxerol and aloe emodin though inhibition of GSK3beta activity. Therefore, the
      mechanism of improvement of glucose and lipid metabolism exhibited by the small
      molecules isolated from our lab is discussed. However, Obesity is a major risk
      factor for type-2 diabetes leading to destruction of insulin receptors causing
      insulin resistance. Identification of compounds with dual activity (anti-diabetic
      and antiadipogenic activity) is of current interest. The protein tyrosine
      phosphatase 1B (PTP1B) is an important negative regulator of the insulin and
      leptin-signaling pathway is of significance in target definition and discovery.

PMID- 29379256
TI  - Antifreeze proteins.
AB  - The antifreeze protein (AFP) activity is explained using two models. The first
      model is using ice binding and the second is using antiice structuralization of
      water molecules. The description of AFP function using anti-ice structuralization
      of water molecules is less explored. Therefore, it is of interest to explain AFP
      function using this model. Protein folding is often described using models where
      hydrophobic residues move away from water getting buried and hydrophilic residues
      are exposed to the surface. Thus, the 3D Gauss function stretched on the protein
      molecule describes the hydrophobicity distribution in a protein molecule. Small
      antifreeze proteins (less than 150 residues) are often represented by structures
      with hydrophobic core. Large antifreeze proteins (above 200 residues) contain
      solenoid (modular repeats). The hydrophobic field of solenoid show different
      distribution with linear propagation of the bands of different hydrophobicity
      level having high and low hydrophobicity that is propagated parallel to the long
      axis of solenoid. This specific ordering of hydrophobicity implies water
      molecules ordering different from ice. We illustrate this phenomenon using two
      antifreeze proteins to describe the hypothesis.

PMID- 29379257
TI  - Current trends for customized biomedical software tools.
AB  - In the past, biomedical scientists were solely dependent on expensive commercial
      software packages for various applications. However, the advent of user-friendly
      programming languages and open source platforms has revolutionized the
      development of simple and efficient customized software tools for solving
      specific biomedical problems. Many of these tools are designed and developed by
      biomedical scientists independently or with the support of computer experts and
      often made freely available for the benefit of scientific community. The current
      trends for customized biomedical software tools are highlighted in this short
      review.

PMID- 29379258
TI  - Current views and challenges on clinical cholera.
AB  - Cholera, an acute diarrheal infection has become a major global threat. Vibrio
      cholerae the causative agent of cholera has been responsible for six previous
      pandemics since 1817 that spanned four continents and Australia with the seventh
      pandemic ongoing since 1961. Two serogroups of V. cholerae O1 and O139 have the
      ability to secrete the enterotoxin with potential to cause epidemics. The prior
      six pandemics were caused by the classical biotype of the O1 serogroup. However,
      the emergence of the El Tor biotype and subsequent variants of El Tor with
      classical traits are the main isolates in the seventh pandemic. Cholera outbreaks
      have increased among vulnerable communities affected by war, earthquakes,
      conflicts and famines. Annually, 2.9 million cases of cholera occur globally in
      69 endemic countries with 95,000 deaths. Early detection followed by prompt fluid
      and electrolyte replacement can reduce the case fatality ratio significantly.
      Improvements in water systems, sanitation and hygiene have effectively eliminated
      the transmission of cholera in high-income countries and reduced transmission in
      some developing nations. However, an estimated 1.8 billion are still at risk for
      cholera due to lack of potable water, inadequate sanitation and hygiene.
      Interventions focusing on hygiene in conjunction with proper disposal and
      treatment of sewage and provision of safe drinking water are likely to be
      effective in preventing the recurrence of cholera. Lastly, the use of current
      oral vaccines in endemic settings in combination with WASH interventions may be
      an effective approach to prevent and reduce the spread of cholera infection.

PMID- 29379259
TI  - Artificial Intelligence and Virology - quo vadis.
AB  - Artificial Intelligence (AI), robotics, co-robotics (cobots), quantum computers
      (QC), include surges of scientific endeavor to produce machines (mechanical and
      software) among numerous types and constructions that are accelerating progress
      to defeat infectious diseases. There is a plethora of additional applications and
      uses of these methodologies and technologies for the understanding of biomedicine
      through bioinformation discovery. Therefore, we briefly outline the use of such
      techniques in virology.

PMID- 29379260
TI  - Telenursing: Bioinformation Cornerstone in Healthcare for the 21st Century.
AB  - Bioinformation is at the very core of 21st-century healthcare. Telehealth
      consists of the range of healthcare-related services delivered through
      bioinformation-aided telecommunications across health-related disciplines,
      including nursing. Whereas it is clear that bedside patient-centered nursing can
      never be replaced, recent developments in bioinformation-aided telenursing will
      undoubtedly contribute to improving healthcare effectiveness and efficacy.
      Current trends show that as telenursing becomes increasingly timely and critical,
      healthcare professionals adopt new and improved evidence-based practices as a
      standard for patient care worldwide.

PMID- 29379261
TI  - Recent trends in antimicrobial peptide prediction using machine learning
      techniques.
AB  - The importance to develop effective alternatives to known antibiotics due to
      increased microbial resistance is gaining momentum in recent years. Therefore, it
      is of interest to predict, design and computationally model Antimicrobial
      Peptides (AMPs). AMPs are oligopeptides with varying size (from 5 to over100
      residues) having key role in innate immunity. Thus, the potential exploitation of
      AMPs as novel therapeutic agents is evident. They act by causing cell death
      either by disrupting the microbial membrane by inhibiting extracellular polymer
      synthesis or by altering intra cellular polymer functions. AMPs have broad
      spectrum activity and act as first line of defense against all types of
      microorganisms including viruses, bacteria, parasites, fungi and as well as
      cancer (uncontrolled celldivision) progression. Large-scale identification and
      extraction of AMPs is often non-trivial, expensive and time consuming. Hence,
      there is a need to develop models to predict AMPs as therapeutics. We document
      recent trends and advancement in the prediction of AMP.

PMID- 29379262
TI  - Computer aided epitope design as a peptide vaccine component against Lassa virus.
AB  - Lassa virus (LASV) is an arena virus causing hemorrhagic fever and it is endemic
      in several regions of West Africa. The disease-causing virus records high
      mortality rate in endemic regions due to lack of appropriate treatment and
      prevention strategies. Therefore, it is of interest to design and develop viable
      vaccine components against the virus. We used the Lassa virus envelope glyco
      proteins as a vaccine target to identify linear peptides as potential epitopes
      with immunogenic properties by computer aided epitope prediction tools. We report
      a T-cell epitope 'LLGTFTWTL' and a B-cell epitope 'AELKCFGNTAVAKCNE' with
      predicted potential immunogenicity for further in vivo and in vitro
      consideration.

PMID- 29379263
TI  - Characterization of a hypothetical protein YVRE from Bacillus subtilis indicates
      its key role as glucono-lactonase in pentose phosphate pathway and glucose
      metabolism.
AB  - Hypothetical proteins are functionally uncharacterized proteins with assigned
      function using sequence annotation tools. Almost half of the coding regions of
      several genomes are hypothetical proteins. Therefore, it is of our interest to
      characterize a hypothetical protein YVRE from the model system Bacillus subtilis
      using known data. YVRE is assigned the function as a glucono-lactonase using
      prediction and phylogenetic analysis. A molecular dynamics simulated homology
      model of YVRE (with calcium) using human senescence marker protein 30 /SMP30 (PDB
      ID: 3G4E) as template is reported for functional inference. It is observed that
      the protein possesses bivalent metal binding domain. Molecular docking studies
      with the substrate glucono-delta-lactone show YVRE binding with the substrate.
      This data was further validated using cloning and sub-cloning in pUC57 and
      pET22b+ respectively, followed by expression and purification using nickel
      affinity chromatography. The activity of YVRE using the substrate glucono-delta
      lactone was calculated. The results show the function of YVRE as a
      gluconolactonase, with higher preference to zinc than calcium or magnesium. Thus,
      YVRE is shown to play key role in three metabolic pathways namely, pentose
      phosphate pathway, ascorbate and aldarate metabolism, and caprolactam
      degradation.

PMID- 29379264
TI  - Population Based Image Imputation.
AB  - We present an algorithm for creating high resolution anatomically plausible
      images consistent with acquired clinical brain MRI scans with large inter-slice
      spacing. Although large databases of clinical images contain a wealth of
      information, medical acquisition constraints result in sparse scans that miss
      much of the anatomy. These characteristics often render computational analysis
      impractical as standard processing algorithms tend to fail when applied to such
      images. Highly specialized or application-specific algorithms that explicitly
      handle sparse slice spacing do not generalize well across problem domains. In
      contrast, our goal is to enable application of existing algorithms that were
      originally developed for high resolution research scans to significantly
      undersampled scans. We introduce a model that captures fine-scale anatomical
      similarity across subjects in clinical image collections and use it to fill in
      the missing data in scans with large slice spacing. Our experimental results
      demonstrate that the proposed method outperforms current upsampling methods and
      promises to facilitate subsequent analysis not previously possible with scans of
      this quality.

PMID- 29379265
TI  - DNA Computing Systems Activated by Electrochemically-triggered DNA Release from a
      Polymer-brush-modified Electrode Array.
AB  - An array of four independently wired indium tin oxide (ITO) electrodes was used
      for electrochemically stimulated DNA release and activation of DNA-based
      Identity, AND and XOR logic gates. Single-stranded DNA molecules were loaded on
      the mixed poly(N,N-di-methylaminoethyl methacrylate) (PDMAEMA)/poly-(methacrylic
      acid) (PMAA) brush covalently attached to the ITO electrodes. The DNA deposition
      was performed at pH 5.0 when the polymer brush is positively charged due to
      protonation of tertiary amino groups in PDMAE-MA, thus resulting in electrostatic
      attraction of the negatively charged DNA. By applying electrolysis at -1.0 V(vs.
      Ag/AgCl reference) electrochemical oxygen reduction resulted in the consumption
      of hydrogen ions and local pH increase near the electrode surface. The process
      resulted in recharging the polymer brush to the negative state due to
      dissociation of carboxylic groups of PMAA, thus repulsing the negatively charged
      DNA and releasing it from the electrode surface. The DNA release was performed in
      various combinations from different electrodes in the array assembly. The
      released DNA operated as input signals for activation of the Boolean logic gates.
      The developed system represents a step forward in DNA computing, combining for
      the first time DNA chemical processes with electronic input signals.

PMID- 29379266
TI  - Surgically induced astigmatism after phacoemulsification by temporal clear
      corneal and superior clear corneal approach: a comparison.
AB  - Introduction: Cataract surgery has undergone various advances since it was
      evolved from ancient couching to the modern phacoemulsification cataract surgery.
      Surgically induced astigmatism (SIA) remains one of the most common
      complications. The introduction of sutureless clear corneal incision has gained
      increasing popularity worldwide because it offers several advantages over the
      traditional sutured limbal incision and scleral tunnel. A clear corneal incision
      has the benefit of being bloodless and having an easy approach, but SIA is still
      a concern. Purpose: In this study, we evaluated the SIA in clear corneal
      incisions with temporal approach and superior approach phacoemulsification.
      Comparisons between the two incisions were done using keratometric readings of
      preoperative and postoperative refractive status. Methodology: It was a hospital
      based prospective interventional comparative randomized control trial of 261
      patients conducted in a rural-based tertiary care center from September 2012 to
      August 2014. The visual acuity and detailed anterior segment and posterior
      segment examinations were done and the cataract was graded according to Lens
      Opacification Classification System II. Patients were divided for
      phacoemulsification into two groups, group A and group B, who underwent temporal
      and superior clear corneal approach, respectively. The patients were followed up
      on day 1, 7, 30, and 90 postoperatively. The parameters recorded were uncorrected
      visual acuity, best-corrected visual acuity, slit lamp examination, and
      keratometry. The mean difference of SIA between 30th and 90th day was
      statistically evaluated using paired t-test, and all the analyses were performed
      using SPSS 18.0 (SPSS Inc.) software. Results: The mean postoperative SIA in
      group A was 0.998 D on the 30th day, which reduced to 0.768 D after 90 days, and
      in group B the SIA after 30 days was 1.651 D, whereas it reduced to 1.293 D after
      90 days. Conclusion: Temporal clear corneal incision is evidently better than
      superior clear corneal incision as far as SIA is concerned.

PMID- 29379267
TI  - Goldmann tonometry tear film error and partial correction with a shaped
      applanation surface.
AB  - Purpose: The aim of the study was to quantify the isolated tear film adhesion
      error in a Goldmann applanation tonometer (GAT) prism and in a correcting
      applanation tonometry surface (CATS) prism. Methods: The separation force of a
      tonometer prism adhered by a tear film to a simulated cornea was measured to
      quantify an isolated tear film adhesion force. Acrylic hemispheres (7.8 mm
      radius) used as corneas were lathed over the apical 3.06 mm diameter to simulate
      full applanation contact with the prism surface for both GAT and CATS prisms.
      Tear film separation measurements were completed with both an artificial tear and
      fluorescein solutions as a fluid bridge. The applanation mire thicknesses were
      measured and correlated with the tear film separation measurements. Human cadaver
      eyes were used to validate simulated cornea tear film separation measurement
      differences between the GAT and CATS prisms. Results: The CATS prism tear film
      adhesion error (2.74+/-0.21 mmHg) was significantly less than the GAT prism
      (4.57+/-0.18 mmHg, p<0.001). Tear film adhesion error was independent of
      applanation mire thickness (R2=0.09, p=0.04). Fluorescein produces more tear film
      error than artificial tears (+0.51+/-0.04 mmHg; p<0.001). Cadaver eye validation
      indicated the CATS prism's tear film adhesion error (1.40+/-0.51 mmHg) was
      significantly less than that of the GAT prism (3.30+/-0.38 mmHg; p=0.002).
      Conclusion: Measured GAT tear film adhesion error is more than previously
      predicted. A CATS prism significantly reduced tear film adhesion error by41%.
      Fluorescein solution increases the tear film adhesion compared to artificial
      tears, while mire thickness has a negligible effect.

PMID- 29379268
TI  - Glaucoma related retinal oximetry: a technology update.
AB  - There are two long-standing theories about the pathogenesis of glaucoma -
      barotrauma and the effect of vascular hypoxia. Currently, it is still unknown
      whether diminished blood flow is the cause or result of glaucomatous atrophy of
      ganglion cells and the optic nerve. Though many other imaging techniques used to
      directly assess ocular blood flow have been well studied, they are limited by
      their inability to directly assess metabolism in the ocular tissues or measure
      the oxygen carrying capacity in the vessels. Retinal oximetry is a relatively
      novel, noninvasive imaging technique that reliably measures oxygen saturation
      levels in the retinal vessels, offering surrogate markers for the metabolic
      demands of the eye. The clinical significance of these measurements has not been
      well established. Thus, this review gives an overview of ocular imaging and
      current retinal oximetry techniques, while contextualizing the important oximetry
      studies that have investigated the vascular theory behind glaucoma.

PMID- 29379269
TI  - Physiologic anisocoria under various lighting conditions.
AB  - Purpose: To evaluate the measurement of anisocoria in a group of ocular healthy
      subjects using a standardized protocol in scotopic, mesopic, and photopic
      lighting conditions, and determine the optimal threshold of difference in pupil
      diameter in determining physiologic anisocoria. Methods: Right and left pupil
      diameters of 126 ocular healthy subjects with a mean age 30.5+/-7.8 years (40
      males and 86 females) were measured sequentially under photopic conditions using
      a monocular infrared pupillometer. A sub-group of 51 individuals had right and
      left pupil measurements performed under three additional lighting conditions,
      allowing for a 2-minute recovery between measurements. A white light emitting
      diode (LED) in the eyecup of the pupillometer produced three controlled light
      settings: scotopic (0 lux), low mesopic (0.3 lux), and high mesopic (3 lux). The
      criterion for anisocoria was defined as >=0.4 mm difference in pupil diameter
      between the eyes. Results: In the 126 subjects tested, 23.8% (n=30) exhibited
      anisocoria in photopic conditions. In the sub-group measured under three
      additional light settings, 43.1% (n=22) exhibited anisocoria in scotopic
      conditions, 43.1% (n=22) in low mesopic conditions, and 47.1% (n=24) in high
      mesopic conditions. Approximately 73% of subjects exhibited anisocoria in at
      least one light setting, while only approximately 8% had anisocoria in every
      light setting. When the criterion for anisocoria was shifted to >=0.2 mm or >=0.6
      mm, the prevalence of anisocoria shifted significantly. Using a higher cutoff of
      >=0.6 mm effectively reduced the number of healthy individuals who exhibit
      anisocoria in every light setting to almost zero. Conclusion: Based on our data,
      anisocoria is more prevalent under varied lighting conditions. To ensure the
      anisocoria is due to physiologic reasons, one should ensure that it is present
      under all lighting conditions to avoid excessive false positives.

PMID- 29379270
TI  - Satisfaction and convenience of using terpenoid-impregnated eyelid wipes and
      teaching method in people without blepharitis.
AB  - Purpose: Demodex infestations cause blepharitis and are difficult to treat.
      Recently, a new type of eyelid wipes with terpenoids has been found effective. We
      aim to evaluate patient satisfaction after short-term use and compare two
      teaching modalities on the techniques of use. Patients and methods: Eligible
      participants were taught to use eyelid wipes (Cliradex(r)) by either live or
      online video demonstration based on random allocation. Participants used the
      wipes twice daily for a week. All participants had prior evaluation of
      socioeconomic status, dry eye symptoms, and meibomian gland features. After 1
      week, competence of use was assessed by participants showing their technique to
      the investigator, and a questionnaire on comfort, ease, and convenience of use
      was administered. Higher scores indicate greater satisfaction, and these levels
      are compared among the two teaching modalities using chi square. Results: A total
      of 50 participants were recruited, with a mean age of 42+/-16 years, and 88% of
      the participants were females. Overall, median comfort level was 4.0 (range: 1
      6), ease level was 5.0 (3-6), and convenience level was 5.0 (2-6). Median
      stinging was 2.0 (1-4), which corresponded to some but mild stinging. The median
      competence level was 4.0 (2-4), which corresponded to excellent competence. These
      satisfactory levels (ease, comfort, and convenience) experienced were not
      significantly associated with different socioeconomic indicators, that is,
      housing type, income, highest education level, and were not different between
      teaching methods (p>0.05). Conclusion: Short-term use of Cliradex eyelid wipes
      seems to be acceptable to most people. The teaching instructions before using
      these wipes were equally effective - whether live or online video demonstration
      was used.

PMID- 29379271
TI  - Sinomenine reduces neuronal cell apoptosis in mice after traumatic brain injury
      via its effect on mitochondrial pathway.
AB  - Background: Sinomenine (SIN) has been shown to have protective effects against
      brain damage following traumatic brain injury (TBI). However, the mechanisms and
      its role in these effects remain unclear. This study was conducted to investigate
      the potential mechanisms of the protective effects of SIN. Methods: The weight
      drop model of TBI in Institute of Cancer Research (ICR) mice were treated with
      SIN or a vehicle via intraperitoneal administration 30 min after TBI. All mice
      were euthanized 24 h after TBI and after neurological scoring, a series of tests
      were performed, including brain water content and neuronal cell death in the
      cerebral cortex. Results: The level of cytochrome c (Cyt c), malondialdehyde
      (MDA), glutathione peroxidase (GPx) and superoxide dismutase 1 (SOD) were
      restored to some degree following the SIN treatment. The SIN treatment
      significantly decreased caspase-3 expression and reduced the number of positive
      cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) assay and improved the survival of neuronal cells. Additionally, the
      pretreatment levels of MDA were restored, while Bax translocation to mitochondria
      and Cyt c release into the cytosol were reduced by the SIN treatment. Conclusion:
      SIN protected neuronal cells by protecting them against apoptosis via mechanisms
      that involve the mitochondria following TBI.

PMID- 29379272
TI  - Does knowledge on diabetes management influence glycemic control? A nationwide
      study in patients with type 1 diabetes in Brazil.
AB  - Objective: The purpose of this study is to establish demographic and clinical
      data associated with the knowledge on diabetes management and its influence on
      glycemic control in patients with type 1 diabetes. Methods: This was a
      retrospective, observational, multicenter study conducted with 1,760 patients
      between August 2011 and August 2014 in 10 cities of Brazil. Results: Overall,
      1,190 (67.6%) patients knew what glycated hemoglobin (HbA1c) means. These
      patients were older, had longer disease duration, longer follow-up in each
      center, reported lower frequency of self-reported hypoglycemia, and were more
      frequently Caucasians and at glycemic goal. Multivariate analysis showed that
      knowledge on what HbA1c means was related to more years of school attendance,
      self-reported ethnicity (Caucasians), severe hypoglycemia, economic status,
      follow-up time in each center, and participation on diabetes educational
      programs. Good glycemic control was related to older age, more years of school
      attendance, higher frequency of daily self-monitoring of blood glucose, higher
      adherence to diet, and knowledge on what HbA1c means. Conclusion: Patients with a
      knowledge on what HbA1c means had a better chance of reaching an adequate
      glycemic control that was not found in the majority of our patients. Diabetes
      care teams should rethink the approaches to patients and change them to more
      proactive schedules, reinforcing education, patients' skills, and empowerment to
      have positive attitudes toward reaching and maintaining a better glycemic
      control. Finally, the glucocentric approach to diabetes management should be
      changed to actions that include patients' psychosocial aspects aiming to reduce
      the stress of living with diabetes, improving glycemic control, and avoiding
      adverse outcomes.

PMID- 29379273
TI  - Quantifying the treatment goals of people recently diagnosed with schizophrenia
      using best-worst scaling.
AB  - Objective: This study seeks to quantify the treatment goals of people recently
      diagnosed with schizophrenia and explore their impact on treatment plan. Methods:
      People aged 18-35 years with a confirmed diagnosis of schizophrenia within the
      past 5 years were surveyed in the UK, Germany, and Italy. Treatment goals were
      assessed via a validated best-worst scaling instrument, where participants
      evaluated subsets of 13 possible treatment goals identified using a balanced
      incomplete block design. Participants identified the most and least important
      goals within each task. Data were also collected on current treatment and
      preference for daily oral versus long-acting injectable (LAI) treatment.
      Hierarchical Bayes was used to identify preference weights for the goals, and
      latent class analysis was used to identify segments of people with similar goals.
      The segments were compared with the current treatment and preference for oral
      versus LAI treatment. Results: Across 100 participants, the average age was 26
      years, 75% were male and 50% were diagnosed within 2 years ago. Overall,
      preferences were most favorable for reduced disease symptoms, think clearly,
      reduced hospitalizations, reduced anxiety, and take care of self. A total of 61%
      preferred oral medication and 39% LAI. Two groups were identified with different
      treatment goals; 50% of participants emphasized clinical goals, including reduced
      disease symptoms (preference weight =19.7%), reduced hospitalizations (15.5%),
      and reduced anxiety (10.5%). The other 50% emphasized functional goals, including
      improved relationships with family/friends (11.4%), increased interest in work
      (10.6%), experiencing a fuller range of emotions (8.4%), and ability to socialize
      (7.5%). Those emphasizing functional goals were more likely to be on LAI (44%
      versus 26%; p=0.059) and preferred LAI (46% versus 32%; p=0.151). Conclusions:
      People with recent-onset schizophrenia may focus more on clinical goals or
      functional goals, a discussion of which may help facilitate patient engagement.

PMID- 29379274
TI  - Correlates of preferences for autonomy in long-term care: results of a population
      based survey among older individuals in Germany.
AB  - Purpose: Thus far, there is little evidence concerning the factors associated
      with preferences for autonomy in long-term care. Therefore, the aim of the
      present study was to investigate the correlates of preferences for autonomy in
      long-term care among older individuals in Germany. Methods: Data were gathered
      from a population-based survey of the German population aged >=65 years in 2015
      (N=1,006). Results: Multiple logistic regressions revealed that preferences for
      freedom of choice for foods were positively associated with living with partner
      or spouse (OR: 1.5 [1.0-2.2]), being born in Germany (OR: 1.9 [1.1-3.3]), and
      lower self-rated health (OR: 1.3 [1.1-1.6]). Preferences for freedom in choosing
      bedtime and sleep duration were positively associated with lower age (OR: 1.1
      [1.0-1.1]) and having children (OR: 2.2 [1.0-4.9]). Preferences for customized
      living space were positively associated with being female (OR: 2.5 [1.4-4.5]) and
      being born in Germany (OR: 3.7 [1.9-7.1]). Neither preferences for decent and
      sanitary housing nor preferences for shared decision-making were associated with
      any of the independent variables. Conclusion: Various independent variables were
      associated with preferences for autonomy in long-term care. This suggests that
      preferences for care-related autonomy are complex. Knowing these might help
      refine long-term care health services.

PMID- 29379275
TI  - Real-life experience of quality of life, treatment satisfaction, and adherence in
      patients receiving oral anticoagulants for atrial fibrillation.
AB  - Introduction: Direct oral anticoagulants (DOACs) have shown noninferiority to
      vitamin K antagonists (VKA) in stroke prevention in patients with atrial
      fibrillation. DOAC treatment may be less demanding than VKA, improving quality of
      life. To date, there have been no studies of the real-life experience of
      outpatients receiving anticoagulation therapy for atrial fibrillation in France.
      Methods: An observational descriptive real-life epidemiological study used three
      validated questionnaires (EQ-5D, PACT-Q2, and MMAS-8 French Translation) to
      assess quality of life, treatment satisfaction, and adherence, respectively, in
      200 patients managed on an outpatient basis for atrial fibrillation who were
      receiving anticoagulation therapy by VKA or DOAC for at least 3 months. Patients
      were distributed between four groups: primary VKA (P-VKA), switch from VKA to
      DOAC (S-DOAC), primary DOAC (P-DOAC), and switch from DOAC to VKA (S-VKA).
      Results: Two hundred patients responded to the questionnaires: 89, 50, 52, and 9
      in the P-VKA, S-DOAC, P-DOAC and S-VKA groups, respectively. Only the first three
      groups were compared statistically, because of the small size of the S-VKA group.
      Quality of life and satisfaction were good in all three groups, with no
      significant difference in quality of life but significantly greater satisfaction
      with respect to the "convenience" and "satisfaction" dimensions for DOACs (S-DOAC
      and P-DOAC groups versus P-VKA group; p<0.001, for both dimensions). Adherence
      did not significantly differ between groups. Conclusion: The experience of
      patients under oral anticoagulation therapy for atrial fibrillation managed on an
      outpatient basis was good, with comparable quality of life under DOACs and VKA,
      and significantly greater satisfaction under DOACs, without impact on adherence.
      Taking account of patient preference in "shared decision-making" for the choice
      of type of anticoagulant could improve the patients' experience of treatment.

PMID- 29379276
TI  - Psychological, interpersonal, and clinical factors predicting time spent on
      physical activity among Mexican patients with hypertension.
AB  - Background: It is widely known that physical activity is the key to the optimal
      management and clinical control of hypertension. Purpose: This research was
      conducted to identify factors that can predict the time spent on physical
      activity among Mexican adults with hypertension. Methods: This cross-sectional
      study was conducted among 182 Mexican patients with hypertension, who completed a
      set of self-administered questionnaires related to personality, social support,
      and medical adherence and health care behaviors, body mass index, and time since
      the disease diagnosis. Several path analyses were performed in order to test the
      predictors of the study behavior. Results: Lower tolerance to frustration, more
      tolerance to ambiguity, more effective social support, and less time since the
      disease diagnosis predicted more time spent on physical activity, accounting for
      13.3% of the total variance. The final model shows a good fit to the sample data
      (pBS =0.235, chi2/gl =1.519, Joreskog and Sorbom's Goodness of Fit Index =0.987,
      adjusted modality =0.962, Bollen's Incremental Fit Index =0.981, Bentler-Bonett
      Normed Fit Index =0.946, standardized root mean square residual =0.053).
      Conclusion: The performance of physical activity in patients with hypertension
      depends on a complex set of interactions between personal, interpersonal, and
      clinical variables. Understanding how these factors interact might enhance the
      design of interdisciplinary intervention programs so that quality of life of
      patients with hypertension improves and they might be able to manage and control
      their disease well.

PMID- 29379277
TI  - Sources and directions of social support and life satisfaction among solitary
      Chinese older adults in Hong Kong: the mediating role of sense of loneliness.
AB  - Based on survey data collected from 151 community-dwelling solitary Chinese older
      adults in Hong Kong, the present study used path analysis to examine the
      mediating role of sense of loneliness in the relationship between different
      sources and directions of social support and life satisfaction. The results
      showed that sense of loneliness mediated the effects of support from families,
      friends, and support for others on life satisfaction. In addition, a formal
      source of social support was not associated with life satisfaction among solitary
      older adults, although those with a more secure financial status had greater
      overall life satisfaction. These findings highlight the importance of enhancing
      awareness among social and health care service providers about the negative
      effects of insufficient social support on older adults' sense of loneliness and
      life satisfaction. Family and friendship networks should be expanded for solitary
      older adults.

PMID- 29379278
TI  - The effects of injecting intra-articular platelet-rich plasma or prolotherapy on
      pain score and function in knee osteoarthritis.
AB  - Introduction: Osteoarthritis (OA) is a chronic joint disease that usually occurs
      in older people and leads to pain and disabilities. OA treatment ranges from drug
      therapy to surgery. Drug and rehabilitation therapy are preferred over surgery,
      and, especially, there is a tendency toward compounds causing regenerative
      changes in the knee joint. In the present study, the effects of platelet-rich
      plasma (PRP) injection and prolotherapy (PRL) were examined on the level of pain
      and function of the knee joint in patients with OA. Methodology: After fulfilling
      the inclusion criteria and signing the informed consent form, 42 patients with
      knee OA were scheduled for intra-articular injection in the present randomized,
      double-blind, clinical trial. Following admission to the operating pain room, the
      condition of the patient's knee was evaluated first via the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC) and, then, ultrasound-guided
      knee injection was done. Accordingly, patients in the PRP therapy group received
      7 mL PRP solution and those in the PRL group received 7 mL 25% dextrose. Using
      the WOMAC, levels of pain and knee function were evaluated and recorded for each
      patient immediately prior to the first injection as well as at 1 month
      (immediately prior to the second injection), 2 months (a month after the second
      injection), and 6 months later. Data collected were analyzed using the SPSS v.20.
      Results: During the first and second months, a rapid decrease in the overall
      WOMAC score was observed in both groups. The overall WOMAC score increased at the
      sixth month, but was lower than the overall WOMAC score in the first month.
      Statistical analysis indicated that the overall WOMAC score significantly
      decreased in both groups of patients over 6 months. Conclusion: Results of the
      present study suggested a significant decrease in the overall WOMAC score of
      patients who undergo either PRP therapy or PRL. This positive change in the
      overall WOMAC score led to an improvement in the quality of life of patients with
      knee OA shortly after the first injection. PRP injection is more effective than
      PRL in the treatment of knee OA.

PMID- 29379279
TI  - Sex-related differences in effect-site concentration of remifentanil for
      preventing anesthetic emergence cough in elderly patients.
AB  - Purpose: Cough on anesthetic emergence should be prevented considering its
      dangerous complications. Target-controlled infusion (TCI) of remifentanil can
      reduce emergence cough effectively, and sex-related differences in effect-site
      concentration (Ce) of remifentanil have been evaluated in young patients. In this
      study, we determined the Ce of remifentanil for preventing emergence cough
      following extubation in male and female elderly patients and evaluated the sex
      related difference. Patients and methods: Twenty-three male and 22 female elderly
      patients aged between 60 and 75 years were enrolled. Anesthesia was maintained
      with sevoflurane and remifentanil TCI. The Ce of remifentanil for preventing
      emergence cough was determined for each sex using isotonic regression method with
      a bootstrapping approach, following Dixon's up-and-down method. Results: The Ce
      of remifentanil for preventing emergence cough in 50% (EC50) and 95% (EC95) of
      the population was significantly lower in females than in males. Isotonic
      regression revealed the EC50 (83% confidence interval [CI]) of remifentanil was
      1.67 (1.55-1.83) ng/mL in females and 2.60 (2.29-2.91) ng/mL in males. The EC95
      (95% CI) of remifentanil was 2.30 (2.02-2.62) ng/mL in females and 3.41 (3.27
      3.58) ng/mL in males. Dixon's up-and-down method indicated that the mean EC50 in
      females was lower than in males (1.56+/-0.26 ng/mL vs 2.56+/-0.37 ng/mL,
      P<0.001). Conclusion: The remifentanil requirement for preventing emergence cough
      was lower in female than in male elderly patients, indicative of sex-related
      differences in Ce of remifentanil. Sex should be considered when using
      remifentanil TCI for preventing emergence cough in elderly patients.

PMID- 29379280
TI  - Airway reactivity to mannitol is similarly increased in chronic cigarette and
      water pipe smokers.
AB  - Background: In contrast to cigarette smoking, the association between water pipe
      smoking and airway hyperresponsiveness remains widely unexplored. Methods: A
      bronchoprovocation challenge with mannitol was performed in young adults
      recruited at the University of Basel, Switzerland. Subjects were categorized as
      acute water pipe smokers (single episode of water pipe smoking, no or <0.5 pack
      years cigarette smoking); chronic water pipe smokers (weekly for >=4 weeks, no or
      <0.5 pack-years cigarette smoking); cigarette smokers (no water pipe smokers);
      and never-smokers (no cigarette or water pipe smokers). Primary outcomes were
      airway reactivity as measured by the response-to-dose ratio (RDR) and airway
      responsiveness measured by the provocation dose to cause a 15% fall in forced
      expiratory volume in 1s (FEV1; PD15). Results: Seventy-four subjects with a mean
      age of 22.5+/-2.5 years and FEV1 % predicted 90.1%+/-8.6% were included.
      Subgroups were matched in terms of age, gender, and spirometry results. RDR in
      chronic water pipe smokers and cigarette smokers was similar (0.013%/mg [0.010
      0.015] vs 0.023%/mg [0.011-0.051], respectively; p=0.12) but significantly higher
      than in never-smokers (0.007%/mg [0.005-0.010], p<0.01). Neither a history of
      asthma (p=0.88) nor a positive skin prick test (p=0.69) was associated with
      increased airway reactivity to the mannitol challenge test. PD15 differed
      significantly between cigarette smokers and never-smokers (155 mg [115-395] vs
      315 mg [155-475], respectively; p=0.04). Conclusion: Weekly water pipe smoking
      may increase airway reactivity to a similar extent as cigarette smoking.

PMID- 29379281
TI  - 2017 Global Initiative for Chronic Obstructive Lung Disease reclassifies half of
      COPD subjects to lower risk group.
AB  - Background: Unlike the 2014 guidelines, the 2017 Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) guidelines have removed lung function from the
      risk assessment algorithm of patients with COPD. The aim of this investigation
      was to analyze the proportion of subjects who would change to a lower risk group
      when applying GOLD2017 and determine if they exhibit different characteristics in
      terms of inflammation, symptoms and comorbidity compared to the subjects who
      would remain in a high-risk group. Subjects and methods: A total of 571 subjects
      with physician-diagnosed and spirometry-verified COPD were included in the
      present study. The data consisted of measurements of lung function, inflammatory
      markers, together with questionnaires that covered comorbidities, COPD symptoms
      and medication. Results: From group C, 53% of the subjects would be reclassified
      to the lower risk group A, and from group D, 47% of the subjects would be
      reclassified to the lower risk group B when using GOLD2017 instead of GOLD2014.
      Compared to the subjects who would remain in group D, those who would change to
      group B were more often men (56% vs 72%); of an older age, mean (SD), 71 (8)
      years vs 68 (7) years; had more primary care contact (54% vs 33%); had lower
      levels of blood neutrophils, geometrical mean (95% CI), 5.3 (5.0, 5.7) vs 4.6
      (4.3, 4.9); reported less anxiety/depression (20% vs 34%); experienced less
      asthma (29% vs 46%) and had fewer symptoms according to the COPD assessment test,
      16 (5) vs 21 (7). All p-values were <0.05. Conclusion: The removal of spirometry
      from risk assessment in GOLD2017 would lead to the reclassification of
      approximately half of the subjects in the risk groups C and D to the lower risk
      groups A and B. There are differences in age, gender, health care contacts,
      inflammation, comorbidity and symptom burden among those changing from group D to
      group B. The effects of reclassification and changes in eventual treatment for
      disease control and symptom burden need further investigation.

PMID- 29379282
TI  - Religious coping and religiosity in patients with COPD following pulmonary
      rehabilitation.
AB  - Background: Religious coping (RC) is defined as the use of behavioral and
      cognitive techniques in stressful life events in a multidimensional construct
      with positive and negative effects on outcomes, while religiosity is considered a
      use of individual beliefs, values, practices, and rituals related to faith. There
      is no evidence for the effects of pulmonary rehabilitation (PR) in RC and
      religiosity in patients with COPD. The aims of this study were 1) to compare RC
      and religiosity in patients with COPD following PR and 2) to investigate
      associations between changes in RC, religiosity and exercise capacity, quality of
      life (QoL), anxiety, depression, and dyspnea. Methods: Seventy-four patients were
      enrolled in this study including 38 patients in the PR group and 36 patients in
      the control group. PR protocol was composed of a 12-week (three sessions per
      week, 60 min per day) outpatient comprehensive program, and the control group was
      composed of patients in a waiting list for admission to PR program. RC,
      religiosity, exercise capacity, QoL, anxiety, depression, and dyspnea were
      measured before and after the study protocol. Results: Positive religious coping
      and organizational religious activities increased (p=0.01; p<0.001,
      respectively), while negative religious coping decreased (p=0.03) after 12 weeks
      in the PR group (p<0.001). Significant associations were observed between changes
      in RC, organizational religiosity with exercise capacity, and QoL following PR.
      No differences were found in the control group. Conclusion: PR improves RC and
      organizational religiosity in patients with COPD, and these improvements are
      related to increases in exercise capacity and QoL.

PMID- 29379283
TI  - Nano-graphene oxide composite for in vivo imaging.
AB  - Introduction: Positron emission tomography (PET) tracers has the potential to
      revolutionize cancer imaging and diagnosis. PET tracers offer non-invasive
      quantitative imaging in biotechnology and biomedical applications, but it
      requires radioisotopes as radioactive imaging tracers or radiopharmaceuticals.
      Method: This paper reports the synthesis of 18F-nGO-PEG by covalently
      functionalizing PEG with nano-graphene oxide, and its excellent stability in
      physiological solutions. Using a green synthesis route, nGO is then
      functionalized with a biocompatible PEG polymer to acquire high stability in PBS
      and DMEM. Results and discussion: The radiochemical safety of 18F-nGO-PEG was
      measured by a reactive oxygen species and cell viability test. The
      biodistribution of 18F-nGO-PEG could be observed easily by PET, which suggested
      the significantly high sensitivity tumor uptake of 18F-nGO-PEG and in a tumor
      bearing CT-26 mouse compared to the control. 18F-nGO-PEG was applied successfully
      as an efficient radiotracer or drug agent in vivo using PET imaging. This article
      is expected to assist many researchers in the fabrication of 18F-labeled graphene
      based bio-conjugates with high reproducibility for applications in the
      biomedicine field.

PMID- 29379284
TI  - Antimicrobial activity of silver nanoparticles encapsulated in poly-N
      isopropylacrylamide-based polymeric nanoparticles.
AB  - In this study, we analyzed the antimicrobial activities of poly-N
      isopropylacrylamide (pNIPAM)-based polymeric nanoparticles encapsulating silver
      nanoparticles (AgNPs). Three sizes of AgNP-encapsulating pNIPAM- and pNIPAM-NH2
      based polymeric nanoparticles were fabricated. Highly stable and uniformly
      distributed AgNPs were encapsulated within polymeric nanoparticles via in situ
      reduction of AgNO3 using NaBH4 as the reducing agent. The formation and
      distribution of AgNPs was confirmed by UV-visible spectroscopy, transmission
      electron microscopy, and inductively coupled plasma optical emission
      spectrometry, respectively. Both polymeric nanoparticles showed significant
      bacteriostatic activities against Gram-negative (Escherichia coli) and Gram
      positive (Staphylococcus aureus) bacteria depending on the nanoparticle size and
      amount of AgNO3 used during fabrication.

PMID- 29379285
TI  - Imaging and kinetics of the bimolecular complex formed by the tumor suppressor
      p53 with ubiquitin ligase COP1 as studied by atomic force microscopy and surface
      plasmon resonance.
AB  - p53 plays an important role in the safeguard of the genome but it is frequently
      downregulated mainly by E3 ubiquitin ligases among which COP1 plays an important
      role. The overexpression of COP1 has been reported to occur in several tumors and
      may be indicative of its overall oncogenic effect, which in turn might be
      originated by a direct interaction of COP1 with p53. Such an interaction may
      constitute a rewarding target for anticancer drug design strategies; therefore, a
      deeper understanding of its underlying molecular mechanism and kinetics is
      needed. The formation of a single p53-COP1 bimolecular complex was visualized by
      atomic force microscopy imaging on a mica substrate. The kinetic characterization
      of the complex, performed by atomic force spectroscopy and surface plasmon
      resonance, provided a KD value of ~10-8 M and a relative long lifetime in the
      order of minutes, both at the single-molecule level and in bulk solution. The
      surprisingly high affinity value and low dissociation rate of the p53-COP1
      bimolecular complex, which is even stronger than the p53-MDM2 complex, should be
      considered a benchmark for designing, development and optimization of suitable
      drugs able to antagonize the complex formation with the aim of preventing the
      inhibitory effect of COP1 on the p53 oncosuppressive function.

PMID- 29379286
TI  - The depressive-like behaviors of chronic unpredictable mild stress-treated mice,
      ameliorated by Tibetan medicine Zuotai: involvement in the hypothalamic-pituitary
      adrenal (HPA) axis pathway.
AB  - Background: Zuotai, a famous Tibetan medicinal mixture containing metacinnabar,
      is traditionally used for the purpose of tranquilizing minds and soothing nerves.
      However, it still lacks substantial experimental data for it to be approved for
      use. Aim: This study was designed to assess the effects of Zuotai on depressive
      like symptoms in a chronic unpredictable mild stress (CUMS) mouse model, and to
      explore its potential mechanism, particularly the hypothalamic-pituitary-adrenal
      (HPA) axis pathway. Materials and methods: First, Kunming mice were exposed to
      the CUMS procedure and simultaneously administered Zuotai or imipramine (positive
      control) by gavage continuously for 6 weeks. Then, depressive-like behaviors of
      mice in each group were tested with the sucrose preference test, forced swimming
      test, tail suspension test, and open field test. Meanwhile, the three key
      neuroendocrine hormones (corticotropin releasing hormone, adrenocorticotropic
      hormone and corticosterone) in HPA axis pathway, and the level of the emotion
      related monoamine neurotransmitters (5-hydroxytryptamine and norepinephrine) were
      measured using enzyme-linked immunosorbent assay. Furthermore, total mercury in
      the hypothalamus and hippocampus were determined using an automatic, direct
      mercury analyzer. Results: Zuotai or imipramine significantly increased the body
      weight and the sucrose preference ratio in sucrose preference test, and
      dramatically improved motor activity in forced swimming test, tail suspension
      test, and open field test in CUMS mice. Zuotai or imipramine remarkably decreased
      levels of corticotropin-releasing hormone, adrenocorticotropic hormone, and
      corticosterone in the HPA axis, and increased levels of 5-hydroxytryptamine and
      norepinephrine in the serum in CUMS mice. However, a small amount of mercury was
      deposited in the hypothalamus and hippocampus in Zuotai-treated mice, which may
      pose a potential risk to the central nervous system. Conclusion: Zuotai has a
      strong ability to ameliorate depressive-like behaviors in CUMS-treated mice
      through inhibition of the HPA axis and upregulation of monoamine
      neurotransmitters. These findings provide new insight into the pharmacological
      effect of Zuotai on depression.

PMID- 29379287
TI  - The association between hippocampal subfield volumes and education in cognitively
      normal older adults and amnestic mild cognitive impairment patients.
AB  - Objective: Previous research has indicated that there are potential associations
      between education and total hippocampal volume in the trajectory of Alzheimer's
      disease (AD). However, the correlation between education and hippocampal subfield
      volumes in the progression of AD has yet to be understood. This study examined
      the relationship between education, which is a standard proxy for cognitive
      reserve, and hippocampal subfield volumes in healthy and amnestic mild cognitive
      impairment (aMCI) groups. Subjects and methods: Thirty-eight subjects with aMCI
      and 39 healthy control subjects underwent 3 T magnetic resonance imaging, and
      hippocampal subfield volumes were measured by automated segmentation. Multiple
      linear regression analysis was used to determine the association between
      education and hippocampal subfield volumes. Results: Education had a significant
      negative correlation with the left parasubiculum, presubiculum, and subiculum
      volumes in the aMCI group. In addition, multiple subfield volumes including left
      parasubiculum, left/right presubiculum, left cornus ammonis (CA)3, and left CA4
      showed a significant correlation with the neuropsychological test scores in the
      control group and aMCI group. Conclusion: These findings contribute to a better
      understanding of the association between education, hippocampal subfield volumes,
      and amnestic cognitive functions in the early phase of AD.

PMID- 29379288
TI  - A meta-analysis of data associating DRD4 gene polymorphisms with schizophrenia.
AB  - To explore the association between DRD4 polymorphisms and schizophrenia risk, a
      meta-analysis was carried out with 41 case-control articles. Specifically, we
      included 28 articles (5,735 cases and 5,278 controls) that pertained to the 48 bp
      variable number tandem repeat (VNTR) polymorphism, nine articles (1,517 cases and
      1,746 controls) that corresponded to the 12 bp tandem repeat (TR), six articles
      (1,912 cases and 1,836 controls) that addressed the 120 bp TR, 10 articles (2,927
      cases and 2,938 controls) that entailed the -521 C>T polymorphism, six articles
      (1,735 cases and 1,724 controls) that pertained to the -616 C>G polymorphism, and
      four articles (1,191 cases and 1,215 controls) that involved the -376 C>T
      polymorphism. Pooled analysis, subgroup analysis, and sensitivity analysis were
      performed, and the data were visualized by means of forest and funnel plots.
      Results of pooled analysis indicated that the -521 CC variant (Pz=0.009, odds
      ratio [OR] =1.218, 95% confidence interval [CI] =1.050-1.413) and genotype L/L
      (ie, long allele) of the 120 bp TR were risk factors of schizophrenia (Pz=0.004,
      OR =1.275, 95% CI =1.081-1.504). The 48 bp VNTR, the 12 bp TR, the -616 C>G
      polymorphism, and the -376 C>T polymorphism were not associated with
      schizophrenia. Additional research is warranted to explore the association
      between polymorphisms of DRD4 and schizophrenia risk.

PMID- 29379289
TI  - The current status of culturally adapted mental health interventions: a practice
      focused review of meta-analyses.
AB  - In recent years, there has been a steadily increasing recognition of the need to
      improve the cultural competence of services and cultural adaptation of
      interventions so that every individual can benefit from evidence-based care.
      There have been attempts at culturally adapting evidence-based interventions for
      mental health problems, and a few meta-analyses have been published in this area.
      This is, however, a much debated subject. Furthermore, there is a lack of a
      comprehensive review of meta-analyses and literature reviews that provide
      guidance to policy makers and clinicians. This review summarizes the current meta
      analysis literature on culturally adapted interventions for mental health
      disorders to provide a succinct account of the current state of knowledge in this
      area, limitations, and guidance for the future research.

PMID- 29379290
TI  - Diagnostic challenges in multiple system atrophy.
AB  - Multiple system atrophy is a progressive neurodegenerative disorder that is
      characterized by autonomic failure, cerebellar ataxia and parkinsonism syndrome
      in various combinations. In spite of the presence of well-established clinical
      criteria for multiple system atrophy, ante-mortem diagnosis is difficult. In our
      case report, we present a 78-year-old female patient who presented with early
      progressive aphasia and severe autonomic dysfunction. Two years after appearance
      of the first symptoms, she fulfilled all the major criteria for probable multiple
      system atrophy with rapid progression. In addition, brain magnetic resonance
      imaging and fluorodeoxyglucose-positron emission tomography findings were more
      typical for progressive supranuclear palsy. Clinically differentiating multiple
      system atrophy from progressive supranuclear palsy and other similar
      neurodegenerative disorders may be challenging in all stages of the disease,
      especially with atypical disease presentation.

PMID- 29379291
TI  - Low level of knowledge regarding diagnosis and treatment among inpatients with
      schizophrenia in Shanghai.
AB  - Objective: The study was designed to measure the level of knowledge of the
      diagnosis of illness and its treatment among patients with schizophrenia in
      China, and to examine the association between the capacity to provide informed
      consent and participation in treatment. Participants and methods: A cross
      sectional study was conducted at three clinical inpatient sites in Shanghai,
      China, during 2015. Patients' knowledge of the illness, as well as the knowledge
      of the patients' families and psychiatrists, was determined. Logistic regression
      was used to determine the factors associated with patients' knowledge of
      schizophrenia. Results: Out of 109 enrolled schizophrenic inpatients (mean age
      42.46+/-1.29 years), 60.6% were aware of their diagnosis and 67.0% knew details
      of their treatment plan. The group with unimpaired capacity for giving informed
      consent had a greater knowledge of their diagnosis (chi2=5.002, p=0.038) and of
      their treatment plan (chi2=11.196, p<0.01) in comparison with patients who were
      regarded to be impaired. Using logistic regression analysis, it was found that
      patients' capacity to give informed consent to treatment was associated with the
      level of knowledge surrounding the diagnosis (odds ratio =3.230, p<0.05) and the
      level of knowledge of treatment (odds ratio =4.962, p<0.01). Conclusion: The
      level of knowledge reported by inpatients with schizophrenia was low with respect
      to the diagnosis of schizophrenia and of the treatment associated with this
      illness. An association between patients' capacities for giving informed consent
      and knowledge of their illness was confirmed in the present study. The results
      suggest that, in clinical practice, the informed consent process should be
      strengthened to protect the interests of patients with schizophrenia.

PMID- 29379292
TI  - Adherence to riluzole in patients with amyotrophic lateral sclerosis: an
      observational study.
AB  - Objective: Riluzole is the first drug approved to treat amyotrophic lateral
      sclerosis (ALS). Recently, an oral suspension (OS) of riluzole was made
      available. Thus, the aim of our study was to evaluate the adherence to 2
      formulations of riluzole in patients with ALS. Patients and methods: We enrolled
      45 consecutive patients with ALS. At disease diagnosis, riluzole was prescribed
      in 2 different formulations depending on the severity of dysphagia (27/45
      patients received tablets and 18/45 patients received OS). Side effects (SEs) and
      treatment adherence were investigated using a clinical questionnaire including
      the (c)Morisky 8-item Medication Adherence Questionnaire. Results: Gastroenteric
      complaints were the most frequent SEs (58% in the tablet group and 48% in the OS
      group), followed by those at the nervous system (29% and 40%, respectively). No
      serious SEs related to treatment were reported. The rate of adherence to riluzole
      was independent of the formulation of the drug and consistent with other
      medications assumed for comorbidities (p=0.004). In the tablet group, low
      adherence was caused by SEs in 55.6% and by dysphagia in 44.4% of patients. In
      the OS group, SEs caused low adherence in 75% of patients. Independently of the
      drug formulation, patients with high or medium adherence to riluzole had a higher
      progression rate (p=0.002 and p=0.009, respectively) and a shorter time to
      generalization (TTG; p=0.01), compared to those with low adherence. Conclusion:
      Gastroenteric symptoms were the most frequent SE related to tablet as well as OS.
      The rate of adherence was independent of the formulation of riluzole and the
      number of medications assumed for comorbidities, and it was consistent with the
      severity of the disease. The low adherence was caused by dysphagia and SEs in the
      tablet group, whereas it was caused prevalently by SEs in the OS group.

PMID- 29379294
TI  - Exploring the effect of chidamide on blastic plasmacytoid dendritic cell
      neoplasm: a case report and literature review.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive
      hematopoietic malignancy mainly affecting elderly patients. It is highly
      responsive to chemotherapy, but the median event-free survival is very short and
      has a high rate of relapse even after performing allogeneic stem cell
      transplantation; thus, the discovery of novel agents for the treatment of BPDCN
      is urgent. Chidamide is a new oral isotype-selective histone deacetylase
      inhibitor (HDACi). It is proved to exert a well-characterized anticancer property
      in a wide range of hematological malignancies, especially lymphoma. Here, we
      report a 41-year-old man who used oral chidamide 30 mg twice per week for
      maintenance therapy after receiving complete remission. For the first time in
      this field, we had explored the efficiency of chidamide in the treatment of BPDCN
      and tried to give more choices to the therapy of this disease.

PMID- 29379293
TI  - Efficacy and safety profile of paliperidone palmitate injections in the
      management of patients with schizophrenia: an evidence-based review.
AB  - The course of schizophrenia is characterized by multiple relapses, incomplete
      remission of symptoms, enduring cognitive deficits, and social and occupational
      functional impairments. Nonadherence to antipsychotic medication is a major
      determinant of this poor outcome. Long-acting injectable antipsychotics were
      developed specifically to address the nonadherence problem and are increasingly
      considered as an early treatment option, in an attempt to prevent accruing
      morbidity. This review focuses on paliperidone palmitate, the long-acting
      injectable (LAI) formulation of paliperidone. After considering the pharmacology
      of paliperidone palmitate, we review the randomized controlled trials, as well as
      pertinent observational, pragmatic studies for paliperidone once-monthly
      injections in schizophrenia. Finally, we review the recently introduced 3-monthly
      formulation of paliperidone palmitate. Taken together, the studies indicate that
      paliperidone palmitate (PP) has good efficacy compared with placebo and
      comparable with other antipsychotics including risperidone. The tolerability
      profile of PP is similar to that of risperidone, with the most important side
      effects being prolactin elevation, weight gain, and extrapyramidal symptoms.
      Advantages of PP include the extensive research database and clinical experience
      with paliperidone and its parent compound risperidone, the availability of
      different LAI formulations (once-monthly, 3-monthly, and perhaps even longer
      acting formulations in future), and the novel dose initiation procedure that
      provides rapid onset of action without the need for oral antipsychotic
      supplementation.

PMID- 29379295
TI  - Validation of Open-Heart Intraoperative Risk score to predict a prolonged
      intensive care unit stay for adult patients undergoing cardiac surgery with
      cardiopulmonary bypass.
AB  - Background: A prolonged stay in an intensive care unit (ICU) after cardiac
      surgery with cardiopulmonary bypass (CPB) increases the cost of care as well as
      morbidity and mortality. Several predictive models aim at identifying patients at
      risk of prolonged ICU stay after cardiac surgery with CPB, but almost all of them
      involve a preoperative assessment for proper resource management, while one - the
      Open-Heart Intraoperative Risk (OHIR) score - focuses on intra-operative
      manipulatable risk factors for improving anesthetic care and patient outcome.
      Objective: We aimed to revalidate the OHIR score in a different context.
      Materials and methods: The ability of the OHIR score to predict a prolonged ICU
      stay was assessed in 123 adults undergoing cardiac surgery (both coronary bypass
      graft and valvular surgery) with CPB at two tertiary university hospitals between
      January 2013 and December 2014. The criteria for a prolonged ICU stay matched a
      previous study (ie, a stay longer than the median). Results: The area under the
      receiver operating characteristic curve of the OHIR score to predict a prolonged
      ICU stay was 0.95 (95% confidence interval 0.90-1.00). The respective
      sensitivity, specificity, positive predictive value, and accuracy of an OHIR
      score of >=3 to discriminate a prolonged ICU stay was 93.10%, 98.46%, 98.18%, and
      95.9%. Conclusion: The OHIR score is highly predictive of a prolonged ICU stay
      among intraopera-tive patients undergoing cardiac surgery with CPB. The OHIR
      comprises of six risk factors, five of which are manipulatable intraoperatively.
      The OHIR can be used to identify patients at risk as well as to improve the
      outcome of those patients.

PMID- 29379296
TI  - Initial peri- and postoperative antibiotic treatment of infected nonunions:
      results from 212 consecutive patients after mean follow-up of 34 months.
AB  - Purpose: Infected nonunions of the long bones belong to the most feared
      complications in the field of orthopedic and trauma surgery. Optimal antibiotic
      therapy should start early with the first revision surgery. Therefore, the aim of
      this study was to evaluate our peri- and postoperative antibiotic regime in
      context with the microbial spectrum and antibiotic resistances of patients with
      infected nonunions and to assess the possible impact on healing rates. Methods:
      We included all patients with first revision surgery during 2010-2015 due to
      nonunion of long bones with a clinical history of infection treated with radical
      debridement, local application of a gentamicin-impregnated bone cement, and
      systemic cefuroxime. Mean follow-up was 34.2 months. Data collection was
      performed retrospectively using a computerized databank with information about
      microbial species from intraoperatively acquired tissue samples and respective
      antibiograms. Bone fusion rates were evaluated based on findings of the latest X
      rays and computed tomography scans. Results: Two hundred and twelve patients with
      nonunion and history of infection were selected; 171 patients had positive
      intraoperative microbial evidence of infection. Bacterial testing was mostly
      positive in fractures of the tibia (47.4%) and the femur (27.5%). Coagulase
      negative Staphylococcus spp. were the most frequently detected (44.4%) followed
      by mixed infections (18.7%) and Staphylococcus aureus (10.5%). Antibiograms
      revealed that 62.6% of our cases were cefuroxime sensitive; 87.7% were gentamicin
      sensitive. Only 10.5% showed resistance to both cefuroxime and gentamicin. There
      was no statistically significant difference of fusion rates between patients with
      different microbial species or different antibiograms. Conclusion: Our data
      suggest that besides the high variety of different detected species, initial
      antibiotic treatment with a combination of systemic cefuroxime and local
      gentamicin-loaded bone cement is effective and in almost 90% the later determined
      microbial infection was sensitive to this treatment. Therefore, we recommend
      initial treatment according to this algorithm until specific antibiograms are
      available from intraoperatively acquired tissue samples.

PMID- 29379297
TI  - Predictors of surgical outcomes after in situ ulnar nerve decompression for
      cubital tunnel syndrome.
AB  - Background: In the treatment of cubital tunnel syndrome (CuTS), in situ ulnar
      nerve decompression is commonly used. This study aims to investigate predictive
      factors for poor recovery and ulnar nerve instability following this procedure.
      Methods: We enrolled 235 patients who underwent in situ ulnar nerve decompression
      for the treatment of CuTS from January 2010 to December 2014. All patients
      underwent >2 years' follow-up. The primary outcome was postoperative recovery,
      which was assessed by Messina's criteria, and the secondary outcome was
      postoperative ulnar nerve instability. Potential risk factors were collected from
      demographic data and electrodiagnostic test, which included age, gender, body
      mass index, history of tobacco or alcohol use, history of major medical
      comorbidities, disease duration, preoperative severity, motor conduction
      velocity, and sensory conduction velocity. Results: A total of 208 patients
      (88.5%) had satisfactory outcomes, while the other 27 patients (11.5%) had not.
      There were 25 patients (10.6%) showing postoperative ulnar nerve instability
      during follow-up. The multivariate analysis showed that only severe preoperative
      symptom (odds ratio [OR], 3.06; 95% confidence interval [CI], 2.16-4.32) was
      associated with unsatisfactory postoperative outcomes in patients with CuTS
      (P<0.001). In the model investigating independent factors associated with
      postoperative ulnar nerve instability, we found that young age (OR, 2.41; 95% CI,
      1.63-3.58) was associated with the incidence of postoperative ulnar nerve
      instability (P<0.001). Conclusion: We found that severe preoperative symptom was
      associated with unsatisfactory postoperative outcomes, and young age was a risk
      factor for the incidence of postoperative ulnar nerve instability. Patients with
      these risk factors should be informed of the possibility of worse surgical
      outcomes.

PMID- 29379298
TI  - Raised serum uric acid is associated with higher bone mineral density in a cross
      sectional study of a healthy Indian population.
AB  - Purpose: Oxidative stress has been implicated as a fundamental mechanism in the
      decline of bone mass. Reactive oxygen species are reported to suppress osteoblast
      generation and differentiation and enhance osteoclast development and activity.
      Increasing evidence suggests favorable effect of serum uric acid (UA) on bone
      metabolism due to its antioxidant properties. Therefore, we investigated the
      association between serum UA levels and bone mineral density (BMD) in healthy
      adult Indian subjects. Materials and methods: We reviewed the medical records of
      524 subjects who had undergone preventive health check-ups in a tertiary care
      hospital that included UA and BMD measurements at femur neck, total femur, and
      lumbar spine. Subjects concomitantly taking drugs or having a medical condition
      that would affect the bone metabolism or UA levels were excluded. Results: The
      final analysis included 310 subjects (mean age: 47.2+/-12.2 years; females:
      43.5%; males: 56.5%). Study population was categorized into two groups based on
      the group median value for UA (ie, 5.4 mg/dL). BMD was significantly higher at
      all skeletal sites in subjects with UA >5.4 mg/dL compared to subjects with UA
      <=5.4 mg/dL (p<0.001). On correlation analysis, UA was positively associated with
      BMD at all skeletal sites (r=0.211-0.277; p<0.05). The correlation remained
      significant after controlling for age (p<0.05) and lifestyle factors (smoking,
      alcohol use, physical activity, and diet; p<0.05) independently. UA significantly
      (p<0.001) accounted for 4.5%-7.7% of the variance in BMD (r2=0.045-0.077) in
      unadjusted model and 1.6%-3.2% of the variance (p<0.05) when adjusted for age and
      body mass index combined at lumbar spine and right femur neck, respectively.
      Conclusion: We conclude that raised UA levels are associated with higher BMD at
      all skeletal sites and UA may have a protective role in bone metabolism owing to
      its antioxidant effect.

PMID- 29379299
TI  - Cancer stem cells, the ultimate targets in cancer therapy.

PMID- 29379300
TI  - The effects of naloxone on human breast cancer progression: in vitro and in vivo
      studies on MDA.MB231 cells.
AB  - Background: Naloxone is viewed as a specific competitive opioid antagonist acting
      at the level of opioid receptors (MU, delta, and kappa) with blended agonist
      adversary or agonist action. The role of naloxone in tumor cell growth has been
      poorly studied in human cancer cell lines. Materials and methods: In the present
      study, we report findings from in vitro and in vivo experiments performed to
      evaluate the effects of naloxone on human breast cancer cell growth and
      progression. In vitro assays were conducted on estrogen receptor-negative human
      breast carcinoma cells, MDA.MB231, treated with naloxone at different
      concentrations (10-100 MUM). In vivo experiments were performed on a mouse model
      of human triple-negative breast cancer generated by using MDA.MB231 injected
      subcutaneously in mice. Naloxone was daily intraperitoneally injected in mice at
      0.357 mg/kg for 2 weeks and at 0.714 mg/kg for the next 2 weeks. Microvessels
      formation was detected by fluorescein isothiocyanate-dextran (100 MUL) injected
      into the tail vein of mice and confirmed by immunohistochemistry with CD31 on
      mice tumor sections. Results: In vitro tests showed that the cell proliferation
      of MDA.MB231 was inhibited by naloxone in a dose-dependent manner, whereas the
      cell death was increased. In vivo studies demonstrated that tumors of mice
      treated with naloxone were significantly smaller than those observed in the
      control groups, as long as naloxone was administered. Finally, naloxone was not
      able to impair the microvessel formation in tumors of treated mice. Conclusion:
      Our data showed, for the first time, that naloxone reduced breast cancer
      progression without affecting angiogenesis.

PMID- 29379301
TI  - Autophagy suppresses proliferation of HepG2 cells via inhibiting glypican
      3/wnt/beta-catenin signaling.
AB  - Introduction: Autophagy plays an important role in the growth and survival of
      hepatocellular carcinoma (HCC) cells through several target proteins or signaling
      pathways. Glypican-3 (GPC3) is a new reliable HCC marker, which is involved in
      tumor growth in HCC, primarily mediated by wnt/beta-catenin signaling. Objective:
      The present study aimed to identify the role of autophagy in the proliferation of
      HepG2 cells through GPC3/wnt/beta-catenin signaling. Results and discussion:
      Results demonstrated that induction of autophagy by nutrition starvation and
      rapamycin treatment led to the downregulation of GPC3 expression in HepG2 cells,
      accompanied by the decreased expression of wnt downstream target genes (beta
      catenin, c-myc and cyclin D1). On the other hand, inhibition of autophagy by 3
      methyl adenine (3-MA) could rescue rapamycin-directed downregulation of GPC3 and
      wnt/beta-catenin target genes and augment the proliferation of HepG2 cells.
      Furthermore, interference of GPC3 by siRNA suppressed wnt/beta-catenin signaling
      and attenuated 3-MA stimulation of HepG2 cell proliferation. More interestingly,
      the mRNA of GPC3 remained unchanged when the protein levels of GPC3 were
      decreased by autophagy activation, suggesting that induction of autophagy may
      accelerate the degradation of GPC3. Conclusion: These results suggest that
      autophagy suppresses proliferation of HepG2 cells partially by inhibition of
      GPC3/wnt/beta-catenin signaling.

PMID- 29379302
TI  - RACKI induces chemotherapy resistance in esophageal carcinoma by upregulating the
      PI3K/AKT pathway and Bcl-2 expression.
AB  - Introduction: Accumulating evidence indicates that RACK1 is involved in the
      progression of tumors. We aimed to evaluate the function of RACK1 in esophageal
      squamous cell carcinoma (ESCC) and its role in the mechanism of chemotherapy
      resistance. Materials and methods: Transfected ESCC cell lines with plasmids
      expressed shRACK1 or open reading frame (ORF) targeting RACK1 and established
      stable cell lines. We then examined the effects of RACK1 on cell proliferation
      and chemotherapy resistance in ESCC cell lines, and the expression of AKT, pAKT,
      ERK1/2, Bcl-2, and Bim was introduced to further detect the association between
      RACK1 and chemotherapy resistance. Results: The proliferation ability of ESCC
      cells was improved in the overexpression RACK1 groups (P<0.001) and decreased in
      the transfected shRACK1 groups (P<0.001) compared with the control ones.
      Meanwhile, upregulation of RACK1 significantly suppressed cisplatin-induced
      apoptosis in Eca109 and EC9706 cells, while downregulation of RACK1 promoted the
      sensitivity compared to the control group (Eca109: P<0.001 for shRACK1, P<0.01
      for shNC, and P<0.001 for overexpression group; EC9706: P<0.001 for shRACK1,
      P<0.001 for shNC, and P<0.05 for overexpression group). Furthermore, we found
      that RACK1 could activate the PI3K/AKT pathway and increase the expression level
      of Bcl-2 in ESCC, which leads to the enhancement of chemoresistance in ESCC.
      Conclusion: RACK1 promotes proliferation and chemotherapy resistance in ESCC by
      activating the PI3K/AKT pathway and upregulating the Bcl-2 expression.

PMID- 29379303
TI  - Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of
      signaling pathways and molecular mechanisms of drug resistance.
AB  - Background: Ovarian cancer has the highest mortality rate among all the
      gynecological cancers. This is mostly due to the resistance of ovarian cancer to
      current chemotherapy regimens. Therefore, it is of crucial importance to identify
      the molecular mechanisms associated with chemoresistance. Methods: NCI/ADR-RES is
      a multidrug-resistant cell line that is a model for the study of drug resistance
      in ovarian cancer. We carried out a microarray-derived transcriptional profiling
      analysis of NCI/ADR-RES to identify differentially expressed genes relative to
      its parental OVCAR-8. Results: Gene-expression profiling has allowed the
      identification of genes and pathways that may be important for the development of
      drug resistance in ovarian cancer. The NCI/ADR-RES cell line has differential
      expression of genes involved in drug extrusion, inactivation, and efficacy, as
      well as genes involved in the architectural and functional reorganization of the
      extracellular matrix. These genes are controlled through different signaling
      pathways, including MAPK-Akt, Wnt, and Notch. Conclusion: Our findings highlight
      the importance of using orthogonal therapies that target completely independent
      pathways to overcome mechanisms of resistance to both classical chemotherapeutic
      agents and molecularly targeted drugs.

PMID- 29379304
TI  - miR-99a-5p acts as tumor suppressor via targeting to mTOR and enhances RAD001
      induced apoptosis in human urinary bladder urothelial carcinoma cells.
AB  - Introduction: miR-99a-5p, known to play an important role in mammalian target of
      rapamycin (mTOR) regulation, is downregulated in human bladder cancer. The study
      aimed to investigate the anticancer activity of miR-99a-5p and the possible
      mechanism associated with mTOR in bladder cancer cells. Materials and methods:
      Vectors expressing miR-99a-5p were transfected into human urinary bladder
      urothelial carcinoma (5637 and T24) cells. The level of miR-99a-5p was monitored
      by microRNA (miRNA) quantitative polymerase chain reaction (QPCR). Luciferase
      reporter assays were performed to verify the direct binding of miR-99a-5p to mTOR
      transcripts. The mTOR transcripts and protein levels were measured by QPCR and
      Western blot, respectively. Cell viability of miR-99a-5p-transfected cells was
      detected by tetrazolium salt (WST-1). Inhibition of mTOR complex 1 (mTORC1) and
      mTOR complex 2 (mTORC2) signaling was detected by the phosphorylation of mTOR and
      AKT using Western blot. The ability of miR-99a-5p to enhance RAD001-induced
      apoptosis was determined as the expression of cleaved caspase 3 and levels of DNA
      fragmentation. Results: Transfection of miR-99a-5p-expressing vector elevated the
      expression level of miR-99a-5p up to sixfold compared to vector-only controls.
      The results from luciferase assay verified that miR-99a-5p directly binds to the
      predicted sequence in the 3' untranslated region (3'-UTR) of mTOR. The levels of
      mTOR RNA and protein were decreased in miR-99a-5p-transfected cells. Dual
      inhibition of mTORC1 and mTORC2 by miR-99a-5p was confirmed by the decreased
      phosphorylation of mTOR (at Ser2448 and Ser2481), phospho-rpS6 and phospho-4EBP1.
      The phosphorylation of AKT was significantly inhibited in miR-99a-5p-transfected
      cells upon RAD001 treatment. Enforced expression of miR-99a-5p potentiated RAD001
      induced apoptosis in these cells. Conclusion: This is the first study showing
      that miR-99a-5p markedly inhibits the growth of bladder cancer cells via dual
      inhibition of mTORC1 and mTORC2. Our data demonstrated that forced expression of
      miR-99a-5p inhibits the feedback of AKT survival pathway and enhances the
      induction of apoptosis in RAD001-treated bladder cancer cells.

PMID- 29379305
TI  - A support vector machine and a random forest classifier indicates a 15-miRNA set
      related to osteosarcoma recurrence.
AB  - Background: Osteosarcoma, which originates in the mesenchymal tissue, is the
      prevalent primary solid malignancy of the bone. It is of great importance to
      explore the mechanisms of metastasis and recurrence, which are two primary
      reasons accounting for the high death rate in osteosarcoma. Data and methods:
      Three miRNA expression profiles related to osteosarcoma were downloaded from GEO
      DataSets. Differentially expressed miRNAs (DEmiRs) were screened using MetaDE.ES
      of the MetaDE package. A support vector machine (SVM) classifier was constructed
      using optimal miRNAs, and its prediction efficiency for recurrence was detected
      in independent datasets. Finally, a co-expression network was constructed based
      on the DEmiRs and their target genes. Results: In total, 78 significantly DEmiRs
      were screened. The SVM classifier constructed by 15 miRNAs could accurately
      classify 58 samples in 65 samples (89.2%) in the GSE39040 database, which was
      validated in another two databases, GSE39052 (84.62%, 22/26) and GSE79181 (91.3%,
      21/23). Cox regression showed that four miRNAs, including hsa-miR-10b, hsa-miR
      1227, hsa-miR-146b-3p, and hsa-miR-873, significantly correlated with tumor
      recurrence time. There were 137, 147, 145, and 77 target genes of the above four
      miRNAs, respectively, which were assigned to 17 gene ontology functionally
      annotated terms and 14 Kyoto Encyclopedia of Genes and Genomes pathways. Among
      them, the "Osteoclast differentiation" pathway contained a total of seven target
      genes and was analyzed further. Conclusion: The 15-miRNAs-based SVM classifier
      provides a potential useful tool to predict the recurrence of osteosarcoma. Our
      results suggest the possible mechanisms of osteosarcoma metastasis and recurrence
      and provide fresh DEmiRs as potential biomarkers or therapeutic targets for
      osteosarcoma.

PMID- 29379306
TI  - Retrospective analysis of relationships among the dose regimen, trough
      concentration, efficacy, and safety of teicoplanin in Chinese patients with
      moderate-severe Gram-positive infections.
AB  - Objectives: Teicoplanin, an antibiotic, has poor clinical efficacy when using the
      current drug label's recommended regimen, which is approved by the China Food and
      Drug Administration. This study explores the appropriate loading and maintenance
      doses of teicoplanin and evaluates the therapeutic target of teicoplanin trough
      concentration (minimum concentration [Cmin]). Subjects and methods: All patients
      treated with teicoplanin from February 2015 to August 2016 at Zhengzhou Central
      Hospital were screened for enrollment. A total of 113 subjects were included and
      then divided into four groups: A (received three to six doses at a loading dose
      of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), B
      (received three doses at a loading dose of 400 mg at 12-hour intervals, followed
      by maintenance dosing of 400 mg/day), C (received two doses at a loading dose of
      400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day), and D
      (received one to three doses at a loading dose of 400 mg at 12-hour intervals,
      followed by maintenance dosing of 200 mg/day). Cmin values of teicoplanin were
      detected with high-performance liquid chromatography on day 4, 30 minutes before
      maintenance-dose administration. Teicoplanin Cmin, efficacy, and safety were
      compared among the four groups. Results: Mean Cmin differed significantly among
      the four groups (A, 18.11+/-6.37 mg/L; B, 15.91+/-4.94 mg/L; C, 17.06+/-5.66
      mg/L; D, 11.97+/-3.76 mg/L) (P<0.001), with creatinine clearance of 89.62 (53.72
      162.48), 49.66 (40.69-59.64), 27.17 (9.7-39.45), and 96.6 (17.63-394.73) mL/min,
      respectively. The ratio of loading dose for 3 days to creatinine clearance and
      serum Cmin were significantly correlated (R=0.59, P<0.001). The correlation
      between the estimated probability of success and teicoplanin Cmin was assessed
      using binary logistic regression (OR 2.049, P<0.001). Hepatotoxicity- and
      nephrotoxicity-incidence rates did not significantly differ among the four groups
      (P=0.859 and P=0.949, respectively). Conclusion: A loading dose of 400 mg at 12
      hour intervals three to six times is needed to achieve the early target range (15
      20 mg/L) and improve the clinical efficacy rate for normal-renal-function
      patients. It is urgently necessary to amend the drug label for the recommended
      regimen.

PMID- 29379307
TI  - Performance of computed tomography versus chest radiography in patients with
      pulmonary tuberculosis with and without diabetes at a tertiary hospital in
      Riyadh, Saudi Arabia.
AB  - Background: Prior research suggests that diabetes mellitus (DM) is associated
      with increasing risk for developing cavitary lung disease in patients with
      pulmonary tuberculosis (TB). Additionally, chest computed tomography (CT) scan
      may be more sensitive than chest X-ray in detecting cavitary disease in such
      patients. The aim of this study was to compare the performance of chest CT to
      chest X-ray in detecting cavitary lung disease and to compare the frequency of
      cavities between TB patients with DM and without DM. Patients and methods: We
      conducted a retrospective cohort study at King Fahad Medical City, Riyadh, Saudi
      Arabia, from January 2004 to December 2015. We included patients aged 18 years
      and older with a positive sputum culture for Mycobacterium tuberculosis, and
      their medical charts were reviewed from admission to discharge. Results: Of the
      133 patients who met the inclusion criteria, 38 (28.6%) patients were known to
      have DM and were compared with 95 (71.4%) patients without DM. DM patients with
      glycated hemoglobin (HbA1c) >6.5% had significantly more cavitary lesions when
      compared to all patients (with or without DM) with HbA1c <6.4% and/or random
      blood sugar <200 mg/dL. Furthermore, CT was able to detect lung cavities in 58.8%
      of the patients who had negative chest X-ray findings for cavities. Conclusion:
      The presence of lung cavities was significantly associated with the presence of
      DM and levels of HbA1c in patients with pulmonary TB. CT scan in those with
      normal radiography increased the detection of cavities.

PMID- 29379308
TI  - Fractional erbium-doped yttrium aluminum garnet laser-assisted drug delivery of
      hydroquinone in the treatment of melasma.
AB  - Background: Melasma is a difficult-to-treat hyperpigmentary disorder. Ablative
      fractional laser (AFL)-assisted delivery of topically applied drugs to varied
      targets in the skin has been an area of ongoing study and research. Objective:
      The objective of this study was to evaluate the efficacy and safety of fractional
      erbium-doped yttrium aluminum garnet (Er:YAG) laser as an assisted drug delivery
      for enhancing topical hydroquinone (HQ) permeation into the skin of melasma
      patients. Patients and methods: Thirty female patients with bilateral melasma
      were randomly treated in a split-face controlled manner with a fractional Er:YAG
      laser followed by 4% HQ cream on one side and 4% HQ cream alone on the other
      side. All patients received six laser sessions with a 2-week interval. The
      efficacy of treatments was determined through photographs, dermoscopic
      photomicrographs and Melasma Area Severity Index (MASI) score, all performed at
      baseline and at 12 weeks of starting therapy. The patient's level of satisfaction
      was also recorded. Results: Er:YAG laser + HQ showed significantly better results
      (p<0.005) with regard to decrease in the degree of pigmentation as assessed on
      the 4-point scale than HQ alone. There was a significant decrease in MASI scores
      on Er:YAG laser + HQ side vs HQ side. Minor reversible side effects were observed
      on both sides. Conclusion: AFL-assisted delivery of HQ is a safe and effective
      method for the treatment of melasma.

PMID- 29379309
TI  - Comparison of linoleic acid-containing water-in-oil emulsion with urea-containing
      water-in-oil emulsion in the treatment of atopic dermatitis: a randomized
      clinical trial.
AB  - Background: Application of topical moisturizers is an essential part of the
      management of atopic dermatitis (AD). Linoleic acid (LA), the most abundant fatty
      acid in the epidermis, and its derivatives have an essential role in the
      structure and function of the epidermal barrier, and their defects are prominent
      in AD. The aim of this study was to compare the efficacy and safety of two
      cosmetic products containing either LA or urea in patients with AD. Patients and
      methods: A total of 20 patients with AD who met the eligibility criteria and
      provided written informed consents were enrolled in this randomized, intra
      individual split-body, single-center trial. Symmetrical lesions of patients were
      randomized for treatment with LA- or urea-containing water-in-oil (w/o) emulsions
      applied two to three times daily for 4 weeks. The efficacy of the two products
      was evaluated by local Scoring Atopic Dermatitis (SCORAD) of both lesions and
      also patient (or guardian) satisfaction. In addition, trans-epidermal water loss
      (TEWL), stratum corneum (SC) hydration, pH, sebum, temperature, erythema, melanin
      content, and ultrasonographic thickness and echo density of epidermis and dermis
      were measured before, and 2 and 4 weeks after, treatment. Results: Four weeks of
      treatment with the LA-containing product resulted in a significant decrease in
      local SCORAD, TEWL, erythema, and echo density of dermis, as well as an increase
      in SC hydration compared to baseline. The urea-containing product also reduced
      the local SCO-RAD and echo density of dermis and increased SC hydration. In
      contrast to the LA-containing product, changes in TEWL and erythema were not
      significant. Moreover, the reduction of erythema was significantly higher in the
      LA-containing product-treated side compared to the urea-containing product
      treated side (p = 0.006). Conclusion: Both LA- or urea-containing w/o emulsions
      can significantly improve barrier dysfunction and clinical severity of AD. In
      agreement with literature, it was confirmed that an LA-containing w/o emulsion
      exhibited erythema-reducing effects. Since emollients should be used on a regular
      basis, patients should choose a product by individual preference following
      recommendation by their dermatologists.

PMID- 29379310
TI  - Are energy drinks unique mixers in terms of their effects on alcohol consumption
      and negative alcohol-related consequences?
AB  - Introduction: Previous research has suggested that consuming alcohol mixed with
      energy drinks (AMED) increases overall alcohol consumption. However, there is
      limited research examining whether energy drinks are unique in their effects when
      mixed with alcohol, when compared with alcohol mixed with other caffeinated
      mixers (AOCM). Therefore, the aim of this survey was to investigate alcohol
      consumption on AMED occasions, to that on other occasions when the same
      individuals consumed AOCM or alcohol only (AO). Methods: A UK-wide online student
      survey collected data on the frequency of alcohol consumption and quantity
      consumed, as well as the number of negative alcohol-related consequences reported
      on AO, AMED and AOCM occasions (N=250). Results: Within-subjects analysis
      revealed that there were no significant differences in the number of alcoholic
      drinks consumed on a standard and a heavy drinking session between AMED and AOCM
      drinking occasions. However, the number of standard mixers typically consumed was
      significantly lower on AMED occasions compared with AOCM occasions. In addition,
      when consuming AMED, students reported significantly fewer days consuming 5 or
      more alcohol drinks, fewer days mixing drinks, and fewer days being drunk,
      compared with when consuming AOCM. There were no significant differences in the
      number of reported negative alcohol-related consequences on AMED occasions to
      AOCM occasions. Of importance, alcohol consumption and negative alcohol-related
      consequences were significantly less on both AMED and AOCM occasions compared
      with AO occasions. Conclusion: The findings that heavy alcohol consumption occurs
      significantly less often on AMED occasions compared with AOCM occasions is in
      opposition to some earlier claims implying that greatest alcohol consumption
      occurs with AMED. The overall greatest alcohol consumption and associated
      negative consequences were clearly associated with AO occasions. Negative
      consequences for AMED and AOCM drinking occasions were similar, suggesting that
      energy drink was comparable with AOCM in this regard.

PMID- 29379311
TI  - Postoperative discomfort and emergence delirium in children undergoing dental
      rehabilitation under general anesthesia: comparison of nasal tracheal intubation
      and laryngeal mask airway.
AB  - Background: Several studies have identified side effects of general anesthesia
      with endotracheal intubation, such as laryngeal pain, dysphonia, and
      postoperative nausea and vomiting (PONV). The laryngeal mask airway (LMAw) is
      believed to decrease these side effects. The aim of this trial was to compare
      postoperative discomfort, emergence delirium, and recovery time of patients who
      received either an LMAw or nasotracheal intubation (NTI). Patients and methods: A
      total of 70 children were randomly assigned to the LMAw group (n=35) or the NTI
      group (n=35). Both groups underwent mask induction with 8% sevoflurane. The NTI
      group received muscle relaxant, whereas the LMAw group did not. Postoperative
      laryngeal pain, dental pain, dysphonia, and PONV were assessed immediately and at
      1 hour and 6 hours postoperatively. The Wong-Baker Faces Scale was used to
      evaluate the patients' self-reported pain. In addition, decayed, missing, and
      filled teeth (dft/DMFT) values, dental procedure type, number of dental
      procedures, duration of the dental operation, duration of anesthesia, recovery
      time, emergence delirium, pediatric dentist's access to the mouth, and parents'
      satisfaction levels were recorded. Data were analyzed using descriptive
      statistics, chi-square tests, and two-sample t-tests. Results: The incidence of
      postoperative laryngeal pain was significantly higher in the NTI group
      immediately (97.2% vs. 8.5%, P=0.00), 1 hour (94.2% vs. 0%, P=0.00), and 6 hours
      postoperatively (25.7% vs. 0%, P=0.00). There were no statistically significant
      differences between the two groups in dental pain scores, dft/DMFT values,
      duration of anesthesia, duration of the dental operation, number of dental
      procedures, the incidence of PONV, or pediatric dentist's access to the mouth
      (P>0.05). Emergence delirium and recovery time were significantly higher in the
      NTI group (P<0.05). Conclusion: The LMAw provided a more comfortable
      postoperative period than NTI for children who underwent full-mouth dental
      rehabilitation under general anesthesia.

PMID- 29379312
TI  - Intra-articular ozone or hyaluronic acid injection: Which one is superior in
      patients with knee osteoarthritis? A 6-month randomized clinical trial.
AB  - Purpose: Knee osteoarthritis (OA) is a common disease, imposing a great burden
      through pain and decreased function. There are many therapeutic modalities
      including non-pharmacologic choices and oral, topical, and intra-articular
      medications. New studies have shown promising results for ozone application in
      knee OA. Our aim was to compare the effects of ozone therapy versus hyaluronic
      acid (HA) intra-articular injection in knee OA patients. Methods: In this
      randomized clinical trial, a total of 174 patients with more than 3 months of
      chronic pain or swelling in the knee joints along with consistent imaging
      findings were enrolled and randomly allocated into two groups of HA and ozone,
      which were planned to undergo 3 weekly injections of HA (Hyalgan(r)) and 10 mL of
      a 30 MUg/mL ozone solution, respectively. Patients were evaluated at baseline and
      6 months after the last injection for pain, stiffness, and function using the
      visual analog scale (VAS) and the Western Ontario and McMaster Universities
      Arthritis Index (WOMAC) questionnaire. Results: No major adverse events were
      detected in this study. Total WOMAC score decreased from 40.8+/-9.8 to 20.4+/-4.9
      (p<0.01) in the ozone group and from 38.5+/-7.9 to 17.1+/-4.2 (p<0.01) in the HA
      group. A similar trend was observed in pain improvement according to VAS. Pain,
      stiffness, and function significantly improved in both the groups, but no between
      group difference was found. Conclusion: Although both ozone and HA can be
      effectively used for improving function and reducing pain in selected knee OA
      patients, neither of the two showed any superiority at 6-month follow-up.

PMID- 29379313
TI  - A prospective, longitudinal study to evaluate the clinical utility of a
      predictive algorithm that detects risk of opioid use disorder.
AB  - Purpose: The purpose of this study was to determine the clinical utility of an
      algorithm-based decision tool designed to assess risk associated with opioid use.
      Specifically, we sought to assess how physicians were using the profile in
      patient care and how its use affected patient outcomes. Patients and methods: A
      prospective, longitudinal study was conducted to assess the utility of precision
      medicine testing in 5,397 patients across 100 clinics in the USA. Using a patent
      protected, validated algorithm combining specific genetic risk factors with
      phenotypic traits, patients were categorized into low-, moderate-, and high-risk
      patients for opioid abuse. Physicians who ordered precision medicine testing were
      asked to complete patient evaluations and document their actions, decisions, and
      perceptions regarding the utility of the precision medicine tests. The patient
      outcomes associated with each treatment action were carefully documented.
      Results: Physicians used the profile to guide treatment decisions for over half
      of the patients. Of those, guided treatment decisions for 24.5% of the patients
      were opioid related, including changing the opioid prescribed, starting an
      opioid, or titrating a patient off the opioid. Treatment guidance was strongly
      influenced by profile-predicted opioid use disorder (OUD) risk. Most importantly,
      patients whose physicians used the profile to guide opioid-related treatment
      decisions had improved clinical outcomes, including better pain management by
      medication adjustments, with an average pain decrease of 3.4 points on a scale of
      1-10. Conclusion: Patients whose physicians used the profile to guide opioid
      related treatment decisions had improved clinical outcomes, as measured by
      decreased pain levels resulting from better pain management with prescribed
      medications. The clinical utility of the profile is twofold. It provides
      clinically actionable recommendations that can be used to 1) prevent OUD through
      limiting initial opioid prescriptions and 2) reduce pain in patients at low risk
      of developing OUD.

PMID- 29379314
TI  - Experiences and attitudes about physical activity and exercise in patients with
      chronic pain: a qualitative interview study.
AB  - Purpose: The purpose of this study was to describe how patients with chronic pain
      experience physical activity and exercise (PA&E). Method: This qualitative
      interview study included 16 women and two men suffering from chronic pain and
      referred to a multimodal pain rehabilitation program. Semi-structured interviews
      were conducted and qualitative content analysis was used to analyze the
      interviews. Results: One main theme emerged: "To overcome obstacles and to seize
      opportunities to be physically active despite chronic pain." This main theme was
      abstracted from five themes: "Valuing a life with physical activity," "Physical
      activity and exercise - before and after pain," "A struggle - difficulties and
      challenges," "The enabling of physical activity," and "In need of continuous and
      active support." Conclusion: Although these participants valued PA&E, they seldom
      achieved desirable levels, and performance of PA&E was undermined by difficulties
      and failure. The discrepancy between the intention to perform physical activity
      and the physical activity accomplished could be related to motivation, self
      efficacy, and action control. The participants desired high-quality interaction
      with healthcare providers. The findings can be applied to chronic pain
      rehabilitation that uses PA&E as treatment.

PMID- 29379315
TI  - The rs4846049 polymorphism in the 3'UTR region of the MTHFR gene increases the
      migraine susceptibility in an Iranian population.
AB  - Introduction: Migraine is a painful complex neurovascular disease characterized
      by recurrent moderate-to-severe headaches. Increased level of homocysteine is
      related to dilation of cerebral vessels and endothelial injury that could trigger
      migraine attacks. Functional polymorphisms in the MTHFR gene affect homocysteine
      metabolism and, therefore, play an important role in the etiology of the disease.
      Objectives: We aimed to investigate the possible association between MTHFR gene
      rs4846049, C677T, and A1298C polymorphisms and the risk of migraine in Iranian
      population. Methods: In this genetic association study, 498 individuals were
      enrolled, including 223 migraine patients and 275 healthy controls. Genotyping
      was performed using tetra-primer ARMS-PCR for rs4846049 and PCR-restriction
      fragment length polymorphism for C677T and A1298C polymorphisms. Results: The
      association between rs4846049 and C677T polymorphisms and migraine was observed.
      For the rs4846049 polymorphism, the association was detected under a dominant
      model (P=0.007; odds ratio [OR] =0.60; 95% confidence interval [CI], 0.41-0.87),
      and for the C677T polymorphism, the TT genotype frequency was significantly
      different in the studied groups (P=0.009; OR =2.48; 95% CI, 1.25-4.92). No
      significant differences in the genotype or allele frequencies were found for the
      A1298C polymorphism between the migraineurs and controls. Conclusion: Present
      data provide evidence for the association of rs4846049 and C677T polymorphisms in
      the MTHFR gene and migraine. Further studies are required to validate the
      significance of the studied genetic variations in diverse ethnic populations.

PMID- 29379316
TI  - Masked hypertension and cardiovascular outcomes: an updated systematic review and
      meta-analysis.
AB  - Background: As many as one-third of individuals with normal office blood pressure
      (BP) are diagnosed with masked hypertension (HTN) based on ambulatory BP
      measurements (ABPM). Masked HTN is associated with higher risk of sustained HTN
      (SH) and increased cardiovascular morbidity. Methods: The present study was
      designed to systematically review cohort studies and assess the effects of masked
      HTN compared to normotension and SH on cardiovascular events and all-cause
      mortality. We systematically searched the electronic databases, such as MEDLINE,
      PubMed, Embase, and Cochrane for prospective cohort studies, which evaluated
      participants with office and ambulatory and/or home BP. Results: We included nine
      studies with a total number of 14729 participants (11245 normotensives, 3484
      participants with masked HTN, 1984 participants with white-coat HTN, and 5143
      participants with SH) with a mean age of 58 years and follow-up of 9.5 years.
      Individuals with masked HTN had significantly increased rates of cardiovascular
      events and all-cause mortality than normotensives and white-coat HTN and had
      lower rates of cardiovascular events than those with SH (odds ratio 0.61, 95%
      confidence interval 0.42-0.89; P=0.010; I2=84%). Among patients on
      antihypertensive treatment, masked HTN was associated with higher rates of
      cardiovascular events than in those with normotension and white-coat HTN and
      similar rates of cardiovascular events in those with treated SH. Conclusion:
      Prompt screening of high-risk individuals with home BP measurements and ABPM, the
      diagnosis of masked HTN, and the initiation of treatment, may mitigate the
      adverse cardiovascular effects of masked HTN.

PMID- 29379317
TI  - Effects of marital status on survival of hepatocellular carcinoma by
      race/ethnicity and gender.
AB  - Purpose: It is well demonstrated that being married is associated with a better
      prognosis in multiple types of cancer. However, whether the protective effect of
      marital status varied across race/ethnicity and gender in patients with
      hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the
      roles of race/ethnicity and gender in this relationship. Patients and methods: We
      identified eligible patients from Surveillance, Epidemiology and End Results
      (SEER) database during 2004-2012. Overall and cancer-specific survival
      differences across marital status were compared by Kaplan-Meier curves. We also
      estimated crude hazard ratios (CHRs) and adjusted hazard ratios (AHRs) with 95%
      confidence intervals (CIs) for marital status associated with survival by
      race/ethnicity and gender in Cox proportional hazard models. Results: A total of
      12,168 eligible patients diagnosed with hepatocellular carcinoma were included.
      We observed that married status was an independent protective prognostic factor
      for overall and cancer-specific survival. In stratified analyses by
      race/ethnicity, the AHR of overall mortality (unmarried vs married) was highest
      for Hispanic (AHR =1.25, 95% CI, 1.13-1.39; P<0.001) and lowest for Asian or
      Pacific Islander (AHR =1.13; 95% CI, 1.00-1.28; P=0.042). Stratified by gender,
      the AHR was higher in males (AHR =1.27; 95% CI, 1.20-1.33; P<0.001). Conclusion:
      We demonstrated that married patients obtained better survival advantages.
      Race/ethnicity and gender could influence the magnitude of associations between
      marital status and risk of mortality.

PMID- 29379318
TI  - The reciprocal relationship between coping mechanisms and lung cancer diagnosis:
      findings of a prospective study.
AB  - Background/purpose: Lung cancer is a major stress factor for the affected
      individual, leading to psychological distress in over 50% of the diagnosed
      patients. Since coping styles describe different patterns in approaching serious
      problems, our study aimed at ascertaining if the diagnosis of lung cancer has an
      impact on the patient's coping styles and if there is a difference in psychical
      response among patients with different coping styles, as assessed by variance of
      anxiety and depression scores after diagnosis. Patients and methods: In this
      prospective study, a cohort of 50 patients were evaluated using the COPE scale,
      Generalized Anxiety Disorder Questionnaire 7 (GAD-7), and Patient Health
      Questionnaire-9 (PHQ-9), both prior to and 1 month after learning about their
      lung cancer diagnosis. The baseline and the final parameters were compared and
      stratified with respect to coping styles. Results: We observed that 1 month after
      learning the diagnosis, the patients had a significantly higher GAD-7 score
      (median score 12 vs 4 points; p<0.001). At the same time, the PHQ-9 score was
      significantly higher at the 1 month follow-up time-point (median score 16 vs 7;
      p=0.002). The increases in the anxiety scores were significant in patients with
      initial social support (13 vs 3; p=0.014) and avoidance coping style (14 vs 6;
      p=0.003). Regarding the depression scores, after the diagnosis, the only
      significant increase was observed in patients with initial avoidance coping style
      (18 vs 5; p=0.014). Conclusion: Our study demonstrates that patients who receive
      the diagnosis for cancer show a significant increase in anxiety and depression
      intensity. The most adaptive coping style turned out to be the problem-focused
      one while the least adaptive one was the avoidant style.

PMID- 29379320
TI  - Erratum: Extraglottic airway devices: technology update [Corrigendum].
AB  - [This corrects the article on p. 189 in vol. 10, PMID: 28860875.].

PMID- 29379319
TI  - Pharyngeal electrical stimulation device for the treatment of neurogenic
      dysphagia: technology update.
AB  - Neurogenic dysphagia (ND) can occur in patients with nervous system diseases of
      varying etiologies. Moreover, recovery from ND is not guaranteed. The therapeutic
      approaches for oropharyngeal ND have drastically changed over the last decade,
      mainly due to a better knowledge of the neurophysiology of swallowing along with
      the progress of neuroimaging and neurophysiological studies. For this reason, it
      is a priority to develop a treatment that is repeatable, safe, and can be carried
      out at the bedside as well as for outpatients. Pharyngeal electrical stimulation
      (PES) is a novel rehabilitation treatment for ND. PES is carried out via location
      specific intraluminal catheters that are introduced transnasally and enable
      clinicians to stimulate the pharynx directly. This technique has demonstrated
      increasingly promising evidence in improving swallowing performance in patients
      with ND associated with stroke and multiple sclerosis, probably by increasing the
      corticobulbar excitability and inducing cortical reorganization of swallowing
      motor cortex. In this article, we update the reader as to both the physiologic
      background and past and current studies of PES in an effort to highlight the
      clinical progress of this important technique.

PMID- 29379321
TI  - Digital stethoscope: technology update.
AB  - Cardiovascular disease (CVD) is recognized as the leading cause of mortality
      throughout the world. About one-third of global mortality is attributable to CVD.
      In addition to clinical presentation, specific clinical exam findings can assist
      in treating and preventing CVD. CVD may initially manifest as pulmonary
      pathology, and thus, accurate cardiopulmonary auscultation is paramount to
      establishing accurate diagnosis. One of the most powerful tools available to
      physicians is the stethoscope. The stethoscope first emerged in the year 1818,
      invented by a French physician, Rene Laennec. Since then, the initial modest
      monaural wooden tube has evolved into a sophisticated digital device. This paper
      provides an analysis of the evolution of the stethoscope as well as highlights
      the advancement made by the modern digital stethoscope including the application
      of this tool in advancing care for patients suffering from CVD.

PMID- 29379322
TI  - Health-related quality of life in ANCA-associated vasculitis and item generation
      for a disease-specific patient-reported outcome measure.
AB  - Objective: The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides
      (AAVs) are multisystem diseases of the small blood vessels. Patients experience
      irreversible damage and psychological effects from AAV and its treatment. An
      international collaboration was created to investigate the impact of AAV on
      health-related quality of life (HRQoL), and develop a disease-specific patient
      reported outcome measure to assess outcomes of importance to patients. Methods:
      Patients with AAV from the UK, USA, and Canada were interviewed to identify
      salient aspects of HRQoL affected by AAV. The study was overseen by a steering
      committee including four patient research partners. Purposive sampling of
      interviewees ensured representation of a range of disease manifestations and
      demographics. Inductive analysis was used to identify themes of importance to
      patients; these were further confirmed by a free-listing exercise in the US.
      Individual themes were recast into candidate items, which were scrutinized by
      patients, piloted through cognitive interviews and received a linguistic and
      translatability evaluation. Results: Fifty interviews, conducted to saturation,
      with patients from the UK, USA, and Canada, identified 55 individual themes of
      interest within seven broad domains: general health perceptions, impact on
      function, psychological perceptions, social perceptions, social contact, social
      role, and symptoms. Individual themes were constructed into >100 candidate
      questionnaire items, which were then reduced and refined to 35 candidate items.
      Conclusion: This is the largest international qualitative analysis of HRQoL in
      AAV to date, and the results have underpinned the development of 35 candidate
      items for a disease-specific, patient-reported outcome questionnaire.

PMID- 29379323
TI  - Validation of liquid biopsy: plasma cell-free DNA testing in clinical management
      of advanced non-small cell lung cancer.
AB  - Plasma cell-free tumor DNA, or circulating tumor DNA (ctDNA), from liquid biopsy
      is a potential source of tumor genetic material, in the absence of tissue biopsy,
      for EGFR testing. Our validation study reiterates the clinical utility of ctDNA
      next generation sequencing (NGS) for EGFR mutation testing in non-small cell lung
      cancer (NSCLC). A total of 163 NSCLC cases were included in the validation, of
      which 132 patients had paired tissue biopsy and ctDNA. We chose to validate ctDNA
      using deep sequencing with custom designed bioinformatics methods that could
      detect somatic mutations at allele frequencies as low as 0.01%. Benchmarking
      allele specific real time PCR as one of the standard methods for tissue-based
      EGFR mutation testing, the ctDNA NGS test was validated on all the plasma derived
      cell-free DNA samples. We observed a high concordance (96.96%) between tissue
      biopsy and ctDNA for oncogenic driver mutations in Exon 19 and Exon 21 of the
      EGFR gene. The sensitivity, specificity, positive predictive value, negative
      predictive value, and diagnostic accuracy of the assay were 91.1%, 100% 100%,
      95.6%, and 97%, respectively. A false negative rate of 3% was observed. A subset
      of mutations was also verified on droplet digital PCR. Sixteen percent EGFR
      mutation positivity was observed in patients where only liquid biopsy was
      available, thus creating options for targeted therapy. This is the first and
      largest study from India, demonstrating successful validation of circulating cell
      free DNA as a clinically useful material for molecular testing in NSCLC.

PMID- 29379324
TI  - Bulimia nervosa in adolescents: prevalence and treatment challenges.
AB  - Bulimia nervosa (BN) is a serious psychiatric illness that typically develops
      during adolescence or young adulthood, rendering adolescents a target for early
      intervention. Despite the increasing research devoted to the treatment of youth
      with anorexia nervosa (AN) and adults with BN, there remains a dearth of evidence
      for treating younger individuals with BN. To date, there have been four published
      randomized controlled trials comparing psychosocial treatments, leaving
      significant room to improve treatment outcomes. Family-based treatment is the
      leading treatment for youth with AN, while cognitive-behavioral therapy is the
      leading intervention for adults with BN. Involving caregivers in treatment shows
      promising results, however, additional research is needed to investigate ways in
      which this treatment can be adapted further to achieve higher rates of recovery.

PMID- 29379325
TI  - A narrative review of binge eating disorder in adolescence: prevalence, impact,
      and psychological treatment strategies.
AB  - Binge eating disorder (BED) represents one of the most problematic clinical
      conditions among youths. Research has shown that the developmental stage of
      adolescence is a critical stage for the onset of eating disorders (EDs), with a
      peak prevalence of BED at the age of 16-17 years. Several studies among adults
      with BED have underlined that it is associated with a broad spectrum of negative
      consequences, including higher concern about shape and weight, difficulties in
      social functioning, and emotional-behavioral problems. This review aimed to
      examine studies focused on the prevalence of BED in the adolescent population,
      its impact in terms of physical, social, and psychological outcomes, and possible
      strategies of psychological intervention. The review of international literature
      was made on paper material and electronic databases ProQuest, PsycArticles, and
      PsycInfo, and the Scopus index were used to verify the scientific relevance of
      the papers. Epidemiological research that examined the prevalence of BED in
      adolescent samples in accordance with Diagnostic and Statistical Manual of Mental
      Disorders, 4th Edition showed a prevalence ranging from 1% to 4%. More recently,
      only a few studies have investigated the prevalence of BED, in accordance with
      the Diagnostic and Statistical Manual of Disorders, Fifth Edition criteria,
      reporting a prevalence of ~1%-5%. Studies that focused on the possible impact
      that BED may have on physical, psychological, and social functioning showed that
      adolescents with BED have an increased risk of developing various adverse
      consequences, including obesity, social problems, substance use, suicidality, and
      other psychological difficulties, especially in the internalizing area. Despite
      the evidence, to date, reviews on possible and effective psychological treatment
      for BED among young population are rare and focused primarily on adolescent
      females.

PMID- 29379326
TI  - Effect of combined gliclazide/metformin treatment on oxidative stress, lipid
      profile, and hepatorenal functions in type 2 diabetic patients.
AB  - Background: Type 2 diabetes is a chronic condition that requires pharmacotherapy
      interventions. Metformin and gliclazide are widely used drugs in monotherapy.
      However, their complementary action made utilization of the combination of these
      drugs an appealing approach. Aims: The study compared major therapeutic
      potentials of combined metformin/gliclazide treatment over metformin monotherapy
      based on the following parameters: oxidative stress, lipid profile, and
      hepatorenal functions. Subjects and methods: This is a comparative study was
      conducted from March 2015 to March 2016. The study screened 80 type 2 diabetic
      patients, of which 40 patients underwent combined metformin + gliclazide therapy
      (500 mg BD + 80 mg OD, respectively). The other 40 were matched for age and
      duration of diabetes mellitus with the previous group and received metformin
      monotherapy (500 mg BD). The levels of fasting blood glucose (FBG), total
      glycated hemoglobin (HbA1c), lipid peroxidation, total antioxidant capacity,
      serum creatinine, aspartate and alanine transaminases, total cholesterol,
      triglycerides, high-density lipoproteins, and low-density lipoproteins were
      measured according to the standard methods. Results: Oxidative stress, lipid
      profile, and hepatorenal functions were comparable in patients of both groups.
      However, patients on metformin treatment showed significantly lower levels of FBG
      [7.61 (6.70-8.89) mmol/L vs. 9.00 (7.30-10.68) mmol/L; P = .022] and HBA1c [7.00
      (6.40-7.65)% vs. 8.20 (7.20-9.75)%; P < .001] compared to those on combined
      therapy. Conclusion: Oxidative stress, lipids profile, and hepatorenal functions
      were not different in patients who were on combined metformin/gliclazide therapy
      and compared to those metformin alone. In contrast, glycemic control was poor in
      the diabetic patients undergoing combined therapy.

PMID- 29379327
TI  - Assessment of the association between drug disposal practices and drug use and
      storage behaviors.
AB  - Objective: Keeping unnecessary drugs at home is a situation showing both causes
      and consequences of irrational use of medicine. This study aimed to evaluate the
      approaches of a company's employees regarding drug storage, use, and disposal.
      Method: This online-based descriptive study was held in a multi-centered private
      sector company in a voluntary basis. The survey assessing participants' drug
      handling and storage behaviors was answered by 1121 employees from across eight
      provinces of Turkey in 2016. Main outcome measures were storage and disposal of
      unused/unwanted drugs at home in a rational way. Results: The percentage of
      participants who declared that they keep unused/unwanted drugs at home was 28.0%.
      About one-third of participants disposed their unused/unwanted drugs via the
      "garbage, sink, toilet, etc.". Participants >=30 years old and living with <4
      household members significantly tended to bring their unused/unwanted drugs to
      the company's drug-box. Nearly half of all participants (46.5%) stated a recent
      change in their disposal behavior. The vast majority of participants (94.6%) who
      previously took drugs back to the company's drug-box stated that they either had,
      or would, help their contacts adopt such behaviors. These participants were also
      significantly less likely to dispose of drugs inappropriately, practice self
      medication, be unaware of expired drugs at home, or fail to store drugs according
      to the labelling. Conclusion: While our findings showed that a substantial number
      of participants still had unused drugs at home and disposed of them
      inappropriately, it is understood that they started to exhibit more favorable
      behaviors in recent years.

PMID- 29379328
TI  - Bioactive epoxides and hydroperoxides derived from naturally monoterpene geranyl
      acetate.
AB  - Geranyl acetate (1) was oxidized thermally and photochemically using (mcpba,
      H2O2) respectively to obtain (E)-5-(3, 3-dimethyloxiran-2-yl)-3-methylpent-2-enyl
      acetate (2) and 3-(2-(3, 3-dimethyloxiran-2-yl) ethyl)-3-methyloxiran-2-yl)
      methyl acetate (3). On the other hand, photooxygenation of 1 with tetraphenyl
      porphin (TPP) as a photo sensitizer gave corresponding acitic acid 2,6-bis
      hydroperoxy-7-methyl-3-methylene-oct-7-enyl-ester (4), acitic acid 7-hydroperoxy
      3,7-dimethyl-octa-2,5-dienyl ester (5) and Acitic acid 3-hydroperoxy-7-methyl-3,7
      dimethyl-octa-1,6-dienyl ester (6). Antifungal studies were carried out on
      geranyl acetate and its derivatives. Studies on the antifungal activity
      especially Microsporum gypsum, Trichophyton vercossum and Candida tropicalis
      showed that geranyl acetate, its epoxide and hydroperoxide derivatives have good
      antifungal action.

PMID- 29379329
TI  - Perceptions and attitudes towards off-label dispensing for pediatric patients, a
      study of hospital based pharmacists in Jordan.
AB  - Background: With growing responsibility of the pharmacists in ensuring public
      health and safe medicine use, an understanding of the issues surrounding off
      label prescribing is crucial to allow pharmacists to make informed decisions
      about such practice. The aim of this study is to assess the perceptions and
      attitudes of hospital based pharmacists toward off-label medicine dispensing to
      children. Methods: After obtaining the required approvals, a validated
      questionnaire about off-label dispensing to pediatric patients was administered
      to 250 randomly selected hospital pharmacists. Results: One hundred and fifty
      (150) completed questionnaires were returned. Less than half of the respondents
      (44%, n = 66) admitted to being familiar with the concept of off-label
      dispensing, claiming to have obtained this knowledge basically through their
      dispensing experience rather than education. A minority of respondents (36%, n =
      54) reported dispensing off-label medicines within their practice knowingly. The
      majority of respondents had concerns regarding the efficacy (82%, n = 123) and
      safety (98%, n = 147) of off-label medicines. The most common reasons given by
      respondents for a dispensed prescription being off label were younger age than
      recommended (88%, n = 132). Most of respondents (94%, n = 141) claimed to double
      check the calculations of doses of medicines before dispensing off-label
      medicines and 60% (n = 90) of them felt that parents and guardians should be told
      when an off-label medicine has been prescribed for their children. Conclusion:
      The majority of respondents were not familiar with the concept of offlabel
      medicines. While reporting to have gained their knowledge from their professional
      experience, only a minority of respondents reported knowingly dispensing off
      label medicines for pediatric patients. Respondents indicated that manufacturing
      more appropriate formulations for pediatric patients would reduce such practices
      in this population. Having concerns regarding the efficacy and safety of off
      label medicines used for pediatric patients, respondents felt that the use of off
      label medicines would increase the likelihood of adverse drug reactions (ADRs).
      Finally, respondents felt that such practice of prescribing and dispensing should
      receive parental consent.

PMID- 29379330
TI  - Biological activities of the red algae Galaxaura rugosa and Liagora hawaiiana
      butters.
AB  - The biological activities; antimicrobial, antioxidant and anticancer, of the red
      algae Galaxaura rugosa and Liagora hawaiiana were determined. The total ethanol,
      lipoidal matters, chloroform, n-butanol, aqueous extracts and powder of both
      algae showed and bacterial and antifungal activities. However, the chloroform
      extract of Galaxaura rugosa showed antibacterial activity against Klebsiella
      pneumoniae (24 mm, 0.15 mg/ml) higher than gentamycin (23 mm, 0.49 mg/ml).
      Moreover, the total ethanol, lipoidal matter and chloroform extracts showed
      antifungal activity (21, 22 and 25 mm, 1.25, 0.312 and 0.156 mg/ml) similar to
      the antibiotic Ketoconazole activity (23, 24 and 27 mm, 1.25, 0.312 and 0.156
      mg/ml) against Aspergillus fumigatus, A. niger and Candida trobicalis,
      respectively. A good antioxidant activity (80.96%, IC50 = 27.8 ug/ml) was
      provided by Galaxaura rugosa. The anticancer activity results revealed that the
      lipoidal matters of Galaxaura rugosa and Liagora hawaiiana possessed antitumor
      activity (IC50 = 15 +/- 1.7 and 21.2 +/- 1.6, respectively) against lung
      carcinoma (A-549) better than vinblastine sulfate (IC50 = 24.6 +/- 0.7).
      Although, the lipoidal matters of Galaxaura rugosa and Liagora hawaiiana
      antitumor activity against cervical carcinoma (HeLa) and intestinal carcinoma
      (CACO-2) (IC50 = 10.2 +/- 0.6 and 12.2 +/- 0.6, respectively) preferable than
      vinblastine sulfate (IC50 = 59.7 +/- 2.1 and 30.3 +/- 1.4, respectively).

PMID- 29379331
TI  - Community pharmacy customer segmentation based on factors influencing their
      selection of pharmacy and over-the-counter medicines.
AB  - Background: Within the competitive pharmacy market environment, community
      pharmacies are required to develop efficient marketing strategies based on
      contemporary information about consumer behavior in order to attract clients and
      develop customer loyalty. Objectives: This study aimed to investigate the
      consumers' preferences concerning the selection of pharmacy and over-the-counter
      (OTC) medicines, and to identify customer segments in relation to these
      preferences. Methods: A cross-sectional study was conducted between February and
      March 2016 on a convenient quota sample of 300 participants recruited in the
      metropolitan area of Thessaloniki, Greece. The main instrument used for data
      collection was a structured questionnaire with close-ended, multiple choice
      questions. To identify customer segments, Two-Step cluster analysis was
      conducted. Results: Three distinct pharmacy customer clusters emerged. Customers
      of the largest cluster (49%; 'convenience customers') were mostly younger
      consumers. They gave moderate to positive ratings to factors affecting the
      selection of pharmacy and OTCs; convenience, and previous experience and the
      pharmacist's opinion, received the highest ratings. Customers of the second
      cluster (35%; 'loyal customers') were mainly retired; most of them reported
      visiting a single pharmacy. They gave high ratings to all factors that influence
      pharmacy selection, especially the pharmacy's staff, and factors influencing the
      purchase of OTCs, particularly previous experience and the pharmacist's opinion.
      Customers of the smallest cluster (16%; 'convenience and price-sensitive
      customers') were mainly retired or unemployed with low to moderate education, and
      low personal income. They gave the lowest ratings to most of the examined
      factors; convenience among factors influencing pharmacy selection, whereas
      previous experience, the pharmacist's opinion and product price among those
      affecting the purchase of OTCs, received the highest ratings. Conclusions: The
      community pharmacy market comprised of distinct customer segments that varied in
      the consumer preferences concerning the selection of pharmacy and OTCs, the
      evaluation of pharmaceutical services and products, and demographic
      characteristics.

PMID- 29379332
TI  - Antimicrobial, antioxidant and anticancer activities of Laurencia catarinensis,
      Laurencia majuscula and Padina pavonica extracts.
AB  - The antimicrobial, antioxidant, and anticancer activities of ethanolic extract of
      Laurencia catarinensis, L. majuscula and Padina pavonica were determined. The
      highest antibacterial activity; 23.40 +/- 0.58 mm (00.98 ug/ml) and 22.60 +/-
      2.10 mm (03.90 ug/ml) were obtained against Klebsiella pneumonia by Laurencia
      catarinensis and Padina pavonica, respectively. However, Padina pavonica showed
      excellent antibacterial activity against Bacillus subtilis (21.7 +/- 1.5 mm; 1.95
      ug/ml), Staphylococcus aureus (21.7 +/- 0.58 mm; 1.95 ug/ml), Streptococcus
      pyogenes (20.7 +/- 1.2 mm; 1.95 ug/ml) and Acinetobacter baumannii (20.1 +/- 1.2
      mm; 3.9 ug/ml). Moreover, the highest antifungal activity; 24.7 +/- 2.0 mm (0.98
      ug/ml), 23.7 +/- 1.5 mm (0.98 ug/ml), 23.6 +/- 1.5 mm (0.98 ug/ml) was obtained
      by Padina pavonica against Candida tropicalis, C. albicans and Aspergillus
      fumigatus, respectively. The algal extracts showed DPPH radical scavenging
      activity in a concentration-dependent manner with maximum scavenging activity
      (77.6%, IC50 = 5.59 ug/ml and 77.07%, IC50 = 14.3 ug/ml) was provided by Padina
      pavonica and Laurenica majuscula, respectively. The in vitro antitumor activity
      revealed that the IC50 values of Padina pavonica were 58.9, 115.0, 54.5, 59.0,
      101.0, 101.0, and 97.6 ug/ml; Laurencia catarinensis were 55.2, 96.8, 104.0,
      78.7, 117.0, 217.0, 169.0 ug/ml; and Laurencia. majuscula were 115.0, 221.0,
      225.0, 200.0, 338.0, 242.0, and 189.0 ug/ml; respectively against A-549 (Lung
      carcinoma), Caco-2 (Intestinal carcinoma), HCT-116 (Colon carcinoma), Hela
      (Cervical carcinoma), HEp-2 (Larynx carcinoma), HepG-2 (Hepatocellular
      carcinoma), and MCF-7 (Breast carcinoma) cell lines.

PMID- 29379333
TI  - Effect of polymer type on characteristics of buccal tablets using factorial
      design.
AB  - A two factor three level factorial design was used to investigate the effects of
      carbopol and cationic hydrophilic polymers which have a common use in buccal drug
      formulations. Statistical models with interaction terms were derived to evaluate
      influence of carbopol (X1) and chitosan (X2) on tablet disintegration (Y1) and
      dissolution (Y2), mechanical properties (Y3), swelling (Y4). Tablet
      disintegration studies were carried out using two different pH environments
      within buccal region pH limits and also two different commonly used dissolution
      methods for buccal tablets were also investigated to compare the effect of
      polymer type on dissolution. Polymer type and ratio affect the characteristics of
      the buccal tablets due to their different physicochemical behavior at buccal pH.
      Also significant variances between dissolution profiles for buccal tablets, using
      either USP Paddle or flow through cell methods were found. These results indicate
      that both polymer type and ratio as well as combination of them effects the drug
      behavior in different ways.

PMID- 29379335
TI  - Advancing pharmaceuticals and patient safety in Saudi Arabia: A 2030 vision
      initiative.
AB  - Low-quality medicines deliver sub-optimal clinical outcomes and waste precious
      health resources. It is important to ensure that public funds are spent on
      healthcare technologies that meet national regulatory bodies such as the Saudi
      Food and Drug Authority (SFDA), quality standards for safety, efficacy, and
      quality. Medicines quality is a complicated combination of pre-market regulatory
      specifications, appropriate sourcing of ingredients (active pharmaceutical
      ingredient (API), excipients, etc.), manufacturing processes, healthcare
      ecosystem communications, and regular and robust pharmacovigilance practices. A
      recent conference in Riyadh, sponsored by King Saud University, sought to discuss
      these issues and develop specific policy recommendations for the Saudi 2030
      Vision plan. This and other efforts will require more and more creative
      educational programs for physicians, pharmacists, hospitals, and patients, and,
      most importantly evolving regulations on quality standards and oversight by Saudi
      health authorities.

PMID- 29379334
TI  - Applications of nanoparticle systems in drug delivery technology.
AB  - The development of nanoparticle-based drug formulations has yielded the
      opportunities to address and treat challenging diseases. Nanoparticles vary in
      size but are generally ranging from 100 to 500 nm. Through the manipulation of
      size, surface characteristics and material used, the nanoparticles can be
      developed into smart systems, encasing therapeutic and imaging agents as well as
      bearing stealth property. Further, these systems can deliver drug to specific
      tissues and provide controlled release therapy. This targeted and sustained drug
      delivery decreases the drug related toxicity and increase patient's compliance
      with less frequent dosing. Nanotechnology has proven beneficial in the treatment
      of cancer, AIDS and many other disease, also providing advancement in diagnostic
      testing.

PMID- 29379336
TI  - Anti-ulcerative colitis activity of Calotropis procera Linn.
AB  - The aim of the present study was to evaluate the anti-ulcerative colitis activity
      of Calotropis procera. Different extracts of the investigated plant were
      evaluated; total alcohol extract, polar extract and non-polar extract. All the
      investigated extracts at doses 200 &400 mg/kg possessed a dose-dependent anti
      ulcerative colitis potential when administrated for 5 consecutive days after
      colitis induction by acetic acid in rats. They reduced different parameters of
      UC. Only polar extract at both doses (200, 400 mg/kg) was more effective than the
      standard drug Prednisolone (50 mg/kg), it produced percent protection of control
      colitis by 63.8% and78.4% respectively, while the standard drug Prednisolone
      produced 54.9% protection. The anti-ulcerative colitis activity may be attributed
      to the active principles i.e. flavonoids. Preliminary phytochemical screening
      showed that the plant contains flavonoids, unsaturated sterols and/or
      triterpenoides, cardiac glycosides, carbohydrates or glycosides, proteins and/or
      amino acids, tannins and coumarins. The total alcohol extract was safe up to 4000
      mg/kg and there were no side effects reported on liver and kidney functions.

PMID- 29379337
TI  - Measurement and evaluation of the effects of pH gradients on the antimicrobial
      and antivirulence activities of chitosan nanoparticles in Pseudomonas aeruginosa.
AB  - Objective: The purpose of this study was to study the antimicrobial activity of
      chitosan nanoparticles (CSNPs) on Pseudomonas aeruginosa with special emphasis on
      their sensitivity to pH and the effect of pH on their activity. Methodology:
      Antimicrobial activity of CSNPs against Pseudomonas aeruginosa at different pH
      was tested using broth dilution method. Further assessment of antivirulence
      activity and sensitization of CSNPs on Pseudomonas aeruginosa were examined.
      Results: Significant antimicrobial effects of CSNPs against Pseudomonas
      aeruginosa were detected at slightly acidic pH 5, whereas the activity was
      abolished at a pH of greater than 7. The antivirulence activity of CSNPs was then
      investigated and treatment with CSNPs (1000 ppm) resulted in a significant
      reduction or even complete inhibition of pyocyanin production by P. aeruginosa
      compared with untreated P. aeruginosa indicating the antivirulence activity of
      CSNPs. CSNPs also sensitized P. aeruginosa to the lytic effects of sodium dodecyl
      sulfate (SDS); such sensitization was not blocked by washing chitosan-treated
      cells prior to SDS exposure revealing that CSNPs disturb the outer membrane
      leading to irreversible sensitivity to detergent even at low concentration (100
      ppm). Conclusions: These findings highlight CSNPs as potentially useful as
      indirect antimicrobial agents for a variety of applications.

PMID- 29379338
TI  - Synthesis, structure, antioxidant activity, and water solubility of trolox ion
      conjugates.
AB  - The interaction of trolox with ammonia, alkylamines of different classes, and
      amino derivatives of heterocyclic compounds, including nitroxyl radicals and
      alkaloids, led to the production of ammonium salts called ion conjugates (ICs).
      Five ICs were characterised by X-ray diffraction. This is the first time a wide
      range of ICs were made from trolox with amines, and ESI-MS data demonstrated they
      have the potential to generate pseudomolecular [(A-B+) + H]+ ions. For all
      obtained trolox ICs, a significant increase (1-3 orders of magnitude) in water
      solubility was achieved while retaining high antioxidant activity. ICs
      synthesised from two biologically active fragments may be used to create
      polyfunctional agents with varying solubility and bioavailability.

PMID- 29379339
TI  - The patterns of children poisoning cases in community teaching hospital in
      Riyadh, Saudi Arabia.
AB  - Introduction: Although the majority of poisoning-related cases can be managed in
      home settings, reduction of hospital visits and admissions are still important
      challenge. Thousands of interventions are involved and the appropriate management
      of poisoning is therefore a major task and burden to any institution. Therefore,
      the present study was aimed to identify the most common classes of toxic
      substances and route of poisoning in children and to investigate the pattern of
      drug and chemical poisoning in suspected case fatalities, the subsequent need for
      hospital admission and arrival time to hospital. Methods: A retrospective cross
      sectional descriptive study of all registered poisoning cases of children
      reported to drug and poison information center at King Khaled University Hospital
      Riyadh, Saudi Arabia during the period of January 2010-December 2016. Results: A
      total of 735 children presented to Pediatric Emergency Medicine with poisoning.
      Most of the cases were asymptomatic, and majority of children were arrived to the
      hospital in less than 3 h. The drugs were the most common cause of poisoning
      (70%) followed by chemical materials (29%), which is more common in children
      under 2 years comparing to other groups (p < 0.001). The route of poisoning was
      oral in the majority of cases (98.8%). The drugs most frequently ingested were
      analgesic (18.8%). Among the chemicals, pesticide products involved in (39.6%) of
      the cases, followed by cleaning products (25.9%) and cosmetic (22.8%).
      Conclusion: The results found that the majority of poisoning cases occurred in
      children under the age of six and required only observation without treatment.
      These results necessitate the need for close cooperation between different
      governmental health-sectors to establish national epidemiological surveillance of
      poisoning events in Saudi Arabia to help to develop national plans to decrease
      the financial burden of emergency department congestion and hospital crowding.

PMID- 29379340
TI  - Pharmaceutical evaluation of different shampoo brands in local Saudi market.
AB  - Shampooing is the most common form of hair treatment. Shampoos are primarily
      products aimed at cleansing the hair and scalp. There are many brands of shampoos
      in Saudi Arabia, available from different sources, locally and imported from
      other countries. This study aims to investigate whether such brands comply with
      the Saudi standard specifications for shampoos, issued by the National Center for
      Specifications and Standards, and to what extent these specifications are
      applied. Six shampoo brands were randomly collected from Riyadh market
      (Pantene(r), Sunsilk(r), Herbal essences(r), Garnier Ultra Doux(r), Syoss(r) and
      L'Oreal Elvive(r)). The selected shampoos were evaluated according to their
      physicochemical properties, including organoleptic characterization, pH
      measurement, percentage of solid content, rheological measurements, dirt
      dispersion level, foaming ability and foam stability, and surface tension. All
      shampoos had a good percentage of solids, excellent foam formation with stable
      foam and a highly viscous nature. Regarding the pH measurement, all shampoo
      samples were within the specified range with good wetting ability.

PMID- 29379341
TI  - The psycho- and neurotropic profiling of novel 3-(N-R,R'-aminomethyl)-2-methyl-1H
      quinolin-4-ones in vivo.
AB  - The article presents the study of psycho- and neurotropic properties of novel 3
      (N-R,R'-aminomethyl)-2-methyl-1H-quinolin-4-ones in vivo. The research was
      carried out using the open field test, elevated plus maze, rotarod test, tail
      suspension test, passive avoidance test after scopolamine-induced amnesia and
      acute normobaric hypoxia with hypercapnia. As a result, two promising substances
      have been found. According to our results 3-[[(4-methoxyphenyl)amino]methyl]-2
      methyl-1H-quinolin-4-one in the dose of 10 mg/kg shows a specific sedative effect
      and a considerable anti-amnesic activity. The most interesting N-[(2-methyl-4-oxo
      1H-quinolin-3-yl)methyl]-N-phenylbenzamide (100 mg/kg) combines a potent anti
      anxiety action, the anti-amnesic activity and a considerable antihypoxic effect.
      They are of interest for further profound studies as promising psychoactive
      compounds.

PMID- 29379342
TI  - Safranal epoxide - A potential source for diverse therapeutic applications.
AB  - Safranal is an organic compound isolated from saffron oil. Photo epoxidation and
      thermal reactions of safranal can be a significant tool for the design of drugs
      to act as anticancer agents and potent chemoprevention. Safranal was subjected to
      oxidation reactions either thermally using m-chloroperbenzoic acid or
      photochemically with hydrogen peroxide. Photo chemically and thermally oxidation
      reaction gave the corresponding monoepoxy together with diepoxy derivatives. The
      primary tested of epoxide derivatives showed a moderate degree of DNA alkylation.
      Studies on the antimicrobial, especially Methicillin resistant Staphylococcus
      aureus (MRSA), showed high activity of safranal diepoxide (3) against the growth
      of bacteria Methicillin resistant Staphylococcus aureus (MRSA) more than safranal
      (1) and monoepoxide (2) respectively. The epoxidation products were tested
      against bacterium Methicillin resistant Staphylococcus aureus (MRSA).

PMID- 29379343
TI  - The utilization of nonprescription medications in Saudi patients with
      cardiovascular diseases.
AB  - Background: Cardiovascular diseases (CVDs) are the most common cause of disease
      related death in Saudi Arabia. The incidence of CVDs continues to increase,
      presenting a major health care problem. Nonprescription medications are widely
      used by patients with CVD and may cause adverse drug events, either by worsening
      the disease or by harmfully interacting with prescribed medications. We
      investigated the patterns of nonprescription medication utilization and the
      factors associated with their use in patients with CVD. Methods: This was a cross
      sectional study conducted at the Cardiology Clinics of an academic tertiary
      health care center. Participants were asked about their sociodemographic
      characteristics, medical history and frequency of using nonprescription
      medications including over-the-counter (OTC) products, dietary supplements, and
      herbal products. Moreover, we investigated the participants' sources of
      information about nonprescription medications. Multivariate logistic regression
      analysis was conducted to examine the predictors of nonprescription medication
      use. Results: A total of 209 participants were interviewed. The mean age of the
      participants was 56 +/- 15 years, and 110 (52.6%) were female. Of the 209
      participants, 116 (55%) reported routine use of nonprescription medications.
      Black seeds and garlic were the most frequently used herbal products.
      Acetaminophen, cold/cough remedies, and ibuprofen were the most commonly reported
      OTC drugs. Of the surveyed patients, 54 (46.5%) used nonprescription medications
      to manage cardiovascular conditions specifically. Compared with other
      comorbidities, diabetes mellitus was associated with a higher use of
      nonprescription medications. Conclusion: In patients with CVD, the routine use of
      nonprescription medications was common for a number of reasons. Health care
      providers should proactively discuss nonprescription use with their CVD patients
      to avoid potential harmful outcomes.

PMID- 29379344
TI  - Identification of medication discrepancies during hospital admission in Jordan:
      Prevalence and risk factors.
AB  - Objectives: Medication errors are considered among the most common causes of
      morbidity and mortality in hospital setting. Among these errors are discrepancies
      identified during transfer of patients from one care unit to another, from one
      physician care to another, or upon patient discharge. Thus, the aims of this
      study were to identify the prevalence and types of medication discrepancies at
      the time of hospital admission to a tertiary care teaching hospital in Jordan and
      to identify risk factors affecting the occurrence of these discrepancies.
      Methods: A three months prospective observational study was conducted at the
      department of internal medicine at Jordan university hospital. During the study
      period, 200 patients were selected using convenience sampling, and a pre-prepared
      data collection form was used for data collection. Later, a comparison between
      the pre-admission and admission medication was conducted to identify any possible
      discrepancies, and all of these discrepancies were discussed with the responsible
      resident to classify them into intentional (documentation errors) or
      unintentional. Linear regression analysis was performed to assess risk factors
      associated with the occurrence of unintentional discrepancies. Results: A total
      of 412 medication discrepancies were identified at the time of hospital
      admission. Among them, 144 (35%) were identified as unintentional while the
      remaining 268 (65%) were identified as intentional discrepancies. Ninety-four
      patients (47%) were found to have at least one unintentional discrepancy and 92
      patients (46%) had at least one documentation error. Among the unintentional
      discrepancies, 97 (67%) were found to be associated with a potential
      harm/deterioration to the patients. Increasing patients' age (beta = 0.195, p
      value = .013) and being treated by female residents (beta = 0.139, p-value =
      .045) were significantly associated with higher number of discrepancies.
      Conclusion: The prevalence of unintentional discrepancies at the time of hospital
      admission was alarmingly high. Majority of these discrepancies were associated
      with a potential harm to the patients. These findings support the necessity for
      implementing the medication reconciliation service in the country, engaging
      healthcare providers in the process of identification and resolution of
      medication discrepancies.

PMID- 29379345
TI  - An audit on parental attitudes towards medicines used in children.
AB  - Introduction: There is growing concerns regarding the use of medicines in
      children. Therefore, many strategies were implemented to improve such use and
      make safe and effective medicines more available for children. Enhancing
      interaction between parents and health care providers plays an important role in
      insuring the proper use of medicines. In order to optimize such interaction, the
      attitudes, beliefs and practices of parents toward medicine use in children need
      to be explored. Methods: A validated questionnaire was administered via face to
      face interviews to 1000 parents attending pediatric outpatient clinics with their
      children in order to investigate their attitudes toward children's medicines.
      Results: The majority of respondents (83.2%) were mothers. The majority
      participants (84.4%) agreed that medicines are necessary in treating illnesses,
      80% of the parents had worries about the side effects and interactions of
      medicines, and 60% of the parents said they try to avoid giving medicines to
      their children. Moreover, parents in this study varied considerably in their
      views toward prescription and over-the- counter medicines. More than half of the
      participants (55.2%) declared that doctors in Jordan prescribe antibiotics to
      children too easily. Conclusion: Participants had positive attitudes toward the
      necessity of medicines for ill children. However, a considerable proportion of
      the parents had negative attitudes toward children's medicines with respect to
      their side effects and interactions, their capability of disturbing the body's
      own capability of healing illnesses, their unnatural characteristic and other
      aspects related to medicines.

PMID- 29379346
TI  - Novel quinazoline and acetamide derivatives as safe anti-ulcerogenic agent and
      anti-ulcerative colitis activity.
AB  - Two novel quinazoline derivatives named as; 3-[(4-hydroxy-3-methoxy-benzylidene)
      amino]-2-p-tolyl-3H-quinazolin-4-one (5) and 2-p-Tolyl-3-[3,4,5-trimethoxy
      benzylidene-amino]-3H-quinazolin-4-one (6) in addition to one acetamide
      derivative named as 2-(2-Hydroxycarbonylphenylamino)-N-(4-aminosulphonylphenyl)
      11 were synthesized, and evaluated for their anti-ulcerogenic & Anti-Ulcerative
      colitis activities. All of the three compounds showed curative activity against
      acetic acid induced ulcer model at a dose of 50 mg/kg, they produced 65%, 85% &
      57.74% curative ratio for compounds 5, 6 & 11 respectively. The effect of the
      tested compounds 5, 6 & 11 at dose 50 mg/kg were significantly (P < 0.01) more
      effective than dexamesathone (0.1 mg/kg) in reducing all parameters. Compounds
      showed curative activity of for peptic ulcer (induced by absolute alcohol (at a
      dose of 50 mg/kg, it produced Curative of control ulcer 56.00%, 61.70% & 87.1%
      for compounds 5, 6 & 11 respectively at dose 50 mg/kg, while the standard drug
      (Omeprazole 20 mg/kg) produced 33.3%. In both tests, the activity of our target
      compounds were higher than the standard drugs used for treatment of peptic ulcer
      and ulcerative colitis. No side effects were reported on liver and kidney
      functions upon prolonged oral administration of this compounds.

PMID- 29379347
TI  - Association between satisfaction with and adherence to warfarin therapy on the
      control of international normalized ratio: A hospital-based study in Saudi
      Arabia.
AB  - Background: High satisfaction with, and adherence to, warfarin therapy are linked
      to better international normalized ratio (INR) control and good therapeutic
      outcomes. Objective: This study was conducted to identify the association between
      satisfaction with, and adherence to, warfarin therapy and the control of the INR
      within the target therapeutic range. Methods: A cross-sectional study was
      conducted from June 1 to August 31, 2016, at the Anticoagulation Clinic in the
      Cardiology Center at King Fahad Hospital, Qassim, Saudi Arabia. All adult
      patients included in the study were 18-years-old or older and were on warfarin
      therapy for 6 months or more. The data were collected through face-to-face
      interviews using a structured questionnaire. Results: A total of 298 patients
      were included. Of them, 194 patients (65.1%) were males and 152 (51.0%) were
      classified as satisfied with their warfarin therapy. Secondary educational level
      and above (P = .001) and being non-Saudi (P = .026) were identified as
      determinants of a high level of satisfaction. Ninety-five (31.8%) participants
      were classified as adherent to the therapy, and satisfaction with treatment was
      the only predictor of adherence (P = .009). One hundred thirty-six patients
      (45.6%) achieved their target INR range. Satisfaction (P = .038) and adherence (P
      = .023) were significantly associated with better INR control. Conclusion:
      Substantial efforts are needed to improve patient satisfaction and adherence to
      treatment through different strategies in order to achieve the target therapeutic
      goal for warfarin treatment.

PMID- 29379348
TI  - Triterpenoid modulates the salt tolerance of lanosterol synthase deficient
      Saccharomyces cerevisiae, GIL77.
AB  - This study examined the effect of triterpenoid on the salt tolerance of
      lanosterol synthase deficient yeast mutant GIL77. The expression of the
      triterpenoid synthase gene under GAL1 promoter in GIL77 increased the
      triterpenoid concentration of both whole cell and plasma membrane fractions.
      Without the induction of the genes, the growth curve of BgbAS or RsM1
      transformant depicted patterns similar to control cells in both the presence and
      absence of salt with growth inhibition at 500 mM NaCl. The induction of BgbAS and
      RsM1 gene expression slightly repressed growth compared with control cells in the
      absence of NaCl. The growth of GIL77 was significantly suppressed by the
      expression of BgbAS or RsM1 under salinity conditions. Of the triterpenoid
      synthase genes, BgbAS rather than RsM1 was found to strongly inhibit the growth
      of GIL77 cells under salt stressed conditions. The expression of the triterpenoid
      synthase gene in GIL77 also influenced their tolerance to other abiotic stresses.
      In contrast to the endogenous synthesis, the exogenous supply of triterpenoid in
      the culture medium appeared to occur in the plasma membrane fraction and enhanced
      the salt tolerance of GIL77. This study thus discussed the physiological
      significance of triterpenoid in relation to its possible role in modulating salt
      tolerance.

PMID- 29379349
TI  - Combination of intensity modulated radiotherapy followed treatment with p38 MAPK
      activation inhibitor inhibits the proliferation of MCF-7 breast cancer cells.
AB  - The present study was aimed to investigate the effect of intensity modulated
      radiotherapy (IMRT) followed by treatment with inhibitor for p38 MAPK, SB203580
      on the rate of proliferation in drug resistant MCF-7 breast cancer cells.
      Interestingly, the results from immuno histochemistry and western blot assays
      revealed higher level of distribution of activated p38 MAPK in the drug resistant
      breast cancer tissues compared to the primary tissues. Treatment of the drug
      resistant MCF-7 cells with SB203580 led to a significant decrease in the
      phosphorylation of p38 MAPK. Exposure to IMRT caused a significant decrease in
      the rate of proliferation in drug resistant MCF-7breast cancer cells (P < 0.05).
      MCF-7 cells were subjected to IMRT for 45 min followed by treatment with SB203580
      for 12 h. The results from MTT assay revealed inhibition in the rate of
      proliferation of MCF-7 cells more efficiently compared to the IMRT or SB203580
      when used separately (P < 0.02). The effect of IMRT and SB203580 on inhibition of
      MCF-7 cell proliferation showed synergistic relation. Since MAPK signaling
      pathway plays an important role in the development of drug resistance, therefore,
      inhibition of p38 MAPK activation by the combination of IMRT followed by
      treatment with inhibitor for p38 MAPK can be a promising strategy for breast
      cancer treatment. Thus combination of IMRT exposure and treatment with SB203580
      can be used for the inhibition of drug resistant breast cancer.

PMID- 29379350
TI  - Comparative phytochemical profiling of different soybean (Glycine max (L.) Merr)
      genotypes using GC-MS.
AB  - This study aimed to estimate the proximate, phenolic and flavonoids contents and
      phytochemicals present in seeds of twenty four soybeans (Glycine max (L.) Merr)
      genotypes to explore their nutritional and medicinal values. Crude protein
      composition ranged between 35.63 and 43.13% in Argentinian and USA (Clark)
      genotypes, respectively. Total phenolic content varied from 1.15 to 1.77 mg
      GAE/g, whereas flavonoids varied from 0.68 to 2.13 mg QE/g. The GC-MS analysis
      resulted identification of 88 compounds categorized into aldehydes (5), ketones
      (13), alcohols (5), carboxylic acids (7), esters (13), alkanes (2), heterocyclic
      compounds (19), phenolic compound (9), sugar moiety (7) ether (4) and amide (3),
      one Alkene and one fatty acid ester. Indonesian genotypes (Ijen and Indo-1) had
      the highest phenolic compounds than others genotype having antioxidant
      activities, while the Australian genotype contains the maximum in esters
      compounds. The major phytocompounds identified in majority of genotypes were
      Phenol, 2,6-dimethoxy-, 2-Methoxy-4-vinylphenol, 3,5-Dimethoxyacetophenone, 1,2
      cyclopentanedione and Hexadecanoic acid, methyl ester. The presence of
      phytochemicals with strong pharmacological actions like antimicrobial and
      antioxidants activities could be considered as sources of quality raw materials
      for food and pharmaceutical industries. This study further set a platform for
      isolating and understanding the characteristics of each compound for it
      pharmacological properties.

PMID- 29379351
TI  - Pharmacological credence of the folklore use of Bauhinia malabarica in the
      management of jaundice.
AB  - The information on the hepatoprotective effect of Bauhinia malabarica Roxb.
      (Family Leguminosae) used in the folkloric medical practice in Malabar coast and
      Walayar valley of southern India for the treatment of liver related disorders is
      completely unknown. Hence, the efficacy of the aqueous methanolic extract of stem
      bark of B. malabarica (AqMeOH-Ba) was evaluated for liver function serum
      biochemical markers along with the antioxidant markers in liver tissues of Wistar
      albino rats. The biochemical observations as well as the histopathological
      examination of liver sections manifested considerable hepatoprotective activity
      of B. malabarica stem bark, and thus validated the folkloric claim.

PMID- 29379352
TI  - The intertwine of nanotechnology with the food industry.
AB  - The past decade has proven the competence of nanotechnology in almost all known
      fields. The evolution of nanotechnology today in the area of the food industry
      has been largely and has had a lot of contribution in the food processing, food
      package, and food preservation. The increasing global human population has come
      with growing population to be fed, and food production is not adjusted to at par
      with the growing population. This mismatch has shown the real essence of food
      preservation so that food products can reach to people on a global scale. The
      introduction of nanotechnology in the food industry has made it easy to transport
      foods to different parts of the world by extending the shelf-life of most food
      products. Even with this beneficial aspect of nanotechnology, it has not been
      proven an entire full-proof measure, and the field is still open to changing
      technology. It suffices to note that nanotechnology has to a big extent succeed
      in curbing the extent of food wastage due to food spoilage by the microbial
      infestation. Nanotechnology has focused on fresh foods, ensuring a healthier food
      by employing nano-delivery systems in the process. The delivery systems are the
      ones, which carries the food supplements. However, these are certain sets of
      regulations that must be followed to tame or control the health related risks of
      nanotechnology in food industries. This paper outlines the role of nanotechnology
      at different levels of the food industry including, packaging of food, processing
      of food and the various preservation techniques all aiming to increase the shelf
      life of the food products.

PMID- 29379353
TI  - Assessment of gender-related differences in vitamin D levels and cardiovascular
      risk factors in Saudi patients with type 2 diabetes mellitus.
AB  - Diabetes is a major risk factor for cardiovascular disease (CVD) including
      stroke, coronary heart disease, and peripheral artery disease. It remains a
      leading cause of mortality throughout the world, affecting both women and men.
      This investigation was aimed to study gender based differences in cardiovascular
      risk factors of adult population with type-2 diabetes mellitus (T2DM) and to
      check the correlation between serum HbA1C, lipid profile and serum vitamin D
      levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross
      sectional study involving subjects was divided into two gender based groups;
      normal male (800), diabetic male (800) and normal female (800) and T2DM females
      (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total
      cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL
      C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)
      vitamin D in all groups. All the glycemic control parameters and lipid profile
      parameters were found to be significantly different in diabetic vs non-diabetic
      group (p < 0.001) in both genders. The results also show that vitamin D
      concentration decreased significantly (p < 0.001) in diabetic patients than the
      healthy individuals in both the genders. Vitamin-D and HbA1C were negatively
      correlated in both males and females in T2DM patients and significant at P <
      0.05. Our study reveals that dyslipidemia remains one of the major risk factors
      of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D
      associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.

PMID- 29379354
TI  - Potentiation of antibiotic activity by Passiflora cincinnata Mast. front of
      strains Staphylococcus aureus and Escherichia coli.
AB  - The development of new drugs from plants is an interesting alternative approach
      to overcoming microbial resistance. Passiflora cincinnata shows resistance to
      diseases and pests and a higher concentration of chemical components that may be
      useful in the pharmaceutical industry. We investigated the potential
      antimicrobial and antibiotic-modifying activity of hydroalcoholic extracts of
      leaves, stems, bark, pulp and seeds of P. cincinnata. The extracts were prepared
      by homogenization of material in 50% ethanol. Minimum inhibitory concentration
      (MIC) was determined by the broth dilution method, and the bacterial strains
      tested were Staphylococcus aureus and Escherichia coli. Antibiotic-modifying
      activity was evaluated against the strains S. aureus 03 and E. coli 08, using a
      subinhibitory concentration of extract. The antibiotics tested were: amikacin,
      gentamicin, ampicillin, potassium benzylpenicillin and oxacillin. The extracts
      did not show antimicrobial activity of clinical relevance, where the MIC was
      equal to or greater than 1024 MUg/mL. S. aureus showed 13 events, while E. coli
      showed only 4 events. Among these events, 14 involved synergistic activity,
      potentiating the effect of the antibiotics, and only 3 events demonstrated
      antagonistic activity toward ampicillin. Hydroalcoholic extracts are potential
      antimicrobial agents when combined with conventional drugs little utilized in in
      vivo treatment.

PMID- 29379355
TI  - Isolation of antimicrobial producing Actinobacteria from soil samples.
AB  - Emergence of multidrug resistant bacteria has made the search for novel bioactive
      compounds from natural and unexplored habitats a necessity. Actinobacteria have
      important bioactive substances. The present study investigated antimicrobial
      activity of Actinobacteria isolated from soil samples of Egypt. One hundred
      samples were collected from agricultural farming soil of different governorates.
      Twelve isolates have produced activity against the tested microorganisms (S.
      aureus, Bacillus cereus, E. coli, K. pneumoniae, P. aeruginosa, S. Typhi, C.
      albicans, A. niger and A. flavus). By VITEK 2 system version: 07.01 the 12
      isolates were identified as Kocuria kristinae, Kocuria rosea, Streptomyces
      griseus, Streptomyces flaveolus and Actinobacteria. Using ethyl acetate
      extraction method the isolates culture's supernatants were tested by diffusion
      method against indicator microorganisms. These results indicate that
      Actinobacteria isolated from Egypt farms could be sources of antimicrobial
      bioactive substances.

PMID- 29379356
TI  - Effect of sevoflurane and halothane anesthesia on cognitive function and immune
      function in young rats.
AB  - In the current study, we scrutinized the effect of sevoflurane and halothane on
      cognitive and immune function in young rats. The rats were divided into following
      groups: sevoflurane, halothane and sevoflurane + halothane groups, respectively.
      The rats were regularly treated with the pre-determined treatment. We also
      scrutinized the serum proinflammatory cytokines including IL-10, IL-4 and IL-2;
      brain level IL-1beta; hippocampal neuronal apoptosis concentration were
      estimated. The water maze test was performed in rats for the estimation of
      cognitive ability. During the water maze test, on the 1st day the sevoflurane
      group showed the latency; sevoflurane and sevoflurane + halothane group
      demonstrated the declined latency gradually as compared to the control group rats
      after the 3 days. The latency of the control, halothane, sevoflurane + halothane
      group rats showed the reduced latency and also showed the reduced crossing circle
      times. The hippocampal neuron apoptosis was significantly increased in halothane
      and sevoflurane + halothane group as compared to control group rats,
      respectively. Control group rats demonstrated the increased neuron apoptosis. The
      proinflammatory cytokines including IL-10 and IL-4 was significantly higher in
      sevoflurane, halothane and sevoflurane + halothane group rats after anesthesia
      and the whole brain IL-1beta was significantly decrease in the sevoflurane,
      halothane and sevoflurane + halothane as compared to control group. Sevoflurane
      can inhibit the anesthesia effect of halothane on the immune and cognitive
      function of rats.

PMID- 29379357
TI  - Larvicidal, ovicidal activities and histopathological alterations induced by
      Carum copticum (Apiaceae) extract against Culex pipiens (Diptera: Culicidae).
AB  - An experiment was carried out, firstly, to determine the possible toxicity of
      Carum copticum (Apiaceae) extract against Culex pipiens (Diptera: Culicidae),
      and, secondly, to study the histopathological alterations in the midgut of Cx.
      pipiens as a result of treatment with C. copticum extract. Larvicidal and
      ovicidal activities of C. copticum extract against the larvae of Cx. pipiens was
      determined according to World health organization (WHO). The inhibition effect of
      C. copticum was assessed by determining the mortality of the treated larvae and
      eggs. The histopathological effect of the C. copticum extracts on midgut
      epithelium of the larvae was examined under both light and transmission electron
      microscopy. The crude extract of C. copticum exerted 100% mortality for Cx.
      pipiens after 24 h at 200 MUm/ml, and zero hatchability (100% mortality) at 150
      MUm/ml for Cx. pipiens. The histopathological study showed that larvae treated
      with C. copticum extract had cytopathological alterations of the midgut
      epithelium. The study provided information on various effects of C. copticum
      extract against Cx. pipiens.

PMID- 29379358
TI  - Changes in carotenoid and chlorophyll content of black tomatoes (Lycopersicone
      sculentum L.) during storage at various temperatures.
AB  - Black tomatoes have a unique color and higher lycopene content than typical red
      tomatoes. Here, black tomatoes were investigated how maturation stage and storage
      temperature affected carotenoid and chlorophyll accumulation. Immature fruits
      were firmer than mature fruits, but failed to develop their distinctive color and
      contained less lycopene when stored at 8  degrees C. Hunter a* values of black
      tomatoes increased with storage temperature and duration; storage of immature
      fruits at high temperature favored lycopene accumulation. Chlorophyll levels of
      black tomatoes declined during storage, but differences between mature and
      immature tomatoes stored at 12  degrees C were minimal. beta-Carotene levels of
      black tomatoes increased during early storage, but rapidly declined beginning 13
      d post-harvest. The highest lycopene and chlorophyll levels were observed in
      mature black tomatoes stored at 12  degrees C for 13 d; these conditions also
      yielded the best quality fruit. Thus, the unique pigmentation properties of black
      tomatoes can be precisely controlled by standardizing storage conditions.

PMID- 29379359
TI  - Effects of Panax ginseng on the nerve growth factor expression in testosterone
      induced benign prostatic hyperplasia.
AB  - The prostatic hyperplasia in benign prostatic hyperplasia (BPH) leads to
      obstructive micturition symptoms. Previous studies showed that pontine
      micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial
      preopticnucleus (MPA) regions in the brain have been known to regulate the
      urinary bladder function. The present study shows the influences of Panax ginseng
      on nerve growth factor (NGF) expressions in PMC, vlPAG, and MPA regions in the
      brain. Wistar rats were used for the present study. The rats split into four
      groups; 4 groups (n = 6) in control group, BPH-induced group, BPH-induced and P.
      ginseng-treated group, and BPH-induced and finasteride-treated group. BPH in rats
      was induced by testosterone and the animals were evaluated for NGF expression in
      PMC, vlPAG, and MPA regions in the brain. The NGF expression was identified using
      immunohistochemistry (IHC). The NGF expression by IHC showed spots with dark
      brown color. In our results, NGF expressions in PMC, vlPAG, and MPA regions in
      the brainstem of the BPH-induced group showed increase than the control animal.
      These increased NGF expressions in three regions were decreased using treatment
      with P. ginseng (200 mg/kg). These results suggest that P. ginseng has
      therapeutic effects on the symptoms of BPH and is associated with the regulation
      of NGF expression in the brain. In conclusion, the administration of P. ginseng
      helps nerve growth factor activation.

PMID- 29379360
TI  - Molecular characterization of glucosinolates and carotenoid biosynthetic genes in
      Chinese cabbage (Brassica rapa L. ssp. pekinensis).
AB  - The present study aimed to investigate the contents of glucosinolates (GSLs) and
      carotenoids in eleven varieties of Chinese cabbage in relation to the expression
      level of the important transcription factors. MS and HPLC analysis identified the
      presence of 13 GSLs (progoitrin, sinigrin, glucoalyssin, gluconapoleiferin,
      gluconapin, glucocochlearin, glucobrassicanapin, glucoerucin, 4
      hydroxyglucobrassicin, glucobrassicin, 4-methoxyglucobrassicin, neoglucobrassicin
      and gluconasturtiin) and four carotenoids (lutein, zeaxanthin, alpha-carotene and
      beta-carotene). GSL contents were varied among the different cabbage varieties.
      The total GSL content ranged from 2.7 to 57.88 MUmol/g DW. The proportion of
      gluconapin (54%) and glucobrassicanapin (22%) was higher in all the varieties,
      respectively. Results documented the variation in total and individual carotenoid
      contents that have also been observed among different varieties; however, the
      total carotenoid contents ranged from 289.12 to 1001.41 mg kg-1 DW (mean 467.66).
      Interestingly, the proportion of lutein (66.5) and beta-carotene (25.9) were
      higher than alpha-carotene (5.1) and zeaxanthin (2.5%). Consequently, the
      expression level of the regulatory gene, MYB28 was higher in 'K0648' and was
      directly proportional to GSL content. Similarly, the expression levels of 1-PSY
      were higher in 'K0112'; however, the expression levels of 2-ZDS, 3-LCYB, 4-LCYE,
      5-CHXB and 7-NCED genes showed no significant difference. In addition, the
      correlation between GSL and carotenoid contents and gene expression level showed
      moderate significant difference in each Chinese cabbage.

PMID- 29379362
TI  - Food habits of the Arabian skink, Scincus hemprichii Wiegmann, 1837, (Sauria:
      Scincidae), in the Southwest Saudi Arabia.
AB  - Food and feeding habits of the Arabian skink, Scincus hemprichii were
      investigated in Jazan province, southwest of Saudi Arabia. S. hemprichii
      individuals fed during eleven months of the year. The mass of food in the
      stomachs indicated that a high degree of foraging success occurred during the
      warm spring while the lowest was during winter with January as an exception to
      feeding by the lizard. Analysis of the contents of 60 stomachs revealed that the
      diet of S. hemprichii in the study area consisted of arthropods, with two species
      of beetles of the family Dermestidae (Dermestis vulpinus and Dermestis maculates)
      and three type of dipteran larvae, accounting for 76% of the total volume of the
      food items. Specimens collected during January had empty stomachs.

PMID- 29379361
TI  - Molecular genetic studies in Saudi population; identified variants from GWAS and
      meta-analysis in stroke.
AB  - Introduction: Stroke is a multifactorial and heterogeneous disorder, correlates
      with heritability and considered as one of the major diseases. The prior reports
      performed the variable models such as genome-wide association studies (GWAS),
      replication, case-control, cross-sectional and meta-analysis studies and still,
      we lack diagnostic marker in the global world. There are limited studies were
      carried out in Saudi population, and we aim to investigate the molecular
      association of single nucleotide polymorphisms (SNPs) identified through GWAS and
      meta-analysis studies in stroke patients in the Saudi population. Methods: In
      this case-control study, we have opted gender equality of 207 cases and 207
      controls from the capital city of Saudi Arabia in King Saud University Hospital.
      The peripheral blood (5 ml) sample will be collected in two different
      vacutainers, and three mL of the coagulated blood will be used for lipid analysis
      (biochemical tests) and two mL will be used for DNA analysis (molecular tests).
      Genomic DNA will be extracted with the collected blood samples, and specific
      primers will be designed for the opted SNPs (SORT1-rs646218 and OLR1-rs11053646
      polymorphisms) and PCR-RFLP will be performed and randomly DNA sequencing will be
      carried out to cross check the results. Results: The rs646218 and rs11053646
      polymorphisms were significantly associated with allele, genotype and dominant
      models with and without crude odds ratios (OR's) and Multiple logistic regression
      analysis (p < 0.05). Correlation between lipid profile and genotypes has
      confirmed the significant relation between triglycerides and rs646218 and
      rs1105364 6polymorphisms. However, rs11053646 polymorphism was correlated with
      HDLC (p = 0.04). Genotypes were examined in both males' vs. males and females'
      vs. females in cases and control and we concluded that in rs11053646
      polymorphisms with male subjects compared between cases and controls found to be
      associated with dominant model heterozygote genotypes (p < 0.05). Conclusion: The
      results of the current study confirmed the SORT1 and OLR1 SNPs were associated in
      the Saudi population. The current results were in the association with the prior
      study results documented through GWAS and meta-analysis association. However,
      other ethnic population studies should be performed to rule out in the human
      hereditary diseases.

PMID- 29379363
TI  - Life forms, leaf size spectra, regeneration capacity and diversity of plant
      species grown in the Thandiani forests, district Abbottabad, Khyber Pakhtunkhwa,
      Pakistan.
AB  - The life form and leaf size spectra of plant species of the Thandiani forests,
      district Abbottabad, were studied during the summer of 2013. These forests host
      252 plant species of 97 families. Biological spectra showed that Hemicryptophytes
      (80 spp., 31.74%) were dominant followed by Megaphanerophytes (51 spp., 20.24%),
      Therophytes (49 spp., 19.44%) and Nanophanerophytes (45 spp., 17.86).
      Hemicryptophytes are the indicators of cold temperate vegetation. At the lower
      elevations, Megaphanerophytes and Nanophanerophytes were dominant which confirm
      trees as dominant habit form due to high soil depth, moisture and temperature
      factors. Data on Leaf spectra in the area showed that Microphyllous (88 spp.,
      34.92%) species were dominant followed by Leptophyllous (74 spp., 29.36%) and
      Nanophyllous (60 spp., 23.80%). The Microphyllous plants again are the indicator
      of cold temperate zone as the area is situated at an elevation of 1191-2626 m.
      Similarly, Nanophylls were dominant at lower elevations. Data on family
      importance values and diversity among various communities were also recorded.
      Life form and Leaf spectra studies could be used to understand the micro climatic
      variation of the region.

PMID- 29379364
TI  - DNA (cytosine-5)-methyltransferase 3B (DNMT 3B) polymorphism and risk of Down
      syndrome offspring.
AB  - Down syndrome (DS) is the most common form of human genetic mental retardation.
      Several polymorphisms in genes coding folic acid cycle enzymes have been
      associated to the risk of bearing a DS child; however, the results are
      controversial. S-adenosyl-l-methionine (SAM) is an important intermediate of
      folic acid pathway and acts as methyl donor and substrate for DNA (cytosine-5)
      methyltransferase 3B (DNMT3B - EC 2.1.1.37) de novo methylation processes during
      embryogenesis. Recent studies suggest that a functional polymorphism of DNMT 3B
      in maternal genotype may be associated with a decreased risk of having a DS
      child. We herein investigate the association of this polymorphism with the
      occurrence of DS in a Brazilian population. We have genotyped 111 mothers of DS
      infants (MDS) and 212 control mothers (CM) through PCR-RFLP. The observed
      genotypic frequencies were CC = 0.22; CT = 0.49 and TT = 0.29 in CM, and CC =
      0.30; CT = 0.52 and TT = 0.18 in MDS. Allelic frequencies were C = 0.47 and T =
      0.53 in CM and C = 0.56 and T = 0.44 in MDS. No deviation of HWE was observed,
      and both DNMT 3B rs2424913 genotype (chi2 = 4.53; DF = 1; P = 0.03) and allelic
      (chi2 = 4.90; DF = 1; P = 0.03) frequencies show significant differences between
      MDS and CM. The presence of the mutant DNMT 3B T allele decreases 30% the risk of
      bearing a DS child (OR = 0.69; 95% CI: 0.50-0.96; P = 0.03), and the risk is
      diminished up to 45% in association with the homozygous genotype (OR = 0.54; 95%
      CI: 0.31-0.96; P = 0.04). Our results suggest that women harboring the single
      nucleotide polymorphism DNMT 3B rs2424913 have a decreased risk of a DS
      pregnancy, and further studies are necessary to confirm this protective effect.

PMID- 29379365
TI  - Evaluation of effect of high frequency electromagnetic field on growth and
      antibiotic sensitivity of bacteria.
AB  - This study was aimed to evaluate the impact of high frequency electromagnetic
      fields (HF-EMF at 900 and 1800 MHz) on DNA, growth rate and antibiotic
      susceptibility of S. aureus, S. epidermidis, and P. aeruginosa. In this study,
      bacteria were exposed to 900 and 1800 MHz for 2 h and then inoculated to new
      medium when their growth rate and antibiotic susceptibility were evaluated.
      Results for the study of bacterial DNA unsuccessful to appearance any difference
      exposed and non-exposed S. aureus and S. epidermidis. Exposure of S. epidermidis
      and S. aureus to electromagnetic fields mostly produced no statistically
      significant decrease in bacterial growth, except for S. aureus when exposure to
      900 MHz at 12 h. Exposure of P. aeruginosa to electromagnetic fields at 900 MHz
      however, lead to a significant reduction in growth rate, while 1800 MHz had
      insignificant effect. With the exception of S. aureus, treated with amoxicillin
      (30 ug) and exposed to electromagnetic fields, radiation treatment had no
      significant effect on bacterial sensitivity to antibiotics.

PMID- 29379366
TI  - Rapid plant regeneration, validation of genetic integrity by ISSR markers and
      conservation of Reseda pentagyna an endemic plant growing in Saudi Arabia.
AB  - Reseda pentagyna is the only endemic species among the seven species of the
      genera Reseda found in Saudi Arabia. Probably no information is available on
      regeneration by conventional method of regeneration through seeds or cuttings.
      Therefore, alternative method of tissue culture was attempted to regenerate and
      multiply the plant. High shoot regeneration (14.44 shoots/explant) was obtained
      after four weeks, when shoot cuttings cultured on MS containing BA at 1.0 uM.
      Other cytokinins e.g., Kn, 2iP and TDZ found to be less effective in bud
      induction and shoot multiplication. Individual shoots were rooted on MS medium
      supplemented with various auxins at 0.5-5.0 uM concentrations. The IBA (1.5 uM)
      supplemented MS media induced maximum (83.3%) rooting. The plantlets were
      acclimatized and hardened under greenhouse conditions in plastic pots containing
      soil and farm yard manure with 95.0% success. The protocol developed would help
      to multiply the plant as well as conserve them in natural habitat. This can also
      be utilized to obtain active constituents for pharmaceutics and genetic
      manipulations.

PMID- 29379367
TI  - Biological activities of plant extracts from Ficus elastica and Selaginella
      vogelli: An antimalarial, antitrypanosomal and cytotoxity evaluation.
AB  - The cytotoxic, antiplasmodial, and antitrypanosomal activities of two medicinal
      plants traditionally used in Cameroon were evaluated. Wood of Ficus elastica
      Roxb. ex Hornem. aerial roots (Moraceae) and Selaginella vogelii Spring
      (Selaginellaceae) leaves were collected from two different sites in Cameroon. In
      vitro cell-growth inhibition activities were assessed on methanol extract of
      plant materials against Plasmodium falciparum strain 3D7 and Trypanosoma brucei
      brucei, as well as against HeLa human cervical carcinoma cells. Criteria for
      activity were an IC50 value < 10 MUg/mL. The extract of S. vogelii did not
      significantly reduce the viability of P. falciparum at a concentration of 25
      MUg/mL but dramatically affected the trypanosome growth with an IC50 of 2.4
      MUg/mL. In contrast, at the same concentration, the extract of F. elastica
      exhibited plasmodiacidal activity (IC50 value of 9.5 MUg/mL) and trypanocidal
      (IC50 value of 0.9 MUg/mL) activity. Both extracts presented low cytotoxic
      effects on HeLa cancer cell line. These results indicate that the selected
      medicinal plants could be further investigated for identifying compounds that may
      be responsible for the observed activities and that may represent new leads in
      parasitical drug discovery.

PMID- 29379368
TI  - Evaluation of genetic diversity of Panicum turgidum Forssk from Saudi Arabia.
AB  - The genetic diversity of 177 accessions of Panicum turgidum Forssk, representing
      ten populations collected from four geographical regions in Saudi Arabia, was
      analyzed using amplified fragment length polymorphism (AFLP) markers. A set of
      four primer-pairs with two/three selective nucleotides scored 836 AFLP amplified
      fragments (putative loci/genome landmarks), all of which were polymorphic.
      Populations collected from the southern region of the country showed the highest
      genetic diversity parameters, whereas those collected from the central regions
      showed the lowest values. Analysis of molecular variance (AMOVA) revealed that
      78% of the genetic variability was attributable to differences within
      populations. Pairwise values for population differentiation and genetic structure
      were statistically significant for all variances. The UPGMA dendrogram, validated
      by principal coordinate analysis-grouped accessions, corresponded to the
      geographical origin of the accessions. Mantel's test showed that there was a
      significant correlation between the genetic and geographical distances (r = 0.35,
      P < 0.04). In summary, the AFLP assay demonstrated the existence of substantial
      genetic variation in P. turgidum. The relationship between the genetic diversity
      and geographical source of P. turgidum populations of Saudi Arabia, as revealed
      through this comprehensive study, will enable effective resource management and
      restoration of new areas without compromising adaptation and genetic diversity.

PMID- 29379370
TI  - Nests of Marsh harrier (Circus aeruginosus L.) as refuges of potentially
      phytopathogenic and zoopathogenic fungi.
AB  - Birds' nests may be refuges for various species of fungi including that which are
      potentially phytopathogenic and zoopathogenic. Among the 2449 isolates of fungi
      obtained from nests of Marsh harriers 96.8% belonged to filamentous fungi. In
      total, 37 genera were identified from 63 fungi species. Within the mycobiotas of
      the examined nests populations of fungi which are potentially pathogenic for
      humans, homoiothermous animals and plants dominated. Among 63 species, 46 (72%)
      were potentially pathogenic fungi of which 18 species were potentially
      phytopathogenic and 32 species were pathogenic for homoiothermous animals. Inter
      alia species of fungi were found in the Marsh harriers nests: Aspergillus
      fumigatus, Aspergillus flavus, Scopulariopsis brevicaulis, Chrysosporium
      keratinophilum and Fusarium poae, Fusarium sporotrichioides. In terms of numbers,
      dominant in Marsh harrier nests were fungi pathogenic to birds, other
      homoiothermous animals and humans. On that basis it was concluded that Marsh
      harrier nests are both a source of fungal infections for that species and one of
      the links in the epidemiological cycle of opportunistic fungi for humans.

PMID- 29379371
TI  - Gender participation in sheep and goat farming in Najran, Southern Saudi Arabia.
AB  - Sheep and goat farming is a major source of income in the rural areas of Al
      Wadiah in Najran region of Southern Saudi Arabia. The study aims to identify the
      factors and parameters that influence gender participation in sheep and goat
      farming. Data were collected by interviewing 167 high school students, including
      70 male and 97 female students, in Al-Wadiah, by using the simple random sampling
      technique. Data were statistically analyzed to establish the relationship between
      gender and participation in sheep and goat farming. The study revealed
      significant differences between the two genders, for instance, male herders were
      more experienced, received more benefits, showed greater interest in discussions
      on topics related to sheep and goat farming, followed information from TV and
      radio, and received more services offered by veterinary clinics, which proved
      more beneficial for them. On the other hand, female herders received fewer
      services, and the veterinary clinics proved less beneficial for them. However,
      the correlation between the participation of both genders in sheep and goats
      management was non-significant toward the statement "feeling ashamed of
      participating in sheep and goat farming." Generally, sheep and goat rearing
      proves more beneficial for male participants than female participants, owing to
      their greater experience and interest in livestock farming. Moreover, they
      receive more benefits from TV, radio and veterinary clinics to maintain better
      health of their livestock. Both male and female herders contribute equally to
      sheep and goat farming by limiting the time spent on their daily routine. This
      study would enable policymakers and planners to develop more strategies and
      extension education programs to overcome the identified barriers and improve the
      livelihood of herders through their enhanced participation in remote areas.

PMID- 29379369
TI  - Chitosan treatment for skin ulcers associated with diabetes.
AB  - Infections, ulcerations, gangrene and, in severe cases, extremity amputation, are
      common complications among diabetic subjects. Various biomaterials have been
      utilized for the treatment of these lesions. Chitosan is an amino sugar with a
      low risk of toxicity and immune response. In this study, we evaluated chitosan
      topical gel and film treatments for subjects with diabetic ulcerations and wounds
      associated with diabetes mellitus. In a pre-experimental design, we described the
      result of chitosan gel and film treatment for wounds and skin ulcers among
      patients with long-standing diabetes mellitus. We studied 8 diabetic patients
      with wounds and skin ulcers (long duration and Wagner degree 1-2). Initially,
      most lesions had some degree of infection, tissue damage and ulceration. At the
      end of the treatment (topical chitosan) period, the infections were cured. All
      patients experienced a significant improvement in the initial injury and
      developed granulation tissue and a healthy skin cover. This report represents one
      of the few published clinical experience regarding the chitosan for the treatment
      of skin lesions among diabetic subjects. These results are relevant and promising
      for the treatment of this disease.

PMID- 29379372
TI  - Ovarian development and histological observations of threatened dwarf snakehead
      fish, Channa gachua (Hamilton, 1822).
AB  - Channa gachua were monthly sampled throughout a year and the histological
      analysis of their ovaries was done to determine the changes occurring in ovarian
      development. Based on histological examination of the ovaries, the oogenic
      process of C. gachua undergoes distinct cyclic and seasonal morphological
      changes. Five different developmental stages were identified under three major
      categories: pre-spawning (immature, maturing, mature), spawning (ripe-running)
      and post-spawning (spent). The peak spawning period of C. gachua was noticed
      during December - February. The gonadosomatic index (GSI) and ova diameter ranged
      from 0.79 to 3.61% and 543-1123 MUm respectively. The highest mean GSI (3.61 +/-
      0.16) and oocyte diameter (1123 +/- 55 MUm) were observed in December indicating
      that during this month the gonadal development reached maturity.

PMID- 29379373
TI  - Antibacterial activity of selected medicinal plants of northwest Pakistan
      traditionally used against mastitis in livestock.
AB  - The present study aimed to investigate the efficacy of traditionally used anti
      mastitis plants (Allium sativum, Bunium persicum, Oryza sativa and Triticum
      aestivum) in northwest Pakistan against bacterial pathogens. Selected plants were
      phytochemically screened for Alkaloids, Flavonoids, and Saponins and checked for
      in vitro antibacterial activity at concentration of 50 mg/ml against S. aureus,
      E. coli and K. pneumoniae by agar well diffusion method. Minimum inhibitory
      concentration and minimum bactericidal concentration was determined against
      multidrug resistant bacteria using tube dilution method. All extracts were found
      to significantly inhibit (p < 0.01, p < 0.05) the activity against bacterial
      strains examined. Among phytochemicals, alkaloids of all tested antimastitis
      plants produced significantly higher inhibition zones against bacteria. The
      minimum inhibitory concentration and minimum bactericidal concentration of
      phytochemicals and crude methanolic extracts against tested bacterial strains
      ranged between 12.5-50 mg/ml and 25-50 mg/ml, respectively. Medicinal plants
      traditionally used against mastitis are therapeutically active against bacterial
      pathogens. A. sativum and B. persicum were found to be potential candidate
      species for the development of novel veterinary drugs with low cost and fewer
      side effects.

PMID- 29379374
TI  - Comparative analysis of conventional and biological treatment in healing of bone
      disease.
AB  - The healing of Bone tissue consists of a complex process. Hence, we designed our
      study to evaluate chondrial diseases, which are as they have a very low healing
      capacity. Seventy two elderly osteoarthritis (OA) and 54-paediatric juvenile
      idiopathic arthritis (JIA) patients were included. The group was divided as 24 OA
      patients and 18 JIA patients in each group. Group I received Hyualuronic acid and
      glucocorticoides. Group II received platelet rich plasma and fibrin glue. Group
      III received PRP, fibrin glue, and MSC. 40 control patients received only PRP
      treatment. Out of 72 OA patients 35 (48.6%) male and 37 (51.4%) female with mean
      age of 48 +/- 6.5 years. 64 (88.9%) Patients had pain and swelling. 52 (72.2%)
      lacked flexibility. 42 (58.3%) had hypertrophy. 28 (38.9%) had less cartilage
      thickness. 34 (47.2%) were in grade 3, grade 2 has 28 (38.9%) and grade 1 has 10
      (13.9%) patients respectively. Among 54 JIA patients 28 (51.9%) male and 26
      (48.1%) female patients with mean, age 4.6 +/- 3.8 years. 39 (72.2%) had pain and
      swelling. 32 (59.3%) lacked flexibility. 29 (53.7%) children's had functional
      disability. Group I patients showed 30% improvement with no statistical
      significance (P < 0.21). Group II showed 45% improvement with statistical
      significance (P < 0.01). In Group III 80%, improvement was observed with
      statistical significance (P < 0.001). In 40 control patients, 60% improvement was
      observed. In conclusion, use of these MSC, PRP, and PPP are safe and less cost
      effective for treating OA and JIA.

PMID- 29379376
TI  - Citrinin detection by intensified fluorescence signal of a FRET-based
      immunosensor using magnetic/silica core-shell.
AB  - The specific immune-reaction between the anti-citrinin antibody immobilized on
      the surface of magnetic/silica core-shell (MSCS) and the citrinin-Rho123-BSA
      conjugate brings the Rho123 fluorophore as an acceptor and the QDs as a donor in
      close spatial proximity and causes FRET for occurring upon photo-excitation of
      the QDs. The novelties of this study include: (1) immobilization of the MSCS; (2)
      large amount of the immobilized QDs, and (3) immobilization of a large amount of
      Rho123 on the BSA macromolecule. Cd/Te QDs were synthesized by the simultaneous
      reduction of cadmium chloride and tellurium in the presence of sodium
      borohydride. Magnetic nanoparticles were synthesized using FeSO4 and FeCl3. The
      prepared magnetic nanoparticles shelled by silica using tetraethoxysilane in the
      presence of ammonia. Transmission electron microscopy (TEM) analysis was used for
      investigating shape and monodispersity of the nanoparticles. EDC/NHS was used as
      a cross linking agent for immobilization of the QDs, conjugation of citrinin to
      amino groups of BSA, labeling of BSA with Rho123 and also for immobilization of
      the amino-functionalized MSCS on the immobilized QDs. Immobilization of the anti
      citrinin antibody on the surface of the amino-functionalized MSCS was performed
      by Schiff-base mechanism. By using these three effective strategies, sensitivity
      of the designed nanobiosensor was incredibly enhanced as a very low limit of
      detection (up to 0.1 pM). The feasibility of this technique was tested by the
      detection of citrinin in the spiked human serum. Results showed that there was a
      linear correlation between the decreased fluorescence intensity of the Rho123 and
      increased fluorescence intensity of the QDs with increasing concentration of
      citrinin in the spiked samples in the range of 1-6 pM. According to obtained
      results, we conclude that this highly sensitive detection scheme is a easy, quick
      and impressive method that can be used in optical-based nanosensors.

PMID- 29379375
TI  - Susceptibility of mice strains to oxidative stress and neurotransmitter activity
      induced by Plasmodium berghei.
AB  - This study investigated the susceptibility of female C57Bl/6 and Swiss Albino
      mice to oxidative stress and neurotransmitters activity induced by Plasmodium
      berghei. On day 9 p.i. with P. berghei infected erythrocytes, the mice reduced in
      weight. This weight loss was markedly higher in SW mice and reached about -14%.
      Also, the infection was able to cause oxidative damage to the brain tissue.
      Catalase activity as well as glutathione, malondialdehyde and nitric oxide levels
      were different in the two mice strains. Moreover, the brain content of
      neurotransmitters, epinephrine, norepinephrine, dopamine and serotonin in mice
      brain was higher in SW mice than B6 mice. We concluded that, the strain of mice
      is one factor that could alter the response of mice to P. berghei infection.

PMID- 29379377
TI  - Metabolism of the spade-headed Amphisbaenian worm lizard, Diplometopon zarudnyi
      (Nikolsky, 1907), in Saudi Arabia (Reptilia: Trogonophidae).
AB  - The oxygen consumption rate [Formula: see text] and lactate production of the
      Amphisbaenian worm lizard Diplometopon zarudnyi were measured at temperatures
      ranging from 15  degrees C to 35  degrees C at 5  degrees C intervals. The
      [Formula: see text] was significantly different between resting and active states
      at any specified temperature, while the average value at the resting state
      generally rose with increased temperature from 15  degrees C (0.05 ml O2/g/h) to
      25  degrees C (0.111 ml O2/g/h). The aerobic respiration scopes at resting and
      active states were also significantly different. The highest Q10 values (3.24 and
      1.69) were obtained at 15  degrees C-20  degrees C and 30  degrees C-35  degrees
      C during resting and active states, respectively, with these values being
      significantly different. Lactate concentrations were significantly higher during
      active states than when resting, and the anaerobic scope was found to increase
      with increased temperature. There was a proportional increase in ATP molecules
      (MUmoles/g/2 min) during aerobic or anaerobic respiration, as well as in total
      metabolic scope, with increasing temperature, and the anaerobic scope showed
      significantly higher values than the aerobic scope, confirming the importance of
      anaerobic behavior for this species.

PMID- 29379378
TI  - Histopathological studies of experimental Aeromonas hydrophila infection in blue
      tilapia, Oreochromis aureus.
AB  - Blue tilapia, Oreochromis aureus, was experimentally infected with Aeromonas
      hydrophila, a bacterium that damages the gills, liver, and intestine, resulting
      in histopathological changes in the infected organs. Our histopathological study
      showed an aggregation of hemocytes with cell necrosis in gills; a massive
      aggregation of hemocytes and pyknotic nuclei in the hepatopancreas; and a lower
      rate of hemocyte aggregation in the digestive system of the infected fish.

PMID- 29379379
TI  - Cardamom (Elettaria cardamomum) perinatal exposure effects on the development,
      behavior and biochemical parameters in mice offspring.
AB  - Cardamom is a strong antioxidant plant, so it is called the queen of spices. In
      the present study, we explored the potentials of cardamom on developmental,
      learning ability and biochemical parameters of mice offspring. Thirty pregnant
      mice were allocated to three groups of ten animals in each. Groups Pi and SH
      received pilsbury's Diet containing 10 and 20% of cardamom (w/w) respectively,
      whereas Group I used as control. Cardomom was administered from the first day of
      pregnancy and was continued until post-natal day 15 (PD 15) and thereafter the
      mothers were switched to plain pilsbury's Diet. During the weaning period, three
      pups in each litter were color marked from the others, and were subjected to
      various tests (Physical assessment such body weight and eye opening and hair
      appearance; the neuromaturation of reflexes like righting, rotating, and cliff
      avoidance reflexes; learning ability and memory retention; estimation of
      monoamines neurotransmitters like dopamine and serotonin, non-enzymatic oxidative
      stress such as TBARS and GSH in forebrain at different ages of pups). The results
      indicated that the body weight gain was declining significantly. Hair appearance
      and eyes opening were delayed significantly. Righting, rotating, and cliff
      avoidance reflexes were delayed in treated animals. Exposure to cardamom led to
      enhance learning and memory retention as compared to control. Monoamines (DA, 5
      HT) and GSH were elevated, whereas TBARS was inhibited significantly. In
      conclusion, perinatal cardamom exposure enhanced learning and memory as compared
      to control. Cardamom and its benefit compounds were transported via placenta
      or/and milk during lactation. Cardamom needs more researches to investigate its
      benefits on other kinds of behavior.

PMID- 29379381
TI  - Malaysian Journal of Medical Sciences' Performance Status in 2016.
AB  - This editorial aims to report on the performance of the Malaysian Journal of
      Medical Sciences (MJMS) in the year 2016. The performance report is based on an
      analysis of the auto-generated data compiled from the ScholarOne ManuscriptsTM.
      It will specifically focus on the pattern of manuscript submission, geographical
      distribution of contributors, manuscript submission by month and the acceptance
      rejection rate of post-review manuscripts. It will also discuss the effects of
      the decision to raise the article acceptance standards. The MJMS would also like
      to share the news of its receipt of the 2016 Current Research in Malaysia (CREAM)
      award. This honour was bestowed upon us by the Ministry of Higher Education
      (MOHE) of Malaysia, on November 1, 2016.

PMID- 29379380
TI  - THE IMPACT OF CONSTRUCTION AND GENTRIFICATION ON AN OUTDOOR TRANS SEX WORK
      ENVIRONMENT: VIOLENCE, DISPLACEMENT AND POLICING.
AB  - The objective of this study was to investigate how environmental and structural
      changes to a trans outdoor work environment impacted sex workers in Vancouver,
      Canada. The issue of changes to the work area arose during qualitative interviews
      with 33 trans sex workers. In response, ethnographic walks that incorporated
      photography were undertaken with trans sex workers. Changes to the work
      environment were found to increase vulnerabilities to client violence, displace
      trans sex workers, and affect policing practices. Within a criminalized context,
      construction and gentrification enhanced vulnerabilities to violence and
      harassment from police and residents.

PMID- 29379382
TI  - Indicators for Medical Mistrust in Healthcare-A Review and Standpoint from
      Southeast Asia.
AB  - The relationship based on trust is exceptionally important in healthcare, where
      life or death and quality of health are major concerns. Relational crack
      jeopardises the provision of quality healthcare when trust is taken for granted.
      Trust is believed to be the vital key to minimise medical negligence, lawsuits
      and patient complaints towards healthcare providers while acting as an empowering
      agent to significant clinical outcomes. Trust is indispensable to healthcare.
      However, to identify its deterioration is not a simple feature. Moreover, lack of
      research and public dissemination complicate this topic further. Hence,
      understanding medical mistrust issues and their associated indicators is urgently
      needed to ensure the top-notch provision of healthcare. We employed narrative
      review methodology together with key terms matching for the selected electronic
      databases for this article. Our review concluded that an "Increasing number of
      medical litigations and complaints towards physicians", "Physicians' low mastery
      of interpersonal communication skill" and "Patients' demand, practice, and non
      disclosure of alternative treatments" are the possible indicators to predict
      mistrust. Efforts to restore and strengthen trust can only be made when these
      indicators are well understood firsthand.

PMID- 29379383
TI  - Comparison of Single-Shot Intrathecal Morphine Injection and Continuous Epidural
      Bupivacaine for Post-Operative Analgaesia after Elective Abdominal Hysterectomy.
AB  - Background: Abdominal hysterectomy (AH) is painful. The aim of this study was to
      compare intrathecal morphine (ITM) and epidural bupivacaine (EB) for their
      analgaesia effectiveness after this surgery. Methods: Thirty-two patients
      undergoing elective AH were randomised into Group ITM (ITM 0.2 mg + 2.5 mL 0.5%
      bupivacaine) (n = 16) and Group EB (0.25% bupivacaine bolus + continuous infusion
      of 0.1% bupivacaine-fentanyl 2 MUg/mL) (n = 16).The procedure was performed
      before induction, and all patients subsequently received standard general
      anaesthesia. Both groups were provided patient-controlled analgaesia morphine
      (PCAM) as a backup. Visual analogue scale (VAS) scores, total morphine
      consumption, hospital stay duration, early mobilisation time and first PCAM
      demand time were recorded. Results: The median VAS score was lower for ITM than
      for EB after the 1st hour [1.0 (IqR 1.0) versus 3.0 (IqR 3.0), P < 0.001], 8th
      hour [1.0 (IqR 1.0) versus 2.0 (IqR 1.0), P = 0.018] and 16th hour [1.0 (IqR1.0)
      versus (1.0 (IqR 1.0), P = 0.006]. The mean VAS score at the 4th hour was also
      lower for ITM [1.8 (SD 1.2) versus 2.9 (SD 1.4), P = 0.027]. Total morphine
      consumption [11.3 (SD 6.6) versus 16.5 (SD 4.8) mg, P = 0.016] and early
      mobilisation time [2.1 (SD 0.3) versus 2.6 (SD 0.9) days, P = 0.025] were also
      less for ITM. No significant differences were noted for other assessments.
      Conclusions: The VAS score was better for ITM than for EB at earlier hours after
      surgery. However, in terms of acceptable analgaesia (VAS <= 3), both techniques
      were comparable over 24 hours.

PMID- 29379384
TI  - Construction and Cloning of Reporter-Tagged Replicon cDNA for an In Vitro
      Replication Study of Murine Norovirus-1 (MNV-1).
AB  - Background: A norovirus maintains its viability, infectivity and virulence by its
      ability to replicate. However, the biological mechanisms of the process remain to
      be explored. In this work, the NanoLucTM Luciferase gene was used to develop a
      reporter-tagged replicon system to study norovirus replication. Methods: The
      NanoLucTM Luciferase reporter protein was engineered to be expressed as a fusion
      protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A
      (FMDV2A) sequence was inserted between the 3'end of the reporter gene and the VP2
      start sequence to allow co-translational 'cleavage' of fusion proteins during
      intracellular transcript expression. Amplification of the fusion gene was
      performed using a series of standard and overlapping polymerase chain reactions.
      The resulting amplicon was then cloned into three readily available backbones of
      MNV-1 cDNA clones. Results: Restriction enzyme analysis indicated that the
      NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA
      clone. The insertion was further confirmed by using DNA sequencing. Conclusion:
      NanoLucTM Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such
      clones can be exploited to develop robust experimental assays for in vitro
      assessments of viral RNA replication.

PMID- 29379385
TI  - Protection by Ethanolic Extract from Ulva lactuca L. against Acute Myocardial
      Infarction: Antioxidant and Antiapoptotic Activities.
AB  - Background: Reactive oxygen species (ROS) play a major role in myocardial damage
      during acute myocardial infarction (AMI). This study aimed to determine the
      antioxidant and antiapoptotic activities of an ethanolic extract from Ulva
      lactuca L. (EEUL) against AMI. Methods: Thirty-six male Wistar rats were divided
      into six groups: one control group and five treatment groups. Treatment group II
      was given 85 mg/kg body weight (BW) of isoproterenol (ISO). Group III, IV and V
      were given ISO and EEUL at 250, 500 and 750 mg/kg BW, respectively. Group VI were
      given 10 mg/kg BW of ISO and melatonin. EEUL and melatonin were orally
      administered for 28 days. ISO was injected subcutaneously on day 29 and 30 to
      chemically induce AMI. On day 31, blood was collected for antioxidant assay and
      heart tissues were collected for histological examination. Results: The activity
      of catalase (CAT), an endogenous antioxidant, in the EEUL-treatment groups was
      significantly increased compared to the ISO-treatment group (P < 0.001). The EEUL
      treatment groups showed significantly decreased expression of caspase-3 (P <
      0.001) and better myocardial tissue morphology. Conclusion: EEUL possibly
      protects against AMI because of its antioxidant and antiapoptotic properties.

PMID- 29379386
TI  - Low-dose Nicotine Exposure Induced the Oxidative Damage of Reproductive Organs
      and Altered the Sperm Characteristics of Adolescent Male Rats.
AB  - Background: Nicotine is a major toxic and hazardous component of cigarette smoke,
      and it has been widely used in nicotine replacement therapy (NRT). This study was
      aimed to investigate the effects of chronic low-dose nicotine on sperm
      characteristics and reproductive organ integrity in adolescent male Sprague
      Dawley rats. Methods: Twelve rats were equally divided into two groups. Group I
      received normal saline, and group II received 0.6 mg/kg body weight nicotine
      intraperitoneally for 28 consecutive days. At the end of the experimental period,
      sperm was collected for sperm characteristic evaluation, and the testes and
      prostate were isolated for biochemical and morphological analysis. The effects of
      nicotine on the body and reproductive organ weights of the animals were
      evaluated. Results: Chronic nicotine treatment significantly (P < 0.05) altered
      the sperm count, motility, viability, and morphology, and remarkably increased
      the malondialdehyde (P < 0.001) and advanced oxidation protein product (P < 0.05)
      levels in the testes and prostate of nicotine-treated group compared to control
      group. Moreover, nicotine caused a significant decrease (P < 0.05) in the
      superoxide dismutase activity of the testes. No significant differences were
      observed in the reduced glutathione level in both of the testes and prostate of
      nicotine group compared with control group. Nicotine also induced
      histopathological alteration in the testes. Conclusion: A low-dose nicotine
      exposure at 0.6 mg/kg caused detrimental effects on sperm characteristics and
      induced oxidative stress in the testes and prostate.

PMID- 29379387
TI  - Factors Affecting Visual Field Outcome Post-Surgery in Sellar Region Tumors:
      Retrospective Study.
AB  - Background: Despite the broad category of differentials for sellar region, most
      of them present with similar clinical signs and symptoms. Headache and visual
      disturbance are among the frequently seen as presenting symptom. Visual field
      (VF) assessment is one of the crucial component of neuroophtalmologic assessment
      and mean deviation (MD) value from automated perimetry allows quantification of
      the visual field defect. We formulated a study to look into the factors that
      affect the visual field outcome after surgery. Methods: All patients with sellar
      region tumor who has underwent surgery in Queen Elizabeth Hospital from July 2010
      to July 2016 were retrospectively analysed through hospital notes. VF assessment
      via Humphrey visual assessment for these patient pre and post-surgery were
      reviewed for MD value. Results: Eighty four patients were recruited and out of
      them, 151 eyes were taken into analysis after excluding eyes with missing data.
      Mean age of patients were 45.4 years with 70.2% of them were male. Visual
      disturbance is the commonest presenting symptom with mean duration of symptom
      prior to surgery is 9.7 months. Majority of them were pituitary adenomas (75%)
      followed by sellar meningioma (19%), craniopharyngioma (4.8%), and rathke cleft
      cyst (1.2%). 70.9% of patients showed improvement in VF based on MD outcome. Mean
      MD for pre surgery and post-surgery were -14.0 dB and -12.4 dB, respectively.
      Univariate analysis reveals younger age, female sex, shorter duration of symptom,
      pituitary adenoma, transsphenoidal approach, and transcranial approach favours
      improvement in VF. Multivariate analysis shows only shorter symptom duration,
      transphenoidal approach, and transcranial approach are significant for favourable
      VF outcome when other factors adjusted. Conclusion: Symptom duration and surgical
      approach were independent factors that affects the visual field after surgery in
      patients with sellar region tumors.

PMID- 29379388
TI  - Autologous Cranioplasty Post-Operative Surgical Site Infection: Does It Matter if
      the Bone Flaps were Stored and Handled Differently?

PMID- 29379389
TI  - Prevalence and Factors Associated with Tuberculosis Treatment Success among
      TB/HIV Co-Infection in North-East Malaysia.
AB  - Background: One of the six strategies developed by WHO, in order to stop
      Tuberculosis (TB) is addressing TB/HIV high-risk groups. This study aimed to
      determine the prevalence of successful TB treatment and factors associated with
      TB treatment success among TB/HIV co-infection patients in North-East Malaysia.
      Methods: A cross-sectional study was carried out in the a-year period from 2003
      to 2012 by reviewing TB/HIV records in all hospitals and health clinics. The
      outcome of interest was treatment success as defined by Ministry of Health (MOH)
      when the patients was cured or completed TB treatment. Results: Out of 1510 total
      TB/HIV co-infection cases, 27.9% (95% CI: 25.2, 30.6) of the patients were having
      treatment success. A majority of TB/HIV co-infection cases were male (91.1%).
      Fifty-eight percent the patients were drug addicts and 6% were having positive
      tuberculin tests. The multiple logistic regression revealed that male (OR: 0.39,
      95% CI: 0.22, 0.71) and positive tuberculin test result (OR: 2.61, 95% CI: 1.63,
      4.19) were significantly associated with the treatment success of TB/HIV co
      infection patients. Other factors such as age, comorbid, sputum smear and x-ray
      findings were not significantly factors in this study. Conclusion: Female
      patients and those with negative tuberculin test should be emphasised for
      successful tuberculosis treatment.

PMID- 29379390
TI  - Effects of Lifestyle Intervention towards Obesity and Blood Pressure among
      Housewives in Klang Valley: A Quasi-Experimental Study.
AB  - Background: The obesity rate in Malaysia is the highest in Asia. Half its
      population is obese or overweight. The present study aims to determine the
      effects of lifestyle intervention on weight loss and blood pressure among
      Malaysian overweight and obese housewives in Klang Valley. Methods: A quasi
      experimental study with 328 obese and overweight low socio- economic status
      housewives aged 18-59 years old who met the screening criteria participated in
      the study. They were recruited into an intervention group (N = 169) or control
      group (N = 159). The intervention group received a lifestyle intervention
      consisting of a diet, physical activity and self-monitoring behavior package. The
      control group (delayed intervention group) received a women's health seminar
      package. Both groups were followed up for six months. Weight, body mass index
      (BMI), and blood pressure were evaluated both pre- and post-intervention.
      Results: A total of 124 participants from the intervention group and 93
      participants from the control group completed the study. Mean weight loss was
      1.13 +/- 2.70 kg (P < 0.05) in the intervention group and 0.97 +/- 2.60 kg (P <
      0.05) in the control group. Systolic blood pressure (SBP) reductions in the
      intervention group were 5.84 +/- 18.10 mmHg (P < 0.05). The control group showed
      reduction in SBP 6.04 +/- 14.52 mmHg (P < 0.05). Both group had non-significant
      DBP reduction. Multivariate analysis via General Linear Model Repeated Measures
      observed no significant differences in terms of parameter changes with time in
      both groups for all parameters. Conclusions: The results indicate that the
      lifestyle interventions in this study resulted in modest weight loss and thus
      decreased BMI and blood pressure (SBP) within six months of intervention.

PMID- 29379391
TI  - Evaluating the Concept of Choice in Healthcare.
AB  - Choice is what we all want, as most would say. There is a growing cognisance that
      patients can and should play an important role in deciding their own care, in
      defining optimal care, and in improving healthcare delivery. Popular concepts
      such as patient-centred care, patient empowerment, and patients as partners,
      shared decision making, and informed choice illustrate the emancipation of
      patient. The paper describes that choice is not necessarily a good thing in
      health care; however, that does not rebut the significance of choice. In order to
      support the overall argument, the paper focuses on why patient choice is
      important, and in each discussion, this is disputed with counter-arguments to
      demonstrate that in fact, to an extent, choice is not necessarily a good thing in
      healthcare.

PMID- 29379392
TI  - Epilepsy Surgery in Hospital Universiti Sains Malaysia: Our Experiences since
      2004.
AB  - Epilepsy surgery has been performed by a few centres in Malaysia, including
      Hospital Universiti Sains Malaysia (HUSM). To date, a total of 15 patients have
      undergone epilepsy surgery in HUSM. The epilepsy surgery included anterior
      temporal lobectomy (ATL) with amygdalohippocampectomy (AH) and Vagal nerve
      stimulation (VNS). The surgical outcomes of the patients were assessed using the
      International League Against Epilepsy (ILAE) outcome scale. The ILAE scores for
      patients who underwent ATL with AH were comparatively better than those who
      underwent VNS. One of the patient who underwent ATL with AH and frontal
      lesionectomy was found to have psychosis during follow up. Epilepsy surgery has
      proven to be an important treatment for medically resistant epilepsy. Thus it is
      important to raise public awareness regarding epilepsy and its treatment.

PMID- 29379393
TI  - A Rare Presentation of Tubercular Meningitis as Persistent Neutrophilic
      Meningitis.
AB  - Persistent neutrophilic meningitis is an atypical form of chronic meningitis
      defined as clinical meningitis with a cerebrospinal fluid (CSF) analysis
      suggestive of neutrophilic pleocytosis that persists for more than one week
      despite giving empirical antimicrobial therapy. The predominant presentation of
      tubercular meningitis is with CSF lymphocytic pleocytosis and even if early phase
      of the disease presents with neutrophilic pleocytosis, no persistence is usually
      observed for more than one week. We hereby report the case of an immunocompetent
      man aged 25 years with tubercular meningitis manifesting as persistent
      neutrophilic meningitis which is very rare as an entity in tubercular meningitis
      (TBM). Patient was started on anti-tubercular therapy based on the granulomas in
      magnetic resonance imaging (MRI) of the brain after which there was a reduction
      in total cell count in CSF but persisting neutrophilic predominance. Patient
      improved clinically and was given a full course of anti-tubercular treatment
      (ATT) thereafter.

PMID- 29379394
TI  - Embolisation of External Jugular Vein Aneurysm: A Case Report.
AB  - Introduction: Venous aneurysms are not as common as their arterial counterpart.
      The choice of management is debatable. Case Report: We present the case of a
      teenage boy with left external jugular vein aneurysm treated by endovascular
      technique. Embolisation was done using pushable microcoils with access via the
      femoral vein and direct puncture. Conclusion: This form of treatment provides a
      less-invasive option with a more concrete evaluation of the venous abnormality
      and its drainage during venous aneurysm occlusion.

PMID- 29379395
TI  - The Efficacy of Intra-Operative Ultrasound for Tumour Resection Compared to Post
      Operative MRI Brain.

PMID- 29379396
TI  - What goes up must come down: homeostatic synaptic plasticity strategies in
      neurological disease.
AB  - Brain activity levels are tightly regulated to minimize imbalances in activity
      state. Deviations from the normal range of activity are deleterious and often
      associated with neurological disorders. To maintain optimal levels of activity,
      regulatory mechanisms termed homeostatic synaptic plasticity establish desired
      'set points' for neural activity, monitor the network for deviations from the set
      point and initiate compensatory responses to return activity to the appropriate
      level that permits physiological function [1,2]. We speculate that impaired
      homeostatic control may contribute to the etiology of various neurological
      disorders including epilepsy and Alzheimer's disease, two disorders that exhibit
      hyperexcitability as a key feature during pathogenesis. Here, we will focus on
      recent progress in developing homeostatic regulation of neural activity as a
      therapeutic tool.

PMID- 29379397
TI  - Comorbid autism spectrum disorder and anxiety disorders: a brief review.
AB  - Appearing in 40% of the cases of autism spectrum disorder (ASD), comorbid anxiety
      presents unique challenges for practitioners by amplifying problem behaviors such
      as social skills deficits, resistance to change and repetitive behaviors.
      Furthermore, comorbid ASD/anxiety strains familial relationships and increases
      parental stress. Research indicates that the neurobiological interactions between
      anxiety and ASD require comprehensive assessment approaches, modified cognitive
      behavioral therapy and carefully managed pharmacological interventions. Meta
      analyses indicate that cognitive behavioral therapy with exposure is an effective
      treatment option when adequately accounting for social, familial and cognitive
      variables. The purpose of this focused review is to update readers on the latest
      research advances in comorbid ASD and anxiety, including prevalence, assessment,
      psychosocial and pharmacological treatment.

PMID- 29379399
TI  - Sean C. Glasgow, MD, FACS, FASCRS.

PMID- 29379398
TI  - Radiotherapy setup displacements in breast cancer patients: 3D surface imaging
      experience.
AB  - Aim: In this study, we intend to compare two different setup procedures for
      female breast cancer patients. Background: Imaging in radiotherapy provides a
      precise localization of the tumour, increasing the accuracy of the treatment
      delivery in breast cancer. Materials and methods: Twenty breast cancer patients
      who underwent whole breast radiotherapy (WBRT) were selected for this study.
      Patients were divided into two groups of ten. Group one (G1) was positioned by
      tattoos and then the patient positioning was adjusted with the aid of AlignRT
      (Vision RT, London, UK). In group two (G2), patients were positioned only by
      tattoos. For both groups, the first 15 fractions were analyzed, a daily
      kilovoltage (kV) cone beam computed tomography (CBCT) image was made and then the
      rotational and translational displacements and, posteriorly, the systematic
      (Sigma) and random (sigma) errors were analyzed. Results: The comparison of CBCT
      displacements for the two groups showed a statistically significant difference in
      the translational left-right (LR) direction (rho = 0.03), considering that the
      procedure with AlignRT system has smaller lateral displacements. The results of
      systematic (Sigma) and random (sigma) errors showed that for translational
      displacements the group positioned only by tattoos (G2) demonstrated higher
      values of errors when compared with the group positioned with the aid of AlignRT
      (G1). Conclusions: AlignRT could help the positioning of breast cancer patients;
      however, it should be used with another imaging method.

PMID- 29379400
TI  - Colorectal Trauma.

PMID- 29379401
TI  - Historical Perspectives on Colorectal Trauma Management.
AB  - The authors discuss the history and evolution of management of traumatic wounds
      to the colon and rectum, summarizing early management parallel with the history
      of armed conflict followed by the increase in research and management interest by
      civilian centers in the post-Vietnam era. They explore the strong opinions of the
      early thought-leaders such as DeBakey and Ogilvie, detailing factors that may
      have impacted their views. The current literature on optimal management of both
      colon and rectal trauma is reviewed, including the contentious debate over which
      patients may benefit from diversion. Current organ injury staging and clinical
      practice guidelines are also reviewed, as well as lessons learned by the U.S.
      military in recent conflicts in Iraq and Afghanistan. Understanding of the
      evolution of colon and rectal trauma management, as well as the current
      literature, will help surgeons in their decision-making and management of these
      challenging injuries.

PMID- 29379402
TI  - Colon Trauma: Evidence-Based Practices.
AB  - Colon injury is not uncommon and occurs in about a half of patients with
      penetrating hollow viscus injuries. Despite major advances in the operative
      management of penetrating colon wounds, there remains discussion regarding the
      appropriate treatment of destructive colon injuries, with a significant amount of
      scientific evidence supporting segmental resection with primary anastomosis in
      most patients without comorbidities or large transfusion requirement. Although
      literature is sparse concerning the management of blunt colon injuries, some
      studies have shown operative decision based on an algorithm originally defined
      for penetrating wounds should be considered in blunt colon injuries. The optimal
      management of colonic injuries in patients requiring damage control surgery (DCS)
      also remains controversial. Studies have recently reported that there is no
      increased risk compared with patients treated without DCS if fascial closure is
      completed on the first reoperation, or that a management algorithm for
      penetrating colon wounds is probably efficacious for colon injuries in the
      setting of DCS as well.

PMID- 29379403
TI  - Rectal Trauma: Evidence-Based Practices.
AB  - The management of rectal trauma has often been lumped in with colon trauma when,
      in fact, it is a unique entity. The anatomic nature of the rectum (with its intra
      and extraperitoneal segments) lends itself to unique circumstances when it comes
      to management and treatment. From the four Ds (debridement, drainage, diversion,
      and distal irrigation), the management of rectal trauma has made some strides in
      light of the experiences coming out of the recent conflicts overseas as well as
      some rethinking of dogma. This article will serve to review the anatomy and types
      of injuries associated with rectal trauma. A treatment algorithm will also be
      presented based on our current literature review. We will also address
      controversial points and attempt to give our opinion in an effort to provide an
      update on an age-old problem.

PMID- 29379404
TI  - Anal and Perineal Injuries.
AB  - With increased use of explosive devices in warfare, anal trauma is often seen
      coupled with more complex pelviperineal injury. While the associated mortality is
      high, casualties that survive are often left with disabling fecal incontinence
      from damage to the anosphincteric complex. After resolution of the acute insult,
      the initial evaluation mandates a thorough physical exam, including endoscopic
      evaluation with rigid proctoscopy and flexible sigmoidoscopy, as well as
      adjunctive testing, specifically anal manometry and endoanal ultrasound. First
      line therapy favors bulking agents and antidiarrheals, in conjunction with
      biofeedback, due to a minimal risk profile. Surgical options range from direct
      sphincter repairs to complex anosphincteric reconstruction with widely variable
      results. Most recently, burgeoning therapies in the treatment of fecal
      incontinence, including sacral nerve stimulation and magnetic anal sphincters,
      offer excellent alternatives with promising long-term outcomes. In summation, the
      goal of all interventions is the re-establishment of bowel continence, but, in
      its absence, permanent fecal diversion for devastating fecal incontinence is a
      reasonable option with excellent patient satisfaction scores.

PMID- 29379405
TI  - The Evolution of Damage Control in Concept and Practice.
AB  - Damage control surgery (DCS) began as an adjunct approach to hemorrhage control,
      seeking to facilitate the body's innate clotting ability when direct repair or
      ligation was impossible, but it has since become a valuable instrument for a
      broader collection of critically ill surgical patients in whom metabolic
      dysfunction is the more immediate threat to life than imminent exsanguination.
      Modern damage control is a strategy that combines the principles of DCS with
      those of damage control resuscitation. When used correctly, damage control may
      improve survival in previously unsalvageable patients; when used incorrectly, it
      can subject patients to imprudent risk and contribute to morbidity. This review
      discusses the evolution of damage control in both concept and practice,
      summarizing available literature and experience to guide patient selection,
      medical decision-making, and strategy implementation throughout the preoperative,
      intraoperative, and early postoperative periods.

PMID- 29379406
TI  - Management of Destructive Colon Injuries after Damage Control Surgery.
AB  - After the World War II, fecal diversion became the standard of care for colon
      injuries, although medical, logistic, and technical advancements have challenged
      this approach. Damage control surgery serves to temporize immediately life
      threatening conditions, and definitive management of destructive colon injuries
      is delayed until after appropriate resuscitation. The bowel can be left in
      discontinuity for up to 3 days before edema ensues, but the optimal repair window
      remains within 12 to 48 hours. Delayed anastomosis performed at the take-back
      operation or stoma formation has been reported with variable results. Studies
      have revealed good outcomes in those undergoing anastomosis after damage control
      surgery; however, they point to a subgroup of trauma patients considered to be
      "high risk" that may benefit from fecal diversion. Risk factors influencing
      morbidity and mortality rates include hypotension, massive transfusion, the
      degree of intra-abdominal contamination, associated organ injuries, shock, left
      sided colon injury, and multiple comorbid conditions. Patients who are not
      suitable for anastomosis by 36 hours after damage control may be best managed
      with a diverting stoma. Failures are more likely related to ongoing instability,
      and the management strategy of colorectal injury should be based mainly on the
      patient's overall condition.

PMID- 29379407
TI  - Colonoscopic Perforations.
AB  - Colonoscopy is the gold standard for colon cancer screening. It has led to a
      decrease in the incidence of colorectal cancer mortality. Colon perforation is a
      feared complication of this procedure with high morbidity and substantial
      mortality. Due to the high volume of colonoscopies performed, the absolute number
      of colonoscopic perforations is relatively high. It leads to a substantial cost
      to the patient and the health system. Understanding the mechanisms and the risk
      factors may help in preventing perforation. Traditionally, a laparotomy with
      creation of a stoma was used to address this complication. However, minimally
      invasive techniques such as laparoscopy and endoluminal repairs are being used
      more commonly now. More surgeons are favoring primary anastomosis (with or
      without a diverting loop ileostomy) than a Hartmann procedure.

PMID- 29379408
TI  - The Application of Functional Imaging in the Diagnosis of Tumors.

PMID- 29379409
TI  - Parkinson's Disease Skin Fibroblasts Display Signature Alterations in Growth,
      Redox Homeostasis, Mitochondrial Function, and Autophagy.
AB  - The discovery of biomarkers for Parkinson's disease (PD) is challenging due to
      the heterogeneous nature of this disorder, and a poor correlation between the
      underlying pathology and the clinically expressed phenotype. An ideal biomarker
      would inform on PD-relevant pathological changes via an easily assayed biological
      characteristic, which reliably tracks clinical symptoms. Human dermal (skin)
      fibroblasts are accessible peripheral cells that constitute a patient-specific
      system, which potentially recapitulates the PD chronological and epigenetic aging
      history. Here, we compared primary skin fibroblasts obtained from individuals
      diagnosed with late-onset sporadic PD, and healthy age-matched controls. These
      fibroblasts were studied from fundamental viewpoints of growth and morphology, as
      well as redox, mitochondrial, and autophagic function. It was observed that
      fibroblasts from PD subjects had higher growth rates, and appeared distinctly
      different in terms of morphology and spatial organization in culture, compared to
      control cells. It was also found that the PD fibroblasts exhibited significantly
      compromised mitochondrial structure and function when assessed via morphological
      and oxidative phosphorylation assays. Additionally, a striking increase in
      baseline macroautophagy levels was seen in cells from PD subjects. Exposure of
      the skin fibroblasts to physiologically relevant stress, specifically ultraviolet
      irradiation (UVA), further exaggerated the autophagic dysfunction in the PD
      cells. Moreover, the PD fibroblasts accumulated higher levels of reactive oxygen
      species (ROS) coupled with lower cell viability upon UVA treatment. In essence,
      these studies highlight primary skin fibroblasts as a patient-relevant model that
      captures fundamental PD molecular mechanisms, and supports their potential
      utility to develop diagnostic and prognostic biomarkers for the disease.

PMID- 29379410
TI  - No Effects of Stimulating the Left Ventrolateral Prefrontal Cortex with tDCS on
      Verbal Working Memory Updating.
AB  - The effects of transcranial direct current stimulation (tDCS) on dorsolateral
      prefrontal cortex functions, such as working memory (WM), have been examined in a
      number of studies. However, much less is known about the behavioral effects of
      tDCS over other important WM-related brain regions, such as the ventrolateral
      prefrontal cortex (VLPFC). In a counterbalanced within-subjects design with 33
      young healthy participants, we examined whether online and offline single-session
      tDCS over VLPFC affects WM updating performance as measured by a digit 3-back
      task. We compared three conditions: anodal, cathodal and sham. We observed no
      significant tDCS effects on participants' accuracy or reaction times during or
      after the stimulation. Neither did we find any differences between anodal and
      cathodal stimulation. Largely similar results were obtained when comparing
      subgroups of high- and low-performing participants. Possible reasons for the lack
      of effects, including individual differences in responsiveness to tDCS, features
      of montage, task and sample characteristics, and the role of VLPFC in WM, are
      discussed.

PMID- 29379411
TI  - Stable Sparse Classifiers Identify qEEG Signatures that Predict Learning
      Disabilities (NOS) Severity.
AB  - In this paper, we present a novel methodology to solve the classification
      problem, based on sparse (data-driven) regressions, combined with techniques for
      ensuring stability, especially useful for high-dimensional datasets and small
      samples number. The sensitivity and specificity of the classifiers are assessed
      by a stable ROC procedure, which uses a non-parametric algorithm for estimating
      the area under the ROC curve. This method allows assessing the performance of the
      classification by the ROC technique, when more than two groups are involved in
      the classification problem, i.e., when the gold standard is not binary. We apply
      this methodology to the EEG spectral signatures to find biomarkers that allow
      discriminating between (and predicting pertinence to) different subgroups of
      children diagnosed as Not Otherwise Specified Learning Disabilities (LD-NOS)
      disorder. Children with LD-NOS have notable learning difficulties, which affect
      education but are not able to be put into some specific category as reading
      (Dyslexia), Mathematics (Dyscalculia), or Writing (Dysgraphia). By using the EEG
      spectra, we aim to identify EEG patterns that may be related to specific learning
      disabilities in an individual case. This could be useful to develop subject-based
      methods of therapy, based on information provided by the EEG. Here we study 85 LD
      NOS children, divided in three subgroups previously selected by a clustering
      technique over the scores of cognitive tests. The classification equation
      produced stable marginal areas under the ROC of 0.71 for discrimination between
      Group 1 vs. Group 2; 0.91 for Group 1 vs. Group 3; and 0.75 for Group 2 vs.
      Group1. A discussion of the EEG characteristics of each group related to the
      cognitive scores is also presented.

PMID- 29379412
TI  - Functional Characterization and Signaling Systems of Corazonin and Red Pigment
      Concentrating Hormone in the Green Shore Crab, Carcinus maenas.
AB  - Neuropeptides play a central role as neurotransmitters, neuromodulators and
      hormones in orchestrating arthropod physiology. The post-genomic surge in
      identified neuropeptides and their putative receptors has not been matched by
      functional characterization of ligand-receptor pairs. Indeed, until very recently
      no G protein-coupled receptors (GPCRs) had been functionally defined in any
      crustacean. Here we explore the structurally-related, functionally-diverse
      gonadotropin-releasing hormone paralogs, corazonin (CRZ) and red-pigment
      concentrating hormone (RPCH) and their G-protein coupled receptors (GPCRs) in the
      crab, Carcinus maenas. Using aequorin luminescence to measure in vitro Ca2+
      mobilization we demonstrated receptor-ligand pairings of CRZ and RPCH. CRZR
      activated cell signaling in a dose-dependent manner (EC50 0.75 nM) and
      comparative studies with insect CRZ peptides suggest that the C-terminus of this
      peptide is important in receptor-ligand interaction. RPCH interacted with RPCHR
      with extremely high sensitivity (EC50 20 pM). Neither receptor bound GnRH, nor
      the AKH/CRZ-related peptide. Transcript distributions of both receptors indicate
      that CRZR expression was, unexpectedly, restricted to the Y-organs (YO).
      Application of CRZ peptide to YO had no effect on ecdysteroid biosynthesis,
      excepting a modest stimulation in early post-molt. CRZ had no effect on heart
      activity, blood glucose levels, lipid mobilization or pigment distribution in
      chromatophores, a scenario that reflected the distribution of its mRNA. Apart
      from the well-known activity of RPCH as a chromatophorotropin, it also indirectly
      elicited hyperglycemia (which was eyestalk-dependent). RPCHR mRNA was also
      expressed in the ovary, indicating possible roles in reproduction. The anatomy of
      CRZ and RPCH neurons in the nervous system is described in detail by
      immunohistochemistry and in situ hybridization. Each peptide has extensive but
      non-overlapping distribution in the CNS, and neuroanatomy suggests that both are
      possibly released from the post-commissural organs. This study is one of the
      first to deorphanize a GPCR in a crustacean and to provide evidence for hitherto
      unknown and diverse functions of these evolutionarily-related neuropeptides.

PMID- 29379413
TI  - Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator
      Cpeb1.
AB  - Adult mammalian central nervous system (CNS) neurons are unable to regenerate
      following axonal injury, leading to permanent functional impairments. Yet, the
      reasons underlying this regeneration failure are not fully understood. Here, we
      studied the transcriptome and translatome shortly after spinal cord injury.
      Profiling of the total and ribosome-bound RNA in injured and naive spinal cords
      identified a substantial post-transcriptional regulation of gene expression. In
      particular, transcripts associated with nervous system development were down
      regulated in the total RNA fraction while remaining stably loaded onto ribosomes.
      Interestingly, motif association analysis of post-transcriptionally regulated
      transcripts identified the cytoplasmic polyadenylation element (CPE) as enriched
      in a subset of these transcripts that was more resistant to injury-induced
      reduction at the transcriptome level. Modulation of these transcripts by
      overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS
      neurons promoted axonal regeneration following injury. Our study uncovered a
      global evolutionarily conserved post-transcriptional mechanism enhancing
      regeneration of injured CNS axons.

PMID- 29379414
TI  - Brain Lateralization in Mice Is Associated with Zinc Signaling and Altered in
      Prenatal Zinc Deficient Mice That Display Features of Autism Spectrum Disorder.
AB  - A number of studies have reported changes in the hemispheric dominance in autism
      spectrum disorder (ASD) patients on functional, biochemical, and morphological
      level. Since asymmetry of the brain is also found in many vertebrates, we
      analyzed whether prenatal zinc deficient (PZD) mice, a mouse model with ASD like
      behavior, show alterations regarding brain lateralization on molecular and
      behavioral level. Our results show that hemisphere-specific expression of marker
      genes is abolished in PZD mice on mRNA and protein level. Using magnetic
      resonance imaging, we found an increased striatal volume in PZD mice with no
      change in total brain volume. Moreover, behavioral patterns associated with
      striatal lateralization are altered and the lateralized expression of dopamine
      receptor 1 (DR1) in the striatum of PZD mice was changed. We conclude that zinc
      signaling during brain development has a critical role in the establishment of
      brain lateralization in mice.

PMID- 29379415
TI  - Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient
      Specific Novel Mutation.
AB  - X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations
      in the gene encoding retinoschisin (RS1), which leads to a significant proportion
      of visual impairment and blindness. To develop personalized genome editing based
      gene therapy, knock-in animal disease models that have the exact mutation
      identified in the patients is extremely crucial, and that the way which genome
      editing in knock-in animals could be easily transferred to the patients. Here we
      recruited a family diagnosed with XLRS and identified the causative mutation
      (RS1, p.Y65X), then a knock-in mouse model harboring this disease-causative
      mutation was generated via TALEN (transcription activator-like effector
      nucleases). We found that the b-wave amplitude of the ERG of the RS1-KI mice was
      significantly decreased. Moreover, we observed that the structure of retina in
      RS1-KI mice has become disordered, including the disarray of inner nuclear layer
      and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments
      of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI)
      harboring patient-specific mutation will be valuable for development of treatment
      via genome editing mediated gene correction.

PMID- 29379417
TI  - Genome-Edited, TH-expressing Neuroblastoma Cells as a Disease Model for Dopamine
      Related Disorders: A Proof-of-Concept Study on DJ-1-deficient Parkinsonism.
AB  - Impairment of the dopaminergic (DA) system is a common cause of several movement
      disorders including Parkinson's disease (PD), however, little is known about the
      underlying disease mechanisms. The recent development of stem-cell-based
      protocols for the generation of DA neurons partially solved this issue, however,
      this technology is costly and time-consuming. Commonly used cell lines, i.e.,
      neuroblastoma (SHSY5Y) and PC12 cells are still widely used to investigate PD and
      significantly contributed to our understanding of mechanisms involved in
      development of the disease. However, they either do not express DA at all or
      require additional, only partially efficient differentiations in order to produce
      DA. Here we generated and characterized transgenic SH-SY5Y cells, ectopically
      expressing tyrosine hydroxylase (SHTH+), that can be used as a homogenous, DA
      producing model to study alterations in DA metabolism and oxidative stress. We
      demonstrated that SHTH+ produce high levels of DA, 3,4-dihydroxyphenylacetic acid
      (DOPAC), and homovanillic acid (HVA) making this model suitable to investigate
      not only alterations in DA synthesis but also its turnover. We also provide
      evidence for the presence of other enzymes involved in DA synthesis and its
      turnover in these cells. Finally, we showed that these cells can easily be
      genetically modified using CRISPR/Cas9 technology in order to study genetically
      defined forms of movement disorders using DJ1-linked PD as a model.

PMID- 29379416
TI  - Molecular Signatures Underlying Synaptic Vesicle Cargo Retrieval.
AB  - Efficient retrieval of the synaptic vesicle (SV) membrane from the presynaptic
      plasma membrane, a process called endocytosis, is crucial for the fidelity of
      neurotransmission, particularly during sustained neural activity. Although
      multiple modes of endocytosis have been identified, it is clear that the
      efficient retrieval of the major SV cargos into newly formed SVs during any of
      these modes is fundamental for synaptic transmission. It is currently believed
      that SVs are eventually reformed via a clathrin-dependent pathway. Various
      adaptor proteins recognize SV cargos and link them to clathrin, ensuring the
      efficient retrieval of the cargos into newly formed SVs. Here, we summarize our
      current knowledge of the molecular signatures within individual SV cargos that
      underlie efficient retrieval into SV membranes, as well as discuss possible
      contributions of the mechanisms under physiological conditions.

PMID- 29379418
TI  - Adenosine A1 Receptor-Mediated Attenuation of Reciprocal Dendro-Dendritic
      Inhibition in the Mouse Olfactory Bulb.
AB  - It is well described that A1 adenosine receptors inhibit synaptic transmission at
      excitatory synapses in the brain, but the effect of adenosine on reciprocal
      synapses has not been studied so far. In the olfactory bulb, the majority of
      synapses are reciprocal dendro-dendritic synapses mediating recurrent inhibition.
      We studied the effect of A1 receptor activation on recurrent dendro-dendritic
      inhibition in mitral cells using whole-cell patch-clamp recordings. Adenosine
      reduced dendro-dendritic inhibition in wild-type, but not in A1 receptor knock
      out mice. Both NMDA receptor-mediated and AMPA receptor-mediated dendro-dendritic
      inhibition were attenuated by adenosine, indicating that reciprocal synapses
      between mitral cells and granule cells as well as parvalbumin interneurons were
      targeted by A1 receptors. Adenosine reduced glutamatergic self-excitation and
      inhibited N-type and P/Q-type calcium currents, but not L-type calcium currents
      in mitral cells. Attenuated glutamate release, due to A1 receptor-mediated
      calcium channel inhibition, resulted in impaired dendro-dendritic inhibition. In
      behavioral tests we tested the ability of wild-type and A1 receptor knock-out
      mice to find a hidden piece of food. Knock-out mice were significantly faster in
      locating the food. Our results indicate that A1 adenosine receptors attenuates
      dendro-dendritic reciprocal inhibition and suggest that they affect odor
      information processing.

PMID- 29379419
TI  - Reductions in Corpus Callosum Volume Partially Mediate Effects of Prenatal
      Alcohol Exposure on IQ.
AB  - Disproportionate volume reductions in the basal ganglia, corpus callosum (CC) and
      hippocampus have been reported in children with prenatal alcohol exposure (PAE).
      However, few studies have investigated these reductions in high prevalence
      communities, such as the Western Cape Province of South Africa, and only one
      study made use of manual tracing, the gold standard of volumetric analysis. The
      present study examined the effects of PAE on subcortical neuroanatomy using
      manual tracing and the relation of volumetric reductions in these regions to IQ
      and performance on the California Verbal Learning Test-Children's Version (CVLT
      C), a list learning task sensitive to PAE. High-resolution T1-weighted images
      were acquired, using a sequence optimized for morphometric neuroanatomical
      analysis, on a Siemens 3T Allegra MRI scanner from 71 right-handed, 9- to 11-year
      old children [9 fetal alcohol syndrome (FAS), 19 partial FAS (PFAS), 24 non
      syndromal heavily exposed (HE) and 19 non-exposed controls]. Frequency of
      maternal drinking was ascertained prospectively during pregnancy using timeline
      follow-back interviews. PAE was examined in relation to volumes of the CC and
      left and right caudate nuclei, nucleus accumbens and hippocampi. All structures
      were manually traced using Multitracer. Higher levels of PAE were associated with
      reductions in CC volume after adjustment for TIV. Although the effect of PAE on
      CC was confounded with smoking and lead exposure, additional analyses showed that
      it was not accounted for by these exposures. Amongst dysmorphic children, smaller
      CC was associated with poorer IQ and CVLT-C scores and statistically mediated the
      effect of PAE on IQ. In addition, higher levels of PAE were associated with
      bilateral volume reductions in caudate nuclei and hippocampi, effects that
      remained significant after control for TIV, child sex and age, socioeconomic
      status, maternal smoking during pregnancy, and childhood lead exposure. These
      data confirm previous findings showing that PAE is associated with decreases in
      subcortical volumes and is the first study to show that decreases in callosal
      volume may play a role in fetal alcohol-related impairment in cognitive function
      seen in childhood.

PMID- 29379420
TI  - Differential Influence of Early Life and Adult Stress on Urogenital Sensitivity
      and Function in Male Mice.
AB  - Experiences of adverse childhood events have been associated with improper output
      of the hypothalamic-pituitary-adrenal (HPA) axis in adulthood, as well as
      development of comorbid functional pain disorders. Symptoms of chronic
      prostatitis/chronic pelvic pain syndrome frequently overlap with those of
      interstitial cystitis/painful bladder syndrome and symptom severity is often
      triggered by stress. The objective of this study was to investigate the influence
      early life stress and acute adult stress on (1) perigenital sensitivity, (2)
      micturition, (3) anhedonia, and (4) HPA axis regulation and output in male
      C56Bl/6 mice. Neonatal maternal separation (NMS) was performed for 3 h a day from
      postnatal day 1 to 21 and naive pups remained unhandled during this time. As
      adults, male mice were tested for referred prostate sensitivity and micturition
      patterning prior to and 1 and 8 days after exposure to 1 h of water avoidance
      stress (WAS). Following testing, prostate and bladder tissues were used for mast
      cell and Western blot analysis and RT-PCR was performed on mRNA from
      hypothalamus, amygdala, and hippocampus. Serum corticosterone (CORT) was also
      measured by enzyme-linked immunosorbent assay (ELISA). A significant increase in
      perigenital sensitivity and micturition frequency was observed in NMS mice and
      these measures were exacerbated by WAS exposure. Exposure to NMS significantly
      increased mast cell degranulation in both the bladder and prostate. Mast cell
      degranulation was also increased in naive prostate tissue following WAS exposure.
      Cytokine mRNA levels were influenced by both NMS and WAS exposure, though WAS had
      a larger impact on central gene expression. Protein levels of CRF1 were
      differentially regulated by NMS and WAS in the bladder and prostate and serum
      CORT levels were significantly diminished following stress exposure. Taken
      together, these data suggest that NMS results in neurogenic inflammation and
      hypersensitivity within the urogenital organs, coupled with diminished gene
      expression and output from the HPA axis. Future studies of NMS in male mice may
      provide a useful tool as a preclinical model of male chronic urological pain
      syndromes for investigating potential pharmacological and interventional
      therapies.

PMID- 29379421
TI  - Octopamine and Tyramine Contribute Separately to the Counter-Regulatory Response
      to Sugar Deficit in Drosophila.
AB  - All animals constantly negotiate external with internal demands before and during
      action selection. Energy homeostasis is a major internal factor biasing action
      selection. For instance, in addition to physiologically regulating carbohydrate
      mobilization, starvation-induced sugar shortage also biases action selection
      toward food-seeking and food consumption behaviors (the counter-regulatory
      response). Biogenic amines are often involved when such widespread behavioral
      biases need to be orchestrated. In mammals, norepinephrine (noradrenalin) is
      involved in the counterregulatory response to starvation-induced drops in glucose
      levels. The invertebrate homolog of noradrenalin, octopamine (OA) and its
      precursor tyramine (TA) are neuromodulators operating in many different neuronal
      and physiological processes. Tyrosine-beta-hydroxylase (tbetah) mutants are
      unable to convert TA into OA. We hypothesized that tbetah mutant flies may be
      aberrant in some or all of the counter-regulatory responses to starvation and
      that techniques restoring gene function or amine signaling may elucidate
      potential mechanisms and sites of action. Corroborating our hypothesis, starved
      mutants show a reduced sugar response and their hemolymph sugar concentration is
      elevated compared to control flies. When starved, they survive longer. Temporally
      controlled rescue experiments revealed an action of the OA/TA-system during the
      sugar response, while spatially controlled rescue experiments suggest actions
      also outside of the nervous system. Additionally, the analysis of two OA- and
      four TA-receptor mutants suggests an involvement of both receptor types in the
      animals' physiological and neuronal response to starvation. These results
      complement the investigations in Apis mellifera described in our companion paper
      (Buckemuller et al., 2017).

PMID- 29379422
TI  - Spatial Frequency Selectivity Is Impaired in Dopamine D2 Receptor Knockout Mice.
AB  - Dopamine is a neurotransmitter implicated in several brain functions, including
      vision. In the present study, we investigated the impacts of the lack of D2
      dopamine receptors on the structure and function of the primary visual cortex
      (V1) of D2-KO mice using optical imaging of intrinsic signals. Retinotopic maps
      were generated in order to measure anatomo-functional parameters such as V1
      shape, cortical magnification factor, scatter, and ocular dominance. Contrast
      sensitivity and spatial frequency selectivity (SF) functions were computed from
      responses to drifting gratings. When compared to control mice, none of the
      parameters of the retinotopic maps were affected by D2 receptor loss of function.
      While the contrast sensitivity function of D2-KO mice did not differ from their
      wild-type counterparts, SF selectivity function was significantly affected as the
      optimal SF and the high cut-off frequency (p < 0.01) were higher in D2-KO than in
      WT mice. These findings show that the lack of function of D2 dopamine receptors
      had no influence on cortical structure whereas it had a significant impact on the
      spatial frequency selectivity and high cut-off. Taken together, our results
      suggest that D2 receptors play a specific role on the processing of spatial
      features in early visual cortex while they do not seem to participate in its
      development.

PMID- 29379423
TI  - Repeated Transcranial Direct Current Stimulation Induces Behavioral, Metabolic
      and Neurochemical Effects in Rats on High-Calorie Diet.
AB  - Due to its high prevalence, obesity is considered an epidemic, which stimulated
      research on non-invasive methods to reduce excess body fat. Transcranial direct
      current stimulation (tDCS) is a non-invasive technique used to modulate the
      activity of cerebral cortex, which has already found increasing interest in
      medicine as a promising methodology. The aim of this study was to analyze the
      impact of tDCS on feeding behavior, metabolic abnormalities and neurotransmitters
      in certain brain areas involved in appetite control of obese rats. The male
      Wistar rats were divided into five subgroups depending on consumed diet effect
      (lean, obese) and tDCS type (anodal, cathodal, sham, and no stimulation). Two 10
      min daily sessions of tDCS for 8 consecutive days of the study were applied. Rats
      subjected to active tDCS (anodal right or cathodal left of the prefrontal cortex)
      had reduced appetite and showed lesser body weight gain than the animals
      subjected to sham procedure or those receiving no stimulation at all.
      Furthermore, tDCS contributed to reduction of epididymal fat pads and to a
      decrease in blood concentration of leptin. Neurochemical examination revealed
      that tDCS modulated serotonin pathways of the reward-related brain areas and
      contributed to a significant decrease in the density of D2 but not D1 dopamine
      receptors in the dorsal striatum, recorded 5 h after the last stimulation. No
      significant effect of tDCS on dopamine and it's metabolites in examined brain
      regions was observed. It seems that the hypothalamus was not affected by tDCS
      application as no changes in measured neurotransmitters were detected at any
      examined time point. However, these results do not exclude the possibility of the
      delayed response of the monoamines in the examined brain areas to tDCS
      application. Altogether, these findings imply that repeated tDCS of the
      prefrontal cortex may change feeding behavior of obese rats. Either right anodal
      or left cathodal tDCS were sufficient to decrease food intake, to reduce body
      adiposity and to normalize other metabolic anomalies. These beneficial effects
      can be at least partially explained by changes in serotoninergic and in lesser
      extent dopaminergic system activity within some brain areas belonging to reward
      system.

PMID- 29379424
TI  - Unifying Speed-Accuracy Trade-Off and Cost-Benefit Trade-Off in Human Reaching
      Movements.
AB  - Two basic trade-offs interact while our brain decides how to move our body.
      First, with the cost-benefit trade-off, the brain trades between the importance
      of moving faster toward a target that is more rewarding and the increased
      muscular cost resulting from a faster movement. Second, with the speed-accuracy
      trade-off, the brain trades between how accurate the movement needs to be and the
      time it takes to achieve such accuracy. So far, these two trade-offs have been
      well studied in isolation, despite their obvious interdependence. To overcome
      this limitation, we propose a new model that is able to simultaneously account
      for both trade-offs. The model assumes that the central nervous system maximizes
      the expected utility resulting from the potential reward and the cost over the
      repetition of many movements, taking into account the probability to miss the
      target. The resulting model is able to account for both the speed-accuracy and
      the cost-benefit trade-offs. To validate the proposed hypothesis, we confront the
      properties of the computational model to data from an experimental study where
      subjects have to reach for targets by performing arm movements in a horizontal
      plane. The results qualitatively show that the proposed model successfully
      accounts for both cost-benefit and speed-accuracy trade-offs.

PMID- 29379426
TI  - Categorization for Faces and Tools-Two Classes of Objects Shaped by Different
      Experience-Differs in Processing Timing, Brain Areas Involved, and Repetition
      Effects.
AB  - The brain mechanisms that integrate the separate features of sensory input into a
      meaningful percept depend upon the prior experience of interaction with the
      object and differ between categories of objects. Recent studies using
      representational similarity analysis (RSA) have characterized either the spatial
      patterns of brain activity for different categories of objects or described how
      category structure in neuronal representations emerges in time, but never
      simultaneously. Here we applied a novel, region-based, multivariate pattern
      classification approach in combination with RSA to magnetoencephalography data to
      extract activity associated with qualitatively distinct processing stages of
      visual perception. We asked participants to name what they see whilst viewing
      bitonal visual stimuli of two categories predominantly shaped by either value
      dependent or sensorimotor experience, namely faces and tools, and meaningless
      images. We aimed to disambiguate the spatiotemporal patterns of brain activity
      between the meaningful categories and determine which differences in their
      processing were attributable to either perceptual categorization per se, or later
      stage mentalizing-related processes. We have extracted three stages of cortical
      activity corresponding to low-level processing, category-specific feature
      binding, and supra-categorical processing. All face-specific spatiotemporal
      patterns were associated with bilateral activation of ventral occipito-temporal
      areas during the feature binding stage at 140-170 ms. The tool-specific activity
      was found both within the categorization stage and in a later period not thought
      to be associated with binding processes. The tool-specific binding-related
      activity was detected within a 210-220 ms window and was located to the
      intraparietal sulcus of the left hemisphere. Brain activity common for both
      meaningful categories started at 250 ms and included widely distributed
      assemblies within parietal, temporal, and prefrontal regions. Furthermore, we
      hypothesized and tested whether activity within face and tool-specific binding
      related patterns would demonstrate oppositely acting effects following procedural
      perceptual learning. We found that activity in the ventral, face-specific network
      increased following the stimuli repetition. In contrast, tool processing in the
      dorsal network adapted by reducing its activity over the repetition period.
      Altogether, we have demonstrated that activity associated with visual processing
      of faces and tools during the categorization stage differ in processing timing,
      brain areas involved, and in their dynamics underlying stimuli learning.

PMID- 29379425
TI  - Different Topological Properties of EEG-Derived Networks Describe Working Memory
      Phases as Revealed by Graph Theoretical Analysis.
AB  - Several non-invasive imaging methods have contributed to shed light on the brain
      mechanisms underlying working memory (WM). The aim of the present study was to
      depict the topology of the relevant EEG-derived brain networks associated to
      distinct operations of WM function elicited by the Sternberg Item Recognition
      Task (SIRT) such as encoding, storage, and retrieval in healthy, middle age (46
      +/- 5 years) adults. High density EEG recordings were performed in 17
      participants whilst attending a visual SIRT. Neural correlates of WM were
      assessed by means of a combination of EEG signal processing methods (i.e., time
      varying connectivity estimation and graph theory), in order to extract synthetic
      descriptors of the complex networks underlying the encoding, storage, and
      retrieval phases of WM construct. The group analysis revealed that the encoding
      phase exhibited a significantly higher small-world topology of EEG networks with
      respect to storage and retrieval in all EEG frequency oscillations, thus
      indicating that during the encoding of items the global network organization
      could "optimally" promote the information flow between WM sub-networks. We also
      found that the magnitude of such configuration could predict subject behavioral
      performance when memory load increases as indicated by the negative correlation
      between Reaction Time and the local efficiency values estimated during the
      encoding in the alpha band in both 4 and 6 digits conditions. At the local scale,
      the values of the degree index which measures the degree of in- and out-
      information flow between scalp areas were found to specifically distinguish the
      hubs within the relevant sub-networks associated to each of the three different
      WM phases, according to the different role of the sub-network of regions in the
      different WM phases. Our findings indicate that the use of EEG-derived
      connectivity measures and their related topological indices might offer a
      reliable and yet affordable approach to monitor WM components and thus
      theoretically support the clinical assessment of cognitive functions in presence
      of WM decline/impairment, as it occurs after stroke.

PMID- 29379427
TI  - Effective Synchronization of EEG and EMG for Mobile Brain/Body Imaging in
      Clinical Settings.
AB  - Mobile Brain/Body Imaging (MoBI) is rapidly gaining traction as a new imaging
      modality to study how cognitive processes support locomotion.
      Electroencephalogram (EEG) and electromyogram (EMG), due to their time
      resolution, non-invasiveness and portability are the techniques of choice for
      MoBI, but synchronization requirements among others restrict its use to high-end
      research facilities. Here we test the effectiveness of a technique that enables
      us to achieve MoBI-grade synchronization of EEG and EMG, even when other
      strategies (such as Lab Streaming Layer (LSL)) cannot be used e.g., due to the
      unavailability of proprietary Application Programming Interfaces (APIs), which is
      often the case in clinical settings. The proposed strategy is that of aligning
      several spikes at the beginning and end of the session. We delivered a train of
      spikes to the EEG amplifier and EMG electrodes every 2 s over a 10-min time
      period. We selected a variable number of spikes (from 1 to 10) both at the
      beginning and end of the time series and linearly resampled the data so as to
      align them. We then compared the misalignment of the "middle" spikes over the
      whole recording to test for jitter and synchronization drifts, highlighting
      possible nonlinearities (due to hardware filters) and estimated the maximum
      length of the recording to achieve a [-5 to 5] ms misalignment range. We
      demonstrate that MoBI-grade synchronization can be achieved within 10-min
      recordings with a 1.7 ms jitter and [-5 5] ms misalignment range. We show that
      repeated spike delivery can be used to test online synchronization options and to
      troubleshoot synchronization issues over EEG and EMG. We also show that
      synchronization cannot rely only on the equipment sampling rate advertised by
      manufacturers. The synchronization strategy described can be used virtually in
      every clinical environment, and may increase the interest among a broader
      spectrum of clinicians and researchers in the MoBI framework, ultimately leading
      to a better understanding of the brain processes underlying locomotion control
      and the development of more effective rehabilitation approaches.

PMID- 29379429
TI  - Racial Bias in Neural Response for Pain Is Modulated by Minimal Group.
AB  - Whether empathic racial bias could be modulated is a subject of intense interest.
      The present study was carried out to explore whether empathic racial bias for
      pain is modulated by minimal group. Chinese/Western faces with neutral
      expressions receiving painful (needle penetration) or non-painful (Q-tip touch)
      stimulation were presented. Participants were asked to rate the pain intensity
      felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial
      bias were also measured. Two lines of evidence indicated that the anterior
      cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited
      stronger activity than Western did in the ACC, and (2) activity in the ACC was
      modulated by implicit racial bias. Whereas the right anterior insula (rAI) were
      modulated by ingroup bias, in which ingroup member elicited stronger activity
      than outgroup member did. Furthermore, activity in the ACC was modulated by
      activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the
      rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition.
      Our results provide evidence that there are different neural correlates for
      racial bias and ingroup bias, and neural racial bias for pain can be modulated by
      minimal group.

PMID- 29379431
TI  - Benchmark Dataset for Evaluation of Range-Based People Tracker Classifiers in
      Mobile Robots.

PMID- 29379428
TI  - Sexual Abuse Exposure Alters Early Processing of Emotional Words: Evidence from
      Event-Related Potentials.
AB  - This study aimed to compare the time course of emotional information processing
      between trauma-exposed and control participants, using electrophysiological
      measures. We conceived an emotional Stroop task with two types of words: trauma
      related emotional words and neutral words. We assessed the evoked cerebral
      responses of sexual abuse victims without post-traumatic stress disorder (PTSD)
      and no abuse participants. We focused particularly on an early wave (C1/P1), the
      N2pc, and the P3b. Our main result indicated an early effect (55-165 ms) of
      emotionality, which varied between non-exposed participants and sexual abuse
      victims. This suggests that potentially traumatic experiences modulate early
      processing of emotional information. Our findings showing neurobiological
      alterations in sexual abuse victims (without PTSD) suggest that exposure to
      highly emotional events has an important impact on neurocognitive function even
      in the absence of psychopathology.

PMID- 29379430
TI  - Perfect Detection of Spikes in the Linear Sub-threshold Dynamics of Point
      Neurons.
AB  - Spiking neuronal networks are usually simulated with one of three main schemes:
      the classical time-driven and event-driven schemes, and the more recent hybrid
      scheme. All three schemes evolve the state of a neuron through a series of
      checkpoints: equally spaced in the first scheme and determined neuron-wise by
      spike events in the latter two. The time-driven and the hybrid scheme determine
      whether the membrane potential of a neuron crosses a threshold at the end of the
      time interval between consecutive checkpoints. Threshold crossing can, however,
      occur within the interval even if this test is negative. Spikes can therefore be
      missed. The present work offers an alternative geometric point of view on
      neuronal dynamics, and derives, implements, and benchmarks a method for perfect
      retrospective spike detection. This method can be applied to neuron models with
      affine or linear subthreshold dynamics. The idea behind the method is to
      propagate the threshold with a time-inverted dynamics, testing whether the
      threshold crosses the neuron state to be evolved, rather than vice versa.
      Algebraically this translates into a set of inequalities necessary and sufficient
      for threshold crossing. This test is slower than the imperfect one, but can be
      optimized in several ways. Comparison confirms earlier results that the imperfect
      tests rarely miss spikes (less than a fraction 1/108 of missed spikes) in
      biologically relevant settings.

PMID- 29379432
TI  - Smartphone Applications Can Serve as Effective Cognitive Training Tools in
      Healthy Aging.

PMID- 29379433
TI  - Ventricular and Periventricular Anomalies in the Aging and Cognitively Impaired
      Brain.
AB  - Ventriculomegaly (expansion of the brain's fluid-filled ventricles), a condition
      commonly found in the aging brain, results in areas of gliosis where the
      ependymal cells are replaced with dense astrocytic patches. Loss of ependymal
      cells would compromise trans-ependymal bulk flow mechanisms required for
      clearance of proteins and metabolites from the brain parenchyma. However, little
      is known about the interplay between age-related ventricle expansion, the decline
      in ependymal integrity, altered periventricular fluid homeostasis, abnormal
      protein accumulation and cognitive impairment. In collaboration with the
      Baltimore Longitudinal Study of Aging (BLSA) and Alzheimer's Disease Neuroimaging
      Initiative (ADNI), we analyzed longitudinal structural magnetic resonance imaging
      (MRI) and subject-matched fluid-attenuated inversion recovery (FLAIR) MRI and
      periventricular biospecimens to map spatiotemporally the progression of ventricle
      expansion and associated periventricular edema and loss of transependymal
      exchange functions in healthy aging individuals and those with varying degrees of
      cognitive impairment. We found that the trajectory of ventricle expansion and
      periventricular edema progression correlated with degree of cognitive impairment
      in both speed and severity, and confirmed that areas of expansion showed
      ventricle surface gliosis accompanied by edema and periventricular accumulation
      of protein aggregates, suggesting impaired clearance mechanisms in these regions.
      These findings reveal pathophysiological outcomes associated with normal brain
      aging and cognitive impairment, and indicate that a multifactorial analysis is
      best suited to predict and monitor cognitive decline.

PMID- 29379434
TI  - Dual Action of Mexiletine and Its Pyrroline Derivatives as Skeletal Muscle Sodium
      Channel Blockers and Anti-oxidant Compounds: Toward Novel Therapeutic Potential.
AB  - Mexiletine (Mex) has been recently appointed as an orphan-drug in myotonic
      syndromes, being a potent use-dependent blocker of skeletal-muscle sodium
      channels (NaV1.4). Available evidences about a potential anti-oxidant effect of
      Mex and its tetramethyl-pyrroline-derivatives in vivo, suggest the possibility to
      further enlarge the therapeutic potential of Mex-like compounds in myopathies in
      which alteration of excitation-contraction coupling is paralleled by oxidative
      stress. In line with this and based on our previous structure-activity
      relationship studies, we synthesized new compounds with a tetramethyl-pyrroline
      ring on the amino-group of both Mex (VM11) and of its potent use-dependent
      isopropyl-derivative (CI16). The compounds were tested for their ability to block
      native NaV1.4 and to exert cyto-protective effects against oxidative-stress
      injury in myoblasts. Voltage-clamp-recordings on adult myofibers were performed
      to assess the tonic and use-dependent block of peak sodium-currents (INa) by VM11
      and CI16, as well as Mex, VM11 and CI16 were 3 and 6-fold more potent than Mex in
      producing a tonic-block of peak sodium-currents (INa), respectively.
      Interestingly, CI16 showed a 40-fold increase of potency with respect to Mex
      during high-frequency stimulation (10-Hz), resulting the strongest use-dependent
      Mex-like compound so far. The derivatives also behaved as inactivated channel
      blockers, however the voltage dependent block was modest. The experimental data
      fitted with the molecular-modeling simulation based on previously proposed
      interaction of main pharmacophores with NaV1.4 binding-site. CI16 and VM11 were
      then compared to Mex and its isopropyl derivative (Me5) for the ability to
      protect C2C12-cells from H2O2-cytotoxicity in the concentration range effective
      on Nav1.4. Mex and Me5 showed a moderate cyto-protective effect in the presence
      of H2O2, Importantly, CI16 and VM11 showed a remarkable cyto-protection at
      concentrations effective for use-dependent block of NaV1.4. This effect was
      comparable to that of selected anti-oxidant drugs proved to exert protective
      effect in preclinical models of progressive myopathies such as muscular
      dystrophies. Then, the tetramethyl-pyrroline compounds have increased therapeutic
      profile as sodium channel blockers and an interesting cyto-protective activity.
      The overall profile enlarges therapeutic potential from channelopathies to
      myopathies in which alteration of excitation-contraction coupling is paralleled
      by oxidative-stress, i.e., muscular dystrophies.

PMID- 29379435
TI  - Antioxidants Attenuate Isolation- and L-DOPA-Induced Aggression in Mice.
AB  - Aggression is a major hallmark worldwide attributing negative traits in
      personality. Wide variety of antioxidants is used for the treatment of many
      ailments. The present study was conducted to evaluate the role of antioxidants
      such as ascorbic acid (15.42 and 30.84 mg/kg), beta carotene (1.02 and 2.05
      mg/kg), vitamin E (2.5 and 5.0 mg/kg), and N-acetyl cysteine (102.85 and 205.70
      mg/kg) in the treatment of aggression. Two aggression models (isolation induced
      aggression model and L-DOPA induced aggression model) were used in the study.
      Male albino mice (n = 330) were used in the study which were further subdivided
      into 11 groups (Group I-control, group II-diseased, group III-standard group,
      group IV-V treated with ascorbic, group VI-VII treated with beta carotene, group
      VIII-IX treated with vitamin E, group X-XI treated with N-acetyl cysteine for 14
      consecutive days). Different biochemical markers (glutathione, superoxide
      dismutase, and catalase) were determined to evaluate the antioxidant potential in
      oxidative stress. High dose of vitamin E (5.0 mg/kg) was more effective to reduce
      the aggression in isolated animals while all other antioxidants produced dose
      dependent anti-aggressive effect except N-acetyl cysteine which had marked anti
      aggressive effect at low dose (102.75 mg/kg). Low doses of vitamin E (2.5 mg/kg)
      and N-acetyl cysteine (102.75 mg/kg) and high dose of beta carotene (2.05 mg/kg)
      were effective to prevent all aggression parameters in acute anti-aggressive
      activity against L-DOPA induced aggression. However, all test antioxidants were
      equally effective in chronic anti-aggressive studies against L-DOPA induced
      aggression. It may be concluded that selected antioxidants can reverse the
      aggression which is a key symptom of many neurological disorder.

PMID- 29379436
TI  - Dendrobium officinale Orchid Extract Prevents Ovariectomy-Induced Osteoporosis in
      Vivo and Inhibits RANKL-Induced Osteoclast Differentiation in Vitro.
AB  - Background:Dendrobium officinale, a traditional Chinese medical herb with high
      value that is widely used in Asia, possesses many positive effects on human
      health, including anti-chronic inflammation, anti-obesity, and immune modulation
      properties; however, whether D. officinale has inhibitory effects on
      postmenopausal osteoporosis remains unknown. Objective: We investigated the
      effects of D. officinale extract (DOE) on ovariectomy-induced bone loss in vivo
      and on osteoclastogenesis in vitro. Methods:In vivo, female rats were divided
      into a sham-operated (sham) group and five ovariectomized (OVX) subgroups: OVX
      with vehicle (OVX), OVX with Xian-Ling-Gu-Bao capsule (240 mg/kg body
      weight/day), and OVX with low-, medium-, and high-dose DOE (150, 300, and 600
      mg/kg body weight/day, respectively). Animals in each group were administered
      their corresponding treatments for 13 weeks. Body weight, serum biochemical
      parameters, uterine and femoral physical parameters, bone mineral density (BMD),
      bone biomechanical properties, and bone microarchitecture were obtained. In
      vitro, the effects of DOE on osteoclastogenesis were examined using RAW264.7
      cells. The effects of DOE on osteoclastogenesis and the expression of osteoclast
      specific marker genes and proteins were determined. Results: DOE effectively
      ameliorated serum biochemical parameters, especially alleviated estradiol (E2)
      deficiency and maintained calcium and phosphorus homeostasis. DOE improved
      uterine and femoral physical parameters. In addition, DOE improved femoral BMD
      and biomechanical properties. DOE significantly ameliorated bone
      microarchitecture. Moreover, DOE inhibited osteoclastogenesis independent of its
      cytoxicity and suppressed the expression of osteoclast-specific marker genes and
      proteins. Conclusion: DOE can effectively prevent ovariectomy-induced bone loss
      in vivo and inhibit osteoclastogenesis in vitro.

PMID- 29379437
TI  - Socioeconomic Inequalities in Overweight and Obesity in Serbia: Data from 2013
      National Health Survey.

PMID- 29379438
TI  - Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer.
AB  - Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains at the forefront of
      immunotherapy for treating bladder cancer patients. However, the incidence of
      recurrence and progression to invasive cancer is commonly observed. There are no
      established effective intravesical therapies available for patients, whose tumors
      recur following BCG treatment, representing an important unmet clinical need. In
      addition, there are very limited options for patients who do not respond to or
      tolerate chemotherapy due to toxicities, resulting in poor overall treatment
      outcomes. Within this context, nanotechnology is an emergent and promising tool
      for: (1) controlling drug release for extended time frames, (2) combination
      therapies due to the ability to encapsulate multiple drugs simultaneously, (3)
      reducing systemic side effects, (4) increasing bioavailability, (5) and
      increasing the viability of various routes of administration. Moreover, bladder
      cancer is often characterized by high mutation rates and over expression of tumor
      antigens on the tumor cell surface. Therapeutic targeting of these biomolecules
      may be improved by nanotechnology strategies. In this mini-review, we discuss how
      nanotechnology can help overcome current obstacles in bladder cancer treatment,
      and how nanotechnology can facilitate combination chemotherapeutic and BCG
      immunotherapies for the treatment of non-muscle invasive urothelial bladder
      cancer.

PMID- 29379439
TI  - S-Ketamine Mediates Its Acute and Sustained Antidepressant-Like Activity through
      a 5-HT1B Receptor Dependent Mechanism in a Genetic Rat Model of Depression.
AB  - Rationale: The mechanisms responsible for the unique antidepressant properties of
      ketamine have only been partly resolved. Recent preclinical reports implicate the
      neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] in the antidepressant
      like response of ketamine, and modulation of 5-HT1B receptors has been
      hypothesized to attain an important role. Objectives: To evaluate the role of
      endogenous stimulation of 5-HT1B heteroreceptors in the antidepressant-like
      activity of S-ketamine. Method: Flinders sensitive line (FSL) rats, a genetic
      model of depression, were depleted of endogenous 5-HT by 4-chloro-DL
      phenylalanine methyl ester HCl administration (pCPA; 86 mg/kg/day for 3 days). In
      pCPA-pretreated and control FSL rats, the acute and sustained effects of a single
      dose of S-ketamine (15 mg/kg) and the selective 5-HT1B receptor agonist CP94253
      (1-6 mg/kg) alone and in combination with S-ketamine were studied in the forced
      swim test (FST), a commonly used assay that detects antidepressant activity.
      Results: pCPA pretreatment decreased cortical 5-HT levels to ~6% but did not
      affect the baseline behavioral phenotype of FSL rats. S-ketamine demonstrated
      acute and sustained antidepressant-like activity, both of which were abolished by
      5-HT depletion. Combining S-ketamine with a sub-effective dose of CP94253 (1
      mg/kg) rescued S-ketamine's acute and sustained antidepressant-like effects, when
      CP94253 was administered 2 h prior to the FST. Co-administration of S-ketamine
      and CP94253 did not affect the plasma level of either compound, suggesting that
      the observed behavioral interaction could not be ascribed to a kinetic drug-drug
      interaction. Conclusion: 5-HT1B receptor activation during testing appears to be
      critical for S-ketamine's antidepressant-like potentials in this model.

PMID- 29379440
TI  - Gleditsia Saponin C Induces A549 Cell Apoptosis via Caspase-Dependent Cascade and
      Suppresses Tumor Growth on Xenografts Tumor Animal Model.
AB  - Saponins are natural compounds and possess the most promising anti-cancer
      function. Here, a saponin gleditsia saponin C (GSC), extracted from gleditsiae
      fructus abnormalis, could induce apoptosis of lung tumor cell line A549 via
      caspase dependent cascade and this effect could be prevented by the caspase
      inhibitors. In addition, GSC induced cell death companied with an increase ratio
      of Bax:Bcl-2 and inhibition of ERK and Akt signaling pathways. Meanwhile, GSC
      suppressed TNFalpha inducing NF-kappaB activation and increased the
      susceptibility of lung cancer cell to TNFalpha induced apoptosis. Furthermore, on
      mouse xenograft model, GSC significantly suppressed tumor growth and induced
      cancer cell apoptosis, which validated the anti-tumor effect of GSC. Based on
      these results, GSC might be a promising drug candidate of anti-lung cancer for
      its potential clinical applications.

PMID- 29379441
TI  - Deciphering the Differential Effective and Toxic Responses of Bupleuri Radix
      following the Induction of Chronic Unpredictable Mild Stress and in Healthy Rats
      Based on Serum Metabolic Profiles.
AB  - The petroleum ether fraction of Bupleuri Radix which is contained in the
      traditional Chinese medicine prescription of Xiaoyaosan (XYS) may have a
      therapeutic effect in depressed subjects based on the results of our previous
      study. It has been reported that Bupleuri Radix can cause liver toxicity
      following overdosing or long-term use. Therefore, this study aimed to decipher
      the differential effective and toxic responses of Bupleuri Radix in chronic
      unpredictable mild stress (CUMS) (with depression) and healthy rats based on
      serum metabolic profiles. Serum metabolic profiles were obtained using the UHPLC-
      Q Exactive Orbitrap-MS technique. Our results demonstrated that the petroleum
      ether fraction of Bupleuri Radix (PBR) produces an antidepressant effect through
      regulating glycometabolism, amino acid metabolism, sphingolipid metabolism,
      glycerophospholipid metabolism, and fatty acid metabolism. It also induces more
      severe toxic reactions in the liver or kidney in healthy rats than in CUMS rats,
      which exhibited a comparatively mild drug-induced toxic reaction. The altered
      lysine degradation, sphingolipid metabolism, glycerophospholipid metabolism,
      fatty acid metabolism, and bile acid metabolism could be at least partly
      responsible for the PBR toxic responses in healthy rats. The differential
      effective and toxic response of PBR in CUMS rats and healthy rats provide a new
      standard for the more rational and safer application of clinical drugs in the
      future.

PMID- 29379442
TI  - Hypouricemic Effects of Ganoderma applanatum in Hyperuricemia Mice through OAT1
      and GLUT9.
AB  - Ganoderma applanatum (G. applanatum) dispels wind to eliminate dampness and
      exhibited nephron- and liver-protective effects as noted in Chinese herbal
      classic literature; it might also affect hyperuricemia. Therefore, we examined
      the hypouricemia effects and mechanisms underlying G. applanatum on chemical
      induced hyperuricemia in mice. Ethanol (GAE) and water (GAW) extracts were
      prepared by extracting G. applanatum in ethanol (GAE), followed by bathing the
      remains in water to yield GAW. GAE and GAW were administered orally at different
      doses to hyperuricemia mice, while allopurinol and benzbromarone served as
      positive controls. Both GAE and GAW showed remarkable hypouricemia activities,
      rendering a substantial decline in the SUA (serum uric acid) level in
      hyperuricemia control (P < 0.01). Moreover, the urine uric acid (UUA) levels were
      enhanced by GAE and GAW. In contrast to the evident renal toxicity of
      allopurinol, GAE and GAW did not show a distinct renal toxicity. Almost no
      suppressing effect was observed on the XOD activities. However, compared to the
      hyperuricemia control, OAT1 was elevated remarkably in mice drugged with GAE and
      GAW, while GLUT9 was significantly decreased. Similar to benzbromarone, GAE
      decreased the URAT1 protein levels significantly (P < 0.01), while GAW did not
      display a similar effect. GAE and GAW downregulated the level of CNT2 proteins in
      the gastrointestinal tract of hyperuricemia mice. Thus, G. applanatum produced
      outstanding hypouricemic effects, mediated by renal OAT1, GLUT9, and URAT1 and
      gastrointestinal CNT2 that might elevate urine uric secretions and decline in the
      absorption of purine in the gastrointestinal tracts. G. applanatum showed little
      negative influence on inner organs. By docking screening, four top-ranked
      compounds were identified that necessitated further investigation. Compounds:
      potassium oxonate, hypoxanthine, allopurinol, benzbromarone.

PMID- 29379443
TI  - A Status Review of the Bioactive Activities of Tiger Milk Mushroom Lignosus
      rhinocerotis (Cooke) Ryvarden.
AB  - Edible and medicinal mushrooms are regularly used in natural medicines and home
      remedies since antiquity for ailments like fever, inflammation, and respiratory
      disorders. Lignosus rhinocerotis (Cooke) Ryvarden is a polypore found in Malaysia
      and other regions in South East Asia. It can be located on a spot where a tigress
      drips milk while feeding, hence the name "tiger's milk mushroom." The sclerotium
      of L. rhinocerotis is highly sought after by the native communities in Malaysia
      to stave off hunger, relieve cough and asthma, and provide stamina. The genomic
      features of L. rhinocerotis have been described. The pharmacological and toxicity
      effects, if any, of L. rhinocerotis sclerotium have been scientifically verified
      in recent years. In this review, the validated investigations including the
      cognitive function, neuroprotection, immune modulation, anti-asthmatic, anti
      coagulation, anti-inflammatory, anti-microbial/ anti-viral, anti-obesity, anti
      cancer/ anti-tumor, and antioxidant properties are highlighted. These findings
      suggest that L. rhinocerotis can be considered as an alternative and natural
      medicine in the management of non-communicable diseases. However, there is a
      paucity of validation studies including human clinical trials of the
      mycochemicals of L. rhinocerotis.

PMID- 29379444
TI  - A Doubly Stochastic Change Point Detection Algorithm for Noisy Biological
      Signals.
AB  - Experimentally and clinically collected time series data are often contaminated
      with significant confounding noise, creating short, noisy time series. This
      noise, due to natural variability and measurement error, poses a challenge to
      conventional change point detection methods. We propose a novel and robust
      statistical method for change point detection for noisy biological time
      sequences. Our method is a significant improvement over traditional change point
      detection methods, which only examine a potential anomaly at a single time point.
      In contrast, our method considers all suspected anomaly points and considers the
      joint probability distribution of the number of change points and the elapsed
      time between two consecutive anomalies. We validate our method with three
      simulated time series, a widely accepted benchmark data set, two geological time
      series, a data set of ECG recordings, and a physiological data set of heart rate
      variability measurements of fetal sheep model of human labor, comparing it to
      three existing methods. Our method demonstrates significantly improved
      performance over the existing point-wise detection methods.

PMID- 29379446
TI  - Assessment of Fetal Kidney Growth and Birth Weight in an Indigenous Australian
      Cohort.
AB  - Introduction: Indigenous Australians experience higher rates of renal disease and
      hypertension than non-Indigenous Australians. Low birth weight is recognized as a
      contributing factor in chronic disease and has been shown to increase the risk of
      renal failure in adulthood. A smaller kidney volume with fewer nephrons places an
      individual at risk of hypertension and renal failure. Indigenous Australians have
      fewer nephrons than non-Indigenous Australians. In this study, intrauterine fetal
      and kidney growth were evaluated in 174 Indigenous Australian babies throughout
      gestation in order to record and evaluate fetal growth and kidney size, within a
      population that is at high risk for chronic illness. Methods: Pregnant women that
      identified as Indigenous, or non-Indigenous women that were pregnant with a
      partner who identified as an Indigenous Australian were eligible to participate.
      Maternal history, smoking status, blood and urine samples and fetal ultrasounds
      were collected throughout pregnancy. Fetal kidney measurements were collected
      using ultrasound. Statistical analysis was performed using the Stata 14.1
      software package. Results: 15.2% of babies were born prematurely. 44% of the
      mothers reported smoking in pregnancy. The median birth weight of this cohort was
      3,240 g. Male fetuses had higher kidney to body weight ratios than female fetuses
      (P = 0.02). The birth weights of term neonates whose mothers smoked during
      pregnancy were lower (327 g, P < 0.001) than the birth weights of term babies
      from non-smoking mothers. The kidney volumes of babies whose mothers smoked were
      also smaller (P = 0.02), but were in proportion to body weight. Conclusion: In
      this cohort of Indigenous women smoking was associated with both increased number
      of preterm births and with a reduction in birth weights, even of term infants.
      Since kidney volume is a surrogate measure of nephron number and nephrogenesis is
      complete at birth, babies whose mothers smoked during pregnancy must have fewer
      nephrons than those from non-smoking mothers. Previous studies have shown that
      glomerular filtration rate is not related to birth weight, thus infants with
      smaller kidney volumes are hyperfiltering from birth and therefore are likely to
      be more susceptible to early onset renal disease in later life.

PMID- 29379445
TI  - Physiologic Impact of Circulating RBC Microparticles upon Blood-Vascular
      Interactions.
AB  - Here, we review current data elucidating the role of red blood cell derived
      microparticles (RMPs) in normal vascular physiology and disease progression.
      Microparticles (MPs) are submicron-size, membrane-encapsulated vesicles derived
      from various parent cell types. MPs are produced in response to numerous stimuli
      that promote a sequence of cytoskeletal and membrane phospholipid changes and
      resulting MP genesis. MPs were originally considered as potential biomarkers for
      multiple disease processes and more recently are recognized to have pleiotropic
      biological effects, most notably in: promotion of coagulation, production and
      handling of reactive oxygen species, immune modulation, angiogenesis, and in
      initiating apoptosis. RMPs, specifically, form normally during RBC maturation in
      response to injury during circulation, and are copiously produced during
      processing and storage for transfusion. Notably, several factors during RBC
      storage are known to trigger RMP production, including: increased intracellular
      calcium, increased potassium leakage, and energy failure with ATP depletion. Of
      note, RMP composition differs markedly from that of intact RBCs and the
      nature/composition of RMP components are affected by the specific circumstances
      of RMP genesis. Described RMP bioactivities include: promotion of coagulation,
      immune modulation, and promotion of endothelial adhesion as well as influence
      upon vasoregulation via influence upon nitric oxide (NO) bioavailability. Of
      particular relevance, RMPs scavenge NO more avidly than do intact RBCs; this
      physiology has been proposed to contribute to the impaired oxygen delivery
      homeostasis that may be observed following transfusion. In summary, RMPs are
      submicron particles released from RBCs, with demonstrated vasoactive properties
      that appear to disturb oxygen delivery homeostasis. The clinical impact of RMPs
      in normal and patho-physiology and in transfusion recipients is an area of
      continued investigation.

PMID- 29379447
TI  - Increased Contractile Function of Human Saphenous Vein Grafts Harvested by "No
      Touch" Technique.
AB  - Saphenous vein grafts are the most common conduits used for coronary artery
      bypass grafting (CABG); however, no more than 60% of vein grafts remain open
      after 10 years and graft failure is associated with poor clinical outcome. The
      "no-touch" harvesting technique-where a sheet of perivascular tissue is retained
      around the vein-improves graft patency to over 80% after 16 years of follow-up,
      but the mechanism for the improved patency rate is unclear. In this study, we
      investigated acute functional differences between vein grafts harvested
      conventionally and by "no-touch" technique and explored the importance of
      perivascular tissue for reducing surgical trauma, minimizing excessive
      distension, and releasing vasoactive paracrine factors. Segments of human
      saphenous veins were obtained from CABG surgery and their functional properties
      investigated by isometric and isobaric myography. We found a broad diameter
      tension relationship for human saphenous veins, with peak capacity for active
      tension development at diameters corresponding to transmural pressures around 60
      mmHg. Across the investigated transmural pressure range between 10 and 120 mmHg,
      maximal tension development was higher for "no-touch" compared to conventionally
      harvested saphenous veins. Contractile responses to serotonin, noradrenaline, and
      depolarization induced with elevated extracellular [K+] were significantly larger
      for saphenous veins harvested by "no-touch" compared to conventional technique.
      Conventional vein grafts are routinely pressurized manually in order to test for
      leaks; however, avoiding this distension procedure did not change the acute
      contractile function of the conventionally excised saphenous veins. In contrast,
      even though surgical removal of perivascular tissue during conventional
      harvesting was associated with a substantial decrease in force development,
      removal of perivascular tissue by careful dissection under a stereomicroscope
      only marginally affected contractile responses of veins harvested by "no-touch"
      technique. In conclusion, we show that saphenous veins harvested by "no-touch"
      technique have greater contractile capacity than veins harvested by conventional
      technique. The different capacity for smooth muscle contraction is not due to
      vasoactive substances released by the perivascular tissue. Instead, we propose
      that the larger tension development of saphenous veins harvested by "no-touch"
      technique reflects reduced surgical damage, which may have long-term consequences
      that contribute to the superior graft patency.

PMID- 29379449
TI  - Increased Loss Aversion in Unmedicated Patients with Obsessive-Compulsive
      Disorder.
AB  - Introduction: Obsessive-compulsive disorder (OCD) patients show abnormalities in
      decision-making and, clinically, appear to show heightened sensitivity to
      potential negative outcomes. Despite the importance of these cognitive processes
      in OCD, few studies have examined the disorder within an economic decision-making
      framework. Here, we investigated loss aversion, a key construct in the prospect
      theory that describes the tendency for individuals to be more sensitive to
      potential losses than gains when making decisions. Methods: Across two study
      sites, groups of unmedicated OCD patients (n = 14), medicated OCD patients (n =
      29), and healthy controls (n = 34) accepted or rejected a series of 50/50 gambles
      containing varying loss/gain values. Loss aversion was calculated as the ratio of
      the likelihood of rejecting a gamble with increasing potential losses to the
      likelihood of accepting a gamble with increasing potential gains. Decision times
      to accept or reject were also examined and correlated with loss aversion.
      Results: Unmedicated OCD patients exhibited significantly more loss aversion
      compared to medicated OCD or controls, an effect that was replicated across both
      sites and remained significant even after controlling for OCD symptom severity,
      trait anxiety, and sex. Post hoc analyses further indicated that unmedicated
      patients' increased likelihood to reject a gamble as its loss value increased
      could not be explained solely by greater risk aversion among patients.
      Unmedicated patients were also slower to accept than reject gambles, effects that
      were not found in the other two groups. Loss aversion was correlated with
      decision times in unmedicated patients but not in the other two groups.
      Discussion: These data identify abnormalities of decision-making in a subgroup of
      OCD patients not taking psychotropic medication. The findings help elucidate the
      cognitive mechanisms of the disorder and suggest that future treatments could aim
      to target abnormalities of loss/gain processing during decision-making in this
      population.

PMID- 29379450
TI  - A Diffusion Model Analysis of Magnitude Comparison in Children with and without
      Dyscalculia: Care of Response and Ability Are Related to Both Mathematical
      Achievement and Stimuli.
AB  - The respective roles of the approximate number system (ANS) and an access deficit
      (AD) in developmental dyscalculia (DD) are not well-known. Most studies rely on
      response times (RTs) or accuracy (error rates) separately. We analyzed the
      results of two samples of elementary school children in symbolic magnitude
      comparison (MC) and non-symbolic MC using a diffusion model. This approach uses
      the joint distribution of both RTs and accuracy in order to synthesize measures
      closer to ability and response caution or response conservatism. The latter can
      be understood in the context of the speed-accuracy tradeoff: It expresses how
      much a subject trades in speed for improved accuracy. We found significant
      effects of DD on both ability (negative) and response caution (positive) in MC
      tasks and a negative interaction of DD with symbolic task material on ability.
      These results support that DD subjects suffer from both an impaired ANS and an AD
      and in particular support that slower RTs of children with DD are indeed related
      to impaired processing of numerical information. An interaction effect of
      symbolic task material and DD (low mathematical ability) on response caution
      could not be refuted. However, in a sample more representative of the general
      population we found a negative association of mathematical ability and response
      caution in symbolic but not in non-symbolic task material. The observed
      differences in response behavior highlight the importance of accounting for
      response caution in the analysis of MC tasks. The results as a whole present a
      good example of the benefits of a diffusion model analysis.

PMID- 29379448
TI  - Progress in Mathematical Modeling of Gastrointestinal Slow Wave Abnormalities.
AB  - Gastrointestinal (GI) motility is regulated in part by electrophysiological
      events called slow waves, which are generated by the interstitial cells of Cajal
      (ICC). Slow waves propagate by a process of "entrainment," which occurs over a
      decreasing gradient of intrinsic frequencies in the antegrade direction across
      much of the GI tract. Abnormal initiation and conduction of slow waves have been
      demonstrated in, and linked to, a number of GI motility disorders. A range of
      mathematical models have been developed to study abnormal slow waves and applied
      to propose novel methods for non-invasive detection and therapy. This review
      provides a general outline of GI slow wave abnormalities and their recent
      classification using multi-electrode (high-resolution) mapping methods, with a
      particular emphasis on the spatial patterns of these abnormal activities. The
      recently-developed mathematical models are introduced in order of their
      biophysical scale from cellular to whole-organ levels. The modeling techniques,
      main findings from the simulations, and potential future directions arising from
      notable studies are discussed.

PMID- 29379451
TI  - Ecological Assets and Academic Procrastination among Adolescents: The Mediating
      Role of Commitment to Learning.
AB  - Academic procrastination is defined as a purposive delay of academic tasks that
      must be completed. Within the framework of the ecological model of resiliency,
      this study examined how ecological assets were related to academic
      procrastination among adolescents. Participants in the study were 577 adolescents
      (53.5% boys) from Shanghai, China. They completed measures of ecological assets,
      commitment to learning, and academic procrastination. Structural equation
      modeling revealed that, as predicted, ecological assets were negatively
      associated with academic procrastination. In addition, commitment to learning
      fully mediated the association between ecological assets and academic
      procrastination. Implications of the present findings are discussed.

PMID- 29379453
TI  - Length of Utterance, in Morphemes or in Words?: MLU3-w, a Reliable Measure of
      Language Development in Early Basque.
AB  - The mean length of utterace (MLU), which was proposed by Brown (1973) as a better
      index for language development in children than age, has been regularly reported
      in case studies as well as in cross-sectional studies on early spontaneous
      language production. Despite the reliability of MLU as a measure of (morpho
      )syntactic development having been called into question, its extensive use in
      language acquisition studies highlights its utility not only for intra- and inter
      individual comparison in monolingual language acquisition, but also for cross
      linguistic assessment and comparison of bilinguals' early language development
      (Muller, 1993; Yip and Matthews, 2006; Meisel, 2011). An additional issue
      concerns whether MLU should be measured in words (MLU-w) or morphemes (MLU-m),
      the latter option being the most difficult to gauge, since new challenges have
      arisen regarding how to count zero morphemes, suppletive and fused morphemes. The
      different criteria have consequences, especially when comparing development in
      languages with diverging morphological complexity. A variant of MLU, the MLU3,
      which is calculated out of the three longest sentences produced (MLU3-w and MLU3
      m), is included among the subscales of expressive language development in CDI
      parental reports (Fenson et al., 1993, 2007). The aim of the study is to
      investigate the consistency and utility of MLU3-w and MLU3-m as a measure for
      (morpho-)syntactic development in Basque, an agglutinative language. To that end,
      cross-sectional data were obtained using either the Basque CDI-2 instrument (16-
      to 30-month-olds) or the Basque CDI-3 (30- to 50-month-olds). The results of
      analyzing reports on over 1,200 children show three main findings. First, MLU3-w
      and MLU3-m can report equally well on very young children's development. Second,
      the strong correlations found between MLU3 and expressive vocabulary in the
      Basque CDI-2 and CDI-3 instruments, as well as between MLU3 and both nominal and
      verbal morphology scales, confirm the consistency not only of MLU3 but also of
      the two Basque CDI instruments. Finally, both MLU3-w and MLU3-m subscales appear
      sensitive to input after age 2, which emphasizes their utility for identifying
      developmental patterns in Basque bilinguals.

PMID- 29379452
TI  - Investigation of Psychophysiological and Subjective Effects of Long Working Hours
      - Do Age and Hearing Impairment Matter?
AB  - Following current prognosis, demographic development raises expectations of an
      aging of the working population. Therefore, keeping employees healthy and
      strengthening their ability to work, becomes more and more important. When
      employees become older, dealing with age-related impairments of sensory
      functions, such as hearing impairment, is a central issue. Recent evidence
      suggests that negative effects that are associated with reduced hearing can have
      a strong impact at work. Especially under exhausting working situations such as
      working overtime hours, age and hearing impairment might influence employees'
      well-being. Until now, neither the problem of aged workers and long working
      hours, nor the problem of hearing impairment and prolonged working time has been
      addressed explicitly. Therefore, a laboratory study was examined to answer the
      research question: Do age and hearing impairment have an impact on
      psychophysiological and subjective effects of long working hours. In total, 51
      white-collar workers, aged between 24 and 63 years, participated in the
      laboratory study. The results show no significant effects for age and hearing
      impairment on the intensity of subjective consequences (perceived recovery and
      fatigue, subjective emotional well-being and physical symptoms) of long working
      hours. However, the psychophysiological response (the saliva cortisol level) to
      long working hours differs significantly between hearing impaired and normal
      hearing employees. Interestingly, the results suggest that from a
      psychophysiological point of view long working hours were more demanding for
      normal hearing employees.

PMID- 29379454
TI  - Motivation and Justice at Work: The Role of Emotion and Cognition Components of
      Personal and Collective Work Identity.
AB  - The aim of this study was to investigate the role of personal and collective work
      identity (including emotion and cognition components), in predicting work
      motivation (operationalized as work self-determined motivation) and
      organizational justice (operationalized as organizational pay justice). Digitized
      questionnaires were distributed by e-mail to 2905 members, teachers, of a Swedish
      trade union. A total of 768 individuals answered the questionnaire and by that
      participated in this study. Personal- compared to collective work identity was
      shown to positively associate with self-determined motivation accounted for by
      the emotion component of personal work identity. Collective compared to personal
      work identity was reported to positively associate with organizational pay
      justice accounted for by the cognition component of collective work identity. All
      this suggests that both work-related motivation and organizational justice might
      be, to some extent, accounted for by the psychological mechanisms of work
      identity and that, as predicted, different types of work identity, play different
      significant roles in predicting motivation and justice at work. More precisely,
      the emotion component of work identity was more pronounced in personal work
      bonding relationships, and the cognitive component, of work identity in contrast,
      was more pronounced in collective work-bonding relationships.

PMID- 29379456
TI  - Cultivating Positive Youth Development, Critical Consciousness, and Authentic
      Care in Urban Environmental Education.
AB  - This paper addresses the issue of how to provide affordances for youth
      development in the context of environmental stewardship in cities. Urban
      environmental education encompasses place-based and action-oriented stewardship
      practices, including community gardening and vegetable production, often with the
      dual goals of developing youth and community assets. Yet in-depth understanding
      of how these goals are achieved is lacking. Using narrative inquiry, we explored
      participant experiences in a multi-year agriculture internship program conducted
      by the food justice organization East New York Farms! (ENYF) in Brooklyn, NY.
      Emerging from our conversations with youth were five themes defining their intern
      experience: ENYF as somewhere to belong, to be pushed, to grapple with
      complexity, to practice leadership, and to become yourself. We propose a theory
      of change that emphasizes politicized notions of caring as a foundation for
      cultivating developmental assets, including competence, contribution, and
      critical consciousness, among youth who participate in ENYF programs multiple
      years. This paper extends the literature on socio-environmental affordances to
      encompass urban environmental education programs, which incorporate physical and
      social features that act as affordances. Further, this paper describes a feedback
      loop in which youth afforded opportunities to develop assets through contributing
      to their community in turn create affordances for additional youth and adults.

PMID- 29379455
TI  - Explicit Oral Narrative Intervention for Students with Williams Syndrome.
AB  - Narrative skills play a crucial role in organizing experience, facilitating
      social interaction and building academic discourse and literacy. They are at the
      interface of cognitive, social, and linguistic abilities related to school
      engagement. Despite their relative strengths in social and grammatical skills,
      students with Williams syndrome (WS) do not show parallel cognitive and pragmatic
      performance in narrative generation tasks. The aim of the present study was to
      assess retelling of a TV cartoon tale and the effect of an individualized
      explicit instruction of the narrative structure. Participants included eight
      students with WS who attended different special education levels. Narratives were
      elicited in two sessions (pre and post intervention), and were transcribed, coded
      and analyzed using the tools of the CHILDES Project. Narratives were coded for
      productivity and complexity at the microstructure and macrostructure levels.
      Microstructure productivity (i.e., length of narratives) included number of
      utterances, clauses, and tokens. Microstructure complexity included mean length
      of utterances, lexical diversity and use of discourse markers as cohesive
      devices. Narrative macrostructure was assessed for textual coherence through the
      Pragmatic Evaluation Protocol for Speech Corpora (PREP-CORP). Macrostructure
      productivity and complexity included, respectively, the recall and sequential
      order of scenarios, episodes, events and characters. A total of four intervention
      sessions, lasting approximately 20 min, were delivered individually once a week.
      This brief intervention addressed explicit instruction about the narrative
      structure and the use of specific discourse markers to improve cohesion of story
      retellings. Intervention strategies included verbal scaffolding and modeling,
      conversational context for retelling the story and visual support with pictures
      printed from the cartoon. Results showed significant changes in WS students'
      retelling of the story, both at macro- and microstructure levels, when assessed
      following a 2-week interval. Outcomes were better in microstructure than in
      macrostructure, where sequential order (i.e., complexity) did not show
      significant improvement. These findings are consistent with previous research
      supporting the use of explicit oral narrative intervention with participants who
      are at risk of school failure due to communication impairments. Discussion
      focuses on how assessment and explicit instruction of narrative skills might
      contribute to effective intervention programs enhancing school engagement in WS
      students.

PMID- 29379457
TI  - The Gaze-Cueing Effect in the United States and Japan: Influence of Cultural
      Differences in Cognitive Strategies on Control of Attention.
AB  - The direction of gaze automatically and exogenously guides visual spatial
      attention, a phenomenon termed as the gaze-cueing effect. Although this effect
      arises when the duration of stimulus onset asynchrony (SOA) between a non
      predictive gaze cue and the target is relatively long, no empirical research has
      examined the factors underlying this extended cueing effect. Two experiments
      compared the gaze-cueing effect at longer SOAs (700 ms) in Japanese and American
      participants. Cross-cultural studies on cognition suggest that Westerners tend to
      use a context-independent analytical strategy to process visual environments,
      whereas Asians use a context-dependent holistic approach. We hypothesized that
      Japanese participants would not demonstrate the gaze-cueing effect at longer SOAs
      because they are more sensitive to contextual information, such as the knowledge
      that the direction of a gaze is not predictive. Furthermore, we hypothesized that
      American participants would demonstrate the gaze-cueing effect at the long SOAs
      because they tend to follow gaze direction whether it is predictive or not. In
      Experiment 1, American participants demonstrated the gaze-cueing effect at the
      long SOA, indicating that their attention was driven by the central non
      predictive gaze direction regardless of the SOAs. In Experiment 2, Japanese
      participants demonstrated no gaze-cueing effect at the long SOA, suggesting that
      the Japanese participants exercised voluntary control of their attention, which
      inhibited the gaze-cueing effect with the long SOA. Our findings suggest that the
      control of visual spatial attention elicited by social stimuli systematically
      differs between American and Japanese individuals.

PMID- 29379458
TI  - Measurement Invariance of a Classroom Engagement Measure among Academically At
      Risk Students.
AB  - The current study investigated the measurement invariance of a classroom
      engagement measure across time points, genders, and ethnicities using a sample of
      523 academically at-risk students across grades 7 through 9; this measure was
      based on Skinner et al.'s (1990) original engagement measure. The engagement
      measure was comprised of 16 items, yielding three factors: Behavioral Engagement,
      Behavioral Disaffection, and Emotional Engagement. Configural, metric, and scalar
      invariance held across the three time points, as did invariance of factor
      covariances and means, indicating that scores have a similar meaning across all 3
      years. The engagement measure also featured adequate configural, metric, and
      scalar invariance, and invariance of factor covariances and means across genders
      and ethnicities. These findings suggest the measure is appropriate for
      investigating substantive hypotheses regarding classroom engagement across
      different grade levels, genders, and ethnicities. In summary, the current results
      indicate this measure of classroom engagement is suitable for testing hypotheses
      regarding group differences in engagement across grade levels, genders, and
      ethnicities. Researchers may also use this measure to examine relationships
      between the engagement factors and other important academic outcomes. Limitations
      of the current study, such as certain caveats regarding convergent validity and
      internal consistency, are also discussed.

PMID- 29379459
TI  - Why Numbers Are Embodied Concepts.

PMID- 29379460
TI  - What You Know, What You Do, and How You Feel: Cultural Competence, Cultural
      Consonance, and Psychological Distress.
AB  - Describing the link between culture (as a phenomenon pertaining to social
      aggregates) and the beliefs and behaviors of individuals has eluded satisfactory
      resolution; however, contemporary cognitive culture theory offers hope. In this
      theory, culture is conceptualized as cognitive models describing specific domains
      of life that are shared by members of a social group. It is sharing that gives
      culture its aggregate properties. There are two aspects to these cultural models
      at the level of the individual. Persons have their own representations of the
      world that correspond incompletely to the shared model-this is their 'cultural
      competence.' Persons are also variable in the degree to which they can put
      cultural models into practice in their own lives-this is their 'cultural
      consonance.' Low cultural consonance is a stressful experience and has been
      linked to higher psychological distress. The relationship of cultural competence
      per se and psychological distress is less clear. In the research reported here,
      cultural competence and cultural consonance are measured on the same sample and
      their associations with psychological distress are examined using multiple
      regression analysis. Results indicate that, with respect to psychological
      distress, while it is good to know the cultural model, it is better to put it
      into practice.

PMID- 29379461
TI  - The Effect of Language Learning Strategies on Proficiency, Attitudes and School
      Achievement.
AB  - This study examines language learning strategy (LLS) use in connexion with
      foreign language attitude, proficiency and general school achievement among lower
      secondary students in Years 5 and 8 (n = 868) in Hungary. An adapted version of
      the Strategies Inventory for Language Learning questionnaire was used for data
      collection. The results showed that Hungarian students mainly engage in
      metacognitive strategies in both years. Differences between more and less
      proficient language learners' strategy use have also been found. With regard to
      the effect of LLS on foreign language attitude, the foreign language mark and
      school achievement, path analysis indicated a good fit in both years. The
      metacognitive, social and memory strategies primarily influenced foreign language
      attitudes and marks in Year 5. The metacognitive strategies had a slight impact
      on school achievement as well as on foreign language marks. We demonstrated the
      dominant effect of metacognitive strategies and the low effect of memory
      strategies in Year 8. In addition, metacognitive strategies also influenced
      foreign language marks. The effect of foreign language marks on school
      achievement was also remarkable. There was a strong impact on the children's
      attitudes through these variables.

PMID- 29379462
TI  - Contributions of Motivation, Early Numeracy Skills, and Executive Functioning to
      Mathematical Performance. A Longitudinal Study.
AB  - The main goal of this longitudinal study is to examine the power of different
      variables and its dynamic interactions in predicting mathematical performance.
      The model proposed in this study includes indicators of motivational constructs
      (learning motivation and attributions), executive functioning (inhibition and
      working memory), and early numeracy skills (logical operations, counting, and
      magnitude comparison abilities), assessed during kindergarten, and mathematical
      performance in the second year of Primary Education. The sample consisted of 180
      subjects assessed in two moments (5-6 and 7-8 years old). The results showed an
      indirect effect of initial motivation on later mathematical performance.
      Executive functioning and early numeracy skills mediated the effect of motivation
      on later mathematic achievement. Practical implications of these findings for
      mathematics education are discussed.

PMID- 29379463
TI  - The Bulbocavernosus Reflex in the Differential Diagnosis of Multiple System
      Atrophy with Predominant Parkinsonism and Parkinson's Disease.
AB  - Multiple system atrophy with predominant parkinsonism (MSA-P) is a degenerative
      disorder that presents with autonomic dysfunction, atypical parkinsonism, and
      ataxia. Parkinson's disease (PD) is an age-related neurological disorder of the
      central nervous system. Differentiation between MSA-P and PD is important because
      treatments, complications, and prognoses differ. The bulbocavernosus reflex (BCR)
      tests the afferent and efferent signals of the pudendal nerve as well as the
      sacral cord. In this study, we investigated differences in BCR parameters between
      MSA-P and PD patients. Thirty-eight MSA-P patients and 32 PD patients were
      selected to participate in our electrophysiological investigations. The Keypoint
      EMG/EP system was used to induce the BCR, and latencies and amplitudes were
      recorded for systematic statistical analyses. Area under the curve of the
      receiver operating characteristic was used to assess the specificity and
      sensitivity of the BCR parameters. A BCR was elicited in 76.32% of MSA-P patients
      and 93.75% of PD patients. The BCR latencies of the MSA-P group were longer than
      those of the PD group (p < 0.001). In addition, the MSA-P group had a lower BCR
      amplitude compared to the PD and control groups (p < 0.001). We discovered the
      difference between MSA-P and PD through BCR latencies and amplitudes. Compared to
      PD patients, MSA-P patients have longer latencies and lower amplitudes.
      Therefore, the BCR may be used to discriminate between MSA-P and PD in some
      cases.

PMID- 29379464
TI  - Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their
      Correlation with Neurological Findings.
AB  - Objectives: To evaluate the function of the oculomotor and vestibular systems and
      to correlate these findings with the clinical status of patients with Gaucher
      disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was
      to find oculomotor biomarkers for future clinical trials. Methods: Twenty-six
      patients with GD3 were assessed for eligibility and 21 were able to perform at
      least one task. Horizontal and vertical reflexive saccades, smooth pursuit, gaze
      holding, optokinetic nystagmus, and horizontal vestibulo-ocular reflex (VOR) were
      examined by video-oculography/video-head impulse test and compared concurrently
      with 33 healthy controls. The Scale for the Assessment and Rating of Ataxia
      (SARA), the modified Severity Scoring Tool (mSST), and Grooved Pegboard Test
      (GPT) were administered to assess overall neurological function. Eleven patients
      were also re-assessed after 1 year. Results: Nine out of 17 patients exhibited
      gaze-holding deficits. One patient had upbeat nystagmus. Three patients presented
      with bilateral abducens palsy in combination with central oculomotor disorders,
      suggesting a bilateral involvement of the abducens nucleus. Horizontal angular
      VOR gain was reduced in all patients (0.66 +/- 0.37) compared with controls (1.1
      +/- 0.11, p < 0.001). Most strongly correlated with clinical rating scales were
      peak velocity of downward saccades (SARA: rho = -0.752, p < 0.0005; mSST: rho = 
      0.611, p = 0.003; GPT: rho = -0.649, p = 0.005) and duration of vertical saccades
      (SARA: rho = 0.806, p < 0.001; mSST: rho = 0.700, p < 0.0005; GPT: rho = 0.558, p
      = 0.02) together with the VOR gain (SARA: rho = -0.63, p = 0.016; mSST: rho = 
      0.725, p = 0.003; GPT: rho = -0.666, p = 0.004). Vertical smooth pursuit gain
      decreased significantly at follow-up. Interpretation: This study shows neuronal
      degeneration of the brainstem and cerebellum with combined involvement of both
      supranuclear and nuclear oculomotor structures and the vestibular system in GD3.
      We also identified oculomotor parameters that correlate with the neurological
      status and can be used as biomarkers in future clinical trials.

PMID- 29379465
TI  - Surface Electromyographic Examination of Poststroke Neuromuscular Changes in
      Proximal and Distal Muscles Using Clustering Index Analysis.
AB  - Whether stroke-induced paretic muscle changes vary across different distal and
      proximal muscles remains unclear. The objective of this study was to compare
      paretic muscle changes between a relatively proximal muscle (the biceps brachii
      muscle) and two distal muscles (the first dorsal interosseous muscle and the
      abductor pollicis brevis muscle) following hemisphere stroke using clustering
      index (CI) analysis of surface electromyograms (EMGs). For each muscle, surface
      EMG signals were recorded from the paretic and contralateral sides of 12 stroke
      subjects versus the dominant side of eight control subjects during isometric
      muscle contractions to measure the consequence of graded levels of contraction
      (from a mild level to the maximal voluntary contraction). Across all examined
      muscles, it was found that partial paretic muscles had abnormally higher or lower
      CI values than those of the healthy control muscles, which exhibited a
      significantly larger variance in the CI via a series of homogeneity of variance
      tests (p < 0.05). This finding indicated that both neurogenic and myopathic
      changes were likely to take place in paretic muscles. When examining two distal
      muscles of individual stroke subjects, relatively consistent CI abnormalities
      (toward neuropathy or myopathy) were observed. By contrast, consistency in CI
      abnormalities were not found when comparing proximal and distal muscles,
      indicating differences in motor unit alternation between the proximal and distal
      muscles on the paretic sides of stroke survivors. Furthermore, CI abnormalities
      were also observed for all three muscles on the contralateral side. Our findings
      help elucidate the pathological mechanisms underlying stroke sequels, which might
      prove useful in developing improved stroke rehabilitation protocols.

PMID- 29379466
TI  - Sleep-Disordered Breathing in People with Multiple Sclerosis: Prevalence,
      Pathophysiological Mechanisms, and Disease Consequences.
AB  - Sleep problems are common in people with multiple sclerosis (MS). Reported
      prevalence rates of sleep-disordered breathing (SDB) vary between 0 and 87%.
      Differences in recruitment procedures and study designs likely contribute to the
      wide variance in reported prevalence rates of SBD in MS. This can make attempts
      to compare SDB rates in people with MS to the general population challenging.
      Little is known about the pathophysiological mechanisms that contribute to SDB in
      people with MS or whether MS contributes to SDB disease progression. However,
      compared to the general obstructive sleep apnea (OSA) population, there are clear
      differences in the clinical phenotypes of SDB in the MS population. For instance
      they are typically not obese and rates of SDB are often comparable or higher to
      the general population, despite the high female predominance of MS. Thus, the
      risk factors and pathophysiological causes of SDB in people with MS are likely to
      be different compared to people with OSA who do not have MS. There may be
      important bidirectional relationships between SDB and MS. Demyelinating lesions
      of MS in the brain stem and spinal cord could influence breathing control and
      upper airway muscle activity to cause SDB. Intermittent hypoxia caused by apneas
      during the night can increase oxidative stress and may worsen neurodegeneration
      in people with MS. In addition, inflammation and changes in cytokine levels may
      play a key role in the relationship between SDB and MS and their shared
      consequences. Indeed, fatigue, neurocognitive dysfunction, and depression may
      worsen considerably if both disorders coexist. Recent studies indicate that
      treatment of SDB in people with MS with conventional first-line therapy,
      continuous positive airway pressure therapy, can reduce fatigue and cognitive
      impairment. However, if the causes of SDB differ in people with MS, so too may
      the optimal therapy. Thus, many questions remain concerning the relationship
      between these two disorders and the underlying mechanisms and shared
      consequences. Improved understanding of these factors has the potential to unlock
      new therapeutic targets.

PMID- 29379467
TI  - Health-Related Quality of Life Is Severely Affected in Primary Orthostatic
      Tremor.
AB  - Background: Primary orthostatic tremor (POT) is a movement disorder characterized
      by unsteadiness upon standing still due to a tremor affecting the legs. It is a
      gradually progressive condition with limited treatment options. Impairments in
      health-related quality of life (HQoL) seem to far exceed the physical disability
      associated with the condition. Methods: A multi-center, mixed-methodology study
      was undertaken to investigate 40 consecutive patients presenting with POT to four
      movement disorder centers in France. HQoL was investigated using eight
      quantitative scales and a qualitative study which employed semi-structured
      interviews. Qualitative data were analyzed with a combination of grounded-theory
      approach. Results: Our results confirm that HQoL in POT is severely affected.
      Fear of falling was identified as the main predictor of HQoL. The qualitative arm
      of our study explored our initial results in greater depth and uncovered themes
      not identified by the quantitative approach. Conclusion: Our results illustrate
      the huge potential of mixed methodology in identifying issues influencing HQoL in
      POT. Our work paves the way for enhanced patient care and improved HQoL in POT
      and is paradigmatic of this modern approach for investigating HQoL issues in
      chronic neurological disorders.

PMID- 29379468
TI  - Advances in Radiotherapy for Glioblastoma.
AB  - External beam radiotherapy (RT) has long played a crucial role in the treatment
      of glioblastoma. Over the past several decades, significant advances in RT
      treatment and image-guidance technology have led to enormous improvements in the
      ability to optimize definitive and salvage treatments. This review highlights
      several of the latest developments and controversies related to RT, including the
      treatment of elderly patients, who continue to be a fragile and vulnerable
      population; potential salvage options for recurrent disease including
      reirradiation with chemotherapy; the latest imaging techniques allowing for more
      accurate and precise delineation of treatment volumes to maximize the therapeutic
      ratio of conformal RT; the ongoing preclinical and clinical data regarding the
      combination of immunotherapy with RT; and the increasing evidence of cancer stem
      cell niches in the subventricular zone which may provide a potential target for
      local therapies. Finally, continued development on many fronts have allowed for
      modestly improved outcomes while at the same time limiting toxicity.

PMID- 29379469
TI  - Extensive Delayed Brain Atrophy after Resuscitation in a Patient with Multiple
      System Atrophy.
AB  - Brain magnetic resonance imaging (MRI) of multiple system atrophy (MSA) shows
      atrophy in the cerebrum, cerebellum, and brainstem. It is also characterized by
      specific patterns such as hyperintense lateral putaminal rim. MRI of hypoxic
      encephalopathy shows atrophy mainly in the gray matter, and laminar necrosis in
      the cerebral cortex is often observed. Here, we report an MSA patient damaged by
      hypoxic insult and resuscitated after 18-min cardiac arrest. The brain of the
      patient developed severe atrophy within a period of 10 months. Furthermore, brain
      atrophy was observed in the white and gray matter, which preserved the brain
      atrophy pattern in MSA. We assume that alpha-synuclein oligomerization is
      involved in the neural cell death and brain atrophy. It might have caused further
      neural cell death in the brain damaged by hypoxia. Alpha-synuclein, which is
      involved in the pathogenesis of MSA, is suggested to be a prion. Misfolded alpha
      synuclein may propagate through cell-to-cell transmission and cause wide
      pathological change, visible as atrophied MR imaging.

PMID- 29379470
TI  - Mechanistic Insights into Regulation of JAK2 Tyrosine Kinase.
AB  - JAK2 is a member of the Janus kinase (JAKs) family of non-receptor protein
      tyrosine kinases, which includes JAK1-3 and TYK2. JAKs serve as the cytoplasmic
      signaling components of cytokine receptors and are activated through cytokine
      mediated trans-phosphorylation, which leads to receptor phosphorylation and
      recruitment and phosphorylation of signal transducer and activator of
      transcription (STAT) proteins. JAKs are unique among tyrosine kinases in that
      they possess a pseudokinase domain, which is just upstream of the C-terminal
      tyrosine kinase domain. A wealth of biochemical and clinical data have
      established that the pseudokinase domain of JAKs is crucial for maintaining a low
      basal (absence of cytokine) level of tyrosine kinase activity. In particular,
      gain-of-function mutations in the JAK genes, most frequently, V617F in the
      pseudokinase domain of JAK2, have been mapped in patients with blood disorders,
      including myeloproliferative neoplasms and leukemias. Recent structural and
      biochemical studies have begun to decipher the molecular mechanisms that maintain
      the basal, low-activity state of JAKs and that, via mutation, lead to
      constitutive activity and disease. This review will examine these mechanisms and
      describe how this knowledge could potentially inform drug development efforts
      aimed at obtaining a mutant (V617F)-selective inhibitor of JAK2.

PMID- 29379471
TI  - Drought-Tolerant Plant Growth-Promoting Rhizobacteria Associated with Foxtail
      Millet in a Semi-arid Agroecosystem and Their Potential in Alleviating Drought
      Stress.
AB  - The application of plant growth promoting rhizobacteria (PGPR) to agro-ecosystems
      is considered to have the potential for improving plant growth in extreme
      environments featured by water shortage. Herein, we isolated bacterial strains
      from foxtail millet (Setaria italica L.), a drought-tolerant crop cultivated in
      semiarid regions in the northeast of China. Four isolates were initially selected
      for their ability to produce ACC deaminase as well as drought tolerance. The
      isolates were identified as Pseudomonas fluorescens, Enterobacter hormaechei, and
      Pseudomonas migulae on the basis of 16S rRNA sequence analysis. All of these
      drought-tolerant isolates were able to produce EPS (exopolysaccharide).
      Inoculation with these strains stimulated seed germination and seedling growth
      under drought stress. Pseudomonas fluorescens DR7 showed the highest level of ACC
      deaminase and EPS-producing activity. DR7 could efficiently colonize the root
      adhering soil, increased soil moisture, and enhance the root adhering soil/root
      tissue ratio. These results suggest drought tolerant PGPR from foxtail millet
      could enhance plant growth under drought stress conditions and serve as effective
      bioinoculants to sustain agricultural production in arid regions.

PMID- 29379472
TI  - Caenorhabditis elegans Predation on Bacillus anthracis: Decontamination of Spore
      Contaminated Soil with Germinants and Nematodes.
AB  - Remediation of Bacillus anthracis-contaminated soil is challenging and approaches
      to reduce overall spore levels in environmentally contaminated soil or after
      intentional release of the infectious disease agent in a safe, low-cost manner
      are needed. B. anthracis spores are highly resistant to biocides, but once
      germinated they become susceptible to traditional biocides or potentially even
      natural predators such as nematodes in the soil environment. Here, we describe a
      two-step approach to reducing B. anthracis spore load in soil during laboratory
      trials, whereby germinants and Caenorhabditis elegans nematodes are applied
      concurrently. While the application of germinants reduced B. anthracis spore load
      by up to four logs depending on soil type, the addition of nematodes achieved a
      further log reduction in spore count. These laboratory based results suggest that
      the combined use of nematodes and germinants could represent a promising approach
      for the remediation of B. anthracis spore contaminated soil. Originality
      Significance Statement: This study demonstrates for the first time the successful
      use of environmentally friendly decontamination methods to inactivate Bacillus
      anthracis spores in soil using natural predators of the bacterium, nematode
      worms.

PMID- 29379473
TI  - The Inner Workings of the Outer Surface: Skin and Gill Microbiota as Indicators
      of Changing Gut Health in Yellowtail Kingfish.
AB  - The mucosal surfaces and associated microbiota of fish are an important primary
      barrier and provide the first line of defense against potential pathogens. An
      understanding of the skin and gill microbial assemblages and the factors which
      drive their composition may provide useful insights into the broad dynamics of
      fish host-microbial relationships, and may reveal underlying changes in health
      status. This is particularly pertinent to cultivated systems whereby various
      stressors may led to conditions (like enteritis) which impinge on productivity.
      As an economically important species, we assessed whether the outer-surface
      bacterial communities reflect a change in gut health status of cultivated
      Yellowtail Kingfish (Seriola lalandi). Active bacterial assemblages were surveyed
      from RNA extracts from swabs of the skin and gills by constructing Illumina 16S
      rRNA gene amplicon libraries. Proteobacteria and Bacteroidetes were predominant
      in both the skin and gills, with enrichment of key beta-proteobacteria in the
      gills (Nitrosomonadales and Ferrovales). Fish exhibiting early stage chronic
      lymphocytic enteritis comprised markedly different global bacterial assemblages
      compared to those deemed healthy and exhibiting late stages of the disease. This
      corresponded to an overall loss of diversity and enrichment of Proteobacteria and
      Actinobacteria, particularly in the gills. In contrast, bacterial assemblages of
      fish with late stage enteritis were generally similar to those of healthy
      individuals, though with some distinct taxa. In conclusion, gut health status is
      an important factor which defines the skin and gill bacterial assemblages of fish
      and likely reflects changes in immune states and barrier systems during the early
      onset of conditions like enteritis. This study represents the first to
      investigate the microbiota of the outer mucosal surfaces of fish in response to
      underlying chronic gut enteritis, revealing potential biomarkers for assessing
      fish health in commercial aquaculture systems.

PMID- 29379474
TI  - Dynamics of Viral and Host Immune Cell MicroRNA Expression during Acute
      Infectious Mononucleosis.
AB  - Epstein-Barr virus (EBV) is the etiological agent of acute infectious
      mononucleosis (IM). Since acute IM is a self-resolving disease with most patients
      regaining health in 1-3 weeks there have been few studies examining molecular
      signatures in early acute stages of the disease. MicroRNAs (miRNAs) have been
      shown, however, to influence immune cell function and consequently the generation
      of antibody responses in IM. In this study, we performed a comprehensive analysis
      of differentially expressed miRNAs in early stage uncomplicated acute IM. miRNAs
      were profiled from patient peripheral blood obtained at the time of IM diagnosis
      and at subsequent time points, and pathway analysis performed to identify
      important immune and cell signaling pathways. We identified 215 differentially
      regulated miRNAs at the most acute stage of infection when the patients initially
      sought medical help. The number of differentially expressed miRNAs decreased to
      148 and 68 at 1 and 2 months post-primary infection, with no significantly
      changed miRNAs identified at 7 months post-infection. Interferon signaling, T and
      B cell signaling and antigen presentation were the top pathways influenced by the
      miRNAs associated with IM. Thus, a dynamic and regulated expression profile of
      miRNA accompanies the early acute immune response, and resolution of infection,
      in IM.

PMID- 29379475
TI  - Comparative Proteomic Analysis of Hymenolepis diminuta Cysticercoid and Adult
      Stages.
AB  - Cestodiases are common parasitic diseases of animals and humans. As cestodes have
      complex lifecycles, hexacanth larvae, metacestodes (including cysticercoids), and
      adults produce proteins allowing them to establish invasion and to survive in the
      hostile environment of the host. Hymenolepis diminuta is the most commonly used
      model cestode in experimental parasitology. The aims of the present study were to
      perform a comparative proteomic analysis of two consecutive developmental stages
      of H. diminuta (cysticercoid and adult) and to distinguish proteins which might
      be characteristic for each of the stages from those shared by both stages.
      Somatic proteins of H. diminuta were isolated from 6-week-old cysticercoids and
      adult tapeworms. Cysticercoids were obtained from experimentally infected
      beetles, Tenebrio molitor, whereas adult worms were collected from experimentally
      infected rats. Proteins were separated by GeLC-MS/MS (one dimensional gel
      electrophoresis coupled with liquid chromatography and tandem mass spectrometry).
      Additionally protein samples were digested in-liquid and identified by LC-MS/MS.
      The identified proteins were classified according to molecular function, cellular
      components and biological processes. Our study showed a number of differences and
      similarities in the protein profiles of cysticercoids and adults; 233
      cysticercoid and 182 adult proteins were identified. From these proteins, 131
      were present only in the cysticercoid and 80 only in the adult stage samples.
      Both developmental stages shared 102 proteins; among which six represented
      immunomodulators and one is a potential drug target. In-liquid digestion and LC
      MS/MS complemented and confirmed some of the GeLC-MS/MS identifications. Possible
      roles and functions of proteins identified with both proteomic approaches are
      discussed.

PMID- 29379476
TI  - Effect of Various Inoculum Levels of Multidrug-Resistant Salmonella enterica
      Serovar Heidelberg (2011 Ground Turkey Outbreak Isolate) on Cecal Colonization,
      Dissemination to Internal Organs, and Deposition in Skeletal Muscles of
      Commercial Turkeys after Experimental Oral Challenge.
AB  - Salmonella enterica serovar Heidelberg (S. Heidelberg) is a major foodborne
      pathogen colonizing poultry. The pathogen is associated with a significant number
      of foodborne outbreaks through contaminated poultry meat, including turkeys.
      Recently, multidrug-resistant (MDR) strains of S. Heidelberg have emerged as a
      threat to human public health in the United States. The objective of this study
      was to determine the cecal colonization, dissemination to internal organs, and
      the potential for skeletal muscle deposition of an MDR S. Heidelberg isolate from
      the 2011 ground turkey outbreak in the United States after the experimental oral
      challenge of poults (young turkeys) and adult turkey hens. In the poult study,
      two separate experiments using day-old, straight-run, commercial hybrid converter
      poults were randomly assigned to five challenge groups (0, 10?2, 10?4, 10?6, 10?8
      CFU groups; 12 poults/group; N = 60/experiment) and a week after, treatment
      groups were challenged separately with 0-, 2-, 4-, 6-, and 8- log10 CFU of S.
      Heidelberg orally. After 14 days post-challenge, the poults were euthanized, and
      samples were collected to determine MDR S. Heidelberg colonization in the cecum,
      dissemination to liver and spleen, and deposition in the thigh, drumstick, and
      breast muscles. A similar experimental design was followed for the adult turkey
      hens. In two separate experiments, 11-week-old commercial Hybrid Converter turkey
      hens (4 hens/group; N = 20/experiment) were challenged with MDR S. Heidelberg and
      on day 16 post-challenge, birds were euthanized and samples were collected to
      determine Salmonella populations in the samples. The results indicated that, in
      turkey poults, the recovery of MDR S. Heidelberg was highest in the cecum
      followed by spleen, liver, thigh, drumstick, and breast. All tested inoculum
      levels resulted in more than 3.5 log10 CFU/g colonization in the poult cecum. The
      cecal colonization, dissemination to internal organs, and tissue deposition of
      MDR S. Heidelberg were high in poults. The pathogen recovery from the cecum of
      adult turkey hens ranged from 37.5 to 62.5% in the challenge groups. The results
      signify the importance of controlling MDR S. Heidelberg in turkeys at the farm
      level to improve the safety of turkey products.

PMID- 29379477
TI  - Ultrastructural Analysis of Cell Envelope and Accumulation of Lipid Inclusions in
      Clinical Mycobacterium tuberculosis Isolates from Sputum, Oxidative Stress, and
      Iron Deficiency.
AB  - Introduction: Mycobacteria have several unique cellular characteristics, such as
      multiple cell envelope layers, elongation at cell poles, asymmetric cell
      division, and accumulation of intracytoplasmic lipid inclusions, which
      contributes to their survival under stress conditions. However, the understanding
      of these characteristics in clinical Mycobacterium tuberculosis (M. tuberculosis)
      isolates and under host stress is limited. We previously reported the influence
      of host stress on the cell length distribution in a large set of clinical M.
      tuberculosis isolates (n = 158). Here, we investigate the influence of host
      stress on the cellular ultrastructure of few clinical M. tuberculosis isolates (n
      = 8) from that study. The purpose of this study is to further understand the
      influence of host stress on the cellular adaptations of clinical M. tuberculosis
      isolates. Methods: We selected few M. tuberculosis isolates (n = 8) for analyzing
      the cellular ultrastructure ex vivo in sputum and under in vitro stress
      conditions by transmission electron microscopy. The cellular adaptations of M.
      tuberculosis in sputum were correlated with the ultrastructure of antibiotic
      sensitive and resistant isolates in liquid culture, under oxidative stress, iron
      deficiency, and exposure to isoniazid. Results: In sputum, M. tuberculosis
      accumulated intracytoplasmic lipid inclusions. In liquid culture, clinical M.
      tuberculosis revealed isolate to isolate variation in the extent of
      intracytoplasmic lipid inclusions, which were absent in the laboratory strain
      H37Rv. Oxidative stress, iron deficiency, and exposure to isoniazid increased the
      accumulation of lipid inclusions and decreased the thickness of the cell envelope
      electron transparent layer in M. tuberculosis cells. Furthermore,
      intracytoplasmic compartments were observed in iron deficient cells. Conclusion:
      Our ultrastructural analysis has revealed significant influence of host stress on
      the cellular adaptations in clinical M. tuberculosis isolates. These adaptations
      may contribute to the survival of M. tuberculosis under host and antibiotic
      stress conditions. Variation in the cellular adaptations among clinical M.
      tuberculosis isolates may correlate with their ability to persist in tuberculosis
      patients during antibiotic treatment. These observations indicate the need for
      further analyzing these cellular adaptations in a large set of clinical M.
      tuberculosis isolates. This will help to determine the significance of these
      cellular adaptations in the tuberculosis treatment.

PMID- 29379479
TI  - How Does HTLV-1 Undergo Oncogene-Dependent Replication Despite a Strong Immune
      Response?
AB  - In 1987, Mitsuaki Yoshida proposed the following model (Yoshida and Seiki, 1987):
      "... T-cells activated through the endogenous p40x would express viral antigens
      including the envelope glycoproteins which are exposed on the cell surface. These
      glycoproteins are targets of host immune surveillance, as is evidenced by the
      cytotoxic effects of anti-envelope antibodies or patient sera. Eventually all
      cells expressing the viral antigens, that is, all cells driven by the p40x would
      be rejected by the host. Only those cells that did not express the viral antigens
      would survive. Later, these antigen-negative infected cells would begin again to
      express viral antigens, including p40x, thus entering into the second cycle of
      cell propagation. These cycles would be repeated in so-called healthy virus
      carriers for 20 or 30 years or longer...." Three decades later, accumulated
      experimental facts particularly on intermittent viral transcription and
      regulation by the host immune response appear to prove that Yoshida was right.
      This Hypothesis and Theory summarizes the evidences that support this paradigm.

PMID- 29379480
TI  - Family Aggregation of HTLV-1 Infection Associated with FAS -670A/G Polymorphism:
      A Case Report.
AB  - Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with ATL and
      inflammatory diseases but remains a neglected health problem. HTLV-1 associated
      diseases were originally described as sporadic entities, but family aggregations
      have been reported. Viral, genetic, immunological and behavioral factors were
      used to explain family clusters, but until now a clear explanation remains
      uncertain. In the present study we report, for the first time, a family cluster
      of diseased persons presenting the infection across three generations associated
      with FAS -670A/G polymorphism.

PMID- 29379478
TI  - Arginine and Polyamines Fate in Leishmania Infection.
AB  - Leishmania is a protozoan parasite that alternates its life cycle between the
      sand fly and the mammalian host macrophages, involving several environmental
      changes. The parasite responds to these changes by promoting a rapid metabolic
      adaptation through cellular signaling modifications that lead to transcriptional
      and post-transcriptional gene expression regulation and morphological
      modifications. Molecular approaches such as gene expression regulation, next
      generation sequencing (NGS), microRNA (miRNA) expression profiling, in cell
      Western blot analyses and enzymatic activity profiling, have been used to
      characterize the infection of murine BALB/c and C57BL/6 macrophages, as well as
      the human monocytic cell-lineage THP-1, with Leishmania amazonensis wild type (La
      WT) or arginase knockout (La-arg - ). These models are being used to elucidate
      physiological roles of arginine and polyamines pathways and the importance of
      arginase for the establishment of the infection. In this review, we will describe
      the main aspects of Leishmania-host interaction, focusing on the arginine and
      polyamines pathways and pointing to possible targets to be used for prognosis
      and/or in the control of the infection. The parasite enzymes, arginase and nitric
      oxide synthase-like, have essential roles in the parasite survival and in the
      maintenance of infection. On the other hand, in mammalian macrophages, defense
      mechanisms are activated inducing alterations in the mRNA, miRNA and enzymatic
      profiles that lead to the control of infection. Furthermore, the genetic
      background of both parasite and host are also important to define the fate of
      infection.

PMID- 29379482
TI  - Streptococcus pneumoniae Proteins AmiA, AliA, and AliB Bind Peptides Found in
      Ribosomal Proteins of Other Bacterial Species.
AB  - The nasopharynx is frequently colonized by both commensal and pathogenic bacteria
      including Streptococcus pneumoniae (pneumococcus). Pneumococcus is an important
      pathogen responsible for bacterial meningitis and community acquired pneumonia
      but is also commonly an asymptomatic colonizer of the nasopharynx. Understanding
      interactions between microbes may provide insights into pathogenesis. Here, we
      investigated the ability of the three oligopeptide-binding proteins AmiA, AliA,
      and AliB of an ATP-binding cassette transporter of pneumococcus to detect short
      peptides found in other bacterial species. We found three possible peptide
      ligands for AmiA and four each for AliA and AliB of which two for each protein
      matched ribosomal proteins of other bacterial species. Using synthetic peptides
      we confirmed the following binding: AmiA binds peptide AKTIKITQTR, matching 50S
      ribosomal subunit protein L30, AliA binds peptide FNEMQPIVDRQ, matching 30S
      ribosomal protein S20, and AliB binds peptide AIQSEKARKHN, matching 30S ribosomal
      protein S20, without excluding the possibility of binding of the other peptides.
      These Ami-AliA/AliB peptide ligands are found in multiple species in the class of
      Gammaproteobacteria which includes common colonizers of the nostrils and
      nasopharynx. Binding such peptides may enable pneumococcus to detect and respond
      to neighboring species in its environment and is a potential mechanism for
      interspecies communication and environmental surveillance.

PMID- 29379481
TI  - Hijacking of the AP-1 Signaling Pathway during Development of ATL.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a fatal
      malignancy known as adult T-cell leukemia (ATL). One way to address the pathology
      of the disease lies on conducting research with a molecular approach. In addition
      to the analysis of ATL-relevant signaling pathways, understanding the regulation
      of important and relevant transcription factors allows researchers to reach this
      fundamental objective. HTLV-1 encodes for two oncoproteins, Tax and HTLV-1 basic
      leucine-zipper factor, which play significant roles in the cellular
      transformation and the activation of the host's immune responses. Activating
      protein-1 (AP-1) transcription factor has been linked to cancer and neoplastic
      transformation ever since the first representative members of the Jun and Fos
      gene family were cloned and shown to be cellular homologs of viral oncogenes. AP
      1 is a dimeric transcription factor composed of proteins belonging to the Jun (c
      Jun, JunB, and JunD), Fos (c-Fos, FosB, Fra1, and Fra2), and activating
      transcription factor protein families. Activation of AP-1 transcription factor
      family by different stimuli, such as inflammatory cytokines, stress inducers, or
      pathogens, results in innate and adaptive immunity. AP-1 is also involved in
      various cellular events including differentiation, proliferation, survival, and
      apoptosis. Deregulated expression of AP-1 transcription factors is implicated in
      various lymphomas such as classical Hodgkin lymphomas, anaplastic large cell
      lymphomas, diffuse large B-cell lymphomas, and adult T-cell leukemia. Here, we
      review the current thinking behind deregulation of the AP-1 pathway and its
      contribution to HTLV-induced cellular transformation.

PMID- 29379483
TI  - Virulence and Stress Responses of Shigella flexneri Regulated by PhoP/PhoQ.
AB  - The two-component signal transduction system PhoP/PhoQ is an important regulator
      for stress responses and virulence in most Gram-negative bacteria, but
      characterization of PhoP/PhoQ in Shigella has not been thoroughly investigated.
      In the present study, we found that deletion of phoPQ (DeltaphoPQ) from Shigella
      flexneri 2a 301 (Sf301) resulted in a significant decline (reduced by more than
      15-fold) in invasion of HeLa cells and Caco-2 cells, and less inflammation (- or
      +) compared to Sf301 (+++) in the guinea pig Sereny test. In low Mg2+ (10 MUM)
      medium or pH 5 medium, the DeltaphoPQ strain exhibited a growth deficiency
      compared to Sf301. The DeltaphoPQ strain was more sensitive than Sf301 to
      polymyxin B, an important antimicrobial agent for treating multi-resistant Gram
      negative infections. By comparing the transcriptional profiles of DeltaphoPQ and
      Sf301 using DNA microarrays, 117 differentially expressed genes (DEGs) were
      identified, which were involved in Mg2+ transport, lipopolysaccharide
      modification, acid resistance, bacterial virulence, respiratory, and energy
      metabolism. Based on the reported PhoP box motif [(T/G) GTTTA-5nt-(T/G) GTTTA],
      we screened 38 suspected PhoP target operons in S. flexneri, and 11 of them
      (phoPQ, mgtA, slyB, yoaE, yrbL, icsA, yhiWX, rstA, hdeAB, pagP, and shf-rfbU-virK
      msbB2) were demonstrated to be PhoP-regulated genes based on electrophoretic
      mobility shift assays and beta-galactosidase assays. One of these PhoP-regulated
      genes, icsA, is a well-known virulence factor in S. flexneri. In conclusion, our
      data suggest that the PhoP/PhoQ system modulates S. flexneri virulence (in an
      icsA-dependent manner) and stress responses of Mg2+, pH and antibacterial
      peptides.

PMID- 29379484
TI  - PmrA/PmrB Two-Component System Regulation of lipA Expression in Pseudomonas
      aeruginosa PAO1.
AB  - Pseudomonas lipases are well-studied, but few studies have examined the
      mechanisms of lipase expression regulation. As a global regulatory protein, PmrA
      controls the expression of multiple genes such as the Dot/Icm apparatus,
      eukaryotic-like proteins, and secreted effectors. In this study, the effect of
      PmrA on expression of the lipase lipA in Pseudomonas aeruginosa PAO1 was
      investigated by knocking out or overexpressing pmrA, rsmY, and rsmA. PmrA
      regulated the expression of lipA at both the transcriptional and translational
      level although translation was the pivotal regulatory mechanism for lipA
      expression. PmrA also regulated the expression of rsmY. Using gel mobility shift
      assay and pmrA/rsmY double gene knock-out model, we showed that PmrA directly
      bound to the promoter sequence of rsmY to regulate lipA expression. Translation
      of lipA was activated by the PmrA/PmrB system via RsmA. Specifically, the Shine
      Dalgarno (SD) sequence located at lipA mRNA was overlapped through combination
      between RsmA and the AGAUGA sequence, subsequently blocking the 30S ribosomal
      subunit to the SD sequence, leading to translational inhibition of lipA.
      Transcriptional repression of RsmY initiated translation of lipA through negative
      translational regulation of rsmA. In conclusion, this study demonstrated that in
      P. aeruginosa PAO1, PmrA mainly regulated rsmY expression at a translational
      level to influence lipA expression. RsmY primarily activated lipA translation via
      negative translational regulation of rsmA.

PMID- 29379485
TI  - Endogenous Retrovirus 3 - History, Physiology, and Pathology.
AB  - Endogenous viral elements (EVE) seem to be present in all eukaryotic genomes. The
      composition of EVE varies between different species. The endogenous retrovirus 3
      (ERV3) is one of these elements that is present only in humans and other
      Catarrhini. Conservation of ERV3 in most of the investigated Catarrhini and the
      expression pattern in normal tissues suggest a putative physiological role of
      ERV3. On the other hand, ERV3 has been implicated in the pathogenesis of auto
      immunity and cancer. In the present review we summarize knowledge about this
      interesting EVE. We propose the model that expression of ERV3 (and probably other
      EVE loci) under pathological conditions might be part of a metazoan SOS response.

PMID- 29379487
TI  - RNase III-Binding-mRNAs Revealed Novel Complementary Transcripts in Streptomyces.
AB  - cis-Antisense RNAs (asRNAs) provide very simple and effective gene expression
      control due to the perfect complementarity between regulated and regulatory
      transcripts. In Streptomyces, the antibiotic-producing clade, the antisense
      control system is not yet understood, although it might direct the organism's
      complex development. Initial studies in Streptomyces have found a number of
      asRNAs. Apart from this, hundreds of mRNAs have been shown to bind RNase III, the
      double strand-specific endoribonuclease. In this study, we tested 17 mRNAs that
      have been previously co-precipitated with RNase III for antisense expression. Our
      RACE mapping showed that all of these mRNAs possess cognate asRNA. Additional
      tests for antisense expression uncovered as-adpA, as-rnc, as3983, as-sigB, as
      sigH, and as-sigR RNAs. Northern blots detected the expression profiles of 18
      novel transcripts. Noteworthy, we also found that only a minority of asRNAs
      respond to the absence of RNase III enzyme by increasing their cellular levels.
      Our findings suggest that antisense expression is widespread in Streptomyces,
      including genes of such important developmental regulators, as AdpA, RNase III,
      and sigma factors.

PMID- 29379486
TI  - Designing a B Cell-Based Vaccine against a Highly Variable Hepatitis C Virus.
AB  - The ability to use structure-based design and engineering to control the
      molecular shape and reactivity of an immunogen to induce protective responses
      shows great promise, along with corresponding advancements in vaccine testing and
      evaluation systems. We describe in this review new paradigms for the development
      of a B cell-based HCV vaccine. Advances in test systems to measure in vitro and
      in vivo antibody-mediated virus neutralization include retroviral pseudotype
      particles expressing HCV E1E2 glycoproteins (HCVpp), infectious cell culture
      derived HCV virions (HCVcc), and surrogate animal models mimicking acute HCV
      infection. Their applications have established the role of broadly neutralizing
      antibodies to control HCV infection. However, the virus has immunogenic regions
      in the viral envelope glycoproteins that are associated with viral escape or non
      neutralizing antibodies. These regions serve as immunologic decoys that divert
      the antibody response from less prominent conserved regions mediating virus
      neutralization. This review outlines the immunogenic regions on E2, which are
      roughly segregated into the hypervariable region 1 (HVR1), and five clusters of
      overlapping epitopes designated as antigenic domains A-E. Understanding the
      molecular architecture of conserved neutralizing epitopes within these antigenic
      domains, and how other antigenic regions or decoys deflect the immune response
      from these conserved regions will provide a roadmap for the rational design of an
      HCV vaccine.

PMID- 29379488
TI  - Prevalence, Virulence Genes and Antimicrobial Resistance Profiles of Salmonella
      Serovars from Retail Beef in Selangor, Malaysia.
AB  - The aim of the present study was to investigate the prevalence of Salmonella
      spp., Salmonella Enteritidis and Salmonella Typhimurium in retail beef from
      different retail markets of Selangor area, as well as, to assess their pathogenic
      potential and antimicrobial resistance. A total of 240 retail beef meat samples
      (chuck = 60; rib = 60; round = 60; sirloin = 60) were randomly collected. The
      multiplex polymerase chain reaction (mPCR) in combination with the most probable
      number (MPN) method was employed to detect Salmonella spp., S. Enteritidis and S.
      Typhimurium in the meat samples. The prevalence of Salmonella spp., S.
      Enteritidis and S. Typhimurium in 240 beef meat samples were 7.50, 1.25, and
      0.83%, respectively. The microbial loads of total Salmonella was found in the
      range of <3 to 15 MPN/g. Eight different serovars of Salmonella were identified
      among the 23 isolates, and S. Agona was the predominant serovar (26.09%).
      Interestingly, all the Salmonella isolates were resistant to penicillin,
      erythromycin and vancomycin, but the sensitivity was observed for tetracycline,
      gentamicin and amoxicillin/clavulanic acid. All 23 isolates were resistant to at
      least three antibiotics. Two S. Typhimurium isolates (8.70%) exhibited the
      highest multiple antibiotic resistance (MAR) index value of 0.56 which shown
      resistance to nine antibiotics. PCR analysis of virulence genes showed that all
      Salmonella isolates (100%) were positive for the invA gene. Meanwhile, pefA was
      only identified in S. Enteritidis and S. Typhimurium. The findings in this study
      indicate that retail beef products tested were widely contaminated with multi
      drug resistant (MDR) Salmonella and various virulence genes are present among the
      isolated Salmonella serovars.

PMID- 29379489
TI  - Effects of Sub-lethal Concentrations of Silver Nanoparticles on a Simulated
      Intestinal Prokaryotic-Eukaryotic Interface.
AB  - Nanotechnology applications are expected to bring a range of benefits to the food
      sector, aiming to provide better quality and conservation. In this research, the
      physiological response of both an Escherichia coli mono-species biofilm and Caco
      2 intestinal cells to sub-lethal concentrations of silver nanoparticles (AgNPs)
      has been investigated. In order to simulate the anaerobic and aerobic
      compartments required for bacteria and intestinal cells growth, a simplified semi
      batch model based on a transwell permeable support was developed. Interaction
      between the two compartments was obtained by exposing Caco-2 intestinal cells to
      the metabolites secreted by E. coli biofilm after its exposure to AgNPs. To the
      best of the authors' knowledge, this study is the first to investigate the effect
      of AgNPs on Caco-2 cells that takes into consideration previous AgNP-intestinal
      biofilm interactions, and at concentrations mimicking real human exposure. Our
      data show that 1 MUg/mL AgNPs in anaerobic conditions (i) promote biofilm
      formation up to 2.3 +/- 0.3 fold in the first 72 h of treatment; (ii) increase
      reactive oxygen species (ROS) production to 84 +/- 21% and change the
      physiological status of microbial cells after 96 h of treatment; (iii) seriously
      affect a 72-h old established biofilm, increasing the level of oxidative stress
      to 86 +/- 21%. Moreover, the results indicate that oxygen renders the biofilm
      more adequate to counteract AgNP effects. Comet assays on Caco-2 cells
      demonstrated a protective role of biofilm against the genotoxic effect of 1
      MUg/mL AgNPs on intestinal epithelial cells.

PMID- 29379490
TI  - Polyelectrolyte Multicomponent Colloidosomes Loaded with Nisin Z for Enhanced
      Antimicrobial Activity against Foodborne Resistant Pathogens.
AB  - Food grade micro- or nano-carrier systems (NCS) are being developed to improve
      the controlled release of antimicrobial agents. To augment the stability of
      liposomal NCS and to overcome the limitations associated with the use of free
      bacteriocin (nisin) in the food system, multi-component colloidosomes (MCCS) were
      developed by electrostatic interactions between anionic alginate and cationic
      chitosan (multilayer) around phospholipids based liposomes (core). Zeta-sizer
      results revealed the average diameter of 145 +/- 2 nm, 596 +/- 3 nm, and 643 +/-
      5 nm for nano-liposome (NL), chitosomes (chitosan coated NL) and MCCS,
      respectively. Zeta potential values of NCS varied from -4.37 +/- 0.16 mV to 33.3
      +/- 6 mV, thus both chitosomes (CS) and MCCS were positively charged.
      Microstructure analysis by scanning electron microscope (SEM) revealed relatively
      higher size of MCCS with smooth and round morphology. TGA and DSC based
      experiments revealed that MCCS were thermally more stable than uncoated
      liposomes. Encapsulation efficiency of nisin in MCCS was observed to be 82.9 +/-
      4.1%, which was significantly higher than NL (56.5 +/- 2.5%). FTIR analyses
      confirmed the cross-linking between sodium alginate and chitosan layer. Both
      qualitative (growth kinetics) and quantitative (colony forming unit)
      antimicrobial assays revealed that nisin loaded MCCS have superior potential to
      control resistant foodborne pathogens including Staphylococcus aureus, Listeria
      monocytogenes, and Enterococcus faecalis, (5.8, 5.4, and 6.1 Log CFUmL-1
      reduction, respectively) as compared to free nisin, loaded NL or CS. Controlled
      release kinetics data fitted with Korsmeyer-Peppas model suggested that nisin
      release from MCCS followed Fickian diffusion. Cytotoxic studies on human blood
      cells and HepG2 cell lines revealed hemocompatibility and non-toxicity of MCCS.
      Thus, due to enhanced controlled release, stability and biocompatibility; these
      multi-component colloidosomes can be useful for incorporating antimicrobial
      agents into functional foods, beverages and pharmaceutical products to combat
      pathogenic and spoilage bacteria.

PMID- 29379491
TI  - Lipids, pH, and Their Interaction Affect the Inhibitory Effects of Carvacrol
      against Salmonella Typhimurium PT4 and Escherichia coli O157:H7.
AB  - Although carvacrol (CAR) is considered an alternative antimicrobial for use in
      food, few is known about the influence of food-related parameters on its
      inhibitory effects against pathogens. This study assessed the influence of
      different amounts of proteins, using beef extract (BE) as a protein-rich source,
      lipids (LIP), using sunflower oil as a LIP-rich source, and pH values or their
      interaction on the inhibitory effects of CAR against Salmonella Typhimurium PT4
      (ST) and Escherichia coli O157:H7 (EC). The specific maximum growth rate (MUmax)
      and lag phase duration (lambda) of the test pathogens when exposed to CAR in
      media with different amounts of BE (4, 6, and 8 g/100 mL), LIP (3.75, 5, and 6.25
      mL/100 mL), and pH values (5, 5.5, and 6) were determined. The viable counts of
      the tested pathogens in media that promoted the highest and lowest MUmax in the
      presence of CAR were monitored during 24 h. The lowest MUmax of ST and EC exposed
      to 2.4 MUL/mL (-1.29 and -0.82 log CFU/mL/h, respectively) or 4.8 MUL/mL CAR (
      1.44 and -2.17 log CFU/mL/h, respectively) were observed in media with the
      highest LIP amount (6.25 mL/100 mL) and pH value (pH 6). For both SE and EC, the
      longest lambda (> 2 h) was verified in media where these pathogens showed the
      lowest MUmax. These data indicate that the concomitant increase in LIP amounts
      and pH values affected positively the CAR inhibitory effects against the target
      pathogens. CAR (2.4 or 4.8 MUL/mL) failed to inhibit the increase in ST and EC
      counts in media where the highest MUmax values were previously observed. On the
      contrary, CAR inhibited the increase of ST counts (final counts 5 log CFU/mL) and
      decreased the EC counts (final counts 3.5 log CFU/mL) in media where the lowest
      MUmax values were observed. These results show that the inhibitory effects of CAR
      on ST and EC in food matrices could be affected as a function of the interaction
      of LIP amounts and pH values.

PMID- 29379492
TI  - African Lineage Brucella melitensis Isolates from Omani Livestock.
AB  - Brucellosis is a common livestock disease in the Middle East and North Africa,
      but remains poorly described in the region both genetically and
      epidemiologically. Traditionally found in goats and sheep, Brucella melitensis is
      increasingly recognized as infecting camels. Most studies of brucellosis in
      camels to date have focused on serological surveys, providing only limited
      understanding of the molecular epidemiology of circulating strains. We genotyped
      B. melitensis isolates from Omani camels using whole genome SNP assays and VNTRs
      to provide context for regional brucellosis cases. We identified a lineage of B.
      melitensis circulating in camels as well as in goats, sheep, and cattle in Oman.
      This lineage is genetically distinct from most genotypes from the Arabian
      Peninsula and from isolates from much of the rest of the Middle East. We then
      developed diagnostic assays that rapidly identify strains from this lineage. In
      analyses of genotypes from throughout the region, Omani isolates were genetically
      most closely related to strains from brucellosis cases in humans and livestock in
      North Africa. Our findings suggest an African origin for B. melitensis in Oman
      that has likely occurred through the trade of infected livestock. Moreover,
      African lineages of B. melitensis appear to be undersampled and consequently are
      underrepresented in genetic databases for Brucella. As we begin to more fully
      understand global genomic diversity of B. melitensis, finding and characterizing
      these unique but widespread lineages is essential. We predict that increased
      sampling of humans and livestock in Africa will reveal little known diversity in
      this important zoonotic pathogen.

PMID- 29379493
TI  - Progress and Challenges in the Design and Clinical Development of Antibodies for
      Cancer Therapy.
AB  - The remarkable progress in engineering and clinical development of therapeutic
      antibodies in the last 40 years, after the seminal work by Kohler and Milstein,
      has led to the approval by the United States Food and Drug Administration (FDA)
      of 21 antibodies for cancer immunotherapy. We review here these approved
      antibodies, with emphasis on the methods used for their discovery, engineering,
      and optimization for therapeutic settings. These methods include antibody
      engineering via chimerization and humanization of non-human antibodies, as well
      as selection and further optimization of fully human antibodies isolated from
      human antibody phage-displayed libraries and immunization of transgenic mice
      capable of generating human antibodies. These technology platforms have
      progressively led to the development of therapeutic antibodies with higher human
      content and, thus, less immunogenicity. We also discuss the genetic engineering
      approaches that have allowed isotype switching and Fc modifications to modulate
      effector functions and bioavailability (half-life), which together with the
      technologies for engineering the Fv fragment, have been pivotal in generating
      more efficacious and better tolerated therapeutic antibodies to treat cancer.

PMID- 29379494
TI  - The CXCR4-STAT3-IL-10 Pathway Controls the Immunoregulatory Function of Chronic
      Lymphocytic Leukemia and Is Modulated by Lenalidomide.
AB  - Chronic lymphocytic leukemia (CLL) cells possess regulatory functions comparable
      to those of normal B10 cells, a regulatory B cell subset that suppresses effector
      T-cell function through STAT3-mediated IL-10 production. However, the mechanisms
      governing IL-10 production by CLL cells are not fully understood. Here, we show
      that the CXC chemokine ligand 12 (CXCL12)-CXCR4-STAT3 axis regulates IL-10
      production by CLL cells and their ability to suppress T-cell effector function
      through an IL-10 mediated mechanism. Knockdown of STAT3 significantly impaired
      the ability of CLL cells to produce IL-10. Furthermore, experiments to assess the
      role of lenalidomide, an immunomodulatory agent with direct antitumor effect as
      well as pleiotropic activity on the immune system, showed that this agent
      prevents a CXCL12-induced increase in p-S727-STAT3 and the IL-10 response by CLL
      cells. Lenalidomide also suppressed IL-10-induced Y705-STAT3 phosphorylation in
      healthy T cells, thus reversing CLL-induced T-cell dysfunction. We conclude that
      the capacity of CLL cells to produce IL-10 is mediated by the CXCL12-CXCR4-STAT3
      pathway and likely contributes to immunodeficiency in patients. Lenalidomide
      appears to be able to reverse CLL-induced immunosuppression through including
      abrogation of the CXCL12-CXCR4-S727-STAT3-mediated IL-10 response by CLL cells
      and prevention of IL-10-induced phosphorylation of Y705-STAT3 in T cells.

PMID- 29379495
TI  - AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and
      Antiviral Immunity.
AB  - Dendritic cells (DCs) must integrate a broad array of environmental cues to exact
      control over downstream immune responses including TH polarization. The
      multienzyme aminoacyl-tRNA synthetase complex component AIMp1/p43 responds to
      cellular stress and exerts pro-inflammatory functions; however, a role for DC
      expressed AIMp1 in TH polarization has not previously been shown. Here, we
      demonstrate that the absence of AIMp1 in bone marrow-derived DC (BMDC)
      significantly impairs cytokine and costimulatory molecule expression, p38 MAPK
      signaling, and TH1 polarization of cocultured T-cells while significantly
      dysregulating immune-related gene expression. These deficits resulted in
      significantly compromised BMDC vaccine-mediated protection against melanoma.
      AIMp1 within the host was also critical for innate and adaptive antiviral
      immunity against influenza virus infection in vivo. Cancer patients with AIMp1
      expression levels in the highest tertiles exhibited a 70% survival advantage at
      15-year postdiagnosis as determined by bioinformatics analysis of nearly 9,000
      primary human tumor samples in The Cancer Genome Atlas database. These data
      establish the importance of AIMp1 for the effective governance of antitumor and
      antiviral immune responses.

PMID- 29379497
TI  - Effects of Anti-IL-17 on Inflammation, Remodeling, and Oxidative Stress in an
      Experimental Model of Asthma Exacerbated by LPS.
AB  - Inflammation plays a central role in the development of asthma, which is
      considered an allergic disease with a classic Th2 inflammatory profile. However,
      cytokine IL-17 has been examined to better understand the pathophysiology of this
      disease. Severe asthmatic patients experience frequent exacerbations, leading to
      infection, and subsequently show altered levels of inflammation that are unlikely
      to be due to the Th2 immune response alone. This study estimates the effects of
      anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model
      exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin
      and repeatedly exposed to inhalation with ovalbumin, followed by treatment with
      or without anti-IL-17. Twenty-four hours prior to the end of the 29-day
      experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA
      LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid,
      performed a lung tissue morphometric analysis, and measured IL-6 gene expression.
      OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary
      inflammation, edema, oxidative stress, and extracellular matrix remodeling
      compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17
      treatment also decreased the numbers of dendritic cells, FOXP3, NF-kappaB, and
      Rho kinase 1- and 2-positive cells compared to the non-treated OVA and OVA-LPS
      groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is
      a promising therapeutic avenue, even in exacerbated asthmatic patients, and
      significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine
      expression, extracellular matrix remodeling, and oxidative stress in a murine
      experimental asthma model exacerbated by LPS.

PMID- 29379496
TI  - Type I Interferon Responses by HIV-1 Infection: Association with Disease
      Progression and Control.
AB  - Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired
      immunodeficiency syndrome and its infection leads to the onset of several
      disorders such as the depletion of peripheral CD4+ T cells and immune activation.
      HIV-1 is recognized by innate immune sensors that then trigger the production of
      type I interferons (IFN-Is). IFN-Is are well-known cytokines eliciting broad anti
      viral effects by inducing the expression of anti-viral genes called interferon
      stimulated genes (ISGs). Extensive in vitro studies using cell culture systems
      have elucidated that certain ISGs such as APOBEC3G, tetherin, SAM domain and HD
      domain-containing protein 1, MX dynamin-like GTPase 2, guanylate-binding protein
      5, and schlafen 11 exert robust anti-HIV-1 activity, suggesting that IFN-I
      responses triggered by HIV-1 infection are detrimental for viral replication and
      spread. However, recent studies using animal models have demonstrated that at
      both the acute and chronic phase of infection, the role of IFN-Is produced by HIV
      or SIV infection in viral replication, spread, and pathogenesis, may not be that
      straightforward. In this review, we describe the pluses and minuses of HIV-1
      infection stimulated IFN-I responses on viral replication and pathogenesis, and
      further discuss the possibility for therapeutic approaches.

PMID- 29379498
TI  - Minimum Information about T Regulatory Cells: A Step toward Reproducibility and
      Standardization.
AB  - Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of
      efficacious treatment for the variety of autoimmune and allergic diseases as well
      as posttransplant complications. Nevertheless, current manufacturing of Tregs as
      a cellular medicinal product varies between different laboratories, which in turn
      hampers precise comparisons of the results between the studies performed. While
      the number of clinical trials testing Tregs is already substantial, it seems to
      be crucial to provide some standardized characteristics of Treg products in order
      to minimize the problem. We have previously developed reporting guidelines called
      minimum information about tolerogenic antigen-presenting cells, which allows the
      comparison between different preparations of tolerance-inducing antigen
      presenting cells. Having this experience, here we describe another minimum
      information about Tregs (MITREG). It is important to note that MITREG does not
      dictate how investigators should generate or characterize Tregs, but it does
      require investigators to report their Treg data in a consistent and transparent
      manner. We hope this will, therefore, be a useful tool facilitating standardized
      reporting on the manufacturing of Tregs, either for research purposes or for
      clinical application. This way MITREG might also be an important step toward more
      standardized and reproducible testing of the Tregs preparations in clinical
      applications.

PMID- 29379500
TI  - Intravital Microscopic Evaluation of the Effects of a CXCR2 Antagonist in a Model
      of Liver Ischemia Reperfusion Injury in Mice.
AB  - Background: Ischemia-reperfusion (IR) is a major contributor to graft rejection
      after liver transplantation. During IR injury, an intense inflammatory process
      occurs in the liver. Neutrophils are considered central players in the events
      that lead to liver injury. CXC chemokines mediate hepatic inflammation following
      reperfusion. However, few studies have demonstrated in real-time the behavior of
      recruited neutrophils. We used confocal intravital microscopy (IVM) to image
      neutrophil migration in the liver and to analyze in real-time parameters of
      neutrophil recruitment in the inflamed tissue in animals treated or not with
      reparixin, an allosteric antagonist of CXCR1/2 receptors. Materials and methods:
      WT and LysM-eGFP mice treated with reparixin or saline were subjected to 60 min
      of ischemia followed by different times of reperfusion. Mice received Sytox
      orange intravenously to show necrotic DNA in IVM. The effect of reparixin on
      parameters of local and systemic reperfusion-induced injury was also
      investigated. Results: IR induced liver injury and inflammation, as evidenced by
      high levels of alanine aminotransferase and myeloperoxidase activity, chemokine
      and cytokine production, and histological outcome. Treatment with reparixin
      significantly decreased neutrophil influx. Moreover, reparixin effectively
      suppressed the increase in serum concentrations of TNF-alpha, IL-6, and CCL3, and
      the reperfusion-associated tissue damage. The number of neutrophils in the liver
      increased between 6 and 24 h of reperfusion, whereas the distance traveled,
      velocity, neutrophil size and shape, and cluster formation reached a maximum 6 h
      after reperfusion and then decreased gradually. In vivo imaging revealed that
      reparixin significantly decreased neutrophil infiltration and movement and
      displacement of recruited cells. Moreover, neutrophils had a smaller size and
      less elongated shape in treated mice. Conclusion: Imaging of the liver by
      confocal IVM was successfully implemented to describe neutrophil behavior in vivo
      during liver injury by IR. Treatment with reparixin decreased not only the
      recruitment of neutrophils in tissues but also their activation state and
      capacity to migrate within the liver. CXCR1/2 antagonists may be a promising
      therapy for patients undergoing liver transplantation.

PMID- 29379499
TI  - S100 Proteins As an Important Regulator of Macrophage Inflammation.
AB  - The S100 proteins, a family of calcium-binding cytosolic proteins, have a broad
      range of intracellular and extracellular functions through regulating calcium
      balance, cell apoptosis, migration, proliferation, differentiation, energy
      metabolism, and inflammation. The intracellular functions of S100 proteins
      involve interaction with intracellular receptors, membrane protein
      recruitment/transportation, transcriptional regulation and integrating with
      enzymes or nucleic acids, and DNA repair. The S100 proteins could also be
      released from the cytoplasm, induced by tissue/cell damage and cellular stress.
      The extracellular S100 proteins, serving as a danger signal, are crucial in
      regulating immune homeostasis, post-traumatic injury, and inflammation.
      Extracellular S100 proteins are also considered biomarkers for some specific
      diseases. In this review, we will discuss the multi-functional roles of S100
      proteins, especially their potential roles associated with cell migration,
      differentiation, tissue repair, and inflammation.

PMID- 29379501
TI  - Expression of Siglec-E Alters the Proteome of Lipopolysaccharide (LPS)-Activated
      Macrophages but Does Not Affect LPS-Driven Cytokine Production or Toll-Like
      Receptor 4 Endocytosis.
AB  - Siglec-E is a murine CD33-related siglec that functions as an inhibitory receptor
      and is expressed mainly on neutrophils and macrophage populations. Recent studies
      have suggested that siglec-E is an important negative regulator of
      lipopolysaccharide (LPS)-toll-like receptor 4 (TLR4) signaling and one report (1)
      claimed that siglec-E is required for TLR4 endocytosis following uptake of
      Escherichia coli by macrophages and dendritic cells (DCs). Our attempts to
      reproduce these observations using cells from wild-type (WT) and siglec-E
      deficient mice were unsuccessful. We used a variety of assays to determine if
      siglec-E expressed by different macrophage populations can regulate TLR4
      signaling in response to LPS, but found no consistent differences in cytokine
      secretion in vitro and in vivo, comparing three different strains of siglec-E
      deficient mice with matched WT controls. No evidence was found that the siglec-E
      deficiency was compensated by expression of siglecs-F and -G, the other murine
      inhibitory CD33-related siglecs. Quantitative proteomics was used as an unbiased
      approach and provided additional evidence that siglec-E does not suppress
      inflammatory TLR4 signaling. Interestingly, proteomics revealed a siglec-E
      dependent alteration in macrophage protein composition that could be relevant to
      functional responses in host defense. In support of this, siglec-E-deficient mice
      exhibited enhanced growth of Salmonella enterica serovar Typhimurium in the liver
      following intravenous infection, but macrophages lacking siglec-E did not show
      altered uptake or killing of bacteria in vitro. Using various cell types
      including bone marrow-derived DCs (BMDCs), splenic DCs, and macrophages from WT
      and siglec-E-deficient mice, we showed that siglec-E is not required for TLR4
      endocytosis following E. coli uptake or LPS challenge. We failed to see
      expression of siglec-E by BMDC even after LPS-induced maturation, but confirmed
      previous studies that splenic DCs express low levels of siglec-E. Taken together,
      our findings do not support a major role of siglec-E in regulation of TLR4
      signaling functions or TLR4 endocytosis in macrophages or DCs. Instead, they
      reveal that induction of siglec-E by LPS can modulate the phenotype of
      macrophages, the functional significance of which is currently unclear.

PMID- 29379502
TI  - Redefining the Role of Langerhans Cells As Immune Regulators within the Skin.
AB  - Langerhans cells (LC) are a unique population of tissue-resident macrophages that
      form a network of cells across the epidermis of the skin, but which have the
      ability to migrate from the epidermis to draining lymph nodes (LN). Their
      location at the skin barrier suggests a key role as immune sentinels. However,
      despite decades of research, the role of LC in skin immunity is unclear; ablation
      of LC results in neither fatal susceptibility to skin infection nor overt
      autoimmunity due to lack of immune regulation. Our understanding of immune
      processes has traditionally been centered on secondary lymphoid organs as sites
      of lymphocyte priming and differentiation, which is exemplified by LC, initially
      defined as a paradigm for tissue dendritic cells that migrate to draining LN on
      maturation. But, more recently, an awareness of the importance of the tissue
      environment in shaping effector immunity has emerged. In this mini-review, we
      discuss whether our lack of understanding of LC function stems from our lymph
      node-centric view of these cells, and question whether a focus on LC as immune
      regulators in situ in the skin may reveal clearer answers about their function in
      cutaneous immunology.

PMID- 29379503
TI  - Infection of Human Macrophages by Leishmania infantum Is Influenced by Ecto
      Nucleotidases.
AB  - Ecto-nucleotidase activity is involved in the infection process of Leishmania and
      various other parasites that enables modulation of host immune responses to
      promote disease progression. One of the enzymes responsible for this activity is
      the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase). The enzyme
      hydrolyzes nucleotides tri- and/or di-phosphate into monophosphate products,
      which are subsequently hydrolyzed into adenosine. These nucleotides can serve as
      purinergic signaling molecules involved in diverse cellular processes that govern
      immune responses. Given the importance of the extracellular metabolism of these
      nucleotides during intracellular pathogen infections, this study evaluates the
      role of ecto-nucleotidase activity during Leishmania infantum (L. infantum)
      infection in human macrophages. E-NTPDase protein expression and activity was
      evaluated in L. infantum during purine starvation, adenosine-enriched medium, or
      in the presence of an inhibitor of ecto-nucleotidases. Results show that E
      NTPDase is expressed in L. infantum parasites, including on the cell membrane.
      Furthermore, functional activity of the enzyme was modulated according to the
      availability of adenosine in the medium. Purine starvation increased the
      hydrolytic capacity of nucleotides leading to higher infectivity, while growth in
      adenosine-enriched medium led to lower infectivity. Moreover, inhibiting E
      NTPDase function decreased L. infantum infection in macrophages, suggesting the
      enzyme may serve as a ligand. Taken together, the ability of L. infantum to
      hydrolyze nucleotides is directly associated with increased infectivity in
      macrophages.

PMID- 29379505
TI  - High-Salt Diet Induces IL-17-Dependent Gut Inflammation and Exacerbates Colitis
      in Mice.
AB  - Excess intake of sodium is often associated with high risk for cardiovascular
      disease. More recently, some studies on the effects of high-salt diets (HSDs)
      have also demonstrated that they are able to activate Th17 cells and increase
      severity of autoimmune diseases. The purpose of the present study was to evaluate
      the effects of a diet supplemented with NaCl in the colonic mucosa at steady
      state and during inflammation. We showed that consumption of HSD by mice
      triggered a gut inflammatory reaction associated with IL-23 production,
      recruitment of neutrophils, and increased frequency of the IL-17-producing type 3
      innate lymphoid cells (ILC3) in the colon. Moreover, gut inflammation was not
      observed in IL-17-/- mice but it was present, although at lower grade, in RAG-/-
      mice suggesting that the inflammatory effects of HSD was dependent on IL-17 but
      only partially on Th17 cells. Expression of SGK1, a kinase involved in sodium
      homeostasis, increased 90 min after ingestion of 50% NaCl solution and decreased
      3 weeks after HSD consumption. Colitis induced by oral administration of either
      dextran sodium sulfate or 2,4,6-trinitrobenzenesulfonic acid was exacerbated by
      HSD consumption and this effect was associated with increased frequencies of
      RORgammat+ CD4+ T cells and neutrophils in the colon. Therefore, our results
      demonstrated that consumption of HSD per se triggered a histologically detectable
      inflammation in the colon and also exacerbated chemically induced models of
      colitis in mice by a mechanism dependent on IL-17 production most likely by both
      ILC3 and Th17 cells.

PMID- 29379504
TI  - Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite
      and Its Link to Pathological Conditions.
AB  - Tryptophan metabolites are known to participate in the regulation of many cells
      of the immune system and are involved in various immune-mediated diseases and
      disorders. Kynurenic acid (KYNA) is a product of one branch of the kynurenine
      pathway of tryptophan metabolism. The influence of KYNA on important
      neurophysiological and neuropathological processes has been comprehensively
      documented. In recent years, the link of KYNA to the immune system, inflammation,
      and cancer has become more apparent. Given this connection, the anti-inflammatory
      and immunosuppressive functions of KYNA are of particular interest. These
      characteristics might allow KYNA to act as a "double-edged sword." The metabolite
      contributes to both the resolution of inflammation and the establishment of an
      immunosuppressive environment, which, for instance, allows for tumor immune
      escape. Our review provides a comprehensive update of the significant biological
      functions of KYNA and focuses on its immunomodulatory properties by signaling via
      G-protein-coupled receptor 35 (GPR35)- and aryl hydrocarbon receptor-mediated
      pathways. Furthermore, we discuss the role of KYNA-GPR35 interaction and
      microbiota associated KYNA metabolism for gut homeostasis.

PMID- 29379507
TI  - High Antigen Dose Is Detrimental to Post-Exposure Vaccine Protection against
      Tuberculosis.
AB  - Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB),
      causes 1.8M deaths annually. The current vaccine, BCG, has failed to eradicate TB
      leaving 25% of the world's population with latent Mtb infection (LTBI), and 5-10%
      of these people will reactivate and develop active TB. An efficient therapeutic
      vaccine targeting LTBI could have an enormous impact on global TB incidence, and
      could be an important aid in fighting multidrug resistance, which is increasing
      globally. Here we show in a mouse model using the H56 (Ag85B-ESAT-6-Rv2660) TB
      vaccine candidate that post-exposure, but not preventive, vaccine protection
      requires low vaccine antigen doses for optimal protection. Loss of protection
      from high dose post-exposure vaccination was not associated with a loss of
      overall vaccine response magnitude, but rather with greater differentiation and
      lower functional avidity of vaccine-specific CD4 T cells. High vaccine antigen
      dose also led to a decreased ability of vaccine-specific CD4 T cells to home into
      the Mtb-infected lung parenchyma, a recently discovered important feature of T
      cell protection in mice. These results underscore the importance of T cell
      quality rather than magnitude in TB-vaccine protection, and the significant role
      that antigen dosing plays in vaccine-mediated protection.

PMID- 29379508
TI  - Classic Ulcerative Pyoderma Gangrenosum Is a T Cell-Mediated Disease Targeting
      Follicular Adnexal Structures: A Hypothesis Based on Molecular and
      Clinicopathologic Studies.
AB  - Background: Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease
      that is one of the most common associated diseases seen in patients with
      inflammatory bowel disease and rheumatoid arthritis. Although PG is classified as
      a neutrophilic dermatosis, its pathophysiology is poorly understood. Objective:
      Use data obtained from patient-reported histories, immunohistochemistry, and gene
      expression analysis to formulate a hypothesis on PG pathophysiology. Methods: Ten
      PG patients participated and answered questions about new ulcer formation. Skin
      biopsies of healed prior ulcers and adjacent normal skin were obtained from four
      patients for immunohistochemistry. Scars from healthy patients and patients with
      discoid lupus were used as additional controls. New onset PG papules were
      analyzed using immunohistochemistry and gene expression analysis via quantitative
      real-time PCR. Results: All PG patients reported that healed sites of previous
      ulceration are refractory to re-ulceration. Simultaneous biopsies of healed and
      uninvolved skin triggered ulceration only in the latter. On immunohistochemistry,
      healed PG scars showed complete loss of pilosebaceous units, which were present
      in normal skin, and to a lesser extent in control scars, and discoid scars. Early
      PG papules showed perivascular and peripilosebaceous T cell infiltrates, rather
      than neutrophils. These early inflammatory events were dominated by increased
      gene expression of CXCL9, CXCL10, CXCL11, IL-8, IL-17, IFNG, and IL-36G and
      transcription factors consistent with Th1 phenotype. Limitations: Small sample
      size was the main limitation. Conclusion: We put forth the hypothesis that PG is
      a T cell response resulting in the destruction of pilosebaceous units.

PMID- 29379509
TI  - NETQUANT: Automated Quantification of Neutrophil Extracellular Traps.
AB  - Neutrophil extracellular traps (NETs) that are extensive webs of DNA covered with
      antimicrobial proteins into the extracellular environment during infection or
      inflammation as a part of their defense arsenal. Image acquisition of
      fluorescently labeled NETs and subsequent image-based quantification is
      frequently used to analyze NET formation (NETosis) in response to various
      stimuli. However, there are important limitations in the present methods for
      quantification. Manual methods tend to be error-prone, tedious, and often quite
      subjective, whereas the software-rooted options are either semi-automatic or
      difficult to operate. Here, we present an automated and uncomplicated approach
      for quantifying NETs from fluorescence images, built as a freely available app
      for MATLAB(r). It is based on detection of a set of clearly defined parameters,
      all related to the biological manifestation of NETs and allowing for single-cell
      resolution quantification and analysis.

PMID- 29379506
TI  - Overview of the Mechanisms that May Contribute to the Non-Redundant Activities of
      Interferon-Inducible CXC Chemokine Receptor 3 Ligands.
AB  - The inflammatory chemokines CXCL9, CXCL10, and CXCL11 are predominantly induced
      by interferon (IFN)-gamma and share an exclusive chemokine receptor named CXC
      chemokine receptor 3 (CXCR3). With a prototype function of directing temporal and
      spatial migration of activated T cells and natural killer cells, and inhibitory
      effects on angiogenesis, these CXCR3 ligands have been implicated in infection,
      acute inflammation, autoinflammation and autoimmunity, as well as in cancer.
      Intense former research efforts led to recent and ongoing clinical trials using
      CXCR3 and CXCR3 ligand targeting molecules. Scientific evidence has claimed
      mutual redundancy, ligand dominance, collaboration or even antagonism, depending
      on the (patho)physiological context. Most research on their in vivo activity,
      however, illustrates that CXCL9, CXCL10, and CXCL11 each contribute to the
      activation and trafficking of CXCR3 expressing cells in a non-redundant manner.
      When looking into detail, one can unravel a multistep machinery behind final
      CXCR3 ligand functions. Not only can specific cell types secrete individual CXCR3
      interacting chemokines in response to certain stimuli, but also the receptor and
      glycosaminoglycan interactions, major associated intracellular pathways and
      susceptibility to processing by particular enzymes, among others, seem ligand
      specific. Here, we overview major aspects of the molecular properties and
      regulatory mechanisms of IFN-induced CXCR3 ligands, and propose that their in
      vivo non-redundancy is a reflection of the unprecedented degree of versatility
      that seems inherent to the IFN-related CXCR3 chemokine system.

PMID- 29379510
TI  - Large-Scale Identification and Characterization of Heterodera avenae Putative
      Effectors Suppressing or Inducing Cell Death in Nicotiana benthamiana.
AB  - Heterodera avenae is one of the most important plant pathogens and causes vast
      losses in cereal crops. As a sedentary endoparasitic nematode, H. avenae secretes
      effectors that modify plant defenses and promote its biotrophic infection of its
      hosts. However, the number of effectors involved in the interaction between H.
      avenae and host defenses remains unclear. Here, we report the identification of
      putative effectors in H. avenae that regulate plant defenses on a large scale.
      Our results showed that 78 of the 95 putative effectors suppressed programmed
      cell death (PCD) triggered by BAX and that 7 of the putative effectors themselves
      caused cell death in Nicotiana benthamiana. Among the cell-death-inducing
      effectors, three were found to be dependent on their specific domains to trigger
      cell death and to be expressed in esophageal gland cells by in situ
      hybridization. Ten candidate effectors that suppressed BAX-triggered PCD also
      suppressed PCD triggered by the elicitor PsojNIP and at least one R
      protein/cognate effector pair, suggesting that they are active in suppressing
      both pattern-triggered immunity (PTI) and effector-triggered immunity (ETI).
      Notably, with the exception of isotig16060, these putative effectors could also
      suppress PCD triggered by cell-death-inducing effectors from H. avenae,
      indicating that those effectors may cooperate to promote nematode parasitism.
      Collectively, our results indicate that the majority of the tested effectors of
      H. avenae may play important roles in suppressing cell death induced by different
      elicitors in N. benthamiana.

PMID- 29379511
TI  - Considerations for Achieving Cross-Platform Point Cloud Data Fusion across
      Different Dryland Ecosystem Structural States.
AB  - Remotely sensing recent growth, herbivory, or disturbance of herbaceous and woody
      vegetation in dryland ecosystems requires high spatial resolution and multi
      temporal depth. Three dimensional (3D) remote sensing technologies like lidar,
      and techniques like structure from motion (SfM) photogrammetry, each have
      strengths and weaknesses at detecting vegetation volume and extent, given the
      instrument's ground sample distance and ease of acquisition. Yet, a combination
      of platforms and techniques might provide solutions that overcome the weakness of
      a single platform. To explore the potential for combining platforms, we compared
      detection bias amongst two 3D remote sensing techniques (lidar and SfM) using
      three different platforms [ground-based, small unmanned aerial systems (sUAS),
      and manned aircraft]. We found aerial lidar to be more accurate for
      characterizing the bare earth (ground) in dense herbaceous vegetation than either
      terrestrial lidar or aerial SfM photogrammetry. Conversely, the manned aerial
      lidar did not detect grass and fine woody vegetation while the terrestrial lidar
      and high resolution near-distance (ground and sUAS) SfM photogrammetry detected
      these and were accurate. UAS SfM photogrammetry at lower spatial resolution under
      estimated maximum heights in grass and shrubs. UAS and handheld SfM
      photogrammetry in near-distance high resolution collections had similar accuracy
      to terrestrial lidar for vegetation, but difficulty at measuring bare earth
      elevation beneath dense herbaceous cover. Combining point cloud data and
      derivatives (i.e., meshes and rasters) from two or more platforms allowed for
      more accurate measurement of herbaceous and woody vegetation (height and canopy
      cover) than any single technique alone. Availability and costs of manned aircraft
      lidar collection preclude high frequency repeatability but this is less limiting
      for terrestrial lidar, sUAS and handheld SfM. The post-processing of SfM
      photogrammetry data became the limiting factor at larger spatial scale and
      temporal repetition. Despite the utility of sUAS and handheld SfM for monitoring
      vegetation phenology and structure, their spatial extents are small relative to
      manned aircraft.

PMID- 29379512
TI  - Genomic, Biochemical, and Modeling Analyses of Asparagine Synthetases from Wheat.
AB  - Asparagine synthetase activity in cereals has become an important issue with the
      discovery that free asparagine concentration determines the potential for
      formation of acrylamide, a probably carcinogenic processing contaminant, in baked
      cereal products. Asparagine synthetase catalyses the ATP-dependent transfer of
      the amino group of glutamine to a molecule of aspartate to generate glutamate and
      asparagine. Here, asparagine synthetase-encoding polymerase chain reaction (PCR)
      products were amplified from wheat (Triticum aestivum) cv. Spark cDNA. The
      encoded proteins were assigned the names TaASN1, TaASN2, and TaASN3 on the basis
      of comparisons with other wheat and cereal asparagine synthetases. Although very
      similar to each other they differed slightly in size, with molecular masses of
      65.49, 65.06, and 66.24 kDa, respectively. Chromosomal positions and scaffold
      references were established for TaASN1, TaASN2, and TaASN3, and a fourth, more
      recently identified gene, TaASN4. TaASN1, TaASN2, and TaASN4 were all found to be
      single copy genes, located on chromosomes 5, 3, and 4, respectively, of each
      genome (A, B, and D), although variety Chinese Spring lacked a TaASN2 gene in the
      B genome. Two copies of TaASN3 were found on chromosome 1 of each genome, and
      these were given the names TaASN3.1 and TaASN3.2. The TaASN1, TaASN2, and TaASN3
      PCR products were heterologously expressed in Escherichia coli (TaASN4 was not
      investigated in this part of the study). Western blot analysis identified two
      monoclonal antibodies that recognized the three proteins, but did not distinguish
      between them, despite being raised to epitopes SKKPRMIEVAAP and GGSNKPGVMNTV in
      the variable C-terminal regions of the proteins. The heterologously expressed
      TaASN1 and TaASN2 proteins were found to be active asparagine synthetases,
      producing asparagine and glutamate from glutamine and aspartate. The asparagine
      synthetase reaction was modeled using SNOOPY(r) software and information from the
      BRENDA database to generate differential equations to describe the reaction
      stages, based on mass action kinetics. Experimental data from the reactions
      catalyzed by TaASN1 and TaASN2 were entered into the model using Copasi, enabling
      values to be determined for kinetic parameters. Both the reaction data and the
      modeling showed that the enzymes continued to produce glutamate even when the
      synthesis of asparagine had ceased due to a lack of aspartate.

PMID- 29379513
TI  - Microalgae in Microwell Arrays Exhibit Differences with Those in Flasks: Evidence
      from Growth Rate, Cellular Carotenoid, and Oxygen Production.
AB  - Microalgae are cultivated in macro-scale reactors traditionally and the relevant
      knowledge is based on bulk analysis. Whether the knowledge and laws are true for
      cells under micro-cultivation is still unknown. To better understand microalgal
      physiology, micro-cultivation of microalgae, and unicellular tracking and
      analysis of its response in vivo is necessary. In the study, cellular responses
      of Chlorella vulgaris to micro-cultivation is studied, with cells in flasks as a
      control. Five different microwell depths ranging from 10 to 200 MUm with a fixed
      diameter of 100 MUm, and four diameter levels from 30 to 200 MUm with a fixed
      depth 60 MUm were investigated. Unicellular dynamics showed that cell number
      differences among various types of microwells with different initial cell numbers
      decreased as cultivation processed. Besides, the specific growth rate of C.
      vulgaris on microwell arrays was much higher than that in flasks and so cells on
      microwell arrsys can be much sensitive to pollutants. Thus, the interesting
      characteristics may be used in cell sensor applications to enhance sensitivity.
      The specific growth rate of C. vulgaris on microwell arrays decreased gradually
      as the microwell diameter increased from 30 to 200 MUm while presented a unimodal
      trend as depth decreased from 200 to 10 MUm. Furthermore, we used Raman
      Spectroscopy and Non-invasive Micro-test Technique to analyze cellular responses
      in microwells for the first time to track the changes in vivo. Results indicated
      that unicellular carotenoid content increased as microwells became larger and
      shallower. The flow rate of oxygen rose gradually as the depth increased from 10
      to 100 MUm, but then decreased rapidly as the depth deepened to 200 MUm. In fact,
      it is a combined result of cell physiology and density. In summary, cells in
      microwells with the diameter/depth ratio ~1 owned the highest specific growth
      rates and oxygen flow rates. Simulations also suggested that better mass transfer
      occurred in microwells with higher diameter-to-depth ratios.

PMID- 29379514
TI  - Hydrological Conditions Affect the Interspecific Interaction between Two Emergent
      Wetland Species.
AB  - Hydrological conditions determine the distribution of plant species in wetlands,
      where conditions such as water depth and hydrological fluctuations are expected
      to affect the interspecific interactions among emergent wetland species. To test
      such effects, we conducted a greenhouse experiment with three treatment
      categories, interspecific interaction (mixed culture or monoculture), water depth
      (10 or 30 cm depth), and hydrological fluctuation (static or fluctuating water
      level), and two common emergent wetland plant species, Scirpus planiculumis Fr.
      (Cyperaceae) and Phragmites australis var. baiyangdiansis (Gramineae). An
      increase in the water depth significantly restrained the growth of both S.
      planiculumis and P. australis, while hydrological fluctuations did not obviously
      alter the growth of either species. In addition, both water depth and
      hydrological fluctuations significantly affected the interspecific interaction
      between these two wetland species. P. australis benefited from interspecific
      interaction under increasing water depth and hydrological fluctuations, and the
      RII values were clearly positive for plants grown at a water depth that
      fluctuated around 30 cm. The results may have some implications for understanding
      how S. planiculumis and P. australis, as well as wetland communities, respond to
      the natural variation or human modification of hydrological conditions.

PMID- 29379515
TI  - Molecular Epidemiology of Bacterial Wilt in the Madagascar Highlands Caused by
      Andean (Phylotype IIB-1) and African (Phylotype III) Brown Rot Strains of the
      Ralstonia solanacearum Species Complex.
AB  - The Ralstonia solanacearum species complex (RSSC) is a highly diverse cluster of
      bacterial strains found worldwide, many of which are destructive and cause
      bacterial wilt (BW) in a wide range of host plants. In 2009, potato production in
      Madagascar was dramatically affected by several BW epidemics. Controlling this
      disease is critical for Malagasy potato producers. The first important step
      toward control is the characterization of strains and their putative origins. The
      genetic diversity and population structure of the RSSC were investigated in the
      major potato production areas of the Highlands. A large collection of strains (n
      = 1224) was assigned to RSSC phylotypes based on multiplex polymerase chain
      reaction (PCR). Phylotypes I and III have been present in Madagascar for a long
      time but rarely associated with major potato BW outbreaks. The marked increase of
      BW prevalence was found associated with phylotype IIB sequevar 1 (IIB-1) strains
      (n = 879). This is the first report of phylotype IIB-1 strains in Madagascar. In
      addition to reference strains, epidemic IIB-1 strains (n = 255) were genotyped
      using the existing MultiLocus Variable-Number Tandem Repeat Analysis (MLVA)
      scheme RS2-MLVA9, producing 31 haplotypes separated into two related clonal
      complexes (CCs). One major CC included most of the worldwide haplotypes
      distributed across wide areas. A regional-scale investigation suggested that
      phylotype IIB-1 strains were introduced and massively spread via latently
      infected potato seed tubers. Additionally, the genetic structure of phylotype IIB
      1 likely resulted from a bottleneck/founder effect. The population structure of
      phylotype III, described here for the first time in Madagascar, exhibited a
      different pattern. Phylotype III strains (n = 217) were genotyped using the
      highly discriminatory MLVA scheme RS3-MLVA16. High genetic diversity was
      uncovered, with 117 haplotypes grouped into 11 CCs. Malagasy phylotype III
      strains were highly differentiated from continental African strains, suggesting
      no recent migration from the continent. Overall, population structure of
      phylotype III involves individual small CCs that correlate to restricted
      geographic areas in Madagascar. The evidence suggests, if at all, that African
      phylotype III strains are not efficiently transmitted through latently infected
      potato seed tubers.

PMID- 29379517
TI  - Effects of Age and Size on Xylem Phenology in Two Conifers of Northwestern China.
AB  - The climatic signals that directly affect the trees can be registered by xylem
      during its growth. If the timings and duration of xylem formation change,
      xylogenesis can occur under different environmental conditions and subsequently
      be subject to different climatic signals. An experimental design was applied in
      the field to disentangle the effects of age and size on xylem phenology, and it
      challenges the hypothesis that the timings and dynamics of xylem growth are size
      dependent. Intra-annual dynamics of xylem formation were monitored weekly during
      the growing seasons 2013 and 2014 in Chinese pine (Pinus tabulaeformis) and
      Qilian juniper (Juniperus przewalskii) with different sizes and ages in a semi
      arid region of northwestern China. Cell differentiation started 3 weeks earlier
      in 2013 and terminated 1 week later in 2014 in small-young pines than in big-old
      pines. However, differences in the timings of growth reactivation disappeared
      when comparing the junipers with different sizes but similar age. Overall, 77
      days were required for xylem differentiation to take place, but timings were
      shorter for older trees, which also exhibited smaller cell production. Results
      from this study suggest that tree age does play an important role in timings and
      duration of growth. The effect of age should also be considered to perform
      reliable responses of trees to climate.

PMID- 29379516
TI  - NtWRKY-R1, a Novel Transcription Factor, Integrates IAA and JA Signal Pathway
      under Topping Damage Stress in Nicotiana tabacum.
AB  - Topping damage can induce the nicotine synthesis in tobacco roots, which involves
      the activation of JA and auxin signal transduction. It remains unclear how these
      hormone signals are integrated to regulate nicotine synthesis. Here we isolated a
      transcription factor NtWRKY-R1 from the group IIe of WRKY family and it had
      strong negative correlation with the expression of putrescine N
      methyltransferase, the key enzyme of nicotine synthesis pathway. NtWRKY-R1 was
      specifically and highly expressed in tobacco roots, and it contains two
      transcriptional activity domains in the N- and C-terminal. The promoter region of
      NtWRKY-R1 contains two cis-elements which are responding to JA and auxin signals,
      respectively. Deletion of NtWRKY-R1 promoter showed that JA and auxin signals
      were subdued by NtWRKY-R1, and the expression of NtWRKY-R1 was more sensitive to
      auxin than JA. Furthermore, Yeast two-hybrid experiment demonstrated that NtWRKY
      R1 can interact with the actin-binding protein. Our data showed that the
      intensity of JA and auxin signals can be translated into the expression of NtWRKY
      R1, which regulates the balance of actin polymerization and depolymerization
      through binding actin-binding protein, and then regulates the expression of genes
      related to nicotine synthesis. The results will help us better understand the
      function of the WRKY-IIe family in the signaling crosstalk of JA and auxin under
      damage stress.

PMID- 29379518
TI  - Efficient Identification of Causal Mutations through Sequencing of Bulked F 2
      from Two Allelic Bloomless Mutants of Sorghum bicolor.
AB  - Sorghum (Sorghum bicolor Moench, L.) plant accumulates copious layers of epi
      cuticular wax (EW) on its aerial surfaces, to a greater extent than most other
      crops. EW provides a vapor barrier that reduces water loss, and is therefore
      considered to be a major determinant of sorghum's drought tolerance. However,
      little is known about the genes responsible for wax accumulation in sorghum. We
      isolated two allelic mutants, bloomless40-1 (bm40-1) and bm40-2, from a mutant
      library constructed from ethyl methane sulfonate (EMS) treated seeds of an
      inbred, BTx623. Both mutants were nearly devoid of the EW layer. Each bm mutant
      was crossed to the un-mutated BTx623 to generated F2 populations that segregated
      for the bm phenotype. Genomic DNA from 20 bm F2 plants from each population was
      bulked for whole genome sequencing. A single gene, Sobic.001G228100, encoding a
      GDSL-like lipase/acylhydrolase, had unique homozygous mutations in each bulked F2
      population. Mutant bm40-1 harbored a missense mutation in the gene, whereas bm40
      2 had a splice donor site mutation. Our findings thus provide strong evidence
      that mutation in this GDSL-like lipase gene causes the bm phenotype, and further
      demonstrate that this approach of sequencing two independent allelic mutant
      populations is an efficient method for identifying causal mutations. Combined
      with allelic mutants, MutMap provides powerful method to identify all causal
      genes for the large collection of bm mutants in sorghum, which will provide
      insight into how sorghum plants accumulate such abundant EW on their aerial
      surface. This knowledge may facilitate the development of tools for engineering
      drought-tolerant crops with reduced water loss.

PMID- 29379519
TI  - Exploring the Link between Nucleosome Occupancy and DNA Methylation.
AB  - Near promoters, both nucleosomes and CpG sites form characteristic spatial
      patterns. Previously, nucleosome depleted regions were observed upstream of
      transcription start sites and nucleosome occupancy was reported to correlate both
      with CpG density and the level of CpG methylation. Several studies imply a causal
      link where CpG methylation might induce nucleosome formation, whereas others
      argue the opposite, i.e., that nucleosome occupancy might influence CpG
      methylation. Correlations are indeed evident between nucleosomes, CpG density and
      CpG methylation-at least near promoter sites. It is however less established
      whether there is an immediate causal relation between nucleosome occupancy and
      the presence of CpG sites-or if nucleosome occupancy could be influenced by other
      factors. In this work, we test for such causality in human genomes by analyzing
      the three quantities both near and away from promoter sites. For data from the
      human genome we compare promoter regions with given CpG densities with genomic
      regions without promoters but of similar CpG densities. We find the observed
      correlation between nucleosome occupancy and CpG density, respectively CpG
      methylation, to be specific to promoter regions. In other regions along the
      genome nucleosome occupancy is statistically independent of the positioning of
      CpGs or their methylation levels. Anti-correlation between CpG density and
      methylation level is however similarly strong in both regions. On promoters,
      nucleosome occupancy is more strongly affected by the level of gene expression
      than CpG density or CpG methylation-calling into question any direct causal
      relation between nucleosome occupancy and CpG organization. Rather, our results
      suggest that for organisms with cytosine methylation nucleosome occupancy might
      be primarily linked to gene expression, with no strong impact on methylation.

PMID- 29379520
TI  - Notch Target Gene E(spl)mdelta Is a Mediator of Methylmercury-Induced Myotoxicity
      in Drosophila.
AB  - Methylmercury (MeHg) is a ubiquitous environmental contaminant and neurotoxicant
      that has long been known to cause a variety of motor deficits. These motor
      deficits have primarily been attributed to MeHg targeting of developing neurons
      and induction of oxidative stress and calcium dysregulation. Few studies have
      looked at how MeHg may be affecting fundamental signaling mechanisms in
      development, particularly in developing muscle. Studies in Drosophila recently
      revealed that MeHg perturbs embryonic muscle formation and upregulates Notch
      target genes, reflected predominantly by expression of the downstream
      transcriptional repressor Enhancer of Split mdelta [E(spl)mdelta]. An
      E(spl)mdelta reporter gene shows expression primarily in the myogenic domain, and
      both MeHg exposure and genetic upregulation of E(spl)mdelta can disrupt embryonic
      muscle development. Here, we tested the hypothesis that developing muscle is
      targeted by MeHg via upregulation of E(spl)mdelta using genetic modulation of
      E(spl)mdelta expression in combination with MeHg exposure in developing flies.
      Developmental MeHg exposure causes a decreased rate of eclosion that parallels
      gross disruption of indirect flight muscle (IFM) development. An increase in
      E(spl) expression across the pupal stages, with preferential E(spl)mdelta
      upregulation occurring at early (p5) stages, is also observed. E(spl)mdelta
      overexpression in myogenic lineages under the Mef2 promoter was seen to phenocopy
      eclosion and IFM effects of developmental MeHg exposure; whereas reduced
      expression of E(spl)mdelta shows rescue of eclosion and IFM morphology effects of
      MeHg exposure. No effects were seen on eclosion with E(spl)mdelta overexpression
      in neural and gut tissues. Our data indicate that muscle development is a target
      for MeHg and that E(spl)mdelta is a muscle-specific mediator of this myotoxicity.
      This research advances our knowledge of the target pathways that mediate
      susceptibility to MeHg toxicity, as well as a potential muscle development
      specific role for E(spl)mdelta.

PMID- 29379521
TI  - ir-HSP: Improved Recognition of Heat Shock Proteins, Their Families and Sub-types
      Based On g-Spaced Di-peptide Features and Support Vector Machine.
AB  - Heat shock proteins (HSPs) play a pivotal role in cell growth and variability.
      Since conventional approaches are expensive and voluminous protein sequence
      information is available in the post-genomic era, development of an automated and
      accurate computational tool is highly desirable for prediction of HSPs, their
      families and sub-types. Thus, we propose a computational approach for reliable
      prediction of all these components in a single framework and with higher accuracy
      as well. The proposed approach achieved an overall accuracy of ~84% in predicting
      HSPs, ~97% in predicting six different families of HSPs, and ~94% in predicting
      four types of DnaJ proteins, with bench mark datasets. The developed approach
      also achieved higher accuracy as compared to most of the existing approaches. For
      easy prediction of HSPs by experimental scientists, a user friendly web server ir
      HSP is made freely accessible at http://cabgrid.res.in:8080/ir-hsp. The ir-HSP
      was further evaluated for proteome-wide identification of HSPs by using proteome
      datasets of eight different species, and ~50% of the predicted HSPs in each
      species were found to be annotated with InterPro HSP families/domains. Thus, the
      developed computational method is expected to supplement the currently available
      approaches for prediction of HSPs, to the extent of their families and sub-types.

PMID- 29379522
TI  - Complexity Analysis of Resting-State fMRI in Adult Patients with Attention
      Deficit Hyperactivity Disorder: Brain Entropy.
AB  - Objective: Complexity analysis of functional brain structure data represents a
      new multidisciplinary approach to examining complex, living structures. I aimed
      to construct a connectivity map of visual brain activities using resting-state
      functional magnetic resonance imaging (fMRI) data and to characterize the level
      of complexity of functional brain activity using these connectivity data.
      Methods: A total of 25 healthy controls and 20 patients with attention deficit
      hyperactivity disorder (ADHD) participated. fMRI preprocessing analysis was
      performed that included head motion correction, temporal filtering, and spatial
      smoothing process. Brain entropy (BEN) was calculated using the Shannon entropy
      equation. Results: My findings demonstrated that patients exhibited reduced brain
      complexity in visual brain areas compared to controls. The mean entropy value of
      the ADHD group was 0.56 +/- 0.14, compared to 0.64 +/- 0.11 in the control group.
      Conclusion: My study adds an important novel result to the growing literature
      pertaining to abnormal visual processing in ADHD that my ADHD patients had lower
      BEN values, indicating more-regular functional brain structure and abnormal
      visual information processing.

PMID- 29379523
TI  - Melatonin and Angelman Syndrome: Implications and Mathematical Model of Diurnal
      Secretion.
AB  - The main aim of the study was to compare the melatonin rhythms in subjects with
      Angelman syndrome (n = 9) and in children with (n = 80) and without (n = 40)
      epilepsy (nonepileptic patients diagnosed with peripheral nerve palsies,
      myopathy, and back pain) using our mathematical model of melatonin circadian
      secretion. The characteristics describing the diurnal hormone secretion such as
      minimum melatonin concentration, release amplitude, phase shift of melatonin
      release, and sleep duration as well as the dim light melatonin onset (DLMO) of
      melatonin secretion and the gamma shape parameter allow analyzing the fit and
      deducing about how much the measured melatonin profile differs from a
      physiological bell-shaped secretion. The estimated sleep duration and phase shift
      of melatonin release as well as the DMLO offsets at 25% and 50% relative
      thresholds are the key characteristic of Angelman syndrome children. As revealed
      from the gamma shape parameter, the melatonin secretion profiles are disturbed in
      majority of the AG subjects revealing rather a triangular course instead of the
      bell-like one.

PMID- 29379524
TI  - Management of Intractable Nasal Hyperreactivity by Selective Resection of
      Posterior Nasal Nerve Branches.
AB  - The posterior nasal nerves emerge from the sphenopalatine foramen and contain
      sensory and autonomic nerve components. Posterior nasal neurectomy is an
      effective method to remove pathological neural networks surrounding the inferior
      turbinate that cause unregulated nasal hypersensitivity with excess secretion in
      patients with severe allergic rhinitis (AR). We describe the sophisticated
      endoscopic surgical procedure that allows feasible access to the confined area
      and selective resection of the nerve branches with the preservation of the
      sphenopalatine artery (SPA). We retrospectively analyzed the cases of 23
      symptomatic severe AR patients who failed to respond to standard medical
      treatment and underwent surgery. There have been no major complications after
      surgery including nasal bleeding or transient numbness of the upper teeth. The
      mean total nasal symptom scores (TNSS) were decreased by 70.2% at 12 months after
      the procedure. Our comparison of the clinical effectiveness based on the number
      of severed nerve branches revealed that the improvement of the TNSS was
      significantly higher in patients with >2 branches. We conclude that this
      minimally invasive technique that preserves the SPA is clinically useful and
      decreases the rate of postoperative complications. This trial is registered with
      UMIN000029025.

PMID- 29379526
TI  - Performance Evaluation of Commercial Dengue Diagnostic Tests for Early Detection
      of Dengue in Clinical Samples.
AB  - The shattering rise in dengue virus infections globally has created a need for an
      accurate and validated rapid diagnostic test for this virus. Rapid diagnostic
      test (RDT) and reverse transcription-polymerase chain reaction (RT-PCR)
      diagnostic detection are useful tools for diagnosis of early dengue infection. We
      prospectively evaluated the diagnostic performance of nonstructural 1 (NS1) RDT
      and real-time RT-PCR diagnostic kits in 86 patient serum samples. Thirty-six
      samples were positive for dengue NS1 antigen while the remaining 50 were negative
      when tested with enzyme-linked immunosorbent assay (ELISA). Commercially
      available RDTs for NS1 detection, RTK ProDetectTM, and SD Bioline showed high
      sensitivity of 94% and 89%, respectively, compared with ELISA. GenoAmp(r)
      Trioplex Real-Time RT-PCR and RealStar(r) Dengue RT-PCR tests presented a
      comparable kappa agreement with 0.722. The result obtained from GenoAmp(r) Real
      Time RT-PCR Dengue test showed that 14 samples harbored dengue virus type 1 (DENV
      1), 8 samples harbored DENV-2, 2 samples harbored DENV-3, and 1 sample harbored
      DENV-4. 1 sample had a double infection with DENV-1 and DENV-2. The NS1 RDTs and
      real-time RT-PCR tests were found to be a useful diagnostic for early and rapid
      diagnosis of acute dengue and an excellent surveillance tool in our battle
      against dengue.

PMID- 29379525
TI  - (Mesenchymal) Stem Cell-Based Therapy in Cisplatin-Induced Acute Kidney Injury
      Animal Model: Risk of Immunogenicity and Tumorigenicity.
AB  - Pathogenesis of AKI is complex and involves both local events in the kidney as
      well as systemic effects in the body that are interconnected and interdependent.
      Despite intensive investigations there is still no pharmacological agent that
      could provide complete protection against cisplatin nephrotoxicity. In the last
      decade mesenchymal stem cells (MSCs) have been proposed as a potentially useful
      therapeutic strategy in various diseases, including acute kidney injury. Although
      MSCs have potent immunosuppressive properties, animal studies also suggest that
      transplanted MSCs may elicit immune response. Interestingly, tumorigenicity of
      transplanted MSCs in animal studies has been rarely studied. Since the risk of
      tumorigenicity of particular therapy as well as the immune response to solid or
      cell grafts is a major issue in clinical trials, the aim of the present paper is
      to critically summarize the results of MSC transplantation on animal models of
      AKI, particularly cisplatin-induced animal models, and to expose results and main
      concerns about immunogenicity and tumorigenicity of transplanted MSCs, two
      important issues that need to be addressed in future studies.

PMID- 29379527
TI  - Clinical and Mortality Risk Factors in Bloodstream Infections with Carbapenem
      Resistant Enterobacteriaceae.
AB  - Objective: To investigate the risk factors underlying the occurrence and
      mortality of bloodstream infections (BSIs) with carbapenem-resistant
      Enterobacteriaceae (CRE). Methods: Medical information was retrospectively
      analyzed from 148 cases of patients with Enterobacteriaceae BSIs at a medical
      center in China, between 2013 and 2015. Results: The 30-day mortality rate in the
      CRE group was 65.4%. Indwelling urethral catheterization, admission to the ICU,
      use of antibiotics within 30 days, and BSIs from the respiratory system were
      associated with CRE BSIs. Lung infection, abdominal infection, central venous
      catheterization, and use of hormones within 30 days were associated with
      mortality. Conclusion: The 30-day mortality rate of CRE BSIs was high. Lung
      infections, abdominal infections, central venous catheterization, and use of
      hormones within 30 days increased the mortality rate of Enterobacteriaceae BSIs.

PMID- 29379529
TI  - Is there a rapid increase in prevalence of obesity in Polish children? An 18-year
      prospective observational study in Gdansk, Poland.
AB  - Introduction: The prevalence of overweight and obesity is not regularly screened
      among Polish children. Very few longitudinal data exist on the prevalence and
      increase of overweight and obesity in this population. The aim of the study was
      to analyze the prevalence of overweight and obesity among selected age categories
      of children from Gdansk, on the basis of 1992-2012 data. Material and methods:
      The anthropometric data (body weight and height, body mass index) of 70,329
      children aged between 6 and 13 years were analyzed. Data were collected during
      annually performed child health measurements in schools by medical staff of
      Gdansk Center for Health Promotion during 1992-2012. Results: No constant trend
      to increase or decrease in the prevalence of overweight or obesity was documented
      in any of the studied age groups (p > 0.05). An age-related increase in the
      prevalence of overweight and obesity was observed throughout all consecutive age
      categories in boys and in prepubertal girls (p < 0.05). Overweight and obesity
      were significantly more frequent in girls than in boys from all age categories (p
      < 0.05), except 12- and 13-year-old children (p = 0.173; p = 0.973), in whom no
      gender-specific differences were documented. Conclusions: Our study did not
      confirm the previously reported growing tendency in the prevalence of overweight
      and obesity among children. However, our findings point to an age-related
      increase in the prevalence of excess body weight in the pediatric population.

PMID- 29379530
TI  - Relationship between urine lipid peroxidation, anthropometric parameters and
      parameters associated with goitre formation in school-age children.
AB  - Introduction: Oxidative stress has been implicated in the normal ageing process
      and the pathogenesis of several diseases, including goitre. The aim of the study
      was to evaluate the relationship between urine lipid peroxidation (LPO) and
      anthropometric parameters as well as the parameters associated with goitre
      formation in children. Material and methods: The subjects included 172 healthy
      children (93 girls and 79 boys) aged 8-15, divided into 4 age groups - group I (8
      9 years), group II (10-11 years), group III (12-13 years) and group IV (14-15
      years) - and into 2 groups based on the BSA: the BSA-1 group (<= 0.55 m2) and the
      BSA-2 group (> 0.55 m2). Results: The value of LPO was the highest in group I but
      the difference between the groups was not statistically significant (p = 0.074).
      In the BSA-1 group, the LPO was higher than in the BSA-2 group (12.75 +/-6.90
      nmol/ml and 10.79 +/-4.86 nmol/ml, respectively; p = 0.023). We found a weak,
      negative linear correlation between LPO and age (r = -0.216; p < 0.005), body
      mass (r = -0.153; p < 0.05), height (r = -0.152; p < 0.05) and BSA (r = -0.151; p
      < 0.05). Conclusions: Anthropometric parameters of school-age children
      independently of age are negatively associated with oxidative damage to membrane
      lipids, whereas factors promoting goitrogenesis do not contribute to this
      process.

PMID- 29379531
TI  - An assessment of health status and health behaviours in adolescents: main points
      and methods of the SOPKARD-Junior programme.
AB  - Introduction: The study involved preparing and implementation a model of complex
      screening programme for adolescents and comparison of anthropometric examinations
      between the population of the SOPKARD-Junior programme and representative sample
      of Polish children in the same age. Material and methods: The screening programme
      in 14-15 year old pupils (n = 282) included: anthropometric, blood pressure,
      echocardiographic, electrocardiographic, carotid arteries, kidney and thyroid
      ultrasound examinations, as well as respiratory, dental and masticatory system,
      orthopaedic, psychological and psychiatric assessment. Blood and urine tests were
      also performed. The results of anthropometric examinations from the SOPKARD
      Junior and OLAF programmes were used for comparative analysis. Results:
      Statistically significant (p < 0.001) differences between young people from Sopot
      and their peers in the general Polish population were found in height (+3.61 cm
      for boys), body mass (+5.19 kg for boys and +3.99 kg for girls), body mass index
      (+0.99 kg/m2 for boys and +1.33 kg/m2 for girls), waist circumference (+4.52 cm
      for boys and +4.52 cm for girls) and hip circumference (+2.51 cm for boys). The
      highest attendance rate was achieved for examinations performed in school (e.g.
      anthropometric and blood pressure measurements - n = 268; 95%) and the lowest for
      the echocardiograpy performed in local hospital (n = 133; 47%). The mean score of
      the programme quality (scale 1-6) assessed by children was 4.63. Conclusions: The
      SOPKARD-Junior programme represents an attempt to develop a model of screening
      assessments for teenagers in Poland. Preliminary results of the SOPKARD-Junior
      programme indicate small differences in the biological development of Sopot youth
      in comparison with their peers from Polish population of the OLAF programme. The
      high attendance rate on research conducted at the school indicate that proposed
      health examinations in adolescents are acceptable and feasible.

PMID- 29379528
TI  - Hypercholesterolaemia - practical information for non-specialists.
AB  - Hypercholesterolaemia is amongst the most common conditions encountered in the
      medical profession. It remains one of the key modifiable cardiovascular risk
      factors and there have been recent advances in the risk stratification methods
      and treatment options available. In this review, we provide a background into
      hypercholesterolaemia for non-specialists and consider the merits of the
      different risk assessment tools available. We also provide detailed
      considerations as to: i) when to start treatment, ii) what targets to aim for and
      iii) the role of low density lipoprotein cholesterol.

PMID- 29379532
TI  - Parental knowledge and metabolic control of children and young adults with type 1
      diabetes.
AB  - Introduction: The authors aimed to answer the following questions: 1) What level
      of knowledge of type 1 diabetes do the parents of children and young adults with
      this disease have? 2) Will this level of knowledge increase after 1 year of
      observation? 3) Does improving the knowledge of young adults and their parents
      result in better metabolic control of the patients? Material and methods: This
      study included 227 patients between the ages of 5 and 20 years with type 1
      diabetes. The research was conducted from March 2009 to June 2011. The following
      two time points were examined: the beginning of the study (test 1a) and one year
      later (test 1b). The knowledge levels of the patients and parents were obtained
      using a survey and a knowledge test. Results: Comparison of the results from the
      two study time points showed that the respondents had a significantly higher
      level of knowledge after 1 year (p = 0.001). The comparison of glycated
      hemoglobin levels between the two time points in patients with type 1 diabetes
      revealed that the levels were significantly higher at test 1b compared to test 1a
      (p = 0.0005). Conclusions: The parents of children and young adults with type 1
      diabetes demonstrate a satisfactory level of theoretical knowledge of therapeutic
      conduct and self-monitoring principles. The test 1b results demonstrated a higher
      level of theoretical knowledge in all respondents and poorer metabolic control.
      Poorer metabolic control in some patients suggests that metabolic control in type
      1 diabetes depends on factors other than education. Further research is necessary
      to determine these additional factors.

PMID- 29379533
TI  - Winter ambient training conditions are associated with increased bronchial
      hyperreactivity and with shifts in serum innate immunity proteins in young
      competitive speed skaters.
AB  - Introduction: Regular training modulates airway inflammation and modifies
      susceptibility to respiratory infections. The impact of exercise and ambient
      conditions on airway hyperreactivity and innate immunity has not been well
      studied. We aimed to assess exercise-related symptoms, lung function, airway
      hyperresponsiveness and innate immunity proteins in relation to meteorological
      conditions and exercise load in competitive athletes. Material and methods:
      Thirty-six speed skaters were assessed during winter (WTP) and summer (STP)
      periods. The control group comprised 22 non-exercising subjects. An allergy
      questionnaire for athletes (AQUA) and IPAQ (International Physical Activity
      Questionnaire) were used to assess symptoms and exercise. Meteorological
      parameters were acquired from World Meteorological Organization resources. Serum
      innate immunity proteins were measured by ELISA. Results: Exercise-associated
      respiratory symptoms were reported by 79.4% of skaters. Despite similar exercise
      load and lung parameters during both periods, positive methacholine challenge was
      more frequent during winter (p = 0.04). Heat shock protein HSPA1 and IL-1RA were
      significantly decreased during STP compared to WTP and controls. During WTP, IL
      1RA was elevated in skaters reporting exercise-induced symptoms (p = 0.007).
      sCD14 was elevated in athletes versus controls in both periods (p < 0.05). HSPA1
      was significantly higher in WTP compared to STP irrespective of presence of
      respiratory tract infections (RTIs). IL-1RA in WTP was elevated versus STP (p =
      0.004) only in RTI-negative athletes. Serum IL-1RA negatively correlated with
      most meteorological parameters during WTP. Conclusions: Ambient training
      conditions, but not training load, influence bronchial hyperreactivity and the
      innate immune response in competitive athletes assessed during winter. The
      protective effect of regular exercise against respiratory infections is
      associated with a shift in serum innate immunity proteins.

PMID- 29379534
TI  - Stool antigen detection versus 13C-urea breath test for non-invasive diagnosis of
      pediatric Helicobacter pylori infection in a limited resource setting.
AB  - Introduction: The prevalence of childhood infection with Helicobacter pylori is
      high, especially in developing countries. Non-invasive methods for detection of
      infection in children should be inexpensive, easy to perform, well tolerated and
      have a high diagnostic accuracy. We aimed to compare the reliability, specificity
      and sensitivity of the H. pylori stool antigen (HpSA) test with the 13C-urea
      breath test (13C-UBT) for the diagnosis of H. pylori infection in a limited
      resource setting. Material and methods: The stool samples of 60 symptomatic and
      dyspeptic children with a mean age of 7.2 +/-3.7 years (2-15 years) were
      evaluated using the rapid One step HpSA test by lateral flow immunoassay. The 13C
      UBT was used as the gold standard method for the diagnosis of H. pylori
      infection. Results: The HpSA test detected H. pylori antigen in 34 out of 38
      positive patients with 4 false-negatives (sensitivity 89.5%, 95% confidence
      interval (CI): 75.2-97.1%), while 21 patients had true-negative results and one
      false-positive (specificity 95.5%, 95% CI: 77.2-99.9%), with a strong measure of
      agreement between the HpSA test and the 13C-UBT (kappa = 0.83, 95% CI: 68-97%, p
      < 0.001). It had a positive predictive value of 97.1% (95% CI: 85.1-99.9%), a
      negative predictive value of 84% (95% CI: 63.9-95.5%) and an accuracy of 91.7%.
      Conclusions: The rapid lateral flow HpSA test is a reliable method for the
      primary diagnosis of H. pylori infections in children, though not as accurate as
      the 13C-UBT. It is more affordable, simpler to perform and more tolerable,
      representing a viable alternative, especially in developing countries.

PMID- 29379535
TI  - Diagnostic yield of esophagogastroduodenoscopy in children with chronic abdominal
      pain.
AB  - Introduction: Chronic abdominal pain (CAP) is one of the most common indications
      of esophagogastroduodenoscopy (EGD) in the pediatric population. However, there
      is not enough information about the diagnostic yield of EGD in children with CAP.
      We aimed to evaluate the diagnostic yield of EGD in children with CAP in the
      Eastern Black Sea region of Turkey. Material and methods: The study included
      children (n = 372) who underwent EGD for the primary indication of chronic
      abdominal pain during an 18-month period. We collected data on demographic
      features (age, sex), clinical characteristics (alarm symptoms), and EGD results
      for each patient. Results: Patients' mean age was 13 years (range: 4-17 years;
      mean +/- SD: 12.65 +/-3.39 years), and the majority were female (n = 234, 62.9%).
      Endoscopy was diagnostic in 209 patients (56.2%; 95% CI: 30.35-40.05%). The most
      common diagnosis was Helicobacter pylori gastritis (35.2%) followed by reflux
      esophagitis. Significantly greater diagnostic yield of EGD was determined in
      patients with alarm symptoms (65.1%) compared to those without (45.2%) (OR =
      2.26, 95% CI: 1.49-3.44, p = 0.001). Conclusions: We determined a high diagnostic
      yield of EGD in children with CAP. Although the diagnostic yield of EGD in the
      assessment of CAP was found to be higher in the presence of alarm symptoms, a
      significant number of children without alarm symptoms were also found to have
      gastrointestinal system pathology diagnosed by EGD.

PMID- 29379536
TI  - Bifidobacteria and lactobacilli in the gut microbiome of children with non
      alcoholic fatty liver disease: which strains act as health players?
AB  - Introduction: Non-alcoholic fatty liver disease (NAFLD), considered the leading
      cause of chronic liver disease in children, can often progress from non-alcoholic
      fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that
      obesity is one of the main risk factors involved in NAFLD pathogenesis, even if
      specific mechanisms have yet to be elucidated. We investigated the distribution
      of intestinal bifidobacteria and lactobacilli in the stools of four groups of
      children: obese, obese with NAFL, obese with NASH, and healthy, age-matched
      controls (CTRLs). Material and methods: Sixty-one obese, NAFL and NASH children
      and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters
      were measured for all subjects. All children with suspected NASH underwent liver
      biopsy. Bifidobacteria and lactobacilli were analysed in children's faecal
      samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut
      microbiome. Results: Three Bifidobacterium spp. (Bifidobacterium longum,
      Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus
      spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently
      recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or
      obese children compared to CTRLs. Particularly, L. mucosae was significantly
      higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in
      CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting
      a protective and beneficial role of these microorganisms against the
      aforementioned diseases. Conclusions: Bifidobacteria seem to have a protective
      role against the development of NAFLD and obesity, highlighting their possible
      use in developing novel, targeted and effective probiotics.

PMID- 29379537
TI  - Hydrogen excretion in pediatric lactose malabsorbers: relation to symptoms and
      the dose of lactose.
AB  - Introduction: Lactose malabsorption arises from lactase deficiency and may lead
      to lactose intolerance - gastrointestinal symptoms after lactose ingestion.
      Occurrence and severity of the symptoms are influenced by many factors, including
      the dose of lactose and the intensity of its colonic fermentation to short chain
      fatty acids and gases. Material and methods: The hydrogen breath test (HBT) after
      30 g or 50 g of lactose was performed in 387 children. Further analysis included
      children who had a positive HBT result. The HBT parameters were net hydrogen
      concentration in each breath and total net hydrogen concentration during the HBT.
      The time of the first hydrogen rise was also calculated. HBT parameters were
      analyzed according to symptoms occurrence (lack or present), symptoms severity
      (lack, moderate or severe) and the dose of lactose (30 g or 50 g). Results: One
      hundred and six children (12.1 years, 46 boys) had a positive HBT result.
      Symptoms occurrence was positively related to net hydrogen concentration at 30
      min, 60 min and 90 min (p < 0.001 at each time point), as well as to the total
      net hydrogen concentration (p < 0.001). There were no differences in hydrogen
      excretion between subjects with moderate and severe symptoms after lactose
      ingestion. Symptoms were more frequent in subjects given 50 g of lactose than in
      those given 30 g of lactose (79% vs. 47%, p = 0.003). In both dose groups
      symptoms occurrence was related to hydrogen excretion. Conclusions: Symptoms
      occurrence is closely related to hydrogen excretion and to the dose of ingested
      lactose.

PMID- 29379538
TI  - Histologic recovery among children with celiac disease on a gluten-free diet. A
      long-term follow-up single-center experience.
AB  - Introduction: Celiac disease (CD) is defined by gluten-induced immune-mediated
      enteropathy, affecting approximately 1% of the genetically predisposed
      population. The immunologic response to gluten causes characteristic intestinal
      alterations with gradual development. Histologic recovery of intestinal
      architecture was reported to occur within 6-12 months after starting a gluten
      free diet, simultaneously with clinical remission. The aim of this study was to
      assess the rate and timing of histologic recovery among children with CD on a
      gluten-free diet, diagnosed and followed in an academic referral pediatric center
      during a 10-year period. Material and methods: 105 biopsy-confirmed CD children
      underwent follow-up small intestinal biopsies within at least 1 year after
      dietary gluten withdrawal. Further biopsies were performed if villous alterations
      were persistent. The Marsh classification modified by Oberhuber was used to score
      the histologic injuries. Results: In all 19 cases with Marsh type II at
      diagnosis, villous alterations normalized to Marsh type 0 within the first year.
      From 86 children enrolled with Marsh type III lesions, histologic remission was
      observed in 81.4% after 1 year, 91.8% within 2-3 years and 97.6% in long-term
      follow up (>= 3 years). Two (2.3%) patients with concomitant selective IgA
      deficiency had symptoms of malabsorption and persisting villous atrophy lasting
      more than 3 years despite a gluten-free diet. There was a significant statistic
      difference between the proportion of children with Marsh type IIIA, type IIIB and
      Marsh type IIIC respectively that achieved histologic recovery within 1 to 2
      years after gluten withdrawal. There were more children with partial 25 (92.6%)
      and subtotal villous atrophy 30 (88.2%) showing histologic improvement, compared
      to only 15 (60%) patients with total villous atrophy that recovered within the
      first 2 years of diet (p = 0.01 and p = 0.02 respectively). Conclusions:
      Histologic recovery in CD after starting a gluten-free diet in children takes at
      least 1 year and might be incomplete only in a small proportion of children,
      mainly associated with IgA immunodeficiency. Systematic follow-up of children
      with CD and persistent malabsorption syndrome is needed in order to avoid
      secondary complications.

PMID- 29379539
TI  - Enteric parasites can disturb leptin and adiponectin levels in children.
AB  - Introduction: Infection by intestinal parasites in childhood may be the main
      cause of many health-related problems in developed countries such as anemia,
      anorexia, loss of appetite, retarded growth and development. The aim of the
      present study was to assess the effect of different intestinal parasites on white
      adipose tissue hormones. Material and methods: Eighty-one children infected by
      different parasites and 35 apparently healthy children were enrolled in this
      study. All patients and controls were subjected to clinical examination,
      measurement of body mass index (BMI) and laboratory examination. Results: For BMI
      percentiles, there was a significant increase in serum leptin level (p = 0.042)
      and a significant decrease in serum adiponectin level (p = 0.039) in uninfected
      children, whereas there were no significant changes in the infected group (p =
      0.068 and 0.082 respectively). A significant increase in leptin and decrease in
      adiponectin levels were observed for E. histolytica, Strongyloides and E.
      histolytica and Giardia infections compared to the control group (p = 0.047,
      0.035 and 0.019 for leptin, and p = 0.025, 0.038 and 0.041 for adiponectin,
      respectively). Conclusions: The infection by some intestinal parasites may
      deregulate the secretion of leptin and adiponectin and also affect the absorption
      of some nutrients which can disturb the BMI and cause anorexia.

PMID- 29379540
TI  - Prognostic value of assessment of stool and serum IL-1beta, IL-1ra and IL-6
      concentrations in children with active and inactive ulcerative colitis.
AB  - Introduction: Interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL
      1ra) and interleukin-6 (IL-6) contribute to the pathogenesis of ulcerative
      colitis (UC). The aim of our study was to evaluate the serum and stool IL-1beta,
      IL-1ra and IL-6 concentrations as potential prognostic factors in children with
      UC. Material and methods: Thirty-eight children with UC (20 active, 18 inactive)
      and 14 healthy controls were prospectively included in the study. IL-1beta, IL
      1ra and IL-6 concentrations were measured in serum and stool supernatants at
      inclusion to the study using ELISA immunoassays. The children were followed up
      over 5 years, and at each follow-up clinical disease activity, quantity and
      severity of relapses, nutritional status, endoscopic and histopathologic
      activity, disease complications and the treatment regimen were evaluated.
      Results: In children with active and inactive UC who had relapsed during a 5-year
      follow-up period compared to the non-relapse groups we found significantly
      increased serum IL-1beta (1.34 vs. 0.98 pg/ml, p < 0.05, and 1.02 vs. 0.68 pg/ml,
      p < 0.01, respectively,) and IL-1ra (718.0 vs. 453.2 pg/ml, p < 0.05, and 567.4
      vs. 365.1 pg/ml, p < 0.01, respectively). Additionally, in children who had
      experienced complications during a 5-year follow-up period we observed
      significantly increased serum and stool IL-1beta (p < 0.05) and serum IL-1ra (p <
      0.01) compared to the group without complications. Conclusions: We concluded that
      serum IL-1beta and IL-1ra and to a lesser extend stool IL-1beta concentrations
      may be useful prognostic factors in children with active and inactive UC over a
      short-term follow-up period, which may help to identify children that require
      more aggressive therapy due to an increased risk of relapse or complications
      resulting from UC.

PMID- 29379541
TI  - Vitamin D deficiency is associated with urinary tract infection in children.
AB  - Introduction: In humans, vitamin D has been shown to play a role in infectious
      diseases, but its association with acquisition and a complicated course of
      febrile urinary tract infections (UTIs) has not been investigated. We aimed to
      investigate the association between 25-hydroxyvitamin D (25(OH)D3) levels and the
      risk of first time febrile UTI in children. Material and methods: This
      prospective case-control study included 50 children with first febrile UTI, with
      no risk factors for UTI, and 50 age- and sex-matched healthy siblings as
      controls. White blood cell count, serum C-reactive protein, calcium, phosphorus,
      alkaline phosphatase and parathormone were measured in all studied children.
      Vitamin D status was determined by measuring plasma 25(OH)D3 level. Deficiency
      was defined as a plasma 25(OH)D3 level <= 25 nmol/l. Results: Children with UTI
      had significantly lower mean serum levels of 25(OH)D3 (10.5 +/-2.7 nmol/l) than
      those of controls (25.9 +/-5.6 nmol/l) (p < 0.05). Patients with lower UTI had
      significantly higher serum levels of 25(OH)D3 compared to those with acute
      pyelonephritis (12.4 +/-2.59 vs. 8.2 +/-3.2 nmol/l; p < 0.001). Mean serum levels
      of 25(OH)D3 were significantly lower (p = 0.001) in the female patients compared
      with males, and this difference was not found within the control group.
      Multivariate analysis showed that a serum 25(OH)D3 level of <= 25 nmol/l is
      associated with UTI (OR = 1.94, 95% CI: 1.61-2.82; p = 0.04). Conclusions:
      Vitamin D deficiency (<= 25 nmol/l) was an independent risk factor for UTI in
      children.

PMID- 29379542
TI  - Clinical and immunological effects of vitamin D supplementation during the pollen
      season in children with allergic rhinitis.
AB  - Introduction: Vitamin D deficiency has been proposed as a potential contributing
      factor in patients with allergic diseases. We compared the clinical and
      immunological effects of vitamin D supplementation to placebo during the pollen
      season in children with allergic rhinitis. Material and methods: Thirty-eight
      children aged 5-12, sensitive to grass pollen, participated in a prospective,
      randomized, double-blind, placebo-controlled trial. Children received either
      vitamin D 1000 IU daily supplementation or placebo. We studied
      symptoms/medication score, lung function, exhaled nitric oxide concentration
      (FENO), methacholine bronchial provocation test and serum level of 25(OH)D, as
      well as; CD4+CD25+Foxp3+ cells, TLR4, IL-1, IL-6, TNF and the IL-10 and
      transforming growth factor beta1 (TGF-beta1) levels in cell culture supernatants.
      Results: Vitamin D therapy was effective in reduction of the symptoms/medication
      score (p = 0.0371). In vitamin D group an increase in the CD4+CD25+Foxp3+ cells
      (7.06 vs. 10.5%; p = 0.0013) and serum 25(OH)D concentration (49.6 vs. 96.6
      ng/ml; p = 0.0001) and in control group an increase in FENO (15.6 vs. 21 ppb; p =
      0.0331) and serum 25(OH)D level were observed (82.9 vs. 100.3 ng/ml; p =
      0.0003).We revealed a higher increase from baseline in the percentage of
      CD4+CD25+Foxp3+ cells in the vitamin D group compared to the control group (p =
      0.0058). A significant correlation between CD4+CD25+Foxp3+ cell induction and
      FENO reduction in the vitamin D group was observed (p = 0.0217). Conclusions:
      Vitamin D 1000 IU as a supplementary treatment of grass pollen allergy in
      children with allergic rhinitis during the pollen season significantly reduced
      the symptoms/medication score. The study revealed an immunological effect of
      vitamin D.

PMID- 29379543
TI  - Usefulness of molecular diagnosis in egg allergic children.
AB  - Introduction: Egg allergy is one of the most common food allergies in children.
      Egg white, including ovomucoid (OVM or Gal d 1) and ovalbumin (OVA or Gal d 2),
      is the major source of allergens. The aim of this study was to assess the role of
      Gal d 1 and Gal d 2 in predicting the risk of anaphylaxis caused by eggs in
      children, and to compare this new diagnostic tool with established methods of
      allergen-specific IgE detection. Material and methods: One hundred and forty
      eight children were divided into 2 groups according to a positive (group A, 33
      children) or negative (group B, 115 children) history of anaphylaxis after
      ingestion/contact with eggs. All patients underwent an allergological evaluation
      by measurements of specific IgE against egg white: Gal d 1 and Gal d 2. Results:
      Higher levels of Gal d 1, Gal d 2 and IgE against egg white were detected in
      group A compared to group B (p < 0.001). Although the area under the curve was
      similar for Gal d 1 and Gal d 2, egg white specific IgE showed a better
      sensitivity (85%) for a cut-off value >= 0.975 kUA/l, while Gal d 1 and Gal d 2
      demonstrated a better specificity (90% and 80%, respectively) for cut-off values
      >= 1.460 kUA/l and >= 2.310 kUA/l, respectively. Conclusions: Egg white specific
      IgE showed a similar ability as Gal d 1 and Gal d 2 in differentiating children
      at risk for egg anaphylaxis, although Gal d 1 and Gal d 2 showed a better
      specificity.

PMID- 29379544
TI  - The influence of various therapeutic regimens on early clinical and laboratory
      response and outcome of children with secondary hemophagocytic
      lymphohistiocytosis.
AB  - Introduction: Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life
      threatening syndrome of severe hyperinflammation which is often triggered by
      infection or autoimmune disease (macrophage activation syndrome - MAS). The aim
      of our study was to assess the frequency of sHLH/MAS in children treated in our
      institution and to compare the effectiveness of various therapeutic
      interventions. Material and methods: Between 2005 and 2013, 24 children (age: 1
      17 years) were consecutively treated for sHLH/MAS. Therapy was based on
      glucocorticoids (GCs) in high or standard doses (hd-GCs or sd-GCs), intravenous
      immunoglobulin (IVIG), and cyclosporin A (CyA). A comparison of selected
      laboratory and clinical parameters during the first 72 h of treatment and after a
      week from the last intervention applied in the first 72 h after diagnosis was
      performed retrospectively. Results: The majority of patients (14/24, 58%)
      suffered from sHLH/MAS in the course of an autoimmune disease (12 patients
      diagnosed with a systemic form of juvenile idiopathic arthritis). We found with a
      confidence level of 95% that the application of hd-GCs in the first 24 h caused
      rapid alleviation of fever, reduction of hepatosplenomegaly, and an increase in
      thrombocytes and s-fibrinogen concentrations. The use of combination therapy with
      hd-GCs, IVIG, and CyA in the first 72 h caused a faster increase in s-fibrinogen.
      All patients survived and were alive at the follow-up of 1-8 years. Conclusions:
      The results indicate that treatment of sHLH/MAS based on hd-GCs, CyA and IVIG is
      an effective therapy in children.

PMID- 29379546
TI  - GABRG2 C588T gene polymorphisms might be a predictive genetic marker of febrile
      seizures and generalized recurrent seizures: a case-control study in a Romanian
      pediatric population.
AB  - Introduction: This case-control study aimed to assess two single nucleotide
      polymorphisms of the gene encoding the GABRG2 protein - GABRG2 (3145 G>A) and
      GABRG2 rs 211037 Asn196Asn (C588T) - in a cohort of pediatric patients from
      Romania, and evaluate their possible impact on drug-resistant forms of
      generalized epilepsy and recurrent febrile seizures. Material and methods: One
      hundred and fourteen children with idiopathic generalized epilepsy (group 1) or
      febrile seizures (group 2) were compared to 153 controls. Peripheral blood
      samples were assessed using polymerase chain reaction-restriction fragment length
      polymorphism analysis, with results interpreted based on the disappearance of a
      restriction site in the C allele (122 bp) compared to the T allele (100 bp + 22
      bp). Results: A significant association was found with the TT homozygous genotype
      and T allele for both febrile seizures and epilepsy for the C588T locus, while
      GABRG2 G>A 3145 showed no significant association with any type of seizure. The
      TT homozygous genotype of GABRG2 Asn196Asn polymorphism was more frequent in
      patients with a history of febrile seizures (p = 0.0001), without a significant
      association identified for GABRG2-G>A 3145. Composite analysis showed
      associations with epilepsy for CC-AG (p = 0.02) and CT-AG (p = 0.007) with the CC
      AA combination as reference. Conclusions: C588T polymorphism of the GABRG2 gene
      might be a predictive genetic marker in triggering febrile convulsions. GABRG2
      rs211037 TT homozygotes and T allele variants have an increased risk for
      developing febrile seizures. Recurrent crises and repeated episodes of seizures
      are more frequent in the GABRG2 Asn196Asn TT genotype polymorphism, with a 45 and
      8 times higher risk of developing idiopathic generalized epilepsy and recurrent
      febrile seizures, respectively.

PMID- 29379545
TI  - Augmented mitochondrial cytochrome c oxidase activity in children with iron
      deficiency: a tandem between iron and copper?
AB  - Introduction: Dyshomeostasis of essential trace elements including iron and
      copper plays a key role in the pathogenesis of a myriad of serious conditions
      including iron deficiency (ID) anemia, in which impaired cellular energy
      metabolism is prominent. Although experimental studies documented decreased
      activity of cytochrome c oxidase (CytOx) in ID, there are not enough clinical
      data. The present study was conducted to determine serum copper levels and
      activity of mitochondrial CytOx in isolated lymphocytes of patients with iron
      deficiency. Material and methods: A total of 210 cases (2-17 years) were included
      in this prospective study. Serum iron and copper levels were measured. According
      to the serum iron levels, patients were allocated to iron deficient (ID, n = 70)
      and iron deficiency anemia (IDA, n = 70) groups, and iron-sufficient participants
      were allocated to the control group (n = 70). Activity of CytOx in the
      circulating lymphocytes was colorimetrically measured and compared with the
      controls. Results: The CytOx activity was significantly higher in the IDA (2.9 +/
      1.2 mOD/min, n = 62) group compared to the control group (2.4 +/-1.3 mOD/min, n =
      68, p < 0.001). Interestingly, serum copper levels were significantly higher in
      both the ID (106.9 +/-55.5 MUg/dl, n = 64, p = 0.0001) and IDA (115.1 +/-50.2
      MUg/dl, n = 59, p = 0.0001) groups than the control group (72.1 +/-46.7 MUg/dl, n
      = 69). Conclusions: Higher serum copper levels in patients with IDA implicate co
      operative interaction between these trace elements. The elevated CytOx activity
      in patients with IDA is probably secondary to the normal/elevated serum copper
      levels.

PMID- 29379547
TI  - Persistence of primitive reflexes and associated motor problems in healthy
      preschool children.
AB  - Introduction: Retained primitive reflexes can disturb natural development and
      involve difficulties in social and educational children's life. They can also
      impact on psychomotor development. Mature responses in a child's psychomotor
      progress can only occur if the central nervous system itself has reached
      maturity. The process consist the transition made from brain stem reflex response
      to cortically controlled response. This study define the occurrence of primitive
      reflexes in healthy 4-6 years old children and analyze the impact of survived
      primitive reflexes on psychomotor development. Material and methods: The study
      involved 35 participants aged 4-6 years healthy preschool children. The study
      tools were: primitive reflexes tests by Sally Goddard for children and Motor
      Proficiency - Test (MOT 4-6 test) in 18 tasks. Results: Over a half (65%)
      preschool children had survived the primitive reflexes on the residual level.
      Eleven percent of them had no retained primitive reflexes. According to the
      psychomotor ability, 9% of the children were in the category of "altered
      development", 29% in "delayed development", 59% in "normal" and 3% in "very good
      development". The greater the severity of the reflex, the motor efficiency was
      lower (p < 0.05). Conclusions: It seems reasonable to introduce reflexes
      integration therapy in children's with low psychomotor skills. Primitive reflexes
      routinely tested, can contribute to improved early psychomotor development in
      children with needs, thus preventing many difficulties which children can
      encounter within their social and school life.

PMID- 29379548
TI  - The validity of self-reported vs. measured body weight and height and the effect
      of self-perception.
AB  - Introduction: The objective was to assess the validity of self-reported body
      weight and height and the possible influence of self-perception of body mass
      index (BMI) status on the actual BMI during the adolescent period. Material and
      methods: This cross sectional study was conducted on 3918 high school students.
      Accurate BMI perception occurred when the student's self-perception of their BMI
      status did not differ from their actual BMI based on measured height and weight.
      Agreement between the measured and self-reported body height and weight and BMI
      values was determined using the Bland-Altman metod. To determine the effects of
      "a good level of agreement", hierarchical logistic regression models were used.
      Results: Among male students who reported their BMI in the normal region, 2.8%
      were measured as overweight while 0.6% of them were measured as obese. For
      females in the same group, these percentages were 1.3% and 0.4% respectively.
      Among male students who perceived their BMI in the normal region, 8.5% were
      measured as overweight while 0.4% of them were measured as obese. For females
      these percentages were 25.6% and 1.8% respectively. According to logistic
      regression analysis, residence and accurate BMI perception were significantly
      associated with "good agreement" (p <= 0.001). Conclusions: The results of this
      study demonstrated that in determining obesity and overweight statuses, non
      accurate weight perception is a potential risk for students.

PMID- 29379549
TI  - What does the Cantril Ladder measure in adolescence?
AB  - Introduction: The Cantril Scale (CS) is a simple visual scale which makes it
      possible to assess general life satisfaction. The result may depend on the
      health, living, and studying conditions, and quality of social relations. The
      objective of this study is to identify key factors influencing the CS score in
      Polish adolescents. Material and methods: The survey comprised 1,423 parent-child
      pairs (54% girls; age range: 10-17; 67.3% urban inhabitants; 89.4% of parents
      were mothers). Linear and logistic models were estimated; the latter used
      alternative divisions into "satisfied" and "dissatisfied" with life. In addition
      to age and gender, child-reported KIDSCREEN-52 quality of life indexes were taken
      into account, along with some information provided by parents - child physical
      (CSHCN) and mental (SDQ) health, and family socio-economic conditions. Results:
      According to the linear model, nine independent predictors, including six
      dimensions of KIDSCREEN-52, explain 47.2% of the variability of life satisfaction
      on the Cantril Scale. Self-perception was found to have a dominating influence
      (DeltaR2 = 0.301, p < 0.001). Important CS predictors also included Psychological
      Well-being (DeltaR2 = 0.088, p < 0.001) and Parent Relations (DeltaR2 = 0.041, p
      < 0.001). The impact of socioeconomic factors was more visible in boys and in
      older adolescents. According to logistic models, the key factors enhancing the
      chance of higher life satisfaction are Moods and Emotions (cut-off point CS > 5)
      and School Environment (CS > 8 points). None of the models indicated a
      relationship between the CS and physical health. Conclusions: The Cantril Scale
      can be considered a useful measurement tool in a broad approach to psychosocial
      adolescent health.

PMID- 29379550
TI  - How does the activity level of the parents influence their children's activity?
      The contemporary life in a world ruled by electronic devices.
AB  - Introduction: Apart from many positive changes associated with technical
      civilization, there are also - from the health point of view - some threats. The
      reduction in the level of physical activity is one of them. The aim of the study
      was to investigate whether there are any relationships between children's
      physical activity and behaviors, and to assess the impact of the adults' activity
      on their children's habits. Material and methods: The study involved a group of
      340 children aged 7-12 years (mean age: 9.81 +/-1.7) and their parents. In order
      to evaluate children's physical activity and the amount of time that they spend
      with electronic devices, an original questionnaire and the IPAQ questionnaire
      were used. Results: Children usually use electronic devices between 2 and 7 days
      per week (mean: 4.74 +/-0.86), regardless of sex (p > 0.09) and spend between 5
      and 1620 min per week (mean: 459.46 +/-308.1) with their mobile phone, tablet,
      PCs and TVs. 67.92% of boys and 69.61% of girls lead an active lifestyle. The
      children's activity level depends on their parents' level of activity (p <
      0.000001). Parents of semi-active children lead a lifestyle with a moderate level
      of physical activity. Conclusions: The level of physical activity in younger
      children depends on the children's relationship with their parents and their
      level of activity. Children spend a lot of free time with their electronic
      devices. It is necessary to develop and implement activities intended to raise
      awareness of children and their families about the effects of hypokinesis.

PMID- 29379551
TI  - Aerobic and concentration training and allele 7 in the dopamine receptor D4
      (D4DR) gene increase chances of smoking cessation in young Polish women.
AB  - Introduction: One reason for the limited effectiveness of the available smoking
      cessation methods is the fact that the causes of tobacco addiction have not been
      adequately explained yet. Numerous anti-smoking programs aimed at women involve
      intense physical activity. The goal of the study was to evaluate the
      effectiveness of health training for smoking cessation by young women in
      connection with the dopamine receptor gene (D4DR) in their genetic profile.
      Material and methods: Forty-eight adult female smokers were randomly assigned to:
      1) a concentration training group, or 2) an aerobic and concentration training
      group. Genetic and phenotypic data were obtained from 48 participants. Genotyping
      was performed for allele 7 in the D4DR gene. Results: Individuals with allele 7
      in the dopamine receptor D4 gene have two times greater chances (OR = 2.13: 95%
      CI: 0.91-4.96) of quitting smoking than individuals without allele 7. No
      statistical significance was revealed (p = 0.0805). Individuals undertaking
      aerobic training in combination with concentration training are three times more
      likely (OR = 3.06: 95% CI: 1.03-9.05) to quit smoking than individuals who do not
      perform aerobic training (p = 0.0439). Conclusions: The results of the study show
      that an intensive, 6-week health training program had a significant influence on
      smoking cessation. Smoking quitters, who are genetically predisposed and decide
      to take up aerobic training in combination with concentration training, have much
      greater chances of quitting smoking.

PMID- 29379552
TI  - Differential action of polyunsaturated fatty acids and eicosanoids on bleomycin
      induced cytotoxicity to neuroblastoma cells and lymphocytes.
AB  - Introduction: This study was conducted to examine whether bleomycin-induced
      growth inhibitory action on human neuroblastoma cells (IMR-32) is influenced by
      anti-inflammatory metabolites of polyunsaturated fatty acids (PUFAs): lipoxin A4
      (LXA4), resolvin D1 and protectin D1 in vitro. Material and methods: The in vitro
      study was conducted using monolayer cultures of exponentially growing IMR-32
      cells. The effects of various PUFAs and eicosanoids and anti-inflammatory
      metabolites of PUFAs such as lipoxin A4 (LXA4), resolvin D1 and protectin D1 on
      the growth of IMR-32 cells and human lymphocytes in vitro were investigated. The
      potential of PUFAs, eicosanoids and LXA4, resolvin D1 and protectin D1 to modify
      the growth inhibitory effects of bleomycin was also studied in IMR-32 cells and
      human lymphocytes. Results: PUFAs inhibited the growth of IMR-32 cells (EPA > DHA
      = AA > GLA = ALA > DGLA = LA) significantly (p < 0.001) while prostaglandins were
      found to be not effective. Bleomycin-induced growth inhibitory action on IMR-32
      cells was augmented by PUFAs and its metabolites (p < 0.05). PUFAs and LXA4 did
      not inhibit the growth of human lymphocytes and bleomycin-induced growth
      inhibitory action was also not enhanced by these bioactive lipids. Conclusions:
      Bioactive lipids have differential action on normal human lymphocytes and tumor
      cells in vitro. The apparent lack of effect of PUFAs in combination with
      bleomycin on the growth of human lymphocytes in comparison to their growth
      inhibitory action on IMR-32 cells suggests that PUFAs can be used in combination
      with bleomycin to target tumor cells with little concern over this combination's
      effect on the growth of human lymphocytes. Further studies are warranted to
      evaluate these differential effects under in vivo conditions.

PMID- 29379553
TI  - KLF1 gene and borderline hemoglobin A2 in Saudi population.
AB  - Introduction: Elevated HbA2 (hemoglobin A2) level is considered the most reliable
      hematological parameter for the detection of beta-thalassemia carriers. However,
      some carriers are difficult to recognize because the level of HbA2 is not in the
      distinctive carrier range, i.e. 4.0-6.0%; instead, some carriers have HbA2 levels
      between normal and carrier levels, i.e. borderline HbA2 (HbA2 = 3.1-3.9%).
      Studies have shown that variations in the erythroid Kruppel-like factor (KLF1)
      gene lead to borderline HbA2 in beta-thalassemia carriers from various
      populations. The incidence of borderline HbA2 in Saudis is high. Material and
      methods: To confirm the influence of variations in KLF1, HBA1, HBA2 and HBB genes
      for the reduction of the level of HbA2 in Saudi beta-thalassemia carriers, we
      performed a direct sequence analysis of KLF1, HBA1, HBA2 and HBB genes from 212
      healthy Saudis (88 subjects: HbA2 < 3; 72 subjects: HbA2 = 3.1 to 3.9; 52
      subjects HbA2 > 4.3). Results: The presence of the borderline HbA2 level is not
      specific to any type of beta-thalassemia variation or beta+-thalassemia
      variations in Saudis. Two exonic (c.304T>C and c.544T>C) and two 3' untranslated
      region (3'UTR) (c.*296G>A and c.*277C>G) variations have been identified in the
      KLF1 gene for the first time from an Arab population. None of these four
      variations in KLF1 genes are significantly associated with the Saudis with
      borderline HbA2. alpha Globin genotype, -alpha23.7/alpha1alpha2, is found to be
      the most frequent (55.55%) among healthy Saudis with borderline HbA2 compared
      with the other groups (HbA2 < 3 = 20.45%; HbA2 > 4.3 = 13.51%). Conclusions:
      Further studies are necessary to determine the influence of other factors on the
      presence of borderline HbA2 in 41.67% of Saudis.

PMID- 29379554
TI  - Variable clinical presentation of glycogen storage disease type IV: from severe
      hepatosplenomegaly to cardiac insufficiency. Some discrepancies in genetic and
      biochemical abnormalities.

PMID- 29379555
TI  - Propafenone is not effective for severe ventricular arrhythmias in Andersen-Tawil
      syndrome.

PMID- 29379556
TI  - Massive pulmonary embolism in a patient with polysplenia syndrome and interrupted
      inferior vena cava with azygous continuation.

PMID- 29379557
TI  - A pediatric case of rhabdomyolysis with acute renal failure due to co-infection
      with Epstein-Barr virus and Human herpesvirus 6.

PMID- 29379558
TI  - Effect of Whole Exome Sequencing in Diagnosis of Inborn Errors of Metabolism and
      Neurogenetic Disorders.
AB  - Objective: Inborn errors of metabolism are complex disorders with huge
      variability in clinical manifestations. Decreasing cost of whole exome sequencing
      (WES) in recent years, made it affordable. Therefore, we witnessed an increase in
      using WES in diagnosis of genetic diseases, including inherited metabolic
      disorders. Methods: A systematic search was done in well-known databases
      including Medline, Google, Cochrane, and PubMed until 1 Oct 2017. We reviewed the
      articles addressing the use of WES in diagnosis of metabolic and neurogenetic
      diseases to evaluate its impact in diagnosis of these conditions. Results: WES is
      an effective technology with remarkable impact in diagnosis of metabolic and
      neurologic diseases, especially in complex cases. Diagnostic yield of WES for
      these conditions has large variety, ranging from 16% to 68% with an increase
      during recent years. WES can provide fresh valuable information about new
      disease, new variants and phenotypes. Careful analysis and interpretation of data
      obtained by WES and precise evaluation of correlation between clinical
      manifestation and WES findings are necessary to achieve a correct diagnosis.
      Conclusion: WES is effective and useful technology for diagnosis of metabolic and
      neurogenetic diseases, especially in complex or unsolved cases.

PMID- 29379559
TI  - Clinical and Imaging Findings in Childhood Posterior Reversible Encephalopathy
      Syndrome.
AB  - Objective: Posterior reversible encephalopathy syndrome (PRES) is characterized
      by typical radiologic findings in the posterior regions of the cerebral
      hemispheres and cerebellum. The symptoms include headache, nausea, vomiting,
      visual disturbances, focal neurologic deficits, and seizures. The aim of this
      study is to evaluate the clinical and radiological features of PRES in children
      and to emphasize the recognition of atypical features. Materials & Methods: We
      retrospectively examined 23 children with PRES from Mar 2010-Apr 2015 in Inonu
      University Turgut Ozal Medical Center in Turkey. We compared the clinical
      features and cranial MRI findings between underlying diseases of PRES. Results:
      The most common precipitating factors were hypertension (78.2%) and medications,
      namely immunosuppressive and antineoplastic agents (60.8%). Manifestations
      included mental changes (100%), seizures (95.6%), headache (60.8%), and visual
      disturbances (21.7%) of mean 3.6 (range 1-10) days' duration. Cranial magnetic
      resonance imaging (MRI) showed bilateral occipital lesions in all patients,
      associated in 82.6% with less typical distribution of lesions in frontal,
      temporal or parietal lobes, cerebellum, corpus callosum, basal ganglia, thalamus,
      and brain stem. Frontal involvement was predominant, observed in 56.5% of
      patients. Clinical recovery was followed by radiologic resolution in all
      patients. Conclusion: PRES is often unsuspected by the clinician, thus
      radiologists may be the first to suggest this diagnosis on an MRI obtained for
      seizures or encephalopathy. Atypical MRI finding is seen quite often. Rapid
      diagnosis and treatment are required to avoid a devastating outcome.

PMID- 29379560
TI  - Evaluating of Psychiatric Behavior in Obese Children and Adolescents.
AB  - Objective: Obesity is a medical condition that may have a harmful effect on
      health, leading to increased illness and reduced life expectancy. This studyaimed
      to evaluate the relationship of psychiatry disorders in overweight and obese
      children and adolescents. Materials & Methods: In this case-control study, 160
      children and adolescent were enrolled refereed to Clinic of Pediatric
      Endocrinology, Imam Reza hospital, Mashhad, Iran in 2009-2011. The sampling
      method of this study was non-probability and biased. Study instruments were SDQ,
      CDI, STAI, Peds QL. All questionnaires were self-administrating completed by
      subjects or their parents. Differences between groups were examined using t-test
      and chi-square tests as appropriate. Results: There was no significant difference
      on scores of anxiety between two groups. However, significant difference was on
      scores of depression, quality of life, and strength and difficulty between two
      groups. In addition, there was no significant difference in gender effect on
      anxiety and depression. However, emotional symptoms were more in girl. In
      contrast, the conduct problems were more in boys. Anxiety and depression were
      more in adolescents. Conclusion: Obesity has a negative effect on the anxiety,
      depression, and self-esteem of children and adolescents. It might be a more
      important risk factor for depression, anxiety, and other psychiatry disorders.
      This study also emphasizes the importance of prevention of obesity.

PMID- 29379561
TI  - Haplotype Analysis of DXS548 and FRAXAC1 Microsatellite Loci in Iranian Patients
      with Fragile X Syndrome.
AB  - Objective: Fragile X syndrome (FXS) is the most common cause of inherited mental
      retardation caused by expansion of a (CGG) repeat region up to 1000 repeat in 5'
      region of the FMR1 gene located in FRAXA locus Xq27.3. To better understand the
      mechanism involved in expansion of CGG region, the molecular characteristic of
      the flanking microsatellite markers in the region must be clarify in different
      populations. We aimed to examine the potential association between specific
      haplotype and the expanded AC-repeat region in cases and controls chromosomes.
      Materials & Methods: Forty unrelated FXS males and 62 unrelated normal males
      originating from various regions of Iran were haplotyped by analyzing two CA
      repeat markers, FRAXAC1 and DXS548. Results: Significant linkage disequilibrium
      was obtained between DXS548 and FRAXAC1 specific marker alleles and CGG repeat
      expansion among 40 fragile X cases compared to 62 normal controls. The
      frequencies of DXS548 and FRAXAC1 longer alleles in patients were significantly
      higher than that in control group. Two FRAXAC1 long alleles were only observed in
      cases, possibly due to concatenated mutations. The increase of heterozygosities
      in fragile X cases (DXS548 78.6%, FRAXAC1 64.6%) in comparison to the controls
      (DXS548 63.0%, FRAXAC1 47.0%) showed a multimodal distribution of fragile X
      associated alleles. Conclusion: Haplotype analyses with DXS548 and FRAXAC1
      markers represented that haplotype distribution in the normal controls and FXS
      patients were significantly different, representing a weak founder effect.

PMID- 29379562
TI  - A Randomized Clinical Trial Comparing the Efficacy of Melatonin and Amitriptyline
      in Migraine Prophylaxis of Children.
AB  - Objective: The aim of the present research was to compare the effectiveness and
      tolerability of melatonin and amitriptyline in pediatric migraine prevention.
      Materials & Methods: In a parallel single-blinded randomized clinical trial, 5-15
      yr old children with diagnosis of migraine that preventive therapy was indicated
      in whom and were referred to Pediatric Neurology Clinic of Shahid Sadoughi
      Medical Sciences University, Yazd-Iran from 2013-2014, were randomly allocated to
      receive 1 mg/kg amitriptyline or 0.3 mg/kg melatonin for three consecutive
      months. Results: Forty one girls (51.3%) and 39 boys (48.7%) with mean age of
      10.44+/-2.26 yr were evaluated. Good response was seen in 82.5% of amitriptyline
      and 62%.5 of melatonin groups and amitriptyline was statistically significant
      more effective (P=0.04). Severity, duration and Pediatric Migraine Disability
      Assessment score (PedMIDAS) of headache reduced with melatonin from 6.05+/-1.63
      to 4.03+/-1.54 scores, from 2.06+/-1.18 to 1.41+/- 0.41 hours, and from 33.13+/
      9.17 to 23.38+/-9.51 scores, respectively. Severity, duration and PedMIDAS of
      headache decreased with amitriptyline from 6.41+/-1.67to 2.25+/-1.21, from 2.55
      +/-1.85to 0.56+/-0.51h, and from 31.4+/-9.33 to 8.28 +/- 3.75, respectively (All
      P < 0.05). Both drugs were effective in reduction of monthly frequency, severity,
      duration and disability of headache. Daily sleepiness was seen in 7.5% of
      melatonin group as a side effect and adverse events were seen in 22.5% of
      amitriptyline group including daily sleepiness in four, constipation in three and
      fatigue in two children and melatonin was safer than amitriptyline (value =
      0.04). Conclusion: Amitriptyline and melatonin are effective and safe in
      pediatric migraine prophylaxis but amitriptyline can be considered as a more
      effective drug.

PMID- 29379563
TI  - The Relationship of Parental Pain Catastrophizing with Parents Reports of
      Children's Anxiety, Depression, and Headache Severity.
AB  - Objective: Parental pain catastrophizing is a construct recognized to have a
      significant impact on experience of pain in both children and parents. This
      research aimed to investigate the probable relationship of parental pain
      catastrophizing with the parent's reports of children's anxiety, depression and
      headache severity amongst Iranian parents of children with chronic or recurrent
      headache. Materials & Methods: This study was conducted in 2015-16, in two
      pediatric neurological centers located in Tehran, Iran; with a convenience
      sampling method and 212 parents (120 mothers and 92 fathers) of 132 children with
      a chronic or recurrent headache (migraine and tension-type). They completed the
      Pain Catastrophizing Scale; Numeric Pain Rating Scale, asking for the average of
      pain severity in last three months before the research, and the Anxiety and
      Depression subscales of the Children Behavioral Check List. Results: The mean age
      of parents was 35.41 yr (SD=5.58) and the mean age of children was 9.83 yr
      (SD=2.77). A total of 72 girls and 60 boys participated in this study with a mean
      pain severity for headache in last three months before the research of 4.99
      (SD=2.63). Probable sex differences according to parental pain catastrophizing,
      pain severity, anxiety, and depression were assessed amongst parents. In the next
      step, the predictability of pain severity from parental pain catastrophizing was
      evaluated. Results indicated a significant relationship in maternal pain
      catastrophizing and estimates of pain intensity by mothers. Conclusion: These
      findings represent the importance of parent's especially mother's cognitive
      factors affecting their reports of their children's pain and related emotional
      disturbances.

PMID- 29379564
TI  - Factors Influencing the Attendance of Preterm Infants to Neonatal Follow up And
      Early Intervention Services Following Discharge from Neonatal Intensive Care Unit
      during First Year of Life in Iran.
AB  - Objective: The aim of this study was to determine factors influencing the number
      of times neonatal intensive care unit admitted preterm infants attend Neonatal
      Follow up and Early Intervention services (NFEI) during first year of life.
      Materials &Methods: A parent-report questionnaire was administered via phone
      after the first birthday of preterm infants admitted to the NICU at Arash
      Hospital, Tehran, for at least 24 h, and who received standard NICU-based
      therapeutic services, from Apr 2014 to Feb 2015. Data included mother's age,
      education, type of pregnancy, history of abortion or premature birth, self
      reported post-partum depression, number of children, infant's gender, birth
      weight, gestational age, length of stay in the NICU, living area, twin or triplet
      birth, number of siblings, and the child rank. Number of attending times to
      services was recorded. Another question addressed the causes of not attending the
      NFEI services. Results: Ultimately, 119 eligible children participated, 51% were
      girls and whose mean birth weight was 1908+/-626.7 gr, and average length of NICU
      stay was 20.1+/-16.9 d. After multivariate analysis, shorter length of stay in
      the NICU, lower maternal education, number of children, self-declared lack of
      awareness about early intervention services, and self-reported lack of referral
      by a physician were the only factors that continued to be significantly
      correlated, and in fact, the truly influential ones associated with number of
      attending times. Conclusion: This study has defined some predictors of poor
      follow up and early intervention service utilization in a high-risk group of
      infants suggested be addressing and tackling by policymakers.

PMID- 29379565
TI  - Bone Mineral Density and Bone Metabolism in Patients with Duchenne Muscular
      Dystrophy.
AB  - Objective: Poor bone health with related morbidity is a major problem with
      Duchene Muscular Dystrophy (DMD). Decreased mobility and long-term corticosteroid
      therapy are involved in poor bone health in DMD. We investigated bone mineral
      density and bone metabolism in 30 steroid treated DMD patients and also compared
      mentioned factors between ambulated and non-ambulated patients. Materials &
      Methods: In this cross-sectional study, 30 boys (21 patients ambulate and 9 non
      ambulate) with documented DMD, according to genetic analysis, were enrolled in
      2015. Demographic characteristics, neurologic exam findings, muscle function
      score, corticosteroid dose and duration and food frequency questionnaire were
      recorded. Bone mineral density was measured with dual- energy X-ray
      absorptiometry (DEXA) on lumbar spine and left proximal femur. Serum 25
      hydroxyvitamin D, calcium, phosphorus and parathyroid hormone (PTH) levels were
      measured. Results: Osteoporosis was found in 86.7% patients. Mean bone density in
      the lumbar spine was -1.5+/-0.24 and -1.4+/-0.27 in ambulates and non-ambulates
      respectively (P=0.7). Mean bone density at proximal femur was -3.4+/-0.2 in
      ambulates and -3.4+/-0.3 in non-ambulates (P =0.48). Intra-groups statistical
      analysis showed significant difference between bone mineral density at lumbar
      spine and proximal femur in both mentioned groups (P<0.05). Vitamin D deficiency
      was detected in 13 patients (43.3%) and its serum level was significantly lower
      in non-ambulates compared with ambulates. Conclusion: Considering high prevalence
      of vitamin D deficiency and osteoporosis in DMD patients, it seems vitamin D
      supplementation can improve vitamin D status and osteoporosis in these patients,
      especially in non-ambulates.

PMID- 29379566
TI  - Recurrent Stroke in a Child with TRMA Syndrome and SLC19A2 Gene Mutation.
AB  - Here we report a 5-month-old boy with thiamine Responsive Megaloblastic Anemia
      syndrome (TRMA syndrome) with several attacks of stroke, admitted to Mofid
      Children's Hospital, Tehran, Iran, in 2016. In addition to the cardinal clinical
      manifestations of the syndrome, other manifestations comprise thiamine-responsive
      megaloblastic anemia, diabetes mellitus, and sensor neural hearing loss. The
      patient showed the ischemic attack of stroke. Megaloblastic anemia and diabetes
      were diagnosed at 8 months and was successfully treated with vitamin and insulin
      prescription. After treatment of thiamine, diabetes was controlled and insulin
      was discontinued. In spite of the thiamine administration, the second stroke as
      hemorrhagic stroke occurred in the patient after a few months. TRAMA is inherited
      in an autosomal recessive manner. TRMA was confirmed by mutation in SLC19A2. A
      homozygous splice site variant was detected in SLC19A2 gene. Stroke was not
      reported in this syndrome (only in one report about one attack in an adult
      patient) but in this patient, several attacks of stroke were reported before and
      after thiamin administration.

PMID- 29379567
TI  - Rare Presentation of Moyamoya Disease with Sub acute Presentation in Iran.
AB  - Moyamoya disease is a chronic progressive vascular disease of brain characterized
      by bilateral stenosis or occlusion of the arteries around the circle of Willis
      with prominent arterial collateral circulation. We introduce here a patient with
      Moyamoya who was misdiagnosed. She was a 16-yr-old female from north east of Iran
      who complained left hemiparesis and was diagnosed Moyamoya disease by brain and
      cervical CT-Angiography. There was still great difficulty in the diagnosis of
      diffuse white matter lesions. The CT-Angiography showed bilateral internal
      carotid stenosis with "puff of smoke" collateralization arising from the circle
      of Willis, therefore Moyamoya disease was raised. The clinical diagnosis of
      Moyamoya is challenging and misdiagnosis is probable. Therefore, the physicians
      should know this disease and think about it in patients with Juvenile stroke.
      This shows that Moyamoya disease should be considered in differential diagnoses
      especially among young patients presenting with unexplained cerebrovascular
      syndromes.

PMID- 29379568
TI  - Characterization of a de Novo Constitutional Balanced Translocation t
      (2;11)(q33.2;q23.2) with Break Point on the Human NBEAL1-GeneHo.
AB  - Reciprocal balanced translocations associated with clinical features are very
      rare. This study reports cytogenetic and molecular cytogenetic findings in a 3-yr
      old female patient with mild developmental retardation, slight hypotone with a de
      novo balanced 46, XX, t(2; 11) (q33; q23) translocation. Her parent attended
      private office at Tehran, Iran in 2013. G-banded chromosomes and FISH-Analysis
      were used to examine the patient's karyotype as well as her parents. FISH-probes
      prepared with specific RP11-BAC clones mapped near 2q33 and 11q23 regions were
      used to characterize the location of the breakpoints. One of the break points is
      located within the human NBEAL1-Gene locus on chromosome 2, suggesting a
      correlation between this gene disruption and the patient's mild developmental
      retardation.

PMID- 29379569
TI  - Brain Atrophy and Hypomyelination Associated with Iatrogenic Cushing Syndrome in
      an Infant.
AB  - Prolonged use of topical corticosteroids, particularly in infants, albeit rare,
      may lead to Cushing syndrome. Central nervous system abnormalities including
      brain atrophy and delayed myelination on cranial magnetic resonance imaging has
      been reported in patients with corticosteroid treatment. We herein report a 5
      month-old female infant referred to Department of Pediatric Endocrinology,
      Edirne, Turkey with brain atrophy and myelination delay that might be due to
      iatrogenic Cushing syndrome caused by topical corticosteroid use.

PMID- 29379570
TI  - Type 0 Spinal Muscular Atrophy in rare association with congenital Contracture
      and generalized osteopenia.
AB  - Spinal muscular atrophy (SMAs) is a group of rare autosomal recessive diseases in
      which there is degeneration of alpha motor neurons in the spinal cord leading to
      progressive distal motor weakness. Here we report a case of type 0 SMA in a
      female neonate born at the Department of Pediatrics, PGIMS, Rohtak (Haryana)
      India, associated with generalized osteopenia and bony deformity in form of
      unilateral club foot. It may be emphasized that diagnosis of SMA should be kept
      in mind as a differential in cases of unexplained severe generalized hypotonia
      and severe respiratory compromise immediately after birth.

PMID- 29379571
TI  - The Survey of Saliva Compositional Alterations is a Non-invasive Method in
      Determining of Multiple Sclerosis Progression in Children.

PMID- 29379572
TI  - The Role of the Innate Immune System in Oncolytic Virotherapy.
AB  - The complexity of the immune responses is a major challenge in current
      virotherapy. This study incorporates the innate immune response into our basic
      model for virotherapy and investigates how the innate immunity affects the
      outcome of virotherapy. The viral therapeutic dynamics is largely determined by
      the viral burst size, relative innate immune killing rate, and relative innate
      immunity decay rate. The innate immunity may complicate virotherapy in the way of
      creating more equilibria when the viral burst size is not too big, while the
      dynamics is similar to the system without innate immunity when the viral burst
      size is big.

PMID- 29379573
TI  - The Effects of Yoga in Patients Suffering from Subjective Tinnitus.
AB  - Introduction  Tinnitus is a perception of sound in the absence of an external
      source and it is a distressing issue. Yoga is a system of mind-body practices
      with the goal of uniting the body, mind and soul. It has been shown to reduce
      anxiety and stress, as well as improving the quality of life. Objective  The aim
      of this study is to investigate the effects of yoga in patients suffering from
      chronic subjective tinnitus. Methods  Twelve subjects previously diagnosed with
      chronic subjective tinnitus were selected for the study. The patients were asked
      to attend to yoga classes once a week and to practice yoga at home using a
      worksheet for 3 months. Each yoga class consisted of body exercises (asana),
      breathing (pranayama) and meditation (shavasana and yoga nidra). Tinnitus scores
      before and after the yoga classes were compared using the Wilcoxon test. Results 
      Among the 12 patients, there were 4 men and 8 women and their mean age was 52.5
      years. The median duration of tinnitus among the group was 5.4 years. There were
      statistically significant differences in the stress ( p  = 0.01), handicap ( p  =
      0.004) and severity ( p  = 0.007) questionnaires scores. Conclusion  This study
      indicated that yoga practices may reduce life stress and symptoms of subjective
      tinnitus.

PMID- 29379574
TI  - Speech-evoked Brainstem Auditory Responses and Auditory Processing Skills: A
      Correlation in Adults with Hearing Loss.
AB  - Introduction  The auditory system consists of sensory structures and central
      connections. The evaluation of the auditory pathway at a central level can be
      performed through behavioral and electrophysiological tests, because they are
      complementary to each other and provide important information about
      comprehension. Objective  To correlate the findings of speech brainstem-evoked
      response audiometry with the behavioral tests Random Gap Detection Test and
      Masking Level Difference in adults with hearing loss. Methods  All patients were
      submitted to a basic audiological evaluation, to the aforementioned behavioral
      tests, and to an electrophysiological assessment, by means of click-evoked and
      speech-evoked brainstem response audiometry. Results  There were no statistically
      significant values among the electrophysiological test and the behavioral tests.
      However, there was a significant correlation between the V and A waves, as well
      as the D and F waves, of the speech-evoked brainstem response audiometry peaks.
      Such correlations are positive, indicating that the increase of a variable
      implies an increase in another and vice versa. Conclusion  It was possible to
      correlate the findings of the speech-evoked brainstem response audiometry with
      those of the behavioral tests Random Gap Detection and Masking Level Difference.
      However, there was no statistically significant correlation between them. This
      shows that the electrophysiological evaluation does not depend uniquely on the
      behavioral skills of temporal resolution and selective attention.

PMID- 29379575
TI  - From dipivaloylketene to tetraoxaadamantanes.
AB  - Dipivaloylketene (2) is obtained by flash vacuum pyrolysis of furan-2,3-dione 6
      and dimerizes to 1,3-dioxin-4-one 3, which is a stable but reactive ketene. The
      transannular addition and rearrangement of enols formed by the addition of
      nucleophiles to the ketene function in 3 generates axially chiral 2,6,9
      trioxabicyclo[3.3.1]nonadienes (bisdioxines) 4. When arylamines are used as the
      nucleophiles under neutral conditions, decarboxylation occurs during the
      formation of bisdioxines 8. However, when water or alcohols are added to 3 under
      acidic conditions, bisdioxine-carboxylic acids and esters 10 and 11 are obtained.
      Acid hydrolysis of the bisdioxines proceeds through the addition of water to a
      C=C double bond and results in a second transannular oxa-Michael-type reaction
      and generation of tetraoxaadamantanes 5. This reaction is decarboxylative when
      free carboxylic acid functions are present in the bisdioxines, thus forming 21
      and 22, but carboxylic acid derivatives are preserved to yield compounds 20, 23,
      25, 28, and 29. A hydrogenolysis of the dibenzyl ester 23 yields the free
      dicarboxylic acid 24. The tetraoxaadamantanes are formed in high yields (65-95%)
      in most cases, but the addition of water to the concave inside of the bisdioxines
      becomes severely hindered in cyclic derivatives, so that the 38-membered ring
      compound 32 requires microwave heating at 170  degrees C to form
      tetraoxaadamantane 33, and the catenated compound 36 and calix[6]arene derivative
      37 did not form tetraoxaadamantanes. The reaction mechanisms of bisdioxine and
      tetraoxaadamantane formation are discussed.

PMID- 29379576
TI  - Recent applications of click chemistry for the functionalization of gold
      nanoparticles and their conversion to glyco-gold nanoparticles.
AB  - Glycoscience, despite its myriad of challenges, promises to unravel the causes
      of, potential new detection methods for, and novel therapeutic strategies
      against, many disease states. In the last two decades, glyco-gold nanoparticles
      have emerged as one of several potential new tools for glycoscientists. Glyco
      gold nanoparticles consist of the unique structural combination of a gold
      nanoparticle core and an outer-shell comprising multivalent presentation of
      carbohydrates. The combination of the distinctive physicochemical properties of
      the gold core and the biological function/activity of the carbohydrates makes
      glyco-gold nanoparticles a valuable tool in glycoscience. In this review we
      present recent advances made in the use of one type of click chemistry, namely
      the azide-alkyne Huisgen cycloaddition, for the functionalization of gold
      nanoparticles and their conversion to glyco-gold nanoparticles.

PMID- 29379577
TI  - Aminosugar-based immunomodulator lipid A: synthetic approaches.
AB  - The immediate immune response to infection by Gram-negative bacteria depends on
      the structure of a lipopolysaccharide (LPS, also known as endotoxin), a complex
      glycolipid constituting the outer leaflet of the bacterial outer membrane.
      Recognition of picomolar quantities of pathogenic LPS by the germ-line encoded
      Toll-like Receptor 4 (TLR4) complex triggers the intracellular pro-inflammatory
      signaling cascade leading to the expression of cytokines, chemokines,
      prostaglandins and reactive oxygen species which manifest an acute inflammatory
      response to infection. The "endotoxic principle" of LPS resides in its
      amphiphilic membrane-bound fragment glycophospholipid lipid A which directly
      binds to the TLR4.MD-2 receptor complex. The lipid A content of LPS comprises a
      complex mixture of structural homologs varying in the acylation pattern, the
      length of the (R)-3-hydroxyacyl- and (R)-3-acyloxyacyl long-chain residues and in
      the phosphorylation status of the beta(1->6)-linked diglucosamine backbone. The
      structural heterogeneity of the lipid A isolates obtained from bacterial cultures
      as well as possible contamination with other pro-inflammatory bacterial
      components makes it difficult to obtain unambiguous immunobiological data
      correlating specific structural features of lipid A with its endotoxic activity.
      Advanced understanding of the therapeutic significance of the TLR4-mediated
      modulation of the innate immune signaling and the central role of lipid A in the
      recognition of LPS by the innate immune system has led to a demand for well
      defined materials for biological studies. Since effective synthetic chemistry is
      a prerequisite for the availability of homogeneous structurally distinct lipid A,
      the development of divergent and reproducible approaches for the synthesis of
      various types of lipid A has become a subject of considerable importance. This
      review focuses on recent advances in synthetic methodologies toward LPS
      substructures comprising lipid A and describes the synthesis and immunobiological
      properties of representative lipid A variants corresponding to different
      bacterial species. The main criteria for the choice of orthogonal protecting
      groups for hydroxyl and amino functions of synthetically assembled beta(1->6)
      linked diglucosamine backbone of lipid A which allows for a stepwise introduction
      of multiple functional groups into the molecule are discussed. Thorough
      consideration is also given to the synthesis of 1,1'-glycosyl phosphodiesters
      comprising partial structures of 4-amino-4-deoxy-beta-L-arabinose modified
      Burkholderia lipid A and galactosamine-modified Francisella lipid A. Particular
      emphasis is put on the stereoselective construction of binary glycosyl
      phosphodiester fragments connecting the anomeric centers of two aminosugars as
      well as on the advanced P(III)-phosphorus chemistry behind the assembly of
      zwitterionic double glycosyl phosphodiesters.

PMID- 29379578
TI  - Photocatalytic formation of carbon-sulfur bonds.
AB  - This review summarizes recent developments in photocatalyzed carbon-sulfur bond
      formation. General concepts, synthetic strategies and the substrate scope of
      reactions yielding thiols, disulfides, sulfoxides, sulfones and other
      organosulfur compounds are discussed together with the proposed mechanistic
      pathways.

PMID- 29379579
TI  - Petascale supercomputing to accelerate the design of high-temperature alloys.
AB  - Recent progress in high-performance computing and data informatics has opened up
      numerous opportunities to aid the design of advanced materials. Herein, we
      demonstrate a computational workflow that includes rapid population of high
      fidelity materials datasets via petascale computing and subsequent analyses with
      modern data science techniques. We use a first-principles approach based on
      density functional theory to derive the segregation energies of 34 microalloying
      elements at the coherent and semi-coherent interfaces between the aluminium
      matrix and the theta'-Al2Cu precipitate, which requires several hundred supercell
      calculations. We also perform extensive correlation analyses to identify
      materials descriptors that affect the segregation behaviour of solutes at the
      interfaces. Finally, we show an example of leveraging machine learning techniques
      to predict segregation energies without performing computationally expensive
      physics-based simulations. The approach demonstrated in the present work can be
      applied to any high-temperature alloy system for which key materials data can be
      obtained using high-performance computing.

PMID- 29379580
TI  - Errata to "Associations among anthropometric measures, food consumption, and
      quality of life in school-age children in Tanzania"[J Rural Med 12(1): 38-45].
AB  - [This corrects the article on p. 38 in vol. 12, PMID: 28593016.].

PMID- 29379581
TI  - Erratum to "Infant with nasolacrimal sinonasal myxoma: Diffusion MRI features"
      [Radiology Case Reports 2015;10: article 1104].
AB  - [This corrects the article DOI: 10.2484/rcr.v10i2.1104.].

PMID- 29379582
TI  - Characterization of Surface Modification of 347 Stainless Steel upon Shot
      Peening.
AB  - Plastic deformations, such as those obtained by shot peening on specimen surface,
      are an efficient way to improve the mechanical behavior of metals. Generally,
      scanning electron microscopy (SEM) and electron backscattered diffraction (EBSD)
      are commonly used to observe the complex microstructural evolutions, such as
      grain refinement and phase transformation, induced by the surface treatment. In
      this work, the microstructure of 347 stainless steel, after ultrasonic shot
      peening (USP) treatments, was investigated. SEM, EBSD, transmission electron
      microscopy, and X-ray diffraction were used to observe the microstructural
      evolutions, such as grain refinement and phase transformation. Deformation depth
      after the USP treatment was about 200 MUm. Grain size on the treated surface
      layer was about 100 nm, with two phases: austenite and alpha'-martensite. The
      percentages of the austenite and alpha'-martensite phases were 54% and 46%,
      respectively, which constitute an exact expression of the degree of plastic
      deformation on austenitic stainless steel.

PMID- 29379584
TI  - Low-Level Laser Irradiation Exerts Antiaggregative Effect on Human Platelets
      Independently on the Nitric Oxide Metabolism and Release of Platelet Activation
      Markers.
AB  - Aim: The goal of the study is to develop a model allowing to investigate
      precisely the effect of low-level laser therapy (LLLT) on platelet aggregation
      and to verify the hypothesis regarding the role of the nitric oxide (NO)
      bioavailability and platelet activation markers in modulating platelet
      aggregation. Methods: A total of 41 healthy volunteers at the age of 21-45 years
      were investigated. At first, platelet aggregation in response to three agonists
      (TRAP, ADP, and collagen) was evaluated following previous exposure to different
      doses of laser radiation (lambda = 662 nm) to assess the dose-response effect.
      Subsequently, plasma levels of platelet activation markers (PF4-platelet factor-4
      and sP-selectin) as well as the substrate for nitric oxide synthase, L-arginine,
      and its competitive inhibitors (ADMA-asymmetric dimethylarginine and SDMA
      symmetric dimethylarginine) were measured. Results: All doses of laser
      irradiation significantly reduced the aggregation. However, the most pronounced
      effect was observed for 19.7 J/cm2. No significant differences in the levels of
      platelet activation markers nor in the nitric-oxide-metabolic-pathway compounds
      between analyzed groups were noted. Conclusions: We have demonstrated in the
      established in vitro experimental model that the LLLT in a reproducible manner
      decreases the whole blood platelet aggregation regardless of the NO
      bioavailability or changes in the platelet activation markers.

PMID- 29379583
TI  - Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases.
AB  - GSK-3 is a ubiquitously expressed serine/threonine kinase existing as GSK-3alpha
      and GSK-3beta isoforms, both active under basal conditions and inactivated upon
      phosphorylation by different upstream kinases. Initially discovered as a
      regulator of glycogen synthesis, GSK-3 is also involved in several signaling
      pathways controlling many different key functions. Here, we discuss recent
      advances regarding (i) GSK-3 structure, function, regulation, and involvement in
      several cancers, including hepatocarcinoma, cholangiocarcinoma, breast cancer,
      prostate cancer, leukemia, and melanoma (active GSK-3 has been shown to induce
      apoptosis in some cases or inhibit apoptosis in other cases and to induce cancer
      progression or inhibit tumor cell proliferation, suggesting that different GSK-3
      modulators may address different specific targets); (ii) GSK-3 involvement in
      autophagy modulation, reviewing signaling pathways involved in neurodegenerative
      and liver diseases; (iii) GSK-3 role in oxidative stress and autophagic cell
      death, focusing on liver injury; (iv) GSK-3 as a possible therapeutic target of
      natural substances and synthetic inhibitors in many diseases; and (v) GSK-3 role
      as modulator of mammalian aging, related to metabolic alterations characterizing
      senescent cells and age-related diseases. Studies summarized here underline the
      GSK-3 multifaceted role and indicate such kinase as a molecular target in
      different pathologies, including diseases associated with autophagy
      dysregulation.

PMID- 29379585
TI  - Cadmium-Induced Oxidative Stress Impairs Glycemic Control in Adolescents.
AB  - Experimental evidence suggests that cadmium (Cd) boosts oxidative stress that may
      result in toxicity on the endocrine system also in humans. The aim of this study
      was to investigate the glycemic control and oxidative stress markers in male
      adolescents with increased urinary levels of cadmium. We investigated 111 males,
      aged 12-14 years, living in a polluted area of Sicily and a control age-matched
      population (n = 60) living 28-45 km far from the polluted site. Malondialdehyde
      (MDA), total antioxidant activity (TAC), metallothionein-1A (MT-1A) gene
      expression, insulin resistance by the homeostatic model assessment (HOMA-IR), and
      urinary cadmium were investigated. Cd levels were significantly higher in
      adolescents living in the polluted area than in control age-matched subjects.
      Adolescents with elevated Cd levels had a significant increase in MDA, MT-1A, and
      HOMA-IR and reduced TAC compared to the control group. A robust correlation was
      found between urinary cadmium and MT-1A, HOMA-IR, and MDA whereas an inverse
      correlation was identified between urinary cadmium and TAC. This study indicates
      that cadmium burden alters glycemic control in adolescents and suggests that
      oxidative stress plays a key role in cadmium-induced insulin resistance,
      increasing the risk of developing metabolic disorders.

PMID- 29379586
TI  - Impaired Oxidative Status Is Strongly Associated with Cardiovascular Risk
      Factors.
AB  - The main target of primary prevention is the identification of cardiovascular
      risk factors aimed at reducing of the adverse impact of modifiable factors, such
      as lifestyle and pharmacological treatments. In humans, an alteration of the
      oxidative status has been associated with several pathologies, including diabetes
      and cardiovascular diseases. However, the prognostic relevance of circulating
      oxidative stress biomarkers remains poorly understood. Our study explored, in a
      healthy population (n = 322), the relationship between oxidative status and
      cardiovascular risk factors. Here, we were successful in demonstrating that
      plasmatic oxidative status is significantly associated with traditional
      cardiovascular risk factors. We revealed a significant depletion in the efficacy
      of total plasma antioxidant barrier in high cardiovascular risk categories, and
      we confirmed an age-related alteration of oxidative status. The efficacy of total
      plasma antioxidant barrier is significantly depleted in relation to metabolic
      disorders. Interestingly, the cholesterol imbalance is the main factor in
      depleting the efficacy of total plasma antioxidant barrier. The oxidative status
      is also influenced by hypertension, and a slight increase in systolic blood
      pressure determines a highly significant effect. We showed that the first
      detectable event of a redox disturbance is the repairing intervention of the
      antioxidant barrier that is thus decreased as overutilized.

PMID- 29379587
TI  - Does posttraumatic stress predict frequency of general practitioner visits in
      parents of terrorism survivors? A longitudinal study.
AB  - Background: Life threat to children may induce severe posttraumatic stress
      reactions (PTSR) in parents. Troubled mothers and fathers may turn to their
      general practitioner (GP) for help. Objective: This study investigated frequency
      of GP visits in mothers and fathers of adolescent and young adult terrorism
      survivors related to their own PTSR and PTSR in their surviving children. Method:
      Self-reported early PTSR (4-5 months post-disaster) in 196 mothers, 113 fathers
      and 240 survivors of the 2011 Utoya terrorist attack were linked to parents'
      three years pre- and post-disaster primary healthcare data from a national
      reimbursement claims database. Frequency of parents' GP visits was regressed on
      parent and child PTSR, first separately, then in combination, and finally by
      including an interaction. Negative binominal regressions, adjusted for parents'
      pre-disaster GP visits and socio-demography, were performed separately for
      mothers and fathers and for the early (<6 months) and delayed (6-36 months)
      aftermath of the terrorist attack. Results: Parents' early PTSR were
      significantly associated with higher early frequency of GP visits in mothers
      (rate ratio, RR = 1.31, 95%CI 1.09-1.56) and fathers (RR = 1.40, 95%CI 1.03
      1.91). In the delayed aftermath, early PTSR were significantly associated with
      higher frequency of GP visits in mothers only (RR = 1.21, 95%CI 1.04-1.41). Early
      PTSR in children were not significantly associated with an overall increase in GP
      visits. On the contrary, in mothers, child PTSR predicted significant decrease in
      GP visits the delayed aftermath (RR = 0.83, 95%CI 0.71-0.97). Conclusions: Our
      study suggests that GPs may play an important role in identifying and providing
      for parents' post-disaster healthcare needs. GPs need to be aware that distressed
      individuals are likely to approach them following disasters and must prepare for
      both short- and long-term healthcare needs.

PMID- 29379589
TI  - Economic burden made celiac disease an expensive and challenging condition for
      Iranian patients.
AB  - Aim: The aim of this study was to estimate the economic burden of celiac disease
      (CD) in Iran. Background: The assessment of burden of CD has become an important
      primary or secondary outcome measure in clinical and epidemiologic studies.
      Methods: Information regarding medical costs and gluten free diet (GFD) costs
      were gathered using questionnaire and checklists offered to the selected patients
      with CD. The data included the direct medical cost (including Doctor Visit,
      hospitalization, clinical test examinations, endoscopies, etc.), GFD cost and
      loss productivity cost (as the indirect cost) for CD patient were estimated. The
      factors used for cost estimation included frequency of health resource
      utilization and gluten free diet basket. Purchasing Power Parity Dollar (PPP$)
      was used in order to make inter-country comparisons. Results: Total of 213 celiac
      patients entered to this study. The mean (standard deviation) of total cost per
      patient per year was 3377 (1853) PPP$. This total cost including direct medical
      cost, GFD costs and loss productivity cost per patients per year. Also the mean
      and standard deviation of medical cost and GFD cost were 195 (128) PPP$ and 932
      (734) PPP$ respectively. The total costs of CD were significantly higher for
      male. Also GFD cost and total cost were higher for unmarried patients.
      Conclusion: In conclusion, our estimation of CD economic burden is indicating
      that CD patients face substantial expense that might not be affordable for a good
      number of these patients. The estimated economic burden may put these patients at
      high risk for dietary neglect resulting in increasing the risk of long term
      complications.

PMID- 29379588
TI  - Systematic review of pancreatic cancer epidemiology in Asia-Pacific Region: major
      patterns in GLOBACON 2012.
AB  - Pancreatic cancer is one of the deadliest cancers with short-term survival rates.
      Trends for pancreatic cancer incidence and mortality varied considerably in the
      world. To date, the causes of pancreatic cancer are not known sufficiently,
      although certain risk factors have been identified such as, smoking, obesity,
      life style, diabetes mellitus, alcohol, dietary factors and chronic pancreatitis.
      Since there are no current screening recommendations for pancreatic cancer,
      primary prevention is very important. Therefore, up-to-date statistics on
      pancreatic cancer occurrence and outcome are essential for the primary prevention
      of this disease. Due to the lack of information on epidemiology of pancreatic
      cancer in most Asian countries, and limited of statistics and registration system
      in this area, we conducted a systematic review study to evaluate the most recent
      data concerning epidemiology of pancreatic cancer in Asia-Pacific region. In this
      review we focused on collected recent data on incidence, mortality, survival and
      risk factors of pancreatic cancer in this region. In addition, we reviewed and
      used the data of GLOBOCAN 2012 in this paper to complete the information as a
      source of compiling pancreatic cancer incidence and mortality rate.

PMID- 29379590
TI  - The effect of telenursing on self-efficacy in patients with non-alcoholic fatty
      liver disease: a randomized controlled clinical trial.
AB  - Aim: This study aimed to assess the effect of telenursing on nutritional behavior
      and physical activity self-efficacy in patients with non-alcoholic fatty liver
      disease (NAFLD). Background: NAFLD is the most common liver disorder, which has a
      chronic course. Therefore, routine monitoring of these patients by medical staff
      helps them actively participate in the healing process and promote their self
      efficacy. Methods: In this randomized controlled clinical trial, 60 patients were
      chosen through convenience sampling among patients with NAFLD. After obtaining
      written informed consents, the participants were randomly divided into an
      intervention and a control group (each containing 30 subjects). The participants
      received diet consultation individually and were taught how to perform physical
      activities. Telephone intervention was conducted in the intervention group for 12
      weeks. The study questionnaires were completed by the participants before and
      after the intervention. The data were analyzed using the SPSS statistical
      software. Results: Based on the results, the mean score of nutritional behavior
      and physical activity self-efficacy increased in the study groups after the
      intervention. This increase was statistically significant only in the
      intervention group. Additionally, the two groups were significantly different
      regarding the mean scores of nutritional behavior and physical activity self
      efficacy. Conclusion: Telenursing could improve self-efficacy and physical
      activity in patients with NAFLD.

PMID- 29379591
TI  - Analysis of TLR7, SOCS1 and ISG15 immune genes expression in the peripheral blood
      of responder and non-responder patients with chronic Hepatitis C.
AB  - Aim: To evaluate the baseline expression of the immune genes in PBMCs of
      responder and non-responder patients with chronic Hepatitis C. Background:
      Although the contribution of peripheral blood mononuclear cell (PBMC) gene
      expression in treatment outcome of hepatitis C virus (HCV) infection is supposed,
      it has remained to be distinctly delineated. The baseline expression of the
      immune genes inside PBMCs may reflect the responsiveness status following IFN
      treatment. Methods: Totally, 22 chronic HCV encompasses 10 responders and 12 non
      responsive cases enrolled randomly regarding medical records. The PBMCs from the
      peripheral blood samples were isolated and then incubated for 6 hours in the
      culture media. The baseline expression of TLR7, SOCS1 and ISG15 was measured by
      Real time PCR. Results: The gene expression pattern in PBMCs of both groups
      showed a similar trend. The expression of SOCS1 and TLR7 genes showed higher
      levels in non-responder group (P>0.05). The result of ISG15 showed a higher but
      non-significant expression in the responder group (P>0.05). Conclusion: The
      similar pattern of TLR7, SOCS1 and ISG15 expression in the responder and non
      responder patients indicated their poor discriminating and predictive value in
      PBMCs sample.

PMID- 29379592
TI  - The relationship between expression of Toll-like receptor 4 in chronic hepatitis
      C patients and different stages of liver fibrosis.
AB  - Aim: The objective of this work is to find out whether there is a relation
      between the expression of TLR4 and fibrosis progression in chronic HCV patients.
      Background: Toll-like Receptor 4 (TLR4) is a pattern recognition receptor whose
      activation results in the production of several pro-inflammatory cytokines.
      Methods: Fifty patients with chronic HCV were included. They were divided into
      group A: 40 patients (F1-F4) and group B (control group) which included ten
      patients (F0) based on fibroscan value. All patients were exposed to clinical and
      laboratory evaluations preliminary to antiviral therapy, assessment of TLR4 mRNA
      by Real Time- PCR. Results: Twenty-eight males and 22 females with a mean age
      28.9+/-6.1 years. The mean TLR4 expression is 11.2+/-7.4 folds, TLR4 expression
      in F0 group is 2.8+/-1.9, in F1 group 4.8+/-1.5, F2 group 10.2+/-2.5, F3 group
      16.8+/-1.5 and in F4 21.3+/-3.6 folds (p<0.001). TLR4 showed a positive
      correlation with age, fibrosis stage, HCV RNA, serum transaminases, total
      bilirubin and prothrombin time, a negative correlation with platelet count and
      serum albumin. Fibrosis progression was independently associated with TLR4
      expression (beta=0. 648, P<0.0001), RNA (beta= 0.160, P =0.001) and platelet
      count (beta= -0.248, P = 0.004). Conclusion: The expression of TLR4 is highly
      correlated with the fibrosis progression; TLR4 may be a potential target for
      drugs to limit the progression of fibrosis.

PMID- 29379593
TI  - Association of the epidermal growth factor gene +61A>G polymorphism with
      hepatocellular carcinoma in an Iranian population.
AB  - Aim: The aim of this study was to address the association of the EGF gene +61A/G
      polymorphisms and HCC susceptibility in an Iranian population. Background: The
      association of epidermal growth factor (EGF) gene +61A/G polymorphism (rs4444903)
      and hepatocellular carcinoma (HCC) has been investigated in several populations.
      However, the findings are controversial. Methods: A total of 40 unrelated HCC
      patients and 106 healthy individuals were enrolled in this study. Genomic DNA of
      HCC patients was extracted from formalin-fixed, paraffin-embedded samples using
      CinnaPure DNA kit according to manufacturer's instructions. Genomic DNA of
      healthy individuals, also, was extracted from peripheral blood cells using the
      boiling method. The rs4444903 (A/G) polymorphism was genotyped using the
      polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)
      method. Results: Significant association was found for the EGF +61A allele and
      HCC risk [OR = 1.72, 95% CI (1.02 - 2.90), P value = 0.04]. Also, significant
      association was observed for the EGF +61A/G genotypes and HCC risk under
      codominant and dominant models by SNPStats software analysis. Conclusion: Our
      findings suggest that the EGF gene +61A/G polymorphism (rs4444903) might be a
      risk factor for susceptibility to HCC in Iranian population. However, further
      studies using more samples are needed.

PMID- 29379594
TI  - Reliability and validity of the Persian version of patient assessment of
      constipation- quality of life (PAC-QOL) questionnaire.
AB  - Aim: The present study aimed to assess the reliability and validity of Persian
      version of patient assessment of constipation: quality of life (PAC-QOL)
      questionnaire in Iranian patients. Background: Chronic constipation has
      significant effects on daily living, wellbeing and individuals' quality of life
      (QOL). Validated tools can help us to assessing QOL in affected ones and
      facilitating clinical management of them. Methods: The English version of Patient
      Assessment of Constipation: Quality of Life (PAC-QOL) was translated into the
      Persian language and was confirmed by back-translation. One hundred and forty
      patients with functional constipation, according Rome III criteria, completed the
      questionnaires .The questionnaires were analyzed using Cronbach's Alpha internal
      consistency score to determine the reliability. Twenty medical experts were then
      asked to evaluate the PAC-QOL and the results were used to calculate the Content
      Validity Ratio (CVR) and Content Validity Index (CVI). Results: Due to obtained
      value for Cronbach's alpha (0.975) and also for the subscale of physical
      discomfort (0.930), psychosocial discomfort (0.975) and worries and concerns
      (0.915), the internal consistency is established. According to medical experts'
      opinions, the value of CVR ranged from 0.5 to 0.8 and the value of CVI was 0.81.
      Conclusion: The Persian version of PAC-QOL questionnaire is shown to have
      acceptable reliability and validity to be used for psychometric evaluation in
      Iranian patients complaining of functional constipation.

PMID- 29379595
TI  - Network analysis of common genes related to esophageal, gastric, and colon
      cancers.
AB  - Aim: The aim of this study was to provide a biomarker panel for esophageal,
      gastric and colorectal cancers. It can help introducing some diagnostic
      biomarkers for these diseases. Background: Gastrointestinal cancers (GICs)
      including esophageal, gastric and colorectal cancers are the most common cancers
      in the world which are usually diagnosed in the final stages and due to
      heterogeneity of these diseases, the treatments usually are not successful. For
      this reason, many studies have been conducted to discover predictive biomarkers.
      Methods: In the present study, 507 genes related to esophageal, gastric and colon
      cancers were extracted.. The network was constructed by Cytoscape software
      (version 3.4.0). Then a main component of the network was analyzed considering
      centrality parameters including degree, betweenness, closeness and stress. Three
      clusters of the protein network accompanied with their seed nodes were determined
      by MCODE application in Cytoscape software. Furthermore, Gene Ontology (GO)
      analysis of the key genes in combination to the seed nodes was performed.
      Results: The network of 17 common differential expressed genes in three
      esophageal, gastric and colon adenocarcinomas including 1730 nodes and 9188 edges
      were constructed. Eight crucial genes were determined. Three Clusters of the
      network were analyzed by GO analysis. Conclusion: The analyses of common genes of
      the three cancers showed that there are some common crucial genes including TP53,
      EGFR, MYC, AKT1, CDKN2A, CCND1 and HSP90AA1 which are tightly related to
      gastrointestinal cancers and can be predictive biomarkers for these cancers.

PMID- 29379596
TI  - Celiac disease and hepatitis C relationships in transcriptional regulatory
      networks.
AB  - Aim: we mainly aimed to elucidate potential comorbidities between celiac disease
      and hepatitis c by means of data and network analysis approaches. Background:
      understanding the association among the disorders evidently has important impact
      on the diagnosis and therapeutic approaches. Celiac disease is the most
      challenging, common types of autoimmune disorders. On the other hand, hepatitis c
      virus genome products like some proteins are supposed to be resemble to gliadin
      types that in turn activates gluten intolerance in people with inclined to gluten
      susceptibilities. Moreover, a firm support of association between chronic
      hepatitis and celiac disease remains largely unclear. Henceforth exploring cross
      talk among these diseases will apparently lead to the promising discoveries
      concerning important genes and regulators. Methods: 321 and 1032 genes associated
      with celiac disease and hepatitis c retrieved from DisGeNET were subjected to
      build a gene regulatory network. Afterward a network-driven integrative analysis
      was performed to exploring prognosticates genes and related pathways. Results:
      105 common genes between these diseases included 11 transcription factors were
      identified as hallmark molecules where by further screening enriched in
      biological GO terms and pathways chiefly in immune systems and signaling pathways
      such as chemokines, cytokines and interleukins. Conclusion: in silico data
      analysis approaches indicated that the identified selected combinations of genes
      covered a wide range of known functions triggering the inflammation implicated in
      these diseases.

PMID- 29379597
TI  - Cryptosporidium species subtypes and associated clinical manifestations in Indian
      patients.
AB  - Aim: Present hospital based study was carried out at our tertiary care centre
      with an aim to study the distribution of Cryptosporidium species subtypes in
      patients with complaints of diarrhea. Background: Cryptosporidium species are one
      of the important causative agents of parasitic diarrhea, amongst which
      Cryptosporidium hominis (C.hominis) and Cryptosporidium parvum (C.parvum) are the
      two major species that are associated with human cryptosporidiosis. Methods: Four
      hundred and fifty (n=450) diarrheic patients complaining of different types of
      diarrhea were enrolled in the present study. Both microscopic and molecular
      diagnostic methods were used for the detection as well as for identification of
      Cryptosporidium species and its speciation and subtyping. Results: Forty one
      (n=41) and forty three (n=43) patients were positive for Cryptosporidium species
      by microscopy and Polymerase chain reaction (PCR) assay respectively. Of these 43
      cases, 70% (30/43) were identified as C. hominis and 21% (9/43) was as C. parvum,
      7% (3/43) was as Cryptosporidium felis (C.felis) and 2% (1/43) as Cryptopsoridium
      viatorum (C. viatorum) respectively . Upon subtyping of C. hominis and C. parvum,
      16 subtypes belonging to 8 different subtype families could be identified. The
      frequency of different families were Ia (13%, 5/39), Ib (15%, 6/39), Id (18%,
      7/39), Ie (30%, 12/39) and IIa (5%, 2/39), IIc (8%, 3/39), IId (8%, 3/39) and IIe
      (3%, 1/39). Conclusion: Our study results strongly suggest and reinforces the
      fact that most of the human cryptosporidiosis is anthroponotic and we expect that
      present molecular epidemiological data will provide more insight to unravel the
      changing clinical paradigm of human cryptosporidiosis at large.

PMID- 29379598
TI  - Molecular characterization of Shigella spp. isolates from a pediatric hospital in
      Southwestern Iran.
AB  - Aim: In This study focused on the detection of dominant clones and genetic
      relationship of Shigella spp. isolated from children with diarrhea in the main
      pediatric hospital in Ahvaz by multi-locus sequence typing (MLST) technique.
      Background: Shigellosis is considered as one of the problematic bacterial
      infections for public health in the world. Khuzestan province in the Southwestern
      part of Iran is a known endemic area for infections due to Shigella. There are
      limited molecular epidemiological data for Shigella spp. in this area. Methods: A
      total of 50 Shigella spp. were isolated from January-June 2015 based on
      conventional microbiology and serology tests. The Sequence types (ST) of Shigella
      isolates which are characterized by Enterobacterial repetitive intergenic
      consensus (ERIC-PCR) were detected by MLST technique. Results: Among 50 Shigella
      isolates, a total of 31(62%), 16(32%) and 3 (6%) of Shigella isolates were
      identified as S. flexneri, S.sonneii, and S.boydii, respectively. Two different
      sequence types (ST152 and ST245) were identified in Shigella isolates. ST152 was
      detected in S.sonnei and ST245 in S. flexneri and S. boydii isolates. Conclusion:
      Based on MLST data, the stable and genetically linked Shigella clones are the
      cause of Shigella infections in children in Southwestern Iran.

PMID- 29379599
TI  - Development of PBC/SSc overlap syndrome in chronic GVHD patient: immunological
      implications in the presence of mitochondrial, nucleolar and spindle midzone
      autoantigens.
AB  - Chronic Graft versus Host Disease (cGVHD) is a complex disease resulting from
      donor T-cell recognition of a genetically disparate recipient that is unable to
      reject donor cells after allogeneic Stem Cell Transplantation (HSCT). cGVHD has
      some features resembling to autoimmune diseases (AD) such as Sjogren syndrome,
      primary biliary cirrhosis (PBC) and scleroderma (SSc). Also patients with cGVHD
      could develop extensive cGVHD with scleroderma-like skin manifestations and other
      clinical signs similar to those of patients with scleroderma. We take into
      consideration a patient with GVHD that developed PBC/SSc overlap syndrome with a
      complex and particular autoantibodies profile. Indirect immunofluorescence (IIF)
      with double coloration showed a cytoplasmic mitochondrial-like pattern, a clumpy
      nucleolar staining pattern, and a cell-cycle related staining pattern. Following
      anaphase onset, proteins regulator of cytokinesis localizes to the overlap zone
      on the ends of midzone microtubules and becomes compacted during furrow
      ingression to form the midbody. Second level tests confirmed the presence of anti
      mitochondrial antibodies M2-subunit but no other autoantibodies were found. We
      performed a home-made immunoblot analysis that identified a 37 kDa fibrillarin
      band, and not identify 47 kDa, 31KDa and 18/20 kDa bands. After literature review
      of these possible cellular localizations, the proteins recognized by our
      patient's serum seem likely to be Aab to core midzone organizer components.
      However, due to the unavailability of the proper techniques in our laboratory, we
      were not able to further characterize them. The pathogenesis and morbidity of
      cGVHD after HSCT remains enigmatic, but the presence of specific autoantibodies
      are the hallmark of AD and represent a possibility of differential diagnosis.
      Standard techniques combined with the use of non-routinely laboratory techniques
      are a usefully and complementary method for studying difficult and particular
      cases. In fact, these autoantibodies will be considered as ''diagnostic'' and not
      as ''esoteric'' antibodies. In conclusion, a re-assessment of the diagnostic
      protocols in cGVHD together with a precise observation of the clinical and
      laboratory picture will ultimately help us clarify the disease and could provide
      a better understanding of the immune network deregulation.

PMID- 29379600
TI  - PAX-5 positive anaplastic large cell lymphoma presenting by dysphagia; a case
      report.
AB  - Anaplastic large cell lymphoma (ALCL) is a distinct pathologic entity with
      characteristic morphologic, im!munophenotypic and cytogenetic features.
      Obstructive symptoms are rare presentation of ALCL. We report a 16-year-old boy
      who initially presented with dysphagia. Upper gastrointestinal endoscopy revealed
      severe stenosis with an infiltrative process starting from 24 cm of incisors in
      lower esophagus Esophageal mucosal biopsy demonstrated lymphomatous involvement
      that ancillary tests confirmed the diagnosis of ALCL, ALK (kinase-positive), and
      PAX5 positive. The patient responded to CHOP-based chemotherapy. This case
      illustrated an unusual presentation of primary Non Hodgkin lymphoma of esophagus.

PMID- 29379601
TI  - Recent advances in inflammatory bowel disease.

PMID- 29379602
TI  - Prealamethicin F50 and related peptaibols from Trichoderma arundinaceum:
      Validation of their authenticity via in situ chemical analysis.
AB  - In the field of natural products chemistry, a common question pertains to the
      authenticity of an isolated compound, i.e. are the interesting side chains
      biosynthesized naturally or an artefact of the isolation/purification processes?
      The droplet-liquid microjunction-surface sampling probe (droplet-LMJ-SSP) coupled
      to a hyphenated system (UPLC-UV-HRESIMS) empowers the analysis of natural product
      sources in situ, providing data on the biosynthetic timing and spatial
      distribution of secondary metabolites. In this study the droplet-LMJ-SSP was
      utilized to validate the authenticity of two new peptaibols (2 and 3) as
      biosynthesized secondary metabolites, even though both them had structural
      features that could be perceived as artefacts. Compounds 2 and 3 were isolated
      from the scaled up fermentation of Trichoderma arundinaceum (strain MSX70741),
      along with a new member of the trichobrevin BIII complex (1), and four known
      compounds (4-7). The structures of the isolates were established using a set of
      spectroscopic and spectrometric methods, and their absolute configurations were
      determined by Marfey's analysis. The cytotoxic activity of compounds 1, 3, 4 and
      6 was evaluated against a panel of cancer cell lines, where cytotoxic activity in
      the single digit MUM range was observed.

PMID- 29379603
TI  - 'Massilimalia timonensis' sp. nov., a new bacterium species isolated from human
      faeces after decontamination with alcohol.
AB  - We describe the main characteristics of a new bacterial species 'Massilimalia
      timonensis' sp. nov. The type strain Marseille-P3753T (=CSUR P3753) was isolated
      from the stool of a healthy Senegalese man.

PMID- 29379604
TI  - Typing of staphylococcal cassette chromosome mec encoding methicillin resistance
      in Staphylococcus aureus isolates in Ahvaz, Iran.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial
      pathogen. We sought to determine the frequency of the different types of SCCmec
      in MRSA isolates by performing a cross-sectional study. A total of 72 S. aureus
      isolates were collected from Imam Khomeini and Golestan hospitals and analysed
      for MRSA and SCCmec typing by multiplex PCR. The pattern of antibiotic resistance
      among S. aureus isolates was determined by disc diffusion analysis. Of the 72 S.
      aureus isolates, 29 (40.27%) were recognized as MRSA. SCCmec type III was the
      most common type, with 55.17% (16/29), followed by type II with 27.58% (8/29);
      type IV with 10.34% (3/29); and type I with 6.89% (2/29). All 29 MRSA isolates
      were resistant to chloramphenicol and erythromycin. In addition, resistance to
      cephalothin, gentamicin, clindamycin, ciprofloxacin, tetracycline and rifampicin
      was seen in 24 (75%), 26 (63.4%), 17 (94.4%), 27 (71.05%), 10 (71.42%) and 13
      (68.42%) MRSA isolates, respectively. A decreased sensitivity of MRSA to the
      antibiotics used was observed, with type III SCCmec being the predominant
      isolate.

PMID- 29379605
TI  - First report of isolation and antibiotic susceptibility pattern of Raoultella
      electrica from table eggs in Jaipur, India.
AB  - Raoultella electrica, a Gram-negative, non-spore-forming, rod-shaped facultative
      anaerobe, was identified during a regular investigation of bacterial
      contamination in table eggs in the winter season. A total of 165 hen's eggs were
      collected in the winter season from 15 different areas of the city of Jaipur,
      India. Gram-negative Enterobacteriales were isolated on selective and
      differential media by the conventional plate method and were further identified
      by several biochemical tests and 16S rRNA gene sequencing. Commonly prescribed
      antibiotics for enteric infection were used for antibiotic susceptibility
      testing. For isolated microorganisms, different resistance patterns were found
      against the different antibiotics used (p < 0.01). The multiple antibiotic
      resistance index of bacterial isolates ranged from 0.10 to 0.60. R. electrica
      strain 1GB/NBRC 109676/KCTC 32430 was isolated for the first time from commercial
      chicken's eggs.

PMID- 29379606
TI  - Escherichia hermannii as the sole pathogen in urosepsis: case report.

PMID- 29379607
TI  - Pioglitazone and cause-specific risk of mortality in patients with type 2
      diabetes: extended analysis from a European multidatabase cohort study.
AB  - Objectives: Describe and compare the risk of cardiovascular and non
      cardiovascular mortality in patients whose antidiabetic therapy is modified to
      include pioglitazone compared with an alternative antidiabetic medication at the
      same stage of disease progression. Research design and methods: This exploratory
      linked database cohort analysis used pooled health and mortality data from three
      European countries: Finland, Sweden and the UK. Propensity score together with
      exact matching was used to match 31 133 patients with type 2 diabetes first
      prescribed pioglitazone from 2000 to 2011, to 31 133 patients never prescribed
      pioglitazone. Exact matching variables were treatment stage, history of diabetes,
      diabetes complications and cardiovascular disease, and year of cohort entry. Mean
      follow-up time was 2.60 (SD 2.00) and 2.69 (SD 2.31) years in the pioglitazone
      and non-pioglitazone-exposed groups, respectively. Crude cause-specific mortality
      rates were ascertained. Association with pioglitazone use was estimated using Cox
      proportional hazards models adjusted a priori for country, age, sex, the
      propensity score quintile and time-dependent variables representing use of
      antidiabetic drugs. Stepwise testing identified no additional confounders to
      include in adjusted models. Results: The crude mortality rate was lower in the
      pioglitazone-exposed group than the non-exposed group for both cardiovascular and
      non-cardiovascular mortality. Adjusted HRs comparing pioglitazone to alternative
      antidiabetic exposure were 0.58 (95% CI 0.52 to 0.63) and 0.63 (95% CI 0.58 to
      0.68) for cardiovascular and non-cardiovascular mortality, respectively. A
      protective effect associated with pioglitazone was also found for all specific
      cardiovascular causes. Conclusions: This analysis suggests that pioglitazone is
      associated with a decrease in both cardiovascular and non-cardiovascular
      mortality. Results should be interpreted with caution due to the potential for
      residual confounding in this exploratory analysis. Further studies, specifically
      designed to test the association between pioglitazone use and patient-focused
      outcomes, are suggested. Study registration number: European Network of Centres
      for Pharmacoepidemiology and Pharmacovigilance (ENCePP; EUPAS3626).

PMID- 29379608
TI  - Trends in type 2 diabetes detection among adults in the USA, 1999-2014.
AB  - Objective: To examine recent trends in type 2 diabetes detection among adults in
      the USA. Research design and methods: We used data from the 1999-2014 National
      Health and Nutrition Examination Surveys on non-pregnant adults (aged >=18 years)
      not reporting a diagnosis of diabetes (n=16 644 participants, averaging about
      2000 for each 2-year cycle). We defined undiagnosed diabetes as a fasting plasma
      glucose >=126 mg/dL or a hemoglobin A1c >=6.5% (48 mmol/mol). We measured case
      detection as the probability of finding undiagnosed type 2 diabetes among the
      population without diagnosed diabetes. Linear regression models were used to
      examine trends overall and by sociodemographic characteristics (ie, age, gender,
      race/ethnicity, education, poverty-income ratio (PIR)). Results: Age-standardized
      probability of finding undiagnosed type 2 diabetes was 3.0% (95% CI 2.1% to 4.2%)
      during 1999-2000 and 2.8% (2.2%-3.6%) during 2013-2014 (P for trend=0.52).
      Probability increased among Mexican-Americans (P for trend=0.01) but decreased
      among adults aged 65 years or older (P for trend=0.04), non-Hispanic (NH) white
      (P for trend=0.02), and adults in the highest PIR tertile (P for trend=0.047).
      For all other sociodemographic groups, no significant trends were detected.
      Conclusions: We found little evidence of increased detection of undiagnosed type
      2 diabetes among adults in the USA during the past 15 years. Although
      improvements were seen among NH white, older, and wealthy adults, these
      improvements were not large. As the scope of primary prevention efforts
      increases, case detection may improve.

PMID- 29379609
TI  - Protocol for a multicentred randomised controlled trial investigating the use of
      personalised golimumab dosing tailored to inflammatory load in ulcerative
      colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve
      Response in Colitis) led by the INITIAtive group (NCT 0268772).
AB  - Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease
      (IBD), often leading to an impaired quality of life in affected patients. Current
      treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal
      antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several
      recent retrospective and prospective studies have demonstrated that fixed dosing
      schedules of anti-TNF agents often fails to consistently achieve adequate
      circulating therapeutic drug levels (DL) with consequent risk of immunogenicity
      treatment failure and potential risk of hospitalisation and colectomy in patients
      with UC.The design of GLM dose Optimisation to Adequate Levels to Achieve
      Response in Colitis aims to address the impact of dose escalation of GLM
      immediately following induction and during the subsequent maintenance phase in
      response to suboptimal DL or persisting inflammatory burden as represented by
      raised faecal calprotectin (FCP). Aim: The primary aim of the study is to
      ascertain if monitoring of FCP and DL of GLM to guide dose optimisation (during
      maintenance) improves rates of patient continuous clinical response and reduces
      disease activity in UC. Methods and analysis: A randomised, multicentred two-arm
      trial studying the effect of dose optimisation of GLM based on FCP and DL versus
      treatment as per SMPC. Eligible patients will be randomised in a 1:1 ratio to 1
      of 2 treatment groups and shall be treated over a period of 46 weeks. Ethics and
      dissemination: The study protocol was approved by the Research Ethics committee
      of St. Vincent's University Hospital. The results will be published in a peer
      reviewed journal and shared with the worldwide medical community. Trial
      registration numbers: EudraCT number: 2015-004724-62; Clinicaltrials.gov
      Identifier: NCT0268772; Pre-results.

PMID- 29379610
TI  - Health psychology: It's not what you do, it's the way that you do it.
AB  - Despite the growth in theoretical understandings of health behaviour and
      standardised approaches to health interventions (e.g. behaviour change
      taxonomies), health psychology has paid comparatively less attention to the
      importance of the implementation processes - 'how to' rather than 'what to' of
      such interventions. The clinical and interpersonal skills that often reflect
      these implementation processes are poorly defined within the health psychology
      literature. The level of proficiency in such skills expected of Health and Care
      Professions Council registered practitioner health psychologists is unclear and
      poorly documented within the UK training requirements. This article explores the
      potential impact of this and offers some pragmatic solutions.

PMID- 29379611
TI  - An examination of college student wellness: A research and liberal arts
      perspective.
AB  - Promoting wellness within academia reduces disease frequency and enhances overall
      health. This study examined wellness factors among undergraduate students
      attending a research university (n = 85) or a small liberal arts college (n =
      126). Participants were administered surveys which measured physical, emotional,
      social, intellectual, and occupational wellness. Significant institutional
      differences emerged on measures of physical and social wellness. When collapsed
      across academic institutions, students who were gainfully employed reported
      greater self-efficacy compared with unemployed students. Gender differences
      emerged on measures of physical and social well-being. Our findings support the
      need for targeted interventions that facilitate enhanced college student
      development and well-being.

PMID- 29379612
TI  - Two sides of the same coin and two routes for improvement: Integrating resilience
      and the social identity approach to well-being and ill-health.
AB  - We propose that resilience effectively helps people cope with stress, thus
      predominantly reducing the negative. However, we argue that individuals' social
      identification has the potential to contribute to their well-being, thus
      fostering the positive. A two-wave survey study of 180 students shows that
      resilience is more strongly (negatively) associated with ill-health (i.e. stress
      and depression), whereas social identification is more strongly (positively)
      related to well-being (i.e. satisfaction and work engagement). We believe that it
      is necessary to see these two routes to improving people's health as
      complementary, both in future research and for therapy and interventions.

PMID- 29379613
TI  - Does the Drug Facts Label for nonprescription drugs meet its design objectives? A
      new procedure for assessing label effectiveness.
AB  - We demonstrate an expanded procedure for assessing drug-label comprehension.
      Innovations include a pretest of drug preconceptions, verbal ability and label
      attentiveness measures, a label-scanning task, a free-recall test, category
      clustering measures, and preconception-change scores. In total, 55 female and 39
      male undergraduates read a facsimile Drug Facts Label for aspirin, a Cohesive
      Prose Label, or a Scrambled-Prose Label. The Drug Facts Label outperformed the
      Scrambled-Prose Label, but not the Cohesive-Prose Label, in scanning
      effectiveness. The Drug Facts Label was no better than the Cohesive-Prose Label
      or the Scrambled-Prose Label in promoting attentiveness, recall and organization
      of drug facts, or misconception refutation. Discussion focuses on the need for
      refutational labels based on a sequence-of-events text schema.

PMID- 29379614
TI  - Respiratory diseases in children attending kindergartens: Health-related
      variables and mothers' psychological, parental, and marital functioning.
AB  - This study aimed to examine the differences between mothers of children with and
      without respiratory problems in variables related to psychological, parental, and
      marital functioning and to determine which contributed more to parenting stress,
      because there is a lack of information in this field. Participants were 459
      mothers of children attending kindergartens, who accepted to participate. The
      instruments were The International Study of Asthma and Allergies in Childhood
      questionnaire, Hospital Anxiety and Depression Scale, Parenting Stress Index
      Short Form, Parenting Stress Index-Long Form, and Escala de Avaliacao da
      Satisfacao em Areas da Vida Conjugal. Anxiety, depression, and parenting stress
      were higher in the more symptomatic children and parenting stress was associated
      with anxiety, depression, and marital satisfaction. Findings support the
      relevance of children's respiratory-related variables to mothers' psychological,
      parental, and marital functioning.

PMID- 29379615
TI  - The third tier in treatment: Attending to the growing connection between gut
      health and emotional well-being.
AB  - The microbial environment of the human gut has powerful influence on immunity,
      metabolism, and obesity. There is now emerging evidence that the microbiome of
      our gastrointestinal system may also be a key factor impacting our emotional and
      behavioral health. The purpose of this article is to elucidate how this emerging
      area of science can further educate and encourage mental health professionals to
      explore an additional means to treatment. Since much of this research is found in
      the biological and neuroscientific literature, it can be quite cumbersome for
      clinicians to digest and apply, who would critically benefit from a concise
      discussion of the gut-brain connection.

PMID- 29379616
TI  - A qualitative exploration of the experiences of living with and being treated for
      fibromyalgia.
AB  - This study explores the life and treatment experience of people in the United
      Kingdom with fibromyalgia in order to inform the development of treatments which
      are both effective and acceptable to users. Qualitative interviews were conducted
      with 14 participants with interpretative phenomenological analysis used as the
      theoretical framework and analytical method. The themes identified were as
      follows: Inauthenticity of fibromyalgia, An Unconventional healthcare experience,
      Re-creating support networks, Challenging the working identity, Threatening the
      family dynamic and Fighting, accepting or accommodating? The biopsychosocial
      impacts of fibromyalgia disrupted the identity, lifestyle, roles and
      relationships of our participants with such challenges further exacerbated by the
      contested nature of the illness.

PMID- 29379617
TI  - 'Don't push me aside, Doctor': Suicide attempters talk about their support needs,
      service delivery and suicide prevention in South Africa.
AB  - Few studies have explored the expressed support needs of suicide attempters in
      developing countries. Data, collected via in-depth interviews with suicide
      attempters admitted to a South African hospital, were analysed using thematic
      content analysis. Participants explicitly asked for integrated psycho-social
      services at a primary health care level and say they require assistance with
      alleviating psychiatric symptoms, establishing connectedness, interpersonal
      conflict and solving socio-economic problems. Findings highlight the importance
      for suicide prevention of (1) considering interpersonal and contextual socio
      economic factors in addition to the psychiatric causes of suicidal behaviour; and
      (2) multilevel strategies, intersectoral collaboration and integrated person
      centred primary health care.

PMID- 29379618
TI  - Positive change and sense of coherence in Japanese mothers of children with
      congenital appearance malformation.
AB  - The purpose of this study was to clarify the factors related to perceived
      positive change and sense of coherence in mothers (n = 293) of children with
      cleft lip and palate. The strongest negative correlation with sense of coherence
      was stigmatizing words from others; there were positive correlations with social
      capital and perceived positive change. Multiple regression showed that to be
      aware of positive changes, mothers share their feelings with mothers in the same
      position, are rooted in a safe community and do not feel isolated in parenting.
      People who have experienced adversity may have the opportunity to enhance sense
      of coherence by obtaining perceived positive change.

PMID- 29379619
TI  - Comparisons of health-related and appearance-related smoking risk perceptions and
      worry on motivation to quit.
AB  - This research examined main and interactive associations of perceived risk and
      worry of health and appearance smoking consequences on motivation to quit and the
      relative importance of each of these. Hierarchical regressions controlling for
      other measures found that perceived conditional risk and worry of health
      consequences were associated with motivation to quit; only conditional risk of
      appearance consequences was associated with motivation to quit. Relative weights
      analysis indicated that perceived conditional risk of appearance consequences and
      worry about health consequences were the most important variables in the model.
      Consideration of appearance consequences may aid in motivating smokers to try
      quitting.

PMID- 29379620
TI  - Self-compassion and physical health: Exploring the roles of perceived stress and
      health-promoting behaviors.
AB  - Growing evidence indicates that self-compassion is associated with better
      physical health, but the pathways that mediate this relationship are not well
      understood. This study tested a serial mediation model that linked self
      compassion, perceived stress, health behaviors, and a comprehensive index of
      physical health. A sample of 176 individuals completed an online survey posted on
      Amazon's Mechanical Turk. Self-compassion had an indirect effect on physical
      health via both mediators and through the sequential pathway, suggesting that
      taking a kind, accepting and mindful stance toward one's flaws and failures may
      have benefits for reducing stress and promoting health behaviors.

PMID- 29379621
TI  - Validation of the English and French versions of the Brief Health Care Climate
      Questionnaire.
AB  - Patient autonomy is a central value in medicine and critical component of
      adherence to medical advice. This article reports on a validation of the 6-item
      version of the Health Care Climate Questionnaire (HCCQ), a measure of autonomy
      support in health care settings, in a sample of 242 melanoma patients. The HCCQ
      showed excellent internal consistency (alpha = .91), structural validity (Tucker
      Lewis index = .99; comparative fit index = .99; root mean square error of
      approximation = .06, 90 per cent confidence interval (.00, .11); standardized
      root mean square residual = .02; chi2 (8, N = 235) = 13.99, p = .08) and
      construct validity (92.31% of hypothesized correlations with other measures
      confirmed). Acceptable 3-month test-retest reliability was observed (r = .55, p <
      .001; intraclass correlation coefficient (A, 1) = .54, p < .001). The French
      version was found equivalent to the English version.

PMID- 29379622
TI  - Under what conditions can a nonprescription drug label serve as refutation text?
      The role of directed attention and processing strategy.
AB  - Nonprescription drug labels are relatively ineffective in refuting drug
      misconceptions. We sought to improve the effectiveness of an aspirin label as a
      refutation text by manipulating selective attention and label-processing
      strategy. After reading a facsimile label, those of 196 undergraduates who
      attempted to explain why shaded drug facts are "easily confused" recalled more
      refuting drug facts than participants who attempted to explain why those facts
      are "easily ignored." However, "easily confused" processing did not change truth
      ratings of misconceptions associated with those drug facts. We conclude that
      refuted misconceptions remain in memory but are inhibited by disconfirming drug
      facts.

PMID- 29379623
TI  - Distance mentoring of health researchers: Three case studies across the career
      development trajectory.
AB  - Despite the crucial role of mentoring, little literature exists that addresses
      distance mentoring among health researchers. This article provides three case
      studies showcasing proteges at different stages of career development (one in
      graduate school, one as an early-stage researcher, and one as an established
      researcher). Each case study provides a brief history of the relationship,
      examines the benefits and challenges of working together at a distance, and
      discusses the lessons learned from both the mentor and the protege over the
      course of these relationships. A mentoring model, examples of mentoring
      communications, and potential promising practices are also provided and
      discussed.

PMID- 29379624
TI  - Training pharmacists in the stage-of-change model of smoking cessation and
      motivational interviewing: A randomized controlled trial.
AB  - This study evaluated the effect of training pharmacists in the stage-of-change
      model for smoking cessation and motivational interviewing on smoking cessation
      outcomes. A training based on the stage-of-change model for smoking cessation and
      motivational interviewing was introduced to pharmacists. Pharmacists were
      randomly assigned to the intervention or control group. The control group
      attended a 3-hour training session, whereas the intervention group also attended
      a further 6-hour training session. At week 24, 12.2 percent of the smokers quit
      smoking in the intervention group, whereas 1.6 percent of the smokers quit
      smoking in the control group. The findings of this study showed that training
      pharmacists, in the stage-of-change model for smoking cessation and motivational
      interviewing, improves smoking reduction and cessation rates.

PMID- 29379625
TI  - Factor structure and psychometric properties of the Fertility Problem Inventory
      Short Form.
AB  - The study analyses factor structure and psychometric properties of the Italian
      version of the Fertility Problem Inventory-Short Form. A sample of 206 infertile
      couples completed the Italian version of Fertility Problem Inventory (46 items)
      with demographics, State Anxiety Scale of State-Trait Anxiety Inventory (Form Y),
      Edinburgh Depression Scale and Dyadic Adjustment Scale, used to assess convergent
      and discriminant validity. Confirmatory factor analysis was unsatisfactory
      (comparative fit index = 0.87; Tucker-Lewis Index = 0.83; root mean square error
      of approximation = 0.17), and Cronbach's alpha (0.95) revealed a redundancy of
      items. Exploratory factor analysis was carried out deleting cross-loading items,
      and Mokken scale analysis was applied to verify the items homogeneity within the
      reduced subscales of the questionnaire. The Fertility Problem Inventory-Short
      Form consists of 27 items, tapping four meaningful and reliable factors.
      Convergent and discriminant validity were confirmed. Findings indicated that the
      Fertility Problem Inventory-Short Form is a valid and reliable measure to assess
      infertility-related stress dimensions.

PMID- 29379626
TI  - Disease factors associated with spousal influence on diabetic diet: An
      exploratory comparison of Vietnamese American and White older adults.
AB  - This study examined whether disease-specific factors were important for how and
      how often White versus Vietnamese American spouses influenced their partners'
      diabetic diet. Results from a cross-sectional survey of 145 older adult spouses
      whose partners had type 2 diabetes revealed that Vietnamese American spouses used
      more frequent spousal influence (positive and negative) than White spouses. In
      addition, most of the factors associated with spousal influence differed for
      Vietnamese American and White spouses. Findings from this study highlight the
      importance of proximal and sociocultural factors in understanding older spouses'
      influence on their partners' diabetic diet.

PMID- 29379627
TI  - Psychometric properties of the Beliefs about Medicine Questionnaire-adjuvant
      endocrine therapy (BMQ-AET) for women taking AETs following early-stage breast
      cancer.
AB  - This study evaluated the Beliefs about Medicine Questionnaire to explore
      adherence to adjuvant endocrine therapy after treatment for breast cancer (BMQ
      AET). Factor structure of the BMQ-AET was explored alongside internal
      consistency, convergent validity and acceptability. The BMQ-AET Specific Scale
      fitted the original 10 item model. Internal consistency of the BMQ-AET was much
      improved compared to the original BMQ and convergent validity showed predicted
      direction of correlation, although correlation with BMQ-AET concerns scale was
      low. Acceptability was good. The evaluation of the BMQ-AET is encouraging, and
      could facilitate future research around adherence to AET.

PMID- 29379628
TI  - Associations of Thalassemia Major and satisfaction with quality of life: The
      mediating effect of social support.
AB  - The present research analyzed the elements of thalassemia which affect the
      patient's perceived quality of life. Three hundred patients with Thalassemia
      Major (males = 165, 55%; females = 135, 45%; Mage = 36.13, standard deviation =
      8.54) were the sample. Analysis of multiple mediations revealed a direct effect
      of self-efficacy on the Satisfaction with Life Scale that is mediated only by
      social support.The findings suggest a need to accentuate help and support to
      patients with Thalassemia Major.

PMID- 29379629
TI  - The development of a narrative describing the bereavement of families of
      potential organ donors: A systematic review.
AB  - Families of potential post-mortem organ donors face various challenges in the
      unfamiliar hospital context and after returning home. This review of sources
      published between 1968 and 2017 seeks to understand their journey as a
      bereavement experience with a number of unique features. Grief theory was used to
      identify ways that staff can assist family members to tolerate ambiguities and
      vulnerabilities while contributing to an environment characterised by compassion
      and social inclusion. Staff can guide families and create opportunities for
      meaningful participation, building resilience and developing bereavement-related
      skills that could assist them in the months that follow.

PMID- 29379631
TI  - Validation of the Paranormal Health Beliefs Scale for adults.
AB  - We present the validation study of the Paranormal Health Beliefs Scale adult
      version, aimed to measure illusory beliefs about health. The scale was
      administered to 643 participants (54.3% females), having an average age of 29.7
      years (standard deviation = 18.31). The results of the analyses confirmed the
      dimensions of the Paranormal Health Beliefs Scale as developed in the previous
      adolescent study (Beliefs: Religious, Superstitious, in Extraordinary Events,
      Parapsychological, and Pseudo-scientific of a biomedical nature), as well as the
      convergent and discriminant validity through the correlation with other
      constructs (locus of control and self-efficacy). The results also showed
      significant differences between subgroups by gender and age. The Paranormal
      Health Beliefs Scale shows satisfactory psychometric properties and thus may be
      used effectively to identify the varied range of illusory beliefs related to
      health, even within the context of lifelong educational programs aimed at health
      promotion.

PMID- 29379630
TI  - The Opioid Abuse Risk Screener predicts aberrant same-day urine drug tests and 1
      year controlled substance database checks: A brief report.
AB  - The Opioid Abuse Risk Screener was developed to support well-informed decision
      making in opioid analgesic prescribing by extending the breadth of psychiatric
      risk factors evaluated relative to other non-clinician-administered measures. We
      examined the preliminary predictive validity of the Opioid Abuse Risk Screener
      relative to the widely used Screener and Opioid Assessment for Patients with Pain
      Revised in predicting aberrant urine drug tests and controlled substance database
      checks. The Opioid Abuse Risk Screener is significantly different from the
      Screener and Opioid Assessment for Patients with Pain-Revised in predicting
      aberrant same-day urine drug tests (Z = 2.912, p = 0.0036) and controlled
      substance database checks within 1 year of assessment (Z = 3.731, p = 0.0002).
      Promising preliminary analyses using machine learning methods are also discussed.

PMID- 29379632
TI  - Family functioning and trait emotional intelligence among youth.
AB  - This study explored the relationship between family functioning and trait
      emotional intelligence among 547 respondents, between the age of 16 and 24 years
      from Malaysia, Iran, China, Sudan, Somalia, Morocco, the United Kingdom, Germany
      and the Netherlands. The questionnaires were Family Adaptability and Cohesion
      Evaluation Scale III and Trait Emotional Intelligence Questionnaire Short Form.
      Pearson correlation analysis revealed a significant relationship between family
      functioning and trait emotional intelligence. The higher the family functioning,
      the higher the trait emotional intelligence among youths. The findings provide a
      deeper understanding in the field of family functioning and trait emotional
      intelligence and have implications for parents, administrators and child
      relationships dealing with trait emotional intelligence.

PMID- 29379634
TI  - Life as an early career researcher: interview with Minhaj Sirajuddin.
AB  - Minhaj Sirajuddin talks to Francesca Lake, Head of Open Access Publishing. Minhaj
      Sirajuddin is currently an Assistant Investigator at the Institute for Stem Cell
      Biology and Regenerative Medicine (InStem), Bangalore, India. His lab works on
      understanding biological motility mediated by cytoskeleton elements using
      biophysics and cell biology. Previously his tenures were at UCSF (CA, USA) for
      his postdoctoral work and the Max Planck Institute (Dortmund, Germany) for his
      PhD. Minhaj is a recipient of Wellcome Trust - DBT India Alliance Intermediate
      Fellowship and the EMBO Young Investigator Award. He was also a finalist in the
      inaugural Future Science Early Career Research Award.

PMID- 29379635
TI  - Reducing the osteoporosis treatment gap: an interview with UCB's Pascale
      Richetta.
AB  - Dr. Pascale Richetta is Executive Vice President and Head of the Bone Patient
      Value Unit at UCB (Brussels, Belgium). She joined UCB in 2016 following over 20
      years' experience in the pharma and biotech industry. After completing her MD at
      the University of Poitiers (France), she spent time as vice president at
      Abbvie/Abbott and has also held positions at GlaxoSmithKline, Ipsen and Servier.
      Through the course of her career she acquired impressive commercial experience
      managing both traditional pharmaceuticals and complex biologics and her knowledge
      of markets around the world is key to helping UCB prepare for future product
      launches.

PMID- 29379633
TI  - In vitro and in vivo anticandidal activities of alginate-enclosed chitosan
      calcium phosphate-loaded Fe-bovine lactoferrin nanocapsules.
AB  - Aim: To study the in vitro and in vivo anticandidal activity of nanocapsulated
      bovine lactoferrin. Materials & methods: In vitro and in vivo antimicrobial
      activities were conducted to study the anticandidal activities of nanocapsules
      (NCs). Results: The NCs showed good anticandidal activities. The disruption of
      cell wall and cell membrane was noted via microscopy studies. The NCs changed the
      normal growth profile of Candida albicans. NCs reduced the colony forming unit in
      kidney and blood samples. Histopathological examination showed better cell
      structure and coordination compared with untreated mice kidney. NCs also enhanced
      the natural killing properties of C. albicans by epithelial cells. Conclusion:
      NCs have effective anticandidal properties and have the potential as a
      therapeutic agent against candidiasis.

PMID- 29379636
TI  - Could IGF-I levels play a neuroprotective role in patients with large vestibular
      schwannomas?
AB  - Aim: To evaluate the possible superiority of outcome in patients with elevated
      IGF-I levels after vestibular schwannoma (VS) resection. Patients & methods: This
      retrospective study included 65 patients (34 male, 52.3%) with VS operated in
      between January 2009 and April 2014 (follow-up 3.2 +/- 0.7 years). Preoperative
      or postoperative IGF-I levels were identified for each patient. Results: Patients
      were divided into two groups: Group A (small size tumor), 56 patients; and Group
      B (large size tumor), 9 cases. IGF-I levels in Group A (195.8 +/- 32.9 ng/ml)
      were compared with those of Group B (242.2 +/- 22.2 ng/ml) and were found to have
      statistically significant difference (p = 0.001). Conclusion: Increased IGF-I
      levels could hold a key role in nerve recovery in patients undergoing surgical
      resection of large VS.

PMID- 29379637
TI  - Stabilizers influence drug-polymer interactions and physicochemical properties of
      disulfiram-loaded poly-lactide-co-glycolide nanoparticles.
AB  - Aim: Stabilizers are known to be an integral component of polymeric
      nanostructures. Ideally, they manipulate physicochemical properties of
      nanoparticles. Based on this hypothesis, we demonstrated that disulfiram (drug)
      and Poly-lactide-co-glycolide (polymer) interactions and physicochemical
      properties of their nanoparticles formulations are significantly influenced by
      the choice of stabilizers. Methodology: Electron microscopy, differential
      scanning calorimetry, x-ray diffraction, Raman spectrum analysis, isothermal
      titration calorimetry and in silico docking studies were performed. Results &
      discussion: Polysorbate 80 imparted highest crystallinity while Triton-X 100
      imparted highest rigidity, possibly influencing drug bioavailability, blood
      retention time, cellular uptake and sustained drug release. All the molecular
      interactions were hydrophobic in nature and entropy driven. Therefore, polymeric
      nanoparticles may be critically manipulated to streamline the passive targeting
      of drug-loaded nanoparticles.

PMID- 29379638
TI  - Leiomyosarcoma of the stomach with metastasis to the liver: a case report with
      review of the literature.
AB  - Leiomyosarcoma of the stomach is a very rare malignancy that was not
      distinguished from the more frequent gastrointestinal stromal tumors until early
      2000s. Here we report on a case of a metastatic disease that developed in a 47
      year-old man 2 years after he was diagnosed with the primary tumor and treated
      with curative surgical excision and adjuvant doxorubicin. The primary and
      metastatic lesions were positive for smooth muscle markers alpha-smooth muscle
      actin and h-caldesmon and negative for CD117, DOG-1 and S100 by
      immunohistochemistry. Metastatic disease progressed on additional monotherapy
      with doxorubicin and docetaxel-gemcitabine combination, and stable disease was
      achieved upon treatment with pazopanib. Patient is surviving 35 months since
      diagnosis of the primary tumor and 11 months since diagnosis of metastatic
      disease.

PMID- 29379639
TI  - DNA demethylation marks in chronic lymphocytic leukemia: it is time to let the
      cat out of the bag.

PMID- 29379640
TI  - A prospective clinical study of the implications of IL-8 in the diagnosis,
      aggressiveness and prognosis of prostate cancer.
AB  - Aim: We evaluated the relationship between IL-8 and prostate cancer (PCa) with
      emphasis on diagnosis, aggressiveness and prognosis. Materials & methods:
      Prostate-specific antigen (PSA) and serum IL-8 were collected from patients
      undergoing prostate biopsy. IL-8 expression was evaluated on immunohistochemistry
      with IL-8 labeling index. Complete follow-up of this cohort was achieved over a
      period of up to 6 years with continuous follow-up of PSA levels. Results: Among
      135 patients, serum IL-8 level did not correlate to the diagnosis or
      aggressiveness of PCa. In 52 radical prostatectomy specimens, a higher IL-8
      labeling index was detected in the tumor areas (0.4 +/- 0.2 vs 0.33 +/- 0.2; p =
      0,007) but did not correlate to any of the prognostic markers: D'Amico
      classification (p = 0.52), Gleason score (p = 0.45), perineural (p = 0.83) and
      capsular invasion (p = 0.75). No correlation was found to PSA biochemical-free
      failure. Conclusion: IL-8 serum level was not a significant predictor of
      diagnosis, aggressiveness or prognosis of PCa.

PMID- 29379641
TI  - Computational design of new molecular scaffolds for medicinal chemistry, part II:
      generalization of analog series-based scaffolds.
AB  - Aim: Extending and generalizing the computational concept of analog series-based
      (ASB) scaffolds. Materials & methods: Methodological modifications were
      introduced to further increase the coverage of analog series (ASs) and compounds
      by ASB scaffolds. From bioactive compounds, ASs were systematically extracted and
      second-generation ASB scaffolds isolated. Results: More than 20,000 second
      generation ASB scaffolds with single or multiple substitution sites were
      extracted from active compounds, achieving more than 90% coverage of ASs.
      Conclusion: Generalization of the ASB scaffold approach has yielded a large
      knowledge base of scaffold-capturing compound series and target information.

PMID- 29379642
TI  - Future biomaterials for enhanced cell-substrate communication in spinal cord
      injury intervention.

PMID- 29379643
TI  - 'Et tu, inhibitor?': the potential for HIV inhibitors to prime P-gp-mediated
      chemoresistance in cancer.

PMID- 29379644
TI  - Update on new research in Gram-negative infections European Congress of Clinical
      Microbiology and Infectious Diseases 2017 (22-25 April, Vienna, Austria).
AB  - European Congress of Clinical Microbiology and Infectious Diseases 2017 (22-25
      April, Vienna, Austria). Collaborative studies between hospitals in Europe and
      across the USA provided new insights into assessing susceptibility patterns and
      optimizing antimicrobial therapy in patients with infections caused by Gram
      negative bacteria, including carbapenemase-producing Enterobacteriaceae (CPE) and
      Pseudomonas aeruginosa.

PMID- 29379645
TI  - Evaluation of the free-radical scavenging and antioxidant activities of Chilauni,
      Schima wallichii Korth in vitro.
AB  - Aim: Free radicals are an outcome of various metabolic activities and their
      excess production leads to many diseases. Therefore, it is necessary to
      neutralize excess free radicals. Materials & methods: Free-radical scavenging
      activity of various extracts of Schima wallichii was evaluated using standard
      protocols. Results: Chloroform, ethanol and aqueous extracts of S. wallichii
      scavenged DPPH, hydroxyl, superoxide, nitric oxide and ABTS free radicals and
      increased ferric-reducing antioxidant potential in a concentration-dependent
      manner. A total of 1000 MUg/ml of all the extracts and ethanol extract showed
      highest total flavonoids and phenol contents, respectively. Conclusion: The
      different extracts of S. wallichii scavenged different free radicals efficiently
      due to the presence of flavonoids and polyphenols and may be helpful in free
      radical-induced diseases.

PMID- 29379646
TI  - Interface of health and trade: a view point from health diplomacy.

PMID- 29379647
TI  - Decade of action on nutrition: our window to act on the double burden of
      malnutrition.

PMID- 29379648
TI  - Global action on the social determinants of health.
AB  - Action on the social determinants of health (SDH) is required to reduce
      inequities in health. This article summarises global progress, largely in terms
      of commitments and strategies. It is clear that there is widespread support for a
      SDH approach across the world, from global political commitment to within country
      action. Inequities in the conditions in which people are born, live, work and
      age, are however driven by inequities in power, money and resources. Political,
      economic and resource distribution decisions made outside the health sector need
      to consider health as an outcome across the social distribution as opposed to a
      focus solely on increasing productivity. A health in all policies approach can go
      some way to ensure this consideration, and we present evidence that some
      countries are taking this approach, however given entrenched inequalities, there
      is some way to go. Measuring progress on the SDH globally will be key to future
      development of successful policies and implementation plans, enabling the
      identification and sharing of best practice. WHO work to align measures with the
      sustainable development goals will help to forward progress measurement.

PMID- 29379649
TI  - How will the sustainable development goals deliver changes in well-being? A
      systematic review and meta-analysis to investigate whether WHOQOL-BREF scores
      respond to change.
AB  - Introduction: The Sustainable Development Goals (SDGs) 2015 aim to '...promote
      well-being for all', but this has raised questions about how its targets will be
      evaluated. A cross-cultural measure of subjective perspectives is needed to
      complement objective indicators in showing whether SDGs improve well-being. The
      WHOQOL-BREF offers a short, generic, subjective quality of life (QoL) measure,
      developed with lay people in 15 cultures worldwide; 25 important dimensions are
      scored in environmental, social, physical and psychological domains. Although
      validity and reliability are demonstrated, clarity is needed on whether scores
      respond sensitively to changes induced by treatments, interventions and major
      life events. We address this aim. Methods: The WHOQOL-BREF responsiveness
      literature was systematically searched (Web of Science, PubMed, EMBASE and
      Medline). From 117 papers, 15 (24 studies) (n=2084) were included in a meta
      analysis. Effect sizes (Cohen's d) assessed whether domain scores changed
      significantly during interventions/events, and whether such changes are relevant
      and meaningful to managing clinical and social change. Results: Scores changed
      significantly over time on all domains: small to moderate for physical (d=0.37;
      CI 0.25 to 0.49) and psychological QoL (d=0.22; CI 0.14 to 0.30), and small for
      social (d=0.10; CI 0.05 to 0.15) and environmental QoL (d=0.12; CI 0.06 to 0.18).
      More importantly, effect size was significant for every domain (p<0.001),
      indicating clinically relevant change, even when differences are small. Domains
      remained equally responsive regardless of sample age, gender and evaluation
      interval. Conclusion: International evidence from 11 cultures shows that all
      WHOQOL-BREF domains detect relevant, meaningful change, indicating its
      suitability to assess SDG well-being targets.

PMID- 29379650
TI  - Strengthening global health security by embedding the International Health
      Regulations requirements into national health systems.
AB  - The International Health Regulations (IHR) 2005, as the overarching instrument
      for global health security, are designed to prevent and cope with major
      international public health threats. But poor implementation in countries hampers
      their effectiveness. In the wake of a number of major international health
      crises, such as the 2014 Ebola and 2016 Zika outbreaks, and the findings of a
      number of high-level assessments of the global response to these crises, it has
      become clear that there is a need for more joined-up thinking between health
      system strengthening activities and health security efforts for prevention, alert
      and response. WHO is working directly with its Member States to promote this
      approach, more specifically around how to better embed the IHR (2005) core
      capacities into the main health system functions. This paper looks at how and
      where the intersections between the IHR and the health system can be best
      leveraged towards developing greater health system resilience. This merging of
      approaches is a key component in pursuit of Universal Health Coverage and
      strengthened global health security as two mutually reinforcing agendas.

PMID- 29379651
TI  - Intra-Abdominal Hydatid Cyst: Sociodemographics, Clinical Profiles, and Outcomes
      of Patients Operated on at a Tertiary Hospital in Addis Ababa, Ethiopia.
AB  - Background: Hydatid cyst is caused by the tapeworm Echinococcus granulosus. The
      abdomen, specifically the liver, is the most common site affected. Objective:
      Determine the presentation patterns, types of surgical management, and outcomes
      of patients operated for intra-abdominal hydatid cyst (IAHC). Methodology: A
      retrospective descriptive study of patients admitted and operated for IAHC from
      September 1, 2011, to August 31, 2015. Results: Forty-two patients whose age
      ranged from 10 to 65 (mean of 37 years) were operated on. Females comprised 27
      (64.3%) of the patients. The commonest presenting complaint was abdominal pain
      (41, 97.6%). Abdominal mass was documented in 23 (54.7%) cases. Abdominal
      ultrasound (AUS) and CT were the main imaging studies done on 38 (90.5%) and 24
      (57.1%) patients, respectively. Cysts measuring more than 10 cm in diameter were
      the most common finding in both studies. Liver was the primary site involved, 30
      (71.4%) cases, the right lobe being the main side, 73%. Thirty-eight (90.5%)
      patients underwent deroofing, evacuation, marsupialization, and omentoplasty
      (DEMO). There was no perioperative death, but 4 (9.5%) of the patients had post
      op complications. Conclusion: Abdominal pain was the most common presenting
      complaint. AUS and CT remain the preferred imaging. DEMO was the most common
      surgery.

PMID- 29379652
TI  - Autologous Platelet-Rich Plasma Eye Drops for the Treatment of Post-LASIK Chronic
      Ocular Surface Syndrome.
AB  - Purpose: To evaluate the efficacy of autologous platelet-rich plasma (E-PRP) eye
      drops for the treatment of chronic ocular surface syndrome (OSS) following laser
      in situ keratomileusis (LASIK). Methods: This prospective interventional
      consecutive clinical study include 156 eyes of 80 patients affected by post-LASIK
      chronic OSS who were treated with autologous E-PRP 6 times a day as monotherapy
      for 6 weeks. Results: Dry eye symptoms improved in 85% of the cases. A decrease
      in at least one quadrant to total disappearance on CFS was observed in 89.6% of
      the patients who had positive CFS before treatment. Three eyes presented severe
      punctate keratitis (1.9%) at baseline, all of which healed completely.
      Conjunctival hyperemia improved in 93.3% of the patients with previous signs of
      ocular surface inflammation. There was a significant improvement in logMAR CDVA
      from 0.14 +/- 0.19 to 0.06 +/- 0.12 (p = 0.000), and 74 (71.4%) eyes improved at
      least 1 line in CDVA. Conclusion: Monotherapy with autologous E-PRP is a well
      tolerated, safe, and effective treatment for the management of post-LASIK ocular
      surface syndrome. Precis: Monotherapy with autologous platelet-rich plasma eye
      drops has been shown to be an adequate option for the treatment of post-LASIK
      chronic ocular surface syndrome. This trial is registered with NCT03322917.

PMID- 29379653
TI  - Sensitivity, Specificity, and Limitations of Optical Coherence Tomography
      Angiography in Diagnosis of Polypoidal Choroidal Vasculopathy.
AB  - Purpose: To evaluate the sensitivity and specificity of optical coherence
      tomography angiography (OCTA) in differentiating polypoidal choroidal
      vasculopathy (PCV) from age-related macular degeneration (AMD). Methods: Fundus
      color photographs, spectral-domain optical coherence tomography, and fluorescein
      angiography (step 1) and OCTA (step 2) of 50 eyes that had PCV or AMD were
      presented to two ophthalmologists. The final diagnoses of PCV were masked.
      Sensitivity and specificity were calculated and compared to the 2-step approach
      (before and after OCTA) in detecting PCV. The limitations were also evaluated.
      Results: Of the 50 eyes, 31 were PCV and 19 were non-PCV. The sensitivity
      increased from 69.5% to 90% after OCTA; however, there was no significant
      improvement in specificity after OCTA. 70.9% of the eyes with PCV had clear or
      obvious branching vascular nets (BVNs) in OCTA with high sensitivity (97.5%)
      after OCTA. Contrarily, 29.1% had insignificant BVNs with a low sensitivity
      (72.5%) after OCTA. 27% of the occult choroidal neovascularization (CNV) cases
      were overdiagnosed as PCV when OCTA was applied. Conclusions: OCTA based on clear
      BVNs at the choroidal level increased sensitivity of diagnosis of PCV by 20%.
      However, the false-positive rate also increased in occult CNV. Several
      limitations for a correct diagnosis of PCV were noted.

PMID- 29379654
TI  - Determinants of Quality of Work Life among Nurses Working in Hawassa Town Public
      Health Facilities, South Ethiopia: A Cross-Sectional Study.
AB  - Background: A high quality of work life (QWL) is a crucial issue for health care
      facilities to have qualified, dedicated, and inspired employees. Among different
      specialties in health care settings, nurses have a major share among other health
      care providers. So, they should experience a better QWL to deliver high-quality
      holistic care to those who need help. Objective: To assess the level of quality
      of work life and its predictors among nurses working in Hawassa town public
      health facilities, South Ethiopia. Methods: A facility based cross-sectional
      study was conducted on 253 nurses of two hospitals and nine health centers. The
      total sample size was allocated to each facility based on the number of nurses in
      each facility. Data were collected using a structured questionnaire. The
      interitem consistency of the scale used to measure QWL had Cronbach's alpha value
      of 0.86. A multinomial logistic regression model was fitted to identify
      significant predictors of quality of work life using SPSS version 20. Results:
      The study showed that 67.2% of the nurses were dissatisfied with the quality of
      their work life. We found that educational status, monthly income, working unit,
      and work environment were strong predictors of quality of work life among nurses
      (p < 0.05). Conclusion: Significant proportions of the nurses were dissatisfied
      with the quality of their work life. The findings in this study and studies
      reported from elsewhere pinpoint that perception of nurses about the quality of
      their work life can be modified if health care managers are considerate of the
      key issues surrounding QWL.

PMID- 29379655
TI  - Genetic Variants in CSMD1 Gene Are Associated with Cognitive Performance in
      Normal Elderly Population.
AB  - Recently, genetic markers rs10503253 and rs2616984 in the CUB and Sushi multiple
      domains-1 (CSMD1) gene have been reported to be associated with schizophrenia and
      cognitive functions in genome-wide association studies. We examined the
      associations of the above SNPs with cognitive performance evaluated by the
      Montreal Cognitive Assessment (MoCA) tool in a cohort of the normal elderly from
      the Russian population. Significant association of rs2616984 genotypes with the
      MoCA scores was found using nonparametric analysis. No association of rs10503253
      with MoCA scores was observed using both parametric and nonparametric statistics.
      Significant combined effect of two-locus CSMD1 genotypes on MoCA scores was
      demonstrated by median test. Allele "A" and genotype "AA" of rs2616984 were
      significantly associated with the lower MoCA scores in comparison of 1st and 4th
      quartiles of MoCA total score distribution. The results suggest that genetic
      variants in CSMD1 gene are likely a part of genetic component of cognitive
      performance in the elderly.

PMID- 29379656
TI  - Deep Venous Thrombosis and Bilateral Pulmonary Embolism Revealing Silent Celiac
      Disease: Case Report and Review of the Literature.
AB  - Celiac disease (CD) is a systemic, chronic autoimmune disease that occurs in
      genetically predisposed individuals following dietary gluten exposure. CD can
      present with a wide range of gastrointestinal and extraintestinal manifestations
      and requires lifelong adherence to a gluten-free diet [GFD]. Venous
      thromboembolism (VTE) as a presentation of celiac disease is unusual and rarely
      reported. We present a case of a 46-year-old man who was admitted for shortness
      of breath and pleuritic chest pain and was found to have iron deficiency anemia,
      deep venous thrombosis, and bilateral pulmonary emboli (PE). After work-up for
      his anemia, the patient was diagnosed with CD. Comprehensive investigation for
      inherited or acquired prothrombotic disorders was negative. It is becoming
      increasingly recognized that CD is associated with an increased risk for VTE. PE,
      however, as a presentation of CD is exceedingly rare and to the best of our
      knowledge this is the third case report of such an occurrence and the only case
      report of a patient from North America. It is important to recognize that the
      first symptoms or signs of celiac disease might be extraintestinal. Furthermore,
      VTE as a presentation of CD is rare but life-threatening.

PMID- 29379657
TI  - Coats' Disease-Related Macular Edema Treated with Combined Aflibercept and Laser
      Photocoagulation.
AB  - Purpose: To describe the clinical response of refractory macular edema associated
      with Coats' disease following treatment with aflibercept and laser
      photocoagulation. Methods: Case report. Results: A 17-year-old female presented
      with decreased vision of the left eye. Ophthalmic exam demonstrated intraretinal
      hemorrhages and exudation with associated edema centrally. Angiographic
      evaluation revealed central leaking microaneurysms and peripheral capillary
      dropout. These findings and a systemic work-up that yielded an incidental Factor
      V Leiden mutation lead to a diagnosis of Coats' disease. Initial treatment
      consisted of laser photocoagulation and intravitreal bevacizumab but with poor
      response. Switching to intravitreal aflibercept resulted in resolution of the
      refractory macular edema and improvement of visual acuity to 20/25 in the left
      eye. Conclusion: We describe a case of refractory macular edema which responded
      more favorably to intravitreal aflibercept compared with bevacizumab when
      combined with laser photocoagulation in a patient with Coats' disease.

PMID- 29379658
TI  - Teratoid Cyst of the Postauricular Region: The First Ever Case Report.
AB  - Rudolf Virchow is considered to be the first scientist to have used the word
      sebaceous cyst. It was thought that these lesions occurred due to retention of
      sebaceous secretion consequent to obstruction of sebaceous ducts of sebaceous
      glands, although that was found not to be the case. In all these cysts, the
      cavity is filled with keratin. There are six types of keratin-filled cysts,
      namely, epidermoid, dermoid, teratoid, keratinous, trichilemmal, and teratoma
      cyst, which have one common name "dermoid cyst." Of the six, teratoid cyst is the
      least common. In contrast to other dermoid cysts, teratoid cysts contain tissue
      elements derived from all the three germ layers, namely, ectoderm, mesoderm, and
      endoderm. Teratomas can be differentiated from teratoid cysts by the fact that
      recognizable organ structures may be found in the former; examples include teeth
      and skin. Teratoid cysts can develop anywhere in the body but rarely arise in the
      head and neck region. They have never been reported in the postauricular region.
      In this case report, we present a case of teratoid cyst in the postauricular
      region in a 21-year-old female. The significance of this case lies in its rarity.

PMID- 29379659
TI  - Thyrotoxic Atrial Fibrillation: Factors Associated with Persistence and Risk of
      Ischemic Stroke.
AB  - Background: Atrial fibrillation (AF) is one of the commonest cardiovascular
      manifestations of thyrotoxicosis. A significant proportion of patients have
      persistent AF which may have long term consequences, for example, ischemic
      stroke. Methods: We performed a retrospective cohort study in a regional hospital
      from January 2004 to June 2016 to examine the clinical characteristics and
      outcomes of thyrotoxic patients who presented with atrial fibrillation and to
      investigate possible factors associated with persistent atrial fibrillation and
      ischemic stoke. Results: Among 1918 patients who had a diagnosis of
      thyrotoxicosis, 133 (6.9%) patients presented with AF. Spontaneous sinus
      conversion occurred in 89 (66.9%) patients in which 85 (94%) patients developed
      sinus conversion before or within 6 months after having achieved euthyroidism.
      The remaining 44 (33.1%) had persistent AF. The rate of ischemic stroke was
      numerically higher among patients who had persistent AF than those with
      spontaneous sinus conversion (15.9% versus 10.1%; log-rank 0.442, p = 0.506).
      Patients who sustained an ischemic stroke were older (71 +/- 11 years versus 62
      +/- 16 years, p = 0.023) and had a trend towards higher CHA2DS2-VASc score (2.9
      +/- 1.7 versus 2.3 +/- 1.7, p = 0.153). History of smoking (adjusted odds ratio
      4.9, 95% CI [1.8,14.0], p = 0.002), a larger left atrial diameter (adjusted odd
      ratio 2.6, 95% CI [1.2,5.5], p = 0.014), and a relatively lower free thyroxine
      level at diagnosis (adjusted odd ratio 2.1, 95% CI [1.2,3.5], p = 0.008) were
      associated with persistence of AF on multivariate analysis. Conclusion:
      Persistence of thyrotoxic AF occurred in one-third of patients and spontaneous
      sinus conversion was unlikely after six months of euthyroidism. High rate of
      ischemic stroke was observed among patients with persistent thyrotoxic AF and
      older age. Patients with factors associated with persistent AF, especially older
      people, should be closely monitored beyond 6 months so that anticoagulation can
      be initiated in a timely manner to reduce risk of ischemic stroke.

PMID- 29379660
TI  - Comparison of corifollitropin alfa and daily recombinant follicle-stimulating
      hormone in poor responder patients undergoing in vitro fertilization cycles.
AB  - Objective: The aim of this study was to compare the effect of corifollitropin
      alfa (CFA) and recombinant follicle-stimulating hormone (rFSH) in poor-responder
      patients undergoing antagonist cycles. Materials and Methods: The study was a
      retrospective analysis of the treatment results of 214 poor responder patients
      who had been admitted to the In Vitro Fertilization Unit of Izmir Medical Park
      Hospital between November 2014 and November 2016. Intracytoplasmic sperm
      injections were performed in 38 patients (group 1) with CFA, and the remaining
      176 (group 2) with rFSH for controlled ovarian hyperstimulation. Results: The
      age, body mass index, anti-mullerian hormone level, duration of infertility,
      duration of induction and antral follicle number were similar in the two groups.
      There was no difference in the total aspirated oocyte counts, mature oocyte
      ratio, fertilization rate, implantation rate, and clinical pregnancy rates
      between the two groups. The implantation rate was 9/38 (23.6%) in group 1 and
      42/176 (23.8%) in group 2, whereas the clinical pregnancy rates were 16.3% and
      17.2%, respectively. Conclusion: No difference was found in terms of oocyte
      count, fertilization rate, implantation rate, and clinical pregnancy rates of CFA
      or rFSH use in the antagonist cycles in poor-responder patients.

PMID- 29379661
TI  - Role of positron emission tomography-computed tomography in endometrial cancer.
AB  - Objective: The efficacy of preoperative 18F-fluoro-D-glucose (18F-FDG) positron
      emission tomography-computed tomography (PET-CT) in endometrium cancer is
      controversial. We examined the efficacy of PET-CT and the association between
      maximum standardized uptake value (SUVmax) and prognostic factors in endometrial
      cancer. Materials and Methods: Thirty patients with endometrial cancer underwent
      preoperative 18F-FDG/PET-CT. The patients were treated with abdominal
      hysterectomy with bilateral salpingo-oophorectomy, and bilateral systemic pelvic
      lymphadenectomy was planned for all patients; paraaortic lymphadenectomy was
      performed in patients with intermediate and high risk. Tumor histology, grade,
      depth of myometrial invasion, maximum tumor diameter, lymphovascular invasion,
      nodal status, and ovarian/adnexal metastases were recorded. Results: The mean
      primary tumor diameter was reported smaller in PET-CT and the effect size of PET
      CT was -0.60. The kappa value was 0.06 for myometrial invasion. Pelvic lymph node
      metastasis was reported in 22.2% of patients in PET-CT. However, 3.7% of patients
      had pelvic lymph node metastasis. The kappa value for pelvic lymph node
      metastasis was 0.23, and sensitivity, specificity, and positive and negative
      predictive values were 100%, 80.7%, 16.6%, and 100%, respectively. Paraaortic
      lymph node metastasis in PET-CT was suspected in 10%. However, paraaortic lymph
      node metastasis was found in 6.7% in histopathologic analyses. The kappa value
      was 0.15. The sensitivity, specificity, and positive and negative predictive
      values of PET-CT for detecting paraaortic lymph node metastases were 100%, 93.7%,
      66.6%, and 100%, respectively. Myometrial invasion and tumor diameter were the
      only important prognostic factors affecting SUVmax. Conclusion: According to our
      results, PET-CT has a limited role and diagnostic efficacy in endometrial cancer.
      The indications of FDG/PET-CT in endometrium cancer should be studied further and
      revised.

PMID- 29379662
TI  - A comparison of normal and high post-void residual urine and urodynamic
      parameters in women with overactive bladder.
AB  - Objective: To investigate voiding functions and assess the relationships of
      voiding parameters to overactive bladder symptoms and postvoiding residue
      volumes. Materials and Methods: This is a retrospective study analyzing
      urodynamic parameters in patients who were diagnosed as having overactive in our
      urogynecology clinic between April 2014 and April 2016. A total of 290 women who
      met the selection criteria were included in the study. The patients were divided
      into two groups according to postvoiding residue volumes: group 1, postvoiding
      residue volumes <100 mL (n=135); group 2, postvoiding residue volumes >=100 mL
      (n=155). Results: A total of 290 women were included in the study; the mean age
      was 71.4 years. A total of 158 (54.5%) patients had detrusor over-activity during
      urodynamic testing. The mean maximum bladder capacity in elevated group 2
      (postvoiding residue volumes >=100 mL) was significantly higher than in group 1
      (postvoiding residue volumes <100 mL) (p<0.01). Additionally, there was a
      significant difference between detrusor pressure at Qmax in both study groups
      (p<0.05). There were no significant differences in the first-sensation volume
      between the normal and elevated postvoiding residue volumes groups. Conclusion:
      In conclusion, patients with overactive with elevated postvoiding residue volumes
      showed increased maximum bladder capacity, but detrusor over-activity was not
      more prevalent in these women compared with women with normal postvoiding residue
      volumes.

PMID- 29379663
TI  - Depression and anxiety disorder in hyperemesis gravidarum: A prospective case
      control study.
AB  - Objective: To assess the anxiety and depression status of women with hyperemesis
      gravidarum (HG); the risk factors for developing both depression and anxiety in
      women with HG were evaluated. Materials and Methods: A total of 200 women, 100
      diagnosed as having HG before the 20th week of gestation at a tertiary referral
      center and 100 gestational-age-matched controls were enrolled. The socio
      demographic data and the depression and anxiety scores, as assessed using the
      Beck depression and anxiety inventory were compared between the two groups.
      Results: The median depression and anxiety scores were significantly higher in
      the HG group compared with controls (19.5 vs. 9.0 and 22.0 vs. 10.0). Women with
      HG have the highest relative risks for moderate depression and severe anxiety
      [relative risk (RR): 16.88 and RR: 20.50, respectively]. In the univariate
      analysis, having HG, low education level, low income and poor social
      relationships were significant predictors of depression and having HG. Moreover,
      poor social relationships significantly predicted the presence of anxiety
      disorder. However, having HG and poor social relationships were found as the only
      independent predictors of both depression and anxiety. Patients with HG were 5.5
      and 6.7 times more prone to having depression and anxiety disorder compared with
      controls, respectively. Conclusion: Both depression and anxiety disorder were
      more frequent in women with HG who have weak family and social relationships,
      lower education and income levels. Therefore, the determination of the
      psychological status of women with HG should be an integral part of the
      evaluation.

PMID- 29379664
TI  - Endothelial cell leptin receptors, leptin and interleukin-8 in the pathogenesis
      of preeclampsia: An in-vitro study.
AB  - Objective: Increased leptin hormone and leptin receptor may enhance the
      generation of proinflammatory cytokines by endothelial cells and lead to
      endothelial dysfunction. This study assessed the umbilical cord endothelial
      leptin receptor levels in preeclampsia and investigated the effect of leptin on
      endothelial interleukin-8 (IL-8) production. Materials and Methods: The
      association between IL-8 levels with leptin stimulation was investigated in
      leptin-treated human endothelial cells. Endothelial cell leptin receptor levels
      were evaluated using immunohistochemistry staining, and endothelial IL-8 protein
      expression by Western blot analysis. Data are presented as mean +/- standard
      error of the mean (SEM). Statistical significance was analyzed using Student's t
      test or Mann-Whitney U test and one-way analysis of variance. Results: Leptin
      receptor immunoreactivity increased significantly in umbilical cord venous and
      arterial endothelial cells in normal pregnancy (n=12) compared with preeclampsia
      (n=7) endothelial cells. The corresponding preeclampsia versus control histologic
      scores (mean +/- SEM) were 67.9+/-8.8 vs. 127.6+/-23.1, (p=0.011) for the leptin
      receptor and 55.4+/-8,0 vs. 93.7+/-17.1 (p=0.035), respectively, for the vein
      endothelial cells. Leptin treatment significantly increased IL-8 protein levels
      (control vs. 100 and 1000 ng/mL, p=0.003). Conclusion: The findings of increased
      umbilical cord endothelial leptin receptor levels in preeclampsia and increased
      endothelial IL-8 expression with exposure to higher leptin concentrations may
      indicate the contribution of leptin to endothelial dysfunction and increased
      neutrophil-endothelial interaction, which are significant pathophysiologic
      features of preeclampsia.

PMID- 29379665
TI  - The oxidative/anti-oxidative effects of sevoflurane on reproductive system of
      females: An experimental study.
AB  - Objective: A permanent balance exists between the production and elimination of
      reactive oxygen species in all living organisms. The aim of this study was to
      evaluate the effects of sevoflurane possibly causing an imbalance in the equation
      of reactive oxygen species on the female rat reproductive system. Materials and
      Methods: A total of 30 adult female Wistar-albino rats were placed into an
      anesthesia chamber to administer sevoflurane. Rats were randomly divided into six
      groups, each group consisting of five rats: the control group received 2 L/min O2
      18 min/day for seven days; the first group received 1 minimum alveolar
      concentration (MAC) of sevoflurane and 2 L/min O2 18 min/day for seven days; the
      second group received 1 MAC of sevoflurane and 2 L/min O2 18 min/day for seven
      days with no treatment for the next seven days; the third group received 1 MAC of
      sevoflurane and 2 L/min O2 18 min/day for 14 days; the fourth group received 1
      MAC of sevoflurane and 2 L/min O2 18 min/day for 14 days with no treatment for
      the next seven days; and the fifth group received 1 MAC of sevoflurane and 2
      L/min O2 18 min/day for 14 days with no treatment for the next 14 days. Bilateral
      ovaries were subsequently removed for biochemical analysis of tissue anti
      oxidative enzyme levels. Results: Slight fluctuations were detected in mean
      nitric oxide, prostaglandin E2, prostaglandin F2-alpha, superoxide dismutase,
      glutathione peroxidase, malondialdehyde, alginate dialdehyde, and xanthine
      oxidase levels between the groups; however, the differences were not significant
      (p>0.05). Conclusion: Sevoflurane has no effect on the activity of anti-oxidant
      systems in the rat ovary.

PMID- 29379666
TI  - Could the female-to-male transgender population be donor candidates for uterus
      transplantation?
AB  - Objective: To evaluate the eligibility of female-to-male (FtM) transgender people
      as donor candidates with regard to histologic, surgical, and social aspects.
      Materials and Methods: In this prospective cohort study, 31 FtM transgender
      people underwent standard hysterectomy and bilateral salpingo-oophorectomy for
      gender reassignment upon their request. The pelvic viscera of the transgender
      people was intraoperatively observed and the histology of the removed uteri were
      evaluated for fertility capacity and procurement surgery. A questionnaire was
      administered to explore their attitude towards uterus donation. Results: The mean
      +/- standard deviation age was 28.5+/-5 years. The median duration of
      testosterone supplementation was 2.4 years; therefore, they all had irregular
      menstrual periods during this therapy. None had any previous abdominal surgery or
      additional morbidity. The mean uterine volume was 138+/-48 cm3. No adenomyosis,
      endometriosis, polyps, adhesions or uterine anomalies were either observed or
      reported. Endometrial histology was reported as proliferative (58%), atrophic
      (29%), and secretory (13%) pattern. Of the 31 transgender people, 30 (96.7%) had
      a positive attitude; only one had no opinion at the beginning. After detailed
      information about the procedure was given, 26 (84%) still wanted to volunteer for
      donation, but 4 (12%) changed their opinion to negative (p=0.12, McNemar test).
      Conclusion: The proposal of the FtM transgender population as uterus donor is a
      hypothetical model that has not been experienced before. Nevertheless, our
      experience revealed that the FtM transgender population would be good candidates
      socially, legally, and biologically.

PMID- 29379667
TI  - The efficacy of laparoscopic presacral neurectomy in dysmenorrhea: is it related
      to the amount of excised neural tissue?
AB  - Objective: To assess the correlation between the number of excised neural fibers
      and degree of pain relief following laparoscopic presacral neurectomy (LPSN).
      Materials and Methods: In this before and after study, 20 patients with severe
      midline dysmenorrhea [Visual Analogue Scale (VAS) >80 mm] unresponsive to medical
      therapy were consecutively enrolled. All patients underwent LPSN. The superior
      hypogastric plexus was excised and sent for histologic confirmation. Two
      pathologists counted the number of neural fibers in the surgically removed
      tissue. VAS was used for pain assessment before and 2nd, 3rd, 6th, and 12th
      months after the operations. Results: Out of the initial 20 patients undergoing
      LPSN, eight were excluded from the final analysis due to intraoperative diagnosis
      of endometriosis; therefore, the remaining 12 patients were evaluated. The pain
      scores significantly decreased at each follow-up visit compared with the
      preoperative period (p=0.002). The pathologists, who were blinded, reported the
      median (minimum-maximum) neural fiber count as 46 (20-85) and 47 (18-83). No
      significant correlation was demonstrated between the number of excised neural
      fibers and the amount of pain relief following LPSN. Conclusion: LPSN is an
      effective surgical procedure to control primary dysmenorrhea. Our preliminary
      results revealed that the degree of pain relief in cases of severe midline
      dysmenorrhea was not related to the amount of excised neural tissue in LPSN.

PMID- 29379668
TI  - Sleep quality of endometrial cancer survivors and the effect of treatments.
AB  - Objective: Sleep disorders affect 54.9% of gynaecologic cancer survivors. The
      effect of treatment methods on sleep quality is not clear. This study evaluated
      the sleep quality of survivors of endometrial cancer and compared the effects of
      different treatments on sleep quality. Materials and Methods: Patients were
      categorised as surgery (group 1), surgery + brachytherapy (BRT) (group 2),
      surgery + external beam radiation therapy (EBRT) (group 3), and surgery + EBRT +
      BRT + chemotherapy (group 4). Sleep quality was assessed using the Pittsburgh
      Sleep Quality Index (PSQI) questionnaire. The PSQI was completed by the
      participants before surgery, 1, 3, and 6 months after each treatment was
      completed. The PSQI scores were compared between the different measurement times
      and different study groups. Results: This study enrolled 114 patients with a mean
      age of 58.1+/-11 years. The number of participants in each group was 53 (46.5%),
      14 (12.3%), 12 (10.5%), and 35 (30.7%), respectively. At baseline, 28 (24.6%)
      patients reported poor sleep quality. The mean PSQI score reached the maximum
      level at the second measurement and decreased slightly during follow-up and the
      change in the PSQI score was significant (p=0.001). Group 3 and group 4 had
      significantly higher scores from baseline (p<0.008). At time point 3, the
      differences between the groups were significant. At time point 4, the most
      prominent effect of treatment on sleep quality was observed in patients with
      combined chemo-radiotherapy when compared with the other study groups.
      Conclusion: Most survivors of endometrial cancer are affected by poor sleep
      quality during their treatment. To improve these patients' quality of life, this
      disorder must be considered at each visit and tailored care plans should be
      developed to meet the women's needs. Further studies are needed to evaluate the
      long-term results of sleep quality on patients with endometrial cancer.

PMID- 29379669
TI  - Molar pregnancy in cesarean section scar: A case report.
AB  - Cesarean scar ectopic pregnancies and molar pregnancies are two very rare
      obstetric pathologies. In both cases, serious morbidities are involved that
      require careful management. The coexistence of the two clinical conditions is far
      less common and there are a limited number of cases in the literature. In this
      case report, a 34-year-old patient with previous cesarean section was diagnosed
      as having a molar pregnancy in a cesarean scar through ultrasonography. The
      patient was asymptomatic at that time. Ultrasonography revealed a protruding mass
      at the cesarean section and her human chorionic gonadotropin level was measured
      as 59.705 mIU/mL. Due to the risk of severe bleeding, cesarean section scar
      excision and revision were performed via laparotomy after counselling the
      patient. Removal of all trophoblastic tissue was observed as a result of the
      frozen pathology and the operation was terminated. After the definite pathology
      result came as a complete molar pregnancy, the patient was followed up according
      to molar pregnancy follow-up protocols and cured completely. Despite the
      alternative treatment options (methotrexate application, curettage, uterine
      artery embolization) in such patients, the decision for surgery was made after
      counselling the patient. In this very rare clinical condition, patients should be
      closely monitored and the appropriate treatment option should be applied as soon
      as possible, taking into consideration the bleeding risks of both pathologies.

PMID- 29379670
TI  - Uterine rupture in pregnancy subsequent to hysteroscopic surgery: A case series.
AB  - Uterine rupture during pregnancy is associated with high mortality and morbidity
      rates in both the fetus and the mother. Hysteroscopic surgeries such as
      myomectomy and septum resection are known risk factors for uterine rupture in
      pregnancy following the operation. We present four infertile patients who were
      admitted to Kocaeli Medical Park Hospital between February 2014 and November
      2016. Three of the patients underwent hysteroscopic septum resection without
      complication and one had hysteroscopic myomectomy and a 7-8 mm sized rupture was
      detected. All of the patients became pregnant in less than a year after the
      operations. The first three patients had uterine rupture at 22nd, 38th, and 10th
      week, which is the earliest rupture in the literature. The last patient had an
      uneventful pregnancy and the rupture was observed during cesarean section. A
      short interval between hysteroscopy and pregnancy may increase the risk of
      rupture. It may be possible to become pregnant despite rupture and not have any
      problems during the entire pregnancy.

PMID- 29379671
TI  - Fertility preservation in male patients subjected to chemotherapy; innovative
      approaches for further progress.
AB  - About 4% of male patients with cancer are under the age of 35 years. With the
      current increase in efficacy and safety of therapies, a growing number of young
      adults can achieve long-term survival. In male patients receiving systemic
      chemotherapy and or bone marrow transplantation, a permanent loss of fertility is
      a common adverse effect. The only possibility to preserve the patient's fertility
      is to spare the gametes or gamete-forming cells from the chemotherapeutic effect.
      In adults, this can be achieved by the cryopreservation of spermatozoa with the
      subsequent application of assisted reproductive technology. Sperm
      cryopreservation is currently performed using slow-rate cryopreservation as a
      standard method, in which sperm cells are incubated with a cryoprotective medium
      and slowly subjected to hypothermia in liquid nitrogen (LN) vapor before they are
      placed in LN. Another technique called vitrification relies on the direct
      placement of the cells into LN, after being suspended in a vitrification medium.
      Many studies compared the clinical outcomes of both techniques and revealed
      equivalent results. This paper sheds light on some innovative approaches for
      further progress.

PMID- 29379672
TI  - Series Pneumatic Artificial Muscles (sPAMs) and Application to a Soft Continuum
      Robot.
AB  - We describe a new series pneumatic artificial muscle (sPAM) and its application
      as an actuator for a soft continuum robot. The robot consists of three sPAMs
      arranged radially round a tubular pneumatic backbone. Analogous to tendons, the
      sPAMs exert a tension force on the robot's pneumatic backbone, causing bending
      that is approximately constant curvature. Unlike a traditional tendon driven
      continuum robot, the robot is entirely soft and contains no hard components,
      making it safer for human interaction. Models of both the sPAM and soft continuum
      robot kinematics are presented and experimentally verified. We found a mean
      position accuracy of 5.5 cm for predicting the end-effector position of a 42 cm
      long robot with the kinematic model. Finally, closed-loop control is demonstrated
      using an eye-in-hand visual servo control law which provides a simple interface
      for operation by a human. The soft continuum robot with closed-loop control was
      found to have a step-response rise time and settling time of less than two
      seconds.

PMID- 29379673
TI  - "If You Are Old Enough to Die for Your Country, You Should Be Able to Get a Pinch
      of Snuff": Views of Tobacco 21 Among Appalachian Youth.

PMID- 29379674
TI  - Clinical tolerability of generic versus brand beta blockers in heart failure with
      reduced left ventricular ejection fraction: a retrospective cohort from heart
      failure clinic.
AB  - Background: Beta-blockers have been shown to decrease mortality and morbidity in
      heart failure with reduced ejection fraction (HFrEF) patients. However, the side
      effects are also dose-related, leading to the underdosing. Cost constraint may be
      one of the limitations of appropriate beta-blocker use; this can be improved with
      generic drugs. However, the effects in real life practice have not been
      investigated. Methods and results: This study aimed to compare the efficacy and
      safety of generic and brand beta-blockers in HFrEF patients. We performed a
      retrospective cohort analysis in HFrEF patients who received either generic or
      brand beta-blocker in Chiang Mai Heart Failure Clinic. The primary endpoint was
      the proportion of patients who received at least 50% target dose of beta-blocker
      between generic and brand beta-blockers. Adverse events were secondary endpoints.
      217 patients (119 and 98 patients received generic and brand beta-blocker,
      respectively) were enrolled. There were no differences between groups regarding
      age, gender, etiology of heart failure, New York Heart Association (NYHA)
      functional class, left ventricular ejection fraction (LVEF), rate of receiving
      angiotensin converting enzyme inhibitor (ACEI), angiotensin recepter blocker
      (ARB), or spironolactone. Patients receiving brand beta-blockers had lower
      resting heart rate at baseline (74.9 and 84.2 bpm, p = .001). Rate of achieved
      50% target dose and target daily dose did not differ between groups (40.4 versus
      44.5% and 48.0 versus 55.0%, p > .05, respectively). Rate of side effects was not
      different between groups (32.3 versus 29.5%, p > .05) and the most common side
      effect was hypotension. Conclusion: This study demonstrated that beta-blocker
      tolerability was comparable between brand and generic formulations. Generic or
      brand beta-blockers should be prescribed to HFrEF patients who have no
      contraindications.

PMID- 29379676
TI  - Letter from the Editor.

PMID- 29379677
TI  - Letter from the Editor.

PMID- 29379675
TI  - The Online OurRelationship Program for Relationally Distressed Individuals: A
      Pilot Randomized Controlled Trial.
AB  - Relationship distress has deleterious effects on mental health, physical health,
      and quality of life. Although many couples report relationship distress, one
      barrier to seeking services is that one member of a couple may be too busy or
      refuse to participate. Relationship interventions offered to individuals have
      shown promising efficacy, but, as most are offered in-person, barriers to their
      reach remain. To increase the reach of such interventions, the present pilot
      study examined the efficacy of a fully web-based relationship intervention for
      individuals (OR-I). The program was adapted from the couple version of the
      OurRelationship program (OR-C), which is effective in improving relationship and
      individual functioning (Doss et al., 2016). Results indicated that couples
      randomized to the OR-I program, compared to couples in a waitlist control group,
      saw significant improvement in quality of life (d = 0.69), work functioning (d =
      0.44), and perceived health (d = 0.49) during treatment. Furthermore, gains in
      quality of life and perceived health for the intervention group were maintained
      over short-term follow-up. However, there were no significant improvements in
      relationship functioning or symptoms of depression or anxiety. When comparing the
      efficacy of OR-I and a demographically-matched subsample of OR-C, results showed
      that change in outcomes did not significantly differ by program. Overall, with
      some adaptations, OR-I may be a viable option for individuals seeking
      relationship help. Limitations, potential adaptations, and future directions are
      discussed in-depth.

PMID- 29379678
TI  - Letter from the Editor.

PMID- 29379679
TI  - Letter from the Editor.

PMID- 29379681
TI  - Letter from the Editor.

PMID- 29379680
TI  - Letter from the Editor.

PMID- 29379682
TI  - Species identification by conservation practitioners using online images:
      accuracy and agreement between experts.
AB  - Emerging technologies have led to an increase in species observations being
      recorded via digital images. Such visual records are easily shared, and are often
      uploaded to online communities when help is required to identify or validate
      species. Although this is common practice, little is known about the accuracy of
      species identification from such images. Using online images of newts that are
      native and non-native to the UK, this study asked holders of great crested newt
      (Triturus cristatus) licences (issued by UK authorities to permit surveying for
      this species) to sort these images into groups, and to assign species names to
      those groups. All of these experts identified the native species, but agreement
      among these participants was low, with some being cautious in committing to
      definitive identifications. Individuals' accuracy was also independent of both
      their experience and self-assessed ability. Furthermore, mean accuracy was not
      uniform across species (69-96%). These findings demonstrate the difficulty of
      accurate identification of newts from a single image, and that expert judgements
      are variable, even within the same knowledgeable community. We suggest that
      identification decisions should be made on multiple images and verified by more
      than one expert, which could improve the reliability of species data.

PMID- 29379683
TI  - Breeding and multiple waves of primary molt in common ground doves of coastal
      Sinaloa.
AB  - For adult Common Ground Doves from Sinaloa we demonstrate that the primaries are
      a single molt series, which sometimes feature two (in one case three) waves of
      feather replacement. Such stepwise primary replacement is found in many large
      birds but, at 40 g, this dove is much the smallest species reported to have
      multiple waves of replacement proceeding through its primaries simultaneously.
      Pre-breeding juvenile Common Ground Doves never feature two waves of primary
      replacement. Juveniles usually have more than two adjacent feathers growing
      simultaneously and replace their primaries in about 100 days. In contrast adults,
      which extensively overlap molt and breeding, usually grow just a single primary
      at a time, and require at least 145 days to replace their primaries. Molt arrests
      are thought to drive the generation of new waves of primary replacement in a
      diversity of large birds. For adult Common Ground Doves, we found molt arrests to
      be strongly associated with active crop glands, suggesting that the demands of
      parental care cause arrests in primary replacement in this dove. For those adults
      with two primary molt waves, initiation of an inner wave was most frequently
      observed once the outer wave had reached P10. Thus, unlike reports for large
      birds, Common Ground Doves usually suppress the initiation of a new wave of molt
      starting at P1 when the preceding wave arrests before reaching the distal
      primaries. This assures that relatively fresh inner primaries are not replaced
      redundantly, overcoming a serious flaw in stepwise molting in large birds
      (Rohwer, 1999).

PMID- 29379684
TI  - Characterization of sympatric Platanthera bifolia and Platanthera chlorantha
      (Orchidaceae) populations with intermediate plants.
AB  - Platanthera bifolia and P. chlorantha are terrestrial and rewarding orchids with
      a wide Eurasian distribution. Although genetically closely related, they exhibit
      significant morphological, phenological and ecological differences that maintain
      reproductive isolation between the species. However, where both species co-occur,
      individuals with intermediate phenotypic traits, often considered as hybrids, are
      frequently observed. Here, we combined neutral genetic markers (AFLPs),
      morphometrics and floral scent analysis (GC-MS) to investigate two mixed
      Platanthera populations where morphologically intermediate plants were found.
      Self-pollination experiments revealed a low level of autogamy and artificial
      crossings combined with assessments of fruit set and seed viability, showed
      compatibility between the two species. The results of the genetic analyses showed
      that morphologically intermediate plants had similar genetic patterns as the P.
      bifolia group. These results are corroborated also by floral scent analyses,
      which confirmed a strong similarity in floral scent composition between
      intermediate morphotypes and P. bifolia. Therefore, this study provided a much
      more detailed picture of the genetic structure of a sympatric zone between two
      closely allied species and supports the hypothesis that intermediate morphotypes
      in sympatry could reflect an adaptive evolution in response to local pollinator
      mediated selection.

PMID- 29379685
TI  - Molecular phylogenetics of swimming crabs (Portunoidea Rafinesque, 1815) supports
      a revised family-level classification and suggests a single derived origin of
      symbiotic taxa.
AB  - Portunoidea is a diverse lineage of ecologically and economically important
      marine crabs comprising 8 families and 14 subfamilies. Closely related portunid
      subfamilies Caphyrinae and Thalamitinae constitute some of this group's greatest
      morphological and taxonomic diversity, and are the only known lineages to include
      symbiotic taxa. Emergence of symbiosis in decapods remains poorly studied and
      portunoid crabs provide an interesting, but often overlooked example. Yet the
      paucity of molecular phylogenetic data available for Portunoidea makes it
      challenging to investigate the evolution and systematics of the group.
      Phylogenetic analyses, though limited, suggest that many putative portunoid taxa
      are para- or polyphyletic. Here I augment existing molecular data-significantly
      increasing taxon sampling of Caphyrinae, Thalamitinae, and several disparate
      portunoid lineages-to investigate the phylogenetic origin of symbiosis within
      Portunoidea and reevaluate higher- and lower-level portunoid classifications.
      Phylogenetic analyses were carried out on sequences of H3, 28S rRNA, 16S rRNA,
      and CO1 for up to 168 portunoid taxa; this included, for the first time,
      molecular data from the genera Atoportunus, Brusinia, Caphyra, Coelocarcinus,
      Gonioinfradens, Raymanninus, and Thalamonyx. Results support the placement of all
      symbiotic taxa (Caphyra, Lissocarcinus, and two Thalamita) in a single clade
      derived within the thalamitine genus Thalamita. Caphyrina Paulson, 1875, nom.
      trans. is recognized here as a subtribe within the subfamily Thalamitinae.
      Results also support the following taxonomic actions: Cronius is reclassified as
      a thalamitine genus; Thalamonyx is reestablished as a valid genus; Goniosupradens
      is raised to the generic rank; and three new genera (Zygita gen. nov., Thranita
      gen. nov., and Trierarchus gen. nov.) are described to accommodate some Thalamita
      s.l. taxa rendered paraphyletic by Caphyrina. A new diagnosis of Thalamitinae is
      provided. Results also support a more conservative classification of Portunoidea
      comprising three instead of eight extant families: Geryonidae (Geryonidae +
      Ovalipidae; new diagnosis provided), Carcinidae (Carcinidae + Pirimelidae +
      Polybiidae + Thiidae + Coelocarcinus; new diagnosis provided) and Portunidae.
      Finally, 16s rRNA data suggests family Brusiniidae might not be a portunoid
      lineage.

PMID- 29379686
TI  - Genomic signal processing for DNA sequence clustering.
AB  - Genomic signal processing (GSP) methods which convert DNA data to numerical
      values have recently been proposed, which would offer the opportunity of
      employing existing digital signal processing methods for genomic data. One of the
      most used methods for exploring data is cluster analysis which refers to the
      unsupervised classification of patterns in data. In this paper, we propose a
      novel approach for performing cluster analysis of DNA sequences that is based on
      the use of GSP methods and the K-means algorithm. We also propose a visualization
      method that facilitates the easy inspection and analysis of the results and
      possible hidden behaviors. Our results support the feasibility of employing the
      proposed method to find and easily visualize interesting features of sets of DNA
      data.

PMID- 29379687
TI  - EU protected area network did not prevent a country wide population decline in a
      threatened grassland bird.
AB  - Background: Few studies have assessed the effectiveness of the Protected Area
      networks on the conservation status of target species. Here, we assess the
      effectiveness of the Portuguese Natura 2000 (the European Union network of
      protected areas) in maintaining a species included in the Annex I of the Bird
      Directive, namely the population of a priority farmland bird, the little bustard
      Tetrax tetrax. Methods: We measured the effectiveness of the Natura 2000 by
      comparing population trends across time (2003-2006 and 2016) in 51 areas, 21 of
      which within 12 Special Protection Areas (SPA) that were mostly designated for
      farmland bird conservation and another 30 areas without EU protection. Results:
      Overall, the national population is estimated to have declined 49% over the last
      10-14 years. This loss was found to be proportionally larger outside SPA (64%
      decline) compared to losses within SPA (25% decline). However, the absolute male
      density decline was significantly larger within SPA . Discussion: In spite of
      holding higher population densities and having prevented habitat loss, we
      conclude that Natura 2000 was not effective in buffering against the overall
      bustard population decline. Results show that the mere designation of SPA in
      farmland is not enough to secure species populations and has to be combined with
      agricultural policies and investment to maintain not only habitat availability
      but also habitat quality.

PMID- 29379688
TI  - Are pumas subordinate carnivores, and does it matter?
AB  - Background: Interspecific competition affects species fitness, community
      assemblages and structure, and the geographic distributions of species.
      Established dominance hierarchies among species mitigate the need for fighting
      and contribute to the realized niche for subordinate species. This is especially
      important for apex predators, many of which simultaneous contend with the costs
      of competition with more dominant species and the costs associated with human
      hunting and lethal management. Methods: Pumas are a widespread solitary felid
      heavily regulated through hunting to reduce conflicts with livestock and people.
      Across their range, pumas overlap with six apex predators (gray wolf, grizzly
      bear, American black bear, jaguar, coyote, maned wolf), two of which (gray wolf,
      grizzly bear) are currently expanding in North America following recovery
      efforts. We conducted a literature search to assess whether pumas were
      subordinate or dominant with sympatric apex predators, as well as with three
      felid mesocarnivores with similar ecology (ocelot, bobcat, Canada lynx). We also
      conducted an analysis of the spatial distributions of pumas and their dominant
      sympatric competitors to estimate in what part of their range, pumas are dominant
      versus subordinate. Results: We used 64 sources to assess dominance among pumas
      and other apex predators, and 13 sources to assess their relationships with felid
      mesocarnivores. Evidence suggested that wolves, grizzly bears, black bears, and
      jaguars are dominant over pumas, but that pumas are dominant over coyotes and
      maned wolves. Evidence suggested that pumas are also dominant over all three
      felid mesocarnivores with which they share range. More broadly, pumas are
      subordinate to at least one other apex carnivore in 10,799,252 (47.5%) of their
      22,735,268 km2 range across North and South America. Discussion: Subordinate
      pumas change their habitat use, suffer displacement at food sources, likely
      experience increased energetic demands from harassment, exhibit increased
      starvation, and are sometimes directly killed in competitive interactions with
      dominant competitors. Nevertheless, we lack research clearly linking the costs of
      competition to puma fitness. Further, we lack research that assesses the
      influence of human effects simultaneous with the negative effects of competition
      with other sympatric carnivores. Until the time that we understand whether
      competitive effects are additive with human management, or even potentially
      synergistic, we encourage caution among managers responsible for determining
      harvest limits for pumas and other subordinate, apex carnivores in areas where
      they are sympatric with dominant species. This may be especially important
      information for managers working in regions where wolves and brown bears are
      recolonizing and recovering, and historic competition scenarios among multiple
      apex predators are being realized.

PMID- 29379689
TI  - Molecular and serological dynamics of Chlamydia pecorum infection in a
      longitudinal study of prime lamb production.
AB  - Background: Chlamydia pecorum is a globally significant livestock pathogen
      causing pathology and production losses. The on-farm infection and serological
      dynamics and the relevance of existing diagnostic tools for diagnosing C. pecorum
      in livestock remains poorly characterized. In this study, we characterized the
      antigen and antibody dynamics of this pathogen in a longitudinal study of prime
      lamb production, utilizing the infection focused C. pecorum-specific 16S rRNA
      qPCR assay and serology based chlamydial Complement fixation Test (CFT). Methods:
      The study consisted of 76 Border Leicester mixed sex lambs (39 females and 37
      males) that were sampled bimonthly from 2-10 months of age in a commercial farm
      operating in Central NSW, Australia. Blood/plasma was analysed for CFT
      antibodies, and swabs from conjunctival, rectal and vaginal sites were analysed
      for C. pecorum shedding using qPCR. We assessed the temporal and overall dynamics
      of C. pecorum in lambs, including detailed description and comparison of qPCR and
      CFT, the timing of first detection by either diagnostic method, the lag between
      infection and antibody response; and the distribution of qPCR load and CFT
      antibody titre over time. Results: Over the study period, C. pecorum was highly
      prevalent (71.0% by qPCR, 92.1% by CFT, 96.0% by both), with 21.1% (16/76) lambs
      shedding >=1, 000 qPCR copies/ul (denoted as high shedders). C. pecorum shedding
      (as evidence of infection) were first observed at two months of age (14.4%) with
      a significant peak of infection occurring at six months of age (34.2%), whereas
      seroconversions peaked at eight months of age (81.5%). 52.6% of C. pecorum qPCR
      and CFT positive lambs became qPCR negative by 10 months of age, indicating
      clearance of chlamydial infection. Although CFT is utilised for on-farm detection
      of active infection, we confirm that it lagged behind qPCR detection (average lag
      1.7 +/- 2.1 months) and that the proportion of qPCR positives simultaneously
      identified by CFT was low with 2/11 (18.1%), 0/13, 17/25 (68.0%), 5/7 (71.4%) and
      1/10 (10.0%) concurrent seroconversions occurring at two, four, six, eight and 10
      months of age, respectively. Discussion: This work reveals rapid rates of C.
      pecorum infection and widespread exposure during lamb production. The comparison
      of molecular and serological diagnostic agreement longitudinally, supports the
      use of qPCR as an important ancillary tool for the detection of active infections
      in conjunction with chlamydial CFT for routine veterinary diagnostics.
      Development of rapid Point-of-Care (POC) tools for diagnosing active infection
      would be valuable for producers and veterinarians.

PMID- 29379691
TI  - Isolation and culture of primary adult skin fibroblasts from the Asian elephant
      (Elephas maximus).
AB  - Background: Primary cultures from Asian elephants (Elephas maximus) allow
      scientists to obtain representative cells that have conserved most of their
      original characteristics, function, physiology and biochemistry. This technique
      has thus gained significant importance as a foundation for further cellular, cell
      biology and molecular research. Therefore, the aim of this study was to describe
      conditions for the successful establishment of primary adult fibroblasts from
      Asian elephant carcasses. Methods: Ear tissue sample collection from Asian
      elephant carcasses and our recommendations are given. We describe here a simple
      modified protocol for successful isolation and maintenance of primary adult
      fibroblasts from elephant ear skin. Ear samples from each individual (five 3 * 3
      cm2 pieces) were brought to the laboratory within 3 h after collection, kept in
      transportation medium at 0-4  degrees C. The ear tissues were prepared by a
      combination of 10% collagenase type II digestion procedure together with a simple
      explant procedure. Primary fibroblasts were cultured at 37  degrees C in
      Dulbecco's modified Eagle's medium (DMEM) with 20% fetal calf serum (FCS) in a
      humidified atmosphere containing 5% CO2. After the third passage, fibroblasts
      were routinely trypsinized with 0.25% trypsin/EDTA and cultured in DMEM with 10%
      FCS at 37  degrees C and 5% CO2. Traditional cell counting method was used to
      measure cell viability and growth curve. Long-term storage of cells used freezing
      medium consisting of 40% FCS (v/v). Results: We explored the most suitable
      conditions during sample collection (post-mortem storage time and sample storage
      temperature), which is the most important step in determining primary outgrowth.
      Our study successfully established and cultured primary adult skin fibroblasts
      obtained from post-mortem E. maximus ear skin tissues from six carcasses, with a
      success rate of around 83.3%. Outgrowth could be seen 4-12 days after
      explantation, and epithelial-like cells were found after 4-7 days of culture,
      while fibroblasts appeared at around day 7-10. The fibroblasts had viability and
      post-freezing recovery rates of around 97.3 +/- 4.3% and 95.5 +/- 7.3%,
      respectively, and doubling time was about 25 h (passage 6). Discussion: To our
      knowledge, this report is the first to describe primary cell cultures derived
      from adult Asian elephant skin. Future studies should benefit from the
      information and useful suggestions herein, which may be used as a standard method
      for establishing primary skin fibroblast cultures in future experiments.

PMID- 29379692
TI  - Historical baselines of coral cover on tropical reefs as estimated by expert
      opinion.
AB  - Coral reefs are important habitats that represent global marine biodiversity
      hotspots and provide important benefits to people in many tropical regions.
      However, coral reefs are becoming increasingly threatened by climate change,
      overfishing, habitat destruction, and pollution. Historical baselines of coral
      cover are important to understand how much coral cover has been lost, e.g., to
      avoid the 'shifting baseline syndrome'. There are few quantitative observations
      of coral reef cover prior to the industrial revolution, and therefore baselines
      of coral reef cover are difficult to estimate. Here, we use expert and ocean-user
      opinion surveys to estimate baselines of global coral reef cover. The overall
      mean estimated baseline coral cover was 59% (+/-19% standard deviation), compared
      to an average of 58% (+/-18% standard deviation) estimated by professional
      scientists. We did not find evidence of the shifting baseline syndrome, whereby
      respondents who first observed coral reefs more recently report lower estimates
      of baseline coral cover. These estimates of historical coral reef baseline cover
      are important for scientists, policy makers, and managers to understand the
      extent to which coral reefs have become depleted and to set appropriate recovery
      targets.

PMID- 29379690
TI  - Tissue material properties and computational modelling of the human tibiofemoral
      joint: a critical review.
AB  - Understanding how structural and functional alterations of individual tissues
      impact on whole-joint function is challenging, particularly in humans where
      direct invasive experimentation is difficult. Finite element (FE) computational
      models produce quantitative predictions of the mechanical and physiological
      behaviour of multiple tissues simultaneously, thereby providing a means to study
      changes that occur through healthy ageing and disease such as osteoarthritis
      (OA). As a result, significant research investment has been placed in developing
      such models of the human knee. Previous work has highlighted that model
      predictions are highly sensitive to the various inputs used to build them,
      particularly the mathematical definition of material properties of biological
      tissues. The goal of this systematic review is two-fold. First, we provide a
      comprehensive summation and evaluation of existing linear elastic material
      property data for human tibiofemoral joint tissues, tabulating numerical values
      as a reference resource for future studies. Second, we review efforts to model
      tibiofemoral joint mechanical behaviour through FE modelling with particular
      focus on how studies have sourced tissue material properties. The last decade has
      seen a renaissance in material testing fuelled by development of a variety of new
      engineering techniques that allow the mechanical behaviour of both soft and hard
      tissues to be characterised at a spectrum of scales from nano- to bulk tissue
      level. As a result, there now exists an extremely broad range of published values
      for human tibiofemoral joint tissues. However, our systematic review highlights
      gaps and ambiguities that mean quantitative understanding of how tissue material
      properties alter with age and OA is limited. It is therefore currently
      challenging to construct FE models of the knee that are truly representative of a
      specific age or disease-state. Consequently, recent tibiofemoral joint FE models
      have been highly generic in terms of material properties even relying on non
      human data from multiple species. We highlight this by critically evaluating
      current ability to quantitatively compare and model (1) young and old and (2)
      healthy and OA human tibiofemoral joints. We suggest that future research into
      both healthy and diseased knee function will benefit greatly from a subject- or
      cohort-specific approach in which FE models are constructed using material
      properties, medical imagery and loading data from cohorts with consistent
      demographics and/or disease states.

PMID- 29379693
TI  - Do patients with chronic unilateral orofacial pain due to a temporomandibular
      disorder show increased attending to somatosensory input at the painful side of
      the jaw?
AB  - Background: Patients with chronic orofacial pain due to temporomandibular
      disorders (TMD) display alterations in somatosensory processing at the jaw, such
      as amplified perception of tactile stimuli, but the underlying mechanisms remain
      unclear. This study investigated one possible explanation, namely hypervigilance,
      and tested if TMD patients with unilateral pain showed increased attending to
      somatosensory input at the painful side of the jaw. Methods: TMD patients with
      chronic unilateral orofacial pain (n = 20) and matched healthy volunteers (n =
      20) performed a temporal order judgment (TOJ) task indicated which one of two
      tactile stimuli, presented on each side of the jaw, they had perceived first. TOJ
      methodology allows examining spatial bias in somatosensory processing speed.
      Furthermore, after each block of trials, the participants rated the perceived
      intensity of tactile stimuli separately for both sides of the jaw. Finally,
      questionnaires assessing pain catastrophizing, fear-avoidance beliefs, and pain
      vigilance, were completed. Results: TMD patients tended to perceive tactile
      stimuli at the painful jaw side as occurring earlier in time than stimuli at the
      non-painful side but this effect did not reach conventional levels of
      significance (p = .07). In the control group, tactile stimuli were perceived as
      occurring simultaneously. Secondary analyses indicated that the magnitude of
      spatial bias in the TMD group is positively associated with the extent of fear
      avoidance beliefs. Overall, intensity ratings of tactile stimuli were
      significantly higher in the TMD group than in the control group, but there was no
      significant difference between the painful and non-painful jaw side in the TMD
      patients. Discussion: The hypothesis that TMD patients with chronic unilateral
      orofacial pain preferentially attend to somatosensory information at the painful
      side of the jaw was not statistically supported, although lack of power could not
      be ruled out as a reason for this. The findings are discussed within recent
      theories of pain-related attention.

PMID- 29379694
TI  - A robust AFM-based method for locally measuring the elasticity of samples.
AB  - Investigation of the local sample elasticity is of high importance in many
      scientific domains. In 2014, Herruzo et al. published a new method based on
      frequency-modulation atomic force microscopy to locally determine the elasticity
      of samples (Nat. Commun.2014, 5, 3126). This method gives evidence for the
      linearity of the relation between the frequency shift of the cantilever first
      flexural mode Deltaf1 and the square of the frequency shift of the second
      flexural mode Deltaf22. In the present work, we showed that a similar linear
      relation exists when measuring in contact mode with a certain load FN and propose
      a new method for determining the elastic modulus of samples from this relation.
      The measurements were performed in non-dry air at ambient temperature on three
      different polymers (polystyrene, polypropylene and linear low-density
      polyethylene) and a self-assembled monolayer of 1H,1H,2H,2H
      perfluorodecyltrichlorosilane (FDTS) on a silicon oxide substrate perforated with
      circular holes prepared by polymer blend lithography. For all samples the
      relation was evidenced by recording Deltaf1, Deltaf2 and FN as a function of the
      Z-displacement curves of the piezoelectric scanner. The occurence of a plastic
      deformation followed by an elastic deformation is shown and explained. The
      necessary load FN for measuring in the elastic domain was assessed for each
      sample, used for mapping the frequency shifts Deltaf1 and Deltaf2 and for
      determining the elastic modulus from Deltaf22/Deltaf1. The method was used to
      give an estimate of the Young's modulus of the FDTS thin film.

PMID- 29379696
TI  - Advances in nanocarbon composite materials.

PMID- 29379695
TI  - Study of the vertically aligned in-plane switching liquid crystal mode in
      microscale periodic electric fields.
AB  - The ongoing interest in fast liquid crystal (LC) modes stimulated by display
      technology and new applications has motivated us to study in detail the in-plane
      switching (IPS) vertically aligned (VA) mode. We have studied how the decrease of
      the period of the interdigitated electrodes (down to sub-micrometer scale)
      influences the switching speed, especially the LC relaxation to the initial
      homeotropic state. We have found that there are two types of the relaxation: a
      fast relaxation caused by the surface LC sub-layer deformed in the vicinity of
      the electrodes and the slower relaxation of the bulk LC. The speed of the fast
      (surface) mode is defined by half of a period of the electrode grating, while the
      relaxation time of the bulk depends on the LC layer thickness and the length of
      the driving electric pulses. Thus, the use of the surface mode and the reduction
      of the electrode grating period can result in significant increase of switching
      speed compared to the traditional LC modes, where the bulk relaxation dominates
      in electrooptical response. We have studied thoroughly the conditions defining
      the surface mode applicability. The numerical simulations are in good agreement
      with experimental measurements.

PMID- 29379697
TI  - Gas-sensing behaviour of ZnO/diamond nanostructures.
AB  - Microstructured single- and double-layered sensor devices based on p-type
      hydrogen-terminated nanocrystalline diamond (NCD) films and/or n-type ZnO
      nanorods (NRs) have been obtained via a facile microwave-plasma-enhanced chemical
      vapour deposition process or a hydrothermal growth procedure. The morphology and
      crystal structure of the synthesized materials was analysed with scanning
      electron microscopy, X-ray diffraction measurements and Raman spectroscopy. The
      gas sensing properties of the sensors based on i) NCD films, ii) ZnO nanorods,
      and iii) hybrid ZnO NRs/NCD structures were evaluated with respect to oxidizing
      (i.e., NO2, CO2) and reducing (i.e., NH3) gases at 150  degrees C. The hybrid ZnO
      NRs/NCD sensor showed a remarkably enhanced NO2 response compared to the ZnO NRs
      sensor. Further, inspired by this special hybrid structure, the simulation of
      interaction between the gas molecules (NO2 and CO2) and hybrid ZnO NRs/NCD sensor
      was studied using DFT calculations.

PMID- 29379699
TI  - Nematic liquid crystal alignment on subwavelength metal gratings.
AB  - We have studied the alignment of a nematic liquid crystal (LC) material on
      aluminum subwavelength nanogratings as a function of the period, p, and the slit
      width to period ratio, w/p. A method, based on Fourier analysis of the
      transmittance spectra of the LC grating system, has been applied. We show that
      the gratings provide stable planar alignment only for shorter periods and
      narrower slits (p < 400 nm, w/p < 2/3). As these parameters increase, the
      homogeneous surface alignment changes to domains with different tilt angles or to
      spatially modulated alignment. We have also obtained a 90 degrees  twisted LC
      director distribution, implying sufficiently strong azimuthal LC anchoring at the
      grating surface.

PMID- 29379698
TI  - Review on optofluidic microreactors for artificial photosynthesis.
AB  - Artificial photosynthesis (APS) mimics natural photosynthesis (NPS) to store
      solar energy in chemical compounds for applications such as water splitting, CO2
      fixation and coenzyme regeneration. NPS is naturally an optofluidic system since
      the cells (typical size 10 to 100 um) of green plants, algae, and cyanobacteria
      enable light capture, biochemical and enzymatic reactions and the related
      material transport in a microscale, aqueous environment. The long history of
      evolution has equipped NPS with the remarkable merits of a large surface-area-to
      volume ratio, fast small molecule diffusion and precise control of mass transfer.
      APS is expected to share many of the same advantages of NPS and could even
      provide more functionality if optofluidic technology is introduced. Recently,
      many studies have reported on optofluidic APS systems, but there is still a lack
      of an in-depth review. This article will start with a brief introduction of the
      physical mechanisms and will then review recent progresses in water splitting,
      CO2 fixation and coenzyme regeneration in optofluidic APS systems, followed by
      discussions on pending problems for real applications.

PMID- 29379700
TI  - Transition from silicene monolayer to thin Si films on Ag(111): comparison
      between experimental data and Monte Carlo simulation.
AB  - Scanning tunneling microscopy (STM), Auger electron spectroscopy (AES) and low
      energy electron diffraction have been used to follow the growth of Si films on
      Ag(111) at various temperatures. Using a simple growth model, we have simulated
      the distribution of film thickness as a function of coverage during evaporation,
      for the different temperatures. In the temperature regime where multilayer
      silicene has been claimed to form (470-500 K), a good agreement is found with AES
      intensity variations and STM measurements within a Ag surfactant mediated growth,
      whereas a model with multilayer silicene growth fails to reproduce the AES
      measurements.

PMID- 29379701
TI  - Response under low-energy electron irradiation of a thin film of a potential
      copper precursor for focused electron beam induced deposition (FEBID).
AB  - Background: Focused electron beam induced deposition (FEBID) allows for the
      deposition of free standing material within nanometre sizes. The improvement of
      the technique needs a combination of new precursors and optimized irradiation
      strategies to achieve a controlled fragmentation of the precursor for leaving
      deposited material of desired composition. Here a new class of copper precursors
      is studied following an approach that probes some surface processes involved in
      the fragmentation of precursors. We use complexes of copper(II) with amines and
      perfluorinated carboxylate ligands that are solid and stable under ambient
      conditions. They are directly deposited on the surface for studying the
      fragmentation with surface science tools. Results: Infrared spectroscopy and high
      resolution electron energy loss spectroscopy (HREELS) are combined to show that
      the precursor is able to spontaneously lose amine ligands under vacuum. This loss
      can be enhanced by mild heating. The combination of mass spectrometry and low
      energy electron irradiation (0-15 eV) shows that full amine ligands can be
      released upon irradiation, and that fragmentation of the perfluorinated ligands
      is induced by electrons of energy as low as 1.5 eV. Finally, the cross section
      for this process is estimated from the temporal evolution in the experiments on
      electron-stimulated desorption (ESD). Conclusion: The release of full ligands
      under high vacuum and by electron irradiation, and the cross section measured
      here for ligands fragmentation allow one to envisage the use of the two
      precursors for FEBID studies.

PMID- 29379702
TI  - A Neonate with an Unusual Midline Defect and Cardiovascular Anomaly.
AB  - We present a female neonate with a sternal cleft (SC) and additional aortic
      aneurysm who presented with respiratory failure. Stabilization of the SC was
      achieved by using the xyphoid process as an autologous graft bridging the upper
      part of the SC. We conclude that a step-wise correction of the SC with the use of
      an autologous graft may improve respiratory function, and should be considered
      when complete surgical correction is not feasible.

PMID- 29379703
TI  - Clinical features of three patients with paradoxical immune reconstitution
      inflammatory syndrome associated with Talaromyces marneffei infection.
AB  - Talaromyces marneffei infection is a major cause of death in HIV-infected
      individuals in South and Southeast Asia. Talaromycosis immune reconstitution
      inflammatory syndrome has not been well described. Here we report the clinical
      features, management, and outcomes of three HIV-infected patients with
      talaromycosis-associated paradoxical immune reconstitution inflammatory syndrome
      in Ho Chi Minh City, Vietnam.

PMID- 29379704
TI  - Paradoxical respiratory failure due to cryptococcal pneumonia after amphotericin
      B treatment for HIV-associated cryptococcal meningitis.
AB  - We present a 27-year-old lady with HIV-1 infection who died due to rapidly
      worsening respiratory failure one day after commencing amphotericin B
      deoxycholate therapy for cryptococcal meningitis. Chest x-ray appearances were
      consistent with pneumocystis pneumonia but post mortem examination showed
      evidence of severe necrotizing cryptococcal pneumonia. Cryptococcal pneumonia is
      an underrecognized condition and should be considered in the differential of
      patients with HIV-1 infection and low CD4 count who develop respiratory symptoms.

PMID- 29379705
TI  - The important role of co-infections in patients with AIDS and progressive
      disseminated histoplasmosis (PDH): A cohort from Colombia.
AB  - A total of 23/45 (51%) patients with AIDS and histoplasmosis from Medellin,
      Colombia had other infections. Tuberculosis was the most common (n = 16/23, 70%).
      Pneumocystosis and cryptococcosis were found in three patients each (13%),
      bacterial infection and cytomegalovirus occurred each in two patients (9%) while
      toxoplasmosis, herpes virus and esophageal candidiasis were recorded in one
      patient each (4%). Of all co-infected patients, 18/23 (78%) had one, four (17%)
      had two and one (4%) had three additional opportunistic infections.

PMID- 29379706
TI  - Histoplasmosis: An oral malignancy-like clinical picture.
AB  - HIV-associated histoplasmosis is mainly misdiagnosed for granulomatous diseases,
      such as tuberculosis. Nonetheless, malignancy-like lesions have been reported
      sporadically in HIV-infected patients. Although the main reported lesions are
      erosive or ulcerated, here a rare case of oral tumor is reported. This case
      raises the awareness of this presentation, and the importance of accurate
      identification in the laboratory. Performing systematic specific stains for
      fungal elements and culture on tissue samples ensures accurate differential
      diagnosis.

PMID- 29379707
TI  - Arthroscopic Coracohumeral Ligament Release for Patients With Frozen Shoulder.
AB  - Arthroscopic pancapsular release has been recommended for recalcitrant frozen
      shoulder, but regaining range of motion has not been sufficient compared with the
      unaffected side. There is no consensus about the reasons for these remaining
      restrictions in range of motion, but residual capsular or connective tissue must
      be considered a candidate. A thickened coracohumeral ligament at the rotator
      interval has been reported as one of the most specific manifestations of frozen
      shoulder. It covers wider portions of the subscapularis tendon, supraspinatus
      tendon, and infraspinatus tendon than previously reported. We describe an
      arthroscopic surgical technique for the release of the entire coracohumeral
      ligament including the subscapularis and supraspinatus portions and the release
      of the inferior and posterior parts of the glenohumeral ligament using the 7
      o'clock portal. These procedures are essential and reliable methods to release
      the entire joint capsule to regain full range of motion for frozen shoulder.

PMID- 29379708
TI  - An Arthroscopic Knotless Technique for Anatomical Restoration of the Rotator Cuff
      and Superior Capsule: The Double-Layer Cinch Bridge.
AB  - Rotator cuff repairs are the most common procedures in shoulder surgery, but
      still show long-term retear rates of up to 70%. Nonanatomic reconstruction is one
      possible cause of repair failure. The rotator cuff histologically consists of 5
      separate layers of which 2 are macroscopically identifiable: the superior or
      tendinous layer and the inferior or capsule-ligamentous layer. In case of rotator
      cuff tears, these layers are often retracted to different degrees. The
      intraoperative detectable prevalence of rotator cuff delamination reaches up to
      85%. Anatomical rotator cuff repair, which also includes restoration of the
      layered structure, could re-establish native tendon morphology and thus
      potentially decreases retear rates. The use of a knotless construct to avoid cuff
      strangulation and maintaining tendon perfusion could further decrease the risk of
      repair failure. Double-layer reconstructions are challenging and time consuming
      because each layer needs to be penetrated separately. Only few studies reported
      about double-layer reconstruction of the posterosuperior rotator cuff. This
      Technical Note is the first to present an arthroscopic knotless transosseous
      equivalent double-layer repair technique.

PMID- 29379709
TI  - Diagnostic Evaluation of the Knee in the Office Setting Using Small-Bore Needle
      Arthroscopy.
AB  - Arthroscopy is currently the gold standard for diagnosing intra-articular knee
      pathology. Magnetic resonance imaging (MRI) can be a clinical adjunct for
      diagnosis; however, it is not without its shortcomings. Although highly accurate,
      even advanced imaging misdiagnoses the condition in 1 in 14 patients with regard
      to anterior cruciate ligament pathology. Previous studies have indicated that MRI
      fails to identify meniscal pathology when one exists in 1 of every 10 cases, and
      diagnoses pathology when pathology truly does not exist in 1 of every 5 patients.
      In-office arthroscopy offers an alternative to formal diagnostic arthroscopy,
      with reduced cost and risk of complications. This is a technique article that
      discusses the use of small-bore needle arthroscopy in the office setting.

PMID- 29379710
TI  - Laparoscopic Treatment of Pubic Symphysis Instability With Anchors and Tape
      Suture.
AB  - Patients with pubic symphysis instability who had failed nonoperative treatments
      may benefit from surgical repair. This disease process is rare, most commonly
      seen in postpartum women and athletes, and its surgical treatment is invasive and
      nonphysiological. Currently described surgical interventions, although limited,
      include plating, which provides an overly rigid construct with the risk of
      failure and possibly poor long-term outcomes particularly in athletes, and
      treatments such as curettage, more commonly used in the treatment of osteitis
      pubis. An emerging option is minimally invasive laparoscopic fixation using
      knotless anchors with a tape suture in a crisscross configuration. This possibly
      allows more physiological movement of the pubic symphysis in a less invasive
      manner. A detailed technical description and discussion of the technique are
      provided.

PMID- 29379711
TI  - Diversity and prevalence of hemoparasites of wading birds in southern Florida,
      USA.
AB  - Relatively few studies on hemoparasites have been conducted on wading birds in
      the families Ardeidae and Threskiornithidae (order Pelecaniformes), especially in
      the United States. In this study, we obtained baseline data on the prevalence and
      genetic diversity of haemosporidian parasites in wading birds opportunistically
      sampled from southern Florida, USA. We detected blood parasites in White Ibis
      (Eudocimus albus), Glossy Ibis (Plegadis falcinellus), Green Heron (Butorides
      virescens), and Roseate Spoonbill (Platalea ajaja) with several novel host
      parasite relationships. Infected birds had low parasitemias (average 0.77%, range
      0-4%) suggesting that infections were chronic. Despite the low sample sizes for
      several of our sampled species, these data highlight the diversity of parasites
      in this understudied group of birds and suggest that additional studies are
      needed to investigate the potential impacts of these parasites on their health,
      especially since southern Florida is becoming increasingly urbanized which can
      alter parasite transmission or host susceptibility.

PMID- 29379712
TI  - Ectoparasitic copepod infestation on a wild population of Neotropical catfish
      Sciades herzbergii Bloch, 1794: Histological evidences of lesions on host.
AB  - We analyzed the infestation of the attached copepod species Lepeophtheirus sp on
      a wild population of Sciades herzbergii. The infestation and occurrence of
      attached copepods were related to body size, maturity and sex of host and the
      presence of lesions on fish skin were described. In 61 fish specimens (37 males
      and 24 females), total of 218 ectoparasitic copepods, including 204 mature and 14
      immature stages were found. Copepods were attached to different regions of fish
      body without any regular pattern. The prevalence of infestation was 80.3% and
      intensity between 1 and 15 copepods/fish. No significant differences were found
      between sex or maturity and the presence of attached Lepeophtheirus sp. However,
      a contingency table including both sex and maturity status, and the total number
      of attached copepod per combined category showed a significant association. A
      positive correlation was found between body length of fish and intensity of
      infestation. Similarly, when comparing the infested fish according to group size,
      we found more copepods on larger individual. Attached copepods were associated
      with the presence of lesions visible to the naked eye. Histological analyses
      showed changes in cell architecture when sections of copepod-free tissues and
      attached copepods were compared.

PMID- 29379713
TI  - Meerkats (Suricata suricatta), a new definitive host of the canid nematode
      Angiostrongylus vasorum.
AB  - Angiostronglyus vasorum is a cardiopulmonary nematode infecting mainly canids
      such as dogs (Canis familiaris) and foxes (Vulpes vulpes). Natural infections
      have also been reported in mustelids and red pandas (Ailurus fulgens fulgens). We
      report the occurrence of natural A. vasorum infections in a group of captive
      meerkats (Suricata suricatta), housed at a university facility in Switzerland. A.
      vasorum first-stage larvae (L1) were initially identified in a pooled faecal
      sample. Individual samples, investigated with the Baermann-Wetzel technique,
      revealed that 41% (7/17) of the meerkats were infected, with ranges of 2-125 L1/g
      faeces. PCR and sequencing of part of the ITS-2 region resulted in 100% identity
      with A. vasorum. Infected animals did not show clinical signs. One meerkat died
      two days after diagnosis. Upon necropsy one adult specimen was recovered;
      histological examination of the lung revealed granulomatous pneumonia caused by
      A. vasorum larvae and eggs as well as intima and media hyperplasia and isolated
      arteriosclerosis of larger lung vessels. However, the cause of death was a spleen
      rupture with associated blood loss. All meerkats were topically treated with 10
      mg imidacloprid/2.5 mg moxidectin per animal, after which they became negative in
      all follow up faecal examinations. Potential intermediate (gastropods) and
      paratenic hosts (birds) were collected from within or outside the meerkats
      enclosure. Gastropods were examined by PCR and bird samples by digestion. Four
      out of 193 (2.1%) gastropod samples were positive for A. vasorum, whereas none of
      the bird samples were positive. Meerkats, belonging to the Herpestidae, therefore
      are suitable definitive hosts for A. vasorum, with production and excretion of
      live L1. Meerkats kept in captivity in areas where A. vasorum is endemic and with
      potential contact to intermediate hosts are at risk of infection. Regular faecal
      examinations including Baermann-Wetzel technique should be considered.

PMID- 29379714
TI  - Hemispherotomy for late post-traumatic super-refractory status epilepticus in an
      adult.

PMID- 29379715
TI  - State of the Journal 2018: HeartRhythm Case Reports.

PMID- 29379716
TI  - Ectopic atrial tachycardia originating from right atrial appendage aneurysms in
      children: Three case reports.

PMID- 29379717
TI  - Cryoballoon pulmonary vein isolation and voltage mapping for symptomatic atrial
      fibrillation 9 months after Watchman device implantation.

PMID- 29379718
TI  - Peri-coronary sinus atrial flutter associated with prior slow pathway ablation.

PMID- 29379719
TI  - Genotype-phenotype-guided medical and surgical intervention in long QT syndrome.

PMID- 29379720
TI  - Clinical and electrophysiological features of respiratory cycle-dependent atrial
      tachycardia: An analysis of three cases.

PMID- 29379721
TI  - His bundle capture proximal to the site of bundle branch block: A novel pitfall
      of the para-Hisian pacing maneuver.

PMID- 29379722
TI  - A novel mapping technique to detect non-pulmonary vein triggers: A case report of
      self-reference mapping technique.

PMID- 29379723
TI  - Subcutaneous ICD lead position affects defibrillation threshold.

PMID- 29379724
TI  - Impact of a novel algorithm designed to reduce T-wave oversensing with the
      subcutaneous defibrillator in a patient with type I Brugada electrocardiogram.

PMID- 29379725
TI  - Multipolar electrode spline embolization.

PMID- 29379726
TI  - Disseminated Mycobacterium simiae infection in a non-immunosuppressed patient in
      the USA.

PMID- 29379727
TI  - Updates in prostate cancer detections and treatments - Messages from 2017 EAU and
      AUA.

PMID- 29379728
TI  - Current consensus and controversies on male LUTS/BPH (part two).

PMID- 29379729
TI  - Commentary on "Solving the benign prostatic hyperplasia puzzle".

PMID- 29379730
TI  - Innovative endoscopic enucleations of the prostate - Xie's Prostate Enucleations.
AB  - In the past 2 decades, endoscopic enucleation of the prostate has become a safe
      and effective surgical treatment for benign prostatic hyperplasia (BPH), with
      comparable outcomes to traditional surgeries. Transurethral vapor enucleation and
      resection of the prostate (TVERP), transurethral vapor enucleation of the
      prostate (TVEP), and ultrasound-navigated TVEP (US-TVEP) are new, innovative
      endoscopic enucleation procedures. These procedures are named Xie's Prostate
      Enucleations (Xie's Procedures for short). Current clinical data indicate that
      Xie's Procedures are safe and effective treatment options for patients with BPH,
      especially for patients with larger prostates. Further prospective, randomized
      clinical trials compared with traditional transurethral resection of prostate
      (TURP) are still needed.

PMID- 29379731
TI  - Underactive bladder: Pathophysiology and clinical significance.
AB  - Underactive bladder (UAB) is a voiding disorder which generates disabling lower
      urinary tract symptoms (LUTS) due to the inability to produce an effective
      voiding contraction sufficient to empty the bladder. The underlying abnormality,
      that is usually appreciated when performing urodynamic studies, has been defined
      by the International Continence Society (ICS) as detrusor underactivity (DUA).
      DUA is a common yet under-researched bladder dysfunction. The prevalence of DUA
      in different patient groups suggests that multiple aetiologies are implicated.
      Currently there is no effective therapeutic approach to treat this condition. An
      improved understanding of the underlying mechanisms is needed to facilitate the
      development of new advances in treatment. The purpose of this review is to
      discuss the epidemiology, pathophysiology, common causes and risk factors
      potentially leading to DUA; to aid in the appropriate diagnosis of DUA to
      potentially improve treatment outcomes.

PMID- 29379732
TI  - Update on minimally invasive surgery and benign prostatic hyperplasia.
AB  - Transurethral resection of the prostate (TURP) became the gold standard surgical
      treatment for benign prostatic obstruction without undergoing randomized
      controlled trials against the predecessor standard in open suprapubic
      prostatectomy. TURP has historically been associated with significant morbidity
      and this has fuelled the development of minimally invasive surgical treatment
      options. Improvements in perioperative morbidity for TURP has been creating an
      ever increasing standard that must be met by any new technologies that are to be
      compared to this gold standard. Over recent years, there has been the emergence
      of novel minimally invasive treatments such as the prostatic urethral lift (PUL;
      UroLift System), convective WAter Vapor Energy (WAVE; Rezum System), Aquablation
      (AQUABEAM System), Histotripsy (Vortx Rx System) and temporary implantable
      nitinol device (TIND). Intraprostatic injections (NX-1207, PRX-302, botulinum
      toxin A, ethanol) have mostly been used with limited efficacy, but may be
      suitable for selected patients. This review evaluates these novel minimally
      invasive surgical options with special reference to the literature published in
      the past 5 years.

PMID- 29379733
TI  - The use of 5-alpha reductase inhibitors in the treatment of benign prostatic
      hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is characterized by an enlarged prostate,
      lower urinary tract symptoms (LUTS), and a decreased urinary flow rate. Common in
      older men, BPH is a progressive disease that can eventually lead to complications
      including acute urinary retention (AUR) and the need for BPH-related surgery.
      Both normal and abnormal prostate growth is driven by the androgen
      dihydrotestosterone (DHT), which is formed from testosterone under the influence
      of 5-alpha reductase. Thus, 5-alpha reductase inhibitors (5-ARIs) effectively
      reduce the serum and intraprostatic concentration of DHT, causing an involution
      of prostate tissue. Two 5-ARIs are currently available for the treatment of BPH
      finasteride and dutasteride. Both have been demonstrated to decrease prostate
      volume, improve LUTS and urinary flow rates, which ultimately reduces the risk of
      AUR and BPH-related surgery. Therefore, either alone or in combination with other
      BPH medications, 5-ARIs are a mainstay of BPH management.

PMID- 29379734
TI  - Botulinum toxin and benign prostatic hyperplasia.
AB  - Benign prostatic hyperplasia (BPH) is a clinical condition where lower urinary
      tract symptoms are caused by both a physically obstructing prostate as well as
      tight smooth muscles around the bladder outlet. Treatment of this condition with
      botulinum toxin has been used since 2003, but this interest has somewhat died
      down after two large randomized controlled trials (RCTs) showing equivalence of
      results between their treatment and placebo arms. However, with review of animal
      studies and unexplained exaggerated effect of the placebo arms of the two RCTs,
      together with recent data of sustained benefits after 18 months of treatment, the
      place of botulinum toxin in the BPH field is probably still present.

PMID- 29379735
TI  - Laparoscopic adenomectomy in BPH - Does it have a role today?
AB  - Symptomatic benign prostatic hyperplasia (BPH) is managed medically worldwide,
      but transurethral resection of prostate (TURP) is the gold standard in refractory
      cases. Holmium laser enucleation of prostate (HoLEP), laser vaporization are
      other options which are widely practiced. However in larger glands which are more
      than 80 g, open adenomectomy is still practiced. Laparoscopic adenomectomy is a
      minimally invasive option in such circumstances. This article explains about
      different techniques in minimally invasive adenomectomy and the role for this
      procedure today. Laparoscopic simple prostatectomy (LSP) has a place in
      symptomatic, larger prostatic adenoma in the hands of experienced laparoscopic
      surgeons when open simple prostatectomy is needed.

PMID- 29379736
TI  - Non-invasive evaluation of lower urinary tract symptoms (LUTS) in men.
AB  - Lower urinary tract symptoms (LUTS) are common in males over the age of 40 years
      old and are likely to increase with an aging population. Currently urodynamic
      studies are the gold standard to determine the aetiology of voiding dysfunction
      and LUTS. However, due to its invasive nature, a great number of non-invasive
      ultrasound based investigations have been developed to assess patients with
      symptomatic LUTS. The clinical application of non-invasive tests could
      potentially stratify patients who would require more invasive investigations and
      allow more precise patient directed treatment. A PubMed literature review was
      performed and we will discuss the non-invasive investigations that have been
      developed thus far, focusing on bladder wall and detrusor wall thickness (BWT &
      DWT), ultrasound estimated bladder weight (UEBW) and intravesical prostatic
      protrusion (IPP).

PMID- 29379737
TI  - Bipolar transurethral enucleation and resection of the prostate: Whether it is
      ready to supersede TURP?
AB  - Objective: According to the EAU Guidelines, transurethral resection of the
      prostate (TURP) has so far still been considered as the gold standard for
      surgical treatment for patients with obstructing clinical benign prostate
      hyperplasia (BPH). However, its relatively high rate of complications and
      postoperative recurrence necessitates further modification and innovation on the
      surgery technique. We reported the patient outcomes with our technique. Methods:
      We retrospectively analyzed 52 patients with obstructing clinical BPH who
      underwent bipolar transurethral enucleation and resection of the prostate (B
      TUERP) between March 2015 and September 2015. Pre- and perioperative parameters
      were obtained from medical charts. Postoperative follow-ups were administrated at
      1, 3, 6, 12 and 24 month(s) after surgery, respectively. Results: All the
      operations were performed successfully with a mean operative time of 43.1 min and
      an average tissue removal rate of 74.7%. Qmax was significantly improved
      immediately after surgery, followed by a continuous improvement throughout the
      follow-ups. Following a steep decrease in mean prostate specific antigen (PSA)
      and post void residual (PVR) observed within the first half year after surgery,
      the serum PSA was then maintained at a constant level of 0.61 ng/mL. Temporary
      urinary retention was found in four cases (7.7%). Stress urinary incontinence
      occurred in five patients (9.6%), with the condition resolved in 1-2 weeks
      without extra treatment. Urethral strictures and bladder neck contractures, as
      the most commonly observed long-term complications, developed in four patients
      (7.7%). No recurrence was found during 2 years of follow-ups. An improvement in
      International Index of Erectile Function (IIEF-5) scores was witnessed in 17
      patients preoperatively with normal sexual function during the first 6 months
      after surgery, and sustained throughout the 24-month period. Conclusions:
      Enucleation reflects an improvement on surgical technique in many ways with a
      need for surgical equipment that can be broadly accessible in clinical practice.
      Currently, bipolar resection is a commonly employed procedure in clinical
      settings, and its similarity shared with bipolar enucleation technique warrants a
      quick learning of B-TUERP by urologists. Based on these findings, we believe that
      the substitution of TURP by TUERP as the gold standard for prostate endoscopic
      procedure can be expected in the future.

PMID- 29379738
TI  - Management of advanced adenocarcinoma in Indiana Pouch urinary diversion.
AB  - Adenocarcinoma is a rare finding following urinary diversion with
      gastrointestinal segments. This report describes an 80-year-old woman with a
      history of bladder cancer who subsequently developed a pT4 adenocarcinoma 8 years
      following her radical cystectomy and Indiana Pouch continent urinary diversion.
      An en bloc resection of the pouch and affected small bowel was performed and the
      patient underwent conversion to an ileal conduit diversion. We use this case to
      highlight a mechanism for possible pathogenesis and the management of
      adenocarcinoma in urinary diversions including the need for regular surveillance
      and the surgical approach.

PMID- 29379739
TI  - Extrarenal calyces as a cause of non-functional kidney in a child: Case report.

PMID- 29379740
TI  - Recurrent papillary renal cell carcinoma with concomitant ipsilateral upper
      urinary tract urothelial carcinoma and metachronous urothelial carcinoma of the
      bladder.

PMID- 29379741
TI  - Post traumatic isolated bladder neck transection: Unreported and undescribed
      injury.

PMID- 29379742
TI  - Selective arterial embolization for uncontrollable urethral hemorrhage in a
      patient with a left ventricular assist device.

PMID- 29379743
TI  - Evaluation of acute toxicity of triazophos and deltamethrin and their inhibitory
      effect on AChE activity in Channa punctatus.
AB  - Pesticides are applied to control the pests indoor and outdoor; however, their
      remarkable amount reaches to the aquatic system through various routes like run
      off, leaching, spray-drift, effluent from factories. These are reported to have
      negative metabolic impact on different non-target aquatic organisms like fishes.
      Thus, present study is aimed to evaluate the acute toxicity of two groups of
      pesticides, organophosphate and pyrethroid, namely triazophos and deltamethrin,
      respectively. The test was conducted for 96 h period in a freshwater teleost,
      Channa punctatus. The LC50 values for triazophos and deltamethrin after 96 h
      treatment was found to be 0.069 mg/L and 7.33 MUg/L. The deltamethrin was found
      to be about ten times more toxic than triazophos to the fish. In treated fish,
      alterations in various behavioural patterns were observed with increasing
      concentrations of both the pesticides as compared to control. Further, tissue
      specific as well as dose dependent inhibition in the acetylcholinesterase (AChE,
      EC 3.1.1.7) activity was found in brain, muscle and gills in Channa punctatus
      exposed to both the insecticides. However, the effect was more pronounced in
      triazophos treated fishes than the deltamethrin. A futuristic approach on
      biochemical and molecular studies may throw light on the mechanism of action of
      these pesticides.

PMID- 29379744
TI  - The relationship between IQ and performance on the MATRICS consensus cognitive
      battery.
AB  - The associations between IQ and individual tests of neurocognitive function are
      well studied. However, there is a lack of information as to how IQ relates to
      performance on neuropsychological test batteries as a whole and in the same
      individuals. In this study, 250 healthy participants aged 20-69 years were tested
      with the Wechsler Abbreviated Scale of Intelligence (WASI) and the MATRICS
      Consensus Cognitive Battery (MCCB). In correlation analyses, IQ was significantly
      related to all MCCB scores, except the Social Cognition domain. Hierarchical
      regression analyses including gender, age, and education confirmed this
      association. For overall cognitive function, 50% of the variance was explained by
      IQ and demographic characteristics. For the domains Speed of Processing, Working
      Memory, Visual and Verbal Learning, IQ explained a larger proportion of the
      variance than the demographic factors did. The implication is that these domains
      may provide information of a person's intelligence level.

PMID- 29379745
TI  - Facial emotion recognition impairment is related to disorganisation in multi
      episode schizophrenia.
AB  - The present investigation explores the relationship between facial emotion
      recognition (FER) and symptom domains in three groups of schizophrenia spectrum
      patients (43 ultra-high-risk, 50 first episode and 44 multi-episode patients) in
      which the existence of FER impairment has already been demonstrated. Regression
      analysis showed that symptoms and FER impairment are related in multi-episode
      patients, regardless of the illness duration. We suggest that the link between
      symptoms and FER impairment is involved in the progression of the disease.

PMID- 29379746
TI  - Utility of the UCSD Performance-based Skills Assessment-Brief Japanese version:
      discriminative ability and relation to neurocognition.
AB  - The UCSD Performance-based Skills Assessment Brief (the UPSA-B) has been widely
      used for evaluating functional capacity in patients with schizophrenia. The
      utility of the battery in a wide range of cultural contexts has been of concern
      among developers. The current study investigated the validity of the Japanese
      version of the UPSA-B as a measure of functional capacity and as a co-primary for
      neurocognion. Sixty-four Japanese patients with schizophrenia and 83 healthy
      adults entered the study. The Japanese version of the UPSA-B (UPSA-B Japanese
      version) and the MATRICS Cognitive Consensus Battery Japanese version (MCCB
      Japanese version) were administered. Normal controls performed significantly
      better than patients, with large effect sizes for the Total and the subscale
      scores of the UPSA-B. Receiver Operating Characteristic (ROC) curve analysis
      revealed that the optimal cut-off point for the UPSA-B Total score was estimated
      at around 80. The UPSA-B Total score was significantly correlated with the MCCB
      Composite score and several domain scores, indicating the relationship between
      this co-primary measure and overall cognitive functioning in Japanese patients
      with schizophrenia. The results obtained here suggest that the UPSA-B Japanese
      version is an effective tool for evaluating disturbances of daily-living skills
      linked to cognitive functioning in schizophrenia, providing an identifiable cut
      off point and relationships to neurocognition. Further research is warranted to
      evaluate the psychometrical properties and response to treatment of the Japanese
      version of the UPSA-B.

PMID- 29379747
TI  - Supported employment among veterans with serious mental illness: the role of
      cognition and social cognition on work outcome.
AB  - Unemployment is a primary functional deficit for the majority of adults with
      schizophrenia. Research indicates that over two-thirds of adults living in the
      community with schizophrenia are unemployed. Despite effective programs to assist
      with job identification and placement, the ability to attain and maintain
      employment remains a pressing concern. Neurocognitive functioning is widely
      acknowledged to be a determinant of work outcome; however, effect sizes tend to
      be in the small to medium range. The present study sought to further understand
      the determinants of work outcome among a sample of 104 veterans with
      schizophrenia enrolled in a supported employment program. A small percentage of
      veterans in the study got competitive jobs; 53% who secured jobs maintained
      employment for longer than 6 months. Cognition, social cognition, and symptoms
      were unrelated to job attainment. However, speed of processing and social
      cognition were significant predictors of work outcomes such as wages and tenure.
      These findings suggest that cognitive abilities including processing speed and
      the ability to accurately interpret and respond to social cues are significant
      determinants of whether individuals with schizophrenia remain employed. The
      results are discussed in light of current available treatment options and domains
      to target in synergy with work rehabilitation efforts.

PMID- 29379748
TI  - Cognitive functioning among patients with schizophrenia in a Nigerian hospital: a
      comparison with mood disorder.
AB  - Objective: The study aimed to investigate correlates of cognition among patients
      with schizophrenia. Methods: Over a three month period, in-patients diagnosed
      with schizophrenia (n = 50) and mood disorders (n = 50) were recruited into the
      study. Both groups of patients were assessed using the Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN), the Annett Hand Preference Questionnaire
      (AHPQ) and the Global Assessment of Function Scale (GAF). Patients with
      schizophrenia were further assessed using the Positive and Negative Syndromes
      Scale, PANSS and the Clinical Global impression (CGI). The cognitive screen
      section of SCAN (comprising Verbal Trails Test and Mini Mental State examination,
      MMSE) and the cognitive factor of PANSS were used to assess cognitive function.
      Results: No differences were found in the cognitive profile of patients with
      schizophrenia and mood disorder. Among patients with schizophrenia, poor verbal
      performance was associated with the negative or mixed syndrome (p = 0.004), left
      or mixed handedness (p = 0.013), greater illness severity (p = 0.030) and lower
      GAF scores (p = 0.039). Poor performance on MMSE correlated with higher total
      PANSS score (p = 0.022) and was also associated with the negative or mixed
      syndrome (p = 0.003) and lack of clinical improvement (p = 0.035). Conclusion:
      Patients with the negative or mixed schizophrenia syndrome may suffer more
      cognitive deficit. Poor verbal performance among patients with schizophrenia may
      be associated with left or mixed handedness, more severe illness and poor
      functioning.

PMID- 29379749
TI  - Overconfidence in incorrect perceptual judgments in patients with schizophrenia.
AB  - Background: Patients with schizophrenia show overconfidence in memory and social
      cognition errors. The present investigation examined whether this cognitive
      distortion also manifests in perceptual tasks. Methods: A total of 55 individuals
      with schizophrenia, 58 with obsessive-compulsive disorder (OCD) as well as 45 non
      clinical controls were presented 24 blurry black and white pictures, half of
      which contained a hidden object; the other half contained ("snowy") visual noise.
      Participants had to judge whether the pictures depicted an object or not and how
      confident they were in this judgment. Results: Participants with schizophrenia
      showed overconfidence in errors and an enhanced knowledge corruption index (i.e.
      rate of high-confident errors on all high-confident responses) relative to both
      control groups. In contrast, accuracy scores did not differ between clinical
      groups. Metacognitive parameters were correlated with self-rated levels of
      current paranoia. Discussion: To the best of our knowledge, this is the first
      study to demonstrate overconfidence in errors among individuals with psychosis
      using a visual perception task. Speaking to the specificity of this abnormality
      for schizophrenia and its pathogenetic relevance, overconfidence in errors and
      knowledge corruption were elevated in patients with schizophrenia relative to
      both control groups and were correlated with paranoia.

PMID- 29379750
TI  - Social cognition and social judgment in schizophrenia.
AB  - Schizophrenia typically involves poor social functioning. This may be due, in
      part, to deficits in theory-of-mind, the cognitive ability to reason flexibly
      about the mental states of others. Patients also have deficits in social
      knowledge. It is currently unclear how these two impairments interrelate in
      schizophrenia. To address this issue, 43 patients with schizophrenia and 25
      healthy controls completed two theory-of-mind tests and a novel test of social
      judgment. This latter measure required participants to judge whether various
      social behaviors were normal or reasonable in the context in which the behaviors
      occurred. Whereas patients demonstrated clear deficits in theory-of-mind, they
      performed similarly to controls when judging socially appropriate behaviors and
      violations of social norms. Patients, however, were less likely than controls to
      judge social behavior as reasonable when the behavior was impolite but
      understandable if the characters' thoughts were taken into account. This latter
      difficulty correlated with patients' performance deficits on the theory-of-mind
      tasks. Overall, findings suggest that basic social knowledge is intact in
      schizophrenia, though judgments of social behavior are affected by patients'
      theory-of-mind deficits.

PMID- 29379751
TI  - The effect of cognitive training on evoked potentials in schizophrenia.
AB  - Electrophysiological indices are sensitive to cognitive dysfunction in
      schizophrenia but have rarely been used to assess benefits of cognitive
      remediation. Our aim was to evaluate the effect of specific cognitive training
      approaches on event-related potentials. Forty-six patients with schizophrenia
      underwent either auditory (AUD) or visuo-spatial (VIS) cognitive training or
      treatment-as-usual (TAU). Cognitive training was computer-assisted and
      administered for 10 sessions within two weeks. Event-related potentials during an
      active odd-ball paradigm together with clinical and neuropsychological variables
      were assessed before and after training and again at a two-month follow-up.
      Compared to the TAU group both the AUD and VIS training groups showed decreased
      P2 latency following training. At follow-up, the P2-latency reduction was stable
      in the VIS group but the AUD group experienced a relapse. Training resulted in
      improved digit-span backward among neuropsychological variables. Increased P2
      amplitude was related to more positive symptoms and lower social-occupational
      functioning and longer P2 latency was associated with greater severity of
      stereotyped thinking. The more general visuo-spatial training appears to have a
      longer-lasting effect on P2 latency than the specific auditory training.
      Alternatively, there may be specific auditory discrimination deficits in
      schizophrenia requiring more extensive training for a stable change.

PMID- 29379752
TI  - Consensus five factor PANSS for evaluation of clinical remission: effects on
      functioning and cognitive performances.
AB  - : Criteria developed by the Remission in Schizophrenia Working Group (RSWG),
      based upon 8 core symptoms of PANSS, are generally used for evaluation of
      Remission. However, some concerns have arisen as regard to the ability of the
      RSWG criteria to detect truly remitted cases. This study aims to compare the
      severity criteria of remission defined by the RSWG (RSWG-cr) with more
      restrictive criteria, based upon the use of PANSS factor model. Methods: 112
      chronic psychotic outpatients were examined. Symptomatic remission according to
      RSWGcr was compared with remission according to criteria based on the 20-items of
      PANSS considered in the consensus five factor model (PANSS-FCTcr), in relation to
      functional and neurocognitive outcomes. Results: Data from the study demonstrated
      the superiority of PANSS-FCTcr in identifying patients with higher functional and
      cognitive outcomes. Conclusion: PANSS-FCTcr seems to be suitable for use in both
      common clinical practice and research setting, being associated with improved
      identification of truly remitted patients.

PMID- 29379753
TI  - Editorial.

PMID- 29379754
TI  - Social cognition in patients with schizophrenia spectrum and bipolar disorders
      with and without psychotic features.
AB  - Background: Social cognition may be critical to the impoverished social
      functioning seen in serious mental illness. However, although social-cognitive
      deficits are consistently demonstrated in schizophrenia spectrum disorders (SSD),
      studies in bipolar disorder (BD) have produced inconsistent results. This
      inconsistency may relate to symptom profiles of patients studied, particularly
      the presence or absence of psychotic features. Thus, we examined social cognition
      in bipolar disorder with psychotic features (BD +) versus without psychotic
      features (BD -) relative to SSD and controls. Methods: A sample of 537 SSD
      patients, 85 BD + patients, 37 BD - patients, and 309 controls were administered
      the MATRICS Consensus Cognitive Battery, including a social cognition measure,
      the managing emotions branch of the Mayer-Salovey-Caruso Emotional Intelligence
      Test (MSCEIT). Analyses of covariance compared MSCEIT performance between
      diagnostic groups while controlling for race, psychotropic medication status, and
      neurocognition. Results: SSD but not BD - or BD + patients showed significant
      MSCEIT deficits relative to controls. Conclusions: MSCEIT deficits were found in
      SSD but not BD - or BD +, suggesting that social cognition may represent an
      underlying difference between SSD and BD. However, variance in MSCEIT performance
      among BD patients may also suggest latent BD subgroups characterized by social
      cognitive deficits. Findings can help inform future investigations into how
      social cognition and social brain development differ between SSD and BD.

PMID- 29379755
TI  - Neurocognitive deficits are relevant for the jumping-to-conclusions bias, but not
      for delusions: A longitudinal study.
AB  - Patients with delusions exhibit an increased tendency to arrive at decisions
      based on very limited evidence (jumping-to-conclusions; JTC), making this
      reasoning bias relevant for the treatment of delusions. Neurocognitive deficits
      contribute to JTC, but it is not known whether this has any bearing on the
      clinical syndrome of delusions. We addressed this question by reanalyzing data
      from an efficacy study of non-pharmacological interventions as adjunctive
      treatments in schizophrenia. We investigated the longitudinal associations of
      cognitive functioning, JTC and delusions in patients with psychotic disorders
      receiving either a metacognitive intervention addressing reasoning biases (n =
      59), or cognitive remediation (n = 58). Both interventions improved JTC; in the
      cognitive remediation group, tentative evidence suggested that better
      neurocognitive performance contributed to this improvement. However, JTC gains
      were associated with delusion improvement only in the metacognitive intervention
      group, suggesting a content-specific mechanism of action.

PMID- 29379756
TI  - Specificity of facial emotion recognition impairments in patients with multi
      episode schizophrenia.
AB  - Background: Patients with schizophrenia show impairments in social information
      processing, such as recognising facial emotions and face identity. Goal: The aim
      of this study was to explore whether these impairments represent specific
      deficits or are part of a more general cognitive dysfunction. Method: Forty-two
      patients with schizophrenia and 42 matched controls were compared on facial
      emotion and face identity recognition versus (non-social) abstract pattern
      recognition, using three tasks of the Amsterdam Neuropsychological Tasks (ANT)
      program. Results: Patients were slower than controls in social information
      processing as well as in (non-social) abstract pattern recognition. Patients were
      also less accurate than controls in processing social information, but not in
      recognition of abstract patterns. Differences between patients and controls were
      most substantial for facial emotion recognition compared to both face identity
      recognition (speed) and non-social pattern recognition (speed and accuracy).
      Finally, differences between patients and controls were largest for the
      recognition of negative emotions. Conclusion: Compared to controls patients with
      schizophrenia displayed more difficulties in processing of social information
      compared to non-social information. These results support the hypothesis that
      facial emotion recognition impairment is a relatively distinct entity within the
      domain of cognitive dysfunction in schizophrenia.

PMID- 29379757
TI  - UCSD Performance-Based Skills Assessment (UPSA): validation of a Brazilian
      version in patients with schizophrenia.
AB  - The UCSD Performance-based Skills Assessment (UPSA) is a measure of Functional
      Capacity and assesses skills involved in community tasks. It has good
      psychometrics properties, and is currently recommended as a co-primary assessment
      of cognition in the MATRICS Project. To our knowledge so far, there are no
      studies in western developing countries concerning Functional Capacity in
      Schizophrenia. The aims of this study were to translate, culturally adapt and
      validate the UPSA to assess Functional Capacity in community-dwelling patients
      with Schizophrenia living in Brazil. Eighty-two subjects (52 patients, 30
      controls) were evaluated using: the Brazilian version of the UPSA (UPSA-1-BR),
      PANSS, Personal and Social Performance (PSP) and Global Assessment of Functioning
      (GAF). In the reliability test, UPSA-1-BR showed good Internal Consistency
      (Cronbach's alpha of 0.88) and strong correlation between test and retest (4
      month gap; r = 0.91; p < 0.01). Spearman's rho values showed a moderate
      correlation between UPSA-1-BR and both PSP (0.50; p < 0.01) and GAF (0.46; p <
      0.01) scores. UPSA-1-BR is capable of differentiating people with and without
      Schizophrenia. Patients scored lower than controls (58.9 versus 79.1), with an
      AUC of 0.79 (95%IC: 0.69-0.89). Sensitivity and specificity values of 0.71 and
      0.70, respectively, were found in the cut-off point of 73.5, for separation of
      patients and controls, with predictive values of 80% (positive) and 58%
      (negative). UPSA-B-BR was also evaluated. UPSA-1-BR and its brief version
      presented adequate psychometric properties and proved to be valid and reliable
      instruments in the assessment of Functional Capacity in subjects with
      Schizophrenia.

PMID- 29379758
TI  - Smoking in schizophrenia: cognitive impact of nicotine and relationship to
      smoking motivators.
AB  - Smoking prevalence in schizophrenia is significantly elevated relative to other
      clinical and to non-clinical groups. The cognitive self-medication hypothesis
      attributes this to the beneficial effects of nicotine on illness-related
      cognitive deficits. Significant effects of nicotine have been observed on visual
      spatial working memory (VSWM), sustained attention (Continuous Performance Test -
      Identical Pairs; CPT-IP) and prepulse inhibition (PPI). It remains unclear
      whether these neurophysiological and neurocognitive effects of nicotine influence
      self-reported smoking motivation. To explore the relationship between nicotine
      effects on cognition and self-reported smoking motivation in schizophrenia and
      non-psychiatric control smokers, the impact of smoking abstinence and
      reinstatement was examined across three cognitive indices (VSWM, CPT-IP, PPI) and
      compared to self-reported smoking motivation (Modified Reasons for Smoking Scale
      revised to include 'cognitive motivators'). Cognitive function was assessed after
      'typical' smoking and overnight abstinence. Schizophrenia smokers (but not
      controls) demonstrated significantly less error on the VSWM task in the smoking
      relative to abstinent condition. Control (but not schizophrenia) smokers, showed
      evidence of CPT-IP improvement in the smoking relative to abstinent condition.
      The overall profile of smoking motivation was comparable between groups. However,
      significant relationships between subjective and objective indices of smoking
      related cognitive change were observed for controls. Differential effects of
      nicotine on cognition have been hypothesised to influence the pattern and
      persistence of smoking in schizophrenia. These preliminary findings indicate that
      evidence for such effects is apparent even in small samples - particularly for
      VSWM. This is the first study to show that neurocognitive effects of smoking may
      influence self-reported smoking motivation.

PMID- 29379759
TI  - Insight and illness perception in Mexican patients with psychosis.
AB  - Background: Insight and illness perception are two concepts of interest in the
      study of factors related to clinical outcome in patients with psychosis. Insight
      implies a risk of emotional distress for the patient. Illness perceptions,
      regardless of their accuracy, might be favorable or not to illness. Literature
      provides evidence of significant correlates of these factors with clinical
      outcome, but they are rarely included in a single study. Objectives: 1) assessing
      insight and illness perception in a sample of Mexican patients who have
      experienced psychosis and, 2) analyzing how insight and illness perception relate
      to each other and how they relate to clinical status (i.e., positive, negative,
      and general psychopathology, depression, and anxiety). Methods: Sixty-one
      participants (55.7% females) were recruited from a public psychiatric hospital;
      insight and illness perceptions were assessed with the SUMD and the Brief-IPQ,
      respectively. Clinical status was assessed with the PANSS, CDS and BAI scales.
      Results: Participants showed good insight, favorable illness perceptions for the
      cognitive and comprehension dimensions, but unfavorable for the emotional
      dimension. Clinical status of sample was characterized by mild symptoms. Poor
      insight related to positive symptoms and general psychopathology. Cognitive and
      emotional perceptions of illness were significantly associated to most clinical
      status parameters, whereas comprehension showed no significant results.
      Conclusions: The study not only replicates the significant association on insight
      and illness perception with clinical outcome, but shows how their patterns of
      interactions are different, reinforcing the idea that they are two distinct
      factors worthy of being habitually acknowledged in research and clinical
      practice.

PMID- 29379760
TI  - Factors predicting work outcome in Japanese patients with schizophrenia: role of
      multiple functioning levels.
AB  - Functional outcomes in individuals with schizophrenia suggest recovery of
      cognitive, everyday, and social functioning. Specifically improvement of work
      status is considered to be most important for their independent living and self
      efficacy. The main purposes of the present study were 1) to identify which
      outcome factors predict occupational functioning, quantified as work hours, and
      2) to provide cut-offs on the scales for those factors to attain better work
      status. Forty-five Japanese patients with schizophrenia and 111 healthy controls
      entered the study. Cognition, capacity for everyday activities, and social
      functioning were assessed by the Japanese versions of the MATRICS Cognitive
      Consensus Battery (MCCB), the UCSD Performance-based Skills Assessment-Brief
      (UPSA-B), and the Social Functioning Scale Individuals' version modified for the
      MATRICS-PASS (Modified SFS for PASS), respectively. Potential factors for work
      outcome were estimated by multiple linear regression analyses (predicting work
      hours directly) and a multiple logistic regression analyses (predicting
      dichotomized work status based on work hours). ROC curve analyses were performed
      to determine cut-off points for differentiating between the better- and poor work
      status. The results showed that a cognitive component, comprising visual/verbal
      learning and emotional management, and a social functioning component, comprising
      independent living and vocational functioning, were potential factors for
      predicting work hours/status. Cut-off points obtained in ROC analyses indicated
      that 60-70% achievements on the measures of those factors were expected to
      maintain the better work status. Our findings suggest that improvement on
      specific aspects of cognitive and social functioning are important for work
      outcome in patients with schizophrenia.

PMID- 29379761
TI  - Neurocognition as a predictor of outcome in schizophrenia in the Northern Finland
      Birth Cohort 1966.
AB  - The purpose of this study was to study neurocognitive performance as a predictor
      of outcomes in midlife schizophrenia. There is a lack of studies with unselected
      samples and a long follow-up. The study is based on the prospective, unselected
      population-based Northern Finland Birth Cohort 1966. The study includes 43
      individuals with schizophrenia and 73 controls, whose neurocognitive performance
      was assessed twice, at 34 and 43 years. At both time points we used identical
      neurocognitive tests to assess verbal and visual memory and executive functions.
      Our main aim was to analyse neurocognitive performance at 34 years as a predictor
      of clinical, vocational and global outcomes at 43 years. Additionally, the
      analysis addressed cross-sectional associations between cognitive performance and
      clinical, vocational and global measures at 43 years. The assessment of outcomes
      was performed in the schizophrenia group only. In the longitudinal analysis
      poorer visual memory predicted poorer vocational outcome and poorer long-term
      verbal memory predicted poorer global outcome. In the cross-sectional analysis
      poorer visual memory and lower composite score of neurocognition were associated
      with poorer global outcome. No individual neurocognitive test or the composite
      score of these predicted remission. These data indicate that neurocognition,
      especially memory function, is an important determinant of long-term functional
      outcome in midlife schizophrenia.

PMID- 29379762
TI  - Poor premorbid school performance, but not severity of illness, predicts
      cognitive decline in schizophrenia in midlife.
AB  - Neurocognitive dysfunction is common in schizophrenia but its course and
      determinants remain uncertain. Our aim was to analyse if premorbid school
      performance and the severity of illness and functioning predict change in
      cognition in schizophrenia in a general population sample. The sample included
      cases with schizophrenia spectrum disorder from the Northern Finland Birth Cohort
      1966. Data on school marks at the age of 16 years, educational level at the age
      of 34 years, severity of symptoms and occupational functioning around first
      episode and after years of illness were gained from national registers, hospital
      notes and interviews. Change of verbal and visual learning and memory and
      executive functioning were examined between ages 34 and 43 years. The number of
      cases varied in analyses from 29 to 41, depending on missing data in particular
      cognitive tests. Lower school marks at age 16 years and lower education at age 34
      years predicted more decline of cognition. Measures of severity of illness or
      functioning were not associated statistically significantly with change of
      cognition. Premorbid school performance, but not later course of schizophrenia,
      related to change of cognition in midlife. Poor premorbid scholastic performance
      and post-onset cognitive decline may represent related processes as part of an
      endophenotype of schizophrenia.

PMID- 29379763
TI  - Cognitive deficits characterization using the CogState Research Battery in first
      episode psychosis patients.
AB  - The computer-based CogState Research Battery (CSRB) proposes a test structure
      which follows MATRICS recommended cognitive domains but lacks direct comparison
      to pen and paper batteries in first-episode psychosis (FEP). The aim of this
      study was to compare performances obtained with the CSRB and a pen and paper
      battery in a historical cohort of FEP patients. Among patients entering an early
      intervention program between 2003 and 2014, separate cohorts completed the
      traditional pen and paper cognitive battery (n = 182) and the CSRB (n = 97).
      Composite z-scores were derived using normative data of matched controls (n = 64
      pen and paper, n = 69 CSRB) and were compared between the two batteries for the 7
      cognitive domains. The cohort tested using the CSRB performed better on the
      domains of processing speed, attention, visual memory, and verbal memory than the
      cohort tested using the pen and paper battery (all p < 0.001). Performance did
      not differ between the two types of batteries for the working memory, executive
      functions, and social cognition domains. Cognitive profiles identified in the two
      patient cohorts were similar, with verbal memory being the most impaired domain.
      Better performances on the CSRB may be primarily due to the minimal demand of the
      computerized tests on graphomotor abilities and reading speed compared to the pen
      and paper tests. Our investigation offers a better understanding on how the
      results obtained with computerized batteries may compare to earlier work done
      with traditional tests.

PMID- 29379764
TI  - Cognitive Performance associated to functional outcomes in stable outpatients
      with schizophrenia.
AB  - Background-objective: Prevalence data of cognitive impairment in Schizophrenia
      based on large population samples are scarce. Our goal is to relate cognition and
      functional outcomes, and estimate prevalence of cognitive impairment in a large
      sample of schizophrenia outpatients treated with second-generation
      antipsychotics. Method: A cross-sectional outpatient evaluation conducted during
      follow-up visits. Selection criteria included six-months stable treatment. The
      brief battery, EPICOG-SCH, covered four cognitive domains related to functional
      outcomes: working memory (WAIS-III-Letter-Number-Sequencing), executive function
      (Category Fluency Test; CFT), verbal memory (WMS-III-Logical-Memory), and
      information processing speed (Digit-Symbol-Coding and CFT). Clinical severity and
      functional impairment were assessed with CGI-SCH and WHO DAS-S. Impairment
      prevalence was calculated at <= 1.5 SD. Results: Among patients recruited (n =
      848) in 234 participating centers, 672 were under 6-month treatment. 61.5% (n =
      413) reported cognitive impairment according to CGI-SCH Cognitive Subscale.
      Estimated prevalences were 85.9% (95% CI 85.6-86.2%) CFT-Fruits; 68.3% (95% CI
      67.8-68.8%) CFT-Animals; 38.1% (95% CI 37.5-38.3%) Digit-Symbol-Coding; 24.8%
      (95% CI 24.1-25.5%) Verbal Memory-Units; 20.9% (95% CI 20.2-21.6%) Letter-Number
      Sequencing; 11.7% (95% CI 11.0-12.4%) Verbal Memory-Items. Negative and
      Depressive symptoms, Deficit Syndrome, and functional disability were related to
      poor performance. Functional disability was predicted by CGI-SCH-Overall severity
      (OR = 1.34635, p < 0.0001), CGI-SCH-Negative Symptoms (OR = 0.75540, p < 0.0001),
      working memory (Letter-Number-Sequencing) (OR = - 0.16442, p = 0.0004) and the
      time-course (OR = 0.05083, p = 0.0094), explaining 47% of the observed
      variability. Conclusion: Most prevalent impairments were on executive function
      and processing speed domains; however, working memory showed the strongest
      relationship to functional disability. Monitoring cognitive function during
      follow up is critical to understand patient's everyday functional capacity.

PMID- 29379765
TI  - Schizophrenia patients and 22q11.2 deletion syndrome adolescents at risk express
      the same deviant patterns of resting state EEG microstates: A candidate
      endophenotype of schizophrenia.
AB  - Schizophrenia is a complex psychiatric disorder and many of the factors
      contributing to its pathogenesis are poorly understood. In addition, identifying
      reliable neurophysiological markers would improve diagnosis and early
      identification of this disease. The 22q11.2 deletion syndrome (22q11DS) is one
      major risk factor for schizophrenia. Here, we show further evidence that deviant
      temporal dynamics of EEG microstates are a potential neurophysiological marker by
      showing that the resting state patterns of 22q11DS are similar to those found in
      schizophrenia patients. The EEG microstates are recurrent topographic
      distributions of the ongoing scalp potential fields with temporal stability of
      around 80 ms that are mapping the fast reconfiguration of resting state networks.
      Five minutes of high-density EEG recordings was analysed from 27 adult chronic
      schizophrenia patients, 27 adult controls, 30 adolescents with 22q11DS, and 28
      adolescent controls. In both patient groups we found increased class C, but
      decreased class D presence and high transition probabilities towards the class C
      microstates. Moreover, these aberrant temporal dynamics in the two patient groups
      were also expressed by perturbations of the long-range dependency of the EEG
      microstates. These findings point to a deficient function of the salience and
      attention resting state networks in schizophrenia and 22q11DS as class C and
      class D microstates were previously associated with these networks, respectively.
      These findings elucidate similarities between individuals at risk and
      schizophrenia patients and support the notion that abnormal temporal patterns of
      EEG microstates might constitute a marker for developing schizophrenia.

PMID- 29379766
TI  - Different P50 sensory gating measures reflect different cognitive dysfunctions in
      schizophrenia.
AB  - The P50 is an early component of auditory evoked potentials and a measure of
      sensory gating deficits. This evoked potential component is thought to be an
      important endophenotype candidate for schizophrenia. Recent research suggests
      that instead of the P50 ratio, S1 and S2 amplitudes should be evaluated for
      sensory gating. However, no studies have focused on the relationship between
      cognitive dysfunction and P50 sensory gating deficits using S1 and S2 amplitudes.
      The purpose of the present study was to investigate the association between the
      P50 ratio (S2/S1), S1 and S2 amplitudes, and neuropsychological cognitive domains
      using stepwise multiple linear regression analyses. Results demonstrated a
      significant relationship between executive functioning and the P50 ratio and
      between sustained attention and S2 amplitude, respectively. Our findings suggest
      that the P50 ratio and S2 amplitude reflect distinct neurophysiological
      substrates associated with different cognitive functions.

PMID- 29379767
TI  - Time-course and degradation rate of membrane scaffold protein (MSP1D1) during
      recombinant production.
AB  - Membrane scaffold proteins (MSPs) are synthetic derivatives of apolipoprotein A
      I, a major protein component of human high-density lipoprotein complexes. The
      most common among these is the variant MSP1D1, which has been in the focus of
      research on membrane mimetics in the past. As such, the amphipathic MSP1D1 has
      the ability to self-assemble in the presence of synthetic phospholipids into
      discoidal nanoparticles, so called nanodiscs. The recombinant production of MSP
      is exclusively reported using a standard laboratory expression system of the pET
      family. However, strong variations in both yield and achieved concentration as
      well as complications related to unspecific degradation are commonly reported. In
      addition, the time-course of recombinant protein as well as specific protein
      yields have not yet been quantified conclusively. In this study, the time-course
      of MSP1D1 concentration was investigated in a standard pET expression system in
      terms of quantification of production and degradation rates in comparison to a
      reference protein (eGFP).

PMID- 29379768
TI  - Purification and biochemical characterization of an Aspergillus niger phytase
      produced by solid-state fermentation using triticale residues as substrate.
AB  - In this study, an extracellular phytase produced by Aspergillus niger 7A-1, was
      biochemically characterized for possible industrial application. The enzyme was
      purified from a crude extract obtained by solid-state fermentation (SSF) of
      triticale waste. The extract was obtained by microfiltration, ultrafiltration
      (300, 100 and 30 kDa) and DEAE-Sepharose column chromatography. The molecular
      weight of the purified enzyme was estimated to be 89 kDa by SDS-PAGE. The
      purified enzyme was most active at pH 5.3 and 56  degrees C, and retained 50%
      activity over a wide pH range of 4 to 7. The enzymatic thermostability assay
      showed that the enzyme retained more than 70% activity at 80  degrees C for 60 s,
      40% activity for 120 s and 9% after 300 s. The phytase showed broad substrate
      specificity, a Km value of 220 MUM and Vmax of 25 MUM/min. The purified phytase
      retained 50% of its activity with phosphorylated compounds such as phenyl
      phosphate, 1-Naphthyl phosphate, 2-Naphthyl phosphate, p-Nitrophenyl phosphate
      and Glycerol-2-phosphate. The inhibition of phytase activity by metal ions was
      observed to be drastically inhibited (50%) by Ca++ and was slightly inhibited
      (10%) by Ni++, K+, and Na+, at 10 and 20 mM concentrations. A positive effect was
      obtained with Mg++, Mn++, Cu++, Cd++ and Ba++ at 25 and 35% with stimulatory
      effect on the phytase activity.

PMID- 29379769
TI  - Salix alba attenuated oxidative stress in the heart and kidney of
      hypercholesterolemic rabbits.
AB  - Objective: Oxidative stress plays a critical role in the development of
      hypercholesterolemia-induced complications. This study evaluated the effects of
      aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart
      and kidney of hypercholesterolemic rabbits. Materials and Methods: The
      antioxidant activity, as well as total phenolic and salicin content of S. alba
      (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu
      and HPLC methods, respectively. Animals were divided into two groups of control
      (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks).
      Then, hypercholesterolemic animals allocated to the following treatment groups:
      CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD
      plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks.
      MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT
      were evaluated in cardiac and kidney tissues. Results: The scavenging activity,
      total phenolic content and salicin were 19.1 ug/ml (IC50), 153.75 +/- 3.6 mg of
      gallic acid/g, and 18.03 ug/mg, respectively. In comparison to CHO group, MDA
      levels were diminished in Sa and ASA groups but GSH levels were improved. NO
      metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all
      Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups
      and in the kidney of Sa and ASA groups. CAT activity increased in the heart and
      kidney tissues of all Sa and ASA treated groups. Conclusion: The results showed
      S. alba extract improved redox homeostasis in heart and kidney tissues of
      hypercholesterolemic rabbits. The extract antioxidant property may be related to
      its phenolic content.

PMID- 29379770
TI  - Weight Loss and Percutaneous Endoscopic Gastrostomy Tube Placement during
      Chemoradiotherapy for Locally Advanced Cancer of the Oropharynx Do Not Negatively
      Impact Outcomes.
AB  - Objectives: Concurrent chemoradiotherapy is standard of care in locally advanced
      oropharyngeal cancer (LA-OPC). This treatment regimen results in significant
      acute toxicities. This study investigates the effect of treatment-related
      toxicity on patient outcomes. Methods: Patient information was retrospectively
      collected for patients treated for LA-OPC between 2007 and 2014. Factors analyzed
      included age, gender, pretreatment ECOG performance status, smoking history,
      patient BMI prior to and following treatment, tumor histology, disease stage,
      disease recurrence, incidence, and timing of feeding tube placement, radiation
      dose received, chemotherapy regimen used and if it was completed, and patient
      survival. All statistical analysis was provided through the University of
      Nebraska Medical Center Department of Biostatistics. Results: 74 patients were
      identified with a median follow-up of 3.4 years and a median age of 58.5. Most
      patients were male (87.8%) and had squamous cell histology (98.7%). Most patients
      underwent chemoradiotherapy alone (98.6%) and received concurrent cisplatin
      (78.4%) with approximately half (53.4%) receiving all planned chemotherapy. Upon
      multivariate analysis, both disease-free (DFS) and overall survival (OS) rates
      were improved by lower pretreatment BMI, increased weight lost during treatment,
      and lack of percutaneous endoscopic gastrostomy (PEG) tube placement prior to
      treatment initiation. Neither DFS nor OS was impacted by placement of a PEG tube
      during active treatment. Conclusion: These data suggest that weight loss and PEG
      tube placement during chemoradiotherapy for LA-OPC, presumably due to treatment
      associated mucositis and xerostomia, are not associated with worse outcomes.

PMID- 29379772
TI  - The Potential for Topical Probiotic Treatment of Chronic Rhinosinusitis, a
      Personal Perspective.
AB  - This review describes the rationale for topical probiotic intervention, the
      obstacles we are facing and a strategy for future research in the use of
      probiotics to modify CRS symptoms and disease expression. Recent advances in
      molecular microbiology has revealed a plethora of microbial DNA in the nasal
      cavity and sinuses of healthy subjects as well as in chronic sinusitis (CRS)
      patients. An infection is today rather seen as an imbalance between the commensal
      microbiome and the bacterial pathogens, resulting in a reduction in commensal
      bacterial diversity, combined with an increase in the growth of microbes
      eliciting an inflammatory response. This will in turn lead to the clinical
      symptoms of sinusitis. Probiotics (microorganisms that confer a health benefit)
      can be used either as a form of living antibiotics treatment, or as an immune
      modulatory intervention. Topical probiotics, which is the focus of this review,
      have shown efficacy in a limited number of trials in otitis media and
      tonsillitis, but to date not in CRS. Although bacterial interference capacity
      against pathogens can be determined in in vitro experiments, it may not translate
      to a health benefit. This limits the role of laboratory research in identifying
      probiotic strains with a clinical benefit. To gain more clinical experience
      without further delay, I recommend future research to focus on empirical clinical
      trials in well-defined CRS patient populations and study the underlying
      mechanisms in more detail once a clinical benefit has been established.

PMID- 29379771
TI  - Use of Mass Spectrometry to Screen Glycan Early Markers in Hepatocellular
      Carcinoma.
AB  - Association between altered glycosylation patterns and poor prognosis in cancer
      points glycans as potential specific tumor markers. Most proteins are
      glycosylated and functionally arranged on cell surface and extracellular matrix,
      mediating interactions and cellular signaling. Thereby, aberrant glycans may be
      considered a pathological phenotype at least as important as changes in protein
      expression for cancer and other complex diseases. As most serum glycoproteins
      have hepatic origin, liver disease phenotypes, such as hepatocellular carcinoma
      (HCC), may present altered glycan profile and display important modifications.
      One of the prominent obstacles in HCC is the diagnostic in advanced stages when
      patients have several liver dysfunctions, limiting treatment options and life
      expectancy. The characterization of glycomic profiles in pathological conditions
      by means of mass spectrometry (MS) may lead to the discovery of early diagnostic
      markers using non-invasive approaches. MS is a powerful analytical technique
      capable of elucidating many glycobiological issues and overcome limitations of
      the serological markers currently applied in clinical practice. Therefore, MS
      based glycomics of tumor biomarkers is a promising tool to increase early
      detection and monitoring of disease.

PMID- 29379773
TI  - Pseudomonas aeruginosa Takes a Multi-Target Approach to Achieve Junction Breach.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen which uses a number of
      strategies to cross epithelial and endothelial barriers at cell-cell junctions.
      In this review, we describe how the coordinated actions of P. aeruginosa's
      virulence factors trigger various molecular mechanisms to disarm the junctional
      gate responsible for tissue integrity.

PMID- 29379774
TI  - Differential Effects of Iron, Zinc, and Copper on Dictyostelium discoideum Cell
      Growth and Resistance to Legionella pneumophila.
AB  - Iron, zinc, and copper play fundamental roles in eucaryotes and procaryotes, and
      their bioavailability regulates host-pathogen interactions. For intracellular
      pathogens, the source of metals is the cytoplasm of the host, which in turn
      manipulates intracellular metal traffic following pathogen recognition. It is
      established that iron is withheld from the pathogen-containing vacuole, whereas
      for copper and zinc the evidence is unclear. Most infection studies in mammals
      have concentrated on effects of metal deficiency/overloading at organismal level.
      Thus, zinc deficiency or supplementation correlate with high risk of respiratory
      tract infection or recovery from severe infection, respectively. Iron, zinc, and
      copper deficiency or overload affects lymphocyte proliferation/maturation, and
      thus the adaptive immune response. Whether they regulate innate immunity at
      macrophage level is open, except for iron. The early identification in a mouse
      mutant susceptible to mycobacterial infection of the iron transporter Nramp1
      allowed dissecting Nramp1 role in phagocytes, from the social amoeba
      Dictyostelium to macrophages. Nramp1 regulates iron efflux from the phagosomes,
      thus starving pathogenic bacteria for iron. Similar studies for zinc or copper
      are scant, due to the large number of copper and zinc transporters. In
      Dictyostelium, zinc and copper transporters include 11 and 6 members,
      respectively. To assess the role of zinc or copper in Dictyostelium, cells were
      grown under conditions of metal depletion or excess and tested for resistance to
      Legionella pneumophila infection. Iron shortage or overload inhibited
      Dictyostelium cell growth within few generations. Surprisingly, zinc or copper
      depletion failed to affect growth. Zinc or copper overloading inhibited cell
      growth at, respectively, 50- or 500-fold the physiological concentration,
      suggesting very efficient control of their homeostasis, as confirmed by
      Inductively Coupled Plasma Mass Spectrometry quantification of cellular metals.
      Legionella infection was inhibited or enhanced in cells grown under iron shortage
      or overload, respectively, confirming a major role for iron in controlling
      resistance to pathogens. In contrast, zinc and copper depletion or excess during
      growth did not affect Legionella infection. Using Zinpyr-1 as fluorescent sensor,
      we show that zinc accumulates in endo-lysosomal vesicles, including phagosomes,
      and the contractile vacuole. Furthermore, we provide evidence for
      permeabilization of the Legionella-containing vacuole during bacterial
      proliferation.

PMID- 29379775
TI  - Helicobacter pylori-Induced HB-EGF Upregulates Gastrin Expression via the EGF
      Receptor, C-Raf, Mek1, and Erk2 in the MAPK Pathway.
AB  - Helicobacter pylori is associated with hypergastrinemia, which has been linked to
      the development of gastric diseases. Although the molecular mechanism is not
      fully understood, H. pylori is known to modulate the Erk pathway for induction of
      gastrin expression. Herein we found that an epidermal growth factor (EGF)
      receptor kinase inhibitor significantly blocked H. pylori-induced gastrin
      promoter activity, suggesting involvement of EGF receptor ligands. Indeed, H.
      pylori induced mRNA expression of EGF family members such as amphiregulin, EGF,
      heparin-binding EGF-like growth factor (HB-EGF), and transforming growth factor
      alpha. Of these, specific siRNA targeting of HB-EGF significantly blocked H.
      pylori-induced gastrin expression. Moreover, H. pylori induced HB-EGF ectodomain
      shedding, which we found to be a critical process for H. pylori-induced gastrin
      expression. Thus, we demonstrate a novel role for human mature HB-EGF in
      stimulating gastrin promoter activity during H. pylori infection. Further
      investigation using specific siRNAs targeting each isoform of Raf, Mek, and Erk
      elucidated that the mechanism underlying H. pylori-induced gastrin expression can
      be delineated as the sequential activation of HB-EGF, the EGF receptor, C-Raf,
      Mek1, and the Erk2 molecules in the MAPK pathway. Surprisingly, whereas Erk2 acts
      as a potent activator of gastrin expression, siRNA knockdown of Erk1 induced
      gastrin promoter activity, suggesting that Erk1 typically acts as a repressor of
      gastrin expression. Elucidation of the mechanism of gastrin modulation by HB-EGF
      mediated EGF receptor transactivation should facilitate the development of
      therapeutic strategies against H. pylori-related hypergastrinemia and
      consequently gastric disease development, including gastric cancers.

PMID- 29379776
TI  - Interaction of Coxiella burnetii Strains of Different Sources and Genotypes with
      Bovine and Human Monocyte-Derived Macrophages.
AB  - Most human Q fever infections originate from small ruminants. By contrast, highly
      prevalent shedding of Coxiella (C.) burnetii by bovine milk rarely results in
      human disease. We hypothesized that primary bovine and human monocyte-derived
      macrophages (MDM) represent a suitable in vitro model for the identification of
      strain-specific virulence properties at the cellular level. Twelve different C.
      burnetii strains were selected to represent different host species and multiple
      loci variable number of tandem repeat analysis (MLVA) genotypes. Infection
      efficiency and replication of C. burnetii were monitored by cell culture re
      titration and qPCR. Expression of immunoregulatory factors after MDM infection
      was measured by qRT-PCR and flow cytometry. Invasion, replication and MDM
      response differed between C. burnetii strains but not between MDMs of the two
      hosts. Strains isolated from ruminants were less well internalized than isolates
      from humans and rodents. Internalization of MLVA group I strains was lower
      compared to other genogroups. Replication efficacy of C. burnetii in MDM ranged
      from low (MLVA group III) to high (MLVA group IV). Infected human and bovine MDM
      responded with a principal up-regulation of pro-inflammatory cytokines such as IL
      1beta, IL-12, and TNF-alpha. However, MLVA group IV strains induced a pronounced
      host response whereas infection with group I strains resulted in a milder
      response. C. burnetii infection marginally affected polarization of MDM. Only one
      C. burnetii strain of MLVA group IV caused a substantial up-regulation of
      activation markers (CD40, CD80) on the surface of bovine and human MDM. The study
      showed that replication of C. burnetii in MDM and the subsequent host cell
      response is genotype-specific rather than being determined by the host species
      pointing to a clear distinction in C. burnetii virulence between the genetic
      groups.

PMID- 29379778
TI  - 3D Printing in Surgical Management of Double Outlet Right Ventricle.
AB  - Double outlet right ventricle (DORV) is a heterogeneous group of congenital heart
      diseases that require individualized surgical approach based on precise
      understanding of the complex cardiovascular anatomy. Physical 3-dimensional (3D)
      print models not only allow fast and unequivocal perception of the complex
      anatomy but also eliminate misunderstanding or miscommunication among imagers and
      surgeons. Except for those cases showing well-recognized classic surgical anatomy
      of DORV such as in cases with a typical subaortic or subpulmonary ventricular
      septal defect, 3D print models are of enormous value in surgical decision and
      planning. Furthermore, 3D print models can also be used for rehearsal of the
      intended procedure before the actual surgery on the patient so that the outcome
      of the procedure is precisely predicted and the procedure can be optimally
      tailored for the patient's specific anatomy. 3D print models are invaluable
      resource for hands-on surgical training of congenital heart surgeons.

PMID- 29379777
TI  - Many Genes-One Disease? Genetics of Nephronophthisis (NPHP) and NPHP-Associated
      Disorders.
AB  - Nephronophthisis (NPHP) is a renal ciliopathy and an autosomal recessive cause of
      cystic kidney disease, renal fibrosis, and end-stage renal failure, affecting
      children and young adults. Molecular genetic studies have identified more than 20
      genes underlying this disorder, whose protein products are all related to cilia,
      centrosome, or mitotic spindle function. In around 15% of cases, there are
      additional features of a ciliopathy syndrome, including retinal defects, liver
      fibrosis, skeletal abnormalities, and brain developmental disorders. Alongside,
      gene identification has arisen molecular mechanistic insights into the disease
      pathogenesis. The genetic causes of NPHP are discussed in terms of how they help
      us to define treatable disease pathways including the cyclic adenosine
      monophosphate pathway, the mTOR pathway, Hedgehog signaling pathways, and DNA
      damage response pathways. While the underlying pathology of the many types of
      NPHP remains similar, the defined disease mechanisms are diverse, and a
      personalized medicine approach for therapy in NPHP patients is likely to be
      required.

PMID- 29379779
TI  - Long-term Associations of an Early Corrected Ventricular Septal Defect and Stress
      Systems of Child and Mother at Primary School Age.
AB  - Introduction: Ventricular septal defect (VSD) is the most common congenital heart
      defect, with larger VSDs typically being corrected with an open-heart surgery
      during infancy. Long-term consequences of a VSD-corrective surgery on stress
      systems of child and mother are still unknown. The aim of the present study is to
      investigate the associations of an early corrected VSD and diurnal cortisol
      release of child and mother. Methods: 26 children (12 boys) between 6 and 9 years
      old, who underwent surgery for an isolated VSD within the first 3 years of life,
      and their mothers participated in the study. Their diurnal cortisol profiles were
      compared to a sex-, age-, and socioeconomic status-matched healthy control group.
      Within the VSD group, associations between cortisol and characteristics of
      surgery and hospitalization were investigated. Child and mother
      psychopathological symptoms were considered as a possible interfering mechanism
      of altered cortisol profiles. Results: Diurnal cortisol profiles of children with
      an early corrected VSD did not differ from those of controls. However, mothers of
      affected children exhibited higher cortisol levels in the morning (p < 0.001,
      [Formula: see text]) and a steeper diurnal cortisol slope (p = 0.016, [Formula:
      see text]) than mothers of healthy children. Conclusion: Results indicate a
      favorable development of children with an early corrected VSD, in terms of
      comparable diurnal cortisol profiles with healthy controls, according to a
      comparable mother-rated psychopathology. Mothers of affected children reveal
      altered diurnal cortisol levels, without differences in self-rated
      psychopathology. This divergence should be clarified in future research.

PMID- 29379781
TI  - Novel Highly Luminescent Amine-Functionalized Bridged Silsesquioxanes.
AB  - Amine-functionalized bridged silsesquioxanes (BSs) were synthesized from bis[(3
      trimethoxysilyl)propyl] amine via a solvent-mediated route. BS-1 and BS-2 were
      obtained at neutral pH with sub- and stoichiometric amounts of water,
      respectively, and high tetrahydrofuran content. BS-3 was prepared with
      hyperstoichiometric water concentration, high tetrahydrofuran content, and
      hydrochloric acid. BS-4 was synthesized with hyperstoichiometric water
      concentration, high ethanol content, and sodium hydroxide. BS-1 and BS-2 were
      produced as transparent films, whereas BS-3 and BS-4 formed white powders. Face
      to-face stacking of flat or folded lamellae yielded quasi-hydrophobic platelets
      with emission quantum yields of 0.05 +/- 0.01 (BS-1 and BS-2) or superhydrophilic
      onion-like nanoparticles with exciting emission quantum yields of 0.38 +/- 0.03
      (BS-3) and 0.33 +/- 0.04 (BS-4), respectively. The latter two values are the
      largest ever reported for amine-functionalized siloxane-based hybrids lacking
      aromatic groups. Fast Grotthus proton hopping between = [Formula: see text]/ = NH
      groups (BS-3) and = N-/ = NH groups (BS-4), promoted by H+ and OH- ions,
      respectively, and aided by short amine-amine contacts provided by the onion-like
      morphology, account for this unique optical behavior.

PMID- 29379780
TI  - Carbon-11 and Fluorine-18 Labeled Amino Acid Tracers for Positron Emission
      Tomography Imaging of Tumors.
AB  - Tumor cells have an increased nutritional demand for amino acids (AAs) to satisfy
      their rapid proliferation. Positron-emitting nuclide labeled AAs are interesting
      probes and are of great importance for imaging tumors using positron emission
      tomography (PET). Carbon-11 and fluorine-18 labeled AAs include the [1-11C] AAs,
      labeling alpha-C- AAs, the branched-chain of AAs and N-substituted carbon-11
      labeled AAs. These tracers target protein synthesis or amino acid (AA) transport,
      and their uptake mechanism mainly involves AA transport. AA PET tracers have been
      widely used in clinical settings to image brain tumors, neuroendocrine tumors,
      prostate cancer, breast cancer, non-small cell lung cancer (NSCLC) and
      hepatocellular carcinoma. This review focuses on the fundamental concepts and the
      uptake mechanism of AAs, AA PET tracers and their clinical applications.

PMID- 29379782
TI  - Delayed Influence of Spinal Cord Injury on the Amino Acids of NO* Metabolism in
      Rat Cerebral Cortex Is Attenuated by Thiamine.
AB  - Severe spinal cord injuries (SCIs) result in chronic neuroinflammation in the
      brain, associated with the development of cognitive and behavioral impairments.
      Nitric oxide (NO*) is a gaseous messenger involved in neuronal signaling and
      inflammation, contributing to nitrosative stress under dysregulated production of
      reactive nitrogen species. In this work, biochemical changes induced in the
      cerebral cortex of rats 8 weeks after SCI are assessed by quantification of the
      levels of amino acids participating in the NO* and glutathione metabolism. The
      contribution of the injury-induced neurodegeneration is revealed by comparison of
      the SCI- and laminectomy (LE)-subjected animals. Effects of the operative
      interventions are assessed by comparison of the operated (LE/SCI) and non
      operated animals. Lower ratios of citrulline (Cit) to arginine (Arg) or Cit to
      ornithine and a more profound decrease in the ratio of lysine to glycine
      distinguish SCI animals from those after LE. The data suggest decreased NO*
      production from both Arg and homoarginine in the cortex 8 weeks after SCI. Both
      LE and SCI groups show a strong decrease in the level of cortex glutathione. The
      neurotropic, anti-inflammatory, and antioxidant actions of thiamine (vitamin B1)
      prompted us to study the thiamine effects on the SCI-induced changes in the NO*
      and glutathione metabolism. A thiamine injection (400 mg/kg intraperitoneally)
      within 24 h after SCI abrogates the changes in the cerebral cortex amino acids
      related to NO*. Thiamine-induced normalization of the brain glutathione levels
      after LE and SCI may involve increased supply of glutamate for glutathione
      biosynthesis. Thus, thiamine protects from sequelae of SCI on NO*-related amino
      acids and glutathione in cerebral cortex.

PMID- 29379783
TI  - Pulmonary Eosinophilic Inflammatory Infiltration Post-Intensive Care in a Nearly
      Drowned Young Man with Papillary Fibroelastoma: A Rare Complication Discovered by
      Forensic Autopsy.
AB  - Papillary fibroelastoma is a rare benign lesion of heart (1). It is the second
      most common primary cardiac neoplasm, accounting for 4.4-8% of all tumors of the
      heart (2). We described a forensic autopsy of a nearly drowned young man with
      cardiac papillary fibroelastoma who died because of a pulmonary inflammatory
      infiltration rich in granulocytes after intensive care. This occurrence is rare
      but possible and should be kept in mind because a lung inflammatory infiltrate
      rich in eosinophilic granulocytes can be present in different pathological
      conditions and differential diagnoses are often difficult to do.

PMID- 29379786
TI  - Posterior Tracheopexy for Severe Tracheomalacia Associated with Esophageal
      Atresia (EA): Primary Treatment at the Time of Initial EA Repair versus Secondary
      Treatment.
AB  - Purpose: We review outcomes of posterior tracheopexy for tracheomalacia in
      esophageal atresia (EA) patients, comparing primary treatment at the time of
      initial EA repair versus secondary treatment. Methods: All EA patients who
      underwent posterior tracheopexy from October 2012 to September 2016 were
      retrospectively reviewed. Clinical symptoms, tracheomalacia scores, and
      persistent airway intrusion were collected. Indication for posterior tracheopexy
      was the presence of clinical symptoms, in combination with severe tracheomalacia
      as identified on bronchoscopic evaluation, typically defined as coaptation in one
      or more regions of the trachea. Secondary cases were usually those with chronic
      respiratory symptoms who underwent bronchoscopic evaluation, whereas primary
      cases were those found to have severe tracheomalacia on routine preoperative
      dynamic tracheobronchoscopy at the time of initial EA repair. Results: A total of
      118 patients underwent posterior tracheopexy: 18 (15%) primary versus 100 (85%)
      secondary cases. Median (interquartile range) age was 2 months (1-4 months) for
      primary (22% type C) and 18 months (8-40 months) for secondary (87% type C) cases
      (p < 0.001). There were statistically significant improvements in most clinical
      symptoms postoperatively for primary and secondary cases, with no significant
      differences in any postoperative symptoms between the two groups (p > 0.1). Total
      tracheomalacia scores improved significantly in primary (p = 0.013) and secondary
      (p < 0.001) cases. Multivariable Cox regression analysis indicated no differences
      in persistent airway intrusion requiring reoperation between primary and
      secondary tracheopexy adjusting for imbalances in age and EA type (p = 0.67).
      Conclusion: Posterior tracheopexy is effective in treating severe tracheomalacia
      with significant improvements in clinical symptoms and degree of airway collapse
      on bronchoscopy. With no significant differences in outcomes between primary and
      secondary treatment, posterior tracheopexy should be selectively considered at
      the time of initial EA repair.

PMID- 29379785
TI  - Eosinophilic Gastrointestinal Disorders Pathology.
AB  - Eosinophilic gastrointestinal disorders (EGID) are characterized pathologically
      by excess eosinophils in mucosal biopsies of one or multiple sites in the
      gastrointestinal (GI) tract, simultaneously or sequentially. Eosinophilic
      esophagitis (EoE) is the best characterized EGID, and in most patients it is an
      abnormal immune-mediated response to food antigens. Current recommendations for
      diagnosis include signs and symptoms of esophageal dysfunction that do not
      respond to proton-pump inhibitor therapy, and esophageal biopsies that exhibit at
      least 15 intraepithelial eosinophils in at least one high power field (HPF).
      Therapy consists of swallowed glucocorticoids or dietary elimination.
      Eosinophilic gastritis (EG) is the second most common form of EGID, but like all
      forms of EGID except EoE consensus recommendations for either clinical or
      pathological diagnosis do not exist. EG may be associated clinically with
      peripheral blood eosinophilia, hypoalbuminemia, and anemia, and pathologically
      with marked expansion of lamina propria by dense eosinophilic infiltrates.
      Eosinophilic enteritis (EE) may be subdivided into eosinophilic duodenitis,
      eosinophilic jejunitis, and eosinophilic ileitis. Most investigators believe that
      EE rarely, if ever, exists as a solitary form of EGID and is encountered only in
      patients who have at least one other affected portion of the GI tract.
      Eosinophilic colitis (EC) is perhaps the most enigmatic EGID. Distinction of EC
      from inflammatory bowel disease may be problematic especially in children.
      Multiple possible etiologies for EGID include hypereosinophilic syndrome, drug
      reactions, etc. Currently, the only etiology that can be identified
      histologically is parasitic infestation, if a portion of an invasive parasite is
      found in mucosal biopsies. This review will provide guidelines for the pathologic
      diagnosis of the various forms of EGID.

PMID- 29379784
TI  - Patient-Reported Outcomes in Patients with Chronic Kidney Disease and Kidney
      Transplant-Part 1.
AB  - Chronic kidney disease (CKD) is a complex medical condition that is associated
      with several comorbidities and requires comprehensive medical management. Given
      the chronic nature of the condition, its frequent association with psychosocial
      distress, and its very significant symptom burden, the subjective patient
      experience is key toward understanding the true impact of CKD on the patients'
      life. Patient-reported outcome measures are important tools that can be used to
      support patient-centered care and patient engagement during the complex
      management of patients with CKD. The routine collection and use of patient
      reported outcomes (PROs) in clinical practice may improve quality of care and
      outcomes, and may provide useful data to understand the disease from both an
      individual and a population perspective. Many tools used to measure PROs focus on
      assessing health-related quality of life, which is significantly impaired among
      patients with CKD. Health-related quality of life, in addition to being an
      important outcome itself, is associated with clinical outcomes such as health
      care use and mortality. In Part 1 of this review, we provide an overview of PROs
      and implications of their use in the context of CKD. In Part 2, we will review
      the selection of appropriate measures and the relevant domains of interest for
      patients with CKD.

PMID- 29379787
TI  - Computational Study of PCSK9-EGFA Complex with Effective Polarizable Bond Force
      Field.
AB  - Inhibiting of Proprotein Convertase Subtilisin/Kexin-type 9 (PCSK9) and Low
      Density Lipoprotein Receptor (LDLR) binding is an effective way for reducing Low
      Density Lipoprotein cholesterol (LDL-C). Understanding the interaction between
      PCSK9 and LDLR is useful for PCSK9 inhibitor design. In this work, MD simulations
      with the standard (non-polarizable) AMBER force field and effective polarizable
      bond (EPB) force field were performed for wild type and four mutants of PCSK9 and
      EGFA (Epidermal Growth Factor-like repeat A) domain of LDLR complexes. These four
      mutants are gain-of-function mutants. The analysis of hydrogen bond dynamics and
      the relative binding free energy indicates that EPB is more reliable in
      simulating protein dynamics and predicting relative binding affinity. Structures
      sampled from MD simulations with the standard AMBER force field deviate too far
      away from crystal structures. Many important interaction components between of
      PCSK9 and EGFA no longer exist in the simulation with the Amber force field. For
      comparison, simulation using EPB force field gives more stable structures as
      shown by hydrogen bond analysis and produced relative binding free energies that
      are consistent with experimental results. Our study suggests that inclusion of
      polarization effects in MD simulation is important for studying the protein
      protein interaction.

PMID- 29379788
TI  - Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis.
AB  - Efficient clearance of apoptotic cells, termed efferocytosis, critically
      regulates normal homeostasis whereas defective uptake of apoptotic cells results
      in chronic and non-resolving inflammatory diseases, such as advanced
      atherosclerosis. Monocyte-derived macrophages recruited into developing
      atherosclerotic lesions initially display efficient efferocytosis and temper
      inflammatory responses, processes that restrict plaque progression. However,
      during the course of plaque development, macrophages undergo cellular
      reprogramming that reduces efferocytic capacity, which results in post-apoptotic
      necrosis of apoptotic cells and inflammation. Furthermore, defective
      efferocytosis in advanced atherosclerosis is a major driver of necrotic core
      formation, which can trigger plaque rupture and acute thrombotic cardiovascular
      events. In this review, we discuss the molecular and cellular mechanisms that
      regulate efferocytosis, how efferocytosis promotes the resolution of
      inflammation, and how defective efferocytosis leads to the formation of
      clinically dangerous atherosclerotic plaques.

PMID- 29379789
TI  - Cathepsin S As an Inhibitor of Cardiovascular Inflammation and Calcification in
      Chronic Kidney Disease.
AB  - Cardiovascular disease (CVD) is responsible for the majority of deaths in the
      developed world. Particularly, in patients with chronic kidney disease (CKD), the
      imbalance of calcium and phosphate may lead to the acceleration of both vascular
      and valve inflammation and calcification. One in two patients with CKD are
      reported as dying from cardiovascular causes due to the resulting acceleration in
      the development of atherosclerosis plaques. In addition, CKD patients on
      hemodialysis are prone to aortic valve calcification and often need valve
      replacement before kidney transplantation. The lysosomal proteases, cathepsins,
      are composed of 11 cysteine members (cathepsin B, C, F, H, K, L, O, S, V, W, and
      Z), as well as serine proteases cathepsin A and G, which cleave peptide bonds
      with serine as the amino acid, and aspartyl proteases D and E, which use an
      activated water molecule bound to aspartate to break peptide substrate. Cysteine
      proteases, also known as thiol proteases, degrade protein via the deprotonation
      of a thiol and have been found to play a significant role in autoimmune disease,
      atherosclerosis, aortic valve calcification, cardiac repair, and cardiomyopathy,
      operating within extracellular spaces. This review sought to evaluate recent
      findings in this field, highlighting how among cathepsins, the inhibition of
      cathepsin S in particular, could play a significant role in diminishing the
      effects of CVD, especially for patients with CKD.

PMID- 29379790
TI  - Isolation, Identification, and Characterization of a New Highly Pathogenic Field
      Isolate of Mycobacterium avium spp. avium.
AB  - Avian tuberculosis is a chronic, contagious zoonotic disease affecting birds,
      mammals, and humans. The disease is most often caused by Mycobacterium avium spp.
      avium (MAA). Strain resources are important for research on avian tuberculosis
      and vaccine development. However, there has been little reported about the newly
      identified MAA strain in recent years in China. In this study, a new strain was
      isolated from a fowl with symptoms of avian tuberculosis by bacterial culture.
      The isolated strain was identified to be MAA by culture, staining, and
      biochemical and genetic analysis, except for different colony morphology. The
      isolated strain was Ziehl-Zeelsen staining positive, resistant to p-nitrobenzoic
      acid, and negative for niacin production, Tween-80 hydrolysis, heat stable
      catalase and nitrate production. The strain had the DnaJ gene, IS1245, and IS901,
      as well. Serum agglutination indicated that the MAA strain was of serotype 1. The
      MAA strain showed strong virulence via mortality in rabbits and chickens. The
      prepared tuberculin of the MAA strain had similar potency compared to the MAA
      reference strain and standard tuberculin via a tuberculin skin test. Our studies
      suggested that this MAA strain tends to be a novel subtype, which might enrich
      the strain resource of avian tuberculosis.

PMID- 29379791
TI  - MicroRNAs Encoded by Bovine Leukemia Virus (BLV) Are Associated with Reduced
      Expression of B Cell Transcriptional Regulators in Dairy Cattle Naturally
      Infected with BLV.
AB  - Bovine leukemia virus (BLV) is estimated to infect over 83% of dairy herds and
      over 40% of all dairy cows in the United States. While, BLV only causes leukemia
      in a small proportion of animals, research indicates that BLV+ cattle exhibit
      reduced milk production and longevity that is distinct from lymphoma development.
      It is hypothesized that BLV negatively affects production by interfering with
      cattle immunity and increasing the risk of secondary infections. In particular,
      BLV+ cows demonstrate reduced circulating levels of both antigen-specific and
      total IgM. This study investigated possible mechanisms by which BLV could
      interfere with the production of IgM in naturally infected cattle. Specifically,
      total plasma IgM and the expression of genes IGJ, BLIMP1, BCL6, and PAX5 in
      circulating IgM+ B cells were measured in 15 naturally infected BLV+ and 15 BLV-
      cows. In addition, BLV proviral load (PVL) (a relative measurement of BLV
      provirus integrated into host DNA) and the relative expression of BLV TAX and 5
      BLV microRNAs (miRNAs) were characterized and correlated to the expression of
      selected endogenous genes. BLV+ cows exhibited lower total plasma IgM and lower
      expression of IGJ, BLIMP1, and BCL6. While, BLV TAX and BLV miRNAs failed to
      correlate with IGJ expression, both BLV TAX and BLV miRNAs exhibited negative
      associations with BLIMP1 and BCL6 gene expression. The results suggest a possible
      transcriptional pathway by which BLV interferes with IgM production in naturally
      infected cattle.

PMID- 29379792
TI  - Pathogenesis of Mycobacterium bovis Infection: the Badger Model As a Paradigm for
      Understanding Tuberculosis in Animals.
AB  - Tuberculosis in animals is caused principally by infection with Mycobacterium
      bovis and the potential for transmission of infection to humans is often the
      fundamental driver for surveillance of disease in livestock and wild animals.
      However, with such a vast array of species susceptible to infection, it is often
      extremely difficult to gain a detailed understanding of the pathogenesis of
      infection--a key component of the epidemiology in all affected species. This is
      important because the development of disease control strategies in animals is
      determined chiefly by an understanding of the epidemiology of the disease. The
      most revealing data from which to formulate theories on pathogenesis are that
      observed in susceptible hosts infected by natural transmission. These data are
      gathered from detailed studies of the distribution of gross and histological
      lesions, and the presence and distribution of infection as determined by highly
      sensitive bacteriology procedures. The information can also be used to establish
      the baseline for evaluating experimental model systems. The European badger
      (Meles meles) is one of a very small number of wild animal hosts where detailed
      knowledge of the pathogenesis of M. bovis infection has been generated from
      observations in natural-infected animals. By drawing parallels from other animal
      species, an experimental badger infection model has also been established where
      infection of the lower respiratory tract mimics infection and the disease
      observed in natural-infected badgers. This has facilitated the development of
      diagnostic tests and testing of vaccines that have the potential to control the
      disease in badgers. In this review, we highlight the fundamental principles of
      how detailed knowledge of pathogenesis can be used to evaluate specific
      intervention strategies, and how the badger model may be a paradigm for
      understanding pathogenesis of tuberculosis in any affected wild animal species.

PMID- 29379793
TI  - Effect of Gegen Qinlian Decoction on Cardiac Gene Expression in Diabetic Mice.
AB  - The aim of this research is to investigate the therapeutic effect of GGQL
      decoction on cardiac dysfunction and elucidate the pharmacological mechanisms.
      db/db mice were divided into DB group or GGQL group, and WT mice were used as
      control. All mice were accessed by echocardiography. And the total RNA of LV
      tissue samples was sequenced, then differential expression genes were analyzed.
      The RNA-seq results were validated by the results of RT-qPCR of 4 genes
      identified as differentially expressed. The content of pyruvate and ceramide in
      myocardial tissue was also measured. The results showed that GGQL decoction could
      significantly improve the diastolic dysfunction, increase the content of
      pyruvate, and had the trend to reduce the ceramide content. The results of RNA
      seq showed that 2958 genes were differentially expressed when comparing the DB
      group with the WT group. Among them, compared with the DB group, 26 genes were
      differentially regulated in the GGQL group. The expression results of 4 genes
      were consistent with the RNA-seq results. Our study reveals that GGQL decoction
      has a therapeutic effect on diastolic dysfunction of the left ventricular and the
      effect may be related to its role in promoting myocardial glycolysis and
      decreasing the content of ceramide.

PMID- 29379794
TI  - New Targets for Zika Virus Determined by Human-Viral Interactomic: A
      Bioinformatics Approach.
AB  - Identifying ZIKV factors interfering with human host pathways represents a major
      challenge in understanding ZIKV tropism and pathogenesis. The integration of
      proteomic, gene expression and Protein-Protein Interactions (PPIs) established
      between ZIKV and human host proteins predicted by the OralInt algorithm
      identified 1898 interactions with medium or high score (>=0.7). Targets
      implicated in vesicular traffic and docking were identified. New receptors
      involved in endocytosis pathways as ZIKV entry targets, using both clathrin
      dependent (17 receptors) and independent (10 receptors) pathways, are described.
      New targets used by the ZIKV to undermine the host's antiviral immune response
      are proposed based on predicted interactions established between the virus and
      host cell receptors and/or proteins with an effector or signaling role in the
      immune response such as IFN receptors and TLR. Complement and cytokines are
      proposed as extracellular potential interacting partners of the secreted form of
      NS1 ZIKV protein. Altogether, in this article, 18 new human targets for
      structural and nonstructural ZIKV proteins are proposed. These results are of
      great relevance for the understanding of viral pathogenesis and consequently the
      development of preventive (vaccines) and therapeutic targets for ZIKV infection
      management.

PMID- 29379795
TI  - Epithelial-Mesenchymal Transition in Pancreatic Cancer: A Review.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid
      malignancies and is characterized by its insensitivity to current therapy. The
      invasion and metastasis of solid tumors such as PDAC are complex processes
      involving many factors. Recent insights into the role of cancer stem cells (CSCs)
      and the epithelial-mesenchymal transition (EMT) in tumorigenesis have increased
      the knowledge base and highlighted new therapeutic targets of this disease. The
      process of EMT is regulated by a complex network of cytokines, transcription
      factors, growth factors, signaling pathways, and the tumor microenvironment,
      exhibiting CSC-like properties. The transition of solid cancer cells from an
      epithelial to a mesenchymal phenotype increases their migratory and invasive
      properties, thus promoting metastasis. In PDAC, the exact influence of EMT on the
      biological behaviors of cancer cells and its impact on clinical therapy remain
      controversial, but the therapeutic strategy of combining EMT inhibition with
      chemotherapy deserves attention. Alternatively, anti-inflammatory therapy that
      targets the interaction between inflammation and EMT is a valid strategy for
      treating the premalignant stage of tumor progression. In this review, we
      summarize the latest research on EMT and the potential relationship between EMT
      and PDAC.

PMID- 29379796
TI  - Tracking the Origin and Deciphering the Phylogenetic Relationship of Porcine
      Epidemic Diarrhea Virus in Ecuador.
AB  - In 2010, new Chinese strains of porcine epidemic diarrhea virus (PEDV),
      clinically more severe than the classical strains, emerged. These strains were
      spread to United States in 2013 through an intercontinental transmission from
      China with further spreading across the world, evidencing the emergent nature of
      these strains. In the present study, an analysis of PEDV field sequences from
      Ecuador was conducted by comparing all the PEDV S gene sequences available in the
      GenBank database. Phylogenetic comparisons and Bayesian phylogeographic inference
      based on complete S gene sequences were also conducted to track the origin and
      putative route of PEDV. The sequence from the PED-outbreak in Ecuador was grouped
      into the clade II of PEDV genogroup 2a together with other sequences of isolates
      from Mexico, Canada, and United States. The phylogeographic study revealed the
      emergence of the Chinese PEDV strains, followed by spreading to US in 2013, from
      US to Korea, and later the introduction of PEDV to Canada, Mexico, and Ecuador
      directly from the US. The sources of imports of live swine in Ecuador in 2014
      were mainly from Chile and US. Thus, this movement of pigs is suggested as the
      main way for introducing PEDV to Ecuador.

PMID- 29379797
TI  - Detection and Characterization of Hepatitis E Virus in Goats at Slaughterhouse in
      Tai'an Region, China.
AB  - Background: Hepatitis E virus (HEV) is a significant pathogen of viral hepatitis
      and can be transmitted through fecal-oral route. Epidemiological data concerning
      HEV in goats, however, are relatively sparse to date. Here, the prevalence and
      characteristics of HEV isolated from goats at slaughterhouse were investigated in
      Tai'an region, China. Methods: Anti-HEV immunoglobulin G (IgG) in blood samples
      and HEV RNA in the liver samples were determined by using an enzyme-linked
      immunosorbent assay (ELISA) and a nested reverse transcription polymerase chain
      reaction (RT-PCR), respectively. In addition, partial nucleotide sequences of
      open reading frame 2 (ORF-2) of HEV isolates were analyzed. Results: Fifty goat
      blood samples (46.7%, 50/120) were masculine for anti-HEV IgG. HEV RNA was
      detected in 2 liver samples (4.0%, 2/50) and belonged to genotype 4 subtype 4 h,
      with high identity (91.2-93%) with cow HEV strains detected in the same province,
      China. Conclusions: These findings demonstrated that goats may be an important
      reservoir for HEV and can become a major source of HEV infection in humans via
      food chain.

PMID- 29379798
TI  - Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia
      on Chronic Inflammatory Pain in Mice.
AB  - Chronic inflammatory pain may result from peripheral tissue injury or
      inflammation, increasing the release of protons, histamines, adenosine
      triphosphate, and several proinflammatory cytokines and chemokines. Transient
      receptor potential vanilloid 1 (TRPV1) is known to be involved in acute to
      subacute neuropathic and inflammatory pain; however, its exact mechanisms in
      chronic inflammatory pain are not elucidated. Our results showed that EA
      significantly reduced chronic mechanical and thermal hyperalgesia in the chronic
      inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also
      abolished in TRPV1-/- mice. TRPV1 increased in the dorsal root ganglion (DRG) and
      spinal cord (SC) at 3 weeks after CFA injection. The expression levels of
      downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of
      pERK, pp38, and pJNK. Transcription factors (pCREB and pNFkappaB) and nociceptive
      ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory
      mediators such as GFAP, S100B, and RAGE were also involved. The expression levels
      of these molecules were reduced in EA and TRPV1-/- mice but not in the sham EA
      group. Our data provided evidence to support the clinical use of EA for treating
      chronic inflammatory pain.

PMID- 29379800
TI  - Lateral Ramus Cortical Bone Plate in Alveolar Cleft Osteoplasty with Concomitant
      Use of Buccal Fat Pad Derived Cells and Autogenous Bone: Phase I Clinical Trial.
AB  - Tissue regeneration has become a promising treatment for craniomaxillofacial bone
      defects such as alveolar clefts. This study sought to assess the efficacy of
      lateral ramus cortical plate with buccal fat pad derived mesenchymal stem cells
      (BFSCs) in treatment of human alveolar cleft defects. Ten patients with
      unilateral anterior maxillary cleft met the inclusion criteria and were assigned
      to three treatment groups. First group was treated with anterior iliac crest
      (AIC) bone and a collagen membrane (AIC group), the second group was treated with
      lateral ramus cortical bone plate (LRCP) with BFSCs mounted on a natural bovine
      bone mineral (LRCP+BFSC), and the third group was treated with AIC bone, BFSCs
      cultured on natural bovine bone mineral, and a collagen membrane (AIC+BFSC). The
      amount of regenerated bone was measured using cone beam computed tomography 6
      months postoperatively. AIC group showed the least amount of new bone formation
      (70 +/- 10.40%). LRCP+BFSC group demonstrated defect closure and higher amounts
      of new bone formation (75 +/- 3.5%) but less than AIC+BFSC (82.5 +/- 6.45%),
      suggesting that use of BFSCs within LRCP cage and AIC may enhance bone
      regeneration in alveolar cleft bone defects; however, the differences were not
      statistically significant. This clinical trial was registered at
      clinicaltrial.gov with NCT02859025 identifier.

PMID- 29379799
TI  - Diabetes Mellitus and Risk of Hepatocellular Carcinoma.
AB  - The occurrence of hepatocellular carcinoma (HCC) is two to three times higher in
      patients with diabetes mellitus (DM), the prevalence of which is increasing
      sharply worldwide. The purpose of this review was to describe clinical links
      between DM and HCC and potential biological mechanisms that may account for this
      association. We evaluated the role of potential pathways that could account for
      the development of HCC with different etiologies in the presence of DM. In
      addition, we also briefly discuss the potential effect of other factors such as
      type and dosage of antidiabetic medicines and duration of DM on HCC risk.

PMID- 29379801
TI  - Quercetin Improves Glucose and Lipid Metabolism of Diabetic Rats: Involvement of
      Akt Signaling and SIRT1.
AB  - Glucose and lipid metabolism disorder in diabetes mellitus often causes damage to
      multiple tissues and organs. Diabetes mellitus is beneficially affected by
      quercetin. However, its concrete mechanisms are yet to be fully elucidated. In
      our study, diabetes was induced in Sprague-Dawley rats by STZ injection. The rats
      were randomly divided into normal control, diabetic model, low-dose quercetin
      treatment, high-dose quercetin treatment, and pioglitazone treatment groups.
      Fasting blood glucose was collected to evaluate diabetes. Immunohistochemistry
      and fluorometric assay were performed to explore SIRT1. Akt levels were measured
      through immunoprecipitation and Western blot. After 12 weeks of quercetin
      treatment, the biochemical parameters of glucose and lipid metabolism improved to
      varying degrees. Hepatic histomorphological injury was alleviated, and hepatic
      glycogen content was increased. The expression and activity of hepatic SIRT1 were
      enhanced, and Akt was activated by phosphorylation and deacetylation. These
      results suggested that the beneficial effects of quercetin on glucose and lipid
      metabolism disorder are probably associated with the upregulated activity and
      protein level of SIRT1 and its influence on Akt signaling pathway. Hence,
      quercetin shows potential for the treatment of glucose and lipid metabolism
      disorder in diabetes mellitus.

PMID- 29379803
TI  - Delayed Cardiac Rupture Induced by Traumatic Myocardial Infarction: Consequence
      of a 45-Magnum Blast Injury; A Comprehensive Case Review.
AB  - A penetrating chest trauma, a myocardial contusion or a myocardial infarction can
      lead to a cardiac rupture, which is linked to an extreme high death rate. Only
      few cases with delayed perforation of the myocardium have been reported in
      literature. We report about a penetrating gunshot injury, which led to a
      myocardial contusion with secondary delayed rupture of the left ventricle and the
      left inferior lobe of the lung. The leakage of the lesion in the left ventricle
      could be sealed sufficiently with fibrin-coated collagen fleeces after adapting
      stitches with Prolene 2-0. For additional stabilization of the vulnerable
      myocardium area, a bovine patch has been placed on the damaged ventricle. Fibrin
      fleeces are used successfully in cardiac surgery, as in our case, to seal the
      leakage of the lesion in the left ventricle. The implantation of a bovine patch
      in the pericardium could prevent a cardiac compartment syndrome with a fatal
      pericardial tamponade. To prohibit a thoracic compartment syndrome a modified
      Bogota bag could be sewed in for temporarily closure of the chest. In most cases
      penetrating cardiac injuries can be treated without heart-lung-machines. An
      immediate transfer to a cardio-surgical center is, due to the acute situation,
      not possible. If a surgeon with thoraco-surgical expertise is present a transfer
      is not absolutely necessary.

PMID- 29379802
TI  - Inflammatory Cytokine Signaling during Development of Pancreatic and Prostate
      Cancers.
AB  - Inflammation is essential for many diseases including cancer. Activation and
      recruitment of immune cells during inflammation result in a cytokine- and
      chemokine-enriched cell environment, which affects cancer development. Since each
      type of cancer has its unique tumor environment, effects of cytokines from
      different sources such as tumor-infiltrating immune cells, stromal cells,
      endothelial cells, and cancer cells on cancer development can be quite complex.
      In this review, how immune cells contribute to tumorigenesis of pancreatic and
      prostate cancers through their secreted cytokines is discussed. In addition, the
      cytokine signaling that tumor cells of pancreatic and prostate cancers utilize to
      benefit their own survival is delineated.

PMID- 29379804
TI  - Effects of Aloe Vera and Chitosan Nanoparticle Thin-Film Membranes on Wound
      Healing in Full Thickness Infected Wounds with Methicillin Resistant
      Staphylococcus Aureus.
AB  - Objective: To assess effect of Aleo vera with chitosan nanoparticle biofilm on
      wound healing in full thickness infected wounds with antibiotic resistant gram
      positive bacteria. Method: Thirty rats were randomized into five groups of six
      rats each. Group I: Animals with uninfected wounds treated with 0.9% saline
      solution. Group II: Animals with infected wounds treated with saline. Group III:
      Animals with infected wounds were dressed with chitosan nanoparticle thin-film
      membranes. Group IV: Animals with infected wounds were treated topically with
      Aloe vera and Group V: Animals with infected wounds were treated topically with
      Aloe vera and dressed with chitosan nanoparticle thin-film membranes. Wound size
      was measured on 6, 9, 12, 15, 18 and 21days after surgery. Results: Microbiology,
      reduction in wound area and hydroxyproline contents indicated that there was
      significant difference (p<0.05) between group V and other groups. Quantitative
      histological studies and mean rank of the qualitative studies demonstrated that
      there was significant difference (p<0.05) between group V and other groups.
      Conclusion: The Aloe vera with chitosan nanoparticle thin-film membranes had a
      reproducible wound healing potential and hereby justified its use in practice.

PMID- 29379805
TI  - Descriptive Analysis of Right and Left-sided Traumatic Diaphragmatic Injuries;
      Case Series from a Single Institution.
AB  - Objective: To investigate the presentation, management and outcomes of left and
      right-sided traumatic diaphragmatic injury (TDI) in a single level I trauma
      center. Methods: This cross-sectional study was conducted during a 7-year period
      from 2008 to 2015 in a level I trauma center in Qatar. We included all the
      patients who presented with TDIs during the study period. Data included
      demographics, mechanism of injury, associated injuries, initial vitals, emergency
      department disposition, length of ICU and hospital stay, ventilator days,
      management, and outcomes. The variables were analyzed and compared for patients
      with left (LTDI) and right (RTDI). Results: A total of 52 TDI cases (79% LTDI and
      21% RTDI) were identified with a mean age of 31+/-11. LTDI patients were more
      likely to have higher Injury severity scores (p=0.50) and greater AAST organ
      injury scoring (p=0.661 for all) than RTDI patients. Surgical repair was
      performed for 85% LTDI vs. 73% RTDI (p=0.342). Recurrent DIs was reported only in
      LTDI (5.1% vs. 0.0%; p=0.911). Twelve patients died (9 LTDI and 3 RTDI), of them
      5 had associated head injury. Conclusion: This single-institution study confirms
      that LTDI are more commonly diagnosed than RTDI. Exploratory laparotomy is the
      most frequent procedure considered for the management of diaphragmatic injuries
      in the emergency settings. To improve outcomes in patients presenting with TDI,
      large prospective multicenter studies are needed to standardize the TDI
      management protocols including the diagnostic workup, timing of surgical
      intervention, and the most appropriate approach of treatment.

PMID- 29379806
TI  - The Predictive Value of Repeated Abdominal Ultrasonography in Patients with
      Multiple Trauma and Decreased Level of Consciousness: The Experience of a
      Resource-Limited Centre.
AB  - Objective: To determine the predictive value of repeated abdominal
      ultrasonography in patients with multiple trauma and decreased level of
      consciousness (LOC). Methods: This prospective cross-sectional study was
      conducted over a six-month period at Shahid Rajaee Trauma Hospital, Shiraz, Iran.
      We included hemodynamically stable blunt abdominal trauma patients with a
      decreased LOC (Glasgow Coma Scale <= 13) who were referred to the neurosurgery
      ICU ward. Included cases underwent 1 contrast-enhanced CT scan and two-time
      ultrasonographic study of the abdomen with an interval of 48 hours. The
      diagnostic accuracy of the ultrasonography was determined according to the CT
      scan results. Results: Overall 80 patients with mean age of 37.75 +/- 18.67 years
      were included. There were 17 (21.3%) women and 63 (78.8%) men among the patients.
      Compared with the CT-Scan, the first ultrasonography showed a sensitivity of 60%,
      specificity of 80%, PPV of 16.60%, NPV of 96.80%, and a diagnostic accuracy of
      70%. The same values for the second ultrasonographic study were 80%, 79%, 20%,
      98%, and 79%, respectively. In 4 (5%) patients whose first ultrasonography and CT
      scan results were negative, the second ultrasonography was positive for injury.
      Conclusion: In patients with blunt trauma to the abdomen, when the only
      indication of abdominal CT scan is a decreased LOC, two ultrasonographic studies
      can replace a CT imaging.

PMID- 29379807
TI  - Efficacy and Safety of Morphine and Low Dose Ketamine for Pain Control of
      Patients with Long Bone Fractures: A Randomized, Double-Blind, Clinical Trial.
AB  - Objective: To compare the effects of intravenous morphine and a low dose of
      ketamine on pain intensity of patients with traumatic fractures of the long
      bones. Methods: This randomized, controlled, double-blinded, clinical trial was
      conducted in the adult emergency department (ED) of Emam Khomeini hospital, a
      tertiary general hospital affiliated with Mazandaran University of Medical
      Sciences, in Northern Iran, during a 6-month period. Patients were randomly
      assigned to receive intravenous morphine (0.1 mg/kg) or low dose ketamine (0.5
      mg/kg) for control of the pain in the emergency room. The pain intensity was
      checked by a nurse using the visual analogue scale (VAS) at 30, 60, 90, 120, 180
      and 240, minutes after the intervention. Results: Overall we included a total
      number of 156 patients with mean age of 35.87+/-3.38 years. There were 111
      (71.2%) men and 4 (28.8%) women among the patients. Patients were randomly
      assigned to receive intravenous morphine (n=78) or low dose ketamine (n=78). The
      pain intensity decreased significantly in both study groups after 240 minutes of
      intervention. However, there was no significant difference between the two study
      groups regarding the pain intensity at 30 (p=0.378), 60 (p=0.927), 90 (p=0.434),
      120 (p=0.557), 180 (p=0.991) and 240 (p=0.829) minutes. The side effects were
      comparable while low dose ketamine was associated with higher need for rescue
      analgesic (p=0.036). Conclusion: The results of the current study demonstrates
      that the intravenous low dose ketamine leads to successful pain control in
      patients with long bone fractures and the effects are comparable with intravenous
      morphine.

PMID- 29379808
TI  - Outcome after Surgical Management of Acetabular Fractures: A 7-Year Experience.
AB  - Objective: To determine the functional and radiologic results of surgical
      treatment in patients with acetabular fractures. Methods: This was a
      retrospective cross-sectional study. We retrospectively reviewed medical records
      of patients operatively treated acute acetabular fractures at a level I trauma
      center (Shahid Rajaee) and an orthopedic center (Shahid Chamran) both in southern
      Iran (Shiraz) with minimally 1 year follow up over a period of 7 years from April
      2009 to March 2016. Functional and radiographic outcomes, and complication were
      considered as main outcomes. Results: A total number of 79 patients completed the
      study. Fifty-five patients were operated through Kocher-Langenbeck approach, and
      18 were operated through the standard ilioinguinal approach, and 6 patients were
      operated through the standard ilioinguinal approach combined with Kocher
      Langenbeck approach. The mean follow-up of patients was 45.6 months. The average
      operative time was 162.4+/-78.5 min, and the median blood loss was 500 ml.
      Functional results were excellent in 41 patients (51.9%), good in 12 (15.2%),
      fair in 13 (16.5%), and poor in 13 patients (16.5%). Radiologic results were
      excellent in 27 cases (34.2%), good in 17 cases (21.5%), fair in 18 cases
      (22.8%), and poor in 16 (16.5%). Osteoarthritis of hip (60.8%) and AVN of head of
      femur (22.8%) were two most common complications. In addition, there wasn't any
      significant difference between surgical approaches regarding clinical and
      radiographic outcomes. Conclusion: The operative treatment for acetabular
      fractures gives universally satisfactory results. Thereafter, this study provides
      evidence that ilioinguinal approach is a good choice for anterior fractures,
      Kocher-Langenbeck is a good choice for posteriors fractures, and combined
      approach may be a good choice in the management of acetabular fractures involving
      two columns.

PMID- 29379809
TI  - Epidemiology and Pattern of Traumatic Brain Injury in a Developing Country
      Regional Trauma Center.
AB  - Objective: To determine the epidemiological aspects of patients with traumatic
      brain injury (TBI) in a regional trauma center. Methods: A cross-sectional study
      was conducted on patients with TBI during 2013 to 2016 in a single center in
      Hamedan, central Iran. The distribution and relationships of TBI was assessed
      with gender, age, type of trauma, traumatic cause, exiting status and Length of
      Hospitalization (LOH). Data were analyzed by Stata V11 statistical software.
      Results: In general, 9426 patients with TBI were enrolled in analyses. The mean
      +/- SD age of patients was 29.70 (+/- 21.46) years. Multivariate logistic
      regression indicated that being male [OR: 1.29; 95% CI (2.92-4.73), P <=0.001],
      41-50 to 71-80 and 90+ years old' age groups (1.32<OR<3.12, 0.029<p<=0.001),
      having surgery [OR: 5.58; 95% CI (4.89-6.37), p<=0.001], and different types of
      trauma (p<=0.001) were significantly related to LOH. Moreover, odds ratio of
      mortality was 1.52 times greater in males than females (p<=0.001). As the age
      increases, the odds ratio of mortality was also rising. However, having surgery
      [OR: 3.72; 95% CI (2.92-4.73), p<=0.001], LOH >5 days [OR: 2.01; 95% CI (1.60
      2.52), p<=0.001] and different types of trauma were significantly related to
      mortality. Conclusion: TBI is one of the main causes of mortality and LOH of the
      young population. By providing preventive measures and a traumatic care system,
      the burden of trauma can be greatly reduced, the implementation of the trauma
      care system in Hamedan province is a necessity.

PMID- 29379810
TI  - The Frequency of Brain CT-Scan Findings in Patients with Scalp Lacerations
      Following Mild Traumatic Brain Injury; A Cross-Sectional Study.
AB  - Objective: To determine the frequency of the brain CT-scan findings in patients
      with mild traumatic brain injury (TBI) and scalp lacerations. Methods: This cross
      sectional study was conducted during a 1-year period from March 2016 to March
      2017 in Level I trauma center in Shiraz, Southern Iran. We included all the adult
      patients (>=18 years) admitted to our emergency room with mild TBI (GCS on
      admission of 15) and scalp lacerations. All the patients underwent Brain CT-Scan
      and the scans were reviewed by two radiologists who were unaware of the patients'
      clinical findings. The results are reported as proportions and frequencies.
      Results: Overall we included a total number of 94 patients with minimal TBI who
      had a scalp laceration on admission. The mean age of the patients was 30.78 +/-
      8.01 (ranging from 18 to 47) years. There were 58 (61.7%) men and 36 (38.3%)
      women among the patients. The most common finding of the Brain CT-Scan was
      subgaleal hematoma in 76 (80.9%) patients followed by base skull base fracture in
      7 (7.4%), linear skull fracture in 7 (7.4%), brain contusion in 3 (3.2%) and
      subdural hematoma in 1 (1.1%). Conclusion: The results of the current study
      indicate that scalp lacerations are associated with intracranial injuries in
      about 20% of the patients with mild TBI. Thus brain CT-scan is recommended in all
      the patients with mild TBI and scalp lacerations.

PMID- 29379811
TI  - Determinants of the Lethal Area 50 Index (LA50) in Burn Patients Admitted to a
      Tertiary Referral Burn Center in Southern Iran.
AB  - Objective: To evaluate the lethal area 50 (LA50) and determinants of mortality in
      burn patients admitted to a single burn center. Methods: This retrospective cross
      sectional study was conducted in a tertiary burn center affiliated with Shiraz
      University of Medical Sciences, Shiraz, Iran, during a 1-year period from 2015 to
      2016. To determine prognostic factors in fatal burns, medical records of eligible
      burn patients were reviewed for demographic and clinical variables, as well as
      patient outcome. Also, LA50 was calculated using Probit analysis. Results:
      Overall 559 patients with the mean age of 27.2+/-23.65 years and including 343
      (61.4%) males and 216 (38.6%) females were enrolled in this study. The average
      burn TBSA% was 31.38+/-24.41% (1-100%). Duration of hospital stay ranged from 1
      to 67 days (15.11+/-10.64). With 93 expired patients, the mortality rate was
      calculated to be 16.6%. The total LA50 was 66.55% (58.4-79.3). Fire was the most
      common cause of burn injury. Conclusion: Compared to developed countries, in our
      burn center the LA50 and survival rate of burn patients are lower. This indicates
      an urgent need for prompt attention in order to improve current policies
      regarding this public health issue to reduce mortality.

PMID- 29379812
TI  - Characteristics of the Traumatic Forensic Cases Admitted To Emergency Department
      and Errors in the Forensic Report Writing.
AB  - Objective: To identify errors in forensic reports and to describe the
      characteristics of traumatic medico-legal cases presenting to the emergency
      department (ED) at a tertiary care hospital. Methods: This study is a
      retrospective cross-sectional study. The study includes cases resulting in a
      forensic report among all traumatic patients presenting to the ED of Adiyaman
      University Training and Research Hospital, Adiyaman, Turkey during a 1-year
      period. We recorded the demographic characteristics of all the cases, time of
      presentation to the ED, traumatic characteristics of medico-legal cases, forms of
      suicide attempt, suspected poisonous substance exposure, the result of follow-up
      and the type of forensic report. Results: A total of 4300 traumatic medico-legal
      cases were included in the study and 72% of these cases were male. Traumatic
      medico-legal cases occurred at the greatest frequency in July (10.1%) and 28.9%
      of all cases occurred in summer. The most frequent causes of traumatic medico
      legal cases in the ED were traffic accidents (43.4%), violent crime (30.5%), and
      suicide attempt (7.2%). The most common method of attempted suicide was drug
      intake (86.4%). 12.3% of traumatic medico-legal cases were hospitalized and 24.2%
      of those hospitalized were admitted to the orthopedics service. The most common
      error in forensic reports was the incomplete recording of the patient's
      "cooperation" status (82.7%). Additionally, external traumatic lesions were not
      defined in 62.4% of forensic reports. Conclusion: The majority of traumatic
      medico-legal cases were male age 18-44 years, the most common source of trauma
      was traffic accidents and in the summer months. When writing a forensic report,
      emergency physicians made mistakes in noting physical examination findings and
      identifying external traumatic lesions. Physicians should make sure that the
      traumatic medico-legal patients they treat have adequate documentation for
      reference during legal proceedings. The legal duties and responsibilities of
      physicians should be emphasized with in-service training.

PMID- 29379813
TI  - Tips on Reporting a Systematic Review.

PMID- 29379814
TI  - Letter to the Editor Regarding "Tips on Reporting Systematic Reviews".

PMID- 29379815
TI  - Post-Fundoplication Dumping Syndrome: A Frequent "Rare" Complication.
AB  - Gastroparesis, caused by delayed emptying of the stomach, has been shown to be
      associated with Nissen fundoplication. However, symptomatic rapid emptying of the
      stomach is rare after Nissen fundoplication, and its treatment is often
      challenging. We report 2 patients with dumping-like syndrome post-fundoplication
      with marked improvement of symptoms after dietary management and medical
      treatment.

PMID- 29379816
TI  - Hepatopleural Fistula with Empyema Thoracis: A Rare Complication of Autosomal
      Dominant Polycystic Kidney Disease.
AB  - We report a 70-year-old man with autosomal dominant polycystic kidney disease
      (ADPKD) who presented with right-sided extended-spectrum beta-lactamases
      Escherichia coli empyema thoracis. Chest and abdominal computed tomography showed
      hepatopleural fistula. The patient refused a surgical operation and was treated
      with tube thoracotomy, percutaneous drainage of dominant liver cyst, and
      intravenous antibiotics. His symptoms improved after 2 months of nonsurgical
      treatment.

PMID- 29379817
TI  - Successful Treatment of Cannabinoid Hyperemesis Syndrome with Topical Capsaicin.
AB  - Cannabinoid hyperemesis syndrome (CHS) is a clinical entity in which marijuana
      users develop nausea, vomiting, and abdominal pain that improves with hot water
      bathing or cannabis cessation. Previous models suggest that CHS arises solely
      from the derangement of cannabinoid receptor type 1 signaling. However,
      involvement of transient receptor potential vanilloid subtype 1 (TRPV1) receptor,
      which is activated by marijuana, capsaicin, and heat, could fill gaps in existing
      models, including the enigmatic role of hot water bathing. We propose that
      chronic cannabis use decreases TRPV1 signaling and alters gastric motility, and
      we report the case of a CHS patient whose symptoms improved after topical
      capsaicin.

PMID- 29379818
TI  - MerTK-mediated regulation of myelin phagocytosis by macrophages generated from
      patients with MS.
AB  - Objective: To document functional differences between monocyte-derived
      macrophages (MDMs) of patients with MS and the ability of age/sex-matched healthy
      donor cells to phagocytose human myelin and to investigate the molecular
      mechanisms that underlie this. Methods: MDMs were derived from peripheral blood
      monocytes of 25 untreated patients with relapsing-remitting MS and secondary
      progressive MS and age/sex-matched healthy controls (HCs). Phagocytosis was
      assessed by flow cytometry using fluorescently labeled human myelin.
      Quantification of messenger RNA and protein expression of Tyro3, Axl, and MerTK
      family molecules was determined by quantitative PCR, Western blotting, and flow
      cytometry. Results: Cells of patients with MS display a reduced ability to
      phagocytose human myelin but not red blood cells as compared to matched HCs.
      These cells express significantly lower levels of the phagocytic tyrosine kinase
      receptor, MerTK, and its natural ligand, growth arrest-specific 6, independently
      of the activation state of the cells. Increased expression of interleukin 10
      following myelin uptake by healthy donor cells is lost in MDMs of patients with
      MS; this effect is mediated through the MerTK pathway. Treatment of MS cells with
      transforming growth factor beta (TGFbeta) restored both phagocytosis and
      expression deficits. Conclusions: We describe a molecular mechanism that
      underlies a defect in myelin phagocytosis by macrophages generated from patients
      with MS. This abnormality involves decreased expression of MerTK and its ligands
      and can be rescued by treatment with TGFbeta.

PMID- 29379819
TI  - Elevated EBNA-1 IgG in MS is associated with genetic MS risk variants.
AB  - Objective: To assess whether MS genetic risk polymorphisms (single nucleotide
      polymorphism [SNP]) contribute to the enhanced humoral immune response against
      Epstein-Barr virus (EBV) infection in patients with MS. Methods: Serum anti-EBV
      nuclear antigen 1 (EBNA-1) and early antigen D (EA-D) immunoglobulin gamma (IgG)
      levels were quantitatively determined in 668 genotyped patients with MS and 147
      healthy controls. Anti-varicella-zoster virus (VZV) IgG levels were used as a
      highly prevalent, non-MS-associated control herpesvirus. Associations between
      virus-specific IgG levels and MS risk SNPs were analyzed. Results: IgG levels of
      EBNA-1, but not EA-D and VZV, were increased in patients with MS compared with
      healthy controls. Increased EBNA-1 IgG levels were significantly associated with
      risk alleles of SNP rs2744148 (SOX8), rs11154801 (MYB), rs1843938 (CARD11), and
      rs7200786 (CLEC16A/CIITA) in an interaction model and a trend toward significance
      for rs3135388 (HLA-DRB1*1501). In addition, risk alleles of rs694739 (PRDX5/BAD)
      and rs11581062 (VCAM1) were independently associated and interacted with normal
      EBNA-1 IgG levels. None of these interactions were associated with EA-D and VZV
      IgG titers. Conclusions: Several MS-associated SNPs significantly correlated with
      differential IgG levels directed to a latent, but not a lytic EBV protein. The
      data suggest that the aforementioned immune-related genes orchestrate the
      aberrant EBNA-1 IgG levels.

PMID- 29379820
TI  - MS AHI1 genetic risk promotes IFNgamma+ CD4+ T cells.
AB  - Objective: To study the influence of the Abelson helper integration site 1 (AHI1)
      locus associated with MS susceptibility on CD4+ T cell function. Methods: We
      characterized the chromatin state of T cells in the MS-associated AHI1 linkage
      disequilibrium (LD) block. The expression and the role of the AHI1 variant were
      examined in T cells from genotyped healthy subjects who were recruited from the
      PhenoGenetic Project, and the function of AHI1 was explored using T cells from
      Ahi1 knockout mice. Results: Chromatin state analysis reveals that the LD block
      containing rs4896153, which is robustly associated with MS susceptibility (odds
      ratio 1.15, p = 1.65 * 10-13), overlaps with strong enhancer regions that are
      present in human naive and memory CD4+ T cells. Relative to the rs4896153A
      protective allele, the rs4896153T susceptibility allele is associated with
      decreased AHI1 mRNA expression, specifically in naive CD4+ T cells (p = 1.73 * 10
      74, n = 213), and we replicate this effect in an independent set of subjects (p =
      2.5 * 10-9, n = 32). Functional studies then showed that the rs4896153T risk
      variant and the subsequent decreased AHI1 expression were associated with reduced
      CD4+ T cell proliferation and a specific differentiation into interferon gamma
      (IFNgamma)-positive T cells when compared with the protective rs4896153A allele.
      This T cell phenotype was also observed in murine CD4+ T cells with genetic
      deletion of Ahi1. Conclusions: Our findings suggest that the effect of the AHI1
      genetic risk for MS is mediated, in part, by enhancing the development of
      proinflammatory IFNgamma+ T cells that have previously been implicated in MS and
      its mouse models.

PMID- 29379821
TI  - Multiplex family with GAD65-Abs neurologic syndromes.
AB  - Objective: Neurologic autoimmune syndromes associated with anti-glutamate acid
      decarboxylase 65 antibodies (GAD65-Abs) are rare and mostly sporadic. Methods: We
      describe a niece and her aunt with GAD65-Abs neurologic syndromes. High
      resolution HLA typing of Class I and Class II alleles was performed using next
      generation sequencing. Results: The proband had cerebellar ataxia and probable
      limbic encephalitis features, whereas her niece had stiff-person syndrome. Both
      had a high titer of GAD65-Abs in serum and CSF and showed signs of inflammation
      in CSF. Both affected members carried the same rare recombinant
      DRB1*15:01:01~DQA1*01:02:01~DQB1*05:02:01 haplotype, which may or may not be
      involved in disease susceptibility. Of interest, other unaffected members of the
      family either had the same HLA haplotype but normal serum GAD65-Abs or had
      different HLA types but a high titer of serum GAD65-Abs without neurologic
      symptoms, suggesting cumulative effects. Conclusions: This unique association
      strengthens the concept that hereditary factors, possibly including specific HLA
      haplotypes, play a role in neurologic syndromes associated with GAD65-Abs.

PMID- 29379822
TI  - ITPR1 autoimmunity: Frequency, neurologic phenotype, and cancer association.

PMID- 29379824
TI  - Palliative Care: Opportunities for Nursing.
AB  - Ayda G. Nambayan, PhD, RN is the Training Consultant for The Ruth Foundation for
      Palliative and Hospice Care. Prior to this, she held various positions as a
      Consultant for Advanced Education and Training at Makati Medical Center,
      Philippines; a curriculum and distance learning developer for www.Cure4Kids.org,
      the educational website of the International Outreach Program of St. Jude
      Children's Research Hospital in Memphis, TN. In 2002, she retired from a faculty
      position from the University of Alabama at Birmingham, where she taught Adult
      Health Nursing for 25 years. Her nursing degrees were from the University of
      Santo Tomas, Manila, Philippines, Teacher's College, Columbia University in New
      York, NY and The University of Alabama at Birmingham, Birmingham, AL. Among her
      many professional awards include the Oncology Nursing Society's Pearl Moore
      Making a Difference Award in Oncology Nursing, International Award for
      Contributions in Cancer Care and the End of Life Nursing Education Consortium
      award for Pediatric Education.

PMID- 29379823
TI  - Disease activity following pregnancy-related discontinuation of natalizumab in
      MS.
AB  - Objective: To investigate disease activity and disability progression following
      pregnancy-related discontinuation of natalizumab (NTZ) in patients with relapsing
      remitting MS. Methods: A retrospective cohort study of clinical and radiologic
      data in patients who discontinued NTZ for pregnancy-related reasons. Results:
      Twenty-two pregnancy-related NTZ discontinuations in 17 patients were evaluated.
      The median time to conception was 3.4 months. Relapses were more frequent in
      patients in whom conception did not occur within 6 months (p = 0.022). Confirmed
      disability progression occurred in 27.3% and was associated with time to
      conception (p < 0.001). Conclusions: Early conception after NTZ discontinuation
      is associated with a reduced risk of disease activity and disability progression.
      Continuation of NTZ treatment until confirmed pregnancy should be considered in
      patients with previously active MS. However, the advantages of continuing the
      drug until pregnancy should be balanced against the uncertainties in postnatal
      outcomes.

PMID- 29379825
TI  - Nursing and the Future of Palliative Care.

PMID- 29379826
TI  - Empowering Nurses through End-of-Life Nursing Education in Asia: Nurses as
      Advocates for Patients' Dignity.

PMID- 29379827
TI  - The Status of Palliative Care in the Asia-Pacific Region.

PMID- 29379828
TI  - Providing Palliative Care Education: Showcasing Efforts of Asian Nurses.
AB  - Most of the world's population lives in Asia. Prevention and detection of cancer,
      as well as ensuring equitable access to cancer care for all Asians remains a
      major public health issue and requires governmental involvement and dedicated
      resources. Palliative care, a medical and nursing specialty, promotes holistic
      attention to suffering and provides compassionate and interdisciplinary care to
      the most vulnerable in all societies-those with serious illness. It is nurses who
      provide the majority of care for patients with cancer, as no other healthcare
      professional spends more time at the bedside or out in the community assessing
      and managing these patients and their families. The purpose of this article is to
      showcase nursing leaders throughout Asia who are receiving palliative care
      education, educating their colleagues in this care, improving clinical practice,
      participating in the development of healthcare policies, and advocating for this
      care.

PMID- 29379829
TI  - Singapore Takes Six Steps Forward in 'The Quality of Death Index' Rankings.
AB  - In the latest 2015 Quality of Death Index, Singapore managed to move SIX steps
      forward from 18th to the 12th position. This advancement has been hard-won, with
      victories to improve the level of palliative care such as creating awareness of
      palliative service, improving coordinated care and growing an adequate capacity
      to meet the demand of care in our fast -growing ageing population. But it hasn't
      always been easy. Despite being a first world country, Asian societies like
      Singapore have inherited taboos regarding public dialogue about death and dying.
      Such dialogue is traditionally avoided. However, through years of continual
      effort in improving the standard of palliative care delivery, redesigning
      education module, creating public awareness and improving funding system,
      Singapore's palliative care providers have improved the lives of those with life
      limiting illnesses. Nevertheless, the government will continue to improve and
      work toward achieving single digits in the next ranking of the Quality of Death
      Index.

PMID- 29379830
TI  - Hospice and Palliative Care in China: Development and Challenges.
AB  - Hospice and palliative care have been demonstrated to improve quality of life,
      shorten hospital stays, and save costs. As a developing country, faced with a
      rapidly aging population and an increasing number of patients with life
      threatening illnesses such as cancer, China has made great progress in promoting
      hospice and palliative care during the past few decades. A trained nurse can play
      a significant role in promoting quality hospice and palliative care by providing
      care, coordinating a multidisciplinary team, calling for policy support, and
      raising public awareness. It is critical for nurses to clearly understand the
      development and challenges that currently exist in the country. With this
      awareness, nurses will improve their ability to recognize and address patients'
      and families' needs, resulting in quality, dignified, and individualized end-of
      life care.

PMID- 29379832
TI  - Cancer in the Elderly: Challenges and Barriers.

PMID- 29379831
TI  - Translating a US Early Palliative Care Model for Turkey and Singapore.
AB  - The field of palliative care is growing in acceptance and sophistication
      globally. No longer considered just for patients at end-of-life, palliative care
      is now being incorporated early in the disease trajectory. Despite professional
      guidelines supporting early palliative care, there are few models that have been
      created that can be translated into practice cross-culturally. In the United
      States, the Educate, Nurture, Advise, Before, Life Ends (ENABLE) early palliative
      care telehealth model has demonstrated effectiveness in improving quality of
      life, mood, symptom relief, and survival for patients with cancer and is now
      being tested in patients with heart failure. Family caregivers of patients who
      have received ENABLE concurrent with their care recipients have also demonstrated
      positive outcomes in quality of life and caregiver burden. Internationally, a
      number of investigators are culturally adapting ENABLE for patients and family
      caregivers. While some elements of ENABLE, such as symptom management and self
      care, and the caregiving role are relevant cross-culturally, others have been
      built on Western principles of self-determination or represent concepts such as
      advance care planning which will require more cultural adaptation. In addition,
      ENABLE was initially an in-person approach that was converted to telehealth to
      accommodate a rural population-it will be important to understand cultural norms
      related to receiving care by phone or if an in-person approach will be more
      culturally acceptable. This paper describes efforts in Turkey and Singapore to
      culturally adapt the ENABLE early palliative care principles for their countries.

PMID- 29379833
TI  - What Can Qualitative Studies Offer in a World Where Evidence Drives Decisions?
AB  - In an environment in which evidence-based practice is the espoused norm, nurses
      have understandably sought to frame the knowledge they deem relevant to practice
      decisions, including the findings of their qualitative studies, as a form of
      evidence. However, since cancer patients face a significant challenge
      interpreting various evidence claims, it is important to recognize that the
      results of our qualitative studies reflect a different form of knowledge from
      that which an evidence-based practice definition of evidence presumes. Thus, we
      need to rethink our relationship to what qualitative studies offer to the
      evidentiary dialog. An approach to qualitative inquiry that derives from a
      nursing disciplinary logic model is, therefore, presented as an alternative means
      by which to generate the kinds of knowledge nurses need to practice and to gain
      expertise in clinical wisdom. Drawing on cancer communications research as an
      example, a nursing angle of vision on how best to use qualitative approaches to
      interpret evidence and inform practice emerges.

PMID- 29379834
TI  - Breast Cancer Screening in the High-risk Population.
AB  - The risk for developing breast cancer can be influenced by a number of critical
      factors. An individual's age, gender, personal and family health history,
      nutritional status, level of physical activity, environmental exposures, and
      substance use can significantly shift the recommended screening guidelines format
      from the general risk population to a high-risk population. It is essential for
      health-care providers to become proficient in obtaining a complete cancer genetic
      risk assessment to accurately identify those who may be at high risk. There are a
      number of evidence-based risk models that can be utilized by providers to
      determine if an individual is indeed at a higher risk to develop breast cancer.
      In addition, there are evidence-based guidelines for breast cancer screening and
      possible recommendations for medical management/risk reduction that are
      appropriate to discuss for those high-risk individuals.

PMID- 29379835
TI  - How Can We Use Symptom Clusters in Nursing Care of Children with Leukemia?
AB  - The incidence of childhood cancers has been gradually rising worldwide. The rate
      of leukemia, which is the most common cancer type in childhood, has been
      increasing as well. In recent years, multiple chemotherapeutic agents,
      radiotherapy and bone marrow transplantation have been using in leukemia
      treatment. Children receiving treatment for leukemia may experience many symptoms
      due to the disease and its treatment. These concurrent symptoms may have a
      complex relationship. The aim of this paper is to review and compile current
      literature data related to symptom clusters used to explain multiple symptoms
      that occur in a complex structure due to leukemia and its treatment. Symptom
      clustering is used in oncology nursing to explain the complex relationship among
      multiple symptoms and to find out the effects that symptoms have on each other
      and patient outcomes. There are generally two statistical approaches to modeling
      symptom clusters. One is to establish the symptom clusters by grounding on
      clinical experiences, while the other is to establish them according to the
      results of statistical analysis and then clinical experiences. With the latter
      method, symptom clusters can be established more objectively and more number of
      symptoms can be assessed. In the literature, there are four instruments available
      for the measurement of a large number of symptoms in children. It is important to
      increase use of symptom clusters in nursing care for a better understanding of
      the relationship among multiple symptoms experienced during leukemia treatment, a
      more effective symptom management, and a more holistic care.

PMID- 29379836
TI  - Cost-effectiveness of Colorectal Cancer Screening and Treatment Methods: Mapping
      of Systematic Reviews.
AB  - Objective: Due to extensive literature on colorectal cancer and their
      heterogeneous results, this study aimed to summarize the systematic reviews which
      review the cost-effectiveness studies on different aspects of colorectal cancer.
      Methods: The required data were collected by searching the following key words
      according to MeSH: "colorectal cancer," "colorectal oncology," "colorectal
      carcinoma," "colorectal neoplasm," "colorectal tumors," "cost-effectiveness,"
      "systematic review," and "meta-analysis." The following databases were searched:
      PubMed, Cochrane, Google Scholar, and Scopus. Two reviewers evaluated the
      articles according to the checklist of "assessment of multiple systematic
      reviews" (AMSTAR) tool. Results: Finally, eight systematic reviews were included
      in the study. The Drummond checklist was mostly used for assessing the quality of
      the articles. The main perspective was related to the payer and the least was
      relevant to the social. The majority of the cases referred to sensitivity
      analysis (in 76% of the cases) and the lowest point also was allocated to
      discounting (in 37% of cases). The Markov model was used most widely in the
      studies. Treatment methods examined in the studies were not cost-effective in
      comparison with the studied units. Among the screening methods, computerized
      tomographic colonography and fecal DNA were cost-effective. The average score of
      the articles' qualities was high (9.8 out of 11). Conclusions: The community
      perspective should be taken into consideration at large in the studies. It is
      necessary to pay more attention to discounting subject in studies. More frequent
      application of the Markov model is recommended.

PMID- 29379837
TI  - Women's Experiences with Deciding on Neoadjuvant Systemic Therapy for Operable
      Breast Cancer: A Qualitative Study.
AB  - Objective: We explored, qualitatively, in a sample of Australian early-stage
      breast cancer patients eligible for neoadjuvant systemic therapy (NAST): (i)
      their understanding of the choice of having NAST; (ii) when and with whom the
      decision on NAST was made; and (iii) strategies used by patients to facilitate
      their decision on NAST. Methods: A sub-sample of patients participating in a
      larger intervention trial took part in this study. A total of 24 semi-structured
      phone interviews were analyzed using framework analysis. Results: A number of
      women perceived they were not offered a treatment choice. Most patients reported
      that the decision on NAST was made during or shortly after the initial
      consultation with their doctor. Women facilitated decision-making by reducing
      deciding factors and "claiming" the decision. Most women reported that they made
      the final decision, although they did not feel actively involved in the decision
      making process. Conclusions: When deciding on NAST, patient-centered care is not
      always delivered to patients. Clinicians should emphasize to patients that they
      have a treatment choice, explain the preference-sensitive nature of deciding on
      NAST and highlight that patients should be involved in this treatment decision.
      Providing patients with appropriate time and tailored take-home information might
      facilitate patient decision-making. Process-orientated research is needed to
      adequately examine patient involvement in complex treatment decisions.

PMID- 29379838
TI  - Palliative Chemotherapy: The Perspectives and Experiences of South African
      Nurses.
AB  - Objective: The objective of this study was to describe the perspectives and
      experiences of South African nurses caring for patients receiving palliative
      chemotherapy. Methods: A qualitative descriptive design was used and purposive
      sampling allowed us to select 11 nurses practising in a private ambulatory cancer
      care center in Port Elizabeth. In-depth interviews, guided by three broad themes
      were conducted and analyzed using qualitative content analyses. Data saturation
      determined the sample size. Results: Two themes emerged from the data - the
      patients cling to hope and the positive influence of palliative chemotherapy. The
      participants believed that patients consenting to palliative chemotherapy were
      clinging to false hope. They were also of the opinion that family members
      pressurize patients to consent to treatment. The participants experienced
      palliative chemotherapy positively, especially when an improvement in the
      patients' quality of life or pain relief was evident. Fatigue was highlighted as
      the major side effect, but it did not temper the participants' positive attitudes
      toward the treatment. Conclusions: Although the participants believed that
      patients cling to hope and consent to palliative chemotherapy because they hope
      to be cured, they experienced the treatment as positive. For them, the
      improvement in pain and quality of life outweighed the side effects the patients
      experienced. The positive attitude patients upheld while receiving this treatment
      encouraged them. Nurses should gain more knowledge about the meaning, people
      living with advanced cancer, attach to hope to prevent them from interpreting
      patients' hope as denial and false.

PMID- 29379839
TI  - Psychological Flexibility of Nurses in a Cancer Hospital: Preliminary Validation
      of a Chinese Version of the Work-related Acceptance and Action Questionnaire.
AB  - Objective: To translate the English work-related acceptance and action
      questionnaire (WAAQ), make cross-cultural adaptations, and examine its
      psychometric properties when used by Chinese oncology nurses. Methods: After
      translation, the psychometric properties of the Chinese WAAQ were analyzed among
      417 nurses, and content validity was determined by six experts. Results: Item
      level content validity index (CVI) values were between 0.83 and 1.00; scale-level
      CVI/universal agreement (S-CVI/UA) and S-CVI/average were 0.86 and 0.98,
      respectively, which implicated a good content validity. The correlation of the
      Chinese WAAQ with AAQ-II (rs = -0.247, P < 0.001) suggested criterion validity,
      and those with General Health Questionnaire-12 (-0.250, <0.001) and general self
      efficacy scale (0.491, <0.001) and Utrecht work engagement scale (UWES) (0.439,
      <0.001) suggested convergent validity. Exploratory factor analysis identified a
      seven-item, one-factor structure of WAAQ. The Chinese version of WAAQ had high
      internal consistency (Cronbach's alpha = 0.920), with an item-total correlation
      coefficient of 0.702-0.828 (P < 0.05), split-half reliability of 0.933, and test
      retest reliability of 0.772. Conclusions: The Chinese WAAQ is a reliable and
      valid tool for assessing psychological flexibility in Chinese oncology nurses.

PMID- 29379840
TI  - Survey of Difficult Experiences of Nurses Caring for Patients Undergoing
      Radiation Therapy: An Analysis of Factors in Difficult Cases.
AB  - Objective: The purpose of this study was to analyze the difficult experiences of
      nurses who cared for patients undergoing radiation therapy and factors related to
      patient feelings toward the progress and difficulties of treatment and the kind
      of care needed. Methods: A descriptive survey using a questionnaire. Anonymous
      self-report data were collected from a sample of 228 nurses who had 2-5 years of
      nursing experience in a National University Hospital in Japan. Years of working
      experience; knowledge and training in radiation therapy and difficult experiences
      of nurses caring for patients undergoing radiation therapy. Results: In hospital
      "A", about 80% of the nurses had cared for patients undergoing radiation therapy,
      and about 40% had experience with difficult cases. The characteristics of
      competent nurses in radiation nursing were the following: while not having
      knowledge and experience, they were seriously facing their patients. However, the
      treatment process could not be predicted, skills related to the whole-human
      involvement of patients were insufficient, and communication was similar. In
      addition, the characteristics of competent nurses in radiation nursing became
      apparent. Although these nurses lacked knowledge and experience, they interacted
      with patients in a serious manner. However, the treatment process could not be
      predicted, and the skills related to the holistic involvement of patients were
      insufficient. Furthermore, communication between the nurses and patients was
      difficult. Conclusions: Competent nurses with 2-5 years of working experience,
      but lacking specific knowledge and experience regarding radiation therapy could
      cope with difficult radiation therapy cases. However, additional education,
      training, and mentoring from expert nurses would improve the quality of care for
      patients undergoing radiation therapy and reduce distress for nurses with less
      experience. In this study, the need for educational measures and a support system
      to help competent nurses face difficult cases were suggested.

PMID- 29379841
TI  - Nursing Students' Perspectives on Assisting Cancer Patients.
AB  - Objective: The objective of this study was to examine the experiences of student
      nurses who have provided care to cancer patients. Methods: A mixed method
      approach consisting of semistructured focus groups (n = 61) and a survey
      questionnaire (n = 129) was used in the study. Student nurses were first
      interviewed, and then, a questionnaire was developed for them to answer.
      Following the content analysis, three themes and 19 subthemes were identified.
      Frequency and percent were used for qualitative data. Results: Among the student
      nurses, 80.6% reported that working with cancer patients was "difficult."
      Difficulties experienced by the student nurses included patients rejecting their
      care, a large number of problems cases encountered when providing care to cancer
      patients, communication problems (38.0%), working with patients and attendants
      who fear death, and problems arising from family attendants who obstruct care.
      The majority of students experienced patients fearing death (28.7%) and felt
      feelings such as pity (71.1%), sadness (50.0%), and fear of cancer (41.9%) during
      their internships in oncology clinics. Conclusions: Students should be supported
      by instructors and oncology nurses, and nursing curricula should contain topics
      on how to best approach cancer patients.

PMID- 29379842
TI  - A Comparative Study of Hypofractionated and Conventional Radiotherapy in
      Postmastectomy Breast Cancer Patients.
AB  - Objective: The aim of this study was to compare toxicity and locoregional control
      of short duration hypofractionated (HF) radiotherapy (RT) with conventional RT in
      breast cancer patients. Methods: A total of 100 postmastectomy breast cancer
      patients were randomized for adjuvant RT in control group (comprising fifty
      patients who received the standard conventional dose of 50 Gy in 25 fractions
      with 2 Gy per fraction) and study group (comprising fifty patients who received
      HF RT with dose of 42.72 Gy in 16 fractions with 2.67 Gy per fraction). All
      patients were treated on linear accelerator with 3-dimensional conformal RT
      technique. Outcome was analyzed in terms of toxicity, tolerability, and
      locoregional control. Results: In the present study, at a median follow-up of 20
      months, almost similar results were seen in both the groups in terms of toxicity,
      tolerability, and locoregional control. Adjuvant postmastectomy HF RT was found
      to be well tolerated with mild-to-moderate side effects that neither reached
      statistical significance nor warranted any treatment
      interruption/hospitalization. Conclusions: HF postmastectomy RT is comparable to
      conventional RT without evidence of higher adverse effects or inferior
      locoregional tumor control and has an added advantage of increased compliance
      because of short duration; hence, it can help in accommodating more breast cancer
      patients in a calendar year, ultimately resulting in decreased waiting list,
      increased turnover, and reduced cost of treatment.

PMID- 29379843
TI  - Effect of Education Based on Health Belief Model on the Behavior of Breast Cancer
      Screening in Women.
AB  - Objective: The purpose of this study was to determine the effect of education
      based on health belief model (HBM) on the behavior of breast cancer screening
      (bCS) in women. Methods: This quasi-experimental study was conducted on 226 women
      who were selected with cluster sampling method from those referred to Dezful
      health centers. Data collection tool was a researcher-made questionnaire.
      Demographic questionnaire bCS- scale, and the Knowledge about questionnaire, all
      given before and 3 months after the intervention. Results: According to the
      findings of the study, there was a significant relationship between women's
      performance and variables of knowledge, perceived sensitivity, perceived
      benefits, perceived barriers, self-efficacy, and cues to action. Conclusions:
      Poor knowledge of women indicates a crucial need for formal educational programs
      to sensitize women regarding the importance of bCS. These educational programs
      should consider factors affecting bCS behaviors.

PMID- 29379844
TI  - Developing Written Information for Cancer Survivors from Culturally and
      Linguistically Diverse Backgrounds: Lessons Learnt.
AB  - Australia is a multicultural nation with a large migrant population. Migrants
      with cancer report inferior quality of life and the need for more information in
      their own language. This paper describes lessons learnt from developing
      culturally appropriate written information resources with and for Arabic,
      Italian, and Vietnamese cancer survivors and carers. The information needs of
      survivors from these language groups as well as guidelines for the development of
      written resources for culturally diverse populations were identified through
      literature review. Community consultation was undertaken with focus groups. The
      content was developed and tested with health professionals who spoke the
      appropriate language and focus group participants, ensuring relevance and
      appropriateness. Resource design and dissemination were informed through
      community consultation. A number of key tasks for developing resources were
      identified as follows: (1) community engagement and consultation; (2) culturally
      sensitive data collection; (3) focus group facilitators (recruitment and
      training); (4) content development; (5) translation and review process; (6)
      design; and (7) sustainability. This project reinforced literature review
      findings on the importance of cultural sensitivity in the development of
      resources. Engaging with community groups and incorporating culturally
      appropriate recruitment strategies optimises recruitment to focus groups and
      facilitates content development. Stakeholders and lay persons from the intended
      ethnic-minority communities should be involved in the development and formative
      evaluation of resources to ensure appropriateness and relevance and in the
      dissemination strategy to optimize penetration. We believe the lessons we have
      learnt will be relevant to any group intending to develop health information for
      culturally and linguistic diverse groups.

PMID- 29379846
TI  - Erratum: Telomeres and Stress: Promising Avenues for Research in Psycho-Oncology.
AB  - [This corrects the article on p. 137 in vol. 3, PMID: 27981152.].

PMID- 29379845
TI  - Navigate the World with College of Nursing, Taipei Medical University, Ranked No.
      1 Nationally in Nursing Subject, Academic Ranking of World Universities (ARWU).

PMID- 29379847
TI  - Aberrant tryptophan transport in cultured fibroblast from patients with Male
      Idiopathic Osteoporosis: An in vitro study.
AB  - It has been demonstrated, that long-term chronic tryptophan deficiency, results
      in decreased serotonin synthesis, which may lead to low bone mass and low bone
      formation. Findings from studies in male patients with idiopathic osteoporosis
      suggested a decreased transport of tryptophan in erythrocytes of osteoporotic
      patients, indicating that serotonin system defects may be involved in the
      etiology of low bone mass. Tryptophan is the precursor of serotonin, and a
      disturbed transport of tryptophan is implicated in altered serotonin synthesis.
      However, no study has investigated the tryptophan transport kinetics in MIO
      patients. The aim of this study is to investigate the kinetic parameters of
      tryptophan transport in fibroblasts derived from MIO patients compared to age and
      sex matched controls. Fibroblast cells were cultured from skin biopsies obtained
      from 14 patients diagnosed with Male Idiopathic Osteoporosis and from 13 healthy
      age-sex matched controls, without a diagnosis of osteoporosis. Transport of the
      amino acid tryptophan across the cell membrane was measured by the cluster tray
      method. The kinetic parameters, maximal transport capacity (Vmax) and affinity
      constant (Km) were determined by using the Lineweaver-Burke plot equation. The
      results of this study have shown a significantly lower mean value for Vmax (p =
      0.0138) and lower Km mean value (p = 0.0009) of tryptophan transport in
      fibroblasts of MIO patients compared to the control group. A lower Vmax implied a
      decreased tryptophan transport availability in MIO patients. In conclusion,
      reduced cellular tryptophan availability in MIO patients might result in reduced
      brain serotonin synthesis and its endogenous levels in peripheral tissues, and
      this may contribute to low bone mass/formation. The findings of the present study
      could contribute to the etiology of idiopathic osteoporosis and for the
      development of novel approaches for diagnosis, treatment and management
      strategies of MIO.

PMID- 29379849
TI  - Heart rate and sentiment experimental data with common timeline.
AB  - Sentiment extraction and analysis using spoken utterances or written corpora as
      well as collection and analysis of human heart rate data using sensors are
      commonly used techniques and methods. On the other hand, these have been not
      combined yet. The collected data can be used e.g. to investigate the mutual
      dependence of human physical and emotional activity. The paper describes the
      procedure of parallel acquisition of heart rate sensor data and tweets expressing
      sentiment and difficulties related to this procedure. The obtained datasets are
      described in detail and further discussed to provide as much information as
      possible for subsequent analyses and conclusions. Analyses and conclusions are
      not included in this paper. The presented experiment and provided datasets serve
      as the first basis for further studies where all four presented data sources can
      be used independently, combined in a reasonable way or used all together. For
      instance, when the data is used all together, performing studies comparing human
      sensor data, acquired noninvasively from the surface of the human body and
      considered as more objective, and human written data expressing the sentiment,
      which is at least partly cognitively interpreted and thus considered as more
      subjective, could be beneficial.

PMID- 29379848
TI  - Bone adaptation in response to treadmill exercise in young and adult mice.
AB  - Exercise is a key determinate of fracture risk and provides a clinical means to
      promote bone formation. However, the efficacy of exercise to increase bone mass
      declines with age. The purpose of this study was to identify age-related
      differences in the anabolic response to exercise at the cellular and tissue
      level. To this end, young (8-weeks of age) and adult (36-weeks of age) male mice
      were subjected to a moderate exercise regimen of running on a treadmill. As a
      result, exercise had a significant effect on PTHrP and SOST gene expression
      during the first week that was dependent upon age. In particular, young mice
      displayed an increase in PTHrP expression and decrease in SOST expression, both
      of which remained unaffected by exercise in the adult mice. After 5-weeks of
      exercise, a significant decrease in the percentage of osteocytes expressing
      sclerostin at the protein level was found in young mice, but not adult mice.
      Mechanical testing of the tibia found exercise to have a significant influence on
      tissue-level mechanical properties, specifically ultimate-stress and modulus that
      was dependent on age. Adult mice in particular experienced a significant decrease
      in modulus despite an increase in cortical area and cortical thickness compared
      to sedentary controls. Altogether, this study demonstrates a shift in the
      cellular response to exercise with age, and that gains in bone mass at the adult
      stage fail to improve bone strength.

PMID- 29379850
TI  - Online survey data of public subjective well-being on high occupancy vehicle lane
      in China.
AB  - The data presented in this article are related to the research article entitled
      "Out-of-home activities, daily travel, and SWB" (Ettema et al., 2010) [1]. The
      paper provides an online survey questionnaire and data about the public
      subjective well-being of high occupancy vehicle lanes in China. The survey data
      are made publicly available to extended analysis.

PMID- 29379851
TI  - Biochemical data from the characterization of a new pathogenic mutation of human
      pyridoxine-5'-phosphate oxidase (PNPO).
AB  - PNPO deficiency is responsible of severe neonatal encephalopathy, responsive to
      pyridoxal-5'-phosphate (PLP) or pyridoxine. Recent studies widened the phenotype
      of this condition and detected new genetic variants on PNPO gene, whose
      pathogenetic role and clinical expression remain to be established. One of these
      mutations, Arg116Gln, is of particular interest because of its later onset of
      symptoms (beyond the first months of life) and its peculiar epileptic
      manifestations in patients. This protein variant was expressed as recombinant
      protein in E coli, purified to homogeneity, and characterized with respect to
      structural and kinetic properties, stability, binding constants of cofactor
      flavin mononucleotide (FMN) and product (PLP) in order to define the molecular
      and structural bases of its pathogenicity. For interpretation and discussion of
      reported data, together with the description of clinical studies, refer to the
      article [1] (doi: 10.1016/j.ymgme.2017.08.003).

PMID- 29379852
TI  - Dataset on gait patterns in degenerative neurological diseases.
AB  - We collected the gait parameters and lower limb joint kinematics of patients with
      three different types of primary degenerative neurological diseases: (i)
      cerebellar ataxia (19 patients), (ii) hereditary spastic paraparesis (26
      patients), and (iii) Parkinson's disease (32 patients). Sixty-five gender-age
      matched healthy subjects were enrolled as control group. An optoelectronic motion
      analysis system was used to measure time-distance parameters and lower limb joint
      kinematics during gait in both patients and healthy controls.

PMID- 29379853
TI  - Data on evolutionary relationships between hearing reduction with history of
      disease and injuries among workers in Abadan Petroleum Refinery, Iran.
AB  - The present work examined data obtained during the analysis of Hearing Reduction
      (HR) of Abadan Petroleum Refinery (Abadan PR) workers of Iran with a history of
      disease and injuries. To this end, all workers in the refinery were chosen. In
      this research, the effects of history of disease and injury including trauma,
      electric shock, meningitis-typhoid disease and genetic illness as well as contact
      with lead, mercury, CO2 and alcohol consumption were evaluated (Lie, et al.,
      2016) [1]. After the completion of the questionnaires by workers, the coded data
      were fed into EXCELL. Statistical analysis of data was carried out, using SPSS
      16.

PMID- 29379854
TI  - The effect of education on the nursing care quality of patients who are under
      mechanical ventilation in ICU ward.
AB  - Nurses have the most important role among health care workers (HCWs) in each
      hospital (Aiken et al., 2008) [1]. Nurses education can lead to the improvement
      of nursing care If is implemented and designed based on nurses' needs and proper
      principles (Aiken et al., 2008) [1]. Nowadays, increased quality of the treatment
      and increase the chances of survival of patients with acute respiratory failure
      are very important (Teixeira et al., 2013) [2]. Nursing care plan in ICU patients
      is one of the important elements in nursing care, and one of the main strategies
      is promotion of education level. Nurses due to longtime relationship with nursing
      staff in 24 hours and use of multiple roles of education have excellent position
      in evaluating educational needs and performing clinical educator roles. The
      effect of education on the nursing care quality of patients who were under
      mechanical ventilation (UMV) in intensive care unit (ICU) ward of Razi hospital
      is evaluated during 2015. The present study is descriptive-analytical and semi
      experimental research. Research statistical population included 30 nurses. In
      this paper, the effects of communication with the patient, correct suctioning,
      compliance of aseptic techniques, the correct discharge of tube cuff, chest
      physiotherapy, the correct change positions, health food gavage, prevent of foot
      drop, oral hygiene, the eyes hygiene and protect the cornea have been studied.
      After completion of the questionnaires by patients, the obtained coded data were
      fed into EXCEL. Reliability was confirmed with coefficient Alfa 0.86 and the
      result of software and techniques were entered to SPSS for statistics and
      analysis.

PMID- 29379857
TI  - Chronic granulomatous reaction in patients receiving vaccine immunotherapy for
      metastatic melanoma.

PMID- 29379855
TI  - A Cell Culture Platform to Maintain Long-term Phenotype of Primary Human
      Hepatocytes and Endothelial Cells.
AB  - Background and Aims: Modeling interactions between primary human hepatocytes
      (PHHs) and primary human liver sinusoidal endothelial cells (LSECs) in vitro can
      help elucidate human-specific mechanisms underlying liver physiology/disease and
      drug responses; however, existing hepatocyte/endothelial coculture models are
      suboptimal because of their use of rodent cells, cancerous cell lines, and/or
      nonliver endothelial cells. Hence, we sought to develop a platform that could
      maintain the long-term phenotype of PHHs and primary human LSECs. Methods:
      Primary human LSECs or human umbilical vein endothelial cells as the nonliver
      control were cocultivated with micropatterned PHH colonies (to control homotypic
      interactions) followed by an assessment of PHH morphology and functions (albumin
      and urea secretion, and cytochrome P-450 2A6 and 3A4 enzyme activities) over 3
      weeks. Endothelial phenotype was assessed via gene expression patterns and
      scanning electron microscopy to visualize fenestrations. Hepatic responses in
      PHH/endothelial cocultures were benchmarked against responses in previously
      developed PHH/3T3-J2 fibroblast cocultures. Finally, PHH/fibroblast/endothelial
      cell tricultures were created and characterized as described previously. Results:
      LSECs, but not human umbilical vein endothelial cells, induced PHH albumin
      secretion for ~11 days; however, neither endothelial cell type could maintain PHH
      morphology and functions to the same magnitude/longevity as the fibroblasts. In
      contrast, both PHHs and endothelial cells displayed stable phenotype for 3 weeks
      in PHH/fibroblast/endothelial cell tricultures; furthermore, layered tricultures
      in which PHHs and endothelial cells were separated by a protein gel to mimic the
      space of Disse displayed similar functional levels as the coplanar tricultures.
      Conclusions: PHH/fibroblast/endothelial tricultures constitute a robust platform
      to elucidate reciprocal interactions between PHHs and endothelial cells in
      physiology, disease, and after drug exposure.

PMID- 29379858
TI  - Dementia, diarrhea, desquamating shellac-like dermatitis revealing late-onset
      cobalamin C deficiency.

PMID- 29379856
TI  - Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower
      Esophageal Sphincter Via Na+/Ca2+ Exchanger.
AB  - Background and Aims: Hydrogen sulfide (H2S) is a major physiologic
      gastrotransmitter. Its role in the regulation of the lower esophageal sphincter
      (LES) function remains unknown. The present study addresses this question.
      Methods: Isometric contraction was monitored in circular smooth muscle strips of
      porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were
      simultaneously monitored in fura-2-loaded strips with front-surface fluorometry.
      The contribution of endogenous H2S to LES contractility was investigated by
      examining the effects of inhibitors of H2S-generating enzymes, including
      cystathionine-beta-synthase, cystathionine-gamma-lyase, and 3-mercaptopyruvate
      sulfurtransferase, on the LES function. Results: Porcine LES strips myogenically
      maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine
      beta-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate
      sulfurtransferase inhibitor) but not DL-PAG (cystathionine-gamma-lyase
      inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were
      additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L
      Asp. Immunohistochemical analyses revealed that cystathionine-beta-synthase and 3
      mercaptopyruvate sulfurtransferase, but not cystathionine-gamma-lyase, were
      expressed in porcine LES. AOA+L-Asp-induced relaxation was accompanied by a
      decrease in [Ca2+]i and inversely correlated with the extracellular Na+
      concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+
      exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly
      augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic
      mice compared with wild-type mice. Conclusions: Endogenous H2S regulates the LES
      myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S
      generating enzymes may be a potential therapeutic target for esophageal motility
      disorders, such as achalasia.

PMID- 29379859
TI  - Cutaneous Langerhans cell histiocytosis with gastrointestinal involvement treated
      with dabrafenib.

PMID- 29379860
TI  - Suppression of pathergy in pyoderma gangrenosum with infliximab allowing for
      successful tendon debridement.

PMID- 29379861
TI  - Exposed hardware in a patient with invasive keratinocyte carcinoma.

PMID- 29379862
TI  - Removal of forearm lentigines in dyschromatosis universalis hereditaria with a
      755-nm Q-switched alexandrite laser.

PMID- 29379863
TI  - Herpes zoster infection after topical steroid use in the setting of tumid lupus
      erythematosus.

PMID- 29379864
TI  - Guide to enable health charities to increase recruitment to clinical trials on
      dementia.
AB  - Introduction: The Alzheimer Society embarked on a project to improve ways that
      the 60 provincial and local Societies in Canada can work with local researchers
      to support recruitment of volunteers to clinical trials and studies. A Guide to
      assist these offices was produced to design ethical recruitment of research
      volunteers within their client populations. Methods: Consultations with
      individuals from provincial and local Societies, as well as researchers and
      leaders from health-related organizations, were conducted to identify in what
      ways these organizations are involved in study volunteer recruitment, what is and
      is not working, and what would be helpful to support future efforts. The Guide
      prototype used scenarios to illustrate study volunteer recruitment practices as
      they have been or could be applied in Societies. An implementable version of the
      Guide was produced with input from multiple internal and external reviewers
      including subject-matter experts and target users from Societies. Results:
      Society staff reported that benefits of using the Guide were that it served as a
      catalyst for conversation and reflection and identified the need for a policy.
      Also, it enabled Society readiness to respond to requests by persons with
      dementia and their caregivers wishing to participate in research. A majority
      (94%) of participating Society staff across Canada agreed that they would
      increase their capacity to support research recruitment. Discussion: Charitable
      organizations that raise funds for research have a role in promoting the
      recruitment of persons with dementia and their caregivers into clinical trials
      and studies. The Guide was produced to facilitate organizational change to both
      create a positive culture regarding research as well as practical solutions that
      can help organizations achieve this goal.

PMID- 29379865
TI  - Transcranial Alternating Current Stimulation Modulates Risky Decision Making in a
      Frequency-Controlled Experiment.
AB  - In this study, we investigated the effect of transcranial alternating current
      stimulation (tACS) on voluntary risky decision making and executive control in
      humans. Stimulation was delivered online at 5 Hz (theta), 10 Hz (alpha), 20 Hz
      (beta), and 40 Hz (gamma) on the left and right frontal area while participants
      performed a modified risky decision-making task. This task allowed participants
      to voluntarily select between risky and certain decisions associated with
      potential gains or losses, while simultaneously measuring the cognitive control
      component (voluntary switching) of decision making. The purpose of this
      experimental design was to test whether voluntary risky decision making and
      executive control can be modulated with tACS in a frequency-specific manner. Our
      results revealed a robust effect of a 20-Hz stimulation over the left prefrontal
      area that significantly increased voluntary risky decision making, which may
      suggest a possible link between risky decision making and reward processing,
      underlined by beta-oscillatory activity.

PMID- 29379866
TI  - Combination of Interaural Level and Time Difference in Azimuthal Sound
      Localization in Owls.
AB  - A function of the auditory system is to accurately determine the location of a
      sound source. The main cues for sound location are interaural time (ITD) and
      level (ILD) differences. Humans use both ITD and ILD to determine the azimuth.
      Thus far, the conception of sound localization in barn owls was that their facial
      ruff and asymmetrical ears generate a two-dimensional grid of ITD for azimuth and
      ILD for elevation. We show that barn owls also use ILD for azimuthal sound
      localization when ITDs are ambiguous. For high-frequency narrowband sounds,
      midbrain neurons can signal multiple locations, leading to the perception of an
      auditory illusion called a phantom source. Owls respond to such an illusory
      percept by orienting toward it instead of the true source. Acoustical
      measurements close to the eardrum reveal a small ILD component that changes with
      azimuth, suggesting that ITD and ILD information could be combined to eliminate
      the illusion. Our behavioral data confirm that perception was robust against
      ambiguities if ITD and ILD information was combined. Electrophysiological
      recordings of ILD sensitivity in the owl's midbrain support the behavioral
      findings indicating that rival brain hemispheres drive the decision to orient to
      either true or phantom sources. Thus, the basis for disambiguation, and reliable
      detection of sound source azimuth, relies on similar cues across species as
      similar response to combinations of ILD and narrowband ITD has been observed in
      humans.

PMID- 29379867
TI  - Electrophysiology Reveals the Neural Dynamics of Naturalistic Auditory Language
      Processing: Event-Related Potentials Reflect Continuous Model Updates.
AB  - The recent trend away from ANOVA-based analyses places experimental
      investigations into the neurobiology of cognition in more naturalistic and
      ecologically valid designs within reach. Using mixed-effects models for epoch
      based regression, we demonstrate the feasibility of examining event-related
      potentials (ERPs), and in particular the N400, to study the neural dynamics of
      human auditory language processing in a naturalistic setting. Despite the large
      variability between trials during naturalistic stimulation, we replicated
      previous findings from the literature: the effects of frequency, animacy, and
      word order and find previously unexplored interaction effects. This suggests a
      new perspective on ERPs, namely, as a continuous modulation reflecting continuous
      stimulation instead of a series of discrete and essentially sequential processes
      locked to discrete events.

PMID- 29379869
TI  - Layer-specific Developmental Changes in Excitation and Inhibition in Rat Primary
      Visual Cortex.
AB  - Cortical circuits are profoundly shaped by experience during postnatal
      development. The consequences of altered vision during the critical period for
      ocular dominance plasticity have been extensively studied in rodent primary
      visual cortex (V1). However, little is known about how eye opening, a naturally
      occurring event, influences the maturation of cortical microcircuits. Here we
      used a combination of slice electrophysiology and immunohistochemistry in rat V1
      to ask whether manipulating the time of eye opening for 3 or 7 d affects cortical
      excitatory and inhibitory synaptic transmission onto excitatory neurons uniformly
      across layers or induces laminar-specific effects. We report that binocular
      delayed eye opening for 3 d showed similar reductions of excitatory and
      inhibitory synaptic transmission in layers 2/3, 4, and 5. Synaptic transmission
      recovered to age-matched control levels if the delay was prolonged to 7 d,
      suggesting that these changes were dependent on binocular delay duration.
      Conversely, laminar-specific and long-lasting effects were observed if eye
      opening was delayed unilaterally. Our data indicate that pyramidal neurons
      located in different cortical laminae have distinct sensitivity to altered
      sensory drive; our data also strongly suggest that experience plays a fundamental
      role in not only the maturation of synaptic transmission, but also its
      coordination across cortical layers.

PMID- 29379868
TI  - Cortical Afferents and Myeloarchitecture Distinguish the Medial Intraparietal
      Area (MIP) from Neighboring Subdivisions of the Macaque Cortex.
AB  - The parietal reach region (PRR) in the medial bank of the macaque intraparietal
      sulcus has been a subject of considerable interest in research aimed at the
      development of brain-controlled prosthetic arms, but its anatomical organization
      remains poorly characterized. We examined the anatomical organization of the
      putative PRR territory based on myeloarchitecture and retrograde tracer
      injections. We found that the medial bank includes three areas: an extension of
      the dorsal subdivision of V6A (V6Ad), the medial intraparietal area (MIP), and a
      subdivision of area PE (PEip). Analysis of corticocortical connections revealed
      that both V6Ad and MIP receive inputs from visual area V6; the ventral
      subdivision of V6A (V6Av); medial (PGm, 31), superior (PEc), and inferior
      (PFG/PF) parietal association areas; and intraparietal areas AIP and VIP. They
      also receive long-range projections from the superior temporal sulcus (MST, TPO),
      cingulate area 23, and the dorsocaudal (area F2) and ventral (areas F4/F5)
      premotor areas. In comparison with V6Ad, MIP receives denser input from
      somatosensory areas, the primary motor cortex, and the medial motor fields, as
      well as from visual cortex in the ventral precuneate cortex and frontal regions
      associated with oculomotor guidance. Unlike MIP, V6Ad receives stronger visual
      input, from the caudal inferior parietal cortex (PG/Opt) and V6Av, whereas PEip
      shows marked emphasis on anterior parietal, primary motor, and ventral premotor
      connections. These anatomical results suggest that MIP and V6A have complementary
      roles in sensorimotor behavior, with MIP more directly involved in movement
      planning and execution in comparison with V6A.

PMID- 29379870
TI  - Topoisomerase IIbeta Selectively Regulates Motor Neuron Identity and Peripheral
      Connectivity through Hox/Pbx-Dependent Transcriptional Programs.
AB  - Vital motor functions, such as respiration and locomotion, rely on the ability of
      spinal motor neurons (MNs) to acquire stereotypical positions in the ventral
      spinal cord and to project with high precision to their peripheral targets. These
      key properties of MNs emerge during development through transcriptional programs
      that dictate their subtype identity and connectivity; however, the molecular
      mechanisms that establish the transcriptional landscape necessary for MN
      specification are not fully understood. Here, we show that the enzyme
      topoisomerase IIbeta (Top2beta) controls MN migration and connectivity.
      Surprisingly, Top2beta is not required for MN generation or survival but has a
      selective role in columnar specification. In the absence of Top2beta, phrenic MN
      identity is eroded, while other motor columns are partially preserved but fail to
      cluster to their proper position. In Top2beta-/- mice, peripheral connectivity is
      impaired as MNs exhibit a profound deficit in terminal branching. These defects
      likely result from the insufficient activation of Hox/Pbx-dependent
      transcriptional programs as Hox and Pbx genes are downregulated in the absence of
      Top2beta. Top2beta mutants recapitulate many aspects of Pbx mutant mice, such as
      MN disorganization and defects in medial motor column (MMC) specification. Our
      findings indicate that Top2beta, a gene implicated in neurodevelopmental diseases
      such as autism spectrum disorders, plays a critical, cell-specific role in the
      assembly of motor circuits.

PMID- 29379871
TI  - Closed-Loop Estimation of Retinal Network Sensitivity by Local Empirical
      Linearization.
AB  - Understanding how sensory systems process information depends crucially on
      identifying which features of the stimulus drive the response of sensory neurons,
      and which ones leave their response invariant. This task is made difficult by the
      many nonlinearities that shape sensory processing. Here, we present a novel
      perturbative approach to understand information processing by sensory neurons,
      where we linearize their collective response locally in stimulus space. We added
      small perturbations to reference stimuli and tested if they triggered visible
      changes in the responses, adapting their amplitude according to the previous
      responses with closed-loop experiments. We developed a local linear model that
      accurately predicts the sensitivity of the neural responses to these
      perturbations. Applying this approach to the rat retina, we estimated the optimal
      performance of a neural decoder and showed that the nonlinear sensitivity of the
      retina is consistent with an efficient encoding of stimulus information. Our
      approach can be used to characterize experimentally the sensitivity of neural
      systems to external stimuli locally, quantify experimentally the capacity of
      neural networks to encode sensory information, and relate their activity to
      behavior.

PMID- 29379872
TI  - Altered Chloride Homeostasis Decreases the Action Potential Threshold and
      Increases Hyperexcitability in Hippocampal Neurons.
AB  - Chloride ions play an important role in controlling excitability of principal
      neurons in the central nervous system. When neurotransmitter GABA is released
      from inhibitory interneurons, activated GABA type A (GABAA) receptors on
      principal neurons become permeable to chloride. Typically, chloride flows through
      activated GABAA receptors into the neurons causing hyperpolarization or shunting
      inhibition, and in turn inhibits action potential (AP) generation. However, in
      situations when intracellular chloride concentration is increased, chloride ions
      can flow in opposite direction, depolarize neurons, and promote AP generation. It
      is generally recognized that altered chloride homeostasis per se has no effect on
      the AP threshold. Here, we demonstrate that chloride overload of mouse principal
      CA3 pyramidal neurons not only makes these cells more excitable through GABAA
      receptor activation but also lowers the AP threshold, further aggravating
      excitability. This phenomenon has not been described in principal neurons and
      adds to our understanding of mechanisms regulating neuronal and network
      excitability, particularly in developing brain and during pathological situations
      with altered chloride homeostasis. This finding further broadens the spectrum of
      neuronal plasticity regulated by ionic compositions across the cellular membrane.

PMID- 29379873
TI  - A Common Function of Basal Ganglia-Cortical Circuits Subserving Speed in Both
      Motor and Cognitive Domains.
AB  - Distinct regions of the frontal cortex connect with their basal ganglia and
      thalamic counterparts, constituting largely segregated basal ganglia-thalamo
      cortical (BTC) circuits. However, any common role of the BTC circuits in
      different behavioral domains remains unclear. Indeed, whether dysfunctional motor
      and cognitive BTC circuits are responsible for motor slowing and cognitive
      slowing, respectively, in Parkinson's disease (PD) is a matter of debate. Here,
      we used an effortful behavioral paradigm in which the effects of task rate on
      accuracy were tested in movement, imagery, and calculation tasks in humans. Using
      nonlinear fitting, we separated baseline accuracy (Abase ) and "agility" (ability
      to function quickly) components of performance in healthy participants and then
      confirmed reduced agility and preserved Abase for the three tasks in PD. Using
      functional magnetic resonance imaging (fMRI) and diffusion tractography, we
      explored the neural substrates underlying speeded performance of the three tasks
      in healthy participants, suggesting the involvement of distinct BTC circuits in
      cognitive and motor agility. Language and motor BTC circuits were specifically
      active during speeded performance of the calculation and movement tasks,
      respectively, whereas premotor BTC circuits revealed activity for speeded
      performance of all tasks. Finally, PD showed reduced task rate-correlated
      activity in the language BTC circuits for speeded calculation, in the premotor
      BTC circuit for speeded imagery, and in the motor BTC circuits for speeded
      movement, as compared with controls. The present study casts light on the anatomo
      functional organization of the BTC circuits and their parallel roles in
      invigorating movement and cognition through a function of dopamine.

PMID- 29379874
TI  - Behavioral Changes in Mice Lacking Interleukin-33.
AB  - Interleukin (IL)-33 is a member of the IL-1 family of cytokines. IL-33 is
      expressed in nuclei and secreted as alarmin upon cellular damage to deliver a
      danger signal to the surrounding cells. Previous studies showed that IL-33 is
      expressed in the brain and that it is involved in neuroinflammatory and
      neurodegenerative processes in both humans and rodents. Nevertheless, the role of
      IL-33 in physiological brain function and behavior remains unclear. Here, we have
      investigated the behaviors of mice lacking IL-33 (Il33-/- mice). IL-33 is
      constitutively expressed throughout the adult mouse brain, mainly in
      oligodendrocyte-lineage cells and astrocytes. Notably, Il33-/- mice exhibited
      reduced anxiety-like behaviors in the elevated plus maze (EPM) and the open field
      test (OFT), as well as deficits in social novelty recognition, despite their
      intact sociability, in the three-chamber social interaction test. The
      immunoreactivity of c-Fos proteins, an indicator of neuronal activity, was
      altered in several brain regions implicated in anxiety-related behaviors, such as
      the medial prefrontal cortex (mPFC), amygdala, and piriform cortex (PCX), in Il33
      /- mice after the EPM. Altered c-Fos immunoreactivity in Il33-/- mice was not
      correlated with IL-33 expression in wild-type (WT) mice nor was IL-33 expression
      affected by the EPM in WT mice. Thus, our study has revealed that Il33-/- mice
      exhibit multiple behavioral deficits, such as reduced anxiety and impaired social
      recognition. Our findings also indicate that IL-33 may regulate the development
      and/or maturation of neuronal circuits, rather than control neuronal activities
      in adult brains.

PMID- 29379875
TI  - State-Based Delay Representation and Its Transfer from a Game of Pong to Reaching
      and Tracking.
AB  - To accurately estimate the state of the body, the nervous system needs to account
      for delays between signals from different sensory modalities. To investigate how
      such delays may be represented in the sensorimotor system, we asked human
      participants to play a virtual pong game in which the movement of the virtual
      paddle was delayed with respect to their hand movement. We tested the
      representation of this new mapping between the hand and the delayed paddle by
      examining transfer of adaptation to blind reaching and blind tracking tasks.
      These blind tasks enabled to capture the representation in feedforward mechanisms
      of movement control. A Time Representation of the delay is an estimation of the
      actual time lag between hand and paddle movements. A State Representation is a
      representation of delay using current state variables: the distance between the
      paddle and the ball originating from the delay may be considered as a spatial
      shift; the low sensitivity in the response of the paddle may be interpreted as a
      minifying gain; and the lag may be attributed to a mechanical resistance that
      influences paddle's movement. We found that the effects of prolonged exposure to
      the delayed feedback transferred to blind reaching and tracking tasks and caused
      participants to exhibit hypermetric movements. These results, together with
      simulations of our representation models, suggest that delay is not represented
      based on time, but rather as a spatial gain change in visuomotor mapping.

PMID- 29379877
TI  - Long-Term Visual Training Increases Visual Acuity and Long-Term Monocular
      Deprivation Promotes Ocular Dominance Plasticity in Adult Standard Cage-Raised
      Mice.
AB  - For routine behavioral tasks, mice predominantly rely on olfactory cues and
      tactile information. In contrast, their visual capabilities appear rather
      restricted, raising the question whether they can improve if vision gets more
      behaviorally relevant. We therefore performed long-term training using the visual
      water task (VWT): adult standard cage (SC)-raised mice were trained to swim
      toward a rewarded grating stimulus so that using visual information avoided
      excessive swimming toward nonrewarded stimuli. Indeed, and in contrast to old
      mice raised in a generally enriched environment (Greifzu et al., 2016), long-term
      VWT training increased visual acuity (VA) on average by more than 30% to 0.82
      cycles per degree (cyc/deg). In an individual animal, VA even increased to 1.49
      cyc/deg, i.e., beyond the rat range of VAs. Since visual experience enhances the
      spatial frequency threshold of the optomotor (OPT) reflex of the open eye after
      monocular deprivation (MD), we also quantified monocular vision after VWT
      training. Monocular VA did not increase reliably, and eye reopening did not
      initiate a decline to pre-MD values as observed by optomotry; VA values rather
      increased by continued VWT training. Thus, optomotry and VWT measure different
      parameters of mouse spatial vision. Finally, we tested whether long-term MD
      induced ocular dominance (OD) plasticity in the visual cortex of adult [postnatal
      day (P)162-P182] SC-raised mice. This was indeed the case: 40-50 days of MD
      induced OD shifts toward the open eye in both VWT-trained and, surprisingly, also
      in age-matched mice without VWT training. These data indicate that (1) long-term
      VWT training increases adult mouse VA, and (2) long-term MD induces OD shifts
      also in adult SC-raised mice.

PMID- 29379876
TI  - Back to Pupillometry: How Cortical Network State Fluctuations Tracked by Pupil
      Dynamics Could Explain Neural Signal Variability in Human Cognitive Neuroscience.
AB  - The mammalian thalamocortical system generates intrinsic activity reflecting
      different states of excitability, arising from changes in the membrane potentials
      of underlying neuronal networks. Fluctuations between these states occur
      spontaneously, regularly, and frequently throughout awake periods and influence
      stimulus encoding, information processing, and neuronal and behavioral responses.
      Changes of pupil size have recently been identified as a reliable marker of
      underlying neuronal membrane potential and thus can encode associated network
      state changes in rodent cortex. This suggests that pupillometry, a ubiquitous
      measure of pupil dilation in cognitive neuroscience, could be used as an index
      for network state fluctuations also for human brain signals. Considering this
      variable may explain task-independent variance in neuronal and behavioral signals
      that were previously disregarded as noise.

PMID- 29379878
TI  - Caveolin1 Identifies a Specific Subpopulation of Cerebral Cortex Callosal
      Projection Neurons (CPN) Including Dual Projecting Cortical Callosal/Frontal
      Projection Neurons (CPN/FPN).
AB  - The neocortex is composed of many distinct subtypes of neurons that must form
      precise subtype-specific connections to enable the cortex to perform complex
      functions. Callosal projection neurons (CPN) are the broad population of
      commissural neurons that connect the cerebral hemispheres via the corpus callosum
      (CC). Currently, how the remarkable diversity of CPN subtypes and connectivity is
      specified, and how they differentiate to form highly precise and specific
      circuits, are largely unknown. We identify in mouse that the lipid-bound
      scaffolding domain protein Caveolin 1 (CAV1) is specifically expressed by a
      unique subpopulation of Layer V CPN that maintain dual ipsilateral frontal
      projections to premotor cortex. CAV1 is expressed by over 80% of these dual
      projecting callosal/frontal projection neurons (CPN/FPN), with expression peaking
      early postnatally as axonal and dendritic targets are being reached and refined.
      CAV1 is localized to the soma and dendrites of CPN/FPN, a unique population of
      neurons that shares information both between hemispheres and with premotor
      cortex, suggesting function during postmitotic development and refinement of
      these neurons, rather than in their specification. Consistent with this, we find
      that Cav1 function is not necessary for the early specification of CPN/FPN, or
      for projecting to their dual axonal targets. CPN subtype-specific expression of
      Cav1 identifies and characterizes a first molecular component that distinguishes
      this functionally unique projection neuron population, a population that expands
      in primates, and is prototypical of additional dual and higher-order projection
      neuron subtypes.

PMID- 29379879
TI  - Activity-Dependent Inhibitory Synapse Scaling Is Determined by Gephyrin
      Phosphorylation and Subsequent Regulation of GABAA Receptor Diffusion.
AB  - Synaptic plasticity relies on the rapid changes in neurotransmitter receptor
      number at postsynaptic sites. Using superresolution photoactivatable localization
      microscopy imaging and quantum dot-based single-particle tracking in rat
      hippocampal cultured neurons, we investigated whether the phosphorylation status
      of the main scaffolding protein gephyrin influenced the organization of the
      gephyrin scaffold and GABAA receptor (GABAAR) membrane dynamics. We found that
      gephyrin phosphorylation regulates gephyrin microdomain compaction. Extracellular
      signal-regulated kinase 1/2 and glycogen synthase kinase 3beta (GSK3beta)
      signaling alter the gephyrin scaffold mesh differentially. Differences in
      scaffold organization similarly affected the diffusion of synaptic GABAARs,
      suggesting reduced gephyrin receptor-binding properties. In the context of
      synaptic scaling, our results identify a novel role of the GSK3beta signaling
      pathway in the activity-dependent regulation of extrasynaptic receptor surface
      trafficking and GSK3beta, protein kinase A, and calcium/calmodulin-dependent
      protein kinase IIalpha pathways in facilitating adaptations of synaptic
      receptors.

PMID- 29379880
TI  - The Variability of Neural Responses to Naturalistic Videos Change with Age and
      Sex.
AB  - Neural development is generally marked by an increase in the efficiency and
      diversity of neural processes. In a large sample (n = 114) of human children and
      adults with ages ranging from 5 to 44 yr, we investigated the neural responses to
      naturalistic video stimuli. Videos from both real-life classroom settings and
      Hollywood feature films were used to probe different aspects of attention and
      engagement. For all stimuli, older ages were marked by more variable neural
      responses. Variability was assessed by the intersubject correlation of evoked
      electroencephalographic responses. Young males also had less-variable responses
      than young females. These results were replicated in an independent cohort (n =
      303). When interpreted in the context of neural maturation, we conclude that
      neural function becomes more variable with maturity, at least during the passive
      viewing of real-world stimuli.

PMID- 29379881
TI  - Biallelic CHP1 mutation causes human autosomal recessive ataxia by impairing NHE1
      function.
AB  - Objective: To ascertain the genetic and functional basis of complex autosomal
      recessive cerebellar ataxia (ARCA) presented by 2 siblings of a consanguineous
      family characterized by motor neuropathy, cerebellar atrophy, spastic
      paraparesis, intellectual disability, and slow ocular saccades. Methods: Combined
      whole-genome linkage analysis, whole-exome sequencing, and focused screening for
      identification of potential causative genes were performed. Assessment of the
      functional consequences of the mutation on protein function via subcellular
      fractionation, size-exclusion chromatography, and fluorescence microscopy were
      done. A zebrafish model, using Morpholinos, was generated to study the pathogenic
      effect of the mutation in vivo. Results: We identified a biallelic 3-bp deletion
      (p.K19del) in CHP1 that cosegregates with the disease. Neither focused screening
      for CHP1 variants in 2 cohorts (ARCA: N = 319 and NeurOmics: N = 657) nor
      interrogating GeneMatcher yielded additional variants, thus revealing the
      scarcity of CHP1 mutations. We show that mutant CHP1 fails to integrate into
      functional protein complexes and is prone to aggregation, thereby leading to
      diminished levels of soluble CHP1 and reduced membrane targeting of NHE1, a major
      Na+/H+ exchanger implicated in syndromic ataxia-deafness. Chp1 deficiency in
      zebrafish, resembling the affected individuals, led to movement defects,
      cerebellar hypoplasia, and motor axon abnormalities, which were ameliorated by
      coinjection with wild-type, but not mutant, human CHP1 messenger RNA.
      Conclusions: Collectively, our results identified CHP1 as a novel ataxia
      causative gene in humans, further expanding the spectrum of ARCA-associated loci,
      and corroborated the crucial role of NHE1 within the pathogenesis of these
      disorders.

PMID- 29379883
TI  - Homozygous CAPN1 mutations causing a spastic-ataxia phenotype in 2 families.

PMID- 29379882
TI  - Alzheimer risk loci and associated neuropathology in a population-based study
      (Vantaa 85+).
AB  - Objective: To test the association of distinct neuropathologic features of
      Alzheimer disease (AD) with risk loci identified in genome-wide association
      studies. Methods: Vantaa 85+ is a population-based study that includes 601
      participants aged >=85 years, of which 256 were neuropathologically examined. We
      analyzed 29 AD risk loci in addition to APOE epsilon4, which was studied
      separately and used as a covariate. Genotyping was performed using a single
      nucleotide polymorphism (SNP) array (341 variants) and imputation (6,038
      variants). Participants with Consortium to Establish a Registry for Alzheimer
      Disease (CERAD) (neuritic Abeta plaques) scores 0 (n = 65) vs score M + F (n =
      171) and Braak (neurofibrillary tangle pathology) stages 0-II (n = 74) vs stages
      IV-VI (n = 119), and with capillary Abeta (CapAbeta, n = 77) vs without (n = 179)
      were compared. Cerebral amyloid angiopathy (CAA) percentage was analyzed as a
      continuous variable. Results: Altogether, 24 of the 29 loci were associated (at p
      < 0.05) with one or more AD-related neuropathologic features in either SNP array
      or imputation data. Fifteen loci associated with CERAD score, smallest p =
      0.0002122, odds ratio (OR) 2.67 (1.58-4.49) at MEF2C locus. Fifteen loci
      associated with Braak stage, smallest p = 0.004372, OR 0.31 (0.14-0.69) at GAB2
      locus. Twenty loci associated with CAA, smallest p = 7.17E-07, beta 14.4 (8.88
      20) at CR1 locus. Fifteen loci associated with CapAbeta smallest p = 0.002594, OR
      0.54 (0.37-0.81) at HLA-DRB1 locus. Certain loci associated with specific
      neuropathologic features. CASS4, CLU, and ZCWPW1 associated only with CAA, while
      TREM2 and HLA-DRB5 associated only with CapAbeta. Conclusions: AD risk loci
      differ in their association with neuropathologic features, and we show for the
      first time distinct risk loci for CAA and CapAbeta.

PMID- 29379884
TI  - 1q21.1 Duplication syndrome and epilepsy: Case report and review.

PMID- 29379885
TI  - A Novel Fluorescence-Based Assay for the Measurement of Biliverdin Reductase
      Activity.
AB  - Biliverdin reductase (BVR) is the enzyme responsible for the last step in the
      production of bilirubin from the breakdown of heme. Bilirubin is one of the most
      potent antioxidant molecules in the body. Monitoring BVR activity is essential in
      studying the antioxidant capacity of cells and tissues. Traditional methods of
      determining BVR activity have relied on the measurement of bilirubin converted
      from biliverdin using absorbance spectroscopy. The approach has limited
      sensitivity and requires large quantities of cells or tissues. We have developed
      a novel fluorescence-based method utilizing the eel protein, UnaG, for the
      detection of bilirubin produced by BVR. The UnaG protein only fluoresces by the
      induction of bilirubin. We have also used this approach to measure intracellular
      bilirubin content of cultured cells. We validated this assay using cell lysates
      from mouse liver and immortalized murine hepatic cell line (Hepa1c1c7) and kidney
      cell line (MCT) in which BVR isoform A (BVRA) was either knocked out via CRISPR
      or stably overexpressed by lentivirus. Also, we tested the method using
      previously reported putative BVRA inhibitors, Closantel and Ebselen. These
      studies show a new method for measuring bilirubin intracellularly and in lysates.

PMID- 29379886
TI  - Improving colorectal cancer referrals.
AB  - The colorectal services at The Royal Bournemouth Hospital needed to adapt to meet
      the extra demand on fast-track patient referrals to the outpatient department, as
      a consequence of the changes in the National Institute for Health and Care
      Excellence (NICE) guidance on cancer referrals in June 2015. Learning from other
      units, a telephone assessment clinic (TAC) triaging patients straight to
      colonoscopy was trialled. A Plan-Do-Study-Act (PDSA) methodology was used. A
      baseline study showed that fast-track colorectal patients referred from their
      general practitioner (GP) were taking on average 30 days until they received
      their colonoscopy. This quality improvement project focused on sending fast-track
      colorectal GP referrals through a straight-to-colonoscopy TAC. The results of
      this intervention showed an improvement from GP referral to colonoscopy. Both
      PDSA cycle 1 and PDSA cycle 2 showed an average of 24 days. This reduction of 6
      days was a promising improvement in a 62-day patient pathway, so funds were
      accessed to invest in a temporary full-time TAC nurse appointment to allow more
      data to be collected. PDSA cycle 3 showed a reduction of the average from
      referral to colonoscopy to 19 days and a reduction in the variation. This outcome
      will be sustainable, as the TAC role is now a permanent position.

PMID- 29379887
TI  - Quercetin inhibits adipogenesis of muscle progenitor cells in vitro.
AB  - Muscle satellite cells are committed myogenic progenitors capable of contributing
      to myogenesis to maintain adult muscle mass and function. Several experiments
      have demonstrated that muscle satellite cells can differentiate into adipocytes
      in vitro, supporting the mesenchymal differentiation potential of these cells.
      Moreover, muscle satellite cells may be a source of ectopic muscle adipocytes,
      explaining the lipid accumulation often observed in aged skeletal muscle
      (sarcopenia) and in muscles of patients' with diabetes. Quercetin, a polyphenol,
      is one of the most abundant flavonoids distributed in edible plants, such as
      onions and apples, and possesses antioxidant, anticancer, and anti-inflammatory
      properties. In this study, we examined whether quercetin inhibited the
      adipogenesis of muscle satellite cells in vitro with primary cells from rat limbs
      by culture in the presence of quercetin under adipogenic conditions.
      Morphological observations, Oil Red-O staining results, triglyceride content
      analysis, and quantitative reverse transcription polymerase chain reaction
      revealed that quercetin was capable of inhibiting the adipogenic induction of
      muscle satellite cells into adipocytes in a dose-dependent manner by suppressing
      the transcript levels of adipogenic markers, such as peroxisome proliferator
      activated receptor-gamma and fatty acid binding protein 4. Our results suggested
      that quercetin inhibited the adipogenesis of muscle satellite cells in vitro by
      suppressing the transcription of adipogenic markers.

PMID- 29379888
TI  - Factors associated with anxiety and depression in hospitalized patients with
      first episode of acute myocardial infarction.
AB  - Introduction: Evaluation of anxiety and depression in cardiac patients is an area
      of nursing practice that is frequently neglected. The aim of the study was to
      explore anxiety and depression in hospitalized patients with their first episode
      of acute myocardial infarction. Material and methods: The study sample included
      148 hospitalized patients who had a first episode of acute myocardial infarction.
      Data collection was performed by the interview method using a specially designed
      questionnaire which included socio-demographic, clinical and other patients'
      characteristics as well as the Hospital Anxiety and Depression Scale (HADS) to
      assess patients' levels of anxiety and depression. Results: Analysis of data
      showed that 52% and 38% of participants had high levels of anxiety and
      depression, respectively. Furthermore, anxiety levels revealed a statistically
      significant association with anxiolytics (p = 0.005) and antidepressant
      medication (p = 0.026) in hospital, the belief that they will face difficulties
      in relations with the social and family environment (p = 0.009 and p = 0.002,
      respectively) and whether they considered themselves anxious (p = 0.003).
      Depression was statistically significantly associated with education level (p =
      0.001), profession (p = 0.007), antidepressant medication in hospital (p <=
      0.001), patients' relations with nursing staff (p = 0.019) and patients' belief
      that they will face difficulties in relations with the social and family
      environment (p <= 0.001 and p <= 0.001, respectively). Conclusions: The results
      showed that socio-demographic and clinical characteristics should be taken into
      serious consideration when exploring anxiety and depression in patients with a
      first episode of acute myocardial infarction in order to implement appropriate
      interventions.

PMID- 29379889
TI  - A unique reason for coronary spasm causing temporary ST elevation myocardial
      infarction (inferior STEMI) - systemic inflammatory response syndrome after use
      of pembrolizumab.

PMID- 29379890
TI  - Do standard carotid artery endarterectomy and primary closure technique cause
      early restenosis in diabetic patients?
AB  - Introduction: We aimed to investigate carotid restenosis in 2-year follow-up in
      diabetic and nondiabetic patients who underwent standard carotid endarterectomy
      with primary carotid closure and determine whether diabetes mellitus is a risk
      factor for early stenosis for this surgical procedure. Material and methods: We
      retrospectively assessed the data of patients who underwent standard carotid
      endarterectomy with primary carotid closure from the hospital registry and
      outpatient clinic follow-up between January 2006 and January 2012. The study
      included 25 diabetics and 25 nondiabetics, in total 50 patients. The control
      carotid Doppler ultrasonographies and/or computed tomography angiographies of the
      patients at postoperative 1, 6, 12, and 24 months were examined and a stenosis
      rate between 70% and 99% was regarded as significant carotid restenosis. Results:
      When the diabetic and nondiabetic group patients were compared for early carotid
      restenosis at 2 years, there were 3 (12%) patients in the diabetic group and 4
      (16%) patients in the nondiabetic group with restenosis. A statistically
      significant difference in early carotid restenosis was not observed between the
      two groups (p > 0.05). Conclusions: Standard carotid endarterectomy and primary
      closure of the artery is a successfully performed surgical procedure in diabetic
      patients. We concluded that diabetes mellitus is not a risk factor for early
      restenosis in the diabetic patient population according to the results of our
      research.

PMID- 29379891
TI  - Non-hemorrhage-related adverse effects of rivaroxaban.
AB  - The direct oral anticoagulant rivaroxaban is useful in various indications that
      include venous deep vein thrombosis prophylaxis/treatment after knee/hip
      replacement surgery and prevention of stroke in patients with non-valvular atrial
      fibrillation. Its mechanism of action has been mostly associated with hemorrhage
      related adverse effects; thus a number of non-hemorrhage-related adverse effects
      of the drug have received less attention or go unrecognized. These adverse
      effects mainly include liver injury, hypersensitivity reactions, leukocytoclastic
      vasculitis and hair loss. Clinicians should be aware of these rare adverse
      reactions and advise their patients to contact them as soon as they observe any
      unexpected clinical response.

PMID- 29379892
TI  - (Epi)genotype-Phenotype Analysis in 69 Japanese Patients With
      Pseudohypoparathyroidism Type I.
AB  - Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with
      Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright
      hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically
      caused by genetic defects involving alpha subunit of the stimulatory G protein
      (Gsalpha)-coding GNAS exons and methylation defects of the GNAS differentially
      methylated regions (DMRs) on the maternal allele, respectively, detailed
      phenotypic characteristics still remains to be examined. Objective: To clarify
      phenotypic characteristics according to underlying (epi)genetic causes. Patients
      and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese
      patients with PHP-I; that is, 28 patients with genetic defects involving Gsalpha
      coding GNAS exons (group 1) consisting of 12 patients with missense variants
      (subgroup A) and 16 patients with null variants (subgroup B), as well as 41
      patients with methylation defects (group 2) consisting of 21 patients with broad
      methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an
      isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion
      (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly
      similar to those reported previously, several important findings were identified,
      including younger age at hypocalcemic symptoms and higher frequencies of
      hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly
      in four patients of subgroup C, predominant manifestation of subcutaneous
      ossification in subgroup B, higher frequency of thyrotropin resistance in group 1
      than in group 2, and relatively low thyrotropin values in four patients with low
      T4 values and relatively low luteinizing hormone/follicle-stimulating hormone
      values in five adult females with ovarian dysfunction. Conclusion: The results
      imply the presence of clinical findings characteristic of each underlying cause
      and provide useful information on the imprinting status of Gsalpha.

PMID- 29379893
TI  - The Orphan Nuclear Receptor Liver Homolog Receptor-1 (Nr5a2) Regulates Ovarian
      Granulosa Cell Proliferation.
AB  - In mouse ovaries, liver receptor homolog-1 [nuclear receptor subfamily 5, group
      A, member 2 (Nr5a2)] expression is restricted to granulosa cells. Mice with Nr5a2
      depletion in this cell population fail to ovulate. To determine whether Nr5a2 is
      essential for granulosa cell proliferation during follicular maturation, we
      generated granulosa-specific conditional knockout mice (genotype Nr5a2 floxed Cre
      recombinase driven by the anti-Mullerian type II receptor, hereafter cKO) with
      Nr5a2 depletion from primary follicles forward. Proliferation in cKO granulosa
      cells was substantially reduced relative to control (CON) counterparts, as
      assessed by bromodeoxyuridine incorporation, proliferative cell nuclear antigen
      expression, and fluorescent-activated cell sorting. Microarray analysis revealed
      >2000 differentially regulated transcripts between cKO and CON granulosa cells.
      Major gene ontology pathways disrupted were proliferation, steroid biosynthesis,
      female gamete formation, and ovulatory cycle. Transcripts for key cell-cycle
      genes, including Ccnd1, Ccnd2, Ccne1, Ccne2, E2f1, and E2f2, were in reduced
      abundance. Transcripts from other cell-cycle-related factors, including Cdh2,
      Plagl1, Cdkn1a, Prkar2b, Gstm1, Cdk7, and Pts, were overexpressed. Although the
      follicle-stimulating hormone and estrogen receptors were overexpressed in the cKO
      animals, in vivo treatment with estradiol-17beta failed to rescue decreased
      proliferation. In vitro inactivation of Nr5a2 using the ML180 reverse agonist
      similarly decreased cell-cycle-related gene transcripts and downstream targets,
      as in cKO mice. Pharmacological inhibition of beta-catenin, an Nr5a2 cofactor,
      decreased cyclin gene transcripts and downstream targets. Terminal
      deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling
      immunofluorescence and quantitative polymerase chain reaction of
      pro/antiapoptotic and autophagic markers showed no differences between cKO and
      CON granulosa cells. Thus, Nr5a2 is essential for granulosa cell proliferation,
      but its depletion does not alter the frequency of apoptosis nor autophagy.

PMID- 29379894
TI  - Long-Acting GLP-1 Receptor Agonist Exenatide Influence on the Autonomic Cardiac
      Sympatho-Vagal Balance.
AB  - Long-acting glucagon-like peptide 1 receptor agonists are increasingly used to
      treat type 2 diabetes. An increase of heart rate (HR) has been observed with
      their use. To elucidate the role of the cardiac sympatho-vagal balance as a
      possible mediator of the reported increase in HR, we performed power spectral
      analysis of HR variability (HRV) in patients receiving exenatide extended-release
      (ER). Twenty-eight ambulatory patients with type 2 diabetes underwent evaluation
      at initiation of exenatide-ER and thereafter at 3 and at 6 months. To obtain
      spectral analyses of HRV, a computerized acquisition of 10 minutes of RR
      electrocardiogram intervals (mean values of ~700 RR intervals) were recorded both
      in lying and in standing positions. All patients showed a substantial increase of
      HR both in lying and in standing positions. Systolic blood pressure, body weight,
      and glycated hemoglobin A1c significantly decreased both at 3 and 6 months
      compared with basal levels. The low-frequency/high-frequency ratio varied from
      3.05 +/- 0.4 to 1.64 +/- 0.2 (P < 0.001) after 3 months and to 1.57 +/- 0.3 (P <
      0.001) after 6 months in a lying position and from 4.56 +/- 0.8 to 2.24 +/- 0.3
      (P < 0.001) after 3 months and to 2.38 +/- 0.4 (P < 0.001) after 6 months in a
      standing position compared with basal values, respectively. HR variations,
      induced by exenatide-ER treatment, do not appear to be related to sympathetic
      autonomic tone. Of note, we observed a relative increase of vagal influence on
      the heart.

PMID- 29379895
TI  - Aberrant Iodine Autoregulation Induces Hypothyroidism in a Mouse Strain in the
      Absence of Thyroid Autoimmunity.
AB  - We investigated factors underlying the varying effects of a high dietary iodide
      intake on serum T4 levels in a wide spectrum of mouse strains, including
      thyroiditis-susceptible NOD.H2h4, NOD.H2k, and NOD mice, as well as other strains
      (BALB/c, C57BL/6, NOD.Lc7, and B10.A4R) not previously investigated. Mice were
      maintained for up to 8 months on control or iodide-supplemented water (NaI
      0.05%). On iodized water, serum T4 was reduced in BALB/c (males and females) in
      association with colloid goiters but was not significantly changed in mice that
      developed thyroiditis, namely NOD.H2h4 (males and females) or male NOD.H2k mice.
      Neither goiters nor decreased T4 developed in C57BL/6, NOD, NOD.Lc7, or B10.A4R
      female mice. In further studies, we focused on males in the BALB/c and NOD.H2h4
      strains that demonstrated a large divergence in the T4 response to excess iodide.
      Excess iodide ingestion increased serum TSH levels to the same extent in both
      strains, yet thyroidal sodium iodide symporter (NIS) messenger RNA (mRNA) levels
      (quantitative polymerase chain reaction) revealed greatly divergent responses.
      NOD.H2h4 mice that remained euthyroid displayed a physiological NIS iodine
      autoregulatory response, whereas NIS mRNA was inappropriately elevated in BALB/c
      mice that became hypothyroid. Thus, autoimmune thyroiditis-prone NOD.H2h4 mice
      adapted normally to a high iodide intake, presumably by escape from the Wolff
      Chaikoff block. In contrast, BALB/c mice that did not spontaneously develop
      thyroiditis failed to escape from this block and became hypothyroid. These data
      in mice may provide insight into the mechanism by which iodide-induced
      hypothyroidism occurs in some humans without an underlying thyroid disorder.

PMID- 29379896
TI  - Single-Nucleotide Variations of the Human Nuclear Hormone Receptor Genes in
      60,000 Individuals.
AB  - Nuclear hormone receptors (NRs) mediate biologic actions of lipophilic molecules
      to gene transcription and are phylogenetically and functionally categorized into
      seven subfamilies and three groups, respectively. Single-nucleotide variations
      (SNVs) or polymorphisms are genetic changes influencing individual response to
      environmental factors and susceptibility to various disorders, and are part of
      the genetic diversification and basis for evolution. We sorted out SNVs of the
      human NR genes from 60,706 individuals, calculated three parameters (percentage
      of all variants, percentage of loss-of-function variants, and ratio of
      nonsynonymous/synonymous variants in their full protein-coding or major domain
      coding sequences), and compared them with several valuables. Comparison of these
      parameters between NRs and control groups identified that NRs form a highly
      conserved gene family. The three parameters for the full coding sequence are
      positively correlated with each other, whereas four NR genes are distinct from
      the others with much higher tolerance to protein sequence-changing variants. DNA
      binding domain and N-terminal domain are respectively those bearing the least and
      the most variation. NR subfamilies based on their phylogenetic proximity or
      functionality as well as diversity of tissue distribution and numbers of partner
      molecules are all not correlated with the variation parameters, whereas their
      gene age demonstrates an association. Our results suggest that the natural
      selection driving the NR family evolution still operates in humans. Gene age and
      probably the potential to adapt to various new ligands, but not current
      functional diversity, are major determinants for SNVs of the human NR genes.

PMID- 29379897
TI  - Effect of Growth Hormone on Uterine Receptivity in Women With Repeated
      Implantation Failure in an Oocyte Donation Program: A Randomized Controlled
      Trial.
AB  - Background and Objective: Administration of growth hormone (GH) during ovarian
      stimulation has been shown to improve success rates of in vitro fertilization. GH
      beneficial effect on oocyte quality is shown in several studies, but GH effect on
      uterine receptivity is not clear. To assess it, we studied whether GH
      administration can improve the chance of pregnancy and birth in women who
      experienced repeated implantation failure (RIF) using donated oocyte programs.
      Design and Study Population: A total of 105 infertile women were enrolled in the
      randomized controlled trial: 70 women were with a history of RIF with donated
      oocytes, and 35 infertile women underwent the first oocyte donation attempt.
      Women receiving donated oocytes were treated with progressively increasing doses
      of oral estradiol, followed by intravaginal progesterone after previous pituitary
      desensitization with gonadotropin-releasing hormone agonist. Thirty-five RIF
      patients were treated with GH (GH patients), whereas the rest of the 35 RIF
      patients (non-GH patients) and 35 first-attempt patients (positive control group)
      were not. Results: RIF patients receiving GH showed significantly thicker
      endometrium and higher pregnancy and live birth rates as compared with RIF
      patients of non-GH study group, although these rates remained somewhat lower as
      compared with the non-RIF patients of the positive control group. No abnormality
      was detected in any of the babies born. Conclusion: Our data of improved
      implantation, pregnancy, and live birth rates among infertile RIF patients
      treated with GH indicate that GH improves uterine receptivity.

PMID- 29379898
TI  - Anti-Ma-1 and Anti-Ma-2 Antibodies in Isolated Fatal Hypothalamitis.
AB  - Lymphocytic hypothalamitis (LHT) is a rare disease characterized by pituitary
      dysfunction, autonomic instability, metabolic disturbances, and neuropsychiatric
      disorders. We report the case of a 30-year-old man found to have LHT that
      progressed despite treatment with methylprednisolone and intravenous
      immunoglobulin (IVIG). A literature review was conducted to identify prior
      studies pertaining to LHT. Our patient presented with several weeks of fatigue,
      cold intolerance, weight loss, confusion, and headache. Laboratory tests were
      consistent with panhypopituitarism. Brain magnetic resonance imaging revealed an
      infiltrative enhancing mass in the area of the hypothalamus, and stereotactic
      biopsy findings showed reactive inflammatory changes. A course of hormone
      replacement (levothyroxine), methylprednisolone, and IVIG was initiated. The
      patient's course was complicated by a fatal tonsillar herniation. Autopsy
      revealed LHT. The diagnosis and management of autoimmune LHT are challenging. The
      entity should be considered in the setting of panhypopituitarism with a
      hypothalamic mass. Differentiating paraneoplastic and nonparaneoplastic
      hypothalamitis should be established for management and prognosis. Definitive
      treatment remains unclear; treatment with corticosteroids should be attempted,
      followed by consideration of other immunosuppressive agents, such as rituximab.
      If a paraneoplastic syndrome is suspected, management should also be directed
      toward the primary tumor.

PMID- 29379899
TI  - Fast Geodesic Regression for Population-Based Image Analysis.
AB  - Geodesic regression on images enables studies of brain development and
      degeneration, disease progression, and tumor growth. The high-dimensional nature
      of image data presents significant computational challenges for the current
      regression approaches and prohibits large scale studies. In this paper, we
      present a fast geodesic regression method that dramatically decreases the
      computational cost of the inference procedure while maintaining prediction
      accuracy. We employ an efficient low dimensional representation of diffeomorphic
      transformations derived from the image data and characterize the regressed
      trajectory in the space of diffeomorphisms by its initial conditions, i.e., an
      initial image template and an initial velocity field computed as a weighted
      average of pairwise diffeomorphic image registration results. This construction
      is achieved by using a first-order approximation of pairwise distances between
      images. We demonstrate the efficiency of our model on a set of 3D brain MRI scans
      from the OASIS dataset and show that it is dramatically faster than the state-of
      the-art regression methods while producing equally good regression results on the
      large subject cohort.

PMID- 29379900
TI  - Guest Editorial: Key to making great smiles... still our ceramists.

PMID- 29379901
TI  - EAED patient examination recommendations for interdisciplinary treatment
      planning.

PMID- 29379902
TI  - Conservative restoration of the worn dentition - the anatomically driven direct
      approach (ADA).
AB  - The treatment or management of tooth wear with composite resins can be
      challenging because significant alterations in the patient's occlusion are
      usually required. Comprehensive approaches include the use of facebows,
      articulator-mounted casts, laboratory-made wax-ups, and silicone indexes to
      deliver the restorations. Even though this sequence of steps is recommended, in
      many cases it is not applied. The reason for this is related to the complexity
      and time required for these steps, which are normally applied in indirect
      restorations like ceramics but not properly used in direct composite resin
      rehabilitations. Moreover, a large portion of these patients, clinicians, and
      technicians in many countries may not have the resources and/or tools to
      undertake a full comprehensive approach. In order to aid clinicians to use an
      exclusively direct method to manage these patients for whatever reasons, the
      authors propose in this article a thought process applied to diagnosis and
      treatment planning that allows the restoration of extensively worn dentitions in
      a logical clinical sequence. The first goal is to provide a clear and organized
      vision of the functional, biologic, and esthetic principles of treatment planning
      based on the most current, evidence-based notions and clarified insights from
      experts. These are principles that should be applied universally in any
      comprehensive treatment plan. The second goal is to propose the application of
      these principles to direct restorations even when no individualized articulator
      mounting or appropriate laboratory wax-ups are available - the anatomically
      driven direct approach (ADA).

PMID- 29379903
TI  - CAD/CAM-based chairside restorative technique with composite resin for full-mouth
      adhesive rehabilitation of excessively worn dentition.
AB  - Since the first introduction of the Cerec system (Sirona) in the early 1980s, the
      use of computer-aided design/computer-aided manufacture (CAD/CAM) technology has
      spread widely in modern adhesive dentistry. Thanks to this innovative technology,
      it has been possible to carry out chairside restorations fully managed by the
      clinician, with the advantages of lower costs for the patient, more rapid
      execution of the restorations, and the exclusion of the provisional phase. With
      further improvements in chairside technologies and materials, specifically in the
      field of composite resin blocks, it is now possible to fabricate multiple
      ultrathin, minimally invasive or even noninvasive restorations in one single
      appointment. The clinical case presented here was solved using an innovative
      approach: It was entirely studied and realized chairside by a dentist on a
      computer, without any plaster cast or classic articulator. Vertical dimension of
      occlusion (VDO) augmentation was projected with the 'Incisal Tip' tool on the
      virtual articulator of the Cerec system. Eight composite resin overlays were
      designed on the non-prepared posterior teeth of a patient suffering from
      generalized tooth loss principally caused by a history of bulimia nervosa. The
      maxillary anterior teeth were restored with six palatal veneers modified with
      direct composites from the vestibular side, in order to improve the esthetic
      integration of the restorations. The mandibular posterior teeth were built up
      with direct composites.

PMID- 29379904
TI  - Complete denture fabrication with CAD/CAM technology: a case report.
AB  - Demographers agree that the so-called elderly population will increase steadily
      in the future. Not only will their numbers increase, but they will live to an
      older age. In the case of fully edentulous patients, implant treatment is a
      possibility, but for many, rehabilitation by means of full removable dentures is
      still the preferred option. In recent decades, computer-aided design/computer
      aided manufacturing (CAD/CAM) has brought about what can only be described as a
      revolution in dental offices and dental laboratories. CAD/CAM has many areas of
      application, and these are constantly increasing. In response to the growing
      demand from users, CAD/CAM can now produce sets of complete removable dentures
      using a virtual design and fabrication process. A protocol for a new CAD/CAM
      supported method is presented here in a clinical case report. Laboratory
      procedures are simplified because a number of the conventional steps have now
      disappeared. Today, it is possible to design the shape of the teeth for each
      patient, which results in a better customization of the dentures. Combined with
      appropriate staining of the teeth and denture base, this method produces full
      removable dentures that integrate very well into the patient's face to ensure a
      good esthetic result.

PMID- 29379905
TI  - Preheated composite resin used as a luting agent for indirect restorations:
      effects on bond strength and resin-dentin interfaces.
AB  - PURPOSE: The aim of this study was to evaluate the effect of preheating composite
      resins used as luting agents for indirect restorations on microtensile bond
      strength (uTBS) and adhesive interfaces. MATERIAL AND METHODS: Fifty sound
      extracted third molars were used. Ten experimental groups were formed with three
      different luting agents: one resin cement (RelyX ARC) and two composite resins
      (Venus and Z250 XT). The composite resins were tested both at room temperature
      and when preheated to 64 degrees C. Restoration depth was tested using 2 or 4 mm
      height indirect composite resin restorations, previously made on cylindrical
      molds. Adhesive and luting procedures were done under simulated pulpal pressure.
      After luting, the teeth were sectioned into beams with a cross-sectional area of
      1 mm2 at the bonded interface, and tested in tension at 0.5 mm/min. The
      characteristics of the adhesive interfaces were observed under scanning electron
      microscopy (SEM). The uTBS data were analyzed using ANOVA and the Tukey test
      (alpha = 0.05). RESULTS: When luting 2 mm restorations, the composite resin Z250
      XT, preheated or at room temperature, achieved significantly higher uTBS than did
      RelyX ARC. At this depth, Venus did not differ from the resin cement, and with
      the 4 mm restorations, only preheated Venus presented significantly higher uTBS
      than RelyX ARC. Preheating the composite resin resulted in thinner luting
      interfaces, with a more intimate interaction between luting agent and adhesive
      layer. CONCLUSION: Preheating composite resin for luting procedures may not
      improve uTBS, although it could be used to reduce material viscosity and improve
      restoration setting.

PMID- 29379906
TI  - Color match of luting composites and try-in pastes: the impact on the final color
      of CAD/CAM lithium disilicate restorations.
AB  - AIM: Color matching of the restoration to the adjacent teeth can be difficult due
      to the translucency of the ceramic and the visual exposure of the polymerized
      resin cement through the ceramic material. The aim of this study was to identify
      color differences between try-in pastes and the corresponding luting resin
      composites. MATERIALS AND METHODS: The materials tested were Variolink Veneer,
      Variolink Try-In, Variolink Esthetic LC, and Variolink Esthetic Try-In. Blocks of
      IPS e.max CAD were bisected along the vertical axis, producing specimens of
      different thicknesses. The surfaces to be evaluated were finely polished with a
      metallographic machine using 6000 grit SiC paper. The IPS e.max CAD specimens
      cemented with resin cement or with the try-in pastes were superimposed on a resin
      composite specimen reproducing the tooth structure. Evaluation of the color
      differences between the try-in pastes and polymerized cements of the same shade
      was performed with a spectrophotometer and a visual evaluation by three
      observers. RESULTS: The measurements showed that for shades of Variolink Veneer
      and Variolink Esthetic LC resin cements and the corresponding try-in pastes there
      were significant color differences (DeltaE > 2.23). Among the groups of different
      thicknesses, specimens of 0.5-mm thickness exhibited the highest DeltaE values,
      while the specimens of 2-mm thickness exhibited the lowest. CONCLUSIONS: The
      present study suggests that dentists should not rely on try-in pastes for the
      final color evaluation because they do not perfectly match the color shade of the
      cement used for the final luting of ceramic restorations. The originality of this
      study was the interpretation of color differences utilizing both a scientific
      spectrophotometer and visual observation.

PMID- 29379907
TI  - Effects of ceramic layer thickness, cement color, and abutment tooth color on
      color reproduction of feldspathic veneers.
AB  - AIM: To optimize the esthetics of ceramic restorations, it is important to
      determine accurately the effects of various parameters on the final color of the
      restoration. However, there is a lack of information on what determines the color
      of translucent feldspathic veneers formed using ceramics such as Vita Mark II.
      The aim of this study was to evaluate the effects of the ceramic layer thickness,
      cement color, and abutment tooth color on the color of the feldspathic ceramic
      veneer restoration. MATERIAL AND METHODS: A total of 30 all-ceramic monolithic
      veneers (Vita Mark II) were fabricated using a CAD/CAM system. The crowns were
      divided into three groups of differing ceramic thickness (0.4-, 0.7-, and 1.0-mm
      thick). Each type of crown was seated on six different-colored abutment teeth
      (1M1 [reference], 1M2, 2M2, 3M2, 4M2, and 5M2) using seven different try-in paste
      colors. The color of the resulting restoration was evaluated using
      spectrophotometry with a spot-measurement device (Vita Easyshade Advance 4.0).
      Color data are expressed in CIE L*a*b* system coordinates, and color differences
      DeltaE relative to the reference tooth were calculated and analyzed using one-way
      analysis of variance (ANOVA) with the Bonferroni post hoc test at alpha = 0.05.
      RESULTS: The color difference DeltaE of the feldspathic all-ceramic veneer system
      was significantly affected by the thickness of the ceramic layer, the cement
      color, and the abutment tooth color (P < 0.05). The smallest values of DeltaE
      compared with the reference color were found when try-in pastes shade -3 was
      used. As the thickness of the ceramic layer increased, a significant decrease in
      DeltaE was found. As the color of the abutment tooth varied from light to dark, a
      significant increase was found in DeltaE. CONCLUSION: The thickness of the
      ceramic layer, the cement color, and the abutment tooth color significantly
      affected the color of the resulting CAD/CAM feldspathic ceramic veneer
      restoration.

PMID- 29379908
TI  - Microfluidic ELISA employing an enzyme substrate and product species with similar
      detection properties.
AB  - The requirement for an enzyme label to carry out a chemical reaction directly at
      the signaling region of the enzyme substrate in order to produce a large change
      in its detectability places a significant constraint on the scope of enzyme
      linked immunosorbent assays (ELISAs). In particular, this requirement limits the
      kinds of enzyme label-substrate couples employable in ELISAs and prevents their
      independent optimization with respect to the enzyme reaction and the
      detectability of the enzyme reaction substrate/product. The detection limit and
      multiplexing capabilities of the assay are consequently restricted in addition to
      rendering the technique applicable to a narrow range of assay conditions/samples.
      Attempting to address some of these limitations, the current article describes a
      microfluidic ELISA method that does not require the enzyme label to act around
      the signaling region of the substrate molecule. A highly detectable rhodamine
      based substrate was synthesized to demonstrate the reported assay which upon
      cleavage by the enzyme label, alkaline phosphatase, transformed from a
      monoanionic to a monocationic species, both of which had nearly identical
      fluorescence properties. These species were later separated based on their charge
      difference using capillary zone electrophoresis in an integrated device yielding
      a quantitative measure for the analyte (human TNF-alpha) in our sample.
      Impressively, the noted approach not only enabled the use of a new kind of enzyme
      substrate for ELISAs but also allowed the detection of human TNF-alpha at
      concentrations over 54-fold lower than that possible on commercial microwell
      plates primarily due to the better detectability of the rhodamine dye.

PMID- 29379909
TI  - Identification of isoforms of aspartic acid residues in peptides by 2D UV-MS
      fingerprinting of cold ions.
AB  - We use 2D UV-MS cold-ion spectroscopy for the identification of l-Asp, d-Asp, l
      isoAsp and d-isoAsp residues in a fragment peptide derived from the hormone
      protein amylin. Relative solution concentrations of all four isoforms in an
      equimolar quaternary mixture have been determined within 4% error. This method
      demonstrates that for binary mixtures of the peptides an accuracy of 2.5% can be
      reached in few-second measurements.

PMID- 29379910
TI  - Nanocomposite injectable gels capable of self-replenishing regenerative
      extracellular microenvironments for in vivo tissue engineering.
AB  - Injectable hydrogels are biomaterials that have the potential to provide
      scaffolds to cells for in situ tissue regeneration with a minimally invasive
      implantation procedure. The success of in vivo tissue engineering utilizing
      injectable gels depends on providing cells with appropriate scaffolds that
      present an instructive extracellular microenvironment, which strongly influences
      the survival, proliferation, organization, and function of cells encapsulated
      within gels. One of the most important abilities of injectable gels to achieve
      this function is to adsorb and retain a wide variety of requisite bioactive
      molecules including nutrients, extracellular matrices, and growth/differentiation
      factors within gels. Previously, we developed nanocomposite injectable gels
      fabricated by simple combination of common biodegradable copolymers, poly(lactide
      co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG
      PLGA), and synthetic clay nanoparticles (LAPONITE(r)). We revealed that the
      nanocomposite injectable gels strongly adsorb ECM molecules including collagen
      and heparin within gels and retain them due to the ability of LAPONITE(r) in
      synchronization with the degradation of PLGA-PEG-PLGA and subsequent release of
      the degradation products. Human dermal fibroblast cells cultured on the
      nanocomposite gels showed enough high cell viability and proliferation for at
      least a week. Moreover, various kinds of human cells encapsulated within the
      nanocomposite gels exhibited significantly higher survival, proliferation, and
      three-dimensional organization in comparison with the PLGA-PEG-PLGA gel,
      LAPONITE(r) gel, and Matrigel. Furthermore, transplantation of mouse myoblast
      cells with the nanocomposite gels in model mice of skeletal muscle injury
      dramatically enhanced tissue regeneration and functional recovery, whereas cell
      transplantation with the PLGA-PEG-PLGA gel did not. Thus, the nanocomposite
      injectable gels possess unique abilities to self-replenish the regenerative
      extracellular microenvironment within the gels in the body, demonstrating the
      potential utility of the nanocomposite injectable gels for in vivo tissue
      engineering.

PMID- 29379911
TI  - A rapid and specific bacterial detection method based on cell-imprinted
      microplates.
AB  - Bacterial detection has attracted substantial interest in recent years owing to
      its importance in biology, medical care, drug discovery, and public health. For
      such applications, bacterial cell-imprinting technologies are regarded as
      potential methods, as they can fabricate artificial tailor-made receptors for
      cellular recognition. In comparison to conventional methods, which generally
      require a few days for bacterial determination, cell-imprinted polymers can save
      a substantial amount of time. Here, we report a high-throughput bacterial
      detection method based on a cell-imprinted 96-well microplate. The fabrication of
      the bacterial cell-imprinted polypyrrole and nafion complex was accomplished on a
      gold nanoparticle-coated microplate. The cell-imprinted polymer complex on the
      microplate can spontaneously rebind and specifically detect target cells with
      high selectivity in a short time frame (within 30 min). Furthermore, the
      microplates could discriminate particular target Escherichia coli O157:H7 cells
      from bacterial mixtures. This simple method may be used for a variety of
      applications such as clinical testing, food safety, and continuous environmental
      monitoring.

PMID- 29379912
TI  - An [Mn2(bpmp)]3+ complex as an artificial peroxidase and its applications in
      colorimetric pyrophosphate sensing and cascade-type pyrophosphatase assay.
AB  - The development of artificial peroxidases has attracted great interest because of
      their applications in various fields such as the chemical industry and
      biosensing. In this study, 2,6-bis[(bis(2-pyridylmethyl)amino)-methyl]-4
      methylphenol (H-bpmp) complexes with various transition metal ions have been
      investigated as artificial peroxidases. Among these metal complexes, the
      [Mn2(bpmp)]3+ complex showed the highest peroxidase-like activity as determined
      by a colorimetric assay using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic
      acid) (ABTS) and H2O2. The peroxidase-like activity was inhibited by
      pyrophosphate (PPi), which blocked the active site of the [Mn2(bpmp)]3+ complex.
      Based on this phenomenon, the ABTS/H2O2/[Mn2(bpmp)]3+ system could be applied for
      the detection of PPi, which could be achieved selectively by visual observation
      with a detection limit of 130 nM. Moreover, the addition of pyrophosphatase
      (PPase) to the [Mn2(bpmp)]3+ complex blocked by PPi resulted in the recovery of
      the peroxidase-like activity of the [Mn2(bpmp)]3+ complex due to the hydrolysis
      of PPi. Hence, the enzyme cascade reaction of the PPase and [Mn2(bpmp)]3+ complex
      allowed the real-time colorimetric assay of PPase.

PMID- 29379914
TI  - Palladium-catalyzed primary amine-directed regioselective mono- and di
      alkynylation of biaryl-2-amines.
AB  - The first example of the palladium-catalyzed primary amine-directed C(sp2)-H
      alkynylation of biaryl-2-amines has been developed by using
      (bromoethynyl)triisopropylsilane as an alkynylating reagent. This protocol
      exhibits a broad substrate scope, excellent regioselectivity and gram-scale
      synthesis. Significantly, the versatility of this straightforward method was
      further demonstrated by controlled mono- and di-alkynylation.

PMID- 29379913
TI  - The synthesis of LA-Fe3O4@PDA-PEG-DOX for photothermal therapy-chemotherapy.
AB  - A facile methodology is presented to construct a multifunctional nanocomposite
      that integrates photothermal therapy and specific drug release into a single
      nanostructure. Firstly, magnetic Fe3O4@polydopamine core-shell nanoparticles
      (Fe3O4@PDA) were synthesized via a reversed-phase microemulsion approach. By
      varying the amount of DA, Fe3O4@PDA with a particle size of 28-38 nm can be
      obtained. To further ensure the monodispersity, biocompatibility and specific
      uptake, PEG and lactobionic acid (LA) were grafted onto Fe3O4@PDA (LA-Fe3O4@PDA
      PEG), whose fast photothermal conversion is derived by the combination of Fe3O4
      and PDA with high near infrared (NIR) absorption. Then, doxorubicin hydrochloride
      (DOX) was adopted as the typical anticancer drug, which was loaded onto LA
      Fe3O4@PDA-PEG via electrostatic and pi-pi stacking interaction. The release
      kinetics investigation further demonstrated the acid/heat-triggered DOX release.
      HepG2 cells (hepatocellular cell line) were used as the target cancer cells, and
      the fast uptake was due to the nanoparticle size and abundant asialoglycoprotein
      receptors on HepG2 cells. Besides, an external magnetic field also can improve
      the uptake, especially when the magnet is placed at the bottom of the cell disk.
      The enhanced specific cytotoxicity toward HepG2 cells was also ascribed to the
      synergistic effect of chemo- and photothermal therapy. Based on the novel
      properties, the LA-Fe3O4@PDA-PEG-DOX nanocomposite showed its potential
      application in hepatocyte therapy.

PMID- 29379915
TI  - Controllable assembly of the benzothiazole framework using a C[triple bond,
      length as m-dash]C triple bond as a one-carbon synthon.
AB  - A concise and efficient protocol to assemble diverse benzothiazole derivatives in
      high yields was provided via copper catalyzed tandem cyclization with o
      haloanilines, elemental sulfur and terminal alkynes as raw materials. In this
      protocol, C atoms on the C[triple bond, length as m-dash]C triple bond were
      controllably involved in the construction of the benzothiazole framework and
      multiple carbon-heteroatom bonds through divergent routes.

PMID- 29379916
TI  - Recent advances in spectroelectrochemistry.
AB  - The integration of two quite different techniques, conventional electrochemistry
      and spectroscopy, into spectroelectrochemistry (SEC) provides a complete
      description of chemically driven electron transfer processes and redox events for
      different kinds of molecules and nanoparticles. SEC possesses interdisciplinary
      advantages and can further expand the scopes in the fields of analysis and other
      applications, emphasizing the hot issues of analytical chemistry, materials
      science, biophysics, chemical biology, and so on. Considering the past and future
      development of SEC, a review on the recent progress of SEC is presented and
      selected examples involving surface-enhanced Raman scattering (SERS), ultraviolet
      visible (UV-Vis), near-infrared (NIR), Fourier transform infrared (FTIR),
      fluorescence, as well as other SEC are summarized to fully demonstrate these
      techniques. In addition, the optically transparent electrodes and SEC cell
      design, and the typical applications of SEC in mechanism study, electrochromic
      device fabrication, sensing and protein study are fully introduced. Finally, the
      key issues, future perspectives and trends in the development of SEC are also
      discussed.

PMID- 29379917
TI  - Selective self-assembly and light emission tuning of layered hybrid perovskites
      on patterned graphene.
AB  - The emission of light in two-dimensional (2-D) layered hybrid organic lead halide
      perovskites, namely (R-NH3)2PbX4, can be effectively tuned using specific
      building blocks for the perovskite formation. Herein this behaviour is combined
      with a non-covalent graphene functionalization allowing excellent selectivity and
      spatial resolution of the perovskite film growth, promoting the formation of
      hybrid 2-D perovskite : graphene heterostructures with uniform coverage of up to
      centimeter scale graphene sheets and arbitrary shapes down to 5 MUm. Using cryo
      Raman microspectroscopy, highly resolved spectra of the perovskite phases were
      obtained and the Raman mapping served as a convenient spatially resolved
      technique for monitoring the distribution of the perovskite and graphene
      constituents on the substrate. In addition, the stability of the perovskite phase
      with respect to the thermal variation was inspected in situ by X-ray diffraction.
      Finally, time-resolved photoluminescence characterization demonstrated that the
      optical properties of the perovskite films grown on graphene are not hampered.
      Our study thus opens the door to smart fabrication routes for (opto)-electronic
      devices based on 2-D perovskites in contact with graphene with complex
      architectures.

PMID- 29379918
TI  - Nickel-catalyzed cross-coupling of aldehydes with aryl halides via hydrazone
      intermediates.
AB  - Traditional cross-couplings require stoichiometric organometallic reagents. A
      novel nickel-catalyzed cross-coupling reaction between aldehydes and aryl halides
      via hydrazone intermediates has been developed, merging the Wolff-Kishner
      reduction and the classical cross-coupling reactions. Aromatic aldehydes, aryl
      iodides and aryl bromides are especially effective in this new cross-coupling
      chemistry.

PMID- 29379919
TI  - A novel deep red-emitting phosphor KMgLaTeO6:Mn4+ with high thermal stability and
      quantum yield for w-LEDs: structure, site occupancy and photoluminescence
      properties.
AB  - In this work, a novel deep red-emitting phosphor KMgLaTeO6:Mn4+ potentially used
      in w-LEDs is reported, which can be efficiently excited with UV or blue light
      with a high quantum yield of 68.9% upon 365 nm excitation. More importantly, the
      luminescence thermal stability of this kind of phosphor shows excellent
      performance.

PMID- 29379920
TI  - A nano-catalytic approach for C-B bond formation reactions.
AB  - Herein, we present a chronological survey of the metal/metal oxide nanoparticle
      catalysed borylation reactions. Transition metal-catalysed borylation is
      considered to be one of the most efficient methods for the synthesis of
      organoboron derivatives. Considering chemical and pharmaceutical processes, the
      major drawbacks of homogeneous catalysis are metal contamination in products and
      inability to recover catalysts for reuse, which limit its application
      industrially, in biomolecules, and materials science. The use of nanoparticles as
      heterogeneous catalysts is a current topic of research to overcome these
      limitations. This review gives an overview of the metal nanoparticle-catalysed
      borylation reactions and also discusses the reaction mechanisms.

PMID- 29379921
TI  - Influence of a silver salt on the nanostructure of a Au(111)/ionic liquid
      interface: an atomic force microscopy study and theoretical concepts.
AB  - Ionic liquids (ILs) form a multilayered structure at the solid/electrolyte
      interface, and the addition of solutes can alter it. For this purpose, we have
      investigated the influence of the silver bis(trifluoromethylsulfonyl)amide
      (AgTFSA) concentration in 1-butyl-1-methylpyrrolidinium
      bis(trifluoromethylsulfonyl)amide ([Py1,4]TFSA) on the layering using in situ
      atomic force microscopy. AFM investigations revealed that the Au(111)/electrolyte
      interface indeed depends on the concentration of the salt where a typical " IL"
      multilayered structure is retained only at quite low concentrations of the silver
      salt (e.g. <=200 MUM). However, at 200 MUM AgTFSA/[Py1,4]TFSA and above this "IL"
      multilayered structure is disturbed/varied. A simple double layer structure was
      observed at 500 MUM AgTFSA in [Py1,4]TFSA. Furthermore, the widths of the
      innermost layers have been found to be dependent on the concentration and on the
      applied electrode potentials. Our AFM results show that the concentration of
      solutes strongly influences the structure of the electrode/electrolyte interface
      and can provide new insights into the electrical double layer structure of the
      electrode/ionic liquid interface. We also introduce a semi-continuum theory to
      discuss the double layer structure.

PMID- 29379922
TI  - The influence of the size and symmetry of cations and anions on the
      physicochemical behavior of organic ionic plastic crystal electrolytes mixed with
      sodium salts.
AB  - The phase behaviour, ionic conductivity, electrochemical stability and diffusion
      coefficients of mobile components in three organic ionic plastic crystals
      (OIPCs): triisobutylmethylphosphonium bis(fluorosulphonyl)amide (P1i444FSI),
      triisobutylmethylphosphonium bis(trifluromethanesulphonyl)amide (P1i444NTf2) and
      trimethylisobutylphosphonium bis(trifluoromethanesulphonyl)amide (P111i4NTf2) are
      compared to study the effect of the anions and cations on phase behaviour and
      dynamics. The FSI-based OIPC shows lower melting point and higher conductivity
      values most likely because of the higher degree of charge distributions and
      weaker ion-ion interactions compared to NTf2 anion-based OIPCs. Cyclic
      voltammetry of electrolytes consisting of these OIPCs with 70 mol% sodium salt
      incorporated indicates stable sodium plating/stripping behaviour at 70 and 50 
      degrees C for all samples. The magnitude of the peak currents, however, are much
      higher for the FSI-based electrolyte.

PMID- 29379923
TI  - Synthesis, isomerisation and biological properties of mononuclear ruthenium
      complexes containing the bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane ligand.
AB  - A series of mononuclear ruthenium(ii) complexes containing the tetradentate
      ligand bis[4(4'-methyl-2,2'-bipyridyl)]-1,7-heptane have been synthesised and
      their biological properties examined. In the synthesis of the [Ru(phen')(bb7)]2+
      complexes (where phen' = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyl- and
      3,4,7,8-tetramethyl- derivatives), both the symmetric cis-alpha and non-symmetric
      cis-beta isomers were formed. However, upon standing for a number of days (or
      more quickly under harsh conditions) the cis-beta isomer converted to the more
      thermodynamically stable cis-alpha isomer. The minimum inhibitory concentrations
      (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(ii)
      complexes were determined against six strains of bacteria: Gram-positive
      Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and
      the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and
      Pseudomonas aeruginosa (P. aeruginosa). The results showed that the [Ru(5
      NO2phen)(bb7)]2+ complex had little or no activity against any of the bacterial
      strains. By contrast, for the other cis-alpha-[Ru(phen')(bb7)]2+ complexes, the
      antimicrobial activity increased with the degree of methylation. In particular,
      the cis-alpha-[Ru(Me4phen)(bb7)]2+ complex showed excellent and uniform MIC
      activity against all bacteria. By contrast, the MBC values for the cis-alpha
      [Ru(Me4phen)(bb7)]2+ complex varied considerably across the bacteria and even
      within S. aureus and E. coli strains. In order to gain an understanding of the
      relative antimicrobial activities, the DNA-binding affinity, cellular
      accumulation and water-octanol partition coefficients (log P) of the ruthenium
      complexes were determined. Interestingly, all the [Ru(phen')(bb7)]2+ complexes
      exhibited stronger DNA binding affinity (Ka ~ 1 * 107 M-1) than the well-known
      DNA-intercalating complex [Ru(phen)2(dppz)]2+ (where dppz = dipyrido[3,2-a:2',3'
      c]phenazine).

PMID- 29379924
TI  - Oxidation behaviour of U3Si2: an experimental and first principles investigation.
AB  - Uranium-containing metallic systems such as U3Si2 are potential Accident Tolerant
      Fuels (ATFs) for Light Water Reactors (LWRs) and the next generation of nuclear
      reactors. Their oxidation behaviour, especially in oxygen and water-enriched
      environments, plays a critical role in determining their applicability in
      commercial reactors. In this work, we have investigated the oxidation behaviour
      of U3Si2 experimentally and by theoretical computation. The appearance of oxide
      signatures has been established from X-ray diffraction (XRD) and Raman
      spectroscopic techniques after oxidation of the solid U3Si2 sample in synthetic
      air (oxygen and nitrogen). We have also studied the changes in the electronic
      structure as well as the energetics of oxygen interactions on the U3Si2 surfaces
      using first principles calculations in the Density Functional Theory (DFT)
      formalism. The detailed charge transfer and bond length analyses revealed the
      preferential formation of mixed oxides of UO2 and SiO2 on the U3Si2{001} surface
      as well as UO2 alone on the U3Si2{110} and {111} surfaces. The formation of the
      peroxo (O22-) state confirmed the dissociation of molecular oxygen before U3Si2
      oxidation. Core experimental analyses of the oxidized U3Si2 samples have revealed
      the formation of higher oxides from Raman spectroscopy and XRD techniques. This
      work is introduced to further a better understanding of the oxidation of U-Si
      metallic fuel compounds.

PMID- 29379925
TI  - Posner molecules: from atomic structure to nuclear spins.
AB  - We investigate "Posner molecules", calcium phosphate clusters with chemical
      formula Ca9(PO4)6. Originally identified in hydroxyapatite, Posner molecules have
      also been observed as free-floating molecules in vitro. The formation and
      aggregation of Posner molecules have important implications for bone growth, and
      may also play a role in other biological processes such as the modulation of
      calcium and phosphate ion concentrations within the mitochondrial matrix. In this
      work, we use a first-principles computational methodology to study the structure
      of Posner molecules, their vibrational spectra, their interactions with other
      cations, and the process of pairwise bonding. Additionally, we show that the
      Posner molecule provides an ideal environment for the six constituent 31P nuclear
      spins to obtain very long spin coherence times. In vitro, the spins could provide
      a platform for liquid-state nuclear magnetic resonance quantum computation. In
      vivo, the spins may have medical imaging applications. The spins have also been
      suggested as "neural qubits" in a proposed mechanism for quantum processing in
      the brain.

PMID- 29379926
TI  - New archetypes in self-assembled Phe-Phe motif induced nanostructures from
      nucleoside conjugated-diphenylalanines.
AB  - During the last two decades, the molecular self-assembly of the short peptide
      diphenylalanine (Phe-Phe) motif has attracted increasing focus due to its unique
      morphological structure and utility for potential applications in biomaterial
      chemistry, sensors and bioelectronics. Due to the ease of their synthetic
      modifications and a plethora of available experimental tools, the self-assembly
      of free and protected diphenylalanine scaffolds (H-Phe-Phe-OH, Boc-Phe-Phe-OH and
      Boc-Phe-Phe-OMe) has unfurled interesting tubular, vesicular or fibrillar
      morphologies. Developing on this theme, here we attempt to examine the effect of
      structure and properties (hydrophobic and H-bonding) modifying the functional C
      terminus conjugated substituents on Boc-Phe-Phe on its self-assembly process. The
      consequent self-sorting due to H-bonding, van der Waals force and pi-pi
      interactions, generates monodisperse nano-vesicles from these peptides
      characterized via their SEM, HRTEM, AFM pictures and DLS experiments. The
      stability of these vesicles to different external stimuli such as pH and
      temperature, encapsulation of fluorescent probes inside the vesicles and their
      release by external trigger are reported. The results point to a new direction in
      the study and applications of the Phe-Phe motif to rationally engineer new
      functional nano-architectures.

PMID- 29379927
TI  - Full-dimensional quantum mechanics calculations for the spectroscopic
      characterization of the isomerization transition states of HOCO/DOCO systems.
AB  - Full-dimensional quantum mechanics calculations were performed to determine the
      vibrational energy levels of HOCO and DOCO based on an accurate potential energy
      surface. Almost all of the vibrational energy levels up to 3500 cm-1 from the
      vibrational ground state were assigned, and the calculated energy levels in this
      work are well in agreement with the reported results by Bowman. The corresponding
      full dimensional wavefunctions present some special features. When the energy
      level approaches the barrier height, the trans-HOCO and cis-HOCO states strongly
      couple through tunneling interactions, and the tunneling interaction and Fermi
      resonance were observed in the DOCO system. The energy level patterns of trans
      HOCO, cis-HOCO and trans-DOCO provide a reasonable fitted barrier height using
      the fitting formula of Field et al., however, a discrepancy exists for the cis
      DOCO species which is considered as a random event. Our full-dimensional
      calculations give positive evidence for the accuracy of the spectroscopic
      characterization model of the isomerization transition state reported by Field et
      al., which was developed from one-dimensional model systems. Furthermore, the
      special case of cis-DOCO in this work means that the isotopic substitution can
      solve the problem of the accidental failure of Field's spectroscopic
      characterization model.

PMID- 29379928
TI  - Synthesis and characterization of heteroleptic titanium MOCVD precursors for TiO2
      thin films.
AB  - Heteroleptic titanium alkoxides with three different ligands, i.e.,
      [Ti(OiPr)(X)(Y)] (X = tridentate, Y = bidentate ligands), were synthesized to
      find efficient metal organic chemical vapor deposition (MOCVD) precursors for
      TiO2 thin films. Acetylacetone (acacH) or 2,2,6,6-tetramethyl-3,5-heptanedione
      (thdH) was employed as a bidentate ligand, while N-methyldiethanolamine (MDEA)
      was employed as a tridentate ligand. It was expected that the oxygen and moisture
      susceptibility of titanium alkoxides, as well as their tendency to form
      oligomers, would be greatly reduced by placing multidentate and bulky ligands
      around the center Ti atom. The synthesized heteroleptic titanium alkoxides were
      characterized both physicochemically and crystallographically, and their thermal
      behaviors were also investigated. [Ti(OiPr)(MDEA)(thd)] was found to be monomeric
      and stable against moisture; it also showed good volatility in the temperature
      window between volatilization and decomposition. This material was used as a
      single-source precursor during MOCVD to generate TiO2 thin films on silicon
      wafers. The high thermal stability of [Ti(OiPr)(MDEA)(thd)] enabled the
      fabrication of TiO2 films over a wide temperature range, with steady growth rates
      between 500 and 800  degrees C.

PMID- 29379929
TI  - Dissipative disassembly of colloidal microgel crystals driven by a coupled cyclic
      reaction network.
AB  - A plethora of natural systems rely on the consumption of chemical fuel or input
      of external energy to control the assembly and disassembly of functional
      structures on demand. While dissipative assembly has been demonstrated, the
      control of structural breakdown using a dissipative cycle remains almost
      unexplored. Here, we propose and realize a dissipative disassembly process using
      two coupled cyclic reactions, in which protons mediate the interaction between
      the cycles. We show how an ordered colloidal crystal, can cyclically transform
      into a disordered state by addition of energy to a chemical cycle, reversibly
      activating a photoacid. This cycle is coupled to the colloidal assembly cycle via
      the exchange of protons, which in turn trigger charging of the particles. This
      system is an experimental realization of a cyclic reaction-assembly network and
      its principle can be extended to other types of structure formation.

PMID- 29379930
TI  - Rapid construction of substituted 3-amino-1,5-benzothiazepin-4(5H)-one dipeptide
      scaffolds through an Ugi-4CR - Ullmann cross-coupling sequence.
AB  - A 3-step methodology for the synthesis of 1,5-benzothiazepin-4(5H)-one
      dipeptidomimetics has been elaborated via an Ugi-4CR followed by a S-trityl
      deprotection and an intramolecular Cu(i)-catalyzed Ullmann condensation with
      moderate to good yields. In silico and NMR conformational studies showed that the
      lowest energy conformers stabilize gamma- and beta-turn structures.

PMID- 29379931
TI  - A non-tight chemomechanical coupling model for force-dependence of movement
      dynamics of molecular motors.
AB  - Based on the available experimental evidence, we present a simple and general
      model to describe the movement dynamics of molecular motors that can move
      processively on their linear tracks by using the chemical energy derived from ATP
      hydrolysis. An important aspect of the model is the non-tight coupling between
      the ATP hydrolysis and mechanical stepping, in contrast to the prevailing models
      presented in the literature that assume the tight chemomechanical coupling. With
      kinesin as an example, based on the current model, we study in detail its
      movement dynamics under a backward load, reproducing well the diverse available
      single-molecule experimental data such as the forward to backward step ratio,
      velocity, dwell time, randomness, run length, etc., versus the load. Moreover,
      predicted results are provided on the force-dependence of the mean number of ATP
      molecules consumed per mechanical step. Additionally, the theoretical data for
      the dynamics of myosin-V obtained based on the model are also in good agreement
      with the available experimental data.

PMID- 29379932
TI  - Two-photon spectroscopy of the NaLi triplet ground state.
AB  - We employ two-photon spectroscopy to study the vibrational states of the triplet
      ground state potential (a3Sigma+) of the 23Na6Li molecule. Pairs of Na and Li
      atoms in an ultracold mixture are photoassociated into an excited triplet
      molecular state, which in turn is coupled to vibrational states of the triplet
      ground potential. Vibrational state binding energies, line strengths, and
      potential fitting parameters for the triplet ground a3Sigma+ potential are
      reported. We also observe rotational splitting in the lowest vibrational state.

PMID- 29379933
TI  - Correction: General optimization procedure towards the design of a new family of
      minimal parameter spin-component-scaled double-hybrid density functional theory.
AB  - Correction for 'General optimization procedure towards the design of a new family
      of minimal parameter spin-component-scaled double-hybrid density functional
      theory' by Loic M. Roch and Kim K. Baldridge, Phys. Chem. Chem. Phys., 2017, 19,
      26191-26200.

PMID- 29379934
TI  - Evidence of electrostatic-enhanced depletion attraction in the structural
      properties and phase behavior of binary charged colloidal suspensions.
AB  - In this paper we study the structure and phase behavior of binary mixtures of
      charged particles at low ionic strength. Due to the large size asymmetry between
      both species, light scattering measurements give us access only to the partial
      static structure factor that corresponds to the big particles. We observe that
      the addition of small charged colloids produces a decrease of the main peak of
      the measured static structure factor and a shift to larger scattering vector
      values. This finding is in agreement with theory based on integral equations with
      the Hypernetted-Chain Closure (HNC) relation. The effective interaction between
      two big particles due to the presence of small particles is obtained by a HNC
      inversion scheme and used in numerical simulations that adequately reproduce the
      experiments. We find that the presence of small particles induces an
      electrostatic depletion screening among the big colloids, creating around them an
      exclusion zone for the small charged colloids greater than that caused in the
      case of neutral small colloids, which in turn augments the depletion effect.

PMID- 29379935
TI  - Correction: Cationic phthalocyanine dendrimers as potential antimicrobial
      photosensitisers.
AB  - Correction for 'Cationic phthalocyanine dendrimers as potential antimicrobial
      photosensitisers' by Ruben Ruiz-Gonzalez et al., Org. Biomol. Chem., 2017, 15,
      9008-9017.

PMID- 29379936
TI  - Thermal activation of methane by vanadium boride cluster cations VBn+ (n = 3-6).
AB  - Investigation on the reactivity of atomic clusters represents an important
      approach to discover new species to activate and transform methane, the most
      stable alkane molecule. While a few types of transition metal species have been
      found to be capable of cleaving the C-H bond of methane, methane activation by
      the transition metal boride species has not been explored yet. This study reports
      that vanadium boride cluster cations VBn+ (n = 3-6) can dehydrogenate methane
      under thermal collision conditions. The mechanistic details of the efficient
      reactions have been elucidated by quantum chemistry calculations on the VB3+
      reaction system. Compared to the non-polar bare B3 cluster, the B3 moiety in VB3+
      can be polarized by the V+ cation and thus its reactivity toward methane can be
      much enhanced. This study provides new insights into the rational design of boron
      based catalysts for methane activation.

PMID- 29379937
TI  - Buried treasure: biosynthesis, structures and applications of cyclic peptides
      hidden in seed storage albumins.
AB  - Covering: 1999 up to the end of 2017The small cyclic peptide SunFlower Trypsin
      Inhibitor-1 (SFTI-1) from sunflower seeds is the prototypic member of a novel
      family of natural products. The biosynthesis of these peptides is intriguing as
      their gene-encoded peptide backbone emerges from a precursor protein that also
      contains a seed storage albumin. The peptide sequence is cleaved out from the
      precursor and cyclised by the albumin-maturing enzymatic machinery. Three
      dimensional solution NMR structures of a number of these peptides, and of the
      intact precursor protein preproalbumin with SFTI-1, have now been elucidated.
      Furthermore, the evolution of the family has been described and a detailed
      understanding of the biosynthetic steps, which are necessary to produce cyclic
      SFTI-1, is emerging. Macrocyclisation provides peptide stability and thus
      represents a key strategy in peptide drug development. Consequently the
      constrained structure of SFTI-1 has been explored as a template for protein
      engineering, for tuning selectivity towards clinically relevant proteases and for
      grafting in sequences with completely novel functions. Here we review the
      discovery of the SFTI-1 peptide family, their evolution, biosynthetic origin, and
      structural features, as well as highlight the potential applications of this
      unique class of natural products.

PMID- 29379938
TI  - Epidermal growth factor and transforming growth factor-alpha in human milk of
      different lactation stages and different regions and their relationship with
      maternal diet.
AB  - Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha)
      are important growth-promoting factors in human milk and play an important role
      in a newborn's gastrointestinal function. The aim of the present study was to
      compare EGF and TGF-alpha contents in breast milk from different lactation
      periods and different regions and further analyze the effect of maternal diet on
      the concentration of EGF and TGF-alpha in breast milk. Breast milk samples and 24
      hour food records were obtained from lactating mothers on day 1 (colostrum), day
      14 (transitional milk) and day 42 (mature milk) from Hangzhou (n = 76), Lanzhou
      (n = 76) and Beijing (n = 76), China. EGF and TGF-alpha levels were determined by
      enzyme-linked immunosorbent assay (ELISA). The concentration of EGF in breast
      milk decreased over lactation periods (p < 0.001) while the TGF-alpha content in
      breast milk increased over lactation periods (p < 0.001). During all of the three
      lactation periods, the EGF content in the breast milk from Lanzhou participants
      was significantly higher than Beijing and Hangzhou participants (p < 0.001),
      while the TGF-alpha content in the breast milk from Beijing was significantly
      higher than that from Lanzhou and Hangzhou (p < 0.001). The concentration of EGF
      in breast milk decreased with the increasing intake of proteins (p = 0.042),
      total energy (p = 0.031), vegetables (p = 0.002), fruits (p < 0.001), soy
      products (p = 0.001) and dairy foods (p < 0.001), while the TGF-alpha content in
      breast milk increased with the increasing intake of carbohydrates (p = 0.023) and
      dairy products (p = 0.011) and decreased with the increasing intake of proteins
      (p = 0.008) and meat (p = 0.016). The EGF and TGF-alpha contents in breast milk
      were greatly influenced by regions and lactation periods and there was also a
      strong relationship with maternal diet.

PMID- 29379939
TI  - Hand-powered centrifugal microfluidic platform inspired by the spinning top for
      sample-to-answer diagnostics of nucleic acids.
AB  - Point-of-care (POC), sample-to-answer and electricity-free nucleic acid
      diagnostic tools are vital for health care and disease control in resource
      limited settings where centralized medical facilities or even electric power may
      remain unreliable. Inspired by one of the oldest recognizable toys, the spinning
      top, here we report a fully hand-powered centrifugal microfluidic platform for
      the diagnostics of pathogenic bacteria. Assay procedures such as zeolite-based
      purification of nucleic acids, loop-mediated isothermal amplification (LAMP) and
      visual detection of fluorescence signals are integrated into a single
      microfluidic disc. A simple pull-out operation of the top rack of the customized
      centrifuge initiates high-speed rotation of the disc, resulting in efficient
      actuation and mixing of preloaded sample/reagent fluids. This microfluidic
      platform enables the simultaneous detection of six kinds of pathogenic bacteria
      within a small disc in an electricity-free manner, showing great promise in
      sample-to-answer nucleic acid detection in remote settings.

PMID- 29379941
TI  - Ce(iii)-catalyzed highly efficient synthesis of pyridyl benzamides from
      aminopyridines and nitroolefins without external oxidants.
AB  - An efficient synthesis of a variety of pyridyl benzamides from 2-aminopyridines
      and nitroolefins is described. This rare-earth-metal-catalyzed reaction provides
      the corresponding products with broad substrate scope in moderate to excellent
      yields, in the absence of additives and external oxidants. Water is used as the
      source of the carbonyl oxygen atom in pyridyl benzamides. Furthermore, 2
      substituted oxazolo[4,5-b]pyridines are formed in good yields under the standard
      conditions when 2-aminopyridin-3-ols are used as the substrates.

PMID- 29379940
TI  - gem-Diborylalkanes: recent advances in their preparation, transformation and
      application.
AB  - Recently, gem-diborylalkanes have attracted much attention as versatile building
      blocks and fundamental intermediates in organic synthesis, because they enable
      multiple C-C bond construction and further transformation at C-B bonds.
      Importantly, gem-diborylalkanes can be utilised as bisnucleophilic partners in a
      variety of chemo-selective C-C bond-forming reactions. This review describes
      recent developments in synthesising gem-diborylalkanes in complex molecules along
      with their chemical transformation. In the first part of the review the different
      synthetic approaches used to synthesise gem-diborylalkanes are described. In the
      second part, an overview of the chemoselective transformation of gem
      diborylalkanes into various functionalized materials is discussed along with one
      carbon homologation of diborylmethane via a selective uni- and bidirectional
      method.

PMID- 29379942
TI  - An Unusual Amnestic Syndrome Associated With Combined Fentanyl and Cocaine Use.

PMID- 29379944
TI  - Appearance of an Unusual Cerebellar Lesion.

PMID- 29379945
TI  - Preschool and Early Education Experiences.

PMID- 29379943
TI  - Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy: A
      Randomized Clinical Trial.
AB  - Importance: Management of painful diabetic peripheral neuropathy remains
      challenging. Most therapies provide symptomatic relief with varying degrees of
      efficacy. Tocotrienols have modulatory effects on the neuropathy pathway and may
      reduce neuropathic symptoms with their antioxidative and anti-inflammatory
      activities. Objective: To evaluate the efficacy of oral mixed tocotrienols for
      patients with diabetic peripheral neuropathy. Design, Setting, and Participants:
      The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind,
      placebo-controlled trial that recruited participants from January 30, 2011, to
      December 7, 2014, with 12 months of follow-up. This trial screened 14 289
      patients with diabetes from 6 health clinics and ambulatory care units from 5
      public hospitals in Malaysia. A total of 391 patients who reported neuropathic
      symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy
      Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and
      an NIS of 2 or higher were recruited. Interventions: Patients were randomized to
      receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12
      months. Patients with hyperhomocysteinemia (homocysteine level >=2.03 mg/L)
      received oral folic acid, 5 mg once daily, and methylcobalamin, 500 MUg thrice
      daily, in both groups. Main Outcomes and Measures: The primary outcome was
      patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and
      asleep numbness) changes at 12 months. The secondary outcomes were NIS and
      sensory nerve conduction test result. Results: Of 391 eligible patients, 300 were
      recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration
      of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS
      changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, 
      1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95%
      CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were
      found between both groups. In post hoc subgroup analyses, tocotrienols reduced
      lancinating pain among patients with hemoglobin A1C levels greater than 8% (P =
      .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1
      year. Serious adverse events in both groups were similar, except more infections
      were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported
      were of modified intention-to-treat analyses. Conclusions and Relevance:
      Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve
      overall neuropathic symptoms. The preliminary observations on lancinating pain
      among subsets of patients require further exploration. Trial Registration:
      National Medical Research Registry Identifier: NMRR-10-948-7327 and
      clinicaltrials.gov Identifier: NCT01973400.

PMID- 29379946
TI  - Lateral Displacement of the Inner Canthi in a Child of Deaf Parents.

PMID- 29379947
TI  - Outcomes of Follow-up Visits After Bronchiolitis Hospitalizations.

PMID- 29379948
TI  - Mid- and Long-Term Health Risks in Living Kidney Donors: A Systematic Review and
      Meta-analysis.
AB  - Background: Long-term health risks for adults who donate kidneys are unclear.
      Purpose: To summarize evidence about mid- and long-term health risks associated
      with living kidney donation in adults. Data Sources: PubMed, Embase, Scopus, and
      PsycINFO without language restriction from April 1964 to July 2017. Study
      Selection: Observational studies with at least 1 year of follow-up that compared
      health outcomes in adult living kidney donors versus nondonor populations. Data
      Extraction: Two investigators independently extracted study data and assessed
      study quality. Data Synthesis: 52 studies, comprising 118 426 living kidney
      donors and 117 656 nondonors, were included. Average follow-up was 1 to 24 years.
      No evidence suggested higher risk for all-cause mortality, cardiovascular
      disease, hypertension, type 2 diabetes, or adverse psychosocial health outcomes
      in living kidney donors than in nondonor populations. Donors had higher diastolic
      blood pressure, lower estimated glomerular filtration rates, and higher risk for
      end-stage renal disease (ESRD) (relative risk [RR], 8.83 [95% CI, 1.02 to 20.93])
      and preeclampsia in female donors (RR, 2.12 [CI, 1.06 to 4.27]). Despite the
      increased RR, donors had low absolute risk for ESRD (incidence rate, 0.5 event
      [CI, 0.1 to 4.9 events] per 1000 person-years) and preeclampsia (incidence rate,
      5.9 events [CI, 2.9 to 8.9 events] per 100 pregnancies). Limitation:
      Generalizability was limited by selected control populations, few studies
      reported pregnancy-related outcomes, and few studies were from low- and middle
      income countries. Conclusion: Although living kidney donation is associated with
      higher RRs for ESRD and preeclampsia, the absolute risk for these outcomes
      remains low. Compared with nondonor populations, living kidney donors have no
      increased risk for other major chronic diseases, such as type 2 diabetes, or for
      adverse psychosocial outcomes. Primary Funding Source: National Health Service
      Blood and Transplant and National Institute for Health Research. (PROSPERO:
      CRD42017072284).

PMID- 29379949
TI  - A Case of Possible Pacemaker Malfunction: The Pacemaker That Did Not Make Sense.

PMID- 29379950
TI  - Proportion of Decedents' Expenditures Among Recent Reductions in Medicare
      Expenditures.

PMID- 29379951
TI  - India's Call to Action-Prioritize Chronic Cardiovascular Disease.

PMID- 29379952
TI  - Acute Brain Lesions on Magnetic Resonance Imaging and Delayed Neurological
      Sequelae in Carbon Monoxide Poisoning.
AB  - Importance: Preventing delayed neurological sequelae is a major goal of treating
      acute carbon monoxide poisoning, but to our knowledge there are no reliable tools
      for assessing the probability of these sequelae. Objectives: To determine whether
      acute brain lesions on diffusion-weighted imaging are related to subsequent
      development of delayed neurological sequelae after acute carbon monoxide
      poisoning. Design, Setting, and Participants: This registry-based observational
      study was conducted at a university hospital in Seoul, Korea, between April 1,
      2011, and December 31, 2015. Of 700 patients (aged >=18 years) with acute carbon
      monoxide poisoning, 433 patients (61.9%) who underwent diffusion-weighted imaging
      at an emergency department were considered for the study. Patients who developed
      cardiac arrest before diffusion-weighted imaging (n = 3), had persistent
      neurological symptoms at discharge (n = 8), committed suicide soon after
      discharge (n = 1), and were lost to follow-up (n = 34) were excluded. Exposure:
      The presence of unambiguous, high-signal-intensity, acute brain lesions on
      diffusion-weighted imaging (b = 1000 s/mm2). Main Outcomes and Measures:
      Development of delayed neurological sequelae defined as any neurological symptoms
      or signs that newly developed within 6 weeks of discharge. Results: Of the 387
      included patients (143 women [37.0%]; median age, 42.0 years [interquartile
      range, 32.0-56.0 years]), acute brain lesions on diffusion-weighted imaging were
      observed in 104 patients (26.9%). Among these, 77 patients (19.9%) had globus
      pallidus lesions, 13 (3.4%) had diffuse lesions, and 57 (14.7%) had focal lesions
      (37 patients [9.6%] had >1 pattern concurrently). Lesions were supratentorial and
      infratentorial in 101 and 23 patients, respectively. Delayed neurological
      sequelae occurred in 101 patients (26.1%). Multivariable logistic regression
      analysis indicated that the presence of acute brain lesions was independently
      associated with development of delayed neurological sequelae (adjusted odds
      ratio, 13.93; 95% CI, 7.16-27.11; P < .001). The sensitivity and specificity of
      acute brain lesions to assess the probability of delayed neurological sequelae
      were 75.2% (95% CI, 66.8%-83.7%) and 90.2% (95% CI, 86.8%-93.7%), respectively.
      In addition, the positive and negative predictive values were 73.1% (95% CI,
      64.6%-81.6%) and 91.2% (95% CI, 87.9%-94.5%), respectively. Conclusions and
      Relevance: The presence of acute brain lesions was significantly associated with
      the development of delayed neurological sequelae. Diffusion-weighted imaging
      during the acute phase of carbon monoxide poisoning may therefore help identify
      patients at risk of developing these debilitating sequelae.

PMID- 29379954
TI  - Principles for a Framework for Alternative Payment Models.

PMID- 29379953
TI  - Effect of an In-Hospital Multifaceted Clinical Pharmacist Intervention on the
      Risk of Readmission: A Randomized Clinical Trial.
AB  - Importance: Hospital readmissions are common among patients receiving multiple
      medications, with considerable costs to the patients and society. Objective: To
      determine whether a multifaceted pharmacist intervention based on medication
      review, patient interview, and follow-up can reduce the number of readmissions
      and emergency department (ED) visits. Design, Setting, and Participants: This
      randomized clinical multicenter study (Odense Pharmacist Trial Investigating
      Medication Interventions at Sector Transfer [OPTIMIST]) enrolled patients from
      September 1, 2013, through April 23, 2015, with a follow-up of 6 months completed
      on October 31, 2015. Consecutive medical patients in an acute admission ward who
      were 18 years or older and who used 5 or more medications were invited to
      participate. Of 1873 patients invited to participate, 1499 (80.0%) accepted. The
      medication review and patient interview were conducted in the hospital and
      followed up in collaboration with primary care. Analysis was based on intention
      to treat. Interventions: The patients were randomized into 3 groups receiving
      usual care (no intervention), a basic intervention (medication review), and an
      extended intervention (medication review, 3 motivational interviews, and follow
      up with the primary care physician, pharmacy, and nursing home). Main Outcomes
      and Measures: The prespecified primary outcomes were readmission within 30 or 180
      days and ED visits within 180 days. The primary composite end point was
      readmission or an ED visit within 180 days. Secondary outcomes were drug-related
      readmissions within 30 and 180 days after inclusion, and all-cause mortality and
      drug-related mortality. Results: A total of 1467 patients (679 men [46.3%] and
      788 women [53.7%]; median age, 72 years; interquartile range, 63-80 years) were
      part of the primary analysis, including 498 randomized to usual care, 493
      randomized to the basic intervention, and 476 randomized to the extended
      intervention. The extended intervention had a significant effect on the numbers
      of patients who were readmitted within 30 days (hazard ratio [HR], 0.62; 95% CI,
      0.46-0.84) or within 180 days (HR, 0.75; 95% CI, 0.62-0.90) after inclusion and
      on the number of patients who experienced the primary composite end point (HR,
      0.77; 95% CI, 0.64-0.93). The study showed a nonsignificant reduction in drug
      related readmissions within 30 days (HR, 0.65; 95% CI, 0.39-1.09) and within 180
      days (HR, 0.80; 95% CI, 0.59-1.08) after inclusion and in deaths (HR, 0.83; 95%
      CI, 0.22-3.11). The number needed to treat to achieve the primary composite
      outcome for the extended intervention (vs usual care) was 12. Conclusions and
      Relevance: A multifaceted clinical pharmacist intervention may reduce the number
      of ED visits and hospital readmissions. Trial Registration: clinicaltrials.gov
      Identifier: NCT03079375.

PMID- 29379956
TI  - Smart Hospital Discharges to Address a Neglected Epidemic in Sepsis in Low- and
      Middle-Income Countries.

PMID- 29379955
TI  - A Multicomponent, Preschool to Third Grade Preventive Intervention and
      Educational Attainment at 35 Years of Age.
AB  - Importance: Educational attainment is the leading social determinant of health,
      but few studies of prevention programs have examined whether the programs are
      associated with educational attainment outcomes after the mid-20s, especially for
      large-scale programs that provide a longer duration of services. Objective: To
      examine the association between a preschool to third grade intervention and
      educational attainment at midlife and differences by program duration, sex, and
      parental educational level. Design, Setting, and Participants: This matched
      group, alternative intervention study assessed 1539 low-income minority children
      born in 1979 or 1980 who grew up in high-poverty neighborhoods in Chicago,
      Illinois. The comparison group included 550 children primarily from randomly
      selected schools participating in the usual early intervention. A total of 989
      children who entered preschool in 1983 or 1984 and completed kindergarten in 1986
      were included in the Chicago Longitudinal Study and were followed up for 27 to 30
      years after the end of a multicomponent intervention. A total of 1398
      participants (90.8%) in the original sample had educational attainment records at
      35 years of age. The study was performed from January 1, 2002, through May 31,
      2015. Interventions: The Child-Parent Center Program provides school-based
      educational enrichment and comprehensive family services from preschool to third
      grade (ages 3-9 years). Main Outcomes and Measures: Educational outcomes from
      administrative records and self-report included school dropout, 4-year high
      school graduation, years of education, postsecondary credential, and earned
      degrees from associate's to master's or higher. Results: A total of 1539
      participants (mean [SD] age, 35.1 [0.32] years; 1423 [92.9%] black and 108 [7.1%]
      Hispanic) were included in the study. After weighting on 2 propensity scores,
      preschool participants had higher rates of postsecondary degree completion,
      including associate's degree or higher (15.7% vs 10.7%; difference, 5.0%; 95% CI,
      1.0%-9.0%), master's degree (4.2% vs 1.5%; difference, 2.7%; 95% CI, 1.3%-4.1%),
      and years of education (12.81 vs 12.32; difference, 0.49; 95% CI, 0.20-0.77).
      Duration of participation showed a consistent linear association with outcomes.
      Compared with fewer years, preschool to second or third grade participation led
      to higher rates of associate's degree or higher (18.5% vs 12.5%; difference,
      6.0%; 95% CI, 1.0%-11.0%), bachelor's degree (14.3% vs 8.2%; difference, 6.1%;
      95% CI, 1.3%-10.9%), and master's degree or higher (5.9% vs 2.3%; difference,
      3.6%; 95% CI, 1.4%-5.9%). The pattern of benefits was robust and favored male
      participants for high school graduation, female participants for college
      attainment, and those from lower-educated households. Conclusions and Relevance:
      This study indicates that an established early and continuing intervention is
      associated with higher midlife postsecondary attainment. Replication and
      extension of findings to other locations and populations should further
      strengthen confidence in the health benefits of large-scale preventive
      interventions.

PMID- 29379957
TI  - Self-Stigma and Age-Related Hearing Loss: A Qualitative Study of Stigma Formation
      and Dimensions.
AB  - Purpose: This study explored experiences of self-stigma among older persons with
      age-related hearing loss (ARHL) using Corrigan's conceptualization of self-stigma
      process formation and the attribution model as its theoretical framework. Method:
      In-depth semistructured interviews were conducted with 11 older persons (mean age
      = 81 years) with ARHL. Results: Self-stigma was present in the lives of the
      participants. Analysis revealed the existence of 3 stages of self-stigma in which
      the 3 core dimensions of stigma (cognitive attributions: being old, stupid, and
      crippled; emotional reactions: shame, pity, and feeling ridiculed; and behavioral
      reactions: concealment, distancing, and adapting to hearing aids) were observed.
      Hearing devices emerged as having a significant influence on stigmatic
      experiences in all stages and dimensions of self-stigma. Conclusion: The study
      contributes to the theoretical and practical understanding of self-stigma
      regarding ARHL as well as to the understanding of the role of hearing devices in
      the development of this stigma.

PMID- 29379958
TI  - Does Medicine Overemphasize IQ?

PMID- 29379959
TI  - Prevalence of Pulmonary Embolism in Patients With Syncope.
AB  - Importance: Sparse data and conflicting evidence exist on the prevalence of
      pulmonary embolism (PE) in patients with syncope. Objective: To estimate the
      prevalence of PE among patients presenting to the emergency department (ED) for
      evaluation of syncope. Design, Setting, and Participants: This retrospective,
      observational study analyzed longitudinal administrative data from 5 databases in
      4 different countries (Canada, Denmark, Italy, and the United States). Data from
      all adult patients (aged >=18 years) who presented to the ED were screened to
      identify those with syncope codes at discharge. Data were collected from January
      1, 2000, through September 30, 2016. Main Outcomes and Measures: The prevalence
      of PE at ED and hospital discharge, identified using codes from the International
      Classification of Diseases, was considered the primary outcome. Two sensitivity
      analyses considering prevalence of PE at 90 days of follow-up and prevalence of
      venous thromboembolism were performed. Results: A total of 1 671 944 unselected
      adults who presented to the ED for syncope were included. The prevalence of PE,
      according to administrative data, ranged from 0.06% (95% CI, 0.05%-0.06%) to
      0.55% (95% CI, 0.50%-0.61%) for all patients and from 0.15% (95% CI, 0.14%-0.16%)
      to 2.10% (95% CI, 1.84%-2.39%) for hospitalized patients. The prevalence of PE at
      90 days of follow-up ranged from 0.14% (95% CI, 0.13%-0.14%) to 0.83% (95% CI,
      0.80%-0.86%) for all patients and from 0.35% (95% CI, 0.34%-0.37%) to 2.63% (95%
      CI, 2.34%-2.95%) for hospitalized patients. Finally, the prevalence of venous
      thromboembolism at 90 days ranged from 0.30% (95% CI, 0.29%-0.31%) to 1.37% (95%
      CI, 1.33%-1.41%) for all patients and from 0.75% (95% CI, 0.73%-0.78%) to 3.86%
      (95% CI, 3.51%-4.24%) for hospitalized patients. Conclusions and Relevance:
      Pulmonary embolism was rarely identified in patients with syncope. Although PE
      should be considered in every patient, not all patients should undergo evaluation
      for PE.

PMID- 29379960
TI  - The Quest to Define Individual Risk After Living Kidney Donation.

PMID- 29379961
TI  - Review of the Neurological Implications of von Hippel-Lindau Disease.
AB  - Importance: von Hippel-Lindau (VHL) disease-associated central nervous system
      (CNS) lesions include hemangioblastomas and endolymphatic sac tumors (ELSTs),
      which are associated with significant neurological morbidity and mortality.
      Recent studies provide critical new biological, diagnostic, and management
      insights into these tumors. Observations: Biological features, natural history,
      clinical findings, and management strategies of VHL disease-associated CNS tumors
      are reviewed. The VHL disease results from a germline mutation of the VHL gene
      (located on the short arm of chromosome 3), a tumor suppressor that encodes for
      the VHL protein. Whereas VHL disease is associated with visceral manifestations,
      CNS lesions are the most common source of morbidity and mortality. Craniospinal
      hemangioblastomas are almost entirely (99%) found in the cerebellum, brainstem,
      and spinal cord. These tumors arise from multipotent hemangioblasts. Peritumoral
      cysts frequently underlie the clinical findings associated with hemangioblastomas
      (>90% of symptomatic tumors). Prospective natural history studies demonstrate
      that CNS hemangioblastomas typically grow in a saltatory pattern. Due to this
      unpredictable growth pattern, surgical resection is reserved for symptomatic
      lesions, as many tumors do not become symptomatic. Recent studies indicate that
      VHL disease-associated ELSTs cause audiovestibular morbidity (hearing loss,
      tinnitus, and vertigo) via 3 mechanisms-otic capsule invasion, intralabyrinthine
      hemorrhage, and endolymphatic hydrops. Specialized magnetic resonance imaging
      techniques have been defined to elucidate each of these mechanisms, even when a
      tumor mass is not identified on imaging. Endolymphatic sac tumors cause
      audiovestibular morbidity unrelated to size or progression, and resection is now
      recommended at initial discovery of a tumor mass or a tumor-associated mechanism
      of morbidity. Conclusions and Relevance: New insights into the development,
      pathobiological origin, natural history, and long-term outcomes of VHL disease
      associated CNS tumors have redefined their management and treatment indications
      and potentially provide new targeted therapeutic strategies. Resection is
      reserved for symptomatic hemangioblastomas, but early resection of newly detected
      ELSTs is now recommended.

PMID- 29379962
TI  - Provider Types and Outcomes in Obstructive Sleep Apnea Case Finding and
      Treatment: A Systematic Review.
AB  - Background: Obstructive sleep apnea (OSA) diagnosis and care models rely on sleep
      specialist physicians (SSPs) and can be expensive and inefficient. Purpose: To
      assess OSA case-finding accuracy and comparative effectiveness of care by non
      sleep specialists (NSSs) and SSPs. Data Sources: MEDLINE and CINAHL from January
      2000 through July 2017. Study Selection: English-language trials or observational
      studies comparing case finding or care by SSPs versus providers not specifically
      trained as SSPs (NSSs) for adults with suspected or diagnosed OSA. Data
      Extraction: One investigator extracted data and assessed risk of bias and
      strength of evidence, with confirmation by a second investigator. Primary
      outcomes were patient-centered (mortality, access to care, quality of life,
      patient satisfaction, adherence, symptom scores, and adverse events).
      Intermediate outcomes included resource use, costs, time to initiation of
      treatment, and case finding. Data Synthesis: Four observational studies (n = 580;
      mean age, 52 years; 77% male) reported good agreement between NSSs and SSPs on
      appropriate diagnostic testing and classification of OSA severity (low-strength
      evidence). Five randomized trials and 3 observational studies (n = 1515; mean
      age, 52 years; 68% male) found that care provided by NSSs and SSPs resulted in
      similar quality of life, adherence, and symptom scores (low-strength evidence).
      Evidence was insufficient for access to care and adverse events. Limitations:
      Many outcomes were reported infrequently or not at all. Many NSSs had extensive
      training or experience in sleep medicine, which limits generalizability of
      findings to providers with less experience. Conclusion: Care by NSSs and SSPs
      resulted in similar outcomes in adults with known or suspected OSA. Studies are
      needed to determine care model implementation and reproducibility of results in
      nonacademic settings and among less experienced NSSs. Primary Funding Source:
      Department of Veterans Affairs, Veterans Health Administration, Office of
      Research and Development, Quality Enhancement Research Initiative. (PROSPERO:
      CRD42016036810 [full Veterans Affairs Evidence-based Synthesis Program report]).

PMID- 29379965
TI  - Association Between Undergraduate Performance Predictors and Academic and
      Clinical Performance of Osteopathic Medical Students.
AB  - Context: Medical schools use a variety of preadmission indices to select
      potential students. These indices generally include undergraduate grade point
      average (GPA), Medical College Admission Test (MCAT) scores, and preadmission
      interviews. Objective: To investigate whether the admission indices used by
      Midwestern University Arizona College of Osteopathic Medicine are associated with
      the academic and clinical performance of their students. Methods: Associations
      between the prematriculation variables of undergraduate science GPA,
      undergraduate total GPA, MCAT component scores, and interview scores and the
      academic and clinical variables of the first- and second-year medical school GPA,
      Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) Level 1
      and Level 2-Cognitive Evaluation (CE) total and discipline scores, scores in
      clinical rotations for osteopathic competencies, COMLEX-USA Level 2-Performance
      Evaluation passage, and match status were evaluated. Two-tailed Pearson product
      moment correlations with a Bonferroni adjustment were used to examine these
      relationships. Results: The traditional predictors of science and total
      undergraduate GPA as well as total and component MCAT scores had small to
      moderate associations with first- and second-year GPA, as well as COMLEX-USA
      Level 1 and Level 2-CE total scores. Of all predictors, only the MCAT biological
      sciences score had a statistically significant correlation with failure of the
      COMLEX-USA Level 2-Performance Evaluation examination (P=.009). Average interview
      scores were associated only with the osteopathic competency of medical knowledge
      (r=0.233; n=209; P=.001), as assessed by clerkship preceptors. No predictors were
      associated with scores in objective structured clinical encounters or with
      failing to match to a residency position. Conclusion: The data indicate that
      traditional predictors of academic performance (undergraduate GPA, undergraduate
      science GPA, and MCAT scores) have small to moderate association with medical
      school grades and performance on COMLEX-USA Level 1 and Level 2-CE. This finding
      requires additional research into the value of the interview in the medical
      school admissions process and the availability of alternatives that allow better
      prediction and assessment of applicant performance.

PMID- 29379964
TI  - Diabetes and Hypertension in India: A Nationally Representative Study of 1.3
      Million Adults.
AB  - Importance: Understanding how diabetes and hypertension prevalence varies within
      a country as large as India is essential for targeting of prevention, screening,
      and treatment services. However, to our knowledge there has been no prior
      nationally representative study of these conditions to guide the design of
      effective policies. Objective: To determine the prevalence of diabetes and
      hypertension in India, and its variation by state, rural vs urban location, and
      individual-level sociodemographic characteristics. Design, Setting, and
      Participants: This was a cross-sectional, nationally representative, population
      based study carried out between 2012 and 2014. A total of 1 320 555 adults 18
      years or older with plasma glucose (PG) and blood pressure (BP) measurements were
      included in the analysis. Exposures: State, rural vs urban location, age, sex,
      household wealth quintile, education, and marital status. Main Outcomes and
      Measures: Diabetes (PG level >=126 mg/dL if the participant had fasted or >=200
      mg/dL if the participant had not fasted) and hypertension (systolic BP>=140 mm Hg
      or diastolic BP>=90 mm Hg). Results: Of the 1 320 555 adults, 701 408 (53.1%)
      were women. The crude prevalence of diabetes and hypertension was 7.5% (95% CI,
      7.3%-7.7%) and 25.3% (95% CI, 25.0%-25.6%), respectively. Notably, hypertension
      was common even among younger age groups (eg, 18-25 years: 12.1%; 95% CI, 11.8%
      12.5%). Being in the richest household wealth quintile compared with being in the
      poorest quintile was associated with only a modestly higher probability of
      diabetes (rural: 2.81 percentage points; 95% CI, 2.53-3.08 and urban: 3.47
      percentage points; 95% CI, 3.03-3.91) and hypertension (rural: 4.15 percentage
      points; 95% CI, 3.68-4.61 and urban: 3.01 percentage points; 95% CI, 2.38-3.65).
      The differences in the probability of both conditions by educational category
      were generally small (<=2 percentage points). Among states, the crude prevalence
      of diabetes and hypertension varied from 3.2% (95% CI, 2.7%-3.7%) to 19.9% (95%
      CI, 17.6%-22.3%), and 18.0% (95% CI, 16.6%-19.5%) to 41.6% (95% CI, 37.8%-45.5%),
      respectively. Conclusions and Relevance: Diabetes and hypertension prevalence is
      high in middle and old age across all geographical areas and sociodemographic
      groups in India, and hypertension prevalence among young adults is higher than
      previously thought. Evidence on the variations in prevalence by state, age group,
      and rural vs urban location is critical to effectively target diabetes and
      hypertension prevention, screening, and treatment programs to those most in need.

PMID- 29379963
TI  - Circadian Rest-Activity Pattern Changes in Aging and Preclinical Alzheimer
      Disease.
AB  - Importance: Circadian rhythm disturbances occur in symptomatic Alzheimer disease
      (AD) and have been hypothesized to contribute to disease pathogenesis. However,
      it is unknown whether circadian changes occur during the presymptomatic phase of
      the disease. Objective: To examine the associations between circadian function,
      aging, and preclinical AD pathology in cognitively normal adults. Design,
      Setting, and Participants: This cross-sectional study was conducted using
      community volunteers from the Knight Alzheimer's Disease Research Center at
      Washington University in St Louis. Cognitively normal participants (n = 205)
      underwent 7 to 14 days of actigraphy in their home environment between 2010 and
      2012, in addition to clinical assessment, amyloid imaging with Pittsburgh
      Compound B (PiB), and cerebrospinal fluid biomarker collection. Data collected
      from 3 years before to 6 months after actigraphy were included. Sixteen
      participants were excluded owing to incomplete data collection. Main Outcomes and
      Measures: Circadian rhythm analysis was performed on actigraphy data using 3
      methods: cosinor, nonparametric, and empirical mode decomposition. Preclinical AD
      was assessed by longitudinal clinical assessment, amyloid imaging with PiB, and
      cerebrospinal fluid biomarker collection. Results: Data from 189 participants
      were included in the analyses. The mean (SD) age was 66.6 (8.3) years, and 121
      participants (64%) were women. Older age (beta = .247; P = .003) and male sex
      (beta = .170; P = .04), in the absence of amyloid pathology, were associated with
      a significant increase in intradaily variability, a nonparametric measure of rest
      activity rhythm fragmentation, as well as decreased amplitude by several
      measures. After correction for age and sex, the presence of preclinical amyloid
      plaque pathology, assessed by positive PiB imaging (mean [SD], 0.804 [0.187] for
      PiB negative vs 0.875 [0.178] for PiB positive; P = .05) or increasing
      cerebrospinal fluid phosphorylated-tau to amyloid beta 42 ratio (beta = .231; P =
      .008), was associated with increased intradaily variability, indicating rest
      activity rhythm fragmentation. Conclusions and Relevance: Preclinical AD is
      associated with rest-activity rhythm fragmentation, independent of age or sex.
      Aging was also associated with circadian dysfunction independently of preclinical
      AD pathology, particularly in men. The presence of circadian rhythm abnormalities
      in the preclinical phase of AD suggests that circadian dysfunction could
      contribute to early disease pathogenesis or serve as a biomarker of preclinical
      disease.

PMID- 29379966
TI  - Conceptualizing Addiction From an Osteopathic Perspective: Dopamine Homeostasis.
AB  - Addiction is a public health crisis in the United States. Understanding the cause
      and providing effective treatment for patients-in particular, those with
      substance use disorders-is challenging. Research has demonstrated that addiction
      is not a flaw in one's moral fiber or a disease of choice; rather, it is driven
      by alterations in neuronal mechanisms, especially those that involve the
      neurotransmitter dopamine, which plays a critical role in the brain's reward
      pathway. Much of osteopathic philosophy is based on the concept of total body
      homeostasis and allostasis. This article discusses the role of achieving dopamine
      homeostasis as part of a comprehensive biopsychosocial treatment strategy in the
      effective management of addiction. The authors aim to motivate osteopathic
      primary care physicians to incorporate osteopathic philosophy into the treatment
      of patients with substance use disorders.

PMID- 29379968
TI  - Aspiration of Dental Crown.

PMID- 29379967
TI  - Development of Neuromyelitis Optica Spectrum Disorder and Spinal Arachnoid Cysts
      in a Patient With Intractable Epilepsy.
AB  - Neuromyelitis optica is an inflammatory, demyelinating disease of the central
      nervous system that is characterized by severe relapsing attacks of optic
      neuritis and transverse myelitis. The current case describes a 29-year-old man
      with intractable epilepsy and diplegic spastic cerebral palsy who was given the
      diagnosis of neuromyelitis optica spectrum disorder after presenting with
      weakness, incontinence, and decreased visual acuity. His symptoms recurred 21
      months after initial presentation. Magnetic resonance imaging of his spine
      revealed arachnoid cysts with regional mass effects. Differentiation of arachnoid
      cysts from a demyelinating process may be difficult in the early stages of the
      disease. Close monitoring of patients with neuromyelitis optica spectrum disorder
      is important, especially in patients with recurrent or refractory symptoms.

PMID- 29379969
TI  - Model to Reduce Unintentional Firearms Injury and Death: Safety Through
      Education.

PMID- 29379970
TI  - Correction.

PMID- 29379971
TI  - Contemporary Routes of Cannabis Consumption: A Primer for Clinicians.
AB  - Although cannabis use is federally prohibited, medical cannabis is legal in some
      form in 30 states and the District of Columbia, and recreational use is legal in
      8 states and the District of Columbia. The increasing legal acceptance of
      cannabis has led to a burgeoning industry that is producing an expanding variety
      of cannabis products. Physicians and other health care professionals should be
      aware of modern forms of cannabis consumption, as well as variations in
      tetrahydrocannabinol concentrations, to improve assessment of cannabis use and
      approach to treatment. This review aims to familiarize clinicians with modern
      forms of cannabis consumption and enable comparisons between disparate cannabis
      products.

PMID- 29379973
TI  - Reducing Patient No-Shows: An Initiative at an Integrated Care Teaching Health
      Center.
AB  - Background: Patient no-shows impede the effectiveness and efficiency of health
      care services delivery. Objective: To evaluate a 2-phase intervention to reduce
      no-show rates at an integrated care community health center that incorporates a
      teaching program for osteopathic family medicine residents. Methods: The Elmont
      Teaching Health Center (ETHC) is 1 of 5 community-based health centers comprising
      the Long Island Federally Qualified Health Centers. In August 2015, the ETHC
      implemented a centerwide No-Show Rates Reduction Initiative divided into an
      assessment phase and implementation phase. The assessment phase identified
      reasons most frequently cited by patients for no-shows at the ETHC. The
      implementation phase, initiated in mid-September, addressed these reasons by
      focusing on reminder call verification, patient education, personal responses to
      patient calls, institutional awareness, and integration with multiple
      departments. To assess the initiative, monthly no-show rates were compared by
      quarter for 2015 and against rates for the previous year. Results: We recorded
      27,826 appointments with 6147 no-shows in 2014 and 31,696 appointments with 5690
      no-shows in 2015. No-show rates in the first 3 quarters of 2015 (range, 18.2%
      20.0%) were slightly lower than the rates in 2014 (20.1%-23.4%) and then changed
      by an increasingly wide margin in the last quarter of 2015 (15.3%), leading to a
      significant year (2014, 2015) by quarter (Q1, Q2, Q3, Q4) interaction (P=.004).
      Also, the change observed in Q4 in 2015 differed significantly from Q1 (P=.017),
      Q2 (P=.004), and Q3 (P=.027) in 2015, while Q1, Q2, and Q3 in 2015 did not
      significantly differ from one another. Conclusion: No-show rates were
      successfully reduced after a 2-phase intervention was implemented at 1 health
      center within a larger health care organization. Future directions include
      dismantling the individual components of the intervention, evaluating the role of
      patient volumes in no-show rates, assessing patient outcomes (eg, costs, health)
      in integrative care settings that treat underserved populations, and evaluating
      family medicine residents' training on continuity of care and no-show rates.

PMID- 29379974
TI  - Prevalence of Homelessness by Gender in an Emergency Department Population in
      Pennsylvania.
AB  - Context: According to the US Department of Housing and Urban Development, nearly
      1.5 million people spend at least 1 night in an emergency shelter or transitional
      housing each year, and more than 500,000 people are homeless on a given night in
      the United States. To our knowledge, limited data exist regarding the prevalence
      of homelessness in ED patients by gender (male, female, and transgender).
      Objective: To assess the prevalence of homelessness by gender in 3 EDs in
      Pennsylvania. Methods: From May 2015 through February 2016, patients in 3 EDs
      were approached to take a 5-question homelessness screening survey. To
      participate, patients had to be aged at least 18 years, speak English, have
      capacity to complete the survey, be willing to participate, and not be critically
      ill. Frequency comparisons were made using chi2 analysis. Statistical
      significance was defined as P<=.05. Results: A total of 4395 patients were
      included in the analysis. The mean (SD) age of the participants was 50.8 (20.5)
      years; 2557 (58.2%) were women and 3 (0.07%) were transgender. No difference in
      the rate of homelessness was observed between men and women, with 135 of 1835 men
      (7.4%) and 173 of 2557 women (6.8%) screening positive for homelessness (P=.472).
      Forty of 2557 women (1.6%) and 41 of 1835 men (2.2%) admitted they had slept
      outside or in an abandoned building, their car, an emergency shelter, or a hotel
      due to financial hardship in the past 60 days (P=.26). One transgender patient
      screened positive for homelessness. The mean age of participants who screened
      positive for homelessness was 40.9 (15.9) years. Conclusion: No significant
      difference was observed in the rate of homelessness between men and women in this
      ED population, which defies the perception that this issue primarily affects men.
      Public health interventions aimed at homeless populations should consider that
      both men and women may be equally affected by homelessness.

PMID- 29379975
TI  - Plantar Warts: Epidemiology, Pathophysiology, and Clinical Management.
AB  - Verrucae plantaris (plantar warts) are common cutaneous lesions of the plantar
      aspect of the foot that are caused by the human papillomavirus (HPV). Ubiquitous
      in our environment, asymptomatic infection with HPV occurs frequently, with most
      infections controlled or cleared by cellular and humoral immune responses.
      However, certain populations have been observed to manifest plantar warts at
      higher rates compared with the general population, placing them at increased risk
      for wart-induced pain and complications. Plantar warts shed HPV, which can then
      infect other sites in the plantar region or spread to other people. Although
      controlling risk factors is useful in preventing infection, the pervasive nature
      of HPV makes these preventive measures frequently impractical. This literature
      review outlines the current knowledge regarding the relationship between plantar
      wart pathophysiology, HPV transmission, and epidemiologic characteristics. Given
      the high propensity for treatment resistance of plantar warts and no established,
      practical, and reliable method of prevention, HPV prophylaxis for populations
      that demonstrate high rates of plantar warts may be of benefit in controlling the
      spread of lesions.

PMID- 29379976
TI  - OMT to Address the Physiologic Effects of Stress.

PMID- 29379977
TI  - Toe Gangrene Associated with Macroangiopathy in Systemic Sclerosis: A Case Series
      on the Unreliability of the Ankle-brachial Pressure Index.

PMID- 29379978
TI  - Outcome of Combined Treatment of Surgery and Adjuvant Radiotherapy in Merkel Cell
      Carcinoma.
AB  - In recent analyses of Merkel cell carcinoma, prognosis is poor even in stages I
      and II. We performed a monocentric retrospective study of 37 consecutive cases
      with Merkel cell carcinoma stage I to III treated with a combination of surgery
      and adjuvant radiation to evaluate progression-free and overall survival. The
      median primary tumour diameter was 17.9 mm. Cases consisted of 31 primary
      tumours, of which 13 had negative sentinel lymph node biopsy (IA n = 10 and IIA n
      = 3) and 18 no sentinel lymph node biopsy (IB n = 15 and IIB n = 3), 2 tumours
      with positive sentinel lymph node biopsy (IIIA) and 4 with local macrometastasis
      (IIIB). The median age was 71 years and the median follow-up was 60.4 months. The
      5-year progression-free survival was 83.8% and 5-year disease-specific survival
      was 95.7% (overall survival 93.0%). So far, our results show a high survival rate
      with combined treatment of surgery and adjuvant radiotherapy in early tumour
      stages of Merkel cell carcinoma.

PMID- 29379979
TI  - Propionibacterium acnes Abundance Correlates Inversely with Staphylococcus
      aureus: Data from Atopic Dermatitis Skin Microbiome.
AB  - The microbiome may influence disease severity in atopic dermatitis. The skin of
      atopic dermatitis patients and healthy individuals was sampled in a standardized
      manner and the microbial composition analysed using next-generation sequencing.
      Optical density measurements were used to investigate bacterial growth under
      defined conditions in vitro. Lesional skin from patients with atopic dermatitis
      had a higher abundance of Staphylococcus aureus and reduced quantities of
      Propionibacterium acnes and Lawsonella clevelandensis compared with non-lesional
      skin. The abundance of P. acnes correlated negatively with that of S. aureus
      (rho= -0.6501, p < 0.0001). Fermentation products of P. acnes inhibited the
      growth of S. aureus and S. epidermidis. Serum from patients with atopic
      dermatitis inhibited the growth of S. aureus to a greater extent than did serum
      from healthy individuals. These results suggest that selective modification of
      the skin microbiome could potentially be used as a therapeutic strategy in atopic
      dermatitis.

PMID- 29379980
TI  - Subtle Imaging Findings Aid the Diagnosis of Adolescent Hereditary Spastic
      Paraplegia and Ataxia.
AB  - PURPOSE: Hereditary spastic paraplegia (HSP) and hereditary spastic ataxia (HSA)
      are a heterogeneous group of genetic disorders characterized by progressive lower
      limb spasticity resulting from pyramidal tract dysfunction. By identifying
      critical imaging findings within the clinical context of spasticity, radiologists
      are uniquely positioned to recommend specific genetic testing, and thus
      facilitate diagnosis. METHODS: We present two examples of HSP and HSA that had
      gone clinically unrecognized for years, and in which magnetic resonance imaging
      played a critical role in the diagnosis. RESULTS: Radiologists' awareness of HSP
      and HSA, combined with a critical review of the clinical history and
      characteristic imaging findings led to specific genetic testing and a definitive
      diagnosis. CONCLUSION: Awareness of HSP and HSA among radiologists will expedite
      more accurate diagnosis, explanation of patient symptoms, recommendation for
      syndrome-specific treatment, and family planning considerations.

PMID- 29379981
TI  - TGF-beta-induced NKILA inhibits ESCC cell migration and invasion through NF
      kappaB/MMP14 signaling.
AB  - : The transforming growth factor beta (TGF-beta) signaling pathway plays anti-
      and pro-tumoral roles in the vast majority of cancers, and long noncoding RNAs
      have been reported to play key roles in the highly contextual response process.
      However, the roles of long noncoding RNAs (lncRNAs) in TGF-beta signaling in
      esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we
      performed RNA-seq to compare lncRNAs expression levels between TGF-beta1-treated
      and untreated ESCC cells and observed that NF-kappaB-interacting lncRNA (NKILA)
      was remarkably upregulated by the classical TGF-beta signaling pathway. RNA
      profiling of 39 pairs ESCC tumor and adjacent nontumor samples using RT-qPCR
      demonstrated that NKILA is significantly downregulated in ESCC tumor tissues, and
      NKILA expression levels were significantly decreased in advanced tumor tissues
      (III and IV) compared to early stages (I and II) (p < 0.01). Gain- and loss-of
      function assays showed that NKILA inhibited ESCC cell metastasis in vitro and in
      vivo, and mechanism studies showed that NKILA repressed MMP14 expression by
      inhibiting IkappaBalpha phosphorylation and NF-kappaB activation. Collectively,
      these findings suggest that the TGF-beta-induced lncRNA NKILA has potential as an
      antimetastasis therapy. KEY MESSAGES: Long noncoding RNA NKILA could be
      remarkably upregulated by classical TGF-beta signal pathway in ESCC. NKILA was
      significantly downregulated in esophageal squamous cell carcinoma and negatively
      correlated with TNM stage. NKILA inhibits ESCC cell metastasis via repressing
      MMP14 expression by suppressing the phosphorylation of IkappaBalpha and NF-kappaB
      activation.

PMID- 29379982
TI  - Peri-operative antibiotic treatment of bacteriuria reduces early deep surgical
      site infections in geriatric patients with proximal femur fracture: is it
      related?

PMID- 29379985
TI  - [Requirements for ventilation concepts in buildings - Part I: edu-cational
      institution].

PMID- 29379983
TI  - Biomechanical comparisons of current suspensory fixation devices for anterior
      cruciate ligament reconstruction.
AB  - PURPOSE: Cortical suspensory devices are routinely used for femoral side fixation
      of soft tissue graft in anterior cruciate ligament (ACL) reconstruction. The
      purpose of this study was to evaluate the biomechanical properties of a new
      adjustable loop device (GraftMax(r)) compared with established devices
      (EndoButton(r) and TightRope(r)) in ACL reconstruction and to investigate whether
      knotting the free end of TightRope could improve biomechanical properties.
      METHODS: The three cortical suspensory devices (GraftMax(r) Button; Conmed,
      EndoButton(r) CL; Smith & Nephew, and TightRope(r) RT; Arthrex) were tested under
      cyclic load (50-250 N for 1000 cycles) and pull-to-failure conditions at 50 mm/h
      in a device-only setup using a tensile testing machine. The TightRope was
      additionally tested with its free suture ends knotted. The statistical analyses
      were done with one-way analysis of variance (ANOVA) and post hoc Tukey HSD tests.
      RESULTS: There are significant differences in the load-to-failure among the
      devices. The EndoButton showed the highest mean failure load at 1204.7 N compared
      to other devices (GraftMax (914.2 N), knotted TightRope (868.1 N) and TightRope
      (800.1 N) (p < 0.001). The mean total displacement after 1000 cycles was 0.76 mm,
      2.11 mm, 1.56 mm and 1.38 mm for the EndoButton, GraftMax, TightRope, and knotted
      TightRope, respectively. The EndoButton showed significantly better properties
      than both the GraftMax (p = 0.000) and the TightRope (p = 0.020) but not the
      knotted TightRope (p = n.s.) in total displacement. However, there was no
      significant difference between the TightRope and GraftMax (p = n.s.). CONCLUSION:
      The fixed loop (EndoButton) showed significantly better mechanical properties in
      failure load and displacement than TightRope or GraftMax in this biomechanical
      study. However, the mechanical properties of the GraftMax is comparable to the
      TightRope. Moreover, the knotting of TightRope improved mechanical properties in
      total displacement more than TightRope, but not in failure load. CLINICAL
      RELEVANCE: The biomechanical properties of the GraftMax are comparable to the
      TightRope. The TightRope, when knotted, shows an improvement both in load to
      failure and cyclic displacement, though the differences are not significant.

PMID- 29379986
TI  - Ancient Diversification of Three-Finger Toxins in Micrurus Coral Snakes.
AB  - Coral snakes, most notably the genus Micrurus, are the only terrestrial elapid
      snakes in the Americas. Elapid venoms are generally known for their potent
      neurotoxicity which is usually caused by Three-Finger Toxin (3FTx) proteins.
      These toxins can have a wide array of functions that have been characterized from
      the venom of other elapids. We examined publicly available sequences from
      Micrurus 3FTx to show that they belong to 8 monophyletic clades that diverged as
      deep in the 3FTx phylogenetic tree as the other clades with characterized
      functions. Functional residues from previously characterized clades of 3FTx are
      not well conserved in most of the Micrurus toxin clades. We also analyzed the
      patterns of selection on these toxins and find that they have been diversifying
      at different rates, with some having undergone extreme diversifying selection.
      This suggests that Micrurus 3FTx may contain a previously underappreciated
      functional diversity that has implications for the clinical outcomes of bite
      victims, the evolution and ecology of the genus, as well as the potential for
      biodiscovery efforts focusing on these toxins.

PMID- 29379988
TI  - Aberrant intestinal microbiota in individuals with prediabetes.
AB  - AIMS/HYPOTHESIS: Individuals with type 2 diabetes have aberrant intestinal
      microbiota. However, recent studies suggest that metformin alters the composition
      and functional potential of gut microbiota, thereby interfering with the diabetes
      related microbial signatures. We tested whether specific gut microbiota profiles
      are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0
      mmol/l or HbA1c of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers
      of poor metabolic health. METHODS: In the present case-control study, we analysed
      the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin
      resistance, dyslipidaemia and low-grade inflammation and 134 age- and sex-matched
      individuals with normal glucose regulation. RESULTS: We found that five bacterial
      genera and 36 operational taxonomic units (OTUs) were differentially abundant
      between individuals with prediabetes and those with normal glucose regulation. At
      the genus level, the abundance of Clostridium was decreased (mean log2 fold
      change -0.64 (SEM 0.23), p adj  = 0.0497), whereas the abundances of Dorea,
      [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold
      change 0.51 (SEM 0.12), p adj  = 5 * 10-4; 0.51 (SEM 0.11), p adj  = 1 * 10-4;
      0.60 (SEM 0.21), p adj  = 0.0497; and 0.92 (SEM 0.21), p adj  = 4 * 10-4,
      respectively). The two OTUs that differed the most were a member of the order
      Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed
      lower abundance among individuals with prediabetes (mean log2 fold change -1.74
      (SEM 0.41), p adj  = 2 * 10-3 and -1.65 (SEM 0.34), p adj  = 4 * 10-4,
      respectively). Faecal transfer from donors with prediabetes or screen-detected,
      drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J
      mice did not induce impaired glucose regulation in recipient mice.
      CONCLUSIONS/INTERPRETATION: Collectively, our data show that individuals with
      prediabetes have aberrant intestinal microbiota characterised by a decreased
      abundance of the genus Clostridium and the mucin-degrading bacterium A.
      muciniphila. Our findings are comparable to observations in overt chronic
      diseases characterised by low-grade inflammation.

PMID- 29379990
TI  - [PET/MRI].
AB  - CLINICAL/METHODICAL ISSUE: Magnet resonance imaging (MRI) is an excellent
      anatomical reference method for the combination with positron emission tomography
      (PET). But MRI does not produce data, which can be directly used for attenuation
      correction of PET data, potentially compromising quantitative accuracy of PET.
      STANDARD RADIOLOGICAL METHODS: Hybrid-positron emission tomography/computed
      tomography (PET/CT) is an established standard diagnostic tool, particularly for
      staging and restaging in oncology. Attenuation correction of PET data is
      performed with a uMAP derived from low-dose-CT, considered as a robust method.
      METHODICAL INNOVATIONS: Using standardized MRI-sequences, tissue classes are
      segmented and attenuation maps are obtained, based on empirical density values.
      In addition, new reconstruction algorithms and the possibility to acquire PET and
      MRI simultaneously with MRI-based motion correction are available. These advances
      have improved image quality and quantitative accuracy of the PET-data in PET/MRI.
      PERFORMANCE: In numerous oncological studies PET/CT and PET/MR were rated as
      equal in their diagnostic performance. The combination of functional-metabolic
      PET and multiparametric MRI with excellent soft tissue contrast complement each
      other with regard to their diagnostic information in numerous tumor entities.
      PRACTICAL RECOMMENDATIONS: The standard diagnostic workup for lung cancer is
      currently still based on PET/CT. In numerous tumor entities, the combination of
      PET/MRI can provide additional diagnostic information.

PMID- 29379989
TI  - Modulation of Excitability of Stellate Neurons in the Ventral Cochlear Nucleus of
      Mice by ATP-Sensitive Potassium Channels.
AB  - Major voltage-activated ionic channels of stellate cells in the ventral part of
      cochlear nucleus (CN) were largely characterized previously. However, it is not
      known if these cells are equipped with other ion channels apart from the voltage
      sensitive ones. In the current study, it was aimed to study subunit composition
      and function of ATP-sensitive potassium channels (KATP) in stellate cells of the
      ventral cochlear nucleus. Subunits of KATP channels, Kir6.1, Kir6.2, SUR1, and
      SUR2, were expressed at the mRNA level and at the protein level in the mouse VCN
      tissue. The specific and clearly visible bands for all subunits but that for
      Kir6.1 were seen in Western blot. Using immunohistochemical staining technique,
      stellate cells were strongly labeled with SUR1 and Kir6.2 antibodies and
      moderately labeled with SUR2 antibody, whereas the labeling signals for Kir6.1
      were too weak. In patch clamp recordings, KATP agonists including cromakalim (50
      uM), diazoxide (0.2 mM), 3-Amino-1,2,4-triazole (ATZ) (1 mM), 2,2-Dithiobis (5
      nitro pyridine) (DTNP) (330 uM), 6-Chloro-3-isopropylamino- 4H-thieno[3,2-e]
      1,2,4-thiadiazine 1,1-dioxide (NNC 55-0118) (1 uM), 6-chloro-3
      (methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (NN414)
      (1 uM), and H2O2 (0.88 mM) induced marked responses in stellate cells,
      characterized by membrane hyperpolarization which were blocked by KATP
      antagonists. Blockers of KATP channels, glibenclamide (0.2 mM), tolbutamide (0.1
      mM) as well as 5-hydroxydecanoic acid (1 mM), and catalase (500 IU/ml) caused
      depolarization of stellate cells, increasing spontaneous action potential firing.
      In conclusion, KATP channels seemed to be composed dominantly of Kir 6.2 subunit
      and SUR1 and SUR2 and activation or inhibition of KATP channels regulates firing
      properties of stellate cells by means of influencing resting membrane potential
      and input resistance.

PMID- 29379993
TI  - Estimated cerebral perfusion pressure among post-cardiac arrest survivors.

PMID- 29379991
TI  - Metformin potentiates cognitive and antidepressant effects of fluoxetine in rats
      exposed to chronic restraint stress and high fat diet: potential involvement of
      hippocampal c-Jun repression.
AB  - Several hypotheses link high fat diet (HFD) with the pathophysiology of
      depression and its response to antidepressants. This study aimed to determine the
      effect of metformin (MET) on the cognitive and antidepressant activity of
      fluoxetine (FLU) through its effect on c-Jun expression. Behavioral, cognitive
      function, biochemical, and histopathological studies were performed in non-HFD-
      and HFD-fed rats exposed to chronic restraint stress (CRS). Stressed group showed
      cognitive impairment, depressive-like symptoms, disturbed glucose homeostasis and
      lipid profile, reduced adiponectin level, brain-derived neurotrophic factor
      (BDNF) expression, and increased corticosterone and c-Jun. All these were
      aggravated by HFD. MET, FLU and their combination produced significant
      improvement in lipid profile with significant increase in adiponectin and BDNF
      expression. Corticosterone, body weight and insulin resistance showed significant
      decrease in the treated groups. Moreover, there was a significant decrease in
      hippocampal c Jun expression. There was a significant preferable effect toward
      the combination. Conclusion, MET may decrease the refractoriness to FLU and
      improves the cognition in individuals who are fed on HFD.

PMID- 29379995
TI  - Evidence for encephalopsin immunoreactivity in interneurones and striosomes of
      the monkey striatum.
AB  - In this study, we examined the cellular distribution of encephalopsin (opsin 3;
      OPN3) expression in the striatum of non-human primates. In addition, because of
      our long standing interest in Parkinson's disease and neuroprotection, we
      examined whether parkinsonian (MPTP; 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine) insult and/or photobiomodulation (670 nm) had any impact on
      encephalopsin expression in this key area of the basal ganglia. Striatal sections
      of control naive monkeys, together with those that were either MPTP- and/or
      photobiomodulation-treated were processed for immunohistochemistry. Our results
      revealed two populations of striatal interneurones that expressed encephalopsin,
      one of which was the giant, choline acetyltransferase-containing, cholinergic
      interneurones. The other population had smaller somata and was not cholinergic.
      Neither cell group expressed the calcium-binding protein, parvalbumin. There was
      also rich encephalopsin expression in a set of terminals forming striosome-like
      patches across the striatum. Finally, we found that neither parkinsonian (MPTP)
      insult nor photobiomodulation had any effect on encephalopsin expression in the
      striatum. In summary, our results revealed an extensive network of encephalopsin
      containing structures throughout the striatum, indicating that external light is
      in a position to influence a range of striatal activities at both the
      interneurone and striosome level.

PMID- 29379992
TI  - Decreased susceptibility to chlorhexidine affects a quarter of Escherichia coli
      isolates responsible for pneumonia in ICU patients.

PMID- 29379996
TI  - Toxicity of Nickel on the Selected Species of Marine Diatoms and Copepods.
AB  - Toxicity values for nickel on marine diatoms and copepods were derived based on
      bioassay tests. The 96 h IC50 of nickel on diatoms, Odontella mobiliensis and
      Coscinodiscus centralis were 0.31 +/- 0.01 and 0.62 +/- 0.02 mg/L and LC50 values
      on copepods, Oithona similis and Acartia danae were 2.78 +/- 0.14 and 2.34 +/-
      0.32 mg/L, respectively. The species mean chronic values of nickel were 0.016,
      0.17, 0.57 and 0.42 mg/L for O. mobiliensis, C. centralis, O. similis and A.
      danae, respectively. A hazardous concentration was derived and evaluated using
      the species sensitivity distribution (SSD) method. SSD indicated that 13 ug Ni/L
      is the maximum allowable concentration for protection of 95% plankton species in
      coastal and marine ecosystem of India. Diatoms are more sensitive to nickel than
      copepods by almost an order of magnitude. The toxicity values derived in the
      present study may be useful to calculate ambient water quality criteria/standard
      for nickel.

PMID- 29379997
TI  - Quality of life following vaginal reconstructive versus obliterative surgery for
      treating advanced pelvic organ prolapse.
AB  - INTRODUCTION AND HYPOTHESIS: Although colpocleisis is effective in selected
      women, the low-morbidity obliterative procedure for treating pelvic organ
      prolapse (POP) and its impact on postoperative quality of life (QOL) have rarely
      been studied. Our aim was to assess QOL in women after colpocleisis and compare
      it with that of women after reconstructive vaginal surgery. METHODS: This
      retrospective cohort study included women (aged 35-85 years) with POP who
      underwent obliterative or reconstructive surgical correction during 2009-2015.
      Patients who met the inclusion criteria underwent telephone interviews that
      included the validated Prolapse QOL questionnaire (P-QOL Thai). RESULTS: Of 295
      potential participants, 197 (67%) completed the questionnaire: 93 (47%) with
      obliterative and 104 (53%) with reconstructive surgery. Most were Thai (95.4%),
      multiparous (87%), and sexually inactive (76%). Their histories included
      hysterectomy (12%), incontinence or prolapse surgery (11%), and POP stage 3/4
      (77%). Patients undergoing obliterative surgery were significantly older than
      those undergoing a reconstructive procedure (69 vs 58 years, P < 0.05). The
      obliterative group had more children, less education, and more advanced POP.
      There were no significant differences in operative parameters or complications.
      The obliterative surgery group had a significantly shorter hospital stay: median
      2 (range 1-17) days vs 3 (1-20) days (P = 0.016). P-QOL scale revealed
      significantly less postoperative impairment in the obliterative surgery group
      (1.75 vs 5.26, P = 0.023). There were no significant differences in other P-QOL
      domains. CONCLUSIONS: Colpocleisis improves condition-specific QOL in selected
      patients with advanced POP and remains an option for this group. Surgeons should
      consider counseling elderly women with advanced POP about obliterative vaginal
      surgery.

PMID- 29379998
TI  - Road to recovery after transvaginal surgery for urethral mesh perforation:
      evaluation of outcomes and subsequent procedures.
AB  - INTRODUCTION AND HYPOTHESIS: Urethral injury resulting from transvaginal mesh
      slings is a rare complication with an estimated incidence of <1%. Our objective
      was to review the surgical management and functional outcomes of women presenting
      with urethral mesh perforation following midurethral sling (MUS) placement.
      METHODS: This was a retrospective multicenter review of women who from January
      2011 to March 2016 at two institutions underwent mesh sling excision for urethral
      perforation with Female Pelvic Medicine and Reconstructive Surgery fellowship
      trained surgeons. Data comprising preoperative symptoms, operative details, and
      postoperative outcomes were collected by telephone (n 13) or based on their last
      follow-up appointment. RESULTS OBTAINED: Nineteen women underwent transvaginal
      sling excision for urethral mesh perforation. Eight (42%) patients had undergone
      previous sling revision surgery. Sixty percent of women had resolution of their
      pelvic pain postoperatively. At follow-up, 92% reported urinary incontinence
      (UI), and three had undergone five additional procedures for vaginal prolapse
      mesh exposure (n 1), incontinence (onabotulinum toxin injection n 1, rectus
      fascia autologous sling n 1), prolapse (colpopexy n 1), and pain (trigger-point
      injection n 1). Patient global impression of improvement data was available for
      13 patients, of whom seven (54%) rated their postoperative condition as Very much
      better or Much better. CONCLUSIONS: The management of urethral mesh perforation
      is complex. Most women reported resolution of their pelvic pain and a high rate
      of satisfaction with their postoperative condition despite high rates of
      incontinence.

PMID- 29379999
TI  - Lumbar paraspinal muscle fat infiltration is independently associated with sex,
      age, and inter-vertebral disc degeneration in symptomatic patients.
AB  - PURPOSE: To determine the association of paraspinal muscles and psoas relative
      cross-sectional area (RCSA) and fat signal fraction (FSF) with sex, age, and
      intervertebral disc degeneration (IDD) in symptomatic patients. METHODS: We
      retrospectively evaluated 80 adult patients with spinal symptoms using T2
      weighted magnetic resonance images. We determined RCSA and FSF of the paraspinal
      muscles (erector spinae and multifidus) and psoas from L1-L2 to L5-S1; we
      determined IDD using the Pfirrmann classification. We compared differences in
      muscle RCSA and FSF based on sex and IDD, and we correlated age and IDD with RCSA
      and FSF. Using multivariate linear regression analyses, we determined the impact
      of sex, age, and IDD on RCSA and FSF. RESULTS: Men exhibited larger psoas RCSA
      but not larger paraspinal muscles RCSA than women. Women had larger FSF in the
      paraspinal muscles and psoas. Increasing IDD was associated with larger FSF if
      >=2 Pfirrmann grades were observed. IDD correlated with FSF of the paraspinal
      muscles, and age correlated with FSF of the paraspinal muscles and psoas. IDD was
      less consistently correlated with RCSA, but age correlated negatively with RCSA
      of all three muscles. Linear regression analyses demonstrated that sex, age, and
      IDD were each independently associated with FSF of the paraspinal muscles;
      additionally, sex and age, but not IDD, were associated with psoas FSF. RCSA was
      less consistently influenced by these three variables. CONCLUSIONS: Sex, age, and
      IDD are independently associated with paraspinal muscles FSF; only sex and age
      influence psoas FSF.

PMID- 29380000
TI  - Tumor-induced osteomalacia in association with PTEN-negative Cowden syndrome.
AB  - Tumor-induced osteomalacia (TIO) is a rare paraneoplastic condition in which
      phosphaturic mesenchymal tumors (PMTs) secrete high levels of fibroblast growth
      factor 23 (FGF23) into the circulation. This results in renal phosphate wasting,
      hypophosphatemia, muscle weakness, bone pain, and pathological fractures. Recent
      studies suggest that fibronectin-fibroblast growth factor receptor 1 (FN1-FGFR1)
      translocations may be a driver of tumorigenesis. We present a patient with TIO
      who also exhibited clinical findings suggestive of Cowden syndrome (CS), a rare
      autosomal dominant disorder characterized by numerous benign hamartomas, as well
      as an increased risk for multiple malignancies, such as thyroid cancer. While CS
      is a clinical diagnosis, most, but not all, harbor a mutation in the tumor
      suppressor gene PTEN. Genetic testing revealed a somatic FN1-FGFR1 translocation
      in the FGF23-producing tumor causing TIO; however, a germline PTEN mutation was
      not identified. To our knowledge, this is the first reported case of concurrent
      TIO and CS.

PMID- 29380001
TI  - Joint-preserving treatment options for irreparable rotator cuff tears.
AB  - An irreparable cuff tear is defined as the inability to achieve direct repair of
      native tendon to the great tuberosity despite intra- and extra-articular release
      of the remaining tissue. Three distinct anatomic patterns are identified:
      posterosuperior cuff tears which involve the supraspinatus, infraspinatus and
      teres minor; anterosuperior tears which involve the supraspinatus and
      subscapularis; and global tears which comprise both. Subacromial debridement and
      tenotomy or tenodesis of the long head of the biceps are proposed for older
      patients with a functional but very painful shoulder. Partial repair-particularly
      the infraspinatus and the subscapularis-is indicated for young patients if the
      muscle is still trophic with a fatty infiltration less than 3. It can be combined
      with a tendon transfer. In irreparable posterosuperior tears, latissimus dorsi or
      lower trapezius transfer has been reported to improve active elevation and
      external rotation. In anterosuperior cuff tears, pectoralis major or latissimus
      transfer has been used. If the lack of external rotation is isolated with good
      active forward elevation, the L'Episcopo procedure is the procedure of choice.
      New techniques with a short follow-up have been proposed recently: implantation
      of a balloon-shaped, biodegradable spacer in the subacromial space to maintain
      the position of the humeral head and to facilitate deltoid action; capsular
      superior reconstruction with a fascia lata or an artificial graft implanted
      between the superior glenoid rim and the great tuberosity to reproduce the
      natural capsule of the supra- and infraspinatus and to stabilize the humeral
      head.

PMID- 29380002
TI  - Recanalization of Occluded Transjugular Intrahepatic Portosystemic Shunts Using
      the Rosch-Uchida Stiffening Cannula.
AB  - PURPOSE: To report the safety and efficacy of occluded transjugular intrahepatic
      portosystemic shunts (TIPS) recanalization using the stiffening cannula (SC)
      technique. MATERIALS AND METHODS: This is a retrospective, single-centre, single
      arm study, investigating the safety and efficacy of transjugular recanalization
      of occluded TIPS using the SC (Cook, Ind. USA), in cases of failure to cross the
      occlusion with standard angiographic catheters and balloons. Between October 2015
      and October 2017, a total of 15 TIPS revisions have been performed due to shunt
      occlusion. In all cases in which the initial standard approach to cross the
      lesion failed, the SC technique was used. The study's primary efficacy outcome
      measure was technical success, and primary safety outcome measure was immediate
      procedure-related complications rate. Secondary outcome measures included
      restenosis and peri-procedural adverse events rates. RESULTS: Among 15 patients
      with shunt occlusion, seven (7/15; 46.5%) were successfully crossed via
      transjugular access, using standard angiographic catheters. In the remaining
      eight patients (nine procedures), recanalization with the SC technique was
      performed. Technical success was 100%. No complications or peri-procedural
      adverse events were noted. Restenosis rate was 11.1% (1/9 cases) as only one case
      of re-occlusion was noted, 3 months following recanalization using sole balloon
      angioplasty and successfully retreated using the SC technique and stent graft
      deployment. CONCLUSIONS: The SC technique is a safe and efficient option for the
      recanalization of occluded TIPS, in cases in which conventional lesion crossing
      is not feasible, in order to avoid percutaneous transhepatic access or new TIPS
      creation.

PMID- 29380003
TI  - Correction to: Prognostic Factors in Overall Survival of Patients with
      Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90
      Radioembolization: Results in Therapy-Naive Patients.
AB  - The published article has an error in the first name initial of one of the
      authors. "M. Justinger" should be "C. Justinger" as shown in this erratum.

PMID- 29380004
TI  - Percutaneous Cholecystostomy: Long-Term Outcomes in 324 Patients.
AB  - PURPOSE: To report technical success and clinical outcome of cholecystostomy tube
      placement along with timing-and method-of tube removal. MATERIALS AND METHODS: A
      retrospective review of cholecystostomy tubes placed from January 2010 to
      September 2017 was performed at a single academic center. This search yielded
      1160 patients. Of these patients, 324 (27.9%) met inclusion criteria for
      cholecystostomy placement, 199 (61.4%) males and 125 (38.6%) females, with mean
      age of 67 years (range 6-101 years). The indication for cholecystostomy tube
      placement, technical success, surgical candidacy, medical comorbidities, clinical
      outcome, tube indwelling time, complications, and follow-up were recorded.
      RESULTS: Indications for cholecystostomy tube placement included: acute
      cholecystitis (n = 270; 83.3%), perforated cholecystitis (n = 22; 6.8%),
      emphysematous cholecystitis (n = 18; 5.6%), and other (n = 14; 4.3%). Technical
      success was 100%. Many patients had multiple medical comorbidities including
      (most commonly): debilitation (n = 211; 65.1%), cardiovascular disease (n = 194;
      59.9%), multisystem disease (n = 181; 55.9%), and malignancy (n = 131; 40.4%).
      After tube placement, 96 (29.6%) patients underwent definitive cholecystectomy,
      94 expired (29.0%), 36 (11.1%) had a patent cystic duct on follow-up
      cholangiogram and subsequent cholecystostomy removal, 14 (4.3%) underwent
      cholecystoscopy with stone removal, and 3 (0.9%) had liver transplantation. Forty
      five (13.9%) patients had indwelling tubes at the end of the study period. Mean
      tube indwelling time was 89 days (range 0-586 days). CONCLUSION: Technical
      success for cholecystostomy tube placement was 100% with all patients having
      clinical resolution of acute cholecystitis. Many patients were able to have tubes
      subsequently removed.

PMID- 29380005
TI  - Incidence and Predictors of Unsuspected Recurrent Laryngeal Nerve Lymph Node
      Metastases After Neoadjuvant Chemoradiotherapy in Patients with Esophageal
      Squamous Cell Carcinoma.
AB  - BACKGROUND: Radical lymph node (LN) dissection along the recurrent laryngeal
      nerve (RLN) area carries a substantial morbidity rate, and its usefulness in
      neoadjuvant chemoradiotherapy (nCRT)-treated esophageal cancer patients remains
      unclear. METHODS: This study was conducted in two Asian thoracic surgery centers.
      Patients with esophageal squamous cell carcinoma (ESCC) who were judged to be ycN
      RLN(-) after nCRT and received bilateral RLN LN dissection were eligible. The
      incidence of unsuspected RLN LN involvement was analyzed, and we used least
      absolute shrinkage and selection operator (LASSO) regression to identify its
      predictors. RESULTS: A total of 56 patients (53 males and 3 females; mean age: 55
      years) were included. The upper mediastinum-including the bilateral RLN area-was
      covered by the radiation field in 48 (85.3%) patients. Although all of them were
      judged as ycN-RLN(-), unsuspected RLN LN involvement was identified on
      pathological examination in 11 (19.6%) subjects, being the only positive nodal
      station in seven. LASSO regression identified the pre-nCRT RLN LN(cN-RLN) status
      as the only independent predictor of ypN-RLN positivity; in contrast, neither the
      tumor location nor the radiation dose to the upper mediastinum were independently
      associated with ypN-RLN(+). RLN nodal dissection resulted in positive LN
      discovery rates of 30.8 and 10% in ycN-RLN(-) patients who had positive and
      negative cN-RLNs before nCRT, respectively. Consequently, 23.1 and 6.7% of
      patients in each subgroup would have been understaged in the absence of RLN nodal
      dissection. CONCLUSION: Nearly one-fifth of ESCC patients who were judged to be
      ycN-RLN(-) unexpectedly had positive ypN-RLN. The pre-nCRT cN-RLN status plays a
      key role in the selection of patients that should undergo RLN LN dissection after
      nCRT.

PMID- 29380006
TI  - Short- and Long-Term (10-year) Results of an Organized, Population-Based Breast
      Cancer Screening Program: Comparative, Observational Study from Hungary.
AB  - BACKGROUND: A nationwide breast cancer screening program was introduced in
      Hungary in the year 2002 for women aged 45-65 years to be performed biannually.
      METHODS: To investigate and report the short-term and 10-year follow-up results,
      we analyzed our Breast Unit's prospectively led database of screened (Group A)
      and age-matched symptomatic (Group B) patients from 2002 to 2007. We compared the
      clinicopathologic features of tumors and the impact of screening on surgical
      treatment, as well as the overall (OS), disease-specific (DSS) and disease-free
      survival (DFS) of different groups. RESULTS: Data from 208 screen-detected and
      101 symptomatic patients between 45 and 65 years of age were examined. Screen
      detected women were younger (54 vs. 58.5 years; p = 0.001) had significantly
      smaller tumors (15.5 vs. 17 mm; p = 0.044), and more breast-conserving surgery
      (68.8 vs. 59.4%; p = 0.032). Survival statistics were not statistically different
      at the median follow-up of 123 months; however, there was a trend toward improved
      DFS in Group A (82.7 vs. 74.3%; p = 0.074). CONCLUSIONS: Our study showed a
      significant reduction in rates of mastectomy in the screen-detected group in the
      short term, which does not translate into better survival rates based on initial
      long-term data. In order to realize the real advantage of this newly enstated
      screening program, a longer period of investigation is needed.

PMID- 29380007
TI  - Safety and Feasibility of a Ketamine Package to Support Emergency and Essential
      Surgery in Kenya When No Anaesthetist is Available.

PMID- 29380008
TI  - Cost-Effectiveness of Minimally Invasive Esophagectomy for Esophageal Squamous
      Cell Carcinoma.
AB  - INTRODUCTION: The cost-effectiveness of minimally invasive esophagectomy (MIE)
      versus open esophagectomy (OE) for esophageal squamous cell carcinoma (ESCC) has
      not been established. Recent cost studies have shown that MIE is associated with
      a higher surgical expense, which is not consistently offset by savings through
      expedited post-operative recovery, therefore suggesting a questionable benefit of
      MIE over OE from an economic point of view. In the current study, we compared the
      cost-effectiveness of MIE versus OE for ESCC. MATERIALS AND METHODS: Between
      April 2000 and December 2013, a total of 251 consecutive patients undergoing MIE
      or OE for ESCC were enrolled. After propensity score (PS)-matching the MIE group
      with the OE group for clinical characteristics, 95 patients from each group were
      enrolled to compare the peri-operative outcomes, long-term survival, and cost.
      RESULTS: After PS-matching, the baseline characteristics were not significantly
      different between groups. Perioperative outcomes were similar in both groups. MIE
      was superior to OE with respect to a shorter intensive care unit (ICU) stay,
      while the complication rate (except for hoarseness) and survival were similar.
      Post-operative cost was significantly less in the MIE group due to a shorter ICU
      stay; however, reduced post-operative cost failed to offset the higher surgical
      expense of MIE. CONCLUSIONS: MIE for ESCC failed to show cost-effectiveness
      regarding overall expense in our study, but costs less in the postoperative care,
      especially for ICU care. More cost studies on MIE in other health care systems
      are warranted to verify the cost-effectiveness of MIE.

PMID- 29380009
TI  - Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell
      therapies-the German Cancer Consortium approach.
AB  - Adoptive transfer of T cells genetically modified by TCRs or CARs represents a
      highly attractive novel therapeutic strategy to treat malignant diseases. Various
      approaches for the development of such gene therapy medicinal products (GTMPs)
      have been initiated by scientists in recent years. To date, however, the number
      of clinical trials commenced in Germany and Europe is still low. Several hurdles
      may contribute to the delay in clinical translation of these therapeutic
      innovations including the significant complexity of manufacture and non-clinical
      testing of these novel medicinal products, the limited knowledge about the
      intricate regulatory requirements of the academic developers as well as
      limitations of funds for clinical testing. A suitable good manufacturing practice
      (GMP) environment is a key prerequisite and platform for the development,
      validation, and manufacture of such cell-based therapies, but may also represent
      a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and
      the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and
      regulators to facilitate and advance early phase, academia-driven clinical
      trials. Starting with a workshop held in 2016, stakeholders from academia and
      regulatory authorities in Germany have entered into continuing discussions on a
      diversity of scientific, manufacturing, and regulatory aspects, as well as the
      benefits and risks of clinical application of CAR/TCR-based cell therapies. This
      review summarizes the current state of discussions of this cooperative approach
      providing a basis for further policy-making and suitable modification of
      processes.

PMID- 29380011
TI  - Effects of bisphenol A on ovarian follicular development and female germline stem
      cells.
AB  - Bisphenol A (BPA), one of the most frequently detected emerging pollutants in the
      environment, has been implicated in adverse effects in male and female
      reproduction at extremely low concentrations. This study aimed to investigate the
      effects and potential mechanism of BPA on mouse ovarian follicular development
      and female germline stem cells (FGSCs). Female CD-1 adult mice were administered
      gradient concentrations of BPA (12.5, 25, and 50 mg/kg/day) by intraperitoneal
      injection. We found that the number of atretic ovarian follicles was
      significantly increased at high BPA concentrations. Additionally, the numbers of
      primordial follicles, primary follicles, and corpus luteum (CL) were
      significantly reduced at high BPA concentrations. Interestingly, the number of
      FGSCs was remarkably reduced in BPA-treated ovaries. Furthermore, the increased
      apoptotic rate of FGSCs in vitro was triggered by BPA accompanied by increased
      BPA concentrations. To investigate the mechanism of BPA in ovarian follicular
      development, 193 differentially expressed proteins were identified in BPA-treated
      ovaries by the isobaric tags for relative and absolute quantification-coupled 2D
      liquid chromatography-mass spectrometry technique. A total of 106 proteins were
      downregulated and 85 proteins were upregulated. Among these proteins, the
      apoptosis-related protein SAFB-like transcriptional modulator (SLTM) was
      remarkably upregulated, and this result was consistent with western blotting.
      Taken together, our results suggest that an ovarian follicular development,
      especially, the development of primordial follicles, primary follicles, and the
      CL, is inhibited by high BPA concentrations, and the ovarian follicle atresia is
      initiated by BPA through upregulated expression of SLTM. Furthermore, BPA induces
      apoptosis of cultured FGSCs. The effect of BPA on ovarian follicular development
      and FGSCs, especially the effect on FGSCs, suggests a novel mechanism of how BPA
      causes female infertility.

PMID- 29380010
TI  - Increases in tibial force imbalance but not changes in tibiofemoral laxities are
      caused by varus-valgus malalignment of the femoral component in kinematically
      aligned TKA.
AB  - PURPOSE: The purposes of this study were to quantify the increase in tibial force
      imbalance (i.e. magnitude of difference between medial and lateral tibial forces)
      and changes in laxities caused by 2 degrees  and 4 degrees  of varus-valgus (V-V)
      malalignment of the femoral component in kinematically aligned total knee
      arthroplasty (TKA) and use the results to detemine sensitivities to errors in
      making the distal femoral resections. Because V-V malalignment would introduce
      the greatest changes in the alignment of the articular surfaces at 0 degrees 
      flexion, the hypotheses were that the greatest increases in tibial force
      imbalance would occur at 0 degrees  flexion, that primarily V-V laxity would
      significantly change at this flexion angle, and that the tibial force imbalance
      would increase and laxities would change in proportion to the degree of V-V
      malalignment. METHODS: Kinematically aligned TKA was performed on ten human
      cadaveric knee specimens using disposable manual instruments without soft tissue
      release. One 3D-printed reference femoral component, with unmodified geometry,
      was aligned to restore the native distal and posterior femoral joint lines. Four
      3D-printed femoral components, with modified geometry, introduced V-V
      malalignments of 2 degrees  and 4 degrees  from the reference component. Medial
      and lateral tibial forces were measured during passive knee flexion-extension
      between 0 degrees  to 120 degrees  using a custom tibial force sensor. Eight
      laxities were measured from 0 degrees  to 120 degrees  flexion using a six degree
      of-freedom load application system. RESULTS: With the tibial component
      kinematically aligned, the increase in the tibial force imbalance from that of
      the reference component at 0 degrees  of flexion was sensitive to the degree of V
      V malalignment of the femoral component. Sensitivities were 54 N/deg (medial
      tibial force increasing > lateral tibial force) (p < 0.0024) and 44 N/deg
      (lateral tibial force increasing > medial tibial force) (p < 0.0077) for varus
      and valgus malalignments, respectively. Varus-valgus malalignment did not
      significantly change varus, internal-external rotation, anterior-posterior, and
      compression-distraction laxities from 0 degrees  to 120 degrees  flexion. At only
      30 degrees  of flexion, 4 degrees  of varus malalignment increased valgus laxity
      1 degrees  (p = 0.0014). CONCLUSION: At 0 degrees  flexion, V-V malalignment of
      the femoral component caused the tibial force imbalance to increase
      significantly, whereas the laxities were relatively unaffected. Because tibial
      force imbalance has the potential to adversely affect patient-reported outcomes
      and satisfaction, surgeons should strive to limit errors in resecting the distal
      femoral condyles to within +/- 0.5 mm which in turn limits the average increase
      in tibial force imbalance to 68 N. Because laxities were generally unaffected,
      instability resulting from large increases in laxity is not a clinical concern
      within the +/- 4 degrees  range tested. LEVEL OF EVIDENCE: Therapeutic, Level II.

PMID- 29380012
TI  - Lymphocyte surface markers and cytokines are suitable for detection and potency
      assessment of skin-sensitizing chemicals in an in vitro model of allergic contact
      dermatitis: the LCSA-ly.
AB  - Allergic contact dermatitis is a widespread health disorder and occupational skin
      disease. Hence, screening for contact-sensitizing chemicals is highly relevant to
      toxicology, dermatology, and occupational medicine. The use of animal tests for
      this purpose is constrained by ethical considerations, need for high-throughput
      screening, and legislation (e.g., for cosmetics in the European Union). T cell
      activation is the final and most specific key event of the "adverse outcome
      pathway" for skin sensitization and therefore a promising target for the
      development of in vitro sensitization assays. We present a novel in vitro
      sensitization assay with a lymphocyte endpoint as an add-on to the loose-fit
      coculture-based sensitization assay (LCSA): the LCSA-ly. While the LCSA measures
      dendritic cell activation, the LCSA-ly offers the option for an additional
      lymphocyte endpoint which can be measured concurrently. We incorporated
      lymphocytes in our previously established coculture of primary human
      keratinocytes and monocyte-derived dendritic cells and tested nine substances:
      five sensitizers [2,4-dinitrochlorobenzene (DNCB) 1.25-15 umol/l, p
      phenylenediamine (PPD) 15.6-125 umol/l, 2-mercaptobenzothiazole (MBT) 50-1000
      umol/l, coumarin, and resorcinol (both: 250-1500 umol/l)] and four non
      sensitizers (monochlorobenzene, caprylic acid, glycerol, and salicylic acid (all:
      125-1000 umol/l)]. DNCB and MBT increased a subset of IL-23 receptor+/IFN-gamma
      receptor 1 (CD119)+ lymphocytes. DNCB, PPD, and MBT enhanced a subunit of the IL
      4 receptor (CD124) and a memory marker (CD44) on lymphocytes. Remarkably, DNCB,
      PPD, and MBT raised IL-4 concentrations in coculture supernatants while IFN-gamma
      levels decreased, which might point to Th2 activation in vitro. Coumarin,
      resorcinol, and non-sensitizers did not alter any of the tested surface markers
      or cytokines. IL-17 was not affected by any of the substances. Relative strength
      of sensitizers according to lymphocyte markers was DNCB > PPD > MBT, which
      corresponds to earlier results from the LCSA without lymphocyte endpoint, the
      murine local lymph node assay, and human data. This study is the first to prove
      the suitability of lymphocyte surface markers for sensitization testing and
      potency assessment.

PMID- 29380013
TI  - Bone Mineral Density Changes After 1 Year of Denosumab Discontinuation in
      Postmenopausal Women with Long-Term Denosumab Treatment for Osteoporosis.
AB  - The aim of the present study was to document the changes in bone mineral density
      (BMD) 1 year after denosumab loss-of-effect following long-term treatment with
      subcutaneous denosumab 60 mg Q6M during 7 or 10 years and in the absence of any
      treatment with a bone active substance. All postmenopausal women with
      osteoporosis who participated to the randomized placebo-controlled FREEDOM core
      trial and its open-label extension at the University Hospital of Bern,
      Switzerland, and who accepted to undergo off-treatment follow-up during 1 year
      after discontinuation, were included (N = 12). After 10 years of denosumab, mean
      lumbar spine (LS) BMD had increased by 21.2% vs. baseline. One year after
      discontinuation LS BMD had decreased by - 9.1% vs. Year 10, resulting in a net
      gain of 10.2% vs. baseline. At total hip (TH) and femoral neck (FN), BMD had
      increased by 8.3 and 8.1% in Year 10 vs. baseline, respectively. 1 Year after
      discontinuation, BMD had decreased by - 12.7 and - 11.0% vs. Year 10,
      respectively, corresponding to net BMD losses of - 5.5 and - 3.8% vs. baseline,
      respectively. Similar albeit less pronounced changes were observed in those
      treated with denosumab during 7 years. Stopping denosumab after long-term
      exposure resulted in BMD losses of large order of magnitude at all measured
      sites, suggesting that treatment duration may predict the rate and amount of bone
      lost.

PMID- 29380014
TI  - Bifunctional alanine dehydrogenase from the halotolerant cyanobacterium
      Aphanothece halophytica: characterization and molecular properties.
AB  - A link between carbon and nitrogen metabolism is important for serving as
      metabolic ancillary reactions. Here, we identified and characterized the alanine
      dehydrogenase gene in Aphanothece halophytica (ApalaDH) that is involved in
      alanine assimilation/dissimilation. Functional analysis revealed that ApalaDH
      encodes a bifunctional protein catalyzing the reversible reaction of pyruvate to
      L-alanine via its pyruvate reductive aminase (PvRA) activity, the reaction of L
      alanine to pyruvate via its alanine oxidative dehydrogenase activity, and the non
      reversible reaction of glyoxylate to glycine via its glyoxylate reductive aminase
      (GxRA) activity. Kinetic analysis showed the lowest affinity for pyruvate
      followed by L-alanine and glyoxylate with a Km of 0.22 +/- 0.02, 0.72 +/- 0.04,
      and 1.91 +/- 0.43 mM, respectively. ApalaDH expression was upregulated by salt.
      Only PvRA and GxRA activities were detected in vivo and both activities increased
      about 1.2- and 2.7-fold upon salt stress. These features implicate that the
      assimilatory/dissimilatory roles of ApAlaDH are not only selective for L-alanine
      and pyruvate, but also, upon salt stress, can catabolize glyoxylate to generate
      glycine.

PMID- 29380015
TI  - Voltammetric and electrogeneration approaches for the assessment of the oxidative
      drug metabolism.
AB  - In this paper, electrochemical (EC) methods have been proposed to evaluate the
      oxidative behavior of drugs as rapid, simple, and cheap strategies to predict
      some metabolic features. Various commercial drugs belonging to different
      therapeutic families have been assayed to deal with a wide variety of
      biotransformations and to cover different metabolism extents. First, differential
      pulse voltammetry has been applied to evaluate the oxidative behavior of drugs.
      Voltammetric assays have demonstrated to be highly efficient to predict the
      metabolism extent from the current intensity data. The second objective of this
      work has been the comparison of metabolite profiles from both EC and in vitro
      methods based on liver microsome assays. The resulting samples have been analyzed
      by reversed-phase liquid chromatography mode using a core-shell column and UV
      detection. Chromatographic methods have been established for each particular drug
      and its metabolites using 0.1% (v/v) formic acid aqueous solution and methanol
      (MeOH) as the components of the mobile phase. Drug oxidation products from both
      EC- and microsome-based methodologies have been compared in terms of variety and
      percentage from the corresponding chromatographic profiles. In general, most of
      the metabolites occurring in vitro have also been reproduced in the EC runs.
      Besides, it has been found that compositional profiles from EC experiments are
      dependent on experimental variables such as pH and potential. In general, acid
      (pH 2) and basic (pH 10) conditions and too high potentials can contribute to the
      generation of oxidation artifacts which differ from metabolites while milder
      potentials and neutral pH values may reproduce more accurately the microsome
      patterns. The proposed methodology is suitable for a first study of the oxidative
      behavior of molecules that can be related to relevant metabolic properties. The
      obtained information could be of great interest to prioritize or discard
      compounds, as a first screening, on the research of drug candidates.

PMID- 29380016
TI  - G-quadruplex aptamer selection using capillary electrophoresis-LED-induced
      fluorescence and Illumina sequencing.
AB  - One of the major difficulties that arises when selecting aptamers containing a G
      quadruplex is the correct amplification of the ssDNA sequence. Can aptamers
      containing a G-quadruplex be selected from a degenerate library using non
      equilibrium capillary electrophoresis (CE) of equilibrium mixtures (NECEEM) along
      with high-throughput Illumina sequencing? In this article, we present some
      mismatches of the G-quadruplex T29 aptamer specific to thrombin, which was PCR
      amplified and sequenced by Illumina sequencing. Then, we show the proportionality
      between the number of sequenced molecules of T29 added to the library and the
      number of sequences obtained in Illumina sequencing, and we find that T29
      sequences from this aptamer can be detected in a random library of ssDNA after
      the sample is fractionated by NECEEM, amplified by PCR, and sequenced. Treatment
      of the data by the counting of double-stranded DNA T29 sequences containing a
      maximum of two mismatches reveals a good correlation with the enrichment factor
      (fE). This factor is the ratio of the number of aptamer sequences found in the
      collected complex sample divided by the total number of sequencing reads (aptamer
      and non-aptamer) plus the quantity of T29 molecules (spiked into a DNA library)
      injected into CE.

PMID- 29380017
TI  - Dicationic ionic liquid thermal decomposition pathways.
AB  - The rapid expansion in the study and use of ionic liquids (ILs) is a result of
      their unique properties including negligible volatility, high thermal stability,
      and ability to dissolve disparate compounds. However, because ILs have infinitely
      variable structures (often referred to as "tunability"), these properties can
      differ considerably. Herein, we focus on the thermal stability of 15 bis
      /dicationic ionic liquids. Specifically, their thermal breakdown products are
      examined to determine the structural linkages, bonds, or atoms most susceptible
      to thermally induced changes and whether such changes occur before possible
      volatilization. In most cases, the heteroatom-carbon single bonds were
      susceptible to thermolytic decomposition. Graphical abstract Capture of
      dicationic ionic liquid thermal decomposition products for subsequent
      identification.

PMID- 29380018
TI  - Spatially resolved chemical analysis of cicada wings using laser-ablation
      electrospray ionization (LAESI) imaging mass spectrometry (IMS).
AB  - Laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS) is
      an emerging bioanalytical tool for direct imaging and analysis of biological
      tissues. Performing ionization in an ambient environment, this technique requires
      little sample preparation and no additional matrix, and can be performed on
      natural, uneven surfaces. When combined with optical microscopy, the
      investigation of biological samples by LAESI allows for spatially resolved
      compositional analysis. We demonstrate here the applicability of LAESI-IMS for
      the chemical analysis of thin, desiccated biological samples, specifically
      Neotibicen pruinosus cicada wings. Positive-ion LAESI-IMS accurate ion-map data
      was acquired from several wing cells and superimposed onto optical images
      allowing for compositional comparisons across areas of the wing. Various putative
      chemical identifications were made indicating the presence of hydrocarbons,
      lipids/esters, amines/amides, and sulfonated/phosphorylated compounds. With the
      spatial resolution capability, surprising chemical distribution patterns were
      observed across the cicada wing, which may assist in correlating trends in
      surface properties with chemical distribution. Observed ions were either (1)
      equally dispersed across the wing, (2) more concentrated closer to the body of
      the insect (proximal end), or (3) more concentrated toward the tip of the wing
      (distal end). These findings demonstrate LAESI-IMS as a tool for the acquisition
      of spatially resolved chemical information from fragile, dried insect wings. This
      LAESI-IMS technique has important implications for the study of functional
      biomaterials, where understanding the correlation between chemical composition,
      physical structure, and biological function is critical. Graphical abstract
      Positive-ion laser-ablation electrospray ionization mass spectrometry coupled
      with optical imaging provides a powerful tool for the spatially resolved chemical
      analysis of cicada wings.

PMID- 29380019
TI  - Performance of combined fragmentation and retention prediction for the
      identification of organic micropollutants by LC-HRMS.
AB  - In nontarget screening, structure elucidation of small molecules from high
      resolution mass spectrometry (HRMS) data is challenging, particularly the
      selection of the most likely candidate structure among the many retrieved from
      compound databases. Several fragmentation and retention prediction methods have
      been developed to improve this candidate selection. In order to evaluate their
      performance, we compared two in silico fragmenters (MetFrag and CFM-ID) and two
      retention time prediction models (based on the chromatographic hydrophobicity
      index (CHI) and on log D). A set of 78 known organic micropollutants was analyzed
      by liquid chromatography coupled to a LTQ Orbitrap HRMS with electrospray
      ionization (ESI) in positive and negative mode using two fragmentation techniques
      with different collision energies. Both fragmenters (MetFrag and CFM-ID)
      performed well for most compounds, with average ranking the correct candidate
      structure within the top 25% and 22 to 37% for ESI+ and ESI- mode, respectively.
      The rank of the correct candidate structure slightly improved when MetFrag and
      CFM-ID were combined. For unknown compounds detected in both ESI+ and ESI-,
      generally positive mode mass spectra were better for further structure
      elucidation. Both retention prediction models performed reasonably well for more
      hydrophobic compounds but not for early eluting hydrophilic substances. The log D
      prediction showed a better accuracy than the CHI model. Although the two
      fragmentation prediction methods are more diagnostic and sensitive for candidate
      selection, the inclusion of retention prediction by calculating a consensus score
      with optimized weighting can improve the ranking of correct candidates as
      compared to the individual methods. Graphical abstract Consensus workflow for
      combining fragmentation and retention prediction in LC-HRMS-based micropollutant
      identification.

PMID- 29380020
TI  - Comments on "Opinions on the Treatment Strategy after Breast Augmentation by
      Polyacrylamide Hydrogel Injection".

PMID- 29380021
TI  - Comments on "Alternative Rhinoplasty Technique: Rotational Spreader Flap (Rabbit
      Flap)".

PMID- 29380022
TI  - Nasal Alar Schwannoma: An Unusual Case Report.
AB  - PURPOSE: To present the second known case of nasal alar schwannoma, first since
      1973, with important considerations for surgical management. CASE REPORT: We
      present the case of a 25-year-old male with a 5-year history of progressively
      enlarging, non-tender, right alar mass with resultant ipsilateral nasal
      congestion and dyspnea secondary to nasal valve collapse. The mass was located
      cephalic to the mid-lateral aspect of the lower lateral crural cartilage, which
      extended to the pyriform aperture. The mass was removed in an en bloc fashion
      using an endonasal rhinoplasty approach with placement of an alar batten graft
      for valve stabilization. The surgical pathology of the mass was consistent with
      schwannoma. CONCLUSION: Regardless of the rarity, schwannoma should remain on the
      list of possible etiologies for a nasal alar mass. Depending on the size and
      concurrent mass effect, the external nasal valve may be compromised requiring
      careful evaluation and operative stabilization for optimal postsurgical outcome.
      LEVEL OF EVIDENCE V: This journal requires that authors assign a level of
      evidence to each article. For a full description of these Evidence-Based Medicine
      ratings, please refer to the Table of Contents or the online Instructions to
      Authors www.springer.com/00266 .

PMID- 29380023
TI  - Comparison of Facial Proportions Between Beauty Pageant Contestants and Ordinary
      Young Women of Korean Ethnicity: A Three-Dimensional Photogrammetric Analysis.
AB  - BACKGROUND: Although the harmony of facial proportions is traditionally perceived
      as an important element of facial attractiveness, there have been few objective
      studies that have investigated this esthetic balance using three-dimensional
      photogrammetric analysis. OBJECTIVES: To better understand why some women appear
      more beautiful, we investigated differences in facial proportions between beauty
      pageant contestants and ordinary young women of Korean ethnicity using three
      dimensional (3D) photogrammetric analyses. METHODS: A total of 43 prize-winning
      beauty pageant contestants (group I) and 48 ordinary young women (group II) of
      Korean ethnicity were photographed using 3D photography. Numerous soft tissue
      landmarks were identified, and 3D photogrammetric analyses were performed to
      evaluate 13 absolute lengths, 5 angles, 3 volumetric proportions, and 12 length
      proportions between soft tissue landmarks. RESULTS: Group I had a greater
      absolute length of the middle face, nose height, and eye height and width; a
      smaller absolute length of the lower face, intercanthal width, and nasal width; a
      larger nasolabial angle; a greater proportion of the upper and middle facial
      volume, nasal height, and eye height and width; and a lower proportion of the
      lower facial volume, lower face height, intercanthal width, nasal width, and
      mouth width. All these differences were statistically significant. CONCLUSIONS:
      These results indicate that there are significant differences between the faces
      of beauty pageant contestants and ordinary young women, and help elucidate which
      factors contribute to facial beauty. The group I mean values could be used as
      reference values for attractive facial profiles. LEVEL OF EVIDENCE V: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 29380024
TI  - Nanofat Increases Dermis Thickness and Neovascularization in Photoaged Nude Mouse
      Skin.
AB  - OBJECT: To investigate the effects of nanofat injection into photoaged nude mouse
      skin on dermis thickness, neovascularization, and cell proliferation. METHODS:
      Adipose-derived stem cells (ADSCs) and nanofat were prepared from human
      liposuction aspirates. The photoaged skin model was created using ultraviolet B
      (UVB) radiation onto BALB/c nude mice. A total of 24 mice were used in this
      study; 6 mice without treatment (natural aging) served as controls, while 18 mice
      were irradiated under the UVB lamp and treated with PBS (200 MUl per injection
      area), ADSCs (1 * 106/200 MUl ADSCs per injection area), or nanofat (200 MUl per
      injection area) on the dorsal skin. Four weeks after injection, skin specimens
      were collected. The skin texture of each group was evaluated by general
      observation. Histological analyses were performed to analyze skin structure,
      dermis thickness, collagen fiber arrangement, capillary density, and cell
      proliferation. RESULTS: Four weeks after injection, no obvious differences were
      observed between the PBS group, ADSCs group, and nanofat group by skin gross
      observation. From the histological analyses, the ADSCs group and the nanofat
      group showed obviously thicker dermis than the PBS group (P < 0.05). More
      capillaries were observed in skin using anti-CD31 staining in the ADSCs and
      Nanofat groups than was observed in the PBS group (P < 0.05). No significant
      differences in the average dermis proliferation index were observed between
      groups by anti-Ki-67 staining. However, an increased epidermal proliferation
      index was observed in the ADSCs and Nanofat groups, compared to that in the PBS
      group (P < 0.05). CONCLUSIONS: Nanofat increased dermis thickness and
      neovascularization in photoaged skin. NO LEVEL ASSIGNED: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 29380025
TI  - Physical activity and depression: is 150 min/week of moderate to vigorous
      physical activity a necessary threshold for decreasing risk of depression in
      adults? Different views from the same data.

PMID- 29380026
TI  - Involuntary hospitalization, stigma stress and suicidality: a longitudinal study.
AB  - People with severe mental illness and a history of involuntary hospitalization
      may experience stigma-related stress and suffer negative consequences as a
      result. However, the long-term impact of stigma stress on suicidality in this
      population remains unknown. This longitudinal study therefore examined stigma
      stress, self-stigma, self-esteem and suicidal ideation among 186 individuals with
      mental illness and recent involuntary hospitalization. After adjusting for age,
      gender, diagnoses and symptoms, more stigma stress at baseline predicted suicidal
      ideation after 2 years, mediated by increased self-stigma and decreased self
      esteem after 1 year. Anti-stigma interventions that reduce stigma stress and self
      stigma could therefore support suicide prevention.

PMID- 29380027
TI  - Honey Bee (Apis mellifera) Pollen Foraging Reflects Benefits Dependent on
      Individual Infection Status.
AB  - Parasites often modify host foraging behavior, for example, by spurring changes
      to nutrient intake ratios or triggering self-medication. The gut parasite, Nosema
      ceranae, increases energy needs of the European or Western honey bee (Apis
      mellifera), but little is known about how infection affects foraging behavior. We
      used a combination of experiments and observations of caged and free-flying
      individual bees and hives to determine how N. ceranae affects honey bee foraging
      behavior. In an experiment with caged bees, we found that infected bees with
      access to a high-quality pollen were more likely to survive than infected bees
      with access to a lower quality pollen or no pollen. Non-infected bees showed no
      difference in survival with pollen quality. We then tested free-flying bees in an
      arena of artificial flowers and found that pollen foraging bees chose pollen
      commensurate with their infection status; twice as many infected bees selected
      the higher quality pollen than the lower quality pollen, while healthy bees
      showed no preference between pollen types. However, healthy and infected bees
      visited sucrose and pollen flowers in the same proportions. Among hive-level
      observations, we found no significant correlations between N. ceranae infection
      intensity in the hive and the proportion of bees returning with pollen. Our
      results indicate that N. ceranae-infected bees benefit from increased pollen
      quality and will selectively forage for higher quality while foraging for pollen,
      but infection status does not lead to increased pollen foraging at either the
      individual or hive levels.

PMID- 29380028
TI  - Influence of Darkness and Aging on Marine and Freshwater Biofilm Microbial
      Communities Using Microcosm Experiments.
AB  - Ballast tank biofilms pose an additional risk of microbial invasion if sloughed
      off during ballasting operations, yet their significance and invasion biology is
      poorly understood. In this study, biofilms developed in marine and freshwater
      locations were exposed to prolonged darkness and aging by mimicking ballast water
      conditions in the laboratory. Upon prolonged darkness, the decay of
      phytoplankton, as indicated by the decrease in chlorophyll a in marine biofilms,
      led to remineralization and enhanced bacterial and protist populations. However,
      the same trend was not observed in the case of freshwater biofilms wherein the
      microbial parameters (i.e., bacteria, protists) and chlorophyll a decreased
      drastically. The bacterial community structure in such conditions was evaluated
      by real-time quantitative PCR (qPCR), and results showed that the biofilm
      bacterial communities changed significantly over a period of time. alpha
      Proteobacteria was the most stable taxonomic group in the marine biofilms under
      dark conditions. However, beta-proteobacteria dominated the freshwater biofilms
      and seemed to play an important role in organic matter remineralization. gamma
      Proteobacteria, which includes most of the pathogenic genera, were affected
      significantly and decreased in both the types of biofilms. This study revealed
      that marine biofilm communities were able to adapt better to the dark conditions
      while freshwater biofilm communities collapsed. Adaptation of tolerant bacterial
      communities, regeneration of nutrients via cell lysis, and presence of grazers
      appeared to be key factors for survival upon prolonged darkness. However, the
      fate of biofilm communities upon discharge in the new environment and their
      invasion potential is an important topic for future investigation.

PMID- 29380029
TI  - Microbial Diversity of Hypersaline Sediments from Lake Lucero Playa in White
      Sands National Monument, New Mexico, USA.
AB  - Lake Lucero is a gypsum-rich, hypersaline, ephemeral playa located on the
      southern part of the Alkali Flat at the White Sands National Monument (WSNM), New
      Mexico, USA. This modern playa setting provides a dynamic extreme environment
      that changes from a freshwater lake to a hypersaline dry desert during the year.
      We investigated the microbial diversity (bacteria, archaea, and microbial
      eukaryotes) of the Lake Lucero sediments using 16S- and 18S-based amplicon
      sequencing approach and explored the diversity patterns in different geochemical
      microenvironments. Our results indicated that similar microbial communities, in
      particular bacterial communities colonized, were remarkably consistent across our
      depth profiles. Therefore, these communities show a first-order relevance on the
      environmental conditions (moisture content, oxygen content, and mineral
      composition). We found that Proteobacteria, Actinobacteria, Bacteroidetes,
      Firmicutes, and Gemmatimonadetes were the major bacterial phyla, while
      Cyanobacteria were present in relatively low abundances and appeared only at the
      surface. Genus level assessment reflected that Truepera, Delftia, and Pseudomonas
      were the predominant bacterial genera across all samples. Euryarchaeota was the
      major archaeal phylum in all the samples, while Candidatus Halobonum and
      Candidatus Nitrososphaera were the main genera. Diatoms were the dominant
      eukaryotic group in surface samples and Fungi, Ciliophora, Metazoa, and Nematodes
      were the other major groups. As expected, metabolic inference indicated that
      aerobic microbial communities were near surface colonizers, with anaerobic
      communities dominating with increasing depth. We demonstrated that these
      microbial communities could be used to characterize unique geochemical
      microenvironments enabling us to extrapolate these results into other terrestrial
      and possibly extraterrestrial environments with comparable geochemical
      characteristics.

PMID- 29380030
TI  - Bio-reinforced self-healing concrete using magnetic iron oxide nanoparticles.
AB  - Immobilization has been reported as an efficient technique to address the
      bacterial vulnerability for application in bio self-healing concrete. In this
      study, for the first time, magnetic iron oxide nanoparticles (IONs) are being
      practically employed as the protective vehicle for bacteria to evaluate the self
      healing performance in concrete environment. Magnetic IONs were successfully
      synthesized and characterized using different techniques. The scanning electron
      microscope (SEM) images show the efficient adsorption of nanoparticles to the
      Bacillus cells. Microscopic observation illustrates that the incorporation of the
      immobilized bacteria in the concrete matrix resulted in a significant crack
      healing behavior, while the control specimen had no healing characteristics.
      Analysis of bio-precipitates revealed that the induced minerals in the cracks
      were calcium carbonate. The effect of magnetic immobilized cells on the concrete
      water absorption showed that the concrete specimens supplemented with decorated
      bacteria with IONs had a higher resistance to water penetration. The initial and
      secondary water absorption rates in bio-concrete specimens were 26% and 22% lower
      than the control specimens. Due to the compatible behavior of IONs with the
      concrete compositions, the results of this study proved the potential application
      of IONs for developing a new generation of bio self-healing concrete.

PMID- 29380031
TI  - Temperature and nutrients as drivers of microbially mediated arsenic oxidation
      and removal from acid mine drainage.
AB  - Microbial oxidation of iron (Fe) and arsenic (As) followed by their co
      precipitation leads to the natural attenuation of these elements in As-rich acid
      mine drainage (AMD). The parameters driving the activity and diversity of
      bacterial communities responsible for this mitigation remain poorly understood.
      We conducted batch experiments to investigate the effect of temperature (20 vs 35
      degrees C) and nutrient supply on the rate of Fe and As oxidation and
      precipitation, the bacterial diversity (high-throughput sequencing of 16S rRNA
      gene), and the As oxidation potential (quantification of aioA gene) in AMD from
      the Carnoules mine (France). In batch incubated at 20  degrees C, the dominance
      of iron-oxidizing bacteria related to Gallionella spp. was associated with almost
      complete iron oxidation (98%). However, negligible As oxidation led to the
      formation of As(III)-rich precipitates. Incubation at 35  degrees C and nutrient
      supply both stimulated As oxidation (71-75%), linked to a higher abundance of
      aioA gene and the dominance of As-oxidizing bacteria related to Thiomonas spp. As
      a consequence, As(V)-rich precipitates (70-98% of total As) were produced. Our
      results highlight strong links between indigenous bacterial community composition
      and iron and arsenic removal efficiency within AMD and provide new insights for
      the future development of a biological treatment of As-rich AMD.

PMID- 29380032
TI  - Isolation and characterization of a heterologously expressed bacterial laccase
      from the anaerobe Geobacter metallireducens.
AB  - Bioinformatics has revealed the presence of putative laccase genes in diverse
      bacteria, including extremophiles, autotrophs, and, interestingly, anaerobes.
      Integrity of laccase genes in anaerobes has been questioned, since laccases
      oxidize a variety of compounds using molecular oxygen as the electron acceptor.
      The genome of the anaerobe Geobacter metallireducens GS-15 contains five genes
      for laccase-like multicopper oxidases. In order to show whether one of the
      predicted genes encodes a functional laccase, the protein encoded by GMET_RS10855
      was heterologously expressed in Escherichia coli cells. The His6-tagged enzyme
      (named GeoLacc) was purified to a large extent in the apoprotein, inactive form:
      incubation with CuSO4 allowed a 43-fold increase of the specific activity
      yielding a metallo-enzyme. The purified enzyme oxidized some of the typical
      laccase substrates, including 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic
      acid) (ABTS), syringaldazine, and 2,6-dimethoxyphenol (2,6-DMP), along with
      pyrogallol and K4[Fe(CN)6]. Temperature optimum was 75  degrees C and pH optimum
      for ABTS and 2,6-DMP oxidation was ~ 6.0. As observed for other laccases, the
      enzyme was inhibited by halide anions and was sensitive to increasing
      concentrations of dimethyl sulfoxide and Tween-80. Notably, GeoLacc possesses a
      very high affinity for dioxygen: a similar activity was measured performing the
      reaction at air-saturated or microaerophilic conditions.

PMID- 29380033
TI  - Contrast-enhanced MRI after neoadjuvant chemotherapy of breast cancer: lesion-to
      background parenchymal signal enhancement ratio for discriminating pathological
      complete response from minimal residual tumour.
AB  - OBJECTIVES: To retrospectively investigate whether the lesion-to-background
      parenchymal signal enhancement ratio (SER) on breast MRI can distinguish
      pathological complete response (pCR) from minimal residual cancer following
      neoadjuvant chemotherapy (NAT), and compare its performance with the conventional
      criterion. METHODS: 216 breast cancer patients who had undergone NAT and MRI and
      achieved pCR or minimal residual cancer on surgical histopathology were included.
      Clinical-pathological features, SER and lesion size on MR images were analysed.
      Multivariate logistic regression, ROC curve and McNemar's test were performed.
      RESULTS: SER on early-phase MR images was independently associated with pCR (odds
      ratio [OR], 0.286 [95% CI: 0.113-0.725], p = .008 for Reader 1; OR, 0.306 [95%
      CI: 0.111-0.841], p = .022 for Reader 2). Compared with the conventional
      criterion, SER <=1.6 increased AUC (0.585-0.599 vs. 0.709-0.771, p=.001-.033) and
      specificity (21.9-27.4% vs. 80.8-86.3%, p <.001) in identifying pCR. SER <=1.6
      and/or size <=0.2 cm criterion showed the highest specificity of 90.4%.
      CONCLUSION: SER on early-phase MR images was independently associated with pCR,
      and showed improved AUC and specificity compared to the conventional criterion.
      The combined criterion of SER and size could be used to select candidates to
      avoid surgery in a future study. KEY POINTS: * Compared with conventional
      criterion, SER <= 1.6 criterion increased AUC and specificity. * Simple
      measurement of signal intensity could differentiate pCR from minimal residual
      cancer. * SER <=1.6 and/or size<=0.2cm criterion showed the highest specificity
      of 90.4 %. * The combined criterion could be used for a study to avoid surgery.

PMID- 29380034
TI  - Solitary Cholinergic Stimulation Induces Airway Hyperreactivity and Transcription
      of Distinct Pro-inflammatory Pathways.
AB  - Airway hyperreactivity is a hallmark feature of asthma and can be precipitated by
      airway insults, such as ozone exposure or viral infection. A proposed mechanism
      linking airway insults to airway hyperreactivity is augmented cholinergic
      transmission. In the current study, we tested the hypothesis that acute
      potentiation of cholinergic transmission is sufficient to induce airway
      hyperreactivity. We atomized the cholinergic agonist bethanechol to neonatal
      piglets and forty-eight hours later measured airway resistance. Bethanechol
      treated piglets displayed increased airway resistance in response to intravenous
      methacholine compared to saline-treated controls. In the absence of an airway
      insult, we expected to find no evidence of airway inflammation; however,
      transcripts for several asthma-associated cytokines, including IL17A, IL1A, and
      IL8, were elevated in the tracheas of bethanechol-treated piglets. In the lungs,
      prior bethanechol treatment increased transcripts for IFNgamma and its downstream
      target CXCL10. These findings suggest that augmented cholinergic transmission is
      sufficient to induce airway hyperreactivity, and raise the possibility that
      cholinergic-mediated regulation of pro-inflammatory pathways might contribute.

PMID- 29380035
TI  - The ontogeny of Limulus polyphemus (Xiphosura s. str., Euchelicerata) revised:
      looking "under the skin".
AB  - In recent years, methods for investigating the exo-morphology of zoological
      specimens have seen large improvements. Among new approaches, auto-fluorescence
      imaging offers possibilities to document specimens under high resolution without
      introducing additional artifacts as, for example, seen in scanning electron
      microscopy (SEM) imaging. Additionally, while SEM imaging is restricted to the
      outer morphology of the current instar, auto-fluorescence imaging can be used to
      document changes of the outer morphology of the next instar underneath the
      cuticle of the current instar. Thus, reinvestigating seemingly well known species
      with these methods may lead to interesting new insights. Here we reinvestigate
      the late embryonic development of the xiphosuran ("sword tail") Limulus
      polyphemus, which is often treated as a proxy for early eucheliceratan evolution.
      In addition to entire specimens, the appendages of the embryos were dissected off
      and documented separately with composite-autofluorescence microscopy. Based on
      these data, we can distinguish six developmental stages. These stages do not
      match exactly the formerly described stages, as these were largely based on SEM
      investigation. Our stages appear to represent earlier or later phases within what
      has in other studies been identified as one stage. This finer subdivision is
      visible as we can see the developing cuticle under the outer cuticle. In
      comparison to data from fossil xiphosurans, our results and those of other
      studies on the ontogeny of L. polyphemus point to a derived mode of development
      in this species, which argues against the idea of L. polyphemus as a "living
      fossil."

PMID- 29380037
TI  - A novel heterozygous ITGB3 p.T720del inducing spontaneous activation of integrin
      alphaIIbbeta3 in autosomal dominant macrothrombocytopenia with aggregation
      dysfunction.
AB  - We identified a novel heterozygous ITGB3 p.T720del mutation in a pedigree with
      macrothrombocytopenia exhibiting aggregation dysfunction. Platelet aggregation
      induced by ADP and collagen was significantly reduced, while ristocetin
      aggregation was normal. Integrin alphaIIbbeta3 was partially activated in a
      resting status, but platelet expression of alphaIIbbeta3 was downregulated.
      Functional analysis using a cell line showed spontaneous phosphorylation of FAK
      in alphaIIb/beta3 (p.T720del)-transfected 293T cells in suspension conditions.
      Abnormal cytoplasmic protrusions, membrane ruffling, and cytoplasmic localization
      of alphaIIbbeta3 were observed in alphaIIb/beta3 (p.T720del)-transfected CHO
      cells. Such morphological changes were reversed by treatment with an FAK
      inhibitor. These findings imply spontaneous, but partial, activation of
      alphaIIbbeta3 followed by phosphorylation of FAK as the initial mechanism of
      abnormal thrombopoiesis. Internalization and decreased surface expression of
      alphaIIbbeta3 would contribute to aggregation dysfunction. We reviewed the
      literature of congenital macrothrombocytopenia associated with heterozygous
      ITGA2B or ITGB3 mutations. Reported mutations were highly clustered at the
      membrane proximal region of alphaIIbbeta3, which affected the critical
      interaction between alphaIIb R995 and beta3 D723, resulting in a constitutionally
      active form of the alphaIIbbeta3 complex. Macrothrombocytopenia caused by a
      heterozygous activating mutation of ITGA2B or ITGB3 at the membrane proximal
      region forms a distinct entity of rare congenital thrombocytopenia.

PMID- 29380036
TI  - TYMS polymorphisms and responsiveness to or toxicity of methotrexate in
      rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to investigate whether the thymidylate
      synthase (TYMS) 2R/3R and 6 bp I/D polymorphisms can predict the response to or
      toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA).
      METHODS: We conducted a meta-analysis of studies on the association between the
      TYMS 2R/3R and 6 bp I/D polymorphisms and non-responsiveness to or toxicity of
      MTX in RA patients. RESULTS: A total of 11 studies involving 1613 patients were
      considered. Meta-analysis showed no association between the TYMS 2R/3R 3R allele
      and non-responsiveness to MTX therapy (odds ratio [OR] = 1.087, confidence
      interval [CI] = 0.682-1.731, p = 0.726). The meta-analysis indicated that there
      was no association between the TYMS 6 bp I/D D allele and non-responsiveness to
      MTX therapy (OR = 0.688, 95% CI = 0.281-1.683, p = 0.413). Meta-analysis revealed
      that the TYMS 2R/3R polymorphism was not associated with MTX toxicity, except for
      in a co-dominant model, and the TYMS 6 bp I/D polymorphism was not associated
      with MTX toxicity in all genetic models. CONCLUSIONS: This meta-analysis
      demonstrates that the TYMS 2R/3R and 6 bp I/D polymorphisms may not be associated
      with non-responsiveness to or toxicity of MTX therapy in RA patients.

PMID- 29380038
TI  - Mesenchymal stem cells transplantation in hematological patients with acute graft
      versus-host disease: characteristics and risk factors for infectious
      complications.
AB  - The role of MSCs in infection prevention and treatment is still discussed in
      transplant and hematological patients. The spectrum and risk factors for
      infections after MSCs transplantation in patients with acute GVHD have not been
      studied before. To determine the risk factors and spectrum of infectious
      complications in patients received mesenchymal stem cell transplantation as a
      treatment for acute GVHD. A prospective observational study was performed to
      evaluate the risk factors and characteristics of infectious complications after
      MSCs transplantation in adult patients having acute GVHD. Thirty-four episodes of
      MSCs transplantation in patients with acute GVHD after allogeneic HSCT were
      enrolled in the study. MSCs were given at a median dose of 1.32 (interquartile
      range 0.87-2.16) mln cells/kg per infusion at 91 days (interquartile range 31-131
      days) after HSCT. Data relating to age, gender, date, and type of
      transplantation, characteristics of MSCs, infectious agents, and antimicrobial
      therapy and prevention regimens were prospectively collected in all of the
      enrolled patients. The episode of proven infectious complication was set as a
      primary outcome. There were totally 68 patients with acute GVHD in the study;
      among them there were 34 cases of MSCs transplantation performed. Among the
      registered infectious episodes were viral infections (CMV-associated disease, EBV
      associated disease), invasive pulmonary aspergillosis, bacterial bloodstream
      infections, and pneumonia. MSCs transplantation has shown no statistically
      significant association with risk of infectious complications in patients with
      acute GVHD in a performed multivariate analysis. Among the most frequent
      infections in acute GVHD, we have described CMV, invasive aspergillosis, and
      bacterial infections (bloodstream infections or pneumonia). Among risk factors
      for infectious complications in patients with acute GVHD with/without MSCs
      transplantation are progression of main disease and neutropenia below 500
      cells/mm3 (for aspergillosis) and unrelated HSCT in the past history and
      progression of main disease (for bacterial bloodstream infections and pneumonia).

PMID- 29380039
TI  - Olfactory and gustatory functions after free flap reconstruction and radiotherapy
      for oral and pharyngeal cancer: a prospective follow-up study.
AB  - BACKGROUND: The senses of smell and taste can be adversely affected by both
      tumour- and treatment-related factors amongst head and neck cancer patients. The
      consequences may negatively impact nutritional status as well as quality of life
      in this patient population. PATIENTS AND METHODS: This prospective longitudinal
      follow-up study is consisted of 44 patients treated for oral cavity,
      oropharyngeal or hypopharyngeal cancer with tumour resection and microvascular
      free tissue transfer reconstruction at the Helsinki University Hospital,
      Helsinki, Finland. Thirty-nine (89%) of them also received radiotherapy. The
      senses of smell (odour detection, identification and threshold test) and taste
      (electrogustometry) and quality of life (UW-QOL) were evaluated preoperatively,
      and at 6 weeks, 3 months, 6 months and 12 months, postoperatively. RESULTS: There
      were higher scores in the odour detection values in the 6-week and 3-month tests
      compared with preoperative values for the tumour side. Other detection scores did
      not differ statistically from the preoperative values neither in the tumour nor
      the contralateral side. However, in the odour identification test, all
      posttreatment values were statistically significantly higher than pretreatment
      ones. In the olfactory threshold test, no statistically significant differences
      were found between pre- and posttreatment values. Electrogustometry values for
      the taste on the tumour side were statistically significantly impaired at 6 weeks
      (p < 0.05) and at 3 months (p < 0.01) compared with the pretreatment results.
      They were also impaired at 6 months and at 12 months, although the differences
      were not statistically significant. The quality of life was impaired after
      treatment in this patient series. However, the correlation between quality of
      life and sense of taste was found only at one time point (3 months) and only with
      contralateral side measurements. CONCLUSIONS: We conclude that in oral and
      pharyngeal cancer patients the postoperative taste problems are related to the
      impairment on the taste sensation in the tongue but not with the sense of smell.
      Moreover, the impairment in the quality of life is not clearly related to the
      impaired sense of taste.

PMID- 29380040
TI  - Sinonasal seromucinous hamartoma.
AB  - INTRODUCTION: Seromucinous hamartoma (SH) is a rare benign glandular
      proliferation of the sinonasal tract and nasopharynx. Only few cases have been
      reported in recent years. MATERIALS AND METHODS: We performed a retrospective
      medical record review of seven patients diagnosed with sinonasal SH who underwent
      endoscopic endonasal surgery. RESULTS: There were 5 males and 2 females, ranged
      in age from 40 to 98 years (mean 60 years, SD +/- 18.9). Two lesions arise from
      middle turbinate, two from uncinate process, and 3 (but 4 specimens) from nasal
      septum. Pathological features revealed a polypoid lesion with submucosal
      proliferation of seromucinous glands arranged in lobular and haphazard patterns.
      In immunohistochemical study, the seromucinous glands of SH were reactive for
      cytokeratin, including CK7, CK19, HMWK, but negative for CK20. CONCLUSION:
      Sinonasal SH is a rare diagnosis characterized by a polypoid lesion with a
      haphazard proliferation of seromucinous glands. The rhinologists should consider
      it in the differential diagnosis of a polypoid lesion in the nasal cavity.

PMID- 29380041
TI  - Pure laparoscopic anatomical segment VI resection using the Glissonian approach,
      Rouviere's sulcus as a landmark, and a modified liver hanging maneuver (with
      video).
AB  - BACKGROUND: Pure laparoscopic anatomical segmental resection has rarely been
      reported because this technique frequently presents technical difficulties. We
      describe the laparoscopic resection of anatomical segment VI using the Glissonian
      approach and a modified liver hanging maneuver. METHODS: Rouviere's sulcus is
      identified after retracting superiorly the gallbladder. The Glissonian approach
      for anatomical resection of segment VI can be performed with minimal dissection
      of the liver parenchyma around the sulcus. After clamping the Glissonian pedicle
      in the sulcus, the ischemic area fed by the portal pedicle was confirmed. The
      right triangular ligament was divided to create a small opening for placement of
      the hanging tape along the ischemic line. The liver parenchymal transection was
      performed along the hanging tape. RESULTS: Four patients underwent pure
      laparoscopic anatomical segment VI resection using the Glissonian approach and a
      modified liver hanging maneuver. The median operation time was 205 min (range,
      110-250 min), and median estimated blood loss was 110 mL (range, 100-350 mL). The
      median postoperative hospital stay was 5 days (range, 4-8 days). There was no
      postoperative morbidity or mortality. CONCLUSION: The Glissonian approach at
      Rouviere's sulcus as a landmark combined with the modified liver hanging maneuver
      may be safe and useful for laparoscopic anatomical segment VI resection.

PMID- 29380042
TI  - Evaluation of Pterin, a Promising Drug Candidate from Cyanide Degrading Bacteria.
AB  - Pterin is a member of the compounds known as pteridines. They have the same
      nucleus of 2-amino-4-hydroxypteridine (pterin); however, the side-chain is
      different at the position 6, and the state of oxidation of the ring may exist in
      different form viz. tetrahydro, dihydro, or a fully oxidized form. In the present
      study, the microorganisms able to utilize cyanide, and heavy metals have been
      tested for the efficient production of pterin compound. The soil samples
      contaminated with cyanide and heavy metals were collected from Salem steel
      industries, Tamil Nadu, India. Out of 77 isolated strains, 40 isolates were found
      to utilize sodium cyanate as nitrogen source at different concentrations.
      However, only 13 isolates were able to tolerate maximum concentration (60 mM) of
      sodium cyanate and were screened for pterin production. Among the 13 isolates,
      only 1 organism showed maximum production of pterin, and the same was identified
      as Bacillus pumilus SVD06. The compound was extracted and purified by preparative
      high-performance liquid chromatography and analyzed by UV/visible, FTIR, and
      fluorescent spectrum. The antioxidant property of the purified pterin compound
      was determined by cyclic voltammetry. In addition, antimicrobial activity of
      pterin was also studied which was substantiated by antagonistic activity against
      Escherichia coli, and Pseudomonas aeruginosa. Besides that the pterin compound
      was proved to inhibit the formation of biofilm. The extracted pterin compounds
      could be proposed further not only for antioxidant and antimicrobial but also for
      its potency to aid as anticancer and psychotic drugs in future.

PMID- 29380043
TI  - Patterns of circulating fat-soluble vitamins and carotenoids and risk of frailty
      in four European cohorts of older adults.
AB  - PURPOSE: To investigate the cross-sectional and prospective associations between
      patterns of serum fat-soluble micronutrients and frailty in four European cohorts
      of older adults 65 years of age and older. METHODS: Participants from the Three
      City (Bordeaux, France), AMI (Gironde, France), TSHA (Toledo, Spain) and
      InCHIANTI (Tuscany, Italy) cohorts with available data on serum alpha-carotene,
      beta-carotene, lycopene, cryptoxanthin, lutein + zeaxanthin, retinol, alpha
      tocopherol, gamma-tocopherol and 25-hydroxyvitamin D3 (25(OH)D) were included. A
      principal component (PC) analysis was used to derive micronutrient patterns.
      Frailty was defined using Fried's criteria. Multivariate logistic regression
      models adjusted for socio-demographic and health-related covariates were
      performed to assess the association between micronutrient patterns and prevalent
      frailty in 1324 participants, and the risk of frailty in 915 initially non-frail
      participants. RESULTS: Three different patterns were identified: the first
      pattern was characterized by higher serum carotenoids and alpha-tocopherol
      levels; the second was characterized by high loadings for serum vitamins A and E
      levels and low loadings for carotenes level; the third one had the highest
      loading for serum 25(OH)D and cryptoxanthin level and the lowest loading for
      vitamin A and E. A significant cross-sectional association was only observed
      between the seconnd PC and prevalent frailty (p = 0.02). Compared to the highest
      quartile, participants in the lowest quartile-i.e., high carotenes and low
      vitamins E and A levels-had higher odds of frailty (Odds ratio = 2.2; 95%
      confidence interval 1.3-3.8). No association with the risk of frailty was
      observed. CONCLUSIONS: These findings suggest that some specific micronutrient
      patterns are markers but not predictors of frailty in these European cohorts of
      older adults.

PMID- 29380044
TI  - Effects of daily walking on intermuscular adipose tissue accumulation with age: a
      5-year follow-up of participants in a lifestyle-based daily walking program.
AB  - PURPOSE: Intermuscular adipose tissue (IMAT) accumulates with age. However, there
      has been no long-term intervention study examining whether daily walking prevents
      or decreases the age-related IMAT accumulation. The purpose of this study was to
      determine effects of a long-term lifestyle-based daily walking program on age
      related IMAT accumulation after a 5-year follow-up. METHODS: Using a pedometer,
      daily step count was evaluated for 5 years in 24 middle-aged and elderly male and
      female participants. Using magnetic resonance imaging, thigh muscle, thigh
      subcutaneous adipose tissue, IMAT, abdominal subcutaneous adipose tissue, and
      visceral adipose tissue were examined at baseline and after 5 years. RESULTS:
      After 5 years, there was no significant increase in IMAT in all participants. In
      addition, IMAT significantly decreased in participants with a daily step count of
      > 9000 (4.0 +/- 2.1 vs. 3.1 +/- 1.6 cm2; p < 0.05). Moreover, changes in IMAT
      within 5 years correlated with changes in daily step counts, even after adjusting
      for confounding factors (p < 0.05). CONCLUSIONS: Long-term lifestyle-based daily
      walking program prevented the age-related IMAT accumulation in middle-aged and
      elderly adults. Furthermore, increased daily walking correlated with decreased
      IMAT over 5 years.

PMID- 29380045
TI  - Are there gender differences in associations of effort-reward imbalance at work
      with self-reported doctor-diagnosed depression? Prospective evidence from the
      German Socio-Economic Panel.
AB  - PURPOSE: Cohort studies established elevated risks of depression among employees
      experiencing psychosocial stress at work, defined by 'job strain' or 'effort
      reward imbalance' (ERI). Yet, conflicting evidence exists on whether the strength
      of these associations varies by gender. We explore this question in a nationally
      representative sample of working women and men where work stress (ERI) was
      related to reported depression over a 2-year follow-up. METHODS: Data were
      derived from the panel waves 2011 and 2013 of the German Socio-Economic Panel.
      Work stress was assessed by validated short scales of the ERI questionnaire, and
      doctor-diagnosed depression reported in 2013 (after excluding cases reported in
      2011) was used as outcome variable. The sample with full data in 2013 consisted
      of 6693 participants (49.4% women). RESULTS: In 2011, men scored significantly
      higher than women on the scale 'effort' and on the 'effort-reward ratio', whereas
      no significant gender differences for 'reward' and 'over-commitment' were
      observed. Women reported a diagnosed depression almost twice as often as men (4.2
      vs. 2.6%). Associations of all ERI scales with depression were statistically
      significant, with no noticeable differences in the strength of associations
      between women and men. Risk of depression was higher among men and women with
      effort-reward imbalance [RR (risk ratio) of 1.82; 95% CI (confidence interval)
      1.36-2.44 and RR of 1.88; 95% CI 1.51-2.33, respectively]. CONCLUSIONS: Despite
      higher effort and slightly higher effort-reward ratio among men interaction terms
      between gender, work stress and depression were generally not significant. While
      gender inequities in the labour market are persisting stress-reducing worksite
      health promotion programs should apply equally for men and women.

PMID- 29380047
TI  - Your move or mine? Music training and kinematic compatibility modulate
      synchronization with self- versus other-generated dance movement.
AB  - Motor simulation has been implicated in how musicians anticipate the rhythm of
      another musician's action to achieve interpersonal synchronization. Here, we
      investigated whether similar mechanisms govern a related form of rhythmic action:
      dance. We examined (1) whether synchronization with visual dance stimuli was
      influenced by movement agency, (2) whether music training modulated simulation
      efficiency, and (3) what cues were relevant for simulating the dance rhythm.
      Participants were first recorded dancing the basic Charleston steps paced by a
      metronome, and later in a synchronization task they tapped to the rhythm of their
      own point-light dance stimuli, stimuli of another physically matched participant
      or one matched in movement kinematics, and a quantitative average across
      individuals. Results indicated that, while there was no overall "self advantage"
      and synchronization was generally most stable with the least variable (averaged)
      stimuli, motor simulation was driven-indicated by high tap-beat variability
      correlations-by familiar movement kinematics rather than morphological features.
      Furthermore, music training facilitated simulation, such that musicians
      outperformed non-musicians when synchronizing with others' movements but not with
      their own movements. These findings support action simulation as underlying
      synchronization in dance, linking action observation and rhythm processing in a
      common motor framework.

PMID- 29380046
TI  - Low-pass single-chromosome sequencing of human small supernumerary marker
      chromosomes (sSMCs) and Apodemus B chromosomes.
AB  - Supernumerary chromosomes sporadically arise in many eukaryotic species as a
      result of genomic rearrangements. If present in a substantial part of species
      population, those are called B chromosomes, or Bs. This is the case for 70
      mammalian species, most of which are rodents. In humans, the most common types of
      extra chromosomes, sSMCs (small supernumerary marker chromosomes), are diagnosed
      in approximately 1 of 2000 postnatal cases. Due to low frequency in population,
      human sSMCs are not considered B chromosomes. Genetic content of both B
      chromosomes and sSMCs in most cases remains understudied. Here, we apply
      microdissection of single chromosomes with subsequent low-pass sequencing on Ion
      Torrent PGM and Illumina MiSeq to identify unique and repetitive DNA sequences
      present in a single human sSMC and several B chromosomes in mice Apodemus
      flavicollis and Apodemus peninsulae. The pipeline for sequencing data analysis
      was made available in Galaxy interface as an addition to previously published
      command-line version. Human sSMC was attributed to the proximal part of
      chromosome 15 long arm, and breakpoints leading to its formation were located
      into satellite DNA arrays. Genetic content of Apodemus B chromosomes was species
      specific, and minor alterations were observed in both species. Common features of
      Bs in these Apodemus species were satellite DNA and ERV enrichment, as well as
      the presence of the vaccinia-related kinase gene Vrk1. Understanding of the non
      essential genome elements content provides important insights into genome
      evolution in general.

PMID- 29380048
TI  - Endothelial function in children with white-coat hypertension.
AB  - Several studies have demonstrated endothelial dysfunction in patients with
      essential hypertension. However, the presence of endothelial dysfunction in
      children with white-coat hypertension has not been studied. We evaluated the
      endothelial function in children with white-coat hypertension and essential
      hypertension using a novel method based on the assessment of flow-mediated
      dilation (FMD). Study involved 106 children: 30 white-coat hypertensives (age
      16.3 +/- 1.3 years, mean +/- SD), 30 essential hypertensives (age 16.4 +/- 1.3
      years), and 46 healthy controls (age 16.2 +/- 1.4 years). Ultrasound scans of the
      right brachial artery were performed using Prosound F75 Aloka system during
      protocol: baseline (1 min), forearm ischemia (5 min), and post-occlusion phase (3
      min). FMD (%) was expressed as a change of the arterial diameter from baseline to
      maximum post-occlusion value and the values < 5% were considered as deficient
      FMD. We found significantly lower FMD in both essential and white-coat
      hypertension compared to control group (p < 0.05 for both) with no significant
      difference between the hypertensive groups. Deficient FMD was found in both
      hypertensive groups, but not in the control group. The occurence of deficient FMD
      was significantly higher in both essential and white-coat hypertensives compared
      to controls (p < 0.01 for both) with no significant difference between the
      hypertensive groups. Our findings of endothelial dysfunction indicated by
      impaired FMD in pediatric patients with white-coat hypertension could help to
      elucidate the mechanisms of the increased cardiovascular risk that could be
      similar as found in essential hypertension; therefore, white-coat hypertension
      should not be considered a benign phenomenon.

PMID- 29380049
TI  - Sense and antisense RNA are not toxic in Drosophila models of C9orf72-associated
      ALS/FTD.
AB  - A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common
      genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia.
      Neurodegeneration may occur via transcription of the repeats into inherently
      toxic repetitive sense and antisense RNA species, or via repeat-associated non
      ATG initiated translation (RANT) of sense and antisense RNA into toxic dipeptide
      repeat proteins. We have previously demonstrated that regular interspersion of
      repeat RNA with stop codons prevents RANT (RNA-only models), allowing us to study
      the role of repeat RNA in isolation. Here we have created novel RNA-only
      Drosophila models, including the first models of antisense repeat toxicity, and
      flies expressing extremely large repeats, within the range observed in patients.
      We generated flies expressing ~ 100 repeat sense or antisense RNA either as part
      of a processed polyadenylated transcript or intronic sequence. We additionally
      created Drosophila expressing > 1000 RNA-only repeats in the sense direction.
      When expressed in adult Drosophila neurons polyadenylated repeat RNA is largely
      cytoplasmic in localisation, whilst intronic repeat RNA forms intranuclear RNA
      foci, as does > 1000 repeat RNA, thus allowing us to investigate both nuclear and
      cytoplasmic RNA toxicity. We confirmed that these RNA foci are capable of
      sequestering endogenous Drosophila RNA-binding proteins, and that the production
      of dipeptide proteins (poly-glycine-proline, and poly-glycine-arginine) is
      suppressed in our models. We find that neither cytoplasmic nor nuclear sense or
      antisense RNA are toxic when expressed in adult Drosophila neurons, suggesting
      they have a limited role in disease pathogenesis.

PMID- 29380050
TI  - Tibial tunnel placement in anatomic anterior cruciate ligament reconstruction: a
      comparison study of outcomes between patient-specific drill template versus
      conventional arthroscopic techniques.
AB  - INTRODUCTION: Accurate anatomic graft tunnel positioning is essential for the
      successful application of anatomic anterior cruciate ligament (ACL)
      reconstruction. The accurate insertion of the tibial tunnel (TT) remains
      challenging. Here, we explored a novel strategy of patient-specific drill
      template (PDT) for the placement of TT in ACL reconstruction and assessed its
      efficacy and accuracy. MATERIALS AND METHODS: TT placement was randomized and
      performed by use of the PDT technique in 40 patients (PDT group) and the
      conventional arthroscopic technique in 38 patients (Arthroscopic group). After
      surgery, the deviations at the center point of the ACL tibial attachment area and
      radiological TT positioning were assessed in both groups. The preoperative and
      follow-up examinations included pivot-shift testing, KT-1000 arthrometer testing,
      the Lysholm and International Knee Documentation Committee scales were used to
      compare the knee stability and the functional state. RESULTS: The ideal center
      points achieved in the PDT group were more precise than that in the arthroscopic
      group (p < 0.001). Radiological TT positioning performed by use of the PDT
      technique was more accurate than that by the arthroscopic technique (p = 0.027).
      Statistical differences could not be found between the groups in terms of the
      pivot-shift test, KT-1000 arthrometer laxity measurements, the Lysholm or
      International Knee Documentation Committee scales. Both groups improved at follow
      up compared with the preoperative assessment in terms of the pivot-shift test,
      the laxity tests, and scoring scales. CONCLUSIONS: The novel PDT strategy could
      provide more accurate TT positioning than the traditional arthroscopic technique
      in ACL reconstruction. However, functional scales and stability tests gave
      similar results in the PDT and the standard techniques. LEVEL OF EVIDENCE: I.

PMID- 29380051
TI  - Long-term survival of Naegleria polaris from Antarctica after 10 years of storage
      at 4  degrees C.
AB  - A free-living amoeba, Naegleria is ubiquitously distributed in various natural
      environments. Since some Naegleria spp. are exclusively distributed in the Arctic
      and sub-Antarctic regions, we hypothesized that the amoeba may be useful to
      determine long-term survival of Naegleria in laboratory conditions at 4  degrees
      C. The main objective of the study is to determine that a species of an
      environmental amoebal isolated can live at low temperatures after a long time.
      Here, we therefore show long-term survival of an amoeba, Naegleria polaris
      isolated from a sediment sample, which was collected from Antarctica 10 years
      ago, and since stored at 4  degrees C. The sample was put on non-nutrient agar
      plates with heat-killed Escherichia coli, and then the plate was incubated at 4,
      15, or 30  degrees C. Motile amoebae were seen only when the plate was incubated
      at 15  degrees C. The sequencing of ribosomal DNA including internal transcribed
      spacers (ITS) 1, 5.8S rDNA, and ITS2 region revealed the amoebae to be N.
      polaris, which is exclusively distributed in the Arctic and sub-Antarctic
      regions. Scanning electron microscopic observation showed that no typical sucker
      like structure was seen on the surface of N. polaris, but the cysts were similar
      to those of Naegleria fowleri. Thus, our result shows, for the first time, that
      N. polaris can survive after 10 years of storage at 4  degrees C. This finding
      may help us understand the still undescribed effects of environmental samples on
      viability of amoebae.

PMID- 29380052
TI  - Immune challenges decrease biliverdin concentration in the spleen of northern
      Bobwhite quail, Colinus virginianus.
AB  - Most antioxidants have multiple functions; in addition to minimizing oxidative
      damage, many antioxidants have immune-modulating properties. For example,
      biliverdin is produced in the liver and spleen from the breakdown of heme, and
      has putative immune-suppressing and antioxidant properties. However, the majority
      of these properties have been investigated in vitro or in mammalian models, in
      which biliverdin reductase converts virtually all biliverdin to bilirubin. Thus,
      biliverdin's physiological roles remain largely untested. Here, we investigated
      whether biliverdin has immunomodulating roles by injecting Northern Bobwhite
      quail (Colinus virginianus) with either a vehicle control, lysed and rinsed pig
      red blood cells (pRBC) that contain erythrocyte antigens but no heme, or intact
      pRBC that contain both erythrocyte antigens and hemoglobin, thus increasing the
      amount of heme that can be converted to biliverdin. We then quantified
      hemagglutination and hemolysis ability, and biliverdin concentration in the liver
      and spleen, on 3, 6, and 9 days post-injection. We found that hemagglutination
      was greater in individuals that received intact pRBC, but not in those injected
      with heme-removed pRBC, demonstrating that biliverdin does not suppress immune
      function at this dosage. Biliverdin levels of liver and spleen were correlated
      within individuals, suggesting organism-level variation in biliverdin production.
      Lastly, individuals injected with intact pRBC had a reduced biliverdin
      concentration in the spleen, suggesting that immune challenges may reduce
      biliverdin production or accumulation. This initial investigation demonstrated
      that biliverdin may have more nuanced physiological roles than previously
      reported, supporting the value of further investigations into the physiology of
      biliverdin.

PMID- 29380053
TI  - Cardiovascular adjustments with egg temperature at 90% incubation in embryonic
      American alligators, Alligator mississippiensis.
AB  - American alligators (Alligator mississippiensis) deposit eggs in a mound nest,
      potentially subjecting embryos to daily variations in temperature. Whilst adult
      crocodilian cardiovascular responses to changes in temperature have been
      investigated, similar studies in alligator embryos are limited. We investigated
      cardiovascular function of embryonic alligators during heating and cooling as
      well as at different temperatures. We measured arterial blood pressure (Pm) and
      heart rate (fH) in response to cooling (30-26  degrees C), heating (26-36 
      degrees C), followed by a reciprocal cooling event (36-26  degrees C) and
      assessed the cardiac baroreflex at 30 and 36  degrees C. Embryonic fH increased
      during heating events and decreased during cooling events, while embryos were
      hypotensive at 26 and 36  degrees C, although Pm did not differ between heating
      or cooling events. There was a clear temperature-dependent heart rate hysteresis
      at a given embryo's temperature, depending on whether embryos were cooling or
      heating. Cardiovascular regulation through the cardiac limb of the baroreflex was
      not affected by temperature, despite previous studies suggesting that vagal tone
      is present at both low and high temperatures.

PMID- 29380054
TI  - Children's access to major hospitals estimated to provide pediatric inpatient
      services 24 h a day in Japan.
AB  - : To measure the geographic accessibility of pediatric inpatient medical services
      in Japan, the proportion of children who lived within 5, 10, 20, and 30 km of the
      nearest hospital providing inpatient services for children and staffed by at
      least five full-time equivalent pediatricians was calculated. Geographic
      information systems were used to assess the location of the hospitals, and the
      latitude, longitude, and child population of 219,100 residential "blocks" in
      Japan. The population and proportion of children in over- and under-populated
      prefectures were compared to show differences in accessibility. CONCLUSION: Of
      the 15.88 million children in Japan, 14.72 million (92.7%) lived within 30 km of
      the nearest hospital with at least five full-time equivalent pediatricians. They
      could therefore probably reach it within 1 h by car. However, the proportion of
      children living further than 30 km away varied across under- and over-populated
      prefecture groups. More than half of the 1.16 million children who lived in areas
      more than 30 km from the nearest hospital were in the 12 prefectures with the
      lowest population densities. Plans for medical provision for children should
      therefore be formulated differently for over- and under-populated prefectures,
      with provision made for improved transport from remote areas. What is Known: *
      The number of pediatricians and hospitals with pediatric departments is surveyed
      by Japanese health authorities, and the statistics on medical resources in each
      prefecture are published on the Japanese government's website. * Accessibility of
      medical services for children has not been well analyzed in Japan. What is New: *
      In total, 92.7% of Japanese children lived within 30 km of the nearest major
      hospital providing pediatric inpatient services. * More than half of the
      remaining children were residents of the 12 prefectures with the lowest
      population density.

PMID- 29380055
TI  - Signaling and metabolic properties of fast and slow smooth muscle types from
      mice.
AB  - This study aims to improve the classification of smooth muscle types to better
      understand their normal and pathological functional phenotypes. Four different
      smooth muscle tissues (aorta, muscular arteries, intestine, urinary bladder) with
      a 5-fold difference in maximal shortening velocity were obtained from mice and
      classified according to expression of the inserted myosin heavy chain (SMHC-B).
      Western blotting and quantitative PCR analyses were used to determine 15
      metabolic and 8 cell signaling key components in each tissue. The slow muscle
      type (aorta) with a 12 times lower SMHC-B had 6-fold lower expression of the
      phosphatase subunit MYPT1, a 7-fold higher expression of Rhokinase 1, and a 3
      fold higher expression of the PKC target CPI17, compared to the faster (urinary
      bladder) smooth muscle. The slow muscle had higher expression of components
      involved in glucose uptake and glycolysis (type 1 glucose transporter, 3 times;
      hexokinase, 13 times) and in gluconeogenesis (phosphoenolpyruvate carboxykinase,
      43 times), but lower expression of the metabolic sensing AMP-activated kinase,
      alpha 2 isoform (5 times). The slow type also had higher expression of enzymes
      involved in lipid metabolism (hormone-sensitive lipase, 10 times; lipoprotein
      lipase, 13 times; fatty acid synthase, 6 times; type 2 acetyl-coenzyme A
      carboxylase, 8 times). We present a refined division of smooth muscle into muscle
      types based on the analysis of contractile, metabolic, and signaling components.
      Slow compared to fast smooth muscle has a lower expression of the deactivating
      phosphatase and upregulated Ca2+ sensitizing pathways and is more adapted for
      sustained glucose and lipid metabolism.

PMID- 29380056
TI  - Endothelial-dependent dilation following chronic hypoxia involves TRPV4-mediated
      activation of endothelial BK channels.
AB  - Following chronic hypoxia (CH), the systemic vasculature exhibits blunted
      vasoconstriction due to endothelial-dependent hyperpolarization (EDH). Previous
      data demonstrate that subsequent to CH, EDH-mediated vasodilation switches from a
      reliance on SKca and IKca channels to activation of the endothelial BKca channels
      (eBK). The mechanism by which endothelial cell stimulation activates eBK channels
      following CH is not known. We hypothesized that following CH, EDH-dependent
      vasodilation involves a TRPV4-dependent activation of eBK channels. ACh induced
      concentration-dependent dilation in pressurized gracilis arteries from both
      normoxic and CH rats. Inhibition of TRPV4 (RN-1734) attenuated the ACh response
      in arteries from CH rats but had no effect in normoxic animals. In the presence
      of L-NNA and indomethacin, TRPV4 blockade attenuated ACh-induced vasodilation in
      arteries from CH rats. ACh elicited endothelial TRPV4-mediated Ca2+ events in
      arteries from both groups. GSK1016790A (GSK101, TRPV4 agonist) elicited
      vasodilation in arteries from normoxic and CH rats. In arteries from normoxic
      animals, TRAM-34/apamin abolished the dilation to TRPV4 activation, whereas
      luminal iberiotoxin had no effect. In CH rats, only administration of all three
      Kca channel inhibitors abolished the dilation to TRPV4 activation. Using
      Duolink(r), we observed co-localization between Cav-1, TRPV4, and BK channels in
      gracilis arteries and in RAECs. Disruption of endothelial caveolae with methyl
      beta-cyclodextrin significantly decreased ACh-induced vasodilation in arteries
      from both groups. In gracilis arteries, endothelial membrane cholesterol was
      significantly decreased following 48 h of CH. In conclusion, CH results in a
      functional coupling between muscarinic receptors, TRPV4 and Kca channels in
      gracilis arteries.

PMID- 29380057
TI  - Commentary on: Survival benefit of mantle cell lymphoma patients enrolled in
      clinical trials; a joint study from the LYSA group and French cancer registries.

PMID- 29380058
TI  - Patients' and hematologists' concerns regarding tyrosine kinase-inhibitor therapy
      in chronic myeloid leukemia.
AB  - PURPOSE: To explore patients' and hematologists' concerns regarding tyrosine
      kinaseinhibitor (TKI)-therapy and identify variables associated these concerns.
      Methods A cross-sectional questionnaire including 16 common issues related to TKI
      therapy was distributed to adults with chronic myeloid leukemia (CML) receiving
      TKIs and hematologists treating CML patients and answered anonymously. RESULTS:
      Data from 1518 patient respondents receiving TKI-therapy >= 3 months were
      analyzed. 939 (62%) were male. Median age was 42 years. 72% were receiving
      imatinib. Median TKI-therapy duration was 27 months. Data from 259 hematologist
      respondents were analyzable. 154 (59%) treated > 5 persons with CML per month.
      Median number of concerns was 5 (range 0-16) for both patients and hematologists.
      The top five issues for both cohorts were new drug development, stopping TKI
      therapy, TKI-reimbursement policies, TKI-related adverse effects and long-term
      efficacy of TKIs. 12 issues attracted proportionally discordant attention between
      patients and hematologists. Patients were more concerned with TKI-reimbursement
      policies, price reduction of TKIs, TKI-related adverse effects, restrictions to
      daily life, CML knowledge and interpretation of laboratory data, whereas
      hematologists were more concerned with stopping TKI-therapy, TKI choice,
      monitoring, TKI dose-adjustment, quality of generics and switching between
      branded and generic TKIs. In multivariate analyses female sex [OR = 1.4 (1.1
      1.7); p = 0.008], education level >= bachelor e[OR = 1.8 (1.4-2.2); p < 0.001],
      TKI-therapy duration 36-< 60 months [OR = 1.4 (1.0-1.9); p = 0.049] and having
      adverse impact on daily life and work [OR = 1.5 (1.2-1.8]; p = 0.001] were
      associated with greater numbers of patients' concerns. CONCLUSIONS: Our data
      suggested hematologists need to be aware of CML patients' concerns to improve
      their quality-of-life and patient-hematologist communication.

PMID- 29380059
TI  - Post-transplantation Development of Food Allergies.
AB  - PURPOSE OF REVIEW: The development of food allergies is increasingly being
      recognized as a post-solid organ transplant complication. In this article, we
      review the spectrum of post-transplant food allergy development and the proposed
      mechanisms for de novo food allergies and the clinical significance they pose.
      RECENT FINDINGS: The development of new food allergies is disproportionately
      associated with pediatric liver transplants, where it occurs in up to 38% of
      select populations. The mechanism of food allergy development is not completely
      understood; however, it is likely promoted by unbalanced immune suppression. De
      novo food allergy development is a common complication of solid organ transplants
      with the highest risk occurring in pediatric liver transplant recipients. There
      are likely multiple mechanisms for food allergy development including passive
      transfer of membrane-bound IgE and lymphocytes from donor to recipient, as well
      as loss of food tolerance and active development of new food allergies. The
      optimal management of food allergies following organ transplants has not been
      well researched but may include changing the immune suppression regimen if the
      food allergy does not resolve without intervention.

PMID- 29380060
TI  - Serum levels of a cell death biomarker predict the development of cirrhosis
      related conditions in primary biliary cholangitis.
AB  - Non-invasive predictors for the development of cirrhosis-related conditions are
      needed for patients with primary biliary cholangitis (PBC). We investigated the
      association between cytokeratin-18 fragments (M30 and M65) and liver histology,
      treatment response and the development of cirrhosis-related conditions in
      patients with PBC. We retrospectively reviewed the clinical data of 111
      individuals with biopsy-proven PBC. Serum M30 and M65 levels were measured using
      stored sera. M30 were significantly decreased after treatment, but there was no
      significant change in the M65 levels. M65 was significantly higher in non
      responders according to the Paris-I and Paris-II definitions. In the multivariate
      analysis, high levels of M65 were significantly associated with advanced Scheuer
      stage (odds ratio 5.86; 95% confidence interval 0.55-22.2; P = 0.009) and with
      the development of cirrhosis-related conditions (hazard ratio 3.94; 95%
      confidence interval: 1.06-14.5, P = 0.039). Among PBC patients without cirrhosis,
      those with high serum M65 levels at baseline were at higher risk of developing
      cirrhosis-related conditions (log-rank test; P = 0.001). High levels of serum M65
      may be a non-invasive and early predictor of the development of cirrhosis-related
      conditions in PBC patients. Our findings may help initiate therapies earlier for
      those at risk for cirrhosis.

PMID- 29380061
TI  - Hepatic stellate cells derived from the nestin-positive cells in septum
      transversum during rat liver development.
AB  - Hepatic stellate cells (HSCs) play a principal role in Vitamin A metabolism and
      are considered the major matrix-producing cell type in the diseased liver. Rat
      HSCs are identified by immunohistochemistry with myogenic or mesenchymal (desmin,
      vimentin, and alpha-smooth muscle actin) or neural (e.g., GFAP or neuronal cell
      adhesion molecule) markers. Embryonic origin of rat HSCs was determined using
      these markers. Nestin, an intermediate filament protein originally identified in
      neuronal stem or progenitor cells, is widely used as a stem cell marker,
      including hepatic stem cells in adult rat livers. Additionally, nestin is
      reportedly expressed in activated HSCs during liver injury and hepatic
      regeneration. However, little is known about nestin expression in rat fetal liver
      HSCs. The present study aimed to clarify nestin-positive HSC expression during
      rat liver development. At embryonic day (ED) 10.5, nestin expression in
      mesenchymal cells adjacent to the liver bud was detected by immunohistochemistry.
      At ED 11.5, nestin-positive cells were also detected in desmin-positive cells
      appearing and increasing in intensity by ED 16.5. However, nestin-positive cells
      in the parenchyma decreased by ED 20.5 or later. These findings reveal that the
      nestin-positive HSCs during rat liver development originate from nestin-positive
      mesenchymal cells in the septum transversum.

PMID- 29380063
TI  - Intraoperative monitoring of cerebral cortical blood flow and middle cerebral
      artery pressure as a substitute for preoperative balloon test occlusion in
      patients with internal carotid artery aneurysms.
AB  - BACKGROUND: Balloon test occlusion (BTO) is a useful examination to evaluate the
      indications and methods for revascularization when treating unclippable internal
      carotid artery (ICA) aneurysms by parent artery occlusion. The purpose of the
      present study was to investigate the relationship between intraoperative
      monitoring of cerebral cortical blood flow (CoBF) and middle cerebral artery
      (MCA) pressure during surgical parent artery occlusion and the findings of BTO.
      METHODS: Eleven patients with an ICA aneurysm in the cavernous portion underwent
      preoperative BTO with brain perfusion single-photon emission tomography. CoBF was
      monitored intraoperatively in all patients using a laser Doppler probe. The
      lowest CoBF during test occlusion of the ICA under functioning superficial
      temporal artery-middle cerebral artery (STA-MCA) bypass was determined, and the
      ratio of the value to the CoBF immediately before test occlusion of the ICA was
      calculated in the frontal and temporal lobes. When the CoBF ratio in the frontal
      or temporal lobe was less than 0.9, high-flow bypass grafting was added. The MCA
      pressure was also measured by temporarily occluding the proximal STA. RESULTS: Of
      the 11 patients undergoing STA-MCA bypass, 5 patients underwent concomitant high
      flow bypass grafting. Significant differences in the cerebrovascular reserve
      based on SPECT during BTO, CoBF, and the MCA pressure ratio during surgery were
      observed when comparing the two groups. CONCLUSIONS: Intraoperative monitoring of
      CoBF and MCA pressure may be useful, along with preoperative BTO, for patients
      with unclippable ICA aneurysms.

PMID- 29380062
TI  - The profiling of plasma free amino acids and the relationship between serum
      albumin and plasma-branched chain amino acids in chronic liver disease: a single
      center retrospective study.
AB  - BACKGROUND: It is poorly understood how an imbalance of plasma-free amino acids
      (PFAAs) occurs and how the imbalance shows an association with the serum albumin
      (sAlb) level during the progression of chronic liver disease (CLDs). The aim of
      this study is to elucidate the profiles of PFAAs and the relationship between
      sAlb and PFAAs in recent patients with CLDs during the progression. METHODS: We
      retrospectively evaluated the 1569 data of PFAAs data obtained from 908 patients
      with various CLDs (CHC, CHB. alcoholic, NAFLD/NASH, PBC, AIH, PSC, and
      cryptogenic). In total, 1140 data of PFAAs could be analyzed in patients with
      CLDs dependent of their Child-Pugh (CP) score. RESULTS: Various imbalances in
      PFAAs were observed in each CLDs during the progression. Univariate and
      multivariate analysis revealed that among 24 PFAAs, the level of plasma-branched
      chain amino acids (pBCAAs) was significantly associated with the CP score,
      especially the sAlb score, in patients with chronic hepatitis C virus (CHC),
      NAFLD/NASH and PBC. The correlation coefficient values between sAlb and pBCAAs-to
      Tyrosine ratio (BTR) in these patients were 0.53, 0.53 and 0.79, respectively.
      Interestingly, although the pBCAAs in NAFLD/NASH patients varied even when the
      sAlb was within the normal range, the pBCAAs tended to be low when the sAlb was
      below the normal range. CONCLUSIONS: Although a decrease in the level of pBCAAs
      was observed during the progression regardless of the CLD etiology, the level of
      total pBCAAs was independently associated with the sAlb level in the PFAAs of
      CHC, PBC and NAFLD/NASH. The correlation between sAlb and BTR showed the highest
      value in PBC patients among the patients with CLDs. A decrease in pBCAAs often
      occurred in NASH even when the sAlb level was kept in the normal range.

PMID- 29380064
TI  - The complete nucleotide sequence and genome organisation of a novel member of the
      family Betaflexiviridae from Actinidia chinensis.
AB  - We report the complete genome sequence of a novel virus, tentatively named
      "actinidia seed-borne latent virus" (ASbLV), isolated from Actinidia chinensis in
      Auckland, New Zealand. The complete genome of ASbLV is 8,192 nucleotides long,
      excluding the 3' poly(A) tail, contains four open reading frames, and is most
      closely related to Caucasus prunus virus (56% nucleotide sequence identity), a
      member of the genus Prunevirus. Based on the demarcation criteria of the family
      Betaflexiviridae, ASbLV is a new member of the genus Prunevirus.

PMID- 29380065
TI  - A single surgeon's experience transitioning to robotic-assisted right colectomy
      with intracorporeal anastomosis.
AB  - BACKGROUND: Despite substantial evidence demonstrating benefits of minimally
      invasive surgery, a large percentage of right colectomies are still performed via
      an open technique. Most laparoscopic right colectomies are completed as a hybrid
      procedure with extracorporeal anastomosis. As part of a pure minimally invasive
      procedure, intracorporeal anastomosis (ICA) may confer additional benefits for
      patients. The robotic platform may shorten the learning curve for minimally
      invasive right colectomy with ICA. METHODS: From January 2014 to May 2016, 49
      patients underwent robotic-assisted right colectomy by a board-certified
      colorectal surgeon (S.R). Extracorporeal anastomosis (ECA) was used in the first
      20 procedures, whereas ICA was used in all subsequent procedures. Outcomes
      recorded in a database for retrospective review included operating time (OT),
      estimated blood loss (EBL), length of stay (LOS), conversion rate, complications,
      readmissions, and mortality rate. RESULTS: Comparison of average OT, EBL, and LOS
      between extracorporeal and intracorporeal groups demonstrated no significant
      differences. For all patients, average OT was 141.6 +/- 25.8 (range 86-192) min,
      average EBL was 59.5 +/- 83.3 (range 0-500) mL, and average LOS was 3.4 +/- 1.19
      (range 1.5-8) days. Four patients required conversion, all of which occurred in
      the extracorporeal group. There were no conversions after the 18th procedure. The
      60-day mortality rate was 0%. There were no anastomotic leaks, ostomies created,
      or readmissions. As the surgeon gained experience, a statistically significant
      increase in lymph node sampling was observed in oncologic cases (p = .02).
      CONCLUSIONS: The robotic platform may help more surgeons safely and efficiently
      transition to a purely minimally invasive procedure, enabling more patients to
      reap the benefits of less invasive surgery. Transitioning from ECA to ICA during
      robotic right colectomy resulted in no significant change in OT or LOS. A lower
      rate of conversion to open surgery was noted with increased experience.

PMID- 29380066
TI  - Outcomes and quality of life assessment after per oral endoscopic myotomy (POEM)
      performed in the endoscopy unit with trainees.
AB  - BACKGROUND: Per oral endoscopic myotomy (POEM) has emerged as a promising option
      for the treatment of achalasia. This study assessed POEM training process,
      outcomes, and improvement in quality of life after POEM performed by an
      interventional endoscopist (mentor) with trainees. METHODS: We performed a
      retrospective review of data for patients who underwent POEM with involvement of
      trainees. Trainees were trained in performing mucosotomy, submucosal dissection,
      creating submucosal tunnel, identifying gastroesophageal junction, myotomy, and
      closure of mucosal incision in a step-by-step fashion. Trainees' performance on
      each step was evaluated by the mentor based on several key points in each step.
      The short form 36 (SF36) was obtained before and certain times after the primary
      POEM procedure was performed. RESULTS: Sixty-two patients, 26 males and 36
      females with a mean age of 59 years, who underwent POEM were enrolled. A
      checklist included all related items for each step was established. All trainees
      obtained competence within 6 cases for each step. 61/62 (98.3%) patients had a
      significant improvement in the Eckardt's score post POEM: 9.3 +/- 1.5 prior to
      POEM and 2.6 +/- 1.2 after the POEM (P = 0.001) and a decrease in mean lower
      esophageal sphincter pressure (LES): pre- and post-procedure mean LES pressures
      were 28.5 +/- 11.4 and 12.1 +/- 4.5 mmHg, respectively (P = 0.001). The SF-36
      questionnaire demonstrated a significant improvement in quality of life and
      comparable with those without trainees in other studies. CONCLUSION: This
      preliminary study showed for the first time that training for POEM can be
      performed in a step-by-step fashion, learning mucosal incision, submucosal
      dissection, myotomy, and mucosal incision closure from an expert interventional
      endoscopist without increasing adverse events. The checklist for each step could
      be used as an important guide in training POEM. The outcomes of POEM in this
      study were similar to those reported by others without trainees. Further multiple
      center studies are needed to verify this training process and to establish a
      formal training protocol.

PMID- 29380067
TI  - A new system of computer-assisted navigation leading to reduction in operating
      time in uncemented total hip replacement in a matched population.
AB  - Computer-assisted navigation techniques are used to optimise component placement
      and alignment in total hip replacement. It has developed in the last 10 years but
      despite its advantages only 0.3% of all total hip replacements in England and
      Wales are done using computer navigation. One of the reasons for this is that
      computer-assisted technology increases operative time. A new method of pelvic
      registration has been developed without the need to register the anterior pelvic
      plane (BrainLab hip 6.0) which has shown to improve the accuracy of THR. The
      purpose of this study was to find out if the new method reduces the operating
      time. This was a retrospective analysis of comparing operating time in computer
      navigated primary uncemented total hip replacement using two methods of
      registration. Group 1 included 128 cases that were performed using BrainLab
      versions 2.1-5.1. This version relied on the acquisition of the anterior pelvic
      plane for registration. Group 2 included 128 cases that were performed using the
      newest navigation software, BrainLab hip 6.0 (registration possible with the
      patient in the lateral decubitus position). The operating time was 65.79 (40-98)
      minutes using the old method of registration and was 50.87 (33-74) minutes using
      the new method of registration. This difference was statistically significant.
      The body mass index (BMI) was comparable in both groups. The study supports the
      use of new method of registration in improving the operating time in computer
      navigated primary uncemented total hip replacements.

PMID- 29380068
TI  - Impedance Oscillometry: Emerging Role in the Management of Chronic Respiratory
      Disease.
AB  - PURPOSE OF REVIEW: Chronic respiratory diseases affecting adults and children are
      widely prevalent, so lung function testing is imperative for diagnosis and
      management. Spirometry is the traditional standard measure of lung function;
      however, certain groups of patients are unable to provide accurate and
      reproducible exhalation maneuvers. Consequently, the impedance oscillometry
      system (IOS) has been developed as an effort, independent technique to assess
      airway function in children and the elderly. To better understand this emerging
      modality, the following review will compare IOS with spirometry, examine the
      function of the device, provide interpretation strategies, and discuss the
      evidence supporting its use in adults and children with chronic lung disease.
      RECENT FINDINGS: In a population of symptomatic adults with suspected COPD,
      impedance oscillometry resistance measurements correlate with FEV1 and lung
      resistance increases with the severity of airflow limitation. In patients with
      asthma, IOS is a sensitive measure of airway hyperresponsiveness and
      bronchodilator response. Impedance oscillometry is evolving as an alternative
      measure to assess lung function pediatric and adult populations.

PMID- 29380070
TI  - Publisher Correction: Evaluation of the level of dynamic thiol/disulphide
      homeostasis in adolescent patients with newly diagnosed primary hypertension.
AB  - Owing to an error in typesetting, the name of the author Atilla Halil Elhan was
      rendered wrongly. The original publication has now been corrected in this
      respect.

PMID- 29380069
TI  - Emotion regulation difficulties in traumatized youth: a meta-analysis and
      conceptual review.
AB  - This article provides a quantitative and conceptual review of emotion regulation
      difficulties in trauma-exposed young people, and informs future directions in the
      field. Despite long-standing interest in the influence of emotion regulation
      difficulties on different internalizing and externalizing psychiatric disorders
      in childhood, several questions remain unresolved with respect to children and
      adolescents with PTSD (post-traumatic stress disorder). Meta-analytic data from
      adult victims suggest that emotion regulation problems are associated with PTSD,
      but this has never been studied in children and young people. We therefore
      provide a conceptual review of features related to the phenomenology, assessment,
      severity and treatment of emotion regulation difficulties in trauma-exposed
      children and young people. We combine this with a meta-analysis of published
      literature. We searched studies in Medline, PsychINFO, and Embase databases based
      on pre-selected criteria. Eight hundred and eighty-six papers were identified and
      41 were included. We found that children and adolescents with a diagnosis of PTSD
      reported more emotion regulation difficulties than those who did not develop
      PTSD, and that the overall association between the two symptom dimensions was
      moderately strong. We identify a number of research priorities: the development
      of instruments to assess emotion regulation difficulties in children, the design
      of studies that describe its prevalence in young epidemiological traumatized
      samples, its predictive role in the onset, severity and persistence of post
      traumatic symptoms, and its relevance as a moderator, outcome or treatment target
      for young survivors.

PMID- 29380071
TI  - Programmed cell death in wheat (Triticum aestivum L.) endosperm cells is affected
      by drought stress.
AB  - Drought frequently occurs during wheat (Triticum aestivum L.) grain filling. The
      objectives of this study were (i) to investigate the effect of post-anthesis
      drought on programmed cell death (PCD) in wheat endosperm cells and (ii) to
      examine the role of ethylene (ETH) receptors and abscisic acid (ABA) in
      regulating wheat endosperm PCD. Two winter wheat cultivars ('Xindong 18' and
      'Xindong 22') were used in this study. Grain samples were collected from normal
      and drought stressed plants at 5-day intervals between 5 and 35 days post
      anthesis. The samples were then compared with respect to cell viability, nuclear
      morphometry, cell ultrastructure, DNA integrity, nucleic acid content, and
      nuclease activity. Analysis was also conducted about gene transcripts related to
      PCD, ETH receptors, and ABA biosynthesis and degradation. Drought stress reduced
      cell viability, accelerated nuclear deformation, and increased mitochondrial
      dissolution. The activity of nucleic acid hydrolase was greater, and the nucleic
      acid concentrations were less in the drought treatments than in the control. As a
      result, the peak in DNA fragmentation occurred earlier in the drought treatment.
      Drought stress significantly increased the expression of four genes related to
      ABA (nced1, nced2, ao1, ao2). In contrast, drought significantly reduced the
      expression of four genes related to ETH receptors (ers1, ers2 etr1, etr2) and one
      gene related to PCD (dad1). In summary, the results indicated that drought stress
      caused PCD to occur earlier in the endosperm of winter wheat.

PMID- 29380072
TI  - Sleep Disturbance and Cognitive Dysfunction in Multiple Sclerosis: a Systematic
      Review.
AB  - PURPOSE OF REVIEW: The present review summarizes recent research on the
      association between sleep disturbance and cognitive dysfunction in MS. Assessment
      methodology, domain-specific associations between sleep disturbance and cognitive
      dysfunction, and implications for future research and treatment are discussed.
      RECENT FINDINGS: All 12 studies included in this review found significant
      associations between sleep disturbance and cognitive dysfunction; however,
      results varied considerably depending on the assessment method used and the
      cognitive domain assessed. Self-reported sleep disturbance generally predicted
      self-report but not objective measures of cognitive dysfunction. Objective sleep
      measures (e.g., polysomnography, actigraphy) generally predicted objective
      impairments in processing speed and attention; however, objective sleep
      disturbance was more variable in predicting performance in other cognitive
      domains (e.g., memory, executive function). Sleep disturbance may help predict
      future cognitive decline in MS. Results highlight the need to integrate sleep
      assessment into routine MS care. Interventions aimed treating sleep disturbance
      may offer promise for improving cognitive dysfunction in MS.

PMID- 29380073
TI  - Threshold response and bistability in gene regulation by small noncoding RNA.
AB  - In this paper, we study through mathematical modelling the combined effect of
      transcriptional and translational regulation by proteins and small noncoding RNAs
      (sRNA) in a genetic feedback motif that has an important role in the survival of
      E. coli under stress associated with oxygen and energy availability. We show that
      subtle changes in this motif can bring in drastically different effects on the
      gene expression. In particular, we show that a threshold response in the gene
      expression changes to a bistable response as the regulation on sRNA synthesis or
      degradation is altered. These results are obtained under deterministic
      conditions. Next, we study how the gene expression is altered by additive and
      multiplicative noise which might arise due to probabilistic occurrences of
      different biochemical events. Using the Fokker-Planck formulation, we obtain
      steady-state probability distributions for sRNA concentration for the network
      motifs displaying bistability. The probability distributions are found to be
      bimodal with two peaks at low and high concentrations of sRNAs. We further study
      the variations in the probability distributions under different values of noise
      strength and correlations. The results presented here might be of interest for
      designing synthetic network for artificial control.

PMID- 29380074
TI  - Surface Enrichment and Depletion of the Active Ingredient in Spray Dried
      Amorphous Solid Dispersions.
AB  - PURPOSE: To study the effects of physicochemical properties of drug and polymer,
      as well as the drug-polymer interactions, on the surface composition of SDDs.
      METHODS: Ethanol solutions containing a model drug (IMC, NMP or FCZ) and a model
      polymer (PVPK12, PVPK30 or PVP-VA) were spray dried, and the surface composition
      of SDDs was analyzed by XPS. The surface tensions of pure components and their
      solutions were measured using Wilhelmy plate and/or calculated using ACD/Labs.
      NMR and DLS were used to obtain the diffusion coefficients of IMC, NMP, PVPK12
      and PVPK30 in solvents. Flory-Huggins interaction parameters for selected drug
      polymer pairs were obtained using a melting point depression method. RESULTS:
      Significant surface enrichment or depletion of the drug was observed in SDDs
      depending on the particular drug-polymer combination. With PVP as the dispersion
      polymer, IMC and NMP were surface enriched; whereas FCZ, a hydrophilic drug, was
      surface depleted. With increasing PVP molecular weight, the surface drug
      concentration increased, and the effect was greater in the NMP/PVP and FCZ/PVP
      systems than in the IMC/PVP system where strong drug-polymer interaction existed.
      Changing the polymer from PVP to PVP-VA reduced the surface concentration of the
      drug. CONCLUSIONS: The surface concentration of a SDD can be significantly
      different from the bulk concentration. The main results of this work are
      consistent with the notion that the relative surface tensions control surface
      enrichment or depletion. Besides, the relative diffusion rates of the components
      and the strength of their interactions may also affect the surface composition of
      the SDDs.

PMID- 29380075
TI  - Effect of escitalopram and carbidopa on bone markers in Wistar rats: a
      preliminary experimental study.
AB  - In view of the opposite effects of gut and brain serotonin in bone, the key role
      of Wnt beta/catenin pathway in osteoblastic proliferation and the controversial
      bony effects of selective serotonin reuptake inhibitors antidepressants, the
      present study investigated the effects of escitalopram alone and in combination
      with carbidopa (to block gut-derived serotonin) on markers of bone turnover and
      Wnt signaling and micro-CT in male Wistar rats. Escitalopram (2.0 mg/kg, p.o.)
      and carbidopa (10 mg/kg, p.o.) were administered daily for 40 days following
      which indicators of reduced (dickkopf-1, sclerostin), and increased (alkaline
      phosphatase) bone formation and bone resorption markers (receptor activator of
      nuclear factor kappaB ligand, tartrate-resistant acid phosphatase 5b) were
      determined. Our results indicated that escitalopram adversely affected bone as
      indicated by reduced bone formation and enhanced bone resorption. Further, the
      effects of escitalopram on bone formation were possibly mediated through gut
      serotonin while the mechanisms responsible for effects on resorption seem
      unrelated to gut serotonin. The promising effects of carbidopa on bone formation,
      as observed in our study, open up exciting possibilities for this drug requiring
      further investigations.

PMID- 29380076
TI  - Effect of Microenvironmental pH Modulation on the Dissolution Rate and Oral
      Absorption of the Salt of a Weak Acid - Case Study of GDC-0810.
AB  - PURPOSE: The purpose of this work is to investigate the effect of
      microenvironmental pH modulation on the in vitro dissolution rate and oral
      absorption of GDC-0810, an oral anti-cancer drug, in human. METHODS: The pH
      solubility profile of GDC-0810 free acid and pHmax of its N-Methyl-D-glucamine
      (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG
      salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations
      containing different levels of sodium bicarbonate as the pH modifier were tested
      for dissolution under the dual pH-dilution scheme. Three tablet formulations were
      evaluated in human as a part of a relative bioavailability study. A 200-mg dose
      of GDC-0810 was administered QD with low fat food. RESULTS: Intrinsic solubility
      of GDC-0810 free acid was found to be extremely low. The pHmax of the NMG salt
      suggested a strong tendency for form conversion to the free acid under GI
      conditions. In vitro dissolution profiles showed that the dissolution rate and
      extent of GDC-0810 increased with increasing the level of sodium bicarbonate in
      the formulation. The human PK data showed a similar trend for the geometric mean
      of Cmax and AUC0-t for formulations containing 5%, 10%, and 15% sodium
      bicarbonate, but the difference is not statistically significant. CONCLUSION:
      Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt
      tablet formulations enhanced in vitro dissolution rate of GDC-0810 via
      microenvironmental pH modulation. The human PK data showed no statistically
      significant difference in drug exposure from tablets containing 5%, 10%, and 15%
      sodium bicarbonate.

PMID- 29380078
TI  - Thermophysical properties of nanofluids.
AB  - This paper discusses the current state of knowledge of the thermophysical
      properties of nanofluids. The viscosity, thermal conductivity and heat transfer
      of nanofluids are considered. Experimental and molecular dynamics data are
      presented. It is shown that viscosity and thermal conductivity of nanofluids
      generally cannot be described by classical theories. The transport coefficients
      of nanofluids depend not only on the volume concentration of the particles but
      also on their size and material. The viscosity increases with decreasing the
      particle size while the thermal conductivity increases with increasing the
      particle size. The reasons for this behavior are discussed. The heat transfer
      coefficient is determined by the nanofluid flow mode (laminar or turbulent). The
      use of the nanofluids as a coolant significantly affects the magnitude of the
      heat transfer coefficient. In laminar flow the heat transfer coefficient of
      nanofluids in all cases is much more than that of base fluids. It is shown that a
      2%-nanofluid intensifies the heat exchange more than twice compared to water. The
      effect of using nanofluids in turbulent mode depends not only on the thermal
      conductivity of the nanofluid, but also on its viscosity.

PMID- 29380077
TI  - Brevibacillus parabrevis MTCC 12105: a potential bacterium for pulp and paper
      effluent degradation.
AB  - A gram positive, rod shaped, bacterium was isolated from pulp and paper mill
      sludge and characterized as Brevibacillus parabrevis (MTCC 12105) by biochemical
      tests and 16S rRNA gene sequencing. CD and EOP stage wastewater, collected from a
      leading pulp and paper mill situated in North India, was used for degradation
      study. Wastewater degradation efficiency of the bacterial isolate was evaluated
      by Flask study in batch mode and Reactor study in semi continuous mode. The
      isolated bacterium showed a considerable reduction of the colour (59%), chemical
      oxygen demand (62%) and lignin (53.8%) content of Kraft paper mill effluent at 37
      degrees C after 5 days. During reactor study it reduced 42.6% Lignin, 51.6%
      Colour and 60.3% COD (chemical oxygen demand) of the wastewater at 48 h RT
      (retention time). The isolate was deposited at MTCC Chandigarh, India with an
      accession no. MTCC 12105.

PMID- 29380079
TI  - Machine Learning EEG to Predict Cognitive Functioning and Processing Speed Over a
      2-Year Period in Multiple Sclerosis Patients and Controls.
AB  - Event-related potentials (ERPs) show promise to be objective indicators of
      cognitive functioning. The aim of the study was to examine if ERPs recorded
      during an oddball task would predict cognitive functioning and information
      processing speed in Multiple Sclerosis (MS) patients and controls at the
      individual level. Seventy-eight participants (35 MS patients, 43 healthy age
      matched controls) completed visual and auditory 2- and 3-stimulus oddball tasks
      with 128-channel EEG, and a neuropsychological battery, at baseline (month 0) and
      at Months 13 and 26. ERPs from 0 to 700 ms and across the whole scalp were
      transformed into 1728 individual spatio-temporal datapoints per participant. A
      machine learning method that included penalized linear regression used the entire
      spatio-temporal ERP to predict composite scores of both cognitive functioning and
      processing speed at baseline (month 0), and months 13 and 26. The results showed
      ERPs during the visual oddball tasks could predict cognitive functioning and
      information processing speed at baseline and a year later in a sample of MS
      patients and healthy controls. In contrast, ERPs during auditory tasks were not
      predictive of cognitive performance. These objective neurophysiological
      indicators of cognitive functioning and processing speed, and machine learning
      methods that can interrogate high-dimensional data, show promise in outcome
      prediction.

PMID- 29380080
TI  - Reliability of respiratory pressure measurements in ventilated and non-ventilated
      patients in ICU: an observational study.
AB  - BACKGROUND: Assessment of maximum respiratory pressures is a common practice in
      intensive care because it can predict the success of weaning from ventilation.
      However, the reliability of measurements through an intubation catheter has not
      been compared with standard measurements. The aim of this study was to compare
      maximum respiratory pressures measured through an intubation catheter with the
      same measurements using a standard mouthpiece in extubated patients. METHODS: A
      prospective observational study was carried out in adults who had been under
      ventilation for at least 24 h and for whom extubation was planned. Maximal
      respiratory pressure measurements were carried out before and 24 h following
      extubation. RESULTS: Ninety patients were included in the analyses (median age:
      61.5 years, median SAPS2 score: 42.5 and median duration of ventilation: 7 days).
      Maximum respiratory pressures measured through the intubation catheter were as
      reliable as measurements through a standard mouthpiece (difference in maximal
      inspiratory pressure: mean bias = - 2.43 +/- 14.43 cmH2O and difference in
      maximal expiratory pressure: mean bias = 1.54 +/- 23.2 cmH2O). CONCLUSION:
      Maximum respiratory pressures measured through an intubation catheter were
      reliable and similar to standard measures. Clinical trial registration
      Retrospectively Registered in ClinicalTrials.gov (NCT02363231).

PMID- 29380081
TI  - Visualization of Endoplasmic Reticulum and Mitochondria in Aurantiochytrium
      limacinum by the Expression of EGFP with Cell Organelle-Specific
      Targeting/Retaining Signals.
AB  - Thraustochytrids are single cell marine eukaryotes that produce large amounts of
      polyunsaturated fatty acids such as docosahexaenoic acid. In the present study,
      we report the visualization of endoplasmic reticulum (ER) and mitochondria in a
      type strain of the thraustochytrid, Aurantiochytrium limacinum ATCC MYA-1381,
      using the enhanced green fluorescent protein (EGFP) with specific
      targeting/retaining signals. We expressed the egfp gene with ER
      targeting/retaining signals from A. limacinum calreticulin or BiP/GRP78 in the
      thraustochytrid, resulting in the distribution of EGFP signals at the perinuclear
      region and near lipid droplets. ER-TrackerTM Red, an authentic fluorescent probe
      for the visualization of ER in mammalian cells, also stained the same region. We
      observed small lipid droplets generated from the visualized ER in the early
      growth phase of cell culture. Expression of the egfp gene with the mitochondria
      targeting signal from A. limacinum cytochrome c oxidase resulted in the
      localization of EGFP near the plasma membrane. The distribution of EGFP signals
      coincided with that of MitoTracker(r) Red CMXRos, which is used to visualize
      mitochondria in eukaryotes. The ER and mitochondria of A. limacinum were
      visualized for the first time by EGFP with thraustochytrid cell organelle
      specific targeting/retaining signals. These results will contribute to
      classification of the intracellular localization of proteins expressed in ER and
      mitochondria as well as analyses of these cell organelles in thraustochytrids.

PMID- 29380082
TI  - Optimizing the flow adjustment of constituent concentrations via LOESS for trend
      analysis.
AB  - Trend analysis of stream constituent concentrations requires adjustment for
      exogenous variables like discharge because concentrations often have variable
      relations with flow. To remove the influence of flow on stream water quality
      data, an accurate characterization of the relationship between the constituent
      and streamflow is needed. One popular method, locally weighted regression
      (LOESS), provides an effective means for flow-adjusting concentrations. The LOESS
      fit can be tailored to the data via the smoothing parameter (f), so that the user
      can avoid overfitting or oversmoothing the data. However, it is a common practice
      to use a single f value when flow-adjusting water quality data for trend
      analysis. This study provides a robust, automated method for determining the
      optimal f value (fopt) for each dataset via an iterative K-fold cross-validation
      procedure that minimizes prediction error in LOESS. The method is developed by
      analyzing datasets of seven different constituents across 17 sites (119 datasets
      total) from a stream monitoring program in northwest Arkansas (USA). We recommend
      using 10 iterations of 10-fold cross-validation (10 * 10 CV) in order to select
      fopt when flow-adjusting water quality data with LOESS. The use of a default f
      value did not produce different trend interpretations for the data used here;
      however, the proposed approach may be helpful in other water quality studies
      which employ similar statistical fitting methods. Additionally, we provide an
      implementation of the method in the R statistical computing environment.

PMID- 29380083
TI  - Case series about ex vivo identification of squamous cell carcinomas by laser
      induced autofluorescence and Fourier transform infrared spectroscopy.
AB  - An ex vivo case series aimed at identification of normal laryngeal tissue from
      laryngeal epidermoid squamous keratinized carcinoma by measuring laser-induced
      autofluorescence (LIAF) and Fourier transform infrared-attenuated total
      reflectance (FTIR-ATR) spectra is presented. The case series results were
      obtained for paired samples extracted from three patients (exclusion: macroscopic
      changes of normal vocal cord observed during surgery; surgical intervention on
      vocal cord, treated only with chemotherapy or radiotherapy for carcinoma;
      inclusion: men, aged 57-68, non-smokers). For LIAF analysis, a 375-nm picosecond
      pulsed laser diode with 31 MHz pulse repetition rate, 100 ps full-time width at
      half-maximum, and average power 0.49 MUW was used. LIAF and FTIR-ATR spectra show
      noticeable differences between normal and malignant tissues. LIAF spectra
      differed in shape of emitted band, peak position, and band relative intensity of
      the two kinds of samples, evidencing hypsochromic shift and mean fluorescence
      intensity decrease of (75.42 +/- 3)% in malignant tissue with respect to the
      normal one. The lack of 1745 cm-1 band in FTIR-ATR spectra for malignant tissues
      could be considered an important indicative of the presence of this kind of
      tissue; moreover, it resulted a greater contribution of lipids and proteins in
      normal tissue and of collagen in malignant tissue. Penetration depth of the
      evanescent wave was about 2 MUm at an angle of 42 degrees . The two spectroscopic
      methods are complementary, are applicable for real-time measurements, and may
      enhance cancer detection and diagnostics. Results presented in this study
      evidence the potential of the two methods for future in vivo studies.

PMID- 29380084
TI  - Postgraduate education in dental implantology in the United Kingdom: a review.
AB  - BACKGROUND: The qualified dentists in the United Kingdom (UK) are not expected to
      be competent in practising implant dentistry without further training in the
      subject and there is now greater emphasis on postgraduate training in Dental
      Implantology. There are three main education pathways at present, yet their
      training standards vary significantly. This study aims to identify UK
      postgraduate academic qualifications and continuing professional development
      (CPD) courses available in the field of Dental Implantology and evaluates the
      current standard of the postgraduate training programmes against the Training
      Standards in Implant Dentistry (TSID) guidelines from Faculty of General Dental
      Practice (FGDP (UK)). RESULTS: There were eight master level courses with varying
      types of qualification and study mode. The mean duration and tuition fee of the
      courses were 2.50 years and L23,635.50 per course, respectively. There were eight
      postgraduate diploma part-time courses with the mean duration of 2.00 years, and
      the mean tuition fee of L20,177.08 per course. The mean duration for two
      postgraduate certificate part-time courses was 1.00 year with the mean tuition
      fee of L9441.50. However, there were no full-time study options for these
      courses. All courses identified stated their compliance with TSID guidelines. The
      mean duration for 13 CPD courses identified was 0.94 years and all courses were
      delivered in a part-time mode. Eleven of these courses were verifiable CPD
      courses, and two courses were providing certificates only. Not all courses were
      fully compliant with TSID guidelines. Ten courses clearly stated that they
      provide mentoring for implant placements, and the number of supervised cases
      varied considerably between 1 and 50. CONCLUSION: Development of FGDP (UK) TSID
      guidelines has led to a significant improvement in the quality of postgraduate
      education in Dental Implantology in the UK. However, not all courses are fully
      compliant with these guidelines and the provision of mentoring for implant
      placements also needs to be standardised. Quality-assured training is directly
      related to patient safety, and therefore all UK postgraduate training pathways
      must ensure their compliance with the current guidelines.

PMID- 29380085
TI  - Current perspectives on bone metastases in castrate-resistant prostate cancer.
AB  - Prostate cancer is the most frequent noncutaneous cancer occurring in men. On
      average, men with localized prostate cancer have a high 10-year survival rate,
      and many can be cured. However, men with metastatic castrate-resistant prostate
      cancer have incurable disease with poor survival despite intensive therapy. This
      unmet need has led to recent advances in therapy aimed at treating bone
      metastases resulting from prostate cancer. The bone microenvironment lends itself
      to metastases in castrate-resistant prostate cancer, as a result of complex
      interactions between the microenvironment and tumor cells. The development of
      223radium dichloride (Ra-223) to treat symptomatic bone metastases has improved
      survival in men with metastatic castrate-resistant prostate cancer. Moreover, Ra
      223 may have effects on the tumor microenvironment that enhance its activity. Ra
      223 treatment has been shown to prolong survival, and its effects on the immune
      system are under investigation. Because prostate cancer affects a sizable portion
      of the adult male population, understanding how it metastasizes to bone is an
      important step in advancing therapy. Clinical trials that are underway should
      yield new information on whether Ra-223 synergizes effectively with immunotherapy
      agents and whether Ra-223 has enhancing effects on the immune system in patients
      with prostate cancer.

PMID- 29380086
TI  - A case for methodological overhaul and increased study of executive function in
      the domestic dog (Canis lupus familiaris).
AB  - Executive function (EF) allows for self-regulation of behavior including
      maintaining focus in the face of distraction, inhibiting behavior that is
      suboptimal or inappropriate in a given context, and updating the contents of
      working memory. While EF has been studied extensively in humans, it has only
      recently become a topic of research in the domestic dog. In this paper, I argue
      for increased study of dog EF by explaining how it might influence the owner-dog
      bond, human safety, and dog welfare, as well as reviewing the current literature
      dedicated to EF in dogs. In "EF and its Application to "Man's Best Friend"
      section, I briefly describe EF and how it is relevant to dog behavior. In
      "Previous investigations into EF in dogs" section, I provide a review of the
      literature pertaining to EF in dogs, specifically tasks used to assess abilities
      like inhibitory control, cognitive flexibility, and working memory capacity. In
      "Insights and limitations of previous studies" section, I consider limitations of
      existing studies that must be addressed in future research. Finally, in "Future
      directions" section, I propose future directions for meaningful research on EF in
      dogs.

PMID- 29380087
TI  - Issues in data expansion in understanding criticality in biological systems.
AB  - At the point of a second-order phase transition also termed as a critical point,
      systems display long-range order and their macroscopic behaviors are independent
      of the microscopic details making up the system. Due to these properties, it has
      long been speculated that biological systems that show similar behavior despite
      having very different microscopics, may be operating near a critical point.
      Recent methods in neuroscience are making it possible to explore whether
      criticality exists in neural networks. Despite being large in size, many datasets
      are only a minute sample of the neural system and methods have to be developed to
      expand these datasets to study criticality. In this work we develop an analytical
      method of expanding a dataset to the large N limit to make statements about the
      critical nature of the dataset. We show that different ways of expanding the
      dataset while keeping its variance and mean fixed yield different results
      regarding criticality. This hence casts doubts on the established procedures for
      deducing criticality of biological systems through expansion of finite-sized
      datasets.

PMID- 29380088
TI  - It is time to move forward into the era of Theranostics.
AB  - Radionuclide therapy, which until 15 years ago included only a few approved
      therapies, is gaining importance in the treatment of various malignancies. The
      future of oncology will not be limited to surgery, chemo-, antibody therapies or
      external radiation; it will include targeted therapy with radionuclides, which
      will become the standard of care for a variety of malignant diseases in
      combination or as an alternative to other therapies. Therefore there is a need to
      train Nuclear Oncologists, who are able to approach oncological diseases, promote
      development of radiopharmacy, understand the biology of radionuclide treatment,
      apply radionuclide treatments and be able to use molecular imaging such as PET/CT
      and SPECT/CT for treatment planning and dosimetry.

PMID- 29380089
TI  - Young Adult Retrospective Reports of Adverse Childhood Experiences: Prevalence of
      Physical, Emotional, and Sexual Abuse in Italy.
AB  - This study sought to understand the prevalence of childhood abuse in Italy using
      an instrument developed by the International Society for the Prevention of Child
      Abuse and Neglect (ISPCAN) and adapted to the Italian context. The study
      participants were 312 young adults, 106 males (34%), and 206 females (64%), aged
      18-24 years, from various northwest Italian universities and workplaces, using an
      ISPCAN Child Abuse Screening Tool retrospective questionnaire (ICAST-R). With
      reference to comparative data from other countries, the Italian context reveals a
      high incidence of emotional abuse (62%) followed by physical abuse (44%) and
      sexual abuse (18%). While males reported more physical abuse, females reported
      more exposure to sexual and emotional abuse. Moreover, the validity of the ICAST
      instrument was evaluated. The internal consistency for the three subscales was
      similar to the findings of previous studies, with Cronbach's alphas ranging from
      0.51 for emotional abuse to 0.59 for sexual abuse. We observe that children
      undergo forms of emotional and physical maltreatment for disciplinary purposes,
      and for this reason, such abuse is excused. Greater prevention measures should be
      adopted in this direction. Finally, our study has contributed to the validation
      of the ICAST-R instrument for use in the Italian context.

PMID- 29380090
TI  - The Relationship Between Psychological Temporal Perspective and HIV/STI Risk
      Behaviors Among Male Sex Workers in Mexico City.
AB  - Men who have sex with men (MSM) face a disproportionate burden of HIV incidence
      and HIV prevalence, particularly young men who have sex with men. The aim of this
      article was to analyze the relation between a psychological temporal perspective
      and HIV/sexually transmitted infection (STI) risk behaviors among male sex
      workers (MSWs), a potentially highly present-oriented group of MSM. A total
      sample of 326 MSWs were included and responded to a validated psychological
      scale: the Zimbardo's Time Perspective Inventory; they also reported how
      frequently they engaged in protective behaviors against HIV and other STI risks
      behaviors, including condom use with casual and regular partners, as well as
      prior HIV testing. We adjusted structural equation models to analyze the relation
      between a psychological temporal perspective and HIV/STI risk behaviors. We found
      that orientation toward the past was correlated with decreased condom use with
      casual partners (beta = - 0.18; CI95% - 0.23, - 0.12). Future orientation was not
      associated with condom use with casual partners. Regarding condom use with
      regular partners, past and present orientation were related to lower likelihood
      of condom use (beta = - 0.23; CI95% - 0.29, - 0.17; beta = - 0.11; CI95% - 0.19, 
      0.02), whereas future orientation increased the likelihood of condom use with
      regular partners (beta = 0.40; CI95% 0.31, 0.50). Time orientation (past,
      present, or future) did not predict the probability of having an HIV test. The
      design of HIV/STI prevention programs among vulnerable populations, such as MSM
      and MSWs, should consider specific time-frame mechanisms that can importantly
      affect sexual risk behavior decisions.

PMID- 29380091
TI  - The gastric carcinosarcoma with severe venous invasion: a case report.
AB  - BACKGROUND: Gastric carcinosarcoma with severe venous invasion is extremely rare,
      and to the best of our knowledge, this is the first reported case. CASE
      PRESENTATION: A 79-year-old man visited the Onomichi General Hospital following
      abnormal upper gastrointestinal series findings. Laboratory data demonstrated no
      anemia, and the serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19
      9 (CA19-9) levels were not elevated. Endoscopy identified a Borrmann type III
      lesion in the cardiac end of the stomach. Abdominal contrast-enhanced
      computerized tomography (CT) indicated that the lesser curvature of the stomach
      wall was modestly enhanced with bulky lymph nodes. Pathological biopsy
      examination identified a group 5, papillary adenocarcinoma. We diagnosed advanced
      gastric cancer with bulky lymph nodes (cT4aN3M0, cStage IIIC). Following
      neoadjuvant chemotherapy, the patient underwent open total gastrectomy with D2
      lymph node dissection. Histopathologically, the tumor consisted of two
      components: a tubular adenocarcinoma and a sarcoma. The tumor cells were mainly
      intravenous and were not detected in the gastric wall stroma; this resulted in a
      venous invasion. Immunohistochemical analysis revealed that the tumor was
      positive for vimentin and partly positive for desmin and cytokeratin CAM5.2. We
      diagnosed a true gastric carcinosarcoma with severe venous invasion. Abdominal CT
      2 months after surgery showed a low density area in the liver, suggesting
      metastasis. CONCLUSIONS: Carcinosarcomas with lymph node metastasis are sometimes
      reported, but progression into the vasculature is very rare. We present a case of
      carcinosarcoma with unusual progression characteristics.

PMID- 29380092
TI  - Clinical Significance of Skeletal Muscle Loss Following Lung Resection for
      Cancer: Recovery and Sarcopenia are Linked to Cancer Outcomes.

PMID- 29380093
TI  - Survival Prediction in Pancreatic Ductal Adenocarcinoma by Quantitative Computed
      Tomography Image Analysis.
AB  - BACKGROUND: Pancreatic cancer is a highly lethal cancer with no established a
      priori markers of survival. Existing nomograms rely mainly on post-resection data
      and are of limited utility in directing surgical management. This study
      investigated the use of quantitative computed tomography (CT) features to
      preoperatively assess survival for pancreatic ductal adenocarcinoma (PDAC)
      patients. METHODS: A prospectively maintained database identified consecutive
      chemotherapy-naive patients with CT angiography and resected PDAC between 2009
      and 2012. Variation in CT enhancement patterns was extracted from the tumor
      region using texture analysis, a quantitative image analysis tool previously
      described in the literature. Two continuous survival models were constructed,
      with 70% of the data (training set) using Cox regression, first based only on
      preoperative serum cancer antigen (CA) 19-9 levels and image features (model A),
      and then on CA19-9, image features, and the Brennan score (composite pathology
      score; model B). The remaining 30% of the data (test set) were reserved for
      independent validation. RESULTS: A total of 161 patients were included in the
      analysis. Training and test sets contained 113 and 48 patients, respectively.
      Quantitative image features combined with CA19-9 achieved a c-index of 0.69
      [integrated Brier score (IBS) 0.224] on the test data, while combining CA19-9,
      imaging, and the Brennan score achieved a c-index of 0.74 (IBS 0.200) on the test
      data. CONCLUSION: We present two continuous survival prediction models for
      resected PDAC patients. Quantitative analysis of CT texture features is
      associated with overall survival. Further work includes applying the model to an
      external dataset to increase the sample size for training and to determine its
      applicability.

PMID- 29380094
TI  - "Psychological Boarding" and Community-Based Behavioral Health Crisis
      Stabilization.
AB  - This exploratory paper presents a case study where a community based mental
      health organization forging a partnership with a local hospital system to
      establish a crisis stabilization unit (CSU) to address behavioral health
      emergency care. The study takes a mixed methods case study approach to address
      two research questions; (a) did this approach reduce the overall length of stay
      in the hospital emergency departments? (b) What challenges did the taskforce face
      in implementing this CSU model? The paper shares recommendation from the
      findings.

PMID- 29380095
TI  - Study of tensiometric properties, microbiological and collagen content in nile
      tilapia skin submitted to different sterilization methods.
AB  - Tissue bioengineering development is a global concern and different materials are
      studied and created to be safe, effective and with low cost. Nile Tilapia skin
      had shown its biological potential as covers for the burn wound. This study
      evaluates the tilapia skin histological, collagen properties and tensiometric
      resistance, after treatment by different sterilization methods. Tilapia skin
      samples were submitted to two sterilization processes: (1) chemical, which
      consisted in two 2% chlorhexidin baths, followed by sequential baths in
      increasing glycerol concentrations; and (2) radiation, when glycerolized skin
      samples were submitted to gamma radiation at 25, 30 and 50 kGy. Microscopic
      analyzes were performed through Haematoxylin-eosin and Picrosirius Red under
      polarized light. For tensiometric analysis, traction tests were performed.
      Glycerol treated skin presented a discrete collagen fibers disorganization within
      the deep dermis, while irradiated skin did not show any additional change.
      Throughout the steps of chemical sterilization, there was a higher proportion of
      collagen with red/yellow birefringence (type I) in the skin samples up to the
      first bath in chlorhexidin, when compared to samples after the first two glycerol
      baths (P < 0.005). However, there was no difference in relation to total collagen
      between groups. In irradiated skin, there was a larger total collagen
      preservation when using until 30 kGy (P < 0.005). Tensiometric evaluation did not
      show significant differences in relation to maximum load in the groups studied.
      We concluded that chemical and radiation (25 and 30 kGy) are efficient methods to
      sterilize Nile Tilapia skin without altering its microscopic or tensiometric
      characteristics.

PMID- 29380096
TI  - The Impact of Acculturation and Racialization on Self-Rated Health Status Among
      U.S. Latinos.
AB  - We investigate the Hispanic paradox by examining the relationship between
      acculturation and health status of Latinos to understand nuances among this
      growing heterogeneous population using a 2011 Latino Decisions survey. We find
      that acculturation remains an important determinant of Latino health; however,
      this varies based on whether the sample is restricted to immigrants or includes
      all Latino adults and on the measures of acculturation employed. We find Latino
      citizens reported better health than non-citizens; however, other acculturation
      measures, such as language use and time in the U.S. do not have a marked effect.
      Furthermore, skin color matters only for U.S.-born Latinos. Racialization is
      therefore important to consider within the context of the Hispanic paradox. Our
      findings suggest that some of the disadvantages stemming from minority status in
      the U.S. are more prominent among Latinos who have greater experience with the
      racial hierarchy of the U.S. and greater acculturation more broadly.

PMID- 29380097
TI  - Depression score changes in response to sleep disordered breathing treatment with
      positive airway pressure in a large clinic-based cohort.
AB  - OBJECTIVE: The clinical-population impact of positive airway pressure (PAP) on
      depressive symptoms in sleep disordered breathing (SDB) awaits clear
      documentation. We hypothesized that depressive symptoms improve in response to
      PAP treatment in a large clinical setting, and that lower socio-economic status
      poses barriers to full therapeutic response. METHOD: We performed a retrospective
      cohort study of SDB patients attending a tertiary ambulatory sleep center between
      January 1, 2010 and December 31, 2015. Data extracted from electronic health
      records included Patient Health Questionnaire-9 (PHQ-9) scores, demographic
      characteristics, PAP adherence, and medical history. Paired- and two-sample t
      tests were utilized to assess changes in PHQ-9 score according to PAP adherence.
      Linear regression models were constructed to evaluate the association of
      socioeconomic status (SES) and other clinical variables on PHQ-9 scores. RESULTS:
      The cohort consisted of 1981 SDB patients (56.4 +/- 13.3 years; 45.7% female;
      76.2% Caucasian). Regardless of adherence, PAP therapy improved PHQ-9 scores (-
      2.4 +/- 4.6, p < 0.0001), with more robust responses in patients with baseline
      PHQ-9 scores > 10 (- 4.8 +/- 5.7; p < 0.0001). Adherent patients had
      significantly greater improvement (- 2.8 +/- 4.4 vs. 1.6 + 4.2, p < 0.0001), and
      even greater benefit if baseline PHQ-9 was > 10 (-6.0 +/- 5.3 vs. - 3.8 +/- 4.9,
      p < 0.001). Patients from lower socioeconomic status and greater depressive
      symptom had worse post-PAP PHQ-9 scores. CONCLUSIONS: PAP therapy and adherence
      were associated with improvement in depressive symptom severity in this clinical
      cohort. Patients with lower socioeconomic status derived less therapeutic
      benefit, suggesting that they faced additional barriers to treatment
      effectiveness.

PMID- 29380098
TI  - Impact of sleep-related breathing disorder on motor and non-motor symptoms in
      multiple system atrophy.
AB  - INTRODUCTION: Although several studies suggested that sleep-related breathing
      disorder (SRBD) is a frequent symptom of multiple system atrophy (MSA), whether
      SRBD has influence on the motor and non-motor symptoms of MSA is unknown.
      METHODS: A total of 40 MSA patients and 40 healthy volunteers (HVs) underwent
      video-polysomnography (PSG) in the current study. All the MSA individuals were
      assessed using the Epworth Sleepiness Scale (ESS), Unified Multiple-System
      Atrophy Rating Scale (UMSARS), Hamilton Depression Scale (HAMD), Hamilton Anxiety
      Scale, Frontal assessment battery (FAB), Parkinson's Disease Questionnaire-39
      (PDQ-39), and the Montreal Cognitive Assessment (MoCA). RESULTS: We found apnea
      hypopnea index (AHI) of the MSA patients recorded by PSG was 16.4 +/- 20.2. SRBD
      was found in 65% of the MSA patients (26/40), which was significantly higher than
      HVs (8/40, 20%) (p = 0.0001). Compared to the MSA patients without SRBD, MSA
      individuals with SRBD showed higher total UMSARS, UMSARS-II, FAB, and HAMD
      scores, more frequent occurrence of excessive daytime sleepiness, hypopneas,
      longer mean times for hypopneas, and obstructive sleep apnea (OSA), as well as
      longer time for OSA. This study suggested that SRBD is frequently seen in MSA
      patients. CONCLUSION: MSA individuals with SRBD are prone to be severe motor
      deficits, depression, frontal lobe dysfunction, and excessive daytime sleepiness.

PMID- 29380099
TI  - Commentary: PREMM5 threshold of 2.5% is recommended to improve identification of
      PMS2 carriers.

PMID- 29380100
TI  - Heterologous co-expression in E. coli of isoamylase genes from cassava Manihot
      esculenta Crantz 'KU50' achieves enzyme-active heteromeric complex formation.
AB  - KEY MESSAGE: Cloning of two isoamylase genes, MeISA1 and MeISA2, from cassava
      (Manihot esculenta Crantz) tubers, accompanied by their co-expression in E. coli
      demonstrates a requirement for heteromeric complex formation to achieve
      debranching activity. Starch debranching enzyme (DBE) or isoamylase (ISA)
      (EC.3.2.1.68), an important enzyme in starch metabolism, catalyses the hydrolysis
      of alpha-1,6 glycosidic linkages of amylopectin. Isoforms of ISAs have been
      reported in higher plants and algae (Fujita et al. in Planta 208:283-293, 1999;
      Hussain et al. in Plant Cell 15:133-149, 2003; Ishizaki et al. in Agric Biol Chem
      47:771-779, 1983; Mouille et al. in Plant Cell 8:1353-1366, 1996). In the current
      work, cassava ISA genes were isolated from cDNA generated from total RNA from
      tubers of Manihot esculanta Crantz cultivar KU50. MeISA1 and MeISA2 were
      successfully amplified and cloned into a pETDuet1 vector. The putative MeISA1 and
      MeISA2 proteins comprised 763 and 882 amino acids, with substantial similarity to
      StISA1 and StISA2 from potato (84.4% and 68.9%, respectively). Recombinant MeISA1
      and MeISA2 were co-expressed in Escherichia coli SoluBL21 (DE3). HistrapTM
      Purified rMeISA1 and rMeISA2 showed approximate molecular weights of 87 and 99
      kDa, respectively, by SDS-PAGE. Debranching activity was only detectable in the
      column fractions where both recombinant ISA isoforms were present. The
      heteromeric DBE from crude extracts of 4-5 h induced cultures analysed by gel
      filtration chromatography and western blot showed combinations of rMeISA1 and
      rMeISA2 at ratios of 1:1 to 4:1. Pooled fractions with DBE activity were used for
      enzyme characterisation, which showed that the enzyme was specific for
      amylopectin, with optimum activity at 37  degrees C and pH 7.0. Enzyme activity
      was enhanced by Co2+, Mg2+ and Ca2+, but was strongly inhibited by Cu2+.
      Debranched amylopectin products showed chain length distributions typical of
      plant DBE.

PMID- 29380101
TI  - MR arthrographic demonstration of an unusual multiplication anomaly concerning
      the glenohumeral ligaments.
AB  - The glenohumeral ligaments (GHLs), localized thickenings of the anterior joint
      capsule, are important passive stabilizers of the shoulder joint. A 29-year-old
      man was admitted for evaluation of left shoulder pain. The conventional magnetic
      resonance (MR) imaging showed a thickened anterior labroligamentous complex. MR
      arthrography revealed a multiplication anomaly of all the GHLs. The purpose of
      this study was to demonstrate the MR arthrography findings of this unusual
      anatomic variation of the GHLs.

PMID- 29380102
TI  - Circumportal pancreas: prevalence, subtypes and vascular variations of 55
      patients.
AB  - PURPOSE: To determine the frequency of circumportal pancreas (CP), and
      accompanying ductal and vascular anatomy variations. METHODS: Thin-section
      multidetector computed tomography of 6813 consecutive patients was
      retrospectively reviewed. Two radiologists evaluated CP presence with consensus.
      Concomitant pancreatic ductal and vascular variations were recorded. The course
      of the pancreatic duct was classified according to the portal vein as anteportal
      and retroportal, and pancreas fusion level classified according to splenic vein
      as suprasplenic, infrasplenic and mixed type. RESULTS: A total of 55 (0.8%) CP
      cases were detected. Six suprasplenic subtype cases were excluded from the
      classification, because the pancreatic ducts were not clearly distinguishable.
      Suprasplenic anteportal (45/49, 92%), infrasplenic anteportal (2/49, 4%),
      suprasplenic retroportal (1/49, 2%), and mixed anteportal subtypes (1/49, 2%)
      were detected. There were vascular variations in 16 cases (29%). 13/16 (81%) of
      vascular variations were detected on suprasplenic anteportal subtype. Most of
      them were replaced right hepatic artery from the superior mesenteric artery (n:
      6). CONCLUSIONS: CP is a rare but important pancreatic fusion anomaly.
      Suprasplenic anteportal CP is the most common subtype and other subtypes are very
      rare. Replaced right hepatic artery from the superior mesenteric artery is the
      most frequent vascular variation associated with CP. Identifying the CP and
      defining the pancreatic duct and vascular variations are important to prevent
      possible complications in patients undergoing pancreatic surgery.

PMID- 29380103
TI  - Anatomical and histological study of the deep neck fasciae: does the alar fascia
      exist?
AB  - PURPOSE: The aim of this study was to determine whether the alar fascia is a
      distinct layer of the deep cervical neck fasciae. The present study also aimed to
      elucidate the anatomical limits of this fascia. METHODS: Neck dissections of ten
      adult cadavers were performed, layer by layer, in the retropharyngeal region,
      under a powered operating microscope. Detailed dissections revealed the
      anatomical limits of the deep neck fasciae. Histological descriptions were also
      performed on large tissue samples collected from three cervical dissections.
      RESULTS: In the ten dissections, three layers of fascia were identified and
      dissected in the retropharyngeal region: a visceral fascia, a prevertebral fascia
      and an alar fascia. The alar fascia appeared like a connecting band derivative of
      the visceral fascia, between both vascular sheaths. It fused completely with the
      visceral fascia anteriorly at the level of T2 and with the prevertebral fascia
      posteriorly at the level of C1. No sagittal connection between the visceral
      fascia and the prevertebral fascia was identified. The stained histological
      sections confirmed the presence of the visceral and prevertebral fasciae at the
      oropharyngeal level, with a third intermediate layer closely connected with the
      visceral fascia. CONCLUSION: The alar fascia is a layer of the cervical neck
      fascia connected with the visceral fascia from C1 to T2 levels. The anatomical
      limits of this alar fascia and its relationships with the internal carotid artery
      are important in the surgical management and the prognosis of deep neck
      infections and retropharyngeal lymph node metastases.

PMID- 29380104
TI  - Assessment of tautomer distribution using the condensed reaction graph approach.
AB  - We report the first direct QSPR modeling of equilibrium constants of tautomeric
      transformations (logK T ) in different solvents and at different temperatures,
      which do not require intermediate assessment of acidity (basicity) constants for
      all tautomeric forms. The key step of the modeling consisted in the merging of
      two tautomers in one sole molecular graph ("condensed reaction graph") which
      enables to compute molecular descriptors characterizing entire equilibrium. The
      support vector regression method was used to build the models. The training set
      consisted of 785 transformations belonging to 11 types of tautomeric reactions
      with equilibrium constants measured in different solvents and at different
      temperatures. The models obtained perform well both in cross-validation (Q2 =
      0.81 RMSE = 0.7 logK T units) and on two external test sets. Benchmarking studies
      demonstrate that our models outperform results obtained with DFT B3LYP/6-311 ++
      G(d,p) and ChemAxon Tautomerizer applicable only in water at room temperature.

PMID- 29380105
TI  - Coffee or Tea? A prospective cohort study on the associations of coffee and tea
      intake with overall and cause-specific mortality in men versus women.
AB  - Coffee and tea intake have been associated with reduced mortality, but no studies
      have investigated possible substitution effects. The relationship of mortality
      with coffee, tea, and substituting coffee with tea was investigated in the
      Netherlands Cohort Study. In 1986, 120,852 men and women aged 55-69 years
      provided information on dietary and lifestyle habits. Mortality follow-up until
      1996 consisted of linkage to Statistics Netherlands. Multivariate case-cohort
      analyses were based on 8665 deaths and 3166 subcohort members with complete data
      on coffee, tea and confounders. Higher coffee intake was significantly,
      nonlinearly related to lower overall and cause-specific mortality in women. In
      men, coffee was significantly positively related to cancer and cardiovascular
      mortality, and inversely to respiratory and other causes of death. Tea intake was
      significantly, nonlinearly related to lower overall, cancer and cardiovascular
      mortality in men, but showed no association with mortality in women. In
      substitution analyses, increasing the proportion tea (replacing coffee with tea)
      was significantly and nonlinearly related to lower overall, cancer and
      cardiovascular mortality in men, but in women higher tea proportions were
      positively associated with overall mortality (and most causes of death). This
      study suggests that for men, compared to exclusive coffee drinkers, those
      drinking 30-50% tea showed the lowest mortality; any tea drinking seemed better
      than only coffee. For women, those who drank exclusively coffee or drinking up to
      40% tea had the lowest mortality, but those drinking higher percentages of tea
      were at increased mortality risk [HR = 1.41 (95% CI 1.01-1.99) for 80-100% tea
      compared to exclusive coffee drinkers].

PMID- 29380106
TI  - Simultaneous detection of circulating and disseminated tumor cells in primary
      breast cancer patients following neoadjuvant chemotherapy.
AB  - PURPOSE: Pathological complete response (pCR) is a common endpoint in neoadjuvant
      chemotherapy (NACT) of primary breast cancer patients (PBC), but does not address
      the systemic prevalence of minimal residual disease. In this study, we compared
      pCR with the detection of circulating (CTC) and disseminated tumor cells (DTC)
      following NACT, as well as their impact on survival. METHODS: Patients with PBC
      receiving NACT and consecutive surgery were eligible for this study. CTCs were
      detected using the CellSearch(r) system and DTCs were determined using
      immunocytochemistry (cytokeratin staining with the A45-B/B3 antibody). pCR was
      defined as ypT0/ypTis and ypN0. RESULTS: 58 patients were included in the
      analysis with a median follow-up of 30 months. Of these, 5 (9%) presented with
      CTCs and 36 (62%) with DTCs. 16 patients (28%) achieved a pCR. No significant
      correlation between CTCs, DTCs and pCR and no statistically significant impact on
      disease free (DFS) or overall survival (OS) was apparent. CONCLUSIONS: Both CTCs
      and DTCs are detectable after NACT. As we could not show a significant
      relationship between CTC detection, DTC detection and pCR, all three methods may
      provide independent information regarding treatment response. Since we were
      unable to show a significant impact on survival, larger prospective studies that
      include CTCs and DTCs are needed. These trials should include the molecular
      characterization of primary tumor tissue, CTCs and DTCs to determine whether
      these cells are independent subpopulations of malignant cell clones.

PMID- 29380107
TI  - Prognostic role of mesenteric lymph nodes involvement in patients undergoing
      posterior pelvic exenteration during radical or supra-radical surgery for
      advanced ovarian cancer.
AB  - PURPOSE: The aim of this retrospective study is to analyze the prognostic role
      and the practical implication of mesenteric lymph nodes (MLN) involvements in
      advanced ovarian cancer (AOC). METHODS: A total of 429 patients with AOC
      underwent surgery between December 2007 and May 2017. We included in the study 83
      patients who had primary (PDS) or interval debulking surgery (IDS) for AOC with
      bowel resection. Numbers, characteristics and surgical implication of MLN
      involvement were considered. RESULTS: Eighty-three patients were submitted to
      bowel resection during cytoreduction for AOC. Sixty-seven patients (80.7%)
      underwent primary debulking surgery (PDS). Sixteen patients (19.3%) experienced
      interval debulking surgery (IDS). 43 cases (51.8%) showed MLN involvement. A
      statistic correlation between positive MLN and pelvic lymph nodes (PLN) (p =
      0.084), aortic lymph nodes (ALN) (p = 0.008) and bowel infiltration deeper than
      serosa (p = 0.043) was found. A longer overall survival (OS) and disease-free
      survival was observed in case of negative MLN in the first 20 months of follow
      up. No statistical differences between positive and negative MLN in terms of
      operative complication, morbidity, Ca-125, type of surgery (radical vs supra
      radical), length and site of bowel resection, residual disease and site of
      recurrence were observed. CONCLUSIONS: An important correlation between positive
      MLN, ALN and PLN was detected; these results suggest a lymphatic spread of
      epithelial AOC similar to that of primary bowel cancer. The absence of residual
      disease after surgery is an independent prognostic factor; to achieve this result
      should be recommended a radical bowel resection during debulking surgery for AOC
      with bowel involvement.

PMID- 29380108
TI  - Do coverage mandates affect direct-to-consumer advertising for pharmaceuticals?
      Evidence from parity laws.
AB  - Direct-to-consumer advertising (DTCA) for prescription drugs is a relatively
      unique feature of the US health care system and a source of tens of billions of
      dollars in annual spending. It has also garnered the attention of researchers and
      policymakers interested in its implications for firm and consumer behavior.
      However, few economic studies have explored the DTCA response to public policies,
      especially those mandating coverage of these products. We use detailed
      advertising expenditure data to assess if pharmaceutical firms increase their
      marketing efforts after the implementation of relevant state and federal health
      insurance laws. We focus on mental health parity statutes and related drug
      therapies-a potentially ripe setting for inducing stronger consumer demand. We
      find no clear indication that firms expect greater value from DTCA after these
      regulatory changes. DTCA appears driven by other considerations (e.g., product
      debut); however, it remains a possibility that firms respond to these laws
      through other, unobserved channels (e.g., provider detailing).

PMID- 29380109
TI  - Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin
      3 expression in the colon.
AB  - Daiokanzoto (DKT) exerts its laxative effect via colonic inflammation caused by
      sennoside A in Daio (rhubarb). Previously, we showed that the laxative effect of
      sennoside A is related to decreased aquaporin-3 (AQP3) expression in mucosal
      epithelial cells due to colonic inflammation. We also found that a combination of
      glycyrrhizin, an ingredient in Kanzo (glycyrrhiza), and sennoside A attenuates
      the inflammatory response induced by sennoside A and reduces its laxative effect.
      These findings indicate that DKT may be a long-term treatment for chronic
      constipation, but there is no evidence supporting this hypothesis. In this study,
      we analyzed the laxative effect of repeated DKT administration, focusing on AQP3
      expression in the colon. After rats were treated for 7 days, decreased AQP3
      expression and the onset of diarrhea were observed in the DKT group, but were not
      seen in the Daio group either. Although the relative abundance of gut microbiota
      after repeated DKT administration was similar to that after control treatment,
      Daio reduced Lactobacillaceae, Bifidobacteriaceae, and Bacteroidaceae levels and
      markedly increased Lachnospiraceae levels. In this study, we show that DKT has a
      sustained laxative effect, even upon repeated use, probably because it maintains
      decreased AQP3 expression and gut microbiota homeostasis. This outcome therefore
      indicates that DKT can be used as a long-term treatment for chronic constipation.

PMID- 29380110
TI  - Fall in thyroid stimulating hormone (TSH) may be an early marker of ipilimumab
      induced hypophysitis.
AB  - PURPOSE: Hypophysitis develops in up to 19% of melanoma patients treated with
      ipilimumab, a cytotoxic T-lymphocyte antigen-4 antibody. Early detection may
      avert life-threatening hypopituitarism. We aimed to assess the incidence of
      ipilimumab-induced hypophysitis (IH) at a quaternary melanoma referral centre,
      and to determine whether cortisol or thyroid stimulating hormone (TSH) monitoring
      could predict IH onset. METHODS: We performed a retrospective cohort study of
      ipilimumab-treated patients at a quaternary melanoma referral centre in
      Australia. The inclusion criteria were patients with metastatic or unresectable
      melanoma treated with ipilimumab monotherapy, and cortisol and TSH measurements
      prior to >= 2 infusions. The main outcomes were IH incidence and TSH and cortisol
      patterns in patients who did and did not develop IH. RESULTS: Of 78 ipilimumab
      treated patients, 46 met the study criteria and 9/46 (20%) developed IH at a
      median duration of 13.0 weeks (range 7.7-18.1) following ipilimumab initiation.
      All patients whose TSH fell >= 80% compared to baseline developed IH, and, in 5/9
      patients with IH, TSH fell prior to cortisol fall and IH diagnosis. Pre-cycle-4
      TSH was significantly lower in those who developed IH (0.31 vs. 1.73 mIU/L, P =
      0.006). TSH fall was detected at a median time of 9.2 (range 7.7-16.4) weeks
      after commencing ipilimumab, and a median of 3.6 (range of - 1.4 to 9.7) weeks
      before IH diagnosis. There was no difference in TSH between the groups before
      cycles 1-3 or in cortisol before cycles 1-4. CONCLUSIONS: TSH fall >= 80% may be
      an early marker of IH. Serial TSH measurement during ipilimumab therapy may be an
      inexpensive tool to expedite IH diagnosis.

PMID- 29380111
TI  - A porencephalic cyst formation in a 6-year-old female with a functioning
      ventriculoperitoneal shunt: a case-based review.
AB  - INTRODUCTION: Porencephalic cysts and cerebrospinal fluid (CSF) edema around the
      intracranial shuntcatheter are rare complications of ventriculoperitoneal shunt
      (VPS) surgery. Possible mechanisms leading to a porencephalic cyst formation in a
      patient with a VPS include taut ventricle, dysfunction of distalcatheters, and
      irreversible damage to the brain parenchyma caused by shunt insertion,
      chemotherapy, or radiation. Most of the previous reports were due to shunt
      malfunction and treatment consisted of shunt revision or removal. CASE REPORT: We
      present a case of porencephalic cyst formation in a 6-year-old female as a result
      ofcerebrospinal fluid under-drainage that was promptly improved with shunt valve
      adjustment. COCLUSIONS: A heightened index of suspicion is required to prevent
      misdiagnosis of porencephalic cysts astumors or abscesses that may lead to
      unnecessary surgical explorations. Further research is needed toelucidate the
      pathophysiological mechanism that causes a porencephalic cyst formation.

PMID- 29380112
TI  - Use of neuroimaging measurements of optic nerve sheath diameter to assess
      intracranial pressure in craniosynostosis.
AB  - PURPOSE: This study aims to evaluate accuracy of optic nerve sheath diameter
      (ONSD) measurements obtained by magnetic resonance imaging (MRI) in patients with
      craniosynostosis (CS) for detection of high intracranial pressure (ICP) and to
      correlate MRI-derived ONSD measurements with those obtained by computed
      tomography (CT) scans in CS patients. METHODS: A retrospective review was
      conducted on CS patients who had MRI- and age-matched controls with normal MRI.
      Diagnosis of intracranial hypertension was based on presence of papilledema,
      direct ICP monitoring, and/or lumbar puncture. The search also included patients
      with MRI and CT done within 30 days apart. ONSDs were measured 3 mm behind the
      globe on both modalities. RESULTS: The study identified 56 CS patients (mean age
      3.8 +/- 3.47 years) and 49 controls (mean age 3.7 +/- 3.62 years). Mean ONSD in
      patients with high ICP was significantly higher than in patients without high ICP
      (P = 0.0001) and in controls (P < 0.0001). The optimal ONSD threshold for
      predicting raised ICP in patients >1 year old was 6 mm (71.4% sensitivity, 89.7%
      specificity). Nineteen patients with 38 single-eye MRI/CT pairs were identified.
      Substantial agreement between both modalities resulted (r = 0.959, 95% CI 0.923
      0.978), and Bland and Altman Plot analysis showed that 95% of measurements fell
      within limits of agreement (1.96 SD; +/- 0.6 mm). CONCLUSION: In CS patients,
      ONSD measured by MRI represent indirect non-invasive means of ICP assessment.
      Both MRI and CT measurements of ONSD gave comparable results, and the use of CT
      derived ONSD measurements may give some idea about ICP in CS patients.

PMID- 29380113
TI  - Complex congenital atlantoaxial dislocation in an infant: case report.
AB  - The authors report the case of congenital atlantoaxial dislocation in a 9-month
      old female infant, who presented with progressive quadriparesis and respiratory
      failure. The problems in management due to such an early age of presentation,
      including atypical clinical presentation, unique radiological findings, limited
      management options, and variable clinical outcomes discussed. This is the
      youngest case of non-syndromic congenital atlantoaxial dislocation, reported to
      date, and is a unique combination of lateral, rotatory, and antero-posterior
      atlantoaxial dislocation.

PMID- 29380114
TI  - Unique combination of myxopapillary ependymoma and conus lipoma with subcutaneous
      extension in an 11-month-old child.

PMID- 29380115
TI  - Effects of Diet-Induced Obesity on Tracheal Responsiveness to Methacholine,
      Tracheal Visfatin Level, and Lung Histological Changes in Ovalbumin-Sensitized
      Female Wistar Rats.
AB  - Many studies have shown a close relationship between obesity and asthma severity.
      In the present study, the effects of diet-induced obesity were examined on airway
      responsiveness to methacholine in addition to visfatin level in female Wistar
      rats' tracheae after sensitization with ovalbumin. The rats were divided into
      four groups: control with normal diet (ND), ovalbumin (OVA)-sensitized with
      normal diet (S + ND), high-fat diet (HFD), and OVA-sensitized with a high-fat
      diet (S + HFD). The animals were fed for 8 weeks with standard pelts or high-fat
      diet and then sensitized and challenged with OVA or saline for another 4 weeks.
      At the end of the study, the tracheae were isolated and assessed for airway
      responsiveness and visfatin protein levels. Diet-induced obesity groups developed
      increased weight and obesity indices (p < 0.001). After sensitization with OVA
      and diet-induced obesity, there were marked leftward shifts in methacholine
      concentration-response curves in S + HFD group compared to other groups. Also,
      maximum response was the highest (p < 0.05 to p < 0.001), EC50 was the lowest (p
      < 0.05 to p < 0.001), and visfatin protein level was the highest (p < 0.05 to p <
      0.01) in S + HFD. According to results, diet-induced obesity caused airway
      hyperresponsiveness to methacholine and enhanced visfatin protein levels in the
      tracheae of ovalbumin-sensitized female rats. Our results suggested that, in
      obese ovalbumin-sensitized conditions in female rats, the local production of
      adipocytokines, such as visfatin, may be increased, resulting in the
      deterioration of inflammation in lungs. This finding shows a possible mechanism
      for the altered phenotype in obesity-ovalbumin sensitization conditions in female
      rats.

PMID- 29380117
TI  - Acinar Cell Cystadenoma of the Pancreas: a Multidisciplinary and Contemporary
      Approach.

PMID- 29380116
TI  - Diabetes and Abdominal Aortic Calcification-a Systematic Review.
AB  - PURPOSE OF REVIEW: A systematic literature review was performed to evaluate
      diabetes mellitus (DM) as a risk factor of abdominal aortic calcification (AAC),
      and address factors that might contribute to the development of AAC in DM
      patients. RECENT FINDINGS: DM is an independent risk factor of AAC development.
      Bone metabolism along with lifestyle factors among DM patients makes them more
      prone to AAC. Hip and vertebral fractures, high phosphate, smoking, hypertension,
      and low osteocalcin could make DM patients prone to AAC. Low levels of high
      density lipoprotein (HDL), high low-density lipoprotein (LDL), high total
      cholesterol/HDL ratio, low bone mineral density (BMD) may be risk factors, but
      the literature is more ambiguous. Body mass index (BMI) does not appear to
      increase risk of AAC. High phosphate levels and low osteocalcin levels seem to be
      biomarkers of AAC in patients with diabetes. However, the association between DM
      and AAC is complicated.

PMID- 29380118
TI  - ALPPS for Hepatocellular Carcinoma Is Associated with Decreased Liver Remnant
      Growth.
AB  - BACKGROUND: Associating liver partition and portal vein ligation for staged
      hepatectomy (ALPPS) has been widely described for colorectal liver metastases
      with insufficient future liver remnant (FLR). However, its role in hepatocellular
      carcinoma (HCC) remains poorly defined and not widely accepted. METHODS: A
      retrospective comparison of clinical data, liver volumetry, histological
      characteristics, and surgical outcomes between nine HCC and four non-HCC patients
      who underwent ALPPS was performed. RESULTS: Patients with HCC were more likely to
      have histological evidence of hepatic fibrosis (HCC vs. non-HCC, 66.7 vs. 0%, p =
      0.049). Baseline demographic and disease characteristics were otherwise
      comparable between both groups. FLR growth after ALPPS-Stage 1 was significantly
      less in HCC patients (HCC vs. non-HCC, 154.5 vs. 251.0 ml, p = 0.012). FLR growth
      was also significantly decreased in patients with hepatic fibrosis (fibrosis vs.
      non-fibrosis, 157.5 vs. 247.5 ml, p = 0.033). There was no difference in post
      hepatectomy liver failure (HCC vs. non-HCC, 28.6 vs. 25%, p = 0.721) or 90-day
      mortality (HCC vs. non-HCC, 11.1 vs. 0%, p = NS). DISCUSSION: In our study, HCC
      patients demonstrated significantly less FLR growth after ALPPS-Stage 1 compared
      to non-HCC patients. Hepatic fibrosis was also found to negatively impact FLR
      growth. When considering suitability for ALPPS, patients with HCC may benefit
      from additional pre-operative assessment of fibrosis.

PMID- 29380119
TI  - Granular cell tumor of the pancreas diagnosed by endoscopic ultrasound-guided
      fine-needle aspiration.
AB  - A 68-year-old woman was referred to our hospital for the treatment of bile duct
      stone, pancreatic tumor, and pancreatic cysts. First, bile duct stone was removed
      using endoscopic retrograde cholangiopancreatography. By abdominal contrast
      enhanced computed tomography, a 12-mm diameter tumor was found in the pancreatic
      body. The tumor was isodense compared with the surrounding pancreatic parenchyma
      in the non-contrast phase and poorly enhanced in the arterial phase; it exhibited
      gradual enhancement from the portal vein phase to the late phase. Numerous
      pancreatic cysts were also observed by contrast-enhanced computed tomography. By
      magnetic resonance imaging, the tumor was hypointense in T1-weighted images,
      isointense in T2-weighted images, and hyperintense in diffusion-weighted images.
      By magnetic resonance cholangiopancreatography, the main pancreatic duct was not
      dilated, and pancreatic cysts communicated with the main pancreatic duct. The
      pancreatic cysts were diagnosed as branch-type intraductal papillary mucinous
      neoplasm. Histopathologic assessment of the specimens obtained by endoscopic
      ultrasound-guided fine-needle aspiration revealed the tumor as benign pancreatic
      granular cell tumor. The patient was followed up without surgical resection. On
      contrast-enhanced computed tomography at 6 months after admission, the tumor did
      not show any changes in diameter or characteristics.

PMID- 29380120
TI  - Altered white matter development in children born very preterm.
AB  - Children born very preterm (VPT) at less than 32 weeks' gestational age (GA) are
      prone to disrupted white matter maturation and impaired cognitive development.
      The aims of the present study were to identify differences in white matter
      microstructure and connectivity of children born VPT compared to term-born
      children, as well as relations between white matter measures with cognitive
      outcomes and early brain injury. Diffusion images and T1-weighted anatomical MR
      images were acquired along with developmental assessments in 31 VPT children
      (mean GA: 28.76 weeks) and 28 term-born children at 4 years of age. FSL's tract
      based spatial statistics was used to create a cohort-specific template and mean
      fractional anisotropy (FA) skeleton that was applied to each child's DTI data.
      Whole brain deterministic tractography was performed and graph theoretical
      measures of connectivity were calculated based on the number of streamlines
      between cortical and subcortical nodes derived from the Desikan-Killiany atlas.
      Between-group analyses included FSL Randomise for voxel-wise statistics and
      permutation testing for connectivity analyses. Within-group analyses between FA
      values and graph measures with IQ, language and visual-motor scores as well as
      history of white matter injury (WMI) and germinal matrix/intraventricular
      haemorrhage (GMH/IVH) were performed. In the children born VPT, FA values within
      major white matter tracts were reduced compared to term-born children. Reduced
      measures of local strength, clustering coefficient, local and global efficiency
      were present in the children born VPT within nodes in the lateral frontal, middle
      and superior temporal, cingulate, precuneus and lateral occipital regions. Within
      group analyses revealed associations in term-born children between FA, Verbal IQ,
      Performance IQ and Full scale IQ within regions of the superior longitudinal
      fasciculus, inferior fronto-occipital fasciculus, forceps minor and forceps
      major. No associations with outcome were found in the VPT group. Global
      efficiency was reduced in the children born VPT with a history of WMI and
      GMH/IVH. These findings are evidence for under-developed and less connected white
      matter in children born VPT, contributing to our understanding of white matter
      development within this population.

PMID- 29380121
TI  - Post mortem single-cell labeling with DiI and immunoelectron microscopy unveil
      the fine structure of kisspeptin neurons in humans.
AB  - Kisspeptin (KP) synthesizing neurons of the hypothalamic infundibular region are
      critically involved in the central regulation of fertility; these cells regulate
      pulsatile gonadotropin-releasing hormone (GnRH) secretion and mediate sex steroid
      feedback signals to GnRH neurons. Fine structural analysis of the human KP system
      is complicated by the use of post mortem tissues. To gain better insight into the
      neuroanatomy of the somato-dendritic cellular compartment, we introduced the
      diolistic labeling of immunohistochemically identified KP neurons using a gene
      gun loaded with the lipophilic dye, DiI. Confocal microscopic studies of primary
      dendrites in 100-um-thick tissue sections established that 79.3% of KP cells were
      bipolar, 14.1% were tripolar, and 6.6% were unipolar. Primary dendrites branched
      sparsely, contained numerous appendages (9.1 +/- 1.1 spines/100 um dendrite), and
      received rich innervation from GABAergic, glutamatergic, and KP-containing
      terminals. KP neuron synaptology was analyzed with immunoelectron microscopy on
      perfusion-fixed specimens. KP axons established frequent contacts and classical
      synapses on unlabeled, and on KP-immunoreactive somata, dendrites, and spines.
      Synapses were asymmetric and the presynaptic structures contained round and
      regular synaptic vesicles, in addition to dense-core granules. Although
      immunofluorescent studies failed to detect vesicular glutamate transporter
      isoforms in KP axons, ultrastructural characteristics of synaptic terminals
      suggested use of glutamatergic, in addition to peptidergic, neurotransmission. In
      summary, immunofluorescent and DiI labeling of KP neurons in thick hypothalamic
      sections and immunoelectron microscopic studies of KP-immunoreactive neurons in
      brains perfusion-fixed shortly post mortem allowed us to identify previously
      unexplored fine structural features of KP neurons in the mediobasal hypothalamus
      of humans.

PMID- 29380122
TI  - Video and accelerometer-based motion analysis for automated surgical skills
      assessment.
AB  - PURPOSE: Basic surgical skills of suturing and knot tying are an essential part
      of medical training. Having an automated system for surgical skills assessment
      could help save experts time and improve training efficiency. There have been
      some recent attempts at automated surgical skills assessment using either video
      analysis or acceleration data. In this paper, we present a novel approach for
      automated assessment of OSATS-like surgical skills and provide an analysis of
      different features on multi-modal data (video and accelerometer data). METHODS:
      We conduct a large study for basic surgical skill assessment on a dataset that
      contained video and accelerometer data for suturing and knot-tying tasks. We
      introduce "entropy-based" features-approximate entropy and cross-approximate
      entropy, which quantify the amount of predictability and regularity of
      fluctuations in time series data. The proposed features are compared to existing
      methods of Sequential Motion Texture, Discrete Cosine Transform and Discrete
      Fourier Transform, for surgical skills assessment. RESULTS: We report average
      performance of different features across all applicable OSATS-like criteria for
      suturing and knot-tying tasks. Our analysis shows that the proposed entropy-based
      features outperform previous state-of-the-art methods using video data, achieving
      average classification accuracies of 95.1 and 92.2% for suturing and knot tying,
      respectively. For accelerometer data, our method performs better for suturing
      achieving 86.8% average accuracy. We also show that fusion of video and
      acceleration features can improve overall performance for skill assessment.
      CONCLUSION: Automated surgical skills assessment can be achieved with high
      accuracy using the proposed entropy features. Such a system can significantly
      improve the efficiency of surgical training in medical schools and teaching
      hospitals.

PMID- 29380123
TI  - Impaired motor control in SIDS infants.

PMID- 29380124
TI  - Investigating the sex-related geometric variation of the human cranium.
AB  - Accurate sexing methods are of great importance in forensic anthropology since
      sex assessment is among the principal tasks when examining human skeletal
      remains. The present study explores a novel approach in assessing the most
      accurate metric traits of the human cranium for sex estimation based on 80
      ectocranial landmarks from 176 modern individuals of known age and sex from the
      Athens Collection. The purpose of the study is to identify those distance and
      angle measurements that can be most effectively used in sex assessment. Three
      dimensional landmark coordinates were digitized with a Microscribe 3DX and
      analyzed in GNU Octave. An iterative linear discriminant analysis of all possible
      combinations of landmarks was performed for each unique set of the 3160 distances
      and 246,480 angles. Cross-validated correct classification as well as
      multivariate DFA on top performing variables reported 13 craniometric distances
      with over 85% classification accuracy, 7 angles over 78%, as well as certain
      multivariate combinations yielding over 95%. Linear regression of these variables
      with the centroid size was used to assess their relation to the size of the
      cranium. In contrast to the use of generalized procrustes analysis (GPA) and
      principal component analysis (PCA), which constitute the common analytical work
      flow for such data, our method, although computational intensive, produced easily
      applicable discriminant functions of high accuracy, while at the same time
      explored the maximum of cranial variability.

PMID- 29380125
TI  - Towards multi-phase postmortem CT angiography in children: a study on a porcine
      model.
AB  - PURPOSE: Multi-phase postmortem computed tomography angiography (MPMCTA) is a
      growing technique, which is standardized for adults. Application of this protocol
      for a children population is not so well defined. Our study aims to adapt the
      adult's protocol to children, using a porcine model. MATERIAL AND METHODS: Three
      groups of 18 pigs were studied, with a weight distribution between 4 and 48 kg.
      Different pump devices were used. Pigs of group I were studied using the
      Virtangio(r) machine, whereas pigs of groups II and III were studied using used
      the Medrad(r) machine. Study of vascular opacification was possible using a semi
      quantitative method based on 26 arterial and 26 venous segments that were
      distributed over the entire body from the cephalic extremity to the posterior
      pawns. RESULTS: While thoracic, abdominal, and pelvic vascular opacification were
      complete for each individual pig in a group, group III showed better vascular
      opacification for the cephalic extremity. This was also true for anterior and
      posterior pawns vascular opacification. Spearman correlation tests showed a
      significant relationship between anthropometric characteristics of pigs,
      injection parameters, and percentage of opacified segments. A higher percentage
      of opacification was obtained for individuals of lower weights, with
      comparatively lower quantities of contrast agent injected. CONCLUSION: Postmortem
      computed tomography angiography (PMCTA) was possible for all the individuals,
      particularly for small weights (4 kg) using the Medrad(r) machine. However,
      further studies are needed to better understand the procedure.

PMID- 29380126
TI  - The new TNM-based staging of breast cancer.
AB  - This review describes the changes that have been implemented in the Tumor-Node
      Metastasis (TNM)-based staging of breast cancers by the new, 8th editions of the
      relevant Union for International Cancer Control (UICC) and American Joint
      Committee on Cancer (AJCC) publications. After giving a background for TNM being
      the common language of cancer staging and related activities like cancer
      treatment and registration, it summarizes not only the changes but reviews some
      highlights important for pathologists, and lists and comments on the differences
      between the publications and diagnostic practices based on them. A section is
      dedicated to the prognostic stages of breast carcinomas introduced in the AJCC
      Cancer Staging Manual, but not mentioned in the UICC TNM classification of
      malignant tumors. A few issues that are not appropriately covered by TNM
      according to the authors' view (e.g., multifocal tumors, larger lymph node
      metastases identified by molecular methods, the heterogeneous prognosis of M1
      defined stage IV disease) close the review with the final thoughts raising the
      vision of a potential loss of the common staging language.

PMID- 29380127
TI  - Pathologist's assistant (PathA) and his/her role in the surgical pathology
      department: a systematic review and a narrative synthesis.
AB  - In recent decades, various highly qualified individuals have increasingly
      performed tasks that have historically been handled by physicians with the aim of
      reducing their workload. Over time, however, these "physician assistants" or
      "physician extenders" have gained more and more responsibilities, showing that
      specific tasks can be performed equally skilfully by specialised health care
      professionals. The pathologist's assistant (PathA) is a highly qualified
      technician who works alongside the pathologist and is responsible for the
      grossing and autopsies. This profession was developed in the USA, with formal
      training programmes starting in 1970 when Dr. Kinney, director of the Department
      of Pathology of Duke University, Durham, NC, started the first dedicated course.
      Most institutes in the USA and Canada currently employ these technical personnel
      for grossing, and numerous papers published over the years demonstrate the
      quality of the assistance provided by the PathA, which is equal to or sometimes
      even better than the performance of pathologists. The PathA can be employed to
      carry out a wide range of tasks to assist the pathologist, such as grossing (the
      description and reduction of surgical specimens), judicial autopsies and
      administrative and supervisory practices within the laboratory or assistance in
      research, although the diagnosis is always the pathologist's responsibility.
      Since this role has already been consolidated in North America, part of the
      relevant literature is altogether out of date. However, the situation is
      different in Europe, where there is an increasing interest in PathA, mainly
      because of the benefits of their inclusion in anatomic pathology laboratories. In
      the UK, biomedical scientists (BMS, the British equivalent of PathA) are involved
      in many tasks both in surgical pathology and in cytopathology, which are
      generally performed by medically trained staff. Several papers have been recently
      published to highlight the role of BMS with the broader public. This report aimed
      to conduct a systematic review of all the articles published about the PathA/BMS
      and to perform a narrative synthesis. The results may contribute to the evidence
      for including the PAthA/BMS within a surgical pathology laboratory organisation.

PMID- 29380128
TI  - Fexapotide triflutate: results of long-term safety and efficacy trials of a novel
      injectable therapy for symptomatic prostate enlargement.
AB  - PURPOSE: These studies were undertaken to determine if fexapotide triflutate 2.5
      mg transrectal injectable (FT) has significant long-term (LT) safety and efficacy
      for the treatment of benign prostatic hyperplasia (BPH). METHODS: Two placebo
      controlled double-blind randomized parallel group trials with 995 BPH patients at
      72 sites treated 3:2 FT:placebo, with open-label FT crossover (CO) re-injection
      in 2 trials n = 344 and long-term follow-up (LF) 2-6.75 years (mean 3.58 years,
      median 3.67 years; FT re-injection CO mean 4.27 years, median 4.42 years) were
      evaluated. 12 months post-treatment patients elected no further treatment,
      approved oral medications, FT, or interventional treatment. Primary endpoint
      variable was change in Symptom Score (IPSS) at 12 months and at LF. CO primary co
      endpoints were 3-year incidence of (1) surgery for BPH in FT treated CO patients
      versus patients crossed over to oral BPH medications and (2) surgery or acute
      urinary retention in FT-treated CO placebo patients versus placebo patients
      crossed over to oral BPH medications. 28 CO secondary endpoints assessed surgical
      and symptomatic outcomes in FT reinjected patients versus conventional BPH
      medication CO and control subgroups at 2 and 3 years. RESULTS: FT injection had
      no significant safety differences from placebo. LF IPSS change from baseline was
      higher in FT treated patients compared to placebo (median FT group improvement -
      5.2 versus placebo - 3.0, p < 0.0001). LF incidence of AUR (1.08% p = 0.0058) and
      prostate cancer (PCa) (1.1% p = 0.0116) were both reduced in FT treated patients.
      LF incidence of intervention for BPH was reduced in the FT group versus oral BPH
      medications (8.08% versus 27.85% at 3 years, p < 0.0001). LF incidence of
      intervention or AUR in placebo CO group with FT versus placebo CO group with oral
      medications was reduced (6.07% versus 33.3% at 3 years, p < 0.0001). 28/28
      secondary efficacy endpoints were reached in LF CO re-injection studies.
      CONCLUSIONS: FT 2.5 mg is a safe and effective transrectal injectable for LT
      treatment of BPH. FT treated patients also had reduced need for BPH intervention,
      and reduced incidence of PCa and AUR.

PMID- 29380129
TI  - Tumor complexity and the impact on MIC and trifecta in robot-assisted partial
      nephrectomy: a multi-center study of over 500 cases.
AB  - PURPOSE: To demonstrate the surgical feasibility of robot-assisted partial
      nephrectomy for complex renal masses with comparison of low/intermediate risk
      versus high-risk tumors according to the PADUA score. METHODS: Since 2008, 538
      robot-assisted partial nephrectomies were performed at three German robotic
      centers. Both the MIC (margin, ischemia, complications) criteria and trifecta
      were applied. RESULTS: 60.1% of the tumors were of low and intermediate
      complexity (PADUA score 6-9, n = 326, group A), while 39.9% were highly complex
      (n = 212, score >= 10, B). Median clinical tumor size was 28 in A versus 37 mm in
      B (p < 0.001). There was no significant difference in terms of operative time
      (160 vs. 163 min, p = 0.20); ischemia time was slightly longer for B (11 vs. 12
      min, p < 0.001). There were no significant differences for intra- (3.4%, A, vs.
      6.6%, B, p = 0.10) or postoperative (21.5%, A, vs. 25.5%, B, p = 0.30)
      complication rates. There was a median eGFR decrease of - 9.4 (A) versus - 15.1
      (B) ml/min (p < 0.001) on discharge. Histopathology revealed an R1 margin rate of
      3.4% for the low/intermediate versus 6.1% for the high complexity group (p =
      0.14). MIC criteria were fulfilled in 81.9% (A) versus 75.5% (B, p = 0.11) and
      trifecta criteria in 74.2% (A) versus 68.93% (B, p = 0.26). CONCLUSIONS:
      Complication rates, histopathology results as well as quality criteria as
      indicated by MIC and trifecta were similar for high and low complexity groups.
      Therefore, robot-assisted partial nephrectomy is a safe and feasible option also
      in highly complex tumors.

PMID- 29380130
TI  - Prostate cancer detection in patients with prior negative biopsy undergoing
      cognitive-, robotic- or in-bore MRI target biopsy.
AB  - PURPOSE: To evaluate the detection rate among three different targeted biopsy
      approaches of robot-assisted MRI/TRUS fusion (RA-TB), mpMRI in-bore (MRGB),
      cognitive fusion guidance biopsy (COG-TB) for the detection of prostate cancer
      (PC) and clinically significant PC (csPC). METHODS: Between 2014 and 2016, 156
      patients with a lesion on mpMRI, performed in accordance with ESUR guidelines,
      due to cancer suspicion or on-going cancer suspicion after prior negative
      prostate biopsy, underwent targeted biopsy with RA-TB, MRGB or COG-TB. All
      lesions were rated according to PI-RADS v2. We compared detection rates between
      techniques. Models were constructed to predict the detection of overall PC and
      csPC and using a 1000 boot-strap sample. RESULTS: In the all cohort, 73, 45 and
      38 patients underwent RA-TB, MRGB or COG-TB, respectively. Overall PC was found
      in 39 (52.42%), 23 (51.11%) and 11 (28.95%) (p = 0.04) patients of RA-TB, MRGB
      and COG-TB arm, respectively. As concerning the detection of csPC, it was found
      in 26 (35.62%),18 (40.0%) and 9 (23.68%) patients of RA-TB, MRGB and COG-TB arm
      (p = 0.27). Model 1 showed that RA-TB [OR: 10.08 (95% CI 1.95-51.97); p < 0.01]
      and MRGB [OR: 12.88 (95% CI 2.36-70.25); p < 0.01] were associated with overall
      PC detection in TB, while only MRGB was associated with csPC at TB (model 2) [OR:
      5.72; (95% CI 1.40-23.35); p < 0.01]. The c-index for model 1 and model 2 was
      0.86 and 0.85, respectively. We did not report significant complications between
      groups. CONCLUSION: In-bore biopsy and MRI/TRUS fusion-guided biopsy showed
      greater accuracy in detecting PC compared to cognitive fusion as modeled in a
      newly established normogram.

PMID- 29380131
TI  - Increasing the size of ureteral access sheath during retrograde intrarenal
      surgery improves surgical efficiency without increasing complications.
AB  - PURPOSE: To directly compare intraoperative and post-operative outcomes and
      complications between three groups undergoing ureteroscopy: no ureteral access
      sheath, 12/14 Fr and larger 14/16 Fr ureteral access sheaths (UAS). METHODS: We
      retrospectively reviewed demographic, pre-operative, intraoperative, and post
      operative data of 257 patients who underwent ureteroscopy for nephrolithiasis by
      a single surgeon from January 2013 through July 2015. Patients were separated
      into three groups: no UAS, a 12/14 Fr UAS, or 14/16 Fr UAS. Outcomes included
      differences in stone-free rate, post-procedure-related events (PRE), ureteral
      injury rate (measured by early post-operative hydronephrosis), and post-operative
      complications. RESULTS: A UAS was used in 65.4% (168/257) patients, with 73.8%
      (124/168) utilizing a 12/14 Fr UAS and 26.2% (44/168) utilizing a 14/16 Fr UAS.
      Those patients in whom a 14/16 Fr UAS was employed had greater stone burden
      compared to the 12/14 Fr UAS group (180.8 +/- 18.0 vs. 104 +/- 9.1 mm2, p <
      0.001). When comparing 12/14 Fr and 14/16 Fr ureteral access sheaths, there was
      no significant difference in ureteral injury rate, complications (10.5 vs. 11.4%,
      respectively; p = 0.87), or overall stone-free rate (78.1 vs. 81.3%, p = 0.70).
      The mean amount of stone burden treated per minute of operative time was more
      than 30% higher in the 14/16 Fr UAS group compared to 12/14 Fr UAS group (2.11
      vs. 1.62 mm2/min; p = 0.01). CONCLUSION: The use of a 14/16 Fr UAS allows for
      similar stone-free rate and improved operative efficiency with no increased risk
      of ureteral injury or post-operative complications when compared to the 12/14 Fr
      UAS.

PMID- 29380133
TI  - Non-urgent use of emergency departments: populations most likely to overestimate
      illness severity.
AB  - Patients' overestimation of their illness severity appears to contribute to the
      national epidemic of emergency department (ED) overcrowding. This study aims to
      elucidate which patient populations are more likely to have a higher estimation
      of illness severity (EIS). The investigator surveyed demographic factors of all
      non-urgent patients at an academic ED. The patients and physicians were asked to
      estimate the patients' illness severity using a 1-10 scale with anchors. The
      difference of these values was taken and compared across patient demographic
      subgroups using a 2-sample t-test. One hundred and seventeen patients were
      surveyed. The mean patient EIS was 5.22 (IQR 4), while the mean physician EIS was
      less severe at 7.57 (IQR 3), a difference of 2.35 (p < 0.0001). Patient subgroups
      with the highest EIS compared to the physicians' EIS include those who were self
      referred (difference of 2.65, p = 0.042), with income <= $25,000 (difference of
      2.96, p = 0.004), with less than a college education (difference of 2.83, p =
      0.018), and with acute-on-chronic musculoskeletal pain (difference of 4.17, p =
      0.001). If we assume the physicians' EIS is closer to the true illness severity,
      patients with lower socioeconomic status, lower education status, who were self
      referred, and who suffered from acute-on-chronic musculoskeletal pain are more
      likely to overestimate their illness severity and may contribute to non-urgent
      use of the ED. They may benefit from further education or resources for care to
      prevent ED misuse. The large difference of acute-on-chronic musculoskeletal pain
      may reflect a physician's bias to underestimate the severity of a patients'
      illness in this particular population.

PMID- 29380132
TI  - Biological response to self-etch adhesive after partial caries removal in rats.
AB  - OBJECTIVES: The purposes of this study were to evaluate a model of slow caries
      progression and to investigate the performance of a self-etch adhesive system for
      partial caries removal. MATERIALS AND METHODS: Rat molars were infected with
      Streptococcus sobrinus 6715 culture. Different time points were analyzed: days
      78, 85, and 95 (+/- 2). After this, the samples were processed for morphological
      analysis. Additionally, the first molars were restored with zinc oxide and
      eugenol (IRMTM; Dentsply; Brazil) or adhesive system (Clearfil SE BondTM; Kuraray
      Medical; Japan) 78 days after caries induction. After, 3 or 15 days post
      treatment, the animals were euthanized, and their mandibles were processed for
      morphological analysis, classified by means of scores, and submitted to
      statistical analysis. Subsequently, immunohistochemical analysis was performed
      for osteonectin (OSN) and transforming growth factor-beta1 (TGF-beta1)
      expression. RESULTS: According to the caries induction model used, on day 95
      greater inflammatory infiltration (p < 0.001), and more extensive degradation of
      secondary/primary dentin were demonstrated than on day 78 (p < 0.05).
      Furthermore, the restorative materials presented similar performance (p > 0.05)
      and proved to be fundamental to control the carious lesion. The TGF-beta1 and OSN
      were shown to be active during the caries process. CONCLUSIONS: The slow caries
      lesion model was feasible for morphological analysis of the dentin-pulp complex.
      The self-etch adhesive system triggered no acute inflammatory infiltration or
      pulp necrosis, instead it seemed to stimulate early pulp repair. CLINICAL
      RELEVANCE: Clearfil SE BondTM applied directly on caries-affected dentin did not
      predispose to pulp inflammation; instead, it appeared to provide early biological
      benefits.

PMID- 29380134
TI  - New insight into defining the lakes of the southern Baltic coastal zone.
AB  - There exist many classification systems of hydrographic entities such as lakes
      found along the coastlines of seas and oceans. Each system has its advantages and
      can be used with some success in the area of protection and management. This
      paper aims to evaluate whether the studied lakes are only coastal lakes or rather
      bodies of water of a completely different hydrological and hydrochemical nature.
      The attempt to create a new classification system of Polish coastal lakes is
      related to the incompleteness of lake information in existing classifications.
      Thus far, the most frequently used are classifications based solely on lake basin
      morphogenesis or hydrochemical properties. The classifications in this paper are
      based not only on the magnitude of lake water salinity or hydrochemical analysis
      but also on isolation from the Baltic Sea and other sources of water. The key
      element of the new classification system for coastal bodies of water is a
      departure from the existing system used to classify lakes in Poland and the
      introduction of ion-"tracking" methods designed to identify anion and cation
      distributions in each body of water of interest. As a result of the work, a new
      classification of lakes of the southern Baltic Sea coastal zone was created.
      Featured objects such as permanently brackish lakes, brackish lakes that may turn
      into freshwater lakes from time to time, freshwater lakes that may turn into
      brackish lakes from time to time, freshwater lakes that experience low levels of
      salinity due to specific incidents, and permanently freshwater lakes. The authors
      have adopted 200 mg Cl- dm-3 as a maximum value of lake water salinity. There are
      many conditions that determine the membership of a lake to a particular group,
      but the most important is the isolation lakes from the Baltic Sea. Changing a
      condition may change the classification of a lake.

PMID- 29380135
TI  - Significance of bacterial culturing of prophylactic drainage fluid in the early
      postoperative period after liver resection for predicting the development of
      surgical site infections.
AB  - PURPOSES: The relationship between the results of bacterial drainage fluid
      cultures in the early postoperative period after liver resection and the
      development of surgical site infections (SSIs) is unclear. We evaluated the
      diagnostic value of bacterial cultures of drainage fluid obtained on
      postoperative day (POD) 1 after liver resection. METHODS: The cases of all
      consecutive patients who underwent elective liver resection from January 2014 to
      December 2016 were analyzed. The association between a positive culture result
      and the development of SSIs was analyzed. RESULTS: A total of 195 consecutive
      patients were studied. Positive drainage fluid cultures were obtained in 6
      patients (3.1%). A multivariate analysis revealed that a positive drainage fluid
      culture was an independent risk factor for SSIs (odds ratio: 8.04, P = 0.035),
      and combined resection of the gastrointestinal tract was a risk factor for a
      positive drainage fluid culture (P = 0.006). Among the patients who did not
      undergo procedures involving the gastrointestinal tract, there was no association
      between drainage fluid culture positivity and SSIs. CONCLUSIONS: The detection of
      positive culture results for drainage fluid collected on POD 1 after liver
      resection was associated with SSIs. However, among patients who did not undergo
      procedures involving the gastrointestinal tract, it was not a predictor of SSIs.

PMID- 29380136
TI  - National survey of de novo malignancy after solid organ transplantation in Japan.
AB  - PURPOSE: In Japan, there have been no national surveys on the incidence of de
      novo malignancy after solid organ transplantation, which is one of the leading
      causes of death in transplant recipients. METHODS: A questionnaire was
      distributed to institutions that perform solid organ transplantation in Japan,
      and clinical information was collected from patients who underwent
      transplantation between 2001 and 2010 and who exhibited de novo malignancies.
      RESULTS: Nine thousand two hundred ten solid organ transplants (kidney, 49.9%;
      liver, 45.9%; heart, 0.9%; lung, 1.2%; pancreas, 1.9%; small intestine, 0.2%)
      were performed. Four hundred seventy-nine (5.2%) cases of de novo malignancy were
      identified. The transplanted organs of the patients included the kidney (n = 479,
      54.8%), liver (n = 186, 38.8%), heart (n = 5, 0.1%), lung (n = 18, 3.8%),
      pancreas (n = 9, 1.9%), and small intestine (n = 1, 0.02%). The most common
      malignancies were post-transplant lymphoproliferative disorder (n = 87) and
      cancers of the kidney (n = 43), stomach (n = 41), large intestine (n = 41), and
      lung (n = 36). CONCLUSIONS: This is the first national survey of the incidence of
      de novo malignancy in Japan. Further study is required to identify the risk of de
      novo malignancy in organ transplant recipients in comparison to the general
      population, namely the standardized incidence ratio.

PMID- 29380137
TI  - Automated segmentation and detection of increased uptake regions in bone
      scintigraphy using SPECT/CT images.
AB  - PURPOSE: To develop a method for automated detection of highly integrated sites
      in SPECT images using bone information obtained from CT images in bone
      scintigraphy. METHODS: Bone regions on CT images were first extracted, and bones
      were identified by segmenting multiple regions. Next, regions corresponding to
      the bone regions on SPECT images were extracted based on the bone regions on CT
      images. Subsequently, increased uptake regions were extracted from the SPECT
      image using thresholding and three-dimensional labeling. Last, the ratio of
      increased uptake regions to all bone regions was calculated and expressed as a
      quantitative index. To verify the efficacy of this method, a basic assessment was
      performed using phantom and clinical data. RESULTS: The results of this
      analytical method using phantoms created by changing the radioactive
      concentrations indicated that regions of increased uptake were detected
      regardless of the radioactive concentration. Assessments using clinical data
      indicated that detection sensitivity for increased uptake regions was 71% and
      that the correlation between manual measurements and automated measurements was
      significant (correlation coefficient 0.868). CONCLUSION: These results suggested
      that automated detection of increased uptake regions on SPECT images using bone
      information obtained from CT images would be possible.

PMID- 29380138
TI  - Relationship between collateral circulation and myocardial viability of 18F-FDG
      PET/CT subtended by chronic total occluded coronary arteries.
AB  - OBJECTIVE: To analyze the relationship between the collateral flow of coronary
      chronic total occlusion (CTO) and myocardial viability detected by 18F
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) imaging. METHODS: A prospective analysis of 104 patients diagnosed by
      coronary angiography. All patients underwent resting myocardial perfusion imaging
      and PET/CT within 1 week. The collateral circulation was graded with Rentrop
      classification as no or poor collateral circulation in 16 CTO vessels, moderate
      collateral circulation in 34 CTO vessels, and good collateral circulation in 69
      CTO vessels. Myocardial viability was determined with myocardial perfusion
      imaging and PET. The patterns were interpreted as mismatch, match and normal
      perfusion and 18F-FDG uptake. RESULTS: There was no significant correlation
      between the severity and extent of perfusion defect, myocardial viability and
      collateral circulation grade. The myocardial viability was normal in mild and
      moderate hypokinetic regions and decreased in severe hypokinetic and akinesis
      dyskinesis regions. The presence of collateral circulation was a sensitive (89%)
      but not a specific (31%) sign of myocardial viability. CONCLUSIONS: In patients
      with CTO, collateral circulation does not seem to be an effective way for
      predicting myocardial viability. Further analysis of PET patterns of viable
      myocardium is needed to guide further revascularization and predict functional
      improvement and survival benefit.

PMID- 29380139
TI  - Involuntary and voluntary recall of musical memories: A comparison of temporal
      accuracy and emotional responses.
AB  - Comparisons between involuntarily and voluntarily retrieved autobiographical
      memories have revealed similarities in encoding and maintenance, with differences
      in terms of specificity and emotional responses. Our study extended this research
      area into the domain of musical memory, which afforded a unique opportunity to
      compare the same memory as accessed both involuntarily and voluntarily.
      Specifically, we compared instances of involuntary musical imagery (INMI, or
      "earworms")-the spontaneous mental recall and repetition of a tune-to deliberate
      recall of the same tune as voluntary musical imagery (VMI) in terms of recall
      accuracy and emotional responses. Twenty participants completed two 3-day tasks.
      In an INMI task, participants recorded information about INMI episodes as they
      occurred; in a VMI task, participants were prompted via text message to
      deliberately imagine each tune they had previously experienced as INMI. In both
      tasks, tempi of the imagined tunes were recorded by tapping to the musical beat
      while wearing an accelerometer and additional information (e.g., tune name,
      emotion ratings) was logged in a diary. Overall, INMI and VMI tempo measurements
      for the same tune were strongly correlated. Tempo recall for tunes that have
      definitive, recorded versions was relatively accurate, and tunes that were
      retrieved deliberately (VMI) were not recalled more accurately in terms of tempo
      than spontaneous and involuntary instances of imagined music (INMI). Some
      evidence that INMI elicited stronger emotional responses than VMI was also
      revealed. These results demonstrate several parallels to previous literature on
      involuntary memories and add new insights on the phenomenology of INMI.

PMID- 29380141
TI  - A close-up view of the wood cell wall ultrastructure and its mechanics at
      different cutting angles by atomic force microscopy.
AB  - MAIN CONCLUSION: AFM measurements on spruce sample cross-sections reveal that the
      structural appearance of the S2 layer changes from a network structure to a
      concentric lamellar texture depending on the cutting angle. The structural
      assembly of wood constituents within the secondary cell wall has been subject of
      numerous studies over the last decades, which has resulted in contradicting
      models on the spatial arrangement and orientation of the wood macromolecules.
      Here, we use multichannel atomic force microscopy by means of quantitative
      imaging, to gain new insights into the macromolecular assembly. Cross-sections of
      spruce wood, which had been cut at different angles ranging from 0 degrees  to 30
      degrees  were investigated. Strikingly, depending on the cutting angle, the
      structural appearance of the S2 layer changed from a network-like structure to a
      distinct concentric lamellar texture. This makes us conclude that the often
      visualized lamellar organization of the secondary cell wall is not the
      consequence of a continuous inherent ring pattern, but rather a result of the
      specific surface cross-section appearance of cellulose aggregates at larger
      cutting angles. By analyzing the recorded force distance curves in every pixel, a
      nano-mechanical characterization of the secondary cell wall was conducted.
      Substantially lower indentation modulus values were obtained compared to
      nanoindentation values reported in the literature. This is potentially due to a
      smaller interaction volume of the probe with a by far less deep indentation.

PMID- 29380142
TI  - Therapeutic Inertia and Treatment Intensification.
AB  - PURPOSE OF REVIEW: This review aims to emphasize how therapeutic inertia, the
      failure of clinicians to intensify treatment when blood pressure rises or remains
      above therapeutic goals, contributes to suboptimal blood pressure control in
      hypertensive populations. RECENT FINDINGS: Studies reveal that the therapeutic
      inertia is quite common and contributes to suboptimal blood pressure control.
      Quality improvement programs and standardized approaches to support
      antihypertensive treatment intensification are ways to combat therapeutic
      inertia. Furthermore, programs that utilize non-physician medical professionals
      such as pharmacists and nurses demonstrate promise in mitigating the effects of
      this important problem. Therapeutic inertia impedes antihypertensive management
      and requires a broad effort to reduce its effects. There is an ongoing need for
      renewed focus and research in this area to improve hypertension control.

PMID- 29380144
TI  - Contemporary Perspectives in Durable Mechanical Circulatory Support: What Did We
      Learn in the Last 3 Years?
AB  - PURPOSE OF REVIEW: In this paper, we will review developments in the field of
      durable mechanical circulatory support over the past 3 years. RECENT FINDINGS:
      The role of left ventricular assist device (LVAD) placement in non-inotrope
      dependent ambulatory heart failure patients remains controversial in light of
      recent clinical trials. New devices are on the horizon for destination therapy in
      advanced heart failure patients. The concept of hemocompatibility and the
      calculation of hemocompatibility scores represent a novel approach to common
      adverse events. Recent research in mechanical circulatory support has impacted
      our approach to durable LVAD therapy and set the stage for further advancements
      in the field.

PMID- 29380143
TI  - Biomarker responses of Peromyscus leucopus exposed to lead and cadmium in the
      Southeast Missouri Lead Mining District.
AB  - Biomarker responses and histopathological lesions have been documented in
      laboratory mammals exposed to elevated concentrations of lead and cadmium. The
      exposure of white-footed mice (Peromyscus leucopus) to these metals and the
      potential associated toxic effects were examined at three contaminated sites in
      the Southeast Missouri Lead Mining District and at a reference site in MO, USA.
      Mice from the contaminated sites showed evidence of oxidative stress and reduced
      activity of red blood cell delta-aminolevulinic acid dehydratase (ALAD).
      Histological examinations of the liver and kidney, cytologic examination of blood
      smears, and biomarkers of lipid peroxidation and DNA damage failed to show
      indications of toxic effects from lead. The biomagnification factor of cadmium
      (hepatic concentration/soil concentration) at a site with a strongly acid soil
      was 44 times the average of the biomagnification factors at two sites with
      slightly alkaline soils. The elevated concentrations of cadmium in the mice did
      not cause observable toxicity, but were associated with about a 50% decrease in
      expected tissue lead concentrations and greater ALAD activity compared to the
      activity at the reference site. Lead was associated with a decrease in
      concentrations of hepatic glutathione and thiols, whereas cadmium was associated
      with an increase. In addition, to support risk assessment efforts, we developed
      linear regression models relating both tissue lead dosages (based on a previously
      published a laboratory study) and tissue lead concentrations in Peromyscus to
      soil lead concentrations.

PMID- 29380145
TI  - Performance Assessment of Pharmacotherapy: Results from a Content Validity Survey
      of the Psychopharmacotherapy-Structured Clinical Observation (P-SCO) Tool.
AB  - OBJECTIVE: The Psychopharmacotherapy-Structured Clinical Observation (P-SCO) tool
      is designed to assess performance of a medication management visit and to enhance
      feedback. Prior research indicated that the P-SCO was feasible to implement in a
      resident clinic and generated behaviorally specific, high-quality feedback. This
      research also highlighted problems with some of the instrument's items. This
      study seeks to improve the items. METHODS: The authors initially revised the P
      SCO items based on the problems identified by a prior study. Next, these items
      were iteratively modified by experts in clinical pharmacotherapy and educational
      assessment. Forty-five items emerged. Finally, faculty attending an annual
      department education retreat rated each item on its relevance (4-point scale) and
      provided comments on how the item might be revised. For final inclusion, an item
      must have met a quantitative threshold (i.e., content validity index equal to or
      greater than 0.8 and the lower end of the asymmetric confidence interval equal to
      or greater than 3.0) and received comments that were supportive. RESULTS: Forty
      one of the 45 items had strong quantitative support. However, the comments
      endorsed lumping a number of items in order to decrease overlap between items and
      to shorten the instrument. This process resulted in the further elimination of 15
      items. CONCLUSIONS: The revised 26-item P-SCO builds upon prior evidence of
      feasibility and utility and now possesses additional evidence of content
      validity. The use of the tool should enhance feedback and improve the capacity of
      educational programs to assess performance.

PMID- 29380146
TI  - Pseudomalignant osteoblastoma of the odontoid process.
AB  - INTRODUCTION: The anterior elements of the spine, particularly the odontoid
      processes, are a rare location for osteoblastomas. Pseudomalignant osteoblastomas
      are themselves rare histologic types and are also extremely rare in this
      location. Most osteoblastomas are Enneking stage 2 lesions; less frequently, they
      can be more aggressive with extra-capsular extension (Enneking stage 3). En bloc
      resection is recommended for aggressive lesions, but the literature is less clear
      regarding the approach to stage 2 tumors, particularly those with pseudomalignant
      histologic features. CASE REPORT: A 6-year-old male child presented with a type
      III pathologic fracture of the odontoid. The fracture healed but upon 6-month
      follow-up CT scanning, an expansile lesion was detected. Surgical biopsy revealed
      an osteoblastoma which was treated with intralesional excision. Meanwhile, the
      excised specimen showed histological features of a pseudomalignant osteoblastoma.
      Despite this diagnosis, no further treatment was undertaken. At a 10-year follow
      up, the patient was free from pain and had full range of motion of the cervical
      spine; no recurrence was detected. CONCLUSION: This unique case of odontoid
      osteoblastoma illustrates that malignant behavior may not be predicted only by
      the presence of pseudomalignant features on histology.

PMID- 29380147
TI  - Meet the ExpertsTM.

PMID- 29380148
TI  - Real-time ultrasound-MRI fusion image virtual navigation for locating intraspinal
      tumour in a pregnant woman.
AB  - BACKGROUND: Standard fluoroscopic guidance (C-arm fluoroscopy) has been routinely
      used for intraoperative localization of spinal level for surgical removal of
      intraspinal tumour, while it is not suitable for selected patients, e.g. pregnant
      women, who need to avoid radiation exposure. Fusion imaging of real-time
      ultrasound (US) and magnetic resonance imaging (MRI) is a radiation-free
      technique which has been reported to have good localization accuracy in managing
      several conditions. CLINICAL PRESENTATION: A 37-year-old pregnant patient,
      presented with a progressively aggravating lower back pain for 20 days and was
      incapable of lying supine with lower extremities swelling for 1 week, was
      referred to our hospital in her 18th week of gestation. Lumbar MRI identified an
      L1 level intraspinal lesion, and surgery was planned. To avoid the ionizing
      radiation generated by fluoroscopy, volume navigation technique (VNT) based
      fusion imaging of US and MRI was used to localize the intraspinal lesion, which
      was removed entirely via minimally invasive interlaminar approach. Pathological
      examination confirmed the diagnosis of ependymoma of the conus medullaris. Her
      symptoms were largely relieved after the operation, and a healthy baby was
      delivered at the 40th week of pregnancy. CONCLUSION: We presented the first case
      of using VNT based fusion imaging of real-time US/MRI to guide the surgical
      resection of an intraspinal tumour. Future study with larger patient number is
      needed to validate this technique as an alternative to fluoroscopy in patients
      who need to avoid radiation exposure.

PMID- 29380149
TI  - Litter size reduction accentuates maternal care and alters behavioral and
      physiological phenotypes in rat adult offspring.
AB  - Maternal behavior has a substantial impact on the behavioral, endocrine, and
      neural development of the pups. This study investigated the effect of altering
      the neonatal nutritional environment by modifying the litter size on maternal
      care and anxiety- and fear-like behaviors in rats during adulthood. On postnatal
      day (PND) 2, litters were adjusted to a small litter (SL) size of three pups per
      dam or normal litter (NL) size of 12 pups per dam. Maternal behaviors were scored
      daily during lactation (PND2-21). The weight gain, food intake, adiposity, and
      biochemical landmarks of offspring rats were evaluated. On PND60, performances in
      the open field, elevated plus-maze (EPM), and fear conditioning test were
      measured. The reduction of the litter size enhanced maternal care in lactating
      rats, increasing the arched-back posture and licking pups. SL offspring exhibited
      accelerated weight gain, hyperphagia, increased visceral fat mass, dyslipidemia,
      and hyperleptinemia in adulthood. The SL offspring of both sexes showed an
      increase in the anti-thigmotactic effect in the open field, an intact anxious
      phenotype in the EPM, and a decrease in the time spent freezing during the fear
      conditioning test, compared to NL. The neonatal environment as determined by
      litter size plays a crucial role in programming the adult metabolic phenotype as
      well as behavioral responses to stressful stimuli, with an impact on anxiety-like
      and fear behaviors. These behavioral changes in offspring may be, at least in
      part, a result of increased maternal care.

PMID- 29380150
TI  - Dynamic metabolic control: towards precision engineering of metabolism.
AB  - Advances in metabolic engineering have led to the synthesis of a wide variety of
      valuable chemicals in microorganisms. The key to commercializing these processes
      is the improvement of titer, productivity, yield, and robustness. Traditional
      approaches to enhancing production use the "push-pull-block" strategy that
      modulates enzyme expression under static control. However, strains are often
      optimized for specific laboratory set-up and are sensitive to environmental
      fluctuations. Exposure to sub-optimal growth conditions during large-scale
      fermentation often reduces their production capacity. Moreover, static control of
      engineered pathways may imbalance cofactors or cause the accumulation of toxic
      intermediates, which imposes burden on the host and results in decreased
      production. To overcome these problems, the last decade has witnessed the
      emergence of a new technology that uses synthetic regulation to control
      heterologous pathways dynamically, in ways akin to regulatory networks found in
      nature. Here, we review natural metabolic control strategies and recent
      developments in how they inspire the engineering of dynamically regulated
      pathways. We further discuss the challenges of designing and engineering dynamic
      control and highlight how model-based design can provide a powerful formalism to
      engineer dynamic control circuits, which together with the tools of synthetic
      biology, can work to enhance microbial production.

PMID- 29380151
TI  - Membrane engineering via trans-unsaturated fatty acids production improves
      succinic acid production in Mannheimia succiniciproducens.
AB  - Engineering of microorganisms to produce desired bio-products with high titer,
      yield, and productivity is often limited by product toxicity. This is also true
      for succinic acid (SA), a four carbon dicarboxylic acid of industrial importance.
      Acid products often cause product toxicity to cells through several different
      factors, membrane damage being one of the primary factors. In this study, cis
      trans isomerase from Pseudomonas aeruginosa was expressed in Mannheimia
      succiniciproducens to produce trans-unsaturated fatty acid (TUFA) and to
      reinforce the cell membrane of M. succiniciproducens. The engineered strain
      showed significant decrease in membrane fluidity as production of TUFA enabled
      tight packing of fatty acids, which made cells to possess more rigid cell
      membrane. As a result, the membrane-engineered M. succiniciproducens strain
      showed higher tolerance toward SA and increased production of SA compared with
      the control strain without membrane engineering. The membrane engineering
      approach employed in this study will be useful for increasing tolerance to, and
      consequently enhancing production of acid products.

PMID- 29380153
TI  - Rational design of a synthetic Entner-Doudoroff pathway for enhancing glucose
      transformation to isobutanol in Escherichia coli.
AB  - Isobutanol as a more desirable biofuel has attracted much attention. In our
      previous work, an isobutanol-producing strain Escherichia coli LA09 had been
      obtained by rational redox status improvement under guidance of the genome-scale
      metabolic model. However, the low transformation from sugar to isobutanol is a
      limiting factor for isobutanol production by E. coli LA09. In this study, the
      intracellular metabolic profiles of the isobutanol-producing E. coli LA09 with
      different initial glucose concentrations were investigated and the metabolic
      reaction of fructose 6-phosphate to 1, 6-diphosphate fructose in glycolytic
      pathway was identified as the rate-limiting step of glucose transformation. Thus,
      redesigned carbon catabolism was implemented by altering flux of sugar
      metabolism. Here, the heterologous Entner-Doudoroff (ED) pathway from Zymomonas
      mobilis was constructed, and the adaptation of upper and lower parts of ED
      pathway was further improved with artificial promoters to alleviate the
      accumulation of toxic intermediate metabolite 2-keto-3-deoxy-6-phospho-gluconate
      (KDPG). Finally, the best isobutanol-producing E. coli ED02 with higher glucose
      transformation and isobutanol production was obtained. In the fermentation of
      strain E. coli ED02 with 45 g/L initial glucose, the isobutanol titer, yield and
      average producing rate were, respectively, increased by 56.8, 47.4 and 88.1% to
      13.67 g/L, 0.50 C-mol/C-mol and 0.456 g/(L * h) in a shorter time of 30 h,
      compared with that of the starting strain E. coli LA09.

PMID- 29380154
TI  - Development and Validation of Segmentation Method for Lung Cancer Volumetry on
      Chest CT.
AB  - The set of criteria called Response Evaluation Criteria In Solid Tumors (RECIST)
      is used to evaluate the remedial effects of lung cancer, whereby the size of a
      lesion can be measured in one dimension (diameter). Volumetric evaluation is
      desirable for estimating the size of a lesion accurately, but there are several
      constraints and limitations to calculating the volume in clinical trials. In this
      study, we developed a method to detect lesions automatically, with minimal
      intervention by the user, and calculate their volume. Our proposed method, called
      a spherical region-growing method (SPRG), uses segmentation that starts from a
      seed point set by the user. SPRG is a modification of an existing region-growing
      method that is based on a sphere instead of pixels. The SPRG method detects
      lesions while preventing leakage to neighboring tissues, because the sphere is
      grown, i.e., neighboring voxels are added, only when all the voxels meet the
      required conditions. In this study, two radiologists segmented lung tumors using
      a manual method and the proposed method, and the results of both methods were
      compared. The proposed method showed a high sensitivity of 81.68-84.81% and a
      high dice similarity coefficient (DSC) of 0.86-0.88 compared with the manual
      method. In addition, the SPRG intraclass correlation coefficient (ICC) was 0.998
      (CI 0.997-0.999, p < 0.01), showing that the SPRG method is highly reliable. If
      our proposed method is used for segmentation and volumetric measurement of
      lesions, then objective and accurate results and shorter data analysis time are
      possible.

PMID- 29380152
TI  - In vivo biosensors: mechanisms, development, and applications.
AB  - In vivo biosensors can recognize and respond to specific cellular stimuli. In
      recent years, biosensors have been increasingly used in metabolic engineering and
      synthetic biology, because they can be implemented in synthetic circuits to
      control the expression of reporter genes in response to specific cellular
      stimuli, such as a certain metabolite or a change in pH. There are many types of
      natural sensing devices, which can be generally divided into two main categories:
      protein-based and nucleic acid-based. Both can be obtained either by directly
      mining from natural genetic components or by engineering the existing genetic
      components for novel specificity or improved characteristics. A wide range of new
      technologies have enabled rapid engineering and discovery of new biosensors,
      which are paving the way for a new era of biotechnological progress. Here, we
      review recent advances in the design, optimization, and applications of in vivo
      biosensors in the field of metabolic engineering and synthetic biology.

PMID- 29380155
TI  - A coupled bimodal SPECT-CT imaging and brain kinetics studies of zolmitriptan
      encapsulated nanostructured polymeric carriers.
AB  - The present investigation deals with preparation and characterization of anti
      migraine zolmitriptan (ZMT) nanostructured polymeric carriers for nose to brain
      drug targeting. The drug-loaded colloidal nanocarriers of ZMT were prepared by
      modified ionic gelation of cationic chitosan with anionic sodium tripolyphosphate
      and characterized for particle size, zeta potential, and entrapment efficiency.
      Further, in order to investigate nose to brain drug targeting, biodistribution,
      and brain kinetics studies were performed using 99mtechnetium radiolabeled
      nanocarriers (99mTc-ZMTNP) in Swiss albino mice. The results were compared with
      intranasal pure drug solution (99mTc-ZMT) and intravenous nanocarriers (99mTc
      ZMTNP). A single photon emission computerized tomography (SPECT) radioimaging
      studies were also carried out to visualize and confirm brain uptake of
      nanocarriers. The optimized nanocarriers showed particle size of 161 nm,
      entrapment efficiency of 80.6%, and zeta potential of + 23.7 mV. The
      pharmacokinetic parameters, Cmax, and AUC0-infinity values for ZMT concentration
      in the brain expressed as percent radioactivity per gram of brain in intranasal
      and intravenous route of administration were calculated. The brain Cmax and AUC0
      infinity values found in three groups, intranasal 99mTc-ZMTNP, intranasal 99mTc
      ZMT, and intravenous 99mTc-ZMTNP were (0.427 and 1.889), (0.272 and 0.7157), and
      (0.204 and 0.9333), respectively. The higher Cmax values of intranasal 99mTc
      ZMTNP suggests better brain uptake as compared to other routes of administration.
      The significant higher values of nose to brain targeting parameters namely, drug
      targeting index (5.57), drug targeting efficiency (557.08%), and nose to brain
      drug direct transport (82.05%) confirmed drug targeting to brain via nasal route.
      The coupled bimodal SPECT-CT scintigrams confirm the brain uptake of intranasal
      99mTc-ZMTNP demonstrating major radioactivity accumulation in brain. This study
      conclusively demonstrated the greater uptake of ZMT-loaded nanocarriers by nose
      to brain drug targeting, which proves promising drug delivery system.

PMID- 29380156
TI  - Dairy product intake and bone properties in 70-year-old men and women.
AB  - : In the present population-based study including 70-year-old men and women,
      total dairy product intake was associated with a weak positive association with
      tibia trabecular and cortical cross-sectional areas. PURPOSE: Milk consumption
      has recently been suggested to increase fracture risk. Therefore, we aimed to
      investigate associations between dairy product consumption and peripheral bone
      properties. Furthermore, we explored whether consumption of milk and fermented
      dairy products affected bone properties differently. METHODS: The Healthy Aging
      Initiative is a population-based, cross-sectional study investigating the health
      of 70-year-old men and women. Out of the 2904 individuals who met the inclusion
      criteria, data on self-reported daily dairy product consumption (dl/day),
      peripheral quantitative computed tomography (pQCT) examinations at the 4 and 66%
      scan sites of the tibia and radius, and dual-energy X-ray absorptiometry (DXA)
      scans were collected from 2040 participants. Associations between dairy product
      consumption and bone properties were examined using multiple linear regression
      models adjusted for sex, muscle area, meal size, dietary protein proportion,
      current smoking status, and objectively measured physical activity. RESULTS:
      Total dairy product intake was associated with larger trabecular (2.296 (95% CI,
      0.552-4.039) mm2, per dl/day increase, p = 0.01) and cortical cross-sectional
      areas (CSAs) in the tibia (1.757 (95% CI, 0.683-2.830 mm2, p = 0.001) as measured
      by pQCT and higher areal bone mineral density (aBMD) of the radius (3.231 (95%
      CI, 0.764-5.698) mg/cm2, p = 0.01) as measured by DXA. No other measurement in
      the tibia, radius, femoral neck, or lower spine was associated significantly with
      dairy product intake. Bone properties did not differ according to the type of
      dairy product consumed. CONCLUSION: No evidence of a negative association between
      dairy product consumption and bone health was found. Furthermore, total dairy
      product consumption was associated with increased CSAs in the tibia, regardless
      of dairy product type. Collectively, our findings indicate the existence of a
      weak but significant positive association between dairy product consumption bone
      properties in older adults.

PMID- 29380157
TI  - Outcomes of surgery on patients with a clinically inapparent inguinal hernia as
      diagnosed by ultrasonography.
AB  - BACKGROUND: Chronic post-operative inguinal pain (CPIP) is the most significant
      complication following inguinal hernia repair. Patients without a palpable hernia
      prior to surgery seemed to report more CPIP. Our aim was to evaluate the effects
      of surgery on patients with a clinically inapparent inguinal hernia as diagnosed
      using ultrasonography. METHODS: A total of 179 hernia repairs in patients with a
      positive ultrasonography but negative physical examination were analysed
      retrospectively. Patients with recurrent hernias, femoral hernias or previous
      surgery to the inguinal canal were excluded. The primary outcome was the presence
      of chronic postoperative inguinal pain (pain > 3 months postoperatively). Data on
      preoperative complaints, surgical technique and findings during ultrasonography
      and surgery were also studied in relation to the development of CPIP. RESULTS: A
      quarter (25.1%) of the patients reported chronic postoperative pain. Female
      gender (p = 0.03), high BMI (p = 0.04) and atypical symptoms prior to surgery (p
      < 0.001) were significant univariate risk factors for developing CPIP. Logistic
      regression showed a significant association between atypical symptoms and CPIP
      [OR = 6.31, p < 0.001, 95% CI (2.32, 17.16)], which was still present after
      correction for the significant univariate variables [OR = 4.23, p = 0.02, 95% CI
      (1.26, 14.21)]. CONCLUSION: Patients with a clinically inapparent inguinal hernia
      as diagnosed using ultrasonography report a high incidence of CPIP after elective
      hernia repair. Patients with atypical groin pain prior to surgery are especially
      prone to CPIP. It is questionable whether these hernias should be classified and
      treated as symptomatic inguinal hernias. The results advocate taking other causes
      of groin pain into consideration before choosing surgical treatment.

PMID- 29380159
TI  - Experimental characterization and constitutive modeling of the biomechanical
      behavior of male human urethral tissues validated by histological observations.
AB  - This work aims at observing the mechanical behavior of the membranous and spongy
      portions of urethrae sampled on male cadavers in compliance with French
      regulations on postmortem testing, in accordance with the Scientific Council of
      body donation center of Grenoble. In this perspective, a thermostatic water tank
      was designed to conduct ex vivo planar tension tests in a physiological
      environment, i.e., in a saline solution at a temperature of [Formula: see text]
      [Formula: see text]. In order to observe the anisotropy of the tissues, the
      samples were tested in two directions. Tests consisting of a series of load
      unload cycles of increasing amplitudes were performed to highlight their viscous
      behavior. The results were then discussed according to the microstructure of
      tissue, which was investigated using different staining methods and histological
      analysis. The observed behaviors were then fitted using an anisotropic
      hyperelastic or a visco-hyperelastic matrix-fiber model.

PMID- 29380158
TI  - Incidence, etiology, management, and outcomes of flank hernia: review of
      published data.
AB  - PURPOSE: To review the published data describing the incidence, etiology,
      management, and outcomes of flank hernia. METHODS: A retrospective review of
      articles identified with an online search (using the terms "flank hernia", "flank
      bulge", "lateral hernia", "retroperitoneal aorta hernia", and "open radical
      nephrectomy") was performed. Studies exclusively on lumbar hernia or subcostal
      hernia were excluded. RESULTS: All articles retained for analysis (N = 26) were
      uncontrolled series or case reports; there were no controlled trials. The
      incidence of incisional hernia in the flank was ~ 17% (total patients analyzed =
      1,061). Flank hernia repair was accomplished successfully with a variety of
      techniques, with overall mean rates of perioperative complications, chronic post
      procedure pain, and recurrence equal to 20, 11, and 7%, respectively. Mesh
      utilization was universal. CONCLUSIONS: The available data of outcomes of flank
      hernia repair are not of high quality, and recommendations essentially consist of
      expert opinions. Operative approach (open vs. laparoscopic) and mesh insertion
      details have varied, but reasonable results appear possible with a number of
      techniques.

PMID- 29380160
TI  - PEEP titration: the effect of prone position and abdominal pressure in an ARDS
      model.
AB  - BACKGROUND: Prone position and PEEP can both improve oxygenation and other
      parameters, but their interaction has not been fully described. Limited data
      directly compare selection of mechanically "optimal" or "best" PEEP in both
      supine and prone positions, either with or without changes in chest wall
      compliance. To compare best PEEP in these varied conditions, we used an
      experimental ARDS model to compare the mechanical, gas exchange, and hemodynamic
      response to PEEP titration in supine and prone position with varied abdominal
      pressure. METHODS: Twelve adult swine underwent pulmonary saline lavage and
      injurious ventilation to simulate ARDS. We used a reversible model of intra
      abdominal hypertension to alter chest wall compliance. Response to PEEP levels of
      20,17,14,11, 8, and 5 cmH2O was evaluated under four conditions: supine, high
      abdominal pressure; prone, high abdominal pressure; supine, low abdominal
      pressure; and prone, low abdominal pressure. Using lung compliance determined
      with esophageal pressure, we recorded the "best PEEP" and its corresponding
      target value. Data were evaluated for relationships among abdominal pressure,
      PEEP, and position using three-way analysis of variance and a linear mixed model
      with Tukey adjustment. RESULTS: Prone position and PEEP independently improved
      lung compliance (P < .0001). There was no interaction. As expected, intra
      abdominal hypertension increased the PEEP needed for the best lung compliance (P
      < .0001 supine, P = .007 prone). However, best PEEP was not significantly
      different between prone (12.8 +/- 2.4 cmH2O) and supine (11.0 +/- 4.2 cmH2O)
      positions when targeting lung compliance CONCLUSIONS: Despite complementary
      mechanisms, prone position and appropriate PEEP exert their positive effects on
      lung mechanics independently of each other.

PMID- 29380161
TI  - Cerebellar involvement in patients withprimary Sjogren's syndrome: diagnosis and
      treatment.
AB  - The aim of this study is to describe the clinical features of cerebellar
      involvement in patients with primary Sjogren's syndrome (pSS). We retrospectively
      analyzed the manifestations, treatments, and outcomes in patients with pSS
      cerebellar complication in Peking Union Medical College Hospital and cases
      reported in literature. Altogether 13 patients were identified. They were 2 males
      and 11 females with a mean age at disease onset of 45.2 +/- 14.6 years. Nine
      (69.2%) patients went to the clinic because of ataxia, and pSS was not suspected
      until accidental screening for autoantibodies. Dysarthria (7, 59.8%), limb tremor
      (4, 30.8%), and nystagmus (2, 15.4%) were the rest symptoms related to
      cerebellum. Of the patients, 81.8% (9/11) had abnormal cerebrospinal fluid
      findings, and 11 patients (84.6%) had cerebellar atrophy in the brain MRI. Dry
      eyes and dry mouth were detected in 9 (69.2%) and 7 (59.8%) patients, while
      positive objective xerostomia and ocular test in 82.5% (7/8) and 100% (10/10) of
      the patients, respectively. Anti-Ro/SSA antibody was positive in 12 (92.3%) and
      anti-La/SSB in 6 (46.2%) patients. Glucocorticoids were applied in 12 patients
      (92.3%). Cyclophosphamide (3, 20.1%), mycophenolatemofetil (1, 7.7%), and
      hydroxychloroquine (4, 30.8%) were chosen as immunosuppressants or anti
      inflammatory drug. During a median follow-up of 9 months (range, 1-18 months), 8
      (61.5%) patients remained stable, 3 (20.1%) patients were in remission, and 2
      (15.4%) patients were in progression. Clinical cerebellar complication secondary
      to pSS was rare, and sometimes pSS was not suspected until accidental screening
      for autoantibodies. Because the onset of cerebellar manifestation is often
      insidious and rapid deteriorates, early diagnosis and empirical aggressive
      glucocorticoid treatment is warranted.

PMID- 29380163
TI  - Correction to: Tubulointerstitial nephritis-induced hypophosphatemic osteomalacia
      in Sjogren's syndrome: a case report and review of the literature.
AB  - The Funding statement was omitted from the original publication; the authors have
      requested that this be noted and now presented in this article.

PMID- 29380162
TI  - Therapeutic response to prednisone in relation to age in polymyalgia rheumatica:
      a comparison study.
AB  - The aim of this study was to evaluate the impact of age on the therapeutic
      response to prednisone. This was a retrospective, monocentric study. We included
      patients diagnosed with PMR, according to ACR 2012 criteria. Patients were
      classified into two groups according to age (above or below 60 years old). We
      registered demographic, clinical, biological, imaging data, and therapeutic
      response profile. Local inflammation was evaluated at baseline with PET/CT
      imaging score. The treatment was standardised. The main endpoint was a
      corticosteroid dependence defined by the recurrence of PMR symptoms and/or the
      increase of CRP at two times. We included 14 patients younger than 60 years old
      (mean age 54 +/- 0.8) and 28 patients older than 60 (mean age 75.8 +/- 1.5). The
      "young PMR" group was mainly male (60 vs 27%; p < 0.05). Both groups were similar
      regarding morning stiffness, disease duration, WBC count, and CRP. The intensity
      of FDG uptake was lower (score of 16.9 +/- 1.7 vs 26.5 +/- 3.0; p < 0.05), there
      were more dependence on corticosteroids (60 vs 20%; p < 0.05) and methotrexate
      was more necessary (35 vs 6.5%; p < 0.05) in "young PMR" group. Young patients
      diagnosed with PMR are mostly men, are more dependent on corticosteroids, and
      have a lower PET-CT score at baseline in comparison to elderly patients diagnosed
      with PMR.

PMID- 29380164
TI  - Correction to: Effect of daily low dose prednisone, divided or single daily dose,
      in the treatment of African Americans with early rheumatoid arthritis.
AB  - One of the author's name on this article was incorrectly spelled as "Shuling Li".
      The correct spelling is "Shuling Liu" and is now presented correctly in this
      article.

PMID- 29380165
TI  - Impact of cardiovascular risk factors on the achievement of therapeutic goals in
      psoriatic arthritis: is there any association?
AB  - Cardiovascular risk factors (CVRFs) have been related to poorer responses to
      systemic therapy in psoriatic arthritis (PsA). We aimed to evaluate the potential
      association between CVRFs and the achievement of therapeutic goals in PsA
      patients receiving systemic therapy. A cross-sectional study was carried out at
      25 rheumatology outpatient clinics in Spain. PsA patients with established
      disease who were treated with conventional and biologic systemic therapies were
      included. The treatment goals measured were minimal disease activity (MDA) and
      very low disease activity (VLDA) responses. The relationship between MDA/VLDA and
      CVRFs was evaluated by uni- and multivariate models. Of a total of 227 patients,
      133 (58.6%) and 26 (11.5%) patients were in MDA and VLDA, respectively. Tobacco
      use (crude OR 0.54), sedentary lifestyle (crude OR 1.95), hyperuricemia (crude OR
      2.01) and obesity (crude OR 1.54) were related to the likelihood of MDA in the
      univariate model (p < 0.25), while in multivariate analysis, a sedentary
      lifestyle (OR 3.13, 95%CI 1.50-6.53; p = 0.002) increased the odds of having
      reached MDA. Obesity (crude OR 2.2) and dyslipidaemia (crude OR 1.80) were
      associated with VLDA in univariate analysis, whereas dyslipidaemia (OR 5.3, 95%CI
      1.7-16.6; p = 0.004) increased the odds of VLDA in the multivariate model. We
      found no association between the number of CVRFs and the MDA/VLDA responses. In
      this cross-sectional, multicentre study, we could not find any relationship
      between CVRFs and lower odds of achieving stringent therapeutic goals in PsA. In
      any case, patients with psoriatic disease should be encouraged to maintain
      healthy lifestyle habits.

PMID- 29380166
TI  - Correction to: Henoch-Schonlein purpura nephritis: initial risk factors and
      outcomes in a Latin American tertiary center.
AB  - One of the author's name on this article was incorrectly spelled as "Sylvia C. L.
      Fahrat" . The correct spelling is "Sylvia C. L. Farhat" and is now presented
      correctly in this article. The original article has been corrected.

PMID- 29380167
TI  - Scores versus clinical profiles in therapeutic decisions: a positive example from
      the Italian Medicines Agency (AIFA) decisions in the field of osteoporosis.

PMID- 29380168
TI  - Rhipicephalus microplus (Acarina, Ixodidae) in Angola: evidence of its
      establishment and expansion.
AB  - Livestock constitutes a fundamental asset for the livelihood of rural communities
      in Angola. Rhipicephalus microplus (Acarina, Ixodidae) is considered to be the
      most important external parasite impacting the cattle industry in the world. The
      present work used a cross-sectional study on tick species infesting cattle in
      smallholder and commercial farms, to investigate the presence of R. microplus in
      Angola. This species was found to be recently established in certain areas of
      Cuanza-Sul and Benguela provinces. Furthermore, taking the current understanding
      of the pattern of dispersal of R. microplus into account, it is probable that
      this species is already present in other areas of the country. Animal movement
      without the necessary control measures facilitates the dispersal of this tick
      species. Consequently, R. microplus is causing rapid displacement of the native
      tick species, Rhipicephalus decoloratus. The presence of R. microplus in Angola
      constitutes a serious problem and poses a potential threat to the livestock
      sector as well as being an important risk factor for the sustainability of the
      livelihood strategies developed by smallholders.

PMID- 29380169
TI  - Ticks infesting cattle and humans in the Yungas Biogeographic Province of
      Argentina, with notes on the presence of tick-borne bacteria.
AB  - This study was performed to determine the tick species that infest cattle and
      humans throughout an altitudinal gradient in the Yungas Biogeographic Province of
      Argentina. The presence of tick-borne bacteria of the genera Rickettsia,
      Ehrlichia and Borrelia in the collected ticks was also evaluated. Samples of
      ticks parasitizing cattle and humans were carried out in different seasons.
      Questing ticks (adults and nymphs) were collected from vegetation and analyzed to
      detect the presence of Rickettsia, Ehrlichia and Borrelia by a battery of
      different PCRs. Five species of hard ticks were found parasitizing cattle:
      Amblyomma sculptum, Amblyomma tonelliae, Amblyomma hadanii, Haemaphysalis
      juxtakochi and Ixodes pararicinus. Amblyomma sculptum (immature and adults), A.
      tonelliae (immature and adults), A. hadanii (larvae) and one nymph of I.
      pararicinus were found attached to humans. Rickettsia amblyommatis was detected
      in one nymph of A. hadanii. DNA of a Borrelia genospecies belonging to the B.
      burgdorferi s.l. complex (phylogenetically related to haplotypes previously
      reported in Ixodes aragaoi from Uruguay and I. pararicinus from Argentina) was
      detected in adults of I. pararicinus. Amblyomma sculptum and I. pararicinus
      appear to be the tick species more frequent on cattle in the YBP from Argentina,
      and A. sculptum and A. tonelliae, were the main ticks found attached to humans.
      The medical importance of the bacteria of the genus Rickettsia and Borrelia
      detected in this work remains unknown.

PMID- 29380170
TI  - Description of a cryptic thermophilic (pro)phage, CBP1 from Caldibacillus debilis
      strain GB1.
AB  - This study characterizes a cryptic (pro)phage-related sequence within the
      Caldibacillus debilis GB1 genome, designated CBP1.CBP1 is a Siphoviridae-like
      genome highly related to GBVS1 from Geobacillus sp. 6k51. The CBP1genome is a
      37,315 bp region containing 69 putative ORFs with a GC content of 42% flanked on
      both sides by host DNA integrated into the main bacterial chromosome (contig 16).
      Bioinformatic analyses identified cassettes of genes within the CBP1 genome that
      were similar in function, yet distinct in sequence, from genes previously
      identified in GBVS1. All of CBP1 genes had less than 60% amino acid sequence
      identity with GBVS1by tBLASTx, with the exception of the TMP repeat gene. CBP1
      possessed all the necessary genes to undergo a temperate/lytic phage life cycle,
      including excision, replication, structural genes, DNA packaging, and cell lyses.
      Proteomic analysis of CBP1 revealed the expression of 5 proteins. One of the
      expressed proteins was a transcriptional regulator protein homologous to the
      bacteriophage lambda repressor protein (cI) expressed in high amounts from the
      CBP1 region, consistent with a lysogenic phage in a repressed state. The CBP1
      protein expression profile during host growth provides unique insight into
      thermophilic Siphoviridae-like phages in the repressed state within their host
      cells.

PMID- 29380171
TI  - Java Tea (Orthosiphon stamineus) protected against osteoarthritis by mitigating
      inflammation and cartilage degradation: a preclinical study.
AB  - The effect of Orthosiphon stamineus aqueous (OSA) extract against osteoarthritis
      (OA) was investigated in explant cartilage culture and in postmenopausal OA rat
      model. Female rats were bilaterally ovariectomized (OVX). Osteoarthritis was
      induced after surgical recovery, by intra-articular injection of monosodium
      iodoacetate (MIA) into the right knee. Rats were grouped (n = 8) into: healthy
      sham control; non-treated OA; OA + diclofenac (positive control 5 mg/kg); and two
      doses OSA (150-300 mg/kg). After 4 weeks' treatment, rats were evaluated for OA
      related parameters and biomarkers. The OSA reduced proteoglycan and ROS release
      from the cartilage explants under inflammatory (IL-1b) conditions. In the OA
      induced rats' cartilages, the OSA downregulated the mRNA expressions for IL
      1beta, IL-6, IL-10, TNF-alpha, NF-kappabeta, NOS2, PTGS2, PTGER2, ACAN, COL2A1,
      MMP1, MMP13, ADAMTS4, ADAMTS5 and TIMP1, mostly dose-dependently. The OSA reduced
      the OA rats' serum levels for PGE2, CTX-II, TNF-alpha, MMP1, MMP13, PIINP, OPG,
      RANKL, OC and BALP, but not dose-dependently. The OSA contained polyphenols and
      flavonoids (tetramethoxyflavone). The OSA alleviated articular cartilage
      degradation, inflammation, collagenase/aggrecanase activities, to improve joint
      and subchondral bone structure. O. stamineus mitigated osteoarthritis by
      downregulating inflammation, peptidases and aggrecanases, at a dose equivalent to
      about 30 mg/kg for humans.

PMID- 29380172
TI  - Continued Use of Antiplatelet Agent May Increase the Risk of Delayed Bleeding
      After Endoscopic Submucosal Dissection.

PMID- 29380173
TI  - Surgery Reduces Risk of Complications Even in High-Risk Veterans After Endoscopic
      Therapy for Biliary Stone Disease.
AB  - BACKGROUND: In otherwise healthy patients, randomized trials have shown reduced
      mortality with cholecystectomy (CCY) when compared to non-operative management
      after endoscopic retrograde cholangiopancreatography (ERCP) for biliary stone
      disease. These findings may not apply to veterans with multiple comorbidities,
      who have an increased risk of postoperative complications. AIMS: Our study
      assessed the benefit of CCY among veterans with multiple comorbidities. METHODS:
      Medical records of patients undergoing ERCP for biliary stone-related diseases
      from July 2008 to December 2016 were reviewed. Among patients who did not undergo
      CCY, risk of postoperative complications or death with CCY was estimated using
      the American College of Surgeons National Surgery Quality Improvement Program
      risk calculator. Charlson comorbidity index (CCI) and American Society of
      Anesthesiologists classification system (ASA) were used to assess patient's
      functional status. The primary outcome was incidence of recurrent biliary events
      or death with non-operative management, compared to estimated risk of serious
      postoperative complications or death with CCY. RESULTS: A total of 152 patients
      met inclusion criteria, 81 of whom did not undergo CCY. Patients managed non
      operatively were older and less medically fit than patients who underwent CCY.
      Biliary complications recurred in 23 patients managed non-operatively, including
      3 deaths due to cholangitis. Among patients with CCI >= 3 and ASA >= 3 who were
      managed non-operatively (n = 43), the risk of serious biliary events was
      significantly higher than estimated risk of serious postoperative complications
      with laparoscopic CCY (26 vs 5%, p < 0.001). CONCLUSION: Our study suggests that
      non-operative management is associated with a higher risk of complications than
      laparoscopic CCY, even among veterans with significant comorbidities.

PMID- 29380174
TI  - Residual Lesions on Capsule Endoscopy Is Associated with Postoperative Clinical
      Recurrence in Patients with Crohn's Disease.
AB  - BACKGROUND: In order to optimize postoperative therapy in patients with Crohn's
      disease (CD), it is important to detect endoscopic recurrence preceding clinical
      recurrence. However, we have little knowledge about how high the rate of residual
      lesions is and whether these lesions have an influence on postoperative course or
      not. AIMS: To assess residual lesions in small bowel immediately after surgery.
      METHODS: Capsule endoscopy (CE) was performed immediately after surgery (< 3
      months), and endoscopic activity was assessed using the Lewis score (LS) composed
      of the highest tertile score (in first, second, and third tertile) and the
      stenosis score (in whole small intestine). The relationship between these
      residual lesions and postoperative clinical recurrence was prospectively
      evaluated. RESULTS: After assessing patency using a patency capsule, CE was
      performed in 25 patients. The mean LS was 751.3, and 84.0% (21/25) had endoscopic
      activity. These lesions were detected by preoperative examinations in 0% and by a
      serosal side view during surgery in 16.0%. Regarding the cumulative clinical
      recurrence rate according to endoscopic severity (normal, mild, and moderate-to
      severe) immediately after surgery, no significant difference was found. However,
      comparing groups divided according to the highest tertile score, the cumulative
      clinical recurrence rate was significantly higher in the group with the highest
      third tertile score. Furthermore, patients with ulcers in the third tertile had a
      significantly higher recurrence rate. CONCLUSIONS: Many cases with CD had
      endoscopic activity immediately after "curative" surgery. These residual lesions,
      especially in the distal small intestine, were associated with postoperative
      clinical recurrence.

PMID- 29380176
TI  - Marital Adjustment and Its Relationship with Religious Orientations Among Iranian
      Infertile and Fertile Women: A Cross-Sectional Study.
AB  - This study aimed to determine the status of marital adjustment and its
      relationship with religious orientations in fertile and infertile women. This
      study was conducted on 160 infertile and 320 fertile Muslim Iranian women. There
      was significant difference in terms of marital adjustment in two groups. There
      was significant relationship between marital adjustments with intrinsic religious
      orientation in two groups; however, there was no significant relationship between
      marital adjustments with extrinsic religious orientation. The results suggest
      that intrinsic religious orientation is likely to increase marital adjustment in
      fertile and infertile women. However, further studies should be performed to
      assess the association of religious orientations with marital adjustment in other
      communities and religions.

PMID- 29380175
TI  - Combined and Alternating Topical Steroids and Food Elimination Diet for the
      Treatment of Eosinophilic Esophagitis.
AB  - BACKGROUND: Few studies have examined combined or alternating treatment
      algorithms in eosinophilic esophagitis. AIMS: We conducted a retrospective cohort
      study to ascertain the efficacy and adherence to a combined and alternating
      treatment approach with topical corticosteroids and 2-food elimination diet for
      pediatric EoE. METHODS: Patients were prescribed a 2-food elimination diet (milk
      and soy) and topical corticosteroid (fluticasone or oral viscous budesonide) for
      3 months, after which the steroid was discontinued and 2-food elimination diet
      continued for 3 months. An EGD was performed at baseline, 3 and 6 months.
      Clinical, endoscopic, and histologic data were extracted from electronic medical
      records. Nonparametric tests assessed adherence and outcomes. RESULTS: Twenty
      nine eosinophilic esophagitis cases were included (mean age 11.5 years, 61%
      male). Complete adherence to combined therapy and 2-food elimination diet alone
      was 75 and 79%, respectively. Median eosinophil counts decreased from 51 to 2
      eosinophils/hpf (p < 0.001) after combined treatment and rebounded to 31 (p =
      0.07) after 2FED alone. Dysphagia improved after both the combined and 2-food
      elimination diet alone treatment approaches (52 vs. 11% and 10%; p = 0.001,
      0.005). Nonsignificant improvements in endoscopic findings were documented across
      the length of follow-up. CONCLUSIONS: An initial combined treatment approach
      resulted in significant improvements in symptoms and histologic findings. While
      symptomatic improvements continued with 2-food elimination diet alone, the
      histologic improvement was not maintained. While loss to follow-up may obscure
      the efficacy of 2-food elimination diet alone, a combined/alternating treatment
      approach merits assessment in a larger prospective study.

PMID- 29380177
TI  - Prophylactic use of the implantable cardioverter-defibrillator and its effect on
      the long-term survival, cardiovascular and sudden cardiac death in nonischemic
      cardiomyopathy patients-a systematic review and meta-analysis.
AB  - Implantable cardioverter-defibrillator (ICD) has shown to reduce sudden cardiac
      death and overall mortality in patients with dilated cardiomyopathy. The recently
      published DANISH trial has shown conflicting outcomes on the long-term survival
      in patients with prophylactic implantation of ICD in Non-Ischemic Cardiomyopathy
      (NICM). Two independent reviewers searched MEDLINE, PUBMED, Ovid, CINAHL,
      clinicaltrials.gov , and Cochrane Registry for randomized control trials (RCT's)
      comparing ICD to medical treatment (MT). Six RCT's enrolling 3389 patients (ICD =
      1554 and MT = 1835) were included for final analysis. The primary outcomes were
      mortality comparing ICD to MT, 231 vs 337 (OR = 0.74, CI = 0.62-0.90, p = 0.002,
      and I2 = 0%) favoring ICD. On comparing to amiodarone only, there were 47 deaths
      in the ICD arm vs 71 deaths in amiodarone arm, (OR = 0.66, CI = 0.44-0.98, p =
      0.04, I2 0%), to placebo and usual care only (excluding amiodarone); there were
      225 deaths in ICD patients compared to 266 in the placebo and usual care arm, (OR
      = 0.73, CI = 0.59-0.92, p = 0.007, I2 = 15%). The results of our analysis from
      these six RCTs clearly support the ongoing benefit of prophylactic ICD
      implantation and support current recommendations for ICD implantation in NICM
      patients. More RCT's at a larger scale are needed to further elucidate benefits
      of both ICD and CRT-D in this post PARADIGM era where MT is at a pinnacle in
      reducing morbidity and mortality in heart failure patients.

PMID- 29380178
TI  - beta-Thalassemia intermedia: a comprehensive overview and novel approaches.
AB  - beta-Thalassemia intermedia is a clinical condition of intermediate gravity
      between beta-thalassemia minor, the asymptomatic carrier, and beta-thalassemia
      major, the transfusion-dependent severe anemia. It is characterized by a
      significant clinical polymorphism, which is attributable to its genetic
      heterogeneity. Ineffective erythropoiesis, chronic anemia, and iron overload
      contribute to the clinical complications of thalassemia intermedia through
      stepwise pathophysiological mechanisms. These complications, including
      splenomegaly, extramedullary erythropoiesis, iron accumulation, leg ulcers,
      thrombophilia, and bone abnormalities can be managed via fetal hemoglobin
      induction, occasional transfusions, chelation, and in some cases, stem cell
      transplantation. Given its clinical diversity, thalassemia intermedia patients
      require tailored approaches to therapy. Here we present an overview and novel
      approaches to the genetic basis, pathophysiological mechanisms, clinical
      complications, and optimal management of thalassemia intermedia.

PMID- 29380179
TI  - Pomalidomide with or without dexamethasone for relapsed/refractory multiple
      myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum.
AB  - Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM
      plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma
      (RRMM) were examined retrospectively in a real-world clinical practice setting in
      Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum,
      who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58
      (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and
      LEN, respectively. The median overall survival (OS) was not reached. The median
      time to treatment failure (TTF) was 4.4 months. The best response was recorded in
      96 patients, with a 31% overall response rate (ORR) and a 79% rate of achieving
      at least stable disease. Number of pre-POM regimens >= 5, non-IgG-type M-protein,
      and time from initial therapy to POM or POM/DEX therapy < 2 years were associated
      with shorter TTF and OS. Frequent (> 10%) severe adverse events included
      neutropenia (55.1%), thrombocytopenia (33.7%), anemia (30.6%), febrile
      neutropenia (12.2%), fatigue (11.2%), and anorexia (10.2%). In conclusion, POM
      and POM/DEX showed substantial efficacy against RRMM, but new combination
      therapies with POM are needed to improve efficacy further without causing
      hematologic toxicities.

PMID- 29380181
TI  - Classical Hodgkin lymphoma type post-transplant lymphoproliferative disorder in a
      kidney transplant recipient: a diagnostic pitfall.
AB  - We report a case of classical Hodgkin lymphoma type post-transplant
      lymphoproliferative disorder (HL-PTLD) after kidney transplantation to highlight
      the difficulty of distinguishing this disorder from Hodgkin lymphoma-like PTLD
      (HL-like PTLD). Through this case report and literature review, we seek to
      clarify definitive pathologic features to differentiate these two conditions. A
      38-year-old male kidney transplant recipient who had been receiving
      immunosuppressants was admitted to our hospital with unidentified high fever.
      Computed tomography images and blood tests indicated a lymphoproliferative
      disorder. Abdominal lymph node biopsy was performed, and microscopic examination
      revealed the presence of many large atypical cells in a background of dense T
      cell accumulation. The large, atypical cells were positive for Epstein-Barr Virus
      (EBV)-encoded small RNAs (EBER) in situ hybridization, EBV-LMP1, CD30 and PAX5,
      but negative for CD15, CD20 and CD45. Except for CD15-negativity, this
      immunohistochemical pattern was consistent with that of classical Hodgkin
      lymphoma. By close examination of the above immunoreactivities and the patient's
      subsequent chemosensitive clinical course, we finally made a diagnosis of HL
      PTLD.

PMID- 29380183
TI  - Intravitreal dexamethasone implant with retinal photocoagulation for adult-onset
      Coats' disease.
AB  - PURPOSE: To report a case of adult-onset Coats' disease with secondary retinal
      vasoproliferative tumor managed with dexamethasone intravitreal implant and
      retinal photocoagulation. METHODS: Case study. RESULTS: A 41-year-old female with
      counting finger vision was diagnosed with Coats' disease with secondary retinal
      vasoproliferative tumor in right eye. Fundus examination revealed exudative
      retinopathy involving posterior pole and a retinal tumor located in the
      inferotemporal quadrant. Optical coherence tomography scan confirmed massive
      exudative neurosensory detachment and fundus fluorescein angiography showed areas
      of telangiectatic vessels with capillary non-perfusion. Intravitreal injection of
      dexamethasone implant was done initially followed by laser photocoagulation when
      the detachment resolved. There was significant improvement in patient's visual
      acuity with no further recurrence of exudation. CONCLUSION: Intravitreal
      dexamethasone implant Ozurdex((r)) (Allergan, Inc., Irvine, Calif., USA) may be
      an effective initial therapeutic approach for Coats' disease with massive
      exudation.

PMID- 29380184
TI  - Ocular Demodex folliculorum: prevalence and associated symptoms in an Irish
      population.
AB  - PURPOSE: To investigate the prevalence of ocular Demodex folliculorum (DF) in an
      Irish population. To validate a modified Ocular Surface Disease Index
      questionnaire and employ it to evaluate the relationship between dry eye symptoms
      and the presence of DF. METHODS: One hundred and fifty-six subjects were enrolled
      in an epidemiological cross-sectional prevalence study. Each subject completed a
      novel questionnaire on ocular symptoms and was assessed for the presence of DF.
      Data was analysed to assess prevalence and to search for significant links
      between each symptom and DF. RESULTS: An overall prevalence of 68% was found.
      Total mean number of DF found on microscopic examination was 3.83 mites per
      subject (range 0-25). The presence of symptoms was higher among individuals with
      DF (P = 0.04). Itch was found to be the symptom most significantly associated
      with the presence and number of DF (P = 0.025 and P = 0.035, respectively). The
      questionnaire showed good internal consistency (Cronbach's alpha; alpha > 0.7)
      and good reliability (Intra-class Correlation Co-efficient; ICC > 0.7). The
      sensitivity and specificity of a positive symptom result using the questionnaire
      were 70.8% and 46.9%, respectively. CONCLUSION: There is a strong association
      between the prevalence of DF and symptoms, in particular itchy eyes. However, not
      all patients with DF will be symptomatic. The newly developed questionnaire is a
      reliable instrument for measuring change in symptoms over a period of time and
      suitable for observing patient reported outcomes in interventional treatment
      studies.

PMID- 29380180
TI  - Targeting autophagy in lymphomas: a double-edged sword?
AB  - Autophagy (also known as macroautophagy) is a lysosomal degradation pathway for
      the clearance of cellular materials, which manifests as an adaptive response to
      stress stimuli. Over the past decade, numerous studies have linked autophagy with
      cancer initiation, progression, and chemoresistance. Autophagy defects in normal
      cells facilitate tumorigenesis; paradoxically, enhanced autophagy allows
      prolonged survival in cancer cells upon nutrient shortage, low oxygen, or
      chemotherapies. However, the mechanism underlying the switch from the
      cytoprotective role of autophagy to autophagic cell death remains incompletely
      understood. Here, I review the latest advances in understanding the role of
      autophagy in lymphomas, current challenges, and future directions.

PMID- 29380182
TI  - Novel findings from the Asian Lymphoma Study Group: focus on T and NK-cell
      lymphomas.
AB  - T and NK-cell lymphomas are aggressive neoplasms with a unique epidemiological
      distribution, demonstrating higher prevalence in Asian countries compared to the
      West. Through the efforts of international collaboration, significant progress
      has been made especially on the biological understanding and clinical management
      of rare lymphoma subtypes including NK/T-cell lymphomas and monomorphic
      epitheliotropic intestinal T-cell lymphoma. In this review, we summarize the
      current status of lymphoma research conducted by the Asian Lymphoma Study Group
      and highlight key updates on the advancement of T and NK-cell lymphoma research.

PMID- 29380185
TI  - Intravitreal dexamethasone implant as an option for anti-inflammatory therapy of
      tuberculosis uveitis.
AB  - INTRODUCTION: Tuberculosis-associated uveitis remains a diagnostic and
      therapeutic challenge. After diagnosis of tuberculosis and initiation of anti
      tuberculosis therapy for tuberculosis uveitis, the clinical responses are
      favorable. However, at 4-6 weeks of the therapy, there commonly occurs
      paradoxical deterioration due to an increase in inflammation which is often
      accompanied by cystoid macular edema. Thus, adjuvant administration of anti
      inflammatory regimen should be considered. For this purpose, systemic and
      periocular steroids, systemic and intravitreal immunosuppressive agents have been
      tested. Nevertheless, there is no report in the literature about intravitreal
      dexamethasone slow-release implants for the treatment of this inflammatory
      condition. METHODS: Case presentation. RESULTS: We presented a tuberculosis
      uveitis case whose ocular inflammation is partially modified by systemic and
      periocular steroid injections and then well controlled by the intravitreal
      dexamethasone implant. CONCLUSION: Intravitreal dexamethasone implant injection
      seems to be a safe and potent option for the treatment of macular edema secondary
      to tuberculosis uveitis.

PMID- 29380186
TI  - The Effect of Some Natural Essential Oils Against Bovine Mastitis Caused by
      Prototheca zopfii Isolates In Vitro.
AB  - The aim of the study was to evaluate the effect of essential oils obtained from
      Thymus vulgaris L., Origanum vulgare L., Origanum majerana L., Mentha * piperita
      L. and Allium ursinum L. against Prototheca zopfii strains that cause
      inflammation of the udder (mastitis) in cows. The study was conducted on ten
      strains derived from milk samples. The microdilution method was used to determine
      the sensitivity of P. zopfii strains to the studied essential oils, and the disk
      diffusion method was used to determine the sensitivity to antifungal
      chemotherapeutics. The plates were incubated for 48 h at 37  degrees C under
      aerobic conditions. All strains of algae were sensitive to the essential oils
      marjoram, thyme and oregano and resistant to mint and garlic oils. MIC values
      ranged from 0.25 to 1 MUl/ml. Marjoram oil demonstrated the greatest activity,
      and oregano oil the weakest. Among the antifungal agents tested, 90% of strains
      showed sensitivity to nystatin. One of the tested strains (71/IV) was resistant
      to all investigated antifungal agents. The tested essential oils are known to
      have anti-algae activity and can be used as natural agents for prophylaxis in
      animals, particularly in mastitis-affected cows.

PMID- 29380187
TI  - Correction to: Resistance Mechanism in a Terbinafine-Resistant Strain of
      Microsporum canis.
AB  - In the initial online publication, the name of author Hock Siew Han was given
      incorrectly as Han Hock Siew. The original article has been corrected.

PMID- 29380188
TI  - Comparative Study of the Effects of Fluconazole and Voriconazole on Candida
      glabrata, Candida parapsilosis and Candida rugosa Biofilms.
AB  - Infections by non-albicans Candida species are a life-threatening condition, and
      formation of biofilms can lead to treatment failure in a clinical setting. This
      study was aimed to demonstrate the in vitro antibiofilm activity of fluconazole
      (FLU) and voriconazole (VOR) against C. glabrata, C. parapsilosis and C. rugosa
      with diverse antifungal susceptibilities to FLU and VOR. The antibiofilm
      activities of FLU and VOR in the form of suspension as well as pre-coatings were
      assessed by XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5
      carboxanilide] reduction assay. Morphological and intracellular changes exerted
      by the antifungal drugs on Candida cells were examined by scanning electron
      microscope (SEM) and transmission electron microscope (TEM). The results of the
      antibiofilm activities showed that FLU drug suspension was capable of killing C.
      parapsilosis and C. rugosa at minimum inhibitory concentrations (MICs) of 4* MIC
      FLU and 256* MIC FLU, respectively. While VOR MICs ranging from 2* to 32* were
      capable of killing the biofilms of all Candida spp tested. The antibiofilm
      activities of pre-coated FLU were able to kill the biofilms at 1/4* MIC FLU and
      1/2* MIC FLU for C. parapsilosis and C. rugosa strains, respectively. While pre
      coated VOR was able to kill the biofilms, all three Candida sp at 1/2* MIC VOR.
      SEM and TEM examinations showed that FLU and VOR treatments exerted significant
      impact on Candida cell with various degrees of morphological changes. In
      conclusion, a fourfold reduction in MIC50 of FLU and VOR towards ATCC strains of
      C. glabrata, C. rugosa and C. rugosa clinical strain was observed in this study.

PMID- 29380189
TI  - Respiratory changes in subclavian vein diameters predicts fluid responsiveness in
      intensive care patients: a pilot study.
AB  - The present pilot study investigated whether respiratory variation in subclavian
      vein (SCV) diameters correlates with fluid responsiveness in mechanically
      ventilated patients. Monocentric, prospective clinical study on fluid
      responsiveness in adult sedated, mechanically ventilated ICU patient, monitored
      with the PiCCOTM system (Pulsion Medical System, Germany), and requiring a fluid
      challenge (FC). A 10-min fluid bolus of 500 mL of 0.9% saline was administered.
      Cardiac output (CO) and dynamic parameters [stroke volume variation (SVV) and
      pulse pressure variation (PPV)] measured by transpulmonary thermodilution and
      pulse contour analysis (PiCCOTM) as well as classical hemodynamic parameters were
      recorded at baseline and after FC. Fluid responsiveness was described as an
      increase in CO of >= 15%. Ultrasound measurements obtained in the subclavian long
      axis view were used to calculate the SCVvariability index. A cut-off value for
      SCV variation for the prediction of fluid responsiveness was determined using
      receiver operating curve (ROC) analysis. Nine of 20 FCs (45%) induced an increase
      in CO of >= 15%. At baseline, the SCVvariability index was greater in responders
      than in non-responders (34.0 +/- 21.4 vs. 9.0 +/- 5.5; p = 0.0005). Diagnostic
      performance for the SCVvariability index revealed a cut-off value of 14 with a
      sensitivity of 100% [Confidence interval (CI) 95% (90; 100)] and a specificity of
      82% [CI 95% (48; 98)] for the prediction of fluid responsiveness. Other
      parameters, such as SVV and PPV, could not predict fluid responsiveness. The
      correlation coefficient between CO variation and the SCVvariability index was
      0.73 (p < 0.001). The SCVvariability index was a reliable, non-invasive parameter
      for the prediction of fluid responsiveness at the bedside of mechanically
      ventilated, critically ill patients in this pilot study.

PMID- 29380190
TI  - Comparison of cardiac output optimization with an automated closed-loop goal
      directed fluid therapy versus non standardized manual fluid administration during
      elective abdominal surgery: first prospective randomized controlled trial.
AB  - An intraoperative automated closed-loop system for goal-directed fluid therapy
      has been successfully tested in silico, in vivo and in a clinical case-control
      matching. This trial compared intraoperative cardiac output (CO) in patients
      managed with this closed-loop system versus usual practice in an academic medical
      center. The closed-loop system was connected to a CO monitoring system and
      delivered automated colloid fluid boluses. Moderate to high-risk abdominal
      surgical patients were randomized either to the closed-loop or the manual group.
      Intraoperative final CO was the primary endpoint. Secondary endpoints were
      intraoperative overall mean cardiac index (CI), increase from initial to final
      CI, intraoperative fluid volume and postoperative outcomes. From January 2014 to
      November 2015, 46 patients were randomized. There was a lower initial CI (2.06
      vs. 2.51 l min-1 m-2, p = 0.042) in the closed-loop compared to the control
      group. No difference in final CO and in overall mean intraoperative CI was
      observed between groups. A significant relative increase from initial to final CI
      values was observed in the closed-loop but not the control group (+ 28.6%, p =
      0.006 vs. + 1.2%, p = 0.843). No difference was found for intraoperative fluid
      management and postoperative outcomes between groups. There was no significant
      impact on the primary study endpoint, but this was found in a context of
      unexpected lower initial CI in the closed-loop group.Trial registry number ID
      RCB/EudraCT: 2013-A00770-45. ClinicalTrials.gov Identifier NCT01950845, date of
      registration: 17 September 2013.

PMID- 29380192
TI  - Interleukin-13 stimulates production of nitric oxide in cultured human nasal
      epithelium.
AB  - The diversity and extent of signaling functions of nitric oxide (NO) in cell
      physiology as well as its presence and influence as a common component of ambient
      air pollution and tobacco smoke are gaining increasing research attention
      relative to both health and disease. While cellular NO production is typically
      associated with inflammatory cells and processes, the airway epithelium
      particularly of the paranasal sinuses, has been documented to be a rich source of
      excreted NO. Inasmuch as excreted NO derives from both mucosal and inflammatory
      cell sources, distinguishing the individual contribution of these compartments to
      total excreted cellular NO is potentially problematic. We simulated an
      inflammatory mucosal environment by stimulating human nasal epithelial cultures
      with interleukin-13 (IL-13), a mediator produced by eosinophils in asthma,
      allergic rhinitis, and sinusitis. While a consistent baseline of NO excretion in
      control cultures was documented, widely variable individual responses to IL-13
      exposure were observed in companion cultures maintained under identical
      conditions and tested at the same time. These studies suggest that cellular NO
      excretion by the healthy epithelial mucosa is subject to considerable individual
      variability and may be significantly elevated among some individuals in the
      presence of IL-13 stimulation.

PMID- 29380191
TI  - Reporting of health-related quality of life in randomized controlled trials
      involving palliative systemic therapy for esophagogastric cancer: a systematic
      review.
AB  - BACKGROUND: Health-related quality of life (HRQoL) assessments are increasingly
      incorporated into oncological randomized controlled trials (RCTs). The quality of
      HRQoL reporting in RCTs concerning palliative systemic treatment for advanced
      esophagogastric cancer is currently unknown. Therefore, we conducted a systematic
      review to investigate the quality of HRQoL reporting over time. METHODS: PubMed,
      CENTRAL and EMBASE were searched for RCTs concerning systemic treatment for
      advanced esophagogastric cancer up to February 2017. The Minimum Standard
      Checklist for Evaluating HRQoL Outcomes in Cancer Clinical Trials was used to
      rate the quality of HRQoL reporting. Univariate and multivariate generalized
      linear regression analysis was used to investigate factors affecting the quality
      of reporting over time. RESULTS: In total, 37 original RCTs (N = 10,887 patients)
      were included. The quality of reporting was classified as 'very limited' in 4
      studies (11%), 'limited' in 24 studies (65%), and 'probably robust' in 9 studies
      (24%). HRQoL reporting did not improve over time, and it did not improve
      following the publication of the CONSORT-PRO statement in 2013. The publication
      of HRQoL findings in a separate article and second-line treatment were associated
      with better reporting. CONCLUSIONS: HRQoL reporting in RCTs concerning palliative
      systemic therapy for advanced esophagogastric cancer is limited and has not
      improved over time. This systematic review provides specific recommendations for
      authors to improve HRQoL reporting: formulate hypotheses a priori, clearly
      describe instrument administration, and handle missing data and interpret
      findings appropriately.

PMID- 29380194
TI  - Protective Effect of Morphine Against the Oxidant-Induced Injury in H9c2 Cells.
AB  - There are some indications that morphine may exert myocardial protective effects
      under certain conditions. The aim of the present study was to investigate the
      effect of morphine on viability and oxidative state of H9c2 cells (rat
      cardiomyoblasts) influenced by oxidative stress that was elicited by exposure to
      tert-butyl hydroperoxide (t-BHP). Our experiments showed that pretreatment with
      morphine before the addition of t-BHP markedly improved cell viability. Morphine
      was able to increase total antioxidant capacity of H9c2 cells and to reduce the
      production of reactive oxygen species, protein carbonylation, and lipid
      peroxidation. Cellular damage caused by t-BHP was associated with low levels of
      p38 MAPK and GSK-3beta phosphorylation. Pretreatment with morphine augmented p38
      phosphorylation, and the increased phospho-p38/p38 ratio was preserved even in
      the presence of t-BHP. Morphine did not change the level of GSK-3beta
      phosphorylation, but interestingly, the phospho-GSK-3beta/GSK-3beta ratio
      significantly increased after subsequent incubation with t-BHP. Furthermore,
      morphine exposure resulted in upregulation of the antioxidant enzyme catalase.
      The protective effect of morphine was abrogated by the addition of the PI3K
      inhibitor wortmannin and/or p38 MAPK inhibitor SB203580. It can be concluded that
      morphine may protect H9c2 cells against oxidative stress and that this protection
      is at least partially mediated through activation of the p38 MAPK and PI3K/GSK
      3beta pathways.

PMID- 29380193
TI  - The emu oil emulsified in egg lecithin and butylated hydroxytoluene enhanced the
      proliferation, stemness gene expression, and in vitro wound healing of adipose
      derived stem cells.
AB  - In recent decades, mesenchymal stem cells originated from adipose tissue (adipose
      derived stem cells, ASCs) have gained increased attention for production of cell
      based therapeutics. Emu oil as a natural compound showed antioxidant effects in
      previous studies. The goal of this study was to investigate the effect of crude
      emu oil on the proliferation, cell cycle progression, stemness genes expression,
      and in vitro wound healing potential of ASCs. An emulsion of emu oil was prepared
      using egg lecithin and butylated hydroxytoluene to improve bioavailability and
      solubility of emu oil in the expansion medium. The ASCs were treated using a
      series of emu oil concentrations in emulsion form, diluted in expansion medium
      (0.03-3 mg/ml). The emu oil-free emulsion was used as control treatment. The
      results revealed that emu oil (1.25 mg/ml) in emulsion form significantly (p <
      0.001) increased ASCs proliferation and colony formation. Additionally, emu oil
      caused upregulation of stemness marker genes (Sox2, Oct4, Nanog, and Nestin) (p <
      0.05). The cell cycle analysis after emu oil treatments showed an increase in the
      population of ASCs in S-phase of the cell cycle. Besides, an accelerated in vitro
      scratch wound healing was observed in emu oil-treated ASCs. Emu oil enhanced
      proliferation, colony formation, stemness genes expression, and in vitro wound
      healing of ASCs. These findings suggest that emu oil treatment could maintain the
      stemness of ex vivo cultivated ASCs and enhance their regenerative potential.

PMID- 29380195
TI  - Assisted Dying in Australia and Limiting Court Involvement in Withdrawal of
      Nutrition and Hydration.

PMID- 29380197
TI  - Sonochemical degradation of triclosan in water in a multifrequency reactor.
AB  - Degradation of triclosan (TCS) by multifrequency ultrasound (US) was studied at
      high and low frequencies. Frequency effect on initial degradation rates was
      analyzed, and an optimum frequency was found. Power density always has a positive
      effect on degradation rates over the whole equipment work range. A reaction
      mechanism similar to that proposed by Serpone resulted in a pseudo-linear model
      that fitted statistically better than the nonlinear model proposed by Okitsu.
      Pulsed US showed a positive effect on degradation rates; however, simultaneous
      analysis of the effect of power, frequency, pulse time, and silent time did not
      show a clear trend for degradation as a function of pulse US variables. According
      to these results and those for degradation in the presence of radical scavengers,
      it was concluded that US TCS degradation was taking place in the bubble/liquid
      interface. A toxicity test was conducted by Microtox(r), showing a decrease in
      toxicity as TCS concentration decreased and increase in toxicity after total
      depletion of TCS. Eight possible degradation by-products were identified by GC-MS
      analysis, and a degradation pathway was proposed.

PMID- 29380196
TI  - Association of detoxification enzymes with butene-fipronil in larvae and adults
      of Drosophila melanogaster.
AB  - Insecticide resistance is a major challenge in successful insect pest control as
      the insects have the ability to develop resistance to various widely used
      insecticides. Butene-fipronil is a novel compound with high toxicity to insects
      and less toxicity to the non-target organisms. In the present study, the effect
      of butene-fipronil alone and in combination with three enzyme inhibitors,
      piperonyl butoxide (PBO), diethyl maleate (DEM), and triphenyl phosphate (TPP),
      was carried out on larvae and adults of Drosophilia melanogaster. Our results
      indicated that the co-toxicity indices of butene-fipronil + PBO, butene-fipronil
      + TPP, and butene-fipronil + DEM mixtures were 437.3, 335.0, and 210.3,
      respectively, in the second-instar larvae, while 186.6, 256.2, and 238.5,
      respectively, in the adults, indicating synergistic effects. Interestingly,
      butene-fipronil increased the expression of CYP28A5 in the larvae; CYP9F2,
      CYP304A1, CYP28A5, and CYP318A1 in the female adults; and CYP303A1 and CYP28A5 in
      the male adults. Furthermore, high-level expression of Est-7 was observed in the
      female adults compared to larvae and male adults. Our results suggest that there
      is no difference in butene-fipronil metabolism in larvae and male and female
      adults of D. melanogaster.

PMID- 29380198
TI  - Identifying external nutrient reduction requirements and potential in the
      hypereutrophic Lake Taihu Basin, China.
AB  - Reducing external nutrient loads is the first step for controlling
      eutrophication. Here, we identified external nutrient reduction requirements and
      potential of strategies for achieving reductions to remediate a eutrophic water
      body, Lake Taihu, China. A mass balance approach based on the entire lake was
      used to identify nutrient reduction requirements; an empirical export coefficient
      approach was introduced to estimate the nutrient reduction potential of the
      overall program on integrated regulation of Taihu Lake Basin (hereafter referred
      to as the "Guideline"). Reduction requirements included external total nitrogen
      (TN) and total phosphorus (TP) loads, which should be reduced by 41-55 and 25
      50%, respectively, to prevent nutrient accumulation in Lake Taihu and to meet the
      planned water quality targets. In 2010, which is the most seriously polluted
      calendar year during the 2008-2014 period, the nutrient reduction requirements
      were estimated to be 36,819 tons of N and 2442 tons of P, and the potential
      nutrient reduction strategies would reduce approximately 25,821 tons of N and
      3024 tons of P. Since there is a net N remaining in the reduction requirements,
      it should be the focus and deserves more attention in identifying external
      nutrient reduction strategies. Moreover, abatement measures outlined in the
      Guideline with high P reduction potential required large monetary investments.
      Achieving TP reduction requirement using the cost-effective strategy costs about
      80.24 million USD. The design of nutrient reduction strategies should be enacted
      according to regional and sectoral differences and the cost-effectiveness of
      abatement measures.

PMID- 29380199
TI  - Acute sensitivity of the killifish Nothobranchius furzeri to a combination of
      temperature and reference toxicants (cadmium, chlorpyrifos and 3,4
      dichloroaniline).
AB  - Aquatic organisms of inland waters are often subjected to a combination of
      stressors. Yet, few experiments assess mixed stress effects beyond a select group
      of standard model organisms. We studied the joint toxicity of reference toxicants
      and increased temperature on the turquoise killifish, Nothobranchius furzeri, a
      promising model for ecotoxicological research due to the species' short life
      cycle and the production of drought-resistant eggs. The acute sensitivity of the
      larval stage (2dph) to three compounds (cadmium, 3,4-dichloroaniline and
      chlorpyrifos) was tested in combination with a temperature increase of 4  degrees
      C, mimicking global warming. Dose-response relationships were used to calculate
      96h-LC50 of 0.28 mg/L (24  degrees C) and 0.39 mg/L (28  degrees C) for cadmium,
      96h-LC50 of 9.75 mg/L (24  degrees C) and 6.61 mg/L (28  degrees C) for 3,4
      dichloroaniline and 96h-LC50 of 15.4 MUg/L (24  degrees C) and 14.2 MUg/L (28 
      degrees C) for chlorpyrifos. After 24 h of exposure, the toxicity of all tested
      compounds was exacerbated under increased temperature. Furthermore, the
      interaction effect of cadmium and temperature could be predicted by the stress
      addition model (SAM). This suggests the applicability of the model for fish and
      at the same time indicates that the model could be suitable to predict effects of
      temperature-toxicant interactions.

PMID- 29380200
TI  - Characterization and cancer risk assessment of VOCs in home and school
      environments in gran La Plata, Argentina.
AB  - Three areas are highlighted in Gran La Plata, Argentina: industrial, urban, and
      residential. In this work, the levels of volatile organic compounds (VOCs) in
      indoor air of homes and schools in those areas were analyzed, through the use of
      passive monitors. The study period is between 2007 and 2010. Higher levels of
      VOCs were found in homes and schools in the industrial zone, higher than the
      levels corresponding to urban and residential. Taking into account the
      relationship between indoor and outdoor levels of VOCs, they have ratios (I/O)
      between 1.5 and 10 are evidenced contributions of emission sources of VOCs both
      indoor and outdoor. Complementarily, we estimated the life time cancer risk (LCR)
      for benzene, styrene, trichloroethylene, and tetrachloroethylene in children who
      spend their time mostly in such indoor environments. The results show high LCR
      values for benzene, which exceed acceptable values for the US EPA.

PMID- 29380202
TI  - A study through batch tests on the analytical determination and the fate and
      removal of methamphetamine in the biological treatment of domestic wastewater.
AB  - Methamphetamine (MET) is one of the most used illicit drugs in Europe and is
      recognized as one of the Emerging Organic Micropollutants. It is discharged into
      the sewerage system from different sources and then enters the wastewater
      treatment plants. The present study aimed at providing a better knowledge of the
      fate of MET through the wastewater treatment plants. The study addressed two
      different issues: (1) optimization of the analytical methods for MET
      determination in both liquid and sludge phases, focusing on the effects of
      potentially interfering substances and (2) investigation on the behaviour of MET
      in the biological treatment process, with specific concern for the biomass
      activity at different drug concentrations. Results of the study on issue 1
      highlighted that the applied analytical method for MET determination (UPLC-MS/MS)
      is affected by the main components of wastewater for about 9-23%, which is
      comparable with the uncertainties of the method (about +/- 28%). The method
      showed also to be repeatable and reliable (recovery > 75%; repeatability < 10
      15%; bias uncertainty < 30%), and relatively easy-to-use. Therefore, it can be
      considered suitable for measurements on routine base in the WWTPs. Batch tests
      conducted to address issue 2 showed total removal of 84, 90, and 96% at 50, 100,
      and 200 ng/L initial MET concentration, respectively, for a contact time of 6 h.
      The removal process was mainly ascribed to the biological activity of both
      heterotrophic and autotrophic bacteria. The pseudo first-order kinetic model
      provided the best fitting of the experimental data of the overall biological
      processes at all the tested concentrations. Furthermore, the respirometric tests
      showed that MET does not induce any inhibition. Adsorption of MET on activated
      sludge was always very low.

PMID- 29380201
TI  - Effects of air pollution on hospital visits for pneumonia in children: a two-year
      analysis from China.
AB  - Although the effect of air pollution on respiratory health has been identified,
      few studies can be available to evaluate the association of air pollution with
      hospital visits for children's pneumonia in China. To explore whether high
      concentrations of air pollutants (including PM2.5, PM10, NO2, and SO2) are
      related to hospital visits for pneumonia in children, we conducted a population
      based time-series study in Ningbo, China, from January 1st, 2014 to November 1st,
      2015. We used a generalized additive Poisson regression model to calculate risk
      ratios and 95% confidence intervals for the associations of air pollutants and
      hospital visits for pneumonia in children and found that these four pollutants
      were associated with the increased hospital visits for pneumonia in children
      (1.3% for PM2.5, 1.0% for PM10, 2.9% for NO2, 5.0% for SO2 per 10-MUg/m3 increase
      in PM2.5, PM10, NO2, and SO2, respectively). Stronger associations were observed
      in the cold seasons and among children under 5 years.

PMID- 29380204
TI  - CME instructions: Regadenoson use in chronic kidney disease and end-stage renal
      disease: A focused review.

PMID- 29380203
TI  - Cd and Cu accumulation, translocation and tolerance in Populus alba clone
      (Villafranca) in autotrophic in vitro screening.
AB  - The present study investigated accumulation, translocation and tolerance of
      autotrophic Populus alba clone "Villafranca" in response to excess concentrations
      of cadmium (Cd) and copper (Cu) provided to the plants. For this purpose,
      increasing concentrations of Cd (0, 5, 50 and 250 MUM) and Cu (0, 5, 50, 250 and
      500 MUM) were administered to the growth medium in which micropropagated poplar
      plantlets were exposed to metal treatments for 15 days. Filter bags, instead of
      the conventional in vitro screening, were applied to improve the experimental
      design. Results showed that Cd and Cu increased in shoots and roots at increasing
      metal concentration in the medium. The highest Cd content was found in leaves,
      while the highest Cu content was found in roots. In "Villafranca", Cu showed
      toxic effects on the development of the seedlings, especially at the highest
      concentrations, reducing plant dry mass. However, the tolerance index (Ti)
      indicated good tolerance in this clone under exposure to excess metal
      concentrations, whereas plants had higher translocation factor (Tf). We recommend
      in vitro selection of tolerant genotypes, aimed at providing early indication on
      accumulation potentiality and tolerance capability in research on plant
      sensitivity to excess heavy metal concentrations.

PMID- 29380206
TI  - Study on the Structural Effect of Maltoligosaccharides on Cytochrome c Complexes
      Stabilities by Native Mass Spectrometry.
AB  - Noncovalent interactions between ligands and targeting proteins are essential for
      understanding molecular mechanisms of proteins. In this work, we investigated the
      interaction of Cytochrome c (Cyt c) with maltoligosaccharides, namely maltose
      (Mal II), maltotriose (Mal III), maltotetraose (Mal IV), maltopentaose (Mal V),
      maltohexaose (Mal VI) and maltoheptaose (Mal VII). Using electrospray ionization
      mass spetrometry (ESI-MS) assay, the 1:1 and 1:2 complexes formed by Cyt c with
      maltoligosaccharide ligand were observed. The corresponding association constants
      were calculated according to the deconvoluted spectra. The order of the relative
      binding affinities of the selected oligosaccharides with Cyt c were as Mal III >
      Mal IV > Mal II > Mal V > Mal VI > Mal VII. The results indicated that the
      stability of noncovalent protein complexes was intimately correlated to the
      molecular structure of bound ligand. The relevant functional groups that could
      form H-bonds, electrostatic or hydrophobic forces with protein's amino residues
      played an important role for the stability of protein complexes. In addition, the
      steric structure of ligand was also critical for an appropriate interaction with
      the binding pocket of proteins.

PMID- 29380205
TI  - RNA binding protein 24 regulates the translation and replication of hepatitis C
      virus.
AB  - The secondary structures of hepatitis C virus (HCV) RNA and the cellular proteins
      that bind to them are important for modulating both translation and RNA
      replication. However, the sets of RNA-binding proteins involved in the regulation
      of HCV translation, replication and encapsidation remain unknown. Here, we
      identified RNA binding motif protein 24 (RBM24) as a host factor participated in
      HCV translation and replication. Knockdown of RBM24 reduced HCV propagation in
      Huh7.5.1 cells. An enhanced translation and delayed RNA synthesis during the
      early phase of infection was observed in RBM24 silencing cells. However, both
      overexpression of RBM24 and recombinant human RBM24 protein suppressed HCV IRES
      mediated translation. Further analysis revealed that the assembly of the 80S
      ribosome on the HCV IRES was interrupted by RBM24 protein through binding to the
      5'-UTR. RBM24 could also interact with HCV Core and enhance the interaction of
      Core and 5'-UTR, which suppresses the expression of HCV. Moreover, RBM24 enhanced
      the interaction between the 5'- and 3'-UTRs in the HCV genome, which probably
      explained its requirement in HCV genome replication. Therefore, RBM24 is a novel
      host factor involved in HCV replication and may function at the switch from
      translation to replication.

PMID- 29380207
TI  - The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple
      negative subtype and early recurrence.
AB  - PURPOSE: The platelet-derived growth factor (PDGF) signalling pathway is often
      dysregulated in cancer and PDGF-receptor expression has been linked to
      unfavourable prognostic factors in breast cancer (e.g. ER negativity, high Ki67
      and high grade). This study aimed to evaluate the expression of PDGFRalpha,
      PDGFRbeta and ligand PDGF-CC in breast cancer in relation to molecular subtypes
      and prognosis. METHODS: Protein expression of tumour and/or stromal cell
      PDGFRalpha, PDGFRbeta and PDGF-CC was evaluated in primary tumours (N = 489),
      synchronous lymph node metastases (N = 135) and asynchronous recurrences (N = 39)
      using immunohistochemistry in a prospectively maintained cohort of primary breast
      cancer patients included during 1999-2003. Distant recurrence-free interval
      (DRFi) was the primary end-point. RESULTS: High expression of all investigated
      PDGF family members correlated to increasing Nottingham histopathological grade
      and high Ki67. Tumour cells displayed high expression of PDGFRalpha in 20%, and
      PDGF-CC in 21% of primary tumours, which correlated with the triple-negative
      subtype (TNBC). Patients with high PDGF-CC had inferior prognosis (P = 0.04) in
      terms of 5-year DRFi, whereas PDGFRalpha was up-regulated in lymph node
      metastasis and recurrences compared to primary tumours. High primary tumour
      PDGFRalpha was associated with increased risk of central nervous system (CNS)
      recurrence. CONCLUSIONS: High PDGFRalpha and PDGF-CC expression were linked to
      breast cancer with an aggressive biological phenotype, e.g. the TNBC subtype, and
      high PDGF-CC increased the risk of 5-year distant recurrence. Tumour cell
      PDGFRalpha was significantly up-regulated in lymph node metastases and
      asynchronous recurrences. Our findings support an active role of the PDGF
      signalling pathway in tumour progression.

PMID- 29380208
TI  - Machine learning to parse breast pathology reports in Chinese.
AB  - INTRODUCTION: Large structured databases of pathology findings are valuable in
      deriving new clinical insights. However, they are labor intensive to create and
      generally require manual annotation. There has been some work in the
      bioinformatics community to support automating this work via machine learning in
      English. Our contribution is to provide an automated approach to construct such
      structured databases in Chinese, and to set the stage for extraction from other
      languages. METHODS: We collected 2104 de-identified Chinese benign and malignant
      breast pathology reports from Hunan Cancer Hospital. Physicians with native
      Chinese proficiency reviewed the reports and annotated a variety of binary and
      numerical pathologic entities. After excluding 78 cases with a bilateral lesion
      in the same report, 1216 cases were used as a training set for the algorithm,
      which was then refined by 405 development cases. The Natural language processing
      algorithm was tested by using the remaining 405 cases to evaluate the machine
      learning outcome. The model was used to extract 13 binary entities and 8
      numerical entities. RESULTS: When compared to physicians with native Chinese
      proficiency, the model showed a per-entity accuracy from 91 to 100% for all
      common diagnoses on the test set. The overall accuracy of binary entities was 98%
      and of numerical entities was 95%. In a per-report evaluation for binary entities
      with more than 100 training cases, 85% of all the testing reports were completely
      correct and 11% had an error in 1 out of 22 entities. CONCLUSION: We have
      demonstrated that Chinese breast pathology reports can be automatically parsed
      into structured data using standard machine learning approaches. The results of
      our study demonstrate that techniques effective in parsing English reports can be
      scaled to other languages.

PMID- 29380209
TI  - Lymph drainage of the upper limb and mammary region to the axilla: anatomical
      study in stillborns.
AB  - PURPOSE: We studied the lymphatic drainage of the upper limb and mammary region
      directing to the axilla to investigate whether independent pathways can be
      observed or whether anastomoses and shared drainage occur between them. This
      analysis aimed to assess the safety of axillary reverse mapping (ARM) in breast
      cancer treatment and to understand the development of lymphedema after sentinel
      lymph node biopsy (SLNB) alone. METHODS: Seven unfixed stillborn fetuses were
      injected with a modified Gerota mass in the peri-areolar area, palm and dorsum of
      the hands, formalin fixed, and then submerged in 10% hydrogen peroxide solution.
      Microsurgical dissection was then performed on the subcutaneous cellular tissue
      of the upper limb, axillary region, and anterior thorax to expose the lymphatic
      vessels and lymph nodes. RESULTS: The dye injected into the upper limb reached
      either the lateral axillary group, known to be exclusively responsible for upper
      limb drainage, or the anterior group, which is typically related to breast
      drainage. There was great proximity among the pathways and lymph nodes.
      Communicating lymphatic vessels among these groups of lymph nodes were also found
      in all studied cases. DISCUSSION: Lymphedema remains a challenging morbidity in
      breast cancer treatment. ARM and SLNB aim to avoid unnecessary damage to the
      lymphatic drainage of the upper limb. However, our anatomical study suggests that
      ARM may have potential oncological risks because preserved lymph nodes may harbor
      malignant cells due their proximity, overlapping drainage pathways, and
      connecting lymph vessels among lymph nodes.

PMID- 29380210
TI  - A positive move: proton therapy in Australia.

PMID- 29380211
TI  - Perceptions of Zika Virus Prevention Among College Students in Florida.
AB  - Zika virus in Florida prompted a strong public health response, due to its causal
      association with birth defects. While primarily spread by mosquitos, Zika can be
      transmitted sexually. The spread of Zika may influence reproductive behaviors
      among sexually active persons in Florida. This study examined factors associated
      with willingness to change birth control method use in response to Zika virus
      among college women and men in Florida. Women and men ages 18-44 at a Florida
      university (N = 328) were surveyed about Zika knowledge, beliefs about Zika, use
      of contraceptives and condoms, and socio-demographics between November 2016-April
      2017. The outcome variable was willingness to change birth control method were
      Zika in their area. Logistic regression models in SAS 9.4 were used. Most
      participants were women (80%), and 47% were 20-22 years old. Only 27% of
      participants said they would change their birth control method if Zika were in
      their area. Participants who knew that Zika was sexually transmitted were more
      likely to be willing to change their birth control method (aOR = 1.71, 95%CI 1.01
      2.91). Participants who agreed or strongly agreed that they were fearful of being
      infected with Zika virus were more likely to be willing to change their birth
      control methods (aOR = 1.98, 95%CI 1.07-3.67). This study found that, among
      Florida college students, Zika beliefs and knowledge were associated with a
      willingness to change birth control method in response to Zika. Understanding the
      factors that motivate individuals to change reproductive behaviors during an
      emerging health issue can help tailor preventative messages.

PMID- 29380212
TI  - Decline in Prescription Opioids Attributable to Decreases in Long-Term Use: A
      Retrospective Study in the Veterans Health Administration 2010-2016.
AB  - BACKGROUND: Improved understanding of temporal trends in short- and long-term
      opioid prescribing may inform efforts to curb the opioid epidemic. OBJECTIVE: To
      characterize the prevalence of short- and long-term opioid prescribing in the
      Veterans Health Administration (VHA) from 2010 to 2016. DESIGN: Observational
      cohort study using VHA databases. PARTICIPANTS: All patients receiving at least
      one outpatient prescription through the VHA during calendar years 2010 through
      2016. MAIN MEASURES: Prevalence of opioid use from 2010 through 2016, stratified
      by short-term, intermediate-term, and long-term use. Temporal trends in
      discontinuation among existing long-term users and initiation of new long-term
      use and the net impact on rates of long-term opioid use. Relative likelihood of
      transitioning to long-term opioid use contrasted with use patterns in the prior
      year. KEY RESULTS: The prevalence of opioid prescribing was 20.8% in 2010, peaked
      at 21.2% in 2012, and declined annually to 16.1% in 2016. Between 2010 and 2016,
      reductions in long-term opioid prescribing accounted for 83% of the overall
      decline in opioid prescription fills. Comparing data from 2010-2011 to data from
      2015-2016, declining rates in new long-term use accounted for more than 90% of
      the decreasing prevalence of long-term opioid use in the VHA, whereas increases
      in cessation among existing long-term users accounted for less than 10%. The
      relative risk of transitioning to long-term use during 2016 was 6.5 (95% CI: 6.4,
      6.7) among short-term users and 35.5 (95% CI: 34.8, 36.3) among intermediate
      users, relative to patients with no opioid prescriptions filled during 2015.
      CONCLUSIONS: Opioid prescribing trends followed similar trajectories in VHA and
      non-VHA settings, peaking around 2012 and subsequently declining. However,
      changes in long-term opioid prescribing accounted for most of the decline in the
      VHA. Recent VA opioid initiatives may be preventing patients from initiating long
      term use. This may offer valuable lessons generalizable to other healthcare
      systems.

PMID- 29380213
TI  - Medical Students' Exposure to the Humanities Correlates with Positive Personal
      Qualities and Reduced Burnout: A Multi-Institutional U.S. Survey.
AB  - BACKGROUND: Literature, music, theater, and visual arts play an uncertain and
      limited role in medical education. One of the arguments often advanced in favor
      of teaching the humanities refers to their capacity to foster traits that not
      only improve practice, but might also reduce physician burnout-an increasing
      scourge in today's medicine. Yet, research remains limited. OBJECTIVE: To test
      the hypothesis that medical students with higher exposure to the humanities would
      report higher levels of positive physician qualities (e.g., wisdom, empathy, self
      efficacy, emotional appraisal, spatial skills), while reporting lower levels of
      negative qualities that are detrimental to physician well-being (e.g.,
      intolerance of ambiguity, physical fatigue, emotional exhaustion, and cognitive
      weariness). DESIGN: An online survey. PARTICIPANTS: All students enrolled at five
      U.S. medical schools during the 2014-2015 academic year were invited by email to
      take part in our online survey. MAIN MEASURES: Students reported their exposure
      to the humanities (e.g., music, literature, theater, visual arts) and completed
      rating scales measuring selected personal qualities. KEY RESULTS: In all,
      739/3107 medical students completed the survey (23.8%). Regression analyses
      revealed that exposure to the humanities was significantly correlated with
      positive personal qualities, including empathy (p < 0.001), tolerance for
      ambiguity (p < 0.001), wisdom (p < 0.001), emotional appraisal (p = 0.01), self
      efficacy (p = 0.02), and spatial skills (p = 0.02), while it was significantly
      and inversely correlated with some components of burnout (p = 0.01). Thus, all
      hypotheses were statistically significant, with effect sizes ranging from 0.2 to
      0.59. CONCLUSIONS: This study confirms the association between exposure to the
      humanities and both a higher level of students' positive qualities and a lower
      level of adverse traits. These findings may carry implications for medical school
      recruitment and curriculum design. "[Science and humanities are] twin berries on
      one stem, grievous damage has been done to both in regarding [them]... in any
      other light than complemental." (William Osler, Br Med J. 1919;2:1-7).

PMID- 29380214
TI  - Rideshare-Based Medical Transportation for Medicaid Patients and Primary Care
      Show Rates: A Difference-in-Difference Analysis of a Pilot Program.
AB  - BACKGROUND: Transportation to primary care is a well-documented barrier for
      patients with Medicaid, despite access to non-emergency medical transportation
      (NEMT) benefits. Rideshare services, which offer greater convenience and lower
      cost, have been proposed as an NEMT alternative. OBJECTIVE: To evaluate the
      impact of rideshare-based medical transportation on the proportion of Medicaid
      patients attending scheduled primary care appointments. DESIGN: In one of two
      similar practices, all eligible Medicaid patients were offered rideshare-based
      transportation ("rideshare practice"). A difference-in-difference analytical
      approach using logistic regression with robust standard errors was employed to
      compare show rate changes between the rideshare practice and the practice where
      rideshare was not offered ("control practice"). PARTICIPANTS: Our study
      population included residents of West Philadelphia who were insured by Medicaid
      and were established patients at two academic general internal medicine practices
      located in the same building. INTERVENTION: We designed a rideshare-based
      transportation pilot intervention. Patients were offered the service during their
      reminder call 2 days before the appointment, and rides were prescheduled by
      research staff. Patients then called research staff to schedule their return trip
      home. MAIN MEASURES: We assessed the effect of offering rideshare-based
      transportation on appointment show rates by comparing the change in the average
      show rate for the rideshare practice, from the baseline period to the
      intervention period, with the change at the control practice. KEY RESULTS: At the
      control practice, the show rate declined from 60% (146/245) to 51% (34/67). At
      the rideshare practice, the show rate improved from 54% (72/134) to 68% (41/60).
      In the adjusted model, controlling for patient demographics and provider type,
      the odds of showing up for an appointment before and after the intervention
      increased 2.57 (1.10-6.00) times more in the rideshare practice than in the
      control practice. CONCLUSIONS: Results of this pilot program suggest that
      offering a rideshare-based transportation service can increase show rates to
      primary care for Medicaid patients.

PMID- 29380215
TI  - Capsule Commentary on Rivera-Caravaca et al., Soluble Fibrin Monomer Complex and
      Prediction of Cardiovascular Events in Atrial Fibrillation: The Observational
      Murcia Atrial Fibrillation Project.

PMID- 29380216
TI  - Prediction Model for Two-Year Risk of Opioid Overdose Among Patients Prescribed
      Chronic Opioid Therapy.
AB  - BACKGROUND: Naloxone is a life-saving opioid antagonist. Chronic pain guidelines
      recommend that physicians co-prescribe naloxone to patients at high risk for
      opioid overdose. However, clinical tools to efficiently identify patients who
      could benefit from naloxone are lacking. OBJECTIVE: To develop and validate an
      overdose predictive model which could be used in primary care settings to assess
      the need for naloxone. DESIGN: Retrospective cohort. SETTING: Derivation site was
      an integrated health system in Colorado; validation site was a safety-net health
      system in Colorado. PARTICIPANTS: We developed a predictive model in a cohort of
      42,828 patients taking chronic opioid therapy and externally validated the model
      in 10,708 patients. MAIN MEASURES: Potential predictors and outcomes (nonfatal
      pharmaceutical and heroin overdoses) were extracted from electronic health
      records. Fatal overdose outcomes were identified from state vital records. To
      match the approximate shelf-life of naloxone, we used Cox proportional hazards
      regression to model the 2-year risk of overdose. Calibration and discrimination
      were assessed. KEY RESULTS: A five-variable predictive model showed good
      calibration and discrimination (bootstrap-corrected c-statistic = 0.73, 95%
      confidence interval [CI] 0.69-0.78) in the derivation site, with sensitivity of
      66.1% and specificity of 66.6%. In the validation site, the model showed good
      discrimination (c-statistic = 0.75, 95% CI 0.70-0.80) and less than ideal
      calibration, with sensitivity and specificity of 82.2% and 49.5%, respectively.
      CONCLUSIONS: Among patients on chronic opioid therapy, the predictive model
      identified 66-82% of all subsequent opioid overdoses. This model is an efficient
      screening tool to identify patients who could benefit from naloxone to prevent
      overdose deaths. Population differences across the two sites limited calibration
      in the validation site.

PMID- 29380217
TI  - Physician Perception of Pay Fairness and its Association with Work Satisfaction,
      Intent to Leave Practice, and Personal Health.
AB  - BACKGROUND: Primary care physicians generally earn less than specialists. Studies
      of other occupations have identified perception of pay fairness as a predictor of
      work- and life-related outcomes. We evaluated whether physicians' pay fairness
      perceptions were associated with their work satisfaction, turnover intention, and
      personal health. METHODS: Three thousand five hundred eighty-nine physicians were
      surveyed. Agreement with "my total compensation is fair" was used to assess pay
      fairness perceptions. Total compensation was self-reported, and we used validated
      measures of work satisfaction, likelihood of leaving current practice, and health
      status. Hierarchical logistic regressions were used to assess the associations
      between pay fairness perceptions and work/life-related outcomes. RESULTS: A total
      of 2263 physicians completed surveys. Fifty-seven percent believed their
      compensation was fair; there was no difference between physicians in internal
      medicine and non-primary care specialties (P = 0.58). Eighty-three percent were
      satisfied at work, 70% reported low likelihood of leaving their practice, and 77%
      rated their health as very good or excellent. Higher compensation levels were
      associated with greater work satisfaction and lower turnover intention, but most
      associations became statistically non-significant after adjusting for pay
      fairness perceptions. Perceived pay fairness was associated with greater work
      satisfaction (OR, 4.90; 95% CI, 3.94-6.08; P < 0.001), lower turnover intention
      (OR, 2.46; 95% CI, 2.01-3.01; P < 0.001), and better health (OR, 1.33; 95% CI,
      1.08-1.65; P < 0.01). DISCUSSION: Physicians who thought their pay was fair
      reported greater work satisfaction, lower likelihood of leaving their practice,
      and better overall health. Addressing pay fairness perceptions may be important
      for sustaining a satisfied and healthy physician workforce, which is necessary to
      deliver high-quality care.

PMID- 29380218
TI  - Tracking Progress in Improving Diagnosis: A Framework for Defining Undesirable
      Diagnostic Events.
AB  - Diagnostic error is a prevalent, harmful, and costly phenomenon. Multiple
      national health care and governmental organizations have recently identified the
      need to improve diagnostic safety as a high priority. A major barrier, however,
      is the lack of standardized, reliable methods for measuring diagnostic safety.
      Given the absence of reliable and valid measures for diagnostic errors, we need
      methods to help establish some type of baseline diagnostic performance across
      health systems, as well as to enable researchers and health systems to determine
      the impact of interventions for improving the diagnostic process. Multiple
      approaches have been suggested but none widely adopted. We propose a new
      framework for identifying "undesirable diagnostic events" (UDEs) that health
      systems, professional organizations, and researchers could further define and
      develop to enable standardized measurement and reporting related to diagnostic
      safety. We propose an outline for UDEs that identifies both conditions prone to
      diagnostic error and the contexts of care in which these errors are likely to
      occur. Refinement and adoption of this framework across health systems can
      facilitate standardized measurement and reporting of diagnostic safety.

PMID- 29380219
TI  - Lime-Induced Phytophotodermatitis.

PMID- 29380220
TI  - Are Mothers' Working Hours Associated with General and Abdominal Obesity in
      Children and Adolescents? The Korean National Health and Nutrition Examination
      Survey (2008-2012).
AB  - Objectives Despite an increase in the female work force and recent increase in
      childhood obesity, the association between working hours of mothers and childhood
      obesity as well as how such association differs according to mothers' weight and
      intake frequency of energy-dense, nutrition-poor (EDNP) foods remain unclear.
      Methods Data from the Korean National Health and Nutrition Examination Survey
      (2008-2012) that included samples from 3914 children in 2526 households were
      analyzed. Two-level (household-children) mixed-effects modeling was performed to
      investigate the association between mothers' working hours and childhood obesity
      based on body mass index (BMI) and waist circumference (WC). Results Long working
      hours (h) of mothers were associated with both BMI (beta = - 0.14; P = 0.324 for
      1-20 h, beta = 0.10; P = 0.334 for <= 21-40 h; beta = 0.09; P = 0.429 for 41-68
      h, beta = 0.51; P = 0.015 for >= 69 h) and WC of the child (beta = 0.06; P =
      0.809 for 1-20 h; beta = 0.46; P = 0.017 for <= 21-40 h; beta = 0.59; P = 0.004
      for 41-68 h, beta = 1.35; P < 0.001 for >= 69 h), and the mean increase was
      greater for mothers working >= 69 h compared to those working 0 h. We also
      observed that the association between mothers' working hours and child's BMI and
      WC was greater for children whose mothers were either overweight or obese and
      frequently consumed energy-dense, nutrient-poor foods (EDNP). Conclusions for
      Practice Long working hours of mothers are associated with higher BMI and WC in
      children. Thus, it is important to improve labor welfare for mothers who work
      long hours, and provide interventions to promote good health behaviors in both
      children and working mothers.

PMID- 29380221
TI  - Chordoid meningioma: a clinico-pathological study of an uncommon variant of
      meningioma.
AB  - Chordoid meningioma is a rare variant of meningioma, with a higher incidence in
      the young and a supposed association with Castleman's syndrome. They have an
      aggressive clinical course, and are assigned as WHO grade II meningiomas. To the
      best of our knowledge, 284 chordoid meningiomas have been reported in the
      literature. This series reporting 33 cases is the third largest series in
      published literature from a single Institution. We reviewed Clinico-pathological
      characteristics of 33 patients diagnosed with chordoid meningioma between 2001
      and 2015 in our institution. Forty-one specimens were available for review of
      histopathological and immunohistochemical characteristics. There were 15 men and
      18 women with mean age of 36.8 years (median 36 years, range 9-62 years) at
      diagnosis with three cases occurring in pediatric age group. The majority were
      supratentorial in location with 11 convexity, 1 falcine, 5 parasagittal, 1
      intraventricular, skull base involvement in 12 with 4 being petroclival location
      and 3 had spinal lesions. Lymphoplasmacytic infiltrates were seen in 23 cases
      with majority being T cells. MIB index varied from 1 to 14%. Five patients
      received radiotherapy for residual lesion. Two patients died (recurrence-1, post
      operative complication-1). Three patients were lost to follow up after surgery.
      The mean post-operative follow up period for the remaining was 55.3 months. Seven
      patients had recurrence of which three had it twice. This study adds to the pool
      of available data for better understanding of this variant of meningioma. These
      meningiomas occur in middle age; spinal lesions and pediatric cases are not
      uncommon. We did not find any association between surgery, post-operative
      radiotherapy and histopathological features with recurrence and survival. Small
      number of cases may be responsible for this statistical insignificance.

PMID- 29380222
TI  - Cross-Cultural Medical Care Training and Education: a National Survey of
      Pediatric Hematology/Oncology Fellows-in-Training and Fellowship Program
      Directors.
AB  - Pediatric hematologists/oncologists face complex situations such as breaking bad
      news, treatment/clinical trials discussions, and end-of-life/hospice care. With
      increasing diversity in patient and physician populations, cultural competency
      and sensitivity training covering different aspects of pediatric
      hematology/oncology (PDHO) care can help improve health care delivery and reduce
      disparities. Though it is considered a required component of fellowship training,
      there is no clearly defined curriculum meant specifically for PDHO fellows-in
      training (PDHO-F). A national online survey of 356 PDHO-F and 67 PDHO program
      directors (PDHO-PD) was conducted to assess the educational experience,
      perceptions about identifying barriers including one's own biases and trainee
      comfort in delivering culturally sensitive care in various PDHO relevant clinical
      situations. One hundred and eleven (31.2%) PDHO-F and 27 (40.3%) PDHO-PD
      responded. 30.6% of PDHO-F "strongly agreed/agreed" they received comprehensive
      cross-cultural communication (CCC) training. The top two teaching methods were
      faculty role modeling and informal teaching. Majority of CCC training is in
      medical school or residency and only 10.8% of PDHO-F reported that most of their
      CCC training was in fellowship. In most clinical situations, there was a modest
      direct correlation between the fellow's level of agreement that they received
      comprehensive CCC training and their comfort level. Comfort level with some
      clinical situations was also significantly different based on year of training.
      Fellowship training programs should have CCC curricula which use experiential
      learning models and lay the foundation for promoting cultural awareness, self
      reflection, and better patient-physician partnerships which can eventually adapt
      to and surmount the challenges unique to the physician's chosen field of
      practice.

PMID- 29380223
TI  - Thirty Years of the Journal of Cancer Education: a Review.
AB  - Since its foundation in 1986, the Journal of Cancer Education (JCE) has served as
      an important outlet for myriad aspects of cancer education and currently serves
      as the official journal of the American and European Associations for Cancer
      Education. During its history, the JCE has been under the auspices of five
      publishers, with its first full year under the current publisher, Springer, in
      2010. Print and distribution metrics from 2010 to present were obtained from
      Springer. These were compared to historical data including the first 10 years of
      the JCE, published by Dr. Bakemeier in 1995. Since its beginning, the JCE has
      consisted of four issues per year. The original contract for 256 pages per year
      has increased to an average of 858 pages from 2010 to 2014. In 2015, the JCE
      received a total of 344 submissions, up from 339 in 2014, and 262 the year
      before. This is a stark contrast to the roughly 44 submission received in 1994.
      Over this same period, the overall rejection rate has increased from 30% in 2010
      to 45% in 2015. The number of online deals has increased from 347 in 2014 to 361
      in 2015 and has been accompanied by a steady increase in the number of full-text
      article downloads: 19,000 in 2010 to 58,923 in 2015. Accordingly, the JCE has
      seen a pronounced and steady increase in impact factor, rising from 0.52 in 2009
      to 1.368 in 2015. Since moving to Springer, the JCE has seen unprecedented
      growth, receiving increasing submissions yearly, an increasing number of
      subscription deals and online full-text downloads, and a corresponding increase
      in impact factor.

PMID- 29380224
TI  - Prosthetic valve endocarditis caused by Propionibacterium species: a national
      registry-based study of 51 Swedish cases.
AB  - Propionibacterium spp. are a rare cause of infective endocarditis (IE). The
      diagnosis is difficult because the bacteria are slow-growing and growth in blood
      cultures is often misinterpreted as contamination from the skin flora. The aim of
      this study was to describe all cases of Propionibacterium spp. endocarditis in
      the Swedish national registry of IE. The registry was searched for all cases of
      IE from 1995 to 2016 caused by Propionibacterium spp. Data concerning clinical
      characteristics, treatment, and outcome were registered. A total of 51 episodes
      of definitive prosthetic valve endocarditis (PVE) caused by Propionibacterium
      spp. were identified, comprising 8% of cases of PVE during the study period.
      Almost all cases (n = 50) were male. The median time from surgery to diagnosis of
      IE was 3 years. Most patients were treated mainly with beta-lactams, partly in
      combination with aminoglycosides. Benzyl-penicillin was the most frequently used
      beta-lactam. A total of 32 patients (63%) underwent surgery. Overall, 47 patients
      (92.1%) were cured, 3 (5.9%) suffered relapse, and 1 (2.0%) died during
      treatment. IE caused by Propionibacterium spp. almost exclusively affects men
      with a prosthetic valve and findings of Propionibacterium spp. in blood cultures
      in such patients favors suspicion of a possible diagnosis of IE. In patients with
      prosthetic valves, prolonged incubation of blood cultures up to 14 days is
      recommended. The prognosis was favorable, although a majority of patients
      required cardiac surgery during treatment. Benzyl-penicillin should be the first
      line antibiotic treatment option for IE caused by Propionibacterium spp.

PMID- 29380225
TI  - Considerable variation of trough beta-lactam concentrations in older adults
      hospitalized with infection-a prospective observational study.
AB  - In older adults, few studies confirm that adequate concentrations of antibiotics
      are achieved using current dosage regimens of intravenous beta-lactam
      antibiotics. Our objective was to investigate trough concentrations of
      cefotaxime, meropenem, and piperacillin in older adults hospitalized with
      infection. We included 102 patients above 70 years of age. Total trough
      antibiotic concentrations were measured and related to suggested target
      intervals. Information on antibiotic dose, patient characteristics, and 28-day
      outcomes were collected from medical records and regression models were fitted.
      Trough concentrations for all three antibiotics exhibited considerable variation.
      Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were
      6.5 mg/L (range 0-44), 3.4 mg/L (range 0-11), and 30.2 mg/L (range 1.2-131),
      respectively. When a target range of non-species-related breakpoint - 5* non
      species-related breakpoint was applied, only 36% of patients had both values
      within the target range. Regression models revealed that severe sepsis was
      associated with varying concentration levels and increasing age and diminishing
      kidney function with high concentration levels. The study was not powered to
      demonstrate consequences in clinical outcomes. Conclusively, in older adults
      treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic
      concentrations varied considerably. Better predictors to guide dosing regimens of
      beta-lactam antibiotics or increased use of therapeutic drug monitoring are
      potential ways to address such variations.

PMID- 29380226
TI  - Infections in liver and lung transplant recipients: a national prospective
      cohort.
AB  - Infections are a major complication of solid organ transplants (SOTs). This study
      aimed to describe recipients' characteristics, and the frequency and etiology of
      infections and transplant outcome in liver and lung SOTs, and to investigate
      exposures associated to infection and death in liver transplant recipients. The
      study population included recipients of SOTs performed in Italy during a 1-year
      period in ten Italian lung transplant units and eight liver transplant units.
      Data on comorbidities, infections, retransplantation, and death were
      prospectively collected using a web-based system, with a 6-month follow-up. The
      cumulative incidence of infection was 31.7% and 47.8% in liver and lung
      transplants, respectively, with most infections occurring within the first month
      after transplantation. Gram-negatives, which were primarily multidrug-resistant,
      were the most frequent cause of infection. Death rates were 0.42 per 1000
      recipient-days in liver transplants and 1.41 per 1000 recipient-days in lung
      transplants. Infection after SOT in adult liver recipients is associated to an
      increased risk of death (OR = 13.25; p-value < 0.001). Given the frequency of
      infection caused by multidrug-resistant microorganisms in SOT recipients in Italy
      and the heavy impact of infections on the transplant outcome, the reinforcement
      of surveillance and control activities to prevent the transmission of multidrug
      resistant microorganisms in SOT recipients represents a priority. The
      implementation of the study protocol in liver and lung transplant units and the
      sharing of results have increased the awareness about the threat due to
      antimicrobial resistance in the country.

PMID- 29380227
TI  - Adherence Measurements in HIV: New Advancements in Pharmacologic Methods and Real
      Time Monitoring.
AB  - PURPOSE OF REVIEW: In this review, we present new developments in antiretroviral
      adherence, focusing on pharmacological measures and real-time adherence
      monitoring. In addition, new strategies on how to incorporate these new measures
      into research and clinical care are proposed. RECENT FINDINGS: Antiretroviral
      drug concentrations in hair and dried blood spots are two novel pharmacological
      measures of cumulative drug adherence and exposure that have been recently
      evaluated in HIV treatment and pre-exposure prophylaxis. Real-time adherence
      monitoring using electronic devices has also proven highly informative, feasible,
      and well accepted, offering the possibility for an immediate intervention when
      non-adherence is detected. Both approaches offer considerable advantages over
      traditional adherence measures in predicting efficacy. New methods to objectively
      monitor adherence in real-time and over long time periods have been developed.
      Further research is required to better understand how these measures can optimize
      adherence and, ultimately, improve clinical outcomes in HIV treatment and
      prevention.

PMID- 29380228
TI  - Do patients have a say? A narrative review of the development of patient-reported
      outcome measures used in elective procedures for coronary revascularisation.
AB  - PURPOSE: Patient-reported outcome measures (PROMs) capture health information
      from the patient's perspective that can be used when weighing up benefits, risks
      and costs of treatment. This is important for elective procedures such as those
      for coronary revascularisation. Patients should be involved in the development of
      PROMs to accurately capture outcomes that are important for the patient. The aims
      of this review are to identify if patients were involved in the development of
      cardiovascular-specific PROMs used for assessing outcomes from elective coronary
      revascularisation, and to explore what methods were used to capture patient
      perspectives. METHODS: PROMs for evaluating outcomes from elective coronary
      revascularisation were identified from a previous review and an updated
      systematic search. The studies describing the development of the PROMs were
      reviewed for information on patient input in their conceptual and/or item
      development. RESULTS: 24 PROMs were identified from a previous review and three
      additional PROMs were identified from the updated search. Full texts were
      obtained for 26 of the 27 PROMs. The 26 studies (11 multidimensional, 15
      unidimensional) were reviewed. Only nine studies reported developing PROMs using
      patient input. For eight PROMs, the inclusion of patient input could not be
      judged due to insufficient information in the full text. CONCLUSIONS: Only nine
      of the 26 reviewed PROMs used in elective coronary revascularisation reported
      involving patients in their conceptual and/or item development, while patient
      input was unclear for eight PROMs. These findings suggest that the patient's
      perspective is often overlooked or poorly described in the development of PROMs.

PMID- 29380229
TI  - How well do discrete choice experiments predict health choices? A systematic
      review and meta-analysis of external validity.
AB  - Discrete choice experiments (DCEs) are economic tools that elicit the stated
      preferences of respondents. Because of their increasing importance in informing
      the design of health products and services, it is critical to understand the
      extent to which DCEs give reliable predictions outside of the experimental
      context. We systematically reviewed the literature of published DCE studies
      comparing predictions to choices made in reality; we extracted individual-level
      data to estimate a bivariate mixed-effects model of pooled sensitivity and
      specificity. Eight studies met the inclusion criteria, and six of these gave
      sufficient data for inclusion in a meta-analysis. Pooled sensitivity and
      specificity estimates were 88% (95% CI 81, 92%) and 34% (95% CI 23, 46%),
      respectively, and the area under the SROC curve (AUC) was 0.60 (95% CI 0.55,
      0.64). Results indicate that DCEs can produce reasonable predictions of health
      related behaviors. There is a great need for future research on the external
      validity of DCEs, particularly empirical studies assessing predicted and revealed
      preferences of a representative sample of participants.

PMID- 29380230
TI  - Thyroid Hormone Promotes beta-Catenin Activation and Cell Proliferation in
      Colorectal Cancer.
AB  - Thyroid hormone status has long been implicated in cancer development. Here we
      investigated the role of thyroxine (T4) in colorectal cancer cell lines HCT 116
      (APC wild type) and HT-29 (APC mutant), as well as the primary cultures of cancer
      cells derived from patients. Cell proliferation was evaluated with standard assay
      and proliferation marker expression. beta-Catenin activation was examined
      according to nuclear beta-catenin accumulation and beta-catenin target gene
      expression. The results showed that T4 increased colorectal cancer cell
      proliferation while cell number and viability were elevated by T4 in both
      established cell lines and primary cells. Moreover, the transcriptions of
      proliferative genes PCNA, CCND1, and c-Myc were enhanced by T4 in the primary
      cells. T4 induced nuclear beta-catenin accumulation, as well as high cyclin D1
      and c-Myc levels compared to the untreated cells. In addition, the beta-catenin
      directed transactivation of CCND1 and c-Myc promoters was also upregulated by T4.
      CTNNB1 transcription was raised by T4 in HCT 116, but not in HT-29, while the
      boosted beta-catenin levels were observed in both. Lastly, the T4-mediated gene
      expression could be averted by the knockdown of beta-catenin. These results
      suggested that T4 promotes beta-catenin activation and cell proliferation in
      colorectal cancer, indicating that an applicable therapeutic strategy should be
      considered.

PMID- 29380231
TI  - Riedel's thyroiditis: clinical presentation, treatment and outcomes.
AB  - BACKGROUND: Riedel's thyroiditis (RT) is a rare inflammatory disease of the
      thyroid gland, causing compression and fibrosis of adjacent tissues. Typically
      the goiter is hard and firm. Hoarseness, dyspnea, and dysphagia may be present.
      METHODS: We retrospectively reviewed all patients known by us with RT in addition
      to all patients with appropriate ICD-10 codes evaluated at the Karolinska
      University Hospital 2003-2015. Clinical, biochemical, and histological data of
      patients with RT were recorded in detail. Histological preparations were re
      examined when available. RESULTS: RT was diagnosed in six patients. Five were
      females and the median age at first presentation was 50 years (25-81 years).
      Median follow-up time was 3.75 years (1-22 years). At diagnosis five had
      hypothyroidism. Four had extrathyroidal manifestations, and one of these had also
      distant fibrosis. One patient had a clear IgG4/IgG ratio over 40%. One patient
      was treated with tracheostomy, one with isthmectomy and one with total
      thyroidectomy. Four had been treated with glucocorticoids, four with tamoxifen,
      and two with both drugs. One had also been treated with mycophenolate mofetil
      combined with Rituximab. At the end of follow-up four was doing fine, one had
      recurrent episodes of inflammation and one had died of possible complications to
      RT. CONCLUSION: It is important to recognize RT and give adequate treatment.
      Steroids are still the mainstay of therapy but other medications against
      fibrosclerosis can be considered. Wakefulness of other fibrosing manifestations
      is essential. Immunohistochemistry can show whether IgG-4 plasma cells are
      increased which could lead to fibrosis in other organs.

PMID- 29380232
TI  - The influence of prehypertension, hypertension, and glycated hemoglobin on the
      development of type 2 diabetes mellitus in prediabetes: the Korean Genome and
      Epidemiology Study (KoGES).
AB  - BACKGROUND: It has been reported that elevated blood pressure (BP) was
      significantly associated with the increased risk for type 2 diabetes mellitus
      (T2DM). However, there is still limited information about the influence of BP on
      the risk for T2DM across the level of glycated hemoglobin (HbA1c). METHOD: In a
      cohort of the Korean Genome and Epidemiology Study (KoGES), 2830 non-diabetic
      Korean adults with prediabetes defined by HbA1c level of 5.7-6.4% were followed
      up for 10 years. Multivariate cox proportional hazards assumption was used to
      assess the risk for T2DM according to the baseline BP categories (normal,
      prehypertension and hypertension) and HbA1c level (low: 5.7-5.9% and high: 6.0
      6.4%). RESULTS: The risk for T2DM significantly increased proportionally to BP
      categories (adjusted HR; reference in normal BP, 1.32 [1.10-1.59] in
      prehypertension and 1.61 [1.35-1.92] in hypertension). Subgroup analysis
      indicated that individuals with high HbA1c had the higher risk for T2DM than
      individuals with low HbA1c regardless of BP. Additionally, combined presence of
      hypertension and high HbA1c had the highest risk for T2DM (adjusted HR: 3.82
      [3.00-4.87]). In each systolic and diastolic BP level, the risk for T2DM
      significantly increased from systolic BP >= 130 mmHg (adjusted HRs: 1.39 ([1.15
      1.71]) and diastolic BP >= 80 mmHg (adjusted HRs: 1.30 ([1.07-1.58]). CONCLUSION:
      BP and HbA1c may be useful tools in identifying individuals with prediabetes more
      potentially predisposed to T2DM. Prospective studies should be considered to
      examine whether controlling BP actually lowers the risk for T2DM.

PMID- 29380233
TI  - p38 differentially regulates ERK, p21, and mitogenic signalling in two pancreatic
      carcinoma cell lines.
AB  - Whereas the p38 MAP kinase has largely been associated with anti-proliferative
      functions, several observations have indicated that it may also have positive
      effects on proliferation. In hepatocytes, we have found that p38 has opposing
      effects on DNA synthesis when activated by EGF and HGF. Here we have studied the
      function of p38 in EGF- and HGF-induced DNA synthesis in the two pancreatic
      carcinoma cell lines AsPC-1 and Panc-1. In Panc-1 cells, the MEK inhibitor
      PD98059 reduced EGF- and HGF-induced DNA synthesis, while the p38 inhibitor
      SB203580 strongly increased the basal DNA synthesis and reduced expression of the
      cyclin-dependent kinase inhibitor (CDKI) p21. In contrast, in AsPC-1 cells, EGF-
      and HGF-induced DNA synthesis was not significantly reduced by PD98059 but was
      inhibited by SB203580. Treatment with SB203580 amplified the sustained ERK
      phosphorylation induced by these growth factors and caused a marked upregulation
      of the expression of p21, which could be blocked by PD98059. These results
      suggest that while DNA synthesis in Panc-1 cells is enhanced by ERK and strongly
      suppressed by p38, in AsPC-1 cells, p38 exerts a pro-mitogenic effect through
      MEK/ERK-dependent downregulation of p21. Thus, p38 may have suppressive or
      stimulatory effects on proliferation depending on the cell type, due to
      differential cross-talk between the p38 and MEK/ERK pathways.

PMID- 29380234
TI  - Exploring the current and future role of the pharmacists in osteoporosis
      screening and management in Malaysia.
AB  - Background Several studies have found that pharmacists can assist in screening
      and prevention of osteoporosis by referring patients for bone mineral density
      scans and counselling on lifestyle changes. In Malaysia, screening osteoporosis
      in all elderly women is not mandatory due to its cost. One approach to address
      this gap is to develop a pharmacist-led osteoporosis screening and prevention
      program. However, there is a paucity of data on the perspectives of Malaysian
      pharmacists in this area. Objective To explore the perspective of stakeholders
      (policy makers, doctors, pharmacists, nurses and patients) towards the role of
      pharmacists in osteoporosis screening and management. Setting A primary care
      clinic located within a teaching hospital in Kuala Lumpur, Malaysia. Method
      Patients (n = 20), nurses (n = 10), pharmacists (n = 11), doctors (n = 10) and
      policy makers (n = 5) were individually interviewed using a semi-structured topic
      guide. Purposive sampling was used. Interviews were transcribed verbatim and
      analysed using thematic analysis. Main outcome measure Perspective of
      stakeholders on the current and future role of pharmacists. Results All
      participants perceived pharmacists to be suppliers of medication, although there
      was some recognition of roles in providing medication advice. Nonetheless, these
      stakeholders were eager for pharmacists to expand their non-dispensing roles
      towards counselling, creating awareness and screening of osteoporosis.
      Interviewed pharmacists referred to their current role as 'robotic dispensers'
      and unanimously agreed to spread out to osteoporosis management role. Conclusion
      Under stakeholders there is a willingness to expand the role of pharmacists in
      Malaysia to non-dispensing roles, particularly in osteoporosis screening and
      management.

PMID- 29380235
TI  - Unintended consequences for patients of future personalized pharmacoprinting.
AB  - Manufacturing pharmaceuticals by the use of 3D printing is a promising way to
      achieve more personalized drug treatment. To effectively use this technology,
      patients need to continuously measure their health, and new decisions have to be
      taken, for example, regarding the number of daily drugs including how many active
      pharmaceutical substances these should contain along with decisions around size,
      shape and color. Positive as well as negative effects of pharmacoprinted medicine
      on patients are likely to occur. Negative consequences with influence on patient
      autonomy and role might include: patients not being capable or interested in
      conducting self-monitoring, loosing overview of the medical treatment, reducing
      the ability to perform self-regulation, loosing trust in the pharmacoprinted
      medicine, and not being interested in taking on a new role in medical decision
      making. These issues are discussed in the paper in order to prevent upcoming
      challenges in the area of pharmacoprinting.

PMID- 29380236
TI  - Drug related problems identified by clinical pharmacist at the Internal Medicine
      Ward in Turkey.
AB  - Background Drug-related problems (DRPs) interfere with patient optimal
      therapeutic outcomes and may be associated with higher morbidity, mortality and
      healthcare expenditures. Objective This study aimed to identify DRPs and their
      causes in a Turkish hospital. Setting Bakirkoy Dr. Sadi Konuk Teaching and
      Research Hospital, Internal Medicine Ward, Istanbul, Turkey. Method Cross
      sectional study included a total of 100 patients. Patient demographics,
      medications, and history were evaluated. Data regarding recent medications were
      analyzed by two clinical pharmacists and an Internal Medicine physician. The DRPs
      were identified via V7.0 PCNE classification. Lexicomp(r) was used to assess the
      drug-drug interactions. UpToDate(r) recommendations and national guidelines were
      applied in the assessment of compliance with approved medication procedures. Main
      outcome measures Number and causes of the potential DRPs. Results At least one
      potential DRP was seen in 80% of the patients and 163 potential DRPs were
      identified (average = 1.6 DRPs/patient). The most common causes of DRPs were
      errors in drug selection (44.78%), dose selection (27.61%) and medication
      procedures (21.47%). There were significant correlations (p < 0.05) between DRPs
      and age (r = 0.4), number of drugs used (r = 0.32), duration of hospitalization
      (r = 0.25), renal impairment (r = - 0.34) and inflammation (r = 0.31). Conclusion
      The majority of the patients had DRPs. Patients with renal impairment,
      inflammation, polypharmacy or an extended hospital stay had a much higher chance
      of developing DRPs.

PMID- 29380237
TI  - N-3 polyunsaturated fatty acids for prevention of postoperative atrial
      fibrillation: updated meta-analysis and systematic review.
AB  - BACKGROUND OR PURPOSE: N-3 polyunsaturated fatty acids (PUFA) have been
      postulated to have an anti-arrhythmic effect on postoperative atrial fibrillation
      (POAF), with conflicting results among studies. This study on pooled data
      evaluated the effect of PUFA on POAF among patients undergoing cardiac surgery.
      METHODS: The Pubmed, EMBASE, and CENTRAL databases were searched without
      restriction on language for randomized controlled trials on the effect of PUFA on
      POAF that were published before August 31, 2017. The incidence of POAF was
      extracted as primary endpoint. Pooled data were assessed by using a random
      effects model. RESULTS: Out of 269 articles identified, 14 studies with 3570
      patients were eligible and included in the meta-analysis. PUFA reduced incidence
      of POAF (RR 0.84 [95% CI 0.73-0.98], P = 0.03). The funnel plot and fail-safe
      number suggested insignificant publication bias. In sensitivity and subgroup
      analyses, (1) PUFA was effective in preventing POAF for eicosapentaenoic acid
      (EPA)/DHA < 1 (0.51 [0.36-0.73], P = 0.0003) but not EPA/DHA > 1 or unknown; (2)
      the efficacy in reducing POAF was apparent when placebo was usual care (0.59
      [0.44-0.80], P = 0.0005), but not when placebo was non-fish oils; and (3) PUFA
      reduced POAF after CABG (0.68 [0.47-0.97], P = 0.03), but not other cardiac
      surgery. CONCLUSIONS: PUFA appears to reduce the incidence of POAF. However, the
      said protective effect may be influenced by EPA/DHA ratio, with < 1 appearing
      preferable. PUFA efficacy on POAF prevention appeared insignificant when compared
      with non-fish oils and only apparent in the setting of CABG alone. Further
      studies are needed to confirm the effect of PUFA on POAF and to assess the proper
      use of PUFA against POAF.

PMID- 29380238
TI  - Activating adenosine A1 receptor accelerates PC12 cell injury via ADORA1/PKC/KATP
      pathway after intermittent hypoxia exposure.
AB  - Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with the
      neurocognitive deficits as a result of the neuronal cell injury. Previous studies
      have shown that adenosine A1 receptor (ADORA1) played an important role against
      hypoxia exposure, such as controlling the metabolic recovery in rat hippocampal
      slices and increasing the resistance in the combined effects of hypoxia and
      hypercapnia. However, little is known about whether ADORA1 takes part in the
      course of neuronal cell injury after intermittent hypoxia exposure which was the
      main pathological characteristic of OSAHS. The present study is performed to
      explore the underlying mechanism of neuronal cell injury which was induced by
      intermittent hypoxia exposure in PC12 cells. In our research, we find that the
      stimulation of the ADORA1 by CCPA accelerated the injury of PC12 cells as well as
      upregulated the expression of PKC, inwardly rectifying potassium channel
      6.2(Kir6.2) and sulfonylurea receptor 1(SUR1) while inhibition of the ADORA1 by
      DPCPX alleviated the injury of PC12 cells as well as downregulated the expression
      of PKC, Kir6.2, and SUR1. Moreover, inhibition of the PKC by CHE, also mitigated
      the injury of PC12 cells, suppressed the Kir6.2 and SUR1 expressions induced by
      PKC. Taken together, our findings indicate that ADORA1 accelerated PC12 cells
      injury after intermittent hypoxia exposure via ADORA1/PKC/KATP signaling pathway.

PMID- 29380239
TI  - VEGF/PKD-1 signaling mediates arteriogenic gene expression and angiogenic
      responses in reversible human microvascular endothelial cells with extended
      lifespan.
AB  - Microvascular ECs (MVECs) are an ideal model in angiogenesis research. The aim of
      this study was to determine vascular endothelial growth factor (VEGF)/protein
      kinase D1 (PKD-1) signaling in expression of arteriogenic genes in human MVECs.
      To achieve this aim, we transduced specific SV40 large T antigen and telomerase
      into primary human dermal MVECs (HMVEC-D) to establish reversible HMVECs with
      extended lifespan (HMVECi-D). HMVECi-D was then exposed to VEGF/VEGF-inducer
      GS4012 or transduced with constitutively active protein kinase PKD-1 (PKD-CA).
      Quantitative RT-PCR was performed to detect arteriogenic gene expression.
      Furthermore, the angiogenic capacity in response to VEGF pathway was evaluated by
      Matrigel tube-formation and proliferation assays. We observed that VEGF/PKD-1
      signaling axis significantly stimulated the expression of arteriogenic genes and
      promoted EC proliferation, along with downregulation of CD36 expression.
      Intriguingly, overexpression of PKD-CA also resulted in formation of tip cell
      morphology, accompanied by increased mRNA of delta-like ligand 4 (DLL4). In
      conclusion, we have successfully established and characterized HMVECi-D, and
      showed that VEGF/PKD-1 signaling axis increases angiogenic and arteriogenic gene
      expression. These studies suggest that the axis may regulate arteriolar
      differentiation through changing MVEC gene expression.

PMID- 29380240
TI  - Calcineurin is an important factor involved in glucose uptake in human
      adipocytes.
AB  - Calcineurin inhibitors are used in immunosuppressive therapy applied after
      transplantation, but they are associated with major metabolic side effects
      including the development of new onset diabetes. Previously, we have shown that
      the calcineurin inhibiting drugs tacrolimus and cyclosporin A reduce adipocyte
      and myocyte glucose uptakes by reducing the amount of glucose transporter type 4
      (GLUT4) at the cell surface, due to an increased internalization rate. However,
      this happens without alteration in total protein and phosphorylation levels of
      key proteins involved in insulin signalling or in the total amount of GLUT4. The
      present study evaluates possible pathways involved in the altered internalization
      of GLUT4 and consequent reduction of glucose uptake provoked by calcineurin
      inhibitors in human subcutaneous adipose tissue. Short- and long-term treatments
      with tacrolimus, cyclosporin A or another CNI deltamethrin (herbicide) decreased
      basal and insulin-dependent glucose uptake in adipocytes, without any additive
      effects observed when added together. However, no tacrolimus effects were
      observed on glucose uptake when gene transcription and protein translation were
      inhibited. Investigation of genes potentially involved in GLUT4 trafficking
      showed only a small effect on ARHGEF11 gene expression (p < 0.05). In conlusion,
      the specific inhibition of calcineurin, but not that of protein phosphatases,
      decreases glucose uptake in human subcutaneous adipocytes, suggesting that
      calcineurin is an important regulator of glucose transport. This inhibitory
      effect is mediated via gene transcription or protein translation; however,
      expression of genes potentially involved in GLUT4 trafficking and endocytosis
      appears not to be involved in these effects.

PMID- 29380241
TI  - Novel ethanocycloheptono [3,4,5-kl]benzo[a]xanthene induces apoptosis in BEL-7402
      cells.
AB  - A novel polycyclic bridged-ring xanthene 2 was synthesized by nucleophilic
      substitution followed by Michael addition reaction between parent dibenzoxanthene
      1 and acetylacetone. The structure of compound 2 was also confirmed by single
      crystal X-ray diffraction. We studied the binding activity of this compound with
      bovine serum albumin (BSA) by fluorescent and UV-visible spectra. The results
      showed that compound had strong binding ability with BSA. Cell viability in five
      tumor cell lines was studied by MTT assay. The cytotoxic effect of bridged-ring
      xanthene 2 against BEL-7402 cells was examined by morphological analyses and
      biochemical assays. Significant nuclear damages of BEL-7402 cells were observed
      after cells were treated with compound in a comet assay. The compound also caused
      DNA damage and S phase arrest in BEL-7402 cells. The efficient induction of
      apoptosis by the compound was confirmed by flow cytometry. Additionally, the
      characteristic nuclear and morphological changes during apoptotic cell death were
      investigated by fluorescent microscopy. The compound 2 enhanced the reactive
      oxygen species (ROS) and decreased the mitochondrial membrane potential. Western
      blot assay indicated that the compound can active caspase-3, caspase-7, down
      regulate the level of Bcl-2, Bcl-x, and up-regulate the level of pro-apoptosis
      protein Bax. The compound 2 induces apoptosis of BEL-7402 cells through a ROS
      mediated mitochondrial dysfunction pathway.

PMID- 29380242
TI  - Comparison of short-term and medium-term swimming training on cardiodynamics and
      coronary flow in high salt-induced hypertensive and normotensive rats.
AB  - The aim of present study was to evaluate the effects of 3- and 6-week swimming
      exercise on cardiodynamics and coronary flow in high salt-induced hypertensive
      and normotensive rats. 80 male Wistar albino rats (6 weeks old) were divided into
      8 groups: hypertensive animals that swam for 3 weeks; hypertensive animals that
      swam for 6 weeks and their respective sedentary controls; normotensive animals
      that swam for 3 weeks; normotensive animals that swam for 6 weeks and their
      respective sedentary controls. Hypertensive animals were on high sodium (8% NaCl
      solution) diet for 4 weeks, and these animals did not drink tap water during the
      experimental protocol. After sacrificing, hearts were isolated and perfused
      according to Langendorff technique at gradually increased coronary perfusion
      pressure (40-120 cmH2O). The following parameters of cardiac function were
      continuously recorded: maximum and minimum rate of pressure development in LV,
      systolic, and diastolic left ventricular pressure, and heart rate. Coronary flow
      was measured flowmetrically. Findings of the present study may help in better
      understanding of short- to medium-term exercise-induced direct effects on cardiac
      function and perfusion. Generally viewed, swimming of both durations did not
      change myocardial function and perfusion in hypertensive and normotensive
      conditions.

PMID- 29380243
TI  - Quercetin exerts an inhibitory effect on cellular bioenergetics of the B164A5
      murine melanoma cell line.
AB  - Modulation of mitochondrial bioenergetics and glycolysis in malignancies has
      recently emerged a potential chemotherapeutic strategy since numerous malignant
      cells have overcome inhibition of the glycolytic pathway by increasing
      mitochondrial ATP production. Quercetin is a flavonoid with antioxidant,
      antiangiogenic, and chemoprotective properties but the mitochondrial effects are
      less characterized. The present study was purported to assess the effects of
      quercetin on the bioenergetic profile of B164A5 murine melanoma cell line. The
      oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were
      measured at 24, 48, and 72 h of treatment of B164A5 murine melanoma cells with
      increasing concentrations (25, 50, 100, and 150 uM) of quercetin using the
      extracellular flux analyzer Seahorse XF24e (Seahorse Agilent). Analysis of
      mitochondrial function was performed in the presence of the classic modulators of
      the electron transport chain: oligomycin, FCCP, and rotenone. 72-h treatment with
      quercetin induced a dose-dependent decrease of all OCR parameters (basal
      respiration, proton leak, ATP turnover, maximal respiration, reserve capacity) as
      well as of ECAR. At variance, 48-h treatment induced a decrease of OCR and ECAR
      when quercetin was applied at 50, 100, and 150 uM, while the 24-h treatment
      induced a decrease of bioenergetic parameters only for the highest concentrations
      (100 and 150 uM) of the compound. Our data clearly demonstrated that quercetin
      elicited dose-dependent inhibitory effect on examined parameters of cellular
      bioenergetics that was most potent at 72 h of treatment. Thereby quercetin,
      modulating both glycolytic and mitochondrial pathways for ATP production, might
      be an efficient approach in killing cancer cells.

PMID- 29380245
TI  - Screening of Potential Inhibitor against Coat Protein of Apple Chlorotic Leaf
      Spot Virus.
AB  - In this study, we analyzed Coat protein (CP) of Apple chlorotic leaf spot virus
      (ACLSV), an important latent virus on Apple. Incidence of the virus is upto 60%
      in various apple cultivars, affecting yield losses of the order of 10-40%
      (depending upon the cultivar). CP plays an important role as the sole building
      block of the viral capsid. Homology approach was used to model 193 amino acid
      sequence of the coat protein. We used various servers such as ConSurf, TargetS,
      OSML, COACH, COFACTOR for the prediction of active site residues in coat protein.
      Virtual screening strategy was employed to search potential inhibitors for CP.
      Top twenty screened molecules considered for drugability, and toxicity analysis
      and one potential molecule was further analyzed by docking analysis. Here, we
      reported a potent molecule which could inhibit the formation of viron assembly by
      targeting the CP protein of virus.

PMID- 29380244
TI  - Immunological impact of Wharton's Jelly mesenchymal stromal cells and natural
      killer cell co-culture.
AB  - Due to their easier isolation, multilineage potential, and immunomodulatory
      capacity, Wharton's Jelly-derived mesenchymal stromal cells (WJ-MSCs) exhibit
      promising efficacy in the field of regenerative medicine and immunotherapy.
      Characterization of WJ-MSCs-natural killer (NK) cells crosstalk is required for
      ameliorating the medicinal value of WJ-MSCs. Here, we revealed that the outcome
      of WJ-MSCs-NK cells crosstalk varied according to the type of cytokines (IL-2, IL
      12, IL-15 and IL-21) utilized to activate NK cells. Differently activated NK
      cells exerted distinct cytotoxicities against WJ-MSCs causing their probable
      death. Cell surface ligands (CD112, CD155, ULPB-3) and receptors (LAIR, CD226,
      CD314, CD335, CD336 and CD337) governing the interaction between NK cells and
      their targets, exhibited altered expression profiles following the co-culture
      with WJ-MSCs. Although partly inhibited NK cell proliferation, WJ-MSCs enhanced
      activated NK-cell-mediated secretion of IFN-gamma and TNF-alpha. Moreover, WJ
      MSCs reinforced NK cells' degranulation as well as secretion of perforin and
      granzymes. On the other hand, WJ-MSCs displayed only slight increase in ROS
      generation but significant decrease in A1 and C1 serpins expression following co
      culture with activated NK cells. Altogether, our results highlight that WJ-MSCs
      NK cells interaction may affect both cell type features and, therefore, their
      therapeutic properties.

PMID- 29380246
TI  - Early Effect of Phonological Information in Korean Visual Word Recognition: An
      ERP Investigation with Transposed Letters.
AB  - The purpose of this study was to examine the role of phonological information on
      visual word recognition by using letter transposition effects. The Korean writing
      system gives a unique opportunity to investigate such phenomenon since the
      transposition of the beginning consonant (onset) and the end consonant (coda) of
      a certain syllable allows one to keep the coda phonology constant while changing
      the written alphabetic characters. In this study, 23 participants' ERPs to such
      transposition cases were compared with the ERPs to cases that do not maintain
      coda phonology while the participants were performing a go/no-go lexical decision
      task for visually presented letter strings. The results of the current study
      showed that transposed materials with original phonological information produce
      less N250 than both the baseline condition and the transposed materials with
      different phonological information condition. The results suggest that
      phonological information is used early in the lexical process in Korean and early
      orthographic processing is influenced by the characteristics of the grapheme to
      phoneme conversion process.

PMID- 29380247
TI  - Examining the Utility of the New Raney Vocabulary Measure Alongside the WAIS-III.
AB  - Psychometric tests related to vocabulary assessments are, for the most part,
      restricted in their use by trained professionals and/or are costly. These
      restrictions limit their use, especially for research purposes. To circumvent
      these limitations, the Raney Vocabulary Measure was created for assessing
      vocabulary proficiency, specifically for research purposes. The measure consists
      of 30 questions where participants were instructed to choose the best definition
      of each word. The purpose of the study was to examine the utility of the new
      measure using the highly standardized but protected Wechsler Adult Intelligence
      Scale. Results from the linear combination of the subscales revealed the
      significant prediction of the Raney Vocabulary Measure, with the Vocabulary
      subtest contributing most to the unique variance. These results support that the
      test examines vocabulary ability. The current results are promising as the test
      would allow for greater accessibility for researchers who do not have access to
      restricted psychometric tests.

PMID- 29380248
TI  - Iron, Dopamine, and alpha-Synuclein Interactions in at-Risk Dopaminergic Neurons
      in Parkinson's Disease.

PMID- 29380249
TI  - Effects of Ketamine on Basal Gamma Band Oscillation and Sensory Gating in
      Prefrontal Cortex of Awake Rats.
AB  - Gamma band oscillation (GBO) and sensory gating (SG) are associated with many
      cognitive functions. Ketamine induces deficits of GBO and SG in the prefrontal
      cortex (PFC). However, the time-courses of the effects of different doses of
      ketamine on GBO power and SG are poorly understood. Studies have indicated that
      GBO power and SG have a common substrate for their generation and abnormalities.
      In this study, we found that (1) ketamine administration increased GBO power in
      the PFC in rats differently in the low- and high-dose groups; (2) auditory SG was
      significantly lower than baseline in the 30 mg/kg and 60 mg/kg groups, but not in
      the 15 mg/kg and 120 mg/kg groups; and (3) changes in SG and basal GBO power were
      significantly correlated in awake rats. These results indicate a relationship
      between mechanisms underlying auditory SG and GBO power.

PMID- 29380250
TI  - Pre-maxillary hypohyperdontia: a report of two cases.
AB  - BACKGROUND: Hypodontia and hyperdontia are considered to be at opposite ends of
      the dental development spectrum. Nevertheless, these anomalies may occur
      concomitantly (hypohyperdontia). CASE REPORT: This clinical report describes two
      case of hypohyperdontia occurring exclusively in the premaxillary region, and the
      difficulties associated with its diagnosis and management. Following 24 months of
      follow-up examinations, Case 1 developed a sequential supernumerary tooth in the
      tooth 35 region. CONCLUSION: Cases of hypohyperdontia can occur exclusively in
      the premaxillary region and may be difficult to diagnose. Multidisciplinary
      treatment planning is essential to facilitate appropriate management, and long
      term follow-up is necessary as sequential supernumerary teeth may develop.

PMID- 29380251
TI  - Safety of Adalimumab Dosed Every Week and Every Other Week: Focus on Patients
      with Hidradenitis Suppurativa or Psoriasis.
AB  - BACKGROUND: Adalimumab is approved for the treatment of hidradenitis suppurativa
      (HS), plaque psoriasis, and other inflammatory conditions. OBJECTIVE: Our
      objective was to examine the safety of adalimumab administered every other week
      (EOW) and every week (EW) in patients with HS and psoriasis and to investigate
      informative data from non-dermatologic indications. METHODS: The safety of
      adalimumab 40-mg EOW versus EW dosing was examined during placebo-controlled and
      open-label study periods in patients with HS (three studies), psoriasis (two
      studies), Crohn's disease (six studies), ulcerative colitis (three studies), and
      rheumatoid arthritis (one study). RESULTS: No new safety risks or increased rates
      of particular adverse events (AEs) were identified with EW dosing. In patients
      with HS or psoriasis, the overall safety of adalimumab 40-mg EOW and EW was
      generally comparable. In studies of adalimumab for non-dermatologic indications,
      including Crohn's disease, ulcerative colitis, and rheumatoid arthritis, the
      overall AE rates were similar for EW and EOW dosing. CONCLUSION: In patients with
      HS or psoriasis, the safety of adalimumab EW and EOW was comparable and
      consistent with the expected adalimumab AE profile. The safety of adalimumab EW
      dosing in patients with dermatologic conditions is supported by data comparing
      adalimumab EW and EOW dosing for Crohn's disease, ulcerative colitis, and
      rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00918255,
      NCT01468207, NCT01468233, NCT00645814, NCT00077779, NCT00055497, NCT01070303,
      NCT00195715, NCT00348283, NCT00385736, NCT00408629, and NCT00573794.

PMID- 29380252
TI  - Newborn Screening Guidelines for Congenital Hypothyroidism in India:
      Recommendations of the Indian Society for Pediatric and Adolescent Endocrinology
      (ISPAE) - Part I: Screening and Confirmation of Diagnosis.
AB  - : The Indian Society for Pediatric and Adolescent Endocrinology has formulated
      locally relevant Clinical Practice Guidelines for newborn screening, diagnosis
      and management of primary congenital hypothyroidism (CH). RECOMMENDATIONS:
      Screening should be done for every newborn using cord blood, or postnatal blood,
      ideally at 48 to 72 h of age. On this screen sample, neonates with TSH > 20 mIU/L
      serum units (or >34 mIU/L for samples taken between 24 to 48 h of age) should be
      recalled for confirmation. For screen TSH > 40 mIU/L, immediate confirmatory
      venous T4/FT4 and TSH, and for milder elevation of screen TSH, a second screening
      TSH at 7 to 10 d of age, should be taken. Preterm and low birth weight infants
      should undergo screening at 48-72 h postnatal age. Sick babies should be screened
      at least by 7 d of age. Venous confirmatory TSH >20 mIU/L before age 2 wk and >10
      mIU/L after age 2 wk, with low T4 (<10 MUg/dL) or FT4 (<1.17 ng/dL) indicate
      primary CH and treatment initiation. Imaging is recommended by radionuclide
      scintigraphy and ultrasonography after CH is biochemically confirmed but
      treatment should not be delayed till scans are performed. Levothyroxine is
      commenced at 10 to 15 MUg/kg in the neonatal period. Serum T4/FT4 is measured at
      2 wk and TSH and T4/FT4 at 1 mo, then 2 monthly till 6 mo, 3 monthly from 6 mo-3
      y and every 3-6 mo thereafter. Babies with the possibility of transient
      congenital hypothyroidism should be re-evaluated at age 3 y, to assess the need
      for lifelong therapy.

PMID- 29380253
TI  - Engineering Thermostable Microbial Xylanases Toward its Industrial Applications.
AB  - Xylanases are one of the important hydrolytic enzymes which hydrolyze the beta-1,
      4 xylosidic linkage of the backbone of the xylan polymeric chain which consists
      of xylose subunits. Xylanases are mainly found in plant cell walls and are
      produced by several kinds of microorganisms such as fungi, bacteria, yeast, and
      some protozoans. The fungi are considered as most potent xylanase producers than
      that of yeast and bacteria. There is a broad series of industrial applications
      for the thermostable xylanase as an industrial enzyme. Thermostable xylanases
      have been used in a number of industries such as paper and pulp industry, biofuel
      industry, food and feed industry, textile industry, etc. The present review
      explores xylanase-substrate interactions using gene-editing tools toward the
      comprehension in improvement in industrial stability of xylanases. The various
      protein-engineering and metabolic-engineering methods have also been explored to
      improve operational stability of xylanase. Thermostable xylanases have also been
      used for improvement in animal feed nutritional value. Furthermore, they have
      been used directly in bakery and breweries, including a major use in paper and
      pulp industry as a biobleaching agent. This present review envisages some of such
      applications of thermostable xylanases for their bioengineering.

PMID- 29380254
TI  - Management of immune thrombocytopenia in multiple sclerosis patients treated with
      alemtuzumab: a Belgian consensus.
AB  - Alemtuzumab (Lemtrada(r)) is a humanized monoclonal antibody indicated for the
      treatment of adult patients with relapsing-remitting multiple sclerosis with
      active disease defined by clinical or imaging features. Alemtuzumab demonstrated
      superior efficacy over active comparator in both treatment naive patients and
      those with inadequate response to prior therapy. Alemtuzumab is associated with a
      consistent and manageable safety and tolerability profile. Treatment with
      alemtuzumab for multiple sclerosis increases the risk for autoimmune adverse
      events including immune thrombocytopenia (ITP). Complete blood counts with
      differential should be obtained prior to initiation of treatment and at monthly
      intervals thereafter for 48 months after the last infusion. After this period of
      time, testing should be performed based on clinical findings suggestive of ITP.
      If ITP onset is confirmed, appropriate medical intervention should be promptly
      initiated, including immediate referral to a specialist. This paper presents the
      consensus of Belgian multiple sclerosis specialists and hematologists to guide
      the treating physician with practical recommendations.

PMID- 29380255
TI  - The Teramoto distal tibial oblique osteotomy (DTOO): surgical technique and
      applicability for ankle osteoarthritis with varus deformity.
AB  - We have devised a medial peri-articular osteotomy, the distal tibial oblique
      osteotomy (DTOO), and have used this technique since 1994 for ankle
      osteoarthritis of advanced and late stages associated with varus inclination.
      This report describes the surgical technique and its applicability. DTOO can be
      used for cases of varus ankle osteoarthritis with a range of the ankle joint
      movement of at least 10 degrees  or more. The osteotomy is obliquely directed cut
      across the distal tibia from proximal-medial to distal lateral and is of an
      opening-wedge type with the centre of rotation coincident with the centre of the
      tibiofibular joint. A laminar spreader instrument is inserted in the osteotomy to
      open the wedge until the lateral surface of the talar body is seen on X-ray to be
      in contact and congruent with medial articular surface of the lateral malleolus.
      Common obstacles which may prevent this contact and congruency are bony spurs
      present on the anterior side of fibula or on the lateral side of the tibia; these
      require removal. The opening-wedge osteotomy is held in position by an Ilizarov
      external fixator or internally fixed with a plate. Bone graft is taken from the
      iliac crest and inserted into the open wedge. If, after completion of the
      osteotomy, the dorsiflexion angle of the ankle joint does not exceed 0 degrees ,
      a Z-lengthening is performed of the Achilles tendon. In the DTOO for ankle
      osteoarthritis, the contact area of the ankle joint increases and decreases the
      load pressure per unit area. Furthermore, as the width of the ankle mortice is
      restored through the realignment of the body of the talus, instability at the
      ankle joint decreases. There is additional improvement with restoration of the
      inclination of the distal tibial articular surface as this directs the hindfoot
      valgus and corrects the alignment of the foot, with consequent improvement of
      ankle pain.

PMID- 29380256
TI  - A novel treatment approach to infected nonunion of long bones without systemic
      antibiotics.
AB  - Infected nonunion of long bones may require intravenous antibiotics over a
      lengthy period which may result in a high rate of complications. This study aims
      to assess the efficacy of local antibiotics used as a replacement to prolonged
      intravenous therapy. Thirteen patients with infected nonunion of long bones who
      failed at least one previous surgery were included. The infection was treated
      through extensive debridement, application of antibiotic-impregnated calcium
      sulphate pellets and the bone stabilized with external fixation. These patients
      were monitored for union and infection by clinical signs, laboratory values, and
      radiographs over a period of 24 months. The results support an eradication of
      infection and union in all patients with no antibiotic-associated complications.
      Local antibiotic delivery using calcium sulphate pellets provides an effective
      method for treatment of nonunion in long bones and is free of the complications
      from the intravenous route.

PMID- 29380257
TI  - Dietary Supplementation with Chromium Picolinate Influences Serum Glucose and
      Immune Response of Brown-Egg Laying Hens.
AB  - To investigate the effect of chromium picolinate (CrPic) on egg production
      performance, egg quality, blood indices, and immune function of laying hens, 270
      23-week-old Beijing Red brown-egg laying hens were randomly assigned to one of
      three treatments with six replicates of 15 birds per replicate for each treatment
      in a completely randomized design. Laying hens were fed a Cr-unsupplemented corn
      soybean meal basal diet (control, containing 0.45 mg Cr/kg by analysis) or the
      basal diet supplemented with 0.4 or 0.6 mg Cr/kg from CrPic for 10 weeks. Laying
      hens fed diets supplemented with CrPic had a lower (P < 0.05) serum glucose (GLU)
      concentration and higher (P < 0.03) serum antibody titer against Newcastle
      disease than those fed the control diet at 33 weeks of age. However, supplemental
      CrPic had no effect (P > 0.05) on egg production and egg quality of brown-egg
      laying hens from 24 to 33 weeks of age. The results from this study indicated
      that supplemental CrPic decreased serum GLU and enhanced the immune function of
      brown-egg laying hens.

PMID- 29380258
TI  - The Influence of Patient-Reported Joint Manifestations on Quality of Life in
      Fabry Patients.
AB  - Fabry disease, a lysosomal storage disorder, is a rare inborn error of metabolism
      caused by deficiency of the enzyme alpha galactosidase A and resulting
      accumulation of globotriaosylceramide. The symptoms of Fabry disease are
      heterogeneous including renal failure, cardiac hypertrophy, and stroke and may
      not be well recognized by non-specialist physicians. Patients with milder, later
      onset of disease often have a delay in diagnosis.Fabry patients may suffer
      significant neuropathic pain in the extremities (acroparasthesia) but the degree
      to which musculoskeletal symptoms contribute to total pain and disability is
      unknown. Here, we present a questionnaire study focusing on joint manifestations
      and their impact on daily life of patients with Fabry disease.Seventy-seven
      patients with Fabry disease and age-matched healthy controls (49 female and 28
      male) took part in a survey focused on joint problems, pain, disability, and
      quality of life. Joint pain and swelling were reported by 43% of male and 39% of
      female Fabry patients. Analysis by age group showed higher prevalence of joint
      problems and decreased quality of life, in terms of mobility, activity, pain, and
      anxiety, in Fabry patients younger than 50 years compared to healthy controls.
      Female Fabry patients had higher fatigue scores compared to control subjects.
      Fabry patients reported problems with vigorous daily activities and
      gripping.Musculoskeletal symptoms are common in Fabry patients and contribute to
      overall pain and decreased quality of life. Awareness of Fabry disease by
      physicians may be raised to ensure timely diagnosis of this rare disease.

PMID- 29380259
TI  - Beneficial Effect of BH4 Treatment in a 15-Year-Old Boy with Biallelic Mutations
      in DNAJC12.
AB  - BACKGROUND: Biallelic mutations in DNAJC12 were recently identified as a BH4
      responsive cause of hyperphenylalaninemia (HPA). Outcome was only favorable when
      treatment was initiated early in life. We report on a 15-year-old boy with HPA
      due to a homozygous deletion in DNAJC12 in whom - despite his advanced age -
      treatment was initiated. CASE: A boy with developmental delay, an extrapyramidal
      movement disorder, and persistently elevated plasma phenylalanine levels was
      diagnosed with DNAJC12 deficiency at the age of 15 years. Diagnosis was made upon
      exome reanalysis revealing a homozygous 6.9 kb deletion in DNAJC12 which had not
      been detected by the standard exome analysis pipeline. Treatment with the BH4
      analog sapropterin dihydrochloride (10 mg/kg/day) was initiated and evoked a 50%
      reduction of the plasma phenylalanine levels. More strikingly, a marked
      improvement in daily functioning and improved exercise tolerance was noted.
      Additionally, gait analysis before and after treatment initiation revealed a
      partial normalization of his movement disorder. CONCLUSION: Patients with
      hyperphenylalaninemia due to DNAJC12 deficiency may benefit from treatment with a
      BH4 analog - even when introduced at a later age.

PMID- 29380260
TI  - Long-term follow-up in the endovascular treatment of intracranial aneurysms with
      flow-diverter stents: update of a single-centre experience.
AB  - INTRODUCTION: Flow-diverter stents are becoming a useful tool in treating
      patients with intracranial aneurysms with suitable anatomical feature. Purpose of
      this study was to evaluate effectiveness and safety of endovascular treatment
      with flow-diverting stents (FD) in unruptured intracranial aneurysms. METHODS:
      From May 2009 and May 2014, we treated 49 patients with a total of 58 aneurysms,
      with FD technique. All patients were treated electively, under general anesthesia
      and were administered single antiplatelet drug 5 days before the procedure and
      double antiplatelet therapy for 3 months afterwards. Fifteen of the patients were
      asymptomatic, eight had headache, thirteen patients presented symptoms due to
      mass effect of the aneurysm on CNS structures, twelve were treated due to a post
      surgical relapse and one patient presented relapsing TIAs due to distal
      embolization from the aneurysm dome. Choice of FD treatment was done according to
      aneurysm anatomy (fusiform over saccular, dome/neck ratio < 2) and whenever
      conventional treatment (coil embolization) appeared difficult (eg. Large aneurysm
      neck, fusiform aneurysms or difficult sac catheterization). We considered a
      dome/neck ratio > 2 as the only exclusion criteria. RESULTS: Successful stent
      deployment was achieved in 50 procedures out of 52 (94.34%) while overall
      mortality was 2% (1/49). Forty-eight patients were evaluated at long-term follow
      up for a total of 56 treated aneurysms. At 3 months, follow-up 75% (42/56) of the
      aneurysms were excluded from intracranial circulation, at 6 months 80.35% (45/56)
      and at 12 months 84% (47/56). Stent patency was observed in 100% of patients at
      short and long-term follow-up, with only two cases of intimal hyperplasia at 3
      months, without any further complications. CONCLUSIONS: According to our study FD
      repair of unruptured intracranial aneurysms appeared to be a safe and effective
      technique, especially in selected patients with hostile anatomy for traditional
      embolization.

PMID- 29380261
TI  - Intracranial arterial calcifications as a prognostic factor for subsequent major
      adverse cardiovascular events (MACE).
AB  - BACKGROUND: Intracranial arterial calcifications (ICAC) are often detected on
      unenhanced CT of patients with an age > 60. However, association with the
      subsequent occurrence of major adverse cardiovascular events (MACE) has not yet
      been evaluated. PURPOSE: This study aimed at evaluating the association of ICAC
      with subsequent MACE and overall mortality. METHODS: In this retrospective, IRB
      approved study, we included 175 consecutive patients (89 males, mean age 78.3 +/-
      8.5 years) of age > 60 years who underwent an unenhanced CT of the head due to
      minor trauma or neurological disorders. Presence of ICAC was determined in seven
      intracranial arteries using a semi-quantitative scale, which resulted in the
      calcified plaque score (CPS). Clinical follow-up information was obtained by
      questionnaires and telephone interviews. MACE was defined as myocardial
      infarction or revascularization, stroke or death due to cardiovascular event.
      RESULTS: Mean follow-up time was 39.8 +/- 7.8 months, resulting in 579.7 patient
      years of follow-up. Overall, 36 MACE occurred during follow-up (annual event rate
      = 6.2%/year). Mean CPS was significantly higher in subjects with MACE during
      follow-up compared to subjects without MACE (p < 0.01). In 15 patients CPS was 0;
      in none of these patients MACE was registered. Kaplan-Meier-analysis revealed
      that patients with a low plaque burden (CPS < 5) had a significant longer MACE
      free and overall survival than patients with a high plaque burden (CPS >= 5) (p <
      0.01). CONCLUSION: Patients with ICAC have an increased risk for future cardio-
      or cerebrovascular events. Therefore, ICAC might be a prognostic factor to
      determine the risk for these events in older patients.

PMID- 29380262
TI  - Multi-slice CT examinations of adult patients at Sudanese hospitals: radiation
      exposure based on size-specific dose estimates (SSDE).
AB  - The aim of this study was to update the radiation exposure for adult patients
      undergoing multi-slice CT (MSCT) examinations using size-specific dose estimates
      (SSDE). Console, displayed CTDIvol and scan parameters were retrospectively
      recorded for 423 adult patients in seven Sudanese hospitals. Patient torso
      diameters were measured using digital calipers on the scanner console. SSDE was
      determined based on transverse images (SSDEtrans) and scout radiographs
      (SSDEsco). Size-specific conversion factors were used to translate the recorded
      CTDIvol into SSDE according to the procedure described in the American
      Association of Physicists in Medicine (AAPM) Report 204. In chest CT, mean
      CTDIvol, SSDEtrans and SSDEsco ranged: from 4.3 to 47.5 mGy (average: 12.8), 5.5
      to 70.3 mGy (average: 18.6) and 5.8 to 63.5 mGy (average: 18.7), respectively. In
      abdominal CT, mean CTDIvol, SSDEtrans and SSDEsco ranged: from 4.0 to 74.5 mGy
      (average: 16), 5.5 to 152.8 mGy (average: 23.9) and 6.0 to 151.3 mGy (average:
      25.21), respectively. Our study highlights the relationships between CT dose and
      patient dimensions measured from scout and transverse CT images. The correlations
      between the patient size and dose based on scout images were less significant
      than that based on transverse images. High dose levels and dose variations among
      hospitals reveal the need for standardization of scanning protocols and staff
      training on adoption of scanners' dose reduction techniques.

PMID- 29380263
TI  - Natively oxidized amino acid residues in the spinach cytochrome b 6 f complex.
AB  - The cytochrome b 6 f complex of oxygenic photosynthesis produces substantial
      levels of reactive oxygen species (ROS). It has been observed that the ROS
      production rate by b 6 f is 10-20 fold higher than that observed for the
      analogous respiratory cytochrome bc1 complex. The types of ROS produced (O2*-,
      1O2, and, possibly, H2O2) and the site(s) of ROS production within the b 6 f
      complex have been the subject of some debate. Proposed sources of ROS have
      included the heme b p , PQ p*- (possible sources for O2*-), the Rieske iron
      sulfur cluster (possible source of O2*- and/or 1O2), Chl a (possible source of
      1O2), and heme c n (possible source of O2*- and/or H2O2). Our working hypothesis
      is that amino acid residues proximal to the ROS production sites will be more
      susceptible to oxidative modification than distant residues. In the current
      study, we have identified natively oxidized amino acid residues in the subunits
      of the spinach cytochrome b 6 f complex. The oxidized residues were identified by
      tandem mass spectrometry using the MassMatrix Program. Our results indicate that
      numerous residues, principally localized near p-side cofactors and Chl a, were
      oxidatively modified. We hypothesize that these sites are sources for ROS
      generation in the spinach cytochrome b 6 f complex.

PMID- 29380264
TI  - Expression and Characterization of Recombinant Sucrose Phosphorylase.
AB  - SPase is widely used in the food, cosmetics, and pharmaceutical industries.
      Previously, a SPase gene was cloned from Bifidobacterium longum JCM1217 and
      constructed into Escherichia coli BL21. In this paper, its expression conditions
      were optimized. The results showed that several induction factors determined the
      expression efficiency of SPase. The initial cell density, IPTG concentration, and
      induction time and temperature significantly (p < 0.01) affected the total
      protein content and activity of expressed SPase. The highest expression
      efficiency was obtained at an initial cell density of OD600 = 0.5, with 0.05 mM
      IPTG, followed by shaking at 180 rpm and incubation at 30  degrees C for 15 h.
      The purified SPase had a specific activity of 122.1 U/mg, which was raised by
      1.85 -fold more than that before optimization, and its recovery yield was 86%.
      Furthermore, SPase also showed higher thermostability. The results of this study
      provide essential information for the industrial production of SPase.

PMID- 29380265
TI  - Utility of the Spanish version of the Everyday Cognition scale in the diagnosis
      of mild cognitive impairment and mild dementia in an older cohort from the
      Argentina-ADNI.
AB  - INTRODUCTION: The performance of activities of daily living in elderly patients
      with memory disorders is directly related to living independently and to
      autonomy. Documenting and assessing functional capacity through detailed scales
      is important for both diagnostic and treatment recommendations. The Everyday
      Cognition (ECog) scale is a relatively new informant-rated measure of cognitive
      and functional abilities. In the present study, the discriminant validity of the
      ECog scale was evaluated in cognitively intact controls (CN) and in patients with
      mild cognitive impairment (MCI) and mild Alzheimer's disease (AD) from the
      Argentina-ADNI cohort to establish diagnostic accuracy. In addition, we compared
      the sensitivity and specificity of ECog against Functional Assessment
      Questionnaire (FAQ) scale to discriminate among the three groups. METHODS: We
      evaluated 15 CN, 28 MCI, and 13 mild AD subjects. External, convergent and
      divergent validity and internal consistency were examined. RESULTS: The average
      total score on the ECog was significantly different across the three diagnostic
      syndromes (p < .05). The ECog was more sensitive than FAQ in discriminating
      between CN and MCI patients and between MCI and AD subjects. The ECog showed a
      strong correlation with FAQ, and moderate correlations with neuropsychological
      tests. Cronbach's alpha was .98. CONCLUSIONS: The ECog scale is an efficient
      instrument for the differentiation of individuals with mild dementia or MCI from
      normal older adults, with good accuracy and good correlation with other tests
      measuring daily and cognitive functions. Comparing against FAQ, ECog was more
      useful in assessing changes in functionality in MCI patients.

PMID- 29380266
TI  - Apparently trivial but serious mistakes: the underestimated risk of a QT
      prolongation.

PMID- 29380267
TI  - Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor
      Antagonist, SUVN-502, in Healthy Young Adults and Elderly Subjects.
AB  - BACKGROUND AND OBJECTIVE: SUVN-502, a selective 5-HT6 receptor antagonist, was
      found to be active in preclinical models of cognitive deterioration suggesting a
      potential role in the treatment of dementia related to Alzheimer's disease. The
      objective of this study was to characterize the safety, tolerability and
      pharmacokinetics of SUVN-502 in healthy young adults and elderly subjects
      following single and multiple oral doses. METHODS: Single doses (5, 15, 50, 100
      and 200 mg SUVN-502) and multiple doses (50, 100 and 130 mg SUVN-502 once daily
      for 7 days) were evaluated in healthy young adults and multiple doses (50 and 100
      mg SUVN-502 once daily for 14 days) were evaluated in elderly subjects using
      randomized, double-blind, placebo-controlled, dose-escalating study designs. The
      effect of food, gender and age on SUVN-502 pharmacokinetics (100 mg single dose)
      was evaluated using an open-label, two-period, randomized, fed and fasted in a
      crossover design. SUVN-502 and M1 (major metabolite of SUVN-502) were monitored
      using validated analytical methods. RESULTS: SUVN-502 is safe and well tolerated
      up to the highest tested single dose of 200 mg in healthy young adults and
      multiple doses up to 130 mg for 7 days and 100 mg for 14 days in healthy young
      adults and elderly subjects, respectively. Exposures of SUVN-502 and M1 were more
      than dose-proportional over the evaluated dose range. Food and gender did not
      have a clinically meaningful effect on SUVN-502 exposure. The mean SUVN-502 total
      (AUC0-infinity, and AUC0-last) and peak exposures (Cmax) were 2.9- and 2.2-fold
      higher, respectively, in elderly subjects compared to young subjects. Steady
      state was achieved for SUVN-502 and M1 within 7 days after once-daily dosing of
      SUVN-502. CONCLUSIONS: SUVN-502 exhibited an acceptable safety, tolerability and
      pharmacokinetic profile in healthy young adults and elderly subjects. Based on
      the above results, 50 and 100 mg once-daily doses of SUVN-502 were advanced to
      Phase 2 evaluation in patients with moderate AD.

PMID- 29380268
TI  - Rapid Characterization of Insulin Modifications and Sequence Variations by
      Proteinase K Digestion and UHPLC-ESI-MS.
AB  - Discovery of novel insulin analogs as therapeutics has remained an active area of
      research. Compared with native human insulin, insulin analog molecules normally
      incorporate either covalent modifications or amino acid sequence variations. From
      the drug discovery and development perspective, methods for efficient and
      detailed characterization of these primary structural changes are very important.
      In this report, we demonstrate that proteinase K digestion coupled with UPLC-ESI
      MS analysis provides a simple and rapid approach to characterize the
      modifications and sequence variations of insulin molecules. A commercially
      available proteinase K digestion kit was used to process recombinant human
      insulin (RHI), insulin glargine, and fluorescein isothiocynate-labeled
      recombinant human insulin (FITC-RHI) samples. The LC-MS data clearly showed that
      RHI and insulin glargine samples can be differentiated, and the FITC
      modifications in all three amine sites of the RHI molecule are well
      characterized. The end-to-end experiment and data interpretation was achieved
      within 60 min. This approach is fast and simple, and can be easily implemented in
      early drug discovery laboratories to facilitate research on more advanced insulin
      therapeutics. Graphical Abstract ?.

PMID- 29380269
TI  - Allocentric Versus Egocentric Spatial Memory in Adults with Autism Spectrum
      Disorder.
AB  - Individuals with autism spectrum disorder (ASD) present difficulties in forming
      relations among items and context. This capacity for relational binding is also
      involved in spatial navigation and research on this topic in ASD is scarce and
      inconclusive. Using a computerised version of the Morris Water Maze task, ASD
      participants showed particular difficulties in performing viewpoint independent
      (allocentric) navigation, leaving viewpoint dependent navigation (egocentric)
      intact. Further analyses showed that navigation deficits were not related to poor
      visual short-term memory or mental rotation in the ASD group. The results further
      confirm the need of autistic individuals for support at retrieval and have
      important implications for the design of signposts and maps.

PMID- 29380270
TI  - Facilitating Neurofeedback in Children with Autism and Intellectual Impairments
      Using TAGteach.
AB  - Individuals with autism and intellectual impairments tend to be excluded from
      research due to their difficulties with methodological compliance. This study
      focuses on using Teaching with Acoustic Guidance-TAGteach-to behaviorally prepare
      children with autism and a IQ <= 80 to participate in a study on neurofeedback
      training (NFT). Seven children (ages 6-8) learned the prerequisite skills
      identified in a task analysis in an average of 5 h of TAGteach training,
      indicating that this is a feasible method of preparing intellectually-impaired
      children with autism to participate in NFT and task-dependent
      electroencephalography measures. TAGteach may thus have the potential to augment
      this population's ability to participate in less accessible treatments and
      behavioral neuroscientific studies.

PMID- 29380271
TI  - A Comparative Analysis of the ADOS-G and ADOS-2 Algorithms: Preliminary Findings.
AB  - The Autism Diagnostic Observation Schedule (ADOS) is a widely utilized
      observational assessment tool for diagnosis of autism spectrum disorders. The
      original ADOS was succeeded by the ADOS-G with noted improvements. More recently,
      the ADOS-2 was introduced to further increase its diagnostic accuracy. Studies
      examining the validity of the ADOS have produced mixed findings, and pooled
      relationship trends between the algorithm versions are yet to be analyzed. The
      current review seeks to compare the relative merits of the ADOS-G and ADOS-2
      algorithms, Modules 1-3. Eight studies met inclusion criteria for the review, and
      six were selected for paired comparisons of the sensitivity and specificity of
      the ADOS. Results indicate several contradictory findings, underscoring the
      importance of further study.

PMID- 29380272
TI  - Local Versus Global Processing in Autism: Special Section Editorial.

PMID- 29380273
TI  - The Changing Safety Net for Low-Income Parents and Their Children: Structural or
      Cyclical Changes in Income Support Policy?
AB  - Refundable tax credits and food assistance are the largest transfer programs
      available to able-bodied working poor and near-poor families in the United
      States, and simultaneous participation in these programs has more than doubled
      since the early 2000s. To understand this growth, we construct a series of two
      year panels from the 1981-2013 waves of the Current Population Survey Annual
      Social and Economic Supplement to estimate the effect of state labor-market
      conditions, federal and state transfer program policy choices, and household
      demographics governing joint participation in food and refundable tax credit
      programs. Overall, changing policy drives much of the increase in the
      simultaneous, biennial use of food assistance and refundable tax credits. This
      stands in stark contrast from the factors accounting for the growth in food
      assistance alone, where cyclical and structural labor market factors account for
      at least one-half of the growth, and demographics play a more prominent role.
      Moreover, since 2000, the business cycle factors as the leading determinant in
      biennial participation decisions in food programs and refundable tax credits,
      suggesting a recent strengthening in the relationship between economic conditions
      and transfer programs.

PMID- 29380274
TI  - Coalescence of droplets laden with insoluble surfactant on a preset liquid film.
AB  - A model for the evolution of two droplets laden with insoluble surfactant
      coalescing on a preset film is established according to the lubrication theory,
      and the coalescence processes are simulated. The role of the surfactant and its
      inherent mechanism are investigated, the effects of the Marangoni number, the
      preset liquid film thickness and the initial spacing between the two droplets on
      the coalescence are examined. The results show that the droplets encounter each
      other, gradually overlap, and finally coalesce into a "new" droplet. The
      Marangoni effect is beneficial to the convergence of the two inner leading fronts
      of the droplets in the early stage, but it hinders the accumulation of the
      droplets and subsequent coalescence. Increasing the Marangoni number promotes not
      only the aforementioned inhibition, but also the convergence of the two leading
      fronts towards the center, which speeds up the coalescence of the surfactant.
      Moreover, the diffusion of the surfactant towards the outsides of the droplets is
      accelerated; hence, its distribution along the droplet surface is more uniform
      after the coalescence. The droplets and the surfactant undertake a longer
      "journey" to achieve coalescence when their initial spacing is increased;
      increasing the preset film thickness shortens the time of coalescence required.

PMID- 29380275
TI  - In Schizophrenia, Depression, Anxiety, and Physiosomatic Symptoms Are Strongly
      Related to Psychotic Symptoms and Excitation, Impairments in Episodic Memory, and
      Increased Production of Neurotoxic Tryptophan Catabolites: a Multivariate and
      Machine Learning Study.
AB  - The depression, anxiety and physiosomatic symptoms (DAPS) of schizophrenia are
      associated with negative symptoms and changes in tryptophan catabolite (TRYCAT)
      patterning. The aim of this study is to delineate the associations between DAPS
      and psychosis, hostility, excitation, and mannerism (PHEM) symptoms, cognitive
      tests as measured using the Consortium to Establish a Registry for Alzheimer's
      Disease (CERAD) and IgA/IgM responses to TRYCATs. We included 40 healthy controls
      and 80 participants with schizophrenia. Depression and anxiety symptoms were
      measured with The Hamilton Depression (HAM-D) and Anxiety (HAM-A) Rating Scales,
      respectively. Physiosomatic symptoms were assessed with the Fibromyalgia and
      Chronic Fatigue Syndrome Rating Scale (FF). Negative symptoms as well as CERAD
      tests, including Verbal Fluency Test (VFT), Mini-Mental State Examination (MMSE),
      Word List Memory (WLM), and WL Delayed Recall were measured, while ratios of IgA
      responses to noxious/protective TRYCATs (IgA NOX_PRO) were computed.
      Schizophrenia symptoms consisted of two dimensions, a first comprising PHEM and
      negative symptoms, and a second DAPS symptoms. A large part of the variance in
      DAPS was explained by psychotic symptoms and WLM. Of the variance in HAM-D, 58.9%
      was explained by the regression on excitement, IgA NOX_PRO ratio, WLM, and VFT;
      29.9% of the variance in HAM-A by psychotic symptoms and IgA NOX/PRO; and 45.5%
      of the variance in FF score by psychotic symptoms, IgA NOX/PRO, and WLM. Neural
      network modeling shows that PHEM, IgA NOX_PRO, WLM, and MMSE are the dominant
      variables predicting DAPS. DAPS appear to be driven by PHEM and negative symptoms
      coupled with impairments in episodic memory, especially false memory creation,
      while all symptom dimension and cognitive impairments may be driven by an
      increased production of noxious TRYCATs, including picolinic, quinolinic, and
      xanthurenic acid.

PMID- 29380276
TI  - Allowance for boundary sharpening in the determination of diffusion coefficients
      by sedimentation velocity: a historical perspective.
AB  - This review summarizes endeavors undertaken in the middle of last century to
      employ the Lamm equation for quantitative analysis of boundary spreading in
      sedimentation velocity experiments on globular proteins, thereby illustrating the
      ingenuity required to achieve that goal in an era when an approximate analytical
      solution of that nonlinear differential equation of second order provided the
      only means for its application. Application of procedures based on that
      approximate solution to simulated sedimentation velocity distributions has
      revealed a slight disparity (about 3%) between returned and input values of the
      diffusion coefficient-a discrepancy comparable with that of estimates obtained by
      current simulative analyses based on numerical solution of the Lamm equation.
      Although the massive technological developments in the gathering and treatment of
      sedimentation velocity data over the past three to four decades have changed
      dramatically the manner in which boundary spreading is analyzed, they have not
      led to any significant improvement in the accuracy of the diffusion coefficient
      thereby deduced.

PMID- 29380277
TI  - First trimester pregnancy ultrasound findings as a function of method of
      conception in an infertile population.
AB  - PURPOSE: The aim of this study was to determine whether first trimester
      ultrasound measurements of crown rump length (CRL) and gestational sac diameter
      (GSD) differ depending on the method of conception among infertile women. METHOD:
      Infertile women, ages 21-50 years old, who conceived viable, singleton
      pregnancies via fresh embryo transfer (ET), frozen ET, non-in vitro fertilization
      (IVF) fertility treatment, or spontaneously were included in this observational
      cohort study at an academic fertility practice. Embryonic growth trajectories
      defined by the CRL and GSD at 6 and 8 weeks' gestation were analyzed and compared
      among the methods of conception. RESULTS: Crown rump length at 6 weeks' gestation
      was smaller for conceptions achieved via fresh ET compared with frozen ET in a
      natural cycle (1.50 vs. 2.50 mm, p = 0.017). Crown rump length was smaller at 8
      weeks' gestation in conceptions achieved via fresh ET compared to frozen ET in a
      programmed cycle (16.13 vs. 17.02 mm, p = 0.039). CONCLUSION: Among infertile
      women, embryo growth may differ between fresh and frozen ET as early as 6 and 8
      weeks' gestation.

PMID- 29380278
TI  - Intra-patient variability in the endometrial receptivity assay (ERA) test.

PMID- 29380279
TI  - Whither human IVF? Fertilisable oocytes selected on the basis of follicular
      temperature.
AB  - Bearing in mind specific parallels between cow and human ovarian physiology, as
      noted in the manuscript, we have measured whether the temperature in a pre
      ovulatory follicle is cooler than that in adjacent tissues. Using a novel
      approach not requiring anaesthetics or surgical procedures, we found that
      follicular fluid bathing cow oocytes shortly before ovulation is cooler than the
      neighbouring uterine surface and cooler than deep rectal temperature (the
      reference body temperature in cattle). By contrast, Graafian follicles of
      comparable size and ultrasonic image that do not subsequently ovulate do not have
      a reduced antral temperature. Human pre-ovulatory follicles have previously been
      reported to be cooler than other ovarian tissues, so the divergence between
      ovulatory and non-ovulatory follicle temperature suggests a valuable addition to
      selection procedures currently used in human in vitro fertilisation (IVF)
      clinics. In future, oocytes to be subjected to IVF might best be those taken from
      cooler follicles. Follicular antral temperature could become a more sensitive
      indicator of oocyte potential that a purely morphological assessment.

PMID- 29380280
TI  - A novel male 2;4;14 complex chromosomal translocation with normal semen
      parameters but 100% embryonic aneuploidy.
AB  - We report a case of a couple with a history of six spontaneous miscarriages in
      which a novel complex chromosomal rearrangement was detected in the male partner
      who had a totally normal semen analysis. Preimplantation genetic testing of their
      embryos demonstrated 100% aneuploidy.

PMID- 29380281
TI  - Retraction Note: Development and In Vitro-In Vivo Characterization of
      Chronomodulated Pulsatile Delivery Formulation of Terbutaline Sulphate by Box
      Behnken Statistical Design.
AB  - This article has been retracted by the journal because the editors have clear
      evidence that the scientific findings in this article are unreliable.

PMID- 29380282
TI  - Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for
      Topical Delivery of Caffeine.
AB  - Cellulite is a dermal disorder including the extracellular matrix, the lymphatic
      and microcirculatory systems and the adipose tissue. Caffeine is used as the
      active moiety depending its preventive effect on localization of fat in the
      cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of
      skin that generates formation and poliferation of new cells having a remarkable
      moisturizing ability. The aim of this study is to formulate HA microparticles
      loaded with caffeine via spray-drying method. Resulting microparticle
      formulations (33.97 +/- 0.3 MUm, span < 2, 88.56 +/- 0.42% encapsulation
      efficiency) were distributed in lecithin organogels to maintain the proper
      viscosity for topical application. Following the characterization and cell
      culture studies, in vitro drug release and ex vivo permeation studies were
      performed. The accumulated amount of caffeine was twice higher than the aqueous
      solution for the microparticle-loaded organogels at 24 h (8262,673 MUg/cm2versus
      4676,691 MUg/cm2). It was related to the sustained behaviour of caffeine release
      from the microparticles. As a result, lecithin organogel containing HA
      encapsulated microparticles could be considered as suitable candidate
      formulations for efficient topical drug delivery system of caffeine. In addition
      to that, synergistic effect of this combination appears as a promising approach
      for long-acting treatment of cellulite.

PMID- 29380283
TI  - Sound changes that lead to seeing longer-lasting shapes.
AB  - To survive, people must construct an accurate representation of the world around
      them. There is a body of research on visual scene analysis, and a largely
      separate literature on auditory scene analysis. The current study follows up
      research from the smaller literature on audiovisual scene analysis. Prior work
      demonstrated that when there is an abrupt size change to a moving object,
      observers tend to see two objects rather than one-the abrupt visual change
      enhances visible persistence of the briefly presented different-sized object.
      Moreover, if a sequence of tones accompanies the moving object, visible
      persistence is enhanced if the tone frequency suddenly changes at the same time
      that the object's size changes. Here, we show that although a sound change must
      occur at roughly the same time as a visual change to enhance visible persistence,
      there is a fairly wide time frame during which the sound change can occur. In
      addition, the impact of a sound change on visible persistence is not simply
      matter of the physical pattern: The same pattern of sound can enhance visible
      persistence or not, depending on how the pattern is itself perceived.
      Specifically, a change in a tone's frequency can enhance visible persistence when
      it accompanies a visual size change, but the same frequency change will not do so
      if the shift is embedded in a larger pattern that makes the change merely a
      continuation of alternating frequencies. The current study supports a scene
      analysis process that is both multimodal and actively constructive.

PMID- 29380284
TI  - 123I-mIBG: Simplicity and reproducibility.

PMID- 29380285
TI  - Stronger correlation with myocardial ischemia of high-sensitivity troponin T than
      other biomarkers.
AB  - BACKGROUND: Acute myocardial infarction (AMI) is considered a major cause of
      death and disability. Myocardial perfusion scintigraphy (MPS) as a non-invasive
      diagnostic imaging procedure and certain biomarkers associated with myocardial
      ischemia (ISCH), such as ischemia-modified albumin (IMA), neuropeptide Y (NPY), N
      terminal pro b-type natriuretic peptide (NT-proBNP), and high-sensitivity
      troponin T (hsTnT) could probably aid in the detection of myocardial infarction.
      METHODS: Between December 2011 and June 2012, we prospectively analyzed patients
      who underwent a MPS study with the clinical question of myocardial ISCH. An
      exercise test was performed along with a MPS. Blood was drawn from the patients
      before exercise and the within 3 minutes from achieving maximum load and was
      analyzed for the aforementioned biomarkers. RESULTS: A total of 71 patients (56
      men and 15 women) were enrolled with a mean age of 61 +/- 12 years. Twenty-six
      patients (36.6%) showed reduced uptake on stress MPS images that normalized at
      rest, a finding consistent with ISCH. Between ISCH and non-ISCH groups, only
      hsTnT levels showed a significant difference with the highest levels pertaining
      to the former group both before (0.0075 ng/ml vs 0.0050 ng/ml, P = 0.023) and
      after stress exercise (0.0085 vs 0.0050, P = 0.015). The most prominent
      differences were seen in higher stages of the Bruce protocol (stress duration >
      9.05 minutes - P < 0.017). None of the IMA, NPY, and NP-pro BNP showed
      significant differences in time between the two groups. CONCLUSIONS: Although
      IMA, NPY, and NT-pro BNP may not detect minor ischemic myocardial insults, serum
      hsTnT holds a greater ability of detecting not only myocardial infarction but
      also less severe ischemia. Further studies with larger cohorts of patients are
      warranted in order to better define the role of hsTnT as a screening tool for
      myocardial ischemia.

PMID- 29380286
TI  - Diagnostic value of stress thallium-201/rest technetium-99m-sestamibi sequential
      dual isotope high-speed myocardial perfusion imaging for the detection of
      haemodynamically relevant coronary artery stenosis.
AB  - BACKGROUND: The aim of this study was to determine the diagnostic accuracy of
      stress thallium-201/rest technetium-99m-sestamibi sequential dual-isotope high
      speed myocardial perfusion imaging (DI-HS-MPI) against invasively determined
      fractional flow reserve (FFR). METHODS: Fifty-four consecutive patients
      prospectively underwent DI-HS-MPI before invasive coronary angiography. Perfusion
      was scored visually by summed stress score on a patient and coronary territory
      basis. Significant coronary artery disease (CAD) was defined by the presence of
      >= 90% stenosis/occlusion or fractional flow reserve <= 0.80 for coronary
      stenosis >= 50%. RESULTS: FFR was measured in 69 of 162 coronary vessels, with
      1.28 +/- 0.56 vessels assessed/patient. Sensitivity, specificity, and diagnostic
      accuracy of MPI for the detection of significant CAD were 92.8%, 69.2%, and
      81.4%, on a patient basis, and 83.7%, 90.4%, and 88.8% by coronary territory.
      CONCLUSIONS: DI-HS-MPI accurately detects functionally significant CAD as defined
      by using FFR.

PMID- 29380287
TI  - Overview of Current Drugs and Molecules in Development for Spinal Muscular
      Atrophy Therapy.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily
      characterized by a loss of spinal motor neurons, leading to progressive paralysis
      and premature death in the most severe cases. SMA is caused by homozygous
      deletion of the survival motor neuron 1 (SMN1) gene, leading to low levels of SMN
      protein. However, a second SMN gene (SMN2) exists, which can be therapeutically
      targeted to increase SMN levels. This has recently led to the first disease
      modifying therapy for SMA gaining formal approval from the US Food and Drug
      Administration (FDA) and European Medicines Agency (EMA). Spinraza (nusinersen)
      is a modified antisense oligonucleotide that targets the splicing of SMN2,
      leading to increased SMN protein levels, capable of improving clinical phenotypes
      in many patients. In addition to Spinraza, several other therapeutic approaches
      are currently in various stages of clinical development. These include SMN
      dependent small molecule and gene therapy approaches along with SMN-independent
      strategies, such as general neuroprotective factors and muscle strength-enhancing
      compounds. For each therapy, we provide detailed information on clinical trial
      design and pharmacological/safety data where available. Previous clinical studies
      are also discussed to provide context on SMA clinical trial development and the
      insights these provided for the design of current studies.

PMID- 29380288
TI  - Ledipasvir/Sofosbuvir: A Review in Chronic Hepatitis C.
AB  - Oral once-daily, fixed-dose, ledipasvir/sofosbuvir (Harvoni(r)) [+/- ribavirin]
      is approved in several countries for the treatment of chronic hepatitis C (CHC)
      in adults and adolescents aged 12 to < 18 years, with direct-acting antiviral
      (DAA) regimens resulting in a paradigm shift in the treatment of the disease. In
      the clinical trial and/or clinical practice setting, ledipasvir/sofosbuvir (+/-
      ribavirin) was associated with high sustained virological response rates 12 weeks
      post-treatment (SVR12) in treatment-naive and -experienced adults and adolescents
      with chronic hepatitis C virus (HCV) genotype (GT) 1 infection, including in
      those with compensated cirrhosis or who were co-infected with HIV. SVR12 rates in
      real-world studies were consistent with those in trials. In other trials,
      ledipasvir/sofosbuvir (+/- ribavirin) was associated with high SVR12 rates in
      various CHC populations, including patients with HCV GT2, 3, 4, 5 or 6 infection,
      cirrhosis, pre and/or post liver or renal transplantation, inherited blood
      disorders or failure after prior DAA and/or interferon therapy. Thus,
      ledipasvir/sofosbuvir (+/- ribavirin) is a valuable effective and generally well
      tolerated option for adolescent and adult patients with HCV GT1, 4, 5 or 6
      infection, including those with HIV co-infection or cirrhosis, with evidence also
      supporting its use in patients with chronic HCV GT2 or 3 infection.

PMID- 29380290
TI  - MenB-FHbp Meningococcal Group B Vaccine (Trumenba(r)): A Review in Active
      Immunization in Individuals Aged >= 10 Years.
AB  - MenB-FHbp (bivalent rLP2086; Trumenba(r)) is a recombinant protein-based vaccine
      targeting Neisseria meningitidis serogroup B (MenB), which has recently been
      licensed in the EU for active immunization to prevent invasive disease caused by
      MenB in individuals >= 10 years of age. The vaccine, which contains a variant
      from each of the two identified subfamilies of the meningococcal surface protein
      factor H-binding protein (fHBP), has been licensed in the USA for active
      immunization in individuals 10-25 years of age since 2014. This article reviews
      the immunogenicity, reactogenicity and tolerability of MenB-FHbp, with a focus on
      the EU label and the European setting. As demonstrated in an extensive program of
      clinical trials in adolescents and young adults, a two-dose or three-dose series
      of MenB-FHbp elicits a strong immune response against a range of MenB test
      strains selected to be representative of strains prevalent in Europe and the USA.
      Follow-up studies investigating the persistence of the MenB-FHbp immune response
      and the effect of a booster dose of the vaccine indicate that a booster dose
      should be considered (following a primary vaccine series) in individuals at
      continued risk of invasive meningococcal disease. MenB-FHbp vaccine appears to be
      moderately reactogenic but, overall, is generally well tolerated, with most
      adverse reactions being mild to moderate in severity. Although post-marketing,
      population-based data will be required to establish the true effectiveness of the
      vaccine, currently available data indicate that MenB-FHbp, in a two-dose or three
      dose series, is likely to provide broad protection against MenB strains
      circulating in Europe.

PMID- 29380289
TI  - Prevention and Treatment of Chronic Postsurgical Pain: A Narrative Review.
AB  - Chronic postsurgical pain affects between 5 and 75% of patients, often with an
      adverse impact on quality of life. While the transition of acute to chronic pain
      is a complex process-involving multiple mechanisms at different levels-the
      current strategies for prevention have primarily been restricted to perioperative
      pharmacological interventions. In the present paper, we first present an up-to
      date narrative literature review of these interventions. In the second section,
      we develop several ways by which we could overcome the limitations of the current
      approaches and enhance the outcome of our surgical patients, including the better
      identification of individual risk factors, tailoring treatment to individual
      patients, and improved acute and subacute pain evaluation and management. The
      third and final section covers the treatment of established CPSP. Given that
      evidence for the current therapeutic options is limited, we need high-quality
      trials studying multimodal interventions matched to pain characteristics.

PMID- 29380291
TI  - Neural correlates of three cognitive processes involved in theory of mind and
      discourse comprehension.
AB  - Neuroimaging studies have found that theory of mind (ToM) and discourse
      comprehension involve similar brain regions. These brain regions may be
      associated with three cognitive components that are necessarily or frequently
      involved in ToM and discourse comprehension, including social concept
      representation and retrieval, domain-general semantic integration, and domain
      specific integration of social semantic contents. Using fMRI, we investigated the
      neural correlates of these three cognitive components by exploring how discourse
      topic (social/nonsocial) and discourse processing period (ending/beginning)
      modulate brain activation in a discourse comprehension (and also ToM) task.
      Different sets of brain areas showed sensitivity to discourse topic, discourse
      processing period, and the interaction between them, respectively. The most novel
      finding was that the right temporoparietal junction and middle temporal gyrus
      showed sensitivity to discourse processing period only during social discourse
      comprehension, indicating that they selectively contribute to domain-specific
      semantic integration. Our finding indicates how different domains of semantic
      information are processed and integrated in the brain and provides new insights
      into the neural correlates of ToM and discourse comprehension.

PMID- 29380292
TI  - Oscillatory brain activity differentially reflects false belief understanding and
      complementation syntax processing.
AB  - False belief understanding (FBU) enables people to consider conflicting beliefs
      about the same situation. While language has been demonstrated to be a correlate
      of FBU, there is still controversy about the extent to which a specific aspect of
      language, complementation syntax, is a necessary condition for FBU. The present
      study tested an important notion from the debate proposing that complementation
      syntax task is redundant to FBU measures. Specifically, we examined
      electrophysiological correlates of false belief, false complementation, and their
      respective true conditions in adults using electroencephalography (EEG), focusing
      on indices of oscillatory brain activity and large-scale connectivity. The
      results showed strong modulation of parieto-occipital alpha (8-12 Hz) and beta
      (13-20 Hz) power by the experimental manipulations, with heightened sustained
      alpha power reflective of effortful internal processing observed in the false
      compared to the true conditions and reliable beta power reductions sensitive to
      mentalizing and/or syntactic demands in the belief versus the complementation
      conditions. In addition, higher coupling between parieto-occipital regions and
      widespread frontal sites in the beta band was found for the false-belief
      condition selectively. The result of divergence in beta oscillatory activity and
      in connectivity between false belief and false complementation does not support
      the redundancy hypothesis.

PMID- 29380293
TI  - Frontal cortex electrophysiology in reward- and punishment-related feedback
      processing during advice-guided decision making: An interleaved EEG-DC
      stimulation study.
AB  - During decision making, individuals are prone to rely on external cues such as
      expert advice when the outcome is not known. However, the electrophysiological
      correlates associated with outcome uncertainty and the use of expert advice are
      not completely understood. The feedback-related negativity (FRN), P3a, and P3b
      are event-related brain potentials (ERPs) linked to dissociable stages of
      feedback and attentional processing during decision making. Even though these
      ERPs are influenced by both reward- and punishment-related feedback, it remains
      unclear how extrinsic information during uncertainty modulates these brain
      potentials. In this study, the effects of advice cues on decision making were
      investigated in two separate experiments. In the first experiment,
      electroencephalography (EEG) was recorded in healthy volunteers during a decision
      making task in which the participants received reward or punishment feedback
      preceded by novice, amateur, or expert advice. The results showed that the P3a
      component was significantly influenced by the subjective predictive value of an
      advice cue, whereas the FRN and P3b were unaffected by the advice cues. In the
      second, sham-controlled experiment, cathodal transcranial direct current
      stimulation (ctDCS) was administered in conjunction with EEG in order to explore
      the direct contributions of the frontal cortex to these brain potentials. Results
      showed no significant change in either advice-following behavior or decision
      times. However, ctDCS did decrease FRN amplitudes as compared to sham, with no
      effect on the P3a or P3b. Together, these findings suggest that advice
      information may act primarily on attention allocation during feedback processing,
      whereas the electrophysiological correlates of the detection and updating of
      internal prediction models are not affected.

PMID- 29380294
TI  - Reduction of implicit cognitive bias with cathodal tDCS to the left prefrontal
      cortex.
AB  - Implicit associations can interfere with cognitive operations and behavioral
      decisions without direct intention. Enhancement of neural activity with anodal
      transcranial direct current stimulation (tDCS) was proposed to reduce implicit
      associations by means of improved cognitive control. However, a targeted
      reduction of distractive implicit associations by inhibitory cathodal tDCS,
      recently shown in spatial-numerical associations, provides an interesting
      alternative approach to support goal-directed behavior with transcranial brain
      stimulation. To test this rationale with a sham-controlled cross-over design, a
      standardized Implicit Association Test (IAT) was performed by 24 healthy
      participants parallel to 1 mA cathodal or sham tDCS to the left prefrontal
      cortex. In this double-classification task, insect versus flower pictures and
      negative versus positive words are mapped together onto two shared response keys
      with crossed response assignments in separate blocks. Responses were faster when
      insect + negative and flower + positive stimuli required the same answer (IAT
      effect). Most critically, the IAT effect was reduced during cathodal tDCS as
      compared to sham stimulation. Thus, results are consistent with the proposed
      stimulation rationale, with previous observations, and complementary to previous
      studies using different tDCS configurations.

PMID- 29380295
TI  - Nitrile Metabolizing Enzymes in Biocatalysis and Biotransformation.
AB  - Nitrile metabolizing enzymes, i.e., aldoxime dehydratase, hydroxynitrile lyase,
      nitrilase, nitrile hydratase, and amidase, are the key catalysts in carbon
      nitrogen triple bond anabolism and catabolism. Over the past several years, these
      enzymes have drawn considerable attention as prominent biocatalysts in academia
      and industries because of their wide applications. Research on various aspects of
      these biocatalysts, i.e., sources, screening, function, purification, molecular
      cloning, structure, and mechanisms, has been conducted, and bioprocesses at
      various scales have been designed for the synthesis of myriads of useful
      compounds. This review is focused on the potential of nitrile metabolizing
      enzymes in the production of commercially important fine chemicals such as
      nitriles, carboxylic acids, and amides. A number of opportunities and challenges
      of nitrile metabolizing enzymes in bioprocess development for the production of
      bulk and fine chemicals are discussed.

PMID- 29380296
TI  - A Novel 2-Keto-D-Gluconic Acid High-Producing Strain Arthrobacter globiformis
      JUIM02.
AB  - 2-Keto-D-gluconic acid (2KGA) is mainly used for industrial production of
      erythorbic acid, a food antioxidant. In this study, a 2KGA producing strain
      JUIM02 was firstly identified as Arthrobacter globiformis by morphological
      observation and 16S rDNA sequencing. The 2KGA synthetic capacity of A.
      globiformis JUIM02 was evaluated by both fermentation and bioconversion, with 180
      g/L dextrose monohydrate as substrates, in shake flasks and 5 L fermenters. For
      fermentation, 2KGA titer, yield, molar yield, and productivity of JUIM02 reached
      159.05 g/L, 0.97 g/g, 90.18%, and 6.63 g/L/h in 24 h. For non-sterile and buffer
      free bioconversion by free resting cells (~ 3.2 g/L dry cell weight) of JUIM02,
      these data were 172.96 g/L, 1.06 g/g, 98.07%, and 5.41 g/L/h in 32 h. Moreover,
      JUIM02 resting cells could be repeatedly used. Resting cells stored at 4  degrees
      C within 30 days showed stable bioconversion capacity, with 2KGA titers >= 171.50
      g/L, yields >= 1.04 g/g, and molar yields >= 97.24%. The 2KGA synthetic pathway
      in A. globiformis, which was rarely reported, was also speculated similar to
      Pseudomonas and verified preliminarily. In conclusion, A. globiformis JUIM02 is a
      promising 2KGA industrial-producing strain suitable for various production
      methods and a suitable object for 2KGA metabolism research of A. globiformis.

PMID- 29380299
TI  - Jerome Dargent, MD.

PMID- 29380298
TI  - Isolation and characterization of the primary epithelial breast cancer cells and
      the adjacent normal epithelial cells from Iranian women's breast cancer tumors.
AB  - As an experimental model, most studies rely on established human cancer cell
      lines; however, some genetical or phenotypical differences exist between these
      cells and their original tumor. Therefore, primary cells isolated directly from
      tissue are believed to be more biologically relevant tools for studying human and
      animal biology. Here, we aimed to isolate primary epithelial cancer and normal
      cells from breast tumors of Iranian women, for the first time. Thus, we isolated
      the epithelial and fibroblast cells from biopsy samples of patients with breast
      cancer based on differential centrifugation followed by culture in selective
      media. Normal epithelial cells obtained from the tissue biopsy away from the core
      of the tumor, based on the pathological diagnosis. Flow cytometry analysis
      indicated the positive immunoreactivity of the isolated epithelial cells against
      CD24 and Epithelial Specific Antigen (ESA/EpCAM), while they displayed a
      concomitant low expression of CD44 and CD49f. In contrat to fibroblasts, the qPCR
      data indicated the expression of luminal intracellular cytokeratin (Ck18) in both
      normal and cancer epithelial cells, but there was no expression of
      myoepithelial/basal markers, CK5 and vimentin. The epithelial cancer cells were
      reactive to cytokeratin 19 (CK19) antibody, whereas the normal epithelial cells
      were not. The expression of calmodulin-like protein (CLP) was also lower in the
      cancer epithelial cells than in the normal ones. In conclusion, primary
      epithelial normal and cancer cells, in addition to the fibroblasts were isolated
      and characterized from breast tumor of Iranian patients; and CLP expression is
      suggested as a susceptibility marker for breast cancer screening.

PMID- 29380300
TI  - Preoperative Prediction of Small Bowel Length Using CT Scan and Tridimensional
      Reconstructions: a New Tool in Bariatric Surgery?
AB  - PURPOSE: During Roux-en-Y-gastric Bypass, the limb lengths are preoperatively
      determined regardless of individual small bowel length (SBL), which presents a
      great variability. Few studies highlighted anthropometric factors associated with
      SBL, and none attempted to predict SBL preoperatively. OBJECTIVE: The aim of this
      study is to evaluate factors correlated to SBL (anthropometric and radiologic)
      and to establish a preoperative SBL prediction. MATERIAL AND METHODS: In this
      single-center prospective study, 30 adult patients who underwent laparotomy with
      a preoperative CT scan were included. Intraoperative SBL measurement was
      performed with an umbilical tape. Anthropometric parameters were age, gender,
      height, and BMI. 2D radiological measurements consisted of subcutaneous
      thickness, abdominal diameters, waist circumference, and mesenteric root length.
      3D radiological volumetric reconstructions consisted of whole small bowel and
      mesentery (WSBM), lean small bowel and mesentery (LSBM), and fat small bowel and
      mesentery (FSBM). RESULTS: Mean intraoperative measurement of SBL was 531 +/- 105
      cm. Among the clinical and radiological measurements, the FSBM volume presented
      the greatest dispersion. Height (p < 0.02) and LSBM volume (p < 0.01) were
      significantly correlated to the SBL in univariate analysis. LSBM volume was the
      only measurement significantly associated with SBL in multivariate analysis (p <
      0.006). From the multivariate model, a formula was created to predict SBL. The
      mean percentage difference between predicted and intraoperative SBL measurements
      for all patients was 13.7%, and 8.4% for obese patients. CONCLUSION: LSBM volume
      is significantly correlated to the SBL. A preoperative SBL prediction with low
      percentage error could be performed with LSBM volume.

PMID- 29380301
TI  - AlignTool: The automatic temporal alignment of spoken utterances in German,
      Dutch, and British English for psycholinguistic purposes.
AB  - In language production research, the latency with which speakers produce a spoken
      response to a stimulus and the onset and offset times of words in longer
      utterances are key dependent variables. Measuring these variables automatically
      often yields partially incorrect results. However, exact measurements through the
      visual inspection of the recordings are extremely time-consuming. We present
      AlignTool, an open-source alignment tool that establishes preliminarily the onset
      and offset times of words and phonemes in spoken utterances using Praat, and
      subsequently performs a forced alignment of the spoken utterances and their
      orthographic transcriptions in the automatic speech recognition system MAUS.
      AlignTool creates a Praat TextGrid file for inspection and manual correction by
      the user, if necessary. We evaluated AlignTool's performance with recordings of
      single-word and four-word utterances as well as semi-spontaneous speech.
      AlignTool performs well with audio signals with an excellent signal-to-noise
      ratio, requiring virtually no corrections. For audio signals of lesser quality,
      AlignTool still is highly functional but its results may require more frequent
      manual corrections. We also found that audio recordings including long silent
      intervals tended to pose greater difficulties for AlignTool than recordings
      filled with speech, which AlignTool analyzed well overall. We expect that by semi
      automatizing the temporal analysis of complex utterances, AlignTool will open new
      avenues in language production research.

PMID- 29380297
TI  - Epidemiology of fungal infections in China.
AB  - With the increasing number of immunocompromised hosts, the epidemiological
      characteristics of fungal infections have undergone enormous changes worldwide,
      including in China. In this paper, we reviewed the existing data on mycosis
      across China to summarize available epidemiological profiles. We found that the
      general incidence of superficial fungal infections in China has been stable, but
      the incidence of tinea capitis has decreased and the transmission route has
      changed. By contrast, the overall incidence of invasive fungal infections has
      continued to rise. The occurrence of candidemia caused by Candida species other
      than C. albicans and including some uncommon Candida species has increased
      recently in China. Infections caused by Aspergillus have also propagated in
      recent years, particularly with the emergence of azole-resistant Aspergillus
      fumigatus. An increasing trend of cryptococcosis has been noted in China, with
      Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant
      pathogen. Retrospective studies have suggested that the epidemiological
      characteristics of Pneumocystis pneumonia in China may be similar to those in
      other developing countries. Endemic fungal infections, such as sporotrichosis in
      Northeastern China, must arouse research, diagnostic, and treatment vigilance.
      Currently, the epidemiological data on mycosis in China are variable and
      fragmentary. Thus, a nationwide epidemiological research on fungal infections in
      China is an important need for improving the country's health.

PMID- 29380302
TI  - Split liver technique with middle hepatic vein reconstruction on livers from
      transplant hepatectomies: a useful tool for surgical improvement.
AB  - Livers removed during transplant hepatectomies could represent a useful anatomic
      ex vivo resource for surgical training, since they are intact and not altered by
      post-mortem changes yet. The aim of this study is to investigate the
      effectiveness of such kind of surgical training applied on some hepatic surgery
      techniques. In the present paper, we focused on split liver operation and middle
      hepatic vein (MHV) bipartition/reconstruction, since these procedures have a
      quite long learning curve. Seven native livers were submitted to split liver
      procedure by a senior resident assisted by a fully trained hepatic surgeon. Pre
      splitting ultrasound mapping was compared to pre-operative CT scan. The whole
      graft was divided into two hemi-livers and the MHV into two hemi-confluents and
      reconstructed by venous or arterial patches obtained by deceased donor iliac
      homograft. Water tightness of the anastomosis was confirmed by hydro-pneumatic
      test and bench portal perfusion. Reduction in operating time was considered an
      indirect indicator of surgical skill improvement. In all cases, the US confirmed
      the anatomical distribution of MHV tributaries observed by pre-transplant CT
      scan. The "ex situ" splitting procedures and MHV bipartition and reconstruction
      were performed in all native livers in the usual time required for liver
      transplantation bench surgery (range 50-75 min). Liver grafts removed during
      hepatectomy could represent a useful resource of intact organs to perform
      surgical training and boost surgical confidence. In our initial experience, the
      study of venous drainage of the MHV and application of liver splitting technique
      and MHV reconstruction resulted technically feasible.

PMID- 29380304
TI  - Nutritional Programming Effects on Development of Metabolic Disorders in Later
      Life.
AB  - Developmental programming resulting from maternal malnutrition can lead to an
      increased risk of metabolic disorders such as obesity, insulin resistance, type 2
      diabetes and cardiovascular disorders in the offspring in later life.
      Furthermore, many conditions linked with developmental programming are also known
      to be associated with the aging process. This review summarizes the available
      evidence about the molecular mechanisms underlying these effects, with the
      potential to identify novel areas of therapeutic intervention. This could also
      lead to the discovery of new treatment options for improved patient outcomes.

PMID- 29380305
TI  - Effects of Prenatal Nutrition and the Role of the Placenta in Health and Disease.
AB  - Epidemiologic studies identified the linkage between exposures to stresses,
      including the type and plane of nutrition in utero with development of disease in
      later life. Given the critical roles of the placenta in mediating transport of
      nutrients between the mother and fetus and regulation of maternal metabolism,
      recent attention has focused on the role of the placenta in mediating the effect
      of altered nutritional exposures on the development of disease in later life. In
      this chapter we describe the mechanisms of nutrient transport in the placenta,
      the influence of placental metabolism on this, and how placental energetics
      influence placental function in response to a variety of stressors. Further the
      recent "recognition" that the placenta itself has a sex which affects its
      function may begin to help elucidate the mechanisms underlying the well-known
      dimorphism in development of disease in adult life.

PMID- 29380306
TI  - Developmental Origins of Stress and Psychiatric Disorders.
AB  - Over the last few decades, evidence has emerged that the pathogenesis of
      psychiatric disorders such as schizophrenia can involve perturbations of the
      hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems.
      Variations in the manifestation of these effects could be related to differences
      in clinical symptoms between affected individuals and to differences in treatment
      response. Such effects can also arise from the complex interaction between genes
      and environmental factors. Here, we review the effects of maternal stress on
      abnormalities in HPA axis regulation and the development of psychiatric disorders
      such as schizophrenia. Studies in this area may prove critical for increasing our
      understanding of the multidimensional nature of mental disorders and could lead
      to the development of improved diagnostics and novel therapeutic approaches for
      treating individuals who suffer from these conditions.

PMID- 29380303
TI  - Gut Microbiota and the Neuroendocrine System.
AB  - The microbial ecosystem that inhabits the gastrointestinal tract of all mammals
      the gut microbiota-has been in a symbiotic relationship with its hosts over many
      millennia. Thanks to modern technology, the myriad of functions that are
      controlled or modulated by the gut microbiota are beginning to unfold. One of the
      systems that is emerging to closely interact with the gut microbiota is the
      body's major neuroendocrine system that controls various body processes in
      response to stress, the hypothalamic-pituitary-adrenal (HPA) axis. This
      interaction is of pivotal importance; as various disorders of the microbiota-gut
      brain axis are associated with dysregulation of the HPA axis. The present
      contribution describes the bidirectional communication between the gut microbiota
      and the HPA axis and delineates the potential underlying mechanisms. In this
      regard, it is important to note that the communication between the gut microbiota
      and the HPA axis is closely interrelated with other systems, such as the immune
      system, the intestinal barrier and blood-brain barrier, microbial metabolites,
      and gut hormones, as well as the sensory and autonomic nervous systems. These
      communication pathways will be exemplified through preclinical models of early
      life stress, beneficial roles of probiotics and prebiotics, evidence from germ
      free mice, and antibiotic-induced modulation of the gut microbiota.

PMID- 29380307
TI  - Proteomic Studies of Psychiatric Disorders.
AB  - Many diseases result from programming effects in utero. This chapter describes
      recent advances in proteomic studies which have improved our understanding of the
      underlying pathophysiological pathways in the major psychiatric disorders,
      resulting in the development of potential novel biomarker tests. Such tests
      should be based on measurement of blood-based proteins given the ease of
      accessibility of this medium and the known connections between the periphery and
      the central nervous system. Most importantly, emerging biomarker tests should be
      developed on lab-on-a-chip and other handheld devices to enable point-of-care
      use. This should help to identify individuals with psychiatric disorders much
      sooner than ever before, which will allow more rapid treatment options for the
      best possible patient outcomes.

PMID- 29380308
TI  - Developmental Origins of Breast Cancer: A Paternal Perspective.
AB  - The developmental origins of breast cancer have been considered predominantly
      from a maternal perspective. Although accumulating evidence suggests a paternal
      programming effect on metabolic diseases, the potential impact of fathers'
      experiences on their daughters' breast cancer risk has received less attention.
      In this chapter, we focus on the developmental origins of breast cancer and
      examine the emerging evidence for a role of fathers' experiences.

PMID- 29380309
TI  - Point-of-Care Testing and Personalized Medicine for Metabolic Disorders.
AB  - This chapter describes innovations in biomarker testing that can facilitate
      earlier and better treatment of patients who suffer from metabolic disorders. The
      use of new microfluidic devices along with miniaturized biosensors and
      transducers enables analysis of a single drop of a blood within the time frame of
      a typical visit to a doctor's office. Steps are underway so that these approaches
      will incorporate both biochemical and clinical data, resulting in unique
      bioprofiles for each patient. This will allow earlier, personalized, and more
      effective therapeutic options. In addition, smartphone apps for self-monitoring
      will be used increasingly for the best possible patient outcomes.

PMID- 29380310
TI  - Pregnancy and Lactation: A Window of Opportunity to Improve Individual Health.
AB  - Human and animal studies indicate that obesity during pregnancy adversely impacts
      both maternal health and offspring phenotype predisposing them to chronic
      diseases later in life including obesity, dyslipidemia, type 2 diabetes mellitus,
      and hypertension. Effective interventions during human pregnancy and/or lactation
      are needed to improve both maternal and offspring health. This review addresses
      the relationship between adverse perinatal insults and its negative impact on
      offspring development and presents some maternal intervention studies such as
      diet modification, probiotic consumption, or maternal exercise, to prevent or
      alleviate the negative outcomes in both the mother and her child.

PMID- 29380311
TI  - Utility of Small Animal Models of Developmental Programming.
AB  - Any effective strategy to tackle the global obesity and rising noncommunicable
      disease epidemic requires an in-depth understanding of the mechanisms that
      underlie these conditions that manifest as a consequence of complex gene
      environment interactions. In this context, it is now well established that
      alterations in the early life environment, including suboptimal nutrition, can
      result in an increased risk for a range of metabolic, cardiovascular, and
      behavioral disorders in later life, a process preferentially termed developmental
      programming. To date, most of the mechanistic knowledge around the processes
      underpinning development programming has been derived from preclinical research
      performed mostly, but not exclusively, in laboratory mouse and rat strains. This
      review will cover the utility of small animal models in developmental
      programming, the limitations of such models, and potential future directions that
      are required to fully maximize information derived from preclinical models in
      order to effectively translate to clinical use.

PMID- 29380312
TI  - Generation of Maternal Obesity Models in Studies of Developmental Programming in
      Rodents.
AB  - Mother-child cohort studies have established that both pre-pregnancy body mass
      index (BMI) and gestational weight gain (GWG) are independently associated with
      cardio-metabolic risk factors in juvenile and adult offspring, including systolic
      and diastolic blood pressure. In rodent studies maternal obesity confers many
      facets of the metabolic syndrome including a persistent sympathy-excitatory
      hyperresponsiveness and hypertension acquired in the early stages of development.
      Insight from these animal models raises the possibility that early life exposure
      to the nutritional and hormonal environment of obesity in pregnancy in humans may
      lead to early onset of metabolic syndrome and/or essential hypertension. This
      chapter will address the development of rodent models of maternal overnutrition
      and obesity, which have proved invaluable in generating testable hypotheses for
      clinical translation and the development of intervention strategies to stem the
      swelling tide of obesity and its comorbidities predicted for future generations.

PMID- 29380313
TI  - Generation of the Maternal Low-Protein Rat Model for Studies of Metabolic
      Disorders.
AB  - Poor nutrition during pregnancy leads to an increased risk of metabolic disorders
      and other diseases in the offspring. This can be modelled in animals through
      manipulation of the maternal diet. One such model is the maternal low-protein rat
      which gives rise to offspring characterized by insulin resistance. This chapter
      gives a detailed protocol for generation of the maternal low-protein rat, which
      has been used in the study of several disorders including diabetes and
      psychiatric disorders.

PMID- 29380314
TI  - Investigation of Paternal Programming of Breast Cancer Risk in Female Offspring
      in Rodent Models.
AB  - Emerging experimental evidence show that fathers' experiences during
      preconception can influence their daughters' risk of developing breast cancer.
      Here we describe detailed protocols for investigation in rats and mice of
      paternally mediated breast cancer risk programming effects.

PMID- 29380315
TI  - Studies of Isolated Peripheral Blood Cells as a Model of Immune Dysfunction.
AB  - Peripheral blood mononuclear cells (PBMCs) have been used as a surrogate model of
      immune function in studies of multiple medical areas, such as metabolic diseases
      and immune dysfunction. This chapter describes a standardized technique for blood
      draw and preparation of PBMCs from whole blood using density gradient
      centrifugation, followed by cell culture. The main focus is on collection of the
      PBMC culture media and extraction of cellular proteins in order to provide the
      materials for biomarker studies.

PMID- 29380316
TI  - Studies of a Neuronal Cell Line as a Model of Psychiatric Disorders.
AB  - Mental disorders are generally characterized by a combination of abnormal
      thoughts, perceptions, emotions, behavior, and relationships with others.
      Although multiple risk factors, such as genetic and environmental factors and
      interaction of these factors, are suggested, the exact etiologies are not known.
      On the other hand, it has been strongly suggested that the dopaminergic system is
      impaired in a variety of mental disorders. In the described method, the SH-SY5Y
      neuroblastoma cell line is differentiated to neuronal cell which expresses NSE,
      neuronal marker, and dopamine transporter (DAT) by treatment with all-trans
      retinoic acid. SH-SY5Y cells allow investigating neuronal phenotypes of mental
      disorders as an in vitro model of these disorders.

PMID- 29380317
TI  - Assessment of Placental Transport Function in Studies of Disease Programming.
AB  - Environmental conditions during pregnancy affect fetal growth and development and
      program the offspring for poor future health. These effects may be mediated by
      the placenta, which develops to transfer nutrients from the mother to the fetus
      for growth. The ability to measure the unidirectional maternofetal transfer of
      non-metabolizable radio-analogues of glucose and amino acid by the placenta in
      vivo has thus been invaluable to our understanding of the regulation of fetal
      growth, particularly in small animal models. Herein, I describe the method by
      which in vivo placental transfer function can be quantified in the mouse, an
      animal model widely used in studies of in utero disease programming.

PMID- 29380318
TI  - Assessment of Fatty Liver in Models of Disease Programming.
AB  - Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of
      chronic liver disease worldwide and is present in a third of the general
      population and the majority of individuals with obesity and type 2 diabetes.
      Importantly, NAFLD can progress to severe nonalcoholic steatohepatitis (NASH),
      associated with liver failure and hepatocellular carcinoma. Recent research
      efforts have extensively focused on identifying factors contributing to the
      additional "hit" required to promote NALFD disease progression. The maternal
      diet, and in particular a high-fat diet (HFD), may be one such hit "priming" the
      development of severe fatty liver disease, a notion supported by the increasing
      incidence of NAFLD among children and adolescents in Westernized countries. In
      recent years, a plethora of key studies have used murine models of maternal
      obesity to identify fundamental mechanisms such as lipogenesis, mitochondrial
      function, inflammation, and fibrosis that may underlie the developmental priming
      of NAFLD. In this chapter, we will address key considerations for constructing
      experimental models and both conventional and advanced methods of quantifying
      NAFLD disease status.

PMID- 29380319
TI  - Capillary Blood Sampling from the Finger.
AB  - As the development of point of care testing devices improves, the uptake of
      capillary blood sampling from the fingertip across consumer groups and health
      professionals is increasing. The method promises to be a relatively safe and
      efficient method for monitoring patient health and obtaining research data.
      However, if not performed well, this simple technique can result in unreliable
      data and unsafe practices with a biological hazard. In this chapter, notes from
      the experiences of training undergraduate coursework and postgraduate research
      students in the method of capillary blood sampling from the fingertip are
      described to inform those considering the implementation of this method in
      teaching or research environments.

PMID- 29380320
TI  - Physical Activity Assessment in Clinical Studies of Substance Use Disorder.
AB  - The therapeutic effect of exercise in promoting mental health is well known, and
      there is a growing body of evidence for incorporating physical activity-based
      interventions in the management of substance use disorders (SUD). A particular
      challenge in this area is a lack of standardized testing protocols between
      studies and clear descriptive statistics on the capacity of the SUD patient to
      perform exercise. Therefore, an essential starting point for new studies that
      seek to incorporate exercise into usual care therapy for SUD is an appropriate
      suite of baseline fitness assessments that include measures of aerobic capacity
      as well as muscular strength and/or endurance. We present here the methods and
      notes of our recent experiences in implementing baseline fitness testing of a
      patient population undergoing in-patient treatment for SUD. The tests described
      here have been adapted from freely available standardized tests that were
      developed for implementation with the general population. It is hoped that these
      experiences aid in the development of patient-specific physical activity programs
      that assist in the management of SUD.

PMID- 29380321
TI  - Cardiopulmonary Exercise Testing.
AB  - Cardiopulmonary exercise testing (CPET) is an objective assessment of exercise
      capacity. It has become increasingly popular in clinical, research, and athletic
      performance settings. CPET allows for investigation of the cardiovascular,
      pulmonary, and skeletal muscle systems during exercise-induced stress. The main
      variable of maximal oxygen uptake (VO2max) reflects the gold standard measure of
      exercise capacity. This chapter will describe the method of performing a graded
      maximal CPET with the Vmax 229 Cardiopulmonary Exercise Testing Instrument and
      CardioSoft program.

PMID- 29380322
TI  - Cardiovascular Assessment in Human Research.
AB  - A number of noninvasive tests exist for assessing cardiovascular structure and
      function. This chapter describes protocols for flow-mediated dilation (FMD) of
      the brachial artery and pulse wave velocity (PWV) and pulse wave analysis (PWA)
      for measurement of arterial stiffness. The chapter also describes the different
      methodological approaches involved in applying these techniques for optimizing
      their validity, comparability, and potential uses as clinical and physiological
      research tools.

PMID- 29380323
TI  - Nutritional Programming Effects on the Immune System.
AB  - The relationship between patterns of early growth and age-associated diseases
      such as type 2 diabetes and cardiovascular disease is well established. There is
      also strong evidence from both human and animal studies that early environmental
      factors such as maternal nutrition may influence lifespan. Interestingly, more
      recent studies have demonstrated that nutritional programming in early life
      effects immunity, such that altered lifespan can also lead to programmed changes
      in immune function. Here we describe the use of immunohistology and flow
      cytometry techniques to study two key immune lymphoid organs: one that is
      involved in developing immune cells (thymus) and another which is the site of
      immune activation (spleen).

PMID- 29380324
TI  - Small RNA Sequencing: A Technique for miRNA Profiling.
AB  - Identifying microRNA (miRNA) signatures in animal tissues is an essential first
      step in studies assessing post-transcriptional regulation of gene expression in
      health or disease. Small RNA sequencing (sRNA-Seq) is a next-generation
      sequencing-based technology that is currently considered the most powerful and
      versatile tool for miRNA profiling. Here, we describe a sRNA-Seq protocol
      including RNA purification from mammalian tissues, library preparation, and raw
      data analysis.

PMID- 29380325
TI  - Pulse-Chase Biosynthetic Radiolabeling of Pancreatic Islets to Measure Beta Cell
      Function.
AB  - Pulse-chase radiolabeling of cells with radioactive amino acids is a common
      method for studying the biosynthesis of proteins. The labeled proteins can then
      be immunoprecipitated and analyzed by electrophoresis and gel imaging techniques.
      This chapter presents a protocol for the biosynthetic labeling and
      immunoprecipitation of pancreatic islet proteins which are known to be affected
      in disorders such as diabetes, obesity, and metabolic syndrome.

PMID- 29380326
TI  - Rapid and Easy Protocol for Quantification of Next-Generation Sequencing
      Libraries.
AB  - The emergence of next-generation sequencing (NGS) over the last 10 years has
      increased the efficiency of DNA sequencing in terms of speed, ease, and price.
      However, the exact quantification of a NGS library is crucial in order to obtain
      good data on sequencing platforms developed by the current market leader
      Illumina. Different approaches for DNA quantification are available currently and
      the most commonly used are based on analysis of the physical properties of the
      DNA through spectrophotometric or fluorometric methods. Although these methods
      are technically simple, they do not allow exact quantification as can be achieved
      using a real-time quantitative PCR (qPCR) approach. A qPCR protocol for DNA
      quantification with applications in NGS library preparation studies is presented
      here. This can be applied in various fields of study such as medical disorders
      resulting from nutritional programming disturbances.

PMID- 29380327
TI  - Telomere Length Analysis: A Tool for Dissecting Aging Mechanisms in Developmental
      Programming.
AB  - Accelerated cellular aging is known to play an important role in the etiology of
      phenotypes associated with developmental programming, such as cardiovascular
      disease and type 2 diabetes. Telomere length analysis is a powerful tool to
      quantify cellular aging. Here we describe a telomere length methodology, refined
      to quantify discrete telomere length fragments. We have shown this method to be
      more sensitive in detecting small changes in telomere length than the traditional
      average telomere length comparisons.

PMID- 29380328
TI  - Qualitative and Quantitative NMR Approaches in Blood Serum Lipidomics.
AB  - Nuclear magnetic resonance (NMR) spectroscopy in combination with chemometrics
      can be applied in the analysis of complex biological samples in many ways. For
      example, we can analyze lipids, elucidate their structures, determine their
      nutritional values, and determine their distribution in blood serum. As lipids
      are not soluble in water, they are transported in blood as lipid-rich self
      assembled particles, divided into different density assemblies from high- to very
      low-density lipoproteins (HDL to VLDL), or by combining with serum proteins, such
      as albumins (human serum albumins (HSA)). Therefore, serum lipids can be analyzed
      as they are using only a 1:1 (v/v) dilution with a buffer or deuterated water
      prior to analysis by applying 1H NMR or 1H NMR edited-by-diffusion techniques.
      Alternatively, lipids can be extracted from the serum using liquid partition
      equilibrium and then analyzed using liquid-state NMR techniques. Our chapter
      describes protocols that are used for extraction of blood serum lipids and their
      quantitative 1H NMR (1H qNMR) analysis in lipid extracts as well as 1H NMR edited
      by diffusion for direct blood serum lipid analysis.

PMID- 29380329
TI  - In Vivo Electrical Stimulation for the Assessment of Skeletal Muscle Contractile
      Function in Murine Models.
AB  - Skeletal muscle electrical stimulation is commonly used for clinical purposes,
      assisting recovery, preservation, or even improvement of muscle mass and function
      in healthy and pathological conditions. Additionally, it is a useful research
      tool for evaluation of skeletal muscle contractile function. It may be applied in
      vitro, using cell culture or isolated fibers/muscles, and in vivo, using human
      subjects or animal models (neuromuscular electrical stimulation - NMES). This
      chapter focuses on the electrical stimulation of the sciatic nerve as a research
      method for evaluation of the contractile properties of murine hind limb muscles.
      Variations of this protocol allow for the assessment of muscle force, fatigue
      resistance, contraction and relaxation times, and can be used as a model of
      contraction-induced muscle injury, reactive oxygen species production, and muscle
      adaptation to contractile activity.

PMID- 29380330
TI  - Experimental Model of Skeletal Muscle Laceration in Rats.
AB  - This is a modified experimental model previously developed in mouse to study
      skeletal muscle laceration in rats. All experimental procedures are performed
      during the light period, including anesthesia and surgery. The animals are
      randomly distributed into control and injured groups prior to the procedure. This
      experimental model can be used to investigate skeletal muscle laceration repair.

PMID- 29380331
TI  - Neuropsychiatric Sequelae of Early Nutritional Modifications: A Beginner's Guide
      to Behavioral Analysis.
AB  - Early parental nutritional interventions during prenatal development have been
      shown to result in neuropsychiatric sequelae in the adult offspring. In order to
      understand the impact of such nutritional interventions, the behavior of the
      animal has to be carefully analyzed. This chapter provides a step-by-step guide
      to conduct behavioral tests in adult mice for investigators without specific
      expertise or those without the equipment to carry out behavioral studies. We
      focus on tests tapping into the main behavioral abnormalities that correspond to
      mental illnesses. We describe the materials required and the detailed methods to
      conduct global assessment of parameters such as behavioral integrity and general
      well-being, psychomotor activity, social behavior, repetitive behavior, anxiety
      like behavior, depression-like behavior, short-term spatial working memory, and
      spatial reference memory.

PMID- 29380332
TI  - Hyperlocomotion Test for Assessing Behavioral Disorders.
AB  - Under- or overfeeding during pregnancy can lead to behavioral deficits in the
      offspring in later life. Here, we present a protocol for setting up and carrying
      out the hyperlocomotion test for assessing behavioral symptoms such as psychosis
      or mania. As an example, we use the acute rat phencyclidine-injection model which
      exhibits hyperlocomotion and stereotypic behaviors, resembling the positive
      symptoms of schizophrenia.

PMID- 29380333
TI  - 2D-DIGE Analysis of Eye Lens Proteins as a Measure of Cataract Formation.
AB  - This chapter describes the basics of two-dimensional difference gel
      electrophoresis (2D-DIGE) for multiplex analysis of two distinct proteomes. The
      example given describes the analysis of male and female rat lens soluble proteins
      labeled with fluorescent Cy3 and Cy5 dyes in comparison to a pooled standard
      labeled with Cy2. After labeling the proteomes are mixed together and
      electrophoresed on the same 2D gels. Scanning the gels at wavelengths specific
      for each dye allows direct overlay the two different proteomes. Differences in
      abundance of specific protein spots can be determined through comparison to the
      pooled standard.

PMID- 29380334
TI  - Mass Spectrometry Profiling of Pituitary Glands.
AB  - Many chronic diseases are associated with hypothalamic-pituitary-adrenal axis
      dysfunction. Therefore, proteomic profiling of the pituitary gland has potential
      to uncover new information on the underlying pathways affected in these
      conditions. This could lead to identification of new biomarkers or drug targets
      for development of novel therapeutics. Here we present a protocol for preparation
      of pituitary protein extracts and analysis of the major hormones and accessory
      proteins using liquid chromatography tandem mass spectrometry (LC-MS/MS). The
      same methods can be applied in the study of other tissues of the diffuse
      neuroendocrine system.

PMID- 29380335
TI  - Multiplex Immunoassay Profiling of Hormones Involved in Metabolic Regulation.
AB  - Multiplex immunoassays are used for rapid profiling of biomarker proteins and
      small molecules in biological fluids. The advantages over single immunoassays
      include lower sample consumption, cost, and labor. This chapter details a
      protocol to develop a 5-plex assay for glucagon-like peptide 1, growth hormone,
      insulin, leptin, and thyroid-stimulating hormone on the Luminex(r) platform. The
      results of the analysis of insulin in normal control subjects are given due to
      the important role of this hormone in nutritional programming diseases.

PMID- 29380336
TI  - Time-Resolved Fluorescence Assays for Quantification of Insulin Precursors in
      Plasma and Serum.
AB  - In metabolic diseases such as obesity and type 2 diabetes mellitus, the
      conversion of proinsulin to mature insulin can be impaired. This could mean that
      insulin molecules with lower activity toward the insulin receptor can be released
      under conditions of high metabolic demand, resulting in an inadequate
      glucoregulatory response. The chapter describes a fluorescent monoclonal antibody
      based protocol for measurement of human proinsulin and the proinsulin conversion
      intermediates (split proinsulins). An example assay is presented using serum from
      non-diabetic, normal body mass index individuals.

PMID- 29380337
TI  - Identification of Neural Stem Cell Biomarkers by Isobaric Tagging for Relative
      and Absolute Quantitation (iTRAQ) Mass Spectrometry.
AB  - This chapter describes a proteomic analysis of neural progenitor cells using
      isobaric tagging for relative and absolute quantitation (iTRAQ) mass
      spectrometry. A detailed procedure is described for the isolation, proliferation,
      and differentiation of these cells, including a comparative iTRAQ mass
      spectrometry analysis of the precursor and differentiated states. In total, there
      were changes in the levels of 55 proteins, many of which are not resolved easily
      by other proteomic methods. Therefore, this method should be useful for the
      identification of important regulatory molecules in the study of other precursor
      cells involved in neuronal or metabolic regulation in nutritional programming
      diseases.

PMID- 29380338
TI  - Lab-on-a-Chip Device for Rapid Measurement of Vitamin D Levels.
AB  - Lab-on-a-chip assays allow rapid analysis of one or more molecular analytes on an
      automated user-friendly platform. Here we describe a fully automated assay and
      readout for measurement of vitamin D levels in less than 15 min using the
      Fraunhofer in vitro diagnostics platform. Vitamin D (25-hydroxyvitamin D3
      [25(OH)D3]) dilution series in buffer were successfully tested down to 2 ng/mL.
      This could be applied in the future as an inexpensive point-of-care analysis for
      patients suffering from a variety of conditions marked by vitamin D deficiencies.

PMID- 29380339
TI  - Kidney Smartphone Diagnostics.
AB  - Here we present a method for a mobile point-of-care (POC) testing of urinary
      albumin concentration, a biomarker of kidney damage and cardiovascular disease.
      The self-testing strips are meant to be interpreted by means of a smartphone
      application. The limits of detection range from 0.15 to 0.30 g/L urinary albumin,
      though results below 0.10 g/L are presented in a quantitative manner and
      estimates larger than this threshold are shown as categorical variables in a
      qualitative manner for increasing urinary albumin concentrations. Calibrated once
      under standard conditions, the app enables the user to capture problem samples
      and calculate the corresponding concentration. Negative and positive findings
      must be interpreted, taking into account the inherent limitations of the method,
      and professional health advice must be requested for diagnostic considerations.
      Acknowledgment of the association between early life nutrition and long-term
      renal health and the adoption of preventive strategies targeting high-risk groups
      is key for the reduction of the burden of chronic kidney disease on a global
      scale.

PMID- 29380340
TI  - A User-Friendly App for Blood Coagulation Disorders.
AB  - There is a strong association between a suboptimal maternal environment and
      increased risk of developing age-associated diseases such as type 2 diabetes,
      obesity, and cardiovascular disease in the offspring. Blood clotting time may be
      altered in all of these conditions, and it is also an important factor that
      requires monitoring in postoperative and cardiovascular disorder patients who are
      on coagulant medications. This chapter describes patient self-management of blood
      coagulation activity using a test strip device and the Coagu app. The app can
      also be used as a reminder of treatment times and for monitoring the effects of
      treatment over time.

PMID- 29380341
TI  - Hormonal Smartphone Diagnostics.
AB  - Mobile point-of-care diagnostics are paramount for the provision of healthcare.
      Hormonal diagnostics are powerful tools to monitor timely changes in human
      physiology. Hormone concentrations in serum directly correlate with urine
      excretions with minor time delays. Therefore, rapid tests for hormones in urine
      have been widely used for decades as means of early diagnostics, particularly in
      lateral flow immunoassay formats. However, the challenge of reading and
      interpreting these binary tests remains. Here we present a method for utilizing
      mobile technologies to quantitatively read and interpret hormonal test strips.
      The method demonstrates the detection of a urinary by-product of progesterone,
      pregnanediol glucuronide (PdG), and its relation to ovulation and the fertility
      cycle.

PMID- 29380342
TI  - Risk-Predicting Model for Incident of Essential Hypertension Based on
      Environmental and Genetic Factors with Support Vector Machine.
AB  - Essential hypertension (EH) has become a major chronic disease around the world.
      To build a risk-predicting model for EH can help to interpose people's lifestyle
      and dietary habit to decrease the risk of getting EH. In this study, we
      constructed a EH risk-predicting model considering both environmental and genetic
      factors with support vector machine (SVM). The data were collected through
      Epidemiological investigation questionnaire from Beijing Chinese Han population.
      After data cleaning, we finally selected 9 environmental factors and 12 genetic
      factors to construct the predicting model based on 1200 samples, including 559
      essential hypertension patients and 641 controls. Using radial basis kernel
      function, predictive accuracy via SVM with function with only environmental
      factor and only genetic factor were 72.8 and 54.4%, respectively; after
      considering both environmental and genetic factor the accuracy improved to 76.3%.
      Using the model via SVM with Laplacian function, the accuracy with only
      environmental factor and only genetic factor were 76.9 and 57.7%, respectively;
      after combining environmental and genetic factor, the accuracy improved to 80.1%.
      The predictive accuracy of SVM model constructed based on Laplacian function was
      higher than radial basis kernel function, as well as sensitivity and specificity,
      which were 63.3 and 86.7%, respectively. In conclusion, the model based on SVM
      with Laplacian kernel function had better performance in predicting risk of
      hypertension. And SVM model considering both environmental and genetic factors
      had better performance than the model with environmental or genetic factors only.

PMID- 29380343
TI  - Prenatal diagnosis and socioeconomic status in the non-invasive prenatal testing
      era: A population-based study.
AB  - BACKGROUND: Advances in technology can bring great benefits to human health, but
      their implementation may be influenced by socioeconomic factors, particularly in
      the field of prenatal screening for Down syndrome. AIM: To analyse screening test
      indications for, and diagnostic yield of, invasive prenatal diagnostic testing
      (PNDx) according to socioeconomic status. METHODS: Retrospective analysis of
      population-based data on PNDx and karyotype results for 2014-2015 in the
      Australian state of Victoria. Women having PNDx < 25 weeks due to combined first
      trimester screening (CFTS), second trimester serum screening (STSS), or
      noninvasive prenatal testing (NIPT) results were included. PNDx data were
      analysed by indication and maternal Index of Relative Socio-economic Advantage
      and Disadvantage (IRSAD), the latter determined by postcode. RESULTS: There were
      145 206 births in 2014-2015; 1906 women underwent PNDx for the indication of CFTS
      (70.1%), NIPT (17.8%) or STSS (12.0%). Covariates positively associated with NIPT
      indicated PNDx, compared with CFTS-indicated testing, were residence in a region
      of socioeconomic advantage, metropolitan status and maternal age. Women from the
      most advantaged regions had higher adjusted odds ratios (aOR) of NIPT-indicated
      testing compared with women from disadvantaged regions (aOR 5.72, 95% CI: 2.95
      11.09). The diagnostic yield of PNDx increased with socioeconomic region, from
      14% in the lowest IRSAD quintile to 31.2% in the highest (P < 0.0001).
      CONCLUSION: Population-based data reveal significant disparities in screening
      indications for PNDx and hence, in diagnostic yield, according to socioeconomic
      region. This finding may have ethical and policy implications for prenatal
      screening in Australia.

PMID- 29380344
TI  - Digest: Sexual selection and conflict in a novel environment.

PMID- 29380345
TI  - An evaluation of routine antenatal depression screening and psychosocial
      assessment in a regional private maternity setting in Australia.
AB  - BACKGROUND: There is limited information relating to routine depression screening
      and psychosocial assessment programs in private maternity settings in Australia.
      AIMS: To describe the psychosocial profile of a sample of private maternity
      patients who participated in a depression screening and psychosocial risk
      assessment program as part of routine antenatal care, and to explore women's
      experience of receiving this component of pregnancy care. MATERIALS AND METHODS:
      We conducted a retrospective medical records audit of 455 consecutive women
      having a routine psychosocial assessment and referral. Assessment was undertaken
      using the Edinburgh Postnatal Depression Scale (EPDS) and the Antenatal Risk
      Questionnaire (ANRQ) for psychosocial risk; 101 women completed a feedback survey
      about their experience of receiving routine psychosocial care. RESULTS: Of the
      87.7% of women who completed both EPDS and ANRQ, 4.3% scored 13 or more on the
      EPDS. On the ANRQ, 25.3% of women endorsed one risk factor, 11.6% two risk
      factors and 10.5% three or more risk factors. Elevated EPDS scores were
      associated with major stresses in the last 12 months, high trait anxiety and
      significant past mental health issue/s. Acceptability of depression screening and
      psychosocial risk assessment was high. CONCLUSIONS: This study highlights the
      need for, and acceptability of, depression and psychosocial assessment in the
      private maternity sector. These findings are particularly timely given the
      provision of new Medicare Benefits Scheme items for obstetricians to undertake
      psychosocial assessment (both antenatally and postnally) in line with recommended
      clinical best practice.

PMID- 29380346
TI  - The Education of Prescribers for Safe and Effective Use of Medications.
AB  - The transformation of medical education, with the disappearance of sequential
      lectures in pharmacology, clinical pharmacology, and therapeutics, has left gaps
      in skills needed for new physicians and other prescribers to safely incorporate
      medications into clinical practice. Brinkman et al. conducted a Delphi study of
      European Union (EU) medical school educators and practitioners to identify core
      competencies needed to prescribe medications. Their findings offer directions for
      learned societies, such as ASCPT, to enhance pharmacology education and practice.

PMID- 29380347
TI  - Digest: The Red Queen hypothesis demonstrated by the Daphnia-Caullerya host
      parasite system?.

PMID- 29380348
TI  - Nickel hypersensitivity following closure of atrial septal defect: A case report
      and review of the literature.
AB  - We present an unusual case where symptoms of headache and chest pain persisted
      for 3 years following the implantation of a septal occluder device for an atrial
      septal defect despite endothelialisation of the device. The patient was found to
      have nickel hypersensitivity on patch testing. Following the removal of the
      device the patient had complete resolution of headaches and chest pain up to 10
      months post-explantation.

PMID- 29380349
TI  - Acne and hidradenitis suppurativa.
AB  - Acne and hidradenitis suppurativa (HS) both centre on hair follicles. They often
      occur together as part of the acne tetrad, but are found in distinct
      localizations. Acne is primarily defined by the presence of comedones and
      inflammatory lesions. However, in HS the intertriginous localization and
      chronicity play equally important roles for the diagnosis to the inflammatory
      lesions. Genetics, bacteria, environmental factors and innate inflammation have
      all been found to play a role in acne and/or HS. Surprisingly, there is little
      overlap between the findings so far. The genetics of acne and HS are distinct,
      bacteria have not been shown convincingly to play a role in HS, and the important
      risk factors obesity and smoking in HS cannot be easily translated to acne. The
      one driving factor central to both diseases is innate inflammation, most
      strikingly involving interleukin-1. Hence the interleukin-1 family, as already
      shown in autoinflammatory conditions associated with acne, could represent
      attractive treatment targets.

PMID- 29380350
TI  - Retrospective study of rapamycin or rapalog 0.1% cream for facial angiofibromas
      in tuberous sclerosis complex: evaluation of treatment effectiveness and cost.

PMID- 29380351
TI  - Complex coevolution of wing, tail, and vocal sounds of courting male bee
      hummingbirds.
AB  - Phenotypic characters with a complex physical basis may have a correspondingly
      complex evolutionary history. Males in the "bee" hummingbird clade court females
      with sound from tail-feathers, which flutter during display dives. On a phylogeny
      of 35 species, flutter sound frequency evolves as a gradual, continuous character
      on most branches. But on at least six internal branches fall two types of major,
      saltational changes: mode of flutter changes, or the feather that is the sound
      source changes, causing frequency to jump from one discrete value to another. In
      addition to their tail "instruments," males also court females with sound from
      their syrinx and wing feathers, and may transfer or switch instruments over
      evolutionary time. In support of this, we found a negative phylogenetic
      correlation between presence of wing trills and singing. We hypothesize this
      transference occurs because wing trills and vocal songs serve similar functions
      and are thus redundant. There are also three independent origins of self
      convergence of multiple signals, in which the same species produces both a vocal
      (sung) frequency sweep, and a highly similar nonvocal sound. Moreover, production
      of vocal, learned song has been lost repeatedly. Male bee hummingbirds court
      females with a diverse, coevolving array of acoustic traits.

PMID- 29380352
TI  - Regulation of glucose-stimulated insulin secretion by ATPase Inhibitory Factor 1
      (IF1).
AB  - ATPase Inhibitory factor 1 (IF1) is an endogenous regulator of mitochondrial ATP
      synthase, which is involved in cellular metabolism. Although great progress has
      been made, biological roles of IF1 and molecular mechanisms of its action are
      still to be elucidated. Here, we show that IF1 is present in pancreatic beta
      cells, bound to the ATP synthase also under normal physiological conditions. IF1
      silencing in model pancreatic beta-cells (INS-1E) increases insulin secretion
      over a range of glucose concentrations. The left-shifted dose-response curve
      reveals excessive insulin secretion even under low glucose, corresponding to
      fasting conditions. A parallel increase in cellular respiration and ATP levels is
      observed. To conclude, our results indicate that IF1 is a negative regulator of
      insulin secretion involved in pancreatic beta-cell glucose sensing.

PMID- 29380353
TI  - Regenerative Solutions for Inherited Diseases.
AB  - It is clear that regenerative medicine therapies will dominate the future
      landscape, particularly for genetic disorders and other diseases that have been
      proven intractable with current therapies. As we explore unique combinations of
      rapidly emerging fields-from computational biology to genome editing to molecular
      therapeutics-the past goal of ameliorating symptoms of disease is rapidly giving
      way to the goal of restoring a patient to health and normal function.

PMID- 29380354
TI  - Digest: Shape-shifting in Solanaceae flowers: The influence of pollinators.

PMID- 29380355
TI  - Can the Use of Novel Digital Devices Improve the Productivity of Drug
      Development?
AB  - Pharmaceutical companies have been forever challenged with both rising
      development costs and the need to find novel ways to differentiate the candidate
      drugs. Recent advances in digital health (DH) technology, including wearables, in
      home clinical devices, and sensors, have enabled a growing array of available
      data endpoints, making these devices an invaluable tool in clinical programs. The
      below analysis focuses on advantages and hurdles in implementation of selected DH
      technologies in drug development.

PMID- 29380356
TI  - Association between visual inspection of the cervix with acetic acid examination
      and high-risk human papillomavirus infection, Chlamydia trachomatis, Neisseria
      gonorrhoeae and Trichomonas vaginalis in Papua New Guinea.
AB  - BACKGROUND: Papua New Guinea (PNG) has among the highest estimated burdens of
      cervical cancer globally but currently has no national cervical screening
      program. Visual inspection of the cervix with acetic acid (VIA) is a low-cost
      screening strategy endorsed by the World Health Organization that has been
      adopted in many low-resource settings but not previously evaluated in PNG. AIM:
      To evaluate the association between VIA examination findings and high-risk HPV
      (hrHPV) infection; and the impact of concomitant genital Chlamydia trachomatis,
      Neisseria gonorrhoeae and Trichomonas vaginalis on the interpretation of VIA
      findings. METHODS: A prospective clinical cohort study among women aged 30-59
      years attending Well Woman Clinics in PNG. Main outcome measures were VIA
      examination findings and laboratory-confirmed hrHPV, C. trachomatis, N.
      gonorrhoeae and T. vaginalis. RESULTS: A total of 614 women were enrolled, of
      whom 87.5% (537/614) underwent VIA, and 12.5% (77/614) did not due to pre
      existing cervicitis or inability to visualise the transformation zone. Among the
      537 women who underwent VIA, 21.6% were VIA positive, 63.7% VIA negative, and
      14.7% had indeterminate findings. The prevalence of hrHPV infection (n = 614) was
      14.7%; C. trachomatis, 7.5%; N. gonorrhoeae, 8.0%; and T. vaginalis, 15.0%. VIA
      positive women were more likely to have HPV16 (odds ratio: 5.0; 95%CI: 1.6-15.6;
      P = 0.006) but there was no association between HPV18/45, all hrHPV types
      (combined), C. trachomatis, N. gonorrhoeae or T. vaginalis. CONCLUSIONS: VIA
      positivity was associated with HPV16, but not with other hrHPV infections, nor
      with genital C. trachomatis, N. gonorrhoeae or T. vaginalis in this setting.

PMID- 29380357
TI  - The association between ragged or incomplete membranes and postpartum
      haemorrhage: A retrospective cohort study.
AB  - BACKGROUND: The association between an incomplete placenta and postpartum
      haemorrhage (PPH) is well documented; however, the significance of ragged or
      incomplete membranes has not been explored as an independent risk factor for PPH.
      AIMS: To explore the association between the completeness of the amniotic and
      chorionic membranes and the risk of PPH, independent to placental status.
      MATERIALS AND METHODS: 37 176 birth records were retrospectively extracted from
      the period 1 July, 2008 to 30 June, 2016 from the databases of two public
      hospitals in Melbourne, Australia. Following application of specific exclusion
      and inclusion criteria, including non-complete placentas, 5718 records were
      available for analysis. These records were grouped based on membrane status
      (complete, ragged or incomplete) and outcome (PPH or no PPH). RESULTS: Primary
      PPH rates were 14.8% in women with complete membranes, 20.2% in women with ragged
      membranes and 25.8% in women with incomplete membranes. Following statistical
      adjustment, the risk ratios for PPH were 1.32 (95% CI: 1.15-1.50) and 1.70 (95%
      CI: 1.41-2.04) in women with ragged and incomplete membranes, respectively.
      CONCLUSIONS: Both ragged and incomplete membranes were found to be independent
      risk factors for primary PPH. This previously un-discussed association has the
      potential to influence clinical practice changes, particularly with regard to the
      ongoing clinical relevance and use of the terms 'ragged' and 'incomplete'
      membranes.

PMID- 29380358
TI  - Rapid exacerbation of malignant melanoma during short-term discontinuation of
      vemurafenib.

PMID- 29380359
TI  - Autologous stem cell transplant and combination immunotherapy of rituximab and
      interferon-alpha induces prolonged clinical and molecular remissions in patients
      with follicular lymphoma.

PMID- 29380361
TI  - Evolution of mutualism from parasitism in experimental virus populations.
AB  - While theory suggests conditions under which mutualism may evolve from
      parasitism, few studies have observed this transition empirically. Previously, we
      evolved Escherichia coli and the filamentous bacteriophage M13 in 96-well
      microplates, an environment in which the ancestral phage increased the growth
      rate and yield of the ancestral bacteria. In the majority of populations,
      mutualism was maintained or even enhanced between phages and coevolving bacteria;
      however, these same phages evolved traits that harmed the ancestral E. coli
      genotype. Here, we set out to determine if mutualism could evolve from this new
      parasitic interaction. To do so, we chose six evolved phage populations from the
      original experiment and used them to establish new infections of the ancestral
      bacteria. After 20 passages, mutualism evolved in almost all replicates, with the
      remainder growing commensally. Many phage populations also evolved to benefit
      both their local, evolving bacteria and the ancestral bacteria, though these
      phages were less beneficial to their co-occurring hosts than phages that harm the
      ancestral bacteria. These results demonstrate the rapid recovery of mutualism
      from parasitism, and we discuss how our findings relate to the evolution of
      phages that enhance the virulence of bacterial pathogens.

PMID- 29380360
TI  - Dorsomedial Prefrontal Activity to Sadness Predicts Later Emotion Suppression and
      Depression Severity in Adolescent Girls.
AB  - The present study used cross-lagged panel analyses to test longitudinal
      associations among emotion regulation, prefrontal cortex (PFC) function, and
      depression severity in adolescent girls. The ventromedial and dorsomedial PFC
      (vmPFC and dmPFC) were regions of interest given their roles in depression
      pathophysiology, self-referential processing, and emotion regulation. At ages 16
      and 17, seventy-eight girls completed a neuroimaging scan to assess changes in
      vmPFC and dmPFC activation to sad faces, and measures of depressive symptom
      severity and emotion regulation. The 1-year cross-lagged effects of dmPFC
      activity at age 16 on expressive suppression at age 17 and depressive
      symptomatology at age 17 were significant, demonstrating a predictive relation
      between dmPFC activity and both suppression and depressive severity.

PMID- 29380362
TI  - Post-transplant lymphoproliferative disease with features of cutaneous natural
      killer/T-cell lymphoma.

PMID- 29380363
TI  - Invasion history alters the behavioural consequences of immune system activation
      in cane toads.
AB  - Acute activation of the immune system often initiates a suite of behavioural
      changes. These "sickness behaviours"-involving lethargy and decreased activity
      may be particularly costly on invasion fronts, where evolutionary pressures on
      dispersal favour individuals that move large distances. We used a combination of
      field and laboratory studies to compare sickness behaviours of cane toads from
      populations differing in invasion history. To do this we stimulated immune system
      activation by injecting lipopolysaccharide (LPS) to mimic bacterial infection. We
      predicted that LPS would result in less severe sickness behaviour in toads from
      range-edge populations because they had undergone selection for rapid and
      sustained dispersal (activities in conflict with lethargy and decreased
      activity). Contrary to our prediction, LPS injection caused a greater reduction
      in dispersal-relevant traits in invasion-front individuals than in conspecifics
      from the range-core. Our data suggest that the rapid invasion of cane toads
      through tropical Australia has seen an evolutionary shift in the magnitude of
      sickness behaviour elicited by pathogen infection. The increased sickness
      behaviour among range-edge toads suggests a shift away from pathogen tolerance
      (seen in range-core populations) towards resistance to pathogen attack. But as a
      consequence, when pathogens do become successfully established, toads from
      invasion-front populations may have less capacity to tolerate their ill-effects.

PMID- 29380364
TI  - Density regulation in Northeast Atlantic fish populations: Density dependence is
      stronger in recruitment than in somatic growth.
AB  - Population regulation is a central concept in ecology, yet in many cases its
      presence and the underlying mechanisms are difficult to demonstrate. The current
      paradigm maintains that marine fish populations are predominantly regulated by
      density-dependent recruitment. While it is known that density-dependent somatic
      growth can be present too, its general importance remains unknown and most
      practical applications neglect it. This study aimed to close this gap by for the
      first time quantifying and comparing density dependence in growth and recruitment
      over a large set of fish populations. We fitted density-dependent models to time
      series data on population size, recruitment and age-specific weight from
      commercially exploited fish populations in the Northeast Atlantic Ocean and the
      Baltic Sea. Data were standardized to enable a direct comparison within and among
      populations, and estimated parameters were used to quantify the impact of density
      regulation on population biomass. Statistically significant density dependence in
      recruitment was detected in a large proportion of populations (70%), whereas for
      density dependence in somatic growth the prevalence of density dependence
      depended heavily on the method (26% and 69%). Despite age-dependent variability,
      the density dependence in recruitment was consistently stronger among age groups
      and between alternative approaches that use weight-at-age or weight increments to
      assess growth. Estimates of density-dependent reduction in biomass underlined
      these results: 97% of populations with statistically significant parameters for
      growth and recruitment showed a larger impact of density-dependent recruitment on
      population biomass. The results reaffirm the importance of density-dependent
      recruitment in marine fishes, yet they also show that density dependence in
      somatic growth is not uncommon. Furthermore, the results are important from an
      applied perspective because density dependence in somatic growth affects
      productivity and catch composition, and therefore the benefits of maintaining
      fish populations at specific densities.

PMID- 29380365
TI  - Fat feeding facilitates hot bodies, but is resistance futile?

PMID- 29380366
TI  - Biodegradable nanoparticles as theranostics of ovarian cancer: an overview.
AB  - OBJECTIVES: Above 10 million people are suffering from cancers every year. As per
      American Cancer Society, more than 22 440 new cases and 14 080 deaths were
      reported from ovarian cancer yearly worldwide. This review explores the current
      status, challenges and future perspectives of tumour-targeted theranostic
      nanoparticles (NPs). KEY FINDINGS: Most of the ovarian malignancy cases are
      uncovered after the disease is in a difficult state due to poor screening
      techniques and non-specific symptoms. In this manner, forceful and fruitful
      treatment is required that will indicate insignificant lethal impacts to solid
      tissue. In the current research, stealth biodegradable NPs are produced as
      vehicles for imaging and treatment of ovarian cancer as the controlled and
      targeted delivery of chemotherapeutic as well as imaging agents. To enhance the
      dependability of the colloidal suspension as well as to increase their
      circulation lifetime, NPs are introduced by incorporating the functional
      poly(ethylene glycol) on their surface, which also provides a site to conjugation
      of focusing on agents to ovarian tissue. SUMMARY: Biodegradable theranostic NPs
      can be fabricated and surface engineered without any alteration in drug-loading
      capacity, safety and efficacy. These NPs have shown promising results in imaging
      as well as treatment of ovarian cancer.

PMID- 29380367
TI  - MicroRNA-421 suppresses the apoptosis and autophagy of hippocampal neurons in
      epilepsy mice model by inhibition of the TLR/MYD88 pathway.
AB  - Epilepsy is a group of neurological disorders characterized by epileptic
      seizures. In this study, we aim to explore the role of microRNA-421 (miR-421) in
      hippocampal neurons of epilepsy mice via the TLR/MYD88 pathway. Forty mice were
      randomly served as the normal and model (established as epilepsy model) groups.
      Hippocampal neurons were assigned into seven groups with different transfections.
      The RT-qPCR and western blotting were conducted to examine the expression of miR
      421 TLR2, TLR4, MYD88, Bax, Bcl-2, p53, Beclin-1, and LC3II/LC3I. Cell
      proliferation and apoptosis were detected by MTT and flow cytometry.MYD88 is a
      target gene of miR-421. Model mice showed elevated expression of TLR2, TLR4,
      MYD88, Bax, p53, Beclin-1, and LC3II/LC3I but reduced expression of miR-421 and
      Bcl-2. In vitro experiments reveals that overexpression of miR-421 inhibited the
      TLR/MYD88 pathway. Besides, overexpressed miR-421 declined cell apoptosis but
      increased cell proliferation. It reveals that miR-421 targeting MYD88 could
      inhibit the apoptosis and autophagy of hippocampal neurons in epilepsy mice by
      down-regulating the TLR/MYD88 pathway.

PMID- 29380368
TI  - Tributyltin induces distinct effects on cortical and trabecular bone in female
      C57Bl/6J mice.
AB  - The retinoid X receptors (RXR), peroxisome proliferator activated receptor gamma
      (PPARgamma), and liver X receptors (LXR) all have been shown to regulate bone
      homeostasis. Tributyltin (TBT) is an environmental contaminant that is a dual
      RXRalpha/beta and PPARgamma agonist. TBT induces RXR, PPARgamma, and LXR-mediated
      gene transcription and suppresses osteoblast differentiation in vitro. Bone
      marrow multipotent mesenchymal stromal cells derived from female C57BL/6J mice
      were more sensitive to suppression of osteogenesis by TBT than those derived from
      male mice. In vivo, oral gavage of 12 week old female, C57Bl/6J mice with 10
      mg/kg TBT for 10 weeks resulted in femurs with a smaller cross-sectional area and
      thinner cortex. Surprisingly, TBT induced significant increases in trabecular
      thickness, number, and bone volume fraction. TBT treatment did not change the
      Rankl:Opg RNA ratio in whole bone, and histological analyses showed that
      osteoclasts in the trabecular space were minimally reduced. In contrast,
      expression of cardiotrophin-1, an osteoblastogenic cytokine secreted by
      osteoclasts, increased. In primary bone marrow macrophage cultures, TBT
      marginally inhibited the number of osteoclasts that differentiated, in spite of
      significantly suppressing expression of osteoclast markers Nfatc1, Acp5, and Ctsk
      and resorptive activity. TBT induced expression of RXR- and LXR-dependent genes
      in whole bone and in vitro osteoclast cultures. However, only an RXR antagonist,
      but not an LXR antagonist, significantly inhibited TBTs ability to suppress
      osteoclast differentiation. These results suggest that TBT has distinct effects
      on cortical versus trabecular bone, likely resulting from independent effects on
      osteoblast and osteoclast differentiation that are mediated through RXR.

PMID- 29380369
TI  - Development, current applications and future roles of biorelevant two-stage in
      vitro testing in drug development.
AB  - OBJECTIVES: Various types of two stage in vitro testing have been used in a
      number of experimental settings. In addition to its application in quality
      control and for regulatory purposes, two-stage in vitro testing has also been
      shown to be a valuable technique to evaluate the supersaturation and
      precipitation behavior of poorly soluble drugs during drug development. KEY
      FINDINGS: The so-called 'transfer model', which is an example of two-stage
      testing, has provided valuable information about the in vivo performance of
      poorly soluble, weakly basic drugs by simulating the gastrointestinal drug
      transit from the stomach into the small intestine with a peristaltic pump. The
      evolution of the transfer model has resulted in various modifications of the
      experimental model set-up. Concomitantly, various research groups have developed
      simplified approaches to two-stage testing to investigate the supersaturation and
      precipitation behavior of weakly basic drugs without the necessity of using a
      transfer pump. SUMMARY: Given the diversity among the various two-stage test
      methods available today, a more harmonized approach needs to be taken to optimize
      the use of two stage testing at different stages of drug development.

PMID- 29380371
TI  - Novel application of internal obturator and semitendinosus muscle flaps for
      rectal wall repair or reinforcement.
AB  - Internal obturator and/or semitendinosus muscle flaps were used to reinforce
      primary appositional rectal wall repair in three dogs and one cat in this case
      series. All three dogs incurred rectal wall compromise during surgical excision
      of anal sac tumours. The cat sustained bite wounds to the perianal region
      resulting in abscessation and a rectal tear. Our results indicate that
      application of an internal obturator and/or semitendinosus muscle flap can reduce
      the risk of rectal wall dehiscence after primary repair, and consequently the
      risk of pararectal abscess or rectocutaneous fistula formation.

PMID- 29380370
TI  - Endothelial immune activation programmes cell-fate decisions and angiogenesis by
      inducing angiogenesis regulator DLL4 through TLR4-ERK-FOXC2 signalling.
AB  - KEY POINTS: The mechanisms by which bacteria alter endothelial cell phenotypes
      and programme inflammatory angiogenesis remain unclear. In lung endothelial
      cells, we demonstrate that toll-like receptor 4 (TLR4) signalling induces
      activation of forkhead box protein C2 (FOXC2), a transcriptional factor
      implicated in lymphangiogenesis and endothelial specification, in an
      extracellular signal-regulated kinase (ERK)-dependent manner. TLR4-ERK-FOXC2
      signalling regulates expression of the Notch ligand DLL4 and signals inflammatory
      angiogenesis in vivo and in vitro. Our work reveals a novel link between
      endothelial immune signalling (TLR pathway) and a vascular transcription factor,
      FOXC2, that regulates embryonic vascular development. This mechanism is likely to
      be relevant to pathological angiogenesis complicating inflammatory diseases in
      humans. ABSTRACT: Endothelial cells (ECs) mediate a specific and robust immune
      response to bacteria in sepsis through the activation of toll-like receptor (TLR)
      signalling. The mechanisms by which bacterial ligands released during sepsis
      programme EC specification and altered angiogenesis remain unclear. We postulated
      that the forkhead box protein C2 (FOXC2) transcriptional factor directs EC cell
      fate decisions and angiogenesis during TLR signalling. In human lung ECs,
      lipopolysaccharide (LPS) induced ERK phosphorylation, FOXC2, and delta-like 4
      (DLL4, the master regulator of sprouting angiogenesis expression) in a TLR4
      dependent manner. LPS-mediated ERK phosphorylation resulted in FOXC2-ERK protein
      ligation, ERK-dependent FOXC2 serine and threonine phosphorylation, and
      subsequent activation of DLL4 gene expression. Chemical inhibition of ERK or ERK
      2 dominant negative transfection disrupted LPS-mediated FOXC2 phosphorylation and
      transcriptional activation of FOXC2. FOXC2-siRNA or ERK-inhibition attenuated LPS
      induced DLL4 expression and angiogenic sprouting in vitro. In vivo,
      intraperitoneal LPS induced ERK and FOXC2 phosphorylation, FOXC2 binding to DLL4
      promoter, and FOXC2/DLL4 expression in the lung. ERK-inhibition suppressed LPS
      induced FOXC2 phosphorylation, FOXC2-DLL4 promoter binding, and induction of
      FOXC2 and DLL4 in mouse lung ECs. LPS induced aberrant retinal angiogenesis and
      DLL4 expression in neonatal mice, which was attenuated with ERK inhibition.
      FOXC2+/- mice treated with LPS showed a mitigated increase in FOXC2 and DLL4
      compared to FOXC2+/+ mice. These data reveal a new mechanism (TLR4-ERK-FOXC2
      DLL4) by which sepsis-induced EC TLR signalling programmes EC specification and
      altered angiogenesis.

PMID- 29380372
TI  - Hedgehog signaling pathway: Epigenetic regulation and role in disease and cancer
      development.
AB  - The evolutionarily conserved Hedgehog (Hh) signaling pathway have critical roles
      in development and homeostasis of tissues. Under physiological conditions, Hh is
      controlled at different levels via stem cell maintenance and tissue regeneration.
      Aberrant activation of this signaling pathway may occur in a wide range of human
      diseases including different types of cancer. In this review we present a concise
      overview on the key genes composing Hh signaling pathway and provide recent
      advances on the molecular mechanisms that regulate Hh signaling pathway from
      extracellular and receptors to the cytoplasmic and nuclear machinery with a
      highlight on the role of microRNAs. Furthermore, we focus on critical studies
      demonstrating dysregulation of the Hh pathway in human disease development, and
      potential therapeutic implications. Finally, we introduce recent therapeutic
      drugs acting as Shh signaling pathway inhibitors, including those in clinical
      trials and preclinical studies.

PMID- 29380373
TI  - Metformin attenuates folic-acid induced renal fibrosis in mice.
AB  - Progressive tubulointerstitial fibrosis has been recognized as a common
      pathological process that leads to the progression of all chronic kidney disease
      (CKD). Innovative strategies are needed to both prevent and treat CKD.
      Inflammatory and fibrotic signaling pathways play central roles in the
      progression of CKD regardless of aetiology. Hence, targeting inflammatory and
      fibrotic responses holds promise to limit renal fibrosis. Metformin has been the
      most prescribed glucose-lowering medicine worldwide, and its potential for many
      other therapeutic applications is also being explored intensively. Increasing
      evidence indicates metformin may limit renal fibrosis. However, the exact
      mechanisms whereby metformin limits renal injury are not fully understood. The
      anti-fibrotic effects of metformin, independent of improved glycaemic control was
      examined in a folic acid-induced mouse model of nephropathy for 14 days. Human
      proximal tubular cells (HK2 cells) exposed to TGF-beta1 were used in in vitro
      models to examine mechanistic pathways. Folic acid induced nephropathy was
      associated with the overexpression of inflammatory markers MCP-1, F4/80, type IV
      collagen, fibronectin and TGF-beta1 compared to control groups, which were
      partially attenuated by metformin treatment. In vitro studies confirmed that
      metformin inhibited TGF-beta1 induced inflammatory and fibrotic responses through
      Smad3, ERK1/2, and P38 pathways in human renal proximal tubular cells. These
      results suggest that metoformin attenuates folic acid-induced renal interstitial
      fibrogenesis through TGF-beta1 signaling pathways.

PMID- 29380374
TI  - Hunger mediates apex predator's risk avoidance response in wildland-urban
      interface.
AB  - Conflicts between large mammalian predators and humans present a challenge to
      conservation efforts, as these events drive human attitudes and policies
      concerning predator species. Unfortunately, generalities portrayed in many
      empirical carnivore landscape selection studies do not provide an explanation for
      a predator's occasional use of residential development preceding a carnivore
      human conflict event. In some cases, predators may perceive residential
      development as a risk-reward trade-off. We examine whether state-dependent
      mortality risk-sensitive foraging can explain an apex carnivore's (Puma concolor)
      occasional utilization of residential areas. We assess whether puma balance the
      risk and rewards in a system characterized by a gradient of housing densities
      ranging from wildland to suburban. Puma GPS location data, characterized as
      hunting and feeding locations, were used to assess landscape variables governing
      hunting success and hunting site selection. Hunting site selection behaviour was
      then analysed conditional on indicators of hunger state. Residential development
      provided a high energetic reward to puma based on increases in prey availability
      and hunting success rates associated with increased housing density. Despite a
      higher energetic reward, hunting site selection analysis indicated that pumas
      generally avoided residential development, a landscape type attributed with
      higher puma mortality risk. However, when a puma experienced periods of extended
      hunger, risk avoidance behaviour towards housing waned. This study demonstrates
      that an apex carnivore faces a trade-off between acquiring energetic rewards and
      avoiding risks associated with human housing. Periods of hunger can help explain
      an apex predator's occasional use of developed landscapes and thus the rare
      conflicts in the wildland-urban interface. Apex carnivore movement behaviours in
      relation to human conflicts are best understood as a three-player community-level
      interaction incorporating wild prey distribution.

PMID- 29380375
TI  - Maternal sensitivity to distress, attachment and the development of callous
      unemotional traits in young children.
AB  - BACKGROUND: Callous-unemotional (CU) traits are characterized by a lack of
      responsiveness to the emotions of others, particularly negative emotions. A
      parenting environment where the child's own distress emotions are sensitively
      responded to may help foster the child's ability to respond to the emotions of
      others. We tested whether maternal sensitivity to distress, and other parenting
      characteristics, were associated with CU traits over the preschool period, and
      examined whether this was mediated via infant attachment status. METHOD: In an
      epidemiological cohort, CU traits were assessed at age 2.5, 3.5, and 5.0 years by
      mother report. Dimensions of parenting were assessed in free play at age 29 weeks
      in a stratified subsample of 272, and attachment status at 14 months (n = 265).
      Structural equation modelling with maximum likelihood estimation was used to
      examine predictions from parenting dimensions and attachment status. RESULTS: A
      parenting factor comprised of sensitivity to distress (n = 207), sensitivity to
      non-distress, positive regard toward the infant (or warmth), and intrusiveness,
      predicted child CU traits (p = .023). This effect was accounted for mainly by
      sensitivity to distress (p = .008) and positive regard (p = .023) which showed a
      synergistic effect as evidenced by a significant interaction (p = .01). This
      arose because the combination of low sensitivity to distress and low positive
      regard created the risk for elevated CU traits. Although sensitivity and positive
      regard predicted attachment security and disorganization, there were no
      associations between attachment status and CU traits. CONCLUSIONS: The finding of
      contributions from both sensitivity to distress and positive regard to reduced CU
      traits suggests that children's responsiveness to others' emotions may be
      increased by their own mothers' responsiveness to them and their mothers' warmth.
      There was no evidence that this was mediated via attachment status. Implications
      for intervention and future directions are discussed.

PMID- 29380376
TI  - Effects of S-1-propenylcysteine, a sulfur compound in aged garlic extract, on
      blood pressure and peripheral circulation in spontaneously hypertensive rats.
AB  - OBJECTIVES: This study was designed to investigate the antihypertensive effect of
      S-1-propenylcysteine, a characteristic sulfur compound in aged garlic extract,
      using a hypertensive rat model. METHODS: The blood pressure and tail blood flow
      of both spontaneously hypertensive rats and control Wistar Kyoto rats were
      measured by the tail-cuff method and the noncontact laser Doppler method,
      respectively, at various times after single oral administration of a test
      compound for 24 h. KEY FINDINGS: Treatment with S-1-propenylcysteine (6.5 mg/kg
      BW) significantly decreased the systolic blood pressure of spontaneously
      hypertensive rat approximately 10% at 3 h after administration, and thereafter,
      the systolic blood pressure gradually returned to the baseline level in 24 h. The
      effect of S-1-propenylcysteine was dose-dependent and was maximal at the dose of
      6.5 mg/kg BW at 3 h. However, the other compounds such as S-allylcysteine and S
      allylmercaptocysteine in aged garlic extract were ineffective. In addition, S-1
      propenylcysteine had no effect on systolic blood pressure of control Wistar Kyoto
      rats. Furthermore, S-1-propenylcysteine significantly increased the blood flow at
      3 h after administration at the dose of 6.5 mg/kg BW. CONCLUSIONS: S-1
      propenylcysteine is a key constituent of aged garlic extract responsible for its
      antihypertensive effect, and the effect of S-1-propenylcysteine involves the
      improvement in peripheral circulation.

PMID- 29380378
TI  - Auditory DUM neurons in a bush-cricket: A filter bank for carrier frequency.
AB  - In bush-crickets the first stage of central auditory processing occurs in the
      prothoracic ganglion. About 15 to 50 different auditory dorsal unpaired median
      neurons (DUM neurons) exist but they have not been studied in any detail. These
      DUM neurons may be classified into seven different morphological types, although,
      there is only limited correlation between morphology and physiological responses.
      Ninety seven percent of the stained neurons were local, 3% were intersegmental.
      About 90% project nearly exclusively into the auditory neuropile, and 45% into
      restricted areas therein. Lateral extensions overlap with the axons of primary
      auditory sensory neurons close to their branching point. DUM neurons are
      typically tuned to frequencies covering the range between 2 and 50 kHz and
      thereby may establish a filter bank for carrier frequency. Less than 10% of DUM
      neurons have their branches in adjacent and more posterior regions of the
      auditory neuropile and are mostly tuned to low frequencies, less sensitive than
      the other types and respond to vibration. Thirty five percent of DUM show
      indications of inhibition, either through reduced responses at higher
      intensities, or by hyperpolarizing responses to sound. Most DUM neurons produce
      phasic spike responses preferably at higher intensities. Spikes may be elicited
      by intracellular current injection. Preliminary data suggest that auditory DUM
      neurons have GABA as transmitter and therefore may inhibit other auditory
      interneurons. From all known local auditory neurons, only DUM neurons have
      frequency specific responses which appear suited for local processing relevant
      for acoustic communication in bush crickets.

PMID- 29380377
TI  - Imbalance of synaptic actin dynamics as a key to fragile X syndrome?
AB  - Our experiences and memories define who we are, and evidence has accumulated that
      memory formation is dependent on functional and structural adaptations of
      synaptic structures in our brain. Especially dendritic spines, the postsynaptic
      compartments of synapses show a strong structure-to-function relationship and a
      high degree of structural plasticity. Although the molecular mechanisms are not
      completely understood, it is known that these modifications are highly dependent
      on the actin cytoskeleton, the major cytoskeletal component of the spine. Given
      the crucial involvement of actin in these mechanisms, dysregulations of spine
      actin dynamics (reflected by alterations in dendritic spine morphology) can be
      found in a variety of neurological disorders ranging from schizophrenia to
      several forms of autism spectrum disorders such as fragile X syndrome (FXS). FXS
      is caused by a single mutation leading to an inactivation of the X-linked fragile
      X mental retardation 1 gene and loss of its gene product, the RNA-binding protein
      fragile X mental retardation protein 1 (FMRP), which normally can be found both
      pre- and postsynaptically. FMRP is involved in mRNA transport as well as
      regulation of local translation at the synapse, and although hundreds of FMRP
      target mRNAs could be identified only a very few interactions between FMRP and
      actin-regulating proteins have been reported and validated. In this review we
      give an overview of recent work by our lab and others providing evidence that
      dysregulated actin dynamics might indeed be at the very base of a deeper
      understanding of neurological disorders ranging from cognitive impairment to the
      autism spectrum.

PMID- 29380379
TI  - High-throughput oxidation screen of antibody-drug conjugates by analytical
      protein A chromatography following IdeS digest.
AB  - OBJECTIVES: Oxidation of protein therapeutics is a major chemical degradation
      pathway which may impact bioactivity, serum half-life and stability. Therefore,
      oxidation is a relevant parameter which has to be monitored throughout
      formulation development. Methods such as HIC, RPLC and LC/MS achieve a separation
      of oxidized and non-oxidized species by differences in hydrophobicity. Antibody
      drug conjugates (ADC) although are highly more complex due to the heterogeneity
      in linker, drug, drug-to-antibody ratio (DAR) and conjugation site. The
      analytical protein A chromatography can provide a simple and fast alternative to
      these common methods. METHODS: A miniature analytical protein A chromatography
      method in combination with an IdeS digest was developed to analyse ADCs. The IdeS
      digest efficiency of an IgG1 was monitored using SEC-HPLC and non-reducing SDS
      PAGE. An antibody-fluorescent dye conjugate was conjugated at different dye-to
      antibody ratios as model construct to mimic an ADC. KEY FINDINGS: With IdeS, an
      almost complete digest of a model IgG1 can be achieved (digested protein amount
      >98%). This enables subsequent analytical protein A chromatography, which
      consequently eliminates any interference of payload with the stationary phase.
      CONCLUSION: A novel high-throughput method for an interchain cysteine-linked ADC
      oxidation screens during formulation development was developed.

PMID- 29380380
TI  - Cervical myelopathy due to complex Atlanto-axial malformation including partial
      atlantal dorsal arch aplasia in a domestic rabbit.
AB  - A 1-year-old dwarf rabbit was presented with sub-acute progressive tetraparesis.
      Radiography, CT and MRI revealed compressive cervical myelopathy secondary to a
      complex atlanto-axial malformation including partial aplasia of the atlantal
      dorsal arch, dens malformation, malarticulation and lateral atlanto-occipital
      displacement. Owners decided against surgical treatment and elected conservative
      treatment including analgesia with non-steroidal anti-inflammatory drugs, cage
      rest and physiotherapy. Within 2 months clinical signs deteriorated and the owner
      elected euthanasia. Subsequent necropsy confirmed imaging findings. Similar cases
      described in humans and dogs suggest that partial aplasia of the dorsal arch of
      the atlas might often be an asymptomatic radiologic finding in these species. In
      contrast, this first description of a similarly affected rabbit demonstrates that
      complex atlanto-axial malformations can cause severe clinical signs.

PMID- 29380381
TI  - Prevalence of burnout among nurses in Iran: a systematic review and meta
      analysis.
AB  - AIM: This study aimed to summarize the available information in the literature to
      make an accurate estimate of the prevalence of burnout among Iranian nurses.
      BACKGROUND AND INTRODUCTION: Burnout is a work-related stress syndrome that has
      negative impact on healthcare providers, patients and healthcare delivery
      systems. METHOD: A comprehensive search of literature using international
      [PubMed, Scopus and the Institute for Scientific Information (ISI)] and Iranian
      scientific data bases [Scientific Information Database (SID), IranMedex and
      Magiran] was conducted to identify English and Persian language studies,
      published between 2000 and 2016, that examined the prevalence of burnout among
      nurses in Iran. The I-squared test and Chi-squared-based Q-test suggested
      heterogeneity of reported prevalence among the qualified studies; thus, a random
      effects model was applied to estimate the overall prevalence of burnout among
      nurses in Iran. RESULTS: Based on 21 selected articles with 4180 participants,
      the overall prevalence of burnout among Iranian nurses was estimated to be 36%
      [95% confidence interval (CI), 20-53%] in Iran. Meta-regression indicated that
      sample size and year of data collection, mean age of samples, female to male
      ratio and geographic regions were not statistically significantly associated with
      the prevalence of burnout. Also, based on Egger's test and funnel plot, there is
      no publication bias among studies included in the analysis. CONCLUSION:
      Professional burnout affects more than one-third of nursing staff in Iran; thus,
      effective interventions and strategies are required to reduce and prevent burnout
      among nurses. IMPLICATION FOR NURSING AND HEALTH POLICY: Due to the negative
      consequences of burnout on patients, nurses and organizations, nursing and
      healthcare managers should intervene to prevent and reduce burnout among nurses
      in Iran. Policy attention should focus on developing effective interventions to
      prevent and minimize the burden of burnout among nurses in Iran. Nurses'
      involvement in the policy-making process is crucial in the implementation of
      effective programs and initiatives tailored to address the higher prevalence of
      burnout among Iranian nurses.

PMID- 29380382
TI  - Decreases in beetle body size linked to climate change and warming temperatures.
AB  - Body size is a fundamental ecological trait and is correlated with population
      dynamics, community structure and function, and ecosystem fluxes. Laboratory data
      from broad taxonomic groups suggest that a widespread response to a warming world
      may be an overall decrease in organism body size. However, given the myriad of
      biotic and abiotic factors that can also influence organism body size in the
      wild, it is unclear whether results from these laboratory assays hold in nature.
      Here we use datasets spanning 30 to 100 years to examine whether the body size of
      wild-caught beetles has changed over time, whether body size changes are
      correlated with increased temperatures, and we frame these results using
      predictions derived from a quantitative review of laboratory responses of 22
      beetle species to temperature. We found that 95% of laboratory-reared beetles
      decreased in size with increased rearing temperature, with larger-bodied species
      shrinking disproportionately more than smaller-bodied beetles. In addition, the
      museum datasets revealed that larger-bodied beetle species have decreased in size
      over time, that mean beetle body size explains much of the interspecific
      variation in beetle responses to temperature, and that long-term beetle size
      changes are explained by increases in autumn temperature and decreases in spring
      temperature in this region. Our data demonstrate that the relationship between
      body size and temperature of wild-caught beetles matches relatively well with
      results from laboratory studies, and that variation in this relationship is
      largely explained by interspecific variation in mean beetle body size. This long
      term beetle dataset is one of the most comprehensive arthropod body size datasets
      compiled to date, it improves predictions regarding the shrinking of organisms
      with global climate change, and together with the meta-analysis data, call for
      new hypotheses to explain why larger-bodied organisms may be more sensitive to
      temperature.

PMID- 29380383
TI  - CB1 cannabinoid receptor ligands augment the antidepressant-like activity of
      biometals (magnesium and zinc) in the behavioural tests.
AB  - OBJECTIVE: During the last few decades, endocannabinoid system has emerged as a
      novel possible target for antidepressant treatment. Although the medical
      literature provides information on the mood-changing effects of CB1 ligands,
      little is known about the possible interaction between the simultaneous
      activation or inhibition of the CB1 receptor and administration of other agents
      that possess antidepressant potential. The main goal of our study was to evaluate
      the influence of the CB1 cannabinoid receptor ligands (oleamide - an endogenous
      agonist and AM251 - an inverse agonist/antagonist) on the antidepressant-like
      activity of biometals (i.e. magnesium and zinc). METHODS: The forced swim test
      and the tail suspension test in mice were used to determine the antidepressant
      like activity. KEY FINDINGS: Concomitant intraperitoneal administration of per se
      inactive doses of oleamide (5 mg/kg) or AM251 (0.25 mg/kg) and the tested
      biometals (i.e. magnesium, 10 mg/kg or zinc, 5 mg/kg) shortened the immobility
      time of animals in the forced swim test and the tail suspension test. The
      observed effect was not associated with an increase in spontaneous locomotor
      activity of mice. CONCLUSIONS: The simultaneous modulation of the cannabinoid
      system and supplementation of magnesium or zinc produce at least additive
      antidepressant-like effect.

PMID- 29380384
TI  - Nano-engineering of biomedical prednisolone liposomes: evaluation of the
      cytotoxic effect on human colon carcinoma cell lines.
AB  - OBJECTIVES: Liposomes have attracted the attention of researchers due to their
      potential to act as drug delivery systems for cancer treatment. The present
      investigation aimed to develop liposomes loaded with prednisolone base and the
      evaluation of the antiproliferative effect on human colon carcinoma cell lines.
      METHODS: Liposomes were elaborated by following a reproducible thin film
      hydration technique. The physicochemical characterization of liposomes included
      photon correlation spectroscopy, microscopy analysis, Fourier transform infrared
      spectroscopy, rheological behaviour and electrophoresis. On the basis of these
      data and drug loading values, the best formulation was selected. Stability and
      drug release properties were also tested. KEY FINDINGS: Resulting liposomes
      exhibited optimal physicochemical and stability properties, an excellent
      haemocompatibility and direct antiproliferative effect on human colon carcinoma T
      84 cell lines. CONCLUSIONS: This study shows direct antitumour effect of
      prednisolone liposomal formulation, which opens the door for liposomal
      glucocorticoids as novel antitumour agents.

PMID- 29380385
TI  - Role of l-arginine/SNAP/NO/cGMP/KATP channel signalling pathway in
      antinociceptive effect of alpha-terpineol in mice.
AB  - OBJECTIVES: The main purpose of this study was to assess the role of l
      arginine/SNAP/NO/cGMP/KATP channel pathway in analgesic effects of alpha
      terpineol in mice. METHODS: Male NMRI mice were pretreated intraperitoneally with
      NO precursor (l-arginine, 100 mg/kg), NO synthase inhibitor (l-NAME, 30 mg/kg),
      NO donor (SNAP, 1 mg/kg), guanylyl cyclase inhibitor (methylene blue, 20 mg/kg),
      PDE inhibitor (sildenafil, 0.5 mg/kg), KATP channel blocker (glibenclamide, 10
      mg/kg) and naloxone (2 mg/kg) 20 min before the administration of alpha
      terpineol. The formalin test was performed 20 min after the administration of
      alpha-terpineol, and nociceptive responses of mice were recorded during 30 min.
      KEY FINDINGS: A significant and dose-dependent antinociception was produced by
      alpha-terpineol (40 and 80 mg/kg) in both the phases of formalin test. The
      antinociceptive effect of alpha-terpineol was significantly potentiated by l
      arginine in the second phase while significantly antagonized by l-NAME in both
      phases of formalin test. Also, SNAP and sildenafil non-significantly enhanced
      while methylene blue significantly diminished-the antinociceptive effect of alpha
      terpineol in both phases of formalin test. Glibenclamide significantly reversed
      the alpha-terpineol-induced antinociception, indicating the involvement of KATP
      channels in antinociceptive effect of alpha-terpineol. CONCLUSIONS: These results
      indicate that the antinociceptive effect of alpha-terpineol is mediated through l
      arginine/SNAP/NO/cGMP/KATP channel pathway.

PMID- 29380386
TI  - The detection of higher-order acoustic transitions is reflected in the N1 ERP.
AB  - The auditory system features various types of dedicated change detectors enabling
      the rapid parsing of auditory stimulation into distinct events. The activity of
      such detectors is reflected by the N1 ERP. Interestingly, certain acoustic
      transitions show an asymmetric N1 elicitation pattern: whereas first-order
      transitions (e.g., a change from a segment of constant frequency to a frequency
      glide [c-to-g change]) elicit N1, higher-order transitions (e.g., glide-to
      constant [g-to-c] changes) do not. Consensus attributes this asymmetry to the
      absence of any available sensory mechanism that is able to rapidly detect higher
      order changes. In contrast, our study provides compelling evidence for such a
      mechanism. We collected electrophysiological and behavioral data in a transient
      detection paradigm. In each condition, a random (50%-50%) sequence of two types
      of tones occurred, which did or did not contain a transition (e.g., c-to-g and
      constant stimuli or g-to-c and glide tones). Additionally, the rate of pitch
      change of the glide varied (i.e., 10 vs. 40 semitones per second) in order to
      increase the number of responding neural assemblies. The rate manipulation
      modulated transient ERPs and behavioral detection performance for g-to-c
      transitions much stronger than for c-to-g transitions. The topographic and
      tomographic analyses suggest that the N1 response to c-to-g and also to g-to-c
      transitions emerged from the superior temporal gyrus. This strongly supports a
      sensory mechanism that allows the fast detection of higher-order changes.

PMID- 29380387
TI  - Platelet sequestration with a new-generation autotransfusion device.
AB  - BACKGROUND: Autologous platelet-rich plasma (PRP) can be used either to prevent
      platelets (PLTs) from lesions during extracorporeal circulation or for wound
      therapy, when processed into PLT gel. The aim of this study was to evaluate the
      PLT sequestration abilities of a new-generation autotransfusion device. STUDY
      DESIGN AND METHODS: In this experimental study the discontinuous, new-generation
      autotransfusion device XTRA was evaluated using fresh donor blood. The blood was
      processed in four different size bowls (X55, X125, X175, X225 [bowls' size in
      mL]) using the device's built-in "PLT sequestration program." PLT functionality
      was tested using aggregometry; for PLT activation, beta-thromboglobulin (beta-TG)
      and soluble P-selectin levels were determined. Cell damage was assessed by a
      morphology score and hypotonic shock response. Additionally, PLTs were tested
      after 6 hours to identify storage lesions. RESULTS: Platelet recovery in the PRP
      ranged from 39% to 64% and averaged 6.2-fold PLT enrichment as defined by the
      increase in PLT concentration. The preparation caused minimal cell damage and a
      decrease in cell function by only 10%, but a slight activation was observed
      amounting to 9% of the maximal beta-TG release. The efficiency of the
      preparation, represented by the PLT recovery rate, increased in a linear fashion
      with the increasing bowl sizes being tested. After 6 hours of storage the
      prepared PLTs showed an additional 9% loss in function, but only 4% decrease in
      viability. CONCLUSION: The autotransfusion device XTRA was capable of high
      quality perioperative PRP preparation, and the bowl size was found to have an
      influence on the efficiency of the preparation.

PMID- 29380388
TI  - Head-to-head comparison of acute and chronic pulmonary vein stenosis for
      cryoballoon versus radiofrequency ablation.
AB  - BACKGROUND: Cryoballoon (CB) applications to pulmonary veins (PVs) can cause
      stenosis just as radiofrequency (RF) energy deliveries. The goal of the present
      study was to clarify whether or not there was any difference in the extent of
      acute or chronic PV narrowing after PV isolation between the two different energy
      sources. METHODS: Consecutive patients with paroxysmal atrial fibrillation who
      were scheduled to undergo a PV isolation were randomized 1:1 to receive CB or RF
      ablation. The endpoints were any acute PV narrowing assessed with the use of
      intracardiac ultrasound during the procedure and PV stenosis measured with
      cardiac computed tomography at the 3-month follow-up. RESULTS: An acute reduction
      in the luminal area of the left superior PV (mean +/- standard deviation, -6.8 +/
      8.7 vs -19.9 +/- 14.7%; P < 0.001) and left inferior PV (-5.1 +/- 20.2 vs -15.3
      +/- 11.6%; P = 0.03) was significantly smaller in the CB arm (N = 25) than the RF
      arm (N = 25). There was no difference in the extent of PV stenosis 3 months after
      the ablation between the arms (0-25% stenosis, 90% vs 88%, 25-50% stenosis, 10%
      vs 12%, >50% stenosis, both 0%; P = 0.82). A greater acute PV narrowing was
      likely to lead to chronic stenosis in the RF arm (P = 0.004). CONCLUSIONS: CB
      ablation may reduce the acute narrowing of the left-sided PVs as compared to RF
      ablation.

PMID- 29380389
TI  - Phosphorus concentration coordinates a respiratory bypass, synthesis and
      exudation of citrate, and the expression of high-affinity phosphorus transporters
      in Solanum lycopersicum.
AB  - Plants exhibit respiratory bypasses (e.g., the alternative oxidase [AOX]) and
      increase the synthesis of carboxylates in their organs (leaves and roots) in
      response to phosphorus (P) deficiency, which increases P uptake capacity. They
      also show differential expression of high-affinity inorganic phosphorus (Pi)
      transporters, thus avoiding P toxicity at a high P availability. The association
      between AOX and carboxylate synthesis was tested in Solanum lycopersicum plants
      grown at different soil P availability, by using plants grown under P-sufficient
      and P-limiting conditions and by applying a short-term (24 hr) P-sufficient pulse
      to plants grown under P limitation. Tests were also performed with plants
      colonized with arbuscular mycorrhizal fungi, which increased plant P
      concentration under reduced P availability. The in vivo activities of AOX and
      cytochrome oxidase were measured together with the concentration of carboxylates
      and the P concentration in plant organs. Gene transcription of Pi transporters
      (LePT1 and LePT2) was also studied. A coordinated response between plant P
      concentration with these traits was observed, indicating that a sufficient P
      availability in soil led to a suppression of both AOX activity and synthesis of
      citrate and a downregulation of the transcription of genes encoding high-affinity
      Pi transporters, presumably to avoid P toxicity.

PMID- 29380390
TI  - EAACI guidelines on allergen immunotherapy: Executive statement.

PMID- 29380391
TI  - RSV-hRV co-infection is a risk factor for recurrent bronchial obstruction and
      early sensitization 3 years after bronchiolitis.
AB  - To assess risk factors of recurrent bronchial obstruction and allergic
      sensitization 3 years after an episode of acute bronchiolitis, whether after
      ambulatory care treatment or hospitalization. A monocentric prospective
      longitudinal study including infants aged under 1 year with acute bronchiolitis
      was performed, with clinical (severity score), biological (serum Krebs von den
      Lungen 6 antigen), and viral (14 virus by naso-pharyngeal suction detection)
      assessments. Follow-up included a quaterly telephone interview, and a final
      clinical examination at 3 years. Biological markers of atopy were also measured
      in peripheral blood, including specific IgEs towards aero- and food allergens.
      Complete data were available for 154 children. 46.8% of them had recurrent
      wheezing (RW). No difference was found according to initial severity, care at
      home or in the hospital, respiratory virus involved, or existence of co
      infection. A familial history of atopy was identified as a risk factor for
      recurrent bronchial obstruction (60% for RW infants versus 39%, P = 0.02), as
      living in an apartment (35% versus 15%, P = 0.002). 18.6% of the infants were
      sensitized, with 48.1% of them sensitized to aeroallergens and 81.5% to food
      allergens. Multivariate analysis confirmed that a familial history of atopy (P =
      0.02) and initial co-infection RSV-hRV (P = 0.02) were correlated with the risk
      of sensitization to aeroallergens at 3 years. Familial history of atopy and RSV
      hRV co-infection are risk factors for recurrent bronchial obstruction and
      sensitization.

PMID- 29380393
TI  - Leishmania amazonensis induces modulation of costimulatory and surface marker
      molecules in human macrophages.
AB  - Manipulation of costimulatory and surface molecules that shape the extent of
      immune responses by Leishmania is suggested as one of the mechanisms of evading
      the host's defences. The experiments reported here were designed to evaluate the
      expressions of CD11b, CD11c, CD14, CD18, CD54, CD80, CD86, CD206, MHC class II
      and TLR-2 (Toll-like receptor 2) in human macrophages infected with L.
      amazonensis. Phenotypic evaluation revealed a negative modulation in CD11b,
      CD11c, CD14, CD18, CD54 and MHC class II molecules, depending on the level of
      infection. The results showed that as early as 1 hour after infection no
      reduction in marker expression occurs, whereas after 24 hours, downregulation of
      these molecules was observed in macrophages. No significant changes were observed
      in the expressions of CD80, CD86, CD206 and TLR2. Evidence of the differential
      modulation of markers expression and that after parasite uptake no reduction in
      surface marker expression occurs indicates that parasite internalization is not
      involved in the phenomena of down-modulation.

PMID- 29380392
TI  - Prediction of the severity of allergic reactions to foods.
AB  - BACKGROUND: There is currently considerable uncertainty regarding what the
      predictors of the severity of diagnostic or accidental food allergic reactions
      are, and to what extent the severity of such reactions can be predicted.
      OBJECTIVE: To identify predictors for the severity of diagnostic and accidental
      food allergic reactions and to quantify their impact. METHODS: The study
      population consisted of children with a double-blind, placebo-controlled food
      challenge (DBPCFC)-confirmed food allergy to milk, egg, peanut, cashew nut,
      and/or hazelnut. The data were analyzed using multiple linear regression
      analysis. Missing values were imputed using multiple imputation techniques. Two
      scoring systems were used to determine the severity of the reactions. RESULTS: A
      total of 734 children were included. Independent predictors for the severity of
      the DBPCFC reaction were age (B = 0.04, P = .001), skin prick test ratio (B =
      0.30, P < .001), eliciting dose (B = -0.09, P < .001), level of specific
      immunoglobulin E (B = 0.15, P < .001), reaction time during the DBPCFC (B = 
      0.01, P = .004), and severity of accidental reaction (B = 0.08, P = .015). The
      total explained variance of this model was 23.5%, and the eliciting dose only
      contributed 4.4% to the model. Independent predictors for more severe accidental
      reactions with an explained variance of 7.3% were age (B = 0.03, P = .014), milk
      as causative food (B = 0.77, P < .001), cashew as causative food (B = 0.54, P <
      .001), history of atopic dermatitis (B = -0.47, P = .006), and severity of DBPCFC
      reaction (B = 0.12, P = .003). CONCLUSIONS: The severity of DBPCFCs and
      accidental reactions to food remains largely unpredictable. Clinicians should not
      use the eliciting dose obtained from a graded food challenge for the purposes of
      making risk-related management decisions.

PMID- 29380394
TI  - Assessing our current practice: point prevalence studies in transfusion medicine.

PMID- 29380395
TI  - Prolonged corrected QT interval in predicting atrial fibrillation: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Corrected QT interval (QTc) on the electrocardiogram is a marker of
      ventricular repolarization. Recent studies have examined its value in predicting
      the occurrence of atrial fibrillation (AF). METHODS AND RESULTS: We conducted a
      meta-analysis to determine whether alterations in QTc interval are associated
      with an increased risk of incident AF. The PUBMED and EMBASE databases were
      searched for all studies that evaluated the incident AF associated with prolonged
      QTc interval published before December 2016. Sensitivity and subgroup analysis
      were subsequently performed. A total of six studies including eight data sets for
      prolonged QTc interval were eligible. Subjects with prolonged QTc interval as a
      categorical variable had a significantly higher risk of AF during follow-up
      (hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.09-1.24, I2  = 90%)
      based on Bazett formula. In continuous variable analysis, we found a
      statistically significant risk for AF (HR, 1.17; 95% CI, 1.09-1.25; I2  = 0)
      every 10-ms prolongation in QTc. AF type, QTc cut-off value, geographical
      location, follow-up duration, and study population may be the possible reasons
      for the significant heterogeneity among the studies. CONCLUSIONS: Prolonged QTc
      interval is associated with an increased risk of AF. And the potential mechanisms
      underlying this cause-and-effect relationship need further investigation.

PMID- 29380396
TI  - Molecular genetic identification of isolates of the hepatitis A virus (HAV) from
      monkeys at Adler Primate Center.
AB  - BACKGROUND: The aim of this study was to assess prevalence and genetic
      variability of hepatitis A virus (HAV) isolates in monkeys born and kept at Adler
      Primate Center, as well as in imported animals. METHODS: The fecal samples from
      various species of monkeys (n = 119) were studied using reverse transcription
      seminested PCR, sequencing, and phylogenetic analysis. RESULTS: HAV RNA was
      detected in 2 Macaca mulatta and 1 Macaca fascicularis (3.8%) kept at Adler
      Primate Center (n = 79) and in 11 (27.5%) Chlorocebus pygerythrus (n = 40)
      imported from Tanzania. Phylogenetic analysis demonstrated that all HAV strains
      belonged to simian genotype V, but differed from the prototype genotype V strain
      (AGM-27) by 5.4%-5.5%. Sequences isolated in this study differed by only 0.1%,
      suggesting a common source of infection. CONCLUSIONS: This study demonstrated the
      asymptomatic circulation of HAV genotype V among the monkeys at Adler Primate
      Center, and it indicated the significant genetic diversity within this HAV
      genotype.

PMID- 29380397
TI  - Effects of inorganic mercury exposure on histological structure, antioxidant
      status and immune response of immune organs in yellow catfish (Pelteobagrus
      fulvidraco).
AB  - Mercury (Hg) is well recognized as a highly toxic substance to fish.
      Nevertheless, little is known about the toxic effects of Hg on immune organs. In
      this study, we investigated histology, antioxidant status and immune response of
      the spleen and head kidney in yellow catfish following 6 weeks of exposure to
      environmentally relevant concentrations of inorganic Hg (2 and 10 MUg l-1 Hg2+ ).
      As expected, Hg accumulation and histological injury in both tissues were
      observed. Meanwhile, Hg2+ exposure induced oxidative stress, which increased
      antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase)
      activities, glutathione content, anti-hydroxyl radical capacity and the
      expression of genes associated with antioxidant (sod1, cat, gpx1, nrf2 and mt)
      and stress (hsp70) responses in dose- and tissue-specific manners. In the spleen,
      the mRNA levels of immune-related genes (il-1beta, il-8, tnf-alpha, il-10, tgf
      beta, lys and c3) were upregulated by Hg2+ exposure. However, in the head kidney,
      upregulation of tnf-alpha, il-10 and tgf-beta mRNAs and downregulation of il
      1beta and lys expressions were observed, while transcriptions of il-8 and c3 were
      remarkably upregulated only in the 2 MUg l-1 group. Overall, our study indicated
      that Hg2+ exposure could result in Hg accumulation and thereby induced
      histological impairment, oxidative stress and immunotoxicity in immune organs of
      yellow catfish, but some enzymes and/or genes involved in antioxidant and immune
      systems would be activated to resist Hg2+ -induced damage.

PMID- 29380398
TI  - Warming reduces the cover, richness and evenness of lichen-dominated biocrusts
      but promotes moss growth: insights from an 8 yr experiment.
AB  - Despite the important role that biocrust communities play in maintaining
      ecosystem structure and functioning in drylands world-wide, few studies have
      evaluated how climate change will affect them. Using data from an 8-yr-old
      manipulative field experiment located in central Spain, we evaluated how warming,
      rainfall exclusion and their combination affected the dynamics of biocrust
      communities in areas that initially had low (< 20%, LIBC plots) and high (> 50%,
      HIBC plots) biocrust cover. Warming reduced the richness (35 +/- 6%), diversity
      (25 +/- 8%) and cover (82 +/- 5%) of biocrusts in HIBC plots. The presence and
      abundance of mosses increased with warming through time in these plots, although
      their growth rate was much lower than the rate of lichen death, resulting in a
      net loss of biocrust cover. On average, warming caused a decrease in the
      abundance (64 +/- 7%) and presence (38 +/- 24%) of species in the HIBC plots.
      Over time, lichens and mosses colonized the LIBC plots, but this process was
      hampered by warming in the case of lichens. The observed reductions in the cover
      and diversity of lichen-dominated biocrusts with warming will lessen the capacity
      of drylands such as that studied here to sequester atmospheric CO2 and to provide
      other key ecosystem services associated to these communities.

PMID- 29380399
TI  - Immunohistochemical assessment of the diagnostic utility of PD-L1: a preliminary
      analysis of anti-PD-L1 antibody (SP142) for lymphoproliferative diseases with
      tumour and non-malignant Hodgkin-Reed-Sternberg (HRS)-like cells.
AB  - AIMS: The programmed death 1 (PD1)/PD1 ligand (PD-L1) axis plays an important
      role in tumour cells escape from immune control. PD-L1 immunohistochemistry is a
      useful predictor of immunotherapy response, but is still not used widely in the
      diagnostic setting. Here we describe results using PD-L1 immunohistochemistry
      during routine diagnostics in lymphoma. METHODS AND RESULTS: Ninety-one
      lymphoproliferative disease cases sharing tumour and non-malignant Hodgkin-Reed
      Sternberg (HRS)-like cells with and without Epstein-Barr virus (EBV) association
      were investigated by immunohistochemistry for PD-L1 (clone SP142). PD-L1
      expression was present in more than 5% of tumour or non-malignant HRS-like cells
      in 100% of EBV+ classical (C) Hodgkin lymphoma (HL) (n = 10) and EBV-negative
      nodular sclerosis CHL (n = 8); 40% of EBV+ diffuse large B cell lymphoma, not
      otherwise specified (DLBCL-NOS) (n = 20); and 4% of nodal peripheral T cell
      lymphoma of follicular helper T cell type (PTCL-TFH) (n = 22). In contrast,
      nodular lymphocyte-predominant HL (n = 4), lymphocyte-rich CHL (n = 6), EBV+
      hyperplasia (n = 8), plasmablastic lymphoma (n = 3) and anaplastic lymphoma
      kinase-negative anaplastic large cell lymphoma (n = 5) seldom exhibited PD-L1 in
      their large cells. Assessing PD-L1 positivity in tumour and non-malignant large
      cells was helpful in differentiating between CHL versus nodal PTCL-TFH (P <
      0.0001) or EBV+ DLBCL-NOS (P = 0.0052) and between EBV+ DLBCL-NOS versus nodal
      PTCL-TFH (P = 0.0052), with PD-L1 expression indicating the first diagnosis in
      each of those sets. CONCLUSION: Immunohistochemical evaluation of PD-L1
      expression in tumour and non-malignant HRS-like large cells may be useful for
      assessing either immune escape or immunodeficiency in their pathogenesis.

PMID- 29380400
TI  - Ursolic acid derivatives as potential antidiabetic agents: In vitro, in vivo, and
      in silico studies.
AB  - Hit, Lead & Candidate Discovery Protein tyrosine phosphatase 1B (PTP-1B) has
      attracted interest as a novel target for the treatment of type 2 diabetes, this
      because its role in the insulin-signaling pathway as a negative regulator. Thus,
      the aim of current work was to obtain seven ursolic acid derivatives as potential
      antidiabetic agents with PTP-1B inhibition as main mechanism of action.
      Furthermore, derivatives 1-7 were submitted in vitro to enzymatic PTP-1B
      inhibition being 3, 5, and 7 the most active compounds (IC50  = 5.6, 4.7, and 4.6
      MUM, respectively). In addition, results were corroborated with in silico docking
      studies with PTP-1B orthosteric site A and extended binding site B, showed that 3
      had polar and Van der Waals interactions in both sites with Lys120, Tyr46,
      Ser216, Ala217, Ile219, Asp181, Phe182, Gln262, Val49, Met258, and Gly259,
      showing a docking score value of -7.48 Kcal/mol, being more specific for site A.
      Moreover, compound 7 showed polar interaction with Gln262 and Van der Waals
      interactions with Ala217, Phe182, Ile219, Arg45, Tyr46, Arg47, Asp48, and Val49
      with a predictive docking score of -6.43 kcal/mol, suggesting that the potential
      binding site could be localized in the site B adjacent to the catalytic site A.
      Finally, derivatives 2 and 7 (50 mg/kg) were selected to establish their in vivo
      antidiabetic effect using a noninsulin-dependent diabetes mice model, showing
      significant blood glucose lowering compared with control group (p < .05).

PMID- 29380401
TI  - Patients with psoriasis are frequently using sunbeds.

PMID- 29380402
TI  - Epothilone D accelerates disease progression in the SOD1G93A mouse model of
      amyotrophic lateral sclerosis.
AB  - AIMS: Degeneration of the distal neuromuscular circuitry is a hallmark pathology
      of Amyotrophic Lateral Sclerosis (ALS). The potential for microtubule dysfunction
      to be a critical pathophysiological mechanism in the destruction of this
      circuitry is increasingly being appreciated. Stabilization of microtubules to
      improve neuronal integrity and pathology has been shown to be a particularly
      favourable approach in other neurodegenerative diseases. We present evidence here
      that treatment with the microtubule-targeting compound Epothilone D (EpoD) both
      positively and negatively affects the spinal neuromuscular circuitry in the
      SOD1G93A mouse model of ALS. METHODS: SOD1G93A mice were treated every 5 days
      with 2 mg/kg EpoD. Evaluation of motor behaviour, neurological phenotype and
      survival was completed, with age-dependent histological characterization also
      conducted, using the thy1-YFP mouse. Motor neuron degeneration, axonal integrity,
      neuromuscular junction (NMJ) health and gliosis were also assessed. RESULTS: EpoD
      treatment prevented loss of the spinal motor neuron soma, and distal axon
      degeneration, early in the disease course. This, however, was not associated with
      protection of the NMJ synapse and did not improve motor phenotype or clinical
      progression. EpoD administration was also found to be neurotoxic at later disease
      stages. This was evidenced by accelerated motor neuron cell body loss, increasing
      gliosis, and was associated with detrimental outcomes to motor behaviour,
      clinical assessment and survival. CONCLUSIONS: The results suggest that EpoD
      accelerates disease progression in the SOD1G93A mouse model of ALS, and
      highlights that the pathophysiological involvement of microtubules in ALS is an
      evolving and underappreciated phenomenon.

PMID- 29380403
TI  - Simultaneous detection of barrier- and immune-related gene variations in patients
      with atopic dermatitis by reverse blot hybridization assay.
AB  - BACKGROUND: Hereditary factors are involved in the pathogenesis of atopic
      dermatitis (AD). However, AD-related gene variations are significantly different
      across ethnicities. AIM: To identify mutations and single-nucleotide
      polymorphisms (SNPs) in barrier- or immune-related genes from Korean patients
      with AD and compare the variations with those observed in nonatopic healthy
      controls (HCs), and to use novel reverse blot hybridization assay (REBA) for AD
      related gene variants. METHODS: We carried out REBA to simultaneously detect
      variations in genes related to barrier or immune function, namely, FLG, SPINK5,
      KLK7, DEFB1, TNFalpha, KDR, FCER1A, IL4, IL5,IL5RA, IL9, IL10, IL12, IL12R, IL13
      and IL18, from Korean patients with AD, and compared the variation to that in
      nonatopic healthy controls. RESULTS: The homozygous mutants of KLK7 and SPINK5
      2475, and the heterozygous mutants of FLG 3321delA, SPINK5-1156, DEFB1, KDR,
      IL5RA, IL9 and IL12RB1 were significantly more frequent in AD. It has been
      predicted that the larger the number of gene variants, the higher the odds ratio
      of AD prevalence; however, we did not find any significant correlation between
      the number of gene variants and AD severity. CONCLUSION: Using REBA, we
      identified more genetic variants that can predict AD occurrence. We also verified
      that REBA can be used to easily and accurately detect multiple AD-related gene
      variants simultaneously. In addition, we identified a correlation between KLK7
      mutation and AD in Koreans, which is the first such report, to our knowledge.

PMID- 29380404
TI  - Contrast-Enhanced Ultrasonography Versus Contrast-Enhanced Computed Tomography
      for Assessment of Residual Tumor From Hepatocellular Carcinoma Treated With
      Transarterial Chemoembolization: A Meta-analysis.
AB  - OBJECTIVES: This study reviewed the literature to directly evaluate the
      diagnostic performance of contrast-enhanced ultrasonography (CEUS) versus
      contrast-enhanced computed tomography (CECT) for assessing residual tumors of
      hepatocellular carcinoma treated with transarterial chemoembolization. METHODS:
      PubMed, Embase, the Cochrane Library, and the China National Knowledge
      Infrastructure were searched through April 30, 2017. The pooled sensitivity,
      specificity, positive predictive value, negative predictive value, positive
      likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary
      receiver operating characteristic curve were calculated and compared to examine
      the diagnostic performance of CEUS versus CECT. RESULTS: A total of 11 studies,
      including 421 patients and 491 nodules were analyzed. The pooled diagnostic
      performances of CEUS versus CECT were as follows: (1) sensitivity (95% confidence
      interval), 0.97 (0.95-0.99) versus 0.72 (0.67-0.76); (2) specificity, 0.86 (0.74
      0.94) versus 0.99 (0.95-1.00); (3) positive predictive value, 0.97 (0.95-0.99)
      versus 1.00 (0.98-1.00); (4) negative predictive value, 0.90 (0.83-0.95) versus
      0.51 (0.44-0.58); (5) positive likelihood ratio, 7.79 (4.73-12.82) versus 12.50
      (5.74-27.20); (6) negative likelihood ratio, 0.05 (0.03-0.09) versus 0.35 (0.26
      0.48); (7) diagnostic odds ratio, 150.56 (57.03-397.49) versus 35.54 (14.89
      84.83); and (8) area under the summary receiver operating characteristic curve,
      0.9875 versus 0.9239. The sensitivity and negative predictive value of CEUS were
      significantly higher than those of CECT (both P < .001). The specificity and
      positive predictive value of CECT were significantly higher than those of CEUS
      (both P < .05). CONCLUSIONS: Contrast-enhanced US, with better sensitivity and
      negative predictive value versus CECT, was an effective method for exclusion of
      residual tumors after transarterial chemoembolization. Contrast-enhanced CT, with
      higher specificity than CEUS, is a valid approach for identifying residual
      tumors.

PMID- 29380405
TI  - The potential of radiolabeled chemotherapeutics in tumor diagnosis: Preliminary
      investigations with 68 Ga-gemcitabine.
AB  - Preclinical Research & Development Gemcitabine, a nucleoside analog, is a well
      known chemotherapeutic drug that is used either alone or with other agents to
      treat a wide variety of cancers. The aim of the present work was to evaluate the
      potential of 68 Ga-labeled gemcitabine for its application in positron emission
      tomography (PET) imaging of tumorous lesions. Gemcitabine was coupled with p-NCS
      benzyl-DOTA in order to facilitate radiolabeling with 68 Ga. The gemcitabine-p
      NCS-benzyl-DOTA was radiolabeled with 68 Ga, obtained from a 68 Ge/68 Ga
      radionuclide generator. The radiolabeled product was characterized by high
      performance liquid chromatography (HPLC) and its tumor specificity was evaluated
      by biodistribution studies in Swiss mice bearing fibrosarcoma tumors. Preliminary
      bioevaluation study showed good tumor uptake within 1 hr post-administration
      [2.5% Injected Activity (IA) per g of tumor] with rapid renal clearance (>90% IA)
      and a high tumor to muscle ratio. 68 Ga-gemcitabine may have potential as a PET
      agent for tumor imaging.

PMID- 29380406
TI  - Foveal vision power errors induced by spectacle lenses designed to correct
      peripheral refractive errors.
AB  - PURPOSE: Radial Refractive Gradient (RRG) spectacles are lenses specifically
      designed to minimize peripheral hyperopic defocus typically found in conventional
      spectacles. Our goals were: (1) to demonstrate a method to design such lenses;
      and (2) to quantify the exact foveal vision power errors induced by them.
      METHODS: The design procedure was based on a point-by-point sequential surface
      construction algorithm that designs a front aspheric surface (back surface is
      spherical) to achieve a given overall tangential focal length of the lens. A
      peripheral refraction model was built based on average peripheral refractive
      errors from a set of eyes. We designed four negative lenses with optical powers: 
      2.5, -5.0, -7.5 and -10.0 D, so that the tangential focal length of the lens
      matches the retinal conjugate surface. RESULTS: The lenses induce very small
      sagittal power errors in a wide range of off-axis field angles (30 degrees ),
      solving the problem of peripheral hyperopic defocus. However, such designs
      introduce non-negligible mean power errors (above 0.25 D from 7 degrees , 6.8
      degrees , 7.1 degrees  and 7.8 degrees  for the -2.5, -5.0, -7.5 and -10.0 D
      lenses, respectively) for foveal vision in a rotating eye. CONCLUSION: Our
      results show the unavoidable errors introduced by RRG spectacles when used for
      dynamic foveal vision. The described method offers valuable information towards
      determining the best trade-off between controlling power errors for peripheral
      and foveal vision.

PMID- 29380407
TI  - WHO Global Consultation on Public Health Intervention against Early Childhood
      Caries.
AB  - Early Childhood Caries (ECC) is prevalent around the world, but in particular the
      disease is growing rapidly in low- and middle-income countries in parallel with
      changing diet and lifestyles. In many countries, ECC is often left untreated, a
      condition which leads to pain and adversely affects general health, growth and
      development, and quality of life of children, their families and their
      communities. Importantly, ECC is also a global public health burden, medically,
      socially and economically. In many countries, a substantial number of children
      require general anaesthesia for the treatment of caries in their primary teeth
      (usually extractions), and this has considerable cost and social implications. A
      WHO Global Consultation with oral health experts on "Public Health Intervention
      against Early Childhood Caries" was held on 26-28 January 2016 in Bangkok
      (Thailand) to identify public health solutions and to highlight their
      applicability to low- and middle-income countries. After a 3-day consultation,
      participants agreed on specific recommendations for further action. National
      health authorities should develop strategies and implement interventions aimed at
      preventing and controlling ECC. These should align with existing international
      initiatives such as the Sixtieth World Health Assembly Resolution WHA 60.17 Oral
      health: action plan for promotion and integrated disease prevention, WHO
      Guideline on Sugars and WHO breastfeeding recommendation. ECC prevention and
      control interventions should be integrated into existing primary healthcare
      systems. WHO public health principles must be considered when tackling the effect
      of social determinants in ECC. Initiatives aimed at modifying behaviour should
      focus on families and communities. The involvement of communities in health
      promotion, and population-directed and individual fluoride administration for the
      prevention and control of ECC is essential. Surveillance and research, including
      cost-effectiveness studies, should be conducted to evaluate interventions aimed
      at preventing ECC in different population groups.

PMID- 29380408
TI  - Analysing the impact of myopia on the Stiles-Crawford effect of the first kind
      using a digital micromirror device.
AB  - PURPOSE: Photoreceptor light acceptance is closely tied to the Stiles-Crawford
      effect of the first kind (SCE-I). Whether the SCE-I plays a role in myopic
      development remains unclear although a reduction in directionality has been
      predicted for high myopia. The purpose of this study is to analyse the
      relationship between foveal SCE-I directionality, axial eye length, and defocus
      for emmetropic subjects wearing ophthalmic trial lenses during psychophysical
      measurements and for myopic subjects with their natural correction. METHOD: A
      novel uniaxial flicker system has been implemented making use of a Digital
      Micromirror Device (DMD) to flicker between a 2.3 visual degrees circular
      reference and a set of circular test patterns in a monocular Maxwellian view at
      0.5 Hz. The brightness of the test is adjusted by the duty cycle of the projected
      light to an upper limit of 22 727 Hz. The wavelength and bandwidth are set by a
      tuneable liquid-crystal filter centred at 550 nm. A total of four measurement
      series for 11 pupil entrance points have been realized for the right eye of 6
      emmetropic and 10 myopic subjects whose pupils were dilated with tropicamide.
      Five of the emmetropic subjects wore ophthalmic trial lenses in the range of -3
      to +9 dioptres to mimic hyperopic to highly myopic vision and resulting
      visibility plots have been fitted to a Gaussian SCE-I function. In turn, the
      myopic subjects wore their natural correction during the analysis of the SCE-I.
      All subjects had their axial eye length determined with an ultrasound device.
      RESULTS: A SCE-I directionality parameter in the range of 0.03 to 0.06/mm2 was
      found for the emmetropic subjects with corrected vision in fair agreement to
      values in the literature. The results also revealed a marked reduction in
      directionality in the range from 16% to 30% with every 3 dioptre increase of
      simulated myopia, as well as a 10% increased directionality in simulated
      hyperopic eyes. For both emmetropic and myopic subjects, a decrease in
      directionality with increase in axial length was found in agreement with
      theoretical expectations. CONCLUSION: The study confirms a clear link between SCE
      I directionality, uncorrected defocus, and axial eye length. This may play a role
      for emmetropization and thus myopic progression as cone photoreceptors capture
      light from a wider pupil area in elongated eyes due to a geometrical scaling.

PMID- 29380409
TI  - Morning surge in blood pressure using a random-effects multiple-component cosinor
      model.
AB  - Blood pressure (BP) fluctuates throughout the day. The pattern it follows
      represents one of the most important circadian rhythms in the human body. For
      example, morning BP surge has been suggested as a potential risk factor for
      cardiovascular events occurring in the morning, but the accurate quantification
      of this phenomenon remains a challenge. Here, we outline a novel method to
      quantify morning surge. We demonstrate how the most commonly used method to model
      24-hour BP, the single cosinor approach, can be extended to a multiple-component
      cosinor random-effects model. We outline how this model can be used to obtain a
      measure of morning BP surge by obtaining derivatives of the model fit. The model
      is compared with a functional principal component analysis that determines the
      main components of variability in the data. Data from the Mitchelstown Study, a
      population-based study of Irish adults (n = 2047), were used where a subsample
      (1207) underwent 24-hour ambulatory blood pressure monitoring. We demonstrate
      that our 2-component model provided a significant improvement in fit compared
      with a single model and a similar fit to a more complex model captured by b
      splines using functional principal component analysis. The estimate of the
      average maximum slope was 2.857 mmHg/30 min (bootstrap estimates; 95% CI: 2.855
      2.858 mmHg/30 min). Simulation results allowed us to quantify the between
      individual SD in maximum slopes, which was 1.02 mmHg/30 min. By obtaining
      derivatives we have demonstrated a novel approach to quantify morning BP surge
      and its variation between individuals. This is the first demonstration of cosinor
      approach to obtain a measure of morning surge.

PMID- 29380411
TI  - Electron microscopy of Drosophila garland cell nephrocytes: Optimal preparation,
      immunostaining and STEM tomography.
AB  - Due to its structural and molecular similarities to mammalian podocytes, the
      Drosophila nephrocyte emerged as a model system to study podocyte development and
      associated diseases. Similar to podocytes, nephrocytes establish a slit diaphragm
      between foot process-like structures in order to filter the hemolymph. One major
      obstacle in nephrocyte research is the distinct visualization of this subcellular
      structure to assess its integrity. Therefore, we developed a specialized
      dissection and fixation protocol, including high pressure freezing and freeze
      substitution techniques, to improve the preservation of the intricate
      ultrastructural details necessary for electron microscopic assessment. By means
      of scanning transmission electron microscopy (STEM) tomography, a three
      dimensional dataset was generated to further understand the complex architecture
      of the nephrocyte channel system. Moreover, a staining protocol for
      immunolabeling of ultrathin sections of Epon-embedded nephrocytes is discussed,
      which allows the reliable detection of GFP-tagged fusion proteins combined with
      superior sample preservation. Due to the growing number of available GFP-trap fly
      lines, this approach is widely applicable for high resolution localization
      studies in wild type and mutant nephrocytes.

PMID- 29380410
TI  - Ra-224 labeling of calcium carbonate microparticles for internal alpha-therapy:
      Preparation, stability, and biodistribution in mice.
AB  - Internal therapy with alpha-emitters should be well suited for micrometastatic
      disease. Radium-224 emits multiple alpha-particles through its decay and has a
      convenient 3.6 days of half-life. Despite its attractive properties, the use of
      224 Ra has been limited to bone-seeking applications because it cannot be stably
      bound to a targeting molecule. Alternative delivery systems for 224 Ra are
      therefore of considerable interest. In this study, calcium carbonate
      microparticles are proposed as carriers for 224 Ra, designed for local therapy of
      disseminated cancers in cavitary regions, such as peritoneal carcinomatosis.
      Calcium carbonate microparticles were radiolabeled by precipitation of 224 Ra on
      the particle surface, resulting in high labeling efficiencies for both 224 Ra and
      daughter 212 Pb and retention of more than 95% of these nuclides for up to 1 week
      in vitro. The biodistribution after intraperitoneal administration of the 224 Ra
      labeled CaCO3 microparticles in immunodeficient mice revealed that the
      radioactivity mainly remained in the peritoneal cavity. In addition, the systemic
      distribution of 224 Ra was found to be strongly dependent on the amount of
      administered microparticles, with a reduced skeletal uptake of 224 Ra with
      increasing dose. The results altogether suggest that the 224 Ra-labeled CaCO3
      microparticles have promising properties for use as a localized internal alpha
      therapy of cavitary cancers.

PMID- 29380412
TI  - From Drug Safety to Drug Security: A Contemporary Shift in the Policing of
      Health.
AB  - The counterfeiting of medication is increasingly seen as a major threat to
      health, especially in the light of both the everyday reliance on and a broadening
      of world-wide access to pharmaceuticals. Exaggerated or real, this threat has
      inaugurated, this article argues, a shift from a drug safety regime to a drug
      security regime that governs the flow of pharmaceuticals and brings together
      markets, police, and health actors in new ways. This entails a shift from soft
      disciplinary means aimed at incremental and continued inclusion of defaulters, to
      one of drastically sovereign measures of exclusion and banishment aimed at fake
      goods and the people associated with them, in the name of health. Through a multi
      sited ethnographic study, this article shows how such new drug security efforts
      play themselves out especially in (South) Africa, highlighting a modus operandi
      of spectacular performativity and of working through suspicion and association
      rather than factuality, producing value less so for those in need of health than
      for a petty security industry itself.

PMID- 29380413
TI  - Non-invasive assessments for liver fibrosis: The crystal ball we long for.
AB  - Non-invasive assessment of liver fibrosis has been one of the most rapidly
      advancing fields in hepatology in the last decade. Progressive liver fibrosis
      results in cirrhosis, hepatocellular carcinoma (HCC), and various liver-related
      complications in essentially all chronic liver diseases. Assessment of liver
      fibrosis allows clinicians to determine the prognosis, need of treatment, disease
      progression, and response to treatment in patients with chronic liver disease.
      Liver biopsy has been the gold standard in last few decades and most adopted
      diagnostic tool in clinical trials. Nonetheless, it is impractical to apply the
      test in a large number of patients or to do it serially. Hence, various non
      invasive assessments have been developed and adopted in some international
      management guidelines. Liver stiffness measurement (LSM) with transient
      elastography is one of the most widely validated non-invasive assessments for
      liver fibrosis. It is an accurate and reproducible method to predict advanced
      fibrosis in chronic hepatitis B. Using transient elastography, it is possible to
      perform repeated liver fibrosis assessments on a large number of asymptomatic
      patients. The key challenge of his tool is the confounding effect of alanine
      aminotransferase (ALT) level, such that decrease in LSM may only reflect ALT
      normalization, hence not accurate enough to indicate regression of liver
      fibrosis. This may be partially handled by combining LSM with a serum-based
      formula, which is independent of ALT such as the Forns index and enhanced liver
      fibrosis test. An LSM-based HCC risk score is useful to prioritize patients for
      HCC surveillance.

PMID- 29380414
TI  - Isotropic resolution diffusion tensor imaging of lumbosacral and sciatic nerves
      using a phase-corrected diffusion-prepared 3D turbo spin echo.
AB  - PURPOSE: To perform in vivo isotropic-resolution diffusion tensor imaging (DTI)
      of lumbosacral and sciatic nerves with a phase-navigated diffusion-prepared (DP)
      3D turbo spin echo (TSE) acquisition and modified reconstruction incorporating
      intershot phase-error correction and to investigate the improvement on image
      quality and diffusion quantification with the proposed phase correction. METHODS:
      Phase-navigated DP 3D TSE included magnitude stabilizers to minimize motion and
      eddy-current effects on the signal magnitude. Phase navigation of motion-induced
      phase errors was introduced before readout in 3D TSE. DTI of lower back nerves
      was performed in vivo using 3D TSE and single-shot echo planar imaging (ss-EPI)
      in 13 subjects. Diffusion data were phase-corrected per kz plane with respect to
      T2 -weighted data. The effects of motion-induced phase errors on DTI
      quantification was assessed for 3D TSE and compared with ss-EPI. RESULTS: Non
      phase-corrected 3D TSE resulted in artifacts in diffusion-weighted images and
      overestimated DTI parameters in the sciatic nerve (mean diffusivity [MD] = 2.06
      +/- 0.45). Phase correction of 3D TSE DTI data resulted in reductions in all DTI
      parameters (MD = 1.73 +/- 0.26) of statistical significance (P <= 0.001) and in
      closer agreement with ss-EPI DTI parameters (MD = 1.62 +/- 0.21). CONCLUSION: DP
      3D TSE with phase correction allows distortion-free isotropic diffusion imaging
      of lower back nerves with robustness to motion-induced artifacts and DTI
      quantification errors. Magn Reson Med 80:609-618, 2018. (c) 2018 The Authors
      Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of
      International Society for Magnetic Resonance in Medicine. This is an open access
      article under the terms of the Creative Commons Attribution NonCommercial
      License, which permits use, distribution and reproduction in any medium, provided
      the original work is properly cited and is not used for commercial purposes.

PMID- 29380415
TI  - Sofosbuvir plus ribavirin with or without peginterferon for the treatment of
      hepatitis C virus: Results from a phase 3b study in China.
AB  - BACKGROUND AND AIM: Sofosbuvir is a nucleotide analog inhibitor of the hepatitis
      C virus (HCV) NS5B RNA polymerase with pangenotypic potency. This phase 3b study
      evaluated the safety and efficacy of sofosbuvir + ribavirin +/- peginterferon in
      Chinese patients infected with HCV genotype 1, 2, 3, or 6. METHODS: Patients with
      genotype 1 or 6 received sofosbuvir + peginterferon/ribavirin for 12 weeks or
      sofosbuvir + ribavirin for 24 weeks, depending on prior treatment and interferon
      eligibility. Patients with genotype 2 or 3 received sofosbuvir + ribavirin for 12
      or 24 weeks, respectively. The primary endpoint was sustained virologic response
      at 12 weeks after the end of treatment (SVR12). RESULTS: Of 389 patients, 42% had
      genotype 1, 16% genotype 2, 32% genotype 3, and 9% genotype 6. Half were male,
      58% were treatment-naive, and 15% had cirrhosis. SVR12 rates for patients
      receiving 12 weeks of sofosbuvir + peginterferon/ribavirin were 94% (95%
      confidence interval [CI], 87-98%) for HCV genotype 1 and 97% (95% CI, 84-100%)
      for genotype 6. SVR12 rates for those receiving sofosbuvir + ribavirin for 24
      weeks were 95% (95% CI, 87-99%) for genotype 1, 100% (95% CI, 40-100%) for
      genotype 6, and 95% (95% CI, 90-98%) for genotype 3. For genotype 2 patients
      receiving sofosbuvir + ribavirin for 12 weeks, the SVR12 rate was 92% (95% CI, 83
      97%). Twenty patients (5%) relapsed. Ten (3%) experienced serious adverse events.
      Three (< 1%) discontinued treatment because of adverse events, of whom one died
      because of treatment-unrelated adverse events. CONCLUSIONS: Sofosbuvir-based
      regimens were highly effective and safe in Chinese patients with HCV genotype 1,
      2, 3, or 6, suggesting sofosbuvir could serve as the backbone for HCV treatment
      in China irrespective of genotype.

PMID- 29380417
TI  - Toward an integrative molecular approach to wildlife disease.
AB  - Pathogens pose serious threats to human health, agricultural investment, and
      biodiversity conservation through the emergence of zoonoses, spillover to
      domestic livestock, and epizootic outbreaks. As such, wildlife managers are often
      tasked with mitigating the negative effects of disease. Yet, parasites form a
      major component of biodiversity that often persist. This is due to logistical
      challenges of implementing management strategies and to insufficient
      understanding of host-parasite dynamics. We advocate for an inclusive
      understanding of molecular diversity in driving parasite infection and variable
      host disease states in wildlife systems. More specifically, we examine the roles
      of genetic, epigenetic, and commensal microbial variation in disease
      pathogenesis. These include mechanisms underlying parasite virulence and host
      resistance and tolerance, and the development, regulation, and parasite
      subversion of immune pathways, among other processes. Case studies of devil
      facial tumor disease in Tasmanian devils (Sarcophilus harrisii) and
      chytridiomycosis in globally distributed amphibians exemplify the broad range of
      questions that can be addressed by examining different facets of molecular
      diversity. For particularly complex systems, integrative molecular analyses
      present a promising frontier that can provide critical insights necessary to
      elucidate disease dynamics operating across scales. These insights enable more
      accurate risk assessment, reconstruction of transmission pathways, discernment of
      optimal intervention strategies, and development of more effective and
      ecologically sound treatments that minimize damage to the host population and
      environment. Such measures are crucial when mitigating threats posed by wildlife
      disease to humans, domestic animals, and species of conservation concern.

PMID- 29380416
TI  - Astrocytes expressing ALS-linked mutant FUS induce motor neuron death through
      release of tumor necrosis factor-alpha.
AB  - Mutations in fused in sarcoma (FUS) are linked to amyotrophic lateral sclerosis
      (ALS), a fatal neurodegenerative disease affecting both upper and lower motor
      neurons. While it is established that astrocytes contribute to the death of motor
      neurons in ALS, the specific contribution of mutant FUS (mutFUS) through
      astrocytes has not yet been studied. Here, we used primary astrocytes expressing
      a N-terminally GFP tagged R521G mutant or wild-type FUS (WTFUS) and show that
      mutFUS-expressing astrocytes undergo astrogliosis, damage co-cultured motor
      neurons via activation of an inflammatory response and produce conditioned medium
      (ACM) that is toxic to motor neurons in isolation. Time lapse imaging shows that
      motor neuron cultures exposed to mutFUS ACM, but not WTFUS ACM, undergo
      significant cell loss, which is preceded by progressive degeneration of neurites.
      We found that Tumor Necrosis Factor-Alpha (TNFalpha) is secreted into ACM of
      mutFUS-expressing astrocytes. Accordingly, mutFUS astrocyte-mediated motor neuron
      toxicity is blocked by targeting soluble TNFalpha with neutralizing antibodies.
      We also found that mutant astrocytes trigger changes to motor neuron AMPA
      receptors (AMPAR) that render them susceptible to excitotoxicity and AMPAR
      mediated cell death. Our data provide the first evidence of astrocytic
      involvement in FUS-ALS, identify TNFalpha as a mediator of this toxicity, and
      provide several potential therapeutic targets to protect motor neurons in FUS
      linked ALS.

PMID- 29380418
TI  - Spontaneous up-regulation of SIRT1 during osteogenesis contributes to stem cells'
      resistance to oxidative stress.
AB  - Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM
      MSCs) is a central event in bone formation. However, oxidative stress has a
      deleterious impact on BM-MSC osteogenesis. In this study, we hypothesized that
      oxidative stress influenced BM-MSC osteogenesis differently in the early or late
      stages, in which silent information regulator type 1 (SIRT1) played a critical
      role. A continuous exposure to sublethal concentrations of hydrogen peroxide (H2
      O2 ), ranging from 25 to 100 uM for 21 days, resulted in the complete inhibition
      of BM-MSC osteogenesis. We found that a 7-day treatment with H2 O2 inhibited the
      lineage commitment of BM-MSCs toward osteoblasts, as evidenced by a significant
      reduction of alkaline phosphatase activity (a typical marker for early
      osteogenesis). However, moderate oxidative stress did not affect late
      differentiated BM-MSCs, as there were comparable levels of matrix mineralization
      (a typical marker for late osteogenesis). In addition, we observed a spontaneous
      up-regulation of SIRT1 and intracellular antioxidant enzymes such as superoxide
      dismutase 2, catalase, and glutathione peroxidase 1, which accounted for the
      enhanced resistance to oxidative stress upon osteogenic differentiation.
      Activation of SIRT1 by resveratrol rescued the effect of H2 O2 on early
      differentiated BM-MSCs and inhibition of SIRT1 by nicotinamide intensified the
      effect of H2 O2 on late-differentiated BM-MSCs, indicating that the SIRT1
      mediated pathway was actively involved in MSC osteogenesis and antioxidant
      mechanisms. Our findings uncovered the relationship between SIRT1 and resistance
      to H2 O2 -induced oxidative stress during BM-MSC osteogenesis, which could
      provide a new strategy for protecting MSCs from extracellular oxidative stress.

PMID- 29380419
TI  - Astroglial major histocompatibility complex class I following immune activation
      leads to behavioral and neuropathological changes.
AB  - In the central nervous system, major histocompatibility complex class I (MHCI)
      molecules are mainly expressed in neurons, and neuronal MHCI have roles in
      synapse elimination and plasticity. However, the pathophysiological significance
      of astroglial MHCI remains unclear. We herein demonstrate that MHCI expression is
      up-regulated in astrocytes in the medial prefrontal cortex (mPFC) following
      systemic immune activation by an intraperitoneal injection of polyinosinic
      polycytidylic acid (polyI:C) or hydrodynamic interferon (IFN)-gamma gene delivery
      in male C57/BL6J mice. In cultured astrocytes, MHCI/H-2D largely co-localized
      with exosomes. To investigate the role of astroglial MHCI, H-2D, or sH-2D was
      expressed in the mPFC of male C57/BL6J mice using an adeno-associated virus
      vector under the control of a glial fibrillary acidic protein promoter. The
      expression of astroglial MHCI in the mPFC impaired sociability and recognition
      memory in mice. Regarding neuropathological changes, MHCI expression in
      astrocytes significantly activated microglial cells, decreased parvalbumin
      positive cell numbers, and reduced dendritic spine density in the mPFC. A
      treatment with GW4869 that impairs exosome synthesis ameliorated these behavioral
      and neuropathological changes. These results suggest that the overexpression of
      MHCI in astrocytes affects microglial proliferation as well as neuronal numbers
      and spine densities, thereby leading to social and cognitive deficits in mice,
      possibly via exosomes created by astrocytes.

PMID- 29380420
TI  - Bicuspidization of the morphological tricuspid aortic valve with ascending aorta
      replacement in a 5-year-old child.
AB  - Ascending aortic aneurysms are rare in children and may lead to aortic
      insufficiency, dissection, and/or rupture. We present a 5-year-old child
      diagnosed with an ascending aortic aneurysm and severe aortic insufficiency,
      successfully treated with ascending aortic replacement with an aortic valve
      repair using a bicuspidation technique.

PMID- 29380421
TI  - The long non-coding RNA H19 rs217727 polymorphism is associated with PE
      susceptibility.
AB  - H19 is an imprinted gene transcribing a long noncoding RNA which was previously
      reported to be involved in some diseases. However, the association between the
      H19 polymorphisms and Pre-eclampsia (PE) susceptibility has remained elusive.
      This study aimed to evaluate the association between three H19 haplotype SNPs
      (rs3741219, rs217727, and rs2107425) and the risk of PE. The present case control
      study consisted of 193 PE women and 201 controls. The H19 rs3741219 and rs217727
      polymorphisms were genotyped with PCR-RFLP (Polymerase chain reaction-restriction
      fragment length polymorphism) and the H19 rs2107425 polymorphism with ARMS-PCR
      (Amplification refractory mutation system) methods. The frequency of alleles and
      genotypes of H19 rs3741219 and rs2107425 polymorphisms did not differ between PE
      women and controls. The frequency of the H19 rs217727T allele was significantly
      higher in PE women (P < 0.0001). The H19 rs217727 polymorphism was associated
      with higher PE susceptibility in the Co-dominant (OR = 12.1, 95% CI = 5.7-24.5, P
      < 0.0001 for CT genotype and OR = 29.7, 95% CI = 12.9-68.1, P < 0.0001 for TT
      genotype), Dominant (OR = 15.1, 95% CI = 7.5-30.3, P = P < 0.0001), Recessive (OR
      = 4.5, 95% CI = 2.6-7.9, P = < 0.0001), and Over-dominant (OR = 2.1, 95% CI = 1.4
      3.1, P = 0.0006) models. Furthermore, the CCC, TCT, TCC, and CCT haplotypes of
      H19 rs3741219, rs217727, rs2107425 were associated with lower risk of PE;
      however, the CTC, TTC, and TTT haplotypes were associated with higher risk of PE.
      In conclusion, the present study found the relationship between H19 rs217727 but
      not rs3741219 and rs2107425 polymorphisms and PE susceptibility. In addition, the
      CTC, TTC, and TTT haplotypes were associated with the higher risk of PE.

PMID- 29380423
TI  - Improved tolerance to off-resonance in spectral-spatial EPI of hyperpolarized [1
      13 C]pyruvate and metabolites.
AB  - PURPOSE: For 13 C echo-planar imaging (EPI) with spectral-spatial excitation,
      main field inhomogeneity can result in reduced flip angle and spatial artifacts.
      A hybrid time-resolved pulse sequence, multi-echo spectral-spatial EPI, is
      proposed combining broader spectral-spatial passbands for greater off-resonance
      tolerance with a multi-echo acquisition to separate signals from potentially co
      excited resonances. METHODS: The performance of the imaging sequence and the
      reconstruction pipeline were evaluated for 1 H imaging using a series of
      increasingly dilute 1,4-dioxane solutions and for 13 C imaging using an ethylene
      glycol phantom. Hyperpolarized [1-13 C]pyruvate was administered to two healthy
      rats. Multi-echo data of the rat kidneys were acquired to test realistic cases of
      off-resonance. RESULTS: Analysis of separated images of water and 1,4-dioxane
      following multi-echo signal decomposition showed water-to-dioxane 1 H signal
      ratios that were in agreement with the independent measurements by 1 H
      spectroscopy for all four concentrations of 1,4-dioxane. The 13 C signal ratio of
      two co-excited resonances of ethylene glycol was accurately recovered after
      correction for the spectral profile of the redesigned spectral-spatial pulse. In
      vivo, successful separation of lactate and pyruvate-hydrate signals was achieved
      for all except the early time points during which signal variations exceeded the
      temporal resolution of the multi-echo acquisition. CONCLUSION: Improved tolerance
      to off-resonance in the new 13 C data acquisition pipeline was demonstrated in
      vitro and in vivo. Magn Reson Med 80:925-934, 2018. (c) 2018 International
      Society for Magnetic Resonance in Medicine.

PMID- 29380424
TI  - Mild phenotype of junctional epidermolysis bullosa with pyloric atresia due to a
      novel mutation of the ITGB4 gene.

PMID- 29380425
TI  - Case of bullous pemphigoid associated with teneligliptin accompanied by severe
      mucous membrane involvement.

PMID- 29380422
TI  - MicroRNA-31 is required for astrocyte specification.
AB  - Previously, we determined microRNA-31 (miR-31) is a noncoding tumor suppressive
      gene frequently deleted in glioblastoma (GBM); miR-31 suppresses tumor growth, in
      part, by limiting the activity of NF-kappaB. Herein, we expand our previous
      studies by characterizing the role of miR-31 during neural precursor cell (NPC)
      to astrocyte differentiation. We demonstrate that miR-31 expression and activity
      is suppressed in NPCs by stem cell factors such as Lin28, c-Myc, SOX2 and Oct4.
      However, during astrocytogenesis, miR-31 is induced by STAT3 and SMAD1/5/8, which
      mediate astrocyte differentiation. We determined miR-31 is required for terminal
      astrocyte differentiation, and that the loss of miR-31 impairs this process
      and/or prevents astrocyte maturation. We demonstrate that miR-31 promotes
      astrocyte development, in part, by reducing the levels of Lin28, a stem cell
      factor implicated in NPC renewal. These data suggest that miR-31 deletions may
      disrupt astrocyte development and/or homeostasis.

PMID- 29380426
TI  - Calcified mediastinal mass found during aortic valve replacement.

PMID- 29380427
TI  - Real-time correction of respiration-induced distortions in the human spinal cord
      using a 24-channel shim array.
AB  - PURPOSE: To reduce respiration-induced magnetic field distortions and the
      attendant image artifacts in echo-planar imaging (EPI) of the human spinal cord.
      METHODS: Using a custom-designed 24-channel shim array, shim updates were issued
      in real time based on a concurrently monitored respiratory trace and a pair of
      gradient echo (GRE) field maps acquired during an initial training phase. Proof
      of-concept application in GRE-EPI was conducted in 6 subjects. RESULTS: Over the
      thoracic spinal cord, real-time shimming reduced respiration-induced distortions
      in the EPI by 48.2% +/- 12.2% and increased the mean temporal signal-to-noise
      ratio by 15.7% +/- 7.9%. CONCLUSION: Real-time shim adjustment substantially
      reduces spatiotemporal B0 field variation, opening the door to more robust
      imaging and spectroscopy investigations of the spinal cord. Magn Reson Med 80:935
      946, 2018. (c) 2018 International Society for Magnetic Resonance in Medicine.

PMID- 29380428
TI  - Impact of glucose and lipid markers on the correlation of calculated and
      enzymatic measured low-density lipoprotein cholesterol in diabetic patients with
      coronary artery disease.
AB  - BACKGROUND AND AIMS: Low-density lipoprotein cholesterol (LDL-C) is widely
      estimated by Friedewald equation (FE) and Enzymatic test (ET), which are affected
      by several factors. The aim of this study was to observe the impact of diabetic
      lipid and glucose patterns on the correlation between FE LDL-C (F-LDL) and ET LDL
      C (E-LDL) in patients with coronary artery disease (CAD). METHODS AND RESULTS: A
      total of 8155 CAD patients were consecutively enrolled and their lipid profiles
      were measured. The impacts of triglyceride (TG), glycosylated hemoglobin A1c
      (HbA1c), and high-density lipoprotein cholesterol (HDL-C) on the correlation of F
      LDL and E-LDL were examined. The difference value (DV) between F-LDL and E-LDL
      was compared using ANOVA test. The CAD patients with DM were elder and had higher
      body mass index, plasma TG compared with those without DM (P < .05 separately).
      In the whole population, F-LDL was lower than E-LDL but showed a high correlation
      with E-LDL (r = .970, P = .000). Moreover, as the TG concentrations increased,
      the DV increased accordingly but the correlation between F-LDL and E-LDL
      decreased (P < .01). The similar trend was also found in both DM and non-DM
      patients comparing with different TG groups. However, in patients with DM, there
      was no significant difference of DV in different HbA1c groups or HDL-C
      concentrations (P > .05). CONCLUSION: Although F-LDL might underestimate the
      value of LDL-C, the correlation between F-LDL and E-LDL was clinically acceptable
      (r = .97), suggesting the LDL-C values measured by two methods were similarly
      reliable in CAD patients with or without DM.

PMID- 29380429
TI  - The strength of weight-bearing bones is similar in amenorrheic and eumenorrheic
      elite long-distance runners.
AB  - Regular intense endurance exercise can lead to amenorrhea with possible adverse
      consequences for bone health. We compared whole body and regional bone strength
      and skeletal muscle characteristics between amenorrheic (AA: n = 14) and
      eumenorrheic (EA: n = 15) elite adult female long-distance runners and
      nonathletic controls (C: n = 15). Participants completed 3-day food diaries, dual
      energy X-ray absorptiometry (DXA), magnetic resonance imaging (MRI), peripheral
      quantitative computed tomography (pQCT), and isometric maximal voluntary knee
      extension contraction (MVC). Both athlete groups had a higher caloric intake than
      controls, with no significant difference between athlete groups. DXA revealed
      lower bone mineral density (BMD) at the trunk, rib, pelvis, and lumbar spine in
      the AA than EA and C. pQCT showed greater bone size in the radius and tibia in EA
      and AA than C. The radius and tibia of AA had a larger endocortical circumference
      than C. Tibia bone mass and moments of inertia (Ix and Iy) were greater in AA and
      EA than C, whereas in the radius, only the proximal Iy was larger in EA than C.
      Knee extensor MVC did not differ significantly between groups. Amenorrheic adult
      female elite long-distance runners had lower BMD in the trunk, lumbar spine,
      ribs, and pelvis than eumenorrheic athletes and controls. The radius and tibia
      bone size and strength indicators were similar in amenorrheic and eumenorrheic
      athletes, suggesting that long bones of the limbs differ in their response to
      amenorrhea from bones in the trunk.

PMID- 29380430
TI  - Material Design of p-Type Transparent Amorphous Semiconductor, Cu-Sn-I.
AB  - Transparent amorphous semiconductors (TAS) that can be fabricated at low
      temperature are key materials in the practical application of transparent
      flexible electronics. Although various n-type TAS materials with excellent
      performance, such as amorphous In-Ga-Zn-O (a-IGZO), are already known, no
      complementary p-type TAS has been realized to date. Here, a material design
      concept for p-type TAS materials is proposed utilizing the pseudo s-orbital
      nature of spatially spreading iodine 5p orbitals and amorphous Sn-containing CuI
      (a-CuSnI) thin film is reported as an example. The resulting a-CuSnI thin films
      fabricated by spin coating at low temperature (140  degrees C) have a smooth
      surface. The Hall mobility increases with the hole concentration and the largest
      mobility of ~9 cm2 V-1 s-1 is obtained, which is comparable with that of
      conventional n-type TAS.

PMID- 29380431
TI  - Mesoscale Block Copolymers.
AB  - Materials composed of well-defined mesoscale building blocks are ubiquitous in
      nature, with noted ability to assemble into hierarchical structures possessing
      exceptional physical and mechanical properties. Fabrication of similar synthetic
      mesoscale structures will offer opportunities for precise conformational tuning
      toward advantageous bulk properties, such as increased toughness or elastic
      modulus. This requires new materials designs to be discovered to impart such
      structural control. Here, the preparation of mesoscale polymers is achieved by
      solution fabrication of functional polymers containing photoinduced chemical
      triggers. Subsequent photopatterning affords mesoscale block copolymers composed
      of distinct segments of alternating chemical composition. When dispersed in
      appropriate solvents, selected segments form helices to generate architectures
      resembling block copolymers, but on an optically observable size scale. This
      approach provides a platform for producing mesoscale geometries with structural
      control and potential for driving materials assembly comparable to examples found
      in nature.

PMID- 29380432
TI  - High Detectivity and Transparent Few-Layer MoS2 /Glassy-Graphene Heterostructure
      Photodetectors.
AB  - Layered van der Waals heterostructures have attracted considerable attention
      recently, due to their unique properties both inherited from individual two
      dimensional (2D) components and imparted from their interactions. Here, a novel
      few-layer MoS2 /glassy-graphene heterostructure, synthesized by a layer-by-layer
      transfer technique, and its application as transparent photodetectors are
      reported for the first time. Instead of a traditional Schottky junction, coherent
      ohmic contact is formed at the interface between the MoS2 and the glassy-graphene
      nanosheets. The device exhibits pronounced wavelength selectivity as illuminated
      by monochromatic lights. A responsivity of 12.3 mA W-1 and detectivity of 1.8 *
      1010 Jones are obtained from the photodetector under 532 nm light illumination.
      Density functional theory calculations reveal the impact of specific carbon
      atomic arrangement in the glassy-graphene on the electronic band structure. It is
      demonstrated that the band alignment of the layered heterostructures can be
      manipulated by lattice engineering of 2D nanosheets to enhance optoelectronic
      performance.

PMID- 29380433
TI  - A note on a precursor of behavioral momentum.
AB  - This is a historical note on a precursor of the concept of behavioral momentum in
      the late 1950s and early 1960s, in particular, Charles B. description of it in
      terms of behavioral durability. The note is based largely on two email exchanges
      we had with John A. (Tony) Nevin, who offered insights on behavioral momentum as
      a term and a concept that are fit to be public on the occasion of this issue of
      the Journal of the Experimental Analysis of Behavior in his honor. Nevin
      addressed graduate work at Columbia University, the Newtonian analogy, the term
      behavioral momentum, and precursors of his work that are now lost in history.
      Ferster's description, though, was more compellingly modern than the others and
      the one first based in research on human operant behavior.

PMID- 29380435
TI  - Nevin's momentum.

PMID- 29380434
TI  - Persistence and relapse of reinforced behavioral variability.
AB  - The present study examined persistence and relapse of reinforced behavioral
      variability in pigeons. Pigeons emitted four-response sequences across two keys.
      Sequences produced food according to a lag schedule, in which a response sequence
      was followed by food if it differed from a certain number of previous sequences.
      In Experiment 1, food was delivered for sequences that satisfied a lag schedule
      in both components of a multiple schedule. When reinforcement was removed for one
      component (i.e., extinction), levels of behavioral variability decreased for only
      that component. In Experiment 2, food was delivered for sequences satisfying a
      lag schedule in one component of a multiple schedule. In the other component,
      food was delivered at the same rate, but without the lag variability requirement
      (i.e., yoked). Following extinction, levels of behavioral variability returned to
      baseline for both components after response-independent food delivery (i.e.,
      reinstatement). In Experiment 3, one group of pigeons responded on a lag
      variability schedule, and the other group responded on a lag repetition schedule.
      For both groups, levels of behavioral variability increased when alternative
      reinforcement was suspended (i.e., resurgence). In each experiment, we observed
      some evidence for extinction-induced response variability and for variability as
      an operant dimension of behavior.

PMID- 29380436
TI  - Additional free reinforcers increase persistence of problem behavior in a
      clinical context: A partial replication of laboratory findings.
AB  - Behavioral momentum theory is a quantitative framework used to characterize the
      persistence of behavior during response disruptors as a function of baseline
      stimulus-reinforcer relations. Results of several investigations have shown that
      alternative reinforcement can increase the resistance to change of a target
      response during extinction. In the present study, concomitant variable-interval
      fixed-time schedules of reinforcement for problem behavior were employed to
      simulate naturalistic situations involving the superimposition of response
      independent reinforcers on a baseline schedule of reinforcement for problem
      behavior, as in the common use of noncontingent reinforcement treatments.
      Resistance to change of problem behavior was assessed during postsession periods
      of extinction by comparing response rates in extinction following sessions with
      and without additional reinforcer deliveries arranged by fixed-time schedules.
      For 2 out of 3 participants, problem behavior tended to be more resistant to
      extinction following periods in which additional fixed-time reinforcers were
      delivered. These results are discussed in terms of potential effects of
      noncontingent reinforcement on problem behavior when the intervention is
      discontinued or implemented without good treatment integrity.

PMID- 29380437
TI  - On the predictive validity of behavioral momentum theory for mitigating
      resurgence of problem behavior.
AB  - We summarize the results of four recent translational studies from our lab that
      used the predictions of behavioral momentum theory to inform the development of
      more durable treatments for destructive behavior. Treatments informed by
      behavioral momentum theory generally showed better suppression of target
      responding during an extinction challenge than did a comparison treatment. We
      reanalyze data from each of the four studies to show that this general finding is
      apparent both at the aggregate (i.e., proportion of baseline response rates
      averaged across participants) and within participant (i.e., percentage reduction
      in proportion of baseline response rates, difference in raw response rates during
      the extinction challenge). Interestingly, participants who experienced multiple
      cycles of the extinction challenge generally showed less differentiation in
      target responding between the treatment informed by behavioral momentum theory
      and the comparison treatment. Overall results suggest that applications of
      behavioral momentum theory can substantially improve the durability of common
      treatments for destructive behavior.

PMID- 29380438
TI  - Homeobox transcription factor DLX4 is not necessary for skin development and
      homeostasis.
AB  - Dlx4 is a member of a family of homeobox genes with homology to Drosophila distal
      less (dll) gene. We show that Dlx4 expression pattern partially overlaps with its
      cis-linked gene Dlx3 during mouse development as well as in neonatal and adult
      skin. In mice, Dlx4 is expressed in the branchial arches, embryonic limbs,
      digits, nose, hair follicle and in the basal and suprabasal layers of mouse
      interfollicular epidermis. We show that inactivation of Dlx4 in mice did not
      result in any overtly gross pathology. Skin development, homeostasis and response
      to TPA treatment were similar in mice with loss of Dlx4 compared to wild-type
      counterparts.

PMID- 29380439
TI  - Precise Molecular Sieving Architectures with Janus Pathways for Both Polar and
      Nonpolar Molecules.
AB  - Precise molecular sieving architectures with Janus superhighways are constructed
      via a molecularly engineered interfacial reaction between cyclodextrin (CD) and
      trimesoyl chloride (TMC). Interestingly, the CD/TMC nanofilms constructed with
      both hydrophobic inner cavities and hydrophilic channels exhibit exceptionally
      high permeances for both polar and nonpolar solvents. The precise molecular
      sieving functions are determined by the type of CD building blocks and the inner
      cavities of intrinsic 3D hollow bowls. Positron annihilation spectroscopy (PAS)
      confirms that a larger inner CD cavity tends to generate a larger free volume and
      higher microporosity. Based on the rejection ratio of various dyes, the estimated
      molecular weight cutoff of CD/TMC nanofilms follows the trend of alpha-CD/TMC
      (320 Da) <beta-CD/TMC (400 Da) <gamma-CD/TMC (550 Da), which is in strict
      accordance with the orders of their free volumes measured by PAS and inner cavity
      sizes of alpha-CD <beta-CD <gamma-CD. This kind of novel CD/TMC molecular sieving
      membrane with intrinsic microporosity containing tunable pore size and sharp pore
      size distribution can effectively discriminate molecules with different 3D sizes.

PMID- 29380440
TI  - miRNA-15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 expressions in
      autologous hematopoietic stem cell transplantation and their impact on
      engraftment.
AB  - OBJECTIVE: MicroRNAs engaged in angiogenesis and hematopoiesis can influence
      hematopoietic stem cells (HSCs) homing after transplantation by targeting bone
      marrow niche microenvironment. This study aimed to examine the kinetics of miRNA
      15a, miRNA-16, miRNA-126, miRNA-146a, and miRNA-223 in autologous HSC
      transplantation settings. METHODS: The study comprised of 51 patients with
      hematological malignancies (42 multiple myeloma, 9 lymphoma). Samples were taken
      at four time points: before conditioning, after chemotherapy but prior to
      autologous HSC transplantation (day 0), on day +7, and +14 days after HSCT. The
      miRNA levels were evaluated by the real-time PCR method. RESULTS: A significant,
      steady decline of all tested microRNAs in the course of transplantation, as
      compared to the baseline, was found. The study revealed that higher levels of
      miRNA-15a, miRNA-16, miRNA-126, and miRNA-146a on day 0 correlated with longer
      time to engraftment. Additionally, a positive correlation between the levels of
      miRNA-15a, miRNA-146a, and miRNA-223 assessed on day +7 and the time to
      engraftment was observed. CONCLUSIONS: In conclusion, all investigated microRNAs
      changed significantly in the course of transplantation. Our results suggest that
      the miRNAs may participate in hematopoietic recovery in the early post-transplant
      period and influence engraftment efficiency after HSCT.

PMID- 29380441
TI  - Deregulation of microRNA-155 and its transcription factor NF-kB by
      polychlorinated biphenyls during viral infections.
AB  - Polychlorinated biphenyls (PCBs), and similar environmental contaminants, have
      been linked to virus outbreaks and increased viral induced mortality since the
      1970s. Yet the mechanisms behind this increased susceptibility remain elusive. It
      has recently been illustrated that the innate immune viral detection system is
      tightly regulated by small non-coding RNAs, including microRNAs (miRNAs). For
      virus infections miRNA-155 expression is an important host response against
      infection, and deregulation of this miRNA is closely associated with adverse
      outcomes. Thus, we designed a targeted in vitro study using primary chicken
      fibroblasts, first exposed to a mixture of PCBs (Arochlor-1250) before being
      stimulated with a synthetic RNA virus (poly I:C), to determine if PCBs have the
      potential to deregulate miRNA-155. In this paper, we provide the first data for
      the deregulation of miRNA-155 when a host is exposed to a mixture of PCBs before
      a virus infection. Thus, we provide important evidence that PCBs can be involved
      in the deregulation of important miRNA pathways involved in the immune system;
      thereby demonstrating novel insights into the mechanism of PCB toxicity on the
      immune system.

PMID- 29380443
TI  - A topical treatment containing heat-treated Lactobacillus johnsonii NCC 533
      reduces Staphylococcus aureus adhesion and induces antimicrobial peptide
      expression in an in vitro reconstructed human epidermis model.
AB  - Staphylococcus aureus colonization is thought to contribute to the
      pathophysiology of atopic dermatitis (AD). AD patients exhibit reduced levels of
      cutaneous antimicrobial peptides (AMPs), which may explain their increased
      susceptibility to infections. Using an in vitro reconstructed human epidermis
      (RHE) model, we sought to determine whether topical application of a non
      replicating probiotic, heat-treated Lactobacillus johnsonii NCC 533 (HT La1),
      could inhibit S. aureus adhesion to skin and boost cutaneous innate immunity. We
      found that application of HT La1 suspension to RHE samples reduced the binding of
      radiolabelled S. aureus by up to 74%. To investigate a potential effect of HT La1
      on innate immunity, we analysed the expression of nine AMP genes, including those
      encoding beta defensins and S100 proteins, following topical application of HT
      La1 in suspension or in a daily moisturizer lotion. Analysed genes were induced
      by up to fourfold in a dose-dependent manner by HT La1 in suspension and by up to
      2.4-fold by HT La1 in the moisturizer lotion. Finally, using ELISA and
      immunohistochemical detection, we evaluated the expression and secretion of the
      AMPs hBD-2 and psoriasin and determined that both proteins were induced by
      topical HT La1, particularly in the stratum corneum of the RHE. These findings
      demonstrate that a topically applied, non-replicating probiotic can modulate
      endogenous AMP expression and inhibit binding of S. aureus to an RHE model in
      vitro. Moreover, they suggest that a topical formulation containing HT La1 could
      benefit atopic skin by enhancing cutaneous innate immunity and reducing S. aureus
      colonization.

PMID- 29380442
TI  - Locoregional treatments before liver transplantation for hepatocellular
      carcinoma: a study from the European Liver Transplant Registry.
AB  - Locoregional treatment while on the waiting list for liver transplantation (Ltx)
      for hepatocellular carcinoma (HCC) has been shown to improve survival. However,
      the effect of treatment type has not been investigated. We investigate the effect
      of locoregional treatment type on survival after Ltx for HCC. We investigated
      patients registered in the European Liver Transplant Registry database using
      multivariate Cox regression survival analysis. Information on locoregional
      therapy was registered for 4978 of 23 124 patients and was associated with
      improved overall survival [hazard ratio (HR) 0.84 (0.73-0.96)] and HCC-specific
      survival [HR 0.76 (0.59-0.98)]. Radiofrequency ablation (RFA) was the one
      monotherapy associated with improved overall survival [HR 0.51 (0.40-0.65)]. In
      addition, the combination of RFA and transarterial chemoembolization also
      improved survival [HR 0.74 (0.55-0.99)]. Adjusting for factors related to
      prognosis, disease severity, and tumor aggressiveness, RFA was highly beneficial
      for overall and HCC-specific survival. The effect may represent a selection of
      patients with favorable tumor biology; however, the treatment may be effective
      per se by halting tumor progression. Clinicaltrials.gov number: NCT02995096.

PMID- 29380444
TI  - Performance of existing risk scores around heart transplantation: validation
      study in a 4-year cohort.
AB  - Several risk scores exist to help identify best candidate recipients for heart
      transplantation (HTx). This study describes the performance of five heart failure
      risk scores and two post-HTx mortality risk scores in a French single-centre
      cohort. All patients listed for HTx through a 4-year period were included.
      Waiting-list risk scores [Heart Failure Survival Score (HFSS), Seattle Heart
      Failure Model (SHFM), Meta-Analysis Global Group in Chronic Heart Failure
      (MAGGIC), Organized Program to Initiate Lifesaving Treatment in Hospitalized
      Patients with Heart Failure (OPTIMIZE-HF) and Get With The Guidelines-Heart
      Failure (GWTG-HF)] and post-HTx scores Index for Mortality Prediction After
      Cardiac Transplantation (IMPACT and CARRS) were computed. Main outcomes were 1
      year mortality on waiting list and after HTx. Performance was assessed using
      receiver operator characteristic (ROC), calibration and goodness-of-fit analyses.
      The cohort included 414 patients. Waiting-list mortality was 14.0%, and post-HTx
      mortality was 16.3% at 1-year follow-up. Heart failure risk scores had adequate
      discrimination regarding waiting-list mortality (ROC AUC for HFSS = 0.68, SHFM =
      0.74, OPTIMIZE-HF = 0.72, MAGGIC = 0.70 and GWTG = 0.77; all P-values <0.05). On
      the contrary, post-HTx risk scores did not discriminate post-HTx mortality (AUC
      for IMPACT = 0.58, and CARRS = 0.48, both P-values >0.50). Subgroup analysis on
      patients undergoing HTx after ventricular assistance device (VAD) implantation
      (i.e. bridge-to-transplantation) (n = 36) showed an IMPACT AUC = 0.72 (P <
      0.001). In this single-centre cohort, existing heart failure risk scores were
      adequate to predict waiting-list mortality. Post-HTx mortality risk scores were
      not, except in the VAD subgroup.

PMID- 29380445
TI  - Self-reported non-adherence to immunosuppressive medication in adult lung
      transplant recipients-A single-center cross-sectional study.
AB  - BACKGROUND: Non-adherence to immunosuppressive treatment following solid organ
      transplantation is common and often associated with poorer outcomes. Non
      adherence is difficult to assess, and barriers to adherence in lung transplant
      (LTx) recipients remain to be elucidated. METHODS: A single-center cross
      sectional observational study of all LTx recipients attending our department
      between 07/2013 and 05/2014 was performed. Non-adherence was assessed using
      patient self-reporting, including Basel Assessment of Adherence with
      Immunosuppressive Medication Scale (BAASIS) along with healthcare worker (HCW)
      judgment and reasons for non-adherence by the Immunosuppressive Therapy Barriers
      Scale. RESULTS: A total of 138/504 patients (27.4%) self-reported non-adherence
      to immunosuppressive medication. HCW scored 96/504 patients (19.1%) as poorly
      adherent. Self-reported non-adherence increased with increasing interval after
      transplantation. The main reason for non-adherence was punctuality (75%), with
      only 11% reporting drug holidays. Explanations for non-adherence were primarily
      related to self-organization and difficulties incorporating medication into daily
      routine. There were no significant differences in medication knowledge or
      variation in trough levels. CONCLUSIONS: This study confirms that non-adherence
      in LTx recipients is frequent according to self-report. Barriers are self
      organization and difficulties incorporating medication into daily routine. Social
      and behavioral support is needed to overcome non-adherence. (ClinicalTrials.gov
      number: NCT01889017).

PMID- 29380447
TI  - Differential impact of CX3CL1 on lung cancer prognosis in smokers and non
      smokers.
AB  - CX3CL1 is a unique chemokine, expressed in both soluble and membrane bound forms,
      which mediates different biological activities. Recent studies have revealed the
      potential of CX3CL1 signaling pathway as a target for the treatment of
      inflammation and cancer. The correlation between expression of CX3CL1 and
      prognosis of patients varies among cancers. In this study, based on CX3CL1
      immunohistochemistry in non-small cell lung cancer, CX3CL1 levels were positively
      associated with cancer stage (Pearson chi-square, P = 0.048) and lymph node
      status (P = 0.033). Interestingly, survival effects of CX3CL1 were only observed
      in patients with smoking history and adenocarcinoma (AD, log rank, P = 0.027),
      but not in patients with squamous cell carcinoma (SQ). The median survival time
      of patients with smoking history and low level CX3CL1 expressing AD was 1538
      days, while that of patients with smoking history and high level CX3CL1
      expressing AD was 396 days. Cox regression models showed adverse effects of high
      CX3CL1 levels only in AD patients with smoking history (hazard ratio = 3.01, p =
      0.034), but not in AD patients without smoking history or in SQ patients with
      smoking history. The results of this study suggest that CX3CL1 plays different
      roles in lung tumorigenesis in smokers and non-smokers, and different CX3CL1
      based therapeutic strategies are needed depending on patient smoking status and
      tumor type. Furthermore, high level of CX3CL1 expression enhances nodal
      metastasis by activating JNK & MMP2/MMP9 activity in lung cancer cells.

PMID- 29380446
TI  - SH2B1 promotes epithelial-mesenchymal transition through the IRS1/beta-catenin
      signaling axis in lung adenocarcinoma.
AB  - Lung adenocarcinoma (LADC), the most prevalent type of human lung cancer, is
      characterized by many molecular abnormalities. SH2B1, a member of the SH2-domain
      containing family, have recently been shown to act as tumor activators in
      multiple cancers, including LADC. However, the mechanisms underlying SH2B1
      overexpression are not completely understood. Here, we reported that SH2B1
      expression levels were significantly upregulated and positively associated with
      EMT markers and poor patient survival in LADC specimens. Modulation of SH2B1
      levels had distinct effects on cell proliferation, cell cycle, migration,
      invasion, and morphology in A549 and H1299 cells in vitro and in vivo. At the
      molecular level, overexpression of SH2B1 resulted in the upregulation of the EMT
      markers, especially induced beta-catenin accumulation and activated beta-catenin
      signaling to promote LADC cell proliferation and metastasis, while silencing
      SH2B1 had the opposite effect. Furthermore, ectopic expression of SH2B1 in H1299
      cells increased IRS1 expression level. Reduced expression of IRS1 considerably
      inhibited H1299 cell proliferation, migration, and invasion which were driven by
      SH2B1 overexpression. Collectively, these results provide unequivocal evidence to
      establish that SH2B1-IRS1-beta-catenin axis is required for promoting EMT, and
      might prove to be a promising strategy for restraining tumor progression in LADC
      patients.

PMID- 29380448
TI  - Longitudinal Assessment of Denture Maintenance Needs in an Overdenture
      Population.
AB  - PURPOSE: To evaluate the longitudinal denture maintenance needs of a tooth
      supported overdenture population. MATERIALS AND METHODS: This prospective cohort
      study was composed of patients who had received tooth-supported overdentures from
      1974 to 1994 in the Department of Prosthodontics, University of Iowa. There were
      272 persons with 662 abutments who fulfilled the inclusion criteria. To simplify
      analysis and reduce the number of confounding variables, only those participants
      wearing complete maxillary dentures and opposing complete mandibular overdentures
      supported by teeth #22 and #27 were included in this analysis. The denture
      maintenance needs of these participants were identified and related to age,
      gender, length of time wearing overdentures, number of medications, and denture
      wearing habits. Descriptive statistics and bivariate analyses were used for the
      statistical analysis (alpha = 0.05). RESULTS: Of the 91 participants (mean age =
      59.5 +/- 10.1 years; 63.7% male) who fulfilled the inclusion criteria at
      baseline, 48.4% took 1 to 3 medications daily, and 84.6% wore their dentures day
      and night. The percentages of participants who needed one or more of the
      following denture treatments were: 91.2% denture base adjustments, 76.9%
      laboratory processed relines, 61.5% denture remakes, 33% laboratory remount and
      occlusal adjustment, 22% repaired bases, and 19.8% needed denture teeth replaced.
      Bivariate analyses indicated that participants who were 65 years and older needed
      more denture adjustments than patients younger than 65 years (p = 0.0343).
      Participants who had worn overdentures for more than 5 years were more likely to
      require denture remakes (p = 0.0304). Participants who wore their dentures only
      during the day were less likely to require repairs (p = 0.0403). Participants who
      did not take any medications were significantly less likely to require denture
      base repairs (p = 0.0258). For the 35 participants who returned for recalls at
      all 4 time points, males were more likely to need denture teeth repaired or
      replaced (p = 0.0335) and those aged 50 to 64 were more likely to need 2 or more
      adjustments (p = 0.0311). No overdenture abutments were lost by the participants
      in this study. CONCLUSIONS: According to the results of this study, age,
      medication usage, denture-wearing habits, and age of the overdentures were
      significant factors associated with denture maintenance needs. Persons wearing
      overdentures need regular recalls, because they have continuing maintenance
      needs.

PMID- 29380449
TI  - A self-caricature of michelangelo buonarroti hidden in the portrait of vittoria
      colonna.
AB  - The specialized literature has described how the great anatomist par excellence,
      Michelangelo Buonarroti (1475-1564), like many other renowned artists of his
      time, included a self-portrait in many of his works. This article presents novel
      evidence that Michelangelo inserted his self-portrait into a sketch of his close
      friend, Vittoria Colonna (1490-1547). This work, made by Michelangelo in 1525, is
      currently in the collection of the British Museum in London, England. This self
      portrait of Michelangelo can serve as a tool for analyzing the artist's probable
      bodily dimensions and even his state of health during this period of his life.
      Clin. Anat. 31:335-338, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29380450
TI  - Fibrillization of beta-Amyloid Peptides via Chemically Modulated Pathway.
AB  - The aggregation of beta-amyloid peptides is closely associated with Alzheimer's
      disease. We have used liposomes to modulate the early aggregation events of 40
      residue beta-amyloid peptides. The spatial confinement provided by liposomes
      leads to the formation of nonfibrillar aggregates of beta-amyloid peptides. These
      on-pathway beta-sheet intermediates were used to seed the fibrillization of the
      monomer peptides. Solid-state NMR spectroscopy revealed that the resultant
      fibrils have a more uniform structure than those formed in liposome-free
      solution.

PMID- 29380451
TI  - Human T-lymphotropic virus type 1 infection and solid organ transplantation.
AB  - HTLV infection appears to be more common among renal transplant candidates than
      in the related general population. HTLV-1-associated diseases may occur in
      carriers who are transplanted but there is insufficient evidence to confirm
      whether these occur more frequently as a result of the associated
      immunosuppression. Consequently, pre-existing HTLV-1 infection should not be
      considered a contra-indication to transplantation. The risk of transmission of
      HTLV-1 through solid organ transplantation from a confirmed infected donor is
      unknown. There are anecdotes of multiple infections from a single donor.
      Biologically due to the significant volume of blood and the lack of storage,
      transmission would be expected to be higher than following blood transfusion. The
      rate of subsequent disease is unknown, but there are now 11 reports of HAM and 2
      of ATL occurring within 4 years of transplantation associated infection. There
      are insufficient data to know whether the time from infection to onset of disease
      and the rate of progression differ from transmission through other routes, but
      early onset and rapid progression is a concern. Responses to enhanced
      immunosuppression for the treatment of HAM are variable. The risk of HTLV-1
      associated disease in exchange for a life-saving major organ transplantation from
      an infected donor might be considered worth taking by some HTLV-1 uninfected
      patients. Peri-transplantation antiretroviral prophylaxis with zidovudine and
      raltegravir is biologically sound but therapeutically unproven. The risks related
      to HTLV-1 infection appear to preclude the use of any other tissue. All
      transplant donors should be screened for HTLV-1 infection regardless of perceived
      risk.

PMID- 29380453
TI  - When neuroscience met clinical pathology: partitioning experimental variation to
      aid data interpretation in neuroscience.
AB  - In animal experiments, neuroscientists typically assess the effectiveness of
      interventions by comparing the average response of groups of treated and
      untreated animals. While providing useful insights, focusing only on group
      effects risks overemphasis of small, statistically significant but
      physiologically unimportant, differences. Such differences can be created by
      analytical variability or physiological within-individual variation, especially
      if the number of animals in each group is small enough that one or two outlier
      values can have considerable impact on the summary measures for the group.
      Physicians face a similar dilemma when comparing two results from the same
      patient. To determine whether the change between two values reflects disease
      progression or known analytical and physiological variation, the magnitude of the
      difference between two results is compared to the reference change value. These
      values are generated by quantifying analytical and within-individual variation,
      and differences between two results from the same patient are considered
      clinically meaningful only if they exceed the combined effect of these two
      sources of 'noise'. In this article, we describe how the reference change
      interval can be applied within neuroscience. This form of analysis provides a
      measure of outcome at an individual level that complements traditional group
      level comparisons, and therefore, introduction of this technique into
      neuroscience can enrich interpretation of experimental data. It can also
      safeguard against some of the possible misinterpretations that may occur during
      analysis of the small experimental groups that are common in neuroscience and, by
      illuminating analytical error, may aid in design of more efficient experimental
      methods.

PMID- 29380454
TI  - Low levels of hybridization in two species of African driver ants.
AB  - Hybridization in ants can have consequences different from those observed in most
      other species, with many of the potential deleterious effects being mitigated due
      to haplodiploidy and eusociality. In some species where colonies are either
      headed by multiple queens or single queens that mate with many males,
      hybridization is associated with genetic caste determination, where hybrids
      develop into workers and purebred individuals develop into queens. A previous
      study suggested that hybridization occurs between two Dorylus army ant species
      with multiply mated queens. However, the extent and exact pattern of
      hybridization have remained unclear, and its possible effect on caste
      determination has not been investigated. In this study, we aimed to determine the
      extent and direction of hybridization by measuring how frequently hybrids occur
      in colonies of both species, and to investigate the possibility of genetic caste
      determination. We show that hybridization is bidirectional and occurs at equal
      rates in both species. Hybrid workers make up only 1-2% of the population, and
      successful interspecific matings represent approximately 2% of all matings in
      both species. This shows that, although interspecific matings that give rise to
      worker offspring occur regularly, they are much rarer than intraspecific mating.
      Finally, we find no evidence of an association between hybridization and genetic
      caste determination in this population. This means that genetic caste
      determination is not a necessary outcome of hybridization in ants, even in
      species where queens mate with multiple males.

PMID- 29380455
TI  - Fluctuating selection and its (elusive) evolutionary consequences in a wild
      rodent population.
AB  - Temporal fluctuations in the strength and direction of selection are often
      proposed as a mechanism that slows down evolution, both over geological and
      contemporary timescales. Both the prevalence of fluctuating selection and its
      relevance for evolutionary dynamics remain poorly understood however, especially
      on contemporary timescales: unbiased empirical estimates of variation in
      selection are scarce, and the question of how much of the variation in selection
      translates into variation in genetic change has largely been ignored. Using long
      term individual-based data for a wild rodent population, we quantify the
      magnitude of fluctuating selection on body size. Subsequently, we estimate the
      evolutionary dynamics of size and test for a link between fluctuating selection
      and evolution. We show that, over the past 11 years, phenotypic selection on body
      size has fluctuated significantly. However, the strength and direction of genetic
      change have remained largely constant over the study period; that is, the rate of
      genetic change was similar in years where selection favoured heavier vs. lighter
      individuals. This result suggests that over shorter timescales, fluctuating
      selection does not necessarily translate into fluctuating evolution. Importantly
      however, individual-based simulations show that the correlation between
      fluctuating selection and fluctuating evolution can be obscured by the effect of
      drift, and that substantially more data are required for a precise and accurate
      estimate of this correlation. We identify new challenges in measuring the
      coupling between selection and evolution, and provide methods and guidelines to
      overcome them.

PMID- 29380452
TI  - Engineered control of enzyme structural dynamics and function.
AB  - Enzymes undergo a range of internal motions from local, active site fluctuations
      to large-scale, global conformational changes. These motions are often important
      for enzyme function, including in ligand binding and dissociation and even
      preparing the active site for chemical catalysis. Protein engineering efforts
      have been directed towards manipulating enzyme structural dynamics and
      conformational changes, including targeting specific amino acid interactions and
      creation of chimeric enzymes with new regulatory functions. Post-translational
      covalent modification can provide an additional level of enzyme control. These
      studies have not only provided insights into the functional role of protein
      motions, but they offer opportunities to create stimulus-responsive enzymes.
      These enzymes can be engineered to respond to a number of external stimuli,
      including light, pH, and the presence of novel allosteric modulators. Altogether,
      the ability to engineer and control enzyme structural dynamics can provide new
      tools for biotechnology and medicine.

PMID- 29380456
TI  - Uterine natural killer cell progenitor populations predict successful
      implantation in women with endometriosis-associated infertility.
AB  - PROBLEM: Uterine natural killer (uNK) cells play a critical role early in
      gestation. As we previously identified altered uNK cell development in
      endometriosis-associated infertility, we herein sought to characterize natural
      killer (NK) cell profiles in endometriosis that may predict embryo implantation.
      METHOD OF STUDY: Study participants had a surgical diagnosis of endometriosis
      associated infertility. Endometrial tissue and peripheral blood were obtained
      from 58 women. Thirty-three patients underwent artificial reproductive technology
      (IVF, ICSI, or IUI) within a mean of 9.5 months of surgery. NK and hematopoietic
      progenitor cells from endometrium and blood were analyzed by flow cytometry.
      Successful implantation was defined as a positive pregnancy test. RESULTS: In
      successful implantation, populations of endometrial CD34+ hematopoietic stem
      cells were higher (3.97% vs 0.69%; P < .0004), and coexpression of NK cell marker
      CD56 was increased (81.1% vs 60.9%; P < .034) compared with patients who had
      failed implantation. In contrast, levels of blood NK progenitors were similar in
      both groups. CONCLUSION: Our study revealed that uterine NK progenitor cell
      populations are markedly different in patients with endometriosis who proceed to
      successful or failed embryo implantation and may define a novel predictor of
      implantation success. Our findings also highlight the fundamental differences
      inherent in NK cell repertoires between blood and uterine compartments.

PMID- 29380458
TI  - Two paths diverged in the brain, Ray Guillery chose the one less studied.

PMID- 29380459
TI  - Early blindness is associated with increased volume of the uncinate fasciculus.
AB  - Growing evidence demonstrates dramatic structural and functional neuroplastic
      changes in individuals born with early-onset blindness. For example, cross-modal
      sensory processing at the level of the occipital cortex appears to be associated
      with adaptive behaviors in the blind. However, detailed studies examining the
      structural properties of key white matter pathways in other regions of the brain
      remain limited. Given that blind individuals rely heavily on their sense of
      hearing, we examined the structural properties of two important pathways involved
      with auditory processing, namely the uncinate and arcuate fasciculi. High angular
      resolution diffusion imaging (HARDI) tractography was used to examine structural
      parameters (i.e., tract volume and quantitative anisotropy, or QA) of these two
      fasciculi in a sample of 13 early blind individuals and 14 normally sighted
      controls. Compared to controls, early blind individuals showed a significant
      increase in the volume of the left uncinate fasciculus. A small area of increased
      QA was also observed halfway along the right arcuate fasciculus in the blind
      group. These findings contribute to our knowledge regarding the broad
      neuroplastic changes associated with profound early blindness.

PMID- 29380457
TI  - New statin use and left ventricular structure: Estimating long-term associations
      in the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - PURPOSE: Only small and short-term studies have evaluated statins in relation to
      changes in heart structure. We estimated the association between new statin use
      and 10-year remodeling of the left ventricle. METHODS: The Multi-Ethnic Study of
      Atherosclerosis collected data on statin use over approximately 10 years,
      conducting cardiac magnetic resonance (CMR) imaging at baseline and the 10-year
      exam. Participants were free of baseline cardiovascular disease, and we excluded
      users of statins at baseline. Statin initiation was defined as a report of
      current use at any of the 4 subsequent exams. Primary outcomes were the change in
      left ventricular mass index (LVMI; % predicted by height, weight, and sex) and
      mass-to-volume ratio. Associations were estimated in a propensity score-matched
      analysis. RESULTS: A total of 3113 participants (53% female; 40% European
      American, 25% African-American, 22% Hispanic-American, and 13% Chinese-American)
      were eligible; 2431 returned for follow-up CMR imaging after a median of 9.4
      years. Statin therapy (moderate dose, 76%) was started by 36% of participants (N
      = 872). We excluded 42 participants with incident myocardial infarction. Compared
      with nonuse, statin use was associated with less 10-year progression in LVMI (
      2.35 percentage points; 95% CI, -4.24 to -0.47; P = .01) and mass-to-volume ratio
      (-0.03 absolute difference; 95% CI, -0.07 to -0.00; P = .02); effects were small
      in magnitude. A dose response was observed: Higher statin dose was associated
      with less LVMI progression. CONCLUSIONS: In contrast to previous small studies,
      we found very modest associations between statin use and indices of left
      ventricular remodeling over 10 years in this prospective study of a diverse
      cohort.

PMID- 29380460
TI  - Unlicensed medicines use: a UK guideline analysis using AGREE II.
AB  - OBJECTIVES: There is widespread use of unlicensed medicines within primary and
      secondary care but little information is available around how these medicines are
      used. This analysis examines and evaluates the content and quality of relevant
      guidance documentation currently in use within the UK. METHODS: Guidance
      documents were identified through a literature search as well as email requests
      to pharmacy organisations throughout the UK. Unlicensed medicine documentation
      suitable for inclusion in the analysis underwent thematic analysis and quality
      assessment using the AGREE II tool. KEY FINDINGS: Thematic analysis of 52
      guidelines revealed four parent themes: (1) Professional responsibility (2) Usage
      practicalities (3) Risk versus benefit (4) Controlling use. There was variability
      in scores across the AGREE II domains with areas covering Scope and Purpose and
      Clarity of Presentation scoring well. Conversely, an area needing attention was
      Rigour of Development. CONCLUSION: Healthcare organisations would benefit from
      agreeing a 'core content' for the development of unlicensed medicines guidelines
      to ensure consistency and the presence of robust operating systems to deliver
      safe, effective treatment to all NHS patients.

PMID- 29380462
TI  - Cancer prevention-the feasibility and acceptability of promoting breast cancer
      risk reduction in the screening setting through a lifestyle magazine.
AB  - Cancer prevention and early detection strategies are fundamental to reducing
      breast cancer burden. Offering prevention guidance on modifiable risk factors
      within early detection settings is rare. We aimed to evaluate the acceptability
      of a magazine focused on lifestyle and cancer prevention for use in breast
      screening clinics. A lifestyle magazine was developed and distributed within two
      breast screening settings in the West of Scotland over a 2-month period. Women
      were either offered the magazine on arrival or in a self-service format. Uptake
      was recorded by NHS staff. Women's views were sought via an evaluation
      questionnaire. Staff were interviewed on their experiences of intervention
      delivery. Uptake was greatest when offered to attendees (95% vs. 20% self
      service). The evaluation questionnaire response rate was 17.3%. Almost 60% of
      respondents reported an increased knowledge about breast cancer and lifestyle and
      felt motivated to find out more about cancer prevention and 40% expressed
      intentions to make lifestyle changes. Over 90% of respondents thought lifestyle
      factors were important in breast cancer prevention. Staff feedback was positive,
      indicating no detrimental effects on workloads. In conclusion, a cancer
      prevention lifestyle magazine can be successfully delivered in the breast
      screening setting and deserves further exploration for roll out.

PMID- 29380461
TI  - Quantitative susceptibility mapping (QSM) as a means to monitor cerebral hematoma
      treatment.
AB  - BACKGROUND: Quantitative susceptibility mapping (QSM) offers a consistent
      hemorrhage volume measurement independent of imaging parameters. PURPOSE: To
      investigate the magnetic susceptibility of intracerebral hemorrhage (ICH) as a
      quantitative measurement for monitoring treatment in hematoma patients. STUDY
      TYPE: Prospective. POPULATION: Twenty-six patients with acute ICH were recruited
      and enrolled in treatment including surgery or medication (mannitol) for 1 week.
      FIELD STRENGTH/SEQUENCE: A 3D gradient echo sequence at 3.0T. ASSESSMENT: The
      hematoma volumes on computed tomography (CT) and QSM were calculated and used for
      correlation analysis. Magnetic susceptibility changes from pre- to posttreatment
      were calculated and compared to the National Institutes of Health stroke scale
      (NIHSS) measure of neurological deficit for each patient. STATISTICAL TESTS: Mean
      susceptibility values were calculated over each region of interest (ROI). A one
      sample t-test was used to assess the changes of total volumes and mean magnetic
      susceptibility of ICH identified between pre- and posttreatment images (P < 0.05
      was considered significant) and the Bland-Altman analysis with 95% limits of
      agreement (average difference, +/-1.96 SD of the difference). Regression of
      volume measurements on QSM vs. CT and fitted linear regression of mean
      susceptibility vs. CT signal intensity for hematoma regions were conducted in all
      patients. RESULTS: Good correlation was found between hemorrhage volumes
      calculated from CT and QSM (CT volume = 0.94*QSM volume, r = 0.98). Comparison of
      QSM pre- and posttreatment showed that the mean ICH volume was reduced by a
      statistically insignificant amount from 5.74 cm3 to 5.45 cm3 (P = 0.21), while
      mean magnetic susceptibility was reduced significantly from 0.48 ppm to 0.38 ppm
      (P = 0.004). A significant positive association was found between changes in
      magnetic susceptibility values and NIHSS following hematoma treatment (P < 0.01).
      DATA CONCLUSIONS: QSM in hematoma assessment, as compared with CT, offers a
      comparably accurate volume measurement; however, susceptibility measurements may
      enable improved monitoring of ICH treatment compared to volume measurements
      alone. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
      2018;48:907-915.

PMID- 29380463
TI  - Clinicopathologic implications of TNFAIP3/A20 deletions in extranodal NK/T-cell
      lymphoma.
AB  - The A20/Tumor necrosis factor-alpha-induced protein 3 (A20/TNFAIP3) is a negative
      regulator of NF-kappaB signaling. We analyzed the clinicopathologic implications
      of A20 deletions in extranodal NK/T-cell lymphoma (NKTL). Fluorescence in situ
      hybridization analysis of the A20 gene was performed using archived formalin
      fixed tissues in 49 cases of NKTL. Among the 49 NKTL patients (median age, 48 y
      [10-79]), stage I-II (75% [36/48]) and upper aerodigestive tract (UAT)-origin
      (84% [41/49]) were predominant. All A20 deletions were monoallelic and found in
      cases with UAT-origin, accounting for 18% (9/49) of all NKTLs and 22% (9/41) of
      UAT-origin. In univariate analysis, overall survival (OS) and progression-free
      survival (PFS) were associated with stage, international prognostic index (IPI),
      B symptoms and number of extranodal sites, and OS with performance status and non
      UAT-origin, but none with A20 deletion. In multivariate analysis, IPI predicted
      OS (P = .008 [HR = 23.4]) and PFS (P = .005 [HR = 34.0]). Risk was divided by B
      symptoms (P = .001 [OS]; P = .034 [PFS]) in low IPI subset (n = 36), and by A20
      deletion (P = .029 [PFS]) in high IPI subset (n = 13). These results suggest a
      clinicopathologic implication of A20 in progression of NKTL.

PMID- 29380464
TI  - Hypothalamic and liver transcriptome from two crucial life-history stages in a
      migratory songbird.
AB  - NEW FINDINGS: What is the central question of this study? What are the molecular
      underpinnings of the seasonal adaptation in a latitudinal migratory songbird?
      What is the main finding and its importance? We found changes in mRNA levels
      after a photoperiod-induced alteration of seasonal state in a captive long
      distance latitudinal avian migrant. The hypothalamus and liver transcriptomes
      revealed genes involved in the regulatory and functional pathways between non
      migratory and migratory states. Our results provide insights into mechanisms
      underlying homeostasis during seasonal changes that are conserved across most
      species, including humans. ABSTRACT: Very little is understood about genetic
      mechanisms underlying the onset of spring migration in latitudinal avian
      migrants. To gain insight into the genetic architecture of the hypothalamus and
      liver tissues of a long-distance migrant, we examined and compared the
      transcriptome profile of captive night-migratory black-headed buntings (Emberiza
      melanocephala) between photoperiod-induced winter non-migratory (WnM) and spring
      migratory (SM) life-history states under short and long days, respectively. High
      throughput 454 pyrosequenced transcripts were mapped initially with reference to
      the genome of two phylogenetically close species, Taeniopygia guttata and
      Ficedula albicollis. The F. albicollis genome gave higher annotation results and
      was used for further analysis. A total of 216 (78 in hypothalamus; 138 in liver)
      genes were found to be expressed differentially between the WnM and SM life
      history states. These genes were enriched for physiological pathways that might
      be involved in the regulation of seasonal migrations in birds. For example, genes
      for the ATP binding pathway in the hypothalamus were expressed at a significantly
      higher level in SM than in the WnM life-history state. Likewise, upregulated
      genes associated with the myelin sheath and focal adhesion were enriched in the
      hypothalamus, and those with cell-to-cell junction, intracellular protein
      transport, calcium ion transport and small GTPase-mediated signal transduction
      were enriched in the liver. Many of these genes are a part of physiological
      pathways potentially involved in the regulation of seasonal migration in birds.
      These results show molecular changes at the regulatory and metabolic levels
      associated with seasonal transitions in a long-distance migrant and provide the
      basis for future studies aimed at unravelling the genetic control of migration in
      birds.

PMID- 29380465
TI  - Simultaneous Binding of Hybrid Molecules Constructed with Dual DNA-Binding
      Components to a G-Quadruplex and Its Proximal Duplex.
AB  - A G-quadruplex (quadruplex) is a nucleic acid secondary structure adopted by
      guanine-rich sequences and is considered to be relevant to various
      pharmacological and biological contexts. Although a number of researchers have
      endeavored to discover and develop quadruplex-interactive molecules, poor ligand
      designability originating from topological similarity of the skeleton of diverse
      quadruplexes has remained a bottleneck for gaining specificity for individual
      quadruplexes. This work reports on hybrid molecules that were constructed with
      dual DNA-binding components, a cyclic imidazole/lysine polyamide (cIKP), and a
      hairpin pyrrole/imidazole polyamide (hPIP), with the aim toward specific
      quadruplex targeting by reading out the local duplex DNA sequence adjacent to
      designated quadruplexes in the genome. By means of circular dichroism (CD),
      fluorescence resonance energy transfer (FRET), surface plasmon resonance (SPR),
      and NMR techniques, we showed the dual and simultaneous recognition of the
      respective segment via hybrid molecules, and the synergistic and mutual effect of
      each binding component that was appropriately linked on higher binding affinity
      and modest sequence specificity. Monitoring quadruplex and duplex imino protons
      of the quadruplex/duplex motif titrated with hybrid molecules clearly revealed
      distinct features of the binding of hybrid molecules to the respective segments
      upon their simultaneous recognition. A series of the systematic and detailed
      binding assays described here showed that the concept of simultaneous recognition
      of quadruplex and its proximal duplex by hybrid molecules constructed with the
      dual DNA-binding components may provide a new strategy for ligand design,
      enabling targeting of a large variety of designated quadruplexes at specific
      genome locations.

PMID- 29380466
TI  - Polyvalent Display of Biomolecules on Live Cells.
AB  - Surface display of biomolecules on live cells offers new opportunities to treat
      human diseases and perform basic studies. Existing methods are primarily focused
      on monovalent functionalization, that is, the display of single biomolecules
      across the cell surface. Here we show that the surface of live cells can be
      functionalized to display polyvalent biomolecular structures through two-step
      reactions under physiological conditions. This polyvalent functionalization
      enables the cell surface to recognize the microenvironment one order of magnitude
      more effectively than with monovalent functionalization. Thus, polyvalent display
      of biomolecules on live cells holds great potential for various biological and
      biomedical applications.

PMID- 29380467
TI  - Concentration-Gradient-Method for sulphur and strontium isotope ratio
      determination by quadrupole-based inductively coupled plasma mass spectrometry in
      gypsum.
AB  - RATIONALE: The concentration-gradient-method (CGM) was previously introduced as a
      precise and accurate method for isotope ratio determination by quadrupole-based
      inductively coupled plasma mass spectrometry (ICP-QMS). The investigation of its
      potential and advantages in the analysis of analytes with a poor signal-noise
      ratio (S/N) is important to establish routine isotope ratio analysis industrial
      applications on these widely used instruments. METHODS: The CGM was applied on
      isotope measurements of Sr near its limit of quantification (LOQ) and of sulphur
      where there was a massively interfered 32 S isotope signal in gypsum samples of
      different origin, in order to demonstrate the advantages of the CGM over the
      commonly used measurement and evaluation approach. The comparison between the CGM
      and the classical measurement and evaluation approach was performed with high and
      low concentration Sr standard solutions, to prove the robustness of the isotope
      ratio determination. RESULTS: In both cases the CGM reached a recovery rate of
      approximately 103 %, whereas the classical approach became increasingly
      inaccurate at lower S/N (recovery of 123 %). In the case of sulphur isotope ratio
      determination only the CGM enabled a differentiation between geogenic and flue
      gas desulphurisation plant-originated gypsum samples. CONCLUSIONS: The robustness
      of the CGM approach was illustrated for gypsum samples with trace strontium
      concentration and its general applicability to the determination of sulphur
      isotope ratios by means of quadrupole-based ICP-MS was demonstrated using the
      example of sulphur in gypsum.

PMID- 29380468
TI  - Trends in pediatric liver transplant donors and deceased donor circumstance of
      death in the United States, 2002-2015.
AB  - While much of the discussion regarding expanding the donor pool for pediatric
      liver transplantation has surrounded the use of technical variant grafts, little
      attention has been directed toward changes in the deceased donor population. The
      aim of this study was to investigate trends in the circumstance of the death of
      deceased donors used for pediatric liver transplantation. All pediatric liver
      transplant recipients transplanted between 2002 and 2015 were identified in the
      UNOS database and were categorized based on the donor circumstance of death.
      There was no significant correlation between year of transplantation and number
      of pediatric liver transplants performed, pediatric donors, split livers, or
      living donors. There was a significant downward trend in donors from motor
      vehicle fatalities and an upward trend in suicide, non-MVA, and death due to
      natural causes. There was also an upward trend in drowning, one of the most
      common mechanisms of death among non-MVA in 2015. While the number of donors who
      died in MVA has fallen, the number of deceased donors who died from suicide,
      natural causes, and non-MVA, especially drowning, has increased, maintaining the
      overall number of pediatric deceased donor livers transplanted.

PMID- 29380470
TI  - Hemispheric asymmetries in the orientation and location of the lateral geniculate
      nucleus in dyslexia.
AB  - Human brain asymmetry reflects normal specialization of functional roles and may
      derive from evolutionary, hereditary, developmental, experiential, and
      pathological factors (Toga & Thompson, 2003). Geschwind and Galaburda (1985)
      suggested that processing difficulties in dyslexia are due to structural
      differences between hemispheres. Because of its potential significance to the
      controversial magnocellular theory of dyslexia, we investigated hemispheric
      differences in the human lateral geniculate nucleus (LGN), the primary visual
      relay and control nucleus in the thalamus, in subjects with dyslexia compared to
      normal readers. We acquired and averaged multiple high-resolution proton density
      (PD) weighted structural magnetic resonance imaging (MRI) volumes to measure in
      detail the anatomical boundaries of the LGN in each hemisphere. We observed
      hemispheric asymmetries in the orientation of the nucleus in subjects with
      dyslexia that were absent in controls. We also found differences in the location
      of the LGN between hemispheres in controls but not in subjects with dyslexia.
      Neither the precise anatomical differences in the LGN nor their functional
      consequences are known, nor is it clear whether the differences might be causes
      or effects of dyslexia.

PMID- 29380471
TI  - Management of Challenging Esthetic Anterior Cases with Limited Restorative Space:
      A Clinical Report.
AB  - With careful restorative planning and surgical placement, dental implants can be
      used to support and retain a wide range of esthetic prostheses. When implant
      planning or surgical executions are less than ideal, however, the resulting
      restorative space can be a significant obstacle to successful treatment. The aim
      of this article is to describe the use of a customized anterior bar to support a
      partial overdenture prosthesis for a youthful patient with a high smile line and
      a limited restorative space of 6 mm. Details of the treatment and an illustration
      of the customized design are also presented.

PMID- 29380469
TI  - Emergence of the neural network underlying phonological processing from the
      prereading to the emergent reading stage: A longitudinal study.
AB  - Numerous studies have shown that phonological skills are critical for successful
      reading acquisition. However, how the brain network supporting phonological
      processing evolves and how it supports the initial course of learning to read is
      largely unknown. Here, for the first time, we characterized the emergence of the
      phonological network in 28 children over three stages (prereading, beginning
      reading, and emergent reading) longitudinally. Across these three time points,
      decreases in neural activation in the left inferior parietal cortex (LIPC) were
      observed during an audiovisual phonological processing task, suggesting a
      specialization process in response to reading instruction/experience.
      Furthermore, using the LIPC as the seed, a functional network consisting of the
      left inferior frontal, left posterior occipitotemporal, and right angular gyri
      was identified. The connection strength in this network co-developed with the
      growth of phonological skills. Moreover, children with above-average gains in
      phonological processing showed a significant developmental increase in connection
      strength in this network longitudinally, while children with below-average gains
      in phonological processing exhibited the opposite trajectory. Finally, the
      connection strength between the LIPC and the left posterior occipitotemporal
      cortex at the prereading level significantly predicted reading performance at the
      emergent reading stage. Our findings highlight the importance of the early
      emerging phonological network for reading development, providing direct evidence
      for the Interactive Specialization Theory and neurodevelopmental models of
      reading.

PMID- 29380472
TI  - Conformation-Enabled Total Syntheses of Ohmyungsamycins A and B and Structural
      Revision of Ohmyungsamycin B.
AB  - The first total syntheses of the bioactive cyclodepsipeptides ohmyungsamycin A
      and B are described. Key features of our synthesis include the concise
      preparation of a linear cyclization precursor that consists of N-methyl amides
      and non-proteinogenic amino acids, and its macrolactamization from a bent
      conformation. The proposed structure of ohmyungsamycin B was revised based on its
      synthesis. The cyclic core of the ohmyungsamycins was shown to be responsible for
      the excellent antituberculosis activity, and ohmyungsamycin variants with
      truncated chains were evaluated for their biological activity.

PMID- 29380473
TI  - Size-Selective Exclusion Effects of Liquid Crystalline Tactoids on Nanoparticles:
      A Separation Method.
AB  - Liquid crystalline tactoids are anisotropic microdroplets existing in isotropic
      phases. We studied the structure and evolution of tactoids in the presence of
      doping nanoparticles by electron microscopy at the resolution of individual
      mesogens and observed size-selective exclusion effects of liquid crystalline
      tactoids on foreign nanoparticles. We applied this principle to the separation of
      polymer nanospheres, gold nanoparticles, and magnetic nanoparticles by size.
      These results indicate a new way to size-selectively separate nanoparticles using
      lyotropic liquid crystals, in which nanoparticles smaller than a threshold size
      will be selectively transferred from the disordered phase into the ordered phase
      by tactoids during the phase separation process.

PMID- 29380474
TI  - Mental health assessment: Inference, explanation, and coherence.
AB  - Mental health professionals such as psychiatrists and psychotherapists assess
      their patients by identifying disorders that explain their symptoms. This
      assessment requires an inference to the best explanation that compares different
      disorders with respect to how well they explain the available evidence. Such
      comparisons are captured by the theory of explanatory coherence that states 7
      principles for evaluating competing hypotheses in the light of evidence. The
      computational model ECHO shows how explanatory coherence can be efficiently
      computed. We show the applicability of explanatory coherence to mental health
      assessment by modelling a case of psychiatric interviewing and a case of
      psychotherapeutic evaluation. We argue that this approach is more plausible than
      Bayesian inference and hermeneutic interpretation.

PMID- 29380475
TI  - Is there an optimal organ acceptance rate for pediatric heart transplantation: "A
      sweet spot"?
AB  - Despite a limited supply of donors, potential donor hearts are often declined for
      subjective concerns regarding organ quality. This analysis will investigate the
      relationship between donor heart AR and patient outcome at pediatric transplant
      centers. The UNOS database was used to identify all match runs for pediatric
      candidates (age < 18 years) from 2008 through March 2015 in which a heart offer
      was ultimately placed. Centers which received >=10 offers/y were included (10 634
      offers, 38 centers). Transplant centers were stratified based on their AR: low
      (<20%, n = 13), medium (20%-40%, n = 16), or high (>40%, n = 9). Low AR centers
      experienced worse negative WL outcome compared with medium (P = .022) and high (P
      = .004) AR centers. Low AR centers had similar post-transplant graft survival to
      medium (P = .311) or high (P = .393) AR centers; however, medium AR centers had
      better post-transplant graft survival than high AR centers (P = .037). E-F
      survival from listing regardless of transplant was worse for low AR centers
      compared with medium (P < .001) or high (P = .001) AR centers. Low AR centers
      experience worse WL outcomes without improvement in post-transplant outcomes.
      High AR centers experience higher post-transplant graft failure than medium AR
      centers. AR of 20%-40% appears to have optimal WL and post-transplant outcomes.

PMID- 29380476
TI  - Light-Activated Control of Translation by Enzymatic Covalent mRNA Labeling.
AB  - Activation of cellular protein expression upon visible-light photocleavage of
      small-molecule caging groups covalently attached to the 5' untranslated region
      (5' UTR) of an mRNA was achieved. These photocleavable caging groups are
      conjugated to in vitro transcribed mRNA (IVT-mRNA) through RNA
      transglycosylation, an enzymatic process in which a bacterial tRNA guanine
      transglycosylase (TGT) exchanges a guanine nucleobase in a specific 17-nucleotide
      motif (Tag) for synthetic pre-queuosine1 (preQ1 ) derivatives. The caging groups
      severely reduce mRNA translation efficiency when strategically placed in the 5'
      UTR. Using this method, we demonstrate the successful spatiotemporal
      photoregulation of gene expression with single-cell precision. Our method can be
      applied to therapeutically relevant chemically modified mRNA (mod-mRNA)
      transcripts. This strategy provides a modular and efficient approach for
      developing synthetic gene regulatory circuits, biotechnological applications, and
      therapeutic discovery.

PMID- 29380477
TI  - Thinking about complexity in health: A systematic review of the key systems
      thinking and complexity ideas in health.
AB  - RATIONALE, AIMS, AND OBJECTIVES: As the Sustainable Development Goals are rolled
      out worldwide, development leaders will be looking to the experiences of the past
      to improve implementation in the future. Systems thinking and complexity science
      (ST/CS) propose that health and the health system are composed of dynamic actors
      constantly evolving in response to each other and their context. While offering
      practical guidance for steering the next development agenda, there is no
      consensus as to how these important ideas are discussed in relation to health.
      This systematic review sought to identify and describe some of the key terms,
      concepts, and methods in recent ST/CS literature. METHOD: Using the search terms
      "systems thinkin * AND health OR complexity theor* AND health OR complex adaptive
      system* AND health," we identified 516 relevant full texts out of 3982 titles
      across the search period (2002-2015). RESULTS: The peak number of articles were
      published in 2014 (83) with journals specifically focused on medicine/healthcare
      (265) and particularly the Journal of Evaluation in Clinical Practice (37)
      representing the largest number by volume. Dynamic/dynamical systems (n = 332),
      emergence (n = 294), complex adaptive system(s) (n = 270), and
      interdependent/interconnected (n = 263) were the most common terms with systems
      dynamic modelling (58) and agent-based modelling (43) as the most common methods.
      CONCLUSIONS: The review offered several important conclusions. First, while there
      was no core ST/CS "canon," certain terms appeared frequently across the reviewed
      texts. Second, even as these ideas are gaining traction in academic and
      practitioner communities, most are concentrated in a few journals. Finally,
      articles on ST/CS remain largely theoretical illustrating the need for further
      study and practical application. Given the challenge posed by the next phase of
      development, gaining a better understanding of ST/CS ideas and their use may lead
      to improvements in the implementation and practice of the Sustainable Development
      Goals.

PMID- 29380478
TI  - A Comparison of Care Delivered in Hospital-based and Freestanding Emergency
      Departments.
AB  - OBJECTIVE: We compare case mix, hospitalization rates, length of stay (LOS), and
      resource use in independent freestanding emergency departments (FSEDs) and
      hospital-based emergency departments (H-EDs). METHODS: Data from 74 FSEDs (2013
      2015) in Texas and Colorado were compared to H-ED data from the 2013-2014
      National Hospital Ambulatory Medical Care Survey. In the unrestricted sample,
      large differences in visit characteristics (e.g., payer and case mix) were found
      between patients that use FSEDs compared to H-EDs. Therefore, we restricted our
      analysis to patients commonly treated in both settings (<65 years, privately
      insured, nonambulance) and used inverse propensity score weighting (IPW) to
      balance the two settings on observable patient characteristics. We then compared
      ED LOS and as well as hospital admission rates and resource utilization rates in
      the IPW-weighted samples. RESULTS: Before balancing, FSEDs saw more young adults
      (age 25-44) and fewer older adults (age 45-64) than H-EDs. FSED patients had
      fewer comorbidities, more injuries and respiratory infections, and fewer
      diagnoses of chest or abdominal pain. In balanced samples, LOS for FSED visits
      was 46% shorter (60 minutes) than H-ED patients. Hospital admission rates were
      37% lower overall (95% confidence interval = -51% to -23%) in FSEDs and varied
      considerably by primary discharge diagnosis. X-ray and electrocardiogram use was
      significantly lower at FSEDs while others measures of resource utilization were
      similar (ultrasound, computed tomography scans, and laboratory tests).
      CONCLUSION: In this sample of FSEDs, a greater proportion of younger patients
      with fewer comorbidities and more injuries and respiratory system diseases were
      evaluated, and almost all patients had private health insurance. When restricted
      to < 65 years, privately insured, and nonambulance patients in both samples, LOS
      was considerably shorter and hospital admission rates lower at FSEDs, as well as
      the use of some diagnostic testing. This study is limited as diagnoses codes may
      not fully capture severity and patients who perceived greater need of hospital
      admission may have chosen a H-ED over FSEDs.

PMID- 29380479
TI  - Safety and efficacy of foscarnet for the management of ganciclovir-resistant or
      refractory cytomegalovirus infections: A single-center study.
AB  - BACKGROUND: Infection with cytomegalovirus (CMV) is an important cause of
      morbidity and mortality following solid organ transplantation. Resistance to
      ganciclovir can rarely develop via mutations in UL97 or UL54. There are limited
      published studies assessing the safety and efficacy of foscarnet for the
      management of ganciclovir-resistant or refractory cytomegalovirus infection and
      many centers are reluctant to utilize this important therapy because of concerns
      about toxicity. METHODS: Solid organ recipients transplanted between January 1,
      2006 and December 31, 2014 who received at least 1 dose of foscarnet were
      retrospectively reviewed to assess treatment outcomes, tolerability, and safety
      of foscarnet. RESULTS: Ten of 31 (32.3%) patients who received foscarnet during
      the study period died during treatment with foscarnet, whereas all 21 surviving
      recipients successfully cleared infection. Of these surviving patients, 3 (14.3%)
      developed significant renal dysfunction, defined as >25% decline in estimated
      glomerular filtration rate during treatment; one-third had definitive renal
      biopsy results consistent with foscarnet-induced toxicity. CONCLUSION: Although
      mortality was high in this population, foscarnet use, with proper precautions,
      was generally safe and significant renal dysfunction was lower than previously
      reported in other sources, even with extended use.

PMID- 29380480
TI  - Recommendations for pharmacological clinical trials in children with functional
      constipation: The Rome foundation pediatric subcommittee on clinical trials.
AB  - BACKGROUND: Evidence for the efficacy of commonly used drugs in the treatment of
      childhood functional constipation (FC) is scarce, studies are often of low
      quality and study designs are heterogeneous. Thus, recommendations for the design
      of clinical trials in childhood FC are needed. PURPOSE: Members of the Rome
      Foundation and a member of the Pediatric Committee of the European Medicines
      Agency formed a committee to create recommendations for the design of clinical
      trials in children with FC. KEY RECOMMENDATIONS: This committee recommends
      conducting randomized, double-blind, placebo-controlled, parallel-group clinical
      trials to assess the efficacy of new drugs for the treatment of childhood FC.
      Pediatric study participants should be included based on fulfilling the Rome IV
      criteria for FC. A treatment free run-in period for baseline assessment is
      recommended. The trial duration should be at least 8 weeks. Treatment success is
      defined as no longer meeting the Rome IV criteria for FC. Stool consistency
      should be reported based on the Bristol Stool Scale. Endpoints of drug efficacy
      need to be tailored to the developmental age of the patient population.

PMID- 29380482
TI  - In Reply to the Letter to the Editor from Anderson et al.: An Induced Pluripotent
      Stem Cell Patient Specific Model of Complement Factor H (Y402H) Polymorphism
      Displays Characteristic Features of Age-Related Macular Degeneration and
      Indicates a Beneficial Role for UV Light Exposure.

PMID- 29380483
TI  - Effect of Different Laser Treatments on the Bond Strength of Intracanal Fiber
      Posts Cemented with a Self-Adhesive Resin Cement.
AB  - PURPOSE: To evaluate the influence of laser-activated irrigation by Er:YAG and
      Er:YSGG (LAI) protocols and Nd:YAG laser irradiation on the bond strength of self
      adhesively cemented fiber posts to root canal dentine. MATERIALS AND METHODS: The
      study sample consisted of 84 human single-rooted permanent teeth instrumented
      with ProTaper Next technique. After obturation, post space preparations were
      created for fiber-reinforced composite posts. The prepared specimens were divided
      according to the laser treatment of the post space preparations: group 1: LAI
      (Er:YAG) + saline solution (pulse energy: 20 mJ, repetition rate: 15 Hz); group
      2: LAI (Er:YAG) + QMiX solution (pulse energy: 20 mJ, repetition rate: 15 Hz);
      group 3: LAI (Er,Cr:YSGG) + saline solution (pulse energy: 62.5 mJ, 20 Hz); group
      4: LAI (Er,Cr:YSGG) + QMiX (pulse energy: 62.5 mJ, 20 Hz); Nd:YAG laser (pulse
      energy: 100 mJ, 10 Hz). Fiber-reinforced posts were cemented with a self-adhesive
      cement. The bond strength was evaluated by the push-out bond strength test, and
      the mode of failure was determined under a stereomicroscope. Kruskal-Wallis test
      was used for the intergroup comparative analysis with 5% level of significance.
      RESULTS: The highest bond strength was recorded in the Er:YAG + QMiX group (mean
      3.401 MPa) (p < 0.05), followed by the Er,Cr:YSGG and the Er:YAG + saline
      solution (mean 1.111 MPa and 1.094 MPa, respectively), which did not differ
      significantly (p = 0.232). The irradiation with the Nd:YAG laser caused similar
      bond strength as the Er,Cr:YSGG + QMiX (p = 0.942). CONCLUSION: All laser
      protocols enhanced the bond strength of the self-adhesive cement in root canals
      compared to only saline irrigation. The bond strength of the self-adhesive cement
      depended on the laser parameters and irrigant used for the LAI.

PMID- 29380484
TI  - Deja Vu.

PMID- 29380485
TI  - Neuromodulation with single-element transcranial focused ultrasound in human
      thalamus.
AB  - Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical
      tissue in humans. tFUS confers high spatial resolutions with deep focal lengths
      and as such, has the potential to noninvasively modulate neural targets deep to
      the cortex in humans. We test the ability of single-element tFUS to noninvasively
      modulate unilateral thalamus in humans. Participants (N = 40) underwent either
      tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that
      contains the ventro-posterior lateral (VPL) nucleus of thalamus. Somatosensory
      evoked potentials (SEPs) were recorded from scalp electrodes contralateral to
      median nerve stimulation. Activity of the unilateral sensory thalamus was indexed
      by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity
      by subsequent inflexions of the SEP and through time/frequency analysis.
      Participants also under went tactile behavioral assessment during either the tFUS
      or sham condition in a separate experiment. A detailed acoustic model using
      computed tomography (CT) and magnetic resonance imaging (MRI) is also presented
      to assess the effect of individual skull morphology for single-element deep brain
      neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited
      the amplitude of the P14 SEP as compared to sham. There is evidence of
      translation of this effect to time windows of the EEG commensurate with SI and
      SII activities. These results were accompanied by alpha and beta power
      attenuation as well as time-locked gamma power inhibition. Furthermore,
      participants performed significantly worse than chance on a discrimination task
      during tFUS stimulation.

PMID- 29380486
TI  - Brief report: Exploring the benefits of a peer-tutored physical education
      programme among high school students with intellectual disability.
AB  - BACKGROUND: The purpose of this study was to explore possible benefits of a peer
      tutored physical education programme (PTPE) in comparison with school physical
      education (SPE) in high school students with intellectual disability. METHOD:
      Nineteen students with intellectual disabilities (15 boys, mean age 17.4 +/- 1.7
      years) were monitored during three PTPE and three SPE classes. A factorial RM
      ANOVA was used to test differences on objective measured physical activity (PA),
      enjoyment and exertion during the two conditions, considering participants'
      weight condition as independent factor. RESULTS: During PTPE, participants
      reported higher light intensity PA, enjoyment and exertion than during SPE.
      Participants with overweight showed less inactive time and higher light intensity
      PA during PTPE than during SPE. CONCLUSIONS: The peer-tutored programme was
      beneficial for adolescents with intellectual disability, particularly for those
      in overweight condition. The higher enjoyment found during PTPE may encourage
      exercise participation of students with intellectual disability.

PMID- 29380487
TI  - Effect of Silane Heat Treatment by Laser on the Bond Strength of a Repair
      Composite to Feldspathic Porcelain.
AB  - PURPOSE: Ceramic restoration fracture may occur in the oral cavity. Intraoral
      repair of fractured porcelain could be advantageous to both patient and dentist.
      The aim of this study was to evaluate the effect of heat treatment of the silane
      coupling agent by Er:YAG and CO2 lasers on the microshear bond strength of a
      repair composite to feldspathic porcelain. MATERIALS AND METHODS: Sixty ceramic
      blocks were prepared and randomly divided into six groups (n = 10): (i) HF +
      silane (HS); (ii) silane + CO2 laser (SC); (iii) CO2 laser + silane (CS); (iv)
      silane + Er:YAG laser (SE); (v) Er:YAG laser + silane (ES); (vi) bur + HF +
      silane (BuHS). An adhesive resin was applied to the prepared ceramic surfaces and
      light-cured. Two transparent plastic tubes were placed perpendicularly to each
      ceramic block. The composite resin was then placed on the treated ceramic surface
      and light-cured for 40 seconds. The bonded blocks were stored in distilled water
      at 37 degrees C for 24 hours and subjected to 3000 thermocycles. Microshear bond
      strength (MUSBS) tests were performed using a wire and loop method. Data were
      analyzed using one-way ANOVA and Duncan's multiple range tests (p <= 0.05).
      RESULTS: The comparison of the mean MUSBS values showed no significant
      differences between the ES and HS groups (p = 0.914). On the other hand, the
      specimens in these groups exhibited significantly higher bond strengths than
      those in the other groups (p < 0.01). The mean MUSBS of the BuHS group was
      statistically similar to that of CS and SE groups (p > 0.05). The MUSBS for the
      SC group was significantly lower than that of the other groups (p < 0.01), with
      the exception of the CS group (p = 0.674). CONCLUSIONS: Treatment with Er:YAG
      laser prior to silane application can be as effective as HF etching. Heat
      treatment of silane by CO2 or Er:YAG lasers does not improve the bond strength
      between feldspathic porcelain and composite resin.

PMID- 29380488
TI  - Validation and Clinical Utility of the hERG IC50:Cmax Ratio to Determine the Risk
      of Drug-Induced Torsades de Pointes: A Meta-Analysis.
AB  - BACKGROUND: Use of the QT interval corrected for heart rate (QTc) on the
      electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit
      drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory
      concentration of the hERG channel (hERG IC50) to the peak serum concentration of
      unbound drug (Cmax ) is used during drug development to screen out chemical
      entities likely to cause TdP. PURPOSE: To validate the use of the hERG IC50:Cmax
      ratio to predict TdP risk from a culprit drug by its correlation with TdP
      incidence. DATA SOURCES: Medline (between 1966 and March 2017) was accessed for
      hERG IC50 and Cmax values from the antihistamine, fluoroquinolone, and
      antipsychotic classes to identify cases of drug-induced TdP. Exposure to a
      culprit drug was estimated from annual revenues reported by the manufacturer.
      STUDY SELECTION: Inclusion criteria for TdP cases were provision of an ECG
      tracing that demonstrated QTc prolongation with TdP and normal serum values of
      potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm
      disturbance and those involving a drug interaction were excluded. DATA EXTRACTION
      AND SYNTHESIS: The Meta-Analysis of Observational Studies in Epidemiology
      checklist was used for epidemiological data extraction by two authors. MAIN
      OUTCOME AND MEASURE: Negligible risk drugs were defined by an hERG IC50:Cmax
      ratio that correlated with less than a 5% chance of one TdP event for every 100
      million exposures (relative risk [RR] 1.0). RESULTS: The hERG IC50:Cmax ratio
      correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, p<0.0001),
      a ratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine;
      ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50
      include astemizole, risperidone, haloperidol, and thioridazine. CONCLUSIONS: The
      hERG IC50:Cmax ratio was correlated with TdP incidence for culprit drugs. This
      validation provides support for the potential use of the hERG IC50:Cmax ratio for
      clinical decision making in instances of drug selection where TdP risk is a
      concern.

PMID- 29380490
TI  - Evaluation of primary stability in modified implants: Analysis by resonance
      frequency and insertion torque.
AB  - BACKGROUND: Changes in the macrogeometry of dental implants are known to
      influence primary stability and the osseointegration process. PURPOSE: The
      purpose of the present in vitro study was to evaluate the mechanical behavior of
      geometric changes in the apex region of dental implants. METHODS: Thirty-five
      cylindrical dental implants (Titamax Ti; Neodent) were machined at the apical
      third to reproduce the experimental groups: without apical cut (Wc), apical bi
      split cut, apical tri-split cut, apical quadri-split cut (Qs). One (control
      group) (Titamax Ti Ex) (n = 7) without any modifications was added. The implants
      had the same final dimensions (4.1 x 11 mm2 ). All implants were inserted into
      artificial bone blocks and were evaluated by insertion torque and resonance
      frequency by ISQ values (Osstell). Two-tailed analysis of variance (One-way
      ANOVA) and Tukey's post-test (P < .05). RESULTS: Control and Qs implants showed a
      significant increase of the insertion torque (P < .001). For the resonance
      frequency, Wc and (control) implants had the greatest ISQ values. However,
      there's no significant difference between (control) and Qs for the ISQ values (P
      < .001). CONCLUSION: Within the limitations of the present study, the proposed
      geometries at the apical third of dental implants greatly influenced its
      insertion torque and primary stability in vitro.

PMID- 29380491
TI  - Extracorporeal photopheresis as second-line treatment therapy in life-threatening
      primary graft dysfunction following lung transplantation.
AB  - ECP is an established "second-line" treatment for CLAD/BOS. Recently, ECP was
      used for the first time in an adolescent CF patient as a "second-line" treatment
      therapy in life-threatening primary graft dysfunction following lung
      transplantation who deteriorated despite extensive treatment including ECMO and
      ATG. Within 10 days after initiation of ECP twice weekly, allograft function and
      clinical status improved significantly and the patient was weaned from mechanical
      ventilation support. ECP has been continued every 2 weeks since. Two hundred days
      after lung transplantation, the patient has an acceptable allograft function
      (FEV1 67%) and no signs of allograft rejection. We advocate that use of ECP and
      its immunomodulatory effects should be evaluated in the early period following
      lung transplantation.

PMID- 29380489
TI  - Linking late cognitive outcome with glioma surgery location using resection
      cavity maps.
AB  - Patients with a diffuse glioma may experience cognitive decline or improvement
      upon resective surgery. To examine the impact of glioma location, cognitive
      alteration after glioma surgery was quantified and related to voxel-based
      resection probability maps. A total of 59 consecutive patients (range 18-67 years
      of age) who had resective surgery between 2006 and 2011 for a supratentorial
      nonenhancing diffuse glioma (grade I-III, WHO 2007) were included in this
      observational cohort study. Standardized neuropsychological examination and MRI
      were obtained before and after surgery. Intraoperative stimulation mapping guided
      resections towards neurological functions (language, sensorimotor function, and
      visual fields). Maps of resected regions were constructed in standard space.
      These resection cavity maps were compared between patients with and without new
      cognitive deficits (z-score difference >1.5 SD between baseline and one year
      after resection), using a voxel-wise randomization test and calculation of false
      discovery rates. Brain regions significantly associated with cognitive decline
      were classified in standard cortical and subcortical anatomy. Cognitive
      improvement in any domain occurred in 10 (17%) patients, cognitive decline in any
      domain in 25 (42%), and decline in more than one domain in 10 (17%). The most
      frequently affected subdomains were attention in 10 (17%) patients and
      information processing speed in 9 (15%). Resection regions associated with
      decline in more than one domain were predominantly located in the right
      hemisphere. For attention decline, no specific region could be identified. For
      decline in information speed, several regions were found, including the frontal
      pole and the corpus callosum. Cognitive decline after resective surgery of
      diffuse glioma is prevalent, in particular, in patients with a tumor located in
      the right hemisphere without cognitive function mapping.

PMID- 29380492
TI  - A genome-wide association study for fat-related traits computed by image analysis
      in Japanese Black cattle.
AB  - The objective of this study was to identify genomic regions associated with fat
      related traits using a Japanese Black cattle population in Hyogo. From 1836
      animals, those with high or low values were selected on the basis of corrected
      phenotype and then pooled into high and low groups (n = 100 each), respectively.
      DNA pool-based genome-wide association study (GWAS) was performed using Illumina
      BovineSNP50 BeadChip v2 with three replicate assays for each pooled sample. GWAS
      detected that two single nucleotide polymorphisms (SNPs) on BTA7 (ARS-BFGL-NGS
      35463 and Hapmap23838-BTA-163815) and one SNP on BTA12 (ARS-BFGL-NGS-2915)
      significantly affected fat percentage (FAR). The significance of ARS-BFGL-NGS
      35463 on BTA7 was confirmed by individual genotyping in all pooled samples.
      Moreover, association analysis between SNP and FAR in 803 Japanese Black cattle
      revealed a significant effect of SNP on FAR. Thus, further investigation of these
      regions is required to identify FAR-associated genes and mutations, which can
      lead to the development of DNA markers for marker-assisted selection for the
      genetic improvement of beef quality.

PMID- 29380493
TI  - A Water-Soluble Warped Nanographene: Synthesis and Applications for Photoinduced
      Cell Death.
AB  - Nanographene, a small piece of graphene, has attracted unprecedented interest
      across diverse scientific disciplines particularly in organic electronics. The
      biological applications of nanographenes, such as bioimaging, cancer therapies
      and drug delivery, provide significant opportunities for breakthroughs in the
      field. However, the intrinsic aggregation behavior and low solubility of
      nanographenes, which stem from their flat structures, hamper their development
      for bioapplications. Herein, we report a water-soluble warped nanographene (WNG)
      that can be easily synthesized by sequential regioselective C-H borylation and
      cross-coupling reactions of the saddle-shaped WNG core structure. The saddle
      shaped structure and hydrophilic tetraethylene glycol chains impart high water
      solubility to the WNG. The water-soluble WNG possesses a range of promising
      properties including good photostability and low cytotoxicity. Moreover, the
      water-soluble WNG was successfully internalized into HeLa cells and promoted
      photoinduced cell death.

PMID- 29380494
TI  - Effect of pH on Abeta42 Monomer and Fibril-like Oligomers-Decoding in Silico of
      the Roles of pK Values of Charged Residues.
AB  - Amyloid beta-peptide (Abeta) is the key to developing Alzheimer's disease.
      Experiments have confirmed that different acidity influences directly not only
      the structural morphology and population of Abeta oligomers, but also the
      toxicity. The atomic-level association between the pH, charged residues, and
      Abeta properties remains obscure. Herein, conformational changes of Abeta42
      monomer, fibril-like trimer, and pentamer in the medium pH range of 4.0-7.5 are
      studied. The results reveal that, as the pH changes from 7.5 to the isoelectric
      pH, His6, His13, and His14 are protonated in turn, successively approach the
      center of mass of folded Abeta monomer, trigger ionic interactions and changes of
      neighboring turns (Asp7-Ser8, His14-Lys16) and even a distant one (Leu34-Met35),
      as well as concomitant changes of secondary structure, and promote the
      conformation transition from unfolded to folded. This observation discloses that
      protonation can convert these charged residues from originally hydrophilic to
      "hydrophobic-like". For fibril-like oligomers, the pH susceptibility essentially
      stems from the pK values of charged residues in the context of the Abeta fibril,
      and in turn one can predict the dynamic behavior of these residues in the
      processes of dissociation or stabilization of a fibril by comparing the pK values
      of residues involved in salt bridges in the normal state with those in the
      current context. This idea is justified by two fibril models and appears to be
      applicable to other peptides and their fibril systems.

PMID- 29380496
TI  - Selective Reductive Elimination at Alkyl Palladium(IV) by Dissociative Ligand
      Ionization: Catalytic C(sp3 )-H Amination to Azetidines.
AB  - A palladium(II)-catalyzed gamma-C-H amination of cyclic alkyl amines to deliver
      highly substituted azetidines is reported. The use of a benziodoxole tosylate
      oxidant in combination with AgOAc was found to be crucial for controlling a
      selective reductive elimination pathway to the azetidines. The process is
      tolerant of a range of functional groups, including structural features derived
      from chiral alpha-amino alcohols, and leads to the diastereoselective formation
      of enantiopure azetidines.

PMID- 29380495
TI  - Characterizing the distinct structural changes associated with self-reported knee
      injury among individuals with incident knee osteoarthritis: Data from the
      osteoarthritis initiative.
AB  - We aimed to characterize the agreement between distinct structural changes on
      magnetic resonance (MR) imaging and self-reported injury in the 12 months leading
      to incident common or accelerated knee osteoarthritis (KOA). We conducted a
      descriptive study using data from baseline and the first 4 annual visits of the
      Osteoarthritis Initiative. Knees had no radiographic KOA at baseline (Kellgren
      Lawrence [KL]<2). We classified two groups: (1) accelerated KOA: a knee developed
      advanced-stage KOA (KL = 3 or 4) within 48 months and (2) common KOA: a knee
      increased in radiographic severity (excluding those with accelerated KOA). Adults
      were 1:1 matched based on sex. The index visit was when a person met the
      accelerated or common KOA criteria. We limited our sample to people with MR
      images and self-reported injury data at index visit and year prior. Among 226
      people, we found fair agreement between self-reported injuries and distinct
      structural changes (kappa = 0.24 to 0.31). Most distinct structural changes were
      medial meniscal pathology. No distinct structural changes (e.g., root or radial
      tears) appeared to differ between adults who reported or did not report an
      injury; except, all subchondral fractures occurred in adults who developed
      accelerated KOA and reported an injury. While there is fair agreement between
      self-reported knee injuries and distinct structural changes, there is some
      discordance. Self-reported injury may represent a different construct from
      distinct structural changes that occur after joint trauma. Clin. Anat. 31:330
      334, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29380497
TI  - Preterm premature rupture of membranes is a collateral effect of improvement in
      perinatal outcomes following fetoscopic coagulation of chorionic vessels for twin
      twin transfusion syndrome: a retrospective observational study of 1092 cases.
AB  - OBJECTIVES: Preterm premature rupture of membranes (PPROM) is a leading
      complication following fetoscopic laser coagulation (FLC) for twin-twin
      transfusion syndrome (TTTS). Our primary objective was to describe the impact of
      improvements in surgical technique on survival and rate of PPROM over time. The
      secondary objective was to assess potential risk factors for PPROM. DESIGN AND
      SETTING: Single-centre retrospective observational study. POPULATION: 1092
      consecutive cases of TTTS operated by FLC between 2000 and 2016, with a 6.8% rate
      of loss to follow up. METHODS: The incidence of PPROM and potential risk factors
      were analysed using competing risks models. MAIN OUTCOME MEASURES: PPROM,
      neonatal survival and neurological damage at 28 days. RESULTS: PPROM <32 weeks
      increased from 15 to 40% between 2000 and 2016 along with an overall improvement
      of perinatal outcomes: dual survival rose from 42 to 66% whereas dual losses
      dropped two-fold, from 19 to 9%. Gestational age at surgery at <17 weeks was a
      significant risk-factor for PPROM, with an additional risk of 10% within the
      first week of surgery. Although early PPROM at <20 weeks carried a 56% risk of
      miscarriage, the occurrence of PPROM at >20 weeks did not affect survival,
      despite an increase in preterm birth at <32 weeks. CONCLUSIONS: With significant
      improvement in perinatal outcomes, possibly related to improvements in surgical
      technique, postoperative complications have shifted to non-lethal obstetric
      complications such as PPROM, with rather reassuring postnatal outcomes, despite
      an increase in preterm birth and, potentially, morbidity. Early surgeries (<17
      weeks) are at higher risk of postoperative PPROM. TWEETABLE ABSTRACT: Following
      laser/TTTS, rates of PPROM increased with perinatal survival; surgeries at <17
      weeks are at highest risk.

PMID- 29380498
TI  - An outbreak of acute hepatitis A among young adult men: clinical features and HIV
      coinfection rate from a large teaching hospital in Rome, Italy.
AB  - OBJECTIVES: Italy is a low-incidence region for hepatitis A; however, during the
      last 2 years an increase in the incidence of hepatitis A virus (HAV) infection
      was reported in Europe. The aim of this study was to describe this recent
      outbreak. METHODS: We retrospectively analysed all cases of acute hepatitis A
      diagnosed at our laboratory between January 2010 and June 2017. We evaluated the
      following variables at the time of diagnosis: sex, age, nationality, glutamic
      oxaloacetic transaminase (GOT/AST), glutamic pyruvic transaminase (GPT/ALT),
      bilirubin concentration, international normalized ratio (INR) and the presence or
      absence of anti-HIV-1/2 antibodies. Hospitalization was also considered. We
      analysed these parameters using the chi2 test and Mann-Whitney U-test. RESULTS: A
      total of 225 cases were analysed; 82.7% were in male patients, 94.2% were in
      Italians and the median age of the patients was 36.4 years. At diagnosis, the
      median GOT value was 306 U/L, the median GPT was 1389 U/L, and the median total
      bilirubin value was 5.88 mg/dL. Hospitalization was required for 142 patients,
      with a median duration of hospital stay of 8.5 days. In 2016-2017 we registered
      141 cases, with a higher prevalence of male patients, higher GPT values and a
      higher prevalence of patients aged 20-39 years compared with older (2010-2015)
      cases. Homosexual intercourse was reported as the HAV risk factor in 70.2% of
      patients. HIV serology was available for 120 patients: 24 were HIV-positive, four
      of whom represented new diagnoses. HIV-positive patients showed lower bilirubin
      and GPT values and fewer hospitalizations than HIV-negative patients.
      CONCLUSIONS: In 2016-2017, we saw a rise in the number of hepatitis A cases, with
      a higher prevalence of adult male patients. No significant differences regarding
      the prevalence of HIV coinfection emerged.

PMID- 29380499
TI  - Removal of vancomycin administered during dialysis by a high-flux dialyzer.
AB  - INTRODUCTION: Hemodialysis patients frequently receive vancomycin for treatment
      of gram-positive bacterial infections. This drug is most conveniently
      administered in outpatient dialysis units during the hemodialysis treatment.
      However, there is a paucity of data on the removal of vancomycin by high-flux
      polyamide dialyzers. METHODS: This is a prospective crossover study in which
      seven uninfected chronic hemodialysis patients at three dialysis units received
      vancomycin 1 gram intravenously over one hour immediately after the dialysis
      treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis
      treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high-flux
      (Polyflux 24R) dialyzer (Phase 2). There was a three-week washout period between
      phases. Serial serum vancomycin concentrations were used to determine the removal
      of vancomycin when administered during dialysis. FINDINGS: Dialysis removed 35 +/
      15% (range 18-56%) of the vancomycin dose when administered during the last hour
      of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0
      44.5 hours from the start of infusion were similar between the two phases
      (AUCPhase 1 884 +/- 124 mg-hr/L, mean +/- SD; AUCPhase 2 856 +/- 208 mg-hr/L;
      P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis
      treatment following vancomycin administration were also similar between the two
      phases (13.1 +/- 2.7 mg/L in Phase 1 and 12.3 +/- 3.3 mg/L in Phase 2; P=0.55).
      DISCUSSION: When using a polyarylethersulfone, polyvinylpyrrolidone, and
      polyamide high-flux HD membrane with a 24R Polyflux dialyzer, vancomycin can be
      administered during the last hour of dialysis if the dose that is prescribed for
      intra-dialysis dosing is empirically increased to account for intra-dialytic drug
      removal.

PMID- 29380500
TI  - Validation and standardization of the Brazilian version of the Medication Regimen
      Complexity Index for older adults in primary care.
AB  - AIM: To validate and standardize the Brazilian version of the Medication Regimen
      Complexity Index (MRCI) for older adults in primary healthcare. METHODS: A cross
      sectional methodological study was carried out with elderly patients attending
      primary healthcare centers in southeastern Brazil. Convergent validity was tested
      by correlating MRCI scores with medication number. Divergent validity was tested
      by correlating MRCI scores with age, sex, cognition, and basic and instrumental
      activities of daily living. Reliability was assessed by interrater and test
      retest reliability. Regarding standardization, percentiles were calculated for
      the total MRCI scores. RESULTS: A total of 227 older adults were included, with a
      mean age of 71.4 years (standard deviation 7.5 years) and mostly women (70.9%).
      There was a correlation between MRCI scores and medication number (rho = 0.890; P
      = 0.000). There was no correlation between MRCI scores and age (P = 0.192), sex
      (P = 0.052), cognition (P = 0.369), and basic (P = 0.682) and instrumental (P =
      0.582) activities of daily living. High interrater (intraclass correlation
      coefficient = 0.98; rho = 0.991) and test-retest (intraclass correlation
      coefficient = 0.996; rho = 0.985) reliability was obtained. The following
      complexity was considered: low, MRCI <= 9.0 points; average 0.9 < MRCI <= 16.5
      points; and high, MRCI > 16.5 points. CONCLUSIONS: MRCI showed satisfactory
      psychometric qualities for measuring regimen complexity of older adults attending
      the primary healthcare centers evaluated. Standardization might increase the
      applicability of MRCI to the health research context. Geriatr Gerontol Int 2018;
      18: 853-859.

PMID- 29380501
TI  - Dynamic Interconversion between Boroxine Cages Based on Pyridine Ligation.
AB  - Dynamic interconversion between large covalent organic cages was achieved simply
      by heating or acid/base treatment. A mixture of the boroxine cages 12-mer and 15
      mer was cleanly converted into a pyridine adduct of the 9-mer boroxine cage upon
      treatment with pyridine, and the geometry of N-coordinated boron atoms changed
      from trigonal to tetrahedral. The reverse reaction was achieved by heating or
      acid treatment. In this process, the larger boroxine cages 12-mer and 15-mer were
      found to be entropically favored owing to the release of free pyridine molecules
      from 9-mer?6 Py.

PMID- 29380502
TI  - Development and validation of the canine visual function instrument.
AB  - OBJECTIVE: In this study, we created the Canine Visual Function Instrument (CVFI)
      and tested its validity and reliability for assessing the quality of vision of
      dogs. METHODS: We used Cronbach's alpha to test the strength of the consistency
      of the questions in the instrument and factor analysis to assess whether the
      questions achieved unidimensionality in the measurement of dogs' vision quality.
      RESULTS: Our analysis shows that the CVFI is a valid and reliable tool to seek
      self-reported observations about dogs' vision quality from owners. Our results
      also show that the vision quality scale has high empirical validity and therefore
      can be used to determine whether a dog has normal vision or moderate or serious
      visual impairments. CONCLUSION: The CVFI might have important practical
      applications in the field of veterinary ophthalmology in two important ways.
      First, it can be used to determine whether the treatment of dogs with visual
      impairment improves vision quality. Second, it can be used as a warning system to
      alert owners about their dogs' quality of vision.

PMID- 29380503
TI  - Oral function as an indexing parameter for mild cognitive impairment in older
      adults.
AB  - AIM: To investigate the association between mild cognitive impairment (MCI) and
      oral status, and to develop an oral-based screening index for MCI. METHODS: A
      cross-sectional study was carried out in a total of 5104 community-dwelling
      adults (aged >=65 years) from the Obu Study of Health Promotion for the Elderly.
      Screening for MCI included a standardized personal interview, Mini-Mental State
      Examination, Geriatrics and Gerontology-Functional Assessment Tool (which
      included 8 tasks used to assess logical memory, word list memory, attention and
      executive function, processing speed, and visuospatial skill) and oral status.
      RESULTS: In our study, 930 individuals were diagnosed with MCI, whereas the
      remaining 2669 were not. Both men and women with MCI showed a significantly lower
      number of functional and present teeth, poorer oral diadochokinesis, and less
      palpation of masseter muscle tension (P < 0.01). Discriminant analysis of
      participants with MCI, between categories of pertinence and non-pertinence,
      showed significant associations for age, sex, educational background, handgrip
      strength, Geriatric Depression Scale score, Mini-Mental State Examination score,
      history of heart disease, albumin level and oral diadochokinesis representing
      oral motor skill. Although the diagnosis rate of our screening index for MCI was
      not high, it was in the acceptable range as a screening index. CONCLUSIONS: Oral
      motor skill, such as lip movement, might be impaired in patients with MCI.
      Detecting decreasing oral motor dexterity supports the early detection of MCI,
      and might be key to improve the prognosis of dementia. Geriatr Gerontol Int 2018;
      18: 790-798.

PMID- 29380504
TI  - Quasi-static strength and fractography analysis of two dental implants
      manufactured by direct metal laser sintering.
AB  - BACKGROUND: New manufacturing methods was developed to improve the tissues
      integration with the titanium alloy pieces. OBJECTIVE: The present in vitro study
      was to assess the resistance and fracture mode after applied a quasi-static
      compressive force on the two dental implants manufactured by direct metal laser
      sintering. MATERIALS AND METHODS: Twenty dental implants manufactured by direct
      metal laser sintering, using titanium alloy (Ti-6Al-4V) granules in two designs
      (n = 10 per group): Conventional dental implant (group Imp1) two-piece implant
      design, where the surgical implant and prosthetic abutment are two separate
      components and, the one-piece implant (group Imp2), where the surgical implant
      and prosthetic abutment are one integral piece. All samples were subjected to
      quasi-static loading at a 30 degrees  angle to the implant axis in a universal
      testing machine. RESULTS: The mean fracture strengths were 1269.2 +/- 128.8 N for
      the group Imp1 and, 1259.5 +/- 115.1 N for the group Imp2, without statistical
      differences (P = .8722). In both groups, the fracture surface does not present
      crack between the compact core and the superficial (less dense and porous) part
      of the implants. CONCLUSIONS: Based on the measured resistance data for the two
      implant models manufactured by direct metal laser sintering tested in the present
      study, we can suggest that they have adequate capacity to withstand the
      masticatory loads.

PMID- 29380505
TI  - Tandem Radical Cyclization for the Construction of Difluoro-Containing Oxindoles
      and Quinoline-2,4-diones.
AB  - Cu-catalyzed direct difluoromethylation of activated alkenes through a
      difluoromethyl radical addition/cyclization to afford difluorinated oxindoles and
      quinoline-2,4-diones has been developed. This method provides convenient access
      to a variety of oxindoles and quinoline-2,4-diones under mild conditions via a
      proposed tandem radical cyclization process, while tolerating various functional
      groups well. Moreover, a facile method to construct diverse difluorinated
      quinoline-2,4-diones by visible-light photoredox catalysis under mild conditions
      was presented.

PMID- 29380506
TI  - Sulfur isotope's signal of nanopyrites enclosed in 2.7 Ga stromatolitic organic
      remains reveal microbial sulfate reduction.
AB  - Microbial sulfate reduction (MSR) is thought to have operated very early on Earth
      and is often invoked to explain the occurrence of sedimentary sulfides in the
      rock record. Sedimentary sulfides can also form from sulfides produced
      abiotically during late diagenesis or metamorphism. As both biotic and abiotic
      processes contribute to the bulk of sedimentary sulfides, tracing back the
      original microbial signature from the earliest Earth record is challenging. We
      present in situ sulfur isotope data from nanopyrites occurring in carbonaceous
      remains lining the domical shape of stromatolite knobs of the 2.7-Gyr-old
      Tumbiana Formation (Western Australia). The analyzed nanopyrites show a large
      range of delta34 S values of about 840/00 (from -33.70/00 to +50.40/00). The
      recognition that a large delta34 S range of 800/00 is found in individual
      carbonaceous-rich layers support the interpretation that the nanopyrites were
      formed in microbial mats through MSR by a Rayleigh distillation process during
      early diagenesis. An active microbial cycling of sulfur during formation of the
      stromatolite may have facilitated the mixing of different sulfur pools
      (atmospheric and hydrothermal) and explain the weak mass independent signature
      (MIF-S) recorded in the Tumbiana Formation. These results confirm that MSR
      participated actively to the biogeochemical cycling of sulfur during the
      Neoarchean and support previous models suggesting anaerobic oxidation of methane
      using sulfate in the Tumbiana environment.

PMID- 29380507
TI  - Exposure of helices alpha4 and alpha5 is required for insecticidal activity of
      Cry2Ab by promoting assembly of a prepore oligomeric structure.
AB  - Cry2Ab, a pore-forming toxin derived from Bacillus thuringiensis, is widely used
      as a bio-insecticide to control lepidopteran pests around the world. A previous
      study revealed that proteolytic activation of Cry2Ab by Plutella xylostella
      midgut juice was essential for its insecticidal activity against P. xylostella,
      although the exact molecular mechanism remained unknown. Here, we demonstrated
      for the first time that proteolysis of Cry2Ab uncovered an active region (the
      helices alpha4 and alpha5 in Domain I), which was required for the mode of action
      of Cry2Ab. Either the masking or the removal of helices alpha4 and alpha5
      mediated the pesticidal activity of Cry2Ab. The exposure of helices alpha4 and
      alpha5 did not facilitate the binding of Cry2Ab to P. xylostella midgut receptors
      but did induce Cry2Ab monomer to aggregate and assemble a 250-kDa prepore
      oligomer. Site-directed mutagenesis assay was performed to generate Cry2Ab
      mutants site directed on the helices alpha4 and alpha5, and bioassays suggested
      that some Cry2Ab variants that could not form oligomers had significantly lowered
      their toxicities against P. xylostella. Taken together, our data highlight the
      importance of helices alpha4 and alpha5 in the mode of action of Cry2Ab and could
      lead to more detailed studies on the insecticidal activity of Cry2Ab.

PMID- 29380508
TI  - Pneumonia risks in bedridden patients receiving oral care and their screening
      tool: Malnutrition and urinary tract infection-induced inflammation.
AB  - AIM: Pneumonia develops in bedridden patients even when they are receiving oral
      care. However, the pneumonia risk in bedridden patients remains unclear, and no
      screening tool has been developed to assess this risk by using daily hospital
      data. METHODS: We retrospectively examined pneumonia risk factors by analyzing
      the records of 102 bedridden patients receiving oral care. RESULTS: Body mass
      index, peripheral blood hemoglobin, and serum concentrations of total protein,
      albumin, total cholesterol and uric acid in the pneumonia group (n = 51; mean age
      73.4 years) were lower than those in the non-pneumonia group (n = 51; mean age
      68.1 years). In the univariate analysis, body mass index; leukocytosis; high C
      reactive protein; low levels of hemoglobin, total protein and albumin (<3.5
      g/dL); and urine bacteria were associated with the development of pneumonia.
      Furthermore, in the multivariate analysis, low levels of albumin and urine
      bacteria were independently associated with pneumonia. We developed a bedridden
      patient pneumonia risk (BPPR) score using these two risk factors to assess
      pneumonia risk. We applied scores of zero (0) or one (1) according to the absence
      or presence of the two risk factors and summed the scores in each patient. The
      proportion of pneumonia patients increased with increasing BPPR score when the
      patients were divided into three groups - low, moderate and high risk - according
      to the BPPR score (0, 1 or 2, respectively). CONCLUSIONS: Malnutrition, urinary
      tract infection-induced inflammation and anemia were associated with pneumonia in
      bedridden patients. BPPR scoring might be useful for assessing pneumonia risk and
      managing affected patients. Geriatr Gerontol Int 2018; 18: 714-722.

PMID- 29380509
TI  - Zirconium-Porphyrin-Based Metal-Organic Framework Hollow Nanotubes for
      Immobilization of Noble-Metal Single Atoms.
AB  - Single atoms immobilized on metal-organic frameworks (MOFs) with unique
      nanostructures have drawn tremendous attention in the application of catalysis
      but remain a great challenge. Various single noble-metal atoms have now been
      successfully anchored on the well-defined anchoring sites of the zirconium
      porphyrin MOF hollow nanotubes, which are probed by aberration-corrected scanning
      transmission electron microscopy and synchrotron-radiation-based X-ray absorption
      fine-structure spectroscopy. Owing to the hollow structure and excellent
      photoelectrochemical performance, the HNTM-Ir/Pt exhibits outstanding catalytic
      activity in the visible-light photocatalytic H2 evolution via water splitting.
      The single atom immobilized on MOFs with hollow structures are expected to pave
      the way to expand the potential applications of MOFs.

PMID- 29380510
TI  - Bone and soft tissue outcomes, risk factors, and complications of implant
      supported prostheses: 5-Years RCT with different abutment types and loading
      protocols.
AB  - BACKGROUND: Data on risk factors and complications after long-term implant
      treatment is limited. The aims were to evaluate the role of various fixation
      modes and to analyze complications and risks that affect long-term use of implant
      supported partial fixed dental prostheses. MATERIALS AND METHODS: Fifty partially
      edentulous subjects received three Branemark TiUniteTM implants. Superstructures
      were attached directly at implant level (IL) or via abutments: machined surface
      (AM) and an oxidized surface (AOX, TiUniteTM). Implants were immediately loaded
      (test) or unloaded for 3 months (control). Examinations occurred over a 5-year
      period. RESULTS: Forty-four subjects were re-examined after 5 years. Cumulative
      survival rates in test and control groups were 93.9% and 97.0%, respectively.
      Marginal bone loss (MBL; Mean [SEM]) was significantly lower at superstructures
      connected to AM (1.61 [0.25] mm) than at sites with no abutment IL (2.14 [0.17]
      mm). Peri-implantitis occurred in 9.1% of subjects and in 4.0% of implants.
      Multiple linear regression indicated that increased probing pocket depth (PPD),
      periodontal disease experience, deteriorating health, and light smoking (<=10
      cigarettes/day) predict greater MBL, whereas increased buccal soft tissue
      thickness and higher ISQ predict lower MBL. CONCLUSIONS: The results show that
      MBL was influenced by the connection type. A machined abutment, instead of
      connecting the superstructure directly at the implant level, was beneficial. The
      following factors influenced MBL: PPD, periodontal disease experience,
      deteriorating health, light smoking, buccal soft tissue thickness, and ISQ. The
      results on peri-implantitis underscore the need for long-term maintenance care.
      Further, the abutment material surface properties constitute additional target
      for strategies to minimize MBL.

PMID- 29380511
TI  - Content analysis of consumer information about knee arthroscopy in Australia.
AB  - BACKGROUND: Despite the availability of consistent guidelines recommending
      against arthroscopic treatment for people with symptomatic knee osteoarthritis,
      Australian data indicate continued use of this treatment modality. A paucity of
      easy to understand and reliable consumer information about knee arthroscopy may
      be one explanatory factor. The aim of this study was to determine whether
      consumer information about knee arthroscopy available in Australia is adequate to
      inform evidence-based decision-making for people with symptomatic osteoarthritis.
      METHODS: We performed a content analysis of consumer information about knee
      arthroscopy for symptomatic osteoarthritis. Information sources were identified
      from the Australian Commission on Quality and Safety in Health Care and Internet
      searches conducted 20-28 May 2015. Search terms were 'knee arthroscopy', 'knee
      pain', 'osteoarthritis knee' and 'meniscal tear', and 'orthopaedic surgeon'
      linked to each Australian capital city. Two independent reviewers selected
      documents for inclusion and extracted data. Main outcomes were specific advice
      regarding use of arthroscopic treatment for people with knee osteoarthritis,
      mention of guidelines, and/or supporting evidence. RESULTS: Ninety-three
      documents were analyzed (44 were a paragraph or less). Only eight made a clear
      recommendation against use of arthroscopy for all/most people with knee
      osteoarthritis. None included an explicit statement attributed to a guideline,
      while only six provided any research evidence to support their advice. Wikipedia
      provided the most valid information but it may be incomprehensible to the average
      reader. CONCLUSION: Currently available consumer information about knee
      arthroscopy in Australia may be inadequate to help people with symptomatic knee
      osteoarthritis make informed decisions about this treatment.

PMID- 29380512
TI  - An experimental and numerical study on tactile neuroimaging: A novel minimally
      invasive technique for intraoperative brain imaging.
AB  - BACKGROUND: The success of tumour neurosurgery is highly dependent on the ability
      to accurately localize the operative target, which may shift during the
      operation. Performing intraoperative brain imaging is crucial in minimally
      invasive neurosurgery to detect the effect of brain shift on the tumour's
      location, and to maximize the efficiency of tumour resection. METHOD: The major
      objective of this research is to introduce tactile neuroimaging as a novel
      minimally invasive technique for intraoperative brain imaging. To investigate the
      feasibility of the proposed method, an experimental and numerical study was first
      performed on silicone phantoms mimicking the brain tissue with a tumour. Then the
      study was extended to a clinical model with the meningioma tumour. RESULTS: The
      stress distribution on the brain surface has high potential to intraoperatively
      localize the tumour. CONCLUSION: Results suggest that tactile neuroimaging can be
      used to provide non-invasive and real-time intraoperative data on a tumour's
      features.

PMID- 29380513
TI  - A novel cell line generated using the CRISPR/Cas9 technology as universal quality
      control material for KRAS G12V mutation testing.
AB  - BACKGROUND: KRAS mutations are the key indicator for EGFR monoclonal antibody
      targeted therapy and acquired drug resistance, and their accurate detection is
      critical to the clinical decision-making of colorectal cancer. However, no proper
      quality control material is available for the current detection methods,
      particularly next-generation sequencing (NGS). The ideal quality control material
      for NGS needs to provide both the tumor mutation gene and the matched background
      genomic DNA, which is uncataloged in public databases, to accurately distinguish
      germline polymorphisms and somatic mutations. METHODS: We developed a novel KRAS
      G12V mutant cell line using the clustered regularly interspaced short palindromic
      repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technique to make up for the
      deficiencies in existing quality control material and further validated the
      feasibility of the cell line as quality control material by amplification
      refractory mutation system (ARMS), Sanger sequencing, digital PCR (dPCR), and
      NGS. RESULTS: We verified that the edited cell line specifically had the G12V
      mutation, and the validation results presented a high consistency among the four
      methods of detection. The three cell lines screened contained the G12V mutation
      and the mutation allele fractions of G12V-1, G12V-2, and G12V-3 were 52.01%,
      82.06%, and 17.29%, respectively. CONCLUSION: The novel KRAS G12V cell line
      generated using the CRISPR/Cas9 gene editing system is suitable as a quality
      control material for all current detection methods and provides a new direction
      in the development of quality control material.

PMID- 29380514
TI  - High-Purity Inorganic Perovskite Films for Solar Cells with 9.72 % Efficiency.
AB  - All-inorganic perovskite solar cells with high efficiency and improved stability
      are promising for commercialization. A multistep solution-processing method was
      developed to fabricate high-purity inorganic CsPbBr3 perovskite films for use in
      efficient solar cells. By tuning the number of deposition cycles (n) of a CsBr
      solution, the phase conversion from CsPb2 Br5 (n <=3), to CsPbBr3 (n=4), and Cs4
      PbBr6 (n>=5) was optimized to achieve vertical- and monolayer-aligned grains.
      Upon interfacial modification with graphene quantum dots, the all-inorganic
      perovskite solar cell (without a hole-transporting layer) achieved a power
      conversion efficiency (PCE) as high as 9.72 % under standard solar illumination
      conditions. Under challenging conditions, such as 90 % relative humidity (RH) at
      25  degrees C or 80  degrees C at zero humidity, the optimized device retained 87
      % PCE over 130 days or 95 % over 40 days, compared to the initial efficiency.

PMID- 29380515
TI  - Acute hemodialysis in a young man with severe symptomatic hyponatremia and kidney
      injury.
AB  - A 35-year-old man presented with severe hypo-osmolar hyponatremia (serum sodium
      99 mmol/L), profound nonoliguric renal failure (serum creatinine 1240 MUmol/L),
      and nephrotic range proteinuria. Computed tomography of the abdomen revealed
      nephromegaly and no obstruction. The patient was admitted to the intensive care
      unit (ICU) and conventional hemodialysis was initiated. To avoid rapid sodium
      correction, we prescribed concurrent dialysate flow, a low dialysate sodium
      concentration, a small surface area dialyzer, and a low blood flow rate. We
      infused dextrose 5% water into the venous return line and adjusted the infusion
      rate according to hourly sodium concentration. The rate of sodium correction was
      7.7 mmol/day over the first 3 days of admission. A subsequent renal biopsy
      revealed focal segmental glomerulosclerosis and interstitial infiltration with
      extranodal NK/T-cell lymphoma nasal type. The patient died of massive lower
      gastrointestinal bleeding secondary to lymphomatous involvement day 19 in the
      ICU. In the setting of acute kidney injury requiring renal replacement therapy
      and concomitant severe hyponatremia, it is challenging to avoid overcorrection of
      serum sodium. We describe several key prescription modifications to conventional
      hemodialysis, factors that affect sodium diffusion at the level of the dialyzer
      membrane, and the importance of frequent laboratory monitoring.

PMID- 29380517
TI  - Therapeutic efficacy of low-dose (25 mg) mirabegron therapy for patients with
      mild to moderate overactive bladder symptoms due to central nervous system
      diseases.
AB  - OBJECTIVE: The incidence of overactive bladder (OAB) increases with age,
      especially in patients with central nervous system (CNS) disorders such as
      cerebrovascular accident (CVA) and Parkinson's disease (PD). Mirabegron is a
      novel medication for the treatment of OAB. The present study investigated the
      therapeutic effect of mirabegron on OAB patients with CNS diseases. METHODS:
      Patients with CVA, PD, dementia, and OAB symptoms were consecutively enrolled in
      the study group, and mirabegron 25 mg q.d. was prescribed. Clinical effects,
      evaluated using the Overactive Bladder Symptom Score (OABSS), Urinary Sensation
      Scale (USS), International Prostate Symptom Score (IPSS), and Patient Perception
      of Bladder Condition (PPBC), as well as urodynamic parameters and adverse events
      were assessed at baseline and 4 and 12 weeks after treatment. RESULTS: In all, 44
      patients (mean [+/- SD] age 77.7 +/- 9.49 years) with OAB due to CVA (n = 27), PD
      (n = 6), and dementia (n = 11) were included in the present prospective study.
      Mirabegron resulted in significant improvements in symptom scores on the OABSS (P
      = .02), USS (P = .009), total IPSS (P = .002), Storage and Voiding domains of the
      IPSS (P = .001 and .017, respectively), and PPBC (P = .001). No significant
      changes were noted in post-void residual, maximum flow rate, and voided volume
      after treatment. Only 5 patients dropped out due to poor therapeutic efficacy and
      shifted to antimuscarinics. Three patients complained of adverse effects,
      including dizziness and dysuria. No patient complained of urine retention or
      constipation. CONCLUSION: Mirabegron 25 mg once daily effectively decreased
      urgency symptoms in elderly OAB patients with CNS lesions after the 12-week
      treatment period. The adverse events were mild and only noted in a few cases.

PMID- 29380518
TI  - Ocular anatomy of the black pacu (Colossoma macropomum): gross, histologic, and
      diagnostic imaging.
AB  - OBJECTIVE: To describe the ocular anatomy of the black pacu (Colossoma
      macropomum), a freshwater teleost fish of the Amazon River basin, including an
      unusual choroid laden with adipose tissue. PROCEDURES: Three adult black pacu
      were anesthetized and examined clinically and with ocular ultrasonography, then
      euthanized. Three fish were euthanized and their heads imaged immediately
      postmortem using computed tomography. One fish was euthanized and its exenterated
      eyes imaged by high-resolution magnetic resonance imaging. The exenterated eyes
      of all seven fish were fixed in formalin; eyes from three fish were examined
      grossly and histologically. Additionally, archived histologic sections from two
      smaller black pacu specimens were examined. RESULTS: Findings were consistent
      among the ocular imaging modalities used. Intrinsic to the sclera were
      circumferential ossicles and scleral cartilage. The lens was spherical and
      protruded through the ovoid pupil with an aphakic space inferiorly when the
      accommodative mechanism was relaxed under anesthesia. Both a small falciform
      process and epiretinal vasculature were present in the posterior segment. The
      retina was cone-rich, and processes of the retinal pigment epithelium enveloped
      the photoreceptor outer segments. Remarkably, the choroid occupied one-third of
      the anteroposterior length of the globe; histology confirmed that the bulk of the
      choroid was composed of adipose tissue. CONCLUSIONS: The eye of the pacu overall
      is typical of teleosts but has the notable and consistent finding of a
      substantive store of choroidal fat of unknown function.

PMID- 29380516
TI  - Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a
      BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib.
AB  - Efficacy of BRAF V600E targeted therapies in brain tumors harboring the mutation
      has been shown in several case reports and is currently being studied in larger
      clinical trials. Monotherapy with vemurafenib has been associated with
      significant side effects, including rashes, papillomas, and squamous cell
      carcinomas. Here we describe an adolescent female with anaplastic ganglioglioma
      and significant skin reaction to vemurafenib with subsequent tumor response and
      tolerance to the BRAF/MEK inhibitor combination of dabrafenib and trametinib
      without recurrence of previous reaction.

PMID- 29380520
TI  - Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic
      dysregulation associated with neuroblastoma.

PMID- 29380519
TI  - Development of Pseudomonas aeruginosa Lectin LecA Inhibitor by using Bivalent
      Galactosides Supported on Polyproline Peptide Scaffolds.
AB  - LecA is a galactose-binding tetrameric lectin from Pseudomonas aeruginosa
      involved in infection and biofilm formation. The emergent antibiotic resistance
      of P. aeruginosa has made LecA a promising pharmaceutical target to treat such
      infections. To develop LecA inhibitors, we exploit the unique helical structure
      of polyproline peptides to create a scaffold that controls the galactoside
      positions to fit their binding sites on LecA. With a modular scaffold design,
      both the galactoside ligands and the inter-ligand distance can be altered
      conveniently. We prepared scaffolds with spacings of 9, 18, 27, and 36 A for
      ligand conjugation and found that glycopeptides with galactosides ligands three
      helical turns (27 A) apart best fit LecA. In addition, we tested different
      galactose derivatives on the selected scaffold (27 A) to improve the binding
      avidity to LecA. The results validate a new multivalent scaffold design and
      provide useful information for LecA inhibitor development.

PMID- 29380521
TI  - Treatment of a pediatric patient with MET-amplified signet ring cell
      adenocarcinoma of the stomach with crizotinib.

PMID- 29380522
TI  - Synthesis and Photocatalytic Application of Stable Lead-Free Cs2 AgBiBr6
      Perovskite Nanocrystals.
AB  - Lead halide perovskite nanocrystals (NCs) have demonstrated great potential as
      appealing candidates for advanced optoelectronic applications. However, the
      toxicity of lead and the intrinsic instability toward moisture hinder their mass
      production and commercialization. Herein, to solve such thorny problems, novel
      lead-free Cs2 AgBiBr6 double perovskite NCs fabricated via a simple hot-injection
      method are reported, which exhibit impressive stability in moisture, light, and
      temperature. Such materials are then applied into photocatalytic CO2 reduction,
      achieving a total electron consumption of 105 umol g-1 under AM 1.5G illumination
      for 6 h. This study offers a reliable avenue for Cs2 AgBiBr6 perovskite
      nanocrystals preparation, which holds a great potential in the further
      photochemical applications.

PMID- 29380523
TI  - DCD donor hemodynamics as predictor of outcome after kidney transplantation.
AB  - Insufficient hemodynamics during agonal phase-ie, the period between withdrawal
      of life-sustaining treatment and circulatory arrest-in Maastricht category III
      circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion
      injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted
      between 2006 and 2014. Peripheral oxygen saturation (SpO2-with pulse oximetry at
      the fingertip) and systolic blood pressure (SBP-with arterial catheter) were
      measured during agonal phase, and were dichotomized into minutes of SpO2 > 60% or
      SpO2 < 60%, and minutes of SBP > 80 mmHg or SBP < 80 mmHg. Outcome measures were
      and primary non-function (PNF), delayed graft function (DGF), and three-year
      graft survival. Primary non-function (PNF) rate was 6.6%, delayed graft function
      (DGF) rate was 67%, and graft survival at three years was 76%. Longer periods of
      agonal phase (median 16 min [IQR 11-23]) contributed significantly to an
      increased risk of DGF (P = .012), but not to PNF (P = .071) and graft failure (P
      = .528). Multiple logistic regression analysis showed that an increase from 7 to
      20 minutes in period of SBP < 80 mmHg was associated with 2.19 times the odds
      (95% CI 1.08-4.46, P = .030) for DGF. In conclusion, duration of agonal phase is
      associated with early transplant outcome. SBP < 80 mmHg during agonal phase shows
      a better discrimination for transplant outcome than SpO2 < 60% does.

PMID- 29380524
TI  - Noninvasive encapsulated follicular variant of papillary thyroid carcinoma:
      Should it also be reclassified in children?
AB  - BACKGROUND: Noninvasive encapsulated follicular variant of papillary thyroid
      carcinoma (noniEFVPTC) has low risk of adverse outcome in adults, warranting
      reclassification as noninvasive follicular thyroid neoplasm with papillary-like
      nuclear features (NIFTP). In children, thyroid nodules have higher risk of
      malignancy and it is unknown if encapsulated FVPTC (EFVPTC) and infiltrative
      FVPTC (IFVPTC) tumors have different behavior. We analyzed the clinicopathologic
      features of follicular variant of papillary thyroid carcinoma (FVPTC) subtypes in
      our pediatric population to determine if noniEFVPTC has an indolent course as
      reported in adults. PROCEDURE: We retrospectively studied all patients diagnosed
      with FVPTC at our institution. The clinicopathologic characteristics of the
      histologic subtypes were compared. RESULTS: Eighteen patients were identified,
      all treated with total thyroidectomy. No significant differences in age, sex,
      tumor size, focality, or prior malignancy were detected between subtypes.
      Extrathyroidal extension had significantly higher incidence in IFVPTC (5/8)
      compared with EFVPTC (1/10, P = 0.03), translating in significantly more T3
      tumors within IFVPTC subtype (5/8), whereas most EFVPTC cases had T1 staging
      (6/10, T1 vs. T3, P = 0.05). EFVPTC had significantly lower rate of lymph node
      involvement (N1 in 2/8) compared with IFVPTC (N1 in 8/8, P = 0.003). Only one
      patient diagnosed with IFVPTC developed extranodal recurrence. When noniEFVPTC
      and iEFVPTC were separately compared, the noninvasive form showed no propensity
      for invasive growth (T3 staging: 0/4 vs. 2/6), lymph node metastasis (N1: 0/3 vs.
      2/5) or extranodal recurrence. CONCLUSION: In children, noniEFVPTC/NIFTP has
      indolent behavior, warranting consideration of less aggressive management,
      similar to adults.

PMID- 29380525
TI  - New practical methods to obtain crucial data in performing diagnostic meta
      analysis of the published literature.
AB  - AIM: Found some new methods that can be used to obtain values such as true
      positives (TP), false negatives (FN), false positives (FP), and true negatives
      (TN) which did not provide in diagnostic meta-analysis indirectly. METHODS: Using
      mathematical deduction and programming calculus. RESULTS: We have succeeded in
      increasing the number of articles that can be used from two(228 patients) to
      five(469 patients) by using our new method. CONCLUSION: Using these methods, it
      can greatly increase the number of the inclusion articles, as well as the number
      of inclusion patients, which will contribute to improve the persuasiveness and
      comprehensiveness of diagnostic meta-analysis.

PMID- 29380526
TI  - Early outcomes and patterns of failure following proton therapy for nonmetastatic
      intracranial nongerminomatous germ cell tumors.
AB  - BACKGROUND: Although dosimetric comparisons demonstrate the advantage of proton
      therapy (PT) over conventional radiotherapy for nongerminomatous germ cell tumors
      (NGGCT), clinical outcome data for this rare tumor are lacking. We sought to
      evaluate outcomes for children with NGGCT treated with PT. METHODS: Between 2007
      and 2016, 14 children (median age 11, range, 5-19 years) with nonmetastatic NGGCT
      were treated with PT after induction chemotherapy. Most (8/14) were mixed germ
      cell. Five of 14 patients had complete resection of their primary tumor before
      radiation. Off study, eight patients received 36 Gy (RBE [relative biological
      effectiveness]) craniospinal irradiation (CSI). On study, two patients received
      30.6 Gy (RBE) whole-ventricle irradiation and four received focal radiation
      alone. All patients received a total dose of 54 Gy (RBE) to the tumor/tumor bed.
      RESULTS: At a median follow-up of 2.8 years, all patients were alive with no
      local recurrences. Three-year progression-free survival was 86%. Both metastatic
      recurrences occurred in patients treated with focal radiation alone; one with an
      immature teratoma developed an isolated spinal recurrence 5 months after
      treatment. Another with a mixed germ cell tumor developed a multifocal
      ventricular and shunt tract recurrence 7 months after treatment. Serious toxicity
      was minimal, including cataracts and hormone deficiency, and limited to children
      who received CSI. CONCLUSION: Early outcomes in children treated for NGGCT
      suggest the high conformality of PT does not compromise disease control and
      yields low toxicity. This pattern of failure data adds to growing evidence
      suggesting chemotherapy followed by focal radiotherapy alone is inadequate in
      controlling localized NGGCT.

PMID- 29380527
TI  - The Sphingosine 1-Phosphate Analogue FTY720 Alleviates Seizure-induced
      Overexpression of P-Glycoprotein in Rat Hippocampus.
AB  - Overexpression of P-glycoprotein (P-gp) in the brain is an important factor
      leading to drug-resistant epilepsy. Clinical use of P-gp inhibitors is limited by
      their systemic toxicity. In this study, we tested the hypothesis that FTY720, a
      sphingosine 1-phosphate (S1P) analogue used for treating multiple sclerosis,
      modulates the up-regulation of P-gp and improves brain delivery of phenytoin
      (PHT) through S1P receptor 1 in the hippocampus of a pilocarpine-induced rat
      model of status epilepticus (SE). We administered vehicle, FTY720 or FTY720+ W146
      (an S1P receptor 1 antagonist) to SE rats. Forty-eight hours after SE, we
      dissected the hippocampus and measured P-gp expression, NF-kappaB activity and
      levels of inflammatory mediators (TNF-alpha and COX-2) by Western blotting and
      enzyme-linked immunosorbent assay. We also measured hippocampal and plasma
      concentrations of PHT 30, 60, 90, 120 and 180 min. after an intraperitoneal
      injection of PHT (50 mg/kg) 48 hr after SE, using microdialysis and high
      performance liquid chromatography. FTY720 alleviated the overexpression of
      hippocampal P-gp in SE rats and reduced NF-kappaB activity and TNF-alpha and COX
      2 expression, and W146 blocked the effects of FTY720. Furthermore, SE rats that
      received FTY720 showed significantly greater hippocampal extracellular PHT
      concentrations than those that received vehicle, and W146 abolished this effect.
      Our results suggest that FTY720 alleviates seizure-induced overexpression of P-gp
      by inhibiting S1P receptor 1-mediated inflammation in rat hippocampus and
      improves PHT delivery to brain. FTY720 shows potential as an adjuvant therapy for
      drug-resistant epilepsy.

PMID- 29380528
TI  - Efficacy of management strategies for aromatase inhibitor-induced arthralgia in
      breast cancer patients: a systematic review.
AB  - Aromatase inhibitors are the gold standard in the treatment of hormone receptor
      positive breast cancer, but lead to an arthralgia syndrome which is implicated in
      13-22% of noncompliance. This is the first systematic review of the efficacy of
      existing management strategies for this side effect. Eligible studies were
      retrieved from computer searches of Medline, Cochrane and Embase and the
      significant intervention groups were identified. The risk of bias of selected
      studies was evaluated and the relevant data items were extracted, summarized and
      analyzed. A total of 21 studies were discussed in this review representing 12
      different interventions. While several trials had positive findings, the major
      methodological limitations of the studies meant that no definitive evidence could
      be found supporting any of the interventions. Future trials are needed which
      address the methodological problems identified in this review. Exercise holds
      promise for future research based on its proven benefit in breast cancer.

PMID- 29380530
TI  - "How I approach..."-A new series in Pediatric Blood & Cancer.

PMID- 29380529
TI  - Physical frailty after liver transplantation.
AB  - Frailty is prevalent in liver transplant candidates, but little is known of what
      happens to frailty after liver transplantation. We analyzed data for 214 adult
      liver transplant recipients who had >=1 frailty assessment using the Liver
      Frailty Index (LFI) at 3- (n = 178), 6- (n = 139), or 12- (n = 107) months
      posttransplant (higher values=more frail). "Frail" and "robust" were defined as
      LFI >=4.5 and <3.2. Median pre-liver transplant LFI was 3.7, and was worse at 3
      months (3.9; P = .02), similar at 6 months (3.7; P = .07), and improved at 12
      months (3.4; P < .001). The percentage who were robust pre- and 3-, 6-, and 12
      months posttransplant were 25%, 14%, 28%, and 37%; the percentage frail were 21%,
      21%, 10%, and 7%. In univariable analysis, each 0.1 pretransplant LFI point more
      frail was associated with a decreased odds of being robust at 3- (odds ratio [OR]
      0.75), 6- (OR 0.77), and 12-months (OR 0.90) posttransplant (P <= .001), which
      did not change substantially with multivariable adjustment. In conclusion,
      frailty worsens 3 months posttransplant and improves modestly by 12 months, but
      fewer than 2 of 5 patients achieve robustness. Pretransplant LFI was a potent
      predictor of posttransplant robustness. Aggressive interventions aimed at
      preventing frailty pretransplant are urgently needed to maximize physical health
      after liver transplantation.

PMID- 29380531
TI  - Does cochlear implant brand influence patient satisfaction? A survey of 102
      cochlear implant users.

PMID- 29380532
TI  - Energy Transfer in Dye-Coupled Lanthanide-Doped Nanoparticles: From Design to
      Application.
AB  - Surface modification with organic dye molecules is a useful strategy to
      manipulate the optical properties of lanthanide-doped nanoparticles (LnNPs). It
      enables energy transfer between dyes and LnNPs, which provides unprecedented
      possibilities to gain new optical phenomena from the dye-LnNPs composite systems.
      This has led to a wide range of emerging applications, such as biosensing, drug
      delivery, gene targeting, information storage, and photon energy conversion.
      Herein, the mechanism of energy transfer and the structural-dependent energy
      transfer properties in dye-coupled LnNPs are reviewed. The design strategies for
      achieving effective dye-LnNP functionalization are presented. Recent advances in
      these composite nanomaterials in biomedicine and energy conversion applications
      are highlighted.

PMID- 29380533
TI  - Analysis of anti-melanoma differentiation-associated gene 5 antibody in Hong Kong
      Chinese patients with idiopathic inflammatory myopathies: diagnostic utility and
      clinical correlations.
AB  - AIM: To compare the prevalence of the anti-melanoma differentiation-associated
      gene 5 antibody (anti-MDA5 Ab) in Hong Kong Chinese patients with dermatomyositis
      (DM) and polymyositis (PM); in addition, to examine the association of anti-MDA5
      Ab and the clinical characteristics of these patients. METHODS: Twenty
      consecutive existing patients with DM being followed up at the Rheumatology
      Clinic of Kwong Wah Hospital, Hong Kong were recruited. Twenty patients with PM
      were recruited from the same clinic as the controls. A commercial line blot
      immunoassay was used to detect the anti-MDA5 Ab in all the participants. The
      frequencies of anti-MDA-5 Ab in the two groups were compared. The clinical
      characteristics of the patients with and without the antibody were analyzed.
      RESULTS: Anti-MDA5 Ab was found in 30% of patients with DM but not in patients
      with PM. All patients with the antibody exhibited the clinically amyopathic DM
      (CADM) phenotype. These patients were predominantly male, younger and with
      shorter disease duration. Anti-MDA5 Ab was significantly associated with rapidly
      progressive interstitial lung disease (RP-ILD) and digital ulcers. No
      statistically significant association was found between other disease or
      treatment variables and the antibody. CONCLUSION: Anti-MDA5 Ab is found
      exclusively in DM patients of the CADM subtype and is associated with RP-ILD and
      digital ulcers, suggesting that examination of this antibody is clinically useful
      in Hong Kong Chinese patients with idiopathic inflammatory myopathies. However,
      further studies are required to assess its prognostic significance, and to
      explore the difference of its presentations in various populations.

PMID- 29380534
TI  - Serum-based six-miRNA signature as a potential marker for EC diagnosis:
      Comparison with TCGA miRNAseq dataset and identification of miRNA-mRNA target
      pairs by integrated analysis of TCGA miRNAseq and RNAseq datasets.
AB  - AIM: To evaluate the diagnostic potential of a six microRNAs (miRNAs) panel
      consisting of miR-21, miR-144, miR-107, miR-342, miR-93 and miR-152 for
      esophageal cancer (EC) detection. METHODS: The expression of miRNAs was analyzed
      in EC sera samples using quantitative real-time PCR. Risk score analysis was
      performed and linear regression models were then fitted to generate the six-miRNA
      panel. In addition, we made an effort to identify significantly dysregulated
      miRNAs and mRNAs in EC using the Cancer Genome Atlas (TCGA) miRNAseq and RNAseq
      datasets, respectively. Further, we identified significantly correlated miRNA
      mRNA target pairs by integrating TCGA EC miRNAseq dataset with RNAseq dataset.
      RESULTS: The panel of circulating miRNAs showed enhanced sensitivity (87.5%) and
      specificity (90.48%) in terms of discriminating EC patients from normal subjects
      (area under the curve [AUC] = 0.968). Pathway enrichment analysis for potential
      targets of six miRNAs revealed 48 significant (P < 0.05) pathways, viz. pathways
      in cancer, mRNA surveillance, MAPK, Wnt, mTOR signaling, and so on. The
      expression data for mRNAs and miRNAs, downloaded from TCGA database, lead to
      identification of 2309 differentially expressed genes and 189 miRNAs. Gene
      ontology and pathway enrichment analysis showed that cell-cycle processes were
      most significantly enriched for differentially expressed mRNA. Integrated
      analysis of TCGA miRNAseq and RNAseq datasets resulted in identification of 53
      063 significantly and negatively correlated miRNA-mRNA pairs. CONCLUSION: In
      summary, a novel and highly sensitive signature of serum miRNAs was identified
      for EC detection. Moreover, this is the first report identifying miRNA-mRNA
      target pairs from EC TCGA dataset, thus providing a comprehensive resource for
      understanding the interactions existing between miRNA and their target mRNAs in
      EC.

PMID- 29380535
TI  - Parent perspectives on information about late effects of childhood cancer
      treatment and their role in initial treatment decision making.
AB  - BACKGROUND: Though most childhood cancer survivors experience late effects of
      treatment, we know little about parent preferences for late effects information
      during therapy, or how parents weigh late effects when making treatment
      decisions. Our objective was to explore how parents of children with cancer
      consider late effects in initial treatment decision making and during active
      cancer treatment. METHODS: Semistructured interviews were conducted with 12
      parents of children with cancer who were actively receiving treatment at Dana
      Farber/Boston Children's Cancer and Blood Disorders Center. Interviews were audio
      recorded, transcribed verbatim, and qualitatively analyzed using thematic
      analysis. RESULTS: Ten of 12 parents reported that they had to decide between two
      or more treatment options for their child's cancer. Of those, 50% (5/10)
      considered late effects to be an important factor in their decision making. Most
      parents wanted early and detailed information about their child's risk of late
      effects to make treatment decisions and to feel prepared for the future. However,
      a few parents felt too overwhelmed to focus on late effects at diagnosis. While
      many recalled extensive late effects information in informed consent discussions,
      some parents felt these issues were minimally addressed. CONCLUSION: Parents
      desire detailed information about late effects to make informed treatment
      decisions and prepare for the future. Despite the role of late effects in
      treatment decision making, some parents feel that late effects are either
      inadequately addressed or too overwhelming to process at diagnosis. Parents may
      benefit from early assessment of their information needs and a return to these
      issues over time.

PMID- 29380536
TI  - Cellulose synthase 'class specific regions' are intrinsically disordered and
      functionally undifferentiated.
AB  - Cellulose synthases (CESAs) are glycosyltransferases that catalyze formation of
      cellulose microfibrils in plant cell walls. Seed plant CESA isoforms cluster in
      six phylogenetic clades, whose non-interchangeable members play distinct roles
      within cellulose synthesis complexes (CSCs). A 'class specific region' (CSR),
      with higher sequence similarity within versus between functional CESA classes,
      has been suggested to contribute to specific activities or interactions of
      different isoforms. We investigated CESA isoform specificity in the moss,
      Physcomitrella patens (Hedw.) B. S. G. to gain evolutionary insights into CESA
      structure/function relationships. Like seed plants, P. patens has oligomeric
      rosette-type CSCs, but the PpCESAs diverged independently and form a separate
      CESA clade. We showed that P. patens has two functionally distinct CESAs classes,
      based on the ability to complement the gametophore-negative phenotype of a
      ppcesa5 knockout line. Thus, non-interchangeable CESA classes evolved separately
      in mosses and seed plants. However, testing of chimeric moss CESA genes for
      complementation demonstrated that functional class-specificity is not determined
      by the CSR. Sequence analysis and computational modeling showed that the CSR is
      intrinsically disordered and contains predicted molecular recognition features,
      consistent with a possible role in CESA oligomerization and explaining the
      evolution of class-specific sequences without selection for class-specific
      function.

PMID- 29380537
TI  - Identification of a small-molecule ligand of beta-arrestin1 as an inhibitor of
      stromal fibroblast cell migration accelerated by cancer cells.
AB  - Stromal fibroblasts, which occupy a major portion of the tumor microenvironment,
      play an important role in cancer metastasis. Thus, targeting of these fibroblasts
      activated by cancer cells (carcinoma-associated fibroblasts; CAFs) might aid in
      the improved treatment of cancer metastasis. NIH3T3 fibroblasts cocultured with
      MCF7 cells displayed enhanced migration compared to NIH3T3 fibroblasts cultured
      alone. We used this system to identify the small-molecule inhibitors responsible
      for their enhanced migration, a characteristic of CAFs. We selected beta
      arrestin1, which showed high expression in cocultured cells, as a molecular
      target for such inhibitors. Cofilin, a protein downstream of beta-arrestin1, is
      activated/dephosphorylated in this condition. The small-molecule ligands of beta
      arrestin1 obtained by chemical array were then examined using a wound healing
      coculture assay. RKN5755 was identified as a selective inhibitor of activated
      fibroblasts. RKN5755 inhibited the enhanced migration of fibroblasts cocultured
      with cancer cells by binding to beta-arrestin1 and interfering with beta
      arrestin1-mediated cofilin signaling pathways. Therefore, these results
      demonstrate the role of beta-arrestin1 in the activation of fibroblasts and
      inhibiting this protein by small molecule inhibitor might be a potential
      therapeutic target for the stromal fibroblast activation (cancer-stroma
      interaction).

PMID- 29380538
TI  - Determining the prevalence of vestibular screening failures in pediatric cancer
      patients whose therapies include radiation to the head/neck and platin-based
      therapies: A pilot study.
AB  - BACKGROUND: Sensorineural hearing loss due to ototoxic cancer therapy is well
      established; effects on the vestibular system are unknown. We examined the
      feasibility of implementing vestibular screens for pediatric cancer survivors
      exposed to ototoxic agents. The prevalence of screening failures is reported.
      METHODS: Cancer survivors who were 6-17 years, at least 1-month posttreatment,
      and received ototoxic therapy (radiation to the head/neck, cisplatin,
      carboplatin) were eligible. Screening measures included (1) Pediatric Vestibular
      Symptom Questionnaire, (2) Modified Clinical Test of Sensory Interaction on
      Balance, and (3) Dynamic Visual Acuity. RESULTS: Vestibular screening failures
      were observed in 30 participants (60%). Patients with a brain tumor diagnosis
      were at increased risk for failures compared to nonbrain tumor patients (74.2%
      vs. 36.8%, P = 0.009). Patients who underwent brain surgery were at increased
      risk for failures compared to patients without brain surgery (71% vs. 42%, P =
      0.043). Patients with a longer duration between end of treatment and vestibular
      screening had a reduced risk of failures, with an almost 20% decrease for each
      year between the time points (odds ratio = 0.812; 95% confidence interval: 0.683
      0.964, P = 0.018). Receiving carboplatin correlated with a decreased risk of
      failure (P = 0.016), due to a negative correlation with other clinical risk
      factors (diagnosis of a brain tumor, major brain surgery) that are associated
      with vestibular screening failure. CONCLUSION: Vestibular screening failures are
      highly prevalent in childhood cancer survivors who received ototoxic therapy.
      Broad screening of this population and further characterization of these patients
      are warranted.

PMID- 29380539
TI  - Cross talk between beta subunits, intracellular Ca2+ signaling, and SNAREs in the
      modulation of CaV 2.1 channel steady-state inactivation.
AB  - Modulation of CaV 2.1 channel activity plays a key role in interneuronal
      communication and synaptic plasticity. SNAREs interact with a specific synprint
      site at the second intracellular loop (LII-III) of the CaV 2.1 pore-forming
      alpha1A subunit to optimize neurotransmitter release from presynaptic terminals
      by allowing secretory vesicles docking near the Ca2+ entry pathway, and by
      modulating the voltage dependence of channel steady-state inactivation. Ca2+
      influx through CaV 2.1 also promotes channel inactivation. This process seems to
      involve Ca2+ -calmodulin interaction with two adjacent sites in the alpha1A
      carboxyl tail (C-tail) (the IQ-like motif and the Calmodulin-Binding Domain (CBD)
      site), and contributes to long-term potentiation and spatial learning and memory.
      Besides, binding of regulatory beta subunits to the alpha interaction domain
      (AID) at the first intracellular loop (LI-II) of alpha1A determines the degree of
      channel inactivation by both voltage and Ca2+ . Here, we explore the cross talk
      between beta subunits, Ca2+ , and syntaxin-1A-modulated CaV 2.1 inactivation,
      highlighting the alpha1A domains involved in such process. beta3 -containing CaV
      2.1 channels show syntaxin-1A-modulated but no Ca2+ -dependent steady-state
      inactivation. Conversely, beta2a -containing CaV 2.1 channels show Ca2+ 
      dependent but not syntaxin-1A-modulated steady-state inactivation. A LI-II
      deletion confers Ca2+ -dependent inactivation and prevents modulation by syntaxin
      1A in beta3 -containing CaV 2.1 channels. Mutation of the IQ-like motif, unlike
      CBD deletion, abolishes Ca2+ -dependent inactivation and confers modulation by
      syntaxin-1A in beta2a -containing CaV 2.1 channels. Altogether, these results
      suggest that LI-II structural modifications determine the regulation of CaV 2.1
      steady-state inactivation either by Ca2+ or by SNAREs but not by both.

PMID- 29380540
TI  - X-Shaped alpha-FeOOH with Enhanced Charge Separation for Visible-Light-Driven
      Photocatalytic Overall Water Splitting.
AB  - Photocatalytic overall water splitting (POWS) is a promising route for converting
      solar energy into green and sustainable energy. Herein, we report a facile
      hydrothermal approach for the fabrication of x-shaped alpha-FeOOH photocatalysts
      containing high-index facets for POWS. The x-shaped alpha-FeOOH photocatalysts
      exhibited enhanced visible-light-driven POWS activities in comparison with that
      of FeOOH without x-structures, with a maximum H2 and O2 evolution rate of 9.2 and
      4.7 MUmol h-1  g-1 , respectively. The morphology and particle size of the alpha
      FeOOH could be controlled by adjusting the NH4 F concentration in the precursors.
      The photodeposition of Pt and RuO2 on the x-shaped alpha-FeOOH revealed the
      specially separated reduction and oxidation centers on the surface of alpha
      FeOOH, with the oxidation-active sites selectively located on the edges of the
      alpha-FeOOH x-structures. Electrochemical experiments further affirmed the
      enhanced charge separation in the x-shaped alpha-FeOOH. The smaller particle size
      and unique x-shape of the alpha-FeOOH photocatalyst were shown to enhance the
      POWS performance owing to the large specific surface area, high proportion of
      exposed high-index facets, high electron-transfer efficiency and effective
      separation of the photogenerated electron-hole pairs. The current study revealed
      that the x-shaped alpha-FeOOH products could serve as cost-effective and stable
      photocatalysts for POWS.

PMID- 29380541
TI  - Molecular Design of Phenanthrenequinone Derivatives as Organic Cathode Materials.
AB  - Conjugated carbonyl compounds have become the most promising type of organic
      electrode materials for rechargeable Li-ion batteries because only they can
      achieve simultaneously high energy density, high cycling stability, and high
      power density. In this work, we have performed first-principles density
      functional theory (DFT) calculations to explore the fundamental rules of how the
      electronic structure and redox properties of a typical conjugated carbonyl
      compound, phenanthrenequinone (PQ), are modified by adjusting the heteroaromatic
      building blocks. Such a molecular design strategy allows for the improvement in
      discharge potential while the specific capacity remains nearly unchanged. The
      correlation between the electronic structures and redox properties for the
      designed PQ derivatives is systematically discussed. It is demonstrated that the
      discharge potential of the PQ derivatives depends strongly on the frontier
      orbital levels, the electric potential, and the Li-bonding configurations. The
      electrostatic potential (ESP) maps show visible displays of molecular electric
      structures and can be applied to understand how the redox properties of the PQ
      derivatives are modified by the heteroaromatic building blocks.

PMID- 29380542
TI  - Effectiveness and acceptability of continuous glucose monitoring for type 2
      diabetes management: A narrative review.
AB  - The present narrative review discusses the role of continuous glucose monitoring
      (CGM) in glycemic and weight control, and lifestyle behavior adherence in adults
      with type 2 diabetes. A literature search from January 2001 to November 2017 was
      carried out (MEDLINE, CINAHL, Web of Science and Scopus). Eligible studies were
      trials evaluating the use of CGM with the aim of achieving glucose control or
      lifestyle-related treatment adherence over a period of >=8 weeks in adults with
      type 2 diabetes compared with usual care or another comparison intervention, or
      observational trials reporting CGM user experience. A total of 5,542 participants
      were recruited into 11 studies (eight randomized controlled trials [n = 5,346]
      and three observational studies [n = 196]). The sample size ranged 6-4,678
      participants, the mean age was 51.7-60.0 years and diabetes duration was 2.1-19.2
      years, with high heterogeneity between studies. Overall, the available evidence
      showed, compared with traditional self-monitoring of blood glucose levels, CGM
      promoted greater reductions in glycated hemoglobin, bodyweight and caloric
      intake; higher adherence rating to a personal eating plan; and increases in
      physical activity. High compliance to CGM wear-time and device calibration was
      reported (>90%). The addition of lifestyle and/or behavioral counseling to CGM
      appeared to further potentiate these improvements. Preliminary evidence suggests
      that CGM use promotes glycemic and weight control, and lifestyle behavior
      adherence in adults with type 2 diabetes. These benefits might be further
      enhanced with integration of diet, exercise, and glucose excursion education and
      counseling. However, specific attributes of effective interventions and the
      application of CGM information for promoting improved outcomes and healthier
      choices remain unclear.

PMID- 29380543
TI  - Mechanochemical Decomposition of Crystalline Cellulose in the Presence of
      Protonated Layered Niobium Molybdate Solid Acid Catalyst.
AB  - Direct depolymerization of crystalline cellulose into water-soluble sugars by
      solvent-free ball milling was examined in the presence of a strongly acidic
      layered metal oxide, HNbMoO6 , resulting in full conversion with 72 % yield of
      water-soluble sugars. Measurements by 13 C cross-polarization magic angle
      spinning NMR spectroscopy and X-ray diffraction revealed that amorphization of
      cellulose occurred rapidly within 10 min. Scanning electron microscopy equipped
      with an energy dispersive X-ray indicated that the substrate and the catalyst
      were well mixed during milling. The time course of the product distribution
      showed that most of the resultant water-soluble sugars were produced not by
      successive degradation of oligosaccharides but by direct depolymerization of
      cellulose chains. The products included glucose, mannose, and cello-oligomers, as
      well as anhydrosugars. Addition of small amounts of polar solvents increased the
      sugar yield, whereas further addition of water decreased the selectivity to
      anhydrosugars. Calculations of the mechanical energy required for the ball
      milling process showed that 0.02 % was utilized for the chemical transformation
      under the conditions examined in this study.

PMID- 29380545
TI  - Diffusion Kurtosis Imaging Shows Similar Cerebral Axonal Damage in Patients with
      HIV Infection and Multiple Sclerosis.
AB  - BACKGROUND AND PURPOSE: In this pilot study, we sought to investigate the
      pathological changes in the white matter (WM) of medically complex, combination
      antiretroviral therapy (cART)-treated patients with human immunodeficiency virus
      (HIV), comparing them to patients with long-standing, secondary progressive
      multiple sclerosis (SPMS). METHODS: Using diffusion kurtosis imaging (DKI)
      derived WM tract integrity (WMTI) metrics, 15 HIV and 15 age- and sex-matched
      SPMS patients with similar disease duration underwent magnetic resonance imaging
      analysis. Maps of WMTI metrics were created. Tract-based spatial statistics
      analysis of the whole brain and regions of interest analysis of the corpus
      callosum (CC) and the anterior thalamic radiations (ATRs) were performed and the
      derived WMTI metrics were compared between the groups of patients. RESULTS:
      Axonal water fraction, an index of chronic axonal loss, showed similarities
      between HIV and the chronic MS patients in all regions; in contrast, tortuosity,
      a measure more sensitive to myelin loss, was regionally variable. In addition, in
      HIV patients, WMTI metrics of the CC and left ATR were associated with cognitive
      test scores, suggesting clinical relevance for these measures of WM damage.
      CONCLUSIONS: We conclude that DKI-derived WMTI metrics may be a valuable tool in
      assessing the WM changes of medically complex HIV-infected individuals. While not
      powered to examine potential etiologies of WM changes in this pilot sample,
      regional variations in WMTI metrics were seen. When contrasted with changes
      consequent to chronic MS of similar duration, HIV and its comorbidities appear to
      result in similar degrees of axonal damage, but regionally variable amounts of
      myelin loss and extraxonal abnormality.

PMID- 29380546
TI  - Icosahedral Pt-Ni Nanocrystalline Electrocatalyst: Growth Mechanism and Oxygen
      Reduction Activity.
AB  - Engineering the structure of Pt alloy offers an effective way to the design of
      high performance electrocatalysts. Herein, we synthesize a sandwich-structured,
      icosahedral Pt2.1 Ni catalyst through a hot injection method. Its growth involves
      three steps: 1) burst nucleation of Pt atoms to form a Pt-enriched core, 2)
      heterogeneous nucleation of Ni atoms onto the Pt core to form a Ni-enriched
      interlayer, and 3) kinetic controlled growth of a Pt-enriched shell. The Pt
      enriched core protects the nanostructure from collapse and mitigates the strain
      change caused by lattice mismatch, and thus enhances the stability of the
      structure. The Ni-enriched interlayer induces the electronic modification of the
      outermost Pt shell, and in turn tunes the activity. The Pt-enriched shell
      provides more active sites through the exposure of (1 1 1) facets and retards the
      dissolution of Ni atoms. As a result, this sandwich-structure enables impressive
      electrocatalytic activity (0.91 mA cm-2 and 0.32 AmgPt-1 @ 0.9 V) and duability.

PMID- 29380544
TI  - Folate action in nervous system development and disease.
AB  - The vitamin folic acid has been recognized as a crucial environmental factor for
      nervous system development. From the early fetal stages of the formation of the
      presumptive spinal cord and brain to the maturation and maintenance of the
      nervous system during infancy and childhood, folate levels and its
      supplementation have been considered influential in the clinical outcome of
      infants and children affected by neurological diseases. Despite the vast
      epidemiological information recorded on folate function and neural tube defects,
      neural development and neurodegenerative diseases, the mechanisms of folate
      action in the developing neural tissue have remained elusive. Here we compiled
      studies that argue for a unique role for folate in nervous system development and
      function and its consequences to neural disease and repair. (c) 2018 Wiley
      Periodicals, Inc. Develop Neurobiol 78: 391-402, 2018.

PMID- 29380547
TI  - Assessment of the American Joint Commission on Cancer 8th Edition Staging System
      for Patients with Pancreatic Neuroendocrine Tumors: A Surveillance, Epidemiology,
      and End Results analysis.
AB  - Although several staging systems have been proposed for pancreatic neuroendocrine
      tumors (pNETs), the optimal staging system remains unclear. Here, we aimed to
      assess the application of the newly revised 8th edition American Joint Committee
      on Cancer (AJCC) staging system for exocrine pancreatic carcinoma (EPC) to pNETs,
      in comparison with that of other staging systems. We identified pNETs patients
      from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2014).
      Overall survival was analyzed using Kaplan-Meier curves with the log-rank test.
      The predictive accuracy of each staging system was assessed by the concordance
      index (c-index). Cox proportional hazards regression was conducted to calculate
      the impact of different stages. In total, 2424 patients with pNETs, including
      2350 who underwent resection, were identified using SEER data. Patients with
      different stages were evenly stratified based on the 8th edition AJCC staging
      system for EPC. Kaplan-Meier curves were well separated in all patients and
      patients with resection using the 8th edition AJCC staging system for EPC.
      Moreover, the hazard ratio increased with worsening disease stage. The c-index of
      the 8th edition AJCC staging system for EPC was similar to that of the other
      systems. For pNETs patients, the 8th edition AJCC staging system for EPC exhibits
      good prognostic discrimination among different stages in both all patients and
      those with resection.

PMID- 29380548
TI  - Corneal confocal microscopy detects severe small fiber neuropathy in diabetic
      patients with Charcot neuroarthropathy.
AB  - AIMS/INTRODUCTION: The aim of the present study was to identify the extent of
      small fiber neuropathy in diabetic patients with Charcot neuroarthropathy (CN).
      MATERIALS AND METHODS: A total of 20 patients with CN were compared with 20 age-
      and diabetes duration-matched patients with type 2 diabetes and 20 age-matched
      control participants. All patients underwent corneal confocal microscopy with
      quantification of corneal nerve morphology and assessment for vibration
      perception threshold, and a subset of patients with CN underwent assessment of
      sudomotor function and neuropathic pain. RESULTS: In patients with CN compared
      with type 2 diabetes patients and control participants, there was a significant
      reduction in corneal nerve fiber density (14.94 +/- 8.23 vs 23.86 +/- 7.71, P =
      0.004 vs 34.84 +/- 9.13, P < 0.001), corneal nerve branch density (18.61 +/- 16.7
      vs 41.62 +/- 22.67, P = 0.032 vs 76.47 +/- 38.44, P < 0.001) and corneal nerve
      fiber length (8.40 +/- 4.83 vs 14.87 +/- 4.76, P = 0.001 vs 21.24 +/- 6.48, P <
      0.001), electrochemical skin conductance on the feet (20.57 +/- 13.99 vs 61.50 +/
      22.26, P < 0.001 vs 76.23 +/- 12.01, P < 0.001) and hands (30.86 +/- 18.10 vs
      61.13 +/- 19.14, P = 0.001 vs 68.31 +/- 11.96, P < 0.001), and a significant
      increase in the vibration perception threshold in the feet (38.46 +/- 15.10 vs
      14.15 +/- 10.25, P < 0.001 vs 7.75 +/- 4.01, P < 0.001). CONCLUSIONS: Patients
      with diabetes and CN have severe large and particularly small fiber neuropathy.

PMID- 29380549
TI  - Enantioselective N-Heterocyclic Carbene Catalysis via the Dienyl Acyl Azolium.
AB  - Herein we report the enantioselective N-heterocyclic carbene catalyzed (4+2)
      annulation of the dienyl acyl azolium with enolates. The reaction exploits
      readily accessible acyl fluorides and TMS enol ethers to give a range of highly
      enantio- and diastereo-enriched cyclohexenes (most >97:3 er and >20:1 dr). The
      reaction was found to require high nucleophilicity NHC catalysts with mechanistic
      studies supporting a stepwise 1,6-addition/beta-lactonization.

PMID- 29380550
TI  - Distinct predictive impact of FISH abnormality in proteasome inhibitors and
      immunomodulatory agents response: redefining high-risk multiple myeloma in Asian
      patients.
AB  - For risk-adaptive therapeutic approaches in multiple myeloma (MM) treatment, we
      analyzed treatment outcome according to in situ hybridization (FISH) profiles to
      investigate the prognostic and predictive values of structural variations in a
      large series of Asian population. A total of 565 newly diagnosed patients with
      multiple myeloma between January 2005 and June 2015 were evaluated. FISH results
      showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in
      2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520),
      and +1q21 in 40.8% (211/517). The presence of del(17p13), IgH rearrangement, and
      t(14;16) was associated with worse overall survival. Interestingly, however, the
      presence of t(4;14) conferred little prognostic impact. Treatment-specific
      analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and
      trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the
      other hand, patients with del(13q14) and del(9p21) were less likely to benefit
      from lenalidomide. Autologous stem cell transplantation (autoSCT) was less
      effective in patients with del(17p13), t(14;16), and trisomy 1q21. Predictive
      values of del(17p13) and t(14;16) to bortezomib and autoSCT are seemingly
      universal, but predictive marker del(13q14) and del(9p21) for lenalidomide
      response appears ethnicity-specific. Thus, FISH profiles in MM treatment should
      be interpreted with regards to patient's ethnicity.

PMID- 29380551
TI  - Targeted deletion of RIC8A in mouse neural precursor cells interferes with the
      development of the brain, eyes, and muscles.
AB  - Autosomal recessive disorders such as Fukuyama congenital muscular dystrophy,
      Walker-Warburg syndrome, and the muscle-eye-brain disease are characterized by
      defects in the development of patient's brain, eyes, and skeletal muscles. These
      syndromes are accompanied by brain malformations like type II lissencephaly in
      the cerebral cortex with characteristic overmigrations of neurons through the
      breaches of the pial basement membrane. The signaling pathways activated by
      laminin receptors, dystroglycan and integrins, control the integrity of the
      basement membrane, and their malfunctioning may underlie the pathologies found in
      the rise of defects reminiscent of these syndromes. Similar defects in
      corticogenesis and neuromuscular disorders were found in mice when RIC8A was
      specifically removed from neural precursor cells. RIC8A regulates a subset of G
      protein alpha subunits and in several model organisms, it has been reported to
      participate in the control of cell division, signaling, and migration. Here, we
      studied the role of RIC8A in the development of the brain, muscles, and eyes of
      the neural precursor-specific conditional Ric8a knockout mice. The absence of
      RIC8A severely affected the attachment and positioning of radial glial processes,
      Cajal-Retzius' cells, and the arachnoid trabeculae, and these mice displayed
      additional defects in the lens, skeletal muscles, and heart development. All the
      discovered defects might be linked to aberrancies in cell adhesion and migration,
      suggesting that RIC8A has a crucial role in the regulation of cell-extracellular
      matrix interactions and that its removal leads to the phenotype characteristic to
      type II lissencephaly-associated diseases. (c) 2018 Wiley Periodicals, Inc.
      Develop Neurobiol 78: 374-390, 2018.

PMID- 29380552
TI  - Outbreak of Salmonella Typhimurium associated with feeder rodents.
AB  - In December 2012, an increase in human Salmonella Typhimurium cases was
      identified in the province of Ontario, Canada launching an outbreak
      investigation. The outbreak spanned 3 years (2012-2014), with 134 cases reported
      from five Canadian provinces. There was a substantial burden of illness among
      children: 45% of cases were children 12 years old or under, and 23% of cases were
      under 5 years old. Epidemiologic, traceback and laboratory findings linked this
      outbreak to feeder rodents (used to feed snakes) supplied by a network of rodent
      breeders in Ontario. Cases likely acquired their illness through either direct or
      indirect contact with feeder rodents. This investigation not only contributes to
      the weight of evidence on the risk that feeder rodents pose, but also underscores
      the importance of investigating indirect animal contact and associated risks,
      especially for high-risk individuals.

PMID- 29380553
TI  - Development and validation of risk models to predict the 7-year risk of type 2
      diabetes: The Japan Epidemiology Collaboration on Occupational Health Study.
AB  - AIMS/INTRODUCTION: We previously developed a 3-year diabetes risk score in the
      working population. The objective of the present study was to develop and
      validate flexible risk models that can predict the risk of diabetes for any
      arbitrary time-point during 7 years. MATERIALS AND METHODS: The participants were
      46,198 Japanese employees aged 30-59 years, without diabetes at baseline and with
      a maximum follow-up period of 8 years. Incident diabetes was defined according to
      the American Diabetes Association criteria. With routine health checkup data
      (age, sex, abdominal obesity, body mass index, smoking status, hypertension
      status, dyslipidemia, glycated hemoglobin and fasting plasma glucose), we
      developed non-invasive and invasive risk models based on the Cox proportional
      hazards regression model among a random two-thirds of the participants, and used
      another one-third for validation. RESULTS: The range of the area under the
      receiver operating characteristic curve increased from 0.73 (95% confidence
      interval 0.72-0.74) for the non-invasive prediction model to 0.89 (95% confidence
      interval 0.89-0.90) for the invasive prediction model containing dyslipidemia,
      glycated hemoglobin and fasting plasma glucose. The invasive models showed
      improved integrated discrimination and reclassification performance, as compared
      with the non-invasive model. Calibration appeared good between the predicted and
      observed risks. These models performed well in the validation cohort.
      CONCLUSIONS: The present non-invasive and invasive models for the prediction of
      diabetes risk up to 7 years showed fair and excellent performance, respectively.
      The invasive models can be used to identify high-risk individuals, who would
      benefit greatly from lifestyle modification for the prevention or delay of
      diabetes.

PMID- 29380554
TI  - Did parents have it right all along? Parents, risk, and living kidney donation:
      Revisiting the arguments for and against parental living donation of kidneys.
AB  - Historically, living kidney donation has been justified in part by our belief
      that living donors face minimal risks of subsequent disease. Recent research has
      brought that presumption into question, particularly for younger donors including
      parents. In light of this finding, we re-examine many of the traditional
      arguments both for and against the practice of parental living kidney donation.
      We then propose an alternative framework in which the burden of having a child
      with end-stage kidney disease can be considered as an illness experienced by the
      potential donor parent. We believe this allows a more straightforward, as well as
      more accurate, assessment of the risks and benefits of donation for the potential
      parental donor. This assessment might then be used to best inform the decision
      whether or not to proceed with kidney donation using a shared decision-making
      model, while reflecting the appropriate ethical roles of both the potential donor
      and the transplantation program.

PMID- 29380555
TI  - The double-edged sword of endoplasmic reticulum stress in uremic sarcopenia
      through myogenesis perturbation.
AB  - BACKGROUND: Sarcopenia is the age-related degeneration characterized with the
      decline of skeletal muscle mass, strength, and function. The imbalance of protein
      synthesis and degradation which jeopardizes immune, hormone regulation, and
      muscle-motor neuron connection is the main cause of sarcopenia. There is limited
      knowledge regarding molecular mechanism of sarcopenia. As the endoplasmic
      reticulum is the control centre of the protein syntheses and degradation, we
      hypothesized that endoplasmic reticulum stress and unfolded protein response
      (UPR) play an important in the development of sarcopenia. Understanding the
      sarcopenia molecular mechanisms may benefit the therapeutic diagnosis and
      treatment in the future. METHODS: Mouse myoblast C2C12 cells are exposed to
      designated time and concentration of indoxyl sulfate (IS), a uremic toxin of
      chronic kidney disease. The proliferation, differentiation, and the expression of
      atrogin 1 are examined. The protein and mRNA expression of IS treated-C2C12 cells
      are inspected to distinguish the role of ER stress and oxidative stress
      underlying the sarcopenia. RESULTS: Indoxyl sulfate inhibits myoblast
      differentiation. We demonstrate that as the number of multi-nuclei myotube
      decreased, the differentiation markers including myoD, myoG, and myosin heavy
      chain are also suppressed. Indoxyl sulfate inhibits myoblast proliferation and
      induces the myotubular atrophy marker atrogin-1 protein expression. Indoxyl
      sulfate stimulates eIF2alpha phosphorylation and XBP1 mRNA splicing in UPR.
      Interestingly, the oxidative stress is related to eIF2alpha phosphorylation but
      not XBP1 mRNA splicing. The eIF2alpha phosphorylation triggered by IS reduces
      myoD, myoG, and myosin heavy chain protein expression, which represents the anti
      myogenic modulation on the early differentiation event. The XBP1 mRNA splicing
      induced by IS, however, is considered the adaptive response to restore the
      myogenic differentiation. CONCLUSIONS: Our studies indicated that the ER stress
      and UPR modulation are critical in the chronic kidney disease uremic toxin
      accumulated sarcopenia model. We believe that UPR-related signals showed great
      potential in clinical application.

PMID- 29380556
TI  - Pediatric ABO-incompatible kidney transplantation: Evolving with the advancing
      apheresis technology: A single-center experience.
AB  - Recent literature has endorsed favorable outcomes following ABOi kidney
      transplantation in pediatric population. Nevertheless, reluctance to pursue an
      ABOi still remains pervasive. This could be ascribed to various legitimate
      reasons, namely less extensive pediatric ABOi data, technical difficulties
      encountered during PP, cost restraints, and concerns regarding higher rates of
      antibody-mediated rejection, infectious complications, and post-transplant
      lymphoproliferative disorder as compared to adults. However, given the similar
      excellent outcomes of both ABOi and ABOc kidney transplantation, clinicians
      should consider this option sooner if a compatible donor or swap is not
      available. Here, we describe the outcomes of three pediatric ABOi performed at
      our institute in India (from 2014 till now), wherein distinct apheresis
      modalities had been employed in each desensitization protocol, and our techniques
      evolved with advancing science in apheresis. This case series includes India's
      first published pediatric ABO-incompatible transplant (Case 2) and the youngest
      child to undergo ABO-incompatible renal transplant in SAARC nations (Case 3).

PMID- 29380557
TI  - hmSOD1 gene mutation-induced disturbance in iron metabolism is mediated by
      impairment of Akt signalling pathway.
AB  - BACKGROUND: Recently, skeletal muscle atrophy, impairment of iron metabolism, and
      insulin signalling have been reported in rats suffering from amyotrophic lateral
      sclerosis (ALS). However, the interrelationship between these changes has not
      been studied. We hypothesize that an impaired Akt-FOXO3a signalling pathway
      triggers changes in the iron metabolism in the muscles of transgenic animals.
      METHODS: In the present study, we used transgenic rats bearing the G93A hmSOD1
      gene and their non-transgenic littermates. The study was performed on the muscles
      taken from animals at three different stages of the disease: asymptomatic (ALS
      I), the onset of the disease (ALS II), and the terminal stage of the disease (ALS
      III). In order to study the molecular mechanism of changes in iron metabolism, we
      used SH-SY5Y and C2C12 cell lines stably transfected with pcDNA3.1, SOD1 WT and
      SOD1 G93A, or FOXO3a TM-ER. RESULTS: A significant decrease in P-Akt level and
      changes in iron metabolism were observed even in the group of ALS I animals. This
      was accompanied by an increase in the active form of FOXO3a, up-regulation of
      atrogin-1, and catalase. However, significant muscle atrophy was observed in ALS
      II animals. An increase in ferritin L and H was accompanied by a rise in PCBP1
      and APP protein levels. In SH-SY5Y cells stably expressing SOD1 or SOD1 G93A, we
      observed elevated levels of ferritin L and H and non-haem iron. Interestingly,
      insulin treatment significantly down-regulated ferritin L and H proteins in the
      cell. Conversely, cells transfected with small interfering RNA against Akt 1, 2,
      3, respectively, showed a significant increase in the ferritin and FOXO3a levels.
      In order to assess the role of FOXO3a in the ferritin expression, we constructed
      a line of SH-SY5Y cells that expressed a fusion protein made of FOXO3a fused at
      the C-terminus with the ligand-binding domain of the oestrogen receptor (TM-ER)
      being activated by 4-hydroxytamoxifen. Treatment of the cells with 4
      hydroxytamoxifen significantly up-regulated ferritin L and H proteins level.
      CONCLUSIONS: Our data suggest that impairment of insulin signalling and iron
      metabolism in the skeletal muscle precedes muscle atrophy and is mediated by
      changes in Akt/FOXO3a signalling pathways.

PMID- 29380559
TI  - Fixed-dose combination of sofosbuvir and ledipasvir in the treatment of hepatitis
      C infection in patients on hemodialysis: Report of an initial experience.

PMID- 29380558
TI  - Evaluation of the UVB-screening capacity and restorative effects exerted by
      farnesol gel on UVB-caused sunburn.
AB  - Farnesol, a natural 15-carbon organic compound, has various microbiological and
      cellular activities. It has been found to exert apoptosis-inducing effects
      against carcinoma cells as well as antiallergic and anti-inflammatory effects in
      vivo. In the current study, a series of formulations composed of various
      concentrations of hydroxypropyl methylcellulose (HPMC) with the addition of
      hyaluronan (HA) and xanthan gum (XG) was designed to evaluate the UVB-screening
      and H2 O2 -eliminating effects of farnesol in normal fibroblasts. Farnesol at
      0.005, 0.0075, and 0.01% exhibited significant capacity for H2 O2 scavenging; at
      0.0025%, it showed insignificant effects. Under 120-min UVB exposure, screening
      with plural gel composed of 0.0025% farnesol, 0.5% HA, and 0.5% XG containing
      1.5% or 2% HPMC retained normal fibroblast viability. After 60-min exposure to
      UVB, screening with plural gel composed of farnesol, HA, XG, and 0.5%, 1.0%,
      1.5%, or 2% HPMC decreased the ratio of the G1 phase and increased ratio of the S
      phase in comparison with the accumulated cell cycle of the normal fibroblasts
      without screening. The gel with 2% HPMC displayed the strongest cell cycle
      reversal ability. In vivo histopathological results showed that the prepared
      plural gels with 0.5% or 2% HPMC and farnesol, HA, and XG had greater
      antiphotoaging and reparative effects against UVB-induced changes and damage in
      the skin. In conclusion, the current in vitro and in vivo results demonstrated
      that the prepared plural composed of 0.0025% farnesol, 0.5% HA, 0.5% XG, and 2%
      HPMC possessed the greatest UVB-screening capacity and the strongest restorative
      effects on UVB-induced sunburned skin.

PMID- 29380560
TI  - Solution-Processable Balanced Ambipolar Field-Effect Transistors Based on
      Carbonyl-Regulated Copolymers.
AB  - It is very important to develop ambipolar field effect transistors to construct
      complementary circuits. To obtain balanced hole- and electron-transport
      properties, one of the key issues is to regulate the energy levels of the
      frontier orbitals of the semiconductor materials by structural tailoring, so that
      they match well with the electrode Fermi levels. Five conjugated copolymers were
      synthesized and exhibited low LUMO energy levels and narrow bandgaps on account
      of the strong electron-withdrawing effect of the carbonyl groups. Polymer thin
      film transistors were prepared by using a solution method and exhibited high and
      balanced hole and electron mobility of up to 0.46 cm2  V-1  s-1 , which suggested
      that these copolymers are promising ambipolar semiconductor materials.

PMID- 29380561
TI  - Doxycycline attenuates chronic intermittent hypoxia-induced atrial fibrosis in
      rats.
AB  - INTRODUCTION: Atrial structural remodeling in the form of fibrosis contributes to
      the arrhythmic substrate in atrial fibrillation (AF). The aim of this study was
      to investigate the effects of doxycycline on chronic intermittent hypoxia (CIH)
      induced atrial fibrosis and the pathophysiological mechanisms underlying such
      changes. METHODS: A total of 30 Sprague Dawley rats were randomized into three
      groups: control group, CIH group, and CIH with doxycycline treatment (CIH-D)
      group. CIH lasted 5 hours per day for 4 weeks. CIH-D rats were administrated
      doxycycline for 4 weeks, while they received CIH. Masson's trichrome staining was
      used to determine collagen deposit in the atrial myocardium. Protein and mRNA
      levels of Matrix Metalloproteinase-2 (MMP-2) and -9 (MMP-9), microRNA-21 (miR-21)
      and its downstream target Sprouty1 (Spry1), and extracellular signal-regulated
      kinases 1/2 (ERK1/2) were measured using Western blotting or real-time qRT-PCR,
      respectively. RESULTS: Compared to the control group, the CIH group showed higher
      interstitial collagen fraction, increased MMP-9, miR-21, and p-ERK1/2 levels, and
      decreased MMP-2 and Spry1 levels. Doxycycline treatment attenuated CIH-induced
      atrial fibrosis, reduced MMP-2, MMP-9, miR-21, and p-ERK1/2, and increased Spry1.
      CONCLUSIONS: CIH treatment induced significant atrial fibrosis in our rat model,
      which was attenuated by doxycycline. These changes can be explained by
      alterations in the MMP and miR-21/ERK signaling pathways.

PMID- 29380562
TI  - The differences on efficacy of oxaliplatin in locally advanced colon cancer
      between mucinous and nonmucinous adenocarcinoma.
AB  - Until now, it remains unclear how to best use the histological subtype in
      clinical practice. This study aimed to compare differences in the efficacy of
      postoperative chemotherapy among different histological subtypes of colon
      adenocarcinomas. Using the Surveillance, Epidemiology, and End Results-Medicare
      database, 51,200 patients with stage II or III primary colon carcinomas who
      underwent resection for curative intent between 1992 and 2008 were included. The
      survival benefit was evaluated using a Cox proportional hazards model,
      interaction analyses, and propensity score-matched techniques. There was no
      significant difference in survival for low-risk stage II mucinous adenocarcinoma
      (MA) or nonmucinous adenocarcinoma (NMA) between 5-FU and oxaliplatin-treated
      groups (P = 0.387 for MA, P = 0.629 for NMA). Patients with high-risk stage II
      NMA who received the oxaliplatin chemotherapy regimen had significantly improved
      cancer-specific survival (CSS) compared with the 5-FU group (P = 0.004), while
      those with MA saw no improvement (P = 0.690). For stage III tumors, patients with
      NMA who received the oxaliplatin chemotherapy regimen had significantly improved
      CSS compared with the 5-FU group (P < 0.001), while those with MA saw no
      improvement (P = 0.300). There were significant interactions between chemotherapy
      regimen and histological subtype. For patients with resected colon cancer who
      received 5-FU-based postoperative chemotherapy, oxaliplatin chemotherapy prolongs
      CSS for stage III and high-risk stage II NMA. Conversely, there was no similar
      improvement with addition of oxaliplatin for patients with stage III or stage II
      MA.

PMID- 29380563
TI  - CD34+ Cell Transplantation Improves Right Ventricular Function in Patients with
      Nonischemic Dilated Cardiomyopathy.
AB  - We investigated the effects of CD34+ cell therapy on right ventricular (RV)
      function in patients with nonischemic dilated cardiomyopathy (DCM). We enrolled
      60 patients with DCM who were randomized to CD34+ cell therapy (Stem Cells (SC)
      Group n = 30), or no cell therapy (Controls, n = 30). The SC Group received
      granulocyte-colony stimulating factor, and CD34+ cells were collected by
      apheresis and injected transendocardially. Patients were followed for 6 months.
      At baseline, the groups did not differ in age, gender, left ventricular ejection
      fraction, N-terminal probrain natriuretic peptide, or parameters of RV function.
      At 6 months, we found a significant improvement in RV function in the SC Group
      (tricuspid annular plane systolic excursion [TAPSE]: +0.44 +/- 0.64 cm, p = .001;
      peak systolic tissue Doppler velocity of tricuspid annulus [St]: +1.5 +/- 2.1
      cm/s; p = .001; percent of fractional area change [FAC]: +8.6% +/- 5%, p = .01),
      but not in Controls (TAPSE: -0.07 +/- 0.32 cm, p = .40; St: -0.1 +/- 1.2 cm/s; p
      = .44; FAC: -1.2% +/- 3.2%, p = .50). On repeat electroanatomical mapping, we
      found an improvement in interventricular septum viability in 19 of 30 patients
      from the SC Group; this correlated with the improvements in RV function (13/19 in
      the improved septum group versus 3/11 in the remaining cohort, p = .029). These
      results suggest that patients with DCM, changes in RV function correlate with
      changes of viability of interventricular septum. CD34+ cell therapy appears to be
      associated with improved right ventricular function in this patient cohort.
      (Clinical Trial Registration Information: www.clinicaltrials.gov; NCT02248532).
      Stem Cells Translational Medicine 2018;7:168-172.

PMID- 29380565
TI  - Deep-tissue temperature mapping by multi-illumination photoacoustic tomography
      aided by a diffusion optical model: a numerical study.
AB  - Temperature mapping during thermotherapy can help precisely control the heating
      process, both temporally and spatially, to efficiently kill the tumor cells and
      prevent the healthy tissues from heating damage. Photoacoustic tomography (PAT)
      has been used for noninvasive temperature mapping with high sensitivity, based on
      the linear correlation between the tissue's Gruneisen parameter and temperature.
      However, limited by the tissue's unknown optical properties and thus the optical
      fluence at depths beyond the optical diffusion limit, the reported PAT
      thermometry usually takes a ratiometric measurement at different temperatures and
      thus cannot provide absolute measurements. Moreover, ratiometric measurement over
      time at different temperatures has to assume that the tissue's optical properties
      do not change with temperatures, which is usually not valid due to the
      temperature-induced hemodynamic changes. We propose an optical-diffusion-model
      enhanced PAT temperature mapping that can obtain the absolute temperature
      distribution in deep tissue, without the need of multiple measurements at
      different temperatures. Based on the initial acoustic pressure reconstructed from
      multi-illumination photoacoustic signals, both the local optical fluence and the
      optical parameters including absorption and scattering coefficients are first
      estimated by the optical-diffusion model, then the temperature distribution is
      obtained from the reconstructed Gruneisen parameters. We have developed a
      mathematic model for the multi-illumination PAT of absolute temperatures, and our
      two-dimensional numerical simulations have shown the feasibility of this new
      method. The proposed absolute temperature mapping method may set the technical
      foundation for better temperature control in deep tissue in thermotherapy.

PMID- 29380564
TI  - In Situ Tissue Regeneration of Renal Tissue Induced by Collagen Hydrogel
      Injection.
AB  - Host stem/progenitor cells can be mobilized and recruited to a target location
      using biomaterials, and these cells may be used for in situ tissue regeneration.
      The objective of this study was to investigate whether host biologic resources
      could be used to regenerate renal tissue in situ. Collagen hydrogel was injected
      into the kidneys of normal mice, and rat kidneys that had sustained
      ischemia/reperfusion injury. After injection, the kidneys of both animal models
      were examined up to 4 weeks for host tissue response. The infiltrating host cells
      present within the injection regions expressed renal stem/progenitor cell
      markers, PAX-2, CD24, and CD133, as well as mesenchymal stem cell marker, CD44.
      The regenerated renal structures were identified by immunohistochemistry for
      renal cell specific markers, including synaptopodin and CD31 for glomeruli and
      cytokeratin and neprilysin for tubules. Quantitatively, the number of glomeruli
      found in the injected regions was significantly higher when compared to normal
      regions of renal cortex. This phenomenon occurred in normal and ischemic injured
      kidneys. Furthermore, the renal function after ischemia/reperfusion injury was
      recovered after collagen hydrogel injection. These results demonstrate that
      introduction of biomaterials into the kidney is able to facilitate the
      regeneration of glomerular and tubular structures in normal and injured kidneys.
      Such an approach has the potential to become a simple and effective treatment for
      patients with renal failure. Stem Cells Translational Medicine 2018;7:241-250.

PMID- 29380566
TI  - [Recent advances in directed evolution].
AB  - Screening is the bottleneck of directed evolution. In order to address this
      problem, a series of novel semi-rational designed strategies have been developed
      based on combinatorial active-site saturation test and iterative saturation
      mutagenesis, including single code saturation mutagenesis, double code saturation
      mutagenesis and triple code saturation mutagenesis. By creation of "small and
      smart" high qualified mutant libraries and combinatorial mutagenesis of specific
      sites, these new strategies have been successfully applied in multiparameter
      optimization, e.g. stereo/regioselectivity and activity. This review summarized
      recent advances in directed evolution and its applications in biocatalysis field.

PMID- 29380567
TI  - [Metabolic engineering of (E)-beta-farnesene synthase genes for aphid-resistant
      genetically modified plants].
AB  - Aphids are major agricultural pests that cause significant yield losses of crops
      each year. (E)-beta-farnesene (EbetaF), as the main component of the aphid alarm
      pheromones, can interrupt aphid feeding and cause other conspecies in the
      vicinity to become agitated or disperse from their host plant. Furthermore,
      EbetaF can function as a kairomone in attracting aphid predators. EbetaF synthase
      genes, which encode enzymes that convert farnesyl diphosphate (FPP) to the
      acyclic sesquiterpene EbetaF, have been isolated and characterized from
      peppermint (Mentha * piperita and Mentha asiatica), Yuzu (Citrus junos), Douglas
      fir (Pseudotsuga menziesii), sweet wormwood (Artemisia annua) and chamomile
      (Matricaria recutita), respectively. Transgenic plant overexpressing EbetaF
      synthase genes has been one of the most efficient strategies for aphid
      management. In this review, the current statuses of transgenic plants engineered
      for aphid resistance were summarized. The plant-derived EbetaF synthase genes
      with their potential roles in aphid management via genetic-modified (GM)
      approaches were reviewed. The existing problem in GM plants with EbetaF synthase
      gene, such as low EbetaF emission was usually detected in the transgenic plant,
      was discussed and the development direction in this area was proposed.

PMID- 29380568
TI  - [Advances in metabolic engineering for the microbial production of naturally
      occurring terpenes-limonene and bisabolene: a mini review].
AB  - Limonene (C10H16) and bisabolene (C15H24) are both naturally occurring terpenes
      in plants. Depending on the number of C5 units, limonene and bisabolene are
      recognized as representative monoterpenes and sesquiterpenes, respectively.
      Limonene and bisabolene are important pharmaceutical and nutraceutical products
      used in the prevention and treatment of cancer and many other diseases. In
      addition, they can be used as starting materials to produce a range of
      commercially valuable products, such as pharmaceuticals, nutraceuticals,
      cosmetics, and biofuels. The low abundance or yield of limonene and bisabolene in
      plants renders their isolation from plant sources non-economically viable.
      Isolation of limonene and bisabolene from plants also suffers from low efficiency
      and often requires harsh reaction conditions, prolonged reaction times, and
      expensive equipment cost. Recently, the rapid developments in metabolic
      engineering of microbes provide a promising alternative route for producing these
      plant natural products. Therefore, producing limonene and bisabolene by
      engineering microbial cells into microbial factories is becoming an attractive
      alternative approach that can overcome the bottlenecks, making it more
      sustainable, environmentally friendly and economically competitive. Here, we
      reviewed the status of metabolic engineering of microbes that produce limonene
      and bisabolene including microbial hosts, key enzymes, metabolic pathways and
      engineering of limonene/bisabolene biosynthesis. Furthermore, key challenges and
      future perspectives were discussed.

PMID- 29380569
TI  - [Status and advances of long-acting factor VIII].
AB  - Current treatment for hemophilia A is based on replacement therapy that is the
      most effective method by using recombinant clotting factor FVIII (rFVIII).
      Although the safety and effectiveness of replacement therapy has been proved by
      clinical practice for the last decades, FVIII products are temporally limited
      because of a short half-life and requiring prophylactic injections frequently for
      most patients, usually three times per week or every other day. Frequent
      intravenous injection not only brings physical pain to the patient, but also
      produces FVIII antibodies that seriously affect the treatment effect. In this
      paper, we review the present status, research progress and main problems of the
      long-acting recombinant factor VIII.

PMID- 29380570
TI  - [Development of an ELISA for identification of immunodominant protein antigens of
      Mycoplasma hyopneumoniae].
AB  - We developed a method to identify serological humoral immunodominant proteinic
      antigen of Mycoplasma hyopneumoniae (Mhp). After constructing the recombinant
      plasmid pGEX-6P-1-mhp366 and transforming it into Escherichia coli BL21(DE3), the
      recombinant GST-Mhp366 protein was expressed successfully. The lysates of the
      recombinant GST-Mhp366 and genetic engineering GST were added into glutathione
      coated plates and reacted with 17 positive sera or 13 negative sera. Meanwhile,
      the optimization of experimental conditions, including coated antigen, blocking
      buffer, dilutions of sera and second antibody were determined. The optimal
      concentration of the coated antigen was the original bacteria lysates without
      dilution, and the optimal blocking buffer contained 10% FBS and 2.5% skim milk in
      PBS. Besides, the working concentration of serum samples and the HRP-tagged
      rabbit anti-pig IgG secondary antibody were 1:500 and 1:40 000, respectively.
      Thus, an indirect ELISA was established for identification of immunodominant
      protein antigens of Mhp. Meanwhile, this method was confirmed by the identified
      serological humoral immunodominant proteinic antigen Mhp156 and Mhp364. This
      method can be used for identification of the candidate vaccine antigens on a
      genome-wide scale. Furthermore, it can lay the foundation for identifying the
      candidate vaccine antigens through colostra and the nasal mucosal secretions.

PMID- 29380571
TI  - [Effect of MIG1 and SNF1 deletion on simultaneous utilization of glucose and
      xylose by Saccharomyces cerevisiae].
AB  - Mig1 and Snf1 are two key regulatory factors involved in glucose repression of
      Saccharomyces cerevisiae. To enhance simultaneous utilization of glucose and
      xylose by engineered S. cerevisiae, single and double deletion strains of MIG1
      and SNF1 were constructed. Combining shake flask fermentations and transcriptome
      analysis by RNA-Seq, the mechanism of Mig1 and Snf1 hierarchically regulating
      differentially expressed genes that might affect simultaneous utilization of
      glucose and xylose were elucidated. MIG1 deletion did not show any significant
      effect on co-utilization of mixed sugars. SNF1 deletion facilitated xylose
      consumption in mixed sugars as well as co-utilization of glucose and xylose,
      which might be due to that the SNF1 deletion resulted in the de-repression of
      some genes under nitrogen catabolite repression, thereby favorable to the
      utilization of nitrogen nutrient. Further deletion of MIG1 gene in the SNF1
      deletion strain resulted in the de-repression of more genes under nitrogen
      catabolite repression and up-regulation of genes involved in carbon central
      metabolism. Compared with wild type strain, the MIG1 and SNF1 double deletion
      strain could co-utilize glucose and xylose, and accelerate ethanol accumulation,
      although this strain consumed glucose faster and xylose slower. Taken together,
      the MIG1 and SNF1 deletions resulted in up-regulation of genes under nitrogen
      catabolite repression, which could be beneficial to simultaneous utilization of
      glucose and xylose. Mig1 and Snf1 might be involved in the hierarchical
      regulatory network of genes under nitrogen catabolite repression. Dissection of
      this regulatory network could provide further insights to new targets for
      improving co-utilization of glucose and xylose.

PMID- 29380572
TI  - [A highly active GH11 xylanase from Penicillium sp. L1 with potential
      applications in xylo-oligosaccharide production].
AB  - Xylanase is a high-profile glycoside hydrolase with applications in brewing,
      feed, pharmacy and bioenergy industries, but most of xylanases are in active
      below 30 C. In order to obtain low temperature active xylanase, a xylanase gene,
      XYN11A, was cloned from Penicillium sp. L1 and expressed in Pichia pastoris
      GS115. After purification and enzyme assay, optimal pH and temperature were
      determined to be 3.5 to 4.0 and 55 C. This enzyme was stable at acid and neutral
      condition (pH 1.0 to 7.0) or under the treatment of 40 C for 1 hour. This
      xylanase displayed strong resistance to all tested ions and chemicals.
      Noteworthily, XYN11A maintained a higher activity of 6 700 U/mg than a lot of
      GH11 xylanase, and demonstrated higher activity (24% to 58%) at lower temperature
      from 20 to 40 C. After beechwood xylan hydrolysis for 16 h, the hydrolysates
      consisted mainly of xylobiose, xylotriose and xylotetraose and barely of xylose,
      thus XYN11A could be used for the production of prebiotic xylooligosaccharide.
      Possessing the features of acidophilic, highly active at lower temperature and
      oligosaccharide production, XYN11A demonstrated great potential in food and feed
      industrials.

PMID- 29380573
TI  - [Expression and characterization of juvenile hormone binding protein Bmtol gene
      in silkworm, Bombyx mori].
AB  - The head of the silkworm is a nerve center and a sense organ, contains antennaes
      and sensory hair, feels the outside signal, and responds to the external signal
      delivered to the brain. Juvenile hormone is mainly synthesized and secreted by
      corpora allata, and it needs to be played with the aid of the hormone binding
      protein, because the juvenile hormone binding protein is the carrier of juvenile
      hormone transport and plays a functional in vivo, they have an extremely
      important function in insects. The objective of this study is to screened and
      identify a novel BmTOL proteins that it has a conserved structure of the juvenile
      hormone binding protein family by SilkDB and NCBI database. Its coding gene
      number is BGIBMGA003404 (GenBank Accession No. KY681053). We also expressed the
      recombinant protein using the prokaryotic expression system, and then
      successfully purified the recombinant protein by Ni-NTA chromatography column to
      generate the polyclonal antibodies. The expression patterns analysis in various
      tissues showed that both in transcriptional and protein levels Bmtol was higher
      expressed in head. Furthermore, the expression level of Bmtol gene was higher in
      newly exuviated silkworm, and expression level of Bmtol gene was lower from at 3
      days 5th instar to 7 days pupa, began to increase after the moth.
      Immunohistochemistry showed that BmTOL protein was localized in the cortex,
      antennaes and brain of the head, It may be related to the information
      transmission of the head, and provides an important source of information for the
      growth and development of silkworm.

PMID- 29380574
TI  - [Effect of extracellular cyclophilin A on inflammatory response and anti
      inflammatory activity of antibody against cyclophilin A].
AB  - Cyclophilin A (CypA) is a member of peptidyl prolylisomerases (PPIase) family.
      CypA is best known as a ubiquitously distributed intracellular protein. It has
      also been shown to be secreted by cells in response to inflammatory stimuli and
      oxidative stress. Extracellular CypA (eCypA) interacts with CD147 to initiate
      inflammatory responses via recruiting leucocytes into inflamed tissue.
      Recombinant CypA was expressed in Escherichia coli and then purified using
      Superdex 75TM 16/60. The results of Real-time PCR and ELISA showed that the
      expression levels of proinflammatory cytokines, such as IL-1beta, secreted by
      eCypA stimulated BMDM were significantly up-regulated, indicating that eCypA
      played an important role in promoting inflammatory responses. In addition, anti
      CypA antibody was prepared using purified CypA protein for therapeutic evaluation
      in a mouse model of LPS-induced acute lung inflammation. Antibody-treated mice
      showed reduced lung injury and the expression levels of IL-1beta in the lung
      tissue and blood were decreased significantly, indicating that anti-CypA antibody
      exerted a potent anti-inflammatory activity. Our findings provide a potential
      therapeutic antibody for inflammation-mediated diseases.

PMID- 29380575
TI  - [Preparation and identification of polyclonal antibodies against Moraxella
      catarrhalis UspA1].
AB  - To prepare polyclonal antibodies (PcAb) against UspA1 of Moraxella catarrhalis
      (Mc), we used bioinformatic analysis to determine the surface exposed region in
      this protein that holds the antigen epitopes. Then the corresponding coding
      sequences for this fragment was artificially synthesized according to the codon
      usage of Escherichia coli. The gene fragment was then subcloned into the
      prokaryotic expression vector pET-28a(+) and expressed in E. coli rosseta (DE3),
      and then the recombinant UspA1-His proteins were purified. Two New Zealand white
      rabbits were immunized with this protein to prepare antiserum. The resulting PcAb
      was then purified from the antiserum with Protein A affinity column. The results
      of fluorescence antibody assay, enzyme linked immunosorbent assay and Western
      blotting analysis showed that the PcAb could specifically recognize the surface
      exposed region of UspA1 on Mc. The preparation of the PcAb laid a foundation of
      further development of rapid detection technique for M. catarrhalis.

PMID- 29380576
TI  - [Construction of CD36 gene silencing cell lines by lentivirus-mediated RNA
      interference and the effect on protein expression of caveolin-1].
AB  - CD36, the major scavenger receptor, is intimately involved in the uptake of oxLDL
      in macrophages. To further study the function of CD36 in macrophages, we
      constructed CD36 gene silence cell lines (J774A.1) by lentivirus-mediated RNA
      interference technique, and analyzed the effect of CD36 in caveolin-1 protein
      expression. At first, 5 shRNA fragments were designed and synthesized according
      to the coding sequence (CDS) region of CD36 gene. Next, the CD36-shRNA was
      inserted into lentiviral vector to yield pLKO.1-CD36-shRNA plasmid. After DNA
      sequencing, the pLKO.1-CD36-shRNA plasmid and psiCHECK-II-CD36 were co
      transfected into the 293T cells to screen the efficient CD36-shRNA. The efficient
      CD36-shRNA plasmid and the helper plasmid were co-transfected into the 293T cells
      to package the lentivirus, and then infected the J774A.1 cells. After screening
      by puromycin, CD36 gene silence cell lines (J774A.1) was established. Western
      blotting and confocal fluorescence microscopy results showed that the CD36
      silencing efficiency in the gene silence cell line was 90%. Accompanied by a
      decrease in CD36 protein on cell surface, oxLDL binding to CD36 was significantly
      inhibited, indicating that the CD36 gene silence cell line is successfully
      established. Finally, the oxLDL stimulation and inhibitor experiments results
      showed that the CD36 knockdown significantly suppresses the phosphorylation of
      JNK and ERK, thereby inhibiting the oxLDL-induced caveolin-1 protein expression,
      demonstrating that CD36 modulates the caveolin-1 protein expression through the
      JNK/ERK-mediated signaling transduction.

PMID- 29380577
TI  - [Annotation of the mobilomes of nine teleost species].
AB  - In this study, the mobilomes of nine teleost species were annotated by
      bioinformatics methods. Both of the mobilome size and constitute displayed a
      significant difference in 9 species of teleost fishes. The species of mobilome
      content ranking from high to low were zebrafish, medaka, tilapia, coelacanth,
      platyfish, cod, stickleback, tetradon and fugu. Mobilome content and genome size
      were positively correlated. The DNA transposons displayed higher diversity and
      larger variation in teleost (0.50% to 38.37%), was a major determinant of
      differences in teleost mobilomes, and hAT and Tc/Mariner superfamily were the
      major DNA transposons in teleost. RNA transposons also exhibited high diversity
      in teleost, LINE transposons accounted for 0.53% to 5.75% teleost genomic
      sequences, and 14 superfamilies were detected. L1, L2, RTE and Rex
      retrotransposons obtained significant amplification. While LTR displayed low
      amplification in most teleost with less than 2% of genome coverages, except in
      zebrafish and stickleback, where LTR reachs 5.58% and 2.51% of genome coverages
      respectively. And 6 LTR superfamilies (Copia, DIRS, ERV, Gypsy, Ngaro and Pao)
      were detected in the teleost, and Gypsy exhibits obvious amplication among them.
      While the SINE represents the weakest ampification types in teleost, only within
      zebrafish and coelacanth, it represents 3.28% and 5.64% of genome coverages, in
      the other 7 teleost, it occupies less than 1% of genomes, and tRNA, 5S and MIR
      families of SINE have a certain degree of amplification in some teleosts. This
      study shows that the teleost display high diversity and large variation of
      mobilome, there is a strong correlation with the size variations of genomes and
      mobilome contents in teleost, mobilome is an important factor in determining the
      teleost genome size.

PMID- 29380578
TI  - [Tandem expression and activity determination of antibacterial peptide Spinosan-C
      from Paa spinosa].
AB  - Antibacterial peptide can be easily degraded by protease and has the lethal
      effect on the host Escherichia coli. In order to solve these problems and further
      improve the expression ability of the Escherichia coli system, the antimicrobial
      peptide Spinosan-C of Paa spinosa was studied. First, the codon of Spinosan-C was
      optimized according to E. coli codon usage frequency. Then, the 8 multimeric
      Spinosan-C gene (8*Spinosan-C) was synthesized and cloned into prokaryotic
      expression vector pET-28a. The fusion antimicrobial peptide 8*Spinosan-C was
      further highly expressed in Escherichia coli strain Rosetta. The recombinant
      8*Spinosan-C protein was then purified and cleaved specially by formic acid to
      generate the Spinosan-C monomer. Antibacterial test in vitro suggested that the
      cleaved Spinosan-C monomer had antibacterial bioactivity against the test
      bacteria. This study provides a technical reference for the largescale
      preparation of frog antimicrobial peptides.

PMID- 29380579
TI  - [Synthesis of vitamin K2 by isopentenyl transferase NovA in Pichia pastoris
      Gpn12].
AB  - The effect of methanol addition on the heterologous expression of isoprenyl
      transferase NovQ was studied in Pichia pastoris Gpn12, with menadione and
      isopentenol as precursors to catalyze vitamin K2 (MK-3) synthesis. The expression
      of NovQ increased by 36% when 2% methanol was added every 24 h. The influence of
      initial pH, temperature, methanol addition, precursors (menadione, isopentenol)
      addition, catalytic time and cetyltrimethyl-ammonium bromide (CTAB) addition were
      explored in the P. pastoris whole-cell catalytic synthesis process of MK-3 in
      shaking flask. Three significant factors were then studied by response surface
      method. The optimal catalytic conditions obtained were as follows: catalytic
      temperature 31.56 C, menadione 295.54 mg/L, catalytic time 15.87 h. Consistent
      with the response surface prediction results, the optimized yield of MK-3 reached
      98.47 mg/L in shaking flask, 35% higher than that of the control group. On this
      basis, the production in a 30-L fermenter reached 189.67 mg/L when the cell
      catalyst of 220 g/L (dry weight) was used to catalyze the synthesis for 24 h.
      This method laid the foundation for the large-scale production of MK-3 by P.
      pastoris Gpn12.

PMID- 29380580
TI  - Extraglottic airway devices: is the classification in generations really
      informative of properties and safety?

PMID- 29380581
TI  - Heuristic to systematic approach to difficult airways prediction. Is it time to
      change habits?

PMID- 29380583
TI  - The uncertainty of prognostication following intracerebral hemorrhage.

PMID- 29380582
TI  - Novel anticoagulants and liver transplantation: is thromboelastography the key?

PMID- 29380584
TI  - The safe use of I-gel for tracheostomy in neurodegenerative diseases.

PMID- 29380585
TI  - Positive end-expiratory pressure and recruitment maneuvers in obese patients:
      should we chase oxygenation?

PMID- 29380586
TI  - We still lack an effective method to identify the best supraglottic airway
      device.

PMID- 29380587
TI  - Dose matters: optimized dosing is part of optimized care.

PMID- 29380588
TI  - Neuraxial anesthesia and septic meningitis: please be reminded.

PMID- 29380589
TI  - SCIENTISTS and SCIENCE ADVOCATES: Dr. Younes Karimi (1929-2008), the Prominent
      Iranian Physician in the Field of Plague and Other Infectious Diseases

PMID- 29380590
TI  - Dilute Au-Containing Ag Nanosponges as a Highly Active and Durable
      Electrocatalyst for Oxygen Reduction and Alcohol Oxidation Reactions.
AB  - Zero-dimensional nanoparticles (NPs) have been demonstrated as the promising
      class of catalysts for various chemical and electrochemical reactions. However,
      the emerging Au-Ag NP catalysts suffer from single functionality, limited
      activity enhancement, and unsatisfactory stability problems. Here, we report a
      facile kinetically controlled solution method to prepare a new class of Au-Ag
      nanoporous sponges (NSs) composed of three-dimensional networks without using
      additional stabilizing agents at room temperature. The unexpected shift of the d
      band center in our Au-Ag NSs was observed for the first time in Au-Ag bimetallic
      systems, which effectively activates the Au-Ag NSs for electrochemical reactions.
      The robust electronic effect coupled with abundant accessible active sites from
      the hierarchically porous architecture make the bare Au-Ag NSs a superior
      multifunctional catalyst for oxygen reduction, ethylene glycol (EG) oxidation,
      and glucose oxidation reactions compared to the commercial Pt/C electrocatalyst
      in alkaline medium. The optimized AuAg3.2 NSs deliver a mass activity of 1.26 A
      mgAu-1 toward oxygen reduction reaction, which is ~8.2 times as high as that of
      the Pt/C electrocatalyst, simultaneously showing outstanding stability with
      negligible activity decay after 10 000 cycles. For the anodic reactions, these
      AuAg3.2 NSs show extremely high activity and stability toward both EG and glucose
      catalytic oxidation reactions with a higher mass activity of 7.58 and 1.48 A mgAu
      1, about 3- and 18.5-fold enhancement than Pt/C, respectively. This work provides
      important insights into the structural design, performance optimization, and cost
      reduction to promote the practical applications of liquid fuel cells.

PMID- 29380591
TI  - Inkjet-Printed Multiwavelength Thermoplasmonic Images for Anticounterfeiting
      Applications.
AB  - Inkjet printing of thermoplasmonic nanoparticles enables instantaneous, large
      area heat pattern generation upon light illumination from distance. By printing
      multiple metal nanoparticles of different shapes overlaid, we can fabricate
      multiwavelength thermoplasmonic images, which generate different heat patterns
      from a single printed image depending on the wavelength choice of light. In this
      work, we propose a novel multiwavelength thermoplasmonic image printing process
      that can be used for anticounterfeit technology. With this technology, "printed
      thermoplasmonic labels" allow fully secured anticounterfeit inspection procedure.
      Input stimulus of near-infrared or infrared light illumination and output signal
      reading of thermal patterns can be both completely invisible. Wavelength
      selective photothermal effect also enables the encryption of the contained
      information, which adds more complexity and thus higher security.

PMID- 29380592
TI  - Neonicotinoid Residues in Fruits and Vegetables: An Integrated Dietary Exposure
      Assessment Approach.
AB  - Neonicotinoids have become the most widely used insecticides in the world since
      introduced in the mid 1990s, yet the extent of human exposure and health impacts
      is not fully understood. In this study, the residues were analyzed of seven
      neonicotinoids in fruit and vegetable samples collected from two cross-sectional
      studies: the U.S. Congressional Cafeteria study (USCC) and the Hangzhou China
      (HZC) study. We then employed a relative potency factor method to integrate all
      neonicotinoids in each food sample using the respective reference dose values as
      the basis for summation. The findings were compared with data published by the
      U.S. Department of Agriculture Pesticide Data Program (USDA/PDP). Imidacloprid
      and thiamethoxam were the most commonly detected neonicotinoids in fruits and
      vegetables with 66 and 51% detection in the HZC study and 52 and 53% detection in
      the USCC study, respectively. The overall frequency of detection for
      neonicotinoids in the USDA/PDP samples was much lower than those reported here
      for the USCC or HZC studies, with imidacloprid being the most frequently detected
      neonicotinoid at 7.3%. The high frequencies of neonicotinoid detection in fruits
      and vegetables in the USCC and HZC studies give us a snapshot of the ubiquity of
      neonicotinoid use in global agriculture and make it clear that neonicotinoids
      have become part of the dietary staple, with possible health implications for
      individuals.

PMID- 29380593
TI  - Efficient and Reproducible CH3NH3PbI3 Perovskite Layer Prepared Using a Binary
      Solvent Containing a Cyclic Urea Additive.
AB  - An efficient CH3NH3PbI3 perovskite solar cell whose performance is reproducible
      and shows reduced dependence on the processing conditions is fabricated using the
      cyclic urea compound 1,3-dimethyl-2-imidazolidinone (DMI) as an additive to the
      precursor solution of CH3NH3PbI3. X-ray diffraction analysis reveals that DMI
      weakly coordinates with PbI2 and forms a CH3NH3PbI3 film (film-DMI) with no
      intermediate phase. The surface of annealed film-DMI (film-DMI-A) was smooth,
      with an average crystal size of 1 MUm. Photoluminescence and transient
      photovoltage measurements show that film-DMI-A exhibits a longer carrier lifetime
      than a CH3NH3PbI3 film prepared using the strongly coordinating additive dimethyl
      sulfoxide (DMSO) (film-DMSO-A) because of the reduced number of defect sites in
      film-DMI-A. A solar cell based on film-DMI-A exhibits a higher power conversion
      efficiency (17.6%) than that of a cell based on film-DMSO-A (15.8%). Furthermore,
      the performance of the film-DMI-A solar cell is less sensitive to the ratio
      between PbI2 and DMI, and film-DMI can be fabricated under a high relative
      humidity of 55%.

PMID- 29380594
TI  - High-Efficiency and High-Color-Rendering-Index Semitransparent Polymer Solar
      Cells Induced by Photonic Crystals and Surface Plasmon Resonance.
AB  - Semitransparent polymer solar cells (ST-PSCs) show attractive potential in power
      generating windows or building-integrated photovoltaics. However, the development
      of ST-PSCs is lagging behind opaque PSCs because of the contradiction between
      device efficiency and transmission. Herein, Ag/Au alloy nanoparticles and
      photonic crystals (PCs) were simultaneously introduced into ST-PSCs, acting
      compatibly as localized surface plasmon resonances and distributed Bragg
      reflectors to enhance light absorption and transmission. As a result, ST-PSCs
      based on a hybrid PTB7-Th:PC71BM active layer contribute an efficiency as high as
      7.13 +/- 0.15% and an average visible transmission beyond 20%, which are superior
      to most of the reported results. Furthermore, PCs can partly compensate valley
      range of transmission by balancing reflection and transmission regions, yielding
      a high color rendering index of 95. We believe that the idea of two light
      management methods compatibly enhancing the performance of ST-PSCs can offer a
      promising path to develop photovoltaic applications.

PMID- 29380595
TI  - Spectrometer-Free Plasmonic Biosensing with Metal-Insulator-Metal Nanocup Arrays.
AB  - The development of high performing and accessible sensors is crucial to future
      point-of-care diagnostic sensing systems. Here, we report on a gold-titanium
      dioxide-gold metal-insulator-metal plasmonic nanocup array device for
      spectrometer-free refractometric sensing with a performance exceeding
      conventional surface plasmon resonance sensors. This device shows distinct
      spectral properties such that a superstrate refractive index increase causes a
      transmission intensity increase at the peak resonance wavelength. There is no
      spectral shift at this peak and there are spectral regions with no transmission
      intensity change, which can be used as internal device references. The sensing
      mechanism, plasmon-cavity coupling optimization, and material properties are
      studied using electromagnetic simulations. The optimal device structure is
      determined using simulation and experimental parameter sweeps to tune the cavity
      confinement and the resonance coupling. An experimental sensitivity of 800
      DeltaT%/RIU is demonstrated. Spectrometer-free, imaged-based detection is also
      carried out for the cancer biomarker carcinoembryonic antigen with a 10 ng/mL
      limit of detection. The high performance and distinct spectral features of this
      metal-insulator-metal plasmonic nanocup array make this device promising for
      future portable optical sensing systems with minimal instrumentation
      requirements.

PMID- 29380596
TI  - 99mTc-Labeled RGD-Polyethylenimine Conjugates with Entrapped Gold Nanoparticles
      in the Cavities for Dual-Mode SPECT/CT Imaging of Hepatic Carcinoma.
AB  - We report the construction and characterization of 99mTc-labeled arginine-glycine
      aspartic acid (RGD)-polyethylenimine (PEI) conjugates with entrapped gold
      nanoparticles in the cavities (RGD-99mTc-Au PENPs) for dual-mode single-photon
      emission computed tomography (SPECT)/computed tomography (CT) imaging of an
      orthotopic hepatic carcinoma model. In this study, PEI was successively decorated
      with diethylenetriaminepentaacetic acid, poly(ethylene glycol) (PEG), and
      PEGylated RGD segments, and was utilized as an effective nanoplatform to entrap
      Au NPs and to be labeled with 99mTc. We showed that the designed RGD-99mTc-Au
      PENPs displayed desirable colloidal stability and radiostability, and
      cytocompatibility in the investigated concentration range, and could be
      specifically uptaken by alphavbeta3 integrin-overexpressing liver cancer cells in
      vitro. In vivo CT and SPECT imaging results indicated that the particles were
      able to be accumulated within an orthotopic hepatic carcinoma and displayed both
      CT and SPECT contrast enhancement in the tumor tissue. With the proven
      biocompatibility in vivo via histological examinations, the designed RGD-99mTc-Au
      PENPs may be potentially employed as an effective nanoprobe for a highly
      efficient dual-mode SPECT/CT imaging of various alphavbeta3 integrin
      overexpressing tumors.

PMID- 29380597
TI  - From Production to Consumption: A Coupled Human-Environmental Nitrogen Flow
      Analysis in China.
AB  - Anthropogenic inputs of reactive nitrogen (Nr) provide sufficient food, energy,
      and industrial products to meet human demands; however, only a fraction of Nr is
      consumed as food and nonfood goods, and the rest is lost to the environment and
      negatively affects ecosystems. High-resolution studies of nitrogen flows are
      invaluable to increase nitrogen use efficiencies and reduce environmental
      emissions. In this study, a comprehensive substance flow analysis of nitrogen for
      China in 2014 is presented. Based on the conceptual framework, which highlights
      the key roles of human drivers, the analysis of the synthetic ammonia supply and
      demand balance shows that 75% of ammonia is used for agricultural purposes.
      Moreover, the life cycle analysis of food nitrogen shows that human food
      consumption accounts for approximately 7% of the total Nr inputs. A quantitative
      analysis of pollutant emissions shows that industrial and crop production are the
      main sources of atmospheric emissions, while livestock farming and crop
      production are the main sources of water emissions. Finally, we investigate four
      scenarios (efficiency improvement, high recycling rate, nitrogen oxide emission
      reduction, and a combined scenario) and provide relevant policy recommendations
      (large farm size, standardized agricultural production model, flue gas
      denitration, etc.) for improving nitrogen management practices.

PMID- 29380598
TI  - Proposal of a Linear Retention Index System for Improving Identification
      Reliability of Triacylglycerol Profiles in Lipid Samples by Liquid Chromatography
      Methods.
AB  - The retention index system was proposed in 1958 by Kovats. It is based on the
      correlation between the retention time of the analytes and the ones of a series
      of reference standards, making retention data dependent on the chromatographic
      phenomenon only, viz., on the three-term interaction analyte-stationary phase
      mobile phase. Particularly in GC, because the mobile phase has a negligible
      influence, the retention of the analytes depends almost entirely on the
      stationary phase and it is as independent as possible from operating conditions.
      This makes retention index databases usable in samples identification at both the
      intra- and interlaboratory levels. The scope of this research was to create a
      similar identification system in LC, where the identification of unknowns is
      still a challenge because of the unavailability of spectral databases related to
      the low reproducibility of mass spectra generated by means of the atmospheric
      pressure ionization technique normally interfaced to LC. Lipid compounds,
      specifically triacylglycerols, were selected as target analytes mainly due to
      their regular chromatographic LC profile under reversed phase conditions. The odd
      carbon chain number triacylglycerol series from trinonain to trinonadecanoin was
      chosen as the basis of the retention index scale and a database of 209
      triacylglycerols was built. For this purpose an ultra high-performance LC method,
      able to maximize the baseline separation of triacylglycerols in different real
      world samples (vegetable oils, fish, and milk samples) was developed.

PMID- 29380599
TI  - Enzymatic Formation of an Injectable Hydrogel from a Glycopeptide as a Biomimetic
      Scaffold for Vascularization.
AB  - The construction of functional vascular networks in regenerative tissues is a
      crucial technology in tissue engineering to ensure the sufficient supply of
      nutrients. Although natural hydrogels are highly prevalent in fabricating three
      dimensional scaffolds to induce neovascular growth, their widespread
      applicability was limited by the potential risk of immunogenicity or pathogen
      transmission. Therefore, developing hydrogels with good biocompatibility and cell
      affinity is highly desirable for fabricating alternative matrices for tissue
      regeneration applications. Herein, we report the generation of a new kind of
      hydrogel from supramolecular assembling of a synthetic glycopeptide to mimic the
      glycosylated microenvironment of extracellular matrix. In the presence of a
      tyrosine phosphate group, this molecule can undergo supramolecular self
      assembling and gelation triggered by alkaline phosphatase under physiological
      conditions. Following supramolecular self-assembling, the glycopeptide gelator
      tended to form nanofilament structures displaying a high density of glucose
      moieties on their surface for endothelial cell adhesion and proliferation. On
      further incorporation with deferoxamine (DFO), the self-assembled hydrogel can
      serve as a reservoir for sustainably releasing DFO and inducing endothelial cell
      capillary morphogenesis in vitro. After subcutaneous injection in mice, the
      glycopeptide hydrogel encapsulating DFO can work as an effective matrix to
      trigger the generation of new blood capillaries in vivo.

PMID- 29380600
TI  - Bioinspired Supramolecular Lubricating Hydrogel Induced by Shear Force.
AB  - Bioinspired lubricating materials are great challenge toward artificial joints.
      In this contribution, we synthesize a bioinspired hydrogel by combining a
      thixotropic supramolecular network and polymer double network, exhibiting a
      unique shear-responsive lubricating property. The disassembly of the N
      fluorenylmethoxycarbonyl-l-tryptophan supramolecular network triggered by shear
      force will endow lubricating function to the hydrogel; meanwhile PAAm and PVA
      double network acts as the supporting skeleton with high mechanical property.
      This work will bring new insight on the design of artificial lubricating joint.

PMID- 29380601
TI  - Fiber-Optic Bio-sniffer (Biochemical Gas Sensor) Using Reverse Reaction of
      Alcohol Dehydrogenase for Exhaled Acetaldehyde.
AB  - Volatile organic compounds (VOCs) exhaled in breath have huge potential as
      indicators of diseases and metabolisms. Application of breath analysis for
      disease screening and metabolism assessment is expected since breath samples can
      be noninvasively collected and measured. In this research, a highly sensitive and
      selective biochemical gas sensor (bio-sniffer) for gaseous acetaldehyde (AcH) was
      developed. In the AcH bio-sniffer, a reverse reaction of alcohol dehydrogenase
      (ADH) was employed for reducing AcH to ethanol and simultaneously consuming a
      coenzyme, reduced form of nicotinamide adenine dinucleotide (NADH). The
      concentration of AcH can be quantified by fluorescence detection of NADH that was
      consumed by reverse reaction of ADH. The AcH bio-sniffer was composed of an
      ultraviolet light-emitting diode (UV-LED) as an excitation light source, a
      photomultiplier tube (PMT) as a fluorescence detector, and an optical fiber
      probe, and these three components were connected with a bifurcated optical fiber.
      A gas-sensing region of the fiber probe was developed with a flow-cell and an ADH
      immobilized membrane. In the experiment, after optimization of the enzyme
      reaction conditions, the selectivity and dynamic range of the AcH bio-sniffer
      were investigated. The AcH bio-sniffer showed a short measurement time (within 2
      min) and a broad dynamic range for determination of gaseous AcH, 0.02-10 ppm,
      which encompassed a typical AcH concentration in exhaled breath (1.2-6.0 ppm).
      Also, the AcH bio-sniffer exhibited a high selectivity to gaseous AcH based on
      the specificity of ADH. The sensor outputs were observed only from AcH-contained
      standard gaseous samples. Finally, the AcH bio-sniffer was applied to measure the
      concentration of AcH in exhaled breath from healthy subjects after ingestion of
      alcohol. As a result, a significant difference of AcH concentration between
      subjects with different aldehyde dehydrogenase type 2 (ALDH2) phenotypes was
      observed. The AcH bio-sniffer can be used for breath measurement, and further, an
      application of breath analysis-based disease screening or metabolism assessment
      can be expected due to the versatility of its detection principle, which allows
      it to measure other VOCs by using NADH-dependent dehydrogenases.

PMID- 29380602
TI  - Resource Demand Scenarios for the Major Metals.
AB  - The growth in metal use in the past few decades raises concern that supplies may
      be insufficient to meet demands in the future. From the perspective of historical
      and current use data for seven major metals-iron, manganese, aluminum, copper,
      nickel, zinc, and lead-we have generated several scenarios of potential metal
      demand from 2010 to 2050 under alternative patterns of global development. We
      have also compared those demands with various assessments of potential supply to
      midcentury. Five conclusions emerge: (1) The calculated demand for each of the
      seven metals doubles or triples relative to 2010 levels by midcentury; (2) The
      largest demand increases relate to a scenario in which increasingly equitable
      values and institutions prevail throughout the world; (3) The metal recycling
      flows in the scenarios meet only a modest fraction of future metals demand for
      the next few decades; (4) In the case of copper, zinc, and perhaps lead, supply
      may be unlikely to meet demand by about midcentury under the current use patterns
      of the respective metals; (5) Increased rates of demand for metals imply
      substantial new energy provisioning, leading to increases in overall global
      energy demand of 21-37%. These results imply that extensive technological
      transformations and governmental initiatives could be needed over the next
      several decades in order that regional and global development and associated
      metal demand are not to be constrained by limited metal supply.

PMID- 29380603
TI  - Enantioselective Trapping of Oxonium Ylides by 3-Hydroxyisoindolinones via a
      Formal SN1 Pathway for Construction of Contiguous Quaternary Stereocenters.
AB  - An enantioselective Rh(II)/chiral phosphoric acid co-catalyzed three-component
      reaction via trapping of oxonium ylides with 3-hydroxyisoindolinones by a formal
      SN1 pathway is described. This reaction allows for the efficient synthesis of
      isoindolinone derivatives with two contiguous quaternary stereogenic centers in
      high yields (up to 93%) with excellent enantioselectivities and moderate
      diastereoselectivities under mild reaction conditions.

PMID- 29380604
TI  - Ruthenium-Catalyzed Hydrogenation of Carbocyclic Aromatic Amines: Access to
      Chiral Exocyclic Amines.
AB  - The first highly enantioselective hydrogenation of carbocyclic aromatic amines
      has been successfully realized using in situ-generated chiral ruthenium complex
      as catalyst, affording facile access to chiral exocyclic amines with up to 98%
      ee.

PMID- 29380605
TI  - Click, Release, and Fluoresce: A Chemical Strategy for a Cascade Prodrug System
      for Codelivery of Carbon Monoxide, a Drug Payload, and a Fluorescent Reporter.
AB  - A chemical strategy was developed wherein a single trigger sets in motion a three
      reaction cascade leading to the release of more than one drug-component in
      sequence with the generation of a fluorescent side product for easy monitoring.
      As a proof of concept, codelivery of CO with the antibiotic metronidazole was
      demonstrated.

PMID- 29380606
TI  - Ferroelectric Control of the Spin Texture in GeTe.
AB  - The electric and nonvolatile control of the spin texture in semiconductors would
      represent a fundamental step toward novel electronic devices combining memory and
      computing functionalities. Recently, GeTe has been theoretically proposed as the
      father compound of a new class of materials, namely ferroelectric Rashba
      semiconductors. They display bulk bands with giant Rashba-like splitting due to
      the inversion symmetry breaking arising from the ferroelectric polarization, thus
      allowing for the ferroelectric control of the spin. Here, we provide the
      experimental demonstration of the correlation between ferroelectricity and spin
      texture. A surface-engineering strategy is used to set two opposite predefined
      uniform ferroelectric polarizations, inward and outward, as monitored by
      piezoresponse force microscopy. Spin and angular resolved photoemission
      experiments show that these GeTe(111) surfaces display opposite sense of
      circulation of spin in bulk Rashba bands. Furthermore, we demonstrate the
      crafting of nonvolatile ferroelectric patterns in GeTe films at the nanoscale by
      using the conductive tip of an atomic force microscope. Based on the intimate
      link between ferroelectric polarization and spin in GeTe, ferroelectric
      patterning paves the way to the investigation of devices with engineered spin
      configurations.

PMID- 29380607
TI  - Measuring Microtubule Supertwist and Defects by Three-Dimensional-Force-Clamp
      Tracking of Single Kinesin-1 Motors.
AB  - Three-dimensional (3D) nanometer tracking of single biomolecules provides
      important information about their biological function. However, existing
      microscopy approaches often have only limited spatial or temporal precision and
      do not allow the application of defined loads. Here, we developed and applied a
      high-precision 3D-optical-tweezers force clamp to track in vitro the 3D motion of
      single kinesin-1 motor proteins along microtubules. To provide the motors with
      unimpeded access to the whole microtubule lattice, we mounted the microtubules on
      topographic surface features generated by UV-nanoimprint lithography. Because
      kinesin-1 motors processively move along individual protofilaments, we could
      determine the number of protofilaments the microtubules were composed of by
      measuring the helical pitches of motor movement on supertwisted microtubules.
      Moreover, we were able to identify defects in microtubules, most likely arising
      from local changes in the protofilament number. While it is hypothesized that
      microtubule supertwist and defects can severely influence the function of motors
      and other microtubule-associated proteins, the presented method allows for the
      first time to fully map the microtubule lattice in situ. This mapping allows the
      correlation of motor-filament interactions with the microtubule fine-structure.
      With the additional ability to apply loads, we expect our 3D-optical-tweezers
      force clamp to become a valuable tool for obtaining a wide range of information
      from other biological systems, inaccessible by two-dimensional and/or ensemble
      measurements.

PMID- 29380608
TI  - Enzymatic Synthesis of GDP-alpha-l-fucofuranose by MtdL and Hyg20.
AB  - Two mutases, MtdL and Hyg20, are reported. Both are able to functionally drive
      the biosynthesis of GDP-alpha-l-fucofuranose. Both enzymes catalyze similar
      functions, catalytically enabling the bidirectional reaction between GDP-beta-l
      fucopyranose and GDP-alpha-l-fucofuranose using only divalent cations as
      cofactors. This realization is but one of a number of important insights into
      fucofuranose biosynthesis presented herein.

PMID- 29380609
TI  - Staying true to our values.
AB  - With the JCR published last summer, the IF of the EJPD reached 0.683! This is the
      highest value that the journal has ever reached and it shows a clear progression
      compared to the 2015 value of 0.421. This event, occurred shortly after the death
      of professor Giuliano Falcolini, led me to reflect and read again his editorial
      published in the issue N.3, 2011 of the EJPD. In that editorial professor
      Falcolini communicated with joy and enthusiasm ( ... we were honoured and
      thrilled to see our European Journal of Paediatric Dentistry included in the list
      ...) to the whole dental scientific world that the journal had been awarded the
      IF (the editorial can be read in full at http://www.ejpd.eu/bibliografia_detail.
      asp? id=399). I believe that reading again what he wrote at the time is the best
      way to remember him and to be aware of the solid foundations that professor
      Falcolini has laid in order to succeed both as journal and scientific society.
      The enthusiasm, joy, and desire to do well, together with the rigorous scientific
      competence with which professor Falcolini led the EJPD in those years are the
      same values that the whole SIOI group will continue to follow in order to reach
      new and higher goals.

PMID- 29380610
TI  - In vitro performance of ultrasound enamel preparation compared with classical bur
      preparation on pit and fissure sealing.
AB  - AIM: Fissure sealants are effective in preventing caries. The aim of this in
      vitro study was to evaluate the effects of two different enamel surface
      preparation techniques for pit and fissure sealing. MATERIALS AND METHODS: Sixty
      extracted sound third molars were used. For each tooth, the mesial half of the
      occlusal fissures was treated with ultrasound diamond tip T1 mounted on an
      ultrasonic handpiece, while the distal half with conventional diamond bur. The
      teeth were randomly divided into 2 groups (n = 30/each). Group 1 samples were
      stored in distilled water at 4  degrees C. For group 2 samples, sealing of
      occlusal fissures was performed according to standard procedures. Bucco-lingual
      cuts parallel to the long axis of the tooth were made in order to separate the
      two different types of preparations. The effects of the executed procedures were
      assessed with SEM. RESULTS: Surfaces prepared with ultrasound system showed the
      presence of residual debris and appeared more irregular than surfaces prepared
      with traditional bur system. Furthermore, images showed the presence of cracks on
      the bottom and on the walls of the ultrasound prepared fissures. CONCLUSION:
      Conventional bur surface treatment showed a better performance when compared to
      ultrasound preparation and could probably ensure superior sealant retention.

PMID- 29380611
TI  - Evaluation of the relationship between obesity, dental caries and periodontal
      disease in adolescents.
AB  - AIM: To assess the prevalence of caries, oral hygiene quality and periodontal
      disease in a cohort of obese adolescents compared to a control group. MATERIALS
      AND METHODS: Study Design: cross-sectional study conducted on 204 subjects (age
      range 10-16 years). Ninety obese subjects (BMI >90) and 114 normal-weight
      subjects (BMI <75) were visited at the Bambino Gesu Children's Hospital and in a
      junior high school in Rome, respectively. An ad hoc questionnaire (investigating
      demographic and oral health behaviour data) was filled in by patients and their
      caregivers. Accurate oral examinations were conducted. The Decayed-Missing-Filled
      Teeth/Surfaces Index in both permanent (DMFT/DMFS) and primary dentition
      (dmft/dmfs), Gingival Bleeding Index (GBI), Visible Plaque Index (VPI), and
      Probing Depth (PD) were recorded. STATISTICS: data analysis was carried out using
      the Statistical Package for the Social Sciences (SPSS 21.0; SPSS IBM, New York,
      NY). The data of the two groups were compared by means of Student's t Test or the
      Mann-Whitney test for numerical data and the Chi-square test for categorical
      data. RESULTS: Patients affected by obesity, compared with controls, presented
      less compromised teeth in the primary dentition (dmft obese: 0.30 &#177;+/- 1.12;
      normal-weight: 1.00 &#177; 1.90; P<0.001) and less compromised dental surfaces
      (dmfs obese: 0.51 &#177; 2.14; normal-weight: 1.61 &#177; 3.10; P<0.001).
      Furthermore obese patients showed minor gingival inflammation with less bleeding
      on probing (GBI) (obese: 23.95 &#177; 21.43; normal-weight: 38.17&#177; 24.37;
      P<0.001), and less probing depth in a greater number of sites (PPD &#8804; 3)
      (obese: 101.92 &#177; 9.27; normal-weight: 97.28 &#177; 12.13; P<0.001).
      Moreover, the obese group showed a better oral hygiene (VPI) (obese: 25.69
      &#177;25.83; normal-weight: 37.72 &#177;24.34; P<0.001). CONCLUSION: In our
      study, obese adolescents showed a better oral hygiene, fewer compromised teeth
      and better periodontal health when compared with normal-weight patients.

PMID- 29380612
TI  - Analysis of clinical studies related to apexification techniques.
AB  - AIM: The aim of this study was to gather all the clinical studies regarding
      apexification and artificial apical barrier techniques, point out the possible
      differences of the clinical procedures and investigate how these are changing
      over time. MATERIALS AND METHODS: An electronic search was carried out in PubMed,
      covering the period from March 1968 to July 2015. More articles were retrieved by
      hand-searching or by the reference section of the included articles. Specific
      criteria were set in order to determine the relevance of each study. RESULTS: One
      hundred and thirty eight articles were included, 53% of them concerned
      apexification with MTA plug. Long term apexification studies demonstrated 13% for
      a single change of the intracanal medicament and 85% for two or more. In 13% of
      the studies concerning artificial apical plug, the procedure included a single
      visit. Calcium hydroxide was left in the root canal for 3-12 months in 59% of the
      long term apexification studies, for 12-24 in 42% and for 24 months or more in
      10%. CONCLUSION: Both techniques can lead to favourable clinical outcomes. There
      is a tendency for the artificial apical barrier apexification over the years,
      which usually includes the use of intracanal medicament for a short time.

PMID- 29380613
TI  - Evaluation of antibiotic mix in Non-instrumentation Endodontic Treatment of
      necrotic primary molars.
AB  - AIM: To compare the clinical and radiographic success rates of an antibiotic mix
      consisting of metronidazole, minocycline and ciprofloxacin (3Mix-MP) and another
      mix where minocycline was replaced with clindamycin (3Mix-MP-R) in non
      instrumentation endodontic treatment (NIET) of necrotic primary molars and to
      determine the effect of root resorption on the success of the treatment.
      MATERIALS AND METHODS: Forty-two necrotic mandibular primary molars from 22
      healthy children were randomly assigned to either mixture. Blinded clinical
      evaluation was conducted after 1, 3, 6 and 12 months by the operator, and blinded
      radiographic evaluation was conducted at 6 and 12 months follow-ups by other two
      investigators with inter-examiner reproducibility of 0.95. RESULTS: Overall
      success rates of 3Mix-MP and 3Mix-MP-R were 80.96% and 76.20% respectively, with
      no statistically significant difference. Radiographically, resorption of more
      than one third of the root length had a lower failure rate with no statistically
      significant difference (p<0.5). CONCLUSION: Primary teeth with necrotic pulp can
      be treated with 3Mix-MP or 3Mix-MP-R irrespective of the degree of root
      resorption.

PMID- 29380614
TI  - Pharyngeal airway changes in pre-pubertal children with Class II malocclusion
      after Frankel-2 treatment.
AB  - AIM: To evaluate two-dimensional changes in pharyngeal airway dimensions in pre
      pubertal children with a Class II malocclusion treated with a Fr&#228;nkel-2
      appliance compared to a matched non-treated control sample. MATERIALS AND
      METHODS: Lateral cephalograms obtained from 28 consecutively treated pre-pubertal
      children before (T0) and after (T1) a one-year Fr&#228;nkel-2 treatment were
      analysed. Fr&#228;nkel-2 appliance was used for at least 18 hr/day during 12
      months. The control group was matched as closely as possible. All the cases
      presented normal facial growth pattern. Sagittal and vertical cephalometric
      measurements assessing maxillary and mandibular skeletal positions, as well as
      sagittal pharyngeal airway dimensions, were calculated. Intraclass correlation
      coefficient was calculated in order to determine reliability. Differences based
      on age for all the outcome variables at T0 were compared with an independent t
      test. A MANOVA was used thereafter to determine if any factors and their
      interactions were associated with changes in the outcome variables. Differences
      between T1 and T0 were evaluated with either a t-student test or a Mann Whitney U
      test. RESULTS: At T0 differences between groups were noted for several variables.
      These differences were considered during the follow-up statistical analysis.
      Changes between groups after treatment (T1-T0) were noted for SNB, PNS to Ba,
      McNamara Low and Middle to S (increase in treatment group), and ANB and AD1 to Ba
      (decrease in treatment group). CONCLUSIONS: Some pharyngeal two-dimensional
      airway dimensions changed in Class II malocclusion pre-pubertal patients during a
      one-year treatment with Fr&#228;nkel-2 appliances.

PMID- 29380615
TI  - External Cervical Resorption: a case report.
AB  - AIM: External cervical resorption is a form of root resorption which begins in
      the cervical region of the tooth and spreads out in the thickness of the dentin
      in an irregular way; clinically, it may be not visible and, as it is generally
      asymptomatic before involvement of the pulp, it is often an occasional finding in
      radiographic examination. Several factors are related to its aetiology. This
      paper reports a case of external cervical resorption in a mandibular right first
      molar of a 17-year-old patient; the tooth was extracted and histological analysis
      was performed. MATERIALS AND METHODS: Radiographic examination showed a
      progressive external cervical resorption of the lower right first molar;
      extension of the lesion and pulp involvement indicated tooth extraction; the
      sample underwent histological analysis. RESULTS: The histological study confirmed
      the presence of vascular connective tissue in the resorptive lacunae, invading
      the dentin from the external surface of the root, and perforations from the
      defect into the pulp; it was also noticed the presence of bone-like tissue.

PMID- 29380616
TI  - Effects of rapid vs slow maxillary expansion on nasal cavity dimensions in
      growing subjects: a methodological and reproducibility study.
AB  - AIM: To evaluate the methodological feasibility of a RCT comparing skeletal
      changes of nasal cavity size obtained with RME and SME, assessed via CBCT.
      MATERIALS AND METHODS: Twenty Caucasian children with a mean age of 10.4 years
      were recruited and allocated to receive RME (10 subjects, mean age 10.4 years) or
      SME (10 subjects, mean age 10.5 years). INCLUSION CRITERIA: constricted maxillary
      arch, upper and lower first molars erupted, unilateral or bilateral posterior
      crossbite. EXCLUSION CRITERIA: age above 15 years, history of previous
      orthodontic treatment, periodontal disease, systemic disease affecting
      craniofacial growth, or craniofacial congenital syndrome. CBCT examinations were
      performed before treatment (T0) and 7 months after expander removal (T1). Changes
      of nasal width (NW), palatal width (PW) and total nasal volume (TNV) were
      assessed; palatal and nasal expansion was also calculated as a percentage of the
      increase of intermolar width IMW (PW% and NW%). RESULTS: The correlation between
      the first and the second readings ranged from 0.991 to 0.995 for linear
      measurements and was of 0.915 for volumetric measurements. The method error, as
      described by the value of ?, was in general less than 0.3 mm for linear
      measurements and 0.372 cm&#179; for volumetric measurements. All linear
      transverse skeletal and dental measurements and the nasal volume increased with
      both RME and SME protocols. CONCLUSION: The reported methodology can be
      reasonably used to investigate the transverse dimension of nasal cavity. The PW%
      and NW% parameters more accurately described the efficacy of the two expansion
      protocols as compared to their corresponding absolute measurement (PW and NW).

PMID- 29380617
TI  - Reliability and validity of the Italian versions of the Children's Fear Survey
      Schedule - Dental Subscale and the Modified Child Dental Anxiety Scale.
AB  - AIM: Children's dental fear and anxiety (DFA) causes significant problems in
      clinical practice. The 15-item Children's Fear Survey Schedule - Dental Subscale
      (CFSS-DS) and the 8-item Modified Child Dental Anxiety Scale (MCDAS) are the most
      widely used measures of dental fear in children. The aim of this study is to
      examine the reliability and validity of the Italian versions of the CFSS-DS and
      MCDAS, also in comparison with a simple visual analogue scale (VAS). MATERIALS
      AND METHODS: The CFSS-DS and MCDAS were translated into Italian by a consensus
      panel of experts and administered to 210 dental patients aged 4-11 years from
      three Italian Institutions. Internal reliability was assessed using the
      Cronbach's alpha correlation. A sub-sample of 60 children was selected for test
      retest analysis. CFSS-DS and MCDAS, plus a VAS scale, rated both by children and
      parents, were validated using as gold standard the 4-item Frankl scale for
      behaviours assessed by dentists. RESULTS: Mean CFSS-DS score was 30.8 (SD: 11.1)
      and mean MCDAS score was 17.9 (SD: 7.2), significantly higher among children aged
      4-7 years and among children at their first dental visit. The alpha value for
      internal reliability was 0.90 (95%, CI= 0.88-0.92) for CFSS-DS and 0.87 (95%
      CI=0.85-0.90) for MCDAS. Both CFSS-DS and MCDAS showed good test-retest
      reliability (rsp= 0.80; p<0.001 for both scales). CFSS-DS and MCDAS predicted a
      Frankl score &#8804;2 (i.e., indicating children with an uncooperative behaviour)
      with a fair accuracy (AUC=0.69 and AUC=0.68, respectively). The VAS scale was
      more effective in predicting a negative behaviour (AUC=0.78). The scales self
      reported by children were only slightly more accurate than those reported by
      parents. CONCLUSION: The Italian versions of the CFSS-DS and MCDAS are valid and
      reliable tools for the assessment of dental fear in Italian children aged 4-11
      years. A simple, one-item VAS, and dental fear and anxiety evaluation by parents
      may be valid and quick alternatives to multi-item indices to predict an
      uncooperative children behaviour.

PMID- 29380618
TI  - Reasons of repeat dental treatment under general anaesthesia: A retrospective
      study.
AB  - AIM: The purpose of this chart review study was to investigate the common factors
      that exist in paediatric patients requiring a repeat dental treatment under
      general anaesthesia (GA2) within four years after the initial dental treatment
      under general anaesthesia (GA1). MATERIALS AND METHODS: The Electronic Health
      Records of one to 12 year-old children who received dental treatment under
      general anaesthesia (GA) between April 2004 and October 2009 were identified and
      analysed by a single examiner. Children who had GA2, within a four year period
      following GA1 were categorised as cases. Children who had only one dental
      treatment under GA were considered the control pool. Each case was matched to
      three controls based on sex and age range at GA1 of &#177; 6 months. Other
      recorded variables included: date of birth, date of GAs (GA1 and GA2 for cases;
      GA1 for controls), type of payment, dmfs before GA1, dental treatments provided
      under GA, return of 1-week post-GA1 follow-up, frequency of recare/recall visits
      following one-year post-GA1 visit and the type and frequency of post GA1
      emergency visits. RESULTS: Out of 581 subjects, 29 (4.99%) cases were matched to
      87 controls. Medically compromised patients had four times the risk of GA2. At
      GA1, cases received statistically significant less sealants (p=0.026), less
      extractions (p<0.0001), and more composite restorations (p=0.0002) compared to
      controls. CONCLUSION: Medically compromised children and children treated with
      more composites and fewer sealants and extractions at their initial dental
      treatment under general anaesthesia were more likely to have a repeat dental
      treatment under general anaesthesia within 4 years.

PMID- 29380619
TI  - The prevalence of ankyloglossia in 302 newborns with breastfeeding problems and
      sucking difficulties in Barcelona: a descriptive study.
AB  - AIM: Oral and maxillofacial development is influenced by the lingual frenulum and
      also affects breathing, occlusion, sucking, swallowing, speech, among others.
      Ankyloglossia in the newborn may result in breastfeeding difficulties: maternal
      nipple pain and/or erosion or mastitis, poor weight gain and excessively long
      breastfeeds. The main objective of this work is to study the prevalence of
      ankyloglossia in newborns with breastfeeding difficulties. MATERIALS AND METHODS:
      This is a transversal descriptive study of 302 patients, between 0 and 6 months,
      who attended the hospital as a result of breastfeeding difficulties. All patients
      with sucking problems and ankyloglossia were included in this study and followed
      the multidisciplinary treatment protocol made up of the services of
      Breastfeeding, Speech Therapy and Orofacial Rehabilitation and Oral and
      Maxillofacial Surgery. RESULTS: 1,102 newborns were seen at the paediatric
      service of Hospital de Nens, Barcelona (Spain) during 2 years; 302 had
      breastfeeding difficulties and of these, 171 were diagnosed with ankyloglossia
      (60 girls and 111 boys). Coryllos Grade 3 ankyloglossia was the most prevalent
      (59.6%) type; 85 infants (49.7%) were exclusively breastfed and 26 (50.35%) were
      mixed fed (formula and breastfeeding). Only 43 patients had a family history of
      tongue-tie (25.1%). CONCLUSION: Ankyloglossia linked to breastfeeding
      difficulties must be treated by a multidisciplinary team. We have found a high
      prevalence of the condition since the population studied are newborns with
      sucking problems. If a frenotomy is necessary, we recommend stimulating suction
      with myofunctional therapy before and after surgery to avoid scar retraction.

PMID- 29380620
TI  - Parental Oral Health Literacy of children with severe early childhood caries in
      Hong Kong.
AB  - AIM: To assess the parental oral health literacy of children with severe early
      childhood caries. MATERIALS AND METHODS: A total of 315 children diagnosed with
      severe early childhood caries, and their parents were recruited to participate in
      the study. A clinical examination was conducted to assess the children's oral
      health status. Their parents were asked to complete a Hong Kong Oral Health
      Literacy Assessment Task for Paediatric Dentistry (HKOHLAT-P) questionnaire.
      RESULTS: There were 311 complete responses (98.7% response rate). The mean age of
      children was 4.7 years (standard deviation (SD) =0.8). The mean decayed, missing
      filled teeth (dmft) score was 10.2 (SD = 4.5). Most of the children had unfilled
      dental caries (98.7%). About 72.7% of the parents had an education level of up to
      secondary school. More than half (61.7%) had a monthly family income of below HKD
      20,000. Parents with a lower education level and income had a significantly lower
      HKOHLAT-P score (p<0.001). Multiple regression analyses showed that a higher
      family income (p<0.05) and education level (p<0.05) predicted higher HKOHLAT-P
      scores. CONCLUSION: The parental oral health literacy of children with severe
      early childhood caries was associated with their socio-economic background. Oral
      health education should be targeted towards the lower socio-economic groups.

PMID- 29380621
TI  - Paediatric laser dentistry. Part 4: Soft tissue laser applications.
AB  - AIM: Lasers can provide effective soft tissues applications in children. All the
      wavelengths produce incision and vaporisation of oral tissues, together with a
      high bactericidal effect. The haemosthatic effect varys according to the
      wavelength used, and the choice of a visibile, near, medium or far infrared laser
      allows a better interaction with specific targets, gingiva, mucosa, frenum, or
      oral pathology.

PMID- 29380623
TI  - Improved cookstoves and their effect on carbon monoxide levels in San Lucas
      Toliman, Guatemala.
AB  - INTRODUCTION: Installation of ventilated cookstoves has been shown to improve 24
      h carbon monoxide (CO) and particulate exposure in the Guatemalan highlands.
      However, a survey of villagers around San Lucas Toliman found much higher than
      expected CO levels. Our purpose is to evaluate the effects of improved cookstoves
      on CO levels in these villagers. METHODS: This is cross sectional observational
      study in six rural communities. Blood carboxyhemoglobin (SpCO) was measured at
      three different times during the day. Stove type and location, as well as any
      respiratory, eye, or general symptoms reported were recorded. RESULTS: 122
      patients were included. CO levels were much higher than would be expected in a
      non-smoking population, with an average level of 4.6 +/- 2.3 percent. There was
      no significant correlation in CO level and stove type or in CO level and time of
      day. Reported frequency of respiratory and eye symptoms (dyspnea, p = 0.03;
      cough, p = 0.01; burning eyes, p = 0.001; and excessive tearing, p = 0.001) did
      vary significantly between improved and unimproved stove groups. CONCLUSION: This
      study found high average SpCO levels in all villagers. This suggests that some
      contributor other than cookstoves may be an additional driver of individual CO
      exposure in this area.

PMID- 29380624
TI  - Having a Regular Primary Care Provider Is Associated With Improved Markers of
      Well-Being Among Children With Attention-Deficit Hyperactivity Disorder.
AB  - We examined the association between having a regular primary care physician (PCP)
      and measures of flourishing and academic success in children with attention
      deficit hyperactivity disorder (ADHD). We performed a cross-sectional study using
      data from the 2011-2012 National Survey of Children's Health. Children aged 6 to
      17 years with a diagnosis of ADHD were included in the study (n = 8173). The
      exposure was whether the guardian identified a regular PCP for their child. The
      outcomes were parental-reported measures of child well-being and academic
      performance. Among the study population, 8.9% reported no regular PCP. These
      children were found to be significantly less likely to finish assigned tasks
      (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.35-0.79), care
      about school (adjusted OR = 0.62, 95% CI = 0.38-0.92), and finish homework
      (adjusted OR = 0.58, 95% CI = 0.36-0.88). There were no differences in other
      examined outcomes. Enhancing longitudinal care for this population may optimize
      their academic performance.

PMID- 29380622
TI  - Atropisomerism in medicinal chemistry: challenges and opportunities.
AB  - Atropisomerism is a dynamic type of axial chirality that is ubiquitous in
      medicinal chemistry. There are several examples of stable atropisomeric US FDA
      approved drugs and experimental compounds, and in each case the atropisomers of
      these compounds possess drastically different biological activities. Rapidly
      interconverting atropisomerism is even more prevalent, and while such compounds
      are typically considered achiral, they bind their protein targets in an
      atroposelective fashion, with the nonrelevant atropisomer contributing little to
      the desired activities. It has been recently demonstrated that various properties
      of an interconverting atropisomer can be modulated through the synthesis of
      atropisomer stable and pure analogs. Herein we discuss examples of atropisomerism
      in drug discovery as well as challenges and opportunities moving forward.

PMID- 29380625
TI  - Design, synthesis and evaluation of 1,4-benzodioxine derivatives as novel
      platelet aggregation inhibitors.
AB  - AIM: To find novel platelet aggregation inhibitors, two new series of 1,4
      benzodioxine derivatives were synthesized and screened for the ability to inhibit
      platelet aggregation. MATERIALS & METHODS: The synthesized compounds were
      evaluated for antiplatelet aggregation activity using human blood platelet and
      GPIIb/IIIa antagonistic activity. RESULTS: Compound 9-2p showed significant
      antiplatelet activity with the IC50 values of 41.7 and 22.2 MUM induced by ADP
      and thrombin, respectively, more potent than that of LX2421. Compound 9-2p
      exhibited GPIIb/IIIa antagonistic activity with the IC50 value of 2.3 MUM, as
      potent as RGDs. In vivo study showed that 9-2p displayed remarkable
      antithrombotic activity, more effective than LX2421, but less effective than
      tirofiban. CONCLUSION: Compound 9-2p showed moderate antiplatelet activity and
      antithrombotic activity, which could be further optimized based on the target of
      GPIIb/IIIa.

PMID- 29380626
TI  - Does message framing affect changes in behavioural intentions in people with
      psoriasis? A randomized exploratory study examining health risk communication.
AB  - Message framing is important in health communication research to encourage
      behaviour change. Psoriasis, a long-term inflammatory skin condition, has
      additional comorbidities including high levels of anxiety and cardiovascular
      disease (CVD), making message framing particularly important. This experimental
      study aimed to: (1) identify whether health messages about psoriasis presented as
      either gain- or loss-framed were more effective for prompting changes in
      behavioural intentions (BI), (2) examine whether BI were driven by a desire to
      improve psoriasis or reduce CVD risk; (3) examine emotional reactions to message
      frame; and (4) examine predictors of BI. A two by two experiment examined the
      effects on BI of message frame (loss vs. gain) and message focus (psoriasis
      symptom reduction vs. CVD risk reduction). Participants with psoriasis (n = 217)
      were randomly allocated to one of four evidence-based health messages related to
      either smoking, alcohol, diet or physical activity, using an online
      questionnaire. BI was the primary outcome. Analysis of variance tests and
      hierarchical multiple regression analyses were conducted. A significant frame by
      focus interaction was found for BI to reduce alcohol intake (p = .023); loss
      framed messages were more effective for CVD risk reduction information, whilst
      gain-framed messages were more effective for psoriasis symptom reduction
      information. Message framing effects were not found for BI for increased physical
      activity and improving diet. High CVD risk was a significant predictor  of
      increased BI for both alcohol reduction (beta = .290, p < .01) and increased
      physical activity (beta = -.231, p < .001). Message framing may be an important
      factor to consider depending on the health benefit emphasised (disease symptom
      reduction or CVD risk reduction) and patient-stated priorities. Condition
      specific health messages in psoriasis populations may increase the likelihood of
      message effectiveness for alcohol reduction.

PMID- 29380627
TI  - The benefits of in silico modeling to identify possible small-molecule drugs and
      their off-target interactions.
AB  - The research into the use of small molecules as drugs continues to be a key
      driver in the development of molecular databases, computer-aided drug design
      software and collaborative platforms. The evolution of computational approaches
      is driven by the essential criteria that a drug molecule has to fulfill, from the
      affinity to targets to minimal side effects while having adequate absorption,
      distribution, metabolism, and excretion (ADME) properties. A combination of
      ligand- and structure-based drug development approaches is already used to obtain
      consensus predictions of small molecule activities and their off-target
      interactions. Further integration of these methods into easy-to-use workflows
      informed by systems biology could realize the full potential of available data in
      the drug discovery and reduce the attrition of drug candidates.

PMID- 29380628
TI  - Risk Factors for Failed Nonoperative Treatment and Rerupture in Acute Achilles
      Tendon Rupture.
AB  - BACKGROUND: Nonoperative treatment is feasible in most patients with acute
      Achilles tendon rupture. Risk factors associated with failed nonoperative
      treatment are poorly understood. We investigated risk factors associated with
      rerupture after nonoperative treatment and otherwise failed nonoperative
      treatment of Achilles tendon rupture. METHODS: All patients diagnosed with acute
      Achilles tendon rupture between January 2009 and June 2016 and who underwent 8
      weeks of nonoperative treatment with functional rehabilitation were included in
      the study. Patients with rerupture or otherwise failed nonoperative treatment
      were identified retrospectively. Time to rerupture and association of age, sex,
      time from injury, diabetes, and visits to the physiotherapist for cases of
      reruptures and otherwise failed nonoperative treatment were investigated. A total
      of 210 patients were included in the study. RESULTS: Fifteen patients sustained a
      rerupture. Rerupture incidence was 7.1%. Incidence of late reruptures, those
      occurring after return to daily activities at 12 weeks, was 1.9%. Six patients
      had otherwise failed nonoperative treatment. Median time to rerupture was 23 days
      (6 to 61) after the end of the treatment. The incidence of all-cause failure was
      10.0%. Male gender was associated with reruptures ( P = .013) and failed
      nonoperative treatment for any reason ( P = .029). CONCLUSION: It is important to
      highlight the increased risk of rerupture in male patients during the first month
      after the end of the nonoperative treatment. Age alone, even in male patients,
      was a poor indication for operative treatment since it did not predict early
      failure. Further studies will hopefully clarify the influence of activity level
      on the risk of rerupture. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 29380629
TI  - Cholinergic alterations by exposure to pesticides used in control vector: Guppies
      fish (Poecilia reticulta) as biological model.
AB  - Spinosad and temephos are two of the most used pesticides in Mexico for the
      control of vector causing disease such as dengue, chikungunya and Zika. The aim
      of this study was to compare the neurotoxic effects of these two pesticides using
      guppy fish (Poecilia reticulata) as a model organism. Guppies were exposed for 7
      and 21 days to technical grade temephos and spinosad at 1.0 and 0.07 g/L,
      respectively, (10 and 0.5 mg/L of active substance; concentrations recommended by
      the Ministery of Health of the State (Secretaria de Salud de Nayarit (SSN)
      Mexico)). Subsequently, acetylcholinesterase activity (AChE) and acetylcholine
      concentrations (ACh) in muscle tissue were determined. Temephos exposure
      decreased AChE activity and increased ACh concentration, whereas exposure to
      spinosad only increased ACh concentration. Though cholinergic alterations were
      more severe in fish exposed to temephos, both pesticides were equally lethal
      during the first seven days after exposure. Nonetheless, temephos was more lethal
      after 21 days.

PMID- 29380631
TI  - Corrigendum.

PMID- 29380630
TI  - ICRP Publication 137: Occupational Intakes of Radionuclides: Part 3.
AB  - Abstract -: The 2007 Recommendations of the International Commission on
      Radiological Protection (ICRP, 2007) introduced changes that affect the
      calculation of effective dose, and implied a revision of the dose coefficients
      for internal exposure, published previously in the Publication 30 series (ICRP,
      1979, 1980, 1981, 1988) and Publication 68 (ICRP, 1994). In addition, new data
      are now available that support an update of the radionuclide-specific information
      given in Publications 54 and 78 (ICRP, 1988a, 1997b) for the design of monitoring
      programmes and retrospective assessment of occupational internal doses. Provision
      of new biokinetic models, dose coefficients, monitoring methods, and bioassay
      data was performed by Committee 2, Task Group 21 on Internal Dosimetry, and Task
      Group 4 on Dose Calculations. A new series, the Occupational Intakes of
      Radionuclides (OIR) series, will replace the Publication 30 series and
      Publications 54, 68, and 78. OIR Part 1 has been issued (ICRP, 2015), and
      describes the assessment of internal occupational exposure to radionuclides,
      biokinetic and dosimetric models, methods of individual and workplace monitoring,
      and general aspects of retrospective dose assessment. OIR Part 2 (ICRP, 2016),
      this current publication and upcoming publications in the OIR series (Parts 4 and
      5) provide data on individual elements and their radioisotopes, including
      information on chemical forms encountered in the workplace; a list of principal
      radioisotopes and their physical half-lives and decay modes; the parameter values
      of the reference biokinetic model; and data on monitoring techniques for the
      radioisotopes encountered most commonly in workplaces. Reviews of data on
      inhalation, ingestion, and systemic biokinetics are also provided for most of the
      elements. Dosimetric data provided in the printed publications of the OIR series
      include tables of committed effective dose per intake (Sv Bq-1 intake) for
      inhalation and ingestion, tables of committed effective dose per content (Sv Bq-1
      measurement) for inhalation, and graphs of retention and excretion data per Bq
      intake for inhalation. These data are provided for all absorption types and for
      the most common isotope(s) of each element. The electronic annex that accompanies
      the OIR series of publications contains a comprehensive set of committed
      effective and equivalent dose coefficients, committed effective dose per content
      functions, and reference bioassay functions. Data are provided for inhalation,
      ingestion, and direct input to blood. This third publication in the series
      provides the above data for the following elements: ruthenium (Ru), antimony
      (Sb), tellurium (Te), iodine (I), caesium (Cs), barium (Ba), iridium (Ir), lead
      (Pb), bismuth (Bi), polonium (Po), radon (Rn), radium (Ra), thorium (Th), and
      uranium (U).

PMID- 29380633
TI  - Implementing a Produce Prescription Program for Hypertensive Patients in Safety
      Net Clinics.
AB  - INTRODUCTION: Although community-clinical linkages can improve chronic disease
      management, little is known regarding strategies for program implementation. We
      describe implementation of a unique produce prescription program for patients
      with hypertension (PRxHTN) involving 3 safety net clinics and 20 farmers' markets
      (FMs). STRATEGY: Safety net clinics were invited to participate, and provider
      leads received assistance in (1) developing a process flow to screen for food
      insecurity among hypertensive adults for program referral, (2) integrating the
      program into their electronic health record for scheduling, and (3) counseling
      patients on PRxHTN/FM use. Research staff met with clinics twice monthly. FM
      managers were trained on maintaining PRxHTN voucher redemption logs. DISCUSSION:
      A total of 7 diverse providers screened 266 patients over 3 months; 224 were
      enrolled. Twelve FM, including one newly established at a clinic through provider
      FM manager collaboration, redeemed over $14,500 of the $10 PRxHTN vouchers. We
      describe several strategies that can be used to prepare for and overcome
      implementation challenges including organizational and staff selection,
      facilitative administration, and clinical training and consultation. CONCLUSION:
      The PRxHTN program offers a flexible implementation process allowing clinics to
      successfully adapt their workflow to suit their staffing and resources.

PMID- 29380632
TI  - Model reduction methodology for computational simulations of endovascular repair.
AB  - Endovascular aneurysm repair (EVAR) is a current alternative treatment for
      thoracic and abdominal aortic aneurysms, but is still sometimes compromised by
      possible complications such as device migration or endoleaks. In order to assist
      clinicians in preventing these complications, finite element analysis (FEA) is a
      promising tool. However, the strong material and geometrical nonlinearities added
      to the complex multiple contacts result in costly finite-element models. To
      reduce this computational cost, we establish here an alternative and systematic
      methodology to simplify the computational simulations of stent-grafts (SG) based
      on FEA. The model reduction methodology relies on equivalent shell models with
      appropriate geometrical and mechanical parameters. It simplifies significantly
      the contact interactions but still shows very good agreement with a complete
      reference finite-element model. Finally, the computational time for EVAR
      simulations is reduced of a factor 6-10. An application is shown for the
      deployment of a SG during thoracic endovascular repair, showing that the
      developed methodology is both effective and accurate to determine the final
      position of the deployed SG inside the aneurysm.

PMID- 29380634
TI  - Trialing the Community-Based Collaborative Action Research Framework: Supporting
      Rural Health Through a Community Health Needs Assessment.
AB  - PURPOSE: To describe the application of the Community-Based Collaborative Action
      Research (CBCAR) framework to uplift rural community voices while conducting a
      community health needs assessment (CHNA) by formulating a partnership between a
      critical access hospital, public health agency, school of nursing, and community
      members to improve societal health of this rural community. METHOD: This
      prospective explorative study used the CBCAR framework in the design, collection,
      and analysis of the data. The framework phases include: Partnership, dialogue,
      pattern recognition, dialogue on meaning of pattern, insight into action, and
      reflecting on evolving pattern. DISCUSSION: Hospital and public health agency
      leaders learned how to use the CBCAR framework when conducting a CHNA to meet
      Affordable Care Act federal requirements. Closing the community engagement gap
      helped ensure all voices were heard, maximized intellectual capital, synergized
      efforts, improved communication by establishing trust, aligned resources with
      initiatives, and diminished power struggles regarding rural health. CONCLUSION:
      The CBCAR framework facilitated community engagement and promoted critical
      dialogue where community voices were heard. A sustainable community-based
      collaborative was formed. The project increased the critical access hospital's
      capacity to conduct a CHNA. The collaborative's decision-making capacity was
      challenged and ultimately strengthened as efforts continue to be made to address
      rural health.

PMID- 29380635
TI  - Recent advances on Toll-like receptor 4 modulation: new therapeutic perspectives.
AB  - Activation or inhibition of TLR4 by small molecules will provide in the next few
      years a new generation of therapeutics. TLR4 stimulation (agonism) by high
      affinity ligands mimicking lipid A gave vaccine adjuvants with improved
      specificity and efficacy that have been licensed and entered into the market.
      TLR4 inhibition (antagonism) prevents cytokine production at a very early stage;
      this is in principle a more efficient method to block inflammatory diseases
      compared to cytokines neutralization by antibodies. Advances in TLR4 modulation
      by drug-like small molecules achieved in the last years are reviewed. Recently
      discovered TLR4 agonists and antagonists of natural and synthetic origin are
      presented, and their mechanism of action and structure-activity relationship are
      discussed.

PMID- 29380636
TI  - Synthesis of novel quinine analogs and evaluation of their effects on Trypanosoma
      cruzi.
AB  - AIM: Chagas disease is a tropical disease caused by the hemoflagellate protozoan
      Trypanosoma cruzi. There is no vaccine for Chagas disease and available drugs
      (e.g., benznidazole) are effective only during the acute phase, displaying a
      variable curative activity in the established chronic form of the disease. New
      leads with high efficacy and better toxicity profiles are urgently required.
      Materials & methods: A library of novel quinine derivatives was synthesized using
      Heck chemistry and evaluated against the various developmental forms of T. cruzi.
      RESULTS AND CONCLUSION: Several novel quinine analogs with trypanocidal activity
      have been identified with the para-nitro-substituted derivative displaying a
      submicromolar IC50, which is 83-times lower than quinine and three-times lower
      than benznidazole. Transmission electron microscopy analysis demonstrated that
      these compounds induced a marked vacuolization of the kinetoplast of
      intracellular amastigotes and cell-derived trypomastigotes.

PMID- 29380637
TI  - Case Analysis of Factors Contributing to Patient Falls.
AB  - Falls are a constant risk for patients in acute-care hospitals, which can lead to
      serious consequences. The purpose of this study was to examine hospital fall case
      studies and to learn the contributing factors for patient falls. This was
      achieved by conducting a secondary analysis of 11 fall case studies obtained from
      two previous studies. The fall cases used the Senior Falls Investigative
      Methodology (SFIM) approach, which provided detailed analysis of the
      circumstances surrounding the falls. A total of 549 contributing factors were
      identified in the 11 case studies, where major categories were classified
      according to the four different layers of defenses using Reason's Swiss Cheese
      Model of Accident Causation (organizational factors, supervision, preconditions,
      and unsafe acts). Hospital policies, reduced supervision, disease processes, the
      environment, and patients transferring without assistance dominated the reasons
      for increased risk. Additional strategies were recommended for all layers of
      defense to reduce patient falls.

PMID- 29380638
TI  - Mental health and psychosocial characteristics of breast augmentation patients.
AB  - Cosmetic breast surgery experience and a wide range of mental health,
      psychosocial, and sociodemographic variables were assessed in the population
      based Norwegian Mother and Child Cohort Study ( N = 78,252). Breast augmentation
      patients reported elevated mental health problems. Factors in the domains of
      physical appearance, drug use, relationships, and exposure to abuse were all
      related to breast augmentation. Adjusting for such factors reduced the
      relationships between breast augmentation surgery and all mental health problems
      to non-significance. Results indicate that the increased prevalence of mental
      health problems among breast augmentation patients has to be understood from
      multiple perspectives involving several psychosocial domains.

PMID- 29380639
TI  - Novel applications for an established antimalarial drug: tumoricidal activity of
      quinacrine.
AB  - Quinacrine (QC), a synthetic antimalarial drug, was consistently used worldwide
      to combat malaria during the last century. Interestingly, later studies revealed
      that it also displays various additional properties, specifically antitumor
      activity. QC's antitumor activity occurs via a variety of pathways, including DNA
      intercalation, angiogenesis inhibition, signal transduction regulation, cell
      cycle arrest and autophagy induction. In combination with traditional therapies
      such as chemotherapy and radiotherapy, QC has also displayed synergistic effects
      against tumors, which may open promising therapeutic avenues. However, the
      breadth and complexity of its antitumor mechanisms have not yet been fully
      elucidated. In this review, we have systematically categorized QC's reported
      antitumor mechanisms from recent studies, to enable a deeper understanding of its
      antitumor activity.

PMID- 29380640
TI  - Associations between primary tumor RAS, BRAF and PIK3CA mutation status and
      metastatic site in patients with chemo-resistant metastatic colorectal cancer.
AB  - BACKGROUND: Several studies have investigated correlations between metastatic
      pattern and mutation status in patients with colorectal cancer (CRC). However,
      most of the studies were small and heterogeneously designed and further research
      is needed to confirm previous results. In this study, we investigated the
      association between RAS (KRAS or NRAS), BRAF, PIK3CA mutations and metastatic
      pattern in patients with metastatic (m) CRC. MATERIAL AND METHODS: This study
      reviewed Danish biobank and database of patients with mCRC who received cetuximab
      and irinotecan, independent of RAS mutation status, after fluoropyrimidine,
      oxaliplatin and irinotecan treatment failure. The database contained information
      regarding tumor mutation status of KRAS, NRAS, BRAF and PIK3CA genes. RESULTS:
      Totally, 448 patients were included. On multivariate analyses, RAS mutations were
      significantly associated with increased odds of having lung metastases at
      diagnosis of mCRC (odds ratio (OR) = 2.04; 95% confidence interval (CI) = 1.32
      3.17), and PIK3CA mutations with decreased odds of peritoneal metastases at
      diagnosis of mCRC (OR = 0.10; 95%CI = 0.01-0.79). On multivariate analyses of the
      hazard of developing metastases at any time during follow-up, RAS mutations were
      significantly associated with increased hazard of lung (hazard ratio (HR) = 1.34;
      95%CI = 1.04-1.72) and ovarian metastases (HR = 3.12; 95%CI = 1.05-9.24), BRAF
      V600E mutation was associated with increased hazard of skin metastases (HR =
      6.82; 95%CI = 1.86-25.02) and PIK3CA mutations with decreased hazard of
      peritoneal metastases (HR = 0.31; 95%CI = 0.11-0.86). CONCLUSIONS: This study
      indicated that in patients with mCRC, RAS mutations are associated with increased
      risk of lung and ovary metastases. BRAF V600E is associated with increased risk
      of skin metastases, and PIK3CA mutation with decreased risk of peritoneal
      metastases.

PMID- 29380641
TI  - Saccharomyces cerevisiae-based probiotic as novel anti-fungal and anti
      inflammatory agent for therapy of vaginal candidiasis.
AB  - Previously we demonstrated that the treatment with live Saccharomyces cerevisiae
      exerts beneficial therapeutic effects against vaginal candidiasis. Here, we
      address potential mechanisms particularly examining the probiotic capacity to
      modulate both fungus and host-related factors. We show that the S. cerevisiae
      based probiotic markedly affects the expression of virulence traits of Candida
      albicans such as aspartyl proteinases (SAPs) as well as hyphae-associated
      proteins Hwp1 and Ece1 in the vaginal cavity. On the host side, the probiotic
      suppression of the influx of neutrophils caused by the fungus into the vaginas of
      the mice is likely related to: (1) lower production of interleukin-8; and (2)
      inhibition of SAPs expression. However, these neutrophils displayed reactive
      oxygen species hyperproduction and increased killing activity as compared to the
      neutrophils of placebo-treated mice. There was no evidence of any cytotoxic
      effect by the probiotic, either when used in vivo on vaginal epithelial cell and
      organ architecture, or in in vitro in human vaginal epithelium. Inactivated yeast
      cells did not affect any of the factors above. In summary, the data suggest that
      the beneficial effect exerted by this S. cerevisiae-based probiotic is the result
      of its interference with the expression of fungus virulence factors coupled with
      the modulation of the inflammatory response of the host.

PMID- 29380642
TI  - Appropriate dose of Lactobacillus buchneri supplement improves intestinal
      microbiota and prevents diarrhoea in weaning Rex rabbits.
AB  - This study examined the effects on intestinal microbiota and diarrhoea of
      Lactobacillus buchneri supplementation to the diet of weaning Rex rabbits. To
      this end, rabbits were treated with L. buchneri at two different doses (LC: 104
      cfu/g diet and HC: 105 cfu/g diet) for 4 weeks. PCR-DGGE was used to determine
      the diversity of the intestinal microbiota, while real-time PCR permitted the
      detection of individual bacterial species. ELISA and real-time PCR allowed the
      identification of numerous cytokines in the intestinal tissues. Zonula occludens
      1, polymeric immunoglobulin receptor and immunoglobulin A genes were examined to
      evaluate intestinal barriers. Results showed that the biodiversity of the
      intestinal microbiota of weaning Rex rabbits improved in the whole tract of the
      treated groups. The abundance of most detected bacterial species was highly
      increased in the duodenum, jejunum and ileum after L. buchneri administration.
      The species abundance in the HC group was more increased than in the LC group
      when compared to the control. Although the abundance of Enterobacteriaceae
      exhibited a different pattern, Escherichia coli was inhibited in all treatment
      groups. Toll-like receptor (TLR)2 and TLR4 genes were down-regulated in all
      intestinal tissues as the microbiota changed. In the LC group, the secretion of
      the inflammatory cytokine tumour necrosis factor-alpha was reduced, the gene
      expression of the anti-inflammatory cytokine interleukin (IL)-4 was up-regulated
      and the expression of intestinal-barrier-related genes was enhanced. Conversely,
      IL-4 expression was increased and the expression of other tested genes did not
      change in the HC group. The beneficial effects of LC were greater than those of
      HC or the control in terms of improving the daily weight gain and survival rate
      of weaning Rex rabbits and reducing their diarrhoea rate. Therefore, 104 cfu/g L.
      buchneri treatment improved the microbiota of weaning Rex rabbits and prevented
      diarrhoea in these animals.

PMID- 29380643
TI  - Gut microbiota modulates type I interferon and antibody-mediated immune responses
      in chickens infected with influenza virus subtype H9N2.
AB  - Commensal gut microbes play a critical role in shaping host defences against
      pathogens, including influenza viruses. The current study was conducted to assess
      the role and mechanisms of action of commensal gut microbiota on the innate and
      antibody-mediated responses of layer chickens against influenza virus subtype
      H9N2. A total of 104 one-day-old specific pathogen free chickens were assigned to
      either of the four treatments, which included two levels of antibiotics treatment
      (ABX- and ABX+) and two levels of H9N2 virus infection (H9N2- and H9N2+). At day
      17 of age, chickens in the H9N2+ group were infected via the oral-nasal route
      with 400 MUl of 107 TCID50/ml (200 MUl/each route). Oropharyngeal and cloacal
      swabs at days 1, 3, 5, 7 and 9 post-infection (p.i.) for virus shedding, tissue
      samples at 12 h, 24 h and 36 h p.i. for mRNA measurement, and serum samples at
      days 7 and 14 p.i. for hemagglutination inhibition (HI) assay and IgG antibodies
      were collected. Virus shedding analysis showed that antibiotic treated (depleted)
      H9N2 virus infected chickens showed a significantly higher oropharyngeal virus
      shedding at all time points, and cloacal shedding at days 3 and 5 p.i. compared
      to control treated (undepleted)-H9N2 infected chickens. Analysis of mRNA
      expression showed that infection of depleted chickens with H9N2 virus resulted in
      significantly down-regulated type I interferon responses both in the respiratory
      and gastrointestinal tracts compared to undepleted-H9N2 infected chickens.
      However, antibody-mediated immune response analysis showed a significantly higher
      HI antibody titre and IgG levels in the serum of chickens depleted with
      antibiotics and infected with H9N2 virus compared to undepleted-H9N2 infected
      chickens. In conclusion, findings from the current study suggest that the gut
      microbiota of chickens plays an important role in the initiation of innate
      responses against influenza virus infection, while the antibody-mediated immune
      response remains unaffected.

PMID- 29380644
TI  - Impact of beneficial bacteria supplementation on the gut microbiota, colony
      development and productivity of Apis mellifera L.
AB  - Honey bees are important pollinators of several crops and ecosystems, having a
      great ecological and economic value. In Europe, the restricted use of chemicals
      and therapeutic agents in the beekeeping sector has stimulated the search for
      natural alternatives with a special focus on gut symbionts. The modulation of the
      gut microbiota has been recognised as a practical and successful approach in the
      entomological field for the management of insect-related problems. To date, only
      a few studies have investigated the effect of bacterial supplementation on the
      health status of colonies, colony productivity and gut symbionts. To this
      purpose, a preparation of sugar syrup containing bifidobacteria and lactobacilli
      isolated from bee gut was sprayed on the frames of an apiary located in open
      field once a week for four weeks. Treated and control hives were monitored for
      two months for brood extension, honey and pollen harvest. The presence of
      beneficial gut microorganisms within bee gut was investigated with denaturing
      gradient gel electrophoresis and next generation sequencing. The administered
      bacteria led to a significant increase of brood population (46.2%), pollen
      (53.4%) and harvestable honey in honey supers (59.21%). Analysis of the gut
      microbiota on the new generation of bees in treated hives showed an increase in
      relative abundance of Acetobacteraceae and Bifidobacterium spp., which are known
      to be involved in bee nutrition and protection.

PMID- 29380646
TI  - A simple risk score based on sleep quality for predicting depressive symptoms in
      menopausal women: a multicenter study.
AB  - OBJECTIVE: We aim to establish a simple risk score based on sleep quality for
      predicting depressive symptoms in menopausal women through a cross-sectional
      investigation. MATERIALS AND METHODS: A total of 705 Chinese women aged 40-60
      years were included in this cross-sectional investigation of a self-report
      questionnaire from the Physical Examination Center at Shanghai Jiao Tong
      University Affiliated Sixth People's Hospital. Depressive symptoms and sleep
      quality were evaluated using self-rating depressive symptom scale (SDS)and the
      Pittsburgh Sleep Quality Index (PSQI), respectively. After setting up a logistic
      regression model and computing the odds ratio value, we further calculated and
      predicted the risk score for depressive symptoms and then established a risk
      score system. Finally, we validated the risk score in two investigations
      (Validation 1 and Validation 2). RESULTS: The risk scoring system for predicting
      depressive symptoms included a history of cancer, subjective sleep quality, sleep
      disorder and daytime dysfunction, with total scores ranging from 0-35 points. The
      receiver operating characteristic (ROC) sample curve was 0.801 (95% CI 0.753
      0.848). The Area Under the Curve (AUC) was 0.832 (95% CI 0.738-0.925) in
      Validation 1 and 0.799 (95%CI 0.667-0.930) in Validation 2. The best cutoff point
      for depressive symptoms in the sample population was >=8 points, and the
      sensitivity and specificity were 0.698 and 0.824, respectively. The sensitivity
      was 0.775 and 0.667 in Validation 1 and Validation 2, respectively. CONCLUSIONS:
      The risk score for predicting depressive symptoms in menopausal women based on
      sleep is convenient. Because there is no complex assessment of multiple scales
      requiredIt may be a preliminary screening tool for depressive symptoms in
      menopausal women.

PMID- 29380645
TI  - Variations in diet cause alterations in microbiota and metabolites that follow
      changes in disease severity in a multiple sclerosis model.
AB  - Multiple sclerosis (MS) is a metabolically demanding disease involving immune
      mediated destruction of myelin in the central nervous system. We previously
      demonstrated a significant alteration in disease course in the experimental
      autoimmune encephalomyelitis (EAE) preclinical model of MS due to diet. Based on
      the established crosstalk between metabolism and gut microbiota, we took an
      unbiased sampling of microbiota, in the stool, and metabolites, in the serum and
      stool, from mice (Mus musculus) on the two different diets, the Teklad global soy
      protein-free extruded rodent diet (irradiated diet) and the Teklad sterilisable
      rodent diet (autoclaved diet). Within the microbiota, the genus Lactobacillus was
      found to be inversely correlated with EAE severity. Therapeutic treatment with
      Lactobacillus paracasei resulted in a significant reduction in the incidence of
      disease, clinical scores and the amount of weight loss in EAE mice. Within the
      metabolites, we identified shifts in glycolysis and the tricarboxylic acid cycle
      that may explain the differences in disease severity between the different diets
      in EAE. This work begins to elucidate the relationship between diet, microbiota
      and metabolism in the EAE preclinical model of MS and identifies targets for
      further study with the goal to more specifically probe the complex metabolic
      interaction at play in EAE that may have translational relevance to MS patients.

PMID- 29380647
TI  - Antifungal activity of clinical Lactobacillus strains against Candida albicans
      biofilms: identification of potential probiotic candidates to prevent oral
      candidiasis.
AB  - This study isolated Lactobacillus strains from caries-free subjects and evaluated
      the inhibitory effects directly on three strains of C. albicans, two clinical
      strains and one reference strain. Thirty Lactobacillus strains were isolated and
      evaluated for antimicrobial activity against in vitro C. albicans biofilms. L.
      paracasei 28.4, L. rhamnosus 5.2 and L. fermentum 20.4 isolates exhibited the
      most significant inhibitory activity against C. albicans. Co-incubation between
      these microorganisms resulted in deterrence of biofilm development and
      retardation of hyphal formation. The hindrance of biofilm development was
      characterized by the downregulated expression of C. albicans biofilm-specific
      genes (ALS3, HWP1, EFG1 and CPH1). L. paracasei 28.4, L. rhamnosus 5.2 and L.
      fermentum 20.4 demonstrated the ability to exert antifungal activity through the
      inhibition of C. albicans biofilms.

PMID- 29380648
TI  - Fort da: Fancy words for a patient's fuck you or exploring subject permanence in
      the therapeutic clinical encounter.

PMID- 29380649
TI  - Characterizing the good-enough Balint group: A work in progress.

PMID- 29380650
TI  - Demystifying Balint culture and its impact: An autoethnographic analysis.
AB  - Balint groups are a structured group process designed for physicians and other
      helping professionals to provide feedback to each other concerning troublesome
      patient encounters. The process of Balint groups has survived and even thrived
      for more than a half century since their inception, suggesting their inherent
      value. However, measuring the impact in order to communicate the nature of that
      value has been elusive. A recent literature review highlighted the equivocal
      nature of research results and suggested that well-designed qualitative research
      may be more effective in selecting target measures which could result in better
      evidence for this group process. This paper describes such an effort using a
      qualitative analysis of the author's own reflections about significant moments
      and learnings while participating in Balint groups.

PMID- 29380651
TI  - Non-Decaying postsynaptics potentials and delayed spikes in hippocampal pyramidal
      neurons generated by a zero slope conductance created by the persistent Na+
      current.
AB  - The negative slope conductance created by the persistent sodium current (INaP)
      prolongs the decay phase of excitatory postsynaptic potentials (EPSPs). In a
      recent study, we demonstrated that this effect was due to an increase of the
      membrane time constant. When the negative slope conductance opposes completely
      the positive slope conductances of the other currents it creates a zero slope
      conductance region. In this region the membrane time constant is infinite and the
      decay phase of the EPSPs is virtually absent. Here we show that non-decaying
      EPSPs are present in CA1 hippocampal pyramidal cells in the zero slope
      conductance region, in the suprathreshold range of membrane potential. Na+
      channel block with tetrodotoxin abolishes the non-decaying EPSPs. Interestingly,
      the non-decaying EPSPs are observed only in response to artificial excitatory
      postsynaptic currents (aEPSCs) of small amplitude, and not in response to aEPSCs
      of big amplitude. We also observed concomitantly delayed spikes with long
      latencies and high variability only in response to small amplitude aEPSCs. Our
      results showed that in CA1 pyramidal neurons INaP creates non-decaying EPSPs and
      delayed spikes in the subthreshold range of membrane potentials, which could
      potentiate synaptic integration of synaptic potentials coming from distal regions
      of the dendritic tree.

PMID- 29380652
TI  - Shifting Perceptions of Consequences of IPV Among Beneficiaries of Indashyikirwa:
      An IPV Prevention Program in Rwanda.
AB  - Indashyikirwa is a Rwandan program that seeks to prevent intimate partner
      violence (IPV) and support healthy, equitable relationships. A fundamental
      program aspect is a 5-month curriculum among heterosexual couples designed to
      identify the causes and consequences of economic, emotional, physical, and sexual
      IPV, and build skills to manage triggers of IPV. The program also trained opinion
      leaders to more effectively prevent and respond to IPV, and established women's
      safe spaces to educate women about their rights, refer or accompany women who
      wish to report abuse or seek services. Drawing on 30 interviews with couples and
      9 interviews with opinion leaders before and after completing the Indashyikirwa
      trainings, this article highlights beneficiaries' perceived consequences of IPV,
      and how such perceptions were influenced through the Indashyikirwa program.
      Interviews were conducted in Kinyarwanda, recorded, translated, and transcribed
      into English and analyzed thematically. The data reveal a depth of understanding
      of consequences of various forms of IPV. Although several participants justified
      more minor forms of men's physical IPV, such as slapping, severe consequences of
      physical IPV were most readily identified and sanctioned. Various harms of
      emotional and economic IPV were reported, yet these forms of IPV were typically
      less socially sanctioned or identified as IPV. Conceptions of sexual IPV were
      influenced by inequitable gender norms, and not typically recognized as a
      violation under the law. Although the data do not yet demonstrate the long-term
      impact, collectively identifying the overlapping consequences and underlying
      power inequalities for all forms of IPV, the legal rights protecting against
      various forms of IPV, and the benefits of nonviolent, equitable relationships,
      appeared to be helpful to shift perceptions of consequences of IPV. Implications
      of the findings for the program and broader IPV prevention are identified.

PMID- 29380653
TI  - Psychopathic Traits and Sexual Coercion Against Relationship Partners in Men and
      Women.
AB  - The present study examined the relationships between psychopathic traits, gender,
      and sexual coercion perpetration in the specific context of intimate partner
      relationships. Community-dwelling adult men and women with recent criminal or
      substance-use histories ( N = 300) completed self-report measures of psychopathic
      personality traits (interpersonal, affective, lifestyle, and antisocial facets),
      sexual coercion perpetrated within their most recent relationship, and other
      relevant behaviors including physical intimate partner violence perpetration and
      sexual coercion victimization. Results of regression analyses showed that the
      relationship between psychopathic trait facets and sexual coercion was moderated
      by gender, with effects varying based on level of coercion severity.
      Specifically, women who showed high levels of interpersonal psychopathic traits
      (superficial charm, social dominance) were more likely to engage in any sexual
      coercion and minor severity sexual coercion than women with low levels of
      interpersonal traits. For severe coercion, women who showed low levels of
      affective psychopathic traits (coldness, lack of empathy) or high levels of
      antisocial psychopathic traits (aggressiveness, criminality) were more likely to
      be sexually coercive than other women. Relationships between the four
      psychopathic trait facets and sexual coercion were more modest and nonsignificant
      for men at any level of coercion severity. Results are discussed in the context
      of sociocultural factors that may influence the role of psychopathic traits on
      sexual coercion as a function of gender and relationship contexts, including
      traditional sexual scripts, the cultural role of women as sexual gatekeepers, and
      beliefs about token resistance.

PMID- 29380654
TI  - How is internal migration reshaping metropolitan populations in Latin America? A
      new method and new evidence.
AB  - Internal migration is a key driver of patterns of human settlement and socio
      economic development, but little is known about its compositional impacts.
      Exploiting the wide availability of census data, we propose a method to quantify
      the internal migration impacts on local population structures, and estimate these
      impacts for eight large Latin American cities. We show that internal migration
      generally had small feminizing, downgrading educational, and demographic window
      effects: reducing the local sex ratio, lowering the average years of schooling,
      and raising the share of working-age population due to an increased young adult
      population. Over time, a rise in the proportion of males and a drop in the share
      of the young adult population moving into cities reduced the feminizing and
      demographic window effects. Concurrently, a rise in the average years of
      schooling associated with people moving into cities attenuated the downgrading
      impact of internal migration on local education levels.

PMID- 29380655
TI  - Status of Endovascular Aneurysm Sealing After 5 Years of Commercial Use.
AB  - Endovascular aneurysm sealing (EVAS) using the Nellix Endovascular Sealing System
      was introduced commercially in 2013 with the aim of reducing the incidences of
      reintervention and late complications observed after conventional endovascular
      aneurysm repair (EVAR). In the 5 years since its commercial launch, the Nellix
      system has evolved in terms of its structure, instructions for use, and delivery
      technique. Complications, including migration and proximal endoleak, have been
      recognized and treatment strategies developed, although durability remains to be
      demonstrated. Prospective multicenter trials have shown a low incidence of type I
      endoleak and reintervention at 1-year follow-up, comparable to conventional EVAR
      with modern devices. Since the aneurysm sac is "actively managed" with EVAS,
      similar to open surgical repair, type II endoleaks are rare with the Nellix
      system. Unexpected benefits of active sac management with EVAS include reduced
      incidences of postimplantation syndrome and cardiac complications, with low all
      cause mortality at 1 year. Less neck dilatation compared to EVAR has also been
      observed. The Nellix device and procedure continue to evolve, and further
      prospective studies are indicated. This article analyzes the current EVAS
      evidence to update our knowledge of this technique in the management of abdominal
      aortic aneurysm.

PMID- 29380656
TI  - Comparing time-based and event-based prospective memory over short delays.
AB  - The current study compared monitoring in time- and event-based prospective memory
      (PM). Time- and event-based non-focal task instructions were given after a
      baseline block of a lexical decision ongoing task. Delay between instruction and
      presentation of PM cue/time was manipulated between-subjects to examine
      monitoring across short delays (1-6 min). Longer delays decreased performance in
      the event-based task, but not in the time-based task. This accuracy decline was
      accompanied by a decline in monitoring (as measured by PM cost to the ongoing
      task in the trials immediately before the PM cue was presented) between the 1 and
      3 min delays. Monitoring was only evident for the time-based task at the 6 min
      delay as measured by PM cost to the ongoing task. Clock checks were also not
      affected by delay, but did increase in frequency as the response time neared.
      These results suggest that delay from the time of intention formation decreases
      both accuracy and monitoring in event-based tasks, but does not decrease accuracy
      or monitoring in time-based tasks.

PMID- 29380658
TI  - Mothers' Grief Experiences of Losing Their Only Child in the 2008 Sichuan
      Earthquake: A Qualitative Longitudinal Study.
AB  - The purpose of this study is to explore bereaved mothers' 2-year experiences of
      losing their only child in the 2008 Sichuan earthquake. Taking an interpretative
      phenomenological approach, this study interviewed six bereaved mothers four times
      (6 months, 12 months, 18 months, and 24 months) in Dujiangyan area in Sichuan
      Province. The findings suggest that these mothers' personal grief experiences
      evolved: initially, anger toward the cause of their children's deaths, following
      despair of meaningless life, guilt and regret, and finally yearning. Although
      their yearning and missing ebbed after 2 years, these mothers still had
      unresolved grief. These mothers also faced strained marital relationships and
      additional pressure from social interactions. This study illuminates that these
      mothers' personal grief experiences and their coping strategies corresponded to
      Chinese family and sociocultural context.

PMID- 29380657
TI  - Long-Term maintenance of anomia treatment effects in primary progressive aphasia.
AB  - This study examined the maintenance of anomia treatment effects in primary
      progressive aphasia (PPA). Following baseline testing, a phonological treatment
      and an orthographic treatment were administered over the course of six months.
      The treatment stimuli consisted of nouns that were consistently named correctly
      at baseline (Prophylaxis items) and/or nouns that were consistently named
      incorrectly at baseline (Remediation items). Naming accuracy was measured at
      baseline, and it was measured at 1 month, 8 months, and 15 months post-treatment.
      The change in naming accuracy from baseline to each post-treatment evaluation was
      calculated within each treatment condition, and within a matched untrained
      condition. The change in naming accuracy was then compared between the three
      conditions. The results of these analyses indicate that phonological and
      orthographic treatments are both effective in the Prophylaxis and Remediation of
      anomia in all three variants of PPA. For Prophylaxis items, some of the effects
      of each treatment can persist for as long as 15 months post-treatment. These long
      term treatment effects were more robust in the orthographic treatment condition
      and for participants with the semantic variant of PPA.

PMID- 29380659
TI  - The Impact on Mental Health of Losing an Only Child and the Influence of Social
      Support and Resilience.
AB  - The number of parents who have lost their only child (PLOCs) has increased
      annually with the implementation of the birth control policy in mainland China.
      This study aimed to investigate the mental health status of PLOCs and the
      influence of social support and resilience. Study 1 recruited 100 PLOCs and 88
      nonbereaved parents, and compared differences in depression, anxiety, and
      loneliness. Study 2 investigated the influence of social support and resilience
      on the mental health of PLOCs via a mediating model. Results indicate that PLOCs
      reported more anxiety and depression symptoms than nonbereaved counterparts.
      Perceived close family support, objective support, and resilience negatively
      predicted anxiety and depression. In addition, perceived close family support was
      found to influence mental health via resilience. The current findings reveal that
      losing an only child has long-term negative impacts on the mental health of
      PLOCs. However, perceived close family support and objective support can protect
      their mental health either directly or indirectly via resilience.

PMID- 29380660
TI  - Validity of Brief Cognitive Assessment Tool modifications for older adults with
      visual and motor limitations.
AB  - INTRODUCTION: The prevalence of cognitive, sensory, and physical impairments is
      expected to grow alongside increasing life expectancy. These chronic conditions
      pose challenges for geriatric assessment. We examined whether Brief Cognitive
      Assessment Tool (BCAT) modifications to accommodate visual and motor limitations
      would retain strong validity for identifying mild cognitive impairment (MCI) and
      dementia. METHOD: Psychometric analyses were performed on archival data (N = 458)
      from community-dwelling older adults and residents of assisted living facilities
      and nursing homes in Maryland, USA (age >= 50 years). Participants completed a
      brief testing battery, including the BCAT, and were assigned a cognitive
      diagnosis (normal cognition, MCI, mild dementia, moderate dementia, severe
      dementia) by licensed clinical psychologists. RESULTS: Receiver operator
      characteristic curve analyses evidenced excellent diagnostic validity of BCAT
      modification cutoffs for identifying the cognitive categories. Contextual memory
      and executive control factors, which explained over 80% of variance in cognitive
      diagnoses, may account for the preservation of validity despite BCAT
      modifications. CONCLUSIONS: The results indicate strong psychometric evidence for
      the BCAT modifications and provide cutoffs for identifying MCI and staging
      dementia. For clinicians, the score guidelines are preferable to the guesswork
      involved with adjusting cutoffs to accommodate visual and motor limitations.

PMID- 29380661
TI  - Evaluation of wound healing effect of alginate films containin g Aloe vera ( Aloe
      barbadensis Miller) gel.
AB  - A new alginate dressing with Aloe vera gel was developed and used to study its
      cutaneous healing effect in vivo by surgical wounds in Wistar rats. The aloe
      alginate film was characterized by Fourier-transform infrared spectroscopy,
      mechanical properties, scanning electron microscopy, hydration rate, and calcium
      release. The aloe-alginate film demonstrated desirable physical and mechanical
      characteristics for wound dressing application. The animals were divided in three
      groups (n = 20): gauze bandage, alginate film, and aloe-alginate film. The
      histological analysis on the 3rd, 7th, 14th, and 22nd days after the treatment
      showed that the aloe-alginate films modulated the inflammatory phase and
      decreased the quantity of macrophages when compared to the alginate film group
      and the control (gauze bandage). The evaluation of collagen fibers showed a
      decrease in type III and increase in type I fibers on group treated with aloe
      alginate film suggesting an improvement in the progression of the healing
      process.

PMID- 29380662
TI  - Vancomycin-impregnated electrospun polycaprolactone (PCL) membrane for the
      treatment of infected bone defects: An animal study.
AB  - There is no consensus for the management of critical infected bone defects. The
      purpose of this study was to produce a vancomycin-impregnated electrospun
      polycaprolactone (PCL) membrane for the treatment of infected critical bone
      defects, and test it in a rabbit model. Electrospinning produced a resorbable PCL
      fiber membrane containing vancomycin approximately 1 mm in thickness, with a pore
      diameter of <10 MUm. Femur defects were made in the limbs of 18 rabbits and
      infected with Staphylococcus aureus. The rabbits were divided into three groups
      according to treatment: (1) Experimental group: rabbit freeze-dried allogeneic
      bone graft and the vancomycin-PCL membrane. (2) Control group 1: bone graft. (3)
      Control group 2: vancomycin-PCL membrane only. Culture showed no difference in
      osteoclast activity between the three groups. Transwell testing showed that
      almost no fibroblasts passed through the membrane during the first 24 h, but some
      fibroblasts were able to pass it after 72 h. At 12 weeks after surgery, there was
      significantly less inflammatory cell infiltration in the experimental compared to
      the control groups. New bone formation and fracture bone callus were greater in
      the experimental group than control groups. We thus conclude the resorbable
      electrospun vancomycin-impregnated PCL membrane was effective at controlling bone
      infection, and in the regeneration of bone in a critical bone defect animal
      model.

PMID- 29380664
TI  - Wernicke-Korsakoff syndrome as a rare phenotype of sporadic Creutzfeldt-Jakob
      disease.
AB  - We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an
      early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66
      year-old female complained of dizziness and imbalance which mostly occurred while
      walking. A neurological examination revealed a triad of symptoms characteristic
      for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory
      disturbances with confabulations. The disturbances increased during the course of
      the disease, which led to the death of the patient four months after the
      appearance of the signs. The patient was finally diagnosed with sCJD disease. The
      most useful ancillary examination results supporting sCJD diagnosis were brain
      diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the
      presence of 14-3-3 protein in CSF (cerebrospinal fluid). Since that manifestation
      of sCJD is very unique other causes should be taken into consideration while
      making a final diagnosis.

PMID- 29380665
TI  - Repeated cocaine exposure dysregulates BDNF expression and signaling in the
      mesocorticolimbic pathway of the adolescent rat.
AB  - OBJECTIVES: Long-term abstinence following cocaine exposure up-regulates brain
      derived neurotrophic factor (BDNF) expression in the mesocorticolimbic pathway.
      Given the increased vulnerability to drug abuse typical of adolescence, we
      hypothesized that changes in BDNF expression may become manifest early after the
      end of cocaine treatment in the adolescent brain. METHODS: Rats received cocaine
      injections from postnatal day 28 (PND28) to PND42 and the mesocorticolimbic
      expression of BDNF was measured by real-time PCR and Western blotting at PND43.
      RESULTS: In the ventral tegmental area, BDNF-tropomyosin receptor kinase B
      (TrKappaB) expression and phosphorylation are enhanced while the intracellular
      signaling is unaltered. In the nucleus accumbens (NAc) shell and core, BDNF and
      its signaling were down-regulated. In the prelimbic (PL) cortex, we found reduced
      BDNF expression and increased phosphoprylation of TrKappaB, ERK and AKT. In the
      infralimbic (IL) cortex, increased BDNF expression was coupled with reduced
      activity and expression of its downstream targets. To evaluate the role of
      glutamate on BDNF-independent changes, we investigated the expression of the
      transporter GLT-1 and the activation of the NMDA receptor subunit GluN2B, which
      were both increased in the PL cortex while reduced in the IL cortex. CONCLUSIONS:
      Our results show that adolescent cocaine exposure modulates BDNF system early
      after treatment in the mesocorticolimbic pathway, identifying a complex but
      specific set of changes that could provide clues for treatment.

PMID- 29380666
TI  - The health choices book: Learning to think carefully about treatments The health
      choices book: Learning to think carefully about treatments. A health science book
      for primary school children.

PMID- 29380667
TI  - Skin Diseases in the Era of Highly Active Antiretroviral Therapy: A Retrospective
      Study of 534 Patients.
AB  - BACKGROUND: With the increasing number of HIV-infected patients receiving highly
      active antiretroviral therapy (HAART), the shift in their dermatologic profile
      becomes less characteristic of AIDS-defining illnesses. METHODS: Retrospective
      review of mucocutaneous pathology among patients seen at HIV-Dermatology Clinic
      from January 2009 to December 2013. RESULTS: Among 534 patients, there were 68.4%
      males and 31.6% females, with 8.7-year average duration of infection; 82.8% were
      receiving HAART. Kaposi sarcoma was the only relatively frequent AIDS-defining
      disease. Fungal and viral infections were common, with human papilloma virus
      (HPV) as the most frequent overall. Benign and premalignant tumors were
      associated with HAART and CD4 >200/mm3 ( P < .05). Psoriasis was prevalent among
      patients without HAART ( P < .05). Prurigo was associated with lower CD4 count (
      P < .001). CONCLUSION: Patients receiving HAART are faced with chronic skin
      problems such as benign and premalignant tumors, and HPV infection adds to their
      neoplastic predisposition. Further research is recommended to develop protocols
      for treating psoriasis and screening for HPV-associated neoplasia among patients.

PMID- 29380668
TI  - Whether Patients Want It or Not, Physician Recommendations Will Convince Them to
      Accept HIV Testing.
AB  - Physicians are not routinely offering patients HIV testing, partly due to
      perceived patient discomfort with discussing HIV. This study assessed patients'
      comfort level and whether physician recommendations can overcome any discomfort
      that does exist. In a publicly funded primary care clinic, we administered a
      survey exploring patient facilitators to HIV testing, with 266 patients answering
      the 2 main survey questions of interest. Most participants wanted their physician
      to offer HIV testing (n = 175; 65.8%). Even among participants who did not want
      their physician to offer HIV testing (n = 91), over half (n = 54; 59.3%) reported
      they would "likely" or "very likely" accept HIV testing if their physician
      recommended it. Based on our findings, not only are negative attitudes about HIV
      testing among patients uncommon but physician recommendations may be able to
      convince patients to receive HIV testing in spite of patients stating they do not
      want the test.

PMID- 29380669
TI  - Cerebral blood flow measured by positron emission tomography during normothermic
      cardiopulmonary bypass: an experimental porcine study.
AB  - BACKGROUND: Mean arterial blood pressure (MAP) and/or pump flow during
      normothermic cardiopulmonary bypass (CPB) are the most important factors of
      cerebral perfusion. The aim of this study was to explore the influence of CPB
      blood flow on cerebral blood flow (CBF) measured by dynamic positron emission
      tomography (PET) using 15O-labelled water with no pharmacological interventions
      to maintain the MAP. METHODS: Eight pigs (69-71 kg) were connected to
      normothermic CPB. After 60 minutes (min) with a CPB pump flow of 60 mL/kg/min,
      the pigs were changed to either 35 mL/kg/min or 47.5 mL/kg/min for 60 min and,
      thereafter, all the pigs returned to 60 mL/kg/min for another 60 min. The MAP was
      measured continuously and the CBF was measured by positron emission tomography
      (PET) during spontaneous circulation and at each CPB pump flow after 30 min of
      steady state. RESULTS: Two pigs were excluded due to complications. CBF increased
      from spontaneous circulation to a CPB pump flow of 60 mL/kg/min. A reduction in
      CPB pump flow to 47.5 mL/kg/min (n=3) resulted in only minor changes in CBF while
      a reduction to 35 mL/kg/min (n=3) caused a pronounced change (correlation
      coefficient (R2) 0.56). A return of CPB pump flow to 60 mL/kg/min was followed by
      an increase in CBF, except in the one pig with the lowest CBF during low flow
      (R2=0.44). CBF and MAP were not correlated (R2=0.20). CONCLUSION: In this
      experimental porcine study, a relationship was observed between pump flow and CBF
      under normothermic low-flow CPB. The effect of low pump flow on MAP showed
      substantial variations, with no correlation between CBF and MAP.

PMID- 29380670
TI  - A type 6 secretion system (T6SS) encoded gene within Salmonella enterica serovar
      Enteritidis contributes to virulence.
AB  - Bacteria interact with their host through protein secretion systems and surface
      structures. Pathogenic bacteria encode protein secretion systems that promote the
      invasion of the host's tissue, the evasion of the host's immune response, the
      thwarting microbial competitors, and ultimately survival within the host. For
      motile bacteria, the presence of extracellular flagella provides the host with a
      structural motif used for activation of the immune system. Within this issue of
      Virulence, the article "Identification of a novel gene in ROD9 island of
      Salmonella Enteritidis involved in the alteration of virulence-associated protein
      expression" describes the contribution of a gene, SEN1005, toward host-pathogen
      interaction. The authors demonstrate the contribution of SEN1005 to cell culture
      bioassays and infection in a mouse model of colitis. In each tested scenario,
      deletion of SEN1005 results in a phenotypic defect that was complemented by
      providing the SEN1005 gene in trans. SEN1005 contributes to the expression of
      known virulence factors within SPI-1, flagellar and chemotaxis genes, and heat
      shock/chaperone genes. Although much work is needed to fully elucidate the
      function of SEN1005, this work contributes toward our understanding of the
      genetic factors used by Salmonella to cause foodborne illnesses.

PMID- 29380671
TI  - SSTR2 associated with neuronal apoptosis after intracerebral hemorrhage in adult
      rats.
AB  - Objective SSTR2 is a member of superfamily of SST receptor (SSTR), and widely
      expressed in the brain; however, the knowledge of its functions in area adjacent
      to hematoma after intracerebral hemorrhage (ICH) is still limited. Method The
      role of SSTR2 in the processes of ICH was explored by conducting an ICH rat
      model. Western blot and immunohistochemistry were employed to examine the level
      of SSTR2 in area adjacent to hematoma after ICH. Immunofluorescent staining was
      used to observe the spatial correlation of SSTR2 with cellular types adjacent to
      hematoma after ICH. RNA interference specific to SSTR2 was adopted in PC12 cells
      to clarify the causal correlation between SSTR2 and neuronal activities. Results
      Increased expression of SSTR2 was observed and restricted to the neurons adjacent
      to hematoma following ICH. Immunofluorescent staining showed that SSTR2 was
      significant increased in neurons, but not astrocytes or microglia. Increasing
      SSTR2 level was found to be accompanied by the up-regulation of activated caspase
      3 and the down-expression of p-Akt in a time-dependent manner. What's more, using
      SSTR2 RNA interference (SSTR2-RNAi) in PC12 cells, we indicated that SSTR2 might
      have a pro-apoptotic role in neurons. Conclusion We speculated that SSTR2 might
      exert its pro-apoptotic function in neurons through inhibiting Akt activity
      following ICH.

PMID- 29380672
TI  - Hierarchical virtual screening of the dual MMP-2/HDAC-6 inhibitors from natural
      products based on pharmacophore models and molecular docking.
AB  - The dual-target inhibitors tend to improve the response rate in treating tumors,
      comparing with the single-target inhibitors. Matrix metalloproteinase-2 (MMP-2)
      and histone deacetylase-6 (HDAC-6) are attractive targets for cancer therapy. In
      this study, the hierarchical virtual screening of dual MMP-2/HDAC-6 inhibitors
      from natural products is investigated. The pharmacophore model of MMP-2
      inhibitors is built based on ligands, but the pharmacophore model of HDAC-6
      inhibitors is built based on the experimental crystal structures of multiple
      receptor-ligand complexes. The reliability of these two pharmacophore models is
      validated subsequently. The hierarchical virtual screening, combining these two
      different pharmacophore models of MMP-2 and HDAC-6 inhibitors with molecular
      docking, is carried out to identify the dual MMP-2/HDAC-6 inhibitors from a
      database of natural products. The four potential dual MMP-2/HDAC-6 inhibitors of
      natural products, STOCK1 N-46177, STOCK1 N-52245, STOCK1 N-55477, and STOCK1 N
      69706, are found. The studies of binding modes show that the screened four
      natural products can simultaneously well bind with the MMP-2 and HDAC-6 active
      sites by different kinds of interactions, to inhibit the MMP-2 and HDAC-6
      activities. In addition, the ADMET properties of screened four natural products
      are assessed. These found dual MMP-2/HDAC-6 inhibitors of natural products could
      serve as the lead compounds for designing the new dual MMP-2/HDAC-6 inhibitors
      having higher biological activities by carrying out structural modifications and
      optimizations in the future studies.

PMID- 29380673
TI  - The new watchdogs' vision of science: A roundtable with Ivan Oransky ( Retraction
      Watch) and Brandon Stell ( PubPeer).
AB  - On March 3rd, 2016, the authors of this note hosted a conference entitled
      'Destabilized Science' at the University of California, Los Angeles, to which we
      invited two representatives of core actors within the new science watchdog pack:
      Ivan Oransky, co-founder in 2010 of Retraction Watch, and Brandon Stell, co
      founder in 2012 of PubPeer. After the formal conference, we organized a
      roundtable to discuss these invitees' experience and their vision of contemporary
      science. Mario Biagioli (University of California, Davis), Michael Chwe (UCLA)
      and Aaron Panofsky (UCLA) participated to the conversation. An edited transcript
      of the discussion and a short podcast version are being published on
      Transmissions ( ssstransmissions.org ) the new blog associated with Social
      Studies of Science.

PMID- 29380674
TI  - Identification of the hot spot residues for pyridine derivative inhibitor
      CCT251455 and ATP substrate binding on monopolar spindle 1 (MPS1) kinase by
      molecular dynamic simulation.
AB  - Protein kinase monopolar spindle 1 plays an important role in spindle assembly
      checkpoint at the onset of mitosis. Over expression of MPS1 correlated with a
      wide range of human tumors makes it an attractive target for finding an effective
      and specific inhibitor. In this work, we performed molecular dynamics simulations
      of protein MPS1 itself as well as protein bound systems with the inhibitor and
      natural substrate based on crystal structures. The reported orally bioavailable 1
      h-pyrrolo [3,2-c] pyridine inhibitors of MPS1 maintained stable binding in the
      catalytic site, while natural substrate ATP could not stay. Comparative study of
      stability and flexibility of three systems reveals position shifting of beta
      sheet region within the catalytic site, which indicates inhibition mechanism was
      through stabilizing the beta-sheet region. Binding free energies calculated with
      MM-GB/PBSA method shows different binding affinity for inhibitor and ATP.
      Finally, interactions between protein and inhibitor during molecular dynamic
      simulations were measured and counted. Residue Gly605 and Leu654 were suggested
      as important hot spots for stable binding of inhibitor by molecular dynamic
      simulation. Our results reveal an important position shifting within catalytic
      site for non-inhibited proteins. Together with hot spots found by molecular
      dynamic simulation, the results provide important information of inhibition
      mechanism and will be referenced for designing novel inhibitors.

PMID- 29380675
TI  - Multiscale simulation of the interaction of calreticulin-thrombospondin-1 complex
      with a model membrane microdomain.
AB  - Cell surface calreticulin (CRT) binding to thrombospondin-1 (TSP1), regulates
      cell adhesion, migration, anoikis resistance, and collagen production. Due to the
      essential role of membrane microdomains in CRT-mediated focal adhesion
      disassembly, we previously studied the effect of raft-like bilayers on TSP1-CRT
      interactions with all-atom molecular dynamics (AAMD) simulations. However, the
      simulated systems of protein on the surface of the bilayer(s) in the explicit
      solvent are too large for long timescale AAMD simulations due to computational
      expense. In this study, we adopted a multiscale modeling approach of combining
      AAMD, coarse-grained molecule dynamics (CGMD), and reversed AAMD (REV AAMD)
      simulations to investigate the interactions of single CRT or of the TSP1-CRT
      complex with a membrane microdomain at microsecond timescale. Results showed that
      CRT conformational stabilization by binding of TSP1 in AAMD simulation was
      undetectable in CGMD simulation, but it was recovered in REV AAMD simulation.
      Similarly, interactions of the CRT N-domain and TSP1 with the membrane
      microdomain were lost in CGMD simulations but they were re-gained in the REV AAMD
      simulations. There was the higher coordination of the CRT P-domain in the TSP1
      CRT complex with the lipid components of membrane microdomain compared to that of
      single CRT, which could directly affect the conformation of CRT and further
      mediate CRT recruitment of LDL receptor-related protein for signaling events.
      This study provides structural and molecular insights into TSP1-CRT interactions
      in a membrane microdomain environment and demonstrates the feasibility of using
      multiscale simulations to investigate the interactions between protein and
      membrane microdomains at a long timescale.

PMID- 29380677
TI  - Editor's Corner.

PMID- 29380676
TI  - The current role of glycopeptides in the treatment of methicillin-resistant
      Staphylococcus aureus (MRSA) infections in not neutropenic adults: the viewpoint
      of a group of Italian experts.
AB  - Staphylococcus aureus is still an important problem in clinical and therapeutic
      area, worldwide. In Italy, in recent years, methicillin resistance remained
      stable, yet considerably high, the percentage of strains of MRSA being around
      40%. It was deemed interesting and timely to carry out a consensus conference
      using the RAND/UCLA method to collect the opinion of a group of experts in
      infectious diseases on the role of glycopeptides in the management of MRSA
      infections within several clinical scenarios and namely in pneumonia, bacteremia
      and endocarditis, joint replacement infections, skin and soft tissue infections,
      diabetic foot, abdominal infections and central nervous system infections. The
      scenarios proposed by the Scientific Committee have been validated by a group of
      experts in infectious diseases and then voted in three meetings of infectious
      disease specialists. The results obtained on each individual condition were
      analyzed and therapeutic recommendations on each of these were released.

PMID- 29380678
TI  - Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the
      American Society of Clinical Oncology.
AB  - A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of
      publishing an annual report on the most transformative research occurring in
      cancer care. Thirteen reports later, the progress we have chronicled is
      remarkable, and this year is no different. The research featured in ASCO's
      Clinical Cancer Advances 2018 report underscores the impressive gains in our
      understanding of cancer and in our ability to tailor treatments to tumors'
      genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy,
      allows clinicians to genetically reprogram patients' own immune cells to find and
      attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell
      therapy-a type of adoptive cell immunotherapy-has led to remarkable results in
      young patients with acute lymphoblastic leukemia (ALL) and in adults with
      lymphoma and multiple myeloma. Researchers are also exploring this approach in
      other types of cancer. This advance would not be possible without robust federal
      investment in cancer research. The first clinical trial of CAR T-cell therapy in
      children with ALL was funded, in part, by grants from the National Cancer
      Institute (NCI), and researchers at the NCI Center for Cancer Research were the
      first to report on possible CAR T-cell therapy for multiple myeloma. These
      discoveries follow decades of prior research on immunology and cancer biology,
      much of which was supported by federal dollars. In fact, many advances that are
      highlighted in the 2018 Clinical Cancer Advances report were made possible thanks
      to our nation's support for biomedical research. Funding from the US National
      Institutes of Health and the NCI helps researchers pursue critical patient care
      questions and addresses vital, unmet needs that private industry has little
      incentive to take on. Federally supported cancer research generates the
      biomedical innovations that fuel the development and availability of new and
      improved treatments for patients. We need sustained federal research investment
      to accelerate the discovery of the next generation of cancer treatments. Another
      major trend in this year's report is progress in precision medicine approaches to
      treat cancer. Although precision medicine offers promise to people with cancer
      and their families, that promise is only as good as our ability to make these
      treatments available to all patients. My presidential theme, "Delivering
      Discoveries: Expanding the Reach of Precision Medicine," focuses on tackling this
      formidable challenge so that new targeted therapies are accessible to anyone who
      faces a cancer diagnosis. By improving access to high-quality care, harnessing
      big data on patient outcomes from across the globe, and pursuing innovative
      clinical trials, I am optimistic that we will speed the delivery of these most
      promising treatments to more patients. Sincerely, Bruce E. Johnson, FASCO ASCO
      President, 2017 to 2018.

PMID- 29380679
TI  - Effect of Motion Perception on Intertemporal Choice Is Associated With the
      Altered Time Perception.
AB  - Intertemporal choice refers to the choice between receiving a small immediate
      reward or a large delayed one. Previous studies have indicated that time
      perception plays a critical role in the intertemporal choice, and it could be
      affected by the features of the target stimulus in the time reproduction task,
      such as speed of movement and state of motion. However, there is no evidence
      about whether backward or forward motion perception could alter the intertemporal
      choice. Thus, in our current study, 29 participants were asked to perform two
      tasks in a random order. One was the intertemporal choice task after viewing
      videos containing moving elements with forward/backward directions as well as
      stationary ones, and another was the time perception task. We found that the
      discounting rate in intertemporal choice was significantly larger in backward
      motion condition than in both forward motion and stationary conditions,
      indicating that backward motion perception made participants more myopic
      (specifically, more likely to choose the smaller immediate reward instead of the
      large delayed one) during their decision-makings. Meanwhile, participants
      overestimated the temporal duration in a time perception task in backward motion
      condition compared to the other two conditions. Furthermore, the Pearson's
      correlation analysis showed that the changes of the intertemporal choice induced
      by backward motion perception could be associated with the altered time
      perception. As far as we know, we provide the first evidence on influence of
      motion perception on the intertemporal choice as well as its possible cognitive
      correlates, which extend previous studies on cognitive basis of the intertemporal
      choices.

PMID- 29380680
TI  - Power Moderates the Effects of Social Dominance Orientation on Punishment: An
      Experimental Analysis.
AB  - In this study, it was hypothesized that experimentally manipulated levels of
      power would moderate the association of dispositional social dominance
      orientation (SDO) with preferences for harsh punishment. In particular, we
      expected to detect a stronger effect for dispositional SDO in the low-power
      condition, relying on the notion that low power enhances sensitivity to threats
      to the status quo, and that high SDO individuals are particularly motivated to
      enforce hierarchy-enhancing measures as punishment. SDO scores were measured two
      months prior to the experiment, and then immediately after the experimental
      session. As expected, preexperimental SDO interacted with the power manipulation.
      We found stronger preexperimental SDO effects on punishment among low-power
      participants. We also anticipated and found that individuals high in SDO
      increased further their postexperimental SDO scores if assigned to a high-power
      condition. The discussion focuses on the importance of SDO effects among low
      status groups and on how situational roles shape dispositional self-descriptions.

PMID- 29380681
TI  - Multidimensionality of the Langner Symptom Survey and Replication of a Cutoff
      Score in Emerging Adults.
AB  - This study investigated the dimensionality of the Langner Symptom Survey and
      replicated a recent finding regarding a clinically validated cutoff score in
      emerging adults. Nine hundred thirteen (631 females and 282 males) students at a
      private university in the Midwestern United States participated online as part of
      a larger study and completed the Langner Symptom Survey and a demographic
      questionnaire. Results from exploratory principal components and confirmatory
      factor analyses provided support for both a six- and three-factor model of the
      Langner Symptom Survey, with the three-factor model offering marginally better
      confirmatory fit indices and greater parsimony of interpretation. A cutoff score
      of 5 denoting clinically significant psychological distress and need for
      treatment was supported through analysis of receiver-operating characteristic,
      sensitivity, specificity, and total classification accuracy based on
      psychological service utilization, and this result successfully replicated a
      recently published finding. The Langner Symptom Survey may function as a
      multidimensional measure of psychological distress and need for treatment in
      emerging adults that may need a lexical update.

PMID- 29380682
TI  - The effect of chronic conditions and multi-morbidity on self-assessed health in
      Russia.
AB  - AIMS: Chronic disorders, such as cardiovascular disease, cancer, respiratory
      diseases and diabetes, are the leading cause of mortality globally, representing
      68% of all recorded deaths. The incidence of chronic disease and multiple chronic
      disease is rising across the world, but relatively little is known about the
      impact of multi-morbidities on the life experiences of those individuals who
      encounter them. In this paper, we examine and quantify the relationship between
      chronic illness, multi-morbidity and the individual self-assessed health of the
      Russian population using individual-level Russian data and a novel quantitative
      technique. METHODS: We apply a partial proportional odds framework to a rich data
      set incorporating demographic, socio-economic and health indicators in Russia.
      RESULTS: We find that individuals with chronic conditions report significantly
      lower levels of health than those without chronic conditions, but that the
      strength of the effect is much more pronounced for males than for females (e.g.
      neurological disease: odds ratio [OR]=4.81 for men; OR=1.86 for women)). As the
      number of co-morbidities increases, there is a dramatic decrease in the
      likelihood of reporting good health for both males and females, but for males
      there is a greater increase in the likelihood of reporting bad health (OR=49.31
      for males with >=5 diseases; OR=28.05 for females). CONCLUSIONS: More than 40% of
      Russians currently live with multi-morbidity, and this group is at the highest
      risk of reporting poor self-rated health. This research adds to the body of
      evidence demonstrating the challenges facing health-care systems as new patterns
      of disease take hold in contemporary society.

PMID- 29380683
TI  - Resting-state fMR evidence of network reorganization induced by navigated
      transcranial magnetic repetitive stimulation in phantom limb pain.
AB  - Objectives Repetitive transcranial magnetic stimulation (rTMS) is a promising
      tool for treatment of chronic pain. We describe the use of navigated rTMS to
      treat a patient affected by phantom limb pain (PLP) and to modulate brain
      functional connectivity. We reviewed the literature on the use of rTMS as a tool
      for relieving central pain by promoting brain plasticity. Methods A 69-year-old
      patient came to our observation blaming severe pain (Visual Analog scale, VAS,
      score 9) to a phantom right lower limb. We mapped left primary motor area (PMA)
      by navigated TMS and assessed connectivity with resting-state functional MR
      (rsfMR). The patient underwent 30-days navigated rTMS treatment. We applied low
      frequency stimulation (1 Hz) over the primary somatosensory area (PSA) and high
      frequency stimulation (10 Hz) over PMA and dorsolateral prefrontal cortex (DLPFC)
      of the left hemisphere. Results This strategy allowed a pain relief with a
      reduction of 5 points of the VAS score after 1 month. Post-treatment rsfMR showed
      increased connectivity, mainly in the sensory-motor network and the unaffected
      hemisphere (P < 0.05). Discussion This report represents a proof-of-concept that
      navigated rTMS can be effectively used to stimulate selected brain areas in PLP
      patients in order to promote brain connectivity, and that rsfMR is a useful tool
      able to analyze functional results. In the literature, we found data supporting
      the assumption that, in patients affected by PLP, a reduced connectivity in
      interhemispherical and sensory-motor network plays a role in generating pain and
      that rTMS has the potential to restore impaired connectivity.

PMID- 29380684
TI  - Relative orientation of collagen molecules within a fibril: a homology model for
      homo sapiens type I collagen.
AB  - Type I collagen is an essential extracellular protein that plays an important
      structural role in tissues that require high tensile strength. However, owing to
      the molecule's size, to date no experimental structural data are available for
      the Homo sapiens species. Therefore, there is a real need to develop a reliable
      homology model and a method to study the packing of the collagen molecules within
      the fibril. Through the use of the homology model and implementation of a novel
      simulation technique, we have ascertained the orientations of the collagen
      molecules within a fibril, which is currently below the resolution limit of
      experimental techniques. The longitudinal orientation of collagen molecules
      within a fibril has a significant effect on the mechanical and biological
      properties of the fibril, owing to the different amino acid side chains available
      at the interface between the molecules.

PMID- 29380685
TI  - The (Non)Impact of the 2015 Paris Terrorist Attacks on Political Attitudes.
AB  - Previous research has consistently found widespread attitudinal impacts of
      terrorist attacks. Using data from the European Social Survey, which was
      conducting interviews in 11 countries when the Charlie Hebdo attacks happened in
      January 2015, I compare respondents from before and after the shootings to test
      whether the event shifted public opinion on several topics. There is no evidence
      of average impacts across a range of issues, from xenophobia to ideological self
      placement and immigration policy preferences. Data collected when the Paris
      November 2015 shootings happened also present no evidence of public opinion
      change on immigration and refugee policy matters in France, but there appears to
      be an effect in other countries-which varies according to contextual
      vulnerability. Results suggest that views on immigration and immigrants have, to
      a certain extent, stabilized in Europe and are less susceptible to shifts from
      dramatic events.

PMID- 29380687
TI  - Disclosure of sexual orientation by gay, bisexual and other men who have sex with
      men to healthcare.

PMID- 29380686
TI  - Behavioral Adjustment Moderates the Link Between Neuroticism and Biological
      Health Risk: A U.S.-Japan Comparison Study.
AB  - Neuroticism, a broad personality trait linked to negative emotions, is
      consistently linked to ill health when self-report is used to assess health.
      However, when health risk is assessed with biomarkers, the evidence is
      inconsistent. Here, we tested the hypothesis that the association between
      neuroticism and biological health risk is moderated by behavioral adjustment, a
      propensity to flexibly adjust behaviors to environmental contingencies. Using a
      U.S.-Japan cross-cultural survey, we found that neuroticism was linked to lower
      biological health risk for those who are high, but not low, in behavioral
      adjustment. Importantly, Japanese were higher in behavioral adjustment than
      European Americans, and as predicted by this cultural difference, neuroticism was
      linked to lower biological health risk for Japanese but not for European
      Americans. Finally, consistent with prior evidence, neuroticism was associated
      with worse self-reported health regardless of behavioral adjustment or culture.
      Discussion focused on the significance of identifying sociocultural correlates of
      biological health.

PMID- 29380689
TI  - Chemometric Analysis for the Classification of some Groups of Drugs with
      Divergent Pharmacological Activity on the Basis of some Chromatographic and
      Molecular Modeling Parameters.
AB  - AIM AND OBJECTIVE: In this study, chemometric methods as correlation analysis,
      cluster analysis (CA), principal component analysis (PCA), and factor analysis
      (FA) have been used to reduce the number of chromatographic parameters
      (logk/logkw) and various (e.g., 0D, 1D, 2D, 3D) structural descriptors for three
      different groups of drugs, such as 12 analgesic drugs, 11 cardiovascular drugs
      and 36 "other" compounds and especially to choose the most important data of
      them. MATERIAL AND METHODS: All chemometric analyses have been carried out,
      graphically presented and also discussed for each group of drugs. At first,
      compounds' structural and chromatographic parameters were correlated. The best
      results of correlation analysis were as follows: correlation coefficients like R
      = 0.93, R = 0.88, R = 0.91 for cardiac medications, analgesic drugs, and 36
      "other" compounds, respectively. Next, part of molecular and HPLC experimental
      data from each group of drugs were submitted to FA/PCA and CA techniques.
      RESULTS: Almost all results obtained by FA or PCA, and total data variance, from
      all analyzed parameters (experimental and calculated) were explained by first
      two/three factors: 84.28%, 76.38 %, 69.71% for cardiovascular drugs, for
      analgesic drugs and for 36 "other" compounds, respectively. Compounds clustering
      by CA method had similar characteristic as those obtained by FA/PCA. In our
      paper, statistical classification of mentioned drugs performed has been widely
      characterized and discussed in case of their molecular structure and
      pharmacological activity. CONCLUSION: Proposed QSAR strategy of reduced number of
      parameters could be useful starting point for further statistical analysis as
      well as support for designing new drugs and predicting their possible activity.

PMID- 29380690
TI  - Protein Sequence Comparison and DNA-binding Protein Identification with
      Generalized PseAAC and Graphical Representation.
AB  - AIM AND OBJECTIVE: The rapid increase in the amount of protein sequence data
      available leads to an urgent need for novel computational algorithms to analyze
      and compare these sequences. This study is undertaken to develop an efficient
      computational approach for timely encoding protein sequences and extracting the
      hidden information. METHODS: Based on two physicochemical properties of amino
      acids, a protein primary sequence was converted into a three-letter sequence, and
      then a graph without loops and multiple edges and its geometric line adjacency
      matrix were obtained. A generalized PseAAC (pseudo amino acid composition) model
      was thus constructed to characterize a protein sequence numerically. RESULTS: By
      using the proposed mathematical descriptor of a protein sequence, similarity
      comparisons among beta-globin proteins of 17 species and 72 spike proteins of
      coronaviruses were made, respectively. The resulting clusters agreed well with
      the established taxonomic groups. In addition, a generalized PseAAC based SVM
      (support vector machine) model was developed to identify DNA-binding proteins.
      Experiment results showed that our method performed better than DNAbinder, DNA
      Prot, iDNA-Prot and enDNA-Prot by 3.29-10.44% in terms of ACC, 0.056-0.206 in
      terms of MCC, and 1.45-15.76% in terms of F1M. When the benchmark dataset was
      expanded with negative samples, the presented approach outperformed the four
      previous methods with improvement in the range of 2.49-19.12% in terms of ACC,
      0.05-0.32 in terms of MCC, and 3.82- 33.85% in terms of F1M. CONCLUSION: These
      results suggested that the generalized PseAAC model was very efficient for
      comparison and analysis of protein sequences, and very competitive in identifying
      DNA-binding proteins.

PMID- 29380691
TI  - Advances in Nanostructure-mediated Hyperthermia in Tumor Therapies.
AB  - BACKGROUND: Hyperthermia has been proposed as a promising treatment modality for
      its advantageous profiles such as mini/non-invasiveness, good tolerability and
      cost-effectiveness. Quick development of nanotechnology in recent years has
      greatly broadened the application area of hyperthermia and endowed it with
      attractive new functions. This review aims to present an overview of different
      nanostructures mediated hyperthermia in terms of external stimuli source.
      METHODS: We performed to review for the development and current status of
      nanostructure-mediated hyperthermia, by searching MEDLINE, EMBASE, and Cochrane
      Library database for identification of relevant articles. RESULTS: In the present
      study, the systemic results of hyperthermia mediated by nanostructures were
      researched, and five different kinds of external sources were found and listed in
      this review. The brief mechanism and commonly explored nanostructures were
      introduced and then combined therapies of nanostructure-mediated hyperthermia
      stimulated by different external sources were investigated. Finally, challenges
      with current nanostructures mediated hyperthermia were discussed in order to give
      advice to the future development of nanostructure-mediated hyperthermia.
      CONCLUSIONS: Despite all the achievements the new technology of nanostructure
      mediated hyperthermia have made in pre-clinical animal experiments, there are
      still much to be pursued in the further development to be biocompatible,
      effective and precise.

PMID- 29380692
TI  - Cross-regulatory circuit between AHR and microbiota.
AB  - The gut microbes have a close symbiotic relationship with their host.
      Interactions between host and the microbiota affect the nutritional,
      immunological, and physiological status of the host. The aryl hydrocarbon
      receptor (AHR) is a ligand activated transcription factor that mediates the
      toxicity of xenobiotics. Recently, the relationship between the gut microbiota
      and AHR has attracted the attention of many researchers. The AHR influences the
      intestinal microbiota population and mediates host-microbe homeostasis.
      Interestingly, the gut microbiota also produces ligands of AHR from bacterial
      metabolism and thereby activates the AHR signaling pathway. This review presents
      current knowledge of the cross-regulatory circuit between the AHR and intestinal
      microbiota.

PMID- 29380693
TI  - Hepatitis C Virus Mediated Metastasis in Hepatocellular Carcinoma as a
      Therapeutic Target for Cancer Management.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common causes of
      cancer associated deaths. Prognosis is relatively poor in cases where Hepatitis C
      Virus (HCV) is associated as causative agent, mainly due to increased risk of
      metastasis. Metastasis is the major cause of all cancer related deaths. METHODS:
      We reviewed reports linking expression of HCV encoded proteins with changes in
      cellular functions. We also compared reports on HCV-induced HCC with those on non
      viral and Hepatitis B Virus (HBV) induced HCC. Novel therapeutic approaches for
      handling metastatic HCC were also reviewed. RESULTS: HCV infection is associated
      with expression of multiple pro-metastatic factors in HCC patients. HCV encoded
      proteins can directly induce pro-metastasis cellular functions. HCV-induced HCC
      has a greater chance of recurrence than any non-viral and Hepatitis B Virus (HBV)
      induced HCC. Recent advances in understanding of evolutionary dynamics of tumor
      argue that trying to prevent spreading of cancer may ultimately prove to be a
      better approach than striving to cure it. Inhibiting the metastasis can thereby
      substantially increase the survival period in patients. Host cell protein Nm23-H1
      is a known suppressor of tumor metastasis and has been shown to be modulated by
      proteins encoded by different viruses associated with cancers. CONCLUSION: Nm23
      H1 is an important therapeutic target for virus mediated malignancies. This
      review is an attempt to summarize the current state of understanding of cancer
      cell metastasis in HCV induced tumors, and argues for approaches based on
      targeting host and viral factors critical for cancer metastasis as therapeutic
      targets.

PMID- 29380694
TI  - Herbal Immunomodulators - A Remedial Panacea for Designing and Developing
      Effective Drugs and Medicines: Current Scenario and Future Prospects.
AB  - BACKGROUND: Constant exposure to various stressors, such as immune pressure,
      rapidly increasing population, deleterious changes in the ecosystem, climate
      change, infection with emerging and re-emerging pathogens, and fast-paced
      lifestyle, is a critical factor in the globally increasing incidences of
      immunocompromising health conditions, as well as stress. Synthetic
      chemotherapeutic agents, which are widely available in the commercial market, may
      be highly efficacious, but most are immunosuppressive and exert many side
      effects. METHODS: Herein, we comprehensively reviewed current literature from
      various scientific databases such as Bentham Science, PubMed, Scopus, Elsevier,
      Springer, etc. The inclusion/exclusion criteria based on literature with high
      importance was adopted to analyze and compile salient information from the
      authentic bibliographic sources. RESULTS: Undoubtedly, the pivotal
      characteristics of immunostimulants and immunomodulators in the maintenance of
      the health and productivity of humans, as well as animals, cannot be overlooked.
      Numerous herbs used in ethnoveterinary medicine can be successfully employed as
      adjuvant rehabilitators to negate the deleterious effects of chemotherapeutics.
      The sources of these medicinal remedies are part of long traditions in different
      regions of the world, such as Indian Ayurveda and Traditional Chinese Medicine,
      which have been developed through empirical experience. Traditional medicine
      employs a holistic approach to the prevention of disease, and traditional herbal
      medicines are a source of many components with a high therapeutic value that are
      used in modern allopathic medicine. Globally, many studies have been conducted on
      these herbs and have revealed unique active constituents that activate the innate
      immune system through the stimulation of macrophages and lymphocytes, and
      modulation of the cytokine profile, which leads to a state of alertness with a
      subsequent reduction in the incidence of infection. Immunomodulatory constituents
      with herbal origins are termed as phytochemicals, including flavonoids,
      glycosides, polysaccharides, terpenoids, essential oils, various bitters, and
      alkaloids; all these compounds exert vital, multidimensional effects. Efforts
      have focused on screening plant preparations to identify adjuvant immune
      properties; furthermore, several potent phytol adjuvants have been experimentally
      proven to downregulate inflammatory reactions in addition to enhance specific
      adaptive responses to vaccines. CONCLUSIONS: In summary, this review summarizes
      the current status and future prospects regarding the immunomodulatory potential
      of various herbs and plants and their promising utility for designing and
      developing effective drugs and medicines in safeguarding the health of humans,
      animals, and poultry.

PMID- 29380695
TI  - How to Control Asthma with Personalized Management: Where Do We Stand Now?
AB  - Asthma is one of the most significant diseases worldwide and causes overwhelming
      costs physically and economically. The heterogeneity of asthma has been a hot
      topic, and an increasing amount of research has been conducted on this issue. The
      study of asthma has revealed various groups of asthma patients who share
      phenotypic characteristics that naturally elicit the need for personalized asthma
      therapy. Clinical evidence has shown that a 'one size fits all' approach does not
      apply to all asthma patients because of the large variability in treatment
      responses to asthma medication. Attention should be given to patients who do not
      respond to normal treatment to avoid increasing the risk of exacerbation and
      meaningless costs. An increasing amount of pharmacogenetics research, genotype
      based trials and precision medicine trials have been conducted to investigate
      this problem. Our review will focus on the three most widely used treatments for
      asthma management, which are b-adrenergic receptor agonists, inhaled
      corticosteroids (ICS) and anti-leukotriene modifiers. We summarize the existing
      loci reported in the literature that are potentially associated with drug
      responses to typically used medications, suggesting that a genetic test with high
      predictive accuracy could predict therapeutic responses, and proper management
      can be achieved in asthma patients. This personalized approach to curative
      medicine should make way for the realization of personalized preventive and
      predictive medicine in the coming years.

PMID- 29380696
TI  - Kisspeptin and its effect on mammalian spermatogensis.
AB  - Kisspeptin and its receptor, GPR54, are regarded as key regulators of and
      catalysts for male puberty onset, and also fundamental gatekeepers of
      spermatogenesis in mammals. Consequently, the loss function of kisspeptin or
      GPR54 leads to a symptom of hypogonadotropic hypogonadism (HH) in human and HH
      accompanied by lower gonadotrophic hormone levels, smaller testes, impaired
      spermatogenesis and abnormal sexual maturation in mice. Besides its well-
      recognized functions in hypothalamus before and during puberty, accumulating data
      strongly support kisspeptin production in tests, and participation in somatic and
      germ cell development and sperm functions as well. This review summarizes the
      published data from animal models and humans in in vivo and in vitro studies
      regarding the testicular activity of kisspeptins to conserve male fertility.
      Kisspeptin might be a new potential therapeutic target for the treatment of male
      fertility defects and disorders.

PMID- 29380697
TI  - Medicinal and Therapeutic Potential of Herbs and Plant Metabolites / Extracts
      Countering Viral Pathogens - Current Knowledge and Future Prospects.
AB  - BACKGROUND: Recently, there has been a remarkable progress in the field of
      antiviral herbal therapy owing to increasing concerns about the development of
      drug resistance and limited advances in the field of antiviral drug discovery. In
      almost all countries, medicinal plants have been used widely throughout history
      for the treatment of diseases and infections as traditional healing remedies due
      to their broad therapeutic spectrum and minimal or no side effects. As synthetic
      antiviral drugs are not available against most of the viral agents, hence all
      possible efforts have been focused on the search for new drugs and
      complementary/alternative medicines from different herbal formulations. METHODS:
      We have retrieved the related information from the online published resources
      (Medline, PubMed, Pub- Med Central, Science Direct and other scientific
      databases); which were further analyzed and compiled. RESULTS: Medicinal plants
      contain extractable biochemical and bioactive compounds, which can target certain
      viruses or can cure or prevent several viral diseases and infections. Despite
      their long history of use, the research and scientific evidences regarding the
      use of medicinal plants and natural products as prophylactics, therapeutics, and
      their health multiple beneficial applications have only gained momentum in past
      few decades. Many scientific studies have been undertaken, which range from the
      separation of active substances to the comprehension of the therapeutic
      mechanisms of antiviral herbs, their potent applications in the neutralization of
      viral pathogens and clinical trials. Consequently, hundreds of herbs and plant
      metabolites have been screened, identified, and tested for their antiviral
      activities; fortunately, some have shown significant medicinal activity in the
      amelioration or prevention of various viral diseases in both preclinical and
      clinical studies. CONCLUSION: This review addresses the scientific significance
      of various herbal formulations of different medicinal plants and their extracts,
      which have shown promise or been proven effective for the treatment of diseases
      caused by various viral pathogens, including emerging and re-emerging viruses
      that infect humans, animals, poultry and fish.

PMID- 29380699
TI  - Relationship between CNS and Immunology: Correlation with Psychology.
AB  - BACKGROUND: Higher animals, especially the human beings have the privilege of
      employing advanced central nervous system (CNS) as well as the evolved immune
      system to ward off various onslaughts throughout their life. Alterations in
      inflammatory and neural regulatory pathways lead to several disorders that are
      now becoming the cause of concern across the world. Deregulation in bidirectional
      network, particularly in aging population, leads to several neurodegenerative
      diseases such as dementia as a one of the major characteristics. OBJECTIVE:
      Interestingly, research updates have signified the role of abrupt immune
      regulation in several brain diseases, establishing a link between altered immune
      system and CNS related diseases. In the later period of life, the altered immune
      response in the pathogenesis of major psychiatric disorders, has become more
      visible. In the present manuscript, we present a synopsis on the linkage of CNS
      and immune system with respect to psychology, with the aim to further understand
      the biological machinery of psychoneuroimmunological disorders. The immune system
      of human being plays an important role in keeping pathogen onslaughts on bay.
      CONCLUSION: Our manuscript concludes a close relationship between emotion and
      psychology to diseases and immunology, proclaiming the need of providing enhanced
      attention on mechanistic aspect of psychoneuroimmunological disorders.

PMID- 29380700
TI  - Role of Interleukin 28B Polymorphisms in Response to Interferon Based Therapy for
      Hepatitis C Virus Clearance.
AB  - BACKGROUND: Interleukin-28B (IL28B) locus on a human chromosomal region mapped to
      19q13 execute immune defense against viruses. During Hepatitis C Virus (HCV)
      infection the IL28B has a promising role in deciding the consequence of infection
      for spontaneous clearance of viruses or causing chronic liver infection.
      Treatment of chronic hepatitis C includes use of direct acting antivirals,
      Pegylated-Interferon (PEG-IFN) and Ribavirin (RBV) therapy. Also, interferon free
      regimens are suggested to be useful in resistant patients. Numerous reports
      including Genome-Wide Association Studies (GWAS), comprehensive meta-analysis and
      independent case-control studies in different population have revealed the
      association between certain Il-28B polymorphisms and response to the PEGIFN- RBV
      therapy in patients infected with HCV. METHOD: We searched all peer-reviewed
      relevant and recent literature manually for the present review. CONCLUSION: The
      GWAS studies have revealed an important role of IL28B in HCV infection, which was
      supported by many independent studies and meta-analysis by different groups in
      different ethnicities. IL28B genotyping may be use as predictors of response for
      IFN-based therapy and personalized treatment of hepatitis C patient.

PMID- 29380701
TI  - The expression of dopamine receptors gene and their potential role in targeting
      breast cancer cells with selective agonist and antagonist drugs. Could it be the
      novel insight to therapy?
AB  - BACKGROUND: Breast cancer is one of the common causes of mortality for women in
      Iran and other parts of the world. The substantial increasing rate of breast
      cancer in both developed and developing countries warns the scientists to provide
      more preventive steps and therapeutic measures. This study is conducted to
      investigate the impact of neurotransmitters (e.g., Dopamine) through their
      receptors and the importance of cancers via damaging immune system. It also
      evaluates dopamine receptors gene expression in the women with breast cancer at
      stages II or III and dopamine receptor D2 (DRD2) related agonist and antagonist
      drug effects on human breast cancer cells, including MCF-7 and SKBR-3. METHODS:
      The patients were categorized into two groups: 30 native patients who were
      diagnosed with breast cancer at stages II and III, with the mean age of 44.6
      years and they were reported to have the experience of a chronic stress or
      unpleasant life event. The second group included 30 individuals with the mean age
      of 39 years as the control group. In order to determine the RNA concentration in
      all samples, the RNA samples were extracted and cDNA was synthesized. The MCF-7
      cells and SKBR-3 cells were treated with dopamine receptors agonists and
      antagonists. The MTT test was conducted to identify oxidative and reductive
      enzymes and to specify appropriate dosage at four concentrations of dopamine and
      Cabergoline on MCF-7 and SKBR-3 cells. Immunofluorescence staining was done by
      the use of a mixed dye containing acridine orange and ethidiume bromide on
      account of differentiating between apoptotic and necrotic cells. Flow cytometry
      assay was an applied method to differentiate necrotic from apoptotic cells.
      RESULTS: Sixty seven and thirty three percent of the patients were related to
      stages II and III, respectively. About sixty three percent of the patients
      expressed ER, while fifty seven percent expressed PR. Thirty seven percent of the
      patients were identified as HER-2 positive. All types of D2-receptors were
      expressed in PBMC of patients with breast cancer and healthy individuals. The
      expression of the whole dopamine receptor subtypes (DRD2-DRD4) was carried out on
      MCF-7 cell line. The results of RT-PCR confirmed the expression of DRD2 on SKBR-3
      cells, whereas the other types of D2- receptors did not have an expression The
      remarkable differences in gene expression rates between patients and healthy
      individuals were revealed in the result of the Real-time PCR analysis. The over
      expression in DRD2 and DRD4 genes of PBMCs was observed in the patients with
      breast cancer at stages II and III. The great amount of apoptosis and necrosis
      occurred after the treatment of MCF-7 cells by Cabergoline from 25 to 100 umolL-1
      concentrations. CONCLUSION: This study revealed the features of dopamine
      receptors associated with apoptosis induction in breast cancer cells. Moreover,
      the use of D2-agonist based on dopamine receptors expression in various breast
      tumoral cells could be promising as a new insight of complementary therapy in
      breast cancer.

PMID- 29380698
TI  - Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney
      Transplantation.
AB  - BACKGROUND: Tacrolimus (Tac, or FK506), a calcineurin inhibitor (CNI), is the
      first-line immunosuppressant which consists of the footstone as immunosuppressive
      regimens in kidney transplantation. However, the drug toxicity and the
      significant differences of pharmacokinetics (PK) and pharmacodynamics (PD) among
      individuals are hidden troubles for clinical application. Recently, emerging
      evidences of Tac pharmacogenetics (PG) regarding drug absorption, metabolism,
      disposition, excretion and response are discovered for better understanding of
      this drug. METHOD: We reviewed the published articles regarding the Tac PG and
      its effects on PK and PD in kidney transplantation. In addition, we summarized
      information on polygenic algorithms. RESULTS: The polymorphism of genes encoding
      metabolic enzymes and transporters related to Tac were largely investigated, but
      the results were inconsistent. In addition to CYP3A4, CYP3A5 and P-gp (also known
      as ABCB1), single nucleotide polymorphisms (SNPs) might also affect the PK and PD
      parameters of Tac. CONCLUSION: The correlation between Tac PK, PD and PG is very
      complex. Although many factors need to be verified, it is envisaged that thorough
      understanding of PG may assist clinicians to predict the optimal starting dosage,
      help adjust the maintenance regimen, as well as identify high risk patients for
      adverse effects or drug inefficacy.

PMID- 29380702
TI  - Biological and Genetic Features of Neuroblastoma and Their Clinical Importance.
AB  - Neuroblastoma derived from primitive cells of the sympathetic nervous system
      typically develops in the adrenal medulla or paraspinal ganglia. Neuroblastoma
      usually occurs sporadically, but familial cases are also observed. ALK and PHOX2B
      germline mutations can cause hereditary neuroblastoma, while a common genetic
      variation in chromosome 6p22 is associated to sporadic neuroblastoma. However,
      the aetiology of sporadic neuroblastoma is not exactly known. This embryonic
      malignancy generally represents the second most common solid tumour after central
      nervous system tumours throughout the world in childhood. Neuroblastoma is a
      complex disease that has different clinical courses, from metastatic spread to
      spontaneous regression. Spontaneous regression can occur without therapy in
      primary or metastatic site. Potential regression mechanisms primarily involve
      apoptosis, hypermethylation of subtelomeric DNA, immune response and Nerve Growth
      Factor (NGF) deprivation. Neuroblastoma is a heterogeneous tumour that can show
      many different chromosomal abnormalities; e.g. MYCN amplification, 1p deletion,
      unbalanced translocations involving chromosome 17, aneuploidies and Loss of
      Heterozygosity (LOH) events. Tyrosine kinase receptors TrkA, TrkB and TrkC, their
      ligands NGF, Brain-derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3),
      and Aurora Kinase A (AURKA) play a regulatory role in differentiation, apoptosis,
      cell proliferation, tumourigenesis, angiogenesis or metastasis of neuroblastoma.
      TrkA expression is associated with differentiation or regression, depending on
      presence or absence of NGF, whereas TrkB and BDNF are mostly expressed in
      aggressive neuroblastomas with MYCN amplification. MYCN is amplified in 18-38% of
      neuroblastoma cases. MYCN amplification mechanism remains to be completely
      clarified. This paper reviews the biological/genetic features and their clinical
      importance in neuroblastoma.

PMID- 29380703
TI  - Structural Basis of Antisickling Effects of Selected FDA Approved Drugs: A Drug
      Repurposing Study.
AB  - INTRODUCTION: Sickle cell disease is characterized by a point mutation involving
      substitution of glutamic acid at position 6 to valine. Encoded in this
      hydrophobic mutation is both an intrinsic capacity for the beta globin molecules
      to assemble into thermodynamically favoured polymeric states as well as a
      rational way of interrupting the aggregation. METHODS: In this work, starting
      with a theoretical model that employs occlusive binding onto the beta globin
      aggregation surface and using a range of computational methods and an effective
      energy for screening, a number of FDA approved drugs with computed aggregation
      inhibitory activities were identified. RESULTS AND CONCLUSION: The validity of
      the model was confirmed using sickling tests, after which pharmacophore models as
      well the structural basis for the observed antisickling effects were identified.

PMID- 29380704
TI  - The Influence of Ageing and Gender in Musculoskeletal Stem Cell.
AB  - BACKGROUND: Multipotent Mesenchymal Stromal Cells (MSCs) are the most common type
      of stem cell used in the regeneration of skeletal tissue. These cells have
      multipotent, angiogenic, paracrine, anti-fibrotic and immunological properties.
      They are readily available, easily isolated and have many therapeutic
      applications. The ageing population is on the increase and with this comes an
      upsurge in medical conditions that may benefit from novel stem cell-based
      therapies to treat ageingassociated diseases. Given that autologous implantations
      have shown to be beneficial in these targeted therapies, questions are raised
      regarding the effect of ageing and gender on the efficacy of stem cells.
      OBJECTIVE: In this review, we look at the ageing process and look at the effects
      of ageing and gender on the characterization, proliferation and differentiation
      of mesenchymal stem cells. We also discuss future therapeutic strategies that may
      be used to overcome these effects and cell senescence. CONCLUSION: Advancements
      in modern technology and experimental techniques have provided an insight into
      how ageing affects properties of MSCs. However, it is evident that further work
      needs to be conducted due to many mixed reviews and conflicting data. Given that
      the human life expectancy is expected to increase the topic of cell ageing and
      therapeutic applications will remain a hot topic in years to come.

PMID- 29380705
TI  - The Use of Electrospun Scaffolds in Musculoskeletal Tissue Engineering: A Focus
      on Tendon and the Rotator Cuff.
AB  - INTRODUCTION: Rotator Cuff tears affect 15% of 60 year olds and carry a
      significant social and financial burden. Current operative techniques and repair
      adjuncts are associated with unacceptably high failure rates, stimulating
      investigation into novel tissue engineering and regenerative medicine (TERM)
      approaches in the field of rotator cuff surgery. In this review we explore the
      most recent advances in the field of electrospinning, focussing on proposed
      tissue-engineered solutions in tendon, specifically the rotator cuff. METHODS:
      The MEDLINE/PubMed database was reviewed for English language papers and
      publication date within the last 5 years, using the search string
      "electrospinning AND tendon". RESULTS: Of 38 results, eighteen studies were
      included in the final analysis. Common themes identified included (1)
      drug/biological molecule delivery (2) using novel and biological materials in
      manufacture (3) increased mechanical strengths of materials, and, (4) techniques
      to improve the nanotopographical properties - of electrospun scaffolds. Human
      tissue was used in less than 15% of studies to determine cytocompatibility.
      Varying study designs were observed often employing differing outcome measures
      making direct comparisons and conclusions challenging. CONCLUSION: This review
      summarises the most current scientific knowledge in the study of TERM in tendon
      and the rotator cuff field and electrospinning techniques. We found that as
      knowledge of the pathology behind rotator cuff tears is furthered, specific
      molecules, mechanical properties and nanotopographical features are being
      incorporated into electrospun scaffolds.

PMID- 29380706
TI  - Anticancer Activity Study of Chromone and Coumarin Hybrids using Electrical
      Impedance Spectroscopy.
AB  - AIMS: Oncology treatments aim at selective toxicity for tumor (compared to
      normal) cells, and chromone- coumarin hybrids have shown such activity. METHODS:
      In this study, we test a novel series of synthetic chromone and coumarin
      derivatives (1-9) for cytotoxic activity against a panel of tumor cell lines (MCF
      7, A549, HepG2, HTC-116, B16 and Caco-2) opposed to non-tumor cells (HEK-293t).
      Electrical impedance spectroscopy was used to monitor cell viability in real
      time. RESULTS: Compound 8 showed the most potent activity, and it significantly
      diminished cancer cell proliferation and viability in different cell lines. It
      induced apoptosis in a dose-dependent manner, as shown by Western blot and flow
      cytometry. CONCLUSION: Electrical impedance spectroscopy appears to be a
      convenient tool for in vitro cytotoxicity analysis, which could be useful for
      identifying drug effects and side effects during early phases of drug discovery
      and development.

PMID- 29380707
TI  - Bacterial Conjunctivitis in Childhood: Etiology, Clinical Manifestations,
      Diagnosis, and Management.
AB  - BACKGROUND: Bacterial conjunctivitis is a common reason for children to be seen
      in pediatric practices. A correct diagnosis is important so that appropriate
      treatment can be instituted. OBJECTIVE: To provide an update on the evaluation,
      diagnosis, and treatment of bacterial conjunctivitis in children. METHODS: A
      PubMed search was completed in Clinical Queries using the key term "bacterial
      conjunctivitis". Patents were searched using the key term "bacterial
      conjunctivitis" from www.freepatentsonline.com and www.google.com/patents.
      RESULTS: In the neonatal period, bacterial conjunctivitis is rare and the most
      common cause of organism is Staphylococcus aureus, followed by Chlamydia
      trachomatis. In infants and older children, bacterial conjunctivitis is most
      often caused by Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella
      catarrhalis. Clinically, bacterial conjunctivitis is characterized by a purulent
      eye discharge, or sticky eyes on awakening, a foreign body sensation and
      conjunctival injection (pink eye). The diagnosis is made clinically. Cultures are
      unnecessary. Some authors suggest a watchful observation approach as most cases
      of bacterial conjunctivitis are self-limited. A Cochrane review suggests the use
      of antibiotic eye drops is associated with modestly improved rates of clinical
      and microbiological remission as compared to the use of placebo. Various
      investigators have also disclosed patents for the treatment of conjunctivitis.
      CONCLUSION: The present consensus supports the use of topical antibiotics for
      bacterial conjunctivitis. Topical antibiotics shorten the course of the disease,
      reduce discomfort, prevent person-to-person transmission and reduce the rate of
      reinfection.

PMID- 29380708
TI  - Technology of RNA Interference in Advanced Medicine.
AB  - BACKGROUND: RNA interference (RNAi) and related pathways involving small
      interfering RNAs (siRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs)
      regulate processes such as antiviral defense, genome surveillance,
      heterochromatin formation, and gene expression in animals, plants, and fungi.
      Studies on RNAi have revealed a two-step mechanism: (i) Degradation of dsRNA into
      small interfering RNAs (siRNAs), 21 to 25 nucleotides long, by an RNase III-like
      activity. (ii) The siRNAs join an RNase complex, RISC (RNA-induced silencing
      complex), which acts on the mRNA and degrades it. OBJECTIVE: Molecular structures
      of Dicer, Argonaute proteins, and RNA-bound complexes have offered insights into
      the underlying mechanisms of RNA-silencing pathways. METHODS: Sequence specific
      gene silencing using small interfering RNA (siRNA) is now being evaluated as a
      novel therapeutic strategy. RESULTS: Recently, promising data have been obtained
      from clinical trials for the treatment of respiratory syncytial virus and age
      related macular degeneration. The exact mechanism of the RNAi pathways is still
      unclear. CONCLUSION: Our review summarizes the RNAi pathways and the known
      functions of siRNAs, miRNAs, and piRNAs in lower and higher organisms (mostly
      focusing on mammals) and discusses the potential applications of RNAi.

PMID- 29380709
TI  - Formulation and Evaluation of Niosomal in situ Nasal Gel of a Serotonin Receptor
      Agonist, Buspirone Hydrochloride for the Brain Delivery via Intranasal Route.
AB  - BACKGROUND: Buspirone Hydrochloride is an anxiolytic agent and serotonin receptor
      agonist belonging to azaspirodecanedione class of compounds used in the treatment
      of anxiety disorders. It has short half-life (2-3h) and low oral bioavailability
      (4%) due to extensive first pass metabolism. OBJECTIVE: The nasal mucosa has
      several advantages viz., large surface area, porous endothelial membrane, high
      blood flow, avoidance of first-pass metabolism and ready accessibility that lead
      to faster and higher drug absorption. Keeping these facts in mind, the objective
      of the present study was to develop Buspirone hydrochloride loaded niosomal in
      situ nasal gel. METHODS: Buspirone hydrochloride niosomal in situ nasal gel was
      formulated, optimized and evaluated with the objective to deliver drug to the
      brain via intranasal route. Niosomes were prepared by thin film evaporation
      method and optimized using32 factorial design. Niosomes were characterized for
      particle size, zeta potential, entrapment efficiency and in vitro drug release.
      Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol
      934P and HPMC K4M liquid gelling system for the formation of in situ gel. The
      resultant solution was assessed for various parameters, viz., gelling time,
      gelling capacity, viscosity at pH 5 and pH 6. RESULTS: The vesicle size of all
      niosomal suspension batches ranges between 168.3 -310.5 nm. The vesicle size of
      optimized niosomal suspension F5 batch is 181.9+/-0.36nm. For F5 batch, the value
      of zeta potential was found to be -15.4 mV; this specifies that prepared niosomes
      have sufficient surface charge to prevent aggregation of the vesicles. %
      entrapment efficiency for all batches was found in the range 72.44+/-0.18% to
      87.7+/-0.66%. The cumulative percent release of niosomal suspension ranges from
      66.34+/-0.39 to 84.26+/-0.26%. Ex vivo permeation of Buspirone hydrochloride
      through the sheep nasal mucosa showed that 83.49% w/w drug permeated after 8 h.
      The SEM and Zeta potential studies showed the formation of stable vesicles.
      CONCLUSION: Thus, the application of niosomes proved the potential for intranasal
      delivery of Buspirone hydrochloride over the conventional gel formulations.
      Overall intranasal drug delivery for Buspirone hydrochloride has been
      successfully developed.

PMID- 29380710
TI  - Spirituality, social support, and flexibility among older adults: a five-year
      longitudinal study.
AB  - OBJECTIVES: The objectives of the study were to examine the trajectory of
      spirituality among older adults, to investigate the roles of gender and religion
      on the developmental trajectory of spirituality, and to explore whether the
      linear growth of spirituality accelerated or decelerated at time points at which
      the participants reported high scores of social support and flexibility. DESIGN:
      A five-year longitudinal study. SETTING: The research used data from a
      longitudinal study, which follows a non-institutionalized older adults cohort of
      residents from France. The data used in this paper were collected at three time
      points (T1: 2007; T2: 2009; T3: 2012). PARTICIPANTS: A total of 567 participants
      were included in the analysis (59.44% female; M age = 75.90, SD = 5.12).
      MEASUREMENTS: Multilevel growth curve analysis was used measuring spirituality,
      satisfaction with social support, and flexibility. RESULTS: The results indicated
      the following: (1) stability of spirituality over time, (2) older women reported
      higher levels of spirituality than older men, and those who had a religion
      reported higher scores of spirituality than their counterparts who had no
      religion (these effects were strong and clinically meaningful), (3) older adults
      who reported higher levels of social support and flexibility also reported higher
      levels of spirituality, and (4) the slope of spirituality seemed to accelerate at
      time points at which participants also had higher levels of social support and
      flexibility (these effects were rather small but of theoretical interest).
      CONCLUSION: The results of the present study help to improve the understanding of
      the potential benefit of encouraging the spiritual aspects of life.

PMID- 29380711
TI  - A Simple Method for the Cross-Section Area Determination of Single Profiled
      Fibers and Its Application.
AB  - One of the critical prerequisites for accurately measuring the mechanical
      properties of profiled fibers is the precise determination of their cross
      sectional areas (CSAs). In this study, a new method is established for
      determining a single profiled fibers' CSA based on the frozen section method and
      digital photo, pixel-ratio method (FS-DP). FS-DP is used to obtain a transverse
      section of a fiber, by acquiring an image of the cross section using optical
      microscopy or scanning electron microscopy, and then calculating the CSA using
      Photoshop. Using FS-DP, it was found that the shape of a fiber of silk changes
      little in a range of 50 MUm, but varies considerably over a range of 1 m, while
      the CSA of cocoon silk (900 m) first increases and then decreases. Mechanical
      property tests showed that the elongation, strength, elastic modulus, and
      toughness values of the cocoon silk are consistent with those reported
      previously. Additionally, FS-DP was also used to observe other profiled fibers.
      The application tests indicated that FS-DP can be used to quickly and accurately
      obtain the CSA of a single profiled fiber, and that it is suitable for the large
      scale determination and analysis of the mechanical properties of profiled fibers.

PMID- 29380712
TI  - History of intranasal splints.
AB  - OBJECTIVE: Intranasal splints have long been utilised as a post-operative adjunct
      in septoplasty, intended to reduce the risk of adhesions and haematoma formation,
      and to maintain alignment during healing. METHODS: A Medline literature review of
      the history and evolution of intranasal splint materials and designs was
      performed. Advantages and disadvantages of various splints are discussed.
      RESULTS: Intranasal splints fashioned from X-ray film were first reported in
      1955. Since then, a variety of materials have been utilised, including
      polyethylene coffee cup lids, samarium cobalt magnets and dental utility wax.
      Most contemporary splints are produced from silicon rubber or
      polytetrafluoroethylene (Teflon). Designs have varied in thickness, flexibility,
      shape, absorption and the inclusion of built-in airway tubes. Future directions
      in splint materials and designs are discussed. CONCLUSION: Intranasal splints
      have steadily evolved since 1955, with numerous novel innovations. Despite their
      simplicity, they play an important role in nasal surgery and will continue to
      evolve over time.

PMID- 29380713
TI  - A pharmacopsychometric overview of major depressive episodes in positive
      psychiatry.
AB  - : ABSTRACTBackground:The use of the pharmacopsychometric triangle to enhance
      patient-reported well-being as the ultimate goal of treatment has most
      intensively been studied in patients with a major depressive episode. METHODS:
      The review is structured on the pharmacopsychometric triangle in which the
      desired clinical effect of an antidepressive medication is balanced against the
      undesired side effects induced by this medication in terms of restored well
      being. As a biological treatment, the antidepressive medication is compared
      clinically with both electroconvulsive therapy and psychological treatment.
      RESULTS: In the process of this review, evidence from a dose-response study in
      patients suffering from a major depressive episode with an adequate duration and
      symptom severity has demonstrated that the dose-response relationship emerged
      when using the patient-reported well-being outcome rather than the symptomatic
      reduction as outcome. CONCLUSION: The pharmacopsychometric triangle is in
      patients with major depressive episodes providing important information within
      positive psychiatry.

PMID- 29380714
TI  - Osteoporosis guideline awareness among Iranian family physicians: results of a
      knowledge, attitudes, and practices survey.
AB  - : AimThis study investigates the knowledge, attitudes, and practices (KAP) of
      family physicians in Iran, regarding osteoporosis and their experience with
      national osteoporosis guideline. BACKGROUND: Osteoporosis is a relatively
      preventable, chronic and progressive disease. Family physicians play a crucial
      role in relieving the burden of care. METHODS: This cross-sectional study was
      addressed at all qualified family physicians who registered at urban family
      physicians and referral system program. Data collection included demographics,
      professional experience, and knowledge of guidelines based on a standardized KAP
      questionnaire. Student's t-test was used to measure the associations between KAP
      scores and demographic, professional experience variables.FindingsThe response
      rate was 72% (540/750). Based on Bloom's cut off scale, family physicians
      knowledge and practice scores were in moderate level, and only 14 and 38.5% of
      them had good knowledge and practice, respectively. Attitude score was in good
      level, and 64.1% of participants had positive attitude. Mean score of knowledge
      and practice were higher significantly among family physicians that practice in
      public settings. Family physicians, who completed osteoporosis training courses,
      had higher attitude score (P=0.03). Only 23.5% of family physicians were aware of
      the existence of national osteoporosis guideline. CONCLUSION: Although most
      family physicians believed in the importance of preventive measures, however,
      limited number of them had good knowledge and practice regarding osteoporosis and
      less than a quarter were aware of national guideline. This is a clear need to
      disseminate the guideline more effectively, make greater use of efficient
      training methods.

PMID- 29380715
TI  - The need to support caregivers during pediatric bone marrow transplantation
      (BMT): A case report.
AB  - : ABSTRACTObjective:Pediatric bone marrow transplants represent a medically
      stressful, potentially traumatic experience for children and caregivers, and
      psychological support for parental caregivers is paramount to their long-term
      well-being. However, many medical centers do not have protocols in place to
      sustain caregiver well-being during these distressing experiences. METHOD: We
      report on a case of a 10-month-old infant with Wiskott Aldrich Syndrome who was
      hospitalized for bone marrow transplantation. RESULT: We describe the significant
      burden that fell upon caregivers during and after a bone marrow transplantation.
      SIGNIFICANCE OF RESULTS: This case helped guide our suggestions to improve care
      for caregivers. Several logistical hurdles could be overcome to alleviate some of
      these burdens. We suggest that a child psychologist or psychiatrist should be on
      patient care teams and be attentive to parental stress, impairments, or
      impediments to self-care, and signs of emergency of mental illness in this
      setting of medical trauma. Additionally, promotion of sleep hygiene and linkage
      to support systems can maximize resiliency. Finally, we believe that hospital
      administrators should partner with clinicians to facilitate routine support
      during highly stressful transitions of care.

PMID- 29380716
TI  - Spatiotemporal heterogeneity of malnutrition indicators in children under 5 years
      of age in Bangladesh, 1999-2011.
AB  - OBJECTIVE: To examine changes in the spatial clustering of malnutrition in
      children under 5 years of age (under-5s) for the period 1999 to 2011 in
      Bangladesh. DESIGN: We used data from four nationally representative Demographic
      and Health Surveys (DHS) conducted in 1999-2000, 2004, 2007 and 2011 in
      Bangladesh involving a total of 24 211 under-5s located in 1661 primary sampling
      units (PSU; geographical unit of analysis) throughout Bangladesh. The prevalence
      of stunting (height/length-for-age Z-score <-2), underweight (weight-for-age Z
      score <-2) and wasting (weight-for-height/length Z-score <-2) at each PSU site
      and for each survey year were estimated based on the WHO child growth standard.
      The extent of spatial clustering was quantified using semivariograms. SETTING:
      Whole of Bangladesh. SUBJECTS: Children under 5 years of age. RESULTS: Our
      results demonstrate that in 1999-2000 most PSU throughout Bangladesh experienced
      stunting, underweight and wasting prevalence which exceeded the WHO thresholds.
      By 2011, this situation improved, although in two of the six divisions (Barisal
      and Sylhet) PSU still exhibited higher levels of malnutrition compared with other
      divisions of the country. The pattern of spatial clustering for stunting,
      underweight and wasting also changed between 1999 and 2011 both at national and
      sub-national (division) levels. CONCLUSIONS: We identified divisions where
      malnutrition indicators (stunting, underweight and wasting) remain highly
      clustered and other divisions where they are more widely spread in Bangladesh.
      This has important implications on how interventions for malnutrition need to be
      delivered (geographically targeted interventions v. random interventions) within
      each division of the country.

PMID- 29380717
TI  - The Mediterranean diet, an environmentally friendly option: evidence from the
      Seguimiento Universidad de Navarra (SUN) cohort.
AB  - OBJECTIVE: How food is produced and consumed has consequences for ecosystems,
      such as resource use and greenhouse gas (GHG) emission among others. The
      Mediterranean diet (MedDiet) was proposed as a sustainable dietary model, due to
      its nutritional, environmental, economic and sociocultural dimensions. However,
      further evidence is needed. Thus, our objective was to evaluate the impact on
      resource (land, water and energy) use and GHG emission of better adherence to the
      MedDiet in a Mediterranean Spanish cohort. DESIGN: We analysed the dietary
      pattern of participants through a validated FFQ. The outcomes were land use,
      water and energy consumption and GHG emission according to MedDiet adherence. The
      specific environmental footprints of food item production and processing were
      obtained from different available life-cycle assessments. SETTING: Spanish
      university graduates. SUBJECTS: Participants (n 20 363) in the Seguimiento
      Universidad de Navarra (SUN) cohort. RESULTS: Better adherence to the MedDiet was
      associated with lower land use (-0.71 (95 % CI -0.76, -0.66) m2/d), water
      consumption (-58.88 (95 % CI -90.12, -27.64) litres/d), energy consumption (-0.86
      (95 % CI -1.01, -0.70) MJ/d) and GHG emission (-0.73 (95 % CI -0.78, -0.69) kg
      CO2e/d). A statistically significant linear trend (P<0.05) was observed in all
      these analyses. CONCLUSIONS: In this Mediterranean cohort, better adherence to
      the MedDiet was an eco-friendly option according to resource consumption and GHG
      emission.

PMID- 29380718
TI  - Antidepressant switching patterns in the elderly.
AB  - : ABSTRACTBackground:Switching between antidepressants is complex due to
      potential adverse outcomes such as serotonin syndrome and antidepressant
      discontinuation syndrome, yet switching is often required due to non-response to
      initial treatment. This study aimed to examine the patterns and extent of
      antidepressant switching in a cohort of older adults in long-term residential
      care. METHODS: A cohort study of medication supply data from 6011 aged care
      residents in 60 long-term care facilities was conducted. Incident antidepressant
      users were followed for 12 months and their patterns of antidepressant use
      determined. The type of switching from and to different antidepressant classes
      was determined according to National and International recommendations for
      antidepressant switching. RESULTS: In total, 11% (n = 44) of the residents were
      initiated on an antidepressant medication (n = 402) switched to a different
      antidepressant agent within 12 months. Residents commenced on a SNRI or TCA were
      most likely to switch antidepressants (17% in each group). Almost half of the
      switches (n = 21, 48% of all switches) were not implemented according to
      guideline recommendations. Direct switch and taper followed by wash out and
      switch, accounted for all of the inappropriate switching (29% and 71%,
      respectfully), with half occurring to mirtazapine (N = 7) or from mirtazapine (N
      = 3). CONCLUSIONS: Over one in 10 long-term aged care residents who commence an
      antidepressant will switch to a different antidepressant within 12 months.
      Current antidepressant switching practices in long-term residential aged care may
      be increasing the risk of harm associated with antidepressant switching, with
      around half of all switches not following current guideline recommendations.

PMID- 29380719
TI  - Impact of diabetes on caregiver stress in patients with Alzheimer's disease: data
      from the ICTUS study.
AB  - : ABSTRACTBackground:To estimate the impact of comorbid diabetes on caregiver
      stress in Alzheimer's disease (AD) patients from the Impact of Cholinergic
      Treatment Use (ICTUS) study. METHODS: Using the Data from the ICTUS study,
      diabetes mellitus (DM) was recorded at baseline and caregiver burden was assessed
      twice per year using the Zarit Burden Interview (ZBI) scale. The three-factorial
      model of ZBI (the effect on the social and personal life of caregivers, the
      psychological burden and the feelings of guilt) was adopted. Linear mixed models
      were used to examine the relation between DM and the scores of ZBI. RESULTS: The
      present analyses were conducted on 1,264 AD subjects. A total of 156 patients
      (12.3%) had DM with taking antidiabetic medication and/or self-report of a
      history. At baseline, the caregivers of patients with or without DM had similar
      ZBI global scores and similar scores of three different factors of ZBI.
      Unadjusted and adjusted models both indicated that ZBI global score increased
      over a 24-month follow-up without significant effect of DM. Similarly, unadjusted
      model showed that DM was not determining any significant difference in the score
      of any factor. However, adjusted model indicated that in diabetic patients, the
      scores of the social and personal life of caregivers and the psychological burden
      increased more slowly than those in non-diabetic patients (p = 0.04 and 0.01,
      respectively). CONCLUSIONS: DM may affect the caregivers' daily social and
      personal life and psychological burden in AD patients. It is necessary for
      further research.

PMID- 29380720
TI  - Risk factors of geriatric depression in rural China based on a generalized
      estimating equation.
AB  - : ABSTRACTBackground:The number of elderly individuals living in China is
      increasing rapidly. The aim of this study was to examine the potential risk
      factors of geriatric depression in rural areas. METHODS: A repeated cross
      sectional study was conducted between January 2015 and October 2016 in rural
      China. Nine hundred forty-five elderly individuals were included in both
      investigations. A generalized estimating equation (GEE) was used to examine the
      relationships between geriatric depression and socio-demographics, the number of
      chronic diseases, ADL (Activity of Daily Living) disability, cognitive
      impairment, and anxiety. RESULTS: Among the participants, the majority was female
      (61.4%) and illiterate (81.5%) and had a general economic status (63.0%) and more
      than two kinds of chronic diseases (62.9%). The bivariate analysis indicated that
      geriatric depression was associated with social support, education level,
      economic status, ADL disability, anxiety disorders, and cognitive impairment at
      both survey time points. The GEE results showed that poor economic status (OR =
      8.294, p < 0.001), the presence of more than two chronic diseases (OR = 1.681, p
      = 0.048), ADL disability (OR = 2.184, p < 0.001), cognitive impairment (OR =
      1.921, p < 0.001), and anxiety (OR = 5.434, p < 0.001) were risk factors for
      geriatric depression in rural China; better social support (OR = 0.924, 95% CI =
      0.899-0.949, p < 0.001) was found to be a protective factor. CONCLUSIONS:
      Geriatric depression in rural China was associated with several socio
      demographic, physical, and mental factors. Targeted interventions are essential
      to improve the psychological health of aged individuals in rural China.

PMID- 29380721
TI  - ASSOCIATION BETWEEN HIV AWARENESS FACTORS, HEALTH FACILITY CHARACTERISTICS AND
      RISKY SEXUAL BEHAVIOUR AMONG YOUNG WOMEN IN ZOMBA DISTRICT, MALAWI.
AB  - The objective of this study was to examine the association between multilevel
      factors related to HIV awareness and risky sexual behaviour among young women in
      Zomba district, Malawi. Secondary analyses of the Schooling, Income, and Health
      Risk (SIHR) study were undertaken. Four outcomes related to risky sexual
      behaviour were examined among young women: if participants had ever had sex,
      consistent condom use and two scores measuring risk related to partner history
      and age during sexual activity. Independent variables included individual-level
      factors such as education and rural/urban residence, as well as higher-level
      factors such as household's highest level of education and health facility
      characteristics. Regression models with cluster-robust standard errors and
      multilevel regression models were used to estimate associations; analyses were
      stratified into two strata by school enrolment status, i.e. whether the women
      were in school (N=1407) or had dropped out of school (N=407) at baseline of the
      SIHR study. For both strata, increasing age and residing within 16 km of an urban
      centre ('near rural' residence) increased the odds of ever having sex; lower
      educational achievement was associated with lower age during sexual activity. A
      history of pregnancy was associated with lower odds of condom use and riskier
      partner history. For women in school at baseline, lower household education was
      associated with higher odds of ever having sex (OR=1.48; 95% CI: 1.06, 2.07);
      near-rural and far-rural (<=16 km and >16km from urban centre, respectively)
      residence were associated with decreased odds of condom use (OR=0.47; 95% CI:
      0.28, 0.78; and OR=0.27; 95% CI: 0.11, 0.65, respectively). For those not in
      school at baseline, lower household education was associated with lower age
      during sexual activity (beta=0.31, 95% CI: 0.05, 0.58). Also for women not in
      school, the use of private or non-governmental health facilities was associated
      with decreased odds of condom use (OR=0.51, 95% CI: 0.39, 0.67) and higher age
      during sexual activity (beta=-0.30, 95% CI: -0.52, -0.09). While individual
      factors were associated with risky sexual behaviour in both strata, contextual
      factors differed.

PMID- 29380722
TI  - Sickness absence: a systematic review and meta-analysis of psychological
      treatments for individuals on sick leave due to common mental disorders.
AB  - Sick leave due to common mental disorders (CMDs) increase rapidly and present a
      major societal challenge. The overall effect of psychological interventions to
      reduce sick leave and symptoms has not been sufficiently investigated and there
      is a need for a systematic review and meta-analysis of the field. The aim of the
      present meta-analysis was to calculate the effect size of psychological
      interventions for CMDs on sick leave and psychiatric symptoms based on all
      published randomized controlled trials. Methodological quality, the risk of bias
      and publication bias were also assessed. The literature searches gave 2240 hits
      and 45 studies were included. The psychological interventions were more effective
      than care as usual on both reduced sick leave (g = 0.15) and symptoms (g = 0.21).
      There was no significant difference in effect between work focused interventions,
      problem-solving therapy, cognitive behavioural therapy or collaborative care. We
      conclude that psychological interventions are more effective than care as usual
      to reduce sick leave and symptoms but the effect sizes are small. More research
      is needed on psychological interventions that evaluate effects on sick leave.
      Consensual measures of sick leave should be established and quality of
      psychotherapy for patients on sick leave should be improved.

PMID- 29380723
TI  - "It's Like a Phantom Disease": Patient Perspectives on Access to Treatment for
      Chagas Disease in the United States.
AB  - Chagas disease (CD) affects > 6 million people globally, including > 300,000 in
      the United States. Although early detection and etiological treatment prevents
      chronic complications from CD, < 1% of U.S. cases have been diagnosed and
      treated. This study explores access to etiological treatment from the perspective
      of patients with CD. In semi-structured interviews with 50 Latin American-born
      patients of the Center of Excellence for Chagas Disease at the Olive View-UCLA
      Medical Center, we collected demographic information and asked patients about
      their experiences managing the disease and accessing treatment. Patients were
      highly marginalized, with 63.4% living below the U.S. poverty line, 60% lacking a
      high school education, and only 12% with private insurance coverage. The main
      barriers to accessing health care for CD were lack of providers, precarious
      insurance coverage, low provider awareness, transportation difficulties, and
      limited time off. Increasing access to diagnosis and treatment will not only
      require a dramatic increase in provider and public education, but also
      development of programs which are financially, linguistically, politically, and
      geographically accessible to patients.

PMID- 29380724
TI  - Relationships among Common Illness Symptoms and the Protective Effect of
      Breastfeeding in Early Childhood in MAL-ED: An Eight-Country Cohort Study.
AB  - Children in low-income countries experience multiple illness symptoms in early
      childhood. Breastfeeding is protective against diarrhea and respiratory
      infections, and these illnesses are thought to be risk factors of one another,
      but these relationships have not been explored simultaneously. In the eight-site
      MAL-ED study, 1,731 infants were enrolled near birth and followed for 2 years. We
      collected symptoms and diet information through twice-weekly household visits.
      Poisson regression was used to determine if recent illness history was associated
      with incidence of diarrhea or acute lower respiratory infections (ALRI),
      accounting for exclusive breastfeeding. Recent diarrhea was associated with
      higher risk of incident diarrhea after the first 6 months of life (relative risk
      [RR] 1.10, 95% confidence interval [CI] 1.04, 1.16) and with higher risk of
      incident ALRI in the 3- to 5-month period (RR 1.23, 95% CI 1.03, 1.47). Fever was
      a consistent risk factor for both diarrhea and ALRI. Exclusive breastfeeding 0-6
      months was protective against diarrhea (0-2 months: RR 0.39, 95% CI 0.32, 0.49; 3
      5 months: RR 0.83, 95% CI 0.75, 0.93) and ALRI (3-5 months: RR 0.81, 95% CI 0.68,
      0.98). Children with recent illness who were exclusively breastfed were half as
      likely as those not exclusively breastfed to experience diarrhea in the first 3
      months of life. Recent illness was associated with greater risk of new illness,
      causing illnesses to cluster within children, indicating that specific illness
      prevention programs may have benefits for preventing other childhood illnesses.
      The results also underscore the importance of exclusive breastfeeding in the
      first 6 months of life for disease prevention.

PMID- 29380727
TI  - The need for collaborative research in transplantation medicine: illustrated by
      the immunosuppression conversion trials.

PMID- 29380726
TI  - Genetic background and therapeutic response in generalized pustular psoriasis
      patients treated with granulocyte and monocyte adsorption apheresis.

PMID- 29380725
TI  - Neuronal activity determines distinct gliotransmitter release from a single
      astrocyte.
AB  - Accumulating evidence indicates that astrocytes are actively involved in brain
      function by regulating synaptic activity and plasticity. Different
      gliotransmitters, such as glutamate, ATP, GABA or D-serine, released form
      astrocytes have been shown to induce different forms of synaptic regulation.
      However, whether a single astrocyte may release different gliotransmitters is
      unknown. Here we show that mouse hippocampal astrocytes activated by endogenous
      (neuron-released endocannabinoids or GABA) or exogenous (single astrocyte Ca2+
      uncaging) stimuli modulate putative single CA3-CA1 hippocampal synapses. The
      astrocyte-mediated synaptic modulation was biphasic and consisted of an initial
      glutamate-mediated potentiation followed by a purinergic-mediated depression of
      neurotransmitter release. The temporal dynamic properties of this biphasic
      synaptic regulation depended on the firing frequency and duration of the neuronal
      activity that stimulated astrocytes. Present results indicate that single
      astrocytes can decode neuronal activity and, in response, release distinct
      gliotransmitters to differentially regulate neurotransmission at putative single
      synapses.

PMID- 29380728
TI  - Conversion from tacrolimus to everolimus with complete and early glucocorticoid
      withdrawal after kidney transplantation: a randomised trial.
AB  - BACKGROUND: While conversion from cyclosporine to everolimus is well documented,
      conversion from tacrolimus has been poorly studied. In this randomised,
      controlled trial the safety and tolerability of switching from tacrolimus to
      everolimus with glucocorticoid withdrawal after living-donor kidney
      transplantation was studied. METHODS: A total of 194 patients were planned to be
      randomised 1:1 to either continue tacrolimus or to convert to everolimus at month
      3 after transplantation. At randomisation, all patients received tacrolimus,
      mycophenolate mofetil and prednisolone. Everolimus was started in a dose of 1.5
      mg twice daily, aiming for predose concentrations of 4-7 ng/ml. Prednisolone was
      gradually withdrawn in both groups. RESULTS: The trial was stopped prematurely
      after the inclusion of 60 patients. The interim analysis showed an unacceptably
      high rejection rate in the everolimus group as compared with the control group:
      30.0% vs. 6.7% (95% CI: 0.047-0.420; p = 0.045). An additional 8 patients stopped
      everolimus because of toxicity. At the end of follow-up (month 12) only 12 (40%)
      patients assigned to everolimus were still on the study drug. CONCLUSIONS:
      Conversion from tacrolimus to everolimusbased immunosuppression with withdrawal
      of prednisolone three months after kidney transplantation results in an
      unacceptably high risk of acute rejection and causes considerable toxicity. Based
      on our findings, such a switch strategy cannot be recommended.

PMID- 29380729
TI  - Addition of simethicone improves small bowel capsule endoscopy visualisation
      quality.
AB  - BACKGROUND: Small bowel capsule endoscopy (SBCE) is an important diagnostic tool
      for small-bowel diseases but its quality may be hampered by intraluminal gas.
      This study evaluated the added value of the anti-foaming agent, simethicone, to a
      bowel preparation with polyethylene glycol (PEG) on the quality of small bowel
      visualisation and its use in the Netherlands. METHODS: This was a retrospective,
      single-blind, cohort study. Patients in the PEG group only received PEG prior to
      SBCE. Patients in the PEG-S group ingested additional simethicone. Two
      investigators assessed the quality of small-bowel visualisation using a four
      point scale for 'intraluminal gas' and 'faecal contamination'. By means of a
      survey, the use of anti-foaming agents was assessed in a random sample of 16
      Dutch hospitals performing SBCE. RESULTS: The quality of small bowel
      visualisation in the PEG group (n = 33) was significantly more limited by
      intraluminal gas when compared with the PEG-S group (n = 31): proximal segment
      83.3% in PEG group vs. 18.5% in PEG-S group (p < 0.01), distal segment 66.7% vs.
      18.5% respectively (p < 0.01). No difference was observed in the amount of faecal
      contamination (proximal segment 80.0% PEG vs. 59.3% PEG-S, p = 0.2; distal
      segment 90.0% PEG vs. 85.2% PEG-S, p = 0.7), mean small bowel transit times (4.0
      PEG vs. 3.9 hours PEG-S, p = 0.7) and diagnostic yield (43.3% PEG vs. 22.2% PEG
      S, p = 0.16). Frequency of anti-foaming agent use in the Netherlands was low
      (3/16, 18.8%). CONCLUSION: Simethicone is of added value to a PEG bowel
      preparation in improving the quality of visualisation of the small bowel by
      reducing intraluminal gas. At present, the use of anti-foaming agents in SBCE
      preparation is not standard practice in the Netherlands.

PMID- 29380730
TI  - Hurry up, it's quiet in the emergency department.
AB  - INTRODUCTION: Emergency department (ED) crowding is a contemporary problem.
      Solutions are multiple, but often involve a lengthy implementation process and/or
      substantial funding. Therefore, it is important that in the meanwhile, we aim to
      identify simple strategies, focussing on optimising efficiency of the available
      resources, which can be adopted in the ED here and now. METHODS: We made a
      careful analysis of inflow, throughput and outflow data of all 24,823 patients
      visiting the ED of a large teaching hospital in the year 2015, and looked in more
      detail at the 10 days with the longest average throughput times. RESULTS: The
      average throughput time during the study period was 130 minutes. The time between
      inflow and outflow peaks was well beyond the average daily ED throughput time,
      indicating that the 'midday surge in patient arrivals could not be handled
      adequately by the ED system. For the 10 days with the longest average throughput
      times, we found a very distinctive pattern, with a backlog of patients building
      up in the morning hours when maximum bed capacity had not yet been reached. This
      backlog had consequences during a significant part of the day. CONCLUSION:
      Improved timing of internal efforts in the ED based on careful analysis of ED
      performance data should be an integral part of a system approach to prevent ED
      crowding.

PMID- 29380731
TI  - Glucarpidase treatment for methotrexate intoxication: a case report and review of
      the literature.
AB  - High-dose methotrexate (MTX) induced acute kidney injury can lead to sustained
      high systemic MTX levels and severe toxicity. A 39-year-old man with
      lymphoblastic T-cell lymphoma was admitted to our intensive care unit with
      elevated serum creatinine and prolonged high serum MTX levels. Standard
      supportive care was complemented by the addition of a relatively novel agent,
      glucarpidase, which rapidly lowered the extracellular levels of MTX. Several case
      series support this effect of glucarpidase, but no randomised controlled trial
      has been performed to show this leads to better outcome. Furthermore,
      glucarpidase might negatively affect leucovorin rescue therapy. Lastly,
      glucarpidase carries a significant financial burden. Based on the current
      evidence we cannot recommend glucarpidase until further research elucidates its
      role in the treatment of MTX toxicity. There is no randomised clinical evidence
      to support its use in severe cases and theoretical evidence suggests that after
      prolonged exposure to high MTX levels glucarpidase administration is unable to
      reverse high intracellular MTX. We recommend that new randomised controlled
      studies be aimed at early administration of glucarpidase in patients with high
      MTX levels shortly after administration to prevent direct toxic effects of MTX on
      kidney function and further uptake into cells.

PMID- 29380733
TI  - Pancytopenia in a young girl with skin lesions.

PMID- 29380732
TI  - Fulminant presentation of oral mucosal leishmaniasis as severe stomatitis and
      periodontitis.
AB  - This case report shows an atypical presentation of mucosal leishmaniasis infantum
      in the oral cavity resulting in severe stomatitis and periodontitis. The patient
      was immunocompromised because of rheumatoid arthritis for which he used
      prednisone and methotrexate. He was treated with intravenous liposomal
      amphotericin B and recovered within four weeks.

PMID- 29380734
TI  - Answer to Photo Quiz: Pancytopenia in a young girl with skin lesions.

PMID- 29380735
TI  - From dentist to internist.

PMID- 29380736
TI  - Answer to Photo Quiz: From dentist to internist.

PMID- 29380738
TI  - Answer to Photo Quiz: Fever, abdominal erythema and subcutaneous emphysema.

PMID- 29380737
TI  - Fever, abdominal erythema and subcutaneous emphysema.

PMID- 29380739
TI  - Management of community-acquired pneumonia in adults: 2016 guideline update from
      the Dutch Working Party on Antibiotic Policy (SWAB) and Dutch Association of
      Chest Physicians (NVALT).
AB  - The Dutch Working Party on Antibiotic Policy in collaboration with the Dutch
      Association of Chest Physicians, the Dutch Society for Intensive Care and the
      Dutch College of General Practitioners have updated their evidence-based
      guidelines on the diagnosis and treatment of community-acquired pneumonia (CAP)
      in adults who present to the hospital. This 2016 update focuses on new data on
      the aetiological and radiological diagnosis of CAP, severity classification
      methods, initial antibiotic treatment in patients with severe CAP and the role of
      adjunctive corticosteroids. Other parts overlap with the 2011 guideline. Apart
      from the Q fever outbreak in the Netherlands (2007-2010) no other shifts in the
      most common causative agents of CAP or in their resistance patterns were observed
      in the last five years. Low-dose CT scanning may ultimately replace the
      conventional chest X-ray; however, at present, there is insufficient evidence to
      advocate the use of CT scanning as the new standard in patients evaluated for
      CAP. A pneumococcal urine antigen test is now recommended for all patients
      presenting with severe CAP; a positive test result can help streamline therapy
      once clinical stability has been reached and no other pathogens have been
      detected. Coverage for atypical microorganisms is no longer recommended in
      empirical treatment of severe CAP in the non-intensive care setting. For these
      patients (with CURB-65 score >2 or Pneumonia Severity Index score of 5) empirical
      therapy with a 2nd/3rd generation cephalosporin is recommended, because of the
      relatively high incidence of Gram-negative bacteria, and to a lesser extent S.
      aureus. Corticosteroids are not recommended as adjunctive therapy for CAP.

PMID- 29380740
TI  - Determination of Debye Temperatures and Lamb-Mossbauer Factors for
      LnFeO<sub>3</sub> Orthoferrite Perovskites (Ln = La, Nd, Sm, Eu, Gd).
AB  - Lanthanide orthoferrites have wide-ranging industrial uses including solar,
      catalytic and electronic applications. Here a series of lanthanide orthoferrite
      perovskites, LnFeO<sub>3</sub> (Ln = La; Nd; Sm; Eu; Gd), prepared through a
      standard stoichiometric wet ball milling route using oxide precursors, has been
      studied. Characterisation through X-ray diffraction and X-ray fluorescence
      confirmed the synthesis of phase-pure or near-pure LnFeO<sub>3</sub> compounds.
      <sup>57</sub>Fe Mossbauer spectroscopy was performed over a temperature range of
      10 K to 293 K to observe hyperfine structure and to enable calculation of the
      recoil-free fraction and Debye temperature (thetaD) of each orthoferrite. Debye
      temperatures (Ln = La 474 K; Nd 459 K; Sm 457 K; Eu 452 K; Gd 473 K) and recoil
      free fractions (Ln = La 0.827; Nd 0.817; Sm 0.816; Eu 0.812; Gd 0.826) were
      approximated through minimising the difference in the temperature dependent
      experimental Centre Shift (CS) and theoretical Isomer Shift (IS), by allowing the
      Debye temperature and Isomer Shift values to vary. This method of minimising the
      difference between theoretical and actual values yields Debye temperatures
      consistent with results from other studies determined through thermal analysis
      methods. This displays the ability of variable-temperature Mossbauer spectroscopy
      to approximate Debye temperatures and recoil-free fractions, whilst observing
      temperature induced transitions over the temperature range observed. X-ray
      diffraction and Rietveld refinement show an inverse relationship between FeO6
      octahedral volume and approximated Debye temperatures. Raman spectroscopy show an
      increase in the band positions attributed to soft modes of Ag symmetry,
      A<sub>g</sub>(3) and A<sub>g</sub>(5) from La to GdFeO<sub>3</sub> corresponding
      to octahedral rotations and tilts in the [010] and [101] planes respectively.

PMID- 29380741
TI  - Pass-band reconfigurable spoof surface plasmon polaritons.
AB  - In this paper, we introduce a new scheme to construct the band-pass tunable
      filter based on the band-pass reconfigurable spoof surface plasmon polaritons
      (SPPs), whose cut-off frequencies at both sides of the passband can be tuned
      through changing the direct current (DC) bias of varactors. Compared to
      traditional technology (e.g. microstrip filters), the spoof SPP structure can
      provide more tight field confinement and more significant field enhancement,
      which is extremely valuable for many system applications. In order to achieve
      this scheme, we proposed a specially designed SPP filter integrated with
      varactors and DC bias feeding structure to support the spoof SPP passband
      reconfiguration. Furthermore, the full-wave simulated result verifies the
      outstanding performance on both efficiency and reconfiguration, which has the
      potential to be widely used in advanced intelligent systems.

PMID- 29380742
TI  - Priming and cryopreservation of microencapsulated marrow stromal cells as a
      strategy for intervertebral disc regeneration.
AB  - A challenge in using stromal cells for intervertebral disc (IVD) regeneration is
      their limited differentiation capacity in vivo without exogenous growth factor
      (GF) supplementation. Priming of stromal cells prior to transplantation may offer
      a feasible strategy to overcome this limitation. Furthermore, the ability to
      cryopreserve cells could help alleviate logistical issues associated with storage
      and transport. With these critical translational challenges in mind, we aimed to
      develop a strategy involving priming and subsequent cryopreservation of
      microencapsulated bone marrow stromal cells (BMSCs). In phase one, we utilised
      the electrohydrodynamic atomisation process to fabricate BMSC-encapsulated
      microcapsules that were primed with TGF-beta3 for 14 d after which they were
      cultured for a further 21 d under basal or GF supplemented media conditions.
      Results showed that priming induced differentiation of BMSC microcapsules such
      that they synthesised significant amounts of sGAG (61.9 +/- 2.0 MUg and 55.3 +/-
      6.1 MUg for low and high cell densities) and collagen (24.4 +/- 1.9 MUg and 55.3
      +/- 4.6 MUg for low and high cell densities) in continued culture without GF
      supplementation compared to Unprimed microcapsules. Phase two of this work
      assessed the extracellular matrix forming capacity of Primed BMSC microcapsules
      over 21 d after cryopreservation. Notably, primed and cryopreserved BMSCs
      successfully retained the ability to synthesise both sGAG (24.8 +/- 2.7 MUg and
      75.1 +/- 11.6 MUg for low and high cell densities) and collagen (26.4 +/- 7.8 MUg
      and 93.1 +/- 10.2 MUg for low and high cell densities) post-cryopreservation.
      These findings demonstrate the significant potential of priming and
      cryopreservation approaches for IVD repair and could possibly open new horizons
      for pre-designed, 'off-the-shelf' injectable therapeutics.

PMID- 29380743
TI  - Radiation dose from percutaneous transluminal coronary angioplasty procedure
      performed using a flat detector for different clinical angiographic projections.
AB  - The radiation dose from complex cardiac procedures is of concern due to the
      lengthy fluoroscopic screening time and vessel complexities. This study intends
      to assess radiation dose based on angiographic projection and vessel complexities
      for clinical protocols used in the performance of percutaneous transluminal
      coronary angioplasty (PTCA). Dose-area product (DAP), reference air kerma (K a,r)
      and real-time monitoring of tube potentials and tube current for each
      angiographic projection and dose setting were evaluated for 66 patients who
      underwent PTCA using a flat detector system. The mean DAP and cumulative K a,r
      were 32.71 Gy cm2 (0.57 Gy), 51.24 Gy cm2 (0.9 Gy) and 102.03 Gy cm2 (1.77 Gy)
      for single-, double- and triple-vessel PTCA, respectively. Among commonly used
      angiographic projections, left anterior oblique 45 degrees -caudal 35 degrees 
      reached 2 Gy in 55 min using a low-dose fluoroscopy setting and 21 min for a
      medium-dose setting. Use of a low-dose setting for fluoroscopic screening showed
      a radiation dose reduction of 39% compared with a medium-dose setting.

PMID- 29380744
TI  - Automated EEG sleep staging in the term-age baby using a generative modelling
      approach.
AB  - OBJECTIVE: We develop a method for automated four-state sleep classification of
      preterm and term-born babies at term-age of 38-40 weeks postmenstrual age (the
      age since the last menstrual cycle of the mother) using multichannel
      electroencephalogram (EEG) recordings. At this critical age, EEG differentiates
      from broader quiet sleep (QS) and active sleep (AS) stages to four, more complex
      states, and the quality and timing of this differentiation is indicative of the
      level of brain development. However, existing methods for automated sleep
      classification remain focussed only on QS and AS sleep classification. APPROACH:
      EEG features were calculated from 16 EEG recordings, in 30 s epochs, and
      personalized feature scaling used to correct for some of the inter-recording
      variability, by standardizing each recording's feature data using its mean and
      standard deviation. Hidden Markov models (HMMs) and Gaussian mixture models
      (GMMs) were trained, with the HMM incorporating knowledge of the sleep state
      transition probabilities. Performance of the GMM and HMM (with and without
      scaling) were compared, and Cohen's kappa agreement calculated between the
      estimates and clinicians' visual labels. MAIN RESULTS: For four-state
      classification, the HMM proved superior to the GMM. With the inclusion of
      personalized feature scaling, mean kappa (+/-standard deviation) was 0.62 (+/
      0.16) compared to the GMM value of 0.55 (+/-0.15). Without feature scaling,
      kappas for the HMM and GMM dropped to 0.56 (+/-0.18) and 0.51 (+/-0.15),
      respectively. SIGNIFICANCE: This is the first study to present a successful
      method for the automated staging of four states in term-age sleep using
      multichannel EEG. Results suggested a benefit in incorporating transition
      information using an HMM, and correcting for inter-recording variability through
      personalized feature scaling. Determining the timing and quality of these states
      are indicative of developmental delays in both preterm and term-born babies that
      may lead to learning problems by school age.

PMID- 29380745
TI  - Thermo-solutal growth of an anisotropic dendrite with six-fold symmetry.
AB  - A stable growth of dendritic crystal with the six-fold crystalline anisotropy is
      analyzed in a binary nonisothermal mixture. A selection criterion representing a
      relationship between the dendrite tip velocity and its tip diameter is derived on
      the basis of morphological stability analysis and solvability theory. A complete
      set of nonlinear equations, consisting of the selection criterion and
      undercooling balance condition, which determines implicit dependencies of the
      dendrite tip velocity and tip diameter as functions of the total undercooling, is
      formulated. Exact analytical solutions of these nonlinear equations are found in
      a parametric form. Asymptotic solutions describing the crystal growth at small
      Peclet numbers are determined. Theoretical predictions are compared with
      experimental data obtained for ice dendrites growing in binary water
      ethylenglycol solutions as well as in pure water.

PMID- 29380746
TI  - Mathematical optimization of high dose-rate brachytherapy-derivation of a linear
      penalty model from a dose-volume model.
AB  - High dose-rate brachytherapy is a method for cancer treatment where the radiation
      source is placed within the body, inside or close to a tumour. For dose planning,
      mathematical optimization techniques are being used in practice and the most
      common approach is to use a linear model which penalizes deviations from
      specified dose limits for the tumour and for nearby organs. This linear penalty
      model is easy to solve, but its weakness lies in the poor correlation of its
      objective value and the dose-volume objectives that are used clinically to
      evaluate dose distributions. Furthermore, the model contains parameters that have
      no clear clinical interpretation. Another approach for dose planning is to solve
      mixed-integer optimization models with explicit dose-volume constraints which
      include parameters that directly correspond to dose-volume objectives, and which
      are therefore tangible. The two mentioned models take the overall goals for dose
      planning into account in fundamentally different ways. We show that there is,
      however, a mathematical relationship between them by deriving a linear penalty
      model from a dose-volume model. This relationship has not been established before
      and improves the understanding of the linear penalty model. In particular, the
      parameters of the linear penalty model can be interpreted as dual variables in
      the dose-volume model.

PMID- 29380747
TI  - Quantum anomalous Hall phase in a one-dimensional optical lattice.
AB  - We propose to simulate and detect quantum anomalous Hall phase with ultracold
      atoms in a one-dimensional optical lattice, with the other synthetic dimension
      being realized by modulating spin-orbit coupling. We show that the system
      manifests a topologically nontrivial phase with two chiral edge states which can
      be readily detected in this synthetic two-dimensional system. Moreover, it is
      interesting that at the phase transition point there is a flat energy band and
      this system can also be in a topologically nontrivial phase with two Fermi zero
      modes existing at the boundaries by considering the synthetic dimension as a
      modulated parameter. We also show how to measure these topological phases
      experimentally in ultracold atoms. Another model with a random Rashba and
      Dresselhaus spin-orbit coupling strength is also found to exhibit topological
      nontrivial phase, and the impact of the disorder to the system is revealed.

PMID- 29380748
TI  - Studies on the high-temperature ferroelectric transition of multiferroic
      hexagonal manganite RMnO3.
AB  - Hexagonal manganites are multiferroic materials with two highly-dissimilar phase
      transitions: a ferroelectric transition (from P63/mmc to P63cm) at a temperature
      higher than 1000 K and an antiferromagnetic transition at T N  =  65-130 K.
      Despite its critical relevance to the intriguing ferroelectric domain physics,
      the details of the ferroelectric transition are not well known to date primarily
      because of the ultra-high transition temperature. Using high-temperature x-ray
      diffraction experiments, we show that the ferroelectric transition is a single
      transition of abrupt order and R-Op displacement is the primary order parameter.
      This structural transition is then simultaneously accompanied by MnO5 tilting and
      the subsequent development of electric polarization.

PMID- 29380749
TI  - Injectable hydrogels of optimized acellular nerve for injection in the injured
      spinal cord.
AB  - OBJECTIVE: Spinal cord injury (SCI) affects a quarter million individuals in the
      United States, and there is currently no clinical treatment. Both fresh and
      acellular peripheral nerve grafts can induce spinal axon regeneration and support
      functional recovery in experimental injury models. Nonetheless, a scaffold that
      can be injected into a spinal contusion would be far less invasive to apply. We
      aimed to develop the first injectable acellular nerve graft for promoting repair
      after contusion SCI. APPROACH: We report a method to enzymatically solubilize
      optimized acellular (OA) nerve-a decellularized peripheral nerve graft developed
      in our laboratory and currently used clinically-to obtain an injectable solution
      that undergoes thermal gelation under physiological conditions. We quantified
      multiple physical and compositional properties of this novel material as well as
      tested its efficacy at acute and chronic time points following cervical contusion
      SCI. MAIN RESULTS: This injectable optimized acellular (iOA) nerve graft retains
      native chemical cues such as collagens and glycosaminoglycans. By varying
      hydrogel concentration, the rheological properties and compressive modulus of iOA
      were similar to that previous reported for rat central nervous tissue. iOA
      solution was compatible with rat Schwann cells in culture, and hydrogel injection
      into a rat cervical contusion model significantly reduced the ratio of M1:M2
      macrophages after one week, favoring regenerative phenotypes (p < 0.05).
      Furthermore, while iOA treatment did not affect locomotor or respiratory recovery
      over an eight week period, the percentage of axonal coverage increased at the
      distal tissue interface (p < 0.05), suggesting enhanced axonal extension within
      this region. SIGNIFICANCE: Our data indicate that this novel injectable form of
      acellular nerve grafts is amenable for use after contusion SCI and may bolster a
      simultaneous therapy by acutely modulating the inflammatory milieu and supporting
      axonal growth.

PMID- 29380750
TI  - 3D prompt gamma imaging for proton beam range verification.
AB  - We tested the ability of a single Compton camera (CC) to produce 3-dimensional
      (3D) images of prompt gammas (PGs) emitted during the irradiation of a tissue
      equivalent plastic phantom with proton pencil beams for clinical doses delivered
      at clinical dose rates. PG measurements were made with a small prototype CC
      placed at three different locations along the proton beam path. We evaluated the
      ability of the CC to produce images at each location for two clinical scenarios:
      (1) the delivery of a single 2 Gy pencil beam from a hypo-fractionated treatment
      (~9  *  108 protons), and (2) a single pencil beam from a standard treatment (~1 
      *  108 protons). Additionally, the data measured at each location were combined
      to simulate measurements with a larger scale, clinical CC and its ability to
      image shifts in the Bragg peak (BP) range for both clinical scenarios. With our
      prototype CC, the location of the distal end of the BP could be seen with the CC
      placed up to 4 cm proximal or distal to the BP distal falloff. Using the data
      from the simulated full scale clinical CC, 3D images of the PG emission were
      produced with the delivery of as few as 1  *  108 protons, and shifts in the
      proton beam range as small as 2 mm could be detected for delivery of a 2 Gy spot.
      From these results we conclude that 3D PG imaging for proton range verification
      under clinical beam delivery conditions is possible with a single CC.

PMID- 29380751
TI  - Efficacy of topical 5% fluorouracil needling in vitiligo.

PMID- 29380752
TI  - Solitary dome-shaped erythematous lump of long duration on the palm.

PMID- 29380753
TI  - Retinal vasoproliferative tumor - A proposal for classification.

PMID- 29380754
TI  - Diabetic retinopathy screening: Telemedicine, the way to go!

PMID- 29380755
TI  - Traumatic retrobulbar hemorrhage?

PMID- 29380756
TI  - Anatomy of cornea and ocular surface.
AB  - Important functions of cornea in the eye include protecting the structures inside
      the eye, contributing to the refractive power of the eye, and focusing light rays
      on the retina with minimum scatter and optical degradation. Considerable advances
      have taken place in understanding the organization of collagen in the corneal
      stroma and its clinical significance. In this review, the structure and function
      of various components of cornea and ocular surface are presented.

PMID- 29380757
TI  - Cornea and anterior eye assessment with slit lamp biomicroscopy, specular
      microscopy, confocal microscopy, and ultrasound biomicroscopy.
AB  - Current corneal assessment technologies make the process of corneal evaluation
      extremely fast and simple, and several devices and technologies show signs that
      help in identification of different diseases thereby, helping in diagnosis,
      management, and follow-up of patients. The purpose of this review is to present
      and update readers on the evaluation of cornea and ocular surface. This first
      part reviews a description of slit lamp biomicroscopy (SLB), endothelial specular
      microscopy, confocal microscopy, and ultrasound biomicroscopy examination
      techniques and the second part describes the corneal topography and tomography,
      providing up-to-date information on the clinical recommendations of these
      techniques in eye care practice. Although the SLB is a traditional technique, it
      is of paramount importance in clinical diagnosis and compulsory when an eye test
      is conducted in primary or specialist eye care practice. Different techniques
      allow the early diagnosis of many diseases, especially when clinical signs have
      not yet become apparent and visible with SLB. These techniques also allow for
      patient follow-up in several clinical conditions or diseases, facilitating
      clinical decisions and improving knowledge regarding the corneal anatomy.

PMID- 29380758
TI  - Clinical signs in cornea and ocular surface.
AB  - A careful examination of cornea and ocular surface eliciting the basic signs will
      help a clinician toward an accurate diagnosis. Flipping the upper lid or pulling
      the lower lid to look at the inferior fornix may help to pick up any subtle
      clinical sign. Meticulous documentation by diffuse and slit view will help in
      following up the disease. Eyelids and ocular surface are evaluated externally and
      by slit lamp. Slit-lamp examination with the use of the stains such as
      fluorescein, rose bengal, or lissamine green provides extensive knowledge about
      the ocular surface. Tests of tear production are also detailed herein. This
      review is intended to help the eye practitioners in eliciting common clinical
      signs seen in cornea and ocular surface diseases.

PMID- 29380759
TI  - Prevalence and risk factors of dry eye disease in North India: Ocular surface
      disease index-based cross-sectional hospital study.
AB  - PURPOSE: This study aims to study the prevalence of DED and analyze risk factors
      in North Indian population. METHODS: This was a cross-section hospital-based,
      observational study. Cases enrolled over 2 years (systematic random sampling)
      were administered ocular surface disease index questionnaire to evaluate the
      prevalence and risk factors of DED. Schirmer's test and tear break-up time were
      performed only in the subset of patients giving consent. Categorical data were
      assessed with Chi-square/Fisher's Exact test, and odds ratio was analyzed using
      bivariate and multivariate logistic regression. P < 0.05 was statistically
      significant. RESULTS: A total of 15,625 patients were screened. The prevalence of
      DED was 32% (5000/15625); 9.9% (496/5000) had mild DED; 61.2% (3060/5000) had
      moderate DED; and 28.9% (1444/5000) had severe DED. Age group of 21-40 years,
      male sex, urban region, and desk job were associated with increased risk of DED.
      Hours of visual display terminal (VDT) usage significantly correlated with DED (P
      < 0.001), and 89.98% of patients with 4 h or more of VDT use had severe dry eye.
      Cigarette smoking and contact lens usage had increased odds of developing severe
      DED (P < 0.001). Objective tests were undertaken in 552 patients; of these, 81.3%
      (449/552) had severe DED. CONCLUSIONS: The prevalence of DED in North India is
      32%, with the age group of 21-40 years affected most commonly. VDT use, smoking,
      and contact lens use were associated with increased odds of developing DED.

PMID- 29380760
TI  - Interface healing and its correlation with visual recovery and quality of vision
      following small incision lenticule extraction.
AB  - PURPOSE: To study the time course of interface healing and its correlation with
      visual acuity, modulation transfer function (MTF), and aberrations after myopic
      small-incision lenticule extraction (SMILE) correction. METHODS: Seventy-eight
      eyes of 78 patients (1 eye per patient) with a mean age of 25.7 years and mean
      spherical equivalent (SE) of -3.74D, undergoing bilateral SMILE procedure, were
      included in this study. On postoperative day 1, 2 weeks, and 3 months, dilated
      retroillumination photographs were taken and morphology of corneal interface was
      graded by comparing them with 5 standard templates representing 5 grades of
      interface roughness (IRG): IRG - 0 (clear), IRG - 1 (mild), IRG - 2 (moderate),
      IRG - 3 (severe), and IRG - 4 (severe IRG with Bowman's folds in visual axis).
      Pearson's correlations were computed to study correlation associations, and
      Wilcoxon signed-rank test was used for intragroup comparison of means. P <= 0.05
      was considered statistically significant. RESULTS: At 3 months, 90.70% eyes were
      Grade 0 while 9.30% eyes still had Grade 2 interface granularity. Mean IRG
      significantly improved from 2.47 +/- 0.57 at day 1 to 0.62 +/- 0.53 at 3 months
      (P = 0.00). At day 1, pre-SE showed a significant positive correlation with IRG;
      however, mean postoperative corrected distant visual acuity (CDVA, in decimal),
      corneal Strehl ratio (SR), and MTF showed weak but significant negative
      correlation with IRG (r2 = 0.28 for SE, -0.052 for CDVA, -0.017 for SR, and -0.39
      for MTF, respectively, P < 0.05 for all correlations). At 2 weeks and 3 months,
      corneal MTF continued to show a significant negative correlation, whereas other
      parameters did not show any correlation with IRG. CONCLUSION: Visual quality and
      corneal MTF may be significantly affected by the IRG in the immediate
      postoperative period after SMILE and may take 3 months or more for complete
      recovery.

PMID- 29380761
TI  - Effect of transfer of donor corneal tissue from McCarey-Kaufmann medium to
      Optisol-GS on corneal endothelium.
AB  - PURPOSE: The purpose of this study is to evaluate the effect of transfer of donor
      corneal tissue from McCarey-Kaufmann (MK) medium to Optisol-GS on corneal
      endothelium. METHODS: This was a prospective, randomized comparative study.
      Twenty paired human donor corneal tissues of optical quality were retrieved. One
      tissue of the pair was preserved in Optisol-GS preservative medium (Group A) and
      other tissue of the pair in MK medium (Group B) at the time of corneoscleral disc
      excision. Within 12 h of retrieval, each cornea was evaluated using slit-lamp
      biomicroscopic examination and specular microscopic analysis. Group B corneas
      were transferred to Optisol-GS medium within 48-53 h of retrieval. Specular
      analysis of the paired corneas was repeated 3 h after transferring to Optisol-GS.
      On day 7 of storage, specular analysis of both the tissues was repeated. RESULTS:
      The average age of the donor at the time of death was 29 years (16-68 years). The
      reduction in endothelial cell count, from baseline, in Groups A and B was 5.5%
      and 5.8% (P = 0.938) on the 3rd day and 8.2% and 12.6% (P = 0.025) on the 7th
      day, respectively, postretrieval. The coefficient of variation (CV) increased by
      36% (P = 0.021) and hexagonality reduced by 19% (P = 0.007) on day 7. All tissues
      retained an endothelial cell density higher than the accepted critical level for
      penetrating keratoplasty. CONCLUSION: Significant endothelial cell loss was noted
      while transferring tissues from one medium to another, necessitating the need for
      reevaluation of transferred tissues before utilization.

PMID- 29380762
TI  - Effect of transfer of donor corneal tissue from McCarey-Kaufman medium to Optisol
      on corneal endothelium.

PMID- 29380763
TI  - Application of polycaprolactone nanofibers as patch graft in ophthalmology.
AB  - PURPOSE: The purpose of the study was to evaluate tissue reaction to
      polycaprolactone (PCL) nanofiber patches in the cornea, conjunctiva, and anterior
      chamber (AC) in rabbit eyes and to assess their biocompatibility for use as patch
      grafts. METHODS: Two 100 MU PCL patches were implanted under the conjunctiva and
      in the corneal stroma of one albino New Zealand rabbit, and pathologic evaluation
      was done after 3 weeks. In the next step, two PCL patches were implanted; one in
      the corneal stroma and the other in the AC of two rabbits followed by pathologic
      evaluation after 3 months. RESULTS: On slit-lamp examination, there was minimum
      inflammation in all cases. Pathologic examination showed that the contact and
      probably merging between the host tissue and PCL fibers were achieved with
      minimal tissue reaction. CONCLUSION: As a biocompatible material, PCL nanofibers
      seem to be a promising modality for the repair of different tissue defects
      including melting, thinning, and perforation. They may also be a suitable
      material for manufacturing keratoprostheses.

PMID- 29380764
TI  - Identification of a novel frameshift mutation in PAX6 gene and the clinical
      management in an Asian Indian aniridia family.
AB  - PURPOSE: This study aimed to characterize an Asian Indian aniridia family for
      both the phenotype and genotype of the disease for a better clinical management.
      METHODS: The phenotype and genotype of the affected and unaffected individuals in
      the aniridia family were evaluated. The subjects underwent a standard ophthalmic
      evaluation followed by molecular screening of PAX6 gene in the peripheral blood
      for mutation detection. RESULTS: The three affected individuals had aniridia with
      several common features and an uncommon presentation of bilateral congenital
      ptosis. Two affected siblings, a brother and a sister, had aniridia, nystagmus,
      ptosis, increase in central corneal thickness, cataract, and foveal hypoplasia.
      The sister had features of glaucoma. The offspring of the sister had all the
      features except cataract and rise in intraocular pressure. Mutation screening of
      PAX6 gene helped in identifying a novel heterozygous pathogenic variation g.
      31801757dupG (c. 216-19dupG) that resulted in a frameshift mutation that extended
      into exon 7. Based on the evaluation and diagnostic testing, the family was
      clinically managed along with genetic counselling. CONCLUSION: Molecular
      diagnostic testing helps in genetic counseling of the family with aniridia to
      understand the nature of the disease and detection of complications early for
      better management.

PMID- 29380765
TI  - Analysis of yield of retinal imaging in a rural diabetes eye care model.
AB  - PURPOSE: The aim of this study is to analyze the yield of retinal images obtained
      in a rural diabetes eye care model. METHODS: An analysis of a sample of
      nonmydriatic fundus photography (NMFP) of posterior segment ophthalmic images,
      obtained by an indigenous equipment (3 nethra-Forus Royal), was done in a
      district-wide rural diabetic retinopathy (DR) screening program; a trained
      optometrist did the initial image grading. DR and diabetic macular edema (DME)
      were classified based on international DR and DME severity scale. The agreement
      between the optometrist and retina specialist was very good (kappa = 0.932;
      standard error = 0.030; 95% confidence interval = 0.874-0.991). RESULTS:
      Posterior segment images of 2000 eyes of 1000 people with diabetes mellitus (DM)
      were graded. The mean age of the participants was 55.7 +/- 11.5 standard
      deviation years. Nearly 42% of the screened participants (n = 420/1000) needed
      referral. The most common referable posterior segment abnormality was DR (8.2%).
      The proportion of people with any form of DR was seen in 110/1225 eyes, and sight
      threatening DR was seen in 35/1225 eyes. About 62% of posterior segment images
      were gradable. The reasons for ungradable posterior segment images (34%) were
      small pupil, unfocused/partially available field of images, and cataract.
      CONCLUSION: A NMFP model was able to detect referable posterior segment
      abnormalities in a rural diabetes eye care program. Reasons found for
      ungradability of images in the present study can be addressed while designing
      future DR screening programs in the rural areas.

PMID- 29380766
TI  - Transcleral approach for closing retinal tears using DuraSealTM hydrogel sealant.
AB  - PURPOSE: The aim of this study was to evaluate an innovative approach for closing
      retinal tears using DuraSealTM (DS) hydrogel sealant in a rabbit model. METHODS:
      Retinal detachment with a small tear was performed on 20 New Zealand rabbits.
      Thereafter, rabbits were divided into two groups; the experimental group received
      a transscleral injection of 0.1 ml DS into the subretinal space whereas the
      control group received sham injection of saline. Eyes were clinically evaluated
      using indirect ophthalmoscopy, retinal function was recorded in ten rabbits by
      electroretinography and the sealant's toxicity was evaluated histopathologically.
      RESULTS: We found that the DS hydrogel was easily injected transsclerally into
      the subretinal space of the detached retinas with no major complications. Retinal
      reattachment was seen in both groups within 2 weeks with no toxicity to the
      sensory retina. There were no significant differences in retinal function between
      groups. CONCLUSION: Subretinal injection of hydrogel through a transscleral route
      is easy to perform and may open a new avenue in the treatment of retinal
      detachment. However, the efficacy of the DS as a tamponade for sealing retinal
      tear is yet to be definite. Long-term clinical, functional, and toxicological
      studies are needed to evaluate its full potential for clinical applications.

PMID- 29380767
TI  - Diathermy to tissue adhesives for retinal tears: The future of retinal
      reattachment surgery.

PMID- 29380768
TI  - Clinical features and treatment outcomes of vasoproliferative tumors in Indian
      participants.
AB  - PURPOSE: The aim of the study was to describe the clinical features and treatment
      outcomes of vasoproliferative tumors (VPT) in Indian participants. METHODS: This
      study design was a retrospective case series in a tertiary eye care center. Case
      records of patients diagnosed with VPT from 2011 to 2015 were reviewed, and their
      demographic details, clinical presentation, and treatment outcomes were
      documented. Baseline and follow-up visual acuity and tumor dimensions were
      statistically compared by applying paired t-test. Statistical analysis used SPSS
      version 14. RESULTS: Twenty-two tumors from 19 eyes of 17 patients were included.
      Mean age at presentation was 43.5 years (range: 15-68 years). Mean presenting
      best-corrected visual acuity (BCVA) was + 1.10 logMAR. Sixty-eight percent eyes
      had secondary tumors. Most common association of secondary VPT was Coats disease
      followed by retinal vasculitis, polypoidal choroidal vasculopathy, familial
      exudative vitreoretinopathy, and traumatic chorioretinopathy. Ten tumors (45%)
      involved the inferior quadrant. Tumor-associated features were intra/subretinal
      exudates, vitritis, subretinal fluid, vitreous hemorrhage, preretinal fibrosis,
      epiretinal membrane, and subretinal blood. Treatment included cryotherapy,
      intravitreal or oral steroids, laser photocoagulation, cryotherapy with
      encirclage, cryotherapy with anti-vascular endothelial growth factor, and
      observation. Complications included tumor recurrence, retinal detachment, raised
      intraocular pressure, neovascularization of iris, and cataract. Ninety-five
      percent VPT regressed at mean 21 months (Median: 17 months; Range: 3-64 months).
      Mean final BCVA was + 1.21 logMAR. CONCLUSION: VPTs are commonly unilateral,
      unifocal, and located anterior to equator in inferior fundus. Secondary tumors
      are more common than primary tumors. Treatment achieves tumor regression in
      majority of cases.

PMID- 29380769
TI  - A study on the contamination of injection bevacizumab on storage of multidose
      vials.
AB  - PURPOSE: The aim of this study is to establish the safety of storage and reuse of
      bevacizumab vials for 1 week with multiple vial punctures. METHODS: This was an
      experimental microbiological study conducted at tertiary care hospital. The study
      samples included bevacizumab vials that had been used for injecting patients by
      the pooling method. Vials were stored and sampled in a manner that replicated
      their proposed clinical use. Contamination of vials was evaluated on the basis of
      microbial culture and validated by positive and negative controls. The
      probability of obtaining such results purely by chance was calculated. RESULTS: A
      total of 210 samples from 30 vials were evaluated along with 210 positive and 210
      negative controls. No growth was seen in any of the bevacizumab samples. The
      probability of obtaining 210 consecutive sterile samples just by chance is <5.547
      * 10-6 (0.000005547). CONCLUSION: The vials showed no contamination on storage
      for 7 days in an ordinary refrigerator. Thus, we conclude that the rate of
      contamination of bevacizumab vials on storage for 7 days in a refrigerator is
      likely to be insignificant. The results need to be validated by other studies
      replicating this protocol.

PMID- 29380770
TI  - A 3-year prospective study on ocular injuries with tennis or cricket ball while
      playing cricket: A case series.
AB  - PURPOSE: The purpose of this study is to study the clinical features, visual
      outcome, management, and ocular complications of ocular injury, following trauma
      with tennis or cricket ball. METHODS: A prospective, noncomparative case study of
      patients having injury with tennis/cricket ball while playing cricket was
      conducted between January 2013 and April 2016. Seventy-six eyes of 76 patients
      were studied. Presenting vision, age, gender, time since injury, general and
      ocular examination, intraocular pressure, indirect ophthalmoscopy, B scan, and X
      ray/computed tomography scan findings were noted. Patients were managed medically
      or surgically as per the need and followed up at least for 6 months. RESULTS:
      Seventy-six eyes of 76 patients were studied. All cases were male, except two.
      Majority (80.2%) were <25 years. Median presenting visual acuity (VA) was 6/36
      and median final VA was 6/18. Significant findings in the decreasing order of
      frequency were sphincter tear (26.3%), retinal detachment (23.6%), angle
      recession (18.4%), choroidal rupture (17.1%), and Berlin's edema (15.7%). Most of
      the cases (69.7%) were managed medically. Only 30.2% cases needed surgical
      intervention. Final visual outcome in our study was depended on initial VA (P =
      0.000). It was also correlating with presenting clinical feature (P = 0.010) and
      type of intervention (medical/surgical) (P = 0.001). CONCLUSION: Cricket-related
      ocular injury generally has a poor prognosis with most cases being closed globe
      injury; retinal detachment is the most common vision-threatening presentation. In
      spite of being a common event, cricket-related injury is sparingly documented and
      hence needs further studies for proper documentation, prognostication, and
      formulation of definitive management plan.

PMID- 29380772
TI  - Assessing the outcomes of mini-Monoka stent dilatation for primary punctal
      stenosis using the lacrimal symptom questionnaire.
AB  - PURPOSE: The objective of this study was to assess the quality of outcomes of
      mini-Monoka stent dilatation for punctal stenosis using the lacrimal symptom (Lac
      Q) questionnaire. METHODS: Prospective interventional case series of 45 eyes of
      25 consecutive patients who underwent mini-Monoka stent dilatation for primary
      punctal stenosis were included in the study. The stents were extubated at 4
      weeks. The Lac-Q questionnaire was administered preoperatively and at 12 weeks
      and 24 weeks following the intervention. Outcomes assessed were anatomical
      success, functional success, and changes in the questionnaire scores including
      total, social impact, and lacrimal symptom scores. Statistical analysis was
      performed using the Wilcoxon signed-rank test, and the probability of obtaining a
      certain score was calculated using the multinomial log-linear model. P < 0.05 was
      considered as significant. RESULTS: Monoka stents were performed for 45 eyes. A
      total of 75 questionnaire responses were analyzed. At the last follow-up of 24
      weeks, the anatomical and functional success rates were 93.3% (42/45). The
      changes in the mean total score (7.68 preoperatively to 0.82 at 24-week follow
      up) were statistically significant (P <= 0.001). The mean social impact scores
      showed significant improvement postoperatively from 4.06 to 0.53 (P <= 0.001).
      The mean lacrimal symptom score changed from a preoperative value of 3.62 to 0.28
      (P <= 0.001) at the last follow-up. Postoperative scoring correlated well with
      the anatomical and functional success rates. The symptom scores corroborated with
      changes in the clinical outcomes. CONCLUSION: Mini-Monoka stent dilatation is a
      very effective intervention for the management of primary punctal stenosis, and
      Lac-Q questionnaire is a simple and useful tool to evaluate the quality of
      outcomes in such cases.

PMID- 29380771
TI  - Ocular manifestations of isolated corneal bee sting injury, management
      strategies, and clinical outcomes.
AB  - PURPOSE: The purpose of this study is to describe the presenting features,
      management strategies, and clinical outcome following bee sting injury to the
      cornea. METHODS: Retrospective case series involving 11 eyes of 11 patients with
      corneal bee sting injuries who presented over a period of 2 years. Nine of these
      11 eyes had the presence of intact bee stinger in the cornea, which was removed
      immediately under an operating microscope and sent for microbiological and
      histopathological evaluation. The patients were managed as per the individual
      treatment protocol of the respective treating physicians. RESULTS: Six eyes
      (54.5%) had a good clinical outcome (best-corrected visual acuity [BCVA] >20/40)
      with medical therapy alone with no need for surgical intervention. Five eyes
      (45.5%) had a poor clinical outcome (BCVA <20/40) with medical therapy and
      required surgery; of which three required a combined penetrating keratoplasty
      with cataract surgery, while one required isolated cataract surgery and one
      underwent penetrating keratoplasty. Glaucoma was present in 3/5 eyes undergoing
      surgery, one of which required a trabeculectomy. Five of the six eyes who had a
      good clinical outcome with medical therapy alone had been treated with
      concomitant oral steroids, along with topical antibiotic-steroid combination
      therapy. CONCLUSION: Oral corticosteroid supplementation to the topical steroid
      antibiotic treatment in patients with corneal bee sting injury where corneal
      involvement and anterior reaction is severe at presentation or inflammation not
      ameliorating with topical steroids alone prevents serious vision-threatening
      complications such as corneal decompensation, cataract, and glaucoma.

PMID- 29380773
TI  - The Mini-Monoka punctocanaliculoplasty.

PMID- 29380775
TI  - Correction of upper eyelid entropion: Modified techniques are most welcome.

PMID- 29380774
TI  - Upper eyelid levator-recession and anterior lamella repositioning through the
      grey-line: Avoiding a skin-crease incision.
AB  - PURPOSE: This study aims to report a case series of upper eyelid cicatricial
      margin entropion with retraction, corrected through a grey-line approach only. We
      remind readers of the grey-line approach to levator recession (LR) and lamellar
      repositioning surgery. METHODS: A retrospective review of clinic notes and
      photographs of patients who underwent grey-line split (GLS), LR, release of
      orbital septum, recession of levator, advancement of posterior lamella and
      anterior lamellar repositioning without a skin crease incision, from December
      2015 to December 2016. Indications for surgery included mild-to-moderate
      cicatricial margin upper eyelid entropion, tarsal curling, and meibomian gland
      inversion. Patients requiring spacer interposition to lengthen the posterior
      lamella were excluded from the study. Parameters of the study included lid margin
      position, lid height, ocular surface health and symptom improvement. RESULTS:
      Eleven eyelids of eight patients were included in the study, and underwent the
      procedure described. Lid margin position measured as the marginal reflex distance
      lowered (improved) in 72.7% of patients. Lid margin eversion was achieved in all
      eyes (100%). Corneal punctate epithelial erosions markedly improved, being
      present in 72.7% of patients preoperatively, and only 9.1% of patients
      postoperatively. Eight of eleven eyes showed symptomatic improvement, with six
      (54.5%) being completely asymptomatic and two achieving partial relief. An added
      observation was a pretarsal show asymmetry in some patients which improved in
      36.4% of surgeries postoperatively. CONCLUSION: Upper eyelid LR with GLS and
      anterior lamella repositioning can all be performed through the plane of the
      split, avoiding a skin incision. Normal lid margin apposition was achieved in all
      eyes with 91% demonstrating a clear cornea and 72% having symptomatic
      improvement.

PMID- 29380776
TI  - A pilot study regarding basic knowledge of "cortical visual impairment in
      children" among ophthalmologists.
AB  - PURPOSE: A pilot study was done to evaluate knowledge regarding "cortical visual
      impairment (CVI) in children" among ophthalmologists. METHODS: This study was
      conducted during the annual conference of a zonal ophthalmological society. All
      ophthalmologists who attended the conference were requested to participate in
      this study. Those who agreed were given a validated questionnaire to assess
      knowledge regarding CVI. Cronbach's alpha of the questionnaire was 0.6.
      Participants were asked to respond to multiple choice questions by choosing the
      single best option. The responses obtained were then evaluated. RESULTS: The
      total number of registered delegates in the conference was 448. A total of 103
      ophthalmologists showed interest to participate in the study with a response rate
      of 22.9%. Only 89/103 interested delegates were included in the study as
      remaining were unaware of CVI. No participant gave correct answers to all
      questions. Although more than 80% of them knew the most common association (87%)
      and site of pathology (84%), only 52% were sure about clinical features and even
      lesser respondents (39%) knew that magnetic resonance imaging is the correct
      investigation of choice. The majority responded correctly that these children
      need eye examination (89%) and can be managed by rehabilitation through
      multidisciplinary approach (82%), but only 58% could recognize differential
      diagnoses and had a correct idea regarding the prognosis of CVI. There was no
      correlation between the number of patients diagnosed per month by the respondent
      with knowledge of the disease. CONCLUSION: In this pilot study, ophthalmologists
      were found to have limited knowledge regarding clinical features, investigation,
      differential diagnosis, and visual prognosis of CVI in children. There is a need
      to improve awareness regarding CVI among ophthalmologists.

PMID- 29380777
TI  - Are children with low vision adapted to the visual environment in classrooms of
      mainstream schools?
AB  - PURPOSE: The study aimed to evaluate the classroom environment of children with
      low vision and provide recommendations to reduce visual stress, with focus on
      mainstream schooling. METHODS: The medical records of 110 children (5-17 years)
      seen in low vision clinic during 1 year period (2015) at a tertiary care center
      in south India were extracted. The visual function levels of children were
      compared to the details of their classroom environment. The study evaluated and
      recommended the chalkboard visual task size and viewing distance required for
      children with mild, moderate, and severe visual impairment (VI). RESULTS: The
      major causes of low vision based on the site of abnormality and etiology were
      retinal (80%) and hereditary (67%) conditions, respectively, in children with
      mild (n = 18), moderate (n = 72), and severe (n = 20) VI. Many of the children
      (72%) had difficulty in viewing chalkboard and common strategies used for better
      visibility included copying from friends (47%) and going closer to chalkboard
      (42%). To view the chalkboard with reduced visual stress, a child with mild VI
      can be seated at a maximum distance of 4.3 m from the chalkboard, with the
      minimum size of visual task (height of lowercase letter writing on chalkboard)
      recommended to be 3 cm. For 3/60-6/60 range, the maximum viewing distance with
      the visual task size of 4 cm is recommended to be 85 cm to 1.7 m. CONCLUSION:
      Simple modifications of the visual task size and seating arrangements can aid
      children with low vision with better visibility of chalkboard and reduced visual
      stress to manage in mainstream schools.

PMID- 29380778
TI  - Expert comments on: Are children with low vision adapted to the visual
      environment in classrooms of mainstream schools?

PMID- 29380779
TI  - Pebble beach artifact: An apparent multicolor imaging maculopathy due to corneal
      desiccation.

PMID- 29380780
TI  - Inverted macular hole edges following an inverted internal limiting membrane
      transplantation surgery for large macular hole.

PMID- 29380781
TI  - Tuberous sclerosis complex with Best's vitelliform macular dystrophy: A combined
      presentation.

PMID- 29380782
TI  - Documentation of active bleed from retinal neovascularization during fluorescein
      angiography.

PMID- 29380783
TI  - Serendipitous use of light source of operating microscope in endoscopic
      dacryocystorhinostomy.

PMID- 29380784
TI  - "Comet-tail" lesions of pseudoxanthoma elasticum.

PMID- 29380785
TI  - Management challenge: Optic disc granuloma in pulmonary tuberculosis.

PMID- 29380786
TI  - Melanorrhea: Noncontiguous spread of palpebral conjunctival melanoma to the
      nasolacrimal duct.
AB  - A 42-year-old Asian Indian male with a history of conjunctival melanoma in the
      left eye presented with a recurrent tumor in the upper tarsal conjunctiva. The
      tumor was completely excised under margin control, followed by two-staged eyelid
      reconstruction. During the second stage of the eyelid reconstruction, a brown
      colored discharge was noted at the punctum, which on cytology was confirmatory of
      melanoma. Left dacryocystectomy with en bloc nasolacrimal duct (NLD) excision was
      performed. Histopathology demonstrated infiltration of the NLD by the tumor with
      no presence of melanoma in the lacrimal sac. Lacrimal oncorrhea is a term used to
      describe tumor spread by free-floating cells in the tear film. All conjunctival
      tumors carry a risk of tumor spread by oncorrhea.

PMID- 29380787
TI  - Primary squamous cell carcinoma arising from palpebral conjunctiva: A rare
      presentation.
AB  - Squamous cell carcinoma (SCC) of the conjunctiva usually arises from the limbal
      conjunctiva. Rarely, it can arise from the palpebral conjunctiva. We report a
      case of primary conjunctival SCC of the palpebral conjunctiva which was treated
      successfully.

PMID- 29380788
TI  - Reactivation of herpes simplex viral keratitis following the botulinum toxin
      injection.
AB  - We describe a case of 55-year-old male farmer presented with recurrent corneal
      abrasions with a spastic entropion in the left eye. Superior cornea showed
      typical nummular opacities suggestive resolved herpetic eye diseases. On further
      enquiry, he had similar episodes in the past. Contralateral eye was essentially
      normal. Following the botulinum toxin injection for the management of spastic
      entropion, subject developed reactivation of herpetic necrotizing stromal
      keratitis. Diagnostic corneal scrapings were negative for herpes simplex virus-1
      antigen by immunofluorescence assay and for DNA by molecular techniques. The case
      was successfully managed with topical steroids and antiviral medications.

PMID- 29380789
TI  - An unusual hydrops in keratoconus.
AB  - A young 19-year-old male was referred for the management of acute hydrops in the
      left eye. During follow-up, other eye cornea developed edematous bands as if
      hydrops was developing at two parallel sites. Edema progressed very slowly and
      new edema bands continued to develop. This creeping type of hydrops took 4 months
      to develop into typical hydrops. To the best of our knowledge, hydrops has always
      been reported to develop in an acute manner and at a single site. Our case is
      unusual because hydrops progressed very slowly and developed at multiple sites in
      a creeping manner.

PMID- 29380790
TI  - Unusual ulcerative keratitis caused by Prototheca wickerhamii in a diabetic
      patient.
AB  - The purpose of the study was to report a case of ulcerative keratitis caused by
      an unusual algae Prototheca wickerhamii in a diabetic patient. This study design
      was a case report. A 46-year-old male, who was a known diabetic for 3 years, had
      an injury to the left cornea with the sparks of fire from wielding at work that
      developed into an ulcerative keratitis over a period of next 3 months as the
      patient was not on any medication. Corneal scraping culture report and Vitek 2
      system investigation result confirmed it to be a P. wickerhamii infection. The
      patient was started on intensive topical 1% voriconazole and 5% natamycin for 1
      month and with no improvement subsequently underwent penetrating keratoplasty. No
      recurrence of infection postoperatively was noted. This opportunistic algae
      rarely known to cause human eye infections is so far reported in either patients
      with severe systemic immunosuppression causing posterior segment eye involvement
      or as postcorneal surgery infections. We report an ulcerative keratitis by P.
      wickerhamii in a diabetic patient post corneal trauma with no prior ocular
      surgery.

PMID- 29380791
TI  - High-resolution optical coherence tomography in a case of descemetocele managed
      with amniotic membrane transplantation.
AB  - Amniotic membrane transplantation is a useful in the management of corneal melts
      and descemetocele. We describe high-resolution anterior segment optical coherence
      tomography (OCT) (Optovue) in a patient with descemetocele who was managed
      surgically with amniotic membrane transplantation. A 60-year-old female presented
      with a corneal melt in the right eye. She was a case of rheumatoid arthritis and
      was on systemic treatment with immunomodulators. Slit lamp examination revealed a
      severe thinning paracentrally. High-resolution OCT was performed at the site of
      descemetocele. She underwent amniotic membrane transplantation using fibrin glue
      and bandage contact lens application. At 6 weeks postoperative, the bandage
      contact lens was removed. The area of thinning healed with scarring. OCT at the
      healed site revealed stable surface and an increase in stromal thickness to 281
      MU this case describes the utility of amniotic membrane in the healing of sterile
      corneal melts by providing tectonic support and its integration in the stroma.
      The stromal healing and increased thickness at the site of descemetocele could be
      delineated on high-resolution OCT imaging.

PMID- 29380792
TI  - Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.
AB  - We describe a case of spontaneous hyphema associated with anterior uveitis
      presents in a 69-year old female as the prominent sign of the intraocular spread
      of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes
      and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic
      lymphoma, characteristic findings on B-scan ultrasonography and magnetic
      resonance imaging scan, and identification of atypical lymphoid cells in aqueous
      sample established the diagnosis of intraocular metastasis of systemic DLBCL.
      Therefore, this report highlights that life-threatening malignant systemic
      lymphoma may masquerade as anterior segment ocular inflammation or neovascular
      glaucoma.

PMID- 29380793
TI  - Quantitative polymerase chain reaction analysis of serpiginous choroiditis with
      biopsy-proven testicular tuberculosis.
AB  - We report a case of a 47-year-old male patient presenting with diminution of
      vision in the left eye. The left eye fundus showed yellowish lesions with
      indistinct geographical margin extending over the posterior pole just abutting
      the macula, suggestive of diffuse choroiditis. The patient gave a history of
      testicular swelling for the past 2 years. Aqueous tap for polymerase chain
      reaction analysis was positive for IS6110 mycobacterial tuberculosis (TB) genome,
      and a biopsy of testicular sac was suggestive of tubercular epididymitis. A
      diagnosis of TB-multifocal serpiginoid choroiditis was established and was
      managed with anti-tubercular therapy and systemic steroids.

PMID- 29380794
TI  - Real-time polymerase chain reaction in acute retinal necrosis following
      encephalitis.
AB  - Acute retinal necrosis (ARN) following herpes simplex encephalitis (HSE) in an
      immunocompetent patient is a rare condition. Quantitative real-time polymerase
      chain reaction (qPCR) has made it possible to identify and quantify viral genome.
      We report a case of ARN following HSE managed with the help of qPCR. A 45-year
      old man developed ARN following HSE and was treated with intravenous acyclovir
      and intravitreal foscarnet. The retinitis did not respond initially and the qPCR
      demonstrated a rise in the number of copies of the HSV-1 viral genome. With
      continued treatment with intravenous acyclovir and intravitreal ganciclovir, the
      retinitis healed and the qPCR confirmed a reduction in the viral load. qPCR has a
      high sensitivity and specificity for HSV and is a useful tool for diagnosis and
      treatment of viral retinitis.

PMID- 29380795
TI  - Multimodal imaging characteristics of hydroxychloroquine retinopathy.
AB  - Hydroxychloroquine (HCQ) is known to cause retinal toxicity. Early detection of
      the toxicity is necessary to stop the drug in time. Multicolor imaging (MC) is a
      new noninvasive retinal imaging modality that simultaneously acquires three
      reflectance images of the retina using three individual lasers producing a
      composite image, thereby allowing analysis of changes at various levels within
      the retina. It is a new and promising addition to the retinal imaging armory. MC
      characteristics of HCQ toxicity are hitherto unreported. A 61-year-old female
      presented with history of HCQ intake (400 mg/day) for the last 6 years. She had
      retinopathy in both eyes. Multicolor composite image showed circumscribed
      perifoveal arcuate area of darkening, and infrared reflectance showed speckled
      hyperreflecetance in both eyes. MC imaging shows definite changes in HCQ
      toxicity, and it might emerge as a possible screening tool in future.

PMID- 29380796
TI  - Torpedo maculopathy: A primary choroidal capillary abnormality?
AB  - A 26-year-old healthy male patient's fundus revealed findings consistent with
      torpedo maculopathy. Swept-source optical coherence tomography (OCT) showed a
      dome-shaped elevation of the retina at the level of ellipsoid zone. On OCT
      angiography segmented at the level of the choriocapillaris, a cluster of
      convoluted fine vessels was seen, and further, deeper scans of the larger
      choroidal vessels showed a slower flow. From these observations along with the
      embryological correlation of choriocapillaris development, a possibility of an
      abnormality preventing proper fenestration of the choriocapillaris along the
      horizontal raphe being responsible for this anomaly is suggested.

PMID- 29380797
TI  - Torpedo maculopathy with multifocal central serous chorioretinopathy: A rare case
      report.
AB  - We present a very rare case of torpedo maculopathy (TM) with multifocal central
      serous chorioretinopathy. A 26-year-old male presented with painless loss of
      vision in the right eye of 2 months duration. Clinical examination showed a
      torpedo-shaped lesion temporal to fovea and subretinal fluid in foveal center.
      Fluorescein angiography showed multifocal leaks. Optical coherence tomography
      showed an optically clear space/neurosensory detachment at the site of lesion.
      Patient underwent focal laser to the leaks. TM is a rare congenital disorder
      detected accidentally during routine fundus examination. It is usually unilateral
      and does not affect vision.

PMID- 29380798
TI  - Bilateral arterial occlusions masking retinitis in a HIV-positive male.
AB  - We report an interesting case of 36-year-old HIV-positive male with uveitis,
      cilioretinal artery occlusion in OD, and superotemporal branch retinal artery
      occlusion in OS. Hypercoagulability, cardiovascular, and rheumatologic workups
      were unremarkable. Aqueous taps were negative for toxoplasma, viruses, and MTb by
      multiplex polymerase chain reaction. Patches of retinitis were seen on clearing
      of retinal edema. Serology was positive for toxoplasma and rickettsia. Management
      included doxycycline, azithromycin, bactrim DS, and oral steroids. Vision
      improvement to 6/60 and 6/24 in OD and OS refer to the right eye and left eye,
      respectively, were noted at 4-month follow-up. Infections should be considered in
      arterial occlusions associated with inflammation in HIV-positive individuals.

PMID- 29380800
TI  - An overlap case of Parry-Romberg syndrome and en coup de sabre with striking
      ocular involvement and anti-double-stranded DNA positivity.
AB  - Parry-Romberg syndrome (PRS) may overlap localized scleroderma (morphea) lesions
      with linear depression (en coup de sabre [ECDS]). Overlap case with PRS and ECDS
      was presented. Enophthalmos, uveitis, ocular torticollis, keratic linear
      precipitates, and anti-double-stranded DNA positivity were identified.
      Subendothelial keratic precipitates detected by an in vivo laser scanning
      confocal microscopy were the first profiled in the literature. Patients must be
      evaluated and followed up carefully by their clinics to prevent misdiagnosis and
      unnecessary procedures such as surgery of ocular torticollis as muscular
      torticollis.

PMID- 29380799
TI  - Relative anterior microphthalmos in oculodentodigital dysplasia.
AB  - Here, we report a patient with oculodentodigital dysplasia (ODDD) caused by the
      c. 413G>A, p.Gly138Asp mutation in the gap junction protein alpha-1 gene. The
      patient suffered from characteristic dysmorphic features of ODDD.
      Ophthalmological investigation disclosed microcornea and a shallow anterior
      chamber, as expected. Surprisingly, the patient had a normal axial length and
      moderate myopia on both eyes. To the best of our knowledge, this is the first
      report on ODDD associated with relative anterior microphthalmos and myopia.

PMID- 29380801
TI  - Time for introspection.

PMID- 29380802
TI  - Increasing the reliability of health information on internet.

PMID- 29380803
TI  - Keratoplasty in congenital primary aphakia.

PMID- 29380804
TI  - Our experience with strabismus surgery under topical anesthesia performed at a
      tertiary eye care center.

PMID- 29380805
TI  - Comment on: Femtosecond laser-assisted cataract surgery versus 2.2-mm clear
      corneal phacoemulsification.

PMID- 29380806
TI  - Reply to comment on: Femtosecond laser-assisted cataract surgery versus 2.2 mm
      clear corneal phacoemulsification.

PMID- 29380807
TI  - Comment on: Fungal keratitis: The Aravind Experience.

PMID- 29380808
TI  - Reply to Comment on: Fungal keratitis: The Aravind Experience.

PMID- 29380809
TI  - Comment on: Systemic analysis of ocular trauma by a new proposed ocular trauma
      classification.

PMID- 29380810
TI  - Comment on: Aflibercept for recurrent or recalcitrant polypoidal choroidal
      vasculopathy in Indian eyes: Early experience.

PMID- 29380811
TI  - Reply to comment on: Systematic analysis of ocular trauma by a new proposed
      ocular trauma classification.

PMID- 29380812
TI  - Reply to comment on: Aflibercept for recurrent or recalcitrant polypoidal
      choroidal vasculopathy in Indian eyes: Early experience.

PMID- 29380813
TI  - Comment on: Orbital dermatofibrosarcoma protuberans with frontal and ethmoid
      sinus involvement: A case report and brief review of literature.

PMID- 29380814
TI  - Reply to comment on: Orbital dermatofibrosarcoma protuberans with frontal and
      ethmoid sinus involvement: A case report and brief review of literature.

PMID- 29380815
TI  - Enhancement of Choriocapillaris Visualization in En Face Swept-Source Optical
      Coherence Tomography Angiography Images.
AB  - BACKGROUND Visualization of the choriocapillaris vessels using swept-source
      optical coherence tomography is a novel technique. However, en face images
      obtained with current commercial equipment using this method are still unclear.
      Therefore, using freely available image processing software, we have been able to
      enhance and clearly visualize single choriocapillaris blood vessels. MATERIAL AND
      METHODS We examined 4 swept-source optical coherence tomography en face images of
      the choriocapillaris in 2 male patients in both eyes and processed them using
      Image J software. RESULTS In our study, all images displayed clearly individual
      choriocapillaris vessels. CONCLUSIONS Implementation of this technique
      significantly improves visualization of the choriocapillaris. Further studies
      need to be carried out in order to validate this method of enhancement.

PMID- 29380816
TI  - Kidneys and women's health: key challenges and considerations.
AB  - The theme of World Kidney Day 2018 is 'kidneys and women's health: include,
      value, empower'. To mark this event, Nature Reviews Nephrology asked four leading
      researchers to discuss key considerations related to women's kidney health,
      including specific risk factors, as well as the main challenges and barriers to
      care for women with kidney disease and how these might be overcome. They also
      discuss policies and systems that could be implemented to improve the kidney
      health of women and their offspring and the areas of research that are needed to
      improve the outcomes of kidney disease in women.

PMID- 29380819
TI  - Variation in Pathologist Classification of Colorectal Adenomas and Serrated
      Polyps.
AB  - OBJECTIVES: Endoscopist quality measures such as adenoma detection rate (ADR) and
      serrated polyp detection rates (SPDRs) depend on pathologist classification of
      histology. Although variation in pathologic interpretation is recognized, we add
      to the literature by quantifying the impact of pathologic variability on
      endoscopist performance. METHODS: We used natural language processing to abstract
      relevant data from colonoscopy and related pathology reports performed over 2
      years at four clinical sites. We quantified each pathologist's likelihood of
      classifying polyp specimens as adenomas or serrated polyps. We estimated the
      impact on endoscopists' ADR and SPDR of sending their specimens to pathologists
      with higher or lower classification rates. RESULTS: We observed 85,526
      colonoscopies performed by 119 endoscopists; 50,453 had a polyp specimen, which
      were analyzed by 48 pathologists. There was greater variation across pathologists
      in classification of serrated polyps than in classification of adenomas. We
      estimate the endoscopist's average SPDR would be 0.5% if all their specimens were
      analyzed by the pathologist in our sample with the lowest classification rate and
      12.0% if all their specimens were analyzed by the pathologist with the highest
      classification rate. In contrast, the endoscopist's average ADR would be 28.5%
      and 42.4% if their specimens were analyzed by the pathologist with lowest and
      highest classification rate, respectively. CONCLUSIONS: There is significant
      variation in pathologic interpretation, which more substantially affects
      endoscopist SPDR than ADR.

PMID- 29380818
TI  - Renin cells in homeostasis, regeneration and immune defence mechanisms.
AB  - An accumulating body of evidence suggests that renin-expressing cells have
      developed throughout evolution as a mechanism to preserve blood pressure and
      fluid volume homeostasis as well as to counteract a number of homeostatic and
      immunological threats. In the developing embryo, renin precursor cells emerge in
      multiple tissues, where they differentiate into a variety of cell types. The
      function of those precursors and their progeny is beginning to be unravelled. In
      the developing kidney, renin-expressing cells control the morphogenesis and
      branching of the renal arterial tree. The cells do not seem to fully
      differentiate but instead retain a degree of developmental plasticity or
      molecular memory, which enables them to regenerate injured glomeruli or to alter
      their phenotype to control blood pressure and fluid-electrolyte homeostasis. In
      haematopoietic tissues, renin-expressing cells might regulate bone marrow
      differentiation and participate in a circulating leukocyte renin-angiotensin
      system, which acts as a defence mechanism against infections or tissue injury.
      Furthermore, renin-expressing cells have an intricate lineage and functional
      relationship with erythropoietin-producing cells and are therefore central to two
      endocrine systems - the renin-angiotensin and erythropoietin systems - that
      sustain life by controlling fluid volume and composition, perfusion pressure and
      oxygen delivery to tissues. However, loss of the homeostatic control of these
      systems following dysregulation of renin-expressing cells can be detrimental,
      with serious pathological events.

PMID- 29380820
TI  - Severity and Outcomes of Upper Gastrointestinal Bleeding With Bloody Vs. Coffee
      Grounds Hematemesis.
AB  - OBJECTIVES: Numerous reviews indicate bloody hematemesis signifies more severe
      bleeding than coffee-grounds hematemesis. We assessed severity and outcomes
      related to bleeding symptoms in a prospective study. METHODS: Consecutive
      patients presenting with hematemesis or melena were categorized as bloody emesis
      (N=1209), coffee-grounds emesis without bloody emesis (N=701), or melena without
      hematemesis (N=1069). We assessed bleeding severity (pulse, blood pressure) and
      predictors of outcome (hemoglobin, risk stratification scores) at presentation,
      and outcomes of bleeding episodes. The primary outcome was a composite of
      transfusion, intervention, or mortality. RESULTS: Bloody and coffee-grounds
      emesis were similar in pulse >=100 beats/min (35 vs. 37%), systolic blood
      pressure <=100 mm Hg (12 vs. 12%), and hemoglobin <=100 g/l (25 vs. 27%). Risk
      stratification scores were lower with bloody emesis. The composite end point was
      34.7 vs. 38.2% for bloody vs. coffee-grounds emesis; mortality was 6.6 vs. 9.3%.
      Hemostatic intervention was more common (19.4 vs. 14.4%) with bloody emesis (due
      to a higher frequency of varices necessitating endoscopic therapy), as was
      rebleeding (7.8 vs. 4.5%). Outcomes were worse with hematemesis plus melena vs.
      isolated hematemesis for bloody (composite: 62.4 vs. 25.6%; hemostatic
      intervention: 36.5 vs. 13.8%) and coffee-grounds emesis (composite: 59.1 vs.
      27.1%; hemostatic intervention: 26.4 vs. 8.1%). CONCLUSIONS: Bloody emesis is not
      associated with more severe bleeding episodes at presentation or higher mortality
      than coffee-grounds emesis, but is associated with modestly higher rates of
      hemostatic intervention and rebleeding. Outcomes with hematemesis are worsened
      with concurrent melena. The presence of bloody emesis plus melena potentially
      could be considered in decisions regarding timing of endoscopy.

PMID- 29380817
TI  - Sex-specific differences in hypertension and associated cardiovascular disease.
AB  - Although intrinsic mechanisms that regulate arterial blood pressure (BP) are
      similar in men and women, marked variations exist at the molecular, cellular and
      tissue levels. These physiological disparities between the sexes likely
      contribute to differences in disease onset, susceptibility, prevalence and
      treatment responses. Key systems that are important in the development of
      hypertension and cardiovascular disease (CVD), including the sympathetic nervous
      system, the renin-angiotensin-aldosterone system and the immune system, are
      differentially activated in males and females. Biological age also contributes to
      sexual dimorphism, as premenopausal women experience a higher degree of
      cardioprotection than men of similar age. Furthermore, sex hormones such as
      oestrogen and testosterone as well as sex chromosome complement likely contribute
      to sex differences in BP and CVD. At the cellular level, differences in cell
      senescence pathways may contribute to increased longevity in women and may also
      limit organ damage caused by hypertension. In addition, many lifestyle and
      environmental factors - such as smoking, alcohol consumption and diet - may
      influence BP and CVD in a sex-specific manner. Evidence suggests that
      cardioprotection in women is lost under conditions of obesity and type 2 diabetes
      mellitus. Treatment strategies for hypertension and CVD that are tailored
      according to sex could lead to improved outcomes for affected patients.

PMID- 29380821
TI  - Randomized Double-Blind Placebo-Controlled Crossover Trial for the Diagnosis of
      Non-Celiac Gluten Sensitivity in Children.
AB  - OBJECTIVES: Non-celiac gluten sensitivity (NCGS) is characterized by intestinal
      and extra-intestinal symptoms that are related to the ingestion of gluten in
      subjects who are not affected by either celiac disease (CD) or wheat allergy
      (WA). In this multicenter study, we aim for the first time to evaluate the
      prevalence of NCGS in pediatric subjects with chronic functional gastrointestinal
      symptoms associated with gluten ingestion using a double-blind placebo-controlled
      (DBPC) gluten challenge with crossover. METHODS: Among 1,114 children with
      chronic gastrointestinal symptoms (negative CD and WA), those exhibiting a
      positive correlation between symptoms and gluten ingestion were eligible for a
      diagnostic challenge including the following phases: run-in, open gluten-free
      diet (GFD) and DBPC crossover gluten challenge. Patients were randomized to
      gluten (10 g/daily) and placebo (rice starch) for 2 weeks each, separated by a
      washout week. The gluten challenge was considered positive in the presence of a
      minimum 30% decrease of global visual analogue scale between gluten and placebo.
      RESULTS: Out of 1,114 children, 96.7% did not exhibit any correlation with gluten
      ingestion. Thirty-six children were eligible; after the run-in and open GFD, 28
      patients entered the gluten challenge. Eleven children (39.2%; 95% CI: 23.6
      53.6%) tested positive. CONCLUSIONS: This is the first demonstration of the
      existence of NCGS in children that reinforce the need for a DBPC for the
      diagnosis as the diagnosis is ruled out in >60% of cases. The registration
      identifier in ClinicalsTrials.gov is NCT02431585.

PMID- 29380822
TI  - Hospitalizations for Autoimmune Hepatitis Disproportionately Affect Black and
      Latino Americans.
AB  - OBJECTIVES: The healthcare burden of autoimmune hepatitis (AIH) in the United
      States has not been characterized. We previously showed that AIH
      disproportionately affects people of color in a single hospital system. The
      current study aimed to determine whether the same disparity occurs nationwide.
      METHODS: We analyzed hospitalizations with a primary discharge diagnosis
      corresponding to the ICD-9 code for AIH in the National Inpatient Sample between
      2008 and 2012. For each racial/ethnic group, we calculated the AIH
      hospitalization rate per 100,000 population and per 100,000 all-cause
      hospitalizations, then calculated a risk ratio compared to the reference rate
      among whites. We used multivariable logistic regression models to assess for
      racial disparities and to identify predictors of in-hospital mortality during AIH
      hospitalizations. RESULTS: The national rate of AIH hospitalization was 0.73
      hospitalizations per 100,000 population. Blacks and Latinos were hospitalized for
      AIH at a rate 69% (P<0.001) and 20% higher (P<0.001) than whites, respectively.
      After controlling for age, gender, payer, residence, zip code income, region, and
      cirrhosis, black race was a statistically significant predictor for mortality
      during AIH hospitalizations (odds ratio (OR) 2.81, 95% confidence interval (CI)
      1.43, 5.47). CONCLUSIONS: Hospitalizations for AIH disproportionately affect
      black and Latino Americans. Black race is independently associated with higher
      odds of death during hospitalizations for AIH. This racial disparity may be
      related to biological, genetic, environmental, socioeconomic, and healthcare
      access and quality factors.

PMID- 29380823
TI  - Efficacy and Tolerability of Guanylate Cyclase-C Agonists for Irritable Bowel
      Syndrome with Constipation and Chronic Idiopathic Constipation: A Systematic
      Review and Meta-Analysis.
AB  - OBJECTIVES: Linaclotide and plecanatide are guanylate cyclase-C (GCC) agonists
      for the treatment of chronic idiopathic constipation (CIC) and irritable bowel
      syndrome with constipation (IBS-C). Our objective is to evaluate the efficacy and
      tolerability of GCC agonists based on data from multiple randomized controlled
      trials (RCTs). METHODS: We searched PubMED, EMBASE, Cochrane databases,
      clinicaltrials.gov, major conference abstracts, Food and Drug Administration
      (FDA) websites, and United States Securities and Exchange Commission filings of
      drug sponsors to identify RCTs of CIC or IBS-C patients. We assessed efficacy
      based on FDA-approved composite responder endpoints, diarrhea as an adverse
      event, and study withdrawal owing to diarrhea for each therapy. Trial results
      were pooled using DerSimonian and Laird random effects model of meta-analysis and
      exact logistic regression when appropriate with 95% confidence intervals. Meta
      regression was performed to compare outcomes between therapies adjusting for
      placebo event rate. RESULTS: Eight linaclotide trials (five CIC; three IBS-C) and
      seven plecanatide trials (four CIC; three IBS-C) evaluating 10,369 patients met
      inclusion criteria. FDA publications documented that different definitions for
      diarrhea were used in linaclotide vs. plecanatide trials. Both drugs were
      efficacious in treating CIC (linaclotide 72 MUg (Odds ratio (OR)=3.11, 95% CI
      1.81-5.34); linaclotide 145 MUg (OR=3.25, 2.15-4.91); plecanatide 3 mg (OR=1.99,
      1.57-2.51)) and IBS-C (linaclotide 290 MUg (OR=2.43, 1.48-3.98); plecanatide 3 mg
      (OR=1.87, 1.47-2.38); plecanatide 6 mg (OR=1.92, 1.48-2.48)). Diarrhea occurred
      in excess of placebo in treating CIC (linaclotide 72 MUg (OR=3.07, 1.97-4.77);
      linaclotide 145 MUg (OR=3.70, 2.69-5.10); plecanatide 3 mg (OR=3.86, 1.83-8.12))
      and IBS-C (linaclotide 290 MUg (OR=8.02, 5.20-12.37); plecanatide 3 mg (OR=5.55,
      1.62-19.00); plecanatide 6 mg (OR=4.13, 1.57-10.83)). Based on meta-regression,
      there were no statistically significant differences between therapies in odds
      ratios for efficacy, diarrhea, or diarrhea-related study withdrawals.
      CONCLUSIONS: Both linaclotide and plecanatide demonstrate similar efficacy and
      tolerability in treating IBS-C and CIC. No differences in odds of diarrhea were
      seen between linaclotide and plecanatide.

PMID- 29380824
TI  - Problem-based learning in primary care at University of Ribeirao Preto (UNAERP)
      in Brazil.

PMID- 29380825
TI  - Characterization of the binding interactions between EvaGreen dye and dsDNA.
AB  - Understanding the dsDNA.EG binding interaction is important because the EvaGreen
      (EG) dye is increasingly used in real-time quantitative polymerase chain
      reaction, high resolution melting analysis, and routine quantification of DNA. In
      this work, a binding isotherm for the interactions of EG with duplex DNA (poly
      dA17.poly-dT17) has been determined from the absorption and fluorescence spectra
      of the EG and dsDNA.EG complex. The isotherm has a sigmoidal shape and can be
      modeled with the Hill equation, indicating positive cooperativity for the binding
      interaction. A Scatchard plot of the binding data yields a concave-down curve in
      agreement with the Hill analysis of the binding isotherm for a positive
      cooperative binding interaction. Analysis of the Scatchard plot with the modified
      McGhee and von Hippel model for a finite one-dimensional homogeneous lattice and
      nonspecific binding of ligands to duplex DNA yields the intrinsic binding
      constant, the number of lattice sites occluded by a bound ligand, and the
      cooperativity parameter of 3.6 * 105 M-1, 4.0, and 8.1, respectively. The
      occluded site size of 4 indicates that moieties of the EG intercalate into the
      adjacent base pairs of the duplex DNA with a gap of 1 intercalation site between
      EG binding sites, as expected for a bifunctional molecule. Interestingly, at high
      [EG]/[base pair], the intercalation is disrupted. A model is proposed based on
      the fluorescence spectrum where the formation of anti-parallel stacked chains of
      EGs bound externally to the duplex DNA occur at these high ratios.

PMID- 29380826
TI  - A highly stable MnII phosphonate as a highly efficient catalyst for CO2 fixation
      under ambient conditions.
AB  - With coordinatively unsaturated metal centers decorating the channel walls, a
      MnII phosphonate exhibits highly efficient and substrate size-selective catalysis
      in the context of CO2 chemical conversion into cyclic carbonates under 1 atm
      pressure and at room temperature, proving to be a promising heterogeneous
      catalyst in an eco-friendly and energy efficient way.

PMID- 29380827
TI  - A label-free fluorescence assay for hydrogen peroxide and glucose based on the
      bifunctional MIL-53(Fe) nanozyme.
AB  - A label-free nanozyme MIL-53(Fe) with the dual-function of catalyzing and
      emitting fluorescence was utilized for turn-on fluorescence detection of hydrogen
      peroxide and glucose. The proposed strategy provides a cost-effective, safe and
      sensitive method for the design and development of multiple enzyme cascade assays
      for various biomolecules.

PMID- 29380828
TI  - Photoassociation of ultracold NaLi.
AB  - We perform photoassociation spectroscopy in an ultracold 23Na-6Li mixture to
      study the c3Sigma+ excited triplet molecular potential. We observe 50 vibrational
      states and their substructure to an accuracy of 20 MHz, and provide line strength
      data from photoassociation loss measurements. An analysis of the vibrational line
      positions using near-dissociation expansions and a full potential fit is
      presented. This is the first observation of the c3Sigma+ potential, as well as
      photoassociation in the NaLi system.

PMID- 29380832
TI  - Modulating PtPt metal-metal interactions through conformationally switchable
      molecular tweezer/guest complexation.
AB  - Herein a new organoplatinum(ii)-based molecular tweezer has been designed and
      synthesized, which displays pH-responsive mechanical transformation from the "U"-
      to "W"-shaped conformation. Pt(ii)Pt(ii) metal-metal interactions have been
      successfully incorporated into the resulting molecular tweezer/guest recognition
      motifs and self-assembled polymers, which can be modulated in response to pH
      variation.

PMID- 29380840
TI  - Probing the excited state dynamics of Venus: origin of dual-emission in
      fluorescent proteins.
AB  - Fluorescent proteins exhibit interesting excited state photochemistry, leading to
      bright fluorescence emission that renders their versatile biological role and
      wide use as biomarkers. A molecular-level mechanism of the excited state dynamics
      is desirable to pinpoint the origin of the bright fluorescence of these proteins.
      Here we present studies on a yellow fluorescent protein variant, Venus, and
      investigate the photophysics behind the dual fluorescence emission upon UV
      excitation. Based on our studies, we propose that the unique nature of the
      potential energy surface is responsible for the observation of minor fluorescence
      in Venus which is not seen in wild type GFP.

PMID- 29380844
TI  - Editorial: Geriatrics in the 21st Century.

PMID- 29380846
TI  - Mini Nutritional Assessment Short-Form (MNA-SF) Predicts Institutionalisation in
      an Intermediate Post-Acute Care Setting.
AB  - OBJECTIVES: The aim of the study was to investigate whether nutritional status as
      measured by the Mini Nutritional Assessment Short-Form (MNA-SF) predicts level of
      care of the discharge destination after post-acute care in a nursing home.
      DESIGN: Cohort study. SETTING: Post-acute intermediate care nursing home, 19-bed
      unit with increased multidisciplinary staff. PARTICIPANTS: Patients >=70 years in
      post-acute care (N=900) following an acute admission to the hospital.
      MEASUREMENTS: The predictive value of nutritional status, as measured by the MNA
      SF, on discharge destination was analysed by means of a multinomial logistic
      regression model with the MNA-SF as the independent variable, discharge
      destination as the dependent variable and age and living situation as co
      variates. The participants were grouped into three categories according to their
      discharge destination: home, other institution or readmitted to the hospital.
      RESULTS: A higher score on the MNA-SF significantly predicted a reduced risk of
      discharge to institution (adjusted OR=0.90 (95% CI=0.84;0.97), p=0.003).
      CONCLUSION: Nutritional status, as measured by the MNA-SF, predicted discharge
      destination from an intermediate care nursing home following acute
      hospitalisation. The findings underscore the value of nutritional assessment as
      part of overall clinical assessment and care planning prior to discharge. The
      findings may also imply that interventions to improve nutritional status could
      increase patients' ability to return home, as opposed to further
      institutionalisation, after hospitalisation.

PMID- 29380845
TI  - Occurrence of Malnutrition and Associated Factors in Community-Dwelling Older
      Adults: Those with a Recent Diagnosis of Cancer Are at Higher Risk.
AB  - OBJECTIVES: In older adults, nutritional health is essential for good quality of
      life and living independently at home. Especially in cancer patients,
      malnutrition is common and known to complicate treatment. This study aims to
      evaluate the nutritional status and its associated factors in community-dwelling
      older adults with and without cancer. DESIGN: This is an observational study.
      SETTING: This study focuses on older community-dwelling people. PARTICIPANTS:
      This study included older people with and without cancer (>=70 years). Cancer
      patients included patients with a new diagnosis of breast, lung, prostate, or
      colorectal cancer. MEASUREMENTS: Data collection included measures of nutritional
      status, quality of life, depression, fatigue, distress and functional status. We
      used multivariate logistic regression analysis to assess the association between
      personal characteristics and malnutrition. RESULTS: Data were available for 657
      people; 383 people without cancer and 274 with a cancer diagnosis. Overall,
      malnutrition was detected in 245 (37.5%) people; in cancer patients this was
      66.1%. Multivariate analysis showed that having cancer (OR 14.4, 95% CI: 8.01 -
      23.3), being male (OR 2.38, 95% CI: 1.49 - 3.70), having depression (OR 13.5, 95%
      CI: 6.02-30.0), distress (OR 2.60, 95% CI: 1.55 - 4.37) and impaired instrumental
      activities of daily living (IADL) (OR 2.63, 95% CI: 1.63 - 4.24) were associated
      with a higher risk of malnutrition. CONCLUSION: The prevalence of malnutrition in
      community-dwelling older people is high, particularly in patients with cancer.
      Benchmarking and routine screening of older patients may be helpful strategies to
      increase awareness of (risk of) malnutrition among professionals.

PMID- 29380847
TI  - Development and Psychometric Testing of a Novel Food Service Satisfaction
      Questionnaire for Food Service Staff of Aged Care Homes.
AB  - BACKGROUND: Food service staff are integral to delivery of quality food in aged
      care homes yet measurement of their satisfaction is unable to be performed due to
      an absence of a valid and reliable questionnaire. The aim of this study was to
      develop and perform psychometric testing for a new Food Service Satisfaction
      Questionnaire developed in Australia specifically for use by food service staff
      working in residential aged care homes (Flinders FSSQFSAC). METHODS: A mixed
      methods design utilizing both a qualitative (in-depth interviews, focus groups)
      and a quantitative approach (cross sectional survey) was used. Content validity
      was determined from focus groups and interviews with food service staff currently
      working in aged care homes, related questionnaires from the literature and
      consultation with an expert panel. The questionnaire was tested for construct
      validity and internal consistency using data from food service staff currently
      working in aged care homes that responded to an electronic invitation circulated
      to Australian aged care homes using a national database of email addresses.
      Construct validity was tested via principle components analysis and internal
      consistency through Cronbach's alpha. Temporal stability of the questionnaire was
      determined from food service staff undertaking the Flinders FSSQFSAC on two
      occasions, two weeks apart, and analysed using Pearson's correlations. RESULTS:
      Content validity for the Flinders FSSQFSAC was established from a panel of
      experts and stakeholders. Principle components analysis revealed food service
      staff satisfaction was represented by 61-items divided into eight domains: job
      satisfaction (alpha=0.832), food quality (alpha=0.871), staff training
      (alpha=0.922), consultation (alpha=0.840), eating environment (alpha=0.777),
      reliability (alpha=0.695), family expectations (alpha=0.781) and resident
      relationships (alpha=0.429), establishing construct validity in all domains, and
      internal consistency in all (alpha>0.5) except for "resident relationships"
      (alpha=0.429). Test-retest reliability coefficients ranged from 0.276 to 0.826
      dependent on domain, with test-retest reliability established in seven domains at
      r>0.4; an exception was "reliability" at r=0.276. CONCLUSIONS: The newly
      developed Flinders FSSQFSAC has acceptable validity and reliability and thereby
      the potential to measure satisfaction of food service staff working in
      residential aged care homes, identify areas for strategic change, measure
      improvements and in turn, improve the satisfaction and quality of life of both
      food service staff and residents of aged care homes.

PMID- 29380848
TI  - Tea Consumption Is Associated with Increased Bone Strength in Middle-Aged and
      Elderly Chinese Women.
AB  - OBJECTIVES: Previous studies found that tea consumption was related to a
      reduction in the risks of some chronic diseases, but limited data are available
      on bone health. This study aimed to examine the associations of tea consumption
      with hip bone strength in Chinese women. DESIGN: Cross-sectional study. SETTING:
      The participants were from the ongoing Guangzhou Nutrition and Health Study. This
      was a cohort study started in 2008. The examination data conducted between June
      2010 and December 2013 were used. PARTICIPANTS: A total of 1,495 Chinese women
      aged more than 40 years were included. MEASUREMENTS: Tea consumption, socio
      demographic information and lifestyle habits were collected by a face-to-face
      questionnaire. Hip bone mineral density (BMD) and geometric parameters, i.e.
      cross-sectional area (CSA), section modulus (Z) and buckling ratio (BR), were
      generated by dual-energy X-ray absorptiometry. The associations of tea
      consumption with bone phenotypes were detected by analysis of covariance and
      multiple linear regression models after adjusting for age, body mass index, years
      since menopause, physical activity, dietary-protein intake, dietary-calcium
      intake, calcium tablet intake, drinking status and smoking status. RESULTS: Tea
      drinkers (n = 732) had approximately 1.9% higher BMD (p < 0.05) and 3.6% lower BR
      (p < 0.05) than non-tea drinkers (n = 763). The dose-response relationships of
      BMD, BR or CSA with total tea consumption were identified (p-trend < 0.05). Tea
      drinking was found to be a significant and independent predictor of BMD (beta =
      0.068, p < 0.05) or BR (beta = -0.079, p < 0.05). CONCLUSION: Tea consumption was
      associated with increased bone strength in middle-aged and elderly Chinese women.

PMID- 29380849
TI  - Association of Long-Term Adherence to the MIND Diet with Cognitive Function and
      Cognitive Decline in American Women.
AB  - OBJECTIVES: There is increasing attention for dietary patterns as a potential
      strategy to prevent cognitive decline. We examined the association between
      adherence to a recently developed Mediterranean-DASH Intervention for
      Neurodegenerative Delay (MIND) diet with cognitive function and cognitive
      decline, taking into account the interaction between the apolipoprotein E
      epsilon4 genotype and the MIND diet. DESIGN: Population-based prospective cohort
      study. PARTICIPANTS: A total of 16,058 older women aged 70 and over from the
      Nurses' Health Study. MEASUREMENTS: Dietary intake was assessed five times
      between 1984 and 1998 with a 116-item Food Frequency Questionnaire. The MIND
      score includes ten brain-healthy foods and five unhealthy foods. Cognition was
      assessed four times by telephone from 1995 to 2001 (baseline) with the Telephone
      Interview for Cognitive Status (TICS) and by calculating composite scores of
      verbal memory and global cognition. Linear regression modelling and linear mixed
      modelling were used to examine the associations of adherence to the MIND diet
      with average cognitive function and cognitive change over six years,
      respectively. RESULTS: Greater long-term adherence to the MIND diet was
      associated with a better verbal memory score (multivariable-adjusted mean
      differences between extreme MIND quintiles=0.04 (95%CI 0.01-0.07), p
      trend=0.006), but not with cognitive decline over 6 years in global cognition,
      verbal memory or TICS. CONCLUSION: Long-term adherence to the MIND diet was
      moderately associated with better verbal memory in later life. Future studies
      should address this association within populations at greater risk of cognitive
      decline.

PMID- 29380850
TI  - A Comparison of Food Portion Size Estimation by Older Adults, Young Adults and
      Nutritionists.
AB  - OBJECTIVES: To investigate the ability of older adults, younger adults and
      nutritionists to assess portion size using traditional methods versus a computer
      based method. This was to inform the development of a novel dietary assessment
      method for older adults "The NANA system". DESIGN: Older and younger adults
      assessed the portion size of self-served portions of foods from a buffet style
      set up using traditional and computerised portion size assessment aids.
      Nutritionists assessed the portion size of foods from digital photographs using
      computerised portion size aids. These estimates were compared to known weights of
      foods using univariate analyses of covariance (ANCOVA). SETTING: The University
      of Sheffield, United Kingdom. SUBJECTS: Forty older adults (aged 65 years and
      over), 41 younger adults (aged between 18 and 40 years) and 25 nutritionists.
      RESULTS: There was little difference in the abilities of older and younger adults
      to assess portion size using both assessment aids with the exception of small
      pieces morphology. Even though the methods were not directly comparable among the
      test groups, there was less variability in portion size estimates made by the
      nutritionists. CONCLUSION: Older adults and younger adults are similar in their
      ability to assess food portion size and demonstrate wide variability of
      estimation compared to the ability of nutritionists to estimate portion size from
      photographs. The results suggest that the use of photographs of meals consumed
      for portion size assessment by a nutritionist may improve the accuracy of dietary
      assessment. Improved portion size assessment aids are required for all age
      groups.

PMID- 29380851
TI  - Effects of Milk Proteins Supplementation in Older Adults Undergoing Resistance
      Training: A Meta-Analysis of Randomized Control Trials.
AB  - BACKGROUND: Older adults experience age-related physiological changes that affect
      body weight and body composition. In general, nutrition and exercise have been
      identified as potent stimulators of protein synthesis in skeletal muscle. Milk
      proteins are excellent sources of all the essential amino acids and may represent
      an ideal protein source to promote muscle anabolism in older adults undergoing
      resistance training. However, several randomized control trials (RCTs) have
      yielded mixed results on the effects of milk proteins supplementation in
      combination with resistance training on body weight and composition. METHODS:
      PubMed, Web of Science and Cochrane databases were searched for literature that
      evaluated the effects of milk proteins supplementation on body weight and
      composition among older adults (age >= 60 years) undergoing resistance training
      up to September 2016. A random-effects model was used to calculate the pooled
      estimates and 95% confidence intervals (CIs) of effect sizes. RESULTS: The final
      analysis included 10 RCTs involving 574 participants (mean age range from 60 to
      80.8 years). Overall, the combination of milk proteins supplementation and
      resistance training did not have significant effect on fat mass (0.30, 95% CI 
      0.25, 0.86 kg) or body weight (1.02, 95% CI: -0.01, 2.04 kg). However, a positive
      effect of milk proteins supplementation paired with resistance training on fat
      free mass was observed (0.74, 95% CI 0.30, 1.17 kg). Greater fat-free mass gains
      were observed in studies that included more than 55 participants (0.73, 95% CI
      0.30, 1.16 kg), and in studies that enrolled participants with aging-related
      medical conditions (1.60, 95% CI 0.92, 2.28 kg). There was no statistical
      evidence of publication bias among the studies. CONCLUSION: Our findings provide
      evidence that supplementation of milk protein, in combination with resistance
      training, is effective to elicit fat-free mass gain in older adults.

PMID- 29380852
TI  - Physical Activity Types and Health-Related Quality of Life among Middle-Aged and
      Elderly Adults: The Rotterdam Study.
AB  - OBJECTIVES: Physical activity (PA) is associated with health-related quality of
      life (HRQL). The specific PA types that provide beneficial effects in an older
      population remain unclear. We assessed the association of total PA, walking,
      cycling, domestic work, sports and gardening with HRQL in middle-aged and elderly
      adults. DESIGN: Cross-sectional study. SETTING: Rotterdam, the Netherlands.
      PARTICIPANTS: 5,554 participants, with a mean age of 69 years. MEASUREMENTS:
      Total PA was categorized in five groups to evaluate the dose-response effect of
      PA and specific PA types were categorized in tertiles. HRQL was measured with the
      EuroQoL 5-dimension. The outcome of every HRQL domain (i.e. mobility, self-care,
      daily activities, pain and mood) was expressed as having any problems versus not
      having problems. Logistic and linear regression analyses were used, adjusting for
      confounders, to examine associations of total PA and PA types with HRQL domains.
      RESULTS: In both middle-aged (<65 years) and elderly adults (>65 years), we found
      a dose-response association between total PA and better HRQL (i.e. lower odds of
      having problems in HRQL domains). In the middle-aged, sports was the only PA type
      associated with lower odds of having problems with all HRQL domains. In the
      elderly, all PA types were associated with less problems with HRQL domains, but
      cycling contributed most to the beneficial effect. CONCLUSIONS: Total PA was
      associated with better HRQL. Sports and cycling were the activity types that
      contributed most to this association in the middle-aged and elderly,
      respectively. Since PA levels tend to decline with aging, cycling and sports
      should be promoted with the aim to improve HRQL.

PMID- 29380853
TI  - Oral Health Indicators for Risk of Malnutrition in Elders.
AB  - OBJECTIVES: Using both clinical parameters and subjective measures of oral
      health, this study aimed to identify useful oral health indicators for the risk
      of malnutrition in elders. DESIGN: Cross-sectional study. SETTING: Five community
      centers run by non-government organizations (NGOs). PARTICIPANTS: 195 community
      dwelling elders (65 or above). MEASUREMENTS: An interviewer-administered
      questionnaire was completed to collect information on elders' socio-demographic
      background and oral health perception and practice. Their number of teeth, number
      of occluding tooth pairs, dental caries, and periodontal condition were examined.
      General Oral Health Assessment Index (GOHAI), an instrument for assessing oral
      health related quality of life (OHQoL), was used as a subjective measure of oral
      health. The elders' nutritional status was evaluated by using the Mini
      Nutritional Assessment (MNA). RESULTS: The mean (SD) DFT was 3.3 (3.1). Over 60%
      of elders had periodontal pockets; 33% had fewer than 20 teeth and 6% were
      edentulous. The mean (SD) of occluding tooth pairs was 7.1 (4.8). The mean (SD)
      total GOHAI score was 56.4 (8.0); 60% reported negative impact of oral health on
      their quality of life. The mean (SD) MNA score was 25.0 (2.9); 30% had
      malnutrition or were at risk. After controlling for socio-demographic factors,
      none of the clinical indicators (dental caries, periodontal status, number of
      teeth, and number of occluding tooth pairs) were associated with risk of
      malnutrition (all p>0.05). Poorer OHQoL indicated a higher chance for
      malnutrition in both adjusted models (OR of 0.914; 95% CI of 0.850-0.982; p=0.014
      and OR of 0.915; 95% CI of 0.852-0.984; p=0.017). Tooth loss and untreated
      decayed teeth (DT) were significant/marginally significant determinants of poor
      OHQoL. CONCLUSION: Elders' tooth loss and unmet treatment need for dental caries
      were associated with compromised quality of life, which indicated increased
      likelihood for malnutrition.

PMID- 29380854
TI  - Association between Body Mass Index and All-Cause Mortality among Oldest Old
      Chinese.
AB  - OBJECTIVES: To examine the association between BMI and all-cause mortality in the
      oldest old (>=80 years). DESIGN: The study used a prospective cohort study
      design. SETTING: Chinese Longitudinal Healthy Longevity Survey (CLHLS) between
      1998/99 and 2011. POPULATION: 8026 participants aged 80 years and older were
      followed every two to three years. MEASUREMENTS: Body weight and knee height were
      measured. Height was calculated based on knee height using a validated equation.
      Deaths were ascertained from family members during follow-up. RESULTS: The mean
      BMI was 19.8 (SD 4.5) kg/m2. The prevalence of underweight, overweight and obese
      was 37.5%, 10.2% and 4.4%, respectively. There were 5962 deaths during 29503
      person-years of follow-up. Compared with normal weight, underweight was
      associated with a higher mortality risk (HRs: 1.20 (95%CI 1.13-1.27) but
      overweight (HR 0.89 (95%CI 0.81-0.99)) were associated with a lower risk. Obesity
      had a HR 0.91 (95%CI 0.78-1.05) for mortality. CONCLUSION: Among oldest old
      Chinese, underweight is associated with an increased risk of all-cause mortality
      but overweight is associated with a reduced risk. Interventions to reduce
      undernutrition should be given priority among the oldest old Chinese.

PMID- 29380855
TI  - Single-Arm Resistance Training Study to Determine the Relationship between
      Training Outcomes and Muscle Growth Factor mRNAs in Older Adults Consuming
      Numerous Medications and Supplements.
AB  - OBJECTIVES: Determine if the muscle mRNA levels of three growth factors (insulin
      like growth factor-1 [IGF1], ciliary neurotropic factor [CNTF], and vascular
      endothelial growth factor-D [VEGFD]) are correlated with muscle size and strength
      gains from resistance exercise while piloting a training program in older adults
      taking medications and supplements for age-associated problems. DESIGN: Single
      arm prospective study. SETTING: US Veterans Affairs hospital. PARTICIPANTS: Older
      (70+/-6 yrs) male Veterans (N=14) of US military service. INTERVENTION: Thirty
      five sessions of high-intensity (80% one-rep max) resistance training including
      leg press, knee curl, and knee extension to target the thigh muscles.
      MEASUREMENTS: Vastus lateralis biopsies were collected and body composition
      (DEXA) was determined pre- and post-training. Simple Pearson correlations were
      used to compare training outcomes to growth factor mRNA levels and other
      independent variables such as medication and supplement use. RESULTS: Average
      strength increase for the group was >= 25% for each exercise. Subjects averaged
      taking numerous medications (N=5+/-3) and supplements (N=2+/-2). Of the growth
      factors, a significant correlation (R>0.7, P<=0.003) was only found between pre
      training VEGFD and gains in lean thigh mass and extension strength. Mass and
      strength gains were also correlated with use of alpha-1 antagonists (R=0.55,
      P=0.04) and pre-training lean mass (R=0.56, P=0.04), respectively. CONCLUSIONS:
      Muscle VEGFD, muscle mass, and use of alpha-1 antagonists may be predisposing
      factors that influence the response to training in this population of older
      adults but additional investigation is required to determine if these
      relationships are due to muscle angiogenesis and blood supply.

PMID- 29380856
TI  - Peripheral Blood Leukocyte Telomere Length Is Associated with Age but Not Renal
      Function: A Cross-Sectional Follow-Up Study.
AB  - OBJECTIVES: We aimed to evaluate the relationship between baseline renal function
      and changes in telomere length in Han Chinese. METHODS: The telomere restriction
      fragment (TRF) length of leukocytes in the peripheral blood was measured in
      healthy volunteers recruited in 2014. The estimated glomerular filtration rate
      (eGFR) was calculated based on serum creatinine (Scr) and serum cystatin C (CysC)
      eGFRcys and eGFRScr-cys through the Cockcroft-Gault formula (eGFRC-G) or the
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI / eGFRCKD-EPI)
      equation. The correlation between telomere length changes over time and renal
      function was analyzed. RESULTS: Leukocyte TRF lengths were negatively correlated
      to age (r = -0.393, p < 0.001) and serum CysC (r = -0.180, p < 0.01), while
      positively associated with eGFRCKD-EPI, eGFRC-G, eGFRcys, and eGFRScr-cys (r =
      0.182, 0.122, 0.290, and 0.254 respectively, p < 0.01). The 3-year change of
      telomere length was 46 bp/years. When adjusted for age, the associations between
      telomere length changes and baseline, subsequent TRF lengths, and serum CysC were
      no longer present. No association was observed between TRF length changes and
      renal function. CONCLUSION: The rate of telomere length changes was affected by
      age and baseline telomere length. The telomere length changes might be important
      markers for aging.

PMID- 29380858
TI  - Dementia and Death After Stroke in Older Adults During a 10-year Follow-up:
      Results from a Competing Risk Model.
AB  - OBJECTIVES: To investigate the association between stroke and incident dementia
      in the presence of a competing risk of death. METHODS: This study used the
      National Health Insurance Service-Senior (NHIS-Senior) claim database from 2002
      to 2013 (n = 22,792). Stroke (I69.0-I69.9) and dementia (F01-F03, G30, G31.1)
      patients were defined by the International Classification of Disease 10th
      revision. The association of stroke with dementia or death was assessed with Cox
      proportional hazards model and competing-risk model. RESULTS: During the 10-year
      follow-up period, there were 1,307 dementia events (5.7%) and 9,272 deaths
      (40.7%). In the Cox model, the adjusted hazard ratio (HR) for dementia was 2.37
      times higher in those who experienced strokes, compared with the non-stroke group
      (95% CI: 2.23, 2.51). In the presence of death as competing event, stroke was
      associated with an elevated dementia incidence (HR = 2.06, 95% CI: 1.92, 2.20).
      CONCLUSION: Stroke was significantly associated with an increased risk of
      incident dementia, with the magnitude of the association being attenuated in the
      competing risk model.

PMID- 29380857
TI  - The Impact of Dietary Factors on Indices of Chronic Disease in Older People: A
      Systematic Review.
AB  - OBJECTIVES: There has been little evaluation of the evidence relating dietary
      factors to functional capacity in older adults. The aims were to i) conduct a
      systematic review of studies assessing dietary factors in relation to six key
      functional indicators which impact on quality of life in adults >=65 yrs: non
      fatal cardiovascular events, cognition, mental health, falls and fractures,
      physical health (muscle mass, strength) and frailty; and ii) assess if there was
      sufficient evidence to devise food-based dietary recommendations. DESIGN:
      Systematic review. PARTICIPANTS: Cross-sectional and prospective cohort studies
      were included together with intervention studies that evaluated food/drink
      interventions (excluding supplements). Evidence base statements were determined
      according to the GRADE (Grades of Recommendation, Assessment, Development and
      Evaluation) levels of evidence criteria (Grades (A-excellent; B-good; C
      satisfactory; D-poor). RESULTS: There was good evidence that the Mediterranean
      type diet (MD) reduced the risk of non-fatal cardiovascular events (Grade B) and
      reduced cognitive decline (Grade B). There was some evidence indicating that a MD
      decreases the likelihood of frailty (Grade C), consistent but weaker evidence
      that >=3 servings/d of vegetables is associated with reduced cognitive decline
      (Grade D), a modest increase in protein may be associated with improved cognition
      (Grade C) and decreased frailty (Grade C), and that protein plus resistance
      exercise training in frail elderly may enhance physical strength (Grade C).
      CONCLUSION: It is recommended that older adults adopt the characteristics of a
      Mediterranean type diet such as including olive oil and eating >=3 servings/d of
      vegetables to reduce their risk of chronic disease, impaired cognition and
      frailty. Consumption of dietary protein above the current dietary requirements
      would be recommended to reduce risk of frailty and impaired cognition. A modest
      increase in dietary protein when combined with resistance exercise would be
      recommended to help maintain muscle mass and strength and to enhance functional
      capacity.

PMID- 29380859
TI  - Comparative Study for the Association of Mitochondrial Haplogroup F+ and
      Metabolic Syndrome between Longevity and Control Population in Guangxi Zhuang
      Autonomous Region, China.
AB  - BACKGROUND: Our previous study suggested that mitochondrial haplogroup F (mtDNA
      F) was a longevity-associated biomarker, but the effect of mitochondrial
      haplogroup F on longevity individuals with metabolic syndrome (MetS) was not
      clear. Thus we explored the association between mtDNA F and MetS among longevity
      and control population in Guangxi Zhuang Autonomous Region, China. METHOD: A
      total of 793 individuals consisting of 307 long-lived participants and 486 local
      healthy controls were involved in this study. Genotypes of mtDNA F were amplified
      by polymerase chain reaction and Sanger sequenced. MetS was defined according to
      the revised National Cholesterol Education Program's Adult Treatment Panel III
      (NCEP ATPIII ) criteria. RESULTS: The prevalence of MetS in longevity group
      (28.0%) was higher than that (18.5%) in control group (P=0.002). Through the case
      control stratify analysis, the prevalence of MetS in mtDNA F+ longevity
      individuals (29.8%) was 4.6 fold higher than that (5.3%) in local control group
      (P<0.001). However, after further longevity-only analysis, no association between
      MetS and mtDNA F+ in longevity group was observed (P=0.167). Following same
      analysis of two variables in control group, we found that the prevalence of MetS
      in mtDNA F- (95.8%) was higher than that in mtDNA F+ (5.3%); conversely, the
      prevalence of non-metabolic syndrome (NMetS) in mtDNA F+ (94.7%) was markedly
      higher than that in mtDNA F- (4.2%) (P<0.001). CONCLUSION: We demonstrated that
      mtDNA F+ , as a molecuar biomarker, might not only confer beneficial effect to
      resistance against MetS but also function as a positive factor for long-life span
      among the population in Guangxi Zhuang Autonomous Region, China.

PMID- 29380860
TI  - Ultraviolet light and melanoma.
AB  - Melanoma is a clinically heterogeneous disease, and current strategies for
      treatment of the primary tumour are based on pathological criteria alone. In the
      recent past, several DNA-sequencing and RNA-sequencing studies of primary and
      advanced melanoma samples have identified unique relationships between somatic
      mutations, genomic aberrations, and the genetic fingerprint of ultraviolet
      radiation (UVR). The recurrent patterns of genomic alterations reveal different
      disease pathways, drug targets and mechanisms limiting drug response. Here, we
      examine the known associations between the molecular categories of melanoma and
      the multidimensional UVR damage. Copyright (c) 2018 Pathological Society of Great
      Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29380861
TI  - All-electron relativistic computations on the low-lying electronic states, bond
      length, and vibrational frequency of CeF diatomic molecule with spin-orbit
      coupling effects.
AB  - Ab initio all-electron computations have been carried out for Ce+ and CeF,
      including the electron correlation, scalar relativistic, and spin-orbit coupling
      effects in a quantitative manner. First, the n-electron valence state second
      order multireference perturbation theory (NEVPT2) and spin-orbit configuration
      interaction (SOCI) based on the state-averaged restricted active space
      multiconfigurational self-consistent field (SA-RASSCF) and state-averaged
      complete active space multiconfigurational self-consistent field (SA-CASSCF)
      wavefunctions have been applied to evaluations of the low-lying energy levels of
      Ce+ with [Xe]4f1 5d1 6s1 and [Xe]4f1 5d2 configurations, to test the accuracy of
      several all-electron relativistic basis sets. It is shown that the mixing of
      quartet and doublet states is essential to reproduce the excitation energies.
      Then, SA-RASSCF(CASSCF)/NEVPT2 + SOCI computations with the Sapporo(-DKH3)-2012
      QZP basis set were carried out to determine the energy levels of the low-lying
      electronic states of CeF. The calculated excitation energies, bond length, and
      vibrational frequency are shown to be in good agreement with the available
      experimental data. (c) 2018 Wiley Periodicals, Inc.

PMID- 29380862
TI  - Initial validation of the Burden of Disease in Atopic Eczema instrument, a
      quality-of-life measure for adult atopic dermatitis.

PMID- 29380863
TI  - Catechol 2,3-dioxygenase from a new phenolic compound degrader Thauera sp. K11:
      purification and biochemical characterization.
AB  - Catechol 2,3-dioxygenase (C23O) from a new phenolic compound degrader Thauera sp.
      K11 was purified and characterized. The native form of the enzyme was determined
      as a homotetramer with a molecular weight of 140 kDa, and its isoelectric point
      was close to 6.4. One iron per enzyme subunit was detected using atom absorption
      spectroscopy, and the effective size of C23O in its dilute solution (0.2 g L-1 ,
      pH 8.0) was 14.5 nm. The optimal pH and temperature were 8.4 and 45  degrees C,
      respectively. The addition of Mg2+ , Cu2+ , Fe2+ , and Mn2+ could improve the
      enzyme activity, while Ag+ was found to be a strong inhibitor. C23O was stable in
      alkali conditions (pH 7.6-11.0) and thermostable below 50  degrees C. The final
      purified C23O had a sheet content of 53%, consistent with the theoretical value.
      This showed that the purified catechol 2,3-dioxygenase folded with a reasonable
      secondary structure.

PMID- 29380864
TI  - The treatment outcomes and dose de-escalation of desloratadine up-dosing in
      chronic spontaneous urticaria.
AB  - BACKGROUND: An increase in dosages up to fourfold of second generation
      antihistamines is recommended for recalcitrant chronic spontaneous urticaria
      (CSU). No regimen guidelines about dose de-escalation, however, are mentioned
      once the disease is controlled. OBJECTIVE: To demonstrate the treatment outcomes
      and dose reduction in desloratadine assessed using the urticarial activity score
      over 7 consecutive days. METHODS: Medical records of all patients with CSU
      treated with desloratadine were collected retrospectively during a period from
      January 2010 to December 2013. RESULTS: Sixty-seven (94.4%) patients had
      remission of the disease with variable doses of desloratadine. The patients who
      had CSU concomitant with antithyroid antibodies or high erythrocyte sedimentation
      rates had a greater tendency not to respond to the standard dose. Once the
      disease was completely controlled, 67 patients finished the treatment, but 63
      (94%) patients had recurrent symptoms. Sixty-three patients took the same dose
      that induced the response for a further 4 weeks before stopping or reducing the
      dose, 41/63 (65.1%), however developed urticaria again. Forty-one patients took
      the same dose for a further 8 weeks; only 2/41 (4.9%) patients developed the rash
      again. The mean follow-up period after the disease was controlled was 7.5 months.
      CONCLUSION: Most patients need higher than the standard doses to obtain
      remission. Once the disease is completely controlled, however, maintenance of the
      same dosage for at least 8 weeks before dose reduction is suggested in order to
      avoid recurrence of the symptoms.

PMID- 29380865
TI  - Nasopharyngeal sialoceles in 11 brachycephalic dogs.
AB  - OBJECTIVE: To report clinical features, diagnosis, surgical treatment, and
      outcomes of brachycephalic dogs with nasopharyngeal sialoceles (NPS). STUDY
      DESIGN: Retrospective case series. ANIMALS: Eleven brachycephalic dogs with NPS.
      METHODS: Diagnosis of NPS was based on identification of cystic nasopharyngeal
      masses containing saliva-like mucoid material on retroflexed endoscopy. Biopsies
      were obtained to support the diagnosis. Surgical deroofing was performed under
      endoscopic guidance, and endoscopic examination was repeated at least 3 months
      after surgery. The owners rated the outcome of surgery via a follow-up telephone
      inquiry. RESULTS: Pugs (n = 8), French bulldogs (n = 2), and English bulldogs (n
      = 1) were included in this study. Eight of the NPS were ventral, 6 were
      obstructive, and 2 were multiple; both the obstructive and the multiple
      sialoceles were ventral. Surgical deroofing of the sialoceles was performed under
      endoscopic guidance with biopsy forceps in 5 cases and by diode laser in 6 cases.
      No recurrence was diagnosed. Ten of 11 owners reported that they were satisfied
      with the outcome. CONCLUSIONS AND CLINICAL SIGNIFICANCE: NPS may be an uncommon
      consequence of chronic nonphysiologic mechanical stress causing changes in minor
      nasopharyngeal salivary glands. Direct visualization by nasopharyngoscopy is the
      best technique for detection of NPS, and we advise routine examination of the
      nasopharynx by endoscope in all brachycephalic dogs before performing surgery.
      Either endoscopic guided biopsy forceps or diode laser surgery can be used for
      noninvasive, rapid, and effective resolution of NPS in all of the dogs.

PMID- 29380867
TI  - Asthma- and IgE-associated polymorphisms affect expression of TH 17 genes.

PMID- 29380866
TI  - Evaluation of a method to assess digitally recorded surgical skills of novice
      veterinary students.
AB  - OBJECTIVE: To evaluate a method to assess surgical skills of veterinary students
      that is based on digital recording of their performance during closure of a
      celiotomy in canine cadavers. SAMPLE POPULATION: Second year veterinary students
      without prior experience with live animal or simulated surgical procedure (n =
      19) METHODS: Each student completed a 3-layer closure of a celiotomy on a canine
      cadaver. Each procedure was digitally recorded with a single small wide-angle
      camera mounted to the overhead surgical light. The performance was scored by 2 of
      5 trained raters who were unaware of the identity of the students. Scores were
      based on an 8-item rubric that was created to evaluate surgical skills that are
      required to close a celiotomy. The reliability of scores was tested with
      Cronbach's alpha, intraclass correlation, and a generalizability study. RESULTS:
      The internal consistency of the grading rubric, as measured by alpha, was .76.
      Interrater reliability, as measured by intraclass correlation, was 0.64. The
      generalizability coefficient was 0.56. CONCLUSION: Reliability measures of 0.60
      and above have been suggested as adequate to assess low-stakes skills. The task
      specific grading rubric used in this study to evaluate veterinary surgical skills
      captured by a single wide-angle camera mounted to an overhead surgical light
      produced scores with acceptable internal consistency, substantial interrater
      reliability, and marginal generalizability. IMPACT: Evaluation of veterinary
      students' surgical skills by using digital recordings with a validated rubric
      improves flexibility when designing accurate assessments.

PMID- 29380868
TI  - On the ecological significance of pollen color: a case study in American trout
      lily (Erythronium americanum).
AB  - Evolutionary ecologists seek to explain the processes that maintain variation
      within populations. In plants, petal color variation can affect pollinator
      visitation, environmental tolerance, and herbivore deterrence. Variation in
      sexual organs may similarly affect plant performance. Within-population variation
      in pollen color, as occurs in the eastern North American spring ephemeral
      Erythronium americanum, provides an excellent opportunity to investigate the
      maintenance of variation in this trait. Although the red/yellow pollen-color
      polymorphism of E. americanum is widely recognized, it has been poorly
      documented. Our goals were thus (1) to determine the geographic distribution of
      the color morphs and (2) to test the effects of pollen color on components of
      pollen performance. Data provided by citizen scientists indicated that
      populations range from monomorphic red, to polymorphic, to monomorphic yellow,
      but there was no detectable geographic pattern in morph distribution, suggesting
      morph occurrence cannot be explained by a broad-scale ecological cline. In field
      experiments, we found no effect of pollen color on the probability of predation
      by the pollen-feeding beetle Asclera ruficollis, on the ability of pollen to
      tolerate UV-B radiation, or on siring success (as measured by the fruit set of
      hand-pollinated flowers). Pollinators, however, exhibited site-specific pollen
      color preferences, suggesting they may act as agents of selection on this trait,
      and, depending on the constancy of their preferences, could contribute to the
      maintenance of variation. Collectively, our results eliminate some hypothesized
      ecological effects of pollen color in E. americanum, and identify effects of
      pollen color on pollinator attraction as a promising direction for future
      investigation.

PMID- 29380869
TI  - Current controversies in prenatal diagnosis 3: Fetal MRI should be performed in
      all prenatally detected fetuses with a major structural abnormality.

PMID- 29380870
TI  - Detection and characterization of the ferric uptake regulator (fur) gene in
      Plesiomonas shigelloides.
AB  - : Iron availability plays an important role in the virulence of micro-organisms,
      which develops different systems for iron acquisition. The expression of genes
      involved in iron uptake systems is usually regulated by Fur, a transcriptional
      regulator. Plesiomonas shigelloides is a Gram-negative food- and water-borne
      enteropathogen. Even though the mechanisms involved in the pathogenicity of P.
      shigelloides are not properly elucidated, iron seems to be implicated in the
      development of human infections and in the production of potential virulence
      factors; however, detection and characterization of fur gene has not been
      performed in this bacterium. In this work the presence of a conserved fur gene
      was determined in six strains of P. shigelloides. The expression of fur was
      studied under different culture conditions and it was demonstrated to be higher
      when the micro-organism was cultured under iron-restricted than under iron
      abundance conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and
      Impact of the Study: This study provides evidence of the presence of a conserved
      fur gene in strains of Plesiomonas shigelloides. Expression of this gene is
      higher when the micro-organism is cultured under iron-restricted conditions. The
      study provides clues to understand the role of iron in the regulation of
      important activities of P. shigelloides.

PMID- 29380871
TI  - Extranodal natural killer/T-cell lymphoma, nasal type, in Senegal.
AB  - INTRODUCTION: The distribution of extranodal NK/T-cell lymphoma (ENKTCL) is
      highly inhomogeneous throughout the world. In Sub-Saharan Africa, despite the
      precocity of Epstein-Barr virus (EBV) infection and its endemicity, ENKTCL
      remains exceptionally reported. The purpose of this study was to report the
      epidemiological, clinical, paraclinical, and evolutionary characteristics of
      ENKTCL at the Aristide LeDantec University Hospital in Dakar, Senegal.
      METHODOLOGY: A 5-year retrospective review of all patients with
      histopathological, immunohistochemical, and in situ hybridization proven
      cutaneous lymphomas RESULTS: We collected seven cases corresponding to a
      frequency of 1.4 cases per year. ENKTCL accounted for 10.5% of all cutaneous
      lymphomas, ranking second after T-cell lymphomas. Men were predominantly affected
      (M : F ratio of 6), and the mean age was 38.5 years +/- 4.06. The mean time
      before consultation was 7.3 months. The lymphomas affected primarily the nasal
      cavity in five cases and the skin in two cases. At admission, six patients had
      nasal mucosa involvement, which was isolated in three cases, associated with
      cutaneous lesions in three cases and lymph node involvement in three cases. CD56
      was positive in only one case, and Eber transcribed RNA of EBV was expressed by
      in situ hybridization in all patients. DISCUSSION: To our knowledge, we have
      reported the first and largest series of ENKTCL in Sub-Saharan Africa. Our study
      shows an intermediate prevalence between that reported from Asia, Latin America,
      and the West. It was also noted a young age of patients, a prolonged diagnostic
      delay, a frequent negativity of CD56 marker, and a very poor prognosis of the
      disease in our region.

PMID- 29380872
TI  - Accurate costs of blood transfusion: a microcosting of administering blood
      products in the United Kingdom National Health Service.
AB  - BACKGROUND: In an environment of limited health care resources, it is crucial for
      health care systems which provide blood transfusion to have accurate and
      comprehensive information on the costs of transfusion, incorporating not only the
      costs of blood products, but also their administration. Unfortunately, in many
      countries accurate costs for administering blood are not available. Our study
      aimed to generate comprehensive estimates of the costs of administering
      transfusions for the UK National Health Service. STUDY DESIGN AND METHODS: A
      detailed microcosting study was used to cost two key inputs into transfusion:
      transfusion laboratory and nursing inputs. For each input, data collection forms
      were developed to capture staff time, equipment, and consumables associated with
      each step in the transfusion process. Costing results were combined with costs of
      blood product wastage to calculate the cost per unit transfused, separately for
      different blood products. Data were collected in 2014/15 British pounds and
      converted to US dollars. RESULTS: A total of 438 data collection forms were
      completed by 74 staff. The cost of administering blood was $71 (L49) per unit for
      red blood cells, $84 (L58) for platelets, $55 (L38) for fresh-frozen plasma, and
      $72 (L49) for cryoprecipitate. CONCLUSIONS: Blood administration costs add
      substantially to the costs of the blood products themselves. These are frequently
      incurred costs; applying estimates to the blood components supplied to UK
      hospitals in 2015, the annual cost of blood administration, excluding blood
      products, exceeds $175 (L120) million. These results provide more accurate
      estimates of the total costs of transfusion than those previously available.

PMID- 29380873
TI  - Annotation of gut bacterial taxonomic and functional diversity in Spodoptera
      litura and Spilosoma obliqua.
AB  - The insect gut has been the house of many taxonomically and physiologically
      diverse groups of microbial colonizers as symbionts and commensals, which are
      evolving to support the physiological requirement of insects. Lepidoptera is one
      of the important family of class hexapoda, comprising agriculture insect pest
      Spodoptera litura and Spilosoma obliqua. Information on gut microbiota and their
      functional role in these insects was meager to elucidate the wide-ranging
      survivalist mechanisms. In this context, we analyzed the composition, diversity
      and functional role of gut bacteria in S. litura and S. obliqua collected from
      soybean and sunflower crops, respectively, using Next Generation Sequencing of
      16S rRNA. A total of 3427 and 206 Operation Taxonomic Units (OTUs) were
      identified in S. litura and S. obliqua gut metagenome, respectively. Highest
      number of sequences were annotated to unclassified bacteria (34%), followed by
      Proteobacteria (27%), and Chlorobi (14%) in S. litura, while S. obliqua has
      significant representation of Firmicutes (48%), followed by Bacteroidetes (20%),
      and unclassified bacteria (11%). Functionality of both metagenomes revealed, high
      abundance of ammonia oxidizers (20.1 58.0%) followed by relative abundance of
      detoxifying processes - dehalogenation (17.4-41.2%) and aromatic hydrocarbons
      degradation (1.1-3.1%). This study highlights the significance of the inherent
      microbiome of two defoliators in shaping the metagenome for nutrition and
      detoxifying the chemical molecules, and opens an avenue for exploring role of
      insect gut bacteria in host selection, metabolic endurance of insecticides and
      synergistic or agonistic mechanisms inside gut of insects feeding on insect
      resistant biotech crops.

PMID- 29380874
TI  - Time-lagged effects of weather on plant demography: drought and Astragalus
      scaphoides.
AB  - Temperature and precipitation determine the conditions where plant species can
      occur. Despite their significance, to date, surprisingly few demographic field
      studies have considered the effects of abiotic drivers. This is problematic
      because anticipating the effect of global climate change on plant population
      viability requires understanding how weather variables affect population
      dynamics. One possible reason for omitting the effect of weather variables in
      demographic studies is the difficulty in detecting tight associations between
      vital rates and environmental drivers. In this paper, we applied Functional
      Linear Models (FLMs) to long-term demographic data of the perennial wildflower,
      Astragalus scaphoides, and explored sensitivity of the results to reduced amounts
      of data. We compared models of the effect of average temperature, total
      precipitation, or an integrated measure of drought intensity (standardized
      precipitation evapotranspiration index, SPEI), on plant vital rates. We found
      that transitions to flowering and recruitment in year t were highest if
      winter/spring of year t was wet (positive effect of SPEI). Counterintuitively, if
      the preceding spring of year t - 1 was wet, flowering probabilities were
      decreased (negative effect of SPEI). Survival of vegetative plants from t - 1 to
      t was also negatively affected by wet weather in the spring of year t - 1 and,
      for large plants, even wet weather in the spring of t - 2 had a negative effect.
      We assessed the integrated effect of all vital rates on life history performance
      by fitting FLMs to the asymptotic growth rate, log(lambdat). Log(lambdat) was
      highest if dry conditions in year t - 1 were followed by wet conditions in the
      year t. Overall, the positive effects of wet years exceeded their negative
      effects, suggesting that increasing frequency of drought conditions would reduce
      population viability of A. scaphoides. The drought signal weakened when reducing
      the number of monitoring years. Substituting space for time did not recover the
      weather signal, probably because the weather variables varied little between
      sites. We detected the SPEI signal when the analysis included data from two sites
      monitored over 20 yr (2 * 20 observations), but not when analyzing data from four
      sites monitored over 10 yr (4 * 10 observations).

PMID- 29380875
TI  - The value of cell-free DNA for molecular pathology.
AB  - Over the past decade, advances in molecular biology and genomics techniques have
      revolutionized the diagnosis and treatment of cancer. The technological advances
      in tissue profiling have also been applied to the study of cell-free nucleic
      acids, an area of increasing interest for molecular pathology. Cell-free nucleic
      acids are released from tumour cells into the surrounding body fluids and can be
      assayed non-invasively. The repertoire of genomic alterations in circulating
      tumour DNA (ctDNA) is reflective of both primary tumours and distant metastatic
      sites, and ctDNA can be sampled multiple times, thereby overcoming the
      limitations of the analysis of single biopsies. Furthermore, ctDNA can be sampled
      regularly to monitor response to treatment, to define the evolution of the tumour
      genome, and to assess the acquisition of resistance and minimal residual disease.
      Recently, clinical ctDNA assays have been approved for guidance of therapy, which
      is an exciting first step in translating cell-free nucleic acid research tests
      into clinical use for oncology. In this review, we discuss the advantages of cell
      free nucleic acids as analytes in different body fluids, including blood plasma,
      urine, and cerebrospinal fluid, and their clinical applications in solid tumours
      and haematological malignancies. We will also discuss practical considerations
      for clinical deployment, such as preanalytical factors and regulatory
      requirements. Copyright (c) 2018 Pathological Society of Great Britain and
      Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29380876
TI  - IgE-expressing memory B cells and plasmablasts are increased in blood of children
      with asthma, food allergy, and atopic dermatitis.
AB  - Despite the critical role of soluble IgE in the pathology of IgE-mediated
      allergic disease, little is known about abnormalities in the memory B cells and
      plasma cells that produce IgE in allergic patients. We here applied a flow
      cytometric approach to cross-sectionally study blood IgE+ memory B cells and
      plasmablasts in 149 children with atopic dermatitis, food allergy, and/or asthma
      and correlated these to helper T(h)2 cells and eosinophils. Children with
      allergic disease had increased numbers of IgE+CD27- and IgE+CD27+ memory B cells
      and IgE+ plasmablasts, as well as increased numbers of eosinophils and Th2 cells.
      IgE+ plasmablast numbers correlated positively with Th2 cell numbers. These
      findings open new possibilities for diagnosis and monitoring of treatment in
      patients with allergic diseases.

PMID- 29380878
TI  - Flat-topped papules on the face of a young boy.

PMID- 29380879
TI  - Emergent buffering balances evolvability and robustness in the evolution of
      phenotypic flexibility.
AB  - Evolution of adaptive phenotypic flexibility requires a system that can
      dynamically restore and update a functional phenotype in response to
      environmental change. The architecture of such a system evolves under the
      conflicting demands of versatility and robustness, and resolution of these
      demands should be particularly evident in organisms that require external inputs
      for reiterative trait production within a generation, such as in metabolic
      networks that underlie yearly acquisition of diet-dependent coloration in birds.
      Here, we show that a key structural feature of carotenoid networks-redundancy of
      biochemical pathways-enables these networks to translate variable environmental
      inputs into consistent phenotypic outcomes. We closely followed life-long changes
      in structure and utilization of metabolic networks in a large cohort of free
      living birds and found that greater individual experience with dietary change
      between molts leads to wider occupancy of the metabolic network and progressive
      accumulation of redundant pathways in a functionally active network. This
      generated a regime of emergent buffering whereby greater dietary experience was
      mechanistically linked to greater robustness of resulting traits and an
      increasing ability to retain and implement previous adaptive solutions. Thus,
      experience-related buffering links evolvability and robustness in carotenoid
      metabolizing networks and we argue that this mechanistic principle facilitates
      the evolution of phenotypic flexibility.

PMID- 29380877
TI  - The mental health continuum-short form: The structure and application for cross
      cultural studies-A 38 nation study.
AB  - OBJECTIVE: The Mental Health Continuum-Short Form (MHC-SF) is a brief scale
      measuring positive human functioning. The study aimed to examine the factor
      structure and to explore the cross-cultural utility of the MHC-SF using bifactor
      models and exploratory structural equation modelling. METHOD: Using multigroup
      confirmatory analysis (MGCFA) we examined the measurement invariance of the MHC
      SF in 38 countries (university students, N = 8,066; 61.73% women, mean age 21.55
      years). RESULTS: MGCFA supported the cross-cultural replicability of a bifactor
      structure and a metric level of invariance between student samples. The average
      proportion of variance explained by the general factor was high (ECV = .66),
      suggesting that the three aspects of mental health (emotional, social, and
      psychological well-being) can be treated as a single dimension of well-being.
      CONCLUSION: The metric level of invariance offers the possibility of comparing
      correlates and predictors of positive mental functioning across countries;
      however, the comparison of the levels of mental health across countries is not
      possible due to lack of scalar invariance. Our study has preliminary character
      and could serve as an initial assessment of the structure of the MHC-SF across
      different cultural settings. Further studies on general populations are required
      for extending our findings.

PMID- 29380880
TI  - Validation of a model of feline ureteral obstruction as a tool for teaching
      microsurgery to veterinary surgeons.
AB  - OBJECTIVE: To assess the content and face validity of a model of an obstructed
      feline ureter as a tool for teaching ureteral microsurgery. STUDY DESIGN:
      Prospective, experimental study. SAMPLE POPULATION: Seven expert and 11 novice
      microsurgeons. METHODS: The model was created from latex rubber with an inner
      diameter of 0.8 mm and an outer diameter of 5 mm. The "ureter" was created with
      an inner compartment, a thin wall, and a soft, outer layer mimicking periureteral
      fat. A "ureterolith" 0.8-1.2 mm in diameter was placed inside the inner
      compartment by using a blunt-tipped cannula. A standardized "ureterotomy" was
      performed by 7 expert and 11 novice microsurgeons. Both groups completed
      questionnaires evaluating the content and face validity of the model using
      subjective measures and a 5-point Likert scale. Reliability was analysed by
      calculation of Cronbach's alpha for all questions to ensure alpha >= .7. The
      median responses to each question were compared between groups with a
      nonparametric independent samples median test. P < .05 was considered
      significant. RESULTS: The Cronbach's alpha for the experts and the novices for
      content validity questions was .7 and .9, respectively, and for the face validity
      questions it was .7 and .8, respectively. The model was rated to have excellent
      content validity and very good face validity. CONCLUSION AND IMPACT: The model
      elicited positive responses from expert and novice microsurgeons and can be
      recommended as a tool for teaching ureteral microsurgery. A model validated by
      face and content measures should next be scrutinized by determination of
      construct, concurrent, and predictive validity by using objective measures.

PMID- 29380881
TI  - Race and diversity in U.S. Biological Anthropology: A decade of AAPA initiatives.
AB  - Biological Anthropology studies the variation and evolution of living humans, non
      human primates, and extinct ancestors and for this reason the field should be in
      an ideal position to attract scientists from a variety of backgrounds who have
      different views and experiences. However, the origin and history of the
      discipline, anecdotal observations, self-reports, and recent surveys suggest the
      field has significant barriers to attracting scholars of color. For a variety of
      reasons, including quantitative research that demonstrates that diverse groups do
      better science, the discipline should strive to achieve a more diverse
      composition. Here we discuss the background and underpinnings of the current and
      historical dearth of diversity in Biological Anthropology in the U.S.
      specifically as it relates to representation of minority and underrepresented
      minority (URM) (or racialized minority) scholars. We trace this lack of diversity
      to underlying issues of recruitment and retention in the STEM sciences generally,
      to the history of Anthropology particularly around questions of race-science, and
      to the absence of Anthropology at many minority-serving institutions, especially
      HBCUs, a situation that forestalls pathways to the discipline for many minority
      students. The AAPA Committee on Diversity (COD) was conceived as a means of
      assessing and improving diversity within the discipline, and we detail the
      history of the COD since its inception in 2006. Prior to the COD there were no
      systematic AAPA efforts to consider ethnoracial diversity in our ranks and no
      programming around questions of diversity and inclusion. Departmental survey data
      collected by the COD indicate that undergraduate majors in Biological
      Anthropology are remarkably diverse, but that the discipline loses these scholars
      between undergraduate and graduate school and systematically up rank. Our
      analysis of recent membership demographic survey data (2014 and 2017) shows
      Biological Anthropology to have less ethnoracial diversity than even the
      affiliated STEM disciplines of Biology and Anatomy; nearly 87% of AAPA members in
      the United States identify as white and just 7% as URM scholars. These data also
      suggest that the intersection of race and gender significantly influence
      scholarly representation. In response to these data, we describe a substantial
      body of programs that have been developed by the COD to improve diversity in our
      ranks. Through these programs we identify principal concerns that contribute to
      the loss of scholars of color from the discipline at different stages in their
      careers, propose other directions that programming for recruitment should take,
      and discuss the beginnings of how to develop a more inclusive discipline at all
      career stages.

PMID- 29380882
TI  - Participation, representation, and shared experiences of women scholars in
      biological anthropology.
AB  - American Association of Physical Anthropologists (AAPA) membership surveys from
      1996 and 1998 revealed significant gender disparities in academic status. A 2014
      follow-up survey showed that gender equality had improved, particularly with
      respect to the number of women in tenure-stream positions. However, although
      women comprised 70% of AAPA membership at that time, the percentage of women full
      professors remained low. Here, we continue to consider the status of women in
      biological anthropology by examining the representation of women through a
      quantitative analysis of their participation in annual meetings of the AAPA
      during the past 20 years. We also review the programmatic goals of the AAPA
      Committee on Diversity Women's Initiative (COD-WIN) and provide survey results of
      women who participated in COD-WIN professional development workshops. Finally, we
      examine the diversity of women's career paths through the personal narratives of
      14 women biological anthropologists spanning all ranks from graduate student to
      Professor Emeritus. We find that over the past 20 years, the percentage of women
      first authors of invited symposia talks has increased, particularly in the sub
      disciplines of bioarchaeology, genetics, and paleoanthropology. The percentage of
      women first authors on contributed talks and posters has also increased. However,
      these observed increases are still lower than expected given the percentage of
      graduate student women and women at the rank of assistant and associate
      professor. The personal narratives highlight first-hand the impact of mentoring
      on career trajectory, the challenges of achieving work-life satisfaction, and
      resilience in the face of the unexpected. We end with some suggestions for how to
      continue to improve equality and equity for women in biological anthropology.

PMID- 29380883
TI  - What have we been looking at? A call for consistency in studies of primate
      vigilance.
AB  - Vigilance functions to detect threats. In primates, these threats emerge from
      both predators and conspecifics, but a host of other social, demographic, and
      ecological factors have been shown to influence primate vigilance patterns. The
      primate vigilance literature is thus characterized by considerable variation in
      findings, with inconsistent or contradictory results reported not only across
      different species but also within species and populations across studies. Some of
      this variation could emerge from fundamental differences in the methods employed,
      making comparisons across species and groups challenging. Furthermore,
      identifying consistent behavioral markers for the state of vigilance appears to
      have proved challenging in primates, leading to a range of definitions being
      developed. Deviation at this level leads directly into concomitant variation at
      the level of sampling methodologies. As a result, the primate vigilance
      literature currently presents a diverse series of approaches to exploring subtly
      different behaviors and phenomena. This review calls for a greater consistency in
      studying vigilance, with the aim of encouraging future research to follow similar
      principles leading to more comparable results. Identifying whether an animal is
      in a vigilant state is challenging for most field researchers; identifying and
      recording a more general behavior of "looking" should though be more achievable.
      Experimental approaches could then be employed to understand the compatibility
      "looking" has with predator detection (and other threats) in individual study
      systems. The outcome of this approach will allow researchers to understand the
      key determinants of looking in their study groups and explore threat detection
      probabilities given an individual or group's relative level of looking.

PMID- 29380884
TI  - Single (sub)species then and now: An examination of the nonracial perspective of
      C. Loring Brace.
AB  - C. Loring Brace's writings on the concept of race have been among the most
      influential within anthropology. A review of the development of Brace's
      perspective on race shows that his philosophical approaches to fossil and modern
      human variation are consistent and integrated. Brace's views on race are compared
      with those of Ashley Montagu and Frank Livingstone, who also proposed eliminating
      "race" from anthropology, and with those of Stanley Garn and Alice Brues, who
      accepted "racial" subdivisions of humans. Carleton Coon's writings are more
      divergent; the aftermath of the publication of his Origin of Races highlights
      significant political tensions of the 1960s that intersected with scientific
      changes in anthropology emanating from the Evolutionary Synthesis. Recent
      forensic and "no race" positions are compared to explore their differences and
      the possibility of reconciliation, and the role of Brace and others in combating
      proposals of intellectual differences among human groups is discussed. While a
      spectrum of anthropological opinion regarding race exists, the commonalities are
      sufficient to allow valuable, united commentary emphasizing the complexity of
      modern human cultural and biological variation.

PMID- 29380885
TI  - Preface 2018 Yearbook.

PMID- 29380886
TI  - The behavioral genetics of nonhuman primates: Status and prospects.
AB  - The complexity and diversity of primate behavior have long attracted the
      attention of ethologists, psychologists, behavioral ecologists, and
      neuroscientists. Recent studies have advanced our understanding of the nature of
      genetic influences on differences in behavior among individuals within species. A
      number of analyses have focused on the genetic analysis of behavioral reactions
      to specific experimental tests, providing estimates of the degree of genetic
      control over reactivity, and beginning to identify the genes involved.
      Substantial progress is also being made in identifying genetic factors that
      influence the structure and function of the primate brain. Most of the published
      studies on these topics have examined either cercopithecines or chimpanzees,
      though a few studies have addressed these questions in other primate species. One
      potentially important line of research is beginning to identify the epigenetic
      processes that influence primate behavior, thus revealing specific cellular and
      molecular mechanisms by which environmental experiences can influence gene
      expression or gene function relevant to behavior. This review summarizes many of
      these studies of non-human primate behavioral genetics. The primary focus is on
      analyses that address the nature of the genes and genetic processes that affect
      differences in behavior among individuals within non-human primate species.
      Analyses of between species differences and potential avenues for future research
      are also discussed.

PMID- 29380887
TI  - Developments in development: What have we learned from primate locomotor
      ontogeny?
AB  - The importance of locomotion to evolutionary fitness has led to extensive study
      of primate locomotor behavior, morphology and ecology. Most previous research has
      focused on adult primates, but in the last few decades, increased attention to
      locomotor development has provided new insights toward our broader understanding
      of primate adaptation and evolution. Here, we review the contributions of this
      body of work from three basic perspectives. First, we assess possible
      determinants on the timing of locomotor independence, an important life history
      event. Significant influences on timing of locomotor independence include adult
      female body mass, age at weaning, and especially relative brain size, a
      significant predictor of other primate life history variables. Additionally, we
      found significant phylogenetic differences in the timing of locomotor
      independence, even accounting for these influences. Second, we discuss how
      structural aspects of primate growth may enhance the locomotor performance and
      safety of young primates, despite their inherent neuromotor and musculoskeletal
      limitations. For example, compared to adults, growing primates have greater
      muscle mechanical advantage, greater bone robusticity, and larger extremities
      with relatively long digits. Third, focusing on primate quadrupedalism, we
      provide examples that illustrate how ontogenetic transitions in morphology and
      locomotion can serve as a model system for testing broader principles underlying
      primate locomotor biomechanics. This approach has led to a better understanding
      of the key features that contribute to primates' stride characteristics, gait
      patterns, limb force distribution, and limb postures. We have learned a great
      deal from the study of locomotor ontogeny, but there is much left to explore. We
      conclude by offering guidelines for future research, both in the laboratory and
      the field.

PMID- 29380888
TI  - Sharing the burden: A neutral approach to socioecological theory.
AB  - OBJECTIVE: The socioecological model (SEM) is a popular collection of
      controversial models purporting to explain mating systems in terms of ecological
      and social parameters. Despite its guise of objectivity, several of its
      hypotheses assume Victorian gender stereotypes of active, competing males
      heedlessly sowing their seeds, and cautious, passive females, imprisoned by
      greater costs of reproduction and their consequent resource?dependence. METHODS:
      We enter this debate by taking a previously neglected explanatory approach
      borrowed from species theory. According to the Recognition Concept of sexual
      species, the unit of reproductive success/fitness is irreducible to fewer than
      two integrated subparts (minimally a male and a female). Phyletic changes in
      mating systems logically effect changes in fertilization systems, leading to
      reproductive isolation. We take our primary assumption of the average equivalence
      of female and male contributions to successful reproduction from the writings of
      the natural philosopher, Antoinette Blackwell. RESULTS: We revisit the SEM with
      its contradictions and extrapolations, and develop a gender?neutral alternative
      hypothesis termed Specific?Mate Contact (SMC), centered on two fundamental mating
      strategies: sexual animals may behave as synchronous mate?attractors or
      asynchronous mate?seekers, generating four possible mating system combinations
      (monogamy: two attractors; promiscuity: two seekers; polygyny: male attractor and
      female seeker; polyandry: female attractor and male seeker). CONCLUSIONS: Our
      approach predicts all known primate mating systems using a neutral (non?sexist)
      principle. The approach is also neutral in the sense that it does not invoke
      either competition or cooperation: fertilization success is considered a
      posteriori and males and females are co?adapted to this end rather than
      cognitively cooperative.

PMID- 29380889
TI  - Early Homo and the role of the genus in paleoanthropology.
AB  - The history of the discovery of early fossils attributed to the genus Homo has
      been contentious, with scholars disagreeing over the generic assignment of
      fossils proposed as members of our genus. In this manuscript I review the history
      of discovery and debate over early Homo and evaluate the various taxonomic
      hypotheses for the genus. To get a sense of how hominin taxonomy compares to
      taxonomic practice outside paleoanthropology, I compare the diversity of Homo to
      genera in other vertebrate clades. Finally, I propose a taxonomic model that hews
      closely to current models for hominin phylogeny and is consistent with taxonomic
      practice across evolutionary biology.

PMID- 29380890
TI  - Kidney allograft subclinical rejection modulates systemic inflammation measured
      by C-reactive protein at 1 year after transplantation.
AB  - Kidney allograft inflammation is associated with proinflammatory modifications of
      peripheral blood mononuclear cells, suggesting that renal inflammation
      contributes to systemic inflammation. Thus, the aim of this study was to evaluate
      the relationship between subclinical inflammation in surveillance biopsies
      performed at 1 year and systemic inflammation assessed by C-reactive protein
      (CRP) levels at the time of biopsy. We analyzed 544 surveillance biopsies
      performed at 1 year that were classified as normal (n = 368), borderline (n =
      148), or subclinical rejection (SCR) (n = 28). CRP levels were divided into
      quartiles. Patients in 1st, 2nd, and 3rd quartile were classified as low CRP (n =
      408) and patients in the 4th quartile as high CRP (n = 136). Univariate analysis
      showed that the proportion of patients with SCR was higher in the high CRP group
      (10.3% vs 3.4%, P = 0.0067). Multivariate analysis showed that independent
      predictors of high CRP were body mass index (odds ratio [OR] 1.072 and 95%
      confidence interval [CI] 1.027-1.119), a positive urine culture at the day of the
      biopsy (OR 2.760 and 95% CI 1.205-6.323), and the presence of SCR at 1-year
      surveillance biopsy (OR 7.260 and 95% CI 3.530-14.935). In summary, we describe
      that subclinical acute rejection constitutes an independent predictor of systemic
      inflammation as measured by CRP.

PMID- 29380891
TI  - Extrusion-Based 3D Printing of Hierarchically Porous Advanced Battery Electrodes.
AB  - A highly porous 2D nanomaterial, holey graphene oxide (hGO), is synthesized
      directly from holey graphene powder and employed to create an aqueous 3D
      printable ink without the use of additives or binders. Stable dispersions of
      hydrophilic hGO sheets in water (~100 mg mL-1 ) can be readily achieved. The
      shear-thinning behavior of the aqueous hGO ink enables extrusion-based printing
      of fine filaments into complex 3D architectures, such as stacked mesh structures,
      on arbitrary substrates. The freestanding 3D printed hGO meshes exhibit trimodal
      porosity: nanoscale (4-25 nm through-holes on hGO sheets), microscale (tens of
      micrometer-sized pores introduced by lyophilization), and macroscale (<500 um
      square pores of the mesh design), which are advantageous for high-performance
      energy storage devices that rely on interfacial reactions to promote full active
      site utilization. To elucidate the benefit of (nano)porosity and structurally
      conscious designs, the additive-free architectures are demonstrated as the first
      3D printed lithium-oxygen (Li-O2 ) cathodes and characterized alongside 3D
      printed GO-based materials without nanoporosity as well as nanoporous 2D vacuum
      filtrated films. The results indicate the synergistic effect between 2D
      nanomaterials, hierarchical porosity, and overall structural design, as well as
      the promise of a freeform generation of high-energy-density battery systems.

PMID- 29380892
TI  - Masseteric cooptation and crossfacial nerve grafting: Is it still applicable 22
      months after the onset of facial palsy?
AB  - BACKGROUND: Eighteen months is usually considered the cutoff time within which
      recovery of the mimic muscle remains possible using facial nerve cooptation. Few
      reports on the use of cooptation after this interval have appeared. Purpose of
      this study is to investigate the feasibility of this procedure also after 22
      months. METHODS: Six patients treated via crossfacial nerve grafting between
      healthy and paralyzed middle and middle-upper facial nerve branches and
      masseteric cooptation of the main trunk of the paralyzed facial nerve between 20
      and 24 months after the onset of palsy were analyzed. Population consisted of two
      males and four females ages 8-42 years (mean 24 years). Facial palsy developed
      after acoustic neuroma resection in three patients, after the removal of a
      cerebellopontine angle astrocytoma in one, and as a consequence of Bell's palsy
      or cerebral hemorrhage in the other two (one each). House-Brackman and Sunnybrook
      clinical evaluation systems and FDI questionnaire were used to assess results.
      RESULTS: House-Brackman scores changed from VI before the operation for all
      patients to II for two patients and III for four patients. Sunnybrook scores were
      0-10 before the operation, but 62-84 at the last visit. Mean FDI scores moved
      from 24 to 38.5 meaning a statistical high significant improvement (P < .01).
      CONCLUSIONS: Masseteric/crossfacial nerve grafting is feasible for patients with
      palsies 20-24 months in duration, affording satisfactory functional and esthetic
      results and a dramatic improvement in quality of life.

PMID- 29380893
TI  - Emergency Department Patient Perceptions of Transvaginal Ultrasound for
      Complications of First-Trimester Pregnancy.
AB  - OBJECTIVES: Emergency department (ED) transvaginal ultrasound (US) is underused
      in clinical practice. This study assessed pregnant women's perceptions of ED
      transvaginal US in terms of pain, embarrassment, anxiety, and willingness to
      receive the procedure. Secondary variables include physicians' perceptions of
      patients' experiences. METHODS: Women undergoing US examinations for
      complications of first-trimester pregnancy were prospectively surveyed before any
      US and after ED and/or radiology transvaginal US. Patients' and physicians'
      assessments of pain, embarrassment, and anxiety were measured with visual analog
      scales (0-100). RESULTS: A total of 398 women were enrolled. In the pre-US
      survey, the median anxiety score was 14 (interquartile range, 3-51), and 96% of
      patients were willing to have an ED transvaginal US if necessary. Of those who
      had ED transvaginal US, 96% would agree to have another examination. Patients
      reported minimal pain/embarrassment, and there was no difference if performed in
      the ED versus radiology (median pain, 11.5 versus 13; P = .433; median
      embarrassment, 7 versus 4; P = .345). Of the 48 who had both ED and radiology
      transvaginal US, 85% thought the ED transvaginal US was worthwhile. Physicians
      accurately assessed patient's embarrassment and pain (mean differences, 3.5 and 
      1.9, respectively; P > .25 for both); however, they overestimated them relative
      to the pelvic examination (mean difference for embarrassment, 12.8; P < .0001;
      pain, 8.0; P = .01). CONCLUSIONS: Pregnant ED patients report low levels of
      anxiety, pain, and embarrassment, and after ED transvaginal US, 96% would agree
      to have the examination again. There is no difference in pain/embarrassment
      between ED and radiology transvaginal US. Emergency department physicians
      accurately assessed patients' pain and embarrassment with ED transvaginal US but
      overestimated them compared to the pelvic examination.

PMID- 29380894
TI  - The 100 most cited articles on oral cancer.
AB  - BACKGROUND: Citations analysis is one of the most widely used bibliometric tools
      to evaluate the academic importance of a study in a specific area of knowledge.
      The objective of this study was to identify the 100 most cited articles on oral
      cancer and to analyse their principal characteristics. METHODS: We performed a
      literature search in the Web of Science database using the Science Citation Index
      Expanded tool to determine the number of citations of all articles on oral cancer
      identified up to 10 August 2017. The 100 most referenced articles were then
      selected, and the following information was gathered: ranking based on the number
      of citations; citation density; citations in Scopus; number and names of the
      authors; language and year of publication; country and institution of origin;
      financial support; journal of publication, with its impact factor, category and
      quartile; type of research; evidence level; and area of study. RESULTS: The
      number of citations of the 100 articles varied from 1959 to 165, and the number
      of authors varied from a single author to 23. The oldest article was from 1948,
      and the most recent was from 2013. All the studies were published in English, the
      majority (56%) was from the United States, and 80% were published in journals in
      the first quartile. CONCLUSIONS: The majority of articles were of studies that
      had received financial support, were published in journals with a high impact
      factor and were focussed on the aetiology and pathogenesis of oral cancer.

PMID- 29380895
TI  - Use of polyphenols as a strategy to prevent bond degradation in the dentin-resin
      interface.
AB  - This study evaluated the effect of dentin pretreatment with the polyphenols
      quercetin and resveratrol on the resin-dentin microtensile bonding strength
      (MUTBS) and collagen fibrils stability of the adhesive interface. Different
      concentrations (100, 250, 500, or 1,000 MUg ml-1 ) of quercetin or resveratrol,
      or a mixture of quercetin and resveratrol (3:1, 1:1, 1:3; vol:vol), as well as
      distilled water or 2% chlorhexidine digluconate, were applied to etched dentin.
      Then, a two-step etch-and-rinse adhesive was applied followed by composite
      restoration. Measurements of resin-dentin MUTBS were made after 1 and 120 d. The
      stability of collagen fibrils in the hybrid layer was evaluated using
      transmission electron microscopy. The Student's t-test and two-way factorial
      anova with Tukey's test were used to analyze the effects of dentin pretreatment
      and storage time on MUTBS values. Comparisons between MUTBS measurements made on
      1 and 120 d showed that resveratrol had the best performance, with significantly
      higher MUTBS values after 120 d for all concentrations of resveratrol tested.
      Quercetin pretreatment resulted in a significant rise of MUTBS when used at
      concentrations of 100 and 500 MUg ml-1 . Quercetin + resveratrol at the ratio of
      1:1 performed better than when used at ratios of either 3:1 or 1:3. Resveratrol
      might represent a potential approach to achieve desirable bonding stability and
      reduce the frequent replacement of composite restorations.

PMID- 29380896
TI  - Auxetic Mechanical Metamaterials to Enhance Sensitivity of Stretchable Strain
      Sensors.
AB  - Stretchable strain sensors play a pivotal role in wearable devices, soft
      robotics, and Internet-of-Things, yet these viable applications, which require
      subtle strain detection under various strain, are often limited by low
      sensitivity. This inadequate sensitivity stems from the Poisson effect in
      conventional strain sensors, where stretched elastomer substrates expand in the
      longitudinal direction but compress transversely. In stretchable strain sensors,
      expansion separates the active materials and contributes to the sensitivity,
      while Poisson compression squeezes active materials together, and thus
      intrinsically limits the sensitivity. Alternatively, auxetic mechanical
      metamaterials undergo 2D expansion in both directions, due to their negative
      structural Poisson's ratio. Herein, it is demonstrated that such auxetic
      metamaterials can be incorporated into stretchable strain sensors to
      significantly enhance the sensitivity. Compared to conventional sensors, the
      sensitivity is greatly elevated with a 24-fold improvement. This sensitivity
      enhancement is due to the synergistic effect of reduced structural Poisson's
      ratio and strain concentration. Furthermore, microcracks are elongated as an
      underlying mechanism, verified by both experiments and numerical simulations.
      This strategy of employing auxetic metamaterials can be further applied to other
      stretchable strain sensors with different constituent materials. Moreover, it
      paves the way for utilizing mechanical metamaterials into a broader library of
      stretchable electronics.

PMID- 29380897
TI  - Infrared Organic Light-Emitting Diodes with Carbon Nanotube Emitters.
AB  - While organic light-emitting diodes (OLEDs) covering all colors of the visible
      spectrum are widespread, suitable organic emitter materials in the near-infrared
      (nIR) beyond 800 nm are still lacking. Here, the first OLED based on single
      walled carbon nanotubes (SWCNTs) as the emitter is demonstrated. By using a
      multilayer stacked architecture with matching charge blocking and charge
      transport layers, narrow-band electroluminescence at wavelengths between 1000 and
      1200 nm is achieved, with spectral features characteristic of excitonic and
      trionic emission of the employed (6,5) SWCNTs. Here, the OLED performance is
      investigated in detail and it is found that local conduction hot-spots lead to
      pronounced trion emission. Analysis of the emissive dipole orientation shows a
      strong horizontal alignment of the SWCNTs with an average inclination angle of
      12.9 degrees  with respect to the plane, leading to an exceptionally high
      outcoupling efficiency of 49%. The SWCNT-based OLEDs represent a highly
      attractive platform for emission across the entire nIR.

PMID- 29380898
TI  - Cytoprotective effect of flavonoid-induced autophagy on bisphosphonate mediated
      cell death in osteoblast.
AB  - With rapid economic growth and further developments in medical science, the entry
      into the aging population is currently increasing, as is the number of patients
      with metabolic diseases, such as hypertension, hyperlipidemia, heart disease, and
      diabetes. The current treatments for metabolic bone diseases, which are also on
      the rise, cause negative side effects. Bisphosphonates, which are used to treat
      osteoporosis, inhibit the bone resorption ability of osteoclasts and during
      prolonged administration, cause bisphosphonate-related osteonecrosis of the jaw
      (BRONJ). Numerous studies have shown the potential role of natural plant products
      as flavonoids in the protection against osteoporosis and in the influence of bone
      remodeling. Autophagy occurs after the degradation of cytoplasmic components
      within the lysosome and serves as an essential cytoprotective response to
      pathologic stress caused by certain diseases. In the present study, we
      hypothesized that the cytoprotective effects of flavonoids might be related to
      those associated with autophagy, an essential cytoprotective response to the
      pathologic stress caused by certain diseases, in osteoblasts. We demonstrated the
      cytoprotective effect of flavonoid-induced autophagy against the toxicity of
      zoledronate and the induction of autophagy by flavonoids to support osteogenic
      transcription factors, leading to osteoblast differentiation and bone formation.
      Further studies are necessary to clarify the connections between autophagy and
      osteogenesis. It would be helpful to shed light on methodological challenges
      through molecular biological studies and new animal models. The findings of the
      current study may help to delineate the potential role of flavonoids in the
      treatment of metabolic bone disease.

PMID- 29380899
TI  - Benzoate-Induced High-Nuclearity Silver Thiolate Clusters.
AB  - Compared with the well-known anion-templated effects in shaping silver thiolate
      clusters, the influence from the organic ligands in the outer shell is still
      poorly understood. Herein, three new benzoate-functionalized high-nuclearity
      silver(I) thiolate clusters are isolated and characterized for the first time in
      the presence of diverse anion templates such as S2- , alpha-[Mo5 O18 ]6- , and
      MoO42- . Single-crystal X-ray analysis reveals that the nuclearities of the three
      silver clusters (SD/Ag28, SD/Ag29, SD/Ag30) vary from 32 to 38 to 78 with co
      capped tBuS- and benzoate ligands on the surface. SD/Ag28 is a turtle-like
      cluster comprising a Ag29 shell caging a Ag3 S3 trigon in the center, whereas
      SD/Ag29 is a prolate Ag38 sphere templated by the alpha-[Mo5 O18 ]6- anion. Upon
      changing from benzoate to methoxyl-substituted benzoate, SD/Ag30 is isolated as a
      very complicated core-shell spherical cluster composed of a Ag57 shell and a vase
      like Ag21 S13 core. Four MoO42- anions are arranged in a supertetrahedron and
      located in the interstice between the core and shell. Introduction of the bulky
      benzoate changes elaborately the nuclearity and arrangements of silver polygons
      on the shell of silver clusters, which is exemplified by comparing SD/Ag28 and a
      known similar silver thiolate cluster. The three new clusters emit luminescence
      in the near-infrared (NIR) region and show different thermochromic luminescence
      properties. This work presents a flexible approach to synthetic studies of high
      nuclearity silver clusters decorated by different benzoates, and structural
      modulations are also achieved.

PMID- 29380901
TI  - The influence of agents differentiating HL-60 cells toward granulocyte-like cells
      on their ability to release neutrophil extracellular traps.
AB  - Studies on neutrophil extracellular traps (NETs) are challenging as neutrophils
      live shortly and easily become activated. Thus, availability of a cell line model
      closely resembling the functions of peripheral blood neutrophils would be
      advantageous. Our purpose was to find a compound that most effectively
      differentiates human promyelocytic leukemia (HL-60) cells toward granulocyte-like
      cells able to release NETs. HL-60 cells were differentiated with all-trans
      retinoic acid (ATRA), dimethyl sulfoxide (DMSO) or dimethylformamide (DMF) and
      stimulated with phorbol 12-myristate 13-acetate (PMA) or calcium ionophore A23187
      (CI). Cell differentiation, phagocytosis and calcium influx were analyzed by flow
      cytometry. Reactive oxygen species production and NETs release were measured
      fluorometrically and analyzed microscopically. LC3-II accumulation and histone 3
      citrullination were analyzed by western blot. ATRA most effectively
      differentiated HL-60 cells toward granulocyte-like cells. ATRA-dHL-60 cells
      released NETs only upon PMA stimulation, DMSO-dHL-60 cells only post CI
      stimulation, while DMF-dHL-60 cells formed NETs in response to both stimuli.
      Oxidative burst was induced in ATRA-, DMSO- and DMF-dHL-60 cells post PMA
      stimulation and only in DMF-dHL-60 cells post CI stimulation. Increased histone 3
      citrullination was observed in stimulated DMSO- and DMF-, but not in ATRA-dHL-60
      cells. The calcium influx was diminished in ATRA-dHL-60 cells. Significant
      increase in autophagosomes formation was observed only in PMA-stimulated DMF-dHL
      60 cells. Phagocytic index was higher in ATRA-dHL-60 cells than in control, DMSO-
      and DMF-dHL-60 cells. We conclude that ATRA, DMSO and DMF differentiate HL-60 in
      different mechanisms. DMF is the best stimulus for HL-60 cell differentiation for
      NETs studies.

PMID- 29380900
TI  - Integrin alpha V beta 3 targeted dendrimer-rapamycin conjugate reduces fibroblast
      mediated prostate tumor progression and metastasis.
AB  - Therapeutic strategies targeting both cancer cells and associated cells in the
      tumor microenvironment offer significant promise in cancer therapy. We previously
      reported that generation 5 (G5) dendrimers conjugated with cyclic-RGD peptides
      target cells expressing integrin alpha V beta 3. In this study, we report a novel
      dendrimer conjugate modified to deliver the mammalian target of rapamycin (mTOR)
      inhibitor, rapamycin. In vitro analyses demonstrated that this drug conjugate, G5
      FI-RGD-rapamycin, binds to prostate cancer (PCa) cells and fibroblasts to inhibit
      mTOR signaling and VEGF expression. In addition, G5-FI-RGD-rapamycin inhibits
      mTOR signaling in cancer cells more efficiently under proinflammatory conditions
      compared to free rapamycin. In vivo studies established that G5-FI-RGD-rapamycin
      significantly inhibits fibroblast-mediated PCa progression and metastasis. Thus,
      our results suggest the potential of new rapamycin-conjugated multifunctional
      nanoparticles for PCa therapy.

PMID- 29380902
TI  - Probing the striatal dopamine system for a putative neuroprotective effect of
      deep brain stimulation in Parkinson's disease.

PMID- 29380903
TI  - Iron as a therapeutic target for Parkinson's disease.

PMID- 29380904
TI  - Deep Blue Phosphorescent Organic Light-Emitting Diodes with CIEy Value of 0.11
      and External Quantum Efficiency up to 22.5.
AB  - Organic light-emitting diodes (OLEDs) based on red and green phosphorescent
      iridium complexes are successfully commercialized in displays and solid-state
      lighting. However, blue ones still remain a challenge on account of their
      relatively dissatisfactory Commission International de L'Eclairage (CIE)
      coordinates and low efficiency. After analyzing the reported blue iridium
      complexes in the literature, a new deep-blue-emitting iridium complex with
      improved photoluminescence quantum yield is designed and synthesized. By rational
      screening host materials showing high triplet energy level in neat film as well
      as the OLED architecture to balance electron and hole recombination, highly
      efficient deep-blue-emission OLEDs with a CIE at (0.15, 0.11) and maximum
      external quantum efficiency (EQE) up to 22.5% are demonstrated. Based on the
      transition dipole moment vector measurement with a variable-angle spectroscopic
      ellipsometry method, the ultrahigh EQE is assigned to a preferred horizontal
      dipole orientation of the iridium complex in doped film, which is beneficial for
      light extraction from the OLEDs.

PMID- 29380905
TI  - Insights on the effectiveness of reward schemes from 10-year longitudinal case
      studies in 2 Italian regions.
AB  - BACKGROUND: Pay for performance (P4P) programs have been widely analysed in
      literature, and the results regarding their impact on performance are mixed.
      Moreover, in the real-life setting, reward schemes are designed combining
      multiple elements altogether, yet, it is not clear what happens when they are
      applied using different combinations. OBJECTIVES: To provide insights on how P4P
      programs are influenced by 5 key elements: whom, what, how, how many targets, and
      how much to reward. METHODS: A qualitative longitudinal analysis of 10 years of
      P4P reward schemes adopted by the regional administrations of Tuscany and
      Lombardy (Italy) was conducted. The effects of the P4P features on performance
      are discussed considering both overall and specific indicators. RESULTS: Both
      regions applied financial reward schemes for General Managers by linking the
      variable pay to performance. While Tuscany maintained a relatively stable
      financial incentive design and governance tools, Lombardy changed some elements
      of the design and introduced, in 2012, a P4P program aimed to reward the
      providers. The main differences between the 2 cases regard the number of targets
      (how many), the type (what), and the method applied to set targets (how).
      CONCLUSION: Considering the overall performance obtained by the 2 regions, it
      seems that whom, how, and how much to reward are not relevant in the success of
      P4P programs; instead, the number (how many) and the type (what) of targets set
      may influence the performance improvement processes driven by financial reward
      schemes.

PMID- 29380906
TI  - Osteoporotic alterations in a group of different ethnicity Brazilian
      postmenopausal women: An observational study.
AB  - OBJECTIVES: To compare peripheral bone mineral density alterations among
      Brazilian postmenopausal women from three ethnic groups considering age and body
      mass index influence; to correlate their bone mineral density with the mandibular
      cortical index (MCI); and to evaluate the influence of age, body mass index and
      ethnicity in the MCI using risk factor analysis. BACKGROUND: Osteoporosis risk is
      known to have ethical influences. However, little is known about the differences
      in ethnicity in radiomorphometric indices. MATERIALS AND METHODS: A total of 150
      postmenopausal women with different ethnicities (Caucasian, Asian and Afro
      descendant) who underwent peripheral dual X-ray absorptiometry and panoramic
      examination were included. Bone mineral density and MCI were assessed. Adjusted
      odds ratio analyses were performed on bone density and MCI considering the effect
      of age, ethnicity and body mass index. The correlations between the MCI and the
      dual X-ray absorptiometry results were made. RESULTS: Old age, low body mass
      index and non-Afro-descendant were associated with low bone density. Compared
      with Afro-descendants, Asians and Caucasians have higher chances of having
      decreased bone mass. For the MCI, statistical analysis showed that age is the
      only variable associated with osteoporotic alterations in the mandible.
      Furthermore, an inverse correlation was found between the MCI and the T-scores.
      CONCLUSION: Bone density is higher in Brazilian Afro-descendant women than in
      Caucasians and Asians. Patient's age is associated with bone density and the MCI.
      The mandibular cortical index is inversely correlated with the peripheral
      densitometry results within the study ethnic population.

PMID- 29380907
TI  - Dopamine reuptake transporter-single-photon emission computed tomography and
      transcranial sonography as imaging markers of prediagnostic Parkinson's disease.
AB  - OBJECTIVE: The objective of this study was to examine whether prediagnostic
      features of Parkinson's disease (PD) were associated with changes in dopamine
      reuptake transporter-single-photon emission computed tomography and transcranial
      sonography. METHODS: Prediagnostic features of PD (risk estimates, University of
      Pennsylvania Smell Identification Test, Rapid Eye Movement Sleep Behavior
      Disorder Screening Questionnaire, and finger-tapping scores) were assessed in a
      large cohort of older U.K. residents. A total of 46 participants were included in
      analyses of prediagnostic features and MDS-UPDRS scores with the striatal binding
      ratio on dopamine reuptake transporter-single-photon emission computed tomography
      and nigral hyperechogenicity on transcranial sonography. RESULTS: The striatal
      binding ratio was associated with PD risk estimates (P = .040), University of
      Pennsylvania Smell Identification Test (P = .002), Rapid Eye Movement Sleep
      Behavior Disorder Screening Questionnaire scores (P = .024), tapping speed (P =
      .024), and MDS-UPDRS motor scores (P = .009). Remotely collected assessments
      explained 26% of variation in the striatal binding ratio. The inclusion of MDS
      UPDRS motor scores did not explain additional variance. The size of the nigral
      echogenic area on transcranial sonography was associated with risk estimates (P <
      .001) and MDS-UPDRS scores (P = .03) only. CONCLUSIONS: The dopamine reuptake
      transporter-single-photon emission computed tomography results correlated with
      motor and nonmotor features of prediagnostic PD, supporting its potential use as
      a marker in the prodromal phase of PD. Transcranial sonography results also
      correlated with risk scores and motor signs. (c) 2018 The Authors. Movement
      Disorders published by Wiley Periodicals, Inc. on behalf of International
      Parkinson and Movement Disorder Society.

PMID- 29380908
TI  - Type-specific persistence and clearance rates of HPV genotypes in the oral and
      oropharyngeal mucosa in an HIV/AIDS cohort.
AB  - BACKGROUND: Oral high-risk human papillomavirus (HR-HPV) infections are frequent
      and persistent among the HIV-positive population and are associated with an
      increased risk for head and neck cancer (HNC). In this study, we sought to
      determine the incidence, persistence and clearance of HPV infections in oral and
      oropharyngeal samples from HIV/AIDS subjects. METHODS: A longitudinal,
      observational and analytical study was performed with an ongoing cohort of
      HIV/AIDS subjects in Mexico City (September 2013-February 2015). The study was
      approved by institutional committees, and demographic and clinical data were
      registered. At the baseline and three-month visits, oral examinations and
      cytobrush samples were obtained. DNA was purified, quantified and used to detect
      an HPV-L1 gene fragment by nested PCR, using MY09/MY11 and GP5 + /GP6 + primers.
      HPV DNA products were purified, sequenced and typed according to HPV databases.
      Risk factors were assessed, and a multivariate modelling approach was used to
      determine independent effects. RESULTS: This study included 97 HIV/AIDS
      individuals (91% men [86.4% of which are men who have sex with men], median age:
      36 years, 72.2% under HAART). From the baseline visit, HPV was observed in 55.7%
      (HR-HPV: 26.8%; HPV-18: 24.1%), with a higher HPV-positive samples for smokers
      (61.1 vs 32.6%, P = .005). The three-month overall HPV incidence was 33.9%; type
      specific HPV persistence was 33.3% (HR-HPV: 13.3%); and 13 of the 33 (39.4%)
      baseline HPV-positive individuals cleared the infection (HR-HPV: 53.8%).
      CONCLUSIONS: Although HR-HPV persistence was low, and clearance of the infection
      was observed in most cases, a close follow-up is necessary, given the increase in
      HNC among HIV-subjects, particularly HPV-related cancer.

PMID- 29380909
TI  - The function of patient-centered care in mitigating the effect of nursing
      shortage on the outcomes of care.
AB  - BACKGROUND: The shortage of nursing staff is a national and international issue.
      Inadequate number of hospital nurse staff leads to poor health care services. Yet
      the effects of patient-centeredness between the relationships of nursing shortage
      on the quality of care (QC) and patient safety (PS) have not been explored. The
      aim of this study was to examine the mediating effects of patient-centeredness on
      the relationship of nursing shortage on the QC and PS in the Medical and Surgical
      Wards, in Malaysian private hospitals. METHOD: A descriptive, cross-sectional
      study was carried out on 12 private hospitals. Data was gathered, through a self-
      administered questionnaire, from 652 nurses, with a 61.8% response rate.
      Stratified simple random sampling was used to allow all nurses to participate in
      the study. Hayes PROCESS macro-regression analyses were conducted to explore the
      mediating effects of patient-centeredness on the relationships of hospital nurse
      staffing on the QC and PS. RESULTS: Patient-centeredness mediated the
      relationships of hospital nurse staffing on both the QC (F = 52.73 and P = 0.000)
      and PS (F = 31.56 and P = 0.000). CONCLUSION: Patient-centeredness helps to
      mitigate the negative associations of nursing shortage on the outcomes of care.
      The study provides a guide for hospital managers, leaders, decision-makers, risk
      managers, and policymakers to maintain adequate staffing level and instill the
      culture of patient-centeredness in order to deliver high quality and safer care.

PMID- 29380911
TI  - Upregulation of Klotho potentially inhibits pulmonary vascular remodeling by
      blocking the activation of the Wnt signaling pathway in rats with PM2.5-induced
      pulmonary arterial hypertension.
AB  - We evaluated the effects of Klotho on pulmonary vascular remodeling and cell
      proliferation and apoptosis in rat models with PM2.5-induced pulmonary arterial
      hypertension (PAH) via the Wnt signaling pathway. After establishing rat models
      of PM2.5-induced PAH, these Sprague-Dawley male rats were randomized into control
      and model groups. Cells extracted from the model rats were sub-categorized into
      different groups. Activation of Wnt/beta-catenin signaling transcription factor
      was detected by a TOPFlash/FOPFlash assay. A serial of experiment was conducted
      to identify the mechanism of Klotho on PHA via the Wnt signaling pathway. VEGF
      levels and PaCO2 content were higher in the model group, while PaO2, NO2- /NO3-
      content and Klotho level was lower compared to the control group. In comparison
      to the control group, the model group had decreased Klotho and Bax levels, and
      elevated Wnt-1, beta-catenin, bcl-2, survivin, and PCNA expression, VEGF, IL-6,
      TNF-alpha, TNF-beta1, and bFGF levels, as well as the percentage of pulmonary
      artery ring contraction. The Klotho vector, DKK-1 and DKK-1 + Klotho vector
      groups exhibited reduced cell proliferation, luciferase activity, and the
      expression of Wnt-1, beta-catenin, bcl-2, survivin, and PCNA, as well as
      shortened S phase compared with the blank and NC groups. Compared with the Klotho
      vector and DKK-1 groups, the DKK-1 + Klotho vector groups had reduced cell
      proliferation, luciferase activity, and the expression of Wnt-1, beta-catenin,
      bcl-2, survivin, and PCNA, as well as a shortened S phase. Conclusively, Klotho
      inhibits pulmonary vascular remodeling by inactivation of Wnt signaling pathway.

PMID- 29380910
TI  - Chemical and thyroid hormone profile of the bone marrow interstitial fluid in
      hematologic disorders and patients without primary hematologic disorders.
AB  - Bone marrow interstitial fluid (BMIF) has not been well characterized. BMIF was
      isolated from 60 patients including plasma cell dyscrasias (PCD, n = 33), other
      primary hematologic disorders (OHD, n = 15), and patients with secondary or
      nonhemtologic disorders (NHD, n = 12) and analyzed for an array of chemical
      constituents. These included total cholesterol, glucose, phosphate, creatinine,
      urea, total protein, albumin, globulins, total bilirubin, aspartate
      aminotransferase, lactate dehydrogenase, sodium, osmolarity, free
      triiodothyronine (free T3), total triiodothyronine (total T3), and free
      tetraiodothyronine (free T4). Levels of BMIF components were compared between
      patient groups and to plasma levels. Compared with plasma, total cholesterol,
      total protein, total bilirubin, sodium, and calculated osmolarity were lower in
      BMIF in all groups (P < 0.05). Calculated globulins and aspartate
      aminotransferase were lower in BMIF of PCD patients and patients with NHD.
      Albumin was lower in BMIF of patients with PCD and patients with OHD. Lastly,
      free T4 was significantly higher in BMIF of patients with PCD and patients with
      OHD. Similar results were demonstrated in a separate analysis performed in
      patients with multiple myeloma. To conclude, the chemical and thyroid hormone
      composition of BMIF differs significantly from plasma in several key
      constituents.

PMID- 29380912
TI  - Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity,
      injury severity, and neurometabolism.
AB  - Following traumatic brain injury (TBI), there is significant secondary damage to
      cerebral tissue from increased free radicals and impaired mitochondrial function.
      This imbalance between reactive oxygen species (ROS) production and the
      effectiveness of cellular antioxidant defenses is termed oxidative stress. Often
      there are insufficient antioxidants to scavenge ROS, leading to alterations in
      cerebral structure and function. Attenuating oxidative stress following a TBI by
      administering an antioxidant may decrease secondary brain injury, and currently
      many drugs and supplements are being investigated. We explored an over-the
      counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent
      antioxidant naturally produced in brain mitochondria. We administered intra
      arterial ubiquinol to rats to determine if it would reduce mitochondrial damage,
      apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly
      assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before
      TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found
      when ubiquinol was administered before or after TBI, rats had an acute reduction
      in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI
      severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal
      hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton
      magnetic resonance spectroscopy did not show attenuated injury-induced changes.
      These findings are the first to show that ubiquinol preserves mitochondria and
      reduces cellular injury severity after TBI, and support further study of
      ubiquinol as a promising adjunct therapy for TBI.

PMID- 29380913
TI  - Review: Vascular dementia: clinicopathologic and genetic considerations.
AB  - The incidence and severity of cerebrovascular disease (CVD) increase with
      advancing age, as does the risk of developing Alzheimer's disease (AD). Not
      surprisingly, heterogeneous forms of CVD may coexist with AD changes in the
      'ageing brain'. These include angiopathies (affecting both large and small
      arteries) that result from 'classical' risk factors (hypertension, smoking and
      diabetes) and others (cerebral amyloid angiopathy) that are biochemically closely
      linked to AD. The morphologic consequences of these various vascular diseases are
      infarcts and/or haemorrhages of varying sizes within the brain, which lead to
      neurocognitive decline that may mimic AD - though the vascular abnormalities are
      usually detectable by neuroimaging. More subtle effects of CVD may include
      neuroinflammation and biochemical 'lesions' that have no reliable morphologic
      correlate and thus escape the attention of even an experienced Neuropathologist.
      The pathogenesis of hippocampal injury resembling ischaemic change - commonly
      seen in the brains of geriatric subjects - remains controversial. In recent
      years, genetically determined forms of microangiopathy (e.g. CADASIL, CARASIL,
      Trex1-related microangiopathies, CARASAL, familial forms of cerebral amyloid
      angiopathy or CAA) have provided interesting cellular and molecular clues to the
      pathogenesis of sporadic microvascular disease such as arteriolosclerosis and AD
      related CAA.

PMID- 29380914
TI  - Assessing managerial information needs: Modification and evaluation of the
      Hospital Shift Leaders' Information Needs Questionnaire.
AB  - AIMS: The aims were (1) to evaluate the modified version of the Intensive Care
      Unit Information Need Questionnaire for the broader hospital setting, and (2) to
      describe the differences in respondents' managerial activities and information
      needs according to the position held by the respondent and the type of hospital
      unit. BACKGROUND: Information systems do not support managerial decision-making
      sufficiently and information needed in the day-to-day operations management in
      hospital units is unknown. METHODS: An existing questionnaire was modified and
      evaluated. Shift leaders, that is, the nurses and physicians responsible for the
      day-to-day operations management in hospital units were reached using purposive
      sampling (n = 258). RESULTS: The questionnaire ascertained the importance of
      information. Cronbach's alpha ranged from .85-.96 for the subscales. Item - total
      correlations showed good explanatory power. Managerial activities and information
      needs differed between respondents in different positions, although all shared
      about one-third of important information needs. The response rate was 26% (n =
      67). CONCLUSIONS: The validity and reliability of the questionnaire were good.
      Attention should be paid to the positions of shift leaders when developing
      information systems. IMPLICATIONS FOR NURSING MANAGEMENT: The questionnaire can
      be used to determine important information when developing information systems to
      support day-to-day operations management in hospitals.

PMID- 29380915
TI  - Carbon and nitrogen stable isotopes in U.S. milk: Insight into production
      process.
AB  - RATIONALE: Stable isotope analysis (SIA), a potential method of verifying the
      geographic origin and production method of dairy products, has not been applied
      to United States (U.S.) dairy samples on a national scale. To determine the
      potential of carbon and nitrogen SIA in authenticity assessment of U.S. dairy
      products, we analyzed a geographically representative collection of conventional
      milk samples to determine isotopic variations with (1) Purchase Location and (2)
      Macronutrient Content. METHODS: A total of 136 milk samples spanning five
      commercially available varieties (3.25% [i.e., 'whole'], 2%, 1%, 0% [i.e.,
      'skim'] and 1% chocolate) were collected from randomly selected counties across
      the U.S. as part of the United States Department of Agriculture's (USDA's)
      National Food and Nutrient Analysis program. delta13 C and delta15 N values of
      bulk samples determined via elemental analysis/isotope ratio mass spectrometry
      (EA/IRMS) were used to assess the contribution of fat content, added sugar
      content and census-designated region of collection to isotopic variations within
      the dataset. RESULTS: There was a negative linear relationship between fat
      content and delta13 C values, with average milk delta13 C values decreasing by
      0.330/00 for each 8.75% increase in dry weight (1% wet weight) fat content. The
      average delta13 C value of flavored 1% chocolate milk samples, which contain an
      additional 12 g of added sugar, was 2.050/00 higher than that of 1% unflavored
      milk (-16.470/00 for chocolate milk vs -18.520/00 for unflavored milk). When
      controlling for macronutrient content, milk samples collected in West region
      supermarkets possessed significantly lower delta13 C values than samples
      collected from Midwest, South, and Northeast regions. delta15 N values did not
      vary with macronutrient content or region of collection. CONCLUSIONS: Carbon
      stable isotope ratios in U.S. milk samples varied with macronutrient content and
      region of purchase, suggesting that SIA can provide insight into production
      processes within the U.S. dairy industry, with potential applications in national
      food adulteration and authentication efforts.

PMID- 29380916
TI  - Online information for parents caring for their premature baby at home: A focus
      group study and systematic web search.
AB  - BACKGROUND: Online resources are a source of information for parents of premature
      babies when their baby is discharged from hospital. OBJECTIVES: To explore what
      topics parents deemed important after returning home from hospital with their
      premature baby and to evaluate the quality of existing websites that provide
      information for parents post-discharge. METHODS: In stage 1, 23 parents living in
      Northern Ireland participated in three focus groups and shared their information
      and support needs following the discharge of their infant(s). In stage 2, a World
      Wide Web (WWW) search was conducted using Google, Yahoo and Bing search engines.
      Websites meeting pre-specified inclusion criteria were reviewed using two website
      assessment tools and by calculating a readability score. Website content was
      compared to the topics identified by parents in the focus groups. RESULTS: Five
      overarching topics were identified across the three focus groups: life at home
      after neonatal care, taking care of our family, taking care of our premature
      baby, baby's growth and development and help with getting support and advice.
      Twenty-nine sites were identified that met the systematic web search inclusion
      criteria. Fifteen (52%) covered all five topics identified by parents to some
      extent and 9 (31%) provided current, accurate and relevant information based on
      the assessment criteria. CONCLUSION: Parents reported the need for information
      and support post-discharge from hospital. This was not always available to them,
      and relevant online resources were of varying quality. Listening to parents needs
      and preferences can facilitate the development of high-quality, evidence-based,
      parent-centred resources.

PMID- 29380917
TI  - Can I relate? A review and guide for nurse managers in leading generations.
AB  - AIMS: The purpose of this review is to help the nurse leader develop an
      understanding of the five generations currently in the health care workforce by
      providing defining characteristics, general behaviours, and strategies for the
      nurse manager to employ for each generational cohort. BACKGROUND: Generations are
      groups of people born during the same 15-20 year time period who share similar
      experiences before adulthood, which shape long-term behaviours. Key descriptors
      and characteristics are provided. EVALUATION: The current generational cohorts in
      the health care workforce are Traditionalists (born between 1922 and 1945), baby
      boomers (born between 1946 and 1964), Generation X (born between 1965 and 1979),
      millennials (born between 1980 and 1995), and Generation Z (born after 1995). KEY
      ISSUES: Health care teams often comprise members of three or more generations.
      Intergenerational differences in team members can result in challenges; however,
      different perspectives provided by multiple generations can be used
      advantageously to strengthen the team's efficiency and outcomes. CONCLUSIONS:
      There are strengths in each generation. Key differences can be harnessed to build
      stronger teams through comprehensive communication strategies, customized reward
      systems, and workplace flexibility. Examples are provided for each area.
      IMPLICATIONS: Managers can use intergenerational differences to create a rich
      environment that bridges generational differences and fosters workforce cohesion.

PMID- 29380919
TI  - Symptomatic arrhythmia in the form of multiple premature ventricular
      extrasystoles as the first symptom of polymyositis.
AB  - Polymyositis (PM) is an autoimmune disease characterized by the involvement of
      multiple internal organs, including the cardiovascular system. The involvement of
      heart is observed in up to 75% of patients with PM. Conduction and rhythm
      disorders are one of the most common cardiological abnormalities in these
      patients. The presented clinical case is the patient where ventricular arrhythmia
      (in the form of multiple premature ventricular extrasystoles) was the first
      symptom of polymyositis.

PMID- 29380918
TI  - ASPRE trial: incidence of preterm pre-eclampsia in patients fulfilling ACOG and
      NICE criteria according to risk by FMF algorithm.
AB  - OBJECTIVE: To report the incidence of preterm pre-eclampsia (PE) in women who are
      screen positive according to the criteria of the National Institute for Health
      and Care Excellence (NICE) and the American College of Obstetricians and
      Gynecologists (ACOG), and compare the incidence with that in those who are screen
      positive or screen negative by The Fetal Medicine Foundation (FMF) algorithm.
      METHODS: This was a secondary analysis of data from the ASPRE study. The study
      population consisted of women with singleton pregnancy who underwent prospective
      screening for preterm PE by means of the FMF algorithm, which combines maternal
      factors and biomarkers at 11-13 weeks' gestation. The incidence of preterm PE in
      women fulfilling the NICE and ACOG criteria was estimated; in these patients the
      incidence of preterm PE was then calculated in those who were screen negative
      relative to those who were screen positive by the FMF algorithm. RESULTS: A total
      of 34 573 women with singleton pregnancy delivering at >= 24 weeks' gestation
      underwent prospective screening for preterm PE, of which 239 (0.7%) cases
      developed preterm PE. At least one of the ACOG criteria was fulfilled in 22 287
      (64.5%) pregnancies and the incidence of preterm PE was 0.97% (95% CI, 0.85
      1.11%); in the subgroup that was screen positive by the FMF algorithm the
      incidence of preterm PE was 4.80% (95% CI, 4.14-5.55%), and in those that were
      screen negative it was 0.25% (95% CI, 0.18-0.33%), with a relative incidence in
      FMF screen negative to FMF screen positive of 0.051 (95% CI, 0.037-0.071). In
      1392 (4.0%) pregnancies, at least one of the NICE high-risk criteria was
      fulfilled, and in this group the incidence of preterm PE was 5.17% (95% CI, 4.13
      6.46%); in the subgroups of screen positive and screen negative by the FMF
      algorithm, the incidence of preterm PE was 8.71% (95% CI, 6.93-10.89%) and 0.65%
      (95% CI, 0.25-1.67%), respectively, and the relative incidence was 0.075 (95% CI,
      0.028-0.205). In 2360 (6.8%) pregnancies fulfilling at least two of the NICE
      moderate-risk criteria, the incidence of preterm PE was 1.74% (95% CI, 1.28
      2.35%); in the subgroups of screen positive and screen negative by the FMF
      algorithm the incidence was 4.91% (95% CI, 3.54-6.79%) and 0.42% (95% CI, 0.20
      0.86%), respectively, and the relative incidence was 0.085 (95% CI, 0.038-0.192).
      CONCLUSION: In women who are screen positive for preterm PE by the ACOG or NICE
      criteria but screen negative by the FMF algorithm, the risk of preterm PE is
      reduced to within or below background levels. The results provide further
      evidence to support the personalized risk-based screening method that combines
      maternal factors and biomarkers. Copyright (c) 2018 ISUOG. Published by John
      Wiley & Sons Ltd.

PMID- 29380920
TI  - Interleukin-10 -1082A/G polymorphism is associated with renal parenchymal damage
      in congenital anomalies of the kidney and urinary tract.
AB  - AIM: The aim of the study was to investigate whether the functional IL10-1082A/G
      polymorphism exert a role in congenital anomalies of the kidney and urinary tract
      (CAKUT) in children. Also, the serum IL-10 and its association with genotype and
      renal parenchymal damage in CAKUT were explored. METHODS: In current case-control
      study, 134 paediatric cases of CAKUT and 382 unrelated controls were included.
      The genotyping of IL10-1082A/G polymorphism was performed by amplification
      refractory mutation system-PCR and IL-10 serum level was determined by ELISA.
      RESULTS: Although, the genotype and allelic frequencies of IL10-1082 A/G
      polymorphism in cases and controls were similar (chi2=0.459; p=0.79 and
      chi2=0.426; p=0.51, respectively), significant different genotype distribution
      between patients with or without parenchymal damage/reduction was observed
      (chi2=6.9; p=0.032). The GG-genotype was more frequent in cases with renal
      parenchymal damage/reduction compared to patients with preserved parenchyma (22%
      vs. 9%; OR=2.987; 95% CI:0.979-9.468; p=0.031). Contrary, the heterozygous
      genotype was less frequent among cases with parenchymal damage/reduction compared
      to cases with preserved parenchyma (39% vs. 59%; OR=0.453; 95% CI:0.214-0.958;
      p=0.024). Additionally, the serum IL-10 was significantly higher in CAKUT
      patients compared to age-sex-matched controls (median 11.98; IQR:7.14-31.6 vs.
      5.92; IQR:4.68-14.8; p=0.0057). Among carriers of GG-genotype significantly
      higher IL-10 level was detected in cases with parenchymal damage/reduction, than
      cases with preserved parenchyma (p=0.028). CONCLUSION: Our results suggested that
      the functional -1082A/G polymorphism in IL10 is associated with risk of renal
      parenchymal damage/reduction rather than genetic predisposition to CAKUT.
      Additionally, our study supposes that immunoregulatory cytokine IL-10 might has
      significant role in CAKUT.

PMID- 29380921
TI  - Correlation between computer tomography-derived scar topography and critical
      ablation sites in postinfarction ventricular tachycardia.
AB  - BACKGROUND: Myocardial wall thickness (WT) in patients with a prior myocardial
      infarction has been used to indicate scarring. However, the correlation of WT
      with sites critical to ventricular tachycardia (VT) has not been previously
      investigated. The purpose of this study was to correlate electroanatomic mapping
      data obtained during VT ablation with WT determined by cardiac computed
      tomography (CT). METHODS AND RESULTS: Cardiac CTs were performed in 15
      consecutive patients (mean age 63 +/- 10 years, 86% male, left ventricular
      ejection fraction 27 +/- 12%) with a prior infarct referred for VT ablation. The
      CTs were registered to the electroanatomic maps obtained during the mapping
      procedure. Pacing was performed throughout the scar at sites with fractionated
      electrograms and isolated potentials. Ablation sites were identified by pace
      mapping or entrainment-mapping and these sites were correlated with WT. Bipolar
      and unipolar voltage amplitude and bipolar electrogram width correlated with WT
      (correlation coefficient: 0.63, 0.65, and 0.41, respectively, P < 0.001).
      Ablation target sites were identified for 58 of 113 inducible VTs. The ablation
      target sites were located on CT-defined ridges (WT: 4.2 +/- 1.2 mm) bordered by
      areas of thinning (WT: 2.6 +/- 1.1 mm, P < 0.0001) in 14 of 15 patients. Ablation
      targets were found on ridges in 49 of 58 VTs (84%) for which target sites were
      identified. A total of 70 ridges were localized in the 15 patients. VT became
      noninducible postablation in 11 of 15 patients (73%). CONCLUSION: WT measured by
      CT identifies ridges of myocardial tissue that often are critical for
      postinfarction VT and that can be appropriate target sites for ablation.

PMID- 29380922
TI  - Longitudinal changes in vascular function parameters in pregnant women with
      chronic hypertension and association with adverse outcome: a cohort study.
AB  - OBJECTIVES: Raised vascular function measures are associated with development of
      adverse maternal and perinatal outcomes in low risk pregnancy. This study aimed
      to evaluate the association between longitudinal vascular function parameters and
      adverse outcomes in pregnant women with chronic hypertension. METHODS: Pregnant
      women recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs
      lAbetalol as antihypertensive treatment) trial in three UK maternity units had
      serial pulse wave analyses performed using the Arteriograph(r) (Tensiomed,
      Budapest, Hungary) while in a sitting position from 12 weeks onwards. Statistical
      analysis used random-effects logistic regression models and compared those who
      developed superimposed pre-eclampsia (SPE) to those who did not, women who
      delivered a small for gestational age infant (<10th birthweight centile) (SGA10)
      to those who delivered an infant with birthweight >10th centile, and women of
      Black ethnicity with women of non-Black ethnicity. RESULTS: The cohort included
      97 women (90% (n=87) randomised to antihypertensive treatment), with up to six
      longitudinal vascular function assessments (mean 3), (57% (n=55) of Black
      ethnicity) with chronic hypertension and singleton pregnancies. SPE was diagnosed
      in 18% (n=17) and 30% (n=29) of infants were SGA10. In women who developed
      subsequent SPE compared to those who did not, mean brachial systolic blood
      pressure (SBP) (148 vs 139 mmHg; p=0.002), mean diastolic blood pressure (DBP)
      (87 vs 82 mmHg; p=0.01), mean central aortic pressure (139 vs 128 mmHg; p=0.001)
      and mean augmentation index (AIX-75) (29 vs 22%; p=0.01) were significantly
      higher across gestation. Mean brachial SBP (146 vs 138 mmHg; p=0.001), mean DBP
      (86 vs 82 mmHg; p=0.01), mean central aortic pressure (137 vs 127 mmHg;
      p=<0.0001), and mean PWV (9.1 vs 8.5 m/s; p=0.02) were higher across gestation in
      women who delivered an SGA10 infant compared to women who delivered an infant
      with birthweight >10th centile. No longitudinal differences were found in the
      vascular function parameters in women of Black ethnicity compared to non-Black
      ethnicity. CONCLUSION: There are persistent differences in vascular function
      parameters and brachial blood pressure through pregnancy in women with chronic
      hypertension who later develop adverse maternal and perinatal outcome. Further
      investigation of the possible clinical use of these findings is warranted.

PMID- 29380923
TI  - Phacoemulsification outcomes in Boston terriers as compared to non-Boston
      terriers: a retrospective study (2002-2015).
AB  - OBJECTIVES: To compare visual outcome and cause of blindness between two groups
      of dogs undergoing phacoemulsification. ANIMALS STUDIED: Study population
      consisted of 35 Boston terriers (BT; 70 eyes) and 77 non-Boston terriers (NBT;
      154 eyes) that underwent bilateral phacoemulsification surgery. PROCEDURES:
      Medical records were reviewed to determine visual outcome, complications leading
      to blindness and follow-up. A Kaplan-Meier survival curve was used to estimate
      surgical success at 1 and 2 years postoperatively. RESULTS: Eleven of 35 BT
      developed known vision loss, with 12 of 70 (17.1%) eyes becoming blind within one
      year of surgery, and 17 of 77 NBT developed known vision loss, with 19 of 154
      (12.3%) eyes becoming blind within 1 year of surgery. No further vision loss was
      reported among those BT with a 2-year follow-up. In the NBT group, seven
      additional dogs, a total of 24 of 77 NBT developed vision loss, with a known
      total of 31 of 154 (20.1%) eyes becoming blind within two years of surgery. These
      results were not significantly different. The overall surgical success in both
      groups based on individual eyes was estimated to be between 80 and 90% at 1 year
      postsurgery and between 65 and 80% at 2 years postsurgery. Glaucoma was the
      leading cause of vision loss in both groups. CONCLUSIONS: There was no
      significant difference in visual outcomes between a group of BT and a group of
      NBT undergoing bilateral phacoemulsification at the University of Tennessee
      between 2002 and 2015. Glaucoma was the leading cause of vision loss in both
      groups.

PMID- 29380924
TI  - Network geometry of evidence from randomised controlled trials addressing donor
      selection and source of haematopoietic progenitor cells used in allogeneic
      transplantation: a systematic scoping review.
AB  - BACKGROUND AND METHODS: A scoping review of randomised controlled trials (RCTs)
      addressing source of cells and choice of donor for allogeneic haematopoietic cell
      transplantation (HCT) was performed to create a network of best evidence that
      allows us to identify new potential indirect comparisons for the strategic
      development of future studies that connect to the existing evidence network.
      RESULTS: A total of 19 eligible RCTs (2589 total patients) were identified. Nine
      studies (1566 patients) compared clinical outcomes following the use of
      peripheral blood progenitor cells (PBPCs) with bone marrow (BM) from matched
      related donors (eight studies) or matched unrelated donors (one study). The
      remaining studies compared BM or PBPCs with various methods of BM stimulation or
      manipulation (six studies), compared different methods of surface molecule-based
      selection and/or depletion of grafts (two studies) or compared the optimal number
      of units for paediatric cord blood transplantation (two studies). No published
      RCTs compared different types of donors. The geometry of the evidence network was
      analysed to identify opportunities for potential novel indirect comparisons and
      to identify opportunities to expand the network. Few indirect comparisons are
      currently feasible due to small sample size and heterogeneity in patient
      diagnoses and demographics between treatment nodes in the network. CONCLUSION:
      More RCTs that enrol greater numbers of similar patients are needed to leverage
      the current evidence network concerning donor choice and source of cells used in
      allogeneic HCT.

PMID- 29380925
TI  - Changes in ductus venosus velocity ratios after fetoscopic laser surgery for twin
      twin transfusion syndrome.

PMID- 29380926
TI  - Integration of paper spray ionization high-field asymmetric waveform ion mobility
      spectrometry for forensic applications.
AB  - RATIONALE: Paper spray ionization (PSI) is an attractive ambient ionization
      source for mass spectrometry (MS) since it allows the combination of surface
      sampling and ionization. The minimal sample preparation inherent in this approach
      greatly reduces the time needed for analysis. However, the ions generated from
      interfering compounds in the sample and the paper substrate may interfere with
      the analyte ions. Therefore, the integration of PSI with high-field asymmetric
      ion mobility spectrometry (FAIMS) is of significant interest since it should
      reduce the background ions entering the mass analyzer without complicating the
      analysis or increasing analysis time. Here we demonstrate the integration of PSI
      with FAIMS/MS and its potential for analysis of samples of forensic interest.
      METHODS: In this work, the parameters that can influence the integration,
      including sampling and ionization by paper spray, the FAIMS separation of
      analytes from each other and background interferences, and the length of time
      that a usable signal can be observed for explosives on paper, were evaluated with
      the integrated system. RESULTS: In the negative ion analysis of 2,4,6
      trinitrotoluene (TNT), pentaerythritol tetranitrate (PETN), octahydro-1,3,5,7
      tetranitro-1,3,5,7-tetrazocine (HMX), and 1,3,5-trinitroperhydro-1,3,5-triazine
      (RDX), amounts as low as 1 ng on paper were readily observed. The successful
      positive ion separation of a set of illicit drugs including heroin,
      methamphetamine, and cocaine was also achieved. In addition, the positive ion
      analysis of the chemical warfare agent simulants dimethyl methylphosphonate
      (DMMP) and diisopropyl methylphosphonate (DIMP) was evaluated. CONCLUSIONS: The
      integration of PSI-FAIMS/MS was demonstrated for the analyses of explosives in
      negative ion mode and for illicit drugs and CW simulants in positive mode. Paper
      background ions that could interfere with these analyses were separated by FAIMS.
      The compensation voltage of an ion obtained by FAIMS provided an additional
      identification parameter to be combined with the mass spectrum for each analyte.

PMID- 29380928
TI  - Type D personality is associated with increased desire for alcohol in response to
      acute stress.
AB  - Type D personality (the combination of negative affectivity and social
      inhibition) is associated with high levels of alcohol consumption. We examined if
      Type D was associated with higher levels of alcohol use, and if Type D was
      associated with desire for alcohol in response to a social stressor. In an
      experimental study, participants (n = 138) completed measures of Type D, stress,
      and alcohol use. They also took part in a stress-inducing public speaking task
      and provided measures of desire for alcohol at baseline, stressor, and recovery.
      Type D was associated with higher levels of alcohol use, stress, and desire for
      alcohol at stressor and recovery. Mixed measures analysis of variance
      demonstrated that there was a significant group effect of Type D (F(1, 136) =
      6.86, p < .05) and a significant time * Type D interaction (F(1.50, 204.49) =
      3.44, p < .05) on desire for alcohol. Type D individuals exhibited significantly
      higher levels of desire for alcohol during the stressor and recovery phases,
      compared to non-Type D individuals suggesting that Type D individuals may be
      motivated to consume alcohol in order to cope with stressful situations.

PMID- 29380927
TI  - Increased hyperpolarized [1-13 C] lactate production in a model of joint
      inflammation is not accompanied by tissue acidosis as assessed using
      hyperpolarized 13 C-labelled bicarbonate.
AB  - Arthritic conditions are a major source of chronic pain. Furthering our
      understanding of disease mechanisms creates the opportunity to develop more
      targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human
      synovial fluid suggest that acidosis occurs, but that this is highly variable
      between individuals. Here we sought to determine if tissue acidosis occurs in a
      widely used rodent arthritis model: complete Freund's adjuvant (CFA)-induced
      inflammation. CFA robustly evoked paw and ankle swelling, concomitant with
      worsening clinical scores over time. We used magnetic resonance spectroscopic
      imaging of hyperpolarized [1-13 C]pyruvate metabolism to demonstrate that CFA
      induces an increase in the lactate-to-pyruvate ratio. This increase is indicative
      of enhanced glycolysis and an increased lactate concentration, as has been
      observed in the synovial fluid from RA patients, and which was correlated with
      acidosis. We also measured the 13 CO2 /H13 CO3- ratio, in animals injected with
      hyperpolarized H13 CO3- , to estimate extracellular tissue pH and showed that
      despite the apparent increase in glycolytic activity in CFA-induced inflammation
      there was no accompanying decrease in extracellular pH. The pH was 7.23 +/- 0.06
      in control paws and 7.32 +/- 0.09 in inflamed paws. These results could explain
      why mice lacking acid-sensing ion channel subunits 1, 2 and 3 do not display any
      changes in mechanical or thermal hyperalgesia in CFA-induced inflammation.

PMID- 29380929
TI  - Checkpoint molecule expression by B and T cell lymphomas in dogs.
AB  - Immunotherapies targeting checkpoint molecule programmed cell death 1 (PD-1)
      protein were shown to be effective for treatment of non-Hodgkin lymphoma in
      people, but little is known about the expression of PD-1 or its ligand PD-L1 by
      canine lymphoma. Therefore, flow cytometry was used to analyse expression of PD-1
      and PD-L1 in canine lymphoma, using fine-needle aspirates of lymph nodes from 34
      dogs with B cell lymphoma (BCL), 6 dogs with T cell lymphoma (TCL) and 11 dogs
      that had relapsed. Furthermore, fine-needle aspirates were obtained from 17
      healthy dogs for comparison. Lastly, the impact of chemotherapy resistance on
      expression of PD-1 and PD-L1 was assessed in vitro. These studies revealed
      increased expression of PD-L1 by malignant B cells compared to normal B cells. In
      the case of TCL, tumour cells and normal T cells both showed low to negative
      expression of PD-1 and PD-L1. In addition, tumour infiltrating lymphocytes from
      both BCL and TCL had increased expression of both PD-1 and PD-L1 expression
      compared to B and T cells from lymph nodes of healthy animals. In vitro,
      chemotherapy-resistant BCL and TCL cell lines exhibited increases in both PD-1
      and PD-L1 expression, compared to non-chemotherapy selected tumour cells. These
      findings indicate that canine lymphomas exhibit upregulated checkpoint molecule
      expression, though the impact of checkpoint molecule expression on tumour
      biological behaviour remains unclear.

PMID- 29380932
TI  - Brain atrophy in middle-aged subjects with Type 2 diabetes mellitus, with and
      without microvascular complications.
AB  - BACKGROUND: The rapid rise in Type 2 diabetes mellitus (T2DM) among young adults
      makes it important to understand structural changes in the brain at a presenile
      stage. This study examined global and regional brain atrophy in middle-aged
      adults with T2DM, with a focus on those without clinical evidence of
      microvascular complications. METHODS: The study recruited 66 dementia-free middle
      aged subjects (40 with T2DM, 26 healthy volunteers [HVs]). Patients were grouped
      according to the presence (T2DM-C; n = 20) or absence (T2DM-NC; n = 20) of
      diabetic microvascular complications. Global brain volume (including gray matter
      [GM] and white matter) was calculated based on voxel-based morphometry analysis.
      Regional GM volumes were further extracted using the anatomical automatic
      labeling template. RESULTS: There was a significant difference in global brain
      volume among groups (P = 0.003, anova). Global brain volume was lower in T2DM-C
      patients than in both T2DM-NC patients and HVs (mean [+/-SD] 0.720 +/- 0.024 vs
      0.736 +/- 0.021 and 0.743 +/- 0.019, respectively; P = 0.032 and P = 0.001,
      respectively). Regional analysis showed significant GM atrophy in the right
      Rolandic operculum (t = 3.42, P = 0.001) and right superior temporal gyrus (t =
      2.803, P = 0.007) in T2DM-NC patients compared with age- and sex-matched HVs.
      CONCLUSIONS: Brain atrophy is present in dementia-free middle-aged adults with
      T2DM. Regional brain atrophy appears to be developing even in those with no
      clinical evidence of microvascular disturbances. The brain seems to be
      particularly vulnerable to metabolic disorders prior to peripheral microvascular
      pathologies associated with other target organs.

PMID- 29380931
TI  - N-terminal pro-B-type natriuretic peptide and prognosis in Caucasian vs. Asian
      patients with heart failure.
AB  - AIMS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is the most
      frequently used biomarker in heart failure (HF), but its prognostic utility
      across ethnicities is unclear. METHODS AND RESULTS: This study included 546
      Caucasians with HF from the Coordinating Study Evaluating Outcomes of Advising
      and Counseling in Heart Failure and 578 Asians with HF from the Singapore Heart
      Failure Outcomes and Phenotypes study. NT-proBNP was measured at discharge after
      HF hospitalization. The studied outcome was a composite of all-cause mortality
      and HF hospitalization at 18 months. Compared with Caucasian patients, Asian
      patients were younger (63 +/- 12 vs. 71 +/- 11 years); less often female (26% vs.
      39%); and had lower body mass index (26 vs. 27 kg/m2 ), better renal function (61
      +/- 37 vs. 54 +/- 20 mL/min/1.73 m2 ), lower rates of atrial fibrillation (25%
      vs. 46%), strikingly higher rates of diabetes (59% vs. 30%), and higher rates of
      hypertension (76% vs. 44%). Despite these clear inter-group differences in
      individual drivers of NT-proBNP, average levels were similar in Asians [2709
      (1350, 6302) pg/mL] and Caucasians [2545 (1308, 5484) pg/mL] (P = 0.514). NT
      proBNP was strongly associated with outcome [hazard ratio 1.28 (per doubling),
      95% confidence interval 1.18-1.39, P < 0.001], regardless of ethnicity
      (Pinteraction  = 0.719). NT-proBNP was similarly associated with outcome in HF
      with reduced and preserved ejection fraction in Asian (Pinteraction  = 0.776) and
      Caucasian patients (Pinteraction  = 0.558). CONCLUSIONS: NT-proBNP has similar
      prognostic performance in Asians and Caucasians with HF despite ethnic
      differences in known clinical determinants of plasma NT-proBNP.

PMID- 29380933
TI  - Change in perceived stress and 2-year change in cognitive function among older
      adults: The Irish Longitudinal Study on Ageing.
AB  - Prolonged or severe stress can adversely affect older adults' cognitive function,
      but population-based studies investigating this relationship over time are rare.
      Previous studies have largely focused on stress either evaluated at a single time
      point or linked to specific life events. This study aimed to investigate whether
      a change in perceived stress over 2 years predicts a change in cognitive
      performance over the same time period in a population-based sample of older
      adults. Data from the first 2 waves of The Irish Longitudinal Study on Ageing
      were analyzed. Five thousand and seventy adults aged 50 and older completed the 4
      item Perceived Stress Scale and measures of verbal fluency, immediate and delayed
      word recall 2 years apart. A first differences regression model revealed that the
      change in stress over 2 years was inversely associated with a change in immediate
      word recall performance, even after adjustment for change in possible confounders
      (B = -0.030, 95% CI [-.056, -.004], p < .05). No association was observed for
      delayed recall or verbal fluency performance. Change in perceived stress is
      inversely correlated with change in immediate recall, even over a short period.
      Stress modifying interventions could potentially reduce the risk of cognitive
      decline associated with ageing.

PMID- 29380934
TI  - Semiconducting polymer nanoparticles for amplified photoacoustic imaging.
AB  - Semiconducting polymer nanoparticles (SPNs) are a new class of photonic materials
      with great potential for biomedical applications. Owing to their large absorption
      coefficients, tunable optical properties, and high photostability, SPNs have
      recently been used to improve the sensitivity and resolution of photoacoustic
      (PA) imaging. In particular, a number of strategies have been explored to design
      activatable SPNs for amplified in vivo PA imaging. In this review, the recent
      advances in the development of SPNs as exogenous PA contrasts agents have been
      summarized and their promising potential as multifunctional probes for cancer
      theranostics has been discussed. This article is categorized under: Diagnostic
      Tools > In Vivo Nanodiagnostics and Imaging.

PMID- 29380935
TI  - Reactions to psychological contract breaches and organizational citizenship
      behaviours: An experimental manipulation of severity.
AB  - Grounded in affective events theory, we investigated the effects of
      experimentally manipulated psychological contract breaches on participants'
      feelings of violation, subsequent perceptions of psychological contract strength,
      and organizational citizenship behaviours in a sample of working adults. Results
      support previous findings that pre-existing relational psychological contract
      strength interacts with severity of unmet promises or expectations. Specifically,
      individuals with high relational contracts who experience low severity of unmet
      promises/expectations have the lowest breach perceptions, whereas individuals
      with high relational contracts who experience more severe levels unmet
      promises/expectations experience the highest level of breach perceptions. Results
      also support the concept of a breach spiral in that prior perceptions of breach
      led to an increased likelihood of subsequent perceptions of breach following the
      experimental manipulation. Furthermore, consistent with affective events theory,
      results support the argument that a psychological contract breach's effect on
      specific organizational citizenship behaviours is mediated by feelings of
      violation and the reassessment of relational contracts. These effects were
      present even after controlling for the direct effects of the manipulated severity
      of unmet promises/expectations.

PMID- 29380936
TI  - A retrospective case-control analysis of the efficacy of Gardasil(r) vaccination
      in 28 patients with recurrent respiratory papillomatosis of the larynx.

PMID- 29380937
TI  - Sulforaphane Improves Abnormal Lipid Metabolism via Both ERS-Dependent XBP1/ACC
      &SCD1 and ERS-Independent SREBP/FAS Pathways.
AB  - SCOPE: To investigate the effect of sulforaphane (SFN) on the abnormal lipid
      metabolism and underlying mechanisms. METHODS AND RESULTS: Models with abnormal
      lipid metabolism are established both in rats and human hepatocytes. Hepatic
      steatosis is detected by hematoxylin and eosin and oil red O staining. The
      structure of endoplasmic reticulum is visualized by transmission electron
      microscopy. The expressions of X-box binding protein 1 (XBP1), protein kinase
      like ER kinase (PERK), sterol regulatory element binding protein-1c (SREBP1c),
      and lipogenic enzymes are determined by real-time PCR and western blot analysis.
      SFN lowers the content of triglyceride and cholesterol. SFN alleviates the
      swelling of ER and decreases the perimeter of ER. SFN significantly decreases the
      expressions of acetyl CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase 1 (SCD1),
      and fatty acid synthase. SFN inhibits SREBP1c by blocking the PERK. Meanwhile,
      SFN suppresses ACC1 and SCD1 via blocking the formation of splicing-type XBP1.
      The key roles of XBP1 and SREBP1c in SFN-reduced lipid droplets are confirmed by
      a timed sequence of measurement according to time points. CONCLUSION: SFN
      improves abnormal lipid metabolism via both ER-stress-dependent and -independent
      pathways.

PMID- 29380938
TI  - Deprivation in relation to urgent suspicion of head and neck cancer referrals in
      Glasgow.
AB  - AIM: To examine deprivation measured by the Scottish index of multiple
      deprivation (SIMD) and its relation to urgent suspicion of head and neck cancer
      referrals. A secondary aim was to examine the symptomatology generating urgent
      suspicion of cancer (USOC) referrals by SIMD category. METHODS: All "urgent
      suspicion of cancer" referrals to the GGC ENT department over a one-year period,
      between 2015 and 2016, were reviewed. Information was recorded anonymously and
      included demographics and red flag referral symptoms. RESULTS: A total of 1998
      patients were assessed, 43.4% (n = 867) were male. A total of 171 (8.6%) patients
      had primary head and neck cancer. A total of 61 patients had other types of
      cancer, giving an all cause cancer rate of 11.6%. About 71.3% of primary patients
      with head and neck cancer (HNC) were male. The most common SIMD category observed
      was SIMD1, the most common SIMD category yielding a primary head and neck cancer
      diagnosis was SIMD1. Neck lump was the commonest symptom amongst all SIMD
      categories. CONCLUSION: A link between deprivation and USOC referrals has been
      established. A difference in gender distribution between referrals and HNC was
      observed, more females are referred but a significantly higher number of patients
      with HNC are males. Neck lump is a very strong referral indicator for HNC and
      intermittent hoarseness is not. The findings from this analysis could be used to
      refine local referral patterns and priority of referral.

PMID- 29380939
TI  - Electromagnetic Shielding Materials in GHz Range.
AB  - The state-of-the art in the design and the manufacture methods of the different
      electromagnetic shielding materials has been reviewed. This topic has become a
      mainstream field of research because of the electromagnetic pollution generated
      by telecommunication technology development. The review is centred in absorbent
      materials and shows a general overview of how the absorption properties of such
      composites can be tailored through changes in geometry, composition, morphology,
      and the filler particles content. Although different types of materials are
      explained, the text is mainly focused on carbon materials such as graphene and
      carbon nanotubes. In this way, the importance of the dispersion of the conductive
      fillers in different polymer matrices is discussed. In addition, an extensive
      study on new complex architectures such as foam-based materials is presented.
      Finally, the combination of carbon fillers with other constituents such as
      metallic nanoparticles is mentioned. In all these studies, the efficiency of the
      composites as absorbent or reflective of electromagnetic radiation is discussed.

PMID- 29380940
TI  - Stage of obesity epidemic model: Learning from tobacco control and advocacy for a
      framework convention on obesity control.
AB  - The 2011 United Nations political declaration against non-communicable diseases
      (NCDs) targeted four major risk factors: tobacco use, harmful use of alcohol, an
      unhealthy diet, and a lack of physical activity. The Framework Convention on
      Tobacco Control (FCTC), MPOWER strategies, and the four-stage model of the
      tobacco epidemic are useful references for the prevention and control of other
      risk factors and NCDs. Obesity control is a more complex challenge. Herein we
      propose a stage of obesity epidemic model (SOEM). Obesity is in the early stages
      in most countries with increasing prevalence, but its effects on mortality will
      increase rapidly, even if its prevalence may have reached a peak and be
      declining. Based on current relative risk, obesity kills one in three obese
      people. Like tobacco, epidemiological studies of obesity in the early stages
      would underestimate the risks and disease burden. Further research will reveal
      more harm, especially from long-term obesity since childhood. The prevalence of
      obesity will likely overtake smoking prevalence, but commitments to obesity
      control are too weak. The SOEM is needed and should be useful to forewarn against
      the expanding public health problems attributable to obesity, and challenges in
      epidemiology and interventions. Learning from tobacco control, we advocate for a
      framework convention on obesity control. Framing obesity control initiatives in
      the spirit of MPOWER strategies against tobacco should be considered to prevent
      and control obesity and obesity-induced diseases. Healthcare professionals should
      take leading roles in these initiatives and obese individuals should reduce their
      weight and "quit" obesity.

PMID- 29380941
TI  - Management of comedonal acne vulgaris with fixed-combination topical therapy.
AB  - BACKGROUND: Acne vulgaris (acne) is the most common skin disease we see in
      dermatology practice. Clinically, it is characterized by a combination of open
      and closed comedones (formally referred to as noninflammatory lesions) and
      inflammatory papules and pustules. Comedonal acne is more typical in young
      adolescents, but can occur in combination with inflammatory papules and pustules
      at any time. Topical retinoids have long been advocated for the treatment of
      comedonal acne. AIMS: Given the increasing recognition of the inflammatory nature
      of acne and the synergistic benefits seen with fixed combinations we review the
      latest clinical data to provide guidance on optimal management of comedonal acne.
      METHODS: An English language literature search of Medline, EMBASE, and the Web of
      Science using key terms (acne, comedonal, noninflammatory, clinical trials) was
      conducted, and relevant articles reviewed. RESULTS: Comparative data is sparse,
      but we show the importance of fixed combinations with and without retinoids,
      where treatment benefits are comparable. Adapalene 0.1%-benzoyl peroxide 2.5% gel
      has been shown to be comparable to clindamycin 1%-benzoyl peroxide 5% gel, and
      adapalene 0.3%-benzoyl peroxide 2.5% gel. A meta-analysis suggested that
      clindamycin 1.2%-benzoyl peroxide 2.5% gel was more effective than clindamycin
      benzoyl peroxide 5% gel in noninflammatory lesions, and two equivalent clinical
      programs suggest additional benefits of higher doses of benzoyl peroxide (3.75%
      vs 2.5%) in this fixed combination. CONCLUSIONS: Clindamycin 1.2%-benzoyl
      peroxide 3.75% gel may afford similar benefits to adapalene 0.3%-benzoyl peroxide
      2.5% gel in this sometimes difficult to treat patient population.

PMID- 29380942
TI  - Evaluation of a multi-agent chemotherapy protocol combining lomustine,
      procarbazine and prednisolone (LPP) for the treatment of relapsed canine non
      Hodgkin high-grade lymphomas.
AB  - The standard of care treatment for canine lymphoma is multi-agent chemotherapy
      containing prednisolone, cyclophosphamide, vincristine and an anthracycline such
      as doxorubicin (CHOP) or epirubicin (CEOP). Lomustine, vincristine, procarbazine,
      and prednisone (LOPP) has been evaluated as a rescue, with encouraging results;
      however, resistance to vincristine is likely in patients relapsing on CHOP/CEOP,
      and this agent may enhance LOPP toxicity without improving efficacy. The aim of
      this study was to evaluate responses to a modified-LOPP protocol that does not
      include vincristine (LPP) and is administered on a 21-day cycle. Medical records
      of dogs with high-grade multicentric lymphoma from 2012 to 2017 were reviewed.
      Dogs with relapsed lymphoma that received LPP as a rescue protocol were enrolled.
      Response, time from initiation to discontinuation (TTD) and toxicity of LPP were
      assessed. Forty-one dogs were included. Twenty-five dogs (61%) responded to LPP
      including 12 complete responses (CR) and 13 partial responses (PR). Responders
      had a significantly longer TTD (P < .001) compared to non-responders with 84 days
      for CR and 58 days for PR. Neutropenia was documented in 20 dogs (57%): 12 grade
      I to II, 8 grade III to IV. Thrombocytopenia was infrequent (20%): 5 grade I to
      II, 2 grade III to IV. Twelve dogs developed gastrointestinal toxicity (30%): 10
      grade I to II and 2 grade III. Nineteen dogs had elevated ALT (59%): 9 grade I to
      II, 10 grade III to IV. Treatment was discontinued due to toxicity in 8 dogs
      (19%). The LPP protocol shows acceptable efficacy and toxicity-profile and
      minimizes in-hospital procedures.

PMID- 29380943
TI  - Evidence of oxygenic phototrophy in ancient phosphatic stromatolites from the
      Paleoproterozoic Vindhyan and Aravalli Supergroups, India.
AB  - Fossil microbiotas are rare in the early rock record, limiting the type of
      ecological information extractable from ancient microbialites. In the absence of
      body fossils, emphasis may instead be given to microbially derived features, such
      as microbialite growth patterns, microbial mat morphologies, and the presence of
      fossilized gas bubbles in lithified mats. The metabolic affinity of micro
      organisms associated with phosphatization may reveal important clues to the
      nature and accretion of apatite-rich microbialites. Stromatolites from the 1.6 Ga
      Chitrakoot Formation (Semri Group, Vindhyan Supergroup) in central India contain
      abundant fossilized bubbles interspersed within fine-grained in situ-precipitated
      apatite mats with average delta13 Corg indicative of carbon fixation by the
      Calvin cycle. In addition, the mats hold a synsedimentary fossil biota
      characteristic of cyanobacterial and rhodophyte morphotypes. Phosphatic oncoid
      cone-like stromatolites from the Paleoproterozoic Aravalli Supergroup
      (Jhamarkotra Formation) comprise abundant mineralized bubbles enmeshed within
      tufted filamentous mat fabrics. Construction of these tufts is considered to be
      the result of filamentous bacteria gliding within microbial mats, and as
      fossilized bubbles within pristine mat laminae can be used as a proxy for
      oxygenic phototrophy, this provides a strong indication for cyanobacterial
      activity in the Aravalli mounds. We suggest that the activity of oxygenic
      phototrophs may have been significant for the formation of apatite in both
      Vindhyan and Aravalli stromatolites, mainly by concentrating phosphate and
      creating steep diurnal redox gradients within mat pore spaces, promoting apatite
      precipitation. The presence in the Indian stromatolites of alternating apatite
      carbonate lamina may result from local variations in pH and oxygen levels caused
      by photosynthesis-respiration in the mats. Altogether, this study presents new
      insights into the ecology of ancient phosphatic stromatolites and warrants
      further exploration into the role of oxygen-producing biotas in the formation of
      Paleoproterozoic shallow-basin phosphorites.

PMID- 29380944
TI  - Optimal non-invasive diagnosis of fetal achondroplasia combining ultrasonography
      with circulating cell-free fetal DNA analysis.
AB  - OBJECTIVES: To assess the performance of non-invasive prenatal testing (NIPT) for
      achondroplasia using high-resolution melting (HRM) analysis, and to propose an
      optimal diagnostic strategy combining ultrasound examination and cell-free fetal
      DNA (cffDNA) analysis. METHODS: In this prospective multicenter study, cffDNA was
      extracted from blood in pregnant women at risk for fetal achondroplasia (owing to
      paternal achondroplasia, previous affected child or suspected rhizomelic
      shortening) and in pregnant low-risk controls. The presence of either one of the
      two main fibroblast growth factor receptor 3 gene (FGFR3) mutations was
      determined using HRM combined with confirmation by SNaPshot minisequencing.
      Results were compared with phenotypes obtained using three-dimensional computed
      tomography or postnatal examination, and/or molecular diagnosis by an invasive
      procedure. Fetal biometry (head circumference and femur length) was analyzed in
      order to develop a strategy in which cffDNA analysis for diagnosis of
      achondroplasia is offered only in selected cases. RESULTS: Eighty-six blood
      samples from women at risk for fetal achondroplasia and 65 from controls were
      collected. The overall sensitivity and specificity of NIPT were 1.00 (95% CI,
      0.87-1.00) and 1.00 (95% CI, 0.96-1.00), respectively. Critical reduction in
      femur length of affected fetuses could be observed from 26 weeks' gestation.
      CONCLUSION: HRM combined with SNaPshot minisequencing is a reliable method for
      NIPT for achondroplasia. Its implementation in routine clinical care combined
      with ultrasonography is an efficient strategy for the non-invasive diagnosis of
      achondroplasia. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons Ltd.

PMID- 29380945
TI  - Hearing and seeing meaning in noise: Alpha, beta, and gamma oscillations predict
      gestural enhancement of degraded speech comprehension.
AB  - During face-to-face communication, listeners integrate speech with gestures. The
      semantic information conveyed by iconic gestures (e.g., a drinking gesture) can
      aid speech comprehension in adverse listening conditions. In this
      magnetoencephalography (MEG) study, we investigated the spatiotemporal neural
      oscillatory activity associated with gestural enhancement of degraded speech
      comprehension. Participants watched videos of an actress uttering clear or
      degraded speech, accompanied by a gesture or not and completed a cued-recall task
      after watching every video. When gestures semantically disambiguated degraded
      speech comprehension, an alpha and beta power suppression and a gamma power
      increase revealed engagement and active processing in the hand-area of the motor
      cortex, the extended language network (LIFG/pSTS/STG/MTG), medial temporal lobe,
      and occipital regions. These observed low- and high-frequency oscillatory
      modulations in these areas support general unification, integration and lexical
      access processes during online language comprehension, and simulation of and
      increased visual attention to manual gestures over time. All individual
      oscillatory power modulations associated with gestural enhancement of degraded
      speech comprehension predicted a listener's correct disambiguation of the
      degraded verb after watching the videos. Our results thus go beyond the
      previously proposed role of oscillatory dynamics in unimodal degraded speech
      comprehension and provide first evidence for the role of low- and high-frequency
      oscillations in predicting the integration of auditory and visual information at
      a semantic level.

PMID- 29380946
TI  - A fluorescent aptasensor for analysis of adenosine triphosphate based on aptamer
      magnetic nanoparticles and its single-stranded complementary DNA labeled carbon
      dots.
AB  - A new fluorimetric aptasensor was designed for the determination of adenosine
      triphosphate (ATP) based on magnetic nanoparticles (MNPs) and carbon dots (CDs).
      In this analytical strategy, an ATP aptamer was conjugated on MNPs and a
      complementary strand of the aptamer (CS) was labeled with CDs. The aptamer and
      its CS were hybridized to form a double helical structure. The hybridized
      aptamers could be used for the specific recognition of ATP in a biological
      complex matrix using a strong magnetic field to remove the interfering effect. In
      the absence of ATP, no CDs-CS could be released into the solution and this
      resulted in a weak fluorescence signal. In the presence of ATP, the target binds
      to its aptamer and causes the dissociation of the double helical structure and
      liberation of the CS, such that a strong fluorescence signal was generated. The
      increased fluorescence signal was proportional to ATP concentration. The limit of
      detection was estimated to be 1.0 pmol L-1 with a dynamic range of 3.0 pmol L-1
      to 5.0 nmol L-1 . The specific aptasensor was applied to detect ATP in human
      serum samples with satisfactory results. Moreover, molecular dynamic simulation
      (MDS) studies were used to analyze interactions of the ATP molecule with the
      aptamer.

PMID- 29380947
TI  - Photodynamic opening of the blood-brain barrier and pathways of brain clearing.
AB  - A new application of the photodynamic treatment (PDT) is presented for the
      opening of blood-brain barrier (BBB) and the brain clearing activation that is
      associated with it, including the use of gold nanoparticles as emerging
      photosensitizer carriers in PDT. The obtained results clearly demonstrate 2
      pathways for the brain clearing: (1) using PDT-opening of BBB and intravenous
      injection of FITC-dextran we showed a clearance of this tracer via the meningeal
      lymphatic system in the subdural space; (2) using optical coherence tomography
      and intraparenchymal injection of gold nanorods, we observed their clearance
      through the exit gate of cerebral spinal fluid from the brain into the deep
      cervical lymph node, where the gold nanorods were accumulated. These data
      contribute to a better understanding of the cerebrovascular effects of PDT and
      shed light on mechanisms, underlying brain clearing after PDT-related opening of
      BBB, including clearance from nanoparticles as drug carriers.

PMID- 29380948
TI  - Planktonic microbial profiling in water samples from a Brazilian Amazonian
      reservoir.
AB  - Our comprehension of the dynamics and diversity of freshwater planktonic
      bacterial communities is far from complete concerning the Brazilian Amazonian
      region. Therefore, reference studies are urgently needed. We mapped bacterial
      communities present in the planktonic communities of a freshwater artificial
      reservoir located in the western Amazonian basin. Two samples were obtained from
      rainy and dry seasons, the periods during which water quality and plankton
      diversity undergo the most significant changes. Hypervariable 16S rRNA and
      shotgun sequencing were performed to describe the first reference of a microbial
      community in an Amazonian lentic system. Microbial composition consisted mainly
      of Betaproteobacteria, Cyanobacteria, Alphaproteobacteria, and Actinobacteria in
      the dry period. The bacteria distribution in the rainy period was notably absent
      of Cyanobacteria. Microcystis was observed in the dry period in which the gene
      cluster for cyanotoxins was found. Iron acquisition gene group was higher in the
      sample from the rainy season. This work mapped the first inventory of the
      planktonic microbial community of a large water reservoir in the Amazon,
      providing a reference for future functional studies and determining other
      communities and how they interact.

PMID- 29380949
TI  - Vitamin D metabolic loci and preeclampsia risk in multi-ethnic pregnant women.
AB  - Allelic variants in vitamin D metabolism genes may increase the risk of
      preeclampsia, but few studies have systematically tested this hypothesis. Our
      objective was to evaluate the relationship between maternal allelic variants in
      three vitamin D metabolism genes and risk of preeclampsia. Samples were from two
      case-control studies of pregnant women who delivered in Pittsburgh, PA from 1999
      to 2010 and twelve recruiting sites across the United States from 1959 to 1965.
      Single-nucleotide polymorphisms (SNPs) were genotyped 50 kilobases up- and down
      stream in three genes (VDR, GC, and CYP27B1) in the samples from both studies,
      for a total of 744 preeclampsia cases and 2411 controls. Using multivariable
      logistic regression, we estimated the associations between allelic variation in
      each locus and preeclampsia risk by maternal race and study. Meta-analysis was
      used to estimate the association across race-study groups for each SNP. Minor
      allele of a noncoding region of the VDR gene was significantly associated with
      preeclampsia risk, which was verified in the meta-analysis [odds ratio (OR), 95%
      confidence intervals (CI)] after adjusting for multiple comparisons
      [rs12831006:1.5 (1.2, 2.0), P < 0.0001]. The meta-analysis identified
      associations for one intron GC variant [rs843010:1.4 (1.1, 1.9) P < 0.05] and two
      variants of the flanking region of GC [rs842991:1.5 (1.1, 2.0) P < 0.05;
      rs16846876:0.75 (0.58, 0.98) P < 0.05]. There were no statistically significant
      associations for CYP27B1 SNPs. Our results provide additional support for a
      biological role of vitamin D in preeclampsia.

PMID- 29380950
TI  - Sarcoplasmic reticulum Ca2+ -induced Ca2+ release regulates class IIa HDAC
      localization in mouse embryonic cardiomyocytes.
AB  - In embryonic cardiomyocytes, sarcoplasmic reticulum (SR)-derived Ca2+ release is
      required to induce Ca2+ oscillations for contraction and to control cardiac
      development through Ca2+ -activated pathways. Here, our aim was to study how SR
      Ca2+ release regulates cytosolic and nuclear Ca2+ distribution and the subsequent
      effects on the Ca2+ -dependent localization of class IIa histone deacetylases
      (HDAC) and cardiac-specific gene expression in embryonic cardiomyocytes. Confocal
      microscopy was used to study changes in Ca2+ -distribution and localization of
      immunolabeled HDAC4 and HDAC5 upon changes in SR Ca2+ release in mouse embryonic
      cardiomyocytes. Dynamics of translocation were also observed with a confocal
      microscope, using HDAC5-green fluorescent protein transfected myocytes.
      Expression of class IIa HDACs in differentiating myocytes and changes in cardiac
      specific gene expression were studied using real-time quantitative PCR.
      Inhibition of SR Ca2+ release caused a significant decrease in intranuclear Ca2+
      concentration, a rapid nuclear import of HDAC5 and subnuclear redistribution of
      HDAC4. Endogenous localization of HDAC5 and HDAC4 was mostly cytosolic and at the
      nuclear periphery, respectively. Downregulated expression of cardiac-specific
      genes was also observed upon SR Ca2+ release inhibition. Electrical stimulation
      of sarcolemmal Ca2+ influx was not sufficient to rescue either the HDAC
      localization or the gene expression changes. SR Ca2+ release controls subcellular
      Ca2+ distribution and regulates localization of HDAC4 and HDAC5 in embryonic
      cardiomyocytes. Changes in SR Ca2+ release also caused changes in expression of
      the developmental phase-specific genes, which may be due to the changes in HDAC
      localization.

PMID- 29380951
TI  - Effects of short-term sex steroid suppression on dietary fat storage patterns in
      healthy males.
AB  - Hypogonadism in males is associated with increased body fat and altered
      postprandial metabolism, but mechanisms remain poorly understood. Using a cross
      over study design, we investigated the effects of short-term sex hormone
      suppression with or without testosterone add-back on postprandial metabolism and
      the fate of dietary fat. Eleven healthy males (age: 29 +/- 4.5 year; BMI: 26.3 +/
      2.1 kg/m2 ) completed two 7-day study phases during which hormone levels were
      altered pharmacologically to produce a low sex hormone condition (gonadotropin
      releasing hormone antagonist, aromatase inhibitor, and placebo gel) or a
      testosterone add-back condition (testosterone gel). Following 7 days of therapy,
      subjects were administered an inpatient test meal containing 50 MUCi of [1-14 C]
      oleic acid. Plasma samples were collected hourly for 5 h to assess postprandial
      responses. Energy metabolism (indirect calorimetry) and dietary fat oxidation (14
      CO2 in breath) were assessed at 1, 3, 5, 13.5, and 24 h following the test meal.
      Abdominal and femoral adipose biopsies were taken 24 h after the test meal to
      determine uptake of the labeled lipid. Postprandial glucose, insulin, free-fatty
      acid, and triglyceride responses were not different between conditions (P >
      0.05). Whole-body energy metabolism was also not different between conditions at
      any time point (P > 0.05). Dietary fat oxidation trended lower (P = 0.12) and the
      relative uptake of 14 C labeled lipid into femoral adipose tissue was greater (P
      = 0.03) in the low hormone condition. Short-term hormone suppression did not
      affect energy expenditure or postprandial metabolism, but contributed to greater
      relative storage of dietary fat in the femoral depot. ClinicalTrials.gov
      Identifier: NCT03289559.

PMID- 29380952
TI  - Acute ingestion of dietary nitrate increases muscle blood flow via local
      vasodilation during handgrip exercise in young adults.
AB  - Dietary nitrate (NO3-) is converted to nitrite (NO2-) and can be further reduced
      to the vasodilator nitric oxide (NO) amid a low O2 environment. Accordingly,
      dietary NO3- increases hind limb blood flow in rats during treadmill exercise;
      however, the evidence of such an effect in humans is unclear. We tested the
      hypothesis that acute dietary NO3- (via beetroot [BR] juice) increases forearm
      blood flow (FBF) via local vasodilation during handgrip exercise in young adults
      (n = 11; 25 +/- 2 years). FBF (Doppler ultrasound) and blood pressure (Finapres)
      were measured at rest and during graded handgrip exercise at 5%, 15%, and 25%
      maximal voluntary contraction (MVC) lasting 4 min each. At the highest workload
      (25% MVC), systemic hypoxia (80% SaO2 ) was induced and exercise continued for
      three additional minutes. Subjects ingested concentrated BR (12.6 mmol nitrate (n
      = 5) or 16.8 mmol nitrate (n = 6) and repeated the exercise bout either 2 (12.6
      mmol) or 3 h (16.8 mmol) postconsumption. Compared to control, BR significantly
      increased FBF at 15% MVC (184 +/- 15 vs. 164 +/- 15 mL/min), 25% MVC (323 +/- 27
      vs. 286 +/- 28 mL/min), and 25% + hypoxia (373 +/- 39 vs. 343 +/- 32 mL/min) and
      this was due to increases in vascular conductance (i.e., vasodilation). The
      effect of BR on hemodynamics was not different between the two doses of BR
      ingested. Forearm VO2 was also elevated during exercise at 15% and 25% MVC. We
      conclude that acute increases in circulating NO3- and NO2- via BR increases
      muscle blood flow during moderate- to high-intensity handgrip exercise via local
      vasodilation. These findings may have important implications for aging and
      diseased populations that demonstrate impaired muscle perfusion and exercise
      intolerance.

PMID- 29380953
TI  - Nominal carbonic anhydrase activity minimizes airway-surface liquid pH changes
      during breathing.
AB  - The airway-surface liquid pH (pHASL ) is slightly acidic relative to the plasma
      and becomes more acidic in airway diseases, leading to impaired host defense. CO2
      in the large airways decreases during inspiration (0.04% CO2 ) and increases
      during expiration (5% CO2 ). Thus, we hypothesized that pHASL would fluctuate
      during the respiratory cycle. We measured pHASL on cultures of airway epithelia
      while changing apical CO2 concentrations. Changing apical CO2 produced only very
      slow pHASL changes, occurring in minutes, inconsistent with respiratory phases
      that occur in a few seconds. We hypothesized that pH changes were slow because
      airway-surface liquid has little carbonic anhydrase activity. To test this
      hypothesis, we applied the carbonic anhydrase inhibitor acetazolamide and found
      minimal effects on CO2 -induced pHASL changes. In contrast, adding carbonic
      anhydrase significantly increased the rate of change in pHASL . Using pH
      dependent rates obtained from these experiments, we modeled the pHASL during
      respiration to further understand how pH changes with physiologic and
      pathophysiologic respiratory cycles. Modeled pHASL oscillations were small and
      affected by the respiration rate, but not the inspiratory:expiratory ratio.
      Modeled equilibrium pHASL was affected by the inspiratory:expiratory ratio, but
      not the respiration rate. The airway epithelium is the only tissue that is
      exposed to large and rapid CO2 fluctuations. We speculate that the airways may
      have evolved minimal carbonic anhydrase activity to mitigate large changes in the
      pHASL during breathing that could potentially affect pH-sensitive components of
      ASL.

PMID- 29380954
TI  - Mechanical ventilation strategies alter cardiovascular biomarkers in an infant
      rat model.
AB  - Mechanical ventilation (MV) is routinely used in pediatric general anesthesia and
      critical care, but may adversely affect the cardiocirculatory system. Biomarkers
      are increasingly measured to assess cardiovascular status and improve clinical
      treatment decision-making. As the impact of mechanical ventilation strategies on
      cardiovascular biomarkers in ventilated infants is largely unknown, we conducted
      this retrospective study in a healthy in vivo infant rat ventilation model using
      14-days old Wistar rats. We hypothesized that 2 h of mechanical ventilation with
      high and low positive end-expiratory pressure (PEEP), hyperoxemia, hypoxemia,
      hypercapnia, and hypocapnia would significantly impact B-type natriuretic peptide
      (BNP), vascular endothelial growth factor (VEGF), and endothelin-1 (ET-1). We
      found BNP to be driven by both high (9 cmH2 O) and low (1 cmH2 O) PEEP compared
      to ventilated control animals (P < 0.05). VEGF concentrations were associated
      with high PEEP, hyperoxemia, hypoxemia, and hypocapnia (P < 0.05), whereas ET-1
      levels were changed only in response to hypoxemia (P < 0.05). In conclusion, the
      mode of mechanical ventilation alters plasma biomarker concentrations. Moreover,
      BNP and VEGF might serve as surrogate parameters for ventilation induced
      cardiovascular compromise and lung tissue damage. Furthermore, our data support
      the hypothesis, that sudden onset of hyperoxemia may trigger a quick VEGF release
      as a possible cellular survival reflex.

PMID- 29380955
TI  - Endogenous dipeptidyl peptidase IV modulates skeletal muscle arteriolar diameter
      in rats.
AB  - The purpose of this study is to investigate that dipeptidyl peptidase IV (DPP-IV)
      released from skeletal and vascular smooth muscle can increase arteriolar
      diameter in a skeletal muscle vascular bed by reducing neuropeptide Y (NPY)
      mediated vasoconstriction. We hypothesized that the effect of myokine DPP-IV
      would be greatest in the smallest and least in the largest arterioles. Eight male
      Sprague Dawley rats (age 7-9 weeks; mass, mean +/- SD: 258 +/- 41 g) were
      anesthetized and the gluteus maximus dissected in situ for intravital microscopy
      analysis of arteriolar diameter of the vascular network. Computational modeling
      was performed on the diameter measurements to evaluate the overall impact of
      diameter changes on network resistance and flow distribution. In the first set of
      experiments, whey protein isolate powder was added to physiological saline
      solution, put in a heated reservoir, and applied to the preparation to induce
      release of DPP-IV from the muscle. This resulted in an order-dependent increase
      in arteriolar diameter, with the largest change in the 6A arterioles (63% more
      reactive than 1A arterioles; P < 0.05). This effect was abolished by adding the
      DPP-IV inhibitor, Diprotin A. To test if the DPP-IV released was affecting NPY
      mediated vasoconstriction, we applied NPY and whey protein, which resulted in
      attenuated vasoconstriction. These findings suggest that DPP-IV is released from
      muscle and has a unique effect on blood flow, which appears to act on NPY to
      attenuate vasoconstriction. The findings suggest that DPP-IV released from the
      skeletal or smooth muscle can alter muscle blood flow.

PMID- 29380956
TI  - Polyphenol supplementation alters intramuscular apoptotic signaling following
      acute resistance exercise.
AB  - The purpose of this study was to examine the effects of 28-days of
      supplementation with an aqueous proprietary polyphenol blend (PPB) sourced from
      Camellia sinensis on intramuscular apoptotic signaling following an acute lower
      body resistance exercise protocol and subsequent recovery. Untrained males (n =
      38, 21.8 +/- 2.7 years, 173.4 +/- 7.9 cm, 77.6 +/- 14.6 kg) were randomized to
      PPB (n = 14), placebo (PL; n = 14) or control (CON; n = 10). Participants
      completed a lower-body resistance exercise protocol comprised of the squat, leg
      press, and leg extension exercises. Skeletal muscle microbiopsies were obtained
      from the vastus lateralis preexercise (PRE), 1-h (1HR), 5-h (5HR), and 48-h
      (48HR) post-resistance exercise. Apoptotic signaling pathways were quantified
      using multiplex signaling assay kits to quantify total proteins (Caspase 3, 8, 9)
      and markers of phosphorylation status (JNK, FADD, p53, BAD, Bcl-2). Changes in
      markers of muscle damage and intramuscular signaling were analyzed via separate
      repeated measures analysis of variance (ANOVA). Change in Bcl-2 phosphorylation
      at 1H was significantly greater in PL compared to CON (P = 0.001). BAD
      phosphorylation was significantly elevated at 5H in PL compared to PPB (P =
      0.015) and CON (P = 0.006). The change in JNK phosphorylation was significantly
      greater in PPB (P = 0.009), and PL (P = 0.017) compared to CON at 1H, while the
      change for PL was elevated compared to CON at 5H (P = 0.002). A main effect was
      observed (P < 0.05) at 1H, 5H, and 48H for p53 and Caspase 8, with Caspase 3 and
      Caspase 9 elevated at 48H. These data indicate that chronic supplementation with
      PPB alters apoptotic signaling in skeletal muscle following acute muscle-damaging
      resistance exercise.

PMID- 29380960
TI  - e-Inhalers.

PMID- 29380957
TI  - Pilot study: an acute bout of high intensity interval exercise increases 12.5 h
      GH secretion.
AB  - The purpose of this study was to test the hypothesis that high-intensity interval
      exercise (HIE) significantly increases growth hormone (GH) secretion to a greater
      extent than moderate-intensity continuous exercise (MOD) in young women. Five
      young, sedentary women (mean +/- SD; age: 22.6+/-1.3 years; BMI: 27.4+/-3.1 kg/m2
      ) were tested during the early follicular phase of their menstrual cycle on three
      occasions. For each visit, participants reported to the laboratory at 1700 h,
      exercised from 1730-1800 h, and remained in the laboratory until 0700 h the
      following morning. The exercise component consisted of either 30-min of moderate
      intensity continuous cycling at 50% of measured peak power (MOD), four 30-s "all
      out" sprints with 4.5 min of active recovery (HIE), or a time-matched sedentary
      control using a randomized, cross-over design. The overnight GH secretory profile
      of each trial was determined from 10-min sampling of venous blood from 1730-0600
      h, using deconvolution analysis. Deconvolution GH parameters were log transformed
      prior to statistical analyses. Calculated GH AUC (0-120 min) was significantly
      greater in HIE than CON (P = 0.04), but HIE was not different from MOD. Total GH
      secretory rate (ng/mL/12.5 h) was significantly greater in the HIE than the CON
      (P = 0.05), but MOD was not different from CON or HIE. Nocturnal GH secretion
      (ng/mL/7.5 h) was not different between the three trials. For these women, in
      this pilot study, a single bout of HIE was sufficient to increase 12.5 h
      pulsatile GH secretion. It remains to be determined if regular HIE may contribute
      to increased daily GH secretion.

PMID- 29380958
TI  - A single electrical pulse within the protective zone of each cardiac cycle
      prevented reperfusion-induced ventricular tachycardia in conscious mice.
AB  - Early pioneering investigators discovered, in anesthetized dogs, a protective
      period within the cardiac cycle. The protective period was a time within the
      cardiac cycle when a precisely timed stimulus prevented the initiation of
      ventricular fibrillation caused by an earlier stimulus. Thus, in addition to the
      susceptible period of repolarization discussed by Wiggers and Wegria (Am. J.
      Physiol. 131:296, 1940; Am. J. Physiol. 128:500, 1940), there is also a nearby
      protective period. This report describes a protective period within the cardiac
      cycle of conscious mice when a precisely timed stimulus prevented the initiation
      of ventricular tachycardia caused by an earlier stimulus. In addition, we tested
      the hypothesis that this precisely timed pulse within the protective period
      prevents reperfusion-induced ventricular tachyarrhythmias in conscious mice. Mice
      (n = 6) were prepared to record arterial blood pressure and the
      electrocardiogram. In addition, a vascular occluder was placed around the left
      main coronary artery, and stimulating electrodes were secured onto the left
      ventricle. A single precisely timed electrical pulse (5 msec pulse width and 2.5
      V) to the left ventricle arriving 13.9 +/- 1.1 msec after the R-wave, caused
      ventricular tachycardia occurring 24.9 +/- 0.9 msec after the R-wave.
      Importantly, a second precisely timed electrical pulse arriving 18.8 +/- 0.5 msec
      after the first stimulus blocked the induction of ventricular tachycardia caused
      by the earlier stimulus. On an alternate day, the susceptibility to sustained
      ventricular tachycardia produced by 3.5 min of occlusion and reperfusion of the
      coronary artery was determined in conscious mice by use of the vascular occluder.
      Reperfusion resulted in ventricular tachycardia in all six mice. A precisely
      timed pulse within the protective period prevented ventricular tachycardia in all
      mice.

PMID- 29380961
TI  - Experiences of a patient-initiated self-monitoring service in inflammatory
      arthritis: A qualitative exploration.
AB  - OBJECTIVES: The aim of the present study was to explore patients' experience of a
      patient-initiated self-monitoring service for people with rheumatoid or psoriatic
      arthritis who are on methotrexate. METHODS: The study took the form of
      qualitative semi-structured interviews, embedded within a randomized controlled
      trial. Twelve participants who were randomly assigned to the intervention arm
      were interviewed. Interviews digitally, transcribed verbatim and analysed using
      inductive thematic analysis. The study received full National Health Service
      ethics approval from Camden and Islington Community Local Research Ethics
      Committee (Ref. 09/H0722/91). RESULTS: Analysis revealed five key themes.
      Participants described usual care as burdensome and an inefficient use of time,
      particularly those in employment. Being able to self-monitor and initiate their
      own care increased patients' knowledge about their illness and its treatment, and
      enabled them to gain a sense of control and ownership over their arthritis. They
      appreciated the personalized nature of the new service, which allowed them to be
      seen at a time and by a method more appropriate to their needs. There were,
      however, some concerns about fidelity to the service protocol, confusion about
      the lack of consistency between symptoms and laboratory results, and anxiety
      about self-monitoring. CONCLUSIONS: Overall, participants were positive about the
      new service, in comparison with usual care, valuing its tailored approach and
      empowering effects. Further work is needed to ensure adherence to the service
      protocol and address anxieties around self-monitoring prior to any widespread
      implementation of the service.

PMID- 29380962
TI  - Review and action plan for oral health improvement in Sheffield special schools.
AB  - A description of the process of a review of oral health improvement in special
      schools in Sheffield and the implementation of an action plan for these
      activities. Public health competencies encompassed: assessing the evidence on
      oral health and dental interventions, programmes and services; strategic
      leadership and collaborative working for health; oral health improvement.

PMID- 29380964
TI  - ?

PMID- 29380963
TI  - Obesity and Dental Caries in Young Children in Plymouth, United Kingdom: A
      Spatial Analysis.
AB  - OBJECTIVE: To examine the spatial clustering of obesity and dental caries in
      young children in Plymouth, United Kingdom, to evaluate the association between
      these conditions and deprivation, and explore the impact of neighbourhood-level
      characteristics on their distribution. BASIC RESEARCH DESIGN: Cross-sectional
      study analysing data from the National Child Measurement Programme (N=2427) and
      the Local Dental Health Survey (N=1425). The association of deprivation with
      weight status and caries was determined at individual and area level, using ANOVA
      and Poisson models. The overall spatial clustering was assessed using a modified
      version of the Global Moran's I, while clusters were located through Local
      Indicators of Spatial Association. Spatial autocorrelation was assessed using the
      variograms of the raw values. Log-linear Poisson models were fitted to assess the
      significance of neighbourhood characteristics on overweight/obesity and caries
      distribution. RESULTS: At an individual level, deprivation was not associated
      with BMI z-scores but was a significant predictor of caries (p?0.05). However, at
      area level, deprivation related to the rates of both conditions. A significant
      positive autocorrelation was observed across neighbourhoods for caries. The
      variograms suggested spatial autocorrelations up to 2.5 km and 3 km for
      overweight/obesity and caries, respectively. Among several neighbourhood
      characteristics, the proportion of people on benefits was found to be a
      significant predictor of caries rates. CONCLUSIONS: Our results underline the
      importance of considering geographic location and characteristics of the broader
      environment when developing strategies to target obesity and caries.

PMID- 29380966
TI  - ?

PMID- 29380965
TI  - ?

PMID- 29380967
TI  - ?

PMID- 29380968
TI  - ?

PMID- 29380969
TI  - ?

PMID- 29380970
TI  - ?

PMID- 29380971
TI  - ?

PMID- 29380972
TI  - ?

PMID- 29380974
TI  - ?

PMID- 29380973
TI  - ?

PMID- 29380975
TI  - ?

PMID- 29380976
TI  - ?

PMID- 29380978
TI  - ?

PMID- 29380977
TI  - ?

PMID- 29380979
TI  - ?

PMID- 29380980
TI  - ?

PMID- 29380981
TI  - ?

PMID- 29380982
TI  - ?

PMID- 29380983
TI  - ?

PMID- 29380984
TI  - ?

PMID- 29380985
TI  - ?

PMID- 29380986
TI  - ?

PMID- 29380987
TI  - ?

PMID- 29380988
TI  - ?

PMID- 29380989
TI  - ?

PMID- 29380990
TI  - ?

PMID- 29380991
TI  - ?

PMID- 29380992
TI  - ?

PMID- 29380993
TI  - ?

PMID- 29380994
TI  - ?

PMID- 29380995
TI  - ?

PMID- 29380997
TI  - ?

PMID- 29380996
TI  - ?

PMID- 29380998
TI  - ?

PMID- 29380999
TI  - ?

PMID- 29381000
TI  - ?

PMID- 29381001
TI  - ?

PMID- 29381002
TI  - ?

PMID- 29381003
TI  - ?

PMID- 29381004
TI  - ?

PMID- 29381005
TI  - ?

PMID- 29381006
TI  - International Physical Activity Questionnaire for Adolescents (IPAQ A):
      reliability of an Italian version.
AB  - BACKGROUND: Recently a new version of International Physical Activity
      Questionnaire was performed for adolescent (IPAQ-A), but an Italian version lacks
      yet. The aim of the study is to examine the test-retest reliability of an Italian
      version of short IPAQ-A. METHODS: A sample of 10-18-year-old children and
      adolescents was considered. The IPAQ questionnaires were administered twice, the
      second time two days after the first administration. Test-retest reliability and
      internal reliability of the questionnaire were determined using ICC and
      Cronbach's alpha, respectively. RESULTS: 277 questionnaires were collected. The
      response rate was 97% but 57% of the sample completed all the items in the
      questionnaire. 43% of the students have not completed all the items and its age
      distribution shown that 93.5% was in 10-13 years old. Overall internal
      reliability (Cronbach's alpha=0.84) and test-retest reliability for 16 out of 23
      items (ICC>0.70) were high. CONCLUSIONS: The study presents missing and
      unreasonably values. However the study underlines pros and cons of the IPAQ-A:
      high reliability and feasibility to measure the physical activity especially in
      adolescent aged 14-18 years; the IPAQ-A needs of attention and it hasn't to leave
      it to the self-compilation but give support especially in the youngers.

PMID- 29381007
TI  - Acute kidney injury in preterm neonates with <= 30 weeks of gestational age and
      its risk factors.
AB  - BACKGROUND: Acute kidney injury (AKI), an abrupt decline in kidney function, is a
      challenging diagnosis among preterm infants due to some specific features of this
      population. The aim of this study was to determine the risk factors of developing
      AKI and the predictive factors for its severity in preterm neonates with less
      than 31 weeks of gestational age. METHODS: All neonates with less than 31 weeks
      of gestational age, admitted in our NICU between January 2012 and December 2015,
      were included. Maternal and neonatal records about demographics, placental
      abnormalities, perinatal and neonatal period and evolution in NICU, as well as
      electrolytic analysis and serum creatinine and urea values during their
      hospitalization were retrospectively collected and analyzed. RESULTS: A total of
      106 neonates were included. Of those, 24 were diagnosed with AKI, resulting in a
      prevalence of 22.6%, and 82 were used as controls. Gestational age (OR=0.39; 95%
      CI=0.2-0.76; p=0.006), congenital malformations (OR=36.93; 95%CI=2.48-550.59;
      p=0.009), vasoactive drugs (OR=27.06; 95%CI=3.58-204.45; p=0.001), nonsteroidal
      anti-inflammatory drugs (OR=9.61; 95%CI=1.78-51.73; p=0.008) and sepsis (OR=7.78;
      95%CI=1.32-46.04; p=0.024) were found to be independent risk factors. Cardiac
      surgery was a predictive factor for AKI severity (OR=25; 95%CI=2.09-298.29;
      p=0.011). The mortality rate in the AKI group was 41.7%. CONCLUSIONS: AKI in
      preterm neonates is an important feature that contributes to increase the
      mortality in NICUs. Thus, it is crucial to know its risk factors to establish
      prompt diagnosis and prevention and, in this way, be able to improve the
      prognosis.

PMID- 29381008
TI  - Run versus cardiorespiratory endurance- not the same issue?
AB  - BACKGROUND: Obesity is considered as one of the main chronic, non-communicable
      diseases, which has become a global epidemic according to the World Health
      Organization. The present study aim is a detailed analysis of the endurance and
      physical fitness of boys at the age of 10-11-12 years depending on their body
      weight. METHODS: The study group included the total of 71 boys aged 10-12 years,
      who were divided according to the BMI value. All of the boys were subject to the
      cardiorespiratory endurance assessment using the test by Ruffier and the Cooper's
      endurance run. RESULTS: The Cooper and Ruffier test results in the study group
      according to BMI showed that endurance and physical fitness in obese boys was the
      poorest. Physical fitness was equally poor in the other subjects, although the
      level of endurance assessed with the Cooper test was good. CONCLUSIONS:
      Regardless of age, the results of physical fitness were much worse than those of
      endurance in all boys. Even the majority of boys with normal body weight showed
      average results in the endurance test, and bad ones in the physical fitness test.
      Obese subjects showed worse results in case of both of these parameters.

PMID- 29381009
TI  - MW polyomavirus in diarrheal Italian infants.
AB  - BACKGROUND: MXPyV, like MWPyV, was identified in stool samples from children
      suffering diarrhea in Mexico. In this study, we used a home-made real time PCR to
      investigate the presence of this novel viruses in stool specimen collected from
      under-Five- Year-Old Children with gastroenteritis. METHODS: A total of 192 fecal
      specimens previously screened for RV, ADV, NoV, HPeV and SaV, were tested for
      MWPyV with Taqman real time PCR. RESULTS: The most commonly detected virus was
      NoV GII (33.8%), followed by RV (21.3%), SaV (10.9%), HPeV(8%), NoV GI (6.7%) and
      AdV (1%). Real time PCR detected MWPyV in 1/192 (0.5%) patients. CONCLUSIONS: We
      detected MWPyV in 0.5% of fecal specimens collected from pediatric patients
      suffering gastroenteritis which is smaller than the previously reported in
      literature (4.4% in Australia and 12% Mexico).

PMID- 29381010
TI  - Identification of crucial genes of pediatric inflammatory bowel disease in
      remission by protein-protein interaction network and module analyses.
AB  - BACKGROUND: Although the main treatments of inflammatory bowel disease (IBD) aim
      at the induction and maintenance of clinical remission, several studies have
      demonstrated inflammation still present in clinical remission. The goal of this
      study was to analyze the gene expression profiles between the pediatric IBD and
      control samples, aiming to further investigate the underlying therapeutic target
      in remission. METHODS: Gene expression profiles data of GSE33943 were downloaded
      from Gene Expression Omnibus, which included 45 pediatric IBD samples and 13
      control samples. The differentially expressed genes (DEGs) between IBD and
      control samples were identified by LIMMA package in R and the function of DEGs
      were predicted by Gene Ontology and KEGG pathway enrichment analyses using
      GeneAnswer package. Furthermore, a protein-protein interaction (PPI) network was
      constructed through the STRING database and functional module was obtained using
      ClusterONE. RESULTS: A total of 224 DEGs were screened between IBD and control
      samples. These DEGs (e.g. up-regulated FAS and down-regulated CCL5) were mainly
      enriched in cytokine-cytokine receptor interaction and chemokine signaling
      pathway. In addition, some hub genes (e.g. up-regulated PSMA2 and PSMA6) were
      obtained through PPI network and functional module. These two genes were involved
      in Proteasome alpha-subunit and conserved site by functional module analysis.
      CONCLUSIONS: The immune and Proteasome mechanisms are still active during
      remission and FAS, PMSF6 and PMSF2 may be underlying targets for therapy of this
      disease.

PMID- 29381011
TI  - Inflammasome function in monocyte subsets and a risk of late-onset sepsis in
      preterm very low birth weight neonates.
AB  - BACKGROUND: Immature immune systems predispose very low birth weight (VLBW)
      neonates to systemic infections in early life. Defective inflammasome function
      may increase a neonate's susceptibility to late-onset sepsis (LOS). METHODS:
      Blood samples were taken on the 5th day of life (DOL) for all VLBW neonates (non
      LOS and before-LOS groups; n=76), and within 24 hours of sepsis onset (LOS group;
      n=39). Monocyte (MO) subsets and intracellular interleukin-1beta (IL-1beta)
      expression were analysed using flow cytometry. Inflammasome function, defined as
      level of IL-1beta and interleukin-18 (IL-18) was measured with enzyme-linked
      immunosorbent assay. IRA B cells were reported as a fraction of all B cells.
      RESULTS: Stimulation of classical MO in non-LOS cells demonstrated a higher
      expression of intracellular IL-1beta in comparison to MO from before-LOS group.
      Serum from the LOS group revealed a higher level of IL-18. Stimulation of
      mononuclear cultures from samples taken during LOS resulted in significantly
      increased supernatant level of IL-1beta and IL-18 in comparison to samples taken
      on 5th DOL. No changes in the levels of IRA B cells were detected with the onset
      of sepsis. CONCLUSIONS: We did not observe a difference in the functioning of the
      inflammasome within monocytes taken on 5th DOL from premature VLBW neonates.
      Furthermore, there was no observable change in the IRA B cells of the septic and
      non-septic groups. The decreased expression of intracellular IL-1beta within
      classical MO of the before-LOS group may be an independent risk factor for LOS
      development.

PMID- 29381012
TI  - Does an increase in vitamin D concentrations have a clear positive significance
      in reducing the SCORing atopic dermatitis scores in children with atopic
      dermatitis?

PMID- 29381013
TI  - Forgotten children in parked vehicles: a review of Italian fatalities.
AB  - BACKGROUND: In recent years, Italy has reported the deaths of children who have
      died of hyperthermia after having been left inadvertently in a car seat. Although
      very rare, these preventable deaths have dramatic and longlasting consequences
      for families, communities and public opinion. The aim of the paper is to review
      the available data on the deaths of children in vehicles by heatstroke in Italy
      and to discuss how to promote strategies aimed at avoiding these preventable
      fatalities. METHODS: We carried out a search using the website research tool for
      the five most widelyread Italian newspapers and an internet search on Google and
      Yahoo's Italian websites, to identify lethal cases of children left
      unintentionally in a parked motor vehicle. RESULTS: We identified eight deaths,
      occurring between 1998 and 2017 in Italy. All incidents occurred in the period
      between May and July when the mean daily external temperature was between 16 and
      27.5 degrees  C. Five girls and three boys between 11 and 24 months in age were
      involved, and in all cases the caregiver concerned was a parent. CONCLUSIONS: The
      Public Health community must vigorously promote research by auto manufacturers to
      develop technological solutions such as visual and audio warning systems aimed at
      reducing the possibility that a child be inadvertently left inside a parked
      vehicle.

PMID- 29381014
TI  - [The influence of diets on metabolic processes associated with sirtuin1].
AB  - Over the last decade the investigations of the sirtuin protein family have become
      one of the research priorities. It is connected with the fact that sirtuins play
      an important role as regulators of cell homeostasis in mammals. Sirtuins can
      regulate metabolism by the influence on some processes in CNS, liver, pancreas,
      musles, adipose tissue. It emphasizes the importance of sirtuins in the
      development of heart diseases, cancer, metabolic syndrome, neurodegenerative and
      some other diseases. Stress factors in particular calorie restriction alter
      sirtuins activity, that leads to some significant alterations of intracellular
      processes: activation of reparation processes, increase of DNA stability,
      elevation of metabolic rate and the lifespan of cells. In this review, we focus
      our attention on the influence of calorie restriction on metabolic alterations
      associated with regulatory role of sirtuin1. Sirtuin1 plays a leading role in
      regulation of cell homeostasis by controlling some important processes, such as
      gene transcription, cell differentiation, stress reaction, inflammation,
      apoptosis, circadian rhythms and life expectancy. We touch briefly on the
      connection between some alterations of diet and the development of stress
      reaction and inflammation. In the review the metabolic alterations in liver,
      pancreas, adipose tissue and central regulatory role of sirtuinl in hypothalamic
      pituitary-adrenal axis connected with calorie restriction are discussed. Sirtuin1
      can be a messenger of some effects of calorie restriction on organism, acting as
      a cell energy sensor. Thus, sirtuinl plays a central role in control and
      modulation of metabolic processes under alterations of diet. Having been one of
      the most important regulator of homeostasis, sirtuinl can be a key element of
      regulation. The influence on this element gives the opportunities of regulation
      of metabolism, calorie restriction effects and creation of new pathogenical
      methods of treatment.

PMID- 29381015
TI  - [Streptozotocin induced diabetes rat models].
AB  - The introduction of chemical compounds in diabetes modeling can't adequately
      reflect the development of the disease. However, the choice of an experimental
      model of diabetes type 1 or 2 is largely determined by the purpose of the
      research: testing of pharmacological activity, genetic research or clarifying the
      mechanisms of disease development. The high cost of respective genetic lines of
      laboratory animals, the complexity of reproduction of the model, the special
      conditions of care and a high degree of inbreeding determine the necessity for
      the development, testing, and improvement of non-genetic models. The most widely
      used chemical models of type 1 diabetes in modern experimental diabetology are
      alloxan models and of type 2 or mixed type diabetes are streptozotocin models.
      Sensitivity to the introduction of the diabetogenic compounds can essentially
      depend on the species, but also on animal genetic line and its age. The results
      of studies in which the injection of streptozotocin (STZ) to laboratory animals
      (mice and rats) simulated type 2 diabetes are shown. It is noted thatpre
      treatment with nicotinamide can simulate the state more appropriate to type 2
      diabetes. Taking into account the leading role of abdominal obesity as a risk
      factor for type 2 diabetes, considerable attention in the article is paid to the
      modeling of type 2 diabetes by STZ-injection and high-fat diet. As alternative
      models of a type 2 diabetes in rodents also induce by streptozotocin injection
      and high fructose diet. The combined effect of low dose STZ and high fructose
      diet allows in relatively short period induce the development of type 2 diabetes
      in rats. It is concluded that the modeling of diabetes by STZ injection are
      widely demand for the optimization screening of biologically active substances
      with antidiabetic action in experiments in vivo and is a step before their
      clinical trials in the composition of specialized preventive and therapeutic
      products.

PMID- 29381016
TI  - [Functional food in pregnancy].

PMID- 29381017
TI  - [The investigation the combined effect of SNP rs9939609 (gene FTO) and rs4994
      (gene ADRB3) polymorphisms on risk of obesity].
AB  - The genetic factor plays a significant role in the development of obesity, by
      present time the association of hundreds genetic polymorphisms with the risk of
      this disease is established. However, the combined influence of genetic
      polymorphisms remains practically unstudied. We aimed to investigate the combined
      effect SNP rs9939609 (gene FTO) and rs4994 (gene ADRB3) polymorphisms on risk of
      obesity. A case-control study was conducted, including255 obese case (BMI>30
      kg/m2) and 427 non obese controls (BMI<30 kg/m2). Genotyping was performed using
      allele-specific amplification, detection results in real time using TaqMan-probes
      complementary DNA polymorphic sites. It has been shown, that presence of one
      mutant allele of rs9939609 (gene FTO) and rs4994 (gene ADRB3) leads to
      statistically significant association with obesity. Presence of two mutant
      alleles in different polymorphic variants increases risk of obesity by 15%,
      presence of three mutant alleles - by 2.63 fold. The quantity surveyed, suffering
      obesity, increased depending on the number of mutant alleles in studied genetic
      polymorphisms. Presence of one or two mutant alleles in one polymorphic variant
      increased the number of patients with obesity by 13.4%, presence of two or three
      mutant alleles in different polymorphic variants -by 18-19%.

PMID- 29381018
TI  - Prognostic value of preoperative systemic inflammation markers in localized upper
      tract urothelial cell carcinoma: a large, multicenter cohort analysis.
AB  - BACKGROUND: The aim of this study was to investigate the prognostic value of
      preoperative systemic inflammation markers in upper tract urothelial carcinoma
      (UTUC). METHODS: A total of 1137 patients who underwent radical
      nephroureterectomy with bladder cuff excision at 9 institutions from 2004 to
      2015, were retrospectively reviewed. The Glasgow Prognostic Score (GPS), modified
      GPS (mGPS), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte
      ratio (PLR) for each patient were calculated. Univariable and multivariable
      analysis was performed using the Cox proportional hazards regression model. Cut
      off values for NLR and PLR were calculated using a receiver operating
      characteristic curve. RESULTS: The median follow-up period was 39.1
      (interquartile range: 18.3-63.8) months. Univariable analysis revealed that GPS,
      mGPS, PLR, and NLR (all, P=0.001) were significantly associated with both
      recurrence-free survival (RFS) and cancer-specific survival (CSS). Multivariable
      analysis revealed that GPS (P=0.001), PLR (hazards ratio [HR] =1.32; 95% CI: 1.08
      1.62, P=0.007 and HR =1.87; 95% CI: 1.21-2.92, P=0.005), NLR (HR =1.38; 95% CI:
      1.12-1.69, P=0.003 and HR =1.70; 95% CI: 1.10-2.62, P=0.017) were significantly
      associated with RFS and CSS. CONCLUSIONS: Our results suggest that preoperative
      systemic inflammation markers such as GPS, PLR, and NLR are independent
      prognostic factors in patients with UTUC after surgery.

PMID- 29381019
TI  - Bidirectional barbed suture for posterior musculofascial reconstruction and
      knotless vesicourethral anastomosis during robot-assisted radical prostatectomy.
AB  - BACKGROUND: The aim of the work is to describe an original technique of posterior
      musculofascial reconstruction (PMFR) during robot-assisted radical prostatectomy
      (RARP). METHODS: From January 2015 to June 2016, 121 consecutives patients
      underwent RARP and were submitted to a novel technique of PMFR, using a single
      3/0 barbed bidirectional (Filblock(r), Assut Europe) suture. The first step of
      this new technique of PMFR, is to approximate the posterior layer of
      Denonvilliers fascia (DF) to the posterior part of the sphincteric apparatus.
      Then, the second step consists in the anastomosis of the posterior blabber neck
      edge with the posterior urethra edge. We realize the completion of anastomosis
      clockwise from 7 to 12 o'clock and anticlockwise from 5 to 12 o'clock. RESULTS:
      No leakage of anastomosis was observed and the catheter was removed in the 5th
      day after surgery. After catheter removal, the urinary recovery of early
      continence at 3 days was 45% and at 7 days was 75%, while the urinary continence
      recovery at 1 month was 88% and at 3 months was 94%. CONCLUSIONS: In our
      experience this novel approach results feasible in all patient, without extending
      the operation time and gives a good safety in terms of reduction of bleeding and
      leakage with shorter urinary continence recovery's time. The aim of the
      combination of the PMFR and the vesicourethral anastomosis with one bidirectional
      barbed suture is to have all the advantages of both techniques plus the stability
      of a single running suture.

PMID- 29381020
TI  - The role of surgery in the management of metastatic kidney cancer: an evidence
      based collaborative review.
AB  - The current manuscript aims to provide an up to date evidence based analysis on
      the status of surgery in the metastatic renal cell carcinoma setting. It includes
      the role of surgery in the primary tumor as well as recent perspective on the
      surgical management of metastatic disease.

PMID- 29381021
TI  - Aspirin and aggressive prostate cancer in African-American men: only a matter of
      survivin?

PMID- 29381022
TI  - [Nutritional status of patients with different types of gastroesophageal reflux
      disease].
AB  - The aim of the study was to assess dietary intake in patients with erosive (ERD)
      and non-erosive reflux disease (NERD). One hundred and sixty seven patients (103
      women and 64 men, mean age 47+/-13,6 years) were divided according to symptoms
      and endoscopic findings into three groups: 88 patients with NERD, 38 patients
      with ERD and 41 healthy controls. Symptoms were scored by validated GERDQ
      questionnaire, dietary intake was assessed by validated food questionnaire and 24
      h pH/impedance monitoring was used for confirmation of pathological reflux. All
      groups were homogenous by age and sex, both NERD and ERD patients demonstrated
      higher BMI (28.1+/-6.5 vs 28.4+/-6.1 kg/m2) in compare to the patients from
      control group (24.3+/-2.8 kg/m2). Average daily calorie intake was higher in
      patients with NERD and ERD (2579+/-854 vs 2467+/-710 kcal/day) in compare to the
      control group (2093+/-696 kcal/day) due to increased consumption of fat (121+/-52
      vs 112+/-52 g/day) and carbohydrates (244+/-88 vs 216+/-64 g/day) consequently.
      Consumption of dietary fiber was low in all groups in compare to recommended
      daily allowance, but even lower in NERD and ERD patients in compare to control
      (6.0+/-3.8 g/day vs 5.2+/-4.8 g/day vs 9.45+/-5.6 g/day). There was direct
      correlation between gastroesophageal reflux disease (GERD) and average energy
      consumption (R=0.23, p<0.05) and daily total fat consumption (R=0.21, p<0.05),
      but inverse correlation with consumption of dietary fiber (R=-0.23, p<0.05).
      Consumption of alcohol was higher in NERD patients in compare with ERD patients
      and control group (1.2+/-4.9 vs 0.2+/-2.6 vs 0+/-0.87 g/day), but generally it
      was low. Total daily number of refluxes as well as number of acid refluxes were
      highly correlated with daily consumption of energy (R=0.35, p<0.05; R=0.35,
      p<0.05), fat (R=0.33, p<0.05; R=0.32, p<0.05) and protein (R=0.3, p<0.05; R=0.25,
      p<0.05), however inverse correlation was found between total number of refluxes
      and consumption of fibers (R=-0.22, p<0.05). There was no correlation between
      consumption of carbohydrates or alcohol and total number of refluxes or acid
      refluxes. In conclusion, GERD is associated with higher BMI, increased
      consumption of calories and fat and low consumption of dietary fiber. Total
      number of refluxes is related to consumption of fat and fibers. No association
      with consumption of carbohydrates or alcohol was found. These findings need to be
      taken in account for prescription of diet to GERD patients.

PMID- 29381023
TI  - [Promising source of micronutrients for specialized foods with modified
      carbohydrate profile: traditional medicine experience].
AB  - Worldwide experience of Traditional medicine (TM) has been successfully applied
      to the development of modern standardized herbal medicines. Mainly researchers
      are guided by local sources of medicinal plants and traditional medical systems.
      TM experience is also used in the search of plants considered as sources of
      biologically active substances (BAS) and food ingredients. The steady increase in
      the incidence of type 2 diabetes, makes clear the need for research of domestic
      plant sources of BAS (with a proven carbohydrate metabolism effect) to create
      modern specialized foods. This article proves the feasibility of using TM
      experience of Russia and some neighboring European countries (Belarus, Ukraine)
      to develop optimized compositions for specialized food products for patients with
      type 2 diabetes. For reliable identification of the most promising plants, 550
      traditional antidiabetic herbal formulations of 66 traditional recipe directories
      were studied in Russia, Belarus and Ukraine. It revealed 37 species of plants
      included to more than 20% of all bibliographical sources, and 13 plants included
      to more than 50% of prescription directories. The 3 most popular are bilberry
      leaves, leaffruit of common bean, great nettle leaves.

PMID- 29381024
TI  - [Vitamin status of citizens from Moscow Region].
AB  - Evaluation of vitamin status in healthy individuals (68 men and 70 women) aged
      from 18 to 60 years (median - 37 years), residents of Moscow and the Moscow
      region has been performed by means of determination of vitamin C, A, E, B2, B12
      and folic acid level in blood serum. The nutrition was investigated by
      questionnaire method on frequency of food consumption. Both diet of men and women
      had excessive fat content (41.7 and 42.7% of total calories), saturated fatty
      acids (14.1 and 13.6%), added sugars (11.1 and 11.0%), sodium, and had lack of
      dietary fiber (2.5-fold reduced level comparing with RDA). Daily intake of
      vitamin B1 was 1.37+/-0.04 mg for men and 1.06+/-0.07 mg for women, vitamin B2 -
      respectively 1.72+/-0.06 and 1.62+/-0.07 mg, niacin - 18.5+/-0.72 and 14.8+/-0.88
      mg and did not reach the optimal level. All persons were sufficiently supplied
      with vitamins A, C, E and B12: mean and median of blood serum level of retinol,
      tocopherols, ascorbic acid and cobalamins were in the range of optimum values.
      The lack of vitamins A and B12 has not been found in any person. The frequency of
      vitamin C and E insufficiency was insignificant and amounted to 2 and 8%
      respectively. The lack of vitamin B2, and beta-carotene was most pronounced and
      took place in about a half of individuals. Only 34% of healthy people of working
      age were sufficiently supplied with all vitamins. A combined lack of two vitamins
      was detected in 26%, of three vitamins - in 8%. Women were better supplied with
      riboflavin and beta-carotene. The blood serum level of beta-carotene and vitamin
      E was significantly higher in individuals older than 30 years compared with
      persons of younger age. Individuals with overweight or obesity were worse
      supplied with beta-carotene and folate. A negative correlation was detected
      between the levels of serum folate and homocysteine concentration (r=-0.262,
      p<0.05). A positive correlation has been revealed between the concentration of
      folic acid and the level of HDL-C (r=0.356, p<0.01), and iron (r=0.378, p<0.05).

PMID- 29381025
TI  - [Assessment of the using effectiveness of iodine containing additives in
      development of meat products for child nutrition].
AB  - The effectiveness of iodine containing additives on the basis of whey protein and
      milk protein casein compared to iodized salt in the composition of meat minced
      semi-finished products for child nutrition was examined in the experiment on
      laboratory animals. Four variants of the semi-finished products were
      investigated: 1 - control; 2 - enriched with iodine containing milk protein
      casein; 3 - enriched with iodine containing whey proteins; 4 - enriched with
      iodized salt. The semi-finished products were enriched at the level of 15% of the
      daily norm of iodine requirement for children at the age of 7-12 years. Iodine
      content in 100 g of product was 20 MUkg. Rats (initial body weight 140+/-20 g,
      n=80) were divided into five groups (control, intact and three experimental
      groups). Groups 1 and 5 included the animals fed with a standard vivarium diet
      throughout the experiment. The rats from groups 2-4 were fed with the iodine
      enriched diet: group 2 received diet containing semi-finished products No. 2;
      group 3 sample No. 3 and group 4 - sample No. 4. The first stage of the
      experiment was aimed at accumulation of iodine in tissues and organs of animals
      consumed the tested iodine containing additives in the composition of semi
      finished products. The second stage of the experiment consisted in simulation of
      the mercazolilum-induced (50 mg/kg b.w.) hypothyroidism (iodine deficiency) and
      detection of preventive effects of iodine containing meat semi-finished products
      in a model of experimental hypothyroidism in rats. The data obtained upon the end
      of the experiment suggest that the highest effect for correction of iodine
      deficiency was achieved when using the culinary products enriched with iodine
      containing whey proteins (sample No. 3): the level of thyroxine (T4) was restored
      by 98.7% in the animals from group 3 compared to the indices of the intact group,
      T3 by 100%, TSH - by 89.3%. This effect was confirmed by the hematological and
      biochemical blood indexes, as well as the dynamics of their weight change: the
      level of white blood cells was significantly lower by 28%, granulocytes by 44%,
      monocytes by 42% compared to control rats; the weight gain of the animals of the
      3 group was 20.3%, closer to that of intact animals - 26.4%, while in the control
      group it was 2.6 %.

PMID- 29381026
TI  - Tumor-Microenvironment Relaxivity-Changeable Gd-Loaded Poly(L
      lysine)/Carboxymethyl Chitosan Nanoparticles as Cancer-Recognizable Magnetic
      Resonance Imaging Contrast Agents.
AB  - Magnetic resonance imaging (MRI) contrast agents with tumor-microenvironment
      changeable relaxivity are effective to increase the sensitivity and selectivity
      of MRI in tumor diagnosis. In this study, pH-sensitive Gd-loaded Poly(L-lysine)/
      Carboxymethyl Chitosan Nanoparticles (Gd-PCNPs) were developed as relaxivity
      changeable MRI contrast agents based on the "on-off" switchable strategy. The "on
      off" switchable nano-contrast agents were capable of releasing Gd3+ in response
      to physical stimulation, with structure transformed. Gd-PCNPs could responsively
      disassemble in an acidic tumor-microenvironment and increase the exchange of
      protons between water molecules and Gd3+ ions, thus selectively enhance the
      relaxivity in tumor area. Gd-PCNPs were self-assembled via electrostatic
      interaction between poly(L-lysine)-diethylenetriamine pentaacetic acid-gadolinium
      and pH-sensitive carboxymethyl chitosan (CMCS). Gd-PCNPs exhibited spherical
      shape with uniform particle size distribution (166.00 +/- 1 .71 nm) and negative
      zeta potential (-13.2 +/- 4.7 mV). The relaxivity of Gd-PCNPs increased from
      6.618 mM-1 . s-1 to 10.008 mM-1 . s-1 when the pH values decrease from 7.4 to
      6.0, which was higher than Magnevist(r) (3.924 mM-1 . s-1 at both pH 7.4 and 6.0
      (p <0 05). The changeable relaxivity of Gd/PCNPs would result in enhanced
      tumor/normal tissue signal contrast, which was verified by in vivo MRI test. In
      vivo MRI test showed that the signal of Gd-PCNPs was significantly enhanced with
      prolonged imaging time in tumor tissue compared to Magnevist(r) (p <0 05).
      Furthermore, Gd-PCNPs exhibited unobvious in vitro cytotoxicity under the
      experimental concentrations in B16 cells. No obvious damage was observed in the
      different tissues of mice. These results indicated that the relaxivity-changeable
      Gd-PCNPs exhibited demonstrated sensitivity and selectivity in tumor diagnosis
      with a great potential as a novel MRI contrast agent.

PMID- 29381027
TI  - Magnolol Nanoparticles Exhibit Improved Water Solubility and Suppress TNF-alpha
      Induced VCAM-1 Expression in Endothelial Cells.
AB  - The expression of the adhesion molecule vascular cell adhesion molecule-1 (VCAM
      1) on endothelial cells enables the attachment of leukocytes to the endothelium,
      which may lead to inflammation and the development of atherosclerosis. Magnolol
      is a major bioactive compound derived from the plant species Magnolia
      officinalis. In this study, we synthesized a novel nanoparticle formulation of
      magnolol to improve its water solubility and physicochemical properties,
      evaluated its effects on TNF-alpha-induced VCAM-1 expression in endothelial
      cells, and determined the signal transduction pathways involved. Our findings
      demonstrated that the magnolol nanoparticle system showed great improvements in
      physicochemical properties and water solubility owing to a reduction in particle
      size, transformation from a crystalline to amorphous structure, and the formation
      of hydrogen bonds with the nanoparticle carriers. In terms of its biological
      actions, magnolol nanoparticles attenuated TNF-alpha-induced VCAM-1 protein
      expression, promoter activity, and mRNA expression in endothelial cells in vitro.
      This was found to be mediated by the ERK, AKT, and NF-kappaB signaling pathways.
      In addition, magnolol nanoparticles inhibited TNF-alpha-induced leukocyte
      adhesion to endothelial cells, and suppressed TNF-alpha-induced VCAM-1 expression
      in the aortic endothelium of mice. In summary, since magnolol nanoparticles
      inhibit endothelial VCAM-1 expression and leukocyte adhesion to endothelial
      cells, this novel drug formulation may be a potentially useful therapeutic
      formulation to prevent the development of atherosclerosis and inflammatory
      diseases.

PMID- 29381028
TI  - Current evidence for the safety and efficacy of the bio-engineered dual therapy
      COMBO stent.
AB  - The novel dual-therapy COMBO stent aims to promote vessel healing after
      percutaneous coronary intervention (PCI) in patients with coronary artery
      disease. The pro-healing technique consists of an anti-CD34+ antibody layer that
      attracts circulating endothelial progenitor cells (EPCs), which bind to the stent
      surface and allow rapid endothelialization by differentiation of the EPCs into
      normal endothelial cells. The COMBO stent combines this pro-healing technique
      with an abluminal drug elution of sirolimus. The promise of this dual-therapy
      stent is that it may safely allow a shortened duration of dual-antiplatelet
      therapy (DAPT) after stent placement. Moreover, with a mature endothelial layer,
      lower rates of in-stent restenosis may be expected. Clinical outcomes after COMBO
      stent implantation have been recently evaluated in both randomized trials and
      large, prospective, multicenter registries, showing low clinical event rates of
      in-stent restenosis and stent thrombosis. Randomized clinical trials (HARMONEE
      and RECOVERY) have demonstrated the non-inferiority of COMBO versus "first in
      class" second generation and newer generation drug-eluting stents. Safety and
      efficacy of 3 months of DAPT after COMBO stent placement in patients presenting
      with acute coronary syndrome has been evaluated in the large REDUCE randomized
      controlled trial, showing non-inferiority to standard duration of 12-month DAPT.
      In this review we provide an overview of the current pre-clinical and clinical
      evidence for the performance of the COMBO stent.

PMID- 29381031
TI  - A Medicare appeal for CGM coverage: one patient's never-ending story.
AB  - The author, who has lived with type 1 diabetes for more than 50 years, shares his
      account of a successful appeal of Medicare's policy of refusing to pay for
      continuous glucose monitoring (CGM).

PMID- 29381029
TI  - Efficient Direct Lineage Reprogramming of Fibroblasts into Induced Cardiomyocytes
      Using Nanotopographical Cues.
AB  - Induced cardiomyocytes (iCMs) generated via direct lineage reprogramming offer a
      novel therapeutic target for the study and treatment of cardiac diseases.
      However, the efficiency of iCM generation is significantly low for therapeutic
      applications. Here, we show an efficient direct conversion of somatic fibroblasts
      into iCMs using nanotopographic cues. Compared with flat substrates, the direct
      conversion of fibroblasts into iCMs on nanopatterned substrates resulted in a
      dramatic increase in the reprogramming efficiency and maturation of iCM
      phenotypes. Additionally, enhanced reprogramming by substrate nanotopography was
      due to changes in the activation of focal adhesion kinase and specific histone
      modifications. Taken together, these results suggest that nanotopographic cues
      can serve as an efficient stimulant for direct lineage reprogramming into iCMs.

PMID- 29381032
TI  - Diabetes and Medicare competitive bidding: the "perfect storm" for patient harm.
AB  - A recent Diabetes Care study found flaws in Medicare's competitive bidding
      program for diabetes test strips. Two of that study's co-authors discuss the
      findings and why CMS should suspend the bidding program.

PMID- 29381030
TI  - Cationic Polyarginine Conjugated Mesoporous Bioactive Glass Nanoparticles with
      Polyglycerol Coating for Efficient DNA Delivery.
AB  - Mesoporous bioactive glass (MBG) is a type of material with high biological
      activity and excellent biocompatibility. Because of its high specific surface
      area and adjustable surface morphology, MBG is usable for loading and delivering
      molecules. In our previous report, MBG particles were used as gene vectors and
      showed good transfection rate. In this paper, MBG, prepared through a sacrificial
      liquid template method in sol-gel process, was covered with polyglycerol (PG) and
      the resulting MBG-PG was further functionalized with octaarginine (Arg8. More
      specifically, MBG-PG-Arg8 particles were synthesized by PG functionalization of
      MBG through ring-opening polymerization of glycidol on the MBG surface, followed
      by multistep organic transformations (-OH-> -OTs (tosylate)-> -N3 in the PG layer
      and click conjugation of the Arg8 terminated with propargyl glycine. MBG-PG-Arg8
      was successfully taken up by cells more efficiently due to the cellpenetrating
      property of Arg8, and thus showed higher plasmid DNA loading and cell
      transfection efficiency than MBG modified with amino groups. This novel arginine
      functionalized MBG may be a good candidate as a vector for gene delivery with
      higher efficiency.

PMID- 29381033
TI  - Quality measure improvement strategies for elderly patients with diabetes.
AB  - The authors discuss a simple strategy for payers to ensure more patients with
      type 2 diabetes achieve control of A1C.

PMID- 29381034
TI  - Florida Blue program focuses on weight loss - and fun - to prevent type 2
      diabetes in older adults.
AB  - How does the largest payer in a state with a large senior population respond to
      the rising need for diabetes care and prevention?

PMID- 29381035
TI  - History lessons in innovation: digital behavioral medicine can address the
      diabetes "double epidemic" facing Medicare and America's seniors.
AB  - Now that Medicare is poised to pay for the Diabetes Prevention Program, the next
      question is how to make it scalable.

PMID- 29381036
TI  - Comprehensive medication management services: benefits for seniors with diabetes.
AB  - Authors from the University of Minnesota College of Pharmacy highlight the role
      that pharmacists can play in care optimization for seniors with chronic
      conditions.

PMID- 29381037
TI  - Technology, seniors, and sense making.
AB  - As primary care physicians and leaders of Wellframe, a mobile health company
      working with payers and physicians groups to extend care between visits for
      patients with complex comorbidities, Drs Panch and Goodman discuss their
      experiences building a mobile application used by elderly patients to communicate
      with clinicians and manage chronic disease.

PMID- 29381038
TI  - Widespread adoption of evidence-based practices is essential for a growing
      Medicare population.
AB  - When providers move from employing traditional practices to new methods that are
      steeped in evidence, this benefits patient health. The result is higher-quality,
      more affordable care, often stemming from lower rates of hospital infections,
      readmissions, and, in general, improved outcomes.

PMID- 29381039
TI  - Foot and Ankle Conditions: Foreword.

PMID- 29381040
TI  - Foot and Ankle Conditions: Plantar Fasciitis.
AB  - Plantar fasciitis is the most common cause of heel pain in adults. It involves
      painful symptoms occurring along the plantar fascia with or without the presence
      of a bony heel spur. Heel pain that occurs on standing after a prolonged non
      weight-bearing period is a prominent symptom of plantar fasciitis. On physical
      examination, palpation along the medial plantar calcaneal region reproduces the
      painful symptoms. Routine imaging studies usually are not necessary but can be
      used to rule out pathologies or confirm chronic or recalcitrant plantar
      fasciitis. The presence of a heel spur on x-ray is not thought to be an
      underlying cause of symptoms and indicates the condition has been present for at
      least 6 to 12 months. Conservative therapies such as rest, ice massage,
      nonsteroidal anti-inflammatory drugs, specific plantar fascia stretching
      exercises, and orthoses are the preferred initial treatments. Injection therapies
      using a corticosteroid or platelet-rich plasma typically provide short-term
      relief. If conservative treatment is ineffective, extracorporeal shock wave
      therapy and surgery may be considered.

PMID- 29381041
TI  - Foot and Ankle Conditions: Pes Planus.
AB  - Pes planus or pes planovalgus (ie, flatfoot) is a common condition among young
      children and also is encountered in adults. In children, congenital pes planus
      typically resolves with age as the foot musculature strengthens. Flexible pes
      planus is defined as a normal arch during non-weight-bearing activity or
      tiptoeing, with a flattening arch on standing. In rigid pes planus, the arch
      remains stiff and collapsed with or without weight bearing. Patients with rigid
      pes planus should be referred for subspecialist treatment. Patients with flexible
      pes planus, in the absence of signs of rheumatologic, neuromuscular, genetic, or
      collagen conditions, should be treated conservatively. Asymptomatic children
      should be monitored and maintenance of a healthy weight should be encouraged.
      Surgical intervention for refractory symptomatic pediatric pes planus may be
      considered but there is little evidence to support it. Several etiologies of
      acquired pes planus in adults have been identified. The most common is posterior
      tibial tendon dysfunction. Clinical and x-ray evaluation can assist in staging
      the condition and guiding treatment decisions.

PMID- 29381042
TI  - Foot and Ankle Conditions: Chronic Lateral Ankle Pain.
AB  - Chronic ankle pain is relatively common in family medicine. Sequelae from lateral
      ankle sprains are the most common cause. Other etiologies include peroneal
      tendinopathy or subluxation, osteochondral injury, lateral ankle impingement,
      sinus tarsi syndrome, cuboid syndrome, bony stress injury, and other unusual
      factors. A thorough history focusing on the mechanism of injury (if traumatic)
      and the nature of the pain along with a targeted physical examination typically
      will provide the information needed to make the diagnosis. Imaging might be
      necessary for diagnosis or confirmation of the diagnosis. Early functional
      bracing, physical therapy for strengthening, and proprioceptive exercises are the
      preferred treatments for most patients. Daily pain drugs or full immobilization
      devices rarely are necessary.

PMID- 29381043
TI  - Foot and Ankle Conditions: Midfoot and Forefoot Conditions.
AB  - The midfoot and forefoot are the regions of the foot distal to the talus and
      calcaneus and are critical to weight bearing and movement. They help support the
      arch of the foot, provide shock absorption, and convert vertically oriented
      forces into horizontal forward and propulsive movement. A spectrum of acute,
      subacute, and chronic conditions in these regions can cause pain and decreased
      function. A thorough history and physical examination should include foot and leg
      biomechanics, alignment, and posture in addition to palpation of painful areas.
      All patients with traumatic or overuse midfoot and forefoot injuries should be
      evaluated with x-rays, with the need for advanced imaging determined based on
      initial findings. Appropriate diagnosis and management of Lisfranc joint injuries
      and navicular and base of the fifth metatarsal stress fractures can prevent
      adverse outcomes. Management of these injuries commonly includes a period of non
      weight-bearing immobilization and referral to an orthopedic surgeon. Turf toe,
      hallux rigidus, metatarsalgia, and Morton neuroma are common causes of forefoot
      pain. Treatment should be individualized and may include shoe and orthotic
      adjustments, injections, and, occasionally, surgical intervention.

PMID- 29381044
TI  - Ultraefficient Ultraviolet and Visible Light Sensing and Ohmic Contacts in High
      Mobility InSe Nanoflake Photodetectors Fabricated by the Focused Ion Beam
      Technique.
AB  - A photodetector using a two-dimensional (2D) low-direct band gap indium selenide
      (InSe) nanostructure fabricated by the focused ion beam (FIB) technique has been
      investigated. The FIB-fabricated InSe photodetectors with a low contact
      resistance exhibit record high responsivity and detectivity to the ultraviolet
      and visible lights. The optimal responsivity and detectivity up to 1.8 * 107 A W
      1 and 1.1 * 1015 Jones, respectively, are much higher than those of the other 2D
      material-based photoconductors and phototransistors. Moreover, the inherent
      photoconductivity (PC) quantified by the value of normalized gain has also been
      discussed and compared. By excluding the contribution of artificial parameters,
      the InSe nanoflakes exhibit an ultrahigh normalized gain of 3.2 cm2 V-1, which is
      several orders of magnitude higher than those of MoS2, GaS, and other layer
      material nanostructures. A high electron mobility at room temperature reaching
      450 cm2 V-1 s-1 has been confirmed to be one of the major causes of the inherent
      superior PC in the InSe nanoflakes. The oxygen-sensitized PC mechanism that
      enhances carrier lifetime and carrier collection efficiency has also been
      proposed. This work demonstrates the devices fabricated by the FIB technique
      using InSe nanostructures for highly efficient broad-band optical sensing and
      light harvesting, which is critical for development of the 2D material-based
      ultrathin flexible optoelectronics.

PMID- 29381045
TI  - Mechanism Underlying the Effectiveness of Deferiprone in Alleviating Parkinson's
      Disease Symptoms.
AB  - Elevation in iron content as well as severe depletion of dopamine (DA) as a
      result of iron-induced loss of dopaminergic neurons has been recognized to
      accompany the progression of Parkinson's disease (PD). To better understand the
      mechanism of the mitigating effect of the iron chelator deferiprone (DFP) on PD,
      the interplay between iron and DFP was investigated both in the absence and
      presence of DA. The results show that DFP was extremely efficient in scavenging
      both aqueous iron and iron that was loosely bound to DA with the entrapment of
      iron in Fe-DFP complexed form critical to halting the iron catalyzed degradation
      of DA and associated generation of toxic metabolites. The DFP related scavenging
      of dopamine semiquinone (DA*-) and superoxide (O2*-) may also contribute to its
      positive effects in the treatment of PD.

PMID- 29381046
TI  - A Cleavage-Responsive Stem-Loop Hairpin for Assaying Guide RNA Activity.
AB  - The scope of the CRISPR-Cas9 technology now reaches far beyond genomic
      engineering. While significant efforts are driving the evolution of this
      revolutionary biomedical tool, the in vitro cleavage assay remains the standard
      method implemented to validate the guide RNA that directs endonuclease Cas9 to a
      desired genomic target. Here, we report the development of an alternative guide
      RNA validation system called GUIDER. GUIDER features a hairpin loop structure
      with a proximal guanosine-rich unit, a distal fluorophore unit, and a gRNA
      targeting stem component. Cleavage of GUIDER by its complementary RNA-guided Cas9
      endonuclease complex yields a fluorescent emission at 525 nm, signaling effective
      cleavage of the hairpin structure. GUIDER was validated using the model gene
      target mpcsk9, and it was able to identify the gRNA that could most efficiently
      cleave the target mpcsk9 gene. The modular design of GUIDER should allow it to
      have broad applicability in validating gRNAs, and its fluorescent signal output
      offers a rapid, simple, and quantitative measure of Cas9-mediated DNA cleavage.

PMID- 29381047
TI  - Core Binding Site of a Thioflavin-T-Derived Imaging Probe on Amyloid beta Fibrils
      Predicted by Computational Methods.
AB  - Development of new diagnostic imaging probes for Alzheimer's disease, such as
      positron emission tomography (PET) and single photon emission computed tomography
      (SPECT) probes, has been strongly desired. In this study, we investigated the
      most accessible amyloid beta (Abeta) binding site of [123I]IMPY, a Thioflavin-T
      derived SPECT probe, using experimental and computational methods. First, we
      performed a competitive inhibition assay with Orange-G, which recognizes the
      KLVFFA region in Abeta fibrils, suggesting that IMPY and Orange-G bind to
      different sites in Abeta fibrils. Next, we precisely predicted the IMPY binding
      site on a multiple-protofilament Abeta fibril model using computational
      approaches, consisting of molecular dynamics and docking simulations. We
      generated possible IMPY-binding structures using docking simulations to identify
      candidates for probe-binding sites. The binding free energy of IMPY with the
      Abeta fibril was calculated by a free energy simulation method, MP-CAFEE. These
      computational results suggest that IMPY preferentially binds to an interfacial
      pocket located between two protofilaments and is stabilized mainly through
      hydrophobic interactions. Finally, our computational approach was validated by
      comparing it with the experimental results. The present study demonstrates the
      possibility of computational approaches to screen new PET/SPECT probes for Abeta
      imaging.

PMID- 29381048
TI  - Scandium Terminal Imido Chemistry.
AB  - Research into transition metal complexes bearing multiply bonded main-group
      ligands has developed into a thriving and fruitful field over the past half
      century. These complexes, featuring terminal M?E/M=E (M = transition metal; E =
      main-group element) multiple bonds, exhibit unique structural properties as well
      as rich reactivity, which render them attractive targets for
      inorganic/organometallic chemists as well as indispensable tools for
      organic/catalytic chemists. This fact has been highlighted by their widespread
      applications in organic synthesis, for example, as olefin metathesis catalysts.
      In the ongoing renaissance of transition metal-ligand multiple-bonding chemistry,
      there have been reports of M?E/M=E interactions for the majority of the metallic
      elements of the periodic table, even some actinide metals. In stark contrast, the
      largest subgroup of the periodic table, rare-earth metals (Ln = Sc, Y, and
      lanthanides), have been excluded from this upsurge. Indeed, the synthesis of
      terminal Ln?E/Ln=E multiple-bonding species lagged behind that of the transition
      metal and actinide congeners for decades. Although these species had been pursued
      since the discovery of a rare-earth metal bridging imide in 1991, such a terminal
      (nonpincer/bridging hapticities) Ln?E/Ln=E bond species was not obtained until
      2010. The scarcity is mainly attributed to the energy mismatch between the
      frontier orbitals of the metal and the ligand atoms. This renders the putative
      terminal Ln?E/Ln=E bonds extremely reactive, thus resulting in the formation of
      aggregates and/or reaction with the ligand/environment, quenching the multiple
      bond character. In 2010, the stalemate was broken by the isolation and structural
      characterization of the first rare-earth metal terminal imide-a scandium terminal
      imide-by our group. The double-bond character of the Sc?N bond was unequivocally
      confirmed by single-crystal X-ray diffraction. Theoretical investigations
      revealed the presence of two p-d pi bonds between the scandium ion and the
      nitrogen atom of the imido ligand and showed that the dianionic [NR]2- imido
      ligand acts as a 2sigma,4pi electron donor. Subsequent studies of the scandium
      terminal imides revealed highly versatile and intriguing reactivity of the Sc?N
      bond. This included cycloaddition toward various unsaturated bonds, C-H/Si-H/B-H
      bond activations and catalytic hydrosilylation, dehydrofluorination of fluoro
      substituted benzenes/alkanes, CO2 and H2 activations, activation of elemental
      selenium, coordination with other transition metal halides, etc. Since our
      initial success in 2010, and with contributions from us and across the community,
      this young, vibrant research field has rapidly flourished into one of the most
      active frontiers of rare-earth metal chemistry. The prospect of extending Ln?N
      chemistry to other rare-earth metals and/or different metal oxidation states, as
      well as exploiting their stoichiometric and catalytic reactivities, continues to
      attract research effort. Herein we present an account of our investigations into
      scandium terminal imido chemistry as a timely summary, in the hope that our
      studies will be of interest to this readership.

PMID- 29381049
TI  - Rapid and Efficient Collection of Platinum from Karstedt's Catalyst Solution via
      Ligands-Exchange-Induced Assembly.
AB  - Reported herein is a novel strategy for the rapid and efficient collection of
      platinum from Karstedt's catalyst solution. By taking advantage of a ligand
      exchange reaction between alkynols and the 1,3-divinyltetramethyldisiloxane
      ligand (MViMVi) that coordinated with platinum (Pt(0)), the Karstedt's catalyst
      particles with a size of approximately 2.5 +/- 0.7 nm could be reconstructed and
      assembled into larger particles with a size of 150 +/- 35 nm due to the hydrogen
      bonding between the hydroxyl groups of the alkynol. In addition, because the
      silicone-soluble MViMVi ligand of the Karstedt's catalyst was replaced by water
      soluble alkynol ligands, the resultant large particles were readily dispersed in
      water, resulting in rapid, efficient, and complete collection of platinum from
      the Karstedt's catalyst solutions with platinum concentrations in the range from
      ~20 000 to 0.05 ppm. Our current strategy not only was used for the rapid and
      efficient collection of platinum from the Karstedt's catalyst solutions, but it
      also enabled the precise evaluation of the platinum content in the Karstedt's
      catalysts, even if this platinum content was extremely low (i.e., 0.05 ppm).
      Moreover, these platinum specimens that were efficiently collected from the
      Karstedt's catalyst solutions could be directly used for the evaluation of
      platinum without the need for pretreatment processes, such as calcination and
      digestion with hydrofluoric acid, that were traditionally used prior to testing
      via inductively coupled plasma mass spectrometry in conventional methods.

PMID- 29381050
TI  - Deciphering the Ethylene Carbonate-Propylene Carbonate Mystery in Li-Ion
      Batteries.
AB  - As one of the landmark technologies, Li-ion batteries (LIBs) have reshaped our
      life in the 21stcentury, but molecular-level understanding about the mechanism
      underneath this young chemistry is still insufficient. Despite their deceptively
      simple appearances with just three active components (cathode and anode separated
      by electrolyte), the actual processes in LIBs involve complexities at all length
      scales, from Li+ migration within electrode lattices or across crystalline
      boundaries and interfaces to the Li+ accommodation and dislocation at potentials
      far away from the thermodynamic equilibria of electrolytes. Among all, the
      interphases situated between electrodes and electrolytes remain the most elusive
      component in LIBs. Interphases form because no electrolyte component (salt anion,
      solvent molecules) could remain thermodynamically stable at the extreme
      potentials where electrodes in modern LIBs operate, and their chemical
      ingredients come from the sacrificial decompositions of electrolyte components.
      The presence of an interphase on electrodes ensures reversibility of Li+
      intercalation chemistry in anode and cathode at extreme potentials and defines
      the cycle life, power and energy densities, and even safety of the eventual LIBs
      device. Despite such importance and numerous investigations dedicated in the past
      two decades, we still cannot explain why, nor predict whether, certain
      electrolyte solvents can form a protective interphase to support the reversible
      Li+ intercalation chemistries while others destroy the electrode structure. The
      most representative example is the long-standing "EC-PC Disparity" and the two
      interphasial extremities induced therefrom: differing by only one methyl
      substituent, ethylene carbonate (EC) forms almost ideal interphases on the
      graphitic anode, thus becoming the indispensable solvent in all LIBs manufactured
      today, while propylene carbonate (PC) does not form any protective interphase,
      leading to catastrophic exfoliation of the graphitic structure. With one after
      another hypotheses proposed but none satisfactorily rationalizing this disparity
      on the molecular level, this mystery has been puzzling the battery and
      electrochemistry community for decades. In this Account, we attempted to decipher
      this mystery by reviewing the key factors that govern the interaction between the
      graphitic structure and the solvated Li+ right before interphase formation.
      Combining DFT calculation and experiments, we identified the partial desolvation
      of the solvated Li+ at graphite edge sites as a critical step, in which the
      competitive solvation of Li+ by anion and solvent molecules dictates whether an
      electrolyte is destined to form a protective interphase. Applying this model to
      the knowledge of relative Li+ solvation energy and frontier molecular orbital
      energy gap, it becomes theoretically possible now to predict whether a new
      solvent or anion would form a complex with Li+ leading to desirable interphases.
      Such molecular-level understanding of interphasial processes provides guiding
      principles to the effort of tailor-designing new electrolyte systems for more
      aggressive battery chemistries beyond Li-ion.

PMID- 29381051
TI  - Hyperbranched Triphenylamine Polymer for UltraFast Battery Cathode.
AB  - A novel hyperbranched poly(triphenylamine) (PHTPA) was synthesized, and the
      electrochemical properties of this material were studied. PHTPA was synthesized
      by a facile method in a one-step reaction from affordable monomers. Despite all
      aromatic structures, PHTPA showed good solubility in several organic solvents.
      The battery performance test of PHTPA showed a high discharge voltage, an
      ultrafast charge-discharge performance of 100-300 C, and a long cycle life of
      more than 5000 cycles. Moreover, the addition of the PHTPA to LiFePO4 (LFP)
      improved the charge-transfer resistance and Warburg coefficient, which is related
      to the diffusion of lithium ions in LFP, and consequently improved the charge
      discharge performance of LFP itself at a high C rate (20-100 C). This behavior is
      understood to be the result of the organic-inorganic charge transfer. The
      superior cycle performance of the PHTPA-LFP hybrid cathode was also found. PHTPA
      will serve as an additive for a high-performance LIB.

PMID- 29381052
TI  - The Role of Cations on the Performance of Lithium Ion Batteries: A Quantitative
      Analytical Approach.
AB  - Lithium ion batteries are nowadays the state-of-the-art power sources for
      portable electronic devices and the most promising candidate for energy storage
      in large-size batteries, e.g., pure and hybrid vehicles. However, the degradation
      of the cell components minimizes both storage and operation lifetime (calendar
      and cycle life), which is called aging. Due to the numerous different aging
      effects, in either the single constituents or their interactions with each other,
      many reports about methodologies and techniques, both electrochemical and
      analytical, can be found in the literature. However, quantitative data about the
      degradation effects were seldom stated. One important effect is the cation
      distribution and migration during operation. Metal dissolution and metal
      migration of the cathode and the corresponding deposition of these metals on the
      graphitic anode are known harmful degradation effects, especially for the formed
      solid electrolyte interphase on the surface of the anode. Depending on the
      applied cell chemistries and therefore the cathode material, different mechanisms
      were reported so far. For lithium manganese oxide based cells, the acidification
      of the electrolyte due to composition of the conduction salt is attributed as the
      main source of metal migration. Due to subsequent loss of manganese from the
      cathode, the overall performance of the cell is seriously impaired. Based on the
      obtained observations, this degradation mechanism was adapted to lithium nickel
      cobalt manganese based cells as main cause of the capacity fading. However, with
      the help a developed total X-ray fluorescence method and additional surface and
      electrolyte investigations, the proposed HF based mechanism was disproven.
      Instead, the migration was directly associated with material defects or
      mechanical spalling of the particles. Furthermore, with the obtained quantitative
      data of the migrated transition metals on the anode and separator, the
      contribution on the capacity fade was determined. It ranged only the 0/00 region
      and could therefore be excluded as the main source of the capacity in these
      lithium ion batteries. Nevertheless, the oxidation state of the cations is hardly
      accessible; but would provide further information about the exact migrating
      mechanisms. In addition, lithium can be "lost" or immobilized during
      charge/discharge and is therefore no longer available as an electrochemically
      active cation. For example, the formation, reformation, and growth of the solid
      electrolyte interphase and cathode electrolyte interphase leads to an increased
      active lithium loss during cycling. The investigations on this topic are
      frequently reported in literature; however, quantitative data on the actual
      lithium distribution throughout the cell are relatively few. Furthermore, the
      exact amount of lost lithium in the in the respective interphases is so far not
      available. In order to determine quantitatively the lithium distribution within
      the cell, inductively coupled plasma-based method was applied. For laboratory
      test cells, the lithium that was lost to the housing of the cell was 32 times
      higher than that for pouch bag cells. Furthermore, the determined concentration
      of lithium in the interphases ranged only from 2 to 4%. However, the
      investigations need to be repeated with isotope labeled material (6Li) in order
      to obtain statements that are more precise.

PMID- 29381053
TI  - Hybrid Assembly toward Enhanced Thermal Stability of Virus-like Particles and
      Antibacterial Activity of Polyoxometalates.
AB  - In an effort to improve both the stability of virus-like particles (VLPs) and the
      medical activity of polyoxometalates (POMs), a new hybrid assembly system between
      human papillomavirus (HPV) capsid protein L1 and a europium-containing POM
      (EuW10) has been constructed, for the first time, via the electrostatic
      interactions between them. The co-assembly of EuW10 and HPV 16 L1-pentamer (L1-p)
      in buffer solution resulted in the encapsulation of POMs in the cavity of VLPs,
      which was further confirmed by cesium chloride (CsCl) gradient
      ultracentrifugation, SDS-PAGE, dynamic light scattering, and transmission
      electron microscopy, whereas the post-assembly of EuW10 with the as-prepared VLPs
      leads to the adsorption of POMs only on the external surface of particles, and
      both cases improved the thermal and storage stabilities of VLPs obviously.
      Particularly, the encapsulation of POMs in VLPs largely improved the
      antibacterial activity of EuW10, and thereby, the present study will be
      significant for both the stability improvement of protein vaccines and the
      development of POM medicine.

PMID- 29381054
TI  - Mesh Nanoelectronics: Seamless Integration of Electronics with Tissues.
AB  - Nanobioelectronics represents a rapidly developing field with broad-ranging
      opportunities in fundamental biological sciences, biotechnology, and medicine.
      Despite this potential, seamless integration of electronics has been difficult
      due to fundamental mismatches, including size and mechanical properties, between
      the elements of the electronic and living biological systems. In this Account, we
      discuss the concept, development, key demonstrations, and future opportunities of
      mesh nanoelectronics as a general paradigm for seamless integration of
      electronics within synthetic tissues and live animals. We first describe the
      design and realization of hybrid synthetic tissues that are innervated in three
      dimensions (3D) with mesh nanoelectronics where the mesh serves as both as a
      tissue scaffold and as a platform of addressable electronic devices for
      monitoring and manipulating tissue behavior. Specific examples of
      tissue/nanoelectronic mesh hybrids highlighted include 3D neural tissue, cardiac
      patches, and vascular constructs, where the nanoelectronic devices have been used
      to carry out real-time 3D recording of electrophysiological and chemical signals
      in the tissues. This novel platform was also exploited for time-dependent 3D
      spatiotemporal mapping of cardiac tissue action potentials during cell culture
      and tissue maturation as well as in response to injection of pharmacological
      agents. The extension to simultaneous real-time monitoring and active control of
      tissue behavior is further discussed for multifunctional mesh nanoelectronics
      incorporating both recording and stimulation devices, providing the unique
      capability of bidirectional interfaces to cardiac tissue. In the case of live
      animals, new challenges must be addressed, including minimally invasive
      implantation, absence of deleterious chronic tissue response, and long-term
      capability for monitoring and modulating tissue activity. We discuss each of
      these topics in the context of implantation of mesh nanoelectronics into rodent
      brains. First, we describe the design of ultraflexible mesh nanoelectronics with
      size features and mechanical properties similar to brain tissue and a novel
      syringe-injection methodology that allows the mesh nanoelectronics to be
      precisely delivered to targeted brain regions in a minimally invasive manner.
      Next, we discuss time-dependent histology studies showing seamless and stable
      integration of mesh nanoelectronics within brain tissue on at least one year
      scales without evidence of chronic immune response or glial scarring
      characteristic of conventional implants. Third, armed with facile input/output
      interfaces, we describe multiplexed single-unit recordings that demonstrate
      stable tracking of the same individual neurons and local neural circuits for at
      least 8 months, long-term monitoring and stimulation of the same groups of
      neurons, and following changes in individual neuron activity during brain aging.
      Moving forward, we foresee substantial opportunities for (1) continued
      development of mesh nanoelectronics through, for example, broadening nanodevice
      signal detection modalities and taking advantage of tissue-like properties for
      selective cell targeting and (2) exploiting the unique capabilities of mesh
      nanoelectronics for tackling critical scientific and medical challenges such as
      understanding and potentially ameliorating cell and circuit level changes
      associated with natural and pathological aging, as well as using mesh
      nanoelectronics as active tissue scaffolds for regenerative medicine and as
      neuroprosthetics for monitoring and treating neurological diseases.

PMID- 29381055
TI  - Robust and Mechanically and Electrically Self-Healing Hydrogel for Efficient
      Electromagnetic Interference Shielding.
AB  - Autonomously self-healing hydrogels have received considerable attentions due to
      their capacity for repairing themselves spontaneously after suffering damage,
      which can provide a better stability and a longer life span. In this work, a
      robust and mechanically and electrically self-healing hydrogel with an efficient
      electromagnetic interference (EMI) shielding performance was successfully
      fabricated via the incorporation of multiwalled carbon nanotubes (MWCNTs) into
      the hydrophobically associated polyacrylamide (PAM) hydrogels by using cellulose
      nanofiber (CNF) as the dispersant. It was been found that CNF could not only
      assist the homogeneous dispersion of MWCNTs but also effectively enhance the
      mechanical property of the resultant hydrogels. As a result, the optimal tensile
      strength (~0.24 MPa), electrical conductivity (~0.85 S m-1), and EMI shielding
      effectiveness (~28.5 dB) were achieved for the PAM/CNF/MWCNT composite hydrogels
      with 1 wt % MWCNTs and 0.3 wt % CNF, which showed 458, 844, and 90% increase over
      (~0.043 MPa, ~0.09 S m-1, and ~15 dB, respectively) the PAM hydrogel. More
      encouragingly, these composite hydrogels could rapidly restore their electrical
      conductivity and EMI shielding effectiveness after mechanical damage at room
      temperature without any external stimulus. With outstanding mechanical and self
      healing properties, the prepared composite hydrogels were similar to human skin,
      but beyond human skin owing to their additional satisfactory electrical and EMI
      shielding performances. They may offer promising and broad prospects in the field
      of simulate skin and protection of precision electronics.

PMID- 29381056
TI  - Mechanism for Photopromoted Release of Vanadium from Vanadium Titano-Magnetite.
AB  - The release of V from vanadium titano-magnetite, a predominant natural source of
      V, was studied under light irradiation. The release rate of V from vanadium
      titano-magnetite was accelerated by light irradiation, and the oxidation of V was
      detected. The essence of the photopromoted release of V is that the immobile low
      valence V is transformed to the mobile V(V) by photoinduced active species
      generated from the photocatalysis process of magnetite. Among the photoinduced
      active species, *OH and H2O2 were recognized as the most important oxidizing
      agents. Not only can they directly convert the immobile low-valence V to the
      mobile V(V) but also initiate the Fenton reaction, which produces more *OH and
      then further promotes the oxidation of low-valence V. In addition, a conceptual
      model of the photo promoted release of V was proposed. This study, as part of a
      broader study of the release behavior of V, can improve the understanding of the
      pollution problem about V, as well as the fate and environmental geochemistry
      cycling of V in the natural environment.

PMID- 29381057
TI  - Multivalent Polyaspartamide Cross-Linker for Engineering Cell-Responsive
      Hydrogels with Degradation Behavior and Tunable Physical Properties.
AB  - Hydrogels possess favorable physical properties ideally suited for various
      biotechnology applications. To tailor to specific needs, a number of modification
      strategies have been employed to tune their properties. Herein, a multifunctional
      polymeric cross-linker based on polyaspartamide is developed, which allows for
      the facile adjustment of the type and number of reactive functional groups to fit
      different reaction schemes and control the physical properties of the hydrogels.
      The amine-based nucleophiles containing desired functional groups are reacted
      with polysuccinimide to synthesize polyaspartamide cross-linkers. The cross
      linking density and the concurrent change in mechanical properties of the
      resulting hydrogels are controlled in a wide range only with the degree of
      substitution. This multivalency of the polyaspartamide linkers also induced the
      degradation of hydrogels by the unreacted functional groups on polyaspartamide
      involved in the hydrolysis. Furthermore, the polyaspartamide cross-linker
      conjugated with cell-recognition molecules via the same conjugation mechanism
      (i.e., nucleophilic substitution) render the hydrogels cell-responsive without
      the need of additional processing steps. This versatility of polyaspartamide
      based cross-linker is expected to provide an efficient and versatile route to
      engineer hydrogels with controllable properties for biomedical applications.

PMID- 29381058
TI  - Exploring Two-Dimensional Materials toward the Next-Generation Circuits: From
      Monomer Design to Assembly Control.
AB  - Two-dimensional (2D) materials have attracted tremendous research interest since
      the breakthrough of graphene. Their unique optical, electronic, and mechanical
      properties hold great potential for harnessing them as key components in novel
      applications for electronics and optoelectronics. Their atomic thickness and
      exposed huge surface even make them highly designable and manipulable, leading to
      the extensive application potentials. What's more, after acquiring the
      qualification for being the candidate for next-generation devices, the assembly
      of 2D materials monomers into mass or ordered structure is also of great
      importance, which will determine their ultimate industrialization. By designing
      the monomers and regulating their assembling behavior, the exploration of 2D
      materials toward the next-generation circuits can be spectacularly achieved. In
      this review, we will first overview the emerging 2D materials and then offer a
      clear guideline of varied physical and chemical strategies for tuning their
      properties. Furthermore, assembly strategies of 2D materials will also be
      included. Finally, challenges and outlooks in this promising field are featured
      on the basis of its current progress.

PMID- 29381059
TI  - Multivariate Analysis To Quantify Species in the Presence of Direct Interferents:
      Micro-Raman Analysis of HNO3 in Microfluidic Devices.
AB  - Microfluidic devices are a growing field with significant potential for
      applications to small scale processing of solutions. Much like large scale
      processing, fast, reliable, and cost-effective means of monitoring streams during
      processing are needed. Here we apply a novel micro-Raman probe to the online
      monitoring of streams within a microfluidic device. For either macro- or
      microscale process monitoring via spectroscopic response, interfering or
      confounded bands can obfuscate results. By utilizing chemometric analysis, a form
      of multivariate analysis, species can be accurately quantified in solution
      despite the presence of overlapping or confounding spectroscopic bands. This is
      demonstrated on solutions of HNO3 and NaNO3 within microflow and microfluidic
      devices.

PMID- 29381060
TI  - P-Bodies: Composition, Properties, and Functions.
AB  - Processing bodies (P-bodies) are cytoplasmic ribonucleoprotein (RNP) granules
      primarily composed of translationally repressed mRNAs and proteins related to
      mRNA decay, suggesting roles in post-transcriptional regulation. P-bodies are
      conserved in eukaryotic cells and exhibit properties of liquid droplets. However,
      the function of P-bodies in translational repression and/or mRNA decay remains
      contentious. Here we review recent advances in our understanding of the molecular
      composition of P-bodies, the interactions and processes that regulate P-body
      liquid-liquid phase separation (LLPS), and the cellular localization of mRNA
      decay machinery, in the context of how these discoveries refine models of P-body
      function.

PMID- 29381061
TI  - delta-Selective Functionalization of Alkanols Enabled by Visible-Light-Induced
      Ligand-to-Metal Charge Transfer.
AB  - We demonstrate the application of ligand-to-metal charge transfer (LMCT)
      excitation to the direct catalytic generation of energetically challenging alkoxy
      radicals from alcohols through a coordination-LMCT-homolysis process with an
      abundant and inexpensive cerium salt as the catalyst. This catalytic manifold
      provides a simple and efficient way to utilize the characteristic reactivity and
      selectivity of transient alkoxy radicals for delta-selective C-H bond
      functionalization. Under mild redox-neutral conditions without the need for
      prefunctionalization, this method provides a versatile platform to access
      molecular complexity from simple and abundant alcohols.

PMID- 29381062
TI  - Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological
      Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer
      Cells as Potential Payloads for Antibody-Drug Conjugates.
AB  - Improved, streamlined total syntheses of natural tubulysins such as V (Tb45) and
      U (Tb46) and pretubulysin D (PTb-D43), and their application to the synthesis of
      designed tubulysin analogues (Tb44, PTb-D42, PTb-D47-PTb-D49, and Tb50-Tb120),
      are described. Cytotoxicity evaluation of the synthesized compounds against
      certain cancer cell lines revealed a number of novel analogues with exceptional
      potencies [e.g., Tb111: IC50 = 40 pM against MES SA (uterine sarcoma) cell line;
      IC50 = 6 pM against HEK 293T (human embryonic kidney cancer) cell line; and IC50
      = 1.54 nM against MES SA DX (MES SA with marked multidrug resistance) cell line].
      These studies led to a set of valuable structure-activity relationships that
      provide guidance to further molecular design, synthesis, and biological
      evaluation studies. The extremely potent cytotoxic compounds discovered in these
      investigations are highly desirable as potential payloads for antibody-drug
      conjugates and other drug delivery systems for personalized targeted cancer
      chemotherapies.

PMID- 29381063
TI  - Counterion-Dependent Access to Low-Symmetry Lyotropic Sphere Packings of Ionic
      Surfactant Micelles.
AB  - The water-driven self-assembly of homologous dianionic surfactants into lyotropic
      liquid crystals (LLCs) is investigated, with a focus on understanding how
      surfactant headgroup and counterion identities guide supramolecular spherical
      mesophase selection. Using temperature-dependent small-angle X-ray scattering
      (SAXS), we demonstrate that 2-alkylmalonate surfactants (CnMal-M2) with n = 8
      (octyl) or 10 (decyl) and M = K+, Cs+, or (CH3)4N+ form both simple and complex
      micelle packings. Observed spherical morphologies include body-centered cubic
      (BCC), hexagonally closest-packed (HCP), and tetrahedrally closest-packed Frank
      Kasper (FK) A15 and sigma phases (Pm3(-)n and P42/mnm symmetries, respectively).
      Previously observed in only one other minimally hydrated surfactant, the sigma
      phase is a rare LLC morphology comprising a low-symmetry unit cell containing 30
      sub-2-nm quasispherical micelles, each of which belongs to one of five symmetry
      equivalent classes with discrete aggregation numbers. Temperature versus water
      concentration phase maps for CnMal-M2 LLCs reveal that sigma-phase formation
      depends sensitively on the size and polarizability of the surfactant counterion
      and the length of the surfactant alkyl tail. These observations are rationalized
      in terms of a delicate interplay between global packing symmetry and local
      particle symmetry, and the extent to which counterion-headgroup correlations
      enforce the latter structures in these LLC phases.

PMID- 29381064
TI  - Caged Molecular Glues as Photoactivatable Tags for Nuclear Translocation of
      Guests in Living Cells.
AB  - We developed dendritic caged molecular glues (CagedGlue-R) as tags for nucleus
      targeted drug delivery, whose multiple guanidinium ion (Gu+) pendants are
      protected by an anionic photocleavable unit (butyrate-substituted
      nitroveratryloxycarbonyl; BANVOC). Negatively charged CagedGlue-R hardly binds to
      anionic biomolecules because of their electrostatic repulsion. However, upon
      exposure of CagedGlue-R to UV light or near-infrared (NIR) light, the BANVOC
      groups of CagedGlue-R are rapidly detached to yield an uncaged molecular glue
      (UncagedGlue-R) that carries multiple Gu+ pendants. Because Gu+ forms a salt
      bridge with PO4-, UncagedGlue-R tightly adheres to anionic biomolecules such as
      DNA and phospholipids in cell membranes by a multivalent salt-bridge formation.
      When tagged with CagedGlue-R, guests can be taken up into living cells via
      endocytosis and hide in endosomes. However, when the CagedGlue-R tag is
      photochemically uncaged to form UncagedGlue-R, the guests escape from the
      endosome and migrate into the cytoplasm followed by the cell nucleus. We
      demonstrated that quantum dots (QDs) tagged with CagedGlue-R can be delivered
      efficiently to cell nuclei eventually by irradiation with light.

PMID- 29381065
TI  - Quantification of Major Royal Jelly Protein 1 in Fresh Royal Jelly by
      Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry.
AB  - Major royal jelly protein 1 (MRJP1) is the most abundant protein in royal jelly
      (RJ), and the level of MRJP1 has been suggested as a promising parameter for
      standardization and evaluation of RJ authenticity in quality. Here, a
      quantitative method was developed for the quantification of MRJP1 in RJ based on
      a signature peptide and a stable isotope-labeled internal standard peptide
      FFDYDFGSDER*(R*, 13C6, 15N4) by ultraperformance liquid chromatography-tandem
      mass spectrometry. Recoveries of the established method ranged from 85.33 to
      95.80%, and both the intra- and interday precision were RSD < 4.97%.
      Quantification results showed that content of MRJP1 in fresh RJ was 41.96-55.01
      mg/g. Abnormal levels of MRJP1 were found in three commercial RJs and implied
      that these samples were of low quality and might be adulterated. Results of the
      present work suggested that the developed method could be successfully applied to
      quantify MRJP1 in RJ and also could evaluate the quality of RJ.

PMID- 29381066
TI  - Electronic Properties of Sulfur Covered Ru(0001) Surfaces.
AB  - The structural properties of sulfur superstructures adsorbed on Ru(0001) have
      been widely studied in the past. However, much less effort has been devoted to
      determine their electronic properties. To understand the connection between
      structural and electronic properties, we have carried out density functional
      theory periodic boundary calculations mimicking the four long-range ordered
      sulfur superstructures identified experimentally by means of scanning tunneling
      microscopy (STM) techniques. Our simulations allow us to characterize the nature
      of the sulfur-Ru bond, the charge transfer between the Ru substrate and the
      sulfur adlayers, the interface states, and a parabolic state recently identified
      in STM experiments. A simple analysis, based on a one-dimensional model, reveals
      that this parabolic state is related to a potential well state, formed in the
      surface when the concentration of sulfur atoms is large enough to generate a new
      minimum in the surface potential.

PMID- 29381067
TI  - Neothioviridamide, a Polythioamide Compound Produced by Heterologous Expression
      of a Streptomyces sp. Cryptic RiPP Biosynthetic Gene Cluster.
AB  - During genome mining for thioviridamide-like biosynthetic gene clusters that
      could produce polythioamide RiPP (ribosomally synthesized and post
      translationally modified peptides), we discovered a novel cryptic biosynthetic
      gene cluster. During efforts to express this biosynthetic gene using heterologous
      expression of this biosynthetic gene cluster, a novel compound designated as
      neothioviridamide was produced. We report herein the cloning and heterologous
      expression of the neothioviridamide biosynthetic gene cluster and the isolation,
      structure determination, and cytotoxic activity of neothioviridamide.

PMID- 29381068
TI  - Vibrational Spectroscopy on Photoexcited Dye-Sensitized Films via Pump-Degenerate
      Four-Wave Mixing.
AB  - Molecular sensitization of semiconductor films is an important technology for
      energy and environmental applications including solar energy conversion,
      photocatalytic hydrogen production, and water purification. Dye-sensitized films
      are also scientifically complex and interesting systems with a long history of
      research. In most applications, photoinduced heterogeneous electron transfer
      (HET) at the molecule/semiconductor interface is of critical importance, and
      while great progress has been made in understanding HET, many open questions
      remain. Of particular interest is the role of combined electronic and vibrational
      effects and coherence of the dye during HET. The ultrafast nature of the process,
      the rapid intramolecular vibrational energy redistribution, and vibrational
      cooling present complications in the study of vibronic coupling in HET. We
      present the application of a time domain vibrational spectroscopy-pump-degenerate
      four-wave mixing (pump-DFWM)-to dye-sensitized solid-state semiconductor films.
      Pump-DFWM can measure Raman-active vibrational modes that are triggered by
      excitation of the sample with an actinic pump pulse. Modifications to the
      instrument for solid-state samples and its application to an anatase TiO2 film
      sensitized by a Zn-porphyrin dye are discussed. We show an effective combination
      of experimental techniques to overcome typical challenges in measuring solid
      state samples with laser spectroscopy and observe molecular vibrations following
      HET in a picosecond time window. The cation spectrum of the dye shows modes that
      can be assigned to the linker group and a mode that is localized on the Zn
      phorphyrin chromophore and that is connected to photoexcitation.

PMID- 29381069
TI  - In Situ Infrared Absorption Study of Plasma-Enhanced Atomic Layer Deposition of
      Silicon Nitride.
AB  - Despite the success of plasma-enhanced atomic layer deposition (PEALD) in
      depositing quality silicon nitride films, a fundamental understanding of the
      growth mechanism has been difficult to obtain because of lack of in situ
      characterization to probe the surface reactions noninvasively and the complexity
      of reactions induced/enhanced by the plasma. These challenges have hindered the
      direct observation of intermediate species formed during the reactions. We
      address this challenge by examining the interaction of Ar plasma using atomically
      flat, monohydride-terminated Si(111) as a well-defined model surface and focusing
      on the initial PEALD with aminosilanes. In situ infrared and X-ray photoelectron
      spectroscopy reveals that an Ar plasma induces desorption of H atoms from H
      Si(111) surfaces, leaving Si dangling bonds, and that the reaction of di-sec
      butylaminosilane (DSBAS) with Ar plasma-treated surfaces requires the presence of
      both active sites (Si dangling bonds) and Si-H; there is no reaction on fully H
      terminated or activated surfaces. By contrast, high-quality hydrofluoric acid
      etched Si3N4 surfaces readily react with DSBAS, resulting in the formation of O
      SiH3. However, the presence of back-bonded oxygen in O-SiH3 inhibits H desorption
      by Ar or N2 plasma, presumably because of stabilization of H against ion-induced
      desorption. Consequently, there is no reaction of adsorbed aminosilanes even
      after extensive Ar or N2 plasma treatments; a thermal process is necessary to
      partially remove H, thereby promoting the formation of active sites. These
      observations are consistent with a mechanism requiring the presence of both
      undercoordinated nitrogen and/or dangling bonds and unreacted surface hydrogen.
      Because active sites are involved, the PEALD process is found to be sensitive to
      the duration of the plasma exposure treatment and the purge time, during which
      passivation of these sites can occur.

PMID- 29381070
TI  - Probing the Antiallergic and Anti-inflammatory Activity of Biflavonoids and
      Dihydroflavonols from Dietes bicolor.
AB  - Dietes bicolor (Iridaceae) is an ornamental plant used by African local healers
      to treat diarrhea and dysentery. A new dihydroflavonol, (2R,3R)-3,5,7-trihydroxy
      8-methoxyflavanone (1); two known dihydroflavonols, trans-3-hydroxy-5-methoxy-6,7
      methylenedioxyflavanone (2) and trans-3-hydroxy-5,7-dimethoxyflavanone (3); the
      known isoflavone orobol 7,3'-di-O-methyl ether (4); the known biflavones
      lanaroflavone (5), robustaflavone (6), and amentoflavone (7); and beta-sitosterol
      (8) were isolated from the CH2Cl2 fraction of D. bicolor leaves. The extract
      showed potent activity in antiallergic and anti-inflammatory assays. The
      structures of the isolates were identified by spectroscopic and spectrometric
      methods. Compounds 6 and 7 (400 MUM) exhibited antiallergic activity by
      inhibiting antigen-induced beta-hexosaminidase release at 45.7% and 46.3%,
      respectively. Moreover, 6 and 7 exerted anti-inflammatory activity as
      demonstrated by the inhibition of superoxide anion generation with an IC50 value
      of 1.0 MUM as well as the inhibition of elastase release with IC50 values of 0.45
      and 0.75 MUM, respectively. The anti-inflammatory activity was further explained
      by the virtual docking of the isolated compounds to the binding sites in the
      human neutrophil elastase (HNE) crystal structure using Discovery Studio 2.5. It
      was concluded that the biflavonoids bind directly to HNE and inhibit its
      enzymatic activity based on the CDOCKER algorithm. The data provided evidence for
      the potential use of D. bicolor against certain diseases related to allergy and
      inflammation.

PMID- 29381071
TI  - Electron-Pair Distribution in Chemical Bond Formation.
AB  - The chemical formation process has been studied from relaxation holes, Deltah(u),
      resulting from the difference between the radial intracule density and the
      nonrelaxed counterpart, which is obtained from atomic radial intracule densities
      and the pair density constructed from the overlap of the atomic densities.
      Deltah(u) plots show that the internal reorganization of electron pairs prior to
      bond formation and the covalent bond formation from electrons in separate atoms
      are completely recognizable processes from the shape of the relaxation hole,
      Deltah(u). The magnitude of Deltah(u), the shape of Deltah(u) ? u < Req, and the
      distance between the minimum and the maximum in Deltah(u) provide further
      information about the nature of the chemical bond formed. A computational
      affordable approach to calculate the radial intracule density from approximate
      pair densities has been also suggested, paving the way to study electron-pair
      distributions in larger systems.

PMID- 29381072
TI  - Photocatalytic and Chemoselective Transfer Hydrogenation of Diarylimines in Batch
      and Continuous Flow.
AB  - A visible-light photocalytic method for the chemoselective transfer hydrogenation
      of imines in batch and continuous flow is described. The reaction utilizes Et3N
      as both hydrogen source and single-electron donor, enabling the selective
      reduction of imines derived from diarylketimines containing other reducible
      functional groups including nitriles, halides, esters, and ketones. The dual role
      of Et3N was confirmed by fluorescence quenching measurements, transient
      absorption spectroscopy, and deuterium-labeling studies. Continuous-flow
      processing facilitates straightforward scale-up of the reaction.

PMID- 29381073
TI  - Synthetic-Molecule/Protein Hybrid Probe with Fluorogenic Switch for Live-Cell
      Imaging of DNA Methylation.
AB  - Hybrid probes consisting of synthetic molecules and proteins are powerful tools
      for detecting biological molecules and signals in living cells. To date, most
      targets of the hybrid probes have been limited to pH and small analytes. Although
      biomacromolecules are essential to the physiological function of cells, the
      hybrid-probe-based approach has been scarcely employed for live-cell detection of
      biomacromolecules. Here, we developed a hybrid probe with a chemical switch for
      live-cell imaging of methylated DNA, an important macromolecule in the repression
      of gene expression. Using a protein labeling technique, we created a hybrid probe
      containing a DNA-binding fluorogen and a methylated-DNA-binding domain. The
      hybrid probe enhanced fluorescence intensity upon binding to methylated DNA and
      successfully monitored methylated DNA during mitosis. The hybrid probe offers
      notable advantages absent from probes based on small molecules or fluorescent
      proteins and is useful for live-cell analyses of epigenetic phenomena and
      diseases related to DNA methylation.

PMID- 29381074
TI  - Regioselective Cyclization of (Indol-3-yl)pentyn-3-ols as an Approach to
      (Tetrahydro)carbazoles.
AB  - An acid-catalyzed, highly regioselective cycloisomerization as well as dehydro
      cyclization of (indol-3-yl)pentyn-3-ols has been reported for the selective
      synthesis of tetrahydrocarbazoles and carbazoles. This process is mild and found
      to be very general in terms of structural diversity of substrates. Utilizing the
      strategy, an efficient synthetic approach for the functionalized frameworks of
      carbazomycins A-D has also been developed.

PMID- 29381075
TI  - Regio- and Stereoselective Cascades via Aldol Condensation and 1,3-Dipolar
      Cycloaddition for Construction of Functional Pyrrolizidine Derivatives.
AB  - An efficient and step-economical approach to access functionalized pyrrolizidine
      derivatives by a one-pot tandem sequence, including an aldol condensation and
      subsequent 1,3-dipolar cycloaddition process, has been developed, starting from
      acetone, aldehyde, and proline. A number of substituted aromatic aldehydes were
      amenable to this transformation, and the desired products, racemic 7a-7w and
      chiral 9a-9m, were obtained with excellent regioselectivities and outstanding
      diastereoselectivities. Moreover, in situ NMR studies revealed MgSO4 could
      effectively promote the aldol condensation pathway in this tandem process.

PMID- 29381077
TI  - Brief report: Department of Defense Global, Laboratory-based Influenza
      Surveillance Program's influenza vaccine effectiveness estimates and surveillance
      trends for 2016-2017 influenza season.

PMID- 29381076
TI  - Outbreak of influenza and rhinovirus co-circulation among unvaccinated recruits,
      U.S. Coast Guard Training Center Cape May, NJ, 24 July-21 August 2016.
AB  - Military and Coast Guard recruits are particularly susceptible to respiratory
      infections. Although seasonal influenza vaccinations are mandatory for recruits,
      the vaccine expires annually in June. On 29 July 2016, the U.S. Coast Guard
      Training Center Cape May, NJ, identified an increase in febrile respiratory
      illness (FRI) among recruits. During 24 July-21 August, a total of 115 recruits
      reported symptoms. A total of 74 recruits tested positive for respiratory
      infections: influenza A (H3) (n=34), rhinovirus (n=28), influenza/rhinovirus co
      infection (n=11), and adenovirus/rhinovirus co-infection (n=1), while 41 recruits
      had no laboratory-confirmed specimen but were considered suspected cases. Only
      one recruit reported receiving the seasonal influenza vaccine within the previous
      12 months. Influenza predominated during 24 July-6 August, whereas rhinovirus
      predominated during 7 August-20 August. Most (92.2%) cases were identified in
      four of 10 recruit companies; incidence rates were highest among recruits in
      weeks 2-4 of an 8-week training cycle. Key factors for outbreak control included
      rapid detection through routine FRI surveillance, quick decision-making and
      streamlined response by using a single chain of command, and employing both
      nonpharmaceutical and pharmaceutical interventions.

PMID- 29381078
TI  - Assessment of 12 influenza-like illness case definitions using Department of
      Defense Global, Laboratory-based Influenza Surveillance Program data, 2011-2014.
AB  - Despite the growth in influenza surveillance programs, standardization of a
      globally accepted influenza-like illness (ILI) case definition remains difficult.
      With 2011-2014 Department of Defense Global, Laboratory-based Influenza
      Surveillance Program (DISP) data, 12 case definitions were evaluated using a
      combination of ILI case definitions from the Centers for Disease Control and
      Prevention, World Health Organization, and the DISP. The sensitivity,
      specificity, positive and negative predictive values, and odds ratios for each
      case definition were calculated. Additionally, area under the curve (AUC) was
      calculated for a receiver operating characteristic (ROC) curve to compare the
      case definitions. Between 2 October 2011 and 27 September 2014, 52.3% (5,575 of
      10,662) of respiratory specimens submitted met the inclusion criteria. The case
      definition for the DISP had a sensitivity of 54.6% and specificity of 63.7%. Case
      definitions should be selected according to the objectives of the surveillance
      system and resources available. Sensitive case definitions capture a larger
      proportion of cases but at the cost of testing more specimens. Definitions with
      higher specificity result in fewer false positives but may miss more cases.

PMID- 29381079
TI  - Impact of admission serum calcium levels on mortality in hospitalized patients.
AB  - OBJECTIVES: To assess the relationship between admission serum calcium levels and
      in-hospital mortality in all hospitalized patients. METHODS: All adult
      hospitalized patients who had admission serum calcium levels available between
      years 2009 and 2013 were enrolled. Admission serum calcium was categorized based
      on its distribution into six groups (<7.9, 7.9 to <8.4, 8.4 to <9.0, 9.0 to <9.6,
      9.6 to <10.1, and >=10.1 mg/dL). The odds ratio (OR) of in-hospital mortality by
      admission serum calcium, using the calcium category of 9.6-10.1 mg/dL as the
      reference group, was obtained by logistic regression analysis. RESULTS: 18,437
      patients were studied. The lowest incidence of in-hospital mortality was
      associated with admission serum calcium within 9.6 to <10.1 mg/dL. A higher in
      hospital mortality rate was observed in patients with serum calcium <9.6 and
      >=10.1 mg/dL. Also, 38% and 33% of patients with admission serum calcium <7.9 and
      >=10.1 mg/dL were on calcium supplements before admission, respectively. After
      adjusting for potential confounders, both serum calcium <8.4 and >=10.1 mg/dL
      were associated with an increased risk of in-hospital mortality with ORs of 2.86
      [95% confidence interval (CI) 1.98-4.17], 1.74 (95% CI 1.21-2.53), and 1.69 (95%
      CI 1.10-2.59) when serum calcium were within <7.9, 7.9 to <8.4, and >=10.1 mg/dL,
      respectively. CONCLUSION: Hypocalcemia and hypercalcemia on admission were
      associated with in-hospital mortality. Highest mortality risk is observed in
      patients with admission hypocalcemia (<7.9 mg/dL). One-third of patients with
      hypercalcemia on admission were on calcium supplements.

PMID- 29381080
TI  - Comparison of the effect of a hyaluronate-trehalose solution to hyaluronate alone
      on Ocular Surface Disease Index in patients with moderate to severe dry eye
      disease.
AB  - OBJECTIVE: To describe a post hoc analysis comparing the effect of a hyaluronic
      acid (HA)-trehalose solution to an established eyedrop solution containing HA
      alone using Ocular Surface Disease Index (OSDI) score <19 as a threshold for
      moderate to severe dry eye disease (DED). METHODS: A phase III, randomized,
      controlled, single-blind, multicenter study was conducted in France and Tunisia
      to evaluate the efficacy and safety of HA-trehalose (N = 52) and HA (N = 53)
      administered for 84 days. Eligible patients had moderate to severe DED with OSDI
      >=18. Here the results of a post hoc analysis of the percentage of patients with
      OSDI <19 on Day 35 and Day 84 are reported. RESULTS: Significantly more patients
      had OSDI <19 at Day 84 in the HA-trehalose group than in the HA group (78.8%
      versus 58.5%; p = .025). At Day 35, more patients had OSDI <19 in the HA
      trehalose group than in the HA group, but this difference was not statistically
      significant. Furthermore, approximately twice as many patients in the HA group
      (41.5%) still had OSDI 19-100 at Day 84 compared to the HA-trehalose group
      (21.2%). CONCLUSIONS: This data supports the addition of trehalose to HA
      containing eyedrop solutions to provide better symptomatic relief from moderate
      to severe DED, based on an OSDI score of <19 after 84 days of treatment.

PMID- 29381082
TI  - Mediation effect of depressive symptoms in the relationship between perceived
      control and wellbeing in patients with heart failure and their partners.
AB  - BACKGROUND: As treatment has improved, patients with heart failure live longer,
      and the care mostly takes place at home with partners providing the main
      assistance. Perceived control over heart failure is important in managing self
      care activities to maintain health in patients and their family. Depressive
      symptoms are associated with impaired health status in patients with heart
      failure and their family. However, there is limited knowledge about how
      depressive symptoms affect the relationship between health status and perceived
      control over heart failure in patients with heart failure and their cohabiting
      partners. AIM: The aim of this study was to examine whether the relationship
      between perceived control and health status (i.e. mental and physical) was
      mediated by depressive symptoms in patients with heart failure and their
      partners. METHODS: In this secondary data analysis, we included 132 heart failure
      patients and 132 partners who completed measures of depressive symptoms (the Beck
      depression inventory II), perceived control (the control attitude scale), and
      physical and mental health status (the short form-36) instruments. The mediation
      effect of depression was examined using a series of multiple regression in
      patients and their family caregivers separately. RESULTS: We found a mediator
      effect of depressive symptoms in the relationship between perceived control and
      mental health status in both patients and partners. The relationship between
      perceived control and physical health status was mediated by depressive symptoms
      in the patients, not in the partners. CONCLUSION: Efforts to improve self-care
      management and maintenance by targeting perceived control may be more effective
      if depressive symptoms are also effectively managed.

PMID- 29381081
TI  - Epigenetic mechanisms in the placenta related to infant neurodevelopment.
AB  - As the 'third brain' the placenta links the developing fetal brain and the
      maternal brain enabling study of epigenetic process in placental genes that
      affect infant neurodevelopment. We described the characteristics and findings of
      the 17 studies on epigenetic processes in placental genes and human infant
      neurobehavior. Studies showed consistent findings in the same cohort of term
      healthy infants across epigenetic processes (DNA methylation, genome wide, gene
      and miRNA expression) genomic region (single and multiple genes, imprinted genes
      and miRNAs) using candidate gene and genome wide approaches and across
      biobehavioral systems (neurobehavior, cry acoustics and neuroendocrine). Despite
      limitations, studies support future work on molecular processes in placental
      genes related to neurodevelopmental trajectories including implications for
      intervention.

PMID- 29381083
TI  - Optimizing Data Reduction Procedures in Spatial Heterodyne Raman Spectroscopy
      with Applications to Planetary Surface Analogs.
AB  - A spatial heterodyne Raman spectrometer (SHRS) is a variant of a Michelson
      interferometer in which the mirrors of a Michelson are replaced with two
      stationary diffraction gratings. When light enters the SHRS, it is reflected off
      of diffraction gratings at frequency-dependent angles that produce crossed
      wavefronts in space that can be imaged using a plane array detector. The crossed
      wavefronts, which represent a superposition of interference fringes, are
      converted to a Raman spectrum upon applying a Fourier transform. In this work, a
      new approach to intensity calibration is discussed that originates from modeling
      the shot noise produced by the SHRS and converting the real noise to idealized
      white noise as predicted by theory. This procedure has two effects. First, the
      technique produces Raman spectra with white noise. Second, when the mean of the
      noise is normalized to one, the technique produces Raman spectra where the
      intensity axis is equivalent to signal-to-noise ratio. The data reduction
      technique is then applied to the measurement of materials of interest to the
      planetary science community, including minerals and inorganic salts, at a
      distance of 5 m from the collecting optic.

PMID- 29381084
TI  - Characterization of SCCA-IgM as a biomarker of liver disease in an Asian cohort
      of patients.
AB  - Viral hepatitis infection is a major global issue and a leading cause of liver
      disease and associated deaths. Over time, patients infected with hepatitis B
      (HBV) or C virus (HCV) develop cirrhosis and, eventually, hepatocellular
      carcinoma (HCC). For this reason, they need to be constantly monitored. Current
      Asian guidelines recommend the determination of serum alpha-fetoprotein (AFP)
      together with liver ultrasounds every six months to detect HCC nodules. However,
      both methods have several limitations, and other biomarkers have been studied for
      monitoring cirrhosis, including SCCA-IgM, an immune-complex formed by Squamous
      Cell Carcinoma Antigen and IgM. To date, SCCA-IgM has been validated as a novel
      biomarker for liver diseases only in European populations. The aim of our study
      was to analyze SCCA-IgM as a biomarker to monitor cirrhosis evolution in an Asian
      cohort of patients and to compare its performance to that of AFP. We analyzed the
      concentration of AFP and SCCA-IgM in serum samples obtained from a group of Asian
      adult patients with cirrhosis or HCC and a control group of patients admitted for
      gastrointestinal disorders. In untreated patients and similarly to AFP, SCCA-IgM
      levels were significantly higher in patients with cirrhosis compared to those
      with HCC. In addition, SCCA-IgM, but not AFP serological levels, were
      significantly lower in HCC patients who were treated with surgical resection
      compared to those who received a different therapy.

PMID- 29381085
TI  - Gum acacia stabilized silver nanoparticles based nano-cargo for enhanced anti
      arthritic potentials of hesperidin in adjuvant induced arthritic rats.
AB  - Nanomedicines anticipate drug delivery to inflamed tissues in rheumatoid
      arthritis (RA) with greater efficacy and lesser side effects. This study
      investigates the anti-arthritic potentials of Hesperidin (HP) loaded in gum
      acacia (GA) stabilized green silver nanoparticles (AgNPs). Synthesized GA-AgNPs
      were characterized through UV-vis spectrophotometer, zetasizer and atomic force
      microscope (AFM). The HP and its loaded NPs were tested for RA in Complete
      Freund's adjuvant (CFA) induced arthritis model. GA-AgNPs were found in nano
      range size with negative charge, spherical shape and loaded increased HP amount.
      HP loaded GA-AgNPs showed minimal arthritic score exhibiting mild to moderate
      tissue swelling, reduced degenerative changes along with mild articular changes.
      Histopathological analysis revealed comparatively lesser influx of inflammatory
      cells and diminished granulamatous inflammation in ankle joints tissues in the
      presence of HP loaded GA-AgNPs. RT-PCR revealed that HP loaded GA-AgNPs
      significantly reduced the TLRs mRNA expression. Results validate GA stabilized
      green AgNPs as stable nano-cargos for targeted delivery of HP for restoring the
      progression of RA.

PMID- 29381086
TI  - Treatment of vaginal atrophy with estriol and lactobacilli combination: a
      clinical review.
AB  - In recent years, a vast quantity of clinical data has been accumulated on the
      pathophysiology of symptomatic vulvovaginal atrophy (VVA)/genitourinary syndrome
      of menopause (GSM) in peri- and postmenopausal women and on the treatment options
      for these conditions. Guidelines from several societies have recently been
      updated in favor of VVA/GSM vaginal therapy with the lowest possible doses of
      estrogens. The combination of a vaginal ultra-low dose of 0.03 mg of estriol (E3)
      and lyophilized, viable Lactobacillus acidophilus KS400 (0.03 mg-E3/L) is a
      unique product with a dual mechanism of action supporting not only the
      proliferation and maturation of the vaginal epithelium, but also restoration of
      the lactobacillary microflora. It has been demonstrated efficiently to establish
      and maintain a healthy vaginal ecosystem. Use of this combination considerably
      improves the clinical signs and symptoms as well as the quality of life of
      menopausal women suffering from vaginal atrophy. This combination therapy is well
      tolerated with a low overall incidence of side-effects and negligible estriol
      absorption. Based on recent scientific evidence and current treatment guidelines,
      the 0.03 mg-E3/L combination could be considered one of the options for the
      treatment of symptomatic vaginal atrophy in aging menopausal women.

PMID- 29381087
TI  - The evolution of coronary stents.
AB  - INTRODUCTION: Percutaneous coronary intervention (PCI) is 40 years old this year.
      From its humble beginnings of experimental work, PCI has transitioned over years
      with coronary artery stenting now a standard medical procedure performed
      throughout the world. Areas covered: The conversion from plain old balloon
      angioplasty (POBA) to the present era of drug eluting stents (DES) has been
      driven by many technological advances and large bodies of clinical trial
      evidence. The journey to present day practice has seen many setbacks, such as
      acute vessel closure with POBA; rates of instant restenosis with bare metal
      stents (BMS) and more recently, high rates of stent thrombosis with bioabsorbable
      platforms. This work discusses POBA, why there was a need for BMS, the use of
      inhibiting drugs to create 1st generation DES, the change of components to 2nd
      generation DES, the use of absorbable drug reservoirs and platforms, and possible
      future directions with Prohealing Endothelial Progenitor Cell Capture Stents.
      Expert commentary: This paper reviews the evolution from the original pioneering
      work to modern day practice, highlighting landmark trials that changed practice.
      Modern day contemporary practice is now very safe based on the latest drug
      eluting stents and supported by large datasets.

PMID- 29381088
TI  - Low dose monocrotaline causes a selective pulmonary vascular lesion in male and
      female pneumonectomized rats.
AB  - : Purpose/Aim: Low doses (30-80 mg/kg) of monocrotaline are commonly used to
      create experimental models of pulmonary hypertension in rats. At these doses,
      monocrotaline causes pulmonary endothelial apoptosis and acute lung injury which
      ultimately results in pulmonary vascular disease. Higher doses of monocrotaline
      (300 mg/kg) are known to create severe liver injury, but previous investigations
      with lower doses have not reported histology in other organs to determine whether
      the vascular injury with monocrotaline is pulmonary-selective or generalized.
      MATERIALS AND METHODS: We therefore sought to determine whether monocrotaline
      caused extra-pulmonary injury at doses commonly used in pulmonary hypertension
      studies. We performed left pneumonectomy on young male and female rats before
      administering 50-60 mg/kg monocrotaline 7 days later. We monitored serum
      chemistry and urine dipsticks during the first 3 weeks while the animals
      developed pulmonary hypertension. After 3 weeks, we sacrificed animals and
      stained the lungs and highly vascular visceral organs (kidney, liver, and spleen)
      for elastin to evaluate the degree of vascular injury and remodeling. RESULTS: We
      did not observe proteinuria or significant transaminitis over the 3 weeks
      following monocrotaline. As previously published, monocrotaline caused severe
      pulmonary vascular disease with neointimal lesions and medial hypertrophy. We did
      not identify significant large or small arterial damage in the kidneys, liver, or
      spleen. Two external veterinary pathologists did not identify histopathology in
      the kidneys, liver, or spleen of these rats. CONCLUSIONS: We conclude that 50-60
      mg/kg of monocrotaline causes a selective pulmonary vascular lesion and that male
      and female rats have little non-pulmonary damage over 3 weeks at these doses of
      monocrotaline.

PMID- 29381089
TI  - RNA-Seq investigation and in vivo study the effect of strontium ranelate on
      ovariectomized rat via the involvement of ROCK1.
AB  - Strontium ranelate (SrR) is an anti-osteoporosis drug with excellent osteogenic
      and angiogenic capacity. In this study, we aimed to investigate the osteogenesis
      and angiogenesis effects of SrR and the underlying mechanism involved. RNA-Seq
      was conducted to examine the effects of SrR on gene expression in ovariectomy rat
      bone marrow mesenchymal stem cells (OVX-rBMSCs). To validate the different
      expressed gene in vitro, the effects of gene interference and overexpression in
      osteogenic induction environment of OVX-rBMSCs and in primary osteoblasts were
      studied. RNA-Seq showed that ROCK1 significantly increased after SrR treatment in
      OVX-rBMSCs, and further validated by real-time PCR and western blotting.
      Overexpression of ROCK1 promoted osteogenic differentiation of OVX-rBMSCs and
      induced cell viability and inhibited apoptosis of primary osteoblasts, which was
      reversed by inhibition of ROCK1 by RNA interference or ROCK1 inhibitor (Y-27632)
      after SrR treatment. Furthermore, the SrR was loaded on nano-structured
      hydroxyapatite (nano-HAp) particulates to promote osteogenesis and angiogenesis
      in repairing of the femoral condyle bone defect using ovariectomy rat model.
      Taken together, ROCK1 is one of the targets that SrR promotes the osteogenic
      differentiation of OVX-rBMSCs and cell viability of primary osteoblasts, the nano
      HAp particles could act as carriers for SrR to repair bone defects.

PMID- 29381091
TI  - Development of an interprofessional competency framework for collaborative
      practice in Japan.
AB  - Rapid aging of the population necessitates improved collaboration among
      healthcare professionals. Unfortunately, interprofessional collaboration has yet
      to be implemented effectively in Japan. Therefore, we aimed to develop an
      interprofessional competency framework for Japanese healthcare professionals. The
      project was conducted as a four-step process, starting with initial
      categorization of potential competency domains,, followed by guiding principle
      and prototype development, feedback on the prototype, and final consensus. First,
      authors (JH and MO) collected opinions about competency in interprofessional
      collaboration at two academic meetings of the Japan Association for
      Interprofessional Education (JAIPE) and then analyzed the data thematically.
      Second, a project team consisting of JAIPE and University representatives
      extracted the domains and statements as prototype 1. Third, seven representatives
      from professional organizations joined the project team and developed prototype
      2. We then called for feedback on the revised prototype 2 at both an open
      symposium and via public comments. Following revision of prototype 2, a new
      project team including 20 university, professional organization and health
      practitioner representatives finally discussed prototype 3, developed the final
      draft and reached a consensus. In analysis after collecting the data, we
      extracted 11 themes. We developed four key principles which applied to six
      domains as prototype 1-3. Finally, our competency framework included two core
      domains of "Patient-/client-/family-/community-centered" and "Interprofessional
      communication", and four peripheral domains of "Role contribution", "Facilitation
      of relationships", "Reflection" and "Understanding of others". We developed an
      interprofessional competency framework in Japan which consists of two core and
      four peripheral domains. The interprofessional competency framework is likely to
      affect the understanding of "high-context" and "relationalism" in Japanese
      healthcare. We hope that our interprofessional competency framework will
      encourage the systematic implementation of interprofessional education and
      collaboration in Japan.

PMID- 29381090
TI  - A Prospective Multicenter Evaluation of the Accuracy of a Novel Implanted
      Continuous Glucose Sensor: PRECISE II.
AB  - BACKGROUND: Persistent use of real-time continuous glucose monitoring (CGM)
      improves diabetes control in individuals with type 1 diabetes (T1D) and type 2
      diabetes (T2D). METHODS: PRECISE II was a nonrandomized, blinded, prospective,
      single-arm, multicenter study that evaluated the accuracy and safety of the
      implantable Eversense CGM system among adult participants with T1D and T2D
      (NCT02647905). The primary endpoint was the mean absolute relative difference
      (MARD) between paired Eversense and Yellow Springs Instrument (YSI) reference
      measurements through 90 days postinsertion for reference glucose values from 40
      to 400 mg/dL. Additional endpoints included Clarke Error Grid analysis and sensor
      longevity. The primary safety endpoint was the incidence of device-related or
      sensor insertion/removal procedure-related serious adverse events (SAEs) through
      90 days postinsertion. RESULTS: Ninety participants received the CGM system. The
      overall MARD value against reference glucose values was 8.8% (95% confidence
      interval: 8.1%-9.3%), which was significantly lower than the prespecified 20%
      performance goal for accuracy (P < 0.0001). Ninety-three percent of CGM values
      were within 20/20% of reference values over the total glucose range of 40-400
      mg/dL. Clarke Error Grid analysis showed 99.3% of samples in the clinically
      acceptable error zones A (92.8%) and B (6.5%). Ninety-one percent of sensors were
      functional through day 90. One related SAE (1.1%) occurred during the study for
      removal of a sensor. CONCLUSIONS: The PRECISE II trial demonstrated that the
      Eversense CGM system provided accurate glucose readings through the intended 90
      day sensor life with a favorable safety profile.

PMID- 29381092
TI  - Absorption Spectra of Ethanol and Water Using a Photothermal Lens
      Spectrophotometer.
AB  - In this work we report on the absorption spectra of ethanol and water in the
      region 430-700 nm using a homemade halogen lamp-based photothermal lens
      spectrophotometer with a multipass probe-beam configuration. The spectra also
      include well resolved, higher absorption overtones. The instrument achieves high
      sensitivity due to multiple reflections within the optical cavity containing the
      sample. Finally, an Arduino board was used for collecting and digitizing the
      signal, thus enabling a more compact device.

PMID- 29381093
TI  - The Effects of Inflammation on Alpha 1 Antitrypsin Levels in a National Screening
      Cohort.
AB  - Alpha 1 Antitrypsin (AAT) is a highly polymorphic serum protein. Several genetic
      variants are associated with varying degrees of decreased serum levels; however,
      these levels can rise in response to infection, inflammation, injury and estrogen
      levels. Although the effect of inflammation is well established, it has never
      been studied quantitatively with respect to specific genotypes in a large
      representative sample. Using data from a national AAT deficiency-targeted
      screening cohort, we evaluated AAT levels of patients with normal and deficiency
      genotypes in response to inflammation, indicated by elevated serum C-reactive
      protein (CRP). Additionally, we utilized a regression analysis to adjust for the
      effect of inflammation for each genotype. Across all stratified genotype groups,
      increased AAT levels were observed in patients with CRP >=5 mg/L. Different AAT
      phenotypes reacted differently in the acute phase; M showed a strong response and
      Z a reduced reaction. Nevertheless, we discovered that inflammation significantly
      masked clinically relevant base AAT levels in some PI*MZ individuals;
      approximately a quarter of PI*MZ samples showed signs of inflammation. Median AAT
      levels (mg/dL) in the presence of inflammation are given for several genotypes;
      numbers in parentheses are levels from the cohort without inflammation/adjusted
      levels from the cohort with inflammation using the newly devised algorithm:
      PI*MM: 162 (142/140); PI*MS: 136 (117/115); PI*MZ: 104 (85/89); PI*MF: 161
      (132/141); PI*SS: 115 (96/91); PI*SZ: 66 (54/50). We conclude that simultaneous
      determinations of CRP and AAT levels, and genotyping are clinically valuable in
      defining AAT variants and that the effect of inflammation can be adjusted for.

PMID- 29381094
TI  - Erratum.

PMID- 29381095
TI  - In-Vitro Effects of Secreted Frizzled-Related Protein 1 (SFRP1) On Human Corneal
      Epithelial Cells.
AB  - PURPOSE: Limbal corneal epithelial cells (LCECs) are responsible for corneal
      epithelial cell regeneration. However, corneal central epithelial cells (CCECs)
      are also suggested to display potential for self-renewal. Additionally, a better
      understanding of molecules that regulate corneal epithelial cell regeneration is
      important for studying conditions affecting the cornea, for example, keratoconus.
      Given our previous findings of reduced levels of secreted frizzled-related
      protein 1 (SFRP1) in tears from keratoconus patients compared to controls, we
      investigated the effects of SFRP1 on the proliferation and survival of cultured
      central and limbal human corneal epithelial cells. MATERIAL AND METHODS: Limbal
      and central corneal explants were established from postmortem human corneas, and
      cultured in CnT-PR, an epithelial-specific tissue culture media. Subcultured
      cells from explants were immunostained for the cytokeratins CK3, 12, 19, and the
      proliferative/oligopotent markers Ki67 and p63. BrdU flow cytometry, Alamar Blue
      and LDH assays were used to assess effects of SFRP1 treatment on central and
      LCECs. RESULTS: Primary limbal and central corneal epithelial cells were
      successfully cultured in vitro to confluence (P6 and P4, respectively). They all
      expressed varying levels of cytokeratins CK3, CK12 and CK19, and Ki67 and p63.
      Additionally, they showed significantly increased metabolic activity after SFRP1
      treatment (p < 0.05), with a maximum response at 1 MUg/mL of SPRF1. No difference
      in proliferation was detected in SFRP1 treated LCECs; however, a reduction in
      cell death was noted (p < 0.05). CONCLUSION: Similar to the LCECs, primary human
      CCECs can be cultured in vitro, and expressed epithelial markers. SFRP1
      demonstrated an improvement on the metabolic activity of both CCECs and LCECs,
      which in LCECs could be resulted from reduced cell death. This may have
      implications in degenerative corneal disorders, such as keratoconus.

PMID- 29381096
TI  - Influence of menopausal status on the main contributors of muscle quality.
AB  - BACKGROUND: Muscle quality is a strong independent predictor of physical
      function. Body mass and fatness, muscle mass and cardiorespiratory fitness are
      known to influence muscle quality. OBJECTIVE: To identify the contributors of
      muscle quality in young and postmenopausal women and whether hormone replacement
      therapy (HT) could influence this relationship at the age of menopause. METHODS:
      Fifty-four postmenopausal women, 27 not on HT (PMW) and 27 on HT (PMW-HT), and 33
      young women (YW) were evaluated for (1) body composition (body mass index, BMI),
      total fat mass (FM, %), appendicular lean mass (ALM, in kg and %), and
      appendicular skeletal mass index (ASMI = ALM/height2 in kg/m2); (2) absolute peak
      oxygen uptake (VO2peak, in ml/min) and relative peak oxygen uptake (VO2peakRel in
      ml/kg/min); and (3) absolute isometric knee extension strength (iKES in kg) and
      relative isometric knee extension strength (iKES/BMI and iKES/ALM). RESULTS: YW,
      PMW and PMW-HT had similar BMI (32.1 +/- 10.2, 27.3 +/- 4.7 and 26.7 +/- 4 kg/m2)
      and FM (39.8 +/- 10.0, 39.8 +/- 7.3 and 39.9 +/- 7.1%), respectively.
      Correlations were found between iKES/BMI index and FM (r = -0.52), ALM (r = 0.32)
      and VO2peak (r = 0.31). Regression analysis demonstrated that, in YW, total
      amount of variance in iKES/BMI was mostly explained by ALM (42%), whereas, in PMW
      and PMW-HT, it was cumulatively explained by FM along with VO2peakRel (34 and
      46%, respectively). CONCLUSION: The main contributors of muscle quality differ
      between young and postmenopausal women and HT does not seem to influence this
      relationship.

PMID- 29381097
TI  - The relationship between speech recognition, behavioural listening effort, and
      subjective ratings.
AB  - OBJECTIVE: The purpose of this study was to evaluate the reliability and validity
      of four subjective questions related to listening effort. A secondary purpose of
      this study was to evaluate the effects of hearing aid beamforming microphone
      arrays on word recognition and listening effort. DESIGN: Participants answered
      subjective questions immediately following testing in a dual-task paradigm with
      three microphone settings in a moderately reverberant laboratory environment in
      two noise configurations. Participants rated their: (1) mental work, (2) desire
      to improve the situation, (3) tiredness, and (4) desire to give up. Data were
      analysed using repeated measures and reliability analyses. STUDY SAMPLE: Eighteen
      adults with symmetrical sensorineural hearing loss participated. RESULTS:
      Beamforming differentially affected word recognition and listening effort.
      Analysis revealed the same pattern of results for behavioural listening effort
      and subjective ratings of desire to improve the situation. Conversely, ratings of
      work revealed the same pattern of results as word recognition performance.
      Ratings of tiredness and desire to give up were unaffected by hearing aid
      microphone or noise configuration. CONCLUSIONS: Participant ratings of their
      desire to control the listening situation appear to reliable subjective
      indicators of listening effort that align with results from a behavioural measure
      of listening effort.

PMID- 29381098
TI  - Are BTK and PLCG2 mutations necessary and sufficient for ibrutinib resistance in
      chronic lymphocytic leukemia?
AB  - INTRODUCTION: Ibrutinib is the first BTK inhibitor to show efficacy in chronic
      lymphocytic leukemia (CLL) and is also the first BTK inhibitor to which patients
      have developed resistance. Mutations in BTK and PLCG2 are found in ~80% of CLL
      patients with acquired resistance to ibrutinib, but it remains unclear if these
      mutations are merely associated with disease relapse or directly cause it. Areas
      covered: Unique properties of both CLL and ibrutinib that complicate attempts to
      definitively conclude whether BTK/PLCG2 mutations are passengers or drivers of
      ibrutinib-resistant disease are reviewed. Characteristics of mutations that drive
      drug resistance are summarized and whether BTK/PLCG2 mutations possess these is
      discussed. These characteristics include (1) identification in multiple patients
      with acquired resistance, (2) in vitro validation of drug-resistant properties,
      (3) mutual exclusivity with one another, (4) increasing frequency over time on
      drug, and (5) high frequency at the time and site of clinical relapse. Expert
      commentary: While BTK/PLCG2 mutations have characteristics suggesting that they
      can drive ibrutinib resistance, this conclusion remains formally unproven until
      specific inhibition of such mutations is shown to cause regression of ibrutinib
      resistant CLL. Data suggest that alternative mechanisms of resistance do exist in
      some patients.

PMID- 29381100
TI  - Multiwavelength Raman Spectroscopic Analysis of Superficial Iron-Chromium Oxides
      Generated Using Laser Irradiation.
AB  - In order to characterize iron-chromium oxides generated by laser irradiation on
      the surface of stainless steel plates, an ultraviolet-visible (UV-Vis) near
      infrared (NIR) multiwavelength excitation Raman analysis has been performed using
      both austenitic SS304 and ferritic SS430 stainless steel samples. Raman spectra
      were obtained using five different excitation wavelengths from blue (455 nm) to
      NIR (830 nm). These measurements have allowed us to observe and identify four
      Raman bands, among which two have not been previously observed for iron-chromium
      oxides, and characterize the existence of different resonant excitation
      conditions for the different excitation wavelengths. For example, when using 455
      nm as excitation wavelength the band at 485 cm-1 did not show up, although that
      when using 830 nm as excitation wavelength is a clear characteristic band for
      iron-chromium oxide. In addition, the dependence of the spectra profile with the
      excitation wavelength for films and microspheres features was observed. This
      experimental Raman analysis shows the importance of the excitation wavelength for
      the characterization of metallic oxides with different features.

PMID- 29381099
TI  - Quality Evaluation Scores are no more Reliable than Gestalt in Evaluating the
      Quality of Emergency Medicine Blogs: A METRIQ Study.
AB  - : Construct: We investigated the quality of emergency medicine (EM) blogs as
      educational resources. PURPOSE: Online medical education resources such as blogs
      are increasingly used by EM trainees and clinicians. However, quality evaluations
      of these resources using gestalt are unreliable. We investigated the reliability
      of two previously derived quality evaluation instruments for blogs. APPROACH:
      Sixty English-language EM websites that published clinically oriented blog posts
      between January 1 and February 24, 2016, were identified. A random number
      generator selected 10 websites, and the 2 most recent clinically oriented blog
      posts from each site were evaluated using gestalt, the Academic Life in Emergency
      Medicine (ALiEM) Approved Instructional Resources (AIR) score, and the Medical
      Education Translational Resources: Impact and Quality (METRIQ-8) score, by a
      sample of medical students, EM residents, and EM attendings. Each rater evaluated
      all 20 blog posts with gestalt and 15 of the 20 blog posts with the ALiEM AIR and
      METRIQ-8 scores. Pearson's correlations were calculated between the average
      scores for each metric. Single-measure intraclass correlation coefficients (ICCs)
      evaluated the reliability of each instrument. RESULTS: Our study included 121
      medical students, 88 EM residents, and 100 EM attendings who completed ratings.
      The average gestalt rating of each blog post correlated strongly with the average
      scores for ALiEM AIR (r = .94) and METRIQ-8 (r = .91). Single-measure ICCs were
      fair for gestalt (0.37, IQR 0.25-0.56), ALiEM AIR (0.41, IQR 0.29-0.60) and
      METRIQ-8 (0.40, IQR 0.28-0.59). CONCLUSION: The average scores of each blog post
      correlated strongly with gestalt ratings. However, neither ALiEM AIR nor METRIQ-8
      showed higher reliability than gestalt. Improved reliability may be possible
      through rater training and instrument refinement.

PMID- 29381101
TI  - Octreotide-modified liposomes containing daunorubicin and dihydroartemisinin for
      treatment of invasive breast cancer.
AB  - Tumor invasion is considered a major promoter in the initiation of tumor
      metastasis, which is supposed to cause most cancer-related deaths. In the present
      study, octreotide (OCT)-modified daunorubicin plus dihydroartemisinin liposomes
      were developed and characterized. Evaluations were undertaken on breast cancer
      MDA-MB-435S cells and MDA-MB-435S xenografts nude mice. The liposomes were ~100
      nm in size with a narrow polydispersity index. In vitro results showed that the
      OCT-modified daunorubicin plus dihydroartemisinin liposomes could enhance
      cytotoxicity and cellular uptake by OCT-SSTRs (somatostatin receptors)-mediated
      active targeting, block on tumor cell wound healing and migration by
      incorporating dihydroartemisinin. The action mechanism might be related to
      regulations on E-cadherin, alpha5beta1-integrin, TGF-beta1, VEGF and MMP2/9 in
      breast cancer cells. In vivo, the liposomes displayed a prolonged circulating
      time, more accumulation in tumor location, and a robust overall antitumor
      efficacy with no obvious toxicity at the test dose in MDA-MB-435S xenograft mice.
      In conclusion, the OCT-modified daunorubicin plus dihydroartemisinin liposomes
      could prevent breast cancer invasion, hence providing a possible strategy for
      treatment of metastatic breast cancer.

PMID- 29381102
TI  - Transvascular therapy of Hepatocellular Carcinoma (HCC), status and developments.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Only 30
      40% of patients diagnosed with HCC are candidates for curative treatment options.
      The remaining majority of patients undergo local, regional or systemic palliative
      therapies. Transvascular therapy of HCC takes advantage of the fact that
      hypervascularized HCCs receive their main perfusion from the hepatic artery. In
      this context transvascular therapy describes different therapies: bland
      embolization (transarterial embolization, TAE), cTACE (conventional transarterial
      chemoembolization), DEB-TACE (TACE with drug-eluting beads, DEB) and SIRT
      (selective internal radiation therapy, radioembolization). cTACE is the most
      common type of transvascular treatment and represents a combination of the intra
      arterial use of a chemotherapeutic agent and embolization. There is no
      standardized regimen for cTACE. It remains unclear whether the intra-arterial
      application of a chemotherapeutic agent is definitely required, because bland
      embolization alone using very small spherical particles shows tumor necrosis
      comparable to cTACE. For DEB-TACE microparticles loaded with a chemotherapeutic
      drug combine the advantages of cTACE and bland embolization.

PMID- 29381103
TI  - Comparison of automated ribosomal intergenic spacer analysis (ARISA) and
      denaturing gradient gel electrophoresis (DGGE) techniques for analysing the
      influence of diet on ruminal bacterial diversity.
AB  - The objective of this study was to compare the automated ribosomal intergenic
      spacer analysis (ARISA) and the denaturing gradient gel electrophoresis (DGGE)
      techniques for analysing the effects of diet on diversity in bacterial pellets
      isolated from the liquid (liquid-associated bacteria (LAB)) and solid (solid
      associated bacteria (SAB)) phase of the rumen. The four experimental diets
      contained forage to concentrate ratios of 70:30 or 30:70 and had either alfalfa
      hay or grass hay as forage. Four rumen-fistulated animals (two sheep and two
      goats) received the diets in a Latin square design. Bacterial pellets (LAB and
      SAB) were isolated at 2 h post-feeding for DNA extraction and analysed by ARISA
      and DGGE. The number of peaks in individual samples ranged from 48 to 99 for LAB
      and from 41 to 95 for SAB with ARISA, and values of DGGE-bands ranged from 27 to
      50 for LAB and from 18 to 45 for SAB. The LAB samples from high concentrate-fed
      animals tended (p < 0.10) to show greater peak numbers and Shannon index values
      than those isolated from high forage-fed animals with ARISA, but no differences
      were identified with DGGE. The SAB samples from high concentrate-fed animals had
      lower (p < 0.05) peak numbers and Shannon index values than those from animals
      fed high-forage diets with ARISA, but only a trend was noticed for these
      parameters with DGGE (p < 0.10). The ARISA detected that animals fed alfalfa hay
      diets showed lower (p < 0.05) SAB diversity than those fed grass hay diets, but
      no differences were observed with DGGE. No effect of forage type on LAB diversity
      was detected by any technique. In this study, ARISA detected some changes in
      ruminal bacterial communities that were not detected by DGGE, and therefore ARISA
      was considered more appropriate for assessing bacterial diversity of ruminal
      bacterial pellets. The results highlight the impact of the fingerprinting
      technique used to draw conclusions on dietary factors affecting bacterial
      diversity in ruminal bacterial pellets.

PMID- 29381104
TI  - Current issues: patient perception of clinical photography.

PMID- 29381105
TI  - The application of the Mayer multimedia learning theory to medical PowerPoint
      slide show presentations.
AB  - PowerPointTM and other slideware have the potential to be overused and abused.
      Presentations should be tailored using scientifically derived principles in order
      to maximise teaching potential. This paper applies the Mayer Multimedia Learning
      Theory (with its twelve evidence-based principles of multimedia design) to
      medical slide show presentations. The best way to avoid audience boredom or
      mortification is to adhere to these precepts. Presentations stand or fall on the
      quality, relevance, and integrity of the content. Slide shows should supplement a
      presentation, and not substitute for it. The key principles are brevity, cogency
      and clarity.

PMID- 29381106
TI  - Medical evidence and proof of cause of death in Nigerian courts.
AB  - Medical evidence has continued to be given and evaluated in Nigerian courts since
      Nigeria's independence from Britain. The attitudes of the courts have been
      largely varied against a background of the individual judge's appreciation of
      forensic science and who should be considered an expert witness. The prosecution
      and defence lawyers equally display limited knowledge of forensic science. This
      paper reviews some of the decided cases, the reasons for the verdicts, forensic
      concerns and recommendations for the improvement of the criminal justice system.
      There is need to improve the knowledge base of the bar and the bench.

PMID- 29381107
TI  - Retraction notice.
AB  - At the request of the Journal Editor and the Publisher, the following article has
      been retracted. Sajid M.S. Bioethics and Medical Education. Scottish Medical
      Journal 2008; 53(2): 62-63. DOI: 10.1258/rsmsmj.53.2.62 The above paper has
      substantial unreferenced overlap to the following paper: Jafarey A.M. Bioethics
      and Medical Education. Journal of Pakistan Medical Association 2003; 53 (6): 210
      214.

PMID- 29381108
TI  - Food Availability Is the Main Driver of Seasonal Changes in Resting Metabolic
      Rate in African Striped Mice (Rhabdomys pumilio).
AB  - Resting metabolic rate (RMR) influences energy allocation to survival, growth,
      and reproduction, and significant seasonal changes in RMR have been reported.
      According to one hypothesis, seasonal changes in RMR are mainly attributable to
      seasonal changes in ambient temperature (Ta) and food availability. Studies on
      species from the temperate zone indicated that food availability is the main
      driver. However, whether this is generally true is unknown, because studies from
      the tropics and subtropics, where most species live, are rare. We studied the
      African striped mouse (Rhabdomys pumilio) inhabiting a seasonal environment with
      hot dry seasons with low food availability and cold moist seasons with high food
      availability. Using 603 RMR measurements of 277 individuals, we investigated the
      relative importance of food availability and Ta on RMR during selected periods,
      in which one extrinsic factor varied while the other factor was relatively
      constant. At similar Ta, residual RMR increased with increasing levels of food
      availability. In contrast, different Ta did not influence residual RMR at similar
      levels of food availability. Thus, our study on a subtropical species gives
      support to the hypothesis, derived from temperate zone species, that food
      availability mainly drives seasonal changes in RMR.

PMID- 29381109
TI  - Natural Language-based Machine Learning Models for the Annotation of Clinical
      Radiology Reports.
AB  - Purpose To compare different methods for generating features from radiology
      reports and to develop a method to automatically identify findings in these
      reports. Materials and Methods In this study, 96 303 head computed tomography
      (CT) reports were obtained. The linguistic complexity of these reports was
      compared with that of alternative corpora. Head CT reports were preprocessed, and
      machine-analyzable features were constructed by using bag-of-words (BOW), word
      embedding, and Latent Dirichlet allocation-based approaches. Ultimately, 1004
      head CT reports were manually labeled for findings of interest by physicians, and
      a subset of these were deemed critical findings. Lasso logistic regression was
      used to train models for physician-assigned labels on 602 of 1004 head CT reports
      (60%) using the constructed features, and the performance of these models was
      validated on a held-out 402 of 1004 reports (40%). Models were scored by area
      under the receiver operating characteristic curve (AUC), and aggregate AUC
      statistics were reported for (a) all labels, (b) critical labels, and (c) the
      presence of any critical finding in a report. Sensitivity, specificity, accuracy,
      and F1 score were reported for the best performing model's (a) predictions of all
      labels and (b) identification of reports containing critical findings. Results
      The best-performing model (BOW with unigrams, bigrams, and trigrams plus average
      word embeddings vector) had a held-out AUC of 0.966 for identifying the presence
      of any critical head CT finding and an average 0.957 AUC across all head CT
      findings. Sensitivity and specificity for identifying the presence of any
      critical finding were 92.59% (175 of 189) and 89.67% (191 of 213), respectively.
      Average sensitivity and specificity across all findings were 90.25% (1898 of
      2103) and 91.72% (18 351 of 20 007), respectively. Simpler BOW methods achieved
      results competitive with those of more sophisticated approaches, with an average
      AUC for presence of any critical finding of 0.951 for unigram BOW versus 0.966
      for the best-performing model. The Yule I of the head CT corpus was 34, markedly
      lower than that of the Reuters corpus (at 103) or I2B2 discharge summaries (at
      271), indicating lower linguistic complexity. Conclusion Automated methods can be
      used to identify findings in radiology reports. The success of this approach
      benefits from the standardized language of these reports. With this method, a
      large labeled corpus can be generated for applications such as deep learning. (c)
      RSNA, 2018 Online supplemental material is available for this article.

PMID- 29381110
TI  - Qualities of Sore Throat Index (QuaSTI): measuring descriptors of sore throat in
      a randomized, placebo-controlled trial.
AB  - AIM: Patients with pharyngitis often describe various sensory, affective and
      evaluative pain qualities. Using an 11-word/phrase index, the Qualities of Sore
      Throat Index (QuaSTI), we characterized throat symptoms and evaluated changes in
      a randomized controlled trial (NCT01986361). MATERIALS & METHODS: Patients
      received a single flurbiprofen 8.75 mg (n = 101) or placebo (n = 21) lozenge and
      rated throat soreness at baseline and regular intervals over 3 h, and the QuaSTI
      at baseline, 1, 2 and 3 h post-treatment. RESULTS: The QuaSTI distinguished
      active drug from placebo and detected clinically important (>=2-point) changes
      over 3 h. Mean change from baseline over 3 h was significantly greater for
      flurbiprofen (154%) than placebo (p < 0.05). CONCLUSION: The QuaSTI is a
      sensitive instrument for measuring therapeutic effects in patients with
      pharyngitis.

PMID- 29381111
TI  - Neighborhood Poverty and 9-1-1 Ambulance Response Time.
AB  - BACKGROUND: Are 9-1-1 ambulances relatively late to poorer neighborhoods? Studies
      suggesting so often rely on weak measures of neighborhood (e.g., postal zip
      code), limit the analysis to particular ambulance encounters (e.g., cardiac
      arrest responses), and do little to account for variations in dispatch priority
      or intervention severity. METHODS: We merged EMS ambulance contact records in a
      single California county (n = 87,554) with tract-level data from the American
      Community Survey (n = 300). After calculating tract-level median ambulance
      response time (MART), we used ordinary least squares (OLS) regression to estimate
      a conditional average relationship between neighborhood poverty and MART and
      quantile regression to condition this relationship on 25th, 50th, and 75th
      percentiles of MART. We also specified each of these outcomes by five dispatch
      priorities and by three intervention severities. For each model, we estimated the
      associated changes in MART per 10 percentage point increase in tract-level
      poverty while adjusting for emergency department proximity, population density,
      and population size. RESULTS: Our study produced three major findings. First,
      most of our tests suggested tract-level poverty was negatively associated with
      MART. Our baseline OLS model estimates that a 10 percentage point increase in
      tract-level poverty is associated with almost a 24 s decrease in MART (-23.55 s,
      95% confidence interval [CI] -33.13 to -13.98). Results from our quantile
      regression models provided further evidence for this association. Second, we did
      not find evidence that ambulances are relatively late to poorer neighborhoods
      when specifying MART by dispatch priority. Third, we were also unable to identify
      a positive association between tract-level poverty and MART when we specified our
      outcomes by three intervention severities. Across each of our 36 models, tract
      level poverty was either not significantly associated with MART or was negatively
      associated with MART by a magnitude smaller than a full minute per estimated 10
      percentage point increase in poverty concentration. CONCLUSION: Our study
      challenges the commonly held assumption that ambulances are later to poor
      neighborhoods. We scrutinize our findings before cautiously considering their
      relevance for ambulance response time research and for ongoing conversations on
      the relationship between neighborhood poverty and prehospital care.

PMID- 29381112
TI  - Links between social environment and health care utilization and costs.
AB  - The social environment influences health outcomes for older adults and could be
      an important target for interventions to reduce costly medical care. We sought to
      understand which elements of the social environment distinguish communities that
      achieve lower health care utilization and costs from communities that experience
      higher health care utilization and costs for older adults with complex needs. We
      used a sequential explanatory mixed methods approach. We classified community
      performance based on three outcomes: rate of hospitalizations for ambulatory care
      sensitive conditions, all-cause risk-standardized hospital readmission rates, and
      Medicare spending per beneficiary. We conducted in-depth interviews with key
      informants (N = 245) from organizations providing health or social services.
      Higher performing communities were distinguished by several aspects of social
      environment, and these features were lacking in lower performing communities: 1)
      strong informal support networks; 2) partnerships between faith-based
      organizations and health care and social service organizations; and 3) grassroots
      organizing and advocacy efforts. Higher performing communities share similar
      social environmental features that complement the work of health care and social
      service organizations. Many of the supportive features and programs identified in
      the higher performing communities were developed locally and with limited
      governmental funding, providing opportunities for improvement.

PMID- 29381113
TI  - Anxiety is more important than depression in MS - No.

PMID- 29381114
TI  - Synergistic Effects of Continuous Low Level Heat Wraps and Vitamins in Improving
      Balance and Gait in Adults.
AB  - Ageing is associated with a loss of balance and mobility. This study was
      conducted to determine if the use of heat, vitamins alone or heat with vitamins
      could increase mobility and balance in adults with mobility impairments. Eighty
      adults in the age range between 55 and 64 were randomly divided into 4 different
      groups; low level continues heat (LLCH), vitamins (VT) alone, vitamins combined
      with heat (VT + H), and control group. Subjects were sedentary individuals that
      were not participating in any balance or walking exercises regularly and were not
      taking vitamins for at least 1 year. 4000 units vitamin D, 1000 units vitamin E,
      300mg CoQ10, 600 mg Calcium, 1 tablet multivitamin were taken each day in the VT
      and VT + H groups. LLCH was applied with a dry chemical heat wrap, average
      temperature 42 degrees C for 4 hours per day over the upper leg. The outcome was
      assessed through postural sway and tremor during standing, tremor, gait speed,
      symmetry, ground reaction force, and muscle activity during gait. All
      experimental groups showed significant improvement in balance and walking ability
      after 4 months of interventions (p < 0.05) but no significant changes were found
      in the control group. The difference between the control group and all other
      groups was significant (p < 0.05). The greatest improvements were found in VT + H
      group after 4 months. This is evidenced by better balance, less muscle tremor and
      faster and more stable gait, especially with the heat and vitamins used together.
      Heat and vitamins used together were synergistic.

PMID- 29381115
TI  - Anxiety is more important than depression in MS - Yes.

PMID- 29381116
TI  - Alcohol Consumption and Physical Activity in Austrian College Students-A Cross
      Sectional Study.
AB  - BACKGROUND: The age of college students is considered as crucial for developing
      health-related behaviors, e.g., alcohol consumption or a physically active
      lifestyle. Previous research reported a positive relationship between alcohol
      consumption and physical activity (PA) in college students. However, the main
      body of research was done in students from the United States who might differ
      from European students. OBJECTIVES: Thus the aim of this study was to analyze the
      relationship between alcohol consumption and PA in a sample of Austrian college
      students. METHODS: In a cross-sectional design, 861 Austrian students from
      various study fields responded to a web-based questionnaire. Self-reported
      alcohol consumption, PA, and relevant sociodemographic variables were assessed.
      Multiple regression analyses were used to study the relationship between alcohol
      consumption and PA. RESULTS: In none of the regression models, a significant
      relationship between alcohol consumption and PA was found. There was a
      significant influence of sex, age, relationship status, education level, and
      study field on alcohol consumption. Male, older, and undergraduate students
      studying social sciences without a relationship reported higher alcohol
      consumption. Conclusions/Importance: The results do not support a general
      relationship between alcohol consumption and PA among urban Austrian college
      students of various study fields. Compared to other variables (e.g., sex,
      relationship status), PA seems to be less important in relation to the
      consumption of alcohol. This study challenges a global perspective on a positive
      relationship between alcohol consumption and PA and highlights the need for more
      cross-cultural investigations.

PMID- 29381117
TI  - Exploring women's decisions about childbearing after the lifting of the one-child
      policy.
AB  - In 2016, China officially ended the 'one-child' policy permitting all couples to
      have two children for the first time since 1979. While the policy was relaxed due
      to demographic concerns, it simultaneously provided many women with a new
      reproductive opportunity. The goal of this study was to qualitatively understand
      the childbearing decision process in the new era of the two-child policy. We
      conducted in-depth, semi-structured interviews with 45 postpartum women at two
      hospitals in Zhejiang Province, China. The interviews explored women's views on
      the two-child policy and reproductive decisions and how they decided to have
      their first or second child. Most women approved of the lifting of the one-child
      policy; however, many were hesitant or uncertain about their own decisions to
      have second children. Many felt pressured to have two children for the good of,
      or as an obligation to, the family. However, they also felt that caring for two
      children was burdensome, and that they would have to sacrifice a lot in terms of
      freedom, energy and money. Their responses to the new reproductive opportunity
      highlight the complexity of childbearing decision-making in modern Chinese
      society, against a background of persisting traditional values.

PMID- 29381118
TI  - Social workers can help older adults prepare for and respond to natural and man
      made emergencies.

PMID- 29381119
TI  - Access to Showers and Change Rooms at Work Associated With Active Commuting Among
      Older Workers: Findings From a National Population Survey.
AB  - Access to workplace showers and change rooms (WS/CR) has been found to be
      associated with active commuting (AC). Yet it is unclear whether this extends to
      older workers. We examined the association between WS/CR and AC (walking,
      cycling) comparing older and younger workers. Data came from 53,294 respondents
      to the 2007-2008 Canadian Community Health Survey. Associations between WS/CR and
      walking and cycling were analyzed for main effects and by age and sex using
      logistic regression. Compared with younger ages, workers 50 to 75 years old were
      more likely to cycle to work if WS/CR were available (odds ratio [OR] = 1.71, 95%
      confidence interval [CI] = [1.13, 2.58]), though the overall and sex-related
      associations between WS/CR and AC were nonsignificant. WS/CR may be a promising
      strategy to promote AC particularly among older workers. With large numbers of
      middle- and older-aged adults working longer, the implications of AC for
      sustaining good health may be considerable.

PMID- 29381120
TI  - Reduced Swimming Performance Repeatedly Evolves on Loss of Migration in
      Landlocked Populations of Alewife.
AB  - Whole-organism performance tasks are accomplished by the integration of
      morphological traits and physiological functions. Understanding how evolutionary
      change in morphology and physiology influences whole-organism performance will
      yield insight into the factors that shape its own evolution. We demonstrate that
      nonmigratory populations of alewife (Alosa pseudoharengus) have evolved reduced
      swimming performance in parallel, compared with their migratory ancestor. In
      contrast to theoretically and empirically based predictions, poor swimming among
      nonmigratory populations is unrelated to the evolution of osmoregulation and
      occurs despite the fact that nonmigratory alewives have a more fusiform (torpedo
      like) body shape than their ancestor. Our results suggest that elimination of
      long-distance migration from the life cycle has shaped performance more than
      changes in body shape and physiological regulatory capacity.

PMID- 29381122
TI  - Irinotecan/IR-820 coloaded nanocomposite as a cooperative nanoplatform for
      combinational therapy of tumor.
AB  - AIM: To enhance synergistic therapeutic effects in breast cancer therapy. Here,
      we used hollow mesoporous silica nanoparticles as a biocompatible carrier to
      coload chemotherapy drugs Irinotecan and near-infrared IR-820 dye, which enhanced
      antitumor efficacy by combining chemotherapy and phototherapy. METHODS: The
      successful synthesis of hollow mesoporous silica nanoparticles/Irinotecan/IR820
      (HMII) nanocomplex was confirmed by Fourier  transform infrared spectroscopy and
      Fluorescence spectra. The photothermal conversion efficiency and antitumor
      efficiency in murine breast cancer cells (EMT-6) bearing mice were further
      evaluated. RESULTS: The results demonstrated that HMII enhanced the delivery of
      Irinotecan and IR-820 into EMT-6 cells. HMII generated a high temperature upon a
      near-infrared laser irradiation (808 nm), and showed higher therapeutic efficacy
      in EMT-6-bearing mice compared with either HMII without laser or free drug with a
      laser. CONCLUSION: HMII is a desired drug codelivery system to efficiently
      inhibit the growth of breast cancer.

PMID- 29381123
TI  - Anxiety is more important than depression in MS - Commentary.

PMID- 29381124
TI  - The computational study of the gamma-Fe2O3 nanoparticle as Carmustine drug
      delivery system: DFT approach.
AB  - In the present study, it is attempted to scrutinize the properties of the
      maghemite nanoparticle as a Carmustine drug delivery system by means of the
      density functional theory calculations regarding their geometries, adsorption
      energies, vibrational frequencies, and topological features of the electron
      density. Based on the density functional theory results, it is found that the
      interaction between Carmustine drug molecule and maghemite nanoparticle is weak;
      so that, the adsorption of the Carmustine drug is typically physisorption. It is
      also found that the intermolecular hydrogen bonds between the drug and the
      nanoparticle play the significant role in the stability of the physisorption
      configurations. The nature of the intermolecular interactions has been explored
      by calculation of the electron densities and their Laplacian at the bond critical
      points using Atoms-in-Molecule theory. Moreover, natural bond orbital analysis
      indicates that the Carmustine molecule can be adsorbed on the nanoparticle
      surface with a charge transfer from the Carmustine drug to the nanoparticle.

PMID- 29381125
TI  - Talking about sex in pregnancy: reflections from the field in urban South Africa.
AB  - Qualitative research with close engagement in the field allows researchers and
      participants to build relationships and establish trust, enabling researchers to
      collect meaningful and sensitive information. Drawing on findings from a study
      conducted in an urban setting in South Africa, we discuss the challenges faced
      when interviewing pregnant women with HIV infection, retaining them in the study,
      and extending the study to include their partners. We discuss the dynamics of
      pregnancy and draw lessons from interviews concerned with personal, sensitive
      issues. The study on which we draw was conducted in Johannesburg, South Africa,
      and was nested in a larger prospective cohort study of women and their infants,
      which in turn was part of a case control study. Sensitive topics are difficult
      and complex, but to ignore these and stay in safe territory is to ignore some of
      the most pressing questions of our time. It is important that those who conduct
      interviews are well trained and able to engage empathetically with participants,
      and that some form of counselling is available for both participants and
      researchers.

PMID- 29381126
TI  - The evolving management of small bowel adenocarcinoma.
AB  - BACKGROUND: Small bowel adenocarcinoma (SBA) is rare despite the fact that the
      small bowel represents the longest part and has the largest surface of all
      alimentary tract sections. Its incidence is 50-fold lower than that of colorectal
      carcinoma. It is often diagnosed at an advanced stage due to atypical and late
      symptoms, its low index of suspicion, difficult endoscopic access and poor
      detection by radiological imaging, resulting in impaired outcome. Due to its
      rarity and being molecularly a unique intestinal cancer, data regarding its
      optimal management are relatively sparse. MATERIAL AND METHODS: A PubMed search
      was performed to identify relevant manuscripts that were recently published.
      Emerging data regarding the pathogenesis, the diagnosis and the treatment of SBA
      that resulted from recent research are discussed in this comprehensive review.
      RESULTS: Genomic analysis has demonstrated that SBA is a molecularly unique
      intestinal cancer. Double balloon enteroscopy and capsule endoscopy are novel
      techniques which may result in earlier diagnosis and consequently in improvement
      of the generally poor prognosis. For clinically localized disease, the quality of
      surgery has recently been defined, with removal of at least 8-10 lymph nodes
      correlating with improved prognosis. Moreover, adjuvant chemotherapy seems to
      improve outcome of stage III disease. The combination of a fluoropyrimidine and
      oxaliplatin appears to be the most effective systemic chemotherapy for
      disseminated disease. Genomic profiling can identify potentially targetable
      genomic alterations in a significant proportion of SBA patients. The role of
      administration of targeted agents or immune checkpoint inhibitors is still
      unknown and subject of ongoing clinical trials. In the common case of peritoneal
      metastases, recent studies have shown that cytoreductive surgery and
      intraoperative hyperthermic intraperitoneal chemotherapy may be an attractive
      treatment option in selected patients. CONCLUSIONS: SBA is a rare and unique
      malignancy, whose diagnostic approach and treatment are evolving, resulting in
      improved outcome.

PMID- 29381127
TI  - Does restructuring theory and clinical courses better prepare nursing students to
      manage residents with challenging behaviors in long-term care settings?
AB  - Bachelor of Nursing students (BN) placed in long-term care encounter residents
      who exhibit challenging behaviors. Students are often inadequately prepared to
      manage these behaviors, and this is a source of distress for students. This study
      explored whether enhancing and restructuring theoretical and clinical courses
      resulted in student nurses feeling better prepared to manage residents'
      challenging behaviors and improve their levels of distress. This study was
      conducted in two phases with 116 BN students (first phase) and 99 students
      (second phase) where the course on older adults was restructured. The findings of
      this study indicated that students who felt less prepared experienced greater
      distress by residents' behaviors than those who felt better prepared. Scheduling
      a theoretical course on the care of older adults prior to the clinical course
      placement, as well as offering an online learning module focused on responsive
      behaviors, significantly increased students' feelings of preparedness to manage
      residents' complex behaviors.

PMID- 29381128
TI  - Supporting ethical use of electronic monitoring for people living with dementia:
      Social work's role in assessment, decision-making, and review.
AB  - Walking outdoors supports health and well-being, but some people living with
      dementia are at increased risk of getting lost and of harm while missing.
      Electronic monitoring can potentially play an important preventative role by
      enabling the person's location to be continuously monitored by caregivers.
      However, there are considerable ethical concerns arising from electronic
      monitoring. This paper explores these thematically, drawing attention to its
      implications for autonomy and liberty; privacy; dignity; the rights and needs of
      caregivers and families; beneficence and nonmaleficence. Following from this, key
      questions for consideration in social work assessment are identified. The ethical
      issues necessitate assessment of the person's unique circumstances and
      preferences and that of their caregivers, and careful ethical deliberation in
      decision-making. Social work can play an important role in facilitating inclusive
      assessment and decision-making, leading to consensus on intervening with
      electronic monitoring. The need for the ongoing review following implementation
      is discussed to track whether decisions need modification in light of the
      experience of usage. In conclusion, while legislative instruments and
      professional codes of ethics frame social work practice responses, there is need
      for a nuanced debate about ethical use of electronic monitoring and specific
      guidance to inform assessment, decision-making, and review.

PMID- 29381129
TI  - Are existing standard methods suitable for the evaluation of nanomedicines: some
      case studies.
AB  - The use of nanotechnology in medical products has been demonstrated at laboratory
      scale, and many resulting nanomedicines are in the translational phase toward
      clinical applications, with global market trends indicating strong growth of the
      sector in the coming years. The translation of nanomedicines toward the clinic
      and subsequent commercialization may require the development of new or adaptation
      of existing standards to ensure the quality, safety and efficacy of such
      products. This work addresses some identified needs, and illustrates the
      shortcomings of currently used standardized methods when applied to medical
      nanoparticles to assess particle size, drug loading, drug release and in vitro
      safety. Alternative physicochemical, and in vitro toxicology methods, with the
      potential to qualify as future standards supporting the evaluation of
      nanomedicine are provided.

PMID- 29381130
TI  - Feedback control of microbubble cavitation for ultrasound-mediated blood-brain
      barrier disruption in non-human primates under magnetic resonance guidance.
AB  - Focused ultrasound (FUS) in combination with microbubbles is capable of
      noninvasive, site-targeted delivery of drugs through the blood-brain barrier
      (BBB). Although acoustic parameters are reproducible in small animals, their
      control remains challenging in primates due to skull heterogeneity. This study
      describes a 7-T magnetic resonance (MR)-guided FUS system designed for BBB
      disruption in non-human primates (NHP) with a robust feedback control based on
      passive cavitation detection (PCD). Contrast enhanced T1-weighted MR images
      confirmed the BBB opening in NHP sonicated during 2 min with 500-kHz frequency,
      pulse length of 10 ms, and pulse repetition frequency of 5 Hz. The safe acoustic
      pressure range from 185 +/- 22 kPa to 266 +/- 4 kPa in one representative case
      was estimated from combining data from the acoustic beam profile with the BBB
      opening and hemorrhage profiles obtained from MR images. A maximum amount of MR
      contrast agent at focus was observed at 30 min after sonication with a relative
      contrast enhancement of 67% +/- 15% (in comparison to that found in muscles). The
      feedback control based on PCD using relative spectra was shown to be robust,
      allowing comparisons across animals and experimental sessions. Finally, we also
      demonstrated that PCD can test acoustic coupling conditions, which improves the
      efficacy and safety of ultrasound transmission into the brain.

PMID- 29381132
TI  - Writhing.

PMID- 29381131
TI  - Systematic Reviews Published in the Cochrane Library April-May 2017.
AB  - The Cochrane Library of Systematic Reviews is published monthly online (
      http://www.thecochranelibrary.com ). The library currently contains 7332 complete
      reviews and 2520 protocols for reviews in production. In addition, there are
      citations of 1,055,253 randomized controlled trials and 15,764 cited papers in
      the Cochrane Methodology Register. The Health Technology Assessment database
      contains some 17,000 citations. The impact factor of the Cochrane Library stands
      at 6.1. This report attempted to identify all relevant reviews published in the 2
      months to May 31, 2017. Eight reviews have been identified that have potential
      relevance for practitioners in pain and palliative medicine. Readers are
      encouraged to access the full report for any articles of interest, as only a
      brief commentary is provided.

PMID- 29381133
TI  - Gabapentin for Cough in Cancer.
AB  - Cough is a common problem among cancer patients, especially lung cancer patients.
      Gabapentin has been shown to be effective in reducing cough number and severity
      in patients with idiopathic refractory cough. The authors report here the
      successful use of gabapentin at usual doses to treat cough in cancer patients,
      including two with lung cancer, with minimal side effects. Gabapentin may be a
      useful addition to the symptom management toolbox for palliation of cancer
      symptoms.

PMID- 29381134
TI  - Novel Highly Pathogenic Avian Influenza A(H5N6) Virus in the Netherlands,
      December 2017.
AB  - A novel highly pathogenic avian influenza A(H5N6) virus affecting wild birds and
      commercial poultry was detected in the Netherlands in December 2017. Phylogenetic
      analysis demonstrated that the virus is a reassortant of H5N8 clade 2.3.4.4
      viruses and not related to the Asian H5N6 viruses that caused human infections.

PMID- 29381135
TI  - NADPH oxidase mediates microtubule alterations and diaphragm dysfunction in
      dystrophic mice.
AB  - Skeletal muscle from mdx mice is characterized by increased Nox2 ROS, altered
      microtubule network, increased muscle stiffness, and decreased muscle/respiratory
      function. While microtubule de-tyrosination has been suggested to increase
      stiffness and Nox2 ROS production in isolated single myofibers, its role in
      altering tissue stiffness and muscle function has not been established. Because
      Nox2 ROS production is upregulated prior to microtubule network alterations and
      ROS affect microtubule formation, we investigated the role of Nox2 ROS in
      diaphragm tissue microtubule organization, stiffness and muscle/respiratory
      function. Eliminating Nox2 ROS prevents microtubule disorganization and reduces
      fibrosis and muscle stiffness in mdx diaphragm. Fibrosis accounts for the
      majority of variance in diaphragm stiffness and decreased function, implicating
      altered extracellular matrix and not microtubule de-tyrosination as a modulator
      of diaphragm tissue function. Ultimately, inhibiting Nox2 ROS production
      increased force and respiratory function in dystrophic diaphragm, establishing
      Nox2 as a potential therapeutic target in Duchenne muscular dystrophy.

PMID- 29381136
TI  - COX16 promotes COX2 metallation and assembly during respiratory complex IV
      biogenesis.
AB  - Cytochrome c oxidase of the mitochondrial oxidative phosphorylation system
      reduces molecular oxygen with redox equivalent-derived electrons. The conserved
      mitochondrial-encoded COX1- and COX2-subunits are the heme- and copper-center
      containing core subunits that catalyze water formation. COX1 and COX2 initially
      follow independent biogenesis pathways creating assembly modules with subunit
      specific, chaperone-like assembly factors that assist in redox centers formation.
      Here, we find that COX16, a protein required for cytochrome c oxidase assembly,
      interacts specifically with newly synthesized COX2 and its copper center-forming
      metallochaperones SCO1, SCO2, and COA6. The recruitment of SCO1 to the COX2
      module is COX16- dependent and patient-mimicking mutations in SCO1 affect
      interaction with COX16. These findings implicate COX16 in CuA-site formation.
      Surprisingly, COX16 is also found in COX1-containing assembly intermediates and
      COX2 recruitment to COX1. We conclude that COX16 participates in merging the COX1
      and COX2 assembly lines.

PMID- 29381137
TI  - Multivesicular bodies mediate long-range retrograde NGF-TrkA signaling.
AB  - The development of neurons in the peripheral nervous system is dependent on
      target-derived, long-range retrograde neurotrophic factor signals. The prevailing
      view is that target-derived nerve growth factor (NGF), the prototypical
      neurotrophin, and its receptor TrkA are carried retrogradely by early endosomes,
      which serve as TrkA signaling platforms in cell bodies. Here, we report that the
      majority of retrograde TrkA signaling endosomes in mouse sympathetic neurons are
      ultrastructurally and molecularly defined multivesicular bodies (MVBs). In
      contrast to MVBs that carry non-TrkA cargoes from distal axons to cell bodies,
      retrogradely transported TrkA+ MVBs that arrive in cell bodies evade lysosomal
      fusion and instead evolve into TrkA+ single-membrane vesicles that are signaling
      competent. Moreover, TrkA kinase activity associated with retrogradely
      transported TrkA+ MVBs determines TrkA+ endosome evolution and fate. Thus, MVBs
      deliver long-range retrograde NGF signals and serve as signaling and sorting
      platforms in the cell soma, and MVB cargoes dictate their vesicular fate.

PMID- 29381139
TI  - Dietary intake of advanced glycation endproducts is associated with higher levels
      of advanced glycation endproducts in plasma and urine: The CODAM study.
AB  - BACKGROUND & AIMS: Advanced glycation endproducts (AGEs) are formed by the
      reaction between reducing sugars and proteins. AGEs in the body have been
      associated with several age-related diseases. High-heat treated and most
      processed foods are rich in AGEs. The aim of our study was to investigate whether
      dietary AGEs, are associated with plasma and urinary AGE levels. METHODS: In 450
      participants of the Cohort on Diabetes and Atherosclerosis Maastricht study
      (CODAM study) we measured plasma and urine concentrations of the AGEs Nepsilon
      (carboxymethyl)lysine (CML), Nepsilon-(1-carboxyethyl)lysine (CEL) and Ndelta-(5
      hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) using UPLC-MS/MS. We also
      estimated dietary intake of CML, CEL and MG-H1 with the use of a dietary AGE
      database and a food frequency questionnaire (FFQ). We used linear regression to
      investigate the association between standardized dietary AGE intake and
      standardized plasma or urinary AGE levels, after adjustment for age, sex, glucose
      metabolism status, waist circumference, kidney function, energy- and macro
      nutrient intake, smoking status, physical activity, alcohol intake, LDL
      cholesterol and markers of oxidative stress. RESULTS: We found that higher intake
      of dietary CML, CEL and MG-H1 was associated with significantly higher levels of
      free plasma and urinary CML, CEL and MG-H1 (betaCML = 0.253 (95% CI 0.086;
      0.415), betaCEL = 0.194 (95% CI 0.040; 0.339), betaMG-H1 = 0.223 (95% CI 0.069;
      0.373) for plasma and betaCML = 0.223 (95% CI 0.049; 0.393), betaCEL = 0.180 (95%
      CI 0.019; 0.332), betaMG-H1 = 0.196 (95% CI 0.037; 0.349) for urine,
      respectively). In addition, we observed non-significant associations of dietary
      AGEs with their corresponding protein bound plasma AGEs. CONCLUSION: We
      demonstrate that higher intake of dietary AGEs is associated with higher levels
      of AGEs in plasma and urine. Our findings may have important implications for
      those who ingest a diet rich in AGEs.

PMID- 29381140
TI  - Quasiparticle Scattering in Type-II Weyl semimetal MoTe<sub>2</sub>.
AB  - The electronic structure of type-II Weyl semimetal molybdenum ditelluride
      (MoTe<sub>2</sub>) is studied by using scanning tunneling microscopy and density
      functional theory calculations. Through measuring energy-dependent quasiparticle
      interference (QPI) patterns with a cryogenic scanning tunneling microscope,
      several characteristic features are found in the QPI patterns. Two of them arise
      from the Weyl semimetal nature; one is the topological Fermi arc surface state
      and the other can be assigned to be a Weyl point. The remaining structures are
      derived from the scatterings relevant to the bulk electronic states. The findings
      lead to thorough understanding of the topological electronic structure of type-II
      Weyl semimetal MoTe<sub>2</sub>.

PMID- 29381138
TI  - Unique molecular events during reprogramming of human somatic cells to induced
      pluripotent stem cells (iPSCs) at naive state.
AB  - Derivation of human naive cells in the ground state of pluripotency provides
      promising avenues for developmental biology studies and therapeutic
      manipulations. However, the molecular mechanisms involved in the establishment
      and maintenance of human naive pluripotency remain poorly understood. Using the
      human inducible reprogramming system together with the 5iLAF naive induction
      strategy, integrative analysis of transcriptional and epigenetic dynamics across
      the transition from human fibroblasts to naive iPSCs revealed ordered waves of
      gene network activation sharing signatures with those found during embryonic
      development from late embryogenesis to pre-implantation stages. More importantly,
      Transcriptional analysis showed a significant transient reactivation of
      transcripts with 8-cell-stage-like characteristics in the late stage of
      reprogramming, suggesting transient activation of gene network with human zygotic
      genome activation (ZGA)-like signatures during the establishment of naive
      pluripotency. Together, Dissecting the naive reprogramming dynamics by
      integrative analysis improves the understanding of the molecular features
      involved in the generation of naive pluripotency directly from somatic cells.

PMID- 29381141
TI  - Neutral dynamics and cell renewal of colonic crypts in homeostatic regime.
AB  - The self renewal process in colonic crypts is the object of several studies. We
      present here a new compartment model with the following characteristics: (a) we
      distinguish different classes of cells: stem cells, six generations of transit
      amplifying cells and the differentiated cells; (b) in order to take into account
      the monoclonal character of crypts in homeostatic regimes we include symmetric
      divisions of the stem cells. We first consider the dynamic differential equations
      that describe the evolution of the mean values of the populations, but the small
      observed value of the total number of cells involved plus the huge dispersion of
      experimental data found in the literature leads us to study the stochastic
      discrete process. This analysis allows us to study fluctuations, the neutral
      drift that leads to monoclonality, and the effects of the fixation of mutant
      clones.

PMID- 29381142
TI  - Exploring the validity and limitations of the Mott-Gurney law for charge-carrier
      mobility determination of semiconducting thin-films.
AB  - Using drift-diffusion simulations, we investigate the voltage dependence of the
      dark current in single carrier devices typically used to determine charge-carrier
      mobilities. For both low and high voltages, the current increases linearly with
      the applied voltage. Whereas the linear current at low voltages is mainly due to
      space charge in the middle of the device, the linear current at high voltage is
      caused by charge-carrier saturation due to a high degree of injection. As a
      consequence, the current density at these voltages does not follow the classical
      square law derived by Mott and Gurney, and we show that for trap-free devices,
      only for intermediate voltages, a space-charge-limited drift current can be
      observed with a slope that approaches a value of two. We show that, depending on
      the thickness of the semiconductor layer and the size of the injection barriers,
      the two linear current-voltage regimes can dominate the whole voltage range, and
      the intermediate Mott-Gurney regime can shrink or disappear. In this case, which
      will especially occur for thicknesses and injection barriers typical of single
      carrier devices used to probe organic semiconductors, a meaningful analysis using
      the Mott-Gurney law will become unachievable, because a square-law fit can no
      longer be achieved, resulting in the mobility being substantially underestimated.
      General criteria for when to expect deviations from the Mott-Gurney law when used
      for analysis of intrinsic semiconductors are discussed.

PMID- 29381143
TI  - Self-organised fractional quantisation in a hole quantum wire.
AB  - We have investigated hole transport in quantum wires formed by electrostatic
      confinement in strained germanium two-dimensional layers. The ballistic
      conductance characteristics show the regular staircase of quantum levels with
      plateaux at n2e 2/h, where n is an integer, e is the fundamental unit of charge
      and h is Planck's constant. However as the carrier concentration is reduced, the
      quantised levels show a behaviour that is indicative of the formation of a zig
      zag structure and new quantised plateaux appear at low temperatures. In units of
      2e 2/h the new quantised levels correspond to values of n  =  1/4 reducing to 1/8
      in the presence of a strong parallel magnetic field which lifts the spin
      degeneracy but does not quantise the wavefunction. A further plateau is observed
      corresponding to n  =  1/32 which does not change in the presence of a parallel
      magnetic field. These values indicate that the system is behaving as if charge
      was fractionalised with values e/2 and e/4, possible mechanisms are discussed.

PMID- 29381144
TI  - Bismuth oxide film: a promising room-temperature quantum spin Hall insulator.
AB  - Two-dimensional (2D) bismuth films have attracted extensive attention due to
      their nontrivial band topology and tunable electronic properties for achieving
      dissipationless transport devices. The experimental observation of quantum
      transport properties, however, are rather challenging, limiting their potential
      application in nanodevices. Here, we predict, based on first-principles
      calculations, an alternative 2D bismuth oxide, BiO, as an excellent topological
      insulator (TI), whose intrinsic bulk gap reaches up to 0.28 eV. Its nontrivial
      topology is confirmed by topological invariant Z 2 and time-reversal symmetry
      protected helical edge states. The appearance of topological phase is robust
      against mechanical strain and different levels of oxygen coverage in BiO. Since
      the BiO is naturally stable against surface oxidization and degradation, these
      results enrich the topological materials and present an alternative way to design
      topotronics devices at room temperature.

PMID- 29381145
TI  - A dataset of 200 structured product labels annotated for adverse drug reactions.
AB  - Adverse drug reactions (ADRs), unintended and sometimes dangerous effects that a
      drug may have, are one of the leading causes of morbidity and mortality during
      medical care. To date, there is no structured machine-readable authoritative
      source of known ADRs. The United States Food and Drug Administration (FDA)
      partnered with the National Library of Medicine to create a pilot dataset
      containing standardised information about known adverse reactions for 200 FDA
      approved drugs. The Structured Product Labels (SPLs), the documents FDA uses to
      exchange information about drugs and other products, were manually annotated for
      adverse reactions at the mention level to facilitate development and evaluation
      of text mining tools for extraction of ADRs from all SPLs. The ADRs were then
      normalised to the Unified Medical Language System (UMLS) and to the Medical
      Dictionary for Regulatory Activities (MedDRA). We present the curation process
      and the structure of the publicly available database SPL-ADR-200db containing
      5,098 distinct ADRs. The database is available at
      https://bionlp.nlm.nih.gov/tac2017adversereactions/; the code for preparing and
      validating the data is available at https://github.com/lhncbc/fda-ars.

PMID- 29381146
TI  - Australia's continental-scale acoustic tracking database and its automated
      quality control process.
AB  - Our ability to predict species responses to environmental changes relies on
      accurate records of animal movement patterns. Continental-scale acoustic
      telemetry networks are increasingly being established worldwide, producing large
      volumes of information-rich geospatial data. During the last decade, the
      Integrated Marine Observing System's Animal Tracking Facility (IMOS ATF)
      established a permanent array of acoustic receivers around Australia.
      Simultaneously, IMOS developed a centralised national database to foster
      collaborative research across the user community and quantify individual
      behaviour across a broad range of taxa. Here we present the database and quality
      control procedures developed to collate 49.6 million valid detections from 1891
      receiving stations. This dataset consists of detections for 3,777 tags deployed
      on 117 marine species, with distances travelled ranging from a few to thousands
      of kilometres. Connectivity between regions was only made possible by the joint
      contribution of IMOS infrastructure and researcher-funded receivers. This dataset
      constitutes a valuable resource facilitating meta-analysis of animal movement,
      distributions, and habitat use, and is important for relating species
      distribution shifts with environmental covariates.

PMID- 29381147
TI  - Habitual coffee consumption and changes in measures of adiposity: a comprehensive
      study of longitudinal associations.
AB  - BACKGROUND: A relationship between change in coffee consumption and reduced long
      term weight gain has been suggested, but current evidence is inconsistent.
      OBJECTIVE: To examine longitudinal associations between coffee consumption and
      changes in body mass index (BMI), fat mass index (FMI), fat-free mass index
      (FFMI), body fat percentage (BF %) and waist circumference (WC). DESIGN: The
      study consisted of 2128 participants from the Danish part of the MONICA
      (Monitoring Trends and Determinants in Cardiovascular Disease) cohort with
      repeated information on coffee consumption, adiposity measures and covariates
      during an 11-year period. Linear regression analyses were conducted to assess the
      associations between baseline coffee consumption and subsequent change in
      adiposity measures. The same analyses were conducted analyzing associations
      between change in coffee consumption and concurrent as well as subsequent changes
      in adiposity measures. RESULTS: We found no consistent evidence of associations
      between baseline coffee consumption and subsequent 6-year changes in adiposity
      measures. A statistically significant association between increased coffee
      consumption over a 6-year period and decreased concurrent gain in BMI, FMI, BF %
      and WC (-0.05 kg m-2 (95% confidence interval (CI): -0.07, -0.02), -0.04 kg m-2
      (95% CI: -0.06, -0.02), -0.08% (95% CI: -0.13, -0.04) and -0.23 cm (95% CI: 
      0.34, -0.12), respectively, per 1 cup day-1 increase in coffee consumption) was
      found. No association was seen between change in coffee consumption and
      concurrent change in FFMI. Moreover, an initial change in coffee consumption
      during the first 5-year period was not associated with change in adiposity during
      the subsequent 6-year period. CONCLUSIONS: Increased coffee consumption was
      associated with a decreased concurrent gain in body weight, fat mass and waist
      circumference, but the associations were weak. Moreover, a causal relationship
      could not be established, as we found no evidence of associations between an
      initial change in coffee consumption and subsequent change in adiposity.

PMID- 29381149
TI  - Meet some code-breakers of noncoding RNAs.

PMID- 29381150
TI  - Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC)
      predicts risk of disease recurrence after treatment discontinuation in CML.
AB  - This corrects the article DOI: 10.1038/leu.2017.9.

PMID- 29381151
TI  - Deoxygenation of sulphoxides to sulphides with trichlorophosphane.
AB  - An efficient route to deoxygenation of sulphoxides to sulphides with PCl3 under
      mild reaction condition was developed. PCl3 was used as a reducing agent for the
      first time to convert sulphoxides to sulphides. The mild conditions, use of cheap
      and readily available reagent, and broad substrate scope render it a useful
      strategy for preparing sulphides.

PMID- 29381153
TI  - 2017 Reviewers.

PMID- 29381152
TI  - Get Ready, Get Set, Write: Reprise.

PMID- 29381154
TI  - Pursuing Improvement in Clinical Reasoning: The Integrated Clinical Education
      Theory.
AB  - BACKGROUND: The link between clinical education and development of clinical
      reasoning is not well supported by one theoretical perspective. Learning to
      reason during clinical education may be best achieved in a supportive
      sociocultural context of nursing practice that maximizes reasoning opportunities
      and facilitates discourse and meaningful feedback. Prelicensure clinical
      education seldom incorporates these critical components and thus may fail to
      directly promote clinical reasoning skill. METHOD: Theoretical frameworks
      supporting the development of clinical reasoning during clinical education were
      evaluated. Analysis of strengths and gaps in each framework's support of clinical
      reasoning development was conducted. Commensurability of philosophical
      underpinnings was confirmed, and complex relationships among key concepts were
      elucidated. RESULTS: Six key concepts and three tenets comprise an explanatory
      predictive theory-the integrated clinical education theory (ICET). CONCLUSION:
      ICET provides critical theoretical support for inquiry and action to promote
      clinical education that improves development of clinical reasoning skill. [J Nurs
      Educ. 2018;57(1):7-13.].

PMID- 29381155
TI  - Effectiveness of Video-Assisted Debriefing in Health Education: An Integrative
      Review.
AB  - BACKGROUND: Debriefing is an integral component of the high-fidelity simulation
      experience in health education. Video-assisted debriefing (VAD) is used to
      structure debriefing following simulation. This review synthesizes the best
      available evidence about VAD compared with verbal debriefing; moreover, it
      reviews the effectiveness of VAD on students' learning outcomes and learners'
      perceptions of using VAD postsimulation sessions. METHOD: Databases included Med
      line, Scopus, CINAHL, and EMBASE, and articles published between 2000 and 2016
      were reviewed if they used the keywords video-assisted debriefing, HFS,
      debriefing and learning outcomes, and video-playback debriefing. Fourteen studies
      met the inclusion criteria. RESULTS: Three themes emerged: VAD Effectiveness
      Compared to Verbal (Oral) Debriefing, VAD Effectiveness on Learning Outcomes, and
      Learners' Perceptions of VAD Experience. CONCLUSION: VAD following simulation
      experiences compared with other debriefing modalities resulted in mixed findings
      related to learning outcomes in health education. More research on debriefing
      practices is needed that describes all key debriefing components. [J Nurs Educ.
      2018;57(1):14-20.].

PMID- 29381148
TI  - Trans-ethnic analysis of metabochip data identifies two new loci associated with
      BMI.
AB  - OBJECTIVE: Body mass index (BMI) is commonly used to assess obesity, which is
      associated with numerous diseases and negative health outcomes. BMI has been
      shown to be a heritable, polygenic trait, with close to 100 loci previously
      identified and replicated in multiple populations. We aim to replicate known BMI
      loci and identify novel associations in a trans-ethnic study population.
      SUBJECTS: Using eligible participants from the Population Architecture using
      Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis
      of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans
      and European Americans. Participants were genotyped on over 200 000 SNPs on the
      Illumina Metabochip custom array, or imputed into the 1000 Genomes Project (Phase
      I). Linear regression of the natural log of BMI, adjusting for age, sex, study
      site (if applicable), and ancestry principal components, was conducted for each
      race/ethnicity within each study cohort. Race/ethnicity-specific, and combined
      meta-analyses used fixed-effects models. RESULTS: We replicated 15 of 21 BMI loci
      included on the Metabochip, and identified two novel BMI loci at 1q41 (rs2820436)
      and 2q31.1 (rs10930502) at the Metabochip-wide significance threshold (P<2.5 * 10
      7). Bioinformatic functional investigation of SNPs at these loci suggests a
      possible impact on pathways that regulate metabolism and adipose tissue.
      CONCLUSION: Conducting studies in genetically diverse populations continues to be
      a valuable strategy for replicating known loci and uncovering novel BMI
      associations.

PMID- 29381156
TI  - Korean Nursing Students' Acquisition of Evidence-Based Practice and Critical
      Thinking Skills.
AB  - BACKGROUND: Evidence-based practice (EBP) is essential for enhancing nurses'
      quality of care. We identified Korean nursing students' practices, attitudes, and
      knowledge concerning EBP, as well as their critical thinking disposition (CTD).
      METHOD: The EBP Questionnaire (EBPQ) was administered to a convenience sample of
      266 nursing students recruited from four nursing schools in Seoul and its
      metropolitan area. RESULTS: Average EBPQ and CTD total scores were 4.69 +/- 0.64
      and 3.56 +/- 0.32, respectively. Students who were ages ?23 years, male, and
      satisfied with their major demonstrated higher EBPQ and CTD scores. EBPQ scores
      were significantly correlated with CTD scores (r = .459, p < .01), and CTD was an
      explanatory factor of EBP (adjusted R2 = 0.200). CONCLUSION: It is necessary to
      develop comprehensive teaching strategies to help nursing students improve their
      CTD and information utilization skills, as well as integrate EBP in undergraduate
      programs to enhance nurses' EBP abilities. [J Nurs Educ. 2018;57(1):21-27.].

PMID- 29381157
TI  - Burnout and Its Contributing Factors Among Midlevel Academic Nurse Leaders.
AB  - BACKGROUND: Amid concerns regarding administrator shortages, a survey conducted
      by the American Association of Colleges of Nursing indicates that 10% of all
      vacant faculty positions are those that include administrative responsibilities.
      This study was designed to determine the frequency, predictors, and potential
      retention consequences of burnout among midlevel academic nurse leaders, such as
      assistant deans, associate deans, and others. METHOD: The sample consisted of 146
      midlevel academic nurse leaders from 29 schools of nursing. Burnout was measured
      by the emotional exhaustion subscale of the Maslach Burnout Inventory. Logistic
      regression models were estimated to determine effects of study variables on
      burnout and intent to leave. RESULTS: Dissatisfaction with workload,
      dissatisfaction with work-life balance, and hours typically worked per week
      increased odds of burnout. Burnout was associated with intent to leave.
      CONCLUSION: High workloads and long work weeks are increasing the odds of burnout
      among midlevel academic nurse leaders. [J Nurs Educ. 2018;57(1):28-34.].

PMID- 29381158
TI  - Knowledge, Attitudes, and Experience With Advance Directives Among Prelicensure
      Nursing Students.
AB  - BACKGROUND: End-of-life decision making can be distressing for nursing students,
      and the purpose of this investigation was to assess undergraduate nursing
      students' knowledge, attitudes, and experiences with advance directives. METHOD:
      One hundred sixty-six Bachelor of Science in Nursing students at four different
      program levels were surveyed about their knowledge, personal and professional
      experience, and personal and professional attitudes regarding advance directives.
      RESULTS: There was a statistically significant progression of knowledge from the
      junior 1 to the senior 2 semesters. In addition, there was a statistically
      significant difference in personal attitudes about advance directives by
      progressive semesters, in personal and professional attitudes between
      White/Caucasian and Black/African American students, and in knowledge of advance
      directives and professional attitudes between students 18 to 25 years old and
      those 26 years and older. CONCLUSION: It is important that nursing students are
      exposed to advance directives in the prelicensure curriculum to prepare them for
      their role as professional nurses. [J Nurs Educ. 2018;57(1):35-39.].

PMID- 29381159
TI  - Factors Influencing the Development of Cultural Competence in Undergraduate
      Nursing Students.
AB  - BACKGROUND: The study purposes were to assess the cultural competence level and
      to identify factors that influence the development of cultural competence in
      undergraduate nursing students. METHOD: This quantitative study using a
      comparative and predictive design was conducted to recruit 106 undergraduate
      nursing students from a university by sending e-mails to all randomly selected
      Associate in Science in Nursing and RN-to-Bachelor of Science in Nursing students
      for participation. Each student participated voluntarily to self-administer a
      demographic survey and the Inventory for Assessing the Process of Cultural
      Competence among Healthcare Professionals-Student Version (IAPCC-SV(c)). RESULTS:
      The summated score of 20 questions of the IAPCC-SV among the participating
      students was 61.70, indicating a culturally competent level. Approximately 51% of
      the variation in the cultural competence level could be attributed to the
      predictor of cultural encounters. The second strongest predictor was the cultural
      knowledge. CONCLUSION: Further research should focus on identifying cost
      effective teaching and learning strategies using the concept of cultural
      encounters and cultural knowledge to increase students' exposures to individuals
      from other cultures. [J Nurs Educ. 2018;57(1):40-43.].

PMID- 29381160
TI  - Evaluation of a Clinical Policy Learning Activity.
AB  - BACKGROUND: Student groups compare evidence-based practice (EBP) to actual
      practice defined by hospital policies in their clinical rotation sites. This
      article describes a pilot study evaluating this clinical learning activity.
      METHOD: Student and faculty surveys were developed and piloted. Purposive
      sampling with the surveys produced qualitative data and basic statistics to
      evaluate the learning activity. RESULTS: This study suggests that students'
      satisfaction with the clinical learning activity was generally positive. Three
      themes emerged, including Relevance to Clinical Practice, Course Outcomes Met,
      and Reinforcement of Evidence-Based Practice. Faculty surveys showed this
      learning activity was a useful tool for students to learn and utilize EBP.
      CONCLUSION: The learning activity is an effective learning and teaching strategy.
      Collaboration among nursing students, faculty, librarian, and nurses enhanced
      students' understanding of evidence related to policies in nursing practice and
      create a meaningful experience. Further work will focus on validation of the
      surveys. [J Nurs Educ. 2018;57(1):44-48.].

PMID- 29381161
TI  - Examining Admission Factors Predicting Success in a Doctor of Nursing Practice
      Program.
AB  - BACKGROUND: Graduate nursing programs are challenged to select students who are
      likely to succeed and who add to nursing workforce diversity. METHOD: For this
      retrospective study, researchers examined 5 years of admission and retention data
      from a 4-year Bachelor-to-Doctor of Nursing Practice (DNP) program (n=144) at a
      large public midwestern university. Using a multinomial logistic regression
      analysis, four factors were examined to determine which predicted student
      success, delayed success, or failure: last 60-credit grade point average (GPA),
      admission essay score, average recommendation letter score, and demographic data
      (i.e., race, age, gender). RESULTS: GPA, age, and race were found to be
      significant predictors of student outcomes in this program. Writing and
      recommendation scores and gender did not predict student outcomes. CONCLUSION:
      DNP admission committees should consider the weight given to the GPA in their
      admission formulas and be prepared to work with retention committees to support
      older and minority students. [J Nurs Educ. 2018;57(1):49-52.].

PMID- 29381162
TI  - Leadership Development Through Peer-Facilitated Simulation in Nursing Education.
AB  - BACKGROUND: Baccalaureate nursing graduates must possess leadership skills, yet
      few opportunities exist to cultivate leadership abilities in a clinical
      environment. Peer-facilitated learning may increase the leadership skills of
      competence, self-confidence, self-reflection, and role modeling. Facilitating
      human patient simulation provides opportunities to develop leadership skills.
      METHOD: With faculty supervision, senior baccalaureate students led small-group
      simulation experiences with sophomore and junior peers and then conducted
      subsequent debriefings. Quantitative and qualitative descriptive data allowed
      evaluation of students' satisfaction with this teaching innovation and whether
      the experience affected students' desire to take on leadership roles. RESULTS:
      Students expressed satisfaction with the peer-facilitated simulation experience
      and confidence in mastering the content while developing necessary skills for
      practice. CONCLUSION: Peer-facilitated simulation provides an opportunity for
      leadership development and learning. Study results can inform the development of
      nursing curricula to best develop the leadership skills of nursing students. [J
      Nurs Educ. 2018;57(1):53-57.].

PMID- 29381163
TI  - A Comprehensive Approach to Undergraduate Nursing Students' Research Experiences.
AB  - BACKGROUND: As the demands for high-quality nursing care increase and
      organizations are held accountable for patient outcomes, health care must be
      driven by research and evidence-based practice (EBP). Historically, prelicensure
      nursing students have expressed little interest in these topics as they focus on
      establishing the clinical skills necessary to provide care and have found that
      courses on nursing research are not clinically relevant. METHOD: This article
      presents one institution's approach to undergraduate nursing research education
      by three initiatives: (a) a summer research program, (b) a distinguished major
      program, and (c) an EBP approach in the undergraduate nursing research course.
      RESULTS: The results of these initiatives have demonstrated positive outcomes in
      three areas: practice improvements, knowledge dissemination, and student interest
      in research and further professional development. CONCLUSION: These programs have
      proven to be clinically beneficial, while increasing student interest in research
      and further nursing education. [J Nurs Educ. 2018;57(1):58-62.].

PMID- 29381164
TI  - Innovative Learning Activity: Toy Closet: A Growth and Development Game for
      Nursing Students.

PMID- 29381165
TI  - Licensure and Professional Certification Renewal Requirements: 2017 Survey
      Results.

PMID- 29381166
TI  - Identifying the Underlying Educational Needs That Contribute to the Professional
      Practice Gap.
AB  - This article addresses how nursing professional development practitioners and
      nurse planners can meet the educational design process criterion 2 in the
      American Nurses Credentialing Center Primary Accreditation process that also
      corresponds with the Association for Nursing Professional Development's Scope and
      Standards of Practice. J Contin Educ Nurs. 2018;49(2):52-54.

PMID- 29381167
TI  - Re-KALC for a Meaningful Beginning: The Practice of Being.
AB  - The new year is a time for goal setting, reflection, and new beginnings. Often,
      resolutions begin with self-improvements of the physical kind-losing weight,
      exercising, eating clean. These are important ideas and goals, although often
      difficult to sustain in part because sustaining is an implied element of each.
      Intentions are different than goals in the sense that an intention can be
      implemented in any moment in time simply through the process of mindful
      reflection. J Contin Educ Nurs. 2018;49(2):55-56.

PMID- 29381168
TI  - Five-Canon Feedback: Triaging Errors in Writing With Classical Rhetoric.
AB  - Nurse educators may be asked to provide feedback on writing, encountering the
      challenge of determining which errors to address, when, and how. This Teaching
      Tips article, drawing on the author's experience in writing instruction,
      summarizes a novel framework for error triage: the five canons of classical
      rhetoric as described by the Roman rhetorician Quintilian. J Contin Nurs Educ.
      2018;49(2):57-59.

PMID- 29381169
TI  - Empowering Nurses to Lead Interprofessional Collaborative Practice Environments
      Through a Nurse Leadership Institute.
AB  - A year-long Nurse Leadership Institute (NLI) for emerging leaders in primary care
      clinics and acute care environments was developed, implemented, and evaluated.
      The NLI's goal was to foster empowerment in interprofessional collaborative
      practice environments for nurses in the three cohorts of NLIs. The NLI was framed
      around the Five Leadership Practices of modeling the way, inspiring a shared
      vision, challenging the process, enabling others to act, and encouraging the
      heart. To create a professional learning environment, foster community, and
      enhance leadership skills, the Lean In Circle materials developed by Sandberg
      were adapted for content reorganization and discussion. Minimal literature exists
      specifically addressing nursing leadership professionals' development based on
      Sandberg's Circle materials. The findings of the three NLI cohorts reported in
      this article begin to fill this existing knowledge gap. Participants reported a
      significant increase in leadership skills. Recommendations for refinement of
      future NLI offerings are provided. J Contin Educ Nurs. 2018;49(2):61-71.

PMID- 29381170
TI  - Health Literacy: Essential for a Culture of Health.
AB  - BACKGROUND: A culture of health requires a commitment from all-individuals,
      families, communities, organizations, and municipalities-to value health and make
      decisions reflective of a healthy society. At the individual level, health
      literacy is a necessary precursor to assist individuals in achieving a higher
      level of health. METHOD: One method for ensuring that staff members are routinely
      assessing and promoting health literacy is using competencies and practices
      previously identified for all health professions. RESULTS: Cross-walking these
      competencies with the Health Literacy Tapestry model can be extremely helpful in
      framing assessment, action steps, and outcomes for nurses. CONCLUSION:
      Professional development nurse leaders have the challenge of ensuring that nurses
      are addressing patient health literacy as a fundamental nursing activity in every
      nursing-patient-family interaction. Assuming health literacy deficits as a
      "universal approach" to care is one method of ensuring health literacy needs are
      routinely addressed by staff. J Contin Educ Nurs. 2018;49(2):73-78.

PMID- 29381171
TI  - Pilot Study of Educational Gaming to Improve Adherence to an End-Tidal Carbon
      Dioxide Monitoring Protocol.
AB  - BACKGROUND: End-tidal carbon dioxide (ETCO2) monitoring is an important part of
      patient care. Understanding and interpreting ETCO2 wavelengths can be a
      challenge. This pilot study explored the efficacy of a novel approach to
      educating clinicians on ETCO2 monitoring via game theory. METHOD: A video game
      application for ETCO2 monitoring was developed. Clinicians were encouraged to
      play the game over a 3-month period. Compliance with the ETCO2 protocol was
      compared in a random selection of patients admitted before, during, and after the
      intervention. RESULTS: Thirty-eight clinicians completed the preand posttest,
      with a significant difference in test scores (p = .03). The intervention was
      associated with higher adherence to the ETCO2 protocol before and after the
      intervention (p < .05). CONCLUSION: The availability of new technologies has
      created opportunities to develop new approaches to educate clinicians. This study
      showed that the use of a game improved adherence to the ETCO2 protocol. J Contin
      Educ Nurs. 2018;49(2):79-83.

PMID- 29381172
TI  - Comparisons of Knowledge of Dutch Nursing Students and Hospital Nurses on Aging.
AB  - BACKGROUND: Although there is a growing population of older adults admitted to
      hospitals, the literature demonstrates knowledge deficits of nurses regarding
      older patients. This study investigated knowledge levels of both nursing students
      and RNs about older hospitalized patients in relation to their educational level
      and work experience. METHOD: First- and final-year vocational and bachelor
      nursing students, and associate degree and bachelor degree nurses working in the
      hospital setting with 0 to 5 years, 6 to 15 years, and more than 15 years of
      experience, have completed the Knowledge about Older Patients-Quiz (KOP-Q). The
      KOP-Q has a clearly described theoretical base finding its origin in knowledge
      regarding nursing care for older patients and shows good content and construct
      validity. RESULTS: A substantial proportion of participants in all groups
      demonstrated insufficient knowledge about older patients. A difference in
      knowledge exists among nurses with different educational qualifications, and a
      link between years of experience and higher knowledge levels of nurses is found.
      CONCLUSION: Throughout the nursing career, basic care topics in relation to care
      for older patients should play a key role in basic nursing education programs, as
      well as for continuing education programs provided in hospitals for nurses. J
      Contin Educ Nurs. 2018;49(2):84-90.

PMID- 29381173
TI  - Integrative Review of Interprofessional Simulation in Nursing Practice.
AB  - AIM: The aim of this integrative review was to examine what is known about
      interprofessional (IP) simulation involving practicing nurses. BACKGROUND: The
      use of simulation within health care education and practice has rapidly expanded;
      however, there is a gap in what is known about the benefits of nurses engaging in
      IP simulation. METHOD: Five reviewers conducted a systematic literature search on
      studies of IP simulation among practicing nurses, published between January 1,
      2010, and July 1, 2016. An initial sample of 1,400 articles was found and was
      further narrowed to 18 studies. RESULTS: There is a role for IP simulation in
      enhancing nurses' roles and understanding of the roles of other practitioners.
      However, the diversity of studies and lack of rigor prevents the formation of
      conclusive evidence to support IP simulation in enhancing patient care quality
      and safety. CONCLUSION: Structured simulation research designs using published
      guidelines for best practice implementation are needed. J Contin Educ Nurs.
      2018;49(2):91-96.

PMID- 29381174
TI  - ?

PMID- 29381175
TI  - ?

PMID- 29381176
TI  - Diagnostics of type 1 diabetes must be improved
AB  - Incidence of type 1 diabetes in children and adolescents continues to increase
      but diagnosis is often delayed and keto-acidosis too common. More information is
      needed. General auto-antibody screening can be discussed.

PMID- 29381177
TI  - ?

PMID- 29381178
TI  - ?

PMID- 29381179
TI  - ?

PMID- 29381180
TI  - ?

PMID- 29381181
TI  - ?

PMID- 29381182
TI  - ?
AB  - Puerpural fever still exist. A rare condition that must be kept in mind All 33
      claims to the Swedish National Patient Insurance (LOF) in 2010-2014 related to
      obstetric infections, of which 14 were due to endometritis, were examined. Nine
      women suffered from fulminant infections consistent with classical puerperal
      fever (childbed fever), 2 of which were life-threatening. They occurred
      unexpectedly, mainly after uncomplicated deliveries, and were usually caused by
      Group A streptococci. Five women suffered from endometritis with a mild or
      moderate clinical course. All occurred after early birth-related complications
      and were caused by low-virulent bacteria. In order for an infection to occur in a
      healthy woman who undergoes normal delivery, more virulent bacteria appear to be
      required. Since these bacteria may exist in the hospital environment, improved
      hygiene routines are a prerequisite for reducing the number of nosocomial
      infections.

PMID- 29381183
TI  - ?
AB  - The TARGIT-A (TARGeted Intraoperative radioTherapy) multicentre study of early
      breast cancer compared intraoperative radiotherapy with external radiotherapy.
      While the intraoperative radiotherapy was standardised, the external
      postoperative comparison treatment followed established routines in the
      participating treatment centres resulting in substantial variations in dosages
      and treatment durations. The uncertainties in the interpretation of the study
      results created by the design of the TARGIT-A study constitute substantial
      obstacles to the possible introduction of intraoperative radiotherapy for early
      breast cancer.

PMID- 29381184
TI  - ?
AB  - Low adherence to recommended pre-participation cardiac evaluation of Swedish
      athletes Pre-participation cardiac evaluation of athletes is recommended by
      international organizations like the European Society of Cardiology and the
      American Heart Association, as well as by the Swedish Sports Confederation. The
      purpose of the evaluation is to prevent sudden cardiac death in athletes by early
      identification of individuals at risk. To our knowledge, no previous study has
      been made regarding the implementation of pre-participation cardiac evaluation of
      athletes in Sweden. We performed an electronical survey addressing sports clubs
      in one out of 21 districts in which the Swedish Sports Confederation is
      geographically divided. Only four out of 22 responding clubs with elite athletes
      preformed cardiac evaluation. Lack of knowledge about the recommendations as well
      as how to perform the evaluation were mentioned as reasons not to evaluate the
      athletes. Our results indicate the need for more information about pre
      participation cardiac evaluation of athletes in Sweden.

PMID- 29381185
TI  - ?
AB  - Updated criterias for an asthma/COPD clinic in primary care based on Swedish
      guidelines We here present updated criterias for an asthma/COPD clinic in primary
      care based on Swedish guidelines and an estimate of the time required for its
      tasks. Certified staff should assist in diagnosis and follow-up of asthma/COPD
      patients, provide patient education, provide and follow up written management
      plans, facilitate smoking cessation in patients and parents of children with
      asthma, evaluate symptoms with validated tools (ACT, CAT), and assess and support
      physical activity. To provide such care, 4.8 hours are required for asthma/COPD
      nurses and 1.3 hours for physiotherapists per 1,000 listed patients and week. At
      least 1-2 hours/week are needed for the responsible physician. To ensure high
      competence, asthma/COPD nurses should have >=15 credits, advanced level, and
      physiotherapists >=7.5 credits in asthma/COPD, advanced level. The responsible
      physician should have advanced knowledge in the field.

PMID- 29381186
TI  - Where does O6 -methylguanine DNA methyltransferase promoter methylation
      assessment place temozolomide in the future standards of care for glioblastoma?

PMID- 29381187
TI  - The binding of boronated peptides to low affinity mammalian saccharides.
AB  - A 54-member library of boronated octapeptides, with all but the boronated residue
      being proteinogenic, was tested for affinity to a set of saccharides commonly
      found on the terminus of mammalian glycans. After experimentation with a high
      throughput dye-displacement assay, attention was focused on isothermal titration
      calorimetry as a tool to provide reliable affinity data, including enthalpy and
      entropy of binding. A small number of boronated peptides showed higher affinity
      and significant selectivity for N-acetylneuraminic acid over methyl-alpha-d
      galactopyranoside, methyl-alpha/beta-l-fucopyranoside and N-acetyl-d-glucosamine.
      Thermodynamic data showed that for most of the boronated peptides studied,
      saccharide binding was associated with a significant increase in entropy,
      presumably resulting from the displacement of semiordered water molecules from
      around the sugar and/or peptide.

PMID- 29381188
TI  - Noninvasive diagnostic tools for pelvic congestion syndrome: a systematic review.
AB  - INTRODUCTION: In the work-up of patients with suspected pelvic congestion
      syndrome, venography is currently the gold standard. Yet if non-invasive
      diagnostic tools are found to be accurate, invasive venography might no longer be
      indicated as necessary. MATERIAL AND METHODS: A literature search in Pubmed and
      EMBASE was performed from inception until 6 May 2017. Studies comparing non
      invasive diagnostic tools to a reference standard in the work-up of patients with
      (suspected) pelvic congestion syndrome were included. Relevant data were
      extracted and methodological quality of individual included studies was assessed
      by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool.
      RESULTS: Nine studies matched our inclusion criteria. Six studies compared
      ultrasonography to venography and three studies described a magnetic resonance
      imaging technique. In using transvaginal ultrasonography, the occurrence of a
      vein greater than five mm crossing the uterine body had a specificity of 91% (95%
      CI; 77-98%) and occurrence of pelvic varicoceles a sensitivity and specificity of
      100% (95% CI; 89-100%) and 83-100% (95% CI; 66-93%), respectively. In
      transabdominal ultrasonography, reversed caudal flow in the ovarian vein
      accounted for a sensitivity of 100% (95% CI; 84-100%). Detection of pelvic
      congestion syndrome with magnetic resonance imaging techniques resulted in a
      sensitivity varying from 88 to 100%. CONCLUSIONS: The sensitivity of
      ultrasonography and magnetic resonance imaging seem to be adequate, which
      indicates a role for both tests in an early stage of the diagnostic workup.
      However, due to methodological flaws and diversity in outcome parameters, more
      high standard research is necessary to establish a clear advice for clinical
      practice.

PMID- 29381189
TI  - Combination of ultrasonic decontamination, soft tissue curettage, and submucosal
      air polishing with povidone-iodine application for non-surgical therapy of peri
      implantitis: 12 Month clinical outcomes.
AB  - BACKGROUND: The aim of this study is to evaluate clinical outcomes of a concept
      for non-surgical peri-implantitis combining stepwise mechanical debridement
      measures with adjuvant povidone-iodine application with and without systemic
      antibiotics. METHODS: Forty-five patients with chronic periodontitis and a total
      of 164 screw-typed implants with peri-implantitis were included. Peri-implantitis
      was defined as radiographic bone loss of > 2 mm, probing depth (PD) >=5 mm with
      bleeding on probing (BOP). Stepwise treatment of implants was performed with
      ultrasonic debridement, soft tissue curettage (STC), glycine powder air polishing
      (GPAP), and a repeated submucosal application of povidone-iodine. Teeth with PD >
      4 mm were treated simultaneously according to the same concept except STC. In
      cases with severe periodontitis (n = 24), amoxicillin and metronidazole (AM) were
      prescribed for 7 days. RESULTS: After 12 months, implants treated without AM
      showed significant reductions (P < 0.05) of mean PD (1.4 +/- 0.7 mm), clinical
      attachment level (CAL) (1.3 +/- 0.8 mm), and BOP (33.4% +/- 17.2%). In deep
      pockets (PD > 6 mm) changes of mean PD (2.3 +/- 1.3 mm), CAL (2.0 +/- 1.6 mm),
      and BOP (44.0% +/- 41.7%) were more pronounced. Intake of AM did not
      significantly influence the changes in these parameters. However, the reduction
      of implant sites with PD > 4 mm and BOP was significantly higher in patients with
      AM than in those without AM (31.8% +/- 12.6% versus 20.8% +/- 14.7%; P < 0.05).
      CONCLUSIONS: The combination of ultrasonic debridement, STC, and GPAP with
      adjuvant povidone-iodine led to significant clinical improvements at implants.
      Systemic antibiotics had limited effects on the reduction of persisting implant
      sites with treatment need.

PMID- 29381190
TI  - Inhibition of 5-lipoxygenase attenuates inflammation and BONE resorption in
      lipopolysaccharide-induced periodontal disease.
AB  - BACKGROUND: Arachidonate-5-lipoxygenase (5-LO) activity and increased leukotriene
      B4 (LTB4) production have been implicated in various inflammatory conditions.
      Increased production of leukotrienes has been associated with periodontal
      diseases; however, their relative contribution to tissue destruction is unknown.
      In this study, an orally active specific 5-LO inhibitor is used to assess its
      role in inflammation and bone resorption in a murine model of lipopolysaccharide
      (LPS)-induced periodontal disease. METHODS: Periodontal disease was induced in
      Balb/c mice by direct injections of LPS into the palatal gingival tissues
      adjacent to the maxillary first molars three times per week for 4 weeks. Animals
      were treated with biochemical inhibitor (2 mg/kg/daily) or the same volume of the
      vehicle by oral gavage. Microcomputed tomography analysis was used to assess bone
      resorption. Enzyme immunoassay determined LTB4, and enzyme-linked immunosorbent
      assays quantified tumor necrosis factor (TNF), interleukin (IL)-12, and IL-10 in
      gingival tissues. Histologic sections were used for the morphometric analysis
      (number of neutrophils and mononuclear cells). Osteoclasts were counted in
      tartrate-resistant acid phosphatase-stained sections. RESULTS: Administration of
      5-LO inhibitor effectively reduced production of LTB4 (23.7% decrease) and
      significantly reduced TNF and IL-12 levels in gingival tissues. Moreover,
      reduction of LTB4 levels in gingival tissues was associated with a significant
      decrease in bone resorption and a marked reduction in number of osteoclasts and
      inflammatory cells. CONCLUSION: 5-LO activity plays a relevant role in
      inflammation and bone resorption associated with the LPS model of experimental
      periodontal disease.

PMID- 29381191
TI  - Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients
      with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE.
AB  - BACKGROUND: Inotuzumab ozogamicin (InO) has demonstrated efficacy and
      tolerability in patients aged 18 to 78 years with relapsed/refractory acute
      lymphoblastic leukemia (ALL) in the INO-VATE trial. This subset analysis compared
      the efficacy and safety of InO in younger and older patients. METHODS: Intent-to
      treat analyses of morphologic responses and overall survival (OS) included 326
      randomized patients, and safety assessments included 307 patients receiving 1 or
      more doses of the study treatment. Of the 326 patients, 164 received InO at a
      starting dose of 1.8 mg/m2 /cycle (0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and
      15 of a 21- to 28-day cycle [<=6 cycles]); 60 patients were aged >=55 years, and
      104 were aged <55 years. RESULTS: For older and younger patients, the median
      duration of InO therapy and the types and frequencies of adverse events of any
      grade were generally similar. Although the remission rates, median duration of
      remission (DOR), and progression-free survival were similar with InO for those
      aged <55 years and those aged >=55 years, OS was longer for younger patients
      (median, 8.6 vs 5.6 months; hazard ratio, 0.610). Among patients proceeding to
      hematopoietic stem cell transplantation after InO treatment (28% of older
      patients and 58% of younger patients), the incidence of veno-occlusive disease
      was greater in older patients (41% vs 17%). The study database was not locked at
      the time of this analysis. CONCLUSIONS: InO was tolerable in older patients with
      relapsed/refractory ALL. Although OS was longer for younger patients versus older
      patients, InO demonstrated high response rates with similar DOR in the 2 age
      groups. Cancer 2018;124:1722-32. (c) 2018 American Cancer Society.

PMID- 29381192
TI  - Brainstem auditory abnormality in extremely premature babies and the impact of
      neonatal bronchopulmonary dysplasia.
AB  - INTRODUCTION: Extremely premature babies, particularly those who have neonatal
      bronchopulmonary dysplasia, are at risk of brain damage and neurodevelopmental
      impairment. This study aimed to examine functional status of the brainstem
      auditory pathway in extremely premature babies and assess the impact of
      bronchopulmonary dysplasia on function. MATERIAL AND METHODS: Brainstem auditory
      evoked response was studied at term in babies born at <=27 weeks of gestation
      with or without neonatal bronchopulmonary dysplasia. The normal controls were
      term babies without perinatal problems. RESULTS: Compared with the normal
      controls, the extremely premature babies showed an elevated response threshold,
      increased latencies of waves I, III and particularly V. They also showed
      significantly increased I-V and III-V intervals. The amplitudes of waves I and V
      were moderately reduced. These abnormalities were clearly more significant in
      those with bronchopulmonary dysplasia than those without bronchopulmonary
      dysplasia. A direct comparison between the two groups of extremely premature
      babies revealed that wave V latency, and I-V and particularly III-V intervals
      were significantly longer in the babies with bronchopulmonary dysplasia than
      those without bronchopulmonary dysplasia. CONCLUSIONS: Extremely premature babies
      have functional impairment of the brainstem auditory pathway. The impairment is
      clearly more significant in those with bronchopulmonary dysplasia than those
      without bronchopulmonary dysplasia. Neonatal bronchopulmonary dysplasia and
      associated unfavorable conditions are major contributors to brainstem auditory
      impairment in extremely premature babies.

PMID- 29381201
TI  - Image reconstruction by means of focus series1.

PMID- 29381203
TI  - Obituary.

PMID- 29381193
TI  - Racial disparities in the rate of cardiotoxicity of HER2-targeted therapies among
      women with early breast cancer.
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-targeted therapies
      are highly effective at preventing breast cancer recurrence but are associated
      with cardiotoxicity in some patients, and minimal data are available regarding
      racial disparities in the incidence of this toxicity. The authors conducted a
      retrospective study to analyze the association of black or white race with
      treatment-induced cardiotoxicity and incomplete therapy among patients with HER2
      positive early breast cancer. METHODS: Women with HER2-positive, stage I through
      III breast cancer who initiated (neo)adjuvant HER2-targeted therapy (trastuzumab
      with or without pertuzumab) from January 2005 to March 2015 at the authors'
      institution were eligible. We analyzed differences in the incidence of
      cardiotoxicity (a decline in the left ventricular ejection fraction to <50% AND
      an absolute drop in the left ventricular ejection fraction of >=10% from
      baseline) and incomplete therapy (<52 weeks of HER2-targeted therapy) between
      black and white women in univariate and multivariable analyses. RESULTS: The
      authors identified 59 black patients and 157 white patients who had a median
      follow-up 5.2 years. The median patient age was 53 years and was similar for
      black and white patients. The 1-year cardiotoxicity incidence was 12% overall
      (95% confidence interval [CI], 7%-16%), 24% in black women (95% CI, 12%-34%), and
      7% in white women (95% CI, 3%-11%). Black patients had a significantly greater
      probability of incomplete therapy compared with white patients (odds ratio, 4.61;
      95% CI, 1.70-13.07; P = .002). High correlation was observed between a
      cardiotoxicity event and incomplete therapy (96% concordance). CONCLUSIONS: Black
      patients have a higher rate of cardiotoxicity and resultant incomplete adjuvant
      HER2-targeted therapy than white patients. This patient population may benefit
      from enhanced cardiac surveillance, cardioprotective strategies, and early
      referral to cardiology when appropriate. Cancer 2018;124:1904-11. (c) 2018
      American Cancer Society.

PMID- 29381216
TI  - Integrating data from the Investigational Medicinal Product
      Dossier/investigator's brochure. A new tool for translational integration of
      preclinical effects.

PMID- 29381217
TI  - Zinc treatment of hydroponically grown barley plants causes a reduction in root
      and cell hydraulic conductivity and isoform-dependent decrease in aquaporin gene
      expression.
AB  - The cellular and molecular basis of a reduction in root water uptake in plants
      exposed to heavy metals such as zinc (Zn) is poorly studied. The aim of the
      present study on hydroponically grown barley (Hordeum vulgare) was to test
      whether any reduction in root hydraulic conductivity (Lp) in response to Zn
      treatment is accompanied by a reduction in cell Lp and gene expression level of
      aquaporin (AQP) isoforms. Plants were grown in the presence of 0.25 MUM,
      (control), 0.1 and 1 mM Zn in the root medium and analysed when they were 16-18
      days old. Root and cell Lp was determined through exudation and cell pressure
      probe analyses, respectively, and gene expression of five candidate AQPs was
      analysed [real time quantitative polymerase chain reaction (PCR)]. Zinc
      treatments caused significant reductions (25-83%) in transpiration rate, root and
      shoot fresh weight, surface area and stomatal conductance. Zinc concentrations in
      tissues increased more than 100-fold. Root Lp decreased by 24% (0.1 mM Zn) and
      58% (1 mM Zn), while cell Lp decreased by 45 and 71%, respectively. Gene
      expression of AQPs decreased by 14-80%; decreases were statistically significant
      for HvPIP1;3, HvPIP2;4 and HvPIP2;5. Turgor in root cortex cells was not reduced
      by Zn treatments. It is concluded that reductions in plant water flow in response
      to Zn treatment are facilitated through decreases in root (Lp) and shoot
      (stomata) hydraulics. The decrease in root Lp is facilitated through reductions
      in cell Lp and AQP gene expression and may also reflect increased suberization in
      the endodermis.

PMID- 29381218
TI  - Russulaceae: a new genomic dataset to study ecosystem function and evolutionary
      diversification of ectomycorrhizal fungi with their tree associates.
AB  - The family Russulaceae is considered an iconic lineage of mostly mushroom-forming
      basidiomycetes due to their importance as edible mushrooms in many parts of the
      world, and their ubiquity as ectomycorrhizal symbionts in both temperate and
      tropical forested biomes. Although much research has been focused on this group,
      a comprehensive or cohesive synthesis by which to understand the functional
      diversity of the group has yet to develop. Interest in ectomycorrhizal fungi, of
      which Russulaceae is a key lineage, is prodigious due to the important roles they
      play as plant root mutualists in ecosystem functioning, global carbon
      sequestration, and a potential role in technology development toward
      environmental sustainability. As one of the most species-diverse ectomycorrhizal
      lineages, the Russulaceae has recently been the focus of a dense sampling and
      genome sequencing initiative with the Joint Genome Institute aimed at untangling
      their functional roles and testing whether functional niche specialization exists
      for independent lineages of ectomycorrhizal fungi. Here we present a review of
      important studies on this group to contextualize what we know about its members'
      evolutionary history and ecosystem functions, as well as to generate hypotheses
      establishing the Russulaceae as a valuable experimental system.

PMID- 29381219
TI  - Spatial Epidemiology of Alcohol- and Drug-Related Health Problems Among Northern
      Plains American Indians: Nebraska and South Dakota, 2007 to 2012.
AB  - BACKGROUND: Despite high abstinence rates, American Indians experience elevated
      rates of many alcohol and other drug problems. American Indians also
      predominantly reside in poor and rural areas, which may explain some observed
      health disparities. We investigated whether geographic areas including
      reservations or large American Indian populations exhibited greater incidence of
      alcohol- and drug-related hospitalizations. METHODS: We obtained inpatient
      hospitalization records for 2 Northern Plain states (Nebraska and South Dakota)
      for the years 2007 to 2012. We constructed zip code counts for 10 categories of
      hospitalization with diagnoses or injury causation commonly associated with
      alcohol or drug use. We related these to community sociodemographic
      characteristics using Bayesian Poisson space-time regression models and examined
      associations with and without controls for whether each zip code was located
      within an American Indian reservation. RESULTS: Controlling for other demographic
      and economic characteristics, zip codes with greater percentage of American
      Indians exhibited greater incidence for all 10 substance abuse-related health
      outcomes (9 of 10 well supported); zip code areas within American Indian
      reservations had greater incidence of self-inflicted injury and drug dependence
      and abuse, and reduced incidence of alcohol cirrhosis and prescription opioid
      poisoning. However, the analyses generally demonstrated no well-supported
      differences in incidence associated with local residence percentages of American
      Indian versus African American. CONCLUSIONS: In our analyses, ethnicity or
      heredity alone did not account for alcohol- and drug-related hospitalizations
      among Native populations. Aspects of social, economic, and political dimensions
      of Native lives must be considered in the etiology of alcohol- and drug-related
      problems for rural-dwelling indigenous peoples.

PMID- 29381220
TI  - Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel
      Disease by a Bayesian Dashboard System.
AB  - Despite a robust exposure-response relationship of infliximab in inflammatory
      bowel disease (IBD), attempts to adjust dosing to individually predicted serum
      concentrations of infliximab (SICs) are lacking. Compared with labor-intensive
      conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards
      are easy-to-use programs incorporating complex Bayesian statistics to determine
      individual pharmacokinetics. We evaluated various infliximab detection assays and
      the number of samples needed to precisely forecast individual SICs using a
      Bayesian dashboard. We assessed long-term infliximab retention in patients being
      dosed concordantly versus discordantly with Bayesian dashboard recommendations.
      Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab
      maintenance therapy were analyzed by 3 commercially available assays. Data from
      each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter
      precision and residual variability were assessed. Forecast concentrations from
      both systems were compared with observed concentrations. Infliximab retention was
      assessed by prediction for dose intensification via Bayesian dashboard versus
      real-life practice. Forecast precision of SICs varied between detection assays.
      At least 3 SICs from a reliable assay are needed for an accurate forecast. The
      Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed
      concordantly with Bayesian dashboard recommendations had a significantly longer
      median drug survival than those dosed discordantly (51.5 versus 4.6 months, P <
      .0001). The Bayesian dashboard helps to assess the diagnostic performance of
      infliximab detection assays. Three, not single, SICs provide sufficient
      information for individualized dose adjustment when incorporated into the
      Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with
      longer drug retention of infliximab.

PMID- 29381222
TI  - Therapeutic strategies for congenital myasthenic syndromes.
AB  - To date, more than 25 genes have been implicated in the etiology of the
      congenital myasthenic syndromes (CMS), and an ever-growing phenotypic landscape
      is now encountered in the CMS clinic. Unlike the autoimmune form of myasthenia,
      there is no role for immunomodulatory agents in the treatment of CMS. The present
      day drug repertoire comprises acetylcholinesterase inhibitors (mainly
      pyridostigmine), 3,4-diaminopyridine (3,4-DAP), ephedrine, salbutamol/albuterol,
      open-channel blockers (fluoxetine, quinidine), or a combination of these. These
      are prescribed by the specialist in an off-label manner, as there is no drug
      currently licensed for the treatment of these rare diseases. The effective
      pharmacological agent varies according to the genetic form of CMS, and it is
      important to realize that an agent that provides benefit in one CMS subtype can
      be harmful in another. In addition, the time to treatment response is variable
      and tends to be commensurate with the drug used. Here, we summarize for the
      clinician the therapeutic strategies employed in this ever-evolving disease
      spectrum. We also address the barriers to treatment and discuss the treatment of
      CMS in pregnancy.

PMID- 29381221
TI  - Mechanisms underlying B cell immune dysregulation and autoantibody production in
      MuSK myasthenia gravis.
AB  - Pathogenic autoantibodies to muscle-specific tyrosine kinase (MuSK) can be found
      in patients with myasthenia gravis (MG) who do not have detectable antibodies to
      the acetylcholine receptor. Although the autoantibody-mediated pathology is well
      understood, much remains to be learned about the cellular immunology that
      contributes to autoantibody production. To that end, our laboratory has
      investigated particular components associated with the cellular immunopathology
      of MuSK MG. First, we found that B cell tolerance defects contribute to the
      abnormal development of the naive repertoire, which indicates that dysregulation
      occurs before the production of autoantibodies. Second, both the naive and
      antigen-experienced memory B cell repertoire, which we examined through the
      application of high-throughput adaptive immune receptor repertoire sequencing,
      include abnormalities not found in healthy controls. This highlights a broad
      immune dysregulation. Third, using complementary approaches, including production
      of human monoclonal antibodies, we determined that circulating plasmablasts
      directly contribute to the production of MuSK-specific autoantibodies in patients
      experiencing relapse following B cell depletion therapy. These collective
      findings contribute to defining a mechanistic model that describes MuSK MG
      immunopathogenesis.

PMID- 29381223
TI  - Developing treatment guidelines for myasthenia gravis.
AB  - A task force of the Myasthenia Gravis Foundation of America recently published a
      formal consensus statement intended to be a treatment guide for clinicians caring
      for myasthenia gravis (MG) patients worldwide. Its development was stimulated by
      the fact that there is generally no accepted standard of care for MG, and no one
      treatment is best for all MG patients. Also, there are few randomized trials of
      treatments in current use, and the generalizability of the few trials that have
      been successful may be difficult. Fifteen international experts in MG
      participated in the consensus process, which used a simple consensus to develop
      preliminary definitions and the RAND/UCLA Appropriateness Method to quantify
      agreement on treatment guidance statements for seven topics: symptomatic and
      immunosuppressive treatment, intravenous immunoglobulin and plasma exchange,
      impending and manifest myasthenic crisis, thymectomy, juvenile MG, MG with muscle
      specific tyrosine kinase antibodies, and MG in pregnancy. The executive summary
      of the guidance statement was published with open access to facilitate access by
      patients and healthcare professionals, and the full statement, with extensive
      background information, is available online. The guidance statement is a living
      document that will require updates as new treatments and new information on
      current treatments become available.

PMID- 29381224
TI  - The pathological spectrum and clinical correlation of pigmented purpuric
      dermatosis-A retrospective review of 107 cases.
AB  - BACKGROUND: Various pathological findings have been reported in pigmented
      purpuric dermatosis, but their clinical significance remains unclear. METHODS: We
      retrospectively reviewed demographics, clinical presentations, pathological
      patterns and concurrent systemic diseases among biopsy-confirmed cases of
      pigmented purpuric dermatosis. RESULTS: A total of 107 cases were ascertained.
      Five major pathological patterns were identified: lichenoid (45/107, 42.1%),
      perivascular (40/107, 37.4%), interface (11/107, 10.3%), spongiotic (7/107, 6.5%)
      and granulomatous (4/107, 3.7%). Lymphocytic vasculitis was present in 17
      patients (15.9%), and Langerhans cell microabscess was seen in 4 (3.7%). Nine
      patients had partial features mimicking mycosis fungoides but none were
      confirmed. The lichenoid, perivascular and spongiotic patterns correlated to
      lichen aureus, Schamberg and eczematoid clinical variants, respectively. The
      interface pattern was associated with a higher risk of coincident autoimmune
      diseases (18.2%, P = .0280) and gout (27.3%, P = .0180). CONCLUSIONS: This study
      described the wide pathological spectrum of pigmented purpuric dermatosis among
      Asians. Physicians should be aware about the clinical and pathological variations
      to facilitate diagnosis.

PMID- 29381225
TI  - Use of atropine in four-dimensional hysterosalpingo-contrast sonography: Does it
      suppress pain during infertility examination?
AB  - This study aimed to ascertain if atropine is useful for suppressing the pain
      suffered during four-dimensional hysterosalpingo-contrast sonography (4D-HyCoSy)
      when assessing infertility in women. A total of 252 patients were divided into 2
      groups to receive or not receive atropine (0.5 mg) injection 30 minutes before 4D
      HyCoSy. Pain was evaluated using a numerical rating scale (NRS): during 4D
      HyCoSy; upon 2-dimensional transvaginal sonography; before catheter insertion;
      upon insertion and fixation of the catheter into the uterine cavity; 30 minutes
      after 4D-HyCoSy. According to the degree of patency of Fallopian tubes, the 6
      patterns observed were integrated further into 3 patient groups: all-negative
      (both Fallopian tubes were negative), positive-and-negative (one Fallopian tube
      showed patency and the other showed stenosis or non-patency), and all-positive
      (both Fallopian tubes showed stenosis or non-patency). We compared the NRS scores
      and prevalence of side-effects other than pain between the atropine-injection and
      non-atropine-injection groups within the three groups mentioned above. The NRS
      score showed no significant differences among the groups at any time point (all P
      > .05). The different prevalence of side-effects other than pain was significant
      between the atropine-injection and atropine-non-injection groups (P = .012).
      These data suggest that atropine does not reduce pain in patients during 4D
      HyCoSy. However, atropine may reduce the prevalence of other side-effects during
      4D-HyCoSy, which needs a further, large, prospective, multi-cohort study to
      verify.

PMID- 29381226
TI  - Risk for the development of non-alcoholic fatty liver disease: A prospective
      study.
AB  - BACKGROUND AND AIM: Non-invasive assessment was widely used to identify the risk
      of non-alcoholic fatty liver disease (NAFLD) among individuals with increased
      metabolic risks. This study aimed to investigate the prospective relationship
      between ZJU index and the development of NAFLD in a Chinese population. METHODS:
      A cohort of 6310 initially NAFLD-free participants was enrolled in this
      prospective study. Abdominal ultrasound was used to diagnosis NAFLD. NAFLD
      incidence was calculated among participants with different baseline ZJU index
      quintiles. Cox proportional hazards regression analyses were conducted to
      calculate the risks for incident NAFLD. RESULTS: During 37 705 person-year follow
      ups, 1071 incident NAFLD cases were identified. The baseline ZJU index was linear
      and positively correlated with NAFLD incidence. The incidence was 5.53, 11.75,
      23.77, 43.28, and 85.60 cases per 1000 person-year follow-up for participants
      with baseline ZJU index in quintiles 1-5, respectively. Compared with
      participants with baseline ZJU index in quintile 1, the hazard ratios (95%
      confidence interval) for incident NAFLD were 2.092 (1.458-3.002), 4.094 (2.942
      5.698), 7.095 (5.167-9.742), and 13.191 (9.684-17.968) for participants with
      baseline ZJU index in quintiles 2-5, respectively. Further analysis found that
      the changes of ZJU index during follow-up was also independently associated with
      risk for incident NAFLD. CONCLUSIONS: Baseline ZJU index and absolute ZJU index
      changes independently predicts the risk for incident NAFLD in Chinese population.

PMID- 29381227
TI  - Spectrum and origin of mutations in sporadic cases of haemophilia A in China.
AB  - INTRODUCTION: About 30% of haemophilia A (HA) patients are sporadic cases. It is
      important to confirm the mutation origin and carrier status in these families.
      AIM: To describe the spectrum and origin of the mutations in 393 Chinese sporadic
      HA families and identify potential mosaics among non-carrier mothers. METHODS:
      AccuCopy quantification combined with long-distance PCR was used for genotyping
      intron 22/1 inversion (Inv22/Inv1) and Inv22 mosaicism. F8 gene sequences were
      analysed by direct sequencing. Copy number variations of F8 gene were detected by
      AccuCopy method. Six short tandem repeats related to F8 gene were applied for
      linkage analysis. Mosaicism of point mutations/small deletions/insertions was
      determined by ddNTP primer extension method. RESULTS: Most of sporadic patients'
      mothers are carriers, in 257 cases with integral family members, 60% have the
      mutations tracing back to their fathers, 12% to their mothers. 28% had de novo
      mutations with non-carrier mothers as revealed by routine genetic studies.
      Mutation spectrum of sporadic families was different in groups with different
      origins of mutations. Point mutation (51%) was the predominant mutation type in
      pedigrees with de novo mutations. While, in families with mutations inherited
      from maternal grandfathers, Inv22 was the main type (51%). We found somatic
      mosaic in mothers of 30% (3/10) pedigrees with de novo Inv22 and 11.5% (3/26)
      pedigrees with point mutations. CONCLUSION: The spectrum of F8 genetic variants
      identified in sporadic families was fairly diverse. The high prevalence of
      chimaeras in carriers suggests that more cautions should be taken in genetic
      counselling of sporadic haemophilia families.

PMID- 29381228
TI  - Implications of intercorrelation between hepatic CYP3A4-CYP2C8 enzymes for the
      evaluation of drug-drug interactions: a case study with repaglinide.
AB  - AIMS: Statistically significant positive correlations are reported for the
      abundance of hepatic drug-metabolizing enzymes. We investigate, as an example,
      the impact of CYP3A4-CYP2C8 intercorrelation on the predicted interindividual
      variabilities of clearance and drug-drug interactions (DDIs) for repaglinide
      using physiologically based pharmacokinetic (PBPK) modelling. METHODS: PBPK
      modelling and simulation were employed using Simcyp Simulator (v15.1). Virtual
      populations were generated assuming intercorrelations between hepatic CYP3A4
      CYP2C8 abundances derived from observed values in 24 human livers. A repaglinide
      PBPK model was used to predict PK parameters in the presence and absence of
      gemfibrozil in virtual populations, and the results were compared with a clinical
      DDI study. RESULTS: Coefficient of variation (CV) of oral clearance was 52.5% in
      the absence of intercorrelation between CYP3A4-CYP2C8 abundances, which increased
      to 54.2% when incorporating intercorrelation. In contrast, CV for predicted DDI
      (as measured by AUC ratio before and after inhibition) was reduced from 46.0% in
      the absence of intercorrelation between enzymes to 43.8% when incorporating
      intercorrelation: these CVs were associated with 5th/95th percentiles (2.48-11.29
      vs. 2.49-9.69). The range of predicted DDI was larger in the absence of
      intercorrelation (1.55-77.06) than when incorporating intercorrelation (1.79
      25.15), which was closer to clinical observations (2.6-12). CONCLUSIONS: The
      present study demonstrates via a systematic investigation that population-based
      PBPK modelling incorporating intercorrelation led to more consistent estimation
      of extreme values than those observed in interindividual variabilities of
      clearance and DDI. As the intercorrelations more realistically reflect enzyme
      abundances, virtual population studies involving PBPK and DDI should avoid using
      Monte Carlo assignment of enzyme abundance.

PMID- 29381229
TI  - Time-to-event modelling of effect of codrituzumab on overall survival in patients
      with hepatocellular carcinoma.
AB  - AIMS: Codrituzumab (GC33) is a recombinant, humanized mAb that binds to glypican
      3 (GPC3), an oncofetal protein highly expressed in hepatocellular carcinoma
      (HCC). This investigation aimed to identify clinically relevant factors that may
      affect the overall survival (OS) in HCC patients treated with codrituzumab and to
      quantitatively annotate their effects. METHODS: Codrituzumab exposure was
      estimated by a population pharmacokinetics model with a nonlinear elimination
      pathway. Analysis of OS was performed using a time-to-event model in 181 patients
      with advanced HCC. The model was tested with the addition of various covariates,
      including levels of immune biomarkers, such as CD16 (measured in terms of
      molecules of equivalent soluble fluorophore; CD16MESF ) and CD4, codrituzumab
      exposure and potential prognostic biomarkers of HCC such as baseline tumour size
      and soluble GPC3. RESULTS: The time-to-event model estimated a prolonged OS (>3
      months) in patients with codrituzumab exposure of >=230 MUg ml-1 and high
      CD16MESF level (>5.26 * 105 MESF at least). The Weibull model was selected as the
      base hazard model. The baseline tumour size was included in the hazard model as a
      parameter independent of the drug effect. A logistic model was applied to explain
      the effects of drug exposure and CD16MESF level. CONCLUSIONS: The final model
      indicates that adequate drug exposure plus a favourable immune environment are
      associated with prolonged OS. This quantitative model should be further validated
      with emerging data so as to guide study design in future clinical trials.

PMID- 29381230
TI  - Novel SYNGAP1 variant in a patient with intellectual disability and distinctive
      dysmorphisms.
AB  - We describe a novel de novo heterozygous variant in SYNGAP1 (c.1741C>T, p.R581W),
      identified through targeted resequencing in an 8-year-old boy with intellectual
      disability, autism spectrum disorder, distinctive dysmorphic features, and no
      seizures. Our data strongly suggest that the SYNGAP1 variant is causative of
      intellectual disability in this patient.

PMID- 29381231
TI  - Optimization of reverse chemical ecology method: false positive binding of
      Aenasius bambawalei odorant binding protein 1 caused by uncertain binding
      mechanism.
AB  - Odorant binding proteins (OBPs) are considered as the core molecular targets in
      reverse chemical ecology, which is a convenient and efficient method by which to
      screen potential semiochemicals. Herein, we identified a classic OBP, AbamOBP1
      from Aenasius bambawalei, which showed high mRNA expression in male antennae.
      Fluorescence competitive binding assay (FCBA) results demonstrated that AbamOBP1
      has higher binding affinity with ligands at acid pH, suggesting the
      physiologically inconsistent binding affinity of this protein. Amongst the four
      compounds with the highest binding affinities at acid pH, 2, 4, 4-trimethyl-2
      pentene and 1-octen-3-one were shown to have attractant activity for male adults,
      whereas (-)-limonene and an analogue of 1-octen-3-ol exhibited nonbehavioural
      activity. Further homology modelling and fluorescence quenching experiments
      demonstrated that the stoichiometry of the binding of this protein to these
      ligands was not 1: 1, suggesting that the results of FCBA were false. In
      contrast, the apparent association constants (Ka) of fluorescence quenching
      experiments seemed to be more reliable, because 2, 4, 4-trimethyl-2-pentene and 1
      octen-3-one had observably higher Ka than (-)-limonene and 1-octen-3-ol at
      neutral pH. Based on the characteristics of different OBPs, various approaches
      should be applied to study their binding affinities with ligands, which could
      modify and complement the results of FCBA and contribute to the application of
      reverse chemical ecology.

PMID- 29381232
TI  - Categorization of fetal external findings in developmental toxicology studies by
      the Terminology Committee of the Japanese Teratology Society.
AB  - Categorization of fetal external findings in common laboratory animals, intended
      to make the agreement at Berlin Workshop in 2014 more practical, was proposed by
      the Terminology Committee of the Japanese Teratology Society at the Workshop in
      the 55th Japanese Teratology Society Annual Meeting in 2015. In the Workshop, 73
      external findings, which had been categorized as "Gray zone" anomalies but not as
      "Malformation" or "Variation" in the 2014 Berlin Workshop, were discussed and
      classified as Malformation, "Non-structural abnormality," Variation, and "Not
      applicable." The proposal was based on the results of a survey conducted in 2014,
      where 20 facilities (including pharmaceutical, chemical, and pesticide companies
      and contract laboratories) and 2 selected expert teratologists in Japan were
      asked for their opinions on the categorization of these findings. Based on the
      discussion, Japanese Teratology Society members have agreed that 42 out of the 73
      findings can be classified as Malformations (38), Non-structural abnormalities
      (3), Malformations/Non-structural abnormalities (1), and Variations (0), while
      the remaining 31 findings were recommended to be categorized as Not applicable
      for fetuses. The details of the classification are shown on the website of the
      Japanese Teratology Society (http://www.umin.ac.jp/cadb/External.pdf).

PMID- 29381234
TI  - Balancing early access with uncertainties in evidence for drugs authorized by
      prospective case series - systematic review of reimbursement decisions.
AB  - AIMS: To review clinical and cost-effectiveness evidence underlying reimbursement
      decisions relating to drugs whose authorization mainly is based on evidence from
      prospective case series. METHODS: A systematic review of all new drugs evaluated
      in 2011-2016 within a health care profession-driven resource prioritization
      process, with a market approval based on prospective case series, and a
      reimbursement decision by the Swedish Dental and Pharmaceutical Benefits Agency
      (TLV). Public assessment reports from the European Medicines Agency, published
      pivotal studies, and TLV, Scottish Medicines Consortium and National Institute of
      Health and Care Excellence decisions and guidance documents were reviewed.
      RESULTS: Six drug cases were assessed (brentuximab vedotin, bosutinib, ponatinib,
      idelalisib, vismodegib, ceritinib). The validity of the pivotal studies was
      hampered by the use of surrogate primary outcomes and the absence of recruitment
      information. To quantify drug treatment effect sizes, the reimbursement agencies
      primarily used data from another source in indirect comparisons. TLV granted
      reimbursement in five cases, compared with five in five cases for Scottish
      Medicines Consortium and four in five cases for National Institute of Health and
      Care Excellence. Decision modifiers, contributing to granted reimbursement
      despite hugely uncertain cost-effectiveness ratios, were, for example, small
      population size, occasionally linked to budget impact, severity of disease, end
      of life and improved life expectancy. CONCLUSION: For drugs whose authorization
      is based on prospective case series, most applications for reimbursement within
      public health care are granted. The underlying evidence has limitations over and
      above the design per se, and decision modifiers are frequently referred to in the
      value-based pricing decision making.

PMID- 29381233
TI  - Clinical and genetic features of Charcot-Marie-Tooth disease 2F and hereditary
      motor neuropathy 2B in Japan.
AB  - Mutations in small heat shock protein beta-1 (HspB1) have been linked to Charcot
      Marie-Tooth (CMT) disease type 2F and distal hereditary motor neuropathy type 2B.
      Only four cases with HSPB1 mutations have been reported to date in Japan. In this
      study between April 2007 and October 2014, we conducted gene panel sequencing in
      a case series of 1,030 patients with inherited peripheral neuropathies (IPNs)
      using DNA microarray, targeted resequencing, and whole-exome sequencing. We
      identified HSPB1 variants in 1.3% (13 of 1,030) of the patients with IPNs, who
      exhibited a male predominance. Based on neurological and electrophysiological
      findings, seven patients were diagnosed with CMT disease type 2F, whereas the
      remaining six patients were diagnosed with distal hereditary motor neuropathy
      type 2B. P39L, R127W, S135C, R140G, K141Q, T151I, and P182A mutations identified
      in 12 patients were described previously, whereas a novel K123* variant with
      unknown significance was found in 1 patient. Diabetes and impaired glucose
      tolerance were detected in 6 of the 13 patients. Our findings suggest that HSPB1
      mutations result in two phenotypes of inherited neuropathies and extend the
      phenotypic spectrum of HSPB1-related disorders.

PMID- 29381235
TI  - A Cross-Dehydrogenative Annulation Strategy towards Synthesis of Polyfluorinated
      Phenanthridinones with Copper.
AB  - The first cross-dehydrogenative annulation of (hetero)aromatic amides with
      polyfluoro(hetero)arenes is presented. This operationally simple oxidative
      annulation process is mediated by inexpensive copper salt, accommodates a wide
      range of substrates with exquisite chemo- and regioselectivity profile, and
      produces demanding polyfluorinated phenanthridinones in high yields (up to 92 %).
      Using alkenyl amides under identical conditions, the synthesis of polyfluorinated
      2-quinolones has also been accomplished. Given the importance of fluorinated
      heterocycles in the pharmaceutical industry and drug discovery, this work is
      highly significant.

PMID- 29381236
TI  - Centromeric DNA characterization in the model grass Brachypodium distachyon
      provides insights on the evolution of the genus.
AB  - Brachypodium distachyon is a well-established model monocot plant, and its small
      and compact genome has been used as an accurate reference for the much larger and
      often polyploid genomes of cereals such as Avena sativa (oats), Hordeum vulgare
      (barley) and Triticum aestivum (wheat). Centromeres are indispensable functional
      units of chromosomes and they play a core role in genome polyploidization events
      during evolution. As the Brachypodium genus contains about 20 species that differ
      significantly in terms of their basic chromosome numbers, genome size, ploidy
      levels and life strategies, studying their centromeres may provide important
      insight into the structure and evolution of the genome in this interesting and
      important genus. In this study, we isolated the centromeric DNA of the B.
      distachyon reference line Bd21 and characterized its composition via the
      chromatin immunoprecipitation of the nucleosomes that contain the centromere
      specific histone CENH3. We revealed that the centromeres of Bd21 have the
      features of typical multicellular eukaryotic centromeres. Strikingly, these
      centromeres contain relatively few centromeric satellite DNAs; in particular, the
      centromere of chromosome 5 (Bd5) consists of only ~40 kb. Moreover, the
      centromeric retrotransposons in B. distachyon (CRBds) are evolutionarily young.
      These transposable elements are located both within and adjacent to the CENH3
      binding domains, and have similar compositions. Moreover, based on the presence
      of CRBds in the centromeres, the species in this study can be grouped into two
      distinct lineages. This may provide new evidence regarding the phylogenetic
      relationships within the Brachypodium genus.

PMID- 29381237
TI  - Rapid evolution of a bacterial iron acquisition system.
AB  - Under iron limitation, bacteria scavenge ferric (Fe3+ ) iron bound to
      siderophores or other chelates from the environment to fulfill their nutritional
      requirement. In gram-negative bacteria, the siderophore uptake system prototype
      consists of an outer membrane transporter, a periplasmic binding protein and a
      cytoplasmic membrane transporter, each specific for a single ferric siderophore
      or siderophore family. Here, we show that spontaneous single gain-of-function
      missense mutations in outer membrane transporter genes of Bradyrhizobium
      japonicum were sufficient to confer on cells the ability to use synthetic or
      natural iron siderophores, suggesting that selectivity is limited primarily to
      the outer membrane and can be readily modified. Moreover, growth on natural or
      synthetic chelators required the cytoplasmic membrane ferrous (Fe2+ ) iron
      transporter FeoB, suggesting that iron is both dissociated from the chelate and
      reduced to the ferrous form within the periplasm prior to cytoplasmic entry. The
      data suggest rapid adaptation to environmental iron by facile mutation of
      selective outer membrane transporter genes and by non-selective uptake components
      that do not require mutation to accommodate new iron sources.

PMID- 29381238
TI  - 16S rRNA profiling of the Dermatophagoides farinae core microbiome: Enterococcus
      and Bartonella.

PMID- 29381239
TI  - Grapevine field experiments reveal the contribution of genotype, the influence of
      environment and the effect of their interaction (G*E) on the berry transcriptome.
AB  - Changes in the performance of genotypes in different environments are defined as
      genotype * environment (G*E) interactions. In grapevine (Vitis vinifera), complex
      interactions between different genotypes and climate, soil and farming practices
      yield unique berry qualities. However, the molecular basis of this phenomenon
      remains unclear. To dissect the basis of grapevine G*E interactions we
      characterized berry transcriptome plasticity, the genome methylation landscape
      and within-genotype allelic diversity in two genotypes cultivated in three
      different environments over two vintages. We identified, through a novel data
      mining pipeline, genes with expression profiles that were: unaffected by genotype
      or environment, genotype-dependent but unaffected by the environment,
      environmentally-dependent regardless of genotype, and G*E-related. The G*E
      related genes showed different degrees of within-cultivar allelic diversity in
      the two genotypes and were enriched for stress responses, signal transduction and
      secondary metabolism categories. Our study unraveled the mutual relationships
      between genotypic and environmental variables during G*E interaction in a woody
      perennial species, providing a reference model to explore how cultivated fruit
      crops respond to diverse environments. Also, the pivotal role of vineyard
      location in determining the performance of different varieties, by enhancing
      berry quality traits, was unraveled.

PMID- 29381240
TI  - Erectile dysfunction and testosterone deficiency as cardiovascular risk factors?
AB  - Graham Jackson introduced the concept that erectile dysfunction was a marker for
      undiagnosed cardiovascular disease and future events. Unfortunately this had had
      modest impact on CVD management as ED is not incorporated into current risk
      calculators. In this paper, we examine recent evidence as to whether ED should be
      upgraded to a risk factor, especially with the high predictive value in younger
      men. In the Princeton 3 guidelines, he recognised the important impact of
      testosterone deficiency (TD) on all-cause and cardiovascular mortality. Recent
      evidence suggests that testosterone therapy to target levels and for sufficient
      duration, reduces cardiovascular events. In this paper, we also produce a case
      for testosterone deficiency to be considered as an independent risk factor. The
      evidence for inclusion of both ED and TD may now be stronger than accepted risk
      factors and have the advantages of being easily assessed, being quantitative,
      symptomatic and clinically relevant, especially in younger men.

PMID- 29381241
TI  - Evaluation of inguinal vascular surgical scars treated with closed incisional
      negative pressure wound therapy using three-dimensional digital imaging-A
      randomized controlled trial on bilateral incisions.
AB  - PURPOSE OF THE INVESTIGATION: Scar formation is an important, permanent surrogate
      marker for wound healing. The main aim of this randomized trial was to evaluate
      the effects of incisional negative pressure wound therapy (iNPWT) on scar
      formation in uncomplicated wound healing with 3-dimensional (3D) digital imaging.
      BASIC PROCEDURES: Patients undergoing bilateral inguinal incisions after vascular
      surgery were randomized to receive iNPWT and standard dressing on separate sides.
      The incisional scars were documented at a median time of 808 days (range 394
      1194) after surgery with 3D photography, which were objectively evaluated by two
      plastic surgeons using the Stony Brook scar evaluation scale (SBSES) and a 10
      point graded numeric ranking scale (NRS10). Subjective evaluation was performed
      with the patient observer scar assessment scale (POSAS). Patients with surgical
      site infection or other wound complications were excluded to minimize bias. The p
      values were calculated using McNemar's and Wilcoxon signed-rank test for paired
      nominal and paired continuous data, respectively. MAIN FINDINGS: Among 33
      patients, 32 patients had undergone endovascular aortic repair (EVAR) and 31
      patients had transverse inguinal incisions. Objective and subjective scar
      evaluation showed no difference between iNPWT and standard dressing. In objective
      scorings, 18.8 and 21.9% received the highest possible SBSES total score in the
      iNPWT and standard dressing groups, while 43.8 and 37.5% received the highest
      possible NRS10 score, respectively. The inter-rater reliability between the two
      assessors for SBSES total score and NRS10 showed an intra-class correlation (ICC)
      of 0.78 and 0.68 for NPWT and 0.70 and 0.77 for traditional dressing,
      respectively. PRINCIPAL CONCLUSION: The present randomized trial showed that
      iNPWT and standard dressings on closed transverse inguinal incisions after EVAR
      resulted in equal subtle scar formation. Objective scar evaluation with 3D images
      showed good inter-rater agreement.

PMID- 29381242
TI  - Risk factors for recurrence of pressure ulcers after defect reconstruction.
AB  - Patients suffering from pressure ulcers remain to be a challenging task for
      nursing staff and doctors in the daily clinical management, putting-notably in
      the case of recurrences-additional strain on the constantly reduced resources in
      public healthcare. We aimed to assess the risk factors for the recurrence of
      pressure ulcers at our institution, a tertiary referral center. In this
      retrospective analysis of patients admitted to our division we identified risk
      factors for pressure ulcer recurrence. The hospital patient database search
      included all patients with a diagnosis of pressure ulcers of the torso and lower
      extremity. One hundred sixty-three patients were diagnosed with pressure ulcers
      and 55 patients with 63 pressure ulcers met our inclusion criteria. The 17
      recurrences (27%) had an average follow-up of 728 days. Most presented with
      lesions of the ischial tuberosity (n=24). Recurrence was statistically associated
      with defect size (p = 0.013, Cox regression analysis), and serum albumin levels
      (p = 0.045, Spearman correlation), but no association was found for body mass
      index, bacterial profile, comorbidities, localization, previous surgery, or time
      to-admission for reconstruction (all p > 0.05). Supported by the recent
      literature we identified factors like defect size to be associated with pressure
      ulcer recurrence, but not with time-to admission for reconstruction or number of
      previous debridements. Whether laboratory values like serum albumin levels were
      the cause, the result or associated with pressure ulcer recurrence warrants
      further investigation.

PMID- 29381243
TI  - Neural crest-derived cells migrate from nerve to participate in Achilles tendon
      remodeling.
AB  - During tendon injury, nerve ingrowth is one of the earliest events of tendon
      repair and remodeling. Since peripheral neurons and associated cells are mostly
      derived from neural crest (NC) cells, we sought to investigate the role of NC
      derived cells in tendon regeneration. Thus, we used Sox10-Cre/ROSA26-Flox-Red
      Fluorescent Protein (RFP) transgenic mice to trace these cells during tendon
      regeneration. After 4 weeks of Achilles tendon rupture, the injured tendon
      tissues were harvested for immunohistological analyses, cell isolation, and
      phenotype identification. In addition, the tenocytes were co-cultured with RFP
      labeled cells to examine cellular functions. Following the injury, a significant
      number of RFP-labeled cells penetrated into the wound site and reached a peak
      (~30% of cells) after 2 weeks, and then stabilized at a level of approximately
      20%. Interestingly, 36.9% RFP labeled cells in the injured area expressed Tuj1,
      suggesting that most of the cells are peripheral neurons. Some RFP+ /Tuj1+ cells
      were also found adjacent to newly formed blood vessels in the tendon.
      Importantly, the existing neuropeptide Y (NPY) and neuropeptide Y receptor (NPYr)
      in the invading nerve and blood vessels were directly correlated. In addition,
      there were also RFP+ cells (~30%) negative for neuronal markers but positive for
      fibroblast markers, that is, FAP (34.7%) and Vimentin (Vmt) (27.2%), and
      approximately 10% positive for Sox10. Indeed, many RFP+ cells isolated from the
      ruptured Achilles tendon showed long spindle shapes and expressed fibroblast
      phenotypic markers FSP1 and FAP. Part of the Sox10+ RFP-labeled cells exhibited
      osteogenic and adipogenic differentiation ability. It is concluded that after
      Achilles tendon injury, nerves sprout into the wound site. The NC-derived Vmt+
      /FAP+ mesenchymal cells and peripheral nerves participate in tendon regeneration.

PMID- 29381244
TI  - Pyogenic sacroiliitis and haemophilia-A duo not often considered.

PMID- 29381245
TI  - Congenital bleeding disorders: Report from one tertiary centre in Guatemala.

PMID- 29381246
TI  - Evidence in support of hyperkalaemia management strategies: A systematic
      literature review.
AB  - BACKGROUND: Hyperkalaemia is a potentially life-threatening condition that can be
      managed with pharmacological and non-pharmacological approaches. With the recent
      development of new hyperkalaemia treatments, new information on safe and
      effective management of hyperkalaemia has emerged. OBJECTIVES: This systematic
      literature review (SLR) aimed to identify all relevant comparative and non
      comparative clinical data on management of hyperkalaemia in adults. Our secondary
      aim was to assess the feasibility of quantitatively comparing randomised
      controlled trial (RCT) data on the novel treatment sodium zirconium cyclosilicate
      (ZS) and established pharmacological treatments for the non-emergency management
      of hyperkalaemia, such as the cation-exchangers sodium/calcium polystyrene
      sulphonate (SPS/CPS). METHODS: MEDLINE, Embase and the Cochrane Library were
      searched on 3rd April 2017, with additional hand-searches of key congresses and
      previous SLRs. Articles were screened by two independent reviewers. Eligible
      records reported interventional or observational studies of pharmacological or
      non-pharmacological management of hyperkalaemia in adults. RESULTS: Database
      searches identified 2,073 unique records. Two hundred and one publications were
      included, reporting 30 RCTs, 29 interventional non-RCTs and 43 observational
      studies. Interventions investigated in RCTs included ZS (3), SPS/CPS (3),
      patiromer (4) and combinations of temporising agents (6 RCTs). A robust and
      meaningful indirect treatment comparison between ZS and long-established cation
      binding agents (SPS/CPS) was infeasible because of heterogeneity between studies
      (including time points and dosing) and small sample size in SPS/CPS studies.
      CONCLUSIONS: Despite hyperkalaemia being associated with several chronic
      diseases, there is a paucity of high-quality randomised evidence on long
      established treatment options (SPS and CPS) and a limited evidence base for
      hyperkalaemia management with these agents.

PMID- 29381247
TI  - NREM sleep EEG activity and procedural memory: A comparison between young
      neurotypical and autistic adults without sleep complaints.
AB  - : Delta EEG activity (0.75-3.75 Hz) during non-Rapid eye movement (NREM) sleep
      reflects the thalamo-cortical system contribution to memory consolidation. The
      functional integrity of this system is thought to be compromised in the Autism
      spectrum disorder (ASD). This lead us to investigate the topography of NREM sleep
      Delta EEG activity in young adults with ASD and typically-developed individuals
      (TYP). The relationship between Delta EEG activity and sensory-motor procedural
      information was also examined using a rotary pursuit task. Two dependent
      variables were computed: a learning index (performance increase across trials)
      and a performance index (average performance for all trials). The ASD group
      showed less Delta EEG activity during NREM sleep over the parieto-occipital
      recording sites compared to the TYP group. Delta EEG activity dropped more
      abruptly from frontal to posterior regions in the ASD group. Both groups of
      participants learned the task at a similar rate but the ASD group performed less
      well in terms of contact time with the target. Delta EEG activity during NREM
      sleep, especially during stage 2, correlated positively with the learning index
      for electrodes located all over the cortex in the TYP group, but only in the
      frontal region in the ASD group. Delta EEG activity, especially during stage 2,
      correlated positively with the performance index, but in the ASD group only.
      These results reveal an atypical thalamo-cortical functioning over the parieto
      occipital region in ASD. They also point toward an atypical relationship between
      the frontal area and the encoding of sensory-motor procedural memory in ASD.
      Autism Res 2018, 11: 613-623. (c) 2018 International Society for Autism Research,
      Wiley Periodicals, Inc. LAY SUMMARY: Slow EEG waves recorded from the scalp
      during sleep are thought to facilitate learning and memory during daytime. We
      compared these EEG waves in young autistic adults to typically-developing young
      adults. We found less slow EEG waves in the ASD group and the pattern of
      relationship with memory differed between groups. This suggests atypicalities in
      the way sleep mechanisms are associated with learning and performance in a
      sensory-motor procedural memory task in ASD individuals.

PMID- 29381248
TI  - Association between biofilm and multi/extensive drug resistance in diabetic foot
      infection.
AB  - PURPOSE: We aimed to determine significant risk factors for biofilm production
      and to investigate the association between antimicrobial resistance profile and
      biofilm formation in the bacterial isolates obtained from patients with diabetic
      foot infection (DFI). METHODS: Demographic, clinical, laboratory and outcome data
      of 165 patients, prospectively recorded and followed between January 2008 and
      December 2015 by a multidisciplinary committee, were analysed. Standard
      microbiological methods were adopted. Risk factors associated with biofilm were
      determined by univariate and multivariate analyses. RESULTS: The overall rate of
      biofilm production among 339 wound isolates was 34%. The biofilm production rate
      was significantly higher in Gram-negative micro-organisms (39%) in comparison
      with Gram positives (21%) (P = .01). A. baumannii presented the highest biofilm
      production (62%), followed by P. aeruginosa (52%) and Klebsiella spp. (40%). On
      univariate analysis, significant factors associated with biofilm were antibiotic
      use within last 3 months (OR:2.94, CI: 1.5-5.75, P = .002), recurrent DFI within
      last 6 months (OR:2.35, CI: 1.23-4.53, P = .01), hospitalisation within last 3
      months due to ipsilateral recurrent DFI (OR:2.44, CI: 1.06-5.58, P = .03),
      presence of amputation history (OR: 2.20, CI: 1.14-4.24, P = .01), multidrug
      resistant (MDR) micro-organism (OR: 7.76, CI: 4.53-13.35, P<.001) and extensively
      drug-resistant (XDR) micro-organism (OR:11.33, CI:4.97-26.55, P<.001).
      Multivariate regression analysis revealed two variables to be significant factors
      associated with biofilm: MDR micro-organism (OR: 3.63, CI: 1.58-8.33, P = .002)
      and XDR micro-organism (OR:4.06, CI: 1.25-13.1, P = .01). CONCLUSIONS:
      Multi/extensive drug resistance and previous recurrent DFIs were significantly
      associated with biofilm formation in patients with diabetic foot.

PMID- 29381249
TI  - Reactions in Confined Spaces.

PMID- 29381250
TI  - Perspectives on diabetes mortality as the result of residual confounding and
      reverse causality by common disease.
AB  - Type 2 diabetes (T2D) is associated with major global health burdens, including 2
      to 4 times increased rates of morbidity and mortality from cardiovascular
      disease. However, T2D remains an exclusion diagnosis in individuals with
      arbitrarily elevated blood-glucose levels. While it is well-established that
      diabetes is associated with an elevated risk of cardiovascular disease and
      cancer, it has recently been shown that heart failure and cancer may precede, and
      even contribute to, the development of T2D. In the present review, we have
      summarized these findings and discuss their potential implications for our
      understanding of the T2D disease entity, including its treatment and associated
      increased mortality. We suggest that the existence of a hitherto unrecognized
      distinct T2D subtype, secondary to heart failure and/or cancer, may substantially
      contribute to the excess mortality reported in T2D patients with mild disease.
      Treatment and clinical care of this subtype needs to be defined separately from
      the general T2D phenotype.

PMID- 29381252
TI  - Molecular biology at the cutting edge: A review on CRISPR/CAS9 gene editing for
      undergraduates.
AB  - Disrupting a gene to determine its effect on an organism's phenotype is an
      indispensable tool in molecular biology. Such techniques are critical for
      understanding how a gene product contributes to the development and cellular
      identity of organisms. The explosion of genomic sequencing technologies combined
      with recent advances in genome-editing techniques has elevated the possibilities
      of genetic manipulations in numerous organisms in which these experiments were
      previously not readily accessible or possible. Introducing the next generation of
      molecular biologists to these emerging techniques is key in the modern biology
      classroom. This comprehensive review introduces undergraduates to CRISPR/Cas9
      editing and its uses in genetic studies. The goals of this review are to explain
      how CRISPR functions as a prokaryotic immune system, describe how researchers
      generate mutations with CRISPR/Cas9, highlight how Cas9 has been adapted for new
      functions, and discuss ethical considerations of genome editing. Additionally,
      anticipatory guides and questions for discussion are posed throughout the review
      to encourage active exploration of these topics in the classroom. Finally, the
      supplement includes a study guide and practical suggestions to incorporate
      CRISPR/Cas9 experiments into lab courses at the undergraduate level. (c) 2018 The
      Authors Biochemistry and Molecular Biology Education published by Wiley
      Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular
      Biology, 46(2):195-205, 2018.

PMID- 29381253
TI  - Accuracy and precision of flash glucose monitoring sensors inserted into the
      abdomen and upper thigh compared with the upper arm.
AB  - Nowadays, most Belgian patients with type 1 diabetes use flash glucose monitoring
      (FreeStyle Libre [FSL]; Abbott Diabetes Care, Alameda, California) to check their
      glucose values, but some patients find the sensor on the upper arm too visible.
      The aim of the present study was to compare the accuracy and precision of FSL
      sensors when placed on different sites. A total of 23 adults with type 1 diabetes
      used three FSL sensors simultaneously for 14 days on the upper arm, abdomen and
      upper thigh. FSL measurements were compared with capillary blood glucose (BG)
      measurements obtained with a built-in FSL BG meter. The aggregated mean absolute
      relative difference was 11.8 +/- 12.0%, 18.5 +/- 18.4% and 12.3 +/- 13.8% for the
      arm, abdomen (P = .002 vs arm) and thigh (P = .5 vs arm), respectively. Results
      of Clarke error grid analysis for the arm and thigh were similar (zone A: 84.9%
      vs 84.5%; P = .6), while less accuracy was seen for the abdomen (zone A: 69.4%; P
      = .01). Apart from the first day, the accuracy of FSL sensors on the arm and
      thigh was more stable across the 14-day wear duration than accuracy of sensors on
      the abdomen, which deteriorated mainly during week 2 (P < .0005). The aggregated
      precision absolute relative difference was markedly lower for the arm/thigh (10.9
      +/- 11.9%) compared with the arm/abdomen (20.9 +/- 22.8%; P = .002). Our results
      indicate that the accuracy and precision of FSL sensors placed on the upper thigh
      are similar to the upper arm, whereas the abdomen performed unacceptably poorly.

PMID- 29381251
TI  - Current evidence for the treatment of hypothyroidism with
      levothyroxine/levotriiodothyronine combination therapy versus levothyroxine
      monotherapy.
AB  - OBJECTIVE: Hypothyroidism is relatively common, occurring in approximately 5% of
      the general US population aged >=12 years. Levothyroxine (LT4) monotherapy is the
      standard of care. Approximately, 5%-10% of patients who normalise thyroid
      stimulating hormone levels with LT4 monotherapy may have persistent symptoms that
      patients and clinicians may attribute to hypothyroidism. A long-standing debate
      in the literature is whether addition of levotriiodothyronine (LT3) to LT4 will
      ameliorate lingering symptoms. Here, we explore the evidence for and against
      LT4/LT3 combination therapy as the optimal approach to treat euthyroid patients
      with persistent complaints. METHODS: Recent literature indexed on PubMed was
      searched in March 2017 using the terms "hypothyroid" or "hypothyroidism" and
      "triiodothyronine combination" or "T3 combination." Relevant non-review articles
      published in English during the past 10 years were included and supplemented with
      articles already known to the authors. FINDINGS: Current clinical evidence is not
      sufficiently strong to support LT4/LT3 combination therapy in patients with
      hypothyroidism. Polymorphisms in deiodinase genes that encode the enzymes that
      convert T4 to T3 in the periphery may provide potential mechanisms underlying
      unsatisfactory treatment results with LT4 monotherapy. However, results of
      studies on the effect of LT4/LT3 therapy on clinical symptoms and thyroid
      responsive genes have thus far not been conclusive. CONCLUSIONS: Persistent
      symptoms in patients who are biochemically euthyroid with LT4 monotherapy may be
      caused by several other conditions unrelated to thyroid function, and their cause
      should be aggressively investigated by the clinician.

PMID- 29381254
TI  - Double-stranded RNA targeting calmodulin reveals a potential target for pest
      management of Nilaparvata lugens.
AB  - BACKGROUND: Calmodulin (CaM) is an essential protein in cellular activity and
      plays important roles in many processes in insect development. RNA interference
      (RNAi) has been hypothesized to be a promising method for pest control. CaM is a
      good candidate for RNAi target. However, the sequence and function of CaM in
      Nilaparvata lugens are unknown. Furthermore, the double-stranded RNA (dsRNA)
      target to CaM gene in pest control is still unavailable. RESULTS: In the present
      study, two alternatively spliced variants of CaM transcripts, designated NlCaM1
      and NlCaM2, were cloned from N. lugens. The two cDNA sequences exhibited 100%
      identity to each other in the open reading frame (ORF), and only differed in the
      3' untranslated region (UTR). NlCaM including NlCaM1 and NlCaM2 mRNA was
      detectable in all developmental stages and tissues of N. lugens, with
      significantly increased expression in the salivary glands. Knockdown of NlCaM
      expression by RNAi with different dsRNAs led to an inability to molt properly,
      increased mortality, which ranged from 49.7 to 92.5%, impacted development of the
      ovaries and led to female infertility. There were no significant reductions in
      the transcript levels of vitellogenin and its receptor or in the total
      vitellogenin protein level relative to the control group. However, a significant
      reduction in vitellogenin protein was detected in ovaries injected with dsNlCaM.
      In addition, a specific dsRNA of NlCaM for control of N. lugens was designed and
      tested. CONCLUSION: NlCaM plays important roles mainly in nymph development and
      uptake of vitellogenin by ovaries in vitellogenesis in N. lugens. dsRNA derived
      from the less conserved 3'-UTR of NlCaM shows great potential for RNAi-based N.
      lugens management. (c) 2018 Society of Chemical Industry.

PMID- 29381255
TI  - Airborne and food sensitization patterns in children and adults with eosinophilic
      esophagitis.
AB  - BACKGROUND: The pathogenesis of eosinophilic esophagitis (EoE) is currently
      unknown, but evidence suggests that allergic sensitization to food and airborne
      allergens may play a key role. This retrospective study examines the rate of
      sensitization to both food and airborne allergens in EoE patients, and compares
      their sensitivity patterns to control groups. METHODS: We identified 103 patients
      with a diagnosis of EoE via esophageal eosinophilia (>=15 eosinophils/high-power
      field [hpf]), who had undergone comprehensive food and/or airborne allergen
      testing through either skin or in vitro methods. Food and airborne allergen
      sensitization was defined as positive testing in at least 1 food subgroup (milk,
      peanut, tree nut, seafood/fish, soy, grain, egg) or airborne subgroup (tree,
      grass, weed, mite/cockroach, animal, mold), respectively. The same sensitization
      criterion was applied to allergic rhinitis (AR) patients, with and without a
      clinical suspicion of food allergy (FA), in order to create control groups.
      RESULTS: Sensitization in the EoE group to at least 1 subgroup of food allergen
      and airborne allergen was seen in 77.1% (64/83) and 71.7% (38/53), respectively
      (p = 0.82). There were significant differences in sensitization between EoE and
      control groups for tree nut, soy, grain, and egg, but no differences noted in any
      of the other food or airborne allergen subgroups, even after accounting for age
      and gender. CONCLUSION: EoE and control groups had similar airborne allergen
      sensitization patterns, yet dissimilar food allergen sensitization patterns,
      suggesting that specific allergens may play a more prominent role in the
      pathogenesis of EoE. The EoE group had a more uniform distribution pattern for
      food allergens, compared to controls.

PMID- 29381256
TI  - Isocyanides Derived from alpha,alpha-Disubstituted Amino Acids: Synthesis and
      Antifouling Activity Assessment.
AB  - Herein, we contribute to the development of environmentally friendly antifoulants
      by synthesizing eighteen isocyanides derived from alpha,alpha-disubstituted amino
      acids and evaluating their antifouling activity/toxicity against the cypris
      larvae of the Balanus amphitrite barnacle. Almost all isocyanides showed good
      antifouling activity without significant toxicity and exhibited EC50 values of
      0.07 - 7.30 MUg/mL after 120-h exposure. The lowest EC50 values were observed for
      valine-, methionine-, and phenylalanine-derived isocyanides, which achieved > 95%
      cypris larvae settlement inhibition at concentrations of less than 30 MUg/mL
      without exhibiting significant toxicity. Thus, the prepared isocyanides should be
      useful for further research focused on the development of environmentally
      friendly antifouling agents.

PMID- 29381259
TI  - Nasal valve evaluation in the Mexican-Hispanic (mestizo) nose.
AB  - BACKGROUND: Our aim in this study was to determine the angle of the internal
      nasal valve in Mexican patients with the "mestizo nose" feature and without nasal
      obstructive symptoms. The work was prospective, comparative, and observational in
      nature and included patients >14 years of age who were seen in the Otolaryngology
      Department at the Los Angeles Lomas Hospital between April and May 2016. METHODS:
      The angle of the internal nasal valve was measured in 30 patients without
      obstructive symptoms. Endoscopic examination was performed with a 0 degrees 
      endoscope framed with tape at a 13-mm distance from the endoscope's tip, and
      digital photographs of the internal nasal valve were taken. The measurement of
      the angle of the internal nasal valve was made in sexagesimal degrees using
      Golden Ratio v3.1 (2012) software. Statistical analysis was performed using Excel
      v15.13.3. RESULTS: The angles of the internal nasal valve of the patients were
      (mean +/- standard deviation) 24.07 +/- 4.8 degrees  for the right nasal cavity
      and 25.07 +/- 5.0 degrees  for the left nasal cavity, wider than the angle
      reported in the normal Caucasian nose established in the literature. CONCLUSIONS:
      According to our results, the Mexican-Hispanic mestizo nose has a wider angle in
      the internal nasal valve than that considered normal in the literature (10
      degrees -15 degrees ). We believe it is necessary to undertake a second study and
      add an airflow resistance measurement with a rhinomanometry procedure so we can
      compare the results with those in the Caucasian population.

PMID- 29381257
TI  - Completion of the tuberculosis care cascade in a community-based HIV linkage-to
      care study in South Africa and Uganda.
AB  - INTRODUCTION: Tuberculosis (TB) is the leading cause of HIV-associated mortality
      in Africa. As HIV testing, linkage to care and antiretroviral treatment
      initiation intensify to meet UNAIDS targets, it is not known what effect these
      efforts will have on TB detection and prevention. We aimed to characterize the TB
      care cascade of screening, diagnostic testing, treatment and provision of
      isoniazid preventive therapy (IPT) in a study of community-based HIV screening
      and linkage to care and determine whether symptom screening results affected
      progress along the cascade. METHODS: Between June 2013 and March 2015, HIV
      infected adults enrolled in the Linkages study, a multi-site, community-based,
      randomized HIV screening and linkage-to-care study in South Africa and Uganda.
      All participants were screened for TB symptoms at entry after testing positive
      for HIV and referred to local clinics for care. During the 9 month follow-up,
      participants were periodically surveyed about clinic linkage and initiation of
      HIV care as well as subsequent TB testing, treatment, or IPT. We compared
      outcomes between persons with and without a positive symptom screen at baseline
      using descriptive statistics and Poisson regression to calculate relative risks
      of outcomes along the care cascade. RESULTS AND DISCUSSION: Of the 1,325 HIV
      infected adults enrolled, 26% reported at least one TB symptom at the time of HIV
      diagnosis. Loss of appetite and fever were the most commonly reported symptoms on
      a TB symptom screen. Despite 92% HIV linkage success, corresponding TB linkage
      was incomplete. Baseline TB symptoms were associated with an increased risk of a
      TB diagnosis (relative risk 3.23, 95% CI 1.51 to 6.91), but only 34% of
      symptomatic persons had sputum TB testing. Fifty-five percent of participants
      diagnosed with TB started TB treatment. In South Africa, only 18% of asymptomatic
      participants initiated IPT after linkage to HIV care, and presence of symptoms
      was not associated with IPT initiation (relative risk 0.86 95% CI 0.6 to 1.23).
      CONCLUSIONS: HIV linkage to care interventions provide an opportunity to improve
      completion of the TB care cascade, but will require additional support to realize
      full benefits.

PMID- 29381258
TI  - In Vitro Photodynamic Activity of N-Methylated and N-Oxidised Tripyridyl
      Porphyrins with Long Alkyl Chains and Their Inhibitory Activity in Sphingolipid
      Metabolism.
AB  - A series of N-methylated and N-oxidised tripyridyl porphyrins were synthesised,
      characterised, and their PDT activity was studied with six cell lines. All the
      tested porphyrins with a long alkyl chain, except one, were more efficient for
      PDT than an N-methylated hydrophilic porphyrin and N-oxidised porphyrin without
      the long alkyl chain. Generally, N-methylated tripyridyl porphyrins were more
      active than those N-oxidised, but IC50 values for phototoxicity of two N-oxides,
      named TOPyP3-C17 H33 O and TOPyP3-C17 H35 , were still in the nanomolar
      concentration range for most of the tested cell lines. However, TOPyP3-C17 H35
      did not show phototoxicity on human foreskin fibroblast cells. Two methylated
      amphiphilic porphyrins, named TMPyP3-C17 H33 and TMPyP4-C17 H35, showed
      significant dark toxicity, whereas none of the oxidopyridyl porphyrins were toxic
      without light activation. The selected photosensitisers were shown to be
      apoptosis inducers, and had inhibitory effects on the clonogenic growth of HCT116
      and HeLa cells. All three N-methylated amphiphilic porphyrins significantly
      reduced the migratory potential of HCT116 cells. Porphyrins TMPyP3-C17 H35 and
      TOPyP3-C17 H35 reduced the activity of acid ceramidase, whereas TOPyP3-C17 H33 O
      had a significant inhibitory effect on sphingosine kinase 1 activity in HeLa
      cells. Compounds with this dual activity were shown to be the most promising
      photosensitisers, with potential to treat invasive cancers.

PMID- 29381260
TI  - Risk of second primary malignancy in patients with sinonasal tumors: a population
      based cohort study.
AB  - BACKGROUND: The 5-year overall survival rate for patients with sinonasal cancers
      has remained around 50% for the last 3 decades. Prior studies on head and neck
      cancers have suggested that 1 reason for poor survival is the frequent
      development of second primary malignancies (SPMs). The purpose of this study is
      to assess overall and site-specific risks of SPM following treatment of sinonasal
      malignancy. METHODS: A retrospective, population-based cohort study was performed
      on 2614 patients in the Surveillance, Epidemiology, and End Results (SEER)
      database who were diagnosed with primary sinonasal malignancy between 1973 and
      2014. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were
      calculated to assess risk of SPM relative to incidence in the general population.
      RESULTS: A total of 422 (16.1%) patients with primary sinonasal malignancies
      developed a total of 480 SPMs. This cohort had a significantly higher frequency
      of SPMs than expected in the general population (SIR 1.32; 95% confidence
      interval [CI], 1.20 to 1.44; AER 53.41). Site-specific analyses of SIRs suggested
      highest risk of malignancy in the sinonasal tract (SIR 75.64; 95% CI, 53.53 to
      103.83; AER 17.22), followed by bone, eye and orbit, oral cavity and pharynx, and
      lung and mediastinum. CONCLUSION: Patients with history of sinonasal cancer are
      at significantly increased risk of developing an SPM. Careful monitoring for
      development of additional tumors may be warranted.

PMID- 29381261
TI  - Characterization of the novel HLA allele: B*14:58.
AB  - HLA-B*14:58 differs from B*14:02:01 by a polymorphism at position 506 a C instead
      a G.

PMID- 29381262
TI  - Identification of a novel HLA-C allele, HLA-C*15:151, in a Taiwanese individual.
AB  - One nucleotide substitution in codon 240 of HLA-C*15:02:01:01 results in a novel
      allele, HLA-C*15:151.

PMID- 29381263
TI  - Characterization of the novel HLA-B*07:305 allele by sequencing-based typing.
AB  - HLA-B*07:305 differs from HLA-B*07:02:01:01 by one nucleotide substitution at
      position 255.

PMID- 29381264
TI  - Passage culture of human monocyte/macrophage lineage cells using a temperature
      responsive culture dish.

PMID- 29381265
TI  - Volatiles and Nonvolatiles in Flourensia campestris Griseb. (Asteraceae), How
      Much Do Capitate Glandular Trichomes Matter?
AB  - The distribution and ultrastructure of capitate glandular trichomes (GTs) in
      Flourensia species (Asteraceae) have been recently elucidated, but their
      metabolic activity and potential biological function remain unexplored. Selective
      nonvolatile metabolites from isolated GTs were strikingly similar to those found
      on leaf surfaces. The phytotoxic allelochemical sesquiterpene (-)-hamanasic acid
      A ((-)-HAA) was the major constituent (ca. 40%) in GTs. Although GTs are
      quaternary ammonium compounds (QACs)-accumulating species, glycine betaine was
      not found in GTs; it was only present in the leaf mesophyll. Two (-)-HAA
      accompanying surface secreted products: compounds 4-hydroxyacetophenone (piceol;
      1) and 2-hydroxy-5-methoxyacetophenone (2), which were isolated and fully
      characterized (GC/MS, NMR), were present in the volatiles found in GTs. The
      essential oils of fresh leaves revealed ca. 33% monoterpenes, 26% hydrocarbon-
      and 30% oxygenated sesquiterpenes, most of them related to cadinene and
      bisabolene derivatives. Present results suggest a main role of GTs in determining
      the volatile and nonvolatile composition of F. campestris leaves. Based on the
      known activities of the compounds identified, it can be suggested that GTs in F.
      campestris would play key ecological functions in plant-pathogen and plant-plant
      interactions. In addition, the strikingly high contribution of compounds derived
      from cadinene and bisabolene pathways, highlights the potential of this species
      as a source of high-valued bioproducts.

PMID- 29381267
TI  - Puerto Rico after Hurricane Maria.

PMID- 29381266
TI  - An integrated multi-layered analysis of the metabolic networks of different
      tissues uncovers key genetic components of primary metabolism in maize.
AB  - Primary metabolism plays a pivotal role in normal plant growth, development and
      reproduction. As maize is a major crop worldwide, the primary metabolites
      produced by maize plants are of immense importance from both calorific and
      nutritional perspectives. Here a genome-wide association study (GWAS) of 61
      primary metabolites using a maize association panel containing 513 inbred lines
      identified 153 significant loci associated with the level of these metabolites in
      four independent tissues. The genome-wide expression level of 760 genes was also
      linked with metabolite levels within the same tissue. On average, the genetic
      variants at each locus or transcriptional variance of each gene identified here
      were estimated to have a minor effect (4.4-7.8%) on primary metabolic variation.
      Thirty-six loci or genes were prioritized as being worthy of future
      investigation, either with regard to functional characterization or for their
      utility for genetic improvement. This target list includes the well-known opaque
      2 (O2) and lkr/sdh genes as well as many less well-characterized genes. During
      our investigation of these 36 loci, we analyzed the genetic components and
      variations underlying the trehalose, aspartate and aromatic amino acid pathways,
      thereby functionally characterizing four genes involved in primary metabolism in
      maize.

PMID- 29381268
TI  - New-onset serositis in a kidney transplant patient.

PMID- 29381269
TI  - CDC Grand Rounds: Improving medication adherence for chronic disease management -
      Innovations and opportunities.

PMID- 29381270
TI  - DC Metabolism Controls Lung T Cell Polarization.

PMID- 29381271
TI  - Paroxetine: Into Oblivion?

PMID- 29381272
TI  - Impact of stress on dentists' clinical performance. A systematic review.
AB  - INTRODUCTION: Dentistry is recognised as a stressful profession and dentists
      perceive their profession to be more stressful than other healthcare professions.
      While earlier studies have shown a link between stress and well-being among
      dentists, whether stress negatively impacts their clinical performance is an
      important and open question. We do know, however, that stress is associated with
      reduced performance in other health (and non-health) related professions.
      OBJECTIVES: This systematic review aimed to answer the question: how does stress
      impact on dentists' clinical performance? METHODS: This systematic review was
      registered in PROSPERO (CRD42016045756). The CINHAL, Embase, Medline, PsycINFO,
      EThOS and OpenGrey electronic databases were searched according to PRISMA
      guidelines. Two reviewers independently screened the citations for relevance. The
      citation list of potentially eligible papers was also searched. Prospective
      empirical studies were considered for inclusion. The inclusion criteria were
      applied at the full-text stage by the two same reviewers independently. RESULTS:
      The search yielded 3535 titles and abstracts. Twelve publications were considered
      potentially eligible, eleven of which were excluded as they did not meet the
      predefined inclusion criteria. CONCLUSIONS: This systematic review identified a
      gap in the literature as it found no empirical evidence quantifying the impact of
      stress on dentists' clinical performance. Prospective well-designed experimental
      simulation studies, comparing stress with non-stress situations on clinical
      performance and decision making, as well studies evaluating prospectively real
      life dentists' performance under stress are warranted.

PMID- 29381274
TI  - Pulmonary rehabilitation relieves dyspnea, but does it reduce mortality?

PMID- 29381273
TI  - Community-based nutrition intervention to promote oral health and restore healthy
      body weight in refugee children: a scoping review.
AB  - OBJECTIVE: To determine the scope and quality of evidence on the effectiveness of
      community-based nutrition interventions to promote oral health and restore
      healthy body weight in school-aged refugee children. BASIC RESEARCH DESIGN:
      Scoping review using a systematic approach. MAIN OUTCOME MEASURES: Oral health
      and body weight. RESULTS: Four primary studies, two evaluation studies and one
      systematic review met the inclusion criteria. No nutrition interventions or
      reviews to promote oral health in school-aged refugee children were found. There
      is limited weak evidence for the effectiveness of community-based nutrition
      interventions to restore healthy body weight in refugee settings. A systematic
      review also reported weak evidence of correction of child body weight as a result
      of community-based nutrition interventions in refugee camps. CONCLUSION: This
      scoping review found no community-based nutrition interventions for school-aged
      refugee children to promote oral health and restore healthy body weight. There is
      limited and weak evidence for the effectiveness of community-based nutrition
      interventions to restore healthy body weight in refugee settings. There is a need
      to conduct an early phase study to develop and co-produce community-based
      nutrition interventions to promote oral health and healthy body weight for
      children residing in long-term refugee situations and to investigate the
      feasibility for their implementation.

PMID- 29381275
TI  - ?

PMID- 29381276
TI  - ?

PMID- 29381277
TI  - ?

PMID- 29381278
TI  - ?

PMID- 29381279
TI  - ?

PMID- 29381280
TI  - ?

PMID- 29381281
TI  - ?

PMID- 29381282
TI  - ?

PMID- 29381283
TI  - ?

PMID- 29381284
TI  - 3D Poly(Lactic-co-glycolic acid) Scaffolds for Treating Spinal Cord Injury.
AB  - In this paper, poly(lactic-co-glycolic acid) (PLGA) was used to fabricate spinal
      cord scaffolds using low temperature deposition manufacturing (LDM) technology.
      The PLGA scaffolds were characterized as having good porosity, hydrophilicity and
      considerable biodegradability. The effects of the PLGA scaffolds on cell
      proliferation and cytotoxicity were evaluated by culturing Schwann cells (SCs) on
      the surfaces of the scaffolds. The results showed that the SCs spread and
      proliferated well on the PLGA scaffolds. Histological assessment including Glia
      fibrillary acidic protein (GFAP) staining, Nissl staining, Luxol fast blue (LFB)
      staining and Bielschowsky silver staining showed that the spinal cord recoveries
      considerably improved with the PLGA scaffolds, indicating that the PLGA scaffolds
      exhibited potential for applications in the management of spinal cord injuries.

PMID- 29381285
TI  - Development of Dynamic Liquid and Conjugated Electrospun Poly(L-lactide-co
      caprolactone)/Collagen Nanoyarns for Regulating Vascular Smooth Muscle Cells
      Growth.
AB  - Simulating the modeling of smooth muscle layer in the vascular structure makes a
      great difference for vascular tissue regeneration. A functional tissue engineered
      vascular media shall promote the aligned organization and three-dimensional
      penetration of smooth muscle cells (SMCs) into the scaffold. To this aim, dynamic
      liquid and conjugated nanoyarns based on poly(L-lactide-co-caprolactone) (P(LLA
      CL)) and collagen (COL) with a weight ratio at 3:1 were fabricated by
      electrospinning methods, with random and aligned nanofibers as control groups.
      The Fourier transform infrared spectroscopy and X-ray diffraction analyses
      confirmed the preservation of P(LLA-CL)/COL components and structure. Scanning
      electron microscope (SEM) results indicated a significant increase of yarn
      diameters at 19.27 +/- 6.16 MUm (dynamic liquid) and 10.24 +/- 3.09 MUm
      (conjugated), and both of the nanoyarns had improved mechanical tensile
      properties than the random nanofibers. Compared with random and aligned
      nanofibers, the nanoyarns presented significant higher porosity and larger pore
      diameter, leading to a decrease of water contact angle and a promotion of SMCs
      proliferation and migration. Better SMCs orientation was observed on the
      conjugated nanoyarns, while superior SMCs penetration was achieved on the dynamic
      liquid nanoyarns, owing to the differences in yarns microstructure. Herein, this
      study demonstrated that the aligned and porous P(LLA-CL)/COL nanoyarns fabricated
      by dynamic liquid and conjugated electrospinning were beneficial to regulating
      vascular SMCs outgrowth, which had important implications for functional
      reconstruction of vascular media.

PMID- 29381286
TI  - [Nutrition value of wild-growing fruits from mountain Dagestan and its safety
      after fast freezing and cold storage].
AB  - Results of research of mineral composition, content of vitamin C and P, titrable
      acids, pectinaceous and phenol substances in fresh, fast-frozen (t=-30  degrees
      C), and also stored within 3 and 9 months (t=-18  degrees C) fruits of wild
      growing blackberry, cornel, medlar and sea-buckthorn are presented in article.
      Determination of mineral composition was carried out by flame atomic absorption
      photometry, vitamin C and pectinaceous substances -by titirimetric methods,
      phenolic substances and vitamin P - by colorimetric methods. Vitamin C content
      was minimal in fresh fruits of cornel (6.9+/-0.3 mg%), amounted to 21.7-32.0 mg%
      in the fruits of blackberries and medlar and reached 180.1+/-7.2 mg% in the fruit
      of sea-buckthorn. Vitamin P concentration ranged from 34.9 (sea-buckthorn) to
      180.0 mg% (cornel). Berries of a cornel contained also the greatest number of
      titrable acids (33.2+/-1.3 g/dm3), phenolic compounds (243.0+/-4.8 mg%) and
      pectinaceous substances (2.91+/-0.08%). The most significant content of potassium
      (521+/-15.6 mg%), calcium (133.2+/-5.2 mg%), magnesium (62.4+/-2.5 mg%) and iron
      (2.81+/-0.05 mg%) was revealed in medlar fruits. Consumption of 100 g of the
      studied fruits provides daily requirements of a human body, depending on a
      species of wild plants: in calcium -for 2-13.3%, potassium - for 7.0-20.8%,
      magnesium - for 8.1-15.6%, iron - for 5.9-19.2% and in vitamin C - from 5.8-24.6
      to 145.7% in the case of sea buckthorn. The applied processing method of
      conservation - fast freezing (t=-30  degrees S) of fruits and their long storage
      (t=-18  degrees S) is the effective way ensuring high safety of nutrients in
      them. In the studied berries after 9-months cold storage the safety of vitamin C
      varied ranging from 55.7 (blackberry) to 76.1% (cornel), and vitamin P - from
      81.9 (sea-buckthorn) to 92.8% (cornel). Stability of titrable acids, except for
      medlar fruits, varied from 84.2% (blackberry) to 94.0% (sea-buckthorn). The
      safety of phenolic and pectinaceous compounds by the end of 9 months of storage,
      has averaged 90.6 and 95.6% respectively in comparison with their initial
      quantity in fresh fruits. The mineral composition was the stablest. After
      completion of experiment the safety of mineral substances in fruits of wild
      plants fluctuated from 94.6 to 98.5%. Distinctions in change of biochemical
      complexes of berries of blackberry, cornel, medlar and sea-buckthorn at fast
      freezing (t=-30  degrees S) and storage (t=-18  degrees S), apparently, are
      caused by specific features, content of free and bound water, thickness of
      cellular walls, durability of a thin skin of fruits, as well as by concentration
      of the components that inhibit the destructive processes occurring at the
      cellular and molecular level.

PMID- 29381287
TI  - [The use of the antioxidant drink by healthy workers exposed to chemical
      factors].
AB  - In chemical manufacturing along with alimentary factors, workers are exposed to
      occupational hazards resulting in reduced antitoxic protective properties of the
      organism. The purpose of the present work was to develop a preventive method for
      reducing antitoxic functions of the body of healthy workers exposed to chemical
      factors. We have produced the drink containing carrot juice, honey, olive oil.
      The study involved 50 employees (the average age was 37.4+/-5.5 years) with
      experience of over 15 years. The main group (25 people) were workers with reduced
      antitoxic function who received the drink before each day's work shift for 10
      days, the control group - workers with normal anti-toxic function, which did not
      take a drink. It was found that antioxidant drink intake by healthy employees of
      a chemical complex lead to the decrease of the level of molecules of average mass
      at lambda=254 nm and at lambda=280 nm by 15.1+/-7.2%, the activity of
      gammaglutamyl transferase - by 19.1%, alaninaminotransferase - by 44.1%,
      aspartataminotrans-ferase - by 34.7% (indicators of the syndrome of endogenous
      intoxication), the decrease of the content of malondialdehyde (as an indicator of
      an excessive accumulation of products of lipid peroxidation) - by 43.8%, while
      the activity of catalase, that indicates an increase in the antitoxic functions
      of the organism, increased by 37.5%.

PMID- 29381288
TI  - [About food fortification with vitamins].
AB  - Criticism of attempts to enrich foods (mainly dairy products) with vitamins by
      adding mashed or concentrates of fresh berries and vegetables has been reviewed.
      Concept "enriched (fortified) product" has been considered. It has been shown
      that the addition of fruits and vegetables, which are a source of vitamin C, does
      not increase the content of B vitamins to a level that meets the criteria for
      fortified foods. The differences in the regulations concerning to the degree of
      enrichment of foods are discussed. Development of specific educational programs
      to increase knowledge about vitamins is required not only for the population but
      also for scientific and medical professionals. Keywords: enriched with vitamins
      (fortified) product, fresh berries, vegetables.

PMID- 29381289
TI  - UC-VEGF-SMC Three Dimensional (3D) Nano Scaffolds Exhibits Good Repair Function
      in Bladder Damage.
AB  - We constructed a UC-VEGF-SMC three dimensional (3D) scaffold to explore its
      effect on blood vessel regeneration and bladder repair function in a rabbit model
      with bladder injury. Rabbit adipose tissue-derived stem cells (ADSCs) were
      cultured to construct pluripotent stem cell systems that can be induced to
      differentiate into urothelial cells (UCs) and smooth muscle cells (SMCs). Reverse
      transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent
      assay (ELISA), immunofluorescence, MTT assay and HE staining were used in our
      study. Rabbit models were divided into an experimental group, control group and
      sham group. The bladder histology, urodynamics, smooth muscle function, stent
      degradation rate, urothelial permeability and biomechanical determination of
      rabbits were detected after grafting the scaffold. Correct stem cells based on
      the ADSC surface marker and found that CD90 and CD105 were positive and that CD34
      and CD45 were negative. RT-PCR showed that ADSC-iPS cells expressed the marker
      gene of embryonic stem cells (ESCs), which indicated that Sox2, Klf4, Oct4 and c
      Myc were inserted into the iPS nucleus and that the ADSC-iPS system was
      constructed successfully. Immunofluorescence and MTT assays indicated that iPS
      differentiated into mature SMCs and UCs. ELISA and HEMC culturing methods
      revealed that vascular endothelia growth factor (VEGF) could promote the growth
      of HMECs. Rabbit bladder repair function (urodynamics, smooth muscle function,
      urothelial permeability and biomechanical determination) was stronger in the
      experimental group than in the control group. UC-VEGF-SMC 3D nano scaffold
      exhibits good repair function for bladder damage, which may helpful for treatment
      of damaged bladders.

PMID- 29381290
TI  - [Method of determination organic iodine (iodotyrosines) in food].
AB  - It is important to control the substances of the synthesis of biologically active
      supplements, based on organic forms of iodine (iodotyrosines). But it is no less
      important to control the content of iodotyrosines in foods. The developed method
      is sensitive and selective and can determine iodotyrosines with a lower limit of
      detection (1 ppb). Iodotyrosines have been determined by HPLC-MS/MS. The article
      contains parameters for chromatographic separation of 3-iodo-L-tyrosine and 3.5
      diiodo-L-tyrosine and parameters of the electrospray ionization (ESI) mass
      spectrometry, describes the methodology of sample preparation and solid phase
      extraction. The article substantiates the use of mass spectrometry as the most
      sensitive and selective method for determining the organic iodine as compared to
      HPLC with UV detection. The enzymatic hydrolysis with proteolytic enzymes has
      been used for sample preparation in iodothyronine analyses. Solid phase
      extraction was performed using C18 cartridge. For HPLC-MS/MS analysis
      iodothyronine derivatives were obtained with a mixture of butanol-acetyl
      chloride. Degree of iodotyrosine extraction from the matrix of the foodstuffs was
      not less than 85%, the correlation coefficient of the calibration curve in the
      concentration range of 1-2000 ng/mL was 0.999, reliable determination of iodine
      content in foods in the range from 10 to 20 000 mcg/kg.

PMID- 29381291
TI  - Micron/Submicron Hybrid Topography of Titanium Surfaces Influences Adhesion and
      Differentiation Behaviors of the Mesenchymal Stem Cells.
AB  - To clarify the effects of micron/submicron hybrid topography on cell morphology
      and functionalization, we investigated the adhesion and differentiation of human
      mesenchymal stem cells (hMSCs) to titanium (Ti) surfaces with three different
      topographies: micron, submicron, and hybrid grooves created using a femtosecond
      laser. hMSCs cultured on Ti specimens showed high alignment on micron and hybrid
      surfaces after 6 h of incubation, whereas cells attached to submicron and hybrid
      surfaces were elongated. An examination of vinculin-positive adhesion plaques
      indicated that micron grooves affected cellular alignment by modifying the
      initial cell polarization, whereas submicron grooves affected cellular extension.
      A superposition effect of topography was evidenced by the highly aligned and
      elongated morphology of hMSCs grown on the hybrid surface, which promoted
      osteogenic and chondrogenic differentiation. These findings provide a basis for
      the design of novel biomaterial surfaces that can control specific cellular
      functions.

PMID- 29381292
TI  - Preparation and Characterization of Magnetic and Porous Metal-Ceramic
      Nanocomposites from a Zeolite Precursor and Their Application for DNA Separation.
AB  - In this work, metal-ceramic nanocomposites were obtained through short (up to 2
      h) thermal treatments at relatively moderate temperatures (750-800  degrees C)
      under a reducing atmosphere, using Fe-exchanged zeolite A as the precursor. The
      as-obtained materials were characterized by X-ray powder diffraction analysis, N2
      adsorption at -196  degrees C, and highresolution transmission electron
      microscopy. The results of these analyses showed that the nanocomposites
      consisted of a dispersion of metallic Fe nanoparticles within a porous ceramic
      matrix, mainly based on amorphous silica and alumina. These nanocomposites were
      magnetically characterized, and their magnetic response was studied. Finally, the
      obtained metal-ceramic nanocomposite materials were used in the separation of
      Escherichia coli DNA from a crude cell lysate. The results of the DNA separation
      experiments showed that the obtained materials could perform this type of
      separation.

PMID- 29381295
TI  - Apoptosis Signal-Regulating Kinase 1 (ASK1) Activation is Involved in Silver
      Nanoparticles Induced Apoptosis of A549 Lung Cancer Cell Line.
AB  - Silver nanoparticles (AgNPs) are one of the most important nanomaterials in the
      field of medicine. Our study investigated whether AgNPs induce apoptosis of human
      adenocarcinoma A549 cells and their possible involvement in Apoptosis Signal
      Regulating Kinase 1 (ASK1). The prepared AgNPs had high stability and excellent
      monodispersity. They also possessed inhibitory effect on A549 cells proliferation
      in a concentration-dependent manner by Cell Counting Kit-8 (CCK8) assay and
      Hoechst 33342 Fluorescence. The AgNPs significantly induced production of
      reactive oxygen species (ROS) in A549 cells. We also observed an increased
      cytoplasmic staining of p-ASK1 in cells by immunocytochemical analysis, compared
      with non-treated cells. In addition, we found sequential activation of ASK1, c
      Jun N terminal kinase (JNK), p38 Mitogen Activated Protein Kinase (p38) and
      caspase3 by Western blot after treatment with AgNPs. The AgNPs may thus inhibit
      growth of lung cancer cells and induce apoptosis. The anti-cancer mechanism for
      the AgNPs may be involved in activating the ASK1-JNK/p38-Caspase-3 pathway.

PMID- 29381296
TI  - [The association of genetic polymorphisms with non-communicable disease among
      Arctic population].
AB  - The review analyzed genetic polymorphisms contribute to the development of non
      communicable diseases among the inhabitants of the Arctic. It is known that the
      area belongs to the arctic areas of discomfort for living and employment rights.
      Ecological features of the Far North have contributed to the adaptation of the
      indigenous population to environmental conditions, which manifested itself in
      particular in the power features that provide a low prevalence of obesity,
      metabolic syndrome, type 2 diabetes and cardiovascular disease. Active
      development of the Arctic zone and the associated lifestyle changes in the
      population, including the nature of power, caused a change in the prevalence and
      trends of non-communicable diseases, which has its own characteristics in
      comparison with the ethnic groups living in more southern latitudes. These
      features, as follows from the results of a number of studies to be associated,
      including the presence of genetic polymorphisms characteristic of the population
      of the Arctic zone.

PMID- 29381297
TI  - [Modern trends in study of polymorphism of genes encoding goat's milk proteins].
AB  - This review emphasises the genotypical heterogeneity of the population of goats,
      which at the molecular level is manifested in the form of gene polymorphism in
      the milk proteins. Polymorphic genes, represented in the population of
      heterogeneous alleles, cause a wide variance in the chemical composition and
      processing properties of goat milk. We summarized the literature about the main
      features of genes encoding proteins of goat milk. It is stressed that goat's
      milk, due to genetic polymorphism has a great value when creating a new
      functional food product for children.

PMID- 29381298
TI  - [Characteristics of some indicators of physical development and frequency of
      occurrence of certain somatotypes of women in older age groups].
AB  - The article presents the anthropometric parameters of 251 elderly women (75-90
      years) and 125 long-liver women (90-98 years) of the Slavic ethnic group, living
      in Moscow and Moscow region. Significant differences in basic anthropometric
      characteristics between two age groups have been demonstrated. Average values of
      body weight and height, circumferences and quantities of skin-fat folds were
      significantly lower in long-liver women in compare with representatives of the
      elderly, whereas diameters had no statistical significant differences.
      Somatotypological analysis revealed a frequency of occurrence of different
      somatotypes and prevalence of the three main types among elderly and long-liver
      women - asthenic (32.2-34.0%), pyknic (29.3-30.0%) and europlastic (20.0-21.2%)
      somatotype. Some features of body composition characteristics of elderly and long
      livers women have been demonstrated as well. Estimated absolute amount of bone
      compartment did not differ in two women groups, while relative amount of bone
      compartment in elderly women (15.30+/-0.21%) was lower by 1.11 fold (p<0.05) than
      in long-liver women (17.05++/-0.17%). The content of fat and muscular body
      compartment was significantly (p<0.05) lower in long-liver women as compared with
      the elderly women. The absolute amount of fat body compartment in long-liver
      women was 9.15+/-1.22 vs 13.13+/-0.49 kg in elderly women, the relative amount of
      fat body compartment - 14.39+/-0.26 vs 18.04+/-0.05%; the absolute amount of
      muscular body compartment - 23.04+/-0.26 vs 28.06+/-0.47 kg, the relative amount
      of fat body compartment - 36.22+/-0.15 vs 38.54+/-0.16%.

PMID- 29381299
TI  - [The effect of rutin and hesperidin on the expression of Nrf2- and AhR-regulated
      genes and CYP3A1 gene in rats intoxicated with carbon tetrachloride].
AB  - The purpose of the study was to determine the effects of rutin (R) and hesperidin
      (Hes), the main representatives of two most studied subclasses of flavonoids -
      flavonols and flavanones, on the expression of prototypical Nrf2 and AhR
      regulated genes and CYP3A1 gene in rats intoxicated with carbon tetrachloride
      (CCl4). Investigations were carried out on 5 groups of male Wistar rats with the
      initial body weight (b.w.) 180-200 g (n=40). Rats of the control group and the
      1st experimental group received for 14 days the semisynthetic diet, rats of the
      2nd experimental group - the same diet plus R (400 mg/kg b.w.), the animals of
      the 3rd experimental group received the diet with Hes in the same amount, of the
      4th experimental group - diet with R (400 mg/kg b.w.) and Hes (400 mg/kg b.w.).
      Animals of the experimental groups 24 hours before the end of experiment were
      injected intraperitoneally CCl4 at a dose of 0.5 ml/kg b.w. in olive oil; rats of
      the control group were injected equal amount of olive oil. For gene expression
      assessment the mRNA content of NAD(P)H-quinone oxidoreductase (NQO1), heme
      oxygenase-1 (Hmox1), Nrf2 (Nrf2), AhR (AhR), CYP1A1, CYP1A2, CYP3A1 and beta
      actin (Actb) in rat liver was determined by real-time RT-PCR. The results showed
      that in rats intoxicated with CCl4, enrichment of the diet with R, but not with
      Hes, led to a significant increase in the expression of genes Hmox1, NQO1 and
      CYP3A1. Combined intake of R and Hes with the diet led to additivity of their
      action on the expression of Hmox1 gene and to synergism in the effect on the
      expression of genes NQO1 and CYP3A1. A moderate increase in the levels of
      expression of AhR and CYP1A2 genes as compared to their expression in rats
      treated with CCl4 only, CCl4 and R or CCl4 and Hes has been noted. Thus, for the
      first time on the model of oxidative stress in rats the data have been obtained
      showing at the gene expression level a synergism of action of two flavonoids - R
      and Hes, widely present in the daily human diet.

PMID- 29381300
TI  - [The effect of water with modified isotope (D/H) composition on the reproductive
      function and postnatal development in rats].
AB  - Reproductive parameters and postnatal progeny development were evaluated in 4
      generations of Wistar rats treated with deuterium depleted water (DDW): parental
      (F0), first (F1), second (F2) and third (F3). The experiment was carried out on 2
      groups of animals: experimental group consumed DDW (50 ppm) and control group
      consumed purified tap water (150 ppm). Experiment was consist of a preparatory
      stage, the stage of studying the F0, F1, F2 reproductive parameters and F1, F2,
      F3 postnatal progeny development Reproductive parameters was assessed by F0, F1,
      F2 fertility index and F1, F2, F3 offspring viability and development. Fertility
      index was assessed as the male's ability to fertilize females in the percentage
      of pregnant females/fertilized males to the total number females and males placed
      together for mating. Offspring maturing were evaluated by pups viability,
      development of physical and sexual parameters, emotional and locomotors reflexes
      within the 1st month of life. Group 1 fertility index in F0 females was 100%, in
      F1 and F2 females - 99%, in males all generations - 89-100%. Group 1 F1, F2 and
      F3 offspring viability was high. Number of pups in group 1 F2 offspring was
      higher by 20% than in group 2. Pups of the 1st group F1, F2 and F3 were less
      intensively gained weight from the 1st to the 21st day of life compared with
      group 2, the final weight of the animals in group 1 was higher than in group 2 by
      4-6% from 25th to 30th days of life. Assessment of physical parameters
      development as well as emotional and locomotors reflexes formation did not reveal
      any difference between group 1 and group 2 F1, F2 and F3 offspring. Obtained
      results confirmed that DDW did not effect on rat fertility, viability and
      development of offspring.

PMID- 29381301
TI  - [Investigation of the liver DNA methylation profile of rats under the influence
      of hepatotoxicants of different nature].
AB  - The functional importance of DNA methylation, which is a special case of
      epigenetic variation, is meant for regulation of many biological processes,
      ranged from tissue specific gene expression to remodeling of chromatin structure.
      Disorders of the DNA methylation can cause changes in the cell's phenotype,
      providing a significant impact on the development of pathology. Both exogenous
      and endogenous factors are able to cause disruption of DNA methylation, while
      epigenetic changes usually precede the emergence of clinical and morphological
      symptoms of pathological process development, consequently the parameters of DNA
      methylation can be used as sensitive biomarkers to detect adverse effects on the
      organism. The purpose of the study was to identify genes of the liver, the
      methylation profile of which changes under the influence of hepatotoxicants of
      different nature. The experiment was carried out on 60 male Wistar rats with
      initial body weight (b.w.) 83.3+/-1.5 g. Animals were randomly divided into 6
      groups - 1 control and 5 test groups, with 10 rats in each group. During the
      first two weeks of the experiment the rats of the 1-5th test groups were
      administered to aflatoxin B1 (200 Mg/kg b.w.), cadmium chloride 2,5-hydrate (2
      mg/kg), monosodium glutamate (1000 mg/kg), epigallocatechin gallate (EGCG) (1000
      mg/kg), paracetamol (150 mg/kg), accordingly. Methylation of the liver genes in
      rats was determined by using high-performance methods, based on bisulfite
      sequencing of reduced representation. For each sample from 12 to 30 million pairs
      of reads were received, genes which demonstrated significant changes in
      methylation when exposed to toxic factors were identified: aflatoxin B1 caused
      changes in the methylation of 57 genes; cadmium - 54 genes; monosodium glutamate 
      39 genes; EGCG -198 genes; paracetamol - 167 genes. The comparison of genes with
      altered methylation in the experimental groups revealed that none of the genes
      repeatedly occurred under the influence of each toxicant out of five, the highest
      number of repeats accounted 3. As a result of the present analysis 7 genes have
      been selected: methylation change in Fan1 gene was observed when exposed to
      cadmium, monosodium glutamate, EGCG; gene Lppr2 - under the influence of
      aflatoxin B1, EGCG, paracetamol; gene Mlh3 - under the influence of aflatoxin B1,
      cadmium, paracetamol; Sirt7 gene - under the influence of cadmium, EGCG,
      paracetamol; gene Fbxo15 - when exposed to cadmium, monosodium glutamate,
      paracetamol; gene E2f1 - when exposed to cadmium, EGCG, paracetamol; gene Mrps16 
      when exposed to cadmium, EGCG, paracetamol. On the basis of the received data
      the project of the panel of genes-biomarkers of toxic effect, including genes
      Fan1, Lppr2, Mlh3, Sirt7, Fbxo15, E2f1, Mrps16 has been formed.

PMID- 29381302
TI  - [The study of the contamination and the levels of Campylobacter spp. during the
      processing of selected types of foods].
AB  - The purpose of the work was to study the nature of the Campylobacter spp.
      contamination during the processing of food products of plant and animal origin
      (raw poultry and beef meat, raw milk, leafy salads, sliced raw vegetables). In
      the study of 148 samples 50 strains of Campylobacter spp. (33.8%) were found. For
      the main phenotypic characteristics they were identified as C. jejuni spp. jejuni
      and C. jejuni spp. doylei (over 75%). The highest level of detection of
      campylobacteria (over 45%) was set for raw poultry, including the carcasses of
      chickens broilers, quails, turkeys and their semi-finished products. 19 of the 27
      strains from poultry were identified as C. jejuni. Among the strains isolated
      from the environment, including swabs from equipment surfaces, 91% of the
      isolates were also presented by C. jejuni. It was found that the investigated
      foodstuffs were characterized by high levels of contamination with bacteria of
      the family Enterobacteriaceae, the content of which was comparable with the
      identified values of total viable bacteria (cfu). Salmonella was detected in 19%
      of the investigated poultry samples and in 14.3% of raw cow milk. In the study of
      swabs from surfaces of poultry processing equipment, the frequency of detection
      of Campylobacter strains was 38.7%, Salmonella - 12.9%. Most commonly
      Campylobacter and Salmonella were detected in the zones of primary processing of
      poultry: the frequency of isolation of Salmonella in slaughter corner was 25%,
      Campylobacter - 43%. When testing the swabs taken in the cooking zone of "fast
      food" restaurants Campylobacter and Salmonella were not detected. For studying
      the swabs from equipment surfaces and the environment for the presence of
      Campylobacter spp. a modified technique of sampling was developed. The method
      includes a comprehensive analysis in the test area with the use of three types of
      media for transportation and incubation of Campylobacter spp. (Preston broth with
      blood, Brucella broth, Cary-Blair medium), that increase the probability of
      detection of these pathogens.

PMID- 29381303
TI  - [The association between diet and the probability of colorectal cancer among the
      population of Perm krai: epidemiological study].
AB  - Colorectal cancer (CRC) is one of the main causes of morbidity and mortality
      among all malignant tumors both in the world and in Russia. The purpose of the
      research was to study the association between diet and the probability of CRC in
      Perm Krai. The epidemiological analytical case-control study was performed. The
      questionnaire survey included 191 histologically proved colorectal cancer cases
      and 200 healthy individuals with excluded CRC by the results of colonoscopy. The
      surveyed groups were spread evenly by sex, age, ethnicity, place of residence and
      smoking (p>0.05). The odds to determine the following factors were higher in case
      group: diet including fried foods (OR=2.45, 95% CI: 1.58-3.80, p<0.0001), bread
      more 100 g per day (OR=1.72, 95% CI: 1.72-2.60, r=0.005), over-salted food
      (OR=1.97, 95% CI: 1.27-3.04, p=0.001), consumption of spicy foods (OR=2.82, 95%
      CI: 1.59-5.13, p<0.0001) and dairy products less than 500 g per week (OR=3.94,
      95% CI: 2.60-5.97, p<0.0001). The odds to determine the following factors were
      higher in control group: an exclusion of processed (OR=0.45, 95% CI: 0.28-0.70,
      p<0.0001) and red meat (OR=0.19, 95% CI: 0.05-0.51, p<0.0001). Consequently, at
      the present study the diet factors that have a higher rate in group of CRC
      patient's compared to healthy individuals have been determined. This requires to
      study interaction between diet, another environmental and genetic factors.

PMID- 29381304
TI  - [Evaluation of selenium consumption by Mongolian residents].
AB  - Selenium is one of the essential elements which adequate consumption is strictly
      necessary for human health. Despite unfavorable geographical position of Mongolia
      and registered cases of selenium deficiency diseases among domestic animals in
      some provinces of the country there are still no concrete data of selenium
      content in objects of the environment in this region. The aim of the present work
      was the evaluation of selenium consumption levels by adults from different
      provinces of Mongolia and the development of methods of prophylactic for the
      selenium status optimization. Detection of selenium deficiency in Mongolia was
      caused by inadequate selenium content in foodstuffs. Determined mean consumption
      levels were equal to 41.8+/-4.9 MUg/day for males and 34.1+/-3.1 MUg/day for
      females. The main reason of low selenium content in the diet was its deficiency
      in native foodstuffs: selenium concentrations in meat of domestic animals MUg/kg
      d.w.) reached 109-296 in beef, 94-200 in mutton, 120-225 in horseflesh and 124
      197 in goat's flash, values did not differ between each other statistically
      (p>0.05). The exception were samples of horseflash with selenium concentration
      exceeding 400 MUg/kg d.w. from Gov-Altai province. Selenium content in wheat was
      in the range 6-36MUg/kg d.w., with the lowest levels in Dornod, Ucs and Selenge
      provinces. Selenium content in eggs was equal 6.7-7.8 MUg/egg. The correction of
      selenium deficiency is recommended to achieve using preparations of Astragalus
      Mongolicus from Bulgan province with selenium concentration 278+/-26MUg/kg d.w.
      Besides this utilization of Mongolicum Tricholoma Mushrooms (from the vicinity of
      Ulaanbaatar and from Zavkhan province) seems to be highly promising due to high
      selenium concentrations (616+/-26 MUg/kg d.w. and 352+/-17MUg/kg d.w.
      respectively).

PMID- 29381305
TI  - [The vitamin status of pregnant women in Moscow: effect of multivitamin-mineral
      supplements].
AB  - Examination of the vitamin status of 102 pregnant women (19-41 years old) from
      Moscow (gestational age 6-38 weeks) in winter and spring 2015 has been conducted.
      The lack of vitamin B2 (blood serum level of riboflavin <5 ng/ml), D (25(OH)D
      level <30 ng/ml) and beta-carotene (<20 mg/dL) occurred in 49-66% of pregnant
      women. The percentage of persons with reduced serum levels of vitamin B6 (<4.8
      mg/l), folic acid (<3 mg/l), vitamin A (<30 mg/dL), and E (<0.8 mg/dl) was
      insignificant and amounted 6-8%. All of the women had an adequate supply with
      vitamins C (>0.4 mg/dL) and B12 (>150 ng/L). The frequency of the combined
      deficiency of two vitamins was 29%, of three vitamins - 21%, four - 10%, five -
      5%. Only 8% of women were sufficiently supplied with all 8 studied vitamins and
      beta-carotene. A positive correlation (p<0.001) between the concentration of
      vitamin E and gestation term occurred. beta-Carotene blood serum level raised
      with increasing gestation term in women receiving multivitamin-mineral
      supplements (VMS) and directly correlated (p<0.05) with vitamin E serum level. In
      63 women who were not taking VMS, blood serum level of vitamins A, D, C, B2, B6,
      B12, folic acid and beta-carotene was lower, and the frequency of inadequate
      supply, on the contrary, was significantly higher, compared to 39 women receiving
      VMS. Blood serum concentration of vitamins C, A, D, B6 and folic acid in women
      who were not taking VMS was significantly reduced (p<0.05) with increasing
      gestation term, whereas in women consuming VMS vitamin blood serum level was
      maintained at a constant level. The data obtained demonstrate advisability of VMS
      intake during pregnancy to maintain vitamin status of pregnant women at a
      satisfactory level and to reduce the risk of birth defects in infants.

PMID- 29381306
TI  - [Current aspects of counteraction of foodstuff's falsification].
AB  - Food products are the objects of the consumer's market, and human's health and
      life are directly depended on these product's quality and safety. In this regard,
      the government is paying close attention to entrepreneurial activity aimed at the
      production and turnover of food products, including their realization to the
      final consumer. In the absence of proper state control, designed to ensure, first
      of all, the quality and safety of food products, the consequences may be more
      than the negative. A significant risk to public health can represent some of the
      falsification of food products. Typically, these are species of assortment
      counterfeiting, which may lead to the use of hazardous raw substitutes. In
      general, the falsification is divided into: assortment, qualitative,
      quantitative, informational, cost and complex. Herewith it should be noted that
      falsification in reality is consumer frand and it's necessary to fight against it
      on the State and social levels. Accordingly the ideology of the measures aimed at
      prevention and punishability of food products falsification has been proposed.

PMID- 29381307
TI  - When quality fails patients: finding the best in diabetes care.
AB  - Authors from the Mayo Clinic discuss situational goals in diabetes care, because
      quality targets enforced too strictly may harm patients who are working hard to
      manage their disease.

PMID- 29381308
TI  - Getting to better care and outcomes for diabetes through measurement.
AB  - Authors from the National Quality Forum discuss development of the next
      generation of diabetes measures, including those that reflect "the voice of the
      patient."

PMID- 29381309
TI  - Measuring the quality of diabetes care.
AB  - An introduction to the Joslin Clinical Analytic Tool, a new diabetes measure
      developed to adjust for the variety in patient mix and better inform clinicians
      which interventions will work best.

PMID- 29381310
TI  - The role of the clinical pharmacist in achieving clinical and quality outcomes in
      diabetes management.
AB  - Medication therapy management is a key component of ensuring good outcomes in
      diabetes care. The clinical pharmacist can play a key role in ensuring good
      transitions of care, avoiding problems of polypharmacy, addressing financial
      issues, and providing patient education.

PMID- 29381311
TI  - Impact of the Coventry complex case management program in the Kentucky Medicaid
      population.
AB  - A case management program implemented by Coventry Healthcare in one of the
      nation's poorest areas produced positive, measurable results among patients with
      diabetes.

PMID- 29381312
TI  - Evidence for the benefit of targeted proteomics in the era of the "big data"
      approach.
AB  - The availability of a novel predictive biomarker in diabetes care could have
      benefits for patients, payers, and pharma.

PMID- 29381313
TI  - Demystifying "patient-centered" care in type 2 diabetes: the role of systematic
      measurement.
AB  - Questionnaires are noninvasive, inexpensive measures that can identify key
      elements of the patient perspective that are important for the achievement of
      better outcomes in diabetes care.

PMID- 29381314
TI  - [Flavouring estimation of quality of grape wines with use of methods of
      mathematical statistics].
AB  - The questions of forming of wine's flavour integral estimation during the tasting
      are discussed, the advantages and disadvantages of the procedures are declared.
      As investigating materials we used the natural white and red wines of Russian
      manufactures, which were made with the traditional technologies from Vitis
      Vinifera, straight hybrids, blending and experimental wines (more than 300
      different samples). The aim of the research was to set the correlation between
      the content of wine's nonvolatile matter and wine's tasting quality rating by
      mathematical statistics methods. The content of organic acids, amino acids and
      cations in wines were considered as the main factors influencing on the flavor.
      Basically, they define the beverage's quality. The determination of those
      components in wine's samples was done by the electrophoretic method "CAPEL".
      Together with the analytical checking of wine's samples quality the
      representative group of specialists simultaneously carried out wine's tasting
      estimation using 100 scores system. The possibility of statistical modelling of
      correlation of wine's tasting estimation based on analytical data of amino acids
      and cations determination reasonably describing the wine's flavour was examined.
      The statistical modelling of correlation between the wine's tasting estimation
      and the content of major cations (ammonium, potassium, sodium, magnesium,
      calcium), free amino acids (proline, threonine, arginine) and the taking into
      account the level of influence on flavour and analytical valuation within fixed
      limits of quality accordance were done with Statistica. Adequate statistical
      models which are able to predict tasting estimation that is to determine the
      wine's quality using the content of components forming the flavour properties
      have been constructed. It is emphasized that along with aromatic (volatile)
      substances the nonvolatile matter - mineral substances and organic substances -
      amino acids such as proline, threonine, arginine influence on wine's flavour
      properties. It has been shown the nonvolatile components contribute in
      organoleptic and flavour quality estimation of wines as aromatic volatile
      substances but they take part in forming the expert's evaluation.

PMID- 29381315
TI  - [Investigation of the composition of biologically active substances in extracts
      of wild plants].
AB  - The article presents the research materials of composition and the properties of
      biologically active compounds of aqueous ethanolic extracts of wild plants. To
      obtain extracts, we used raw plants containing phenolic compounds and aromatic
      wild plants: the herb St. John's wort (Hypericum), thyme herba (Thymus vulgaris),
      yarrow (Achillea millefolium), oregano (Origanum vulgaris); leaves of sage
      (Salviae folium); rose hips (Rosae), hawthorn fructus (Crataegus) and fruits of
      mountain ash (Sorbus). The optimum composition of the mixtures used and time of
      extraction has been established: the ratio of alcohol and water in extracting
      mixtures 1:1 by volume; ratio raw material:extractant - 1:7 by weight. The total
      content of fenolic substances in extracts of herbaceous plants varied from to
      15.5 to 24.4 mg/g, and in fruit extracts from 24.2 to 29.7 mg/g. Substances of
      phenolic nature, including gallic and ferulic acid, rutin, hesperidin, quercetin
      and apigenin were identified in the studied extracts using the HPLC. The analysis
      of flavonoid composition showed that rutin content in the investigated extracts
      varied from 0.56 mg/g up to 13,80 mg/g, of quercetin - from 0.52 to 1.36 mg/g;
      apigenin - from 0.44 to 1.44 mg/g; hesperidin from 2.44 to 32,72 mg/g. The
      content of phenolic acids varied from 0.16 to 1.44 mg/g (ferulic acid) and from
      0.16 to 3.12 mg/g (chlorogenic acid). Total antioxidant activity of the studied
      phytoextracts (dilution 1:10) ranged from 142 to 230 MUg/ml (in terms of ascorbic
      acid), which is consistent with the results of the quantitative analysis of
      flavonoids. The results of the studies of antimicrobial properties of
      phytoextracts showed that for E. coli the most active extracts were from thyme
      and yarrow, and against S. aureus - from St. John's wort. Extracts of St. John's
      wort and yarrow were effective against Rhizopus stolonifer.

PMID- 29381316
TI  - [Expansion of the range of anthocyanin food colorants from unconventional vegetal
      primary products].
AB  - The purpose of work to study the content of anthocyanins and other biologically
      active substances in residues of fruits of Sanberri from receivingjuice and mash.
      It is established that residues contained over 70% solids, more than 60% of
      dietary fiber, to 55.4 mg/% of ascorbic acid and up to 90.0 mg/% of anthocyanins.
      Furthermore, they possessed high antioxidant activity (156.8-399.4 mg/%
      dihydroquercetin equivalent) that allowed to recommend them as raw materials for
      receiving natural food colorants. The concentrated food dye from Sanberri's
      residue (50-51% soluble solids) had intensive color varying from dark-violet (at
      acidity of 1.0%) to claret-red (at acidity of 3.0%), possessed high antioxidant
      activity (1308.2-2223.5 mg/%) and contained a large amount of anthocyanins (666
      976 mg/%).

PMID- 29381317
TI  - [Scientific bases and technological principles of the production of gerodietetic
      canned milk].
AB  - It is well known that aging is the natural growing multisection biological
      process inevitably leading to limitation of body adaptive capabilities. The body
      ageing is the result of self-regulation mechanism limitation, reduction of their
      potential capabilities at molecular-genetic, energetic, cellular and general
      regulatory levels. It should be noted that due to lack of the unified theory of
      aging the importance of nutrition factor has been acknowladged particularly
      initiation and intensity of the process, and the role of antioxidants is
      discussed much in detail. As the result of long term investigations at model and
      natural objects the technologies of powder and condensed sterilized gerodietetic
      milk based preserved foods have been developed. The multicomponent receipts
      modules balanced by fatty-acid and amino-acid composition as well as enriched
      with lycopene have been theoretically substantiated and realized. The new
      gerodietetic products are characterized by the following coefficients of RL3/RL6
      not less than for the products: powdered - 0.871/0.615 and condensed sterilized -
      0.883/0.648. The following amino-acid balance of Rp/sigma protein for the
      products: powdered - 0.46/15.00, condensed -0.44/15.76 has been obtained. The
      obtained velues of the balanced criteria of the protein-lipid composition of the
      product are higher comparing to similar values for milk fat and protein. Two
      lycopene dosages in the products are provided: prophylactic - 5 mg and
      antioxidant - 1.5 mg in 400 ml of the reconstituted milk. On the basis of the
      carried out studies two technologies of the manufacture of condensed milk
      gerodietetic products adapted to actual conditions of concentrated milk factories
      have been developed.

PMID- 29381318
TI  - Atomic Layer Deposition of V1-xMoxO2 Thin Films, Largely Enhanced Luminous
      Transmittance, Solar Modulation.
AB  - V1-xMoxO2 thin films were fabricated by nanolamination of VO2/MoO3 alternating
      layers using atomic layer deposition (ALD) process, in which tetrakis-dimethyl
      amino vanadium(IV) [V(NMe2)4] and molybdenum hexacarbonyl(VI) [Mo(CO)6] were used
      as vanadium and molybdenum precursors, respectively. The dopant content of V1
      xMoxO2 films was controlled by adjusting MoO3 cycle percentage (PMo) in ALD pulse
      sequence, which varied from 2 to 10%. Effects of PMo on V1-xMoxO2 crystal
      structure, morphology, semiconductor-to-metal transition properties, and optical
      transmittance were studied. A linear reduction of phase transition temperature
      (Tc) by approximately -11  degrees C/cycle % Mo was observed for V1-xMoxO2 films
      within PMo <= 5%. Notably, dramatic enhanced luminous transmittance (Tlum =
      63.8%) and solar modulation (DeltaTsol = 23.5%) were observed for V1-xMoxO2 film
      with PMo = 7%.

PMID- 29381319
TI  - Tunable Mechanical, Antibacterial, and Cytocompatible Hydrogels Based on a
      Functionalized Dual Network of Metal Coordination Bonds and Covalent
      Crosslinking.
AB  - Tissue engineering has become a rapidly developing field of research because of
      the increased demand from regenerative medicine, and hydrogels are a promising
      tissue engineering scaffold because of their three-dimensional structures. In
      this study, we constructed novel hydrogels of gelatin methacrylate (GelMA)
      hydrogels modified with histidine and Zn2+ (GelMA-His-Zn(II)), which possessed
      fascinating antibacterial properties and tunable mechanical properties because of
      the formation of a functionalized dual network of covalent crosslinking and metal
      coordination bonds. The introduction of metal coordination bonds not only
      improves the strength of the GelMA hydrogels with covalent crosslinking but also
      makes their mechanical properties tunable via adjustments to the concentration of
      Zn2+. The synergistic effect of Zn2+ and the imidazole groups gives the GelMA-His
      Zn(II) hydrogels fascinating antibacterial properties (up to 100% inhibition).
      Counting the colony forming units and compression tests confirmed the fascinating
      antibacterial abilities and tunable mechanical properties, respectively, of the
      GelMA-His-Zn(II) hydrogels. In addition, Cell Counting Kit-8 assays, cytoskeletal
      staining assays, and live/dead assays confirmed the excellent cytocompatibility
      of the GelMA-His-Zn(II) hydrogels. Therefore, the GelMA-His-Zn(II) hydrogels are
      promising for applications in tissue engineering.

PMID- 29381320
TI  - Electrochemical Behavior and Redox-Dependent Disassembly of Gallic Acid/FeIII
      Metal-Phenolic Networks.
AB  - Metal-phenolic networks (MPNs) are a versatile class of organic-inorganic hybrid
      systems that are generating interest for applications in catalysis, bioimaging,
      and drug delivery. These self-assembled MPNs possess metal-coordinated structures
      and may potentially serve as redox-responsive platforms for triggered disassembly
      or drug release. Therefore, a comprehensive study of the reduction and oxidation
      behavior of MPNs for evaluating their redox responsiveness, specific conditions
      required for their disassembly, and the kinetics of metal ion release, is
      necessary. Using a representative MPN gallic acid-iron (GA/FeIII) system, we
      conducted electrochemical studies to provide fundamental insights into the redox
      behavior of these MPNs. We demonstrate that GA/FeIII is redox active, and
      evaluate its electrochemical reversibility, identify the oxidation state of the
      redox-active species, and provide information regarding the stability of the
      networks toward reductive stimuli and specific redox conditions required for the
      "on-off" or continuous release of FeIII. Overall, through studying the redox
      properties of GA/FeIII films, we advance the understanding of multifunctional
      iron-containing MPN platforms that may have practical significance for
      biologically relevant applications.

PMID- 29381321
TI  - NiFe-Layered Double Hydroxide Nanosheet Arrays Supported on Carbon Cloth for
      Highly Sensitive Detection of Nitrite.
AB  - Excessive uptake of nitrite has been proven to be detrimental to the ecological
      system and human health. Hence, there is a rising requirement for constructing
      effective electrochemical sensors to precisely monitor the level of nitrite. In
      this work, NiFe-layered double hydroxide nanosheet arrays (NiFe-LDH NSAs) have
      been successfully fabricated on a carbon cloth (CC) substrate via a facile one
      pot hydrothermal route. By integrating the collective merits of macroporous CC
      and NiFe-LDH NSAs such as superior electrical conductivity, striking synergistic
      effect between the dual active components, enlarged electrochemically active
      surface area, unique three-dimensional hierarchical porous network
      characteristics, and fast charge transport and ion diffusion, the proposed NiFe
      LDH NSAs/CC architecture can be served as a self-supporting sensor toward nitrite
      detection. As a consequence, the resulting NiFe-LDH NSAs/CC electrode
      demonstrates superior nitrite sensing characteristics, accompanied by broad
      linear range (5-1000 MUM), quick response rate (ca. 3 s), ultralow detection
      limit (0.02 MUM), and high sensitivity (803.6 MUA.mM-1.cm-2). Meanwhile, the
      electrochemical sensor possesses timeless stability, good reproducibility, and
      strong anti-interference feature. Importantly, the resulting sensor can determine
      nitrite level in tap and lake water with high recoveries, suggesting its
      feasibility for practical applications. These findings show that the obtained
      NiFe-LDH NSAs/CC electrode holds great prospect in highly sensitive and specific
      detection of nitrite.

PMID- 29381322
TI  - Three-Dimensional Nanofibrous Air Electrode Assembled With Carbon Nanotubes
      Bridged Hollow Fe2O3 Nanoparticles for High-Performance Lithium-Oxygen Batteries.
AB  - Lithium-oxygen batteries have been considered as one of the most viable energy
      source options for electric vehicles due to their high energy density. However,
      they are still faced with technical challenges, such as low round-trip efficiency
      and short cycle life, which mainly originate from the cathode part of the
      battery. In this work, we designed a three-dimensional nanofibrous air electrode
      consisted of hierarchically structured carbon nanotube-bridged hollow Fe2O3
      nanoparticles (H-Fe2O3/CNT NFs). Composite nanofibers consisted of hollow Fe2O3
      NPs anchored by multiple CNTs offered enhanced catalytic sites (interconnected
      hollow Fe2O3 NPs) and fast charge-transport highway (bridged CNTs) for facile
      formation and decomposition of Li2O2, leading to outstanding cell performance:
      (1) Swagelok cell exhibited highly reversible cycling characteristics for 250
      cycles with a fixed capacity of 1000 mAh g-1 at a current density of 500 mA g-1.
      (2) A module composed of two pouch-type cells stably powered an light-emitting
      diode lamp operated at 5.0 V.

PMID- 29381323
TI  - Polarization Effects in Graded AlGaN Nanolayers Revealed by Current-Sensing and
      Kelvin Probe Microscopy.
AB  - We experimentally demonstrate that the conductivity of graded AlxGa1-xN increases
      as a function of the magnitude of the Al concentration gradient (%Al/nm) due to
      polarization doping effects, without the use of impurity dopants. Using three
      up/down-graded AlxGa1-xN nanolayers with Al gradients ranging from ~0.16 to
      ~0.28%Al/nm combined in one structure, the effects of polarization engineering
      for localized electric fields and current transport were investigated. Cross
      sectional Kelvin probe force microscopy and conductive atomic force microscopy
      were used to directly probe the electrical properties of the films with spatial
      resolution along the thickness of the growth. The experimental profiles of the
      built-in electric fields and the spreading current found in the graded layers are
      shown to be consistent with simulations of the field distribution as well as of
      the electron and hole densities. Finally, it was directly observed that for
      gradients less than 0.28%Al/nm the native n-type donors still limit polarization
      induced hole doping, making p-type conductivity still a challenge due to
      background impurities and defects.

PMID- 29381324
TI  - Fetal Kinematics: Basic Outcomes and Translational Outlook.
AB  - This Viewpoint examines recent developments in the quantitative characterization
      of fetal movements via kinematical analysis. We contend that fetal kinematics
      represents a powerful tool to investigate prenatal cognition and the prepostnatal
      continuity of cognitive development. The potential benefits of increased
      investigation into the kinematics of fetal movement are manifold, and apply to
      diverse fields including pediatric medicine and developmental biology.

PMID- 29381326
TI  - Role of Acid-Base Equilibria in the Size, Shape, and Phase Control of Cesium Lead
      Bromide Nanocrystals.
AB  - A binary ligand system composed of aliphatic carboxylic acids and primary amines
      of various chain lengths is commonly employed in diverse synthesis methods for
      CsPbBr3 nanocrystals (NCs). In this work, we have carried out a systematic study
      examining how the concentration of ligands (oleylamine and oleic acid) and the
      resulting acidity (or basicity) affects the hot-injection synthesis of CsPbBr3
      NCs. We devise a general synthesis scheme for cesium lead bromide NCs which
      allows control over size, size distribution, shape, and phase (CsPbBr3 or
      Cs4PbBr6) by combining key insights on the acid-base interactions that rule this
      ligand system. Furthermore, our findings shed light upon the solubility of PbBr2
      in this binary ligand system, and plausible mechanisms are suggested in order to
      understand the ligand-mediated phase control and structural stability of CsPbBr3
      NCs.

PMID- 29381327
TI  - Rapid Construction of Fe-Co-Ni Composition-Phase Map by Combinatorial Materials
      Chip Approach.
AB  - One hundred nanometer thick Fe-Co-Ni material chips were prepared and
      isothermally annealed at 500, 600, and 700  degrees C, respectively. Pixel-by
      pixel composition and structural mapping was performed by microbeam X-ray at
      synchrotron light source. Diffraction images were recorded at a rate of 1
      pattern/s. The XRD patterns were automatically processed, phase-identified, and
      categorized by hierarchical clustering algorithm to construct the composition
      phase map. The resulting maps are consistent with corresponding isothermal
      sections reported in the ASM Alloy Phase Diagram Database, verifying the
      effectiveness of the present approach in phase diagram construction.

PMID- 29381325
TI  - Smart Cell Culture Systems: Integration of Sensors and Actuators into
      Microphysiological Systems.
AB  - Technological advances in microfabrication techniques in combination with
      organotypic cell and tissue models have enabled the realization of
      microphysiological systems capable of recapitulating aspects of human physiology
      in vitro with great fidelity. Concurrently, a number of analysis techniques has
      been developed to probe and characterize these model systems. However, many
      assays are still performed off-line, which severely compromises the possibility
      of obtaining real-time information from the samples under examination, and which
      also limits the use of these platforms in high-throughput analysis. In this
      review, we focus on sensing and actuation schemes that have already been
      established or offer great potential to provide in situ detection or manipulation
      of relevant cell or tissue samples in microphysiological platforms. We will first
      describe methods that can be integrated in a straightforward way and that offer
      potential multiplexing and/or parallelization of sensing and actuation functions.
      These methods include electrical impedance spectroscopy, electrochemical
      biosensors, and the use of surface acoustic waves for manipulation and analysis
      of cells, tissue, and multicellular organisms. In the second part, we will
      describe two sensor approaches based on surface-plasmon resonance and mechanical
      resonators that have recently provided new characterization features for
      biological samples, although technological limitations for use in high-throughput
      applications still exist.

PMID- 29381328
TI  - Structural Polymorphism as the Result of Kinetically Controlled Self-Assembly.
AB  - Traditionally, the goal of self-assembly and supramolecular chemistry is to
      engineer an equilibrium structure with a desired geometry and functionality; this
      is achieved through careful choice of molecular monomers, growth conditions, and
      substrate. Supramolecular assemblies produced under nonequilibrium conditions, in
      contrast, can form metastable structures with conformations quite different from
      those accessible in equilibrium self-assembly. The study of nonequilibrium growth
      of clusters potentially impacts the study of nucleation in atmospheric aerosols,
      nucleation in organic crystallization, and mesoscale organization for systems
      ranging from biological molecules to molecular electronics. In our experiments,
      we prepare surface monolayers of small organic and organometallic molecules
      through direct injection of a solution onto a substrate in high vacuum. During
      this process, the rapid evaporation of small solution droplets in high vacuum can
      lead to nonequilibrium growth conditions. The resulting structures are then
      characterized by scanning tunneling microscopy. Among the features observed in
      these experiments are cyclic, hydrogen-bonded pentamers. For carboxylic acids,
      the two-molecule ring dimer is the common binding motif. Large, cyclic hydrogen
      bonded systems are uncommon, especially so for rings with five members. Despite
      this, pentagonal clusters appear to be a general phenomenon for systems
      containing adjacent strong and weak hydrogen-bonding elements on five-member
      aromatic rings. Regular pentamers have been observed as metastable structures for
      ferrocenecarboxylic acid, indole-2-carboxylic acid, and isatin (1-H-indole-2,3
      dione). Electronic structure calculations confirm the relative stability of these
      structures with respect to the dimer or catemer conformations which are observed
      in the solid-state crystal structures. For ferrocenecarboxylic acid, cyclic
      pentamers undergo further self-assembly, resulting in long-range order in
      conjunction with local 5-fold rotational symmetry. This system is the first
      reported self-assembled molecular quasicrystal, and it remains the only example
      of a hydrogen-bonded quasicrystal. This supramolecular structure forms as a
      result of the cocrystallization of hydrogen-bonded cyclic pentamers with
      intercalated molecular dimers. The shared bonding to a single dimer is
      responsible for locking the adjacent pentamers in specific distances and
      orientations, which produces the quasicrystal. Careful analysis of experimental
      data provides evidence that, in some cases, metastable clusters are formed in
      solution and then subsequently adsorb on the surface. This is a unusual mechanism
      for supramolecular assembly, and it has important implications for understanding
      questions in crystal growth, namely: what the initial stages of crystal growth
      are as molecules are first precipitating from solution; what role the solvent
      plays in determining crystal structure; and whether solvent-mediated clustering
      is important in the broader phenomenon of solid-state polymorphism.

PMID- 29381330
TI  - Metallosupramolecular Architectures Formed with Ferrocene-Linked Bis-Bidentate
      Ligands: Synthesis, Structures, and Electrochemical Studies.
AB  - The self-assembly of ligands of different geometries with metal ions gives rise
      to metallosupramolecular architectures of differing structural types. The
      rotational flexibility of ferrocene allows for conformational diversity, and, as
      such, self-assembly processes with 1,1'-disubstituted ferrocene ligands could
      lead to a variety of interesting architectures. Herein, we report a small family
      of three bis-bidentate 1,1'-disubstituted ferrocene ligands, functionalized with
      either 2,2'-bipyridine or 2-pyridyl-1,2,3-triazole chelating units. The self
      assembly of these ligands with the (usually) four-coordinate, diamagnetic metal
      ions Cu(I), Ag(I), and Pd(II) was examined using a range of techniques including
      1H and DOSY NMR spectroscopies, high-resolution electrospray ionization mass
      spectrometry, X-ray crystallography, and density functional theory calculations.
      Additionally, the electrochemical properties of these redox-active
      metallosupramolecular assemblies were examined using cyclic voltammetry and
      differential pulse voltammetry. The copper(I) complexes of the 1,1'-disubstituted
      ferrocene ligands were found to be coordination polymers, while the silver(I) and
      palladium(II) complexes formed discrete [1 + 1] or [2 + 2] metallomacrocyclic
      architectures.

PMID- 29381329
TI  - Fabrication of Hemin-Doped Serum Albumin-Based Fibrous Scaffolds for Neural
      Tissue Engineering Applications.
AB  - Neural tissue engineering (TE) represents a promising new avenue of therapy to
      support nerve recovery and regeneration. To recreate the complex environment in
      which neurons develop and mature, the ideal biomaterials for neural TE require a
      number of properties and capabilities including the appropriate biochemical and
      physical cues to adsorb and release specific growth factors. Here, we present
      neural TE constructs based on electrospun serum albumin (SA) fibrous scaffolds.
      We doped our SA scaffolds with an iron-containing porphyrin, hemin, to confer
      conductivity, and then functionalized them with different recombinant proteins
      and growth factors to ensure cell attachment and proliferation. We demonstrated
      the potential for these constructs combining topographical, biochemical, and
      electrical stimuli by testing them with clinically relevant neural populations
      derived from human induced pluripotent stem cells (hiPSCs). Our scaffolds could
      support the attachment, proliferation, and neuronal differentiation of hiPSC
      derived neural stem cells (NSCs), and were also able to incorporate active growth
      factors and release them over time, which modified the behavior of cultured cells
      and substituted the need for growth factor supplementation by media change.
      Electrical stimulation on the doped SA scaffold positively influenced the
      maturation of neuronal populations, with neurons exhibiting more branched
      neurites compared to controls. Through promotion of cell proliferation,
      differentiation, and neurite branching of hiPSC-derived NSCs, these conductive SA
      fibrous scaffolds are of broad application in nerve regeneration strategies.

PMID- 29381331
TI  - Determining the Physical Properties of Molecules with Nanometer-Scale Pores.
AB  - Nanometer-scale pores have been developed for the detection, characterization,
      and quantification of a wide range of analytes (e.g., ions, polymers, proteins,
      anthrax toxins, neurotransmitters, and synthetic nanoparticles) and for DNA
      sequencing. We describe the key requirements that made this method possible and
      how the technique evolved. Finally, we show that, despite sound theoretical work,
      which advanced both the conceptual framework and quantitative capability of the
      method, there are still unresolved questions that need to be addressed to further
      improve the technique.

PMID- 29381332
TI  - Structural and Biochemical Studies of Substrate Selectivity in Ascaris suum
      Thiolases.
AB  - Thiolases are a class of carbon-carbon bond forming enzymes with important
      applications in biotechnology and metabolic engineering as they provide a general
      method for the condensation of two acyl coenzyme A (CoA) substrates. As such,
      developing a greater understanding of their substrate selectivity would expand
      our ability to engineer the enzymatic or microbial production of a broad range of
      small-molecule targets. Here, we report the crystal structures and biochemical
      characterization of Acat2 and Acat5, two biosynthetic thiolases from Ascaris suum
      with varying selectivity toward branched compared to linear compounds. The
      structure of the Acat2-C91S mutant bound to propionyl-CoA shows that the terminal
      methyl group of the substrate, representing the alpha-branch point, is directed
      toward the conserved Phe 288 and Met 158 residues. In Acat5, the Phe ring is
      rotated to accommodate a hydroxyl-pi interaction with an adjacent Thr side chain,
      decreasing space in the binding pocket and possibly accounting for its strong
      preference for linear substrates compared to Acat2. Comparison of the different
      Acat thiolase structures shows that Met 158 is flexible, adopting alternate
      conformations with the side chain rotated toward or away from a covering loop at
      the back of the active site. Mutagenesis of residues in the covering loop in
      Acat5 with the corresponding residues from Acat2 allows for highly increased
      accommodation of branched substrates, whereas the converse mutations do not
      significantly affect Acat2 substrate selectivity. Our results suggest an
      important contribution of second-shell residues to thiolase substrate selectivity
      and offer insights into engineering this enzyme class.

PMID- 29381334
TI  - 3-Carboxybenzoboroxole Functionalized Polyethylenimine Modified Magnetic Graphene
      Oxide Nanocomposites for Human Plasma Glycoproteins Enrichment under
      Physiological Conditions.
AB  - Boronate affinity materials have been successfully used for the selective
      recognition of glycoproteins. However, by such materials, the large-scale
      glycoproteins enrichment from human plasma under physiological conditions is
      rarely reported. In this work, 3-carboxybenzoboroxole (CBX) functionalized
      polyethylenimine (PEI) modified magnetic graphene oxide nanocomposites were
      synthesized. Benefitting from the low pKa value of CBX (~6.9) and PEI dendrimer
      assisted multivalent binding, the Freundlich constant (KF) for the adsorption of
      horseradish peroxidase (HRP) was 3.0-7.3 times higher than that obtained by
      previous work, displaying the high enrichment capacity. Moreover, PEI could
      improve the hydrophilicity of nanocomposites and reduce nonglycoprotein
      adsorption. Therefore, such nanocomposites were successfully applied to the
      analysis of human plasma glycoproteome under physiological conditions, and the
      identified glycoproteins number and recognition selectivity was increased when
      compared to the results obtained by previous boronic acid-functionalized
      particles (Sil@Poly(APBA-co-MBAAm)) under common alkaline condition (137 vs 78
      and 67.8% vs 57.8%, respectively). In addition, thrombin (F2), an important
      plasma glycoprotein, labile under alkaline conditions, was specifically
      identified by our method, demonstrating the great promise of such nanocomposites
      in the deep-coverage glycoproteome analysis.

PMID- 29381333
TI  - Highly Efficient Exosome Isolation and Protein Analysis by an Integrated
      Nanomaterial-Based Platform.
AB  - Exosomes play important roles in mediating intercellular communication and
      regulating a variety of biological processes, but clear understanding of their
      functions and biogenesis has not been achieved, due to the high technical
      difficulties involved in analysis of small vesicular structures that contain a
      high proportion of membrane structures. Herein, we designed a novel approach to
      integrate two nanomaterials carrying varied surface properties, the hydrophilic,
      macroporous graphene foam (GF) and the amphiphilic periodic mesoporous
      organosilica (PMO), for efficient exosome isolation from human serum and
      effective protein profiling. The high specific surface area of GF, after
      modification with the antibody against the exosomal protein marker, CD63, allowed
      highly specific isolation of exosomes from complex biological samples with high
      recovery. Since the organic solvent, methanol, turned out to be the most
      effective lysis solution for releasing the exosomal proteins, the amphiphilic PMO
      was employed to rapidly recover the exosomal proteins, including the highly
      hydrophobic membrane proteins. The fine pores of PMO also acted as the
      nanoreactors to accelerate protein digestion that produced peptides subject to
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A total of
      334 proteins with 111 membrane proteins [31% of these contained >2 transmembrane
      domains (TMD)] were identified using the integrated GF/PMO platform. In contrast,
      with the commercial exosome isolation kit and the in-solution protein digestion
      method, only 151 proteins were found, with 28 being membrane proteins (only one
      contained three TMDs). Our results support that the integrated GF/PMO platform is
      of great value to facilitate the comprehensive characterization of exosomal
      proteins for better understanding of their functions and for identification of
      more exosome-based disease markers.

PMID- 29381336
TI  - Theoretical Prediction of Robust Second-Row Oxyanion Clusters in the Metastable
      Domain of Antielectrostatic Hydrogen Bonding.
AB  - We provide ab initio and density functional theory evidence for a family of
      surprisingly robust like-charged clusters of common HSO4- and H2PO4- oxyanions,
      ranging up to tetramers of net charge 4-. Our results support other recent
      theoretical and experimental evidence for "antielectrostatic" hydrogen-bonded
      (AEHB) species that challenge conventional electrostatic conceptions and force
      field modeling of closed-shell ion interactions. We provide structural and
      energetic descriptors of the predicted kinetic well-depths (in the range 3-10
      kcal/mol) and barrier widths (in the range 2-4 A) for simple AEHB dimers,
      including evidence of extremely strong hydrogen bonding in the fluoride-bisulfate
      dianion. For more complex polyanionic species, we employ natural-bond-orbital
      based descriptors to characterize the electronic features of the cooperative
      hydrogen-bonding network that are able to successfully defy Coulomb explosion.
      The computational results suggest a variety of kinetically stable AEHB species
      that may be suitable for experimental detection as long-lived gas-phase species
      or structural units of condensed phases, despite the imposing electrostatic
      barriers that oppose their formation under ambient conditions.

PMID- 29381335
TI  - Macromolecular pHPMA-Based Nanoparticles with Cholesterol for Solid Tumor
      Targeting: Behavior in HSA Protein Environment.
AB  - Nanoparticles (NPs) that form by self-assembly of amphiphilic poly(N-(2
      hydroxypropyl)-methacrylamide) (pHPMA) copolymers bearing cholesterol side groups
      are potential drug carriers for solid tumor treatment. Here, we investigate their
      behavior in solutions of human serum albumin (HSA) in phosphate buffered saline.
      Mixed solutions of NPs, from polymer conjugates with or without the anticancer
      drug doxorubicin (Dox) bound to them, and HSA at concentrations up to the
      physiological value are characterized by synchrotron small-angle X-ray scattering
      and isothermal titration calorimetry. When Dox is absent, a small amount of HSA
      molecules bind to the cholesterol groups that form the core of the NPs by
      diffusing through the loose pHPMA shell or get caught in meshes formed by the
      pHPMA chains. These interactions are strongly hindered by the presence of Dox,
      which is distributed in the pHPMA shell, meaning that the delivery of Dox by the
      NPs in the human body is not affected by the presence of HSA.

PMID- 29381337
TI  - Photothermal Effect-Triggered Drug Release from Hydrogen Bonding-Enhanced
      Polymeric Micelles.
AB  - Incorporation of noncovalent interactions into hydrophobic cores of polymeric
      micelles provides the micelles with enhanced physical stability and drug loading
      efficiency, however, it also creates obstacles for drug release due to the strong
      interactions between carriers and drugs. Herein, a series of amphiphilic block
      copolymers based on poly(ethylene glycol)- b-poly(l-lysine) (mPEG- b-PLL) with
      similar chemical structures, while different hydrogen bonding donors (urethane,
      urea, and thiourea groups) are synthesized, and their capacities for codelivery
      of anticancer drug (e.g., doxorubicin) and photothermal agent (e.g., indocyanine
      green) are investigated. The resulting hybrid micelles display decreased critical
      micelle concentrations (CMCs) and enhanced micelle stabilities due to the
      hydrogen bonding between urea groups in the polymers. Moreover, the strong
      hydrogen bonds between the urea/thiourea groups and drugs provide the carriers
      with enhanced drug loading efficiencies, decreased micelle sizes, however, slower
      drug release profiles as well. When exposed to the near-infrared laser
      irradiation, destabilization of the hydrogen bonding through photothermal effect
      triggers fast and controlled drug releases from the micelles, which dramatically
      promotes the aggregation of the drugs in the nuclei, resulting in an enhanced
      anticancer activity. These results demonstrate that the hydrogen bonding-enhanced
      micelles are promising carriers for controllable chemo-photothermal synergistic
      therapy.

PMID- 29381338
TI  - Influence of Pressure on the Composition of Gaseous Reference Materials.
AB  - We have shown that the amount fraction of carbon dioxide in a nitrogen or
      synthetic air matrix stored in cylinders increases as the pressure of the gas
      mixture reduces, while the amount fraction of methane remains unchanged. Our
      measurements show the initial amount fraction of carbon dioxide to be lower than
      the gravimetric value after preparation, which we attribute to the adsorption of
      a proportion of the molecules to active sites on the internal surface of the
      cylinder and the valve. As the mixture is consumed, the pressure in the cylinder
      reduces and the amount fraction of the component is observed to increase. The
      effect is less pronounced in the presence of water vapor. More dramatic effects
      have been observed for hydrogen chloride. These findings have significant
      implications for the preparation of high accuracy gaseous reference materials
      with unprecedented uncertainties which underpin a broad range of requirements, in
      particular atmospheric monitoring of high impact greenhouse gases.

PMID- 29381340
TI  - Synthesis, Characterization, and Optoelectronic Properties of Iridium Complexes
      Bearing Nonconjugated Six-Membered Chelating Ligands.
AB  - We report the synthesis, characterization, and optoelectronic properties of a
      series of four new luminescent iridium(III) complexes, 1-4, of the form
      [Ir(C?N)2(N?N)]PF6 (where C?N is the nonconjugated benzylpyridinato (bnpy) and
      N?N is a neutral diimine ancillary ligand) with the goal of investigating the
      effect of the methylene spacer between the coordination moieties of the C?N
      ligand on the optoelectronic properties of the complexes. The crystal structures
      of 1-3 illustrate two possible orientations of the methylene unit of the bnpy
      ligand. The formation of these two separate conformers is a result of the
      conformational flexibility of the bnpy ligand. In complexes 3 and 4, mixtures of
      the two conformers were observed by 1H NMR spectroscopy in CDCl3 at room
      temperature, whereas only a single conformer is detected for 1 and 2. Detailed
      DFT calculations corroborate NMR experiments, accounting for the presence and
      relative populations of the two conformers. The optoelectronic properties of all
      four complexes, rationalized by the theoretical study, demonstrate that the
      interruption of conjugation in the C?N ligands results in a reduced
      electrochemical gap but similar triplet state energies and lower
      photoluminescence quantum yields in comparison to the reference complexes R1-R4.
      Depending on the nature of the N?N ligand, we observe (1) marked variations of
      the ratio of the conformers at ambient temperature and (2) phosphorescence
      ranging from yellow to red.

PMID- 29381341
TI  - The Role of Alkoxide Initiator, Spin State, and Oxidation State in Ring-Opening
      Polymerization of epsilon-Caprolactone Catalyzed by Iron Bis(imino)pyridine
      Complexes.
AB  - Density functional theory (DFT) is employed to characterize in detail the
      mechanism for the ring-opening polymerization (ROP) of epsilon-caprolactone
      catalyzed by iron alkoxide complexes bearing redox-active bis(imino)pyridine
      ligands. The combination of iron with the non-innocent bis(imino)pyridine ligand
      permits comparison of catalytic activity as a function of oxidation state (and
      overall spin state). The reactivities of aryl oxide versus alkoxide initiators
      for the ROP of epsilon-caprolactone are also examined. An experimental test of a
      computational prediction reveals an Fe(III) bis(imino)pyridine bis-neopentoxide
      complex to be competent for ROP of epsilon-caprolactone.

PMID- 29381339
TI  - Structure and Enzymatic Properties of an Unusual Cysteine Tryptophylquinone
      Dependent Glycine Oxidase from Pseudoalteromonas luteoviolacea.
AB  - Glycine oxidase from Pseudoalteromonas luteoviolacea (PlGoxA) is a cysteine
      tryptophylquinone (CTQ)-dependent enzyme. Sequence analysis and phylogenetic
      analysis place it in a newly designated subgroup (group IID) of a recently
      identified family of LodA-like proteins, which are predicted to possess CTQ. The
      crystal structure of PlGoxA reveals that it is a homotetramer. It possesses an N
      terminal domain with no close structural homologues in the Protein Data Bank. The
      active site is quite small because of intersubunit interactions, which may
      account for the observed cooperativy toward glycine. Steady-state kinetic
      analysis yielded the following values: kcat = 6.0 +/- 0.2 s-1, K0.5 = 187 +/- 18
      MUM, and h = 1.77 +/- 0.27. In contrast to other quinoprotein amine
      dehydrogenases and oxidases that exhibit anomalously large primary kinetic
      isotope effects on the rate of reduction of the quinone cofactor by the amine
      substrate, no significant primary kinetic isotope effect was observed for this
      reaction of PlGoxA. The absorbance spectrum of glycine-reduced PlGoxA exhibits
      features in the range of 400-650 nm that have not previously been seen in other
      quinoproteins. Thus, in addition to the unusual structural features of PlGoxA,
      the kinetic and chemical reaction mechanisms of the reductive half-reaction of
      PlGoxA appear to be distinct from those of other amine dehydrogenases and amine
      oxidases that use tryptophylquinone and tyrosylquinone cofactors.

PMID- 29381342
TI  - High-Throughput Analysis for Artemisinins with Deep Eutectic Solvents
      Mechanochemical Extraction and Direct Analysis in Real Time Mass Spectrometry.
AB  - A fast, simple, efficient, and high-throughput analytical protocol using deep
      eutectic solvents (DES) for mechanochemical extraction (MCE) combined with direct
      analysis in real time mass spectrometry (DART-MS) was developed to quantify heat
      labile bioactive compounds artemisinin (AN), arteannuin B, and artemisinic acid
      from Aretemisia annua. MCE is performed at room temperature, and target analytes
      are released into DESs within seconds; this method demonstrated multiple
      advantages over traditional extraction methods and organic solvents. DART-MS was
      then used for the structure confirmation and quantification for the three
      artemisinin major components extracted from plants of five locations. Liquid
      chromatography (LC) measurements were performed as well for results verification
      and comparison, and the amounts obtained were consistent between the two
      techniques. DART-MS showed advantages in simplicity, low limit of detection (5-15
      ng mL-1), and superior speed (10-20 s), but with slightly higher relative
      standard deviation (0.7-10.8%). The entire protocol can be accomplished in a few
      minutes from raw materials to quantitative results. This study aims to establish
      a methodology combining high-efficiency sample pretreatment and rapid chemical
      analysis from complex matrixes, where the time-consuming separation procedure can
      be eliminated. Additionally, the use of toxic organic solvents needed in the
      process of chemical extraction and analysis is largely avoided. In general, this
      investigation provides a robust analytical procedure that can be widely used in
      many areas of research and industrial activities.

PMID- 29381343
TI  - Gold Nanofilms at Liquid-Liquid Interfaces: An Emerging Platform for Redox
      Electrocatalysis, Nanoplasmonic Sensors, and Electrovariable Optics.
AB  - The functionality of liquid-liquid interfaces formed between two immiscible
      electrolyte solutions (ITIES) can be markedly enhanced by modification with
      supramolecular assemblies or solid nanomaterials. The focus of this Review is
      recent progress involving ITIES modified with floating assemblies of gold
      nanoparticles or "nanofilms". Experimental methods to controllably modify liquid
      liquid interfaces with gold nanofilms are detailed. Also, we outline an array of
      techniques to characterize these gold nanofilms in terms of their physiochemical
      properties (such as reflectivity, conductivity, catalytic activity, or plasmonic
      properties) and physical interfacial properties (for example, interparticle
      spacing and immersion depth at the interface). The ability of floating gold
      nanofilms to impact a diverse range of fields is demonstrated: in particular,
      redox electrocatalysis, surface-enhanced Raman spectroscopy (SERS) or surface
      plasmon resonance (SPR) based sensors, and electrovariable optical devices.
      Finally, perspectives on applications beyond the state-of-the-art are provided.

PMID- 29381344
TI  - Structural Analysis of Polysaccharide Networks by Transmission Electron
      Microscopy: Comparison with Small-Angle X-ray Scattering.
AB  - Polysaccharide gels assembled from the anionic biopolymers pectin and carrageenan
      have been studied using transmission electron microscopy (TEM). Gels were formed
      in several different ways: for pectin, hydrogen bonding was used to form junction
      zones between strands, whereas for carrageenan systems, several different ion
      types were used to form ionotropic networks. Using this approach, several
      distinct network architectures were realized. In addition to preparing gelled
      samples for electron microscopy, a set of samples was taken without performing
      the additional treatment necessitated by the TEM measurements, and these were
      studied directly by small-angle X-ray scattering (SAXS). Taking careful
      consideration of the relative merits of different image sizes and available
      processing techniques, the real-space images acquired by TEM were used via radial
      integration of the Fourier transform to produce simulated scattering patterns.
      These intensity-versus-wavevector plots were compared with the results of SAXS
      experiments carried out on the unadulterated gels using synchrotron radiation.
      Although information regarding chain thicknesses and flexibilities was found to
      be modified by labeling and changes in the dielectric constant and mechanical
      properties of the surroundings in the TEM, the studies carried out here show that
      careful protocols can produce data sets where information acquired above ~20 nm
      is broadly consistent with that obtained by SAXS studies carried out on
      unadulterated samples. The fact that at larger length scale the structure of
      these water-rich networks seems largely preserved in the TEM samples suggests
      that three-dimensional (3D) TEM tomography experiments carried out with careful
      sample preparation will be valuable tools for measuring network architecture and
      connectivity; information that is lost in SAXS owing to the intrinsic averaging
      nature of the technique.

PMID- 29381345
TI  - Chemical Phenomena of Atomic Force Microscopy Scanning.
AB  - Atomic force microscopy is widely used for nanoscale characterization of
      materials by scientists worldwide. The long-held belief of ambient AFM is that
      the tip is generally chemically inert but can be functionalized with respect to
      the studied sample. This implies that basic imaging and scanning procedures do
      not affect surface and bulk chemistry of the studied sample. However, an in-depth
      study of the confined chemical processes taking place at the tip-surface junction
      and the associated chemical changes to the material surface have been missing as
      of now. Here, we used a hybrid system that combines time-of-flight secondary ion
      mass spectrometry with an atomic force microscopy to investigate the chemical
      interactions that take place at the tip-surface junction. Investigations showed
      that even basic contact mode AFM scanning is able to modify the surface of the
      studied sample. In particular, we found that the silicone oils deposited from the
      AFM tip into the scanned regions and spread to distances exceeding 15 MUm from
      the tip. These oils were determined to come from standard gel boxes used for the
      storage of the tips. The explored phenomena are important for interpreting and
      understanding results of AFM mechanical and electrical studies relying on the
      state of the tip-surface junction.

PMID- 29381346
TI  - Mimic Carbonic Anhydrase Using Metal-Organic Frameworks for CO2 Capture and
      Conversion.
AB  - Carbonic anhydrase (CA) is a zinc-containing metalloprotein, in which the Zn
      active center plays the key role to transform CO2 into carbonate. Inspired by
      nature, herein we used metal-organic frameworks (MOFs) to mimic CA for CO2
      conversion, on the basis of the structural similarity between the Zn coordination
      in MOFs and CA active center. The biomimetic activity of MOFs was investigated by
      detecting the hydrolysis of para-nitrophenyl acetate, which is a model reaction
      used to evaluate CA activity. The biomimetic materials (e.g., CFA-1) showed good
      catalytic activity, and excellent reusability, and solvent and thermal stability,
      which is very important for practical applications. In addition, ZIF-100 and CFA
      1 were used to mimic CA to convert CO2 gas, and exhibited good efficiency on CO2
      conversion compared with those of other porous materials (e.g., MCM-41, active
      carbon). This biomimetic study revealed a novel CO2 treatment method. Instead of
      simply using MOFs to absorb CO2, ZIF-100 and CFA-1 were used to mimic CA for in
      situ CO2 conversion, which provides a new prospect in the biological and
      industrial applications of MOFs.

PMID- 29381347
TI  - Impacts of the Degradation of 2,3,3,3-Tetrafluoropropene into Trifluoroacetic
      Acid from Its Application in Automobile Air Conditioners in China, the United
      States, and Europe.
AB  - HFO-1234yf (2,3,3,3-tetrafluoropropene) was proposed as an automobile air
      conditioner (MAC) refrigerant worldwide. However, its atmospheric degradation
      product is the highly soluble and phytotoxic trifluoroacetic acid (TFA), which
      persists in aquatic environments. We used a global three-dimensional chemical
      transport model to assess the potential environmental effects resulting from
      complete future conversion of the refrigerant in all MAC to HFO-1234yf in China,
      the United States, and Europe. The annual mean atmospheric concentrations of HFO
      1234yf were 2.62, 2.20, and 2.73 pptv, and the mean deposition rates of TFA were
      0.96, 0.45, and 0.52 kg km-2 yr-1, in three regions. The regional TFA deposition
      sources mainly came from emissions within the same region. The annual TFA
      deposition in the North Pole region was lower than the global average and mainly
      originated from European emissions. A potential doubling in the future HFO-1234yf
      emissions in China mainly affected the local TFA depositions. The TFA
      concentrations in rainwater were strongly affected by the regional precipitation
      rates. North Africa and the Middle East, regions with scant rainfall, had
      extremely high TFA concentrations. The rainwater concentrations of TFA during
      individual rain events can exceed the level considered to be safe, indicating
      substantial potential regional risks from future HFO-1234yf use.

PMID- 29381348
TI  - Disordered Nanostructure in Huntingtin Interacting Protein K Acts as a
      Stabilizing Switch To Prevent Protein Aggregation.
AB  - Protein misfolding due to mutation(s) and/or generation of unstable intermediate
      state(s) can be the cause of aberrant aggregations, leading to cellular
      degeneration. While molecular signatures like amyloidogenic regions cause
      aggregation, other features in proteins, like disorder and unique complexity
      regions, regulate and restrict such adhesive accumulation processes. Huntingtin
      interacting protein K (HYPK) is an aggregation-prone protein. Using various
      biophysical, microscopy, and computational techniques, we have deciphered how
      HYPK's N-terminal nanodisordered region plays a significant modulatory role in
      preventing its own aggregation and that of other proteins. HYPK's C-terminal
      hydrophobic regions lead to annular oligomerization and intermolecular charge
      interactions among the residues of low-complexity region (LCR) generate amorphous
      aggregates. The N-terminal disordered nanostructure loops toward the C-terminus,
      and a negative charge-rich patch in this region interacts with the LCR to shield
      LCR's positive charges. This interaction is required to prevent HYPK aggregation.
      Loss of this interaction causes partial unfolding of the structured C-terminus,
      resulting in HYPK's molten globule-like state and rapid annular oligomerization.
      The N-terminus also determines the specificity to mediate the differential
      bindings with aggregation-prone and wild type Huntingtin-exon1 proteins
      (Huntingtin97Q-exon1 and Huntingtin25Q-exon1). A sliding interaction of the
      specific N-terminal segment of HYPK along the extended polyglutamine region of
      Huntingtin-exon1 is responsible for HYPK's higher affinity for aggregation-prone
      Huntingtin than for its non-aggregating counterpart. Overall, our study provides
      evidence of the existence of disordered nanostructure in HYPK protein that
      mechanistically plays a decisive role in preventing both self and non-self
      protein aggregation.

PMID- 29381349
TI  - Phosphinidene-Bridged MoMn Derivatives of the Thiophosphinidene Complex
      [Mo2Cp2(MU-kappa2:kappa1,eta6-SPMes*)(CO)2] (Mes* = 2,4,6-C6H2tBu3).
AB  - The title complex (1) reacted with [Mn2(CO)10] under visible-UV irradiation
      (toluene solution and quartz glassware) to give a mixture of the phosphinidene
      complex [MnMoCp(MU-kappa1:kappa1,eta6-PMes*)(CO)4], the cluster [Mn2Mo2Cp2(MU
      kappa1:kappa1,eta6-PMes*)(MU3-S)(CO)8], and the thiophosphinidene complex
      [MnMoCp(MU-kappa2:kappa1,eta4-SPMes*)(CO)5], in yields of ca. 60, 20, and 10%
      respectively (Mes* = 2,4,6-C6H2tBu3). The major product follows from formal
      replacement of the SMoCp(CO)2 fragment in 1 with a Mn(CO)4 fragment, and
      displayed multiple bonding to phosphorus (Mn-P = 2.1414(8) A); the tetranuclear
      cluster results from formal insertion of a Mn2(CO)6 fragment in 1, with cleavage
      of P-S and P-Mo bonds, to render a MU3-S bridged Mn2Mo core bearing an exocyclic
      phosphinidene ligand involved in multiple bonding to one of the Mn atoms (Mn-P =
      2.140(2) A); the thiophosphinidene complex (Mn-P = 2.294(1) A) formally results
      from addition of sulfur and carbon monoxide to the major MnMo product, a
      transformation which actually could be performed stepwise, via the MnMo
      thiophosphinidene complex [MnMoCp(MU-kappa2:kappa1,eta6-SPMes*)(CO)4]. When the
      photolysis of 1 and [Mn2(CO)10] was performed in tetrahydrofuran solution and
      using conventional glassware, then the V-shaped cluster [Mn2MoCp{MU
      kappa1:kappa1:kappa1,eta5-P(C6H3tBu3)}(CO)8] was obtained selectively (Mo-Mn =
      3.2910(5) A, Mn-Mn = 2.9223(5) A), which unexpectedly displays a
      cyclohexadienylidene-phosphinidene ligand resulting from H atom abstraction at
      the aryl ring of the precursor. Density functional theory calculations on the
      complexes [LnM(MU-kappa1:kappa1,eta6-PMes*)MoCp] (MLn = MoCp(CO)2, Mn(CO)4,
      Co(CO)3) revealed that the degree of delocalization of the metal-phosphorus pi
      bonding interaction over the Mo-P-M chain is significantly conditioned by the
      heterometal fragment MLn, it being increased in the order Mn <= Mo < Co.

PMID- 29381350
TI  - Scalable Access to Arylomycins via C-H Functionalization Logic.
AB  - Arylomycins are a promising class of "latent" antibacterial natural products
      currently in preclinical development. Access to analogues within this family has
      previously required a lengthy route involving multiple functional group
      manipulations that is costly and time-intensive on scale. This study presents a
      simplified route predicated on simple C-H functionalization logic that is enabled
      by a Cu-mediated oxidative phenol coupling that mimics the putative biosynthesis.
      This operationally simple macrocyclization is the largest of its kind and can be
      easily performed on gram scale. The application of this new route to a formal
      synthesis of the natural product and a collection of new analogues along with
      their biological evaluation is also reported.

PMID- 29381351
TI  - Ir/Cu Dual Catalysis: Enantio- and Diastereodivergent Access to alpha,alpha
      Disubstituted alpha-Amino Acids Bearing Vicinal Stereocenters.
AB  - We describe a fully stereodivergent synthesis of a range of alpha,alpha
      disubstituted alpha-amino acids via an Ir/Cu-catalyzed alpha-allylation of
      readily available imine esters. The introduction of a Cu-Phox complex-activated
      imine ester into the chiral iridium-catalyzed allylic allylation process is
      crucial for its high reactivity and excellent enantio- and diastereoselectivity
      (up to >99% ee and >20:1 dr). Importantly, the two chiral catalysts allow for
      full control over the configuration of the stereocenters, affording all
      stereoisomers of the desired products. The utility of this methodology was
      demonstrated by synthesizing dipeptides and analogues of bioactive molecules in a
      stereodivergent manner.

PMID- 29381353
TI  - Colorimetric Detection of Norovirus in Oyster Samples through DNAzyme as a
      Signaling Probe.
AB  - Worldwide, norovirus is one of the most associated causes of acute
      gastroenteritis, which leads to nearly 50 000 child deaths every year in
      developing countries. Therefore, there is great demand to develop a rapid, low
      cost, and accurate detection assay for the foodborne norovirus infection to
      reduce mortality caused by norovirus. Considering the importance of norovirus, we
      have demonstrated a highly sensitive and specific colorimetric detection method
      for analysis of human norovirus genogroups I and II (HuNoV GI and GII) in oyster
      samples. This is the first report to employ colorimetric HRPzyme-integrated
      polymerase chain reaction (PCR) for direct norovirus detection from the real
      shellfish samples. We found that the HRPzyme-integrated PCR method is more
      sensitive than the gel electrophoresis approach and could detect the HuNoV GI and
      GII genome up to 1 copy/mL. The specificity of the proposed method was
      successfully demonstrated for HuNoV GI and GII. Further, we performed testing
      HuNoVs in the spiked oyster samples, and the HRPzyme-integrated PCR method proved
      to be an ultrasensitive and selective method for detecting HuNoVs in the real
      samples. By integration of the proposed method with the portable PCR machine, it
      would be more reliable to improve food safety by detecting HuNoVs in the
      different types of shellfish, such as oyster and mussel, at the production field.

PMID- 29381354
TI  - A Predictive Model for the Decarboxylation of Silver Benzoate Complexes Relevant
      to Decarboxylative Coupling Reactions.
AB  - Decarboxylative coupling reactions offer an attractive route to generate
      functionalized arenes from simple and readily available carboxylic acid coupling
      partners, yet they are underutilized due to limitations in the scope of
      carboxylic acid coupling partner. Here we report that the field effect parameter
      (F) has a substantial influence on the rate of decarboxylation of well-defined
      silver benzoate complexes. This finding provides the opportunity to surpass
      current substrate limitations associated with decarboxylation and to enable
      widespread utilization of decarboxylative coupling reactions.

PMID- 29381352
TI  - Design and Mechanism of (S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1
      carboxylic Acid, a Highly Potent gamma-Aminobutyric Acid Aminotransferase
      Inactivator for the Treatment of Addiction.
AB  - gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the
      central nervous system. Inhibition of GABA aminotransferase (GABA-AT), a
      pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, has been
      established as a possible strategy for the treatment of substance abuse. The
      raised GABA levels that occur as a consequence of this inhibition have been found
      to antagonize the rapid release of dopamine in the ventral striatum (nucleus
      accumbens) that follows an acute challenge by an addictive substance. In
      addition, increased GABA levels are also known to elicit an anticonvulsant effect
      in patients with epilepsy. We previously designed the mechanism-based inactivator
      (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (2), now called CPP
      115, that is 186 times more efficient in inactivating GABA-AT than vigabatrin,
      the only FDA-approved drug that is an inactivator of GABA-AT. CPP-115 was found
      to have high therapeutic potential for the treatment of cocaine addiction and for
      a variety of epilepsies, has successfully completed a Phase I safety clinical
      trial, and was found to be effective in the treatment of infantile spasms (West
      syndrome). Herein we report the design, using molecular dynamics simulations,
      synthesis, and biological evaluation of a new mechanism-based inactivator, (S)-3
      amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (5), which was
      found to be almost 10 times more efficient as an inactivator of GABA-AT than CPP
      115. We also present the unexpected crystal structure of 5 bound to GABA-AT, as
      well as computational analyses used to assist the structure elucidation process.
      Furthermore, 5 was found to have favorable pharmacokinetic properties and low off
      target activities. In vivo studies in freely moving rats showed that 5 was
      dramatically superior to CPP-115 in suppressing the release of dopamine in the
      corpus striatum, which occurs subsequent to either an acute cocaine or nicotine
      challenge. Compound 5 also attenuated increased metabolic demands (neuronal
      glucose metabolism) in the hippocampus, a brain region that encodes spatial
      information concerning the environment in which an animal receives a reinforcing
      or aversive drug. This multidisciplinary computational design to preclinical
      efficacy approach should be applicable to the design and improvement of mechanism
      based inhibitors of other enzymes whose crystal structures and inactivation
      mechanisms are known.

PMID- 29381355
TI  - Ribocyclophanes A-E, Glycosylated Cyclophanes with Antiproliferative Activity
      from Two Cultured Terrestrial Cyanobacteria.
AB  - The cell extracts of two cultured freshwater Nostoc spp., UIC 10279 and UIC
      10366, both from the suburbs of Chicago, showed antiproliferative activity
      against MDA-MB-231 and MDA-MB-435 cancer cell lines. Bioassay-guided
      fractionation led to the isolation of five glycosylated cylindrocyclophanes,
      named ribocyclophanes A-E (1-5) and cylindrocyclophane D (6). The structure
      determination was carried out by HRESIMS and 1D and 2D NMR analyses and confirmed
      by single-crystal X-ray crystallography. The structures of ribocyclophanes A-E (1
      5) contain a beta-d-ribopyranose glycone in the rare 1 C4 conformation. Among
      isolated compounds, ribocyclophane D (4) showed antiproliferative activity
      against MDA-MB-435 and MDA-MB-231 cancer cells with an IC50 value of less than 1
      MUM.

PMID- 29381357
TI  - Anti-Staphylococcal Calopins from Fruiting Bodies of Caloboletus radicans.
AB  - Three new and seven known calopins were isolated from Caloboletus radicans. The
      structures of the new cyclocalopins, 8-deacetylcyclocalopin B (1), cyclocalopin A
      15-ol (2), and 12,15-dimethoxycyclocalopin A (3), were mainly elucidated by NMR
      and MS data analysis. The stereochemistry of 1-3 was assigned based on NOE
      correlations and coupling constants and by comparison of their CD spectra with
      those of similar known calopins. While 1-10 were inactive against two cancer cell
      lines, they displayed anti-staphylococcal activity against methicillin-resistant
      Staphylococcus aureus strains (MRSA) with MIC values of 16-256 MUg/mL. Moreover,
      some calopins were active against the fish pathogen Enterococcus faecalis F1B1.

PMID- 29381356
TI  - Astaxanthin Induces the Nrf2/HO-1 Antioxidant Pathway in Human Umbilical Vein
      Endothelial Cells by Generating Trace Amounts of ROS.
AB  - Astaxanthin is a powerful antioxidant that possesses potent protective effects
      against various human diseases and physiological disorders. However, the
      mechanisms underlying its antioxidant functions in cells are not fully
      understood. In the present study, the effects of astaxanthin on reactive oxygen
      species (ROS) production and antioxidant enzyme activity, as well as mitogen
      activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K)/Akt, and
      the nuclear factor erythroid 2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1)
      pathways in human umbilical vein endothelial cells (HUVECs), were examined. It
      was shown that astaxanthin (0.1, 1, and 10 MUM) induced ROS production by 9.35%,
      14.8%, and 18.06% compared to control, respectively, in HUVECs. In addition,
      astaxanthin increased the mRNA levels of phase II enzymes HO-1 and also promoted
      GSH-Px enzyme activity. Furthermore, we observed ERK phosphorylation, nuclear
      translocation of Nrf-2, and activation of antioxidant response element-driven
      luciferase activity upon astaxanthin treatment. Knockdown of Nrf-2 by small
      interfering RNA inhibited HO-1 mRNA expression by 60%, indicating that the Nrf
      2/ARE signaling pathway is activated by astaxanthin. Our results suggest that
      astaxanthin activates the Nrf-2/HO-1 antioxidant pathway by generating small
      amounts of ROS.

PMID- 29381358
TI  - 3-((R)-4-(((R)-6-(2-Bromo-4-fluorophenyl)-5-(ethoxycarbonyl)-2-(thiazol-2-yl)-3,6
      dihydropyrimidin-4-yl)methyl)morpholin-2-yl)propanoic Acid (HEC72702), a Novel
      Hepatitis B Virus Capsid Inhibitor Based on Clinical Candidate GLS4.
AB  - The inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for
      the development of chronic hepatitis B (CHB) therapeutics. On the basis of the
      preclinical properties and clinical results of GLS4, we carried out further
      investigation to seek a better candidate compound with appropriate anti-HBV
      potency, reduced hERG activity, decreased CYP enzyme induction, and improved
      pharmacokinetic (PK) properties. To this end, we have successfully found that
      morpholine carboxyl analogues with comparable anti-HBV activities to that of GLS4
      showed decreased hERG activities, but they displayed strong CYP3A4 induction in a
      concentration-dependent manner, except for morpholine propionic acid analogues.
      After several rounds of modification, compound 58 (HEC72702), which had an (R)
      morpholine-2-propionic acid at the C6 position of its dihydropyrimidine core
      ring, was found to display no induction of the CYP1A2, CYP3A4, or CYP2B6 enzyme
      at the high concentration of 10 MUM. In particular, it demonstrated a good
      systemic exposure and high oral bioavailability and achieved a viral-load
      reduction greater than 2 log in a hydrodynamic-injected (HDI) HBV mouse model and
      has now been selected for further development.

PMID- 29381359
TI  - Halogenated C15 Acetogenin Analogues of Obtusallene III from a Laurenciella sp.
      Collected in Corsica.
AB  - NMR chemical profiling of a Laurenciella sp. using a computerized method
      developed in our laboratory resulted in the identification of five new compounds
      (1-5) and 17 known compounds, among which 3-(E)-laurenyne represented by far the
      most abundant metabolite. Compounds 1 to 5 were isolated and fully characterized
      by detailed spectroscopic analysis. The absolute configuration and structural
      features of compound 1 were determined by single-crystal X-ray diffraction
      analysis. Compounds 1 to 4 are 12-membered cyclic ether acetogenins that are
      present in solution as interconverting conformers exhibiting an (aR)
      configuration of the bromoallene unit together with an S configuration at C-4.
      Among these, compound 3 is the first obtusallene derivative with bromine
      substituents at both the C-7 and C-12 positions. Compound 5 is an acetogenin
      bearing a [5.5.1]bicyclotridecane ring system. A plausible biosynthetic route to
      1-4 is proposed.

PMID- 29381360
TI  - A Coupling Approach for the Generation of alpha,alpha-Bis(enolate) Equivalents:
      Regioselective Synthesis of gem-Difunctionalized Ketones.
AB  - Regioselective alpha,alpha-difunctionalization adjacent to a ketone is a
      significant synthetic challenge. Here, we present a solution to this problem
      through the transition-metal-free coupling of esters with geminal bis(boron)
      compounds. This forms an alpha,alpha-bis(enolate) equivalent which can be trapped
      with electrophiles including alkyl halides and fluorinating agents. This presents
      an efficient, convergent synthetic strategy for the synthesis of unsymmetrical
      blocked ketones.

PMID- 29381361
TI  - Fluorine Gauche Effect Explained by Electrostatic Polarization Instead of
      Hyperconjugation: An Interacting Quantum Atoms (IQA) and Relative Energy Gradient
      (REG) Study.
AB  - We present an interacting quantum atoms (IQA) study of the gauche effect by
      comparing 1,2-difluoroethane, 1,2-dichloroethane, and three conformers of
      1,2,3,4,5,6-hexafluorocyclohexane. In the 1,2-difluoroethane, the gauche effect
      is observed in that the gauche conformation is more stable than the anti, whereas
      in 1,2-dichloroethane the opposite is true. The analysis performed here is
      exhaustive and unbiased thanks to using the recently introduced relative energy
      gradient (REG) method [ Thacker , J. C. R. ; Popelier , P. L. A. Theor. Chem. Acc
      . 2017 , 136 , 86 ], as implemented in the in-house program ANANKE. We challenge
      the common explanation that hyperconjugation is responsible for the gauche
      stability in 1,2-difluoroethane and instead present electrostatics as the cause
      of gauche stability. Our explanation of the gauche effect is also is seen in
      other molecules displaying local gauche conformations, such as the recently
      synthesized "all-cis" hexafluorocyclohexane and its conformers where all the
      fluorine atoms are in the equatorial positions. Using our extension of the
      traditional IQA methodology that allows for the partitioning of electrostatic
      terms into polarization and charge transfer, we propose that the cause of gauche
      stability is 1,3 C...F electrostatic polarization interactions. In other words,
      if a number of fluorine atoms are aligned, then the stability due to polarization
      of nearby carbon atoms is increased.

PMID- 29381362
TI  - Quantum Chemical Calculations of Monomer-Dimer Equilibria of Aromatic C-Nitroso
      Compounds.
AB  - Monomer-dimer equilibria of nitrosobenzene and 2-nitrosopyridine in gas phase and
      solution were studied by range of quantum chemical methods in an attempt to find
      the level of theory suitable for modeling dimerization reactions of aromatic C
      nitroso compounds in general. The best agreement with the experimental standard
      reaction Gibbs energies was obtained with a combination of double-hybrid density
      functionals B2PLYP-D3, PBE0DH, and DSD-PBEB86, and basis sets of triple-zeta
      quality. Of all other tested functionals, global hybrid PBE0 behaved equally
      well, and proved to be more than adequate for at least preliminary work. Other
      tested methods either produced inferior results (MP2, MP4(SDQ), CCSD, G4(MP2),
      CBS-QBS, CBS-APNO), or were too demanding for practical use (CCSD(T)). Analysis
      of computationally obtained thermodynamic data reveal intricate details of these
      reactions. Both E- and Z-dimers have several different conformers, which all have
      different solvation energies. While in the gas phase the nitrosobenzene E-dimer
      is more stable that its Z-form, in chloroform, the Z-form is more stable. Gas
      phase dimerization entropies are large and negative, so these reactions are
      strongly temperature dependent. In some cases, like with 2-nitrosopyridines,
      entropy and enthalpy terms essentially cancel each other out, allowing structural
      and media effects to significantly influence dimerization equilibria.

PMID- 29381363
TI  - Postelongation Strategy for the Introduction of Guanidinium Units in the Main
      Chain of Helical Oligourea Foldamers.
AB  - The synthesis of hybrid urea-based foldamers containing isosteric guanidinium
      linkages at selected positions in the sequence is described. We used a
      postelongation approach whereby the guanidinium moiety is introduced by direct
      transformation of a parent oligo(urea/thiourea) foldamer precursor. The method
      involves activation of the thiourea by treatment with methyl iodide and
      subsequent reaction with amines. To avoid undesired cyclization with the
      preceding urea moiety, resulting in heterocyclic guanidinium formation in the
      main chain, the urea unit preceding the thiourea unit in the sequence was
      replaced by an isoatomic and isostructural gamma-amino acid. The approach was
      extended to solid-phase techniques to accelerate the synthesis of longer and more
      functionalized sequences. Under optimized conditions, an octamer hybrid oligomer
      incorporating a central guanidinium linkage was obtained in good overall yield
      and purity. This work also reports data related to the structural consequences of
      urea by guanidinium replacements in solution and reveals that helical folding is
      substantially reduced in oligomers containing a guanidinium group.

PMID- 29381364
TI  - Frequency Control of Single Quantum Emitters in Integrated Photonic Circuits.
AB  - Generating entangled graph states of qubits requires high entanglement rates with
      efficient detection of multiple indistinguishable photons from separate qubits.
      Integrating defect-based qubits into photonic devices results in an enhanced
      photon collection efficiency, however, typically at the cost of a reduced defect
      emission energy homogeneity. Here, we demonstrate that the reduction in defect
      homogeneity in an integrated device can be partially offset by electric field
      tuning. Using photonic device-coupled implanted nitrogen vacancy (NV) centers in
      a GaP-on-diamond platform, we demonstrate large field-dependent tuning ranges and
      partial stabilization of defect emission energies. These results address some of
      the challenges of chip-scale entanglement generation.

PMID- 29381365
TI  - Biocatalytic Membrane Based on Polydopamine Coating: A Platform for Studying
      Immobilization Mechanisms.
AB  - Application of biocatalytic membrane is promising in food, pharmaceutical, and
      water treatment industries, whereas enzyme immobilization is the key step of
      biocatalytic membrane preparation. Thus, how to minimize the negative effect of
      immobilization on enzyme performance is required to answer. In this work, we
      proposed a platform for biocatalytic membrane preparation and immobilization
      mechanism investigation based on polydopamine (PDA) coating, which was
      demonstrated by immobilizing five commonly used enzymes (laccase, glucose
      oxidase, lipase, pepsin, and dextranase) on three commercially available
      membranes via three immobilization mechanisms (electrostatic attraction, covalent
      bonding, and hydrophobic adsorption), respectively. By examining the enzyme
      loading, activity, and kinetics under different immobilization mechanisms, we
      found that except for dextranase, enzyme immobilization via electrostatic
      attraction retained the most activity, whereas covalent bonding and hydrophobic
      adsorption were detrimental to enzyme conformation. Enzyme immobilization via
      covalent bonding ensured a high enzyme loading, and hydrophobic adsorption was
      only suitable for lipase and dextranase immobilization. Moreover, the properties
      of functional groups around the enzyme active center should be considered for the
      selection of suitable immobilization strategy (i.e., avoid covering the active
      center by membrane carrier). This work not only established a versatile platform
      for biocatalytic membrane preparation but also provided a novel methodology to
      evaluate the effect of immobilization mechanisms on enzyme performance.

PMID- 29381366
TI  - pH Responsive Doxorubicin Delivery by Fluorous Polymers for Cancer Treatment.
AB  - Polymeric nanoparticles have emerged as valuable drug delivery vehicles as they
      improve solubility of hydrophobic drugs, enhance circulation lifetime, and can
      improve the biodistribution profile of small-molecule therapeutics. These
      nanoparticles can take on a host of polymer architectures including polymersomes,
      hyperbranched nanoparticles, and dendrimers. We have recently reported that
      simple low molecular weight fluorous copolymers can self-assemble into
      nanoparticles and show exceptional passive targeting into multiple tumor models.
      Given the favorable biodistribution of these particles, we sought to develop
      systems that enable selective delivery in acidic environments, such as the tumor
      microenvironment or the lysosomal compartment. In this report, we describe the
      synthesis and in vitro biological studies of a pH-responsive doxorubicin (DOX)
      fluorous polymer conjugate. A propargyl DOX hydrazone was synthesized and
      covalently attached to a water-dispersible fluorous polymer composed of
      trifluoroethyl methacrylate (TFEMA) and oligo(ethylene glycol) methyl ether
      methacrylate (OEGMEMA) using the ligand-accelerated copper-catalyzed azide-alkyne
      cycloaddition. Driven by the high fluorine content of the copolymer carrier, the
      DOX-copolymer formed stable micelles under aqueous conditions with a hydrodynamic
      diameter of 250 nm. The DOX-copolymer showed internalization into multiple in
      vitro models for breast and ovarian cancer. Cytotoxicity assays demonstrated
      efficacy in both breast and ovarian cancer with overall efficacy being highly
      dependent on the cell line chosen. Taken together, these results present a
      platform for the pH-triggered delivery of DOX from a fluorous micelle carrier
      effective against multiple cancer models in vitro.

PMID- 29381367
TI  - Synergistic Effects of C/alpha-MoC and Ag for Efficient Oxygen Reduction
      Reaction.
AB  - It remains challenging to prepare highly active and stable catalysts from earth
      abundant elements for the oxygen reduction reaction (ORR). Herein we report a
      facile method to synthesize cost-effective heterogeneous C/alpha-MoC/Ag
      electrocatalysts. Rotating disc electrode (RDE) experiments revealed that the
      obtained C/alpha-MoC/Ag exhibited much superior catalytic performance for ORR
      than that of C/Ag, C/alpha-MoC, or even the conventional Pt/C. First-principles
      calculations indicated that the enhanced activity could be attributed to the
      efficient synergistic effects between Ag and alpha-MoC/C by which the energy
      barrier for O2 dissociation has been substantially reduced. Furthermore, Li-air
      and Al-air cells were assembled to demonstrate the unprecedented electrochemical
      performance of C/alpha-MoC/Ag nanocomposites surpassing the Pt/C. Thus
      experimental results and theoretical calculations together showed that the
      heterogeneous C/alpha-MoC/Ag nanocomposites are a promising alternative to
      platinum for applications in industrial metal-air batteries.

PMID- 29381368
TI  - Construction of 8-Azabicyclo[3.2.1]octanes via Sequential DDQ-Mediated Oxidative
      Mannich Reactions of N-Aryl Pyrrolidines.
AB  - A concise synthesis of 8-azabicyclo[3.2.1]octanes via sequential oxidative
      Mannich reactions is described. This approach involves an intermolecular
      oxidative Mannich coupling reaction between N-aryl pyrrolidines with TMS enol
      ether and a subsequent intramolecular oxidative Mannich cyclization of the
      corresponding silyl enol ether. DDQ is used as a key oxidant for both reactions.

PMID- 29381369
TI  - Photoinduced Multicomponent Synthesis of alpha-Silyloxy Acrylamides, an
      Unexplored Class of Silyl Enol Ethers.
AB  - The photoinduced, multicomponent reaction of alpha-diazoketones, silanols, and
      isocyanides affords alpha-silyloxy acrylamides, formally derived from alpha-keto
      amides. The presence of a secondary amido group makes classic preparative methods
      for silyl enol ethers unfeasible in this case, while the mild conditions required
      by this photochemical approach allow their synthesis in good yields; moreover,
      the general structure can be easily modified by varying each component of the
      multicomponent reaction. Fine-tuning of the reaction conditions (i.e., solvents,
      radiation, additives) can be exploited to obtain complete Z selectivity. The
      reactivity of this overlooked class of silyl enol ethers has been investigated,
      and features that could pave the way to new applications have been found.

PMID- 29381370
TI  - Synthetic Studies toward the Tetrapetalones: Diastereoselective Construction of a
      Putative Intermediate.
AB  - A strategy toward tetrapetalones was explored including a site-selective
      ethylenation of the silyl enol ether A to afford a quaternary stereocenter that
      serves in a stereogenic capacity. Regio- and diastereoselective reactions were
      observed in conjunction with the oxidative formation of cation B, which included
      subsequent selective formation of either carbon-oxygen or carbon-carbon bonds at
      the delta or zeta position on the seven-membered ring. The fourth ring was formed
      using a Stetter reaction.

PMID- 29381371
TI  - New plots in the partnerships of contemporary STEMI care: Revival of the 'menage
      a trois'?

PMID- 29381372
TI  - Thinking Differently about Risk.

PMID- 29381375
TI  - Heart rate variability biofeedback: implications for cognitive and psychiatric
      effects in older adults.
AB  - OBJECTIVES: Two decades of heart rate variability (HRV) biofeedback research have
      focused on adolescent and adult populations with a variety of symptoms and
      conditions at the exclusion of older adults. This study explores HRV biofeedback
      as a novel treatment to decrease psychiatric symptoms and improve cognitive
      functioning in older adults. METHODS: Participants enrolled in a three-week
      intervention that included six 30-min biofeedback sessions. Neuropsychological
      and psychiatric measures were administered before and after the intervention.
      RESULTS: Decreases in depression (Cohen's d = 1.02, p < .001), state anxiety
      (Cohen's d = 0.82, p = .003), and trait anxiety (Cohen's d = 0.84, p = .002) were
      observed. An increase in attentional skills as measured by the Trail Making Test 
      Part A was seen (Cohen's d = 1.00, p = .001). Differences in executive skills as
      measured by the Trial Making Test - Part B and the Stroop Task did not reach
      statistical significance. CONCLUSION: This study suggests that older adults may
      benefit from HRV biofeedback interventions much like the younger populations that
      have been studied for decades. Depression, anxiety, and attentional skills were
      positively affected. Several participants reported improved sleep quality and
      stress management. Future studies should corroborate these findings.

PMID- 29381374
TI  - Humans with obesity have disordered brain responses to food images during
      physiological hyperglycemia.
AB  - Blood glucose levels influence brain regulation of food intake. This study
      assessed the effect of mild physiological hyperglycemia on brain response to food
      cues in individuals with obesity (OB) versus normal weight individuals (NW).
      Brain responses in 10 OB and 10 NW nondiabetic healthy adults [body mass index:
      34 (3) vs. 23 (2) kg/m2, means (SD), P < 0.0001] were measured with functional
      MRI (blood oxygen level-dependent contrast) in combination with a two-step
      normoglycemic-hyperglycemic clamp. Participants were shown food and nonfood
      images during normoglycemia (~95 mg/dl) and hyperglycemia (~130 mg/dl). Plasma
      glucose levels were comparable in both groups during the two-step clamp ( P = not
      significant). Insulin and leptin levels were higher in the OB group compared with
      NW, whereas ghrelin levels were lower (all P < 0.05). During hyperglycemia,
      insula activity showed a group-by-glucose level effect. When compared with
      normoglycemia, hyperglycemia resulted in decreased activity in the hypothalamus
      and putamen in response to food images ( P < 0.001) in the NW group, whereas the
      OB group exhibited increased activity in insula, putamen, and anterior and
      dorsolateral prefrontal cortex (aPFC/dlPFC; P < 0.001). These data suggest that
      OB, compared with NW, appears to have disruption of brain responses to food cues
      during hyperglycemia, with reduced insula response in NW but increased insula
      response in OB, an area involved in food perception and interoception. In a post
      hoc analysis, brain activity in obesity appears to be associated with
      dysregulated motivation (striatum) and inappropriate self-control (aPFC/dlPFC) to
      food cues during hyperglycemia. Hyperstimulation for food and insensitivity to
      internal homeostatic signals may favor food consumption to possibly play a role
      in the pathogenesis of obesity.

PMID- 29381376
TI  - Proanthocyanidins in cereals and pseudocereals.
AB  - Proanthocyanidins (PAs) are a class of oligomeric flavonoids found in a variety
      of plant foods. Intake of PAs in human diet has been associated with a reduced
      occurrence of various chronic disorders. Cereal and pseudocereal grains are
      staple food items. Grain genotypes containing PAs can be developed as functional
      foods to efficiently improve human health. This review summarises the occurrence
      of PAs in diverse grains, including rice, wheat, barley, sorghum, millets,
      buckwheat, and some forage grasses. Great diversity in PA structure and
      composition has been recorded. The biological activities of the grain PAs, such
      as antioxidant, antiinflammatory, anticancer, and antidiabetic capacities, are
      also reviewed. The bioavailability and metabolism of grain PAs in human digestive
      tract are discussed. Future research directions are suggested on how to improve
      our understandings of the chemistry of PAs in cereals and pseudocereals and of
      the biological properties for human health applications.

PMID- 29381378
TI  - Incidentally Detected Bilateral Adrenal Nodules in Patients Without Cancer: Is
      Further Workup Necessary?
AB  - OBJECTIVE: The purpose of this study was to determine the rate of malignancy in
      incidentally detected bilateral adrenal masses in patients with no known history
      of cancer. MATERIALS AND METHODS: A retrospective search of CT reports of
      patients with incidentally detected bilateral adrenal nodules was performed from
      January 1, 2002, to January 1, 2014. Patients were excluded if they had a known
      cancer or suspected functioning adrenal tumor; 161 patients were included.
      Nodules were characterized as benign or malignant on the basis of imaging
      features at the index CT examination, imaging features at subsequent adrenal
      protocol CT or MRI, imaging stability for a minimum of 1 year, or clinical follow
      up of a minimum of 2 years. RESULTS: Mean nodule size was 1.8 cm (range, 0.7-4.9
      cm). There were no cases of primary or secondary adrenal malignancy (95% CI, 0.00
      0.023). The nodules diagnosed on index CT scans were 73 adrenal adenomas and two
      myelolipomas. Seventy-four nodules were subsequently characterized as adrenal
      adenomas on the basis of imaging findings. Of the 113 indeterminate nodules that
      had imaging follow-up, 111 were stable at the latest follow-up examination. One
      nodule grew 26% over 8.1 years, and the other grew 59% over 12.4 years. Clinical
      follow-up of patients with 60 indeterminate nodules revealed no evidence of
      adrenal malignancy. CONCLUSION: No case of malignancy was found in 322
      incidentally detected bilateral adrenal nodules at CT of patients without known
      cancer. Imaging follow-up of such lesions may be unnecessary.

PMID- 29381377
TI  - Radiologic Correlation Between the Ischiofemoral Space and Morphologic
      Characteristics of the Hip in Hips With Symptoms of Dysplasia.
AB  - OBJECTIVE: The purpose of this study was to investigate radiologic correlation
      between the ischiofemoral space and morphologic findings in the hip in patients
      with symptomatic developmental dysplasia of the hip (DDH), borderline DDH, and
      femoroacetabular impingement (FAI). MATERIALS AND METHODS: In 84 patients
      undergoing hip arthroscopic surgery, 108 hips were divided into three groups
      according to lateral center-edge angle (LCEA): DDH group (LCEA < 20 degrees ; 18
      hips), borderline DDH group (20 degrees  <= LCEA < 25 degrees ; 26 hips), and FAI
      group (LCEA >= 25 degrees ; 64 hips). Ischiofemoral distance was evaluated by
      radiography and ischiofemoral space and quadratus femoris space by MRI. Software
      was used to measure the radiographic parameters LCEA, femoral neck-shaft angle,
      and femoral neck anteversion on preoperative CT scans. RESULTS: Ischiofemoral
      distance, ischiofemoral space, and quadratus femoris space were significantly
      smaller in the DDH and borderline DDH groups than in the FAI group. The
      prevalence of hips with ischiofemoral space < 17 mm was significantly higher in
      the DDH (10 of 18 patients [56%]) and borderline DDH (8 of 26 patients [31%])
      groups than in the FAI group (4 of 64 patients [6%]). In addition, the prevalence
      of hips with a quadratus femoris space < 8 mm was significantly higher in the DDH
      (2 of 18 patients [11%]) and borderline DDH (3 of 26 patients [12%]) groups than
      in the FAI (0 of 64 patients [0%]) group. Femoral neck-shaft angle and femoral
      neck anteversion were significantly greater in the DDH group than in the FAI
      group. CONCLUSION: Ischiofemoral impingement syndromes can be considered more
      likely in patients with DDH than in those with FAI.

PMID- 29381379
TI  - Comparing Dose-Length Product-Based and Monte Carlo Simulation Organ-Based
      Calculations of Effective Dose in 16- and 64-MDCT Examinations Using Automatic
      Tube Current Modulation.
AB  - OBJECTIVE: The purpose of this study is to compare dose-length product (DLP)
      based calculation of effective dose (EDDLP) with Monte Carlo simulation organ
      based calculation of effective dose (EDMCO) in 16- and 64-MDCT examinations, with
      the use of clinical examinations with automatic tube current modulation.
      MATERIALS AND METHODS: Dose data were obtained from 50 consecutive unenhanced
      head CT examinations, unenhanced chest CT examinations, and unenhanced and
      contrast-enhanced abdominopelvic CT examinations performed using 16- and 64-MDCT
      scanners, as well as from 50 pulmonary CT angiography (CTA) examinations
      performed using a 64-MDCT scanner and 31 pulmonary CTA examinations performed
      using a 16-MDCT scanner. The EDMCO and the mean patient effective diameter were
      calculated using commercially available software. The EDDLP was also calculated.
      Both the mean difference and percentage difference between EDDLP and EDMCO were
      calculated, and they were statistically compared according to patient sex, type
      of examination performed, and type of scanner used. RESULTS: EDDLP significantly
      underestimated the EDMCO by 0.3 mSv (19%) for men who underwent unenhanced head
      CT, 0.5 mSv (29%) for women who underwent unenhanced head CT, 0.9-1.4 mSv (9-13%)
      for men who underwent chest CT, and 4.7-4.8 mSv (39%) for women who underwent
      chest CT (p < 0.001). The EDDLP overestimated the EDMCO by 1.9-2.0 mSv (12-14%)
      for men who underwent abdominopelvic CT (p < 0.001), with no significant
      difference noted for women who underwent abdominopelvic CT's. No significant
      difference was noted in the percentage difference in ED between the 16- and 64
      MDCT scanners (p >= 0.13). CONCLUSION: EDDLP underestimates EDMCO, the reference
      standard for dose calculation, by 19-39% in unenhanced head CT examinations and,
      among women, in chest CT examinations. EDDLP deviates from EDMCO by less than 15%
      for chest CT examinations of men and for abdominopelvic CT. These differences can
      be attributed to variable patient body habitus, automatic tube current
      modulation, and sex-neutral k-coefficients, and they should be considered when
      calculating ED, particularly in women.

PMID- 29381380
TI  - The Diagnostic Performance of MRI for Detection of Lymph Node Metastasis in
      Bladder and Prostate Cancer: An Updated Systematic Review and Diagnostic Meta
      Analysis.
AB  - OBJECTIVE: The purpose of this article is to review the diagnostic performance of
      MRI for the detection of pelvic lymph node (LN) metastasis in patients with
      bladder and prostate cancer. MATERIALS AND METHODS: MEDLINE and EMBASE were
      searched up to January 13, 2017. We included diagnostic accuracy studies that
      used MRI for pelvic LN detection in patients with bladder or prostate cancer,
      using histopathologic analyses published since 2000 as the reference standard.
      Two independent reviewers assessed the methodologic quality using the Quality
      Assessment of Diagnostic Accuracy Studies-2 tool. Sensitivity and specificity of
      all studies were calculated. Per-patient and per-LN results were pooled and
      plotted in a hierarchic summary ROC plot. Metaregression, sensitivity, and
      subgroup analyses were performed. RESULTS: Twenty-four studies (2928 patients)
      were included. Pooled per-patient sensitivity (n = 21) was 0.56 (95% CI, 0.42
      0.69) with a specificity of 0.94 (95% CI, 0.90-0.96). Per-LN pooled estimates (n
      = 9) showed consistent results: sensitivity of 0.57 (95% CI, 0.29-0.82) and
      specificity of 0.97 (95% CI, 0.94-0.98). At metaregression analysis, type of
      cancer, magnet field strength, and use of ultrasmall superparamagnetic particles
      of iron oxide (USPIO) were significant factors affecting heterogeneity (p <=
      0.01). Sensitivity analyses showed that specificity estimates were comparable
      (range, 0.87-0.95), but sensitivity estimates showed significant differences.
      Studies that used USPIO (n = 4) had higher sensitivity (0.86; 95% CI, 0.62-0.96)
      than did those not using USPIO (n = 17; 0.46; 95% CI, 0.35-0.58). CONCLUSION: MRI
      shows high specificity but poor and heterogeneous sensitivity for detecting
      pelvic LN metastasis in patients with bladder and prostate cancer. Using USPIO
      can improve sensitivity.

PMID- 29381381
TI  - Axillary Ultrasound Identifies Residual Nodal Disease After Chemotherapy: Results
      From the American College of Surgeons Oncology Group Z1071 Trial (Alliance).
AB  - OBJECTIVE: The purpose of this study is to determine lymph node features on
      axillary ultrasound (US) images obtained after neoadjuvant chemotherapy that are
      associated with residual nodal disease in patients with initial biopsy-proven
      node-positive breast cancer. SUBJECTS AND METHODS: All patients had axillary US
      performed after neoadjuvant chemotherapy. Axillary US images were centrally
      reviewed for lymph node size, cortical thickness, and cortical morphologic
      findings (type I indicated no visible cortex; type II, a hypoechoic cortex <= 3
      mm; type III, a hypoechoic cortex > 3 mm; type IV, a generalized lobulated
      hypoechoic cortex; type V, focal hypoechoic cortical lobulation; and type VI, a
      totally hypoechoic node with no hilum). Lymph node characteristics were compared
      with final surgical pathologic findings. RESULTS: Axillary US images obtained
      after neoadjuvant chemotherapy and surgical pathologic findings were available
      for 611 patients. Residual nodal disease was present in 373 patients (61.0%), and
      238 (39.0%) had a complete nodal pathologic response. Increased cortical
      thickness (mean, 3.5 mm for node-positive disease vs 2.5 mm for node-negative
      disease) was associated with residual nodal disease. Lymph node short-axis and
      long-axis diameters were significantly associated with pathologic findings.
      Patients with nodal morphologic type I or II had the lowest rate of residual
      nodal disease (51 of 91 patients [56.0%] and 138 of 246 patients (56.1%),
      respectively), whereas those with nodal morphologic type VI had the highest rate
      (44 of 55 patients [80.0%]) (p = 0.004). The presence of fatty hilum was
      significantly associated with node-negative disease (p = 0.0013). CONCLUSION:
      Axillary US performed after neoadjuvant chemotherapy is useful for nodal response
      assessment, with longer short-axis diameter, longer long-axis diameter, increased
      cortical thickness, and absence of fatty hilum significantly associated with
      residual nodal disease after neoadjuvant chemotherapy.

PMID- 29381382
TI  - Grading System to Categorize Breast MRI in BI-RADS 5th Edition: A Multivariate
      Study of Breast Mass Descriptors in Terms of Probability of Malignancy.
AB  - OBJECTIVE: The purpose of this study is to analyze the association between the
      probability of malignancy and breast mass descriptors in the BI-RADS 5th edition
      and to devise criteria for grading mass lesions, including subcategorization of
      category 4 lesions with or without apparent diffusion coefficient (ADC) values.
      MATERIALS AND METHODS: A total of 519 breast masses in 499 patients were
      selected. Breast MRI was performed with a 1.5-T MRI scanner using a 16-channel
      dedicated breast radiofrequency coil. Two radiologists determined the morphologic
      and kinetic features of the breast masses. Mean ADC values were measured on ADC
      maps by placing round ROIs that encircled the largest possible solid mass
      portions. An optimal ADC threshold was chosen to maximize the Youden index.
      Corresponding pathologic diagnoses were obtained by either biopsy or surgery.
      RESULTS: A total of 472 masses were malignant. Multivariate model analysis showed
      that shape (irregular, p < 0.001), margin type (not circumscribed, p < 0.001),
      internal enhancement (rim enhancement and heterogeneous enhancement, p = 0.0001),
      and delayed phase (washout, p = 0.0003) were the significant explanatory
      variables. The 3-point scoring system for findings suspicious for malignancy and
      the proposed classification system for breast mass descriptors (with points for
      category designation ranging from 0 to > 4) were significant with respect to
      malignancy (p < 0.01). The inclusion of ADC values improved the positive
      predictive values for categories 3, 4A, and 4B. CONCLUSION: The 3-point scoring
      system for findings suspicious for malignancy and the proposed classification
      system for breast mass descriptors would be valid as a categorization system. ADC
      values may be used to downgrade benign lesions in categories 3, 4A, and 4B.

PMID- 29381383
TI  - Atrial fibrillation and its complications in arterial hypertension: The potential
      preventive role of omega-3 polyunsaturated fatty acids.
AB  - Atrial fibrillation (AF) is the most common type of arrhythmia in the general
      population with a prevalence that reaches one third of patients with arterial
      hypertension. Several risk factors frequently associated with hypertension
      predispose the myocardium to AF by inducing atrial inflammation and fibrosis and
      altering atrial electrical and mechanical characteristics. AF influences the
      quality of life of hypertensive patients since it increases incidence of stroke
      and other thromboembolic events, and mortality. Polyunsaturated fatty acids of
      the omega-3 family (omega-3 PUFA) have been demonstrated to be beneficial in
      cardiovascular disease prevention by reducing plasma lipids and blood pressure
      levels and decreasing the risk of sudden death. These fatty acids can act as
      potent anti-inflammatory and anti-arrhythmic agents. Many studies have
      investigated a possible preventive effect of omega-3 PUFA on incident AF
      reporting contradictory results. This article overviews the evidence currently
      available on this important topic and provides some conclusive remarks on the
      possibility that these fatty acids could be beneficial in hypertensive patients.

PMID- 29381384
TI  - Astringency, bitterness and color changes in dry red wines before and during oak
      barrel aging: An updated phenolic perspective review.
AB  - To understand effects of using oak barrels on the astringency, bitterness and
      color of dry red wines, phenolic reactions in wines before and after barrel aging
      are reviewed in this paper, which has been divided into three sections. The first
      section includes an introduction to chemical reactivities of grape-derived
      phenolic compounds, a summary of the phenolic reactions that occur in dry red
      wines before barrel aging, and a discussion of the effects of these reactions on
      wine astringency, bitterness and color. The second section introduces barrel
      types that determine the oak barrel constituents in wines (primarily oak
      aldehydes and ellagitannins) and presents reactions between the oak constituents
      and grape-derived phenolic compounds that may modulate wine astringency,
      bitterness and color. The final section illustrates the chemical differences
      between basic oxidation and over-oxidation in wines, discusses oxygen consumption
      kinetics in wines during barrel aging by comparing different oxygen consumption
      kinetics observed previously by others, and speculates on the possible
      preliminary phenolic reactions that occur in dry red wines during oak barrel
      aging that soften tannins and stabilize pigments via basic oxidation.
      Additionally, sulfur dioxide (SO2) addition during barrel aging and suitability
      of adopting oak barrels for aging wines are briefly discussed.

PMID- 29381385
TI  - Influence of functional food components on gut health.
AB  - Intestinal epithelial cells (IECs) lining the gastrointestinal tract establish a
      barrier between external environments and the internal milieu. An intact
      intestinal barrier maintains gut health and overall good health of the body by
      preventing from tissue injury, pathogen infection and disease development. When
      the intestinal barrier function is compromised, bacterial translocation can
      occur. Our gut microbiota also plays a fundamentally important role in health,
      for example, by maintaining intestinal barrier integrity, metabolism and
      modulating the immune system, etc. Any disruption of gut microbiota composition
      (also termed dysbiosis) can lead to various pathological conditions. In short,
      intestinal barrier and gut microbiota are two crucial factors affecting gut
      health. The gastrointestinal tract is a complex environment exposed to many
      dietary components and commensal bacteria. Dietary components are increasingly
      recognized to play various beneficial roles beyond basic nutrition, resulting in
      the development of the functional food concepts. Various dietary modifiers,
      including the consumption of live bacteria (probiotics) and ingestible food
      constituents such as prebiotics, as well as polyphenols or synbiotics
      (combinations of probiotics and prebiotics) are the most well characterized
      dietary bioactive compounds and have been demonstrated to beneficially impact the
      gut health and the overall well-being of the host. In this review we depict the
      roles of intestinal epithelium and gut microbiota in mucosal defence responses
      and the influence of certain functional food components on the modulation of gut
      health, with a particular focus on probiotics, prebiotics and polyphenols.

PMID- 29381386
TI  - Prevention and treatment effects of edible berries for three deadly diseases:
      Cardiovascular disease, cancer and diabetes.
AB  - Cardiovascular disease (CVD), cancer and diabetes are serious threat to human
      health and more and more aroused people's attention. It is important to find the
      safe and effective prevention and treatment methods for the three deadly
      diseases. At present, a generally attention in the possible positive effects of
      edible berries for the three deadly diseases has been noted. Berry phytochemical
      compounds regulate different signaling pathways about cell survival, growth and
      differentiation. They contribute to the prevention and treatment of CVD, cancer
      and diabetes. This article reviews previous experimental evidence, several common
      berry phytochemical compounds and their possible mechanisms involved in three
      deadly diseases were summarized.

PMID- 29381387
TI  - Cognitive functioning among cognitively intact dementia caregivers compared to
      matched self-selected and population controls.
AB  - PURPOSE OF THE STUDY: Caregiving for a person with dementia is frequently used to
      model the impact of chronic stress on health, including cognitive functioning.
      However, the prevalence of typically healthier, self-selecting non-caregiving
      control groups could contribute to a picture of poorer caregiver performance and
      overstate the negative effects of stress. We investigated differences in
      cognitive performance between dementia caregivers and two groups of non
      caregivers recruited using different sampling methods. DESIGN AND METHODS: We
      compared cognitive function and psychological wellbeing among 252 spousal
      dementia caregivers with demographically matched non-caregiving control groups
      drawn from (1) a population study and (2) a self-selecting sample. Comparable
      cognitive measures included immediate and delayed recall, processing speed
      reaction time and verbal fluency. RESULTS: Caregiver and non-caregiver
      performance was comparable on most cognitive domains. However, caregivers
      outperformed both control groups on processing speed (p <= .05) and reaction time
      (p <= .05), despite having higher levels of stress and depression (ps < .001).
      Furthermore, caregivers had significantly better free recall than self-selecting
      controls (p < .001). IMPLICATIONS: Our results, overall, do not support the idea
      that caregiving is associated with stress-induced cognitive deficits. Rather, the
      trend toward better caregiver performance is consistent with the healthy
      caregiver hypothesis.

PMID- 29381388
TI  - Long-Acting Injectable Atypical Antipsychotic Use in Adolescents: An
      Observational Study.
AB  - OBJECTIVES: Although second generation long-acting injectable antipsychotics (SG
      LAIAs) have been approved and are widely used in adults, there is limited
      evidence for the use of long-acting formulations in children and adolescents.
      Thus, we systematically describe the off-label use of SG-LAIAs in clinical
      practice in adolescent inpatients. METHODS: All individuals admitted to our
      Children and Adolescent Inpatient Psychiatry Unit receiving treatment with SG
      LAIAs between January 2013 and June 2016 were reviewed. A retrospective analysis
      of medical records was conducted. Clinical diagnoses were established using DSM-5
      criteria. RESULTS: Thirty individuals (53.3% female) out of a total of 1,148
      admitted patients (2.6%) were identified. The mean age was 16.3 (SD = 1.3; range:
      12.5-17.9).The main diagnoses were psychosis (70%) and disruptive behavior
      disorders (DBDs) (30%), although comorbidity was frequent (96.6%), especially
      drug use (55.2%, mostly cannabis). SG-LAIAs used were aripiprazole (40%),
      risperidone (36.7%), and paliperidone palmitate (23.3%), and the main reasons
      were a history of low compliance (90%) and/or poor insight (73.3%). A mean
      improvement of 31.7 (SD = 8.7) between admission and discharge was registered in
      the Children's Global Assessment Scale (CGAS); no differences were observed
      between different SG-LAIAs. Although they were generally well tolerated, 23.3% of
      patients reported mild short-term side effects, which were more frequent with
      risperidone than with aripiprazole (p = .014). CONCLUSIONS: Our clinical
      experience suggests that SG-LAIAs may be a safe treatment option during
      adolescence in inpatients with psychotic disorders, as well as with DBD. No
      differences were found in CGAS improvement scores between the three SGA-LAIAs
      used, although patients on risperidone reported more side effects than those on
      aripiprazole. Further research is needed so as to evaluate safety and
      effectiveness of SG-LAIAs in this population.

PMID- 29381389
TI  - A critical review on the use of artificial neural networks in olive oil
      production, characterization and authentication.
AB  - Artificial neural networks (ANN) are computationally based mathematical tools
      inspired by the fundamental cell of the nervous system, the neuron. ANN
      constitute a simplified artificial replica of the human brain consisting of
      parallel processing neural elements similar to neurons in living beings. ANN is
      able to store large amounts of experimental information to be used for
      generalization with the aid of an appropriate prediction model. ANN has proved
      useful for a variety of biological, medical, economic and meteorological
      purposes, and in agro-food science and technology. The olive oil industry has a
      substantial weight in Mediterranean's economy. The different steps of the olive
      oil production process, which include olive tree and fruit care, fruit harvest,
      mechanical and chemical processing, and oil packaging have been examined in depth
      with a view to their optimization, and so have the authenticity, sensory
      properties and other quality-related properties of olive oil. This paper reviews
      existing literature on the use of bioinformatics predictive methods based on ANN
      in connection with the production, processing and characterization of olive oil.
      It examines the state of the art in bioinformatics tools for optimizing or
      predicting its quality with a view to identifying potential deficiencies or
      aspects for improvement.

PMID- 29381391
TI  - Do religious activities among young-old immigrants act as a buffer against the
      effect of a lack of resources on well-being?
AB  - OBJECTIVES: Despite a large body of sociological and psychological literature
      suggesting that religious activities may mitigate the effects of stress, few
      studies have investigated the beneficial effects of religious activities among
      immigrants. Immigrants in particular may stand to benefit from these activities
      because they often report a religious affiliation and often occupy disadvantaged
      positions. This study investigates whether private and public religious
      activities reduce the negative effects of a lack of physical, social, and socio
      economic resources on wellbeing among Turkish and Moroccan young-old immigrants
      in the Netherlands. METHOD: Using data from the Longitudinal Study Amsterdam,
      cluster analysis revealed three patterns of absence of resources: physically
      disadvantaged, multiple disadvantages, and relatively advantaged. Linear
      regression analysis assessed associations between patterns of resources,
      religious activities and wellbeing. RESULTS: Persons who are physically
      disadvantaged or have multiple disadvantages have a lower level of wellbeing
      compared to persons who are relatively advantaged.  More engagement in private
      religious activities was associated with higher wellbeing. Among those with
      multiple disadvantages, however, more engagement in private religious activities
      was associated with lower wellbeing. Public religious activities were not
      associated with wellbeing in the disadvantaged group. CONCLUSION: Private
      religious activities are positively related to wellbeing among Turkish and
      Moroccan immigrants. In situations where resources are lacking, however, the
      relation between private religious activities and wellbeing is negative. The
      study's results highlight the importance of context, disadvantage and type of
      religious activity for wellbeing.

PMID- 29381392
TI  - Prognostic factors in childhood-acquired brain injury.
AB  - BACKGROUND: A long-term follow-up study comparing children after anoxic brain
      injury (AnBI) with those after traumatic brain injury (TBI) was conducted, and
      prognostic factors were mapped. METHODS: A prospective historical study following
      long-term functional outcome after childhood brain injury was conducted in two
      phases. The first phase included patients suffering from moderate-severe TBI. The
      second phase assessed children after AnBI, and the results were compared.
      Functional outcome was recorded and factors influencing prognosis were outlined.
      RESULTS: On admission vegetative state (VS) was twice as prevalent in the AnBI
      subgroup. Approximately 90% of children with TBI and 60% of patients with AnBI
      gained independency in activities of daily living (ADL) and mobility. Long-term
      positive outcome, i.e., return to school and open-market employment, were higher
      in patients with TBI when compared with AnBI (61% and 48.1%, respectively).
      Significant outcome-predicting factors were VS at admission to rehabilitation,
      length of loss of consciousness (LOC) up to 11 days and functional independence
      measure (FIM) score at admission and discharge. Aetiology was not found to be a
      predicting factor. CONCLUSIONS: Duration of unconsciousness is the main long-term
      negative prognostic outcome factor. Anoxic brain damage, associated with longer
      periods of unconsciousness also heralds a less favourable outcome.

PMID- 29381390
TI  - Associations between subclinical depressive symptoms and reduced brain volume in
      middle-aged to older adults.
AB  - OBJECTIVES: The associations between subclinical depressive symptoms, as well
      specific symptom subscales, on brain structure in aging are not completely
      elucidated. This study investigated the extent to which depressive symptoms were
      related to brain volumes in fronto-limbic structures in a sample of middle-aged
      to older adults. METHOD: Eighty participants underwent structural neuroimaging
      and completed the Beck Depression Inventory, 2nd Edition (BDI-II), which
      comprises separate affective, cognitive, and somatic subscales. Gray matter
      volumes were extracted from the caudal and rostral anterior cingulate, posterior
      cingulate, hippocampus, and amygdala. Hierarchical regression models examined the
      relationship between brain volumes and (i) total depressive symptoms and (ii) BDI
      II subscales were conducted. RESULTS: After adjusting for total intracranial
      volume, race, and age, higher total depressive symptoms were associated with
      smaller hippocampal volume (p = 0.005). For the symptom subscales, after
      controlling for the abovementioned covariates and the influence of the other
      symptom subscales, more somatic symptoms were related to smaller posterior
      cingulate (p = 0.025) and hippocampal (p < 0.001) volumes. In contrast, the
      affective and cognitive subscales were not associated with brain volumes in any
      regions of interest. CONCLUSION: Our data showed that greater symptomatology was
      associated with smaller volume in limbic brain regions. These findings provide
      evidence for preclinical biological markers of major depression and specifically
      advance knowledge of the relationship between subclinical depressive symptoms and
      brain volume. Importantly, we observed variations by specific depressive symptom
      subscales, suggesting a symptom-differential relationship between subclinical
      depression and brain volume alterations in middle-aged and older individuals.

PMID- 29381393
TI  - SATB1 is a Novel Molecular Target for Cancer Therapy.
AB  - The special AT-rich sequence binding-protein1 (SATB1) attracts excessive
      attention due to its high expression in a variety of malignancies. SATB1
      reprograms chromatin and transcription profiles to promote tumor cell growth and
      invasion and inhibit apoptosis, leading to tumor progression and metastasis.
      Consistently, silencing SATB1 with small interfering RNA inhibits the growth and
      invasion of some kinds of tumors. In this review, we highlight recent progress in
      our understanding of the role of SATB1 as global regulator of gene expression
      during cancer development, and evaluate the potential of SATB1 as a molecular
      therapeutic target for cancers with aberrant SATB1 expression.

PMID- 29381394
TI  - Validation of a booted finite element model of the WIAMan ATD lower limb in
      component and whole-body vertical loading impacts with an assessment of the boot
      influence model on response.
AB  - OBJECTIVE: A novel anthropomorphic test device (ATD) representative of the 50th
      percentile male soldier is being developed to predict injuries to a vehicle
      occupant during an underbody blast (UBB). The main objective of this study was to
      develop and validate a finite element (FE) model of the ATD lower limb outfitted
      with a military combat boot and to insert the validated lower limb into a model
      of the full ATD and simulate vertical loading experiments. METHODS: A Belleville
      desert combat boot model was assigned contacts and material properties based on
      previous experiments. The boot model was fit to a previously developed model of
      the barefoot ATD. Validation was performed through 6 matched pair component tests
      conducted on the Vertically Accelerated Loads Transfer System (VALTS). The load
      transfer capabilities of the FE model were assessed along with the force
      mitigating properties of the boot. The booted lower limb subassembly was then
      incorporated into a whole-body model of the ATD. Two whole-body VALTS experiments
      were simulated to evaluate lower limb performance in the whole body. RESULTS: The
      lower limb model accurately predicted axial loads measured at heel, tibia, and
      knee load cells during matched pair component tests. Forces in booted simulations
      were compared to unbooted simulations and an amount of mitigation similar to that
      of experiments was observed. In a whole-body loading environment, the model
      kinematics match those recorded in experiments. The shape and magnitude of
      experimental force-time curves were accurately predicted by the model.
      Correlation between the experiments and simulations was backed up by high
      objective rating scores for all experiments. CONCLUSION: The booted lower limb
      model is accurate in its ability to articulate and transfer loads similar to the
      physical dummy in simulated underbody loading experiments. The performance of the
      model leads to the recommendation to use it appropriately as an alternative to
      costly ATD experiments.

PMID- 29381395
TI  - Differential expression of miRNAs are associated with the insulin signaling
      pathway in preeclampsia and gestational hypertension.
AB  - OBJECTIVES: The objective of this study was to determine microRNAs (miRNAs)
      expression levels in placental tissue and serum samples from preeclampsia (PE)
      and gestational hypertensive (GH) patients. STUDY DESIGN: Using a targeted qPCR
      method, the selected miRNAs putatively involved in the PE and GH were examined
      from normotensive (n = 32), PE (n = 32) and GH (n = 28) in South African women.
      Western blot analysis of protein expressions of AKT and PI3K was performed in the
      placental tissue of all three groups. RESULTS: qPCR results of serum miR-222
      expression levels showed a significant decrease in PE compared to GH and
      normotensive groups. miR-29a expression levels were significantly increased in PE
      and GH groups compared to normotensives. Serum expression levels of miR-181a in
      GH showed a significant increase compared to the PE and normotensive groups.
      Placental tissue expression levels of miR-181a were significantly increased in PE
      and GH groups compared to normotensives. Western blot results of placental tissue
      showed a decrease in the expression levels of AKT-serine and threonine in the PE
      groups compared to the normotensives and a significantly higher expression in the
      GH groups compared to normotensives. Phosphatidyl-inositol-3 kinase (PI3K)
      expression levels were significantly decreased in PE and GH groups compared to
      normotensives. CONCLUSION: The present study, interestingly, demonstrates the
      differential expression of circulating miRNA in GH and a correlation between the
      expression levels of miRNAs with AKT/PI3K in the insulin signaling pathway,
      reinforcing the presence of metabolic dysregulation in PE and GH.

PMID- 29381396
TI  - Diffuse axonal injury after traumatic brain injury is a prognostic factor for
      functional outcome: a systematic review and meta-analysis.
AB  - OBJECTIVE: To determine the prognosis of adult patients with traumatic brain
      injury (TBI) and diffuse axonal injury (DAI). METHODS: Online search (PubMed,
      Embase and Ovid Science Direct) of articles providing information about outcome
      in (1) patients with DAI in general, (2) DAI vs. non-DAI, (3) related to magnetic
      resonance imaging (MRI) classification and (4) related to lesion location/load. A
      reference check and quality assessment were performed. RESULTS: A total of 32
      articles were included. TBI patients with DAI had a favourable outcome in 62%.
      The risk of unfavourable outcome in TBI with DAI was three times higher than in
      TBI without DAI. Odds ratio (OR) for unfavourable outcome was 2.9 per increase of
      DAI grade on MRI. Lesions located in the corpus callosum were associated with an
      unfavourable outcome. Other specific lesion locations and lesions count showed
      inconsistent results regarding outcome. Lesion volume was predictive for outcome
      only on apparent diffusion coefficient and fluid attenuation inversion recovery
      MRI sequences. CONCLUSIONS: Presence of DAI on MRI in patients with TBI results
      in a higher chance of unfavourable outcome. With MRI grading, OR for unfavourable
      outcome increases threefold with every grade. Lesions in the corpus callosum in
      particular are associated with an unfavourable outcome.

PMID- 29381397
TI  - Surveillance of traffic incident management-related occupational fatalities in
      Kentucky, 2005-2016.
AB  - OBJECTIVE: Traffic incidents occurring on roadways require the coordinated effort
      of multiple responder and recovery entities, including communications, law
      enforcement, fire and rescue, emergency medical services, hazardous materials,
      transportation agencies, and towing and recovery. The objectives of this study
      were to (1) identify and characterize transportation incident management (TIM)
      related occupational fatalities; (2) assess concordance of surveillance data
      sources in identifying TIM occupations, driver vs. pedestrian status, and
      occupational fatality incident location; and (3) determine and compare U.S.
      occupational fatality rates for TIM industries. METHODS: The Kentucky Fatality
      Assessment and Control Evaluation (FACE) program analyzed 2005-2016 TIM
      occupational fatality data using multiple data sources: death certificate data,
      Collision Report Analysis for Safer Highways (CRASH) data, and media reports,
      among others. Literal text analysis was performed on FACE data, and a multiple
      linear regression model and SAS proc sgpanel were used to estimate and visualize
      the U.S. TIM occupational mortality trend lines and confidence bounds. RESULTS:
      There were 29 TIM fatalities from 2005 to 2015 in Kentucky; 41% of decedents were
      in the police protection occupation, and 21% each were in the fire protection and
      motor vehicle towing industries. Over one half of the TIM decedents were
      performing work activities as pedestrians when they died. Media reports
      identified the majority of the occupational fatalities as TIM related (28 of 29
      TIM-related deaths); the use of death certificates as the sole surveillance data
      source only identified 17 of the 29 deaths as TIM related, and the use of CRASH
      data only identified 4 of the 29 deaths as TIM related. Injury scenario text
      analysis showed that law enforcement vehicle pursuit, towing and recovery vehicle
      loading, and disabled vehicle response were particular high-risk activities that
      led to TIM deaths. Using U.S. data, the motor vehicle towing industry had a
      significantly higher risk for occupational mortality compared to the fire
      protection and police protection industries. CONCLUSIONS: Multiple data sources
      are needed to comprehensively identify TIM fatalities and to examine the
      circumstances surrounding TIM fatalities, because no one data source in itself
      was adequate and undercounted the total number of TIM fatalities. The motor
      vehicle towing industry, in particular, is at elevated risk for occupational
      mortality, and targeted mandatory TIM training for the motor vehicle towing
      industry should be considered. In addition, enhanced law enforcement roadside
      safety training during vehicle pursuit and apprehension of suspects is
      recommended.

PMID- 29381398
TI  - The Activity of Class I-IV Alcohol Dehydrogenase Isoenzymes and Aldehyde
      Dehydrogenase in Bladder Cancer Cells.
AB  - OBJECTIVES: The aim of this study was to determine the differences in the
      activity of Alcohol Dehydrogenase (ADH) isoenzymes and Aldehyde Dehydrogenase
      (ALDH) in normal and cancerous bladder cells. METHODS: Class III, IV of ADH and
      total ADH activity were measured by the photometric method and class I, II ADH
      and ALDH activity by the fluorometric method. RESULTS: Significantly higher total
      activity of ADH was found in both, low-grade and high-grade bladder cancer, in
      comparison to healthy tissues. CONCLUSION: The increased activity of total ADH in
      bladder cancer cells may be the cause of metabolic disorders in cancer cells,
      which may intensify carcinogenesis.

PMID- 29381399
TI  - Health literacy, emotionality, scientific evidence: Elements of an effective
      communication in public health.
AB  - The importance of healthcare providers' communication abilities is still
      underestimated. Informing the population on the basis of documented evidence is
      essential but not enough to induce a change in the beliefs of who is doubtful or
      does not accept preventive interventions, such as vaccination. Lining up the
      offer of prevention to the knowledge of the citizens, also improving Health
      Literacy skills, is a critical step toward their empowerment and behavior change.
      The 2017 Erice Declaration was drafted to propose to the Institutions and the
      scientific community the main goals to improve communication and counteract
      Vaccine Hesitancy, at a very critical time, when mandatory vaccination was
      introduced in Italy.

PMID- 29381400
TI  - Knockdown of CXCR4 Inhibits CXCL12-Induced Angiogenesis in HUVECs through
      Downregulation of the MAPK/ERK and PI3K/AKT and the Wnt/beta-Catenin Pathways.
AB  - CXCL12 is an extracellular chemokine binding to cell surface receptor CXCR4. We
      found that activation of CXCL12/CXCR4 axis stimulated angiogenesis in endothelial
      cells. Knockdown of CXCR4 in endothelial cells prevented the branch points of
      angiogenesis. Endothelial cells exposed to CXCL12 presented high level of
      epidermal growth factor receptor (EGFR), vascular endothelial growth factor
      (VEGF), and matrix metalloproteinase MMP-2, but not in CXCR4 knockdown cells.
      Further studies revealed that activation of CXCL12/CXCR4 axis in vascular
      endothelial cells stimulates the angiogenesis through upregulation of the
      MAPK/ERK and PI3K/AKT and Wnt/beta-catenin pathways. Conclusion, downregulation
      of CXCR4 could inhibit angiogenesis in cancer tissues.

PMID- 29381401
TI  - Noninvasive Prenatal Testing of Rare Autosomal Aneuploidies by Semiconductor
      Sequencing.
AB  - Rare autosomal aneuploidies (RAAs) can cause miscarriage or other pregnancy
      complications and lead to inconsistent results of noninvasive prenatal testing
      (NIPT), but many NIPT providers have not yet started to provide related services.
      Our aim was to develop a semiconductor sequencing platform (SSP)-based method for
      detecting RAAs when pregnant women performed NIPT. Fifty-three aneuploidy samples
      with verified karyotyping or array comparative genomic hybridization (aCGH)
      results were collected and subjected to RAAs detection using an SSP to develop a
      method by genomic sequencing. Various trisomies on all chromosomes other than
      chromosomes 17 and 19, four multiple aneusomies, one monosomy and five sex
      chromosome abnormalities were got by our method which can directly identify RAAs
      via a z-score. Then, artificial mixtures of 10% and 5% DNA were created by adding
      fragmented fifty-three tissue samples and used in an NIPT simulation to develop a
      bioinformatics analysis method which can use in NIPT. And the results were in
      accordance with those of karyotyping and aCGH. Therefore, our method has
      potential for use in NIPT. Finally, 23,823 clinical plasma samples were tested to
      verify the performance of our approach. Karyotyping or aCGH was performed on the
      positive clinical samples. In total, 188 of 23,823 clinical samples were positive
      (T2, n = 1; T7, n = 1; T13, n = 15; T18, n = 45; T21, n = 125; and multiple
      aneusomies, n = 1) and verified by karyotyping or aCGH; no sample was a false
      negative. Several false positives were detected, one of which showed maternal
      copy number variation (CNV). One case of multiple aneusomies was caused by a
      maternal tumor. The method developed enables detection of RAAs without increasing
      costs.

PMID- 29381402
TI  - Comparison of baseline ImPACT performance in amateur motocross riders to football
      and basketball athletes.
AB  - PRIMARY OBJECTIVE: The American Motorcyclist Association requires professional
      riders to undergo baseline computerized neurocognitive testing (CNT) using the
      Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test for
      concussion management. It is recommended this practice be expanded to the amateur
      level, but limited research has explored whether baseline testing is necessary
      for youth when normative data is available. This study evaluates the utility of
      baseline testing for amateur riders by comparing their performance to those of
      traditional youth sports comprising normative datasets. DESIGN/METHODS: An cross
      sectional study comparing amateur motocross (N = 100) riders matched by age and
      sex to football (N = 100) and basketball (N = 100) athletes performance on
      baseline ImPACT testing. RESULTS: ANCOVAs revealed a significant medium effect of
      group on measures of visual motor speed (F = 11.25, p < 0.001) and reaction time
      (F = 13.61, p < 0.001). Post hoc analyses revealed that motocross riders were
      significantly slower compared to football and basketball athletes. There were no
      significant differences (p > .05) between sport on measures of memory or
      symptoms. CONCLUSIONS: Youth motocross riders performed significantly slower on
      speed measures compared to football and basketball athletes, providing
      preliminary support for the expansion of baseline ImPACT testing to the amateur
      level.

PMID- 29381403
TI  - Dietary sodium to potassium ratio and the incidence of hypertension and
      cardiovascular disease: A population-based longitudinal study.
AB  - OBJECTIVE: There is an interaction between dietary sodium/potassium intake in the
      pathogenesis of hypertension (HTN) and cardiovascular disease (CVD). The aim of
      this study was to investigate the association of dietary sodium to potassium
      (Na/K) ratio and the risk of HTN and CVD in a general population of Iranian
      adults. METHODS: In this prospective cohort study, adults men and women with
      complete baseline data were selected from among participants of the Tehran Lipid
      and Glucose Study and were followed up for 6.3 years for incidence of HTN and CVD
      outcomes. Dietary sodium and potassium were assessed using a valid and reliable
      168-item food frequency questionnaire. Cox proportional hazards regression models
      were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for
      the association between dietary sodium, potassium and their ratio and risk of
      outcomes. RESULTS: During the study follow-up, 291 (15.1%) and 79 (5.0%) new
      cases of HTN and CVD were identified, respectively. No significant association
      was observed between usual intakes of sodium, potassium and dietary Na/K ratio
      with the incidence of HTN. There was no significant association between dietary
      intakes of sodium and potassium per se and the risk of CVD, whereas when dietary
      sodium to potassium ratio was considered as exposure in the fully-adjusted Cox
      regression model, and participants in the highest compared to lowest tertile had
      a significantly increased risk of CVD (HR = 2.19, 95% CI = 1.16-4.14).
      CONCLUSIONS: Our findings suggest that high dietary Na/K ratio could contribute
      to increased risk of CVD events.

PMID- 29381405
TI  - The influences of cholecystectomy on the circadian rhythms of bile acids as well
      as the enterohepatic transporters and enzymes systems in mice.
AB  - : Bile acids (BAs), the most important endogenous and signaling molecules
      regulate the target transporters and enzymes at transcriptional level,
      participate in a wide variety of processes throughout the entire gastrointestinal
      tract to orchestrate homeostasis in vivo. BAs and their metabolism and
      transportation appear to follow the clear circadian rhythms, and they are
      recently proposed also as the potential chronobiological signals that can affect
      the molecular clock mechanism. Cholecystectomy are believed to affect the
      circadian rhythms of BAs and the relevant enterohepatic transporters and enzymes
      systems and their regulatory signaling pathways, for the reason that the
      circadian cycle of gallbladder filling and emptying play a pivotal role in
      controlling the flow of bile into the intestine and the enterohepatic circulation
      of BAs. Here, in the present study, the circadian rhythms about BAs concentration
      and composition and the mRNA expression of genes involved in BAs transportation,
      metabolism and regulation in liver and ileum of mice with or without gallbladder
      were evaluated. As a result, it has been found that, mice with gallbladder
      exhibited significant and distinct circadian oscillations in BAs concentration,
      mRNA expression of enterohepatic transporters and enzymes systems and farnesoid X
      receptor-mediated regulatory pathways both in liver and ileum during gallbladder
      emptying period (1:00 AM and 1:00 PM), despite food was restricted during these
      periods; the circadian rhythmicity of BAs pool and hepatic and ileal BAs
      diminished but the BAs composition had no significant alteration in liver and
      ileum after cholecystectomy as compared with sham-operated mice; in parallel to
      the alteration of BAs levels in liver and ileum after cholecystectomy, the
      day/night circadian oscillations in the mRNA expression of the relevant
      transporting and metabolic genes and the farnesoid X receptor signaling pathway
      mediated a?oeintestine-livera? regulatory axis also shifted. In conclusion, the
      BAs concentration and the corresponding genes exhibit significant circadian
      rhythms in mice with gallbladder, and the circadian oscillations of most of the
      investigation factors are flattened and altered following by cholecystectomy,
      which could mainly ascribe to the disappearance of the filling and emptying cycle
      of gallbladder and might result in pathological states or drug chronopharmacology
      alternation. We expect that this study would provide a cue for patients with
      cholecystectomy. ABBREVIATIONS: Asbt: apical sodium-dependent bile acids
      transporter; AUC24h: area under the 24-hour BA concentration time curve; BAs:
      bile acids; Bsep: bile salt export pump; beta-MCA: beta-muricholic acid; CA:
      cholic acid; CDCA: chenodeoxycholic acid; Cyp3a11: cytochrome P450 3a11 (human
      CYP3A4); Cyp7a1: cholesterol 7alpha-hydroxylase cytochrome P450 7a1; DCA:
      deoxycholic acid; Fxr: farnesoid X receptor; Fgf15: fibroblast growth factor 15;
      G-: glycine conjugated bile acid; HDCA: hyodesoxycholic acid; LCA: lithocholic
      acid; Mrp2: multidrug resistance-associated protein 2; NDCA: demethylation
      deoxycholic acid; Ntcp: Na+-taurocholate co-transporting polypeptide; Oatp2:
      organic anion transporting polypeptide 2; Ostalpha/beta: heterodimeric organic
      solute transporters alpha and beta; Shp: small heterodimer partner; T-: taurine
      conjugated bile acid; UDCA: ursodeoxycholic acid.

PMID- 29381404
TI  - Agreement in DNA methylation levels from the Illumina 450K array across batches,
      tissues, and time.
AB  - Epigenome-wide association studies (EWAS) have focused primarily on DNA
      methylation as a chemically stable and functional epigenetic modification.
      However, the stability and accuracy of the measurement of methylation in
      different tissues and extraction types is still being actively studied, and the
      longitudinal stability of DNA methylation in commonly studied peripheral tissues
      is of great interest. Here, we used data from two studies, three tissue types,
      and multiple time points to assess the stability of DNA methylation measured with
      the Illumina Infinium HumanMethylation450 BeadChip array. Redundancy analysis
      enabled visual assessment of agreement of replicate samples overall and showed
      good agreement after removing effects of tissue type, age, and sex. At the probe
      level, analysis of variance contrasts separating technical and biological
      replicates clearly showed better agreement between technical replicates versus
      longitudinal samples, and suggested increased stability for buccal cells versus
      blood or blood spots. Intraclass correlations (ICCs) demonstrated that inter
      individual variability is of similar magnitude to within-sample variability at
      many probes; however, as inter-individual variability increased, so did ICC.
      Furthermore, we were able to demonstrate decreasing agreement in methylation
      levels with time, despite a maximal sampling interval of only 576 days. Finally,
      at 6 popular candidate genes, there was a large range of stability across probes.
      Our findings highlight important sources of technical and biological variation in
      DNA methylation across different tissues over time. These data will help to
      inform longitudinal sampling strategies of future EWAS.

PMID- 29381407
TI  - Premature birth and circadian preference in young adulthood: evidence from two
      birth cohorts.
AB  - A preference for eveningness (being a "night owl") and preterm birth (<37 weeks
      of gestation) are associated with similar adversities, such as elevated blood
      pressure, impaired glucose regulation, poorer physical fitness, and lower mood.
      Yet, it remains unclear if and how preterm birth is associated with circadian
      preference. The aim of this study was to assess this association across the whole
      gestation range, using both objective and subjective measurements of circadian
      preference. Circadian preference was measured among 594 young adults (mean age
      24.3 years, SD 1.3) from two cohorts: the ESTER study and the Arvo Ylppo
      Longitudinal Study. We compared 83 participants born early preterm (<34 weeks)
      and 165 late preterm (34 to <37 weeks) with those born at term (>=37 weeks, n =
      346). We also compared very low birth weight (VLBW, <1500 g) participants with
      term-born controls. We obtained objective sleep data with actigraphs that were
      worn for a mean period of 6.8 (SD 1.4) nights. Our primary outcome was sleep
      midpoint during weekdays and weekend. The sleep midpoint is the half-way time
      between falling asleep and waking up, and it represents sleep timing. We also
      investigated subjective chronotype with the Morningness-Eveningness Questionnaire
      (MEQ) in 688 (n = 138/221/329) ESTER participants. The MEQ consists of 19
      questions, which estimates the respondent to be of a "morning", "evening," or
      "intermediate" chronotype, based on the Morningness-Eveningness Score (MES). We
      analyzed the data from the actigraphs and the MES with three linear regression
      models, and analyzed distribution of the chronotype class with Pearson chi2.
      There were no consistent differences across the study groups in sleep midpoint.
      As compared with those born at term, the mean differences in minutes:seconds and
      95% confidence intervals for the sleep midpoint were: early preterm weekdays
      11:47 (-8:34 to 32:08), early preterm weekend 4:14 (-19:45 to 28:13), late
      preterm weekdays -10:28 (-26:16 to 5:21), and late preterm weekend -1:29 (-20:36
      to 17:37). There was no difference in sleep timing between VLBW-participants and
      controls either. The distribution of chronotype in the MEQ among all participants
      was 12.4% morningness, 65.4% intermediate, and 22.2% eveningness. The
      distribution of the subjective chronotype class did not differ between the three
      gestational age groups (p = 0.98). The linear regression models did not show any
      influence of gestational age group or VLBW status on the MES (all p > 0.5). We
      found no consistent differences between adults born early or late preterm and
      those born at term in circadian preference. The earlier circadian preference
      previously observed in those born smallest is unlikely to extend across the whole
      range of preterm birth.

PMID- 29381408
TI  - Monte Carlo simulations used to calculate the energy deposited in the coronary
      artery lumen as a function of iodine concentration and photon energy.
AB  - PURPOSE: To better understand the risks of cumulative medical X-ray
      investigations and the possible causal role of contrast agent on the coronary
      artery wall, the correlation between iodinated contrast media and the increase of
      energy deposited in the coronary artery lumen as a function of iodine
      concentration and photon energy is investigated. MATERIALS AND METHODS: The
      calculations of energy deposition have been performed using Monte Carlo (MC)
      simulation codes, namely PENetration and Energy LOss of Positrons and Electrons
      (PENELOPE) and Monte Carlo N-Particle eXtended (MCNPX). Exposure of a cylinder
      phantom, artery and a metal stent (AISI 316L) to several X-ray photon beams were
      simulated. RESULTS AND DISCUSSION: For the energies used in cardiac imaging the
      energy deposited in the coronary artery lumen increases with the quantity of
      iodine. Monte Carlo calculations indicate a strong dependence of the energy
      enhancement factor (EEF) on photon energy and iodine concentration. The maximum
      value of EEF is equal to 25; this factor is showed for 83 keV and for 400 mg
      Iodine/mL. No significant impact of the stent is observed on the absorbed dose in
      the artery for incident X-ray beams with mean energies of 44, 48, 52 and 55 keV.
      CONCLUSION: A strong correlation was shown between the increase in the
      concentration of iodine and the energy deposited in the coronary artery lumen for
      the energies used in cardiac imaging and over the energy range between 44 and 55
      keV. The data provided by this study could be useful for creating new medical
      imaging protocols to obtain better diagnostic information with a lower level of
      radiation exposure.

PMID- 29381406
TI  - Infection with enteric pathogens Salmonella typhimurium and Citrobacter rodentium
      modulate TGF-beta/Smad signaling pathways in the intestine.
AB  - Salmonella and Citrobacter are gram negative, members of Enterobacteriaceae
      family that are important causative agents of diarrhea and intestinal
      inflammation. TGF-beta1 is a pleiotropic multifunctional cytokine that has been
      implicated in modulating the severity of microbial infections. How these
      pathogens alter the TGF-beta1 signaling pathways in the intestine is largely
      unknown. Streptomycin-pretreated C57BL/6J mouse model colonized with S.
      typhimurium for 8 hours (acute) and 4 days (chronic) infection and FVB/N mice
      infected with C. rodentium for 6 days were utilized. Results demonstrated an
      increase in TGF-beta1 receptor I expression (p<0.05) in S. typhimurium infected
      mouse ileum at both acute and chronic post-infection vs control. This was
      associated with activation of Smad pathways as evidenced by increased
      phosphorylated (p)-Smad2 and p-Smad3 levels in the nucleus. The inhibitory Smad7
      mRNA levels showed a significant up regulation during acute phase of Salmonella
      infection but no change at 4d post-infection. In contrast to Salmonella,
      infection with Citrobacter caused drastic downregulation of TGF receptor I and II
      concomitant with a decrease in levels of Smad 2, 3, 4 and 7 expression in the
      mouse colon. We speculate that increased TGF-beta1 signaling in response to
      Salmonella may be a host compensatory response to promote mucosal healing; while
      C. rodentium decreases TGF-beta1 signaling pathways to promote inflammation and
      contribute to disease pathogenesis. These findings increase our understanding of
      how enteric pathogens subvert specific aspects of the host-cellular pathways to
      cause disease.

PMID- 29381409
TI  - Complete ophthalmoplegia in Ipilmumab and Nivolumab combination treatment for
      metastatic melanoma.
AB  - Ipilimumab and Nivolumab are novel monoclonal antibodies that have recently been
      used successfully for treatment of metastatic melanoma. Ipilimumab is a human
      monoclonal antibody against Cytotoxic T Lymphocyte Antigen 4 (CTLA4) receptor,
      which suppresses T-cell proliferation and stimulates an inflammatory response
      against cancer cells. Nivolumab is an IgG4 monoclonal antibody against the
      cytotoxic T lymphocyte associated programmed death 1 receptor (PD-1). Ipilimumab
      and Nivolumab combination treatment has been shown to induce remission and
      prolong survival in patients with metastatic melanoma. The side effect profile of
      these medications has not been well studied. One entity of the side effects
      reported in the literature is immune-related adverse events (irAEs). There have
      been few case reports where these events were serious and irreversible. In this
      case report, we describe a fatal and severe diffuse panmyositis that involved the
      cardiac, respiratory, and extraocular muscles in a patient with metastatic
      melanoma secondary to combination treatment with Ipilimumab/Nivolumab.

PMID- 29381410
TI  - What Does a Cancer Diagnosis Mean? Public Expectations in a Shifting Therapeutic
      Environment.

PMID- 29381411
TI  - Relationship Between Objective Financial Burden and the Health-Related Quality of
      Life and Mental Health of Patients With Cancer.
AB  - PURPOSE: The high and increasing costs of cancer care can lead to financial
      burden for patients and their families. However, no study has specifically
      examined the association between objective measures of financial burden and the
      health-related quality of life (HRQOL) and psychological health of patients with
      cancer. METHODS: Data on patients with cancer were obtained from the 2010 to 2014
      Medical Expenditure Panel Survey. High financial burden was defined as a ratio of
      annual family out-of-pocket health care expenditures to family income exceeding
      either 10% or 20%. Multivariable linear regressions were used to estimate the
      relationship between high financial burden and patient HRQOL, nonspecific
      psychological distress, and depressed mood. RESULTS: Of 6,799 patients with
      cancer, 15% and 6% experienced high financial burden exceeding 10% and 20% of
      family income, respectively. Compared with those without high financial burden,
      patients with cancer with high financial burden were more likely to have
      significantly lower HRQOL and a greater tendency toward nonspecific psychological
      distress. Higher levels of financial burden were associated with lower HRQOL,
      with a stronger relationship observed with physical health than with mental
      health and a greater tendency toward nonspecific psychological distress.
      Depressed mood was not significantly associated with high financial burden.
      CONCLUSION: High financial burden among patients with cancer was significantly
      associated with lower HRQOL and poor mental health. Along with efforts to reduce
      health care costs for cancer survivors, additional interventions are necessary to
      ensure the HRQOL and psychological health of cancer survivors.

PMID- 29381413
TI  - Effectivity of Biophysical Barriers in Peridural Fibrosis.

PMID- 29381412
TI  - Price of Cancer Care and Its Tax on Quality of Life.

PMID- 29381414
TI  - A simple mathematical method to estimate ammonia emission from in-house
      windrowing of poultry litter.
AB  - In-house windrowing between flocks is an emerging sanitary management practice to
      partially disinfect the built-up litter in broiler houses. However, this practice
      may also increase ammonia (NH3) emission from the litter due to the increase in
      litter temperature. The objectives of this study were to develop mathematical
      models to estimate NH3 emission rates from broiler houses practicing in-house
      windrowing between flocks. Equations to estimate mass-transfer areas form
      different shapes windrowed litter (triangular, rectangular, and semi-cylindrical
      prisms) were developed. Using these equations, the heights of windrows yielding
      the smallest mass-transfer area were estimated. Smaller mass-transfer area is
      preferred as it reduces both emission rates and heat loss. The heights yielding
      the minimum mass-transfer area were 0.8 and 0.5 m for triangular and rectangular
      windrows, respectively. Only one height (0.6 m) was theoretically possible for
      semi-cylindrical windrows because the base and the height were not independent.
      Mass-transfer areas were integrated with published process-based mathematical
      models to estimate the total house NH3 emission rates during in-house windrowing
      of poultry litter. The NH3 emission rate change calculated from the integrated
      model compared well with the observed values except for the very high NH3 initial
      emission rate from mechanically disturbing the litter to form the windrows. This
      approach can be used to conveniently estimate broiler house NH3 emission rates
      during in-house windrowing between flocks by simply measuring litter
      temperatures.

PMID- 29381415
TI  - Attractive Serial Dependence in the Absence of an Explicit Task.
AB  - Attractive serial dependence refers to an adaptive change in the representation
      of sensory information, whereby a current stimulus appears to be similar to a
      previous one. The nature of this phenomenon is controversial, however, as serial
      dependence could arise from biased perceptual representations or from biased
      traces of working memory representation at a decisional stage. Here, we
      demonstrated a neural signature of serial dependence in numerosity perception
      emerging early in the visual processing stream even in the absence of an explicit
      task. Furthermore, a psychophysical experiment revealed that numerosity
      perception is biased by a previously presented stimulus in an attractive way, not
      by repulsive adaptation. These results suggest that serial dependence is a
      perceptual phenomenon starting from early levels of visual processing and
      occurring independently from a decision process, which is consistent with the
      view that these biases smooth out noise from neural signals to establish
      perceptual continuity.

PMID- 29381416
TI  - Removal of fluoride from wastewater using HCl-treated activated alumina in a
      ribbed hydrocyclone separator.
AB  - Excessive fluoride concentration in wastewater is a major health concern
      worldwide. The main objective of wastewater treatment is to allow industrial
      effluents to be disposed of without danger to the human health and the natural
      environment. In this current study, experiments have been conducted to remove
      fluoride from aqueous solution using alumina and HCl (Hydrochloric acid) treated
      activated alumina in a continuous mode. A spiral rib was introduced in the
      cylindrical part of the conventional hydrocyclone to increase the performance,
      and the new hydrocyclone is dubbed as ribbed hydrocyclone. Experiments were
      carried out to analyze the performance of the ribbed hydrocyclone and compared
      the results with the conventional hydrocyclone of the same dimension. The
      efficiency of conventional and ribbed hydrocyclone at a slurry flow rate of 50
      LPM (liter per minute) for the solid concentration of 1.4 wt% were 80% and 93.5%
      respectively. The cut size d50 of the conventional and ribbed hydrocyclone was 18
      um and 13 um respectively at a slurry velocity of 50 LPM. Fluoride removal
      efficiency using alumina and HCl-treated alumina was also investigated in a
      continuous mode by the ribbed hydrocyclone. Maximum fluoride removal efficiency
      was 49.5%, and 80% for alumina and HCl-treated alumina for the initial
      concentration of 10 mg/L at a slurry flow rate of 50 LPM.

PMID- 29381417
TI  - Copper nanoparticles toxicity: Laboratory strains verses environmental bacterial
      isolates.
AB  - Nanoparticles have emerged as significant environmental contaminants and their
      impact has been studied using laboratory strains of bacteria. This study focuses
      on investigating the response of environmental isolate and laboratory strains of
      E. coli to 50 and 100 nm size of copper nanoparticles (CuNPs). The laboratory
      cultures included pathogenic and non-pathogenic strains. The environmental
      isolate and the non-pathogenic E. coli strain showed different inactivation
      patterns. After 2 h exposure to 50 nm CuNPs, the environmental isolate and the
      lab strain of E. coli lost 7.22 and 6.47 log; whereas the reduction of 6.16 and
      6.68 log resulted after exposure to 100 nm CuNPs, respectively. The pathogenic E.
      coli O157:H7 exposed to 50 and 100 nm CuNPs for 2 h resulted in 5.24 and 6.54 log
      reduction, respectively. Although the environmental isolate and the laboratory
      strains of E. coli showed similar inactivation trends; they exhibited different
      toxicity elicitation mechanisms after exposure to the CuNPs. The pathogenic and
      non-pathogenic strains elicited significantly different levels of glutathione
      reductase (GR) activities, an enzyme critical for protection against radicals.
      Similarly, the environmental isolate and the lab strains of E. coli exhibited
      opposite trend in GR activities. These results clearly indicate divergence in the
      toxicity elicitation in the environmental isolate versus the laboratory strains
      from exposure to CuNPs, which highlights the need for an in-depth investigation
      of the impact of NPs on the biological processes and long-term effect of high
      load of NPs on the stability of aquatic and terrestrial ecologies.

PMID- 29381418
TI  - Regulatory T cells (Tregs): A major immune checkpoint to consider in
      combinatorial therapeutic HIV-1 vaccines.
AB  - The field of immunotherapeutics is living an exceptional time as new antibodies
      that take brakes off T-cells and unleash them on tumours are being approved by
      the US-Food and Drug Administration (FDA). For the design and development of an
      HIV-1 therapeutic-vaccine, one would need preferably to shift the balance T
      effectors/T-regulatory cells (Teff/Tregs) towards effectors to improve vaccine
      specific immune-responses. Given the success with the new immune-checkpoint
      blockers (ICB), it is an appropriate time for HIV-1 field to seize this
      opportunity and develop new therapeutic vaccine-strategies that take into
      consideration ICB and other immunomodulators such as cytokines. While the vaccine
      is important to stimulate HIV-1-specific T-cell responses, cytokines will support
      the expansion of the stimulated virus-specific T-cells and ICB will reverse
      exhaustion and unchain cytotoxic T-cells. In this commentary, we will spotlight
      Tregs as another major brake for T-cell immunity and address the main stumbling
      blocks that often blurs HIV-1-specific-Tregs status with regards to their role
      (beneficial or detrimental) and we will recall some proof-of-concept studies
      where therapeutic immunization skewed the HIV-1-specific response from Tregs to
      Teffs which impacts on the magnitude of viral replication. We will also suggest
      some strategies to shift the balance towards Teffs and potentiate HIV-1-specific
      immune-responses.

PMID- 29381420
TI  - Euhaplorchis californiensis Cercariae Exhibit Positive Phototaxis and Negative
      Geotaxis.
AB  - Parasites often use external cues to identify and move toward environments where
      they are likely to encounter suitable hosts. The trematode parasite Euhaplorchis
      californiensis produces cercariae that emerge from California horn snails (
      Cerithideopsis californica [= Cerithidea californica]) to infect California
      killifish ( Fundulus parvipinnis) as second intermediate hosts. Based upon work
      on a congeneric Euhaplorchis species from Florida, and based on the ecology of
      its killifish host, we hypothesized that E. californiensis cercariae in southern
      California estuaries are positively phototactic and negatively geotactic, using
      both sunlight and gravity to guide their movement to the upper water column. To
      distinguish positive phototaxis from negative geotaxis, we first quantified E.
      californiensis movement in response to light along a horizontal plane and
      determined they were positively phototactic. In a second experiment, we
      quantified E. californiensis movement along a vertical plane in response to an
      overhead light, a light from below, or no light. We found that E. californiensis
      exhibit negative geotaxis in the absence of light, but will swim in the direction
      of gravity to move toward a light source from below. Thus, E. californiensis are
      both positively phototactic and negatively geotactic, but cercariae prioritize
      phototactic cues. These results suggest that E. californiensis cercariae
      aggregate in the open water, indicating that the pelagic zone represents an area
      of high infection risk for California killifish hosts.

PMID- 29381419
TI  - Evaluation of collagenase gold plus BP protease in isolating islets from human
      pancreata.
AB  - Selection of enzymes for optimal pancreas digestion is essential for successful
      human islet isolations. The aim of this study was to evaluate the efficacy and
      outcome of using Collagenase Gold plus BP protease (VitaCyte) (n = 8) by
      comparing it to two commercially available enzymes, Liberase MTF C/T (Roche) (n =
      48) and Collagenase NB1/NP (Serva) (n = 15). The isolation outcomes were assessed
      by islet counting, viability, glucose-stimulated oxygen consumption rate (OCR),
      and successful graft-rate following transplantation in diabetic NOD scid mice.
      The pancreas donor characteristics were not significantly different between the
      tested enzyme groups regarding their BMI, pancreas weight, cold ischemia time
      (CIT) and HbA1c. The results show that digested tissue volume was not
      statistically significant between the VitaCyte enzyme (34.25 +/- 5.4 mL) and the
      Roche enzyme (55.25 +/- 3.42 mL, p = 0.073), however, this was significant with
      Serva enzyme (64.07 +/- 7.95 mL, p = 0.020). Interestingly, the islet yields were
      not statistically different between all enzyme groups. Moreover, when islets were
      transplanted into NOD scid mice, the reversal rate of diabetes for the VitaCyte
      enzyme group was similar to all enzyme groups. In conclusion, the effectiveness
      of Collagenase Gold plus BP protease is comparable to the MTF C/T and the
      Collagenase NB1/NP enzymes; the low cost could facilitate the use of more
      pancreata for islet isolations.

PMID- 29381421
TI  - Mild hypothermic culture conditions affect residual host cell protein composition
      post-Protein A chromatography.
AB  - Host cell proteins (HCPs) are endogenous impurities, and their proteolytic and
      binding properties can compromise the integrity, and, hence, the stability and
      efficacy of recombinant therapeutic proteins such as monoclonal antibodies
      (mAbs). Nonetheless, purification of mAbs currently presents a challenge because
      they often co-elute with certain HCP species during the capture step of protein A
      affinity chromatography. A Quality-by-Design (QbD) strategy to overcome this
      challenge involves identifying residual HCPs and tracing their source to the
      harvested cell culture fluid (HCCF) and the corresponding cell culture operating
      parameters. Then, problematic HCPs in HCCF may be reduced by cell engineering or
      culture process optimization. Here, we present experimental results linking cell
      culture temperature and post-protein A residual HCP profile. We had previously
      reported that Chinese hamster ovary cell cultures conducted at standard
      physiological temperature and with a shift to mild hypothermia on day 5 produced
      HCCF of comparable product titer and HCP concentration, but with considerably
      different HCP composition. In this study, we show that differences in HCP variety
      at harvest cascaded to downstream purification where different residual HCPs were
      present in the two sets of samples post-protein A purification. To detect low
      abundant residual HCPs, we designed a looping liquid chromatography-mass
      spectrometry method with continuous expansion of a preferred, exclude, and
      targeted peptide list. Mild hypothermic cultures produced 20% more residual HCP
      species, especially cell membrane proteins, distinct from the control.
      Critically, we identified that half of the potentially immunogenic residual HCP
      species were different between the two sets of samples.

PMID- 29381422
TI  - Hodgkin Lymphoma revealed by epidural spinal cord compression.
AB  - CONTEXT: Hodgkin Lymphoma is rarely diagnosed as spinal cord compression
      syndrome. Caused by an epidural mass, this complication is often encountered in a
      late stage of the disease. We report the case of a 40-year-old man presenting
      with symptoms of low thoracic spinal cord compression due to an epidural tumor on
      the MRI. FINDINGS: Emergent surgery was undertaken on this patient, consisting in
      laminectomy and tumor resection. After surgery, pain relief and mild neurological
      improvement were noticed. The histological study revealed a Hodgkin Lymphoma and
      the patient was referred to chemotherapy and radiotherapy. CONCLUSION: Though
      chemotherapy is the gold standard treatment for Hodgkin Lymphoma, surgical spinal
      decompression may be required in epidural involvement of the disease. Diagnosis
      may be suspected in the presence of lymphadenopathy and general health decay.

PMID- 29381423
TI  - Glenohumeral Internal Rotation Deficit and Risk of Upper Extremity Injury in
      Overhead Athletes: A Meta-Analysis and Systematic Review.
AB  - CONTEXT: Current perception dictates that glenohumeral internal rotation deficit
      (GIRD) is a chronic adaptation that leads to an increased risk of pathologic
      conditions in the dominant shoulder or elbow of overhead athletes. OBJECTIVE: To
      determine whether adaptations in glenohumeral range of motion in overhead
      athletes lead to injuries of the upper extremity, specifically in the shoulder or
      elbow. DATA SOURCES: An electronic database search was performed using Medline,
      Embase, and SportDiscus from 1950 to 2016. The following keywords were used:
      GIRD, glenohumeral internal rotation deficit, glenohumeral deficit, shoulder,
      sport, injury, shoulder joint, baseball, football, racquet sports, volleyball,
      javelin, cricket, athletic injuries, handball, lacrosse, water polo, hammer
      throw, and throwing injury. STUDY SELECTION: Seventeen studies met the inclusion
      criteria for this systematic review. Of those 17 studies, 10 included specific
      range of motion measurements required for inclusion in the meta-analysis. STUDY
      DESIGN: Systematic review and meta-analysis. LEVEL OF EVIDENCE: Level 4. DATA
      EXTRACTION: Data on demographics and methodology as well as shoulder range of
      motion in various planes were collected when possible. The primary outcome of
      interest was upper extremity injury, specifically shoulder or elbow injury.
      RESULTS: The systematic review included 2195 athletes (1889 males, 306 females)
      with a mean age of 20.8 years. Shoulders with GIRD favored an upper extremity
      injury, with a mean difference of 3.11 degrees  (95% CI, -0.13 degrees  to 6.36
      degrees ; P = 0.06). Shoulder total range of motion suggested increased motion
      (mean difference, 2.97 degrees ) correlated with no injury ( P = 0.11), and less
      total motion (mean difference, 1.95 degrees ) favored injury ( P = 0.14).
      External rotational gain also favored injury, with a mean difference of 1.93
      degrees  ( P = 0.07). CONCLUSION: The pooled results of this systematic review
      and meta-analysis did not reach statistical significance for any shoulder motion
      measurement and its correlation to shoulder or elbow injury. Results, though not
      reaching significance, favored injury in overhead athletes with GIRD, as well as
      rotational loss and external rotational gain.

PMID- 29381424
TI  - Spatiotemporal analysis of 3D kinematic asymmetry in professional cycling during
      an incremental test to exhaustion.
AB  - This study investigated the influence of an incremental exercise on bilateral
      asymmetry through the spatio-temporal evolution of 3D joint angular displacement,
      using the Normalized Symmetry Index ([Formula: see text]) and cross-correlation
      methods. Twelve professional cyclists performed an incremental test to
      exhaustion, during which motion capture was used. Results revealed a decrease in
      range of motion between the first and last stages for twelve of the eighteen
      joint rotations, with the highest impact observed for right hip flexion/extension
      (61.8 +/- 4.7 degrees  to 58.8 +/- 4.1 degrees , p < 0.05, ES = 0.68). For both
      stages, significant bilateral differences greater than 10 degrees  were observed
      for hip and knee flexion/extension (p < 0.05, ES>0.90) and ankle and hip
      internal/external rotation (p < 0.05, ES>0.25). Cross-correlation displayed the
      lowest pattern similarities for hip abduction/adduction and the highest
      similarities for knee flexion/extension, ankle plantarflexion/dorsiflexion and
      hip internal/external rotation. The cross-correlation method showed that the
      right leg was mostly ahead of time with respect to the left leg, a trend that was
      accentuated with power output increase. Instantaneous [Formula: see text]
      fluctuated up to 18% throughout the pedalling cycle, with different behaviour
      between the power and recovery phases. This study demonstrated the workload
      effects on side-to-side joint angular pattern similarity.

PMID- 29381425
TI  - A Low-Cost Pulse Generator for Exacerbating Muscle Fiber Detachment Phenotypes in
      Zebrafish.
AB  - Muscle fiber detachment from myoseptal boundaries is a common finding in
      zebrafish models of muscular dystrophies. In some instances, there is a weakening
      of the interaction between muscle fiber and myosepta, which is yet to manifest as
      a fiber detachment phenotype. Therefore, to push the fiber detachment of muscle,
      mutant fish but not their wild-type siblings, beyond their binding threshold, a
      series of small electrical pulses can be applied to the larvae to create a
      maximal force contraction and ultimately fiber detachment. To do this, we built a
      digital pulse generator which delivers four 8 ms 30 V pulses in quick succession,
      and it has the advantage over older analog approaches to pulse generation because
      it improves accuracy and is appreciably less expensive. Our pulse generator
      significantly increases fiber detachment in the laminin-alpha2 deficient,
      congenital muscular dystrophy type 1a (MDC1a) model lama2-/- fish when compared
      with controls.

PMID- 29381426
TI  - Real-Time Cameraless Measurement System Based on Bioelectrical Ventilatory
      Signals to Evaluate Fear and Anxiety.
AB  - Fear and anxiety in fish are generally evaluated by video-based behavioral
      analysis. However, it is difficult to distinguish the psychological state of fish
      exclusively through video analysis, particularly whether the fish are freezing,
      which represents typical fear behavior, or merely resting. We propose a system
      that can measure bioelectrical signals called ventilatory signals and
      simultaneously analyze swimming behavior in real time. Experimental results
      comparing the behavioral analysis of the proposed system and the camera system
      showed a low error level with an average absolute position error of 9.75 +/- 3.12
      mm (about one-third of the body length) and a correlation between swimming speeds
      of r = 0.93 +/- 0.07 (p < 0.01). We also exposed the fish to zebrafish skin
      extracts containing alarm substances that induce fear and anxiety responses to
      evaluate their emotional changes. The results confirmed that this solution
      significantly changed all behavioral and ventilatory signal indices obtained by
      the proposed system (p < 0.01). By combining the behavioral and ventilatory
      signal indices, we could detect fear and anxiety with a discrimination rate of
      83.3% +/- 16.7%. Furthermore, we found that the decreasing fear and anxiety over
      time could be detected according to the peak frequency of the ventilatory
      signals, which cannot be measured through video analysis.

PMID- 29381427
TI  - Early Socioemotional Intervention Mediates Long-Term Effects of Atypical Rearing
      on Structural Covariation in Gray Matter in Adult Chimpanzees.
AB  - Atypical rearing has deleterious effects on chimpanzee behavior during
      development, some of which can be ameliorated with a responsive care intervention
      (RCI). Here, we obtained in vivo magnetic resonance images of adult brains of 27
      chimpanzees given institutional care, with and without RCI, and compared them
      with those of 16 chimpanzees mother-reared from birth. We found significant long
      term rearing effects on structural covariation and gray matter volume,
      specifically in the basal forebrain (i.e., caudate, putamen, nucleus accumbens,
      rectus gyrus, and orbital prefrontal cortex), indicating that RCI prevented brain
      changes due to atypical rearing. A significant correlation between covariation in
      these brain areas and caregiver nurturing, experienced in the first month of
      life, suggests a possible developmental mechanism for the effect of early
      experience on brain networks. We identified an early intervention that prevents
      changes in the basal forebrain that otherwise emerge as a consequence of
      institutionalized rearing without species-typical socioemotional experiences.

PMID- 29381428
TI  - Impact of Multiple Single-Nucleotide Polymorphisms Within mprF on Daptomycin
      Resistance in Staphylococcus aureus.
AB  - A number of single nucleotide polymorphisms (SNPs) within the mprF open reading
      frame (ORF) have been associated with daptomycin-resistance (DAP-R) in
      Staphylococcus aureus. Such SNPs have been found throughout the mprF ORF,
      although there are clearly preferred "hot spots" within this gene frequently
      linked to DAP-R phenotype. These mprF SNPs are often correlated with a gain-in
      function phenotype, either in terms of increased production (synthase activity)
      and/or enhanced translocation (translocase activity) of lysyl
      phosphatidylglycerol (L-PG) within its cell membrane. However, it is unclear if
      multiple hot spot mprF SNPs can accumulate within mprF ORFs and cause additive
      elevations of DAP minimum inhibitory concentrations (MICs). In this study, we
      used a previously well-characterized plasmid complementation system in S. aureus
      Newman DeltamprF mutant to express: (1) single point-mutated forms of mprF ORFs
      cloned from two DAP-R S. aureus strains (mprFS295L or mprFT345A) and (2) dual
      point-mutated forms of mprF ORFs simultaneously harboring SNPs in the central
      bifunctional domain and synthase domain in MprF, respectively (mprFS295L+L826F or
      mprFT345A+L826F). The current study revealed that, although individual hot spot
      point mutations within mprF ORF can recapitulate signature DAP-R-associated
      phenotypes (i.e., increased DAP MICs, enhanced surface positive charge, and
      increased L-PG synthesis), accumulation of such hot spot point mutations
      paradoxically caused reduction in these latter three metrics.

PMID- 29381429
TI  - Status, sources, and human health risk assessment of PAHs via foliar dust from
      different functional areas in Nanjing, China.
AB  - The present study was carried out to assess and understand the potential health
      risk, level of contamination, composition pattern, and sources of urban foliar
      dust in Nanjing City with respect to polycyclic aromatic hydrocarbons (PAHs).
      Five urban functional areas of foliar dust were analysed and the contents of 16
      priority PAHs were determined. Total PAH concentrations in foliar dust ranged
      from 1.77 to 19.02 MUg.g-1, with an average value of 6.98 MUg.g-1. The PAH
      pattern was dominated by four and five-ring PAHs (contributing > 38% of total
      PAHs) in all of the five functional areas. The results indicated that the
      combustion of fossil fuel, coal, and biomass, as well as vehicle traffic
      emissions were the major sources of PAHs. The estimated incremental lifetime
      cancer risk due to PAHs in foliar dust were 8.19 * 10-6, 6.63 * 10-6, and 9.65 *
      10-6 for childhood, adolescence and adulthood, respectively, indicating a high
      risk of cancer from exposure to foliar dust in Nanjing. Our results indicated
      that foliar dust might be a useful indicator of atmospheric PAH pollution.

PMID- 29381430
TI  - Computer Animation Technology in Behavioral Sciences: A Sequential, Automatic,
      and High-Throughput Approach to Quantifying Personality in Zebrafish (Danio
      rerio).
AB  - An emergent field of animal personality necessitates a method for repeated high
      throughput quantification of behavioral traits across contexts. In this study, we
      have developed an automated video stimulus approach to sequentially present
      different contexts relevant to five "personality" traits (exploration, boldness,
      neophobia, aggression, and sociability), successfully quantifying repeatable
      trait measurements in multiple individuals simultaneously. Although our method is
      designed to quantify personality traits in zebrafish, our approach can
      accommodate the quantification of other behaviors, and could be customized for
      other species. All digital materials and detailed protocols are publicly
      available online for researchers to freely use and modify.

PMID- 29381431
TI  - Automated High-Throughput Damage Scoring of Zebrafish Lateral Line Hair Cells
      After Ototoxin Exposure.
AB  - Zebrafish have emerged as a powerful biological system for drug development
      against hearing loss. Zebrafish hair cells, contained within neuromasts along the
      lateral line, can be damaged with exposure to ototoxins, and therefore, pre
      exposure to potentially otoprotective compounds can be a means of identifying
      promising new drug candidates. Unfortunately, anatomical assays of hair cell
      damage are typically low-throughput and labor intensive, requiring trained
      experts to manually score hair cell damage in fluorescence or confocal images. To
      enhance throughput and consistency, our group has developed an automated damage
      scoring algorithm based on machine-learning techniques that produce accurate
      damage scores, eliminate potential operator bias, provide more fidelity in
      determining damage scores that are between two levels, and deliver consistent
      results in a fraction of the time required for manual analysis. The system has
      been validated against trained experts using linear regression, hypothesis
      testing, and the Pearson's correlation coefficient. Furthermore, performance has
      been quantified by measuring mean absolute error for each image and the time
      taken to automatically compute damage scores. Coupling automated analysis of
      zebrafish hair cell damage to behavioral assays for ototoxicity produces a novel
      drug discovery platform for rapid translation of candidate drugs into preclinical
      mammalian models of hearing loss.

PMID- 29381432
TI  - Endoplasmic Reticulum Stress Facilitates the Survival and Proliferation of
      Nucleus Pulposus Cells in TNF-alpha Stimulus by Activating Unfolded Protein
      Response.
AB  - Intervertebral disc (IVD) degeneration is closely related to inflammatory
      cytokines, such as tumor necrosis factor alpha (TNF-alpha). The endoplasmic
      reticulum (ER) serves several important cell functions, which are essential for
      normal cell metabolism and survival. This study aims to clarify the role of ER
      stress and unfolded protein response (UPR) in TNF-alpha-induced biological
      changes in rat nucleus pulposus cells (NPCs) and IVD degeneration. In our
      research, rat NPCs were cultured with different concentrations of TNF-alpha in
      the presence or absence of ER stress inhibitors. Related genes and proteins were
      measured by immunofluorescence staining, quantitative real-time PCR, and Western
      blot analyses to monitor ER stress. Cell proliferation was evaluated by CCK-8
      assay and cyclin D1 expression. Apoptosis was detected by flow cytometry and
      Western blot analyses. Our results showed that TNF-alpha induced the apoptosis of
      some NPCs in the early stage and then accelerated the proliferation of surviving
      cells. In addition, TNF-alpha stimulus upregulated ER stress markers and
      initiated UPR. However, these effects could be reversed by inhibitors, thereby
      reducing cell proliferation and enhancing apoptosis. In conclusion, ER stress
      reinforces the survival and proliferation of NPCs in TNF-alpha stimulus by
      activating UPR signaling, which could be an important therapeutic target in the
      future.

PMID- 29381434
TI  - Effect of Hepatitis B and C Infection on Recruitment for Cancer Clinical Trials.

PMID- 29381433
TI  - Targeting HER2 by Combination Therapies.

PMID- 29381436
TI  - Reply to M. Janakiram et al.

PMID- 29381435
TI  - Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of
      Relapsed or Refractory Multiple Myeloma.
AB  - Purpose Selinexor, a first-in-class, oral, selective exportin 1 (XPO1) inhibitor,
      induces apoptosis in cancer cells through nuclear retention of tumor suppressor
      proteins and the glucocorticoid receptor, along with inhibition of translation of
      oncoprotein mRNAs. We studied selinexor in combination with low-dose
      dexamethasone in patients with multiple myeloma refractory to the most active
      available agents. Patients and Methods This phase II trial evaluated selinexor 80
      mg and dexamethasone 20 mg, both orally and twice weekly, in patients with
      myeloma refractory to bortezomib, carfilzomib, lenalidomide, and pomalidomide
      (quad-refractory disease), with a subset also refractory to an anti-CD38 antibody
      (penta-refractory disease). The primary end point was overall response rate
      (ORR). Results Of 79 patients, 48 had quad-refractory and 31 had penta-refractory
      myeloma. Patients had received a median of seven prior regimens. The ORR was 21%
      and was similar for patients with quad-refractory (21%) and penta-refractory
      (20%) disease. Among patients with high-risk cytogenetics, including t(4;14),
      t(14;16), and del(17p), the ORR was 35% (six of 17 patients). The median duration
      of response was 5 months, and 65% of responding patients were alive at 12 months.
      The most common grade >= 3 adverse events were thrombocytopenia (59%), anemia
      (28%), neutropenia (23%), hyponatremia (22%), leukopenia (15%), and fatigue
      (15%). Dose interruptions for adverse events occurred in 41 patients (52%), dose
      reductions occurred in 29 patients (37%), and treatment discontinuation occurred
      in 14 patients (18%). Conclusion The combination of selinexor and dexamethasone
      has an ORR of 21% in patients with heavily pretreated, refractory myeloma with
      limited therapeutic options.

PMID- 29381437
TI  - Diagnosis and Treatment of 75 Patients with Idiopathic Lobular Granulomatous
      Mastitis.
AB  - Idiopathic granulomatous lobular matitis (IGLM) is a rare non-specific
      inflammatory disease of the breast. Although IGLM is completely benign, it is
      easily confused with cancer due to progressive breast lump with firmly unilateral
      and discrete mass, nipple retraction and sinus formation. Patients with IGLM are
      usually associated with inflammation of the overlying skin. This study aimed to
      investigate the clinical characteristics of IGLM, treatment options and
      prognosis. From January 2010 to February 2015, 75 IGLM patients in our hospital
      were included, with an average age of 35.9 +/- 10.0 (range 21-61) years. Most of
      them were parous. The main clinical characteristic was the presence of a large,
      irregular and painful mass. Hypoechoic lobulated, irregular tubular or oval
      shaped masses were detected by breast gland ultrasound. Ill-defined mass,
      enlarged axillary lymph nodes, asymmetric density, and architectural distortion
      were found by breast molybdenum palladium X-ray. Diagnosis of IGLM was confirmed
      with histological examination. The majority (60/75) of the IGLM patients received
      surgical treatment, including lumpectomy, abscess drainage or mastectomy.
      Antibiotics were used after surgery. The disease recurred in three patients
      during the follow-up period. Our study suggested that IGLM diagnosis more depends
      on CNB and postoperative histopathological examination, and surgery and
      symptomatic treatment can completely remove the lesions, in order to cure the
      disease.

PMID- 29381438
TI  - Analysis of the influence of passenger vehicles front-end design on pedestrian
      lower extremity injuries by means of the LLMS model.
AB  - OBJECTIVE: This work aims at investigating the influence of some front-end design
      parameters of a passenger vehicle on the behavior and damage occurring in the
      human lower limbs when impacted in an accident. METHODS: The analysis is carried
      out by means of finite element analysis using a generic car model for the vehicle
      and the lower limbs model for safety (LLMS) for the purpose of pedestrian safety.
      Considering the pedestrian standardized impact procedure (as in the 2003/12/EC
      Directive), a parametric analysis, through a design of experiments plan, was
      performed. Various material properties, bumper thickness, position of the higher
      and lower bumper beams, and position of pedestrian, were made variable in order
      to identify how they influence the injury occurrence. The injury prediction was
      evaluated from the knee lateral flexion, ligament elongation, and state of stress
      in the bone structure. RESULTS: The results highlighted that the offset between
      the higher and lower bumper beams is the most influential parameter affecting the
      knee ligament response. The influence is smaller or absent considering the other
      responses and the other considered parameters. The stiffness characteristics of
      the bumper are, instead, more notable on the tibia. Even if an optimal value of
      the variables could not be identified trends were detected, with the potential of
      indicating strategies for improvement. CONCLUSIONS: The behavior of a vehicle
      front end in the impact against a pedestrian can be improved optimizing its
      design. The work indicates potential strategies for improvement. In this work,
      each parameter was changed independently one at a time; in future works, the
      interaction between the design parameters could be also investigated. Moreover, a
      similar parametric analysis can be carried out using a standard mechanical
      legform model in order to understand potential diversities or correlations
      between standard tools and human models.

PMID- 29381439
TI  - Efficacy of Corticosteroid Injection for Treatment of Trigger Finger: A Meta
      Analysis of Randomized Controlled Trials.
AB  - PURPOSE: To determine the efficacy and safety of corticosteroid injection for
      trigger finger by performing a meta-analysis of all relevant studies. METHODS:
      PubMed, EMBASE, and Cochrane Library databases were searched for randomized
      controlled trials (RCTs) comparing corticosteroid injection with other treatments
      for trigger finger. Pooled summary estimates for outcomes, including success
      rate, relapse rate, visual analogue score (VAS) and complications, were
      calculated as standardized mean difference (SMD) or relative risk (RR) either on
      a fixed- or random-effect model via Stata 12.0 software. RESULTS: Ten literatures
      involving 806 patients (387 in corticosteroid injection group and 419 in control
      group) were included. Pooled analysis showed there were no differences in the
      success rate, VAS and complications between patients undergoing corticosteroid
      injection and others. However, the relapse rate was significantly higher in
      patients treated with corticosteroid injection than that of other treatments (RR
      = 19.53, 95% CI = 6.23-61.19). Subgroup analysis indicated the efficacy of
      corticosteroid injection was superior to other non-surgical treatments (success
      rate: RR = 1.54, 95% CI = 1.01-2.35), but inferior to surgery (success rate: RR =
      0.55, 95% CI = 0.48-0.63; relapse rate: RR = 21.15, 95% CI = 6.06-73.85; VAS: SMD
      = 3.49, 95% CI = 2.84-4.14). CONCLUSIONS: Corticosteroid injection may be an
      effective strategy for management of trigger finger, although surgery may be
      needed for some patients due to recurrence.

PMID- 29381440
TI  - Dynamic Neural Turing Machine with Continuous and Discrete Addressing Schemes.
AB  - We extend the neural Turing machine (NTM) model into a dynamic neural Turing
      machine (D-NTM) by introducing trainable address vectors. This addressing scheme
      maintains for each memory cell two separate vectors, content and address vectors.
      This allows the D-NTM to learn a wide variety of location-based addressing
      strategies, including both linear and nonlinear ones. We implement the D-NTM with
      both continuous and discrete read and write mechanisms. We investigate the
      mechanisms and effects of learning to read and write into a memory through
      experiments on Facebook bAbI tasks using both a feedforward and GRU controller.
      We provide extensive analysis of our model and compare different variations of
      neural Turing machines on this task. We show that our model outperforms long
      short-term memory and NTM variants. We provide further experimental results on
      the sequential [Formula: see text]MNIST, Stanford Natural Language Inference,
      associative recall, and copy tasks.

PMID- 29381441
TI  - Coexistence of Stochastic Oscillations and Self-Organized Criticality in a
      Neuronal Network: Sandpile Model Application.
AB  - Self-organized criticality (SOC) and stochastic oscillations (SOs) are two
      theoretically contradictory phenomena that are suggested to coexist in the brain.
      Recently it has been shown that an accumulation-release process like sandpile
      dynamics can generate SOC and SOs simultaneously. We considered the effect of the
      network structure on this coexistence and showed that the sandpile dynamics on a
      small-world network can produce two power law regimes along with two groups of
      SOs-two peaks in the power spectrum of the generated signal simultaneously. We
      also showed that external stimuli in the sandpile dynamics do not affect the
      coexistence of SOC and SOs but increase the frequency of SOs, which is consistent
      with our knowledge of the brain.

PMID- 29381442
TI  - Dethroning the Fano Factor: A Flexible, Model-Based Approach to Partitioning
      Neural Variability.
AB  - Neurons in many brain areas exhibit high trial-to-trial variability, with spike
      counts that are overdispersed relative to a Poisson distribution. Recent work
      (Goris, Movshon, & Simoncelli, 2014 ) has proposed to explain this variability in
      terms of a multiplicative interaction between a stochastic gain variable and a
      stimulus-dependent Poisson firing rate, which produces quadratic relationships
      between spike count mean and variance. Here we examine this quadratic assumption
      and propose a more flexible family of models that can account for a more diverse
      set of mean-variance relationships. Our model contains additive gaussian noise
      that is transformed nonlinearly to produce a Poisson spike rate. Different
      choices of the nonlinear function can give rise to qualitatively different mean
      variance relationships, ranging from sublinear to linear to quadratic.
      Intriguingly, a rectified squaring nonlinearity produces a linear mean-variance
      function, corresponding to responses with a constant Fano factor. We describe a
      computationally efficient method for fitting this model to data and demonstrate
      that a majority of neurons in a V1 population are better described by a model
      with a nonquadratic relationship between mean and variance. Finally, we
      demonstrate a practical use of our model via an application to Bayesian adaptive
      stimulus selection in closed-loop neurophysiology experiments, which shows that
      accounting for overdispersion can lead to dramatic improvements in adaptive
      tuning curve estimation.

PMID- 29381443
TI  - Muscle Synergy-Driven Robust Motion Control.
AB  - Humans are able to robustly maintain desired motion and posture under dynamically
      changing circumstances, including novel conditions. To accomplish this, the brain
      needs to optimize the synergistic control between muscles against external
      dynamic factors. However, previous related studies have usually simplified the
      control of multiple muscles using two opposing muscles, which are minimum
      actuators to simulate linear feedback control. As a result, they have been unable
      to analyze how muscle synergy contributes to motion control robustness in a
      biological system. To address this issue, we considered a new muscle synergy
      concept used to optimize the synergy between muscle units against external
      dynamic conditions, including novel conditions. We propose that two main muscle
      control policies synergistically control muscle units to maintain the desired
      motion against external dynamic conditions. Our assumption is based on biological
      evidence regarding the control of multiple muscles via the corticospinal tract.
      One of the policies is the group control policy (GCP), which is used to control
      muscle group units classified based on functional similarities in joint control.
      This policy is used to effectively resist external dynamic circumstances, such as
      disturbances. The individual control policy (ICP) assists the GCP in precisely
      controlling motion by controlling individual muscle units. To validate this
      hypothesis, we simulated the reinforcement of the synergistic actions of the two
      control policies during the reinforcement learning of feedback motion control.
      Using this learning paradigm, the two control policies were synergistically
      combined to result in robust feedback control under novel transient and sustained
      disturbances that did not involve learning. Further, by comparing our data to
      experimental data generated by human subjects under the same conditions as those
      of the simulation, we showed that the proposed synergy concept may be used to
      analyze muscle synergy-driven motion control robustness in humans.

PMID- 29381444
TI  - A Kernel Embedding-Based Approach for Nonstationary Causal Model Inference.
AB  - Although nonstationary data are more common in the real world, most existing
      causal discovery methods do not take nonstationarity into consideration. In this
      letter, we propose a kernel embedding-based approach, ENCI, for nonstationary
      causal model inference where data are collected from multiple domains with
      varying distributions. In ENCI, we transform the complicated relation of a cause
      effect pair into a linear model of variables of which observations correspond to
      the kernel embeddings of the cause-and-effect distributions in different domains.
      In this way, we are able to estimate the causal direction by exploiting the
      causal asymmetry of the transformed linear model. Furthermore, we extend ENCI to
      causal graph discovery for multiple variables by transforming the relations among
      them into a linear nongaussian acyclic model. We show that by exploiting the
      nonstationarity of distributions, both cause-effect pairs and two kinds of causal
      graphs are identifiable under mild conditions. Experiments on synthetic and real
      world data are conducted to justify the efficacy of ENCI over major existing
      methods.

PMID- 29381445
TI  - Robust Modulation of Integrate-and-Fire Models.
AB  - By controlling the state of neuronal populations, neuromodulators ultimately
      affect behavior. A key neuromodulation mechanism is the alteration of neuronal
      excitability via the modulation of ion channel expression. This type of
      neuromodulation is normally studied with conductance-based models, but those
      models are computationally challenging for large-scale network simulations needed
      in population studies. This article studies the modulation properties of the
      multiquadratic integrate-and-fire model, a generalization of the classical
      quadratic integrate-and-fire model. The model is shown to combine the
      computational economy of integrate-and-fire modeling and the physiological
      interpretability of conductance-based modeling. It is therefore a good candidate
      for affordable computational studies of neuromodulation in large networks.

PMID- 29381446
TI  - Estimating a Separably Markov Random Field from Binary Observations.
AB  - A fundamental problem in neuroscience is to characterize the dynamics of spiking
      from the neurons in a circuit that is involved in learning about a stimulus or a
      contingency. A key limitation of current methods to analyze neural spiking data
      is the need to collapse neural activity over time or trials, which may cause the
      loss of information pertinent to understanding the function of a neuron or
      circuit. We introduce a new method that can determine not only the trial-to-trial
      dynamics that accompany the learning of a contingency by a neuron, but also the
      latency of this learning with respect to the onset of a conditioned stimulus. The
      backbone of the method is a separable two-dimensional (2D) random field (RF)
      model of neural spike rasters, in which the joint conditional intensity function
      of a neuron over time and trials depends on two latent Markovian state sequences
      that evolve separately but in parallel. Classical tools to estimate state-space
      models cannot be applied readily to our 2D separable RF model. We develop
      efficient statistical and computational tools to estimate the parameters of the
      separable 2D RF model. We apply these to data collected from neurons in the
      prefrontal cortex in an experiment designed to characterize the neural
      underpinnings of the associative learning of fear in mice. Overall, the separable
      2D RF model provides a detailed, interpretable characterization of the dynamics
      of neural spiking that accompany the learning of a contingency.

PMID- 29381447
TI  - STABILIZED1 as a heat stress-specific splicing factor in Arabidopsis thaliana.
AB  - To overcome high temperature stress, plants have developed transcriptional
      cascades which express a large amount of chaperone proteins called heat shock
      proteins (HSPs). In our recent publication, we reported that STABILIZED1, as an
      U5-snRNP-interacting protein, is involved in the splicing of heat shock factor
      (HSF) and HSP transcripts during high temperature stress. This indicates that not
      only transcriptional regulation, but also post-transcriptional regulation by
      STA1, is essential for the full activation of HSF-HSP cascades and for
      thermotolerance. Here, we observed that the splicing of HSP transcripts was
      induced independent of STA1 at room temperature after heat acclimation,
      indicating that STA1 acts as a high temperature-specific splicing factor for the
      splicing of HSP transcripts. Our findings suggest the molecular mechanism for how
      HSF and HSP transcripts are spliced well under high temperature stress that
      blocks the splicing of overall transcripts.

PMID- 29381448
TI  - Concern for Others Leads to Vicarious Optimism.
AB  - An optimistic learning bias leads people to update their beliefs in response to
      better-than-expected good news but neglect worse-than-expected bad news. Because
      evidence suggests that this bias arises from self-concern, we hypothesized that a
      similar bias may affect beliefs about other people's futures, to the extent that
      people care about others. Here, we demonstrated the phenomenon of vicarious
      optimism and showed that it arises from concern for others. Participants
      predicted the likelihood of unpleasant future events that could happen to either
      themselves or others. In addition to showing an optimistic learning bias for
      events affecting themselves, people showed vicarious optimism when learning about
      events affecting friends and strangers. Vicarious optimism for strangers
      correlated with generosity toward strangers, and experimentally increasing
      concern for strangers amplified vicarious optimism for them. These findings
      suggest that concern for others can bias beliefs about their future welfare and
      that optimism in learning is not restricted to oneself.

PMID- 29381449
TI  - Critical aspects in dog allergen immunotherapy (DAI). May Component Resolved
      Diagnosis (CRD) play a role in predicting the efficacy?
AB  - We hypothesize that a pivotal condition determining the efficacy of dog allergen
      immunotherapy (DAI) might be the mono-sensitization to dog lipocalins (Can f 1-2)
      in individuals not directly or indirectly exposed to other furry animals. In
      fact, the concomitant sensitization to lipocalins and/or albumins, especially in
      those patients directly exposed to furry animals, may potentially stimulate
      patient's airways by inducing persistent inflammation and, thus, clinical
      symptoms. In these conditions, it is likely that DAI alone could be inadequate to
      reduce airway inflammation mediated by inhalation of dog allergens in patients
      with simultaneous exposure to other furry animals. Can f 5 has been found as
      exclusive allergen in about one third of dog-sensitized individuals. Considering
      the presence of different allergenic materials in extract of mammalian origin, it
      is evident that a standard DAI is not likely to be effective in Can f 5 prevalent
      or mono-sensitized individuals. Moreover, we would underline the need of
      collecting detailed information on the possible exposures to furry animals (other
      than the common pets), an information that usually is neglected in clinical
      practice. Furthermore, a detailed clinical history exploring the real
      significance of dog sensitization (mono or poly-sensitization, induction of
      clinical symptoms after exposure etc.) should be performed before prescribing
      DAI. In some patients, with potential high susceptibility to animal allergens,
      the use of CRD is essential to verify the presence of concomitant allergic
      sensitization to lipocalins and/or albumins belonging to other furry animals. The
      availability of CRD introduced the possibility of a better targeted prescription
      of DAI because it might be useful for point out the primary allergens and for the
      exclusion of cross-reactive ones.

PMID- 29381450
TI  - Evidence for Sexual Reproduction: Identification, Frequency, and Spatial
      Distribution of Venturia effusa (Pecan Scab) Mating Type Idiomorphs.
AB  - Venturia effusa (syn. Fusicladium effusum), causal agent of pecan scab, is the
      most prevalent pathogen of pecan (Carya illinoinensis), causing severe yield
      losses in the southeastern United States. V. effusa is currently known only by
      its asexual (conidial) stage. However, the degree and distribution of genetic
      diversity observed within and among populations of V. effusa are typical of a
      sexually reproducing fungal pathogen, and comparable with other dothideomycetes
      with a known sexual stage, including the closely related apple scab pathogen, V.
      inaequalis. Using the mating type (MAT) idiomorphs from V. inaequalis, we
      identified a single MAT gene, MAT1-1-1, in a draft genome of V. effusa. The MAT1
      1-1 locus is flanked by two conserved genes encoding a DNA lyase (APN2) and a
      hypothetical protein. The MAT locus spanning the flanking genes was amplified and
      sequenced from a subset of 14 isolates, of which 7 contained MAT1-1-1 and the
      remaining samples contained MAT1-2-1. A multiplex polymerase chain reaction
      screen was developed to amplify MAT1-1-1, MAT1-2-1, and a conserved reference
      gene encoding beta-tubulin, and used to screen 784 monoconidial isolates of V.
      effusa collected from 11 populations of pecan across the southeastern United
      States. A hierarchical sampling protocol representing region, orchard, and tree
      allowed for analysis of MAT structure at different spatial scales. Analysis of
      this collection revealed the frequency of the MAT idiomorphs is in a 1:1
      equilibrium of MAT1-1:MAT1-2. The apparent equilibrium of the MAT idiomorphs
      provides impetus for a renewed effort to search for the sexual stage of V.
      effusa. [Formula: see text] Copyright (c) 2018 The Author(s). This is an open
      access article distributed under the CC BY-NC-ND 4.0 International license .

PMID- 29381451
TI  - MAPKK Inhibitor U0126 Inhibits Plasmodiophora brassicae Development.
AB  - Mitogen-activated protein kinase (MAPK) cascades play a central role in cellular
      growth, proliferation, and survival. MAPK cascade genes have been extensively
      investigated in model plants, mammals, yeast, and fungi but are not characterized
      in Plasmodiophora brassicae, which causes clubroot disease in cruciferous plants.
      Here, we identified 7 PbMAPK, 3 PbMAPKK, and 9 PbMAPKKK genes in the P. brassicae
      genome. Transcriptional profiling analysis demonstrated that several MAPK, MAPK
      kinase (MAPKK), and MAPK kinase kinase (MAPKKK) genes were preferentially
      expressed in three different zoosporic stages. Based on yeast two-hybrid assays,
      PbMAKKK7 interacted with PbMAKK3 and PbMAKK3 interacted with PbMAK1/PbMAK3. The
      PbMAKKK7-PbMAKK3-PbMAK1/PbMAK3 cascade may be present in P. brassicae. U0126, a
      potent and specific inhibitor of MAPKK, could inhibit the germination of P.
      brassicae resting spores. U0126 was used to treat the resting spores of P.
      brassicae and coinoculate rapeseed, and was proven to significantly relieve the
      severity of clubroot symptoms in the host plant and delay the life cycle of P.
      brassicae. These results suggest that MAPK signaling pathways may play important
      roles in P. brassicae growth, development, and pathogenicity.

PMID- 29381452
TI  - Recommandations de l'Association des urologues du Canada sur le depistage et le
      diagnostic precoce du cancer de la prostate.

PMID- 29381454
TI  - Inaccuracies and omissions in editorial about robotic-assisted prostatectomy.

PMID- 29381453
TI  - Recommendations for followup of stage I and II seminoma: The Princess Margaret
      Cancer Centre approach.
AB  - Testicular seminoma most commonly affects young men and is associated with
      favourable prognosis. Various followup schedules and imaging protocols for
      testicular seminoma have been described without overall consensus. We reviewed
      the literature together with our experience at the Princess Margaret Cancer
      Centre and present an evidence-based followup approach for patients with stage I
      and II seminoma.

PMID- 29381455
TI  - Canadian Urological Association guideline on the care of the normal foreskin and
      neonatal circumcision in Canadian infants (abridged version).

PMID- 29381456
TI  - A prognostic model for stratifying clinical outcomes in chemotherapy-naive
      metastatic castration-resistant prostate cancer patients treated with abiraterone
      acetate.
AB  - INTRODUCTION: Recently, a prognostic index including six risk factors (RFs)
      (unfavourable Eastern Cooperative Oncology Group performance status [ECOG PS],
      presence of liver metastases, short response to luteinizing hormone-releasing
      hormone [LHRH] agonists/antagonists, low albumin, increased alkaline phosphatase
      [ALP] and lactate dehydrogenase [LDH]) was developed from the COU-AA-301 trial in
      post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC)
      patients treated with abiraterone acetate. Our primary objective was to evaluate
      this model in a cohort of chemotherapy-naive mCRPC patients receiving
      abiraterone. METHODS: We identified 197 chemotherapy-naive patients who received
      abiraterone at six BC Cancer Agency centres and who had complete information on
      all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate
      (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA
      RR and survival outcomes were compared using Chi2 test and log-rank test.
      Multivariable Cox proportional hazard analysis was performed to identify RFs
      independently associated with OS. RESULTS: Patients were classified into good (0
      1 RFs), intermediate (2-3 RFs), and poor (4-6 RFs) prognostic groups (33%, 52%,
      and 15%, respectively). For good-, intermediate-, and poor-risk patients, PSA RR
      (>=50% decline) was 60% vs. 42% vs. 40% (p=0.05); median time to PSA progression
      was 7.3 vs. 5.3 vs. 5.0 months (p=0.02); and median OS was 29.4 vs. 13.8 vs. 8.7
      months (p<0.0001). CONCLUSIONS: The six-factor prognostic index model stratifies
      clinical outcomes in chemotherapy-naive mCRPC patients treated with abiraterone.
      Identifying patients at risk of poor outcome is important for informing clinical
      practice and clinical trial design.

PMID- 29381457
TI  - Urology residents on call: Investigating the workload and relevance of calls.
AB  - INTRODUCTION: On-call medical services assumed by residents represent many hours
      of hard work and no studies have documented what it really entails. As part of an
      effort to improve our on-call system, we examined phone calls received by
      residents on call. Our objectives were to evaluate the characteristics of phone
      calls received by residents on call (who, when, why, need to go to the hospital)
      and to determine residents' perception of these calls. We also looked into
      implementing strategies to reduce unnecessary calls. METHODS: We prospectively
      collected information about calls using a standardized reporting form with the
      participation of all residents (10) from a single urology program over two
      periods of four weeks from November 2014 to March 2015. Residents answered pre-
      and post-collecting period questionnaires. RESULTS: A total of 460 calls were
      recorded on 97 on-call days in two on-call lists. There was a mean of 3.5 (median
      3, range 0-12) calls per weeknight and 7.7 (median 6, range 0-23) calls per
      weekend full day. Nintey-three calls (20%) led to the need for bedside evaluation
      and many of these were for new consultations (49%). The majority of calls
      originated from the clinical in-patient ward (49%) and emergency room (29%), and
      nurses (66%) and doctors (23%) most commonly initiated the calls. Calls between
      11:00 pm and 8:00 am represented 13% of all calls. Most of the calls (77%) were
      perceived as relevant or very relevant. Most residents reported at least 80% of
      calls. CONCLUSIONS: Although likely representing an underestimate of the reality,
      we provide a first effort in documenting the call burden of Canadian urology
      residents.

PMID- 29381459
TI  - Assessment of urology postgraduate trainees' competencies in flexible
      ureteroscopic stone extraction.
AB  - INTRODUCTION: We aimed to assess flexible ureteroscopic stone extraction skill of
      urology postgraduate trainees (PGTs) at an Objective Structured Clinical
      Examination (OSCE) and to determine whether previous experience in the operating
      theatre or practice on the simulator correlated with performance. METHODS: After
      obtaining ethics approval, PGTs from postgraduate years (PGYs) 3-5 were recruited
      from all four Quebec urology training programs during an OSCE. After a short
      orientation to the UroMentorTM simulator, PGTs were asked to perform Task 10 for
      15 minutes, where two small stones from the left proximal ureter and renal pelvis
      were extracted using a basket. Competency of PGTs in performing the task was
      assessed using objective assessment from the simulator and subjective evaluations
      using Ureteroscopy-Global Rating Scale (URS-GRS). Simulator performance reports
      and URS-GRS scores were analyzed. RESULTS: Thirty PGTs (9 PGY-3, 11 PGY-4, 10 PGY
      5) participated in this study. PGTs had performed a mean of 55.9 semi-rigid and
      45.7 flexible ureteroscopies prior to the study. Mean URS-GRS score of the
      participants was 20.0+/-4.4. Using norm-referenced method with three experts,
      cutoff score of 19 on the URS-GRS was determined to indicate competency. Sixty
      percent (18/30) of PGTs were competent. All eight PGTs who had practiced on the
      simulator were competent. Previous experience in the operating theatre and PGY
      level did not correlate with performance. CONCLUSIONS: This study confirmed the
      feasibility of incorporating the UroMentor at OSCEs to assess competency of
      urology PGTs in ureteroscopic stone extraction skill. PGTs who practiced on the
      simulator scored significantly higher than those who did not practice; however,
      the software needs to be updated to improve its face validity and to include more
      complex tasks, such as holmium laser lithotripsy. Future studies with larger
      sample sizes and more complex cases are needed to confirm these results.

PMID- 29381460
TI  - Personal prostate-specific antigen screening and treatment choices for localized
      prostate cancer among expert physicians.
AB  - INTRODUCTION: We aimed to determine the personal practices of urologists,
      radiation oncologists, and medical oncologists regarding prostate cancer
      screening and treatment using the physician surrogate method, which seeks to
      identify acceptable healthcare interventions by ascertaining interventions
      physicians select for themselves. METHODS: A hierarchical, contingent survey was
      developed through a consensus involving urologists, medical oncologists, and
      radiation oncologists. It was piloted at the University of Toronto and then
      circulated to urologists, radiation oncologists, and medical oncologists through
      professional medical societies in the U.S., Canada, Central and South America,
      Australia, and New Zealand. The primary outcome was physicians' personal choices
      regarding prostate-specific antigen (PSA) screening and the secondary outcome was
      treatment selection among those diagnosed with prostate cancer. RESULTS: A total
      of 869 respondents provided consent and completed the survey. Of these, there
      were 719 urologists, 89 radiation oncologists, nine medical oncologists, and 53
      undisclosed specialists. Most (784 of 869 respondents; 90%) endorsed past or
      future screening for themselves (among male physicians) or for relatives (among
      female physicians). Among urologists and radiation oncologists making prostate
      cancer treatment decisions, there was a significant correlation between physician
      specialty and the treatment selected (Phi coefficient=0.61; p=0.001).
      CONCLUSIONS: Physicians who routinely treat prostate cancer are likely to
      undertake prostate cancer screening themselves or recommend it for immediate
      family members. Treatment choice is influenced by the well-recognized specialty
      bias.

PMID- 29381461
TI  - Implementing robot-assisted radical prostatectomy - one for all and all for one.

PMID- 29381458
TI  - Canadian Urological Association guideline on the care of the normal foreskin and
      neonatal circumcision in Canadian infants (full version).

PMID- 29381462
TI  - Next-generation prostate cancer risk calculator for primary care physicians.
AB  - INTRODUCTION: Current prostate cancer risk calculators are limited in impact
      because only a probability of having prostate cancer is provided. We developed
      the next generation of prostate cancer risk calculator that incorporates life
      expectancy in order to better evaluate prostate cancer risk in context to a
      patient's age and comorbidity. METHODS: We combined two cohorts to develop the
      new risk calculator. The first was 5638 subjects who all underwent a prostate
      biopsy for prostate cancer detection. The second was 979 men diagnosed with
      prostate cancer with long-term survival data. Two regression models were used to
      create multivariable nomograms and an online prostate cancer risk calculator was
      developed. RESULTS: Of the 5638 patients who underwent a prostate biopsy, 629
      (11%) were diagnosed with aggressive prostate cancer (Gleason Score 7[4+3] or
      more). Of the 979 patients who underwent treatment for prostate cancer, the 10
      year overall survival (OS) was 49.6% (95% confidence interval [CI] 46.6-52.9).
      The first multivariable nomogram for cancer risk had a concordance index of 0.74
      (95% CI 0.72, 0.76), and the second nomogram to predict survival had a
      concordance index of 0.71 (95% CI 0.69-0.72). The next-generation prostate cancer
      risk calculator was developed online and is available at:
      http://riskcalc.org/ProstateCA_Screen_Tool. CONCLUSIONS: We have developed the
      next-generation prostate cancer risk calculator that incorporates a patient's
      life expectancy based on age and comorbidity. This approach will better evaluate
      prostate cancer risk. Future studies examining other populations will be needed
      for validation.

PMID- 29381464
TI  - The fate of the foreskin.

PMID- 29381465
TI  - Pitfalls of prioritizing cost-effectiveness in the assessment of medical
      innovation.

PMID- 29381463
TI  - Long-term patient outcomes from the first year of a robotic surgery program using
      multi-surgeon implementation.
AB  - INTRODUCTION: There is concern that surgical quality initially declines during
      the learning phase of robotic surgery. At our institution, we used a multi
      surgeon programmatic approach to the introduction of robotic surgery. The purpose
      of this study was to evaluate outcomes of patients treated during the first year
      of our program. METHODS: This is a historical cohort of all radical prostatectomy
      patients during a one-year period. Baseline, perioperative, and long-term
      followup data were prospectively and retrospectively collected. Treatment failure
      was a composite of any postoperative radiation, androgen-deprivation, or prostate
      specific antigen (PSA) >=0.2. RESULTS: During the study period, 225 radical
      prostatectomy procedures were performed (104 robotic and 121 open). Baseline
      characteristics were similar between groups (p>0.05). All patients were continent
      and 74% were potent prior to surgery. Mean estimated blood loss (280 cc vs. 760
      cc; p<0.001) and blood transfusion (0% vs. 8.3%; p=0.002) was lower in the
      robotic cohort. Non-transfusion complications were similar between groups (13%
      vs. 12%; p=0.7). Mean hospital stay was shorter in the robotic cohort (1.4 vs.
      2.5 days). There was no difference in overall positive margin rate (38% vs. 43%;
      p=0.4) or treatment failure at a median followup of 3.5 years (p=0.4).
      Robotically treated patients were more often continent (89% vs. 77%; p=0.02) and
      potent (48% vs. 32%; p=0.02). CONCLUSIONS: Using an inclusive multi-surgeon
      approach, robotic pros-tatectomy was introduced safely at a Canadian academic
      institution.

PMID- 29381467
TI  - The future of urology in Canada.

PMID- 29381466
TI  - Functional and oncological outcomes of salvage external beam radiotherapy
      following robot-assisted radical prostatectomy in a Canadian cohort.
AB  - INTRODUCTION: We sought to determine the impact of salvage radio-therapy (SRT) on
      oncological and functional outcomes of patients with prostate cancer after
      biochemical recurrence (BCR) following robot-assisted radical prostatectomy
      (RARP). METHODS: Data of 70 patients with prostate cancer treated with SRT after
      developing BCR were retrospectively analyzed from a prospectively collected RARP
      database of 740 men. Oncological (prostate-specific antigen [PSA]) and functional
      (pads/day, International Prostate Symptom Score [IPSS], and Sexual Health
      Inventory for Men [SHIM]) outcomes were reported at six, 12, and 24 months after
      RT and adjusted for pre-SRT status. RESULTS: Men who underwent SRT had a mean
      age, PSA, and time from radical prostatectomy (RP) to RT of 61.8 years (60.1
      63.6), 0.5 ng/ml (0.2-0.8), and 458 days (307-747), respectively. Freedom from
      biochemical failure (FFBF) post-SRT, defined as a PSA nadir <0.2 ng/mL, was
      observed in 89%, 93%, and 81%, at six, 12, and 24 months, respectively.
      Undetectable PSA was observed in 14%, 35%, and 40% at the same time points,
      respectively. There was no significant difference in urinary continence post-SRT
      (p=0.56). Rate of strict continence (0 pads/day) was 71% at 24 months compared to
      78% pre-SRT. Mean IPSS at six, 12, and 24 months was 3.4, 3.6, and 3.6,
      respectively compared to pre-RT score of 3.3 (p=0.61). The mean SHIM score pre
      SRT was comparable at all time points following treatment (p=0.86). CONCLUSIONS:
      In this unique Canadian experience, it appears that early SRT is highly effective
      for the treatment of BCR following RARP with little impact on urinary continence
      and potency outcomes.

PMID- 29381468
TI  - Prostate cancer screening among family physicians in Ontario: An update on
      attitudes and current practice.
AB  - INTRODUCTION: This study serves as an update of prostate cancer screening
      practices among family physicians in Ontario, Canada. Since this population was
      first surveyed in 2010, the Canadian Task Force on Preventive Health Care
      (CTFPHC) and the United States Preventive Services Task Force (USPSTF) released
      recommendations against prostate cancer screening. METHODS: An online survey was
      developed through input from urologists and family practitioners. It was
      distributed via email to all members of the Ontario Medical Association's Section
      on General and Family practice (11 657 family physicians). A reminder email was
      sent at two weeks and the survey remained active for one month. RESULTS: A total
      of 1880 family physicians completed surveys (response rate 16.1%). Overall, 80.4%
      offered prostate cancer screening compared to 91.7% when surveyed in 2010.
      Physicians new to practice (two years or less) were the most likely to not offer
      screening (24.6%). A combination of digital rectal exam (DRE) and prostate
      specific antigen (PSA) remained the most common form of screening (58.3%).
      Following the release of the CTFPHC recommendations, 45.6% of respondents said
      they now screen fewer patients. Participants were less familiar with national
      urological society guidelines compared to task force recommendations. The
      majority (72.6%) of respondents feel PSA screening leads to overdiagnosis and
      treatment. Those surveyed remained split with respect to PSA utility.
      CONCLUSIONS: Data suggest a decline in screening practices since 2010, with newer
      graduates less likely to offer screening. CFTPHC and USPSTF recommendations had
      the greatest impact on clinical practice. Those surveyed were divided with
      respect to PSA utility. Some additional considerations to PSA screening in the
      primary care setting, including patient-driven factors, were not captured by our
      concise survey.

PMID- 29381469
TI  - A pragmatic bottom-up approach to harmonize the units of clinical chemistry tests
      among Belgian clinical laboratories, focusing on immunoassays.
AB  - BACKGROUND: Harmonization of units is an important step to improve the
      comparability of clinical chemistry results, but few examples exist of successful
      harmonization efforts. We present the results of a pragmatic approach that was
      implemented in Belgium from 2012. METHODS: After a large consultation and
      information of stakeholders, preferred units were proposed for 140 assays,
      including the 23 immunoassays discussed in more detail here. The change occurred
      in two phases, first involving assays for which there was no change in the
      numerical result, then changes involving a change in numerical results.
      Laboratories were invited to participate in this harmonization on a voluntary
      basis. The project was based on a bottom-up approach, large consultation and the
      pragmatic choice of the proposed units, including conventional and SI units.
      RESULTS: The large heterogeneity of units was drastically reduced; adoption of
      the preferred units increased from 3% (insulin) - 45% (HCG) to 70% (insulin) -
      96% (LH and FSH). Adoption of the preferred units was higher if it involved no
      change in numerical values (90%) than when there was a change (76%). CONCLUSIONS:
      We believe that the harmonization effort has reached its goals. Without aiming at
      implementing SI units for all parameters, our strategy was successful with a
      large majority of the laboratories switching to the proposed units. Moreover, the
      harmonization program is still progressing, with additional laboratories
      converting to the consensus units.

PMID- 29381470
TI  - Obese phenotype and natriuretic peptides in patients with heart failure with
      preserved ejection fraction.
AB  - The results of several recent experimental studies using animal models and
      clinical trials suggested that obesity is not merely an epiphenomenon or a
      prominent comorbidity in patients with heart failure (HF). Indeed, recent studies
      suggest that obesity is intimately involved in the pathogenesis of HF with
      preserved ejection fraction (HFpEF). The most recent studies indicate that
      approximately 50% of HF patients have HFpEF. As standard pharmacological
      treatment usually shows only a weak or even neutral effect on primary outcomes in
      patients with HFpEF, treatment strategies targeted to specific groups of HFpEF
      patients, such as those with obesity, may increase the likelihood of reaching
      substantial clinical benefit. Considering the well-known inverse relationship
      between body mass index (BMI) values and B-type natriuretic peptide (BNP) levels,
      it is theoretically conceivable that the measurement of natriuretic peptides,
      using cutoff values adjusted for age and BMI, should increase diagnostic and
      prognostic accuracy in HFpEF patients. However, further experimental studies and
      clinical trials are needed to differentiate and better understand specific
      mechanisms of the various HFpEF phenotypes, including obese HFpEF.

PMID- 29381471
TI  - Assessment of bone turnover in osteoporosis: harmonization of the total testing
      process.

PMID- 29381473
TI  - Low dose aspirin for preventing fetal growth restriction: a randomised trial.

PMID- 29381472
TI  - Chromatographic fingerprint analysis, antioxidant properties, and inhibition of
      cholinergic enzymes (acetylcholinesterase and butyrylcholinesterase) of phenolic
      extracts from Irvingia gabonensis (Aubry-Lecomte ex O'Rorke) Baill bark.
AB  - BACKGROUND: Irvingia gabonensis stem bark is a medicinal plant used in most parts
      of Africa to manage a number of ailments including neurodegenerative diseases
      that occur without scientific basis. This work characterized the phenolic
      composition, evaluated the cholinergic enzymes (acetylcholinesterase, AChE and
      butyrylcholinesterase, BChE) inhibition, and assessed the antioxidant activity of
      phenolic extracts from I. gabonensis (Aubry-Lecomte ex O'Rorke) Baill bark.
      METHODS: Total phenol and flavonoids content was evaluated in addition to
      antioxidant activity as shown by Fe2+ chelation, 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical scavenging ability, and 2,2-azino-bis-(3-ethylbenthiazoline-6
      sulfonic acid) (ABTS) radical scavenging ability. Inhibitory activities on AChE
      and BChE were evaluated. RESULTS: The extract was found to be rich in phenolic
      acid (ellagic acid) and flavonoids (quercetrin, kaempferol, and apigenin). The
      phenolic extracts displayed DPPH radical scavenging ability (IC50=19.98 MUg/mL),
      ABTS radical scavenging ability (IC50=18.25 MUg/mL), iron chelation (IC50=113.10
      MUg/mL), and reducing power (Fe3+ to Fe2+) (5.94 mg ascorbic acid equivalent/100
      g). Extracts of I. gabonensis inhibited AChE (IC50=32.90 MUg/mL) and BChE
      (IC50=41.50 MUg/mL) activities in concentration-dependent manner. CONCLUSIONS:
      Hence, possible mechanism through which the stem bark executes their anti
      Alzheimer's disease activity might be by inhibiting cholinesterase activities in
      addition to suppressing oxidative-stress-induced neurodegeneration.

PMID- 29381474
TI  - Professionally responsible management of gynecologic cancer in pregnancy when
      clinical resources are unavoidably limited.

PMID- 29381476
TI  - Tests for comparison of multiple endpoints with application to omics data.
AB  - In biomedical research, multiple endpoints are commonly analyzed in "omics"
      fields like genomics, proteomics and metabolomics. Traditional methods designed
      for low-dimensional data either perform poorly or are not applicable when
      analyzing high-dimensional data whose dimension is generally similar to, or even
      much larger than, the number of subjects. The complex biochemical interplay
      between hundreds (or thousands) of endpoints is reflected by complex dependence
      relations. The aim of the paper is to propose tests that are very suitable for
      analyzing omics data because they do not require the normality assumption, are
      powerful also for small sample sizes, in the presence of complex dependence
      relations among endpoints, and when the number of endpoints is much larger than
      the number of subjects. Unbiasedness and consistency of the tests are proved and
      their size and power are assessed numerically. It is shown that the proposed
      approach based on the nonparametric combination of dependent interpoint distance
      tests is very effective. Applications to genomics and metabolomics are discussed.

PMID- 29381477
TI  - Sputtered Si and Mg doped hydroxyapatite for biomedical applications.
AB  - Hydroxyapatite (HAP) coatings are applied on metallic implant materials to
      combine mechanical properties of metallic material with bioactivity abilities of
      HAP ceramic. In this study, HAP coatings with additions of Si and Mg are proposed
      to be deposited on Ti6Al4V substrates by RF magnetron sputtering. Chemical
      bonding, morphology, topography and corrosion resistance in simulated body fluids
      (SBF) of the coatings were investigated. Additionally, mechanical and biological
      properties of the coatings were evaluated. It was found that the addition of Si
      and Mg does not influence the formation of a HAP phase. All the coatings
      exhibited smooth surface and uniform growth, without defects or cracks. Both
      hardness and elastic modulus of the coated samples decrease with Mg addition in
      the HAP-Si structure. Both Mg and Si addition into HAP coatings were found to
      enhance the corrosion resistance of the Ti6Al4V alloy in the SBF solution.
      Coatings with low Mg content exhibited better corrosion performance. All the
      coatings investigated were biocompatible, as demonstrated by SaOS-2 bone cell
      attachment and growth. However, cell proliferation and morphology were inferior
      on samples with the highest Mg content.

PMID- 29381475
TI  - The role of nutrition in influencing mechanisms involved in environmentally
      mediated diseases.
AB  - Human exposure to environmental contaminants such as persistent chlorinated
      organics, heavy metals, pesticides, phthalates, flame retardants, electronic
      waste and airborne pollutants around the world, and especially in Southeast Asian
      regions, are significant and require urgent attention. Given this widespread
      contamination and abundance of such toxins as persistent organic pollutants
      (POPs) in the ecosystem, it is unlikely that remediation alone will be sufficient
      to address the health impacts associated with this exposure. Furthermore, we must
      assume that the impact on health of some of these contaminants results in
      populations with extraordinary vulnerabilities to disease risks. Further
      exacerbating risk; infectious diseases, poverty and malnutrition are common in
      the Southeast Asian regions of the world. Thus, exploring preventive measures of
      environmental exposure and disease risk through new paradigms of environmental
      toxicology, optimal and/or healthful nutrition and health is essential. For
      example, folic acid supplementation can lower blood arsenic levels, and plant
      derived bioactive nutrients can lower cardiovascular and cancer risks linked to
      pollutant exposure. Data also indicate that diets enriched with bioactive food
      components such as polyphenols and omega-3 polyunsaturated fatty acids can
      prevent or decrease toxicant-induced inflammation. Thus, consuming healthy diets
      that exhibit high levels of antioxidant and anti-inflammatory properties, is a
      meaningful way to reduce the vulnerability to non-communicable diseases linked to
      environmental toxic insults. This nutritional paradigm in environmental
      toxicology requires further study in order to improve our understanding of the
      relationship between nutrition or other lifestyle modifications and toxicant
      induced diseases. Understanding mechanistic relationships between nutritional
      modulation of environmental toxicants and susceptibility to disease development
      are important for both cumulative risk assessment and the design and
      implementation of future public health programs and behavioral interventions.

PMID- 29381478
TI  - Ultrathin MoS2-coated Ag@Si nanosphere arrays as an efficient and stable
      photocathode for solar-driven hydrogen production.
AB  - Solar-driven photoelectrochemical (PEC) water splitting has attracted a great
      deal of attention recently. Silicon (Si) is an ideal light absorber for solar
      energy conversion. However, the poor stability and inefficient surface catalysis
      of Si photocathodes for the hydrogen evolution reaction (HER) have remained key
      challenges. Alternatively, MoS2 has been reported to exhibit excellent catalysis
      performance if sufficient active sites for the HER are available. Here, ultrathin
      MoS2 nanoflakes are directly synthesized to coat arrays of Ag-core Si-shell
      nanospheres (Ag@Si NSs) by using chemical vapor deposition. Due to the high
      surface area ratio and large curvature of these NSs, the as-grown MoS2 nanoflakes
      can accommodate more active sites. In addition, the high-quality coating of MoS2
      nanoflakes on the Ag@Si NSs protects the photocathode from damage during the PEC
      reaction. An photocurrent density of 33.3 mA cm-2 at a voltage of -0.4 V is
      obtained versus the reversible hydrogen electrode. The as-prepared nanostructure
      as a hydrogen photocathode is evidenced to have high stability over 12 h PEC
      performance. This work opens up opportunities for composite photocathodes with
      high activity and stability using cheap and stable co-catalysts.

PMID- 29381479
TI  - Mechanical responses of a-axis GaN nanowires under axial loads.
AB  - Gallium nitride (GaN) nanowires (NWs) hold technological significance as
      functional components in emergent nano-piezotronics. However, the examination of
      their mechanical responses, especially the mechanistic understanding of behavior
      beyond elasticity (at failure) remains limited due to the constraints of in situ
      experimentation. We therefore performed simulations of the molecular dynamics
      (MD) of the mechanical behavior of [Formula: see text]-oriented GaN NWs subjected
      to tension or compression loading until failure. The mechanical properties and
      critical deformation processes are characterized in relation to NW sizes and
      loading conditions. Detailed examinations revealed that the failure mechanisms
      are size-dependent and controlled by the dislocation mobility on shuffle-set
      pyramidal planes. The size dependence of the elastic behavior is also examined in
      terms of the surface structure determined modification of Young's modulus. In
      addition, a comparison with c-axis NWs is made to show how size-effect trends
      vary with the growth orientation of NWs.

PMID- 29381480
TI  - Awareness about medico legal aspects and Consumer Protection Act among dentists.
AB  - BACKGROUND: The practice of medicine in India has undergone considerable change
      affecting delivery of health in both positive and negative directions. As a
      result, there was a growing feeling that medical treatment should be made
      accountable and this led to doctors and dentists becoming subject to the process
      of law. Patients have become more aware of their right to compensation and as a
      consequence doctors and dentists should be knowledgeable about the laws that
      govern them. AIMS AND OBJECTIVES: To assess the awareness about Medico legal
      aspects and Consumer Protection Act [CPA] among Dental professionals. MATERIALS
      AND METHODS: A self-structured validated questionnaire comprising of 20 questions
      related to medico legal aspects and CPA was designed. A total of 450 dental
      professionals were surveyed from 4 prime dental institutions in Chennai, India.
      Of the 450 professionals that were surveyed 150 were MDS faculty, 150 were BDS
      faculty and 150 were PG students. The data was subjected to SPSS, version 16 and
      statistically analysed using Chi square test and Fisher's exact test. A- p value
      less than 0.05 was considered to be statistically significant. RESULTS: BDS
      faculty, MDS faculty and PG students were found to possess similar level of
      understanding and there was no significant difference between the groups.
      Knowledge was found to be equal between male and female dentists. The young
      practitioners were found to be more informed about CPA than the senior
      practitioners. CONCLUSIONS: It was found that most of the participants were aware
      of relevant Medico legal aspects, but were less aware of CPA. This study
      emphasises the need for education relevant to Medico legal aspects and CPA for
      dental professionals.

PMID- 29381481
TI  - Sex prediction from morphometric palatal rugae measures.
AB  - : While abundant research has been conducted on palatal rugae (PR), the
      literature pertaining to the sex dimorphism of the palatal rugae and their use
      for sex prediction is inconclusive. Moreover, palatal rugae have been classified
      into categories based on length, shape, direction and unification but accurate
      rugal morphometric linear and angular measurements have not yet been reported.
      OBJECTIVE: The aims of this study were to -1- assess the dimensions and bilateral
      symmetry of the first three palatal rugae in an adult population and -2- explore
      sex dimorphism and the ability to predict sex from palatal rugae measurements.
      MATERIALS AND METHODS: The maxillary dental casts of 252 non-growing subjects
      (119 males, 130 females, mean age 25.6 +/- 7.7 years) were scanned using a laser
      system (Perceptron ScanWorks(r) V5). Angular and linear transverse and
      anteroposteior measures of the first three palatal rugae were recorded.
      Independent samples t-tests and paired samples t-tests were used to test for side
      related differences and sex dimorphism. Multiple logistic regression was employed
      to model sex using associated palatal rugae measures. RESULTS: Palatal rugae
      exhibited lateral asymmetry in the majority of bilateral measures. Males
      presented with larger values for 9 out of 28 parameters. Four linear rugae
      measurements and one angular measurement together correctly classified 71.4% of
      the subjects in their true gender. CONCLUSIONS: Morphometric palatal rugae
      measurements demonstrated promising usefulness in sex prediction. Recording
      morphometric linear and angular measures is recommended as an adjunct to the
      commonly used classification based on the shapes of rugae.

PMID- 29381482
TI  - Palatal rugae morphology in an adult mediterranean population.
AB  - BACKGROUND: The use of the palatal rugae in forensic odontology is based on their
      unique and individual characteristics. Few studies have assessed the palatal
      rugae in Mediterranean populations and none in the Lebanese population.
      OBJECTIVE: Assess the shape and other morphological features of the palatal rugae
      in a Lebanese adult population, and compare them with reported similar features
      in other populations. MATERIALS AND METHODS: Rugae characteristics were assessed
      on the maxillary dental casts of 217 non-growing subjects (95 males, 122 females,
      age 25.5 +/- 7.6 years) according to guidelines established by Thomas and Kotze
      (1983) and Lysell (1955). The overall number of rugae and numbers of primary
      rugae (> 5mm in length), secondary rugae (3-5mm) and fragmentary rugae (2-3mm) on
      either side were recorded. Rugae were classified according to shape, direction
      and presence of unification. Z-tests were used to compare the proportions between
      right and left sides and between genders. The mean numbers of rugae in each
      category were compared with independent samples t-tests between males and
      females; paired samples t-tests were employed to compare mean numbers of rugae in
      each category between right and left sides. The data were compared with published
      reports on other Mediterranean cohorts. RESULTS: The average number of rugae was
      7.7 per individual, 3.81 on the right and 3.89 on the left. Curved, wavy and
      straight rugae patterns were equally common (one third each). The spatial
      direction of most rugae (49.3%) was backward. Circular, non-specific and
      convergent rugae were rare (< 2% each). Rugae numbers (total, primary, secondary,
      fragmentary) were symmetrical but shape, direction and the occurrence of
      convergence were asymmetrical (p < 0.05). None of the examined characteristics
      showed gender dimorphism. Tabulated comparisons disclosed the equality of rugae
      patterns as major differences with findings from other Mediterranean studies.
      CONCLUSIONS: The palatal rugae in the Lebanese population display shape distinct
      from other reported Mediterranean and non-Caucasian populations. Studies in large
      samples and primary comparisons with other Mediterranean populations are
      warranted.

PMID- 29381483
TI  - Association among geometric configurations of palatal rugae.
AB  - BACKGROUND: The associations between the length and morphological shape-related
      characteristics of palatal rugae have not been fully explored. OBJECTIVE: We
      aimed to assess the possible association among various geometric configurations
      of the palatal rugae in an adult population. MATERIALS AND METHODS: The maxillary
      dental casts of 217 non-growing subjects (95 males, 122 females, mean age 25.5+/
      7.6 years) were scanned (laser scanning system Perceptron ScanWorks(r) V5) and
      digitized for linear measurements. The casts were also surveyed for visual
      categorization into curved, wavy, straight and other topographical forms, along
      with spatial direction of the rugae and the presence of unification. The rugae
      were categorized as primary, secondary, and fragmentary based on their lengths (>
      5mm, 2-3mm, < 2mm, respectively). Chi square and one-way ANOVA and post-hoc tests
      were used to compare the palatal rugae groupings. RESULTS: Primary and backward
      directed rugae prevailed in the total sample (84.7% and 49.3%, respectively).
      Wavy form was dominant among primary lengths, while straight form was associated
      with the shorter secondary and fragmentary groups (p=0.0042). Absence of
      unification was the norm (88.8%). CONCLUSIONS: Associations of length and shape
      characteristics among palatal rugae combine wavy patterns with increased length,
      and straight forms with shorter folds. These features contribute to the
      definition of ruga individuality in combination rather than separately.

PMID- 29381484
TI  - Hypoglycemia unawareness in type 1 diabetes suppresses brain responses to
      hypoglycemia.
AB  - BACKGROUND: Among nondiabetic individuals, mild glucose decrements alter brain
      activity in regions linked to reward, motivation, and executive control. Whether
      these effects differ in type 1 diabetes mellitus (T1DM) patients with and without
      hypoglycemia awareness remains unclear. METHODS: Forty-two individuals (13
      healthy control [HC] subjects, 16 T1DM individuals with hypoglycemia awareness
      [T1DM-Aware], and 13 T1DM individuals with hypoglycemia unawareness [T1DM
      Unaware]) underwent blood oxygen level-dependent functional MRI brain imaging
      during a 2-step hyperinsulinemic euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl)
      clamp for assessment of neural responses to mild hypoglycemia. RESULTS: Mild
      hypoglycemia in HC subjects altered activity in the caudate, insula, prefrontal
      cortex, and angular gyrus, whereas T1DM-Aware subjects showed no caudate and
      insula changes, but showed altered activation patterns in the prefrontal cortex
      and angular gyrus. Most strikingly, in direct contrast to HC and T1DM-Aware
      subjects, T1DM-Unaware subjects failed to show any hypoglycemia-induced changes
      in brain activity. These findings were also associated with blunted hormonal
      counterregulatory responses and hypoglycemia symptom scores during mild
      hypoglycemia. CONCLUSION: In T1DM, and in particular T1DM-Unaware patients, there
      is a progressive blunting of brain responses in cortico-striatal and fronto
      parietal neurocircuits in response to mild-moderate hypoglycemia. These findings
      have implications for understanding why individuals with impaired hypoglycemia
      awareness fail to respond appropriately to falling blood glucose levels. FUNDING:
      This study was supported in part by NIH grants R01DK020495, P30 DK045735,
      K23DK109284, K08AA023545. The Yale Center for Clinical Investigation is supported
      by an NIH Clinical Translational Science Award (UL1 RR024139).

PMID- 29381486
TI  - Effect of a Quality Improvement Project to Reduce Noise in a Pediatric Unit.
AB  - PURPOSE: Noise levels remain high in clinical settings, which may result in
      stress and sleep disruption, and can lead to immunosuppression, delayed healing,
      confusion, disorientation, delusions, and increased length of hospital stay. The
      purpose of this quality improvement project was to assess effects of a
      multidisciplinary noise reduction program on a pediatric unit in an acute care
      hospital in a developing country. METHODS: A quality improvement project was
      carried out over 15 months in a pediatric unit. A three-phase study was conducted
      where the first phase included obtaining patient satisfaction ratings and
      recording sound levels, the second phase included implementing a noise reduction
      program and designing a noise detector machine, and the third phase included
      obtaining patient satisfaction data and recording noise levels over a 1-year
      period. RESULTS: There was a significant decrease in noise of 8 A-weighted
      decibels when comparing the values before and after implementing the quality
      improvement project at t = 6.44, p < 0.000. There was no significant difference
      in patient satisfaction ratings. CLINICAL IMPLICATIONS: Noise in the pediatric
      unit exceeded recommended guidelines; however, decreasing the levels was possible
      and sustainable, which can improve the psychological and physiological wellbeing
      of hospitalized children.

PMID- 29381485
TI  - IRE1alpha RNase-dependent lipid homeostasis promotes survival in Myc-transformed
      cancers.
AB  - Myc activation is a primary oncogenic event in many human cancers; however, these
      transcription factors are difficult to inhibit pharmacologically, suggesting that
      Myc-dependent downstream effectors may be more tractable therapeutic targets.
      Here, we show that Myc overexpression induces endoplasmic reticulum (ER) stress
      and engages the inositol-requiring enzyme 1alpha (IRE1alpha)/X-box binding
      protein 1 (XBP1) pathway through multiple molecular mechanisms in a variety of c
      Myc- and N-Myc-dependent cancers. In particular, Myc-overexpressing cells require
      IRE1alpha/XBP1 signaling for sustained growth and survival in vitro and in vivo,
      dependent on elevated stearoyl-CoA-desaturase 1 (SCD1) activity. Pharmacological
      and genetic XBP1 inhibition induces Myc-dependent apoptosis, which is alleviated
      by exogenous unsaturated fatty acids. Of note, SCD1 inhibition phenocopies
      IRE1alpha RNase activity suppression in vivo. Furthermore, IRE1alpha inhibition
      enhances the cytotoxic effects of standard chemotherapy drugs used to treat c-Myc
      overexpressing Burkitt's lymphoma, suggesting that inhibiting the IRE1alpha/XBP1
      pathway is a useful general strategy for treatment of Myc-driven cancers.

PMID- 29381487
TI  - Mandibulofacial dysostosis Guion-Almeida type caused by novel EFTUD2 splice site
      variants in two Asian children.
AB  - Mandibulofacial dysostosis type Guion-Almeida (MFDGA) is a rare disease entity
      that results in congenital craniofacial anomalies that are caused by abnormal
      development of the first and second pharyngeal arches. MFDGA is characterized by
      malar and mandibular hypoplasia, microcephaly, developmental delay, dysplastic
      ears, and a distinctive facial appearance. Extracraniofacial malformations
      include esophageal atresia, congenital heart disease, and radial ray
      abnormalities. Heterozygous mutations in the elongation factor Tu GTP-binding
      domain containing 2 (EFTUD2) gene have been shown to result in MFDGA. To date,
      there have been a total of 108 individuals reported in the literature, of whom 95
      patients have a confirmed EFTUD2 mutation. The majority of individuals reported
      in the literature have been of White ethnic origin. Here, we report two
      individuals of Asian ancestry with MFDGA, each harboring a novel, pathogenic
      splice site variant in EFTUD2.

PMID- 29381488
TI  - Anatomic Relationship Between the Hook of the Hamate and the Distal Transverse
      Carpal Ligament: Implications for Ultrasound-Guided Carpal Tunnel Release.
AB  - OBJECTIVE: During ultrasound-guided carpal tunnel release, osseous landmarks may
      supplement direct visualization of the distal transverse carpal ligament (dTCL)
      to ensure a complete release. The purpose of this study was to determine the
      relationship between the apex of the hook of the hamate (aHH) and the dTCL within
      the transverse safe zone (TSZ) of the carpal tunnel. DESIGN: Twenty unembalmed
      cadaveric specimens were dissected to determine the aHH-dTCL distance and the aHH
      SPA distance (the distance between the aHH and the superficial palmar arch) at
      the ulnar and radial limits of the TSZ (the distance between the hook of the
      hamate or ulnar artery to the median nerve). RESULTS: The aHH-dTCL distance
      averaged 11-12 mm across the TSZ (maximum, 18.2 mm), whereas the aHH-SPA distance
      was significantly greater on the radial side of the TSZ compared with the ulnar
      side (22.6 +/- 3.6 mm vs. 14.0 +/- 4.0 mm). CONCLUSIONS: The dTCL lies
      approximately 11-12 mm distal to the aHH across the TSZ, with an upper limit of
      18.2 mm. Along with direct sonographic visualization of the dTCL, the aHH can be
      used with other osseous landmarks to estimate the position of the dTCL during
      ultrasound-guided carpal tunnel release.

PMID- 29381489
TI  - Abdominal prehospital ultrasound impacts treatment decisions in a Dutch
      Helicopter Emergency Medical Service.
AB  - OBJECTIVE: The aim of this study was to determine the impact of abdominal
      prehospital ultrasound (PHUS) on patient care in a Dutch physician-staffed
      Helicopter Emergency Medical Service (HEMS) and to determine its diagnostic
      performance. PATIENTS AND METHODS: We carried out a retrospective analysis of
      abdominal ultrasound (US) examinations performed by the HEMS of Nijmegen, the
      Netherlands, from January 2007 until December 2016. Data including patient
      demographics, type of incident, abdominal US findings, impact on treatment
      decisions, and the physicians' narrative report were retrieved from the HEMS
      database and analyzed. PHUS diagnostic performance was compared with computed
      tomography scan or laparotomy. RESULTS: Of 17 077 recorded scrambles and 8699
      patients treated, 1583 underwent 1631 abdominal US examinations. After
      eliminating missing data, 251 impacts on treatment in 194 out of 1539 PHUS
      examinations were identified (12.6%, 95% confidence interval: 10.9-14.3). This
      affected 188 out of 1495 (12.6%) patients. The four main categories of treatment
      decisions impacted by PHUS were information provided to the destination hospital
      (45.4%); mode of transportation (23.5%); choice of destination hospital (13.1%);
      and fluid management (11.6%). The sensitivity of prehospital abdominal US for
      hemoperitoneum was 31.3%, specificity was 96.7%, and accuracy was 82.1%.
      CONCLUSION: Abdominal PHUS in our setting impacts treatment decisions
      significantly. Therefore, it is a valuable tool in the Dutch HEMS setting and
      probably beyond.

PMID- 29381490
TI  - Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus
      bicalutamide on the androgen receptor pathway in prostate cancer cell lines.
AB  - Apalutamide (ARN-509) is an antiandrogen that binds selectively to androgen
      receptors (AR) and does not show antagonist-to-agonist switch like bicalutamide.
      We compared the activity of ARN versus bicalutamide on prostate cancer cell
      lines. The 22Rv1, PC3, and DU145 cell lines were used to study the effect of ARN
      and bicalutamide on the expression cytoplasmic/nuclear kinetics of AR, AR-V7
      variant, phosphorylated AR, as well as the levels of the AR downstream proteins
      prostate-specific antigen and TMPRSS2, under exposure to testosterone and/or
      hypoxia. The effects on autophagic flux (LC3A, p62, TFEB, LAMP2a, cathepsin D)
      and cell metabolism-related enzymes (hypoxia-inducible factor 1alpha/2alpha,
      BNIP3, carbonic anhydrase 9, LDHA, PDH, PDH-kinase) were also studied. The 22Rv1
      cell line responded to testosterone by increasing the nuclear entry of AR, AR-V7,
      and phosphorylated AR and by increasing the levels of prostate-specific antigen
      and TMPRSS2. This effect was strongly abrogated by ARN and to a clearly lower
      extent by bicalutamide at 10 MUmol/l, both in normoxia and in hypoxia. ARN had a
      stronger antiproliferative effect than bicalutamide, which was prominent in the
      22Rv1 hormone-responsive cell line, and completely repressed cell proliferation
      at a concentration of 100 MUmol/l. No effect of testosterone or of antiandrogens
      on autophagy flux, hypoxia-related proteins, or metabolism enzyme levels was
      noted. The PC3 and DU145 cell lines showed poor expression of the proteins and
      were not responsive to testosterone. On the basis of in-vitro studies, evidence
      has been reported that ARN is more potent than bicalutamide in blocking the AR
      pathway in normoxia and in hypoxia. This reflects a more robust, dose-dependent,
      repressive effect on cell proliferation.

PMID- 29381491
TI  - Investigation of an antitumor drug-delivery system based on anti-HER2 antibody
      conjugated BSA nanoparticles.
AB  - Conjugation of a monoclonal antibody with a nanoparticle often improves its
      specificity and drug loading in cancer therapy. In this study, we prepared a
      novel targeting nanodrug-delivery system using 2-methoxy-estradiol (2-ME) based
      on anti-human epidermal growth factor receptor 2 (HER2) antibody-modified BSA to
      improve the clinical application and antitumor effect of 2-ME. 2-ME-loaded
      albumin nanoparticles (2-ME-BSANPs) were prepared using a desolvation method and
      the anti-HER2 antibodies were conjugated to 2-ME-BSANPs (HER2-2-ME-BSANPs) using
      the coupling agent, succinimidyl 3-(2-pyridyldithio)propionate. HER2-2-ME-BSANPs
      were characterized using SDS-polyacrylamide gel electrophoresis, an agglutination
      test, and an immunofluorescence assay. We found that mouse anti-human anti-HER2
      monoclonal antibody was successfully conjugated to the 2-ME-BSANPs. Thereafter,
      the in-vitro and in-vivo toxicities were evaluated using two cancer cell lines,
      SK-BR-3 (HER2-overexpressing) and MCF-7 (HER2-underexpressing), using classic
      pharmacological methods and in-vivo imaging technology. We found that the HER2-2
      ME-BSANPs retained the immunospecificity of the anti-HER2 monoclonal antibody,
      rapidly localized to HER2 receptors, and could be used for targeted cancer
      therapy.

PMID- 29381492
TI  - Lung Function in Oil Spill Response Workers 1-3 Years After the Deepwater Horizon
      Disaster.
AB  - BACKGROUND: Little is known about the effects of inhalation exposures on lung
      function among workers involved in the mitigation of oil spills. Our objective
      was to determine the relationship between oil spill response work and lung
      function 1-3 years after the Deepwater Horizon (DWH) disaster. METHODS: We
      evaluated spirometry for 7,775 adults living in the Gulf states who either
      participated in DWH response efforts (workers) or received safety training but
      were not hired (nonworkers). At an enrollment interview, we collected detailed
      work histories including information on potential exposure to dispersants and
      burning oil/gas. We assessed forced expiratory volume in 1 second (FEV1; mL),
      forced vital capacity (FVC; mL), and the ratio (FEV1/FVC%) for differences by
      broad job classes and exposure to dispersants or burning oil/gas using
      multivariable linear and modified Poisson regression. RESULTS: We found no
      differences between workers and nonworkers. Among workers, we observed a small
      decrement in FEV1 (Beta, -71 mL; 95% confidence interval [CI], -127 to -14) in
      decontamination workers compared with support workers. Workers with high
      potential exposure to burning oil/gas had reduced lung function compared with
      unexposed workers: FEV1 (Beta, -183 mL; 95% CI, -316 to -49) and FEV1/FVC (Beta, 
      1.93%; 95% CI, -3.50 to -0.36), and an elevated risk of having a FEV1/FVC in the
      lowest tertile (prevalence ratio, 1.38; 95% CI, 0.99 to 1.92). CONCLUSIONS: While
      no differences in lung function were found between workers and nonworkers, lung
      function was reduced among decontamination workers and workers with high exposure
      to burning oil/gas compared with unexposed workers.

PMID- 29381493
TI  - Is the Association Between Obesity and Hip Osteoarthritis Surgery Explained by
      Familial Confounding?
AB  - BACKGROUND: Familial confounding is confounding due to genetics or environmental
      exposures shared by family members. We aimed to study whether familial
      confounding explains the association between body mass index (BMI) and severe hip
      osteoarthritis (OA). METHODS: We linked data from the Norwegian Arthroplasty
      Registry with the Norwegian Twin Registry on the National ID-number in 2014,
      generating a population-based prospective cohort study of same-sex twins born
      between 1915 and 1960 (53.4% females). BMI was calculated from self-reported
      height/weight. The outcome was incident hip arthroplasty due to OA (follow-up
      time, 1987-2014; 424 914 person-years). We performed sex-specific co-twin control
      analyses of dizygotic (N = 5,226) and monozygotic (MZ, N = 3,803) twin pairs
      using Cox regression models and explored reasons for any familial confounding
      using bivariate twin models. RESULTS: The mean (SD) BMI was 22.6 (2.96), peak
      lifetime BMI 25.6 (2.61), and N = 614 had hip surgery due to OA. In cohort
      analyses, BMI was associated with hip OA for women and men (hazard ratio [HR] =
      1.09, 95% confidence intervals [CIs] = 1.06 to 1.11 and HR = 1.08, 95% CI = 1.04
      to 1.12, respectively). When adjusting for familial confounding within MZ twins,
      the association got stronger for women (HR = 1.19; 95% CI = 1.05 to 1.36) but
      weaker for men (HR = 0.93; 95% CI = 0.75 to 1.16). There was no genetic overlap
      between BMI and hip OA, yet the familial confounding in men provides suggestive
      evidence that the association could be explained by shared environmental factors.
      CONCLUSION: The association between BMI and hip OA may be explained by familial
      confounding for men. For women, there was no evidence for familial confounding,
      consistent with a causal association. See video abstract at,
      http://links.lww.com/EDE/B336.

PMID- 29381494
TI  - Menstrual Cycle in Women Who Co-use Marijuana and Tobacco.
AB  - OBJECTIVE: Marijuana is the most commonly used illicit drug in the United States
      and co-use with tobacco is increasing. Preliminary studies have indicated that
      marijuana may suppress luteinizing hormone (LH) or shorten the luteal phase.
      Although the literature is mixed, these sex hormones may play a role in smoking
      cessation outcomes. This secondary subgroup analysis aims to explore the
      menstrual cycle of females who co-use marijuana and tobacco compared with females
      who only use tobacco in a sample of tobacco treatment-seeking individuals.
      METHODS: Female participants, aged 18 to 50 years, who self-reported regular
      menstrual cycles and co-use of marijuana and tobacco were matched 1:3 by age to
      participants who only use tobacco. Length of the follicular and luteal phases was
      determined using First Response Urine LH tests. Wilcoxon 2-sample t tests were
      used to determine differences in phase lengths between groups. RESULTS: Thirteen
      women who co-use marijuana and tobacco, and 39 women who only use tobacco were
      included in this analysis. Overall, participants were 37.3 +/- 8.0 (SD) years of
      age, mostly Caucasian (67%), and smoked 12.6 +/- 5.2 (SD) cigarettes per day. The
      luteal phase length among participants who co-use marijuana and tobacco (11.4
      days +/- 2.2 [SD]) was significantly shorter than among participants who only use
      tobacco (16.8 days +/- 11.3 [SD]; P = 0.002). No differences were found in
      follicular phase length or menstrual cycle length. CONCLUSIONS: These data
      suggest that females who co-use marijuana and tobacco may have a shortened luteal
      phase in comparison with females who only use tobacco. Further studies are needed
      to better understand how marijuana use may impact the menstrual cycle and affect
      smoking outcomes.

PMID- 29381495
TI  - The PEARLS Healthcare Debriefing Tool.

PMID- 29381497
TI  - Comparison of Vaginal Axis in Women who Have Undergone Hysterectomy Versus Women
      With an Intact Uterus.
AB  - OBJECTIVES: To compare vaginal axis and posterior cul-de-sac measurements in
      women who have undergone hysterectomy and women with an intact uterus. METHODS:
      This was a retrospective cohort study comparing magnetic resonance imaging
      findings in women who had undergone hysterectomy with women with an intact
      uterus. The primary outcome was change in the upper, middle, and lower vaginal
      axes relative to the pelvic inclination correction system line. Secondary
      outcomes included angles between the upper-middle and middle-lower vagina, depth
      of the posterior cul-de-sac, and total vaginal length. RESULTS: In the
      hysterectomy group, the middle vaginal axis was significantly more anterior as
      compared with the intact uterus group (61.3 degrees +/- 12.7 vs 49.4 degrees +/-
      23.6, P = 0.01). The upper-middle and the middle-lower vaginal angles were
      significantly more obtuse in the hysterectomy group than the intact uterus group
      (112.3 degrees +/- 28.7 vs 69.3 degrees +/- 56.6, P = 0.01 and 145.4 degrees +/-
      13.2 vs 130.9 degrees +/- 29.7, P = 0.02, respectively). The mean depth of the
      posterior cul-de-sac and the total vaginal length were significantly shorter in
      the hysterectomy group than the intact uterus group (5.5 mm +/- 7.6 vs 21.8 mm +/
      11.9, P < 0.0001 and 78.7 mm +/- 3.9 vs 100 mm +/- 15.9, P < 0.001,
      respectively). CONCLUSIONS: The vaginal anatomy of women who have undergone
      hysterectomy differs significantly from that of women with an intact uterus.

PMID- 29381498
TI  - Effectiveness of oral hydration in preventing contrast-induced acute kidney
      injury in patients undergoing coronary angiography or intervention: a pairwise
      and network meta-analysis.
AB  - BACKGROUND: The effectiveness of oral hydration in preventing contrast-induced
      acute kidney injury (CI-AKI) in patients undergoing coronary angiography or
      intervention has not been well established. This study aims to evaluate the
      efficacy of oral hydration compared with intravenous hydration and other
      frequently used hydration strategies. METHODS: PubMed, Embase, Web of Science,
      and the Cochrane central register of controlled trials were searched from
      inception to 8 October 2017. To be eligible for analysis, studies had to evaluate
      the relative efficacy of different prophylactic hydration strategies. We selected
      and assessed the studies that fulfilled the inclusion criteria and carried out a
      pairwise and network meta-analysis using RevMan5.2 and Aggregate Data Drug
      Information System 1.16.8 software. RESULTS: A total of four studies (538
      participants) were included in our pairwise meta-analysis and 1754 participants
      from eight studies with four frequently used hydration strategies were included
      in a network meta-analysis. Pairwise meta-analysis indicated that oral hydration
      was as effective as intravenous hydration for the prevention of CI-AKI (5.88 vs.
      8.43%; odds ratio: 0.73; 95% confidence interval: 0.36-1.47; P>0.05), with no
      significant heterogeneity between studies. Network meta-analysis showed that
      there was no significant difference in the prevention of CI-AKI. However, the
      rank probability plot suggested that oral plus intravenous hydration had a higher
      probability (51%) of being the best strategy, followed by diuretic plus
      intravenous hydration (39%) and oral hydration alone (10%). Intravenous hydration
      alone was the strategy with the highest probability (70%) of being the worst
      hydration strategy. CONCLUSION: Our study shows that oral hydration is not
      inferior to intravenous hydration for the prevention of CI-AKI in patients with
      normal or mild-to-moderate renal dysfunction undergoing coronary angiography or
      intervention.

PMID- 29381499
TI  - The CARE Act: Identifying and Supporting Family Caregivers From Hospitals to
      Home.

PMID- 29381500
TI  - Pregnancy-Related Coronary Artery Dissection: Recognition of a Life Threatening
      Process.
AB  - Pregnancy-related spontaneous coronary artery dissection (P-SCAD) is a rare but
      life-threatening condition of the peripartum and postpartum mother. The gold
      standard of diagnosing P-SCAD is a left cardiac catheterization; however, this
      diagnostic tool may not be used early because myocardial infarction is not
      typically a top differential diagnosis for women and especially young pregnant
      women presenting with acute chest pain. Providers and registered nurses,
      particularly those in the prehospital setting, the emergency department, and
      labor and delivery units, should be aware of signs, symptoms, potential risk
      factors, and diagnostic results that could indicate P-SCAD and initiate early and
      appropriate treatment to improve maternal outcomes.

PMID- 29381501
TI  - Using Critical Care Simulations to Prepare Nursing Students for Capstone Clinical
      Experiences.
AB  - The purpose of this innovative learning strategy was to decrease students' fear
      and anxiety within the critical care environment before the initiation of a
      critical care capstone clinical experience by enhancing their familiarity of the
      critical care environment through deliberate practice and experiential learning.
      This will in turn increase student knowledge and competence in the critical care
      setting.Critical care units are often used during a capstone clinical experience
      to enhance critical thinking and clinical reasoning. Student preparation for
      these rotations, however, is varied and often inadequate. The resulting fear and
      anxiety impair learning and also contribute to an unsafe environment for this at
      risk population.Before the capstone experience, students participated in 3
      simulation experiences, each addressing a core concept of critical care nursing.
      Faculty engaged students during the simulations, while modeling the confidence
      and critical thinking of a critical care nurse.After both the critical care
      simulation and the capstone rotation, students stated that the simulation allowed
      them the time in a safe environment to critically think through the steps to care
      for critical patients before the capstone rotation. The experience provided them
      with increased confidence necessary to discharge the responsibilities of a
      critical care nurse-attention to critical thinking and reasoning.Mindfully
      constructed simulations with clear objectives help to inoculate the student
      against fears associated with high-risk patients. This decrease in fear and
      anxiety before a hands-on clinical experience may improve patient safety. More
      confident students are also better able to engage in both experiential and
      deliberate learning, resulting in a more enhanced and meaningful clinical
      experience.

PMID- 29381502
TI  - The Effect of Cardiac Education on Knowledge and Self-care Behaviors Among
      Patients With Heart Failure.
AB  - BACKGROUND: No studies have been conducted in Jordan to examine the effect of
      cardiac education on knowledge and self-care behaviors among patients with heart
      failure in Jordan. PURPOSE: The purpose of this study was to examine the effect
      of a cardiac educational program on knowledge and self-care behaviors among
      patients with heart failure. METHOD: A quasi-experimental pretest/posttest design
      was used. A convenient sample of 127 patients with heart failure was recruited.
      The participants were randomly assigned to either experimental (n = 55) or
      control (n = 65) group. Knowledge and self-care were measured at 1 and 3 months
      after the program application. RESULTS: Results indicated that the change of
      knowledge mean score was statistically significant, P <= .001, between the
      pretest and both the first and second posttests for the experimental group
      compared with the control group. The change of maintenance self-care mean was
      statistically significant, P <= .001, between the pretest and both the first and
      second posttests for the experimental group compared with the control group.
      Moreover, the change in the management self-care mean was statistically
      significant, P <= .001, between the pretest and both the first and second
      posttests for the experimental group compared with the control group. Finally,
      the change of confidence self-care mean was statistically significant, P <= .001,
      between the pretest and both the first and second posttests for the experimental
      group compared with the control group. CONCLUSION: Applying cardiac education
      program helps improve knowledge and self-care among patients with heart failure.
      Such educational programs should be adopted in clinical settings to enhance
      knowledge and self-care behaviors.

PMID- 29381504
TI  - Reducing Anxiety and Improving Engagement in Health Care Providers Through an
      Auricular Acupuncture Intervention.
AB  - BACKGROUND: Stress and anxiety are experienced by health care providers as a
      consequence of caregiving and may result in physical, emotional, and
      psychological outcomes that negatively impact work engagement. AIM: The purpose
      of this study was to determine whether auricular acupuncture can reduce provider
      anxiety and improve work engagement. METHODS: Study participants received 5
      auricular acupuncture sessions within a 16-week period utilizing the National
      Acupuncture Detoxification Association protocol for treating emotional trauma.
      Each participant completed the State-Trait Anxiety Inventory and the Utrecht Work
      Engagement Scale (UWES-9) prior to their first session and again after their
      fifth treatment. RESULTS: Significant reductions were found in state and trait
      anxiety (State-Trait Anxiety Inventory), as well as significant increases in the
      overall scores on the UWES as compared with baseline. Only the dedication
      subcategory of the UWES showed significant improvement. CONCLUSIONS: Engagement
      has been linked to increased productivity and well-being and improved patient and
      organizational outcomes. Providing effective strategies such as auricular
      acupuncture to support health care providers in reducing anxiety in the workplace
      may improve engagement.

PMID- 29381505
TI  - Evaluating Sleep in a Surgical Trauma Burn Intensive Care Unit: An Elusive
      Dilemma.
AB  - BACKGROUND: Evidence points to the adverse effects of sleep deprivation on a
      person's health. Despite decades of attention to the issue, patients,
      particularly those in the intensive care unit (ICU), continue to suffer.
      OBJECTIVE: The purpose of this pilot study was to examine patients' perceptions
      of their sleep experience in the surgical trauma burn ICU and identify
      contributing factors. METHODOLOGY: Patients were administered the 6-question
      Richards-Campbell Sleep Questionnaire (RCSQ) consisting of a 0- to 100-mm scale,
      with a low score indicating poor sleep quality. They were also asked an
      additional open-ended question. RESULTS: Sixty patients participated. Data
      revealed a low overall RCSQ score of 43.6 of 100. Of the 5 validated questions on
      the RCSQ, the question with the lowest mean (35.6) targeted depth of sleep. The
      question pertaining to falling asleep immediately scored the highest at 52.2. The
      open-ended question revealed that 37% reported "interruptions" as the reason for
      not sleeping. Pain was also cited as a factor by 30%, with 11.7% citing
      discomfort from the bed as an irritant. An additional 21.6% reported noise as the
      central reason, with "pumps/monitor" noise as the most frequent culprit at 62%.
      DISCUSSION: The pilot study results demonstrate that most participants perceived
      their sleep as poor in quality. These results direct targeted interventions that
      can be incorporated to reduce sleep deprivation in ICUs.

PMID- 29381506
TI  - Building Connections With Patients and Families in the Intensive Care Unit: A
      Canadian Top-Performer Success Story.
AB  - Consumers are increasingly becoming the voice and impetus for hospital
      organizational change in the United States. This is in part due to their
      increased stake in cost sharing with hospitals, health systems, and the
      ambulatory setting and revisions to health plans with higher deductibles and
      copays. With customers wanting services better, faster, and more economical than
      in the past, organizations need to break the ceiling on improvement levels for
      exceeding expectations of patient experience. Of interest is the hospital
      critical care area, because of the heightened patient needs, support, and
      resources that are required in this acute setting. Bluewater Health, located in
      Sarnia, Ontario, Canada, is a top-industry performer on the patient experience
      access-to-care dimension. Much can be learned from the multiple practices it has
      used to create an environment that embraces patients and families to the fullest
      extent, ensuring the resources needed for optimizing care are received.

PMID- 29381507
TI  - Millennial Loyalty-Are You Capturing a Highly Relevant Generational Cohort?

PMID- 29381509
TI  - Aspirin suppresses neuronal apoptosis, reduces tissue inflammation, and restrains
      astrocyte activation by activating the Nrf2/HO-1 signaling pathway.
AB  - The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element
      signaling pathway plays a substantial role in preventing oxidative stress-related
      diseases. Aspirin has been shown to exert several pharmacological effects by
      inducing the expression of the heme oxygenase-1 (HO-1) protein. However, the
      effects of aspirin on spinal cord injury (SCI) have rarely been studied.
      Therefore, we sought to investigate the neuroprotective effects of aspirin after
      SCI. We employed a spinal cord contusion model in Sprague-Dawley rats, and
      aspirin was administered intraperitoneally for 7 days. Nissl staining showed that
      the aspirin treatment significantly reduced the loss of motor neurons after SCI
      compared with vehicle-treated animals. The expression of Nrf2, quinine
      oxidoreductase 1, and HO-1 proteins was increased in aspirin-treated animals
      after SCI compared with the vehicle group. In addition, aspirin simultaneously
      decreased the expression of inflammation-related proteins, such as tumor necrosis
      factor-alpha and interleukin-6 after SCI. Moreover, the ratio of apoptotic
      neurons in the anterior horn and the levels of the apoptosis-related proteins
      caspase-3, cleaved caspase-3, and Bax were significantly decreased in the aspirin
      group compared with the vehicle group. Immunofluorescence staining was used to
      detect the colocalization of NeuN and HO-1, and the results showed that aspirin
      significantly increased expression of the HO-1 protein in neurons. In addition,
      western blots and immunofluorescence staining showed aspirin restrained astrocyte
      activation. In conclusion, aspirin induces neuroprotective effects by inhibiting
      astrocyte activation and apoptosis after SCI through the activation of the
      Nrf2/HO-1 signaling pathway.

PMID- 29381510
TI  - Adding Dopamine to Proxymetacaine or Oxybuprocaine Solutions Potentiates and
      Prolongs the Cutaneous Antinociception in Rats.
AB  - BACKGROUND: We evaluated the interaction of dopamine-proxymetacaine and dopamine-
      oxybuprocaine antinociception using isobolograms. METHODS: This experiment uses
      subcutaneous drug (proxymetacaine, oxybuprocaine, and dopamine) injections under
      the skin of the rat's back, thus simulating infiltration blocks. The dose-related
      antinociceptive curves of proxymetacaine and oxybuprocaine alone and in
      combination with dopamine were constructed, and then the antinociceptive
      interactions between the local anesthetic and dopamine were analyzed using
      isobolograms. RESULTS: Subcutaneous proxymetacaine, oxybuprocaine, and dopamine
      produced a sensory block to local skin pinpricks in a dose-dependent fashion. The
      rank order of potency was proxymetacaine (0.57 [0.52-0.63] MUmol/kg) >
      oxybuprocaine (1.05 [0.96-1.15] MUmol/kg) > dopamine (165 [154-177] MUmol/kg; P <
      .01 for each comparison) based on the 50% effective dose values. On the
      equianesthetic basis (25% effective dose, 50% effective dose, and 75% effective
      dose), the nociceptive block duration of proxymetacaine or oxybuprocaine was
      shorter than that of dopamine (P < .01). Oxybuprocaine or proxymetacaine
      coinjected with dopamine elicited a synergistic antinociceptive effect and
      extended the duration of action. CONCLUSIONS: Oxybuprocaine and proxymetacaine
      had a higher potency and provoked a shorter duration of sensory block compared
      with dopamine. The use of dopamine increased the quality and duration of skin
      antinociception caused by oxybuprocaine and proxymetacaine.

PMID- 29381511
TI  - The Evolving Dilemma of Factor XI in Pregnancy: Suggestions for Management.
AB  - A case of a patient with severe factor XI (FXI) deficiency who presented for her
      seventh labor and delivery is presented. The nature of FXI deficiency, its
      prevalence, and issues related to genetic screening are discussed. Published
      literature on the topic is reviewed, including criteria that were developed to
      assess bleeding, laboratory tools used to estimate bleeding risk, and available
      treatments. Within the context of this challenging clinical dilemma, specific
      recommendations are provided for the antepartum, intrapartum, and postpartum
      stages of pregnancy. These include recommendations that take into account both
      FXI levels and history of any abnormal bleeding. While there are effective
      treatments available, it is important to consider that institutional
      multidisciplinary protocols are needed to manage this complex disorder. More work
      is needed to define the best management protocols.

PMID- 29381512
TI  - Sex Difference of Angiotensin IV-, LVV-Hemorphin 7-, and Oxytocin-Induced
      Antiallodynia at the Spinal Level in Mice With Neuropathic Pain.
AB  - BACKGROUND: We demonstrated previously that angiotensin IV (Ang IV) and LVV
      hemorphin 7 (LVV-H7) act through the blockade of insulin-regulated aminopeptidase
      to decrease oxytocin degradation, thereby causing antihyperalgesia at the spinal
      level in rats. We determined that intrathecal oxytocin can induce significant
      antihyperalgesia in male rats with inflammation but not in female rats. Thus, we
      speculate that Ang IV, LVV-H7, and oxytocin can induce antiallodynia, which could
      be of great therapeutic potential. Because the antihyperalgesia by using these
      peptides was with sex difference, their possible antiallodynia was examined in
      male and female mice for comparison. We investigated whether Ang IV, LVV-H7, and
      oxytocin produce antiallodynia at the spinal level in mice and whether this
      antiallodynia differs between the sexes. METHODS: Partial sciatic nerve ligation
      surgery was performed on adult male and female C57BL/6 mice from the same litter
      (25-30 g). The effects of intrathecal injections of Ang IV (25.8 nmol), LVV-H7
      (27.2 nmol), and oxytocin (0.125 or 1.25 nmol) were assessed through the von Frey
      test 3 days after partial sciatic nerve ligation. RESULTS: Intrathecal injection
      of Ang IV, LVV-H7, and oxytocin all produced a potent antiallodynia in male mice.
      However, these antiallodynia effects were either extremely weak or absent in
      female mice at the same dose. CONCLUSIONS: Intrathecal Ang IV, LVV-H7, and
      oxytocin can all cause significant antiallodynia in male mice. The Ang IV-, LVV
      H7-, and oxytocin-induced antiallodynia effects differed between the sexes at the
      spinal level in mice.

PMID- 29381513
TI  - A Systematic Review of Outcomes Associated With Withholding or Continuing
      Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Before
      Noncardiac Surgery.
AB  - BACKGROUND: The global rate of major noncardiac surgical procedures is increasing
      annually, and of those patients presenting for surgery, increasing numbers are
      taking either an angiotensin-converting enzyme inhibitor (ACE-I) or an
      angiotensin receptor blocker (ARB). The current recommendations of whether to
      continue or withhold ACE-I and ARB in the perioperative period are conflicting.
      Previous meta-analyses have linked preoperative ACE-I/ARB therapy to the
      increased incidence of postinduction hypotension; however, they have failed to
      correlate this with adverse patient outcomes. The aim of this meta-analysis was
      to determine whether continuation or withholding ACE-I or ARB therapy in the
      perioperative period is associated with mortality and major morbidity. METHODS:
      This meta-analysis was prospectively registered on PROSPERO (CRD42017055291). A
      comprehensive search of MEDLINE (PubMed), CINAHL (EBSCO host), ProQuest, Cochrane
      database, Scopus, and Web of Science was conducted on December 6, 2016. We
      included adult patients >18 years of age on chronic ACE-I or ARB therapy who
      underwent noncardiac surgery in which ACE-I or ARB was either withheld or
      continued on the morning of surgery. Primary outcomes included all-cause
      mortality and major cardiac events (MACE). Secondary outcomes included the risk
      of congestive heart failure, acute kidney injury, stroke,
      intraoperative/postoperative hypotension, and the length of hospital stay.
      RESULTS: After abstract review, the full text of 25 studies was retrieved, of
      which 9 fulfilled the inclusion criteria: 5 were randomized control trials, and 4
      were cohort studies. These studies included a total of 6022 patients on chronic
      ACE-I/ARB therapy before noncardiac surgery. A total of 1816 patients withheld
      treatment the morning of surgery and 4206 continued their ACE-I/ARB. Preoperative
      demographics were similar between the 2 groups. Withholding ACE-I/ARB therapy was
      not associated with a difference in mortality (odds ratio [OR], 0.97; 95%
      confidence interval [CI], 0.62-1.52; I = 0%) or MACE (OR, 1.12; 95% CI, 0.82
      1.52; I = 0%). However, withholding therapy was associated with significantly
      less intraoperative hypotension (OR, 0.63; 95% CI, 0.47-0.85; I = 71%). No effect
      estimate could be pooled concerning length of hospital stay and congestive heart
      failure. CONCLUSIONS: This meta-analysis did not demonstrate an association
      between perioperative administration of ACE-I/ARB and mortality or MACE. It did,
      however, confirm the current observation that perioperative continuation of ACE
      I/ARBs is associated with an increased incidence of intraoperative hypotension. A
      large randomized control trial is necessary to determine the appropriate
      perioperative management of ACE-I and ARBs.

PMID- 29381514
TI  - Activation of Melatonin Receptors by Ramelteon Induces Cardioprotection by
      Postconditioning in the Rat Heart.
AB  - Activation of melatonin receptors protects the heart against ischemia-reperfusion
      injury. Ramelteon, a clinically used drug for insomnia, acts via activation of
      melatonin receptors. We investigated whether ramelteon induces acute infarct size
      reduction by postconditioning. Male Wistar rats were randomized to 6 groups.
      Hearts were treated with melatonin and ramelteon at the beginning of reperfusion.
      The melatonin receptor inhibitor luzindole was administered with and without
      melatonin and ramelteon, respectively. Ramelteon reduced infarct size to the same
      extent as melatonin. Both effects were completely abolished by luzindole. The
      results show for the first time that ramelteon induces cardioprotection by
      postconditioning.

PMID- 29381515
TI  - In Response.

PMID- 29381516
TI  - Flupirtine: A Less-Explored, Neglected Nonopioid Analgesic.

PMID- 29381517
TI  - Misguided by INR in Liver Disease Patients? Implications for Clinicians Including
      Pain Proceduralists.

PMID- 29381519
TI  - Summative Objective Structured Clinical Examination Assessment at the End of
      Anesthesia Residency for Perioperative Ultrasound.
AB  - While standardized examinations and data from simulators and phantom models can
      assess knowledge and manual skills for ultrasound, an Objective Structured
      Clinical Examination (OSCE) could assess workflow understanding. We recruited 8
      experts to develop an OSCE to assess workflow understanding in perioperative
      ultrasound. The experts used a binary grading system to score 19 graduating
      anesthesia residents at 6 stations. Overall average performance was 86.2%, and 3
      stations had an acceptable internal reliability (Kuder-Richardson formula 20
      coefficient >0.5). After refinement, this OSCE can be combined with standardized
      examinations and data from simulators and phantom models to assess proficiency in
      ultrasound.

PMID- 29381520
TI  - Midterm functional outcomes in operatively treated adolescent Lisfranc injuries.
AB  - : This study evaluates the midterm outcomes of Lisfranc injuries in adolescents
      operatively treated with Kirschner wire or screw fixation. Eight adolescent
      patients with Lisfranc injuries operatively treated in a single institution were
      included in this study. The mean duration of follow-up was 3.8 years. Analysis of
      radiographs with respect to the degree of initial displacement and final
      reduction was carried out in terms of the intermetatarsal distances. All cases
      were scored functionally using the American Orthopaedic Foot and Ankle Society
      Midfoot Scale. We concluded that most operatively treated cases of adolescent
      Lisfranc injuries will do well at the midterm follow-up, with a mean American
      Orthopaedic Foot and Ankle Society Midfoot score of 93.4. LEVEL OF EVIDENCE:
      Level 4 (Case series).

PMID- 29381521
TI  - Extended Ponseti method for failed tenotomy in idiopathic clubfeet: a pilot
      study.
AB  - We evaluated the outcome of a new protocol of an extended Ponseti method in the
      management of idiopathic club foot with residual equinus following failed
      Achilles tenotomy. We also compared the failed with a successful tenotomy group
      to analyze the parameters for failure. The Ponseti technique-treated idiopathic
      club foot patients with failed percutaneous Achilles tenotomy (failure to achieve
      <15 degrees  dorsiflexion) were treated by continued stretching casts, with a
      weekly change for a further 3 weeks. Final dorsiflexion more than 15 degrees  if
      achieved with the above protocol was recorded as a success. Twenty-six (16%)
      patients with failed Achilles tenotomy and residual equinus out of a total of 161
      patients with primary idiopathic club foot were tested with the protocol. Ten
      (38.5%) failed patients had bilateral foot involvement and 16 (61.5%) had
      unilateral foot involvement. A total of seven (26.9%) patients achieved the end
      point dorsiflexion of more than 15 degrees  in one further cast, 10 (38.5%) in
      two casts, and four (15.4%) in three casts, respectively. Overall success of the
      extended Ponseti protocol was achieved in 21/26 (80.8%) patients. The patient's
      age, precasting initial Pirani score, number of Ponseti casts, pretenotomy Pirani
      score, and pretenotomy ankle joint dorsiflexion were statistically different in
      the failed compared with the successful tenotomy group. The tested extended
      Ponseti protocol showed a success rate of 80.8% in salvaging failed tenotomy
      cases. The failed tenotomy group was relatively older at presentation, had high
      precasting and pretenotomy Pirani scores, received extra number of Ponseti casts,
      and less pretenotomy ankle joint dorsiflexion compared with successful feet.

PMID- 29381522
TI  - Violaceous Pink Axillary and Intertriginous Patches: Answer.

PMID- 29381523
TI  - Bilateral Symmetric Hyperpigmented Forehead Patches: Answer.

PMID- 29381524
TI  - Bilateral Symmetric Hyperpigmented Forehead Patches: Challenge.

PMID- 29381525
TI  - Bilateral and Symmetrical Linear Plaques on the Hands: Challenge.

PMID- 29381526
TI  - The Modified Otago Exercises Prevent Grip Strength Deterioration Among Older
      Fallers in the Malaysian Falls Assessment and Intervention Trial (MyFAIT).
AB  - BACKGROUND AND PURPOSE: Exercise-based interventions, such as the Otago Exercise
      Program (OEP), are effective in preventing falls in the older adult. Previous
      studies evaluating the OEP have determined falls, lower limb strength, or balance
      outcomes but with lack of assessment of hand grip strength. The objective of this
      study is to evaluate the effect of OEP on hand grip strength alongside mobility
      and balance outcomes. METHODS: This was a single-center, prospective, and single
      blind randomized controlled trial conducted at the University Malaya Medical
      Centre. Patients older than 65 years presenting to the hospital emergency
      department or geriatric clinic with 1 injurious fall or 2 falls in the past year
      and with impaired functional mobility were included in the study. The
      intervention group received a modified OEP intervention (n = 34) for 3 months,
      while the control group received conventional care (n = 33). All participants
      were assessed at baseline and 6 months. RESULTS: Twenty-four participants in both
      OEP and control groups completed the 6-month follow-up assessments. Within-group
      analyses revealed no difference in grip strength in the OEP group (P = 1.00,
      right hand; P = .55, left hand), with significant deterioration in grip strength
      in the control group (P = .01, right hand; P = .005, left hand). Change in grip
      strength over 6 months significantly favored the OEP group (P = .047, right hand;
      P = .004, left hand). Significant improvements were also observed in mobility and
      balance in the OEP group. CONCLUSIONS: In addition to benefits in mobility and
      balance, the OEP also prevents deterioration in upper limb strength. Additional
      benefits of exercise interventions for secondary prevention of falls in term of
      sarcopenia and frailty should also be evaluated in the future.

PMID- 29381528
TI  - The Current State of Surgical Ergonomics Education in U.S. Surgical Training: A
      Survey Study.
AB  - OBJECTIVE: The aim of this study was to characterize the current state of
      surgical ergonomics education in the United States. BACKGROUND: The burden of
      work-related musculoskeletal disorders (MSDs) in surgeons is high and no
      overarching strategy for redress exists. Twelve distinct specialties describe an
      unmet need for surgical ergonomics education (SEE). This study aimed to define
      the current state of SEE in U.S. surgical training programs. METHODS: We
      performed a descriptive analysis of a 20-item questionnaire of ACGME-certified
      program directors from 14 surgical and interventional medical specialties. Formal
      SEE was defined as any organized education module that reviewed the occupation
      specific burden of common work-related MSDs and described a framework for
      prevention via occupation-specific applied ergonomics. Program directors were
      queried regarding SEE provision, characteristics, and perceived trainee attitude
      toward the education. RESULTS: Questionnaires were received from 130 of 441
      (29.5%) program directors. Two (1.5%) provided formal SEE and 33 (25.4%) provided
      informal SEE, which consisted of unstructured intraoperative directives and
      isolated lectures. Two programs previously provided SEE but discontinued the
      effort due to lack of an evidence-based framework and instructors. Trainees
      appeared to think that learning surgical ergonomics skills was a worthwhile time
      investment in 100% and 76.7% of current formal and informal SEE, respectively.
      CONCLUSION: SEE is rarely provided in any capacity (25.4%), let alone in a
      consistent or evaluable fashion (1.5%). Impediments to sustainable SEE include
      lack of an evidence-based framework for education and instructors. An evidence
      based, reproducible, and accreditation council-compliant SEE module would be a
      valuable resource for the surgical and interventional medical communities.

PMID- 29381530
TI  - The safety we weave.

PMID- 29381531
TI  - Nurse leader mentorship.

PMID- 29381527
TI  - Community, Public Policy, and Recovery from Mental Illness: Emerging Research and
      Initiatives.
AB  - This commentary examines the roles that communities and public policies play in
      the definition and processes of recovery for adults with mental illness. Policy,
      clinical, and consumer definitions of recovery are reviewed, which highlight the
      importance of communities and policies for recovery. This commentary then
      presents a framework for the relationships between community-level factors,
      policies, and downstream mental health outcomes, focusing on macroeconomic,
      housing, and health care policies; adverse exposures such as crime victimization;
      and neighborhood characteristics such as social capital. Initiatives that address
      community contexts to improve mental health outcomes are currently under way.
      Common characteristics of such initiatives and select examples are discussed.
      This commentary concludes with a discussion of providers', consumers', and other
      stakeholders' roles in shaping policy reform and community change to facilitate
      recovery.

PMID- 29381532
TI  - A nurse educator's guide to cultural competence.

PMID- 29381533
TI  - The state of nurse leader wellness: Results of the Nursing Management Wellness
      Survey.

PMID- 29381534
TI  - Using systems thinking to envision quality and safety in healthcare.

PMID- 29381535
TI  - Our finalist: Venetia Green.
AB  - The following manuscript is the finalist 2017 Richard Hader Visionary Leader
      Award entry, submitted to Nursing Management in recognition of Venetia Green,
      MSM, BSN, RN, CMSRN, director of inpatient nursing services at Schneck Medical
      Center in Seymour, Ind.

PMID- 29381536
TI  - Nursing Management Congress2017 Recap.

PMID- 29381537
TI  - The PRO leader model.
AB  - A transformative approach to influence change.

PMID- 29381538
TI  - When staff members won't stop texting.

PMID- 29381539
TI  - Ablative Lasers: 24 Years of Medical Malpractice Cases in the United States.

PMID- 29381541
TI  - A Port-Wine Stain Treated With Pulsed Dye Laser: A Complication From Contaminated
      Makeup.

PMID- 29381542
TI  - Three-Staged Reconstruction of a Nasal Defect.

PMID- 29381540
TI  - Swept-Source Optical Coherence Tomography-Supervised Biopsy.
AB  - BACKGROUND: Currently, only skin biopsy can provide definitive histological
      confirmation for the diagnosis of skin diseases. To improve the diagnostic
      accuracy and to assist the dermatologist, various imaging techniques have been
      added to the examination of skin. Among all these techniques, the recent advances
      in optical coherence tomography (OCT) have made it possible to image the skin up
      to 2 millimeters in depth. OBJECTIVE: To testify the feasibility of OCT imaging
      in skin biopsy, the authors investigated the OCT imaging for real-time
      visualization of needle insertion and punch biopsy techniques in both a tissue
      phantom and biological tissue. MATERIALS AND METHODS: A swept-source OCT with
      1,305-nm central wavelength was used in this study. The euthanized mouse was used
      for real-time visualization of needle insertion. A gelatin phantom with India ink
      was used to demonstrate the punch biopsy using OCT. RESULTS: Optical coherence
      tomography can provide guidance for skin injections as well as real-time imaging
      to assist in the performance of punch biopsy. CONCLUSION: Optical coherence
      tomography holds potential not only as a diagnostic tool in dermatology. It can
      also allow for visualization for more accurate drug delivery, and noninvasively
      assess the response to treatment.

PMID- 29381543
TI  - First Safety and Performance Evaluation of T45K, a Self-Assembling Peptide
      Barrier Hemostatic Device, After Skin Lesion Excision.
AB  - BACKGROUND: The self-assembling peptide barrier T45K (SAPB-T45K) is an
      oligopeptide that rapidly forms a biocompatible hemostatic barrier when applied
      to wounds. OBJECTIVE: Evaluate safety and performance of SAPB-T45K in cutaneous
      surgery. MATERIALS AND METHODS: In this single-blind study, after sequential
      shave excision of 2 lesions, wounds were randomized (intrapatient) to SAPB-T45K
      or control treatment. Safety was assessed at treatment, Day 7, and Day 30.
      Performance was evaluated using time to hemostasis (TTH) and ASEPSIS wound
      scores, with a subgroup analysis for patients with or without antiplatelet
      therapy. RESULTS: Each of 46 patients (10 [22%] with antiplatelet therapy)
      received randomized SAPB-T45K or control treatment for 2 wounds. Safety
      assessments were similar, and ASEPSIS scores reflected normal healing in both
      wound groups. SAPB-T45K demonstrated significantly faster median TTH (24.5
      [range, 7-165] seconds) compared with control (44 [10-387] seconds), for a 41%
      median TTH reduction (18 [95% confidence interval, 7-35] seconds, p < .001). SAPB
      T45K provided an identical median TTH of 24 seconds, regardless of antiplatelet
      therapy. Control median TTH was 90 and 40 seconds for patients taking or not
      taking antiplatelet therapy, respectively. CONCLUSIONS: SAPB-T45K provided
      significantly faster median TTH versus control, especially with antiplatelet
      therapy, and safety profiles were similar.

PMID- 29381544
TI  - A Single Center, Prospective, Randomized, Sham-Controlled, Double-Blinded, Split
      Face Trial Using Microinjections of Transparent Hyaluronic Acid Gel for Cheek
      Rejuvenation.
AB  - BACKGROUND: "Skin boosting" with injections of hyaluronic acid has been
      demonstrated to improve aged skin. OBJECTIVE: The aim of this study was to
      determine the efficacy and safety of small-particle hyaluronic acid with
      lidocaine (SP-HAL) microaliquots for the correction of fine lines of the cheeks.
      MATERIALS AND METHODS: Twenty subjects with mild to moderate static mid to lower
      cheek rhytides were enrolled. The right or left cheek was randomized to receive 1
      mL of SP-HAL using a microdroplet technique, with the contralateral cheek treated
      with sham injection of sterile normal saline. The degree of cheek wrinkling and
      elastosis based on the Fitzpatrick-Goldman Wrinkle and Elastosis Scale was
      assessed at baseline and 7, 14, 30, 90, and 180 days after treatment. Subjects
      rated their satisfaction at days 90 and 180. RESULTS: Fourteen patients completed
      the study. There were no statistically significant improvements in wrinkling or
      elastosis of the SP-HAL-treated cheek or control cheek at any time point. In
      addition, there were no significant differences in wrinkling, elastosis, or
      patient satisfaction between the treatment cheek and control cheek. CONCLUSION:
      One treatment of intradermal microdroplet injections of SP-HAL to the mid to
      lower cheek failed to show superiority over normal saline in improving clinical
      signs of skin wrinkling and elastosis.

PMID- 29381545
TI  - Reliability of the Patient and Observer Scar Assessment Scale When Used With
      Postsurgical Scar Photographs.

PMID- 29381546
TI  - Reconstruction of a Full-Thickness Auricular Defect After Mohs Micrographic
      Surgery.

PMID- 29381547
TI  - A Large Surgical Defect of the Central Forehead.

PMID- 29381548
TI  - The Effects of Postoperative Intralesional Corticosteroids in the Prevention of
      Recurrent Earlobe Keloids: A Multispecialty Retrospective Review.
AB  - BACKGROUND: Effective treatment of keloids is challenging because the recurrence
      rate after surgical excision is high. Data on the best treatment practices are
      lacking. OBJECTIVE: To investigate the recurrence rate after surgical excision of
      earlobe keloids based on a postoperative intralesional corticosteroid injection
      protocol. MATERIALS AND METHODS: Retrospective chart review was performed from
      January 1, 2005, to March 31, 2016, of patients who had excision of ear keloids
      within the departments of dermatology, otorhinolaryngology, and plastic surgery.
      The number of postoperative injections was recorded, recurrence was reported by
      the patient, and the efficacy of an injection protocol was evaluated. RESULTS:
      There were 277 charts reviewed. Appropriate data were available for 184 patients.
      A statistically significant difference was found with recurrence associated with
      a lower number of injections (p < .001). Keloids were more likely to recur if
      they were not treated with a planned serial injection protocol (p < .001) or if
      they were treated outside the department of dermatology (p < .001). CONCLUSION:
      Intralesional corticosteroid injection after surgical excision of earlobe keloids
      statistically minimizes the risk of recurrence.

PMID- 29381549
TI  - Myxoid Cyst as a Probable Complication of Nail Surgery.

PMID- 29381550
TI  - Commentary on A Single Center, Prospective, Randomized, Sham-Controlled, Double
      Blinded, Split-Face Trial Using Microinjections of Transparent Hyaluronic Acid
      Gel for Cheek Rejuvenation.

PMID- 29381551
TI  - Reply: Vectra 3D Imaging for Quantitative Volumetric Analysis of the Upper Limb:
      A Feasibility Study for Tracking Outcomes of Lymphedema Treatment.

PMID- 29381552
TI  - Reply: The Value of Secondary Intention Healing in Eyelid Reconstruction:
      Response to Recent CME Article by Chang, Esmaeli, and Butler - Content Needs to
      be Evidence-Based.

PMID- 29381554
TI  - Vectra 3D Imaging for Suprapubic Lymphedema and Volume Change of the Lower
      Abdomen Associated with Lower Extremity Lymphedema.

PMID- 29381553
TI  - Sural Nerve Splitting in Reverse Sural Artery Perforator Flap: Anatomical Study
      in 40 Cadaver Legs.

PMID- 29381555
TI  - The Value of Secondary Intention Healing in Eyelid Reconstruction: Response to
      Recent CME Article by Chang, Esmaeli and Butler - Content Needs to be Evidence
      Based.

PMID- 29381556
TI  - Pill in the Airway of a Lung Transplant Recipient.

PMID- 29381559
TI  - High rates of incident diabetes and prediabetes are evident in men with treated
      HIV followed for 11 years.
AB  - OBJECTIVE: To determine the long-term incidence of glucose disorders in treated
      HIV infection, associations with traditional and HIV-specific risk factors.
      METHODS: Observational cohort of 104 men with treated HIV infection and without
      diabetes, aged 43 +/- 8 years at baseline, with (mean +/- SD) 11.8 +/- 3.5 years
      follow-up. Ascertainment of glucose status by fasting glucose or, in a subset (n
      = 33), a 75 g oral glucose tolerance test by 10-12 years follow-up. A subset
      underwent sequential body composition measures (n = 58) to determine changes in
      total body and central abdominal adiposity. RESULTS: The cumulative incidence of
      glucose disorders was 45.8% (prediabetes 32.3%, diabetes 12.5%), with an
      incidence rate of 34.5/1000 years of patient follow-up (PYFU) (prediabetes:
      24.3/1000 PYFU; diabetes: 10.2/1000 PYFU). Incident glucose disorders were
      independently associated with higher age (44.9 +/- 8.4 vs. 41.1 +/- 7.5 years, P
      = 0.027), baseline C-peptide (2.9 +/- 1.3 vs. 2.4 +/- 1.1 ng/ml, P = 0.019) and
      baseline 2-h glucose (135 +/- 41 vs. 95 +/- 25 mg/dl, P < 0.001). A prior AIDS
      defining illness was independently associated with higher follow-up fasting
      glucose (108 +/- 38 vs. 94 +/- 16 mg/dl, P = 0.007). Abdominal fat gain over 2-4
      years was associated with a 3.16-fold increased risk of incident glucose
      disorders (95% CI 1.30-7.68, P = 0.011). In a subgroup who underwent further oral
      glucose tolerance testing, 60% had a glucose disorder, the majority not detected
      by fasting glucose. CONCLUSION: Men with long-term treated HIV infection have
      high rates of incident glucose disorders associated with modest abdominal fat
      gain. Directed measures to prevent diabetes in this population are warranted.

PMID- 29381558
TI  - Care continuum entry interventions: seek and test strategies to engage persons
      most impacted by HIV within the United States.
AB  - : The current review re-conceptualizes seek and test strategies, particularly
      given the changing importance of HIV testing as care continuum entry for persons
      irrespective of their HIV status. Care continuum entry advances previous seek and
      test strategies for client engagement with two next-generation functions: use of
      testing to engage (or re-engage) HIV negative clients in preexposure prophylaxis
      (PrEP) care; and testing individuals who may already be known positives for care
      continuum re-entry. We review existing seek and test strategies for most impacted
      community members with a goal of optimizing care continuum entry as we move
      towards HIV transmission elimination. These strategies are context, sub-group,
      community and epidemic-specific. This review is timely, given the initiation of
      routine PrEP care, which shifts and broadens our conceptualization of care
      continuum entry triggered by the HIV testing event. In addition, as the epidemic
      becomes more concentrated, focusing on re-engagement of HIV-infected persons
      becomes increasingly important given that transmission events involve both those
      acutely and newly infected as well as the large numbers who may not be virally
      suppressed. We start with examination of routine testing in healthcare settings,
      emphasizing its potential role in re-engagement for persons out of care.
      Subsequently, we describe risk-based testing to identify key populations. We then
      review network-based approaches and their impact on the epidemic. We close with
      future directions for individual and combination care continuum entry strategies
      most relevant to elimination of HIV transmission in the United States.

PMID- 29381560
TI  - Omega-3 decreases IL-6 levels in HIV and human herpesvirus-8 coinfected patients
      in Uganda.
AB  - OBJECTIVE: Kaposi sarcoma is a HIV-associated malignancy caused by human
      herpesvirus-8 (HHV-8) that occurs at highest incidence in sub-Saharan Africa.
      Kaposi sarcoma patients often present with inflammatory symptoms associated with
      higher mortality. DESIGN: We conducted a double-blind, randomized, placebo
      controlled study in Uganda to test whether omega-3 supplementation could reduce
      inflammation in HIV and HHV-8 coinfected adults. Patients with acute illness,
      AIDS, or advanced Kaposi sarcoma were ineligible, as were pregnant women.
      Participant IDs were pre-randomized, blocked by Kaposi sarcoma status, to either
      the omega-3 or placebo arm. METHODS: Omega-3 participants received a 3-g pill
      dose daily for 12 weeks (1.8-g eicosapentaenoic acid, 1.2-mg docosapentaenoic
      acid); placebo participants received 44.8 mg of high oleic safflower oil that
      appeared indistinguishable from the active supplement. Intervention effects were
      evaluated as the baseline-adjusted mean difference after 12 weeks between omega-3
      and placebo participants in concentrations of fatty acids, inflammatory
      cytokines, and immune cells. RESULTS: The final study population included 56
      Kaposi sarcoma patients and 11 Kaposi sarcoma-negative, HIV and HHV-8-positive
      participants randomized to receive either omega-3 (N = 33) or placebo (N = 34).
      Inflammatory cytokine IL-6 concentrations decreased in omega-3 participants (
      0.78 pg/ml) but increased in placebo participants (+3.2 pg/ml; P = 0.04). We
      observed a trend toward decreased IL-6 after omega-3 supplementation specific to
      Kaposi sarcoma patients (P = 0.08). CD8 T-cell counts tended to increase in the
      omega-3 arm Kaposi sarcoma patients (+60 cells/MUl), in contrast to decreases (
      47 cells/MUl) among placebo (P = 0.11). CONCLUSION: Omega-3 supplementation
      decreased IL-6 concentrations among HIV and HHV-8 coinfected Ugandans, which may
      have clinical benefit for Kaposi sarcoma patients.

PMID- 29381561
TI  - Acute hepatitis A breakthrough in MSM in Paris area: implementation of targeted
      hepatitis A virus vaccine in a context of vaccine shortage.

PMID- 29381562
TI  - Dolutegravir and metformin: a clinically relevant or just a pharmacokinetic
      interaction?

PMID- 29381563
TI  - Cytomegalovirus encephalitis in the post-HAART era: is there a gold standard for
      treatment?

PMID- 29381564
TI  - Neuropsychological performance in African children with HIV enrolled in a
      multisite antiretroviral clinical trial: Erratum.

PMID- 29381565
TI  - In Reply: Reproducibility of Central Corneal Thickness Measurements in Healthy
      and Glaucomatous Eyes.

PMID- 29381566
TI  - Urinary Biomarkers to Predict Neonatal Acute Kidney Injury: A Review of the
      Science.
AB  - Acute kidney injury (AKI) occurs in approximately 30% of all infants hospitalized
      in the neonatal intensive care unit. About 40% of very low-birth-weight infants
      develop AKI, with an estimated mortality rate of 50% to 80%. Very low-birth
      weight survivors have twice the risk of developing chronic renal disease later in
      life compared with their term counterparts. Current diagnostic modalities for AKI
      include serum creatinine and urine output; however, recent studies suggest that
      these measures are imprecise, as they may not change until 25% to 50% of renal
      function is lost. Urinary biomarkers may more accurately identify infants at risk
      for early AKI development. The purpose of this review is to discuss current
      research findings related to neonatal AKI risk factors, provide an overview of
      short- and long-term outcomes, describe innovative diagnostic approaches, and
      identify future research direction needed to improve prediction and intervention
      strategies associated with renal impairment.

PMID- 29381567
TI  - How Does the United States Rank According to the World Breastfeeding Trends
      Initiative?
AB  - The World Breastfeeding Trends Initiative is an assessment process designed to
      facilitate an ongoing national appraisal of progress toward the goals of the
      United Nations Children's Fund (UNICEF)/World Health Organization (WHO) Global
      Strategy for Infant and Young Child Feeding. More than 80 countries have
      completed this national assessment, including the United States of America. This
      article describes the process undertaken by the US World Breastfeeding Trends
      Initiative team, the findings of the expert panel related to infant and young
      child feeding policies, programs, and practices and the ranking of the United
      States compared with the 83 other participating nations. Identified strengths of
      the United States include data collection and monitoring, especially by the
      Centers for Disease Control and Prevention, the US Baby-Friendly Hospital
      Initiative, and the United States Breastfeeding Committee. The absence of a
      national infant feeding policy, insufficient maternity protection, and lack of
      preparation for infant and young children feeding in emergencies are key targets
      identified by the assessment requiring concerted national effort.

PMID- 29381568
TI  - The Lateral Femoral Cutaneous Nerve: Description of the Sensory Territory and a
      Novel Ultrasound-Guided Nerve Block Technique.
AB  - BACKGROUND AND OBJECTIVES: Nerve blockade of the lateral femoral cutaneous (LFC)
      nerve provides some analgesia after hip surgery. However, knowledge is lacking
      about the extent of the cutaneous area anesthetized by established LFC nerve
      block techniques, as well as the success rate of anesthetic coverage of various
      surgical incisions. Nerve block techniques that rely on ultrasonographic
      identification of the LFC nerve distal to the inguinal ligament can be
      technically challenging. Furthermore, the branching of the LFC nerve is variable,
      and it is unknown if proximal LFC nerve branches are anesthetized using the
      current techniques. The primary aim of this study was to investigate a novel
      ultrasound-guided LFC nerve block technique based on injection into the fat
      filled flat tunnel (FFFT), which is a duplicature of the fascia lata between the
      sartorius and the tensor fasciae latae muscle, in order to assess the success
      rate of anesthetizing the proximal LFC nerve branches and covering of the
      different surgical incisions used for hip surgery. METHODS: First, a cadaveric
      study was conducted in order to identify an FFFT injection technique that would
      provide adequate injectate spread to the proximal LFC nerve branches. Second, a
      clinical study was conducted in a group of 20 healthy volunteers over 2
      consecutive days. On trial day 1, successful complete anesthesia of the LFC nerve
      was defined by performing a suprainguinal fascia iliaca block bilaterally in each
      subject. On trial day 2, a triple-blind randomized controlled trial compared the
      effect of the novel ultrasound-guided LFC nerve block technique for bupivacaine
      versus placebo. The primary end point was the success rate of anesthesia of the
      proximal cutaneous area innervated by the LFC nerve for the FFFT injection with
      bupivacaine versus placebo. RESULTS: Adequate spread of injectate to the proximal
      LFC nerve branches in cadavers was obtained by injecting 10 mL with dynamic
      needle-tip tracking in the FFFT. Application of this technique in the randomized
      controlled trial provided anesthesia of the lateral thigh with a success rate of
      95% (95% confidence interval, 73.9%-99.8%) for the active side and 0% for placebo
      (P < 0.001). The proximal branches were anesthetized with a success rate of 68%
      (95% confidence interval, 43.4%-87.4%) on the active side. The proximal extent of
      the anesthetized cutaneous area was on average 7.9 cm distal to the greater
      trochanter. CONCLUSIONS: This novel LFC nerve block technique is easy and quick
      and reliably produces anesthesia of the lateral thigh. The greater trochanter is
      rarely included in the area of anesthesia, which reduces the coverage of each
      specific surgical incision. The success rate of 68% in anesthetizing the proximal
      nerve branches must be further evaluated by future research.

PMID- 29381569
TI  - Efficacy and Safety of Lidocaine Infusion Treatment for Neuropathic Pain: A
      Randomized, Double-Blind, and Placebo-Controlled Study.
AB  - BACKGROUND AND OBJECTIVES: Lidocaine infusion therapy (LIT) is an effective
      treatment for relieving neuropathic pain (NeP). However, it remains unclear
      whether pain relief can be sustained through repeated lidocaine infusions. This
      study aimed to determine whether repeated intravenous administration of low-dose
      lidocaine could provide prolonged pain relief in patients with specific NeP
      conditions. METHODS: This is a prospective, randomized, double-blind, placebo
      controlled, parallel study. We compared the efficacy and safety of lidocaine
      infusions (3 mg/kg) in the LIT group and normal saline infusions in the control
      group once a week for 4 consecutive weeks in patients with postherpetic neuralgia
      or complex regional pain syndrome type II. The primary outcome was the difference
      in the percentage change in the 11-point numerical rating scale (NRS) pain score
      from baseline to after the final infusion. Secondary outcomes included pain
      scores during 4 weeks of follow-up and any complications. RESULTS: Forty-two
      patients completed this study protocol. The percentage reduction in NRS pain
      scores after the final infusion was significantly greater in the LIT group
      compared with the control group (P = 0.011). However, this pain reduction was not
      detectable at the 4-week follow-up. The difference in the percentage change in
      NRS pain scores was especially prominent in the LIT group after the third and
      fourth infusions. None of the study participants experienced serious
      complications from the treatment. CONCLUSIONS: Lidocaine infusion therapy (3
      mg/kg of lidocaine administered over 1 hour) provided effective short-term pain
      relief, which was substantially prominent after repeated infusions were
      administered to patients with refractory NeP. CLINICAL TRIAL REGISTRATION: This
      study was registered at ClinicalTrials.gov, identifier NCT02597257.

PMID- 29381571
TI  - Treatment of Spinopelvic Dissociation: A Critical Analysis Review.

PMID- 29381572
TI  - Chagas Disease Recommendations for Solid-Organ Transplant Recipients and Donors.

PMID- 29381573
TI  - Visceral and Cutaneous Leishmaniasis Recommendations for Solid Organ Transplant
      Recipients and Donors.

PMID- 29381574
TI  - Malaria Disease Recommendations for Solid Organ Transplant Recipients and Donors.

PMID- 29381575
TI  - Schistosomiasis and Strongyloidiasis Recommendations for Solid-Organ Transplant
      Recipients and Donors.

PMID- 29381576
TI  - Traveler's Diarrhea Recommendations for Solid Organ Transplant Recipients and
      Donors.

PMID- 29381577
TI  - Arboviruses Recommendations for Solid-Organ Transplant Recipients and Donors.

PMID- 29381578
TI  - Endemic Fungal Infection Recommendations for Solid-Organ Transplant Recipients
      and Donors.

PMID- 29381579
TI  - Tuberculosis Recommendations for Solid Organ Transplant Recipients and Donors.

PMID- 29381580
TI  - Viral Hepatitis Recommendations for Solid-Organ Transplant Recipients and Donors.

PMID- 29381581
TI  - Vaccine Recommendations for Solid-Organ Transplant Recipients and Donors.

PMID- 29381582
TI  - Recommendations for Management of Endemic Diseases and Travel Medicine in Solid
      Organ Transplant Recipients and Donors: Latin America - Map Gallery.

PMID- 29381583
TI  - 99mTc-TRODAT-1 SPECT/CT imaging as a complementary biomarker in the diagnosis of
      parkinsonian syndromes.
AB  - INTRODUCTION: Parkinson's disease (PD) and Parkinson plus syndromes (PPS) are
      neurodegenerative movement disorders caused by loss of dopamine in the basal
      ganglia. The diagnosis of both PD and PPS is complex as it is made solely on the
      basis of clinical features, with no established imaging modality to aid in the
      diagnosis. Technetium-99m-labeled tropane derivative (Tc-TRODAT-1) binds to the
      dopamine transporters present in the presynaptic membrane of the dopaminergic
      nerve terminal. The aim of this prospective study was to investigate the
      potential usefulness of Tc-TRODAT-1 imaging in the diagnosis of PD and PPS.
      PATIENTS AND METHODS: Fifty-eight patients with a clinical diagnosis of
      idiopathic PD or PPS were recruited. The severity of the disease was assessed
      using the Hoehn and Yahr scale. Patients in stage I and II were considered as
      cases of Early PD. Twenty-five apparently healthy volunteers served as controls.
      Brain single-photon emission computed tomography/computed tomography in all the
      participants was performed 3-4 h after an injection of Tc-TRODAT-1. Specific
      uptake ratios (SURs) of striatum were calculated for both the left and right
      striatum, and the values were compared between PD, PPS, and healthy volunteers.
      RESULTS: A significant lower uptake of tracer activity was found in either of the
      striatum in PD and PPS cases compared with the control group, which showed a
      symmetrical comma-shaped striatal uptake. This was also reflected in the SUR
      values, which were significantly higher in the control group in comparison with
      the PD and PPS patients (P<0.001). A significant difference was also found in the
      SUR values between the cases of early PD and control group (P<0.001).No
      significant difference was noted among the SUR values in different Hoehn and Yahr
      stages. CONCLUSION: For clinical practice, both the visual analysis and the
      quantitative parameters of Tc-TRODAT-1 single-photon emission computed
      tomography/computed tomography showed usefulness in distinguishing cases of PD
      and PPS from the healthy individuals.

PMID- 29381584
TI  - Oligometastatic recurrent prostate cancer detects by fluorine-18-choline positron
      emission tomography/computed tomography in patients with prostate-specific
      antigen levels of up to 5 ng/ml.
AB  - PURPOSE: The aim of this study was to assess the ability of fluorine-18
      fluorocholine (F-FCH) PET/computed tomography (CT) to detect oligometastatic
      disease (OMD) in patients with early recurrence of prostate cancer (PC) [prostate
      specific antigen (PSA)<=5 ng/ml]. PATIENTS AND METHODS: Between 2010 and 2016,
      324 patients with PC and PSA levels of less than or equal to 5 ng/ml were
      recruited. The mean (SD) age of the patients was 71 (10) years. All patients were
      treated with a radical prostatectomy+/-lymphadenectomy. One-hundred and twenty
      one patients were under hormonal therapy at the time of PET/CT, whereas 203 were
      not. The mean (SD) PSA at the time of PET/CT was 1.33 (1.19) ng/ml, the mean (SD)
      PSA doubling time (PSAdt) was 10 (12) months, and the mean (SD) PSA velocity
      (PSAvel) was 1.94 (3.31) ng/ml/year. The correlation between continuous and
      categorical data was assessed using Student's t-test or by analysis of variance
      and by the chi-test, respectively. Univariate and multivariate analysis was
      carried out for the identification of clinical variables able to predict the
      presence of OMD. RESULTS: One-hundred and ninety-three patients had a negative F
      FCH PET/CT, whereas 131 (40.4%) had a positive scan. Of these latter patients, 35
      had a significant F-FCH uptake in the prostatic fossae, 59 in the lymph nodes,
      and 37 in bone. PSA levels were significantly different between patients with a
      positive than those with a negative scan (P<0.001). F-FCH PET/CT was negative in
      the majority of patients with a PSA of less than or equal to 1 (63.2%) ng/ml.
      More than 60% of patients with a PSAdt of less than or equal to 6 months had a
      positive F-FCH PET/CT scan for OMD. PSAvel was higher in patients with a positive
      scan than those with a negative finding. At univariate analysis, PSA level,
      PSAdt, and PSAvel were predictors of a positive F-FCH PET/CT for OMD, whereas on
      multivariate analysis, only PSA level and PSAdt were independent predictors (both
      P<0.01). Furthermore, PSAdt was the only independent predictor of OMD at the
      lymph node level. CONCLUSION: In patients with early recurrence of PC, F-FCH
      PET/CT is able to detect OMD in 40% of cases. This finding has an important
      impact on the detection of PC recurrent lesions that could be treated by local
      therapy to achieve long-term survival or cure.

PMID- 29381585
TI  - Clinico-social factors to choose radioactive iodine dose in differentiated
      thyroid cancer patients: an Asian survey.
AB  - OBJECTIVE: This survey was designed to investigate the practice of radioactive
      iodine (RAI) therapy and clinico-social factors related to RAI dose in
      differentiated thyroid cancer (DTC) patients among Asian countries. MATERIALS AND
      METHODS: A survey questionnaire was mailed to Asian Nuclear Medicine physicians
      that addressed the infrastructure, general regulations on RAI therapy, adherence
      to recommendations, RAI dose selection, factors to elevate RAI dose, and follow
      up protocols in DTC patients. Contrived RAI practice recommendations were based
      on key international guidelines. RESULTS: A total of 38 institutes from 20 Asian
      countries were enrolled. Dose administration criterion was 30 mCi, but release
      criterion was variable (5-70 MUSv/h). When the administered RAI dose was
      classified according to three risk stratifications, RAI dose distribution was
      variable, especially in the low-risk group. In this group, 14.0% of respondents
      preferred no ablation, 54.5% were treated with 0-30 mCi, 21.5% were treated with
      30-50 mCi, and 10.0% were administered even higher doses of 80-100 mCi. The major
      factors that influenced the elevated RAI doses in the respondents included high
      serum thyroglobulin (Tg), inadequate information on lymph node involvement, and
      histopathology reporting. Although serum Tg measurement is included in most of
      the institutes as a follow-up tool, neck ultrasound was omitted in 25% and in
      another 25% a whole-body scan was not included. CONCLUSION: Different RAI dose
      ranges are used in the low-risk group probably because the enrolled physicians
      consider RAI dose elevation on the basis of clinico-social factors beyond pre
      existed guidelines. Our study may enable closer harmonization of RAI therapy
      practice in Asian countries.

PMID- 29381586
TI  - Evaluation of 18F-FDG PET-CT as a prognostic marker in advanced biliary tract
      cancer.
AB  - BACKGROUND: Advanced biliary tract cancers have a dismal prognosis. Treatment
      with gemcitabine plus cisplatin has resulted in a significant improvement in
      survival; however, early assessment of outcomes poses a challenge. OBJECTIVE: We
      carried out a prospective study to evaluate the prognostic role of fluorine-18
      fluorodeoxyglucose (F-FDG) PET-CT scans in patients with advanced biliary tract
      cancer. PATIENTS AND METHODS: Patients with advanced unresectable or metastatic
      biliary tract cancer starting first-line chemotherapy with gemcitabine plus
      cisplatin underwent F-FDG PET-CT studies at baseline and after two cycles of
      therapy. The total lesion glycolysis (TLG) measured at baseline as well as the
      variation in TLG between the two studies were analyzed as prognostic indicators
      of overall survival. The survival analyses were carried out using Kaplan-Meier
      curves and the comparison of survival curves was performed using the Breslow
      test. RESULTS: Of the 42 patients included, 37 had the first F-FDG PET-CT and 27
      had the second F-FDG PET-CT. Patients with lower TLG values at baseline or after
      two cycles of therapy presented a higher median survival than patients with
      higher baseline TLG values. Patients with a higher decrease in the TLG values
      between the two studies also had a higher median survival time. However, these
      results only trended for statistical significance (P values ranging between 0.05
      and 0.16). CONCLUSION: Lower baseline TLG measured by F-FDG PET-CT as well as a
      decrease in metabolic uptake after chemotherapy were associated with a trend
      toward longer median survival among patients with advanced biliary cancers.

PMID- 29381587
TI  - Status Quo in Pediatric and Neonatal Simulation in Four Central European Regions:
      The DACHS Survey.
AB  - INTRODUCTION: Simulation has acquired wide acceptance as an important component
      of education in health care and as a key tool to increase patient safety. This
      study aimed at identifying to what extent and how pediatric and neonatal
      simulation-based training (SBT) was being carried out in four Central European
      regions. METHODS: We surveyed all pediatric and neonatal health care institutions
      in Germany, Austria, Switzerland, and South Tyrol on their current state of SBT
      using an online questionnaire. RESULTS: We dispatched 440 questionnaires with a
      45.9% response rate. Sixty-one percent (61.4%) of institutions performed SBT
      (algorithm training, 87.4%; skill training, 62.2%; high-fidelity SBT, 56.8%).
      Training was conducted interprofessionally at 88.9% of surveyed institutions.
      Physicians and nurses most often received SBT once per year. Lack of financial
      (62.2%) and personnel (54.1%) resources were the most frequent impediments to
      establish SBT. CONCLUSIONS: Although delivered heterogeneously, widespread use of
      pediatric simulation and a considerable number of already existing SBT programs
      are the key findings of this survey. These data are encouraging enough to promote
      more effective networking in simulation-based research, education, training, and
      quality improvement, as we aim to ultimately increase patient safety for
      neonates, infants, and children.

PMID- 29381588
TI  - Three-Dimensional Printed Pediatric Airway Model Improves Novice Learners'
      Flexible Bronchoscopy Skills With Minimal Direct Teaching From Faculty.
AB  - INTRODUCTION: Training in pediatric flexible bronchoscopy (FB) is predominantly
      completed on patients. Early trainees are less accurate and slower than
      experienced bronchoscopists. This report describes the development of a three
      dimensional printed airway model and describes how the model was used to teach
      learners basic FB skills. METHODS: Postgraduate year two (PGY2) pediatric
      residents completing a 1-month pediatric pulmonology rotation with minimal
      previous exposure to FB were randomized into a simulation trainee group (n = 18)
      or a control resident group (n = 9). The simulation group received four 15-minute
      practice sessions (3 self-directed, 1 with feedback). Participants completed a
      bronchoscopy assessment on the model at prestudy, poststudy, and delayed (at
      least 2 months after the rotation) time points. Outcomes were identification of
      markers located in the six lung areas and completion time. RESULTS: There was no
      difference in prestudy scores between groups. In the poststudy assessment, the
      simulation participants correctly identified more lung area markers (median = 6
      vs 1.5, P < 0.001) and were faster (median = 102 vs 600 seconds, P < 0.001). In
      the delayed assessment, correct marker identification trended toward improvement
      in the simulation group compared with controls (median = 4 vs 2, P = 0.077).
      CONCLUSIONS: With 1 hour of practice time, requiring 15 minutes of direct
      teaching, novice resident bronchoscopists are able to more accurately identify
      and visualize the five lung lobes and lingula via FB and are able to do so in
      less time than control residents. This anatomically accurate model could be used
      to train basic FB skills at a low cost compared with other models.

PMID- 29381589
TI  - Exploring Faculty Approaches to Feedback in the Simulated Setting: Are They
      Evidence Informed?
AB  - INTRODUCTION: Feedback in clinical education and after simulated experiences
      facilitates learning. Although evidence-based guidelines for feedback exist,
      faculty experience challenges in applying the guidelines. We set out to explore
      how faculty approach feedback and how these approaches align with current
      recommendations. METHODS: There is strong evidence for the following four
      components of feedback: feedback as a social interaction, tailoring content,
      providing specific descriptions of performance, and identifying actionable items.
      Faculty preceptors participated in feedback simulations followed by debriefing.
      The simulations were video recorded, transcribed, and analyzed qualitatively
      using template analysis to examine faculty approaches to feedback relative to
      evidence-informed recommendations. RESULTS: Recorded encounters involving 18
      faculty and 11 facilitators yielded 111 videos. There was variability in the
      extent to which feedback approaches aligned with recommended practices. Faculty
      behaviors aligned with recommendations included a conversational approach,
      flexibly adapting feedback techniques to resident context, offering rich
      descriptions of observations with specific examples and concrete suggestions,
      achieving a shared understanding of strengths and gaps early on to allow
      sufficient time for problem-solving, and establishing a plan for ongoing
      development. Behaviors misaligned with guidelines included prioritizing the task
      of feedback over the relationship, lack of flexibility in techniques applied,
      using generic questions that did not explore residents' experiences, and ending
      with a vague plan for improvement. CONCLUSIONS: Faculty demonstrate variability
      in feedback skills in relation to recommended practices. Simulated feedback
      experiences may offer a safe environment for faculty to further develop the
      skills needed to help residents progress within competency-based medical
      education.

PMID- 29381590
TI  - Simulation of Shoulder Dystocia for Skill Acquisition and Competency Assessment:
      A Systematic Review and Gap Analysis.
AB  - STATEMENT: Mastery of shoulder dystocia management skills acquired via simulation
      training can reduce neonatal brachial plexus injury by 66% to 90%. However, the
      correlation between simulation drills and reduction in clinical injuries has been
      inconsistently replicated, and establishing a causal relationship between
      simulation training and reduction of adverse clinical events from shoulder
      dystocia is infeasible due to ethical limitations. Nevertheless, professional
      liability insurance carriers increasingly are mandating simulation-based
      rehearsal and competency assessment of their covered obstetric providers'
      shoulder dystocia management skills-a high-stakes demand that will require rapid
      scaling up of access to quality shoulder dystocia simulation. However, questions
      remain about differing simulation training schemes and instructional content used
      among clinically effective and ineffective educational interventions. This review
      of original research compares curricular content of shoulder dystocia simulation
      and reveals several critical gaps: (1) prescriptive instruction prioritizing
      maneuvers shown to decrease strain on the brachial plexus is inconsistently used.
      (2) Proscriptive instruction to avoid placing excessive and laterally directed
      traction on the head or to observe a brief hands-off period before attempting
      traction is infrequently explicit. (3) Neither relative effectiveness nor
      potential interaction between prescriptive and proscriptive elements of
      instruction has been examined directly. (4) Reliability of high-fidelity
      mannequins capable of objective measurement of clinician-applied traction force
      as compared with subjective assessment of provider competence is unknown. Further
      study is needed to address these gaps and inform efficient and effective
      implementation of clinically translatable shoulder dystocia simulation.

PMID- 29381591
TI  - Anaesthesiology and ethics: Can the anaesthesiologist ameliorate simply and
      rapidly the assessment of decision-making capacity in the elderly?

PMID- 29381592
TI  - History of anaesthesia: Nurse anaesthesia practice in the G7 countries (Canada,
      France, Germany, Italy, Japan, the United Kingdom and the United States of
      America).
AB  - : Many factors determine whether nurses, physicians or both administer
      anaesthesia in any country. We examined the status of nurse-administered
      anaesthesia in the Group of Seven (G7) countries (Canada, France, Germany, Italy,
      Japan, the United Kingdom and the United States of America) and explored how
      historical factors, mixing global and local contexts (such as professional
      relations, medical and nursing education, social status of nurses, demographics
      and World Wars in the 20th century), help explain observed differences. Nearly
      equal numbers of physicians and nurses are currently engaged in the delivery of
      anaesthesia care in the United States but, remarkably, although the introduction
      or re-introduction of nurse anaesthesia in the 20th century was attempted in all
      the other G7 countries (except Japan), it has been successful only in France
      because of the cooperation with the United States during World War II.

PMID- 29381593
TI  - Emergency medicine is about collaboration, not monopolisation.

PMID- 29381594
TI  - Reply to: emergency medicine is about collaboration, not monopolisation.

PMID- 29381595
TI  - Who takes the lead in critically ill patients?

PMID- 29381596
TI  - Reply to: who takes the lead in critical illness?

PMID- 29381597
TI  - Professionalisation rather than monopolisation is the future of emergency
      medicine in Europe.

PMID- 29381598
TI  - Reply to: professionalisation rather than monopolisation is the future of
      emergency medicine in Europe.

PMID- 29381599
TI  - Collaboration in emergency medical care in Europe: the patient is the winner.

PMID- 29381600
TI  - Reply to: collaboration in emergency medical care in Europe: the ten principles
      of CRitical Emergency Medicine (CREM).

PMID- 29381601
TI  - Open Globe Injury: Demographic and Clinical Features.
AB  - BACKGROUND: Open globe injuries (OGIs) are the main cause of visual impairment
      worldwide. The aim of this study was to evaluate the clinical features and the
      visual outcome of OGIs presented to the largest Teaching Hospital in Western part
      of Turkey. METHODS: The study included patients presented with OGI between Jan
      2009 and Dec 2013. Data including patient demographics, causes of injury, visual
      acuity (VA) at presentation, and final VA were collected. Ocular Trauma Scores
      (OTS) were calculated. Statistical analyses were performed to identify prognostic
      factors. RESULTS: One hundred fifty-nine eyes of 156 patients with OGIs were
      included. The mean age was 36.89 +/- 20.07 years. Significant male predominance
      was noted (77.6%). Domestic (28.3%) and work-related (22%) accidents were the
      most common causes of all OGIs. While some improvement in best corrected visual
      acuity (BCVA) after treatment has been noted in 68 eyes (55.7%), the final BCVA
      was equal to or worse than the initial BCVA in 54 eyes (44.3%). According to the
      OTS and final BCVA associations in our study, while the eyes with OGI included in
      OTS category 1 and 2 (n = 84) consist of 68.8% of all the OGI cases, 48.8% (n =
      41) of them were classified as having a poor visual outcome. All of the eyes in
      OTS category 3 and 4 cases (n = 38) (31.2% of all the OGI cases) showed good
      visual outcome. CONCLUSION: Some clinical features may have a potential to
      correctly predict final visual outcomes. Although the OTS has not been fully
      validated yet, it could potentially be one of the best indicators available for
      the prognosis in OGI.

PMID- 29381602
TI  - A Practical Suggestion for Prepare Dorsal Onlay Graft.
AB  - Nowadays, rhinoplasty is one of the most popular surgical procedures. Dorsal
      contour irregularities caused by various maneuvers, such as hump resection, are a
      major concern in patients who have undergone rhinoplasty. The most common graft
      used in this case is dorsal onlay graft which is made from sliced and crushed
      cartilage. Ear, nose and throat specialists usually use Swester table (mayo desk)
      for preparing the graft, if there is no other steril metal instrument. Crushed
      cartilage is done on a sterile gauze or on the tables' cover, as a result
      cartilage may be contaminated with particules from the tables' cover and sterile
      gauze.The authors recommend using the steril pack of a new sterilized surgical
      instrument opened on the table for the slicing or crushing process. In this way,
      the cartilage can be spared from contamination and the loss of some cartilage to
      the table during slicing or crushing can be prevented.

PMID- 29381603
TI  - The Impact of Velopharyngeal Surgery on the Polysomnographic Parameters After
      Cleft Palate Repair.
AB  - Velopharyngeal surgical procedures may have adverse effect on the airway of the
      patients with velopharyngeal insufficiency (VPI). The aim of this study was to
      evaluate the polysomnographic parameters (PSG) in patients who underwent
      corrective surgery for treatment of VPI. The study included 39 patients who
      underwent 1 of 3 velopharyngeal surgical techniques; Furlow palatoplasty (12
      patients), pharyngeal flap (18 patients), and sphincter pharyngoplasty (9
      patients). The patients were subjected to PSG, and they were considered to have
      obstructive sleep apnea (OSA) with apnea-hypoapnea index (AHI) >1.Comparison of
      PSG parameters of patients showed insignificant difference regarding the total
      sleep time, sleep efficiency, arousal index, desaturation index, and minimum
      oxygen saturation. Significant difference was detected regarding peak end-tidal
      CO2 and AHI. Pharyngeal flap was detected as the most surgical technique that
      worsened the PSG parameters with OSA in 78% of patients, followed by sphincter
      pharyngoplasty with OSA in 56% of patients. Furlow palatoplasty was detected as
      the least impacting technique on the airway in 25% of patients who demonstrated
      OSA. In conclusion, velopharyngeal surgery has a variable impact on the PSG;
      pharyngeal flap has the most worsening effect followed by sphincter
      pharyngoplasty, while Furlow palatoplasty has the least adverse effect.

PMID- 29381604
TI  - Cochlear Implantation in Postmeningitic Deafness.
AB  - PURPOSE: The aim of this study is to evaluate long-term outcomes of cochlear
      implantation (CI) in patients with postmeningitic deafness. METHODS: Twenty-seven
      patients with severe to profound hearing loss due to bacterial meningitis and
      received CI were the subjects of this study. Surgical findings and long-term
      audiological performances were evaluated. Speech perception and speech
      intelligibility of the implanted patients were evaluated with the categories of
      auditory performance-II (CAP-II) test and speech intelligibility rating (SIR)
      test, respectively. RESULTS: Eighteen of the 27 patients had received full
      electrode insertion through the patent cochlear lumen. Remaining 9 patients had
      varying degrees of ossification throughout the cochlea and needed to be drilled
      to achieve partial electrode insertion. None of the patients exhibited surgical
      complication. Scores in both test batteries (CAP-II and SIR) were comparable
      between patients who received full or partial electrode insertion (P > 0.05).
      CONCLUSION: Cochlear implantation after postmeningitic deafness has favorable
      outcomes especially in long term. Although this type of inner ear pathology may
      require special considerations during surgery, it is a relatively safe procedure.

PMID- 29381605
TI  - Novel PTCH1 Gene Mutation in Nevoid Basal Cell Carcinoma Syndrome.
AB  - The purpose of this study was to report clinical characteristics, surgical
      results, and new PTCH1 gene mutations in nevoid basal cell carcinoma syndrome
      (NBCCS). Five patients were referred to the Department of Oral and Maxillofacial
      Surgery from local dental clinics between 2006 and 2016 to treat multiple
      keratocystic odontogenic tumors (KOTs). The cystic lesions were enucleated and
      peripheral ostectomy was performed to obtain safety margin. Recurrence and/or de
      novo development of KOT were assessed. Gene analysis using peripheral blood was
      performed in all patients to identify the mutation of PTCH1 gene. Three patients
      showed familial history of first-degree relatives. Of the major criteria, all
      patients presented KOT but only 1 patient had basal cell carcinoma. Of the minor
      criteria, 4 of the 5 patients presented macrocephaly and hypertelorism. During
      follow-up periods, all patients showed recurrence and/or de novo development of
      KOT in the jaw bone. Mutation analysis of PTCH1 gene showed 3 frameshifts
      (c.817_818ins(T), c.1226_1227ins(A), and c.2748del(C)), 1 splicing (c.1504-2A>T),
      and 1 missense (c.385T>C) mutation. Mutations were found in exon 1, 6, 9, 17, and
      intron 10. Regular follow-up is necessary because recurrence rate of KOT was very
      high. To help early diagnosis, it is essential to routinely perform genetic
      testing to detect PTCH1 gene mutations among patients with NBCCS.

PMID- 29381606
TI  - Endoscopic Anatomic Study Via Grinding Partial Petrous Ridge to the Middle Fossa
      in Retromastoid Keyhole Approach.
AB  - OBJECTIVE: This study aimed to observe the range of exposure, indications, and
      feasibility of the retromastoid keyhole approach via grinding partial petrous
      ridge to the middle fossa. METHODS: Simulated endoscopic surgeries via grinding
      suprameatal tubercle and petrous ridge to expose the middle fossa in retromastoid
      keyhole approach were performed on 8 adult cadaver heads (16 sides) fixed by
      formalin. The maximum exposure range in endoscope was observed. The boundaries of
      Parkinson triangle and the anatomic structures contained by Meckel cave and
      cavernous sinus (CS) lateral wall were revealed. The distances from midpoint of
      sigmoid sinus posterior border to every important anatomic structures in the
      middle fossa and the length of all sides of Parkinson triangle were measured.
      RESULTS: By using endoscope, the exposure of the cerebellopontine angle,
      ventrolateral brainstem, incisure of tentorium, petroclival region, and CS
      lateral wall were satisfactory. Many important anatomic structures in middle
      fossa were exposed well. The distances from midpoint of posterior border of
      sigmoid sinus to suprameatal tubercle, trigeminal semilunar ganglion, posterior
      curve segment of internal carotid artery were 34.42 +/- 2.14, 54.52 +/- 2.87, and
      65.15 +/- 3.13 mm. The lengths of all sides of Parkinson triangle were 18.97 +/-
      2.93, 16.23 +/- 2.02, and 8.04 +/- 2.34 mm. CONCLUSION: The retromastoid keyhole
      approach via grinding partial petrous ridge to the middle fossa by using
      endoscope can increase the exposure of middle fossa effectively, which is proper
      for most lesions in posterior cranial fossa while some parts extend to middle
      fossa.

PMID- 29381607
TI  - Nickel-Titanium Wire as Suture Material: A New Technique for the Fixation of
      Skin.
AB  - PURPOSE: To introduce nickel-titanium wire as suture material for closure of
      incisions in cleft lip procedures. METHOD: Closure of skin incisions using nickel
      titanium wire as suture material, with postoperative follow-up wound evaluation.
      RESULTS: There was excellent patient satisfaction and good cosmetic outcome.
      CONCLUSION: Nickel-titanium wire is an excellent alternative for suture closure
      of cleft lip surgical incisions.

PMID- 29381608
TI  - Treatment of Sagittal Fracture of the Zygomatic Arch Root Assisted by Surgical
      Navigation Technology.
AB  - Sagittal fracture at the temporal root of the zygomatic arch often occurs as a
      part of zygomaticomaxillary fractures. The authors described the application of
      computer-assisted navigation in the lag screw insertion for the fixation of
      sagittal fracture at the temporal root of zygomatic arch. Using the presurgical
      planning of the computer-assisted navigation system, the trajectory of lag screw
      insertion was designed, and the insertion depth was calculated. In the
      presurgical planning, the trajectory of screw insertion was placed with an
      anterior inclination of 10 degrees  to 15 degrees  (mean: 12.24 degrees ), and
      the screw insertion depth was 9.0 to 12.0 mm (mean: 10.65 mm). In the operation,
      the screw insertion in the fixation of the sagittal fracture was performed under
      the guidance of navigation system according to the presurgical planning. The
      postoperative CT scan showed exact reduction and fixation of the sagittal
      fracture in all cases. Computer-assisted navigation is a useful tool for the lag
      screw insertion in the precise fixation of sagittal fracture at the temporal root
      of the zygomatic arch in complex zygomaticomaxillary fractures.

PMID- 29381609
TI  - Morphometric Measurements of Bony Nasolacrimal Canal in Children.
AB  - OBJECTIVE: Morphology and dimensions of the bony nasolacrimal canal duct (BNLD)
      as a key factor in the development of primary acquired nasolacrimal duct
      obstruction. We aimed to obtain detailed morphometric analysis of BNLD in
      children without nasolacrimal duct pathology by using computed tomography and
      provide standard measurements by means of age which could be utilized in planning
      management or in invasive interventions. METHODS: Picture Archiving Communication
      Systems database of our hospital's radiology department was searched for this
      retrospective study. Subjects were under 18 years of age who had undergone a
      paranasal, maxillofacial, or temporal bone high-resolution computed tomography
      scan in last 2 years with various indications. Those with fractures including
      facial bones and/or nasolacrimal canal or history of nasolacrimal duct pathology
      were excluded from the study. We measured the diameter, angle, and surface area
      of BNLD. RESULTS: A total number of 136 subjects (86 boys, 50 girls) were
      included in the study. The average age was 7.3 +/- 5.1 years. We documented
      statistically significantly positive correlation between all measured diameters
      and ages (P < 0.001), whereas there was a negative association between mean angle
      and age (P < 0.001). Mean angle is defined as the angle between BNLD and nasal
      floor. The surface area of BNLD was found to be significantly increasing
      depending on age (P < 0.001). However, we could not find any significant
      association between gender and measured parameters (P > 0.050). CONCLUSION: Our
      study demonstrated that development of BNLD continues during childhood,
      regardless of gender.

PMID- 29381610
TI  - Facial Fractures.
AB  - AIMS AND OBJECTIVES: The aim of this study is to retrospectively analyze the
      incidence of facial fractures along with age, gender predilection, etiology,
      commonest site, associated dental injuries, and any complications of patients
      operated in Craniofacial Unit of SDM College of Dental Sciences and Hospital.
      MATERIALS AND METHODS: This retrospective study was conducted at the Department
      of OMFS, SDM College of Dental Sciences, Dharwad from January 2003 to December
      2013. Data were recorded for the cause of injury, age and gender distribution,
      frequency and type of injury, localization and frequency of soft tissue injuries,
      dentoalveolar trauma, facial bone fractures, complications, concomitant injuries,
      and different treatment protocols.All the data were analyzed using statistical
      analysis that is chi-squared test. RESULTS: A total of 1146 patients reported at
      our unit with facial fractures during these 10 years. Males accounted for a
      higher frequency of facial fractures (88.8%). Mandible was the commonest bone to
      be fractured among all the facial bones (71.2%). Maxillary central incisors were
      the most common teeth to be injured (33.8%) and avulsion was the most common type
      of injury (44.6%). Commonest postoperative complication was plate infection (11%)
      leading to plate removal. Other injuries associated with facial fractures were
      rib fractures, head injuries, upper and lower limb fractures, etc., among these
      rib fractures were seen most frequently (21.6%). CONCLUSION: This study was
      performed to compare the different etiologic factors leading to diverse facial
      fracture patterns. By statistical analysis of this record the authors come to
      know about the relationship of facial fractures with gender, age, associated
      comorbidities, etc.

PMID- 29381611
TI  - Decannulation and Airway Outcomes With Maxillomandibular Distraction in Treacher
      Collins and Nager Syndrome.
AB  - BACKGROUND: Treacher Collins syndrome is a rare disorder (1/50,000 live births)
      with features that include hypoplastic orbitozygomatic complex with downward
      slanting eyes, and maxillary/mandibular retrusion. Obstructive sleep apnea and
      tracheostomy-dependence are common. This study presents the outcomes of skeletal
      distraction on avoidance of tracheostomy and decannulation in this patient
      population. METHODS: The authors reviewed charts of all patients with Treacher
      Collins syndrome who underwent craniofacial reconstruction from 2003 to 2016.
      Primary outcome measures included decannulation of tracheostomy dependent
      patients and avoidance of tracheostomy. Secondary outcome measures included
      cephalometric parameters, polysomnography scores, and airway exposure scores on
      direct laryngoscopy. RESULTS: Twenty-five patients underwent mandibular and
      maxillary advancement to resolve upper airway obstruction. Mandibular distraction
      was performed in 24 of 25 patients, and maxillary distraction in 14 of 25
      patients. Maxillary distraction was combined with mandibular distraction in 13 of
      17 to accomplish greater advancement and counter-clockwise rotation of the entire
      maxillary-mandibular complex. Six of 7 patients, 85.7%, avoided a tracheostomy
      and 39% (7 of 18) were decannulated. Cephalometric changes in sella-nasion-A
      point, sella-nasion-B , occlusal plane angle, and posterior airway space were
      equivalent between the groups who were able to clear their obstruction and those
      who were not. CONCLUSIONS: Treacher Collins is a very challenging disease in
      which to resolve airway obstruction. Thus, thorough evaluation of the entire
      airway for all levels of obstruction is critical to successful outcomes. Future
      collaborative efforts between multiple institutions can help to increase our
      understanding and effective management of this rare disease.

PMID- 29381612
TI  - Treatment of Mandibular Ameloblastoma Involving the Mandibular Condyle: Resection
      and Concomitant Reconstruction With a Custom Hybrid Total Joint Prosthesis and
      Iliac Bone Graft.
AB  - AIM: To describe the treatment of ameloblastoma involving the mandibular body and
      condyle in 3 patients. METHODS: This report describes 3 patients with large
      ameloblastomas (2 were second recurrences) treated by partial mandibular
      resection. Involvement of the mandibular condyle in these 3 patients made the
      reconstruction more challenging. Reconstruction included immediate
      temporomandibular joint replacement by a custom-made alloplastic total joint and
      mandibular body (Zimmer-Biomet, Jacksonville, FL). These devices were designed
      using virtual surgical planning software. The 3 patients underwent concomitant
      bone graft reconstruction using autogenous-free corticocancellous block bone
      grafts from the iliac crest. This facilitated later dental implant placement and
      full dental rehabilitation. Direct inferior alveolar nerve repair or nerve graft
      reconstruction with allograft was also carried out for all 3 patients.
      Maxillomandibular fixation was not used in all 3 patients. RESULTS: All the 3
      patients underwent successful surgery and recovery. Mandibular function was
      preserved. The concomitant bone graft allowed successful dental implant placement
      for subsequent planned restorative dentistry. CONCLUSION: Ameloblastoma involving
      the mandibular condyle can be successfully treated by resection and concomitant
      total joint replacement with an alloplastic device. This technique shows promise
      in that there is rapid return to excellent function thanks to rigid fixation of
      the construct. Mirroring software used in the prosthesis design facilitates
      excellent cosmetic outcomes.

PMID- 29381613
TI  - Trismus in Face Transplantation Following Ballistic Trauma.
AB  - BACKGROUND: Trismus can be a challenging consequence of ballistic trauma to the
      face, and has rarely been described in the setting of face transplantation.
      Almost half of all current face transplant recipients in the world received
      transplantation to restore form and function after a ballistic injury. Here we
      report our experience and challenges with long standing trismus after face
      transplantation. METHODS: We reviewed the medical records of our face transplant
      recipients whose indication was ballistic injury. We focused our review on
      trismus and assessed the pre-, peri- and postoperative planning, surgery and
      functional outcomes. RESULTS: Two patients received partial face transplantation,
      including the midface for ballistic trauma. Both patients suffered from impaired
      mouth opening, speech intelligibility, and oral competence. Severe scarring of
      the temporomandibular joint (TMJ) required intraoperative release in both
      patients, and additional total condylectomy on the left side 6 months
      posttransplant for 1 patient. Posttransplant, both patients achieved an
      improvement in mouth opening; however, there was persistent trismus. One year
      after transplantation, range of motion of the jaw had improved for both patients.
      Independent oral food intake was possible 1 year after surgery, although spillage
      of liquids and mixed consistency solids persisted. Speech intelligibility testing
      showed impairments in the immediate postoperative period, with improvement to
      over 85% for both patients at 1 year posttransplant. CONCLUSIONS: Ballistic
      trauma to the face and subsequent reconstructive measures can cause significant
      scarring and covert injuries to structures such as the TMJ, resulting in long
      standing trismus. Meticulous individual planning prior to interventions such as
      face transplantation must take these into account. We encourage intraoperative
      evaluation of these structures as well as peri- and postoperative treatment when
      necessary. Due to the nature of the primary injury, functional outcomes after
      face transplantation in these patients may differ substantially from those of
      other indications.

PMID- 29381614
TI  - Bone-Conditioned Medium Obtained From Calvaria, Mandible, and Tibia Cause an
      Equivalent TGF-beta1 Response In Vitro.
AB  - Bones with different embryological origin and mode of ossification are supposed
      to vary in their capacity for supporting graft consolidation. The aim of the
      current pilot study was to assess the TGF-beta1 activity of bone chips obtained
      from distinct anatomic locations. Conditioned medium was prepared from bone chips
      harvested from pig calvaria, mandible, and tibia. Human oral fibroblasts were
      exposed to bone-conditioned medium (BCM) followed by reverse transcriptase
      polymerase chain reaction of the TGF-beta1 target genes. Also an immunoassay for
      interleukin 11 (IL-11) and TGF-beta1 was performed. The impact of BCM on alkaline
      phosphatase activity was determined with murine MC3T3-E1 osteogenic cells. The
      authors report here that BCM contains TGF-beta1 in the ng/mL range. Bone chips
      prepared from pig calvaria, mandible, and tibia femur had a similar capacity for
      increasing the expression of the TGF-beta1 target genes IL-11, NOX4, and PRG4.
      Correspondingly, immunoassays revealed similar production of IL-11 by human oral
      fibroblasts. Furthermore, conditioned medium obtained from the 3 bones decreased
      alkaline phosphatase activity in MC3T3-E1 osteogenic cells. These preliminary
      data demonstrate that particulated bone grafts, regardless of embryological
      origin, mode of ossification and morphology, release a similar TGF-beta1
      activity.

PMID- 29381615
TI  - Posterior Vault Distraction Osteogenesis in Nonsyndromic Patients: An Evaluation
      of Indications and Safety.
AB  - PURPOSE: The purpose of this study was to evaluate the indications, safety, and
      short-term outcomes of posterior vault distraction osteogenesis (PVDO) in
      patients with no identified acrocephalosyndactyly syndrome (study) and to compare
      those to a syndromic cohort (controls). METHODS: Demographic and perioperative
      data were recorded and compared across the study and control groups for those who
      underwent PVDO between January 2009 and December 2016. Univariate analysis was
      conducted using chi and Fisher exact tests for categorical variables, and Mann
      Whitney U test for continuous variables. RESULTS: Sixty-three subjects were
      included: 19 in the nonsyndromic cohort, 44 in the syndromic cohort. The cohorts
      had similar proportion of subjects exhibiting pansynostosis (42.1% of
      nonsyndromic versus 36.4% of syndromic, P = 0.667). The nonsyndromic cohort was
      significantly older (4.04 +/- 3.66 years versus 2.55 +/- 3.34 years, P = 0.046)
      and had higher rate of signs of raised intracranial pressure (68.4% versus 25.0%,
      P = 0.001) than the syndromic cohort. There was no significant difference in
      perioperative variables or rate of complications (P > 0.05). The mean total
      advancement distance achieved was similar, 27 +/- 6 mm in the nonsyndromic versus
      28 +/- 8 mm in the syndromic cohort (P = 0.964). All nonsyndromic subjects with
      signs of raised intracranial pressure demonstrated improvement at an average
      follow-up of 22 months. CONCLUSION: As in the syndromic patient, PVDO is a safe
      and, in the short-term, effective modality for cranial vault expansion in the
      nonsyndromic patient. The benefits and favorable perioperative profile of PVDO
      may therefore be extended to patient populations other than those with syndromic
      craniosynostosis.

PMID- 29381616
TI  - Spring-Mediated Cranioplasty in Sagittal Synostosis: Does Age at Placement Affect
      Expansion?
AB  - PURPOSE: The aim of this study is to evaluate the effect of timing of surgery and
      spring characteristics on correction of scaphocephalic deformity in patients
      undergoing spring-mediated cranioplasty (SMC) for sagittal craniosynostosis.
      METHODS: The authors conducted a review of patients with sagittal
      craniosynostosis who underwent SMC at a tertiary referral center between July
      2011 and March 2017, with a primary outcome measure of head shape, both
      preoperatively and postoperatively, determined by cephalic index (CI). Patient
      demographics and operative details including timing of surgery and spring
      characteristics were collected. Differences in CI preoperation and postoperation
      were compared using Wilcoxon signed-rank test. Ordinary least-squares linear
      regression was used to assess the impact of timing, number of springs, maximum
      single spring force, and total spring force on postoperative change in CI.
      RESULTS: Thirty-six subjects (12 males and 24 females) were included in the
      study. Mean age at spring placement was 3.9 months (range: 1.9-9.2) with a mean
      follow-up of 1.4 years (range: 0.3-5.2). The mean number of springs used was 3
      (range: 2-4). The mean maximum single spring force was 9.9 Newtons (N) (range:
      6.9-13.0) and the mean total spring force was 24.6 N (range: 12.7-37.0). Mean CI
      increased from 70 +/- 0.9 preoperatively to 77 +/- 1.0 postoperatively (P <
      0.001). Age at spring placement was significantly associated with change in CI:
      for every month increase in age, the change in CI decreased by 1.3 (P = 0.03).
      The number of springs used, greatest single spring force, and total spring force
      did not correlate with changes in CI (P = 0.85, P = 0.42, and P = 0.84,
      respectively). CONCLUSION: In SMC, earlier age at time of surgery appears to
      correlate with greater improvement in CI, at least in the short-term. While
      spring characteristics did not appear to affect head shape, it is possible that
      the authors were underpowered to detect a difference, and spring-related
      variables likely deserve additional study.

PMID- 29381617
TI  - Quantification of Surgical Route Parameters for Exposure of the Jugular Foramen
      Via a Trans-Mastoidal Approach Exposing Jugular Foramen in Three-Dimensional
      Visualization Model.
AB  - OBJECTIVE: Surgical operation within the region of the jugular foramen presents a
      great challenge. The authors characterized the quantitative impact of surgical
      window parameters on the exposure of the jugular foramen via a trans-mastoidal
      approach. METHODS: Computed tomography and magnetic resonance imaging data were
      used to establish a 3-dimensional model of the jugular foramen region. The
      mastoidale, posterior edge of the mastoid, and the superior edge of the bony
      external acoustic meatus were selected as points a, b, and c. The anterior edge
      of the tuberculum jugulare was selected as point d. The midpoints of line
      segments ab, ac, and bc were selected as points e, f, and g. Triangle abc was
      divided into triangles aef, beg, cfg, and efg. Surgical corridors of the
      triangular pyramid were outlined by connecting the above triangles to point d.
      Anatomic exposure was evaluated by measuring the area and volume of various
      structures within each route. Statistical comparisons were performed via analysis
      of variance. RESULTS: The model allowed for adequate visualization of all
      structures. The areas of triangles beg and efg were greater than those of
      triangles aef and cfg (P < 0.05). The volumes of triangular pyramids d-beg and d
      cfg were greater than those of triangular pyramids d-aef and d-efg (P = 0.000).
      Statistically significant differences were also observed for volumes of osseous,
      venous, and cranial nerve structures in all divided routes (P = 0.000).
      CONCLUSION: Our results indicate that 3-dimensional modeling may aid in the
      quantification of surgical exposure and that division of the craniotomy window
      may allow for more precise operation.

PMID- 29381618
TI  - Cone-Beam Computed Tomography-Based Three-Dimensional McNamara Cephalometric
      Analysis.
AB  - This article introduces a method that extends the McNamara cephalometric analysis
      to produce 3-dimensional (3D) measurement values from cone-beam computed
      tomography images. In the extended method, the cephalometric landmarks are
      represented by 3D points; the bilateral cephalometric landmarks are identified on
      both sides of the skull; the cephalometric lines, with the exception of the
      facial axis, are represented by 3D lines; the cephalometric planes, with the
      exception of the facial plane, are represented by planes; the effective
      mandibular length, the effective midfacial length, and the lower anterior facial
      height are measured as 3D point-to-point distances; the nasion perpendicular to
      point A, the pogonion to nasion perpendicular, the upper incisor to point A
      vertical, and the lower incisor to point A-pogonion line are measured each as
      components of a vector; the facial axis angle is measured as a line-to-plane
      angle; and the mandibular plane angle is measured as a plane-to-plane angle. As a
      result, the method provides real effective lengths of the maxilla and mandible on
      both sides of the skull; real height of the lower anterior face; directed
      distances from the point A to the nasion perpendicular, from the pogonion to the
      nasion perpendicular, from the left and right upper incisor to the point A
      vertical, and from the left and right lower incisor to the point A-pogonion line
      for both the lateral and posteroanterior views of the skull; and real angles of
      the facial axis and the mandibular plane. Additionality, the method enables the
      identification of craniofacial asymmetries.

PMID- 29381620
TI  - Modified Methods of Fabricating Helix and Antihelix in Total Auricular
      Reconstruction Based on Different Length of Eighth Costal Cartilage.
AB  - BACKGROUND: Attaining an ideal appearance of the reconstructed ear depends
      primarily on the fabricated cartilaginous ear framework. Despite the role of
      eighth costal cartilage, the length of the eighth rib cartilage is difficult to
      anticipate, and growth of the eighth cartilage is variable. The authors discussed
      modified methods of fabricating helix and antihelix based on different length of
      eighth costal cartilage. METHODS: Based on the actual length of the eighth costal
      cartilage, patients were divided into group A and group B. In group A, the eighth
      costal cartilage was divided into 2 parts. Part I was used to fashion the helix,
      whereas part II was used to fabricate the antihelix and superior crus. In group
      B, the seventh costal cartilage was cut into 3 parts. Part I and part II were
      used to fashion the helix, antihelix, and superior crus as group A did. Part III
      was assembled to the lateral part of the framework to form the inferior crus.
      RESULTS: A total of 56 patients underwent auricular reconstruction adopting the
      modified techniques between 2015 and 2016. Three cases have been selected to
      illustrate the favorable result achieved. They revealed that the helix,
      antihelix, superior crus, and inferior crus all appeared distinct and presented a
      favorable result of the contour of the reconstructed auricle. CONCLUSIONS: Based
      on different length of eighth costal cartilage, modified methods of fabricating
      helix and antihelix make full use of the autogenous costal cartilage, elevate
      anatomical details, and enhance the overall aesthetics of reconstructed ear. The
      great majority of patients have satisfactory surgical outcomes, demonstrating
      that personalized treatment is necessary.

PMID- 29381619
TI  - Intralesional Bleomycin Injection for Propranolol-Resistant Hemangiomas.
AB  - Propranolol has been the first-line treatment for alarming hemangiomas. However,
      some hemangiomas are propranolol-resistant. The authors reported 1 propranolol
      resistant hemangioma which was treated with intralesional bleomycin injections.
      Sixteen months after 3 injections, the lesion still remained stable. Its
      potential mechanism was clarified by ultrasonic monitoring. Intralesional
      bleomycin injection can be considered an ideal option in treating propranolol
      resistant hemangiomas.

PMID- 29381621
TI  - Longitudinal Study of Scar Hyperplasia Formation Following Cleft Lip Wound
      Healing.
AB  - The purpose of this study was to observe the hyperplasia trend of scar after the
      cleft lip surgery in a rabbit animal model, and determine the time-point of the
      highest hypertrophic degree of scar after cleft lip repair. Forty New Zealand
      white rabbits from the same offspring were used to establish a cleft lip wound
      healing model using Millard surgery procedure. The scar volumes were measured and
      granulation tissues were observed visually in the 2, 3, 4, and 5 weeks after
      operation. The scar tissues were harvested at the indicated time-points.
      Immunohistochemical (IHC) and Western Blot analyses were performed to detect the
      expression level of alpha-smooth muscle actin (alpha-SMA) in the scar tissue. The
      scars shrunk and the volumes reduced at 3 to 4 weeks after surgery; however, at 5
      weeks postsurgery, the volumes increased. IHC and Western blot analyses indicated
      the expression of alpha-SMA was significantly enhanced 3 to 4 weeks, but reduced
      in the 5 weeks after surgery. Overall, the degree of scar hyperplasia after cleft
      lip surgery in rabbits was normally distributed and the scarring was most severe
      in the 3 to 4 weeks after cleft lip surgery. The study confirms a novel animal
      model for the assessment of therapies for the treatment of scar hyperplasia of
      human cleft lip in future.

PMID- 29381622
TI  - Nasal Columellar Reconstruction With Reverse Lateral Nasal Artery Pedicled
      Nasolabial Island Flap.
AB  - Nasal columellar is a complex area to reconstruct due to its unique esthetic and
      functional characteristics. Malignancy, trauma, infection, and esthetic surgery
      complications can cause columellar defect. Among many surgical plans, nasolabial
      island flap is most commonly used. However, flap congestions occasionally occur
      which inevitably lead to leech therapy. The authors introduce reverse lateral
      nasal artery pedicled nasolabial island flap, which has lower risk of
      postoperative complications.

PMID- 29381623
TI  - Giant Parapharyngeal Space Lipoma Extending to the Pterygoid Region (Anterior
      Skull Base).
AB  - Although lipoma is frequently seen in the head and neck region, but occurrence of
      the lipoma in the parapharyngeal space is rare. It is extremely rare for a
      parapharyngeal lipoma to extent to the pterygoid region (ie, anterior skull
      base). Management of giant parapharyngeal space lipoma with skull base extension
      and proximity to the vital neurovascular structures poses a challenge to surgeon.
      The authors report a patient with giant lipoma extending from the upper border of
      the clavicle to the pterygoid region. Complete excision was done using upper
      transverse cervical incision and pterygoid region was approached after removal of
      the ipsilateral submandibular gland. Surgery produced excellent cosmetic results
      with no functional impairment.

PMID- 29381624
TI  - Usefulness of Early Plate Removal in Patients With Occlusal Discrepancies After
      Sagittal Split Ramus Osteotomy.
AB  - The aim of this study was to evaluate the effects of early removal of fixed
      plates in patients with occlusal discrepancies after sagittal split ramus
      osteotomy (SSRO) with a focus on the positional relationship of the
      temporomandibular joint (TMJ). Sagittal split ramus osteotomy with/without Le
      Fort I osteotomy was performed on 98 patients with mandibular prognathism. Of
      these 98 patients, 15 with occlusal discrepancies and/or TMJ symptoms underwent
      early plate removal after SSRO. Finally, 12 consecutive patients were evaluated
      in this study: 7 underwent bilateral SSRO, 1 underwent unilateral SSRO, and 4
      underwent bilateral SSRO with maxillary advancement. The axiolateral TMJ Schuller
      method was used to evaluate the TMJ position. The authors measured 3 spaces
      (anterior, superior, and posterior joint spaces) between the condyle and glenoid
      fossa in the sagittal plane. The anterior and superior joint spaces were
      significantly larger immediately after the operation than before the operation.
      After early plate removal, these spaces significantly decreased in size. The
      posterior joint space increased, but with no significant difference. Three months
      after SSRO, the size of each of the 3 spaces was closely related to its
      preoperative size. In conclusion, these results suggest that early removal of
      fixed plates is 1 treatment option for postoperative occlusal discrepancies after
      SSRO.

PMID- 29381625
TI  - Radiological Analysis of Orbital Cavernous Hemangiomas: A Review and Comparison
      Between Computed Tomography and Magnetic Resonance Imaging.
AB  - Cavernous hemangiomas are the most common benign orbital tumors in the orbit, but
      radiological differentiation from other solitary orbital masses can still be
      challenging at times. While there have been previous studies describing the
      radiological characteristics of cavernous hemangiomas on computed tomography (CT)
      and magnetic resonance imaging (MRI), there have not been any studies comparing
      the 2 imaging modalities. The purpose of our study was to evaluate CT and MRI
      findings of orbital cavernous hemangiomas and compare both modalities.We
      performed a cross-sectional study of patients with a histopathological diagnosis
      of cavernous hemangioma over a 20-year period from January 1997 to December 2016
      in a single tertiary institution.Our study included 77 patients; mean age was
      46.6 +/- 11.2 years, and females comprised 68.8%. The lateral orbit (23.4%) was
      the most common location. The masses were well-defined, with 55.8% being ovoid,
      27.3% round, and 16.9% lobulated. The most common enhancement pattern on CT was a
      small point starting in the periphery, progressing to heterogeneous filling in
      the late phase. The most common enhancement pattern on MRI was multiple patchy
      starting points, widespread across the tumor, with a final homogeneous filling in
      the late phase.Significant differences between CT and MRI were found in terms of
      area, location, and number of starting points of contrast enhancement in the
      early phase. We also found that the use of MRI is limited in differentiating fast
      filling cavernous hemangiomas from other orbital tumors and in such cases,
      contrast-enhanced CT would be helpful.

PMID- 29381626
TI  - The Measurement of Various Anatomical Structures and Assessment of Morphometric
      Development of Fetal Skull Base.
AB  - BACKGROUND: As the skull base has a complex anatomy, we underline the importance
      of anomalies for side asymmetry. It is useful to investigate relationship between
      anatomical structures for the surgical procedure orientations. Dural adherence,
      enlarged superior petrosal sinus, influence of neural crest cells, and cranial
      base ossification are among the factors in morphometric growth on skull base.
      MATERIAL AND METHODS: Twenty-five fetuses of an estimated gestational age ranging
      from 17 to 34 weeks were studied in the Anatomy Laboratory of Mersin University
      Medical Faculty. Craniotomy was made to each fetus and brain hemispheres were
      dissected. We put plates, passing from the external points of lateral and
      anterior-posterior borders of fetus heads that are perpendicular to each other.
      An analytical calculation was formulated for the angle of foraminae to the root
      of zygoma by using different formulations depending on their posterior or
      anterior location to the root of zygoma. Statistical method was based on
      correlation analysis, simple regression, independent 2 group t tests, SPSS20.0,
      and MedCalc 11.5 (MedicReS, New York, NY). RESULTS: Neither side dominance for
      the jugular foramen, nor the differences of foramen rotundum, spinosum, and ovale
      to anterior skull wall, root of zygoma, and to midline were found to be
      significant. CONCLUSION: There is a debate on asymmetry of foramina of the skull
      base. No certain consensus about the initiation time and the causes of asymmetry
      in the past was documented. Studies are to be encouraged to further enlighten pre
      postnatal factors affecting the fetal skull base morphometrism.

PMID- 29381627
TI  - A New Technique in Surgical Management of the Giant Cerebral Hydatid Cysts.
AB  - OBJECTIVES: In hydatid disease, the central nervous system is affected
      approximately in 2% to 3% of patients. Surgical management in these patients is
      important. To develop a surgical technique to avoid the formation of great volume
      of cavity after hydatid cyst removal and prevent complications associated with
      brain collapse and cortical convolution. PATIENTS AND METHODS: In 2 patients,
      hydatid cysts were delivered by this new technique. A balloon filled with 150 cc
      of sterile air/distilled water was placed in the cavity until the balloon filled
      the entire cavity. Air/distilled water evacuation was continued at a rate of 20
      cc/d and, after a week, eventually, the balloons were removed RESULTS:: All cysts
      were delivered without rupture. Neurologic outcomes were good. No complications
      were observed related to usage of the system such as balloon rupture, evacuation
      problems, and infection. CONCLUSION: The authors believe that the balloon
      insertion technique may be a useful method to prevent brain collapse, cortical
      convolution, and complications associated with this condition. Further technical
      refinements of the system are needed for better results.

PMID- 29381628
TI  - Quality of Postoperative Pain Management After Maxillofacial Fracture Repair.
AB  - BACKGROUND: Effective pain management is an essential component in the
      perioperative care of surgical patients. However, postoperative pain after
      maxillofacial fracture repair and its optimal therapy has not been described in
      detail. MATERIALS AND METHODS: In a prospective cohort study, 95 adults rated
      their pain on the first postoperative day after maxillofacial fracture repair
      using the questionnaire of the Quality Improvement in Postoperative Pain
      Management (QUIPS) project. Quality Improvement in Postoperative Pain Management
      allowed for a standardized assessment of patients' characteristics and pain
      related parameters. RESULTS: Overall, the mean maximal pain and pain on activity
      (numeric rating scales) were significantly higher in patients with mandibular
      fractures than in patients with midface fractures (P = 0.002 and P = 0.045,
      respectively). In patients with mandibular fractures, a longer duration of
      surgery was significantly associated with higher satisfaction with pain intensity
      (P = 0.015), but was more frequently associated with postoperative vomiting (P =
      0.023). A shorter duration of surgery and an absence of preoperative pain
      counseling in these patients were significantly correlated to desire for more
      pain medication (P = 0.049 and P = 0.004, respectively). Patients with mandibular
      fractures that received opioids in the recovery room had significantly higher
      strain-related pain (P = 0.017). In patients with midface fractures, a longer
      duration of surgery showed significantly higher levels of decreased mobility (P =
      0.003). Patients receiving midazolam for premedication had significantly less
      minimal pain (P = 0.021). CONCLUSIONS: Patients with mandibular fractures seem to
      have more postoperative pain than patients with midface fractures. Monitoring of
      postsurgical pain and a procedure-specific pain-treatment protocol should be
      performed in clinical routine.

PMID- 29381629
TI  - Intraoral Prosthetic Chin Augmentation With Vertical Incisions.
AB  - To explore a new surgical approach for chin augmentation using a prosthesis with
      3 intraoral vertical incisions whereby placement of the prosthesis is more
      convenient and accurate, with fewer postoperative complications. Following the
      anatomic characteristics of the chin, a bilateral mucosal vertical incision and a
      median observation incision are made. The V-shaped mark on the upper side of the
      prosthesis can be seen through the observation incision after it is placed from
      the lateral incision into the predesigned compartment. The incision can be
      sutured if there is no bleeding in the operation area. Surgery performed in all
      19 patients with mild microgenia with 6 to 12 months of follow-up resulted in
      satisfactory chin and face shape without any complications. The application of
      this novel method can correct McCarthy type I microgenia with more accurate
      positioning, less possibility of bilateral sideways and/or up/down movement, and
      fewer complications.

PMID- 29381630
TI  - The Infraorbital Foramen Is Located Midway Between the Nasospinale and Jugale:
      Considerations for Infraorbital Nerve Block and Maxillofacial Surgery.
AB  - Identification of the infraorbital foramen is important in infraorbital nerve
      block and the prevention of iatrogenic injury of the infraorbital nerve in
      maxillofacial surgeries. This study assessed the location of 887 infraorbital
      foramina from 518 adult crania of varied sex and population. The study assessed
      the midpoint of a line segment spanning from nasospinale to jugale (NS-J)
      relative to the infraorbital foramen. The mean distance of the NS-J midpoint from
      the infraorbital foramen was 2.1 +/- 1.9 mm (mean +/- SD) with a mode of 0 mm
      (266:887; 30%). The NS-J midpoint was located in the same plane or inferior to
      the infraorbital foramen in 98.4% of sides (873:887). There were no significant
      differences between sexes, populations, or sides with regard to the NS-J midpoint
      to infraorbital foramen distance. The NS-J midpoint can be used to locate the
      infraorbital foramen in both females and males of varied populations regardless
      of craniofacial diversity. The results of this study will aid in infraorbital
      nerve block procedures and maxillofacial surgery.

PMID- 29381631
TI  - Effects of Platelet-Rich Fibrin Membrane on Sciatic Nerve Regeneration.
AB  - Alternative treatment approaches to improve the regeneration capacity of damaged
      peripheral nerves are currently under investigation. The objective of the present
      study was to evaluate the effects of platelet-rich fibrin (PRF) membrane after
      sciatic nerve crush injury in rabbits by histomorphometric and electromyographic
      analysis. The left sciatic nerves of 20 male Vienna rabbits were clamped for 30
      seconds to induce crush injuries. Animals were randomly divided into 2 groups:
      PRF and control. For each animal in the PRF group, a PRF membrane was wrapped
      around the injured part of the sciatic nerve to form a tube. No additional
      treatment was performed in the control group. After a 12-week healing period,
      tissue samples from the injured nerve region were harvested and the g-ratio of
      axons, axon density, and impulse transmission changes were evaluated. Analysis
      revealed that axon density differences were not statistically significant between
      groups (P = 0.139). The rate of nerve fibers with optimum g-ratio was
      significantly lower in the PRF group than in the control group (P = 0.02).
      Conduction velocity differences between groups were not statistically
      significant. Although PRF application has previously shown positive regeneration
      effects on maxillofacial tissues, local PRF membrane application in tube form did
      not show any histomorphometric or functional improvement in peripheral nerve
      crush injury recovery.

PMID- 29381632
TI  - Reliability of the Dutch Cleft Speech Evaluation Test and Conversion to the
      Proposed Universal Scale.
AB  - The Dutch cleft speech evaluation test (DCSET) has been implemented by the speech
      language pathologists nationwide in the Netherlands since 2003, but the inter-
      and intrarater reliability was unknown. Two speech-language pathologists
      experienced in evaluating cleft speech assessed audio recordings of 20 children
      with cleft speech using the DCSET, and reassessed the recordings 2 weeks later.
      Intra- and interrater reliability was calculated, but found to be unacceptable
      after the first phase of this study using audio recordings. Following consensus
      training and some modifications in the scoring scales, the study was repeated
      using video recordings of 20 different children with cleft speech. Results from
      the second phase of this study using standardized video recordings showed fair,
      moderate, and good reliability on different subsets of the DCSET. Intrarater
      reliability (Kappa 0.59-1.00) was greater than interrater reliability (Kappa 0.33
      0.79). Interrater reliability agreement was good (Kappa 0.63-0.79) for consonant
      production errors and speech understandability and acceptability, moderate (Kappa
      0.59) for the resonance of the nasal passage, and fair (Kappa 0.33-0.37) for the
      resonance of the mixed and denasal passages. Subsequently, an algorithm was made
      to convert the DCSET scales to universal scales for international comparison of
      cleft speech as suggested by Henningsson et al in 2008.

PMID- 29381633
TI  - Evaluation of the Effect of Topical Application of Nigella sativa on Acute
      Radiation-Induced Nasal Mucositis.
AB  - The goal of this study was to demonstrate the effect of radiotherapy (RT) on
      nasal mucosa in rats and to evaluate the radioprotective effects of the topical
      application of black seed oil (Nigella sativa [NS]) to treat acute radiation
      induced nasal mucositis.A total of 18 rats were randomized into 3 groups, with 6
      animals per group. The rats in group 1 were topically administered saline in the
      nasal cavity after sham irradiation. Group 2 received saline at the same dose
      after irradiation. Group 3 was given NS after irradiation. The rats in groups 2
      and 3 were irradiated with a single dose of 40 Gy to the nasal and paranasal
      area. Only one drop of saline (0.05 mL) was applied to each nostril in the first,
      second, and third days after RT in groups 1 and 2. One drop of cold press NS
      (0.05 mL) was applied to each nostril in group 3. Fourteen days after
      irradiation, the nasal mucosal tissues were excised for histopathological
      evaluation. Vascular dilatation, inflammatory cell infiltration, superficial
      erosion, and formation of exudates were classified according to the severity.No
      evidence of mucositis was observed in group 1. Of all the parameters the only
      statistically significant difference between groups 2 and 3 were observed for
      "superficial erosion' (P < 0.05). Overall microscopic observations in the NS
      treated group were better than in group 2.The preliminary results of our study
      have shown that local application of NS to the nasal mucosa may be an effective
      treatment of acute nasal mucositis due to RT.

PMID- 29381634
TI  - The Sellar Tumor: Metastasis or Chordoma?
AB  - Chordomas are uncommon, locally invasive chordate tumors, which are mostly
      observed in the axial skeleton. Numerous papers have described similar patients
      around different anatomic locations; however, rare document previously reported
      that intracranial chordoma was associated with clear cell renal cell carcinoma
      (ccRCC). The authors report a 51-year-old male patient with a history of right
      radical nephrectomy for ccRCC presented to us with progressive blurred vision.
      Ophthalmic examination showed vision loss and visual field defects. Magnetic
      resonance imaging demonstrated pituitary tumor with hemorrhage, which was
      compressing the optic chiasm. He underwent a transnasal endoscope resection of
      the sellar mass. The immediate postoperative pathologic result was simply
      considered to be pituitary metastasis from ccRCC. After further
      immunohistochemical study, pathology diagnosis was made the necessary corrections
      to be the sellar chordoma. The authors summarize this exceptional patient and
      review the pertinent literature briefly.

PMID- 29381635
TI  - Subdural Abnormal Communicating Vessel in Chronic Subdural Hematoma.
AB  - Traditionally, lacerations of bridging vessels were surmised to cause chronic
      subdural hematoma (CSDH), although neither observation studies nor medical
      research was able to testify this. Nowadays, an inflammatory process is known to
      take place in the development of CSDH. Of note, post-traumatic angiogenesis at
      its early stage also features inflammation with immune cell infiltration. The
      authors found a patient suffering from CSDH with unusual angiogenesis between
      dura and pia matters. The observation of dura-and-pia angiogenesis may be a piece
      of evidence to underline compensatory reaction of central nervous system to
      offset the negative effects produced by CSDH, and points out to a possible
      approach of bolstering angiogenesis to manage ischemic diseases in cerebral
      hemispheres.

PMID- 29381636
TI  - The Distal Stump of the Intramuscular Motor Branch of the Obturator Nerve Is
      Useful for the Reconstruction of Long-Standing Facial Paralysis Using a Double
      Powered Free Gracilis Muscle Flap Transfer.
AB  - BACKGROUND: Double innervation of the transferred muscle with the contralateral
      facial nerve and the ipsilateral masseteric nerve has recently been reported by
      some authors. The aim of this study was to assess the utility of our procedure of
      double innervation of free gracilis muscle for reconstruction of long-standing
      facial palsy. PATIENTS AND METHODS: In our department, 6 cases of long-standing
      facial paralysis (4 cases of complete palsy and 2 of incomplete palsy) were
      reconstructed using a free gracilis muscle double innervated with the masseteric
      and contralateral facial nerves. The patient age ranged from 37 to 79 years
      (average 56.7 +/- 15.7). In our procedure, the intramuscular motor branch of the
      transferred muscle was identified and sutured to the ipsilateral masseteric nerve
      in an end-to-end fashion, and the obturator nerve of the transferred muscle was
      sutured to the cross-facial nerve graft, which was coapted with the contralateral
      facial nerve by end-to-end suturing. RESULTS: All patients were followed up for
      >18 months and recovered their smiling function. The voluntary movement of the
      transferred muscle with teeth clenching was observed at approximately 4.7 months,
      and this movement combined with contralateral mouth angle elevation was observed
      at approximately 9.5 months after the surgery. CONCLUSIONS: Our experience
      suggests that the distal stump of the intramuscular motor branch of the obturator
      nerve may be useful for facial reanimation via double-powered free gracilis
      muscle flap transfer.

PMID- 29381637
TI  - Eyebrow Position and Shape Favored by Korean Women.
AB  - PURPOSE: The shape and position of the eyebrows are among the most important
      facial features from an esthetic point of view. However, significant cultural
      differences exist with respect to the eyebrow shape and position that are
      considered ideal. The purpose of this study was to identify the position and
      shape of eyebrows preferred by Korean women and to apply these, including
      forehead lifts, to the clinics. METHODS: The authors took full facial photographs
      in the Frankfort plane of Korean women aging from young childhood to their 50s.
      On the basis of these, 2 parameters were calculated: first, the height-to-width
      ratio (HWR), the ratio between the vertical distance from the brow apex to the
      palpebral fissure and the horizontal distance from the medial canthus to the
      lateral canthus; and second, the takeoff angle (TOA), the angle between the
      straight line connecting the 2 lateral canthi and the line from the brow apex
      through the center of the medial brow segment. The authors then had drawings of
      "Anastasia arch" eyebrows made; as high eyebrows are considered beautiful in
      Korea, and the eyebrows of women in their 20s were the highest, the drawings
      depicted the mean HWR and TOA values for this age group and their various degrees
      of deviation. These drawings were shown to 300 women aged 21 to 40 years from May
      1 to June 30, 2014; they were instructed to choose the drawing they preferred
      among the 5 drawings differing in HWR and again among the 5 differing in TOA.
      RESULTS: Among the 99 Korean women in their 20s, the mean HWR and TOA was 1:1.01
      +/- 0.23 and 12 degrees  +/- 5.2 degrees , respectively. Regarding the survey,
      the most preferred HWR was 1:1.0, which was selected by 204 respondents (68%);
      the most preferred TOA was 10 degrees , which was chosen by 122 respondents
      (40.7%). CONCLUSION: This study shows that HWR gradually decreases and TOA
      increases with age. Furthermore, Korean women's preferred eyebrows have an HWR of
      ~1:1 and a TOA of ~10 degrees . These results could guide plastic surgeons
      performing periorbital rejuvenation surgeries, including brow lifts, not only for
      Koreans but also for North-East Asians.

PMID- 29381638
TI  - Unilateral Isolated Hypoglossal Nerve Palsy Caused by Gunshot Injury.
AB  - Cranial nerve palsies after gunshot injury are not uncommon. However, in the
      literature, only 1 patient with isolated hypoglossal nerve paralysis caused by
      gunshot has been published. The authors describe a 34-year-old man suffering from
      unilateral isolated hypoglossal nerve palsy caused by gunshot injury as a second
      reported patient. The bullet entered maxillary sinus, and caused condylar
      fracture, then ended up C1-2 interspace. The bullet was surgically removed by a
      posterior approach. It is important to pay attention to hypoglossal nerve injury
      when confronted with a gunshot wound. The authors recommend early and sufficient
      surgical decompression.

PMID- 29381639
TI  - Condylar Hyperplasia in a Monozygotic Twin Girl: An Argument About Etiology.
AB  - The diagnosis of unilateral condylar hyperplasia (UCH) requires a combined
      assessment consisting of clinical, radiological, and histopathological
      examination. The etiology of this condition is unknown. The purpose of this study
      is to report a rare case of UCH in a monozygotic twin. A 15-year-old girl was
      referred to our department complaining of facial asymmetry and malocclusion.
      Computed tomography and single-photon emission computed tomography imaging reveal
      enlargement of the left condyle and condylar neck, and an increased uptake that
      was diagnosed as active UCH. During the investigation of family and co-twin
      facial profile, no cases of UCH were identified. From the case reported in this
      study, the authors raise a hypothesis that can exist some environmental factor
      that is related in the development of condylar hyperplasia given the occurrence
      of this disease in one of twins.

PMID- 29381640
TI  - Management of Temporomandibular Joint Ankylosis With Dentofacial Deformities in
      Children.
AB  - This retrospective study described the authors' experience in the treatment of
      temporomandibular joint (TMJ) ankylosis with dentofacial deformities in 18
      pediatric patients during a 4-year period. These patients underwent different
      types of arthroplasty with condylar reconstruction, simultaneously with treatment
      of dentofacial deformities. Re-ankylosis was confirmed if maximal incisal opening
      (MIO) was <20 mm. Clinical outcomes were evaluated in terms of oral function,
      radiography, and medical photography. Patients were followed up for a mean time
      of 24.8 months. No infections, re-ankylosis, or permanent facial nerve damage
      were found during the hospitalization or follow-up period. All patients achieved
      significant improvements in MIO and oral function. The dentofacial deformities in
      most patients were improved to varying degrees. The results provided more useful
      information for the management of the pediatric patients with TMJ ankylosis and
      secondary dentofacial deformities. Early treatment and close follow-up play an
      important role in the management of these patients.

PMID- 29381641
TI  - Effects of Nasoalveolar Molding Therapy on Alveolar and Palatal Cleft Deformities
      in Unilateral and Bilateral Cleft Lip and Palate.
AB  - OBJECTIVE: The purpose of this study was to evaluate and compare the efficacy of
      nasoalveolar molding (NAM) therapy in the improvement of alveolar and palatal
      cleft deformity on unilateral (UCLP) versus bilateral (BCLP) cleft lip and
      palate. MATERIALS AND METHODS: A total of 19 UCLP (14 boys and 5 girls) and 8
      BCLP (7 boys and 1 girl) infants completed NAM therapy were included in this
      study. Standardized parameters of cleft width of alveol and palate were measured
      on photocopies taken from the pre- and post-treatment plaster casts. To assess
      the intragroup differences, paired-samples test in UCLP and Wilcoxon test in BCLP
      groups were used. Mann-Whitney U test was used to evaluate the differences
      between the groups. RESULTS: Significant decreases in alveolar and palatal cleft
      gaps were achieved in an average period of 3.3 +/- 1.9 and 3.7 +/- 1.6 months in
      UCLP and BCLP patients, respectively. The alveolar cleft decreased 7.85 +/- 4.59
      mm in UCLP and 4.25 +/- 3.13 and 3.81 +/- 3.50 mm in right and left alveolar
      cleft sides in BCLP, respectively. The palatal clefts were decreased 4.63 +/-
      2.44 mm in medial and 3.72 +/- 2.62 mm in posterior parts in UCLP. The decrements
      in BCLP were 3.00 +/- 2.75 mm in medial and 2.88 +/- 2.75 mm in posterior palatal
      cleft distances. No significant differences were determined in the amount of
      alveolar or palatal cleft closure between UCLP and BCLP groups. The only decrease
      in arch width was 1.39 mm in medial part of palate in UCLP. CONCLUSION: The NAM
      device provides significant decreases in both alveolar and palatal cleft
      deformities in UCLP and BCLP infants, as compared with their birth status.

PMID- 29381642
TI  - The First Patient Report of Tongue Abscess Among Iraqi Population.
AB  - Tongue abscess is a serious clinical entity which scarcely affects the tongue. It
      should be treated urgently to prevent airway obstruction or dissemination of
      infection to a more deep or distant area of the body. This article presented the
      first clinical report of tongue abscess in Iraq which discussed its clinical
      presentation, diagnosis, and treatment with a review of literature.

PMID- 29381643
TI  - Uvula Abscess in a Newborn Infant.
AB  - Abscesses can be found in several places in the oral cavity, most commonly
      occurring in peritonsillar and periodontal regions. In this report, the authors
      described a uvula abscess in a 1-month-old term newborn who was brought to the
      pediatric outpatient clinic with the complaints of difficulty in sucking
      swallowing and refusal to suck at the breast. To the best of the authors'
      knowledge this is the first report of a uvula abscess in the literature.

PMID- 29381644
TI  - Schwannoma of the Membranous Nasal Septum: a Clinical Report With Aesthetic
      Approach.
AB  - Schwannoma is an uncommon tumor of nerve sheath that arises from any peripheral,
      cranial, or autonomic nerve. Only 4% of head and neck schwannomas originate from
      the sinonasal tract, and a finding of a schwannoma in the nasal septum is
      exceedingly rare. The authors experienced nasal septal schwannoma with the
      functional and aesthetic consideration of nasal contour. The authors present an
      open rhinoplasty approach for nasal septal schwannoma which has not been reported
      in the previous literature yet.

PMID- 29381645
TI  - PVR/CD155 Ala67Thr Mutation and Cleft Lip/Palate.
AB  - The 19q13 locus has been linked to cleft lip and palate by our group and
      independently by others. Here we fine mapped the region in an attempt to identify
      an etiological variant that can explain cleft lip and palate occurrence. A total
      of 2739 individuals born with cleft lip and palate, related to individuals born
      with cleft lip and palate, and unrelated were studied. We used linkage and
      association approaches to fine map the interval between D19S714 and D19S433 and
      genotypes were defined by the use of TaqMan chemistry. We confirmed our previous
      findings that markers in PVR/CD155 are associated with cleft lip and palate. We
      studied the mutation Ala67Thr further and calculated its penetrance. We also
      attempted to detect PVR/CD155 expression in human whole saliva. Our results
      showed that markers in PVR/CD155 are associated with cleft lip and palate and the
      penetrance of the Ala67Thr is very low (between 1% and 5%). We could not detect
      PVR/CD155 expression in adult human whole saliva and PVR/CD155 possibly interacts
      with maternal infection to predispose children to cleft lip only.

PMID- 29381648
TI  - Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From
      GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs: Erratum.

PMID- 29381649
TI  - Video-Recorded Validation of Wearable Step Counters under Free-living Conditions.
AB  - PURPOSE: The purpose of this study was to determine the accuracy of 14-step
      counting methods under free-living conditions. METHODS: Twelve adults (mean +/-
      SD age, 35 +/- 13 yr) wore a chest harness that held a GoPro camera pointed down
      at the feet during all waking hours for 1 d. The GoPro continuously recorded
      video of all steps taken throughout the day. Simultaneously, participants wore
      two StepWatch (SW) devices on each ankle (all programmed with different
      settings), one activPAL on each thigh, four devices at the waist (Fitbit Zip,
      Yamax Digi-Walker SW-200, New Lifestyles NL-2000, and ActiGraph GT9X (AG)), and
      two devices on the dominant and nondominant wrists (Fitbit Charge and AG). The
      GoPro videos were downloaded to a computer and researchers counted steps using a
      hand tally device, which served as the criterion method. RESULTS: The SW devices
      recorded between 95.3% and 102.8% of actual steps taken throughout the day (P >
      0.05). Eleven step counting methods estimated less than 100% of actual steps;
      Fitbit Zip, Yamax Digi-Walker SW-200, and AG with the moving average vector
      magnitude algorithm on both wrists recorded 71% to 91% of steps (P > 0.05),
      whereas the activPAL, New Lifestyles NL-2000, and AG (without low-frequency
      extension (no-LFE), moving average vector magnitude) worn on the hip, and Fitbit
      Charge recorded 69% to 84% of steps (P < 0.05). Five methods estimated more than
      100% of actual steps; AG (no-LFE) on both wrists recorded 109% to 122% of steps
      (P > 0.05), whereas the AG (LFE) on both wrists and the hip recorded 128% to 220%
      of steps (P < 0.05). CONCLUSIONS: Across all waking hours of 1 d, step counts
      differ between devices. The SW, regardless of settings, was the most accurate
      method of counting steps.

PMID- 29381647
TI  - Recommendations for Management of Endemic Diseases and Travel Medicine in Solid
      Organ Transplant Recipients and Donors: Latin America.
AB  - The Recommendations for Management of Endemic Diseases and Travel Medicine in
      Solid-Organ Transplant Recipients and Donors: Latin America clinical practice
      guideline is intended to guide clinicians caring for solid-organ transplant (SOT)
      donors, candidates and recipients regarding infectious diseases (ID) issues
      related to this geographical region, mostly located in the tropics. These
      recommendations are based on both systematic reviews of relevant literature and
      expert opinion from both transplant ID and travel medicine specialists. The
      guidelines provide recommendations for risk evaluation and laboratory
      investigation, as well as management and prevention of infection of the most
      relevant endemic diseases of Latin America. This summary includes a brief
      description of the guideline recommendations but does not include the complete
      rationale and references for each recommendation, which is available in the
      online version of the article, published in this journal as a supplement. The
      supplement contains 10 reviews referring to endemic or travel diseases (eg,
      tuberculosis, Chagas disease [ChD], leishmaniasis, malaria, strongyloidiasis and
      schistosomiasis, travelers diarrhea, arboviruses, endemic fungal infections,
      viral hepatitis, and vaccines) and an illustrative section with maps
      (http://www.pmourao.com/map/). Contributors included experts from 13 countries
      (Brazil, Canada, Chile, Denmark, France, Italy, Peru, Spain, Switzerland, Turkey,
      United Kingdom, United States, and Uruguay) representing four continents (Asia,
      the Americas and Europe), along with scientific and medical societies.

PMID- 29381650
TI  - Effects of Different Exercise Modes on Arterial Stiffness and Nitric Oxide
      Synthesis.
AB  - PURPOSE: Aerobic training (AT) and high-intensity intermittent training (HIIT)
      reduce arterial stiffness, whereas resistance training (RT) induces deterioration
      of or no change in arterial stiffness. However, the molecular mechanism of these
      effects of different exercise modes remains unclear. This study aimed to clarify
      the difference of different exercise effects on endothelial nitric oxide synthase
      (eNOS) signaling pathway and arterial stiffness in rats and humans. METHODS: In
      the animal study, forty 10-wk-old male Sprague-Dawley rats were randomly divided
      into four groups: sedentary control (CON), AT (treadmill running, 60 min at 30
      m.min, 5 d.wk for 8 wk), RT (ladder climbing, 8-10 sets per day, 3 d.wk for 8
      wk), and HIIT (14 repeats of 20-s swimming session with 10-s pause between
      sessions, 4 d.wk for 6 wk from 12-wk-old) groups (n = 10 in each group). In the
      human study, we confirmed the effects of 6-wk HIIT and 8-wk AT interventions on
      central arterial stiffness and plasma nitrite/nitrate level in untrained healthy
      young men in randomized controlled trial (HIIT, AT, and CON; n = 7 in each
      group). RESULTS: In the animal study, the effect on aortic pulse wave velocity
      (PWV), as an index of central arterial stiffness, after HIIT was the same as the
      decrease in aortic PWV and increase in arterial eNOS/Akt phosphorylation after
      AT, which was not changed by RT. A negative correlation between aortic PWV and
      eNOS phosphorylation was observed (r = -0.38, P < 0.05). In the human study, HIIT
      and AT-induced changes in carotid-femoral PWV (HIIT -115.3 +/- 63.4 and AT 
      157.7 +/- 45.7 vs CON 71.3 +/- 61.1 m.s, each P < 0.05) decreased, and plasma
      nitrite/nitrate level increased compared with those in CON. CONCLUSIONS: HIIT may
      reduce central arterial stiffness via the increase in aortic nitric oxide
      bioavailability despite it being done in a short time and short term and has the
      same effects as AT.

PMID- 29381651
TI  - Exercise Effects on Adipose Tissue Postprandial Lipolysis and Blood Flow in
      Children.
AB  - : Poor suppression of lipolysis and blunted increase in blood flow after meal
      ingestion in obese adults may indicate resistance to the antilipolytic action of
      insulin. Exercise may be used to normalize lipolytic responses to food intake by
      increasing insulin sensitivity. PURPOSE: To determine if acute bouts of aerobic
      exercise and/or excise training alter lipolytic and blood flow responses to food
      intake in lean (LN) and obese (OB) children. METHODS: Sixty-five children (9-11
      yr) were randomized into acute exercise (EX: 16 LN and 28 OB) or control (CON: 9
      LN and 12 OB) groups that exercised (EX), or rested (CON) between standardized
      breakfast and lunch. Microdialysis probes were inserted into the subcutaneous
      abdominal adipose tissue to monitor interstitial glycerol (lipolysis) and blood
      flow. Changes in interstitial glycerol and nutritive flow were calculated from
      dialysate samples before and after each meal. A subgroup (OB = 15 and LN = 9)
      from the acute exercise group underwent 16 wk of aerobic exercise training.
      RESULTS: Poor suppression of lipolysis and a blunted increase in adipose tissue
      nutritive blood flow in response to breakfast was associated with BMI percentile
      (r = 0.3, P < 0.05). These responses were normalized at lunch in the OB in the EX
      (P < 0.05), but not in OB in the CON. Sixteen weeks of exercise training did not
      improve meal-induced blood flow and marginally altered the antilipolytic response
      to the two meals (P = 0.06). CONCLUSIONS: Daily bouts of acute aerobic exercise
      should be used to improve the antilipolytic and nutritive blood flow response to
      a subsequent meal in obese children.

PMID- 29381652
TI  - Comparison of Two Generations of ActiGraph Accelerometers: The CARDIA Study.
AB  - PURPOSE: This study aimed to examine the comparability of the ActiGraph 7164 and
      wGT3X-BT wear time, count-based estimates, and average time per day in physical
      activity of different intensities. METHODS: We studied 87 Coronary Artery Risk
      Development in Young Adults (CARDIA) participants 48-60 yr of age who
      simultaneously wore the 7164 and wGT3X-BT accelerometers at the waist in 2015
      2016, with wear time of >=4 of 7 d, >=10 h.d for both monitors. Freedson
      cutpoints (counts per minute) were used to define sedentary (<100), light (100
      1951), moderate (1952-5724), and vigorous activity (>=5725). Agreement was
      evaluated using paired-difference tests, intraclass correlation coefficients, and
      Bland-Altman plots. Given systematic differences in count-based estimates between
      monitors, a calibration formula applied to the wGT3X-BT values was obtained by
      linear regression. RESULTS: Total detected wear time minutes per day was nearly
      identical between the 7164 and the wGT3X-BT (881.5 +/- 70.9 vs 880.3 +/- 78.1, P
      = 0.72). The wGT3X-BT values were calibrated to the 7164 values by dividing
      counts by 1.088. After calibration, no differences were observed between the 7164
      and the wGT3X-BT in total counts per day (310,184 +/- 129,189 vs 307,085 +/-
      135,362, P = 0.48), average counts per min per day (349.5 +/- 139.5 vs 346.5 +/-
      147.2, P = 0.54), sedentary (513.2 +/- 93.6 vs 509.6 +/- 98.6, P = 0.23), light
      (335.3 +/- 81.5 vs 338.7 +/- 81.1, P = 0.22), moderate (31.0 +/- 21.9 vs 30.3 +/-
      23.4, P = 0.31), or moderate-to-vigorous minutes per day (33.1 +/- 24.6 vs 32.0
      +/- 26.0, P = 0.13). A significant difference was observed for vigorous minutes
      per day (0.2 +/- 1.0 vs 0.0 +/- 0.3, P < 0.01); however, the absolute difference
      was marginal. Intraclass correlation coefficients showed excellent agreement for
      all measures (0.95-0.99). CONCLUSIONS: After applying a calibration formula, the
      7164 and wGT3X-BT were comparable for total wear time, count-based estimates, and
      average minutes per day in sedentary, light, moderate, and moderate-to-vigorous
      activity. Findings illustrate a novel methodological approach to facilitate
      accelerometer data harmonization.

PMID- 29381653
TI  - Spinal manipulative therapy reduces peripheral neuropathic pain in the rat.
AB  - Spinal manipulative therapy, including low-velocity variable-amplitude spinal
      manipulation (LVVA-SM), relieves chronic low back pain, especially in patients
      with neuropathic radiating leg pain following peripheral nervous system insult.
      Understanding the underlying analgesic mechanisms requires animal models. The aim
      of the current study was to develop an animal model for the analgesic actions of
      LVVA-SM in the setting of peripheral neuropathic pain. Adult male Sprague-Dawley
      rat sciatic nerve tibial and common peroneal branches were transected, sparing
      the sural branch (spared nerve injury, SNI). After 15-18 days, rats were assigned
      randomly to one of three groups (n=9 each group): LVVA-SM at 0.15-or 0.16-Hz or
      Control. LVVA-SM (20 degrees  flexion at the L5 vertebra with an innovative
      motorized treatment table) was administered in anesthetized rats for 10 min.
      Control rats were administered anesthesia and positioned on the treatment table.
      After 10, 25, and 40 min, the plantar skin of the hindpaw ipsilateral to SNI was
      tested for mechanical sensitivity (paw withdrawal threshold to a logarithmic
      series of Semmes-Weinstein monofilaments) and cold sensitivity (duration of paw
      lifting, shaking, and/or licking to topical acetone application). SNI produced
      behavioral signs of mechanical and cold allodynia. LVVA-SM reduced mechanical,
      but not cold, hypersensitivity compared with Control (0.15-Hz: P=0.04 at 10 min;
      0.16-Hz: P<0.001 at 10 min, P=0.04 at 25 min). The analgesic effect of LVVA-SM in
      chronic low back pain patients with neuropathic leg pain can be reverse
      translated to a rat model Video abstract: http://links.lww.com/WNR/A453.

PMID- 29381654
TI  - Macroscopic and microscopic diversity of missplicing in the central nervous
      system of patients with myotonic dystrophy type 1.
AB  - Myotonic dystrophy type I (DM1) is a multiorgan disease caused by CTG-repeat
      expansion in the DMPK gene. Sequestration of the splicing factor MBNL1 results in
      aberrant splicing in many genes in DM1 skeletal muscle, whereas MBNL2 plays a
      leading role in missplicing in the central nervous system (CNS) of patients with
      DM1. Splicing misregulation of most MBNL2-regulated genes occurs in the temporal
      cortex but not in the cerebellum of autopsied patients with DM1. To understand
      the diversity at macroscopic and microscopic levels in CNS of patients with DM1.
      Using autopsied brain tissues, we examined alternative splicing ratios of MBNL2
      regulated genes and expression levels of potential splicing factors. We found
      differences in splicing abnormalities among tested regions of the CNS from
      patients with DM1. In the frontal and temporal cortices and the hippocampus, many
      genes were aberrantly spliced, but severity differed among the brain regions. By
      contrast, there were no significant differences in the ratio of splicing variants
      for most of the genes in the cerebellar cortex and spinal cord between DM1 and
      control samples. We failed to find any change in the amount of potential factors
      (MBNL and CUGBP proteins and DMPK mRNA) which explain the modest missplicing in
      the cerebellum. LASER capture microdissection demonstrated splicing misregulation
      in the molecular layer of the cerebellum but not in the granular layer. This is
      the first study to reveal missplicing in a functional cell layer of DM1 and to
      compare splicing misregulation in a wide region of the CNS using statistical
      analysis.

PMID- 29381655
TI  - Integrated analysis of the genetic basis of suicidal behavior: what has been
      shown by structural genetic studies so far.
AB  - OBJECTIVE: In recent decades, the role of genetic factors in the predisposition
      to suicidal behavior has attracted considerable attention. Although each genetic
      investigation appears to be valuable, no one study on its own can comprehensively
      explain the etiology of suicidal behavior. METHODS: In this study, using a broad
      literature review, we found the suicide-associated gene coexpression network. In
      addition, cytoband, molecular function, biological process, cellular component,
      tissue-based expression, and disease/disorder enrichment analyses were carried
      out to determine the most central cellular and molecular infrastructures involved
      in suicidal behavior. RESULTS: The reconstructed network consisted of 104 genes,
      including 91 previously known genes and 13 novel genes, and 354 interactions.
      Topological analysis showed that in total, CCK, INPP1, DDC, and NPY genes are the
      most fundamental hubs in the network. We found that suicide genes are
      significantly concentrated within chromosomes 11 and 6. Further analysis showed
      that monoaminergic signal transduction, especially through GPCRs, in the
      cingulate gyrus, superior prefrontal gyrus, dorsal striatum, and the cerebellum
      are the main, deficient routes in suicide. Moreover, it turned out that
      genetically, suicidal behavior is more likely in patients with mood and affective
      disorders. CONCLUSION: Like other behavioral disorders, suicide has a complex and
      multifactorial basis and at present, the only approaches to the integrated study
      of such disorders are computer-based methods. The results of such studies,
      although subject to a degree of uncertainty, however, can pave the way for future
      basic and clinical studies.

PMID- 29381656
TI  - No association of NR3C1 polymorphisms with major depressive disorder in the
      Chinese Han population.

PMID- 29381657
TI  - Socioeconomic Status and Cardiovascular Responses to Standardized Stressors: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Disparities in cardiovascular health by socioeconomic status (SES) are
      a pressing public health concern. Hypothesized mechanisms linking low SES to poor
      health are large cardiovascular responses to and delayed recovery from
      psychological stress. The current study presents a meta-analysis of the
      literature on the association of SES with blood pressure and heart rate
      reactivity to and recovery from acute stress tasks. METHODS: The PubMed database
      was searched, and 26 unique studies with relevant data were identified (k = 25
      reactivity [n = 14,617], k = 6 recovery [n = 1,324]). RESULTS: Using random
      effects models, no significant association between SES and cardiovascular
      reactivity to stress emerged (r = .008, 95% confidence interval = -.02 to .04),
      although higher SES was associated with better recovery from stress (r = -.14,
      95% confidence interval -.23 to -.05). Stressor type moderated the reactivity
      effect, wherein higher SES was associated with greater reactivity to cognitive
      stressors (r = .036, p = .024), not with reactivity to interpersonal stressors (r
      = -.02, p = .62), but was associated with lower reactivity to tasks with
      combinations of cognitive, interpersonal, and physical challenges (r = -.12, p =
      .029). Accounting for publication bias revealed a significant association between
      SES and reactivity in the opposite direction of hypotheses. CONCLUSIONS:
      Cardiovascular recovery from acute stress, but not reactivity to stress, may be a
      key pathway between low SES and risk for cardiovascular diseases. Heterogeneity
      in effect size and direction, challenges related to working across temporal
      dynamics, and recommendations for future research are discussed.

PMID- 29381659
TI  - The Interaction of Genetic Predisposition and Socioeconomic Position With Type 2
      Diabetes Mellitus: Cross-Sectional and Longitudinal Analyses From the Lifelines
      Cohort and Biobank Study.
AB  - OBJECTIVE: A strong genetic predisposition for type 2 diabetes mellitus (T2DM)
      may aggravate the negative effects of low socioeconomic position (SEP) in the
      etiology of the disorder. This study aimed to examine cross-sectional and
      longitudinal associations and interactions of a genetic risk score (GRS) and SEP
      with T2DM and to investigate whether clinical and behavioral risk factors can
      explain these associations and interactions. METHODS: We used data from 13,027
      genotyped participants from the Lifelines study. The GRS was based on single
      nucleotide polymorphisms genome-wide associated with T2DM and was categorized
      into tertiles. SEP was measured as educational level. T2DM was based on
      biological markers, recorded medication use, and self-reports. Cross-sectional
      and longitudinal associations and interactions between the GRS and SEP on T2DM
      were examined. RESULTS: The combination of a high GRS and low SEP had the
      strongest association with T2DM in cross-sectional (odds ratio = 3.84, 95%
      confidence interval = 2.28-6.46) and longitudinal analyses (hazard ratio = 2.71,
      1.39-5.27), compared with a low GRS and high SEP. Interaction between a high GRS
      and a low SEP was observed in cross-sectional (relative excess risk due to
      interaction = 1.85, 0.65-3.05) but not in longitudinal analyses. Clinical and
      behavioral risk factors mostly explained the observed associations and
      interactions. CONCLUSIONS: A high GRS combined with a low SEP provides the
      highest risk for T2DM. These factors also exacerbated each other's impact cross
      sectionally but not longitudinally. Preventive measures should target individual
      and contextual factors of this high-risk group to reduce the risk of T2DM.

PMID- 29381660
TI  - Prevalence of hormone therapy, factors associated with its use, and knowledge
      about menopause: a population-based household survey.
AB  - OBJECTIVE: The aim of the study was to assess the prevalence of hormone therapy
      (HT), the factors associated with its use, and the importance of knowledge about
      menopause and HT. METHODS: A cross-sectional population-based study with 749
      Brazilian women aged 45 to 60 years living in the Campinas Metropolitan Region
      was carried out between September 2012 and June 2013. The dependent variable was
      current or previous HT use. The independent variables were sociodemographic data,
      health-related problems, and knowledge about menopause assessed using a score
      that was obtained with a questionnaire on various aspects of menopause. RESULTS:
      The mean age of the women was 52.5 (+/-4.4) years. With regard to the menopause
      status, 16% were premenopausal, 16% were perimenopausal, and 68% were
      postmenopausal. Among all the women included, 19.5% reported current or previous
      HT use. In multiple regression analysis, being postmenopausal (prevalence ratio
      [PR] 2.76; 95% CI, 1.74-4.38), receiving information about menopause from
      physicians and health service workers (PR 2.73; 95% CI, 1.91-3.89), having
      bilateral oophorectomy (PR 2.18; 95% CI, 1.49-3.17), experiencing work
      interruption due to hot flashes (PR 1.44; 95% CI, 1.03-2.01), and having
      extensive knowledge about menopause (PR 1.12; 95% CI, 1.05-1.19) were associated
      with a higher prevalence of HT use. CONCLUSIONS: The prevalence of HT use was
      19.5%. Menopause status, information source, surgical menopause, work
      interruption due to hot flashes, and knowledge about menopause were associated
      with HT use. Education promoted by healthcare systems can increase HT use in
      women who have indications for treatment.

PMID- 29381658
TI  - Cardiovascular Stress Reactivity and Carotid Intima-Media Thickness: The
      Buffering Role of Slow-Wave Sleep.
AB  - OBJECTIVE: Exaggerated cardiovascular reactivity to acute psychological stress
      has been associated with increased carotid intima-media thickness (IMT). However,
      interstudy variability in this relationship suggests the presence of moderating
      factors. The current study aimed to test the hypothesis that poor nocturnal
      sleep, defined as short total sleep time or low slow-wave sleep, would moderate
      the relationship between cardiovascular reactivity and IMT. METHODS: Participants
      (N = 99, 65.7% female, age = 59.3 +/- 9.3 years) completed a two-night laboratory
      sleep study and cardiovascular examination where sleep and IMT were measured. The
      multisource interference task was used to induce acute psychological stress,
      while systolic and diastolic blood pressure and heart rate were monitored.
      Moderation was tested using the PROCESS framework in SPSS. RESULTS: Slow-wave
      sleep significantly moderated the relationship between all cardiovascular stress
      reactivity variables and IMT (all pinteraction <= .048, all DeltaRinteraction >=
      .027). Greater stress reactivity was associated with higher IMT values in the low
      slow-wave sleep group and lower IMT values in the high slow-wave sleep group. No
      moderating effects of total sleep time were observed. CONCLUSIONS: The results
      provide evidence that nocturnal slow-wave sleep moderates the relationship
      between cardiovascular stress reactivity and IMT and may buffer the effect of
      daytime stress-related disease processes.

PMID- 29381661
TI  - Perspectives and decision-making about menopausal therapies in women who had
      bilateral oophorectomy.
AB  - OBJECTIVE: The aim of the study was to explore the process of decision-making
      about menopausal treatments in women who have had surgical menopause as a result
      of bilateral oophorectomy (<=50 y). METHODS: We used a descriptive qualitative
      research design. Women who had a surgical menopause were purposefully selected
      from the Edmonton Menopause Clinics. Focus groups were held, each with six to
      nine participants. All sessions were audio-recorded and transcribed verbatim.
      Data were analyzed using qualitative content analysis. RESULTS: We conducted five
      focus groups from June 30 to July 21, 2016 (N = 37). One-third of the women had
      the surgery within the last 5 years. Almost all women had a concurrent
      hysterectomy (97%) and were current users of hormone therapy (70%). Four main
      themes identified were "perceptions of surgical menopause," "perceptions of
      received support," "being my own advocate," and "concept of adequate support."
      Women shared that the experience was worse than their expectations and did not
      believe they were given adequate support to prepare them to make therapy
      decisions. Women had to "be their own advocates" and seek support from within the
      healthcare system and outside to cope with their health issues. To make an
      informed decision about treatments postsurgery, women expressed a need to learn
      more about the symptoms of surgical menopause, treatment options, resources,
      avenues for support, and stories of similar experiences, preferably before the
      surgery. CONCLUSIONS: We identified several modifiable deterrents to decision
      making in early surgical menopause which can help inform the development of a
      patient decision aid for this context.

PMID- 29381663
TI  - The Women's Health Initiative: addressing vaginal and sexual health.

PMID- 29381662
TI  - Association between HIV status and psychological symptoms in perimenopausal
      women.
AB  - OBJECTIVE: HIV-infected women are burdened by depression and anxiety, which may
      impact adherence to antiretroviral therapy and overall quality of life. Yet,
      little is known about the scope of psychological symptoms in the growing number
      of HIV-infected women reaching menopause, when affective symptoms are more
      prevalent in the general population. We conducted a longitudinal study to compare
      affective symptoms between perimenopausal HIV-infected and non-HIV-infected
      women. METHODS: The Center for Epidemiologic Studies Depression Scale (CES-D),
      and the Generalized Anxiety Disorder scale (GAD-7) were completed at baseline and
      12 months among 33 HIV-infected and 33 non-HIV-infected perimenopausal women
      matched by race, age, menstrual patterns, and BMI. Linear regression models
      estimated the relationship of baseline GAD-7 and CES-D scores with clinical
      factors. RESULTS: All women were perimenopausal at baseline, and the vast
      majority remained perimenopausal throughout follow-up. HIV status was associated
      with higher baseline CES-D scores (median [interquartile range] 21 [12, 29] vs 10
      [5, 14]; P = 0.03) and GAD-7 scores (7 [5, 15] vs 2 [1, 7]; P = 0.01),
      controlling for smoking, substance use, and antidepressant use. Depressive
      symptoms and anxiety remained significantly higher in the HIV-infected women at
      12 months (P <= 0.01). Significant relationships of depressive symptoms (P =
      0.048) and anxiety (P = 0.02) with hot flash severity were also observed.
      CONCLUSIONS: Perimenopausal HIV-infected women experienced a disproportionately
      high level of affective symptom burden over a 12-month observation period. Given
      the potential for these factors to influence adherence to HIV clinical care and
      quality of life, careful assessment and referral for treatment of these symptoms
      is essential.

PMID- 29381664
TI  - Hormone therapy and urine protein excretion: a multiracial cohort study,
      systematic review, and meta-analysis.
AB  - OBJECTIVE: Experimental models suggest estrogen has a renoprotective effect, but
      human studies show variable results. Our objective was to study the association
      of hormone therapy (HT) and albuminuria in postmenopausal women and to synthesize
      the results with outcomes from prior studies. METHODS: We analyzed data from
      postmenopausal women who participated in the second study visit (2000-2004) of
      the Genetic Epidemiology Network of Arteriopathy (GENOA) study. The exposure was
      self-reported HT use and the outcome was albuminuria (urine albumin-to-creatinine
      ratio >25 mg/g creatinine). We also conducted a systematic review and meta
      analysis on the association of HT and urine protein in postmenopausal women.
      Continuous and dichotomous measures of protein excretion were converted to a
      standardized mean difference (SMD) for each study. RESULTS: In the GENOA cohort
      (n = 2,217), there were fewer women with albuminuria among HT users than nonusers
      (9% vs 19%, P < 0.001). HT use was associated with decreased odds of albuminuria
      (odds ratio 0.65, 95% confidence interval (CI), 0.45-0.95), after adjusting for
      significant differences in age, race, education, comorbidities, and the age at
      and cause of menopause. The SMD of the effect of HT on urine
      proteinuria/albuminuria in the randomized control trials (n = 3) was 0.02 (95%
      CI, -0.29 to 0.33) and -0.13 (95% CI, -0.31 to 0.05) in the observational studies
      (n = 9). There was significantly less albuminuria among HT users (SMD -0.15, 95%
      CI, -0.27 to -0.04) in the 9 studies that only reported albuminuria as an outcome
      and in the 10 studies with a comparator arm (SMD -0.15, 95% CI, -0.26 to -0.04).
      CONCLUSIONS: HT is associated with decreased odds of albuminuria, but some of the
      observed benefits may be related to reported outcomes, the presence of a
      comparator arm, and the type of study design.

PMID- 29381665
TI  - What's in a name: are menopausal "hot flashes" a symptom of menopause or a
      manifestation of neurovascular dysregulation?
AB  - Hot flashes have typically been classified as "symptoms of menopause" that should
      be tolerated or treated until they resolve. However, mounting evidence points to
      hot flashes as a manifestation of one or several underlying pathophysiological
      processes. Associations exist between the presence, timing of onset, severity,
      and duration of hot flashes, and the risk of several neurological (affecting
      sleep, mood, and cognition) and cardiovascular conditions. In addition, four
      consistent patterns of vasomotor disturbances have been identified across
      different countries, making it unlikely that these patterns are solely explained
      by socioeconomic or cultural factors. The changing hormonal environment of
      menopause may unmask differences in the autonomic neurovascular control
      mechanisms that put an individual woman at risk for chronic conditions of aging.
      These differences may have a genetic basis or may be acquired across the life
      span and are consistent with the variability of the clinical manifestations of
      aging observed in women after bilateral oophorectomy. It is time to investigate
      the pathophysiological mechanisms underlying the four patterns of vasomotor
      symptoms more closely, and to shift from describing hot flashes as symptoms to be
      tolerated to manifestations of an underlying autonomic neurovascular
      dysregulation that need to be addressed.

PMID- 29381667
TI  - Constipation and diarrhea during the menopause transition and early
      postmenopause: observations from the Seattle Midlife Women's Health Study.
AB  - OBJECTIVE: To assess the relationship of constipation and diarrhea severity
      during the menopause transition (MT) with age, MT stage, reproductive biomarkers,
      stress-related biomarkers, and stress-related perceptions. METHODS: From 1990 to
      1992, women aged 35 to 55 years were recruited from the greater Seattle area; 291
      of them consented to ongoing (1990-2013) annual data collection by daily
      menstrual calendar, health diary, and annual health questionnaire. A subset (n =
      131) provided a first morning voided urine specimen (1997-2013). These were
      assayed for levels of E1G, follicle-stimulating hormone, testosterone, cortisol,
      norepinephrine, and epinephrine. Mixed-effects modeling was used to identify how
      changes in constipation and diarrhea severity over time related to age, MT stage,
      reproductive biomarkers, stress-related biomarkers, and stress-related
      perceptions. RESULTS: In a univariate model, age, late reproductive (LR) stage,
      tension, and anxiety were all significantly and positively related to
      constipation severity, whereas cortisol was significantly and negatively
      associated. In a multivariate model, only tension and cortisol remained
      significant predictors of constipation severity (P < 0.05). In a univariate
      model, age, LR stage, and estrone glucuronide were significantly and negatively
      associated with diarrhea severity, whereas tension, anxiety, and perceived stress
      were significantly and positively related. In a multivariate model, only tension
      and age remained significant predictors of diarrhea severity. CONCLUSIONS: Key
      reproductive hormones do not play a significant role in constipation or diarrhea
      severity in the MT. In contrast, stress perception, tension, anxiety, and
      cortisol do. These factors should be evaluated in further research involving
      constipation and diarrhea.

PMID- 29381666
TI  - Effects of oral conjugated equine estrogens with or without medroxyprogesterone
      acetate on incident hypertension in the Women's Health Initiative hormone therapy
      trials.
AB  - OBJECTIVE: The aim of the study was to determine the effect of menopausal hormone
      therapy on incident hypertension in the two Women's Health Initiative hormone
      therapy trials and in extended postintervention follow-up. METHODS: A total of
      27,347 postmenopausal women aged 50 to 79 years were enrolled at 40 US centers.
      This analysis includes the subsample of 18,015 women who did not report
      hypertension at baseline and were not taking antihypertensive medication. Women
      with an intact uterus received conjugated equine estrogens (CEE; 0.625 mg/d) plus
      medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 5,994) or placebo (n = 5,679).
      Women with prior hysterectomy received CEE alone (0.625 mg/d) (n = 3,108) or
      placebo (n = 3,234). The intervention lasted a median of 5.6 years in the CEE
      plus MPA trial and 7.2 years in the CEE-alone trial with 13 years of cumulative
      follow-up until September 30, 2010. The primary outcome for these analyses was
      self-report of a new diagnosis of hypertension and/or high blood pressure
      requiring treatment with medication. RESULTS: During the CEE and CEE plus MPA
      intervention phase, the rate of incident hypertension was 18% higher for
      intervention than for placebo (CEE: hazard ratio [HR], 1.18; 95% CI, 1.09-1.29;
      CEE plus MPA: HR, 1.18; 95% CI, 1.09-1.27). This effect dissipated
      postintervention in both trials (CEE: HR, 1.06; 95% CI, 0.94-1.20; CEE plus MPA:
      HR, 1.02; 95% CI, 0.94-1.10). CONCLUSIONS: CEE (0.625 mg/d) administered orally,
      with or without MPA, is associated with an increased risk of hypertension in
      older postmenopausal women. Whether lower doses, different estrogen formulations,
      or transdermal route of administration offer lower risks warrant further study.

PMID- 29381668
TI  - Sometimes "Improvement" is Not Enough: The Jimmo Settlement.
AB  - The Jimmo Settlement is about the erroneous, but pervasively used, "improvement
      standard" of the past 30 years. In essence, Medicare beneficiaries were being
      denied skilled services if they did not have the capacity to improve, or more
      clinically described as "lack of restoration potential." The Centers for Medicare
      & Medicaid Services (CMS) has a webpage clarifying this misconception and about
      the Jimmo Settlement; it contains links that shed light on this issue. The link,
      https://www.cms.gov/Center/Special-Topic/Jimmo-Center.html, is the official CMS
      webpage about the Jimmo Settlement and has information for the case manager to
      peruse.

PMID- 29381669
TI  - Hospital Discharge and Selecting a Skilled Nursing Facility: A Comparison of
      Experiences and Perspectives of Patients and Their Families.
AB  - PURPOSE OF STUDY: A currently proposed rule by the Centers for Medicare &
      Medicaid Services would require providers to devote more resources to discharge
      planning from hospitals to ensure the prioritization of patient preferences and
      goals in the discharge planning process. Annually, more than 3 million persons
      enter a nursing home in the United States, with the vast majority of patients
      coming directly from hospitals. Although early evidence suggests more family
      involvement than patient involvement in the discharge process, most of this work
      has relied on retrospective reports of the decision-making process postplacement.
      This article seeks to examine and compare the experiences and perspectives of
      patients and others involved in the selection of the nursing home (predominately
      adult children and spouses). PRIMARY PRACTICE SETTING: Large academic medical
      hospital with patients being discharged to a skilled nursing facility.
      METHODOLOGY AND SAMPLE: A total of 225 patients or their family members and
      involved others who completed an exit survey assessing their experiences and
      perspectives in selecting a skilled nursing home and in experiencing the
      discharge process more generally. RESULTS: Patients were the primary decision
      makers about 23% of the time but were often involved in the decision even when
      family members/involved others were primarily making decisions in the discharge
      process. Although patients were involved in the selection of the nursing home to
      a lesser degree than involved others, their level of satisfaction with the
      decision to be discharged to a skilled nursing home and their level of
      satisfaction with their personal level of involvement with the selection of the
      specific nursing home did not differ from the satisfaction ratings of the
      involved others. Furthermore, their confidence in the decision and their
      satisfaction with the decision did not differ from ratings provided by family
      members/involved others. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE:
      Recommendations for case management practice include (1) encouraging patients and
      their families to take an active role in the discharge process; (2) incorporating
      technology into the discharge process that promotes this active level of
      engagement; and (3) facilitating access to data to promote discharge to the
      highest quality nursing homes available.

PMID- 29381670
TI  - Predictors of Caregiver Distress in the Community Setting Using the Home Care
      Version of the Resident Assessment Instrument.
AB  - PURPOSE OF STUDY: The purpose of this study was to identify factors predictive of
      new onset and improved caregiver distress among informal caregivers providing
      assistance for clients receiving home care. PRIMARY PRACTICE SETTINGS: Home care.
      METHODOLOGY AND SAMPLE: The sample included 323,409 clients receiving home care
      from a Community Care Access Centre between March 2002 and March 2015 for whom
      data were available from two subsequent Resident Assessment Instrument-Home Care
      (RAI-HC) assessments. Separate multivariate logistic regression models were
      created for onset of and improvement in caregiver distress. RESULTS: Variables
      that increase the odds in onset of caregiver distress included primary caregiver
      is not satisfied with support received from family and friends; client lives with
      primary caregiver; 65 years and older; has Alzheimer and other related dementia;
      has condition or disease that makes cognition, activities of daily living, mood,
      or behavior patterns unstable; took sedatives in the last 7 days; Method for
      Assigning Priority Levels (MAPLe) score 4 or more; demonstrates persistent anger;
      has difficulty using the telephone; is married; requires 20 hr or more of
      informal help weekly; and Clinical Risk Scale score 4 or more. Variables that
      increased the odds of improved caregiver distress include client now lives with
      other persons (as compared with 90 days ago); demonstrates good prospects for
      recovery; treatment changes in last 30 days; surgical wound; female; one or more
      hospital visits in last 90 days; greater number of months between RAI-HC
      assessments; and two or more hours of physical activities in the last 3 days.
      Variables that decreased the odds of improved caregiver distress (i.e.,
      persistent distress) include MAPLe score 4 or more; persistent anger; difficulty
      using telephone; Alzheimer, related dementia; requires interpreter; and lives
      with primary caregiver. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Informal
      caregivers provide essential support for home care clients. Factors predictive of
      new onset and improved caregiver distress can be used by case managers for
      comprehensive care planning that addresses the collective needs of the client
      caregiver dyad.

PMID- 29381671
TI  - Appointment Reminders to Decrease 30-Day Readmission Rates to Inpatient
      Psychiatric Hospitals.
AB  - PURPOSE OF PROJECT: The purpose of this quality improvement project was to reduce
      30-day readmission rates to inpatient psychiatric hospitals by standardizing
      discharge processes by including scheduling outpatient psychiatric appointments
      for all patients at discharge and also to include the mailing postal reminders to
      prompt patients to attend their first outpatient mental health appointment
      following treatment. PRIMARY PRACTICE SETTING: Inpatient psychiatric hospital.
      METHODOLOGY AND SAMPLE: The project design was an analysis of readmission data
      obtained both 3 months before and after implementation of the postal reminder
      letters. This project took place at a 50-bed inpatient psychiatric hospital in
      the southeastern United States that accepts male and female adult patients with
      mental health and substance abuse disorders. RESULTS: The implementation of an
      appointment reminder letter resulted in a slight decrease in 30-day readmission
      rates. The average readmission rate 3 months prior to implementation was 10%. The
      average readmission rate 3 months postdischarge was 9%. December 2015 was
      included in the postimplementation data. December historically has higher rates
      of 30-day readmissions at this facility. If this month had been excluded, more
      dramatic decrease in 30-day readmission rates could be observed. IMPLICATIONS FOR
      CASE MANAGEMENT PRACTICE: Future implications for case management practice could
      include the usage of reminder prompts via telephone communication or text
      messaging in conjunction with postal reminders. The psychiatric population can be
      particularly challenging when considering increased risk for readmission within
      30 days and also the impending pay-for-performance quality measures, which are
      soon to be implemented. Measures should be taken now to ensure that readmission
      rates decrease, not only to promote better patient outcomes, but also as a cost
      saving measure. Although many variables may contribute to the risk for 30-day
      readmission rates including medication noncompliance, lack of proper follow-up,
      as well as seasonal trends, the postal appointment reminder letters may further
      decrease 30-day readmission rates. Other care management strategies combined with
      reminder letters may further address barriers that may exist to not only improve
      patient outcomes, but also to further reduce readmission rates. It is also
      important to mention that there are further implications that could be directly
      contributed to specific social determinants of health specific to the psychiatric
      population. For example, access to prescribed medications and transportation to
      appointments should be addressed to further reduce readmission rates for this
      vulnerable population.

PMID- 29381672
TI  - Simulated Interprofessional Education Discharge Planning Meeting to Improve
      Skills Necessary for Effective Interprofessional Practice.
AB  - PURPOSE OF STUDY: The purpose of this study was to evaluate the use of a
      simulation-enhanced interprofessional education (Sim-IPE) discharge planning
      learning experience using simulated patients (SPs), to explore the ability for
      students to communicate with each other and to a patient/caregiver, and to use
      clinical thinking to make a safe and appropriate interprofessional discharge
      recommendation. PRIMARY PRACTICE SETTING(S): Educational institution; university
      simulation center. METHODOLOGY AND SAMPLE: A Sim-IPE was performed with students
      from physical therapy (N = 46), nursing (N = 25), and social work (N = 11).
      Students were placed into interprofessional teams. Presimulation, each student
      was expected to complete a survey and review several items including the patient
      case, a communication strategy, and community resources. The team then interacted
      with SPs portraying the patient and the family member. Postsimulation,
      facilitators led a debriefing session and students completed a post-IPE survey.
      The Interprofessional Collaborative Competency Attainment Survey (ICCAS) was
      completed pre- and postexperience. RESULTS: Most students reported that they
      strongly or somewhat agreed that the experience improved their clinical thinking
      skills (67%; n = 55), improved awareness of the patient voice in shared decision
      making (72.8%; n = 59), improved ability to prioritize patient's list of
      impairments (75.3%; n = 61), and improved confidence with discharge planning
      (69.1%; n = 56). IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Discharge planning is
      inherently an interprofessional process. Utilizing a simulation as a method to
      practice discharge planning may have a positive impact on future clinical
      practice. Completing the ICCAS may not be the appropriate assessment when
      evaluating change before and after an IPE experience based on the high scores
      noted preexperience. The use of a simulated discharge planning meeting may
      improve skills necessary for effective interprofessional practice.

PMID- 29381674
TI  - It is in Our DNA.

PMID- 29381675
TI  - Can Regulation Solve the Opioid Crisis?

PMID- 29381676
TI  - Seizing "Teachable Moments": Talent Development in Case Management.

PMID- 29381677
TI  - Improved Case Manager Satisfaction by Stratification of Case Load.

PMID- 29381680
TI  - Use of Volar Locking Plate Versus Intramedullary Nailing for Fixation of Distal
      Radius Fractures: A Retrospective Analysis of Clinical and Radiographic Outcomes.
AB  - BACKGROUND The objective of this study was to evaluate clinical and radiographic
      outcomes of volar plate versus intramedullary nailing for fixation of distal
      radius fractures. MATERIAL AND METHODS This retrospective study included 64
      patients with extra-articular and simple intra-articular fractures of the distal
      radius who underwent intramedullary fixation using volar locking plate (n=35,
      mean age 47.3+/-16.4 years, 82.9% female) or intramedullary nailing (n=29, mean
      age 51.3+/-10.1 years, 58.6% female). Outcome measures were range of motion
      (ROM); visual analog scale (VAS); Disabilities of the Arm, Shoulder, and Hand
      (DASH) score; Gartland-Werley score; Stewart score; and radiographic findings.
      RESULTS Time to fracture union was 5.5+/-1.2 and 5.2+/-0.6 weeks after volar
      plate fixation and intramedullary nailing, respectively (p>0.05). Compared to
      volar plate fixation, intramedullary nailing provided better restoration of volar
      tilt (6.9+/-6.3 degrees  vs. 9.4+/-1.6 degrees , p=0.004) and wrist flexion
      (74.3+/-15.1 degrees  vs. 67.9+/-13.1 degrees , p=0.003). However, volar plate
      fixation was significantly better in restoration of supination (85.0+/-8.3
      degrees  vs. 81.9+/-5.1 degrees , p=0.001) and radio-ulnar variance (0.7+/-0.8 mm
      vs. 1.1+/-0.9 mm, p=0.05), DASH score (9.2+/- 9.0 vs. 15.0 +/-3.3, p=0.035), and
      Gartland-Werley score (1.8+/-0.9 vs. 4.9+/-5.4, p=0.004). Volar plate and
      intramedullary nailing groups were comparable with respect to Stewart score
      (1.5+/-0.7 and 1.6+/-1.3, p>0.05) and complication rates (34.3% vs. 37.9%,
      p>0.05). CONCLUSIONS Both volar plate fixation and intramedullary nail fixation
      provide good clinical and radiographic outcomes for primarily extra-articular or
      simple intra-articular distal radius fractures. As intramedullary nailing
      provides better restoration of volar tilt and wrist flexion, volar plate fixation
      provides better restoration of radio-ulnar variance and wrist supination.

PMID- 29381681
TI  - Human ex vivo prostate tissue model system identifies ING3 as an oncoprotein.
AB  - BACKGROUND: Although the founding members of the INhibitor of Growth (ING) family
      of histone mark readers, ING1 and ING2, were defined as tumour suppressors in
      animal models, the role of other ING proteins in cellular proliferation and
      cancer progression is unclear. METHODS: We transduced ex vivo benign prostate
      hyperplasia tissues with inducible lentiviral particles to express ING proteins.
      Proliferation was assessed by H3S10phos immunohistochemistry (IHC). The
      expression of ING3 was assessed by IHC on a human prostate cancer tissue
      microarray (TMA). Gene expression was measured by DNA microarray and validated by
      real-time qPCR. RESULTS: We found that ING3 stimulates cellular proliferation in
      ex vivo tissues, suggesting that ING3 could be oncogenic. Indeed, ING3
      overexpression transformed normal human dermal fibroblasts. We observed elevated
      levels of ING3 in prostate cancer samples, which correlated with poorer patient
      survival. Consistent with an oncogenic role, gene-silencing experiments revealed
      that ING3 is required for the proliferation of breast, ovarian, and prostate
      cancer cells. Finally, ING3 controls the expression of an intricate network of
      cell cycle genes by associating with chromatin modifiers and the H3K4me3 mark at
      transcriptional start sites. CONCLUSIONS: Our investigations create a shift in
      the prevailing view that ING proteins are tumour suppressors and redefine ING3 as
      an oncoprotein.

PMID- 29381682
TI  - Treatment with docetaxel in combination with Aneustat leads to potent inhibition
      of metastasis in a patient-derived xenograft model of advanced prostate cancer.
AB  - BACKGROUND: Docetaxel used for first-line treatment of advanced prostate cancer
      (PCa) is only marginally effective. We previously showed, using the LTL-313H
      subrenal capsule patient-derived metastatic PCa xenograft model, that docetaxel
      combined with Aneustat (OMN54), a multivalent plant-derived therapeutic, led to
      marked synergistic tumour growth inhibition. Here, we investigated the effect of
      docetaxel+Aneustat on metastasis. METHODS: C4-2 cells were incubated with
      docetaxel, Aneustat and docetaxel+Aneustat to assess effects on cell migration.
      The LTL-313H model, similarly treated, was analysed for effects on lung micro
      metastasis and kidney invasion. The LTL-313H gene expression profile was compared
      with profiles of PCa patients (obtained from Oncomine) and subjected to IPA to
      determine involvement of cancer driver genes. RESULTS: Docetaxel+Aneustat
      markedly inhibited C4-2 cell migration and LTL-313H lung micro-metastasis/kidney
      invasion. Oncomine analysis indicated that treatment with docetaxel+Aneustat was
      associated with improved patient outcome. The drug combination markedly
      downregulated expression of cancer driver genes such as FOXM1 (and FOXM1-target
      genes). FOXM1 overexpression reduced the anti-metastatic activity of
      docetaxel+Aneustat. CONCLUSIONS: Docetaxel+Aneustat can inhibit PCa tissue
      invasion and metastasis. This activity appears to be based on reduced expression
      of cancer driver genes such as FOXM1. Use of docetaxel+Aneustat may provide a
      new, more effective regimen for therapy of metastatic PCa.

PMID- 29381683
TI  - External validation of risk prediction models for incident colorectal cancer
      using UK Biobank.
AB  - BACKGROUND: This study aimed to compare and externally validate risk scores
      developed to predict incident colorectal cancer (CRC) that include variables
      routinely available or easily obtainable via self-completed questionnaire.
      METHODS: External validation of fourteen risk models from a previous systematic
      review in 373 112 men and women within the UK Biobank cohort with 5-year follow
      up, no prior history of CRC and data for incidence of CRC through linkage to
      national cancer registries. RESULTS: There were 1719 (0.46%) cases of incident
      CRC. The performance of the risk models varied substantially. In men, the
      QCancer10 model and models by Tao, Driver and Ma all had an area under the
      receiver operating characteristic curve (AUC) between 0.67 and 0.70.
      Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma
      models were the best performing with AUCs between 0.63 and 0.66. Assessment of
      calibration was possible for six models in men and women. All would require
      country-specific recalibration if estimates of absolute risks were to be given to
      individuals. CONCLUSIONS: Several risk models based on easily obtainable data
      have relatively good discrimination in a UK population. Modelling studies are now
      required to estimate the potential health benefits and cost-effectiveness of
      implementing stratified risk-based CRC screening.

PMID- 29381684
TI  - Indeterminate nodules in osteosarcoma: what's the follow-up?
AB  - BACKGROUND: Indeterminate pulmonary nodules in patients diagnosed with
      osteosarcoma present a challenge for accurate staging and prognosis. The aim of
      this study was to explore the significance of this finding. METHODS: A
      retrospective cohort study of 120 patients with osteosarcoma was performed in the
      North East of England. Chest computed tomographies (CTs) at presentation were
      reviewed and the incidence of 'indeterminate' nodules recorded. Follow-up scans
      were reviewed and survival as well as prognostic features were analysed. RESULTS:
      25% of our cohort presented with indeterminate nodules. Of these, 33% were
      subsequently confirmed as metastases, the majority within a year. Kaplan-Meier
      survival analysis showed that patients with indeterminate nodules fared better
      than those with frank metastatic disease, and similar to those who presented with
      a normal chest CT. We found no radiographic features that predicted survival.
      CONCLUSIONS: Indeterminate nodules remain a clinical and diagnostic dilemma.
      Close monitoring of patients is advised during the first year from presentation,
      and there is potential for indeterminate nodules to develop into frank metastases
      later than five years from presentation.

PMID- 29381685
TI  - High burden of subsequent malignant neoplasms and cardiovascular disease in long
      term Hodgkin lymphoma survivors.
AB  - This corrects the article DOI: 10.1038/bjc.2017.85.

PMID- 29381686
TI  - WNT5A induces castration-resistant prostate cancer via CCL2 and tumour
      infiltrating macrophages.
AB  - BACKGROUND: Although the standard treatment for the patients with recurrent and
      metastatic prostate cancer (CaP) is androgen deprivation therapy, castration
      resistant prostate cancer (CRPC) eventually emerges. Our previous report
      indicated that bone morphogenetic protein 6 (BMP6) induced CRPC via tumour
      infiltrating macrophages. In a separate line of study, we have observed that the
      WNT5A/BMP6 loop in CaP bone metastasis mediates resistance to androgen
      deprivation in tissue culture. Simultaneously, we have reported that BMP6 induced
      castration resistance in CaP cells via tumour-infiltrating macrophages.
      Therefore, our present study aims to investigate the mechanism of WNT5A and its
      interaction with macrophages on CRPC. METHODS: Doxycycline inducible WNT5A
      overexpression prostate cancer cell line was used for detailed mechanical study.
      RESULTS: WNT5A was associated with increased expression of chemokine ligand 2
      (CCL2) in the human CaP cell line, LNCaP. Mechanistically, this induction of CCL2
      by WNT5A is likely to be mediated via the mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinase (ERK) signalling pathway. Our in
      vivo experiments demonstrated that the overexpression of WNT5A in LNCaP cells
      promoted castration resistance. Conversely, this resistance was inhibited with
      the removal of macrophages via clodronate liposomes. When patient-derived CaP
      LuCaP xenografts were analysed, high levels of WNT5A were correlated with
      increased levels of CCL2 and BMP6. In addition, higher levels of CCL2 and BMP6
      were more commonly observed in intra-femoral transplanted tumours as compared to
      subcutaneous-transplanted tumours in the patient-derived PCSD1 bone-niche model.
      CONCLUSIONS: These findings collectively suggest that WNT5A may be a key gene
      that induces CRPC in the bone niche by recruiting and regulating macrophages
      through CCL2 and BMP6, respectively.

PMID- 29381687
TI  - Enrolling children with acute lymphoblastic leukaemia on a clinical trial
      improves event-free survival: a population-based study.
AB  - BACKGROUND: The objectives of this study were to describe the impact of trial
      enrollment at diagnosis on event-free and overall survival in paediatric acute
      lymphoblastic leukaemic (ALL) using a population-based approach. METHODS: We
      conducted a retrospective cohort study that included children newly diagnosed
      with ALL between 1 and 14 years of age. The data source was the Cancer in Young
      People in Canada (CYP-C) national paediatric cancer population-based database. We
      conducted univariate and multiple Cox proportional hazards models. RESULTS: There
      were 2569 children with ALL; 1408 (54.8%) were enrolled on a clinical trial at
      initial diagnosis. Event-free survival at 5 years was 89.8%+/-0.9 vs 84.1%+/-1.2.
      (P<0.0001) for those enrolled and not enrolled on a clinical trial, respectively.
      Overall survival at 5 years was higher for those enrolled (94.1%+/-0.7) vs not
      enrolled (90.5%+/-1.0; P=0.001). In a model that adjusted for demographic,
      leukaemic and socioeconomic factors, enrollment on trials was significantly
      associated with better event-free survival (hazard ratio (HR) 0.67, 95%
      confidence interval (CI) 0.47-0.95; P=0.023), but not overall survival (HR 0.69,
      95% CI 0.44-1.08; P=0.102). CONCLUSIONS: Event-free survival was significantly
      better in children with ALL enrolled on a clinical trial. Future research should
      identify barriers to clinical trial enrollment for children with ALL.

PMID- 29381688
TI  - Reduced mannosidase MAN1A1 expression leads to aberrant N-glycosylation and
      impaired survival in breast cancer.
AB  - BACKGROUND: Alterations in protein glycosylation have been related to malignant
      transformation and tumour progression. We recently showed that low mRNA levels of
      Golgi alpha-mannosidase MAN1A1 correlate with poor prognosis in breast cancer
      patients. METHODS: We analysed the role of MAN1A1 on a protein level using
      western blot analysis (n=105) and studied the impact of MAN1A1-related
      glycosylation on the prognostic relevance of adhesion molecules involved in
      breast cancer using microarray data (n=194). Functional consequences of
      mannosidase inhibition using the inhibitor kifunensine or MAN1A1 silencing were
      investigated in breast cancer cells in vitro. RESULTS: Patients with low/moderate
      MAN1A1 expression in tumours showed significantly shorter disease-free intervals
      than those with high MAN1A1 levels (P=0.005). Moreover, low MAN1A1 expression
      correlated significantly with nodal status, grading and brain metastasis. At an
      mRNA level, membrane proteins ALCAM and CD24 were only significantly prognostic
      in tumours with high MAN1A1 expression. In vitro, reduced MAN1A1 expression or
      mannosidase inhibition led to a significantly increased adhesion of breast cancer
      cells to endothelial cells. CONCLUSIONS: Our study demonstrates the prognostic
      role of MAN1A1 in breast cancer by affecting the adhesive properties of tumour
      cells and the strong influence of this glycosylation enzyme on the prognostic
      impact of some adhesion proteins.

PMID- 29381689
TI  - Geriatric assessment may help decision-making in elderly patients with
      inoperable, locally advanced non-small-cell lung cancer.
AB  - BACKGROUND: Although concurrent chemoradiotherapy (cCRT) increases survival in
      patients with inoperable, locally advanced non-small-cell lung cancer (NSCLC),
      there is no consensus on the treatment of elderly patients. The aim of this study
      was to determine the prognostic value of the comprehensive geriatric assessment
      (CGA) and its ability to predict toxicity in this setting. METHODS: We enrolled
      85 consecutive elderly (?75 years) participants, who underwent CGA and the
      Vulnerable Elders Survey (VES-13). Those classified as fit and medium-fit by CGA
      were deemed candidates for cCRT (platinum-based chemotherapy concurrent with
      thoracic radiation therapy), while unfit patients received best supportive care.
      RESULTS: Fit (37%) and medium-fit (48%) patients had significantly longer median
      overall survival (mOS) (23.9 and 16.9 months, respectively) than unfit patients
      (15%) (9.3 months, log-rank P=0.01). In multivariate analysis, CGA groups and VES
      13 were independent prognostic factors. Fit and medium-fit patients receiving
      cCRT (n=54) had mOS of 21.1 months (95% confidence interval: 16.2, 26.0). In
      those patients, higher VES-13 (?3) was associated with shorter mOS (16.33 vs 24.3
      months, P=0.027) and higher risk of G3-4 toxicity (65 vs 32%, P=0.028).
      CONCLUSIONS: Comprehensive geriatric assessment and VES-13 showed independent
      prognostic value. Comprehensive geriatric assessment may help to identify elderly
      patients fit enough to be treated with cCRT.

PMID- 29381690
TI  - Pazopanib maintenance after first-line etoposide and platinum chemotherapy in
      patients with extensive disease small-cell lung cancer: a multicentre,
      randomised, placebo-controlled Phase II study (KCSG-LU12-07).
AB  - BACKGROUND: We investigated whether pazopanib maintenance following first-line
      chemotherapy would improve survival in patients with extensive disease small-cell
      lung cancer (ED-SCLC). METHODS: This study is a randomised, placebo-controlled,
      phase II study that enroled ED-SCLC patients who had not progressed after four
      cycles of etoposide plus platinum therapy. Eligible patients were randomly
      assigned (1 : 1 ratio) to either placebo or pazopanib 800 mg per day until
      progression or unacceptable toxicity. The primary end point was progression-free
      survival (PFS). RESULTS: 97 patients were enroled and randomly assigned; 2
      patients did not receive study drugs. In total, 95 patients received maintenance
      therapy (pazopanib, n=48; placebo, n=47) and were included in the analyses. Grade
      3 toxicities for pazopanib maintenance were thrombocytopenia (10.4%, including
      one case with grade 4 toxicity), liver enzyme elevation (10.4%), fatigue (6.3%),
      and hypertension (6.3%). Median PFS was 3.7 months for pazopanib maintenance and
      1.8 months for placebo (hazard ratio 0.44, 95% confidence interval: 0.29-0.69,
      P<0.0001). CONCLUSIONS: Pazopanib maintenance significantly prolonged PFS in
      patients with ED-SCLC. Given the toxicity profiles, however, relevant biomarkers
      to select patients for benefit from pazopanib should be further investigated.

PMID- 29381691
TI  - MGA, L3MBTL2 and E2F6 determine genomic binding of the non-canonical Polycomb
      repressive complex PRC1.6.
AB  - Diverse Polycomb repressive complexes 1 (PRC1) play essential roles in gene
      regulation, differentiation and development. Six major groups of PRC1 complexes
      that differ in their subunit composition have been identified in mammals. How the
      different PRC1 complexes are recruited to specific genomic sites is poorly
      understood. The Polycomb Ring finger protein PCGF6, the transcription factors MGA
      and E2F6, and the histone-binding protein L3MBTL2 are specific components of the
      non-canonical PRC1.6 complex. In this study, we have investigated their role in
      genomic targeting of PRC1.6. ChIP-seq analysis revealed colocalization of MGA,
      L3MBTL2, E2F6 and PCGF6 genome-wide. Ablation of MGA in a human cell line by
      CRISPR/Cas resulted in complete loss of PRC1.6 binding. Rescue experiments
      revealed that MGA recruits PRC1.6 to specific loci both by DNA binding-dependent
      and by DNA binding-independent mechanisms. Depletion of L3MBTL2 and E2F6 but not
      of PCGF6 resulted in differential, locus-specific loss of PRC1.6 binding
      illustrating that different subunits mediate PRC1.6 loading to distinct sets of
      promoters. Mga, L3mbtl2 and Pcgf6 colocalize also in mouse embryonic stem cells,
      where PRC1.6 has been linked to repression of germ cell-related genes. Our
      findings unveil strikingly different genomic recruitment mechanisms of the non
      canonical PRC1.6 complex, which specify its cell type- and context-specific
      regulatory functions.

PMID- 29381692
TI  - Rhinoscleroma pathogenesis: The type K3 capsule of Klebsiella rhinoscleromatis is
      a virulence factor not involved in Mikulicz cells formation.
AB  - Rhinoscleroma is a human specific chronic granulomatous infection of the nose and
      upper airways caused by the Gram-negative bacterium Klebsiella pneumoniae subsp.
      rhinoscleromatis. Although considered a rare disease, it is endemic in low-income
      countries where hygienic conditions are poor. A hallmark of this pathology is the
      appearance of atypical foamy monocytes called Mikulicz cells. However, the
      pathogenesis of rhinoscleroma remains poorly investigated. Capsule polysaccharide
      (CPS) is a prominent virulence factor in bacteria. All K. rhinoscleromatis
      strains are of K3 serotype, suggesting that CPS can be an important driver of
      rhinoscleroma disease. In this study, we describe the creation of the first
      mutant of K. rhinoscleromatis, inactivated in its capsule export machinery. Using
      a murine model recapitulating the formation of Mikulicz cells in lungs, we
      observed that a K. rhinoscleromatis CPS mutant (KR cps-) is strongly attenuated
      and that mice infected with a high dose of KR cps- are still able to induce
      Mikulicz cells formation, unlike a K. pneumoniae capsule mutant, and to partially
      recapitulate the characteristic strong production of IL-10. Altogether, the
      results of this study show that CPS is a virulence factor of K. rhinoscleromatis
      not involved in the specific appearance of Mikulicz cells.

PMID- 29381693
TI  - Metabolic plasticity in synthetic lethal mutants: Viability at higher cost.
AB  - The most frequent form of pairwise synthetic lethality (SL) in metabolic networks
      is known as plasticity synthetic lethality. It occurs when the simultaneous
      inhibition of paired functional and silent metabolic reactions or genes is
      lethal, while the default of the functional partner is backed up by the
      activation of the silent one. Using computational techniques on bacterial genome
      scale metabolic reconstructions, we found that the failure of the functional
      partner triggers a critical reorganization of fluxes to ensure viability in the
      mutant which not only affects the SL pair but a significant fraction of other
      interconnected reactions, forming what we call a SL cluster. Interestingly, SL
      clusters show a strong entanglement both in terms of reactions and genes. This
      strong overlap mitigates the acquired vulnerabilities and increased structural
      and functional costs that pay for the robustness provided by essential
      plasticity. Finally, the participation of coessential reactions and genes in
      different SL clusters is very heterogeneous and those at the intersection of many
      SL clusters could serve as supertargets for more efficient drug action in the
      treatment of complex diseases and to elucidate improved strategies directed to
      reduce undesired resistance to chemicals in pathogens.

PMID- 29381694
TI  - Inference of genetic marker concentrations from field surveys to detect
      environmental DNA using Bayesian updating.
AB  - Field studies to detect environmental DNA (eDNA) can be undertaken to infer the
      presence of a rare or cryptic species in a water body. These studies are
      implemented by collecting water samples from the water body, processing those
      samples to isolate genetic material contained in the water sample, and using a
      laboratory assay to find a species-specific genetic marker within a sample of the
      genetic material. To date, conventional polymerase chain reaction (PCR) has been
      one of the most widely used assays in field studies to detect eDNA. This assay is
      strictly a test for the presence of the genetic marker. It provides no estimate
      of the concentration of the target genetic marker in the sample or in the
      environment. Understanding the concentration of a target marker in the
      environment is a critical first step toward using the results of eDNA field
      surveys to support inferences about the location and strength of eDNA sources. In
      this study, the results of eDNA field surveys are combined with a model of the
      sensitivity of the field survey methods to estimate target marker concentrations
      using Bayesian updating. The method is demonstrated for Asian carp in the Chicago
      Area Waterway System (CAWS) using the results of field surveys for eDNA carried
      out during the period 2009 through 2012, a four-year period during which more
      than 5,800 two-liter water samples were collected and analyzed using PCR.
      Concentrations of bighead carp (Hypophthalmichthys nobilis) and silver carp
      (Hypophthalmichthys molitrix) eDNA are estimated for twenty hydrologic reaches of
      the CAWS. This study also assesses the sensitivity of these concentration
      estimates to evidentiary criteria that limit what evidence is used in Bayesian
      updating based on requirements for sampling intensity and frequency.

PMID- 29381695
TI  - What's coming for health science and policy in 2018? Global experts look ahead in
      their field.
AB  - In PLOS Medicine's first editorial of 2018, editorial board members and other
      leading researchers share their hopes, pleas, concerns, and expectations for this
      year in health research and policy.

PMID- 29381696
TI  - Association between triglyceride levels and cardiovascular disease in patients
      with acute pancreatitis.
AB  - Conventional wisdom supports prescribing "fibrates before statins", that is,
      prioritizing treatment of hypertriglyceridemia (hTG) to prevent pancreatitis
      ahead of low-density lipoprotein cholesterol to prevent coronary heart disease.
      The relationship between hTG and acute pancreatitis, however, may not support
      this approach to clinical management. This study analyzed administrative data
      from the Veterans Health Administration for evidence of (1) temporal association
      between assessed triglycerides level and days to acute pancreatitis admission;
      (2) association between hTG and outcomes in the year after hospitalization for
      acute pancreatitis; (3) relative rates of prescription of fibrates vs statins in
      patients with acute pancreatitis; (4) association of prescription of fibrates
      alone versus fibrates with statins or statins alone with rates of adverse
      outcomes after hospitalization for acute pancreatitis. Only modest association
      was found between above-normal or extremely high triglycerides and time until
      acute pancreatitis. CHD/MI/stroke occurred in 23% in the year following AP,
      supporting cardiovascular risk management. Fibrates were prescribed less often
      than statins, defying conventional wisdom, but the high rates of cardiovascular
      events in the year following AP support a clinical focus on reducing
      cardiovascular risk factors.

PMID- 29381697
TI  - Policy responses to hepatitis C in the Nordic countries: Gaps and discrepant
      reporting in the Hep-Nordic study.
AB  - BACKGROUND AND AIMS: In the Nordic countries (Denmark, Finland, Iceland, Norway,
      Sweden), the prevalence of chronic hepatitis C virus (HCV) infection is
      relatively low in the general population, but is much higher among people who
      inject drugs (PWID). We conducted an exploratory study to investigate the extent
      to which these countries have policies supporting key elements of the public
      health response that is necessary to achieve the global goal of eliminating HCV
      as a public health threat. METHODS: Fourteen stakeholders representing government
      agencies, medical societies, and civil society organisations (CSOs) in the Nordic
      countries completed a cross-sectional online survey that included 21 policy
      questions related to national coordination, prevention, testing, linkage to care,
      and treatment. We summarised the findings in a descriptive analysis, and noted
      discrepant responses from stakeholders within the same country. RESULTS:
      Stakeholders reported that three of the five study countries have national viral
      hepatitis strategies, while only Iceland has a national HCV elimination goal. The
      availability of harm reduction services varies, with opioid substitution therapy
      provided for the general population throughout all countries, but not needle and
      syringe programmes. No country has access to anonymous HCV testing in all parts
      of the country. National HCV treatment guidelines are available in all countries
      except Finland, and all countries provide publicly funded direct-acting antiviral
      treatment. Disagreement regarding policies was observed across countries, and
      CSOs were the stakeholder group that most frequently answered survey questions
      incorrectly. CONCLUSION: The Nordic region as a whole has not consistently
      expressed its commitment to tackling HCV, despite the existence of large HCV
      epidemics among PWID in these countries. Stakeholder alignment and an established
      elimination goal with an accompanying strategy and implementation plan should be
      recognised as the basis for coordinated national public health efforts to achieve
      HCV elimination in the Nordic region and elsewhere.

PMID- 29381698
TI  - Role of the AP-5 adaptor protein complex in late endosome-to-Golgi retrieval.
AB  - The AP-5 adaptor protein complex is presumed to function in membrane traffic, but
      so far nothing is known about its pathway or its cargo. We have used CRISPR-Cas9
      to knock out the AP-5 zeta subunit gene, AP5Z1, in HeLa cells, and then analysed
      the phenotype by subcellular fractionation profiling and quantitative mass
      spectrometry. The retromer complex had an altered steady-state distribution in
      the knockout cells, and several Golgi proteins, including GOLIM4 and GOLM1, were
      depleted from vesicle-enriched fractions. Immunolocalisation showed that loss of
      AP-5 led to impaired retrieval of the cation-independent mannose 6-phosphate
      receptor (CIMPR), GOLIM4, and GOLM1 from endosomes back to the Golgi region.
      Knocking down the retromer complex exacerbated this phenotype. Both the CIMPR and
      sortilin interacted with the AP-5-associated protein SPG15 in pull-down assays,
      and we propose that sortilin may act as a link between Golgi proteins and the AP
      5/SPG11/SPG15 complex. Together, our findings suggest that AP-5 functions in a
      novel sorting step out of late endosomes, acting as a backup pathway for
      retromer. This provides a mechanistic explanation for why mutations in AP
      5/SPG11/SPG15 cause cells to accumulate aberrant endolysosomes, and highlights
      the role of endosome/lysosome dysfunction in the pathology of hereditary spastic
      paraplegia and other neurodegenerative disorders.

PMID- 29381699
TI  - Novel genetic polymorphisms associated with severe malaria and under selective
      pressure in North-eastern Tanzania.
AB  - Significant selection pressure has been exerted on the genomes of human
      populations exposed to Plasmodium falciparum infection, resulting in the
      acquisition of mechanisms of resistance against severe malarial disease. Many
      host genetic factors, including sickle cell trait, have been associated with
      reduced risk of developing severe malaria, but do not account for all of the
      observed phenotypic variation. Identification of novel inherited risk factors
      relies upon high-resolution genome-wide association studies (GWAS). We present
      findings of a GWAS of severe malaria performed in a Tanzanian population (n =
      914, 15.2 million SNPs). Beyond the expected association with the sickle cell HbS
      variant, we identify protective associations within two interleukin receptors (IL
      23R and IL-12RBR2) and the kelch-like protein KLHL3 (all P<10-6), as well as near
      significant effects for Major Histocompatibility Complex (MHC) haplotypes.
      Complementary analyses, based on detecting extended haplotype homozygosity,
      identified SYNJ2BP, GCLC and MHC as potential loci under recent positive
      selection. Through whole genome sequencing of an independent Tanzanian cohort
      (parent-child trios n = 247), we confirm the allele frequencies of common
      polymorphisms underlying associations and selection, as well as the presence of
      multiple structural variants that could be in linkage with these SNPs. Imputation
      of structural variants in a region encompassing the glycophorin genes on
      chromosome 4, led to the characterisation of more than 50 rare variants, and
      individually no strong evidence of associations with severe malaria in our
      primary dataset (P>0.3). Our approach demonstrates the potential of a joint
      genotyping-sequencing strategy to identify as-yet unknown susceptibility loci in
      an African population with well-characterised malaria phenotypes. The regions
      encompassing these loci are potential targets for the design of much needed
      interventions for preventing or treating malarial disease.

PMID- 29381700
TI  - Ecosystem-based fisheries management: Perception on definitions, implementations,
      and aspirations.
AB  - Ecosystem-based fisheries management (EBFM) was developed to move beyond single
      species management by incorporating ecosystem considerations for the sustainable
      utilization of marine resources. Due to the wide range of fishery
      characteristics, including different goals of fisheries management across regions
      and species, theoretical best practices for EBFM vary greatly. Here we highlight
      the lack of consensus in the interpretation of EBFM amongst professionals in
      marine science and its implementation. Fisheries policy-makers and managers,
      stock assessment scientists, conservationists, and ecologists had very different
      opinions on the degree to which certain management strategies would be considered
      EBFM. We then assess the variability of the implementation of EBFM, where we
      created a checklist of characteristics typifying EBFM and scored fisheries across
      different regions, species, ecosystems, and fishery size and capacity. Our
      assessments show fisheries are unlikely to meet all the criteria on the EBFM
      checklist. Consequentially, it is unnecessary for management to practice all the
      traits of EBFM, as some may be disparate from the ecosystem attributes or fishery
      goals. Instead, incorporating some ecosystem-based considerations to fisheries
      management that are context-specific is a more realistic and useful way for EBFM
      to occur in practice.

PMID- 29381701
TI  - The ratio between cerebral blood flow and Tmax predicts the quality of
      collaterals in acute ischemic stroke.
AB  - BACKGROUND: In acute ischemic stroke the status of collateral circulation is a
      critical factor in determining outcome. We propose a less invasive alternative to
      digital subtraction angiography for evaluating collaterals based on dynamic
      susceptibility contrast magnetic resonance imaging. METHODS: Perfusion maps of
      Tmax and cerebral blood flow (CBF) were created for 35 patients with baseline
      occlusion of a major cerebral artery. Volumes of hypoperfusion were defined as
      having a Tmax delay of > 4 seconds (Tmax4s) and > 6 seconds (Tmax6s) and a CBF
      drop below 80% of healthy, contralateral tissue. For each patient a ratio between
      the volume of the CBF and the Tmax based perfusion deficit was calculated.
      Associations with collateral status and radiological outcome were assessed with
      the Mann-Whitney-U test, uni- and multivariable logistic regression analyses as
      well as area under the receiver-operator-characteristic (ROC) curve. RESULTS: The
      CBF/Tmax volume ratios were significantly associated with bad collateral status
      in crude logistic regression analysis as well as with adjustment for NIHSS at
      admission and baseline infarct volume (OR = 2.5 95% CI[1.2-5.4] p = 0.020 for
      CBF/Tmax 4s volume ratio and OR = 1.6 95% CI[1.0-2.6] p = 0.031 for CBF/Tmax6s
      volume ratio). Moreover, the ratios were significantly correlated to final
      infarct size (Spearman's rho = 0.711 and 0.619, respectively for the CBF/Tmax4s
      volume ratio and CBF/Tmax6s volume ration, all p<0.001). The ratios also had a
      high area under the ROC curve of 0.93 95%CI[0.86-1.00]) and 0.90 95%CI[0.80
      1.00]respectively for predicting poor radiological outcome. CONCLUSIONS: In the
      setting of acute ischemic stroke the CBF/Tmax volume ratio can be used to
      differentiate between good and insufficient collateral circulation without the
      need for invasive procedures like conventional angiography.

PMID- 29381703
TI  - SozRank: A new approach for localizing the epileptic seizure onset zone.
AB  - Epilepsy is one of the most common neurological disorders affecting about 1% of
      the world population. For patients with focal seizures that cannot be treated
      with antiepileptic drugs, the common treatment is a surgical procedure for
      removal of the seizure onset zone (SOZ). In this work we introduce an algorithm
      for automatic localization of the seizure onset zone (SOZ) in epileptic patients
      based on electrocorticography (ECoG) recordings. The proposed algorithm builds
      upon the hypothesis that the abnormal excessive (or synchronous) neuronal
      activity in the brain leading to seizures starts in the SOZ and then spreads to
      other areas in the brain. Thus, when this abnormal activity starts, signals
      recorded at electrodes close to the SOZ should have a relatively large causal
      influence on the rest of the recorded signals. The SOZ localization is executed
      in two steps. First, the algorithm represents the set of electrodes using a
      directed graph in which nodes correspond to recording electrodes and the edges'
      weights quantify the pair-wise causal influence between the recorded signals.
      Then, the algorithm infers the SOZ from the estimated graph using a variant of
      the PageRank algorithm followed by a novel post-processing phase. Inference
      results for 19 patients show a close match between the SOZ inferred by the
      proposed approach and the SOZ estimated by expert neurologists (success rate of
      17 out of 19).

PMID- 29381702
TI  - Long-term trends in mortality and AIDS-defining events after combination ART
      initiation among children and adolescents with perinatal HIV infection in 17
      middle- and high-income countries in Europe and Thailand: A cohort study.
AB  - BACKGROUND: Published estimates of mortality and progression to AIDS as children
      with HIV approach adulthood are limited. We describe rates and risk factors for
      death and AIDS-defining events in children and adolescents after initiation of
      combination antiretroviral therapy (cART) in 17 middle- and high-income
      countries, including some in Western and Central Europe (W&CE), Eastern Europe
      (Russia and Ukraine), and Thailand. METHODS AND FINDINGS: Children with perinatal
      HIV aged <18 years initiating cART were followed until their 21st birthday,
      transfer to adult care, death, loss to follow-up, or last visit up until 31
      December 2013. Rates of death and first AIDS-defining events were calculated.
      Baseline and time-updated risk factors for early/late (<=/>6 months of cART)
      death and progression to AIDS were assessed. Of 3,526 children included, 32% were
      from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia
      or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR
      1.4-9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage
      <15% in 1997-2003, which fell to 15% of children in 2011 onwards (p < 0.001).
      Similarly, 53% and 18% of children >=5 years had a CD4 count <200 cells/mm3 in
      1997-2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6
      (2.9-8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and
      100 (42%) were within 6 months of initiating cART, respectively. Multivariable
      predictors of early death were: being in the first year of life; residence in
      Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe
      immune suppression; and low BMI-for-age z-score. Current severe immune
      suppression, low current BMI-for-age z-score, and current viral load >400 c/mL
      predicted late death. Predictors of early and late progression to AIDS were
      similar. Study limitations include incomplete recording of US Centers for Disease
      Control (CDC) disease stage B events and serious adverse events in some
      countries; events that were distributed over a long time period, and that we
      lacked power to analyse trends in patterns and causes of death over time.
      CONCLUSIONS: In our study, 3,526 children and adolescents with perinatal HIV
      infection initiated antiretroviral therapy (ART) in countries in Europe and
      Thailand. We observed that over 40% of deaths occurred <=6 months after cART
      initiation. Greater early mortality risk in infants, as compared to older
      children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises
      concern. Current severe immune suppression, being underweight, and unsuppressed
      viral load were associated with a higher risk of death at >6 months after
      initiation of cART.

PMID- 29381704
TI  - Traumatic brain injury and the risk of dementia diagnosis: A nationwide cohort
      study.
AB  - BACKGROUND: Traumatic brain injury (TBI) has been associated with dementia. The
      questions of whether the risk of dementia decreases over time after TBI, whether
      it is similar for different TBI types, and whether it is influenced by familial
      aggregation are not well studied. METHODS AND FINDINGS: The cohort considered for
      inclusion comprised all individuals in Sweden aged >=50 years on December 31,
      2005 (n = 3,329,360). Diagnoses of dementia and TBI were tracked through
      nationwide databases from 1964 until December 31, 2012. In a first cohort,
      individuals diagnosed with TBI (n = 164,334) were matched with up to two
      controls. A second cohort consisted of subjects diagnosed with dementia during
      follow-up (n = 136,233) matched with up to two controls. A third cohort consisted
      of 46,970 full sibling pairs with discordant TBI status. During a mean follow-up
      period of 15.3 (range, 0-49) years, 21,963 individuals in the first cohort (6.3%
      with TBI, 3.6% without TBI) were diagnosed with dementia (adjusted odds ratio
      [OR], 1.81; 95% confidence interval [CI], 1.75-1.86). The association was
      strongest in the first year after TBI (OR, 3.52; 95% CI, 3.23-3.84), but the risk
      remained significant >30 years (OR, 1.25; 95% CI, 1.11-1.41). Single mild TBI
      showed a weaker association with dementia (OR, 1.63; 95% CI, 1.57-1.70) than did
      more severe TBI (OR, 2.06; 95% CI, 1.95-2.19) and multiple TBIs (OR, 2.81; 95%
      CI, 2.51-3.15). These results were in general confirmed in the nested case
      control cohort. TBI was also associated with an increased risk of dementia
      diagnosis in sibling pairs with discordant TBI status (OR, 1.89; 95% CI, 1.62
      2.21). A main limitation of the present study is the observational design. Thus,
      no causal inferences can be made based on the associations found. CONCLUSIONS:
      The risk of dementia diagnosis decreased over time after TBI, but it was still
      evident >30 years after the trauma. The association was stronger for more severe
      TBI and multiple TBIs, and it persisted after adjustment for familial factors.

PMID- 29381705
TI  - Prediction of reaction knockouts to maximize succinate production by
      Actinobacillus succinogenes.
AB  - Succinate is a precursor of multiple commodity chemicals and bio-based succinate
      production is an active area of industrial bioengineering research. One of the
      most important microbial strains for bio-based production of succinate is the
      capnophilic gram-negative bacterium Actinobacillus succinogenes, which naturally
      produces succinate by a mixed-acid fermentative pathway. To engineer A.
      succinogenes to improve succinate yields during mixed acid fermentation, it is
      important to have a detailed understanding of the metabolic flux distribution in
      A. succinogenes when grown in suitable media. To this end, we have developed a
      detailed stoichiometric model of the A. succinogenes central metabolism that
      includes the biosynthetic pathways for the main components of biomass-namely
      glycogen, amino acids, DNA, RNA, lipids and UDP-N-Acetyl-alpha-D-glucosamine. We
      have validated our model by comparing model predictions generated via flux
      balance analysis with experimental results on mixed acid fermentation. Moreover,
      we have used the model to predict single and double reaction knockouts to
      maximize succinate production while maintaining growth viability. According to
      our model, succinate production can be maximized by knocking out either of the
      reactions catalyzed by the PTA (phosphate acetyltransferase) and ACK (acetyl
      kinase) enzymes, whereas the double knockouts of PEPCK (phosphoenolpyruvate
      carboxykinase) and PTA or PEPCK and ACK enzymes are the most effective in
      increasing succinate production.

PMID- 29381707
TI  - Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity
      by a Rap1-dependent mechanism.
AB  - Rasa3 is a GTPase activating protein of the GAP1 family which targets R-Ras and
      Rap1. Although catalytic inactivation or deletion of Rasa3 in mice leads to
      severe hemorrhages and embryonic lethality, the biological function and cellular
      location of Rasa3 underlying these defects remains unknown. Here, using a
      combination of loss of function studies in mouse and zebrafish as well as in
      vitro cell biology approaches, we identify a key role for Rasa3 in endothelial
      cells and vascular lumen integrity. Specific ablation of Rasa3 in the mouse
      endothelium, but not in megakaryocytes and platelets, lead to embryonic bleeding
      and death at mid-gestation, recapitulating the phenotype observed in full Rasa3
      knock-out mice. Reduced plexus/sprouts formation and vascular lumenization
      defects were observed when Rasa3 was specifically inactivated in mouse
      endothelial cells at the postnatal or adult stages. Similar results were obtained
      in zebrafish after decreasing Rasa3 expression. In vitro, depletion of Rasa3 in
      cultured endothelial cells increased beta1 integrin activation and cell adhesion
      to extracellular matrix components, decreased cell migration and blocked
      tubulogenesis. During migration, these Rasa3-depleted cells exhibited larger and
      more mature adhesions resulting from a perturbed dynamics of adhesion assembly
      and disassembly which significantly increased their life time. These defects were
      due to a hyperactivation of the Rap1 GTPase and blockade of FAK/Src signaling.
      Finally, Rasa3-depleted cells showed reduced turnover of VE-cadherin-based
      adhesions resulting in more stable endothelial cell-cell adhesion and decreased
      endothelial permeability. Altogether, our results indicate that Rasa3 is a
      critical regulator of Rap1 in endothelial cells which controls adhesions
      properties and vascular lumen integrity; its specific endothelial cell
      inactivation results in occluded blood vessels, hemorrhages and early embryonic
      death in mouse, mimicking thus the Rasa3-/- mouse phenotype.

PMID- 29381706
TI  - Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika
      virus infection.
AB  - Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy
      outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate
      in the first trimester. The pregnancy was complicated by preterm premature
      rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise
      49 days post infection (gestational day 95). Significant pathology at the
      maternal-fetal interface included acute chorioamnionitis, placental infarcts, and
      leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was
      disseminated throughout fetal tissues and maternal immune system tissues at
      necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was
      identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent
      in situ hybridization for viral replication intermediates. Fetal ocular pathology
      included a choroidal coloboma, suspected anterior segment dysgenesis, and a
      dysplastic retina. This is the first report of ocular pathology and prolonged
      viral replication in both maternal and fetal tissues following congenital ZIKV
      infection in a rhesus macaque. PPROM followed by fetal demise and severe
      pathology of the visual system have not been described in macaque congenital ZIKV
      infection previously. While this case of ZIKV infection during pregnancy was
      complicated by bacterial infection with PPROM, the role of ZIKV on this outcome
      cannot be precisely defined, and further nonhuman primate studies will determine
      if increased risk for PPROM or other adverse pregnancy outcomes are associated
      with congenital ZIKV infection.

PMID- 29381708
TI  - RNA-seq transcriptome analysis of the immature seeds of two Brassica napus lines
      with extremely different thousand-seed weight to identify the candidate genes
      related to seed weight.
AB  - Brassica napus is an important oilseed crop worldwide. Although seed weight is
      the main determinant of seed yield, few studies have focused on the molecular
      mechanisms that regulate seed weight in B. napus. In this study, the immature
      seeds of G-42 and 7-9, two B. napus doubled haploid (DH) lines with extremely
      different thousand-seed weight (TSW), were selected for a transcriptome analysis
      to determine the regulatory mechanisms underlying seed weight at the whole gene
      expression level and to identify candidate genes related to seed weight. A total
      of 2,251 new genes and 2,205 differentially expressed genes (DEGs) were obtained
      via RNA-seq (RNA sequencing). Among these genes, 1,747 (77.61%) new genes and
      2020 (91.61%) DEGs were successfully annotated. Of these DEGs, 1,118 were up
      regulated and 1,087 were down-regulated in the large-seed line. The Kyoto
      Encyclopedia of Genes and Genomes (KEGG) database analysis indicated that 15 DEGs
      were involved in ubiquitin-mediated proteolysis and proteasome pathways, which
      might participate in regulating seed weight. The Gene Ontology (GO) database
      indicated that 222 DEGs were associated with the biological process or molecular
      function categories related to seed weight, such as cell division, cell size and
      cell cycle regulation, seed development, nutrient reservoir activity, and
      proteasome-mediated ubiquitin-dependent protein catabolic processes. Moreover, 50
      DEGs encoding key enzymes or proteins were identified that likely participate in
      regulating seed weight. A DEG (GSBRNA2T00037121001) identified by the
      transcriptome analysis was also previously identified in a quantitative trait
      locus (QTL) region for seed weight via SLAF-seq (Specific Locus Amplified
      Fragment sequencing). Finally, the expression of 10 DEGs with putative roles in
      seed weight and the expression of the DEG GSBRNA2T00037121001 were confirmed by a
      quantitative real-time reverse transcription PCR (qRT-PCR) analysis, and the
      results were consistent with the RNA sequencing data. This work has provided new
      insights on the molecular mechanisms underlying seed weight-related biosynthesis
      and has laid a solid foundation for further improvements to the seed yield of oil
      crops.

PMID- 29381709
TI  - Dynamic magnetic resonance imaging method based on golden-ratio cartesian
      sampling and compressed sensing.
AB  - Dynamic magnetic resonance imaging (DMRI) is used to noninvasively trace the
      movements of organs and the process of drug delivery. The results can provide
      quantitative or semiquantitative pathology-related parameters, thus giving DMRI
      great potential for clinical applications. However, conventional DMRI techniques
      suffer from low temporal resolution and long scan time owing to the limitations
      of the k-space sampling scheme and image reconstruction algorithm. In this paper,
      we propose a novel DMRI sampling scheme based on a golden-ratio Cartesian
      trajectory in combination with a compressed sensing reconstruction algorithm. The
      results of two simulation experiments, designed according to the two major DMRI
      techniques, showed that the proposed method can improve the temporal resolution
      and shorten the scan time and provide high-quality reconstructed images.

PMID- 29381710
TI  - Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09
      virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1
      challenge in the growing pig model.
AB  - Swine influenza A viruses (IAV-S) found in North American pigs are diverse and
      the lack of cross-protection among heterologous strains is a concern. The
      objective of this study was to compare a commercial inactivated A/H1N1/pdm09
      (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e)
      epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative
      pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again
      at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit
      particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine
      (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine
      (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or
      sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the
      time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV
      nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1
      hemagglutination inhibition (HI) titers compared to all other groups, and M2e
      specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e
      pigs with significantly higher group means in the NvComplex/M2e group compared to
      SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly
      reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this
      group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were
      characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple
      consolidated areas typical of IAV infection and were similar for NvParticle/M2e,
      NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the
      SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a
      commercial Inact/pH1N1 specific vaccine effectively protected pigs against
      homologous challenge as evidenced by reduced clinical signs, virus shedding in
      nasal secretions and oral fluids and reduced macroscopic and microscopic lesions
      whereas intranasal vaccination with experimental M2e epitope-based subunit
      vaccines did not. The results further highlight the importance using IAV-S type
      specific vaccines in pigs.

PMID- 29381711
TI  - Validation of the Perceived Stigmatization Questionnaire for Brazilian adult burn
      patients.
AB  - Currently, there is no questionnaire to assess perceived stigmatization among
      people with visible differences in Brazil. The Perceived Stigmatization
      Questionnaire (PSQ), developed in the United States, is a valid instrument to
      assess the perception of stigmatizing behaviours among burn survivors. The
      objective of this cross-sectional and multicentre study was to assess the factor
      structure, reliability and validity of the Brazilian Portuguese version of the
      PSQ in burn patients. A Brazilian version of the 21-item PSQ was answered by 240
      adult burn patients, undergoing rehabilitation in two burns units in Brazil. We
      tested its construct validity by correlating PSQ scores with depression (Beck
      Depression Index-BDI) and self-esteem (Rosenberg Self-Esteem Scale-RSE), as well
      as with two domains of the Revised Burn Specific Health Scale-BSHS-R: affect and
      body image, and interpersonal relationships. We used Confirmatory Item Factor
      Analysis (CIFA) to test whether the data fit a measurement model involving a
      three-factor structure (absence of friendly behaviour; confusing/staring
      behaviour; and hostile behaviour). We conducted Exploratory Factor Analyses (EFA)
      of the subscale in a 50% random sample of individuals (training split), treating
      items as ordinal categorical using unweighted least squares estimation. To assess
      discriminant validity of the Brazilian version of the PSQ we correlated PSQ
      scores with known groups (sex, total body surface area burned, and visibility of
      the scars) and assessed its reliability by means of Cronbach's alpha and using
      test-retest. Goodness-of-fit indices for confirmatory factor analysis were
      satisfactory for the PSQ, but not for the hostile behaviour subscale, which was
      modified to improve fit by eliminating 3 items. Cronbach's alphas for the PSQ
      refined version (PSQ-R) ranged from 0.65 to 0.88, with test-retest reliability
      0.87 for the total score. The PSQ-R scores correlated strongly with depression
      (0.63; p < 0.001), self-esteem (-0.57; p < 0.001), body image (-0.63; p < 0.001),
      and interpersonal relationships (-0.55; p < 0.001). PSQ-R total scores were
      significantly lower for patients with visible scars (effect size = 0.51, p =
      0.029). The PSQ-R showed reliability and validity comparable to the original
      version. However, the cross-cultural structure of the subscale "hostile
      behaviour" and sensitivity to change of the PSQ should be further evaluated.

PMID- 29381712
TI  - Plant growth and fertility requires functional interactions between specific PABP
      and eIF4G gene family members.
AB  - The initiation of protein synthesis requires the involvement of the eukaryotic
      translation initiation factor (eIF) 4G to promote assembly of the factors needed
      to recruit a 40S ribosomal subunit to an mRNA. Although many eukaryotes express
      two eIF4G isoforms that are highly similar, those in plants, referred to as eIF4G
      and eIFiso4G, are highly divergent in size, sequence, and domain organization.
      Species of the Brassicaceae and the Cleomaceae also express a divergent eIFiso4G
      isoform, referred to as eIFiso4G2, not found elsewhere in the plant kingdom.
      Despite their divergence, eIF4G and eIFiso4G interact with eIF4A, eIF4B, and
      eIF4E isoforms needed for binding an mRNA. eIF4G and eIFiso4G also interact with
      the poly(A)-binding protein (PABP) which promotes ribosome recruitment to an
      mRNA. Increasing the complexity of such an interaction, however, Arabidopsis also
      expresses three PABP isoforms (PAB2, PAB4, and PAB8) in vegetative and
      reproductive tissues. In this study, the functional interactions among the eIF4G
      and the widely-expressed PABP isoforms were examined. Loss of PAB2 or PAB8 in
      combination with loss of eIF4G or eIFiso4G had little to no effect on growth or
      fertility whereas pab2 pab8 eif4g or pab2 pab8 eifiso4g1/2 mutants exhibited
      smaller stature and reduced fertility. Although the pab4 eifiso4g1 mutant grows
      normally and is fertile, pab4 eif4g or pab4 eifiso4g2 mutants could not be
      isolated. Even pab4/PAB4 eif4g/eIF4G heterozygous plants exhibited growth defects
      and low fertility. Mutant co-inheritance analysis in reciprocal crosses with wild
      type plants revealed that most ovaries and pollen from pab4/PAB4 eif4g/eIF4G
      plants were PAB4 eif4g. Similarly, co-inheritance studies with pab4/PAB4
      eifiso4g2/eIFiso4G2 plants suggested most ovaries were PAB4 eifiso4g2. These
      results suggest that a functional interaction between PAB4 and eIF4G and between
      PAB4 and eIFiso4G2 is required for growth and normal fertility.

PMID- 29381713
TI  - Effect of light wavelength on hot spring microbial mat biodiversity.
AB  - Hot spring associated phototrophic microbial mats are purely microbial
      communities, in which phototrophic bacteria function as primary producers and
      thus shape the community. The microbial mats at Nakabusa hot springs in Japan
      harbor diverse photosynthetic bacteria, mainly Thermosynechococcus, Chloroflexus,
      and Roseiflexus, which use light of different wavelength for energy conversion.
      The aim of this study was to investigate the effect of the phototrophs on
      biodiversity and community composition in hot spring microbial mats. For this, we
      specifically activated the different phototrophs by irradiating the mats with
      different wavelengths in situ. We used 625, 730, and 890 nm wavelength LEDs alone
      or in combination and confirmed the hypothesized increase in relative abundance
      of different phototrophs by 16S rRNA gene sequencing. In addition to the increase
      of the targeted phototrophs, we studied the effect of the different treatments on
      chemotrophic members. The specific activation of Thermosynechococcus led to
      increased abundance of several other bacteria, whereas wavelengths specific to
      Chloroflexus and Roseiflexus induced a decrease in >50% of the community members
      as compared to the dark conditions. This suggests that the growth of
      Thermosynechococcus at the surface layer benefits many community members, whereas
      less benefit is obtained from an increase in filamentous anoxygenic phototrophs
      Chloroflexus and Roseiflexus. The increases in relative abundance of chemotrophs
      under different light conditions suggest a relationship between the two groups.
      Aerobic chemoheterotrophs such as Thermus sp. and Meiothermus sp. are thought to
      benefit from aerobic conditions and organic carbon in the form of photosynthates
      by Thermosynechococcus, while the oxidation of sulfide and production of
      elemental sulfur by filamentous anoxygenic phototrophs benefit the sulfur
      disproportionating Caldimicrobium thiodismutans. In this study, we used an
      experimental approach under controlled environmental conditions for the analysis
      of natural microbial communities, which proved to be a powerful tool to study
      interspecies relationships in the microbiome.

PMID- 29381714
TI  - Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and
      Acinetobacter baumannii among horses entering a veterinary teaching hospital: The
      contemporary "Trojan Horse".
AB  - Pathogens frequently associated with multi-drug resistant (MDR) phenotypes,
      including extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
      (ESBL-E) and Acinetobacter baumannii isolated from horses admitted to horse
      clinics, pose a risk for animal patients and personnel in horse clinics. To
      estimate current rates of colonization, a total of 341 equine patients were
      screened for carriage of zoonotic indicator pathogens at hospital admission.
      Horses showing clinical signs associated with colic (n = 233) or open wounds (n =
      108) were selected for microbiological examination of nostril swabs, faecal
      samples and wound swabs taken from the open wound group. The results showed
      alarming carriage rates of Gram-negative MDR pathogens in equine patients: 10.7%
      (34 of 318) of validated faecal specimens were positive for ESBL-E (94%: ESBL
      producing Escherichia coli), with recorded rates of 10.5% for the colic and 11%
      for the open wound group. 92.7% of the ESBL-producing E. coli were phenotypically
      resistant to three or more classes of antimicrobials. A. baumannii was rarely
      detected (0.9%), and all faecal samples investigated were negative for
      Salmonella, both directly and after two enrichment steps. Screening results for
      the equine nostril swabs showed detection rates for ESBL-E of 3.4% among colic
      patients and 0.9% in the open wound group, with an average rate of 2.6% (9/340)
      for both indications. For all 41 ESBL-producing E. coli isolated, a broad
      heterogeneity was revealed using pulsed-field gel electrophoresis (PFGE) patterns
      and whole genome sequencing (WGS) -analysis. However, a predominance of sequence
      type complex (STC)10 and STC1250 was observed, including several novel STs. The
      most common genes associated with ESBL-production were identified as blaCTX-M-1
      (31/41; 75.6%) and blaSHV-12 (24.4%). The results of this study reveal a
      disturbingly large fraction of multi-drug resistant and ESBL-producing E. coli
      among equine patients, posing a clear threat to established hygiene management
      systems and work-place safety of veterinary staff in horse clinics.

PMID- 29381715
TI  - Enterohemorrhagic Escherichia coli O157 subclade 8b strains in Chiba Prefecture,
      Japan, produced larger amounts of Shiga toxin 2 than strains in subclade 8a and
      other clades.
AB  - Enterohemorrhagic Escherichia coli O157 (O157) strains can be classified into
      clades (one of several phylogenetic groups) by single nucleotide polymorphisms
      (SNPs): these are clade 1, clade 2, clade 3, descendant and ancestral clades 4/5,
      clade 6, clade 7, clade 8, clade 9, and clade 12. Some recent studies showed that
      some O157 strains in clade 8 produced a larger amount of Shiga toxin (Stx) 2 than
      other strains. In this study, 1121 epidemiologically unlinked strains of O157
      isolated in Chiba Prefecture, Japan were classified into clades during 1996-2014.
      Clade 8 strains were further classified into subclade 8a (67 strains) and
      subclade 8b (48 strains) using SNP analysis. In the absence of mitomycin C (MMC),
      subclade 8a strains in this study produced significantly greater amounts of Stx2
      than subclade 8b strains. However, in the presence of MMC, the levels of Stx2
      production in subclade 8b strains were significantly greater than subclade 8a
      strains. On the other hand, a recent study reported that the Stx2 production
      level in O157 strains was determined mainly by the subtypes of Stx2a phage
      (phiStx2_alpha, beta, gamma, delta, epsilon, and zeta). Using O157 strains in
      this study, the Stx2a phages were classified into these subtypes. In this study,
      all strains of subclades 8a and 8b carried phiStx2a_gamma and phiStx2a_delta,
      respectively. Some strains in clade 6 also carried phiStx2a_delta. In the
      presence of MMC, subclade 8b strains produced significantly greater amounts of
      Stx2 than clade 6 strains carrying phiStx2_delta. In this study, we propose that
      Stx2 production in subclade 8b strains in the presence of MMC might be enhanced
      due to genetic factors other than phiStx2_delta.

PMID- 29381716
TI  - Quantitative MRI in early intervertebral disc degeneration: T1rho correlates
      better than T2 and ADC with biomechanics, histology and matrix content.
AB  - INTRODUCTION: Low-back pain (LBP) has been correlated to the presence of
      intervertebral disc (IVD) degeneration on T2-weighted (T2w) MRI. It remains
      challenging, however, to accurately stage degenerative disc disease (DDD) based
      on T2w MRI and measurements of IVD height, particularly for early DDD. Several
      quantitative MRI techniques have been introduced to detect changes in matrix
      composition signifying early DDD. In this study, we correlated quantitative T2,
      T1rho and Apparent Diffusion Coefficient (ADC) values to disc mechanical behavior
      and gold standard early DDD markers in a graded degenerated lumbar IVD caprine
      model, to assess their potential for early DDD detection. METHODS: Lumbar caprine
      IVDs were injected with either 0.25 U/ml or 0.5 U/ml Chondroitinase ABC (Cabc) to
      trigger early DDD-like degeneration. Injection with phosphate-buffered saline
      (PBS) served as control. IVDs were cultured in a bioreactor for 20 days under
      axial physiological loading. High-resolution 9.4 T MR images were obtained prior
      to intervention and after culture. Quantitative MR results were correlated to
      recovery behavior, histological degeneration grading, and the content of
      glycosaminoglycans (GAGs) and water. RESULTS: Cabc-injected IVDs showed
      aberrancies in biomechanics and loss of GAGs without changes in water-content.
      All MR sequences detected changes in matrix composition, with T1rho showing
      largest changes pre-to-post in the nucleus, and significantly more than T2 and
      ADC. Histologically, degeneration due to Cabc injection was mild. T1rho nucleus
      values correlated strongest with altered biomechanics, histological degeneration
      score, and loss of GAGs. CONCLUSIONS: T2- and T1rho quantitative MR-mapping
      detected early DDD changes. T1rho nucleus values correlated better than T2 and
      ADC with biomechanical, histological, and GAG changes. Clinical implementation of
      quantitative MRI, T1rho particularly, could aid in distinguishing DDD more
      reliably at an earlier stage in the degenerative process.

PMID- 29381717
TI  - Brief report: Circulating markers of fibrosis are associated with immune
      reconstitution status in HIV-infected men.
AB  - INTRODUCTION: Lymphoid tissue fibrosis may contribute to incomplete immune
      reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4)
      depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4
      concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4
      concentrations in HIV-infected individuals may reflect successful immune evasion
      by HIV. We investigated relationships between circulating HA and CXCL4
      concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS
      Cohort Study participants. METHODS: HIV-infected men on ART for >1 year with
      cryopreserved plasma samples and suppressed post-ART HIV-1 RNA were included. Men
      with post-ART CD4 <200 cells/mm3 were defined as immunologic non-responders (n =
      25). Age-/race-matched men with post-ART CD4 >500 cells/mm3 served as controls (n
      = 49). HA and CXCL4 concentrations were measured via ELISA. RESULTS: Median pre
      ART CD4 was 297 cells/mm3 for non-responders vs 386 cells/mm3 for controls.
      Median post-ART CD4 was 141 cells/mm3 for non-responders and 815 cells/mm3 for
      controls. HIV infection duration was 23 years, with median time on ART 13 years
      for non-responders vs 11 years for controls. Pre-ART HA and CXCL4 concentrations
      did not vary by eventual immune reconstitution status. Post-ART HA concentrations
      tended to be higher (85 vs 36 ng/mL, p = 0.07) and CXCL4 concentrations were
      lower (563 vs 1459 ng/mL, p = 0.01) among non-responders. Among men with paired
      pre-/post-ART samples, non-responders had greater HA increases and CXCL4
      decreases than controls (HA: 50 vs 12 ng/mL, p = 0.04; CXCL4: -1258 vs -405
      ng/mL, p = 0.01). CONCLUSIONS: Higher circulating concentrations of HA and lower
      concentrations of CXCL4 are associated with failure of immune reconstitution on
      ART.

PMID- 29381718
TI  - Effects of long-term cigarette smoke exposure on bone metabolism, structure, and
      quality in a mouse model of emphysema.
AB  - Smoking is a common risk factor for both chronic obstructive pulmonary disease
      (COPD) and osteoporosis. In patients with COPD, severe emphysema is a risk factor
      for vertebral fracture; however, the effects of smoking or emphysema on bone
      health remain largely unknown. We report bone deterioration in a mouse model of
      emphysema induced by nose-only cigarette smoke (CS) exposure. Unexpectedly, short
      term exposure for 4-weeks decreased bone turnover and increased bone volume in
      mice. However, prolonged exposure for 20- and 40-weeks reversed the effects from
      suppression to promotion of bone resorption. This long-term CS exposure increased
      osteoclast number and impaired bone growth, while it increased bone volume.
      Strikingly, long-term CS exposure deteriorated bone quality of the lumbar
      vertebrae as illustrated by disorientation of collagen fibers and the biological
      apatite c-axis. This animal model may provide a better understanding of the
      mechanisms underlying the deterioration of bone quality in pulmonary emphysema
      caused by smoking.

PMID- 29381719
TI  - Positive youth development and observed athlete behavior in recreational sport.
AB  - OBJECTIVES: Competence, confidence, connection, and character are regarded as
      outcomes of positive youth development (PYD) in sport. However, the specific
      athlete behaviors associated with different PYD profiles are not well understood.
      Thus, the purpose of this study was to investigate the relationship between
      athletes' observed behavior during sport competitions and their perceptions of
      PYD outcomes. DESIGN: Cross-sectional study with systematic behavioral
      observation. METHOD: Sixty-seven youth athletes were observed during basketball
      games near the end of their season, and the content of their behavior was
      systematically coded. Athletes also completed measures of the 4 Cs (competence,
      confidence connection, and character). A person-centered analysis approach was
      used to examine the relationship between PYD profiles and observed behavior.
      RESULTS: A cluster analysis identified two homogenous groups of athletes
      characterized by relatively high and low perceptions of confidence, connection,
      and character. A MANCOVA revealed that after controlling for gender and years of
      playing experience, the high Cs group engaged in more frequent sport
      communication with their coaches. CONCLUSIONS: Results re-affirm the critical
      role that coaches play in the developmental experiences of young athletes, and
      highlight the importance of contextual factors of the youth sport environment.

PMID- 29381720
TI  - The impact of Typhoon Haiyan on admissions in two hospitals in Eastern Visayas,
      Philippines.
AB  - OBJECTIVES: We investigated the short-term impact of Typhoon Haiyan, one of the
      strongest typhoons ever to make landfall, on the pattern of admissions in two
      hospitals in Eastern Visayas, the Philippines. METHODS: This study took place at
      Eastern Visayas Regional Medical Center (EVRMC) in Tacloban, and Ormoc District
      Hospital (ODH) in Ormoc. We determined whether there were differences in the
      pattern of admissions between the week before and the three weeks after Haiyan by
      using information on sex, age, diagnosis, ward and outcome at discharge from
      patient records. RESULTS: There was a drop in admissions in both hospitals after
      Haiyan as compared to before. Admissions climbed back to the baseline after ten
      days in EVRMC and after two weeks in ODH. When comparing the period after Haiyan
      to the period before, there was a relative increase in male versus female
      admissions in ODH (OR 2.8, 95%CI 1.7-4.3), but not in EVRMC. Patients aged >=50
      years and 0-14 years had the highest relative increase in admissions. There was a
      relative decrease in admissions for the ICD10 group 'Pregnancy, childbirth and
      the puerperium' (OR 0.4, 95%CI 0.3-0.6), and an increase in 'Certain infectious
      and parasitic diseases' (OR 2.1, 95%CI 1.2-3.5), mainly gastroenteritis, and
      'Diseases of the respiratory system' (OR 1.8, 95%CI 1.0-3.0), mainly pneumonia,
      compared to all other diagnosis groups in ODH. Out of all reasons for admission
      within the study period, 66% belong to these three ICD-10 groups. Data on reasons
      for admission were not available for EVRMC. CONCLUSIONS: The observed reduction
      in patients after the Typhoon calls for ensuring that hospital accessibility
      should be protected and reinforced, especially for pregnant women, by trying to
      remove debris in the direct hospital vicinity. Hospitals in areas prone to
      tropical cyclones should be prepared to treat large numbers of patients with
      gastroenteritis and pneumonia, as part of their disaster plans.

PMID- 29381721
TI  - Transfusion practice in anemic, non-bleeding patients: Cross-sectional survey of
      physicians working in general internal medicine teaching hospitals in
      Switzerland.
AB  - BACKGROUND: Transfusion practice might significantly influence patient morbidity
      and mortality. Between European countries, transfusion practice of red blood
      cells (RBC) greatly differs. Only sparse data are available on transfusion
      practice of general internal medicine physicians in Switzerland. METHODS: In this
      cross-sectional survey, physicians working in general medicine teaching hospitals
      in Switzerland were investigated regarding their self-reported transfusion
      practice in anemic patients without acute bleeding. The definition of anemia,
      transfusion triggers, knowledge on RBC transfusion, and implementation of
      guidelines were assessed. RESULTS: 560 physicians of 71 hospitals (64%) responded
      to the survey. Anemia was defined at very diverging hemoglobin values (by 38% at
      a hemoglobin <130 g/L for men and by 57% at <120 g/L in non-pregnant women). 62%
      and 43% respectively, did not define anemia in men and in women according to the
      World Health Organization. Fifty percent reported not to transfuse RBC according
      to international guidelines. Following factors were indicated to influence the
      decision to transfuse: educational background of the physicians, geographical
      region of employment, severity of anemia, and presence of known coronary artery
      disease. 60% indicated that their knowledge on Transfusion-related Acute Lung
      Injury (TRALI) did not influence transfusion practice. 50% of physicians stated
      that no local transfusion guidelines exist and 84% supported the development of
      national recommendations on transfusion in non-acutely bleeding, anemic patients.
      CONCLUSION: This study highlights the lack of adherence to current transfusion
      guidelines in Switzerland. Identifying and subsequently correcting this deficit
      in knowledge translation may have a significant impact on patient care.

PMID- 29381722
TI  - Mycobacterium leprae genomes from naturally infected nonhuman primates.
AB  - Leprosy is caused by the bacterial pathogens Mycobacterium leprae and
      Mycobacterium lepromatosis. Apart from humans, animals such as nine-banded
      armadillos in the Americas and red squirrels in the British Isles are naturally
      infected with M. leprae. Natural leprosy has also been reported in certain
      nonhuman primates, but it is not known whether these occurrences are due to
      incidental infections by human M. leprae strains or by M. leprae strains specific
      to nonhuman primates. In this study, complete M. leprae genomes from three
      naturally infected nonhuman primates (a chimpanzee from Sierra Leone, a sooty
      mangabey from West Africa, and a cynomolgus macaque from The Philippines) were
      sequenced. Phylogenetic analyses showed that the cynomolgus macaque M. leprae
      strain is most closely related to a human M. leprae strain from New Caledonia,
      whereas the chimpanzee and sooty mangabey M. leprae strains belong to a human M.
      leprae lineage commonly found in West Africa. Additionally, samples from ring
      tailed lemurs from the Beza Mahafaly Special Reserve, Madagascar, and chimpanzees
      from Ngogo, Kibale National Park, Uganda, were screened using quantitative PCR
      assays, to assess the prevalence of M. leprae in wild nonhuman primates. However,
      these samples did not show evidence of M. leprae infection. Overall, this study
      adds genomic data for nonhuman primate M. leprae strains to the existing M.
      leprae literature and finds that this pathogen can be transmitted from humans to
      nonhuman primates as well as between nonhuman primate species. While the
      prevalence of natural leprosy in nonhuman primates is likely low, nevertheless,
      future studies should continue to explore the prevalence of leprosy-causing
      pathogens in the wild.

PMID- 29381723
TI  - Characterization of Penicillium oxalicum SL2 isolated from indoor air and its
      application to the removal of hexavalent chromium.
AB  - Removal of toxic Cr(VI) by microbial reduction is a promising approach to
      reducing its ecotoxicological impact. To develop bioremediation technologies,
      many studies have evaluated the application of microorganisms isolated from
      Cr(VI)-contaminated sites. Nonetheless, little attention has been given to
      microbes from the environments without a history of Cr(VI) contamination. In this
      study, we aimed to characterize the Cr(VI) tolerance and removal abilities of a
      filamentous fungus strain, SL2, isolated from indoor air. Based on phenotypic
      characterization and rDNA sequence analysis, SL2 was identified as Penicillium
      oxalicum, a species that has not been extensively studied regarding Cr(VI)
      tolerance and reduction abilities. SL2 showed high tolerance to Cr(VI) on solid
      and in liquid media, facilitating its application to Cr(VI)-contaminated
      environments. Growth curves of SL2 in the presence of 0, 100, 400, or 1000 mg/L
      Cr(VI) were well simulated by the modified Gompertz model. The relative maximal
      colony diameter and maximal growth rate decreased as Cr(VI) concentration
      increased, while the lag time increased. SL2 manifested remarkable efficacy of
      removing Cr(VI). Mass balance analysis indicated that SL2 removed Cr(VI) by
      reduction, and incorporated 0.79 mg of Cr per gram of dry biomass. In
      electroplating wastewater, the initial rate of Cr(VI) removal was affected by the
      initial contaminant concentration. In conclusion, P. oxalicum SL2 represents a
      promising new candidate for Cr(VI) removal. Our results significantly expand the
      knowledge on potential application of this microorganism.

PMID- 29381724
TI  - Non-linear models for the detection of impaired cerebral blood flow
      autoregulation.
AB  - The ability to discriminate between normal and impaired dynamic cerebral
      autoregulation (CA), based on measurements of spontaneous fluctuations in
      arterial blood pressure (BP) and cerebral blood flow (CBF), has considerable
      clinical relevance. We studied 45 normal subjects at rest and under hypercapnia
      induced by breathing a mixture of carbon dioxide and air. Non-linear models with
      BP as input and CBF velocity (CBFV) as output, were implemented with support
      vector machines (SVM) using separate recordings for learning and validation.
      Dynamic SVM implementations used either moving average or autoregressive
      structures. The efficiency of dynamic CA was estimated from the model's derived
      CBFV response to a step change in BP as an autoregulation index for both linear
      and non-linear models. Non-linear models with recurrences (autoregressive) showed
      the best results, with CA indexes of 5.9 +/- 1.5 in normocapnia, and 2.5 +/- 1.2
      for hypercapnia with an area under the receiver-operator curve of 0.955. The high
      performance achieved by non-linear SVM models to detect deterioration of dynamic
      CA should encourage further assessment of its applicability to clinical
      conditions where CA might be impaired.

PMID- 29381725
TI  - Long-term effect of motor cortex stimulation in patients suffering from chronic
      neuropathic pain: An observational study.
AB  - BACKGROUND: Motor cortex stimulation (MCS) was introduced as a last-resort
      treatment for chronic neuropathic pain. Over the years, MCS has been used for the
      treatment of various pain syndromes but long-term follow-up is unknown. METHODS:
      This paper reports the results of MCS from 2005 until 2012 with a 3-year follow
      up. Patients who suffered from chronic neuropathic pain treated with MCS were
      studied. The analgesic effect was determined as successful by decrease in pain
      intensity on the visual analog scale (VAS) of at least 40%. The modifications in
      drug regimens were monitored with use of the medication quantification scale
      (MQS). Stimulation parameters and complications were also noted. Interference of
      pain with quality of life (QoL), the Quality of Life Index (QLI), was determined
      with use of a specific subset of questions from the MPQ-DLV score. RESULTS:
      Eighteen patients were included. Mean pre-operative VAS changed from 89.4 +/-
      11.2 to 53.1 +/- 25.0 after three years of follow-up (P < 0.0001). A successful
      outcome was achieved in seven responders (38.9%). All patients in the responder
      group suffered from pain caused by a central lesion. With regard to all the
      patients with central pain lesions (n = 10) and peripheral lesions (n = 8), a
      significant difference in response to MCS was noticed (P = 0.002). MQS scores and
      QLI-scores diminished during the follow-up period (P = 0.210 and P = 0.007,
      respectively). CONCLUSION: MCS seems a promising therapeutic option for patients
      with refractory pain syndromes of central origin.

PMID- 29381726
TI  - A single-center randomized controlled trial observing the safety and efficacy of
      modified step-up graded Valsalva manoeuver in patients with vasovagal syncope.
AB  - Non-pharmacological therapies, especially the physical maneuvers, are viewed as
      important and promising strategies for reducing syncope recurrences in vasovagal
      syncope (VVS) patients. We observed the efficacy of a modified Valsalva maneuver
      (MVM) in VVS patients. 72 VVS patients with syncope history and positive head-up
      tilt table testing (HUTT) results were randomly divided into conventional
      treatment group (NVM group, n = 36) and conventional treatment plus standard MVM
      for 30 days group (MVM group, n = 36). Incidence of recurrent syncope after 12
      months (6.5% vs. 41.2%, P<0.01) and rate of positive HUTT after 30 days (9.7%
      vs.79.4%, P<0.01) were significantly lower in MVM group than in NVM group. HRV
      results showed that low frequency (LF), LF/ high frequency (HF), standard
      deviation of NN intervals (SDNN) and standard deviation of all 5-min average NN
      intervals (SDANN) values were significantly lower in the NVM and MVM groups than
      in the control group at baseline. After 30 days treatment, LF, LF/HF, SDNN, SDANN
      values were significantly higher compared to baseline in MVM group. Results of
      Cox proportional hazard model showed that higher SDNN and SDANN values at 30 days
      after intervention were protective factors, while positive HUTT at 30 days after
      intervention was risk factor for recurrent syncope. Our results indicate that 30
      days MVM intervention could effectively reduce the incidence of recurrent syncope
      up to 12 months in VVS patients, possibly through improving sympathetic function
      of VVS patients.

PMID- 29381727
TI  - Effects of blue light on flavonoid accumulation linked to the expression of
      miR393, miR394 and miR395 in longan embryogenic calli.
AB  - While flavonoid metabolism's regulation under light conditions by structural
      genes and transcription factors is understood, the roles of microRNAs (miRNAs) in
      this pathway have been rarely reported. In this paper, the accurate control of
      light was firstly enabled through the specially designed plant growth chamber
      which ensures consistency and accuracy of the cultivation of longan ECs and the
      repeatability of the experiments. Then, longan ECs were cultured in this chamber
      for 25 days. The change of growth rate of longan ECs was compared under different
      light qualities (dark, blue, green, white, green), intensities (16, 32, 64, 128,
      256 MUmol .m-2 .s-1), and durations (8 h, 12 h, 16 h, 20h, 24h). Results
      indicated that longan ECs had a high growth rate in the condition of blue or
      green light, at intensity ranged from 16 MUmol.m-2.s-1 to 64 MUmol.m-2.s-1, and
      duration from 8 h to 16 h. In addition, the contents of total flavonoids, rutin,
      and epicatechin were determined. Results indicated that flavonoid contents of
      longan ECs reached the highest value under blue light, at 32 MUmol.m-2.s-1 and
      12h/d. Blue light promoted the accumulation of epicatechin, but inhibited the
      synthesis of rutin. Finally, the expressions of flavonoid pathway genes, miRNAs
      and target genes were analyzed by qPCR. These results indicated that miR393 and
      its target gene DlTIR1-3, miR394 and its target gene DlAlMT12, and miR395 and its
      target gene DlAPS1 had a negative regulating relationship under blue light in
      longan ECs. Furthermore, miR393, miR394, and miR395 acted on target genes, which
      negatively regulated flavonoid key genes DlFLS and positively regulated key genes
      DlCHS, DlCHI, DlF3'H, DlDFR, DlLAR, and finally affected the accumulation of
      flavonoids. The treatment of longan ECs under the blue light at the intensity of
      32 MUmol.m-2.s-1 for 12 h/d inhibited the expression of miR393, miR394 and
      miR395, which promoted the expression of target genes and the accumulation of
      flavonoids and epicatechin, but inhibited the synthesis of rutin.

PMID- 29381728
TI  - M60-like metalloprotease domain of the Escherichia coli YghJ protein forms
      amyloid fibrils.
AB  - Amyloids are protein fibrils with a characteristic spatial structure. Amyloids
      were long perceived as the pathogens involved in a set of lethal diseases in
      humans and animals. In recent decades, it has become clear that amyloids
      represent a quaternary protein structure that is not only pathological but also
      functionally important and is widely used by different organisms, ranging from
      archaea to animals, to implement diverse biological functions. The greatest
      biological variety of amyloids is found in prokaryotes, where they control the
      formation of biofilms and cell wall sheaths, facilitate the overcoming of surface
      tension, and regulate the metabolism of toxins. Several amyloid proteins were
      identified in the important model, biotechnological and pathogenic bacterium
      Escherichia coli. In previous studies, using a method for the proteomic screening
      and identification of amyloids, we identified 61 potentially amyloidogenic
      proteins in the proteome of E. coli. Among these proteins, YghJ was the most
      enriched with bioinformatically predicted amyloidogenic regions. YghJ is a
      lipoprotein with a zinc metalloprotease M60-like domain that is involved in mucin
      degradation in the intestine as well as in proinflammatory responses. In this
      study, we analyzed the amyloid properties of the YghJ M60-like domain and
      demonstrated that it forms amyloid-like fibrils in vitro and in vivo.

PMID- 29381729
TI  - bmo-miR-275 down-regulates expression of Bombyx mori sericin gene 2 in vitro.
AB  - We hypothesized that bmo-miR-275 has a potential regulatory function regarding
      the expression of sericin gene 2 (BmSer-2). First, we examined the expression of
      bmo-miR-275 and its target gene BmSer-2 in seven different tissues from 5th
      instar day-3 silkworm larvae. The results showed that they were both specifically
      expressed in the middle silk gland, implying that spatio-temporal conditions are
      required for bmo-miR-275 to regulate the expression of BmSer-2. To test this
      hypothesis, we constructed a pri-bmo-miR-275 expressing plasmid pcDNA3.0 [ie1
      egfp-pri-bmo-miR-275-SV40] and BmSer-2-3'UTR recombinant reporter plasmids pGL3.0
      [A3-luc-Ser-2-3' UTR-SV40]. Finally, BmN cells were harvested and luciferase
      activity was detected. Results showed that luciferase activity was reduced
      significantly (P<0.05) in BmN cells co-transfected with pcDNA3.0 [ie1-egfp-pri
      bmo-miR-275-SV40] and pGL3.0 [A3-luc-Ser-2-3'UTR-SV40], suggesting that bmo-miR
      275 can down-regulate the expression of BmSer-2 in vitro. Our results improve the
      understanding of the regulatory function of Bombyx mori miRNA on the expression
      of genes regulating silk formation.

PMID- 29381730
TI  - Assessing the integrity of the cognitive processes involved in belief reasoning
      by means of two nonverbal tasks: Rationale, normative data collection and
      illustration with brain-damaged patients.
AB  - Every day, we engage in social interactions with other people which require
      understanding their as well as our own mental states. Such capacity is commonly
      referred to as Theory of Mind (ToM). Disturbances of ToM are often reported in
      diverse pathologies which affect brain functioning and lead to problems in social
      interactions. Identifying ToM deficits is thus crucial to guide the clinicians in
      the establishment of adequate rehabilitation strategies for patients. Previous
      studies have demonstrated that ToM is not a unitary function yet currently there
      are very few standardized tests which allow identifying the type of cognitive
      processes affected when a patient exhibits a ToM deficit. In the current study,
      we present two belief reasoning tasks which have been used in previous research
      to disentangle two types of processes involved in belief reasoning: self
      perspective inhibition and the spontaneous inference of another person's belief.
      A three-step procedure was developed to provide clinicians with the tools to
      interpret the patients' performances on the tasks. First, these tasks were
      standardized and normative data was collected on a sample of 124 healthy
      participants aged between 18 and 74. Data collected showed a decrease in
      performance as a function of age only in the task that loaded most in spontaneous
      other-perspective demands. There was however no effect of gender or educational
      level. Cut-off scores to identify deficits were then calculated for the different
      age groups separately. Secondly, the three-step procedure was applied to 21 brain
      damaged patients and showed a large diversity of profiles, including selective
      deficits of the two targeted ToM processes. The diversity of profiles shows the
      importance to take into account the multiple facets of ToM during the diagnosis
      and rehabilitation of patients with suspected ToM deficits.

PMID- 29381732
TI  - Polyphenol estimated intake and dietary sources among older adults from Mallorca
      Island.
AB  - The aim was the assessment of the polyphenol estimated intake and dietary sources
      among older adults from Mallorca Island. The study was carried out (2013-2014) in
      211 participants dwelling women (n = 112) and men (n = 99). Polyphenol intake was
      calculated from two non-consecutive 24-h recall diets using the Polyphenol
      Explorer. The mean daily intake of polyphenol was 332.7 mg/d (SD: 237.9; median:
      299 mg/d). Highest polyphenol intake was observed among females, 64-67 y.o.
      people, higher income and educational level, alcohol consumers, and physically
      active people. Most polyphenols consumed were flavonoids, and among them the
      major subclass was flavanols. Alcoholic beverages were the major contributors to
      the total polyphenol intake (118.3 mg/d, SD: 127.5), and red wine contributed
      17.7% of total polyphenols consumed. Polyphenol intake was highest among alcohol
      drinkers, high educational level, high income, and physical active people.
      Flavonoids were the highest ingested polyphenols. Alcoholic beverages were the
      major contributors to the total polyphenol intake, mainly red wine.

PMID- 29381731
TI  - The prognostic value of HER2 in ovarian cancer: A meta-analysis of observational
      studies.
AB  - BACKGROUND: The prognostic role of human epidermal growth factor receptor 2
      (HER2) in ovarian cancer has been investigated in previous studies, but the
      results remain controversial. Here we present a meta-analysis to systematically
      review the association between HER2 expression and ovarian cancer prognosis.
      METHOD: Observational studies published until July 2017 were searched in Pubmed,
      Embase, and Cochrane library databases. Hazard ratios (HRs) for survival with 95%
      confidence intervals (CIs), subgroup analyses, publication bias and sensitivity
      analyses were implemented under a standard manner. Estimates of overall survival
      (OS), progress-free survival (PFS) and disease-free survival (DFS) were weighted
      and pooled using Der Simonian-Laird random-effect model. RESULT: Thirty-four
      studies that include 5180 ovarian cancer patients were collected for analysis.
      Expression of HER2 was negatively correlated with clinical prognosis of overall
      survival (HR = 1.57, 95% CI: 1.31 to 1.89, P < 0.001) and disease-free survival /
      progress-free survival (HR = 1.26, 95% CI = 1.06 to 1.49) in ovarian cancers. The
      association between HER2 expression and poor ovarian cancer prognosis in overall
      survival was also statistically significant in subgroups of unclassified ovarian
      cancer, Caucasian population and Asian population, while irrespective of
      detection method. CONCLUSION: HER2 expression was related with poor prognosis in
      ovarian cancer patients and can be used as a predicting cancer prognostic
      biomarker in ovarian cancer patients.

PMID- 29381733
TI  - Prognostic effects of delirium motor subtypes in hospitalized older adults: A
      prospective cohort study.
AB  - OBJECTIVES: To investigate the association between delirium motor subtypes and
      hospital mortality and 12-month mortality in hospitalized older adults. DESIGN:
      Prospective cohort study conducted from 2009 to 2015. SETTING: Geriatric ward of
      a university hospital in Sao Paulo, Brazil. PARTICIPANTS: We included 1,409
      consecutive admissions of acutely ill patients aged 60 years and over. We
      excluded admissions for end-of-life care, with missing data on the main
      variables, length of stay shorter than 48 hours, or when consent to participate
      was not given. MAIN OUTCOMES AND MEASURES: Delirium was detected using the
      Confusion Assessment Method and categorized in hypoactive, hyperactive, or mixed
      delirium. Primary outcomes were time to death in the hospital, and time to death
      in 12 months (for the discharged sample). Comprehensive geriatric assessment was
      performed at admission and included socio-demographic, clinical, functional,
      cognitive, and laboratory variables. Further clinical data were documented upon
      death or discharge. Multivariate analyses used Cox proportional hazards models
      adjusted for possible confounders. RESULTS: We included 1,409 admissions, with a
      mean age of 80 years. The proportion of in-hospital deaths was 19%, with a
      cumulative mortality of 38% in 12 months. Delirium occurred in 47% of the
      admissions. Hypoactive delirium was the predominant motor subtype (53%), followed
      by mixed delirium (30%) and hyperactive delirium (17%). Hospital mortality rates
      were respectively 33%, 34% and 15%. We verified that hypoactive and mixed
      delirium were independently associated with hospital mortality, with respective
      hazard ratios of 2.43 (95%CI = 1.64-3.59) and 2.31 (95%CI = 1.53-3.50). Delirium
      motor subtypes were not independently predictive of 12-month mortality.
      CONCLUSIONS: One in three acutely ill hospitalized older adults who suffered
      hypoactive or mixed delirium died in the hospital. Clinicians should be aware
      that hypoactive symptoms of delirium, whether shown exclusively or in alternation
      with hyperactive symptoms, are indicative of a worse prognosis in this
      population.

PMID- 29381734
TI  - Socioeconomic differences in smoking in Jordan, Lebanon, Syria, and Palestine: A
      cross-sectional analysis of national surveys.
AB  - INTRODUCTION: The association between education and wealth, as fundamental
      determinants of health, and smoking is well-established. Yet, social inequalities
      have received little attention in the expanding field of tobacco research in the
      Arab region. In this study, we examine inequalities in cigarette smoking by
      education and wealth in four Arab countries. METHODS: Utilizing the most recently
      available population-level data sets (Syria 2009 PAPFAM, Jordan 2012 DHS,
      Palestine 2010 Family Health Survey, and Lebanon 2004 PAPFAM), we tested the
      association between cigarette smoking and education and wealth-controlling for
      age, marital status, and region of residence-for each country, and among men and
      women depending on data availability. RESULTS: Cigarette smoking prevalence among
      Arab men is high- 51.3% in Syria, 39.7% in Palestine, and 42.1% in Lebanon; among
      women, prevalence is 8.4% in Syria, 10.9% in Jordan, and 24.3% Lebanon. Cigarette
      smoking shows the expected patterns inequalities by education among men in Syria,
      Palestine, and Lebanon, and among women in Jordan and Lebanon. On the other hand,
      wealth does not show a clear pattern in its association with cigarette smoking
      and, in some cases (men in Palestine and women in Syria) the behavioral risk is
      higher among the wealthiest. CONCLUSIONS: Available data from 2004-2012 show that
      cigarette smoking among men and women in the four Arab countries is predominant
      among those with limited access to education as a fundamental cause. The weak or
      absent negative association between wealth and cigarette smoking suggests that
      access to material resources does not precipitate a reduction in the consumption
      of tobacco.

PMID- 29381735
TI  - Correction: Maternal gestational weight gain and objectively measured physical
      activity among offspring.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180249.].

PMID- 29381736
TI  - Virologic outcome among patients receiving antiretroviral therapy at five
      hospitals in Haiti.
AB  - INTRODUCTION: Viral load (VL) assessment is the preferred method for diagnosing
      and confirming virologic failure for patients on antiretroviral therapy (ART). We
      conducted a retrospective cross-sectional study to evaluate the virologic
      suppression rate among patients on ART for >=6 months in five hospitals around
      Port-au-Prince, Haiti. METHODS: Plasma VL was measured and patients with VL
      <1,000 copies/mL were defined as virologically suppressed. A second VL test was
      performed within at least six months of the first test. Factors associated with
      virologic suppression were analyzed using logistic regression models accounting
      for site-level clustering using complex survey procedures. RESULTS: Data were
      analyzed for 2,313 patients on ART for six months or longer between July 2013 and
      February 2015. Among them, 1,563 (67.6%) achieved virologic suppression at the
      first VL test. A second VL test was performed within at least six months for 718
      (31.0%) of the patients. Of the 459 patients with an initial HIV-1 RNA <1,000
      copies/mL who had a second VL performed, 394 (85.8%) maintained virologic
      suppression. Virologic suppression was negatively associated with male gender
      (adjusted odds ratio [aOR]: 0.80, 95% CI: 0.74-0.0.86), 23 to 35 months on ART
      (aOR:0.72[0.54-0.96]), baseline CD4 counts of 201-500 cells/mm3 and 200 cells/mm3
      or lower (aORs: 0.77 [0.62-0.95] and 0.80 [0.66-0.98], respectively), poor
      adherence (aOR: 0.69 [0.59-0.81]), and TB co-infection (aOR: 0.73 [0.55-0.97]).
      CONCLUSIONS: This study showed that over two-thirds of the patients in this
      evaluation achieved virologic suppression after >= six months on ART and the
      majority of them remained suppressed. These results reinforce the importance of
      expanding access to HIV-1 viral load testing in Haiti for monitoring ART
      outcomes.

PMID- 29381738
TI  - Correction: Intestinal Ralstonia pickettii augments glucose intolerance in
      obesity.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0181693.].

PMID- 29381737
TI  - Identification and functional analysis of two alternatively spliced transcripts
      of ABSCISIC ACID INSENSITIVE3 (ABI3) in linseed flax (Linum usitatissimum L.).
AB  - Alternative splicing is a popular phenomenon in different types of plants. It can
      produce alternative spliced transcripts that encode proteins with altered
      functions. Previous studies have shown that one transcription factor, ABSCISIC
      ACID INSENSITIVE3 (ABI3), which encodes an important component in abscisic acid
      (ABA) signaling, is subjected to alternative splicing in both mono- and
      dicotyledons. In the current study, we identified two homologs of ABI3 in the
      genome of linseed flax. We screened two alternatively spliced flax LuABI3
      transcripts, LuABI3-2 and LuABI3-3, and one normal flax LuABI3 transcript, LuABI3
      1. Sequence analysis revealed that one of the alternatively spliced transcripts,
      LuABI3-3, retained a 6 bp intron. RNA accumulation analysis showed that all three
      transcripts were expressed during seed development, while subcellular
      localization and transgene experiments showed that LuABI3-3 had no biological
      function. The two normal transcripts, LuABI3-1 and LuABI3-2, are the important
      functional isoforms in flax and play significant roles in the ABA regulatory
      pathway during seed development, germination, and maturation.

PMID- 29381739
TI  - Impaired memory is more closely associated with brain beta-amyloid than
      leukoaraiosis in hypertensive patients with cognitive symptoms.
AB  - BACKGROUND: Hypertension is the strongest modifiable risk factor for subcortical
      ischemic changes and is also a risk factor for Alzheimer's dementia. We used
      neuroimaging to investigate the pathological basis of early cognitive symptoms in
      patients with hypertension. METHODS: In this cross-sectional cohort study 67
      patients age >60 years with hypertension and Clinical Dementia Rating scale score
      of 0.5 without dementia, and without history of symptomatic stroke, underwent MRI
      for measurement of subcortical vascular changes and positron emission tomography
      (PET) scan with Pittsburgh Compound B (PiB-PET) to detect beta-amyloid
      deposition. These imaging measures were related to neuropsychological tests of
      memory, executive function and processing speed. RESULTS: Mean age was 75.0
      (standard deviation, SD, 7.3). Mean neuropsychological Z scores were: episodic
      memory -0.63 (SD 1.23), executive function -0.40 (SD 1.10), processing speed 
      0.24 (SD 0.88); 22 of the 67 subjects met criteria for mild cognitive impairment
      (MCI) and the remaining 45 subjects had subjective cognitive concerns only. In
      multivariable models adjusting for age and years of education, each 0.1 unit
      increase in mean cortical PiB-PET binding was associated with 0.14 lower mean Z
      score for episodic memory (95% CI -0.28 to -0.01). This means that for every 0.1
      unit increase in mean cortical PiB-PET, episodic memory was 0.14 standard
      deviations lower. White matter hyperintensity volume, silent brain infarcts and
      microbleeds were not associated with neuropsychological test scores. CONCLUSIONS:
      Episodic memory was prominently affected in hypertensive participants with MCI or
      subjective cognitive concerns, and was associated with PiB-PET binding. This
      suggests a prominent role for Alzheimer pathology in cognitive impairment even in
      hypertensive participants at elevated risk for vascular cognitive impairment.

PMID- 29381740
TI  - Variation in grain Zn concentration, and the grain ionome, in field-grown Indian
      wheat.
AB  - Wheat is an important dietary source of zinc (Zn) and other mineral elements in
      many countries. Dietary Zn deficiency is widespread, especially in developing
      countries, and breeding (genetic biofortification) through the HarvestPlus
      programme has recently started to deliver new wheat varieties to help alleviate
      this problem in South Asia. To better understand the potential of wheat to
      alleviate dietary Zn deficiency, this study aimed to characterise the baseline
      effects of genotype (G), site (E), and genotype by site interactions (GxE) on
      grain Zn concentration under a wide range of soil conditions in India. Field
      experiments were conducted on a diverse panel of 36 Indian-adapted wheat
      genotypes, grown on a range of soil types (pH range 4.5-9.5), in 2013-14 (five
      sites) and 2014-15 (six sites). Grain samples were analysed using inductively
      coupled plasma-mass spectrometry (ICP-MS). The mean grain Zn concentration of the
      genotypes ranged from 24.9-34.8 mg kg-1, averaged across site and year. Genotype
      and site effects were associated with 10% and 6% of the overall variation in
      grain Zn concentration, respectively. Whilst G x E interaction effects were
      evident across the panel, some genotypes had consistent rankings between sites
      and years. Grain Zn concentration correlated positively with grain concentrations
      of iron (Fe), sulphur (S), and eight other elements, but did not correlate
      negatively with grain yield, i.e. no yield dilution was observed. Despite a
      relatively small contribution of genotype to the overall variation in grain Zn
      concentration, due to experiments being conducted across many contrasting sites
      and two years, our data are consistent with reports that biofortifying wheat
      through breeding is likely to be effective at scale given that some genotypes
      performed consistently across diverse soil types. Notably, all soils in this
      study were probably Zn deficient and interactions between wheat genotypes and
      soil Zn availability/management (e.g. the use of Zn-containing fertilisers) need
      to be better-understood to improve Zn supply in food systems.

PMID- 29381741
TI  - Overexpression of MYB115, AAD2, or AAD3 in Arabidopsis thaliana seeds yields
      contrasting omega-7 contents.
AB  - Omega-7 monoenoic fatty acids (omega-7 FAs) are increasingly exploited both for
      their positive effects on health and for their industrial potential. Some plant
      species produce fruits or seeds with high amounts of omega-7 FAs. However, the
      low yields and poor agronomic properties of these plants preclude their
      commercial use. As an alternative, the metabolic engineering of oilseed crops for
      sustainable omega-7 FA production has been proposed. Two palmitoyl-ACP
      desaturases (PADs) catalyzing omega-7 FA biosynthesis were recently identified
      and characterized in Arabidopsis thaliana, together with MYB115 and MYB118, two
      transcription factors that positively control the expression of the corresponding
      PAD genes. In the present research, we examine the biotechnological potential of
      these new actors of omega-7 metabolism for the metabolic engineering of plant
      based production of omega-7 FAs. We placed the PAD and MYB115 coding sequences
      under the control of a promoter strongly induced in seeds and evaluated these
      different constructs in A. thaliana. Seeds were obtained that exhibit omega-7 FA
      contents ranging from 10 to >50% of the total FAs, and these major compositional
      changes have no detrimental effect on seed germination.

PMID- 29381742
TI  - Correction: Aerobic Exercise Training in Post-Polio Syndrome: Process Evaluation
      of a Randomized Controlled Trial.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0159280.].

PMID- 29381743
TI  - Correction: Adolescent Depression and Negative Life Events, the Mediating Role of
      Cognitive Emotion Regulation.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0161062.].

PMID- 29381744
TI  - Irisin, physical activity and fitness status in healthy humans: No association
      under resting conditions in a cross-sectional study.
AB  - Regular physical activity and physical fitness are closely related to a positive
      health status in humans. In this context, the muscle becomes more important due
      to its function as an endocrine organ. Muscle tissue secretes "myokines" in
      response to physical activity and it is speculated that these myokines are
      involved in physical activity induced positive health effects. Recently, the
      newly discovered myokine Irisin thought to be secreted by the muscle in response
      to physical activity and might be related to the health inducing effect by
      inducing browning of white adipose tissue. Speculating that myokines at least
      partly mediate exercise related health effects one would assume that regular
      physical activity and physical fitness are associated with resting Irisin
      concentrations in healthy humans. To investigate the association between resting
      Irisin concentration and either short-term physical activity, habitual physical
      activity, or physical fitness, data of 300 healthy participants from the cross
      sectional KarMeN-study were analyzed. By applying different activity measurements
      we determined short-term and habitual physical activity, as well as physical
      fitness. Fasting serum samples were collected to determine resting Irisin
      concentrations by Enzyme-linked Immunosorbent Assay. Multivariate linear
      regression analysis served to investigate associations of the individual physical
      activity parameters with Irisin concentrations. Therefore, lean body mass and
      total fat mass (both determined by dual-energy X-ray absorptiometry) as well as
      age and parameters of glucose metabolism were included as confounders in
      multivariate linear regression analysis. Results showed that Irisin serum
      concentrations were not related to measures of physical activity and physical
      fitness in healthy humans under resting conditions, irrespective of the applied
      methods. Therefore we assume that if physical activity related effects are partly
      induced by myokines, permanently increased Irisin serum concentration may not be
      necessary to induce health-related exercise effects.

PMID- 29381745
TI  - Using community-based reporting of vital events to monitor child mortality:
      Lessons from rural Ghana.
AB  - BACKGROUND: Reducing neonatal and child mortality is a key component of the
      health-related sustainable development goal (SDG), but most low and middle income
      countries lack data to monitor child mortality on an annual basis. We tested a
      mortality monitoring system based on the continuous recording of pregnancies,
      births and deaths by trained community-based volunteers (CBV). METHODS AND
      FINDINGS: This project was implemented in 96 clusters located in three districts
      of the Northern Region of Ghana. Community-based volunteers (CBVs) were selected
      from these clusters and were trained in recording all pregnancies, births, and
      deaths among children under 5 in their catchment areas. Data collection lasted
      from January 2012 through September 2013. All CBVs transmitted tallies of
      recorded births and deaths to the Ghana Birth and deaths registry each month,
      except in one of the study districts (approximately 80% reporting). Some events
      were reported only several months after they had occurred. We assessed the
      completeness and accuracy of CBV data by comparing them to retrospective full
      pregnancy histories (FPH) collected during a census of the same clusters
      conducted in October-December 2013. We conducted all analyses separately by
      district, as well as for the combined sample of all districts. During the 21
      month implementation period, the CBVs reported a total of 2,819 births and 137
      under-five deaths. Among the latter, there were 84 infant deaths (55 neonatal
      deaths and 29 post-neonatal deaths). Comparison of the CBV data with FPH data
      suggested that CBVs significantly under-estimated child mortality: the estimated
      under-5 mortality rate according to CBV data was only 2/3 of the rate estimated
      from FPH data (95% Confidence Interval for the ratio of the two rates = 51.7 to
      81.4). The discrepancies between the CBV and FPH estimates of infant and neonatal
      mortality were more limited, but varied significantly across districts.
      CONCLUSIONS: In northern Ghana, a community-based data collection systems relying
      on volunteers did not yield accurate estimates of child mortality rates.
      Additional implementation research is needed to improve the timeliness,
      completeness and accuracy of such systems. Enhancing pregnancy monitoring, in
      particular, may be an essential step to improve the measurement of neonatal
      mortality.

PMID- 29381746
TI  - Time course of immature platelet count and its relation to thrombocytopenia and
      mortality in patients with sepsis.
AB  - INTRODUCTION: The pathogenesis of thrombocytopenia in patients with sepsis is not
      fully understood. The aims of this study were to investigate changes in
      thrombopoietic activity over time by using absolute immature platelet counts
      (AIPC) and to examine the impact of platelet production on thrombocytopenia and
      mortality in patients with sepsis. METHODS: This retrospective observational
      study included adult patients with sepsis admitted to the intensive care unit at
      a university hospital. Two hundred five consecutive sepsis patients were
      stratified into four groups according to nadir platelet count: severe (nadir
      <=40*103/MUL), moderate (41-80*103/MUL), or mild thrombocytopenia (81
      120*103/MUL), or normal-increased platelet count (>120*103/MUL). The development
      of thrombocytopenia was assessed during the first week; mortality was assessed at
      day 28. RESULT: Of the 205 patients included, 61 (29.8%) developed severe
      thrombocytopenia. On admission, AIPC did not differ among the four groups. In
      patients with severe thrombocytopenia, AIPC decreased significantly from days 2
      to 7, but remained within or above the normal range in the other three groups
      (overall group comparison, P<0.0001). Multivariate analysis including coagulation
      biomarkers revealed that AIPC was independently associated with the development
      of severe thrombocytopenia (day 3 AIPC, odds ratio 0.49 [95% confidence interval
      (CI) 0.35-0.66], P<0.0001; day 5 AIPC, 0.59 [95% CI 0.45-0.75], P<0.0001). AIPC
      was a significant predictor of 28-day mortality in Cox hazard models adjusted for
      Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure
      Assessment scores (day 3 AIPC, hazard ratio 0.70 [95% CI 0.52-0.89], P = 0.0029;
      day 5 AIPC, 0.68 [95% CI 0.49-0.87], P = 0.0012). CONCLUSIONS: Thrombopoietic
      activity was generally maintained in the acute phase of sepsis. However, a
      decrease in AIPC after admission was independently associated with the
      development of severe thrombocytopenia and mortality, suggesting the importance
      of suppressed thrombopoiesis in the pathophysiology of sepsis-induced
      thrombocytopenia.

PMID- 29381747
TI  - Extrinsic grouping factors in motion-induced blindness.
AB  - We investigated how various grouping factors altered subjective disappearances of
      the individual targets in the motion-induced blindness display. The latter relies
      on a moving mask to render highly salient static targets temporarily subjectively
      invisible. Specifically, we employed two extrinsic grouping factors, the
      connectedness and the common region, and examined whether their presence would
      make targets more resilient against the suppression. In addition, we investigated
      whether the presence of an illusory Kanizsa triangle would affect the suppression
      of the inducing Pac-Man elements. We quantified the perceptual dynamics using the
      proportion of the disappearance time (this indicates whether targets became more
      resilient against the suppression), and the proportion of simultaneous
      disappearance and reappearance events (characterizes the tendency for the targets
      to disappear or reappear as a group). We report that a single mask that
      encompassed all targets (a common region grouping) significantly increased the
      proportion of simultaneous disappearance and reappearance events, but had no
      effect on the proportion of the disappearance time. In contrast, a line that
      connected two targets significantly decreased the total invisibility time, but
      had no impact on the simultaneity of the disappearance and reappearance events.
      We found no statistically significant effect of the presence of the illusory
      Kanizsa triangle on either measure. Finally, we found no interaction either
      between the common region and the connectedness or between the common region and
      the presence of the illusory Kanizsa triangle. Our results indicate that
      extrinsic grouping factors might influence the perception differently than the
      intrinsic ones and highlight the importance of using several measures to
      characterize the perceptual dynamics, as various grouping factors might affect it
      differentially.

PMID- 29381749
TI  - Correction: T cell activation and differentiation is modulated by a CD6 domain 1
      antibody Itolizumab.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180088.].

PMID- 29381748
TI  - Common neural structures activated by epidural and transcutaneous lumbar spinal
      cord stimulation: Elicitation of posterior root-muscle reflexes.
AB  - Epidural electrical stimulation of the lumbar spinal cord is currently regaining
      momentum as a neuromodulation intervention in spinal cord injury (SCI) to modify
      dysregulated sensorimotor functions and augment residual motor capacity. There is
      ample evidence that it engages spinal circuits through the electrical stimulation
      of large-to-medium diameter afferent fibers within lumbar and upper sacral
      posterior roots. Recent pilot studies suggested that the surface electrode-based
      method of transcutaneous spinal cord stimulation (SCS) may produce similar
      neuromodulatory effects as caused by epidural SCS. Neurophysiological and
      computer modeling studies proposed that this noninvasive technique stimulates
      posterior-root fibers as well, likely activating similar input structures to the
      spinal cord as epidural stimulation. Here, we add a yet missing piece of evidence
      substantiating this assumption. We conducted in-depth analyses and direct
      comparisons of the electromyographic (EMG) characteristics of short-latency
      responses in multiple leg muscles to both stimulation techniques derived from ten
      individuals with SCI each. Post-activation depression of responses evoked by
      paired pulses applied either epidurally or transcutaneously confirmed the reflex
      nature of the responses. The muscle responses to both techniques had the same
      latencies, EMG peak-to-peak amplitudes, and waveforms, except for smaller
      responses with shorter onset latencies in the triceps surae muscle group and
      shorter offsets of the responses in the biceps femoris muscle during epidural
      stimulation. Responses obtained in three subjects tested with both methods at
      different time points had near-identical waveforms per muscle group as well as
      same onset latencies. The present results strongly corroborate the activation of
      common neural input structures to the lumbar spinal cord-predominantly primary
      afferent fibers within multiple posterior roots-by both techniques and add to
      unraveling the basic mechanisms underlying electrical SCS.

PMID- 29381750
TI  - The advertisement calls of Brazilian anurans: Historical review, current
      knowledge and future directions.
AB  - Advertisement calls are often used as essential basic information in studies of
      animal behaviour, ecology, evolution, conservation, taxonomy or biodiversity
      inventories. Yet the description of this type of acoustic signals is far to be
      completed, especially in tropical regions, and is frequently non-standardized or
      limited in information, restricting the application of bioacoustics in science.
      Here we conducted a scientometric review of the described adverstisement calls of
      anuran species of Brazil, the world richest territory in anurans, to evaluate the
      amount, standard and trends of the knowledge on this key life-history trait and
      to identify gaps and directions for future research strategies. Based on our
      review, 607 studies have been published between 1960 to 2016 describing the calls
      of 719 Brazilian anuran species (68.8% of all species), a publication rate of
      10.6 descriptions per year. From each of these studies, thirty-one variables were
      recorded and examined with descriptive and inferential statistics. In spite of an
      exponential rise over the last six decades in the number of studies, described
      calls, and quantity of published metadata, as revealed by regression models,
      clear shortfalls were identified with regard to anuran families, biomes, and
      categories of threat. More than 55% of these species belong to the two richest
      families, Hylidae or Leptodactylidae. The lowest percentage of species with
      described calls corresponds to the most diverse biomes, namely Atlantic Forest
      (65.1%) and Amazon (71.5%), and to the IUCN categories of threat (56.8%),
      relative to the less-than-threatened categories (74.3%). Moreover, only 52.3% of
      the species have some of its calls deposited in the main scientific sound
      collections. Our findings evidence remarkable knowledge gaps on advertisement
      calls of Brazilian anuran species, emphasizing the need of further efforts in
      standardizing and increasing the description of anuran calls for their
      application in studies of the behaviour, ecology, biogeography or taxonomy of the
      species.

PMID- 29381752
TI  - Correction: Assessing development assistance for child survival between 2000 and
      2014: A multi-sectoral perspective.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178887.].

PMID- 29381751
TI  - Molecular mechanism of inhibitory effects of bovine lactoferrin on the growth of
      oral squamous cell carcinoma.
AB  - BACKGROUND: Lactoferrin (LF), a member of the transferrin family, recently has
      been demonstrated to have anticancer effects on various cancers including oral
      squamous cell carcinoma (OSCC). However, little is known about the underlying
      mechanisms of its effects on OSCC. Therefore, we aimed to investigate the
      mechanism of the suppressive effects of bovine LF (bLF) on the growth of OSCC
      cells. METHODS: In the current study, HSC2, HSC3, HSC4 and normal human oral
      keratinocytes (RT7) cell lines were tested with bLF 1, 10, and 100 MUg/ml. The
      effects and detail mechanisms of bLF on proliferation and apoptosis of cells were
      investigated using flow cytometry and western blotting. RESULTS: We found that
      bLF (1, 10, and 100 MUg/ml) induced activation of p53, a tumor suppressor gene,
      is associated with the induction of cell cycle arrest in G1/S phase and apoptosis
      in OSCC. Moreover, bLF downregulated the phosphorylation of Akt and activated
      suppressor of cytokine signaling 3 (SOCS3), thereby attenuating multiple
      signaling pathways including mTOR/S6K and JAK/STAT3. Interestingly, we revealed
      that bLF exerted its effect selectively against HSC3 but not on RT7 via different
      effects on the phosphorylation status of NF-kappaB and Akt. CONCLUSION: This is
      the first report showing that bLF selectively suppresses proliferation through
      mTOR/S6K and JAK/STAT3 pathways and induction of apoptosis in OSCC. This study
      provides important new findings, which might be useful in the prevention and
      treatment of OSCC.

PMID- 29381753
TI  - Influence of seasonality and gestation on habitat selection by northern Mexican
      gartersnakes (Thamnophis eques megalops).
AB  - Species conservation requires a thorough understanding of habitat requirements.
      The northern Mexican gartersnake (Thamnophis eques megalops) was listed as
      threatened under the U.S. Endangered Species Act in 2014. Natural resource
      managers are interested in understanding the ecology of this subspecies to guide
      management decisions and to determine what features are necessary for habitat
      creation and restoration. Our objective was to identify habitat selection of
      northern Mexican gartersnakes in a highly managed, constructed wetland hatchery.
      We deployed transmitters on 42 individual gartersnakes and documented use of
      habitat types and selection of specific habitat features. Habitat selection was
      similar between males and females and varied seasonally. During the active season
      (March-October), gartersnakes primarily selected wetland edge habitat with
      abundant cover. Gestating females selected similar locations but with less dense
      cover. During the inactive season (November-February), gartersnakes selected
      upland habitats, including rocky slopes with abundant vegetation. These results
      of this study can help inform management of the subspecies, particularly in human
      influenced habitats. Conservation of this subspecies should incorporate a
      landscape-level approach that includes abundant wetland edge habitat with a
      mosaic of dense cover for protection and sparsely vegetated areas for basking
      connected to terrestrial uplands for overwintering.

PMID- 29381754
TI  - Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient
      elastography in HIV mono-infection.
AB  - BACKGROUND AND AIM: HIV-infected individuals are at high risk of developing
      nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease
      in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH
      remains poorly understood in HIV mono-infection. We aimed to characterize the
      prevalence and predictors of NASH in unselected HIV mono-infected patients by
      means of non-invasive diagnostic tools. METHODS: HIV-infected adults without
      significant alcohol intake or co-infection with hepatitis B or C underwent a
      routine screening program employing transient elastography (TE) with controlled
      attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH
      was diagnosed non-invasively as the coexistence of fatty liver (CAP >=248 dB/m)
      and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver
      biopsy. Predictors of NASH were determined by multivariate logistic regression
      analysis. RESULTS: 202 consecutive HIV mono-infected patients were included. NASH
      was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a
      liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH
      was higher in patients with hypertriglyceridemia (17.1%), insulin resistance
      defined by homeostasis model for assessment of insulin resistance (HOMA-IR)
      (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT
      (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95%
      CI 1.01-1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50-3.79; p<0.001) were
      independent predictors of NASH. CONCLUSIONS: NASH, diagnosed by a non-invasive
      diagnostic approach employing CK-18 and TE with CAP, is common in unselected HIV
      mono-infected individuals, particularly in the presence of insulin resistance and
      elevated ALT.

PMID- 29381755
TI  - Geographical patterns in climate and agricultural technology drive soybean
      productivity in Brazil.
AB  - The impacts of global climate change have been a worldwide concern for several
      research areas, including those dealing with resources essential to human well
      being, such as agriculture, which directly impact economic activities and food
      security. Here we evaluate the relative effect of climate (as indicated by the
      Ecological Niche Model-ENM) and agricultural technology on actual soybean
      productivity in Brazilian municipalities and estimate the future geographic
      distribution of soybeans using a novel statistical approach allowing the
      evaluation of partial coefficients in a non-stationary (Geographically Weighted
      Regression; GWR) model. We found that technology was more important than climate
      in explaining soybean productivity in Brazil. However, some municipalities are
      more dependent on environmental suitability (mainly in Southern Brazil). The
      future environmental suitability for soybean cultivation tends to decrease by up
      50% in the central region of Brazil. Meanwhile, southern-most Brazil will have
      more favourable conditions, with an increase of ca. 25% in environmental
      suitability. Considering that opening new areas for cultivation can degrade
      environmental quality, we suggest that, in the face of climate change impacts on
      soybean cultivation, the Brazilian government and producers must invest in
      breeding programmes and more general ecosystem-based strategies for adaptation to
      climate change, including the development of varieties tolerant to climate
      stress, and strategies to increase productivity and reduce costs (social and
      environmental).

PMID- 29381756
TI  - Longitudinal changes in clinical characteristics and outcomes for children using
      long-term non-invasive ventilation.
AB  - OBJECTIVES: To describe longitudinal trends in long-term non-invasive ventilation
      (NIV) use in children including changes in clinical characteristics, NIV
      technology, and outcomes. METHODS: This was a multicenter retrospective cohort of
      all children started on long-term NIV from 2005 to 2014. All children 0 to 18
      years who used NIV continuously for at least 3 months were included. Measures and
      main outcomes were: 1) Number of children starting NIV; 2) primary medical
      condition; 3) medical complexity defined by number of comorbidities, surgeries
      and additional technologies; 4) severity of sleep disordered breathing measured
      by diagnostic polysomnography; 5) NIV technology and use; 6) reasons for NIV
      discontinuation including mortality. Data were divided into equal time periods
      for analysis. RESULTS: A total of 622 children were included in the study. Median
      age at NIV initiation was 7.8 years (range 0-18 years). NIV incidence and
      prevalence increased five and three-fold over the 10-year period. More children
      with neurological and cardio-respiratory conditions started NIV over time, from
      13% (95%CI, 8%-20%) and 6% (95%CI, 3%-10%) respectively in 2005-2008 to 23%
      (95%CI, 18%-28%) and 9% (95%CI, 6%-14%, p = 0.008) in 2011-2014. Medical
      complexity and severity of the sleep-disordered breathing did not change over
      time. Overall, survival was 95%; mortality rates, however, rose from 3.4 cases
      (95% CI, 0.5-24.3) to 142.1 (95% CI 80.7-250.3, p<0.001) per 1000 children-years
      between 2005-2008 and 2011-2014. Mortality rates differed by diagnostic category,
      with higher rates in children with neurological and cardio-respiratory
      conditions. CONCLUSIONS: As demonstrated in other centers, there was a
      significant increase in NIV prevalence and incidence rate. There was no increase
      in medical complexity or severity of the breathing abnormalities of children
      receiving long-term NIV over time. The mortality rate increased over time, maybe
      attributable to increased use of NIV for children with neurological and cardio
      respiratory conditions.

PMID- 29381757
TI  - The effect of ad hominem attacks on the evaluation of claims promoted by
      scientists.
AB  - Two experiments were conducted to determine the relative impact of direct and
      indirect (ad hominem) attacks on science claims. Four hundred and thirty-nine
      college students (Experiment 1) and 199 adults (Experiment 2) read a series of
      science claims and indicated their attitudes towards those claims. Each claim was
      paired with one of the following: A) a direct attack upon the empirical basis of
      the science claim B) an ad hominem attack on the scientist who made the claim or
      C) both. Results indicate that ad hominem attacks may have the same degree of
      impact as attacks on the empirical basis of the science claims, and that
      allegations of conflict of interest may be just as influential as allegations of
      outright fraud.

PMID- 29381759
TI  - Faecal glucocorticoid metabolites and body temperature in Australian merino ewes
      (Ovis aries) during summer artificial insemination (AI) program.
AB  - Reproductive wastage is a key issue for sheep producers, both regionally and
      globally. The reproductive output of farm animals can be influenced by
      physiological and environmental factors. Rapid and reliable quantification of
      physiological stress can provide a useful tool for designing and testing on-farm
      management interventions to improve farm animal welfare and productivity. In this
      study, we quantified physiological stress non-invasively using faecal
      glucocorticoid metabolites-FGMs analysis and body temperature measurements of 15
      superovulated donor merino ewes (Ovis aries) during participation in artificial
      insemination (AI) program conducted during 2015/2016 Australian summer. We
      hypothesized that low percentage transferable embryos in donor merino ewes will
      be associated positively with higher body temperature and/or higher FGMs in these
      ewes. Temperature humidity index (THI) was calculated and found within high
      thermal stress range during the two AI trials. Overall, results showed none of
      the factors (ewe ID, AI trial no., THI or FGMs) were significant for reduced
      percentage transferrable embryos, except ewe body temperature was highly
      significant (p = 0.014). Within AI trial comparisons showed significant positive
      associations between higher FGMs and body temperature with reduced transferrable
      embryos. These results suggest that Australian merino ewes participating in
      summer AI trials can experience physiological stress. Prolonged activation of the
      stress endocrine response and high body temperature (e.g. ensued from heat
      stress) could impact on ewe reproductive output. Therefore, future research
      should apply minimally invasive physiological tools to gather baseline
      information on physiological stress in merino sheep to enable the development of
      new farm-friendly methods of managing stress.

PMID- 29381758
TI  - Insight into higher-level phylogeny of Neuropterida: Evidence from secondary
      structures of mitochondrial rRNA genes and mitogenomic data.
AB  - It is well known that the rRNA structure information is important to assist
      phylogenetic analysis through identifying homologous positions to improve
      alignment accuracy. In addition, the secondary structure of some conserved motifs
      is highly stable among distantly related taxa, which can provide potentially
      informative characters for estimating phylogeny. In this paper, we applied the
      high-throughput pooled sequencing approach to the determination of neuropteran
      mitogenomes. Four complete mitogenome sequences were obtained: Micromus angulatus
      (Hemerobiidae), Chrysoperla nipponensis (Chrysopidae), Rapisma sp. (Ithonidae),
      and Thaumatosmylus sp. (Osmylidae). This allowed us to sample more complete
      mitochondrial RNA gene sequences. Secondary structure diagrams for the complete
      mitochondrial small and large ribosomal subunit RNA genes of eleven neuropterid
      species were predicted. Comparative analysis of the secondary structures
      indicated a closer relationship of Megaloptera and Neuroptera. This result was
      congruent with the resulting phylogeny inferred from sequence alignments of all
      37 mitochondrial genes, namely the hypothesis of (Raphidioptera + (Megaloptera +
      Neuroptera)).

PMID- 29381760
TI  - Can biosecurity and local network properties predict pathogen species richness in
      the salmonid industry?
AB  - Salmonid farming in Ireland is mostly organic, which implies limited disease
      treatment options. This highlights the importance of biosecurity for preventing
      the introduction and spread of infectious agents. Similarly, the effect of local
      network properties on infection spread processes has rarely been evaluated. In
      this paper, we characterized the biosecurity of salmonid farms in Ireland using a
      survey, and then developed a score for benchmarking the disease risk of salmonid
      farms. The usefulness and validity of this score, together with farm indegree
      (dichotomized as <= 1 or > 1), were assessed through generalized Poisson
      regression models, in which the modeled outcome was pathogen richness, defined
      here as the number of different diseases affecting a farm during a year. Seawater
      salmon (SW salmon) farms had the highest biosecurity scores with a median
      (interquartile range) of 82.3 (5.4), followed by freshwater salmon (FW salmon)
      with 75.2 (8.2), and freshwater trout (FW trout) farms with 74.8 (4.5). For FW
      salmon and trout farms, the top ranked model (in terms of leave-one-out
      information criteria, looic) was the null model (looic = 46.1). For SW salmon
      farms, the best ranking model was the full model with both predictors and their
      interaction (looic = 33.3). Farms with a higher biosecurity score were associated
      with lower pathogen richness, and farms with indegree > 1 (i.e. more than one
      fish supplier) were associated with increased pathogen richness. The effect of
      the interaction between these variables was also important, showing an
      antagonistic effect. This would indicate that biosecurity effectiveness is
      achieved through a broader perspective on the subject, which includes a
      minimization in the number of suppliers and hence in the possibilities for
      infection to enter a farm. The work presented here could be used to elaborate
      indicators of a farm's disease risk based on its biosecurity score and indegree,
      to inform risk-based disease surveillance and control strategies for private and
      public stakeholders.

PMID- 29381761
TI  - Using arborescences to estimate hierarchicalness in directed complex networks.
AB  - Complex networks are a useful tool for the understanding of complex systems. One
      of the emerging properties of such systems is their tendency to form hierarchies:
      networks can be organized in levels, with nodes in each level exerting control on
      the ones beneath them. In this paper, we focus on the problem of estimating how
      hierarchical a directed network is. We propose a structural argument: a network
      has a strong top-down organization if we need to delete only few edges to reduce
      it to a perfect hierarchy-an arborescence. In an arborescence, all edges point
      away from the root and there are no horizontal connections, both characteristics
      we desire in our idealization of what a perfect hierarchy requires. We test our
      arborescence score in synthetic and real-world directed networks against the
      current state of the art in hierarchy detection: agony, flow hierarchy and global
      reaching centrality. These tests highlight that our arborescence score is
      intuitive and we can visualize it; it is able to better distinguish between
      networks with and without a hierarchical structure; it agrees the most with the
      literature about the hierarchy of well-studied complex systems; and it is not
      just a score, but it provides an overall scheme of the underlying hierarchy of
      any directed complex network.

PMID- 29381762
TI  - A user-friendly tool to evaluate the effectiveness of no-take marine reserves.
AB  - Marine reserves are implemented to achieve a variety of objectives, but are
      seldom rigorously evaluated to determine whether those objectives are met. In the
      rare cases when evaluations do take place, they typically focus on ecological
      indicators and ignore other relevant objectives such as socioeconomics and
      governance. And regardless of the objectives, the diversity of locations,
      monitoring protocols, and analysis approaches hinder the ability to compare
      results across case studies. Moreover, analysis and evaluation of reserves is
      generally conducted by outside researchers, not the reserve managers or users,
      plausibly thereby hindering effective local management and rapid response to
      change. We present a framework and tool, called "MAREA", to overcome these
      challenges. Its purpose is to evaluate the extent to which any given reserve has
      achieved its stated objectives. MAREA provides specific guidance on data
      collection and formatting, and then conducts rigorous causal inference analysis
      based on data input by the user, providing real-time outputs about the
      effectiveness of the reserve. MAREA's ease of use, standardization of state-of
      the-art inference methods, and ability to analyze marine reserve effectiveness
      across ecological, socioeconomic, and governance objectives could dramatically
      further our understanding and support of effective marine reserve management.

PMID- 29381764
TI  - Potential disruption of seed dispersal in the absence of a native Kauai thrush.
AB  - Hawaii has experienced a catastrophic decline in frugivorous native birds coupled
      with the introduction of non-native species. Puaiohi (Myadestes palmeri), a
      critically endangered thrush, is the sole extant native songbird capable of
      dispersing fleshy fruited plants in the rainforest of Kauai island, Hawaii. As
      this species has declined to occupy a small proportion of its original range, a
      suite of largely omnivorous non-native birds have been introduced to this region,
      including the common and widespread Japanese White-eye (Zosterops japonicus).
      This reshuffling of the bird community could have long-term implications for
      plant community composition if introduced birds incompletely replace the
      ecological role of native species. The objective of this study was to evaluate
      the potential consequences of the local extirpation of Puaiohi for seed
      dispersal. Specifically, we compared the diet of Puaiohi and Japanese White-eye,
      vegetation characteristics, and seed rain at sites with and without Puaiohi in
      the Na Pali-Kona Forest Reserve on the island of Kauai. We found high overlap in
      the composition of seeds consumed by the two bird species, but differences in the
      characteristics of seeds consumed; Japanese White-eye appeared more likely to
      consume smaller seeded species compared with Puaiohi. Sites with Puaiohi received
      substantially higher seed rain during the study period, despite no significant
      differences in overall fruit abundance. Our results suggest that non-native birds
      are unlikely to completely replace the seed dispersal services provided by
      Puaiohi. If Puaohi continue to be rare and range restricted, we predict a shift
      in plant community composition through an increase in non-native and small-seeded
      plants, and possible dispersal failure of other native species. Our findings lend
      further support to efforts to conserve Puaiohi across its current and former
      range, and to consider introductions to other suitable areas to ensure the
      persistence not only of the species and but also its functional role in Hawaii's
      montane ecosystems.

PMID- 29381763
TI  - A new mechanism of interferon's antiviral action: Induction of autophagy,
      essential for paramyxovirus replication, is inhibited by the interferon
      stimulated gene, TDRD7.
AB  - The interferon (IFN) system represents the first line of defense against a wide
      range of viruses. Virus infection rapidly triggers the transcriptional induction
      of IFN-beta and IFN Stimulated Genes (ISGs), whose protein products act as viral
      restriction factors by interfering with specific stages of virus life cycle, such
      as entry, transcription, translation, genome replication, assembly and egress.
      Here, we report a new mode of action of an ISG, IFN-induced TDRD7 (tudor domain
      containing 7) inhibited paramyxovirus replication by inhibiting autophagy. TDRD7
      was identified as an antiviral gene by a high throughput screen of an ISG shRNA
      library for blocking IFN's protective effect against Sendai virus (SeV)
      replication. The antiviral activity of TDRD7 against SeV, human parainfluenza
      virus 3 and respiratory syncytial virus was confirmed by its genetic ablation or
      ectopic expression in several types of mouse and human cells. TDRD7's antiviral
      action was mediated by its ability to inhibit autophagy, a cellular catabolic
      process which was robustly induced by SeV infection and required for its
      replication. Mechanistic investigation revealed that TDRD7 interfered with the
      activation of AMP-dependent kinase (AMPK), an enzyme required for initiating
      autophagy. AMPK activity was required for efficient replication of several
      paramyxoviruses, as demonstrated by its genetic ablation or inhibition of its
      activity by TDRD7 or chemical inhibitors. Therefore, our study has identified a
      new antiviral ISG with a new mode of action.

PMID- 29381766
TI  - Analysis of motility in multicellular Chlamydomonas reinhardtii evolved under
      predation.
AB  - The advent of multicellularity was a watershed event in the history of life, yet
      the transition from unicellularity to multicellularity is not well understood.
      Multicellularity opens up opportunities for innovations in intercellular
      communication, cooperation, and specialization, which can provide selective
      advantages under certain ecological conditions. The unicellular alga
      Chlamydomonas reinhardtii has never had a multicellular ancestor yet it is
      closely related to the volvocine algae, a clade containing taxa that range from
      simple unicells to large, specialized multicellular colonies. Simple
      multicellular structures have been observed to evolve in C. reinhardtii in
      response to predation or to settling rate-based selection. Structures formed in
      response to predation consist of individual cells confined within a shared
      transparent extracellular matrix. Evolved isolates form such structures
      obligately under culture conditions in which their wild type ancestors do not,
      indicating that newly-evolved multicellularity is heritable. C. reinhardtii is
      capable of photosynthesis, and possesses an eyespot and two flagella with which
      it moves towards or away from light in order to optimize input of radiant energy.
      Motility contributes to C. reinhardtii fitness because it allows cells or
      colonies to achieve this optimum. Utilizing phototaxis to assay motility, we
      determined that newly evolved multicellular strains do not exhibit significant
      directional movement, even though the flagellae of their constituent unicells are
      present and active. In C. reinhardtii the first steps towards multicellularity in
      response to predation appear to result in a trade-off between motility and
      differential survivorship, a trade-off that must be overcome by further genetic
      change to ensure long-term success of the new multicellular organism.

PMID- 29381767
TI  - Correction: The promoter region of lapA and its transcriptional regulation by Fis
      in Pseudomonas putida.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0185482.].

PMID- 29381765
TI  - Differential miRNA expression in B cells is associated with inter-individual
      differences in humoral immune response to measles vaccination.
AB  - BACKGROUND: MicroRNAs are important mediators of post-transcriptional regulation
      of gene expression through RNA degradation and translational repression, and are
      emerging biomarkers of immune system activation/response after vaccination.
      METHODS: We performed Next Generation Sequencing (mRNA-Seq) of intracellular
      miRNAs in measles virus-stimulated B and CD4+ T cells from high and low antibody
      responders to measles vaccine. Negative binomial generalized estimating equation
      (GEE) models were used for miRNA assessment and the DIANA tool was used for
      gene/target prediction and pathway enrichment analysis. RESULTS: We identified a
      set of B cell-specific miRNAs (e.g., miR-151a-5p, miR-223, miR-29, miR-15a-5p,
      miR-199a-3p, miR-103a, and miR-15a/16 cluster) and biological processes/pathways,
      including regulation of adherens junction proteins, Fc-receptor signaling
      pathway, phosphatidylinositol-mediated signaling pathway, growth factor signaling
      pathway/pathways, transcriptional regulation, apoptosis and virus-related
      processes, significantly associated with neutralizing antibody titers after
      measles vaccination. No CD4+ T cell-specific miRNA expression differences between
      high and low antibody responders were found. CONCLUSION: Our study demonstrates
      that miRNA expression directly or indirectly influences humoral immunity to
      measles vaccination and suggests that B cell-specific miRNAs may serve as useful
      predictive biomarkers of vaccine humoral immune response.

PMID- 29381768
TI  - Soil attributes drive nest-site selection by the campo miner Geositta
      poeciloptera.
AB  - Substrate type is a key-factor in nest-site selection and nest architecture of
      burrowing birds. However, little is known about which factors drive nest-site
      selection for these species, especially in the tropics. We studied the influence
      of soil attributes on nest-site selection by the campo miner Geositta
      poeciloptera, an open grassland bird that builds its nests within soil cavities.
      For all nests found, we measured the depth of the nest cavity and the resistance
      of the soil to penetration, and identified the soil horizon in which the nest was
      located. In soil banks with nests, we collected soil samples for granulometric
      analysis around each nest cavity, while in soil banks without nests we collected
      these samples at random points. From 43 nests found, 86% were located in the
      deeper soil horizons (C-horizon), and only 14% in the shallower horizons (B
      horizon). Granulometric analysis showed that the C-horizons possessed a high
      similar granulometric composition, with high silt and low clay contents. These
      characteristics are associated with a low degree of structural development of the
      soil, which makes it easier to excavate. Contrarily, soil resistance to
      penetration does not seem to be an important criterion for nest site selection,
      although nests in more resistant the soils tend to have shallower nest cavities.
      Among the soil banks analyzed, 40% of those without cavities possessed a larger
      proportion of B-horizon relative to the C-horizon, and their texture was more
      clayey. On the other hand, almost all soil banks containing nest cavities had a
      larger C-horizon and a silty texture, indicating that soil attributes drive nest
      site selection by G. poeciloptera. Thus, we conclude that the patchy distribution
      of G. poeciloptera can attributed to the infrequent natural exposure of the C
      horizon in the tropical region, where well developed, deep and permeable soils
      are more common.

PMID- 29381769
TI  - Correction: DNA extraction replicates improve diversity and compositional
      dissimilarity in metabarcoding of eukaryotes in marine sediments.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0179443.].

PMID- 29381771
TI  - Correction: What is in your cup of tea? DNA Verity Test to characterize black and
      green commercial teas.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178262.].

PMID- 29381770
TI  - The conserved basic residues and the charged amino acid residues at the alpha
      helix of the zinc finger motif regulate the nuclear transport activity of triple
      C2H2 zinc finger proteins.
AB  - Zinc finger (ZF) motifs on proteins are frequently recognized as a structure for
      DNA binding. Accumulated reports indicate that ZF motifs contain nuclear
      localization signal (NLS) to facilitate the transport of ZF proteins into
      nucleus. We investigated the critical factors that facilitate the nuclear
      transport of triple C2H2 ZF proteins. Three conserved basic residues (hot spots)
      were identified among the ZF sequences of triple C2H2 ZF proteins that reportedly
      have NLS function. Additional basic residues can be found on the alpha-helix of
      the ZFs. Using the ZF domain (ZFD) of Egr-1 as a template, various mutants were
      constructed and expressed in cells. The nuclear transport activity of various
      mutants was estimated by analyzing the proportion of protein localized in the
      nucleus. Mutation at any hot spot of the Egr-1 ZFs reduced the nuclear transport
      activity. Changes of the basic residues at the alpha-helical region of the second
      ZF (ZF2) of the Egr-1 ZFD abolished the NLS activity. However, this activity can
      be restored by substituting the acidic residues at the homologous positions of
      ZF1 or ZF3 with basic residues. The restored activity dropped again when the hot
      spots at ZF1 or the basic residues in the alpha-helix of ZF3 were mutated. The
      variations in nuclear transport activity are linked directly to the binding
      activity of the ZF proteins with importins. This study was extended to other
      triple C2H2 ZF proteins. SP1 and KLF families, similar to Egr-1, have charged
      amino acid residues at the second (alpha2) and the third (alpha3) positions of
      the alpha-helix. Replacing the amino acids at alpha2 and alpha3 with acidic
      residues reduced the NLS activity of the SP1 and KLF6 ZFD. The reduced activity
      can be restored by substituting the alpha3 with histidine at any SP1 and KLF6
      ZFD. The results show again the interchangeable role of ZFs and charge residues
      in the alpha-helix in regulating the NLS activity of triple C2H2 ZF proteins.

PMID- 29381772
TI  - Comparison of outcomes in hematological malignancies treated with haploidentical
      or HLA-identical sibling hematopoietic stem cell transplantation following
      myeloablative conditioning: A meta-analysis.
AB  - PURPOSE: Haploidentical and human leukocyte antigen (HLA)-identical sibling
      hematopoietic stem transplantation are two main ways used in allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). In recent years, remarkable
      progress has been made in haploidentical allo-HSCT (HID-SCT), and some
      institutions found HID-SCT had similar outcomes as HLA-identical sibling allo
      HSCT (ISD-SCT). To clarify if HID-SCT has equal effects to ISD-SCT in hematologic
      malignancies, we performed this meta-analysis. METHODS: Relevant articles
      published prior to February 2017 were searched on PubMed. Two reviewers assessed
      the quality of the included studies and extracted data independently. Odds ratio
      (OR) and 95% confidence intervals (CIs) were calculated for statistical analysis.
      RESULTS: Seven studies including 1919 patients were included. The rate of
      platelet engraftment is significantly lower after HID-SCT versus ISD-SCT while
      there is no difference in neutrophil engraftment (OR = 2.58, 95% CI = 1.70-3.93,
      P < 0.00001). The risk of acute graft-versus-host disease (GVHD) is significantly
      higher after HID-SCT versus ISD-SCT (OR = 1.88, 95% CI = 1.42-2.49, P < 0.00001),
      but the relapse rate is lower in HID-SCT group (OR = 0.70, 95% CI = 0.55-0.90, P
      = 0.005). The incidence rates of overall survival (OS) and disease-free
      survival/leukemia-free survival/relapse-free survival (DFS/LFS/RFS) after ISD-SCT
      are all significantly superior to HID-SCT (OR = 1.32, 95% CI = 1.08-1.62, P =
      0.006; OR = 1.25, 95% CI = 1.03-1.52, P = 0.02). There is no significant
      difference in transplantation related mortality (TRM) rate after HID-SCT and ISD
      SCT. CONCLUSION: After myeloablative conditioning, patients receiving ISD-SCT
      have a faster engraftment, lower acute GVHD and longer life expectancy compared
      to HID-SCT with GVHD prophylaxis (cyclosporine A, methotrexate, mycophenolate
      mofetil and antithymoglobulin; CsA + MTX + MMF + ATG). Currently, HID-SCT with
      GVHD prophylaxis (CsA + MTX + MMF + ATG) may not replace ISD-SCT when HLA
      identical sibling donor available.

PMID- 29381774
TI  - Correction: Cognitive function in multiple sclerosis improves with
      telerehabilitation: Results from a randomized controlled trial.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177177.].

PMID- 29381773
TI  - Association of circulating CTRP9 with soluble adhesion molecules and inflammatory
      markers in patients with type 2 diabetes mellitus and coronary artery disease.
AB  - C1q/TNF-related protein 9 (CTRP9) is a paralogue of adiponectin with known
      favorable effects on lipid and glucose metabolism. A potential role of CTRP9 for
      regulation of endothelium function has been suggested by previous studies.
      However, no studies have examined the relation between serum CTRP9 levels and
      adhesion molecules in patients with type 2 diabetes mellitus (T2DM) and coronary
      artery disease (CAD). The present study was conducted on 337 subjects who
      underwent coronary angiography and were categorized into four groups according to
      the presence of CAD and T2DM (control, CAD, T2DM and CAD+T2DM). Serum levels of
      CTRP9, adiponectin, sICAM-1, sVCAM-1, sE-Selectin, IL-6 and TNF-alpha were
      measured. It was found that the circulating CTRP9 levels were independently
      associated with increased risk of CAD and T2DM in addition to elevated levels of
      serum CTRP9 in CAD, T2DM and CAD+T2DM groups. A significant association of serum
      CTRP9 levels with adhesion molecules in CAD and T2DM patients as well as serum
      TNF-alpha levels in CAD individuals was noted. A significant relation between the
      circulating levels of CTRP9 and HOMA-IR in T2DM subjects was also observed. The
      results revealed increased circulating levels of CTRP9 in T2DM and CAD
      individuals which suggests a compensatory response to insulin resistance,
      inflammatory milieu and endothelial dysfunction; however, more studies are needed
      to confirm this.

PMID- 29381775
TI  - Molecular elucidation of a new allelic variation at the Sg-5 gene associated with
      the absence of group A saponins in wild soybean.
AB  - In soybean, triterpenoid saponin is one of the major secondary metabolites and is
      further classified into group A and DDMP saponins. Although they have known
      health benefits for humans and animals, acetylation of group A saponins causes
      bitterness and gives an astringent taste to soy products. Therefore, several
      studies are being conducted to eliminate acetylated group A saponins. Previous
      studies have isolated and characterized the Sg-5 (Glyma.15g243300) gene, which
      encodes the cytochrome P450 72A69 enzyme and is responsible for soyasapogenol A
      biosynthesis. In this study, we elucidated the molecular identity of a novel
      mutant of Glycine soja, 'CWS5095'. Phenotypic analysis using TLC and LC-PDA/MS/MS
      showed that the mutant 'CWS5095' did not produce any group A saponins.
      Segregation analysis showed that the absence of group A saponins is controlled by
      a single recessive allele. The locus was mapped on chromosome 15 (4.3 Mb) between
      Affx-89193969 and Affx-89134397 where the previously identified Glyma.15g243300
      gene is positioned. Sequence analysis of the coding region for the
      Glyma.15g243300 gene revealed the presence of four SNPs in 'CWS5095' compared to
      the control lines. One of these four SNPs (G1127A) leads to the amino acid change
      Arg376Lys in the EXXR motif, which is invariably conserved among the CYP450
      superfamily proteins. Co-segregation analysis showed that the missense mutation
      (Arg376Lys) was tightly linked with the absence of group A saponins in 'CWS5095'.
      Even though Arg and Lys have similar chemical features, the 3D modelled protein
      structure indicates that the replacement of Arg with Lys may cause a loss-of
      function of the Sg-5 protein by inhibiting the stable binding of a heme cofactor
      to the CYP72A69 apoenzyme.

PMID- 29381776
TI  - Effects of low-protein diets on acute phase proteins and heat shock protein 70
      responses, and growth performance in broiler chickens under heat stress
      condition.
AB  - A study with a 4 * 2 factorial arrangement was conducted to investigate the
      effects of 4 dietary protein levels and 2 environmental conditions on acute phase
      proteins (APP), brain heat shock protein (HSP) 70 density, and growth performance
      of broiler chickens. Day-old broiler chicks (Cobb 500) were fed isocaloric diets
      but with various levels of crude protein (CP), namely, (1) 21.0 and 19.0% CP in
      starter and finisher diets, respectively (control), (2) 19.5 and 17.5% CP in
      starter and finisher diets, respectively (Diet A), (3) 18.0 and 16.0% CP in
      starter and finisher diets, respectively (Diet B), and (4) 16.5 and 14.5% CP in
      starter and finisher diets, respectively (Diet C). Equal numbers of birds from
      each diet were subjected to either 23+/-1 degrees C throughout or 33+/-1 degrees
      C for 6 h per d from 22 to 35 d of age. From d 1 to 21, feed intake (FI) and
      weight gain (WG) decreased linearly (P = 0.021 and P = 0.009, respectively), as
      CP level was reduced. During the heat treatment period (d 22 to 35), there were
      significant (P = 0.04) diet * heat treatment interactions for FCR. Diet had no
      effect on FCR among the unheated birds, but the ratio increased linearly (P =
      0.007) as dietary CP level decreased. Irrespective of ambient temperature, there
      was a significant linear decrease in FI (P = 0.032) and WG (P < 0.001) as dietary
      CP level decreased. Low-CP diets improved the survivability of heat-stressed
      broilers when compared to those fed control diets. Low-CP diets linearly
      decreased (P < 0.01) APP (ovotransferrin and alpha-acid glycoprotein) responses.
      Both APP and HSP 70 reactions were elevated following heat treatment. In
      conclusion, feeding broilers with low-CP diets adversely affect the growth
      performance of broilers under heat stress condition. However, low-CP diets were
      beneficial in improving the survivability. Because APP are involved in the
      restoration of homeostasis, the adverse effect of low-CP diet on the synthesis of
      these proteins could be of concern.

PMID- 29381777
TI  - The AKT/BCL-2 Axis Mediates Survival of Uterine Leiomyoma in a Novel 3D Spheroid
      Model.
AB  - A deeper understanding of the pathways that drive uterine leiomyoma (ULM) growth
      and survival requires model systems that more closely mimic the in vivo tumors.
      This would provide new insights into developing effective therapeutic strategies
      for these common benign tumors of childbearing-aged women. In this study, we
      examined the role of BCL-2 in mediating ULM survival in the context of increased
      protein kinase B (AKT) and oxidative stress using a three-dimensional (3D),
      spheroid-based model that more closely resembles the native ULM tumor
      microenvironment. Human primary cells from matched myometrium (MM) and ULM
      tissues were used to establish spheroid cultures in vitro. Histological and
      immunohistochemical methods were used to assess the spheroid architecture and
      characteristics. Viability assays for 3D cultures were used to evaluate their
      response to BH3 mimetics and the superoxide inducer, paraquat (PQ). Primary MM
      and ULM cells formed spheroids in culture. Notably, ULM spheroids exhibited low
      proliferation, increased oxidative stress, and secretion of interstitial
      collagen. Knockdown studies revealed that AKT sustained BCL-2 expression in ULM.
      The targeting of BCL-2 with BH3 mimetics effectively reduced viability and
      induced apoptosis in a subset of ULM spheroids. ULM spheroids that did not
      respond to BH3 mimetics alone responded to combination treatment with PQ. In
      conclusion, BCL-2 mediates AKT survival of ULM, providing compelling evidence for
      further evaluation of BH3 mimetics for ULM treatment. ULM spheroids recapitulated
      intrinsic features of the native ULM tumor microenvironment and can be used as a
      model for preclinical testing of potential therapeutic options for ULM.

PMID- 29381779
TI  - Aging and Demographic Transition in Ghana: State of the Elderly and Emerging
      Issues.
AB  - Although the population of Ghana is young and generally youthful, there is
      evidence of rapid increases in the size of the elderly cohort. Although
      demographic projections estimate that the proportion of the population younger
      than 15 years will experience continuous decline overtime due in part to decline
      in fertility, the rise in the elderly population is expected to also continue due
      to declining mortality rates resulting in longevity. Unfortunately, the growth in
      the elderly proportion of the population is occurring at the same time
      traditional systems of protection and care for the aged are breaking down on
      account of urbanization, socioeconomic development, and globalization. This has
      implications for public policy and the overall wellbeing of the elderly. This
      paper provides a snapshot overview of the demographic dynamics of Ghana focusing
      on the characteristics of aging, the challenges confronting the elderly, policy
      interventions, and gaps, as well as some pertinent issues including emerging
      research that are shaping deliberations about the elderly in the country.

PMID- 29381780
TI  - X-Linked Hypophosphatemia and FGF23-Related Hypophosphatemic Diseases: Prospect
      for New Treatment.
AB  - Phosphate plays essential roles in many biological processes, and the serum
      phosphate level is tightly controlled. Chronic hypophosphatemia causes impaired
      mineralization of the bone matrix and results in rickets and osteomalacia.
      Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates
      phosphate metabolism. FGF23 excess induces hypophosphatemia via impaired
      phosphate reabsorption in the renal proximal tubules and decreased phosphate
      absorption in the intestines. There are several types of genetic and acquired
      FGF23-related hypophosphatemic diseases. Among these diseases, X-linked
      hypophosphatemia (XLH), which is caused by inactivating mutations in the
      phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, is the most
      prevalent form of genetic FGF23-related hypophosphatemic rickets. Another
      clinically relevant form of FGF23-related hypophosphatemic disease is tumor
      induced osteomalacia (TIO), a paraneoplastic syndrome associated with FGF23
      producing tumors. A combination of active vitamin D and phosphate salts is the
      current medical therapy used to treat patients with XLH and inoperative TIO.
      However, this therapy has certain efficacy- and safety-associated limitations.
      Several measures to inhibit FGF23 activity have been considered as possible new
      treatments for FGF23-related hypophosphatemic diseases. In particular, a
      humanized monoclonal antibody for FGF23 (burosumab) is a promising treatment in
      patients with XLH and TIO. This review will focus on the phosphate metabolism and
      the pathogenesis and treatment of FGF23-related hypophosphatemic diseases.

PMID- 29381778
TI  - Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission
      Within the Cerebellar Cortex.
AB  - Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the
      adult rodent cerebellum, the best-characterized action of estradiol is to enhance
      glutamatergic signaling. However, the mechanisms by which estradiol promotes
      glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we
      found that estrogen receptor activation of metabotropic glutamate receptor type
      1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell
      synapse. The blockade of local estrogen synthesis within the cerebellum results
      in a diminution of glutamatergic neurotransmission. Correspondingly, decreased
      estrogen availability via gonadectomy or blockade of aromatase activity
      negatively affects locomotor performance. These data indicate that locally
      derived, and not just gonad-derived, estrogens affect cerebellar physiology and
      function. In addition, estrogens were found to facilitate parallel fiber-Purkinje
      cell synaptic transmission in both sexes. As such, the actions of estradiol to
      support cerebellar neurotransmission and cerebellum-based behaviors might be
      fundamental to understanding the normal processing of activity within the
      cerebellar cortex.

PMID- 29381781
TI  - Pharmacokinetics of florfenicol in turkey plasma, lung tissue, and pulmonary
      epithelial lining fluid after single oral bolus or continuous administration in
      the drinking water.
AB  - Florfenicol (FF) is registered for treatment of bovine and swine respiratory
      diseases. Although, turkeys often suffer from bacterial respiratory tract
      infections, there is no registered formulation based on FF for poultry available
      in Europe. The aim of this study was to evaluate the pharmacokinetic behavior of
      FF in turkeys in plasma, lung tissue, and pulmonary epithelial lining fluid
      (PELF).The concentration and pharmacokinetic characteristics of FF in plasma,
      lung tissue, and PELF in turkeys were determined, either after a single oral
      bolus (30 mg/kg body weight, BW) or during and after continuous drinking water
      medication (30 mg/kg BW/d for 5 d). Plasma, lung tissue, and PELF samples were
      collected at different intervals after administration, and FF was quantified by
      liquid chromatography-tandem mass spectrometry. After single bolus
      administration, FF was rapidly absorbed in plasma (the time to maximum
      concentration, tmax, was 1.02 h) and distributed to the respiratory tract (mean
      tmax = 1.00 h). The mean t1/2el in plasma and lung tissue was similar, around 6
      h, whereas it was slightly higher in PELF, namely, 8.7 hours. After oral bolus
      dosing, the mean maximum concentration in plasma was twice as high as in the lung
      tissue, 4.26 MUg/mL and 2.64 MUg/g, respectively, while in PELF it was much
      lower, 0.39 MUg/mL. During continuous drinking water medication, lung FF
      concentrations were slightly higher than plasma concentrations, with lung/plasma
      ratios of 2.01 and 1.27 after 24 h and 72 h, respectively. FF was not detected in
      PELF during continuous drinking water medication.

PMID- 29381782
TI  - Pathway of Maternal Serotonin to the Human Embryo and Fetus.
AB  - Serotonin [5-hydroxytryptamine (5-HT)] is essential to intrauterine development,
      but its source is debated. We used immunocytochemistry to gauge 5-HT, its
      biosynthetic enzyme tryptophan hydroxylase 1 (TPH1); an importer (serotonin
      transporter, 5-HTT/SERT/SLC6A); other transporters [P-glycoprotein 1 (P
      gp/ABCB1), OCT3/SLC22A3, and gap junction connexin-43]; and the 5-HT degradative
      enzyme monoamine oxidase A (MAOA) in sections of placentas. In humans, 5-HT was
      faintly stained only in first-trimester trophoblasts, whereas TPH1 was not seen
      at any stage. SERT was expressed in syncytiotrophoblasts and, more strongly, in
      cytotrophoblasts. MAOA was prominent in syncytiotrophoblasts, OCT3 and gap
      junctions were stained in cytotrophoblasts, and P-gp was present at the apical
      surfaces of both epithelia. 5-HT added to cultured placental explants accumulated
      in the trophoblast epithelium and reached the villus core vessels. Trophoblast
      uptake was blocked by the SERT inhibitor escitalopram. Inhibition of gap
      junctions with heptanol prevented the accumulation of 5-HT in cytotrophoblasts,
      whereas blocking OCT3 with decynium-22 and P-gp with mitotane led to its
      accumulation in cytotrophoblasts. Reducing 5-HT destruction by inhibiting MAOA
      with clorgyline increased the accumulation of 5-HT throughout the villus. In the
      mouse fetus, intravascular platelets stained prominently for 5-HT at day 13.5,
      whereas the placenta and yolk sac endoderm were both negative. TPH1 was not
      detected, but SERT was prominent in these mouse tissues. We conclude that
      serotonin is conveyed from the maternal blood stream through
      syncytiotrophoblasts, cytotrophoblasts and the villus core to the fetus through a
      physiological pathway that involves at least SERT, gap junctions, P-gp, OCT3, and
      MAOA.

PMID- 29381783
TI  - Survival and Transstadial Persistence of Trypanosoma cruzi in the bed bug
      (Hemiptera: Cimicidae).
AB  - Bed bug populations are increasing around the world at an alarming rate and have
      become a major public health concern. The appearance of bed bug populations in
      areas where Chagas disease is endemic raises questions about the role of these
      insects in the transmission of Trypanosoma cruzi, the etiological agent of the
      disease. In a series of laboratory evaluations, bed bug adults and nymphs were
      experimentally fed with T. cruzi-infected blood to assess the ability of T. cruzi
      to survive inside the bed bug and throughout the insect's molting process. Live
      T. cruzi were observed in gut contents of experimentally infected bed bug adults
      via light microscopy and the identity of the parasite was confirmed via
      polymerase chain reaction analysis. T. cruzi persisted at least 97-d
      postinfection in adult bed bugs. Nymphal stage bed bugs that were infected with
      T. cruzi maintained the parasite after molting, indicating that transstadial
      passage of T. cruzi in bed bugs took place. This report provides further evidence
      of acquisition, maintenance, and for the first time, transstadial persistence of
      T. cruzi in bed bugs.

PMID- 29381784
TI  - Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice.
AB  - We previously reported a substantial correlation between serum parathyroid
      hormone (PTH) levels and the myeloma response to proteasome inhibition that
      suggests a crucial role for the PTH receptor 1 system in the control of myeloma
      tumor growth. While investigating the role of PTH in the antimyeloma effect, we
      observed the recovery of serum PTH levels after thyroparathyroidectomy (TPTX).
      Although the presence of thymus-derived PTH has been reported previously, the
      existence or role of thymic PTH in the serum remains controversial. Here, TPTX
      was performed in 8- to 12-week-old C57BL/KaLwRij mice to delineate the potential
      source(s) for the recovery of serum PTH. Immediately after TPTX, the expected
      loss of measurable serum PTH was observed. Serum PTH levels recovered 3 to 4
      weeks after TPTX. Thirteen endocrine organs from mice with recovered serum PTH
      were examined. The thymus from control mice expressed measurable and detectable
      Pth transcripts; however, the Pth transcript level was substantially elevated in
      tissue from TPTX mice. Western blot analysis of the thymus demonstrated a
      reproducible and distinct PTH band in thymus tissue that was significantly
      increased after TPTX. To directly confirm the identity of the distinct PTH band,
      immunoprecipitated proteins were isolated and subjected to tandem mass
      spectrometry. After fragmentation and direct peptide sequencing, PTH peptides
      PTH(1-13) and PTH(54-70), diagnostic for PTH, were identified. These data
      demonstrate that the murine thymus produces PTH and that after TPTX the thymus
      becomes the major source of serum PTH, compensating for the loss of the
      parathyroid glands and returning circulating PTH levels to normal.

PMID- 29381785
TI  - Response patterns and intra-dyadic factors related to compliance with ecological
      momentary assessment among mothers and children.
AB  - Ecological momentary assessment (EMA) is a real-time sampling strategy that may
      address limitations in health research, such as the inability to examine how
      processes unfold on a daily basis. However, EMA studies are prone to limited data
      availability due to difficulties in implementing sophisticated protocols and
      systematic non-compliance with prompts, resulting in biased estimates and limited
      statistical power. The objectives of this study were to describe the availability
      of data, to examine response patterns, and to analyze factors related to EMA
      prompt compliance in a dyadic EMA study with mothers and children. Participants
      (N = 404) each received up to eight EMA prompts (i.e., audible pings) per day for
      a total of 7 days. Each EMA survey consisted of items assessing affect, perceived
      stress, and social context. Participants responded to approximately 80% (range:
      3.4%-100%) of prompted EMA surveys, and completed 92.6% of surveys once started.
      Mothers and children identifying as Hispanic, as well as mothers in lower-income
      households, were less likely to comply with any given EMA prompt. Participant
      dyads were more likely to comply with prompts when they were together.
      Understanding factors related to systematic EMA prompt non-compliance is an
      important step to reduce the likelihood of biased estimates and improve
      statistical power. Socioeconomic factors may impede mothers' compliance with EMA
      protocols. Furthermore, mothers' presence and involvement may enhance children's
      compliance with EMA protocols.

PMID- 29381786
TI  - Evaluating the effectiveness of behavior change techniques in health-related
      behavior: a scoping review of methods used.
AB  - Behavior change interventions typically contain multiple potentially active
      components: behavior change techniques (BCTs). Identifying which specific BCTs or
      BCT combinations have the potential to be effective for a given behavior in a
      given context presents a major challenge. The aim of this study was to review the
      methods that have been used to identify effective BCTs for given behaviors in
      given contexts and evaluate their strengths and limitations. A scoping review was
      conducted of studies that had sought to identify effective BCTs. Articles
      referring to "behavio(u)r change technique(s)" in the abstract/text were located,
      and ones that involved identification of effective BCTs were selected. The
      methods reported were coded. The methods were analyzed in general terms using
      "PASS" criteria: Practicability (facility to apply the method appropriately),
      Applicability (facility to generalize from findings to contexts and populations
      of interest), Sensitivity (facility to identify effective BCTs), and Specificity
      (facility to rule out ineffective BCTs). A sample of 10% of the studies reviewed
      was then evaluated using these criteria to assess how far the strengths and
      limitations identified in principle were borne out in practice. One hundred and
      thirty-five studies were identified. The methods used in those studies were
      experimental manipulation of BCTs, observational studies comparing outcomes in
      the presence or absence of BCTs, meta-analyses of BCT comparisons, meta
      regressions evaluating effect sizes with and without specific BCTs, reviews of
      BCTs found in effective interventions, and meta-classification and regression
      trees. The limitations of each method meant that only weak conclusions could be
      drawn regarding the effectiveness of specific BCTs or BCT combinations. Methods
      for identifying effective BCTs linked to target behavior and context all have
      important inherent limitations. A strategy needs to be developed that can
      systematically combine the strengths of the different methods and that can link
      these constructs in an ontology of behavior change interventions.

PMID- 29381787
TI  - Red meat consumption and risk of cardiovascular diseases-is increased iron load a
      possible link?
AB  - Background: High iron load and red meat consumption could increase the risk of
      cardiovascular diseases (CVDs). As red meat is the main source of heme iron,
      which is in turn a major determinant of increased iron load, adverse
      cardiometabolic effects of meat consumption could be mediated by increased iron
      load. Objective: The object of the study was to assess whether associations
      between red meat consumption and CVD risk are mediated by iron load in a
      population-based human study. Design: We evaluated relations between red meat
      consumption, iron load (plasma ferritin), and risk of CVD in the prospective EPIC
      Heidelberg Study using a case-cohort sample including a random subcohort (n =
      2738) and incident cases of myocardial infarction (MI, n = 555), stroke (n =
      513), and CVD mortality (n = 381). Following a 4-step mediation analysis,
      associations between red meat consumption and iron load, red meat consumption and
      CVD risk, and iron load and CVD risk were assessed by multivariable regression
      models before finally testing to which degree associations between red meat
      consumption and CVD risk were attenuated by adjustment for iron status. Results:
      Red meat consumption was significantly positively associated with ferritin
      concentrations and MI risk [HR per 50 g daily intake: 1.18 (95% CI: 1.05, 1.33)],
      but no significant associations with stroke risk and CVD mortality were observed.
      While direct associations between ferritin concentrations and MI risk as well as
      CVD mortality were significant in age- and sex-adjusted Cox regression models,
      these associations were substantially attenuated and no longer significant after
      multivariable adjustment for classical CVD risk factors. Strikingly, ferritin
      concentrations were positively associated with a majority of classical CVD risk
      factors (age, male sex, alcohol intake, obesity, inflammation, and lower
      education). Conclusion: Increased ferritin concentrations may be a marker of an
      overall unfavorable risk factor profile rather than a mediator of greater CVD
      risk due to meat consumption.

PMID- 29381788
TI  - Sleep extension is a feasible lifestyle intervention in free-living adults who
      are habitually short sleepers: a potential strategy for decreasing intake of free
      sugars? A randomized controlled pilot study.
AB  - Background: Evidence suggests that short sleep duration may be a newly identified
      modifiable risk factor for obesity, yet there is a paucity of studies to
      investigate this. Objective: We assessed the feasibility of a personalized sleep
      extension protocol in adults aged 18-64 y who are habitually short sleepers (5 to
      <7 h), with sleep primarily measured by wrist actigraphy. In addition, we
      collected pilot data to assess the effects of extended sleep on dietary intake
      and quality measured by 7-d food diaries, resting and total energy expenditure,
      physical activity, and markers of cardiometabolic health. Design: Forty-two
      normal-weight healthy participants who were habitually short sleepers completed
      this free-living, 4-wk, parallel-design randomized controlled trial. The sleep
      extension group (n = 21) received a behavioral consultation session targeting
      sleep hygiene. The control group (n = 21) maintained habitual short sleep.
      Results: Rates of participation, attrition, and compliance were 100%, 6.5%, and
      85.7%, respectively. The sleep extension group significantly increased time in
      bed [0:55 hours:minutes (h:mm); 95% CI: 0:37, 1:12 h:mm], sleep period (0:47
      h:mm; 95% CI: 0:29, 1:05 h:mm), and sleep duration (0:21 h:mm; 95% CI: 0:06, 0:36
      h:mm) compared with the control group. Sleep extension led to reduced intake of
      free sugars (-9.6 g; 95% CI: -16.0, -3.1 g) compared with control (0.7 g; 95% CI:
      -5.7, 7.2 g) (P = 0.042). A sensitivity analysis in plausible reporters showed
      that the sleep extension group reduced intakes of fat (percentage), carbohydrates
      (grams), and free sugars (grams) in comparison to the control group. There were
      no significant differences between groups in markers of energy balance or
      cardiometabolic health. Conclusions: We showed the feasibility of extending sleep
      in adult short sleepers. Sleep extension led to reduced free sugar intakes and
      may be a viable strategy to facilitate limiting excessive consumption of free
      sugars in an obesity-promoting environment. This trial was registered at
      www.clinicaltrials.gov as NCT02787577.

PMID- 29381789
TI  - Comparison of self-reported dietary intakes from the Automated Self-Administered
      24-h recall, 4-d food records, and food-frequency questionnaires against recovery
      biomarkers.
AB  - Background: A limited number of studies have evaluated self-reported dietary
      intakes against objective recovery biomarkers. Objective: The aim was to compare
      dietary intakes of multiple Automated Self-Administered 24-h recalls (ASA24s), 4
      d food records (4DFRs), and food-frequency questionnaires (FFQs) against recovery
      biomarkers and to estimate the prevalence of under- and overreporting. Design:
      Over 12 mo, 530 men and 545 women, aged 50-74 y, were asked to complete 6 ASA24s
      (2011 version), 2 unweighed 4DFRs, 2 FFQs, two 24-h urine collections (biomarkers
      for protein, potassium, and sodium intakes), and 1 administration of doubly
      labeled water (biomarker for energy intake). Absolute and density-based energy
      adjusted nutrient intakes were calculated. The prevalence of under- and
      overreporting of self-report against biomarkers was estimated. Results: Ninety
      two percent of men and 87% of women completed >=3 ASA24s (mean ASA24s completed:
      5.4 and 5.1 for men and women, respectively). Absolute intakes of energy,
      protein, potassium, and sodium assessed by all self-reported instruments were
      systematically lower than those from recovery biomarkers, with underreporting
      greater for energy than for other nutrients. On average, compared with the energy
      biomarker, intake was underestimated by 15-17% on ASA24s, 18-21% on 4DFRs, and 29
      34% on FFQs. Underreporting was more prevalent on FFQs than on ASA24s and 4DFRs
      and among obese individuals. Mean protein and sodium densities on ASA24s, 4DFRs,
      and FFQs were similar to biomarker values, but potassium density on FFQs was 26
      40% higher, leading to a substantial increase in the prevalence of overreporting
      compared with absolute potassium intake. Conclusions: Although misreporting is
      present in all self-report dietary assessment tools, multiple ASA24s and a 4DFR
      provided the best estimates of absolute dietary intakes for these few nutrients
      and outperformed FFQs. Energy adjustment improved estimates from FFQs for protein
      and sodium but not for potassium. The ASA24, which now can be used to collect
      both recalls and records, is a feasible means to collect dietary data for
      nutrition research.

PMID- 29381791
TI  - Evaluation of meal replacements and a home food environment intervention for long
      term weight loss: a randomized controlled trial.
AB  - Background: Lifestyle change treatments for weight loss produce medically
      meaningful weight reductions, but lost weight is usually regained. Meal
      replacements (MRs) represent one avenue for improving long-term weight loss.
      Another, nutrition-focused approach involves having participants make specific
      changes in the energy density, composition, and structure of the foods in their
      personal food environments. Objective: Three conditions were compared: behavior
      therapy (BT), BT plus MRs (BT+MR), and a nutrition-focused treatment aimed at
      modifying the home food environment (HFE). Design: Overweight and obese
      individuals (n = 262) were randomly assigned to 1 of the 3 conditions. Treatment
      occurred in weekly groups for 6 mo and in biweekly groups for 6 mo. Assessments
      were conducted at baseline and at 6, 12, 18, 24, and 36 mo. Multilevel models
      were used to estimate weight-change trajectories for each participant and to
      examine the treatment group effect on long-term weight loss. Results: A
      multilevel analysis indicated that all 3 groups showed significant weight loss
      over 12 mo that was gradually regained to the 36-mo follow-up. Mean +/- SD
      percentages of baseline weight loss at 12 mo for BT, BT+MR, and HFE were 9.41% +/
      7.92%, 10.37% +/- 7.77%, and 10.97% +/- 7.79%, respectively. Comparable
      percentages at 36 mo were 4.21% +/- 8.64%, 3.06% +/- 6.93%, and 4.49% +/- 7.83%.
      Those in the HFE condition lost more weight than those receiving BT through the
      36-mo assessment (P < 0.01), as reflected in 2 treatment * time interactions.
      Further analyses showed that HFE produced the largest increases in cognitive
      restraint and that this increase largely mediated the HFE group's improved weight
      loss. Conclusion: The nutrition-focused intervention studied here produced
      modestly greater long-term weight loss than BT, an effect that was largely
      explainable by an unexpected boost in cognitive restraint in this condition. This
      study was registered at clinicaltrials.gov as NCT01065974.

PMID- 29381790
TI  - Adherence to a healthy eating index for pregnant women is associated with lower
      neonatal adiposity in a multiethnic Asian cohort: the Growing Up in Singapore
      Towards healthy Outcomes (GUSTO) Study.
AB  - Background: Evidence linking maternal diet quality during pregnancy with infant
      birth outcomes is limited in Asia. Objective: We investigated the association of
      maternal diet quality with the risk of preterm birth, offspring birth size, and
      adiposity in a multiethnic Asian birth cohort. Design: Dietary intakes of 1051
      pregnant women were ascertained at 26-28 wk of gestation with the use of 24-h
      recalls and 3-d food diaries, from which diet quality (score range: 0-100) was
      measured by the Healthy Eating Index for pregnant women in Singapore (HEI-SGP).
      Gestational age was established by first-trimester ultrasound dating scan.
      Neonatal weight and length were measured at birth. Body composition was assessed
      by air displacement plethysmography in a subset of infants (n = 313) within 72 h
      after birth, and abdominal adiposity was assessed by MRI (n = 316) within the
      first 2 wk of life. Associations were assessed by multivariable linear regression
      for continuous outcomes and logistic regression for preterm birth. Results: The
      mean +/- SD maternal HEI-SGP score was 52.1 +/- 13.6. Maternal diet quality
      during pregnancy was not associated with preterm birth or birth weight. Greater
      adherence to the HEI-SGP (per 10-point increment in HEI-SGP score) was associated
      with longer birth length [beta (95% CI): 0.14 (0.03, 0.24 cm)], lower body mass
      index (in kg/m2) at birth [-0.07 (-0.13, -0.01)], lower sum of triceps and
      subscapular skinfold thickness [-0.15 (-0.26, -0.05 mm)], lower percentage body
      fat [-0.52% (-0.84%, -0.20%)], lower fat mass [-17.23 (-29.52, -4.94 g)], lower
      percentage abdominal superficial subcutaneous adipose tissue [-0.16% (-0.30%, 
      0.01%)], and lower percentage deep subcutaneous adipose tissue [-0.06% (-0.10%, 
      0.01%)]. Conclusions: Higher maternal diet quality during pregnancy was
      associated with longer birth length and lower neonatal adiposity but not with
      birth weight and preterm birth. These findings warrant further investigation in
      independent studies. This trial was registered at clinicaltrials.gov as
      NCT01174875.

PMID- 29381792
TI  - Overweight in childhood cancer survivors: the Swiss Childhood Cancer Survivor
      Study.
AB  - Background: An increased risk of becoming overweight has been reported for
      childhood cancer survivors (CCSs), in particular leukemia survivors, although the
      evidence is inconclusive. Objective: We assessed the prevalence of overweight in
      CCSs, with a focus on leukemia survivors, compared it with their peers, and
      determined potential risk factors. Design: As part of the Swiss Childhood Cancer
      Survivor Study, we sent a questionnaire between 2007 and 2013 to all Swiss
      resident CCSs aged <21 y at diagnosis who had survived >=5 y. We calculated body
      mass index (BMI) from medical records at diagnosis and self-reported heights and
      weights at survey. We calculated BMI z scores by using Swiss references for
      children and compared overweight prevalence in CCSs, their siblings, and the
      general population with the use of the Swiss Health Survey (SHS) and assessed
      risk factors for being overweight by using multivariable logistic regression.
      Results: The study included 2365 CCSs, 819 siblings, and 9591 SHS participants.
      At survey, at an average of 15 y after diagnosis, the prevalence of overweight in
      CCSs overall (26%) and in leukemia survivors (26%) was similar to that in
      siblings (22%) and the general population (25%). Risk factors for being
      overweight in CCSs were male sex (OR: 1.8; 95% CI: 1.5, 2.1), both young (OR for
      ages 5-14 y: 1.6; 95% CI: 1.2, 2.3) and older (range-OR for ages 25-29 y: 1.7;
      95% CI: 1.2, 2.4; OR for ages 40-45 y: 4.0; 95% CI: 2.5, 6.5) age at study, lower
      education (OR: 1.4; 95% CI: 1.1, 1.8), migration background (OR: 1.3; 95% CI:
      1.1, 1.7), and no sports participation (OR: 1.4; 95% CI: 1.1, 1.7). Risk factors
      for overweight were similar in peers. CCSs treated with cranial radiotherapy
      (>=20 Gy) were more likely to be overweight than their peers (OR: 1.6; 95% CI:
      1.2, 2.2). Conclusions: The prevalence of and risk factors for being overweight
      are similar in long-term CCSs and their peers. This suggests that prevention
      methods can be the same as in the general population. An important exception is
      CCSs treated with cranial radiotherapy >=20 Gy who may need extra attention
      during follow-up care. This study was registered at clinicaltrials.gov as
      NCT03297034.

PMID- 29381793
TI  - Intrauterine DHA exposure and child body composition at 5 y: exploratory analysis
      of a randomized controlled trial of prenatal DHA supplementation.
AB  - Background: Observational studies find associations between maternal
      docosahexaenoic acid (DHA) and greater fat-free mass and lower percentage of body
      fat, but randomized trials of prenatal DHA supplementation have not found
      significant intent-to-treat effects on childhood body composition. Objective:
      This study sought to explore associations between intrauterine DHA exposure and
      body composition and size at 5 y in the offspring of women who participated in a
      randomized trial of prenatal DHA supplementation (corn and soybean oil placebo or
      600 mg/d). Design: At 5 y, body composition was measured by air displacement
      plethysmography in 154 offspring of women who had participated in the Kansas
      University DHA Outcomes Study and who had red blood cell (RBC) phospholipid (PL)
      fatty acids assessed at enrollment and delivery. We used linear regression models
      to analyze the relation among 3 indicators of intrauterine DHA exposure-1) intent
      to-treat (placebo or DHA), 2) maternal RBC PL DHA status at delivery, and 3)
      change in maternal DHA (delivery minus enrollment)-and 6 outcomes of interest: 5
      y fat mass, fat-free mass, percentage of body fat, height, weight, and body mass
      index z score. Results: Change in maternal RBC PL DHA correlated with higher fat
      free mass (r = 0.21, P = 0.0088); the association was unchanged after adjustment
      for maternal, perinatal, and childhood dietary factors. Intent-to-treat and DHA
      status at delivery showed positive trends with fat-free mass that were not
      statistically significant. There was no evidence relating intrauterine DHA
      exposure to any other body composition measure. Conclusions: Change in maternal
      DHA status during pregnancy was related to higher offspring 5-y fat-free mass.
      The other 2 indicators of intrauterine exposure to DHA suggested a trend for
      higher offspring 5-y fat-free mass. Our findings agree with an earlier
      observational study from the United Kingdom. This trial was registered at
      clinicaltrials.gov as NCT00266825.

PMID- 29381794
TI  - Intake of free sugars and micronutrient dilution in Australian adults.
AB  - Background: The negative health effect of excessive intake of free sugars has
      been gaining increasing public awareness. Objective: This secondary analysis
      aimed to evaluate the impact of free-sugar intake on micronutrient dilution, and
      estimate a threshold level of free-sugar intake at which a decrease in
      micronutrient intake becomes evident, based on data from the Australian Health
      Survey 2011-2012. Design: Dietary data from adult respondents (weighted n = 6150)
      who had completed two 24-h recalls were analyzed. A published 10-step methodology
      was adopted and used to estimate the free-sugar intake of the respondents. Six
      modified cut-offs for percentage of energy of free sugars (%EFS) were created
      based on recommendations from the WHO and the Institute of Medicine to examine
      the association between %EFS on micronutrient intakes. Estimated marginal means
      and SEs were calculated using ANCOVA. Logistic regression was used to calculate
      the ORs of not meeting the nutrient reference values for Australia and New
      Zealand for each micronutrient with an increase in free-sugar intake. Analyses
      were adjusted for age, sex, socioeconomic status, country of birth, whether
      dieting, smoking status, and remoteness of living area. Results: Peak intake for
      most micronutrients was observed at %EFS between 5% and <15%. A significant
      reduction in most micronutrient intakes was observed at >25%EFS. At <5%EFS, some
      micronutrient intakes were reduced. Only small variations in micronutrient
      consumptions were observed when %EFS was between 5% and 25%. Core food intake
      decreased and discretionary food increased with an increase in free-sugar intake.
      Conclusion: A high free-sugar intake, particularly >25%EFS, was found to have a
      significant diluting effect on most nutrients. However, a free-sugar intake
      <5%EFS may increase the risk of undesirably low micronutrient consumption related
      to inadequate total energy intake. This secondary analysis was registered at
      anzctr.org.au as ACTRN12617000917336.

PMID- 29381795
TI  - The PAr index, an indicator reflecting altered vitamin B-6 homeostasis, is
      associated with long-term risk of stroke in the general population: the Hordaland
      Health Study (HUSK).
AB  - Background: Vitamin B-6 homeostasis is altered during inflammation and immune
      activation. It is unknown whether altered vitamin B-6 homeostasis is associated
      with the risk of stroke. Objective: We investigated the relation between the
      ratio plasma 4-pyridoxic acid: (pyridoxal + pyridoxal-5'-phosphate) (PAr) as an
      indicator of altered vitamin B-6 homeostasis and the risk of stroke in the
      general population. Design: We conducted a prospective analysis of the community
      based Hordaland Health Study (HUSK) in 6891 adults (born during 1925-1927 and
      1950-1951) without known stroke at baseline (1998-1999). Participants were
      followed via linkage to the CVDNOR (Cardiovascular Disease in Norway) project and
      the Cause of Death Registry. HRs and 95% CIs were calculated using Cox
      proportional hazards analyses. Results: A total of 390 participants (193 men and
      197 women) developed stroke over a median follow-up period of 11 y. Study
      participants with elevated PAr experienced a higher risk of incident stroke in an
      essentially linear dose-response fashion. The HR (95% CI) for the highest
      compared with the lowest quartile of PAr was 1.97 (1.42, 2.73; P-trend <0.001)
      for total stroke and 2.09 (1.42, 3.09; P-trend <0.001) for ischemic stroke after
      adjustment for age, sex, body mass index (BMI), smoking, education, physical
      activity, estimated glomerular filtration rate, hypertension, diabetes, total
      cholesterol, and statin use. PAr had greater predictive strength than did C
      reactive protein, current smoking, diabetes, hypertension, estimated glomerular
      filtration rate, and physical activity. The associations were similar in
      subgroups stratified by age group, sex, BMI, current smoking, hypertension,
      diabetes, and statin use at baseline. Conclusions: Higher plasma PAr was
      independently associated with increased risk of incident stroke in all
      participants and across all subgroups stratified by conventional risk predictors.
      Our novel findings point to and expand the range of inflammation and immune
      activation processes that may be relevant for the pathogenesis and prevention of
      stroke. This trial was registered at clinicaltrials.gov as NCT03013725.

PMID- 29381797
TI  - International food group-based diet quality and risk of coronary heart disease in
      men and women.
AB  - Background: Standard diet quality assessment tools, which measure micronutrient
      sufficiency and food consumption related to disease and applicable to different
      populations, are needed to track progress in meeting the Sustainable Development
      Goals related to hunger, food security, and nutrition. Diet quality scores have
      been constructed for high- and low-income countries, but none are simple to
      administer or applicable internationally. Objective: We prospectively examined
      the association between the Food Group Index (FGI), the Minimal Diet Diversity
      Score for Women (MDDW), and a new Prime Diet Quality Score (PDQS), and the risk
      of ischemic heart disease (IHD) in 3 US cohorts. Design: In total, 75,045 women
      (baseline age 43-63 y), 43,966 men (aged 40-75 y), and 93,131 younger women (aged
      27-44 y) without a history of cardiovascular disease were followed up to 28 y.
      Diet was assessed multiple times using food frequency questionnaires and the 3
      diet quality scores were computed for each individual. The association with IHD
      was modeled with Cox proportional hazard models, controlling for potential
      confounders. Results: During follow-up, we ascertained 2908 incident IHD cases in
      the Nurses' Health Study, 3722 in the Health Professionals Follow-up Study, and
      505 in the Nurses' Health Study II. The FGI was not associated with total IHD in
      any cohort. The PDQS was significantly associated with IHD in all 3 cohorts
      separately and the pooled RR for each SD increase was 0.89 (95% CI: 0.87, 0.91).
      This was significantly different than the pooled RR of 0.93 for MDDW (95% CI:
      0.90, 0.96) and the RR of 0.98 for the FGI (95% CI: 0.95, 1.01). The association
      did not appear to differ by age. Conclusion: We found that the PDQS with the most
      detailed differentiation of healthy and unhealthy foods was associated with a
      lower risk of IHD in a high-income country. On the other hand, diet quality
      scores that do not account for unhealthy foods had a limited association with
      IHD.

PMID- 29381796
TI  - Substitution of dietary omega-6 polyunsaturated fatty acids for saturated fatty
      acids decreases LDL apolipoprotein B-100 production rate in men with dyslipidemia
      associated with insulin resistance: a randomized controlled trial.
AB  - Background: The substitution of omega (omega)-6 (n-6) polyunsaturated fatty acids
      (PUFAs) for saturated fatty acids (SFAs) is advocated in cardiovascular disease
      prevention. The impact of this substitution on lipoprotein metabolism in subjects
      with dyslipidemia associated with insulin resistance (IR) remains unknown.
      Objective: In men with dyslipidemia and IR, we evaluated the impact of
      substituting omega-6 PUFAs for SFAs on the in vivo kinetics of apolipoprotein
      (apo) B-containing lipoproteins and on the intestinal expression of key genes
      involved in lipoprotein metabolism. Design: Dyslipidemic and IR men (n = 36) were
      recruited for this double-blind, randomized, crossover, controlled trial.
      Subjects consumed, in a random order, a fully controlled diet rich in SFAs (SFAs:
      13.4% of energy; omega-6 PUFAs: 4.0%) and a fully controlled diet rich in omega-6
      PUFAs (SFAs: 6.0%; omega-6 PUFAs: 11.3%) for periods of 4 wk, separated by a 4-wk
      washout period. At the end of each diet, the in vivo kinetics of apoB-containing
      lipoproteins were measured and the intestinal expression of key genes involved in
      lipoprotein metabolism was quantified in duodenal biopsies taken from each
      participant. Results: The substitution of omega-6 PUFAs for SFAs had no impact on
      TRL apoB-48 fractional catabolic rate (Delta = -3.8%, P = 0.7) and production
      rate (Delta = +1.2%, P = 0.9), although it downregulated the intestinal
      expression of the microsomal triglyceride transfer protein (Delta = -18.4%, P =
      0.006) and apoB (Delta = -16.6%, P = 0.005). The substitution of omega-6 PUFAs
      for SFAs decreased the LDL apoB-100 pool size (Delta = -7.8%; P = 0.005). This
      difference was attributed to a reduction in the LDL apoB-100 production rate
      after the substitution of omega-6 PUFAs for SFAs (Delta = -10.0%; P = 0.003).
      Conclusions: This study demonstrates that the substitution of dietary omega-6
      PUFAs for SFAs decreases the production and number of LDL particles in men with
      dyslipidemia and IR. This trial was registered at clinicaltrials.gov as
      NCT01934543.

PMID- 29381798
TI  - The effects of Ramadan fasting on activity and energy expenditure.
AB  - Background: Fasting during the month of Ramadan entails abstinence from eating
      and drinking between dawn and sunset and a major shift in meal times and patterns
      with associated changes in several hormones and circadian rhythms; whether there
      are accompanying changes in energy metabolism is unclear. Objective: We have
      investigated the impact of Ramadan fasting on resting metabolic rate (RMR),
      activity, and total energy expenditure (TEE). Design: Healthy nonobese volunteers
      (n = 29; 16 women) fasting during Ramadan were recruited. RMR was measured with
      the use of indirect calorimetry. In subgroups of participants, activity (n = 11;
      5 women) and TEE (n = 10; 5 women) in free-living conditions were measured with
      the use of accelerometers and the doubly labeled water technique, respectively.
      Body composition was measured with the use of bioelectrical impedance.
      Measurements were repeated after a wash-out period of between 1 and 2 mo after
      Ramadan. Nonparametric tests were used for comparative statistics. Results:
      Ramadan fasting did not result in any change in RMR (mean +/- SD: 1365.7 +/-
      230.2 compared with 1362.9 +/- 273.6 kcal/d for Ramadan and post-Ramadan
      respectively, P = 0.713, n = 29). However, controlling for the effects of age,
      sex, and body weight, RMR was higher in the first week of Ramadan than in
      subsequent weeks. During Ramadan, the total number of steps walked were
      significantly lower (n = 11, P = 0.001), while overall sleeping time was reduced
      and different sleeping patterns were seen. TEE did not differ significantly
      between Ramadan and post-Ramadan (mean +/- SD: 2224.1 +/- 433.7 compared with
      2121.0 +/- 718.5 kcal/d for Ramadan and post-Ramadan, P = 0.7695, n = 10).
      Conclusions: Ramadan fasting is associated with reduced activity and sleeping
      time, but no significant change in RMR or TEE. Reported weight changes with
      Ramadan in other studies are more likely to be due to differences in food intake.
      This trial is registered at clinicaltrials.gov as NCT02696421.

PMID- 29381799
TI  - Long-term supplementation with folic acid and vitamin B-12 has no effect on
      circulating uric acid concentrations in Norwegian patients with coronary artery
      disease.

PMID- 29381801
TI  - With Appreciation 2017.

PMID- 29381800
TI  - Reply to J Dierkes et al.

PMID- 29381802
TI  - The effect of consumption temperature on the homeostatic and hedonic responses to
      glucose ingestion in the hypothalamus and the reward system.
AB  - Background: Excessive consumption of sugar-sweetened beverages (SSBs) has been
      associated with obesity and related diseases. SSBs are often consumed cold, and
      both the energy content and temperature might influence the consumption behavior
      for SSBs. Objective: The main aim of this study was to elucidate whether
      consumption temperature and energy (i.e., glucose) content modulate homeostatic
      (hypothalamus) and reward [ventral tegmental area (VTA)] responses. Design:
      Sixteen healthy men participated in our study [aged 18-25 y; body mass index
      (kg/m2): 20-23]. High-resolution functional magnetic resonance imaging data were
      collected after ingestion of 4 different study stimuli: plain tap water at room
      temperature (22 degrees C), plain tap water at 0 degrees C, a glucose-containing
      beverage (75 g glucose dissolved in 300 mL water) at 22 degrees C, and a similar
      glucose drink at 0 degrees C. Blood oxygen level-dependent (BOLD) changes from
      baseline (7 min preingestion) were analyzed over time in the hypothalamus and VTA
      for individual stimulus effects and for effects between stimuli. Results: In the
      hypothalamus, water at 22 degrees C led to a significantly increased BOLD
      response; all other stimuli resulted in a direct, significant decrease in BOLD
      response compared with baseline. In the VTA, a significantly decreased BOLD
      response compared with baseline was found after the ingestion of stimuli
      containing glucose at 0 degrees C and 22 degrees C. These responses were not
      significantly modulated by consumption temperature. The consumption of plain
      water did not have a significant VTA BOLD effect. Conclusions: Our data show that
      glucose at 22 degrees C, glucose at 0 degrees C, and water at 0 degrees C lowered
      hypothalamic activity, which is associated with increased satiation. On the
      contrary, the consumption of water at room temperature increased activity. All
      stimuli led to a similar VTA response, which suggests that all drinks elicited a
      similar hedonic response. Our results indicate that, in addition to glucose, the
      low temperature at which SSBs are often consumed also leads to a response from
      the hypothalamus and might strengthen the response of the VTA. This trial was
      registered at www.clinicaltrials.gov as NCT03181217.

PMID- 29381803
TI  - Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure
      associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT
      positive humans confirmed by positron emission tomography scan.
AB  - Background: Capsinoids are reported to increase energy expenditure (EE) via brown
      adipose tissue (BAT) stimulation. However, imaging of BAT activation by
      capsinoids remains limited. Because BAT activation is a potential therapeutic
      strategy for obesity and related metabolic disorders, we sought to prove that
      capsinoid-induced BAT activation can be visualized by 18-fluorine
      fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Objective: We
      compared capsinoids and cold exposure on BAT activation and whole-body EE.
      Design: Twenty healthy participants (8 men, 12 women) with a mean age of 26 y
      (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0)
      underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg
      capsinoids or <=2 h of cold exposure (~14.5 degrees C) in a crossover design.
      Mean standardized uptake values (SUVs) of the region of interest and BAT volumes
      were calculated. Blood metabolites were measured before and 2 h after each
      treatment. Results: All of the participants showed negligible 18F-FDG uptake post
      capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG
      uptake into supraclavicular and lateral neck adipose tissues (BAT-positive
      group), whereas the remaining 8 participants (BAT-negative group) showed
      undetectable uptake. Capsinoids and cold exposure increased EE, although cold
      induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin
      sensitivity, and HDL cholesterol compared with capsinoids. Conclusions:
      Capsinoids only increased EE in BAT-positive participants, which suggests that
      BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT
      to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the
      presently accepted SUV thresholds defining BAT activation. This trial was
      registered at www.clinicaltrials.gov as NCT02964442.

PMID- 29381804
TI  - Dietary assessment in the digital age: the ongoing quest for better methods.

PMID- 29381805
TI  - A loop-mediated isothermal amplification procedure targeting the sodA gene for
      rapid and specific identification of Gallibacterium anatis.
AB  - This paper reports on the development and validation of a real-time loop-mediated
      isothermal amplification assay (LAMP) for rapid and specific identification of
      Gallibacterium anatis. To design a set of 6 primers using the LAMP technique, the
      conserved region of the G. anatis sodA gene was selected as a target. To evaluate
      primer specificity we used 120 field strains, the reference strain G. anatis ATCC
      43329, and 9 non-G. anatis bacteria. The results confirmed positive reactions for
      all G. anatis strains tested by LAMP at 63 degrees C for 60 min, with no cross
      reactivity observed for the negative control bacteria, i.e., Haemophilus
      parainfluenzae (ATCC 51505 and ATCC 33392), Aggregatibacter aphrophilus ATCC
      7901, Avibacterium endocarditis, Pasteurella multocida, Actinobacillus
      pleuropneumoniae, Avibacterium paragallinarum, Ornithobacterium rhinotracheale,
      and Escherichia coli. The lowest detectable amount of DNA for the LAMP reaction
      was 0.2561 pg, which was detected in about 34 min, while the highest available
      concentration of the G. anatis reference strain was detected in about 10 min. The
      lowest detectable amount of DNA for the real-time PCR reaction was 21.24 pg,
      which was detected in about 20 min, while the highest available concentration of
      the G. anatis reference strain was detected in about 7 min. Moreover, using the
      real-time LAMP assay the reaction could be effectively carried out in a volume of
      just 13 MUL, about half the officially recommended reaction volume (25 MUL). The
      aim of this study was to develop a highly sensitive and specific G. anatis real
      time LAMP assay that is less time-consuming and less costly than quantitative
      PCR.

PMID- 29381806
TI  - Targeting Pin1 by inhibitor API-1 regulates microRNA biogenesis and suppresses
      hepatocellular carcinoma development.
AB  - : Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide,
      but there are few effective treatments. Aberrant microRNA (miRNA) biogenesis is
      correlated with HCC development. We previously demonstrated that peptidyl-prolyl
      cis-trans isomerase NIMA-interacting 1 (Pin1) participates in miRNA biogenesis
      and is a potential HCC treatment target. However, how Pin1 modulates miRNA
      biogenesis remains obscure. Here, we present in vivo evidence that Pin1
      overexpression is directly linked to the development of HCC. Administration with
      the Pin1 inhibitor (API-1), a specific small molecule targeting Pin1 peptidyl
      prolyl isomerase domain and inhibiting Pin1 cis-trans isomerizing activity,
      suppresses in vitro cell proliferation and migration of HCC cells. But API-1
      induced Pin1 inhibition is insensitive to HCC cells with low Pin1 expression
      and/or low exportin-5 (XPO5) phosphorylation. Mechanistically, Pin1 recognizes
      and isomerizes the phosphorylated serine-proline motif of phosphorylated XPO5 and
      passivates phosphorylated XPO5. Pin1 inhibition by API-1 maintains the active
      conformation of phosphorylated XPO5 and restores XPO5-driven precursor miRNA
      nuclear-to-cytoplasm export, activating anticancer miRNA biogenesis and leading
      to both in vitro HCC suppression and HCC suppression in xenograft mice.
      CONCLUSION: Experimental evidence suggests that Pin1 inhibition by API-1 up
      regulates miRNA biogenesis by retaining active XPO5 conformation and suppresses
      HCC development, revealing the mechanism of Pin1-mediated miRNA biogenesis and
      unequivocally supporting API-1 as a drug candidate for HCC therapy, especially
      for Pin1-overexpressing, extracellular signal-regulated kinase-activated HCC.
      (Hepatology 2018).

PMID- 29381807
TI  - Facioscapulohumeral muscular dystrophy functional composite outcome measure.
AB  - INTRODUCTION: We developed an evaluator-administered functional
      facioscapulohumeral muscular dystrophy composite outcome measure (FSHD-COM)
      comprising patient-identified areas of functional burden for future clinical
      trials. METHODS: We performed a prospective observational study of 41 patients
      with FSHD at 2 sites. The FSHD-COM includes functional assessment of the legs,
      shoulders and arms, trunk, hands, and balance/mobility. We determined the test
      retest reliability and convergent validity compared to established FSHD disease
      metrics. RESULTS: The FSHD-COM demonstrated excellent test-retest reliability
      (intraclass correlation coefficient [ICC] 0.96; subscale ICC range, 0.90-0.94).
      Cross-sectional associations between the FSHD-COM and disease duration, clinical
      severity, and strength were moderate to strong (Pearson correlation coefficient
      range |0.51-0.92|). DISCUSSION: The FSHD-COM is a disease-relevant, functional
      composite outcome measure suitable for future FSHD clinical trials that shows
      excellent test-retest reliability and cross-sectional associations to disease
      measures. Future directions include determining multisite reliability,
      sensitivity to change, and the minimal clinically important change in the FSHD
      COM. Muscle Nerve, 2018.

PMID- 29381810
TI  - Mcleod syndrome is a new cause of axial muscle weakness.

PMID- 29381808
TI  - Pre-drill Groundwater Geochemistry in the Karoo Basin, South Africa.
AB  - Enhanced production of unconventional hydrocarbons in the United States has
      driven interest in natural gas development globally, but simultaneously raised
      concerns regarding water quantity and quality impacts associated with hydrocarbon
      extraction. We conducted a pre-development assessment of groundwater geochemistry
      in the critically water-restricted Karoo Basin, South Africa. Twenty-two springs
      and groundwater samples were analyzed for major dissolved ions, trace elements,
      water stable isotopes, strontium and boron isotopes, hydrocarbons and helium
      composition. The data revealed three end-members: a deep, saline groundwater with
      a sodium-chloride composition, an old, deep freshwater with a sodium-bicarbonate
      chloride composition and a shallow, calcium-bicarbonate freshwater. In a few
      cases, we identified direct mixing of the deep saline water and shallow
      groundwater. Stable water isotopes indicate that the shallow groundwater was
      controlled by evaporation in arid conditions, while the saline waters were
      diluted by apparently fossil meteoric water originated under wetter climatic
      conditions. These geochemical and isotopic data, in combination with elevated
      helium levels, suggest that exogenous fluids are the source of the saline
      groundwater and originated from remnant seawater prior to dilution by old
      meteoric water combined with further modification by water-rock interactions.
      Samples with elevated methane concentrations (>14 ccSTP/kg) were strongly
      associated with the sodium-chloride water located near dolerite intrusions, which
      likely provide a preferential pathway for vertical migration of deeply sourced
      hydrocarbon-rich saline waters to the surface. This pre-drill evaluation
      indicates that the natural migration of methane- and salt-rich waters provides a
      source of geogenic contamination to shallow aquifers prior to shale gas
      development in the Karoo Basin.

PMID- 29381811
TI  - Less can be more: A finite treatment approach for HBeAg-negative chronic
      hepatitis B.

PMID- 29381809
TI  - Tumor progression locus 2 in hepatocytes potentiates both liver and systemic
      metabolic disorders in mice.
AB  - : Tumor progression locus 2 (TPL2), a serine/threonine kinase, has been regarded
      as a potentially interesting target for the treatment of various diseases with an
      inflammatory component. However, the function of TPL2 in regulating hepatocyte
      metabolism and liver inflammation during the progression of nonalcoholic fatty
      liver disease (NAFLD) is poorly understood. Here, we report that TPL2 protein
      expression was significantly increased in fatty liver from diverse species,
      including humans, monkeys, and mice. Further investigations revealed that
      compared to wild-type (WT) littermates, hepatocyte-specific TPL2 knockout (HKO)
      mice exhibited improved lipid and glucose imbalance, reserved insulin
      sensitivity, and alleviated inflammation in response to high-fat diet (HFD)
      feeding. Overexpression of TPL2 in hepatocytes led to the opposite phenotype.
      Regarding the mechanism, we found that mitogen-activated protein kinase kinase 7
      (MKK7) was the specific substrate of TPL2 for c-Jun N-terminal kinase (JNK)
      activation. TPL2-MKK7-JNK signaling in hepatocytes represents a promising
      drugable target for treating NAFLD and associated metabolic disorders.
      CONCLUSION: In hepatocytes, TPL2 acts as a key mediator that promotes both liver
      and systemic metabolic disturbances by specifically increasing MKK7-JNK
      activation. (Hepatology 2018).

PMID- 29381812
TI  - Motor unit number index and neurophysiological index as candidate biomarkers of
      presymptomatic motor neuron loss in amyotrophic lateral sclerosis.
AB  - INTRODUCTION: Our objective was to determine the utility of motor unit number
      index (MUNIX) and neurophysiological index (NI) as surrogate biomarkers of
      disease progression in limbs without clinical signs of lower motor neuron (LMN)
      involvement from patients with slowly progressive amyotrophic lateral sclerosis
      (ALS). METHODS: Patients with slowly progressive ALS and at least 1 clinically
      unaffected limb were prospectively enrolled. Clinical signs of LMN loss and
      results from hand-held dynamometer (HHD), revised ALS Functional Rating Scale
      (ALSFRS-R), mean-MUNIX (from 3 different muscles), and NI were longitudinally
      recorded. RESULTS: Eighteen patients with 43 presymptomatic muscles were
      evaluated. Twenty-seven muscles remained clinically unaffected during study, with
      stable ALSFRS-R subscores and HHD measures. However, a significant decline in
      mean-MUNIX and NI was detected. DISCUSSION: Mean-MUNIX and NI were more sensitive
      than clinical measures at detecting LMN loss in presymptomatic limbs from
      patients with slowly progressive ALS. Therefore, these electrophysiological
      biomarkers should be included in early study phases as meaningful outcome
      measures. Muscle Nerve 58: 204-212, 2018.

PMID- 29381813
TI  - Clinical neuropsychology in the management of myotonic dystrophy.

PMID- 29381814
TI  - Quality measures: Do they measure up?

PMID- 29381815
TI  - Effects of polyphenols on doxorubicin-induced oral keratinocyte cytotoxicity and
      anticancer potency against oral cancer cells.
AB  - BACKGROUND: Normal human oral keratinocytes are highly sensitive to anticancer
      drugs including doxorubicin. Resveratrol, epigallocatechin gallate, and tannic
      acid are polyphenolic compounds that were reported to have cardioprotective
      effect when combined with doxorubicin. However, it is unknown whether these
      polyphenols could protect normal human oral keratinocytes against doxorubicin
      induced cytotoxicity without weakening its cytotoxic potential against oral
      cancer cells. Here, we examined the effects of the 3 polyphenolic compounds on
      doxorubicin-induced cytotoxicity in normal human oral keratinocytes and also
      investigated their effects on doxorubicin potency in HSC-2 human oral squamous
      cell carcinoma cells. METHODS: Cell viability was evaluated, followed by the
      analysis of apoptosis and necrosis. The changes in intracellular reactive oxygen
      species at the early stage after treatment were also examined. RESULTS: The
      results revealed that resveratrol in combination with doxorubicin additively
      augmented doxorubicin cytotoxicity in both types of cells. However,
      epigallocatechin gallate and tannic acid at a certain concentration mitigated the
      doxorubicin-induced keratinocyte toxicity mainly due to reduced doxorubicin
      induced necrosis in normal human oral keratinocytes without weaken doxorubicin
      anticancer efficacy. The exact mechanism is still unknown but intracellular
      reactive oxygen species might be not the sole factor. CONCLUSIONS: This study for
      the first time reported the effects of resveratrol, epigallocatechin gallate, and
      tannic acid on doxorubicin-induced cytotoxicity in normal oral keratinocytes and
      oral cancer cells. The combined use of epigallocatechin gallate or tannic acid
      with doxorubicin at a certain concentration could mitigate doxorubicin-induced
      keratinocyte cytotoxicity without weakening doxorubicin anticancer efficacy.

PMID- 29381816
TI  - Preferences for treatment among adolescents with Type 1 diabetes: a national
      study using a discrete choice experiment model.
AB  - AIM: To test the possibility of using a discrete choice experiment model, on a
      national level in adolescents with Type 1 diabetes, in order to obtain a better
      understanding of drivers of and barriers to diabetes self-care. METHODS: A survey
      instrument was constructed and tested on a small group of the target population:
      adolescents aged 15 to <18 years with Type 1 diabetes. All individuals in Sweden
      belonging to this target group (N=2112) were then identified via the Swedish
      paediatric diabetes quality registry SWEDIABKIDS, and were sent an invitation to
      answer an online questionnaire. A valid response for the discrete choice
      experiment analyses was achieved from 431 individuals. RESULTS: The included
      respondents were not statistically different from non-participants in terms of
      age and duration of diabetes, but more young women entered the study and the
      participants had (on average) a significantly lower HbA1c value than the non
      participants. Participants regarded as undesirable both non-severe hypoglycaemic
      events (day and night) and hyperglycaemic events. Avoiding weight gain and even
      achieving weight loss were the most important aspects among female respondents,
      who were willing to trade off a substantial level of glycaemic control [13
      mmol/mol (1.2%)] to avoid a weight gain of 3 kg. Hypothetical equipment
      improvements were desired. CONCLUSIONS: The responses may provide useful
      indications of the aspects that the respondents would prioritize given a real
      life dilemma. For treatment effects, stratification along gender lines was
      important, whereas the treatment administration aspects were stratified according
      to treatment type because these aspects are closely related.

PMID- 29381817
TI  - Oscillatory activity in the cortico-basal ganglia-thalamic neural circuits in
      Parkinson's disease.
AB  - Dopamine is an important neurotransmitter that maintains the balance within the
      basal ganglia between the direct pathway, which promotes movement, and the
      indirect pathway, which inhibits movement. Degeneration of dopaminergic neurons
      in the substantia nigra increases the influence of the indirect pathway,
      resulting in motor dysfunction in Parkinson's disease (PD). The direct and
      indirect pathways are composed of basal ganglia and thalamic nuclei, which are
      interconnected via independent parallel loop circuits with cortical areas and
      often referred to as cortico-basal ganglia-thalamic (CBT) neural circuits. CBT
      circuits have been useful in generating hypotheses to describe slowness in PD.
      Recent work has focused on aberrant neural oscillations within CBT circuits.
      Although beta (13-30 Hz) oscillations are a common feature of the CBT network,
      there is growing evidence that abnormally exaggerated beta oscillations, observed
      after dopamine loss in the CBT circuits, may contribute to motor symptoms of PD.
      Disruption of abnormal beta oscillations has been associated with the improvement
      of motor functions during pharmacological treatments, surgical lesions, and
      electrical stimulation. However, it is not clear how abnormal oscillations
      originate in the CBT motor network and resonate specifically in the beta band
      after the loss of dopamine. Most studies have addressed these questions by
      simultaneous recordings of oscillations in the motor cortex, basal ganglia
      nuclei, and motor regions of the thalamus in animal models of parkinsonism as
      well as in PD patients. This review further discusses previous and current
      studies of the changes in oscillatory activity at the level of CBT neural network
      in PD.

PMID- 29381818
TI  - Role of omalizumab in insulin hypersensitivity: a case report and review of the
      literature.
AB  - BACKGROUND: Insulin allergy is a rare yet severe side effect of exogenous insulin
      use. Management typically involves use of alternative antihyperglycaemic agents,
      symptom control with antihistamines, use of different insulin formulations, and
      induction of tolerance with incremental doses of insulin. This treatment regimen
      is not always successful, and the use of omalizumab, an anti-IgE monoclonal
      antibody, has been used to induce tolerance to insulin. CASE REPORT: G.M. is a 62
      year-old man with Type 2 diabetes mellitus. His condition was not optimized on
      oral agents, and insulin therapy was required. G.M. had anaphylaxis to insulin
      NPH, and subsequent skin-prick testing was positive to insulin aspart, insulin
      NPH, insulin glulisine, insulin detemir, regular insulin, insulin glargine 100
      units/ml and insulin glargine 300 units/ml. He received incremental doses of
      several insulin formulations; however, he experienced diffuse urticaria
      preventing optimal glycaemic control. Three successful cases have been described
      in the literature of omalizumab inducing tolerance to exogenous insulin;
      therefore, G.M. was started on omalizumab. He subsequently tolerated treatment
      doses of insulin glulisine and insulin detemir with no allergic reactions and
      with improvement in glycaemic control. CONCLUSION: To our knowledge, this is the
      first described case of allergy to insulin glargine 300 units/ml and reiterates
      the potential use of omalizumab in insulin allergy. Further research is warranted
      to determine if omalizumab should be considered standard of care in difficult-to
      treat insulin hypersensitivity.

PMID- 29381819
TI  - Behavioural signatures of backward planning in animals.
AB  - Goal-directed planning in behavioural and neural sciences is theorized to involve
      a prospective mental simulation that, starting from the animal's current state in
      the environment, expands a decision tree in a forward fashion. Backward planning
      in the artificial intelligence literature, however, suggests that agents expand a
      mental tree in a backward fashion starting from a certain goal state they have in
      mind. Here, we show that several behavioural patterns observed in animals and
      humans, namely outcome-specific Pavlovian-to-instrumental transfer and
      differential outcome effect, can be parsimoniously explained by backward
      planning. Our basic assumption is that the presentation of a cue that has been
      associated with a certain outcome triggers backward planning from that outcome
      state. On the basis of evidence pointing to forward and backward planning models,
      we discuss the possibility of brain using a bidirectional planning mechanism
      where forward and backward trees are expanded in parallel to achieve higher
      efficiency.

PMID- 29381820
TI  - Reference tissue models in the assessment of 11 C-DTBZ binding to the VMAT2 in
      rat striatum: A test-retest reproducibility study.
AB  - Dopaminergic PET imaging is a useful tool to assess the dopaminergic integrity
      and to follow-up longitudinal studies. The aim of this study was to evaluate the
      reliability and reproducibility of different reference tissue-based methods to
      determine the non-displaceable binding potential (BPND ) as a quantitative
      measure of 11 C-DTBZ binding to the VMAT2 in rat striatum using cerebellum as
      reference region. Eight healthy Wistar rats underwent two microPET scans at the
      age of 12 (test) and 20 weeks (retest). BPND was determined using the simplified
      reference tissue model, Logan reference tissue model, and multilinear reference
      tissue models (MRTMo and MRTM2). Additionally, a striatal-to-cerebellar-ratio
      (SCR) analysis was performed. The reproducibility between the two scans was
      assessed using the interclass correlation coefficients (ICC) and the variability
      index. Repeatability indices showed acceptable ICC = 0.66 (SCR) to excellent ICC
      = 0.98 (MRTM2) reliability for this study and a variability ranging from 12.26%
      (SCR) to 3.28% (MRTM2). To the best of our knowledge, this is the first report on
      longitudinal studies for 11 C-DTBZ in rats using reference tissue methods.
      Excellent intersubject and intrasubject reproducibility was obtained with the
      multilinear reference MRTM2, suggesting this as the best method to compare
      longitudinal studies, whereas the SCR method had poor reliability. Logan method,
      however, is a method simple to compute that shows accurate reproducibility with a
      reasonable level of inter- and intra-subject variability allowing crossover
      studies to follow-up the uptake of 11 C-DTBZ in rat striatum.

PMID- 29381822
TI  - Metabolomic response to coffee consumption: application to a three-stage clinical
      trial.
AB  - BACKGROUND: Coffee is widely consumed and contains many bioactive compounds, any
      of which may impact pathways related to disease development. OBJECTIVE: To
      identify individual metabolite changes in response to coffee. METHODS: We
      profiled the metabolome of fasting serum samples collected from a previously
      reported single-blinded, three-stage clinical trial. Forty-seven habitual coffee
      consumers refrained from drinking coffee for 1 month, consumed four cups of
      coffee/day in the second month and eight cups/day in the third month. Samples
      collected after each coffee stage were subject to nontargeted metabolomic
      profiling using UPLC-ESI-MS/MS. A total of 733 metabolites were included for
      univariate and multivariate analyses. RESULTS: A total of 115 metabolites were
      significantly associated with coffee intake (P < 0.05 and Q < 0.05). Eighty-two
      were of known identity and mapped to one of 33 predefined biological pathways. We
      observed a significant enrichment of metabolite members of five pathways (P <
      0.05): (i) xanthine metabolism: includes caffeine metabolites, (ii) benzoate
      metabolism: reflects polyphenol metabolite products of gut microbiota metabolism,
      (iii) steroid: novel but may reflect phytosterol content of coffee, (iv) fatty
      acid metabolism (acylcholine): novel link to coffee and (v) endocannabinoid:
      novel link to coffee. CONCLUSIONS: The novel metabolites and candidate pathways
      we have identified may provide new insight into the mechanisms by which coffee
      may be exerting its health effects.

PMID- 29381821
TI  - Ticagrelor attenuates myocardial ischaemia-reperfusion injury possibly through
      downregulating galectin-3 expression in the infarct area of rats.
AB  - AIMS: The full benefits of myocardial revascularization strategies applied to
      acute myocardial infarction patients might be reduced by myocardial ischaemia and
      reperfusion (I/R) injury. It is known that inflammation plays an important role
      in the pathogenesis of I/R injury and galectin-3, a known inflammatory factor, is
      actively involved in ischaemia-induced inflammation and fibrosis of various
      organs. Previous studies demonstrated that anti-platelets therapy with
      ticagrelor, a new P2Y12 receptor antagonist, could effectively attenuate
      myocardial I/R injury and I/R injury-related inflammatory responses. It remains
      unknown whether the cardioprotective effects of ticagrelor are also mediated by
      modulating myocardial galectin-3 expression. METHODS: We determined the ratio of
      infarct area (IA)/area at risk (AAR), expression of galectin-3, TNF-alpha and IL
      6 in infarct area of rats treated with placebo (equal volume saline per gastric
      gavage immediately after LAD ligation, then once daily till study end) or
      ticagrelor (150 mg kg-1 dissolved in saline per gastric gavage immediately after
      LAD ligation, then once daily till study end) at 24 h, 3 and 7 days post I (45
      min)/R injury. Sham-operated rats served as control. RESULTS: Our results showed
      that ticagrelor treatment significantly reduced IA/AAR ratio at 3 and 7 days post
      I/R, downregulated mRNA and protein expression of galectin-3, as well as mRNA
      expression of TNF-alpha and IL-6 in infarct area at 24 h, 3 and 7 days post I/R.
      CONCLUSIONS: Our results suggest that the cardioprotective effects of ticagrelor
      might partly be mediated by downregulating galectin-3 expression in infarct area
      in this rat model of myocardial I/R injury.

PMID- 29381823
TI  - The role of alpha oscillations in distractor inhibition during memory retention.
AB  - Only small amounts of visual information, as determined by the capacity of
      working memory, can be held in an active and accessible state. Thus, it is
      important to select and maintain information that is relevant while ignoring
      irrelevant information. However, the underlying neural mechanism of these
      processes has yet to be identified. One potential candidate are alpha
      oscillations (8-14 Hz), which have been shown to inhibit stimulus processing in
      perceptual tasks. During memory maintenance, alpha power increases with set size
      suggesting that alpha oscillations are involved either in memory maintenance or
      in the inhibition of task-irrelevant information to protect relevant information
      from interference. The need for such a protection should increase with the amount
      of distracting information, but most previous studies did not show any
      distractors. Therefore, we directly tested whether alpha oscillations are
      involved in inhibition of distractors during memory maintenance. Participants
      memorized the orientation of one or two target lines embedded among irrelevant
      distractors. Distractors were either strong or weak and were present during the
      retention interval after which participants reported the orientation of probed
      targets. Computational modeling showed that performance decreased with increasing
      set size and stronger distraction. Alpha power in the retention interval
      generally increased with set size, replicating previous studies. However, here
      stronger distractors reduced alpha power. This finding is in clear
      contradistinction to previous suggestions, as alpha power decrease indicates
      higher neuronal excitability. Thus, our data do not support the suggested role of
      alpha oscillations in inhibition of distraction in working memory.

PMID- 29381824
TI  - Transversus abdominis plane (TAP) block in laparoscopic colorectal surgery
      improves postoperative pain management: a meta-analysis.
AB  - AIM: Transversus abdominis plane (TAP) block is a locoregional anaesthesia
      technique of growing interest in abdominal surgery. However, its efficacy
      following laparoscopic colorectal surgery is still debated. This meta-analysis
      aimed to assess the efficacy of TAP block after laparoscopic colorectal surgery.
      METHOD: All comparative studies focusing on TAP block after laparoscopic
      colorectal surgery have been systematically identified through the MEDLINE
      database, reviewed and included. Meta-analysis was performed according to the
      Mantel-Haenszel method for random effects. End-points included postoperative
      opioid consumption, morbidity, time to first bowel movement and length of
      hospital stay. RESULTS: A total of 13 studies, including 7 randomized controlled
      trials, were included, comprising a total of 600 patients who underwent
      laparoscopic colorectal surgery with TAP block, compared with 762 patients
      without TAP block. Meta-analysis of these studies showed that TAP block was
      associated with a significantly reduced postoperative opioid consumption on the
      first day after surgery [weighted mean difference (WMD) -14.54 (-25.14; -3.94); P
      = 0.007] and a significantly shorter time to first bowel movement [WMD -0.53 (
      0.61; -0.44); P < 0.001] but failed to show any impact on length of hospital stay
      [WMD -0.32 (-0.83; 0.20); P = 0.23] although no study considered length of stay
      as its primary outcome. Finally, TAP block was not associated with a significant
      increase in the postoperative overall complication rate [OR = 0.84 (0.62-1.14); P
      = 0.27]. CONCLUSION: Transversus abdominis plane (TAP) block in laparoscopic
      colorectal surgery improves postoperative opioid consumption and recovery of
      postoperative digestive function without any significant drawback.

PMID- 29381825
TI  - Proton pump inhibitors, Enterococcus, and the liver, oh my!

PMID- 29381827
TI  - Effects of nutrition and hygiene education on oral health and growth among
      toddlers in rural Uganda: follow-up of a cluster-randomised controlled trial.
AB  - OBJECTIVE: To examine the effect of a nutrition and hygiene education
      intervention on oral health behaviour and whether early onset of caries was
      related to child growth in rural Uganda. METHODS: Follow-up study of a cluster
      randomised controlled trial conducted between October 2013 and January 2015. Data
      were available from 399 mother/child pairs (203 in the intervention and 198 in
      the control group) of the original trial (78%) when the children were 36 months
      old. Oral health behaviour was evaluated using questionnaires. Photographs of the
      maxillary anterior teeth were examined for unmistakably carious lesions, and 115
      water samples from the study area were analysed for fluoride concentration.
      RESULTS: The frequency of cleaning of the child's teeth at 36 months was about
      twice as high in the intervention as in the control group (84.3% vs. 46.6%; P =
      0.0001). Cavitated carious lesions occurred more frequently in the control than
      the intervention group (27.8% vs. 18.2%; P = 0.04). Extraction of 'false teeth'
      (ebiino), a painful and crude traditional operation, was profoundly reduced in
      the intervention group (8.9% vs. 24.7%; P = 0.001). There was no evidence of
      association between the occurrence of caries and child growth. CONCLUSIONS: The
      education intervention improved oral hygiene practices and reduced the
      development and progression of caries and extraction of ebiino. Early childhood
      caries was not clearly associated with child growth.

PMID- 29381826
TI  - The effect of itraconazole and rifampicin on the pharmacokinetics of osimertinib.
AB  - AIMS: We investigated the effects of a strong CYP3A4 inhibitor (itraconazole) or
      inducer (rifampicin) on the pharmacokinetics of the epidermal growth factor
      receptor-tyrosine kinase inhibitor osimertinib, in patients with advanced non
      small cell lung cancer in two Phase I, open-label, two-part clinical studies.
      Part one of both studies is reported. METHODS: In the itraconazole study
      (NCT02157883), patients received single-dose osimertinib 80 mg on Days 1 and 10
      and itraconazole (200 mg twice daily) on Days 6-18 orally. In the rifampicin
      study (NCT02197247), patients received osimertinib 80 mg once daily on Days 1-77
      and rifampicin 600 mg once daily on Days 29-49. RESULTS: In the itraconazole
      study (n = 36), the geometric least squares mean (GMLSM) ratios (osimertinib plus
      itraconazole/osimertinib alone) for Cmax and AUC were 80% (90% CI 73, 87) and
      124% (90% CI 115, 135), respectively, below the predefined no-effect upper limit
      of 200%. In the rifampicin study (n = 40), the GMLSM ratios (osimertinib plus
      rifampicin/osimertinib alone) for Css,max and AUCtau were 27% (90% CI 24, 30) and
      22% (90% CI 20, 24), respectively, below the predefined no-effect lower limit of
      50%. The induction effect of rifampicin was apparent within 7 days of initiation;
      osimertinib Css,max and AUCtau values returned to pre-rifampicin levels within 3
      weeks of rifampicin discontinuation. No new osimertinib safety findings were
      observed. CONCLUSIONS: Osimertinib can be co-administered with CYP3A4 inhibitors,
      but strong CYP3A inducers should be avoided if possible.

PMID- 29381828
TI  - Influence of visible light on cutaneous hyperchromias: Clinical efficacy of broad
      spectrum sunscreens.
AB  - INTRODUCTION: Cutaneous hyperchromias are disorders of skin pigmentation
      involving increased melanin production and its irregular accumulation in skin
      cells. The use of sunscreens is fundamental for the control of hyperchromias by
      reducing the stimulation of pigmentation, as melanin synthesis is mainly
      stimulated by solar radiation. Many studies have demonstrated that visible light
      can induce significant skin damage. Considering the effects of visible light,
      effective photoprotection should not be limited only to UV protection but should
      also involve visible and infrared protection. OBJECTIVE: The aim of this study
      was to evaluate the efficacy of UV-VIS sunscreens in protecting skin against
      damages caused by solar radiation and the influence of visible light on the
      appearance of cutaneous hyperchromias. METHODS: Forty volunteers aged 18 to 39
      years with skin hyperpigmentation participated in the study. To evaluate the
      efficacy of the formulations developed, the percentage of hyperpigmented area was
      evaluated using high-resolution images-Visioface(r) Quick (Courage-Khazaka,
      Germany) and the analysis of epidermal pigmentation was performed by RCM
      Vivascope(r) 1500 (Lucid, USA). Also, the melanin index was determined using the
      Mexameter(r) M X16 colorimeter (Courage-Khazaka, Germany). RESULTS: The developed
      formulations were effective in the reduction in melanin index, epidermal
      pigmentation, and percentage of hyperpigmented area. CONCLUSION: Finally, this
      study discusses how the combination of UV filters and pigments can protect the
      skin from solar radiation and reduces skin hyperpigmentations.

PMID- 29381829
TI  - Maternal L-carnitine supplementation improves glucose and lipid profiles in
      female offspring of dams exposed to cigarette smoke.
AB  - Sex differences in disease susceptibility due to maternal programming have been
      reported. We previously observed that maternal smoking induced renal disease and
      neurological changes are restricted to males, while both male and female
      offspring develop metabolic disorders. We have also found that maternal L
      carnitine supplementation during gestation and lactation can significantly
      improve glucose intolerance and hyperlipidaemia in male offspring. This study
      aimed to determine whether such beneficial effects can also occur in female
      offspring. Balb/c female mice were exposed to cigarette smoke (SE) 6 weeks prior
      to gestation, during gestation and lactation. A subgroup of the SE dams was given
      L-carnitine (1.5 mmol/L in drinking water) during gestation and lactation. Female
      offspring were studied at 20 days (weaning) and 13 weeks (adulthood). Maternal
      smoking increased liver weight (%) and blood glucose levels at 20 days, as well
      as glucose intolerance and plasma triglycerides levels at adulthood (P < .05).
      The hepatic lipid metabolic marker adipose triglyceride lipase was downregulated
      in the SE offspring at 20 days (P < .05). At 13 weeks, the hepatic pro
      inflammatory markers IL-1beta and TNF-alpha mRNA expression were upregulated,
      while the anti-inflammatory marker IL-10 mRNA expression was downregulated in the
      SE offspring (P < .05). Liver fibrosis was apparent at 20 days and 13 weeks.
      Maternal L-carnitine supplementation either normalised or suppressed the
      detrimental effects induced by maternal smoke exposure (P < .05). We conclude
      that maternal L-carnitine supplementation improves metabolic parameters in the
      female offspring of SE dams.

PMID- 29381830
TI  - T-cell cross-reactivity may explain the large variation in how cancer patients
      respond to checkpoint inhibitors.
AB  - The therapeutic use of the immune system to specifically attack tumours has been
      a long-standing vision among tumour immunologists. Recently, the use of
      checkpoint inhibitors to turn-off immunosuppressive signals has proven to be
      effective in enhancing T-cell reactivity against patient-specific neoantigens,
      resulting from somatic mutations. Several of the identified T-cell epitopes share
      similarity with common bacterial and viral antigens, suggesting the involvement
      of pre-existing microbial cross-reactive T cells in rapid and durable tumour
      regression seen in some patients. This notion of T-cell cross-reactivity is
      further supported by the findings that intestinal bacteria can influence
      checkpoint-blockade therapy. Moreover, early data indicate the presence of such T
      cells in long-term survival breast cancer patients. This review highlights the
      main challenges for cancer immunotherapy and discusses the potential contribution
      of T-cell cross-reactivity in cancer immunotherapy and whether it can be used as
      a biomarker to predict the responsiveness to checkpoint inhibitors.

PMID- 29381831
TI  - Ptrf transgenic mice exhibit obesity and fatty liver.
AB  - Polymerase I and transcript release factor (Ptrf, also known as Cavin1) is an
      essential component in the biogenesis and function of caveolae. Ptrf knockout
      mice or patients with PTRF mutations exhibit numerous pathologies including
      markedly aberrant fuel metabolism, lipodystrophy and muscular dystrophy. In this
      study, we generated Ptrf transgenic mice to explore its function in vivo.
      Compared with wild-type (WT) mice, we found that the Ptrf transgenic mice showed
      obesity with an increased level of ALT (alanine aminotransferase) and AST
      (aspartate transaminase). Ptrf transgenic mice exhibited severe fat degeneration
      and a higher degree of fat accumulation in the liver compared with WT mice.
      Consistently, we found that the expression of the fat synthesis gene, Fasn, was
      increased in the liver of Ptrf transgenic mice. Thus, Ptrf transgenic mice would
      be a good model for investigating the molecular mechanism and therapeutic targets
      of obesity and fatty liver associated diseases.

PMID- 29381832
TI  - Do not disregard diagnostic clues of endocarditis: comment on the article by Garg
      et al.
AB  - We read with great interest the Clinicopathologic Conference by Garg et al.
      published recently in Arthritis Care & Research about a patient with Bartonella
      related endocarditis (1). However, we regret that the 'petechial pruritic rash'
      on the lower extremities and the presence of elevated rheumatoid factor were
      initially neglected in a context of glomerulonephritis. Indeed the rash was
      poorly described. This article is protected by copyright. All rights reserved.

PMID- 29381833
TI  - Do not disregard diagnostic clues of endocarditis: Reply to comment on the
      article by Garg et al.
AB  - The presentation of endocarditis with a cutaneous vasculitis has been well
      reported. The concern of your team regarding the description of the rash is valid
      but as noted in the case that the rash was part of his past presentation which
      unfortunately was at a different hospital. Given the patient was transferred to
      our hospital with altered mental status, it was difficult to get detailed past
      history in regards of the distribution, symmetry and characteristics of the skin
      rash. This article is protected by copyright. All rights reserved.

PMID- 29381834
TI  - Occupational Therapy Treatment to Improve Upper Extremity Function in Individuals
      with Early Systemic Sclerosis: A Pilot Study.
AB  - OBJECTIVE: To determine the feasibility and preliminary effects of occupational
      therapy to improve upper extremity function in patients with early systemic
      sclerosis (SSc; scleroderma) who have upper extremity contractures. METHODS: A
      single-group pilot clinical rehabilitation trial was conducted at the University
      of Michigan Scleroderma Center. Patients with SSc and >=1 upper extremity
      contracture (n = 21) participated in a total of 8 weekly in-person occupational
      therapy sessions. The therapy consisted of thermal modalities, tissue
      mobilization, and upper extremity mobility exercises. The participants were
      instructed to perform upper extremity exercises at home between sessions.
      Feasibility was measured by the percent enrollment as well as session attendance
      and session duration. The primary outcome measure was the Shortened Disabilities
      of the Arm, Shoulder and Hand measure (QuickDASH); secondary and exploratory
      outcomes included the Patient-Reported Outcomes Measurement Information System
      (PROMIS) physical function measures; objective measures of upper extremity
      mobility, strength, and coordination; and skin thickening. Linear mixed models
      were used to determine the effects of treatment on the primary and secondary
      outcomes. RESULTS: Fifty percent of potentially eligible subjects (24 of 48) were
      interested in participating. Twenty-one (88%) of the 24 subjects were enrolled,
      and 19 (91%) of these 21 subjects completed all sessions. The mean +/- SD age of
      the participants was 47.9 +/- 16.1 years; 100% had diffuse SSc, and the mean
      disease duration was 3.1 years. At 8 weeks, participants had statistically
      significant improvement in the QuickDASH and PROMIS physical function measure (P
      = 0.0012 and P = 0.004, respectively). Approximately one-half of participants in
      the sample achieved improvement in the QuickDASH and PROMIS measure that exceeded
      minimally important differences. CONCLUSION: In-person treatment sessions were
      feasible in the patients with SSc and resulted in statistically significant and
      clinically meaningful improvements in upper extremity and physical function. In
      future studies, the effects of SSc should be compared with those in a control
      condition, and the durability of treatment effects should be examined.

PMID- 29381835
TI  - Ethnographic Observational Study of the Biologic Initiation Conversation Between
      Rheumatologists and Biologic-Naive Rheumatoid Arthritis Patients.
AB  - OBJECTIVE: This ethnographic market research study investigated the biologic
      initiation conversation between rheumatologists and biologic-naive patients with
      rheumatoid arthritis to assess how therapy options, particularly mode of
      administration, were discussed. METHODS: Consenting rheumatologists (n = 16) and
      patients (n = 48) were videotaped during medical visits and interviewed by a
      trained ethnographer. The content, structure, and timing of conversations
      regarding biologic initiation were analyzed. RESULTS: The mean duration of
      physician-patient visits was approximately 15 minutes; biologic therapies were
      discussed for a mean of 5.6 minutes. Subcutaneous (SC) and intravenous (IV)
      therapy options were mentioned in 45 and 35 visits, respectively, out of a total
      of 48 visits. All patients had some familiarity with SC administration, but
      nearly half of patients (22 of 48) were unfamiliar with IV therapy going into the
      visit. IV administration was not defined or described by rheumatologists in 77%
      of visits (27 of 35) mentioning IV therapy. Thus, 19 of 22 patients who were
      initially unfamiliar with IV therapy remained unfamiliar after the visit.
      Disparities in physician-patient perceptions were revealed, as all
      rheumatologists (16 of 16) believed IV therapy would be less convenient than SC
      therapy for patients, while 46% of patients (22 of 48) felt this way. In post
      visit interviews, some patients seemed confused and overwhelmed, particularly
      when presented with many treatment choices in a visit. Some patients stated they
      would benefit from visual aids or summary sheets of key points. CONCLUSION: This
      study revealed significant educational opportunities to improve the biologic
      initiation conversation and indicated a disparity between patients' and
      rheumatologists' perception of IV therapy.

PMID- 29381836
TI  - Skin Induration in a Patient With Aplastic Anemia.

PMID- 29381837
TI  - Ossification Pattern in Forelimbs of the Siamese Crocodile (Crocodylus
      siamensis): Similarity in Ontogeny of Carpus Among Crocodylian Species.
AB  - Crocodylians have highly derived elongated carpus, which is related to their use
      of forelimbs in many types of gaits as well as in burrowing. The objective of
      present study was to describe the ossification of the forelimb in five stages of
      Siamese crocodile (Crocodylus siamensis). The ossification begins approximately
      at stage 20 in arm and forearm bones moving sequentially to the metacarpal
      elements. The first carpal elements with ossification centers are radiale +
      intermedium and ulnare (stage 22-23), and their ossification mode is typical of
      long bones. Between stages 22 and 24 distal carpals 3, 4, and 5 fuse together to
      a single formation. In the stage 25, the ossification proceeds to the pisiform,
      which starts ossifying late during the embryogenesis. The phalangeal formula of
      the digits is 2,3,4,5,3. Although there are some interspecific differences, it
      appears that all crocodylians have similarly uniform skeletal pattern, the
      process of ossification, number of carpal elements and phalangeal formulas
      probably due to their similar lifestyles. Anat Rec, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29381838
TI  - Supporting Arthritis and Employment Across the Life Course: A Qualitative Study.
AB  - OBJECTIVE: To examine the need for and availability and use of formal and
      informal workplace resources and to uncover differences across the life course in
      adults with arthritis. METHODS: Focus groups and interviews were conducted with
      young (aged 18-34 years; n = 7), middle-aged (35-54 years; n = 13), and older
      adults (>=55 years; n = 25) with a diagnosis of inflammatory arthritis,
      osteoarthritis, or other rheumatic disease. Participants were asked about their
      employment experiences, formal and informal workplace resource needs, and
      availability and use of workplace resources. Differences based on chronological,
      functional, psychosocial, organizational, and lifespan dimensions of age were
      examined. A modified grounded theory approach was used to inductively analyze the
      data. RESULTS: Young, middle-aged, and older adult participants required similar
      workplace resources. Across all participants, scheduling modifications tended to
      be the most needed workplace resource. In contrast, the perceived availability
      and use of formal workplace resources differed among participants. Young adult
      participants and those who were newer to their jobs reported that workplace
      resources were less available and utilized. Middle-aged and older adults reported
      greater availability of workplace resources. Scheduling accommodations and at
      work modifications were the workplace resources that were used most by middle
      aged and older adults, respectively. CONCLUSION: Similar workplace resources
      could meet the employment needs of individuals with arthritis across the life
      course. Attention should be paid to young adults and those who are new to their
      jobs, because they may perceive more barriers to accessing formal workplace
      resources and be susceptible to work disability.

PMID- 29381839
TI  - High-sensitivity 5-, 6-, and 7-color PNH WBC assays for both Canto II and Navios
      platforms.
AB  - BACKGROUND: Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare acquired
      hematopoietic stem cell disorder characterized by an inability to make Glyco
      Phosphatidyl-Inositol (GPI)-linked cell surface structures. Fluorescent
      proaerolysin (FLAER-Alexa488) is increasingly used to detect GPI-deficient WBCs
      by flow cytometry. However, FLAER is not available in all countries and is
      expensive to obtain in others. An earlier study to compare FLAER-based and non
      FLAER assays confirmed very good agreement between the two tubes suggesting a
      cost effective simultaneous evaluation of PNH neutrophils and monocytes is
      possible without FLAER. METHODS: We have used a single tube approach with a 7
      color assay comprising FLAER-CD157-CD15-CD64-CD24-CD14-CD45. Conjugates were
      carefully selected and validated so that stained samples could be analyzed on
      either 10-color Navios or 8-color FACSCanto II platforms. The 6-color (minus
      CD14) and 5-color (minus CD24 and CD14) versions were also developed and compared
      with our predicate clinical lab 5-color assay comprising FLAER-CD157PE-CD64ECD
      CD15PC5-CD45PC7. RESULTS/CONCLUSIONS: CD15-gated PNH neutrophil clone size was
      quantified using either FLAER and CD157, FLAER and CD24, or CD157 and CD24. CD64
      gated PNH monocyte clone size was quantified using either FLAER and CD157, FLAER
      and CD14, or CD157 and CD14. Analysis of >40 PNH samples showed that the FLAER
      based plots derive virtually identical data to the non-FLAER plot for neutrophils
      (R2  = 1) and monocytes (R2  = 0.9999) and that closely similar data can be
      acquired using both Canto II and Navios platforms with 7-, 6-, and 5-color
      versions of the assay. Assessment of non-PNH samples confirmed extremely low
      background rate of PNH phenotypes (neutrophils and monocytes) with all three
      approaches. (c) 2018 International Clinical Cytometry Society.

PMID- 29381840
TI  - Swimming Against the Current: A Qualitative Review of the Work Experiences and
      Adaptations Made by Employees With Arthritis.
AB  - OBJECTIVE: To describe the experiences and strategies of employees with arthritis
      to maintain employment, and to use this information to build a conceptual model.
      METHODS: We conducted a systematic review of qualitative studies that examined
      the work experiences of employees with arthritis. Published studies on arthritis
      and employment were searched from electronic databases (1980-2017) and
      bibliographic reviews of relevant studies. We used meta-ethnography to synthesize
      the findings. RESULTS: We reviewed 17 studies that reported on the experiences of
      873 employees. We identified 11 main themes that highlight common issues
      experienced by employees with arthritis and grouped these into 4 higher-order
      categories: changing nature of the disease (emotional issues, cognitive
      struggles, unpredictable physical symptoms), intrapersonal issues (personal
      meaning of work, preserving a work identity), interpersonal issues (managing
      disclosure, gaining coworker support, organizational culture issues), and work
      sustainability strategies (making personal adjustments, using social support,
      using workplace accommodations). Using these themes, we developed the Job
      Sustainability Model to illustrate how disease, personal, and work-related
      factors interact to influence what type of coping behaviors are used and when.
      Initially, employees with arthritis rely on making personal adjustments, using
      social support, and medical intervention. However, when these coping behaviors
      fail to be effective, they draw upon workplace accommodations and resources.
      CONCLUSION: Arthritis disrupts an employee's work life by impairing his or her
      capacity to be a productive worker. Our results highlight how employees with
      arthritis make strategic adaptations to maintain a productive work life for as
      long as possible. The findings of this study have implications for work-related
      interventions aimed at preserving employment.

PMID- 29381841
TI  - Editorial: Epratuzumab: Reveille or Requiem? Teachable Moments for Lupus and
      Sjogren's Syndrome Clinical Trials.

PMID- 29381842
TI  - Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of
      Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission.
AB  - OBJECTIVE: To examine the expression and changes in function of circulating
      CD4+CXCR5+FoxP3+ follicular Treg (Tfr) cells in patients with active rheumatoid
      arthritis (RA) and in patients with RA in stable remission, and to clarify the
      role of Tfr cells in the pathogenesis of RA. METHODS: Levels of Tfr cells and
      follicular helper T (Tfh) cells in the peripheral blood of 39 patients with
      active RA, 39 patients with RA in stable remission, and 33 healthy controls were
      detected by flow cytometry. The function of Tfr cells was measured by coculturing
      them with Tfh cells and B cells. Activated CD45RA-FoxP3high Tfr cells were also
      analyzed. Clinical indicators, including serum Ig and autoantibody levels, were
      tested, and correlations with Tfr cells were systematically analyzed. The Disease
      Activity Score in 28 joints (DAS28) was calculated, and correlation analysis with
      Tfr cells was conducted. RESULTS: The level of CD4+CXCR5+FoxP3+ Tfr cells and the
      Tfr cell:Tfh cell ratio in peripheral blood from patients with RA in stable
      remission were significantly increased compared with the same measures in
      patients with active RA and in healthy controls. The function of Tfr cells was
      enhanced, and the activated CD45RA-FoxP3high Tfr cell subset was increased in
      patients with RA in stable remission compared with healthy controls. Furthermore,
      the number of Tfr cells in RA patients was inversely correlated with IgG,
      rheumatoid factor, and anti-cyclic citrullinated peptide as well as with the
      DAS28. CONCLUSION: Circulating Tfr cells are increased as patients with RA
      achieve stable remission of disease, and increased Tfr cells can suppress
      autoimmunity in RA patients to stabilize their condition. Our results provide
      novel insight into RA pathogenesis.

PMID- 29381844
TI  - ?

PMID- 29381843
TI  - Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus
      Erythematosus Patients With Associated Sjogren's Syndrome: Post Hoc Analyses From
      the EMBODY Trials.
AB  - OBJECTIVE: EMBODY 1 (ClinicalTrials.gov identifier: NCT01262365) and EMBODY 2
      (ClinicalTrials.gov identifier: NCT01261793) investigated the efficacy and safety
      of epratuzumab, a CD22-targeted humanized monoclonal IgG antibody, in patients
      with systemic lupus erythematosus (SLE). The studies showed no significant
      difference from placebo in primary or secondary clinical outcome measures but did
      demonstrate B cell-specific immunologic activity. The aim of this post hoc
      analysis was to determine whether epratuzumab had a different clinical efficacy
      profile in SLE patients with versus those without an associated diagnosis of
      Sjogren's syndrome (SS). METHODS: The efficacy and safety of epratuzumab were
      compared between 2 patient subpopulations randomized in EMBODY 1 and 2: SLE
      patients with and those without a diagnosis of associated SS. British Isles Lupus
      Assessment Group (BILAG) total score, BILAG-based Combined Lupus Assessment
      (BICLA) clinical response to treatment, biologic markers (including B cells, IgG,
      IgM, and IgA), and safety were assessed. RESULTS: A total of 1,584 patients were
      randomized in the EMBODY 1 and EMBODY 2 trials; 113 patients were anti-SSA
      positive and had a diagnosis of associated SS, and 1,375 patients (86.8%) had no
      diagnosis of associated SS (918 patients were randomized to receive epratuzumab
      and 457 to receive placebo). For patients with associated SS, but not those
      without associated SS, a higher proportion of patients receiving epratuzumab
      achieved a BICLA response and a reduction from baseline in BILAG total score. B
      cell reduction was faster in patients with associated SS. The sensitivity of B
      cells to epratuzumab as measured by the mean concentration producing 50% of the
      maximum B cell count depletion was lower for patients with associated SS (9.5
      MUg/ml) versus the total EMBODY population (87.1 MUg/ml). No difference in the
      frequency of adverse events in those receiving placebo was reported. CONCLUSION:
      Patients with SLE and associated SS treated with epratuzumab showed improvement
      in SLE disease activity, which was associated with bioactivity, such as decreases
      in B cell number and IgM level.

PMID- 29381845
TI  - ?

PMID- 29381846
TI  - ?

PMID- 29381847
TI  - ?

PMID- 29381848
TI  - ?

PMID- 29381849
TI  - ?

PMID- 29381850
TI  - ?

PMID- 29381851
TI  - ?

PMID- 29381852
TI  - Comparison between Soil- and Biochar-Derived Humic Acids: Composition,
      Conformation, and Phenanthrene Sorption.
AB  - Biochar-derived organic matter (BDOM) plays an important role in determining
      biochar's application potential in soil remediation. However, little is known
      about the physicochemical properties of BDOM and its sorption of hydrophobic
      organic compounds (HOCs). Humic acids (HAs) were extracted from oxidized biochars
      produced from plant straws and animal manures at 450  degrees C, and their
      sorption of phenanthrene, a representative of HOCs, was investigated. The organic
      carbon recovery of biochar-derived HAs (BDHAs) was 13.9-69.3%. The 13C NMR
      spectra of BDHAs mainly consisted of aromatic and carboxylic C, while those of
      soil-derived HAs (SDHAs) contained abundant signals in aliphatic region. BDHAs
      and SDHAs had comparable CO2 cumulative surface areas. BDHAs were found to
      exhibit higher phenanthrene sorption than SDHAs. After the removal of amorphous
      aromatic components, the logKoc values of BDHAs were significantly decreased,
      implying that amorphous aromatic C regulated phenanthrene sorption by BDHAs. In
      contrast, aliphatic moieties dominated phenanthrene sorption by SDHAs, as
      evidenced by the enhanced sorption after the removal of amorphous aromatics. This
      study clearly demonstrated the contrasting characteristics and sorption behaviors
      of BDHA and SDHA, indicating that biochar addition and subsequent weathering
      could greatly affect native organic matter properties and the fate of HOCs in
      biochar-amended soils.

PMID- 29381853
TI  - Hierarchical On-Surface Synthesis of Graphene Nanoribbon Heterojunctions.
AB  - Bottom-up graphene nanoribbon (GNR) heterojunctions are nanoscale strips of
      graphene whose electronic structure abruptly changes across a covalently bonded
      interface. Their rational design offers opportunities for profound technological
      advancements enabled by their extraordinary structural and electronic properties.
      Thus far, the most critical aspect of their synthesis, the control over sequence
      and position of heterojunctions along the length of a ribbon, has been plagued by
      randomness in monomer sequences emerging from step-growth copolymerization of
      distinct monomers. All bottom-up GNR heterojunction structures created so far
      have exhibited random sequences of heterojunctions and, while useful for
      fundamental scientific studies, are difficult to incorporate into functional
      nanodevices as a result. In contrast, we describe a hierarchical fabrication
      strategy that allows the growth of bottom-up GNRs that preferentially exhibit a
      single heterojunction interface rather than a random statistical sequence of
      junctions along the ribbon. Such heterojunctions provide a viable platform that
      could be directly used in functional GNR-based device applications at the
      molecular scale. Our hierarchical GNR fabrication strategy is based on
      differences in the dissociation energies of C-Br and C-I bonds that allow control
      over the growth sequence of the block copolymers from which GNRs are formed and
      consequently yields a significantly higher proportion of single-junction GNR
      heterostructures. Scanning tunneling spectroscopy and density functional theory
      calculations confirm that hierarchically grown heterojunctions between chevron
      GNR (cGNR) and binaphthyl-cGNR segments exhibit straddling Type I band alignment
      in structures that are only one atomic layer thick and 3 nm in width.

PMID- 29381855
TI  - Controlled Evaluation of the Impacts of Surface Coatings on Silver Nanoparticle
      Dissolution Rates.
AB  - Silver nanoparticles (AgNPs) are increasingly being incorporated into a range of
      consumer products and as such there is significant potential for the
      environmental release of either the AgNPs themselves or Ag+ ions. When AgNPs are
      exposed to environmental systems, the engineered surface coating can potentially
      be displaced or covered by naturally abundant macromolecules. These capping
      agents, either engineered or incidental, potentially block reactants from surface
      sites and can alter nanoparticle transformation rates. We studied how surface
      functionalization affects the dissolution of uniform arrays of AgNPs fabricated
      by nanosphere lithography (NSL). Bovine serum albumin (BSA) and two molecular
      weights of thiolated polyethylene glycol (PEG; 1000 and 5000 Da) were tested as
      model capping agents. Dissolution experiments were conducted in air-saturated
      phosphate buffer containing 550 mM NaCl. Tapping-mode atomic force microscopy
      (AFM) was used to measure changes in AgNP height over time. The measured
      dissolution rate for unfunctionalized AgNPs was 1.69 +/- 0.23 nm/d, while the
      dissolution rates for BSA, PEG1000, and PEG5000 functionalized samples were 0.39
      +/- 0.05, 0.20 +/- 0.10, and 0.14 +/- 0.07 nm/d, respectively. PEG provides a
      steric barrier restricting mass transfer of reactants to sites on the AgNP
      surface and thus diminishes the dissolution rate. The effects of BSA, however,
      are more complicated with BSA initially enhancing dissolution, but providing
      protection against dissolution over extended time.

PMID- 29381854
TI  - Regioselective Synthesis of Pyranone-Fused Indazoles via Reductive Cyclization
      and Alkyne Insertion.
AB  - A novel and efficient method for the one-pot synthesis of 2 H-indazole from
      readily available building blocks is reported. The reaction of 2
      nitrobenzylamines with zinc and ammonium formate underwent partial reduction to
      nitroso-benzylamine followed by an intramolecular cyclization to afford 2 H
      indazole via N-N bond formation. The carboxylic acid moiety of indazole was
      proceeded to regioselective alkyne insertion under ruthenium catalysis to form
      pyranone-fused indazoles. The regioselectivity is influenced by the weak
      coordination of indazole ring nitrogen to the metal center.

PMID- 29381856
TI  - Biochemical Studies and Molecular Dynamic Simulations Reveal the Molecular Basis
      of Conformational Changes in DNA Methyltransferase-1.
AB  - DNA methyltransferase-1 (DNMT1) plays a crucial role in the maintenance of
      genomic methylation patterns. The crystal structure of DNMT1 was determined in
      two different states in which the helix that follows the catalytic loop was
      either kinked (designated helix-kinked) or well folded (designated helix-straight
      state). Here, we show that the proper structural transition between these two
      states is required for DNMT1 activity. The mutations of N1248A and R1279D, which
      did not affect interactions between DNMT1 and substrates or cofactors,
      allosterically reduced enzymatic activities in vitro by decreasing kcat/ Km for
      AdoMet. The crystallographic data combined with molecular dynamic (MD)
      simulations indicated that the N1248A and R1279D mutants bias the catalytic helix
      to either the kinked or straight conformation. In addition, genetic
      complementation assays for the two mutants suggested that disturbing the
      conformational transition reduced DNMT1 activity in cells, which could act
      additively with existing DNMT inhibitors to decrease DNA methylation.
      Collectively, our studies provide molecular insights into conformational changes
      of the catalytic helix, which is essential for DNMT1 catalytic activity, and thus
      aid in better understanding the relationship between DNMT1 dynamic switching and
      enzymatic activity.

PMID- 29381857
TI  - Improved Ionic Diffusion through the Mesoporous Carbon Skin on Silicon
      Nanoparticles Embedded in Carbon for Ultrafast Lithium Storage.
AB  - Because of their combined effects of outstanding mechanical stability, high
      electrical conductivity, and high theoretical capacity, silicon (Si)
      nanoparticles embedded in carbon are a promising candidate as electrode material
      for practical utilization in Li-ion batteries (LIBs) to replace the conventional
      graphite. However, because of the poor ionic diffusion of electrode materials,
      the low-grade ultrafast cycling performance at high current densities remains a
      considerable challenge. In the present study, seeking to improve the ionic
      diffusion, we propose a novel design of mesoporous carbon skin on the Si
      nanoparticles embedded in carbon by hydrothermal reaction, poly(methyl
      methacrylate) coating process, and carbonization. The resultant electrode offers
      a high specific discharge capacity with excellent cycling stability (1140 mA h g
      1 at 100 mA g-1 after 100 cycles), superb high-rate performance (969 mA h g-1 at
      2000 mA g-1), and outstanding ultrafast cycling stability (532 mA h g-1 at 2000
      mA g-1 after 500 cycles). The battery performances are surpassing the previously
      reported results for carbon and Si composite-based electrodes on LIBs. Therefore,
      this novel approach provides multiple benefits in terms of the effective
      accommodation of large volume expansions of the Si nanoparticles, a shorter Li
      ion diffusion pathway, and stable electrochemical conditions from a faster ionic
      diffusion during cycling.

PMID- 29381859
TI  - High-Speed Live-Cell Interferometry: A New Method for Quantifying Tumor Drug
      Resistance and Heterogeneity.
AB  - We report the development of high-speed live-cell interferometry (HSLCI), a new
      multisample, multidrug testing platform for directly measuring tumor therapy
      response via real-time optical cell biomass measurements. As a proof of concept,
      we show that HSLCI rapidly profiles changes in biomass in BRAF inhibitor (BRAFi)
      sensitive parental melanoma cell lines and in their isogenic BRAFi-resistant
      sublines. We show reproducible results from two different HSLCI platforms at two
      institutions that generate biomass kinetic signatures capable of discriminating
      between BRAFi-sensitive and -resistant melanoma cells within 24 h. Like other
      quantitative phase imaging (QPI) modalities, HSLCI is well-suited to noninvasive
      measurements of single cells and cell clusters, requiring no fluorescence or dye
      labeling. HSLCI is substantially faster and more sensitive than field-standard
      growth inhibition assays, and in terms of the number of cells measured
      simultaneously, the number of drugs tested in parallel, and temporal measurement
      range, it exceeds the state of the art by more than 10-fold. The accuracy and
      speed of HSLCI in profiling tumor cell heterogeneity and therapy resistance are
      promising features of potential tools to guide patient therapeutic selections.

PMID- 29381858
TI  - Bioinorganic Explorations of Zn(II) Sequestration by Human S100 Host-Defense
      Proteins.
AB  - The human innate immune system launches a metal-withholding response to starve
      invading microbial pathogens of essential metal nutrients. Zn(II)-sequestering
      proteins of the human S100 family contribute to this process and include
      calprotectin (CP, S100A8/S100A9 oligomer, calgranulin A/B oligomer), S100A12
      (calgranulin C), and S100A7 (psoriasin). This Perspective highlights recent
      advances in the Zn(II) coordination chemistry of these three proteins, as well as
      select studies that evaluate Zn(II) sequestration as an antimicrobial mechanism.

PMID- 29381860
TI  - Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine
      Theranostics.
AB  - To develop a radioactive metal complex platform for tumor theranostics, we
      introduced three radiopharmaceutical derivatives of 1,4,7,10
      tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1)
      labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu).
      The tumor-targeting ability of these complexes was demonstrated in a cellular
      uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa
      cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      complex. According to in vivo positron emission tomography imaging, high
      accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site,
      while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently,
      this molecular platform represents a useful approach in nuclear medicine toward
      tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for
      diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in
      conjunction with each other.

PMID- 29381861
TI  - Discovery of Selective, Substrate-Competitive, and Passive Membrane Permeable
      Glycogen Synthase Kinase-3beta Inhibitors: Synthesis, Biological Evaluation, and
      Molecular Modeling of New C-Glycosylflavones.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a key enzyme responsible for tau
      hyperphosphorylation and is a viable therapeutic target of Alzheimer's disease
      (AD). We developed a new class of GSK-3beta inhibitors based on the 6- C
      glycosylflavone isoorientin (1). The new inhibitors are passive membrane
      permeable and constitutively attenuate GSK-3beta mediated tau
      hyperphosphorylation and amyloid neurotoxicity in an AD cellular model. Enzymatic
      assays and kinetic studies demonstrated that compound 30 is a GSK-3beta substrate
      competitive inhibitor with distinct kinase selectivity, isoform-selectivity and
      over 310-fold increased potency as compared to 1. Structure-activity relationship
      analyses and in silico modeling suggest the mechanism of actions by which the
      hydrophobic, pi-cation, and orthogonal multipolar interactions of 30 with the
      substrate site are critical for the GSK-3beta inhibition and selectivity. The
      results provide new insights into GSK-3beta drug discovery. The new inhibitors
      are valuable chemical probes and drug leads with therapeutic potential to tackle
      AD and other GSK-3beta relevant diseases.

PMID- 29381862
TI  - Atmospheric Reaction of Cl with 4-Hydroxy-2-pentanone (4H2P): A Theoretical
      Study.
AB  - The kinetics and the mechanism of the reaction of 4-hydroxy-2-pentanone (4H2P)
      with Cl atom were investigated using quantum theoretical calculations. Density
      functional theory, CBS-QB3, and G3B3 methods are used to explore the reaction
      pathways. Rice-Ramsperger-Kassel-Marcus theory is employed to obtain rate
      constants of the reaction at atmospheric pressure and the temperature range 278
      400 K. This study provides the first theoretical and kinetic determination of Cl
      rate constant for reactions with 4H2P over a large temperature range. The
      obtained rate constant 1.47 * 10-10 cm3 molecule-1 s-1 at 298 K is in reasonable
      agreement with those obtained for C4-C5 hydroxyketones both theoretically and
      experimentally. The results regarding the structure-reactivity relationship and
      the atmospheric implications are discussed.

PMID- 29381863
TI  - Manipulating the Ordered Nanostructure of Self-Assembled Monoolein and
      Phytantriol Nanoparticles with Unsaturated Fatty Acids.
AB  - Mesophase structures of self-assembled lyotropic liquid crystalline nanoparticles
      are important factors that directly influence their ability to encapsulate and
      release drugs and their biological activities. However, it is difficult to
      predict and precisely control the mesophase behavior of these materials,
      especially in complex systems with several components. In this study, we report
      the controlled manipulation of mesophase structures of monoolein (MO) and
      phytantriol (PHYT) nanoparticles by adding unsaturated fatty acids (FAs). By
      using high throughput formulation and small-angle X-ray scattering
      characterization methods, the effects of FAs chain length, cis-trans isomerism,
      double bond location, and level of chain unsaturation on self-assembled systems
      are determined. Additionally, the influence of temperature on the phase behavior
      of these nanoparticles is analyzed. We found that in general, the addition of
      unsaturated FAs to MO and PHYT induces the formation of mesophases with higher
      Gaussian surface curvatures. As a result, a rich variety of lipid polymorphs are
      found to correspond with the increasing amounts of FAs. These phases include
      inverse bicontinuous cubic, inverse hexagonal, and discrete micellar cubic phases
      and microemulsion. However, there are substantial differences between the phase
      behavior of nanoparticles with trans FA, cis FAs with one double bond, and cis
      FAs with multiple double bonds. Therefore, the material library produced in this
      study will assist the selection and development of nanoparticle-based drug
      delivery systems with desired mesophase.

PMID- 29381864
TI  - Stress Responses of Aquatic Plants to Silver Nanoparticles.
AB  - Silver nanoparticles (AgNPs) are increasingly used in consumer products,
      biotechnology, and medicine, and are released into aquatic ecosystems through
      wastewater discharge. This study investigated the phytotoxicity of AgNPs to
      aquatic plants, Egeria densa and Juncus effusus by measuring physiologic and
      enzymatic responses to AgNP exposure under three release scenarios: two chronic
      (8.7 mg, weekly) exposures to either zerovalent AgNPs or sulfidized silver
      nanoparticles; and a pulsed (450 mg, one-time) exposure to zerovalent AgNPs.
      Plant enzymatic and biochemical stress responses were assessed using superoxide
      dismutase (SOD) and peroxidase (POD) activity, malondialdehyde (MDA)
      concentrations and chlorophyll content as markers of defense and phytotoxicity,
      respectively. The high initial pulse treatment resulted in rapid changes in
      physiological characteristics and silver concentration in plant tissue at the
      beginning of each AgNPs exposure (6 h, 36 h, and 9 days), while continuous AgNP
      and sulfidized AgNP chronic treatments gave delayed responses. Both E. densa and
      J. effusus enhanced their tolerance to AgNPs toxicity by increasing POD and SOD
      activities to scavenge free radicals but at different growth phases. Chlorophyll
      did not change. After AgNPs exposure, MDA, an index of membrane damage, was
      higher in submerged E. densa than emergent J. effusus, which suggested that
      engineered nanoparticles exerted more stress to submerged macrophytes.

PMID- 29381865
TI  - Directly Formed Alucone on Lithium Metal for High-Performance Li Batteries and Li
      S Batteries with High Sulfur Mass Loading.
AB  - Lithium metal is considered the "holy grail" of next-generation battery anodes.
      However, severe parasitic reactions at the lithium-electrolyte interface deplete
      the liquid electrolyte and the uncontrolled formation of high surface area and
      dendritic lithium during cycling causes rapid capacity fading and battery
      failure. Engineering a dendrite-free lithium metal anode is therefore critical
      for the development of long-life batteries using lithium anodes. In this study,
      we deposit a conformal, organic/inorganic hybrid coating, for the first time,
      directly on lithium metal using molecular layer deposition (MLD) to alleviate
      these problems. This hybrid organic/inorganic film with high cross-linking
      structure can stabilize lithium against dendrite growth and minimize side
      reactions, as indicated by scanning electron microscopy. We discovered that the
      alucone coating yielded several times longer cycle life at high current rates
      compared to the uncoated lithium and achieved a steady Coulombic efficiency of
      99.5%, demonstrating that the highly cross-linking structured material with great
      mechanical properties and good flexibility can effectively suppress dendrite
      formation. The protected Li was further evaluated in lithium-sulfur (Li-S)
      batteries with a high sulfur mass loading of ~5 mg/cm2. After 140 cycles at a
      high current rate of ~1 mA/cm2, alucone-coated Li-S batteries delivered a
      capacity of 657.7 mAh/g, 39.5% better than that of a bare lithium-sulfur battery.
      These findings suggest that flexible coating with high cross-linking structure by
      MLD is effective to enable lithium protection and offers a very promising avenue
      for improved performance in the real applications of Li-S batteries.

PMID- 29381866
TI  - Transient Sub-bandgap States in Halide Perovskite Thin Films.
AB  - Metal halide perovskites are promising solar energy materials, but their
      mechanism of action remains poorly understood. It has been conjectured that
      energetically stabilized states such as those corresponding to polarons,
      quasiparticles in which the carriers are dressed with phonons, are responsible
      for their remarkable photophysical properties. Yet, no direct evidence of
      polarons or other low-energy states have been reported despite extensive efforts.
      Such states should manifest as below bandgap features in transient absorption and
      photoluminescence measurements. Here, we use single-particle transient absorption
      microscopy on MAPbI3 (MA = methylammonium) to unambiguously identify spectrally
      narrow sub-bandgap states directly; we demonstrate that such signals are
      completely averaged away in ensemble measurements. Carrier temperature-dependent
      studies suggest that hot carriers are directed toward transient low-energy states
      which are immune from permanent defects and traps, thereby giving rise to low
      carrier recombination rates and ultimately high power conversion efficiency in
      devices. The utilization of short-lived sub-bandgap states may be a key design
      principle that propels widespread use of highly heterogeneous materials in
      optoelectronic applications.

PMID- 29381867
TI  - METLIN: A Technology Platform for Identifying Knowns and Unknowns.
AB  - METLIN originated as a database to characterize known metabolites and has since
      expanded into a technology platform for the identification of known and unknown
      metabolites and other chemical entities. Through this effort it has become a
      comprehensive resource containing over 1 million molecules including lipids,
      amino acids, carbohydrates, toxins, small peptides, and natural products, among
      other classes. METLIN's high-resolution tandem mass spectrometry (MS/MS)
      database, which plays a key role in the identification process, has data
      generated from both reference standards and their labeled stable isotope
      analogues, facilitated by METLIN-guided analysis of isotope-labeled
      microorganisms. The MS/MS data, coupled with the fragment similarity search
      function, expand the tool's capabilities into the identification of unknowns.
      Fragment similarity search is performed independent of the precursor mass,
      relying solely on the fragment ions to identify similar structures within the
      database. Stable isotope data also facilitate characterization by coupling the
      similarity search output with the isotopic m/ z shifts. Examples of both are
      demonstrated here with the characterization of four previously unknown
      metabolites. METLIN also now features in silico MS/MS data, which has been made
      possible through the creation of algorithms trained on METLIN's MS/MS data from
      both standards and their isotope analogues. With these informatic and
      experimental data features, METLIN is being designed to address the
      characterization of known and unknown molecules.

PMID- 29381869
TI  - Role of Solvent Polarity and Hydrogen-Bonding on Excited-State Fluorescence of 3
      [(E)-{4-[Dimethylamino]benzylidene}amino]-2-naphthoic Acid (DMAMN): Isomerization
      vs Rotomerization.
AB  - The present experimental and theoretical study on a new chromophore DMAMN of the
      type push-pi-pull (push = dimethylaniline, pi = imine, pull = 2-naphthoic acid),
      allows understanding of the mechanism by which the molecular conformational
      undergoes isomerization/rotomerization following electronic excitation. The
      steady-state fluorescence spectra of this compound, carried out in solvents of
      different polarities and proticities, showed significant changes in both the
      shape and peak positions. The wavelength and intensity change depend on the
      polarity and hydrogen-bonding environment. In highly polar solvents, the emission
      is weak and red-shifted compared to that for cyclohexane, but it is more red
      shifted in moderate aprotic polar solvents. In hydroxyl solvents, a new weak low
      energy emission band appears at ~525 nm, attributed to the intermolecularly H
      bonded open conformer. On the basis of the generated potential energy landscapes
      of the ground state and low-lying excited state in the gas phase and solution, we
      found that selective photon absorption, brings this molecule to a "bright" state,
      from which N?C isomerization Z -> E, takes place. This isomerization in gas-phase
      and low-polarity solvents leads to two minima with a barrier, whereas in highly
      polar-protic media, it gives one minimum on the S1 surface with low DeltaES1/T1
      (0.17 eV), facilitating deactivation via ISC.

PMID- 29381868
TI  - Photochemical Conversion of Surrogate Emissions for Use in Toxicological Studies:
      Role of Particulate- and Gas-Phase Products.
AB  - The production of photochemical atmospheres under controlled conditions in an
      irradiation chamber permits the manipulation of parameters that influence the
      resulting air-pollutant chemistry and potential biological effects. To date, no
      studies have examined how contrasting atmospheres with a similar Air Quality
      Health Index (AQHI), but with differing ratios of criteria air pollutants, might
      differentially affect health end points. Here, we produced two atmospheres with
      similar AQHIs based on the final concentrations of ozone, nitrogen dioxide, and
      particulate matter (PM2.5). One simulated atmosphere (SA-PM) generated from
      irradiation of ~23 ppmC gasoline, 5 ppmC alpha-pinene, 529 ppb NO, and 3 MUg m-3
      (NH4)2SO4 as a seed resulted in an average of 976 MUg m-3 PM2.5, 326 ppb NO2, and
      141 ppb O3 (AQHI 97.7). The other atmosphere (SA-O3) generated from 8 ppmC
      gasoline, 5 ppmC isoprene, 874 ppb NO, and 2 MUg m-3 (NH4)2SO4 resulted in an
      average of 55 MUg m-3 PM2.5, 643 ppb NO2, and 430 ppb O3 (AQHI of 99.8). Chemical
      speciation by gas chromatography showed that photo-oxidation degraded the organic
      precursors and promoted the de novo formation of secondary reaction products such
      as formaldehyde and acrolein. Further work in accompanying papers describe
      toxicological outcomes from the two distinct photochemical atmospheres.

PMID- 29381870
TI  - Robotically Assisted Sonic Therapy as a Noninvasive Nonthermal Ablation Modality:
      Proof of Concept in a Porcine Liver Model.
AB  - Purpose To determine the feasibility of creating a clinically relevant hepatic
      ablation (ie, an ablation zone capable of treating a 2-cm liver tumor) by using
      robotically assisted sonic therapy (RAST), a noninvasive and nonthermal focused
      ultrasound therapy based on histotripsy. Materials and Methods This study was
      approved by the institutional animal use and care committee. Ten female pigs were
      treated with RAST in a single session with a prescribed 3-cm spherical treatment
      region and immediately underwent abdominal magnetic resonance (MR) imaging. Three
      pigs (acute group) were sacrificed immediately following MR imaging. Seven pigs
      (chronic group) were survived for approximately 4 weeks and were reimaged with MR
      imaging immediately before sacrifice. Animals underwent necropsy and harvesting
      of the liver for histologic evaluation of the ablation zone. RAST ablations were
      performed with a 700-kHz therapy transducer. Student t tests were performed to
      compare prescribed versus achieved ablation diameter, difference of sphericity
      from 1, and change in ablation zone volume from acute to chronic imaging. Results
      Ablation zones had a sphericity index of 0.99 +/- 0.01 (standard deviation) (P <
      .001 vs sphericity index of 1). Anteroposterior and transverse dimensions were
      not significantly different from prescribed (3.4 +/- 0.7; P = .08 and 3.2 +/-
      0.8; P = .29, respectively). The craniocaudal dimension was significantly larger
      than prescribed (3.8 +/- 1.1; P = .04), likely because of respiratory motion. The
      central ablation zone demonstrated complete cell destruction and a zone of
      partial necrosis. A fibrous capsule surrounded the ablation zone by 4 weeks. On 4
      week follow-up images, ablation zone volumes decreased by 64% (P < .001).
      Conclusion RAST is capable of producing clinically relevant ablation zones in a
      noninvasive manner in a porcine model. (c) RSNA, 2018.

PMID- 29381872
TI  - Corrigendum.

PMID- 29381871
TI  - Diffusion Properties and 3D Architecture of Human Lower Leg Muscles Assessed with
      Ultra-High-Field-Strength Diffusion-Tensor MR Imaging and Tractography:
      Reproducibility and Sensitivity to Sex Difference and Intramuscular Variability.
AB  - Purpose To demonstrate the reproducibility of the diffusion properties and three
      dimensional structural organization measurements of the lower leg muscles by
      using diffusion-tensor imaging (DTI) assessed with ultra-high-field-strength (7.0
      T) magnetic resonance (MR) imaging and tractography of skeletal muscle fibers. On
      the basis of robust statistical mapping analyses, this study also aimed at
      determining the sensitivity of the measurements to sex difference and
      intramuscular variability. Materials and Methods All examinations were performed
      with ethical review board approval; written informed consent was obtained from
      all volunteers. Reproducibility of diffusion tensor indexes assessment including
      eigenvalues, mean diffusivity, and fractional anisotropy (FA) as well as muscle
      volume and architecture (ie, fiber length and pennation angle) were characterized
      in lower leg muscles (n = 8). Intramuscular variability and sex differences were
      characterized in young healthy men and women (n = 10 in each group). Student t
      test, statistical parametric mapping, correlation coefficients (Spearman rho and
      Pearson product-moment) and coefficient of variation (CV) were used for
      statistical data analysis. Results High reproducibility of measurements (mean CV
      +/- standard deviation, 4.6% +/- 3.8) was determined in diffusion properties and
      architectural parameters. Significant sex differences were detected in FA (4.2%
      in women for the entire lower leg; P = .001) and muscle volume (21.7% in men for
      the entire lower leg; P = .008), whereas architecture parameters were almost
      identical across sex. Additional differences were found independently of sex in
      diffusion properties and architecture along several muscles of the lower leg.
      Conclusion The high-spatial-resolution DTI assessed with 7.0-T MR imaging allows
      a reproducible assessment of structural organization of superficial and deep
      muscles, giving indirect information on muscle function. (c)RSNA, 2018 Online
      supplemental material is available for this article.

PMID- 29381873
TI  - ASCIP Awardees List.

PMID- 29381874
TI  - Editors' Note.

PMID- 29381876
TI  - Recent and emerging reproductive biology research in Australia and New Zealand:
      highlights from the Society for Reproductive Biology Annual Meeting, 2017.
AB  - Research in reproductive science is essential to promote new developments in
      reproductive health and medicine, agriculture and conservation. The Society for
      Reproductive Biology (SRB) 2017 conference held in Perth (WA, Australia) provided
      a valuable update on current research programs in Australia and New Zealand. This
      conference review delivers a dedicated summary of significant questions, emerging
      concepts and innovative technologies presented in the symposia. This research
      demonstrates significant advances in the identification of precursors for a
      healthy pregnancy, birth and child, and discusses how these factors can influence
      disease risk. A key theme included preconception parental health and its effect
      on gametogenesis, embryo and fetal development and placental function. In
      addition, the perturbation of key developmental checkpoints was shown to
      contribute to a variety of pathological states that have the capacity to affect
      health and fertility. Importantly, the symposia discussed in this review
      emphasised the role of reproductive biology as a conduit for understanding the
      transmission of non-communicable diseases, such as metabolic disorders and
      cancers. The research presented at SRB 2017 has revealed key findings that have
      the prospect to change not only the fertility of the present generation, but also
      the health and reproductive capacity of future generations.

PMID- 29381877
TI  - How I do colonoscopy.

PMID- 29381878
TI  - Purpura fulminans - It's Not Always Sepsis.

PMID- 29381879
TI  - Long-Term Skeletal Outcomes of Primary Hyperparathyroidism Patients After
      Treatment with Parathyroidectomy: A Systematic Review and Meta-Analysis.
AB  - The aim of the study was to assess and define the association between
      parathyroidectomy (PTX) and long-term skeletal outcomes in primary
      hyperparathyroidism (PHPT) patients. PubMed, EMBASE, Web of Science, and Cochrane
      Central Register of Controlled Trials were systematically searched up to June 31,
      2017, without language restriction. Any study comparing skeletal outcomes
      [fracture risk or bone mineral density (BMD)] of PHPT patients after more than 12
      months of PTX treatment versus non-PTX treatment was included. Pooled relative
      risks or odds ratios with 95% confidence intervals and weighted mean difference
      were calculated using random-effects models irrespective of statistical
      heterogeneity assessed by I2 statistic. Finally, 5 randomized controlled trials
      (RCTs, n=584) and 10 cohort studies (CSs, n=12202) were included. CSs suggest PTX
      treatment versus non-PTX treatment is significantly associated with 36% reduction
      in the risk of fracture, with no heterogeneity, and an increase in the lumbar
      spine change by 0.55 WMD, with no heterogeneity. RCTs indicate PTX treatment
      versus non-PTX treatment is significantly associated with BMD change of 0.97 WMD
      at the lumbar spine with substantial heterogeneity, and 1.23 WMD at the femoral
      neck with no heterogeneity. The existing CSs indicate PTX-treatment versus non
      PTX-treatment might reduce the risk of fracture in PHPT patients. The existing
      RCTs do not provide sufficient or precise evidence that PTX-treatment affects the
      fracture risk of PHPT patients, but offer data that subsets of patients who could
      potentially benefit from PTX-treatment can be identified.

PMID- 29381880
TI  - Correction: Synergistic Effect of Free and Nano-encapsulated Chrysin-Curcumin on
      Inhibition of hTERT Gene Expression in SW480 Colorectal Cancer Cell Line.

PMID- 29381881
TI  - The Bronchus First and Vessels Simultaneously Stapled Technique: A Safe and
      Simple Method for Video-Assisted Right Upper Lobe Lobectomy.
AB  - OBJECTIVE:  Video-assisted thoracic surgery lobectomy is a minimally invasive
      procedure for major pulmonary resection. The purpose of this study was to present
      a novel approach with a thoracoscope in the right upper lobe and to compare
      different lobectomy methods at our institution. METHODS:  We reviewed the medical
      records of patients who underwent a thoracoscopic right upper lobectomy for lung
      cancer between September 2015 and September 2016. We performed 128 thoracoscopic
      right upper lobectomies: group A (n = 50) was treated with the bronchus-first and
      vessels simultaneously stapled method and group B (n = 78) was treated with the
      conventional isolation-ligation method. Preoperative mediastinal staging and
      lymphadenectomy followed the National Comprehensive Cancer Network guidelines.
      The intra- and postoperative outcomes were recorded and statistically compared.
      RESULTS:  All patients underwent successful thoracoscopic right upper
      lobectomies. No significant differences in mean intraoperative blood loss,
      massive hemorrhage (>500 mL), and postoperative complications were observed
      between the two groups (p < 0.05). The mean operative time of group A was less
      than that of group B (110.80 +/- 34.74 versus 167.01 +/- 48.38 minutes, p =
      0.000). The mean duration of chest drainage in group A was 4.34 +/- 2.06 days,
      which was shorter than that of group B (5.85 +/- 3.13 days, p = 0.017). No
      significant differences were observed in the local recurrence and distant
      recurrence between the two groups during the postoperative follow-up.
      CONCLUSIONS:  Thoracoscopic right upper lobectomy with the lobectomy bronchus
      first and vessels simultaneously stapled method is a safe and efficient procedure
      that leads to better recovery.

PMID- 29381882
TI  - Surgical Accuracy of an Early Intervention Knee Implant Instrumentation System.
AB  - Accuracy of component and limb alignment are critical parameters for the long
      term success of unicompartmental knee implants. In this study, we performed a
      laboratory evaluation of an instrumentation system which was designed for an
      early intervention (EI) type of unicompartmental knee. The accuracy of fit was
      evaluated by implanting in 20 sawbones full leg models. The overall alignment of
      the limb was compared pre- and postoperatively. The accuracy of placement of each
      component on its bone was measured. The mean overall alignment angle in the
      frontal plane was within 1 degrees  of target with less than 1 degrees  standard
      deviation. The components were positioned in frontal and sagittal planes with
      maximum errors of 2 degrees . The angular accuracy was better than in studies
      reported in the literature for manual instruments, and almost approached the
      accuracy of computer-assisted systems. The position of the femoral component in
      the recess was within 1 mm in most cases but the sagittal flexion angle was
      variable with a standard deviation of 6 degrees . Evaluation of a surgical
      technique in this way was a valuable method for determining accuracy and for
      highlighting any deficiencies in the system which could then be corrected.

PMID- 29381883
TI  - Outcomes Following Low-Profile Mesh Plate Osteosynthesis of Patella Fractures.
AB  - Treatment of patella fractures is fraught with complications and historically
      poor functional outcomes. A fixation method that allows for early mobilization
      and decreases symptomatic hardware rates will improve knee range of motion,
      postoperative functional status, and reoperation rates. The purpose of this study
      was to evaluate the functional outcomes after locked plate osteosynthesis of
      patella fractures at a Level 1 trauma center. A retrospective case series was
      conducted of patients who underwent open reduction internal fixation (ORIF) of a
      patella fracture using a locked mesh plating technique coupled with
      neutralization of forces on the distal pole of the patella. Twelve patients were
      evaluated at a mean follow-up of 19 months (range, 6-30) with physical exam,
      functional outcomes, and radiographs. There were 9 women and 3 men with an
      average age of 66.1 years (range, 53-75). Radiographic bony union was achieved in
      all patients by 3-month follow-up. Visual Analog Pain Score averaged 1.7 (median,
      1.0; range, 0-8), the mean Knee Outcome Score - Activities of Daily Living Scale
      was 83.9 (median, 92.1; range, 45.7-100.0), the mean Short Form Musculoskeletal
      Function Assessment (SMFA) Function Index was 9.9 (median, 3.7; range, 0.7-41.2),
      and the mean SMFA Bother Index was 11.1 (median, 3.1; range, 0-62.5). The SF-36
      Physical Component Score mean was 48.4 +/- 8.5 and the SF-36 Mental Component
      Score mean was 54.1 +/- 9.6. No complications developed and there were no
      reoperations for nonunion, infection, or symptomatic hardware. This study
      demonstrates that locked plate osteosynthesis for operative patella fractures can
      reliably achieve bony union with potentially superior functional outcomes as
      compared with traditional methods. Further studies are needed to evaluate plate
      fixation for patella fractures, but early results are promising.

PMID- 29381884
TI  - Osteochondral Injuries of the Knee in Pediatric Patients.
AB  - Osteochondral injuries in pediatric patients may occur as a result of a traumatic
      injury or secondary to an osteochondritis dissecans (OCD) lesion. Lateral patella
      dislocation is a common traumatic cause of osteochondral injury that typically
      occurs at the medial facet of the patella or at the lateral aspect of the distal
      femur. Multiple theories have been proposed for the cause of an OCD lesion in the
      knee, including trauma or repetitive microtrauma, local vascular insufficiency,
      and family history. The most "classic" location for OCD lesions of the knee is
      the lateral aspect of the medial femoral condyle of the distal femur. Multiple
      treatment options are available for both traumatic osteochondral injuries and OCD
      lesions, with important determining factors of treatment being skeletal maturity
      of the patient, instability of the fragment, lesion location, and size of the
      lesion. Nonsurgical management is appropriate in some situations. Surgical
      options range from simple fragment excision to internal fixation of the fracture
      fragment to more complex cartilage restoration or replacement procedures. This
      special focus section will discuss the diagnosis and treatment options for
      traumatic osteochondral knee injuries, including the subset secondary to juvenile
      OCD lesions.

PMID- 29381885
TI  - Differential expression profiles of conserved Snail transcription factors in the
      mouse testis.
AB  - Snail transcription factors are key regulators of cellular transitions during
      embryonic development and tumorigenesis. The closely related SNAI1 and SNAI2
      proteins induce epithelial-mesenchymal transitions (EMTs), acting predominantly
      as transcriptional repressors, while the functions of SNAI3 are unknown. An
      initial examination of Snai2-deficient mice provided evidence of deficient
      spermatogenesis. To address the hypothesis that Snail proteins are important for
      male fertility, this study provides the first comprehensive cellular expression
      profiles of all three mammalian Snail genes in the post-natal mouse testis. To
      evaluate Snail transcript expression profiles, droplet digital (dd) PCR and in
      situ hybridization were employed. Snai1, 2 and 3 transcripts are readily detected
      at 7, 14, 28 days post-partum (dpp) and 7 weeks (adult). Unique cellular
      expression was demonstrated for each by in situ hybridization and
      immunohistochemistry using Western blot-validated antibodies. SNAI1 and SNAI2 are
      in the nucleus of the most mature germ cell types at post-natal ages 10, 15 and
      26. SNAI3 is only detected from 15 dpp onwards and is localized in the Sertoli
      cell cytoplasm. In the adult testis, Snai1 and Snai2 transcripts are detected in
      spermatogonia and spermatocytes, while Snai3 is in both germ and Sertoli cells.
      SNAI1 protein is evident in nuclei of spermatogonia, spermatocytes, round
      spermatids and elongated spermatids (Stages IX-XII). SNAI2 is present in the
      nuclei of spermatogonia and spermatocytes, with a faint signal detected in round
      spermatids. SNAI3 was detected only in Sertoli cell cytoplasm, as in juvenile
      testes. Additionally, colocalization of SNAI1 and SNAI2 with previously
      identified key binding partners, LSD1 and PRC2 complex components, provides
      strong evidence that these important functional interactions are conserved during
      spermatogenesis to control gene activity. These distinct expression profiles
      suggest that each Snail family member has unique functions during
      spermatogenesis.

PMID- 29381886
TI  - Tubulins in C. elegans.
AB  - The C. elegans tubulin family is composed of nine alpha-, six beta-, and one
      gamma-tubulin. Tubulins are highly conserved, functioning as alpha-beta
      heterodimers that assemble into microtubules. These cylindrical and ubiquitous
      components of the cytoskeleton are critical for nearly all cellular and
      developmental processes. C. elegans has provided a model for the study of
      microtubules in multiple settings including separation of chromosomes, cellular
      polarity, and neuronal sensation. Tubulins and microtubules interact with a long
      list of other cellular proteins that regulate tubulin homeostasis, modify
      microtubule dynamics, and control incorporation into or disassociation of higher
      order cellular structures such as spindles or ciliary axonemes. A collection of
      enzymes modifies tubulins, often at the variable carboxyl-terminal tail, adding
      another layer of regulation to microtubule structure and function. Genetic and
      cytological studies in C. elegans have revealed roles for tubulin and its
      associated proteins in numerous contexts from embryogenesis to adult behavior.

PMID- 29381887
TI  - Myotonia Congenita Can Be Mistaken as Paroxysmal Kinesigenic Dyskinesia.

PMID- 29381888
TI  - Validity and Reliability Study of the Korean Tinetti Mobility Test for
      Parkinson's Disease.
AB  - OBJECTIVE: Postural instability and gait disturbance are the cardinal symptoms
      associated with falling among patients with Parkinson's disease (PD). The Tinetti
      mobility test (TMT) is a well-established measurement tool used to predict falls
      among elderly people. However, the TMT has not been established or widely used
      among PD patients in Korea. The purpose of this study was to evaluate the
      reliability and validity of the Korean version of the TMT for PD patients.
      METHODS: Twenty-four patients diagnosed with PD were enrolled in this study. For
      the interrater reliability test, thirteen clinicians scored the TMT after
      watching a video clip. We also used the test-retest method to determine
      intrarater reliability. For concurrent validation, the unified Parkinson's
      disease rating scale, Hoehn and Yahr staging, Berg Balance Scale, Timed-Up and Go
      test, 10-m walk test, and gait analysis by three-dimensional motion capture were
      also used. We analyzed receiver operating characteristic curve to predict
      falling. RESULTS: The interrater reliability and intrarater reliability of the
      Korean Tinetti balance scale were 0.97 and 0.98, respectively. The interrater
      reliability and intra-rater reliability of the Korean Tinetti gait scale were
      0.94 and 0.96, respectively. The Korean TMT scores were significantly correlated
      with the other clinical scales and three-dimensional motion capture. The cutoff
      values for predicting falling were 14 points (balance subscale) and 10 points
      (gait subscale). CONCLUSION: We found that the Korean version of the TMT showed
      excellent validity and reliability for gait and balance and had high sensitivity
      and specificity for predicting falls among patients with PD.

PMID- 29381889
TI  - Alteration in the Local and Global Functional Connectivity of Resting State
      Networks in Parkinson's Disease.
AB  - OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder that mainly
      leads to the impairment of patients' motor function, as well as of cognition, as
      it progresses. This study tried to investigate the impact of PD on the resting
      state functional connectivity of the default mode network (DMN), as well as of
      the entire brain. METHODS: Sixty patients with PD were included and compared to
      60 matched normal control (NC) subjects. For the local connectivity analysis, the
      resting state fMRI data were analyzed by seed-based correlation analyses, and
      then a novel persistent homology analysis was implemented to examine the
      connectivity from a global perspective. RESULTS: The functional connectivity of
      the DMN was decreased in the PD group compared to the NC, with a stronger
      difference in the medial prefrontal cortex. Moreover, the results of the
      persistent homology analysis indicated that the PD group had a more locally
      connected and less globally connected network compared to the NC. CONCLUSION: Our
      findings suggest that the DMN is altered in PD, and persistent homology analysis,
      as a useful measure of the topological characteristics of the networks from a
      broader perspective, was able to identify changes in the large-scale functional
      organization of the patients' brain.

PMID- 29381891
TI  - Molecular and functional characterization of the adiponectin (AdipoQ) gene in
      goat skeletal muscle satellite cells.
AB  - Objective: It is commonly accepted that adiponectin binds to its two receptors to
      regulate fatty acid metabolism in adipocytes. To better understand their
      functions in the regulation of intramuscular adipogenesis in goats, we cloned the
      three genes (adiponectin [AdipoQ], adiponectin receptor 1 [AdipoR1], and AdipoR2)
      encoding these proteins and detected their mRNA distribution in different
      tissues. We also determined the role of AdipoQ in the adipogenic differentiation
      of goat skeletal muscle satellite cells (SMSCs). METHODS: SMSCs were isolated
      using 1 mg/mL Pronase E from the longissimus dorsi muscles of 3-day-old female
      Nanjiang brown goats. Adipogenic differentiation was induced in satellite cells
      by transferring the cells to Dulbecco&apos;s modified Eagle&apos;s medium
      supplemented with an isobutylmethylxanthine, dexamethasone and insulin cocktail.
      The pEGFP-N1-AD plasmid was transfected into SMSCs using Lipofectamine 2000.
      Expression of adiponectin in tissues and SMSCs was detected by quantitative
      polymerase chain reaction and immunocytochemical staining. RESULTS: The three
      genes were predominantly expressed in adipose and skeletal muscle tissues.
      According to fluorescence and immunocytochemical analyses, adiponectin protein
      expression was only observed in the cytoplasm, suggesting that adiponectin is
      localized to the cytoplasm of goat SMSCs. In SMSCs overexpressing the AdipoQ
      gene, adiponectin promoted SMSC differentiation into adipocytes and significantly
      (p<0.05) up-regulated expression of AdipoR2, acetyl-CoA carboxylase, fatty-acid
      synthase, and sterol regulatory element-binding protein-1, though expression of
      CCAAT/enhancer-binding protein-alpha, peroxisome proliferator-activated receptor
      gamma, and AdipoR1 did not change significantly. CONCLUSION: Adiponectin induced
      SMSC differentiation into adipocytes, indicating that adiponectin may promote
      intramuscular adipogenesis in goat SMSC.

PMID- 29381890
TI  - Tau Positron Emission Tomography Imaging in Degenerative Parkinsonisms.
AB  - In recent years, several radiotracers that selectively bind to pathological tau
      proteins have been developed. Evidence is emerging that binding patterns of in
      vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD)
      patients closely resemble the distribution patterns of known neurofibrillary
      tangle pathology, with the extent of tracer binding reflecting the clinical and
      pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has
      clearly revealed cortical tau burden with a distribution pattern distinct from AD
      and increased cortical binding within the LBD spectrum. In progressive
      supranuclear palsy, the globus pallidus and midbrain have shown increased binding
      most prominently. Tau PET patterns in patients with corticobasal syndrome are
      characterized by asymmetrical uptake in the motor cortex and underlying white
      matter, as well as in the basal ganglia. Even in the patients with multiple
      system atrophy, which is basically a synucleinopathy, 18F-flortaucipir, a widely
      used tau PET tracer, also binds to the atrophic posterior putamen, possibly due
      to off-target binding. These distinct patterns of tau-selective radiotracer
      binding in the various degenerative parkinsonisms suggest its utility as a
      potential imaging biomarker for the differential diagnosis of parkinsonisms.

PMID- 29381892
TI  - Methodology effects on determining the energy concentration and the apparent
      total tract digestibility of components in diets fed to growing pigs.
AB  - Objective: An experiment was conducted to investigate the effects of different
      diet formulations: F1 (Two complicated basal diets containing different crude
      protein levels plus tested feedstuff) vs F2 (A simple corn soybean meal [SBM]
      basal diet plus tested feedstuff) combined with total collection (TC) or chromic
      oxide (Cr2O3) marker or acid-insoluble ash (AIA) marker method, and freeze-dry or
      oven-dry (OD) technique on estimation of nutrient digestibility in diets fed to
      growing pigs. METHODS: In F1, twelve barrows were allocated to two 6*4 Youden
      Squares. The treatment diets included a high protein basal (HPB) diet, a low
      protein basal (LPB) diet, a corn diet and a wheat bran (WB) diet formulated based
      on the HPB diet, and a SBM diet and a rapeseed meal (RSM) diet formulated based
      on the LPB diet. In F2, eight barrows were allocated to two 4*4 Latin Squares.
      The treatment diets included a corn basal diet, a SBM basal diet formulated based
      on the corn diet, and a WB diet and a RSM diet formulated based on the SBM diet.
      RESULTS: Concentration of digestible (DE) and metabolizable energy (ME), and the
      apparent total tract digestibility of gross energy, ash, neutral detergent fibre,
      and acid detergent fibre determined by Cr2O3 marker method were greater than
      those determined by TC and AIA marker methods in HPB, LPB, and RSM diets
      formulated by F1 and in corn diet formulated by F2 (p<0.05). The DE values in WB
      and both DE and ME values in SBM and RSM estimated using F1 were greater than
      those estimated using F2 (p<0.05). CONCLUSION: From the accuracy aspect, the AIA
      marker or TC method combined with OD technique is recommended for determining the
      energy concentration and nutrient digestibility of components in diets fed to
      growing pigs.

PMID- 29381893
TI  - Effects of dietary fiber levels on cecal microbiota composition in geese.
AB  - Objective: This study shows the effects of dietary fiber levels on cecal
      microbiota composition in geese at day 70 according to pyrosequencing of the 16S
      ribosomal RNA gene. METHODS: A total of 468 1-day-old healthy male Yangzhou
      goslings with similar body weight were randomly divided into 3 groups with 6
      replicates per group and 26 geese per replicate. Geese were fed diets with fiber
      levels of 2.5% (low fiber level diet, Group I) and 6.1% (Group III) during days 1
      70, respectively, or 4.3% for days 1-28 and 6.1% for days 29-70 (Group II).
      RESULTS: Low fiber level diet decreased body weight, average daily gain during,
      increased lower feed conversation rate of geese during day 1 to 70 (p<0.05). Low
      fiber level diet decreased the total operational taxonomic units, Chao1 index and
      Shannon index, whereas increased the Simpson index of cecal microbiota in geese
      at day 70. Low fiber level diet decreased the relative abundance of
      Bacteroidetes, Firmicutes, Bacteroides, and Paraprevotella in cecum of geese at
      day 70. The similarity of cecal microbiota between low fiber level diet group and
      other groups was smaller. CONCLUSION: This study indicates that the low fiber
      level diet decreased diversity of microbiota, and relative abundance of some
      beneficial microbiota in cecum of geese at day 70, implying that the low fiber
      level diet has negative influence on performance by altering the diversity and
      population of cecal microbiota in geese.

PMID- 29381894
TI  - Effect of Broussonetia papyrifera L. (paper mulberry) silage on dry matter
      intake, milk composition, antioxidant capacity and milk fatty acid profile in
      dairy cows.
AB  - Objective: This study was carried out to investigate the possible application of
      Broussonetia papyrifera (B. papyrifera) silage as a functional feeding stuff in
      dairy cattle. METHODS: Seventy-two Holstein cows were divided into four groups
      randomly and allocated to 6 pens with 3 individuals in each group and fed the
      original total mixed ratio (TMR) in the dairy farm or the new TMR with 5%, 10%,
      and 15% B. papyrifera silage, separately. Feed intake were recorded, milk and
      blood samples were collected, and milk composition, blood metabolites and milk
      fatty acids composition were measure at the end of the experiment. RESULTS: Dry
      matter intake of cows decreased when they fed on diet with B. papyrifera, but no
      differences were observed in body condition score, milk yield, milk protein and
      lactose, feed efficiency and serum metabolites between groups. Both 10% or 15% of
      B. papyrifera silage in the diet significantly increased the immunoglobulin A
      (IgA) and IgG in serum, 15% of B. papyrifera silage increased the content of
      serum catalase, superoxide dismutase, total antioxidant capacity, and decreased
      the content of 8-hydroxy-2'-deoxyguanosine. Furthermore, 10% or 15% of B.
      papyrifera silage resulted in a significant decrease in the milk somatic cell
      count, and increased the polyunsaturated fatty acids content in the milk.
      CONCLUSION: The diets with 10% to 15% of B. papyrifera silage might enhance the
      immune and antioxidant function of dairy cows and increase the polyunstaturated
      fatty acid concentration in the milk.

PMID- 29381895
TI  - Effect of inoculants and storage temperature on the microbial, chemical and
      mycotoxin composition of corn silage.
AB  - OBJECTIVE: To evaluate the effect of lactic acid bacteria and storage temperature
      on the microbial, chemical and mycotoxin composition of corn silage. METHODS:
      Corn was harvested at 32.8% dry matter, and chopped to 1 to 2 cm. The chopped
      material was subjected to three treatments: i) control (distilled water); ii)
      1*106 colony forming units (cfu)/g of Lactobacillus plantarum; iii) 1*106 cfu/g
      of Pediococcus pentosaceus. Treatments in triplicate were ensiled for 55 d at 20
      degrees C, 28 degrees C, and 37 degrees C in 1-L polythene jars following packing
      to a density of approximately 800 kg/m3 of fresh matter, respectively. At silo
      opening, microbial populations, fermentation characteristics, nutritive value and
      mycotoxins of corn silage were determined. RESULTS: L. plantarum significantly
      increased yeast number, water soluble carbohydrates, nitrate and deoxynivalenol
      content, and significantly decreased the ammonia N value in corn silage compared
      with the control (p<0.05). P. pentosaceus significantly increased lactic acid
      bacteria and yeast number and content of deoxynivalenol, nivalenol, T-2 toxin and
      zearalenone, while decreasing mold population and content of nitrate and 3-acetyl
      deoxynivalneol in corn silage when stored at 20 degrees C compared to the control
      (p<0.05). Storage temperature had a significant effect on deoxynivalenol,
      nivalenol, ochratoxin A, and zearalenone level in corn silage (p<0.05).
      CONCLUSION: Lactobacillus plantarum and Pediococcus pentosaceus did not decrease
      the contents of mycotoxins or nitrate in corn silage stored at three
      temperatures.

PMID- 29381896
TI  - Effects of dietary spermine supplementation on cell cycle, apoptosis, and amino
      acid transporters of the thymus and spleen in piglets.
AB  - Objective: This study investigated whether spermine supplementation could
      regulate cell cycle, apoptosis, and amino acid transporter-related genes
      expression in the thymus and spleen of early weaned piglets. METHODS: Eighty
      female piglets were randomly distributed to receive adequate nutrients
      supplemented with spermine (0.4 mmol/kg body weight/24 h) or to be provided with
      restricted nourishment supplemented with normal saline for 7 h or 3, 6, or 9 d in
      pairs. RESULTS: Regardless of administration time, spermine supplementation
      significantly up-regulated cyclin A2 gene expression but down-regulated p21 and
      cyclin D3 mRNA levels in the thymus and spleen and reduced cyclin E2 gene
      expression in the thymus of piglets (p< 0.05). Irrespective of the treatment
      period, the reduced Bax and caspase-3 gene expressions and improved Bcl-2 mRNA
      level were observed in the thymus and spleen of spermine-administrated piglets
      (p<0.05). Regardless of supplementation time, spermine intake significantly
      enhanced the expressions of amino acid transporter-related genes (SLC1A1, SLC1A5,
      SLC7A1, SLC7A7, and SLC15A1) in both thymus and spleen, as well as SLC7A9 in the
      spleen of piglets (p<0.05). In addition, extended spermine administration also
      markedly promoted cell proliferation, depressed apoptosis and modulated amino
      acid transport (p< 0.05), and such effects were the greatest during prolonged
      spermine supplementation (6 d) compared to the other time periods (p<0.05).
      CONCLUSION: Spermine supplementation may regulate cell cycle during the G1/S
      phase, suppress apoptosis and modulate amino acid transport. A period of 6 d of
      spermine supplementation is required to produce the optimal effects on
      nutritional implications.

PMID- 29381897
TI  - Effects of dietary beta-mannanase supplementation on the additivity of true
      metabolizable energy values for broiler diets.
AB  - OBJECTIVE: This experiment was conducted to determine the effects of dietary beta
      mannanase on the additivity of true metabolizable energy (TME) and nitrogen
      corrected true metabolizable energy (TMEn) for broiler diets. METHODS: A total of
      144 21-day-old broilers were randomly allotted to 12 dietary treatments with 6
      replicates. Five treatments consisted of 5 ingredients of corn, wheat, soybean
      meal, corn distillers dried grains with solubles, or corn gluten meal. One mixed
      diet containing 200 g/kg of those 5 ingredients also was prepared. Additional 6
      treatments were prepared by mixing 0.5 g/kg dietary beta-mannanase with those 5
      ingredients and the mixed diet. Based on a precision-fed chicken assay, TME and
      TMEn values for 5 ingredients and the mixed diet as affected by dietary beta
      mannanase were determined. RESULTS: Results indicated that when beta-mannanase
      was not added to the diet, measured TME and TMEn values for the diet did not
      differ from the predicted values for the diet, which validated the additivity.
      However, for the diet containing beta-mannanase, measured TMEn value was greater
      (p<0.05) than predicted TMEn value, indicating that the additivity was not
      validated. CONCLUSION: In conclusion, the additivity of energy values for the
      mixed diet may not be guaranteed if the diet contains beta-mannanase.

PMID- 29381898
TI  - Effect of natural pre-converted nitrite sources on color development in raw and
      cooked pork sausage.
AB  - Objective: The effect of pre-converted nitrites from natural sources (spinach,
      lettuce, celery, and red beet) on color development in raw and cooked pork
      sausage was investigated in this study. METHODS: The pork sausage was
      manufactured with six treatments: NC (negative control, nitrite free), PC
      (positive control, 150 ppm sodium nitrite), FS (3.0% fermented spinach extracts),
      FL (3.0% fermented lettuce extracts), FC (3.0% fermented celery extracts), and FR
      (3.0% fermented red beet extracts). RESULTS: The pH value of the pre-converted
      nitrites groups was lower than those treated with 150 ppm sodium nitrite
      (p<0.05). The color values of raw and cooked pork sausage added with pre
      converted nitrite showed slightly lower and/or similar lightness, lower redness,
      and higher yellowness values than PC. Color development (redness values) of
      cooked samples added with FS was higher than those of the NC and other treatments
      (FL, FC, and FR). Additionally, treatments with FS and FL were most effective for
      reducing thiobarbituric acid reactive substances and volatile basic nitrogen than
      the NC. CONCLUSION: Effects of natural nitrites from fermented vegetables on
      shelf stability of raw and cooked pork sausages were investigated. Fermented
      spinach extract was much more useful for maintaining the color development, but
      also inhibiting lipid and protein oxidation of cooked pork sausage. Therefore,
      pre-converted nitrite from spinach as a natural nitrite could be used as another
      natural nitrite source for making processed meat products.

PMID- 29381899
TI  - Identification of quantitative trait loci for the fatty acid composition in
      Korean native chicken.
AB  - Objective: Fatty acid composition is one of the most important meat quality
      traits because it can contribute to functional, sensorial, and nutritional
      factors. In this study, quantitative trait locus (QTL) analyses for fatty acid
      composition traits were investigated in thigh and breast meat of Korean native
      chicken (KNC). METHODS: In total, 18 fatty acid composition traits were
      investigated from each meat sample using 83 parents, and 595 F1 chicks of 20 week
      old. Genotype assessment was performed using 171 informative DNA markers on 26
      autosomes. The KNC linkage map was constructed by CRI-MAP software, which
      calculated genetic distances, with map orders between markers. The half-sib and
      full-sib QTL analyses were performed using GridQTL and SOLAR programs,
      respectively. RESULTS: In total, 30 QTLs (12 in the thigh and 18 in the breast
      meat) were detected by the half-sib analysis and 7 QTLs (3 in the thigh and 4 in
      the breast meat) were identified by the full-sib analysis. CONCLUSION: With
      further verification of the QTL regions using additional markers and positional
      candidate gene studies, these results can provide valuable information for
      determining causative mutations affecting the fatty acid composition of KNC meat.
      Moreover, these findings may aid in the selection of birds with favorable fatty
      acid composition traits.

PMID- 29381900
TI  - Effects of different dietary ratio of metabolizable glucose and metabolizable
      protein on growth performance, rumen fermentation, blood biochemical indices and
      ruminal microbiota of 8 to 10-month-old dairy heifers.
AB  - Objective: The aim of this experiment was to evaluate the effects of different
      dietary ratio of metabolizable glucose (MG) to metabolizable protein (MP) on
      growth performance, blood metabolites, rumen fermentation parameters and the
      ruminal microbial community of 8 to 10-month-old heifers. METHODS: A total of 24
      Holstein heifers weighing an average of 282.90 kg (8 month of age) were randomly
      assigned to four groups of six. The heifers were fed one of four diets of
      different dietary MG/MP (0.97, 1.07, 1.13, and 1.26). RESULTS: The results showed
      that the ratio of MG/MP affected the growth performance, blood metabolites, rumen
      fermentation parameters and the ruminal microbial community of heifers. The
      average daily gain of heifers was enhanced by increasing the ratio of MG/MP
      (p<0.05). The concentration of blood urea nitrogen, cholesterol, and low density
      lipoprotein cholesterol as well as the concentration of total volatile fatty acid
      in the rumen fluid of heifers decreased with the improvement in the ratio of
      dietary MG/MP (p<0.05). However, the relative amount of Ruminococcus albus and
      Butyrivibrio fibrisolvens in the rumen of heifers was increased significantly
      (p<0.05) when the dietary MG/MP increased. At the same time, with the improvement
      in dietary MG/MP, the amount of Fibrobacter succinogenes increased (p = 0.08).
      CONCLUSION: A diet with an optimal ratio (1.13) of MG/MP was beneficial for the
      improvement of growth, rumen fermentation, dietary protein and energy utilization
      of 8 to 10-month-old dairy heifers in this experiment.

PMID- 29381901
TI  - Dietary supplementation of finishing pigs with the docosahexaenoic acid-rich
      microalgae, Aurantiochytrium limacinum: effects on performance, carcass
      characteristics and tissue fatty acid profile.
AB  - OBJECTIVE: The aim of this experiment was to evaluate the effect of dietary
      supplementation with the docosahexaenoic acid (DHA)-rich microalgae,
      Aurantiochytrium limacinum (AURA) on pig performance, carcass traits, and the
      fatty acid composition of pork Longissimus lumborum (LL) and backfat. METHODS: A
      total of 144 Pig Improvement Company (PIC)*Goland finishing pigs (72 females and
      72 castrated males) of mean weight 117.1 (+/-13.1) kg were blocked by sex and
      body weight and provided with 0% or 1% AURA in isonutritive and isocaloric diets.
      A total of 24 pens provided 12 replicates per treatment. Animals were weighed on
      day 0 and 28 with feed and water intake recorded per pen. After 31 days
      supplementation (28 days of study and 3 days until the slaughtering date) three
      animals per pen (n = 72) were slaughtered and the LL and backfat thickness, lean
      meat content and dressing percentage were recorded for the carcasses. The fatty
      acid (FA) profile of the LL and backfat was established by direct FA methyl ester
      synthesis. RESULTS: No differences were observed for any performance parameters
      or carcass traits. Supplementation with AURA resulted in significant changes to
      the FA profiles of both the LL and backfat with male and female pigs responding
      differently to supplementation in terms of particular FAs. Overall, pork LL
      samples had significantly higher eicosapentaenoic acid (p<0.001) and DHA
      concentrations (p<0.001), and higher omega-3 (n-3) FAs (p<0.001), as well as an
      increased omega3:omega6 (n-3:n-6) ratio (p = 0.001). For backfat, supplementation
      resulted in significantly higher amounts of DHA (p<0.001) and n-3 FAs (p<0.001).
      CONCLUSION: These results indicate that dietary supplementation with 1% AURA over
      a 31 day period can increase the FA composition of pork LL and backfat,
      specifically the DHA, with no major impact on growth performance and carcass
      traits.

PMID- 29381902
TI  - Additivity of values for phosphorus digestibility in corn, soybean meal, and
      canola meal in diets fed to growing pigs.
AB  - Objective: This study was conducted to determine the apparent and standardized
      total tract digestibility (ATTD and STTD) of phosphorus (P) in corn, soybean meal
      (SBM), and canola meal (CM), and additivity of values for ATTD and STTD of P in
      corn, SBM, and CM in diets fed to growing pigs. METHODS: Thirty-six growing
      barrows (initial body weight of 21.6+/-1.7 kg) were placed in metabolism crates
      and allotted to a completely randomized design with 6 diets and 6 pigs per diet.
      Six diets were formulated using corn, SBM or CM as the sole source of P, or corn
      and SBM, or corn and CM, or corn, SBM, and CM as the P source in each diet,
      respectively. Fecal samples were collected for 5 d following a 7 d adaptation
      period to the diets. RESULTS: Values for ATTD and STTD of P in corn, SBM, and CM
      in growing pigs were 33.12% and 37.76%, 50.19% and 56.62%, 34.93% and 39.45%,
      respectively. The ATTD and STTD of P in SBM were greater (p<0.05) than those in
      corn and CM. However, there were no differences in the ATTD or STTD of P between
      corn and CM. The determined STTD of P in the mixture of corn and SBM, corn and
      CM, and corn, SBM, and CM is not different from the calculated STTD values.
      CONCLUSION: Values for STTD of P in corn, SBM, and CM are additive in their
      mixture fed to growing pigs.

PMID- 29381903
TI  - A demonstration of the H3 trimethylation ChIP-seq analysis of galline follicular
      mesenchymal cells and male germ cells.
AB  - OBJECTIVE: Trimethylation of histone 3 (H3) at 4th lysine N-termini (H3K4me3) in
      gene promoter region was the universal marker of active genes specific to cell
      lineage. On the contrary, coexistence of trimethylation at 27th lysine (H3K27me3)
      in the same loci-the bivalent H3K4m3/H3K27me3 was known to suspend the gene
      transcription in germ cells, and could also be inherited to the developed stem
      cell. In galline species, throughout example of H3K4m3 and H3K27me3 ChIP-seq
      analysis was still not provided. We therefore designed and demonstrated such
      procedures using ChIP-seq and mRNA-seq data of chicken follicular mesenchymal
      cells and male germ cells. METHODS: Analytical workflow was designed and provided
      in this study. ChIP-seq and RNA-seq datasets of follicular mesenchymal cells and
      male germ cells were acquired and properly preprocessed. Peak calling by Model
      based analysis of ChIP-seq 2 was performed to identify H3K4m3 or H3K27me3
      enriched regions (Fold-change>=2, FDR<=0.01) in gene promoter regions.
      Integrative genomics viewer was utilized for cellular retinoic acid binding
      protein 1 (CRABP1), growth differentiation factor 10 (GDF10), and gremlin 1
      (GREM1) gene explorations. RESULTS: The acquired results indicated that
      follicular mesenchymal cells and germ cells shared several unique gene promoter
      regions enriched with H3K4me3 (5,704 peaks) and also unique regions of bivalent
      H3K4m3/H3K27me3 shared between all cell types and germ cells (1,909 peaks).
      Subsequent observation of follicular mesenchyme-specific genes-CRABP1, GDF10, and
      GREM1 correctly revealed vigorous transcriptions of these genes in follicular
      mesenchymal cells. As expected, bivalent H3K4m3/H3K27me3 pattern was manifested
      in gene promoter regions of germ cells, and thus suspended their transcriptions.
      CONCLUSION: According the results, an example of chicken H3K4m3/H3K27me3 ChIP-seq
      data analysis was successfully demonstrated in this study. Hopefully, the
      provided methodology should hereby be useful for galline ChIP-seq data analysis
      in the future.

PMID- 29381904
TI  - Genetic parameter estimation for milk beta-hydroxybutyrate and acetone in early
      lactation and its association with fat to protein ratio and energy balance in
      Korean Holstein cattle.
AB  - OBJECTIVE: The objective of this study was to estimate the genetic parameters for
      milk beta-hydroxybutyrate (BHBA), acetone (Ac), fat protein ratio (FPR), and
      energy balance (EB) using milk test day records and investigate the effect of
      early lactation FPR and EB on milk ketone body concentrations. METHODS: Total
      262,940 test-day records collected from Korea Animal Improvement Association
      during the period of 2012 to 2016 were used in this study. BHBA and Ac
      concentrations in milk were measured by Fourier transform infrared spectroscopy
      (FTIR). FPR values were obtained using test day records of fat and protein
      percentage. EB was calculated using previously developed equation based on
      parity, lactation week, and milk composition data. Genetic parameters were
      estimated by restricted maximum likelihood procedure based on repeatability model
      using Wombat program. RESULTS: Elevated milk BHBA and Ac concentrations were
      observed during the early lactation under the negative energy balance. Milk FPR
      tends to decrease with the decreasing ketone body concentrations. Heritability
      estimates for milk BHBA, Ac, EB, and FPR ranged from 0.09 to 0.14, 0.23 to 0.31,
      0.19 to 0.52, and 0.16 to 0.42 respectively at parity 1, 2, 3, and 4. The overall
      heritability for BHBA, Ac, EB and FPR were 0.29, 0.32, 0.58, and 0.38
      respectively. A common pattern was observed in heritability of EB and FPR along
      with parities. CONCLUSION: FPR and EB can be suggested as potential predictors
      for risk of hyperketonemia. The heritability estimates of milk BHBA, Ac, EB, and
      FPR indicate that the selective breeding may contribute to maintaining the milk
      ketone bodies at optimum level during early lactation.

PMID- 29381905
TI  - Genetic diversity analysis of Thai indigenous chickens based on complete
      sequences of mitochondrial DNA D-loop region.
AB  - OBJECTIVE: Complete mtDNA D-loop sequences of four Thai indigenous chicken
      varieties, including Pra-dhu-hang-dam (PD), Leung-hang-khao (LK), Chee (CH), and
      Dang (DA) were explored for genetic diversity and relationships with their
      potential ancestor and possible associates to address chicken domestication in
      Thailand. METHODS: A total of 220 complete mtDNA D-loop sequences of the four
      Thai indigenous chicken varieties were obtained by Sanger direct sequencing of
      polymerase chain reaction amplicons of 1,231 to 1,232 base pair in size. A
      neighbor-joining dendrogram was constructed with reference complete mtDNA D-loop
      sequences of Red Junglefowl (RJF) and those different chicken breeds available on
      National Center for Biotechnology Information database. Genetic diversity indices
      and neutrality test by Tajima's D test were performed. Genetic differences both
      within and among populations were estimated using analysis of molecular variance
      (AMOVA). Pairwise fixation index (FST) was conducted to evaluated genetic
      relationships between these varieties. RESULTS: Twenty-three identified
      haplotypes were classified in six haplogroups (A-E and H) with the majority
      clustered in haplogroup A and B. Each variety was in multiple haplogroups with
      haplogroups A, B, D, and E being shared by all studied varieties. The averaged
      haplotype and nucleotide diversities were, respectively 0.8607 and 0.00579 with
      non-significant Tajima's D values being observed in all populations. Haplogroup
      distribution was closely related to that of RJF particularly Gallus gallus gallus
      (G. g. gallus) and G. g. spadiceus. As denoted by AMOVA, the mean diversity was
      mostly due to within-population variation (90.53%) while between-population
      variation (9.47%) accounted for much less. By pairwise FST, LK was most closely
      related to DA (FST = 0.00879) while DA was farthest from CH (FST = 0.24882).
      CONCLUSION: All 4 Thai indigenous chickens are in close relationship with their
      potential ancestor, the RJF. A contribution of shared, multiple maternal lineages
      was in the nature of these varieties, which have been domesticated under neutral
      selection.

PMID- 29381906
TI  - Feeding Di-ammonium Phosphate as a Phosphorous Source in Finishing Lambs Reduced
      Excretion of Phosphorus in Feces without Detrimental Effects on Animal
      Performance.
AB  - Objective: Phosphorous (P) sources with greater bioavailability might increase
      animal production efficiency and decrease environmental pollution. The objective
      of current study was to determine animal performance, nutrient digestibility,
      blood metabolites and fecal P concentration in finishing lambs fed a diet with
      either di-calcium phosphate (DCP) or di-ammonium phosphate (DAP) as a P source.
      Methods: Twelve 4-month-old male lambs (initial body weight 24.87+/-3.4 kg) were
      randomly allocated to a diet with either DCP or DAP (~261 g/kg of total diet P)
      fed ad libitum for 93 days. Diets were iso-nitrogenous and iso-energetic and had
      same calcium (Ca) and P concentrations. Results: The DAP contained 19.7 g/kg of
      dry matter (DM) Ca, 185.4 g/kg DM P and 14623 ppm fluorine, while DCP contained
      230.3 g/kg DM Ca, 195.2 g/kg DM P and 1039 ppm fluorine. The diet with DAP
      contained 60 ppm fluorine while the diet with DCP contained 13 ppm fluorine.
      Lambs fed the diet with DAP tended to have a greater daily DM intake compared to
      those fed diet with DCP (P = 0.09). Lambs fed DAP had greater plasma P
      concentration and alkaline phosphatase activity (P <= 0.01) compared with lambs
      fed DCP. Dry matter and organic matter digestibility of the diets were similar
      between two treatments at days 60 and 90, while they were greater in lambs fed
      DCP (P < 0.05) at day 30 of the trial. Feeding DAP increased P digestibility
      (58.7 vs. 50.2 %; P < 0.05) and decreased fecal P concentration in lambs compared
      with feeding DCP (3.1 vs. 3.8 g/kg DM; P < 0.05). Conclusion: Providing ~261 g/kg
      of total diet P as DAP in the diet of finishing lambs improved the
      bioavailability of P in the body and decreased excretion of P in feces without
      affecting lamb performance.

PMID- 29381907
TI  - Comparison of microbial communities in swine manure at various temperatures and
      storage times.
AB  - Objective: This study was designed to investigate the effects of temperature and
      storage time on the evolution of bacterial communities in swine manure. METHODS:
      Manure was stored at -20 degrees C, 4 degrees C, 20 degrees C, or 37 degrees C
      and sampled at 7-day intervals over 28 days of storage, for a total of 5 time
      points. To assess the bacterial species present, 16S ribosomal RNA gene sequences
      were analyzed using pyrosequencing. RESULTS: After normalization, 113,934
      sequence reads were obtained, with an average length of 466.6+/-4.4 bp. The
      diversity indices of the communities reduced as temperature and storage time
      increased, and the slopes of rarefaction curves decreased from the second week in
      samples stored at -20 degrees C and 4 degrees C. These results indicate that the
      richness of the bacterial community in the manure reduced as temperature and
      storage time increased. Firmicutes were the dominant phylum in all samples
      examined, ranging from 89.3% to 98.8% of total reads, followed by Actinobacteria,
      which accounted for 0.6% to 7.9%. A change in community composition was observed
      in samples stored at 37 degrees C during the first 7 days, indicating that
      temperature plays an important role in determining the microbiota of swine
      manure. Clostridium, Turicibacter, Streptococcus, and Lactobacillus within
      Firmicutes, and Corynebacterium within Actinobacteria were the most dominant
      genera in fresh manure and all stored samples. CONCLUSION: Based on our findings,
      we propose Clostridium as an indicator genus of swine manure decomposition in an
      anaerobic environment. The proportions of dominant genera changed in samples
      stored at 20 degrees C and 37 degrees C during the fourth week. Based on these
      results, it was concluded that the microbial communities of swine manure change
      rapidly as storage time and temperature increase.

PMID- 29381908
TI  - Long-term changes in computed tomography and ultrasound utilization in a
      pediatric emergency department.
AB  - OBJECTIVE: Many studies have proposed reducing unnecessary use of computed
      tomography (CT), and ongoing studies in pediatric populations are aiming to
      decrease radiation dosages whenever possible. We aimed to evaluate the long-term
      changes in the utilization patterns of CT and ultrasound (US) in pediatric
      emergency departments (PEDs). METHODS: This retrospective study reviewed the
      electronic medical data of patients who underwent CT and/or US in the PED of a
      tertiary referral hospital from 2000 to 2014. We compared the changes in
      utilization patterns of brain and abdominal CT scans in pediatric patients and
      analyzed changes in abdominal US utilization in the PED. RESULTS: During the
      study period, 196,371 patients visited the PED. A total of 12,996 brain and
      abdominal CT scans and 12,424 abdominal US were performed in the PED. Comparison
      of CT use in pediatric patients before and after 2007 showed statistically
      decreasing trends after 2007, expressed as the coefficient values of the
      differences in groups. The numbers of brain and abdominal CT scans showed a
      significant decreasing trend in children, except for abdominal CT in adolescents.
      The abdominal US/CT ratio in the PED showed a statistically significant increase
      (2.68; 95% confidence interval, 1.87 to 3.49) except for the adolescent group
      (5.82; 95% confidence interval, -2.06 to 13.69). CONCLUSION: Overall, CT use in
      pediatric patients has decreased since 2007. Pediatric US use has also shown a
      decreasing trend; however, the abdominal US/CT ratio in pediatric patients showed
      an increasing trend, except for adolescents.

PMID- 29381909
TI  - Metoprolol treatment of dual cocaine and bupropion cardiovascular and central
      nervous system toxicity.
AB  - Cardiovascular and central nervous system (CNS) toxicity, including
      tachydysrhythmia, agitation, and seizures, may arise from cocaine or bupropion
      use. We report acute toxicity from the concomitant use of cocaine and bupropion
      in a 25-year-old female. She arrived agitated and uncooperative, with a history
      of possible antecedent cocaine use. Her electrocardiogram demonstrated
      tachycardia at 130 beats/min, with a corrected QT interval of 579 ms. Two doses
      of 5 mg intravenous metoprolol were administered, which resolved the agitation,
      tachydysrhythmia, and corrected QT interval prolongation. Her comprehensive
      toxicology screen returned positive for both cocaine and bupropion. We believe
      clinicians should be aware of the potential for synergistic cardiovascular and
      CNS toxicity from concomitant cocaine and bupropion use. Metoprolol may represent
      an effective initial treatment. Unlike benzodiazepines, metoprolol directly
      counters the pharmacologic effects of stimulants without respiratory depression,
      sedation, or paradoxical agitation. A lipophilic beta-blocker, metoprolol has
      good penetration of the CNS and can counter stimulant-induced agitation.

PMID- 29381910
TI  - Somatic KRAS mutation in an infant with linear nevus sebaceous syndrome
      associated with lymphatic malformations: A case report and literature review.
AB  - RATIONALE: Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous
      syndrome, characterized by nevus sebaceous,central nervous system (CNS), ocular
      and skeletal abnormalities. The present study describes KRAS somatic mosaic
      mutation in a case of LNSS with lymphatic malformations (LMs). PATIENT CONCERNS:
      A 4-month-old female with a clinical diagnosis of LNSS presented with infantile
      spasms, mental retardation, skull dysplasia, ocular abnormalities, congenital
      atrial septal defect, and LMs. DIAGNOSIS: Cervical ultrasonography revealed a 4.6
      * 4.6 * 2.2cm no echo packet with clear boundary in the subcutaneous tissues of
      the right neck. The neck MRI indicated a cyst in the subcutaneous tissues of the
      right neck. Whole-exome sequencing revealed a low-level heterozygous mutation of
      the KRAS gene (c.35C > T; p.G12D, 19%) in the skin lesion sample. This mutation
      was not present in the blood samples of the patient and her parents.
      INTERVENTIONS: The patient received sclerotherapy with paicibanil (OK-432)
      injection for the cyst. OUTCOMES: Following 1 year of treatment, the patient
      exhibited fewer seizures. The mental and motor development was significantly
      improved. The patient can currently walk with assistance and speak simple words.
      LESSONS: LNSS is a rare, congenital neurocutaneous syndrome consisting of a
      spectrum of abnormalities involving the skin, central nervous system, eyes, LMs
      and other systems. LNSS can be caused by postzygotic somatic mutation in the RAS
      family of genes. Multidisciplinary evaluation and treatment is needed.

PMID- 29381911
TI  - Risk of macular degeneration affected by polymorphisms in Matrix
      metalloproteinase-2: A case-control study in Chinese Han population.
AB  - The purpose of this study was to investigate the correlation of single nucleotide
      polymorphisms (SNPs) in Matrix metalloproteinase -2 (MMP-2) gene and the risk of
      age-related macular degeneration (AMD) in Chinese Han population.A total of 126
      AMD patients and 141 healthy controls participated in this study. Genotypes of
      MMP-2 gene polymorphisms were identified by the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). chitest was used to detect
      the differences of genotypes and alleles frequencies between case and control
      groups. Relative risk of AMD was evaluated by odds ratios (ORs) with 95%
      confidence intervals (CIs).Distribution of variant allele carriers (computed
      tomography + TT genotypes) of MMP-2 gene rs243865 SNP was significantly different
      between case and control groups, and might act as protective factors for the
      onset of AMD (P = .044, OR = 0.583, 95% CI = 0.344-0.987). Nevertheless, the T
      allele might reduce the AMD risk (P = .030, OR = 0.611, 95% CI = 0.390-0.956).
      However, no significant association existed between rs243865 and AMD risk in the
      subgroup analysis based on age. GA + AA genotypes of rs243866 SNP may associate
      with a decreased risk of AMD in the age<=65 years subgroup (P = .028, OR = 0.399,
      95% CI = 0.174-0.915).MMP-2 gene rs243865 and rs243866 SNPs associated with the
      risk of AMD. Further studies should be performed to confirm the results.

PMID- 29381912
TI  - Association of diabetes mellitus with thyroid cancer risk: A meta-analysis of
      cohort studies.
AB  - BACKGROUND: Diabetes mellitus (DM) is inconsistently associated with thyroid
      cancer risk. The purpose of this study was to summarize findings from cohort
      studies regarding the strength of the association of DM with subsequent thyroid
      cancer risk. METHODS: Electronic searches were performed in PubMed, EmBase, and
      the Cochrane Library to identify studies from inception to July 2016. Cohort
      studies reporting risk estimates with 95% confidence intervals (CIs) of thyroid
      cancer in DM and non-DM patients were included. A random-effects meta-analysis
      was performed to the risk of thyroid cancer in DM compared with non-DM
      participants. RESULTS: Sixteen cohort studies were included, with a total of
      10,725,884 individuals. These studies reported a total of 8032 cases of thyroid
      cancer. Overall, DM was associated with an increased risk of thyroid cancer
      (relative risk [RR], 1.20; 95% CI, 1.09-1.33; P < .001). Further, there was no
      significant difference was found between DM and non-DM for the risk of thyroid
      cancer in men (RR, 1.14; 95% CI, 1.00-1.30; P = .057), while a significant
      correlation was found in a pooled analysis in women (RR, 1.11; 95% CI, 1.06-1.17;
      P < .001). Finally, subgroup analyses suggested that country and mean age might
      correlate with the relationship between DM and the risk of thyroid cancer.
      CONCLUSION: This study suggested that patients with DM have significantly
      increased risk of thyroid cancer compared nondiabetics. This positive association
      was prominent in women, and not significant in men. Further large-scale studies
      are required to verify the nature of the association, which should be evaluated
      in specific subpopulations.

PMID- 29381913
TI  - The hypospadias classification affected the surgical outcomes of staged oral
      mucosa graft urethroplasty in hypospadias reoperation: An observational study.
AB  - The staged graft urethroplasty is a recommended technique for repairing complex
      hypospadias. This retrospective study aimed to investigate the outcomes of this
      technique in hypospadias patients undergoing reoperation and to analyze the
      underlying contributing factors including age, meatus location, and graft and
      suture type.We retrospectively analyzed 40 hypospadias patients undergoing
      reoperation who received a staged oral graft urethroplasty, including 15 buccal
      mucosal grafts and 25 lingual mucosal grafts. Median age at presentation was 18.5
      years, and median follow-up was 17.5 months (range 8-30 months). The patients
      were classified according to their original meatus location.Twenty-five
      complications developed in 12 of 40 (30%) cases, including 6 fistulas (15%), 7
      infections (17.5%), 9 cases of glans dehiscence (22.5%), and 3 cases of stenosis
      (7.5%). There was no significant difference in the overall complication rates
      between prepuberty and postpuberty groups. In addition, no significant difference
      in complications was found between the 2 graft techniques. The complications were
      significantly higher in the original perineal type compared with the original
      penoscrotal type (7/10 vs 5/30, P = .0031). Seven patients who originally had
      perineal hypospadias developed multiple complications.Based on this study, the
      staged graft urethroplasty is an effective technique in reoperative hypospadias
      repairs with reasonable complication risk. The hypospadias classification affects
      the surgical outcomes.

PMID- 29381914
TI  - Preoperative bathing with chlorhexidine reduces the incidence of surgical site
      infections after total knee arthroplasty: A meta-analysis.
AB  - BACKGROUND: Surgical site infection is a devastating postoperative complication,
      and the occurrence ranges from 1% to 2% after total knee arthroplasty (TKA). The
      efficacy of the preoperative use of chlorhexidine for reducing infection has been
      debated. This meta-analysis aimed to examine the efficacy of the use of
      chlorhexidine to prevent surgical site infections after TKA. METHODS: In February
      2017, a systematic literature review was conducted using the following electronic
      databases: PubMed, EMBASE, Web of Science, Cochrane Database of Systematic
      Reviews, and the Google database. Data from randomized controlled trials (RCTs)
      and retrospective comparative study (RCS) that compared the use of chlorhexidine
      versus control washes to prep patients for TKA were retrieved. The primary
      endpoint was to compare the total incidence of infection with and without the use
      of chlorhexidine. The secondary outcomes were the incidence of infection in low
      risk category patients, moderate-risk category patients, and high-risk category
      patients. After testing for publication bias and heterogeneity between studies,
      data were aggregated for random-effects modeling when necessary. RESULTS: Four
      clinical trials that included 8787 patients (chlorhexidine group: n = 2615,
      control group: n = 6172) were ultimately included in the meta-analysis.
      Chlorhexidine was associated with a reduced total incidence of infection,
      corresponding to a reduction of 1.69% [risk ratio (RR) = 0.22; 95% confidence
      interval (95% CI) = 0.12-0.40; P = .000]. Similarly, chlorhexidine was associated
      with a reduction in the incidence of infection among patients in the moderate
      risk category (RR, 0.18; 95% CI, 0.05-0.63; P = .007) and the high-risk category
      (RR, 0.13; 95% CI, 0.03-0.67; P = .014). There was no significant difference
      between the incidence of infection in low-risk category patients with
      chlorhexidine use compared with the use of control washes (RR, 0.60; 95% CI, 0.22
      1.60; P = .330). CONCLUSION: The preoperative use of chlorhexidine could reduce
      the total incidence of infection and the incidence of infection in moderate-risk
      and high-risk category patients. The overall evidence and the number of included
      studies was limited; thus, a greater number of high-quality RCTs is still needed
      to further identify the effects of chlorhexidine on reducing the incidence of
      infection after TKA.

PMID- 29381915
TI  - Biomarkers identification for acute myocardial infarction detection via weighted
      gene co-expression network analysis.
AB  - The study aimed to seek potential biomarkers for acute myocardial infarction
      (AMI) detection and treatment.The dataset GSE48060 was used, consisting of 52
      peripheral blood samples (31 AMI samples and 21 normal controls). By limma
      package, differentially expressed genes (DEGs) between 2 kinds of samples were
      identified, followed by enrichment analysis, subpathway analysis, protein-protein
      interaction (PPI) network analysis, and transcription factor network (TFN)
      analysis. Weighted gene co-expression network analysis was used to further
      extract key modules relating to AMI, followed by enrichment and TFN analyses.
      Expression validation was performed via meta-analysis of 2 datasets, GSE22229 and
      GSE29111.A set of 428 DEGs in AMI were screened out, and the upregulated toll
      like receptor (TLR) family genes (TLR1, TLR2, and TLR10) were enriched in wound
      response, immune response and inflammatory response functions, and downregulated
      genes (GBP5, CXCL5, GZMA, CCL5, and CCL4) were correlated with immune response.
      CCL5, GZMA, GZMB, TLR2, and formyl peptide receptor 1 (FPR1) were predicted as
      crucial nodes in the PPI network. Signal transducer and activator of
      transcription 1 (STAT1) was the key transcription factor (TF) with multiple
      targets. The grey module was highly related to AMI. Genes in this module were
      closely related to regulation of macrophage activation, and spermatogenic leucine
      zipper 1 (SPZ1) was identified as a TF. Expressions of TLR2 and FPR1 were
      confirmed via the integrated matrix.Several potential biomarkers for AMI
      detection were identified, such as GZMB, GBP5, FPR1, TLR2, STAT1, and SPZ1. They
      might exert their functions via regulation of immune and inflammation responses.
      Genes in grey module play significant roles in AMI via regulation of macrophage
      activation.

PMID- 29381916
TI  - Blood culture-negative endocarditis: Improving the diagnostic yield using new
      diagnostic tools.
AB  - Blood culture-negative endocarditis (BCNE) may represent up to 70% of all
      endocarditis cases, depending on series. From 2001 to 2009, we implemented in our
      laboratory a multimodal diagnostic strategy for BCNE that included systematized
      testing of blood, and when available, valvular biopsy specimens using
      serological, broad range molecular, and histopathological assays. A causative
      microorganism was identified in 62.7% of patients.In this study from January 2010
      to December 2015, in an effort to increase the number of identified causative
      microorganisms, we prospectively added to our diagnostic protocol specific real
      time (RT) polymerase chain reaction (PCR) assays targeting various endocarditis
      agents, and applied them to all patients with BCNE admitted to the 4 public
      hospitals in Marseille, France.A total of 283 patients with BCNE were included in
      the study. Of these, 177 were classified as having definite endocarditis. Using
      our new multimodal diagnostic strategy, we identified an etiology in 138 patients
      (78.0% of cases). Of these, 3 were not infective (2.2%) and 1 was diagnosed as
      having Mycobacterium bovis BCG endocarditis. By adding specific PCR assays from
      blood and valvular biopsies, which exhibited a significantly greater sensitivity
      (P < 10) than other methods, causative agents, mostly enterococci, streptococci,
      and zoonotic microorganisms, were identified in an additional 27 patients (14
      from valves only, 11 from blood only, and 2 from both). Finally, in another 107
      patients, a pathogen was detected using serology in 37, valve culture in 8, broad
      spectrum PCR from valvular biopsies and blood in 19 and 2, respectively,
      immunohistochemistry from valves in 3, and a combination of several assays in
      38.By adding specific RT-PCR assays to our systematic PCR testing of patients
      with BCNE, we increased the diagnostic efficiency by 24.3%, mostly by detecting
      enterococci and streptococci that had not been detected by other diagnostic
      methods, but also agents requiring specific management such as Mycoplasma hominis
      and Tropheryma whipplei.

PMID- 29381917
TI  - Changes of cervical sagittal alignments during motions in patients with cervical
      kyphosis.
AB  - Changes of cervical sagittal alignment during motion in cervical kyphosis
      patients have never been published before. This study was to investigate the
      changes and provide a better reference for orthopedic treatment.Randomized double
      blind repeat trial was carried out on 60 patients with cervical kyphosis. On
      standard position, hyper flexion, and hyper extension sagittal radiographs, the
      following measurements were made: the C2-7 vertebral body spatial alignment angle
      (?A), C2-7 vertebral lower terminal lamina tilt angle (?B), C2/3 to C6/7
      segmental intervertebral space angle (?C), the distance from the posterior edge
      of odontoid to C7 vertebral body (D value), and the difference of angle A, B, and
      C between cervical flexion and extension movement. Another 60 healthy volunteers
      were enrolled, of whom the cervical curve apex was determined using Borden's
      method to compare change and distribution characteristics to patients with
      cervical kyphosis and C value.In standard lateral position, ?A was positive and
      increased from C2 to C7. In hyper extension position, ?A decreased with reducing
      amplitude from C2 to C7 compared with the standard position, whereas in hyper
      flexion position, the average value of ?A increased with decreasing amplitude
      from C2 to C7. ?B followed similar change regularities as ?A with a larger mean
      value. In cervical flexion and extension movement, ?A change of upper vertebral
      body (?D) was almost equal to ?A change of lower vertebral body and ?C change
      between the adjacent 2 vertebral bodies (?E). The curve apex distribution was
      almost between C4 and C5 in cervical kyphosis patients. A significant difference
      was observed between cervical kyphosis patients and normal people in C value and
      D value.The correction of the cervical kyphosis can be carried out from the apex
      of the cervical spine that provides a solid theoretical foundation for the
      correction of the cervical kyphosis.

PMID- 29381918
TI  - Diagnosis of tuberculous pleurisy with combination of adenosine deaminase and
      interferon-gamma immunospot assay in a tuberculosis-endemic population: A
      prospective cohort study.
AB  - The aim of this study was to identify the optimal cut-off value of T cell enzyme
      linked immunospot assay for tuberculosis (T-SPOT.TB) and evaluate its diagnostic
      performance alone (in the peripheral blood) or in combination with the adenosine
      deaminase (ADA) activity test (in peripheral blood and the pleural fluid) in
      patients with tuberculous pleurisy.Adult patients presenting with pleural
      effusion were included in this prospective cohort study. Tuberculous pleurisy was
      diagnosed by T-SPOT.TB in peripheral blood and a combination of T-SPOT.TB and ADA
      activity test in pleural fluid and peripheral blood. Receiver operating
      characteristic (ROC) curve in combination with multivariate logistic regression
      was used to evaluate the diagnostic performance of the assays.Among a total of
      189 patients with suspected tuberculous pleurisy who were prospectively enrolled
      in this study, 177 patients were validated for inclusion in the final analysis.
      ROC analysis revealed that the area under the ROC curve (AUC) for T-SPOT.TB in
      pleural fluid and peripheral blood was 0.918 and 0.881, respectively, and for the
      ADA activity test in pleural fluid was 0.944. In addition, 95.5 spot-forming
      cells (SFCs)/2.5 * 10 cells were determined as the optimal cut-off value for T
      SPOT.TB in pleural fluid. Parallel combination of T-SPOT.TB and ADA activity test
      in pleural fluid showed increased sensitivity (96.9%) and specificity (87.5%),
      whereas serial combination showed increased specificity (97.5%). The combination
      of 3 assays had the highest sensitivity at 97.9%, with an AUC value of 0.964.T
      SPOT.TB in pleural fluid performed better than that in peripheral blood and the
      ADA activity test in pleural fluid for tuberculous pleurisy diagnosis. The
      optimal cut-off value of T-SPOT.TB in pleural fluid was 95.5 SFCs/2.5 * 10 cells.
      Combination of 3 assays might be a promising approach for tuberculous pleurisy
      diagnosis.

PMID- 29381919
TI  - Cystic fibrosis respiratory tract salt concentration: An Exploratory Cohort
      Study.
AB  - In cystic fibrosis patients, electrolytic and osmolality imbalance secondary to
      cystic fibrosis transmembrane conductance regulator mutations may impact on
      mucoid secretion accumulation and secondary colonization by opportunistic
      pathogens such as nontuberculous mycobacteria.We performed a noninvasive
      exploratory prospective controlled clinical study comparing sputum salinity and
      acid-base characteristics of cystic fibrosis and noncystic fibrosis control
      patients. A total of 57 patients and 62 controls were included.Sputum salt
      concentrations were 10.5 g/L (95% CI: 7.7-13.3) in patients and 7.4 g/L (95% CI:
      5.9-8.9) in aged-matched controls, a difference that was found to be
      statistically significant (P < .05). No difference in pH was observed between
      patients and controls.These differences in respiratory secretions salt
      concentrations could influence host-pathogen interactions in the context of
      cystic fibrosis respiratory infections. We propose to include respiratory
      secretion salt measurement as a routine analysis on cystic fibrosis patients'
      sputum submitted for bacterial culture.

PMID- 29381920
TI  - Corrective osteotomy with retrograde Fassier-Duval nail in an osteogenesis
      imperfecta patient with bilateral genu valgum: A case report.
AB  - RATIONALE: The treatment of osteogenesis imperfecta (OI) requires a
      multidisciplinary approach to maximize function and reduce fracture incidence.
      The aim of this case report was to discuss an alternative surgical approach to
      stabilize a corrective osteotomy using the Fassier Duval (FD) system in an OI
      patient. PATIENT CONCERNS: A 20-year-old OI woman presented with left thigh pain,
      gait disturbance, and bilateral genu valgus deformities. DIAGNOSES: Physical
      examination and standing radiographs revealed bilateral genu valgum with previous
      fixation implants in the femoral and the left tibia. INTERVENTIONS: Staged
      surgery was performed. A previous Ender pin was removed from the left femur, and
      a FD nail was inserted in a retrograde fashion. An intercondylar fracture was
      encountered while inserting the female rod in the distal left femur. After
      removal of a previous Rush pin from the right femur, several complications were
      also encountered during FD nailing of the right femur. The tip threads of the FD
      male nail could not achieve adequate anchorage in the region of the greater
      trochanter. To prevent male nail dropping, a horizontal stop Kirschner pin was
      inserted close to the distal end of the female nail. OUTCOME: Despite
      perioperative problems such as rod dropping and occurrence of an intercondylar
      fracture of the left distal femur, bilateral retrograde nailing using the FD
      system was successful. An accurate entry portal is important when performing
      retrograde rodding. In addition, reaming the portal to a larger diameter in order
      to accommodate the large head of the female nail can prevent intraoperative
      intercondylar split, especially when combined with an osteotomy at the distal
      femur. LESSONS: Selection of the proper surgical technique is dependent on both
      the surgeon's experience and the condition of the patient. Although not an
      optimal device, a FD nail can be used as an IM nail for corrective osteotomy at
      the distal femur in an adult OI patient with a small femoral IM canal.

PMID- 29381921
TI  - Immediate postoperative tracheal extubation in a liver transplant recipient with
      encephalopathy and the Mayo end-stage liver disease score of 41: A CARE-compliant
      case report revealed meaningful challenge in recovery after surgery (ERAS) for
      liver transplantation.
AB  - RATIONALE: Immediate postoperative tracheal extubation (IPTE) is one of the most
      important subject in recovery after surgery (ERAS) for liver transplantation.
      However, the criteria for IPTE is not uniform at present. PATIENT CONCERNS: We
      reported a successful IPTE in a liver transplant recipient with encephalopathy
      and a high Mayo end-stage liver disease (MELD) score of 41, which beyond the so
      called criteria reported in the literature. The patient was 48-year-old man,
      admitted in September 2016 for end-stage liver cirrhosis secondary to hepatitis
      B. DIAGNOSES: End-stage liver cirrhosis secondary to hepatitis B with
      encephalopathy and a high MELD score of 41. INTERVENTIONS: He was involved in our
      ERAS project and was extubated at the end of the liver transplantation in the
      operating room. OUTCOMES: As a result, the patient was not reintubated and had an
      excellent postoperative recovery, staying in intensive care unit (ICU) for just 2
      days and discharged home on day 10. LESSONS: We believed IPTE in liver transplant
      recipients with severe liver dysfunction is a meaningful challenge in ERAS for
      liver transplantation. Our case and literature review suggest 3 things: IPTE in
      liver transplantation is generally feasible and safe; the encephalopathy or high
      MELD score should not be the only limiting factor; and a more systematic
      predicting system for IPTE in liver transplantation should be addressed in future
      studies.

PMID- 29381922
TI  - Immediate versus deferred stenting for patients undergoing primary or emergent
      percutaneous coronary intervention: Protocol for a systematic review and meta
      analysis.
AB  - INTRODUCTION: Primary or emergent percutaneous coronary intervention (PCI) with
      stenting is the standard treatment for patients with ST-segment elevation
      myocardial infarction (STEMI) or non-STEMI acute coronary syndromes (ACS) at high
      risk. The value of delayed stenting following balloon-facilitated reperfusion in
      these patients is largely unknown. METHODS AND ANALYSIS: This systematic review
      aims to assess whether delayed stenting (vs immediate stenting) improves
      angiographic and cardiovascular clinical outcomes for patients with STEMI or non
      STEMI ACS undergoing primary or emergent PCI. The primary endpoint is adverse
      angiographic outcomes (no or slow coronary flow after final PCI), the main
      secondary endpoint includes a composite of long-term (>=6 months) all-cause
      mortality, recurrent ACS (recurrent myocardial infarction, unplanned
      revascularization of the target vessel, etc.), hospital admission for heart
      failure or any other cardiovascular cause. Relevant studies will be searched in
      the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and other
      electronic databases. Two authors will independently screen studies for
      inclusion, consulting with a third author where necessary to resolve
      discrepancies. The risk of bias of included studies will be assessed using the
      Cochrane Collaboration risk of bias tool, and quality of evidence using the
      Grades of Recommendation, Assessment, Development and Evaluation (GRADE)
      approach. Results will be presented using risk ratios with 95% confidence
      interval (CI) for dichotomous outcomes and standardized mean differences with 95%
      CI for continuous outcomes. ETHICS AND DISSEMINATION: This systematic review and
      meta-analysis protocol will not require ethical approval. We will disseminate the
      findings of this systematic review and meta-analysis via publications in peer
      reviewed journals.

PMID- 29381923
TI  - Identification of regulatory role of DNA methylation in colon cancer gene
      expression via systematic bioinformatics analysis.
AB  - Colon cancer arises from the accumulations of genetic and epigenetic changes.
      Currently, profiles of DNA methylation and gene expression of colon cancer have
      not been elucidated clearly. This articles aims to characterize the profile of
      DNA methylation and gene expression of colon cancer systemically, and acquire
      candidate genes potentially regulated by altered methylation for this
      disease.Data were downloaded from The Cancer Genome Atlas database.
      Differentially methylated CpG sites (DMCs) and differentially methylated regions
      (DMRs) were calculated via COHCAP. Differentially expressed genes (DEGs) were
      identified by DESeq2. Weighted gene co-expression network analysis (WGCNA)
      package in R was applied for WGCNA.Data of 275 solid tumor tissues and 19
      adjacent tumor tissues of colon cancer were obtained. A total of 1828 DMCs,
      including 1390 hypermethylated and 438 hypomethylated CpG sites, were identified
      between tumor and normal groups. A total of 789 DEGs, containing 435 upregulated
      genes and 354 downregulated genes were observed. It revealed that 8 DMRs-DEGs and
      95 DMCs-DEGs pairs were significantly correlated. Furthermore, genes of yellow
      and brown modules from WGCNA were significantly correlated with tumor/normal
      status, and significantly enriched in peroxisome proliferator activated receptor
      signaling pathway, glutamatergic synapse, and neuroactive ligand-receptor
      interaction. Genes in the above 2 modules were also significantly enriched in
      DMCs or DMRs-associated genes. Specifically, ADHFE1, HAND2, and GNAO1 were
      hypermethylated and downregulated in colon cancer, suggesting that the low
      expression levels of these genes may be regulated by DNA hypermethylation. In
      addition, the 3 genes were involved in brown module of WGCNA, indicating their
      important roles in colon cancer.The investigation of the relationship between DNA
      methylation and gene expression may help to understand the effect of DNA
      methylation alteration on genes expression, especially gene co-expression network
      in the development of colon cancer. Genes such as ADHFE1, HAND2, and GNAO1 may be
      served as potential candidates for diagnosis and therapy targets in colon cancer.

PMID- 29381924
TI  - Health and quality of life in patients with medication overuse headache syndrome
      after standardized inpatient rehabilitation: A cross-sectional pilot study.
AB  - The aim of this pilot study was to determine health-related quality of life
      (HRQoL) in patients with history of medication overuse headache (MOH) after
      detoxification and a headache-specific inpatient rehabilitation program and to
      receive necessary information for future prospective studies.HRQoL and headache
      related disability were cross-sectionally measured by Short Form 36 (SF-36),
      Hospital Anxiety and Depression Scale (HADS), Migraine Disability Score (MIDAS),
      Coping Strategies Questionnaire (CSQ), and Symptom Checklist 90 revised (SCL-90
      R). SF-36, HADS, and SCL-90-R data were compared to German population norms,
      stratified by age, sex, and comorbidities.Fifty-one patients (72.5% females, mean
      age 47.3 years) were included with an average headache duration of 25.3 years.
      Moderate to high levels of headache were reported on the MIDAS VAS at 6.51 (range
      0-10); SF-36 bodily pain was 40.3 (norm = 59.0, P < .001, 100 = best). Impaired
      functioning averaged at 78.4 (100 = no impairment) on the MIDAS. In contrast, SF
      36 physical functioning was comparable to the norm (mean: 78.4, norm = 81.8, P =
      .63). All other SF-36 scales were significantly lower than expected from the norm
      (all P < .001). The scales depression, anxiety, obsessive-compulsive, and
      interpersonal sensitivity were significantly affected, whereas the levels of SCL
      90-R schizophrenia nuclear and schizotypia were not lower than the norm. Coping
      with pain was moderate.This pilot study is the first that presents a
      comprehensive and simultaneously specific assessment of health and quality of
      life of MOH patients after detoxification and inpatient rehabilitation. Moderate
      to high levels of pain and self-reported disability owing to headache were
      observed, whereas physical function on the SF-36 was not different from the
      expected level of the norm. Mental health was substantially affected in several
      dimensions, which had been described to reduce the ability to cope with pain. MOH
      patients seem to have high expectations of functionality, low symptomatology, and
      intact well-being.

PMID- 29381925
TI  - Blood type AB predicts promising prognosis in gastric cancer patients with
      positive preoperative serum CEA.
AB  - Little is known about association between ABO blood groups and tumor markers in
      gastric cancer (GC) patients. The aim of the present study was to assess the
      prognostic value of ABO blood groups in GC patients with different levels of
      preoperative serum carcinoembryonic antigen (CEA).From September 2008 to April
      2015, a total of 3234 GC patients who received radical gastrectomy were
      retrospectively analyzed. The clinicopathological characteristics including ABO
      blood groups and preoperative CEA were recorded. The prognostic value of ABO
      blood groups within different levels of serum CEA was analyzed.Overall, the ratio
      of male to female patients was 3.5:1; the median age was 57.4 years (range 20
      87). The median overall survival (OS) for GC patients with blood type A, B, AB,
      and O were 52.6, 52.8, 53.8, and 53.6 months, respectively. There was no
      significant difference for the survival of patients among the 4 groups (P =
      .736). Also, no significant difference was found among the OS of the 4 blood
      types with negative (P = .875) and positive (P = .131) preoperative serum CEA.
      Further, we found that the OS of patients with positive preoperative serum CEA
      and blood type AB was significantly higher than that with blood type non-AB (P =
      .026). For patients with positive preoperative serum CEA, multivariate analysis
      showed that ABO blood groups were an independent prognostic factor.Blood type AB
      was a favorable prognostic factor for GC patients with positive preoperative
      serum CEA.

PMID- 29381926
TI  - The long-term survival benefits of high and low ligation of inferior mesenteric
      artery in colorectal cancer surgery: A review and meta-analysis.
AB  - BACKGROUND: The decision of ligation at the origin of the inferior mesenteric
      artery (IMA) or below the origin of the left colic artery (LCA) has remained a
      dilemma for surgeons in colorectal cancer surgery. The available studies are
      controversial. The objective of this meta-analysis is to compare the predictive
      significance of high versus low ligation in colorectal cancer surgery. METHODS: A
      literature search done using Medline, EMBASE, GoogleScholar, and references. A
      meta-analysis was performed to analyze the 5-year overall survival (OS) of the
      high and low ligation using hazard ratio (HR) and 95% confidence interval (CI).
      We further analyzed 2 subgroups considering the level of lymph nodes (LNs)
      extension. That is IMA positive (+ve) and negative (-ve) LNs. Survival
      differences were analyzed. RESULTS: A total of 3119 patients in 5 cohorts were
      included in this meta-analysis. The pooled HR results showed significant OS
      benefit of high ligation than low ligation (HR; 0.77, 95% CI: 0.66-0.89) in the
      "IMA +ve" group with 33% decreased risk, while there is no statistical
      significance in the "IMA -ve" (HR 0.66, 95% CI: 0.30-1.46) and the "all cases"
      group (HR 0.69, 95% CI: 0.41-1.15). CONCLUSION: The pooled data showed high
      ligation of IMA has a better survival benefit for the patients with IMA positive
      LNs. It signifies high ligation should be recommended for the advanced cases or
      with the suspected high risk of IMA lymphatic metastasis. The limited number of
      articles demands future high-powered, well-designed randomized controlled trials
      (RCTs) for the further reliable conclusion.

PMID- 29381927
TI  - Comparison of coblation annuloplasty and radiofrequency thermocoagulation for
      treatment of lumbar discogenic pain.
AB  - This study aimed to compare the effectiveness and safety of coblation
      annuloplasty and radiofrequency thermocoagulation for lumbar discogenic
      pain.Patients who suffered from lumbar discogenic pain and underwent coblation
      annuloplasty and radiofrequency thermocoagulation surgery were included. A
      questionnaire, including the visual analo scale (VAS), MacNab criteria, pain
      relief rate, and any complications due to surgery, was completed by the patients
      with the help of a trained volunteer who was blinded to the study. Data were
      collected at 1 week, and 1, 3, 6, and 12 months after surgery. Significant pain
      relief was defined as postoperative pain relief >=50% compared with the
      preoperative state. Any complications during or after surgery were also
      recorded.A total of 122 patients were included; 37 patients were lost in the
      follow-up and 85 were evaluated. Among these, 45 patients underwent coblation
      annuloplasty (CA group, n = 45) and 40 underwent radiofrequency thermocoagulation
      procedures (RF group, n = 40).VAS pain scores were decreased at 1 week and 1, 3,
      6, and 12 months postoperatively compared with preoperation in both groups (P <
      .05). The CA group had significantly lower VAS scores at 6 and 12 months of
      follow-up than did the RF group (P < .05). According to the modified MacNab
      criteria, the proportions of patients with excellent and/or good results at 3, 6,
      and 12 months of follow-up were significantly higher in the CA group compared
      with the RF group (P < .05).Only 2 patients reported soreness at the needle
      insertion site in the CA group. However, 3 patients had soreness at the needle
      insertion site, 3 had increased intensity of low back pain, 1 had intracranial
      hypotension, and 2 had new numbness in the leg and foot in the RF group. At the 1
      year follow-up, this numbness was present all of the time. No major complications
      occurred in the CA group.Our study suggests that CA is a more effective and safe
      minimally invasive procedure than RF for treating lumbar discogenic pain.

PMID- 29381928
TI  - Association of the IL-13 polymorphisms rs1800925 and rs20541 with chronic
      obstructive pulmonary disease risk: An updated meta-analysis.
AB  - The aim of this study was to investigate if 2 common single nucleotide
      polymorphisms (SNPs) in the interleukin-13 (IL-13) gene, rs1800925 and rs20541
      are associated with chronic obstructive pulmonary disease (COPD) risk.Case
      control association studies were retrieved systematically from PubMed, Scopus,
      ISI Web of Science, China National Knowledge Infrastructure, and Wanfang
      databases using standardized subject terms.Eleven studies including 3077
      participants (1896 cases and 1181 controls) were analyzed. Evidence for a
      positive association between the T allele of the IL-13 SNP rs1800925 and COPD
      risk was found in the overall population (odds ratio [OR] = 1.57, 95% confidence
      interval [95% CI]: 1.21-2.04, Pz = .001). In subgroup analysis according to
      ethnicity, the T allele of rs1800925 was associated with an increased risk of
      COPD in Asians (OR = 1.88, 95% CI: 1.23-2.87, Pz = .004) and Caucasians (OR =
      1.30, 95% CI: 1.01-1.67, Pz = .041), respectively. For rs20541, the results
      suggested an association between rs20541 and COPD risk in Caucasians under the
      recessive model (OR = 2.79, 95% CI: 1.13-6.92, Pz = .026), whereas this SNP was
      not associated with COPD in Asians.This meta-analysis suggests that the T allele
      of rs1800925 is associated with the increased risk of COPD in both Asians and
      Caucasians, whereas rs20541 is associated with the risk of COPD in Caucasians but
      not in Asians.

PMID- 29381929
TI  - Factors influencing the virological testing of cornea donors.
AB  - To assess the influence of donor, environment, and logistical factors on the
      results of virological testing of blood samples from cornea donors.Data from 670
      consecutive cornea donors were analyzed retrospectively. Logistic regression
      analysis was used to assess the influence of different factors on the results of
      virological testing of blood samples from cornea donors.The mean annual rate of
      donors with serology-reactive or not evaluable result was 14.8% (99 of 670)
      (range 11.9%-16.9%). The cause of donor death by cancer increased the risk of
      serology-reactive or not evaluable result (P = .0300). Prolonged time between
      death and post mortem blood removal was associated with a higher rate of serology
      reactive or not evaluable result (P < .0001). Mean monthly temperature including
      warmer months, differentiating between septic and aseptic donors, sex, and donor
      age had no significant impact on the results of virological testing of blood
      samples from cornea donors.The cause of donor death by cancer and a prolonged
      time between death and post mortem blood removal seem to be mainly responsible
      for serology-reactive or not evaluable result of blood samples from cornea
      donors. The percentage of discarded corneas caused by serology-reactive or not
      evaluable result may be reduced by shortening the period of time between death
      and post mortem blood removal.

PMID- 29381930
TI  - Chronic autoimmune disorders are increased in coeliac disease: A case-control
      study.
AB  - Coeliac disease (CD) is an autoimmune disorder of the small bowel associated with
      increased risk of additional autoimmune diseases (ADs).To investigate the
      prevalence of ADs in a population of adult coeliac patients.This was a
      retrospective case-control study. Data from coeliac patients and controls
      referred to a tertiary center between 2013 and 2016 were collected. The frequency
      of ADs and the unadjusted and adjusted odds ratios (ORs) for age, gender, disease
      duration, and body mass index with their 95% confidence intervals (CIs) were
      evaluated.Two hundred fifty-five patients with CD (median age 37.1 years; 206
      women) were matched with 250 controls. ADs were more frequent (35.3%) in coeliac
      patients than in controls (15.2%). Adjusted ORs for the presence of only 1, at
      least 1, and more than 1 AD were 3.13 (95% CI 1.81-5.42, P < .0001), 3.31 (95% CI
      2.00-5.46, P < .0001), and 3.93 (95% CI 1.49-10.36, P = .006), respectively.
      Hashimoto thyroiditis was the most prevalent AD (24.3% vs. 10%) OR = 2.55 (95% CI
      1.39-4.70, P < .0001), followed by psoriasis (4.3% vs. 1.6%), type 1 diabetes
      (2.7% vs. 0.4%), and Sjogren syndrome (2.4% vs. 0.4%).These findings suggest a
      need for a careful surveillance of autoimmune status, especially for Hashimoto
      thyroiditis in patients with celiac disease.

PMID- 29381931
TI  - Biomechanical evaluation of a novel integrated artificial axis: A finite element
      study.
AB  - Various modified instruments are used for the anterior reconstruction of the
      tumor lesion affecting the second cervical vertebra, but there have been no
      reports regarding individual integrated artificial axis (IAA) prosthesis
      fabricated by selective laser melting. In the present work, a new type of IAA
      prosthesis has been designed with a 3-dimensional (3D) finite element model of
      normal occiput-the fourth cervical vertebra being established to assess its
      biomechanics. For easy comparison, another 3D finite element model is also
      established for the T-shaped Harms cage and an additional posterior fixation was
      performed on each model. The models are tested under a preliminary loading of 40
      N to simulate cervical physical action including flexion, extension, lateral
      bending, and rotation. Under various loads from 4 different directions, the
      maximum stress and displacement of the IAA are less than those of the modified T
      shaped Harms cage. Except for flexion, the maximum stress of the third cervical
      vertebra endplate of the IAA is smaller than that of the modified T-shaped Harms
      cage. The new prosthesis with axis is a good choice for upper cervical operation,
      which not only can greatly increase the operation stability of the upper cervical
      segment but also could significantly reduce the risk of fixation failure due to
      Harms cage subsidence.

PMID- 29381932
TI  - Open reduction combined with CORA-based osteotomy of the ulna in the treatment of
      missed Bado type I Monteggia injury: A retrospective study of 5 cases.
AB  - Open reduction combined with ulnar osteotomy is the most common approach to
      treating missed Monteggia injuries. The osteotomy is usually performed at the
      proximal ulna to ensure better healing and fewer complications. The purpose of
      this study is to present a center of rotation angulation (CORA)-based osteotomy
      of the ulna for treating Bado type I Monteggia injuries.We retrospectively
      reviewed the cases of patients who were treated with open reduction combined with
      a CORA-based ulnar osteotomy between February 2014 and December 2016. Each
      patient provided his or her internal control, and paired data of the involved and
      uninvolved sides were analyzed to evaluate forearm rotation function.Five
      patients (3 male, 2 female) with median age 5.7 years (range, 3.4-6.8 years) were
      operated on by the senior author in our hospital. The median interval between the
      original injury and the corrective surgery was 3 months (range, 1-4 months). In a
      median follow-up of 10 months (range, 6-17 months), all patients obtained stable
      reduction of the radial head and uneventful healing of the ulnar osteotomy. All
      patients had pain-free elbows with no neurological or vascular complications and
      no implant breakage. Patients showed excellent outcomes evaluated using the
      Broberg and Morrey index.Open reduction with a CORA-based osteotomy of the ulna
      for the treatment of missed Bado type I Monteggia injury with an obvious ulnar
      bowing deformity resulted in stable reduction of the radial head and excellent
      forearm function.

PMID- 29381933
TI  - The diagnosis and endovascular therapy of renal artery aneurysm: A 32-patient
      case report.
AB  - RATIONALE: Renal aneurysm is a rare disease with the atypical symptoms and mostly
      diagnosed by imaging modalities. Endovascular therapy is a one of treatment
      methods. PATIENT CONCERNS: A retrospective analysis of 32 patients with renal
      artery aneurysm, from June 2010 to May 2016 in our hospital, was made in our
      study. All of them underwent therapy, and the effects and perioperative
      characteristics of it were analyzed. DIAGNOSIS: 32 patients were taken contrast
      enhanced CT and diuretic renal dynamic imaging to evaluate the state of illness.
      INTERVENTIONS: The preoperative blood creatinine, perioperative hemoglobin and
      relief of hypertension were performed. OUTCOMES: The preoperative blood
      creatinine was slightly increasing, while the perioperative hemoglobin was
      slightly decreasing. The relieving hypertension was performed in 9 of patients.
      LESSONS: Endovascular therapy is a mature and feasible treatment method. There is
      little effect on hemoglobin and renal function in postoperation, while it can
      also decrease the blood pressure.

PMID- 29381934
TI  - Pregnancy-associated hemophagocytic lymphohistiocytosis secondary to NK/T cells
      lymphoma: A case report and literature review.
AB  - RATIONALE: Hemophagocytic lymphohistiocytosis (HLH) occurs primarily in pediatric
      population, or secondary to malignancy, infection, or autoimmune disease. This
      disease is rare and prognosis is generally poor. Only a small number of cases
      during pregnancy have been reported in literature. PATIENT CONCERNS: We report a
      case of pregnancy-associated HLH secondary to natural killer (NK)/T cells
      lymphoma. She was admitted at 30 weeks and 3 days of pregnancy with complaints of
      abdominal pain and fever as high as 39.2 degrees C. The patient was found to have
      splenomegaly, pancytopenia, and acute hepatic failure. DIAGNOSES: A subsequent
      bone marrow biopsy revealed focal hemophagocytosis and atypical lymphoid cells.
      The splenic pulp also contained a large number of tissue cells proliferating and
      devouring mature red blood cells, lymphocytes, and cell debris. On the basis of
      these findings, we diagnosed the case as pregnancy-associated hemophagocytic
      lymphohistiocytosis secondary to NK/T cells lymphoma. INTERVENTIONS: Treatment
      consisted with dexamethasone and etoposide in combination with rituximab.
      OUTCOMES: Due to timely termination of pregnancy, the neonate was in good
      condition. However, the patient died on the 18th day postoperation due to
      multiorgan failure. LESSONS: We recommend that HLH be considered as differential
      diagnosis in a pregnant patient complaining of persistent fever, cytopenia, or
      declining clinical condition despite delivery of the baby. Prompt diagnosis and
      treatment is essential and fetal outcomes should also be considered. The decision
      to terminate a pregnancy and initiate chemotherapy during pregnancy with
      malignancy-associated HLH (M-HLH) needs to be further investigated in a larger
      cohort.

PMID- 29381935
TI  - Salvage chemoradiotherapy with cisplatin and vinorelbine for postoperative
      locoregional recurrence of non-small cell lung cancer.
AB  - Although a few investigators have demonstrated the effect of concurrent
      chemoradiotherapy (CRT) for postoperative recurrent non-small cell lung cancer
      (NSCLC), the outcome of this treatment remains unclear. The aim of this study was
      to elucidate the efficacy and tolerability of concurrent CRT with cisplatin
      (CDDP) and vinorelbine (VNR) in patients with postoperative locoregional
      recurrent NSCLC. A total of 40 patients who had received concurrent CRT with CDDP
      and VNR between January 1999 and December 2014 were retrospectively analyzed.
      Patients were treated with CDDP (80 mg/m on day 1) and VNR (20 mg/m on days 1 and
      8) every 4 weeks. Radiotherapy was administered concurrently during cycle 1. The
      delivered x-ray radiation dose was 60 Gy in all 37 patients who received x-ray
      radiotherapy; 3 patients received proton beam radiation (66 Gy [RBE] in 1 patient
      and 60 Gy [RBE] in 2 patients). The objective response rate was 85% (95%
      confidence interval [CI], 70.9%-92.9%). The median progression-free survival was
      20.3 months (95% CI, 12.9 months-not reached). The 2-year survival rate was 78.9%
      (95% CI, 63.0%-89.1%). The most common grade >=3 toxicity was neutropenia (18%).
      No grade >=3 radiation pneumonitis and no treatment-related deaths were
      observed.Our study revealed that concurrent CRT with CDDP and VNR was active and
      safe for patients with postoperative locoregional recurrent NSCLC. Salvage CRT
      for postoperative locoregional recurrent NSCLC might be a promising treatment for
      selected patients.

PMID- 29381937
TI  - Case of a cardiac arrest patient who survived after extracorporeal
      cardiopulmonary resuscitation and 1.5 hours of resuscitation: A case report.
AB  - RATIONALE: Per the American Heart Association guidelines, extracorporeal
      cardiopulmonary resuscitation should be considered for in-hospital patients with
      easily reversible cardiac arrest. However, there are currently no consensus
      recommendations regarding resuscitation for prolonged cardiac arrest cases.
      PATIENT CONCERNS AND DIAGNOSIS: We encountered a 48-year-old man who survived a
      cardiac arrest that lasted approximately 1.5 hours. He visited a local hospital's
      emergency department complaining of chest pain and dyspnea that had started 3
      days earlier. Immediately after arriving in the emergency department, a cardiac
      arrest occurred; he was transferred to our hospital for extracorporeal membrane
      oxygenation (ECMO). INTERVENTIONS: Resuscitation was performed with strict
      adherence to the American Heart Association/American College of Cardiology
      advanced cardiac life support guidelines until ECMO could be placed. OUTCOMES: On
      hospital day 7, he had a full neurologic recovery. On hospital day 58, additional
      treatments, including orthotopic heart transplantation, were considered
      necessary; he was transferred to another hospital. LESSONS: To our knowledge,
      this is the first case in South Korea of patient survival with good neurologic
      outcomes after resuscitation that lasted as long as 1.5 hours. Documenting cases
      of prolonged resuscitation may lead to updated guidelines and improvement of
      outcomes of similar cases in future.

PMID- 29381936
TI  - Genotype and clinical course in 2 Chinese Han siblings with Wilson disease
      presenting with isolated disabling premature osteoarthritis: A case report.
AB  - RATIONALE: Premature osteoarthritis (POA) is a rare condition in Wilson disease
      (WD). Particularly, when POA is the only complaint of a WD patient for a long
      time, there would be misdiagnosis or missed diagnosis and then treatment delay.
      PATIENT CONCERNS AND DIAGNOSIS: Two Chinese Han siblings were diagnosed as WD by
      corneal K-F rings, laboratory test, and mutation analysis. They presented with
      isolated POA during the first 2 decades or more of their disease course, and were
      of missed diagnosis during that long time. The older affected sib became disabled
      due to his severe osteoarthritis when he was as young as 38 years old. Two
      compound heterozygous pathogenic variants c.2790_2792del and c.2621C>T were
      revealed in the ATP7B gene through targeted next-generation sequencing (NGS).
      LESSONS: Adolescent-onset POA could be the only complaint of WD individual for at
      least 2 decades. Long delay in the treatment of WD's POA could lead to disability
      in early adulthood. Detailed physical examination, special biochemical test, and
      genotyping through targeted NGS should greatly reduce diagnosis delay in atypical
      WD patients with isolated POA phenotype.

PMID- 29381938
TI  - Osteopoikilosis found incidentally in a 17-year-old adolescent with femoral shaft
      fracture: A case report.
AB  - RATIONALE: Osteopoikilosis is a rare and asymptomatic disease of the bone, which
      is often discovered occasionally on radiography for irrelevant complaints.
      Characterized by multiple, small, circular, or oval-shaped radiodense lesions, it
      may be confused with bony metastatic tumors. PATIENT CONCERNS: The present study
      describes a case of a 17-year-old adolescent who suffered from pain and movement
      limitation of his left thigh following a fall from standing height. DIAGNOSES:
      Plain radiographs showed spiral fracture in left femoral shaft; besides, multiple
      scattered sclerotic lesions of variable size were also observed over the
      bilateral proximal femurs, left distal femur, proximal tibia, and distal tibia
      and fibula through X-rays, computed tomography, and magnetic resonance imaging.
      The patient was finally diagnosed with left femoral shaft fracture and
      osteopoikilosis. INTERVENTIONS: The patient underwent reduction and internal
      fixation with intramedullary nail a week after injury. OUTCOMES: The patient was
      discharged without any complications 12 days after the surgery. At the 3-month
      follow-up, the patient recovered well and remained symptom-free with no changes
      to his sclerotic lesions. LESSONS: Although this case is not so complicated, we
      have to be cautious when differentiating osteopoikilosis and bony metastases in
      clinical practice in future, which should avoid causing undue distress to both
      the patients and doctors.

PMID- 29381939
TI  - Utilizing flat-panel detector parenchymal blood volume imaging (FD-PBV) for
      quantitative kidney perfusion analysis during the process of percutaneous
      transluminal renal angioplasty (PTRA): A case report.
AB  - RATIONALE: Traditional digital subtraction angiography (DSA) provides lumen
      morphology of renal artery as indicators for vascular patency in patients with
      renal artery stenosis (RAS). It, however, lacks hemodynamic information toward
      target kidney. To solve this shortcoming, a novel technique, flat-panel detector
      parenchymal blood volume imaging (FD-PBV), is introduced, which is able to
      evaluate hemodynamic changes of target kidney intraoperatively. PATIENTS
      CONCERNS: A 77-year-old female presented with hypertension, intermittent
      dizziness, nausea, and fatigue. DIAGNOSES: Ninety-nine percent stenosis of left
      RAS was found. INTERVENTIONS: Percutaneous transluminal renal angioplasty was
      performed, along with FD-PBV acquisition protocol. OUTCOMES: Her symptoms
      relieved gradually after procedure. Intuitive FD-PBV maps showed her renal
      perfusion improved remarkably. Quantitative analysis of FD-PBV showed her kidney
      volume was 47.02 and 75.61 cm with average density of contrast medium (CM) 58.1
      HU and 311.5 HU before and after stenting. Follow-up at 6 months showed patency
      of the stent and stable kidney blood perfusion. LESSONS: FD-PBV technique
      possesses a remarkable value in quantitatively assessing the changes of kidney
      blood perfusion and can be a useful auxiliary technique for DSA.

PMID- 29381940
TI  - Topical steroids eye drops in conjunctival reactive lymphoid hyperplasia: Case
      report.
AB  - RATIONALE: Conjunctival lymphoproliferative lesions constitute a significant
      diagnostic challenge and it is essential to exclude neoplastic lesions.
      Histopathological and immunohistochemical tests are very useful in establishing
      the correct diagnosis. Reactive lymphoid hyperplasia (RLH) is part of a spectrum
      of lymphocytic infiltrative disorders. Evidence is scarce regarding appropriate
      treatment of conjunctival RLH. We report a case treated with topical
      corticosteroid. PATIENT CONCERNS: A 40 year-old female presented with a 7-month
      history of a slow growth tumor in the superior conjunctiva of the right eye. Slit
      lamp examination demonstrated salmon colored lesion in the upper conjunctiva,
      with little conjunctival injection, but no significant neovascularization. There
      was no eyelid involvement. DIAGNOSES: Ultrasound biomicroscopy showed lesion
      depth (1.53 mm) and larger diameter (10.73 mm). Pathological examination revealed
      a chronic inflammatory process with conjunctival folicular hyperplasia. The
      immunohistochemistry examination showed predominance of CD20, CD23, and CD 3 e CD
      5. INTERVENTION: We started topic prednisolone 1% 6 times daily. OUTCOMES: Six
      months after starting treatment, the lesion completely resolved, without any side
      effects or recurrence during three-year follow-up period. LESSONS: Conjunctival
      RLH can be managed in various ways, depending on patient symptonm, comorbities,
      and disease distribution. Surgical resection with cryotherapy, radiotherapy,
      systemic corticosteroids, subconjunctival triamcinolone, and rituximab are some
      options. There is no strong evidence in the literature of conjunctival RLH
      successfully treated with topical eye drops corticosteroid. In this report, we
      obtained completely resolution of conjunctival RLH with topical corticosteroid.
      CONCLUSION: Topical eye drops corticosteroids are an alternative treatment for
      selected cases of conjuncitval RLH with no orbital or eyelid involvement.

PMID- 29381941
TI  - Symptomatic adjacent segment disease after single-lever anterior cervical
      discectomy and fusion: Incidence and risk factors.
AB  - The purpose of this study was to determine the incidence and risk factors of
      symptomatic adjacent segment disease (ASD) following single-lever anterior
      cervical discectomy and fusion (ACDF) for cervical degenerative diseases.From
      January 2000 to December 2010, a total of 582 patients with cervical
      radiculopathy and myelopathy who had undergone single-lever ACDF surgery in the
      authors' institution were reviewed retrospectively. Patients who had a revision
      surgery for symptomatic ASD were selected for this study. The authors analyzed
      the incidence for ASD after single-lever ACDF. And univariate analysis and
      logistic regression analysis were performed to identify the risk factors of
      ASD.Among the 582 patients, 36 patients received subsequent surgical management
      for ASD after initial single-lever ACDF for an overall prevalence of 6.2%. The
      average onset time of ASD was 8.5 (2-15) years. The univariate analysis showed
      that there were no significant differences in sex, duration of disease, BMI, DM,
      smoking, operative levels, and follow-up period (P > .05) between the 2 groups
      with and without ASD. There were statistically significant differences in age at
      the time of operation (chi = 4.361, P = .037), and developmental canal stenosis
      (chi = 4.181, P = .041) between patients with and without ASD. The variables of
      age at the time of operation and developmental canal stenosis were included in a
      logistic regression model. The logistic regression analysis revealed that age at
      the time of operation <=50 years (P = .045, OR = 3.015, 95% CI = 1.024-8.882) and
      developmental canal stenosis (P = .042, OR = 2.797, 95% CI = 1.039-7.527) were
      the risk factors for ASD after single-lever ACDF.In the present study, the
      incidence of symptomatic ASD after single-lever ACDF was 6.2%. And the age at the
      time of operation <=50 years and developmental canal stenosis were the risk
      factors for ASD. The patients <=50 years old at the time of operation or with
      developmental canal stenosis are more likely to develop ASD after surgery, and
      the risk of reoperation will increase.

PMID- 29381942
TI  - Associations between dental anxiety and postoperative pain following extraction
      of horizontally impacted wisdom teeth: A prospective observational study.
AB  - The aim of the study is to identify associations between dental anxiety and
      postoperative pain in patients undergoing extraction of horizontally impacted
      wisdom teeth.A total of 119 volunteers provided demographic data, and completed
      questionnaires, the State-Trait Anxiety Inventory (STAI), Chinese Index of Dental
      Anxiety and Fear (C-IDAF)-4C, and the Numeric Rating Scale (NRS) for pain.Mean
      SAI, TAI, and C-IDAF-4C scores were 42.5 +/- 8.7, 46.4 +/- 10.9, and 16.9 +/-
      7.2, respectively. Mean postoperative pain level score was 3.0 +/- 1.8 (range:
      0.3-8.4). SAI scores increased as preoperative pain levels increased (beta =
      1.30, 95% confidence interval [CI]: 0.62-1.98, P < .001); females had higher SAI
      scores than males (5.34; 95% CI: 1.74-8.95, P = .004). Multivariable analysis
      revealed that females, bad exodontic experience, and higher predicted pain levels
      were associated with higher IDAF-4C scores. SAI scores (gamma = 0.611, P < .001)
      and TAI scores (gamma = 0.305, P < .001) increased as C-IDAF-4C scores increased.
      Higher C-IDAF-4C scores and longer operative time were significantly associated
      with higher levels of postoperative pain.Specific factors are associated with
      anxiety and stress, and postoperative pain in patients undergoing wisdom teeth
      extraction. Addressing these factors preoperatively may reduce stress and
      anxiety, and lead to more favorable treatment outcomes.

PMID- 29381943
TI  - Acute myeloid leukemia presenting as erythema nodosum: A case report.
AB  - RATIONALE: Erythema nodosum (EN), a type of septal panniculitis, could be a rare
      nonspecific cutaneous presentation of acute myeloid leukemia (AML). PATIENT
      CONCERNS: A 58-year-old Chinese female was admitted for a 4-week history of
      painful cutaneous lesions, accompanied by a sternal pain and fever. The lesions
      once resolved spontaneously but then recurred. Physical examination revealed
      warm, tender, indurated, rounded, erythematous to violaceous nodules in bilateral
      lower extremities, ranging in diameter from 1 to 6 cm. Blood marrow examination
      was compatible with AML-M2. DIAGNOSES: AML-M2 presenting as EN. INTERVENTIONS:
      Daunorubicin and cytarabine were used in induction chemotherapy. The patient
      achieved complete remission and her skin lesions disappeared simultaneously. Six
      courses of consolidation chemotherapy were conducted in the following 6 months.
      OUTCOMES: The patient died due to AML relapse. LESSONS: The case strengthens the
      awareness of cutaneous involvement of AML and raises oncological vigilance in
      patients with EN.

PMID- 29381944
TI  - Hemorrhagic pericardial effusion as the debut of acquired hemophilia in a chronic
      lymphocytic leukemia patient: A case report, and a review of acquired hemophilia
      A-related hematological malignancies.
AB  - BACKGROUND: Acquired hemophilia A (AHA) is a rare bleeding disease caused by
      autoantibodies against factor VIII. Spontaneous bleeding symptoms usually affect
      the skin and muscle, while pericardial effusion is an extremely rare
      manifestation. In the elderly, anticoagulant treatment is frequent and bleeding
      symptoms are usually associated with this. CLINICAL FINDINGS: We report a
      hemorrhagic pericardial effusion as the AHA debut in a patient with untreated
      chronic lymphocytic leukemia and anticoagulated with apixaban for atrial
      fibrillation and chronic arterial ischemia. The patient was treated with
      recombinant activated factor VII to control the active bleeding and
      corticosteroids and cyclophosphamide to eradicate the inhibitor. In addition, a
      briefly review of hematological malignancies associated to acquired hemophilia
      was performed. PARTICULARITIES:: a) anticoagulant treatment may confuse the
      suspicion of AHA and its diagnosis; b) hemorrhagic pericardial effusion is an
      extremely rare presentation; c) bypassing agents raise the risk of
      thromboembolism; d) hematological malignancies rarely cause AHA (<20% of cases).
      CONCLUSION: A multidisciplinary team is needed to diagnose and manage AHA
      effectively. The use of anticoagulants may lead to the misdiagnosis of clinical
      symptoms. Chronic lymphocytic leukemia is one of the main causes of hematological
      malignancies associated. The specific treatment of CLL is still recommended in
      the event of active disease.

PMID- 29381945
TI  - Development and clinical application of grading and classification criteria of
      lumbar disc herniation.
AB  - This study aimed to develop new grading and classification criteria for lumbar
      disc herniation (LDH). First, from January 1993 to January 2003, we collected the
      detailed information of 1127 patients with LDH and, based on that information,
      developed a new grading classification termed the 6-score-V-type criteria wherein
      conservative treatment is recommended for patients with type I, II, or IIIA,
      surgical treatment is recommended for type IIIC, IV, and V, and 3 months of
      conservative followed by surgery if no improvements are obtained during the
      conservative treatment period is recommended for type IIIBe. The distribution of
      types among the 1,127 patients was: type I (7.9%), type II (22.9%), type III
      (34.1%), type IV (22.2%), and type V (12.6%). Type III cases were subdivided into
      type IIIA (9.9%), type IIIB (13.3%), and IIIC (10.8%). Second, from February 2003
      to December 2009, we treated a separate group of 1130 patients with LDH according
      to this 6-score-V-type classification rubric and monitored them for 24 months.
      Therapeutic efficacy was assessed in 1130 patients with a standard evaluation for
      leg pain. Overall, 85.3% of the patients in the first year and 84.1% in the
      second year had good or excellent response ratings. The inter-examiner
      reliability was 98%. Assignment of therapeutic protocols according to the 6-score
      V-type classification yielded satisfactory outcomes, indicating that the 6-score
      V-type criteria are straightforward and practical.

PMID- 29381946
TI  - Efficacy and safety of 9 nonoperative regimens for the treatment of spinal cord
      injury: A network meta-analysis.
AB  - OBJECTIVE: This network meta-analysis aims to compare the efficacy and safety of
      9 nonoperative regimens (placebo, pregabalin, GM-1 ganglioside, venlafaxine
      extended-release [venlafaxine XR], fampridine, conventional over-ground training
      [OT], body-weight-supported treadmill training [BWSTT], robotic-assisted gait
      training [RAGT] + OT and body-weight-supported over-ground training [BWSOT]) in
      treating spinal cord injury (SCI). METHODS: Clinical controlled trials of 9
      nonoperative regimens for SCI were retrieved in the electronic database.
      Traditional pairwise and Bayesian network meta-analyses were performed to compare
      the efficacy and safety of 9 nonoperative regimens for the treatment of SCI.
      Weighted mean difference (WMD), odds ratios (OR), and surface under the
      cumulative ranking curve (SUCRA) were calculated using the Markov Chain Monte
      Carlo engine Open BUGS (V.3.4.0) and R (V.3.2.1) package gemtc (V.0.6). RESULTS:
      A total of 9 clinical controlled trials meeting the inclusion criteria were
      selected in this meta-analysis. On the aspect of efficacy, the results of
      pairwise meta-analysis indicated that the RAGT + OT and BWSOT might have the best
      efficacy in SCI patients in terms of a lower extremity motor score (LEMS)
      compared with conventional OT; the efficacy of RAGT + OT on SCI patients was
      relatively better than that of conventional OT in terms of walking index for
      spinal cord injury (WISCI). With the aspect of safety, the constipation rate of
      placebo on SCI patients was relatively higher than that of venlafaxine XR;
      however, with respect to headache and urinary tract infection, there was no
      significant difference in the safety of placebo, pregabalin, GM-1 ganglioside,
      venlafaxine XR, and fampridine on SCI patients. The results of SUCRA values
      suggested that BWSOT had the highest SUCRA value (75.25%) of LEMS; RAGT + OT had
      the highest SUCRA value (88.50%) of WISCI; venlafaxine XR had the highest SUCRA
      value (94.00%) of constipation; venlafaxine XR had the highest SUCRA value
      (80.00%) of headache; GM-1 ganglioside had the highest SUCRA value (87.75%) of
      urinary tract infection. CONCLUSION: Our results provide evidence that the RAGT +
      OT and BWSOT might have the best efficacy in the treatment of SCI, and the
      venlafaxine XR and GM-1 ganglioside showed adequate safety for SCI.

PMID- 29381947
TI  - Intrahepatic splenosis mimics hepatocellular carcinoma in a patient with chronic
      hepatitis B: A case report and literature review.
AB  - BACKGROUND: Splenosis is a benign and relatively uncommon condition caused by
      trauma or splenectomy or other procedures involving splenic tissue. It is usually
      asymptomatic, and often diagnosed accidentally, especially misdiagnosed as
      malignant tumor. METHODS: A 54-year-old man with prior history of chronic
      hepatitis B virus infection and underwent splenectomy for traumatic splenic
      rupture following a traffic accident 23 years previously was admitted to our
      hospital and found a hepatic mass in the right upper quadrant during an imaging
      examination. The diagnosis of his was not clear and finally he agreed to receive
      a surgical treatment. RESULTS: During the operation, we found a mass in the right
      posterior lobe of the liver and a hard nodule on the right side of the diaphragm,
      both were completely resected, and postoperative histopathologic examination
      revealed that all excised tissues were proved to have histological structure
      typical for the spleen. CONCLUSIONS: The occurrence of intrahepatic splenosis is
      rare with only few cases previously reported in the literature. It is a benign
      disease and sometimes difficult to distinguish from diseases of the liver. The
      need for positive surgical resection of splenosis is still controversial.

PMID- 29381948
TI  - Primary extraskeletal myxoid chondrosarcoma in cerebellum: A case report with
      literature review.
AB  - RATIONALE: Extraskeletal myxoid chondrosarcoma (EMC) is a rare malignant neoplasm
      of which intracranial EMC is the rarest. PATIENT CONCERNS: We present an unusual
      case report of a 41-year-old woman who was sent to the emergency department for a
      sudden headache and other symptoms related to increased intracranial pressure.
      INTERVENTIONS: Emergent CT revealed an occupying lesion in the left cerebellum
      with surrounding edema. A complete surgical excision of the lesion through a
      transcortical approach was performed. After the operation, this patient received
      adjuvant radiotherapy and temozolomide treatment. DIAGNOSES: Pathology diagnosis
      was an intracranial EMC. OUTCOMES: The patient survives with no tumor recurrence
      as of the last follow-up. Progression-free survival exceeded 20 months. LESSONS:
      We have reviewed the literature and here summarize the diagnosis and treatment
      options for intracranial EMC. Diagnosis and treatment options of this rare
      disease are discussed.

PMID- 29381949
TI  - Late-onset transient adrenal insufficiency in preterm twins with twin-to-twin
      transfusion syndrome: A case report.
AB  - RATIONALE: Late-onset transient adrenal insufficiency with circulatory collapse
      is a rare condition that occurs in preterm infants. Although the incidence of
      late-onset transient adrenal insufficiency in preterm infants has been reported
      in Japan, reports from Western countries are lacking. In addition, no study has
      investigated the effect of twin-to-twin transfusion syndrome (TTTS) in
      monozygotic twins. PATIENT CONCERNS: A pair of extremely low birth weight twins
      presented with TTTS. DIAGNOSES: Both twins developed late-onset adrenal
      insufficiency with oliguria, hypotension, hyponatremia, and pulmonary edema at a
      postnatal age of 24 days and 51 days, respectively. INTERVENTION: Temporary
      administration of intravenous hydrocortisone was initiated. OUTCOMES: Their
      symptoms improved dramatically and they survived the event without any neurologic
      sequelae after 3 years of follow-up. LESSONS: Late-onset circulatory collapse may
      occur, especially in extremely preterm infants, even at 2 months after birth.
      Hydrocortisone therapy is an effective treatment to rescue circulatory collapse
      caused by adrenal insufficiency in preterm infants and may not affect long-term
      neuromotor and cognitive outcomes.

PMID- 29381950
TI  - A 53-year-old man with a sclerosing rib lesion: A case report.
AB  - RATIONALE: Sclerosing osteomyelitis of Garre is a rare condition that occurs most
      commonly in tubular bones and the mandible. Its nontypical symptoms, low
      morbidity, and insidious process make its diagnosis difficult at an early stage.
      In this article, we reported a case of chronic sclerosing osteomyelitis which
      occurred in flat bone. PATIENT CONCERNS: A 53-year-old man was diagnosed with rib
      sclerosing osteomyelitis of Garre who had an 8-year course of intermittent local
      pain and swelling, which radiated toward the left side of his chest wall. Chest
      computed tomography (CT) showed irregular sclerosis of the diaphysis of the 10th
      rib, with periosteal reaction and narrowing of the medullary cavity, and magnetic
      resonance imaging (MRI) showed T2 heterogeneous low-signal intensity over the
      10th rib. DIAGNOSES: Based on the features of the clinical signs and radiography
      and biopsy of the lesion, diagnosis of rib sclerosing osteomyelitis of Garre was
      made. INTERVENTIONS: The patient was treated with surgical excision of a 10-cm
      long lesion after failed conservative treatment. OUTCOMES: Postoperatively, the
      patient achieved good functional recovery at the 10-year follow-up. LESSONS: Rib
      sclerosing osteomyelitis of Garre is an unusual condition and represents a
      noninfective course in the rib with a low morbidity. The surgical management was
      successful in relieving the patient's symptom.

PMID- 29381951
TI  - WATCHMAN device-related thrombus successfully treated with apixaban: A case
      report.
AB  - RATIONALE: Among atrial fibrillation patients with high risk of bleeding, left
      atrial appendage occlusion has emerged as an alternative to long-term oral
      anticoagulation therapy for stroke prevention. Device-related thrombus remains a
      major concern because it may result in recurrent embolic events. To date, there
      is no consensus on the optimal method of treating device-related-thrombus.
      PATIENT CONCERNS: A 78-year-old man with atrial fibrillation had an episode of
      intracranial hemorrhage while taking warfarin. He subsequently underwent
      percutaneous placement of a 30-mm Watchman device to the left atrial appendage.
      He was prescribed dual anti-platelet therapy with aspirin and clopidogrel.
      DIAGNOSIS: Reassessment echocardiography 3 months later found device-related
      thrombus. INTERVENTIONS: The antithrombotic regimen was switched from dual
      antiplatelet therapy to apixaban. OUTCOMES: Reassessment echocardiography 3
      months later revealed complete resolution of the device-related thrombus.
      Apixaban was stopped. He had dual antiplatelet therapy for 6 more months followed
      by life-long aspirin. There was no bleeding complication since implantation of
      Watchman device. LESSONS: We demonstrated successful treatment of device-related
      thrombus with a short course of apixaban with complete resolution of thrombus.
      Further randomized controlled trials are required to determine the choice and
      duration of drug therapy for device-related thrombus.

PMID- 29381952
TI  - Association between the number of natural teeth and diabetic retinopathy among
      type 2 diabetes mellitus: The Korea national health and nutrition examination
      survey.
AB  - The aim of this study was to investigate the relationship between the number of
      teeth and diabetic retinopathy among Korean population.This was a retrospective
      analysis using data of total 45,811 individuals who participated in the Korea
      National Health and Nutrition Examination Survey (KNHANES) 2008 to 2012. Among
      these, 2593 (5.7%) participants were identified as having type 2 diabetes
      mellitus. After excluding participants without ophthalmic evaluation or other
      variables, 2078 (80%) participants were included. Demographic factors including
      dental status were analyzed and compared between participants with and without
      diabetic retinopathy.Among the 2078 type 2 diabetes, 358 (17.2%) had diabetic
      retinopathy. Type 2 diabetes with fewer teeth were more likely to have diabetic
      retinopathy (P < .001). Multivariate analysis showed that type 2 diabetes with <
      20 teeth had an 8.7-fold risk of having vision-threatening diabetic retinopathy
      when compared with type 2 diabetes with >=28 teeth (95% confidence interval: 2.69
      28.3) after adjusting for age, sex, body mass index, smoking, drinking, exercise,
      hypertension, diabetes mellitus duration, and glycated hemoglobin level.The
      number of teeth was found to be an independent risk factor for diabetic
      retinopathy. Thus, a comprehensive approach of dentists and ophthalmologists is
      needed to minimize the complications of diabetes mellitus. Whether the teeth
      number reflects microvascular changes of the retina among type 2 diabetes
      warrants further investigation.

PMID- 29381953
TI  - Case report: an unusual case of Brugada syndrome combined with a ventricular
      septal defect: A case report.
AB  - RATIONALE: Brugada syndrome (BrS) is a cardiac ion channel disease that is caused
      by an autosomal dominant genetic abnormality. A ventricular septal defect is a
      common congenital heart disease, in which genetic defects play a significant
      role. PATIENT CONCERNS: We report an extremely rare case of a 42-year-old male
      with congenital heart disease, who suffered recurrent syncope and
      gastrointestinal bleeding. His electrocardiogram showed an unusual right bundle
      branch block-like pattern and ST-segment elevation in leads V1-V3. DIAGNOSES: The
      patient was eventually diagnosed with Brugada Syndrome Combined with a
      Ventricular Septal Defect. INTERVENTIONS: The patient was treated with ICD
      implants. OUTCOMES: We extracted his blood and performed whole exome sequencing.
      Whole exome sequencing revealed mutations in genes, which encode ion channels and
      proteins important for embryonic heart development. However, a novel mutation in
      the SCN5A gene was also found. LESSONS: To our knowledge, this is the first
      genetically proven case of BrS combined with a ventricular septal defect.

PMID- 29381954
TI  - Effect of MDR1 C1236T polymorphism on cyclosporine pharmacokinetics: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Cyclosporine (CsA) is one of the immunosuppressive drugs, whose
      pharmacokinetic characteristics vary greatly among individuals. The published
      data reveal conflicting effects of the polymorphism of MDR1 exon 12 SNP C1236T on
      the pharmacokinetics of cyclosporine.This study aims to conduct a meta-analysis
      to investigate the effect of SNP C1236T on the pharmacokinetics of cyclosporine.
      METHODS: A literature retrieval was conducted to find the relevant papers in
      databases including PubMed, Embase, Cochrane Library, China National Knowledge
      Infrastructure (CNKI), Wan Fang Database (Wan Fang), Chinese Biomedical
      Literature Database (CBM), VIP Database for Chinese Technical Periodicals (VIP)
      electronic source for published studies until January 2017. The pharmacokinetic
      parameters, including C0 (trough blood concentration), C2 (whole-blood levels at
      2 hours after drug intake), Cmax (the maximum concentration), and daily dose were
      extracted and a meta-analysis was performed by RevMan 5.3. RESULTS: A total of 11
      papers concerning 1361 individuals were included in the meta-analysis. As for
      dose adjusted C0, the results showed difference between subjects carrying CC
      genotypes and TT genotypes (MD: 6.76, 95% CI [2.38, 11.14], P = .02]. As for C2,
      the results showed significant difference between subjects carrying CC genotypes
      and CT genotypes (MD: -18.50, 95% CI [-35.49, -1.52], P = .03), as well as CC
      genotypes and TT genotypes (MD: -19.01, 95% CI (-35.85, -2.16), P = .03). As for
      Cmax, daily dose, and C0, the overall results showed no major influence.
      CONCLUSIONS: MDR1 C1236T polymorphism may have a minor effect on cyclosporine
      pharmacokinetics in transplantation patients.

PMID- 29381955
TI  - Spontaneous internal hemorrhage of a giant hepatic hemangioma: A case report.
AB  - RATIONALE: Hepatic hemangioma, a benign liver tumor, can rarely spontaneously
      rupture and hemorrhage, which is then associated with significant mortality. The
      diagnosis of internal hemorrhage is challenging and the management is disputed.
      PATIENT CONCERNS: We describe the case of a 52-year-old female patient with chief
      complaints of fever and anemia, with no history of recent trauma. DIAGNOSES:
      Ultrasound suggested the possibility of a liver abscess and computed tomography
      (CT) examination revealed a giant space occupying lesion (SOL) (approximately 16
      cm) in the right hepatic lobe, indicating a hepatic tumor or abscess. The patient
      did not respond to antibiotics and blood transfusion. Liver needle biopsy
      revealed blood clots suggestive of intratumoral hemorrhage, possibly of a hepatic
      hemangioma. INTERVENTIONS: Interventional radiologic approach revealed active
      bleeding at the phrenic artery that supplied the liver SOL. Thus, embolization
      was performed and re-angiography showed no active bleeding from the embolized
      vessel. The patient became afebrile, but fever recurred the next day. Hence, an
      exploratory open right hemihepatectomy was undertaken and the intraoperative
      frozen biopsy confirmed hepatic hemangioma with internal hemorrhage, but
      malignancy could not be excluded for some focal tissues. Postoperative pathology
      report confirmed the diagnosis of hepatic hemangioma with internal hemorrhage and
      excluded malignancy. OUTCOMES: The fever subsided and the patient was discharged
      in good health. A follow-up CT performed three months, postoperatively, indicated
      compensatory growth of the left hepatic lobe. LESSONS: This case demonstrates
      that the diagnosis of hepatic hemangioma with internal hemorrhage can be
      confirmed by needle biopsy and surgical resection is the optimal treatment for
      such a lesion.

PMID- 29381956
TI  - 18F-Fluorodeoxyglucose positron emission tomography computed tomography detection
      threshold in follicular lymphoma: A case report.
AB  - RATIONALE: Follicular Lymphoma in situ is generally identified as reactive
      follicular hyperplasia in which some of the hyperplastic germinal centers are
      colonized by few lymphoma cells. These cells can be detected through their strong
      18F-Fluorodeoxyglucose avidity. PATIENT CONCERNS: We report the case of a 70 year
      old patient with arthralgia, weight loss and chronic fever over two months. A
      paraneoplastic polymyalgia rheumatica was initially suspected on abnormal 18F
      fluoro-deoxyglucose positron emission tomography (PET) pictures in two inguinal
      lymph nodes with a standardized uptake value at 8.6 and 5.8. DIAGNOSES: The PET
      lymph nodes were removed and histological examination revealed subtle lymph nodes
      infiltration by follicular lymphoma in situ. The absolute number of the
      follicular lymphoma cells determined using virtual imaging and 3D reconstruction
      appeared very low with a total tumor cell volume estimated at around 0.026 mm for
      one lymph node and 0.041 mm for the other. INTERVENTIONS: The patient has been
      treated by corticotherapy alone. OUTCOMES: A long-time follow-up should be highly
      suggested for this patient to avoid any risk of clinical progression to
      follicular lymphoma. LESSONS: Our findings show that low amounts of follicular
      lymphoma cells in reactive germinal center may reach a threshold of
      hypermetabolism detectable with positron emission tomography imaging, suggesting
      that tumor microenvironment also accounts for such as strong fluoro-deoxyglucose
      avidity. Thus, a systematic immunohistochemistry with anti-BCL2 antibodies should
      be performed on PET positive lymph node with apparent normal morphological
      features.

PMID- 29381957
TI  - Ectopic thyroid of the pancreas: A case report and literature review.
AB  - RATIONALE: Ectopic thyroid is commonly found in the neck region. Intra-abdominal
      ectopic thyroid is extremely rare, with only 2 cases reported in the pancreatic
      region. Very few reports have described detailed imaging findings of intra
      abdominal ectopic thyroid. PATIENT CONCERNS: A 73-year-old woman with aggravated
      recurrent right upper quadrant pain was found to have a retroperitoneal mass at
      the head of pancreas. Abdominal computed tomography (CT) showed a well-defined,
      high attenuated (56HU) mass measured of 60 * 50 mm in diameter, that exhibited
      heterogeneous contrast enhancement throughout the 3 phases. DIAGNOSIS:
      Neuroendocrine neoplasm was suspected. INTERVENTIONS: Following discussions with
      the patient, she refused fine needle aspiration cytology; however, she underwent
      total resection of the mass and had an uneventful clinical course.
      Histopathological examination showed thyroid tissue with TTF-1 and TGB
      positivity, and BRAF negativity, indicating a benign variant. OUTCOMES: The
      patient had no signs of relapse with normal thyroid hormone levels after 2 years
      of follow up. LESSONS: Ectopic thyroid tissue should be considered when patients
      present with similar imaging findings in abdomen. We review all reported cases of
      abdominal ectopic thyroid tissue to provide specific evidence for the diagnosis
      and treatment of this rare entity.

PMID- 29381958
TI  - Should we consider IgG hypogammaglobulinemia a risk factor for severe
      complications of Ludwig angina?: A case report and review of the literature.
AB  - RATIONALE: Cervical necrotizing fasciitis (CNF) and descending necrotizing
      mediastinitis (DNM) are rare forms of complication of Ludwig angina. These
      potentially lethal infections are difficult to recognize in early stages and are
      often associated with predisposing factors like diabetes and immunocompromised
      states. Moreover, IgG hypogammaglobulinemia (hypo-IgG) is considered to be a risk
      factor of mortality in patients with septic shock; however, it is not routinely
      quantified in patients with extremely serious infections, particularly in cases
      with no history or evidence of immunocompromising disorders. PATIENT CONCERNS: We
      present a case of a 58-year-old woman who survived Ludwig angina, complicated by
      CNF and DNM. Despite a rapid diagnosis, aggressive surgical debridement and broad
      spectrum antibiotics, the infection and necrosis advanced, requiring multiple
      surgical interventions and long intensive care unit (ICU) support. CONCLUSION: We
      hypothesize that detecting a low level of endogenous IgG and treating with
      adjuvant passive immunotherapy was key in determining a favorable outcome.

PMID- 29381959
TI  - IgG4-related cerebral pseudotumor with perineural spreading along branches of the
      trigeminal nerves causing compressive optic neuropathy: A case report.
AB  - RATIONALE: Immunoglobulin G4-related disease (IgG4-RD) is characterized by tumor
      like lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma
      cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD has been described
      in a variety of organ systems; however, it rarely involves the central nervous
      system. PATIENT CONCERNS: A 17-year-old woman visited our clinic with a complaint
      of blurred vision for the past 5 months. She also reported a painless right
      submandibular mass that had been present for 1 year. Her best-corrected visual
      acuity (BCVA) was 2.0 LogMAR, with an almost total visual field defect in the
      right eye. DIAGNOSES: Magnetic resonance imaging (MRI) revealed lobulated
      parasellar tumors with perineural spreading along branches of the trigeminal
      nerves causing right optic nerve compression. A craniotomy with tumor removal and
      submandibular gland biopsy was performed. Histopathological analysis of the tumor
      revealed stromal fibrosis with atypical lymphoid infiltrations. Histopathological
      and immunohistochemical analysis of the submandibular gland confirmed the
      diagnosis of IgG4-RD. INTERVENTIONS: The patient was administered 500mg/d of
      pulse methylprednisolone for 3 days, 500mg of intravenous rituximab every 2 weeks
      (for a total of 2 doses), and 500mg of intravenous pulse cyclophosphamide every
      month (for a total of 3 doses). OUTCOMES: Two months after the initiation of
      immunosuppressive therapy, the patient's BCVA returned to 0.1 LogMAR with visual
      field defect recovery. The follow-up MRI showed the almost complete disappearance
      of the previously contrast-enhanced lesions. LESSONS: Herein, we report a rare
      case of IgG4-RD presenting as a parasellar tumor and present a review of the
      related literature. Based on the case report, we propose that aggressive therapy
      with glucocorticoid, rituximab, and cyclophosphamide may potentially be useful
      for treating such cases.

PMID- 29381961
TI  - Rare metastasis to paranasal sinuses from triple-negative breast cancer: A case
      report and literature review.
AB  - RATIONALE: Breast cancer, the most common form of cancer among women, rarely
      metastases to the head and neck region. To date, there have been only 6 similar
      cases in the literature, and most patients in these reports had very poor
      prognosis. PATIENTS CONCERNS: We report a 61-year-old female presented pain and
      numbness on the right side of the face 5 years after being diagnosed with triple
      negative breast cancer. DIAGNOSIS: Magnetic resonance imaging (MRI) revealed a
      tissue mass in the sphenoid sinus. The tissue biopsy confirmed metastasis of
      breast cancer. INTERVENTION: The patient received initial chemotherapy and
      radiotherapy plus 10 cycles of maintenance chemotherapy OUTCOMES:: The patient
      got long-term progression-free survival time. The total time to progression was
      32 months. LESSONS: Although breast cancer rarely metastasizes to the head and
      neck region, awareness should be raised when breast cancer patients experience
      headache or have sinus-related symptoms. Chemotherapy and radiotherapy may be
      effective to treat paranasal sinus metastasis of triple-negative breast cancer,
      and patients may achieve long-term survival.

PMID- 29381960
TI  - Disabling tremor induced by long-term use of sodium valproate and lamotrigine:
      Case report.
AB  - RATIONALE: Sodium valproate (VPA) and lamotrigine (LTG) are widely used
      antiepileptic drugs, disabling postural, and action tremors after using LTG with
      VPA were reported in 1993. However, in this study, we describe a patient in whom
      disabling resting-type tremor induced by 2-year use of VPA and LTG. PATIENT
      CONCERNS: A 50-year old man was referred to department of neurology because of
      involuntary upper limbs resting-type tremor with high amplitude that had begun 6
      months previously and progressively worsened, and he could not work on the day of
      visit. Furthermore, he had been treated with VPA, LTG, and benzhexol for 2 years
      as he suffered from twitch of eyelids and facial region, and amantadine,
      monolithic compound preparation (flupentixol and melitracen) were added in the
      last 2 months because of tremor and anxiety. However, the treatment had no
      benefit on improving involuntary movements of the patient. DIAGNOSES: Drug
      induced disabling tremor was diagnosed. INTERVENTIONS AND OUTCOMES: LTG,
      amantadine, and VPA were withdrawn, the remaining 2 drugs, benzhexol and compound
      preparation (flupentixol and melitracen), were continued to use, and the patient
      improved in 2.5 months after discontinuation of 3 drugs. There was no recurrence
      at 6 months follow-up. LESSONS: Considering the wide and long-term utilization of
      VPA and LTG, healthcare providers should be aware of them as a possible cause of
      tremor. When necessary, an attempt of discontinuing the suspected drugs should be
      made to confirm the diagnosis, instead of symptomatic treatment, especially when
      the adverse event was severe and fatal.

PMID- 29381962
TI  - Effects of treatment with chemotherapy and/or tamoxifen on the biomarkers of
      cardiac injury and oxidative stress in women with breast cancer.
AB  - There has been an increase in deaths from cardiovascular diseases following
      breast cancer therapy. Evidence has shown that this outcome is, in part,
      associated with cardiotoxicity induced by the chemotherapeutic drugs and the
      increase in oxidative stress. The aim of this study was to evaluate the effects
      of chemotherapy and hormone therapy with tamoxifen on the biomarkers of cardiac
      injury and oxidative stress in women with breast cancer.Thirty women were
      followed-up for 1 year and were divided into 3 groups according to the treatment
      protocol: women treated only with tamoxifen and clinical follow up for 12 months
      (Tam, n = 10); women treated only with chemotherapy for 6 months with clinical
      follow up for an additional 6-month period (Chemo, n = 10); and women who
      received chemotherapy for 6 months followed by a 6-month period only with
      tamoxifen therapy and clinical follow up (Chemo + Tam, n = 10). Analysis of the
      blood levels of cardiac troponin I (cTnI), advanced oxidation protein products
      (AOPP) and the activity of the plasmatic isoform of the antioxidant enzyme
      glutathione peroxidase (GPx) was performed before treatment (T0) and at 6 (T6)
      and 12 (T12) months after treatment.The Chemo group showed higher levels of cTnI
      (0.065 +/- 0.006 ng/mL, P < .05) and AOPP (4.99 +/- 0.84 MUmol/L, P < .05) and
      reduced GPx activity (24.4 +/- 1.1 nM/min/mL, P < .05) at T12 than the Tam group
      (cTnI: 0.031 +/- 0.001 ng/mL; AOPP: 1.40 +/- 0.10 MUmol/L; GPx: 28.0 +/- 0.7
      nM/min/mL) and Chemo + Tam group (cTnI: 0.037 +/- 0.002 ng/mL; AOPP: 2.53 +/-
      0.30 MUmol/L; GPx: 29.5 +/- 1.0 nM/min/mL).These data support the hypothesis that
      long-term oxidative stress after chemotherapy may have an impact on
      cardiovascular diseases and that tamoxifen has cardioprotective effects.

PMID- 29381963
TI  - Apatinib concurrent gemcitabine for controlling malignant ascites in advanced
      pancreatic cancer patient: A case report.
AB  - RATIONALE: Malignant ascites (MA) is one of the poor prognostic factors for
      advanced pancreatic cancer and can bring about serious symptoms. The improvement
      of quality of life for patients is priority. However, there is no standard method
      for the treatment for pancreatic cancer-mediated MA. Apatinib is a novel and
      highly selective tyrosine kinase inhibitor targeting vascular endothelial growth
      factor receptor-2. There are no reports of concurrent apatinib with gemcitabine
      in patients with pancreatic cancer-mediated MA. PATIENT CONCERNS: Herein, we
      presented a 64-year-old man patient who visited hospital due to abdominal pain
      for 1 month. DIAGNOSES: He was initially diagnosed with pancreatic cancer and his
      first symptom was MA. INTERVENTIONS: After failing in tube drainage and
      gemcitabine therapy, the patient received gemcitabine combined apatinib orally
      and after administrated 1 month, the MA was evaluated as nearly clear response
      according to the RECIST 1.1 standard, and without further need of paracentesis.
      The CEA and CA199 reached the lowest level after administrating for 2.5 months
      during the treatment process. OUTCOMES: 10.5 months following apatinib
      administration, the patient achieved a progression-free survival for more than 11
      months. Hypertension (grade IV), hand-foot syndrome (grade I) and proteinuria
      (grade II) were observed. LESSONS: It indicated that apatinib concurrent
      gemcitabine may be a superior choice for pancreatic cancer-mediated MA. Further
      clinical trials required to confirm its efficacy and safety.

PMID- 29381964
TI  - Treatment of aggressive prolactinoma with temozolomide: A case report and review
      of literature up to date.
AB  - RATIONALE: Aggressive pituitary adenomas and pituitary carcinomas are rare and
      demand multiple treatment strategies. Temozolomide, an orally active alkylating
      chemotherapeutic agent, has recently been recommended as a salvage medication for
      refractory pituitary adenomas or carcinomas. PATIENT CONCERNS: A 17-year-old male
      presenting with aggressive prolactinoma that continued to progress despite
      surgery, gamma knife, and dopamine agonists. DIAGNOSES: The diagnosis of
      refractory aggressive prolactinoma was made on the basis of clinical findings and
      the lack of efficacy of conventional treatment. INTERVENTIONS: The patient
      received the most frequently recommended regimen of temozolomide treatment for 22
      cycles. OUTCOMES: Temozolomide resulted in a remarkable shrinkage of tumor mass
      and inhibition of prolactin secretion and this patient's clinical condition
      improved progressively. LESSONS: Temozolomide can be used as a salvage treatment
      to refractory pituitary tumors and o(6)-methylguanine-DNA methyltransferase
      (MGMT) status is a significant predictor to the effectiveness of temozolomide
      based on the existing literature.

PMID- 29381965
TI  - Urachal borderline mucinous cystadenoma: A rare case report and literature
      review.
AB  - RATIONALE: Urachal borderline mucinous cystadenoma is very rare and has only 9
      cases in the current literature with the biological behavior between adenoma and
      adenocarcinoma. PATIENT CONCERNS: We reported a 41-year-old man with moderate
      lower abdominal pain, and the imaging examination found an irregular cystic
      lesion extending from umbilicus to the dome of urinary bladder with significant
      separations and calcifications. DIAGNOSES: The diagnosis was confirmed according
      to the specific anatomical location and pathological examination which was proved
      as mucinous cystadenoma with low malignant potential. INTERVENTIONS: The patient
      undertook radical excision and partial cystectomy. OUTCOMES: His postoperative
      condition was good. LESSONS: Urachal borderline mucinous cystadenoma can be
      located by image examination, which may also offer several diagnostic tips
      according to separation, calcification, and enhancement in computed tomography
      scan. When combined with pathological findings, qualitative diagnosis can be
      determined. Surgical resection should be chosen as an optimal treatment. Our
      present study reviewed the clinical and biological information of all previous
      cases which were diagnosed as urachal borderline mucinous cystadenoma and we
      supplemented more data for further study.

PMID- 29381966
TI  - Hemolytic anemia in alcoholic liver disease: Zieve syndrome: A case report and
      literature review.
AB  - RATIONALE: Zieve syndrome, a rarely reported disease resulting from alcohol
      abuse, consists of a triad of symptoms: hemolytic anemia, cholestatic jaundice,
      and transient hyperlipidemia. It is largely under-recognized and under-reported,
      possibly because of unawareness of the condition by physicians. Here, we report a
      case of Zieve syndrome managed at the Jilin University First Bethune Hospital.
      PATIENT CONCERNS: A 30-year-old Chinese woman presented with a 4-month history of
      fatigue, yellowish discoloration of the eyes, and tea-colored urine. She had been
      a heavy drinker for 2 years prior to onset of the disease with an average daily
      alcohol intake of 60 g/d and more than 80 g/d for the previous 6 months.
      DIAGNOSIS: The diagnosis of Zieve syndrome was confirmed based on hemolysis and
      cholestatic jaundice secondary to alcoholic liver disease and heavy drinking.
      Bone marrow biopsy and liver biopsy both supported the diagnosis. INTERVENTIONS:
      We treated her with abstinence from alcohol and supportive therapy. OUTCOMES: The
      patient was discharged 14 days after admission with an improvement in symptoms,
      which continued to subside during the 2-month follow-up period. LESSONS: Doctors
      confronted with hemolysis in a patient with alcoholic liver disease should be
      aware of the under-reported Zieve syndrome. Recognition of this syndrome could
      help doctors avoid unnecessary invasive procedures and emphasize the importance
      of alcohol abstinence as the mainstay of management. Glucocorticoids may not be
      useful in treating hemolytic anemia in Zieve syndrome.

PMID- 29381967
TI  - Responses to crizotinib and disease monitoring with circulating tumor cells in
      lung adenocarcinoma patient with MET exon 14 skipping mutation: A case report.
AB  - RATIONALE: Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutation
      was a targetable alteration in nonsmall-cell lung cancer (NSCLC), and the MET
      inhibitor of crizotinib had the most efficacy among all the targeted drugs. Most
      of the cancer-related deaths are associated with metastasis. Circulating tumor
      cells (CTCs) have been a valuable biomarker in assessing metastasis. Recent
      experiences suggested that CTCs detection may help improve diagnosis and predict
      prognosis for patients with NSCLC. However, few literatures have reported the
      CTCs detection based on the (MET) exon 14 skipping, which are positive in NSCLC
      patients. PATIENT CONCERNS: The patient, a 69-year-old Chinese male, with a 50
      years history of smoking. Because of the cough, the patient went to the hospital
      and found the upper right lung tumor and the right supraclavicular lymph node
      enlarged. He was worried that it was cancer. DIAGNOSES: The patient was performed
      biopsy of the right clavicle lymph node metastasis on October 12 and sent the
      tissue specimen for pathological evaluation. Finally, the patient was diagnosed
      to be with a pT3N3Mx stage IIIC lung adenocarcinoma. INTERVENTIONS: The patient
      began to take orally crizotinib 250 mg twice a day for the medical therapy after
      lymph node biopsy. At the same time, the CTCs were detected to observe the
      prognosis of the patients. OUTCOMES: Compared with the first CTCs result, the
      second test revealed a decrease in the amount of CTCs, while the mesenchymal CTCs
      have increased, indicating the possibility of distal metastasis. LESSONS: This is
      the first proof that CTCs can be quantitatively assayed by MET exon 14 skipping
      mutation, which demonstrates the clinical response to crizotinib. More cases
      should be reported and further evaluation for treatment options and prognosis
      evaluation is necessary.

PMID- 29381968
TI  - The polymorphism of rs266729 in adiponectin gene and type 2 diabetes mellitus: A
      Meta-Analysis.
AB  - Genome-wide association studies and meta-analyses indicate that the polymorphism
      of rs266729 in adiponectin gene increases the risk of type 2 diabetes mellitus
      (T2DM); however, these study methods have not been able to identify the
      underlying genetic effect on the development of T2DM. A genetic model-free
      approach was conducted to determine the underlying genetic model of inheritance
      of T2DM because of rs266729 in adiponectin gene.We searched available studies on
      the association between the rs266729 in adiponectin gene and T2DM in accordance
      with the inclusion and exclusion criteria. Based on the information extracted
      from the studies, generalized odds ratio value (GOR) was used to evaluate whether
      the rs266729 polymorphism was a risk factor for T2DM. The parameter lambda was
      calculated to estimate the genetic model, which was defined as the quotient of
      natural logarithm odds ratio of GC to CC divided by the natural logarithm odds
      ratio of GG to CC. Finally, binary logistic regression analysis was used to
      calculate the genetic effect of rs266729 on T2DM.Data from 7 studies were
      included in this meta-analysis. The total number of subjects was 12,323,
      comprising 5,948 cases and 6,395 controls. Mean (standard deviation) age of cases
      was 59.50 (11.53), and that of the controls was 53.80 (11.65), whereas the
      proportion of male was 40.9 and 50.0%, respectively. GOR was 1.13 (1.02, 1.25)
      and lambda was 0.47 (0.29, 0.64). The result of logistic regression indicated
      that the G allele influenced the development of T2DM in the additive model,
      whereas the genetic effect was 1.13 (1.06, 1.19). Sources of control populations
      were the cause of between-study heterogeneity; nonetheless, there was no
      publication bias among studies.The G allele of rs266729 in adiponectin gene
      increases the risk of T2DM through an additive genetic model with an effect of
      1.13 (1.06, 1.19).

PMID- 29381969
TI  - HPV types in cervical cancer tissue in South Africa: A head-to-head comparison by
      mRNA and DNA tests.
AB  - Accurate identification of human papillomavirus (HPV)-types in cervical cancer
      tissue may be important for tailoring tests for primary screening and types to be
      included in a vaccine. The aim of this study was to compare test-performance of a
      45-type HPV deoxyribonucleic acid (DNA)-test with a 9-type HPV messenger
      ribonucleic acid (mRNA)-test in cervical cancer tissues.In a case-series design
      188 women with diagnosed cervical cancer during the period January 2008 to July
      1, 2011 at the Gynaecological Oncology Unit, University of Pretoria, South Africa
      were recruited to the study. After cases with negative internal controls for
      DNA/mRNA detection (n = 18) and unconfirmed histology (n = 3) of cervical cancer
      were excluded, 167 women remained eligible for analysis. We compared 45 DNA-types
      detected through general primer (GP)5/6 polymerase chain reaction (PCR) and
      reverse line blot (RLB) genotyping with a modified version of the mRNA test
      PreTect HPV-Proofer detecting 9 genotypes (16, 18, 31, 33, 35, 45, 51, 52,
      58).Histological types were 92.2% squamous cell carcinoma, 4.8% adenocarcinoma,
      and 3.0% adenosquamous carcinoma. Overall, HPV was detected in 95.2% (159/167) of
      specimens. The DNA- and mRNA tests each rendered 153/167 (91.6%) HPV positive
      results. When restricting the analysis to the 9 high-risk HPV-types included in
      the mRNA test, 91.6% (153/167) and 88.0% (147/167) were positive by the mRNA- and
      DNA-tests (P = .28), respectively. After hierarchical categorization of 9
      comparable types, we found concordance in 66 of 67 specimens for HPV16, 25 of 27
      specimens for HPV18, 19 of 21 specimens for HPV45, and only in 33 of 45 for
      HPV31, 33, 35, 51, 52, 58. The positivity rate for the HPV types 16, 18, and 45
      and the positivity rate for HPV 16, 18, 45, 33 and 35 by both tests was 66% to
      68% and 80% to 83%, respectively.Overall and when considering established high
      risk types, the mRNA test has at least as high detection rate as the DNA test.
      The mRNA test can be an appropriate research tool to describe causative HPV-types
      in cervical cancer tissue for health care planning purposes.

PMID- 29381970
TI  - Impact of diabetes mellitus and chronic liver disease on the incidence of
      dementia and all-cause mortality among patients with dementia.
AB  - This study investigated the effects of the presence of type 2 diabetes mellitus
      (T2D) and/or chronic liver disease (CLD) on the incidence and prognosis of
      dementia during a 10-year period in Korea using a nationwide population-based
      dataset from the Korea National Health Insurance Service.To assess the impact of
      T2D and CLD on the incidence of dementia, we included subjects aged >=60 years
      without dementia, T2D, and CLD from 2003 to 2005. We created another cohort for
      evaluating the all-cause mortality in subjects with dementia between 2003 and
      2005. The participants were categorized into 4 groups: control (neither CLD nor
      T2D), CLD-only, T2D-only, and T2D-and-CLD groups, and they were followed up until
      2013.The incidence of dementia was higher in the T2D-only group than in the
      control and CLD-only groups (2.78 vs. 2.04 and 2.00 per 1000 person-years). After
      adjustment for age, gender, and comorbid conditions, both T2D and CLD increased
      the risk of any type of dementia; however, the impact of CLD alone was much lower
      [hazard ratio (HR) 1.07, 95% confidence interval (CI): 1.06-1.08] than that of
      T2D alone (HR 1.27, 95% CI: 1.27-1.28). The risk of dementia did not
      significantly change in patients with the co-occurrence of T2D and CLD compared
      to those with T2D alone. The all-cause mortality rate was the lowest in the
      control group (2.59 per 1000 person-years) and the highest in the T2D-and-CLD
      group (3.77 per 1000 person-years). Presence of T2D or CLD alone was associated
      with higher mortality (HR 1.46 and HR 1.21, respectively) compared with in the
      absence of both the diseases. Furthermore, the presence of both the diseases
      further significantly increased the mortality rate compared to the presence of
      each disease alone (HR 1.67, 95% CI: 1.65-1.69).In conclusion, this study found
      that the incidence of dementia was much higher in patients with T2D. CLD was
      associated with a modest increase in risk of dementia; however, there was no
      additive effect with T2D. In the population with dementia, however, the presence
      of CLD was associated with high mortality in patients with or without T2D.

PMID- 29381971
TI  - Isolated intracranial Rosai-Dorfman disease mimicking petroclival meningioma in a
      child: Case report and review of the literature.
AB  - RATIONALE: Rosai -Dorfman disease (RDD) is a rare, idiopathic, and non-neoplastic
      histioproliferative disease with distinctive entity of unknown etiology. Central
      nervous system (CNS) RDD is uncommon, hence, isolated intracranial RDD is
      extremely rare. So far only 6 cases of CNS RDD with the lesions originating from
      petroclival region have been reported. We present a case of isolated intracranial
      RDD mimicking petroclival meningioma. PATIENT CONCERNS: A 14-year-old girl was
      admitted at our hospital with a 3-month history of dizziness, slowly progressing
      headache, and 2-month history of instability in walking. Cranial nerve deficits,
      including left facial paralysis, left facial numbness and left hearing loss, were
      evident on examination. DIAGNOSES: Initial diagnosis of petroclival meningioma
      was made according to preoperative magnetic resonance imaging. INTERVENTIONS: The
      lesion was resected subtotally and pathology confirmed RDD. The patient received
      gamma-knife treatment for the residual lesion. OUTCOMES: The patient recovered
      well and the residual lesion significantly retrogressed on follow-up images.
      LESSONS: Preoperative diagnosis of petroclival RDD is full of challenges.
      Although surgical resection of lesions is an effective treatment option, total
      resection is not highly recommended because the surgery-related defect must be
      minimal. Patient with residual lesion can be put on steroid therapy and/or
      radiotherapy, especially for IgG4 positive subset of RDD.

PMID- 29381972
TI  - Outcomes of iontophoretic corneal collagen crosslinking in keratoconic eyes with
      very thin corneas.
AB  - The purpose of this retrospective study was to report the results of
      iontophoretic corneal collagen crosslinking (I-CXL) with riboflavin and
      ultraviolet A irradiation in patients affected by keratoconus, each with thinnest
      pachymetry values of <400 MU (with epithelium) and not treatable using standard
      epithelium-off technique.Fifteen eyes of 15 patients affected by progressive
      keratoconus and with thinnest pachymetry values <400 MU underwent I-CXL. The
      uncorrected (UDVA) and corrected (CDVA) distance visual acuity, maximum and
      minimum keratometry (K max and K min) readings, corneal thickness at the thinnest
      point (CTTP), endothelial cell density (ECD), and intraocular pressure (IOP) were
      assessed before I-CXL, at 1, 3, 6, and 12 months postoperatively.The mean UDVA
      and CDVA significantly increased 12 months after I-CXL (P = .002 for both
      comparisons). The K max readings significantly decreased at 6 and 12 months
      postoperatively (P = .04 and P = .02, respectively). The mean CTTP improved at
      the end of the follow-up (P = .008). ECD was unchanged. No side effects or damage
      to the limbal region was observed during the follow-up period.I-CXL has been
      proved to be effective in halting keratoconus progression in eyes with very thin
      corneas, with no side effects during the follow-up period. This procedure could
      be used in patients with more advanced keratoconus.

PMID- 29381973
TI  - Mucinous tumor arising in a giant sacrococcygeal teratoma: A rare case report.
AB  - RATIONALE: Teratomas, which most frequently affect adult females, are the most
      common type of germ cell tumor, it always comprises derivatives of at least 2
      germ layers. The most common site of primary teratomas is the ovary.
      Sacrococcygeal teratomas (SCTs), which are exceedingly rare in adults, are
      generally found in newborns or children. PATIENT CONCERNS: A 39-year-old woman
      presented to our clinic with a 1-year history of gradually aggravated difficulty
      in micturition and defecation, and a tumor in her right buttock present since
      birth. Appropriate preoperative examinations showed a large (15.6 cm * 12.2 cm *
      30.0 cm) multicystic SCT. DIAGNOSES: Histologic examination confirmed a mucinous
      tumor arising in a giant SCT. INTERVENTIONS: Abdominoperineal rectal resection
      was performed. OUTCOMES: The patient recovered well and was discharged on day 33
      of admission. LESSONS: We report the first case of a mucinous tumor arising in an
      SCT, in which the teratoma presented mature tissue elements derived only from the
      endodermal germ layer (keratinous debris).

PMID- 29381974
TI  - Stroke risks and patterns of warfarin therapy among atrial fibrillation patients
      post radiofrequency ablation: A real-world experience.
AB  - We assessed the thromboembolic risks of atrial fibrillation (AF) patients who had
      undergone radiofrequency ablation (RFA) using the CHADS2-VASc risk scoring system
      and further investigated the patterns of warfarin use for thromboprophylaxis
      according to patient thromboembolic risk scores.In this study, we analyzed the
      stroke risks of patients who had undergone RFA for AF at our hospital between
      March 2014 and June 2016 using the CHADS2, CHADS2-VASc, and Hypertension,
      Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile
      international normalized ratio, Elderly (> 65 years) (HAS-BLED) scoring systems.
      We retrieved medications, co-morbidities, and initial warfarin dosage data. The
      primary outcome was the percentage of patients initiated with warfarin therapy
      for stroke prophylaxis in AF who had a CHADS2-VASc score of 0.Totally, 309
      patients were initiated with warfarin therapy for stroke prophylaxis in AF post
      RFA. The baseline warfarin dosage was 2.76 +/- 0.61 mg. The baseline CHADS2-VASC
      score was 2.93 +/- 1.96 and 40 (12.95%) had a CHADS2-VASC score of 0, 42 (13.6%)
      had a CHADS2-VASCscore of 1, and 227 (73.5%) had a CHADS2-VASC score >=2. The
      baseline CHADS2 score was 2.17 +/- 1.55 and 48 (15.5%) had a CHADS2 score of 0,
      68 (22.0%) had a CHADS2 score of 1, and 193 (62.5%) had a CHADS2 score >=2. The
      baseline HAS-BLED score was 1.25 +/- 0.91 and 69 (22.3%) had a HAS-BLED score of
      0, 121 (39.2%) had a HAS-BLED score of 1, and 119 (38.5%) had a HAS-BLED score
      >=2. Patients aged <65 years or 65 years, male and female patients, patients with
      or without hypertension, coronary heart disease, or diabetes mellitus, and
      patients with or without previous stroke/transient ischemic attack differed
      significantly in stroke risks by CHADS2-VASC, CHADS2, and HAS-BLED scores for
      stroke risks. Patients with different baseline international normalized ratio
      differed significantly in CHADS2-VASC scores. Furthermore, angiotensin-converting
      enzyme inhibitors or angiotensin receptor blockers and statins were of
      statistical significance for stroke risks.The majority of AF patients post-RFAs
      was of high stroke risk and received warfarin thromboprophylaxis in accordance
      with national guidelines. Our findings suggest that low and intermediate stroke
      risk patients should be evaluated for stroke risks and risk factors so that
      tailored warfarin thromboprophylaxis therapy can be given and inappropriate use
      of warfarin in AF patients can be avoided.

PMID- 29381975
TI  - Comparison of intraoperative basal fluid requirements in distal pancreatectomy:
      Laparotomy vs. laparoscopy: A retrospective cohort study.
AB  - There has been recent progress in intraoperative fluid therapy. However, little
      is known about intraoperative fluid therapy in laparoscopic surgery. The purpose
      of this study is to determine whether there are differences in the basal fluid
      requirements during surgery between laparotomy and laparoscopic distal
      pancreatectomy.This retrospective cohort study analyzed the electronic medical
      records of 253 patients who underwent distal pancreatectomy via either laparotomy
      (73 patients) or laparoscopy (180 patients) between June 2006 and March 2016. The
      volume of intraoperative fluid administered, postoperative complications, length
      of hospital stay, and readmission rate were evaluated. The total volume of fluids
      was calculated as the sum of the volume of crystalloid plus the volume of colloid
      multiplied by 1.5 or 2.0.Patients who had laparotomy were older and had higher
      American Society of Anesthesiologists classes. Anesthesia time was longer and
      estimated blood loss was larger in laparotomy. More colloid (1.8 mL/kg per h vs.
      1.2 mL/kg per h, P < .001) and more total calculated fluid (1.5 times: 11.7 mL/kg
      per h vs. 10.6 mL/kg per h, P = .002; 2.0 times: 12.6 mL/kg per h vs. 11.2 mL/kg
      per h, P = .001) were infused in laparotomy. Crystalloid (9.0 mL/kg per h vs. 8.9
      mL/kg per h, P = .203) did not show significant difference. Postoperative
      complications were more frequent (63% vs. 45%, P = .008), the hospital stay was
      longer (18 days vs. 13.4 days, P < .001), and readmission rate was higher (15%
      vs. 5.6%, P = .02) in laparotomy. By logistic regression analysis, we could find
      that operation type (laparotomy vs. laparoscopy, odds ratio 1.900, 95% confidence
      interval 1.072-3.368) and operation time (P = .004) had effect on
      complications.In patients undergoing distal pancreatectomy, basal fluid
      requirements were larger in laparotomy compared with laparoscopy. Operation time
      and estimated blood loss had effects on fluid administration. Postoperative
      complications were more frequent in laparotomy but we could not find
      relationships with infused colloid or total calculated fluid volumes. Operation
      type (laparotomy vs. laparoscopy) and operation time were the only related
      factors to postoperative complications.

PMID- 29381976
TI  - Thyroid-associated orbitopathy in patients with thyroid carcinoma: A case report
      of 5 cases.
AB  - RATIONALE: Thyroid-associated orbitopathy (TAO) is most often seen in patients
      with autoimmune thyroid disease. Data about TAO occurred in patients with thyroid
      carcinoma are rare. We give a report of 5 patients to present the clinical
      characteristics, treatment, and prognosis of this type of case. PATIENT CONCERNS:
      Five thyroid carcinoma patients presented with orbitopathy. Among them, two
      patients (patient 1 and 4) were hyperthyroid and TSH receptor antibody (TRAb)
      positive, two patients (patient 3 and 5) were euthyroid and displayed slightly
      elevated TRAb titres, one patient (patient 2) was euthyroid and TRAb negative.
      DIAGNOSES: They were diagnosed as thyroid carcinoma and TAO. INTERVENTIONS:
      Patient 1 underwent total thyroidectomy, intravenous glucocorticoids (GCs)
      therapy, orbital decompression surgery and oral GCs therapy. Patient 2 and 3 only
      received total thyroidectomy. Patient 4 received sub-total thyroidectomy and oral
      GCs therapy. patient 5 didn't received thyroidectomy and underwent intravenous
      GCs therapy for 2 courses. OUTCOMES: Patient 1,2,3 showed an improvement of TAO
      at the final follow-up. Patient 4,5 showed no improvement of TAO at the final
      follow-up. LESSONS: When TAO present in patients with thyroid nodules, the
      possibility of thyroid carcinoma should be considered, and the nature of these
      nodules should be carefully evaluated. In some patients with thyroid carcinoma
      and TAO, the remission of TAO can be seen post total thyroidectomy. But for other
      patients, besides thyroidectomy, an adequate dose and course of intravenous GCs
      treatment and even ocular surgery are also needed.

PMID- 29381977
TI  - Bleeding from isolated gastric varices as complication of a mucinous cystic
      neoplasm of the pancreas: A case report.
AB  - INTRODUCTION: Bleeding from isolated gastric varices, though uncommon, may be
      life threatening and may occur as a consequence of splenic vein thrombosis by
      tumoral compression and subsequent left-sided portal hypertension. CASE OVERVIEW:
      We report the case of a 37-year old woman, previously diagnosed with a benign
      pancreatic cyst, who presented with severe gastric variceal bleeding. DIAGNOSIS,
      THERAPEUTICS INTERVENTIONS, AND OUTCOMES: Abdominal ultrasound (US) and computed
      tomography (CT) revealed enlargement and changed morphology of the cystic tumor
      located on the body of the pancreas. Left-sided portal hypertension was disclosed
      resulting from splenic vein occlusion. Salvage left spleno-pancreatectomy with
      lymphadenectomy was undertaken with an excellent postoperative outcome.
      Histological analysis established the diagnosis of mucinous cystic neoplasm with
      foci of adenocarcinoma. CONCLUSION: Surgical treatment proved to be the election
      one, leading to a steady hemostasis, removal of the lesion, positive diagnosis,
      and resolution of the varices. Imaging follow-up of pancreatic cyst should also
      assess vascular patency to identify the patient at risk for gastric bleeding and
      to select patients who benefits from surgical resection.

PMID- 29381978
TI  - Cholecystectomy with gallbladder bed cautery might be sufficient for T1bN0M0
      neuroendocrine carcinoma of gallbladders: Cases report and literature review.
AB  - INTRODUCTION: Neuroendocrine carcinoma was a rare kind tumor in gallbladders. So
      far, there is no consensus of treatment of the gallbladder neuroendocrine
      carcinoma. CASE PRESENTATION: Three patients, 1 male and 2 females, were admitted
      in our hospital because of right upper quadrant pain. No one complained fever,
      jaundice, weight loss, or carcinoid syndrome-related symptoms such as diarrhea,
      flushing, edema, and wheezing. The MRI detected the broad base of gallbladder
      tumors. However, they refused any radical surgery. We performed a laparoscopic
      cholecystectomy with gallbladder bed cautery. The pathology results showed that 2
      cases were mixed neuroendocrine carcinoma (NECs), and 1 case was a simple NEC.
      Chromogranin A and synaptophysin were positive in all cases. The pathological TNM
      stages of all patients were in the T1bN0M0 stage. The range of Ki-67 was from 40%
      to 80%. During the at least 26 months' follow-up, there is no case with the
      recurrence of the carcinoma without any chemotherapy or radiotherapy.
      CONCLUSIONS: Cholecystectomy with gallbladder bed cautery might be enough for
      treatment of T1bN0M0 gallbladder neuroendocrine carcinoma.

PMID- 29381979
TI  - Multiple arterial thromboses due to cystic medial degeneration Erdheim-Gsell: A
      case report.
AB  - RATIONALE: Cystic medial degeneration Erdheim-Gsell is a vascular pathology
      mainly of the large vessels, which is mostly associated with Marfan syndrome or
      Ehlers-Danlos syndrome. The clinical findings of this entity are aneurysms of the
      aorta or large peripheral arteries which usually present in an acute setting due
      to rupture of an aneurysm. PATIENT CONCERNS: We present a case of a 43-year-old
      Caucasian male with histologically proven cystic medial degeneration of the lower
      limb vessels mimicking peripheral artery occlusive disease. Despite antiplatelet
      and anticoagulant treatment, the patient suffered multiple vascular stenosis and
      occlusions. DIAGNOSES: Multiple arterial stenoses and thromboses leading to
      peripheral artery occlusive disease caused by cystic medial degeneration Erdheim
      Gsell. INTERVENTIONS: Multiple surgical and endovascular interventions including
      bypass graft and intra-arterial thrombolysis as well as oral antiplatelet and
      anticoagulant therapy. OUTCOME: Despite dual antiplatelet therapy, anticoagulant
      therapy with rivaroxaban and multiple surgical and endovascular interventions,
      the patient developed recurrent arterial thromboses. The patient did not suffer
      further thrombotic events since clopidogrel and phenprocoumon were administered.
      LESSONS: Clinical presentation of cystic medial degeneration Erdheim-Gsell
      mimicking peripheral artery occlusive disease is very unusual. Due to the fragile
      vessel wall, patients with cystic medial degeneration might have a higher risk to
      develop arterial thromboses, even under antiplatelet therapy or anticoagulant
      treatment.

PMID- 29381980
TI  - Circulating D-dimer level correlates with disease characteristics in
      hepatoblastoma patients.
AB  - OBJECTIVES: Hepatoblastoma (HB) is the most common pediatric liver malignancy,
      typically affecting children within the first 4 years of life. However, only a
      few validated blood biomarkers are used in clinical evaluation. The current study
      explored the clinical application and significance of D-dimer levels in patients
      with HB. METHOD: Forty-four patients with HB were included in this retrospective
      study. D-dimer and plasma fibrinogen levels were examined, and their correlation
      with other clinical features was analyzed. D-dimer and plasma fibrinogen levels
      were examined between HB and other benign hepatic tumors. RESULTS: D-dimer levels
      were significantly associated with high-risk HB features, such as advanced stage
      and high alpha-fetoprotein (AFP) levels. Higher D-dimer levels were observed in
      stage 4 patients compared with stage 1/2/3 patients (P = .028). Higher D-dimer
      levels were also observed in patients with higher AFP levels before chemotherapy
      compared with patients with lower AFP levels after chemotherapy (P< 0.001). In
      addition, higher D-dimer levels were observed in HB compared with other benign
      hepatic tumors such as hepatic hemangioma and hepatocellular adenoma (P = .012).
      No significant difference in D-dimer levels was found between sex (P = .503) and
      age (>=12 vs <12 months, P = .424). There was no significant difference in plasma
      fibrinogen levels between sex or age and high-risk HB features, such as advanced
      stage and high AFP levels. CONCLUSIONS: Elevated D-dimer levels could be a useful
      determinant biomarker for high-risk features in patients with HB. This finding
      also supports the clinical application of D-dimer in HB.

PMID- 29381981
TI  - The effectiveness of acupuncture for chronic pain with depression: A systematic
      review protocol.
AB  - BACKGROUND: Chronic pain is a major public health problem and 30% to 45% of
      sufferers experience severe depression. Acupuncture is often used to treat both
      depression and a range of pain disorders. We aim to conduct a systematic review
      of randomized controlled trials (RCTs) to evaluate the efficacy of acupuncture
      for patients experiencing chronic pain with depression. METHODS: To identify
      relevant RCTs, the following databases will be searched electronically from their
      inception to July 1, 2017: PubMed, MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials, the Allied and Complementary Medicine Database, the Cumulative
      Index to Nursing and Allied Health Literature, Chinese medical databases, and
      others. Manual retrieval will also be conducted. RCTs that evaluated acupuncture
      as the sole or adjunct treatment for patients with chronic pain and depression
      will be included. The primary outcomes will be based on a visual analog pain
      measurement scale and the Hamilton Depression Scale. The secondary outcomes will
      include scores on a numerical rating scale, verbal rating scale, and the Hospital
      Anxiety and Depression Scale. The study selection, data extraction, and study
      quality evaluation will be performed independently by 2 researchers. If the data
      permit, meta-analysis will be performed using RevMan V5.3 statistical software.
      If the data are not appropriate for meta-analysis, descriptive analysis or
      subgroup analysis will be conducted. The methodological quality of the included
      trials will be assessed using the Cochrane risk-of-bias criteria and the
      Standards for Reporting Interventions in Controlled Trials of Acupuncture
      checklist. RESULTS: This study will provide a high-quality synthesis of current
      evidence of acupuncture for chronic pain with depression from several scales
      including visual analog pain measurement scale, the Hamilton Depression Scale, a
      numerical rating scale, verbal rating scale and the Hospital Anxiety and
      Depression Scale. CONCLUSION: The conclusion of our study will provide updated
      evidence to judge whether acupuncture is an effective intervention for patients
      suffered from chronic pain with depression.

PMID- 29381982
TI  - Metabolic acidosis of chronic kidney disease and subclinical cardiovascular
      disease markers: Friend or foe?
AB  - The effect of chronic metabolic acidosis (MA) on cardiovascular disease (CVD) in
      the setting of chronic kidney disease (CKD) is largely unknown. Therefore, we
      aimed to study this relationship in nondialysis CKD patients.This cross
      sectional, single-center study prospectively enrolled 95 clinically stable CKD
      patients (median age 61 (58, 65) years, 60% male, median eGFR 27 (22, 32)
      mL/min). Data on CKD etiology, CVD history, CVD traditional, and nontraditional
      risk factors were obtained. Also, markers of subclinical CVD were assessed:
      intima-media thickness (IMT), abdominal aortic calcifications (Kauppila score
      AACs), cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), ejection
      fraction, and interventricular septum thickness. Using the serum bicarbonate
      cutoff value of 22 mEq/L, comparisons between MA (<22 mEq/L; 43 patients) and non
      MA (>=22 mEq/L; 52 patients) groups were performed.Vascular (40%),
      tubulointerstitial (24%), and glomerular (22%) nephropathies were the main causes
      of CKD. Twenty-three percent of patients had diabetes mellitus, but only 5% were
      considered to have diabetic nephropathy. Patients with chronic MA had lower eGFR
      (P < .01), higher iPTH (P = .01), higher serum phosphate (P < .01), and increased
      serum cholesterol (P = .04) and triglycerides (P = .01).Higher ABI (P = .04),
      lower IMT (P = .03), CAVI (P = .05), and AACs (P = .03) were found in patients
      with chronic MA.Separate binomial logistic regression models were performed using
      ABI (cutoff 0.9), CAVI (cutoff 9), IMT (cutoff 0.1 cm), and AACs (cutoff 1) as
      dependent variables. MA was used as independent variable and adjustments were
      made for iPTH, serum phosphate, eGFR, proteinuria, cholesterol, triglycerides,
      CVD score. The absence of MA was retained as an independent predictor only for
      the presence of AACs.In conclusion, the present study shows a potential
      advantageous effect of MA on vascular calcifications in predialysis CKD patients.
      Thus, a guideline relaxation of the serum bicarbonate target might prove to be
      beneficial in CKD patients at high risk of vascular calcifications. However, one
      should always consider the negative effects of MA. Therefore, additional research
      is warranted before any clear clinical recommendation.

PMID- 29381983
TI  - Preoperative intravenous glucocorticoids can decrease acute pain and
      postoperative nausea and vomiting after total hip arthroplasty: A PRISMA
      compliant meta-analysis.
AB  - BACKGROUND: A systematic review and meta-analysis of published randomized
      controlled trials (RCTs) were performed to assess the efficacy and safety of
      preoperative intravenous glucocorticoids versus controls for the prevention of
      postoperative acute pain and postoperative nausea and vomiting (PONV) after
      primary total hip arthroplasty (THA). METHODS: A computer literature search of
      electronic databases, including PubMed, Embase, the Cochrane Central Register of
      Controlled Trials (CENTRAL), Web of Science, China National Knowledge
      Infrastructure (CNKI), and China Wanfang database, was conducted to identify the
      relevant RCTs comparing preoperative intravenous glucocorticoids versus placebos
      for reducing acute pain and PONV in THA patients. The primary outcomes included
      the use of the visual analog scale (VAS) with rest or mobilization at 6, 24, 48,
      and 72 hours and the occurrence of PONV. The secondary outcome was total morphine
      consumption. We calculated the risk ratio (RR) with a 95% confidence interval
      (95% CI) for dichotomous outcomes, and the weighted mean difference (WMD) with a
      95% CI for continuous outcomes. RESULTS: Pooled data from 7 RCTs (411 THAs)
      favored preoperative intravenous glucocorticoids against acute pain intensity at
      4, 24, and 48 hours (P < .05). There was no significant difference between the
      VAS with rest or mobilization at 72 hours (P > .05). Subsequently, preoperative
      intravenous glucocorticoids provided a total morphine-sparing effect of 9.36 mg
      (WMD = -9.36, 95% CI = -12.33 to -6.38, P = .000). In addition, preoperative
      intravenous glucocorticoids were associated with a significant reduction of the
      occurrence of PONV (RR = 0.41, 95% CI = 0.30-0.57, P = .000). CONCLUSION:
      Intravenous glucocorticoids can decrease early pain intensity and PONV after THA.
      However, the low number of studies and variation in dosing regimens limits the
      evidence for its use. Thus, more high-quality RCTs are still needed to identify
      the optimal drug and the safety of intravenous glucocorticoids.

PMID- 29381984
TI  - Periprosthetic bone remodeling of short cementless femoral stems in primary total
      hip arthroplasty: A systematic review and meta-analysis of randomized-controlled
      trials.
AB  - BACKGROUND: Short-stem total hip arthroplasty (SHA) has been increasingly used in
      the treatment of hip arthroplasty. However, it is unclear whether there is a
      superiority of SHA in periprosthetic bone remodeling over standard stem total hip
      arthroplasty (THA). This meta-analysis of randomized-controlled trials (RCTs)
      compared the periprosthetic bone remodeling after SHA and THA. METHODS: PubMed
      and Embase were screened for relevant publications up to May 2017. RCTs that
      compared periprosthetic bone remodeling with bone mineral density (BMD) changes
      between SHA and THA were included. Meta-analysis was conducted to calculate
      weighted mean differences (WMDs) and 95% confidence intervals (CIs) using Stata
      version 12.0. Quality appraisal was performed by 2 independent reviewers using
      RevMan 5.3 software and Grades of Recommendation Assessment, Development, and
      Evaluation criteria. RESULTS: Seven studies involving 910 patients and 5 SHA
      designs (Proxima, Fitmore, Microplasty short, Unique custom, and Omnifit-HA 1017)
      were included for meta-analysis. The pooled data showed no significant
      differences in the percentage BMD changes in all Gruen zones, with Gruen zone 1
      [mean difference (MD) = 11.33, 95% CI, -1.67 to 24.33; P = .09] and Gruen zone 7
      (MD = 8.46, 95% CI, -1.73 to 18.65; P = .10). Subgroup analysis of short SHA
      stems with lateral flare showed a significant less percentage BMD changes
      compared with standard THA in Gruen zone 1 (MD = 27.57, 95% CI, 18.03-37.12; P <
      .0001) and Gruen zone 7 (MD = 18.54, 95% CI, 8.27-28.81; P < .0001). CONCLUSION:
      The study shows moderate-quality evidence that periprosthetic bone remodeling
      around the analyzed SHA stems was similar to standard THA stems. However, short
      SHA stems with lateral flare revealed a moderate- to low-quality evidence for
      superiority over the standard THA and highlighted the importance of the different
      SHA designs. Besides, it has to be noticed that despite a similar pattern of
      periprosthetic bone remodeling, the femoral length where periprosthetic bone
      remodeling occurs is clearly shorter in SHA. Due to the moderate- to low-quality
      evidence and the limited stem designs analyzed, the further large-scale
      multicenter RCTs including the most recent SHA designs are required. However, the
      current findings should be considered by surgeons for counseling patients
      regarding total hip replacement.

PMID- 29381985
TI  - Sudden cardiac death owing to arrhythmogenic right ventricular cardiomyopathy:
      Two case reports and systematic literature review.
AB  - BACKGROUND AND OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC)
      is increasingly recognized in forensic practice with controversial diagnosis.
      Here we described the epidemiological characteristics and reported the
      pathogenetic mechanism, diagnostic challenges, and forensic implications of
      Chinese ARVC autopsy cases. METHODS: Two cases of sudden cardiac death owing to
      ARVC were reported. Retrospective analysis were performed on such 2 cases and 45
      cases of separate ARVC complete autopsy case reports through Chinese literature
      databases in the last 30 years. RESULTS: There were 27 males and 20 females, and
      the mean age at death was 35 years. Sudden cardiac death was the first
      manifestation observed in most patients, with no previous family and medical
      history. Exercise, acute stress, increased cardiac workload, and ethanol are
      frequently involved. The mean heart weight was 393 g (range, 240-590 g), and 10
      cases had relative heart hypertrophy. Microscopic abnormalities included
      replacement of myocardium by adipose infiltration in 68.09% cases and
      fibroadipose in 31.91% cases; 80.85% cases were restricted to the right ventricle
      (RV), whereas biventricular subtype was seen in the remaining 19.15% cases. The
      preliminary quantitative histology showed 60.7% of fat tissues, 12.1% of
      fibrosis, and 27.2% residual myocytes in RV. Inflammatory cell infiltration was
      found in 25.53% cases, but myocyte necrosis was found in only 1 case. In 10.64%
      of cases, cardiac conduction was infiltrated by fibrosis, adipose, or both.
      CONCLUSION: In this review, the most characteristic and distinct histopathologic
      features that are diagnostic or highly suggestive of ARVC for forensic
      pathologists were identified. Combining gross and histological examinations with
      postmortem genetic analysis is recommended for identifying ARVC.

PMID- 29381986
TI  - ST segment elevation associated with hydrochloric acid ingestion: A case report.
AB  - RATIONALE: Electrocardiography (ECG) was used to diagnose acute coronary
      syndrome, but many other diseases may also result in ST segment change. We report
      one case of ingested hydrochloric acid present with ST segment elevation in the
      ECG. However, subsequent coronary angiography did not reveal significant coronary
      occlusion. PATIENT CONCERNS: An 83-year-old female was transferred to our
      emergency department (ED) from the branch hospital due to ingestion of toilet
      bowl cleaner containing 9.5% hydrochloric acid. She complained about chest pain
      and 12-lead ECG showed ST segment elevation at lead II, III, and aVF. The blood
      examinations revealed elevation of aspartate transaminase (69 IU/L),
      thrombocytopenia (62,000/MUL), and acidosis (pH 7.311, pCO2 27 mm Hg, HCO3 13.3
      mmol/L). Creatine kinase-MB and troponin I did not elevate then. DIAGNOSES: After
      transferred to our ED, coronary angiography was done within 1 hour. Angiography
      showed 60% stenosis in the segment 7 of left anterior descending coronary artery
      and 30% nonsignificant stenosis in the segment 2 of right coronary artery, with
      no apical ballooning. No significant lesion consistent with ST segment elevation
      myocardial infarction was found. INTERVENTIONS: Conservative treatment was
      chosen. OUTCOMES: Bradycardia was followed by cardiac arrest that developed 4
      hours later. Cardiopulmonary resuscitation was applied and the patient became
      shock status after return of spontaneous circulation. The patient was admitted to
      the intensive care unit and expired on next day. LESSONS: Patients of ingested
      hydrochloric acid present with ST segment elevation in the ECG may not indicate
      coronary artery disease. This ECG finding may be a poor prognostic index in such
      patients.

PMID- 29381987
TI  - A case report and literature review of barium sulphate aspiration during upper
      gastrointestinal examination.
AB  - RATIONALE: Even though barium sulphate aspiration during upper gastrointestinal
      examination is a well-known phenomenon, complication such as long-term lung
      injury and death may still occur. This may depend upon the concentration, amount,
      anatomy, or certain predisposing factors. PATIENT CONCERNS: A 47-year-old woman
      who had a barium swallow to screen for foreign body in esophagus. DIAGNOSES:
      Chest radiographs demonstrated massive barium sulphate depositions in her trachea
      and inferior lobe of right lung. INTERVENTIONS: A chest x-ray was done that
      revealed massive barium sulphate depositions in her trachea and lower lobe of
      right lung. As the patient did not have further complaints, she requested a
      transfer to West China Hospital of Sichuan University, the hospital being near
      her residence, for further treatment. She eventually recovered and was discharged
      after 1 week. OUTCOMES: There were 23 articles (22 English and 1 Chinese with 17
      men and 11 women) included in the study. The risk factors of barium sulphate
      aspiration are dysphagia (10/28, 35.71%) followed by esophageal obstruction
      caused by tumor (5/28, 17.86%) and foreign body in esophagus (3/28, 10.71%).
      Infants (5/28, 17.86%) are also one of the high-risk population. Both the lungs
      were affected in most of the patients (21/28, 75%). Majority of the presentation
      in patients (21/28, 75%) were dyspnea, hypoxemia, acute respiratory distress
      syndrome (ARDS), or respiratory failure. Few patients (7/28, 25%) showed no
      symptoms or mild symptoms such as cough and fever. Barium sulphate aspiration can
      be life-threatening with a high risk of death (nearly 40%). LESSONS: When
      performing an upper gastrointestinal examination with barium sulphate, careful
      consideration of concentration and amount of barium sulphate and that of risk
      factors should be undertaken so as to avoid life-threatening aspiration.

PMID- 29381988
TI  - Efficacy of acupuncture on menstrual frequency in women with polycystic ovary
      syndrome: Protocol for a randomized, controlled trial.
AB  - BACKGROUND: Acupuncture may improve the menstrual frequency of women with
      polycystic ovary syndrome (PCOS). However, more sufficient data are needed to
      improve the efficacy of acupuncture. METHODS: A total of 172 participants
      diagnosed with PCOS would be randomly assigned to either the acupuncture group or
      sham-acupuncture group, at a ratio of 1:1. Participants in both groups will
      receive treatment for 12 weeks, 3 times a week. The primary outcome will be the
      proportion of participants with at least a 50% increase from baseline in the
      monthly menstrual frequency from baseline after 12 weeks intervention, while
      secondary outcomes will be the difference in anthropometrics, serum hormone
      level, ovarian morphology, anxiety and depression, and quality of life from
      baseline to after 12 weeks intervention and to 12 weeks postintervention follow
      up between groups. DISCUSSION: The aim of this study is to evaluate the efficacy
      and safety of acupuncture for improving menstrual frequency and other symptoms of
      patients with PCOS. The limitation of this trial is that it would be difficult to
      blind the acupuncturists. In addition, these findings may not be suitable for
      women with PCOS who are seeking pregnancy.

PMID- 29381989
TI  - Application of gluteus maximus fasciocutaneous V-Y advancement flap combined with
      resection in sacrococcygeal pressure ulcers: A CONSORT-compliant article.
AB  - BACKGROUND: Traditional gluteus maximus myocutaneous flaps have generally been
      used to fill tissue defects after resection of sacrococcygeal pressure ulcers.
      However, postoperative complications were gradually revealed as increasing
      operations were performed. This study aimed to introduce the innovative
      application of gluteus maximus fasciocutaneous V-Y advancement flaps for
      repairing tissue defects and to comparatively analyze the differences between the
      innovative and traditional flaps. METHODS: A total of 32 cases were included in
      this study. All the PU lesions were removed by resection. Sixteen cases used the
      gluteus maximus myocutaneous flaps, and the remaining 16 cases used gluteus
      maximus fasciocutaneous V-Y advancement flaps to fill the tissue defects after
      surgery. Comparative analysis between the gluteus maximus myocutaneous flaps and
      gluteus maximus fasciocutaneous V-Y advancement flaps was used to evaluate the 2
      flaps based on the mean operating time, postoperative infection, paresthesia,
      appearance of flaps, and recurrence. RESULTS: The gluteus maximus fasciocutaneous
      V-Y advancement flaps required a reduced operating time and a more simple
      operation compared with the gluteus maximus myocutaneous flaps. Although the
      infectious risk of the gluteus maximus fasciocutaneous V-Y advancement flaps was
      reduced compared with the gluteus maximus myocutaneous flaps, the gluteus maximus
      myocutaneous flaps have a better appearance compared with the gluteus maximus
      fasciocutaneous V-Y advancement flaps. Most importantly, no flap necrosis was
      noted, and the recurrence rate during follow-up was reduced in cases using the
      gluteus maximus fasciocutaneous V-Y advancement flaps. CONCLUSION: The combined
      application of gluteus maximus fasciocutaneous V-Y advancement flaps with
      surgical resection can reduce the postoperative complications and aid in the
      treatment of sacrococcygeal pressure ulcers.

PMID- 29381990
TI  - A case study of Ramsay Hunt Syndrome in conjunction with cranial polyneuritis.
AB  - RATIONALE: Ramsay Hunt syndrome in conjunction with cranial polyneuritis is not
      extensively documented, and is very easily misdiagnosed. PATIENT CONCERNS: A case
      of a 53-year-old male with Ramsay Hunt syndrome in conjunction with cranial
      polyneuritis is presented with early symptoms of vertigo, cephalalgia, and facial
      palsy, followed by zoster oticus 10 days later. DIAGNOSES: Diagnosis was
      challenging as this condition presents with multiple neuropathies, and attempting
      to diagnose based on clinical symptoms was often misleading. Polymerase chain
      reaction can be used to test for presence of the virus in the cerebrospinal
      fluid, followed by targeted drug therapy. INTERVENTIONS: Acupuncture, in
      conjunction with fire cupping, bloodletting around the afflicted region on the
      face, as well as oral consumption of herbal medicine and vitamins for nerve
      nourishment was given to treat this disease. OUTCOMES: Due to misdiagnosis
      resulting in delayed treatment, peripheral facial paralysis was left as the main
      sequelae, while other symptoms responded quickly to treatment. After a 6-month
      follow-up, facial palsy was still present. LESSONS: Considering that targeted
      antiviral therapy can be used to increase the effectiveness of treatment, early
      diagnosis, and timely use of medication is critical.

PMID- 29381991
TI  - RNA sequencing uncovers the key microRNAs potentially contributing to sudden
      sensorineural hearing loss.
AB  - This study aimed to identify miRNAs that may contribute to the pathogenesis of
      sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was
      extracted from SSNHL patients and healthy volunteers, respectively. Sequencing
      was performed on HiSeq4000 platform. After filtering, clean reads were mapped to
      the human reference genome hg19. Differential expression analysis of miRNAs
      between the SSNHL samples and the normal samples was performed using DEseq to
      identify differentially expressed microRNAs (DEMs). The target genes of the DEMs
      were predicted using the online tool miRWalk, which were then mapped to DAVID
      (https://david.ncifcrf.gov/) for functional annotation based on GO database and
      for pathway enrichment analysis based on KEGG. Finally, a miRNA-target-protein
      protein interaction (PPIs) network was constructed using the DEMs and their
      target genes with interaction.Differential expression analysis reveals 24 DEMs
      between the SSNHL group and control group. A total of 1083 target genes were
      predicted. GO functional annotation analysis reveals that the target genes in the
      top 10 terms are mainly related to the development of salivary glands,
      neurotransmission, dendritic development, and other processes. KEGG pathway
      enrichment analysis reveals that the target genes were functionally enriched in
      pathways arachidonic acid metabolism, complement and coagulation cascades,
      linoleic acid metabolism, and MAPK signaling pathway. In the miRNA-target-PPI
      network, hsa-miR-34a/548n/15a/143/23a/210/1255a/18b/ /1180/99b had the most
      target genes; genes YWHAG, GSK3B, CDC42, NR3C1, LCK, UNC119, SIN3A, and NFKB2,
      interact with most other genes among all the predicted target genes.Hsa-miR
      34a/15a/23a/210/18b/548n/143 is likely to have a role in the pathogenesis of
      SSNHL.

PMID- 29381992
TI  - The prevalence, metabolic risk and effects of lifestyle intervention for
      metabolically healthy obesity: a systematic review and meta-analysis: A PRISMA
      compliant article.
AB  - BACKGROUND: We conducted a systematic review and meta-analysis to firstly obtain
      a reliable estimation of the prevalence of metabolically healthy obese (MHO)
      individuals in obesity, then assessed the risk of developing metabolic
      abnormalities (MA) among MHO individuals. At last, we evaluated the effects of
      traditional lifestyle interventions on metabolic level for MHO subjects. METHODS:
      A systematic review and meta-analysis (PRISMA) guideline were conducted, and
      original studies were searched up to December 31, 2016. The prevalence of MHO in
      obesity from each study was pooled using random effects models. The relative
      risks (RRs) were pooled to determine the risk of developing MA for MHO compared
      with metabolically healthy normal-weight (MHNW) subjects. For the meta-analysis
      of intervention studies, the mean difference and standardized mean differences
      were both estimated for each metabolic parameter within each study, and then
      pooled using a random-effects model. RESULTS: Overall, 40 population-based
      studies reported the prevalence of MHO in obesity, 12 cohort studies and 7
      intervention studies were included in the meta-analysis. About 35.0% obese
      individuals were metabolically healthy in the obese subjects. There were dramatic
      differences in the prevalence among different areas. However, 0.49 (95%
      confidence intervals [CI]: 0.38 to 0.60) of the MHO individuals would develop one
      or more MA within 10 years. Compared with MHNW subjects, the MHO subjects
      presented higher risk of incident MA (pooled RR = 1.80, 95%CI: 1.53-2.11).
      Following intervention, there was certain and significant improvement of
      metabolic state for metabolically abnormal obesity (MAO) subjects. Only diastolic
      blood pressure had reduced for MHO individuals after intervention. CONCLUSIONS:
      Almost one-third of the obese individuals are in metabolic health. However, they
      are still at higher risk of advancing to unhealthy state. Therefore, it is still
      needed to advise MHO individuals to maintain or adopt a healthy lifestyle, so as
      to counterbalance the adverse effects of obesity.

PMID- 29381993
TI  - Effects of nefopam on emergence agitation after general anesthesia for nasal
      surgery: A prospective, randomized, and controlled trial.
AB  - BACKGROUND: Emergence agitation (EA) occurs frequently after nasal surgery. N
      methyl-D-aspartate (NMDA) receptor antagonists and analgesics, such as fentanyl,
      have been shown to prevent EA. Nefopam inhibits the NMDA receptor and shows a
      potent analgesic effect. We investigated the effects of nefopam on EA in patients
      undergoing nasal surgery. METHODS: In this prospective, double-blind study, 100
      adult patients were allocated randomly to 1 of 2 groups (each n = 50). Patients
      received 20 mg of nefopam in 98 mL of saline for 20 minutes immediately after
      induction of anesthesia (nefopam group) or 100 mL of saline (control group) in
      the same manner. After surgery, the incidence and degree of EA, time for
      extubation, hemodynamic parameters, and adverse events were evaluated by an
      observer blinded to the group allocation. RESULTS: The overall incidence of EA
      was lower in the nefopam group than in the control group (34% [17/50] vs 54%
      [27/50], respectively; P = .044). The incidence of severe EA was also lower in
      the nefopam group than in the control group (8% [4/50] vs 38% [19/50],
      respectively; P = .001). Heart rate (HR) was higher in the nefopam group than in
      the control group from the end of surgery to 3 minutes after extubation (P =
      .008). Time for extubation and adverse events were similar between groups.
      CONCLUSIONS: Nefopam infusion is effective in preventing and reducing the
      severity of EA after nasal surgery without a delay in extubation. However,
      caution is required regarding the increase in HR.

PMID- 29381994
TI  - The efficacy of combined therapy with metronidazole and broad-spectrum
      antibiotics on postoperative outcomes for pediatric patients with perforated
      appendicitis.
AB  - The aim of this study was to evaluate the efficacy of combined therapy with
      metronidazole and broad-spectrum antibiotics for patients with perforated
      appendicitis who underwent surgical intervention.Broad-spectrum antibiotic
      therapy is warranted in the treatment of perforated appendicitis. Metronidazole
      has been used as anaerobic antimicrobial therapy. However, few studies about the
      use of metronidazole in perforated appendicitis have been reported.The medical
      records of 249 patients treated with metronidazole combined with broad-spectrum
      antibiotics following perforated appendicitis surgery were reviewed
      retrospectively and compared with the medical records of 149 patients treated
      only with broad-spectrum antibiotics. Propensity score matching was performed to
      adjust for selected baseline variables. Clinical outcomes, including
      postoperative complications and length of hospital stay, were compared between
      the 2 groups.No differences were found between the use of combined therapy with
      metronidazole and the use of solely broad-spectrum antibiotic agents with regard
      to postoperative duration of intravenous antibiotic treatment (6.8 +/- 1.3 vs 7.9
      +/- 2.1 days, respectively, P = .18), inflammation variables at POD 5 (white
      blood cell [WBC] [risk ratio [RR], 1.06; 95% confidence interval [CI], 0.67-1.93,
      P = .15] and C-reactive protein [CRP] [RR, 1.18; 95% CI, 0.73-2.25, P = .36])
      (Table 2), and the mean postoperative length of hospital stay (LOS) (RR, 0.68,
      95% CI, 0.41-0.94, P = .41). There were also no differences in the incidence of
      postoperative complications, including the intra-abdominal or pelvic abscess rate
      (7[7.1%] vs 9[9.2%], respectively, P = .40), the incidence of wound infection
      (14[14.3%] vs 15[15.3%], respectively, P = .50), and the 30-day readmission rate
      (9[9.2%] vs 12[12.2%], respectively, P = .32).Regarding overall postoperative
      outcomes and complications, our study demonstrated no beneficial clinical effects
      of metronidazole administration in patients with perforated appendicitis who
      underwent surgical intervention. Therefore, metronidazole is not indicated when
      broad-spectrum antibiotics such as aminopenicillins with beta-lactam inhibitors
      or carbapenems and select cephalosporins are used.

PMID- 29381995
TI  - CXCL13 and TH1/Th2 cytokines in the serum and cerebrospinal fluid of
      neurosyphilis patients.
AB  - Neurosyphilis is a chronic infectious disease with involvement of central nervous
      system infection by Treponema pallidum. This study was to investigate the
      contents of B lymphocyte chemokine 1 (BLC-1/chemokine [C-X-C motif] ligand 13),
      Th1 cytokines (Interleukin [IL]-2, IL-12, and Interferon [IFN]-gamma), and Th2
      cytokines (IL-6 and IL-10) in serum and cerebrospinal fluid (CSF) of HIV-negative
      patients with neurosyphilis before and after treatment, aiming to elucidate roles
      of CXCL13 and Th1/Th2 cytokines in immune response to and pathogenesis of
      neurosyphilis.Enzyme-linked immunosorbent assay was employed to detect the
      contents of CXCL13, IL-2, IL-12, IFN-gamma, IL-6, and IL-10 in serum and CSF of
      47 HIV-negative patients with neurosyphilis, 36 syphilis patients without
      neurological involvement and 23 controls (noninfectious intracranial disease)
      before, 3 and 12 months after treatment with high dose penicillin.Results showed
      that there was no significant difference in blood CXCL13 content among 3 groups
      (P > .05); CSF CXCL13 content in neurosyphilis patients was significantly higher
      than in other 2 groups (P < .001), and positively related to leucocyte count,
      protein concentration, and IgG index. IL-6 and IL-10 contents of the serum and
      CSF in neurosyphilis patients were markedly higher than in other 2 groups (P <
      .05 or .01), but IL-2, IL-12, and IFN-gamma of the serum and CSF were
      significantly lower than in other 2 groups (P < .05 or .01). The IL-6, IL-10, IL
      2, IL-12, and IFN-gamma contents of the serum and CSF were comparable between
      control group and syphilis group (P > .05). CSF CXCL13 content was positively
      related with IL-6 and IL-10 content, while negatively related to IL-12 content in
      neurosyphilis patients. CSF IL-6 content was negatively related with IL-12
      content. In neurosyphilis patients, the CSF CXCL13 content reduced significantly
      at 3 and 12 months (P < .001), the CSF IL-2 and IL-12 contents increased
      significantly at 12 months, and CSF IL-6 contents reduced significantly at 12
      months after treatment (P < .05 or .01).It is concluded that neurosyphilis
      patients did not have normal immune function. CXCL13 and Th1/Th2 cytokines are
      involved in the immune response of neurosyphilis patients. CSF CXCL13 and Th1/Th2
      cytokines contents may be used for the diagnosis and evaluation of therapeutic
      efficacy of neurosyphilis.

PMID- 29381996
TI  - Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: A case
      report and literature review.
AB  - RATIONALE: Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma
      (TL-LGNPPA) is an extremely rare malignant nasopharyngeal tumor with features
      resembling papillary thyroid carcinoma including nuclear positive expression of
      thyroid transcription factor-1 (TTF-1). PATIENT CONCERNS: A 64-year-old male
      presented with nasal bleeding and a foreign body sensation of the nasopharynx.
      Laryngoscopy revealed a 2.0-cm broad-based mass with a smooth surface on the
      posterior wall of the nasopharynx. A biopsy was obtained. DIAGNOSES:
      Histopathologic examination demonstrated tumor cells arranged in both papillary
      and glandular architecture. The tumor cells express nuclear immunoreactivity for
      TTF-1. The diagnosis of TL-LGNPPA was made. INTERVENTIONS: After the patient was
      diagnosed with TL-LGNPPA, he underwent complete surgical resection. OUTCOMES:
      There was no recurrence or evidence of metastatic disease at the 12-month follow
      up. LESSONS: TL-LGNPPA is easy to misdiagnose as metastatic papillary thyroid
      carcinoma or other relative primary adenocarcinomas. It is important to have a
      broad differential diagnosis and know the key features of each entity because the
      prognosis and clinical treatment of each may differ.

PMID- 29381997
TI  - Vascular Ehlers-Danlos syndrome with cryptorchidism, recurrent pneumothorax, and
      pulmonary capillary hemangiomatosis-like foci: A case report.
AB  - RATIONALE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant
      inherited collagen disorder caused by defects or deficiency of pro-alpha 1 chain
      of type III procollagen encoded by COL3A1. vEDS is characterized not only by soft
      tissue manifestations including hyperextensibility of skin and joint
      hypermobility but also by early mortality due to rupture of arteries or vital
      organs. Although pulmonary complications are not common, vEDS cases complicated
      by pneumothorax, hemothorax, or intrapulmonary hematoma have been reported. When
      a patient initially presents only with pulmonary complications, it is not easy
      for clinicians to suspect vEDS. PATIENT CONCERNS: We report a case of an 18-year
      old high school student, with a past history of cryptorchidism, presenting with
      recurrent pneumothorax. DIAGNOSES: Routine laboratory findings were unremarkable.
      Chest high resolution computed tomographic scan showed age-unmatched
      hyperinflation of both lungs, atypical cystic changes and multifocal ground glass
      opacities scattered in both lower lobes. His slender body shape, hyperflexible
      joints, and hyperextensible skin provided clue to suspicion of a possible
      connective tissue disorder. INTERVENTIONS: The histological examination of the
      lung lesions showed excessive capillary proliferation in the pulmonary
      interstitium and pleura allowing the diagnosis of pulmonary capillary
      hemangiomatosis (PCH)-like foci. Genetic study revealed COL3A1 gene splicing site
      mutation confirming his diagnosis as vEDS. OUTCOMES: Although his diagnosis vEDS
      is notorious for fatal vascular complication, there was no evidence of such
      complication at presentation. Fortunately, he has been followed up for 10 months
      without pulmonary or vascular complications. LESSONS: To the best of our
      knowledge, both cryptorchidism and PCH-like foci have never been reported yet as
      complications of vEDS, suggesting our case might be a new variant of this
      condition. This case emphasizes the importance of comprehensive physical
      examination and history-taking, and the clinical suspicion of a possible
      connective tissue disorder when we encounter cases with atypical presentation
      and/or unique chest radiologic findings especially in young patients.

PMID- 29381998
TI  - Genetic polymorphism analysis of cytochrome P4502E1 (CYP2E1) in a Chinese Tibetan
      population.
AB  - Cytochrome P4502E1 (CYP2E1) gene genetic polymorphisms vary markedly in frequency
      among different ethnic and racial groups.We studied the genotype distributions
      and allele frequencies of 3 CYP2E1 polymorphisms: CYP2E11A, CYP2E17A, and
      CYP2E17C by polymerase chain reaction technique in a sample of 100 healthy
      subjects representing Tibetan population.The frequencies of CYP2E11A, 7A, and 7C
      alleles were 0.705, 0.125, and 0.170, respectively. Compared with other
      populations, we found that the allele frequencies of the variants -352A>G
      (rs2070672) and -333A>T (rs2070673) in this Tibetan population have significant
      differences compared with European-American, African-American, Japanese, Korean,
      and other different geographic areas in Chinese Han population. Furthermore, the
      results of protein prediction revealed that the variant 6397G>A (rs61710826)
      could influence the protein structure and function.These findings in this study
      would be valuable for pharmacogenetics for drug therapy and drug discovery.
      However, further studies in larger samples are warranted to confirm our results.

PMID- 29381999
TI  - Abdominal surgery in patients with essential thrombocythemia: A case report and
      systematic review of literature.
AB  - INTRODUCTION: Essential thrombocythemia/thrombocytosis (ET) is characterized by
      increased bleeding and thrombosis risk during the perioperative period. We report
      the case of a woman with ET and sigmoid colon cancer, in whom the postoperative
      course was complicated by anastomotic bleeding. A systematic review was conducted
      to seek guidance for the management of such patient in the perioperative period.
      METHODS: A systematic literature review was conducted using EMBASE, Medline, and
      PubMed databases to detect relevant English language articles. Published studies
      with full-text articles were included. Two authors independently searched and
      extracted the data. Any differences were resolved by consensus. Studies on
      abdominal surgery were manually retrieved. RESULTS: Four case reports (including
      our case report) that described abdominal surgery in patients with ET were
      included. All patients were females, with a mean age of 47 years. Laparoscopic
      surgery was performed in 2 patients, and open surgery was performed in the other
      2 patients. Two patients had postoperative bleeding that occurred on the first
      postoperative day. There was one case of pseudohyperkalemia after surgery and one
      case of Budd-Chiari syndrome caused by hepatic vein thrombosis. No guidelines for
      patients with ET undergoing abdominal surgery were found. CONCLUSION: In
      conclusion, there are currently no definitive guidelines for the perioperative
      management of patients with ET. Furthermore, there are few reports of ET in
      patients with malignancy undergoing surgery. Further studies in this unique group
      of patients are required.

PMID- 29382000
TI  - Endovascular management of renal artery aneurysms induced by neurofibromatosis
      type 1: A case report.
AB  - RATIONALE: Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder
      characterized by cafe au lait macules and neurofibromatosis. Renal artery
      aneurysms are relatively uncommon. Endovascular techniques are effective in
      treating renal aneurysms but successful cases are rarely reported in NF-1 adults.
      PATIENT CONCERNS: The patient was one 23-year-old female presented with
      hypertension, multiple cafe-au-lait spots >=15 mm, and plexiform neurofibroma.
      Renal artery aneurysms were found by ultrasound. DIAGNOSES: NF-1 was diagnosed
      based on clinical manifestations and confirmed by gene test. Renal artery
      aneurysms were diagnosed based on computed tomography. INTERVENTIONS: Bilateral
      renal artery angiography was performed and 3 aneurysms were found sequentially on
      the left anterior superior segmental artery. Microcoil embolization of aneurysms
      was undertaken. OUTCOMES: The patient's blood pressure decreased after the
      procedure with reduction of medicine. A 3-month follow-up unilateral selective
      renal angiogram demonstrated little change in size of aneurysms, and no
      opacification of the aneurysmal sac was found. Serum creatinine remained in
      normal range at 3-month. LESSONS: Successful endovascular treatment for NF-1
      related renal artery aneurysms in adults is reported for the 1st time with
      preserved renal function and improved hypertension. Endovascular procedure is
      considered to be feasible and effective for renal artery aneurysms induced by NF
      1.

PMID- 29382001
TI  - Multiple primary cancer in the female genital system: Two rare case reports and a
      literature review.
AB  - RATIONALE: Multiple primary cancer (MPC) refers to tumors that occur in one or
      multiple organs within the same patient at the same time or at different periods.
      MPC often occurs in the head and neck, but is rarely reported in the female
      genital system. PATIENT CONCERNS: In the present study, we report 2 rare cases
      that presented with tangible lower abdominal tumors. DIAGNOSES: Laboratory tests,
      pelvic ultrasound (US), computed tomography (CT), and fast histopathological
      examinations during surgery indicated a diagnosis of MPC. INTERVENTIONS: The 2
      patients all received radical resections of multiple tumors. OUTCOMES:
      Postsurgical histopathological and immunohistochemical examinations further
      confirmed primary endometrial cancer and right ovarian cancer in Case 1, and
      primary cervical cancer and left ovarian cancer of Case 2. The 2 patients all
      recovered well without obvious complications. LESSONS: Our study demonstrated
      that female genital MPC should be noted for patients with multiple genital
      tumors. In addition, accurately diagnosis and radical surgical treatment should
      be well performed.

PMID- 29382002
TI  - Latent scurvy with tiredness and leg pain in alcoholics: An underestimated
      disease three case reports.
AB  - RATIONALE: Scurvy is often diagnosed at the state of well-established signs as,
      for example, skin and visceral purpura, gums involvement, loss of healthy teeth,
      which derive mostly from disturbance of collagen metabolism. Little is known
      about the state of latent scurvy, which symptoms are nonspecific and may mimic
      more common conditions such as weakness, leg pain, and muscle aching. PATIENT
      CONCERNS: We report 3 cases of extreme lassitude and leg pain in alcoholics. In 2
      of the 3 cases, discreet classic symptoms such as petechiae or hyperkeratosis of
      the legs involving collagen metabolism were also present. DIAGNOSES: Latent
      scurvy has been diagnosed thanks to historical experimental data reporting and
      undetectable ascorbic acid levels. INTERVENTIONS: In addition to the treatments
      recommended by the French Alcohol Society, patients were given oral vitamin C 500
      mg to 1000 mg per day for at least three months. OUTCOMES: Vitamin C
      supplementation allowed the regression of the symptoms, greatly improved the
      quality of life, and gave the possibility to return to work. Cartinine, requiring
      vitamin C for its hydroxylation, is an essential cofactor in the transport of
      long-chain fatty acid into mitochondrial matrix. Therefore, it plays an important
      role in energy production via beta-oxidation. It is thought that carnitine
      metabolism impairment is responsible for weakness or muscle aching. LESSONS: We
      recommend being aware of the possibility of latent scurvy in chronic alcohol
      abusers. The vitamin C supplementation and dietetic recommendation eating fresh
      fruit and vegetables may help to cure tiredness and to return more easily to
      socialization and to work.

PMID- 29382003
TI  - Hemoglobin Hornchurch [beta43 (CD2) Glu > Lys; HBB: c.130G > A] in a Chinese boy
      complicated with thrombocytopenia: A case report and literature review.
AB  - RATIONALE: Hemoglobin Hornchurch is regarded as an asymptomatic hemoglobinopathy
      with no obvious hematological or clinical abnormalities. Recently, we identified
      hemoglobin Hornchurch in a 13-year-old Chinese boy complicated with
      thrombocytopenia, which displayed instability in isopropanol precipitation test.
      PATIENT CONCERNS: In this case report, we reported a Chinese boy with hemoglobin
      Hornchurch complicated by thrombocytopenia. The patients have been misdiagnosed
      as aplastic anemia and myelodysplastic syndrome before. DIAGNOSES: Hemolysis
      tests, high-performance liquid chromatography, and HBB gene sequencing identified
      the E44K (G>A) mutation. Isopropanol precipitation test showed instability in
      hemoglobin Hornchurch. INTERVENTIONS: The patient was given immunosuppressive
      therapy for 3 months. OUTCOMES: His general conditions have improved along with
      the recovery of the hemogram index. LESSONS: Further research is needed to
      clarify the relation between structural abnormality and functional properties of
      hemoglobin Hornchurch. This second case of hemoglobin Hornchurch indicates that
      there might be more hemoglobin variants or their carriers in the Chinese
      population.

PMID- 29382004
TI  - Acute superior mesenteric vein thrombosis associated with abdominal trauma: A
      rare case report and literature review.
AB  - RATIONALE: Acute mesenteric vein thrombosis (MVT) is defined as new-onset
      thrombosis of the mesenteric vein without evidence of collateralization, finally
      resulting in extensive intestinal infarction. MVT may be idiopathic or be caused
      by conditions responsible for thrombophilia and acquired risk factors. To date,
      there have been few reports of MVT after trauma. Herein we describe our
      experiences treating three patients with MVT. PATIENT CONCERNS: Case 1 was a 44
      year-old man with transverse colon mesenteric hematoma after blunt abdominal
      trauma. Case 2 was a 55-year-old man with jejunal transection after a traffic
      accident. Case 3 was a 26-year-old man presented with multiple abdominal stab
      bowel injury. DIAGNOSES: A 1-week follow-up abdominal computed tomography scan
      showed superior mesenteric vein thrombosis in all of three patients.
      INTERVENTIONS: All patients were treated with anticoagulant for 3 or 6 months.
      OUTCOMES: MVTs were completely resolved without any complications. LESSONS: If
      early diagnosis and treatment could be available, anticoagulation alone might be
      adequate for the treatment of SMVT associated with trauma. Early anticoagulation
      in patients with acute SMVT may avoid the grave prognosis observed in patients
      with arterial thrombosis.

PMID- 29382005
TI  - Successful treatment of pachydermoperiostosis patients with etoricoxib, aescin,
      and arthroscopic synovectomy: Two case reports.
AB  - RATIONALE: Pachydermoperiostosis (PDP) is a rare hereditary disorder that affects
      the skin and bones. PDP is characterized by periostosis, digital clubbing, and
      pachydermia. Previous studies demonstrated that increased prostaglandin E2 (PGE2)
      levels resulting from defective protein degradation pathways play a crucial role
      in PDP pathogenesis, and males were more commonly and severely affected than
      females. Moreover, nearly all PDP patients suffer from refractory arthralgia.
      Although several different treatment modalities are used for PDP, therapy for
      this disease remains challenging. PATIENTS CONCERNS: Two cases of PDP showing
      symptoms consistent with polyarthritis and arthralgia that mainly affected the
      knees and ankles. DIAGNOSES: The diagnostic criteria for PDP include digital
      clubbing, periostosis, and pachydermia. The 2 patients were diagnosed as PDP
      based on the finger clubbing, facial cutis furrowing, knee and ankle arthritis,
      and radiographic evidence of periosteal proliferation. INTERVENTIONS: Patient 1
      had massive joint effusion that was treated by oral administration of etoricoxib
      and aescin combined with arthroscopic synovectomy, whereas Patient 2 had mild
      joint swelling and accepted only oral medication. OUTCOMES: Clinical symptoms of
      the 2 patients greatly improved after the treatment. During the 1-year follow-up,
      the patient experienced no adverse effects or recurrence. LESSONS: The
      therapeutic results showed that oral etoricoxib could reduce inflammation and
      retard progression of pachydermia, or even relieve facial skin furrowing, but had
      limited efficacy for arthralgia. However, oral aescin had satisfactory efficacy
      for arthralgia. Thus, etoricoxib combined with aescin is a safe and effective
      treatment for PDP. Meanwhile, arthroscopic synovectomy can be used to treat joint
      effusion, but had no therapeutic effect on arthralgia. Therefore, postoperative
      oral medications would be needed as subsequent therapy for joint problems. In
      conclusion, this study proposes an effective and safe treatment plan to address
      symptoms experienced by PDP patients.

PMID- 29382006
TI  - Pure acinic cell carcinoma of the breast: A case report and literature review.
AB  - RATIONALE: Acinic cell carcinoma (AcCC) of the breast is a rare histological type
      of malignant epithelial neoplasm exhibiting acinic cell differentiation. PATIENT
      CONCERNS: A 52-year-old woman presented to the hospital with a palpable mass over
      the upper outer quadrant of the right breast. DIAGNOSES: Physical examination
      revealed an irregular mass in the lateral upper quadrant of the left breast,
      approximately 1.5 cm in diameter. Histologically, the tumor cells were round to
      oval, had displaced nuclei with striking single nucleoli and basophilic
      cytoplasm, and contained large coarse cytoplasmic granules. They showed an
      infiltrating growth pattern with a combination of cystic and cribriform feature.
      We diagnosed the tumor as AcCC of the breast. INTERVENTIONS: The patient was
      given a simple mastectomy and sentinel lymph node biopsy. After the surgery, AcCC
      of the breast was confirmed histologically. OUTCOMES: The patient was symptom
      free 3 months after surgery. LESSONS: AcCC of the breast is a very rare tumor,
      and its prognosis appears to be good. Thus, treatment followed the guidelines for
      invasive breast carcinoma and no further therapy was suggested by oncologists
      based on the tumor biology.

PMID- 29382008
TI  - Laparoscopic surgery assisted by colonoscopy for a submucosal cecal fecalith
      presenting as acute appendicitis: A case report.
AB  - RATIONALE: A cecal submucosal fecalith is extremely rare and is likely to be
      misdiagnosed as appendicitis with an incarcerated fecalith. PATIENT CONCERNS:
      This review presents the case of a female patient complaining of recurrent
      abdominal pain in the right lower quadrant, similar to the clinical symptoms of
      appendicitis. Physical examination revealed an abdominal tenderness in the right
      lower quadrant without rebound tenderness or muscular tension. An ultrasound
      examination found a mass located in the right lower abdomen. Computed tomography
      showed a high-density shadow in the cecal cavity. DIAGNOSES: A fecalith was
      detected in the submucosal cecal wall. The postoperative pathologic examination
      showed that the fecalith was located in the submucosa. INTERVENTIONS: A partial
      cecal excision was performed under laparoscopic surgery assisted by colonoscopy.
      OUTCOMES: The patient was discharged 1 week after surgery without postoperative
      complications. LESSONS: Fecaliths should be considered in the differential
      diagnosis of submucosal occupying lesions of the cecum.

PMID- 29382007
TI  - Concurrent injection of dexamethasone intravitreal implant and anti-angiogenic
      agent in patients with macular edema: A retrospective cohort study.
AB  - To evaluate the safety and efficiency in macular edema patients who concurrently
      received a single injection of a dexamethasone intravitreal implant (DEX, 0.7 mg)
      and ranibizumab (2.3 mg).A retrospective cohort study was conducted, and medical
      records from 2012 to 2016 were reviewed. Patients who received concurrent DEX and
      ranibizumab injections with a follow-up period of at least 3 months were enrolled
      in the study group. An age and gender-matched group received ranibizumab
      injections and was designated the control group. The best-corrected visual acuity
      (BCVA), central macular thickness (CMT) and intraocular pressure (IOP) were
      included in the analysis. Steroid-induced ocular hypertension (SIOH) is defined
      as either an elevation of more than 10 mmHg from baseline or a single IOP
      measurement of more than 30 mmHg.A total of 26 patients were enrolled in the
      current study with 13 patients in each group. Both the BCVA (P = .04) and CMT (P
      < .01) achieved significant improvement after the follow-up period in the study
      group. The IOP increased after the injection but no significant elevation was
      observed throughout the follow-up period in the study group (P = .15). For SIOH,
      1 patient in the study group had an elevated IOP of 10 mmHg (7.7%) at 2
      postoperative months, and no single IOP measurement of more than 30 mmHg was
      obtained. Five patients (38.5%) in the study group received medical treatment
      that successfully retarded their IOP elevation, and no individuals required
      surgical management. In the control group, there were no significant fluctuations
      concerning BCVA, CMT, and IOP, and no ocular hypertension was observed. According
      to the inter-group analysis, the CMT and BCVA recovered more significantly in the
      study group than in the control group.Concurrent injection of DEX and ranibizumab
      is a preliminary method that shows effectiveness in treating ME. Furthermore,
      safety is also guaranteed, with moderate levels of severity and transient IOP
      elevation being observed. A future large-scale study is necessary to evaluate the
      long-term effects and safety of this combined treatment.

PMID- 29382009
TI  - Patellar tendon ossification after retrograde intramedullary nailing for distal
      femoral shaft fracture: A case report and review of the literature.
AB  - RATIONALE: Retrograde femoral nailing was one of the most important treatment
      means for distal femoral shaft fracture. However, studies regarding heterotopic
      ossification of the patellar tendon after retrograde intramedullary nailing for
      distal femoral shaft fracture are limited. We herein present a rare complication,
      namely heterotopic ossification of the patellar tendon, after retrograde
      intramedullary nailing for displaced femoral shaft fracture. PATIENT CONCERNS: We
      present a case of 25-year-old male with displaced femoral shaft fracture who was
      treated by retrograde intramedullary nailing. DIAGNOSES: During the period of
      follow-up, the patient developed symptomatic heterotopic ossification of the
      patellar tendon with extensively hard ossification area. INTERVENTIONS: Open
      surgery was recommended, but the patient has refused further treatment. OUTCOMES:
      The patient resulted in pain and restricted the range of motion of the affected
      knee. LESSONS: This case stresses the importance of longer-term follow-up and
      further attention into the possibility of heterotopic ossification of the
      patellar tendon.

PMID- 29382010
TI  - CT and PET/CT findings of primary pulmonary diffuse large B-cell lymphoma: One
      case report and literature review.
AB  - RATIONALE: Primary pulmonary diffuse large B-cell lymphoma (PPL-DLBCL) is rare
      and its clinical manifestations lack specificity. In this report, we present one
      case of PPL-DLBCL with complete clinical and imaging data, including uncontrast
      enhanced CT, contrast-enhanced CT, and positron emission tomography (PET)/CT.
      Previous cases will also be reviewed and summarized. PATIENT CONCERNS: A 62-year
      old woman was hospitalized due to a swelling pain located in the right side of
      her back that persisted for >1 month. Local CT examination indicated a pulmonary
      infection and anti-infective therapy was administered; however, her symptoms did
      not improve. In the hospital, a lung CT scan with enhancement showed
      hyperintensity of the right upper lobe (RUL), ill-defined margins, inhomogeneous
      density, with air bronchograms, and mild-to-moderate enhancement. PET/CT showed a
      slight hyperintensity of mass with high uptake (about 14.7 standardized uptake
      value [SUV]), and no high uptake was found in other locations. INTERVENTIONS: A
      CT-guided percutaneous needle biopsy with Tru-Cut needles was performed.
      DIAGNOSES: The final diagnosis was PPL-DLBCL. OUTCOMES: After 4 rounds of
      chemotherapy using the rituximab-cyclophosphamide hydroxydaunorubicin oncovin
      prednisolone (R-CHOP) regimen, the patient's pain was significantly relieved.
      LESSONS: Finally, the PPL-DLBCL manifestation was similar to other types of PPL
      clinical manifestations and CT manifestations, but the PPL-DLBCL PET/CT showed an
      apparent, high metabolism. CT-guided percutaneous transthoracic needle biopsy can
      clearly diagnose the disease.

PMID- 29382011
TI  - Biodegradable polymer drug-eluting stents versus first-generation durable polymer
      drug-eluting stents: A systematic review and meta-analysis of 12 randomized
      controlled trials.
AB  - BACKGROUND: Even if drug-eluting stents (DES) showed beneficial effects in
      patients with coronary artery diseases (CADs), limitations have been observed
      with the first-generation durable polymer DES (DP-DES). Recently, biodegradable
      polymer DES (BP-DES) have been approved to be used as an alternative to DP-DES,
      with potential benefits. We aimed to systematically compare BP-DES with the first
      generation DP-DES using a large number of randomized patients. METHODS:
      Electronic databases were searched for randomized controlled trials (RCTs)
      comparing BP-DES with first-generation DP-DES. The main endpoints were the long
      term (>=2 years) adverse clinical outcomes that were reported with these 2 types
      of DES. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) and
      the analysis was carried out by RevMan 5.3 software. RESULTS: Twelve trials with
      a total number of 13,480 patients (7730 and 5750 patients were treated by BP-DES
      and first-generation DP-DES, respectively) were included. During a long-term
      follow-up period of >=2 years, mortality, myocardial infarction (MI), target
      lesion revascularization (TLR), and major adverse cardiac events (MACEs) were not
      significantly different between these 2 groups with OR: 0.84, 95% CI: 0.66-1.07;
      P = .16, I = 0%, OR: 1.01, 95% CI: 0.45-2.27; P = .98, I = 0%, OR: 0.91, 95% CI:
      0.75-1.11; P = .37, I = 0% and OR: 0.86, 95% CI: 0.44-1.67; P = .65, I = 0%,
      respectively. Long-term total stent thrombosis (ST), definite ST, and probable ST
      were also not significantly different between BP-DES and the first-generation DP
      DES with OR: 0.77, 95% CI: 0.50-1.18; P = .22, I = 0%, OR: 0.71, 95% CI: 0.43
      1.18; P = .19, I = 0% and OR: 1.31, 95% CI: 0.56-3.08; P = .53, I = 6%,
      respectively. CONCLUSION: Long-term mortality, MI, TLR, MACEs, and ST were not
      significantly different between BP-DES and the first-generation DP-DES. However,
      the follow-up period was restricted to only 3 years in this analysis.

PMID- 29382012
TI  - Coenzyme Q10 supplementation therapy for 2 children with proteinuria renal
      disease and ADCK4 mutation: Case reports and literature review.
AB  - RATIONALE: Mitochondrial nephropathy has a poor prognosis and often progresses to
      the end-stage renal disease. Renal pathology often is focal segmental
      glomerulosclerosis (FSGS) and does not respond to steroid therapy or
      immunosuppressive therapy. Some patients are benefited from the therapy of
      coenzyme Q10, which affect the synthesis pathway of coenzyme Q10. PATIENT
      CONCERNS: Herein, we report 2 cases of children with proteinuria renal disease
      with ADCK4 mutation. DIAGNOSES: Proteinuria renal disease with ADCK4 mutation.
      INTERVENTIONS: Compound heterozygous mutation in ADCK4 gene were detected with
      next-generation sequencing and confirmed by Sanger sequencing. Both of the
      patients were given coenzyme Q10 supplementation therapy. OUTCOMES: The first
      patient showed a decreased proteinuria after coenzyme Q10 supplementation
      therapy, while the other was not improved. LESSONS: Based on the cases we
      reported and from the literature, recognition of ADCK4 mutation through early and
      accurate genetic screening could be helpful in avoiding unnecessary toxicities
      and in preventing complications arising in mitochondrial nephropathy.

PMID- 29382013
TI  - The pathogenesis of iodide mumps: A case report.
AB  - RELATION: Iodide mumps is an uncommon condition, induced by iodide-containing
      contrast, and is characterized by a rapid, painless enlargement of the bilateral
      or unilateral salivary gland. At present, the pathogenesis of iodide mumps is not
      yet clear. It may be related to an idiosyncratic reaction, a toxic accumulation
      of iodine in the gland duct, or renal function damage leading to an iodine
      excretion disorder. This paper reports the clinical manifestations and magnetic
      resonance imaging results of one case of iodide mumps, which occurred after
      digital subtraction angiography. PATIENT CONCERNS: A 66-year-old Chinese man
      presented to our department with a 1-month speech barrier and 1 day of vomiting.
      He had the history of high blood sugar, the history of high blood pressure and
      the history of Vitiligo. He had no history of allergies and had never previously
      received iodide-containing contrast. His renal function and other laboratory
      examinations were normal. During the digital subtraction angiography (DSA), the
      patient received approximately 130 mL of nonionic contrast agent (iodixanol).
      Five hours postsurgery, the patient experienced bilateral parotid enlargement
      with no other discomfort, such as pain, fever, skin redness, itching, hives,
      nausea, vomiting, or respiratory abnormalities. DIAGNOSES: We thought the
      diagnosis was iodide mumps. INTERVENTION: Intravenous dexamethasone (5 mg) was
      administered. OUTCOME: 20 hours post-DSA, after which the bilateral parotid
      shrunk. By 4 days postsurgery, the patient's bilateral parotid had recovered
      completely. LESSONS: We found no obvious abnormal sequence signal in diffusion
      magnetic resonance imaging or the corresponding apparent diffusion coefficient.
      Our findings suggest that vasogenic edema may play an important role in the
      pathogenesis of iodide mumps.

PMID- 29382014
TI  - Calcifying fibrous tumor of stomach: A case report.
AB  - RATIONALE: Calcifying fibrous tumor (CFT) is a rare benign soft tissue
      mesenchymal neoplasm. Although the gastrointestinal (GI) tract is the most common
      predilection site of CFT, the clinicians, even including pathologist, generally
      consider it as GI stromal tumor (GIST) or other submucosal tumors such as
      schwannoma and leiomyoma. PATIENT CONCERNS: A 55-year-old man presented with
      complaints of epigastric discomfort and abdominal distention for more than 1
      year. DIAGNOSES: On the basis of endoscopic and computed tomography examination,
      preliminary diagnosis was GIST. INTERVENTIONS: Endoscopic submucosal dissection
      (ESD) surgery was performed to remove the gastric mass. OUTCOMES: The
      histopathological examination revealed a gastric CFT. LESSONS: We present a case
      of gastric CFT, which was misdiagnosed as GIST based on endoscopic and radiologic
      findings.

PMID- 29382015
TI  - Acute myocardial infarction in a young woman with ulcerative colitis: A case
      report and literature review.
AB  - RATIONALE: Myocardial infarction due to nonatherosclerotic coronary thrombosis in
      young woman with ulcerative colitis is rare. PATIENT CONCERNS: A 23-year-old
      Chinese woman with a 3-year history of ulcerative colitis was admitted to the
      coronary care unit due to prolonged chest pain. DIAGNOSES: Myocardial infarction
      due to nonatherosclerotic coronary thrombosis was diagnosed in this young woman.
      LESSONS: Coronary artery thrombosis in ulcerative colitis is a serious condition
      and can occur in the young population.

PMID- 29382016
TI  - Fatal pulmonary thromboembolism after Achilles tendon open repair: A rare case
      report.
AB  - RATIONALE: The operative procedure for Achilles tendon rupture is relatively
      simple, but venous thromboembolism is serious complication with a high incidence
      after Achilles tendon rupture. However, the guideline for thromboprophylaxis in
      Achilles tendon rupture is unclear. PATIENT CONCERNS: The patient was 32-year-old
      male and underwent Achilles tendon open repair surgery. He was healthy and there
      are no abnormal findings other than Achilles tendon rupture. At 3 weeks after
      operation, the episode of loss of consciousness with convulsive movement
      occurred. The next day, suddenly cardiac arrest occurred. DIAGNOSES: Extensive
      pulmonary thromboembolism in both pulmonary arteries was identified in chest
      computed tomography and thrombus was also identified at the left popliteal vein
      on ultrasonography. INTERVENTION: Anticoagulant therapy with heparin sodium was
      performed to manage the pulmonary thromboembolism. OUTCOMES: Brain swelling after
      ischemic brain damage, acute kidney injury, and pneumonia gradually occurred and
      aggravated. His condition became worse and he died about 2 weeks after the
      cardiac arrest episode. LESSONS: Although the incidence of venous thromboembolism
      in Achilles tendon rupture is higher than that in lower leg injury patients,
      guideline for thromboprophylaxis is unclear. We suggest that thromboprophylaxis
      for Achilles tendon rupture should be considered and appropriate guidelines
      should be established.

PMID- 29382017
TI  - Accuracy of pleth variability index compared with inferior vena cava diameter to
      predict fluid responsiveness in mechanically ventilated patients.
AB  - In the intensive care unit (ICU), stable hemodynamics are very important.
      Hemodynamic intervention is often effective against multiple organ failure, such
      as in tissue hypoxia and shock. The administration of intravenous fluids is the
      first step in regulating tissue perfusion.The main objective of this study is to
      compare the performance between 2 methods namely pleth variability index (PVI)
      and IVC distensibily index (dIVC).In this study, the hemodynamic measurements
      were performed before and after passive leg raising (PLR). Measurements were
      obtained, including, PVI, dIVC, and cardiac index (CI). Both CI and dIVC
      measurements were evaluated by transesophageal probe and convex probe
      respectively. The dIVC measurements were taken using M-mode, 2 cm from junction
      between the right atrium and the inferior vena cava. The PVI was measured by
      Masimo Radical-7 monitor, Masimo.A total of 72 patients were included. The dIVC
      at a threshold value of >23.8% provided 80% sensitivity and 87.5% specificity to
      predict fluid responsiveness and was statistically significant (P < .001), with
      an AUC 0.928 (0.842-0.975). The PVI at a threshold value of >14% provided 95%
      sensitivity and 81.2% specificity to predict fluid responsiveness and was
      statistically significant (P < .001), with an AUC 0.939 (0.857-0.982).Both PVI
      and dIVC can be used as a noninvasive method that can be easily applied at the
      bedside in determining fluid responsiveness in all patients with mechanical
      ventilation in intensive care.

PMID- 29382018
TI  - Epidemiological association of olfactory dysfunction with hearing loss and
      dysphonia in the Korean population: A cross-sectional study.
AB  - The aim of the study is to investigate the association between olfactory
      dysfunction (OD), hearing loss, and dysphonia.The cross-sectional data for 17,984
      adults who completed the Korea National Health and Nutrition Examination Surveys
      (2010-12) were analyzed. OD, hearing loss, and dysphonia were assessed using self
      reporting questionnaires. The association of OD with hearing loss and dysphonia
      was evaluated.Hearing loss and dysphonia were significantly more prevalent in
      patients with OD than in those without OD (hearing loss, 28.1% vs 11.3%;
      dysphonia, 11.1% vs 5.9%; both P < .0001). After adjusting for confounders,
      including mental stress and metabolic syndrome, the risk of OD was significantly
      associated with hearing loss and dysphonia, and was greater in those with
      combined hearing loss and dysphonia than in both patients without these
      dysfunctions and in those with a single dysfunction (odds ratio 3.115, 95%
      confidence interval 1.973-4.917).OD was significantly associated with hearing
      loss and dysphonia.

PMID- 29382019
TI  - Infant Central Nervous System Aspergillosis with First-episode of Intracranial
      Hemorrhage: A case report.
AB  - RATIONALE: Central nervous system (CNS) aspergillosis has the characteristics of
      multifocality, polymorphism, and coexistence of pathological types, and missed
      diagnosis and misdiagnosis frequently occur at the initial stage. The thesis
      reports a rare case of infant infection of CNS aspergillosis with the first
      episode of intracranial hemorrhage. PATIENT CONCERNS: An 11-month-old female
      infant suffered convulsion and coma two days after the onset of fever and emesis.
      Its cranial computed tomography (CT) displayed subdural hemorrhage in the left
      tentorium cerebelli and tests indicated normal cerebrospinal fluid (CSF). Three
      days after being hospitalized, the infant had difficulty breathing and its CT
      presents consolidation in the right lung. However, treatment with ceftriaxone
      (ivgtt) had no effect on the baby. DIAGNOSIS: The patient's bronchoalveolar
      lavage fluid (BALF) was cultured into Aspergillus spp, its galactomannan (GM)
      antigen in CSF counted 3.0, higher than that in BALF which counted 2.6, and
      cranial magnetic resonance imaging (MRI) revealed multiple ring reinforced
      tubercles in sulci. Hence it was clinically diagnosed with CNS aspergillosis.
      INTERVENTIONS: Voriconazole for intravenous injection. After the intravenous
      injection, its trough concentration was 4.2 MUg/mL, and it was within the
      recommended range. OUTCOMES: After one week's treatment with voriconazole, the
      infant's consciousness was improved. Four weeks later, with normothermia and
      clear consciousness, the patient was discharged. With oral administration of
      voriconazole up to 16 weeks, its physical state suggests no relapse and cranial
      MRI indicated disappearance of nodules in sulci. LESSONS: CNS aspergillosis with
      first-episode of intracranial hemorrhage probably leads to misdiagnosis and GM
      test combined with cranial MRI can augment its accuracy in the early diagnosis.

PMID- 29382020
TI  - Failed percutaneous kyphoplasty in treatment of stage 3 Kummell disease: A case
      report and literature review.
AB  - RATIONALE: Albeit it is rare, the authors report a stage 3 Kummell disease case.
      It is diagnosed by dynamic thoracic magnetic resonance imaging (MRI). Because
      there is no established strategy on stage 3 Kummell disease, we performed
      percutaneous kyphoplasty at first, but unfortunately made a revision surgery to
      remove the polymethylmethacrylate (PMMA) cement after the failure of percutaneous
      kyphoplasty. PATIENT CONCERNS: A 73-year-old lady with severe back pain due to
      osteoporosis vertebral fracture was admitted to our hospital on June 23, 2016.
      She underwent percutaneous kyphoplasty with the back pain improved shortly.
      Unfortunately, she went back to our hospital due to aggravated back pain and
      partial paralysis on July 25, 2016. DIAGNOSES: Kummell disease, lumbar stenosis,
      lacunar infarction. OUTCOMES: Specially, the compression of spinal cord was
      obvious in the hyperflexion position on dynamic MRI. Even though there was no
      improvement in muscle strength, the patient was satisfied with the back pain
      relief after percutaneous kyphoplasty. But, the same back pain reappeared after
      about 1 month. Then, we took out the PMMA cement and performed posterior
      vertebral column resection. At last, the back pain was relieved again but the
      muscle strength was improved not obviously after operation. At the same time, the
      kyphosis was corrected and the intravertebral stability was achieved. LESSONS:
      Dynamic MRI is helpful in Kummell disease with neurologic symptoms, even if there
      is no obvious compression in the neutral position. Furthermore, the
      intravertebral instability is probably the main reason of the neurologic symptoms
      in this case. Percutaneous kyphoplasty could not reconstruct the intravertebral
      stability. Stage 3 Kummell disease with obvious intravertebral instability should
      be treated by open surgery.

PMID- 29382021
TI  - Altered effective connectivity of resting state networks by acupuncture
      stimulation in stroke patients with left hemiplegia: A multivariate granger
      analysis.
AB  - The aim of this study was to explore the response feature of resting-state
      networks (RSNs) of stroke patients with left hemiplegia by acupuncture
      stimulation.Nineteen stroke patients with left hemiplegia and 17 controls were
      recruited in this study. Resting-state functional magnetic resonance imaging data
      before and after acupuncture were acquired using magnetic scanning. The
      independent component analysis (ICA) was employed to extract RSNs related to
      motion, sensation, cognition, and execution, including sensorimotor network
      (SMN), left and right frontoparietal network (LFPN and RFPN), anterior and
      posterior default mode network (aDMN, pDMN), visual network (VN), and salience
      network (SN). Granger causality method was used to explore how acupuncture
      stimulation affects the causality between intrinsic RSNs in stroke patients.
      Compared with healthy subjects, stroke patients presented the more complex
      effective connectivity. Before acupuncture stimulation, LFPN inputted most
      information from other networks while DMN outputted most information to other
      networks; however, the above results were reversal by acupuncture. In addition,
      we found aDMN reside in between SMN and LFPN after acupuncture.The finding
      suggested that acupuncture probably integrated the effective connectivity
      internetwork by modulating multiple networks and transferring information between
      LFPN and SMN by DMN as the relay station.

PMID- 29382022
TI  - Optimum end-tidal concentration of sevoflurane to facilitate supraglottic airway
      device insertion with propofol at induction allowing spontaneous respiration in
      obese patients: A prospective observational study.
AB  - Obese patients are more likely to encounter with difficult airway management, and
      supraglottic airway device has been adopted to facilitate tracheal intubation.
      The optimum anesthetic concentration for obese patients to insert a supraglottic
      airway device with spontaneous respiration has not been investigated. This study
      was designed to determine the end-tidal concentration of sevoflurane that would
      provide acceptable condition for supraglottic airway device insertion with
      propofol at induction in obese patients without using neuromuscular
      blockade.Thirty elective obese patients [body mass index (BMI) 30-50 kg/m]
      scheduled for bariatric surgery were enrolled in this study. Sevoflurane was
      inhaled at a concentration of 5% after infusion of 1 mg/kg propofol (within 1
      minute) according to lean body weight. The target concentration of sevoflurane
      was initiated at 2.5% with 0.5% as a step size using a modified Dixon up-and-down
      method. Five minutes after target concentration achieved, the insertion of
      supraglottic airway device was attempted.The minimum alveolar concentration of
      sevoflurane for successful insertion of supraglottic airway device calculated
      using up-and-down method were 2.25 (0.53) % for obese patients. The values of the
      effective concentration of sevoflurane for successful supraglottic airway device
      insertion in 50% (EC50) and 95% (EC95) of the obese patients obtained by probit
      regression analysis were 2.09% (95% confidence interval 1.48-2.68) and 3.31% (95%
      confidence interval 2.70-8.12), respectively.We conclude that sevoflurane at a
      minimum alveolar concentration of 2.25% can provide optimal conditions for
      insertion of supraglottic airway device with spontaneous respiration in obese
      patients with 1 mg/kg propofol at induction.

PMID- 29382023
TI  - Case report: remarkable remission of SAPHO syndrome in response to Tripterygium
      wilfordii hook f treatment.
AB  - RATIONALE: SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis)
      syndrome is an autoinflammatory disease with no standardized treatment.
      Tripterygium wilfordii hook f (TwHF) is a Chinese herb with immunosuppressive
      effects and has been used to treat some chronic inflammatory diseases. However,
      it has not been reported as a therapeutic option in SAPHO syndrome. Here we
      present the first report in which a remarkable remission of SAPHO syndrome was
      achieved in response to TwHF. PATIENT CONCERNS: A 57-year-old female patient
      noted swelling and pain at the anterior chest wall and scattered rashes like
      psoriasis vulgaris. Bone scintigraphy demonstrated the classic "bull's head" sign
      and magnetic resonance images indicated bone marrow edema on T5. DIAGNOSES: The
      diagnosis was made by dermatological and osteoarticular manifestations and
      classical "bull's head" sign in bone scintigraphy. INTERVENTIONS: TwHF with a
      priming dose of 20 mg 3 times per day and a gradual dose reduction of 20 mg per
      day in every 3 months. Four months later, methotrexate was added with 10 mg per
      week. OUTCOMES: Osteoarticular symptoms and radiological abnormalities were
      improved dramatically. LESSONS: This case illustrates a promising strategy to
      treat SAPHO syndrome.

PMID- 29382024
TI  - Fimasartan-induced liver injury in a patient with no adverse reactions on other
      types of angiotensin II receptor blockers: A case report.
AB  - RATIONALE: Angiotensin II receptor blockers (ARBs) are widely used for patients
      with hypertension, and fimasartan is a recently approved ARBs. Fimasartan can
      cause headache, dizziness, itching, and coughing. There have been several reports
      of hepatotoxicity in ARBs. However, there have not yet been published reports of
      the hepatotoxicity of fimasartan. PATIENT CONCERNS: A 73-year-old man with
      hypertension experienced liver injury after fimasartan administration. He had a
      previous history of taking 3 types of ARBs each for more than 2 years before
      taking fimasartan, and there were no side effects on ARBs except for fimasartan.
      DIAGNOSES: Other factors that could cause liver injury were excluded in
      diagnostic tests, and fimasartan was suspected to be the causative agent.
      INTERVENTION: Fimasartan was immediately discontinued and the patient was managed
      with supportive care via hepatotonics. DIAGNOSES: Other factors that could cause
      liver injury were excluded in diagnostic tests, and fimasartan was suspected to
      be the causative agent. OUTCOME: The liver injury due to fimasartan was confirmed
      by histology and accidental redosing. LESSONS: We emphasize that liver function
      should be monitored during fimasartan administration because fimasartan may cause
      hepatotoxicity in patients who have no side effects with other types of ARBs. And
      fimasartan-induced liver injury may appear later than other ARBs.

PMID- 29382026
TI  - A case report of tongue metastasis from lung squamous cell carcinoma and
      literature review: Erratum.

PMID- 29382027
TI  - Candida vertebral osteomyelitis (CVO) 28 cases from a 10-year retrospective study
      in France: Erratum.

PMID- 29382025
TI  - Wendan decoction for primary insomnia: Protocol for a systematic review and meta
      analysis.
AB  - BACKGROUND: Insomnia is a widespread complaint in the general population. Wendan
      decoction has been widely applied in the treatment of primary insomnia. However,
      to our knowledge, there has been no systematic review or meta-analysis of
      randomized controlled trails regarding the effectiveness of this treatment. Here,
      we provide a protocol to evaluate the efficacy and safety of Wendan decoction for
      primary insomnia. METHODS AND ANALYSIS: Relevant randomized controlled trials in
      5 English databases [EMBASE, the Cochrane Central Register of Controlled Trials
      (Cochrane Library), PubMed, the Allied and Complementary Medicine Databases
      (AMED), and the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL)], 4 Chinese databases [Chinese Biomedical Literature Database (CBM),
      Chinese Medical Current Content (CMCC), China National Knowledge Infrastructure
      (CNKI), and Wanfang Database] will be comprehensively searched by 2 researchers
      in October 2017. The therapeutic effects according to the Pittsburgh Sleep
      Quality Index (PSQI) will be accepted as the primary outcomes. We will use RevMan
      V.5.3 software as well to compute the data synthesis carefully when a
      metaanalysis is allowed. RESULTS: This study will provide a high-quality
      synthesis of current evidence of Wendan decoction for primary insomnia from
      several aspects including PSQI, the total scores of the Insomnia Severity Index
      (ISI), syndrome according to standards for assessing Traditional Chinese medicine
      and adverse events. CONCLUSION: The conclusion of our systematic review will
      provide evidence to judge whether Wendan decoction is an effective intervention
      for patient with primary insomnia. ETHICS AND DISSEMINATION: The outcomes of this
      systematic review will offer implications of the use of Wendan decoction
      treatment for primary insomnia patients. This knowledge informing recommendations
      will be provided by researchers who are interested in the treatment of primary
      insomnia. The results of this study will be disseminated through presentation at
      a conference and publication of the data in a peer-reviewed journal. PROSPERO
      REGISTRATION NUMBER: PROSPERO CRD 42017065664.

PMID- 29382028
TI  - Intraoperative conversion of artificial cervical disc replacement to anterior
      cervical discectomy and fusion for iatrogenic fracture: A rare case report.
AB  - RATIONALE: Artificial cervical disc replacement (ACDR) has been reported to be an
      effective and safe surgical treatment for cervical spondylosis. However,
      iatrogenic fracture during ACDR surgery has rarely been reported. Considering its
      infrequency, we report a rare clinical case, with the aim of sharing our
      experience and exploring when to convert ACDR to fusion intraoperatively.
      PATIENTS CONCERNS: A 47-year-old woman felt neck pain with weakness and numbness
      in both upper limbs for 5 months. DIAGNOSES: The patient had received discectomy
      and fusion procedure on C3/4 and C5/6 to relieve her radicular pain nearly 4
      years prior. Neurologic examination revealed a diminished sensation at the C6-C8
      skin areas and level Grade-4 power in the left wrist extensor and grip muscle
      strength. Magnetic resonance imaging (MRI) showed disc herniation compressing the
      spinal cord at C6/7. Computed tomography (CT) scans showed intervertebral fusion
      in both the C3/4 and C5/6 segments. INTERVENTIONS: Surgery was performed to
      remove the plate and replace C6/7 with an artificial disc, but a transverse
      cleavage endplate cortical fracture was detected after cutting the blades. Thus,
      we terminated artificial cervical disc replacement intraoperatively and changed
      to discectomy and fusion in C6/7. OUTCOMES: The patient's symptoms were
      remarkably relieved. Postoperative CT scans showed a transverse cleavage fracture
      in the backside of the C6 caudal endplate. Good fusion was achieved after 6
      months. LESSONS: Iatrogenic fracture during ACDR is rare but does occur in clinic
      practice. Complete examination and an alternative approach determined before
      surgery are important for operative safety. Anterior cervical discectomy and
      fusion (ACDF) is recommended as a feasible remedial surgical strategy if ACDR
      fails intraoperatively.

PMID- 29382029
TI  - Acute stent thrombosis after stent-assisted coiling in an intracranial aneurysm
      patient carrying two reduced-function CYP2C19 alleles: A case report.
AB  - RATIONALE: Stent thrombosis (ST) remains a thorny issue in spite of dual
      antiplatelet treatment with aspirin plus clopidogrel after stent-assisted coiling
      (SAC). We report a first case of acute ST after SAC in an intracranial aneurysm
      (IA) patient who carries two reduced-function CYP2C19 alleles. PATIENT CONCERNS:
      A 43-year-old Chinese male carrying two reduced-function CYP2C19 alleles was
      treated with a loading dose of clopidogrel 300 mg and aspirin 300 mg before SAC.
      Unfortunately, life-threatening ST appeared 0.5 h later after SAC. INTERVENTIONS:
      A total of 100000U of urokinase was used to dissolve ST. Meanwhile, tirofiban and
      nodroparin was also administrated to prevent recurrent thrombotic events.
      OUTCOMES: A repeated angiography demonstrated a successful reperfusion after
      thrombolytic treatment. LESSONS: The present case demonstrates that CYP2C19
      allele carriers may lead to a suppressed antiplatelet effect of clopidogrel and a
      high risk of ST in the meantime. Therefore, CYP2C19 genetic testing seems to be
      able to identify patients-at-risk and optimal antiplatelet treatment should be
      considered in these fragile populations.

PMID- 29382030
TI  - A recurrence-free survivor with chemotherapy-refractory small cell lung cancer
      after pneumonectomy: A case report and review of the literature.
AB  - RATIONALE: The optimal therapeutic regimen for chemotherapy-refractory and node
      positive small-cell lung cancer (SCLC) is criticizable for the lack of evidence.
      PATIENT CONCERNS: A patient with locally advanced SCLC was insensitive to the
      first-line chemotherapy of etoposide, irinotecan, and cisplatin. DIAGNOSES: The
      patient was diagnosed as SCLC with mediastinal lymph node metastasis by
      pathological staining. INTERVENTIONS: Salvage pneumonectomy and systematic lymph
      node dissection combined with oral apatinib and mediastinal radiotherapy were
      performed for him. OUTCOMES: The patient survived for more than 2 years without
      recurrence after the operation and adjuvant therapy. LESSONS: For patients with
      chemotherapy-resistant but resectable SCLC, a timely resection combined with
      postoperative radiotherapy and apatinib might be effective.

PMID- 29382031
TI  - Anterior scleritis following intravitreal injections in a patient with rheumatoid
      arthritis: A case report.
AB  - RATIONALE: Surgically induced scleritis is a rare complication following
      ophthalmologic surgery such as cataract surgery, pterygium excision, strabismus
      surgery, and retinal detachment repair. Rheumatoid arthritis (RA) is the
      connective tissue disease most commonly associated with scleritis. PATIENT
      CONCERNS: A 70-year-old woman visited our clinic with complaint of visual
      disturbance, ocular pain, and conjunctival injection in her right eye of 1
      month's duration. She had a stable state of rheumatoid factor positive RA and had
      a history of multiple intravitreal injections placed in the symptomatic right eye
      due to age-related macular degeneration. DIAGNOSES: Anterior scleritis induced by
      multiple intravitreal injections. INTERVENTIONS: Topical and systemic steroids
      were administered. OUTCOMES: Her symptoms and signs were relieved and no
      significant recurrence has been occurred with the maintenance of low dose oral
      steroid. LESSONS: Surgically induced scleritis can also be induced by not only
      major surgical trauma but also by relatively minor trauma such as intravitreal
      injection (especially in patients who have connective tissue disease such as RA).

PMID- 29382032
TI  - A rare case of cavitary lung cancer complicated with mycotic pneumonia and
      bullous emphysema: A case report and review of the literature.
AB  - RATIONALE: The accurate diagnosis and staging of cavitary lung cancer is
      challenging but essential for the choice of therapy; therefore, the differential
      diagnosis of cystic pulmonary lesions needs to be elucidated. PATIENT CONCERNS: A
      patient was admitted with multifocal thin-walled cystic lesions in chest computed
      tomography. DIAGNOSES: The patient had been diagnosed as heterogeneous bullous
      emphysema pathologically about 3 years ago. His diagnosis turned out to be
      metastatic cavitary lung cancer complicated with fungal pneumonia this time.
      INTERVENTIONS: The patient underwent lung volume reduction surgery during his
      first hospitalization. Concurrent systemic chemotherapy and whole brain
      radiotherapy were administered after the diagnosis of cystic lung cancer.
      OUTCOMES: The patient was lost to follow-up after the chemoradiotherapy. LESSONS:
      Cavitary lung cancer should always be kept in mind during differential diagnosis
      of pulmonary cystic lesions. Pathological diagnosis by biopsy and surgery could
      be considered to avoid delayed treatment of malignancy.

PMID- 29382033
TI  - Efficacy and safety of chemoradiation therapy compared with chemotherapy for
      esophageal carcinoma: An updated meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The role of the chemoradiation therapy (CRT) and chemotherapy (CT) in
      the treatment of esophageal carcinoma (EC) remains controversial. Therefore, we
      conducted this meta-analysis to compare the efficacy and safety of CRT with CT in
      the treatment of EC patients. METHODS: PubMed, Embase, Web of Science, and The
      Cochrane library were systematically reviewed for randomized controlled trials
      (RCTs) that compared CRT with CT. Outcomes included overall survival (OS),
      progression-free survival (PFS), pathological complete response (pCR), R0
      resection, recurrence rate, mortality rate, and adverse events. Pooled estimates
      were expressed with hazard ratio (HR) with 95% confidence intervals (95% CIs) and
      risk ratio (RR) with 95% CIs. RESULTS: Eight RCTs involving 1274 patients were
      included in this meta-analysis. Compared with CT, CRT was not associated with
      significantly improved OS (HR = 0.91, 95% CI: 0.82, 1.01; P = .072) and PFS (RR =
      3.62, 95% CI: 1.10, 11.95; P = .035). The pCR rate and R0 resection rate were
      significant higher in the CRT group than that in the CT group (RR = 3.62, 95% CI:
      1.10, 11.95, P = .035; RR = 1.18, 95% CI: 1.09, 1.27, P < .001; respectively). EC
      patients who received CRT had a higher mortality rate (RR = 2.50, 95% CI: 1.14,
      5.48; P = .022) than those treated with CT, and the incidence of grade 3 or 4
      adverse events was similar between the 2 groups (RR = 0.91, 95% CI: 0.62, 1.32; P
      = .612). CONCLUSION: On the basis of the current evidence, our results suggested
      that CRT seemed to have benefit in the radical resection, but no effect in the
      survival benefits. Further large-scale, well-conducted RCTs are needed to verify
      our findings.

PMID- 29382034
TI  - Characterisation of Polyphenol-Containing Extracts from Stachys mucronata and
      Evaluation of Their Antiradical Activity.
AB  - Background: The aromatic plant Stachys mucronata (Lamiaceae) is endemic to the
      island of Crete (southern Greece), but as opposed to other native Greek members
      of this family, this species has never been investigated in the past with regard
      to its polyphenolic composition and antioxidant potency. Methods: Aerial parts of
      S. mucronata were exhaustively extracted and partly fractionated through
      partition, using n-butanol and dichloromethane. Results: Following an initial
      examination, which consisted of estimating the total polyphenol content and the
      antiradical activity, the n-butanol extract was found to be by far the richest in
      polyphenols, exhibiting much stronger antiradical activity compared with the
      dichloromethane counterpart. On this basis, the n-butanol extract was analysed by
      liquid chromatography-diode array-mass spectrometry, to tentatively characterise
      the principal polyphenolic components, which were shown to be flavonol but mainly
      flavone derivatives. Conclusions: The most potent radical-scavenging compounds
      were detected in the n-butanol fraction of the extracts, suggesting that the most
      active antioxidants in S. mucronate are relatively polar. The analyses suggested
      the major constituents to be derivatives of the flavone luteolin, accompanied by
      apigenin analogues, as well as flavonol glycosides and chlorogenate conjugates.

PMID- 29382036
TI  - Botulinum Toxin A for Sialorrhoea Associated with Neurological Disorders:
      Evaluation of the Relationship between Effect of Treatment and the Number of
      Glands Treated.
AB  - Background: Sialorrhoea and drooling are disabling manifestations of different
      neurological disorders. The aim of this study was to evaluate the effects of
      botulinum neurotoxin type A (BoNT/A) injection on hypersalivation in 90 patients
      with neurological diseases of different aetiologies, and to define the minimum
      number of injected salivary glands to reduce sialorrhoea. Determining the minimum
      number of glands that need to be engaged in order to have a significant reduction
      in drooling may be very useful for establishing the minimum total dosage of
      BoNT/A that may be considered effective in the treatment of hypersalivation.
      Methods: Twenty-five mouse units (MU) of BoNT/A (onabotulinumtoxin A, Botox;
      Allergan, Irvine, CA, USA; 100 MU/2 mL, 0.9% saline; or incobotulinumtoxin A,
      Xeomin; Merz Pharma, Germany; 100 MU/2 mL, 0.9% saline) were percutaneously
      injected into the parotid (p) glands and/or submandibular (s) glands under
      ultrasound control. On this basis, patients were divided into three groups. In
      group A (30 patients), BoNT/A injections were performed into four glands; in
      group B (30 patients), into three glands, and in group C (30 patients), into two
      glands. Patients treated in three glands (group B) were divided into two
      subgroups based on the treated glands (2 p + 1 s = 15 patients; 2 s + 1 p = 15
      patients). Similarly, patients being injected in two glands (group C) were
      subdivided into three groups (2 p = 10 patients; 1 p + 1 s = 10 patients; 2 s =
      10 patients). In patients who were injected in three and two salivary glands,
      saline solution was injected into the remaining one and two glands, respectively.
      Assessments were performed at baseline and at 2 weeks after the injections.
      Results: BoNT/A significantly reduced sialorrhoea in 82 out of 90 patients. The
      effect was more evident in patients who had four glands injected than when three
      or two glands were injected. The injections into three glands were more effective
      than injections into two glands. Conclusions: Our results have shown that BoNT/A
      injections induced a significant reduction in sialorrhoea in most patients (91%).
      In addition, we demonstrated that sialorrhoea associated with different
      neurological diseases was better controlled when the number of treated glands was
      higher.

PMID- 29382035
TI  - Corylin Suppresses Hepatocellular Carcinoma Progression via the Inhibition of
      Epithelial-Mesenchymal Transition, Mediated by Long Noncoding RNA GAS5.
AB  - Corylin is a flavonoid extracted from the nuts of Psoralea corylifolia L.
      (Fabaceae), which is a widely used anti-inflammatory and anticancer herb in
      China. Recent studies revealed antioxidant, anti-inflammatory, and bone
      differentiation-promoting effects of corylin. However, there are no studies
      examining the anticancer activity of corylin. In this study, we used cells and
      animal models to examine the antitumor effects of corylin on hepatocellular
      carcinoma (HCC) and then studied its downstream regulatory mechanisms. The
      results showed that corylin significantly inhibited the proliferation, migration,
      and invasiveness of HCC cells and suppressed epithelial-mesenchymal transition.
      We found that the anti-HCC mechanism of corylin's action lies in the upregulation
      of tumor suppressor long noncoding RNA growth arrest-specific transcript 5 (GAS5)
      and the activation of its downstream anticancer pathways. In animal experiments,
      we also found that corylin can significantly inhibit tumor growth without
      significant physiological toxicity. The above results suggest that corylin has
      anti-HCC effects and good potential as a clinical treatment.

PMID- 29382037
TI  - Resuspendable Powders of Lyophilized Chalcogen Particles with Activity against
      Microorganisms.
AB  - Many organic sulfur, selenium and tellurium compounds show considerable activity
      against microorganisms, including bacteria and fungi. This pronounced activity is
      often due to the specific, oxidizing redox behavior of the chalcogen-chalcogen
      bond present in such molecules. Interestingly, similar chalcogen-chalcogen motifs
      are also found in the elemental forms of these elements, and while those
      materials are insoluble in aqueous media, it has recently been possible to unlock
      their biological activities using naturally produced or homogenized suspensions
      of respective chalcogen nanoparticles. Those suspensions can be employed readily
      and often effectively against common pathogenic microorganisms, still their
      practical uses are limited as such suspensions are difficult to transport, store
      and apply. Using mannitol as stabilizer, it is now possible to lyophilize such
      suspensions to produce solid forms of the nanoparticles, which upon resuspension
      in water essentially retain their initial size and exhibit considerable
      biological activity. The sequence of Nanosizing, Lyophilization and Resuspension
      (NaLyRe) eventually provides access to a range of lyophilized materials which may
      be considered as easy-to-handle, ready-to-use and at the same time as
      bioavailable, active forms of otherwise insoluble or sparingly substances. In the
      case of elemental sulfur, selenium and tellurium, this approach promises wider
      practical applications, for instance in the medical or agricultural arena.

PMID- 29382038
TI  - Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye:
      Failures, Successes, and Future Possibilities.
AB  - Vascular endothelial growth factor (VEGF) plays a pivotal role in the development
      of neovascularization and edema from several common chorioretinal vascular
      conditions. The intravitreally injected drugs (aflibercept, bevacizumab,
      conbercept, pegaptanib, and ranibizumab) used to treat these conditions improve
      the visual acuity and macular morphology in most patients. Monthly or bimonthly
      injections were administered in the phase III pivotal trials but physicians
      usually individualize therapy with pro re nata (PRN) or treat and extend
      regimens. Despite these lower frequency treatment regimens, frequent injections
      and clinic visits are still needed to produce satisfactory outcomes. Newly
      developed drugs and refillable reservoirs with favorable pharmacokinetic profiles
      may extend durations of action and require fewer office visits. However, we have
      learned from previous experiences that the longer durations of action seen in
      strategically designed phase III trials often do not translate to less frequent
      injections in real-life clinical practice. Unfortunately, long-acting therapies
      that produce soluble VEGF receptors (encapsulated cell technology and adenovirus
      injected DNA) have failed in phase II trials. The development of longer duration
      therapies remains a difficult and frustrating process, and frequent drug
      injections are likely to remain the standard-of-care for years to come.

PMID- 29382039
TI  - A Low-Cost Data Acquisition System for Automobile Dynamics Applications.
AB  - This project addresses the need for the implementation of low-cost acquisition
      technology in the field of vehicle engineering: the design, development,
      manufacture, and verification of a low-cost Arduino-based data acquisition
      platform to be used in <80 Hz data acquisition in vehicle dynamics, using low
      cost accelerometers. In addition to this, a comparative study is carried out of
      professional vibration acquisition technologies and low-cost systems, obtaining
      optimum results for low- and medium-frequency operations with an error of 2.19%
      on road tests. It is therefore concluded that these technologies are applicable
      to the automobile industry, thereby allowing the project costs to be reduced and
      thus facilitating access to this kind of research that requires limited
      resources.

PMID- 29382040
TI  - Sesquiterpene Lactones from Vernonia cinerascens Sch. Bip. and Their in Vitro
      Antitrypanosomal Activity.
AB  - In the endeavor to obtain new antitrypanosomal agents, particularly sesquiterpene
      lactones, from Kenyan plants of the family Asteraceae, Vernonia cinerascens Sch.
      Bip. was investigated. Bioactivity-guided fractionation and isolation in
      conjunction with LC/MS-based dereplication has led to the identification of
      vernodalol (1) and isolation of vernodalin (2), 11beta,13-dihydrovernodalin (3),
      11beta,13-dihydrovernolide (4), vernolide (5), 11beta,13-dihydrohydroxyvernolide
      (6), hydroxyvernolide (7), and a new germacrolide type sesquiterpene lactone
      vernocinerascolide (8) from the dichloromethane extract of V. cinerascens leaves.
      Compounds 3-8 were characterized by extensive analysis of their 1D and 2D NMR
      spectroscopic and HR/MS spectrometric data. All the compounds were evaluated for
      their in vitro biological activity against bloodstream forms of Trypanosoma
      brucei rhodesiense and for cytotoxicity against the mammalian cell line L6.
      Vernodalin (2) was the most active compound with an IC50 value of 0.16 uM and a
      selectivity index of 35. Its closely related congener 11beta,13-dihydrovernodalin
      (3) registered an IC50 value of 1.1 uM and a selectivity index of 4.2.

PMID- 29382041
TI  - Association of Circulating Vitamin E (alpha- and gamma-Tocopherol) Levels with
      Gallstone Disease.
AB  - In addition to well-established risk factors like older age, female gender, and
      adiposity, oxidative stress may play a role in the pathophysiology of gallstone
      disease. Since vitamin E exerts important anti-oxidative functions, we
      hypothesized that circulating vitamin E levels might be inversely associated with
      prevalence of gallstone disease. In a cross-sectional study, we measured plasma
      levels of alpha- and gamma-tocopherol using high performance liquid
      chromatography in a community-based sample (582 individuals; median age 62 years;
      38.5% women). Gallstone disease status was assessed by ultrasound. Multivariable
      adjusted logistic regression models were used to estimate the association of
      circulating alpha- and gamma-tocopherol/cholesterol ratio levels with prevalent
      gallstone disease. Lower probabilities of having gallstone disease were observed
      in the top (compared to the bottom) tertile of the plasma alpha
      tocopherol/cholesterol ratio in multivariable-adjusted models (OR (Odds Ratio):
      0.31; 95% CI (Confidence Interval): 0.13-0.76). A lower probability of having
      gallstone disease was also observed for the gamma-tocopherol/cholesterol ratio,
      though the association did not reach statistical significance (OR: 0.77; 95% CI:
      0.35-1.69 for 3rd vs 1st tertile). In conclusion, our observations are consistent
      with the concept that higher vitamin E levels might protect from gallstone
      disease, a premise that needs to be further addressed in longitudinal studies.

PMID- 29382043
TI  - Phase Transformation Induced Self-Healing Behavior of Al-Ag Alloy.
AB  - Self-healing alloys are promising materials that can decrease the consequences of
      accidents. To detect crack formation in a material is simple task that can be
      performed by e.g., sonic or ultrasound detection, but it is not always possible
      to immediately replace the damaged parts. In this situation, it is very
      advantageous to have the chance to heal the crack during operation, which can be
      done e.g., by annealing. In this paper, self-healing behavior was proven by TEM
      (Transmission electron microscope) observation of crack healing after annealing.
      The crack was observed in the rapidly solidified Al-30Ag alloy with non
      equilibrium phase composition formed by a minor amount of Ag2Al and a
      supersaturated solid solution of Ag in an fcc-Al matrix (fcc = face centered
      cubic). After annealing at 450  degrees C, equilibrium phase composition was
      obtained by forming a higher amount of Ag2Al. This phase transformation did not
      allow the crack to be healed. Subsequent annealing at 550  degrees C caused
      recrystallization to a supersaturated solid solution of Ag in fcc-Al, followed by
      a return to the mixture of fcc-Al and Ag2Al by cooling, and this process was
      accompanied by the closing of the crack. This observation proved the self-healing
      possibilities of the Ag2Al phase. Practical application of this self-healing
      behavior could be achieved through the dispersion of fine Ag2Al particles in a
      structural material, which will enrich the material with self-healing properties.

PMID- 29382044
TI  - Large Area Nanoparticle Alignment by Chemical Lift-Off Lithography.
AB  - Nanoparticle alignment on the substrate attracts considerable attention due to
      its wide application in different fields, such as mechanical control, small size
      electronics, bio/chemical sensing, molecular manipulation, and energy harvesting.
      However, precise nanoparticle positioning and deposition control with high
      fidelity are still challenging. Herein, a straightforward strategy for high
      quality nanoparticle-alignment by chemical lift-off lithography (CLL) is
      demonstrated. This technique creates high resolution self-assembled monolayer
      (SAM) chemical patterns on gold substrates, enabling nanoparticle-selective
      deposition and precise alignment. The fabricated nanoparticle arrangement
      geometries and dimensions are well-controllable in a large area. With proper
      nanoparticle surface functionality control and adequate substrate molecular
      manipulation, well-defined nanoparticle arrays with single-particle-wide
      alignment resolution are achieved.

PMID- 29382042
TI  - Extracellular Influences: Molecular Subclasses and the Microenvironment in
      Pancreatic Cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent form of pancreatic
      cancer and carries the worst prognosis of all common cancers. Five-year survival
      rates have not surpassed 6% for some decades and this lack of improvement in
      outcome urges a better understanding of the PDAC-specific features which
      contribute to this poor result. One of the most defining features of PDAC known
      to contribute to its progression is the abundance of non-tumor cells and material
      collectively known as the stroma. It is now well recognized that the different
      non-cancer cell types, signalling molecules, and mechanical properties within a
      tumor can have both tumor-promoting as well as -inhibitory effects. However, the
      net effect of this intratumour heterogeneity is not well understood.
      Heterogeneity in the stromal makeup between patients is even less well
      established. Such intertumour heterogeneity is likely to be affected by the
      relative contributions of individual stromal constituents, but how these
      contributions exactly relate to existing classifications that demarcate
      intertumour heterogeneity in PDAC is not fully known. In this review, we give an
      overview of the available evidence by delineating the elements of the PDAC stroma
      and their contribution to tumour growth. We do so by interpreting the
      heterogeneity at the gene expression level in PDAC, and how stromal elements
      contribute to, or interconnect, with this.

PMID- 29382045
TI  - Interaction between Saikosaponin D, Paeoniflorin, and Human Serum Albumin.
AB  - Saikosaponin D (SSD) and paeoniflorin (PF) are the major active constituents of
      Bupleuri Radix and Paeonia lactiflora Pall, respectively, and have been widely
      used in China to treat liver and other diseases for many centuries. We explored
      the binding of SSD/PF to human serum albumin (HSA) by using
      fluorospectrophotometry, circular dichroism (CD) and molecular docking. Both SSD
      and PF produced a conformational change in HSA. Fluorescence quenching was
      accompanied by a blue shift in the fluorescence spectra. Co-binding of PF and SSD
      also induced quenching and a conformational change in HSA. The Stern-Volmer
      equation showed that quenching was dominated by static quenching. The binding
      constant for ternary interaction was below that for binary interaction. Site
      competitive experiments demonstrated that SSD/PF bound to site I (subdomain IIA)
      and site II (subdomain IIIA) in HSA. Analysis of thermodynamic parameters
      indicated that hydrogen bonding and van der Waals forces were mostly responsible
      for the binary association. Also, there was energy transfer upon binary
      interaction. Molecular docking supported the experimental findings in
      conformation, binding sites and binding forces.

PMID- 29382046
TI  - How Do We Study the Dynamic Structure of Unstructured Proteins: A Case Study on
      Nopp140 as an Example of a Large, Intrinsically Disordered Protein.
AB  - Intrinsically disordered proteins (IDPs) represent approximately 30% of the human
      genome and play key roles in cell proliferation and cellular signaling by
      modulating the function of target proteins via protein-protein interactions. In
      addition, IDPs are involved in various human disorders, such as cancer,
      neurodegenerative diseases, and amyloidosis. To understand the underlying
      molecular mechanism of IDPs, it is important to study their structural features
      during their interactions with target proteins. However, conventional biochemical
      and biophysical methods for analyzing proteins, such as X-ray crystallography,
      have difficulty in characterizing the features of IDPs because they lack an
      ordered three-dimensional structure. Here, we present biochemical and biophysical
      studies on nucleolar phosphoprotein 140 (Nopp140), which mostly consists of
      disordered regions, during its interaction with casein kinase 2 (CK2), which
      plays a central role in cell growth. Surface plasmon resonance and electron
      paramagnetic resonance studies were performed to characterize the interaction
      between Nopp140 and CK2. A single-molecule fluorescence resonance energy transfer
      study revealed conformational change in Nopp140 during its interaction with CK2.
      These studies on Nopp140 can provide a good model system for understanding the
      molecular function of IDPs.

PMID- 29382048
TI  - A Molecular Method for the Identification of Honey Bee Subspecies Used by
      Beekeepers in Russia.
AB  - Apis mellifera L. includes several recognized subspecies that differ in their
      biological properties and agricultural characteristics. Distinguishing between
      honey bee subspecies is complicated. We analyzed the Folmer region of the COX1
      gene in honey bee subspecies cultivated at bee farms in Russia and identified
      subspecies-specific SNPs. DNA analysis revealed two clearly distinct haplogroups
      in A. melliferamellifera. The first one was characterized by multiple cytosine
      thymine (thymine-cytosine) transitions, one adenine-guanine substitution, and one
      thymine-adenine substitution. The nucleotide sequence of the second haplogroup
      coincided with sequences from other subspecies, except the unique C/A SNP at
      position 421 of the 658-bp Folmer region. A. melliferacarnica and A.
      melliferacarpatica could be distinguished from A. melliferamellifera and A.
      melliferacaucasica by the presence of the A/G SNP at position 99 of the 658-bp
      Folmer region. The G/A SNP at position 448 was typical for A. melliferacarnica.
      A. melliferacaucasicaCOX1 sequence lacked all the above-mentioned sites. We
      developed a procedure for rapid identification of honey bee subspecies by PCR
      with restriction fragment length polymorphism (RFLP) using mutagenic primers. The
      developed molecular method for honey bee subspecies identification is fast and
      inexpensive.

PMID- 29382047
TI  - Reviewing the Utility of EUS FNA to Advance Precision Medicine in Pancreatic
      Cancer.
AB  - Advanced pancreatic cancer (PC) is an aggressive malignancy with few effective
      therapeutic options. While the evolution of precision medicine in recent decades
      has changed the treatment landscape in many cancers, at present no targeted
      therapies are used in the routine management of PC. Only a minority of patients
      with PC present with surgically resectable disease, and in the remainder
      obtaining high quality biopsy material for both diagnosis and molecular testing
      can prove challenging. Endoscopic ultrasound-guided fine needle aspiration (EUS
      FNA) is a widely used diagnostic procedure in PC, and allows tumour sampling in
      patients with both early and late stage disease. This review will provide an
      update on the role of EUS FNA as a diagnostic tool, as well as a source of
      genetic material which can be used both for molecular analysis and for the
      creation of valuable preclinical disease models. We will also consider relevant
      clinical applications of EUS FNA in the management of PC, and the path towards
      bringing precision medicine closer to the clinic in this challenging disease.

PMID- 29382049
TI  - Nicotinic Acid Long-Term Effectiveness in a Patient with Bipolar Type II
      Disorder: A Case of Vitamin Dependency.
AB  - Nicotinic acid (NA), often called niacin, a form of vitamin B3, is a water
      soluble nutrient found in animal and vegetarian foods. Vitamin B3 for healthy
      people is considered to be needed in doses of less than 20 mg daily. In higher
      doses, NA has been described to be beneficial in some patients with psychiatric
      disorders. This report describes a male patient with bipolar type II disorder who
      for many years had been treated with lithium and other medications applied in
      affective disorders. These pharmacological drugs had beneficial effects but were
      at times insufficient. When the patient was prescribed NA, he experienced a
      comparatively strong effect. Slowly it was discovered that the patient could
      lower and cease all medications except NA. For over 11 years he has been stable
      and calm with NA and currently takes 1 g three times daily. When not taking NA,
      he consistently became anxious and depressed within 2-3 days. The resumption of
      NA resulted in a normal state usually within 1 day. This finding has been
      described as a vitamin dependency. The paper discusses possible mechanisms for
      the effect of NA in this patient. Further studies are needed to investigate the
      prevalence of vitamin B3 dependency and the biochemical explanations for this
      phenomenon.

PMID- 29382050
TI  - Wearable Intrinsically Soft, Stretchable, Flexible Devices for Memories and
      Computing.
AB  - A recent trend in the development of high mass consumption electron devices is
      towards electronic textiles (e-textiles), smart wearable devices, smart clothes,
      and flexible or printable electronics. Intrinsically soft, stretchable, flexible,
      Wearable Memories and Computing devices (WMCs) bring us closer to sci-fi
      scenarios, where future electronic systems are totally integrated in our everyday
      outfits and help us in achieving a higher comfort level, interacting for us with
      other digital devices such as smartphones and domotics, or with analog devices,
      such as our brain/peripheral nervous system. WMC will enable each of us to
      contribute to open and big data systems as individual nodes, providing real-time
      information about physical and environmental parameters (including air pollution
      monitoring, sound and light pollution, chemical or radioactive fallout alert,
      network availability, and so on). Furthermore, WMC could be directly connected to
      human brain and enable extremely fast operation and unprecedented interface
      complexity, directly mapping the continuous states available to biological
      systems. This review focuses on recent advances in nanotechnology and materials
      science and pays particular attention to any result and promising technology to
      enable intrinsically soft, stretchable, flexible WMC.

PMID- 29382052
TI  - Exploring the Gaps in Practical Ethical Guidance for Animal Welfare
      Considerations of Field Interventions and Innovations Targeting Dogs and Cats.
AB  - Domestic dogs (Canis lupus familiaris) and cats (Felis silvestris catus) are
      common species targeted by nongovernmental or intergovernmental organizations,
      veterinarians and government agencies worldwide, for field interventions (e.g.,
      population management, rabies vaccination programs) or innovations (e.g.,
      development of technologies or pharmaceuticals to improve animal welfare). We
      have a moral responsibility to ensure that the conduct of this work is humane for
      dogs or cats, and to consider the human communities in which the animals live.
      Ethical review is widely accepted as being integral to responsible practice, and
      it is fundamental to good science that underpins innovation. Despite the
      necessity of field interventions or innovations to advance the welfare of
      individuals or populations of animals, we found a lack of specific guidance and
      review processes to help navigate ethical dilemmas surrounding the conduct of
      such work. This can be detrimental to the wellbeing of animals and their human
      communities. Here we identify the gaps in existing ethical frameworks
      (specifically application of Reduction and Refinement principles, challenges of
      obtaining meaningful informed consent with variations in the quality of human
      animal relationships, and limited resources regarding considerations of local
      stakeholders), and outline the need for additional tools to promote ethical
      conduct in the field.

PMID- 29382053
TI  - Fuzzy Traffic Control with Vehicle-to-Everything Communication.
AB  - Traffic signal control (TSC) with vehicle-to everything (V2X) communication can
      be a very efficient solution to traffic congestion problem. Ratio of vehicles
      equipped with V2X communication capability in the traffic to the total number of
      vehicles (called penetration rate PR) is still low, thus V2X based TSC systems
      need to be supported by some other mechanisms. PR is the major factor that
      affects the quality of TSC process along with the evaluation interval. Quality of
      the TSC in each direction is a function of overall TSC quality of an
      intersection. Hence, quality evaluation of each direction should follow the
      evaluation of the overall intersection. Computational intelligence, more
      specifically swarm algorithm, has been recently used in this field in a European
      Framework Program FP7 supported project called COLOMBO. In this paper, using
      COLOMBO framework, further investigations have been done and two new
      methodologies using simple and fuzzy logic have been proposed. To evaluate the
      performance of our proposed methods, a comparison with COLOMBOs approach has been
      realized. The results reveal that TSC problem can be solved as a logical problem
      rather than an optimization problem. Performance of the proposed approaches is
      good enough to be suggested for future work under realistic scenarios even under
      low PR.

PMID- 29382054
TI  - Investigation of the Microstructure Evolution and Deformation Mechanisms of a Mg
      Zn-Zr-RE Twin-Roll-Cast Magnesium Sheet by In-Situ Experimental Techniques.
AB  - Twin roll casting (TRC), with a relatively fast solidification rate, is an
      excellent production method with promising potential for producing wrought semi
      or final Mg alloy products that can often suffer from poor formability. We
      investigate in this study the effect of the TRC method and the subsequent heat
      treatment on the microstructure and deformation mechanisms in Mg-Zn-Zr-Nd alloy
      deformed at room temperature using the in-situ neutron diffraction and acoustic
      emission techniques and ex-situ texture measurement and microscopy, respectively.
      Although a higher work hardening is observed in the rolling direction due to the
      more intensive <a>-type dislocation activity, the difference in the mechanical
      properties of the specimens deformed in the RD and TD directions is small in the
      as-rolled condition. An additional heat treatment results in recrystallization
      and significant anisotropy in the deformation. Due to the easier activation of
      the extension twinning in the TD given by texture, the yield stress in the TD is
      approximately 40% lower than that in the RD.

PMID- 29382051
TI  - Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds.
AB  - Many naturally occurring substances, traditionally used in popular medicines
      around the world, contain the coumarin moiety. Coumarin represents a privileged
      scaffold for medicinal chemists, because of its peculiar physicochemical
      features, and the versatile and easy synthetic transformation into a large
      variety of functionalized coumarins. As a consequence, a huge number of coumarin
      derivatives have been designed, synthesized, and tested to address many
      pharmacological targets in a selective way, e.g., selective enzyme inhibitors,
      and more recently, a number of selected targets (multitarget ligands) involved in
      multifactorial diseases, such as Alzheimer's and Parkinson's diseases. In this
      review an overview of the most recent synthetic pathways leading to mono- and
      polyfunctionalized coumarins will be presented, along with the main biological
      pathways of their biosynthesis and metabolic transformations. The many existing
      and recent reviews in the field prompted us to make some drastic selections, and
      therefore, the review is focused on monoamine oxidase, cholinesterase, and
      aromatase inhibitors, and on multitarget coumarins acting on selected targets of
      neurodegenerative diseases.

PMID- 29382055
TI  - Early-Life Iron Deficiency Reduces Brain Iron Content and Alters Brain Tissue
      Composition Despite Iron Repletion: A Neuroimaging Assessment.
AB  - Early-life iron deficiency has lifelong influences on brain structure and
      cognitive function, however characterization of these changes often requires
      invasive techniques. There is a need for non-invasive assessment of early-life
      iron deficiency with potential to translate findings to the human clinical
      setting. In this study, 28 male pigs were provided either a control diet (CONT; n
      = 14; 23.5 mg Fe/L milk replacer) or an iron-deficient diet (ID; n = 14; 1.56 mg
      Fe/L milk replacer) for phase 1 of the study, from postnatal day (PND) 2 until
      32. Twenty pigs (n = 10/diet from phase 1 were used in phase 2 of the study from
      PND 33 to 61, where all pigs were provided a common iron-sufficient diet,
      regardless of their phase 1 dietary iron status. All pigs were subjected to
      magnetic resonance imaging at PND 32 and again at PND 61, and quantitative
      susceptibility mapping was used to assess brain iron content at both imaging time
      points. Data collected on PND 61 were analyzed using voxel-based morphometry and
      tract-based spatial statistics to determine tissue concentration difference and
      white matter tract integrity, respectively. Quantitative susceptibility mapping
      outcomes indicated reduced iron content in the pons, medulla, cerebellum, left
      cortex, and left hippocampus of ID pigs compared with CONT pigs, regardless of
      imaging time-point. In contrast, iron contents were increased in the olfactory
      bulbs of ID pigs compared with CONT pigs. Voxel-based morphometric analysis
      indicated increased grey and white matter concentrations in CONT pigs compared
      with ID pigs that were evident at PND 61. Differences in tissue concentrations
      were predominately located in cortical tissue as well as the cerebellum,
      thalamus, caudate, internal capsule, and hippocampi. Tract-based spatial
      statistics indicated increased fractional anisotropy values along subcortical
      white matter tracts in CONT pigs compared with ID pigs that were evident on PND
      61. All described differences were significant at p <= 0.05. Results from this
      study indicate that neuroimaging can sensitively detect structural and
      physiological changes due to early-life iron deficiency, including grey and white
      matter volumes, iron contents, as well as reduced subcortical white matter
      integrity, despite a subsequent period of dietary iron repletion.

PMID- 29382056
TI  - Identification of Genetic Regions Associated with Scrotal Hernias in a Commercial
      Swine Herd.
AB  - In this paper, we have used two approaches to detect genetic associations with
      scrotal hernias in commercial pigs. Firstly, we have investigated the effects of
      runs of homozygosity (ROH) with the appearance of scrotal hernias, followed by a
      Genome Wide Association Study (GWAS). The phenotype classification was based on
      visual appearance of scrotal hernias. Each affected animal was matched to a
      healthy control from the same pen. In the total, 68 animals were genotyped using
      the Porcine SNP60 Beadchip, out of those, 41 animals had the presence of hernias
      and 27 were healthy animals. Fifteen animals were removed from the analysis due
      to differences in genetic background, leaving 18 healthy animals and 35 piglets
      with scrotal hernia. Further, the detection of extended haplotypes shared ROH
      were conducted for health (control) and affected (case) animals and a permutation
      test was used to test whether the ROH segments were more frequent in case/case
      pairs than non-case/case pairs. Using the ROH, we have identified an association
      (p = 0.019) on chromosome 2(SSC2) being segregated on animals with the presence
      of scrotal hernias. Using a GWAS, a region composed by 3 SNPs on the sexual
      chromosome X (SSCX) were associated with scrotal hernias (p < 1.6 * 10-5), this
      region harbors the Androgen Receptor Gene (AR).

PMID- 29382057
TI  - Impact of Thermal Degradation of Cyanidin-3-O-Glucoside of Haskap Berry on
      Cytotoxicity of Hepatocellular Carcinoma HepG2 and Breast Cancer MDA-MB-231
      Cells.
AB  - Cyanidin-3-O-glucoside (C3G), the predominant anthocyanin in haskap berries
      (Lonicera caerulea L.), possesses antioxidant and many other biological
      activities. This study investigated the impact of temperature and pH on the
      degradation of the C3G-rich haskap fraction. The effect of the thermal
      degradation products on the viability of hepatocellular carcinoma HepG2 and
      breast cancer MDA-MB-231 cells was also studied in vitro. Using column
      chromatography, the C3G-rich fraction was isolated from acetone extracts of
      haskap berries. The C3G stability in these fractions was studied under elevated
      temperatures (70  degrees C and 90  degrees C) at three different pH values (2.5,
      4, and 7) by monitoring the concentration of C3G and its major degradation
      products, protocatechuic acid (PCA) and phloroglucinaldehyde (PGA), using liquid
      chromatography mass spectrometry. Significant degradation of C3G was observed at
      elevated temperatures and at neutral pH. Conversely, the PCA and PGA
      concentration increased at higher pH and temperature. Similar to C3G, neutral pH
      also has a prominent effect on the degradation of PGA, which is further
      accelerated by heating. The C3G-rich fraction exhibited dose-dependent inhibitory
      effects on cell metabolic activity when the HepG2 cells were exposed for 48 h.
      Interestingly, PGA but not PCA exhibited cytotoxic effects against both MDA-MB
      231 and HepG2 cells. The results suggest that thermal food processing of haskap
      could influence its biological properties due to the degradation of C3G.

PMID- 29382058
TI  - Comparing Two Independent Satellite-Based Algorithms for Detecting and Tracking
      Ash Clouds by Using SEVIRI Sensor.
AB  - The Eyjafjallajokull (Iceland) volcanic eruption of April-May 2010 caused
      unprecedented air-traffic disruption in Northern Europe, revealing some important
      weaknesses of current operational ash-monitoring and forecasting systems and
      encouraging the improvement of methods and procedures for supporting the
      activities of Volcanic Ash Advisory Centers (VAACs) better. In this work, we
      compare two established satellite-based algorithms for ash detection, namely
      RSTASH and the operational London VAAC method, both exploiting sensor data of the
      spinning enhanced visible and infrared imager (SEVIRI). We analyze similarities
      and differences in the identification of ash clouds during the different phases
      of the Eyjafjallajokull eruption. The work reveals, in some cases, a certain
      complementary behavior of the two techniques, whose combination might improve the
      identification of ash-affected areas in specific conditions. This is indicated by
      the quantitative comparison of the merged SEVIRI ash product, achieved
      integrating outputs of the RSTASH and London VAAC methods, with independent
      atmospheric infrared sounder (AIRS) DDA (dust-detection algorithm) observations.

PMID- 29382061
TI  - Securing Cooperative Spectrum Sensing Against Collusive SSDF Attack using XOR
      Distance Analysis in Cognitive Radio Networks.
AB  - Cooperative spectrum sensing (CSS) is considered as a powerful approach to
      improve the utilization of scarce spectrum resources. However, if CSS assumes
      that all secondary users (SU) are honest, it may offer opportunities for
      attackers to conduct a spectrum sensing data falsification (SSDF) attack. To
      suppress such a threat, recent efforts have been made to develop trust
      mechanisms. Currently, some attackers can collude with each other to form a
      collusive clique, and thus not only increase the power of SSDF attack but also
      avoid the detection of a trust mechanism. Noting the duality of sensing data, we
      propose a defense scheme called XDA from the perspective of XOR distance analysis
      to suppress a collusive SSDF attack. In the XDA scheme, the XOR distance
      calculation in line with the type of "0" and "1" historical sensing data is used
      to measure the similarity between any two SUs. Noting that collusive SSDF
      attackers hold high trust value and the minimum XOR distance, the algorithm to
      detect collusive SSDF attackers is designed. Meanwhile, the XDA scheme can
      perfect the trust mechanism to correct collusive SSDF attackers' trust value.
      Simulation results show that the XDA scheme can enhance the accuracy of trust
      evaluation, and thus successfully reduce the power of collusive SSDF attack
      against CSS.

PMID- 29382059
TI  - Nucleus Accumbens Deep Brain Stimulation in Patients with Substance Use Disorders
      and Delay Discounting.
AB  - Deep brain stimulation (DBS) of the nucleus accumbens (NAc) shows first promising
      results in patients with severe substance use disorder (SUD), a patient group
      known to have deficits in self-control. One facet of self-control is the ability
      to forego smaller sooner rewards in favor of larger later rewards (delay
      discounting, DD). The NAc has been suggested to integrate motivational
      information to guide behavior while the consequences of NAc-DBS on DD are
      unknown. To this end, nine patients with SUD performed a DD task with DBS on and
      after a 24 h DBS off period. Furthermore, 18 healthy controls were measured to
      assess possible alterations in DD in patients with SUD. Our findings implicate
      that DD was not significantly modulated by NAc-DBS and also that patients with
      SUD did not differ from healthy controls. While null results must be interpreted
      with caution, the commonly observed association of impaired DD in SUD might
      suggest a long-term effect of NAc-DBS that was not sufficiently modulated by a 24
      h DBS off period.

PMID- 29382060
TI  - Predicting the Effect of Single and Multiple Mutations on Protein Structural
      Stability.
AB  - Predicting how a point mutation alters a protein's stability can guide
      pharmaceutical drug design initiatives which aim to counter the effects of
      serious diseases. Conducting mutagenesis studies in physical proteins can give
      insights about the effects of amino acid substitutions, but such wet-lab work is
      prohibitive due to the time as well as financial resources needed to assess the
      effect of even a single amino acid substitution. Computational methods for
      predicting the effects of a mutation on a protein structure can complement wet
      lab work, and varying approaches are available with promising accuracy rates. In
      this work we compare and assess the utility of several machine learning methods
      and their ability to predict the effects of single and double mutations. We in
      silico generate mutant protein structures, and compute several rigidity metrics
      for each of them. We use these as features for our Support Vector Regression
      (SVR), Random Forest (RF), and Deep Neural Network (DNN) methods. We validate the
      predictions of our in silico mutations against experimental Delta Delta G
      stability data, and attain Pearson Correlation values upwards of 0.71 for single
      mutations, and 0.81 for double mutations. We perform ablation studies to assess
      which features contribute most to a model's success, and also introduce a voting
      scheme to synthesize a single prediction from the individual predictions of the
      three models.

PMID- 29382062
TI  - Giving Voice to the Medically Under-Served: A Qualitative Co-Production Approach
      to Explore Patient Medicine Experiences and Improve Services to Marginalized
      Communities.
AB  - BACKGROUND: With an aging population, the appropriate, effective and safe use of
      medicines is a global health priority. However, "'medically under-served"
      patients continue to experience significant inequalities around access to
      healthcare services. AIM: This study forms part of a wider project to co-develop
      and evaluate a digital educational intervention for community pharmacy. The aim
      of this paper is to explore the medicine needs of patients from marginalized
      communities and suggest practical way on how services could be better tailored to
      their requirements. METHOD: Following ethical approval, qualitative data was
      gathered from: (1) workshops with patients and professionals (n = 57 attendees);
      and (2) qualitative semi-structured interviews (10 patients and 10 pharmacists).
      RESULTS: Our findings revealed that patients from marginalized communities
      reported poor management of their medical conditions and significant problems
      with adherence to prescribed medicines. Their experience of pharmacy services was
      found to be variable with many experiencing discrimination or disadvantage as a
      result of their status. DISCUSSION: This study highlights the plight of medically
      under-served communities and the need for policy makers to tailor services to an
      individual's needs and circumstances. Furthermore, patients and professionals can
      work in collaboration using a co-production approach to develop educational
      interventions for pharmacy service improvements.

PMID- 29382063
TI  - An Interdigital Electrode Probe for Detection, Localization and Evaluation of
      Surface Notch-Type Damage in Metals.
AB  - Available microwave notch-type damage detection sensors are typically based on
      monitoring frequency shift or magnitude changes. However, frequency shift testing
      needs sweep-frequency data that make scanning detection becomes difficult and
      time-consuming. This work presents a microwave near-field nondestructive testing
      sensor for detecting sub-millimeter notch-type damage detection in metallic
      surfaces. The sensor is loaded with an interdigital electrode element in an open
      ended coaxial. It is simple to fabricate and inexpensive, as it is etched on the
      RC4003 patch by using printed circuit board technology. The detection is achieved
      by monitoring changes in reflection amplitude, which is caused by perturbing the
      electromagnetic field around the interdigital structure. The proposed sensor was
      tested on a metallic plate with different defects, and the experimental results
      indicated that the interdigital electrode probe can determine the orientation,
      localization and dimension of surface notch-type damage.

PMID- 29382064
TI  - Human Identification by Cross-Correlation and Pattern Matching of Personalized
      Heartbeat: Influence of ECG Leads and Reference Database Size.
AB  - Human identification (ID) is a biometric task, comparing single input sample to
      many stored templates to identify an individual in a reference database. This
      paper aims to present the perspectives of personalized heartbeat pattern for
      reliable ECG-based identification. The investigations are using a database with
      460 pairs of 12-lead resting electrocardiograms (ECG) with 10-s durations
      recorded at time-instants T1 and T2 > T1 + 1 year. Intra-subject long-term ECG
      stability and inter-subject variability of personalized PQRST (500 ms) and QRS
      (100 ms) patterns is quantified via cross-correlation, amplitude ratio and
      pattern matching between T1 and T2 using 7 features * 12-leads. Single and multi
      lead ID models are trained on the first 230 ECG pairs. Their validation on 10,
      20, ... 230 reference subjects (RS) from the remaining 230 ECG pairs shows: (i)
      two best single-lead ID models using lead II for a small population RS = (10-140)
      with identification accuracy AccID = (89.4-67.2)% and aVF for a large population
      RS = (140-230) with AccID = (67.2-63.9)%; (ii) better performance of the 6-lead
      limb vs. the 6-lead chest ID model-(91.4-76.1)% vs. (90.9-70)% for RS = (10-230);
      (iii) best performance of the 12-lead ID model-(98.4-87.4)% for RS = (10-230).
      The tolerable reference database size, keeping AccID > 80%, is RS = 30 in the
      single-lead ID scenario (II); RS = 50 (6 chest leads); RS = 100 (6 limb leads),
      RS > 230-maximal population in this study (12-lead ECG).

PMID- 29382065
TI  - Electrospun Fibers as a Dressing Material for Drug and Biological Agent Delivery
      in Wound Healing Applications.
AB  - Wound healing is a complex tissue regeneration process that promotes the growth
      of new tissue to provide the body with the necessary barrier from the outside
      environment. In the class of non-healing wounds, diabetic wounds, and ulcers,
      dressing materials that are available clinically (e.g., gels and creams) have
      demonstrated only a slow improvement with current available technologies. Among
      all available current technologies, electrospun fibers exhibit several
      characteristics that may provide novel replacement dressing materials for the
      above-mentioned wounds. Therefore, in this review, we focus on recent
      achievements in electrospun drug-eluting fibers for wound healing applications.
      In particular, we review drug release, including small molecule drugs, proteins
      and peptides, and gene vectors from electrospun fibers with respect to wound
      healing. Furthermore, we provide an overview on multifunctional dressing
      materials based on electrospun fibers, including those that are capable of
      achieving wound debridement and wound healing simultaneously as well as multi
      drugs loading/types suitable for various stages of the healing process. Our
      review provides important and sufficient information to inform the field in
      development of fiber-based dressing materials for clinical treatment of non
      healing wounds.

PMID- 29382067
TI  - Relationship between the Size of the Samples and the Interpretation of the
      Mercury Intrusion Results of an Artificial Sandstone.
AB  - Mercury intrusion porosimetry (MIP) measurements are widely used to determine
      pore throat size distribution (PSD) curves of porous materials. The pore throat
      size of porous materials has been used to estimate their compressive strength and
      air permeability. However, the effect of sample size on the determined PSD curves
      is often overlooked. In pursuit of a better understanding of the effect of sample
      size on mercury intrusion into porous materials, a combined experimental and
      numerical approach was applied. Quartz sand and epoxy resin were mixed to form
      artificial sandstone. Digital microstructures of the sandstone were obtained by
      using X-ray computed tomography (CT scan) technique. PSD curves of the artificial
      sandstone with different sample sizes were determined both by MIP measurement and
      by simulation of mercury intrusion (i.e., MIP simulation). Percolation analysis
      was performed on mercury-intruded pores in the digital microstructures. The PSD
      curves determined both by MIP measurements and by MIP simulations show that there
      was a significant effect of sample size on mercury intrusion before percolation
      of mercury-intruded pores. The effect of sample size decreased with the
      increasing pressure. After the mercury-intruded pores percolated through the
      samples, the effect of sample size on mercury intrusion became minor. The pore
      throat size of the artificial sandstone was used to estimate the air permeability
      using the relation proposed in the literature. The calculated air permeability of
      the smaller sandstone sample was higher. However, in principle, the air
      permeability of sandstone samples should be independent of the sample size. Two
      main conclusions can be drawn: (1) a fixed sample size should be used in MIP
      measurements or MIP simulation so that the PSD curves of different samples can be
      properly compared, (2) sample size needs to be considered when the pore throat
      size determined by MIP measurement is used for estimating air permeability.

PMID- 29382066
TI  - Resistance to the Antiproliferative In Vitro Effect of PI3K-Akt-mTOR Inhibition
      in Primary Human Acute Myeloid Leukemia Cells Is Associated with Altered Cell
      Metabolism.
AB  - Constitutive signaling through the phosphatidylinositol-3-kinase-Akt-mechanistic
      target of rapamycin (PI3K-Akt-mTOR) pathway is present in acute myeloid leukemia
      (AML) cells. However, AML is a heterogeneous disease, and we therefore
      investigated possible associations between cellular metabolism and sensitivity to
      PI3K-Akt-mTOR pathway inhibitors. We performed non-targeted metabolite profiling
      to compare the metabolome differences of primary human AML cells derived from
      patients susceptible or resistant to the in vitro antiproliferative effects of
      mTOR and PI3K inhibitors. In addition, the phosphorylation status of 18 proteins
      involved in PI3K-Akt-mTOR signaling and the effect of the cyclooxygenase
      inhibitor indomethacin on their phosphorylation status was investigated by flow
      cytometry. Strong antiproliferative effects by inhibitors were observed only for
      a subset of patients. We compared the metabolite profiles for responders and non
      responders towards PI3K-mTOR inhibitors, and 627 metabolites could be detected.
      Of these metabolites, 128 were annotated and 15 of the annotated metabolites
      differed significantly between responders and non-responders, including
      metabolites involved in energy, amino acid, and lipid metabolism. To conclude,
      leukemia cells that are susceptible or resistant to PI3K-Akt-mTOR inhibitors
      differ in energy, amino acid, and arachidonic acid metabolism, and modulation of
      arachidonic acid metabolism alters the activation of mTOR and its downstream
      mediators.

PMID- 29382068
TI  - Higher Cytopathic Effects of a Zika Virus Brazilian Isolate from Bahia Compared
      to a Canadian-Imported Thai Strain.
AB  - Zika virus (ZIKV) is an emerging pathogen from the Flaviviridae family. It
      represents a significant threat to global health due to its neurological and
      fetal pathogenesis (including microcephaly and congenital malformations), and its
      rapid dissemination across Latin America in recent years. The virus has spread
      from Africa to Asia, the Pacific islands and the Americas with limited knowledge
      about the pathogenesis associated with infection in recent years. Herein, we
      compared the ability of the Canadian-imported Thai strain PLCal_ZV and the
      Brazilian isolate HS-2015-BA-01 from Bahia to produce infectious ZIKV particles
      and cytopathic effects in a cell proliferation assay. We also compared the
      intracellular viral RNA accumulation of the two strains by quantitative RT-PCR
      (reverse transcription polymerase chain reaction) analyses. Our observations show
      that HS-2015-BA-01 is more cytopathic than PLCal_ZV in proliferation assays in
      Vero, Human Embryonic Kidney HEK 293T and neuroblastoma SH-SY5Y cells.
      Quantitative RT-PCR shows that the level of viral RNA is higher with HS-2015-BA
      01 than with PLCal_ZV in two cell lines, but similar in a neuroblastoma cell
      line. The two strains have 13 amino acids polymorphisms and we analyzed their
      predicted protein secondary structure. The increased cytopathicity and RNA
      accumulation of the Brazilian ZIKV isolate compared to the Thai isolate could
      contribute to the increased pathogenicity observed during the Brazilian epidemic.

PMID- 29382069
TI  - Diets Rich in Fruits and Vegetables Are Associated with Lower Cardiovascular
      Disease Risk in Adolescents.
AB  - Obesity and cardiovascular disease (CVD) risk are public health concerns in
      adolescents, yet few studies have examined the association of their diet to CVD
      risk factors. This study investigated associations between diet, body mass index
      (BMI), waist circumference (WC), blood pressure (BP), and blood lipids in 163 16
      17 year olds. Diet recall data were converted into Healthy Eating Index-2010
      (HEI) to assess diet quality. Differences in diet between groups with normal or
      obese BMI, normal or hypertensive BP, and normal or altered lipids were
      determined. Associations between diet and BMI, WC, BP, and lipids, controlling
      for race, gender, and socioeconomic status, were examined. Mean HEI was 49.2 (+/
      12.0), with no differences observed between groups. HEI was not associated with
      any CVD risk. Sweetened beverage consumption was higher in obese adolescents, and
      positively related to total cholesterol (TC). Fruit intake was negatively related
      to BMI and diastolic BP. Total vegetable intake was negatively related to
      systolic BP. Greens and beans were negatively related to TC and LDL. Whole grains
      were negatively related to HDL. This research suggests a cardioprotective effect
      of diets rich in fruits and vegetables, as well as low in sweetened beverages in
      adolescents.

PMID- 29382070
TI  - Human Microbiome Acquisition and Bioinformatic Challenges in Metagenomic Studies.
AB  - The study of the human microbiome has become a very popular topic. Our microbial
      counterpart, in fact, appears to play an important role in human physiology and
      health maintenance. Accordingly, microbiome alterations have been reported in an
      increasing number of human diseases. Despite the huge amount of data produced to
      date, less is known on how a microbial dysbiosis effectively contributes to a
      specific pathology. To fill in this gap, other approaches for microbiome study,
      more comprehensive than 16S rRNA gene sequencing, i.e., shotgun metagenomics and
      metatranscriptomics, are becoming more widely used. Methods standardization and
      the development of specific pipelines for data analysis are required to
      contribute to and increase our understanding of the human microbiome relationship
      with health and disease status.

PMID- 29382071
TI  - Quality of Life (QoL) Survey in Hong Kong: Understanding the Importance of
      Housing Environment and Needs of Residents from Different Housing Sectors.
AB  - This study presents a Quality of Life (QoL) survey to understand the influence of
      the housing environment and needs of residents from different housing sectors.
      The research focuses on Hong Kong where living conditions have become the main
      affect for people's QoL. Through a household survey using a standard instrument
      "Word Health Organisation (WHO) Quality of Life-BREF", the article found that
      among the four WHO QoL domains (Physical Health, Psychological Health, Social
      Relations And Environment), Environment, particularly its constitute aspect
      housing environment was the most influential factor for overall quality of life
      for the public rental housing sector where low-income people live. This research
      also found that different groups of people have differing needs of their housing
      environments: the low-income group needs better location and privacy while the
      medium and high-income groups need better architectural quality. Based on
      differentiating their needs and wants, this research argues for prioritizing the
      low-income group's needs for effectively improving their QoL.

PMID- 29382072
TI  - Self-Learning Power Control in Wireless Sensor Networks.
AB  - Current trends in interconnecting myriad smart objects to monetize on Internet of
      Things applications have led to high-density communications in wireless sensor
      networks. This aggravates the already over-congested unlicensed radio bands,
      calling for new mechanisms to improve spectrum management and energy efficiency,
      such as transmission power control. Existing protocols are based on simplistic
      heuristics that often approach interference problems (i.e., packet loss, delay
      and energy waste) by increasing power, leading to detrimental results. The scope
      of this work is to investigate how machine learning may be used to bring wireless
      nodes to the lowest possible transmission power level and, in turn, to respect
      the quality requirements of the overall network. Lowering transmission power has
      benefits in terms of both energy consumption and interference. We propose a
      protocol of transmission power control through a reinforcement learning process
      that we have set in a multi-agent system. The agents are independent learners
      using the same exploration strategy and reward structure, leading to an overall
      cooperative network. The simulation results show that the system converges to an
      equilibrium where each node transmits at the minimum power while respecting high
      packet reception ratio constraints. Consequently, the system benefits from low
      energy consumption and packet delay.

PMID- 29382073
TI  - Multi-Feature Classification of Multi-Sensor Satellite Imagery Based on Dual
      Polarimetric Sentinel-1A, Landsat-8 OLI, and Hyperion Images for Urban Land-Cover
      Classification.
AB  - This paper focuses on evaluating the ability and contribution of using
      backscatter intensity, texture, coherence, and color features extracted from
      Sentinel-1A data for urban land cover classification and comparing different
      multi-sensor land cover mapping methods to improve classification accuracy. Both
      Landsat-8 OLI and Hyperion images were also acquired, in combination with
      Sentinel-1A data, to explore the potential of different multi-sensor urban land
      cover mapping methods to improve classification accuracy. The classification was
      performed using a random forest (RF) method. The results showed that the optimal
      window size of the combination of all texture features was 9 * 9, and the optimal
      window size was different for each individual texture feature. For the four
      different feature types, the texture features contributed the most to the
      classification, followed by the coherence and backscatter intensity features; and
      the color features had the least impact on the urban land cover classification.
      Satisfactory classification results can be obtained using only the combination of
      texture and coherence features, with an overall accuracy up to 91.55% and a kappa
      coefficient up to 0.8935, respectively. Among all combinations of Sentinel-1A
      derived features, the combination of the four features had the best
      classification result. Multi-sensor urban land cover mapping obtained higher
      classification accuracy. The combination of Sentinel-1A and Hyperion data
      achieved higher classification accuracy compared to the combination of Sentinel
      1A and Landsat-8 OLI images, with an overall accuracy of up to 99.12% and a kappa
      coefficient up to 0.9889. When Sentinel-1A data was added to Hyperion images, the
      overall accuracy and kappa coefficient were increased by 4.01% and 0.0519,
      respectively.

PMID- 29382074
TI  - Evidence for Dietary Fibre Modification in the Recovery and Prevention of
      Reoccurrence of Acute, Uncomplicated Diverticulitis: A Systematic Literature
      Review.
AB  - In practice, nutrition recommendations vary widely for inpatient and discharge
      management of acute, uncomplicated diverticulitis. This systematic review aims to
      review the evidence and develop recommendations for dietary fibre modifications,
      either alone or alongside probiotics or antibiotics, versus any comparator in
      adults in any setting with or recently recovered from acute, uncomplicated
      diverticulitis. Intervention and observational studies in any language were
      located using four databases until March 2017. The Cochrane Risk of Bias tool and
      GRADE were used to evaluate the overall quality of the evidence and to develop
      recommendations. Eight studies were included. There was "very low" quality
      evidence for comparing a liberalised and restricted fibre diet for inpatient
      management to improve hospital length of stay, recovery, gastrointestinal
      symptoms and reoccurrence. There was "very low" quality of evidence for using a
      high dietary fibre diet as opposed to a standard or low dietary fibre diet
      following resolution of an acute episode, to improve reoccurrence and
      gastrointestinal symptoms. The results of this systematic review and GRADE
      assessment conditionally recommend the use of liberalised diets as opposed to
      dietary restrictions for adults with acute, uncomplicated diverticulitis. It also
      strongly recommends a high dietary fibre diet aligning with dietary guidelines,
      with or without dietary fibre supplementation, after the acute episode has
      resolved.

PMID- 29382076
TI  - Fungi as Endophytes in Artemisia thuscula: Juxtaposed Elements of Diversity and
      Phylogeny.
AB  - Artemisia is a plant genus highly studied for its medicinal applications. The
      studies on the associated fungal endophytes are scarce. Ten plants specimens of
      Artemisia thuscula from Tenerife and La Palma were sampled to isolate the
      endophytic fungi. Identification of the endophytic fungi was based on morphology,
      Internal Transcribed Spacer (ITS) and Large Subunit (LSU) regions sequencing and
      indicates 37 fungal species affiliated to 25 fungal genera. Colonization rate
      varied among plants (CR = 25% to 92.11%). The most dominant colonizers found were
      Alternaria alternata (CF = 18.71%), Neofusicoccum sp. (CF = 8.39%) and Preussia
      sp. (CF = 3.23). Tendency for host specificity of most endophytic fungal species
      was observed. Sorensen-Dice index revealed that of 45 cases in the matrix, 27 of
      them were of zero similarity. Further, only one case was found to have 57%
      similarity (TF2 and TF7) and one case with 50% similarity (TF1 and TF4). The rest
      of the cases had values ranging between 11% and 40% similarity. Diversity indices
      like Brillouin, Margalef species richness, Simpson index of diversity and
      Fisher's alpha, revealed plants from La Palma with higher values than plants from
      Tenerife. Three nutrient media (i.e., potato dextrose agar-PDA, lignocellulose
      agar-LCA, and tomato juice agar-V8) were used in a case study and revealed no
      differences in terms of colonization rate when data was averaged. Colonization
      frequency showed several species with preference for nutrient medium (63% of the
      species were isolated from only one nutrient medium). For the phylogenetic
      reconstruction using the Bayesian method, 54 endophytic fungal ITS sequences and
      associated GenBank sequences were analyzed. Ten orders (Diaporthales,
      Dothideales, Botryosphaeriales, Hypocreales, Trichosphaeriales, Amphisphaeriales,
      Xylariales, Capnodiales, Pleosporales and Eurotiales) were recognized. Several
      arrangements of genera draw the attention, like Aureobasidium (Dothideales) and
      Aplosporella (Botryosphaeriales) which are clustered with a recent ancestor (BS =
      0.97).

PMID- 29382075
TI  - Systematic Structure-Activity Relationship (SAR) Exploration of Diarylmethane
      Backbone and Discovery of A Highly Potent Novel Uric Acid Transporter 1 (URAT1)
      Inhibitor.
AB  - In order to systematically explore and better understand the structure-activity
      relationship (SAR) of a diarylmethane backbone in the design of potent uric acid
      transporter 1 (URAT1) inhibitors, 33 compounds (1a-1x and 1ha-1hi) were designed
      and synthesized, and their in vitro URAT1 inhibitory activities (IC50) were
      determined. The three-round systematic SAR exploration led to the discovery of a
      highly potent novel URAT1 inhibitor, 1h, which was 200- and 8-fold more potent
      than parent lesinurad and benzbromarone, respectively (IC50 = 0.035 MUM against
      human URAT1 for 1h vs. 7.18 MUM and 0.28 MUM for lesinurad and benzbromarone,
      respectively). Compound 1h is the most potent URAT1 inhibitor discovered in our
      laboratories so far and also comparable to the most potent ones currently under
      development in clinical trials. The present study demonstrates that the
      diarylmethane backbone represents a very promising molecular scaffold for the
      design of potent URAT1 inhibitors.

PMID- 29382077
TI  - VEGF Triggers the Activation of Cofilin and the Arp2/3 Complex within the Growth
      Cone.
AB  - A crucial neuronal structure for the development and regeneration of neuronal
      networks is the axonal growth cone. Affected by different guidance cues, it grows
      in a predetermined direction to reach its final destination. One of those cues is
      the vascular endothelial growth factor (VEGF), which was identified as a positive
      effector for growth cone movement. These positive effects are mainly mediated by
      a reorganization of the actin network. This study shows that VEGF triggers a
      tight colocalization of cofilin and the Arp2/3 complex to the actin cytoskeleton
      within chicken dorsal root ganglia (DRG). Live cell imaging after microinjection
      of GFP (green fluorescent protein)-cofilin and RFP (red fluorescent protein)
      LifeAct revealed that both labeled proteins rapidly redistributed within growth
      cones, and showed a congruent distribution pattern after VEGF supplementation.
      Disruption of signaling upstream of cofilin via blocking LIM-kinase (LIMK)
      activity resulted in growth cones displaying regressive growth behavior.
      Microinjection of GFP-p16b (a subunit of the Arp2/3 complex) and RFP-LifeAct
      revealed that both proteins redistributed into lamellipodia of the growth cone
      within minutes after VEGF stimulation. Disruption of the signaling to the Arp2/3
      complex in the presence of VEGF by inhibition of N-WASP (neuronal Wiskott-Aldrich
      Scott protein) caused retraction of growth cones. Hence, cofilin and the Arp2/3
      complex appear to be downstream effector proteins of VEGF signaling to the actin
      cytoskeleton of DRG growth cones. Our data suggest that VEGF simultaneously
      affects different pathways for signaling to the actin cytoskeleton, since
      activation of cofilin occurs via inhibition of LIMK, whereas activation of Arp2/3
      is achieved by stimulation of N-WASP.

PMID- 29382078
TI  - Vehicle Detection with Occlusion Handling, Tracking, and OC-SVM Classification: A
      High Performance Vision-Based System.
AB  - This paper presents a high performance vision-based system with a single static
      camera for traffic surveillance, for moving vehicle detection with occlusion
      handling, tracking, counting, and One Class Support Vector Machine (OC-SVM)
      classification. In this approach, moving objects are first segmented from the
      background using the adaptive Gaussian Mixture Model (GMM). After that, several
      geometric features are extracted, such as vehicle area, height, width, centroid,
      and bounding box. As occlusion is present, an algorithm was implemented to reduce
      it. The tracking is performed with adaptive Kalman filter. Finally, the selected
      geometric features: estimated area, height, and width are used by different
      classifiers in order to sort vehicles into three classes: small, midsize, and
      large. Extensive experimental results in eight real traffic videos with more than
      4000 ground truth vehicles have shown that the improved system can run in real
      time under an occlusion index of 0.312 and classify vehicles with a global
      detection rate or recall, precision, and F-measure of up to 98.190%, and an F
      measure of up to 99.051% for midsize vehicles.

PMID- 29382079
TI  - A Simple Method to Reduce both Lactic Acid and Ammonium Production in Industrial
      Animal Cell Culture.
AB  - Fed-batch animal cell culture is the most common method for commercial production
      of recombinant proteins. However, higher cell densities in these platforms are
      still limited due to factors such as excessive ammonium production, lactic acid
      production, nutrient limitation, and/or hyperosmotic stress related to nutrient
      feeds and base additions to control pH. To partly overcome these factors, we
      investigated a simple method to reduce both ammonium and lactic acid production
      termed Lactate Supplementation and Adaptation (LSA) technology-through the use of
      CHO cells adapted to a lactate-supplemented medium. Using this simple method, we
      achieved a reduction of nearly 100% in lactic acid production with a simultaneous
      50% reduction in ammonium production in batch shaker flasks cultures. In
      subsequent fed-batch bioreactor cultures, lactic acid production and base
      addition were both reduced eight-fold. Viable cell densities of 35 million cells
      per mL and integral viable cell days of 273 million cell-days per mL were
      achieved, both among the highest currently reported for a fed-batch animal cell
      culture. Investigating the benefits of LSA technology in animal cell culture is
      worthy of further consideration and may lead to process conditions more favorable
      for advanced industrial applications.

PMID- 29382080
TI  - Structural Studies of Predicted Ligand Binding Sites and Molecular Docking
      Analysis of Slc2a4 as a Therapeutic Target for the Treatment of Cancer.
AB  - Presently, many studies have focused on exploring in silico approaches in the
      identification and development of alternative therapy for the treatment and
      management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which
      encodes glucose transporter 4 protein (GLUT4), has been identified as a promising
      therapeutic target for cancer. Though Slc2a4 is known to play a major regulatory
      role in the pathophysiology of type 2 diabetes, emerging evidence suggests that
      successful pharmacological inhibition of this protein may lead to the development
      of a novel drug candidate for the treatment of cancer. In this study, Slc2a4
      protein sequence was retrieved and analysed using in silico approaches, and we
      identified seven putative antimicrobial peptides (AMPs; RAB1-RAB7) as anti
      cancer. The structures of the protein and AMPs were modelled using I-TASSER
      server, and the overall quality of the Slc2a4 model was validated using PROCHECK.
      Subsequently, the probable motifs and active site of the protein were forecasted.
      Also, the molecular interaction between the AMPs and Slc2a4 was ascertained using
      PatchDock. The result revealed that, all the AMPs are good Slc2a4 inhibitors with
      RAB1 having the highest binding affinity of 12,392 and binding energy of -39.13
      kcal/mol. Hence, this study reveals that all the generated AMPs can serve as
      therapeutic drug in treating cancer by inhibiting Slc2a4 which is responsible for
      the production of energy for cancer cells during angiogenesis. This is the first
      report on AMPs as inhibitors of Slc2a4 for the treatment of cancer.

PMID- 29382081
TI  - N-Salicyloyltryptamine, an N-Benzoyltryptamine Analogue, Induces Vasorelaxation
      through Activation of the NO/sGC Pathway and Reduction of Calcium Influx.
AB  - Benzoyltryptamine analogues act as neuroprotective and spasmolytic agents on
      smooth muscles. In this study, we investigated the ability of N
      salicyloyltryptamine (STP) to produce vasorelaxation and determined its
      underlying mechanisms of action. Isolated rat mesenteric arteries with and
      without functional endothelium were studied in an isometric contraction system in
      the presence or absence of pharmacological inhibitors. Amperometric experiments
      were used to measure the nitric oxide (NO) levels in CD31+ cells using flow
      cytometry. GH3 cells were used to measure Ca2+ currents using the whole cell
      patch clamp technique. STP caused endothelium-dependent and -independent
      relaxation in mesenteric rings. The endothelial-dependent relaxations in response
      to STP were markedly reduced by L-NAME (endothelial NO synthase-eNOS-inhibitor),
      jHydroxocobalamin (NO scavenger, 30 uM) and ODQ (soluble Guanylyl Cyclase-sGC
      inhibitor, 10 uM), but were not affected by the inhibition of the formation of
      vasoactive prostanoids. These results were reinforced by the increased NO levels
      observed in the amperometric experiments with freshly dispersed CD31+ cells. The
      endothelium-independent effect appeared to involve the inhibition of voltage
      gated Ca2+ channels, due to the inhibition of the concentration-response Ca2+
      curves in depolarizing solution, the increased relaxation in rings that were pre
      incubated with high extracellular KCl (80 mM), and the inhibition of macroscopic
      Ca2+ currents. The present findings show that the activation of the NO/sGC/cGMP
      pathway and the inhibition of gated-voltage Ca2+ channels are the mechanisms
      underlying the effect of STP on mesenteric arteries.

PMID- 29382082
TI  - Validation of the English Version of the 14-Item Mediterranean Diet Adherence
      Screener of the PREDIMED Study, in People at High Cardiovascular Risk in the UK.
AB  - The aim of this study was to examine the validity of the English version of the
      PREvencion con DIetaMEDiterranea (PREDIMED) 14-item Mediterranean Diet Adherence
      Screener (MEDAS), a brief questionnaire assessing adherence to the Mediterranean
      diet (MedDiet), which was used in the PREDIMED trial for assessment and immediate
      feedback. This instrument (MEDAS) was administered to 96 adults with a high
      cardiovascular risk (66% women, mean age 68.3 +/- 6.0 years), recruited from
      general practices in Bristol, UK. Participants then completed a 3-day estimated
      food record, and the MEDAS was administered again one month later. A MedDiet
      score (range = 0-14) was calculated from the MEDAS' administrations and food
      record to assess concurrent validity and test-retest reliability. Predictive
      validity was assessed by examining the association of the MEDAS-derived score
      with cardiometabolic risk factors and dietary intakes derived from the food
      records. The MEDAS-derived MedDiet score was higher by 1.47 points compared to
      food records (5.47 vs.4.00, p < 0.001), correlated moderately with the record
      derived score (r = 0.50, p < 0.001; ICC = 0.53, p < 0.001) and there was
      borderline fair agreement between the two methods (kappa = 0.19, 95% CI 0.07
      0.31, p = 0.002; 95% limits of agreement -2.2, 5.1). Exact agreement within score
      categories and gross misclassificationwere 45.8% and 21.9%, respectively. The
      distribution of dietary intakes, reported on the food records by the MEDAS
      derived total MedDiet score, was in the expected direction, but no association
      was observed with cardiometabolic risk factors. The two administrations of the
      MEDAS produced similar mean total MedDiet scores (5.5 vs. 5.4, p = 0.706), which
      were correlated (r and ICC = 0.69, p < 0.001) and agreed fairly (kappa = 0.38,
      95% CI 0.24-0.52, p < 0.001; 95% limits of agreement -3.1, 3.2). The English
      version of the MEDAS has acceptable accuracy and reliability for assessing
      MedDiet adherence among individuals with a high cardiovascular risk, in the UK,
      and can be used to rank individuals according to MedDiet adherence in research
      and practice.